PMID- 29707192
TI  - Evaluation of hearing level in patients on long term aspirin therapy.
AB  - Introduction: Aspirin is a routinely prescribed drug, most notably for
      cardiovascular diseases, such as myocardial ischemia. This cross sectional,
      comparative study study aims to explore differences in hearing status between the
      cardiovascular disease patients on aspirin therapy and age matched controls.
      Methods: The study population consisted of 182 patients with heart disease taking
      long term aspirin (i.e., for more than one year). The control population
      consisted of 221 age matched controls who were not taking aspirin. Results: It
      was found that age of patient, not aspirin intake, was more important risk factor
      contributing to hearing loss.  Conclusions: When confounding factors like age of
      the patient, hypertension and diabetes were taken into account, aspirin in its
      antiplatelet dose was not found to be the cause of any audiological problems like
      tinnitus and hearing loss.

PMID- 29707193
TI  - What do we know about grant peer review in the health sciences?
AB  - Background: Peer review decisions award an estimated >95% of academic medical
      research funding, so it is crucial to understand how well they work and if they
      could be improved. Methods: This paper summarises evidence from 105 papers
      identified through a literature search on the effectiveness and burden of peer
      review for grant funding. Results: There is a remarkable paucity of evidence
      about the efficiency of peer review for funding allocation, given its centrality
      to the modern system of science. From the available evidence, we can identify
      some conclusions around the effectiveness and burden of peer review. The
      strongest evidence around effectiveness indicates a bias against innovative
      research. There is also fairly clear evidence that peer review is, at best, a
      weak predictor of future research performance, and that ratings vary considerably
      between reviewers. There is some evidence of age bias and cronyism. Good evidence
      shows that the burden of peer review is high and that around 75% of it falls on
      applicants. By contrast, many of the efforts to reduce burden are focused on
      funders and reviewers/panel members. Conclusions: We suggest funders should
      acknowledge, assess and analyse the uncertainty around peer review, even using
      reviewers' uncertainty as an input to funding decisions. Funders could consider a
      lottery element in some parts of their funding allocation process, to reduce both
      burden and bias, and allow better evaluation of decision processes.
      Alternatively, the distribution of scores from different reviewers could be
      better utilised as a possible way to identify novel, innovative research. Above
      all, there is a need for open, transparent experimentation and evaluation of
      different ways to fund research. This also requires more openness across the
      wider scientific community to support such investigations, acknowledging the lack
      of evidence about the primacy of the current system and the impossibility of
      achieving perfection.

PMID- 29707194
TI  - Rapid coral mortality following unusually calm and hot conditions on Iriomote,
      Japan.
AB  - Coral bleaching can be induced by many different stressors, however, the most
      common cause of mass bleaching in the field is higher than average sea surface
      temperatures (SST). Here, we describe an unusual bleaching event that followed
      very calm sea conditions combined with higher than average SST. Patterns of
      mortality differed from typical bleaching in four ways: 1) mortality was very
      rapid; 2) a different suite of species were most affected; 3) tissue mortality in
      Acropora spp. was often restricted to the center of the colony; 4) the event
      occurred early in summer. The two weeks prior to the event included 8 days where
      the average wind speed was less than 3 ms -1. In addition, SSTs in the weeks
      preceding and during the event were 1.0-1.5 degrees C higher than the mean for
      the last 30 years. We hypothesize that this unusual bleaching event was caused by
      anoxia resulting from a lack of water movement induced by low wind speeds
      combined with high SST.

PMID- 29707195
TI  - Case Report: A rare case of prosthetic valve infective endocarditis caused by
      Aerococcus urinae.
AB  - Infective endocarditis (IE) is a serious and life-threatening cardiac condition,
      most commonly caused by staphylococci, Streptococcus viridans, and enterococci.
      However, in special settings, IE can be caused by rare organisms. Here we present
      a case of IE caused by Aerococcus urinae in a 75-year-old man with a
      bioprosthetic aortic valve.  Aerococcusurinae is a gram-positive, catalase
      negative microorganism and is usually an isolate of complicated urinary tract
      infections in the elderly male population.  . Improvements in diagnostic testing
      including use of matrix-assisted laser desorption ionization- a time of flight
      mass spectrometry (MALDI-TOF MS) have played an important role in isolating
      Aerococcus.

PMID- 29707195
TI  - Case Report: A rare case of prosthetic valve infective endocarditis caused by
      Aerococcus urinae.
AB  - Infective endocarditis (IE) is a serious and life-threatening cardiac condition,
      most commonly caused by staphylococci, Streptococcus viridans, and enterococci.
      However, in special settings, IE can be caused by rare organisms. Here we present
      a case of IE caused by Aerococcus urinae in a 75-year-old man with a
      bioprosthetic aortic valve.  Aerococcusurinae is a gram-positive, catalase
      negative microorganism and is usually an isolate of complicated urinary tract
      infections in the elderly male population.  Improvements in diagnostic testing
      including use of matrix-assisted laser desorption ionization- a time of flight
      mass spectrometry (MALDI-TOF MS) have played an important role in recognition of
      Aerococcus urinae.

PMID- 29707197
TI  - Case Report: Clinically amyopathic dermatomyositis presenting acutely with
      isolated facial edema.
AB  - A 45-year-old Asian man presented with acute-onset periorbital and facial edema
      associated with pyrexia. Muscle weakness was absent. Initial laboratory
      investigations showed an inflammatory reaction, while screening for infections
      was negative. Serum muscle enzyme levels were normal. He was hospitalized and
      treated empirically with antibiotics and corticosteroids, pending the result of
      facial skin and muscle biopsy. He showed a good clinical and laboratory response
      but an attempt to discontinue corticosteroids led to a prompt relapse of facial
      edema and pyrexia, associated with rising laboratory indices of inflammation.
      Biopsy findings were typical of dermatomyositis. Reintroduction of corticosteroid
      treatment resulted in complete clinical and laboratory remission. Facial edema as
      the sole clinical manifestation of dermatomyositis is extremely rare. There have
      been no previous reports of isolated facial edema in the setting of acute,
      clinically amyopathic dermatomyositis in adults. A high level of suspicion is
      required to make the diagnosis in the absence of myopathy and the hallmark
      cutaneous manifestations of the disease (heliotrope rash, Gottron papules).

PMID- 29707198
TI  - Spatial band-pass filtering aids decoding musical genres from auditory cortex 7T
      fMRI.
AB  - Spatial filtering strategies, combined with multivariate decoding analysis of
      BOLD images, have been used to investigate the nature of the neural signal
      underlying the discriminability of brain activity patterns evoked by sensory
      stimulation - primarily in the visual cortex. Previous research indicates that
      such signals are spatially broadband in nature, and are not primarily comprised
      of fine-grained activation patterns. However, it is unclear whether this is a
      general property of the BOLD signal, or whether it is specific to the details of
      employed analyses and stimuli. Here we applied an analysis strategy from a
      previous study on decoding visual orientation from V1 to publicly available, high
      resolution 7T fMRI on the response BOLD response to musical genres in primary
      auditory cortex. The results show that the pattern of decoding accuracies with
      respect to different types and levels of spatial filtering is comparable to that
      obtained from V1, despite considerable differences in the respective cortical
      circuitry.

PMID- 30090624
TI  - Role of B-cell receptors for B-cell development and antigen-induced
      differentiation.
AB  - B-cell development is characterized by a number of tightly regulated selection
      processes. Signals through the B-cell receptor (BCR) guide and are required for B
      cell maturation, survival, and fate decision. Here, we review the role of the BCR
      during B-cell development, leading to the emergence of B1, marginal zone, and
      peripheral follicular B cells. Furthermore, we discuss BCR-derived signals on
      activated B cells that lead to germinal center and plasma cell differentiation.

PMID- 30090625
TI  - An overview of gambling disorder: from treatment approaches to risk factors.
AB  - Gambling disorder (GD) has been reclassified recently into the "Substance-Related
      and Addictive Disorders" category of the Diagnostic and Statistical Manual of
      Mental Disorders, Fifth Edition (DSM-5), a landmark occurrence for a behavioral
      addiction. GD is characterized by recurrent, maladaptive gambling behavior that
      results in clinically significant distress. Although the number of randomized
      controlled trials assessing the effectiveness of pharmacological treatments is
      limited, some pharmacological treatments, notably opiate antagonists, have been
      employed in the treatment of GD. Patients with GD often present cognitive
      distortions and specific personality traits, making treatment more difficult.
      Cognitive behavioral therapy has become the most common psychological
      intervention for treating gambling problems, and it is effective in reducing
      gambling behavior. In this brief overview, we provide a report on the state of
      pharmacological and psychological treatments for gambling disorder. Risk factors
      and potential future lines of research are addressed.

PMID- 30090626
TI  - Recent advances in the understanding and management of underactive bladder.
AB  - Underactive bladder (UAB) is an important and complex urological condition
      resulting from the urodynamic finding of detrusor underactivity. It can manifest
      in a wide range of lower urinary tract symptoms, from voiding to storage
      complaints, and can overlap with other conditions, including overactive bladder
      and bladder outlet obstruction. However, UAB continues to be poorly understood
      and inadequately researched. In this article, we review the contemporary
      literature pertaining to recent advances in defining, understanding, and managing
      UAB.

PMID- 30090627
TI  - The ERA-EDTA today and tomorrow: a progress document by the ERA-EDTA Council.
AB  - Scientific societies are increasingly seen as central to the advancement of
      information sharing and collaboration among scientists and clinical investigators
      for the progress of medical research and the promotion of education, professional
      competence, integrity and quality studies. To more effectively serve the
      practicing nephrologists and investigators dedicated to renal science, the
      Council of the European Renal Association and European Dialysis and
      Transplantation Association (ERA-EDTA) reorganized and integrated the various
      activities of the society into two branches, the Clinical Nephrology Governance
      branch and the Renal Science branch. New affordable initiatives to promote
      research, education and professional development and to advocate for the
      recognition of chronic kidney disease as a major public health issue at the
      European level will be put in place and/or potentiated in the new organizational
      frame. Educational initiatives will be espoused to Continuous Professional
      Development and, starting from 2019, 14 Education & Continuous Professional
      Development courses will be held covering the full range of knowledge areas of
      modern nephrology. Consolidation and development is the short- and medium-term
      mantra of the ERA-EDTA. The society has a rich portfolio of successful activities
      and brilliant, creative scientists among its members. Integrating the various
      activities of the ERA-EDTA and treasuring the expertise and wisdom of its most
      accomplished members will facilitate collaborative research, education and its
      public impact at large.

PMID- 30090628
TI  - Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1.
AB  - Little is known about the molecular pathogenesis of congenital nephrotic syndrome
      in association with primary adrenal insufficiency. Most recently, three groups
      found concurrently the underlying genetic defect in the gene sphingosine-1
      phosphate lyase 1 (SGPL1) and called the disease nephrotic syndrome type 14
      (NPHS14). In this report we have performed whole-exome sequencing and identified
      a new homozygous variant in SGPL1, p.Arg340Trp, in a girl with nephrotic syndrome
      and Addison's disease. Her brother died previously with the same phenotype and
      hyperpigmentation of the skin. We reviewed the reported cases and concluded that
      NPHS14 is a clinically recognizable syndrome. The discovery of this syndrome may
      contribute to the diagnosis and description of additional patients who could
      benefit from treatment, genetic counseling and screening for related
      comorbidities. Until now, patients with congenital nephrotic syndrome associated
      with primary adrenal insufficiency have been treated as having two different
      diseases; however, the treatment for patients with NPHS14 should be unique,
      possibly targeting the sphingolipid metabolism.

PMID- 30090629
TI  - Hand grip strength measurement in haemodialysis patients: before or after the
      session?
AB  - Background: Hand grip strength (HGS) is a key measurement in the assessment of
      frailty phenotype in haemodialysis patients. However, the measurement is not very
      standardized, and notably, current data on the potential impact of a
      haemodialysis session on the results are both limited and controversial. In the
      present analysis, we compared HGS results before and after a haemodialysis
      session in 101 patients. Methods: In the current observational study, HGS has
      been measured in adult haemodialysis patients on the same day, first before
      connection to the dialysis machine and then just after disconnection. At each
      timing, measurements were repeated three times with an interval of 5 s between
      measurements and the higher value was used for analysis. Results: One hundred and
      one patients (64% men) with a median (interquartile range, 25th percentile; 75th
      percentile) age of 66 (46; 76) years were included. In the whole population, a
      significant decline in HGS was observed after dialysis, with an absolute median
      decline of - 4 (0; -6) kg and a relative median difference of -11 (0; -20)%.
      These differences were observed in both genders and were independent of the
      baseline HGS value. Conclusions: Our results suggest that the timing (before or
      after the dialysis session) of hand grip assessment is clinically relevant and
      should be taken into account in clinical practice and also in epidemiological and
      clinical studies.

PMID- 30090630
TI  - Genetic susceptibility to delayed graft function following kidney
      transplantation: a systematic review of the literature.
AB  - Delayed graft function (DGF) is defined as the need for dialysis within 7 days
      following kidney transplantation (KTx). DGF is associated with increased costs,
      higher risk for acute rejection and decreased long-term graft function. Renal
      ischaemia/reperfusion (I/R) injury plays a major role in DGF occurrence. Single
      nucleotide polymorphisms (SNPs) in certain genes may aggravate kidney
      susceptibility to I/R injury, thereby worsening post-transplant outcomes. The
      present article proposes an extensive review of the literature about the putative
      impact of donor or recipient SNPs on DGF occurrence in kidney transplant
      recipients (KTRs). Among 30 relevant PubMed reports, 16 articles identified an
      association between 18 SNPs and DGF. These polymorphisms concern 14 different
      well-known genes and one not-yet-identified gene located on chromosome 18. They
      have been categorized into five groups according to the role of the corresponding
      proteins in I/R cascade: (i) oxidative stress, (ii) telomere shortening, (iii)
      chemokines, (iv) T-cell homeostasis and (v) metabolism of anti-inflammatory
      molecules. The remaining 14 studies failed to demonstrate any association between
      the studied SNPs and the occurrence of DGF. A better understanding of the genetic
      susceptibility to renal I/R injury may help prevent DGF and improve clinical
      outcomes in KTRs.

PMID- 30090631
TI  - Do sexually transmitted infections exacerbate negative premenstrual symptoms?
      Insights from digital health.
AB  - Background and objectives: The underlying reasons why some women experience
      debilitating premenstrual symptoms and others do not are largely unknown. Here,
      we test the evolutionary ecological hypothesis that some negative premenstrual
      symptoms may be exacerbated by the presence of chronic sexually transmitted
      infections (STIs). Methodology: 34 511 women were recruited through a digital
      period-tracker app. Participants were asked: (i) Have you ever been diagnosed
      with a STI? (ii) If yes, when was it, and were you given treatment? Those data
      were combined with longitudinal cycle data on menstrual bleeding patterns, the
      experience of pain and emotions and hormonal contraceptive use. Results: 865
      women had at least two complete menstrual cycle data and were eligible for
      analysis. Before diagnosis, the presence of an infection predicts a ca. 2-fold
      increase in the odds of reporting both headache, cramps and sadness during the
      late luteal phase and sensitive emotions during the wider luteal phase. After
      diagnosis, the odds of reporting negative symptoms pre-menstrually remain
      unchanged among STI negative individuals, but the odds of reporting sensitive
      emotions decrease among STI positive individuals receiving a treatment. No
      relationships between STIs, pain and emotions are observed among hormonal
      contraceptive users. Conclusions and implications: The results support the idea
      that a negative premenstrual experience might be aggravated by the presence of
      undiagnosed STIs, a leading cause of infertility worldwide. Caution is warranted
      in extrapolating the results as the data are self-reported, inflammatory levels
      are unknown and the tracker is biased towards recording negative premenstrual
      symptoms among Western individuals.

PMID- 30090632
TI  - Genomics helps to decipher the resistance mechanisms present in a Pseudomonas
      chlororaphis strain recovered in an HIV patient.

PMID- 30090633
TI  - New species announcement 2.1.

PMID- 30090634
TI  - Enterobacter cloacae harbouring blaKPC-2 and qnrB-1 isolated from a cystic
      fibrosis patient: a case report.
AB  - We describe the first detection of a KPC-2- and QnrB-producing Enterobacter
      cloacae from a patient with cystic fibrosis. The blaKPC-2 and qnrB-1 genes were
      located in a 79.8-kb plasmid. The presence of blaKPC-2 and qnrB-1 genes was
      determined by PCR and sequencing. Mobilization of plasmid containing blaKPC2 gene
      was assayed by conjugation.

PMID- 30090635
TI  - Guillain-Barre syndrome hyponatremia: is it SIADH or pseudohyponatremia?
AB  - Approximately 5% of hospitalized patients with Guillain-Barre syndrome (GBS)
      experience SIADH; but pseudohyponatremia has also been reported in patients
      treated with IVIG. We present a case of a 51-year-old male with GBS who developed
      acute hyponatremia the day after initiation of IVIG; his sodium levels began to
      improve within 24 h of completion of IVIG. Differentiating between
      pseudohyponatremia caused by the IVIG treatment and SIADH caused by GBS was the
      key to successfully treating this patient. This case exemplifies the importance
      of pursuing further studies to determine the exact cause of hyponatremia in GBS
      in order to prevent further neurologic damage to the patient.

PMID- 30090636
TI  - Feline gastric pneumatosis.
AB  - Case summary: A 9-year-old male neutered domestic shorthair cat was presented
      with a 2 day history of anorexia and vomiting. A minimum database, including a
      complete blood count, serum biochemistry profile and urinalysis were unremarkable
      apart from a toxic neutrophilic left shift and borderline proteinuria. Abdominal
      ultrasound revealed intramural gas entrapment with thinning of the gastric wall,
      a hypoechoic pancreas, peritoneal fluid and a small volume of peritoneal gas
      along with a hyperechoic mesentery. CT was performed and demonstrated gas within
      the gastric submucosa and gas in the peritoneal cavity. Generalised gastric
      erythema was present at surgery and histopathology of excised abnormal areas
      reported gastric erosion with no obvious causative agents; however, pretreatment
      with dexamethasone may have been a contributing factor. Culture from biopsied
      gastric tissue was sterile. Clinical signs resolved after partial gastrectomy and
      medical management. Relevance and novel information: Feline gastric pneumatosis
      is a rare clinical finding. Imaging is essential for diagnosis and to decide on
      the appropriate treatment; this is often medical but in cases where there is
      suspicion or evidence of gastric perforation, surgery is indicated. To our
      knowledge, this is the first case of feline gastric pneumatosis secondary to
      gastric ulceration, diagnosed via CT and where dexamethasone may have been a
      contributing factor.

PMID- 30090637
TI  - Onset of secondary progressive multiple sclerosis is not influenced by current
      relapsing multiple sclerosis therapies.
AB  - Background: Disease-modifying therapies are thought to reduce the conversion rate
      to secondary progressive multiple sclerosis. Objective: To explore the rate,
      chronology, and contributing factors of conversion to the progressive phase in
      treated relapsing-remitting multiple sclerosis patients. Methods: Our study
      included 204 patients treated for relapsing-remitting multiple sclerosis between
      1995 and 2002, prospectively followed to date. Kaplan-Meier analysis was applied
      to estimate the time until secondary progressive multiple sclerosis conversion,
      and multivariate survival analysis with a Cox regression model was used to
      analyse prognostic factors. Results: Relapsing-remitting multiple sclerosis
      patients were continuously treated for 13 years (SD 4.5); 36.3% converted to
      secondary progressive multiple sclerosis at a mean age of 42.6 years (SD 10.6), a
      mean time of 8.2 years (SD 5.2) and an estimated mean time of 17.2 years (range
      17.1-18.1). A multifocal relapse, age older than 34 years at disease onset and
      treatment failure independently predicted conversion to secondary progressive
      multiple sclerosis but did not influence the time to reach an Expanded Disability
      Status Scale of 6.0. Conclusions: The favourable influence of disease-modifying
      therapies on long-term disability in relapsing-remitting multiple sclerosis is
      well established. However, the time to progression onset and the subsequent
      clinical course in treated patients seem similar to those previously reported in
      natural history studies. More studies are needed to clarify the effect of disease
      modifying therapies once the progressive phase has been reached.

PMID- 30090638
TI  - Development of a gait module to complement the 12-item Multiple Sclerosis Walking
      Scale: a mixed methods study.
AB  - Background and objective: The 12-item Multiple Sclerosis Walking Scale (MSWS-12)
      is a patient-reported outcome instrument that quantifies the progressive loss of
      walking ability from the patient perspective. However, previous psychometric
      analyses indicated floor and ceiling effects across the multiple sclerosis
      severity spectrum. This study aimed to address floor effects by creating a gait
      module that can be used in conjunction with the MSWS-12 for better measurement of
      treatment benefit in the higher functioning multiple sclerosis population.
      Methods: We used a step-wise mixed methods study design, with relapsing-remitting
      multiple sclerosis patients (wave 1, n=88; wave 2, n=30), combining qualitative
      (concept elicitation and cognitive debriefing interviews) and quantitative (Rasch
      Measurement Theory) data collection and analytical techniques and consultation
      interviews with three neurologists specializing in multiple sclerosis. Results:
      Thirty-seven walking ability concepts were identified, and a five-domain
      conceptual framework was created. Draft items were generated and refined with
      patient and neurologist input. Draft items covered gait-related concepts such as
      dragging, shuffling, limping, tripping and falling. Rasch measurement theory
      psychometric analysis indicated administering MSWS-12 plus gait items improved
      measurement precision in targeted populations with better walking ability.
      Conclusion: Study findings indicate that new gait items could improve sensitivity
      to detect clinical change in walking ability for higher functioning multiple
      sclerosis patients.

PMID- 30090639
TI  - Cladribine: Off-label disease modification for people with multiple sclerosis in
      resource-poor settings?
AB  - Background: A considerable number of people with multiple sclerosis (pwMS) live
      in low- and middle-income countries (LMIC), where lack of resource adversely
      affects access to effective disease-modifying treatment. Objective: The objective
      of this commentary is to propose a useful cost-effective disease-modifying
      treatment option for pwMS in LMIC with potential high efficacy and high
      convenience to the pwMS and treating physician.Viewpoint: We propose using
      generic 2-chloro-2'-deoxyadenosine (cladribine), a small molecule licensed for
      treatment of people with hairy cell leukaemia, as a solution of this significant
      equity imbalance. Cladribine has been shown in phase II and III trials to be a
      highly effective disease-modifying treatment for pwMS, and its adverse effect
      profile is comparable with any DMT currently licensed in high-income economies
      where an oral preparation has recently been licensed by the European Medicines
      Agency. Conclusion: Our viewpoint takes into account experience we have gathered
      over the past three years in the use of generic cladribine to treat pwMS. Whilst
      here we focus on MS, there is significant potential for use of cladribine in
      other conditions that could benefit from its mechanism of action.

PMID- 30090640
TI  - Costs and quality of life by disability among people with multiple sclerosis: a
      register-based study in Sweden.
AB  - Background: Population-based estimates of costs of illness and health-related
      quality of life, by disability levels among people with multiple sclerosis, are
      lacking. Objectives: To estimate the annual costs of illness and health-related
      quality of life, by disability levels, among multiple sclerosis patients, 21-64
      years of age. Methods: Microdata from Swedish nationwide registers were linked to
      estimate the prevalence-based costs of illness in 2013, including direct costs
      (prescription drug use and specialised healthcare) and indirect costs (calculated
      using sick leave and disability pension), and health-related quality of life
      (estimated from the EQ-5D). Disability level was measured by the Expanded
      Disability Status Scale (EDSS). Results: Among 8906 multiple sclerosis patients,
      EDSS 0.0-3.5 and 7.0-9.5 were associated with mean indirect costs of SEK 117,609
      and 461,357, respectively, whereas direct costs were similar between the
      categories (SEK 117,423 and 102,714, respectively). Prescription drug costs
      represented 40% of the costs of illness among multiple sclerosis patients with
      low EDSS, while among patients with high EDSS more than 80% were indirect costs.
      Among the 1684 individuals who had reported both EQ-5D and EDSS, the lowest
      health-related quality of life scores were found among those with a high EDSS.
      Conclusion: Among people with multiple sclerosis, we confirmed higher costs and
      lower health-related quality of life in higher disability levels, in particular
      high indirect costs.

PMID- 30090641
TI  - Objective and subjective measures of dalfampridine efficacy in clinical practice.
AB  - Background: Multiple sclerosis affects mobility in over 80% of patients.
      Dalfampridine is the only approved treatment for walking impairment in multiple
      sclerosis. We assessed dalfampridine utilization in our practice and investigated
      response using timed 25 foot walk (T25FW) improvement and a patient-reported
      ambulation inventory. Methods: Chart review identified patients with multiple
      sclerosis for whom dalfampridine was prescribed. T25FW data were extracted from
      medical records. Participants completed a dalfampridine-specific version of the
      multiple sclerosis walking scale (dMSWS-12) to assess the qualitative impact of
      dalfampridine on ambulation. We evaluated two responder categories: liberally
      defined as any improvement in T25FW; and over 20% T25FW improvement. Results: The
      dMSWS-12 questionnaire was completed by 39 patients. Eighteen patients (46%) did
      not show any T25FW improvement. Of the 21 patients (54%) with T25FW improvement,
      four patients (11%) showed improvement greater than 20%. Analysis of dMSWS-12
      scores showed a median score of 40 (range 12-60). Eleven patients (28%) showed no
      improvement (dMSWS-12 score <=36). In contrast to objective T25FW improvement
      (54%), 28 patients (72%) reported improvement in walking ability (dMSWS-12 score
      >=37). Conclusion: Our results suggest that T25FW alone might not be sufficient
      for response characterization and that adding patient-reported measures may
      further elucidate the therapeutic response.

PMID- 30090642
TI  - Promotion of physical activity and exercise in multiple sclerosis: Importance of
      behavioral science and theory.
AB  - There is an obvious disconnect between evidence of benefits and rates of
      participation in exercise and physical activity among people living with multiple
      sclerosis (MS). We propose that the problem with exercise behavior in MS (i.e.
      lack of broad or increasing participation by people with MS despite evidence of
      meaningful benefits) might be ameliorated through the inclusion of behavior
      change theory in the design of exercise programs and promotion efforts, as has
      been undertaken in other populations such as breast cancer survivors. This paper
      reviews Social Cognitive Theory as an example approach for informing
      interventions for increasing exercise and physical activity behavior outside of
      MS and provides an overview of current knowledge regarding the application of
      this theory for physical activity in MS. We then outline future research
      necessary for informing trials that design, implement, and test theory-based
      interventions for physical activity promotion in MS. If theories of behavior
      change are adopted for informing exercise and physical activity research in MS,
      we can take a major step forward in addressing the problem of exercise and
      physical activity participation that has plagued the field for more than 25
      years.

PMID- 30090643
TI  - Transgenerational epigenetic inheritance and social responsibility: perspectives
      from the social sciences.
AB  - Research in environmental epigenetics explores how environmental exposures and
      life experiences such as food, toxins, stress or trauma can shape trajectories of
      human health and well-being in complex ways. This perspective resonates with
      social science expertise on the significant health impacts of unequal living
      conditions and the profound influence of social life on bodies in general.
      Environmental epigenetics could thus provide an important opportunity for moving
      beyond long-standing debates about nature versus nurture between the disciplines
      and think instead in 'biosocial' terms across the disciplines. Yet, beyond
      enthusiasm for such novel interdisciplinary opportunities, it is crucial to also
      reflect on the scientific, social and political challenges that a biosocial model
      of body, health and illness might entail. In this paper, we contribute historical
      and social science perspectives on the political opportunities and challenges
      afforded by a biosocial conception of the body. We will specifically focus on
      what it means if biosocial plasticity is not only perceived to characterize the
      life of individuals but also as possibly giving rise to semi-stable traits that
      can be passed on to future generations. That is, we will consider the historical,
      social and political valences of the scientific proposition of transgenerational
      epigenetic inheritance. The key question that animates this article is if and how
      the notion of transgenerational epigenetic inheritance creates new forms of
      responsibilities both in science and in society. We propose that, ultimately,
      interdisciplinary conversation and collaboration is essential for responsible
      approaches to transgenerational epigenetic inheritance in science and society.

PMID- 30090644
TI  - Diesel exhaust and house dust mite allergen lead to common changes in the airway
      methylome and hydroxymethylome.
AB  - Exposures to diesel exhaust particles (DEP) from traffic and house dust mite
      (HDM) allergens significantly increase risks of airway diseases, including
      asthma. This negative impact of DEP and HDM may in part be mediated by epigenetic
      mechanisms. Beyond functioning as a mechanical barrier, airway epithelial cells
      provide the first line of immune defense towards DEP and HDM exposures. To
      understand the epigenetic responses of airway epithelial cells to these
      exposures, we exposed human bronchial epithelial cells to DEP and HDM and studied
      genome-wide 5-methyl-cytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) at base
      resolution. We found that exposures to DEP and HDM result in elevated TET1 and
      DNMT1 expression, associated with 5mC and 5hmC changes. Interestingly, over 20%
      of CpG sites are responsive to both exposures and changes in 5mC at these sites
      negatively correlated with gene expression differences. These 5mC and 5hmC
      changes are located in genes and pathways related to oxidative stress responses,
      epithelial function and immune cell responses and are enriched for binding sites
      of transcription factors (TFs) involved in these pathways. Histone marks
      associated with promoters, enhancers and actively transcribed gene bodies were
      associated with exposure-induced DNA methylation changes. Collectively, our data
      suggest that exposures to DEP and HDM alter 5mC and 5hmC levels at regulatory
      regions bound by TFs, which coordinate with histone marks to regulate gene
      networks of oxidative stress responses, epithelial function and immune cell
      responses. These observations provide novel insights into the epigenetic
      mechanisms that mediate the epithelial responses to DEP and HDM in airways.

PMID- 30090645
TI  - Blood glucose response after oral intake of lactulose in healthy volunteers: A
      randomized, controlled, cross-over study.
AB  - AIM: To investigate possible changes of blood glucose levels after oral intake of
      lactulose in healthy subjects. METHODS: The study was performed as prospective,
      randomized, two-part study with 4-way cross-over design with n = 12 in each study
      arm. Capillary blood glucose levels were determined over a time period of 180 min
      after intake of a single dose of 10 g or 20 g lactulose provided as crystal or
      liquid formulation. During the manufacturing process of lactulose, impurities
      with sugars (e.g., lactose, fructose, galactose) occur. Water and 20 g glucose
      were used as control and reference. Because lactulose is used as a functional
      food ingredient, it may also be consumed by people with impaired glucose
      tolerance, including diabetics. Therefore, it is of interest to determine whether
      the described carbohydrate impurities may increase blood glucose levels after
      ingestion. RESULTS: The blood glucose concentration-time curves after intake of
      10 g lactulose, 20 g lactulose, and water were almost identical. None of the
      three applications showed any changes in blood glucose levels. After intake of 20
      g glucose, blood glucose concentration increased by approximately 3 mmol/L (mean
      Cmax = 8.3 mmol/L), reaching maximum levels after approximately 30 min and
      returning to baseline within approximately 90 min, which was significantly
      different to the corresponding 20 g lactulose formulations (P < 0.0001).
      Comparing the two lactulose formulations, crystals and liquid, in the dosage of
      10 g and 20 g, there was no difference in the blood glucose profile and
      calculated pharmacokinetic parameters despite the different amounts of
      carbohydrate impurities (1.5% for crystals and 26.45% for liquid). Anyhow, the
      absolute amount of single sugars was low with 0.3 g in crystals and 5.29 g in
      liquid formulation in the 20 g dosages. Lactulose was well tolerated by most
      volunteers, and only some reported mild to moderate mainly gastrointestinal side
      effects. CONCLUSION: The unchanged blood glucose levels after lactulose intake in
      healthy subjects suggest its safe use in subjects with impaired glucose
      tolerance.

PMID- 30090646
TI  - The Role of Pulmonary and Systemic Immunosenescence in Acute Lung Injury.
AB  - Acute lung injury (ALI) is associated with increased morbidity and mortality in
      the elderly (> 65 years), but the knowledge about origin and effects of
      immunosenescence in ALI is limited. Here, we investigated the immune response at
      pulmonary, systemic and cellular level in young (2-3 months) and old (18-19
      months) C57BL/6J mice to localize and characterize effects of immunosenescence in
      ALI. ALI was induced by intranasal lipopolysaccharide (LPS) application and the
      animals were sacrificed 24 or 72 h later. Pulmonary inflammation was investigated
      by analyzing histopathology, bronchoalveolar lavage fluid (BALF) cytometry and
      cytokine expression. Systemic serum cytokine expression, spleen lymphocyte
      populations and the gut microbiome were analyzed, as well as activation of
      alveolar and bone marrow derived macrophages (BMDM) in vitro. Pulmonary pathology
      of ALI was more severe in old compared with young mice. Old mice showed
      significantly more inflammatory cells and pro-inflammatory cyto- or chemokines
      (TNFalpha, IL-6, MCP-1, CXCL1, MIP-1alpha) in the BALF, but a delayed expression
      of cytokines associated with activation of adaptive immunity and microbial
      elimination (IL-12 and IFNgamma). Alveolar macrophages, but not BMDM, of old mice
      showed greater activation after in vivo and in vitro stimulation with LPS. No
      systemic enhanced pro-inflammatory cytokine response was detected in old animals
      after LPS exposure, but a delayed expression of IL-12 and IFNgamma. Furthermore,
      old mice had less CD8+ T-cells and NK cells and more regulatory T-cells in the
      spleen compared with young mice and a distinct gut microbiome structure. The
      results of our study show an increased alveolar macrophage activation and pro
      inflammatory signaling in the lungs, but not systemically, suggesting a key role
      of senescent alveolar macrophages in ALI. A decrease in stimulators of adaptive
      immunity with advancing age might further promote the susceptibility to a worse
      prognosis in ALI in elderly.

PMID- 30090647
TI  - Effect of Aging and Glucagon-like Peptide 2 on Intestinal Microbiota in SD Rats.
AB  - Recent research suggests that intestinal microbiota affect the aging process.
      Glucagon-like peptide 2 (GLP-2), a growth factor found in the intestinal mucosal
      epithelium, reduces intestinal permeability and affects intestinal microbiota.
      The relationship between aging, GLP-2, and intestinal microbiota are still not
      well understood. The current study examined the influence of aging and GLP-2 on
      the intestinal microbiota of rats. Twelve 3-month old male SD rats were randomly
      divided into two groups: a young control group (group C) and a young GLP-2
      treatment group (group G). Twelve 26-month old male SD rats were randomly divided
      into two groups: an aged control group (group L) and an aged GLP-2 treatment
      group (group T). GLP-2 was intraperitoneally injected into rats from group G and
      group T for 14 days. Plasma GLP-2 concentration was evaluated by ELISA tests.
      Fresh intestinal stool samples were collected from each group and total fecal
      bacterial genomic DNA was extracted from the associated rats. The bacterial
      composition of fecal samples was analyzed by Miseq high-throughput sequencing and
      comparison with SRA databases. Overall, the diversity of intestinal microbiota
      significantly decreases with age in SD rats, while GLP-2 has no significant
      effect on the diversity of intestinal microbiota. Upon aging, there is a
      reduction in probiotic bacteria and a concomitant increase in pathogenic bacteria
      in rats. Treatment with GLP-2 results in a significant reduction in the
      prevalence of pathogenic bacterial genera and an increase in some potential
      benefit bacteria in aged rats. In addition, treatment with GLP-2 results in an
      increase in several probiotics and a reduction in the prevalence of pathogenic
      bacterial genera in young rats.

PMID- 30090648
TI  - Synergistically Induced Hypothermia and Enhanced Neuroprotection by
      Pharmacological and Physical Approaches in Stroke.
AB  - Hypothermia is considered as a promising neuroprotective treatment for ischemic
      stroke but with many limitations. To expand its clinical relevance, this study
      evaluated the combination of physical (ice pad) and pharmacological [transient
      receptor potential vanilloid channel 1 (TRPV1) receptor agonist, dihydrocapsaicin
      (DHC)] approaches for faster cooling and stronger neuroprotection. A total of 144
      male Sprague Dawley rats were randomized to 7 groups: sham (n=16), stroke only
      (n=24), stroke with physical hypothermia at 31oC for 3 h after the onset of
      reperfusion (n=24), high-dose DHC (H-DHC)(1.5 mg/kg, n=24), low-dose DHC (L
      DHC)(0.5 mg/kg, n=32) with (n=8) or without (n=24) external body temperature
      control at ~38 oC (L-DHC, 38 oC), and combination therapy (L-DHC+ ice pad, n=24).
      Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Infarct
      volume, neurological deficits and apoptotic cell death were determined at 24 h
      after reperfusion. Expression of pro- and anti-apoptotic proteins was evaluated
      by Western blot. ATP and reactive oxygen species (ROS) were detected by
      biochemical assays at 6 and 24 h after reperfusion. Combination therapy of L-DHC
      and ice pad significantly improved every measured outcome compared to
      monotherapies. Combination therapy achieved hypothermia faster by 28.6% than ice
      pad, 350% than L-DHC and 200% than H-DHC alone. Combination therapy reduced
      (p<0.05) neurological deficits by 63% vs. 26% with L-DHC. No effect was observed
      when using ice pad or H-DHC alone. L-DHC and ice pad combination improved brain
      oxidative metabolism by reducing (p<0.05) ROS at 6 and 24 h after reperfusion and
      increasing ATP levels by 42.9% compared to 25% elevation with L-DHC alone.
      Finally, combination therapy decreased apoptotic cell death by 48.5% vs. 24.9%
      with L-DHC, associated with increased anti-apoptotic protein and reduced pro
      apoptotic protein levels (p<0.001). Our study has demonstrated that combining
      physical and pharmacological hypothermia is a promising therapeutic approach in
      ischemic stroke, and warrants further translational investigations.

PMID- 30090649
TI  - Fucoidan Protects Dopaminergic Neurons by Enhancing the Mitochondrial Function in
      a Rotenone-induced Rat Model of Parkinson's Disease.
AB  - The mitochondrion is susceptible to neurodegenerative disorders such as
      Parkinson's disease (PD). Mitochondrial dysfunction has been considered to play
      an important role in the dopaminergic degeneration in PD. However, there are no
      effective drugs to protect mitochondria from dysfunction during the disease
      development. In the present study, fucoidan, a sulfated polysaccharide derived
      from Laminaria japonica, was investigated and characterized for its protective
      effect on the dopamine system and mitochondrial function of dopaminergic neurons
      in a rotenone-induced rat model of PD. We found that chronic treatment with
      fucoidan significantly reversed the loss of nigral dopaminergic neurons and
      striatal dopaminergic fibers and the reduction of striatal dopamine levels in PD
      rats. Fucoidan also alleviated rotenone-induced behavioral deficits. Moreover,
      the mitochondrial respiratory function as detected by the mitochondrial oxygen
      consumption and the expression of peroxisome proliferator-activated receptor
      gamma coactivator 1-alpha (PGC-1alpha) and nuclear transcription factor 2 (NRF2)
      were reduced in the substantia nigra of PD rats, which were markedly reversed by
      fucoidan. Oxidative products induced by rotenone were significantly reduced by
      fucoidan. Taken together, these results demonstrate that fucoidan possesses the
      ability to protect the dopamine system in PD rats. The neuroprotective effect of
      fucoidan may be mediated via reserving mitochondrial function involving the PGC
      1alpha/NRF2 pathway. This study provides new evidence that fucoidan can be
      explored in PD therapy.

PMID- 30090650
TI  - Neuroprotective Effect of Caffeic Acid Phenethyl Ester in A Mouse Model of
      Alzheimer's Disease Involves Nrf2/HO-1 Pathway.
AB  - Alzheimer's disease (AD) is a progressive pathology, where dementia symptoms
      gradually worsen over a number of years. The hallmarks of AD, such as amyloid
      beta-peptide (Abeta) in senile plaque and neurofibrillary tangles, are strongly
      intertwined with oxidative stress, which is considered one of the common
      effectors of the cascade of degenerative events. The endogenous nuclear factor
      erythroid 2-related factor 2 (Nrf2) is the "master regulator" of the antioxidant
      response and it is known as an indicator and regulator of oxidative stress. The
      present study aimed to determine the potential neuroprotective activity of
      caffeic acid phenethyl ester (CAPE), a polyphenolic compound abundant in
      honeybee, against the neurotoxicity of Abeta1-42 oligomers (AbetaO) in mice. An
      intracerebroventricular (i.c.v.) injection of AbetaO into the mouse brain
      triggered increased reactive oxygen species levels, neurodegeneration,
      neuroinflammation, and memory impairment. In contrast, the intraperitoneal
      administration of CAPE (10 mg/kg) after i.c.v. AbetaO-injection counteracted
      oxidative stress accompanied by an induction of Nrf2 and heme oxygenase-1 via the
      modulation of glycogen synthase kinase 3beta in the hippocampus of mice.
      Additionally, CAPE treatment decreased AbetaO-induced neuronal apoptosis and
      neuroinflammation, and improved learning and memory, protecting mice against the
      decline in spatial cognition. Our findings demonstrate that CAPE could
      potentially be considered as a promising neuroprotective agent against
      progressive neurodegenerative diseases such as AD.

PMID- 30090651
TI  - Involvement of Kif4a in Spindle Formation and Chromosome Segregation in Mouse
      Oocytes.
AB  - Kif4a, a member of the kinesin superfamily, has been reported to participate in a
      series of cellular processes such as chromosome condensation and cytokinesis
      during mitosis. However, the roles of KIF4a in meiosis are still unknown. In
      present study we found that the Kif4a protein expression decreased in maternal
      aged mouse oocytes. We then explored the roles of Kif4a in mouse oocyte meiosis
      by knockdown analysis. Kif4a was enriched at the spindle during mouse oocyte
      maturation. By specific knock down of the Kif4a using morpholino microinjection,
      we found that the disruption of Kif4a caused the failure of polar body extrusion.
      Further analysis indicated that Kif4a might affect the spindle morphology and
      chromosome alignment in the mouse oocytes, and this might be due to the
      regulation of tubulin acetylation. Moreover, our results showed that an increased
      proportion of aneuploidy in the Kif4a knock down oocytes, and this might be due
      to the loss of kinetochore-microtubule attachment. Taken together, these results
      suggested that Kif4a possibly regulated mouse oocyte meiosis through its effects
      on the spindle organization and accurate chromosome segregation, and the loss of
      Kif4a might be related with aneuploidy of aging oocytes.

PMID- 30090652
TI  - Gait Analyses in Mice: Effects of Age and Glutathione Deficiency.
AB  - Minor changes (~0.1 m/s) in human gait speed are predictive of various measures
      of decline and can be used to identify at-risk individuals prior to further
      decline. These associations are possible due to an abundance of human clinical
      research. However, age-related gait changes are not well defined in rodents, even
      though rodents are used as the primary pre-clinical model for many disease states
      as well as aging research. Our study investigated the usefulness of a novel
      automated system, the CatWalkTM XT, to measure age-related differences in gait.
      Furthermore, age-related functional declines have been associated with decreases
      in the reduced to oxidized glutathione ratio leading to a pro-oxidizing cellular
      shift. Therefore the secondary aim of this study was to determine whether chronic
      glutathione deficiency led to exacerbated age-associated impairments. Groups of
      male and female wild-type (gclm+/+) and knock-out (gclm-/-) mice aged 4, 10 and
      17 months were tested on the CatWalk and gait measurements recorded. Similar age
      related declines in all measures of gait were observed in both males and females,
      and chronic glutathione depletion was associated with some delays in age-related
      declines, which were further exacerbated. In conclusion, the CatWalk is a useful
      tool to assess gait changes with age, and further studies will be required to
      identify the potential compensating mechanisms underlying the effects observed
      with the chronic glutathione depletion.

PMID- 30090653
TI  - Pkcdelta Activation is Involved in ROS-Mediated Mitochondrial Dysfunction and
      Apoptosis in Cardiomyocytes Exposed to Advanced Glycation End Products (Ages).
AB  - Diabetic patients exhibit serum AGE accumulation, which is associated with
      reactive oxygen species (ROS) production and diabetic cardiomyopathy. ROS-induced
      PKCdelta activation is linked to mitochondrial dysfunction in human cells.
      However, the role of PKCdelta in cardiac and mitochondrial dysfunction caused by
      AGE in diabetes is still unclear. AGE-BSA-treated cardiac cells showed dose- and
      time-dependent cell apoptosis, ROS generation, and selective PKCdelta activation,
      which were reversed by NAC and rotenone. Similar tendency was also observed in
      diabetic and obese animal hearts. Furthermore, enhanced apoptosis and reduced
      survival signaling by AGE-BSA or PKCdelta-WT transfection were reversed by kinase
      deficient (KD) of PKCdelta transfection or PKCdelta inhibitor, respectively,
      indicating that AGE-BSA-induced cardiomyocyte death is PKCdelta-dependent.
      Increased levels of mitochondrial mass as well as mitochondrial fission by AGE
      BSA or PKCdelta activator were reduced by rottlerin, siPKCdelta or KD
      transfection, indicating that the AGE-BSA-induced mitochondrial damage is
      PKCdelta-dependent. Using super-resolution microscopy, we confirmed that PKCdelta
      colocalized with mitochondria. Interestingly, the mitochondrial functional
      analysis by Seahorse XF-24 flux analyzer showed similar results. Our findings
      indicated that cardiac PKCdelta activation mediates AGE-BSA-induced cardiomyocyte
      apoptosis via ROS production and may play a key role in the development of
      cardiac mitochondrial dysfunction in rats with diabetes and obesity.

PMID- 30090654
TI  - N-acetylcysteine Treatment Reduces Age-related Hearing Loss and Memory Impairment
      in the Senescence-Accelerated Prone 8 (SAMP8) Mouse Model.
AB  - Age-related hearing loss (ARHL) is the most common sensory disorder in the
      elderly population. SAMP8 mouse model presents accelerated senescence and has
      been identified as a model of gerontological research. SAMP8 displays a
      progressive age-related decline in brain function associated with a progressive
      hearing loss mimicking human aging memory deficits and ARHL. The molecular
      mechanisms associated with SAMP8 senescence process involve oxidative stress
      leading to chronic inflammation and apoptosis. Here, we studied the effect of N
      acetylcysteine (NAC), an antioxidant, on SAMP8 hearing loss and memory to
      determine the potential interest of this model in the study of new antioxidant
      therapies. We observed a strong decrease of auditory brainstem response
      thresholds from 45 to 75 days of age and an increase of distortion product
      amplitudes from 60 to 75 days in NAC treated group compared to vehicle. Moreover,
      NAC treated group presented also an increase of memory performance at 60 and 105
      days of age. These results confirm that NAC delays the senescence process by
      slowing the age-related hearing loss, protecting the cochlear hair cells and
      improving memory, suggesting that antioxidants could be a pharmacological target
      for age-related hearing and memory loss.

PMID- 30090655
TI  - Hyperglycemia Alters Astrocyte Metabolism and Inhibits Astrocyte Proliferation.
AB  - Diabetes milieu is a complex metabolic disease that has been known to associate
      with high risk of various neurological disorders. Hyperglycemia in diabetes could
      dramatically increase neuronal glucose levels which leads to neuronal damage, a
      phenomenon referred to as glucose neurotoxicity. On the other hand, the impact of
      hyperglycemia on astrocytes has been less explored. Astrocytes play important
      roles in brain energy metabolism through neuron-astrocyte coupling. As the
      component of blood brain barrier, glucose might be primarily transported into
      astrocytes, hence, impose direct impact on astrocyte metabolism and function. In
      the present study, we determined the effect of high glucose on the energy
      metabolism and function of primary astrocytes. Hyperglycemia level glucose (25
      mM) induced cell cycle arrest and inhibited proliferation and migration of
      primary astrocytes. Consistently, high glucose decreased cyclin D1 and D3
      expression. High glucose enhanced glycolytic metabolism, increased ATP and
      glycogen content in primary astrocytes. In addition, high glucose activated AMP
      activated protein kinase (AMPK) signaling pathway in astrocytes. In summary, our
      in vitro study indicated that hyperglycemia might impact astrocyte energy
      metabolism and function phenotype. Our study provides a potential mechanism which
      may underlie the diabetic cerebral neuropathy and warrant further in vivo study
      to determine the effect of hyperglycemia on astrocyte metabolism and function.

PMID- 30090656
TI  - Glibenclamide Enhances the Therapeutic Benefits of Early Hypothermia after Severe
      Stroke in Rats.
AB  - Glibenclamide (GBC) is an antidiabetic drug that is in a class of medications
      known as sulfonylureas, which play critical roles in attenuating brain edema and
      reducing mortality in ischemic stroke patients. Therapeutic hypothermia (TH) is
      another robust neuroprotectant that prevents brain swelling and improves the
      neurological outcomes of stroke patients. However, whether the combination of GBC
      and TH can be used as a reliable neuroprotectant in ischemic stroke remains
      largely unknown. We used the middle cerebral artery occlusion (MCAO) rat model as
      well as oxygen and glucose deprivation-reoxygenation (OGD/R) endothelial cells as
      ischemic stroke models to investigate the efficacy and mechanisms of treating
      ischemic stroke with the combination of GBC and TH. The serum glucose, mortality
      rate, neurobehavioral functions, tight junctions, endothelial cells and
      inflammatory cytokines were evaluated in the stroke models after treatment with
      GBC, TH or the combination of them. After 5-hour occlusion and subsequent
      reperfusion, rats exhibited a large volume of hemispheric swelling and a high
      mortality rate. Stroke rats treated with the combined therapy did not exhibit
      hypoglycemia. The combination of GBC and TH exhibited synergistic neuroprotective
      effects in stroke rats that were associated with greater reductions in edema
      volume, better improvement in neurobehavioral functions, prevention of tight
      junction loss, and reduction of expression of the inflammatory cytokines COX-2
      and iNOS. In OGD/R endothelia cells, the combination reduced endothelial cell
      death. This study demonstrated that both GBC and TH are neuroprotective after the
      severe stroke; however, combined therapy with GBC and TH enhanced the efficiency
      and efficacy of the effects of TH and GBC in the treatment of ischemia. This
      combined therapy may facilitate the clinical translation of TH management for
      severe stroke. The combination of GBC and TH seems to be a feasible and promising
      clinical strategy to alleviate cerebral injury following severe stroke.

PMID- 30090657
TI  - The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in
      Patients with Early-Onset Dementia.
AB  - Our study aimed to identify the underlying causes in patients with early onset
      dementia by clinical and genetic exploration. We recruited a group of 38 patients
      with early-onset dementia. Firstly, hexanucleotide repeat expansions in C9ORF72
      gene were screened in all subjects to exclude the possibility of copy number
      variation. Then, the whole exome sequencing (WES) was conducted, and the data
      were analyzed focusing on 89 dementia-related causing and susceptible genes. The
      effects of identified variants were classified according to the American College
      of Medical Genetics and Genomics (ACMG) standards and guidelines. There were no
      pathogenic expansions in C9ORF72 detected. According to the ACMG standards and
      guidelines, we identified five known pathogenic mutations, PSEN1 P284L,
      PSEN1c.857-1G>A, PSEN1 I143T, PSEN1 G209E and MAPT G389R, and one novel
      pathogenic mutation APP K687N. All these mutations caused dementia with the mean
      onset age of 38.3 (range from 27 to 51) and rapid progression. Eleven variants
      with uncertain significance were also detected and needed further verification.
      The clinical phenotypes of dementia are heterogeneous, with both onset ages and
      clinical features being influenced by mutation position as well as the causative
      gene. WES can serve as efficient diagnostic tools for different heterogeneous
      dementia.

PMID- 30090658
TI  - The Prevalence of Mild Cognitive Impairment in China: A Systematic Review.
AB  - The aim of this study was to analyze the prevalence of mild cognitive impairment
      (MCI) among the aging population (60 years of age and above) in China.
      Epidemiological investigations on MCI in online Chinese journals were identified
      manually using the CQVIP, CNKI, and Wanfang databases. Articles from journals
      published in English were identified using PubMed and Web of Science. Original
      studies that included prevalence surveys of MCI were selected. Forty-eight
      relevant studies were included in the analysis, covering 22 provinces in China.
      Our results showed that the pooled prevalence of MCI in the older Chinese
      population was 14.71% (95% confidence interval [CI], 14.50-14.92%). The
      prevalence was 16.72% (95% CI, 15.68-17.71%) in clinical samples vs. 14.61% (95%
      CI, 14.40-14.83%) in nonclinical samples (chi2=16.60, P<0.01), and 15.20% (95%
      CI, 14.91-15.49%) in screened samples vs. 14.16% (95% CI, 13.85-14.46%) in
      diagnosed samples (chi2=22.11, P<0.01). People of older age, of female sex, or
      living in rural areas or western China were associated with a higher prevalence
      of MCI. The prevalence of MCI was high in Chinese older adults, and even higher
      in those who were older, female, or living in rural areas or western China.
      Future studies are recommended to address the prevalence of MCI in the other 12
      provinces of China. Furthermore, diagnostic assessments should be included in the
      identification of MCI.

PMID- 30090659
TI  - Superoxide Radical Dismutation as New Therapeutic Strategy in Parkinson's
      Disease.
AB  - Aging is the biggest risk factor for developing many neurodegenerative disorders,
      including idiopathic Parkinson's disease (PD). PD is still an incurable disorder
      and the available medications are mainly directed to the treatment of symptoms in
      order to improve the quality of life. Oxidative injury has been identified as one
      of the principal factors involved in the progression of PD and several
      indications are now reported in the literature highlighting the prominent role of
      the superoxide radical in inducing neuronal toxicity. It follows that superoxide
      anions represent potential cellular targets for new drugs offering a novel
      therapeutic approach to cope with the progression of the disease. In this review
      we first present a comprehensive overview of the most common cellular reactive
      oxygen and nitrogen species, describing their cellular sources, their potential
      physiological roles in cell signalling pathways and the mechanisms through which
      they could contribute to the oxidative damage. We then analyse the potential
      therapeutic use of SOD-mimetic molecules, which can selectively remove superoxide
      radicals in a catalytic way, focusing on the classes of molecules that have
      therapeutically exploitable properties.

PMID- 30090661
TI  - Kidney Disease in Elderly: Importance of Collaboration between Geriatrics and
      Nephrology.
AB  - The population in the United States is aging and presents many challenges in the
      healthcare world. According to the report released by United States Census Bureau
      in June 2017, there are around 50 million residents aged 65 years and over as of
      2016. Among the multiple healthcare challenges, kidney disease is a significant
      one because of its high burden, high cost and low awareness. Medicare spending on
      chronic kidney disease for 65 plus aged patients exceeded $ 50 billion in 2013.
      Different studies based on different calculations have estimated that at least
      one-third of chronic kidney disease patients are aged above 65 years. Most of the
      chronic kidney disease patients have multiple medical co-morbidities but
      geriatric syndromes are added factors that may be challenging for nephrologists.
      There is scarcity of well-trained geriatricians and in most instances,
      nephrologists take over the role of internist or geriatrician. This article
      outlines the need and importance of collaboration and coordination between
      geriatrics and nephrology for the best patient care and better healthcare
      outcomes.

PMID- 30090660
TI  - Mitochondrial Pharmacology of Dimebon (Latrepirdine) Calls for a New Look at its
      Possible Therapeutic Potential in Alzheimer's Disease.
AB  - Dimebon (latrepirdine), an old antihistaminic drug, showed divergent results in
      two large clinical trials in Alzheimer disease (AD), which according to our
      review might be related to the specific pharmacological properties of the drug
      and the different patient populations included in both studies. Out of the many
      pharmacological effects of Dimebon, improvement of impaired mitochondrial
      function seeems to be most relevant for the substantial effects on cognition and
      behaviour reported in one of the studies, as these effects are already present at
      the low concentrations of dimebon measured in plasma and tissues of patients and
      experimental animals. Since impaired mitochondrial function seems to be the major
      driving force for the progression of the clinical symptoms and since most of the
      clinical benefits of dimebon originate from an effect on the symptomatic
      deterioration, mitochondrial improvement can also explain the lack of efficacy of
      this drug in another clinical trial where symptoms of the patiets remained stable
      for the time of the study. Accordingly, it seems worthwhile to reevaluate the
      clinical data to proof that clinical response is correlated with high levels of
      Neuropsychiatric Symptoms as these show a good relationship to the individual
      speed of symptomatic decline in AD patients related to mitochondrial dysfunction.

PMID- 30090662
TI  - Removal of Chylomicron Remnants from the Bloodstream is Delayed in Aged Subjects.
AB  - Dietary fats absorbed in the intestine are transported in the circulation as
      chylomicrons and remnants that have atherogenic potential. Although postprandial
      lipidemia is increased in older subjects, the specific chylomicron metabolism has
      not been explored in older subjects nor compared to young subjects, which is the
      focus of this study. After a 12 h fast, artificially-made emulsions similar to
      lymph chylomicrons and doubly labeled with radioactive cholesteryl esters and
      triglycerides were intravenously injected in 23 older (66+/-4 years) and 20 young
      (24+/-3 years) subjects. Sequential blood samples were collected to determine
      fractional clearance rates (FCR, in min-1) by compartmental analysis. Older
      subjects had higher LDL-cholesterol (p<0.001) and triglycerides (p<0.0001) than
      young subjects; HDL-cholesterol presented no difference. The emulsion cholesteryl
      ester FCR was lower in older subjects compared to the young (p=0.0001). The
      emulsion triglyceride FCR did not differ in the two groups. Tested in vitro,
      however, the lipolysis of the emulsion triglycerides was less intense in the
      older than in the young subjects. As delayed removal of remnants, indicated by
      the pronouncedly smaller cholesteryl ester FCR, is related to the presence of
      cardiovascular diseases, this can be a risk factor which could accelerate
      atherogenic complications occurring in aged subjects.

PMID- 30090663
TI  - Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) on
      3-tesla Normal Database: Diagnostic Accuracy in Two Independent Cohorts with
      Early Alzheimer's Disease.
AB  - Voxel-based specific regional analysis system for Alzheimer's disease (VSRAD)
      software is widely used in clinical practice in Alzheimer's disease (AD). The
      existing VSRAD is based on the normal database with 1.5-tesla MRI scans (VSRAD
      1.5T), and its utility for patients have undergone 3-tesla MRI is still
      controversial. We recruited 19 patients with early AD and 28 healthy controls who
      had undergone 3-tesla MRI scans at our institute (Cohort 1). We also used the 3
      tesla MRI data of 30 patients with early AD and 13 healthy controls from the
      Japanese Alzheimer's Disease Neuroimaging Initiative (Cohort 2). We also created
      a new VSRAD based on 65 normal subjects' 3-tesla MRI scans (VSRAD-3T), and
      compared the detectability of AD between VSRAD-1.5T and VSRAD-3T, using receiver
      operating characteristic curve and area under the curve (AUC) analyses. As a
      result, there were no significant differences in the detectability of AD between
      VSRAD-3T and VSRAD-1.5T, except for the whole white matter atrophy score, which
      showed significantly better AUC in VSRAD-3T than in VSRAD-1.5T in both Cohort 1
      (p=0.04) and 2 (p<0.01). Generally, there were better diagnostic values in Cohort
      2 than in Cohort 1. The optimal cutoff values varied but were generally lower
      than in the previously published data. In conclusion, for patients with 3-tesla
      MRI, the detectability of early AD by the existing VSRAD was not different from
      that by the new VSRAD based on 3-tesla database. We should exercise caution when
      using the existing VSRAD for 3-tesla white matter analyses or for setting cutoff
      values.

PMID- 30090664
TI  - Hypoxia, hibernation and Neuroprotection: An Experimental Study in Mice.
AB  - Hibernation is a unique physiological state that evolved to survive periods of
      food shortages. It is characterized by profound decreases in metabolic rate, body
      temperature and physiological functions. Studies have shown that animals in
      hibernation can resist neurological damage. Here, we aimed to study whether
      hypoxia can induce a hibernation-like state in a traditionally non-hibernating
      animal and whether it is neuroprotective. All procedures were conducted according
      to international guidelines on laboratory animal safety. Mice C57BL/6 (19-21g)
      were placed into a 125 mL jar with fresh air and the jar was sealed with a rubber
      plug. For each run, the tolerance limit was judged by the animals' appearance for
      "air hunger". The animal was removed from the jar as soon as its first gasping
      breath appeared and was moved to another fresh-air-containing jar of similar
      volume. This procedure was performed in four runs. The hypoxia exposure
      significantly decreased oxygen (O2) consumption, carbon dioxide (CO2) production,
      respiratory rate and heart rate. Meanwhile, rectal temperature reached a minimum
      of 12.7+/-2.56 degrees C, which is lower than a wide range of ambient
      temperatures. The mimicked hibernation decreased the infarct size in a focal
      cerebral ischemia mouse model. Our findings suggest the possibility of inducing
      suspended animation-like hibernation states for medical applications post injury.

PMID- 30090665
TI  - Role of bevacizumab for treatment-refractory meningiomas: A systematic analysis
      and literature review.
AB  - Background: Meningiomas are the most prevalent primary tumor of the central
      nervous system (CNS), and although the majority of these neoplasms are classified
      as benign, nearly one fourth of the lesions display an aggressive profile
      characterized by pleomorphic histology, high recurrence rates, and overall
      resistance to standard treatment. Despite the ubiquitous nature of these tumors,
      no adjuvant therapeutic regimen has been identified which effectively controls
      disease recurrence and progression after surgery and radiation, leading to a
      dismal prognosis in this patient population. The primary focus of this research
      study is, hence, to assess the recently emerging use of bevacizumab, an anti
      angiogenic agent, in the treatment of meningiomas. This systematic literature
      review analyzes the efficacy and safety of therapeutic bevacizumab for treatment
      refractory meningiomas. Methods: A systematic PubMed search was conducted
      according to PRISMA guidelines to identify all relevant reports investigating the
      anti-angiogenic agent bevacizumab in the treatment of intracranial meningiomas.
      The reported parameters from pertinent retrospective reviews, prospective
      studies, and case studies were volumetric reduction, radiographic response,
      clinical stability, overall survival (OS), and progression free survival (PFS)
      measured at 6 and 12 months postinitiation of treatment. Complications were
      cataloged based on the range and severity of the therapy-related toxicities.
      Results: A total of 11 articles, 5 retrospective series, 2 prospective trials,
      and 4 case reports, reporting on a total of 92 patients, were included in this
      review. The use of bevacizumab therapy for intracranial meningiomas demonstrated
      median overall PFS of 16.8 months (range: 6.5-22 months) and PFS-6 of 73% (range:
      44%-93%). Conclusions: Therapeutic bevacizumab, either alone or with combination
      chemotherapies, for select patient populations with recurrent or progressive
      meningiomas, offers a treatment option that confers improved overall progression
      free survival. To assess OS parameters, larger randomized controlled trials
      assessing the use of anti-angiogenic agents for recurrent/progressive meningiomas
      are warranted.

PMID- 30090666
TI  - Surgical and neurological complications in temporal lobe epilepsy surgery in
      modern era.
AB  - Background: Temporal lobe epilepsy is the most common form of focal epilepsy, and
      surgical treatment has been proven to be an effective and safe management.
      Despite its safety, it is important to know that some complications and/or even
      death can be seen after surgery. Neurosurgeons should be able to precisely inform
      epilepsy surgery candidates about the possible unwanted/unexpected conditions
      after surgery. Methods: Fifty-three patients who underwent anterior temporal lobe
      resection due to temporal lobe epilepsy by a single surgeon were investigated
      retrospectively regarding postoperative surgical and neurological complications.
      Results: Overall complication rate was found to be 19%, surgical complications
      comprised 13.2% whereas neurological complications were 5.8%. Three patients
      underwent a second surgery whereas the rest had medical treatment or recovered
      spontaneously. Fortunately persistent complication rate was found to be 0%, and
      there was no mortality. Conclusions: Anterior temporal lobe resection is a safe
      and very effective surgical modality for the treatment of temporal lobe epilepsy.
      However, unexpected complications may be possible in this modern era and a
      surgeon should trust in him/herself not in modern equipments.

PMID- 30090667
TI  - Endovascular reconstruction for a kinked internal carotid artery after carotid
      endarterectomy.
AB  - Background: Although different surgical techniques have been reported for
      repairing kinked stenosis of the internal carotid artery (ICA) after carotid
      endarterectomy (CEA), there are no reports using endovascular reconstruction. We
      present the details of a case successfully treated by carotid artery stenting
      (CAS). Case Description: A 73-year-old female was referred to our department with
      fugacious amaurosis and transient sensory disturbance in the left upper limb due
      to moderate stenosis of the right ICA that was treated by CEA 28 days after
      admission. However, postoperative angiography and carotid Doppler revealed a
      kinked ICA with a high-flow velocity that was not present intraoperatively. After
      3 months, she had suffered transient ischemic attacks that were refractory to
      medical treatment, so we performed CAS to prevent future events. The kinked ICA
      was immediately resolved by stenting and there was no restenosis at a follow-up
      angiogram 19 months later. Conclusions: This case shows that CAS could be a
      potential therapeutic option for the management of symptomatic kinking stenosis
      of the ICA after CEA.

PMID- 30090668
TI  - White cord syndrome: A devastating complication of spinal decompression surgery.
AB  - Background: Reperfusion injury of the spinal cord or "white cord syndrome" refers
      to the sudden onset of neurological deterioration after spinal decompressive
      surgery. Associated magnetic resonance (MR) findings only include focal
      hyperintensity on T2-weighted images without any other pathological changes. Case
      Description: A patient with cervical stenosis secondary to metastatic tumor in
      the intradural and extradural compartments presented with lower limb paraparesis.
      She underwent an uneventful tumor excision accompanied by posterior cervical
      decompression and fusion. Postoperatively, she was quadriplegic and required
      ventilator support. The emergent postoperative MR scan revealed focal
      hyperintensity on the T2-weighted image consistent with spinal cord edema
      extending into the lower brain stem. Conclusion: Very few cases of reperfusion
      injury of the cervical spinal cord or "white cord syndrome" are described in the
      literature. Here we present a patient who, following cervical laminectomy and
      fusion for excision of metastatic tumor, developed quadriplegia. Notably,
      postoperative MR showed only findings of upper cervical cord and lower brain stem
      edema consistent with a "white cord syndrome" without other compressive
      pathology.

PMID- 30090669
TI  - Risk Factors for Depression Among Civilians After the 9/11 World Trade Center
      Terrorist Attacks: A Systematic Review and Meta-Analysis.
AB  - Introduction: The development of depressive symptoms among the population of
      civilians who were not directly involved in recovery or rescue efforts following
      the 9/11 World Trade Center (WTC) terrorist attacks is not comprehensively
      understood. We performed a meta-analysis that examined the associations between
      multiple risk factors and depressive symptoms after the 9/11 WTC terrorist
      attacks in New York City among civilians including survivors, residents, and
      passersby. Methods: PubMed, Google Scholar, and the Cochrane Library were
      searched from September, 2001 through July, 2016. Reviewers identified eligible
      studies and synthesized odds ratios (ORs) using a random-effects model. Results:
      The meta-analysis included findings from 7 studies (29,930 total subjects). After
      adjusting for multiple comparisons, depressive symptoms were significantly
      associated with minority race/ethnicity (OR, 1.40; 99.5% Confidence Interval
      [CI], 1.04 to 1.88), lower income level (OR, 1.25; 99.5% CI, 1.09 to 1.43), post
      9/11 social isolation (OR, 1.68; 99.5% CI, 1.13 to 2.49), post-9/11 change in
      employment (OR, 2.06; 99.5% CI, 1.30 to 3.26), not being married post-9/11 (OR,
      1.59; 99.5% CI, 1.18 to 2.15), and knowing someone injured or killed (OR, 2.02;
      99.5% CI, 1.42 to 2.89). Depressive symptoms were not significantly associated
      with greater age (OR, 0.86; 99.5% CI, 0.70 to 1.05), no college degree (OR, 1.32;
      99.5% CI, 0.96 to 1.83), female sex (OR, 1.24; 99.5% CI, 0.98 to 1.59), or direct
      exposure to WTC related traumatic events (OR, 1.26; 99.5% CI, 0.69 to 2.30).
      Discussion: Findings from this study suggest that lack of post-disaster social
      capital was most strongly associated with depressive symptoms among the civilian
      population after the 9/11 WTC terrorist attacks, followed by bereavement and
      lower socioeconomic status. These risk factors should be identified among
      civilians in future disaster response efforts.

PMID- 30090670
TI  - Delayed Birth-Related Femur Fracture after Cesarean Section: A Case Report.
AB  - Background  Birth-related femur fractures are rare. They have been reported
      following difficult delivery and are commonly diagnosed immediately after birth
      or on the following day. However, some birth-related femur fractures are
      diagnosed several days after birth. Mechanisms underlying the development of
      delayed femur fracture are incompletely understood. Case  We report the case of a
      girl diagnosed with a left spiral femur fracture with associated edema and
      hypoesthesia on postpartum day 9. A nondisplacement femur fracture was identified
      on plain radiography at birth after cesarean section; however, it was undiagnosed
      due to the lack of symptoms. She was treated with plaster cast fixation; the
      physical examination at age 1 was normal. Herein, the diagnosis of birth-related
      femur fracture according to plain radiography findings suggests that the symptoms
      related to birth trauma develop several days after birth. Conclusion  Birth
      related fracture should be considered in all neonatal femur fracture cases and in
      patients with no symptoms at birth. Neonates delivered in the breech presentation
      by cesarean section should be carefully monitored after birth. The findings of
      the present case further our understanding of the pathogenic mechanisms
      underlying delayed diagnosis of birth-related femur fracture.

PMID- 30090671
TI  - ELECTROMYOGRAPHY OF THE HIP AND THIGH MUSCLES DURING TWO VARIATIONS OF THE LUNGE
      EXERCISE: A CROSS-SECTIONAL STUDY.
AB  - Background: The lunge is a closed kinetic chain exercise that athletes frequently
      use as part of training and rehabilitative programs. While typically performed on
      a stable surface, modifications include the use of balance platforms to create an
      unstable surface and suspension equipment. Suspension training exercises are
      theorized to be higher demand exercises and may be considered a progression from
      exercises on stable surfaces. Comparison of muscle recruitment between the
      suspended lunge and the standard lunge has not been reported. Hypothesis and
      purpose: The purpose was to compare differences in muscle recruitment between a
      standard lunge and a suspended lunge. We hypothesized that hip and thigh muscle
      recruitment with a suspended lunge would be greater than a standard lunge due to
      less inherent support with the suspended lunge exercise. Study Design: Analytic,
      observational cross-sectional study design. Methods: Thirty healthy participants
      (15 male and 15 female) voluntarily participated in this study. Electromyographic
      (EMG) muscle recruitment was measured in five hip and thigh muscles while
      performing a standard and suspended lunge. EMG was expressed as a percentage of
      EMG with a maximal voluntary isometric contraction (MVIC). Results: Recruitment
      was significantly greater in the suspended lunge condition compared to the
      standard lunge for the hamstrings (p < .001), gluteus medius (p < .001), gluteus
      maximus (p<.001), and adductor longus (p < .001). There was no significant
      difference in rectus femoris recruitment between conditions (p = .154).
      Conclusion: Based on EMG findings, the suspended lunge is a more demanding
      exercise for hip muscles, compared to the standard lunge. Level of evidence:
      Level 3 Mechanism-based reasoning intervention study trial. Clinical relevance:
      The results of this study can assist clinicians in designing and progressing
      lower extremity exercise programs. With greater muscle recruitment, the suspended
      lunge is a more demanding exercise for hip muscles and can be considered a
      progression of the standard lunge as part of an exercise program. What is known
      about the subject?: Muscle recruitment associated with the lunge exercise,
      variations of the lunge, and similar exercises has been reported. The use of
      suspension training exercise equipment has been reported for upper extremity
      exercises however not for the lower extremity. What does this study add to
      existing knowledge?: Results of this study provide novel EMG information related
      to the lunge exercise using suspension training exercise equipment. Clinicians
      can use this information designing lower extremity exercise programs.

PMID- 30090672
TI  - COMPARISON OF CLINICAL FATIGUE PROTOCOLS TO DECREASE SINGLE-LEG FORWARD HOP
      PERFORMANCE IN HEALTHY INDIVIDUALS.
AB  - Background: Return to activity decisions after anterior cruciate ligament
      reconstruction (ACL-R) are limited by functional performance tests often
      performed in a non-fatigued state. Fatigue can improve test sensitivity, but
      current methods to induce fatigue are typically bilateral tasks or focus on the
      quadriceps muscle in isolation. Hypothesis/Purpose: To determine the effects of a
      two-minute lateral step-down fatigue test compared to a 30-second side-hop test
      on single-leg forward hop distance in healthy individuals. It was hypothesized
      that participants would demonstrate decreased hop distance with both tests, but
      the two-minute lateral step-down fatigue test would result in greater deficits in
      single-leg forward hop distance. Study Design: Randomized crossover. Methods:
      Twenty healthy participants (16 females, 4 males; age = 23.7+/-3.0 years, height
      = 153.8+/-36.2 cm; mass = 64.4+/-12.8 kg; Tegner = 6.8+/-1.2) were asked to
      perform single-leg forward hop for distance pre- and post-fatigue. Participants
      were randomly assigned to one of the two fatigue tests, 30-second side-hop or 2
      minute lateral step-down test, during the first visit. They returned within a
      week and performed the same sequence of tests but underwent whichever fatigue
      test was not assigned at the prior visit. Results: There was a significant
      decrease (p < 0.001) in single-leg forward hop distance following the 30-second
      side-hop test (pre = 134.1+/-23.7 cm, post = 126.2+/-24.4 cm) and the two-minute
      lateral step-down test (pre = 135.0+/-26.1 cm, post = 122.7+/-27.4 cm). The
      decrease in hop distance was significantly greater (p < 0.001) for the two-minute
      lateral step-down test compared to the 30-second side-hop test. Conclusion: The
      two-minute lateral step-down test resulted in a greater decrease in hop
      performance compared to the 30-second side-hop test. The results establish a
      threshold for expected changes that occur in a healthy population and that can
      then be compared with an injured athlete population. The two-minute lateral step
      down exercise may be an effective method of inducing fatigue to better mimic
      performance in a sports environment to inform return-to-sport decisions. Level of
      Evidence: Level 1b- Therapy.

PMID- 30090673
TI  - RELATIONSHIP BETWEEN THE LOWER QUARTER Y-BALANCE TEST SCORES AND ISOKINETIC
      STRENGTH TESTING IN PATIENTS STATUS POST ACL RECONSTRUCTION.
AB  - Background: ACL injuries are common among sports populations and achieving
      adequate lower extremity strength is important prior to return to play. Access to
      isokinetic testing equipment that measures lower extremity strength is limited.
      Screening tools that measure functional criteria are accessible to clinicians,
      however the tools' relationship to strength constructs have not been investigated
      in an ACL reconstructed (ACLR) population. Purpose: The primary objective was to
      determine if relationships exist between isokinetic peak knee extension torque
      (PKET), peak knee flexion torque (PKFT), hamstring to quadriceps (HQ) ratios, and
      YBT-LQ performance following ACLR. The secondary objective was to observe
      differences in isokinetic strength ability between high and low performers on the
      YBT-LQ. Study Design: Retrospective Chart Review. Methods: Medical records of
      forty-five ACL-reconstructed subjects, between five-12 months post-surgery were
      queried for functional assessment data collected during the institution's
      standard outcome testing battery. Variables of interest included: demographic and
      anthropomorphic measures, YBT-LQ performance, and involved limb isokinetic PKET,
      PKFT, and HQ ratios. Performance on each measure, as well as asymmetry between
      sides, was analyzed using a correlation matrix. Results: Statistically
      significant (p<0.01) relationships were identified between YBT-LQ anterior reach
      asymmetry and the PKET deficit (r=0.264). PKET and PKFT on the involved limb
      correlated to performance of anterior reach (r=0.591, p<0.01)(r=0.493, p<0.01),
      posteromedial reach (r=0.498, p<0.01)(r=0.577, p<0.01), and posterolateral reach
      (r=0.294, p<0.05)(r=0.445, p<0.01) respectively. Similar relationships existed on
      the uninvolved side, but to a lesser extent. High and low performers on the YBT
      LQ demonstrated lower and higher extension torque deficits, respectively.
      Conclusion: While each test measures unique constructs, there are associations
      between components of the tests. In the ACLR population, both the YBT-LQ and
      isokinetic strength testing can expose asymmetries and impact return to play
      decision making. Level of evidence: 2b.

PMID- 30090674
TI  - DO MALES WITH PATELLOFEMORAL PAIN HAVE POSTEROLATERAL HIP MUSCLE WEAKNESS?
AB  - Background: Patellofemoral pain is common in physically active adults. Females
      with patellofemoral pain have been shown to have posterolateral hip muscle
      weakness, but there is a paucity of research examining hip muscle strength in
      males with patellofemoral pain. Hypothesis/Purpose: The purpose of this study was
      to examine posterolateral hip muscle strength in males with patellofemoral pain
      compared to asymptomatic males. It was hypothesized that males with
      patellofemoral pain would have decreased strength of the hip extensor, hip
      external rotator, and hip abductor muscles compared to healthy, asymptomatic
      males. Study Design: Descriptive, cross-sectional. Methods: Thirty-six adult
      males with patellofemoral pain and 36 pain-free males participated in the study.
      The patellofemoral pain group were required to have retropatellar pain reproduced
      by activities that loaded the patellofemoral joint (squatting, descending stairs,
      etc.). Peak isometric torque of the hip extensors, hip external rotators, and hip
      abductors was measured with an instrumented dynamometer. Torque was normalized by
      body mass and height. Between-group differences were analyzed with parametric or
      non-parametric tests, as appropriate. The level of significance was adjusted for
      multiple comparisons. Results: Hip extensor torque was significantly reduced in
      the patellofemoral pain group compared to the control group (p = .0165). No
      differences were found between groups for the hip external rotators or hip
      abductors (p > .0167). Conclusion: Males with patellofemoral pain appear to have
      weakness of the hip extensors, but unlike females with patellofemoral pain, they
      do not appear to have weakness of the hip abductors or hip external rotators. The
      findings of this study suggest that muscle strength factors associated with
      patellofemoral pain in males may be different from muscle strength factors in
      females. Clinicians examining and designing plans of care for male patients with
      patellofemoral pain should consider that the hip abductors and hip external
      rotators may not be weak in men with this condition. Level of evidence: Level 3.

PMID- 30090675
TI  - COMPARISON OF LUMBOPELVIC RHYTHM AMONG ADOLESCENT SOCCER PLAYERS WITH AND WITHOUT
      LOW BACK PAIN.
AB  - Background: Hip-spine incoordination can cause low back pain (LBP) in
      adolescents. Hip-spine coordination, including the lumbopelvic rhythm (LPR) and
      the lumbar-hip ratio (LHR), can be used to assess lower limb and spine function.
      However, there are no reports of the values of LPR or LHR in adolescent soccer
      players with and without LBP. Purpose: The purpose of this study was to clarify
      the effect of LBP on LPR and LHR during trunk extension among adolescent soccer
      players. Study Design: A cross-sectional observational study. Methods: One
      hundred and nine adolescent soccer players were recruited and divided into two
      groups, one with and one without LBP. Using three-dimensional motion analysis,
      participants range of motion (ROM) of the lumbar spine (LS) and hip during trunk
      and hip extension was measured to calculate the LPR and LHR. Paired, two-tailed t
      tests were used to compare the LS and hip ROM between the non-LBP and LBP groups,
      two-way repeated measures analysis of variance was used to compare time with the
      non-LBP and LBP groups for LHR, and linear prediction was used to describe the
      LPR. Results: The maximum LS ROM in the LBP group was significantly less than
      that in the non-LBP group by 6.6  degrees  (p = .005). There was no difference in
      the maximum hip ROM between the groups (p = .376). The LHR did not change during
      trunk extension (F [4, 428] = 1.840, p = .120), the mean LHR was 4.6 in the non
      LBP group and 3.7 in the LBP group, and there was no difference between the
      groups (p = .320). The linear function of the LPR indicated, that when the hip
      joint was extended by 1  degrees , the LS extended by 3.2  degrees  in the non
      LBP group (R2 = .997, p < .001) and 2.8  degrees  in the LBP group (R2 = .999, p
      < .001). Conclusion: LBP inhibited lumbar motion relative to hip extension as LPR
      was smaller in the LBP group than in the non-LBP group. However, there was no
      difference between the groups in LHR because inter-individual variability
      affected the LHR. Level of Evidence: 3b.

PMID- 30090676
TI  - RADIOGRAPHIC HIP OSTEOARTHRITIS IS PREVALENT, AND IS RELATED TO CAM DEFORMITY 12
      24 MONTHS POST-HIP ARTHROSCOPY.
AB  - Background: The prevalence of radiographic hip osteoarthritis (OA), and its
      relationship with outcomes after hip arthroscopy is unclear. Objectives: The aims
      of this study were to: (i) describe the prevalence of OA and cam deformity 12-24
      months post hip arthroscopy; (ii) to determine the association between
      radiographic OA and cam deformity, surgical and clinical findings and symptoms;
      and (iii) describe the differences between legs for radiological and clinical
      findings. Study Design: Cross sectional study. Methods: Seventy patients, mean
      age 36.7(range 18-59) years, 12-24 months post-arthroscopy. Main outcome
      measures: Outcomes were collected prospectively via clinical and radiographic
      examination. (i)Prevalence of OA and cam deformity measured on and
      anteroposterior pelvic radiographs; (ii)Hip disability and Osteoarthritis Outcome
      Score (HOOS) and International Hip Outcome Tool (iHOT-33) patient-reported
      outcomes (PROs); (iii)hip internal and external rotation range of motion (ROM).
      Associations between OA and surgical findings, PROs and clinical findings were
      determined using generalized estimated equations, between operated and non
      operated sides. Results: The prevalence of OA was 37%. The likelihood of OA 12-24
      months after surgery was positively associated with alpha angle size 12-24 months
      post-hip arthroscopy surgery (p=0.010). There were no differences between
      operated and non-operated legs in radiographic or clinical findings. Conclusion:
      Radiographic OA is prevalent in a population which has undergone hip arthroscopy.
      Increased OA severity is associated with a higher alpha angle 12-24 months post
      surgery. Level of evidence: Cross-sectional study Level IV.

PMID- 30090677
TI  - IMMEDIATE AND SHORT TERM EFFECT OF DRY NEEDLING ON TRICEPS SURAE RANGE OF MOTION
      AND FUNCTIONAL MOVEMENT: A RANDOMIZED TRIAL.
AB  - Background: Dry needling (DN) has been established as an effective treatment for
      myofascial pain, however, there are no studies thus far investigating the benefit
      to movement and motor control. Purpose: The primary purpose of this study was to
      compare differences in a series of outcomes between dry needling, dry needling
      and stretching, and stretching only in a sample of healthy males. A secondary
      purpose was to compare change over time. Design: Blinded, randomized controlled
      trial. Methods: Thirty healthy male subjects were randomly assigned to one of
      three intervention groups: DN, stretching, or combination DN +stretching.
      Subjects in the DN group and DN+stretch group received DN to a palpated trigger
      point (TrP) in the triceps surae to elicit local twitch response. Subjects in the
      stretch group and DN+stretch group were instructed in a home stretching program
      for gastrocnemius and soleus muscles. All groups were tested for dorsiflexion
      range of motion and performed functional tasks (overhead deep squat, and Y
      Balance test, Lower Quarter) prior to intervention, directly after intervention,
      and four days post intervention. Group comparisons were performed using a
      repeated measure Analysis of Variance and a partial eta squared calculation for
      effect size. For all measures a p-value of < 0.05 was used to determine
      significance. Cohen's criteria were used to categorize strength of effect size.
      Results: There were no statistically significant differences among groups for
      range of motion nor functional measures, with the exception of the deep squat.
      Proportionally, the DN group improved significantly in deep squat performance
      (p<0.01) compared to the other groups. Time oriented improvements were seen for
      the YBT posterior-lateral reach (p = 0.02) only. Between groups effect sizes
      ranged from 0.02 (small) to 0.17 (large). Conclusions: Including DN did not
      markedly influence range of motion nor functional assessment measures, excluding
      those seen during the overhead deep squat. Effect measures suggest the lack of
      significant findings may be an issue of statistical power. Level of Evidence: 1b.

PMID- 30090678
TI  - THE DEGREE OF TENDINOSIS IS RELATED TO SYMPTOM SEVERITY AND PHYSICAL ACTIVITY
      LEVELS IN PATIENTS WITH MIDPORTION ACHILLES TENDINOPATHY.
AB  - Background: Achilles tendinopathy negatively affects a person's ability to be
      physically active. However, remaining physically active during the rehabilitation
      process does not impact clinical outcomes when a pain-monitoring model is
      followed. There are several factors, such as the progression of pain and
      structural changes, kinesiophobia, functional impairments, or medical advice,
      which may explain why some patients become physically inactive while others
      maintain a physically active lifestyle. Purpose: The purposes of this study were
      1) to compare the clinical presentation of patients with Achilles tendinopathy
      with high and low activity levels 2) to examine the relationship between tendon
      thickening and symptom severity in patients with Achilles tendinopathy and 3) to
      determine the proportion of patients with Achilles tendinopathy who have a high
      degree of kinesiophobia and if this proportion differs based on activity level.
      Study Design: Cross-sectional. Methods: Fifty-three patients with Achilles
      tendinopathy were dichotomized into low activity (n=30) and high activity (n=23)
      groups based on their physical activity level. Patient characteristics, symptom
      severity, kinesiophobia, tendon thickening, and lower leg function were
      quantified and analyzed to test the study hypotheses. Results: Patients with low
      activity levels had greater tendon thickening and a larger body mass compared to
      patients with high activity levels. There were no differences in symptom
      severity, kinesiophobia, or lower leg function between groups. A negative
      relationship (r=-0.491; p<0.001) was found between tendon thickening and symptom
      severity. Thirty-eight percent of patients demonstrated a high degree of
      kinesiophobia, but the proportion did not differ between groups. Conclusion:
      Patients with Achilles tendinopathy who have low physical activity levels
      demonstrate greater tendinosis than patients who are highly active. These
      structural changes are negatively associated with symptom severity. However,
      symptom severity, kinesiophobia, and functional deficits do not differ between
      patients with different activity levels. Level of evidence: Level 3.

PMID- 30090679
TI  - A MECHANISM FOR LIGAMENTUM TERES INJURIES IN FEMOROACETABULAR IMPINGEMENT: AN
      ANATOMICAL STUDY.
AB  - Background: Femoroacetabular impingement can produce abnormal biomechanics that
      lead to compensatory injuries around the hip and pelvis. Ligamentum teres
      pathologies are commonly associated with these bony deformities but a mechanism
      for injury has not been described in the literature. Purpose: The purpose of this
      study was to describe a potential mechanism behind ligamentum teres injury and
      impingement between the femoral neck and acetabulum. Study Design: Laboratory
      controlled cadaveric study. Methods: Twenty-six hips from 15 embalmed cadavers (8
      male; 7 female) with lifespans between 55-93 years were skeletonized. The hip was
      placed in 90  degrees  flexion and 0  degrees  abduction/adduction and internally
      rotated until the femoral head neck contacted the acetabulum. This position of
      impingement with respect to internal rotation was recorded with a goniometer. The
      hip was then further internally rotated until end range of motion was achieved
      and again the position of internal rotation recorded with a goniometer. Results:
      The positions of internal rotation at which impingement occurred (mean 9  degrees
      ; SD 4.2; Range -2  degrees  to 15  degrees ) when compared to end range (mean 21
      degrees ; SD 5.7; Range 5  degrees  to 27  degrees ) were significantly
      different (p<0.005; t = 14.8). In all the hips, after impingement occurred the
      site of bony contact between the femoral neck and acetabulum acted as a pivot
      point. The femoral head was levered inferiorly with a loss of the rotational
      center within the acetabulum, as internal rotation continued. This movement of
      the femoral head caused the ligamentum teres to tighten and restricted further
      movement. Movement into internal rotation beyond this end position caused rupture
      of the ligamentum teres. Conclusion: Internal rotation range of motion can occur
      beyond the position of impingement and resulted in abnormal inferior movement of
      the femoral head and tightening of the ligament teres. This study provides
      cadaveric evidence for the mechanism of ligamentum teres injury in those with who
      engage in activities that required motion beyond the point of impingement.

PMID- 30090680
TI  - THE EFFECTS OF AN AQUATIC MANUAL THERAPY TECHNIQUE, AQUASTRETCHTM ON RECREATIONAL
      ATHLETES WITH LOWER EXTREMITY INJURIES.
AB  - Background: When paired together, manual therapy and exercise have been effective
      for regaining range of motion (ROM) in multiple conditions across varied
      populations. Although exercise in an aquatic environment is common, research
      investigating manual therapy in this environment is limited. There is little
      evidence on AquaStretchTM an aquatic manual therapy technique, but anecdotal
      clinical evidence suggests its effectiveness. Purpose: To investigate the effects
      of AquaStretchTM on ROM and function in recreational athletes with self-reported
      lower extremity injury and pain. Study Design: Quasi-experimental design.
      Methods: Injured recreational athletes participated in a 30-minute intervention
      session of AquaStretch.TM Injuries ranged from ankle (sprains and overuse), knee
      (contusions, sprains, and overuse), and hip conditions (contusions, overuse, and
      pain). Before a single intervention (preintervention) and within 24 hours after
      the intervention (postintervention), participants completed the following patient
      reported outcome instruments: the Lower Extremity Functional Scale (LEFS) and the
      Foot and Ankle Ability Measure (FAAM) Sports subscale. AROM measurements of the
      ankle, knee, and hip and the following muscle length tests were measured: Ober's
      test, measurement of the popliteal angle, and the modified Thomas test. Finally,
      the overhead deep squat test was performed as a test of function. Results: Twenty
      six recreational athletes with lower extremity injuries of the ankle, knee, and
      hip, aged 18-60 years (18 males, 8 females, mean age 27.4 years) completed the
      study. The overall group by time interaction for the mixed-model Generalized
      Estimating Equations analysis was statistically significant for the LEFS (all
      p<.002) and for the FAAM Sports subscale (p<.01). There were no statistically
      significant time (pre vs post) by group interactions for range of motion and
      other measures, including the Ober's test, the overhead deep squat test,
      popliteal angle, and the modified Thomas test for injured athletes. Conclusion:
      One session of AquaStretchTM in recreational athletes improved the patient-rated
      outcome measures of function specifically the LEFS and FAAM Sports subscale.
      These results suggest that AquaStretchTM may be an effective form of manual
      therapy to improve lower extremity function in injured athletes. Levels of
      Evidence: 2b, Individual Cohort Study.

PMID- 30090681
TI  - THE EFFECT OF TACKLING TRAINING ON HEAD ACCELERATIONS IN YOUTH AMERICAN FOOTBALL.
AB  - Background: Many organizations have introduced frameworks to reduce the incidence
      of football related concussions through proper equipment fitting, coach
      education, and alteration of tackling technique. Purpose: The purpose of this
      study was to examine the effects of training in a vertical, head up tackling
      style on the number of head accelerations experienced while tackling in a
      controlled laboratory situation. The authors hypothesized that training in a head
      up tackling technique would reduce the severity of head acceleration experienced
      by participants. Design: Controlled Laboratory Study. Methods: Twenty-four
      participants (11.5 +/- 0.6 years old, 60.5 +/- 2.2 in, 110 +/- 18.4 lbs.) with
      previous playing experience completed a one-day training session on tackling
      technique utilizing a tackling dummy. A subgroup of these participants completed
      an additional two days of training with a 48 hour retention test. Head
      accelerations were analyzed at baseline and end of training. Feedback consisted
      of verbal feedback utilizing the Qualitative Youth Tackling Scale (QYTS) and
      video tackling playback. Results: A significant reduction in the number of peak
      linear head accelerations over 10 g and peak rotational head accelerations over
      1885 deg/s2 were found in dummy tackling after training in both the one day and
      three day training regimens. A significant change in QYTS tackling form score was
      found between pretest and post-test (p = 0.004). Participants with larger steps
      had a 2.28, 4.42 and 4.14 increased odds ratio of sustaining head accelerations
      over 10, 15 and 20 g respectively. Conclusions: Training in a vertical, head up
      tackling style decreased the number of head accelerations over threshold values
      sustained while tackling; decreased step length may be the driving factor in the
      effectiveness of this tackling form. Level of Evidence: Level 3b.

PMID- 30090682
TI  - INTER-RATER AGREEMENT AND VALIDITY OF A TACKLING PERFORMANCE ASSESSMENT SCALE IN
      YOUTH AMERICAN FOOTBALL.
AB  - Background: Long term neurologic injury and concussion have been identified as
      risks from participation in American football. Altering tackling form has been
      recommended to reduce the risk of neurologic injury caused by head accelerations
      when tackling. The purpose of this research is to determine the inter-rater
      agreement and validity of the Qualitative Youth Tackling System (QYTS), a six
      item feedback scale to correct tackling form, when utilized by novice and expert
      raters. Hypothesis: Experienced raters will have higher levels of agreement with
      each other and with motion capture when compared to novice raters. Methods: Both
      novice and experienced raters viewed video of youth athletes (ages 9-13) tackling
      a dummy in a laboratory setting along. The raters identified successful
      performance according to a binary rating scale for each component. Analysis of
      both the raters' agreement with each other and with an objective motion capture
      measure were completed. Results: Fliess' Kappa measures between all raters were
      found to be moderate for head placement (k=.48), fair for cervical extension
      (k=.38), trunk inclination (k=.37), shoulder extension (k=.27) and step length
      (k=.29), and there was no agreement for pelvic height (k=.-16). When compared to
      the dichotomized validation measures of each of the five components provided by
      the motion capture system the average Cohen's Kappa agreement was substantial for
      pelvic height (k=.63), fair for step length (k=.34), cervical extension (k=.40),
      trunk inclination (k=.35), and slight for shoulder extension (k=.16). The
      experienced raters outperformed the novice raters in all categories. Conclusion:
      The results of this study indicate that skilled raters are better able to
      identify the movement patterns included in the QYTS when compared to a validation
      measure as well have higher rates of inter-rater agreement than novice raters.
      Level of Evidence: 3b.

PMID- 30090683
TI  - THE EFFECTS OF BLOOD FLOW RESTRICTION TRAINING ON FUNCTIONAL IMPROVEMENTS IN AN
      ACTIVE SINGLE SUBJECT WITH PARKINSON DISEASE.
AB  - Background: Blood flow restriction (BFR) applied during low intensity exercise
      produces hypertrophy and strength gains equivalent to traditional training.
      Previous research has shown the positive effects of BFR on younger and older
      adults. However, the effectiveness of BFR on subjects with Parkinson Disease (PD)
      has not been investigated. Hypotheses/Purpose: The purpose of the study was to
      determine the effects of BFR on a recreationally active person with PD in regards
      to functional improvements and safety. The hypothesis was that BFR training will
      demonstrate improvements in motor function, gait and endurance, while decreasing
      symptoms associated with Restless Leg Syndrome (RLS) in a subject with PD. Study
      Design: A single subject, B-A design was used. Methods: The subject was an active
      65-year-old male recreational boxer diagnosed with PD. Baseline data were
      measured on day one. The intervention (Phase B) consisted of five, two-minute
      bouts of walking on treadmill with lower extremity BFR cuffs interspersed with 1
      minute rest, three times a week for six weeks, at 0 grade incline, and speed of
      50 meters/min. The pressure increased from the initial 120 to 160 mmHg at the end
      of the phase B as per the subject's tolerance. A four-week baseline phase (A)
      without the BFR intervention followed phase B. The outcome measures which were
      measured every two weeks over the 10 weeks included: Timed Up and Go Test, 6
      Minute Walk Test, 30-Second Chair Stand Test, and the RLS Questionnaire. Results:
      All outcome measures steadily improved every two weeks during the six week
      intervention phase and steadily declined when the intervention was removed during
      the second four week baseline phase according to visual inspection of the graphed
      data points. Conclusion: The subject enjoyed and tolerated the intervention well
      without any adverse effects. The results were that BFR training can produce
      functional improvements, reduce restless leg syndrome symptoms and can be safely
      utilized with a subject with PD who wishes to maintain his ability to remain
      recreationally active.

PMID- 30090684
TI  - CLINICAL DECISION MAKING AND DIFFERENTIAL DIAGNOSIS IN A CYCLIST WITH UPPER
      QUARTER PAIN, NUMBNESS, AND WEAKNESS: A CASE REPORT.
AB  - Background and Purpose: Differentiating between cervical nerve root and
      peripheral nerve injuries can be challenging. A phenomenon known as double crush
      syndrome may increase the susceptibility to injury and symptoms at other
      locations along the course of the nerve. The purpose of this case report is to
      describe the physical therapy differential diagnosis and management of a cyclist
      with upper extremity pain, weakness, and paresthesia. Case Description: The
      subject was referred to physical therapy with a diagnosis of cervical disc
      disease. His chief complaints were chronic neck and right shoulder pain as well
      as a recent onset of right hand numbness and weakness following 100-mile bike
      ride one month prior. Diagnostic imaging revealed multi-level degenerative
      changes of the cervical spine. Initial electromyography and nerve conduction
      studies (EMG/NCS) indicated right ulnar neuropathy at the elbow. The ultimate
      incorporation of ulnar nerve mobilizations in various positions immediately
      decreased symptoms. In light of the subject's improvement after ulnar nerve
      mobilizations, imaging findings, and EMG/NCS findings, the subject's presentation
      was consistent with a double crush syndrome with C8 nerve root compression and
      distal ulnar nerve compression at the elbow. Outcomes: The subject demonstrated
      full resolution of all symptoms, 0% disability on the Neck Disability Index, 8.3%
      disability of the Disabilities of the Arm, Shoulder, and Hand questionnaire,
      normal EMG/NCV findings, and unrestricted return to work and endurance cycling at
      three months and maintained at one year. He did not require hand surgery.
      Discussion: This case report highlights the importance of continual clinical re
      examination and re-assessment with ancillary diagnostic testing, especially if
      chosen interventions are not eliciting desired responses. The identification of
      key risk factors, such as occupation and recreational activities is imperative in
      achieving the most efficacious clinical treatment. In this case, the recognition
      of a double crush syndrome assisted in optimizing the physical therapy plan of
      care and the subject ultimately achieving full recovery. Level of evidence: Level
      4.

PMID- 30090685
TI  - CLINICAL DECISION MAKING AND TREATMENT IN A RUNNER WITH HIP PAIN AND
      NEUROMUSCULAR CONTROL DYSFUNCTION: A CASE REPORT.
AB  - Background and Purpose: The incidence of running related injuries remains high
      despite numerous efforts to understand the mechanical contributors to the
      etiology of these injuries. In light of continued running injury, theories of
      neuromuscular control, or movement patterns, have been suggested as possible
      contributors to running related injuries. However, the clinical decision making
      determining when altered neuromuscular control strategies may be affecting a
      runner's symptoms has not been described. Therefore, the purpose of this case
      report is to describe the clinical reasoning within the ICF framework for a
      runner with hip pain and neuromuscular control dysfunction. Case Description: A
      47-year-old, experienced, female runner presented with posterior hip pain and
      radiating posterior thigh pain limiting her ability to participate in running and
      threatened her goal to run in an upcoming marathon. Several features of her
      examination indicated soft tissue muscular irritation of the posterior hip
      complex related to impaired balance and control of the lower quarter during
      functional movement and running activities consistent with a neuromuscular
      control dysfunction. Her initial Focus on Therapeutic Outcomes (FOTO) score was
      69 with predicted change score of +7. Outcomes: The subject was able to achieve
      her goals including a return to participation in her weekly running routine and
      competing in a marathon race. Objective examination features of range of motion,
      strength, and control of movement were all improved. Her reported function was
      greatly improved with a final FOTO score 98. Discussion: The diagnosis and
      treatment of running related injuries remains a clinical challenge. This case
      report describes the examination and clinical reasoning in diagnosing
      neuromuscular control dysfunction and proposes a treatment progression to address
      this functional limitation. The decision making scheme is also structured to
      follow the International Classification of Functioning, Disability, and Health.
      Level of evidence: 4.

PMID- 30090686
TI  - EVALUATING THE PROGRESS OF MID-PORTION ACHILLES TENDINOPATHY DURING
      REHABILITATION: A REVIEW OF OUTCOME MEASURES FOR SELF- REPORTED PAIN AND
      FUNCTION.
AB  - Introduction: Management of mid-portion Achilles tendinopathy is a challenge for
      both clinicians and researchers. Alteration in tendon structure, muscle
      performance and pain processing mechanisms have been suggested as mechanisms
      driving improvement in pain and function. However, few trials have used
      consistent outcome measures to track changes in pain and function. Objectives: 1)
      To identify all outcomes measures used in trials utilizing exercise-based
      interventions for mid-portion Achilles tendinopathy (AT) that assess self
      reported pain and function and to report on the reliability and validity of the
      identified measures, and 2) Propose measures to optimally assess self-reported
      pain and function in patients with AT. Design: Literature Review. Data Sources:
      Three major electronic databases were searched from inception until May 2016 for
      studies using isometric, eccentric or isotonic loading protocols for mid-portion
      AT. Eligibility Criteria: Randomized and non-randomized trials of isometric,
      eccentric or isotonic loading in people with mid-portion AT. Results: Forty-six
      studies were included and all outcome measures assessing self-reported pain and
      function were extracted. While a variety of outcome measures have been used, few
      have provided reliability data. There is evidence to suggest that the Victorian
      Institute of Sports Assessment- Achilles (VISA-A) is the only valid and reliable
      measure of self-reported pain and function for people with mid-portion AT. No
      other outcome measures have been validated in mid-portion AT. Conclusion: The
      VISA-A remains the gold standard for assessing pain and function in mid-portion
      AT. However, while the validity or reliability of the Numerical Rating Scale
      (NRS) of pain during a functional task has not been established it may be a
      better measure of immediate treatment effect. Level of evidence: 5.

PMID- 30090687
TI  - POST-OPERATIVE CRITERION BASED REHABILITATION OF ACL REPAIRS: A CLINICAL
      COMMENTARY.
AB  - : The anterior cruciate ligament (ACL) is the most commonly reconstructed
      ligament of the knee. Most often, the goal of surgical reconstruction is to
      recreate stability within the knee and prevent joint degeneration. To date,
      clinical studies have not demonstrated the ability of various reconstruction
      techniques in establishing complete knee stability when comparing rates of
      osteoarthritis. Rates of osteoarthritis commonly resemble those of knees which
      have not be reconstructed and in this light, may not demonstrate a successful
      outcome. As modern medicine continues to develop and in the understanding of
      underlying biological processes grows, some surgeons have turned their attention
      back to an ACL repair technique. The purpose of this clinical commentary is to
      discuss the parameters associated with a phase progression for an isolated ACL
      repair. Physiological healing time frames, along with objective clinical
      assessment, following a criterion-based progression is described in accordance
      with post-operative healing parameters to serve as a reference for a
      rehabilitation specialist. Level of evidence: 5.

PMID- 30090688
TI  - NONOPERATIVE TREATMENT FOR INJURIES TO THE IN-SEASON THROWING SHOULDER: A CURRENT
      CONCEPTS REVIEW WITH CLINICAL COMMENTARY.
AB  - : Repetitive overhead throwing generates tremendous demands on the shoulder joint
      of the overhead athlete. Clinicians, therapists, and medical staff are charged
      with optimizing a throwing athlete's shoulder mobility and stability to maximize
      performance and prevent injury. Modifiable risk factors such as strength
      asymmetry, glenohumeral range of motion deficits, and scapulothoracic joint
      abnormalities contribute to the overhead athlete's predisposition to shoulder
      injury. Most shoulder injuries in the overhead thrower can be successfully
      treated nonoperatively to allow in-season return to sport. The optimal
      rehabilitation program must be based on an accurate evaluation of historical and
      physical information as well as diagnostic imaging. Return to play decisions
      should be individualized and should weigh subjective assessments along with
      objective measurements of range of motion, strength, and function. The purpose of
      this clinical commentary is to summarize the current literature regarding the
      nonoperative treatment options for these common injuries, and to present a
      treatment plan to safely return these athletes to the field of play. Level of
      evidence: 5.

PMID- 30090689
TI  - The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Alzheimer's
      Disease.
AB  - Despite a wealth of knowledge gained in the past three decades concerning the
      molecular underpinnings of Alzheimer's disease (AD), progress towards obtaining
      effective, disease modifying therapies has proven to be challenging. In this
      manner, numerous clinical trials targeting the production, aggregation, and
      toxicity of beta-amyloid, have failed to meet efficacy standards. This puts into
      question the beta-amyloid hypothesis and suggests that additional treatment
      strategies should be explored. The recent emergence of CRISPR/Cas9 gene editing
      as a relatively straightforward, inexpensive, and precise system has led to an
      increased interest of applying this technique in AD. CRISPR/Cas9 gene editing can
      be used as a direct treatment approach or to help establish better animal models
      that more faithfully mimic human neurodegenerative diseases. In this manner, this
      technique has already shown promise in other neurological disorders, such as
      Huntington's disease. The purpose of this review is to examine the potential
      utility of CRISPR/Cas9 as a treatment option for AD by targeting specific genes
      including those that cause early-onset AD, as well as those that are significant
      risk factors for late-onset AD such as the apolipoprotein E4 (APOE4) gene.

PMID- 30090690
TI  - Synthesis and Chiral Separation of Fibratol, Isopropyl 2-(4-((4
      chlorophenyl)(hydroxyl) methyl)-phenoxy)-2-methylpropanoate.
AB  - Practical synthetic route for the formation of enantiomeric mixture of Isopropyl
      2-(4-((4-chlorophenyl)(hydroxyl)methyl)phenoxy)-2-methylpropanoate (Fibratol
      2a/b) from isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoate
      (Fenofibrate 1) has been developed. Method has also been established for the
      chiral separation of enantiomers of Fibratol 2a/b that is synthesized using the
      route mentioned above. The optical activity determined for enantiomerically
      separated Fibratol (2a) and Fibratol (2b) are -5.2 degrees  and 8.0 degrees 
      which reflect their ability to rotate plane polarized light counterclockwise
      (levo) and clockwise (dextro), respectively.

PMID- 30090691
TI  - IFN-gamma and IL-5 whole blood response directed against mycolactone polyketide
      synthase domains in patients with Mycobacterium ulcerans infection.
AB  - Background: Buruli ulcer is a disease of the skin and soft tissues caused by
      infection with a slow growing pathogen, Mycobacterium ulcerans. A vaccine for
      this disease is not available but M. ulcerans possesses a giant plasmid pMUM001
      that harbours the polyketide synthase (PKS) genes encoding a multi-enzyme complex
      needed for the production of its unique lipid toxin called mycolactone, which is
      central to the pathogenesis of Buruli ulcer. We have studied the immunogenicity
      of enzymatic domains in humans with M. ulcerans disease, their contacts, as well
      as non-endemic areas controls. Methods: Between March 2013 and August 2015,
      heparinized whole blood was obtained from patients confirmed with Buruli ulcer.
      The blood samples were diluted 1 in 10 in Roswell Park Memorial Institute (RPMI)
      medium and incubated for 5 days with recombinant mycolactone PKS domains and
      mycolyltransferase antigen 85A (Ag85A). Blood samples were obtained before and at
      completion of antibiotic treatment for 8 weeks and again 8 weeks after completion
      of treatment. Supernatants were assayed for interferon-gamma (IFN-gamma) and
      interleukin-5 (IL-5) by enzyme-linked immunosorbent assay. Responses were
      compared with those of contacts and non-endemic controls. Results: More than 80%
      of patients and contacts from endemic areas produced IFN-gamma in response to all
      the antigens except acyl carrier protein type 3 (ACP3) to which only 47% of
      active Buruli ulcer cases and 71% of contacts responded. The highest proportion
      of responders in cases and contacts was to load module ketosynthase domain
      (Ksalt) (100%) and enoylreductase (100%). Lower IL-5 responses were induced in a
      smaller proportion of patients ranging from 54% after ketoreductase type B
      stimulation to only 21% with ketosynthase type C (KS C). Among endemic area
      contacts, the, highest proportion was 73% responding to KS C and the lowest was
      40% responding to acyltransferase with acetate specificity type 2. Contacts of
      Buruli ulcer patients produced significantly higher IFN-gamma and IL-5 responses
      compared with those of patients to PKS domain antigens and to mycolyltransferase
      Ag85A of M. ulcerans. There was low or no response to all the antigens in non
      endemic areas controls. IFN-gamma and IL-5 responses of patients improved after
      treatment when compared to baseline results. Discussion: The major response to
      PKS antigen stimulation was IFN-gamma and the strongest responses were observed
      in healthy contacts of patients living in areas endemic for Buruli ulcer.
      Patients elicited lower responses than healthy contacts, possibly due to the
      immunosuppressive effect of mycolactone, but the responses were enhanced after
      antibiotic treatment. A vaccine made up of the most immunogenic PKS domains
      combined with the mycolyltransferase Ag85A warrants further investigation.

PMID- 30090692
TI  - Feeding regimen modulates zebrafish behavior.
AB  - Here we show that the feeding regimen modulates zebrafish (Danio rerio) behavior.
      With regard to the time elapsed between feeding and behavioral evaluation, fish
      fed 3 h before behavioral evaluation in the novel tank test (NTT) showed
      decreased activity and a trend toward an anxiolytic reaction (increased use of
      the upper section of the aquarium) in comparison to fish fed 0.5, 6, 12, 24 or 48
      h before testing, although differences were not statistically significant for all
      comparisons. Activity and use of the upper section of the aquarium did not differ
      significantly among the other treatments. Regarding feeding frequency, fish fed
      once a day showed higher anxiety-like behavior (decreased use of the upper
      section of the aquarium) in comparison to fish fed twice a day, but feeding four
      or six times per day or only every second day did not result in differences from
      feeding twice a day. Feeding frequency had no effect on activity level.
      Metabolically, fish fed once a day presented decreased levels of glucose and
      glycogen and increased lactate when compared to the regular feeding (fish fed
      twice a day), suggesting that feeding regimen may modulate carbohydrate
      metabolism. Mechanistically, we suggest that the metabolic changes caused by the
      feeding regimen may induce behavioral changes. Our results suggest that the high
      variability of the results among different laboratories might be related to
      different feeding protocols. Therefore, if issues pertaining to the feeding
      regimen are not considered during experiments with zebrafish, erroneous
      interpretations of datasets may occur.

PMID- 30090693
TI  - Causal inference with large-scale assessments in education from a Bayesian
      perspective: a review and synthesis.
AB  - This paper reviews recent research on causal inference with large-scale
      assessments in education from a Bayesian perspective. I begin by adopting the
      potential outcomes model of Rubin (J Educ Psychol 66:688-701, 1974) as a
      framework for causal inference that I argue is appropriate with large-scale
      educational assessments. I then discuss the elements of Bayesian inference
      arguing that methods and models of causal inference can benefit from the Bayesian
      approach to quantifying uncertainty. Next I outline one method of causal
      inference that I believe is fruitful for addressing causal questions with large
      scale educational assessments within the potential outcomes framework- namely,
      propensity score analysis. I then discuss the quantification of uncertainty in
      propensity score analysis through a Bayesian approach. Next, I discuss a series
      of necessary conditions for addressing causal questions with large-scale
      educational assessments. The paper closes with a discussion of the implications
      for the design of large-scale educational assessments when the goal is in asking
      causal questions and warranting causal claims.

PMID- 30090694
TI  - Candida dubliniensis abscess: A clinical case and a review of the literature.
AB  - Candida dubliniensis infections are rare in the absence of prolonged
      immunocompromised status or intravenous drug abuse. We present a case of a C.
      dubliniensis soft tissue abscess in a patient with uncontrolled diabetes as his
      only immunocompromising risk factor, treated with surgical drainage and medical
      management.

PMID- 30090695
TI  - All-trans-retinoic-acid and arsenic trioxide induced remission in promyelocytic
      blast crisis.
AB  - A 78-year-old-male with chronic myeloid leukemia (CML) treated for seven years
      with dasatinib developed an acute promyelocytic leukemia complicated by
      disseminated intravascular coagulopathy. A promyelocytic blast crisis was
      diagnosed by demonstrating co-expression of chimeric BCL/ABL and PML/RARalpha
      translocations by karyotyping, fluorescence in situ hybridization, and
      quantitative real-time polymerase chain reaction. Promyelocytic blast crisis of
      CML is a rare event with historically poor outcomes. Treatment of our patient
      with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) resulted in
      complete morphologic remission. We review here the relevant literature of
      promyelocytic blast crisis and highlight the potential of ATRA/ATO as first line
      management.

PMID- 30090696
TI  - Brain tissue pulsatility is related to clinical features of Parkinson's disease.
AB  - Introduction: This study investigated whether brain tissue pulsatility is
      associated with features of disease severity in Parkinson's disease (PD).
      Methods: Data were extracted from the Parkinson's Progression Markers Initiative
      among 81 adults with PD (confirmed with DATSCANTM). Brain tissue pulsatility was
      computed using resting state blood oxygenation level dependent (BOLD) MRI in
      white matter (WM), referred to as BOLDTP. Motor impairment was assessed using the
      Movement Disorders Society unified Parkinson's disease rating scale. Factor
      analysis generated composite scores for cognition and vascular risk burden. A
      linear regression model examined the association of BOLDTP with age, sex, motor
      impairment, cognition, vascular risk burden and PD duration. In addition, we
      investigated whether BOLDTP relates to WM hyperintensity (WMH) volume, WM
      fractional anisotropy (WM-FA) and striatal binding ratio (SBR) of dopamine
      transporter. Results: Motor impairment (t = 2.3, p = .02), vascular burden (t =
      2.4, p = .02) and male sex (t = 3.0, p = .003) were independently associated with
      BOLDTP (r2 = 0.40, p < .001). BOLDTP was correlated with WMH volume (r = 0.22, p
      = .05) but not WM-FA nor SBR (p > .1). In addition, BOLDTP (t = 2.76, p = .008)
      and SBR (t = -2.04, p = .04) were independently related to motor impairment (r2 =
      0.18, p = .006). Conclusion: Our findings show that brain tissue pulsatility from
      BOLD images in WM is related to neurological and vascular features in PD. BOLDTP
      may be useful in PD to study small vessel alterations that appear distinct from
      WM structural changes.

PMID- 30090697
TI  - Changes in electrophysiological markers of cognitive control after administration
      of galantamine.
AB  - The healthy brain is able to maintain a stable balance between bottom-up sensory
      processing and top-down cognitive control. The neurotransmitter acetylcholine
      plays a substantial role in this. Disruption of this balance could contribute to
      symptoms occurring in psychosis, including subtle disruption of motor control and
      aberrant appropriation of salience to external stimuli; however the pathological
      mechanisms are poorly understood. On account of the role beta oscillations play
      in mediating cognitive control, investigation of beta oscillations is potentially
      informative about such mechanisms. Here, we used magnetoencephalography to
      investigate the effect of the acetylcholinesterase-inhibitor, galantamine, on
      beta oscillations within the sensorimotor region during both a sensorimotor task
      and a relevance-modulation task in healthy participants, employing a double blind
      randomized placebo controlled cross-over design. In the galantamine condition, we
      found a significant reduction in the post-movement beta rebound in the case of
      executed movements and also in a planned but not executed movement. In the latter
      case, the effect was significantly greater following task-relevant compared with
      irrelevant stimuli. The results suggest that the action of galantamine reduces
      the influence of top-down cognitive processing relative to bottom-up perceptual
      processing in a manner resembling changes previously reported in schizophrenia.

PMID- 30090698
TI  - Complex spatial and temporally defined myelin and axonal degeneration in
      Huntington disease.
AB  - Although much prior work has focused on the basal ganglia and cortical pathology
      that defines Huntington's disease (HD), recent studies have also begun to
      characterize cerebral white matter damage (Rosas et al., 2006; Dumas et al.,
      2012; Poudel et al., 2014). In this study, we investigated differences in the
      large fascicular bundles of the cerebral white matter of gene-positive HD
      carriers, including pre-manifest individuals and early symptomatic patients,
      using recently developed diffusion tractography procedures. We examined eighteen
      major fiber bundles in 37 patients with early HD (average age 55.2 +/- 11.5, 14
      male, 23 female), 31 gene-positive, motor negative pre-symptomatic HD (PHD)
      (average age 48.1 +/- 11.5, 13 male, 18 female), and 38 healthy age-matched
      controls (average age 55.7 +/- 8.6, 14 male, 24 female), using the TRActs
      Constrained by UnderLying Anatomy (TRACULA) procedure available as part of the
      FreeSurfer image processing software package. We calculated the mean fractional
      anisotropy (FA) and the mean radial (RD) and axial diffusivities (AD) for each
      fiber bundle. We also evaluated the relationships between diffusion measures,
      cognition and regional cortical thinning. We found that early changes in RD of
      select tracts in PHD subjects were associated with impaired performance on
      neuropsychological tests, suggesting that early changes in myelin might underlie
      early cognitive dysfunction. Finally, we found that increases in AD of select
      tracts were associated with regionally select cortical thinning of areas known to
      atrophy in HD, including the sensorimotor, supramarginal and fusiform gyrus,
      suggesting that AD may be reflecting pyramidal cell degeneration in HD. Together,
      these results suggest that white matter microstructural changes in HD reflect a
      complex, clinically relevant and dynamic process.

PMID- 30090699
TI  - Long-term use of methylphenidate in a boy with hypothalamic tumor, drug-resistant
      epilepsy and ADHD.
AB  - *We report the successful treatment of a boy with hypothalamic tumor, gelastic
      seizures, drug-resistant epilepsy and ADHD*The use of methylphenidate
      significantly reduced symptoms of ADHD while seizure frequency remained
      unchanged.

PMID- 30090700
TI  - Renal artery fibromuscular dysplasia in Pompe disease: A case report.
AB  - Vascular involvement in Late Onset Pompe Disease, glycogen storage disease type
      II characterized by limb-girdle muscle and diaphragmatic weakness, is well
      documented. Abnormalities of posterior cerebral circulation have mostly been
      reported, whereas there are also cases of associated extracerebral arteriopathy.
      We report the case of a 42-year-old man diagnosed with LOPD a year after renal
      infarct due to renal artery fibromuscular dysplasia. We propose that the
      association of LOPD and arteriopathy should always be considered in clinical
      practice.

PMID- 30090701
TI  - Suspicion of mitochondrial disease remains frequently unconfirmed after whole
      exome sequencing.

PMID- 30090702
TI  - Combining genotypic and phenotypic analyses on single mutant zebrafish larvae.
AB  - Zebrafish is a powerful animal model used to study vertebrate embryogenesis,
      organ development and diseases (Gut et al., 2017) [1]. The usefulness of the
      model was established as a result of various large forward genetic screens
      identifying mutants in almost every organ or cell type (Driever et al., 1996;
      Haffter et al., 1996) [[2], [3]]. More recently, the advent of genome editing
      methodologies, including TALENs (Sander et al., 2011) [4] and the CRISPR/Cas9
      technology (Hwang et al., 2013) [5], led to an increase in the production of
      zebrafish mutants. A number of these mutations are homozygous lethal at the
      embryonic or larval stages preventing the generation of homozygous mutant
      zebrafish lines. Here, we present a method allowing both genotyping and phenotype
      analyses of mutant zebrafish larvae from heterozygous zebrafish incrosses. The
      procedure is based on the genotyping of the larval tail after transection,
      whereas phenotypic studies are performed on the anterior part of the zebrafish
      larvae. *The method includes (i) a protocol for genotyping, (ii) protocols for
      paraffin embedding and histological analyses, (iii) protocols for protein and
      histone extraction and characterization by Western blot, (iv) protocols for RNA
      extraction and characterization by RT-PCR, and (v) protocols to study caudal
      spinal cord regeneration.*The technique is optimized in order to be applied on
      single zebrafish embryos and larvae.

PMID- 30090703
TI  - A methodological approach to the air-sea energy fluxes data collection and
      analysis at the tropical coastal ocean.
AB  - The southern South China coastal oceans within the South East Asian region are
      much lacking in the perception of the surface energy budget and evaporation over
      the ocean waters in response to climatic changes. The eddy covariance method was
      used to measure the energy fluxes, microclimate variables, and surface water
      temperature from November 2015 to October 2017 at the Straits of Malacca, South
      China Sea; Pulau Pinang, Malaysia, situated at latitude 5 degrees 28'06"N, and
      longitude 100 degrees 12'01"E. This work focused on the methodological approach
      to the air-sea energy fluxes data collection and analysis. In this regard, the
      method applied for the direct measurements and analysis of energy fluxes and
      other meteorological parameters in the site is considered and reported. *The
      paper summarizes the analysis of energy fluxes, microclimate variables, and
      surface water temperature data in a tropical coastal ocean station using the eddy
      covariance method.*The methodological approach illustrates the method of analysis
      applied in this study which can be compared and used for similar studies in other
      places.*The reproducible data analysis technique matches similar comparative
      methods such as Matlab and Python.

PMID- 30090704
TI  - Assessment of toxic elements in sediments of Linggi River using NAA and ICP-MS
      techniques.
AB  - Fourteen sediment samples were collected along Linggi River, Malaysia. Neutron
      activation analysis (NAA) and inductively coupled plasma-mass spectrometry (ICP
      MS) techniques were used in the determination of toxic element contents. The
      results showed that As, Cd and Sb concentrations were higher at all sampling
      stations, with enrichment factor values ranging from 17.7 to 75.0, 2.1 to 19.5
      and 6.6 to 28.4, respectively. Elements of Pb and Zn) were also enriched at most
      of the sampling stations whilst Cu, Cr and Ni were shown as background levels.
      The sediment of Linggi River can be categorised as low (<8.0) to very high degree
      of contamination (>32.0). The mean concentrations of elements viz. Cd, Cr, Ni,
      Pb, Sb and Zn were lower than the threshold effect level (TEL) of FSQGs values
      except for As. The concentration of As (arsenic) was higher than PEL and PEC of
      FSQGs values.

PMID- 30090705
TI  - Validation of the VitalPAC Early Warning Score at the Intermediate Care Unit.
AB  - AIM: To assess the performance and clinical relevance of the Early Warning
      Scoring (EWS) system at the Intermediate Care Unit (IMCU). METHODS: This cohort
      study used all the VitalPAC EWS (ViEWS) scores collected during each nursing
      shift from 2014 through 2016 at the mixed surgical IMCU of an academic teaching
      hospital. Clinical deterioration defined as transfer to the Intensive Care Unit
      (ICU) or mortality within 24 h was the primary outcome of interest. RESULTS: A
      total of 9113 aggregated ViEWS scores were obtained from 2113 admissions. The
      incidence of the combined outcome was 272 (3.0%). The area under the curve of the
      ViEWS was 0.72 (CI: 0.69-0.75). Using a threshold value of six, the sensitivity
      was 68% with a positive predictive value of 5% and a number needed to trigger
      (e.g., false alarms) of 19%. CONCLUSION: The ViEWS at the IMCU has a
      discriminative performance that is considerably lower than at the hospital ward.
      The number of false alarms is high, which may result in alarm fatigue. Therefore,
      use of the ViEWS in its current form at the IMCU should be reconsidered.

PMID- 30090706
TI  - Role of narrow band ultra violet radiation as an add-on therapy in peritoneal
      dialysis patients with refractory uremic pruritus.
AB  - AIM: To assess the role of narrow band ultraviolet B (UVB) as a treatment option
      in peritoneal dialysis patients with refractory uremic pruritus. METHODS: In this
      retrospective study, 29 adult patients with end stage renal failure on peritoneal
      dialysis, and who had refractory uremic pruritus, were given narrow band UVB
      radiation as an add-on therapy to standard care for a duration of 12 wk. The
      response to the pruritus was assessed both weekly and at the end of the study
      period using a visual analogue score (VAS). RESULTS: The average VAS score at the
      end of the study was 3.14 +/- 1.59, which was significant compared to the
      baseline value of 7.75 +/- 1.02 (P < 0.05). Improvements in symptoms were noted
      in 19 out of 21 (90.4%) patients. However, relapse occurred in six out of the 19
      patients who responded. The dropout rate was high during the study period
      (33.3%). CONCLUSION: Narrow band UVB is effective as an add-on therapy in
      peritoneal dialysis patients with refractory uremic pruritus. However, the
      present regime is cumbersome and patient compliance is poor.

PMID- 30090707
TI  - Case of human immunodeficiency virus infection presenting as a tip variant of
      focal segmental glomerulosclerosis: A case report and review of the literature.
AB  - The incidence of the collapsing variant of focal segmental glomerulosclerosis
      (FSGS) as a human immunodeficiency virus (HIV)-associated nephropathy has reduced
      since the introduction of antiretroviral therapy (ART). However, the incidence of
      other variants of FSGS, except for the collapsing variant, is increasing, and its
      therapeutic strategies remain uncertain. A 60-year-old HIV infected man in
      remission with ART was admitted for progressive renal insufficiency and nephrotic
      ranged proteinuria. Renal biopsy revealed a tip variant of FSGS and his clinical
      manifestations resolved with corticosteroid therapy. HIV infected patients might
      develop non-collapsing FSGS, including tip variant of FSGS and corticosteroid
      therapy might be effective for them. A renal biopsy might be essential to
      determine the renal histology and to decide on corticosteroid therapy.

PMID- 30090708
TI  - Professional medical writing support: The need of the day.

PMID- 30090709
TI  - My 40-year journey in diabetes research: The power of collaboration.
AB  - This article describes a 40 year journey in diabetes research of an Indian
      diabetologist, starting as an undergraduate medical student. The article
      describes how collaborations with multiple stake-holders is necessary if one is
      to advance one's research from the simple studies that one starts with and take
      it to higher and higher levels. It is also essential that the seeds for doing
      research are planted early in a medico's life even during undergraduate days, as
      only then will more doctors take up medical research as a career. Finally, the
      article demonstrates how it is possible to do good quality research in India if
      one has the passion and sustained interest in the field even if one is not in a
      university or academic setup.

PMID- 30090710
TI  - An analysis of completeness and quality of adverse drug reaction reports at an
      adverse drug reaction monitoring centre in Western India.
AB  - Purpose/Aim: The Adverse Drug Reaction [ADR] form is the source document for the
      Pharmacovigilance Programme of India [PvPI] and captures information first hand
      from the patient. The raw data from it then gets converted into an individual
      case safety report [ICSR] after entry into Vigiflow. The National Coordinating
      Centre [NCC] uses an instrument to assess quality of these ICSRs. We carried out
      the present study to assess whether the same instrument with minor modifications
      could be used to check the quality of ADR forms at our centre. Materials and
      Methods: ADR reports of three months from three consecutive years were selected
      randomly. The ADR form [18 fields] was matched with the NCC instrument [14
      fields] as the latter is made from the former. A perfect ICSR would score 1.
      Three fields in the NCC instrument - case narrative, compliance with standard
      operating procedures [SOPs] and free text [5 components] were modified, while the
      rest were retained. Zero was given to the first two fields. In the third field,
      we retained only 3/5 components and changed the last two components [sender and
      reporter comments] to dechallenge and rechallenge while keeping the total score
      the same. Results: A total of 1008 ADR reports were analyzed. We found an overall
      completeness score of approximately 80% with the lowest completeness score being
      for the year 2015. The mandatory fields had close to 100% scores. Conclusion: The
      NCC instrument was found well suited to evaluate quality and completeness of ADR
      forms.

PMID- 30090711
TI  - Knowledge and attitudes of Indian surgeons regarding professional medical writing
      support.
AB  - Aim: The number of scientific papers published from India each year is low. We
      tried to determine how often Indian surgeons publish in biomedical journals,
      challenges preventing them from publishing more often, their awareness of the
      international guidelines that acknowledge professional medical writing as an
      ethical service, and their willingness to hire medical writers for their
      publications. Materials and Methods: A convenience sample of 100 of the surgeons
      attending a national conference were explained about the survey and asked to
      complete a survey questionnaire. All results were expressed as absolute
      frequencies and percentages. Results: Of the 81 who responded, 43 (53%) had never
      published. Only 31/81 (38%) had published in the last 5 years. The challenges
      preventing more frequent publication were reported to be the lack of support for
      carrying out statistical analyses (58%), lack of time (41%), lack of sufficient
      data (38%), and lack of support for literature search (37%). Twenty-two (27%)
      surgeons were aware that they could hire a professional medical writer (PMW), 26
      (32%) knew that the International Committee of Medical Journal Editors allowed
      PMWs to contribute to articles published in the biomedical journals, 75 (93%)
      were interested in hiring medical writers or to consider it in the future. Only 6
      (7.4%) showed no such interest. Conclusion: There was poor awareness and great
      interest in hiring PMWs. It might be beneficial to increase the awareness of
      clinicians about the scientific expertise and communication skills of PMWs and
      how they can add value to biomedical publications.

PMID- 30090712
TI  - Drug prescription pattern of outpatients in a tertiary care teaching hospital in
      Tamil Nadu.
AB  - Purpose: Drug use prescribing indicators advocated by the World Health
      Organization (WHO) are important tools for assessing the degree of polypharmacy,
      use of generic medicines, and to evaluate if there is inappropriate use of
      antibiotics or parenteral medications besides estimating the adherence to the
      essential drugs list. This study aimed to assess the WHO prescribing indicators
      in prescriptions given at the medical outpatient department (OPD) in a private
      medical college hospital in South India. Materials and Methods: The study was
      done prospectively from patients when they presented for consultation at the
      medical OPD at our tertiary care center. Prescriptions were randomly chosen to be
      analyzed for the WHO prescribing indicators from September 2016 to April 2017.
      Results: A total of 700 prescriptions were analyzed and the average number of
      drugs per prescription was 2.955 +/- 1.32. 32.57% of prescriptions had fixed drug
      combinations and a similar value of 36% was obtained for prescriptions containing
      more than one drug for the same indication. Amongst the prescribing indicators,
      generic prescribing was appallingly low (6.42%). In contrast, antibiotic
      prescribing and prescription of injections showed an appreciably rational trend
      with 15.42% and 8.14%, respectively. Furthermore, the prescription of the drugs
      enlisted in the essential drugs list was determined to be 90.67%. Discussion: The
      need for increase in generic prescribing and augmenting the adherence of
      prescriptions to the essential drugs list has been identified. This can be
      accomplished by multimodal approach that includes regulatory changes, conducting
      educational programs directed at attitudinal change among current doctors and
      imparting modifications in medical curriculum so as to inculcate the culture of
      abiding by the best prescription practices among budding doctors. Conclusion:
      This study has delineated the requisite for pertinent changes in current
      prescribing trends in a tertiary care teaching private colleges.

PMID- 30090713
TI  - Polypharmacy and comorbidity status in the treatment of type 2 diabetic patients
      attending a tertiary care hospital: An observational and questionnaire-based
      study.
AB  - Purpose/Aim: Diabetes mellitus is associated with several comorbid conditions.
      Thus, often, diabetic patients are prescribed multiple drugs. Although multiple
      drugs help to combat various diseases, they also increase the propensity of drug
      interactions and adverse drug reactions. The present study thus tried to evaluate
      the comorbid conditions and concurrent medications associated with type 2
      diabetic patients. It also aimed to address patient compliance for the
      medications provided to them. Materials and Methods: This was a cross-sectional
      observational study conducted for 2 months - January-February 2017. Data were
      collected from prescriptions of the patients and also by interviewing the willing
      patients, attending the Diabetic Clinic of R. G. Kar Medical College, Kolkata,
      India. Results: During the study period, 150 patients were interviewed and their
      prescriptions were studied. Out of 150 patients, 69 (46%) were males and 81 (54%)
      were females. The mean age of the study population was 51.5 (+/-0.78) years. The
      present study evaluated that 83.3% (125) of the study population suffered from at
      least one comorbid conditions, the most common being hyperlipidemia (70.7%) and
      hypertension (47.3%). The average number of drugs prescribed is 4.72 (+/-0.11)
      per prescription. Metformin was prescribed to 96% of the patients. The concurrent
      medications recommended included hypolipidemics (72%), antihypertensives (68%),
      drugs for peptic ulcer (34.7%), and antiplatelets (10.7%). Conclusion: The
      present study thus concluded that diabetic patients suffer from a number of
      comorbid conditions, most commonly, cardiovascular problems. The comorbidity
      increased with the age. The level of polypharmacy was also high, thereby
      increasing the pill burden for the patients.

PMID- 30090714
TI  - Understanding diagnostic tests - Part 3: Receiver operating characteristic
      curves.
AB  - In the previous two articles in this series on biostatistics, we examined the
      properties of diagnostic tests and various measures of their performance in
      clinical practice. These performance measures vary according to the cutoff used
      to distinguish the diseased and the healthy. We conclude the series on diagnostic
      tests by looking at receiver operating characteristic curves, a technique to
      assess the performance of a test across several different cutoffs, and discuss
      how to determine an optimum cutoff.

PMID- 30090715
TI  - Indian Regulatory Update: January - March 2018.

PMID- 30090716
TI  - Plagiarism: Either intentional or unintentional, it is still plagiarism!

PMID- 30090717
TI  - The Changing Face of Primary Hyperparathyroidism.

PMID- 30090718
TI  - Lean Metabolic Syndrome: An Emerging Concept.

PMID- 30090719
TI  - Lean Metabolic Syndrome: A Concept or a Reality?
AB  - Aims and Objectives: Metabolic syndrome (MetS) is fairly common in India.
      International Diabetes Federation (IDF) has defined it as the presence of central
      obesity with region/ethnicity-specific waist circumference as a mandatory
      defining criterion along with the presence of two other features from
      dysglycemia, systolic and/or diastolic hypertension, hypertriglyceridemia, and
      low high-density lipoprotein. Although obesity is not prevalent in rural parts of
      India, especially among the underprivileged population, other individual
      components of the syndrome are not infrequent among these lean/nonobese persons.
      In this study, we evaluated the prevalence of MetS in rural West Bengal. We also
      examined that if those persons above the recommended cutoff for waist are
      excluded, and thus only lean/nonobese persons are included, and the same
      definition of MetS (herein termed as lean MetS) is applied (three out of four
      criteria), what will be the prevalence of MetS and will it be lower in the
      nontribal population compared to the tribal population? Materials and Methods: A
      population-based study was done in the rural area of West Bengal comprising 200
      peoples from scheduled tribe (ST) population and 205 people from the neighborhood
      community from non-ST population to compare the metabolic health with respect to
      anthropologic and biochemical parameters. Results: The prevalence of MetS from
      rural areas of West Bengal was found to be 21.48% as per IDF criterion, but
      applying NCEP ATP III criteria, the overall prevalence of MetS rose to 31.1%. The
      prevalence of normal waist/lean MetS was 12.8%, and there was no significant
      difference between nontribals versus tribal cohort (14.6% of the nontribes versus
      11.6% of the tribal cohort, P = 0.436). Conclusion: A significant number of
      persons with nonobese/lean MetS exist in the rural area. We suggest that if
      region-specific waist criteria are not satisfied, the diagnosis should still be
      sorted by NCEP ATP III criteria.

PMID- 30090720
TI  - Neuroendocrine Neoplasms in Rare Locations: Clinicopathological Features and
      Review of the Literature.
AB  - Introduction: Neuroendocrine tumors (NETs) occur more often in lungs,
      gastrointestinal tract, or pancreas. Data about terminology and grading of NETs
      in rare locations are scarce and variable, and they have been reported mainly as
      case reports. Materials and Methods: We here describe our experience with NETs in
      unusual locations. We have reviewed all NETs diagnosed in our institution and
      summarized their clinicopathological features. We have also reviewed the
      literature and discussed the main characteristics of NETs in each site. Results:
      Two hundred and forty-three primary NETs were diagnosed. About 55.2% of patients
      were men and the mean age was 62 years. About 90.7% of NETs were located in
      lungs, gastrointestinal tract, or pancreas, and 50.8% of them were low-grade
      tumors. We identified 13 NETs in rare locations: breast, ovary, endometrium,
      vulva, uterine cervix, extrahepatic biliary tract, kidney, sinonasal tract, and
      thymus. Three additional tumors were diagnosed by the senior author in other
      institution. Patients were asymptomatic or presented with nonspecific symptoms.
      All NETs were treated with surgery and 31% of patients received adjuvant therapy.
      There were 10 Grade 3 (62.5%), 2 Grade 2 (12.5%), and 4 Grade 1 (25%) tumors.
      Mean follow-up was 72 months. About 60% of G3 tumors recurred or progressed. G2
      tumors were located in breast, and both patients are stable. About 50% of G1
      tumors recurred or progressed (both renal NETs). Conclusions: NETs in rare
      locations are heterogeneous, and their behavior does not seem to correlate
      absolutely with tumor grade. More studies are needed to clarify the role of
      proliferation rate in these tumors.

PMID- 30090721
TI  - Correlation of Thyroid Hormone Profile with Biochemical Markers of Renal Function
      in Patients with Undialyzed Chronic Kidney Disease.
AB  - Objective: The present study was conducted to evaluate the correlation of renal
      functions with thyroid hormone levels in patients with undialyzed chronic kidney
      disease (CKD). Literature shows significant alteration in thyroid hormone
      function tests in CKD patients who are receiving long-standing dialysis
      treatment. However, not much is described in those receiving conservative
      management without dialysis. Although CKD is associated with an increased
      prevalence of primary hypothyroidism, various studies on thyroid hormone status
      in uremic patients have reported conflicting results. Methodology: Thyroid
      hormone levels and biochemical markers of renal function were estimated in 30
      undialyzed CKD patients and similar number of age- and sex-matched healthy
      controls, followed by statistical analysis and correlation. Results: Free
      triiodothyronine (FT3) and free thyroxine (FT4) were found to be significantly
      reduced (P < 0.001 for each) in undialyzed CKD patients whereas thyroid
      stimulating hormone (TSH) levels showed statistically insignificant alteration in
      both groups. We also observed that urea and creatinine were negatively correlated
      whereas creatinine clearance was positively correlated with both FT3 and FT4
      having high statistical (two tailed) significance with P < 0.001. Nonsignificant
      correlation was seen between blood urea and TSH (r = 0.236, P = 0.069),
      creatinine clearance, and TSH (r = 0.206, P = 0.114 Pearson's correlation
      coefficient). There is just significant positive correlation between the serum
      creatinine values and TSH (r = 0.248, P = 0.049). Conclusions: Thyroid hormones
      were significantly decreased in undialyzed CKD patients as compared to healthy
      controls.

PMID- 30090722
TI  - Study of Visceral and Subcutaneous Abdominal Fat Thickness and Its Correlation
      with Cardiometabolic Risk Factors and Hormonal Parameters in Polycystic Ovary
      Syndrome.
AB  - Aim of the Study: This study aimed to compare the different adiposity parameters,
      namely visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT)
      between patients with polycystic ovary syndrome (PCOS) and controls. In addition,
      it aimed to correlate these adiposity indices with hormonal parameters as well as
      cardiovascular (CV) risk factors in patients with PCOS. Materials and Methods:
      Newly diagnosed PCOS patients of reproductive age group according to Rotterdam
      criteria were included. Age- and body mass index (BMI)-matched healthy females
      with normal menstrual cycles were taken as controls. All the study participants
      underwent detailed clinical, biochemical, and hormonal evaluation. Transabdominal
      ultrasound (US) was performed for detailed ovary imaging and assessment of
      adiposity (SAT and VAT) parameters. Results: A total of 58 PCOS patients and 40
      age- and BMI-matched controls were included. PCOS patients had significantly
      higher levels of androgens (P < 0.001), elevated highly sensitive C-reactive
      protein (P = 0.007), and higher degree of insulin resistance (P < 0.001) than
      controls. PCOS patients had a mean SAT of 2.37 +/- 0.7 cm and mean VAT of 8.65 +/
      1.78 cm. These parameters were significantly higher than controls who had a mean
      SAT of 2.01 +/- 0.7 cm (P = 0.014) and mean VAT of 7.4 +/- 1.89 cm (P = 0.003),
      despite both groups having similar BMI. Among PCOS cohort, VAT correlated
      positively with total testosterone (r = 0.295, P = 0.025) and negatively with
      dehydroepiandrosterone sulfate (r = -0.210, P = 0.114). However, no significant
      correlation was observed between SAT and androgens in PCOS group. Conclusion:
      PCOS patients, whether obese or nonobese, had elevated visceral adiposity than
      controls. VAT correlated positively with adverse CV risk factors and testosterone
      in PCOS patients. Hence, a simple and inexpensive ultrasonography screening of
      visceral fat may identify women who have adverse metabolic profile and enhanced
      CV risk.

PMID- 30090723
TI  - Sex hormone Profile in Human Immunodeficiency Virus-Infected Men and It's
      Correlation with CD4 Cell Counts.
AB  - Background: In human immunodeficiency virus (HIV)-infected men, hypogonadism is
      the most common endocrinological disorder, and most cases of hypogonadism are
      secondary. The aim of this study was to find out the hormonal abnormalities in
      HIV-infected males and it's correlation with CD4 cell counts. Materials and
      Methods: One hundred HIV-infected male patients were evaluated in the Department
      of Medicine, Postgraduate Institute of Medical Education and Research and Dr. Ram
      Manohar Lohia Hospital, New Delhi, India, over a period of 12 months from
      September 2014 to August 2015 using history, physical examination, routine
      baseline investigations, and CD4 counts. Free testosterone,
      dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle
      stimulating hormone (FSH), and prolactin were measured using an overnight fasting
      sample. Patients were divided into three groups on the basis of CD4 counts (Group
      A: CD4 counts >=350/mm3, Group B: CD4 counts between 200 and 349/mm3, and Group
      C: CD4 counts <200/mm3). Data were analyzed using Student's t-test, ANOVA test,
      Chi-square test, and Pearson's test and P <= 0.05 was considered statistically
      significant. Results: In 100 HIV-infected males, overall prevalence of
      hypogonadism was found to be 66%, and 30%-35% patients had symptoms of
      hypoandrogenemia. Hypogonadotropic hypogonadism was found in 42% of patients. A
      significant association (P = 0.027) was found between prevalence of hypogonadism
      and the level of immunodeficiency with an increase in the prevalence of
      hypogonadism as CD4 counts decreased. Lower levels of free testosterone and DHEAS
      were found in cases of severe immunosuppression with a statistically significant
      correlation with CD4 counts. Correlation of other sex hormones (LH, FSH, and
      prolactin) with CD4 counts not statistically significant. Mean free testosterone
      and FSH were found to be significantly higher in patients on antiretroviral
      therapy (ART) than in those not on ART (P = 0.028 and P = 0.045, respectively),
      but no specific ART drug or their drug combination was found to have a
      significant correlation with levels of any sex hormone. Conclusion: Hypogonadism
      (hypogonadotropic hypogonadism) was found to be a common endocrinological
      disorder in HIV-infected male population, seen more commonly in association with
      low CD4 counts.

PMID- 30090724
TI  - Impairment of Health-related Quality of Life among Indian Patients with
      Hypothyroidism.
AB  - Context: Health-related quality of life (HRQL) is an important outcome measure
      for various diseases, although there are sparse data regarding HRQL among Indian
      patients with hypothyroidism. Aims: This study aimed to assess HRQL among Indian
      patients with hypothyroidism using the SF-36 questionnaire. Methods: This cross
      sectional study evaluated 244 consecutive patients with hypothyroidism who were
      treated at the Vydehi Institute of Medical Sciences and Research Centre in
      Bengaluru. All patients were >18 years old and visited the outpatient department
      for endocrine treatment. Perceived health status was evaluated using the SF-36
      questionnaire. The patients' data were compared to data from 250 age-matched and
      sex-matched healthy controls. Results: Compared to the healthy controls, the
      patients with hypothyroidism had significantly lower scores for six of the eight
      SF-36 scales. No significant intergroup differences were observed in the "role
      emotional" and "social functioning" dimensions. Interpretation and Conclusions:
      Hypothyroidism was associated with reduced HRQL among Indian patients. These
      patients generally experienced greater reductions in physical dimensions,
      compared to social and emotional dimensions.

PMID- 30090725
TI  - Molecular Profiling of Follicular Variant of Papillary Thyroid Cancer Reveals Low
      Risk Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear
      Features: A Paradigm Shift to Reduce Aggressive Treatment of Indolent Tumors.
AB  - Introduction: Encapsulated follicular variant of papillary thyroid carcinoma
      (EFVPTC) has been reclassified into noninvasive follicular thyroid neoplasm with
      papillary-like nuclear features (NIFTP) and invasive EFVPTC. NIFTP is considered
      a low-risk neoplasm. Therefore, follicular variant of papillary thyroid cancer
      (FVPTC) presently has two distinct histopathological subtypes - invasive EFVPTC
      and infiltrative/diffuse FVPTC. Molecular characteristics of these groups remain
      unclear. Methodology: Thirty FVPTCs (10 NIFTPs, 12 invasive EFVPTCs, and 8
      infiltrative/diffuse variants) were reviewed and screened for BRAF and RAS
      mutations by restriction fragment length morphism-polymerase chain reaction (PCR)
      and Sanger sequencing. The mRNA expression levels of iodine-metabolizing genes
      were analyzed using real-time PCR. The mutations status and mRNA expression
      levels were correlated with clinicopathological features. Results: All 10 NIFTPs
      had predominant follicular pattern. One case showed NRAS mutation, whereas none
      showed BRAF mutation. All invasive EFVPTC had capsular and/or lymphovascular
      invasion and 4/12 showed lymph node metastasis. BRAF and NRAS were seen in three
      cases each of invasive FVPTC. All eight infiltrating/diffuse FVPTCs showed
      infiltration into adjacent thyroid parenchyma and lymph node metastasis.
      Conclusion: BRAF mutation was observed in 62.5% of cases; however, no NRAS
      mutation was found. Sodium iodide symporter (NIS) expressions in NIFTP were
      similar to that of normal thyroid tissue, whereas it was downregulated in
      invasive and infiltrative/diffuse FVPTC. Our study supports the argument that
      NIFTP can be considered as low-risk follicular thyroid neoplasm. Those tumors
      that harbor BRAF mutations may be offered a complete thyroidectomy because they
      show decreased expression of NIS gene which confers a tendency to lose
      radioactive iodine avidity and further recurrence of the tumor.

PMID- 30090726
TI  - Neck Circumference to Height Ratio is a Reliable Predictor of Liver Stiffness and
      Nonalcoholic Fatty Liver Disease in Prediabetes.
AB  - Background and Objectives: Nonalcoholic fatty liver disease (NAFLD) and
      dysglycemia are public health challenges. There is urgent need for anthropometric
      surrogates for NAFLD screening. This study evaluated role of neck circumference
      (NC) and neck-height ratio (NHtR) as predictors of liver stiffness measure (LSM)
      in individuals with prediabetes (IPD). Methods: In a cross-sectional study, 188
      IPD from 1130 screened individuals underwent anthropometry, ultrasonography,
      Fibroscan(r) for LSM, dyslipidemia, insulin resistance (IR), and fetuin-A
      assessment. Results: Hypertension, hypertriglyceridemia, low high-density
      lipoprotein cholesterol (HDL-C), metabolic syndrome (MetS), NAFLD, and
      significant liver stiffness (SLS) (LSM >8.5kPa) were observed in 53.7%, 31.4%,
      71.3%, 73.9%, 24.5%, and 11.2% prediabetes individuals, respectively. Prediabetes
      with NAFLD had significantly higher body mass index (BMI), NC, NHtR, glycated
      hemoglobin, triglycerides, fatty liver index (FLI), and LSM. Prediabetes in
      highest NHtR quartile had significantly higher BMI, hypertension, MetS, fasting
      glucose, glycated hemoglobin, homeostatic model assessment-IR, NAFLD, LSM, SLS,
      and lower HDL-C. Stepwise forward linear regression revealed that NHtR, FLI, and
      LDL-C were best predictors of LSM, at baseline (Model-1), after adjusting for age
      and sex (Model-2), and adjusting model-2 plus systolic and diastolic blood
      pressure (Model-3). NHtR and NC (in females) and NHtR and BMI (in males) had
      largest area under the curves for predicting LSM, NAFLD, and MetS. NHtR >=21.54
      cm/m (sensitivity: 90%; specificity: 52.5%; females) and >=21.62 cm/m
      (sensitivity: 80%; specificity: 49.4%; males) was best predictor of SLS.
      Interpretation and Conclusion: NHtR is a reliable tool for community screening of
      NAFLD and liver stiffness in prediabetes.

PMID- 30090727
TI  - Five-year Retrospective Study on Primary Hyperparathyroidism in South India:
      Emerging Roles of Minimally Invasive Parathyroidectomy and Preoperative
      Localization with Methionine Positron Emission Tomography-Computed Tomography
      Scan.
AB  - Background: Primary hyperparathyroidism (PHPT) is a common endocrine disease with
      a variable clinical presentation. PHPT is usually symptomatic at presentation in
      majority of the patients, especially in developing countries. As the
      accessibility to investigations, advanced imaging methods and surgical procedures
      are improving, the clinical profile of the patients with PHPT has undergone a
      palpable change compared to the earlier description. Hence we decided to look for
      a change in clinical, imaging and surgical outcomes of PHPT patients from South
      India. Methods: We collected the data on clinical presentation, biochemistry,
      radiological features and operative findings of patients with PHPT treated in our
      hospital from 2011-2015. Cases of PHPT were identified from the laboratory values
      using the biochemical criteria, after the exclusion of secondary and tertiary
      hyperparathyroidism cases. Results: Our study identified 54 patients (19 males
      and 35 females) with age ranging from 16 to 71 years. A Significant
      proportion(38.9%) of the patients were asymptomatic. Musculoskeletal symptoms
      (40.7%), renal manifestations (27.7%) and gastrointestinal system involvement
      (27.7%) constituted the other common modes of presentation. CNS involvement was
      seen in 3 patients. A palpable nodule in the neck was detected in 4 patients.
      Interestingly 4 patients were managed for parathyroid crisis at presentation.
      Biochemical features included hypercalcaemia (100%) and hypophosphatemia (59%)
      with a mean intact PTH level of 602.0+/-721.3 pg/ml. Sensitivity of
      Ultrasonography and Tc99M Sestamibi was 72% and 70.6% respectively for detecting
      a parathyroid adenoma. Sensitivity of C11 methionine PET-CT was 71.4% in those
      patients who were negative for other imaging modalities. Forty three patients
      (79.6%) underwent minimally invasive parathyroidectomy. Conclusion: In South
      India we have a notable change in the clinical presentation of PHPT from a
      symptomatic to an asymptomatic state. C11 Methionine PET - CT is an emerging
      modality for preoperative localisation especially when other imaging modalities
      are negative and when a minimally invasive parathyroidectomy is desired.

PMID- 30090728
TI  - The Impact of Uniform Capsular Dissection Technique of Total Thyroidectomy on
      Postoperative Complications: An Experience of More Than 1000 Total
      Thyroidectomies from an Endocrine Surgery Training Centre in North India.
AB  - Background: Total thyroidectomy (TT) with a uniform technique of capsular
      dissection (CD) is the preferred technique worldwide. The aim of study is to
      analyze the impact of uniform technique of CD for done as primary surgery at an
      endocrine surgery training centre. Patients and Methods: Retrospective review
      from 1995 to 2009. Data collected from hospital records and follow-up. Results:
      One thousand and thirty-eight cases were included, with mean age 42.91 +/- 13.48
      years; male:female - 1:2.2; mean duration of goiter - 99.83 +/- 105.1 months;
      67.8% were euthyroid and 30.7% - hyperthyroid at initial presentation; 35.5% were
      malignant. Surgery includes TT alone - 77.7% and TT with lymph nodes dissection -
      22.3%; sternotomy required in 1.2% and thoracotomy in 0.1%; tracheomalacia
      present in 3.9%; however, tracheostomy required in 4.5% and parathyroid
      autotransplantation in 21%; Peroperative mean gross gland weight was 124.34 +/-
      129.85 g. Complications include hypocalcemia (temporary - 35.9%; permanent -
      1.3%); recurrent laryngeal nerve palsy (temporary - 2.7%; permanent - 91%);
      hemorrhage - 1.3%; and various others. Conclusion: TT with uniform technique of
      CD is a safe procedure. Certain risk factors may predispose to complications,
      which can be avoided and managed adequately if anticipated beforehand.

PMID- 30090729
TI  - Paget's Disease of Bone: An Entity Still Exists in India.
AB  - Background: Paget's disease of bone (PDB) is uncommonly reported from India. We
      attempted to study the clinical and imaging features and management of
      participants who presented with PDB. Materials and Methods: In this retrospective
      study, clinical and imaging profile, biochemistry, and treatment outcomes of
      participants with PDB (n = 48) were obtained. Results: The mean age was 60 +/-
      11.3 years and 35% were women. Twenty percent were asymptomatic. Many (87%) had
      polyostotic involvement. Sixty percent (n = 29) underwent treatment with
      zoledronic acid and rest with oral bisphosphonates, and all achieved remission.
      Conclusion: Most of the pagetic participants had polyostotic disease and one
      fifth were asymptomatic. All participants had disease remission following
      treatment.

PMID- 30090730
TI  - Prevalence of Pediatric Metabolic Syndrome and Associated Risk Factors among
      School-Age Children of 10-16 Years Living in District Shimla, Himachal Pradesh,
      India.
AB  - Introduction: Recently, an increasing trend in the prevalence of pediatric
      metabolic syndrome (PMS) among school-age children has been documented in
      different parts of India. There is lack of data on the prevalence of PMS and its
      associated risk factors among school-age children living in district Shimla,
      Himachal Pradesh. Hence, to fill in the gap in the existing knowledge, the
      present study was conducted. Methodology: A cross-sectional study was conducted
      during 2015-2016. Thirty clusters (schools) were identified from a list of all
      schools using population proportionate to size sampling methodology. From each
      school, 70 children in the age group of 10-16 years were selected. Data was
      collected on the sociodemographic characteristics, anthropometry, waist
      circumference, blood pressure, and physical activity. Fasting venous blood
      samples were collected for estimation of blood glucose, triglycerides, and high
      density lipoprotein levels. Results: The prevalence of PMS using International
      Diabetes Federation classification was 3.3% and using modified-adult treatment
      panel classification criteria was 3.5%. Risk factors identified to be associated
      with PMS among school-age children were (i) male gender, (ii) high family monthly
      income, (iii) sedentary lifestyle, (iv) consumption of evening snack, (v)
      television/computer viewing, and (vi) motorized transportation for commuting to
      school. Conclusion: The PMS prevalence was 3.3% in school-age children residing
      in District Shimla. There is a need to formulate interventions to prevent and
      correct metabolic syndrome among them for reducing early onset of cardiovascular
      disease during adulthood.

PMID- 30090731
TI  - The Incidence of Hypoglycemia among Insulin-Treated Patients with Type 1 or Type
      2 Diabetes: Bangladeshi Cohort of International Operations-Hypoglycemia
      Assessment Tool Study.
AB  - Objectives: The objective of this study was to assess the incidence of
      hypoglycemia in patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes
      mellitus (T2DM) in Bangladeshi cohort of the International Operations
      Hypoglycemia Assessment Tool study. Materials and Methods: Patients diagnosed
      with either T1DM or T2DM, aged >=18 years, treated with insulin (any regimen) for
      >12 months, and completed self-assessment questionnaires (SAQs) to record
      demography, treatment information, and hypoglycemia during the 6-month
      retrospective and 4-week prospective periods (a total of 7 months) were enrolled
      in the study. Results: A total of 1179 patients were enrolled and completed the
      SAQ1 (T1DM, n = 25; T2DM, n = 1154). Almost all patients (T1DM: 100.0% [95%
      confidence interval (CI): 86.3%, 100.0%] and T2DM: 97.0% [95% CI: 95.9%, 97.9%])
      experienced at least 1 hypoglycemic event prospectively. The estimated rates of
      any and severe hypoglycemia were 26.6 (95% CI: 19.8, 35.0) and 14.1 (95% CI: 9.3,
      20.4) events per patient-per year (PPY), respectively, for patients with T1DM and
      18.3 (95% CI: 17.4, 19.2) and 12.1 (95% CI: 11.4, 12.9) events PPY, respectively,
      for patients with T2DM during the prospective period. At baseline, mean glycated
      hemoglobin (HbA1c) (+/-standard deviation) was 8.1 (+/-1.8%) for T1DM and 8.8 (+/
      1.8%) for T2DM. Hypoglycemic rate was independent of HbA1c levels and types of
      insulin. Conclusions: This is the first patient dataset of self-reported
      hypoglycemia in Bangladesh; results confirm that hypoglycemia is underreported.

PMID- 30090732
TI  - Prognostic Value of Thyroid Profile in Critical Care Condition.
AB  - Background: Patients suffering from critical illness admitted to the Intensive
      Care Unit (ICU) exhibit alterations in their thyroid hormone levels, collectively
      termed as euthyroid sick syndrome or nonthyroidal illness syndrome. Our study was
      conducted to determine the correlation between these changes in thyroid hormone
      levels and the prognosis of ICU-admitted patients. Methods: A total of 270 ICU
      admitted patients without previous history of thyroid disorder were included in
      the study. We recorded their baseline characteristics, acute physiology and
      chronic health evaluation (APACHE-II) score, thyroid hormone levels, lactate, and
      other parameters on admission. ICU mortality was the primary outcome. We analyzed
      the ability of each parameter to predict mortality in the participants. Further,
      we also evaluated whether the combination of thyroid hormone levels with APACHE
      II score could improve the mortality prediction. Results: The mean age of the
      study population was 38.99 +/- 18.32 years. A total of 81 patients (30%) expired
      during their ICU treatment. Both fT3 and fT4 levels were lower in nonsurvivors
      compared to survivors. Among the thyroid hormones, fT3 had the highest predictive
      value for ICU mortality, as seen by the largest area under the curve (AUC) value
      (0.990 +/- 0.007) which was even greater than AUC of APACHE-II score (0.824 +/-
      0.051) and fT4 (0.917 +/- 0.049). Univariate logistic regression analysis showed
      that fT3 (beta = 140.560) had the highest predictive potential for ICU mortality
      compared with APACHE-II score (beta = 0.776), fT4 (beta = 17.62) and other
      parameters. Multivariate logistic regression analysis revealed that the
      combination of fT3 and APACHE-II (R2 = 0.652) was superior in predicting
      mortality than APACHE-II alone (R2 = 0.286). Conclusion: We observed that fT3 was
      the strongest predictor of ICU mortality compared to all other parameters
      included in our study. Further, the combination of fT3 levels and APACHE-II
      scores provided for a higher probability for predicting mortality in ICU
      patients.

PMID- 30090733
TI  - Preoperative Preparation of Hyperthyroidism for Thyroidectomy - Role of
      Supersaturated Iodine and Lithium Carbonate.
AB  - Introduction: Thyroidectomy is effective and safe procedure for permanent cure of
      hyperthyroidism (HT). Iodine preparations are widely used before operation to
      prevent excess blood loss. Ideal regimen for refractory HT is debated. This
      retrospective case-control study is designed to study the efficacy of various
      regimens of preoperative preparations. Materials and Methods: Case records,
      anesthesia charts, and follow-up details of hyperthyroid patients undergoing
      thyroidectomy were reviewed and compared with an age- and sex-matched euthyroid
      patients operated during the same period. Iodine preparations were not used for
      preoperative preparation. Study group was subdivided based on preoperative
      regimens of anti-thyroid medications. Results: Of the 168 patients in the study
      group, procedure time, duration of hospital stay, and overall complication rate
      were high compared to euthyroid group. Operative blood loss was not high in the
      study group. There was no difference in rate of complications in the subgroups of
      the study cohort. Conclusion: Iodine preparations are not mandatory in
      preoperative preparation of HT. Lithium carbonate is effective in preoperative
      preparation of refractory HT. Rate of postthyroidectomy complications is not
      different in patients receiving thionamides alone or in combination with beta
      blocker.

PMID- 30090734
TI  - Etiological Search and Epidemiological Profile in Patients Presenting with
      Hypokalemic Paresis: An Observational Study.
AB  - Introduction: Hypokalemia is associated with increased morbidity and at times
      mortality. "Hypokalemic paralysis", particularly if recurrent, has often been
      considered synonymous with "hypokalemic periodic paralysis (HPP)"; however,
      diseases such as Gitelman syndrome (GS), Bartter syndrome (BS), and renal tubular
      acidosis (RTA) can have identical presentation. We have tried to explore the
      etiological spectrum along with epidemiological and certain clinical,
      biochemical, and electrophysiological features in patients with hypokalemic
      paralysis. Materials and Methods: In this observational study, 200 appropriate
      patients with hypokalemic paralysis (serum K+ <3.5 mmol/L) were evaluated for
      transcellular shift, extra-renal or renal loss of K+ as the underlying etiology
      of hypokalemia. We took urinary potassium >25 mmol/day as the cutoff for
      inappropriate renal loss of potassium in presence of hypokalemia. Serum and
      urinary osmolality along with arterial blood gas analysis were performed in all
      patients with renal loss of potassium. Serum and urinary sodium, potassium,
      calcium, magnesium, chloride, and creatinine were measured in normotensive
      patients with metabolic alkalosis. Hypertensive patients were evaluated with
      plasma aldosterone and renin activity. Results: Probable GS topped the list
      involving 28% individuals of the entire cohort while probable BS, distal RTA, and
      HPP were diagnosed in 20%, 22%, and 19% cases, respectively. Rural tribal
      population (61%) and age group of 30-40 years suffered the most (48%) with
      concentration of cases in hot and humid summer months. Conclusions: We suggest
      that patients with hypokalemic paresis should be evaluated thoroughly to unmask
      the underlying etiology that may have a different therapeutic and prognostic
      connotations and not to use the term "periodic" in cases of recurrent hypokalemic
      paralysis.

PMID- 30090735
TI  - A Comparison of Clinicopathological Characteristics and Short-Term Outcome of
      Papillary Thyroid Carcinoma with Tall Cell Histology and Classic Papillary
      Thyroid Carcinoma: A Single-Institution Experience.
AB  - Context: Papillary thyroid carcinoma with tall cell histology (PTC-TCH) is an
      aggressive subtype in terms of clinicopathological features and outcome. Even 10%
      of tall cells can show aggressive features. Aims: The aim of this study is to
      investigate the behavior of PTC-TCH, to compare with classic PTC (cPTC), and
      evaluate the short-term outcome. Settings and Design: This is a retrospective
      analysis of patients with cPTC and those with TCH (PTC-TCH) seen from January
      2010 to May 2017 seen in our Thyroid Cancer Clinic. Materials and Methods: A
      total of 40 patients with TCH were compared with 352 cPTC and evaluated for age,
      gender, tumor size, presence of multifocality, capsular, vascular invasion,
      extrathyroid extension, and appearance of metastases. Short-term response to
      therapy was assessed using the 2015 American Thyroid Association guidelines.
      Statistical Analysis: P < 0.05 was considered statistically significant. All
      analyses were performed with SPSS software (Version 21.0, Chicago, IL, USA).
      Results: PTC with TCH presented at a younger age, had larger tumors, and more
      extrathyroid extension. Seven out of 40 cases developed lung metastases, (17.5%
      vs. 4.5% in cPTC), within a year of diagnosis. Conclusion: PTC-TCH irrespective
      of percentage of tall cells showed aggressive features and early metastases. They
      should be recognized early as an aggressive subtype and treated intensively.
      Close follow-up must be instituted to look for metastases, especially to the
      lungs.

PMID- 30090736
TI  - Intraoperative Parathyroid Hormone Monitoring in Guiding Adequate
      Parathyroidectomy.
AB  - Background: Parathyroidectomy has been traditionally performed through bilateral
      neck exploration (BNE). However, with the use of intraoperative parathyroid
      hormone (IOPTH) assay along with preoperative localization studies, focused
      parathyroidectomy can be performed with good surgical success rate,
      multiglandular disease can be predicted, and hence recurrence and surgical
      failure can be prevented. Furthermore, it predicts eucalcemia in the
      postoperative period. The aim of this study was to evaluate the usefulness of
      IOPTH assay in guiding adequate parathyroidectomy in patients of primary
      hyperparathyroidism. Materials and Methods: Between year 2015 and 2017, 45
      patients of primary hyperparathyroidism underwent parathyroidectomy with IOPTH
      assay employed as an intraoperative tool to guide the surgical procedure. Blood
      samples were collected: (1) at preincision time, (2) preexcision of gland, (3) 5
      min postexcision of gland, and (4) 10-min postexcision of gland. On the basis of
      the Irvin criterion, an intraoperative PTH drop >50% from the highest either
      preincision or preexcision level after parathyroid excision was considered a
      surgical success. Otherwise, BNE was performed and search for other parathyroid
      glands done. Results: Ten-min postexcision PTH levels dropped >50% in 34 (75.6%)
      patients. True positive among them were 31 (68.8%), true negative 8 (17.7%),
      false positive 3 (6.6%), and false negative 3 (6.6%). We performed focused
      exploration at the outset in 40 (88.9%) patients and bilateral exploration for
      five patients as guided by preoperative localizing studies. Hence, IOPTH was
      helpful in guiding further exploration in 8 (17.7%) patients and prevented
      further exploration in 32 (71.1%) patients and also was able to predict
      eucalcemia in 97.7% patients at 6 months. Thus, IOPTH was able to obviate or to
      ask for additional procedure in 88.8% of patients. However, in three (6.6%)
      patients, IOPTH would guide unnecessary exploration and in equally, that is,
      three (6.6%) patients may require reoperation for unidentified parathyroids.
      Conclusion: IOPTH in adjunct with other localizing studies is very helpful for
      carrying out successful parathyroidectomy in uniglandular disease and predicting
      postoperative eucalcemia. However, more importantly, its role is valuable in
      equivocal imaging, in such cases, it prevents unnecessary exploration or helps in
      adequate parathyroidectomy.

PMID- 30090737
TI  - Incidence of Congenital Hypothyroidism in Western Rajasthan Using Cord Blood
      Thyroid-stimulating Hormone Levels as a Screening Tool: A Cross-sectional
      Hospital-based Study.
AB  - Background: Congenital hypothyroidism (CH) is considered the most common
      preventable cause of intellectual impairment, with a worldwide annual incidence
      of 1:4000 live births. In the absence of screening program actual incidence in
      India is not exactly known, but in previous studies it varies from 1:500 to
      1:3400. We wished to find out the incidence of CH in Western Rajasthan using cord
      blood TSH as a screening tool and venous TSH within 14 days of life as a
      confirmatory test. Methods: This cross sectional descriptive study was conducted
      over a period of six months in teaching hospitals attached to Medical College.
      Cord blood TSH value of 20 mIU/L or >20 mIU/L was taken as cut off for screening
      and all screen positive neonates were re-tested for serum TSH by taking venous
      samples within 14 days of life. Repeat TSH levels of 20mIU/L or more tested by
      Enzyme Linked Fluorescent Assay were considered confirmatory. Results: Total 9558
      cord blood samples were analyzed for TSH levels, out of which 533 came out to be
      screen positive (recall rate 5.57%). Out of these 58 could not be confirmed, so
      were excluded from the further analysis. Effective sample size and screen
      positive cases dropped to 9500 and 475 respectively, and out of these 13 were
      confirmed as CH (incidence - 1.37 per thousand live births). Conclusions:
      Considering the previous studies, incidence of CH is much higher in Western
      Rajasthan than the anticipated. Overall in India CH seems to be more prevalent
      than the other parts of the world, necessitating the need of national screening
      program.

PMID- 30090738
TI  - Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus.
AB  - Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD)
      commonly exist together. It has been regarded as a manifestation of the metabolic
      syndrome. The presentations of NAFLD range from simple steatosis (NAFL),
      nonalcoholic steatohepatitis (NASH), and cirrhosis. NAFLD has a prevalence of 70%
      among T2DM patients. Overweight/obesity and insulin resistance (IR) have been
      strongly linked with NAFLD. Noninvasive assessment and staging of disease are
      based on clinical parameters such as age, sex, liver function test, platelet
      count, lipid profile, BMI, and imaging modalities such as USG, transient
      elastography (TE), and magnetic resonance imaging mass spectroscopy. Such
      clinical scoring systems and TE are useful in the early detection of NAFLD and
      predicting fibrosis. The principle behind the management of NAFLD with T2DM
      involves an indirect effect through improvement in IR and glycemia and thus is
      used for the treatment of T2DM as well.

PMID- 30090739
TI  - Temporal Change in Profile of Association between Diabetes, Obesity, and Age of
      Onset in Urban India: A Brief Report and Review of Literature.
AB  - Context: Indian population is known to develop diabetes at lower body mass index
      (BMI) and younger age than their western counterparts. However, data on the
      prevalence of overweight/obesity in people with diabetes have not been well
      documented in the Indian literature. The current study also establishes time
      trends for the age of onset of diabetes mellitus type 2 in Urban India. Aims: The
      aim of this study was to analyze the current trend in the presentation of people
      with diabetes in a metropolitan city (Urban residents) in context to age, sex,
      and BMI. Settings and Design: Retrospective cross-sectional study. Subjects and
      Methods: Data captured in clinic electronic medical records from May 2015 to
      March 2017 are analyzed. The profile of newly diagnosed diabetes is also
      presented. Statistical Analysis Used: Data were analyzed descriptively and for
      statistical analysis, SPSS software was used. Results: A total of 1473 patients
      with age 52.6 +/- 12.7 (mean +/- standard deviation) and BMI of 27.86 +/- 4.83
      kg/m2 were analyzed. About 17.6% were overweight; 71.5% were obese. The
      significant higher proportion of females was overweight/obese (91.2% vs. 82% of
      males; P < 0.0001). Females had significantly higher mean BMI than males (29.19
      +/- 4.99 vs. 26.93 +/- 4.83; P <= 0.001). Overall, mean HbA1c of patients was
      7.84% +/-1.61% with no significant difference between genders. However, there was
      no difference in mean HbA1c based on either gender or BMI category. Among people
      with new-onset diabetes, there was even higher proportion of people with BMI >=23
      kg/m2 (overall 89.1%, males 87.6%, and females 91.6%). About 43.8% of people
      presented at <40 years age. Totally, 49.5% of males presented at age <40 years as
      compared to 33.9% of females. Conclusions: The prevalence of obesity among people
      with diabetes in Indian setting is now as high as in western studies. Indians are
      now presenting with diabetes at even earlier age with higher BMI.

PMID- 30090740
TI  - Flummoxed by Diamox.

PMID- 30090741
TI  - Pontine Myelinolysis as the Presenting Complication of Type 2 Diabetes Mellitus.

PMID- 30090742
TI  - Unmasking of Neuropsychiatric Manifestations after Total Thyroidectomy for
      Graves' Disease.

PMID- 30090743
TI  - Menses without Uterus.

PMID- 30090745
TI  - Cases of thallium intoxication in Syria: A diagnostic and a therapeutic
      challenge.
AB  - In mid-March 2015, a mother and her teenage daughter and son from Syria presented
      to a Syrian American Medical Society (SAMS) refugee clinic in the Beqaa Valley in
      Lebanon with the chief complaints of hair loss together with weakness and
      numbness of their lower extremities. They reported that on March 1, a military
      foe of their relative had given him several boxes of Middle Eastern cookies which
      were consumed by over 20 members of their families and neighbors. Soon after the
      consumption, most members of the households developed symptoms including
      abdominal pain, nausea, vomiting, and constipation. Later, many of the affected
      individuals, including the three who presented to the clinic, had pain and
      weakness in the extremities, skin lesions, and hair loss. Two subjects died
      inside Syria of kidney failure. In this report, we describe the diagnostic
      challenges faced until the arrival to the diagnosis of thallium intoxication and
      the therapeutic obstacles to getting adequate therapy. We also report the results
      of a survey sent to all subjects in the affected households and discuss the
      context of lawlessness that led to this intoxication and perhaps other cases.

PMID- 30090744
TI  - Prophylactic mastectomy for the prevention of breast cancer: Review of the
      literature.
AB  - The high incidence and recurrence rate of breast cancer has influenced multiple
      strategies such as early detection with imaging, chemoprevention and surgical
      interventions that serve as preventive measures for women at high risk.
      Prophylactic mastectomy is one of the growing strategies of breast cancer risk
      reduction that is of a special importance for breast cancer gene mutation
      carriers. Women with personal history of cancerous breast lesions may consider
      ipsilateral or contralateral mastectomy as well. Existing data showed that
      mastectomy effectively reduces breast cancer risk. However, careful risk
      estimation is necessary to wisely select individuals who will benefit from
      preventing breast cancer.

PMID- 30090746
TI  - Qat-induced intestinal obstruction: A case series of a new entity.
AB  - Background: Qat-induced intestinal obstruction is an acute manifestation of qat
      chewing which was not described previously in the literature. The aim of this
      case series is to describe the clinical presentation, the diagnostic and
      therapeutic measures, and the course of the disease. Methods: This retrospective
      case series included all patients who presented with qat-induced intestinal
      obstruction between July 1, 2013, and December 31, 2015. Results: The study
      included seven patients (five males and two females). The mean age was 41.4 years
      (22-60 years). All patients presented after 8-12 h of prolonged qat chewing with
      abdominal pain, severe abdominal distension, and inability to pass stool.
      Laboratory results were normal apart from slight leukocytosis (<15 * 109/L) in
      three patients. All patients showed air-fluid levels on the erect abdominal X
      ray. The management included intravenous fluids and symptomatic therapy. The
      symptoms resolved in 1-2 days and the follow-up after 1 week showed no residual
      complaints. Conclusions: Qat-induced intestinal obstruction is associated with
      the heavy and prolonged consumption of qat. The presentation mimics acute
      intestinal obstruction, but the course is benign. Spontaneous resolution with
      supportive inpatient treatment is the rule.

PMID- 30090747
TI  - Evaluating the efficacy of best practice alerts to improve Clostridium difficile
      early detection in hospital settings: A 6-month interim analysis of the 2-year
      prospective study.
AB  - Introduction: Clostridium difficile infection (CDI) is a leading cause of
      hospital-associated gastrointestinal illness with high burden on the health-care
      system. Design: Observational, retrospective, prospective, pre- and post
      intervention study on the incidence and prevalence rates of CDIs. The primary
      outcome is the healthcare-onset CDIs (HO-CDIs) incidence rate and proportion.
      Methods: Best practice alerts (BPAs) for CDI were developed in electronic medical
      records and released on July 13, 2016. When high-risk patients for CDI are
      identified, BPAs are triggered requiring nurses to order contact isolation and
      stool studies followed by other subsequent BPAs encouraging providers to de
      escalate antibiotics and order probiotics. Data on admission count, patient-days,
      CDIs categories prevalence, and incidence rates were collected for the 24-month
      preintervention and will be collected for the 24-month postintervention period.
      Results: An interim analysis comparing the data from the first 6-month
      postintervention period with the average 6-month data of the preintervention
      period showed that short-term BPAs use is associated with significant increase in
      the overall CDI infection rate (71.47 vs. 38.38, P < 0.0001), incidence rate
      (53.81 vs. 28.76, P < 0.0001), overall prevalence rate (1.86 vs. 1.32, P =
      0.001), and admission prevalence rate (1.10 vs. 0.70, P < 0.0001). Despite the
      observed overall shift from HO toward CO; no statistically significant difference
      in the HO-CDI event number and proportion was detected (28 [21.4%] vs. 22
      [29.1%], P = 0.094). Conclusion: Short-term BPAs use is associated with
      significant increase in the overall CDI incidence and prevalence along with a non
      statistically significant decline in HO-CDI proportion. Final analysis with full
      sample size is essential to provide a better picture about the long-term effect.

PMID- 30090748
TI  - Prevalence, diagnosis, and management of iron deficiency and iron deficiency
      anemia among Syrian children in a major outpatient center in Damascus, Syria.
AB  - Background: Given the public health significance of anemia, the long-term
      sequelae of iron deficiency anemia (IDA) on children, the expected effect of war
      on the trends of anemia in Syrian society, and the lack of assessment on the
      national burden of anemia and/or iron deficiency (ID) data, there is a vital need
      to investigate all-cause anemia, ID, and IDA in Syria during the crisis.
      Objective: To investigate the prevalence of ID and IDA in Syrian children, the
      effectiveness of oral iron supplements in the management of ID, and the
      diagnostic effectiveness of conventional iron markers. Methods: We conducted a
      retrospective study on hemoglobin (Hb) levels in 4-month-old to 14-year-old
      children and a prospective study on hematological (complete blood count,
      reticulocytes, and reticulocyte Hb content) and biochemical iron indices (serum
      ferritin, iron, and total iron-binding capacity) of infants visiting the primary
      care clinic at Children's Hospital in Damascus, Syria. Results: Of the 1128
      children in the retrospective study, 648 children (57%) were found to be anemic,
      with 417 (37%) moderately-severely anemic. The prevalence of ID and IDA in the
      135 children of the prospective study was 71.85% and 55.55%, respectively.
      Infants with ID who underwent a 4-8-week course of oral iron supplementation
      demonstrated good responsiveness. Except mean corpuscular hemoglobin (MCH),
      conventional iron markers (i.e., ferritin) routinely used to assess iron status
      proved unreliable. Conclusion: This study reveals a high prevalence of anemia,
      ID, and IDA among a group of apparently healthy Syrian children. Our findings
      necessitate a framework of urgent public health interventions that can address
      two major limitations; the poor follow-up by the parents and unreliability of the
      conventional iron diagnostic markers. MCH may represent a simple and cheap ID
      screening index in children.

PMID- 30090749
TI  - Knowledge, attitude, and practices associated with the diagnosis and management
      of skin and soft-tissue infections among medical students, residents, and
      attending physicians.
AB  - Skin and soft-tissue infections (SSTIs) are commonly encountered by medical
      students, residents, and trainees. The Infectious Diseases Society of America
      (IDSA) has updated its recommendations regarding SSTI diagnosis and management in
      June 2014. We assessed knowledge, attitude, and practices toward diagnosis and
      management of SSTIs using an online survey. We disseminated the survey to medical
      students, residents, and attending physicians practicing in family and internal
      medicine department at a university-based hospital. A total of 103 surveys were
      completed out of 121 sent (85.1%) between July 2015 and March 2016. There were
      nine medical questions in the survey. The mean of correct answers was 4.5/9 +/-
      2.0. Medical knowledge correlated with the level of education (P < 0.001) but not
      with subspecialty (P = 0.97). Around 35% were familiar with the updated IDSA
      guidelines pertaining to SSTIs. The majority (85%) responded that the hospital
      staff would benefit from additional training and 75% agreed that more antibiotic
      stewardship education is needed. Our study shows that there are significant
      opportunities for development among students and physicians who encounter SSTIs.

PMID- 30090750
TI  - Delayed bilateral obturator nerve injury due to compressing bilateral pelvic
      lymphoceles after robot-assisted laparoscopic radical prostatectomy and bilateral
      lymphadenectomy for prostatic carcinoma.
AB  - A clinically significant obturator nerve injury is uncommon after robot-assisted
      radical prostatectomy and lymphadenectomy. If the injury is due to a direct
      intraoperative event such as transection or stretching of the nerve, the patients
      present typically in the immediate postoperative period. On the other hand, an
      indirect injury through compression of the nerve through a pelvic fluid
      collection (hematoma or lymphocele) progresses insidiously and delays the
      presentation of these patients making a dilemma in recognizing these patients and
      differentiating them from those with other causes of neurological deficits. A
      delay in the correct management of the compressing collections may negatively
      affect the neurological function of the patient. We demonstrate a 61-year-old
      male who presented with pain and motor weakness of obturator origin 1 week after
      robot-assisted radical prostatectomy and lymphadenectomy for prostatic cancer.
      The computed tomography scan showed bilateral pelvic lymphoceles possibly
      compressing the obturator nerves. The neurological function has improved after
      evacuation of these collections. This case emphasizes the importance of
      considering delayed postsurgical compression of the obturator nerve in our
      differential diagnosis when patients present with typical signs and symptoms of
      obturator nerve injury after robot-assisted radical prostatectomy and
      lymphadenectomy. Early diagnosis and evacuation of these collections would
      improve the neurological outcome.

PMID- 30090751
TI  - Aggressive orbital rhabdomyosarcoma in adulthood: A case report in a public
      hospital in Damascus, Syria.
AB  - Orbital rhabdomyosarcoma (RMS) is a highly malignant tumor that originates mainly
      from mesenchymal tissue. It is considered a rare childhood malignancy; therefore,
      presentation in adulthood is scarce. In this case report, a 36-year-old male
      patient presented with a rapidly progressive RMS of the left orbit. The patient
      was treated in a different institution with radiochemotherapy with good response.
      However, relapse occurred after 2 months of completing the course, as rapid
      growing proptosis. Computed tomography scan revealed a lesion in the left orbit
      with invasion of the left ethmoid cells and the left maxillary sinus.
      Exenteration of the left orbit with the left partial maxillectomy and
      ethmoidectomy was performed. RMS is a highly aggressive malignancy that should be
      considered in any orbital mass that progresses rapidly. Surgery should be the
      first line in treatment. Delay in diagnosis and inappropriate treatment
      negatively affects the outcome.

PMID- 30090752
TI  - Human menopausal gonadotropin-induced bioprosthetic valve thrombosis.
AB  - Bioprosthetic valve thrombosis (BPVT) is a rare but potentially life-threatening
      complication. Human menopausal gonadotropin (hMG) is commonly used for ovulation
      induction and has been associated with arterial and venous thrombosis. We
      reported a case of BPVT related to in vitro fertilization in a 39-year-old
      female, who underwent redo mitral valve replacement. To the best of our
      knowledge, this is the first case of hMG-induced BPVT in a young female patient.

PMID- 30090753
TI  - Chiclero's ulcer: An unusual presentation of Leishmania tropica in Syria.
AB  - Cutaneous leishmaniasis (CL) has been an endemic disease in Syria for decades.
      The first reports of CL from the Syrian city Aleppo date back to the 17th
      century. The recent crisis has further empowered the spread of this infection not
      only in Syria, but also in the neighboring countries. Here, we describe a case of
      a 67-year-old patient with a 6-month, nonhealing ulcerative lesion of the left
      auricle. It was initially diagnosed as either a squamous or a basal cell
      carcinoma. However, the biopsy revealed an unexpected finding of Leishmania
      amastigotes in the histiocytes. Consequently, CL of the auricle, chiclero's
      ulcer, was diagnosed. Polymerase chain reaction, in turn, revealed Leishmania
      tropica to be the causing factor; a rather rare one for chiclero's ulcer. The
      lesion completely resolved after a 3-week glucantime regimen, without any
      recurrence after an 8-month follow-up.

PMID- 30090754
TI  - Promoting an academic culture in the Arab world.

PMID- 30090755
TI  - Hemispherotomy and Functional Hemispherectomy: Indications and Outcomes.
AB  - Hemispherectomy constitutes an established surgical method in the management of
      patients with medically intractable epilepsy secondary to severe unilateral
      hemisphere damage. As opposed to focal resections, in hemispherotomies, the
      entire hemisphere is disconnected from the remaining nervous system, including
      the functional regions and fibers. Despite this, hemispherotomy is recommended
      for certain indications, and has good functional and epilepsy outcomes. Here we
      describe the indications, epilepsy outcomes, and surgical techniques for several
      hemispheric surgeries.

PMID- 30090756
TI  - Surgical Treatment of Lesional Mesial Temporal Lobe Epilepsy.
AB  - Lesional mesial temporal lobe epilepsy (mTLE) concerns a lesion other than mesial
      hippocampal sclerosis present in the mesial temporal lobe and causing seizures.
      The lesions are usually composed of focal cortical dysplasia (FCD) or are
      tumorous. These are good candidates for surgical treatment. Sometimes, it is
      difficult to distinguish between tumors and FCD and to determine the extent of
      required removal. 11C-methionine positron emission tomography (PET) is helpful in
      differentiating lesions before surgery in lesional mTLE. In 11C-methionine PET
      imaging, tumors show a hot uptake, whereas FCD does not. In case of tumorous
      conditions, the removal of only specific lesions may be considered because the
      seizure outcome is dependent on complete excision of the tumor. There are several
      ways to safely access mesial temporal structures. The transsylvian-transcisternal
      approach is a good way to access the mesial structures while preserving the
      lateral and basal temporal structures. Actual lesions associated with
      epileptogenesis in FCD may be larger than they appear on magnetic resonance
      imaging. For this reason, evaluations to locate sufficient epileptogenic foci,
      including invasive studies, should be completed for FCD, and epilepsy surgery
      should be performed according to these results. Regardless, the ultimate goal of
      all epilepsy surgeries is to maximize seizure control while maintaining
      neurological function. Therefore, a tailored approach based on the properties of
      the lesion is needed.

PMID- 30090757
TI  - Technical Implications in Revision Surgery for Deep Brain Stimulation (DBS) of
      the Thalamus for Refractory Epilepsy.
AB  - Background and Purpose: Implantation of deep brain stimulation (DBS) electrodes
      in the anterior nucleus of the thalamus (ANT) or the centromedian nucleus (CM),
      for the treatment of refractory epilepsy, is technically demanding. To enhance
      the accuracy of electrode placement within the ANT and CM, we analyzed our
      experience with electrode revision surgery in ANT and CM DBS and investigated the
      cause of misplacement and verifying methods for accurate placement. Methods: A
      retrospective analysis of the medical records of 23 patients who underwent DBS
      for refractory epilepsy during the period from 2013 to 2016 was performed.
      Results: Misplacement of the electrode occurred in 1 (25%) of 4 ANT DBS and 2
      (14.3%) of 14 patients with CM DBS performed in our institute, and revision
      surgery was performed in three patients. During this period, we performed three
      revision surgeries for misplaced electrodes in ANT DBS that were performed at
      another hospital. Therefore, we performed six revision surgeries (four in ANT,
      two in CM) for mistargeted DBS electrodes for thalamic DBS. Transventricular lead
      placement and an anatomical targeting of the ANT was the cause of misplacement in
      the ANT and intraoperative brain shift was found to be the cause in the CM. For
      verification of the location of lead placement, magnetic resonance imaging (MRI)
      was superior to computed tomography and electroencephalography (EEG).
      Conclusions: To reduce the rate of electrode misplacement for refractory
      epilepsy, image-based targeting of the ANT according to individual anatomical
      variation, and efforts to minimize intraoperative brain shift are essential. To
      verify the location of the electrode, MRI examination is mandatory in DBS for
      refractory epilepsy.

PMID- 30090758
TI  - Use of the Modified Atkins Diet in Intractable Pediatric Epilepsy.
AB  - Background and Purpose: The modified Atkins diet is a less restrictive
      alternative to the ketogenic diet (KD), allowing unlimited protein, fat,
      calories, and fluid intake. Moreover, it can be started on an outpatient basis
      without requiring a fast. This study evaluated the efficacy, tolerability, and
      compliance of the modified Atkins diet in intractable pediatric epilepsy.
      Methods: We retrospectively reviewed the medical records of 26 pediatric patients
      (10 males and 16 females) with intractable epilepsy who were treated using the
      modified Atkins diet at Samsung Medical Center from January 2011 to March 2017.
      Results: The mean age at initiation of the modified Atkins diet was 10.9 (range,
      2-21) years. The diet was continued for a mean duration of 5.9 (range, 1-16)
      months. After 6 months, 10 (38.5%) remained on the diet, of whom six (60%) had >
      50% seizure reduction and two (20%) became seizure free. Four of 26 patients
      (15.4%) reported side effects of the diet, including constipation (n = 2) and
      lipid profile elevations (n = 2). Mean body mass index (BMI) was reduced from
      22.6 to 20.9 kg/m2 (p < 0.05) in 13 patients who continued the diet for >= 3
      months. Four of these patients (30.8%) were overweight (BMI > 25 kg/m2) before
      initiating the diet and were satisfied with their BMI changes from a mean of 30.3
      to 27 kg/m2 (p < 0.05). Food refusal (n = 3) and poor parental compliance (n = 3)
      were the common reasons cited for cessation. Conclusions: The modified Atkins
      diet may be an alternative treatment option for children with intractable
      epilepsy who are unable to tolerate KD because of food intake-related
      restrictiveness or adverse effects. The continuous support of healthcare
      professionals and families plays a key role in diet maintenance.

PMID- 30090759
TI  - Predictors of Seizure-Related Injuries in an Epilepsy Cohort from North India.
AB  - Background and Purpose: To identify predictors of seizure-related injury (SRI)
      and death in people with epilepsy (PWE) in a North Indian cohort. Methods: This
      ambispective cohort study included PWE registered in an epilepsy clinic in Delhi
      between May 2010 and December 2011. Five hundred twenty-six patients were
      enrolled and followed for 25 months. Patients were categorized into two groups
      based on SRI/no SRI during the study period. We analyzed various factors to
      identify predictors of SRI and death. Results: Of 526 patients, 355 (67.5%)
      reported having no SRIs and 171 (32.5%) had sustained an SRI. Among patients with
      SRI, 72.5% were male; 62% of those with no SRI were male. The injury type
      included soft tissue (60%), head trauma (20%), dental trauma (10%), orthopedic
      (10%), and burns (5%). On univariate analysis, factors predicting SRI occurrence
      were male gender, abnormal birth history (p < 0.01), abnormal mental status (p <
      0.01), seizure duration (p < 0.04), daytime seizures (p < 0.05), dependence on a
      caregiver (p < 0.008), and uncontrolled seizures (p < 0.001), history of cluster
      seizures or status epilepticus (p < 0.001), occurrence of generalized tonic
      clonic seizures (GTCS), and use of >3 antiepileptic drugs (p < 0.008). On
      multiple logistic regression analysis, male gender, uncontrolled seizures,
      history of cluster seizures or status epilepticus, and GTCS were significant risk
      factors. Sixteen deaths occurred in our cohort, and 13 fit the definition of
      probable sudden unexpected death in epilepsy (SUDEP). Most patients with SUDEP
      had an unwitnessed event (69.2%). The only significant factor in predicting death
      was uncontrolled seizures. Conclusions: Male gender, occurrence of GTCS,
      uncontrolled seizures, and history of cluster seizures or status epilepticus
      predicted SRI occurrence in PWE. Precautions should be taken by caregivers of
      patients with these risk factors, to prevent injury.

PMID- 30090760
TI  - Seizure-Related Cortical Volume Alterations in Alzheimer's Disease: A Preliminary
      Study.
AB  - Background and Purpose: Alzheimer's disease (AD) leads to cognitive dysfunction
      and neuronal loss, both of which can be exacerbated by seizures. For the
      treatment and diagnosis of AD, it is imperative to identify the cortical
      characteristics of comorbidities of AD such as seizures. The present study
      investigated the alterations in cortical volumes in patients with comorbid AD and
      seizures. Methods: In this retrospective study, magnetic resonance T1-weighted
      brain images were collected from six patients with early AD or amnestic mild
      cognitive impairment without seizures (AD-No Seizure, age: 66.17 +/- 4.92 years)
      and six individuals with seizures (AD-Seizure, age: 80.33 +/- 4.63 years). The
      gray matter volumes estimated from the T1 images were compared between the groups
      using nuisance variables (e.g., age). Subsequently, a correlation analysis was
      performed to investigate the relationship between cortical structure and global
      cognitive function. Results: AD-Seizure group showed volumetric alterations
      compared with AD-No Seizure group. In the volumetrically altered regions,
      correlation analysis revealed that the AD-Seizure group showed a positive
      correlation between the mini-mental state examination (MMSE) score and cortical
      volume, with smaller volumes than the AD-No Seizure group in the right
      parahippocampal gyrus, left angular gyrus, and middle temporal gyrus. The AD-No
      Seizure group showed negative correlations with MMSE score in the volume of right
      inferior frontal gyrus and cerebellar culmen and a positive correlation with the
      volume of the left middle frontal gyrus. Conclusions: Our findings revealed that
      smaller temporal region volumes are predictive of cognitive dysfunction in AD
      patients with seizures. Given that these temporal areas overlap with regions
      showing abnormal brain activities in AD patients with seizures, these results
      suggest synergistic effects of AD and seizures on cortical volume and cognitive
      function.

PMID- 30090761
TI  - Anti-NMDAR Encephalitis in a 13-Year-Old Female: A 24-Month Clinical Follow-Up.
AB  - Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a rare autoimmune
      disorder manifesting as seizures, movement disorders, and psychiatric changes.
      However, there have been few case reports concerning this disorder in South
      Korean children. The current case report describes a pediatric patient with anti
      NMDAR encephalitis. A 13-year-old female patient developed clonic movements of
      the right arm followed by aphasia, paresthesia, and right-sided hemiparesis. The
      electroencephalogram (EEG) results indicated electroclinical seizures arising
      from the left temporal area. Brain magnetic resonance imaging (MRI) revealed high
      signal intensity and cortical swelling in left temporal lobe. Anti-NMDAR
      antibodies were detected in the cerebrospinal fluid (CSF). The patient was
      treated with intravenous immunoglobulin and high-dose methylprednisolone and
      showed partial improvement in language skills, paresthesia, and motor power. The
      brain MRI and EEG results also indicated improvement. However, anti-NMDAR
      antibodies persisted in the CSF. After four doses of rituximab, the patient
      exhibited complete recovery of language and motor skills, and was seizure free
      under treatment with antiepileptic medication. There were no residual anti-NMDAR
      antibodies in the CSF at her 24-month follow-up visit. This case report
      elucidates the benefits of early intervention using rituximab to improve
      neurological deficits and achieve baseline recovery in patients with anti-NMDAR
      encephalitis.

PMID- 30090762
TI  - Tonic Upward Eyeball Deviation Mimicking Non-Convulsive Occipital Lobe Status
      Epilepticus That Was Induced by Hydrocephalus.
AB  - Several seizure-like symptoms are difficult to differentiate from epileptic
      convulsion, and then if they were misdiagnosed, they could be led to grave
      prognosis. A 41-year-old man was referred to the emergency room due to
      unconsciousness. Brain computed tomography (CT) revealed acute subdural
      hemorrhage along the left frontal lobe, and intraparenchymal hemorrhage in the
      left temporo-occipital lobe. After emergent decompressive craniectomy, he
      recovered an alert mental state but became progressively drowsy. Four days later,
      virtually continuous tonic upward eyeball deviation was observed. He had been
      taking antiepileptic drugs following an occipital lobectomy 20 years prior due to
      intractable epilepsy, and we assumed these upward eyeball deviations were
      symptoms of non-convulsive occipital lobe status epilepticus. Hence, doses and
      classes of antiepileptic drugs were modified, but clinical manifestations did not
      improve. Follow-up brain CT revealed newly developed hydrocephalus and
      compression of the mesencephalon. His symptoms fully resolved after a ventriculo
      peritoneal shunt operation. In this case report, we describe the case of a
      patient exhibiting tonic upward eyeball deviation induced by hydrocephalus that
      was not associated with a seizure.

PMID- 30090763
TI  - Rationale for Combining Bispecific T Cell Activating Antibodies With Checkpoint
      Blockade for Cancer Therapy.
AB  - T cells have been established as core effectors for cancer therapy; this has
      moved the focus of therapeutic endeavors to effectively enhance or restore T cell
      tumoricidal activity rather than directly target cancer cells. Both antibodies
      targeting the checkpoint inhibitory molecules programmed death receptor 1 (PD1),
      PD-ligand 1 (PD-L1) and cytotoxic lymphocyte activated antigen 4 (CTLA4), as well
      as bispecific antibodies targeting CD3 and CD19 are now part of the standard of
      care. In particular, antibodies to checkpoint molecules have gained broad
      approval in a number of solid tumor indications, such as melanoma or non-small
      cell lung cancer based on their unparalleled efficacy. In contrast, the efficacy
      of bispecific antibody-derivatives is much more limited and evidence is emerging
      that their activity is regulated through diverse checkpoint molecules. In either
      case, both types of compounds have their limitations and most patients will not
      benefit from them in the long run. A major aspect under investigation is the lack
      of baseline antigen-specific T cells in certain patient groups, which is thought
      to render responses to checkpoint inhibition less likely. On the other hand,
      bispecific antibodies are also restricted by induced T cell anergy. Based on
      these considerations, combination of bispecific antibody mediated on-target T
      cell activation and reversal of anergy bears high promise. Here, we will review
      current evidence for such combinatorial approaches, as well as ongoing clinical
      investigations in this area. We will also discuss potential evidence-driven
      future avenues for testing.

PMID- 30090764
TI  - Nipah virus epidemic in southern India and emphasizing "One Health" approach to
      ensure global health security.
AB  - Nipah virus (NiV) encephalitis first reported in "Sungai Nipah" in Malaysia in
      1999 has emerged as a global public health threat in the Southeast Asia region.
      From 1998 to 2018, more than 630 cases of NiV human infections were reported. NiV
      is transmitted by zoonotic (from bats to humans, or from bats to pigs, and then
      to humans) as well as human-to-human routes. Deforestation and urbanization of
      some areas have contributed to greater overlap between human and bat habitats
      resulting in NiV outbreaks. Common symptoms of NiV infection in humans are
      similar to that of influenza such as fever and muscle pain and in some cases, the
      inflammation of the brain occurs leading to encephalitis. The recent epidemic in
      May 2018 in Kerala for the first time has killed over 17 people in 7 days with
      high case fatality and highlighted the importance of One Health approach. The
      diagnosis is often not suspected at the time of presentation and creates
      challenges in outbreak detection, timely control measures, and outbreak response
      activities. Currently, there are no drugs or vaccines specific for NiV infection
      although this is a priority disease on the World Health Organization's agenda.
      Antivirals (Ribavirin, HR2-based fusion inhibitor), biologicals (convalescent
      plasma, monoclonal antibodies), immunomodulators, and intensive supportive care
      are the mainstay to treat severe respiratory and neurologic complications. There
      is a great need for strengthening animal health surveillance system, using a One
      Health approach, to detect new cases and provide early warning for veterinary and
      human public health authorities.

PMID- 30090766
TI  - Doctor in default?

PMID- 30090765
TI  - Strengths and limitations of a family physician.
AB  - Family physicians (FP) practising in different parts of the world may require
      different sets of knowledge and skills to satisfy the needs of the communities in
      which they work as well as the requirements of the professional bodies with which
      they are registered. This article gives an overview of the strengths and
      limitations of the FP globally and more specifically within India, South Africa,
      and the United States of America. The historical context and evolution of FM as a
      clinical and academic discipline is discussed in this article. The article
      recommends suggestions for a better future for Family Medicine as a specialty
      thereby providing quality primary healthcare to the community, based on the needs
      of the population of each country.

PMID- 30090768
TI  - Principles of family medicine practice: Lessons gleaned over a lifetime in
      practice.
AB  - The term "principles" refers to a set of defining attributes and values that lie
      at the heart of a discipline. These are largely discovered by reflection and
      practice rather than learned by formal instruction. This article is written as a
      reflective dialogue between two teachers of family medicine, one who has been
      practicing for nearly five decades and another with training in contemporary
      academic family medicine, using a selection of case stories drawn from the
      practice of the first author. Several principles of family medicine such as
      "broad-based specialty"; "person and family orientation"; "continuity of care";
      "community based care"; "building a trusting relationship"; "counseling"; and "an
      effective steward of resources" are highlighted. It is hoped that the above
      discussion will enable students and practitioners of family medicine to be more
      effective in delivering primary care and appreciate the privilege they have of
      serving as family physicians in the community.

PMID- 30090767
TI  - Joint position statement Indian Association of Palliative Care and Academy of
      Family Physicians of India - The way forward for developing community-based
      palliative care program throughout India: Policy, education, and service delivery
      considerations.
AB  - Purpose: This joint position statement, by the Indian Association of Palliative
      Care (IAPC) and Academy of Family Physicians of India (AFPI), proposes to address
      gaps in palliative care provision in the country by developing a community-based
      palliative care model that will empower primary care physicians to provide basic
      palliative care. Evidence: India ranks very poorly, 67th of 80 countries in the
      quality of death index. Two-thirds of patients who die need palliative care and
      many such patients spend the last hours of life in the Intensive care unit. The
      Indian National Health Policy (NHP) 2017 and other international bodies endorse
      palliative care as an essential health-care service component. NHP 2017 also
      recommends development of distance and continuing education options for general
      practitioners to upgrade their skills to provide timely interventions and avoid
      unnecessary referrals. Methods: A taskforce was formed with Indian and
      International expertise in palliative care and family medicine to develop this
      paper including an open conference at the IAPC conference 2017, agreement of a
      formal liaison between IAPC and AFPI and wide consultation leading to the
      development of this position paper aimed at supporting integration, networking,
      and joint working between palliative care specialists and generalists. The WHO
      model of taking a public health approach to palliative care was used as a
      framework for potential developments; policy support, education and training,
      service development, and availability of appropriate medicines. Recommendations:
      This taskforce recommends the following (1) Palliative care should be integrated
      into all levels of care including primary care with clear referral pathways,
      networking between palliative care specialist centers and family medicine
      physicians and generalists in community settings, to support education and
      clinical services. (2) Implement the recommendations of NHP 2017 to develop
      services and training programs for upskilling of primary care doctors in public
      and private sector. (3) Include palliative care as a mandatory component in the
      undergraduate (MBBS) and postgraduate curriculum of family physicians. (4)
      Improve access to necessary medications in urban and rural areas. (5) Provide
      relevant in-service training and support for palliative care to all levels of
      service providers including primary care and community staff. (6) Generate public
      awareness about palliative care and empower the community to identify those with
      chronic disease and provide support for those choosing to die at home.

PMID- 30090769
TI  - Iatrogenesis: A review on nature, extent, and distribution of healthcare hazards.
AB  - Modern medicine is given overarching importance to tackle disease in the human
      body than environmental determinants. Although, most of the literature confirms
      that the determinants of disease are there in the environment. Yet in the modern
      times what is being emphasized is highly limited and reductionist approach of
      curing ailments in the human body only, which is one of the desired interventions
      but is full of other side effects and risks leading to iatrogenic reactions. Most
      of the literature establishes that modern medicine is one of the major threats to
      the world health. Besides treating disease at the clinical level, rational, and
      well-thoughtout changes in the overall environment can positively impact the
      nature, extent, and distribution of disease.

PMID- 30090770
TI  - Evaluation of red flags minimizes missing serious diseases in primary care.
AB  - Primary care physicians encounter a broad range of problems and therefore require
      a broad knowledge to manage patients. They encounter patients at early
      undifferentiated stage of a disease and most of the presentations are due to non
      sinister problems but in minority of patients same presentations could be due to
      serious conditions. One of the main tasks of a primary care doctor is to
      marginalize the risk of missing these serious illnesses. To achieve this they can
      look for red flags which are clinical indicators of possible serious underlying
      condition. Red flags are signs and symptoms found in the patient's history and
      clinical examination. Evaluation of red flags is of paramount important as
      decision making is mainly dependent on history and examination with the
      availability of minimal investigatory facilities at primary care level. Some Red
      flags like loss of weight and loss of appetite are general in nature and could be
      due to many pathologies while hematemesis and melena are specific red flags which
      indicate GIT bleeding. All red flags, whether highly diagnostic or not, general
      or specific, warn us the possibility of life-threatening disorders. The term 'red
      flag' was originally associated with back pain and now lists of red flags are
      available for other common presentations such as headache, red eye and dyspepsia
      as well. Identification of red flags warrant investigations and or referral and
      is an integral part of primary care and of immense value to primary care doctors.

PMID- 30090771
TI  - Evolution of the Dubai health authority's residency training program: A 25-year
      review, challenges and outcomes.
AB  - Background: The Dubai Residency Training Program (DRTP) is a structured
      postgraduate educational training program started on 1992 to improve healthcare
      in the United Arab Emirates (UAE) through education and training; align doctors'
      training in the UAE with internationally recognized standards; deliver
      educational best practice; and achieve a balance between clinical service
      delivery and continuing professional development. The aim of this paper is to
      review the experiences, challenges and outcomes of the DRTP over the last 25
      years. Methods: All documentation relating to the DRTP was reviewed and
      reevaluated. Results: The DRTP has become a very solid foundation; yet, one of
      the major challenges we are facing is containing the balance between the health
      service and education. Another challenge is that our capacity for training is
      limited, in spite of demand, we are not yet able to open all specialties needed
      in the UAE. Finally, there is a mandate to separate the educational body from
      service to better govern the education. Conclusions: The time has come, however,
      for the UAE to have its own medical specialty board. This would further support
      high quality, comprehensive specialty training to deliver the bespoke workforce
      required by the Dubai Health Authority. The concept of structured training where
      the resident knows what, when, and how to learn the required knowledge and skills
      is already established, and the UAE has the required numbers of highly trained
      professionals to form the board. Nevertheless, we should neither be complacent
      nor underestimate the challenges that remain to deliver the UAE specialty board.

PMID- 30090772
TI  - Vitamin D deficiency in India.
AB  - Vitamin D is a fat-soluble vitamin playing a vital role in human physiology.
      Vitamin D deficiency is prevalent worldwide. This deficiency has many
      consequences which are still being explored, apart from the well-known skeletal
      complications. With this review, we aim to summarize the existing literature on
      Vitamin D status in India and understand the enormity of the problem. The
      prevalence of Vitamin D deficiency ranged from 40% to 99%, with most of the
      studies reporting a prevalence of 80%-90%. It was prevalent in all the age groups
      and high-risk groups alike. With the consequences of Vitamin D deficiency,
      namely, autoimmune diseases, cardiovascular diseases, cancer, and tuberculosis
      being explored, we can imagine the burden it would cause in our country. We need
      to create awareness among the public and healthcare providers about the
      importance of Vitamin D and the consequences of deficiency. Our Indian diet
      generally fails to satisfy the daily requirement of Vitamin D for a normal adult.
      This stresses on the need for fortifying various food with Vitamin D, through the
      national programs. This silent epidemic should be addressed appropriately with
      concrete public health action.

PMID- 30090773
TI  - Primary school female teachers' knowledge, attitude, and practice toward students
      with epilepsy in Riyadh, Saudi Arabia.
AB  - Background: Epilepsy is the most neurological condition prevalent in humanity and
      it is associated with stigma and discrimination. Knowledge and practice of
      primary care teachers toward students with epilepsy, especially at young age, is
      imperative for their development. Objectives: This study was designed to assess
      the level of knowledge, attitude, and practice of female primary school teachers
      toward students with epilepsy in Riyadh, Saudi Arabia. Subjects and Methods: In
      this cross-sectional study, 582 female primary school teachers had volunteered.
      They were assessed on their knowledge, attitude, and practice toward students
      with epilepsy using a self-administrated questionnaire. The questionnaire was
      cross-culturally validated before the distribution. Results: The results suggest
      above-average familiarity with epilepsy (79.2%). Younger teachers are less likely
      to associate epilepsy with retardation (P = 0.038). In general, the attitude was
      positive among the teachers, and 36.9% felt that the students should be treated
      normally and 63.1% with compassion toward them. Only 14.3% answered that
      epileptic students should be transferred to special need schools. Highly educated
      teachers were less likely to feel that epileptic students can cause problems (P =
      0.038). The practice was poor with 31.8% expressed the ability to provide first
      aid to epileptic students. Only 27.5% accepted to give the students prescribed
      medications. Conclusion: The knowledge about epilepsy needs improvement among
      primary school teachers in Riyadh. Public level interventions through proper
      courses can provide a leverage. The higher level of knowledge can be pivotal in
      increasing the positive attitude and practice of teachers toward epileptic
      students.

PMID- 30090774
TI  - Musculoskeletal problems in frequent computer and internet users.
AB  - Aim: This study was carried out to see the frequency of musculoskeletal problems
      in frequent Computer and Internet Users. Methods: This was a Cross Sectional
      Study performed in the community and we chose Office workers and students aged 18
      to 50 years using Computers and Internet for not less than 3 hours per day. After
      a verbal consent, they were given a questionnaire in English. People having prior
      diagnosed musculoskeletal problems were excluded. Results: Total number of
      participants were 150, out of which 80% were males, and 67 (44.7%) suffered from
      musculoskeletal problems, affecting at least one of the four anatomical sites
      (low back, neck, shoulder, wrist/hand). Common symptoms were Headache, which was
      seen in 46% and neck pain in 41.3% of subjects. Whereas wrist pain was least
      commonly seen in 16% of subjects. Independent t test was used to compare the
      musculoskeletal problems with duration of computer use which has a significant
      value i.e. less than 0.05. Conclusion: Musculoskeletal symptoms are quite common,
      headache and back pain being most common symptoms. These symptoms are associated
      with prolonged use of computer and internet and often left unreported and
      unrelated.

PMID- 30090775
TI  - Determinants of appropriate knowledge on human immunodeficiency virus
      postexposure prophylaxis among professional health-care workers in Sokoto,
      Nigeria.
AB  - Introduction: The prevention of human immunodeficiency virus (HIV/AIDS) among
      health-care workers (HCWs) has remained a major topical issue worldwide.
      Accidental transmission of HIV infection to HCWs during occupational exposure is
      a real threat today. The study aimed to assess the knowledge, attitude, and
      practice of postexposure prophylaxis (PEP) among HCWs in a tertiary health
      institution in Sokoto, Northwestern Nigeria. Methodology: The study was carried
      out at Usmanu Danfodiyo University Teaching Hospital, Sokoto, through a cross
      sectional descriptive study design; a total of 156 participants were recruited
      using a stratified sampling technique. Data were collected using a semi
      structured, self-administered questionnaire and analyzed using SPSS computer
      software after obtaining ethical clearance from the Health Ethics and Research
      Committee of the teaching hospital. Results: A total of 87.2% (136) of the
      respondents had heard of PEP and 71.8% (112) thought that HIV/AIDs could be
      prevented through PEP. A total of 71.2% (111) had good knowledge about PEP,
      whereas 86.8% (118) had a positive attitude toward PEP. Conclusion: Although the
      study demonstrated high knowledge and positive attitude toward PEP, the
      observance of safety measures against needlestick injuries that could result in
      HIV infections was abysmally low. There is the need to create more awareness and
      strengthen the use of PEP protocol by all cadres of health workers as this will
      go a long way in minimizing blood-borne infections.

PMID- 30090776
TI  - Biopsychosocial etiology of premenstrual syndrome: A narrative review.
AB  - Introduction: Premenstrual syndrome (PMS) is one of the most prevalent disorders
      at reproductive age and has a negative impact on emotions and performance of
      women. Since various factors play a role in the development of this syndrome, the
      present study was aimed to examine biopsychosocial etiology of PMS in the form of
      a narrative review. Materials and Methods: Relevant studies were collected based
      on the three subjects of biological, psychological, and social etiologies during
      1987-2015. First, Medical Subject Headings was used to specify the relevant
      keywords such as biological, psychological, social, and premenstrual syndrome
      which were used to search Internet databases including Google Scholar, Scopus,
      PubMed, PMDR, Ovid, Magiran, and Iranmedex, which led to collection of 1 book and
      26 Persian and English articles. Results: The results were classified into three
      sections. In the biological section, the effect and role of sex hormones and
      their changes in PMS were examined. In the psychological section, hypotheses on
      PMS and the role of psychological problems in the development of PMS were
      examined. In the social section, the role and social, religious, and cultural
      position of women and its relationship with PMS were examined. Conclusion: To
      reduce negative experiences of PMS, it is recommended that girls should be
      provided with necessary scientific information on puberty and premenstrual
      health. The results showed that paying attention to the complaint on premenstrual
      symptoms is significant in women's comprehensive assessment, and it plays an
      essential role in diagnosing psychological and physical annoying diseases.

PMID- 30090777
TI  - Is there a misuse of computed tomography in the diagnostic workup of headache? A
      retrospective record-based study in secondary health-care facility in Saudi
      Arabia.
AB  - Introduction: Headache disorders are one of the most prevalent global public
      health problems that require placing high demand on health-care Services. Since
      it is one of the most frequent complaints in clinical practice worldwide, it
      causes a considerable burden in terms of the social cost. The study aimed to give
      a guide for the decision on the utilization of computed tomography (CT) in the
      diagnostic workup and identify if patients require neurological imaging (CT) for
      proper diagnosis or not. Materials and Methods: The study was carried out in the
      Radiology Department in King Khalid Hospital, Al Kharj, Saudi Arabia from October
      15, 2016, to February 15, 2017. A retrospective record-based study conducted
      using the documented CT reports in the files of patients whom were referred to
      the radiology department complaining of any type of a headache. Results: The data
      included 210 patients 51% were males and 49% were females. The patients were
      distributed into age groups; the mean age was 38.46 standard deviation +/- 13.56.
      Among Saudi population, the etiology of headache was varying; the most prevalent
      type of headache was tension headache 25.71% of the total headache patients
      followed by cluster 25.24% and the migraine with the lowest proportionality. The
      majority of the patients' headache pain was mild 60%. Moreover, the CT reports
      for most of the patients were normal. Spearman Correlation test was used to see
      if there is a significance in using the CT for any patient who comes with
      symptoms including headache, and the results have shown that there is no
      association and clinical significance in using the CT for patients with headache
      without suspecting other clinical condition (P = 0.177). Conclusion: Headache
      disorders must be on the public-health agenda. Tension, migraine, and cluster
      type headaches represent the majority of primary headaches. Statistically no
      significance or need to obtain CT if there are no life-threatening conditions
      expected or trauma presented.

PMID- 30090778
TI  - Carotid intima-media thickness, flow-mediated dilatation and proteinuria in
      patients of human immunodeficiency virus-positive patients: A case-control study.
AB  - Introduction: Endothelium-dysfunction (ED) is a surrogate marker of coronary
      atherosclerotic disease. Carotid intima-media thickness (CIMT), flow-mediated
      dilatation (FMD), and proteinuria are surrogate markers of ED. Few studies have
      shown that patients with HIV have impaired endothelial function and are thus at
      risk of accelerated atherosclerosis. Materials and Methods: The present study
      assessed ED in HIV patients by various biophysical parameters as brachial artery
      FMD, CIMT, and proteinuria. A total of 43 HIV-infected patients were compared
      with 25 healthy controls who were healthy. Results: Mean age of patients with HIV
      was 33.84 +/- 5.61 years while that of healthy controls was 31.48 +/- 5.40 years.
      Male to female ratio among cases was 24:19 while among controls was 17:8. Mean
      CIMT was significantly higher among cases than control (0.513 +/- 0.079, 0.452 +/
      0.050 mm, respectively, P = 0.001). Percentage change in FMD was significantly
      lower among cases than control (3.27 +/- 2.01, 6.96 +/- 1.28, respectively, P =
      0.001). Urine protein grading was significantly different between cases and
      controls (P = 0.007), with stable HIV cases having significantly higher urine
      protein grading compared to healthy controls. However, no correlation was seen
      between CIMT, FMD, and proteinuria overall among cases and controls. Conclusions:
      HIV-infected patients have significant impairment of endothelial function, in the
      form of increased CIMT, impaired FMD, and more proteinuria as compared to healthy
      controls.

PMID- 30090779
TI  - The relationship between job motivation and its dimensions with organizational
      commitment and its dimensions in midwives of sanitary and therapeutic centers,
      Arak University of Medical Sciences, 2017.
AB  - Introduction and Aim: Human resources with the quality of desirable performance
      are the most important assets of the organization and increase the probability of
      success, survival, and progress of the organization. Midwives have a critical
      role in promoting the health of mothers and infants and survey the relationship
      between job motivation and organizational commitment can help health system
      managers and planners to improve the quality of the services provided. Methods:
      This is a cross-sectional and correlational study; samples of midwives in Arak
      University of Medical Sciences were selected by stratified sampling with
      proportional allocation method. The instrument of gathering was demographic
      information questionnaire, Herzberg's job motivation, and organizational
      commitment of Allen and Meyer. Data were analyzed by SPSS 16 software and (P <
      0.05) were considered significant. Results: There was a significant relationship
      between job motivation and organizational commitment and their dimensions (r =
      0.68, P < 0.001). The highest correlation between job motivation and emotional
      commitment (r = 0.77), normative commitment (r = 0.62), and continuous commitment
      (r = 0.55). The most related emotional commitment by way of communication (r =
      0.74), continuous commitment to salary and wages (r = 0.54), and normative
      commitment with the nature of midwifery was r = 0.61. Conclusion: The results
      show the importance of communication dimensions, salaries, and wages and the
      nature of job in the commitment of midwives in Markazi Province. More attention
      from health system administrators to these dimensions can be useful in increasing
      the motivation and organizational commitment of midwives in this province.

PMID- 30090780
TI  - Comparative morbidity profile of patients attending an Ayurveda clinic and a
      modern medicine clinic of a primary health center in rural Haryana, India.
AB  - Context: There is a paucity of data on the profile of patients accessing
      traditional systems of medicine. A comparison of profile of patients attending an
      Ayurveda clinic with that of modern medicine clinic will help in better
      understanding of utilization of services and preference for system of medicine by
      the patients seeking health care. Aim: The aim was to study the morbidity profile
      of patients who attended the Ayurveda clinic of a primary health center (PHC) in
      rural Haryana over 1 year and compared it with that of the modern medicine clinic
      attendees at the same facility. Materials and Methods: The study site was PHC,
      Dayalpur in block Ballabgarh, district Faridabad, Haryana, India. All new
      patients who attended the Ayurveda clinic of PHC Dayalpur in the year 2012 were
      included in the study. New attendees of modern medicine clinic of the same PHC in
      the year 2012 were used for comparison of profile of patients. Results: In year
      2012, of the total new patients registered at PHC, 26% attended Ayurveda clinic.
      The male-to-female ratio (0.8:1) was similar in both clinics. The representation
      of children up to 5 years and elderly was significantly higher (12.0% vs. 6.7%
      and 19.5% vs. 11.0%) in modern medicine clinic as compared to Ayurveda clinic.
      The most common morbidities seen in Ayurveda clinic were twak vikar or skin
      disease (12.3%), sandhivata or osteoarthritis (10.3%), and kasa or cough (8.5%).
      Three most common morbidities in modern medicine clinic were acute respiratory
      infection (35.7%), hypertension (10.6%), and acute febrile illness (9.2%).
      Conclusions: The study provided evidence that Ayurveda was popular among rural
      population in North India. Therefore, the Government of India's initiative of
      setting up Ayurveda clinic in PHCs is well founded.

PMID- 30090781
TI  - Knowledge and practice of first aid among parents attending Primary Health Care
      Centers in Madinah City, Saudi Arabia, A Cross Sectional Study.
AB  - Background: Rapid and right intervention of parents can limit disability and
      increase the chances of survival of the injured child and make a big difference
      in the outcome. Objectives: The objective of this study is to assess the
      knowledge and practice of first aid among parents attending PHCs in Al-Madinah
      city, 2017. Methods: A cross-sectional study was conducted in governmental
      primary healthcare centers in Al-Madinah Al-Munawwarah city (Saudi Arabia) during
      the year 2017. A representative sample of Saudi parents who live in Madinah and
      came to family medicine clinic in PHC was included. A pre-validated and self
      administered questionnaire was used for data collection. Results: The study
      included 390 parents. More than half of them (55.6%) were males. The age of 40%
      of them ranged between 31 and 40 years whereas that of 31.5% ranged between 20
      and 30 years. Majority of the parents (97.2%) were aware of first aid. The most
      commonly reported source of information about first aid was mass media (59%).
      Majority of the parents (93.3%) believe there must be training in first aid, and
      only 34.6% of them claimed that they attended a training course in first aid. The
      highest average knowledge percentage was observed regarding the first aid of
      diabetes mellitus (68.8%), followed by epilepsy (49.7%), incidents (37.5%) and
      finally injuries/fractures (36.7%). Higher educated parents, those with a
      moderate number of children (4-6), those reported nurses as the main source of
      information, those previously attended training in first aid, and those who had
      experience with incidents among their children expressed higher significantly
      first aid knowledge compared to their counterparts. Conclusions: First aid of
      various illnesses among parents in Al-Madinah city is not satisfactory,
      particularly regarding incidents, injuries, and fractures. However, the majority
      of them were willing to attend training courses in first aid at primary
      healthcare centers.

PMID- 30090782
TI  - Social anxiety and its effect on self-efficacy among family medicine residents in
      Riyadh.
AB  - Background: Social anxiety is a common disorder that characterized by fear of
      social situations. Social anxiety disorder causes several problems including
      alcohol abuse. Its prevalence is high, and it affects work and education. Self
      efficacy influences any action the individual takes. Aim: The aim of this study
      is to evaluate the prevalence of social anxiety disorder and its effect on self
      efficacy on family medicine residents. Materials and Methods: This study included
      200 participants of family medicine residents; two validated scales were
      incorporated in one questionnaire to investigate the social anxiety and self
      efficacy. Results: The prevalence rate of social anxiety was low among family
      medicine residents, and there was no difference between the levels of anxiety and
      other demographics, there was a negative correlation between social anxiety
      levels and self-efficacy. Conclusion: There was a negative correlation between
      social anxiety and self-efficacy, where high levels of social anxiety were
      related to low levels of self-efficacy.

PMID- 30090783
TI  - Development of a quality scoring tool to assess quality of discharge summaries.
AB  - Introduction: Timely, precise, and relevant communication between hospital-based
      clinicians and primary care physicians post-discharge (DC) ensures quality
      transitions, thereby reducing patient safety incidents and preventing
      readmission. At the present time there is limited knowledge of elements of
      quality or methods to score the quality criteria in the context of DC summaries.
      The Nova Scotia Health Authority, a provincial health system responsible for the
      delivery of services in a small Canadian province, embarked on a system-level
      approach to the standardization of DC summaries in an effort to improve quality
      and safety at care transitions from hospital to primary care. Materials and
      Methods: A comprehensive literature review to retrieve items relevant to quality
      in DC summaries, retrospective audit of charts, a consensus development process,
      and, finally, validation of a scoring tool were conducted in order to develop a
      quality scoring tool for DC summaries. Results: Relevant items were identified
      through the literature review and consensus development process. Corresponding
      definitions that were established assisted the development of the quality
      criteria, which were subsequently used to score the quality of DC summaries in
      our organization. Conclusion: The scoring tool developed through this work will
      be applied to help us gain a more in-depth understanding of quality in DC
      summaries and support the development of suitable education and quality processes
      in the health authority that can best support safe care transitions for patients.

PMID- 30090784
TI  - Evaluation of out-patient prescriptions in rural part of central Gujarat.
AB  - Background: The prescription error is a failure in the prescription writing
      process leading to wrong instructions about the identity of the recipient, the
      identity of the drug, the formulation, dose, route, timing, frequency, and
      duration of administration. This study is an effort directed to find errors in
      prescription writing and interventions to improve on such error-prone practices
      of prescription writing. Methods: This was a cross-sectional, observational study
      conducted to analyze the prescription writing errors in the outpatient department
      in the rural area of Anand district of Central Gujarat. Prescriptions were
      collected from two nearby rural areas of Anand city-Petlad and Anklav. The
      prescription copies so-obtained were analyzed as per the WHO guidelines for
      "Prescription Writing Errors." Results: Overall, 191 prescriptions were collected
      from both rural areas in the study. The highest number of prescriptions was
      collected from general practitioners, followed by surgeons and gynecologists.
      Name, qualification, and address of prescribers were mentioned in all the
      prescriptions while registration number was mentioned only in 14.10% of
      prescriptions. The esoteric symbol was mentioned in 63% of prescriptions.
      Prescribers signed their prescription only in 48% of prescriptions. A total of
      420 drugs were prescribed to the patients in the study. All but one drug were
      prescribed by brand name. Dosage form and route of administration of drugs were
      mentioned in >60% of drugs. Conclusion: Most medical schools provide some
      training in prescribing to medical undergraduates; however, this training is
      perceived to be suboptimal by medical students and junior doctors. Such training
      programs are the need of the hour.

PMID- 30090785
TI  - Investigation of factors affecting the tendency to choose the type of delivery in
      pregnant women referring to hospitals of Ardabil Province in 2016.
AB  - Background and Purpose: Childbirth is one of the most challenging events in a
      married woman's life and it has important emotional consequences for each woman.
      It is also a multidimensional process that has physical, physiological,
      psychological, emotional, cultural, and social dimensions. The aim of this study
      was to investigate the factors affecting the tendency to choose the type of
      delivery in pregnant mothers in hospitals of Ardabil Province in 2016.
      Methodology: This study is a cross-sectional research that was conducted on 300
      pregnant women who were referred to the hospitals for delivery during 3 months in
      2016. Data collection tools was a five-part questionnaire including demographic,
      awareness, attitude, abstract norm questionnaires (other's role) in choosing
      delivery method, and Behavioral Intention Questionnaire was used in choosing the
      type of delivery. Results: Statistically, there was not any significant
      relationship between level of awareness and type of delivery in pregnant mothers
      (P = 0.07). The mean scores of attitude in mothers with a tendency to natural
      delivery were 35.75 +/- 14.43, and in mothers with a tendency to cesarean was
      46.3 +/- 10.96. ANOVA test showed statistically a significant relationship
      between attitude toward cesarean and type of delivery (P < 0.05). Chi-square test
      showed statistically a meaningful relationship between the recommendations of
      acquaintances, mothers, husbands, and doctors with choosing a type of delivery (P
      < 0.05). Conclusion: Regarding the results of research, especially the positive
      attitude and high level of awareness in the choice of natural delivery, the
      promotion of natural delivery will be possible with education.

PMID- 30090786
TI  - A pilot study to determine the occurrence of concomitant diseases and drug intake
      in patients on antituberculosis therapy.
AB  - Introduction: Altered pharmacokinetics of antituberculosis (anti-TB) drugs due to
      interaction with non-TB medications or concomitant diseases may lead to
      suboptimal plasma levels of the affected drugs and hence contribute to the
      emergence of drug resistance in mycobacteria. Yet, few studies have investigated
      the prevalence of concomitant drug intake or concurrent diseases in patients on
      anti-TB therapy (ATT). The objective of this study is to study the prevalence of
      concomitant diseases and intake of non-TB drugs in patients on ATT. Methods:
      Adult patients who were undergoing treatment for TB at a directly observed
      treatment short-course (DOTS) center were interviewed to find out any concomitant
      drug intake and ailments they were suffering from. Data were also collected from
      the patients' treatment cards. Results: A total of 105 patients were interviewed
      for the study over a period of 1 month. Among these, 66 (62.9%) patients reported
      having taken a non-ATT drug in the last 3 months, 61 (58.1%) of which were drugs
      that may affect the ATT. A comparable number of patients (61 [58.1%]) reported
      suffering from one or the other concurrent illnesses or symptoms while on DOTS,
      including one patient with AIDS and eight with diabetes mellitus.
      Fluoroquinolones had been prescribed to four patients while on DOTS. Conclusion:
      A large proportion of the patients with TB were found to be on non-TB concomitant
      medications including drugs with potential for interactions that are capable of
      affecting ATT outcomes. It is, therefore, important that the patients and
      prescribing physicians be aware of any possible drug interactions.

PMID- 30090787
TI  - Emotional intelligence and anxiety, stress, and depression in Iranian resident
      physicians.
AB  - Background: Residency is one of the most critical periods of medical education.
      Residents are susceptible in high risk for mental problems which can affect the
      doctor-patient relationship. Emotional intelligence (EI) correlates closely with
      stress and mental health. Considering the important role of EI in medical
      education and with regard to lack of studies in this group in Iran, this study
      conducted to determine the relationship between EI and stress, anxiety, and
      depression in a sample of resident physician in our university of medical
      sciences. Materials and Methods: In this cross-sectional study, 245 residents
      were invited, but only100 questionnaires were analyzed, and the response rate was
      41%. From this, 26 were men and 74 were women. Bar-on EI questionnaire,
      Depression Anxiety Stress Scales-21, for evaluating the stress, anxiety, and
      depression and demographic characteristics were used. Results: The mean score of
      EI in resident physician was 330.24 +/- 38.5. The mean score of stress, anxiety,
      and depression was 17.8 +/- 8.6, 10.04 +/- 7.99, and 10.49 +/- 8.67 respectively.
      There was a negative relation between mean score of anxiety (R = -0.0525), stress
      (R = -0.639), and depression (R = -0.644) with a mean score of EI. Conclusion:
      Higher EI appears to be good predictors of lower stress, anxiety, and depression
      in resident physician.

PMID- 30090788
TI  - Evolution of family medicine residency training program in Dubai Health
      Authority: A 24-year review, challenges, and outcomes.
AB  - Introduction: It is well known that family medicine (FM) is a cornerstone for
      developing a community-based health-care system, and training family physicians
      is critical for the society. In Middle East, only 5%-10% of physicians, nurses,
      and health technicians are citizens. This demands more efforts toward having
      national FM practitioners in the country. The development of FM residency
      training program through the past two decades in Dubai has played a crucial rule
      in this aspect. Methods: The primary purpose of this study is to review the
      status of FM specialty training in the Emirates of Dubai throughout the past two
      decades. Results: The FM residency training program started since 1993 and had
      intake of 230 residents till 2017; out of which, 200 (87%) were female and 211
      (92%) were the United Arab Emirates national. From 176 residents who are supposed
      to be graduated by 2017, 162 (92%) completed 4-year training, 132 (75%) has got
      the Arab Board certificate, and 116 (66%) qualified by the Membership of the
      Royal College of General Practitioners (MRCGP) international. Conclusion: The
      present study revealed that despite all challenges, the well-structured FM
      program enabled the graduates to reach high clinical, administrative, leadership,
      and academic positions such as consultant (40), chief executive officer (1),
      chief advisor for primary care (1), director (9), head of sections (9),
      head/deputy head of primary health center (55), head of academic affair center
      (1), chair of MRCGP international (1), program director of FM (4), MRCGP convener
      (6), MRCGP coordinator (6), and MRCGP examiner (42). However, the program is
      still lacking certification by an international accreditation body. This will
      help in reaching a better balance between education and clinical duties for all
      trainers and faculty; and will positively advocate support for an environment
      conducive to learning for residents as well as faculty members.

PMID- 30090789
TI  - Relationship between serum gamma-glutamyltransferase activity and cardiometabolic
      risk factors in metabolic syndrome.
AB  - Objectives: The objective of this study was to examine the associations of serum
      gamma-glutamyltransferase (GGT) levels with the metabolic syndrome (MetS) and its
      components in Saudi adults. Methods: The study comprised 400 participants (70 men
      and 330 women), aged between 40 and 88 years, randomly selected from the medicine
      clinics at the King Abdulaziz University Hospital in Jeddah, Saudi Arabia, in a
      cross-sectional study design. A standardized questionnaire was used to determine
      demographics variables, general health, lifestyle habits, and medical history.
      Anthropometric and biochemical variables measurements were taken for all study
      participants. MetS was defined according to the American Heart
      Association/National Heart, Lung, and Blood Institute report, by the presence of
      abdominal obesity. Results: Higher means for triglycerides and insulin resistance
      indices (P < 0.0001) was found among those in the second, third, and fourth GGT
      quartiles as compared with their counterparts in the first quartile. McAuley
      index (beta = -0.239, P < 0.0001, 95% confidence interval: -4.1--1.5) was shown
      to be a major determinant of circulating GGT in a multivariate analysis.
      Conclusion: Elevated serum GGT could be a cardiometabolic risk factor either as a
      mediator of low-grade systemic inflammation and as a mediator of oxidative stress
      through mediation of extracellular glutathione transport into cells of organ
      systems.

PMID- 30090790
TI  - Burnout and depression among medical residents in the United Arab Emirates: A
      Multicenter study.
AB  - Introduction: Persistent imbalance between work demands and resources seems to be
      a crucial contributor to the development of burnout among medical professionals.
      Yet, it seems that Middle East is lacking studies analyzing psychological well
      being's of medical residents. Hence, we aimed to conduct a nationwide study to
      understand and address burnout and depression in medical residents in the UAE.
      Methods: A multicenter, cross-sectional study was designed to evaluate
      professional burnout and depression among medical residents to address the gap.
      Results: Our results indicate that 75.5% (216/286) of UAE medical residents had
      moderate-to-high emotional exhaustion (EE), 84% (249/298) had high
      depersonalization (DP), and 74% (216/291) had a low sense of personal
      accomplishment. In aggregate, 70% (212/302) of medical residents were considered
      to be experiencing at least one symptom of burnout based on a high EE score or a
      high DP score. Depression ranging from 6% to 22%, depending on the specialty was
      also noted. Noticeably, 83% (40/48) of medical residents who had high scores for
      depression also reported burnout. Conclusions: This study shows that burnout and
      depression are high among medical residents in UAE. There is a crucial need to
      address burnout through effective interventions at both the individual and
      institutional levels. Professional counseling services for residents will
      certainly be a step forward to manage resident burnout provided the social stigma
      associated with counseling can be eliminated with awareness. The work hour
      regulations suggested by the Accreditation Council for Graduate Medical Education
      partly provides a solution to improve patient safety and care quality. There is
      an urge to reconfigure the approach to medical training for the well-being of the
      next generation of physicians in the Arab world.

PMID- 30090791
TI  - Nonalbuminuric chronic kidney disease: A dominant presentation in noncommunicable
      disease population of rural central India.
AB  - Background: India has largest number of people with diabetes mellitus (DM), and
      hypertension (HTN) is expected to double in next 25 years, which are common
      causes of chronic kidney disease (CKD). The focus for prevention of end-stage
      renal disease has shifted to detection of the iceberg of DM and HTN and its
      adequate control. Prevalence studies of CKD in India rural community are lacking.
      Methodology: We did community-based cross-sectional study with 3 monthly
      diagnostic camps in adults >=20 years (n = 6278), from 13 villages for early
      detection of CKD in rural population around Sevagram in a group of
      noncommunicable disease (NCD) with DM, HTN, ischemic heart diseases (IHD), and
      stroke in year 2015-2016. Results: Study achieved 87% (5440/6278) coverage for
      albuminuria screening. Prevalence of CKD in NCD population was 19.6% (220/1121)
      where 86% (181/220) were nonalbuminuric CKD. Prevalence of persistent albuminuria
      in the study population was 0.8% (45/5440); in NCD population (DM, HTN, IHD, and
      stroke), it was 2.8% (31/1121). Prevalence of CKD was 19% in HTN and 18.9% in
      diabetes. The prevalence of nonalbuminuric versus albuminuric CKD was 17.1%
      versus 1.9% (9 times) in hypertensive individuals and 11.3% versus 7.5% (1.5
      times) in individuals with DM. Conclusion: Predominance of nonalbuminuric CKD in
      NCD participants raises suspicion of CKD with undetermined risk factors. Further
      studies are needed to find the prevalence of nonalbuminuric CKD in overall
      population and to find out if exposure of pesticides, chemical fertilizers over
      long duration play an important role in agrarian rural community.

PMID- 30090792
TI  - A case of hypertension with dementia: Common but underdiagnosed.
AB  - We report a case of a 55-year-old known hypertensive female who presented with
      features suggestive of dementia, which, on further workup unveiled background
      dyslipidemia and type 2 diabetes mellitus. An magnetic resonance imaging of the
      brain revealed findings suggestive of Binswanger's disease. This is a discussion
      of this unusual disease and its presentation and the differentials of this
      presentation which may be encountered in general clinical practice.

PMID- 30090793
TI  - Hyperacute liver injury following intravenous fluconazole: A rare case of dose
      independent hepatotoxicity.
AB  - Fluconazole is a triazole antifungal medication used in the treatment of various
      fungal infections. It is available in both oral and parenteral formulations.
      Liver damage has been reported with fluconazole use, but most commonly it is
      benign elevated liver transaminases. Acute liver failure (ALF) in fluconazole use
      is rare, with cases being reported sporadically in literature and large cohorts
      describing incidence rates of acute liver injury ranging from 0.0 to 31.6/10,000
      patients. We present a case of a 45-year-old African-American male with no
      history of liver disease who presented with superficial candidiasis and
      superimposed bacterial cellulitis. He was subsequently started on intravenous
      fluconazole and clindamycin. Shortly after he developed ALF and a drug-induced
      liver injury (DILI) was suspected. Fluconazole was stopped, and the clinical
      picture improved shortly afterward, leading to a diagnosis of fluconazole-induced
      ALF. Patient underwent laboratory and clinical evaluation to exclude competing
      etiologies of liver injury as well as a standardized assessment for causality and
      disease severity such as Roussel Uclaf Causality Assessment Method/Council for
      International Organizations of Medical Sciences score, which concluded a "Highly
      Probable" DILI, and a Naranjo score identifying adverse drug reaction (ADR) which
      concluded a "Definite ADR." Due to the severity of ALF and the routine use of
      fluconazole in clinical practice, clinicians should be aware that fluconazole can
      be a causative agent of ALF, even in low-risk populations.

PMID- 30090794
TI  - An uncommon cause of osteoporosis.
AB  - Osteoporosis in the younger age group is an important cause of morbidity.
      Prolactinoma is an uncommon but reversible cause of osteoporosis. The main
      mechanisms of osteoporosis in prolactinoma are reduced osteoblast activity and
      hypogonadism. A high index of suspicion is the key in diagnosis and management of
      this treatable entity.

PMID- 30090795
TI  - Prenatal diagnosis and management of fetal intra-abdominal umbilical vein varix.
AB  - Fetal intra-abdominal umbilical vein varix (FIUVV) is a rare pathology and
      suggests an enlargement of the umbilical vein. Prenatal diagnosis is done through
      meticulous ultrasound imaging. Management variables are the diameter of varix,
      presence or absence of turbulent flow, and fetal anomalies. Color and power
      Doppler ultrasound helps in diagnosis and follow-up and has a critical role in
      decision-making for intervention. Clinical guidelines for management are not
      clear. The adverse fetal outcome is usually associated with multiple
      malformations, turbulent flow, and thrombotic varix. This case study presents the
      prenatal diagnosis, obstetric management, and neonatal development of a fetus,
      diagnosed with FIUVV along with a brief review of the literature.

PMID- 30090796
TI  - Plasma cell leukemia.
AB  - We present a rare case report of a patient diagnosed with primary plasma cell
      leukemia (PCL) who presented with atypical signs and symptoms which acutely
      evolved into life-threatening multi-organ failure. This case raises questions
      regarding the latest diagnostic guidelines and therapeutic options in the
      management of acute PCL and reinforces the need for prompt treatment after
      diagnosis.

PMID- 30090797
TI  - A rare adverse drug reaction to escitalopram.
AB  - Selective serotonin reuptake inhibitors are considered to be low side effect
      profile drugs as compared to conventional antidepressants. The primary care
      physicians should be aware of the rare and depressing side effect of these drugs
      when they are prescribed in young, nonpregnant females. Mastalgia has been
      reported in <1% of the cases. Galactorrhea as an adverse drug reaction has been
      reported in very few case reports, and the frequency of this side effect is
      unknown.

PMID- 30090798
TI  - A fluttering coronary event.
AB  - Acute coronary syndrome (ACS) is a term used to describe a spectrum of diseases
      associated with sudden reduced blood flow to the heart. Coronary artery
      thromboembolism is recognized as an important nonatherosclerotic cause of acute
      myocardial infarctions in 2.9% of ACS cases, with a long-term outcome indicating
      that coronary embolism patients represent a high-risk subpopulation. There are
      various risk factors for developing a coronary thromboembolism, with atrial
      fibrillation being the most frequently reported cause. Herein, we are presenting
      a case of a 65-year-old female patient who presented to the emergency department
      with sudden-onset pressure-like chest pain diagnosed as ACS due to
      nonatherosclerotic thromboembolism secondary to atrial flutter.

PMID- 30090799
TI  - A case of liver cirrhosis and Chilaiditi syndrome with atypical pneumonitis.
AB  - Respiratory distress is very uncommon as a presenting symptom of Chilaiditi
      syndrome. Furthermore, pneumonia is not documented with the syndrome,
      compromising further to the distress. We describe a middle-aged man, chronic
      alcoholic, recently diagnosed with liver cirrhosis, presented with a 1-year
      history of slowly progressive breathlessness. Recently, he developed mild-to
      moderate hemoptysis and cough with aggravation of breathlessness. He did not have
      fever, chest pain, or orthopnea. He was cyanosed, requiring high-dose oxygen
      therapy. Later on, he stabilized with noninvasive ventilation. Chest imagings
      showed incidental Chilaiditi sign, liver cirrhosis, and atypical pneumonitis.
      With empirical antibiotics and high-dose steroid, he recovered completely but
      with baseline breathlessness. Here, we outline Chilaiditi syndrome as a rare
      association or manifestation of liver cirrhosis, and it can present with a
      respiratory compromise by both obstructive lung disease and atypical interstitial
      pneumonia. Early identification, vaccinations against common organisms, and
      possible early surgery may prevent morbidity and mortality of this type of
      patients.

PMID- 30090800
TI  - A comment on "lacunae in noncommunicable disease control program: Need to focus
      on adherence issues".

PMID- 30090801
TI  - Wonca Rural South Asia and WONCA SAR conference: All about empowering rural
      health care.

PMID- 30090802
TI  - Coxsackie encephalitis in a child in Western India: Correspondence.

PMID- 30090803
TI  - Sitagliptin-induced diffuse alveolar hemorrhage mimicking pulmonary edema.

PMID- 30090804
TI  - Profession's future: A concerned physician easily available.

PMID- 30090805
TI  - Purple urine bag as indicator of multidrug-resistant vulvar abscess: Lessons for
      primary caregivers.

PMID- 30090806
TI  - Can The MobleesTM Move Canadian Children? Investigating the Impact of a
      Television Program on Children's Physical Activity.
AB  - Background: The effects of messaging about physical activity and sedentary
      behavior purposefully integrated into children's TV programming on children's
      behavior is unknown. The Moblees is a Canadian childrens' show that explicitly
      promotes physical activity. Two studies were conducted to (1) examine whether
      children were more physically active when watching a Moblees episode, and (2)
      explore parental perceptions of the show. Methods: Study 1 was an experimental
      study with 21 families randomized to watch an episode of The Moblees vs. a
      control condition. Movement was assessed through accelerometry and observation. A
      Chi-square test was used to compare the direct observation proportions of
      children sitting between intervention and control conditions. Independent t-tests
      were performed to examine the differences in total vector magnitude counts
      between the experimental and control groups. Study 2 was an online cross
      sectional study with 104 parent/child dyads that included viewing an episode of
      The Moblees. To identify correlates and predictors of parent-reported child PA
      during viewing The Moblees compared to other TV programs, Pearson's correlations
      and a linear regression were calculated, respectively. Results: In study 1 there
      was a significant association between condition and whether or not children
      remained sitting chi2 = 55.96, p < 0.001. There was a significant difference in
      counts between the two conditions, t(13, 61) = 2.29, p < 0.05. Children
      randomized to the experimental group (i.e., Moblees) moved more compared to
      control. In study 2 the majority (76%) of parents reported that their child
      engaged in some physical activity during viewing. Parent encouragement during
      viewing was the strongest predictor of child physical activity while viewing
      (beta = 0.30, p < 0.01). Conclusion: Television content that includes messaging
      about physical activity and sedentary behavior, and positive portrayals of
      physical activity may influence the physical activity of young children. Although
      the benefits of such modest movement are not clear without further evidence of
      accumulation over time and/or transfer to other settings, television programming
      might provide a far reaching medium for knowledge translation.

PMID- 30090807
TI  - Ion-Exchange Chromatography Coupled With Dynamic Coating Capillary
      Electrophoresis for Simultaneous Determination of Tropomyosin and Arginine Kinase
      in Shellfish.
AB  - Tropomyosin (TM) and arginine kinase (AK) are known as two major allergens in
      seafood. For the first time, we demonstrate a newly developed ion-exchange
      chromatography coupled with dynamic coating capillary electrophoresis (IEC-DCCE)
      method to simultaneously analyze the TM and AK in shellfish. First, we have
      optimized the procedure of IEC for simple enrichment of TM and AK crude extract.
      By using 30 mM borate-borax at pH 9.0 with 0.3% (v/v) Tween-20 as a dynamic
      coating modifier for capillary electrophoresis (CE) separation, the migration
      time, separation efficiency and electrophoretic resolution greatly improved. The
      limits of detection (LOD) were 1.2 MUg mL-1 for AK and 1.1 MUg mL-1 for TM (S/N =
      3), and the limits of quantification (LOQ) were 4.0 MUg mL-1 for AK and 3.7 MUg
      mL-1 for TM (S/N = 10). The recovery of AK ranged from 91.5 to 106.1%, while that
      of TM ranged from 94.0 to 109.5%. We also found that only when the concentrations
      of AK and TM were above LOD reported here, these proteins can stimulate human
      mast cell (LAD2) degranulation. Finally, the use of IEC-DCCE to analyze fresh
      shellfish samples highlights the applicability of this method for the
      simultaneous detection of these allergens in complex food systems.

PMID- 30090809
TI  - A Conceptual Framework for Optimizing Blood Matching Strategies: Balancing
      Patient Complications Against Total Costs Incurred.
AB  - Alloimmunization is currently the most frequent adverse blood transfusion event.
      Whilst completely matched donor blood would nullify the alloimmunization risk,
      this is practically infeasible. Current matching strategies therefore aim at
      matching a limited number of blood groups only, and have evolved over time by
      systematically including matching strategies for those blood groups for which
      (serious) alloimmunization complications most frequently occurred. An optimal
      matching strategy for controlling the risk of alloimmunization however, would
      balance alloimmunization complications and costs within the entire blood supply
      chain, whilst fulfilling all practical requirements and limitations. In this
      article the outline of an integrated blood management model is described and
      various potential challenges and prospects foreseen with the development of such
      a model are discussed.

PMID- 30090808
TI  - Advances in the Development of Shape Similarity Methods and Their Application in
      Drug Discovery.
AB  - Molecular similarity is a key concept in drug discovery. It is based on the
      assumption that structurally similar molecules frequently have similar
      properties. Assessment of similarity between small molecules has been highly
      effective in the discovery and development of various drugs. Especially, two
      dimensional (2D) similarity approaches have been quite popular due to their
      simplicity, accuracy and efficiency. Recently, the focus has been shifted toward
      the development of methods involving the representation and comparison of three
      dimensional (3D) conformation of small molecules. Among the 3D similarity
      methods, evaluation of shape similarity is now gaining attention for its
      application not only in virtual screening but also in molecular target
      prediction, drug repurposing and scaffold hopping. A wide range of methods have
      been developed to describe molecular shape and to determine the shape similarity
      between small molecules. The most widely used methods include atom distance-based
      methods, surface-based approaches such as spherical harmonics and 3D Zernike
      descriptors, atom-centered Gaussian overlay based representations. Several of
      these methods demonstrated excellent virtual screening performance not only
      retrospectively but also prospectively. In addition to methods assessing the
      similarity between small molecules, shape similarity approaches have been
      developed to compare shapes of protein structures and binding pockets.
      Additionally, shape comparisons between atomic models and 3D density maps allowed
      the fitting of atomic models into cryo-electron microscopy maps. This review aims
      to summarize the methodological advances in shape similarity assessment
      highlighting advantages, disadvantages and their application in drug discovery.

PMID- 30090810
TI  - Increased Ratio of Non-mercaptalbumin-1 Among Total Plasma Albumin Demonstrates
      Potential Protein Undernutrition in Adult Rats.
AB  - The redox state of plasma albumin shifts in response to dietary protein intake in
      growing rats, and the shift is more sensitive than that of plasma albumin level,
      a classical marker of protein nutritional status. While it has been suggested
      that plasma albumin redox state could be useful as a novel marker of protein
      nutritional status, the above animal model is highly sensitive to dietary protein
      intake and the observation may not be extrapolated widely to humans. This study
      aimed to investigate whether albumin redox state also reflects protein
      nutritional status in adult rats, which have a lower dietary protein requirement
      and are less responsive to protein intake. Male adult rats were placed on AIN-93M
      diet (14% casein), or AIN-93M-based low protein diets (10 or 5% casein) ad
      libitum for 24 weeks. Whereas there was no significant difference in body weight
      between the groups at the end of the experimental period, the 5% casein diet
      group had the smallest gastrocnemius muscle weight among the groups, which was
      significantly lower than that of the 10% casein diet group. Plasma albumin level
      was also lower in the 5% casein diet group compared with the other groups, but
      the differences were limited and inconsistent during the experimental period.
      Among the albumin redox isoforms such as mercaptalbumin, non-mercaptalbumin-1,
      and non-mercaptalbumin-2, the ratio of non-mercaptalbumin-1 among total albumin
      was significantly higher in the 5% casein diet group, and the increase remained
      constant throughout the experimental period. Increased non-mercaptalbumin-1 ratio
      would thus demonstrate the presence of potential protein undernutrition in adult
      rats, as manifested only by a decreased gain in a specific type of skeletal
      muscle; non-mercaptalbumin-1 among total albumin ratio could be useful as a
      robust marker of protein nutritional status, contributing to prevention of
      protein undernutrition-related diseases such as frailty and sarcopenia.

PMID- 30090812
TI  - Mortality Rate and Predicting Factors of Traumatic Thoracolumbar Spinal Cord
      Injury; A Systematic Review and Meta-Analysis.
AB  - Objective: To estimate the summation of mortality rate and the contributing
      factors in patients with traumatic thoracolumbar spinal cord injuries (TLSCI).
      Methods: A systematic search of observational studies that evaluated the
      mortality associated with TLSCI in MEDLINE and EMBASE was conducted. The study
      quality was evaluated using a modified quality assessment tool previously
      designed for observational studies. Results: Twenty-four observational studies
      involving 11,205 patients were included, published between January 1, 1997, and
      February 6, 2016. Ten studies were of high quality, thirteen were of moderate
      quality, and one study was of low quality. Seventeen reports described risk
      factors for mortality and eleven of these studies used a multiple regression
      models to adjust for confounders. The reported mortality rate ranged from 0 to
      37.7% overall and between 0 and 10.4% in-hospital. The sum of mortality for in
      hospital, 6-month, and 12-month were 5.2%, 26.12%, 4.3%, respectively. The
      mortality at 7.7 years follow-up was 10.07% and for 14 years follow-up reports
      ranged from 13.47% to 21.46%. Associated data such as age at injury, male to
      female ratio, pre-existing comorbidities, concomitant injuries, duration of
      follow-up, and cause of death have been underreported in studies investigating
      the mortality rate after TLSCI. Conclusion: There is no study was found that
      accurately assessed mortality in the thoracolumbar spine, while there is general
      agreement that traumatic thoracolumbar spinal cord injuries are important.

PMID- 30090811
TI  - Fumarase: From the TCA Cycle to DNA Damage Response and Tumor Suppression.
AB  - Fumarase is an enzyme of the tricarboxylic acid (TCA) cycle in mitochondria, but
      in recent years, it has emerged as a participant in the response to DNA double
      strand breaks (DSBs) in the nucleus. In fact, this enzyme is dual-targeted and
      can be also readily detected in the mitochondrial and cytosolic/nuclear
      compartments of all the eukaryotic organisms examined. Intriguingly, this
      evolutionary conserved cytosolic population of fumarase, its enzymatic activity
      and the associated metabolite fumarate, are required for the cellular DNA damage
      response (DDR) to double-strand breaks. Here we review findings from yeast and
      human cells regarding how fumarase and fumarate may precisely participate in the
      DNA damage response. In yeast, cytosolic fumarase is involved in the homologous
      recombination (HR) repair pathway, through its function in the DSB resection
      process. One target of this regulation is the resection enzyme Sae2. In human
      cells, fumarase is involved in the non-homologous end joining (NHEJ) repair
      pathway. Fumarase is phosphorylated by the DNA-dependent protein kinase (DNA-PK)
      complex, which induces the recruitment of fumarase to the DSB and local
      generation of fumarate. Fumarate inhibits the lysine demethylase 2B (KDM2B),
      thereby facilitating the dimethylation of histone H3, which leads to the repair
      of the break by the NHEJ pathway. Finally, we discuss the question how fumarase
      may function as a tumor suppressor via its metabolite substrate fumarate. We
      offer a number of models which can explain an apparent contradiction regarding
      how fumarate absence/accumulation, as a function of subcellular location and
      stage can determine tumorigenesis. Fumarate, on the one hand, a positive
      regulator of genome stability (its absence supports genome instability and
      tumorigenesis) and, on the other hand, its accumulation drives angiogenesis and
      proliferation (thereby supporting tumor establishment).

PMID- 30090813
TI  - Healing Effects of Dried and Acellular Human Amniotic Membrane and Mepitelas for
      Coverage of Skin Graft Donor Areas; A Randomized Clinical Trial.
AB  - Objective: To compare the healing effects of dried and acellular human amniotic
      membrane and Mepitel for coverage of split-thickness graft donor site (STGDS).
      Methods: Twenty patients who underwent STGDS regeneration surgery in identical
      anatomic regions were enrolled in this randomized controlled clinical trial
      conducted in Hazrate Fatemeh hospital (Iran). Patients were randomly assigned in
      3 groups of wound dressing; group A by Mepitel, group B AmiCare (Dried amniotic
      membrane) and group C OcuReg-A (Acellular amniotic membrane). Re-epithelization
      rate (healing time), pain sensation, scar formation and infection rate were
      assessed till complete healing was achieved. Results: Our results showed no
      significant difference between Amicare, OcuReg-A and Mepitel in the features
      analyzed by us including: Re-epithelization rate (healing time) P value; 0.573,
      Pain sensation P value: day 4 th: 0.131, day8 th: 0.93 and day 12 th: 0.365, Scar
      formation P value>0.05and Infection rate. Conclusion: Our findings confirmed the
      safety and efficacy of AmiCare (dried amniotic membrane) and OcuReg-A (Acellular
      amniotic membrane) in treatment of split-thickness donor site in comparison with
      Mepitel as a standard wound dressing. Trial registration number:
      IRCT201511118177N12.

PMID- 30090814
TI  - The Effects of Chicken Embryo Brain Extract on Sciatic Nerve Regeneration of Male
      Rat; An Experimental Study.
AB  - Objective: To determine the effects of chicken embryo brain extract (BE) on
      transects sciatic nerve in male rats. Methods: Thirty adult male Sprague-Dawley
      rats weighing 200 to 250 g, were randomized into three groups treated with (1)
      sham surgery, (2) normal saline (NS), and (3) brain extract (BE). The BE was
      taken from incubating chick embryos at day 8. The sciatic nerve was exposed and
      sharply transected at the mid thigh level. Immediate epineurial repair was then
      performed. The BE treated animals were given 400 ul/kg of the chick embryo BE
      intraperitoneal, once daily, for 2 weeks. All animals were evaluated by sciatic
      functional index (SFI), electrophysiology, histology, and immunohistochemistry at
      days 28, 90 after surgery. Results: The mean SFI difference between BE and NS
      groups at days 28, 60 and 90 after surgery was statistically significant
      (p=0.086). The mean number of myelinated fibers in the BE group was significantly
      greater than that of the NS group on days 28 and 90 after surgery (p=0.034). At
      days 28 and 90 after surgery, the mean nerve conduction velocity (NCV) in the BE
      group was significantly faster than that of the NS group (p=0.041). Conclusion:
      These results indicate for the first time that chick embryo brain extract can
      enhance peripheral nerve regeneration in rat.

PMID- 30090815
TI  - Interaperitoneal Administration of Alphalpha-Tocopherol Loaded Nanoparticles
      Improves Ischemia-Reperfusion Injury in Rat Ovaries Torsion and Detorsion Model.
AB  - Objective: To investigate effects of intraperitoneally administration of alpha
      tocopherol loaded nanoparticles (TNP) on ischemia-reperfusion injury in ovaries.
      Methods: Thirty-five healthy female Wistar rats ~250g were randomized into seven
      experimental groups (n = 5): Group SHAM: The rats underwent only laparotomy.
      Group Ischemia: A 3- hour ischemia only. Group I/R: A 3-hour ischemia and a 3
      hour reperfusion. Group I/T: A 3-hour ischemia only and 100 mg/kg intraperitoneal
      administration (IP) of alpha-tocopherol 2.5 hours after induction of ischemia.
      Group I/R/T: A 3-hour ischemia, a 3-hour reperfusion and 100 mg/kg IP of alpha
      tocopherol 2.5 hours after induction of ischemia. Group I/TNP: A 3-hour ischemia
      only and 1 mg/kg IP of TNP 2.5 hours after induction of ischemia. Group I/R/TNP:
      A 3-hour ischemia, a 3-hour reperfusion and 1 mg/kg IP of TNP 2.5 hours after
      induction of ischemia. Results: Animals treated with alphaTNP showed
      significantly ameliorated development of ischemia and reperfusion tissue injury
      compared to those of other groups (p=0.001). The significant higher values of
      SOD, tGSH, GPO, GSHRd and GST were observed in I/R/NC animals compared to those
      of other groups (p=0.001). Damage indicators (NOS, MDA, MPO and DNA damage level)
      were significantly lower in I/R/NC animal compared to those of other groups
      (p=0.001). Conclusion: Intraperitoneal administration of TNP could be helpful in
      minimizing ischemia-reperfusion injury in ovarian tissue exposed to ischemia.

PMID- 30090816
TI  - Massive Blood Transfusions and Outcomes in Trauma Patients; An Intention to Treat
      Analysis.
AB  - Objective: To determine if there exists an upper limit for amount of blood
      transfused in trauma patients before it reaches a point of futility. Methods: A
      prospective cohort study was conducted on 131 patients who received massive blood
      transfusion (MBT), defined as 10 U or higher of PRBCs received in the initial 24
      hours. Data collected from a Level II trauma center registry were used to analyze
      reports of adult patients from July 2014 to 2017. Cohorts were divided by amount
      of blood received - 0 to 9 U, 10-19 U, 20 to 29 U, 30-39 U, 40 U or higher - odds
      ratio for mortality and p-values for mean Injury Severity Score and overall
      hospital length of stay were calculated for each group. Results: Odds ratios for
      massive blood transfusion groups from 10 units to 39 units each contained the
      null value, while our 40 units and above group did not (OR 12.52, 95% CI 1.3
      117.7). Conclusion: Although this study is limited by its sample size, these
      results suggests that 40 units of PRBCs may be a threshold at which survival
      rates begin to decrease significantly.

PMID- 30090817
TI  - Experience and Availability of Pelvic Binders at Swedish Trauma Units; A
      Nationwide Survey.
AB  - Objective: To assess availability, experience, and knowledge about the Pelvic
      Circumferential Compression Device (PCCD) in Sweden. Methods: A telephone
      interview with the current on-call trauma doctors at all trauma units in Sweden
      was conducted. After a short presentation and oral consent, the doctors were
      asked to answer four short questions. We asked the doctors to answer whether they
      knew if they had PCCDs available in their emergency room, how many times had they
      applied a PCCD, which is the correct level of application for a PCCD, and if a
      PCCD can stop arterial bleeding. Results: The on-call trauma doctors at the nine
      University hospitals, twenty-two General hospitals and twenty-one District
      General hospitals, with response rate of 100%, were interviewed. Availability of
      PCCD was 85 % and there was no difference between hospital types (p=0.546). In
      all hospitals 29/52 (56%) of those interviewed had used a PCCD at least once.
      There were significantly more doctors that had used a PCCD at least once in the
      University hospitals (8/9), compared to General hospitals (13/22) and District
      General hospitals (8/21) (p=0.034). A total of 43/52 (83 %) doctors defined the
      greater trochanters as the correct level of application for a PCCD. No difference
      was found when comparing hospitals (p=0.208). Only 22/52 (42 %) of doctors
      answered that a PCCD could not stop an arterial bleeding. No difference was found
      between hospitals (p=0.665). Conclusion: Less than half of the doctors knew that
      a PCCD cannot stop arterial bleeding, while the majority knew the correct level
      of application of a PCCD.

PMID- 30090818
TI  - Predictors of Incidence of Fall in Elderly Women; A Six-Month Cohort Study.
AB  - Objective: To determine the incidence and predictive factors of the falls in
      elderly women in Northern Iran. Methods: A total of 717 elderly women aged 60
      years and above in Amirkola, Northern of Iran participated in this study. Age,
      history of falls during the 12 months leading to the study, accompanying
      diseases, status of balance, cognitive status, orthostatic hypotension, state of
      depressive symptoms, strength of quadriceps muscles and serum vitamin D level
      were assessed as independent variables during baseline measurement. Incidence of
      fall (dependent variable) was recorded during a six-month follow-up period.
      Results: Of the participants, 7.8% had experience of fall, out of which 50.0%
      experienced it once, 25.0% twice, and the rest three times or more. With aging,
      the incidence of orthostatic hypotension also increased and symptomatic
      depression became aggravated. In the final model, the variables of the number of
      accompanying diseases (RR=1.78, 95% CI: 1.00-3.18), severe cognitive impairment
      (RR=12.70, 95% CI: 3.05-52.86), and depressive symptoms (RR=3.19, 95% CI: 1.48
      6.86) remained as strong associated variables for incidence of fall. Conclusion:
      With increasing severity of depressive symptoms and cognitive impairment along
      with the comorbidities, incidence of fall also increases in the elderly. Thus,
      psychological aspects of the elderly and comorbidities in this group should be
      taken care of seriously.

PMID- 30090819
TI  - Epidemiologic Aspects of Overall Injuries in Hamadan Province; A Six-Year
      Registry-Based Analysis.
AB  - Objective: To investigate the epidemiological aspects of all-cause injuries in
      Hamadan province during a 6-year period. Methods: We conducted a cross-sectional
      study on injured subjects admitted to private or governmental hospitals in
      Hamadan province during March 2009 to March 2015. The epidemiological
      characteristics were retrieved from a registry-based system including gender,
      residency, injury mechanism and date of injury occurrence, outcome of
      hospitalization (full recovery/disability/death). Results: Totally, 135,925
      hospitalized injured cases were recorded. The majority of cases were male (72.6%)
      and were occurred in urban areas (60%), about 40% of patients were in 20-34
      years' age group, and the highest proportion (30.13%) of injuries occurred in
      summer. Logistic regression showed that the odds of disability vs. recovery was
      significantly higher in rural areas [Adjusted odds ratio (AOR) =3.42] and the
      odds of death vs. recovery was higher among male gender (AOR=1.46). In addition,
      comparing to the 0-4-year age-group, odds of death were significantly higher in
      middle aged and elderly victims. Conclusion: Our findings showed that middle age
      groups, male gender and urban area increase the odds of death. Injured males and
      old age subjects had the highest odds of death and out of residential area
      injuries were common cause of leading death injuries.

PMID- 30090820
TI  - Epidemiology of Animal Bites and Associated Factors with Delay in Post-Exposure
      Prophylaxis; A Cross-Sectional Study.
AB  - Objective: To address the epidemiology of animal bites and associated factors
      with delay in post-exposure prophylaxis (PEP) in Nahvand district, western Iran.
      Methods: Data were obtained from Rabies Treatment Center (RTC) in Nahavan
      district from March 2015 to March 2017. All of referred cases to RTC include 1448
      cases of animal bites using the census method were recruited. Epidemiological
      profile of participants was demonstrated using descriptive statistics and
      determinants of PEP was addressed by logistic regression model. Results: The
      majority of victims were males 1167(80.5%). superficial bites were more prevalent
      than deep status injuries (1145(79.0%) VS. 303(20.9%)). The biting rate differed
      according to season in the period of the study (p<0.001). Cases who experienced
      animal biting in the autumn was more likely to refer timely for PEP than cases in
      spring season (OR, 0.39; 95% CI: 0.26 - 0.59, p<0.001). Conclusion: Our findings
      addressed the pattern of potential delays in PEP including the role of season.
      Local authorities of Nahavand district should considered preventive activities
      and educational interventions to reduce animal biting and provide timely
      prophylaxis.

PMID- 30090821
TI  - Trends of Suicide Attempts and Completed Suicide in Ilam Province of Iran; A
      Demographic Analysis Study.
AB  - Suicide is a serious public health concern in the world. Epidemiologists are
      considered the mainstay of the management of problem. The purpose of this study
      was to investigate the trend of suicide (attempts and completed) by age and
      gender in a 6-year time period and to compare the suicide rates between in age
      and gender groups in Ilam. In this cross-sectional study, a total of number of
      suicidal attempts during a 6-year period from 2011 to 2016 were recorded. The
      data were derived from the systematic registration suicide data (SRSD) which
      collects official statistics from the Ilam University of Medical Sciences.
      Suicide rate in period of the study in men was reported to be 24.0 in 2011 to
      17.9 in 2016 per 100,000 populations; also this rate in women was between 16.2 in
      2011 to 7.3 in 2016 per 100,000 populations. Trend analysis revealed a decreasing
      trend (r= -0.82, p=.043), in attempts, as well as completed suicides (r= -0.53,
      p=.048). The current data demonstrated a decreasing trend in both attempts and
      completed suicide rates from 2011 to 2016. Also we found that the rate of
      completed suicide in all age groups were higher in men compared to women.

PMID- 30090822
TI  - Hyperthermia and Rigidity Following Overdose of an Unknown Drug; A Case Report
      and Literature Review.
AB  - Drug induced hyperthermia is a rare presentation which can rapidly lead to gross
      metabolic abnormality and death. These presentations are further complicated by
      the wide range of potentially causative agents. We present a case of rigidity and
      hyperthermia, following overdose of an initially unknown substance leading to
      challenging management decisions in the Emergency Department. This case was later
      identified as Serotonin Syndrome. The patient presented with trismus which was
      managed with rapid sequence induction of anaesthesia to allow airway protection.
      On extubation a significant degree of laryngeal oedema complicated weaning, a
      possible complication of Serotonin Syndrome not previously described in the
      literature. We discuss the pathophysiology of Serotonin Syndrome, important
      differentials and practical considerations in managing hypertonicity of unknown
      origin in a young person.

PMID- 30090823
TI  - Intracerebral Hemorrhage Secondary to Scorpion Toxin in the Northwest of
      Argentina; A Case Report.
AB  - Scorpionism is the clinical picture resulting from the inoculation of scorpion
      venom. It is considered a major public health problem, especially in countries
      with low resources and tropical or subtropical climate. Poisoning can be fatal
      especially in the first hours due to respiratory and / or cardiovascular
      collapse. The compromise of the central nervous system (CNS) is infrequent but
      varied and complex, being able to be triggered due to multiple and different
      neurotoxic properties of the toxin. We report here a severe case of poisoning
      with cardiovascular and neurological compromise in an endemic region of
      Argentina. After cardiorespiratory stabilization, neurological deterioration is
      detected secondary to intracerebral hemorrhage that required surgery and
      multimodal neuromonitoring. The outcome was fatal due to multiple neurological
      and systemic complications. Scorpion sting poisoning is a true neurologic and
      neurosurgical life-threatening emergency.

PMID- 30090824
TI  - Handlebar Hernia with Triple Herniation and Perforation: A Case Report and
      Literature Review.
AB  - Blunt trauma abdomen is a very common entity but traumatic abdominal wall hernia
      is not that common. Herniation through abdominal wall usually occurs following
      trauma with seat belt, motor cycle, bicycle handle bar etc. Handlebar hernia is a
      less known variety of traumatic abdominal wall hernia as a consequence of injury
      with handlebar of a bicycle. It is difficult to diagnose and one should have high
      index of suspicion. Management in traumatic abdominal wall hernia is
      individualized based on various factors. We herein present an interesting case of
      a14-year-old boy, who sustained blunt trauma abdomen from bicycle handlebar
      leading to triple herniation and perforation of the small bowel and hematoma of
      the mesentery. Patient was resuscitated and operated with a favorable outcome.
      Blunt trauma abdomen is a very common and the possibility of traumatic abdominal
      wall hernia should always be borne in mind.

PMID- 30090825
TI  - Femoral Shaft Fracture during Bungee Jump: A Case Report and Literature Review.
AB  - Bungee jumping is a recreational sport that is accepted to carry a level of risk.
      We present the case of a femoral fracture sustained during bungee jumping and
      examine the published literature on bungee jumping-related injuries. A previously
      well 31-year old female performed a 200ft bungee jump from a crane. The apparatus
      was performed as expected and documented on the bystander video footage. As the
      bungee-cord became taut for the second time, there was an audible crack with
      accompanying scream. A closed, neurovascularly-intact injury was sustained to her
      right thigh. Radiographs revealed a comminuted mid-diaphyseal spiral femoral
      fracture, which was treated with intra-medullary nail fixation the following day.
      Following loss of position with proximal fragment flexion, the intramedullary
      nail was revised with open reduction and cerclage wiring 6 weeks later.
      Progression to clinical and radiological union was uneventful. Fatalities in
      bungee jumping are generally secondary to trauma as a result of equipment
      malfunction, user error, or related to pre-existing co-morbidity2. As no records
      are kept on bungee jumping injuries in the UK, reliable statistics are not
      available regarding the relative risks of this sport. We conclude that incidence
      of bungee jumping injuries is likely to remain low, but consider that improved
      recording of bungee jumping-related injury data will allow providers to give
      customers a realistic quantification of risk before engaging in this sport.

PMID- 30090826
TI  - Diaphragmatic Herniation of Ruptured Right Lobe of Liver with Hypertrophied Left
      Lobe.

PMID- 30090827
TI  - Left Ventricular Pseudoaneurysm: An Overview of Diagnosis and Management.
AB  - Left ventricular pseudoaneurysm is a rare but life-threatening disorder that is
      frequently reported secondary to myocardial infarction or cardiac surgery. In
      this article, we chronicle the case of a patient with no prior risk factors who
      presented with a 2-week history of nonexertional atypical left chest pain. Apical
      2-chamber transthoracic echocardiography revealed an unexpected outpouching of
      basal inferoseptal wall of the left ventricle, which had a narrow neck and
      relatively wide apex. The patient was diagnosed with left ventricular
      pseudoaneurysm and medical therapy was initiated. He refused to undergo the
      surgical intervention and subsequently, he was discharged from the hospital in
      stable condition. This article illustrates that physicians should be vigilant for
      atypical presentations of left ventricular pseudoaneurysm, and a high index of
      suspicion should be maintained for this stealth killer while performing
      appropriate diagnostic imaging. Additionally, we review the currently available
      approaches to diagnosis and management in these patients.

PMID- 30090828
TI  - Clinical Evaluation of an Arthroscopic Knotless Suprapectoral Biceps Tenodesis
      Technique: Loop 'n' Tack Tenodesis.
AB  - Background: Pathology of the long head of the biceps tendon is a well-known cause
      of shoulder pain that is commonly managed with arthroscopic suprapectoral biceps
      tenodesis when conservative treatment fails. Purpose: To present an arthroscopic
      knotless suprapectoral biceps tenodesis technique known as "Loop 'n' Tack"
      tenodesis and to report the clinical outcomes of patients with a minimum 2 years
      of follow-up. Study Design: Case series; Level of evidence, 4. Methods: A
      retrospective review of all patients who had undergone Loop 'n' Tack tenodesis
      between January 2009 and May 2014 was completed. Charts were reviewed, and
      patients were contacted for demographic data, time from surgery, concomitant
      procedures, and workers' compensation status, as well as visual analog scale for
      pain, American Shoulder and Elbow Surgeons (ASES), Single Assessment Numeric
      Evaluation, and University of California, Los Angeles (UCLA) scores. Results:
      Complete follow-up evaluations were performed for 59 of 68 patients (87%). Mean
      follow-up was 43 months. A majority (88%) of patients had at least 1 additional
      procedure performed at the time of biceps tenodesis. The mean ASES shoulder score
      improved from 42.6 preoperatively to 91.0 postoperatively (P < .001), and 54 of
      59 patients (91.5%) had a good/excellent outcome, with a UCLA shoulder score >27
      and ASES shoulder score >70. Three patients (5%) reported biceps cramping pain
      with overuse, and 2 (3.3%) reported intermittent anterior shoulder pain. No
      patients had developed a "Popeye" deformity at final clinical examination, and
      97% reported that they were overall satisfied with the procedure. Conclusion: The
      Loop 'n' Tack tenodesis technique results in a high rate of patient satisfaction,
      significant improvement in shoulder outcome scores, and a low incidence of
      postoperative pain, with no reoperations for biceps-related pathology.

PMID- 30090829
TI  - Injuries in the Chinese Arena Football League: American Versus Chinese Players.
AB  - Background: Arena football is an indoor version of American football played in
      indoor arenas on a smaller field with 8 players per team. Only 1 study has
      evaluated injury rates in arena football, and no study had compared 2 distinct
      cohorts of players. Purpose/Hypothesis: The purpose of this study was to evaluate
      and compare injury rates in American versus Chinese athletes in the Chinese Arena
      Football League. Our hypothesis was that the rate of significant injuries (>=7
      days of time lost from play) would be statistically significantly higher in
      Chinese athletes. Study Design: Cohort study; Level of evidence, 2. Methods: Each
      of the 6 teams included in this study comprised 11 American and 11 Chinese
      athletes, for a total of 132 included athletes (66 Chinese, 66 American). All
      players stayed in the same hotel, trained and played in the same facilities, and
      were covered by the same medical staff. A total of 18 games were played
      consecutively in 6 cities from October 1 to November 6, 2016. At least 4 Chinese
      players had to be on the field for each team at all times during game play.
      Results: American athletes were significantly older, taller, and heavier than
      Chinese athletes. The total exposure was 759 athlete-hours, and there were 80
      reported injuries, with 74 (92.5%) occurring during games (overall injury rate,
      105.4 injuries per 1000 athlete-hours). For American athletes, the exposure was
      387 athlete-hours with 38 injuries observed, and the injury rate was 98.2
      injuries per 1000 athlete-hours. For Chinese athletes, the exposure was 372
      athlete-hours with 42 injuries observed, and the injury rate was 112.9 injuries
      per 1000 athlete-hours. There was no statistically significant difference in
      exposure or overall injury rate between American and Chinese athletes. The rate
      of significant injuries was 30.3 per 1000 athlete-hours; there were 17 such
      injuries in Chinese athletes compared with 6 such injuries for American athletes.
      The rate of significant injuries was 45.7 (Chinese) and 15.5 (American) injuries
      per 1000 athlete-hours, and the relative risk for Chinese versus American
      athletes for significant injuries was 3.0 (95% CI, 1.2-7.8; P = .019) . Binary
      logistic regression models were utilized to analyze whether the baseline
      variables (height, weight, body mass index, age, years of experience, and
      nationality) were potential predictors for an injury, and only years of
      experience (odds ratio, 1.147 [95% CI, 1.034-1.271]; P = .009) was found to be
      associated with severe injuries (>21 days of time loss). Conclusion: The overall
      risk of injuries was similar between Chinese and American athletes, but Chinese
      athletes showed statistically higher rates of significant injuries than their
      American counterparts. Years of experience was the only factor that was
      associated with severe injuries. As professional sports become more global,
      medical personnel must take into account the distinct differences and levels of
      experience between the national and international professional athletes. The
      results of this study will be used to make recommendations to develop preventive
      training measures, including techniques to improve tackling.

PMID- 30090830
TI  - Is Edema at the Posterior Medial Tibial Plateau Indicative of a Ramp Lesion? An
      Examination of 307 Patients With Anterior Cruciate Ligament Reconstruction and
      Medial Meniscal Tears.
AB  - Background: Medial meniscal tears are commonly seen during anterior cruciate
      ligament reconstruction (ACLR). A subset of these injuries includes posterior
      meniscocapsular junction or "ramp" tears. One criterion that may correlate with a
      ramp lesion is the presence of posterior medial tibial plateau (PMTP) edema.
      Purpose: To compare patients with ramp lesions to patients with nonramp (meniscal
      body) medial meniscal tears and correlate PMTP edema on preoperative magnetic
      resonance imaging (MRI) to the incidence of ramp tears. Study Design: Case
      control study; Level of evidence, 3. Methods: From 2006 to 2016, a total of 852
      patients underwent ACLR and had operative reports available for review. Age, sex,
      laterality, mechanism of injury (contact/noncontact), sport, revision procedure,
      multiligament injury, time to MRI, and time to surgery were recorded.
      Preoperative MRI scans were reviewed for PMTP edema using axial, coronal, and
      sagittal T2 and proton-density sequences. Differences between groups were
      analyzed using a 2-sample t test and chi-square test. Univariate and multivariate
      logistic regression models examined correlations with tear type. Results:
      Overall, 307 patients had medial meniscal tears identified during ACLR (127 ramp
      lesions, 180 meniscal body lesions). The ramp group was 7.5 years younger than
      the meniscal body group (P < .01). The groups were not different regarding sex,
      contact injury, revision surgery, laterality, or multiligament injury. Patients
      with delayed ACLR were significantly more likely to have a meniscal body tear
      than a ramp lesion (odds ratio, 3.3 [95% CI, 1.9-5.6]; P < .01). The sensitivity
      of PMTP edema for a ramp tear was 66.3%, and 54.5% of patients with ACLR and a
      medial meniscal tear had PMTP edema. Patients with PMTP edema were significantly
      more likely to have a ramp tear than a meniscal body tear (odds ratio, 2.1 [95%
      CI, 1.1-4.1]; P < .03). Conclusion: The overall incidence of ramp tears in
      patients undergoing ACLR was 14.9%, and these tears were more prevalent in
      younger patients. Meniscal body tears were significantly more likely than ramp
      tears with delayed ACLR. In patients undergoing ACLR with an associated medial
      meniscal tear, the presence of PMTP edema demonstrated significantly greater odds
      for ramp lesions compared with meniscal body tears.

PMID- 30090831
TI  - Do Articular-Sided Partial-Thickness Rotator Cuff Tears After a First-Time
      Traumatic Anterior Shoulder Dislocation in Young Athletes Influence the Outcome
      of Surgical Stabilization?
AB  - Background: Because of the high risk for redislocations after a first-time
      traumatic anterior shoulder dislocation with conservative treatment, recent
      publications have recommended early arthroscopic intervention, especially for
      young athletes. Concomitant rotator cuff tendon damage may occur when the
      shoulder dislocates; however, its presence and influence on clinical results have
      not been well described in this patient category. Hypothesis: In opposition to
      current opinion, a substantial number of articular-sided partial-thickness
      rotator cuff tears (APTRCTs) would be found at surgery after a first-time
      traumatic anterior shoulder dislocation in young athletes. However, the impact of
      these injuries on 2-year postoperative results would be negligible. Study Design:
      Cohort study; Level of evidence, 3. Methods: Sixteen male patients (mean age, 21
      years [range, 16-25 years]) with a first-time traumatic anterior shoulder
      dislocation without bony Bankart lesions were included in this study. The
      indications for surgical treatment were age less than 25 years and being active
      in collision or contact sports at a competitive level. Arthroscopic surgery was
      performed at a mean 7.8 days (range, 2-14 days) after injury. Rowe and American
      Shoulder and Elbow Surgeons (ASES) scores as well as range of motion were
      evaluated at a minimum 2 years after an arthroscopic Bankart procedure, and a
      comparison of the clinical results between patients with and without APTRCTs was
      conducted. Results: An anterior-inferior capsulolabral injury was found in all
      patients. There were no bony Bankart lesions. An APTRCT was found in 9 of the 16
      patients. At 2 years after surgical treatment, there were no significant
      differences between the patients with and without APTRCTs in terms of the Rowe
      score (90.0 and 87.1, respectively; P = .69) and ASES score (94.6 and 90.4,
      respectively; P = .67). Conclusion: APTRCTs were found in the superior part of
      the shoulder joint after a first-time traumatic anterior shoulder dislocation in
      a majority of young male athletes treated with surgical stabilization. There were
      no significant differences found between patients with and without APTRCTs in
      terms of the Rowe and ASES scores at 2 years after surgical treatment.

PMID- 30090832
TI  - Propagation of Syndesmotic Injuries During Forced External Rotation in Flexed
      Cadaveric Ankles.
AB  - Background: Forced external rotation of the foot is a mechanism of ankle
      injuries. Clinical observations include combinations of ligament and osseous
      injuries, with unclear links between causation and injury patterns. By observing
      the propagation sequence of ankle injuries during controlled experiments, insight
      necessary to understand risk factors and potential mitigation measures may be
      gained. Hypothesis: Ankle flexion will alter the propagation sequence of ankle
      injuries during forced external rotation of the foot. Study Design: Controlled
      laboratory study. Methods: Matched-pair lower limbs from 9 male cadaveric
      specimens (mean age, 47.0 +/- 11.3 years; mean height, 178.1 +/- 5.9 cm; mean
      weight, 94.4 +/- 30.9 kg) were disarticulated at the knee. Specimens were mounted
      in a test device with the proximal tibia fixed, the fibula unconstrained, and
      foot translation permitted. After adjusting the initial ankle position (neutral,
      n = 9; dorsiflexed, n = 4; plantar flexed, n = 4) and applying a compressive
      preload to the tibia, external rotation was applied by rotating the tibia
      internally while either lubricated anteromedial and posterolateral plates or
      calcaneal fixation constrained foot rotation. The timing of osteoligamentous
      injuries was determined from acoustic sensors, strain gauges, force/moment
      readings, and 3-dimensional bony kinematics. Posttest necropsies were performed
      to document injury patterns. Results: A syndesmotic injury was observed in 5 of 9
      (56%) specimens tested in a neutral initial posture, in 100% of the dorsiflexed
      specimens, and in none of the plantar flexed specimens. Superficial deltoid
      injuries were observed in all test modes. Conclusion: Plantar flexion decreased
      and dorsiflexion increased the incidence of syndesmotic injuries compared with
      neutral matched-pair ankles. Injury propagation was not identical in all ankles
      that sustained a syndesmotic injury, but a characteristic sequence initiated with
      injuries to the medial ligaments, particularly the superficial deltoid, followed
      by the propagation of injuries to either the syndesmotic or lateral ligaments
      (depending on ankle flexion), and finally to the interosseous membrane or the
      fibula. Clinical Relevance: Superficial deltoid injuries may occur in any case of
      hyper-external rotation of the foot. A syndesmotic ankle injury is often
      concomitant with a superficial deltoid injury; however, based on the research
      detailed herein, a deep deltoid injury is then concomitant with a syndesmotic
      injury or offloads the syndesmosis altogether. A syndesmotic ankle injury more
      often occurs when external rotation is applied to a neutral or dorsiflexed ankle.
      Plantar flexion may shift the injury to other ankle ligaments, specifically
      lateral ligaments.

PMID- 30090833
TI  - Age- and Sex-Specific Morphologic Variations of Capital Femoral Epiphysis Growth
      in Children and Adolescents Without Hip Disorders.
AB  - Background: Understanding the development of the capital femoral epiphysis is
      essential to identify pathologic variations that may lead to cam morphology.
      Purpose/Hypothesis: The purpose of this study was to investigate the development
      of the capital femoral epiphysis during childhood and adolescence, with specific
      morphologic analysis of the peripheral growth and the metaphyseal surface of the
      growth plate. We hypothesized that age- and sex-dependent morphologic variations
      of the peripheral growth (cupping) and surface anatomy (epiphyseal tubercle) of
      the epiphysis would be evident with increasing age. Study Design: Cross-sectional
      study; Level of evidence, 3. Methods: Pelvic computed tomography scans of 80
      children and adolescents (range, 8-15 years; n = 10 per age group; 50% male),
      imaged because of suspected appendicitis, were used to reformat the proximal
      femur. All patients had asymptomatic hips with no signs or history of hip
      disorder. We measured the peripheral cupping of the epiphysis and the epiphyseal
      tubercle dimensions from 3-dimensional models. All measurements were normalized
      to the epiphyseal diameter. The effect of age on these parameters was evaluated
      by use of linear regression analysis. A 2-way analysis of variance (ANOVA) was
      used to compare these parameters between males and females. Results: The mean
      epiphyseal cupping increased with increasing age (R2 = 0.54; P < .001). The mean
      normalized epiphyseal cupping was consistently higher in the anterior and
      posterior directions compared with the inferior and superior locations. Male
      patients aged 10 and 11 years had lower (P = .002) mean epiphyseal cupping
      compared with female patients of the same age. We observed no difference between
      male and female participants after 12 years of age (P > .3). The normalized
      epiphyseal tubercle height (R2 = 0.08; P = .009), width (R2 = 0.13; P = .001),
      and length (R2 = 0.45; P < .001) decreased with increasing age, with no
      differences between male and female patients. On average, a 2.6-fold increase was
      found in epiphyseal cupping from 8 to 15 years of age, whereas normalized
      tubercle height decreased by 0.4-fold. Conclusion: Peripheral cupping of the
      epiphysis over the metaphysis increases with age, while the relative epiphyseal
      tubercle dimensions decrease. Females have an earlier onset of rapid increase in
      the peripheral cupping compared with males; however, no differences in epiphyseal
      tubercle dimensions were found between male and female patients. These findings
      may guide future studies investigating the development of cam morphology, which
      should consider the surface morphologic characteristics of the capital femoral
      epiphysis, the growth plate, and the differences in morphologic characteristics
      according to age and sex.

PMID- 30090834
TI  - Establishing Minimal Important Differences for the VR-12 and SANE Scores in
      Patients Following Treatment of Rotator Cuff Tears.
AB  - Background: Minimal important differences (MIDs) for the Veterans RAND 12-Item
      Health Survey (VR-12) and the Single Assessment Numeric Evaluation (SANE) have
      not been reported in patients following treatment for rotator cuff tears (RCTs).
      Purpose: To determine the MIDs for the VR-12 and SANE among patients with RCT
      after treatment. Study Design: Cohort study (diagnosis); Level of evidence, 2.
      Method: A total of 222 patients diagnosed with RCT completed the VR-12 and SANE
      at baseline and then received surgical or nonsurgical treatment. After 64 weeks,
      160 patients completed the VR-12, the SANE, and a global change questionnaire. We
      applied a distribution-based approach to estimate the MIDs for the SANE and for
      the physical component score (PCS) and mental component score (MCS) of the VR-12.
      We then used the global rating score as an anchor for 20 patients who perceived a
      minimal improvement, and we applied an anchor-based approach. One-half standard
      deviation of the baseline score was used in the distribution-based approach.
      Linear regression analyses and backward model selection were conducted to
      evaluate the associations between patients' characteristics and the anchor-based
      MIDs. Results: The MIDs derived from distribution-based method estimates for the
      VR-12 PCS, MCS, and SANE scores were 4.94, 5.99, and 11.80, respectively. The
      MIDs estimated using the anchor-based method for the PCS, MCS, and SANE scores
      were 2.57 (90% CI, -1.62 to 6.76), 1.87 (90% CI, -2.07 to 5.80), and 27.25 (90%
      CI, 16.17 to 38.33), respectively. The final regression model for significant
      predictors of the MID on the PCS included baseline PCS (P < .001), body mass
      index (P = .014), symptom duration (P = .011), diabetes (P = .009), and surgery
      (P = .089). The final model for the MID on the MCS included baseline MCS (P <
      .001), patient sex (P = .027), and diabetes (P = .083). The final model for the
      MID on SANE included baseline SANE score (P = .059) and diabetes (P = .050).
      Conclusion: This is the first study to assess the MIDs for the VR-12 and SANE
      scores in patients with rotator cuff disease. The estimates of MID will
      facilitate the interpretation and application of these outcome measures in
      clinical practice and research.

PMID- 30090835
TI  - Comparison of a Distal Tibial Allograft and Scapular Spinal Autograft for
      Posterior Shoulder Instability With Glenoid Bone Loss.
AB  - Background: Posterior glenoid bone deficiency can occur with recurrent
      glenohumeral instability. Glenoid reconstruction with a distal tibial allograft
      (DTA) has been reported to successfully restore contact pressures that occur
      during posterior glenohumeral translation. However, there are concerns regarding
      the risk of allograft resorption, availability, and costs. Extracapsular
      reconstruction using a scapular spinal autograft (SSA) has been reported as an
      alternative technique secondary to its anatomic location relative to the
      posterior shoulder and preferable autograft properties. There are no known prior
      biomechanical studies evaluating the scapular spine as an effective extracapsular
      graft choice. Purpose: To compare the efficacy of a DTA and SSA in restoring the
      stability of a glenoid with a large posterior bone defect compared with the
      intact native glenoid. Study Design: Controlled laboratory study. Methods: Ten
      cadaveric shoulders were tested. With the use of a custom KUKA robot, a 50-N
      compressive force was applied to the glenohumeral joint. The peak force required
      to translate the humeral head beyond the glenoid lip posteriorly as well as the
      lateral displacement that occurred during posterior translation were measured.
      Testing was performed in 5 conditions: (1) intact glenoid and labrum, (2)
      simulated reverse Bankart lesion, (3) 12-mm posterior glenoid defect, (4) glenoid
      defect reconstructed with a fresh DTA, and (5) glenoid defect reconstructed with
      an SSA. Results: The mean glenoid width was 30 mm. The mean peak force and
      lateral displacement decreased significantly with a glenoid defect (0.99 +/- 2.3
      N and 0.06 +/- 0.09 mm, respectively; P < .0001) compared with the intact glenoid
      (23.00 +/- 9.7 N and 1.83 +/- 0.70 mm, respectively; P = .0001). There was no
      significant difference between the peak force after reconstruction of the defect
      with a DTA (23.00 +/- 7.4 N) and SSA (23.00 +/- 7.7 N) when compared with the
      intact glenoid (P = .9999). There were no significant differences in the peak
      force between the 2 grafts (P = .9999). Additionally, both the DTA (1.04 +/- 1.09
      mm) and the SSA (1.02 +/- 1.17 mm) demonstrated no differences in lateral
      displacement when compared with the intact glenoid (P = .2336 and .2043,
      respectively). There was no difference in lateral displacement that occurred
      between the DTA and SSA (P = .9999). Conclusion: Reconstruction of a large
      posterior glenoid defect with either a DTA or an SSA can effectively restore
      glenohumeral stability. Clinical Relevance: This study supports the use of a DTA
      or SSA in posterior glenoid defect reconstruction. Clinical studies are needed to
      determine the long-term effects of utilizing such grafts.

PMID- 30090836
TI  - The Learning Curve for the Latarjet Procedure: A Systematic Review.
AB  - Background: Anterior shoulder instability, including recurrent instability, is a
      common problem, particularly in young, active patients and contact athletes. The
      Latarjet procedure is a common procedure to treat recurrent shoulder instability.
      Purpose: To identify the reported learning curves associated with the Latarjet
      procedure and to determine a point on the learning curve after which a surgeon
      can be considered to have achieved proficiency. Study Design: Systematic review;
      Level of evidence, 4. Methods: Three online databases (Embase, MEDLINE, PubMed)
      were systematically searched and screened in duplicate by 2 independent
      reviewers. The search included results from the inception of each database to
      January 23, 2017. Data regarding study characteristics, patient demographics,
      learning curve analyses, and complications were collected. Study quality was
      assessed in duplicate. Results: Two level 3 studies and 3 level 4 studies of fair
      methodological quality were included. Overall, 349 patients (350 shoulders) with
      a mean age of 25.1 years (range, 14-52 years) were included in the final data
      analysis. Patients were predominantly male (93.7%). After 22 open and 20 to 40
      arthroscopic Latarjet procedures, surgeons achieved a level of proficiency as
      measured by decreased operative time. For open procedures, complication rates and
      lengths of hospital stay decreased significantly with increased experience
      (Spearman rho = -0.3, P = .009 and Spearman rho = -0.6, P < .0001, respectively).
      Conclusion: With experience, surgeons achieved a level of proficiency in
      performing arthroscopic and open Latarjet procedures, as measured by decreased
      operative time, length of hospital stay, and complication rate. The most commonly
      reported difference was operative time, which was significant across all studies.
      Overall, the Latarjet procedure is a safe procedure with low complication rates,
      although further research is required to truly characterize this learning curve.

PMID- 30090837
TI  - Impact of a Multidisciplinary Infection Prevention Initiative on Central Line and
      Urinary Catheter Utilization in a Long-term Acute Care Hospital.
AB  - Background: Prolonged central line (CL) and urinary catheter (UC) use can
      increase risk of central line-associated bloodstream infection (CLABSI) and
      catheter-associated urinary tract infection (CAUTI). Methods: This interventional
      study conducted in a 76-bed long-term acute care hospital (LTACH) in Southeast
      Michigan was divided into 3 periods: pre-intervention (January 2015-June 2015),
      intervention (July-November 2015), and postintervention (December 2015-March
      2017). During the intervention period, a multidisciplinary infection prevention
      team (MIPT) made weekly recommendations to remove unnecessary CL/UC or switch to
      alternate urinary/intravenous access. Device utilization ratios (DURs) and
      infection rates were compared between the study periods. Interrupted time series
      (ITS) and 0-inflated poisson (ZIP) regression were used to analyze DUR and
      CLABSI/CAUTI data, respectively. Results: UC-DUR was 31% in the pre- and
      postintervention periods and 21% in the intervention period. CL-DUR decreased
      from 46% (pre-intervention) to 39% (intervention) to 37% (postintervention). The
      results of ITS analysis indicated nonsignificant decrease and increase in
      level/trend in DURs coinciding with our intervention. The CAUTI rate per catheter
      days did not decrease during intervention (4.36) compared with pre- (2.49) and
      postintervention (1.93). The CLABSI rate per catheter-days decreased by 73%
      during intervention (0.39) compared with pre-intervention (1.45). Rates again
      quadrupled postintervention (1.58). ZIP analysis indicated a beneficial effect of
      intervention on infection rates without reaching statistical significance.
      Conclusions: We demonstrated that a workable MIPT initiative focusing on removal
      of unnecessary CL and UC can be easily implemented in an LTACH requiring minimal
      time and resources. A rebound increase in UC-DURs to pre-intervention levels
      after intervention end indicates that continued vigilance is required to maintain
      performance.

PMID- 30090838
TI  - Clinical Outcomes Associated With Linezolid Resistance in Leukemia Patients With
      Linezolid-Resistant Staphylococcus epidermidis Bacteremia.
AB  - Background: Coagulase-negative staphylococci, including Staphylococcus
      epidermidis, are the most common cause of bloodstream infection in cancer
      patients. Linezolid resistance is increasingly identified in S. epidermidis, but
      whether such resistance alters the clinical course of S. epidermidis infections
      is unknown. The purpose of this study was to assess the clinical impact of
      linezolid resistance in leukemia patients with S. epidermidis bloodstream
      infection. Methods: This was a retrospective, single-center cohort study of all
      adult leukemia patients with S. epidermidis bacteremia treated with empiric
      linezolid between 2012 and 2015. The primary end point was adverse clinical
      outcome on day 3, defined as a composite of persistent bacteremia, fever,
      intensive care unit admission, or death. Fourteen- and 30-day mortality were also
      assessed. Results: Eighty-two unique leukemia patients with S. epidermidis were
      identified. Linezolid resistance was identified in 33/82 (40%). Patients with
      linezolid-resistant S. epidermidis were significantly more likely to have
      persistent bacteremia (41% vs 7%; adjusted relative risk [aRR], 5.15; 95%
      confidence interval [CI], 1.63-16.30; P = .005); however, adverse short-term
      clinical outcomes overall were not more common among patients with linezolid
      resistant S. epidermidis (61% vs 33%; aRR, 1.46; 95% CI, 0.92-2.32; P = .108). No
      differences were observed in 14- or 30-day mortality. Conclusions: Leukemia
      patients with linezolid-resistant S. epidermidis bacteremia who were treated with
      linezolid were significantly more likely to have persistent bacteremia compared
      with those with linezolid-sensitive isolates. Interventions to limit the clinical
      impact of linezolid-resistant S. epidermidis are warranted.

PMID- 30090839
TI  - Ibrutinib Therapy and Mycobacterium chelonae Skin and Soft Tissue Infection.
AB  - Ibrutinib is an irreversible inhibitor of Bruton's tyrosine kinase approved for
      the treatment of B-cell malignancies. There is growing concern about the risk of
      opportunistic infections following ibrutinib therapy. Herein, we describe the
      first case of Mycobacterium chelonae skin and soft tissue infection in a patient
      receiving ibrutinib and recount the challenges in treating this infection.

PMID- 30090840
TI  - Predictors of Missed Hepatitis C Intake Appointments and Failure to Establish
      Hepatitis C Care Among Patients Living With HIV.
AB  - Background: We estimated and characterized the proportion of patients living with
      HIV (PLWH) who missed hepatitis C (HCV) intake appointments and subsequently
      failed to establish HCV care. Methods: Logistic regression analyses were used to
      identify factors associated with missed HCV intake appointments and failure to
      establish HCV care among PLWH referred for HCV treatment between January 2014 and
      December 2017. In addition to demographics, variables included HIV treatment
      characteristics, type of insurance, liver health status, active alcohol or
      illicit drug use, unstable housing, and history of a mental health disorder
      (MHD). Results: During the study period, 349 new HCV clinic appointments were
      scheduled for 202 unduplicated patients. Approximately half were nonwhite, and
      80% had an undetectable HIV viral load. Drug use (31.7%), heavy alcohol use
      (32.8%), and MHD (37.8%) were prevalent. Over the 4-year period, 21.9% of PLWH
      referred for HCV treatment missed their HCV intake appointment. The proportion
      increased each year, from 17.2% in 2014 to 25.4% in 2017 (P = .021). Sixty-six of
      the 202 newly referred HCV patients (32.7%) missed their first HCV appointment,
      and 28 of these (42.4%) failed to establish HCV care. Having a history of MHD,
      CD4 <200, ongoing drug use, and being nonwhite were independent predictors of
      missing an intake HCV appointment. The strongest predictor of failure to
      establish HCV care was having a detectable HIV viral load. Conclusions: The
      proportion of PLWH with missed HCV appointments increased over time. HCV
      elimination among PLWH may require integrated treatment of MHD and substance use.

PMID- 30090841
TI  - Worster-Drought Syndrome Associated With LINS Mutations.
AB  - Worster-Drought syndrome is a congenital, pseudobulbar paresis. There is no
      identified molecular etiology despite familial cases reported. The authors report
      a boy who was diagnosed with Worster-Drought syndrome due to longstanding
      drooling, dysphagia, and impaired tongue movement. Magnetic resonance imaging of
      the brain was unrevealing. At 14 years old, he remains aphonic with normal facial
      and extraocular movements. Nonsense mutations in the LINS gene, p.Glu366X and
      p.Lys393X, were found. Results from neuropsychological testing at 14 years old
      were consistent with a diagnosis of intellectual disability and revealed
      nonverbal reasoning skills at a 5-year-old level with relative sparing of his
      receptive vocabulary and visual attention. Compared to prior testing at 9 years
      old, his receptive language improved from a 6-year-old to an 8.5-year-old level.
      The authors report LINS mutations associated with Worster-Drought syndrome. This
      highlights that despite severe and persistent aphonia, receptive language
      improvements can be observed within the context of intellectual disability.

PMID- 30090842
TI  - Cerebrospinal Fluid-Directed rAAV9-rsATP7A Plus Subcutaneous Copper Histidinate
      Advance Survival and Outcomes in a Menkes Disease Mouse Model.
AB  - Menkes disease is a lethal neurodegenerative disorder of copper metabolism caused
      by mutations in an evolutionarily conserved copper transporter, ATP7A. Based on
      our prior clinical and animal studies, we seek to develop a therapeutic approach
      suitable for application in affected human subjects, using the mottled-brindled
      (mo-br) mouse model that closely mimics the Menkes disease biochemical and
      clinical phenotypes. Here, we evaluate the efficacy of low-, intermediate-, and
      high-dose recombinant adeno-associated virus serotype 9 (rAAV9)-ATP7A delivered
      to the cerebrospinal fluid (CSF), in combination with subcutaneous administration
      of clinical-grade copper histidinate (sc CuHis, IND #34,166). Mutant mice that
      received high-dose (1.6 * 1010 vg) cerebrospinal fluid-directed rAAV9-rsATP7A
      plus sc copper histidinate showed 53.3% long-term (>=300-day) survival compared
      to 0% without treatment or with either treatment alone. The high-dose rAAV9
      rsATP7A plus sc copper histidinate-treated mutant mice showed increased brain
      copper levels, normalized brain neurochemical levels, improvement of brain
      mitochondrial abnormalities, and normal growth and neurobehavioral outcomes. This
      synergistic treatment effect represents the most successful rescue to date of the
      mo-br mouse model. Based on these findings, and the absence of a large animal
      model, we propose cerebrospinal fluid-directed rAAV9-rsATP7A gene therapy plus
      subcutaneous copper histidinate as a potential therapeutic approach to cure or
      ameliorate Menkes disease.

PMID- 30090843
TI  - Remission of Gilles de la Tourette Syndrome after Heat-Induced Dehydration.
AB  - Heat has been reported to exert variable effects on people with Gilles de la
      Tourette syndrome (TS). At age 24 years, a 32-year-old right-handed man with TS
      experienced a marked reduction in tics for two years after undergoing dehydration
      by entering a hot tub at 103 degrees F (39.4 degrees C) to 104 degrees F (40.0
      degrees C) for 3 to 4 hours. On the Yale Global Tic Severity Scale (YGTSS) he
      scored 55 seven months before dehydration and 13 one month after dehydration. An
      intense heat exposure and dehydration led to an apparent remission in tics. The
      remission continued without the use of prescribed or nonprescribed medications or
      substances for two years until tics returned in the worst ever exacerbation after
      a tetanus immunization. The heat exposure may have altered at least temporarily
      his thermostat for normal heat-loss mechanisms through dopaminergic pathways from
      the anterior hypothalamus to the basal ganglia and the substantia nigra. Whether
      or not that mechanism or some other mechanism relevant to the heat exposure
      and/or dehydration is at play, the sudden and marked improvement in his tics
      needs further attention. Prospective testing of the heat and dehydration effect
      on tics should be pursued.

PMID- 30090844
TI  - Possible role of nicotine and cotinine on nitroxidative stress and antioxidant
      content in saliva of smokeless tobacco consumers.
AB  - The aim of the study is to levels of nicotine and cotinine were elevated the
      oxidative stress malondialdehyde (MDA) and inflammation as nitric oxide (NO2 and
      NO3) may possibly be associated with decreased antioxidant enzyme activities and
      can sensitively indicate the production of reactive oxygen species (ROS). To
      evaluate the quantitative analysis of nicotine and cotinine levels and the
      alterations in the selected parameters of antioxidant metabolisms during
      nitroxidative stress in the saliva of smokeless tobacco consumers. Saliva
      nicotine and cotinine was measured by HPLC method and nitric oxide, lipid
      peroxidation and activities of antioxidant enzymes were estimated by
      spectrophotometric methods. Significant increase in concentrations of nicotine
      and cotinine levels of saliva in smokeless tobacco users in comparison to
      controls. Saliva lipid peroxidation was increased in experimental subjects
      (gutkha group 39.28% and khaini group 25.00%) as compared to controls and nitric
      oxide in the form of nitrites and nitrates was significantly increased in the
      saliva of smokeless tobacco users compared to controls. The activity levels of
      antioxidant enzymes were decreased in the saliva of the smokeless tobacco users
      in comparison with normal controls. A strong positive correlation of nicotine and
      cotinine with nitroxidative stress markers in gutkha and khaini users. Increased
      expression of inducible nitric oxide synthase (iNOS) enzyme leads to intoxication
      in saliva and indirectly induces inflammation process. Increased production of
      reactive oxygen species (ROS) and decrease in the activity levels of antioxidant
      enzymes in the saliva of smokeless tobacco users indicate conspicuous cell and
      tissue damage.

PMID- 30090845
TI  - Coherent fluctuation nephelometry as a promising method for diagnosis of
      bacteriuria.
AB  - Objectives: Specialized analyzers are used to automate the diagnosis of
      bacteriuria in laboratory practice. They are based on analysis of microorganisms
      concentration in urine samples or recording the growth of urine microflora.
      Coherent fluctuation nephelometry (CFN) has high sensitivity and allows analyzing
      both parameters simultaneously. The aim of the study is to compare the
      effectiveness of CFN-based and flow cytometry based analyzers. Design and
      methods: Total 117 urine samples from children were studied in parallel using the
      CFN-analyzer and UF-1000i (Sysmex), the results were confirmed by conventional
      microbiological methods. Results: In 21 urine samples (18%), significant
      bacteriuria was determined (>=104 CFU/ml). The best diagnostic indicators were
      obtained while testing urine samples using the CFN-analyzer. The most efficient
      bacteriuria diagnosis is achieved by simultaneous analyses of microorganisms
      concentration in urine and growth of urine microflora (sensitivity - 95.2%,
      specificity - 96.9%, positive predictive value - 87%, negative predictive value -
      98.9%, diagnostic odds ratio - 81.7, positive likelihood ratio - 30.5, negative
      likelihood ratio- 0.049, area under curve in ROC-analysis - 0.987). The CFN
      analyzer allows the preliminary selection of negative urine samples, which do not
      require further analysis by conventional microbiological methods, thereby
      decreasing the number of cultures by 80.3%. Conclusions: This study suggests that
      the CFN-analyzer is the effective tool for bacteriuria screening in children.

PMID- 30090846
TI  - Objectively measured physical activity profile and cognition in Finnish elderly
      twins.
AB  - Introduction: We studied whether objectively measured physical activity (PA) and
      sedentary behavior (SB) are associated with cognition in Finnish elderly twins.
      Methods: This cross-sectional study comprised twins born in Finland from 1940 to
      1944 in the Older Finnish Twin Cohort (mean age, 72.9 years; 726 persons). From
      2014 to 2016, cognition was assessed with a validated telephonic interview,
      whereas PA was measured with a waist-worn accelerometer. Results: In between
      family models, SB and light physical activity had significant linear associations
      with cognition after adjusting for age, sex, wearing time, education level, body
      mass index, and living condition (SB: beta-estimate, -0.21 [95% confidence
      intervals, -0.42 to -0.003]; light physical activity: beta-estimate, 0.30 [95%
      confidence intervals, 0.02-0.58]). In within-family models, there were no
      significant linear associations between objectively measured PA and cognition.
      Discussion: Objectively measured light physical activity and SB are associated
      with cognition in Finnish twins in their seventies, but the associations were
      attributable to genetic and environmental selection.

PMID- 30090847
TI  - Caregiving, intellectual disability, and dementia: Report of the Summit Workgroup
      on Caregiving and Intellectual and Developmental Disabilities.
AB  - Introduction: A specially commissioned working group produced a report on
      caregiving, intellectual and developmental disabilities (IDDs), and dementia for
      the National Institutes of Health-located National Research Summit on Care,
      Services, and Supports for Persons with Dementia and Their Caregivers. Methods:
      Experts in caregiving, dementia, and IDDs examined the current state of research,
      policy, and practice related to caregiving and supports; identified the
      similarities and dissimilarities between IDD-related care and services and the
      general population affected by dementia; and considered how these findings might
      contribute to the conversation on developing a dementia care research and
      services development agenda. Results: Five major areas related to programs and
      caregiving were assessed: (1) challenges of dementia; (2) family caregiving
      interventions; (3) supportive care settings; (4) effects of diversity; and (5)
      bridging service networks of aging and disability. Discussion: Recommendations
      included increasing supports for caregivers of adults with IDDs and dementia;
      increasing research on community living settings and including caregivers of
      persons with IDDs in dementia research; acknowledging cultural values and
      practice diversity in caregiving; increasing screening for dementia and raising
      awareness; and leveraging integration of aging and disability networks.

PMID- 30090848
TI  - Adherence/Retention Alzheimer's Prevention Initiative Colombia Plan.
AB  - Introduction: The Alzheimer's Prevention Initiative Colombia Trial is a
      collaborative project involving the Neurosciences Group of Antioquia,
      Genentech/Roche, and the Banner Alzheimer's Institute, studying whether
      crenezumab can delay or prevent the clinical onset of Alzheimer's disease in
      cognitively unimpaired individuals who carry the PSEN1 E280A mutation. In an
      effort to optimize participant compliance and adherence and maintain interest in
      the trial for its duration, the Neurosciences Group of Antioquia developed an
      "Adherence/Retention Plan." This plan identifies potential barriers to trial
      adherence related to characteristics of the participants and study partners,
      protocol design, sponsors, investigators, environmental factors, and
      characteristics of this population in general and identifies potential solutions
      to these barriers. Methods: Neurosciences Group of Antioquia designed and
      implemented a number of strategies including a) a prescreening process that
      emphasized detailed and staged informed consent involving the participant and
      family and/or friends, b) a schedule of visits and assessments designed to
      minimize burden while achieving the trial's aims, c) appointment reminders, d)
      reimbursement for transportation and missed work, e) meals during study visits,
      f) birthday cards, g) quarterly newsletters, h) annual in-person feedback
      meetings, i) a supplemental health plan to participants, and j) a social plan to
      support family members. All the methods used in this plan were approved by local
      ethics committees. Results: By the end of the fourth year of the trial,
      participant retention was 94.0%, with most participants reporting that they felt
      "very satisfied" with their participation in the trial. Discussion: The
      Adherence/Retention Plan plays a crucial role in maintaining adherence and
      compliance needed to achieve the ambitious goals of the Alzheimer's Prevention
      Initiative-Colombia Autosomal Dominant Alzheimer's Disease Trial and may offer
      guideposts for other prevention trials.

PMID- 30090849
TI  - Case-finding in clinical practice: An appropriate strategy for dementia
      identification?
AB  - Earlier diagnosis of dementia is increasingly being recognized as a public health
      priority. As screening is not generally recommended, case-finding in clinical
      practice is encouraged as an alternative dementia identification strategy. The
      approaches of screening and case-finding are often confused, with uncertainty
      about what case-finding should involve and under what circumstances it is
      appropriate. We propose a formal definition of dementia case-finding with a clear
      distinction from screening. We critically examine case-finding policy and
      practice and propose evidence requirements for implementation in clinical
      practice. Finally, we present a case-finding pathway and discuss the available
      evidence for best practice at each stage, with recommendations for research and
      practice. In conclusion, dementia case-finding is a promising strategy but
      currently not appropriate due to the substantial gaps in the evidence base for
      several components of this approach.

PMID- 30090850
TI  - Patient perspectives of the experience of a computerized cognitive assessment in
      a clinical setting.
AB  - Introduction: Computerized assessments are becoming widely accepted in the
      clinical setting and as a potential outcome measure in clinical trials. To gain
      patient perspectives of this experience, the aim of the present study was to
      investigate patient attitudes and perceptions of the Cognigram [Cogstate], a
      computerized cognitive assessment. Methods: Semi-structured interviews were
      conducted with 19 older adults undergoing a computerized cognitive assessment at
      the University of British Columbia Hospital Clinic for Alzheimer Disease and
      Related Disorders. Thematic analysis was applied to identify key themes and
      relationships within the data. Results: The analysis resulted in three
      categories: attitudes toward computers in healthcare, the cognitive assessment
      process, and evaluation of the computerized assessment experience. The results
      show shared views on the need for balance between human and computer
      intervention, as well as room for improvement in test design and utility.
      Discussion: Careful design and user-testing should be made a priority in the
      development of computerized assessment interfaces, as well as reevaluating the
      cognitive assessment process to minimize patient anxiety and discomfort. Future
      research should move toward continuous data capture within clinical trials and
      ensuring instruments of high reliability to reduce variance.

PMID- 30090851
TI  - 3D-Printing of Functional Biomedical Microdevices via Light- and Extrusion-Based
      Approaches.
AB  - 3D-printing is a powerful additive manufacturing tool, one that enables
      fabrication of biomedical devices and systems that would otherwise be challenging
      to create with more traditional methods such as machining or molding. Many
      different classes of 3D-printing technologies exist, most notably extrusion-based
      and light-based 3D-printers, which are popular in consumer markets, with
      advantages and limitations for each modality. The focus here is primarily on
      showcasing the ability of these 3D-printing platforms to create different types
      of functional biomedical microdevices-their advantages and limitations are
      covered with respect to other classes of 3D-printing, as well as the past,
      recent, and future efforts to advance the functional microdevice domain. In
      particular, the fabrication of micromachines/robotics, drug-delivery devices,
      biosensors, and microfluidics is addressed. The current challenges associated
      with 3D-printing of functional microdevices are also addressed, as well as future
      directions to improve both the printing techniques and the performance of the
      printed products.

PMID- 30090852
TI  - Characterization of Tissue Plasminogen Activator Expression and Trafficking in
      the Adult Murine Brain.
AB  - Tissue plasminogen activator (tPA) is an immediate-early gene important for
      regulating physiological processes like synaptic plasticity and neurovascular
      coupling. It has also been implicated in several pathological processes including
      blood-brain barrier (BBB) permeability, seizure progression, and stroke. These
      varied reports suggest that tPA is a pleiotropic mediator whose actions are
      highly compartmentalized in space and time. The specific localization of tPA,
      therefore, can provide useful information about its function. Accordingly, the
      goal of this study was to provide a detailed characterization of tPA's regional,
      cellular, and subcellular localization in the brain. To achieve this, two new
      transgenic mouse lines were utilized: (1) a PlatbetaGAL reporter mouse, which
      houses the beta-galactosidase gene in the tPA locus and (2) a tPABAC-Cerulean
      mouse, which has a cerulean-fluorescent protein fused in-frame to the tPA C
      terminus. Using these two transgenic reporters, we show that while tPA is
      expressed throughout most regions of the adult murine brain, it appears to be
      preferentially targeted to fiber tracts in the limbic system. In the hippocampus,
      confocal microscopy revealed tPA-Cerulean (tPA-Cer) puncta localized to giant
      mossy fiber boutons (MFBs) and astrocytes in stratum lucidum. With amplification
      of the tPA-Cer signal, somatically localized tPA was also observed in the stratum
      oriens (SO)/alveus layer of both CA1 and CA3 subfields. Coimmunostaining of tPA
      Cer and interneuronal markers indicates that these tPA-positive cell bodies
      belong to a subclass of somatostatin (SST)/oriens-lacunosum moleculare (O-LM)
      interneurons. Together, these data imply that tPA's localization is
      differentially regulated, suggesting that its neuromodulatory effects may be
      compartmentalized and specialized to cell type.

PMID- 30090853
TI  - Novel pathological features and potential therapeutic approaches for CADASIL:
      insights obtained from a mouse model of CADASIL.
AB  - Cerebral autosomal dominant arteriopathy with subcortical infarcts and
      leukoencephalopathy (CADASIL) is the most common condition of hereditary stroke
      and vascular dementia. CADASIL is caused by Notch3 mutation, leading to
      progressive degeneration of vascular smooth muscle cells (vSMCs) of the small
      arteries in the brain. However, the pathogenesis of CADASIL remains largely
      unknown, and treatment that can stop or delay the progression of CADASIL is not
      yet available. Using both wild type mice and transgenic mice carrying the human
      mutant Notch3 gene (CADASIL mice), we have recently characterized the
      pathological features of CADASIL and determined the therapeutic efficacy of two
      hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony
      stimulating factor (G-CSF) in CADASIL. Our findings have revealed novel
      pathological changes in the endothelium of cerebral capillaries and in the neural
      stem cells (NSCs). We have also observed the impairment of cognitive function in
      CADASIL mice. Moreover, SCF+G-CSF treatment improves cognitive function, inhibits
      Notch3 mutation-induced vSMC degeneration, cerebral blood bed reduction, cerebral
      capillary damage, and NSC loss, and increases neurogenesis and angiogenesis. Here
      we compile an overview of our recently published studies, which provide new
      insights into understanding the pathogenesis of CADASIL and developing
      therapeutic strategies for this devastating neurological disease.

PMID- 30090854
TI  - Comparing a Mechanical Analogue With the Da Vinci User Interface: Suturing at
      Challenging Angles.
AB  - The da Vinci Surgical System offers a natural user interface and wrist
      articulation, which enable suturing and other complex surgical actions in
      confined spaces. However, both the one-time cost of the system and the recurring
      cost of the limited-use instruments remain high. This has motivated the
      development of several hand-held alternatives-some partially motorized, some
      fully mechanical-in recent years. While a few of these have been commercialized,
      none have yet met with broad commercial success comparable to the da Vinci robot.
      In this letter, we suggest a user interface-based explanation for this, and
      describe a new mechanical instrument that provides wrist articulation with a
      novel user interface. We provide results of a single-user pilot study with an
      experienced laparoscopic surgeon to compare the new device with a traditional
      wristless laparoscopic tool, a prior commercial wristed mechanical tool (the
      RealHand), and the da Vinci robot, in the context of suturing at challenging
      angles. We observe better targeting of desired suture needle entry and exit
      points with the new device in comparison to prior wristed and wristless
      mechanical instruments, with the da Vinci only slightly outperforming the new
      tool.

PMID- 30090855
TI  - Computational Modeling of Contrast Sensitivity and Orientation Tuning in First
      Episode and Chronic Schizophrenia.
AB  - Computational modeling is a useful method for generating hypotheses about the
      contributions of impaired neurobiological mechanisms, and their interactions, to
      psychopathology. Modeling is being increasingly used to further our understanding
      of schizophrenia, but to date, it has not been applied to questions regarding the
      common perceptual disturbances in the disorder. In this article, we model aspects
      of low-level visual processing and demonstrate how this can lead to testable
      hypotheses about both the nature of visual abnormalities in schizophrenia and the
      relationships between the mechanisms underlying these disturbances and psychotic
      symptoms. Using a model that incorporates retinal, lateral geniculate nucleus
      (LGN), and V1 activity, as well as gain control in the LGN, homeostatic
      adaptation in V1, lateral excitation and inhibition in V1, and self-organization
      of synaptic weights based on Hebbian learning and divisive normalization, we show
      that (a) prior data indicating increased contrast sensitivity for low-spatial
      frequency stimuli in first-episode schizophrenia can be successfully modeled as a
      function of reduced retinal and LGN efferent activity, leading to
      overamplification at the cortical level, and (b) prior data on reduced contrast
      sensitivity and broadened orientation tuning in chronic schizophrenia can be
      successfully modeled by a combination of reduced V1 lateral inhibition and an
      increase in the Hebbian learning rate at V1 synapses for LGN input. These models
      are consistent with many current findings, and they predict several relationships
      that have not yet been demonstrated. They also have implications for
      understanding changes in brain and visual function from the first psychotic
      episode to the chronic stage of illness.

PMID- 30090856
TI  - A Neural Model of Empathic States in Attachment-Based Psychotherapy.
AB  - We build on a neuroanatomical model of how empathic states can motivate
      caregiving behavior, via empathy circuit-driven activation of regions in the
      hypothalamus and amygdala, which in turn stimulate a mesolimbic-ventral pallidum
      pathway, by integrating findings related to the perception of pain in self and
      others. On this basis, we propose a network to capture states of personal
      distress and (weak and strong forms of) empathic concern, which are particularly
      relevant for psychotherapists conducting attachment-based interventions. This
      model is then extended for the case of self-attachment therapy, in which
      conceptualized components of the self serve as both the source of and target for
      empathic resonance. In particular, we consider how states of empathic concern
      involving an other that is perceived as being closely related to the self might
      enhance the motivation for self-directed bonding (which in turn is proposed to
      lead the individual toward more compassionate states) in terms of medial
      prefrontal cortex-mediated activation of these caregiving pathways. We simulate
      our model computationally and discuss the interplay between the bonding and
      empathy protocols of the therapy.

PMID- 30090857
TI  - Can Peripheral Blood-Derived Gene Expressions Characterize Individuals at Ultra
      high Risk for Psychosis?
AB  - The ultra-high risk (UHR) state was originally conceived to identify individuals
      at imminent risk of developing psychosis. Although recent studies have suggested
      that most individuals designated UHR do not, they constitute a distinctive group,
      exhibiting cognitive and functional impairments alongside multiple psychiatric
      morbidities. UHR characterization using molecular markers may improve
      understanding, provide novel insight into pathophysiology, and perhaps improve
      psychosis prediction reliability. Whole-blood gene expressions from 56 UHR
      subjects and 28 healthy controls are checked for existence of a consistent gene
      expression profile (signature) underlying UHR, across a variety of normalization
      and heterogeneity-removal techniques, including simple log-conversion, quantile
      normalization, gene fuzzy scoring (GFS), and surrogate variable analysis. During
      functional analysis, consistent and reproducible identification of important
      genes depends largely on how data are normalized. Normalization techniques that
      address sample heterogeneity are superior. The best performer, the unsupervised
      GFS, produced a strong and concise 12-gene signature, enriched for psychosis
      associated genes. Importantly, when applied on random subsets of data,
      classifiers built with GFS are "meaningful" in the sense that the classifier
      models built using genes selected after other forms of normalization do not
      outperform random ones, but GFS-derived classifiers do. Data normalization can
      present highly disparate interpretations on biological data. Comparative analysis
      has shown that GFS is efficient at preserving signals while eliminating noise.
      Using this, we demonstrate confidently that the UHR designation is well
      correlated with a distinct blood-based gene signature.

PMID- 30090858
TI  - A Theoretical Framework for Evaluating Psychiatric Research Strategies.
AB  - One of the major goals of basic studies in psychiatry is to find etiological
      mechanisms or biomarkers of mental disorders. A standard research strategy to
      pursue this goal is to compare observations of potential factors from patients
      with those from healthy controls. Classifications of individuals into patient and
      control groups are generally based on a diagnostic system, such as the Diagnostic
      and Statistical Manual of Mental Disorders (DSM) or the International
      Classification of Diseases (ICD). Several flaws in these conventional diagnostic
      based approaches have been recognized. The flaws are primarily due to the
      complexity in the relation between the pathogenetic factors (causes) and
      disorders: The current diagnostic categories may not reflect the underlying
      etiological mechanisms. To overcome this difficulty, the National Institute of
      Mental Health initiated a novel research strategy called Research Domain Criteria
      (RDoC), which encourages studies to focus on the neurobiological mechanisms and
      core aspects of behavior rather than to rely on traditional diagnostic
      categories. However, how RDoC can improve research in psychiatry remains a matter
      of debate. In this article, we propose a theoretical framework for evaluating
      psychiatric research strategies, including the conventional diagnostic category
      based approaches and the RDoC approach. The proposed framework is based on the
      statistical modeling of the processes of how the disorder arises from
      pathogenetic factors. This framework provides the statistical power to quantify
      how likely relevant pathogenetic factors are to be detected under various
      research strategies. On the basis of the proposed framework, we can discuss which
      approach performs better in different types of situations. We present several
      theoretical and numerical results that highlight the advantages and disadvantages
      of the strategies. We also demonstrate how a computational model is incorporated
      into the proposed framework as a generative model of behavioral observations.
      This demonstration highlights how the computational models contribute to
      designing psychiatric studies.

PMID- 30090859
TI  - A Bayesian Approach to Modeling Risk of Hospital Admissions Associated With
      Schizophrenia Accounting for Underdiagnosis of the Disorder in Administrative
      Records.
AB  - Schizophrenia is a debilitating serious mental illness characterized by a complex
      array of symptoms with varying severity and duration. Patients may seek treatment
      only intermittently, contributing to challenges diagnosing the disorder. A
      misdiagnosis may potentially bias and reduce study validity. Thus we developed a
      statistical model to assess the risk of 1-year hospitalization for patients
      diagnosed with schizophrenia, accounting for when schizophrenia is underreported
      in administrative databases. A retrospective study design identified patients
      seeking care during 2010 within an integrated health care system from the Health
      Maintenance Organization Research Network located in the southwestern United
      States. Bayesian analysis addressed the problem of underdiagnosed schizophrenia
      with a statistical measurement error model assuming varying rates of
      underreporting. Results were then compared to classical multivariable logistic
      regression. Assuming no underreporting, there was an 87% greater relative odds of
      hospitalization associated with schizophrenia, OR = 1.87, CI [1.08, 3.23]. Effect
      sizes and interval estimates representing the association between hospitalization
      and schizophrenia were reduced with the Bayesian approach accounting for
      underdiagnosis, suggesting that less severe patients may be underrepresented in
      studies of schizophrenia. The analytical approach has useful applications in
      other contexts where the identification of patients with a given condition may be
      underreported in administrative records.

PMID- 30090860
TI  - Mechanisms Underlying Dopamine-Induced Risky Choice in Parkinson's Disease With
      and Without Depression (History).
AB  - Patients with Parkinson's disease (PD) are often treated with dopaminergic
      medication. Dopaminergic medication is known to improve both motor and certain
      nonmotor symptoms, such as depression. However, it can contribute to behavioral
      impairment, for example, by enhancing risky choice. Here we characterize the
      computational mechanisms that contribute to dopamine-induced changes in risky
      choice in PD patients with and without a depression (history). We adopt a
      clinical-neuroeconomic approach to investigate the effects of dopaminergic
      medication on specific components of risky choice in PD. Twenty-three healthy
      controls, 21 PD patients with a depression (history), and 22 nondepressed PD
      patients were assessed using a well-established risky choice paradigm. Patients
      were tested twice: once after taking their normal dopaminergic medication and
      once after withdrawal of their medication. Dopaminergic medication increased a
      value-independent gambling propensity in nondepressed PD patients, while leaving
      loss aversion unaffected. By contrast, dopaminergic medication effects on loss
      aversion were associated with current depression severity and with drug effects
      on depression scores. The present findings demonstrate that dopaminergic
      medication increases a value-independent gambling bias in nondepressed PD
      patients. Moreover, the current study raises the hypothesis that dopamine-induced
      reductions in loss aversion might underlie previously observed comorbidity
      between depression and medication-related side effects in PD, such as impulse
      control disorder.

PMID- 30090861
TI  - Perturbing the Hypothalamic-Pituitary-Adrenal Axis: A Mathematical Model for
      Interpreting PTSD Assessment Tests.
AB  - We use a dynamical systems model of the hypothalamic-pituitary-adrenal (HPA) axis
      to understand the mechanisms underlying clinical protocols used to probe patient
      stress response. Specifically, we address dexamethasone (DEX) and ACTH challenge
      tests, which probe pituitary and adrenal gland responses, respectively. We show
      that some previously observed features and experimental responses can arise from
      a bistable mathematical model containing two steady-states, rather than relying
      on specific and permanent parameter changes due to physiological disruption.
      Moreover, we show that the timing of a perturbation relative to the intrinsic
      oscillation of the HPA axis can affect challenge test responses. Conventional
      mechanistic hypotheses supported and refuted by the challenge tests are
      reexamined by varying parameters in our mathematical model associated with these
      hypotheses. We show that (a) adrenal hyposensitivity can give rise to the
      responses seen in ACTH challenge tests and (b) enhanced cortisol-mediated
      suppression of the pituitary in subjects with PTSD is not necessary to explain
      the responses observed in DEX stress tests. We propose a new two-stage
      DEX/external stressor protocol to more clearly distinguish between the
      conventional hypothesis of enhanced suppression of the pituitary and bistable
      dynamics hypothesized in our model.

PMID- 30090862
TI  - Computation in Psychotherapy, or How Computational Psychiatry Can Aid Learning
      Based Psychological Therapies.
AB  - Learning-based therapies, such as cognitive-behavioral therapy, are used
      worldwide, and their efficacy is endorsed by health and research funding
      agencies. However, the mechanisms behind both their strengths and their
      weaknesses are inadequately understood. Here we describe how advances in
      computational modeling may help formalize and test hypotheses regarding how
      patients make inferences, which are core postulates of these therapies.
      Specifically, we highlight the relevance of computations with regard to the
      development, maintenance, and therapeutic change in psychiatric disorders. A
      Bayesian approach helps delineate which apparent inferential biases and aberrant
      beliefs are in fact near-normative, given patients' current concerns, and which
      are not. As examples, we formalize three hypotheses. First, high-level
      dysfunctional beliefs should be treated as beliefs over models of the world.
      There is a need to test how, and whether, people apply these high-level beliefs
      to guide the formation of lower level beliefs important for real-life decision
      making, conditional on their experiences. Second, during the genesis of a
      disorder, maladaptive beliefs grow because more benign alternative schemas are
      discounted during belief updating. Third, we propose that when patients learn
      within therapy but fail to benefit in real life, this can be accounted for by a
      mechanism that we term overaccommodation, similar to that used to explain fear
      reinstatement. Beyond these specifics, an ambitious collaborative research
      program between computational psychiatry researchers, therapists, and experts-by
      experience needs to form testable predictions out of factors claimed to be
      important for therapy.

PMID- 30090863
TI  - More Shared Responsibility for "More Appropriate Communication".
AB  - The term "more appropriate communication" appears in more than 400 scholarly
      articles (according to Google Scholar). I examined the first 100 scholarly
      articles that pertained to communication between humans (rather than
      communication between computer networks). The question I sought to answer was
      who, according to the scholarly literature, bears responsibility for achieving
      "more appropriate communication?" Of the 100 scholarly articles examined, only a
      slim minority, N=7, imply that "more appropriate communication" is a
      responsibility shared among two or more communication partners, and most of these
      articles address "more appropriate communication" between literal peers, such as
      undergraduate students with other undergraduate students. The majority of
      scholarly articles, N=61, imply that the responsibility for "more appropriate
      communication" lies with the more powerful communication partners (i.e., people
      who have more status, experience, or resources). The remaining third of the
      scholarly articles (N=32) imply that responsibility for "more appropriate
      communication" lies 1with the less powerful communication partners, and these
      less powerful communication partners are frequently children with developmental
      disabilities. I conclude by suggesting that the responsibility for "more
      appropriate communication," particularly with developmentally disabled children,
      either should be assumed by the more powerful communication partners or should be
      shared.

PMID- 30090864
TI  - Simulated Encounters With Vaccine-Hesitant Parents: Arts-Based Video Scenario and
      a Writing Exercise.
AB  - Vaccine hesitancy is an increasing and urgent global public health challenge.
      Medical students' encounters with vaccine-hesitant parents, however, remain
      incidental and unexplored. During pre-clinical training, the vaccine-hesitant
      parents are typically represented through impersonal text-based cases, lists of
      their concerns, and sometimes a virtual patient. However, in reality, vaccine
      hesitant parents have many health beliefs and arguments that are accompanied with
      intense emotions, and students remain unaware and unprepared for them. This study
      is an experimental pilot test in stimulating the medical students' understanding
      of, and ability to respond to, vaccine-hesitant parents' beliefs and questions.
      An arts-based video scenario and a writing exercise are used to demonstrate a
      rich case of vaccine hesitancy, including a simulated dialogue between a parent
      and a student. The study invites vaccine-hesitant parents to ask questions to
      medical students, then it incorporates these questions in a video scenario and
      subsequently invites the students to answer these questions as junior doctors.
      The study examines how the peer group discussion after the video viewing
      resembles a hospital breakroom conversation and how the written dialogue with a
      vaccine-hesitant parent simulates a consultation-room encounter.

PMID- 30090865
TI  - Common Illnesses in Tropical Asia and Significance of Medical Volunteering.
AB  - This study was conducted to provide practical information for actual preparation
      of medical volunteering in tropical Asia, mainly the distribution of common
      illnesses encountered during mission. From 2012 to 2017, we visited two rural
      areas of Eastern Cambodia for medical volunteering missions, Cham Lak and Khsoem.
      Neither area has electricity or public water. We classified the common cases
      encountered during missions into six groups (upper respiratory infection,
      gastroenteritis, vaginitis and/or cystitis, dermatitis, work-related pain and
      parasite prevention) and assessed the distribution. In Cham Lak and Khsoem, 558
      and 371 people were treated, respectively. The most commonly encountered cases in
      children under age of 18 were upper respiratory infection, followed by parasite
      control and dermatitis, in both areas. There was no significant difference in
      distribution between the two areas. For adults, the most common illnesses in Cham
      Lak area were vaginitis and/or cystitis, followed by gastroenteritis and work
      related pain. In Khsoem area, the common illnesses were work-related pain
      followed by gastroenteritis, and upper respiratory infection. The distribution
      between the two areas differed significantly (p <0.001). The difference might be
      due to the water source and main crops of agriculture. Successful preparation of
      a medical volunteering needs deep understanding of the destination community.

PMID- 30090866
TI  - Thin films of binary amorphous Zn-Zr alloys developed by magnetron co-sputtering
      for the production of degradable coronary stents: A preliminary study.
AB  - Image 1.

PMID- 30090867
TI  - Differential Activation of the Left and Right Cerebral Hemispheres of Individuals
      Who Use or are Dependent on Drugs of Abuse.
AB  - Introduction: The left and right cerebral hemispheres are not equivalent in
      performance of cognitive functions associated with risk factors of drug abuse,
      nor is their development equivalently affected by drugs of abuse. The question
      addressed here is whether drugs of abuse affect cognitive function as assessed by
      brain activation, in particular related to impulsivity, and/or whether weaker
      brain activation associated with impulsivity increases the risk of drug abuse.
      Methodology: Using PubMed and key words, articles were selected that addressed
      brain activation in individuals who used or abused one of the psychoactive drugs.
      Findings are summarized. Results: For each of the drugs, hypoactivation was
      found. In some cases this reduced activation was reported predominantly for the
      right or both hemispheres. There were fewer reports for the left hemisphere.
      Discussion and Conclusion: Rarely do authors focus on why only one or the other
      hemisphere is affected or why specific structures are affected. Neurobiological
      differences between the hemispheres and among various brain structures could
      provide clues to the specific effect of drugs. Increased attention to this gap in
      research will give additional insights into the etiology of drug abuse and
      provide direction for treatment.

PMID- 30090868
TI  - Barriers to Screening Pregnant Women for Domestic Violence: A Cross-Sectional
      Study.
AB  - Background information: Domestic Violence (DV) is associated with serious
      consequences to the survivor's physical, emotional, sexual, social and mental
      well-being. DV screening ensures timely detection of violence and hence promotes
      timely intervention. This timely intervention has the potential of averting
      adverse outcomes of DV to the survivor. Globally, the prevalence of DV among
      women is 35% and in Kenya its 49% among women and 13.5% among pregnant women.
      Despite the adverse outcome of DV in pregnancy, screening during pregnancy lags
      behind in Kenya. Purpose: To assess the nursing barriers to screening pregnant
      women for DV. Methodology: A cross-sectional study of 125 nurses selected by
      random sampling method was conducted at a National Maternity Hospital in Kenya.
      Data was collected for 8 weeks using researchers developed structured
      questionnaire. Data was analyzed using Statistical Package for Social Sciences
      (SPSS) version 20.0. Chi-square test was used to determine significance of
      relationships between nominal variables. A P-value of <= 0.05 was considered
      significant. Results: Study results revealed that 16% (n=8) of nurses routinely
      screened pregnant women for DV. Non-screening behavior of nurses was associated
      with lack of DV screening training during their education program (P=0.002), fear
      of the partner's reaction (P=0.004) and lack of mentors and role models in DV
      screening (P=0.005). Lack of cooperation from other health professionals was also
      associated with non-screening of DV (P=0.016). The significance of the study: The
      results of this study point to the need of developing hospital's protocols on DV
      management and considering integrating DV screening in the routine medical
      screening of pregnant women during antenatal care. Conclusion: The study showed
      that the nurse's prevalence of screening pregnant women for DV is low at 16% due
      to various barriers.

PMID- 30090869
TI  - Dynamical networks: Finding, measuring, and tracking neural population activity
      using network science.
AB  - Systems neuroscience is in a headlong rush to record from as many neurons at the
      same time as possible. As the brain computes and codes using neuron populations,
      it is hoped these data will uncover the fundamentals of neural computation. But
      with hundreds, thousands, or more simultaneously recorded neurons come the
      inescapable problems of visualizing, describing, and quantifying their
      interactions. Here I argue that network science provides a set of scalable,
      analytical tools that already solve these problems. By treating neurons as nodes
      and their interactions as links, a single network can visualize and describe an
      arbitrarily large recording. I show that with this description we can quantify
      the effects of manipulating a neural circuit, track changes in population
      dynamics over time, and quantitatively define theoretical concepts of neural
      populations such as cell assemblies. Using network science as a core part of
      analyzing population recordings will thus provide both qualitative and
      quantitative advances to our understanding of neural computation.

PMID- 30090870
TI  - Switching between internal and external modes: A multiscale learning principle.
AB  - Brains construct internal models that support perception, prediction, and action
      in the external world. Individual circuits within a brain also learn internal
      models of the local world of input they receive, in order to facilitate efficient
      and robust representation. How are these internal models learned? We propose that
      learning is facilitated by continual switching between internally biased and
      externally biased modes of processing. We review computational evidence that this
      mode-switching can produce an error signal to drive learning. We then consider
      empirical evidence for the instantiation of mode-switching in diverse neural
      systems, ranging from subsecond fluctuations in the hippocampus to wake-sleep
      alternations across the whole brain. We hypothesize that these internal/external
      switching processes, which occur at multiple scales, can drive learning at each
      scale. This framework predicts that (a) slower mode-switching should be
      associated with learning of more temporally extended input features and (b)
      disruption of switching should impair the integration of new information with
      prior information.

PMID- 30090871
TI  - Nonparametric test for connectivity detection in multivariate autoregressive
      networks and application to multiunit activity data.
AB  - Directed connectivity inference has become a cornerstone in neuroscience to
      analyze multivariate data from neuroimaging and electrophysiological techniques.
      Here we propose a nonparametric significance method to test the nonzero values of
      multivariate autoregressive model to infer interactions in recurrent networks. We
      use random permutations or circular shifts of the original time series to
      generate the null-hypothesis distributions. The underlying network model is the
      same as used in multivariate Granger causality, but our test relies on the
      autoregressive coefficients instead of error residuals. By means of numerical
      simulation over multiple network configurations, we show that this method
      achieves a good control of false positives (type 1 error) and detects existing
      pairwise connections more accurately than using the standard parametric test for
      the ratio of error residuals. In practice, our method aims to detect temporal
      interactions in real neuronal networks with nodes possibly exhibiting redundant
      activity. As a proof of concept, we apply our method to multiunit activity (MUA)
      recorded from Utah electrode arrays in a monkey and examine detected interactions
      between 25 channels. We show that during stimulus presentation our method detects
      a large number of interactions that cannot be solely explained by the increase in
      the MUA level.

PMID- 30090873
TI  - High-energy brain dynamics during anesthesia-induced unconsciousness.
AB  - Characterizing anesthesia-induced alterations to brain network dynamics provides
      a powerful framework to understand the neural mechanisms of unconsciousness. To
      this end, increased attention has been directed at how anesthetic drugs alter the
      functional connectivity between brain regions as defined through neuroimaging.
      However, the effects of anesthesia on temporal dynamics at functional network
      scales is less well understood. Here, we examine such dynamics in view of the
      free-energy principle, which postulates that brain dynamics tend to promote lower
      energy (more organized) states. We specifically engaged the hypothesis that such
      low-energy states play an important role in maintaining conscious awareness. To
      investigate this hypothesis, we analyzed resting-state BOLD fMRI data from human
      volunteers during wakefulness and under sevoflurane general anesthesia. Our
      approach, which extends an idea previously used in the characterization of neuron
      scale populations, involves thresholding the BOLD time series and using a
      normalized Hamiltonian energy function derived from the Ising model. Our major
      finding is that the brain spends significantly more time in lower energy states
      during eyes-closed wakefulness than during general anesthesia. This effect is
      especially pronounced in networks thought to be critical for maintaining
      awareness, suggesting a crucial cognitive role for both the structure and the
      dynamical landscape of these networks.

PMID- 30090872
TI  - Optimized connectome architecture for sensory-motor integration.
AB  - The intricate connectivity patterns of neural circuits support a wide repertoire
      of communication processes and functional interactions. Here we systematically
      investigate how neural signaling is constrained by anatomical connectivity in the
      mesoscale Drosophila (fruit fly) brain network. We use a spreading model that
      describes how local perturbations, such as external stimuli, trigger global
      signaling cascades that spread through the network. Through a series of simple
      biological scenarios we demonstrate that anatomical embedding potentiates sensory
      motor integration. We find that signal spreading is faster from nodes associated
      with sensory transduction (sensors) to nodes associated with motor output
      (effectors). Signal propagation was accelerated if sensor nodes were activated
      simultaneously, suggesting a topologically mediated synergy among sensors. In
      addition, the organization of the network increases the likelihood of convergence
      of multiple cascades towards effector nodes, thereby facilitating integration
      prior to motor output. Moreover, effector nodes tend to coactivate more
      frequently than other pairs of nodes, suggesting an anatomically enhanced
      coordination of motor output. Altogether, our results show that the organization
      of the mesoscale Drosophila connectome imparts privileged, behaviorally relevant
      communication patterns among sensors and effectors, shaping their capacity to
      collectively integrate information.

PMID- 30090874
TI  - Sensitivity analysis of human brain structural network construction.
AB  - Network neuroscience leverages diffusion-weighted magnetic resonance imaging and
      tractography to quantify structural connectivity of the human brain. However,
      scientists and practitioners lack a clear understanding of the effects of varying
      tractography parameters on the constructed structural networks. With diffusion
      images from the Human Connectome Project (HCP), we characterize how structural
      networks are impacted by the spatial resolution of brain atlases, total number of
      tractography streamlines, and grey matter dilation with various graph metrics. We
      demonstrate how injudicious combinations of highly refined brain parcellations
      and low numbers of streamlines may inadvertently lead to disconnected network
      models with isolated nodes. Furthermore, we provide solutions to significantly
      reduce the likelihood of generating disconnected networks. In addition, for
      different tractography parameters, we investigate the distributions of values
      taken by various graph metrics across the population of HCP subjects. Analyzing
      the ranks of individual subjects within the graph metric distributions, we find
      that the ranks of individuals are affected differently by atlas scale changes.
      Our work serves as a guideline for researchers to optimize the selection of
      tractography parameters and illustrates how biological characteristics of the
      brain derived in network neuroscience studies can be affected by the choice of
      atlas parcellation schemes.

PMID- 30090875
TI  - Multi-region proteome analysis quantifies spatial heterogeneity of prostate
      tissue biomarkers.
AB  - It remains unclear to what extent tumor heterogeneity impacts on protein
      biomarker discovery. Here, we quantified proteome intra-tissue heterogeneity
      (ITH) based on a multi-region analysis of prostate tissues using pressure cycling
      technology and SWATH mass spectrometry. We quantified 6,873 proteins and analyzed
      the ITH of 3,700 proteins. The level of ITH varied depending on proteins and
      tissue types. Benign tissues exhibited more complex ITH patterns than malignant
      tissues. Spatial variability of ten prostate biomarkers was validated by
      immunohistochemistry in an independent cohort (n=83) using tissue microarrays.
      PSA was preferentially variable in benign prostatic hyperplasia, while GDF15
      substantially varied in prostate adenocarcinomas. Further, we found that DNA
      repair pathways exhibited a high degree of variability in tumorous tissues, which
      may contribute to the genetic heterogeneity of tumors. This study conceptually
      adds a new perspective to protein biomarker discovery: it suggests that recent
      technological progress should be exploited to quantify and account for spatial
      proteome variation to complement biomarker identification and utilization.

PMID- 30090876
TI  - Human Adenoviruses, Cholesterol Trafficking, and NF-kappaB Signaling.
AB  - The interplay between viruses and host factors regulating inflammatory or
      cytotoxic responses directed against infected cells is well documented. Viruses
      have evolved a wide array of mechanisms that strike a balance between the
      elimination of virus and immune-mediated tissue injury by antiviral immune
      responses. The topic of this mini-review is a series of recent studies
      demonstrating a link between cholesterol trafficking and innate immune responses
      in cells infected with human adenoviruses that provide the backbone of commonly
      used vectors in gene medicine. Besides revealing an unexpected role for lipid
      metabolism in immune evasion, these studies have important implications for
      understanding the molecular basis of cholesterol trafficking in normal cells and
      various disease states. They also describe a previously unappreciated host-virus
      interaction that may be employed by other pathogens to interfere with the host
      innate immune system.

PMID- 30090877
TI  - Heplisav-B vaccination for the prevention of hepatitis B virus infection in
      adults in the United States.
AB  - The prevalence of hepatitis B virus (HBV) infections is a worldwide issue that
      can lead to both acute and chronic complications with increased morbidity and
      mortality in affected individuals. Current methods of preventing HBV infections
      primarily include building patient immunity through administration of hepatitis B
      vaccinations starting at birth. Certain at-risk individuals, including those with
      occupational exposure to pathogenic bodily fluids, those who are sexually active
      or intravenous drug users, are recommended to receive some form of hepatitis B
      vaccination. The current standard of hepatitis B vaccination in the United States
      is the Engerix-B vaccine, which consists of a three-dose regimen over a 6-month
      time period. A new hepatitis B vaccine, Heplisav-B, has been approved for adults
      in the United States and requires only two doses over 1 month. The unique dosing
      schedule of Heplisav-B provides the potential for increasing patient compliance
      and therefore can aid in the effort toward protecting individuals from developing
      an HBV infection. Results from clinical trials showed that Heplisav-B compared
      favorably with Engerix-B in safety and efficacy profiles. This paper provides a
      review of the pharmacology, safety, clinical trials and indications for use for
      the Heplisav-B vaccine in the United States.

PMID- 30090878
TI  - Glecaprevir/pibrentasvir for the treatment of chronic hepatitis C virus infection
      in adults.
AB  - The fixed-dose combination of glecaprevir (GLE), a nonstructural protein 3/4A
      (NS3/4A) protease inhibitor, and pibrentasvir (PIB), an NS5A inhibitor, was
      recently approved for the treatment of adult patients with chronic hepatitis C
      virus (HCV) genotypes 1-6 (GT-1-6) without cirrhosis or with compensated
      cirrhosis, and for the treatment of HCV GT-1 patients who have failed treatment
      with either NS5A inhibitors or NS3/4A protease inhibitors, but not both. This
      combination, administered over 8 or 12 weeks, has resulted in high cure rates in
      all six HCV genotypes, including patients with HIV coinfection. GLE/PIB was well
      tolerated, with the most common adverse events being headache and fatigue.
      GLE/PIB is recommended to be taken as three tablets (total daily dose: GLE 300 mg
      and PIB 120 mg) orally once daily with food. No dose adjustment is required in
      patients with any degree of renal impairment or in patients undergoing
      hemodialysis. Dose adjustment is also not required in patients with Child-Pugh A
      liver disease. However, the use of GLE/PIB is not recommended in patients with
      moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment.

PMID- 30090879
TI  - Telotristat ethyl for the treatment of carcinoid syndrome diarrhea not controlled
      by somatostatin analogues.
AB  - Telotristat ethyl (Xermelo), developed by Lexicon Pharmaceuticals, is an oral
      tryptophan hydroxylase inhibitor blocking peripheral conversion of tryptophan to
      serotonin (5-hydroxytryptamine [5-HT]). It was approved by the U.S. Food and Drug
      Administration (FDA) in February 2017 and by the European Commission in September
      2017 for patients with carcinoid syndrome in whom diarrhea is not adequately
      controlled by somatostatin analogues (SSAs). Diarrhea, secondary to the release
      of serotonin, is the predominant gastrointestinal symptom in patients with
      carcinoid syndrome and has a significant impact on patients' quality of life.
      Telotristat is not meant for all patients with diarrhea and carcinoid syndrome.
      Prescribing of telotristat for patients with diarrhea refractory to SSAs requires
      careful consideration and an approach that involves identifying and ruling out
      other common causes of diarrhea in patients with carcinoid syndrome. Delineating
      the timing of diarrhea and whether it occurs in patients with stable disease
      versus cancer progression can help identify the right drug candidates for
      therapy.

PMID- 30090880
TI  - Tildrakizumab: monoclonal antibody against IL-23p19 for moderate to severe
      psoriasis.
AB  - Tildrakizumab is a monoclonal antibody that binds to the p19 subunit of
      interleukin (IL)-23. Studies examining affected skin in psoriatic patients showed
      significant changes in the cellular, cytokine and gene expression profiles of
      psoriatic lesions as a result of treatment with tildrakizumab, as well as
      significant changes in clinical measures of disease activity. These studies
      demonstrated significant clinical responses in psoriasis with significant
      improvements found in the percentage of patients achieving a Physician Global
      Assessment score of 0 or 1, and a 75%, 90% or 100% improvement in the Psoriasis
      Area and Severity Index (PASI 75, PASI 90, PASI 100). These changes were
      accompanied by a low frequency of adverse effects. This combination of efficacy
      and safety led to the approval of tildrakizumab in 2018 by the U.S. Food and Drug
      Administration (FDA) for use in adult patients with moderate to severe psoriasis.

PMID- 30090881
TI  - The 9th Annual Biosimilar Asia 2018 (May 16-17, 2018 - Shanghai, China).
AB  - The 9th Annual Biosimilar Asia, an event hosted by ICB Asia, was held at the
      Hilton Shanghai Hongqiao from May 16 to 17. It was held simultaneously with
      Biomanufacturing Asia, and Cell Line Development and Engineering Asia. These
      three events formed Biopharma Development and Production (BDP) 2018. The BDP 2018
      event had more than 60 sessions, over 70 speakers and more than 300 companies
      from around the world.

PMID- 30090882
TI  - Towards the development of chitosan nanoparticles for plutonium pulmonary
      decorporation.
AB  - Since the 1940s, great amounts of Plutonium (Pu) have been produced for both
      military and civil purposes. Until now, the standard therapy for decorporation
      following inhalation has been the intravenous injection of
      diethylenetriaminepentaacetic acid ligand (Ca-DTPA form). This method offers a
      strong complexing constant for Pu(iv) but has poor chemical specificity,
      therefore its efficacy is limited to actinides present in the blood.
      Consequently, there is no decorporation treatment currently available which
      efficiently removes the intracellular Pu(iv) trapped in the pulmonary
      macrophages. Our research shows that a nanoparticle approach could be of
      particular interest due to large contact area and ability to target the retention
      compartments of the lungs. In this study, we have focused on the inhalation
      process involving forms of Pu(iv) with poor solubility. We explored the design of
      biocompatible nanoparticles able to target the macrophages in the lung alveoli
      and to chelate the forms of Pu(iv) with poor solubility. Nanoparticle formation
      was achieved through an ionic cross-linking concept using a polycationic polymer
      and an anionic chelate linker. We chose N-trimethyl chitosan, for its
      biocompatibility, as the polycationic polymer base of the nanoparticle and the
      phosphonic analogue of DTPA, diethylenetriamine-pentamethylenephosphonic acid
      (DTPMP) as the anionic chelating linker in forming NPs TMC-DTPMP. The synthesis
      and physico-chemical characterization of these NPs are presented. Secondly, the
      complexation mechanisms of TMC-DTPMP NPs with Thorium (Th(iv)) are discussed in
      terms of efficiency and structure. The Extended X-Ray Absorption Fine Structure
      (EXAFS) of the TMC-DTPMP complex with Th(iv) as well as Pu(iv) are defined and
      completed with DFT calculations to further delineate the plutonium coordination
      sphere after complexation. Finally, preliminary cytotoxicity tests onto
      macrophages were assayed.

PMID- 30090883
TI  - Strategies of alloying effect for regulating Pt-based H2-SCR catalytic activity.
AB  - Alloying Pt with 3d transition metals results in the d-band center moving away
      from the Fermi level, creating compressive strain. The adsorption strength of the
      reactants should not be too strong or too weak. The presence of compressive
      strain, which can increase the orbital overlap between *H and *O, results in the
      reduction of energy barriers of H-assisted N-O bond activation in terms of the
      Langmuir-Hinshelwood (L-H) reaction route. Our findings provide guidelines to
      design more efficient H2-SCR catalysts.

PMID- 30090884
TI  - Responsive upconversion nanoprobe for monitoring and inhibition of EBV-associated
      cancers via targeting EBNA1.
AB  - Non-responsive emission enhancement is the disadvantage of upconversion
      nanomaterials (UCNM) when compared with conventional organic based agents for
      molecular imaging. We herein show a new strategy by conjugating
      NaGdF4:Yb3+,Er3+@NaGdF4 (UCNP) with peptides to achieve responsive UC emission
      enhancement upon binding to a targeted protein - EBNA1. EBNA1 is a well-known
      viral latent protein for the EBV-associated cancer. Peptide-coating of the
      functionalized core-shell nanoparticle diminishes upconverted emission intensity
      drastically. However, the peptide-coated UCNP shows selective and responsive UC
      emission enhancement via aggregation with the targeted protein. This phenomenon
      paves a new way for UCNM in molecular imaging.

PMID- 30090885
TI  - Mesoporous MnCo2S4 nanosheet arrays as an efficient catalyst for Li-O2 batteries.
AB  - Ternary metal sulfides and ternary metal oxides have received much attention as
      potential electrodes for high performance rechargeable batteries. Herein, MnCo2S4
      nanosheets are grown on carbon paper (MCS/CP) via facile electrodeposition
      followed by low temperature vulcanization for application in Li-O2 batteries for
      the first time. The electrochemical performance of freestanding, binder-free
      MCS/CP oxygen electrodes is compared with those prepared from MnCo2O4 nanosheets
      on CP (MCO/CP). The MCS/CP electrode delivers an extremely high initial specific
      capacity of 10 760 mA h g-1, twice that of MCO/CP. The former electrode sustains
      96 cycles at an upper limit capacity of 500 mA h g-1 at 200 mA g-1, whereas the
      latter counterpart survives only a few cycles with a poor round trip efficiency.
      The superior performance of MCS/CP is in part proven by the four times higher
      electrical conductivity and 250% higher lithium diffusion coefficient than
      MCO/CP. In addition, the 3D interconnected web of 2D MCS nanosheets offers a few
      micrometer open voids to accommodate discharge products and a large surface area
      with internal mesopores providing abundant active sites. The density functional
      theory calculations reveal a lower adsorption energy for LiO2 on the surface of
      MCS than on MCO, which is responsible for the lower OER overpotential and the
      higher catalytic ability of MCS/CP. The predicted density of states signifies
      metallic properties of MCS in agreement with the high electrical conductivity of
      MCS/CP.

PMID- 30090886
TI  - Correction: Dibenzofuran-4,6-bis(oxazoline) (DBFOX). A novel trans-chelating
      bis(oxazoline) ligand for asymmetric reactions.
AB  - Correction for 'Dibenzofuran-4,6-bis(oxazoline) (DBFOX). A novel trans-chelating
      bis(oxazoline) ligand for asymmetric reactions' by Kennosuke Itoh et al., Org.
      Biomol. Chem., 2018, DOI: 10.1039/c8ob01010 b.

PMID- 30090887
TI  - Application of new nanoparticle structures as catalysts: general discussion.

PMID- 30090888
TI  - A clickable NHC-Au(i)-complex for the preparation of stimulus-responsive
      metallopeptide amphiphiles.
AB  - We report the synthesis of an alkyne functionalised NHC-Au(i)-complex which is
      conjugated with amphiphilic oligopeptides using a copper(i) catalysed
      cycloaddition. The resulting Au(i)-metalloamphiphiles are shown to self-assemble
      into charge-regulated stimulus-responsive supramolecular polymers in water via a
      weakly cooperative polymerisation mechanism.

PMID- 30090890
TI  - SnS2/TiO2 nanohybrids chemically bonded on nitrogen-doped graphene for lithium
      sulfur batteries: synergy of vacancy defects and heterostructures.
AB  - Despite their high-energy density, low cost and environmental friendliness, the
      commercial application of lithium-sulfur batteries (LSBs) has been plagued by
      their severe capacity decay during long-term cycling caused by polysulfide
      shuttling. Herein, we demonstrate a synergetic vacancy and heterostructure
      engineering strategy using a nitrogen-doped graphene/SnS2/TiO2 (denoted as
      NG/SnS2/TiO2) nanocomposite to enhance the electrochemical performance of LSBs.
      It is noted that plentiful sulfur vacancy (Vs) defects and nanosized
      heterojunctions are created on the NG/SnS2/TiO2 composite as proved using
      electron paramagnetic resonance, transmission electron microscopy and X-ray
      photoelectron spectroscopy, which can serve as strong adsorption and activation
      sites for polar polysulfide intermediates, prevent their dissolution/shuttling,
      and accelerate their redox reaction. The novel NG/SnS2/TiO2-S cathode delivers a
      high initial capacity of 1064 mA h g-1 at 0.5 C and a high capacity retention
      rate of 68% after 500 cycles at 0.5 C.

PMID- 30090891
TI  - The 6pi-azaelectrocyclization of azatrienes. Synthetic applications in natural
      products, bioactive heterocycles, and related fields.
AB  - Covering: 2006 to 2018The application of the 6pi-azaelectrocyclization of
      azatrienes as a key strategy for the synthesis of natural products, their analogs
      and related bioactive or biomedically-relevant compounds (from 2006 to date) is
      comprehensively reviewed. Details about reaction optimization studies, relevant
      reaction mechanisms and conditions are also discussed.

PMID- 30090892
TI  - Computational structure determination of novel metal-organic frameworks.
AB  - A structure prediction tool has been developed to guide the discovery of MOF
      materials. This computational strategy has been trained over a series of existing
      MOFs and further successfully applied in tandem with an experimental effort to
      produce novel Zr MOFs based on naturally occurring carboxylic acids.

PMID- 30090893
TI  - A multi-functional macrophage and tumor targeting gene delivery system for the
      regulation of macrophage polarity and reversal of cancer immunoresistance.
AB  - To achieve effective tumor eradication using anti-tumor immunotherapies, a fusion
      peptide functionalized gene delivery system for macrophage and tumor targeting
      delivery of the plasmid DNA encoding the IL-12 gene (pDNA IL-12) was prepared for
      macrophage re-polarization as well as reversal of cancer immunosuppression. A
      fusion peptide containing the tuftsin sequence that can interact with Fc
      receptors and neuropilin-1, and hyaluronic acid (HA) that can interact with CD44
      were introduced into the delivery system by self-assembly to form
      peptide/hyaluronic acid/protamine/CaCO3/DNA nanoparticles (PHNP) with both
      macrophage targeting and tumor targeting capabilities. PHNP provides an efficient
      immunoregulation on J774A.1 cells to shift the anti-inflammatory M2 phenotype to
      the anti-tumor M1 phenotype with enhanced secretion of pro-inflammatory cytokines
      and increased expression of M1 markers. Owing to the improved delivery efficiency
      caused by the fusion peptide and HA, the transfection mediated by multi
      functional PHNP can up-regulate IL-12 as well as down-regulate IL-10 and IL-4
      more effectively as compared with the nanoparticles without HA and/or peptide
      decoration. More importantly, the gene delivery system can also deliver pDNA IL
      12 to targeted cancerous HeLa cells to realize the secretion of IL-12. PHNP not
      only enables tumorous cells to produce pDNA IL-12, but also down-regulates CD47
      and up-regulate CD80 and HLA-1 in the malignant cells, indicating that the gene
      delivery system can effectively reverse tumor induced immunosuppression.

PMID- 30090894
TI  - Nanocellulose/TiO2 composites: preparation, characterization and application in
      the photocatalytic degradation of a potential endocrine disruptor, mefenamic
      acid, in aqueous media.
AB  - Nanocellulose (NC)-supported TiO2 nanoparticles, termed NCTs, were prepared by an
      ultrasonic impregnation method. The as-synthesized NCTs were thoroughly
      characterized and studied for the photodegradation of mefenamic acid (MEF), an
      anthranilic acid derivative drug. The adsorption potential of NCTs increased with
      TiO2 loading and 10 wt% TiO2 NCT showed the highest sorption potential.
      Adsorption kinetics of MEF onto NC and NCTs indicated that the equilibrium was
      reached within 50 min. A pseudo-second-order model clearly represented the
      experimental kinetic data and demonstrated that the MEF sorption was mainly
      chemisorption. Equilibrium sorption analysis indicated that the adsorption
      followed the Langmuir model with a monolayer sorption capacity of 22.43 mg g-1
      for 10 wt% TiO2 NCT. The photocatalytic degradation rates of NCTs were identical
      with respect to their adsorption capacities, and the apparent rate constant
      (kapp) values indicated that the amount of TiO2 in NCTs played a vital role in
      the degradation of MEF. Furthermore, 10 wt% TiO2 NCT showed excellent catalytic
      activity and reusability even after five cycles of photodegradation.

PMID- 30090895
TI  - Microfluidic filter device with nylon mesh membranes efficiently dissociates cell
      aggregates and digested tissue into single cells.
AB  - Tissues are increasingly being analyzed at the single cell level in order to
      characterize cellular diversity and identify rare cell types. Single cell
      analysis efforts are greatly limited, however, by the need to first break down
      tissues into single cell suspensions. Current dissociation methods are
      inefficient, leaving a significant portion of the tissue as aggregates that are
      filtered away or left to confound results. Here, we present a simple and
      inexpensive microfluidic device that simultaneously filters large tissue
      fragments and dissociates smaller aggregates into single cells, thereby improving
      single cell yield and purity. The device incorporates two nylon mesh membranes
      with well-defined, micron-sized pores that operate on aggregates of different
      size scales. We also designed the device so that the first filtration could be
      performed under tangential flow to minimize clogging. Using cancer cell lines, we
      demonstrated that aggregates were effectively dissociated using high flow rates
      and pore sizes that were smaller than a single cell. However, pore sizes that
      were less than half the cell size caused significant damage. We then improved
      results by passing the sample through two filter devices in series, with single
      cell yield and purity predominantly determined by the pore size of the second
      membrane. Next, we optimized performance using minced and digested murine kidney
      tissue samples, and determined that the combination of 50 and 15 MUm membranes
      was optimal. Finally, we integrated these two membranes into a single filter
      device and performed validation experiments using minced and digested murine
      kidney, liver, and mammary tumor tissue samples. The dual membrane microfluidic
      filter device increased single cell numbers by at least 3-fold for each tissue
      type, and in some cases by more than 10-fold. These results were obtained in
      minutes without affecting cell viability, and additional filtering would not be
      required prior to downstream applications. In future work, we will create
      complete tissue analysis platforms by integrating the dual membrane microfluidic
      filter device with additional upstream tissue processing technologies, as well as
      downstream operations such as cell sorting and detection.

PMID- 30090896
TI  - Effect of microparticulation and xanthan gum on the stability and lipid digestion
      of oil-in-water emulsions stabilized by whey protein.
AB  - Since lipid digestion is an interfacial process, food emulsions are increasingly
      being seen as a mechanism for controlling lipid uptake. Oil-in-water emulsions
      stabilized by whey protein (WP) and protein-xanthan gum (XG) mixtures were
      designed to investigate the influence of interfacial structures on lipid
      digestion using an in vitro digestion model. The interfacial layers with
      different structures were designed using microparticulated whey protein (MWP) and
      MWP-XG mixtures. The increase in the volume average diameter of proteins
      indicated that the WPs aggregated to form micro-particles during
      microparticulation. The increase in the protein surface hydrophobicity index and
      the measurement results from the Magnetic Resonance Imaging System indicated that
      the protein hydrophilic groups were embedded and that the protein hydrophobic
      groups were exposed. Under in vitro conditions, the emulsions stabilized by
      microparticulated whey proteins and protein-XG mixtures were more stable than the
      WP emulsions, and the microparticulated whey proteins and protein-XG mixtures
      were more effective for decreasing the digestion rate, as shown by the stability
      analysis and free fatty acid release rates. These results help elucidate the
      influence of the interfacial structure on lipid digestion. The control of lipid
      digestibility within the gastrointestinal tract might be important for the design
      and development of reduced-fat foods and novel functional foods for controlling
      bioactive release.

PMID- 30090897
TI  - Where do photogenerated holes at the g-C3N4/water interface go for water
      splitting: H2O or OH-?
AB  - Graphitic carbon nitride (g-C3N4), a metal-free two-dimensional photocatalyst,
      has drawn increasing attention due to its application in photocatalytic water
      splitting. However, its quantum efficiency is limited by the poor performance of
      the oxygen evolution reaction (OER). Therefore, it is important to clarify the
      behavior of photogenerated holes in the OER. In this work, we investigate the
      energy level alignment using the GW method and the exciton properties using the
      Bethe-Salpeter equation within the ab initio many-body Green's function theory at
      the g-C3N4/water interface. We found that the g-C3N4 substrate can elevate energy
      levels of OH- and H2O molecules at the interface by up to 0.6 eV. This effect can
      make the electronic levels of OH- surpass the valence band maximum (VBM) of g
      C3N4. However, orbital energies of H2O molecules remain far below the VBM of g
      C3N4. This indicates that a photogenerated hole after exciting g-C3N4 can relax
      to OH- instead of neutral H2O. Moreover, OH- could be directly oxidized through
      electron transfer from OH- to g-C3N4 by light near the optical absorption edge of
      g-C3N4, which is beneficial for efficient carrier separation at the interface.

PMID- 30090898
TI  - Cobalt(ii) acyl intermediates in carbon-carbon bond formation and oxygenation.
AB  - The organocobalt scorpionate compounds ToMCoR (ToM = tris(4,4-dimethyl-2
      oxazolinyl)phenylborate; R = Bn, 1; CH2SiMe3, 2; Ph, 3; Et, 4; nBu, 5; Me, 6)
      react in carbonylation, oxidation, and carboxylation reactions via pathways that
      are distinctly influenced by the nature of the organometallic moiety. The
      compounds are prepared by reaction of ToMCoCl with the corresponding
      organolithium or organopotassium reagents. Compounds 1-6 were characterized by 8
      line hyperfine coupling to cobalt in EPR spectra and solution phase magnetic
      measurements (MUeff = 4-5MUB) as containing a high-spin cobalt(ii) center. The UV
      Vis spectra revealed an intense diagnostic band at ca. 700 nm (epsilon > 1000 M-1
      cm-1) associated with the tetrahedral organocobalt(ii) center that was assigned
      to a d <- d transition on the basis of configuration interaction (CI)
      calculations. Complexes 1-6 react rapidly with CO to form equilibrating mixtures
      of the low spin organocobalt carbonyl ToMCo(R)CO, acyl ToMCoC([double bond,
      length as m-dash]O)R, and acyl carbonyl ToMCo{C([double bond, length as m
      dash]O)R}CO. The 1H and 11B NMR spectra contained only one set of signals for the
      CO-treated solutions, whereas the solution-phase IR spectra contained up to two
      nuCO and three nuC([double bond, length as m-dash]O)R signals with intensities
      varying depending on the R group (R = Bn, 7; CH2SiMe3, 8; Ph, 9; Et, 10; nBu, 11;
      Me, 12). Single crystal X-ray diffraction of ToMCo{C([double bond, length as m
      dash]O)Et}CO (10) supports its assignment as a square pyramidal cobalt(ii) acyl
      carbonyl complex. Upon evaporation of volatiles, solutions of 8-12 revert to the
      CO-free organocobalt starting materials 2-6, whereas attempts to isolate benzyl
      derived 7 provide an unusual alpha-alkoxyketone species, characterized by single
      crystal X-ray diffraction. Despite the differences observed in the carbonylation
      of 1-6 as a result of varying the R group, compounds 7-12 all react rapidly with
      O2 through an oxygenation pathway to afford the corresponding carboxylate
      compounds ToMCoO2CR (R = Bn, 13; CH2SiMe3, 14; Ph, 15; Et, 16; nBu, 17; Me, 18).
      In contrast, the insertion of CO2 into the Co-C bond in 1-6 requires several days
      to weeks.

PMID- 30090899
TI  - Synthesis, optical properties and theoretical modelling of discrete emitting
      states in doped silicon nanocrystals for bioimaging.
AB  - The creation of multiple emission pathways in quantum dots (QDs) is an exciting
      prospect with fundamental interest and optoelectronic potential. For the first
      time, we report multiple emission pathways in semiconductor nanocrystals (NCs)
      where the number of emission pathways desired is controlled by the number of
      dopant atoms per quantum dot. The origin of additional emission pathways is
      explained by interactions between dopant states and NC energy levels. Density
      functional theory (DFT) calculations of undoped 2.3 nm silicon (Si NCs) and the
      same NCs doped with 2 interstitial Cu atoms show good agreement to experiment.
      Such calculations provide valuable data to explain the changes in optical
      transitions due to the Cu dopant in terms of transition energies, quantum yield
      and dopant position as a function of dopants per NC. Changes in the optical
      properties of Si NCs induced by dopant concentration include extended excitation
      range and enhanced absorption coefficients, emission redshifts of up to 60 nm,
      and a two-fold increase in quantum yields up to 22%. The optical properties of
      doped NCs lead to significant bioimaging improvements illustrated by in vitro
      cell imaging, including redshifted excitation wavelengths away from natural
      autofluorescence and enhanced fluorescent signals.

PMID- 30090900
TI  - Upgrading gasoline to high octane numbers using a zeolite-like metal-organic
      framework molecular sieve with ana-topology.
AB  - Separation of paraffin isomers is of great importance in the refining industry
      because of their potential applications for energy efficiency, as reflected by
      their associated Research Octane Number (RON) values. Here, we report the
      synthesis of the first zeolite-like metal-organic framework (ZMOF) with ana
      topology that displays helicoidally/cylindrically-shaped channels with a pore
      aperture size of ca. 3.8 * 6.2 A. Markedly, such structural features offer
      potential for the selective separation of linear, and mono- and dibranched
      paraffins. Largely due to its tuned pore size and the presence of ions in the
      channels, ana-ZMOF possesses an excellent uniform charge density that allows the
      kinetic separation of n-pentane versus iso-pentane and n-butane vs. iso-butane,
      as well as the molecular exclusion of 2,2,4-trimethyl pentane.

PMID- 30090905
TI  - Valley-contrasting optics of interlayer excitons in Mo- and W-based bulk
      transition metal dichalcogenides.
AB  - Recently, spatially indirect ("interlayer") excitons have been discovered in bulk
      2H-MoTe2. They are theoretically predicted to exist in other Mo-based transition
      metal dichalcogenides (TMDCs) and are expected to be present in W-based TMDCs as
      well. We investigate interlayer excitons (XIL) in bulk 2H-MoSe2 and 2H-WSe2 using
      valley-resolved magneto-reflectance spectroscopy under high magnetic fields of up
      to 29 T combined with ab initio GW-BSE calculations. In the experiments, we
      observe interlayer excitons in MoSe2, while their signature is surprisingly
      absent in WSe2. In the calculations, we find that interlayer excitons exist in
      both Mo- and W-based TMDCs. However, their energetic positions and their
      oscillator strengths are remarkably different. In Mo-based compounds, the
      interlayer exciton resonance XIL is clearly separated from the intralayer exciton
      X1sA and has a high amplitude. In contrast, in W-based compounds, XIL is close in
      energy to the intralayer A exciton X1sA and possesses a small oscillator
      strength, which explains its absence in the experimental data of WSe2. Our
      combined experimental and theoretical observations demonstrate that interlayer
      excitons can gain substantial oscillator strength by mixing with intralayer
      states and hence pave the way for exploring interlayer exciton physics in Mo
      based bulk transition metal dichalcogenides.

PMID- 30090907
TI  - Highly sulphated cellulose: a versatile, reusable and selective desilylating
      agent for deprotection of alcoholic TBDMS ethers.
AB  - A mild, efficient and rapid protocol was developed for the deprotection of
      alcoholic TBDMS ethers using a recyclable, eco-friendly highly sulphated
      cellulose sulphate acid catalyst in methanol. This acid catalyst selectively
      cleaves alcoholic TBDMS ethers in bis-TBDMS ethers containing both alcoholic and
      phenolic TBDMS ether moieties.

PMID- 30090908
TI  - Fragment motion in motor molecules: basic concepts and application to intra
      molecular rotations.
AB  - The complex motion of atoms inside large molecules can be analyzed by considering
      translation, rotation, and flexibility of corresponding molecular fragments and
      by applying classical mechanics based on Pulay forces on the atoms, as in
      molecular dynamics. We propose a fragment motion analysis that provides a basic
      qualitative understanding of the motion of the different molecular components.
      Further, it can help to describe or design simplified fragment motions, e.g. the
      rotation of a rotator with respect to its stator counterpart in a rotor molecule,
      despite the higher actual complexity due to flexibility of rotator and stator or
      due to a variable rotation axis. The formal aspects of the fragment motion
      analysis are discussed in detail. Its application is illustrated by the
      rotational motion inside the BTP-BCO molecule and by rotational transitions
      between cis- and trans-stilbene isomers.

PMID- 30090909
TI  - Graphite-based selectorless RRAM: improvable intrinsic nonlinearity for array
      applications.
AB  - Selectorless graphite-based resistive random-access memory (RRAM) has been
      demonstrated by utilizing the intrinsic nonlinear resistive switching (RS)
      characteristics, without an additional selector or transistor for low-power RRAM
      array application. The low effective dielectric constant value (k) layer of
      graphite or graphite oxide is utilized, which is beneficial in suppressing sneak
      path currents in the crossbar RRAM array. The tail-bits with low nonlinearity can
      be manipulated by the positive voltage pulse, which in turn can alleviate
      variability and reliability issues. Our results provide additional insights for
      built-in nonlinearity in 1R-only selectorless RRAMs, which are applicable to the
      low-power memory array, ultrahigh density storage, and in-memory neuromorphic
      computational configurations.

PMID- 30090910
TI  - Luminescent switch sensors for the detection of biomolecules based on metal
      organic frameworks.
AB  - Metal-organic frameworks (MOFs) as sensing materials have experienced explosive
      growth in recent years due to their intrinsic merits, such as structural
      diversity, high porosity, large surface area, extraordinary adsorption
      affinities, etc. Biomolecules such as DNA, protein, and vitamins play vital roles
      in metabolism. Moreover, the sensitive detection of biomolecules is of importance
      in the disease prevention and treatment. This review intends to provide an update
      on the recent progress in the detection of various biomolecules via MOF-based
      luminescent sensors. MOFs are successful in the detection of DNA, RNA, protein,
      and other biomolecules. MOF-based luminescent sensors function by utilizing
      different mechanisms, including luminescent responses of enhancement and
      quenching, which are defined as "turn-on" and "turn-off" responses, respectively.
      Then, a short comparison of the "turn-on" and "turn-off" types of sensors is also
      made.

PMID- 30090911
TI  - Effects of elevated production of autochthonous dissolved organic matter on the
      freely dissolved concentration of cadmium.
AB  - Eutrophication enhances the production of autochthonous dissolved organic matter
      (DOM), which is a major driving factor behind the impairment of many aquatic
      ecosystems. In a mesocosm study, we investigated the effects of the abundance and
      composition of DOM on the potential bioavailability of cadmium (Cd) caused by
      eutrophication, using three-dimensional excitation-emission matrix fluorescence
      spectroscopy integrated with tangential flow ultrafiltration technology. The
      complexing capacity of DOM-Cd and the sorption distribution coefficient between
      DOM and the bulk solution was calculated based on a 1 : 1 complexation model. The
      fluorescent DOM was decomposed into three components (one protein-like and two
      humic-like substances) by parallel factor analysis (PARAFAC). The fluorescence
      intensity of the protein-like substance was significantly correlated with the
      concentration of chlorophyll a (Chl-a), indicating that the protein-like
      substance mainly originated from the release or decomposition of algal cells. The
      complexing capacity of DOM-Cd decreased from 997 MUmol Cd per gram dissolved
      organic carbon (DOC) to 884 MUmol Cd per gram DOC with an increase in the
      proportion of autochthonous protein-like substances. However, the total Cd
      complexing capacity of DOM was still high during the algal bloom due to the
      increase of DOM abundance. The proportion of freely dissolved concentration of Cd
      to total Cd concentration decreased from 50% to 20%, suggesting that the
      potential bioavailability of Cd was reduced.

PMID- 30090912
TI  - Bi2O3 monolayers from elemental liquid bismuth.
AB  - Atomically thin, semiconducting transition and post transition metal oxides are
      emerging as a promising category of materials for high-performance oxide
      optoelectronic applications. However, the wafer-scale synthesis of crystalline
      atomically thin samples has been a challenge, particularly for oxides that do not
      present layered crystal structures. Herein we use a facile, scalable method to
      synthesise ultrathin bismuth oxide nanosheets using a liquid metal facilitated
      synthesis approach. Monolayers of alpha-Bi2O3 featuring sub-nanometre thickness,
      high crystallinity and large lateral dimensions could be isolated from the liquid
      bismuth surface. The nanosheets were found to be n-type semiconductors with a
      direct band gap of ~3.5 eV and were suited for developing ultra violet (UV)
      photodetectors. The developed devices featured a high responsivity of ~400 AW-1
      when illuminated with 365 nm UV light and fast response times of ~70 MUs. The
      developed methods and obtained nanosheets can likely be developed further towards
      the synthesis of other bismuth based atomically thin chalcogenides that hold
      promise for electronic, optical and catalytic applications.

PMID- 30090914
TI  - A bio-inspired photonic nitrocellulose array for ultrasensitive assays of single
      nucleic acids.
AB  - Here we report a bio-inspired photonic nitrocellulose array for ultrasensitive
      nucleic-acid detection. The patterned photonic nitrocellulose array is inspired
      by the Stenocara beetle living in the desert, which can collect water on its
      bumpy back surface from early morning fogs so that spontaneous generation of
      separated reaction droplets for loop-mediated isothermal amplification (LAMP)
      based detection is enabled. Owing to the slow-photon effect of the photonic
      nitrocellulose, the fluorescence signal of calcein produced during the LAMP
      reaction can be effectively enhanced (up to 32 fold), which results in
      dramatically improved sensitivity for the detection of single nucleic acids in 40
      min. We demonstrate that Staphylococcus aureus (SA) DNA can be quantitatively
      detected with a limit-of-detection of 0.60 copy per MUL. The consumption of
      reagents and sample is also remarkably reduced owing to the highly decreased dead
      volume of the nitrocellulose substrate. Therefore, this bio-inspired photonic
      nitrocellulose array is promising for carrying out inexpensive, ultrasensitive,
      and high-throughput nucleic-acid detection under resource-limited settings.

PMID- 30090916
TI  - "Choose-a-size" control in the synthesis of sucrose based urea and thiourea
      macrocycles.
AB  - Highly efficient synthesis of monomeric and dimeric thiourea macrocycles with a
      per-O-benzylated sucrose scaffold is reported. Application of flow synthesis
      results in exclusive formation of a monomer in 79% yield. Batch synthesis
      provides two isomeric dimers in 85% yield. Dimers are capable of anion binding
      via two thiourea groups acting cooperatively.

PMID- 30090918
TI  - Evaluation of a Brief Dermatologist-Delivered Intervention vs Usual Care on Sun
      Protection Behavior.
AB  - Importance: Despite receiving dermatologic care, many patients with or without a
      history of skin cancer either do not use sun protection or fail to use it in an
      effective manner. Objective: To examine the association of a brief dermatologist
      delivered intervention vs usual care with patient satisfaction and sun protection
      behavior. Design, Setting, and Participants: A longitudinal controlled cohort
      study among adults receiving dermatology care was conducted from April 25 to
      November 6, 2017, at 2 dermatologic clinic sites within a Northeastern health
      care system to compare outcomes associated with the intervention with that of
      usual care on 1- and 3-month patient outcomes. The sample consisted primarily of
      non-Hispanic white patients aged 21 to 65 years. Participants were assigned to
      the intervention group (n = 77) or the control group (n = 82) based on the site
      location of their dermatologists. Interventions: The intervention (<3 minutes)
      was delivered by dermatologists during a skin examination or the suturing phase
      of skin cancer surgery. The intervention consisted of 6 components targeting sun
      risk and protective behaviors. Main Outcomes and Measures: First, patient's
      satisfaction with the dermatologist's communication was assessed. Second, the
      association of the intervention with changing sun protection behavior of the
      patient was examined. Results: Patients in the intervention group (46 women and
      31 men; mean [SD] age, 52.4 [9.6] years) rated dermatologist-patient
      communication more positive compared with patients in the control group (59 women
      and 23 men; mean [SD] age, 51.4 [11.3 years]). Eighteen percent (14 of 77) of
      patients in the intervention group reported 1 or more sunburns 1 month after the
      intervention compared with 35% (29 of 82) of patients in the control group (P =
      .01). No differences in report of sunburns were seen at the 3-month follow-up.
      Patients in the intervention group reported increased use of sunscreen across 3
      months (face: intervention, increased 12% and controls, decreased 4%; P = .001;
      body: intervention, increased 12% and controls, decreased 1%; P = .02;
      reapplication: intervention, increased 15% and controls, remained stable; P =
      .002). Conclusions and Relevance: The intervention was delivered by
      dermatologists after minimal standardized training and resulted in a higher level
      of satisfaction with dermatologist-patient communication and improved sun
      protection behavior among patients across several months.

PMID- 30090919
TI  - Randomized Clinical Trial Needed to Confirm Whether Dalcetrapib Improves Outcomes
      for Specific ADCY9 Genotype.

PMID- 30090920
TI  - The Role of Obesity in the Association Between Posttraumatic Stress Disorder and
      Incident Diabetes.
AB  - Importance: Posttraumatic stress disorder (PTSD) is associated with an increased
      risk of type 2 diabetes mellitus (T2DM). Existing literature has adjusted for
      obesity in combination with other confounders, which does not allow estimating
      the contribution of obesity alone on the association of PTSD with incident T2DM.
      Objective: The current study was designed to determine if obesity accounted for
      the association between PTSD and incident T2DM. Design, Setting, and
      Participants: This cohort study used data from Veterans Health Administration
      medical records collected from patients with PTSD and without PTSD from 2008 to
      2015. Patients were eligible for study inclusion if they were free of prevalent
      PTSD and T2DM for 12 months prior to index date. To estimate whether the
      association of PTSD and incident T2DM remained independent of obesity, Cox
      proportional hazard models were computed before and after adding obesity to the
      model and then further expanded by adding psychiatric disorders, psychotropic
      medications, physical conditions, smoking status, and demographics. Additional
      Cox models were computed to compare the risk of incident T2DM in patients with
      PTSD with and without obesity. Data analysis was completed from February 2018 to
      May 2018. Exposures: Two International Classification of Diseases, Ninth Revision
      (ICD-9) codes for PTSD in the same 12 months and obesity, defined by a body mass
      index of 30 or more or an ICD-9 code for obesity. Main Outcomes and Measures:
      Incident T2DM, as defined by ICD-9 codes. Results: Among 2204 patients without
      PTSD, the mean (SD) age was 47.7 (14.3) years; 1860 (84.4%) were men, 1426
      (64.7%) were white, and 956 (43.4%) were married. Among 3450 patients with PTSD,
      the mean (SD) age was 42.8 (14.2) years; 2983 (86.5%) were men, 2238 (64.9%) were
      white, and 1525 (44.2%) were married. The age-adjusted association between PTSD
      and incident T2DM was significant (hazard ratio [HR], 1.33 [95% CI, 1.08-1.64]; P
      = .01), and after adding obesity to the model, this association was reduced and
      no longer significant (HR, 1.16 [95% CI, 0.94-1.43]; P = .18). Results of the
      full model, which included additional covariate adjustment, revealed no
      association between PTSD and incident T2DM (HR, 0.84 [95% CI, 0.64-1.10]; P =
      .19). Among patients with PTSD with obesity, the age-adjusted incidence of T2DM
      was 21.0 per 1000 person-years vs 5.8 per 1000 person-years in patients without
      obesity. In patients without PTSD, it was 21.2 per 1000 person-years for patients
      with obesity vs 6.4 per 1000 person-years in those without obesity. Conclusions
      and Relevance: In this study of patients who use the Veterans Health
      Administration for health care, obesity moderated the association between PTSD
      and incident T2DM. The incidence of T2DM in patients with PTSD who are not obese
      is similar to the national incidence rate in the United States. These results
      suggest PTSD is not likely to have a causal association with incident T2DM.
      Future research is needed to determine if PTSD remission can lead to weight loss
      and reduced T2DM incidence.

PMID- 30090921
TI  - A White Patch on the Tongue.

PMID- 30090922
TI  - Depth of Propofol Sedation and Postoperative Delirium: The Jury Is Still Out.

PMID- 30090923
TI  - Effect of Depth of Sedation in Older Patients Undergoing Hip Fracture Repair on
      Postoperative Delirium: The STRIDE Randomized Clinical Trial.
AB  - Importance: Postoperative delirium is the most common complication following
      major surgery in older patients. Intraoperative sedation levels are a possible
      modifiable risk factor for postoperative delirium. Objective: To determine
      whether limiting sedation levels during spinal anesthesia reduces incident
      delirium overall. Design, Setting, and Participants: This double-blind randomized
      clinical trial (A Strategy to Reduce the Incidence of Postoperative Delirum in
      Elderly Patients [STRIDE]) was conducted from November 18, 2011, to May 19, 2016,
      at a single academic medical center and included a consecutive sample of older
      patients (>=65 years) who were undergoing nonelective hip fracture repair with
      spinal anesthesia and propofol sedation. Patients were excluded for preoperative
      delirium or severe dementia. Of 538 hip fractures screened, 225 patients (41.8%)
      were eligible, 10 (1.9%) declined participation, 15 (2.8%) became ineligible
      between the time of consent and surgery, and 200 (37.2%) were randomized. The
      follow-up included postoperative days 1 to 5 or until hospital discharge.
      Interventions: Heavier (modified observer's assessment of sedation score of 0-2)
      or lighter (observer's assessment of sedation score of 3-5) propofol sedation
      levels intraoperatively. Main Outcomes and Measures: Delirium on postoperative
      days 1 to 5 or until hospital discharge determined via consensus panel using
      Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text
      Revision) criteria. The incidence of delirium was compared between intervention
      groups with and without stratification by the Charlson comorbidity index (CCI).
      Results: Of 200 participants, the mean (SD) age was 82 (8) years, 146 (73%) were
      women, 194 (97%) were white, and the mean (SD) CCI was 1.5 (1.8). One hundred
      participants each were randomized to receive lighter sedation levels or heavier
      sedation levels. A good separation of intraoperative sedation levels was
      confirmed by multiple indices. The overall incident delirium risk was 36.5% (n =
      73) and 39% (n = 39) vs 34% (n = 34) in heavier and lighter sedation groups,
      respectively (P = .46). Intention-to-treat analyses indicated no statistically
      significant difference between groups in the risk of incident delirium (log-rank
      test chi2, 0.46; P = .46). However, in a prespecified subgroup analysis, when
      stratified by CCI, sedation levels did effect the delirium risk (P for
      interaction = .04); in low comorbid states (CCI = 0), heavier vs lighter sedation
      levels doubled the risk of delirium (hazard ratio, 2.3; 95% CI, 1.1- 4.9). The
      level of sedation did not affect delirium risk with a CCI of more than 0.
      Conclusions and Relevance: In the primary analysis, limiting the level of
      sedation provided no significant benefit in reducing incident delirium. However,
      in a prespecified subgroup analysis, lighter sedation levels benefitted reducing
      postoperative delirium for persons with a CCI of 0. Trial Registration:
      clinicaltrials.gov Identifier: NCT00590707.

PMID- 30090924
TI  - A Visit to the Emergency Department With Neck and Shoulder Pain.

PMID- 30090925
TI  - Addressing Barriers to Inclusion of Pregnant Women in Clinical Trials.

PMID- 30090926
TI  - New Editorial Board Member-July 2018.

PMID- 30090927
TI  - Suicide and Physician-Assisted Death for Persons With Psychiatric Disorders: How
      Much Overlap?

PMID- 30090928
TI  - Association of Parent and Offspring Religiosity With Offspring Suicide Ideation
      and Attempts.
AB  - Importance: Previous studies have shown an inverse association between offspring
      religiosity and suicidal ideation/attempts, but the association of parent
      religiosity on offspring suicidal ideation/attempts has not been examined.
      Objective: To examine associations of parent and offspring religiosity with
      suicide ideation and attempts in offspring. Design, Setting, and Participants:
      The study is based on offspring (generation 3) from a 3-generation family study
      at New York State Psychiatric Institute and Columbia University, in which
      generations 2 and 3 were defined as being at high risk or low risk for major
      depressive disorder because of the presence or absence of major depressive
      disorder in generation 1. The association between suicidal behaviors
      (ideation/attempts) and parent and offspring religiosity in generation 3
      offspring aged 6 to 18 years (214 offspring from 112 nuclear families) was
      examined. Main Outcomes and Measures: Parents' psychiatric diagnoses and suicidal
      behaviors were assessed with the Schedule for Affective Disorders and
      Schizophrenia, and offspring were independently assessed using the child version.
      Two measures of religiosity were assessed: religious importance and religious
      attendance. Logistic regressions in the framework of generalized estimation
      equations were performed to analyze offspring suicidal behaviors while adjusting
      for sibling correlation and offspring age, sex, and familial depression risk
      status. Results: Of 214 offspring, 112 (52.3%) were girls. Offspring religious
      importance was associated with a lower risk for suicidal behavior in girls (odds
      ratio [OR], 0.48; 95% CI, 0.33-0.70) but not in boys (OR, 1.15; 95% CI, 0.74
      1.80) (religiosity by sex interaction, P = .05). Religious attendance was
      associated with a lower risk for suicidal behavior in girls (OR, 0.64; 95% CI,
      0.49-0.84) but not boys (OR, 0.94; 95% CI, 0.69-1.27) (religiosity by sex
      interaction, P = .17). Parent religious importance was associated with a lower
      risk for offspring suicidal behavior (OR, 0.61; 95% CI, 0.41-0.91) but not parent
      religious attendance. When parent and offspring religious importance were
      considered simultaneously, we found a lower risk associated with parental
      religious importance (OR, 0.61; 95% CI, 0.39-0.96) independent of offspring
      importance. These associations were independent of parental depression, marital
      status, and parental suicide ideation. Conclusions and Relevance: In this study,
      parental belief in religious importance was associated with lower risk for
      suicidal behavior in offspring independent of an offspring's own belief about
      religious importance and other known parental factors, such as parental
      depression, suicidal behavior, and divorce.

PMID- 30090929
TI  - Association of Immunologic Markers With Survival in Upfront Resectable Pancreatic
      Cancer.

PMID- 30090930
TI  - Randomized Trial Needed to Confirm Whether Dalcetrapib Improves Outcomes for
      Specific ADCY9 Genotype-Reply.

PMID- 30090931
TI  - Association of Bullous Pemphigoid With Dipeptidyl-Peptidase 4 Inhibitors in
      Patients With Diabetes: Estimating the Risk of the New Agents and Characterizing
      the Patients.
AB  - Importance: The association of bullous pemphigoid (BP) with the use of dipeptidyl
      peptidase 4 (DPP-4) inhibitors among patients with diabetes has recently emerged.
      The risk of developing BP during treatment with new DPP-4 inhibitor agents like
      linagliptin is yet to be established. The clinical features and the prognostic
      outcomes of patients with DPP-4 inhibitor-associated BP are yet to be
      established. Objectives: Primarily to estimate the association between DPP-4
      inhibitor exposure and the development of BP, and secondarily to characterize the
      clinical features and history of patients with DPP-4 inhibitor-associated BP.
      Design, Setting, and Participants: A retrospective case-control study of the
      intake of different DPP-4 inhibitor agents and metformin and occurrence of BP
      among patients with diabetes in a tertiary care referral center for autoimmune
      bullous diseases in northern Israel. Included were 82 consecutive patients with
      diabetes and immunopathologically validated BP diagnosed between January 1, 2011,
      and December 31, 2017, and 328 age-, sex-, and ethnicity-matched control
      participants with diabetes but without BP. Main Outcomes and Measures: Patients
      with diabetes and BP and exposure to DPP-4 inhibitors were followed up for a
      median of 2.0 years and compared with other patients with diabetes and BP who
      were not exposed to DPP-4 inhibitors regarding clinical and immunological
      features, laboratory analyses, treatments, and clinical outcomes. Results: Eighty
      two patients with BP and 328 age- and sex-matched control participants were
      enrolled; mean (SD) age, 79.1 (9.1) years; and 44 patients were female (53.7%).
      Overall, DPP-4 inhibitor intake was associated with a 3-fold increased risk for
      BP (adjusted odds ratio [OR], 3.2; 95% CI, 1.9-5.4). The adjusted ORs for
      vildagliptin and linagliptin were 10.7 (95% CI, 5.1-22.4) and 6.7 (95% CI, 2.2
      19.7), respectively. The association of DPP-4 inhibitor use with BP was
      independent of the use of metformin and was stronger among male (OR, 4.46; 95%
      CI, 2.11-9.40) than female (OR, 1.88; 95%, CI 0.92-3.86) patients and strongest
      in patients younger than 70 years (OR, 5.59; 95% CI, 1.73-18.01). Patients with
      DPP-4 inhibitor-associated BP presented with higher mucosal involvement (22.2% vs
      6.5%; P = .04) and lower mean (SD) peripheral eosinophil counts (399.8 [508.0] vs
      1117.6 [1847.6] cells/MUL; P = .01) than those with BP who had not been exposed
      to DPP-4 inhibitor. Discontinuation of DPP-4 inhibitor treatment was followed by
      improved clinical outcomes. Conclusions and Relevance: Vildagliptin and, to a
      lesser extent, linagliptin are associated with an increased risk of BP. This may
      partly explain the increasing incidence of BP in Israel. Discontinuation of DPP-4
      inhibitor treatment in patients with diabetes should be considered when BP is
      diagnosed.

PMID- 30090932
TI  - Associations of Circulating Extracellular RNAs With Myocardial Remodeling and
      Heart Failure.
AB  - Importance: Mortality is high among patients heart failure (HF) who are receiving
      treatment, and therefore identifying new pathways rooted in preclinical cardiac
      remodeling phenotypes may afford novel biomarkers and therapeutic avenues.
      Circulating extracellular RNAs (ex-RNAs) are an emerging class of biomarkers with
      target-organ epigenetic effects relevant to myocardial biology, although large
      human investigations remain limited. Objective: To measure the association of
      highly expressed circulating ex-RNAs with left ventricular remodeling and
      incident HF in a community-based cohort. Design, Setting, and Participants: This
      is a prospective observational cohort study of individuals who were included in
      the eighth examination of the Framingham Offspring Cohort (2005-2008). Collected
      data include measurements of the left ventricle via electrocardiography,
      determination of circulating ex-RNAs in plasma, and incidence of heart failure.
      Data analysis was completed from December 2016 to June 2018. Exposures: A total
      of 398 circulating ex-RNA molecules in plasma were measured by reverse
      transcription polymerase chain reaction; disease ontology analysis was also
      performed. Main Outcomes and Measures: Echocardiographic indices of left
      ventricular (LV) remodeling and incident heart failure. Results: A total of 2763
      participants of the Framingham Heart Study with measured ex-RNAs (mean [SD] age,
      66.3 [9.0] years; 1499 [54.3%] female) were included in this study. Of this
      sample, 2429 to 2432 individuals had echocardiographic measures recorded
      (depending on the measurement). A total of 2681 individuals had HF status
      determined, of whom 116 (4.3%) experienced HF (median [interquartile range]
      follow-up, 7.7 [6.6-8.6] years). We identified 12 ex-RNAs associated with LV mass
      and at least 1 other echocardiographic phenotype (LV end-diastolic volume or left
      atrial dimension). Of these 12 ex-RNAs, 3 micro RNAs (miR-17, miR-20a, and miR
      106b) were associated with a 15% reduction in long-term incident HF per 2-fold
      increase in circulating level during the follow-up period, after adjustments for
      age, sex, established HF risk factors, and prevalent or interim myocardial
      infarction. These 3 RNAs shared sequence homology and targeted a shared group of
      messenger RNAs that specified pathways relevant to HF (eg, transforming growth
      factor-beta signaling, growth/cell cycle, and apoptosis), and shared a disease
      association with hypertension in disease ontology analysis. Conclusions and
      Relevance: This study identifies a group of circulating, noncoding RNAs
      associated with echocardiographic phenotypes, long-term incident HF, and pathways
      relevant to myocardial remodeling in a large community-based sample. Further
      investigations into the functional biology of these ex-RNAs are warranted for
      surveillance for HF prevention.

PMID- 30090934
TI  - Risk Factors Associated With Perioperative Complications and Prolonged Length of
      Stay After Laparoscopic Adrenalectomy.
AB  - Importance: Laparoscopic adrenalectomy is the gold standard for most adrenal
      disorders and its frequency in the United States is increasing. While national
      and administrative databases can adjust for patient factors, comorbidities, and
      institutional variations, granular disease-specific data that may significantly
      influence the incidence of perioperative complications and length of stay (LOS)
      are lacking. Objective: To investigate factors associated with perioperative
      complications and LOS after laparoscopic adrenalectomy. Design, Setting, and
      Participants: This cohort study was carried out at a single academic medical
      center, with all patients who underwent laparoscopic adrenalectomy between 1993
      and 2017 by the endocrine surgery department. Multivariable linear and logistic
      regression were used to obtain adjusted odds ratios (ORs). Main Outcomes and
      Measures: The primary outcome was perioperative complications with a Dindo
      Clavien grade of 2 or more. The secondary outcome was prolonged length of stay,
      defined as a stay longer than the 75th percentile of the overall cohort. Results:
      We identified 640 patients who underwent 653 laparoscopic adrenalectomies, of
      whom 370 (56.7%) were female. The median age was 51 (range, 5-88) years. A total
      of 76 complications with a Dindo-Clavien grade of 2 or more occurred in 55
      patients (8.4%), with postoperative mortality in 2 patients (0.3%). The median
      hospital length of stay was 1 day (range, 0-32 days). Factors independently
      associated with increased complications were American Society of
      Anesthesiologists class 3 or 4 (OR, 2.78 [95% CI, 1.39-5.55]; P < .01), diabetes
      (OR, 2.39 [95% CI, 1.14-5.01]; P = .02), conversion to hand-assisted or open
      surgery (OR, 5.32 [95% CI, 1.84-15.41]; P < .01), a diagnosis of pheochromocytoma
      (OR, 4.31 [95% CI, 1.43-13.05]; P = .01), and a tumor size of 6 cm or greater
      (OR, 2.47 [95% CI, 1.05-5.78]; P = .04). Prolonged length of stay was associated
      with age 65 years or older (OR, 2.44 [95% CI, 1.31-4.57]; P = .01), an American
      Society of Anesthesiologists class 3 or 4 (OR, 3.48 [95% CI, 1.88-6.41]; P <
      .01), any procedural conversion (OR, 63.28 [95% CI, 12.53-319.59]; P < .01), and
      a tumor size of 4 cm or larger (4-6 cm: OR, 2.38 [95% CI, 1.21-4.67]; P = .01;
      >=6 cm: OR, 2.46 [95% CI, 1.12-5.40]; P = .03). Conclusions and Relevance:
      Laparoscopic adrenalectomy remains safe for most adrenal disorders. Patient
      comorbidities, adrenal pathology, and tumor size are associated with the risk of
      complications and length of stay and should all be considered in selecting and
      preparing patients for surgery.

PMID- 30090935
TI  - Topical Crisaborole-A Potential Treatment for Recalcitrant Palmoplantar
      Psoriasis.

PMID- 30090936
TI  - Avoiding and Managing Medicare Fraud and Abuse Investigations of Mohs Surgery:
      Mohs in the Crosshairs.

PMID- 30090937
TI  - National Surgical, Obstetric, and Anesthesia Planning in the Context of Global
      Surgery: The Way Forward.

PMID- 30090938
TI  - Laparoscopic Transabdominal Adrenalectomy-A Procedure That Has Stood the Test of
      Time.

PMID- 30090939
TI  - Can Acupuncture Keep Women on Their Breast Cancer Drugs?

PMID- 30090941
TI  - Distinguishing Mild, Moderate, and Severe Hidradenitis Suppurativa-Reply.

PMID- 30090943
TI  - The Father of Spanish Dermatology.

PMID- 30090940
TI  - Association of Interleukin 6 Receptor Variant With Cardiovascular Disease Effects
      of Interleukin 6 Receptor Blocking Therapy: A Phenome-Wide Association Study.
AB  - Importance: Electronic health record (EHR) biobanks containing clinical and
      genomic data on large numbers of individuals have great potential to inform drug
      discovery. Individuals with interleukin 6 receptor (IL6R) single-nucleotide
      polymorphisms (SNPs) who are not receiving IL6R blocking therapy have biomarker
      profiles similar to those treated with IL6R blockers. This gene-drug pair
      provides an example to test whether associations of IL6R SNPs with a broad range
      of phenotypes can inform which diseases may benefit from treatment with IL6R
      blockade. Objective: To determine whether screening for clinical associations
      with the IL6R SNP in a phenome-wide association study (PheWAS) using EHR biobank
      data can identify drug effects from IL6R clinical trials. Design, Setting, and
      Participants: Diagnosis codes and routine laboratory measurements were extracted
      from the VA Million Veteran Program (MVP); diagnosis codes were mapped to
      phenotype groups using published PheWAS methods. A PheWAS was performed by
      fitting logistic regression models for testing associations of the IL6R SNPs with
      1342 phenotype groups and by fitting linear regression models for testing
      associations of the IL6R SNP with 26 routine laboratory measurements.
      Significance was reported using a false discovery rate of 0.05 or less. Findings
      were replicated in 2 independent cohorts using UK Biobank and Vanderbilt
      University Biobank data. The Million Veteran Program included 332 799 US
      veterans; the UK Biobank, 408 455 individuals from the general population of the
      United Kingdom; and the Vanderbilt University Biobank, 13 835 patients from a
      tertiary care center. Exposures: IL6R SNPs (rs2228145; rs4129267). Main Outcomes
      and Measures: Phenotypes defined by International Classification of Diseases,
      Ninth Revision codes. Results: Of the 332 799 veterans included in the main
      cohort, 305 228 (91.7%) were men, and the mean (SD) age was 66.1 (13.6) years.
      The IL6R SNP was most strongly associated with a reduced risk of aortic aneurysm
      phenotypes (odds ratio, 0.87-0.90; 95% CI, 0.84-0.93) in the MVP. We observed
      known off-target effects of IL6R blockade from clinical trials (eg, higher
      hemoglobin level). The reduced risk for aortic aneurysms among those with the
      IL6R SNP in the MVP was replicated in the Vanderbilt University Biobank, and the
      reduced risk for coronary heart disease was replicated in the UK Biobank.
      Conclusions and Relevance: In this proof-of-concept study, we demonstrated
      application of the PheWAS using large EHR biobanks to inform drug effects. The
      findings of an association of the IL6R SNP with reduced risk for aortic aneurysms
      correspond with the newest indication for IL6R blockade, giant cell arteritis, of
      which a major complication is aortic aneurysm.

PMID- 30090944
TI  - Friedrich Daniel von Recklinghausen.

PMID- 30090946
TI  - Error in Methods Section.

PMID- 30090947
TI  - Changes in the Synchrony of Multimodal Communication in Early Language
      Development.
AB  - Purpose: The aim of this study is to analyze the changes in temporal synchrony
      between gesture and speech of multimodal communicative behaviors in the
      transition from babbling to two-word productions. Method: Ten Spanish-speaking
      children were observed at 9, 12, 15, and 18 months of age in a semistructured
      play situation. We longitudinally analyzed the synchrony between gestures and
      vocal productions and between their prominent parts. We also explored the
      relationship between gestural-vocal synchrony and independent measures of
      language development. Results: Results showed that multimodal communicative
      behaviors tend to be shorter with age, with an increasing overlap of its
      constituting elements. The same pattern is found when considering the synchrony
      between the prominent parts. The proportion of overlap between gestural and vocal
      elements at 15 months of age as well as the proportion of the stroke overlapped
      with vocalization appear to be related to lexical development 3 months later.
      Conclusions: These results suggest that children produce gestures and
      vocalizations as coordinated elements of a single communication system before the
      transition to the two-word stage. This coordination is related to subsequent
      lexical development in this period. Supplemental Material:
      https://doi.org/10.23641/asha.6912242.

PMID- 30090948
TI  - Interferon gamma decreases intestinal epithelial aquaporin 3 expression through
      downregulation of constitutive transcription.
AB  - : Aquaporin (AQP) 3 expression is altered in inflammatory bowel diseases,
      although the exact mechanisms regulating AQP abundance are unclear. Although
      interferon gamma (IFNgamma) is centrally involved in intestinal inflammation, the
      effect of this cytokine on AQP3 expression remains unknown. HT-29 human colonic
      epithelial cells were treated with IFNgamma to assess AQP3 mRNA expression by
      real-time RT-PCR and functional protein expression through the uptake of
      radiolabelled glycerol. Transient knockdown of signal transducer and activator of
      transcription 1 (STAT1), STAT3, Sp1, and Sp3 were performed to determine the
      involvement of these transcription factors in the IFNgamma-induced signalling
      cascade. AQP3 promoter regions involved in the response to IFNgamma were assessed
      using a luciferase reporter system. Likewise, enteroids derived from human
      colonic biopsies were also treated with IFNgamma to assess for changes in AQP3
      mRNA expression. IFNgamma decreased AQP3 mRNA expression in HT-29 cells in a time
      and concentration-dependent manner and reduced functional AQP3 protein
      expression (decreased 3H-labelled glycerol uptake). IFNgamma also reduced AQP3
      expression in enteroids derived from human colonic biopsies. Knockdown of STAT1
      partially prevented the IFNgamma-induced downregulation of AQP3 expression,
      whereas STAT3 and Sp3 knockdowns resulted in increased baseline expression of
      AQP3 but did not alter IFNgamma-induced downregulation. Constitutive
      transcription of AQP3 is downregulated by IFNgamma as demonstrated using the
      luciferase reporter system, with Sp3 bound to the AQP3 promoter as shown by
      chromatin immunoprecipitation. AQP3 constitutive transcription in intestinal
      epithelial cells is downregulated by IFNgamma. This response requires STAT1 that
      is postulated to drive the downregulation of AQP3 expression through increased
      acetylation or decreased deacetylation the AQP3 promoter, ultimately resulting in
      decreased constitutive transcription of AQP3. KEY MESSAGES: * IFNgamma suppresses
      the expression of AQP3 in intestinal epithelial cells. * Proximal AQP3 promoter
      elements are sufficient to drive constitutive expression and mediate the IFNgamma
      induced downregulation of AQP3 mRNA expression. * IFNgamma-induced suppression of
      AQP3 is dependent upon STAT1 expression, but not STAT3, Sp1, or Sp3.

PMID- 30090949
TI  - Empagliflozin, SGLT2 inhibitor, attenuates renal fibrosis in rats exposed to
      unilateral ureteric obstruction: potential role of klotho expression.
AB  - Chronic kidney disease (CKD) is a global healthcare problem; however until now,
      there is no effective treatment that can stop its progression. In this study, we
      aimed to investigate the effect of empagliflozin, a sodium-glucose linked
      transporter-2 inhibitor (SGLT2I) in a model of unilateral ureteric obstruction
      (UUO) in rats, as a model of progressive renal interstitial fibrosis in vivo and
      the possibility of inclusion of klotho protein. Rats were randomly divided into
      five groups: group 1: control group, group 2: UUO untreated group, group 3:
      prophylactic SGLT2I treatment before UUO, group 4: immediate SGLT2I treatment
      after UUO, and group 5: delayed SGLT2I treatment (this group received distilled
      water 1 week after UUO then empagliflozin for 2 weeks). At the end of the
      experiment period, animals were sacrificed, and kidney fibrotic and inflammatory
      parameters were measured. Also kidney sections were examined histopathologically
      for CTGF expression. UUO resulted in renal dysfunction and fibrosis through
      upregulating inflammatory cascade (NF-kappaB-TLR4) as well as many fibrotic
      pathways (as TGF-beta1, alphaSMA, Wnt, CTGF, and fibronectin) with significant
      reduction in the klotho protein expression. We hypothesized that both
      prophylactic and immediate treatment with empagliflozin after UUO in rats exert
      more renoprotective effect in comparison with delayed treatment via enhancement
      of renal klotho expression and activity, for further investigations.

PMID- 30090951
TI  - ?

PMID- 30090950
TI  - [The distal radioulnar joint-an update].

PMID- 30090952
TI  - A microfluidic device for motility and osmolality analysis of zebrafish sperm.
AB  - A microfluidic chip is described that facilitates research and quality control
      analysis of zebrafish sperm which, due to its miniscule (i.e., 2-5 MUl) sample
      volume and short duration of motility (i.e., <1 min), present a challenge for
      traditional manual assessment methods. A micromixer molded in
      polydimethylsiloxane (PDMS) bonded to a glass substrate was used to activate
      sperm samples by mixing with water, initiated by the user depressing a transfer
      pipette connected to the chip. Sample flow in the microfluidic viewing chamber
      was able to be halted within 1 s, allowing for rapid analysis of the sample using
      established computer-assisted sperm analysis (CASA) methods. Zebrafish sperm cell
      activation was consistent with manual hand mixing and yielded higher values of
      motility at earlier time points, as well as more subtle time-dependent trends in
      motility, than those processed by hand. Sperm activation curves, which indicate
      sample quality by evaluating percentage and duration of motility at various
      solution osmolalities, were generated with on-chip microfabricated gold floor
      electrodes interrogated by impedance spectroscopy. The magnitude of admittance
      was linearly proportional to osmolality and was not affected by the presence of
      sperm cells in the vicinity of the electrodes. This device represents a pivotal
      step in streamlining methods for consistent, rapid assessment of sperm quality
      for aquatic species. The capability to rapidly activate sperm and consistently
      measure motility with CASA using the microfluidic device described herein will
      help improve the reproducibility of studies on sperm and assist development of
      germplasm repositories.

PMID- 30090954
TI  - Neutrophil-to-Lymphocyte Ratio in Acute Cerebral Hemorrhage: a System Review.
AB  - Spontaneous intracerebral hemorrhage (ICH) accounts for approximately 10 to 30%
      of all acute cerebrovascular events, and it is the type of stroke associated with
      the highest rates of mortality and residual disability. The inflammatory response
      is early triggered by hematoma components and can enhance the damage within the
      hemorrhagic brain. Assessment of peripheral biomarkers of inflammation could
      contribute to increase knowledge about some of the mechanisms involved in the ICH
      induced injury and yield information on the disease course. The neutrophil-to
      lymphocyte ratio (NLR) integrates information on both the innate and adaptive
      compartments of the immunity and represents a reliable measure of the
      inflammatory burden. The aim of the current review is to highlight the available
      evidence about the relationships between the NLR and clinical outcome in patients
      with acute ICH and provide critical insights into the underlying pathophysiology.
      Since no therapy targeting ICH-induced primary injury has yielded conclusive
      benefits and ICH treatment remains mainly supportive within a framework of
      general critical care management, these findings could also contribute to
      identify new potential targets for neuroprotection and develop novel therapeutic
      strategies.

PMID- 30090955
TI  - Lyme borreliosis, ticks and Borrelia species.

PMID- 30090953
TI  - Ameliorative effects of hydrogen sulfide (NaHS) on chronic kidney disease-induced
      brain dysfunction in rats: implication on role of nitric oxide (NO) signaling.
AB  - Chronic kidney disease (CKD) is a major public health problem worldwide and is
      associated with spatial learning deficits. The aim of the present study was to
      evaluate the protective effects of hydrogen sulfide (H2S) on CKD-mediated
      behavioral deficits with emphasis to the role of nitric oxide (NO) in these
      effects. Fifty rats were randomly allocated to five experimental groups
      including: sham, Five-sixth (5/6) nephrectomy (Nx), 5/6Nx + NaHS, 5/6Nx + NaHS+L
      nitroarginine methyl ester (L-NAME), and 5/6Nx + NaHS+aminoguanidine (AMG).
      Twelve weeks after 5/6Nx, we evaluated proteinuria, creatinine clearance (CrCl),
      oxidative/antioxidant status, and hippocampus neuro-inflammation and NO synthase
      genes in all groups. Furthermore, training trials of all animals were conducted
      in the Morris water maze (MWM) task one day before animal euthanizing. As
      predicted, 5/6Nx induced several injuries, including enhancement of proteinuria
      and reduction of CCr, oxidant/antioxidant imbalance and up-regulation of TNF
      alpha and IL-1beta gene expressions in the hippocampus tissues. As predicted,
      5/6Nx resulted in learning and memory impairments, and increased escape latency
      during acquisition trials in the MWM task. Interestingly, NaHS (H2S donor)
      improved behavioral deficits, renal dysfunction, accelerated anti-oxidant/anti
      inflammatory responses and increased eNOS and decreased iNOS. Moreover, these
      effects of NaHS were prevented by L-NAME but not AMG co-administration. In
      conclusion, H2S ameliorates CKD-mediated brain dysfunctions, through interaction
      with NO signaling in the hippocampus.

PMID- 30090958
TI  - [Thoracoabominal aortic aneurysms-endovascular options].
AB  - BACKGROUND: Thoracoabdominal aortic aneurysms (TAAA) are predominantly
      atherosclerotic related and are usually asymptomatic. Treatment is necessary from
      a size greater 6.5 cm, while patients with rapidly growing, compression of organ
      structures, aneurysm-related connecting tissue orders must be treated from a
      diameter of 6 cm. METHODS: Elective interventions may be performed with
      fenestrated and/or branched grafts. Another possibility is the chimney, sandwich
      or periscop technique for treating TAAA. Depending on the extension of the TAAA,
      implantation of tube grafts for the thoracic aorta or bifurcation grafts for the
      abdominal aorta is necessary. Symptomatic TAAA may be treated by implantation of
      a t-Branch(r) or using the chimney, sandwich or periscop technique. CONCLUSIONS:
      The preinterventional planning and sizing with the help of computed tomography
      (CT) scans for endovascular repair of TAAA, and the implantation of the grafts
      during the procedure are challenging; thus, a well-experienced interdisciplinary
      team of medical and nonmedical specialists is required.

PMID- 30090959
TI  - [Ultrasound of the elbow-standard examination technique and normal anatomy].
AB  - CLINICAL/METHODICAL ISSUE: Ultrasound of the elbow facilitates easily accessible
      evaluation of different pathologic conditions. The background for evaluating any
      pathologic state is the well-grounded knowledge of normal anatomy and standard
      ultrasound technique. STANDARD RADIOLOGICAL METHODS/METHODICAL
      INNOVATIONS/PERFORMANCE: A unique feature of ultrasound compared to other imaging
      modalities of the elbow is the possibility of dynamic imaging, the examination of
      the patient at the bedside and the direct assessment of the contralateral side as
      a reference. AIM: The aim of this article is to present standard ultrasound
      technique in examining the elbow. A four-quadrant model of the elbow is used and
      the recommendations of the DEGUM (German Society of Ultrasound in Medicine) and
      ESSR (European Society of Musculoskeletal Radiology) are followed.

PMID- 30090960
TI  - Assisted reproduction techniques and prenatal diagnosis of Beckwith-Wiedemann
      spectrum presenting with omphalocele.

PMID- 30090961
TI  - Phenotyping normal kidney function in elderly patients with type 2 diabetes: a
      cross-sectional multicentre study.
AB  - AIMS: Type 2 diabetes (T2D) accelerates the decline in glomerular function;
      however, some individuals do not develop chronic kidney disease despite advanced
      age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80 years
      or older who presented with a fully preserved kidney function. METHODS: From an
      Italian population of 281,217 T2D outpatients, we collected data on demographics,
      anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver
      enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate
      (AER), chronic complications, and medication use. We primarily compared patients
      with a fully preserved kidney function (eGFR > 90 ml/min/1.73 m2 and AER < 30
      mg/24 h, or G1A1) with those with mild kidney impairment (eGFR 60-90 ml/min/1.73
      m2 and AER < 30 mg/24 h, or G2A1). RESULTS: N = 113,860 had available data for
      eGFR and AER, 21,648 of whom were aged >= 80. G1A1 (n = 278) and G2A1 (n = 6647)
      patients represented 1.3 and 30.7% of aged T2D patients, respectively, with an
      average diabetes duration of 16 years. Differences between the G1A1 and G2A1
      groups were entered in a multiple logistic regression analysis with and without
      imputation of missing data. After adjustment and in both imputed and non-imputed
      datasets, younger age, lower BMI and lower triglycerides were associated with
      fully preserved versus mildly impaired kidney function. The comparison between
      G1A1 and G1A2/3 yielded different results. CONCLUSIONS: In a rare population of
      patients with a fully preserved kidney function despite old age and long-lasting
      diabetes, lower BMI and triglycerides suggest that protection from lipotoxicity
      may preserve kidney function over time.

PMID- 30090962
TI  - Protective immunity elicited by measles vaccine exerts anti-tumor effects on
      measles virus hemagglutinin gene-modified cancer cells in a mouse model.
AB  - PURPOSE: Measles vaccine is widely used in China to prevent the measles virus
      (MV) infection. People immunized with measles vaccine can obtain long-term
      protective immunity. Measles virus surface glycoprotein hemagglutinin (H) can
      also induce MV-specific immune responses. However, little is known about whether
      the existence of the protective immune system against MV in the host can exert
      anti-tumor effects and whether the MV-H gene can serve as a therapeutic gene.
      METHODS: We first vaccinated mice with measles vaccine, then inoculated them with
      MV-H protein-expressing tumor cells and observed the rate of tumor formation. We
      also treated mice with H protein-expressing tumor cells with measles vaccine and
      assessed tumor size and overall survival. RESULTS: Active vaccination using
      measles vaccine not only protected mice from developing tumors, but also
      eradicated established tumors. Measles vaccine elicited H-specific IFN-gamma, TNF
      alpha and granzyme B-producing CD8+ T cells and increased cytotoxic T lymphocyte
      (CTL) activity specific for H antigen, which provided a strong therapeutic
      benefit against H protein-expressing tumors. In addition, measles vaccine
      decreased the population of myeloid-derived suppressor cells (MDSCs) and
      regulatory T cells (Tregs). CONCLUSIONS: Our study demonstrated that tumor cells
      expressing H protein could activate the immune memory response against MV, which
      exerted specific anti-tumor effects, and indicated that the MV-H gene can be used
      as a potential therapeutic gene for cancer gene therapy.

PMID- 30090963
TI  - Percutaneous transluminal plasty: a novel approach for refractory anastomotic
      stricture after esophagectomy.
AB  - Anastomotic stricture is often observed after esophagectomy. Surgical treatment
      is considered for refractory stricture to conservative treatments. However, it is
      not established what type of surgery is safe and effective. In this report, we
      present a novel approach, percutaneous transluminal plasty, for refractory
      anastomotic stricture reconstructed via the subcutaneous route in esophagectomy.
      We believe that the effectiveness and safety of this technique is considerably
      good and can become a good alternative for refractory stricture after
      esophagectomy.

PMID- 30090964
TI  - Isolation, characterization and efficacy of phage MJ2 against biofilm forming
      multi-drug resistant Enterobacter cloacae.
AB  - Biofilm is involved in a variety of infections, playing a critical role in the
      chronicity of infections. Enterobacter cloacae is a biofilm-forming and multi
      drug-resistant (MDR) nosocomial pathogen leading to significant morbidity and
      mortality. This study aimed at isolation of a bacteriophage against MDR clinical
      strain of E. cloacae and its efficacy against bacterial planktonic cells and
      biofilm. A bacteriophage MJ2 was successfully isolated from wastewater and was
      characterized. The phage exhibited a wide range of thermal and pH stability and
      demonstrated considerable adsorption to host bacteria in the presence of CaCl2 or
      MgCl2. Transmission electron microscopy (TEM) showed MJ2 head as approximately 62
      and 54 nm width and length, respectively. It had a short non-contractile tail and
      was characterized as a member of the family Podoviridae [order Caudovirales]. The
      phage MJ2 was found to possess 11 structural proteins (12-150 kDa) and a double
      stranded DNA genome with an approximate size of 40 kb. The log-phase growth of E.
      cloacae both in biofilm and suspension was significantly reduced by the phage.
      The E. cloacae biofilm was formed under different conditions to evaluate the
      efficacy of MJ2 phage. Variable reduction pattern of E. cloacae biofilm was
      observed while treating it for 4 h with MJ2, i.e., biofilm under static
      conditions. The renewed media with intervals of 24, 72, and 120 h showed biomass
      decline of 2.8-, 3-, and 3.5-log, respectively. Whereas, the bacterial biofilm
      formed with dynamic conditions with refreshing media after 24, 72, and 120 h
      demonstrated decline in growth at 2.5-, 2.6-, and 3.3-log, respectively. It was,
      therefore, concluded that phage MJ2 possessed considerable inhibitory effects on
      MDR E. cloacae both in planktonic and biofilm forms.

PMID- 30090965
TI  - First-in-human study of 177Lu-EB-PSMA-617 in patients with metastatic castration
      resistant prostate cancer.
AB  - PURPOSE: This translational study is designed to assess the safety, dosimetry and
      therapeutic response to a single, low-dose of 177Lu-EB-PSMA-617 in comparison to
      177Lu-PSMA-617 in patients with mCRPC. METHODS: Following institutional review
      board approval and informed consent, nine patients with mCRPC were recruited.
      Four patients accepted intravenous injection of 0.80-1.1 GBq (21.5-30 mCi) of
      177Lu-EB-PSMA-617, then underwent serial whole-body planar and SPECT/CT imaging
      at 2, 24, 72, 120 and 168 h. The other five patients accepted intravenous
      injection of 1.30-1.42 GBq (35-38.4 mCi) 177Lu-PSMA-617, then underwent the same
      imaging procedures at 0.5, 2, 24, 48, and 72 h. All patients were evaluated by
      68Ga-PSMA-617 PET/CT before and one month after the treatment. Dosimetry
      evaluation was compared in both patient groups. RESULTS: When the bone metastasis
      tumors with comparable baseline SUVmax in the range of 10.0-15.0 were selected
      from the two groups for comparison, the accumulated radioactivity of 177Lu-EB
      PSMA-617 was about 3.02-fold higher than that of 177Lu-PSMA-617. Imaging dose of
      177Lu-EB-PSMA-617 treatment showed significant decrease of 68Ga-PSMA-617 uptake
      within a month, which was not observed in patients imaged with 177Lu-PSMA-617
      (SUV change: -32.43 +/- 0.14% vs. 0.21 +/- 0.37%; P = 0.002). 177Lu-EB-PSMA-617
      also had higher absorbed doses in the red bone marrow and kidneys than 177Lu-PSMA
      617 (0.0547 +/- 0.0062 vs. 0.0084 +/- 0.0057 mSv/MBq for red bone marrow, P <
      0.01; 2.39 +/- 0.69 vs. 0.39 +/- 0.06 mSv/MBq for kidneys, P < 0.01). CONCLUSION:
      This first-in-human study demonstrated that 177Lu-EB-PSMA-617 had higher
      accumulation in mCRPC and that low imaging dose appears to be effective in
      treating tumors with high 68Ga-PSMA-617 uptakes. Elevated uptakes of 177Lu-EB
      PSMA-617 in kidneys and red bone marrow were well tolerated at the administered
      low dose. Further investigations with increased dose and frequency of
      administration are warranted.

PMID- 30090966
TI  - Disease-related patterns of in vivo pathology in Corticobasal syndrome.
AB  - PURPOSE: To assess disease-related patterns of in vivo pathology in 11 patients
      with Corticobasal Syndrome (CBS) compared to 20 healthy controls and 33 mild
      cognitive impairment (MCI) patients due to Alzheimer's disease. METHODS: We
      assessed tau aggregates with [18F]AV1451 PET, amyloid-beta depositions with
      [18F]AV45 PET, and volumetric microstructural changes with MRI. We validated for
      [18F]AV1451 standardised uptake value ratio (SUVRs) against input functions from
      arterial metabolites and found that SUVRs and arterial-derived distribution
      volume ratio (DVRs) provide equally robust measures of [18F]AV1451 binding.
      RESULTS: CBS patients showed increases in [18F]AV1451 SUVRs in parietal (P <
      0.05) and frontal (P < 0.05) cortices in the affected hemisphere compared to
      healthy controls and in precentral (P = 0.008) and postcentral (P = 0.034) gyrus
      in the affected hemisphere compared to MCI patients. Our data were confirmed at
      the histopathological level in one CBS patient who underwent brain biopsy and
      showed sparse tau pathology in the parietal cortex co-localizing with increased
      [18F]AV1451 signal. Cortical and subcortical [18F]AV45 uptake was within normal
      levels in CBS patients. In parietal and frontal cortices of the most affected
      hemisphere we found also grey matter loss (P < 0.05), increased mean diffusivity
      (P < 0.05) and decreased fractional anisotropy (P < 0.05) in CBS patients
      compared to healthy controls and MCI patients. Grey matter loss and white matter
      changes in the precentral gyrus of CBS patients were associated with worse motor
      symptoms. CONCLUSIONS: Our findings demonstrate disease-related patterns of in
      vivo tau and microstructural pathology in the absence of amyloid-beta, which
      distinguish CBS from non-affected individuals and MCI patients.

PMID- 30090967
TI  - Clinical outcomes following surgical treatment of peri-implantitis at grafted and
      non-grafted implant sites: a retrospective analysis.
AB  - BACKGROUND: This retrospective analysis aimed at comparing the clinical outcomes
      following combined surgical therapy of peri-implantitis at initially grafted and
      non-grafted (i.e., pristine) implant sites. METHODS: A total of 39 patients
      exhibiting 57 implants diagnosed with peri-implantitis (i.e., 16 implants at
      grafted and 41 implants at non-grafted sites) were included. Each subject had
      received a combined (i.e., implantoplasty and augmentative therapy) surgical
      treatment procedures at respective implants (grafted sites: 10 patients, 16
      implants, non-grafted sites: 29 patients, 41 implants). A chi-squared test (chi2)
      was used to assess whether the initial grafting procedure did affect the
      treatment outcomes (i.e., disease resolution, bleeding on probing (BOP), probing
      pocket depths (PD)). The mean follow-up period was 41.9 +/- 34.75 months.
      RESULTS: At the patient level, disease resolution (i.e., absence of BOP and PD >=
      6 mm) was obtained in 4/10 (40%) at grafted and in 7/27 (24.1%) at non-grafted
      implant sites (p = 0.579). BOP reductions was found to be 60.64 +/- 40.81% at non
      grafted and 77.45 +/- 30.92% at grafted sites (p = 0.778). PD reductions amounted
      to 2.20 +/- 2.22 mm at non-grafted and 1.57 +/- 1.54 mm at grafted sites (p =
      0.969). CONCLUSIONS: The initial bone-grafting procedures at the implant sites
      did not influence the effectiveness of combined surgical therapy of peri
      implantitis.

PMID- 30090968
TI  - Chronic hypnotic use at 10 years-does the brand matter?
AB  - PURPOSE: Chronic use of sedative-hypnotics is very common, although not guideline
      endorsed. The incidence among new users is not well studied, and there are
      currently no recommendations favoring any specific agent. We quantified the risk
      for chronic use in first-time hypnotic users, and the association of the initial
      choice of hypnotic with later usage patterns. METHODS: We used the computerized
      database of Israel's largest healthcare provider. All 236,597 new users of
      sedative-hypnotics between the years 2000-2005 were followed for 10 years. Filled
      prescriptions in the second, fifth, and tenth years were recorded. The
      association of the first hypnotic choice (benzodiazepine/Z-drug) with chronic
      consumption was assessed using multivariate logistic regression. RESULTS: Average
      age on first use was 63.7 (SD +/- 16.4) years. 58.6% were women. Benzodiazepines
      were initiated in 154,929 (65.5%) of the cases. Benzodiazepine users were older
      and of lower socioeconomic status, compared to Z-drug users (p < 0.001). On the
      tenth year, 103,912 (66.8%) of new users claimed <= 30 DDDs of hypnotics, 3,1724
      (20.4%) were long-term users (>= 180 DDD/year), and 828 (0.5%) used excessively
      (>= 720 DDD/year). Z-drugs were associated with an increased risk of long-term
      use on the second year [17.3% vs. 12.4%, RR = 1.40 (1.37-1.43)] as well as on the
      fifth [21.9% vs. 13.9%, RR = 1.58 (1.55-1.61)] and tenth year [25.1% vs. 17.7%,
      RR = 1.42 (1.39-1.45)], p < 0.0001. Similar results were also observed for daily
      and excessive use (p < 0.001). CONCLUSIONS: One in five new users of sedative
      hypnotics will become a long-term user, but only 0.5% will become excessive
      users. Z-drugs were associated with an increased risk of chronic use.

PMID- 30090969
TI  - Stress Hyperglycemia in Patients with Tuberculosis Disease: Epidemiology and
      Clinical Implications.
AB  - PURPOSE OF REVIEW: The intersection of tuberculosis (TB) disease and type 2
      diabetes mellitus is severely hindering global efforts to reduce TB burdens.
      Diabetes increases the risk of developing TB disease and negatively impacts TB
      treatment outcomes including culture conversion time, mortality risk, and TB
      relapse. Recent evidence also indicates plausible mechanisms by which TB disease
      may influence the pathogenesis and incidence of diabetes. We review the
      epidemiology of stress hyperglycemia in patients with TB and the pathophysiologic
      responses to TB disease that are related to established mechanisms of stress
      hyperglycemia. We also consider clinical implications of stress hyperglycemia on
      TB treatment, and the role of TB disease on risk of diabetes post-TB. RECENT
      FINDINGS: Among patients with TB disease, the development of stress hyperglycemia
      may influence the clinical manifestation and treatment response of some patients
      and can complicate diabetes diagnosis. Research is needed to elucidate the
      relationship between TB disease and stress hyperglycemia and determine the extent
      to which stress hyperglycemia impacts TB treatment response. Currently, there is
      insufficient data to support clinical recommendations for glucose control among
      patients with TB disease, representing a major barrier for efforts to improve
      treatment outcomes for patients with TB and diabetes.

PMID- 30090971
TI  - Inotuzumab Ozogamicin: A Review in Relapsed/Refractory B-Cell Acute Lymphoblastic
      Leukaemia.
AB  - The intravenous CD22-directed antibody drug conjugate inotuzumab ozogamicin
      (Besponsa(r)) is approved in several countries including in the USA, EU and
      Japan, as monotherapy for the treatment of adults with relapsed/refractory B-cell
      acute lymphoblastic leukaemia (ALL). In adults with relapsed/refractory B-cell
      ALL who had received one or two prior treatment regimens, inotuzumab ozogamicin
      was associated with significantly higher rates of complete remission (including
      complete remission with incomplete haematological recovery) [CR/CRi] than
      standard therapy in the pivotal INO-VATE ALL trial. Inotuzumab ozogamicin was
      associated with significantly longer progression-free survival (PFS), duration of
      remission and higher haematopoietic stem cell transplantation (HSCT) rates than
      standard therapy. Although there was no significant between-group difference in
      overall survival duration as per the study design, the 2-year survival
      probability in the inotuzumab ozogamicin arm was twice that in the control arm.
      Inotuzumab ozogamicin had an acceptable tolerability profile. Thus, inotuzumab
      ozogamicin is an important new treatment option for patients with
      relapsed/refractory CD22-positive B-cell ALL.

PMID- 30090970
TI  - Vitamin D Deficiency has a Negative Impact on Cetuximab-Mediated Cellular
      Cytotoxicity against Human Colon Carcinoma Cells.
AB  - BACKGROUND: Hypovitaminosis D is associated with an adverse prognosis in colon
      cancer patients, possibly due to the effects of the vitamin on the immune system.
      Antibody-dependent cell-mediated cytotoxicity (ADCC) significantly contributes to
      the anti-tumor effects of monoclonal antibodies, including cetuximab, an
      epidermal growth factor receptor (EGFR)-targeted monoclonal antibody that is
      frequently added to chemotherapy in the treatment of colon cancer. OBJECTIVE: The
      present study evaluates the association between vitamin D serum levels and the
      ability of ex vivo NK cells to support cetuximab-mediated ADCC in colon cancer
      cell lines. METHODS: Blood samples were obtained from 124 healthy volunteers and
      serum vitamin D was determined by RIA. NK cells were isolated from each sample
      and added to human colorectal carcinoma cells with or without cetuximab, and ADCC
      was assessed using a colorimetric lactate dehydrogenase assay. RESULTS:
      Correlation analysis indicates a significant, gender- and age-independent
      association between vitamin D levels and cetuximab-induced ADCC on HT29 cells,
      where NK cells from samples with vitamin D < 20 ng/mL are significantly less
      efficient in inducing ADCC. A confirmatory study on two additional colon cancer
      cell lines yielded similar results. CONCLUSIONS: These data suggest that vitamin
      D supplementation in vitamin-deficient/insufficient colorectal cancer patients
      could improve cetuximab-induced ADCC.

PMID- 30090972
TI  - Metabolic profile determination of 25N-NBOMe in human liver microsomes by liquid
      chromatography-quadrupole time-of-flight mass spectrometry.
AB  - 2-(2,5-Dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl)ethanamine (25N-NBOMe, 2C-N
      NBOMe, NBOMe-2C-N) is a novel synthetic psychoactive substance of the
      phenethylamine chemical class. A few metabolism studies have been conducted for
      25I-NBOMe, 25B-NBOMe, and 25C-NBOMe, and others, whereas 25N-NBOMe metabolism has
      not been researched. In this study, the in vitro metabolism of 25N-NBOMe was
      investigated with human liver microsomes, and the reaction mixture was analyzed
      using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q
      TOF/MS). Formation of 14 metabolites (M1-M14) was yielded with incubation of 25N
      NBOMe in human liver microsomes in the presence of NADPH. The metabolites were
      structurally characterized on the basis of accurate mass analysis and MS/MS
      fragmentation patterns. The biotransformations included hydroxylation, O
      demethylation, N-dealkylation, nitro reduction, dehydrogenation, carbonylation,
      and combinations thereof. Hydroxyl metabolite was the most abundant compound
      after the phase I process. These results provide helpful information establishing
      biomarkers in case of 25N-NBOMe ingestion.

PMID- 30090973
TI  - Concentration of Bioactive Compounds from Elderberry (Sambucus nigra L.) Juice by
      Nanofiltration Membranes.
AB  - For the first time the chemical profile, physico-chemical parameters, inhibition
      of carbohydrate hydrolysing enzymes associated with type 2 diabetes, and radical
      scavenging properties of Sambucus nigra L. (elderberry) juice treated by
      nanofiltration (NF) were investigated. Three commercial NF membranes with
      different molecular weight cut-off (MWCO) (400 and 1000 Da) and polymeric
      material (composite fluoro-polymer and polyethersulphone) were tested. According
      to HPLC analyses, most part of bioactive compounds were retained by the NF
      membranes producing a retentate fraction of interest for the production of
      functional foods. The NP030 membrane, a polyethersulphone membrane with a MWCO of
      400 Da, exhibited the highest rejection towards phenolic compounds when compared
      with the other selected membranes. Accordingly, the produced retentate fractions
      exhibited the highest radical scavenging activity.

PMID- 30090974
TI  - Population-Pharmacokinetic and Covariate Analysis of Lurbinectedin (PM01183), a
      New RNA Polymerase II Inhibitor, in Pooled Phase I/II Trials in Patients with
      Cancer.
AB  - BACKGROUND AND OBJECTIVES: Lurbinectedin is an inhibitor of RNA polymerase II
      currently under clinical development for intravenous administration as a single
      agent and in combination with other anti-tumor agents for the treatment of
      several tumor types. The objective of this work was to develop a population
      pharmacokinetic model in this patient setting and to elucidate the main
      predictors to guide the late stages of development. METHODS: Data from 443
      patients with solid and hematologic malignancies treated in six phase I and three
      phase II trials with lurbinectedin as a single agent or combined with other
      agents were included in the analysis. The potential influence of demographic, co
      treatment, and laboratory characteristics on lurbinectedin pharmacokinetics was
      evaluated. RESULTS: The final population-pharmacokinetic model was an open three
      compartment model with linear distribution and linear elimination from the
      central compartment. Population estimates for total plasma clearance, and
      apparent volume at steady state were 11.2 L/h and 438 L, respectively. Inter
      individual variability was moderate for all parameters, ranging from 20.9 to
      51.2%. High alpha-1-acid glycoprotein and C-reactive protein, and low albumin
      reduced clearance by 28, 20, and 20%, respectively. Co-administration of
      cytochrome P450 3A inhibitors reduced clearance by 30%. Combinations with other
      anti-tumor agents did not modify the pharmacokinetics of lurbinectedin
      significantly. CONCLUSION: The population-pharmacokinetic model indicated neither
      a dose nor time dependency, and no clinically meaningful pharmacokinetic
      differences were found when co-administered with other anticancer agents. A
      chronic inflammation pattern characterized by decreased albumin and increased C
      reactive protein and alpha-1-acid glycoprotein levels led to high lurbinectedin
      exposure. Co-administration of cytochrome P450 3A inhibitors increased
      lurbinectedin exposure.

PMID- 30090975
TI  - Acanthopanax senticosus Protects Structure and Function of Mesencephalic
      Mitochondria in A Mouse Model of Parkinson's Disease.
AB  - OBJECTIVE: To investigate the neuro-protective effects of Acanthopanax senticosus
      Harms (EAS) on mesencephalic mitochondria and the mechanism of action, using a
      mouse model of Parkinson's disease (PD). METHODS: The chemical fingerprint
      analysis of the extract of Acanthopanax senticosus Harms (EAS) was performed
      using the ultra performance liquid chromatograph and time of flight mass
      spectrometry. Thirty mice were randomly divided into the control group, the MPTP
      model group, and the EAS treated group with MPTP (MPTP+EAS group, 10 in each
      group). The MPTP model group and the MPTP+EAS group received MPTP-HCl (30 mg/kg
      i.p) once a day for 5 days. The control group received an equal volume of saline
      (20 mL/kg i.p) once a day for 5 days. Induced by 1-methyl-4-phenyl-1, 2, 3, 6
      tetrahydropyridine hydrochloride daily (MPTP-HCl, 30 mg/kg) for 5 days, the PD
      mice were treated with EAS at 45.5 mg/kg daily for 20 days. The behavioral
      testing of mice was carried out using the pole-climbing test. The integrity and
      functions of neurons were examined in mesencephalic mitochondria in a PD mouse
      model, including nicotinamide adenine dinucleotide dehydrogenase ubiquinone
      flavoprotein 2 (NDUFV2), mitochondrially encoded nicotinamide adenine
      dinucleotide dehydrogenase 1 (MT-ND1), succinate dehydrogenase complex subunit A
      (SDHA), and succinate dehydrogenase cytochrome b560 subunit (SDHC). RESULTS:
      After treatment with EAS, the behavioral changes induced by MPTP were attenuated
      significantly (P<0.05). EAS protected the mesencephalic mitochondria from
      swelling and attenuated the decreases in their membrane potential (both P<0.05),
      which was supported by an ultra-structural level analysis. The changes in
      reactive oxygen species (ROS), malonic dialdehyde (MDA), oxidative
      phosphorylation (OXPHOS) system 4 subunits levels and PD-related proteins
      expressions (parkin, Pink1, DJ-1, alpha-synuclein, and Lrrk2) reverted to near
      normal levels (all P<0.05), based on the results of immune-histological and
      Western blotting observations. CONCLUSIONS: The neuro-protective effects of EAS
      are linked to protecting mice against MPTP-induced mitochondrial dysfunction and
      structural damage. Therefore, EAS is a promising candidate for the prevention or
      treatment of mitochondrial neurodegenerative disorders, such as PD.

PMID- 30090976
TI  - Effects of Flower Buds Extract of Tussilago farfara on Focal Cerebral Ischemia in
      Rats and Inflammatory Response in BV2 Microglia.
AB  - OBJECTIVE: To investigate the effects of the flower buds extract of Tussilago
      farfara Linne (Farfarae Flos; FF) on focal cerebral ischemia through regulation
      of inflammatory responses in activated microglia. METHODS: Brain ischemia was
      induced in Sprague-Dawley rats by a transient middle cerebral artery occlusion
      (tMCAO) for 90 min and reperfusion for 24 h. Twenty rats were randomly divided
      into 4 groups (n=5 per group): normal, tMCAO-induced ischemic control, tMCAO plus
      FF extract 300 mg/kg-treated, and tMCAO plus MK-801 1 mg/kg-treated as reference
      drug. FF extract (300 mg/kg, p.o.) or MK-801 (1 mg/kg, i.p.) was administered
      after reperfusion. Brain infarction was measured by 2,3,5,-triphenyltetrazolium
      chloride staining. Neuronal damage was observed by haematoxylin eosin, Nissl
      staining and immunohistochemistry using anti-neuronal nuclei (NeuN), anti-glial
      fibrillary acidic protein (GFAP), and anti-CD11b/c (OX42) antibodies in ischemic
      brain. The expressions of inducible nitric oxide synthase (iNOS), tumor necrosis
      factor (TNF-alpha), and hypoxia-inducible factor-1a (HIF-1alpha) were determined
      by Western blot. BV2 microglial cells were treated with FF extract or its main
      bioactive compound, tussilagone with or without lipopolysaccharide (LPS). Nitric
      oxide (NO) production was measured in culture medium by Griess assay. The
      expressions of iNOS, COX-2 and pro-inflammatory cytokines mRNA were analyzed by
      reverse transcription-polymerase chain reaction. The expression of iNOS, and COX
      2 proteins, the phosphorylation of ERK1/2, JNK, and p38 MAPK and the nuclear
      expression of NF-kappaB p65 in BV2 cells were determined by Western blot.
      RESULTS: FF extract significantly decreased brain infarctions in ischemic rats
      (P<0.01). The neuronal death and the microglia/astrocytes activation in ischemic
      brains were inhibited by FF extract. FF extract also suppressed iNOS, TNF-alpha,
      and HIF-1alpha expression in ischemic brains. FF extract (0.2 and 0.5 mg/mL,
      P<0.01) and tussilagone 20 and 50 MUmol/L, P<0.01) significantly decreased LPS
      induced NO production in BV2 microglia through downregulation of iNOS mRNA and
      protein expression. FF extract and tussilagone significantly inhibited LPS
      induced expression of TNF-alpha, IL-1beta, and IL-6 mRNA, and also suppressed the
      phosphorylation of ERK1/2, JNK and p38 MAPK and the nuclear expression of NF
      kappaB in a dose-dependent manner. CONCLUSIONS: FF extract has a neuroprotective
      effect in ischemic stroke by the decrease of brain infarction, and the inhibition
      of neuronal death and microglial activation-mediated inflammatory responses.

PMID- 30090977
TI  - Correction to: Continuous flash suppression and monocular pattern masking impact
      subjective awareness similarly.
AB  - There is an error in Fig. 4, part A. In the "continuous flash suppression" box,
      the labels "non-dominant eye" and "dominant eye" need to be switched with each
      other. The corrected Fig. 4 appears below.

PMID- 30090978
TI  - Capacity limit of ensemble perception of multiple spatially intermixed sets.
AB  - The visual system is remarkably efficient at extracting summary statistics from
      the environment. Yet at any given time, the environment consists of many groups
      of objects distributed over space. Thus, the challenge for the visual system is
      to summarize over multiple groups. The current study investigates the capacity
      and computational efficiency of ensemble perception, in the context of perceiving
      mean sizes of multiple spatially intermixed groups of circles. In a series of
      experiments, participants viewed an array of one to eight sets of circles. Each
      set contained four circles in the same colors, but with different sizes.
      Participants estimated the mean size of a probed set. The set that would be
      probed was either known before onset of the array (pre-cue condition) or
      afterwards (post-cue condition). By comparing estimation error in the pre-cue and
      post-cue conditions, we found that participants could reliably estimate mean
      sizes for approximately two sets (Experiment 1). Importantly, this capacity was
      robust against attention bias toward individual objects in the sets (Experiment
      2). Varying the exposure time to stimulus arrays did not increase the capacity
      limit, suggesting that ensemble perception could be limited by an internal
      resource constraint, rather than the speed of information encoding (Experiment
      3). Moreover, we found that the visual system could not encode and hold more
      individual items than ensemble representations (Experiment 4). Taken together,
      these results suggest that ensemble perception provides an efficient way of
      information processing but with constraints.

PMID- 30090979
TI  - Diffusion parameters of the core of cingulum are associated with age-related
      ventricular enlargement: a diffusion tensor tractography study.
AB  - PURPOSE: To evaluate the influence of the size of lateral ventricles on diffusion
      parameters of the normal cingulate bundle. METHODS: Eighty normal subjects (17-55
      years) underwent MRI at 3 T including diffusion tensor imaging. Superior (SC) and
      inferior (IC) cingulum were analyzed separately. Mean diffusivity (MD0.30) and
      fractional anisotropy (FA0.30) were measured by tractography at FA threshold
      0.30; further diffusion parameters were analyzed by tractography-based core
      analysis in volumes of 3.0 cm3/1.5 cm3. The diffusion parameters were correlated
      with corresponding cross-sectional coronal areas of lateral ventricles. The
      analysis was performed also separately for young (17-34) and middle-aged (35-55)
      subjects. RESULTS: FA0.30 values did not correlate with ventricular size, but
      there was a weak negative correlation (r = - 0.225) between MD0.30 of SC and
      ventricular size. In all controls and in the older age group, ventricular size
      correlated positively with core FA of SC (r = 0.262/r = 0.391) and negatively
      with mean diffusivity (r = - 0.324/r = - 0.303) and radial diffusivity (lambda2:
      r = - 0.238/r = - 0.277; lambda3: r = - 0.353/r = - 0.424) of the core of SC. In
      the younger age group, only the mean diffusivity of SC correlated with
      ventricular size (r = - 0.273). Ventricular size was not associated with axial
      diffusivity. The core parameters of IC did not correlate with ventricular size.
      CONCLUSION: Radial diffusivity of the core of cingulum decreases in age-dependent
      ventricular enlargement, which can be related to tissue compaction with
      stretching of axons and diminution of extracellular spaces. The phenomenon, which
      is reverse to the assumed effect of age-related myelin loss, can influence on DTI
      parameters in middle-aged subjects.

PMID- 30090980
TI  - Spinal intradural extramedullary cavernous hemangioma.
AB  - Spinal intradural extramedullary cavernous hemangiomas are very rare. Mixed
      intensities on T1- andT2-weighted images due to repeated hemorrhages and poor to
      absent contrast-enhancement are the most common imaging features of the disease
      allowing accurate differentiation from the far more frequent meningiomas and
      schwannomas of similar location.

PMID- 30090981
TI  - Air bubble artifact reduction in post-mortem whole-brain MRI: the influence of
      receiver bandwidth.
AB  - Air bubble artifacts on SWI post-mortem MRI studies may interfere with the
      detection of cerebral microbleeds. We investigated whether the utilization of a
      higher receiver bandwidth of 500 Hz/pixel could reduce cortical air bubble
      artifacts without compromising the detection of cerebral microbleeds in high
      field MRI. All microbleeds remained clearly visible whereas a reduction of 17% of
      the long axis of the "halo" magnitude artifacts was achieved. On corresponding
      phase images, air bubble artifacts appeared identical.

PMID- 30090982
TI  - Environmental Toxicant Exposure and Hypertensive Disorders of Pregnancy: Recent
      Findings.
AB  - PURPOSE OF REVIEW: To assess the strength of evidence for associations between
      environmental toxicants and hypertensive disorders of pregnancy, suggest
      potential biological mechanisms based on animal and in vitro studies, and
      highlight avenues for future research. RECENT FINDINGS: Evidence is strongest for
      links between persistent chemicals, including lead, cadmium, organochlorine
      pesticides, and polycyclic biphenyls, and preeclampsia, although associations are
      sometimes not detectable at low-exposure levels. Results have been inconclusive
      for bisphenols, phthalates, and organophosphates. Biological pathways may include
      oxidative stress, epigenetic changes, endocrine disruption, and abnormal
      placental vascularization. Additional prospective epidemiologic studies beginning
      in the preconception period and extending postpartum are needed to assess the
      life course trajectory of environmental exposures and women's reproductive and
      cardiovascular health. Future studies should also consider interactions between
      chemicals and consider nonlinear associations. These results confirm
      recommendations by the International Federation of Gynecology and Obstetrics, the
      American Society for Reproductive Medicine, the American Academy of Pediatrics,
      and the Endocrine Society that providers counsel their pregnant patients to limit
      exposure to environmental toxicants.

PMID- 30090983
TI  - Multiple sclerosis incidence in Tuscany from administrative data.
AB  - BACKGROUND: Italy is a high-risk area for multiple sclerosis with 110,000
      prevalent cases estimated at January 2016 and 3400 annual incident cases. To
      study multiple sclerosis epidemiology, it is preferable to use population-based
      studies, e.g., with a registry. A valid alternative to obtain data on entire
      population is from administrative sources. OBJECTIVE: To estimate the incidence
      of multiple sclerosis in Tuscany using a case-finding algorithm based on
      administrative data. METHODS: In a previous study, we calculated the prevalence
      in Tuscany using a validated case-finding algorithm based on administrative data.
      Incident cases were identified as a subset of prevalent cases among those
      patients not traced in the years before the analysis period, and the date of the
      first multiple sclerosis-related claim was considered the incidence date of
      multiple sclerosis diagnosis. We examined the period 2011-2015. RESULTS: We
      identified 1147 incident cases with annual rates ranged from 5.60 per 100,000 in
      2011 to 6.58 in 2015. CONCLUSIONS: We found a high incidence rate, similarly to
      other Italian areas, especially in women, that may explain the increasing
      prevalence in Tuscany. To confirm this data and to calculate the possible bias
      caused by our inclusion method, we will validate our algorithm for incident
      cases.

PMID- 30090984
TI  - Profiling of microRNAs modulating cytomegalovirus infection in astrocytoma
      patients.
AB  - Astrocytoma is recognized as the most common neoplasm of the brain with
      aggressive progression. The therapeutic regime for glioblastoma, the most
      aggressive astrocytoma, often consists of aggressive chemo and radiotherapy. The
      present holistic approaches, however, have failed to influence the quality life
      of patients. Therefore, it is necessary to understand the underlying mechanisms
      of its progression for updated therapeutic evaluation. Human cytomegalovirus
      (HCMV) is reported to be associated with glioblastoma progression. The hypothesis
      still remains controversial due to the lack of concrete evidences. Here, we
      report the profile of miRNAs encoded by human host and the cytomegalovirus (CMV)
      involved in modulation of CMV infection in surgically resected human astrocytoma
      tissue samples of various malignancy grades (n = 24). Total RNA from the control
      brain and tumor tissues was extracted by TriZol reagent. The expression levels of
      the mature form of miRNA were detected by real-time PCR. Primarily, we found the
      upregulation of miR-210-3p, miR-155-5p, miR-UL-112-3p, miR-183-5p, and miR-223-5p
      in high-grade astrocytic tumors as compared with low-grade tumor tissues. miR-214
      3p is significantly expressed in control brain tissues and its expression
      decreased with astrocytoma grade progression. This miRNA was reported to be
      associated with antiviral proprieties. Among CMV-encoded miRNA, miR-UL-112-3p was
      significantly upregulated in glioblastoma tissue samples and may be involved in
      providing immune escape to the virus as well as involved in modulating the immune
      microenvironment of glioblastoma. Taken together, we conclude the possible
      involvement of miRNAs in modulating the CMV dependent astrocytoma progression.

PMID- 30090985
TI  - Morvan's syndrome-is a pathogen behind the curtain?
AB  - Morvan's syndrome is a rare syndrome of likely autoimmune etiology characterized
      by peripheral nerve hyperexcitability, dysautonomia, insomnia, and fluctuating
      delirium with prominent hallucinations. Since its first mention in 1890, less
      than 100 cases have been described in literature. The largest existing review
      includes details of 29 cases. This case series describes 4 cases (M = 4) of
      Morvan's syndrome which presented between May and November 2017 to a single
      tertiary care referral teaching hospital in north India. All the four patients
      manifested behavioral abnormalities, sleep disturbances, hallucinations,
      autonomic dysfunction, and clinical signs of peripheral nerve hyperexcitability,
      mostly as myokymia. Two of the patients had Anti-CASPR2 (contactin-associated
      protein 2) antibodies. Three of them had electromyography features of peripheral
      nerve hyperexcitability and only one had elevated cerebrospinal fluid protein
      level. We hypothesize that Morvan's syndrome and other less characterized
      autoimmune encephalitis/peripheral nervous system syndromes may have infectious
      triggers. A possible viral trigger may result in generation of autoantibodies
      which result in the typical manifestations. We base these hypotheses on the
      finding of four cases of an orphan disease within a short period of time in a
      limited geographical distribution.

PMID- 30090987
TI  - ?

PMID- 30090986
TI  - [Thoracic trauma : Current aspects on interdisciplinary management of thoracic
      wall and organ injuries].

PMID- 30090988
TI  - Enhanced Production of Phenolic Compounds in Compact Callus Aggregate Suspension
      Cultures of Rhodiola imbricata Edgew.
AB  - Rhodiola imbricata is a rare medicinal plant of the trans-Himalayan region of
      Ladakh. It is used for the treatment of numerous health ailments. Compact callus
      aggregate (CCA) suspension cultures of Rhodiola imbricata were established to
      counter extinction threats and for production of therapeutically valuable
      phenolic compounds to meet their increasing industrial demands. The present study
      also investigated the effect of jasmonic acid (JA) on production of phenolic
      compounds and bioactivities in CCA suspension cultures. CCA suspension cultures
      established in an optimized Murashige and Skoog medium supplemented with 30 g/l
      sucrose, 3 mg/l NAA, and 3 mg/l BAP showed maximum biomass accumulation (8.43 g/l
      DW) and highest salidroside production (3.37 mg/g DW). Upon 100 MUM JA treatment,
      salidroside production (5.25 mg/g DW), total phenolic content (14.69 mg CHA/g
      DW), total flavonoid content (4.95 mg RE/g DW), and ascorbic acid content (17.93
      mg/g DW) were significantly increased in cultures. In addition, DPPH-scavenging
      activity (56.32%) and total antioxidant capacity (60.45 mg QE/g DW) were
      significantly enhanced upon JA treatment, and this was positively correlated with
      increased accumulation of phenolic compounds. JA-elicited cultures exhibited
      highest antimicrobial activity against Escherichia coli. This is the first report
      describing the enhanced production of phenolic compounds and bioactivities from
      JA-elicited CCA suspension cultures of Rhodiola imbricata.

PMID- 30090990
TI  - Lipid Screening, Action, and Follow-up in Children and Adolescents.
AB  - PURPOSE OF REVIEW: To create awareness for the devastating influence of high
      cholesterol in familial hypercholesterolaemia (FH) on vessel walls. Persons with
      high LDL-C and a known mutation associated with FH have a 22-fold increase in CVD
      compared with those with a normal LDL-C and no genetic mutation. If the awareness
      of the need to diagnose and treat this genetic disorder at an early stage
      increases, great atherosclerotic impact later in life could be avoided. Every
      minute a child with heterozygous FH is born somewhere in the world and every day
      a child with homozygous FH is born. RECENT FINDINGS: Recent findings include
      effective therapy on statins from the age of 6 years, with already normalization
      of the intima-media thickness within 2 years. Newer types of drugs, with the same
      safety profile and perhaps even more effective, will become available in
      childhood in the near future. Open for discussion will be whom to treat and with
      what type of treatment. Next generation sequencing will perhaps easily select
      those in need of treatment and those at risk of adverse effects. At the end of
      this review, statements and recommendations for children and adolescents with
      heterozygous FH are listed.

PMID- 30090991
TI  - A single-arm, retrospective analysis of the incidence of febrile neutropenia
      using same-day versus next-day pegfilgrastim in patients with gastrointestinal
      cancers treated with FOLFOX or FOLFIRI.
AB  - BACKGROUND: Practice patterns of same-day versus next-day pegfilgrastim vary in
      numerous practice settings across the country. Current utilization with same-day
      pegfilgrastim reduced overall visits and reduced treatment time for chemotherapy
      administration. OBJECTIVE: To assess the efficacy and safety of same-day versus
      next-day pegfilgrastim in patients with colorectal cancer. METHODS: Patient data
      was extracted through electronic health records (EHR) search of ICD-9 codes that
      matched patients with CRC and treated with FOLFOX or FOLFIRI from November 2013
      to January 2016. The incidence rates of primary and secondary endpoints were
      estimated for patients who received either FOLFOX or FOLFIRI and same-day
      pegfilgrastim with 2-sided 95% confidence intervals. Fisher's exact test for 2 *
      2 contingency tables was used to compare the incidence of primary and secondary
      endpoints between the two study groups performed at the alpha = 0.05 significance
      level. A study by Hecht et al. served as a historical control for next-day
      pegfilgrastim. RESULTS: A total of 109 out of an initial 330 patients with
      appropriate ICD-9 criteria were eligible for study inclusion. The primary
      endpoint of incidence of FN recorded over 4 chemotherapy cycles with either
      FOLFOX6 or FOLFIRI occurred in 3.7% of patients (95% CI, 1.1-9.4%). Secondary
      endpoints also occurred with a relatively low incidence: 13 patients developed
      grades 3/4 neutropenia (11.9%; 95% CI, 7.0-19.5%); 11 patients required dose
      reductions because of neutropenia or FN (10.1%; 95% CI, 5.6-17.3%); and 5
      patients were hospitalized due to neutropenia or FN (4.6%; 1.7-10.6%). There were
      4 reported events of FN (3.2%; 95% CI, 1.0-8.3%) for those who received next-day
      pegfilgrastim compared to 11 events in the placebo group (9.4%; 95% CI, 5.1
      16.4%). The incidence of dose delays or dose reductions due to neutropenia or FN
      were 5 (4.1%, 95% CI, 1.5-9.4%) in the next-day pegfilgrastim group versus 26
      (22.1%, 95% CI, 15.5-30.4%) in the placebo group. LIMITATIONS: The study was
      retrospective in design and utilized a historical control for the comparator.
      CONCLUSIONS: Our study results suggest that same-day pegfilgrastim administration
      may be a safe and effective alternative to 24-h post-chemotherapy administration
      in patients with esophageal, gastric, appendiceal, or colorectal cancer
      undergoing treatment with FOLFOX or FOLFIRI.

PMID- 30090989
TI  - Liquid chromatographic nanofractionation with parallel mass spectrometric
      detection for the screening of plasmin inhibitors and (metallo)proteinases in
      snake venoms.
AB  - To better understand envenoming and to facilitate the development of new
      therapies for snakebite victims, rapid, sensitive, and robust methods for
      assessing the toxicity of individual venom proteins are required.
      Metalloproteinases comprise a major protein family responsible for many aspects
      of venom-induced haemotoxicity including coagulopathy, one of the most
      devastating effects of snake envenomation, and is characterized by fibrinogen
      depletion. Snake venoms are also known to contain anti-fibrinolytic agents with
      therapeutic potential, which makes them a good source of new plasmin inhibitors.
      The protease plasmin degrades fibrin clots, and changes in its activity can lead
      to life-threatening levels of fibrinolysis. Here, we present a methodology for
      the screening of plasmin inhibitors in snake venoms and the simultaneous
      assessment of general venom protease activity. Venom is first chromatographically
      separated followed by column effluent collection onto a 384-well plate using
      nanofractionation. Via a post-column split, mass spectrometry (MS) analysis of
      the effluent is performed in parallel. The nanofractionated venoms are exposed to
      a plasmin bioassay, and the resulting bioassay activity chromatograms are
      correlated to the MS data. To study observed proteolytic activity of venoms in
      more detail, venom fractions were exposed to variants of the plasmin bioassay in
      which the assay mixture was enriched with zinc or calcium ions, or the chelating
      agents EDTA or 1,10-phenanthroline were added. The plasmin activity screening
      system was applied to snake venoms and successfully detected compounds exhibiting
      antiplasmin (anti-fibrinolytic) activities in the venom of Daboia russelii, and
      metal-dependent proteases in the venom of Crotalus basiliscus. Graphical abstract
      ?.

PMID- 30090992
TI  - External validation of three risk stratification rules in patients presenting
      with pulmonary embolism and cancer.
AB  - Numerous risk stratification rules exist to predict post-pulmonary embolism (PE)
      mortality; however, few were designed for use in cancer patients. In the EPIPHANY
      registry, adapted versions of common rules (the Hestia criteria, Pulmonary
      Embolism Severity Index [PESI], and simplified PESI [sPESI]) displayed high
      sensitivity for prognosticating mortality in PE patients with cancer. These
      adapted rules have yet to be externally validated. Therefore, we sought to
      evaluate the performance of an adapted Hestia criteria, PESI, and sPESI for
      predicting 30-day post-PE mortality in patients with cancer. We identified
      consecutive, adults presenting with objectively confirmed PE and cancer to our
      institution (November 2010 to January 2014). The proportion of patients
      categorized as low or high risk by these three risk stratification rules was
      calculated, and each rule's accuracy for predicting 30-day all-cause mortality
      was determined. Of the 124 patients with PE and active cancer identified, 25
      (20%) experienced mortality at 30 days. The adapted Hestia criteria categorized
      23 (19%) patients as low risk, while exhibiting a sensitivity of 88% (95%
      confidence interval [CI] = 68-97%), a negative predictive value NPV of 87% (95%
      CI = 65-97%), and a specificity of 20% (95% CI = 13-30%). A total of 38 (31%) and
      30 (24%) patients were low risk by the adapted PESI and sPESI, with both
      displaying sensitivities of 92% and NPVs > 93%. Specificities were 36% (95% CI =
      27-47%) and 28% (95% CI = 20-38%) for PESI and sPESI. In our external validation,
      the adapted Hestia, PESI, and sPESI demonstrated high sensitivity but low
      specificity for 30-day PE mortality in patients with cancer. Larger, prospective
      trials are needed to optimize strategies for risk stratification in this
      population.

PMID- 30090993
TI  - Mapping the Psychotic Mind: a Review on the Subjective Structure of Thought
      Insertion.
AB  - Delusions of thought insertion involve subjects claiming that external agents of
      different nature had placed thoughts into their minds/heads. However, despite
      being regarded as one of the most severe and complex symptoms of psychotic
      disorders, a number of disagreements surround the description of its most
      fundamental phenomenology. This work has reviewed classic and current research on
      thought insertion in order to examine and clarify its main experiential features
      as reported by patients from a first-person perspective. The review shows that
      such features can be grouped into two categories: (i) experiential changes
      characterizing the period preceding the adoption of the delusion and, (ii)
      subjective features of full-blown delusional cases. While the discussion of the
      latter set of experiential features has received some attention within
      literature, the examination of the former set has been largely neglected. After
      this, the review offers a discussion of the most important conceptual
      disagreements surrounding the phenomenological descriptions of the symptom.
      Overcoming disagreements regarding the experiential structure of thought
      insertion is fundamental to elaborate phenomenologically and empirically coherent
      explanatory theories of the symptom and advance its clinical treatment.

PMID- 30090994
TI  - Community Mental Health Center Integrated Care Outcomes.
AB  - Despite the compelling logic for integrating care for people with serious mental
      illness, there is also need for quantitative evidence of results. This
      retrospective analysis used 2013-2015 data from seven community mental health
      centers to measure clinical processes and health outcomes for patients receiving
      integrated primary care (n = 18,505), as well as hospital use for the 3943
      patients with hospitalizations during the study period. Bivariate and regression
      analyses tested associations between integrated care and preventive screening
      rates, hemoglobin A1c levels, and hospital use. Screening rates for body-mass
      index, blood pressure, smoking, and hemoglobin A1c all increased very
      substantially during integrated care. More than half of patients with baseline
      hypertension had this controlled within 90 days of beginning integrated care.
      Among patients hospitalized at any point during the study period, the probability
      of hospitalization in the first year of integrated care decreased by 18
      percentage points, after controlling for other factors such as patient severity,
      insurance status, and demographics (p < .001). The average length of stay was
      also 32% shorter compared to the year prior to integrated care (p < .001).
      Savings due to reduced hospitalization frequency alone exceeded $1000 per
      patient. Data limitations restricted this study to a pre-/post-study design.
      However, the magnitude and consistency of findings across different outcomes
      suggest that for people with serious mental illness, integrated care can make a
      significant difference in rates of preventive care, health, and cost-related
      outcomes.

PMID- 30090995
TI  - Agustin ("Tino") Castellanos Jr. (1927-2017): The Journal Editors honor the grand
      legacy of a gentleman and a scholar.

PMID- 30090996
TI  - Second-generation cryoballoon ablation for recurrent atrial fibrillation after an
      index cryoballoon procedure: a staged strategy with variable balloon size.
AB  - PURPOSE: Currently, information on the optimal approach of redo procedures for
      paroxysmal atrial fibrillation (PAF) is limited. Radiofrequency ablation is the
      preferred technique, with reported success rates of 50-70% at 1-2 years, whereas
      only few reports exist on redo cryoballoon (CB) ablations. We describe outcomes
      on a systematic approach of repeat procedures with a second-generation
      cryoballoon (CB-2) after a successful index CB ablation. METHODS: Cohort study of
      40 consecutive patients with recurrent PAF (55% male), median CHA2DS2-VASc score
      1 (IQR 0-3). Per protocol, a staged variable balloon size strategy was followed
      with a different balloon size during the redo as compared to the index procedure.
      Minimal follow-up was 12 months (median 17 months [IQR 14-39]). RESULTS: Overall,
      120 pulmonary veins (PVs) (75%) showed chronic isolation: 64% (41/64) for first
      generation cryoballoon (CB-1) and 82% (79/96) for CB-2 index procedures,
      respectively (p = 0.01). The overall mean number of reconnected PVs per patient
      was 1.0 (40/40): 1.4 for CB-1 and 0.7 for CB-2 index procedures (p = 0.008).
      Phrenic nerve palsies (n = 7) resolved before the end of the procedure. At 1
      year, 70% of patients were free of recurrent AF. In multivariate analysis, the
      only independent predictor of recurrence was the number of prior cardioversions.
      CONCLUSIONS: A systematic approach of repeat procedures with a CB-2 using a
      different balloon size than during the index CB ablation is safe, with acceptable
      1-year outcomes. Future comparative studies on the optimal redo technique and
      approach are warranted to further improve rhythm control in AF.

PMID- 30090997
TI  - Detection of Atrial Fibrillation in Cryptogenic Stroke.
AB  - PURPOSE OF REVIEW: To summarize the literature on the detection of atrial
      fibrillation (AF) in patients with "cryptogenic" stroke, a cohort including about
      25% of all ischemic stroke patients and patients with embolic stroke of
      undetermined source (ESUS). RECENT FINDINGS: A first episode of AF is detected in
      up to one third of cryptogenic stroke and in up to one fourth of ESUS patients
      during long-term monitoring. AF prevalence correlates to patient selection,
      duration, and quality of ECG monitoring. Higher rates of AF were reported in
      stroke patients with left atrial pathology, specific ECG alterations, or
      increased natriuretic peptides. While AF detection impacts on medical stroke
      prevention in the vast majority of patients, patient selection for prolonged
      monitoring is largely left at the physician's discretion. AF detection after
      cryptogenic stroke or ESUS is a frequent, potentially causal condition. Whether
      subsequent oral anticoagulation may improve outcome remains open.

PMID- 30090998
TI  - Facet joint syndrome: from diagnosis to interventional management.
AB  - Low back pain (LBP) is the most common pain syndrome, and is an enormous burden
      and cost generator for society. Lumbar facet joints (FJ) constitute a common
      source of pain, accounting for 15-45% of LBP. Facet joint degenerative
      osteoarthritis is the most frequent form of facet joint pain. History and
      physical examination may suggest but not confirm facet joint syndrome. Although
      imaging (radiographs, MRI, CT, SPECT) for back pain syndrome is very commonly
      performed, there are no effective correlations between clinical symptoms and
      degenerative spinal changes. Diagnostic positive facet joint block can indicate
      facet joints as the source of chronic spinal pain. These patients may benefit
      from specific interventions to eliminate facet joint pain such as neurolysis, by
      radiofrequency or cryoablation. The purpose of this review is to describe the
      anatomy, epidemiology, clinical presentation, and radiologic findings of facet
      joint syndrome. Specific interventional facet joint management will also be
      described in detail. TEACHING POINTS: * Lumbar facet joints constitute a common
      source of pain accounting of 15-45%. * Facet arthrosis is the most frequent form
      of facet pathology. * There are no effective correlations between clinical
      symptoms, physical examination and degenerative spinal changes. * Diagnostic
      positive facet joint block can indicate facet joints as the source of pain. *
      After selection processing, patients may benefit from facet joint neurolysis,
      notably by radiofrequency or cryoablation.

PMID- 30090999
TI  - Tandem Androgenic and Psychological Shifts in Male Reproductive Effort Following
      a Manipulated "Win" or "Loss" in a Sporting Competition.
AB  - Male-male competition is involved in inter- and intrasexual selection, with both
      endocrine and psychological factors presumably contributing to reproductive
      success in human males. We examined relationships among men's naturally occurring
      testosterone, their self-perceived mate value (SPMV), self-esteem,
      sociosexuality, and expected likelihood of approaching attractive women versus
      situations leading to child involvement. We then monitored changes in these
      measures in male rowers (N = 38) from Cambridge, UK, following a manipulated
      "win" or "loss" as a result of an indoor rowing contest. Baseline results
      revealed that men with heightened testosterone and SPMV values typically had
      greater inclinations toward engaging in casual sexual relationships and a higher
      likelihood of approaching attractive women in a hypothetical social situation. As
      anticipated, both testosterone and SPMV increased following a manipulated
      "victory" and were associated with heightened sociosexuality, and increased
      expectations toward approaching attractive women versus individuals who would
      involve them in interacting with children after the race. SPMV and self-esteem
      appeared to mediate some of the effects of testosterone on post-race values.
      These findings are considered in the broader context of individual trade-offs
      between mating and parental effort and a model of the concurrent and dynamic
      androgenic and psychological influences contributing to male reproductive effort
      and success.

PMID- 30091000
TI  - Administration of an antagonist of P2X7 receptor to EAE rats prevents a decrease
      of expression of claudin-5 in cerebral capillaries.
AB  - Purinergic P2X receptors, when activated under pathological conditions,
      participate in induction of the inflammatory response and/or cell death. Both
      neuroinflammation and neurodegeneration represent hallmarks of multiple sclerosis
      (MS), an autoimmune disease of the central nervous system. In the current study,
      we examined whether P2X7R is expressed in brain microvasculature of rats
      subjected to experimental autoimmune encephalomyelitis (EAE) and explore possible
      relationships with blood-brain barrier (BBB) protein-claudin-5 after
      administration of P2X7R antagonist-Brilliant Blue G (BBG). Capillary fraction
      isolated from control and EAE rat brains was subjected to immunohistochemical and
      Western blot analyses. We document the presence of P2X7R in brain capillaries
      isolated from brain tissue of EAE rats. P2X7R is found to be localized on the
      abluminal surface of the microvessels and is co-expressed with PDGFbetaR, a
      marker of pericytes. We also show over-expression of this receptor in isolated
      capillaries during the course of EAE, which is temporally correlated with a lower
      protein level of PDGFbetaR, as well as claudin-5, a tight junction-building
      protein. Administration of a P2X7R antagonist to the immunized rats significantly
      reduced clinical signs of EAE and enhances protein expression of both claudin-5
      and PDGFbetaR. These results indicate that P2X7 receptor located on pericytes may
      contribute to pathological mechanisms operated during EAE in cerebral
      microvessels influencing the BBB integrity.

PMID- 30091001
TI  - Merely presenting one's own name along with target items is insufficient to
      produce a memory advantage for the items: A critical role of relational
      processing.
AB  - Using the self as a reference point at encoding produces a memory advantage over
      other types of encoding activities. Even simply co-presenting a target item with
      self-relevant versus other-relevant information can produce an "incidental" self
      memory advantage in the absence of any explicit task demand to evaluate the
      item's self-relevancy. In the present study, we asked whether an incidental self
      memory advantage results from (a) the mere co-presentation of a target item with
      self-relevant information at encoding or (b) relational processing between a
      target item and self-relevant information at encoding. During incidental
      encoding, words were presented in two different colors either above or below a
      name (the participant's own or another person's). Participants judged either the
      location of each word in relation to the name ("Is the word above or below the
      name?") or the color of each word to which the name had no relevance ("Is the
      word in red or green?"). In a subsequent memory test, we found a self-memory
      advantage for both items and their associated source features in the location
      judgment task but not in the color judgment task. Our findings show that a memory
      advantage for a target item presented with self-relevant versus other-relevant
      information is more likely when a task agenda places, via relational processing
      demands, the self-relevant/other-relevant information in the focus of attention
      along with the target item. Potential processes that mediate this attention
      dependent effect are discussed.

PMID- 30091002
TI  - TMS over the superior temporal sulcus affects expressivity evaluation of
      portraits.
AB  - When viewing a portrait, we are often captured by its expressivity, even if the
      emotion depicted is not immediately identifiable. If the neural mechanisms
      underlying emotion processing of real faces have been largely clarified, we still
      know little about the neural basis of evaluation of (emotional) expressivity in
      portraits. In this study, we aimed at assessing-by means of transcranial magnetic
      stimulation (TMS)-whether the right superior temporal sulcus (STS) and the right
      somatosensory cortex (SC), that are important in discriminating facial emotion
      expressions, are also causally involved in the evaluation of expressivity of
      portraits. We found that interfering via TMS with activity in (the face region
      of) right STS significantly reduced the extent to which portraits (but not other
      paintings depicting human figures with faces only in the background) were
      perceived as expressive, without, though, affecting their liking. In turn,
      interfering with activity of the right SC had no impact on evaluating either
      expressivity or liking of either paintings' category. Our findings suggest that
      evaluation of emotional cues in artworks recruit (at least partially) the same
      neural mechanisms involved in processing genuine biological others. Moreover,
      they shed light on the neural basis of liking decisions in art by art-naive
      people, supporting the view that aesthetic appreciation relies on a multitude of
      factors beyond emotional evaluation.

PMID- 30091004
TI  - Vagus nerve stimulation as a tool for enhancing extinction in exposure-based
      therapies.
AB  - RATIONALE: Emotionally traumatic experiences can lead to maladaptive memories
      that are enduring and intrusive. The goal of exposure-based therapies is to
      extinguish conditioned fears through repeated, unreinforced exposures to
      reminders of traumatic events. The extinction of conditioned fear depends upon
      the consolidation of new memories made during exposure to reminders. An
      impairment in extinction recall, observed in certain patient populations, can
      interfere with progress in exposure-based therapies, and the drive to avoid
      thoughts and reminders of the trauma can undermine compliance and increase
      dropout rate. Effective adjuncts to exposure-based therapies should improve the
      consolidation and maintenance of the extinction memory or improve the
      tolerability of the therapy. Under stressful conditions, the vagus nerve responds
      to elevations in epinephrine and signals the brain to facilitate the storage of
      new memories while, as part of the parasympathetic nervous system, it slows the
      sympathetic response. OBJECTIVE: Here, we review studies relevant to fear
      extinction, describing the anatomical and functional characteristics of the vagus
      nerve and mechanisms of vagus nerve stimulation (VNS)-induced memory enhancement
      and plasticity. RESULTS: We propose that stimulation of the left cervical vagus
      nerve during exposure to conditioned cues signals the brain to store new memories
      just as epinephrine or emotional arousal would do, but bypasses the peripheral
      sympathetic "fight-or-flight" response. CONCLUSIONS: In support of this
      hypothesis, we have found that VNS accelerates extinction and prevents
      reinstatement of conditioned fear in rats. Finally, we propose future studies
      targeting the optimization of stimulation parameters and the search for
      biomarkers of VNS effectiveness that may improve exposure therapy outcomes.

PMID- 30091003
TI  - Modulation of naturalistic maladaptive memories using behavioural and
      pharmacological reconsolidation-interfering strategies: a systematic review and
      meta-analysis of clinical and 'sub-clinical' studies.
AB  - BACKGROUND: Consolidated memories can undergo enduring modification through
      retrieval-dependent treatments that modulate reconsolidation. This represents a
      potentially transformative strategy for weakening or overwriting the maladaptive
      memories that underlie substance use and anxiety/trauma-related disorders.
      However, modulation of naturalistic maladaptive memories may be limited by
      'boundary conditions' imposed on the reconsolidation process by the nature of
      these memories. METHODS: We conducted a systematic review and meta-analyses of
      behavioural and pharmacological studies examining retrieval-dependent modulation
      of reward- and threat-related memories in (sub) clinical substance use and
      anxiety/trauma, respectively. RESULTS: Of 4938 publications assessed for
      eligibility, 8 studies of substance use and 10 of anxiety (phobia)- and trauma
      related symptoms were included in the meta-analyses. Overall, the findings were
      in the predicted direction, with most studies favouring the 'retrieval +
      treatment' condition. However, the magnitude of effects was dependent upon the
      nature of treatment, with pharmacological interventions showing a medium-sized
      effect (g = 0.59, p = 0.03) and behavioural treatments, a relatively small effect
      (g = 0.32, p = 0.10) in studies of phobia/trauma. Among studies of substance use,
      post-retrieval behavioural interventions yielded a larger effect (g = 0.60, p <
      0.001) relative to pharmacological treatments (g = - 0.03, p = 0.91), with
      treatment type being a statistically significant moderator (chi2(1) = 4.20, p =
      0.04). CONCLUSION: Modification of naturalistic maladaptive memories during
      reconsolidation appears to be a viable treatment strategy for substance use and
      phobias/trauma disorders. However, high levels of heterogeneity and
      methodological variation limit the strength of conclusions that can be drawn from
      the reviewed studies at this stage.

PMID- 30091006
TI  - Letter to the Editor Regarding the Article "Long Non-Coding RNA SPRY4-IT1 Can
      Predict Poor Prognosis in Digestive System Malignancies: a Meta-Analysis".

PMID- 30091005
TI  - Nucleocytoplasmic export of HDAC5 and SIRT2 downregulation: two epigenetic
      mechanisms by which antidepressants enhance synaptic plasticity markers.
AB  - RATIONALE: Antidepressant action has been linked to increased synaptic plasticity
      in which epigenetic mechanisms such as histone posttranslational acetylation
      could be involved. Interestingly, the histone deacetylases HDAC5 and SIRT2 are
      oppositely regulated by stress and antidepressants in mice prefrontal cortex
      (PFC). Besides, the neuroblastoma SH-SY5Y line is an in vitro neuronal model
      reliable to study drug effects with clear advantages over animals. OBJECTIVES: We
      aimed to characterize in vitro the role of HDAC5 and SIRT2 in antidepressant
      regulation of neuroplasticity. METHODS: SH-SY5Y cultures were incubated with
      imipramine, fluoxetine, and reboxetine (10 MUM, 2 and 24 h) as well as the
      selective HDAC5 (MC3822, 5 MUM, 24 h) or SIRT2 (33i, 5 MUM, 24 h) inhibitors. The
      regulation of the brain-derived neurotrophic factor (BDNF), the vesicular
      glutamate transporter 1 (VGLUT1), the acetylated histones 3 (AcH3) and 4 (AcH4),
      HDAC5, and SIRT2 was studied. Comparatively, the long-term effects of these
      antidepressants (21 days, i.p.) in the mice (C57BL6, 8 weeks) PFC were studied.
      RESULTS: Antidepressants increased both in vitro and in vivo expression of BDNF,
      VGLUT1, AcH3, and AcH4. Moreover, imipramine and reboxetine increased the
      phosphorylated form of HDAC5 (P-HDAC5), mediating its cytoplasmic export.
      Further, SIRT2 was downregulated by all antidepressants. Finally, specific
      inhibition of HDAC5 and SIRT2 increased neuroplasticity markers. CONCLUSIONS:
      This study supports the validity of the SH-SY5Y model for studying epigenetic
      changes linked to synaptic plasticity induced by antidepressants as well as the
      effect of selective HDAC inhibitors. Particularly, nucleocytoplasmic export of
      HDAC5 and SIRT2 downregulation mediated by antidepressants could enhance synaptic
      plasticity markers leading to antidepressant action.

PMID- 30091007
TI  - High Expression of PhospholipaseD2 Induced by Hypoxia Promotes Proliferation of
      Colon Cancer Cells through Activating NF- kappa Bp65 Signaling Pathway.
AB  - Hypoxia is a typical feature of colon cancer occurrence and progression. We have
      reported that high expression and activity of PhospholipaseD2 (PLD2) induced by
      hypoxia in colon cancer cells. In order to further investigate the role of PLD2
      in colon cancer under hypoxic conditions. MTT assay was used to detect the
      proliferation of human colon cancer cells (SW480 and SW620) under hypoxic
      conditions by decrease the PLD2 gene expression or inhibit the activity of PLD2.
      Expression level of p-P65/T-P65 and Cyclin D1 were detected in those cells
      treated as above through using western blot and RT-PCR analysis. Effect of NF
      Bp65 inhibitor (BAY-117082) on the proliferation and expression level of Cyclin
      D1 and PLD2 of colon cancer cells under hypoxic conditions were further
      analysised. As a result, decreased the expression of PLD2 or inhibited the
      activity of PLD2 leaded to the proliferation of hypoxia colon cancer cells
      reduced, and along with the expression level of p-P65/T-P65 and Cyclin D1
      reduced. However, inhibition the expression level of p-P65/T-P65 lead to the
      proliferation and expression of Cyclin D1 in those hypoxia colon cancer cells
      also reduced. In vivo growth decreased in response to PLD2 and NF-Bp65
      inhibition. Our study indicates that high expression of PLD2 induced by hypoxia
      promotes the proliferation of colon cancer cells, and it may elevate the
      expression level of Cyclin D1 through activating NF-Bp65 signaling pathway.
      Inhibition of the PLD2 expression may provide a new clue for treatment for colon
      cancer.

PMID- 30091008
TI  - The effects of granulocyte colony-stimulating factor on MR images of bone marrow.
AB  - Granulocyte colony-stimulating factor (G-CSF) analogs such as
      filgrastim/pegfilgrastim are increasingly used to enhance neutrophilic recovery
      after chemotherapy. It is widely known that, physiologically, pegfilgrastim
      stimulates marrow mitotic activity and induces marrow reconversion from fatty to
      cellular. However, there is limited literature discussing the effects of
      pegfilgrastim on musculoskeletal magnetic resonance imaging, with the consensus
      that marrow reconversion secondary to pegfilgrastim therapy is easily confounded
      with a malignant process, especially in patients with a history of cancer. We
      attempt to discuss the expected changes and MRI findings after pegfilgrastim
      therapy through a summary of current literature. Additionally, we provide images
      from our own practice to support the previously established findings. G-CSF
      stimulated reconversion can appear as patchy expansions of baseline hematopoietic
      marrow, but can also appear to be diffusely homogeneous, adding to its ambiguity.
      We conclude that using a baseline MRI, clinical information, and assessing
      sequential MRI changes in conjunction with pegfilgrastim therapy may aid the
      differentiation between benign and pathological change. We expand our discussion
      to include the effects of novel technologies, such as whole-body MRI, chemical
      shift imaging, and contrast agents in helping the distinction.

PMID- 30091009
TI  - The pattern of idiopathic isolated teres minor atrophy with regard to its two
      bundle anatomy.
AB  - OBJECTIVE: We aimed to analyze the pattern of teres minor atrophy with regard to
      its two-bundle anatomy and to assess its association with clinical factors.
      MATERIALS AND METHODS: Shoulder MRIs performed between January and December 2016
      were retrospectively reviewed. Images were evaluated for the presence and pattern
      of isolated teres minor atrophy. Isolated teres minor atrophy was categorized
      into complete or partial pattern, and partial pattern was further classified
      according to the portion of the muscle that was predominantly affected. The
      medical records were reviewed to identify clinical factors associated with teres
      minor atrophy. RESULTS: Seventy-eight shoulders out of 1,264 (6.2%) showed
      isolated teres minor atrophy; complete pattern in 41.0%, and partial pattern in
      59.0%. Most cases of partial pattern had predominant involvement of the medial
      dorsal component (82.6%). There was no significant association between teres
      minor atrophy and previous trauma, shoulder instability, osteoarthritis, and
      previous operation. The history of shoulder instability was more frequently found
      in patients with isolated teres minor atrophy (6.4%), compared with the control
      group (2.6%), although the difference was not statistically significant.
      CONCLUSION: Isolated teres minor atrophy may be either complete or partial, and
      the partial pattern may involve either the medial-dorsal or the lateral-ventral
      component of the muscle. The imaging findings of partial pattern teres minor
      atrophy indicate that the two muscle components may have separate innervation.

PMID- 30091010
TI  - Water near its Supercritical Point and at Alkaline pH for the Production of
      Ferric Oxides and Silicates in Anoxic Conditions. A New Hypothesis for the
      Synthesis of Minerals Observed in Banded Iron Formations and for the Related
      Geobiotropic Chemistry inside Fluid Inclusions.
AB  - An alternative hypothesis for the origin of the banded iron formations and the
      synthesis of prebiotic molecules is presented here. I show the importance of
      considering water near its supercritical point and at alkaline pH. It is based on
      the chemical equation for the anoxic oxidation of ferrous iron into ferric iron
      at high-subcritical conditions of water and high pH, that I extract from E-pH
      diagrams drawn for corrosion purposes (Geophysical Research Abstracts Vol 15,
      EGU2013-22 Bassez 2013, Orig Life Evol Biosph 45(1):5-13, Bassez 2015, Procedia
      Earth Planet Sci 17, 492-495, Bassez 2017a, Orig Life Evol Biosph 47:453-480,
      Bassez 2017b). The sudden change in solubility of silica, SiO2, at the critical
      point of water is also considered. It is shown that under these temperatures and
      pressures, ferric oxides and ferric silicates can form in anoxic terrains. No
      FeII oxidation by UV light, neither by oxygen is needed to explain the minerals
      of the Banded Iron Formations. The intervention of any kind of microorganisms,
      either sulfate-reducing, or FeII-oxidizing or O2-producing, is not required. The
      chemical equation for the anoxic oxidation of ferrous iron is applied to the
      hydrolyses of fayalite, Fe2SiO4 and ferrosilite, FeSiO3. It is shown that the BIF
      minerals of the Hamersley Group, Western Australia, and the Transvaal Supergroup,
      South Africa, are those of fayalite and ferrosilite hydrolyses and carbonations.
      The dissolution of crustal fayalite and ferrosilite during water-rock interaction
      needs to occur at T&P just below the critical point of water and in a rising
      water which is undersaturated in SiO2. Minerals of BIFs which can then be ejected
      at the surface from venting arcs are ferric oxide hydroxides, hematite, FeIII
      greenalite, siderite. The greenalite dehydrated product minnesotaite forms when
      rising water becomes supersaturated in SiO2, as also riebeckite and
      stilpnomelane. Long lengths of siderite without ferric oxides neither ferric
      silicates can occur since the exothermic siderite formation is not so much
      dependent in T&P. It is also shown that the H2 which is released during
      hydrolysis/oxidation of fayalite/ferrosilite can lead to components of life, such
      as macromolecules of amino acids which are synthesized from mixtures of (CO, N2,
      H2O) in Sabatier-Senderens/Fischer-Tropsch & Haber-Bosch reactions or microwave
      or gamma-ray excitation reactions. I propose that such geobiotropic synthesis may
      occur inside fluid inclusions of BIFs, in the silica chert, hematite, FeIII
      greenalite or siderite. Therefore, the combination of high-subcritical conditions
      of water, high solubility of SiO2 at these T&P values, formation of CO also at
      these T&P, high pH and anoxic water, leads to the formation of ferric minerals
      and prebiotic molecules in the process of geobiotropy.

PMID- 30091011
TI  - Oncological consequence of emergent resection of perforated colon cancer with
      complete obstruction after stent insertion as a bridge to surgery.
AB  - PURPOSE: Colonic perforation is a life-threatening complication after colonic
      stent insertion as a bridge to surgery for acute obstruction caused by colorectal
      cancer. The oncological consequence of colonic perforation after emergent
      surgical intervention was unknown. The aim of this short communication was to
      investigate whether or not the perforation and emergent surgery had obviously
      impact on the peritoneal recurrence and long-term survival of patients. METHODS:
      Data of the patients who underwent colorectal stenting as a bridge to surgery in
      5 years from 2012 to 2017 was collected by the Endoscopical Surgery Group of
      Hubei. The perforated cases treated by emergent operation were retrospectively
      analyzed. RESULTS: During 5 years from 2012 to 2017, 116 cases of colorectal
      stenting as a bridge to surgery had been performed, and 7 patients had
      perforation after stent placement and treated by emergent surgery, including 1
      case of synchronic liver metastasis treated by one-stage metastasectomy. One of
      the 7 patients died of septic shock after operation, and the remaining patients
      were followed up for 6-60 months. There was no evidence of abdominal implantation
      or extra-abdominal metastasis. CONCLUSION: This small case series implicated that
      colonic perforation after stent insertion for malignant colorectal obstruction
      treated by emergent surgery might not obviously increase the peritoneal
      implantation and metastasis.

PMID- 30091012
TI  - Specialized Care for Women: the Impact of Women's Heart Centers.
AB  - PURPOSE OF THE REVIEW: Cardiovascular disease (CVD) has been and remains the
      leading cause of mortality in women in the United States. For decades, more women
      died every year of CVD compared to men. Heart centers for women (HCW) are
      developed in response to the need for greater patient and physician awareness of
      CVD in women and to conduct sex-specific research in women. Today, many HCW
      provide multispecialty and focused areas of cardiovascular care for women. HCW
      provide their female patients with expertise over the many stages of a woman's
      life. And HCW partner with national organizations to advance research and
      education through specialized and focused care for women. The purpose of this
      review is to review the historical development of heart centers for women and
      discuss the types of care they provide for women. RECENT FINDINGS: Mortality
      rates from cardiovascular disease in women are finally reaching the levels of men
      after decades of focus on awareness, prevention, and evidence-based guideline
      directed care for women. Heart centers for women have evolved to provide
      subspecialty and comprehensive care for women that includes education and
      research. Heart centers for women are partnering with many other disease-based
      and patient advocacy organizations to provide care for all women at all stages of
      life. Alarmingly, there has been increasing CVD mortality in both men and women
      recently.

PMID- 30091013
TI  - Could Peer Support Programs Be a Good Resource for Managing the Unmet Needs of
      Cancer Patients?
AB  - The number of cancer patients has been rapidly increasing, and while there have
      been wide variations, cancer survival rates also improved globally. Despite the
      improved survival rates, supportive care needs of cancer patients have been unmet
      in various domains. The current study aimed to investigate unmet needs that had
      potential to be managed by peer supports according to cancer trajectories. We
      used the comprehensive needs assessment tool in cancer (CNAT) and a modified CNAT
      to evaluate the unmet needs and peer support needs of cancer patients at the
      tertiary hospital of South Korea. Of the 402 participants, 335 (83.3%) needed
      peer support. For patients who had been diagnosed with cancer for more than 5
      years, the highest proportion of peer support needs to unmet supportive care was
      reported in information domain (92.9%). Patients with advanced cancer reported
      peer support needs in the social/religious/spiritual (84.4%) and practical
      domains (81.1%). Most of stomach cancer patients needed peer supports to receive
      information (96.6%). The need for peer supports in the information domain was
      reported highest according to longer survival period and also according to
      advanced cancer stages. The proportion of peer support needs in unmet supportive
      care varied by cancer type. Further interventional studies are needed to
      investigate satisfaction with peer support in specific domains.

PMID- 30091014
TI  - Community Breast Health Education for Immigrants and Refugees: Lessons Learned in
      Outreach Efforts to Reduce Cancer Disparities.
AB  - Community-academic partnerships are vital to address cancer disparities in
      geographic areas with diverse socioeconomic, language, and cultural barriers.
      Regarding breast health, immigrant and refugee women are a particularly
      vulnerable population, with considerably lower mammography rates than most
      communities, including racial and ethnic minorities. To promote health care
      equity in this high-risk population, we developed a community-academic
      partnership (CAP) model to promote breast health education at community faith
      based centers in the city of Milwaukee, WI. In this paper, we describe the
      success of our partnerships, our lessons learned, and future directions.

PMID- 30091015
TI  - A novel human mAb (MERS-GD27) provides prophylactic and postexposure efficacy in
      MERS-CoV susceptible mice.

PMID- 30091016
TI  - The non-canonical NF-kappaB pathway promotes NPC2 expression and regulates
      intracellular cholesterol trafficking.
AB  - Niemann-Pick type C2 (NPC2) is a lysosome luminal protein that functions in
      concert with NPC1 to mediate egress of low-density lipoprotein-derived
      cholesterol from lysosome. The nuclear factor kappa B subunit 2 (NF-kappaB2)
      protein is a component of NF-kappaB transcription factor complex critically
      implicated in immune and inflammatory responses. Here, we report that NF-kappaB2
      regulates intracellular cholesterol transport by controlling NPC2 expression.
      RNAi-mediated disruption of NF-kappaB2, as well as other signaling members of the
      non-canonical NF-kappaB pathway, caused intracellular cholesterol accumulation.
      Blockage of the non-canonical NF-kappaB pathway suppressed NPC2 expression,
      whereas Lymphotoxin beta receptor (LTbetaR) activation or Baff receptor (BaffR)
      stimulation up-regulated the mRNA abundance and protein level of NPC2. Further,
      NF-kappaB2 activated NPC2 transcription through direct binding to its promoter
      region. We also observed cholesterol accumulation in NF-kappaB2-deficient
      zebrafish embryo and NF-kappaB2 mutant mice. Collectively, these data identify a
      regulatory role for the non-canonical NF-kappaB pathway in intracellular
      cholesterol trafficking and suggest a link between cholesterol transport and
      immune system.

PMID- 30091017
TI  - Intractable pneumothorax due to rupture of subpleural rheumatoid nodules: a case
      report.
AB  - BACKGROUND: In rare cases, rheumatoid pleural nodules can rupture into the
      pleural cavity to cause pneumothorax or empyema. We report successful surgical
      treatment of a patient with an intractable secondary pneumothorax due to rupture
      of a subpleural rheumatoid nodule into the pleural cavity. CASE PRESENTATION: A
      75-year-old man with a medical history of rheumatoid arthritis, acute coronary
      syndrome, and diabetes was admitted to our hospital because of left chest pain
      and dyspnea. A chest X-ray and chest computed tomography (CT) scan showed a left
      pneumothorax and several small subpleural nodules with cavitation. Repeated
      pleurodesis via a chest tube failed to improve the pneumothorax, so we decided to
      perform thoracoscopic surgery. Air leakage was detected in the left upper lobe
      where the subpleural nodule was visible on chest CT. Resection of the lesion
      successfully resulted in resolution of the air leakage. The final pathological
      diagnosis of the subpleural nodule was a pulmonary rheumatoid nodule. The patient
      has had no evidence of recurrence of pneumothorax after surgery. CONCLUSIONS: We
      obtained a final pathological diagnosis of a rheumatoid nodule that caused an
      intractable pneumothorax. Pneumothorax associated with rupture of rheumatoid
      nodules in the subpleural cavitary is difficult to treat with thoracoscopic
      surgery as a second-line treatment.

PMID- 30091018
TI  - Cutaneous mucormycosis.

PMID- 30091019
TI  - Abnormalities of thalamus volume and resting state functional connectivity in
      primary insomnia patients.
AB  - Primary insomnia (PI) is associated with deteriorating attention, memory,
      physical and mood complaints. Based on the extensive literature demonstrating the
      critical roles of the thalamus in sleep regulation, we hypothesized that insomnia
      would be associated with functional and structural changes of the thalamus. This
      information is needed to better understand the neural mechanisms of insomnia, and
      would be useful for informing future attempts to alleviate or treat insomnia
      symptoms. Twenty-seven PI patients and 39 matched healthy controls were included
      in the present study. Subcortical volume and resting state functional
      connectivity (RSFC) of thalamus were compared between groups, and the
      relationships between neuroimaging differences and clinical features, including
      the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index Scale
      (ISI), the Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale
      (SDS), also be explored. Compared with the control group, the PI group showed
      significantly reduced volume of thalamus. In addition, several brain regions
      showed reduced RSFC with thalamus in PI patients, such as anterior cingulate
      cortex (ACC), orbitofrontal cortex, hippocampus, caudate and putamen. Correlation
      analyses revealed that, several of these RSFC patterns were negatively correlated
      with PSQI score among PI patients, including thalamic connections with the
      putamen, caudate, hippocampus. Negative correlation was also observed between the
      RSFC strength of right thalamus-right ACC and SDS score in PI patients. This work
      demonstrates the structural and functional abnormalities of the thalamus in PI
      patients that were associated with key clinical features of insomnia. These data
      further highlight the important role of the thalamus in sleep and PI.

PMID- 30091020
TI  - Effects of levodopa therapy on voxel-based degree centrality in Parkinson's
      disease.
AB  - Levodopa therapy is widely recognized as an effective treatment for PD patients,
      however, it is rare of the study looking at effects of levodopa therapy on the
      whole-brain network. This study was to evaluate the effects of levodopa on whole
      brain degree centrality (DC) and seed-based functional connectivity (FC) in PD
      patients. We recruited 26 PD patients and acquired their resting-state fMRI data
      before ('OFF' state) and after ('ON' state) taking a dose of 400 mg levodopa.
      Through constructing the voxel-based brain functional network, we calculated
      distant and local DC and seed-based FC. We found that compared to the healthy
      controls, the PD patients at 'OFF' state showed significantly decreased distant
      DC in several occipital regions and left postcentral gyrus, but increased distant
      DC in the right precentral gyrus, supplementary motor area, and several frontal
      regions. Meanwhile, we detected decreased local DC in the left cuneus and
      bilateral insula but increased local DC in several temporal regions in the PD
      patients at 'OFF' state compared to the controls. Using paired-sample t-tests, we
      found that levodopa effectively normalized the distant DC abnormalities in the PD
      patients particularly in the occipital regions and postcentral gyrus.
      Additionally, compared to 'OFF' state, the PD patients at 'ON' state showed
      decreased FC of the left median cingulate gyrus to brain regions in default mode
      network. The decreased FC of the left median cingulate gyrus to right temporal
      pole was associated with improved UPDRS-III score. This study provided new
      evidence for understanding the neural effects of levodopa therapy on the whole
      brain network in PD patients.

PMID- 30091021
TI  - Mud therapy and skin microbiome: a review.
AB  - Recent findings highlight the role of skin microbiome in modulating immune
      function and inflammatory response. This systematic review aims to investigate
      the effects of muds, already used for the treatment of several rheumatic and
      dermatologic conditions, on skin microbiome. Medline via PubMed, Embase, Cochrane
      Library, and Google Scholar were searched for articles about the effects of
      therapeutic muds on microorganisms of skin microbiome. Five studies were included
      in the review and critically appraised. Limited data suggest that muds have
      various properties that may explain their action on skin microbiome, with
      different effects on commensal and pathogenic microorganisms. Further
      investigation on this topic is needed to better characterize the effects of
      different muds on skin microbiome, thus possibly extending their indications.

PMID- 30091022
TI  - Impact of front line relative dose intensity for methotrexate and comorbidities
      in immunocompetent elderly patients with primary central nervous system lymphoma.
AB  - Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas
      strictly localized to the CNS, occurring mainly in elderly patients with
      comorbidities. Current treatment in fit patients relies on high-dose methotrexate
      and high-dose cytarabine. The aim of this study was to evaluate the efficacy and
      feasibility of this treatment in elderly patients and to assess potential
      prognostic factors associated with survival. We conducted a retrospective study
      in two centers between January 2008 and September 2015 including 35 elderly
      immunocompetent patients who received first-line treatment with high-dose
      methotrexate. With a median follow-up of 19.8 months (range: 1.7-73.4 months),
      median overall survival (OS) was 39.5 months (95% confidence interval (95% CI):
      18.3-60.7) and median progression-free survival (PFS) was 25.8 months (95% CI:
      5.2-46.4). In univariate analysis, administration of high-dose cytarabine and
      achieving a relative dose intensity for methotrexate > 75% were associated with
      increased OS (p = 0.006 and p = 0.003, respectively) and PFS (p = 0.003 and p =
      0.04, respectively) whereas comorbidities, defined by a CIRS-G score >= 8, were
      associated with decreased OS and PFS (p = 0.02 and p = 0.04, respectively). A
      high MSKCC score was associated with decreased OS (p = 0.02). In multivariate
      analysis, administration of high-dose cytarabine was associated with increased OS
      and PFS (p = 0.02 and p = 0.007, respectively). Comorbidities and relative dose
      intensity for methotrexate are important for the prognosis of elderly patients
      with PCNSL. These results must be confirmed in prospective trials.

PMID- 30091023
TI  - Autoimmune manifestations associated with myelodysplastic syndromes.
AB  - Autoimmune disorders (ADs) are encountered in 10 to 20% of patients with
      myelodysplastic syndromes (MDS). Available data suggest that ADs concern more
      often younger patients with higher risk IPSS. MDS subtypes associated with ADs
      are mainly MDS with single lineage dysplasia (MDS-SLD) and MDS with excess blasts
      (MDS-EB). Various types of ADs have been described in association with MDS,
      ranging from limited clinical manifestations to systemic diseases affecting
      multiple organs. Defined clinical entities as vasculitis, connective tissue
      diseases, inflammatory arthritis, and neutrophilic diseases are frequently
      reported; however, unclassified or isolated organ impairment can be seen. In
      general, ADs do not seem to confer worse survival, although certain ADs may be
      associated with adverse outcomes (i.e., vasculitis) or progression of MDS (Sweet
      syndrome). While steroids and immunosuppressive treatment (IST) remain the
      backbone of first-line treatment, increasing evidence suggests that MDS-specific
      therapy as hypomethylating agents, based on their immunomodulatory effect, may be
      effective in treating these complications and for sparing steroids.

PMID- 30091024
TI  - Clinical outcome of granulocyte transfusion therapy for the treatment of
      refractory infection in neutropenic patients with hematological diseases.
AB  - Neutropenic patients with hematological diseases are prone to severe infections.
      Granulocyte transfusion therapy (GTX) is considered as a logical therapeutic
      approach for these problems. However, the efficacy and complications of GTX have
      not been well identified. We retrospectively analyzed the clinical outcomes of
      GTX therapy in our hospital from 2009 to 2015. After 117 granulocyte transfusions
      for 47 patients, 72.3% of these patients' infections were effectively improved,
      and the overall survival rates at 30 and 120 days were 66.0 and 57.5%,
      respectively. The patients who experienced neutrophil recovery within 10 days
      after their therapy initiation had a better response and long-term survival
      period (14/15, 93.3%, vs 20/32, 62.5%, P = 0.037). Higher-dose granulocytes (>
      2.55 * 108/kg) might improve the effective rate of infection in the patients who
      had more than 10 days neutrophil recovery time (17/23, 73.9%, vs 3/9, 33.3%, P =
      0.049). In addition, GTX benefited the patients who suffered from pulmonary
      bacterial infections (16/20, 80%) compared with the bloodstream infection group
      (7/12, 58.3%) and skin or mucous infection group (1/5, 20%). The primary data
      showed that GTX did not affect the incidence of graft-versus-host disease (GVHD)
      and cytomegalovirus viremia when patients received further HSCT treatment.
      Collectively, GTX was an adjunct treatment modality for severely neutropenic
      patients who were likely to experience hematopoietic recovery. More randomized
      trials are needed to verify the efficacy and complications of GTX therapy.

PMID- 30091025
TI  - Does the omission of vincristine in patients with diffuse large B cell lymphoma
      affect treatment outcome?
AB  - The standard treatment for diffuse large B cell lymphoma (DLBCL) is rituximab
      with CHOP (cyclophosphamide, doxorubicin, vincristine (VCR), and prednisone).
      Maintaining high dose intensity of cytotoxic treatment has been associated with
      better outcome but little is known about the role of maintaining VCR. This study
      aimed to answer whether the omission of vincristine due to neurotoxicity affects
      patient outcome. A Swedish cohort of patients primarily treated with curative
      intent for DLBCL or high-grade malignant B cell lymphoma was retrospectively
      analyzed. In total, 541 patients treated between 2000 and 2013 were included.
      Omission of VCR was decided in 95 (17.6%) patients and was more often decided
      during the last three cycles (n = 86, 90.5%). The omission of VCR did not affect
      disease-free or overall survival neither in the whole cohort nor in elderly
      patients. On the contrary, the relative dose intensity of doxorubicin was
      associated with overall survival (p = 0.014). Kidney or adrenal involvement (p =
      0.014) as well as bulky disease (p = 0.037) was found to be associated with worse
      overall survival. According to our results, clinicians can safely decide to omit
      VCR in case of severe neurotoxicity due to VCR but should be aware of the
      importance of giving adequate doses of doxorubicin during treatment given the
      growing body of evidence on the role of dose intensity on survival. Considering
      the association of bulky disease and kidney/adrenal manifestation of lymphoma on
      survival, further studies should focus on whether the treatment options for these
      subgroups need to be individualized.

PMID- 30091026
TI  - Numerical comparative study of five currently used implants for high tibial
      osteotomy: realistic loading including muscle forces versus simplified
      experimental loading.
AB  - BACKGROUND: Many different fixation devices are used to maintain the correction
      angle after medial open wedge high tibial osteotomy (MOWHTO). Each device must
      provide at least sufficient mechanical stability to avoid loss of correction and
      unwanted fracture of the contralateral cortex until the bone heals. In the
      present study, the mechanical stability of following different implants was
      compared: the TomoFix small stature (sm), the TomoFix standard (std), the Contour
      Lock, the iBalance and the second generation PEEKPower. Simplified loading,
      usually consisting of a vertical load applied to the tibia plateau, is used for
      experimental testing of fixation devices and also in numerical studies.
      Therefore, this study additionally compared this simplified experimental loading
      with a more realistic loading that includes the muscle forces. METHOD: Two types
      of finite element models, according to the considered loading, were created. The
      first type numerically simulated the static tests of MOWHTO implants performed in
      a previous experimental biomechanical study, by applying a vertical compressive
      load perpendicularly to the plateau of the osteotomized tibia. The second type
      included muscle forces in finite element models of the lower limb with
      osteotomized tibiae and simulated the stance phase of normal gait. Section forces
      in the models were determined and compared. Stresses in the implants and
      contralateral cortex, and micromovements of the osteotomy wedge, were calculated.
      RESULTS: For both loading types, the stresses in the implants were lower than the
      threshold values defined by the material strength. The stresses in the lateral
      cortex were smaller than the ultimate tensile strength of the cortical bone. The
      implants iBalance and Contour Lock allowed the smallest micromovements of the
      wedge, while the PEEKPower allowed the highest. There was a correlation between
      the micromovements of the wedge, obtained for the simplified loading of the
      tibia, and the more realistic loading of the lower limb at 15% of the gait cycle
      (Pearson's value r = 0.982). CONCLUSIONS: An axial compressive load applied
      perpendicularly to the tibia plateau, with a magnitude equal to the first peak
      value of the knee joint contact forces, corresponds quite well to a realistic
      loading of the tibia during the stance phase of normal gait (at 15% of the gait
      cycle and a knee flexion of about 22 degrees). However, this magnitude of the
      knee joint contact forces overloads the tibia compared to more realistic
      calculations, where the muscle forces are considered. The iBalance and Contour
      Lock implants provide higher rigidity to the bone-implant constructs compared to
      the TomoFix and the PEEKPower plates.

PMID- 30091027
TI  - Dispersion and infectivity of Toxocara canis eggs after passage through chicken
      intestine.
AB  - Toxocariasis is an important, but neglected, worldwide zoonosis. It is considered
      a primarily soil-transmitted disease, but food-borne transmission has been
      associated with the consumption either of raw or undercooked meat of paratenic
      hosts, including birds. Despite the number of experimental studies carried out to
      evaluate the behavior of Toxocara spp. larvae in birds, their role in the
      dispersion of eggs into the environment remains unclear. Thus, this study aimed
      to evaluate the potential of broiler chickens to release Toxocara canis eggs into
      the environment, and the infectivity of eggs after passage through the intestine.
      Forty commercial broiler chickens, aged 60 days, were randomly distributed into
      three groups. Groups 1 (n = 16) and 2 (n = 16) were orally infected with 5000
      embryonated and 5000 unembryonated T. canis eggs, respectively. Group 3 (n = 8)
      served as a control. Following infection, fecal samples from each chicken were
      examined using a centrifuge-sedimentation technique. At 24-h, 72-h, and 7-day
      post-infection (PI), four chickens each from the G1 and G2 groups, and two from
      the G3 group were killed. After euthanasia, the intestinal content and liver were
      collected for recovery of T. canis larvae. Results revealed that broiler chickens
      have the potential to disperse both embryonated and unembryonated T. canis eggs,
      following 2- to 6-h PI. In addition, the eggs shed into the feces of the G2
      birds, after incubation in laboratorial conditions, were infective when they were
      tested in a bioassay using mice. In conclusion, broiler chickens have the
      potential of dispersing Toxocara spp. eggs into the environment and the eggs
      passed through the intestine are infective after being incubated in experimental
      conditions.

PMID- 30091028
TI  - Obituary in Memory of Professor Francis S. Greenspan 1920-2016.

PMID- 30091029
TI  - Effects of Genetic Counselor Self-Disclosure: an Experimental Analog Study.
AB  - The complex nature of self-disclosure poses challenges for genetic counselors in
      clinical practice. We examined the impact of genetic counselor self-disclosure on
      observer perceptions of the counselor. In an online analog study, 123
      participants watched a 3-minute video of a simulated genetic counseling session.
      For half the participants, the video showed the counselor disclosing that she had
      a family medical history similar to the patient (direct personal disclosure). For
      half the participants, the counselor revealed her experience with other patients
      (direct professional disclosure). Half the participants in each video condition
      read that the patient had discovered personal information about the counselor
      during a pre-session web search (indirect personal disclosure); half read that
      the patient learned of the counselor's FAQ webpage for prospective patients
      (indirect professional disclosure). Participants in the direct personal
      disclosure conditions gave higher ratings to the counseling relationship on an
      abbreviated version of the Barrett-Lennard Relationship Inventory and rated
      themselves more likely to see the counselor compared to those in the direct
      professional disclosure conditions. The content of the indirect disclosure
      conditions (personal or professional) had no effect. Brief, direct, verbal
      disclosure of session-relevant personal information by a genetic counselor
      appears to enhance the counselor-patient relationship and increase the likelihood
      of patients returning to the counselor.

PMID- 30091030
TI  - Using Parasitic Load to Measure the Effect of Anthropogenic Disturbance on Vervet
      Monkeys.
AB  - Vervet monkeys, Chlorocebus pygerythrus, thrive in urban areas of KwaZulu-Natal,
      South Africa, and present a suitable model to assess parasitic load as a measure
      of anthropogenic disturbance, such as urbanization. We collected vervet monkey
      faecal samples from four study sites representing a gradient of land use and
      urbanization. We assessed faecal parasites using the faecal flotation method
      calculating eggs per gram and parasite richness. Overall, the more urban vervet
      monkey populations had a significantly higher parasite richness and abundance.
      Our study shows the applicability of using parasite load to measure the effect of
      urbanization on wildlife.

PMID- 30091031
TI  - Skewed Signaling through the Receptor for Advanced Glycation End-Products Alters
      the Proinflammatory Profile of Tumor-Associated Macrophages.
AB  - Tumors are complex tissues composed of variable amounts of both non-cellular
      components (matrix proteins) and a multitude of stromal cell types, which are
      under an active cross-talk with tumor cells. Tumor-associated macrophages (TAMs)
      are the major leukocyte population among the tumor-infiltrating immune cells.
      Once they are infiltrated into tumor stroma they undergo a polarized activation,
      where the M1 and M2 phenotypes represent the two extreme of the polarization
      heterogeneity spectrum. It is known that TAMs acquire a specific phenotype (M2),
      oriented toward tumor growth, angiogenesis and immune-suppression. A growing body
      of evidences supports the presence of tuning mechanisms in order to skew or
      restraint the inflammatory response of TAMs and thus forces them to function as
      active tumor-promoting immune cells. The receptor of advanced glycation end
      products (RAGE) is a member of the immunoglobulin protein family of cell surface
      molecules, being activated by several danger signals and thus signaling to
      promote the production of many pro-inflammatory molecules. Interestingly, this
      receptor is paradoxically expressed in both M1 and M2 macrophages phenotypes.
      This review addresses how RAGE signaling has been drifted away in M2 macrophages,
      and thus taking advantage of the abundance of RAGE ligands at tumor
      microenvironment, particularly HMGB1, to reinforce the supportive M2 macrophages
      strategy to support tumor growth.

PMID- 30091032
TI  - Circumferential suicidal cutting of the lower legs.
AB  - A 69-year-old woman committed suicide by cutting her lower legs with a safety
      razor blade. Autopsy revealed horizontal incised wounds around the circumference
      of the lower legs, 24 cm above the heels, cutting superficial veins on both
      sides, the underlying lower legs muscles, and extending into both lower leg bones
      with associated hematoma formation. Also, there were a large number of
      superficial tentative or "hesitation" cuts ranging from 3 to 6 cm over the lower
      legs. Death was attributed to hemorrhagic shock following injuries to blood
      vessels of the lower legs.

PMID- 30091033
TI  - Antibody Cross-Linking of CD14 Activates MerTK and Promotes Human Macrophage
      Clearance of Apoptotic Neutrophils: the Dual Role of CD14 at the Crossroads
      Between M1 and M2c Polarization.
AB  - Mer receptor tyrosine kinase (MerTK) is key for efficient phagocytosis of
      apoptotic neutrophils (ANs) and homeostasis of IL-10 production by human anti
      inflammatory M2c monocytes/macrophages. We asked whether stimulation of M2c
      surface receptors contributes in turn to MerTK activation. For this purpose,
      human monocytes/macrophages were differentiated under M1, M2a, and M2c polarizing
      conditions. The effects of antibody-mediated cross-linking of M2c receptors
      (i.e., CD14, CD16, CD32, CD163, CD204) on MerTK phosphorylation and phagocytosis
      of ANs were tested. MerTK expression was also studied by flow cytometry and
      western blot in the presence of LPS and in M2c-derived microvesicles (MVs).
      Antibody cross-linking of either CD14 or CD32/FcgammaRII led to Syk activation
      and MerTK phosphorylation in its two distinct glycoforms (175-205 and 135-155
      kDa). Cross-linked CD14 enhanced efferocytosis by M2c macrophages and enabled M1
      and M2a cells to clear ANs efficiently. In M1 conditions, LPS abolished surface
      MerTK expression on CD14bright cell subsets, so disrupting the anti-inflammatory
      pathway. In M2c cells, instead, MerTK was diffusely and brightly co-expressed
      with CD14, and was also detected in M2c macrophage-derived MVs; in these
      conditions, LPS only partially downregulated MerTK on cell surfaces, while the
      smaller MerTK glycoform contained in MVs remained intact. Altogether, cooperation
      between CD14 and MerTK may foster the clearance of ANs by human
      monocytes/macrophages. CD14 stands between M1-related LPS co-receptor activity
      and M2c-related MerTK-dependent response. MerTK interaction with CD32/FcgammaRII,
      its detection in M2c MVs, and the differential localization and LPS
      susceptibility of MerTK glycoforms add further new elements to the complexity of
      the MerTK network.

PMID- 30091034
TI  - Blockade of Aquaporin 4 Inhibits Irradiation-Induced Pulmonary Inflammation and
      Modulates Macrophage Polarization in Mice.
AB  - To investigate the effects of aquaporin 4 (AQP4) inhibitor in irradiation-induced
      pulmonary inflammation in mice. A single dose of 75 Gy was delivered to the left
      lung of mice to induce radiation pneumonitis. For inhibition of AQP4, 200 mg/kg
      of TGN-020 was administered i.p. one time per 2 days post-irradiation. Blockade
      of AQP4 with TGN-020 resulted in the inhibition of inflammatory cell infiltration
      and the downregulation of inflammatory cytokines (IL-6, IL-17, and TGF-beta),
      chemokines (MIP1a and MCP1), fibrosis-related (Col3al and Fn1), and M2 macrophage
      marker (Arg1) post-irradiation. Immunofluorescence staining indicated that there
      was significant fewer M2 macrophage infiltration in the irradiated lung tissues
      from mice treated with TGN-020. Additionally, depletion of macrophages with
      liposome clodronate resulted in alleviated lung injury induced by irradiation.
      Furthermore, adoptive transfer of M1 or M2 macrophages into clodronate-treated
      mice was performed. The results showed that the administration of M2 macrophages
      fully reversed the clodronate-induced beneficial effect on inflammation score,
      thickness, and fibrosis. However, transfer of M1 macrophages only impacted the
      inflammation score and thickness and did not affect lung fibrosis. AQP4 blockade
      alleviated the development and severity of irradiated lung damage. This was
      associated with attenuated infiltration of inflammatory cell, decreased
      production of pro-inflammatory cytokines, and inhibited activation of M2
      macrophages.

PMID- 30091035
TI  - The Role of SIRT1 in Autophagy in Lipopolysaccharide-Induced Mouse Type II
      Alveolar Epithelial Cells.
AB  - Silent mating type information regulation 2 homolog-1 (SIRT1) is involved in a
      wide range of cellular processes because of its role as a deacetylated histone
      and its association with a variety of transcription factors. SIRT1 has essential
      roles in autophagy, including in the formation of autophagic vacuoles and the
      assembly of autophagy-related gene (ATG) protein complexes. The present study
      focused on the role of SIRT1 in autophagy in lipopolysaccharide (LPS)-induced
      mouse type II alveolar epithelial cells (AECII). We designed experiments using
      SIRT1-overexpressing mice and wild-type mice, and AECII were isolated from these
      two types of mouse for in vitro LPS injury trials. Our results suggest that
      levels of the autophagy proteins, Beclin1 and LC3B, as well as those of the
      inflammatory factors, IL-6 and TNF-alpha, were increased in LPS-induced mouse
      AECII, and that SIRT1 protected against damage in mice with acute respiratory
      distress syndrome and in mouse AECII in vitro following LPS treatment.
      Subsequently, we screened multiple inflammatory, apoptotic, and unclassified
      genes (including Atg7), which interacted with SIRT1 in LPS-injured mouse AECII,
      as assessed by mRNA microarray analysis. These results demonstrate that LPS can
      reduce the levels of SIRT1 and ATG7 in vivo and in vitro and indicate that SIRT1
      is involved in autophagy through regulation of ATG7 in AECII in response to LPS.

PMID- 30091036
TI  - Moderate-Intensity Exercise Induces Neurogenesis and Improves Cognition in Old
      Mice by Upregulating Hippocampal Hippocalcin, Otub1, and Spectrin-alpha.
AB  - Exercise increases the levels of neurogenic factors and enhances neurogenesis,
      memory, and learning. However, the molecular link between exercise and
      neurogenesis is not clear. The purpose of this study was to examine the effects
      of exercise intensity on cognitive function and protein expression in the
      hippocampus of old mice. To compare the effects of aerobic exercise intensity on
      cognition in old mice, we exposed 18-month-old mice to low- and moderate
      intensity treadmill exercise for 4 weeks. Moderate-intensity exercise improved
      cognitive function in the old mice, while low-intensity exercise did not. To
      investigate the underlying mechanisms, two-dimensional electrophoresis was used
      to examine protein expression. Using peptide fingerprinting mass spectrometry, we
      identified 19 proteins that were upregulated in the hippocampus following
      exercise training, and seven of these proteins were normalized by the control
      value. Among them, the levels of 14-3-3 zeta and heat shock protein 70, which
      have been shown to be induced by exercise training and related to neurogenesis,
      were dramatically increased by moderate exercise. Hippocalcin, alpha-spectrin,
      ovarian tumor domain-containing ubiquitin aldehyde-binding protein 1 (otub1), mu
      crystallin, serine racemase, and rho GDP dissociation inhibitor 1, which are
      related to neurogenesis, neuroprotection, and synaptic strength, were upregulated
      in the hippocampus by moderate exercise. In addition, we confirmed that
      neurogenic markers, including doublecortin and the neuronal nuclei antigen, and
      hippocalcin, otub1, and spectrin-alpha are potential molecular links between
      hippocampal neurogenesis and exercise in the elderly. Thus, these results showed
      that steady moderate-intensity exercise delayed the declines in cognitive
      function in the elderly through the activation of multiple factors.

PMID- 30091037
TI  - Simultaneous Serial Transverse Enteroplasty (STEP) in Size Mismatch Small Bowel
      Transplantations.
AB  - BACKGROUND: Small bowel transplantation (SBTX) in children receiving larger
      grafts from adults can be challenging because of size mismatch. The aim of the
      present study was to assess whether a simultaneous serial transverse enteroplasty
      (STEP) can address the problem of size mismatch. METHODS: Three different size
      ratio groups between donors and recipients were compared in a porcine model with
      a 14-day follow-up. The groups were size matched, size mismatched (1:3.8 weight
      ratio), and size mismatched + STEP (each n = 8). RESULTS: It was technically
      feasible to simultaneously perform a STEP and SBTX of a mismatched intestinal
      segment. The postoperative clinical course was uneventful. No signs of bleeding,
      leakage, stenosis, or ileus were observed and the intestinal segment was well
      perfused at relaparotomy. Body weight decreased in all groups, but the percentage
      decrease was lowest in the mismatched + STEP group. Vital enterocyte masses were
      similar in all the groups (citrulline levels) and the nutritional status was best
      in the STEP group (transferrin levels, p = 0.04). CONCLUSIONS: We have
      demonstrated that a simultaneous STEP and SBTX procedure is technically feasible
      and clinically useful in overcoming the challenges associated with size
      mismatched SBTX. Our short-term findings justify further investigation in a
      larger series to elucidate the long-term outcomes of this procedure.

PMID- 30091038
TI  - Mental Illness Has a Negative Impact on Weight Loss in Bariatric Patients: a 4
      Year Follow-up.
AB  - BACKGROUND: Mental health disorders are highly prevalent among bariatric surgery
      patients. Bariatric surgery induces weight loss with continuous health
      improvements. However, long-term follow-up data on weight loss and quality of
      life data of patients who have a mental illness after bariatric surgery are
      scarce, and it is not clear whether mental illness is associated with more
      pronounced weight regain. The aim was to investigate the impact of preoperative
      mental illness on the course of long-term weight changes after bariatric surgery.
      METHODS: Patients with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass
      surgery (RYGB) between 2005 and 2013 with a follow-up of at least 3 years were
      included. The study population was divided into two groups: patients with mental
      illness (MI) and patients without (No-MI). Weight loss outcomes over time were
      compared using mixed models up to 4 years after surgery. RESULTS: In total, 254
      patients (RYGB 61.0%, SG 39%) were included. The distribution of baseline
      characteristics was similar between the MI (n = 108) and No-MI groups (n = 146).
      The most prevalent mental illness was depressive disorder (63.9%). In the MI
      group, the percent of total weight loss (%TWL) was significantly smaller over the
      study period. After 36 months, the predicted mean group-difference of %TWL was
      4.6% (95% CI 1.9, 7.2; p = 0.001), and the predicted odds ratio for weight regain
      was 4.9 (95% CI 1.6, 15.1) for patients in the MI group. CONCLUSION: Preoperative
      mental illness leads to lower long-term weight loss and an increased risk of
      weight regain after bariatric surgery.

PMID- 30091039
TI  - Duct-To-Duct Biliary Anastomosis with Removable Internal Biliary Stent During
      Major Hepatectomy Extended to the Biliary Confluence.
AB  - BACKGROUND: Roux-en-Y hepaticojejunostomy (HJ) currently represents the gold
      standard after resection of the biliary confluence. This non-physiological
      reconstruction poses several problems such as repeated cholangitis or stricture
      without conventional endoscopic access. Our aim was to describe and to report
      both feasibility and results of duct-to-duct anastomosis with removable internal
      biliary drain (RIBS) as an alternative technique to the HJ after resection of the
      biliary confluence in patients undergoing major liver resection. METHODS: Between
      January 2014 and January 2018, all patients who underwent a major hepatectomy
      associated with resection of the biliary confluence and reconstruction by duct-to
      duct biliary anastomosis with RIBS were retrospectively included. Patient
      demographics, tumor characteristics, pre- and postoperative outcomes, early and
      late biliary complications, endoscopic complications, and clinical follow-up were
      collected. RESULTS: Twelve patients were included. The operative time was 326 +/-
      45 min (range 240-380 min). There was no postoperative mortality. Only one
      patient experienced biliary anastomotic leakage treated exclusively by
      radiological and endoscopic drainage. Four patients had an asymptomatic stricture
      of the biliary anastomosis detected by endoscopic retrograde
      cholangiopancreatography (ERCP) during the extraction of the RIBS requiring
      iterative dilatation and replacement of the RIBS. Among 21 performed ERCP, no
      complications such as failure of RIBS extraction, duodenal perforation, bleeding
      after sphincterotomy, cholangitis, or pancreatitis were observed. After a mean
      and a median follow-up of respectively 15.0 +/- 14.9 and 8.7 months (range 2.0
      46.1 months), no cholangitis occurred. CONCLUSION: Duct-to-duct biliary
      anastomosis with RIBS insertion after resection of the biliary confluence
      represents a feasible and safe alternative to the HJ.

PMID- 30091040
TI  - Freiburg Neuropathology Case Conference : Tumor of the Mesiotemporal Lobe in a
      Child.

PMID- 30091041
TI  - Stroke Transfer and its Organizational Paradigm : Review of Organizational
      Paradigms and the Impact on Outcome.
AB  - Since the clinical recognition of endovascular therapy (EVT) for stroke treatment
      is recent (2015), some organizational issues, such as the "drip and ship (DS)
      versus mothership (MS)" access to EVT remain unanswered. There is growing
      pressure to guarantee immediate access to EVT with limited human resources and
      infrastructures. As results from prospective studies are missing, a review of the
      existing literature dealing with clinical retrospective studies was carried out.
      Most of the studies did not report a significant difference with respect to the
      adverse effects for patients treated by EVT according to the organizational
      paradigm of care. Several studies did not report a significant difference
      concerning the 3 months functional outcomes regarding the organizational
      paradigm. Only two studies built theoretical models of the best outcomes and
      observed a superiority of the DS only if the door to needle time was less than 30
      min. Waiting for the results of ongoing randomized controlled trials, this review
      of articles presenting patients treated with either MS or DS provides an overview
      but does not emphasize a superiority of a given paradigm; however, it highlights
      the inequalities of access to EVT according to the organization of care in
      different areas.

PMID- 30091042
TI  - Synergism between high hydrostatic pressure and glutaraldehyde for the
      inactivation of Staphylococcus aureus at moderate temperature.
AB  - The sterilization of transplant and medical devices should be effective but not
      detrimental to the structural properties of the materials used. In this study, we
      examined the effectiveness of chemical and physical agents for inactivating
      Staphylococcus aureus, a gram-positive bacterium and important cause of
      infections and biofilm production. The treatment conditions in this work were
      chosen to facilitate their subsequent use with sensitive materials. The effects
      of temperature, high hydrostatic pressure, and glutaraldehyde disinfectant on the
      growth of two strains of S. aureus (ATCC 25923 and BEC 9393) were investigated
      individually and/or in combinations. A low concentration of glutaraldehyde (0.5
      mM), high hydrostatic pressure (300 MPa for 10 min), and moderate temperature (50
      degrees C), when used in combination, significantly potentiated the inactivation
      of both bacterial strains by > 8 orders of magnitude. Transmission electron
      microscopy revealed structural damage and changes in area that correlated with
      the use of pressure in the presence of glutaraldehyde at room temperature in both
      strains. Biofilm from strain ATCC 25923 was particularly susceptible to
      inactivation. The conditions used here provided effective sterilization that can
      be applied to sensitive surgical devices and biomaterials, with negligible
      damage. The use of this experimental approach to investigate other pathogens
      could lead to the adoption of this procedure for sterilizing sensitive materials.

PMID- 30091043
TI  - Process intensification of EB66(r) cell cultivations leads to high-yield yellow
      fever and Zika virus production.
AB  - A live-attenuated, human vaccine against mosquito-borne yellow fever virus has
      been available since the 1930s. The vaccine provides long-lasting immunity and
      consistent mass vaccination campaigns counter viral spread. However, traditional
      egg-based vaccine manufacturing requires about 12 months and vaccine supplies are
      chronically close to shortages. In particular, for urban outbreaks, vaccine
      demand can be covered rarely by global stockpiling. Thus, there is an urgent need
      for an improved vaccine production platform, ideally transferable to other
      flaviviruses including Zika virus. Here, we present a proof-of-concept study
      regarding cell culture-based yellow fever virus 17D (YFV) and wild-type Zika
      virus (ZIKV) production using duck embryo-derived EB66(r) cells. Based on
      comprehensive studies in shake flasks, 1-L bioreactor systems were operated with
      scalable hollow fiber-based tangential flow filtration (TFF) and alternating
      tangential flow filtration (ATF) perfusion systems for process intensification.
      EB66(r) cells grew in chemically defined medium to cell concentrations of 1.6 *
      108 cells/mL. Infection studies with EB66(r)-adapted virus led to maximum YFV
      titers of 7.3 * 108 PFU/mL, which corresponds to about 10 million vaccine doses
      for the bioreactor harvest. For ZIKV, titers of 1.0 * 1010 PFU/mL were achieved.
      Processes were automated successfully using a capacitance probe to control
      perfusion rates based on on-line measured cell concentrations. The use of cryo
      bags for direct inoculation of production bioreactors facilitates pre-culture
      preparation contributing to improved process robustness. In conclusion, this
      platform is a powerful option for next generation cell culture-based flavivirus
      vaccine manufacturing.

PMID- 30091044
TI  - Human fetoplacental arterial and venous endothelial cells are differentially
      programmed by gestational diabetes mellitus, resulting in cell-specific barrier
      function changes.
AB  - AIMS/HYPOTHESIS: An adverse intrauterine environment can result in permanent
      changes in the physiology of the offspring and predispose to diseases in
      adulthood. One such exposure, gestational diabetes mellitus (GDM), has been
      linked to development of metabolic disorders and cardiovascular disease in
      offspring. Epigenetic variation, including DNA methylation, is recognised as a
      leading mechanism underpinning fetal programming and we hypothesised that this
      plays a key role in fetoplacental endothelial dysfunction following exposure to
      GDM. Thus, we conducted a pilot epigenetic study to analyse concordant DNA
      methylation and gene expression changes in GDM-exposed fetoplacental endothelial
      cells. METHODS: Genome-wide methylation analysis of primary fetoplacental
      arterial endothelial cells (AEC) and venous endothelial cells (VEC) from healthy
      pregnancies and GDM-complicated pregnancies in parallel with transcriptome
      analysis identified methylation and expression changes. Most-affected pathways
      and functions were identified by Ingenuity Pathway Analysis and validated using
      functional assays. RESULTS: Transcriptome and methylation analyses identified
      variation in gene expression linked to GDM-associated DNA methylation in 408
      genes in AEC and 159 genes in VEC, implying a direct functional link. Pathway
      analysis found that genes altered by exposure to GDM clustered to functions
      associated with 'cell morphology' and 'cellular movement' in healthy AEC and VEC.
      Further functional analysis demonstrated that GDM-exposed cells had altered actin
      organisation and barrier function. CONCLUSIONS/INTERPRETATION: Our data indicate
      that exposure to GDM programs atypical morphology and barrier function in
      fetoplacental endothelial cells by DNA methylation and gene expression change.
      The effects differ between AEC and VEC, indicating a stringent cell-specific
      sensitivity to adverse exposures associated with developmental programming in
      utero. DATA AVAILABILITY: DNA methylation and gene expression datasets generated
      and analysed during the current study are available at the National Center for
      Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database (
      http://www.ncbi.nlm.nih.gov/geo ) under accession numbers GSE106099 and
      GSE103552, respectively.

PMID- 30091045
TI  - The impact of hip and knee osteoarthritis on the subsequent risk of incident
      diabetes: a population-based cohort study.
AB  - AIMS/HYPOTHESIS: This study examined the relationship between hip/knee
      osteoarthritis and incident diabetes. We hypothesised that hip/knee
      osteoarthritis would be independently related to an increased risk of incident
      diabetes and that this relationship would be due, at least in part, to walking
      difficulty. We also hypothesised a stronger relationship with incident diabetes
      for knee than hip osteoarthritis because of the higher prevalence in the former
      of obesity/the metabolic syndrome. METHODS: A population cohort aged >=55 years
      recruited from 1996 to 1998 was followed through provincial health administrative
      data to 2014. Participants with baseline diabetes were excluded. Hip/knee
      osteoarthritis was defined as swelling, pain or stiffness in any joint lasting 6
      weeks in the past 3 months and indication on a joint homunculus that a hip/knee
      was 'troublesome'. Walking limitation was defined as self-reported difficulty
      standing or walking in the last 3 months (yes/no). Using Cox regressions, we
      examined the relationship of baseline hip/knee osteoarthritis with incident
      diabetes as defined from health administrative data, controlling for age, sex,
      BMI, income, prior hypertension, cardiovascular disease and primary care
      exposure. We tested whether the observed effect was mediated through walking
      limitation. RESULTS: In total, 16,362 participants were included: median age 68
      years and 61% female. Of these, 1637 (10%) individuals met the criteria for hip
      osteoarthritis, 2431 (15%) for knee osteoarthritis and 3908 (24%) for walking
      limitation. Over a median follow-up of 13.5 years (interquartile range 7.3-17.8),
      3539 individuals (22%) developed diabetes. Controlling for confounders, a
      significant relationship was observed between number of hip/knee joints with
      osteoarthritis and incident diabetes: HR for two vs no osteoarthritic hips 1.25
      (95% CI 1.08, 1.44); HR for two vs no osteoarthritic knees 1.16 (95% CI 1.04,
      1.29). From 37% to 46% of this relationship was explained by baseline walking
      limitation. CONCLUSIONS/INTERPRETATION: In a large population cohort aged >=55
      years who were free of diabetes at baseline, and controlling for confounders, the
      presence and burden of hip/knee osteoarthritis was a significant independent
      predictor of incident diabetes. This association was partially explained by
      walking limitation. Increased attention to osteoarthritis and osteoarthritis
      related functional limitations has the potential to reduce diabetes risk.

PMID- 30091046
TI  - The Nfic-osterix pathway regulates ameloblast differentiation and enamel
      formation.
AB  - Enamel makes up the outermost layer of the crown and its hardness protects other
      dental tissues from various stimuli. Enamel cannot be regenerated once damaged
      because ameloblasts are lost during the tooth eruption. Since the ameloblast
      differentiation mechanism is still unknown, further research is essential for
      developing treatments for defective or damaged enamel. Previously, we have
      reported that osteoblast differentiation and bone formation were regulated
      through the runt-related transcription factor 2 (Runx2)-nuclear factor 1-C (Nfic)
      osterix (Osx) pathway where Nfic directly controls Osx expression. This pathway
      regulates odontoblast differentiation and dentin formation as well. The aim of
      this study was to investigate if the same pathway is applicable for ameloblast
      differentiation. Structural enamel defects with disorganized ameloblasts and
      decreased proliferation activity of the cervical loop were observed in Nfic-/-
      mice incisors. Expression of the ameloblast differentiation markers was also
      downregulated significantly in Nfic-/- mice. Real-time PCR analyses suggested
      that Runx2, Nfic, and Osx regulate the expression of ameloblast differentiation
      markers, where Runx2 is upstream of Nfic, and Nfic controls Osx expression.
      Therefore, we suggest the Runx2-Nfic-Osx pathway as one of the key factors that
      regulate ameloblast differentiation.

PMID- 30091049
TI  - Response to Cognitive outcome following glioma surgery.

PMID- 30091047
TI  - Role of Angio-Embolization for Renal Cell Carcinoma.
AB  - PURPOSE OF REVIEW: To provide the technical aspects of, clinical indications for,
      status of the current literature on, and emerging concepts in trans-arterial
      embolization (TAE) for renal cell carcinoma. RECENT FINDINGS: TAE has been
      evaluated in several retrospective series as a neoadjuvant therapy prior to
      surgical resection of RCC to reduce tumor vascularity and minimize intra
      operative blood loss. TAE has also been examined retrospectively as a neoadjuvant
      therapy prior to the percutaneous ablation of RCC to reduce blood loss and
      procedural complications. TAE can potentially palliate symptoms of RCC such as
      pain and hematuria. Trans-arterial chemoembolization and trans-arterial
      radioembolization are emerging concepts for RCC. Although there have been no
      prospective, randomized trials demonstrating improved clinical or oncologic
      outcomes from TAE for patients with RCC, several retrospective studies have shown
      encouraging results.

PMID- 30091050
TI  - Treatment of cavernous malformations in supratentorial eloquent areas: experience
      after 10 years of patient-tailored surgical protocol.
AB  - BACKGROUND: Eloquent area surgery has become safer with the development of
      intraoperative neurophysiological monitoring and brain mapping techniques.
      However, the usefulness of intraoperative electric brain stimulation techniques
      applied to the management and surgical treatment of cavernous malformations in
      supratentorial eloquent areas is still not proven. With this study, we aim to
      describe our experience with the use of a tailored functional approach to treat
      cavernous malformations in supratentorial eloquent areas. METHODS: Twenty
      patients harboring cavernous malformations located in supratentorial eloquent
      areas were surgically treated. Individualized functional approach, using
      intraoperative brain mapping and/or neurophysiological monitoring, was utilized
      in each case. Eleven patients underwent surgery under awake conditions;
      meanwhile, nine patients underwent asleep surgery. RESULTS: Total resection was
      achieved in 19 cases (95%). In one patient, the resection was not possible due to
      high motor functional parenchyma surrounding the lesion tested by direct cortical
      stimulation. Ten (50%) patients presented transient neurological worsening. All
      of them achieved total neurological recovery within the first year of follow-up.
      Among the patients who presented seizures, 85% achieved seizure-free status
      during follow-up. No major complications occurred. CONCLUSIONS: Intraoperative
      electric brain stimulation techniques applied by a trained multidisciplinary team
      provide a valuable aid for the treatment of certain cavernous malformations. Our
      results suggest that tailored functional approach could help surgeons in adapting
      surgical strategies to prevent patients' permanent neurological damage.

PMID- 30091051
TI  - Cognitive outcome following glioma surgery.

PMID- 30091052
TI  - 5-Aminolevulinic acid fluorescence-guided surgery for spinal cord melanoma
      metastasis: a technical note.
AB  - BACKGROUND: According to our research, just few studies described 5
      Aminolevulinic acid (5-ALA) use for spinal injuries resection. 5-ALA is known to
      be especially useful in certain spinal tumor entities such as meningiomas,
      ependymomas, hemangiopericytomas, and metastasis of central nervous system
      primary tumors. In contrast, 5-ALA has limited value in other histopathological
      tumoral entities, as neurinomas and carcinoma metastasis. METHOD: We describe a
      microsurgical resection of a spinal cord melanoma through fluorescence-guided
      technique using 5-ALA in a 36-year-old man. RESULTS: Strong 5-ALA tumor
      enhancement was evidenced, resulting in gross-total resection. CONCLUSION: To our
      knowledge, this is the first case of nonglial intramedullary metastasis with 5
      ALA positive staining. We believe that this tool, 5-ALA, could aid in the
      resection, identification, and differentiation of medullary metastasis.

PMID- 30091053
TI  - Lack of effective translational regulation of PLD expression and exosome
      biogenesis in triple-negative breast cancer cells.
AB  - Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer
      that is difficult to treat since cells lack the three receptors (ES, PR, or HER)
      that the most effective treatments target. We have used a well-established TNBC
      cell line (MDA-MB-231) from which we found evidence in support for a
      phospholipase D (PLD)-mediated tumor growth and metastasis: high levels of
      expression of PLD, as well as the absence of inhibitory miRs (such as miR-203)
      and 3'-mRNA PARN deadenylase activity in these cells. Such findings are not
      present in a luminal B cell line, MCF-7, and we propose a new miR*PARN*PLD node
      that is not uniform across breast cancer molecular subtypes and as such TNBC
      could be pharmacologically targeted differentially. We review the participation
      of PLD and phosphatidic acid (PA), its enzymatic product, as new "players" in
      breast cancer biology, with the aspects of regulation of the tumor
      microenvironment, macrophage polarization, regulation of PLD transcripts by
      specific miRs and deadenylases, and PLD-regulated exosome biogenesis. A new
      signaling miR*PARN*PLD node could serve as new biomarkers for TNBC abnormal
      signaling and metastatic disease staging, potentially before metastases are able
      to be visualized using conventional imaging.

PMID- 30091054
TI  - Corticotropin-releasing factor (CRF) system localization in human fetal heart.
AB  - OBJECTIVE: The corticotropin-releasing factor (CRF) family consists of the
      neuropeptides CRF, Ucn I, II and III and the binding sites CRFR1, CRFR2 and CRF
      BP. It regulates stress response and the homeostasis of an organism. In this
      study, we examined the presence of the CRF system in the human hearts of normal
      and pathological fetuses. DESIGN: Heart tissues from 40 archival human fetuses
      were divided into Group A (without pathology, 'normal'), Group B (with
      chromosomal abnormalities) and Group C (with congenital disorders).
      Immunohistochemistry was used to localize the CRF system. Results correlated to
      gestational trimester and pathology. RESULTS: Immunoreactivity for all antigens
      was found in cardiac myocytes of all groups, in almost all samples, except Ucn
      III which was present in almost half of the fetuses of Groups B and C and was not
      detected at all in Group A. Ucn III was more often present during the earlier
      stage of development (<21 weeks) and in fetuses with congenital disorders. In a
      fetus diagnosed with heart pathology, all but Ucn III antigens were also present.
      CONCLUSIONS: We localized a complete CRF system in the human fetal heart and
      correlated the presence of Ucn III to development and pathology. More studies are
      needed to verify and clarify the exact role of the CRF system in the human fetal
      heart.

PMID- 30091055
TI  - Deep learning-based detection and classification of geographic atrophy using a
      deep convolutional neural network classifier.
AB  - PURPOSE: To automatically detect and classify geographic atrophy (GA) in fundus
      autofluorescence (FAF) images using a deep learning algorithm. METHODS: In this
      study, FAF images of patients with GA, a healthy comparable group and a
      comparable group with other retinal diseases (ORDs) were used to train a multi
      layer deep convolutional neural network (DCNN) (1) to detect GA and (2) to
      differentiate in GA between a diffuse-trickling pattern (dt-GA) and other GA FAF
      patterns (ndt-GA) in FAF images. 1. For the automated detection of GA in FAF
      images, two classifiers were built (GA vs. healthy/GA vs. ORD). The DCNN was
      trained and validated with 400 FAF images in each case (GA 200, healthy 200, or
      ORD 200). For the subsequent testing, the built classifiers were then tested with
      60 untrained FAF images in each case (AMD 30, healthy 30, or ORD 30). Hereby,
      both classifiers automatically determined a GA probability score and a normal FAF
      probability score or an ORD probability score. 2. To automatically differentiate
      between dt-GA and ndt-GA, the DCNN was trained and validated with 200 FAF images
      (dt-GA 72; ndt-GA 138). Afterwards, the built classifier was tested with 20
      untrained FAF images (dt-GA 10; ndt-GA 10) and a dt-GA probability score and an
      ndt-GA probability score was calculated. For both classifiers, the performance of
      the training and validation procedure after 500 training steps was measured by
      determining training accuracy, validation accuracy, and cross entropy. RESULTS:
      For the GA classifiers (GA vs. healthy/GA vs. ORD), the achieved training
      accuracy was 99/98%, the validation accuracy 96/91%, and the cross entropy
      0.062/0.100. For the dt-GA classifier, the training accuracy was 99%, the
      validation accuracy 77%, and the cross entropy 0.166. The mean GA probability
      score was 0.981 +/- 0.048 (GA vs. healthy)/0.972 +/- 0.439 (GA vs. ORD) in the GA
      image group and 0.01 +/- 0.016 (healthy)/0.061 +/- 0.072 (ORD) in the comparison
      groups (p < 0.001). The mean dt-GA probability score was 0.807 +/- 0.116 in the
      dt-GA image group and 0.180 +/- 0.100 in the ndt-GA image group (p < 0.001).
      CONCLUSION: For the first time, this study describes the use of a deep learning
      based algorithm to automatically detect and classify GA in FAF. Hereby, the
      created classifiers showed excellent results. With further developments, this
      model may be a tool to predict the individual progression risk of GA and give
      relevant information for future therapeutic approaches.

PMID- 30091056
TI  - [Modified neck-lengthening osteotomy after Morscher in children and adolescents].
AB  - OBJECTIVE: Growth disorders (e. g. caused by congenital hip dislocation, Perthes
      disease or bacterial coxitis) often lead to an infantile deformity of the
      proximal femur with a shortened femoral neck and displaced grater trochanter. In
      1988, Morscher and Buess described a femoral neck lenghtening osteotomy for
      treatment of adults. For the first time, we show a modification of this osteotomy
      for children and adolescents with a locking plate system. The aim is to restore
      the normal anatomy of the femoral neck and biomechanics of the proximal femur.
      INDICATIONS: All symptomatic deformities of the proximal femur with a shortened
      femoral neck and a proximal displacement of the greater trochanter.
      CONTRAINDICATIONS: Bacterial coxitis within the last two years; elevated
      infections parameters. Acetabular dysplasia with a lack of femoral head
      containment. SURGICAL TECHNIQUE: Two osteotomies: one at the level of the greater
      trochanter to transfer it. The second osteotomy at the level of the distal
      femoral neck. Stabilization with a locking plate system (LCP Pediatric Hip Plate
      130 degrees , Synthes, Oberdorf, Switzerland). POSTOPERATIVE MANAGEMENT: Full
      weight bearing to a body weight of 55 kg; partial weight bearing with a body
      weight >55 kg for 6 weeks. RESULTS: No intraoperative or postoperative
      complications were observed in 5 female patients (mean age 11.67 years). After a
      follow-up of 6-12 weeks, none of the patients presented a Trendelenburg's sign.
      After 3-6 months, full range of motion was possible.

PMID- 30091057
TI  - p47phox-/- Chronic Granulomatous Disease Patient with Incomplete Kawasaki
      Disease.

PMID- 30091058
TI  - Statistical Optimization of the Sol-Gel Electrospinning Process Conditions for
      Preparation of Polyamide 6/66 Nanofiber Bundles.
AB  - Polymeric nanofibers are widely studied in the textile industry since with them,
      it is possible to get a great variety of functionalities. In this paper,
      polyamide 6/66 (PA 6/66) solutions at different concentrations (12, 17, and 22%
      wt.) were made, to get nanofibers through the basic electrospinning process which
      were characterized by scanning electron microscope (SEM) and productivity.
      Afterwards, nanofiber bundles were produced using the electrospinning sol-gel
      process, which were characterized by SEM and tensile test. From the results of
      statistical optimization based on one-way analysis of variance (ANOVA) with post
      hoc Tukey HSD, it was found that nanofiber bundles with higher productivity (1.39
      +/- 0.15 mg/min), draw ratio (9.0 +/- 1.2), and tensile strength (29.64 +/- 7.40
      MPa) were obtained with a 17% concentration. Finally, a thermal characterization
      through differential scanning calorimetry (DSC) was done, finding evidence of a
      Tg and Tm reduction in the nanofibers in relation to PA 6/66 pellets and
      nanofiber bundles.

PMID- 30091059
TI  - Emergency Laparoscopic Gastrectomy for Intraperitoneal Ruptured Gastric
      Gastrointestinal Stromal Tumor.

PMID- 30091060
TI  - Effects of the percentage of air/water in spray on the efficiency of tooth
      ablation with erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG)
      laser irradiation.
AB  - We aimed at examining the effects of a percentage of air/water in spray on the
      cutting efficiency of Er,Cr:YSGG laser for enamel and dentin. The intensity and
      frequency of irradiation were 3.0 W and 20 Hz for the enamel surface and 2.0 W
      and 20 Hz for the dentin surface, respectively. Flattened surfaces of enamel and
      dentin were irradiated at nine points for approximately 1 s under various
      percentages of air/water in spray using Er,Cr:YSGG laser. A high-speed video
      microscope was used to record each laser irradiation on the tooth surface. A slow
      video image was used to count the number of water micro-explosions yielded on the
      tooth surface during laser irradiation. A surface roughness tester was used to
      measure the depth of the dimple prepared with laser irradiation on each specimen.
      Each individual depth of dimple was divided by the number of water micro
      explosions (pulse). This allowed for the calculation of the cutting depth per
      pulse. Following laser irradiation, several representative specimens were
      observed using an SEM. Two-way ANOVA was used as the statistical analysis. This
      revealed that there was no significant effect of the percentage of air/water in
      spray on the cutting depth for enamel surface (p > 0.05). On the contrary, a
      significant effect was observed in air-ratio for dentin cutting (p < 0.05). Both
      enamel and dentin were characterized by the presence of rough surfaces, as shown
      by the SEM images of the dimples. The percentage of air/water in spray was not
      significantly effective in laser cutting for enamel. Air-percentage was
      significantly effective in laser cutting for dentin.

PMID- 30091061
TI  - Effect of atorvastatin on dyslipidemia and carotid intima-media thickness in
      children with refractory nephrotic syndrome: a randomized controlled trial.
AB  - BACKGROUND: Dyslipidemia is an important cardiovascular risk factor in steroid
      resistant nephrotic syndrome (SRNS). Efficacy of statins for treatment of
      hyperlipidemia in children with SRNS is unclear. METHODS: This prospective,
      randomized, double-blind, placebo-controlled, parallel-group clinical trial
      enrolled 30 patients with SRNS, aged 5-18 years, with serum low-density
      lipoprotein cholesterol (LDL-C) levels between 130 and 300 mg/dl, to receive a
      fixed dose of atorvastatin (n = 15, 10 mg/d) or placebo (n = 15) by block
      randomization in a 1:1 ratio. Primary outcome was change in serum LDL-C at 12
      months. Change in levels of other lipid fractions, carotid intima-media thickness
      (cIMT), flow-mediated dilation (FMD) of the brachial artery, and adverse events
      were also evaluated. RESULTS: At the end of 12 months, atorvastatin was not
      superior to placebo in reducing plasma LDL-C levels, median percentage reduction
      15.8% and 9.5% respectively, in atorvastatin and placebo arms (n = 14 in each; P
      = 0.40). Apolipoprotein B levels significantly declined with atorvastatin in
      modified intention-to-treat analysis (P = 0.01) but not in the per-protocol
      analysis. There was no significant effect on other lipid fractions, cIMT and FMD.
      Adverse events were similar between groups. Change in serum albumin was
      negatively associated with change in serum LDL-C, very low-density lipoprotein
      cholesterol, total cholesterol, triglyceride, and apolipoprotein B (P < 0.001),
      irrespective of receiving atorvastatin, age, gender, body mass index, and serum
      creatinine. CONCLUSIONS: Atorvastatin, administered at a fixed daily dose of 10
      mg, was not beneficial in lowering lipid levels in children with SRNS; rise in
      serum albumin was associated with improvement in dyslipidemia.

PMID- 30091062
TI  - Preparation, Characterization and Pharmacokinetics Evaluation of the Compound
      Capsules of Ibuprofen Enteric-Coated Sustained-Release Pellets and Codeine
      Phosphate Immediate-Release Pellets.
AB  - The objective of this study was to prepare ibuprofen enteric-coated sustained
      release pellets (IB-SRPs) and codeine phosphate immediate-release pellets (CP
      IRPs) to play a synergistic role in analgesia. The pellets were developed by
      extrusion-spheronization and fluidized bed coating technology. The single-factor
      investigation was used to determine the optimal prescription and process. The
      sustained-release membrane of IB-SRPs was water-insoluble ethyl cellulose (EC),
      triethyl citrate (TEC) was used as plasticizer, and hydroxypropyl methylcellulose
      (HPMCP) was chose as porogen. Besides, the immediate-release layer of CP-IRPs was
      gastric-soluble coating film. The ibuprofen and codeine phosphate compound
      capsules (IB-CP SRCs) were prepared by IB-SRPs and CP-IRPs packed together in
      capsules with the optimum doses of 200 and 13 mg, respectively. The prepared
      pellets were evaluated by scanning electron microscopy and dissolution test.
      Pharmacokinetic studies in beagle dogs indicated that the optimized IB-CP SRCs
      had smaller individual differences and better reproducibility comparing with
      commercial available tablets. Additionally, IB-CP SRCs achieved consistency with
      in vivo and in vitro tests. Therefore, IB-CP SRCs could play a great role in
      rapid and long-term analgesic.

PMID- 30091063
TI  - Research Progress of Raman Spectroscopy in Drug Analysis.
AB  - Raman spectroscopy is a spectroscopic analysis technique that enables rapid
      qualitative and quantitative detection based on inelastic collision and Raman
      scattering intensity. This review detailed the generation principle, instrument
      composition, influencing factors, and common classifications of Raman spectrum.
      Furthermore, it summarized and forecast the research progress of Raman
      spectroscopy in the field of drug analysis simultaneously over the past decade,
      including the identification of active pharmaceutical ingredients (APIs),
      qualitative and quantitative studies of pharmaceutical preparations, detection of
      illicit drugs, the identification of Chinese herbal medicines, and the
      combination with other technologies. The development of Raman spectroscopy in
      other fields is additionally summarized.

PMID- 30091064
TI  - Build better bones with exercise (B3E pilot trial): results of a feasibility
      study of a multicenter randomized controlled trial of 12 months of home exercise
      in older women with vertebral fracture.
AB  - : We pilot-tested a trial of home exercise on individuals with osteoporosis and
      spine fracture. Our target enrollment was met, though it took longer than
      expected. Participants stayed in the study and completed the exercise program
      with no safety concerns. Future trials should expand the inclusion criteria and
      consider other changes. PURPOSE: Osteoporotic fragility fractures create a
      substantial human and economic burden. There have been calls for a large
      randomized controlled trial examining the effect of exercise on fracture
      incidence. The B3E pilot trial was designed to evaluate the feasibility of a
      large trial examining the effects of home exercise on individuals at high risk of
      fracture. METHODS: Community-dwelling women >= 65 years with radiographically
      confirmed vertebral compression fractures were recruited at seven sites in Canada
      and Australia. We randomized participants in a 1:1 ratio to a 12-month home
      exercise program or equal attention control group, both delivered by a
      physiotherapist (PT). Participants received six PT home visits in addition to
      monthly phone calls from the PT and a blinded research assistant. The primary
      feasibility outcomes of the study were recruitment rate (20 per site in 1 year),
      retention rate (75% completion), and intervention adherence rate (60% of weeks
      meeting exercise goals). Secondary outcomes included falls, fractures and adverse
      events. RESULTS: One hundred forty-one participants were recruited; an average of
      20 per site, though most sites took longer than anticipated. Retention and
      adherence met the criteria for success: 92% of participants completed the study;
      average adherence was 66%. The intervention group did not differ significantly in
      the number of falls (IRR 0.97, 95% CI 0.58 to 1.63) or fragility fractures (OR
      1.11, 95% CI 0.60 to 2.05) compared to the control group. There were 18 serious
      adverse events in the intervention group and 12 in the control group. CONCLUSION:
      An RCT of home exercise in women with vertebral fractures is feasible but
      recruitment was a challenge. Suggestions are made for the conduct of future
      trials.

PMID- 30091065
TI  - Decreasing trend of bone mineral density in US multiethnic population: analysis
      of continuous NHANES 2005-2014.
AB  - : Studies examining recent bone mineral density (BMD) trends in the US population
      are limited. In our study, we found that age-adjusted mean BMD among US men and
      women was stable from 2005 to 2010, but then declined in 2013-2014. We also
      explored factors associated with decreasing BMD in recent years. INTRODUCTION:
      Osteoporosis prevalence in the USA declined between 1988 and 2006, while the
      declining trend in hip fracture may have plateaued in 2013-2014. We aimed to
      examine whether there has been a corresponding change in BMD trajectory for the
      US population. METHODS: Continuous National Health and Nutrition Examination
      Survey (NHANES) data from 2005-2006 to 2013-2014 were analyzed to examine BMD
      trends among US men and women aged 30 years and older and among different
      race/ethnicity subgroups. ANOVA and Bonferroni adjustments were used to examine
      the differences in mean BMD, and multiple linear regressions adjusting for
      potential confounding effects were employed to examine BMD trends. RESULTS: After
      age standardization, the mean BMD of the femur neck for the first three NHANES
      cycles was stable (all p > 0.1) in both men and women, but significantly
      decreased in 2013-2014, from 0.864 g/cm2 to 0.846 g/cm2 (p = 0.0025) in men and
      from 0.789 to 0.771 g/cm2 (p = 0.03) in women. The overall mean femur neck BMD in
      2013-2014 was significantly lower than that in earlier survey cycles in both men
      and women, even after adjusting for multiple covariates, including age, race,
      physical activity, previous fracture, BMI, and other variables. Similar results
      were observed in subgroup analyses of race and sensitivity analyses. CONCLUSIONS:
      Age-adjusted mean BMD decreased in 2013-2014 in both men and women, and this
      significant decrease was also observed in sensitivity and subgroup analyses. The
      decreased BMD in 2013-2014 still remained significant even after being adjusted
      for multiple potentially confounding effects.

PMID- 30091066
TI  - Causes and treatment outcomes of revision surgery after open reduction and
      internal fixation of tibial plateau fractures.
AB  - PURPOSE: Treatment of a tibial plateau fracture (TPF) remains controversial and
      is generally challenging. Many authors report good results after conventional
      open reduction and internal fixation in TPF, but complications still occur. This
      study analyzed causes and outcomes of revision surgery for TPF. The usefulness of
      a flow chart for revision surgery in TPF was also evaluated. METHODS: We reviewed
      all patients who underwent more than two operations for a TPF between 2008 and
      2015. Finally, 24 cases were selected and retrospectively investigated. The
      medial tibial plateau angle and proximal posterior tibial angle were
      radiologically evaluated. The American Knee Society Score (AKSS), Western Ontario
      and McMaster Universities Osteoarthritis Index (WOMAC), range of motion (ROM),
      and bone union time were investigated after surgery. RESULTS: Revision surgery
      for infection was performed in eight cases, for nonunion in six cases, for
      posttraumatic arthritis (with total knee arthroplasty) in six cases, and for
      other reasons in four cases. The mean clinical AKSS at final follow-up was 87.3
      +/- 5.3 (range, 75-95), the functional AKSS was 81.9 +/- 5.5 (range, 70-90), the
      WOMAC score was 9.9 +/- 3.1 (range, 5-16), the flexion ROM was 119.8 +/- 16.5
      degrees  (range, 100-150 degrees ), and the extension ROM was 2.5 +/- 3.3 degrees
      (range, 0-10 degrees ). CONCLUSIONS: Although complications cannot be avoided in
      some cases, good clinical outcomes are possible when patients are divided
      according to the presence or absence of infection, with selection of appropriate
      revision surgery as shown in the flow chart. If an infection is present,
      treatment should be based on the presence or absence of bone union. If there is
      no infection, treatment should be based on the presence or absence of nonunion,
      post-traumatic arthritis, malunion, or immediate post-operative malreduction.

PMID- 30091067
TI  - An evidence-based etiology study of synovial cyst of knee cruciate ligament: a
      real or pseudo-cyst.
AB  - PURPOSE: Synovial cyst of knee cruciate ligament (SCKCL) is a rare condition but
      can cause severe knee pain. The understanding of its etiology is relatively poor.
      This current study aimed to elucidate the pathogenesis of SCKCL based on a series
      of histo- and cytopathological examination. METHODS: Ten SCKCL patients who
      underwent arthroscopy were enrolled, among five patients claimed past knee
      injury. Hematoxylin & eosin staining was conducted to the cyst wall tissue
      sections and Papanicolaou staining to the cyst fluid smear. Prussian blue
      staining was employed to both the wall section and fluid smear.
      Immumohistochemical staining for mesothelial cells (MC), epithelial cells (CK),
      vascular endothelial cells (CD31), monocytes (CD68), and hematogenous stem cells
      (CD117) were taken to elucidate the possible involvement of various cell types in
      the development of SCKCL. RESULTS: No erythrocyte was discovered in the fluid;
      however, Prussian blue stained hemosiderin particles were found in the cyst wall
      and fluid, suggesting past hemorrhage in all patients. Abundant lymphocytes and
      plasmocytes were observed in the cyst wall and fluid. In addition, the cyst
      lining was infiltrated with abundant CD68(+) monocytes while only few MC(+)
      mesothelial cells were sporadically observed in four samples. The cyst submucosa
      was also diffused with abundant CD68(+) monocytes and proliferated capillaries
      stained with CD31. CD117-positve hematogenous stem cells were sporadically
      observed in eight specimens. CONCLUSION: Our findings provided evidence that
      SCKCL is not a mature synovial cyst but rather an inflammatory pseudo-cyst. It
      may have resulted from past minor hemorrhage and intra-ligament chronic
      inflammation.

PMID- 30091068
TI  - Morphometry evaluations of cervical osseous endplates based on three dimensional
      reconstructions.
AB  - PURPOSE: Accurate and comprehensive data on cervical endplates is essential for
      developing and improving cervical devices. However, current literature on
      vertebral disc geometry is scarce or not suitable. The aim of this study was to
      obtain quantitative parameters of cervical endplates and provide morphometric
      references for designing cervical devices. METHODS: In this study, 19 human
      cervical spine cadaveric specimens were considered. Employing a reverse
      engineering system, the surface information of each endplate was recorded in
      digital cloud and then 3D reconstructed. A measurement protocol that included
      three sagittal and three frontal surface curves was developed. The information of
      surface curves and endplate concavity were obtained and analyzed. The parametric
      equations of endplate surfaces were deduced based on coordinates of landmarks,
      and the reliability was verified. RESULTS: The cervical endplate surface had a
      trend that to be transversely elongated gradually. The concavity depths of
      inferior endplates (1.88 to 2.13 mm) were significantly larger than those of
      superior endplates (0.62 to 0.84 mm). The most-concave points in inferior
      endplates were concentrated in the central portion, while always located in post
      median region in superior endplates. CONCLUSION: These results will give
      appropriate guidelines to design cervical prostheses without sacrificing valuable
      bone stock. The parametric equations applied for generating surface profile of
      cervical endplates may provide great convenience for subsequent studies.

PMID- 30091069
TI  - The Relationship between Dietary, Serum and Hair Levels of Minerals (Fe, Zn, Cu)
      and Glucose Metabolism Indices in Obese Type 2 Diabetic Patients.
AB  - The aim of this study was to assess the levels of Zn, Fe and Cu in the serum and
      hair, and dietary intake of type 2 diabetic patients and their association with
      glucose and lipid indices. The study was conducted on 62 people aged 40-78 years
      (31 diabetic patients and 31 healthy subjects, who were the control group). The
      content of trace elements in the hair and serum was analysed with the AAS method.
      The serum insulin, HbA1c, glucose, total cholesterol and triacylglycerol
      concentrations were measured by means of RIA, HPLC and colorimetric methods,
      respectively. The diabetic patients were found to have significantly higher
      dietary iron intake, higher hair Fe and lower serum Zn concentrations than the
      non-diabetic subjects, while the hair Zn and Cu contents were comparable in both
      groups. The serum Zn and Cu levels of the diabetic subjects were negatively
      correlated with the serum glucose, the serum Zn and Cu/Zn ratio was inversely
      correlated with the serum total cholesterol and the serum insulin level was
      positively associated with the hair Cu/Zn ratio. The results of this study
      indicate that the trace element status (Zn, Fe, Cu), as reflected in the blood
      serum and hair, may be disturbed due to metabolic derangement occurring in
      diabetes.

PMID- 30091070
TI  - A Brief Overview from the Physiological and Detrimental Roles of Zinc Homeostasis
      via Zinc Transporters in the Heart.
AB  - Zinc (mostly as free/labile Zn2+) is an essential structural constituent of many
      proteins, including enzymes in cellular signaling pathways via functioning as an
      important signaling molecule in mammalian cells. In cardiomyocytes at resting
      condition, intracellular labile Zn2+ concentration ([Zn2+]i) is in the nanomolar
      range, whereas it can increase dramatically under pathological conditions,
      including hyperglycemia, but the mechanisms that affect its subcellular
      redistribution is not clear. Therefore, overall, very little is known about the
      precise mechanisms controlling the intracellular distribution of labile Zn2+,
      particularly via Zn2+ transporters during cardiac function under both
      physiological and pathophysiological conditions. Literature data demonstrated
      that [Zn2+]i homeostasis in mammalian cells is primarily coordinated by Zn2+
      transporters classified as ZnTs (SLC30A) and ZIPs (SLC39A). To identify the
      molecular mechanisms of diverse functions of labile Zn2+ in the heart, the recent
      studies focused on the discovery of subcellular localization of these Zn2+
      transporters in parallel to the discovery of novel physiological functions of
      [Zn2+]i in cardiomyocytes. The present review summarizes the current
      understanding of the role of [Zn2+]i changes in cardiomyocytes under pathological
      conditions, and under high [Zn2+]i and how Zn2+ transporters are important for
      its subcellular redistribution. The emerging importance and the promise of some
      Zn2+ transporters for targeted cardiac therapy against pathological stimuli are
      also provided. Taken together, the review clearly outlines cellular control of
      cytosolic Zn2+ signaling by Zn2+ transporters, the role of Zn2+ transporters in
      heart function under hyperglycemia, the role of Zn2+ under increased oxidative
      stress and ER stress, and their roles in cancer are discussed.

PMID- 30091071
TI  - Inflated Clinical Evaluations: a Comparison of Faculty-Selected and
      Mathematically Calculated Overall Evaluations Based on Behaviorally Anchored
      Assessment Data.
AB  - OBJECTIVE: This retrospective study compared faculty-selected evaluation scores
      with those mathematically calculated from behaviorally anchored assessments.
      METHODS: Data from 1036 psychiatry clerkship clinical evaluations (2012-2015) was
      reviewed. These clinical evaluations required faculty to assess clinical
      performance using 14 behaviorally anchored questions followed by a faculty
      selected overall evaluation. An explicit rubric was included in the overall
      evaluation to assist the faculty in interpreting their 14 assessment responses.
      Using the same rubric, mathematically calculated evaluations of the same
      assessment responses were generated and compared to the faculty-selected
      evaluations. RESULTS: Comparison of faculty-selected to mathematically calculated
      evaluations revealed that while the two methods were reliably correlated (Cohen's
      kappa = 0.314, Pearson's coefficient = 0.658, p < 0.001), there was a notable
      difference in the results (t = 24.5, p < 0.0001). The average faculty-selected
      evaluation was 1.58 (SD = 0.61) with a mode of "1" or "outstanding," while the
      mathematically calculated evaluation had an average of 2.10 (SD = 0.90) with a
      mode of "3" or "satisfactory." 51.0% of the faculty-selected evaluations matched
      the mathematically calculated results: 46.1% were higher and 2.9% were lower.
      CONCLUSIONS: Clerkship clinical evaluation forms that require faculty to make an
      overall evaluation generate results that are significantly higher than what would
      have been assigned solely using behavioral anchored assessment questions.
      Focusing faculty attention on assessing specific behaviors rather than overall
      evaluations may reduce this inflation and improve validity. Clerkships may want
      to consider removing overall evaluation questions from their clinical evaluation
      tools.

PMID- 30091072
TI  - Theoretical investigations of the chemical bonding in MM'O2 clusters (M, M' = Be,
      Mg, Ca).
AB  - Motivated by the known stability of the somewhat unusual Be2O2 rhombus, which
      features a short Be-Be distance but no direct metal-metal bonding, we investigate
      the nature of the bonding interactions in the analogous clusters MM'O2 (M, M' =
      Be, Mg, Ca). CCSD/cc-pVTZ and CCSD(T)/cc-pVQZ calculations, amongst others, are
      used to determine optimized geometries and the dissociation energies for
      splitting the MM'O2 clusters into metal oxide monomers. The primary tools used to
      investigate the chemical bonding are the analysis of domain-averaged Fermi holes,
      including the generation of localized natural orbitals, and the calculation of
      appropriate two- and three-center bond indices. Insights emerging from these
      various analyses concur with earlier studies of M2O2 rhombic clusters in that
      direct metal-metal bonding was not observed in the MM'O2 rings whereas weak three
      center (3c) bonding was detected in the MOM' moieties. In general terms, these
      mixed MM'O2 clusters exhibit features that are intermediate between those of M2O2
      and M'2O2, and the differences between the M and M' atoms appear to have little
      impact on the overall degree of 3c MOM' bonding. Graphical abstract Bonding
      situation in MM'O2 clusters (M, M' = Be, Mg, Ca).

PMID- 30091073
TI  - Characterization and adsorption capacity of potassium permanganate used to modify
      activated carbon filter media for indoor formaldehyde removal.
AB  - This study examined the effect of potassium permanganate (KMnO4)-modified
      activated carbon for formaldehyde removal under different face velocities and
      different initial formaldehyde concentrations in building environment. We chose
      the coconut shell activated carbon due to their high density and purity.
      Moreover, they have a clear environmental advantage over coal-based carbons,
      particularly in terms of acidification potential. The chemical properties were
      characterized by FTIR to show the functional groups, EDS to calculate each
      component of their energy bands to know how the ratio is. Also, the morphology of
      the surface was examined with scanning electron microscopy (SEM). The BET
      determines specific surface area, pore size, and pore volume. It was found that
      where the initial formaldehyde concentration and the face velocity are low,
      adsorption capacity is high. The adsorption isotherms of formaldehyde on modified
      activated carbon are well fitted by both Langmuir and Freundlich equations. The
      rate parameter for the pseudo-first-order model, pseudo-second-order model, and
      intraparticle diffusion model was compared. The correlation coefficient of pseudo
      second-order kinetic model (0.999 > R2 > 0.9548) is higher than the coefficient
      of pseudo-first-order kinetic model (0.5785 < R2 < 0.8755) and intraparticle
      diffusion model (0.9752 < R2 < 0.9898). Thus, pseudo-second-order kinetic model
      is more apposite to discuss the adsorption kinetic in this test, and the overall
      rate of the modified activated carbon adsorption process appears to be influenced
      by more than one step that is both the intraparticle diffusion model and membrane
      diffusion.

PMID- 30091074
TI  - First evaluation of floating microplastics in the Northwestern Adriatic Sea.
AB  - Plastic pollution in the marine environment is becoming a problem of global
      concern, and the Mediterranean is believed to be one of the worst affected
      regional seas. The present study presents data on floating microplastics in the
      Northwestern Adriatic Sea in order to evaluate the possible contribution of two
      significant potential sources: the lagoon of Venice and the Po River. Samples
      were collected in March and April 2014 along two transects located off
      Pellestrina Island (Venice) and the Po Delta, each consisting of four sampling
      stations at 0.5, 3, 10, and 20 km from the shoreline. Microplastics were
      quantified and classified according to their colors and shapes and analyzed by
      micro-attenuated total reflection-FT-IR. Microplastics were found in all samples,
      albeit with high spatial and temporal variability. The highest concentrations
      were observed in March at the offshore station of the Pellestrina transect (10.4
      particles m-2) and the two landward stations off the Po Delta (2.1 and 4.3
      particles m-2), highlighting the influence of various factors, such as surface
      circulation and river discharges, in determining specific accumulation patterns.
      The most common polymers were polyethylene and polypropylene, and most of the
      particles were secondary microplastics (83.5%). The patchy distribution of
      microplastics observed in the study area is driven by hydrodynamic and
      meteorological factors acting on short time scales.

PMID- 30091075
TI  - Facile preparation of microscale hydrogel particles for high efficiency
      adsorption of bisphenol A from aqueous solution.
AB  - Hydrogel microparticles (HMPs) were synthesized via reverse emulsion/UV light
      polymerization and employed as adsorbents for removing bisphenol A (BPA) from
      aqueous solution. Results demonstrated the smooth surface of HMPs, with particle
      size ranging from 137 to 535 MUm. Functional groups, including -OH, C-O, C=O, and
      C-H, are all involved in BPA adsorption confirmed by FTIR. Effect of solution pH,
      contact time, and initial BPA concentration on adsorption process was examined.
      The adsorption capacity was found pH independent below pH 8.0 and decreased when
      pH values greater than 8.0. The maximum adsorption capacity of the HMPs for BPA
      was 174.77 mg/g. The adsorption process achieved an equilibrium state within 30
      min by the pseudo-second-order kinetic rather than the other kinetic models and
      was fitted well with the Freundlich linear isotherm model. Also, the obtained
      isotherms reflected the formation of S-type isotherm curve according to Giles's
      classification. The BPA loaded on the HMPs could be totally regenerated by
      methanol/dimethylsulfoxide and can be used for five cycles maintaining 100% of
      adsorption capacity. When the HMPs were applied for the treatment of spiked real
      surface water, excellent results were also achieved indicating the high
      efficiency and potential of the adsorbent.

PMID- 30091076
TI  - Equilibrium study of binary mixture biosorption of Cr(III) and Zn(II) by
      dealginated seaweed waste: investigation of adsorption mechanisms using X-ray
      photoelectron spectroscopy analysis.
AB  - The alginate extraction residue (RES) from the Brazilian Sargassum filipendula
      was successfully employed as biosorbent in this binary equilibrium study,
      revealing a greater affinity and selectivity for Cr(III) than for Zn(II).
      Experimental results also revealed that the process is of endothermic nature and
      well adjusted by Langmuir-Freundlich binary model. The X-ray photoelectron
      spectroscopy (XPS) analysis revealed that coordination with hydroxyl groups of
      RES prevailed in Cr removal, followed by carboxyl-metal complexation. As far as
      Zn(II) is concerned, ion exchange with carboxylate groups of RES was the largest
      contributor. Nevertheless, scanning electron microscopy coupled with Fourier
      transform infrared spectroscopy indicated the participation of sulfate functions
      in a minor degree.

PMID- 30091077
TI  - Interpreting competitive adsorption of arsenate and phosphate on nanosized iron
      (hydr)oxides: effects of pH and surface loading.
AB  - Arsenate and phosphate have similar properties due to their electrochemical
      structures, but their environmental impacts are unique. The abundance and
      competition of arsenate and phosphate determine their bioavailability and
      leachability; thus, it is essential to understand their fate in the soil
      environment. In this study, the effects of pH and surface loading on the
      competitive adsorption of arsenate and phosphate on four iron (hydr)oxides were
      evaluated by employing the Langmuir isotherm, competitive sorption ratio (CSR),
      and competition effect (CE). The stability and transformation of the iron
      (hydr)oxides were also assessed. Various adsorption patterns were observed in the
      single and mixed treatments by controlling the addition of oxyanions, pH, surface
      loading, and type of iron (hydr)oxides. Arsenate was preferentially adsorbed at a
      low pH, whereas phosphate showed the opposite trend. The CEAs(V),P(V) was close
      to zero at low surface density (no competition) and sequentially changed to
      negative or positive values with increasing surface density, indirectly
      indicating the sequential development of promotive and competitive effects.
      Transformation in goethite was identified at a high pH with the presence of
      oxyanions, except that no transformation was observed upon the addition of
      oxyanions and with pH change. However, the stability of the iron (hydr)oxides
      decreased at a low pH and with the presence of phosphate, arsenate, or both. The
      hematite showed a significant promotive effect regardless of the pH. Our study
      revealed that the pH, surface loading, and type of iron (hydr)oxides are
      intercorrelated and simultaneously affect the adsorption characteristics of
      oxyanions and the stability of iron (hydr)oxides.

PMID- 30091078
TI  - Stability of mercury on a novel mineral sulfide sorbent used for efficient
      mercury removal from coal combustion flue gas.
AB  - Nano-structured zinc sulfide (Nano-ZnS) has been demonstrated to be a promising
      alternative to activated carbon (AC) for controlling mercury emission from coal
      combustion flue gas. The ultimate fate of the mercury-laden Nano-ZnS after
      mercury capture is mostly disposed in landfill with fly ashes. Thus, the
      stability of mercury adsorbed on the Nano-ZnS is of considerable significance in
      the secured disposal of fly ash after mercury removal and in the commercial
      application of the Nano-ZnS sorbent for removal of mercury from coal combustion
      flue gas. In this work, a modified toxicity characteristic leaching procedure
      (TCLP) was conducted to evaluate the leachability of mercury on the Nano-ZnS. The
      effects of leachate pH value, leaching time, liquid-to-solid ratio, and acid rain
      types on mercury leaching from the mercury-laden Nano-ZnS were systematically
      investigated. The TCLP results show that the concentration of mercury in leachate
      was far below the safe limit (200 MUg/L) as imposed by the US Environmental
      Protection Agency (EPA) for classifying a material as a hazardous waste. All the
      key parameters that generally affected metal leaching rate exhibited slight
      effect on mercury leaching from the mercury-laden Nano-ZnS. Leaching tests at
      various highly severe conditions resulted in less than 0.01% mercury leaching
      from the mercury-laden Nano-ZnS. Sequential selective extraction tests
      demonstrated that mercury sulfide (HgS) was the dominant adsorption product on
      the Nano-ZnS, which guaranteed the excellent stability of mercury adsorbed on the
      Nano-ZnS. Graphic abstract ?.

PMID- 30091079
TI  - Waste-cleaning waste: synthesis of ZnO porous nano-sheets from batteries for dye
      degradation.
AB  - This paper describes a clean approach of waste-cleaning waste. Two-dimensional
      (2D) ZnO porous nano-sheets were synthesized from end-of-life zinc-carbon
      batteries via a simple homogeneous precipitation-calcination route, and the as
      synthesized product was applied as photocatalyst for the purpose of
      photodegradation of methylene blue/MB aqueous solution under UV-Vis irradiation.
      Precipitation at ambient temperature resulted in the formation of the crystalline
      phase of zinc hydroxide nitrate hydrate [Zn5(OH)8(NO3)2(H2O)2], which was then
      transformed to ZnO through calcination. FE-SEM studies revealed the resulting ZnO
      had the morphology of porous nano-sheets with thickness of up to 100 nm. The
      photocatalytic activity tests proved that the batteries-derived ZnO porous nano
      sheets can be a promising candidate for photodegradation of organic pollutant in
      industrial waste water. The results presented here confirm a possibility of
      utilization waste batteries as a resource of photodegrading MB in wastewater
      treatment, hereby an opportunity to deliver environmental benefits. Graphical
      abstract.

PMID- 30091080
TI  - Correction to: Population-Based Analysis of Cluster Headache-Associated Genetic
      Polymorphisms.
AB  - The original version of this article unfortunately contained mistakes in author
      group section.

PMID- 30091081
TI  - Long-Term Effects of Iloperidone on Cerebral Serotonin and Adrenoceptor Subtypes.
AB  - The atypical antipsychotic drug iloperidone has high affinity for a wide range of
      neurotransmitter receptors, including serotonin and adrenoceptors. We examined
      the long-term effects of multiple doses of iloperidone (0.5, 1.5, or 5 mg/kg) on
      serotonin (5-HT) 5-HT1A, 5-HT2A receptor subtypes, and adrenoceptors alpha1 and
      alpha2 subtypes. Rats received daily intraperitoneal injections of different
      doses of iloperiodone or vehicle for 4 weeks. Receptor autoradiography quantified
      the levels of 5-HT and adrenoceptors in medial prefrontal cortex (MPC),
      dorsolateral frontal cortex (DFC), caudate putamen (CPu), nucleus accumbens
      (NAc), and hippocampal CA1 (HIP-CA1) and CA3 (HIP-CA3) regions. Four weeks of
      iloperidone treatment significantly and dose-dependently increased 5-HT1A and
      decreased 5-HT2A receptors in the MPC and DFC. Higher doses of iloperidone (1.5
      and 5 mg/kg) increased 5-HT1A and decreased 5-HT2A receptors in HIP-CA1 and HIP
      CA3 regions. In addition, repeated iloperidone treatment produced significant
      increases in alpha1- and alpha2-adrenoceptors in MPC, DFC, HIP-CA1, and HIP-CA3
      regions. No changes in 5-HT and adrenoceptors were observed in other brain
      regions examined. These results suggest that long-term iloperidone treatment
      exerts region- and dose-specific effects on forebrain 5-HT and adrenoceptors,
      which may contribute to its therapeutic benefits in improving positive and
      negative symptoms of schizophrenia as well as maintaining a benign safety
      profile.

PMID- 30091082
TI  - Plasma FGF23 does not rise during physical exercise as a physiological model of
      sympathetic activation.

PMID- 30091083
TI  - The impact of heart failure and chronic obstructive pulmonary disease on
      mortality in patients presenting with breathlessness.
AB  - BACKGROUND: Differentiating heart failure from chronic obstructive pulmonary
      disease (COPD) in a patient presenting with breathlessness is difficult but may
      have implications for outcome. We investigated the prognostic impact of diagnoses
      of COPD and/or heart failure in consecutive patients presenting to a secondary
      care clinic with breathlessness. METHODS: In patients with left ventricular
      systolic dysfunction (LVSD) by visual estimation, N-terminal pro B-type
      natriuretic peptide (NTproBNP) levels and spirometry were evaluated (N = 4986).
      Heart failure was defined as either LVSD worse than mild (heart failure with
      reduced ejection fraction) or LVSD mild or better and raised NTproBNP levels (>
      400 ng/L) (heart failure with normal ejection fraction). COPD was defined as
      forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) ratio <
      0.7. The primary outcome was all-cause mortality. RESULTS: 1764 (35%) patients
      had heart failure alone, 585 (12%) had COPD alone, 1751 (35%) had heart failure
      and COPD, and 886 (18%) had neither. Compared to patients with neither diagnosis,
      those with COPD alone [hazard ratio (HR) = 1.84 95% confidence interval (CI) 1.40
      2.43], heart failure alone [HR = 4.40 (95% CI 3.54-5.46)] or heart failure and
      COPD [HR = 5.44 (95% CI 4.39-6.75)] had a greater risk of death. COPD was not
      associated with increased risk of death in patients with heart failure on a
      multivariable analysis. CONCLUSION: While COPD is associated with increased risk
      of death compared to patients with neither heart failure nor COPD, it has a
      negligible impact on prognosis amongst patients with heart failure.

PMID- 30091084
TI  - Subclinical hypothyroidism and the development of heart failure: an overview of
      risk and effects on cardiac function.
AB  - The prevalence of subclinical hypothyroidism (SCH) ranges from 5 to 15% of the
      general population. However, it remains controversial if SCH warrants life-long
      thyroxine replacement therapy. Patients with a thyroid-stimulating hormone (TSH)
      level > 10 mIU/L have a higher risk of developing heart failure with reduced
      ejection fraction as compared to subjects with normal thyroid function. However,
      abnormally high TSH levels could also be connected with an overall lower
      metabolic rate and better survival in elderly subjects. The potential mechanisms
      responsible for diastolic dysfunction of the left ventricle (LV) in SCH are
      connected with endothelial dysfunction and arterial stiffness, inflammatory state
      and are driven by TSH apoptosis-derived microparticles. The impact of SCH on LV
      systolic function is more controversial, and it is connected not only with
      cardiac remodelling but also with predisposition of patients with SCH to the
      conditions leading to heart failure. This review presents an overview of
      processes in the context of potential benefits of thyroxine supplementation
      therapy.

PMID- 30091085
TI  - A prospective, multi-center cohort study: investigating the ability of warfarin
      treated patients to predict their INR.
AB  - BACKGROUND: In practice, warfarin-treated patients may share insight regarding
      their international normalized ratio (INR) value before it is measured. The
      accuracy and potential utility of these predictions have not been evaluated.
      OBJECTIVE: To (1) test how accurately patients can predict their INR; (2)
      identify demographic factors associated with their ability to predict their INR
      accurately; and (3) identify demographic factors associated with the patient's
      INR being in the therapeutic range. METHODS: A prospective, multi-center cohort
      study enrolled patients from eight anticoagulation clinics in Iowa. Inclusion
      criteria were: age >= 18 years, warfarin use >= 60 days, INR goal of 2.0-3.0, and
      expected warfarin use > 6 months. Subjects completed a data collection form
      during enrollment and before each INR measurement. Data included demographics, a
      set of medication taking beliefs and practices, self-reported adherence, past INR
      values, INR prediction and reason(s) for the prediction. RESULTS: There were 87
      subjects enrolled with 372 INR measurements. The mean (SD) number of INRs per
      subject was 4.3 (1.8). Thirty percent of subjects reported they could tell when
      their INR is out of goal range. Patients predicted that 90.5% of their INRs would
      be within goal range, although only 65.5% of INRs were therapeutic. Patients
      correctly predicted a low INR as low or high INR as high in only 9.4% of out of
      range instances. A set of demographic characteristics and medication beliefs were
      not associated with prediction accuracy or percentage of INR measurements in
      range (PINRR). Most patients did not give a reason for their predicted result.
      For those that did, the most common factor was perceived stability at current
      dose. CONCLUSION: While some patients believed they could predict when their INR
      was out of range, only few were able to do so. Most patients assumed a
      therapeutic INR and missed when their INR was high or low. Patients should be
      advised against modifying their warfarin dose without consulting the provider
      that manages their therapy. TRIAL REGISTRATION: ClinicalTrials.gov number, NCT
      02764112.

PMID- 30091086
TI  - Detecting computer-generated random responding in questionnaire-based data: A
      comparison of seven indices.
AB  - With the development of online data collection and instruments such as Amazon's
      Mechanical Turk (MTurk), the appearance of malicious software that generates
      responses to surveys in order to earn money represents a major issue, for both
      economic and scientific reasons. Indeed, even if paying one respondent to
      complete one questionnaire represents a very small cost, the multiplication of
      botnets providing invalid response sets may ultimately reduce study validity
      while increasing research costs. Several techniques have been proposed thus far
      to detect problematic human response sets, but little research has been
      undertaken to test the extent to which they actually detect nonhuman response
      sets. Thus, we proposed to conduct an empirical comparison of these indices.
      Assuming that most botnet programs are based on random uniform distributions of
      responses, we present and compare seven indices in this study to detect nonhuman
      response sets. A sample of 1,967 human respondents was mixed with different
      percentages (i.e., from 5% to 50%) of simulated random response sets. Three of
      the seven indices (i.e., response coherence, Mahalanobis distance, and person
      total correlation) appear to be the best estimators for detecting nonhuman
      response sets. Given that two of those indices-Mahalanobis distance and person
      total correlation-are calculated easily, every researcher working with online
      questionnaires could use them to screen for the presence of such invalid data.

PMID- 30091087
TI  - Development of a questionnaire survey to evaluate lower limb function of patients
      with knee osteoarthritis.
AB  - This study aimed to develop a self-questionnaire index relevant to lower limb
      functional assessment reflecting clinical symptoms and activity restrictions
      associated with activities of daily living (ADL) for patients with knee
      osteoarthritis. This cross-sectional study enrolled patients with knee
      osteoarthritis (Kellgren/Lawrence grade >= 1). Participants evaluated clinical
      symptoms and activity restrictions using self-reported questionnaires.
      Radiographic evaluation, knee joint range of motion (ROM), and lower limb muscle
      strength were assessed. Associations between clinical symptoms, activity
      restrictions, and knee and hip joint function were evaluated using multiple and
      logistic regression analysis. Overall, 142 participants were included in the
      final analysis. Patients with knee pain while rising from a chair had lower knee
      and hip extension strength (knee extension beta = - 0.28; 95% confidence interval
      (CI), - 0.41 to - 0.14; P < 0.0001; hip extension beta = - 0.26; 95% CI, - 0.42
      to - 0.08; P = 0.0034), and restricted knee extension ROM (odds ratio [OR] =
      2.17; 95% CI, 1.02-4.63; P = 0.041). Patients with knee pain during stair
      climbing, turning or who were unable to stand on one leg without external support
      had reduced hip abduction muscle strength (beta = - 0.17; 95% CI, - 0.27 to -
      0.07; P = 0.0008). Patients with knee pain while rising from a chair or stepping
      showed more severe knee joint degeneration on radiographic evaluation (OR = 3.26;
      95% CI, 1.11-10.91; P = 0.03). The self-questionnaire index reflected clinical
      symptoms and activity restrictions associated with ADL and was significantly
      associated with lower limb function in individuals with knee osteoarthritis.

PMID- 30091089
TI  - Challenges in the Application of Synthetic Biology Toward Synthesis of Commodity
      Products by Cyanobacteria via "Direct Conversion".
AB  - Cyanobacterial direct conversion of CO2 to several commodity chemicals has been
      recognized as a potential contributor to support the much-needed sustainable
      development of human societies. However, the feasibility of this "green
      conversion" hinders on our ability to overcome the hurdles presented by the
      natural evolvability of microbes. The latter may result in the genetic
      instability of engineered cyanobacterial strains leading to impaired
      productivity. This challenge is general to any "cell factory" approach in which
      the cells grow for multiple generations, and based on several studies carried out
      in different microbial hosts, we could identify that three distinct strategies
      have been proposed to tackle it. These are (1) to reduce microbial evolvability
      by decreasing the native mutation rate, (2) to align product formation with cell
      growth/fitness, and, paradoxically, (3) to efficiently reallocate cellular
      resources to product formation by uncoupling it from growth. The implementation
      of either of these strategies requires an advanced synthetic biology toolkit.
      Here, we review the existing methods available for cyanobacteria and identify
      areas of focus in which specific developments are still needed. Furthermore, we
      discuss how potentially stabilizing strategies may be used in combination leading
      to further increases of productivity while ensuring the stability of the
      cyanobacterial-based direct conversion process.

PMID- 30091088
TI  - Efficient formation of inert Bi-213 chelates by tetraphosphorus acid analogues of
      DOTA: towards improved alpha-therapeutics.
AB  - BACKGROUND: The recently growing interest in targeted alpha-therapy (TAT) calls
      for improvement of the labelling chemistry of the corresponding radionuclides.
      213BiIII is a short-lived alpha emitter which emits only one alpha particle in
      its decay chain. Hence, it might be safer in application than other respective
      nuclides, such as 223Ra or 225Ac, because no alpha-emitting daughters are
      released upon recoil. We investigated cyclen derivatives with phosphorus
      containing pendant arms regarding their suitability for 213Bi labelling. RESULTS:
      The concentration dependency of 213Bi labelling at 25  degrees C and 95  degrees
      C was determined for DOTP, DOTPH, DOTPEt, and DOTPI, as well as for DOTA and CHX
      A"-DTPA for comparison. The labelling efficiency of the phosphorus-containing
      ligands was at least comparable to CHX-A"-DTPA and exceeded that of DOTA. DOTP
      was most efficient, requiring chelator concentrations for labelling which were
      approx. two orders of magnitude lower than those required for CHX-A"-DTPA, both
      at 25  degrees C and 95  degrees C. The 213Bi complexes of phosphorus ligands
      furthermore showed a higher stability against demetallation (> 96% of intact
      complex after 120-min incubation in plasma were found for DOTP, DOTPH, and
      DOTPEt, compared to 85% for DOTA and 76% for CHX-A"-DTPA). CONCLUSION: Cyclen
      derivatives bearing four N-methylenephosphonic or -phosphinic acid substituents,
      e.g., DOTP, are capable of complexing the alpha-emitting radionuclide 213BiIII
      with higher efficiency and in-vitro stability than the current gold standards
      DOTA and CHX-A"-DTPA.

PMID- 30091090
TI  - Transporters Related to Stress Responses and Their Potential Application in
      Synechocystis sp. PCC 6803.
AB  - Cyanobacteria are autotrophic prokaryotes that can perform oxygenic
      photosynthesis. The conversion of light and carbon dioxide into green fuels and
      chemicals has drawn considerable interest, and several dozen products have been
      successfully synthesized in genetically engineered cyanobacteria. However, during
      cultivation, cyanobacterial cells are typically exposed to various stresses from
      the environment, such as acid, salt and metal stresses, as well as from the end
      products they synthesize, such as ethanol, butanol, and 3-hydroxypropionic acid
      (3-HP). These stresses hinder the accumulation of biomass and the production of
      chemicals or biofuels in cyanobacteria. Thus, improving the ability of
      cyanobacterial cells to resist stress can potentially enhance the robustness of
      the cyanobacterial chassis and the final yield of the target products. Toward
      this goal, research has been performed to explore the mechanisms by which
      cyanobacteria respond to various environmental perturbations and product
      toxicity. Among these mechanisms, transporters are membrane proteins involved in
      the transportation of ions, small molecules, or macromolecules across the
      membrane, and they have been reported to be involved in the response to common
      stresses in many organisms. Thus, engineering transporter-encoding genes may be a
      promising solution to increase the resistance of the cells against biotic and
      abiotic stresses. This chapter focuses on recent progress on the use of
      transporters related to stress responses in the model cyanobacterium
      Synechocystis sp. PCC 6803 and presents an updated review of their functions in
      stress regulation and their potential application in future chassis
      modifications.

PMID- 30091091
TI  - Discovery and Application of Stress-Responsive sRNAs in Cyanobacteria.
AB  - Bacterial small regulatory RNAs (sRNAs) are noncoding molecules with a typical
      length of 50-300 nt. In recent years, sRNAs have drawn notable attention due to
      their participation in various bacterial biological processes, such as plasmid
      control, viral replication, bacterial virulence, and quorum sensing. In addition,
      there has been a gradual realization that sRNAs play important roles in the
      response to various stress perturbations. Gram-negative cyanobacteria are
      autotrophic prokaryotes that perform oxygenic photosynthesis, which makes them
      promising renewable chassis for the production of green fuels and chemicals as an
      alternative to the traditional biomass-based "microbial cell factory."
      Nevertheless, the survival and growth of cyanobacteria are affected by multiple
      stressors derived from the environment and from the end products; these organisms
      synthesize, limiting the potential applications of cyanobacteria-based
      biotechnology. Given the importance of sRNAs in metabolic regulation, the
      identification of cyanobacterial sRNAs related to stress responses could be vital
      for further improving the stress tolerance of cyanobacterial chassis. Toward this
      goal, recent studies have described the discovery and functional characterization
      of a series of sRNAs related to stress responses, including responses to
      oxidative stress, salt, nutrient starvation, and ethanol and 1-butanol stress
      conditions. In this chapter, we critically review recent efforts to identify
      cyanobacterial sRNAs involved in stress responses and their potential
      applications for modifying cyanobacterial tolerance.

PMID- 30091092
TI  - Photoresponse Mechanism in Cyanobacteria: Key Factor in Photoautotrophic Chassis.
AB  - As the oldest oxygenic photoautotrophic prokaryotes, cyanobacteria have
      outstanding advantages as the chassis cell in the research field of synthetic
      biology. Cognition of photosynthetic mechanism, including the photoresponse
      mechanism under high-light (HL) conditions, is important for optimization of the
      cyanobacteria photoautotrophic chassis for synthesizing biomaterials as
      "microbial cell factories." Cyanobacteria are well-established model organisms
      for the study of oxygenic photosynthesis and have evolved various acclimatory
      responses to HL conditions to protect the photosynthetic apparatus from
      photodamage. Here, we reviewed the latest progress in the mechanism of HL
      acclimation in cyanobacteria. The subsequent acclimatory responses and the
      corresponding molecular mechanisms are included: (1) acclimatory responses of
      PSII and PSI; (2) the degradation of phycobilisome; (3) induction of the
      photoprotective mechanisms such as state transitions, OCP-dependent non
      photochemical quenching, and the induction of HLIP family; and (4) the regulation
      mechanisms of the gene expression under HL.

PMID- 30091093
TI  - Production of Industrial Chemicals from CO2 by Engineering Cyanobacteria.
AB  - As photosynthetic prokaryotes, cyanobacteria can directly convert CO2 to organic
      compounds and grow rapidly using sunlight as the sole source of energy. The
      direct biosynthesis of chemicals from CO2 and sunlight in cyanobacteria is
      therefore theoretically more attractive than using glucose as carbon source in
      heterotrophic bacteria. To date, more than 20 different target chemicals have
      been synthesized from CO2 in cyanobacteria. However, the yield and productivity
      of the constructed strains is about 100-fold lower than what can be obtained
      using heterotrophic bacteria, and only a few products reached the gram level. The
      main bottleneck in optimizing cyanobacterial cell factories is the relative
      complexity of the metabolism of photoautotrophic bacteria. In heterotrophic
      bacteria, energy metabolism is integrated with the carbon metabolism, so that
      glucose can provide both energy and carbon for the synthesis of target chemicals.
      By contrast, the energy and carbon metabolism of cyanobacteria are separated.
      First, solar energy is converted into chemical energy and reducing power via the
      light reactions of photosynthesis. Subsequently, CO2 is reduced to organic
      compounds using this chemical energy and reducing power. Finally, the reduced CO2
      provides the carbon source and chemical energy for the synthesis of target
      chemicals and cell growth. Consequently, the unique nature of the cyanobacterial
      energy and carbon metabolism determines the specific metabolic engineering
      strategies required for these organisms. In this chapter, we will describe the
      specific characteristics of cyanobacteria regarding their metabolism of carbon
      and energy, summarize and analyze the specific strategies for the production of
      chemicals in cyanobacteria, and propose metabolic engineering strategies which
      may be most suitable for cyanobacteria.

PMID- 30091094
TI  - Cyanobacterial Enzymes for Bioalkane Production.
AB  - Cyanobacterial biosynthesis of alkanes is an attractive way of producing
      substitutes for petroleum-based fuels. Key enzymes for bioalkane production in
      cyanobacteria are acyl-ACP reductase (AAR) and aldehyde-deformylating oxygenase
      (ADO). AAR catalyzes the reduction of the fatty acyl-ACP/CoA substrates to fatty
      aldehydes, which are then converted into alkanes/alkenes by ADO. These enzymes
      have been widely used for biofuel production by metabolic engineering of
      cyanobacteria and other organisms. However, both proteins, particularly ADO, have
      low enzymatic activities, and their catalytic activities are desired to be
      improved for use in biofuel production. Recently, progress has been made in the
      basic sciences and in the application of AAR and ADO in alkane production. This
      chapter provides an overview of recent advances in the study of the structure and
      function of AAR and ADO, protein engineering of these enzymes for improving
      activity and modifying substrate specificities, and examples of metabolic
      engineering of cyanobacteria and other organisms using AAR and ADO for biofuel
      production.

PMID- 30091095
TI  - Production of Bioplastic Compounds by Genetically Manipulated and Metabolic
      Engineered Cyanobacteria.
AB  - Direct conversion of carbon dioxide to valuable compounds is a desirable way to
      reduce the environmental burden and switch from fossil to renewable fuels.
      Cyanobacteria are photosynthetic bacteria that perform oxygenic photosynthesis
      and are able to produce valuable compounds from carbon dioxide in the air.
      Synechocystis and Synechococcus species, model unicellular cyanobacteria, can
      produce succinate and lactate, which are commodity chemicals used to generate
      bioplastics. Several cyanobacteria are also able to produce polyhydroxybutyrate,
      a biodegradable polyester that accumulates under nitrogen or phosphorus
      starvation. Genetic manipulation succeeded in increasing the productivity of
      succinate, lactate, and polyhydroxybutyrate from cyanobacteria. We summarize the
      recent findings in this review.

PMID- 30091096
TI  - Rewiring of Cyanobacterial Metabolism for Hydrogen Production: Synthetic Biology
      Approaches and Challenges.
AB  - With the demand for renewable energy growing, hydrogen (H2) is becoming an
      attractive energy carrier. Developing H2 production technologies with near-net
      zero carbon emissions is a major challenge for the "H2 economy." Certain
      cyanobacteria inherently possess enzymes, nitrogenases, and bidirectional
      hydrogenases that are capable of H2 evolution using sunlight, making them ideal
      cell factories for photocatalytic conversion of water to H2. With the advances in
      synthetic biology, cyanobacteria are currently being developed as a "plug and
      play" chassis to produce H2. This chapter describes the metabolic pathways
      involved and the theoretical limits to cyanobacterial H2 production and
      summarizes the metabolic engineering technologies pursued.

PMID- 30091097
TI  - Direct Photosynthetic Production of Plastic Building Block Chemicals from CO2.
AB  - Hydroxy acids have attracted attention as building block chemicals due to their
      roles as precursors for the production of various pharmaceuticals, vitamins,
      antibiotics, and flavor compounds as well as monomers for biodegradable plastic
      polyesters. The current approach to hydroxy acid production relies on
      nonrenewable fossil resources such as petroleum for raw materials, raising issues
      such as the rising costs of starting materials and environmental incompatibility.
      Recently, synthetic biology approaches based on the rational design and
      reconstruction of new biological systems were implemented to produce chemicals
      from a variety of renewable substrates. In addition to research using
      heterotrophic organic carbon-dependent Escherichia coli or yeasts, photosynthetic
      microorganisms such as cyanobacteria possessing the ability to absorb solar
      radiation and fix carbon dioxide (CO2) as a sole carbon source have been
      engineered into a new type of microbial cell factory to directly produce hydroxy
      acids from CO2. In this chapter, recent progress regarding the direct
      photosynthetic production of three important hydroxy acids-3-hydroxypropionate (3
      HP), 3-hydroxybutyrate (3-HB), and 3-hydroxyvalerate (3-HV)-from CO2 in
      cyanobacteria is summarized and discussed.

PMID- 30091098
TI  - Engineering Cyanobacteria for Photosynthetic Production of C3 Platform Chemicals
      and Terpenoids from CO2.
AB  - Recent years have witnessed a rising demand for bioproduced chemicals owing to
      restricted availability of petrochemical resources and increasing environmental
      concerns. Extensive efforts have been invested in the metabolic engineering of
      microorganisms for biosynthesis of chemicals and fuels. Among these, direct
      conversion of CO2 to chemicals by photoautotrophic microorganism cyanobacteria
      represents a green route with incredibly potent. Cyanobacteria have been
      engineered for the production of numerous biofuels and chemicals, such as 2,3
      butanediol, fatty acids, isobutyraldehyde, and n-butanol. Under the current
      condition, it might be initially wiser to produce chemicals with higher value or
      higher yield. Photosynthetic production of C3 platform chemicals could withdraw
      carbon close to fixation to maximize the pool of available carbon, thus achieving
      the strong production rates. Photosynthetic production of terpenoids is another
      good choice due to the higher value of these compounds. Here, we review recent
      advances in generating C3 chemicals and valuable terpenoids from cyanobacteria.

PMID- 30091099
TI  - Synthetic Biology Approaches to the Sustainable Production of p-Coumaric Acid and
      Its Derivatives in Cyanobacteria.
AB  - The photosynthetic cyanobacteria are promising candidates for the sustainable
      production of a plethora of plant secondary metabolites, which are beneficial to
      human health but are difficult to produce and purify in other systems. This
      chapter focuses on genetic engineering of Synechocystis PCC 6803 for production
      of p-coumaric acid and its derivatives. Cyanobacterial engineering approaches are
      briefly reviewed. Strategies to increase production yield are discussed,
      including codon optimization of genes expressing enzymatic proteins and a laccase
      coding gene knockout from Synechocystis genome which degrades polyphenols.

PMID- 30091100
TI  - Regulatory Tools for Controlling Gene Expression in Cyanobacteria.
AB  - Cyanobacteria are attractive hosts for converting carbon dioxide and sunlight
      into desirable chemical products. To engineer these organisms and manipulate
      their metabolic pathways, the biotechnology community has developed genetic tools
      to control gene expression. Many native cyanobacterial promoters and related
      sequence elements have been used to regulate genes of interest, and heterologous
      tools that use non-native small molecules to induce gene expression have been
      demonstrated. Overall, IPTG-based induction systems seem to be leaky and
      initially demonstrate small dynamic ranges in cyanobacteria. Consequently, a
      variety of other induction systems have been optimized to enable tighter control
      of gene expression. Tools require significant optimization because they function
      quite differently in cyanobacteria when compared to analogous use in model
      heterotrophs. We hypothesize that these differences are due to fundamental
      differences in physiology between organisms. This review is not intended to
      summarize all known products made in cyanobacteria nor the performance (titer,
      rate, yield) of individual strains, but instead will focus on the genetic tools
      and the inherent aspects of cellular physiology that influence gene expression in
      cyanobacteria.

PMID- 30091101
TI  - Synthetic Gene Regulation in Cyanobacteria.
AB  - Cyanobacteria are appealing hosts for green chemical synthesis due to their use
      of light and carbon dioxide. To optimize product yields and titers, specific and
      tunable regulation of the metabolic pathways is needed. Synthetic biology has
      increased and diversified the genetic tools available for biological process
      control. While early tool development focused on commonly used heterotrophs,
      there has been a recent expansion of tools for cyanobacteria. CRISPR-Cas9 has
      been used to edit the genome of cyanobacterial strains, while transcriptional
      regulation has been accomplished with CRISPR interference and RNA riboswitches.
      Promoter development has produced a significant number of transcriptional
      regulators, including those that respond to chemicals, environmental signals, and
      metabolic states. Trans-acting RNAs have been utilized for posttranscriptional
      and translational control. The regulation of translation initiation is beginning
      to be explored with ribosome binding sites and riboswitches, while protein
      degradation tags have been used to control expression levels. Devices built from
      multiple parts have also been developed to create more complex behaviors. These
      advances in development of synthetic cyanobacterial regulatory parts provide the
      groundwork for creation of new, even more sophisticated bioprocess control
      devices, bolstering the viability of cyanobacteria as sustainable biotechnology
      platforms.

PMID- 30091102
TI  - Identification of Bacterial and Fungal Pathogens in Patients with Post
      Laparoscopic Sleeve Gastrectomy Leakage.
AB  - BACKGROUND: Post-laparoscopic sleeve gastrectomy (LSG) leak leads to serious
      complications, and death may occur. The microbial pattern should be established
      in order to plan empirical antimicrobial therapy. The intra-abdominal leaks post
      LSG were cultured and reviewed. METHODS: Microbial cultures collected from all
      post-sleeve leakage cases managed at the King Khalid University Hospital (KKUH)
      from May 2011 until April 2016 were reviewed. RESULTS: A total of 31 patients
      with positive leak post-LSG were included. The mean presentation time was
      postoperative day 12. Computed tomography (CT) was done for all patients on
      presentation with CT-guided aspiration and drainage next day. Samples from the
      collection were aspirated first for culture then a pigtail drain was kept in
      place. The average time of drain removal was on the 75th postoperative day. A
      total of 28 patients (90.3%) had positive culture results. Candida species were
      the most common organism isolated from 19 patients (61.2%), among them, 10
      (32.2%) were positive for Candida species only. Positive bacterial cultures were
      found in 18 patients (58%). Majority of which single bacterial pathogen isolate,
      only seven patients had two organisms, and four patients had three organisms.
      Klebsiella pneumoniae was the most frequent isolated bacteria [8 patients
      (44.4%)] followed by Streptococcus and Pseudomonas species. Candida albicans was
      the most common Candida species isolated, 13 patients (68.4%). CONCLUSION: Fungal
      microbes isolated from post-LSG leak collection are common and could be
      considered in the primary empirical therapy. The antibiotic choice for the leak
      should cover Klebsiella, Streptococcus, and Pseudomonas until definitive culture
      results are obtained.

PMID- 30091103
TI  - EUS-Guided Drainage of Post-operative Subphrenic Fluid Collection Through Gastric
      Pouch with a Lumen-Apposing Metal Stent in a Patient with Roux-en-Y Gastric
      Bypass.

PMID- 30091104
TI  - Improving the Prediction of Local Drug Distribution Profiles in the Brain with a
      New 2D Mathematical Model.
AB  - The development of drugs that target the brain is very challenging. A
      quantitative understanding is needed of the complex processes that govern the
      concentration-time profile of a drug (pharmacokinetics) within the brain. So far,
      there are no studies on predicting the drug concentration within the brain that
      focus not only on the transport of drugs to the brain through the blood-brain
      barrier (BBB), but also on drug transport and binding within the brain. Here, we
      develop a new model for a 2D square brain tissue unit, consisting of brain
      extracellular fluid (ECF) that is surrounded by the brain capillaries. We
      describe the change in free drug concentration within the brain ECF, by a partial
      differential equation (PDE). To include drug binding, we couple this PDE to two
      ordinary differential equations that describe the concentration-time profile of
      drug bound to specific as well as non-specific binding sites that we assume to be
      evenly distributed over the brain ECF. The model boundary conditions reflect how
      free drug enters and leaves the brain ECF by passing the BBB, located at the
      level of the brain capillaries. We study the influence of parameter values for
      BBB permeability, brain ECF bulk flow, drug diffusion through the brain ECF and
      drug binding kinetics, on the concentration-time profiles of free and bound drug.

PMID- 30091105
TI  - Cutting Deep: The Transformative Power of Art in the Anatomy Lab.
AB  - On Tuesday evenings at New York University School of Medicine (NYUSoM), the
      anatomy lab is transformed into an art studio. Medical students gather with a
      spirit of creative enterprise and a unique goal: to turn anatomy into art. They
      are participants in Art & Anatomy, an innovative drawing course within the Master
      Scholars Program in Humanistic Medicine (MSPHM)-a component of NYUSoM, which
      offers elective courses across a range of interdisciplinary topics in medical
      humanities. Art & Anatomy has had approximately four hundred fifty participants
      since its inception in 2009. The educational intention of the course is to use
      drawing as an active mode of learning that enhances visual-perceptual ability and
      three-dimensional (3D) spatial understanding of the body's interior; however, the
      course also opens a creative space for participants to process the emotional
      complexities of cadaver dissection and the anatomy lab experience. The anatomy
      lab can be the training ground for clinical detachment, but many U.S. medical
      schools are beginning to attend more closely to the emotional aspects of
      dissection. The authors maintain that the inherently expressive nature of drawing
      makes the Art & Anatomy course a novel and effective approach to this endeavor.
      Select student artwork and a curriculum overview are provided.

PMID- 30091106
TI  - Medical Students' Efforts to Integrate and/or Reclaim Authentic Identity:
      Insights from a Mask-Making Exercise.
AB  - Medical students' mask-making can provide valuable insights into personal and
      professional identity formation and wellness. A subset of first- and second-year
      medical students attending a medical school wellness retreat participated in a
      mask-making workshop. Faculty-student teams examined student masks and
      explanatory narratives using visual and textual analysis techniques. A
      quantitative survey assessed student perceptions of the experience. We identified
      an overarching theme: "Reconciliation/reclamation of authentic identity." The
      combination of nonverbal mask-making and narrative offers rich insights into
      medical students' experience and thinking. This activity promoted reflection and
      self-care, while providing insight regarding personal and professional
      development.

PMID- 30091107
TI  - Critical Healing: Queering Diagnosis and Public Health through the Health
      Humanities.
AB  - This introduction provides an overview to a special issue on Critical Healing,
      which draws on queer theory, disability studies, postcolonial theory, and
      literary studies to theorize productive engagements between the clinical and
      cultural aspects of biomedical knowledge and practice. The essays in this issue
      historicize and theorize diagnosis, particularly diagnosis that impacts trans
      health and sexuality, homosexuality, and HIV/AIDS transmission. The essays also
      address racialization, disability, and colonialism through discussions of
      fiction, film, theoretical memoir, and comics, as well as biomedical discourse
      and knowledge.

PMID- 30091108
TI  - Evaluating TNM stage prognostic ability in a population-based cohort of gastric
      adenocarcinoma patients in a low-incidence country.
AB  - OBJECTIVES: TNM stage is the preeminent cancer staging system and a fundamental
      determinant of disease prognosis. Our goal was to evaluate the predictive power
      of TNM stage for gastric adenocarcinoma (GAC), in a low-incidence country.
      METHODS: A province-wide chart review of GAC patients diagnosed from April 1,
      2005 to March 31, 2008 was conducted in Ontario and linked to routinely collected
      vital status data with a follow-up on March 31, 2012. TNM staging was classified
      using the sixth and seventh Union International for Cancer Control/American Joint
      Committee on Cancer editions. Kaplan-Meier and log-rank tests compared stage
      stratified survival estimates. Discrimination was evaluated using Harrell's C
      statistic. RESULTS: The cohort included 2366 patients. One- and 5-year survival
      was 43% and 17%. Using the sixth edition, 9% of patients had stage I disease,
      5.4% stage II, 7.3% stage III, and 64% stage IV; 15% were not staged. Using the
      seventh edition, 9% were stage I, 7.7% stage II, 16% stage III, and 54% stage IV;
      14% were not staged. Stage-stratified 5-year survival ranged from 68% to 7% with
      the sixth edition and from 70% to 4% with the seventh edition. Harrell's C
      statistic was 0.64 (0.63-0.65) for the broad sixth edition staging categories and
      0.68 (0.67-0.69) for the broad seventh edition. Discriminative power was similar
      for the refined stage categories and across multiple subgroup analyses; it was
      best in non-metastatic patients. CONCLUSION: Existing staging systems for GAC
      used in North America predict individualized prognosis poorly. The creation of a
      more complex prediction tool is necessary to provide accurate and precise
      prognostication information to oncologists, patients, and their families.

PMID- 30091110
TI  - Elective cesarean delivery at term and the long-term risk for respiratory
      morbidity of the offspring.
AB  - Maternal morbidity is associated with cesarean deliveries. However, new evidence
      suggests that short- and long-term neonatal morbidity is also associated. This
      includes respiratory morbidity with conflicting results. To determine whether
      mode of delivery has an impact on the long-term risk for respiratory morbidity in
      the offspring, a population-based cohort analysis was conducted including all
      singleton term deliveries occurring between 1991 and 2014 at a single tertiary
      medical center. A comparison was performed between children delivered via
      elective cesarean delivery (CD) and those delivered vaginally. Multiple
      gestations and fetuses with congenital malformations were excluded from the
      analysis as were all cases of urgent CDs. Pediatric hospitalizations involving
      respiratory morbidity of offspring up to the age of 18 years were evaluated. A
      Kaplan-Meier survival curve was used to compare cumulative respiratory morbidity
      incidence and a Cox regression model to control for confounders. During the study
      period, 132,054 term deliveries met the inclusion criteria; 8.9% were via
      elective CDs (n = 11,746) and 91.1% (n = 120,308) were vaginal deliveries.
      Hospitalizations of the offspring involving respiratory morbidity were
      significantly more common in offspring delivered by CDs (5.2 vs. 4.3% in vaginal
      deliveries, p < 0.001). The Kaplan-Meier survival curve demonstrated a
      significantly higher cumulative incidence of respiratory morbidity in the
      elective CD group (log rank p < 0.001). In a Cox proportional hazards model,
      while controlling for maternal age, gestational age, and birthweight, CD
      exhibited a significant and independent association with long-term respiratory
      morbidity of the offspring (adjusted hazard ratio = 1.22 (CI, 1.12-1.33), p <
      0.001).Conclusion: Elective cesarean delivery at term is a significant risk
      factor for long-term pediatric respiratory morbidity of the offspring. What is
      Known: * Cesarean delivery is a major surgery with known possible complications.
      * Cesarean delivery has possible immediate complications for the newborn
      including respiratory complications. What is New: * Our study shows more long
      term respiratory morbidity in the CD group including asthma and obstructive sleep
      apnea. * Different possible explanations have been proposed including exposure to
      maternal flora during vaginal delivery and the stress hormones secreted during
      contractions and delivery.

PMID- 30091112
TI  - A New Optimized Thresholding Method Using Ant Colony Algorithm for MR Brain Image
      Segmentation.
AB  - Image segmentation is considered as one of the most fundamental tasks in image
      processing applications. Segmentation of magnetic resonance (MR) brain images is
      also an important pre-processing step, since many neural disorders are associated
      with brain's volume changes. As a result, brain image segmentation can be
      considered as an essential measure toward automated diagnosis or interpretation
      of regions of interest, which can help surgical planning, analyzing changes of
      brain's volume in different tissue types, and identifying neural disorders. In
      many neural disorders such as Alzheimer and epilepsy, determining the volume of
      different brain tissues (i.e., white matter, gray matter, and cerebrospinal
      fluids) has been proven to be effective in quantifying diseases. A traditional
      way for segmenting brain images involves the use of a medical expert's experience
      in manually determining the boundary of different regions of interest in brain
      images. It may seem that manual segmentation of MR brain images by an expert is
      the first and the best choice. However, this method is proved to be time
      consuming and challenging. Hence, numerous MR brain image segmentation methods
      with different degrees of complexity and accuracy have been introduced recently.
      Our work proposes an optimized thresholding method for segmentation of MR brain
      images using biologically inspired ant colony algorithm. In this proposed
      algorithm, textural features are adopted as heuristic information. Besides, post
      processing image enhancement based on homogeneity is also performed to achieve a
      better performance. The empirical results on axial T1-weighted MR brain images
      have demonstrated competitive accuracy to traditional meta-heuristic methods, K
      means, and expectation maximization.

PMID- 30091109
TI  - Children's complex care needs: a systematic concept analysis of multidisciplinary
      language.
AB  - Complex care in the arena of child health is a growing phenomenon. Although
      considerable research is taking place, there remains limited understanding and
      agreement on the concept of complex care needs (CCNs), with potential for
      ambiguity. We conducted a systematic concept analysis of the attributes,
      antecedents, and consequences of children's CCNs from a multidisciplinary
      perspective. Our data sources included PubMed, Cumulative Index to Nursing and
      Allied Health Literature, and PsycINFO. Inclusion criteria included publications
      in peer-reviewed journals between January 1990 and December 2017, written in the
      English language. One hundred and forty articles were included. We found that
      children's CCNs refer to multidimensional health and social care needs, in the
      presence of a recognized medical condition or where there is no unifying
      diagnosis.Conclusion: Children's CCNs are individual and contextualized, are
      continuing and dynamic, and are present across a range of settings, impacted by
      family and healthcare structures. There remain extensive challenges to caring for
      these children and their families, precluding the possibility that any one
      profession can possess the requisite knowledge or scope to singularly provide
      high-quality competent care. What is Known: * Complex care is a growing
      phenomenon and population prevalence figures show that there is an increasing
      number of children with complex care needs (CCNs). However, the concept has not
      been systematically analyzed before, leaving it generally ill-defined and at
      times confusing. What is New: * This is the first time this concept has been
      systematically analyzed and this analysis provides a much-needed theoretical
      framework for understanding the multidimensional nature of CCNs in children. *
      Children's CCNs refer to multidimensional health and social care needs in the
      presence of a recognized medical condition or where there is no unifying
      diagnosis. They are individual and contextualized, are continuing and dynamic,
      and are present across a range of settings, impacted by family and healthcare
      structures. It is clear that the very nature of CCNs precludes the possibility
      that any one profession or discipline can possess the requisite knowledge or
      scope for high-quality competent care for this population.

PMID- 30091111
TI  - Evolution of body mass index in children with type 1 diabetes mellitus.
AB  - The prevalence of childhood overweight and obesity has risen during the last 30
      years, not only in children with type 2 diabetes, but also those with type 1
      (T1D) and this is linked with an increased cardiovascular risk. A better
      understanding of weight patterns in the years after diagnosis of T1D is important
      to identify those children with a risk for excess weight gain and strategies to
      decrease this. We retrospectively analyzed data of all children with T1D followed
      at the department of Pediatric Endocrinology Leuven and diagnosed between 1991
      and 2015. Data as age, sex, BMI, and Tanner score were extracted in 390 subjects.
      Standardized BMI (BMI SDS) in this study group using all data was 0.26. An
      increase in BMI SDS was seen as a function of time since diagnosis and age, both
      being independent predictors. Data comparison showed a significant stronger
      relation between BMI SDS and both time since diagnosis and age in girls. Children
      diagnosed after puberty showed a higher increase in BMI SDS.Conclusion: These
      longitudinal data suggest an important increase in BMI in children with T1D, both
      as a function of time since diagnosis and age, especially in girls. What is
      Known: * The prevalence of childhood overweight and obesity is risen during the
      last 30 years, in children with type 2 diabetes, but also those with type 1
      diabetes. What is New: * Our study demonstrates with longitudinal data an
      increase in BMI in children with type 1 diabetes, especially girls. The increase
      in BMI SDS is seen as a function of time since diagnosis and age, both being
      independent predictors. Given the increased risk of metabolic syndrome and other
      complications in overweight children, special attention is needed to prevent this
      evolution.

PMID- 30091113
TI  - In-hospital cardiovascular events after liver transplantation: predictors and
      long-term outcome.
AB  - INTRODUCTION: Liver transplantation has emerged as a successful therapy for end
      stage liver disease. However, cardiovascular mortality is the leading cause of
      fatality in the postoperative period. The aim of this study was to reveal the
      prevalence and identify risk factors of early cardiovascular events (CVEs).
      METHODS: We performed a retrospective study of all consecutive patients who
      underwent a primary liver transplantation from 1986 to 2017 (n = 916). We
      investigated the occurrence of in-hospital CVEs, their predictors, and short- and
      long-term outcome. RESULTS: The prevalence of CVEs was 11%. The adjusted analysis
      showed that higher age (OR 1.06, 95% CI 1.03-1.09), higher MELD score (OR 1.04,
      95% CI 1.01-1.07 CI) and sinus tachycardia at time of screening (OR 3.12, 95% CI
      1.45-6.72) were positive predictors for a CVE. Preoperative propranolol use
      showed a trend towards a higher risk of CVE (OR 1.66, 95% CI 1.00-2.77, p =
      0.051). In a sub-analysis of patients where echocardiography data were available
      (n = 597), a larger left atrial diameter and a higher E/E' ratio were related to
      early CVEs. Ten-year survival in 30-day survivors was favourable (68.6%; 56.0%
      vs. 69.8% in the CVE+ vs. the CVE-group, respectively, p = 0.056). DISCUSSION: In
      conclusion, besides known risk factors (age and MELD score), sinus tachycardia
      (related to the presence of acute liver failure and cirrhosis) was an independent
      predictor for CVE after liver transplantation.

PMID- 30091114
TI  - Luis Schut, MD, FAANS(L). 1932-2018.

PMID- 30091115
TI  - Infantile stroke: consider minor head trauma.

PMID- 30091116
TI  - Menophila: a poetic description of genital ambiguity in Hellenistic literature.

PMID- 30091117
TI  - An insight into familial hypercholesterolemia in Greece: rationale and design of
      the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH).
AB  - Familial hypercholesterolemia (FH) is the most common metabolic genetic disorder.
      It is estimated that around 13 million people worldwide have FH. At the same
      time, only 25% of FH patients have been diagnosed. Moreover, these patients are
      often undertreated. The true prevalence of FH in Greece is unknown, but it is
      estimated that there are at least 40,000 FH patients nationwide pointing to a
      prevalence of 1:250. Patients with FH are at a high risk for cardiovascular
      events and death at an early age. Therefore, prompt detection of these patients
      is of pivotal importance in order to implement appropriate preventive measures at
      a young age. Patient registries are a powerful tool for recording and monitoring
      a disease and promoting clinical practices, thus contributing to improved
      outcomes and reduction of healthcare costs. National registries of FH patients
      have been a success in the Netherlands, Spain and Wales. As Greece did not have a
      national FH registry, the Hellenic Atherosclerosis Society has organized,
      established and funded the Hellenic Familial Hypercholesterolemia (HELLAS-FH)
      national registry in order to promote a better understanding of FH in our
      country.

PMID- 30091118
TI  - Ketogenic diet and testosterone increase: Is the increased cholesterol intake
      responsible? To what extent and under what circumstances can there be benefits?

PMID- 30091120
TI  - Addressing the Lack of Competition in Generic Drugs to Improve Healthcare Quality
      and Safety.
AB  - A lack of access to critical drugs in the USA, either due to exorbitant prices or
      shortages, has become a troubling norm that threatens the quality and safety of
      healthcare. In 2017, there were shortages of 146 commonly used drugs including
      electrolytes, chemotherapy, cardiovascular, and antibiotic agents. For example,
      there currently exists a shortage in intravenous fluids and injectable opioids
      (both in chronic short supply for years) that has been respectively ascribed to
      disruptions in pharmaceutical manufacturing by Hurricane Maria and manufacturing
      delays. These explanations, however, mask a more fundamental and avoidable cause:
      a lack of healthy competition in the generic drug market which is likely
      contributing to price hikes and shortages. By understanding this underlying
      cause, we hope to illuminate a pathway from our current state of complacency,
      where drug price hikes and shortages are routine, to a future state of effective
      action, where patients have reliable access to vital drugs. This article outlines
      a roadmap to influence incentives, regulations, new drug development, and
      ultimately stakeholder (i.e., patients, providers, and drug makers) behavior to
      enhance competition, with the ultimate aim of improving the quality and safety of
      healthcare for our patients.

PMID- 30091119
TI  - Clinical-grade mesenchymal stem cells derived from umbilical cord improve septic
      shock in pigs.
AB  - BACKGROUND: Septic shock is the leading cause of death in intensive care units.
      The pathophysiological complexity of this syndrome contributes to an absence of
      specific treatment. Several preclinical studies in murine models of septic shock
      have shown improvements to organ injury and survival after administration of
      mesenchymal stem cells (MSCs). To better mimic a clinical approach in humans, we
      investigated the impact of randomized controlled double-blind administration of
      clinical-grade umbilical cord-derived MSCs to a relevant pig model of septic
      shock. METHODS: Septic shock was induced by fecal peritonitis in 12 male domestic
      pigs. Animals were resuscitated by an experienced intensivist including fluid
      administration and vasopressors. Four hours after the induction of peritonitis,
      pigs were randomized to receive intravenous injection of thawed umbilical cord
      derived MSCs (UCMSC) (1 * 106 UCMSCs/kg diluted in 75 mL hydroxyethyl starch
      (HES), (n = 6) or placebo (HES alone, n = 6). Researchers were double-blinded to
      the treatment administered. Hemodynamic parameters were continuously recorded.
      Gas exchange, acid-base status, organ function, and plasma cytokine
      concentrations were assessed at regular intervals until 24 h after the onset of
      peritonitis when animals were sacrificed under anesthesia. RESULTS: Peritonitis
      induced profound hypotension, hyperlactatemia, and multiple organ failure. These
      disorders were significantly attenuated when animals were treated with UCMSCs. In
      particular, cardiovascular failure was attenuated, as attested by a better mean
      arterial pressure and reduced lactatemia, despite lower norepinephrine
      requirements. As such, UCMSCs improved survival in this very severe model (60%
      survival vs. 0% at 24 h). CONCLUSION: UCMSCs administration is beneficial in this
      pig model of polymicrobial septic shock.

PMID- 30091122
TI  - Important Steps Towards a Clinically Actionable Predictive Model of Opioid
      Overdose Among Patients on Long-term Opioid Therapy.

PMID- 30091121
TI  - Randomized Trial of Personalized Breast Density and Breast Cancer Risk
      Notification.
AB  - BACKGROUND: Despite widespread implementation of mammographic breast density
      (MBD) notification laws, the impact of these laws on knowledge of MBD and
      knowledge of breast cancer risk is limited by the lack of tools to promote
      informed decision-making in practice. OBJECTIVE: To develop and evaluate whether
      brief, personalized informational videos following a normal mammogram in addition
      to a legislatively required letter about MBD result can improve knowledge of MBD
      and breast cancer risk compared to standard care (i.e., legislatively required
      letter about MBD included with the mammogram result). DESIGN/PARTICIPANTS:
      Prospective randomized controlled trial of English-speaking women, age 40-74
      years, without prior history of breast cancer, receiving a screening mammogram
      with a normal or benign finding (intervention group n = 235, control group n =
      224). INTERVENTION: brief (3-5 min) video, personalized to a woman's MBD result
      and breast cancer risk. MAIN MEASURES: Primary outcomes were a woman's knowledge
      of her MBD and risk of breast cancer. Secondary outcomes included whether a woman
      reported that she discussed the results of her mammogram with her primary care
      provider (PCP). KEY RESULTS: Relative to women in the control arm, women in the
      intervention arm had greater improvement in their knowledge of both their
      personal MBD (intervention pre/post 39.2%/ 77.5%; control pre/post 36.2%/ 37.5%;
      odds ratio (OR) 5.34 for change for intervention vs. control, 95% confidence
      interval (CI) 3.87-7.36; p < 0.001) and risk of breast cancer (intervention
      pre/post: 66.8%/74.0%; control pre/post 67.9%/ 65.2%; OR 1.42, 95% confidence
      interval (CI) 1.09-1.84; p = 0.01). Women in the intervention group were more
      likely than those in the control group to report discussing the results of their
      mammogram with their PCP (p = 0.05). CONCLUSIONS: Brief, personalized videos
      following mammography can improve knowledge of MBD and personal risk of breast
      cancer compared to a legislatively mandated informational letter. Trial
      Registration Clinicaltrials.gov (NCT02986360).

PMID- 30091123
TI  - Racial Discrimination in Health Care and Utilization of Health Care: a Cross
      sectional Study of California Adults.
AB  - BACKGROUND: Racial and ethnic discrimination in health care have been associated
      with suboptimal use of health care. However, limited research has examined how
      facets of health care utilization influence, and are influenced by,
      discrimination. OBJECTIVE: This study aimed to determine if type of insurance
      coverage and location of usual source of care used were associated with
      perceptions of racial or ethnic discrimination in health care. Additionally, this
      study examined if perceived racial or ethnic discrimination influenced delaying
      or forgoing prescriptions or medical care. DESIGN: Data from the 2015-2016
      California Health Interview Survey were used. Logistic regression models
      estimated odds of perceiving racial or ethnic discrimination from insurance type
      and location of usual source of care. Logistic regression models estimated odds
      of delaying or forgoing medical care or prescriptions. PARTICIPANTS: Responses
      for 39,171 adults aged 18 and over were used. MAIN MEASURES: Key health care
      utilization variables were as follows: current insurance coverage, location of
      usual source of care, delaying or forgoing medical care, and delaying or forgoing
      prescriptions. We examined if these effects differed by race. Ever experiencing
      racial or ethnic discrimination in the health care setting functioned as a
      dependent and independent variable in analyses. KEY RESULTS: When insurance type
      and location of care were included in the same model, only the former was
      associated with perceived discrimination. Specifically, those with Medicaid had
      66% higher odds of perceiving discrimination, relative to those with employer
      sponsored coverage (AOR = 1.66; 95% CI 1.11, 2.47). Race did not moderate the
      impact of discrimination. Perceived discrimination was associated with higher
      odds of delaying or forgoing both prescriptions (AOR = 1.97; 95% CI 1.26, 3.09)
      and medical care (AOR = 1.84; 95% CI 1.31, 2.59). CONCLUSIONS: Health care
      providers have an opportunity to improve the experiences of their patients,
      particularly those with publicly sponsored coverage.

PMID- 30091125
TI  - Clinical applications of a computed tomography color "marrow mapping" algorithm
      to increase conspicuity of nondisplaced trabecular fractures.
AB  - PURPOSE: To explore clinical applications of a novel conventional computed
      tomography (CT) color post-processing algorithm to increase conspicuity of
      nondisplaced trabecular fractures. MATERIALS AND METHODS: The algorithm was
      created in Adobe Photoshop and Adobe Extendscript, utilizing DICOM images from
      conventional CT as source images. A total of six representative cases were
      selected and processed. No statistical analyses were performed. RESULTS: A total
      of six cases are demonstrated, five with MRI correlation demonstrating
      corresponding fractures and bone marrow edema, including a case of sacral
      insufficiency fracture, two cases of vertebral body fracture, two cases of
      nondisplaced hip fracture, and a knee bone marrow edema lesion (without MRI
      correlate). All cases were processed successfully without error. CONCLUSIONS: A
      conventional CT color post-processing algorithm may be clinically useful in
      increasing conspicuity of nondisplaced fractures and bone marrow edema. A
      potential pitfall is the presence of subchondral or marrow sclerosis, which may
      mimic edema. Future prospective studies will be necessary to evaluate diagnostic
      performance.

PMID- 30091124
TI  - Tumour origin and R1 rates in pancreatic resections: towards consilience in
      pathology reporting.
AB  - To evaluate differences in the R1 rates of ampullary (AC), pancreatic (PC), and
      distal bile duct (DBD) cancers in pancreatoduodenectomies (PD) using standardised
      pathology assessment. Data of PD (2010-2011) analysed in accordance with the
      Royal College of Pathologists (UK) protocol, were retrieved. Clinicopathologic
      features, including frequency, topography, and mode of margin involvement in AC
      (n = 87), PC (n = 18), and DBD (n = 5) cancers were evaluated. The R1 rate was
      7%, 67%, and 20% in the AC, PC, and DBD cancers (p < 0.001). Within the PC
      cohort, R1 rate was heterogeneous (chemo-naive, 77%; post-neoadjuvant, 40%).
      Commonest involved margins were as follows: posterior in overall PD (35%), AC
      (43%), overall PC (33%), and post-neoadjuvant PC (100%); superior mesenteric
      artery margin in chemo-naive PC (38%) and common bile duct margin in DBD (100%)
      cancers. In AC, majority (66%) of R1 were signet ring cell type. Indirect margin
      involvement due to tumour within lymph node, perineural sheath or lymphovascular
      space was observed in 26% cases, and altered R1 rate in AC, PC, and DBD cohorts
      by 1%, 12%, and 0%, respectively. Although not statistically significant,
      patients with R1 had lower disease-free survival than those with R0 (mean, 25.4
      months versus 44.4 months). Tumour origin impacts R1 data in PD necessitating its
      accurate classification by pathologists. Indirect involvement, histology, and
      neoadjuvant therapy influence the R1 rate, albeit in a minority of cases.
      Generating cogent R1 data based on standardised pathology reporting is the
      foremost need of the hour.

PMID- 30091126
TI  - Association of type 2 diabetes susceptible genes GCKR, SLC30A8, and FTO
      polymorphisms with gestational diabetes mellitus risk: a meta-analysis.
AB  - PURPOSE: Current studies have detected the correlation of polymorphisms in type 2
      diabetes susceptible genes GCKR, SLC30A8 and FTO with gestational diabetes
      mellitus (GDM) risk. However, findings of these studies were incongruous. Hence,
      we performed an integrated review and meta-analysis for the researches regarding
      the association of single nucleotide polymorphisms (SNPs) in GCKR, SLC30A8 and
      FTO genes and GDM risk. METHODS: Eligible publications were selected on the basis
      of several inclusion and exclusion criteria. Correlation between each SNP and GDM
      risk was estimated by computing odds ratios (ORs) with 95% confidence intervals
      (95%CIs). RESULTS: Consequently, 19 case-control studies (from 16 citations)
      including 3636 GDM cases and 7229 GDM-free controls were participated in a meta
      analysis of seven prevalent SNPs (GCKR rs1260326 and rs780094; SLC30A8 rs13266634
      and rs11558471; FTO rs8050136, rs1421085 and rs9939609). Our results demonstrated
      that the rs780094, rs13266634 and rs9939609 SNPs were significantly associated
      with GDM risk. In stratified analysis, correlations of rs780094 and rs13266634
      SNPs could be observed in Asian and Caucasian subgroups. Moreover, association
      between rs9939609 SNP and GDM risk was detected in Caucasian subgroup.
      CONCLUSIONS: The GCKR rs780094, SLC30A8 rs13266634 and FTO rs9939609 SNPs were
      demonstrated to be the potential biomarkers for GDM risk prediction.

PMID- 30091127
TI  - Incidental focal thyroid uptake on 18F-Choline PET-CT: need to rule out thyroid
      cancer.

PMID- 30091128
TI  - Mean Platelet Volume and Testicular Torsion: New Findings.
AB  - INTRODUCTION: Testicular torsion is an emergency at any age; the aim of this
      study is to evaluate the role of mean platelet volume to assess the viability of
      the testes before surgeryMaterials and methods: We retrospectively analysed the
      medical records of consecutive patients who underwent surgical exploration for
      acute scrotal pathology between January 2014 and December 2016 in our
      institution.Patients were divided into two groups (detorsion of testes and
      orchyectomy); a third group was created as control group. All patients underwent
      blood exam before surgery; inclusion and exclusion criteria were created. We also
      evaluated the association between mean platelets volume and the testicular
      recovery during surgeryResult: After reviewing medical charts following the
      inclusion and exclusion criteria, 8 patients were enrolled in Group 1 and 11
      patients in Group 2. 33 healthy controls were enrolled in Group 3. MPV value in
      Group 1 resulted significantly different (p < 0.01) from the value in Group 2 and
      3. The duration of symptoms was shorter than 6 hours in 4/8 (50%) patients in
      Group 1; this early referral to hospital allowed prompt detorsion and testicular
      recovery. In these "early-presenting" patients, MPV value was significantly lower
      than in patients with torsion of testicular appendage (p = 0.01) and in controls
      (p = 0.001). CONCLUSION: MPV could be a useful adjunct in diagnosing TT, aiding
      its differential diagnosis with Torsion of the testicular appendage. The lower
      MPV value in "early-presenting" patients with TT suggests a role in predicting
      the testis viability, and therefore the appropriate treatment.

PMID- 30091129
TI  - The correlation between serum LDL-cholesterol and arterial wall stiffness.
AB  - BACKGROUND: Elevated serum LDL-cholesterol is a risk factor of atherosclerosis,
      which involves remodeling of the arterial walls with their subsequent stiffening.
      AIM: The aim of the study was to evaluate the relationships between serum lipids
      and arterial wall elastic properties. METHODS: The study group comprised 315 men
      and women aged 55.84+/-9.44 years. Serum glucose and lipid concentrations were
      estimated. All subjects underwent blood pressure measurement, transthoracic
      echocardiography and assessment of vascular compliance of large (C1) and small
      arteries (C2) using an HDI/Pulse WaveTM CR-2000 Research Cardiovascular Profiling
      Instrument. The subjects were divided into three groups: group I - LDL
      cholesterol <2.6mmol/L, group II - LDL-cholesterol >=2.6 mmol/L and <4.0 mmol/L,
      and group III - LDL-cholesterol >=4.0 mmol/L. RESULTS: There were no differences
      between the groups with regard to smoking status (p =0.56), serum glucose (p
      =0.13), BMI (p =0.96), systolic (p =0.17) and diastolic blood pressure (p =0.29),
      or C1 (p =0.09). On the other hand, C2 was higher in group I and II than in group
      III (5.12+/-2.57 vs. 5.18+/-2.75 vs. 4.20 +/- 1.58 ml/mmHg*100, respectively, p <
      0.01). The multivariate regression analysis negated independent associations
      between C1 and serum lipids. In contrast, C2 was associated independently
      inversely with serum LDL-cholesterol concentration (r = -0.18, p < 0.01).
      CONCLUSIONS: Higher serum LDL-cholesterol concentration seems to contribute
      independently to stiffening of small arterial vasculature in otherwise healthy
      adults. Screening for dyslipidaemia in the general population and its prompt
      treatment are most desirable.

PMID- 30091130
TI  - Longevity and cardiovascular mortality of Polish elite football players.
AB  - BACKGROUND: Despite the wide popularity of football, there is a paucity of
      scientific evidence explaining the relationship between being a competitive
      footballer and life expectancy AIM: The study analyses and compares cause
      specific mortality between Polish elite footballers (men) and the general male
      population. METHODS: A retrospective method of analysis is employed to study a
      sample of 455 elite footballers who died between 1990 and 2015. The cause of
      death was established based on the official statistics of Polish Central
      Statistical Office. The comparative sample consists of men in the general male
      population in Poland who died in the sampled period being at least 25 years of
      age at the time of death. RESULTS: The mean age at death turned out to be higher
      for footballers than controls (70.2 vs 67.4 years). Cardiovascular diseases were
      a more common cause of death among footballers than in the general male
      population in both the under 65-group and the above- 65-group (46.9% to 32.3% and
      61.3% to 53.3%, respectively). A closer analysis of cause-specific cardiovascular
      mortality revealed that acute myocardial infarction caused more deaths (OR=1.31;
      CI 95%: [1.02-1.68]) and hypertensive disease less deaths (OR=0.20; CI 95%: [0.05
      0.79]) among athletes than in the general male population. CONCLUSIONS: The study
      results point to excess cardiovascular mortality among Polish elite footballers.
      A trend analysis has shown, however, that its level is falling.

PMID- 30091131
TI  - The "double dunk" technique for a right ventricle to pulmonary artery conduit for
      the Norwood procedure reduces the unintended shunt-related events.
AB  - BACKGROUND: The introduction of the right ventricle to pulmonary artery conduit
      (RVPAc) during the Norwood procedure (NP) for hypoplastic left heart syndrome
      (HLHS) resulted in a higher survival rate, but also in an increased number of
      unintended pulmonary and shunt interventions. AIM: We analyse how several
      modifications employed in RVPAc for NP may influence the interstage course,
      surgical or catheter-based unintended interventions and pulmonary arteries
      development in HLHS cohort of patients. METHODS: We performed a retrospective
      analysis of three groups of non-selected, consecutive neonates who underwent the
      NP between 2011 and 2014, with different RVPAc surgical techniques employed:
      Group I - the left RVPAc with distal homograft cuff [ N=32 ], Group II - the
      right RVPAc with distal homograft cuff [ N=28 ], Group III - the "double dunk"
      right reinforced RVPAc [ N=41 ]. RESULTS: There was no difference in terms of
      age, weight, prevalence of aortic atresia, diameter of the ascending aorta, deep
      hypothermic circulatory arrest time and hospital mortality rate ( 9.3 vs. 14.2
      vs. 7.3%, respectively ) between the groups. There was a significant reduction in
      the numbers of catheter-based interventions during the interstage period in the
      third group (34 vs. 25vs. 0 %, respectively, p<0.05) and/or concomitant surgical
      interventions (17.2 vs. 4.1 vs. 2.6%, respectively). The diameter of the
      pulmonary arteries was the most homogenous in the third group. CONCLUSIONS: The
      modified strategy of using the "double dunk", right reinforced RVPAc during the
      NP for HLHS significantly reduces the number of catheter-based and surgical
      unintended shunt-related reinterventions during the interstage period. This
      strategy allows for a more homogenous development of pulmonary arteries before
      the second, surgical stage.

PMID- 30091132
TI  - Cardiac resynchronisation therapy: current benefits and pitfalls.
AB  - Cardiac resynchronisation therapy (CRT) has been shown to reduce all-cause
      mortality, heart failure events, and symptoms while improving exercise capacity
      and quality of life. Nevertheless, despite a large number of multicentre
      randomised trials and clear evidence confirming the above, there is still a
      higher number of patients who fail to develop reverse remodelling. In order to
      select the optimal patient population, the current European Society of Cardiology
      guidelines recommend a simultaneous evaluation of QRS morphology and width.
      However, based on recent data, QRS width itself is a less accurate parameter in
      the prediction of the outcome, as compared to QRS morphology. Furthermore, the
      baseline left ventricular (LV) ejection fraction (LVEF), which is also an known
      criterion for selecting CRT candidates (partly applied due to cost-benefit
      reasons), can be misleading. Data showed that patients with LVEF > 35% might also
      benefit from this type of treatment. Thus, LVEF should be evaluated less
      rigorously when screening patients for resynchronisation therapy. While the
      subsequent beneficial response to CRT is multifactorial, procedure-related
      parameters, such as LV lead position, are also crucial. The first data released
      recently confirmed the previous empiric clinical experience indicating that the
      LV lead should be implanted into the lateral or posterior coronary sinus side
      branch. This location was associated with a better long-term clinical outcome in
      terms of death and heart failure events. Some issues related to CRT are awaiting
      further clarification, such as the choice of the type of the implanted device
      (pacemaker or defibrillator) or the decision about CRT device upgrade. This
      review discusses the current evidence regarding the above, focusing on the
      questions that should be handled with caution or require clarification.

PMID- 30091133
TI  - Acetylsalicylic acid and clopidogrel hyporesponsiveness following acute coronary
      syndromes.
AB  - This review discusses the response variability to acetylsalicylic acid (ASA) and
      particularly to clopidogrel, and their relation to adverse recurrent ischaemic
      events in patients with arterial diseases. The higher rate of ASA resistance
      reported in the literature may be mainly due to the cyclooxygenase-1 non-specific
      assays, non-compliance, and underdosing. Clopidogrel response variability and non
      responsiveness are established concepts. Moreover, high platelet reactivity (HPR)
      to adenosine diphosphate during clopidogrel therapy is now a known risk factor
      for recurrent ischaemic events in high-risk percutaneous coronary
      intervention/acute coronary syndrome patients. Variable active metabolite
      generation is the primary explanation for clopidogrel response variability and
      non-responsivenes. Variable levels of active metabolite generation following
      clopidogrel administration could be mainly explained by functional variability in
      hepatic cytochrome (CYP)P450 isoenzyme activity that is influenced by drug-drug
      interactions and single nucleotide polymorphisms of specific genes encoding
      CYP450 isoenzymes. Treatment with more potent P2Y12 receptor blockers, such as
      prasugrel and ticagrelor are credible alternative strategies to overcome HPR
      during clopidogrel therapy.

PMID- 30091134
TI  - Sex-specific differences in cardiac maladaptation to hypertension and arterial
      stiffening.
AB  - The overall prevalence of symptomatic heart failure (HF) is similar in men and
      women and constitutes about a quarter of the first manifestation of
      cardiovascular disease in both sexes. However, there is an important difference
      between the sexes in the type of HF. Whereas men more frequently develop HF with
      reduced ejection fraction, HF with preserved ejection fraction is especially
      frequent in women. The major risk factors for symptomatic HF are high blood
      pressure and arterial stiffness, which evoke a complex network of functional and
      structural changes in the heart in both men and women. In this review, we will
      discuss the recent epidemiological data on sex discrepancies in cardiac
      maladaptation to hypertension and arterial stiffening.

PMID- 30091135
TI  - Education, cardiovascular risk factors and blood pressure control in hypertensive
      outpatients.
AB  - BACKGROUND: The lack of knowledge of hypertension and other cardiovascular risk
      factors continues to be a major challenge for blood pressure (BP) control and
      effective prevention of cardiovascular disease. AIM: This prospective, single
      centre, open-label, randomised study was designed to evaluate the impact of
      education on cardiovascular risk control and target BP values in hypertensive
      outpatients. METHODS: We studied 201 consecutive hypertensive outpatients during
      the first outpatient visit. Of them, 101 subjects were included in the active
      education group (Group E1) and were offered extra workshops additional to the
      standard visits. The next 100 patients (control group) received standard
      information and medical service during each ambulatory visit (Group E0). The
      follow-up period was 12 months. In both groups, cardiometabolic comorbidities,
      global cardiovascular risk, and the range of BP control were analysed. RESULTS:
      We observed significant systolic BP (SBP) reduction during the follow-up period
      in the studied population, as assessed by three different BP control methods:
      home BP measurement (HBPM; -4.0 mmHg; p < 0.001), office BP measurement (OBPM; 
      9.6 mmHg; p < 0.001), and ambulatory BP monitoring (ABPM; -4.8 mmHg; p < 0.001).
      Similar results were noted in terms of diastolic BP (DBP) reduction in OBPM (
      11.3 mmHg; p = 0.001) and ABPM (-2.7 mmHg; p = 0.001). We found no correlation
      between education intensity and the achieved BP reduction. We observed a decrease
      in the percentage of obese patients in Group E1 (84.3% vs. 76.0%; p < 0.001).
      CONCLUSIONS: A significant BP.

PMID- 30091136
TI  - Outcomes in patients undergoing cardiac resynchronisation therapy complicated by
      device-related infective endocarditis.
AB  - BACKGROUND: Cardiac device-related infective endocarditis (CDRIE) is one of the
      most serious complications of cardiac resynchronisation therapy (CRT). AIM: We
      sought to assess clinical outcomes and their determinants in CRT patients with
      CDRIE. METHODS: A tertiary cardiology centre database was screened to identify
      all CDRIE cases, diagnosed based on the modified Duke criteria, amongst 765
      consecutive CRT implantations performed between 2002 and 2015 (70.8% de novo
      implantations, 29.2% upgrades). RESULTS: During the median follow-up of 1692 days
      (range: 457-3067 days) CDRIE was diagnosed in 41 (5.4%) patients. Overall, in
      hospital and long-term mortality rates of CDRIE patients were 51.2% and 75.6%,
      respectively. Among patients with CDRIE, in whom the device was vs. was not
      explanted, in-hospital death rates were 39.3% (11/28 patients) vs. 76.9% (10/13
      patients; p = 0.025). In multivariate regression analysis, device removal was
      independently associated with significantly lower in-hospital mortality (hazard
      ratio [HR] 0.09, 95% confidence interval [CI] 0.03-0.35, p = 0.0004). The need
      for temporary pacing after device removal (HR 5.92, 95% CI 1.13-30.96, p =
      0.035), a time period of less than seven days between CDRIE diagnosis and CRT
      removal (HR 6.69, 95% CI 1.48-30.27, p = 0.01), and the highest serum creatinine
      level during infection (HR 1.02, 95% CI 1.004-1.03, p = 0.01) were identified as
      independent predictors of higher in-hospital mortality. CONCLUSIONS: Device
      removal is independently associated with lower mortality in patients with CRT and
      CDRIE. Early device removal (less than seven days since the diagnosis), the need
      for temporary pacing after removal and acute renal failure are independent
      mortality predictors in CRT patients who developed CDRIE.

PMID- 30091137
TI  - Factors determining the choice between subcutaneous or transvenous implantable
      cardioverter-defibrillators in Poland in comparison with other European
      countries: a sub-study of the European Heart Rhythm Association prospective
      survey.
AB  - BACKGROUND: Subcutaneous implantable cardioverter-defibrillator (S-ICD) may be an
      alternative to transvenous ICD (TV-ICD). AIM: We sought to evaluate factors
      determining the choice of S-ICD vs. TV-ICD in Polish patients in comparison to
      other European countries. METHODS: All consecutive patients who underwent TV-ICD
      or S-ICD implantation in centres participating in the European Heart Rhythm
      Association prospective snapshot survey were included. RESULTS: During an eight
      week study period, 429 patients were recruited, including 136 (31.7%) ICD
      patients from Poland (eight with S-ICD). In comparison to other European centres,
      the proportion of S-ICD implantations in Poland was lower (7% vs. 26%, p <
      0.001), whereas the ratio of cardiac resynchronisation therapy defibrillator
      implantations was higher (43% vs. 26%; p < 0.001). Subjects receiving S-ICD in
      Poland were more often over 75 years old (25% vs. 0%, p < 0.001), in New York
      Heart Association class II (87.5% vs. 29.4%, p = 0.001), with chronic kidney
      disease (37.5% vs. 5.9%, p = 0.003), and with lower left ventricular ejection
      fraction (32% [14%-50%] vs. 50% [25%-60%], p = 0.04), compared to other European
      countries. Additionally, in comparison to subjects from other European centres,
      Polish patients were significantly more often implanted with S-ICD due to prior
      infection (37.5% vs. 1.5%, p < 0.001) and a lack of venous access (25% vs. 0%, p
      < 0.001), whereas the largest subset of patients in other European countries were
      implanted with S-ICD because of young age (50% vs. 25%, p = NS). CONCLUSIONS: The
      main reasons leading to S-ICD implantations in Polish patients differ from the
      indications adopted in other European countries. In Poland, patients referred for
      TV-ICD or S-ICD implantation had more advanced heart failure and more
      comorbidities in comparison to subjects from other European countries. S-ICD is
      still underused in Polish patients.

PMID- 30091138
TI  - Sex differences in fetal heart rate and variability assessed by antenatal
      computerized cardiotocography.
AB  - INTRODUCTION: The aim of the current study is to explore the effect of fetal sex
      on the fetal heart rate and variability. MATERIAL AND METHODS: This is a
      retrospective cross-sectional study. We analyzed fetal heart rate (FHR) traces of
      pregnant women that were recorded antenatally using a commercially available
      computerized cardiotocograph (cCTG; Oxford system). Fetal sex was ascertained
      after birth. Baseline FHR and short-term heart rate variation (STV) were compared
      between male and female fetuses. Expected mean values for baseline FHR and STV
      were computed and multiples of the mean (MOMean) of males and females were
      compared. RESULTS: Information on 9259 cases is reported in this study. Baseline
      FHR of female fetuses was significantly higher (P < 0.001) and STV lower (P <
      0.001) than that of male fetuses. This difference remained even after the effects
      of gestational age and diurnal variation were eliminated by computation of
      MOMean, but the absolute differences in the baseline FHR (0.9 beats/min [bpm])
      and STV (0.246 ms) between male and female fetuses were small. A significant
      negative correlation was found between baseline FHR and STV (r = -0.518, P <
      0.001). Similarly, a significant negative correlation was found between the
      MoMean of baseline FHR and MoMean STV (r = -0.481, P < 0.001). CONCLUSIONS: Using
      the Oxford cCTG, male fetuses show a significantly lower baseline FHR and greater
      variability as compared with female fetuses. However, the absolute differences
      are small and may not be of major clinical significance.

PMID- 30091139
TI  - Preoperative Anemia, Functional Outcomes, and Quality of Life After Hip Fracture
      Surgery.
AB  - OBJECTIVES: To determine whether preoperative anemia, perioperative blood
      transfusion, and predischarge anemia affect function and health-related quality
      of life (HRQoL) after hip fracture surgery. DESIGN: Retrospective single-center
      cohort study PARTICIPANTS: Individuals undergoing traumatic hip fracture surgery
      from 2012 to 2016 (N=973). MEASUREMENTS: Demographic data, Charlson Comorbidity
      Index, preoperative hemoglobin level, perioperative blood transfusion,
      predischarge hemoglobin level, type of surgery (replacement or fixation). Anemia
      was divided into quintiles at 10.0, 11.0, 12.0, and 13.0 g/dL. Baseline, 6-week,
      and 6-month Harris Hip Scale (HHS), Parker Mobility Scale (PMS), and Medical
      Outcomes Study 36-item Short-Form Health Survey (SF-36) scores were obtained.
      PMS; HHS and SF-36 role physical (RP), physical function (PF), and social
      functioning (SF) domains had more than 20% change from baseline to 6 weeks and
      from 6 weeks to 6 months. Univariate and multivariate analyses were conducted to
      examine the association between preoperative anemia, transfusion and predischarge
      anemia on 6-month scores. RESULTS: On univariate analysis, preoperative
      hemoglobin less than 10.0 g/dL was associated with lower baseline prefall PMS,
      PF, RP, and SF scores. Predischarge anemia did not affect 6-month scores. On
      multivariate analysis, preoperative anemia (hemoglobin <10.0 g/dL) was associated
      with lower 6-month HHS, PMS, PF, and RP scores, whereas transfusion was not
      significant. CONCLUSION: Preoperative anemia (hemoglobin <10.0 g/dL) is
      associated with poorer physical function and HRQoL after hip fracture surgery.
      Perioperative blood transfusion and predischarge anemia had no effect.

PMID- 30091140
TI  - The impact of accommodating client preference in psychotherapy: A meta-analysis.
AB  - Client preferences in psychotherapy reflect specific conditions and activities
      that clients desire in their treatment, with increasing evidence pointing to
      preference accommodation as facilitating psychotherapy outcomes. This updated
      meta-analysis establishes the magnitude of the effect of client preference
      accommodation in psychotherapy. Based on data from 53 studies and over 16,000
      clients, preference accommodation was associated with fewer treatment dropouts
      (OR = 1.79) and more positive treatment outcomes (d = 0.28) than providing client
      with a nonpreferred treatment or psychotherapy condition. The preference effect
      was moderated by study design, timing and type of outcome measurement, and client
      diagnosis. It was not moderated by year of publication, treatment duration,
      preference type, treatment options, client age, client gender, client ethnicity,
      or client years of education. The authors provide a case example of preference
      accommodation and practice recommendations for working with client preferences.

PMID- 30091141
TI  - Effectiveness of Reciproc Blue in removing canal filling material and regaining
      apical patency.
AB  - AIM: To compare the efficiency of M-Wire Reciproc and Reciproc Blue instruments
      in the removal of root filling material and in their ability to regain apical
      patency through micro-computed tomographic (micro-CT) analysis. METHODOLOGY: Ten
      anatomically matched pairs of teeth, with a single oval-shaped straight canal,
      were selected and scanned in a micro-CT device. The root canals were prepared
      with M-Wire Reciproc R25 instruments and filled with gutta-percha and AH Plus
      sealer. The root canals were then randomly allocated into two groups (n = 10),
      according to the instrument used: M-Wire Reciproc and Reciproc Blue. The canals
      were retreated up to instrument sizes 25 and then 40 in both groups. The surface
      area and volume of residual filling material were assessed using micro-CT imaging
      after the retreatment procedures. The time required to remove the root fillings
      was recorded. Data were analysed statistically using t-test with a significance
      level of 5%. RESULTS: No significant difference (P > 0.05) was observed between
      the instruments in terms of the volume of residual root filling material. Apical
      enlargement from size 25 to 40 significantly improved the removal of filling
      materials (P < 0.05). It was possible to regain apical patency in all specimens
      from both M-Wire Reciproc and Reciproc Blue groups. No difference was observed in
      the time required to perform the retreatment between the instruments.
      CONCLUSIONS: Both M-Wire Reciproc and Reciproc Blue instruments were effective in
      removing filling materials from oval-shaped straight canals. Apical patency was
      reestablished in all specimens.

PMID- 30091142
TI  - Aging-related changes in quantity and quality of saliva: Where do we stand in our
      understanding?
AB  - : Saliva is crucial to oral processing of food and consequently is also related
      to the sensory and textural experience. It is often assumed that the secretion
      and properties of saliva change with age, which can result in dry mouth
      conditions, taste aberrations. Such changes may result in reduced nutrient intake
      and malnutrition besides adversely affecting the quality of life. Based on some
      recent research findings, this article reviews our current understandings on age
      dependent changes on quantity (bulk salivary flow rate) as well as quality of
      saliva (e.g., composition, viscosity, lubrication) in healthy elderly
      individuals. The review begins with a short introduction to histological changes
      of salivary glands upon aging. This is followed by covering different aspects of
      salivary changes with key articles highlighting decreased flow rate, increased
      ionic concentration, decreased calcium and mucin content in saliva of elderly
      subjects consequently affecting the oral coating and flavor perception. We also
      highlight issues in data associated with respect to variance in saliva collection
      protocols as well as factors influencing such results other than age, such as
      health conditions and polypharmacy. Clear gaps in literature have been
      highlighted with respect to lack of quantitative data in viscoelasticity,
      rheology, and lubrication properties of saliva in healthy elderly population and
      the potential impact of changes in these material properties on sensory and
      textural perception of food and consequently food intake. Such insights will not
      only have clinical implications for maintaining optimal oral health in elderly
      population but also serve to optimize food for elderly population. PRACTICAL
      APPLICATIONS: The population has undergone a fundamental change in its age
      structure globally, with a rapid increase in elderly population. Innovation of
      tailored foods is still in its early stage to satisfy the needs of growing aging
      population. One of the biggest challenges in such food product development is
      lack of adequate understanding and characterization of endogenous factors, that
      is, age-related changes in saliva, which may influence oral processing of food
      and subsequently nutrient intake. Aging affects the salivary glands and alters
      quantity (flow rate) and quality (e.g., ion and protein composition, rheology,
      tribology) of saliva. Thus, older adults may suffer from dry mouth, taste
      aberration, and poor oral hygiene, greatly affecting their quality of life. This
      review provides insights into how age versus other health conditions influence
      salivary properties. Understanding of age-dependent changes in salivary rheology
      and tribology will be of paramount importance to optimize food for elderly
      population.

PMID- 30091143
TI  - Review of toxicological effect of quantum dots on the liver.
AB  - In recent years, quantum dots (QDs) have potential applications in technology,
      research and medicine. The small particle size is coupled to their unique
      chemical and physical properties and their excellent fluorescence
      characteristics. A growing number of studies have shown that QDs are distributed
      to secondary organs through multiple pathways, while the liver is the main
      reservoir of QDs. Here, we review current liver toxicity studies of QDs in vivo
      and in vitro. Mechanisms of hepatotoxicity are discussed and the problem of
      extrapolating knowledge gained from cell-based studies into animal studies is
      highlighted. In this context, there still exists significant discrepancies
      between in vitro and in vivo results, and the specific toxicity mechanism remains
      unclear. The hepatotoxicities of QDs are the need for a unifying protocol for
      reliable and realistic toxicity reports.

PMID- 30091144
TI  - Pharmacokinetics of Phosphatidylethanol 16:0/20:4 in Human Blood After Alcohol
      Intake.
AB  - BACKGROUND: The purpose of this study was to characterize the pharmacokinetics of
      the phosphatidylethanol (PEth) 16:0/20:4 homolog in uncoagulated human blood
      samples taken from 18 participants in a clinical laboratory setting after
      consumption of 2 standard doses of ethanol (EtOH). METHODS: Male and female
      participants received either 0.4 or 0.8 g/kg oral doses of EtOH during a 15
      minute period. Blood samples were collected before and throughout 6 hours
      immediately after alcohol administration and then again at days 2, 4, 7, 11, and
      14 of the follow-up period. PEth 16:0/20:4 levels were quantified by high
      performance liquid chromatography with tandem mass spectrometry detection.
      RESULTS: (i) The increase in PEth 16:0/20:4 from baseline to maximum
      concentration was less than that of PEth 16:0/18:1 or PEth 16:0/18:2 homologs
      during the 6-hour period after EtOH administration; (ii) the mean half-life of
      PEth 16:0/20:4 was 2.1 +/- 3 (SD) days, which was shorter than the mean half-life
      of either PEth 16:0/18:1 or PEth 16:0/18:2, 7.6 +/- 3 (SD) or 6.8 +/- 4 (SD)
      days, respectively. CONCLUSIONS: The pharmacokinetics of PEth 16:0/20:4 in whole
      blood samples is detectable after alcohol consumption and differs in amount
      synthesized and rate of elimination versus PEth 16:0/18:1 and 16:0/18:2.
      Measuring the concentrations of these 3 homologs has the potential to provide
      more information about the amount and time frame of alcohol consumption than any
      one alone.

PMID- 30091145
TI  - Three-dimensional kinematics of the canine carpal bones imaged with computed
      tomography after ex vivo axial limb loading and palmar ligament transection.
AB  - OBJECTIVE: To describe normal antebrachiocarpal joint kinematic motion during
      axial loading and to describe the effect of palmar radiocarpal ligament (PRL) and
      palmar ulnocarpal ligament (PUL) transection on this motion. SAMPLE POPULATION:
      Ten forelimbs from 5 adult greyhound cadavers. METHODS: Limbs were placed in a
      custom jig and computed tomography images of limbs were obtained in neutral and
      extended positions. The translation and rotation of the intermedioradiocarpal
      bone (RCB), ulnar carpal bone, and accessory carpal bone were described relative
      to the radius through rigid body motion analysis. Kinematic and load analysis was
      repeated after sequential transection of the PRL and the PUL. RESULTS: Sagittal
      plane extension with a lesser component of valgus motion was found in all
      evaluated carpal bones. RCB supination was also detected during extension.
      Compared with the normal intact limb, transection of either or both the PRL and
      the PUL did not influence mean translation or rotation data or limb load.
      However, the transection of the PRL and the PUL increased the variance in
      rotation data compared with intact limb. CONCLUSION: This study describes normal
      antebrachiocarpal kinematics as a foundation for determining carpal functional
      units. During axial loading, the PRL and the PUL may function to guide consistent
      motion in extension and flexion as well as pronation and supination. CLINICAL
      SIGNIFICANCE: Three-dimensional carpal kinematic analyses may improve our
      understanding of carpal injury and facilitate the development of novel treatments
      techniques.

PMID- 30091146
TI  - Vitamin A and beta (beta)-carotene supplementation for cystic fibrosis.
AB  - BACKGROUND: People with cystic fibrosis (CF) and pancreatic insufficiency are at
      risk of a deficiency in fat-soluble vitamins, including vitamin A. Vitamin A
      deficiency predominantly causes eye and skin problems, while excessive levels of
      vitamin A can harm the respiratory and skeletal systems in children and interfere
      with the metabolism of other fat-soluble vitamins. Most CF centres administer
      vitamin A as supplements to reduce the frequency of vitamin A deficiency in
      people with CF and to improve clinical outcomes such as growth, although the
      recommended dose varies between different guidelines. Thus, a systematic review
      on vitamin A and vitamin A-like supplementation (carotenes or other retinoids) in
      people with CF would help guide clinical practice. This is an update of an
      earlier Cochrane Review. OBJECTIVES: To determine if supplementation with vitamin
      A, carotenes or other retinoid supplements in children and adults with CF reduces
      the frequency of vitamin A deficiency disorders, improves general and respiratory
      health and affects the frequency of vitamin A toxicity. SEARCH METHODS: We
      searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Cystic Fibrosis
      Trials Register compiled from electronic database searches and handsearching of
      journals and conference abstract books. Additionally we searched several ongoing
      trials registries, including ClinicalTrials.gov, the WHO International Clinical
      Trials Registry Platform and the International Standard Randomised Controlled
      Trial Number Registry.Most recent database searches: 01 June 2018. SELECTION
      CRITERIA: All randomised or quasi-randomised controlled studies comparing all
      preparations of oral vitamin A, carotenes or retinoids (or in combination), used
      as a supplement compared to placebo at any dose, for at least three months, in
      people with CF (diagnosed by sweat tests or genetic testing) with and without
      pancreatic insufficiency. DATA COLLECTION AND ANALYSIS: Two authors individually
      assessed study quality and extracted data on outcome measures. The authors
      assessed the quality of the evidence using the GRADE system. Investigators were
      contacted to retrieve missing quantitative data. MAIN RESULTS: No studies of
      vitamin A or other retinoid supplementation were eligible for inclusion. However,
      one randomised study of beta (beta)-carotene supplementation involving 24 people
      with CF who were receiving pancreatic enzyme substitution was included. The study
      compared successive beta-carotene supplementation periods (high dose followed by
      low dose) compared to placebo. The results for the low-dose supplementation
      period should be interpreted with caution, due to the lack of a wash-out period
      after the high-dose supplementation.The included study did not report on two of
      the review's primary outcomes (vitamin A deficiency disorders and mortality);
      results for our third primary outcome of growth and nutritional status (reported
      as z score for height) showed no difference between supplementation and placebo,
      mean difference (MD) -0.23 (95% confidence interval (CI) -0.89 to 0.43) (low
      quality evidence). With regards to secondary outcomes, supplementation with high
      dose beta-carotene for three months led to significantly fewer days of systemic
      antibiotics required to treat pulmonary exacerbations, compared to controls, MD 
      15 days (95% CI -27.60 to -2.40); however, this was not maintained in the second
      three-month section of the study when the level of beta-carotene supplementation
      was reduced, MD -8 days (95% CI -18.80 to 2.80) (low-quality evidence). There
      were no statistically significant effects between groups in lung function (low
      quality evidence) and no adverse events were observed (low-quality evidence).
      Supplementation affected levels of beta-carotene in plasma, but not vitamin A
      levels. The study did not report on quality of life or toxicity. AUTHORS'
      CONCLUSIONS: Since no randomised or quasi-randomised controlled studies on
      retinoid supplementation were identified, no conclusion on the supplementation of
      vitamin A in people with CF can be drawn. Additionally, due to methodological
      limitations in the included study, also reflected in the low-quality evidence
      judged following the specific evidence grading system (GRADE), no clear
      conclusions on beta-carotene supplementation can be drawn. Until further data are
      available, country- or region-specific guidelines regarding these practices
      should be followed.

PMID- 30091147
TI  - Needle size for vaccination procedures in children and adolescents.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in 2015. The
      conclusions have not changed.Hypodermic needles of different sizes (gauges and
      lengths) can be used for vaccination procedures. The gauge (G) refers to the
      outside diameter of the needle tubing. The higher the gauge number, the smaller
      the diameter of the needle (e.g. a 23 G needle is 0.6 mm in diameter, whereas a
      25 G needle is 0.5 mm in diameter). Many vaccines are recommended for injection
      into muscle (intramuscularly), although some are delivered subcutaneously (under
      the skin) and intradermally (into skin). Choosing an appropriate length and gauge
      of a needle may be important to ensure that a vaccine is delivered to the
      appropriate site and produces the maximum immune response while causing the least
      possible harm. Guidelines conflict regarding the sizes of needles that should be
      used for vaccinating children and adolescents. OBJECTIVES: To assess the effects
      of using needles of different sizes for administering vaccines to children and
      adolescents on vaccine immunogenicity (the ability of the vaccine to elicit an
      immune response), procedural pain, and other reactogenicity events (adverse
      events following vaccine administration). SEARCH METHODS: We updated our searches
      of CENTRAL, MEDLINE, Embase, and CINAHL to October 2017. We also searched
      proceedings of vaccine conferences and two trials registers. SELECTION CRITERIA:
      Randomised controlled trials evaluating the effects of using hypodermic needles
      of any gauge or length to administer any type of vaccine to people aged from
      birth to 24 years. DATA COLLECTION AND ANALYSIS: Three review authors
      independently extracted trial data and assessed the risk of bias. We contacted
      trial authors for additional information. We rated the quality of evidence using
      the GRADE system. MAIN RESULTS: We included five trials involving 1350
      participants in the original review. The updated review identified no new trials.
      The evidence from two small trials (one trial including infants and one including
      adolescents) was insufficient to allow any definitive statements to be made about
      the effects of the needles evaluated in the trials on vaccine immunogenicity and
      reactogenicity.The remaining three trials (1135 participants) contributed data to
      comparisons between 25 G 25 mm, 23 G 25 mm, and 25 G 16 mm needles. These trials
      included infants predominantly aged from two to six months undergoing
      intramuscular vaccination in the anterolateral thigh using the World Health
      Organization (WHO) injection technique (skin stretched flat, needle inserted at a
      90 degrees  angle and up to the needle hub in healthy infants). The vaccines
      administered were combination vaccines containing diphtheria, tetanus, and whole
      cell pertussis antigens (DTwP). In some trials, the vaccines also contained
      Haemophilus influenzae type b (DTwP-Hib) and hepatitis B (DTwP-Hib-Hep B) antigen
      components.Primary outcomesIncidence of vaccine-preventable diseases: No trials
      reported this outcome.Procedural pain and crying: Using a wider gauge 23 G 25 mm
      needle may slightly reduce procedural pain (low-quality evidence) and probably
      leads to a slight reduction in the duration of crying time immediately after
      vaccination (moderate-quality evidence) compared with a narrower gauge 25 G 25 mm
      needle (one trial, 320 participants). The effects are probably not large enough
      to be clinically relevant.Secondary outcomesImmune response: There is probably
      little or no difference in immune response, defined in terms of the proportion of
      seroprotected infants, between use of 25 G 25 mm, 23 G 25 mm, or 25 G 16 mm
      needles to administer a series of three doses of a DTwP-Hib vaccine at ages two,
      three, and four months (moderate-quality evidence, one trial, numbers of
      participants in analyses range from 309 to 402. The immune response to the
      pertussis antigen was not measured).Severe and non-severe local reactions: 25 mm
      needles (either 25 G or 23 G) probably lead to fewer severe and non-severe local
      reactions after DTwP-Hib vaccination compared with 25 G 16 mm needles (moderate
      quality evidence, one trial, 447 to 458 participants in analyses). We estimate
      that one fewer infant will experience a severe local reaction (extensive redness
      and swelling) after the first vaccine dose for every 25 infants vaccinated with
      the longer rather than the shorter needle (number needed to treat for an
      additional beneficial outcome (NNTB) with a 25 G 25 mm needle: 25 (95% confidence
      interval (CI) 15 to 100); NNTB with a 23 G 25 mm needle: 25 (95% CI 17 to 100)).
      We estimate that one fewer infant will experience a non-severe local reaction
      (any redness, swelling, tenderness, or hardness (composite outcome)) at 24 hours
      after the first vaccine dose for every 5 or 6 infants vaccinated with a 25 mm
      rather than a 16 mm needle (NNTB with a 25 G 25 mm needle: 5 (95% CI 4 to 10);
      NNTB with a 23 G 25 mm needle: 6 (95% CI 4 to 13)). The results are similar after
      the second and third vaccine doses.Using a narrow gauge 25 G 25 mm needle may
      produce a small reduction in the incidence of local reactions after each dose of
      a DTwP vaccine compared with a wider gauge 23 G 25 mm needle, but the effect
      estimates are imprecise (low-quality evidence, two trials, 100 to 459
      participants in analyses).Systemic reactions: The comparative effects of 23 G 25
      mm, 25 G 25 mm, and 25 G 16 mm needles on the incidence of postvaccination fever
      and other systemic events such as drowsiness, loss of appetite, and vomiting are
      uncertain due to the very low quality of the evidence. AUTHORS' CONCLUSIONS:
      Using 25 mm needles (either 23 G or 25 G) for intramuscular vaccination
      procedures in the anterolateral thigh of infants using the WHO injection
      technique probably reduces the occurrence of local reactions while achieving a
      comparable immune response to 25 G 16 mm needles. These findings are applicable
      to healthy infants aged two to six months receiving combination DTwP vaccines
      with a reactogenic whole-cell pertussis antigen component. These vaccines are
      predominantly used in low- and middle-income countries. The applicability of the
      findings to vaccines with acellular pertussis components and other vaccines with
      different reactogenicity profiles is uncertain.

PMID- 30091149
TI  - Association of albumin and cholesterol levels with incidence of hypoglycaemia in
      people admitted to general internal medicine units.
AB  - AIM: To study the association between serum albumin and cholesterol levels at
      hospital admission and incident hypoglycaemia among people admitted to internal
      medicine units. METHODS: In this cross-sectional analysis, we examined the
      electronic medical records of people hospitalized in internal medicine
      departments. Data extracted included all glucose measurements as well as serum
      albumin and cholesterol, which were measured upon admission. A hypoglycaemia
      event was recorded for a given person if at least one glucose measurement of <=
      3.9 mmol/l was recorded during the hospital stay. Regression analysis was used to
      determine which clinical measures predict hypoglycaemia. RESULTS: During the
      acquisition period, 45 224 people (mean age 68.9 +/- 17.8 years, 49.4% male,
      21.1% diabetes mellitus) were discharged from internal medicine units.
      Hypoglycaemia was documented in 7.5% of these individuals (15.4% of people with
      diabetes vs. 5.5% of those without; P < 0.001). Logistic regression showed that
      both serum albumin [odds ratio (OR) 0.908, 95% confidence interval (CI) 0.896
      0.919; P < 0.001) and cholesterol (OR 0.938, 95% CI 0.896-0.981; P = 0.005] were
      significantly associated with incident hypoglycaemia. Results remained
      significant even after controlling for age, sex, average glucose during
      hospitalization, length of hospital stay, acute infection upon admission,
      diabetes status, haemoglobin, white blood cell count and C-reactive levels. A
      combination of hypoalbuminaemia (< 35 g/l) and hypocholesterolaemia (< 3.37
      mmol/l) upon admission greatly increased the risk of incident hypoglycaemia (OR
      2.544, 95% CI 2.096-3.088; P < 0.001). CONCLUSION: Hypoalbuminaemia and
      hypocholesterolaemia predict incident hypoglycaemia in the hospital setting among
      people with and without diabetes mellitus.

PMID- 30091148
TI  - 2,4-Dichlorophenol induces DNA damage through ROS accumulation and GSH depletion
      in goldfish Carassius auratus.
AB  - 2,4-Dichlorophenol (2,4-DCP) is one of the most abundant chlorophenols in the
      aquatic environment and has been frequently detected in surface waters. Although
      ecological and cellular toxicity of 2,4-DCP has aroused the public concern, few
      reports focus on the genotoxicity, especially on DNA double strand breaks (DSBs),
      of 2,4-DCP in fish. The present study aims to explore the genotoxic effect of 2,4
      DCP on DSBs in goldfish Carassius auratus and to further elucidate its potential
      mechanism. The results showed that 2,4-DCP significantly induced DSBs (detected
      by neutral comet assay) in erythrocytes and hepatocytes of goldfish in a dose
      dependent manner, indicating a genotoxicity of 2,4-DCP on fish. The total
      antioxidant capability and the content of reduced glutathione (GSH) were
      significantly decreased, while the level of reactive oxygen species (ROS) was
      significantly increased in a dose-dependent manner in erythrocytes and
      hepatocytes, suggesting an oxidative stress caused by 2,4-DCP in fish. N-acetyl-l
      cysteine, a precursor of GSH and a ROS scavenger, significantly impaired 2,4-DCP
      induced ROS overproduction and DSBs, which proves that ROS accumulation and GSH
      depletion are involved in 2,4-DCP-induced DNA damage in fish. Environ. Mol.
      Mutagen. 59:798-9, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30091150
TI  - Revision of assessment toolkits for improving the diagnosis of Lewy body
      dementia: The DIAMOND Lewy study.

PMID- 30091151
TI  - Psychologists' Willingness to Provide Services to Individuals at Risk of Suicide.
AB  - OBJECTIVE: This study examined psychologists' willingness to accept a new client
      into their private practice as a function of the client's clinical presentation
      (with or without overt suicidality). Psychologists' openness to working with a
      client at risk of suicide was evaluated in the context of potential barriers to
      treatment provision, such as practitioners' endorsement of stigmatizing
      attitudes, concerns over liability and inadequate training, and limited access to
      community resources. METHOD: Eighty-six licensed psychologists practicing within
      the United States were surveyed via e-mail and randomly assigned to one of two
      conditions, consisting of exposure to a vignette describing either a client
      reporting current suicidal ideation and a history of attempts or a client without
      explicitly elevated suicide risk. All participants were asked to complete a
      questionnaire assessing their likelihood of accepting the hypothetical client
      into their practice and examining possible explanations for disinclination to
      provide treatment. RESULTS: Psychologists were less willing to work with a client
      experiencing suicidality than an individual without elevated suicide risk. Those
      indicating a reluctance to provide services reported greater concerns over the
      adequacy of their suicide-related skills and training and fewer resources in the
      community. CONCLUSIONS: Recommendations for improving the responsiveness of
      private practitioners are provided, with an emphasis on enhancing clinical
      training and increasing the availability and accessibility of mental health
      resources.

PMID- 30091152
TI  - Growth-defense trade-off regulated by hormones in grass plants growing under
      different grazing intensities.
AB  - Herbivory creates conflicts between a plant's need to allocate resources for
      growth and defense. It is not yet clear how plants rebalance resource utilization
      between growth and defense in response to increasing grazing intensity. We
      measured characteristics of the primary and secondary metabolism of Leymus
      chinensis at five levels of grazing intensity (control, light, moderate, heavy
      and extremely heavy). Furthermore, we evaluated hormone signaling by quantifying
      the impact of key hormones on plant growth and defense. Under light grazing
      intensity, indole-3-acetic acid and jasmonates appeared to promote the growth of
      L. chinensis through a high photosynthetic rate, high water-use efficiency and
      high soluble protein contents, whereas abscisic acid decreased these properties.
      Under moderate grazing intensity, L. chinensis had a low photosynthetic capacity
      but greater production of secondary metabolites (tannins, total flavonoids and
      total phenols), possibly induced by salicylic acid. When the grazing pressure
      further intensified, L. chinensis translocated more carbohydrates to its roots in
      order to survive and regrow. Leymus chinensis therefore exhibited a trade-off
      between growth and defense in order to survive and reproduce under herbivory.
      Plants developed different mechanisms to enhance their grazing tolerance by means
      of hormonal regulation.

PMID- 30091153
TI  - Next-Generation Narrow-Band Green-Emitting RbLi(Li3 SiO4 )2 :Eu2+ Phosphor for
      Backlight Display Application.
AB  - The discovery of high efficiency narrow-band green-emitting phosphors is a major
      challenge in backlighting light-emitting diodes (LEDs). Benefitting from highly
      condensed and rigid framework structure of UCr4 C4 -type compounds, a next
      generation narrow green emitter, RbLi(Li3 SiO4 )2 :Eu2+ (RLSO:Eu2+ ), has emerged
      in the oxide-based family with superior luminescence properties. RLSO:Eu2+
      phosphor can be efficiently excited by GaN-based blue LEDs, and shows green
      emission at 530 nm with a narrow full width at half maximum of 42 nm, and very
      low thermal quenching (103%@150  degrees C of the integrated emission intensity
      at 20  degrees C), however its chemical stability needs to be improved later. The
      white LED backlight using optimized RLSO:8%Eu2+ phosphor demonstrates a high
      luminous efficacy of 97.28 lm W-1 and a wide color gamut (107% National
      Television System Committee standard (NTSC) in Commission Internationale de
      L'Eclairage (CIE) 1931 color space), suggesting its great potential for
      industrial applications as liquid crystal display (LCD) backlighting.

PMID- 30091155
TI  - Contribution to the discussion of "When should meta-analysis avoid making hidden
      normality assumptions?"

PMID- 30091154
TI  - Association between comfort and needs of ICU patients' family members: A cross
      sectional study.
AB  - AIMS AND OBJECTIVE: To identify the family members' level of comfort and needs
      and to analyse the sociodemographic/clinical variables that influence this
      association. BACKGROUND: The needs of family members are important considerations
      in intensive care units. In this context, the needs will be assessed in five
      dimensions: information, safety, proximity, support and comfort. This study
      describes the association between comfort and needs of ICU patients' family
      members. DESIGN: Cross-sectional study developed at the adult ICU of a hospital
      within the state of Sao Paulo, in the period from July-September 2016. METHODS:
      We used the Critical Care Family Needs Inventory (INEFTI) Portuguese version and
      the comfort scale for critical care patient relatives (ECONF). RESULTS: In
      relation to INEFTI, the relatives assigned high importance to the needs (Median =
      167), but not all of them satisfied (Median = 151). The comfort was low (Median =
      3.6), and support was the most affected domain (Median = 2.78). The multivariate
      analysis indicated variables that influenced the comfort: marital status (beta =
      0.80; p < 0.01), disease severity (beta = 0.03; p = 0.04), female sex (beta =
      0.34; p = 0.01), highest educational attainment (beta = 0.37; p < 0.01),
      employment status (beta = 0.81; p < 0.01) and kinship (beta = 0.34; p < 0.01).
      Concerning the INEFTI scores, only age was statistically significant for
      importance (beta = 0.16; p < 0.01) and satisfaction (beta = -0.29; p = 0.04) of
      the family members' needs. In the multiple correspondence analysis, different
      proximities were identified for the variables comfort and needs. Greater ECONF
      scores were associated with family members with a higher educational degree,
      whose patients were stable, who attributed high levels of importance to the needs
      and who were housewives. CONCLUSIONS: Family members have needs that are
      considered important but not fully met. No direct correspondence between comfort
      and family needs was identified. RELEVANCE TO CLINICAL PRACTICE: In view of the
      lack of studies involving family members' comfort and needs, we believe that
      these results can guide nursing proposals focused on the family members, in line
      with the associations found among different variables that influenced the
      results.

PMID- 30091156
TI  - Endometrial thickness in modified natural-cycle frozen-thawed embryo transfer
      cycles: Should we ignore the red traffic lights?

PMID- 30091157
TI  - 2D Metal Oxyhalide-Derived Catalysts for Efficient CO2 Electroreduction.
AB  - Electrochemical reduction of CO2 is a compelling route to store renewable
      electricity in the form of carbon-based fuels. Efficient electrochemical
      reduction of CO2 requires catalysts that combine high activity, high selectivity,
      and low overpotential. Extensive surface reconstruction of metal catalysts under
      high productivity operating conditions (high current densities, reducing
      potentials, and variable pH) renders the realization of tailored catalysts that
      maximize the exposure of the most favorable facets, the number of active sites,
      and the oxidation state all the more challenging. Earth-abundant transition
      metals such as tin, bismuth, and lead have been proven stable and product
      specific, but exhibit limited partial current densities. Here, a strategy that
      employs bismuth oxyhalides as a template from which 2D bismuth-based catalysts
      are derived is reported. The BiOBr-templated catalyst exhibits a preferential
      exposure of highly active Bi ( 11-0 ) facets. Thereby, the CO2 reduction reaction
      selectivity is increased to over 90% Faradaic efficiency and simultaneously
      stable current densities of up to 200 mA cm-2 are achieved-more than a twofold
      increase in the production of the energy-storage liquid formic acid compared to
      previous best Bi catalysts.

PMID- 30091158
TI  - Important issues in plant tissues analyses by HR-MAS NMR.
AB  - INTRODUCTION: High-resolution magic-angle spinning nuclear magnetic resonance (HR
      MAS NMR) spectroscopy enables the analysis of the metabolic profile of plant and
      animal tissues under close to natural conditions, as well as of other
      heterogeneous natural or synthetic materials. Neither sample pretreatment is
      required after fragmentation nor powdering of the sample before insertion into
      the rotor. However, the efficiency of the method depends strongly on the sample
      preparation, rotor insertion procedure, and analysis conditions. OBJECTIVE: To
      identify some of the variables that affect the spectral data and to propose
      solutions that minimise their impact on the quality of the analyses and results.
      METHODS: Dried plant tissues were powdered, weighed, and homogenised in a 50 MUL
      rotor with an optimised volume of deuterated solvent and sample in order to
      prevent material from escaping during spacer insertion, avoiding variations in
      magnetic susceptibility. Factors affecting the quality of HR-MAS NMR analysis
      such as particle size, sample and solvent amounts, solvent polarity, swelling
      time, rotor manipulation and pulse sequence setting were evaluated. RESULTS: A
      strong correlation was observed between the signal area and the particle size of
      the powdered sample. The spectral profile varied depending on the deuterated
      solvent used. An incubation period was necessary to achieve adequate swelling of
      the sample and to ensure good data reproducibility. Proper sealing of the rotor,
      number of cycles and tau time on cpmgpr1d pulse sequence were found to affect the
      signal areas. CONCLUSION: The study highlights the need for standardised sample
      preparation and instrumental setup protocols in order to achieve high
      reproducibility and obtain reliable data from HR-MAS NMR analyses.

PMID- 30091159
TI  - [6]-Gingerol-induced cell cycle arrest, reactive oxygen species generation, and
      disruption of mitochondrial membrane potential are associated with apoptosis in
      human gastric cancer (AGS) cells.
AB  - Ginger (Zingiber officinale Roscoe), a monocotyledonous herb, is widely used as
      an herbal medicine owing to the phytoconstituents it possesses. In the current
      study, the quantity of [6]-gingerol, the major phenolic ketone, in the fresh
      ginger and dried ginger rhizome was found to be 6.11 ug/mg and 0.407 ug/mg.
      Furthermore, [6]-gingerol was assessed for its antiapoptotic effects in human
      gastric adenocarcinoma (AGS) cells evidenced by acridine orange/ethidium bromide
      staining technique and Annexin-V assay. An increase in reactive oxygen species
      (ROS) generation led to a decrease in mitochondrial membrane potential (MMP) and
      subsequent induction of apoptosis. Results disclose that perturbations in MMP are
      associated with deregulation of Bax/Bcl-2 ratio at protein level, which leads to
      upregulation of cytochrome-c triggering the caspase cascade. These enduringly
      suggest that [6]-gingerol can be effectively used for targeting the mitochondrial
      energy metabolism to manage gastric cancer cells.

PMID- 30091160
TI  - Sleep Disorders and Migraine: Review of Literature and Potential Pathophysiology
      Mechanisms.
AB  - Migraine shares a complex and poorly understood relationship with sleep. Patients
      consistently report poor sleep prior to migraine attacks and during them,
      identifying poor sleep as a migraine trigger. However, anecdotally, sleep is
      reported to serve a therapeutic role in terminating headache. Are the
      associations between migraine and sleep simply the result of various
      bidirectional relationships? A growing body of evidence suggests there may be a
      common underlying etiology as well. Our objective was to review studies of sleep
      and migraine from the last 2 decades utilizing validated subjective and objective
      measures of sleep and to explore potential mechanisms underlying this complex
      relationship by incorporating recent advances in neuroscience. We specifically
      focus on insomnia, obstructive sleep apnea, parasomnias, sleep related movement
      disorders, and REM sleep related disorders and their relationship to migraine.
      Parts of brainstem-cortical networks involved in sleep physiology are
      unintentionally being identified as important factors in the common migraine
      pathway. Recent discoveries on anatomic localization (the hypothalamus as a key
      and early mediator in the pathophysiology of migraine), common mediating
      signaling molecules (such as serotonin and dopamine), and the discovery of a new
      CNS waste removal system, the glymphatic system, all point to a common
      pathophysiology manifesting in migraine and sleep problems.

PMID- 30091162
TI  - DNA vaccine ROP29 from Toxoplasma gondii containing R848 enhances protective
      immunity in mice.
AB  - AIMS: Toxoplasma gondii is an intracellular parasite that causes a global
      epidemic parasitic disease. Studies using DNA vaccines for the control of
      toxoplasmosis have made considerable progress. ROP proteins were proven to be
      excellent candidates for T. gondii DNA vaccine development. METHODS AND RESULTS:
      Here, a ROP29 DNA vaccine was successfully produced and injected into mice in
      combination with R848 to evaluate its ability to provide protection against T.
      gondii challenge. Compared with other mice, the mice injected with R848/pROP29
      produced higher levels of IgG, IgG2a, interleukin (IL)-12, and interferon gamma
      (IFN-gamma). Moreover, after a challenge of 20 T. gondii cysts, the number of
      brain cysts was lower in the R848/pROP29-immunized mice than in the other
      experimental mice. CONCLUSIONS: R848 could improve the productions of IL-12 and
      IFN-gamma, thus enhancing the immune responses stimulated by the pROP29 DNA
      vaccine.

PMID- 30091161
TI  - Independent predictors of mortality in adolescents ascertained for conduct
      disorder and substance use problems, their siblings and community controls.
AB  - BACKGROUND AND AIMS: Adolescents with conduct and substance use problems are at
      increased risk for premature mortality, but the extent to which these risk
      factors reflect family- or individual-level differences and account for shared or
      unique variance is unknown. This study examined common and independent
      contributions to mortality hazard in adolescents ascertained for conduct disorder
      (CD) and substance use disorder (SUD), their siblings and community controls,
      hypothesizing that individual differences in CD and SUD severity would explain
      unique variation in mortality risk beyond that due to clinical/control status and
      demographic factors. DESIGN: Mortality analysis in a prospective study (Genetics
      of Antisocial Drug Dependence Study) that began in 1993. SETTING: Multi-site
      sample recruited in San Diego, California and Denver, Colorado, USA.
      PARTICIPANTS: A total of 1463 clinical probands were recruited through the
      juvenile correctional system, court-mandated substance abuse treatment programs
      and correctional schools, along with 1399 of their siblings, and 904 controls.
      MEASUREMENTS: Mortality and cause-of-death were assessed via National Death Index
      search (released October, 2017). FINDINGS: There were 104 deaths documented among
      3766 (1168 female) adolescents and young adults (average age 16.79 years at
      assessment, 32.69 years at death/censoring). Mortality hazard for clinical
      probands and their siblings was 4.99 times greater than that of controls (95%
      confidence interval = 2.40-10.40; P < 0.001). After accounting for demographic
      characteristics, site, clinical status, familial dependence and shared
      contributions of CD and SUD, CD independently predicted mortality hazard, whereas
      SUD severity did not. CONCLUSIONS: In the United States, youth with conduct and
      substance use disorders and their siblings face far greater risk of premature
      death than demographically similar community controls. In contrast to substance
      use disorder severity, conduct disorder is a robust predictor of unique variance
      in all-cause mortality hazard beyond other risk factors.

PMID- 30091163
TI  - Haematopoietic stem cell transplantation for mucopolysaccharidosis type VII: A
      case report.
AB  - Mucopolysaccharidosis type VII (MPS VII) is an inherited disease characterized by
      the cellular accumulation of undegraded GAGs due to the deficiency of the
      lysosomal enzyme beta-glucuronidase. We describe a case of a 2-year-old female
      affected by a moderate form of MPS VII and submitted twice to HSCT with the aim
      of stabilizing skeletal problems and preventing neurocognitive alterations. The
      child underwent a second transplantation due to the rejection of the graft after
      a reduced-intensity conditioning in the first transplant. A myeloablative regimen
      allowed to achieve a stable full donor engraftment and normal enzyme levels
      during the 6 years of follow-up. Clinically, we observed stabilization of
      skeletal deformities and normal neurocognitive development. This is one of the
      few reports of mucopolysaccharidosis type VII treated with allogeneic HSCT.

PMID- 30091164
TI  - Hepatitis C treatment for difficult to access populations; can telementoring (as
      distinct from telemedicine) help?
AB  - INTRODUCTION: Hepatitis C (HCV) is curable, treatment of difficult to access
      populations (DTAPs) presents unique challenges. Project ECHO(r) (PE), a tele
      mentoring program, adopted to support clinicians treating DTAPs. AIMS: Determine
      if the PE model supports primary care clinicians treating HCV. Compare cohort of
      PE patients with those in a tertiary liver clinic (TLC). METHODS: Weekly PE group
      video conferences were conducted. Clinical information, laboratory indices,
      psychosocial elements, and treatment outcomes including Sustained Virological
      Response (SVR) data were recorded in the first 100 consecutive cases and
      retrospectively compared to 100 consecutive patients seen at a tertiary liver
      clinic from July 2016 to April 2017. RESULTS: Some patient characteristics were
      similar between PE and TLC: gender (72% male vs 75% male: p=0.23), median age (45
      vs 50, p=0.344), proportion of treatment naive patients (95.0% vs 90.9%).
      Treatment for HCV was commenced in 78% of the PE patients and 81% of the TLC
      patients. 67 of the TLC patients and 60 PE patients have confirmed SVR. PE
      patients are more likely to have ongoing substance use (44% vs 17% p<0.001),
      active IVDU (32% vs 17% p<0.001) and polysubstance abuse (26% vs 7% p<0.001) and
      were more likely to be taking opioid substitution therapy (OST) (74% vs 20%
      p<0.001). Indigenous patients were three times more greatly represented in PE
      (15% vs 5% p = 0.018). CONCLUSION: Project ECHO(r) is an effective model to
      support primary healthcare providers treating HCV in DTAPs with similar rates of
      treatment uptake and SVR compared to patients in TLCs This article is protected
      by copyright. All rights reserved.

PMID- 30091165
TI  - l-arginine protects against oxidative damage induced by T-2 toxin in mouse Leydig
      cells.
AB  - To explore the protective mechanism of l-arginine against T-2 toxin-induced
      oxidative damage in mouse Leydig cells, Leydig cells were isolated and cultured
      with control, T-2 toxin (10 nM), l-arginine (0.25, 0.5, and 1.0 mM), and T-2
      toxin (10 nM T-2 toxin) with l-arginine (0.25, 0.5, or 1.0 mM) for 24 hours.
      Cells and supernatants were harvested to examine cell viability, activities, and
      messenger RNA (mRNA) expression of glutathione peroxidase (GSH-Px), superoxide
      dismutase (SOD), and catalase (CAT), malondialdehyde (MDA) content, and DNA
      damage. Results showed that T-2 toxin significantly reduced cell viability,
      improved MDA content and DNA damage, and decreased activities and mRNA expression
      of GSH-Px, SOD, and CAT. However, l-arginine reduced T-2 toxin-induced oxidative
      damage and tended to maintain normal levels. Furthermore, l-arginine upregulated
      mRNA expressions of GSH-Px, SOD, and CAT. Collectively, l-arginine, due to its
      antioxidative ability, could ameliorate T-2 toxin-induced cytotoxicities in mouse
      Leydig cells by regulating oxidative stress.

PMID- 30091166
TI  - Impact of performance status and transfusion dependency on outcome of patients
      with myelodysplastic syndrome, acute myeloid leukemia and chronic myelomonocytic
      leukemia treated with azacitidine (PIAZA study).
AB  - OBJECTIVE: Azacitidine (Vidaza(r) ) is the standard treatment for patients with
      higher-risk myelodysplastic syndromes (MDS) not eligible for allogeneic stem cell
      transplantation. In the noninterventional study PIAZA, we evaluated the
      effectiveness and safety of azacitidine treatment in 149 patients with higher
      risk MDS, chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML)
      in routine clinical practice. METHOD: Patients were treated according to
      physician's discretion. Besides evaluation of safety and effectiveness, impact of
      covariates on progression-free survival (PFS) was assessed. RESULTS: Median age
      of patients was 75 years. 61.1% of patients were diagnosed with MDS, 31.5% with
      AML and 7.4% with CMML. Patients were treated with azacitidine for a median of
      seven cycles. Median PFS was 10.9 months. Median OS was 14.1 months. Two-year
      survival rate was 28.9%. 45.9% of patients showed CR or PR. Stable and
      progressive disease were observed in 37.2% and 8% of patients, respectively.
      Transfusion independence was reported in 64 of 89 patients. Eastern cooperative
      oncology group (ECOG) performance status (PS) and red blood cell (RBC)
      transfusion before azacitidine therapy were identified as predictive factors for
      PFS. CONCLUSION: In conclusion, we estimated the duration of PFS in a real-world
      setting and identified ECOG PS and RBC transfusion as predictive factors for PFS.
      The safety of azacitidine showed a similar profile as demonstrated in the pivotal
      clinical trials.

PMID- 30091167
TI  - Nido-Carboranes: Donors for Thermally Activated Delayed Fluorescence.
AB  - An approach to the design of nido-carborane-based luminescent compounds that can
      exhibit thermally activated delayed fluorescence (TADF) is proposed. 7,8-Dicarba
      nido-undecaboranes (nido-carboranes) having various 8-R groups (R=H, Me, i-Pr,
      Ph) are appended to the meta or para position of the phenyl ring of the
      dimesitylphenylborane (PhBMes2 ) acceptor, forming donor-acceptor compounds (nido
      m1-m4 and nido-p1-p4). The bulky 8-R group and meta substitution of the nido
      carborane are essential to attain a highly twisted arrangement between the donor
      and acceptor moieties, leading to a very small energy splitting between the
      singlet and triplet excited states (DeltaEST <0.05 eV for nido-m2, -m3, and -p3).
      These compounds exhibit efficient TADF with microsecond-range lifetimes. In
      particular, nido-m2 and -m3 display aggregation-induced emission (AIE) with TADF
      properties.

PMID- 30091168
TI  - Comparison of the Fit of Lithium Disilicate Crowns made from Conventional,
      Digital, or Conventional/Digital Techniques.
AB  - PURPOSE: To evaluate the fit of single crowns fabricated using conventional,
      digital, or cast digitization methods. MATERIALS AND METHODS: One subject with a
      peg-shaped maxillary lateral incisor was selected in this study. Tooth
      preparation for an all-ceramic crown was performed and 10 conventional poly(vinyl
      siloxane) impressions, and 10 digital impressions using an intraoral scanner were
      made. Each working cast was scanned using a laboratory scanner and an intraoral
      scanner. Four groups were tested Group 1: conventional impressions. Group 2: cast
      laboratory scans. Group 3: cast scans using intraoral scanner. Group 4: direct
      intraoral scans. For group 1, heat-pressed glass ceramic crowns (IPS e.max Press)
      were fabricated using casts produced from the conventional impressions. For
      groups 2-4, crowns were milled using ceramic blocks (IPS e.max CAD). Ten crowns
      were fabricated for each group. Marginal and internal gaps were measured using a
      replica technique. Replicas were sectioned mesiodistally and buccolingually and
      were observed under a stereomicroscope. Three measurements were selected for each
      cut: occlusal, axial, and marginal. Statistical analysis was performed using two
      way ANOVA and Tukey HSD tests. RESULTS: For each replica, 6 measurements were
      made for the mesiodistal and the same for the buccolingual cuts, producing 12
      measurement points per crown (4 measurements for marginal, 4 for axial, 4 for
      occlusal), 120 measurements for each group (40 measurements for marginal, 40 for
      axial, 40 for occlusal), and 480 measurements in total. Two-way ANOVA revealed
      location to be a significant factor (p = 0.001). No significant differences among
      groups (p = 0.456), and no interactions between groups and locations (p = 0.221)
      were found. Means for the occlusal site were significantly larger than other
      sites in most group combinations, while the difference between the marginal and
      axial sites was not significant. No significant differences among groups were
      found for each measurement. The marginal gaps ranged from 125.46 +/- 25.39 MUm
      for group 3 to 135.59 +/- 24.07 MUm for group 4. The smallest axial mean was in
      group 1 (98.10 +/- 18.77 MUm), and the largest was 127.25 +/- 19.79 MUm in group
      4. The smallest occlusal mean was in group 2 (166.53 +/- 36.51 MUm), and the
      largest occlusal mean was in group 3 (203.32 +/- 80.24 MUm). CONCLUSIONS: Ceramic
      crowns, which were made using all-digital approach or cast digitization by a
      laboratory or intraoral scanner had comparable fit to those produced by
      conventional approach.

PMID- 30091169
TI  - Cardiovascular protection in type 2 diabetes: Insights from recent outcome
      trials.
AB  - This review examines recent randomized controlled cardiovascular (CV) outcome
      trials of glucose-lowering therapies in type 2 diabetes and their impact on the
      treatment of patients with type 2 diabetes. The trials were designed to comply
      with regulatory requirements to confirm that major adverse cardiac events (MACE)
      are not detrimentally affected by such therapies. Trials involving dipeptidyl
      peptidase-4 (DPP-4) inhibitors did not alter a composite MACE outcome comprising
      CV deaths, non-fatal myocardial infarction and non-fatal stroke; however, the
      possibility that some members of this class might incur a small increased risk or
      worsening of heart failure cannot be excluded. Some studies on glucagon-like
      peptide-1 receptor agonists (liraglutide: LEADER trial; semaglutide: SUSTAIN-6
      trial) found significant benefits for MACE, while treatment with sodium-glucose
      co-transporter-2 inhibitors (empagliflozin: EMPA-REG OUTCOME trial;
      canagliflozin: CANVAS trial) also significantly reduced MACE and reduced
      hospitalization for heart failure. Comparisons among trials are complicated by
      variance in the populations recruited, particularly CV status at randomization,
      and differences in trial design, data collection and analyses. A large proportion
      of patients recruited into these trials have previously experienced adverse CV
      events; thus, the therapies are mostly assessing secondary prevention of a
      further event. This contrasts with the overall type 2 diabetes population
      receiving glucose-lowering therapies, of whom the majority will not have had MACE
      and will be regarded as primary prevention. Overall, the trials provide
      reassuring evidence that new glucose-lowering medications do not adversely affect
      CV events and some of these agents may offer CV protection.

PMID- 30091170
TI  - Literature review of the adverse events associated with botulinum toxin injection
      for the masseter muscle hypertrophy.
AB  - BACKGROUND: Masseteric hypertrophy is a benign condition characterized by the
      enlargement of the masseter muscles. A square-shaped jawline due to masseter
      muscle prominence or hypertrophy is one of the general characteristics of the
      Asian face, making it a frequent target for esthetic treatment requests. While
      the application of botulinum toxin on the masseter muscle is an off-label use, it
      is very popular in Asian countries. However, comprehensive reviews of the
      complications associated with this procedure remain limited in scope. OBJECTIVES:
      The goal of this study is to help physicians achieve a comprehensive
      understanding of the complications associated with neuromodulator injection over
      the masseter muscle via a thorough literature review. METHODS: A literature
      search was performed on the PubMed/MEDLINE, Google Scholar, and Science Direct
      databases using the search terms botulinum toxin, masseter hypertrophy,
      masseteric hypertrophy, and/or masseter hyperplasia. Literature from January 1994
      to February 2018 was deemed to be allegeable for inclusion and analysis. All
      available prospective and retrospective studies, case series, case reports, and
      expert reviews were included, with an emphasis on types of complications,
      incidence rate, onset time, recovery time, and product used. Articles that do not
      mention side effects, complications, or adverse events were excluded. RESULTS:
      Thirty-six articles were found, covering type, incidence rate, and clinical
      course of the complications. These studies were summarized into tabular form for
      easy reference and comparison. CONCLUSION: Botulinum toxin masseter injections
      are commonly performed procedures with good results and safety profiles. The
      majority of complications appeared within 2-4 weeks of injection and disappeared
      within 12 weeks. Despite the temporary nature of these complications, they often
      decrease patient satisfaction and confidence, so physicians should familiarize
      themselves with the regional anatomy and injection safety zones.

PMID- 30091171
TI  - Mortality in heart failure with atrial fibrillation: Role of digoxin and
      diuretics.
AB  - BACKGROUND: The impact of atrial fibrillation (AF) on mortality of patients with
      heart failure (HF) has been established. Nevertheless, the effect of some factors
      in mortality, such as digoxin or diuretic use, remains controversial. This study
      aims at assessing mortality in community-dwelling patients with stable HF related
      to AF and determines the relation of these drugs with prognosis. MATERIALS AND
      METHODS: Community-based cohort study of HF patients diagnosed between January
      2010 and December 2014 attended at any one of the 279 primary healthcare centres
      of the Catalan Institute of Health (Spain). Follow-up ended on December 31, 2015,
      and the main outcome was mortality for all causes. The effect of clinical and
      demographic characteristics on survival was assessed by Cox proportional hazards
      model. RESULTS: A total of 13 334 HF patients were included. Mean age was 78.7
      years (SD 10.1), and 36.8% had AF. Mean follow-up was 26.9 months (SD 14.0). At
      the end of the study, 25.8% patients had died, and mortality was higher when AF
      was present (28.8% vs 24.1%, P < 0.001, respectively). Multivariate model
      confirmed the higher risk of death for AF patients (HR 1.10 95%, CI 1.02-1.19).
      Digoxin and diuretics were not associated with higher mortality in AF patients
      (HR 1.04 95% CI 0.92-1.18 and HR 1.04 95% CI 0.85-1.26, respectively).
      CONCLUSIONS: An excess of mortality in HF patients with AF was found in a large
      retrospective community-based cohort. Digoxin and diuretics did not affect
      mortality in HF patients with AF.

PMID- 30091172
TI  - Linagliptin as add-on to empagliflozin in a fixed-dose combination in Japanese
      patients with type 2 diabetes: Glycaemic efficacy and safety profile in a two
      part, randomized, placebo-controlled trial.
AB  - AIMS: This two-part, double-blind, double-dummy, randomized, placebo-controlled
      trial (83 sites) evaluated the efficacy and safety of empagliflozin (Empa) 10 or
      25 mg and linagliptin (Lina) 5 mg fixed-dose combinations (FDCs) in Japanese
      patients with type 2 diabetes mellitus (T2DM) who were poorly controlled with
      Empa. MATERIALS AND METHODS: Patients (previously drug-naive or using one oral
      antidiabetic drug for >= 12 weeks) entered an open-label stabilization period (16
      weeks, Empa 10 mg [Part A] or Empa 25 mg [Part B]). Subsequently, they received
      Empa 10 mg plus placebo (Plc) for Empa/Lina10/5 (Empa/Plc 10/5; Part A) or Empa
      25 mg plus Plc for Empa/Lina 25/5 (Empa/Plc 25/5; Part B) for 2 weeks. Patients
      with HbA1c 7.5-10.0% were randomized (1:1) to a 24-week regimen of once-daily
      Empa/Lina 10/5 (n = 107) or Empa/Plc 10/5 (n = 108) in Part A, or to Empa/Lina
      25/5 (n = 116) or Empa/Plc 25/5 (n = 116) in Part B, with a 28-week extension
      period in Part B. RESULTS: Change from baseline in HbA1c at Week 24 was greater
      (P < 0.0001) with Empa/Lina than with Empa/Plc (primary outcome, Empa/Lina 10/5: 
      0.94 vs -0.12%; adjusted mean difference, -0.82%; Empa/Lina 25/5: -0.91 vs 
      0.33%; adjusted mean difference, -0.59%). Over 24- and 52-week periods, higher
      proportions of patients achieved HbA1c < 7.0% and greater decreases in fasting
      plasma glucose were observed with Empa/Lina compared with Empa/Plc. Empa/Lina was
      well tolerated, with no unexpected adverse events or diabetic ketoacidosis. One
      case of confirmed hypoglycaemia with Empa/Plc 25/5 was reported. CONCLUSIONS:
      These results support Empa/Lina FDC as a potential option for Japanese patients
      with T2DM who require combination therapy. ClinicalTrials.gov NCT02489968.

PMID- 30091173
TI  - High-Performance Polymer Solar Cells Achieved by Introducing Side-Chain
      Heteroatom on Small-Molecule Electron Acceptor.
AB  - Side chains of photovoltaic materials play an important role in determining
      charge transport property, film morphology, and the corresponding device
      performance. In this work, two new acceptor materials, ATT-6 and ATT-7 with
      different side chains, m-hexylphenyl and m-hexyloxyphenyl on the
      indacenodithiophene, are designed and synthesized for applications in non
      fullerene polymer solar cells. ATT-7 shows a higher absorption coefficient,
      increased crystallinity, and improved electron mobility in comparison with ATT-6.
      Using wide-bandgap polymer poly[(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl)
      benzo[1,2-b:4,5-b']dithiophene))-alt-(5,5-(1',3'-di-2-thienyl-5',7'-bis(2
      ethylhexyl)benzo[1',2'-c:4',5'-c']dithiophene-4,8-dione)] (PBDB-T) as donor,
      optimized devices based on PBDB-T:ATT-7 and PBDB-T:ATT-6 delivers power
      conversion efficiencies of 10.30% and 8.39%, respectively. The higher performance
      of ATT-7-based device can be attributed to efficient exciton dissociation,
      reduced bimolecular recombination, and enhanced and balanced charge carrier
      mobilities. These results indicate that side-chain modification is an easy but
      efficient way in the design of high-performance non-fullerene acceptors.

PMID- 30091174
TI  - Identifying important species that amplify or mitigate the interactive effects of
      human impacts on marine food webs.
AB  - Some species may have a larger role than others in the transfer of complex
      effects of multiple human stressors, such as changes in biomass, through marine
      food webs. We devised a novel approach to identify such species. We constructed
      annual interaction-effect networks (IENs) of the simulated changes in biomass
      between species of the southeastern Australian marine system. Each annual IEN was
      composed of the species linked by either an additive (sum of the individual
      stressor response), synergistic (lower biomass compared with additive effects),
      or antagonistic (greater biomass compared with additive effects) response to the
      interaction effect of ocean warming, ocean acidification, and fisheries.
      Structurally, over the simulation period, the number of species and links in the
      synergistic IENs increased and the network structure became more stable. The
      stability of the antagonistic IENs decreased and became more vulnerable to the
      loss of species. In contrast, there was no change in the structural attributes of
      species linked by an additive response. Using indices common in food-web and
      network theory, we identified the species in each IEN for which a change in
      biomass from stressor effects would disproportionately affect the biomass of
      other species via direct and indirect local, intermediate, and global predator
      prey feeding interactions. Knowing the species that transfer the most synergistic
      or antagonistic responses in a food-web may inform conservation under increasing
      multiple-stressor impacts.

PMID- 30091175
TI  - The link between self-compassion and psychotic-like experiences: A matter of
      distress?
AB  - OBJECTIVES: Self-shaming and self-criticism have been shown to contribute to the
      emergence of distressing psychotic symptoms and psychotic-like experiences
      (PLEs). In contrast, a self-compassionate mindset may protect against negative
      evaluations in response to PLEs leading to less distress. This study explores the
      association between self-compassion, the frequency of PLEs, and their associated
      distress. DESIGN: The study used a correlational, cross-sectional design on a
      German community sample. METHODS: A total of 234 participants completed the self
      compassion scale (SCS), the Peters' Delusions Inventory, and a modified version
      of the Launay-Slade Hallucination Scale that measures frequency and distress of
      hallucinatory experiences. Pearson correlations between SCS and frequency of PLEs
      as well as between SCS and PLE-distress were compared. Additionally, network
      analyses of SCS and PLE-measures were calculated. RESULTS: Self-compassion was
      associated with less-frequent PLEs and with less PLE-distress, with stronger
      correlations between self-compassion and PLE-distress. The network analysis
      showed the self-compassion facets isolation and overidentification to be the
      closest links to PLE-distress. CONCLUSIONS: Self-compassion is associated with
      less PLE related distress. Prevention programmes and interventions that target
      the negative facets associated with lack of self-compassion may be promising.
      However, future studies need to explore the causal role of self-compassion facets
      in the formation of PLE-distress. PRACTITIONER POINTS: Low levels of self
      compassion are associated with being more distressed by psychotic experiences. As
      the self-compassion facets isolation and overidentification are most strongly
      related to distress, prevention and intervention programmes may benefit from
      focusing on these negative facets.

PMID- 30091176
TI  - Outcome of hospital outpatient treatment of functional gastrointestinal
      disorders.
AB  - BACKGROUND: Functional gastrointestinal disorders (FGIDs), are the commonest
      conditions observed in gastrointestinal (GI) practice, yet the outcomes of their
      outpatient care are not known. We evaluated the outcome for patients with FGIDs
      attending a specialist GI clinic. METHODS: Consecutive, newly referred patients
      with a FGID attending a specialist GI clinic in a tertiary hospital, over a one
      year period were reviewed and then completed a phone survey to assess current
      symptoms. RESULTS: Of 102 patients 57% had IBS, 28% functional dyspepsia (FD) and
      15% other functional disorders. At interview a median of 402 days after the last
      consultation 38% expressed symptom improvement, but 64% remained concerned about
      their condition despite 62% having been reassured. After treatment 50% of
      employed patients took time off work because of gut symptoms. FD patients were
      less likely to be symptomatically improved than other FGIDs (21% vs 45%, P=0.02).
      Patients given a low-FODMAP diet were more likely than others to achieve symptom
      improvement (53% vs 31%, P=0.03); PPI-treated patients were less likely to
      experience improvement (22% vs 44%, P=0.05); other treatments did not predict
      outcome. Number of visits, seniority of clinician, duration of care, and co
      morbidities did not predict outcome. CONCLUSIONS: One year after attending a
      specialist GI clinic a minority of patients with FGIDs were symptomatically
      improved. Failure to benefit by many patients may relate to the nature of
      patients and conditions being treated or the limited nature and range of
      treatments offered. Different models of care, including more diverse multi
      disciplinary models, should be explored. This article is protected by copyright.
      All rights reserved.

PMID- 30091177
TI  - Transporters in Drug Development: 2018 ITC Recommendations for Transporters of
      Emerging Clinical Importance.
AB  - This white paper provides updated International Transporter Consortium (ITC)
      recommendations on transporters that are important in drug development following
      the 3rd ITC workshop. New additions include prospective evaluation of organic
      cation transporter 1 (OCT1) and retrospective evaluation of organic anion
      transporting polypeptide (OATP)2B1 because of their important roles in drug
      absorption, disposition, and effects. For the first time, the ITC underscores the
      importance of transporters involved in drug-induced vitamin deficiency (THTR2)
      and those involved in the disposition of biomarkers of organ function (OAT2 and
      bile acid transporters).

PMID- 30091178
TI  - Enhanced Electroluminescence from Organic Light-Emitting Diodes with an Organic
      Inorganic Perovskite Host Layer.
AB  - The development of host materials with high performance is essential for
      fabrication of efficient and stable organic light-emitting diodes (OLEDs).
      Although host materials used in OLEDs are typically organics, in this study, it
      is shown that the organic-inorganic perovskite CH3 NH3 PbCl3 (MAPbCl3 ) can be
      used as a host layer for OLEDs. Vacuum-evaporated MAPbCl3 films have a wide band
      gap of about 3 eV and very high and relatively balanced hole and electron
      mobilities, which are suitable for the host material. Photoluminescence and
      electroluminescence take place through energy transfer from MAPbCl3 to an organic
      emitter in films. Incorporation of an MAPbCl3 host layer into OLEDs leads to a
      reduction of driving voltage and enhancement of external quantum efficiency as
      compared to devices with a conventional organic host layer. Additionally, OLEDs
      with an MAPbCl3 host layer demonstrate very good operational stability under
      continuous current operation. These results can be extensively applied to organic
      and perovskite-based optoelectronics.

PMID- 30091179
TI  - Feasibility and safety of arthroscopic medial glenohumeral ligament and
      subscapularis tendon repair with knotless anchors: A cadaveric study in dogs.
AB  - OBJECTIVE: To test the feasibility and safety of an arthroscopic imbrication of
      the medial glenohumeral ligament (MGHL) and the subscapularis tendon with
      knotless anchors in dogs. STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Ten
      limbs. METHODS: Cranial and caudal arms of the MGHL were imbricated with a 2.9-
      or a 2.4-mm knotless anchor. A horizontal mattress suture secured with a 3.5-mm
      knotless anchor was used to imbricate the subscapularis tendon. Computed
      tomography measurements included (1) the bone stock around the anchors, (2) the
      angle between the anchor and the joint surface (insertion angle), and (3) the
      angle formed by lines tangent to the cortices of the bones (safety angle). Limbs
      were dissected to assess the position of anchors. Safety and insertion angles and
      bone stock were compared among anchors with a Kruskal-Wallis test (P < .05).
      RESULTS: Surgical repairs were achieved in all limbs, with only 2 of 30 anchors
      incorrectly placed, both in the glenoid. The safety angle of the humeral anchor
      (HA; median, 89 degrees ) was greater than that of the cranial glenoid anchor
      (CrGA; P = .0017) and the caudal glenoid anchor (CdGA; P < .001). The insertion
      angle of the HA (median, 68 degrees ) was also greater than that of the other
      anchors (P < .001 and P = .001). The insertion angle of the CrGA (median, 26
      degrees ) was greater (P = .0191) than that of the CdGA (median, 7 degrees ). All
      anchors were inserted at the MGHL and subscapularis footprint. CONCLUSION:
      Arthroscopic imbrication of MGHL and subscapularis tendon was feasible. HA were
      safer to place than glenoid anchors. CLINICAL SIGNIFICANCE: The results of this
      feasibility study justify further evaluation of the indications and outcomes of
      this technique in dogs with shoulder instability.

PMID- 30091180
TI  - Radiological parameters related to success of the round window approach in
      cochlear implantation: A retrospective study.
AB  - OBJECTIVES: To evaluate the radiologic parameters related to success of round
      window (RW) approach for cochlear implantation (CI). DESIGN: A retrospective
      cohort study. SETTING: Academic-tertiary centre. PARTICIPANTS: Eighty-four
      consecutive patients without inner ear anomaly who underwent CI with the intent
      of the RW approach were included. The RW approach was performed through the
      facial recess after posterior tympanotomy (RW group). When the RW approach was
      not possible despite maximum effort to expose the RW, promontory cochleostomy
      (PC) was performed (PC group). MAIN OUTCOME MEASURES: The following radiologic
      parameters were compared between the two groups: (a) Width of the facial recess,
      (b) oblique distance between the cochlear basal turn (CBT) and facial nerve (FN),
      (c) anteroposterior distance between the posterior margin of the RW and FN and
      (d) angle between the EAC and CBT. RESULTS: Seventy patients (83.3%) were
      implanted using the RW approach, and 14 patients (16.7%) underwent the PC
      approach for CI. The anteroposterior distance between the posterior margin of the
      RW and FN and the angle between the EAC and CBT in the RW group were
      significantly longer and wider than those in the PC group (P < 0.001 and P =
      0.001, respectively). Multivariate analysis revealed that these two parameters
      were independent parameters for success of the RW approach. CONCLUSIONS: The
      distance between the posterior margin of the RW and FN and the angle between the
      EAC and CBT are associated with success of RW approach. Therefore, preoperative
      radiologic analysis of the two parameters might help CI surgeons to select RW
      approach.

PMID- 30091182
TI  - Regulation of mechanotransduction: Emerging roles for septins.
AB  - Cells exist in dynamic three-dimensional environments where they experience
      variable mechanical forces due to their interaction with the extracellular
      matrix, neighbouring cells and physical stresses. The ability to constantly and
      rapidly alter cellular behaviour in response to the mechanical environment is
      therefore crucial for cell viability, tissue development and homeostasis.
      Mechanotransduction is the process whereby cells translate mechanical inputs into
      biochemical signals. These signals in turn adjust cell morphology and cellular
      functions as diverse as proliferation, differentiation, migration and apoptosis.
      Here, we provide an overview of the current understanding of mechanotransduction
      and how septins may participate in it, drawing on their architecture and
      localization, their ability to directly bind and modify actomyosin networks and
      membranes, and their associations with the nuclear envelope.

PMID- 30091181
TI  - Ten-year changes of intraocular pressure in adults: the Liwan Eye Study.
AB  - IMPORTANCE: Understanding the longitudinal intraocular pressure (IOP) changes and
      potential risk factors in adults is important for future glaucoma control in the
      aging society. BACKGROUND: Limited longitudinal studies exist in Asia
      investigating the longitudinal IOP changes and with varying results. DESIGN:
      Population-based cohort study. PARTICIPANTS: 1405 baseline participants from the
      Liwan Eye Study. METHODS: All baseline participants were invited for the 10-year
      follow-up examination in 2013. IOP (by Tonopen), central corneal thickness (CCT;
      by ultrasound), refractive error (by autorefractor), blood pressure, height and
      weight were measured per standardized protocol and the presence of hypertension
      or diabetes was collected by questionnaire. Follow-up examinations were conducted
      using the same equipment with proper calibration. Linear regression analysis was
      used to assess the association between IOP change and potential risk factors.
      MAIN OUTCOME MEASURES: 10-year IOP change. RESULTS: Of the 791 participants at
      the 10-year follow-up, IOP data were available for 602 participants with a mean
      age of 60.9 years (55.5% female). The average IOP change over 10 years was an
      increase of 1.44 mmHg (95% confidence interval, 1.12-1.75). Linear regression
      showed that 10-year IOP change was not associated with baseline age, gender, body
      mass index (BMI), CCT, spherical equivalence (SE), hypertension or diabetes.
      However, it was positively associated with longitudinal increase of BMI when
      longitudinal changes of BMI and SE were included in the model (P < 0.001).
      CONCLUSIONS AND RELEVANCE: We observed a small increase in IOP over 10 years in
      this adult Chinese population, which was positively related to the longitudinal
      change in BMI.

PMID- 30091183
TI  - Avoiding anchoring bias by moving beyond 'mechanical falls' in geriatric
      emergency medicine.

PMID- 30091184
TI  - Unconventional RNA-binding proteins step into the virus-host battlefront.
AB  - The crucial participation of cellular RNA-binding proteins (RBPs) in virtually
      all steps of virus infection has been known for decades. However, most of the
      studies characterizing this phenomenon have focused on well-established RBPs
      harboring classical RNA-binding domains (RBDs). Recent proteome-wide approaches
      have greatly expanded the census of RBPs, discovering hundreds of proteins that
      interact with RNA through unconventional RBDs. These domains include protein
      protein interaction platforms, enzymatic cores, and intrinsically disordered
      regions. Here, we compared the experimentally determined census of RBPs to gene
      ontology terms and literature, finding that 472 proteins have previous links with
      viruses. We discuss what these proteins are and what their roles in infection
      might be. We also review some of the pioneering examples of unorthodox RBPs whose
      RNA-binding activity has been shown to be critical for virus infection. Finally,
      we highlight the potential of these proteins for host-based therapies against
      viruses. This article is categorized under: RNA Interactions with Proteins and
      Other Molecules > Protein-RNA Interactions: Functional Implications RNA in
      Disease and Development > RNA in Disease RNA Interactions with Proteins and Other
      Molecules > RNA-Protein Complexes.

PMID- 30091185
TI  - Long-Term Cognitive Prognosis of Profoundly Deaf Older Adults After Hearing
      Rehabilitation Using Cochlear Implants.
AB  - OBJECTIVES: To analyze long-term cognitive status and function after cochlear
      implantation in profoundly deaf individuals. DESIGN: Prospective observational
      longitudinal study. SETTING: Ten academic medical centers referent for cochlear
      implantation. PARTICIPANTS: Individuals aged 65 and older who qualified for
      cochlear implantation (N=70). MEASUREMENTS: Cognitive tests were administered
      before cochlear implantation and 1 and 5 or more years after cochlear
      implantation. Evaluation consisted of 6 tests assessing attention, memory,
      orientation, executive function, mental flexibility, and fluency. Cognitive
      status was determined as normal, mild cognitive impairment (MCI), or dementia.
      Speech perception in quiet and noisy conditions was assessed using disyllabic
      words, and quality of life was assessed using the Nijmegen Cochlear Implant
      Questionnaire. RESULTS: Mean follow-up was 6.8 years (range 5.5-8.5 years).
      Speech perception scores and quality of life remained stable from 1 to 7 years
      after cochlear implantation. Of 31 participants (45%) with MCI before cochlear
      implantation, 2 (6%) developed dementia during follow-up, 19 (61%) remained
      stable, and 10 (32%) returned to normal cognition. None of the 38 with normal
      cognition developed dementia during follow-up, although 12 (32%) developed MCI.
      CONCLUSION: MCI is highly prevalent in older adults with profound hearing loss.
      Nevertheless, we observed a low rate of progression to dementia, and cognitive
      function improved in some individuals with MCI at baseline. These results
      highlight that cochlear implantation should be strongly considered in profoundly
      deaf individuals, even those with MCI, who may have a specific subtype of MCI,
      with a possible positive effect of hearing rehabilitation on neurocognitive
      functioning.

PMID- 30091186
TI  - New piperidine derivative DTPEP acts as dual-acting anti-breast cancer agent by
      targeting ERalpha and downregulating PI3K/Akt-PKCalpha leading to caspase
      dependent apoptosis.
AB  - OBJECTIVES: In our ongoing studies to develop ER targeting agents, we screened
      for dual-acting molecules with a hypothesis that a single molecule can also
      target both ER positive and negative groups of breast cancer. MATERIALS AND
      METHODS: 1-(2-(4-(Dibenzo[b,f]thiepin-10-yl)phenoxy)ethyl)piperidine (DTPEP) was
      synthesized and screened in both MCF-7 (ER+ve) and MDA-MB-231 (ER-ve) cells.
      Assays for analysis of cell cycle, ROS, apoptosis and MMP loss were carried out
      using flow cytometry. Its target was investigated using western blot,
      transactivation assay and RT-PCR. In vivo efficacy of DTPEP was validated in LA-7
      syngeneic rat mammary tumour model. RESULTS: Here, we report identification of
      dual-acting molecule DTPEP that downregualtes PI3K/Akt and PKCalpha expression,
      induces ROS and ROS-dependent apoptosis, loss of mitochondrial membrane
      potential, induces expression of caspase indicative of both intrinsic and
      extrinsic apoptosis in MCF-7 and MDA-MB-231 cells. In MCF-7 cells, DTPEP
      downregulates ERalpha expression and activation. In MDA-MB-231 cells, primary
      cellular target of DTPEP is not clearly known, but it downregualtes PI3K/Akt and
      PKCalpha expression. In vivo study showed regression of LA-7 syngeneic mammary
      tumour in SD rat. CONCLUSIONS: We identified a new dual-acting anti-breast cancer
      molecules as a proof of concept which is capable of targeting both ER-positive
      and ER-negative breast cancer.

PMID- 30091187
TI  - Hospital readmission rates are similar between patients with mechanical versus
      bioprosthetic aortic valves.
AB  - BACKGROUND: The aim of this study was to evaluate hospital readmission rates and
      clinical outcomes between bioprosthetic (bAVR) and mechanical (mAVR) aortic valve
      replacements (AVR). METHODS: Adults aged 50 years or older undergoing isolated or
      concomitant AVR between 2011 and 2017 were included. The primary outcome was 5
      year hospital readmission. Multivariable logistic regression analysis was used to
      evaluate the risk-adjusted impact of bAVR versus mAVR on outcomes. RESULTS: A
      total of 2981 patients were included: 406 (14%) mAVR and 2575 (86%) bAVR. Mean
      follow-up was 2.9 +/- 1.9 years. Operative mortality was comparable (4% bAVR vs
      3% mAVR; P = 0.30). There was no risk-adjusted difference in 30-day (hazard ratio
      [HR] 1.32, P = 0.46), 1-year (HR 1.17, P = 0.52), or 5-year mortality (HR 0.99, P
      = 0.93). Aortic valve 5-year reoperation rates were comparable (1%, P = 0.32).
      Risk-adjusted hospital readmissions were similar at 30 days (14% vs 15%; P =
      0.63), 1 year (30% vs 27%; P = 0.43), and 5 years (55% vs 53%; P = 0.83) in the
      bAVR and mAVR groups, respectively. Similar findings were demonstrated when
      evaluating readmissions for bleeding (5-year readmission: 8% bAVR vs 10% mAVR; P
      = 0.36). CONCLUSIONS: In this analysis of over 2900 AVRs, readmissions within 5
      years were comparable between groups at approximately 50%, with patients being at
      highest risk in the early postdischarge period. Readmissions for bleeding
      constituted a minority of all readmissions for both cohorts.

PMID- 30091189
TI  - Performance characteristics and quality assurance considerations for displays
      used in interventional radiology and cardiac catheterization facilities.
AB  - PURPOSE: While the performance of displays used for the acquisition and primary
      interpretation of medical images has been well-characterized, notably absent are
      publications evaluating and discussing the performance of displays used in
      Interventional Radiology (IR) suites and Cardiac Catheterization (CC)
      laboratories. The purpose of this work was to evaluate the performance of these
      displays and to consider the challenges in implementation of display quality
      assurance practices in this environment. METHODS: Ten large format displays used
      in IR and CC suites were evaluated. A visual inspection of available test
      patterns was performed followed by a quantitative evaluation of several
      performance characteristics including luminance ratio, luminance response
      function, and luminance uniformity. Additionally, the local ambient lighting
      conditions were evaluated. RESULTS: Luminance ratios ranged from 243.0 to 1182.1
      with a mean value of 500.1 +/- 289.2. The maximum deviation between the luminance
      response function and the DICOM Grayscale Standard Display Function ranged from
      11.2% to 38.3% with a mean value of 26.2% +/- 10.9%. When evaluating luminance
      uniformity, the mean maximum luminance deviation was 13.2% +/- 3.5%. The mean
      value of luminance deviation from the median was 7.8% +/- 1.0%. Measured values
      of background illuminance ranged from 29.1 to 310.0 lux with a mean value of
      107.6 lux +/- 80.4 lux. While no mura or bad pixels were observed during visual
      inspection, damage including scrapes and scratches as well as smudges was common
      to most of the displays. CONCLUSION: This work provides much needed data for the
      characterization of the performance of the large format displays used in IR and
      CC laboratory suites. These data may be used as a point of comparison when
      implementing a display QA program.

PMID- 30091188
TI  - Trisenox induces cytotoxicity through phosphorylation of mitogen-activated
      protein kinase molecules in acute leukemia cells.
AB  - Trisenox (TX) has been used successfully for the treatment of acute promyelocytic
      leukemia (APL) patients. TX-induced cytotoxicity in APL cells remains poorly
      understood. In this study, we investigated the molecular mechanism of TX
      cytotoxicity using APL cell lines. We assessed TX toxicity by quantitatively
      measuring lactate dehydrogenase levels. Inhibition of cell cycle progression was
      assessed by confocal microscopy of Ki-67 expression. Apoptosis was evaluated by
      Western blot analysis of apoptotic proteins expression, immunocytochemistry, and
      confocal imaging of annexin V and propidium iodide. Mitogen-activated protein
      kinase (MAPK) signaling cascade was analyzed by Western blot analysis and
      inhibitor-based experiments with APL cells. We found that TX-induced cytotoxicity
      inhibited APL cell cycle progression. TX also induced significant (P < 0.05)
      changes in the expression levels of apoptotic molecules and activated the
      phosphorylation of MAPK signaling pathways in APL cells. Understanding the
      mechanism of TX cytotoxicity would be helpful in the design of new APL drugs.

PMID- 30091190
TI  - Porcine circovirus 3 is highly prevalent in serum and tissues and may
      persistently infect wild boar (Sus scrofa scrofa).
AB  - Porcine circovirus 3 (PCV-3) prevalence has been minimally investigated in wild
      boar; dynamics of infection and viral tissue distribution are currently unknown.
      In this study, serum samples from 518 wild boar (from years 2004 to 2018) were
      used to study frequency of infection. Also, serum samples from 19 boar captured
      and recaptured at least two times for a period of time from 1 month to 1 year
      were collected to determine PCV-3 infection dynamics. Finally, to elucidate PCV-3
      DNA organic distribution, sera, different tissues and faeces were obtained from
      35 additional wild boar. PCV-3 DNA was extracted and amplified with a
      conventional PCR. For the PCV-3 PCR-positive sera from the longitudinally sampled
      and different tissue types, a quantitative PCR was performed. Genome sequence was
      obtained from a number of PCV-3 PCR-positive samples from different years,
      different time-points of infection and tissues. Obtained results confirmed the
      susceptibility of wild boar to the virus, showing high frequency of PCV-3
      detection (221 out of 518, 42.66%) and demonstrating circulation at least since
      2004. Compiled data indicate the possibility of long-term infections, since 5 out
      of 10 PCV-3 PCR-positive boars longitudinally sampled showed positivity in
      samplings separated for more than 5 months. All tested tissue types' harboured
      PCV-3 genome, with the highest percentage of PCR positivity in submandibular
      lymph node, tonsil, lung, liver, spleen and kidney. The amount of DNA in all
      tested PCV-3 PCR-positive samples was moderate to low. All partial and complete
      PCV-3 sequences obtained from wild boar displayed high nucleotide identity,
      higher than 98%. In conclusion, this study further confirms that wild boar is
      susceptible to PCV-3 infection, showing high frequency of detection in this
      animal species. Furthermore, PCV-3 can be found in different tissues of wild boar
      and is apparently able to cause persistent infection.

PMID- 30091191
TI  - Background levels of micro-organisms in the busy urban environment of transport
      hubs.
AB  - AIMS: We constantly interact with our surrounding microbiome, including the micro
      organisms present in highly populated public places. However, data on everyday
      exposure to background levels of micro-organisms are limited. To address this,
      bacteria and fungi were collected and enumerated in settled dust from railway
      stations. METHODS AND RESULTS: Samples were collected weekly for 52 weeks, from
      up to three pre-determined surfaces in each of 17 railway stations in England and
      Scotland. Trained staff at each station took surface wipes, sending them to the
      laboratory for culture-based analysis for total bacteria and fungi. Maximum
      yields of bacteria at the stations were 107 -108 colony forming units (CFU) per
      cm2 , and 104 -105 CFU per cm2 for fungi. CONCLUSIONS: There was evidence of
      seasonal trends, with bacterial numbers rising from spring through to winter,
      while fungal numbers peaked in autumn. Microbial numbers were similar in samples
      taken at the same time at a given station. Influences on contamination levels
      were likely to be a combination of passenger numbers and station layout, with
      dust generated from construction work also contributing. SIGNIFICANCE AND IMPACT
      OF THE STUDY: A baseline of typical human exposure to micro-organisms in public
      transport hubs was established through the generation of a comprehensive
      database.

PMID- 30091192
TI  - Association of breastfeeding and malocclusion in 5-year-old children: Multilevel
      approach.
AB  - BACKGROUND: Breastfeeding plays an important role in child health, including the
      development of normal dental occlusion, but large epidemiological findings on the
      association breastfeeding-malocclusion are lacking. AIM: To investigate the
      association between the proportion of breastfed children in the city level and
      the prevalence of malocclusion in the primary dentition at age 5. DESIGN: This
      cross-sectional analysis used data from national population surveys on oral
      health and on breastfeeding practices. Data refer to 5278 5-year-old children and
      44 Brazilian towns. Information on malocclusion and individual sociodemographic
      characteristics were obtained from the 2010 Brazilian Oral Health Survey.
      Breastfeeding rates during the first year of life were extracted from the
      Breastfeeding Prevalence Survey in Brazilian Towns. Population sociodemographic
      data were analysed as confounder. Multilevel Poisson analyses were performed.
      RESULTS: Malocclusion prevalence was 63.3%. Towns exhibiting higher prevalence of
      breastfeeding among 9- to 12-month-olds presented lower prevalence of
      malocclusion among children at age 5 (PR 0.98; 95% CI 0.98-0.99). CONCLUSIONS:
      Lower prevalence of malocclusion among 5-year-old children was associated with a
      higher proportion of children breastfed at ages 9 to 12 months at a city level,
      regardless of sociodemographic factors. These findings highlight the importance
      of encouraging breastfeeding during a child's first year.

PMID- 30091193
TI  - Organic Mechanoluminescence with Aggregation-Induced Emission.
AB  - Mechanoluminescence (ML) involves the emission of light from various organic and
      inorganic materials upon mechanical stimulus. In this review, we contemplate the
      advances of metal-free, purely organic ML compounds with aggregation-induced
      emission (AIE), which give strong emission upon mechanical force. We show the new
      ML-AIE based materials can be used explore the basic of ML properties with
      structure-property relationships and molecular interactions. The flourishing idea
      of ML-AIE may help to find the characteristic and elusive component of ML as it
      partners with AIE, which upgrades the emission property in solids or aggregates.
      Recent advances in ML-AIE information could increase the wide scope of research
      in this expanding area, as these materials have promising applications in
      different optoelectronic areas.

PMID- 30091194
TI  - Missed opportunities for earlier diagnosis of Human Immunodeficiency Virus
      infection among adults presenting to Auckland District Health Board hospital
      services.
AB  - BACKGROUND: Earlier diagnosis of HIV infection improves health outcomes and
      reduces transmission. In New Zealand half of new HIV diagnoses between 2005 and
      2010 had a CD4 count below 350 cells/mm3 . HIV screening is already offered in
      antenatal settings in New Zealand, but not universally in hospital settings.
      AIMS: To assess the impact of missed opportunities to diagnose HIV infection in
      adults presenting to hospital services at Auckland District Health Board (ADHB).
      METHODS: Retrospective cohort analysis of all new diagnoses of HIV infection in
      adults aged 15-64 years residing within the ADHB catchment area over a seven-year
      period. Those who had contact with hospital services prior to diagnosis, but
      within their estimated window of undiagnosed infection, were compared to those
      without such contact. RESULTS: Of 201 newly diagnosed patients, 68 had prior
      hospital contact within their estimated window of HIV infection, 68% of whom were
      men who have sex with men. These patients could potentially have been diagnosed
      earlier by a median of 12 months (range 1-84). Missed opportunity visits occurred
      across a wide range of hospital services, and included visits for conditions that
      indicated risk for, or actual, HIV infection. Thirteen patients had HIV
      associated illnesses at the time of diagnosis that could have been prevented if
      diagnosed earlier. CONCLUSIONS: Our current risk-based HIV screening strategy
      commonly results in late diagnosis, negative health impacts and possibly
      avoidable transmissions. Further study is warranted to model the feasibility and
      potential impact of universal HIV screening at ADHB. This article is protected by
      copyright. All rights reserved.

PMID- 30091195
TI  - Response to Bell et al., 'The effect of increasing body mass index on
      laparoscopic surgery for colon and rectal cancer'.

PMID- 30091196
TI  - Inpatient palliative care of people dying in NSW hospitals or soon after
      discharge.
AB  - BACKGROUND: Palliative care can benefit all patients with life limiting diseases.
      AIMS: Describe hospital use in the final year of life, timing of palliative care,
      and variations by age and disease for patients receiving inpatient palliative
      care. METHODS: Retrospective cohort study of all New South Wales residents aged
      50 years and older who died (decedents) between July 2010 and June 2015 in
      hospital or within 30 days of discharge. Care type and diagnosis codes identified
      decedents who received inpatient palliative care. RESULTS: Of 150,770 decedents,
      34.4% received palliative care, a median of 10 days before death. Decedents were
      more likely to receive palliative care if they had cancer (64.7% v 13.3% for
      those without chronic conditions) or were younger (46.3% v. 25.0% of the oldest
      decedents). In their last year of life palliated decedents, on average, had three
      emergency department presentations and four hospital admissions - one involving
      surgery and one where palliation was the intent of care. Of the 30.1 days spent
      in hospital, 8.7 days involved palliative care. Older age and non-cancer
      diagnoses were associated with fewer days of inpatient palliation and shorter
      time between first palliative admission and death. Decedents dying out of
      hospital started palliative care 18 days earlier than those dying in hospital.
      CONCLUSION: Most decedents did not receive palliative care during hospital
      admission, and then only very late in life, limiting its benefits. Improved
      recognition of palliative need, including earlier identification, regardless of
      age and disease, will enhance the quality of care for the dying. This article is
      protected by copyright. All rights reserved.

PMID- 30091197
TI  - A Matter of Life and Death: Integrating Mattering into the Interpersonal
      Psychological Theory of Suicide.
AB  - OBJECTIVE: This paper advocates for a more robust sense of mattering into the
      interpersonal-psychological theory of suicide (IPTS) constructs of perceived
      burdensomeness and thwarted belongingness. According to IPTS, suicide is
      precipitated in part by the presence of these twin constructs. IPTS theorists
      rely on mattering, or feeling significant to others, to undergird theoretical
      constructs. This is not surprising, as mattering theorists herald "significance
      to others" as essential to one's will to live. However, IPTS theorists solely
      leverage mattering to explain perceived burdensomeness. METHOD: This paper
      summarizes the existing suicide literature on IPTS and mattering. Further, this
      paper extensively reviews how mattering has been incorporated into IPTS to date,
      and possibilities for how mattering could be more fully integrated into the
      theory. RESULTS: IPTS theorists rely on select mattering elements to define
      perceived burdensomeness. Strong theoretical overlap exists between mattering and
      thwarted belongingness. CONCLUSION: Mattering can play central role in
      understanding both perceived burdensomeness and thwarted belongingness.
      Implications for future research and use of mattering-enriched IPTS are
      discussed.

PMID- 30091198
TI  - Salivary proteins and peptides in the aetiology of caries in children: Systematic
      literature review.
AB  - BACKGROUND: To assess the relationship of chosen salivary proteins and peptides
      levels with the occurrence of caries in children. METHODS: PubMed, MEDLINE and
      EMBASE databases from 2000 to 2018 were researched for original observational
      studies published in English. The risk of bias and quality of the included papers
      were assessed regarding the guidelines by Fowkes and Fulton. RESULTS: Twenty-two
      studies were included in the review, from which the issue of glycoproteins
      (including immunoglobulins), AMPs and salivary enzymes was discussed. The
      research involved primary dentition (13 papers), as well as mixed (7) and
      permanent dentition (5). Caries assessment included visual inspection, dmft/s and
      DMFT/S indexed; quantity of Streptococcus mutans and Lactobacillus spp. bacteria;
      and caries risk assessment. DISCUSSION: The results of studies regarding the
      connection between salivary peptides and proteins and caries development in
      children are promising; however, further investigations should be undertaken. The
      majority of studies included are case-control and cross-sectional; however, it is
      necessary to conduct more cohort studies with adequate follow-up prior to
      considering this as markers for caries risk assessment.

PMID- 30091199
TI  - The use of an esophageal catheter to check the results of left atrial posterior
      wall isolation in the treatment of atrial fibrillation.
AB  - BACKGROUND: Left atrial posterior wall isolation (LAPWI) via catheter, surgical,
      and hybrid techniques is a promising treatment for persistent atrial fibrillation
      (PersAF). We investigated whether confirmation of LAPWI can be achieved using an
      esophageal pacing and recording electrode. METHODS: Patients undergoing PersAF
      ablation with the intention to achieve LAPWI were enrolled. Two approaches to
      LAPWI were tested: (1) ablation using endocardial catheter ablation only, and (2)
      "Staged Hybrid" ablation with thoracoscopic epicardial ablation, followed by
      endocardial left atrial electrophysiological study and catheter ablation where
      necessary. Patients enrolled in the study all required further catheter ablation
      to achieve LAPWI in this group. In both the groups, esophageal recording and
      esophageal pacing was performed at the start of mapping and electrophysiological
      study and compared with endocardial electrophysiological findings. This was
      repeated at the end of the procedure. RESULTS: Twenty patients (16 M, four F)
      were studied. Endocardial electrophysiological study showed that in none of the
      cases was the posterior left atrial wall electrically isolated at the start of
      the study. One patient with Barrett's esophagus failed to sense or pace from the
      esophagus at any point in the study. In the remaining 19/19, esophageal pacing
      captured the atrial rhythm at the start of the procedure. LAPWI was then achieved
      in 17/19 using endocardial catheter ablation; retesting at this point showed
      sensing and capture of the atrium from the esophagus was abolished. In the
      remainder sensing and capture persisted. CONCLUSIONS: Esophageal pacing can be
      used to confirm or refute electrical isolation of the left atrial posterior wall.

PMID- 30091200
TI  - Starfish larvae lose substantial energy to maintain digestion under ocean
      acidification conditions.

PMID- 30091201
TI  - Cultural adaptations and therapist multicultural competence: Two meta-analytic
      reviews.
AB  - Mental health treatments can be more effective when they align with the culture
      of the client and when therapists demonstrate multicultural competence. We
      summarize relevant research findings in two meta-analyses. In the meta-analysis
      examining culturally adapted interventions, the average effect size across 99
      studies was d = 0.50 (0.35 after accounting for publication bias). In the second
      meta-analysis on 15 studies of therapist cultural competence, the results
      differed by rating source: Client-rated measures of therapist cultural competence
      correlated strongly (r = 0.38) with treatment outcomes but therapists' self-rated
      competency did not (r = 0.06). We describe patient considerations and research
      limitations. We conclude with research supported therapeutic practices that help
      clients benefit from modifications to treatment related to culture.

PMID- 30091202
TI  - Why Do B-P and Al-P Polymers Differ? Structures, Stability, and Electronic
      Properties of Chain and Ring [H2 PEH2 ]n Oligomers (E=B, Al; n=1-15).
AB  - Chain and ring [H2 PEH2 ]n oligomers (E=B, Al; n=2-15) have been computationally
      studied at the B3LYP/def2-TZVP level of theory. A strong tendency to cyclization
      was found for the chain Al-P oligomers with n>7, whereas analogous long B-P
      oligomers can exist as chain structures. Subsequent oligomerization enthalpies
      approach each other very closely for the ring and chain oligomers with an
      increase of n. However, these oligomers have very different electronic properties
      with band gaps below 0.2 eV for the chain [H2 PBH2 ]15 and more than 5 eV for the
      ring isomer [H2 PEH2 ]15 . The molecular orbitals in the ring oligomers are
      highly delocalized, whereas for the chain isomers, the HOMO and LUMO are
      localized at the different ends of the oligomeric chain.

PMID- 30091203
TI  - Melatonin and 5-fluorouracil co-suppress colon cancer stem cells by regulating
      cellular prion protein-Oct4 axis.
AB  - Melatonin suppresses tumor development. However, the exact relationship between
      melatonin and cancer stem cells (CSCs) is poorly understood. This study found
      that melatonin inhibits colon CSCs by regulating the PrPC -Oct4 axis. In
      specimens from patients with colorectal cancer, the expressions of cellular prion
      protein (PrPC ) and Oct4 were significantly correlated with metastasis and tumor
      stages. Co-treatment with 5-fluorouracil (5-FU) and melatonin inhibited the stem
      cell markers Oct4, Nanog, Sox2, and ALDH1A1 by downregulating PrPC . In this way,
      tumor growth, proliferation, and tumor-mediated angiogenesis were suppressed. In
      colorectal CSCs, PRNP overexpression protects Oct4 against inhibition by 5-FU and
      melatonin. In contrast, Nanog, Sox2, and ALDH1A1 have no such protection. These
      results indicate that PrPC directly regulates Oct4, whereas it indirectly
      regulates Nanog, Sox2, and ALDH1A1. Taken together, our findings suggest that co
      treatment with anticancer drug and melatonin is a potential therapy for
      colorectal cancer. Furthermore, PrPC maintains cancer stemness during tumor
      progression. Therefore, targeting the PrPC -Oct4 axis may prove instrumental in
      colorectal cancer therapy.

PMID- 30091204
TI  - Cannabinoid-1 receptor regulates mitochondrial dynamics and function in renal
      proximal tubular cells.
AB  - AIMS: To evaluate the specific role of the endocannabinoid/cannabinoid type-1
      (CB1 R) system in modulating mitochondrial dynamics in the metabolically active
      renal proximal tubular cells (RPTCs). MATERIALS AND METHODS: We utilized
      mitochondrially-targeted GFP in live cells (wild-type and null for the CB1 R) and
      electron microscopy in kidney sections of RPTC-CB1 R-/- mice and their littermate
      controls. In both in vitro and in vivo conditions, we assessed the ability of CB1
      R agonism or fatty acid flux to modulate mitochondrial architecture and function.
      RESULTS: Direct stimulation of CB1 R resulted in mitochondrial fragmentation in
      RPTCs. This process was mediated, at least in part, by modulating the
      phosphorylation levels of the canonical fission protein dynamin-related protein 1
      on both S637 and S616 residues. CB1 R-induced mitochondrial fission was
      associated with mitochondrial dysfunction, as documented by reduced oxygen
      consumption and ATP production, increased reactive oxygen species and cellular
      lactate levels, as well as a decline in mitochondrial biogenesis. Likewise, we
      documented that exposure of RPTCs to a fatty acid flux induced CB1 R-dependent
      mitochondrial fission, lipotoxicity and cellular dysfunction. CONCLUSIONS: CB1 R
      plays a key role in inducing mitochondrial fragmentation in RPTCs, leading to a
      decline in the organelle's function and contributing to the renal tubular injury
      associated with lipotoxicity and other metabolic diseases.

PMID- 30091205
TI  - Determinants of outcomes following outpatient placement of implantable
      cardioverter defibrillators in a Medicare Advantage population.
AB  - BACKGROUND: Recipients of ICD are likely to have several risk factors that could
      interfere with successful use of implantable cardioverter defibrillators (ICDs).
      HYPOTHESIS: Age, sex, and factors indicated in claims are associated with one
      year mortality and complications after ICD placement. METHODS: Adult Medicare
      Advantage patients who underwent outpatient ICD implantation from January 2014 to
      September 2015 were included. Age, sex, Charlson Comorbidity Index (CCI), prior
      year hospitalization and emergency department (ED) visit, diabetes, heart
      failure, ischemic heart disease, and indicators of the need for pacing were
      evaluated as risk factors. Mortality and device-related complications (lead and
      nonlead) were assessed at one-year post-procedure using Kaplan-Meier and Cox
      Proportional Hazard analysis. RESULTS: Among 8450 patients who underwent
      implantation, 1-year event-free survival was 80.1%, based on an overall composite
      measure of complications and mortality. Adjusted survival analysis showed that
      age >= 65, male sex, incremental increase in CCI, heart failure, prior year
      hospitalization, ED visit, and prior year pacing procedure were significant
      predictors of mortality. Age >= 65, male sex, and prior year hospitalization were
      significant predictors of a composite measure of device-related complications.
      CCI and prior hospitalization were significant predictors of a composite measure
      of any adverse outcome. CONCLUSIONS: Results suggest most patients in an older
      population do not experience adverse outcomes in the year following ICD
      implantation. The risk of mortality may be greater in men, patients over the age
      of 65, and patients with greater general morbidity, heart failure, or a history
      of a pacing procedure.

PMID- 30091206
TI  - "Coaching and Peer-Assisted Learning" (C-PAL) - The mental health nursing student
      experience: A qualitative evaluation.
AB  - : WHAT IS KNOWN ON THE SUBJECT?: There is increasing demand for clinical
      placements for pre-registration nursing students. New models of mentorship have
      been developed to meet the demand for clinical placements by increasing the
      number of students within each placement. At present there are no published
      research studies into the effectiveness of team mentorship utilized by pre
      registration nursing students within in-patient mental health settings. WHAT DOES
      THIS PAPER ADD TO EXISTING KNOWLEDGE?: This paper reports findings from a study
      that explored the experiences of mental health students within the social world
      of their clinical placement, adopting a new approach to practice learning where
      students support each other's learning. Students found their engagement in the
      pilot project as valuable as being exposed to the new team mentorship model which
      introduced them to peer-assisted learning. The learning that arose from peer
      assisted learning within team mentorship appeared to provide learning
      opportunities that enabled students' to develop greater self-awareness and
      confidence. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: Peer-assisted learning where
      students support the learning of each other, can lead to a wider range of
      learning opportunities for, as well as between, nursing students. In order for
      students to participate in care and become a "learning team," suitable in-patient
      mental health wards need to be identified that can support this new approach to
      the supervision, assessment and support of students. The establishment of team
      mentorship within mental health in-patient settings is dependent on the support
      provided by practice educators and university link lecturers to nurse mentors and
      coaches which in turn, determines the quality of the student experience.
      ABSTRACT: Introduction This paper presents findings from a study that evaluated
      mental health nursing students' experience of a team mentoring model called
      Coaching and peer-assisted learning (C-PAL). At present there are no published
      research studies into the effectiveness of team mentorship utilized by nursing
      students within in-patient mental health settings. Aim The study utilized an
      interpretivist methodology where the focus was on individuals in their social
      world. Method Two focus groups were held with fifteen students who had
      experienced C-PAL in four in-patient wards. Findings Students' overall experience
      of piloting C-PAL was positive. Learning opportunities (Theme 3) appeared to be
      dependent on the quality of peer support (Theme 5) which in turn, enhanced the
      learner experience and increased the level of student confidence (Theme 6). Less
      positive experiences included inadequate preparation (Theme 1), poor
      understanding of the model and competition for learning experiences. Implications
      for practice We tentatively suggest that team mentorship models such as C-PAL may
      be suitable for acute in-patient mental health settings. The success of C-PAL
      depends upon the preparation of nursing staff, mentors (Theme 4), coaches and
      students in relation to role expectations, shift rostering (Theme 2) and the
      implementation of "huddling" to promote opportunistic learning.

PMID- 30091207
TI  - Sequential facial skin rejuvenation with intense pulsed light and non-ablative
      fractionated laser resurfacing in fitzpatrick skin type II-IV patients: A
      prospective multicenter analysis.
AB  - BACKGROUND: While skin aging is triggered by multiple factors and typically
      presents with multiple manifestations, conventional treatment regimens deploy a
      single treatment modality. Typical approaches exploit ablative techniques, which
      involve considerable patient discomfort and downtime and can induce adverse
      events. Non-ablative fractionated laser (NAFL) resurfacing promotes
      neocollagenesis, with significantly fewer complications and discomfort. At the
      same time, intense pulsed light (IPL) therapies have a marked impact on skin
      tone, with an effect on collagen deposition. This study evaluated the combined
      effect of same-day, sequential IPL-NAFL treatment on photoaging of the face.
      DESIGN: In this prospective study, 30 patients presenting Fitzpatrick skin types
      II-IV, elastosis scores 3-6 and mild to moderate pigmentation, underwent three
      sessions, of full-face IPL therapy, followed immediately by NAFL treatment,
      conducted at 4-6 weeks intervals. Wrinkle/elastosis and skin qualities were
      scored at 1, 3, and 6 months after the last treatment session. Immediate
      responses were evaluated up to 30 min following treatment and adverse events were
      monitored throughout the study period. RESULTS: Wrinkle/elastosis scores
      gradually improved over the treatment period, with 59% of patients presenting a
      >=1-point improvement in FES scores by the 1-month follow-up session, which
      persisted also at the 6 months follow-up visit. Good to excellent pigmentation
      responses were recorded for >=63% and improvements in texture, brightness, and
      tightness were recorded for >=80% of patients throughout the follow-up period.
      Over 90% of the treated patients exhibited improved or much improved overall
      appearance. Patient scorings and satisfaction level reflected physician
      assessments. Treatments were well tolerated and the social downtime observed was
      of 1.5 +/- 0.25 days. CONCLUSION: The same-day combined IPL-NAFL regimen proved
      safe and elicited a significant skin rejuvenating effect, in a similar manner to
      that shown in other same-day combined therapies, without prolonging downtime of
      each individual modality. Lasers Surg. Med. (c) 2018 The Authors. Lasers in
      Surgery and Medicine Published by Wiley Periodicals, Inc.

PMID- 30091209
TI  - Adherence to the Healthy Nordic Food Index and the incidence of acute myocardial
      infarction and mortality among patients with stable angina pectoris.
AB  - BACKGROUND: The Healthy Nordic Food Index (HNFI) has been associated with
      beneficial effects on markers of cardiovascular disease (CVD). Whether such
      effects are present among patients with established coronary heart disease is
      unknown. In the present study, we investigated the association between adherence
      to the HNFI and the risk of acute myocardial infarction (AMI) (fatal or nonfatal)
      and death among patients with stable angina pectoris. METHODS: In the Western
      Norway B-vitamin Intervention Trial, participants completed a 169-item semi
      quantitative food frequency questionnaire. The HNFI was calculated from six food
      groups (fish, cabbage, apples/pears, root vegetables, whole grain bread and
      oatmeal), scoring 0-6. Three adherence groups were defined: 0-1 points (low), 2-3
      points (medium) or 4-6 points (high). Cox regression analyses investigated
      associations between adherence to the HNFI and outcomes. RESULTS: Among 2019 men
      (79.7%) and women with mean age of 61.7 years, 307 patients experienced an AMI
      event during a median (25th and 75th percentiles) follow-up of 7.5 (6.3 and 8.7)
      years. Median follow-up for total mortality was 10.5 (9.3 and 11.7) years; 171
      patients died from CVD and 380 from any cause. No association between HNFI and
      the risk of AMI was detected. However, the HNFI was associated with a reduced
      risk of all-cause death, both by linear estimates [hazard ratio (95% confidence
      interval = 0.91 (0.84-0.98)] and by comparison of the highest with the lowest
      adherence group [hazard ratio (95% confidence interval = 0.70 (0.52-0.95)].
      CONCLUSIONS: The results of the present study suggest that a Healthy Nordic diet
      may reduce mortality in patients with established CVD.

PMID- 30091208
TI  - Involvement of Akt in mitomycin C and its analog triggered cytotoxicity in MCF-7
      and K562 cancer cells.
AB  - Mitomycin C (MC) is a well-known DNA alkylating agent. MC analog, 10-decarbamoyl
      mitomycin C (DMC), unlike MC, has stronger effects on cancer with p53 mutation.
      We previously demonstrated that MC/DMC could activate p21WAF 1/ CIP 1 in MCF-7
      (p53-proficient) and K562 (p53-deficient) cells in a p53-independent mode. This
      study aimed to elucidate the upstream signaling pathway of p21WAF 1/ CIP 1
      activation triggered by MC/DMC. Besides p53, Akt plays an important role on
      deactivating p21WAF 1/ CIP 1 . The results showed that MC/DMC inhibited Akt in
      MCF-7 cells, but not in K562 cells. By knocking down p53, the Akt inhibition in
      MCF-7 cells was alleviated. This implied that the deactivated Akt caused by
      MC/DMC was p53-dependent. With Akt activator (SC79), p21WAF 1/ CIP 1 activation
      triggered by MC/DMC in MCF-7 cells was not reduced. This indicated that Akt
      inhibition triggered by MC/DMC was not associated with MC/DMC-induced p21WAF 1/
      CIP 1 activation. Label-free quantitative proteomic profiling analysis revealed
      that DMC has a stronger effect on down-regulating the PI3K/Akt signaling pathway
      in MCF-7 cells as compared to MC. No significant effect of MC/DMC on PI3K/Akt in
      K562 cells was observed. In summary, MC/DMC regulate Akt activation in a p53
      dependent manner. This Akt deactivation is not associated with p21WAF 1/ CIP 1
      activation in response to MC/DMC.

PMID- 30091210
TI  - Melatonin modulates autophagy and inflammation protecting human placental
      trophoblast from hypoxia/reoxygenation.
AB  - Melatonin has been proposed as a possible treatment for the deleterious effects
      of hypoxia/reoxygenation (H/R), such as autophagy, inflammation, and apoptosis.
      Pathological pregnancies, such as preeclampsia, are associated with placental
      H/R, and decreased placental melatonin synthesis as well as lower melatonin
      levels in the placenta and maternal plasma. However, the effects of exogenous
      melatonin on inflammation and autophagy induced by pregnancy complications
      associated with H/R await investigation. This study aimed to determine as to
      whether melatonin protects human primary villous trophoblasts against H/R-induced
      autophagy, inflammation, and apoptosis. Human primary villous cytotrophoblasts
      were isolated and immunopurified from normal term placentas. These cells were
      then exposed or not to 1 mmol/L melatonin for 72 hour in normoxia (8% O2 ),
      thereby inducing differentiation into syncytiotrophoblast that was then exposed
      to H/R (0.5% O2 , for 4 hour) or normoxia. H/R decreased endogenous melatonin
      synthesis (by 68%) and interleukin (IL)-10 levels (by 72%), coupled to increased
      tumor necrosis factor (TNF) (by 114%), IL-6 (by 55%), and NFkappaB (by 399%),
      compared to normoxia. Melatonin treatment reversed the H/R effect, restoring IL
      10, TNF, and IL-6 levels to those of the normoxia condition. Melatonin, as well
      as NFkappaB inhibition, enhanced autophagy activation, consequently increasing
      syncytiotrophoblast survival in H/R conditions. This study suggests that H/R,
      which is present in pregnancy complications, inhibits endogenous melatonin
      production, thereby contributing to reduced syncytiotrophoblast viability.
      Results indicate that exogenous melatonin treatment may afford protection against
      H/R-induced damage, thereby enhancing placental cell survival, and contributing
      to improved fetal outcomes.

PMID- 30091211
TI  - Validation of Gelbond(r) high-throughput alkaline and Fpg-modified comet assay
      using a linear mixed model.
AB  - Even if the comet assay has been widely used for decades, there is still a need
      for controlled studies and good mathematical models to assess the variability of
      the different versions of this assay and in particular to assess potential intra
      experimental variability of the high-throughput comet assay. To address this
      point, we further validate a high-throughput comet assay that uses hydrophilic
      polyester film (Gelbond(r)). Experiments were performed using human peripheral
      blood mononuclear cells (PBMC) either untreated or treated with different
      concentration of MMS (methyl methanesulfonate). A positive control for the Fpg
      (Formamidopyrimidine DNA glycosylase)-modified comet assay (Ro 19-8022 with
      light) was also included. To quantify the sources of variability of the assay,
      including intradeposit variability, instead of summarizing DNA damage on 50 cells
      from a deposit by the mean or median of their percentage DNA tail, we analyzed
      all logit-transformed data with a linear mixed model. The main source of
      variation in our experimental data is between cells within the same deposit,
      suggesting genuine variability in the response of the cells rather than variation
      caused by technical treatment of cell samples. The second source of variation is
      the inter-experimental variation (day-to-day experiment); the coefficient of this
      variation for the control was 13.6%. The variation between deposits in the same
      experiment is negligible. Moreover, there is no systematic bias because of the
      position of samples on the Gelbond(r) film nor the position of the films in the
      electrophoresis tank. This high-throughput comet assay is thus reliable for
      various applications. Environ. Mol. Mutagen. 59:595-602, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30091212
TI  - Altered fire regimes cause long-term lichen diversity losses.
AB  - Many global ecosystems have undergone shifts in fire regimes in recent decades,
      such as changes in fire size, frequency, and/or severity. Recent research shows
      that increases in fire size, frequency, and severity can lead to long-persisting
      deforestation, but the consequences of shifting fire regimes for biodiversity of
      other vegetative organisms (such as understory plants, fungi, and lichens) remain
      poorly understood. Understanding lichen responses to wildfire is particularly
      important because lichens play crucial roles in nutrient cycling and supporting
      wildlife in many ecosystems. Lichen responses to fire have been little studied,
      and most previous research has been limited to small geographic areas (e.g.
      studies of a single fire), making it difficult to establish generalizable
      patterns. To investigate long-term effects of fire severity on lichen
      communities, we sampled epiphytic lichen communities in 104 study plots across
      California's greater Sierra Nevada region in areas that burned in five wildfires,
      ranging from 4 to 16 years prior to sampling. The conifer forest ecosystems we
      studied have undergone a notable increase in fire severity in recent decades, and
      we sample across the full gradient of fire severity to infer how shifting fire
      regimes may influence landscape-level biodiversity. We find that low-severity
      fire has little to no effect on lichen communities. Areas that burned at moderate
      and high severities, however, have significantly and progressively lower lichen
      richness and abundance. Importantly, we observe very little postfire lichen
      recolonization on burned substrates even more than 15 years after fire. Our
      multivariate model suggests that the hotter, drier microclimates that occur after
      fire removes forest canopies may prevent lichen reestablishment, meaning that
      lichens are not likely to recolonize until mature trees regenerate. These
      findings suggest that altered fire regimes may cause broad and long-persisting
      landscape-scale biodiversity losses that could ultimately impact multiple trophic
      levels.

PMID- 30091213
TI  - Dietary patterns and respiratory health in adults from nine European countries
      Evidence from the GA2 LEN study.
AB  - BACKGROUND: Dietary patterns defined using principal component analysis (PCA)
      offer an alternative to the analysis of individual foods and nutrients and have
      been linked with asthma and allergic disease. However, results have not been
      reproducible in different settings. OBJECTIVE: To identify dietary patterns
      common to different European countries and examine their associations with asthma
      and allergic symptoms. METHODS: In sixteen study centers in nine European
      countries, 3206 individuals aged 15-77 years completed a common, internationally
      validated, food frequency questionnaire and a respiratory symptoms questionnaire.
      The outcomes of interest were current asthma, asthma symptoms score (derived
      based on responses to 5 asthma symptom-related questions), atopy (positive skin
      prick test). Spirometry was used to estimate forced expiratory volume in 1 second
      (FEV1 ), forced vital capacity (FVC), the FEV1 /FVC, spirometric restriction (FVC
      below the lower limit of normal (<LLN)) and FEV1 /FVC < LLN. A novel meta
      analytic approach was used to identify dietary patterns using PCA and to examine
      associations with asthma and allergic symptoms. RESULTS: Two dietary patterns
      emerged, generally correlating with the same foods in different countries: one
      associated with intake of animal proteins and carbohydrates; the other with fruit
      and vegetables. There was evidence that the former pattern was associated with a
      higher asthma score (RR 1.63, 95% CI: 1.33-2.01), current asthma (RR 2.03, 95%
      CI: 1.52-2.71), wheeze (RR 1.84, 95% CI: 1.30-2.60), atopic status (RR 1.68, 95%
      CI: 1.16-2.44) and with decreased lung function, including an FVC <LLN (RR 4.57,
      95% CI: 2.27-9.21). CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest an
      increase in sensitisation to common allergens, an increase in asthma symptoms,
      and a reduction in lung function in those eating a diet rich in animal proteins
      and carbohydrates. We found little evidence of an association between these
      outcomes and eating a diet rich in fruits and vegetables.

PMID- 30091214
TI  - Care of veterans in a non-veteran health administration hospital: What is the
      status of nursing practice after continuing education?
AB  - AIMS AND OBJECTIVES: To identify how civilian nurses are caring for military
      veterans following mandatory continuing education on veterans' mental health
      needs and to describe challenges nurses are facing in provision of that care.
      BACKGROUND: Veterans and military personnel experience mental health conditions
      at a high rate and are increasingly receiving care in civilian healthcare
      facilities. Nonmilitary providers may not be prepared to address this
      population's challenging needs. Military culture may influence the presentation
      of mental health conditions; thus, critical assessment points by nonmilitary
      medical personnel may be missed. Education is touted internationally as a means
      to address deficits, but research is lacking to support that statement. METHODS:
      Adhering to research reporting guidelines, 115 of a proposed 322 civilian nurses
      in a tertiary hospital volunteered to complete a one-time online survey that
      contained quantitative and demographic questions. Forty of 115 nurses went on to
      complete the qualitative query. Descriptive statistics summarised quantitative
      results, and constant comparative analysis was applied to qualitative responses
      for theme identification. RESULTS: The study was stopped early due to reports of
      violence from veterans upon nurses. Results showed continuing education did not
      change documentation of military status. Following mandatory continuing
      education, civilian nurses continued to describe uncertainty in how to adapt
      care, on how to interact with veterans and in how to deal with violence.
      CONCLUSION: The status of care to veterans remains insufficient, but nurses are
      asking critical questions on how to update practice. Additional support and
      research in the clinical setting is needed to promote a safe caring environment.
      RELEVANCE TO CLINICAL PRACTICE: Continuing education alone may not advance care
      of the veteran. A multipronged approach to include mandatory documentation of
      military status and coaching of providers by those experienced with the military
      way of life may be used to augment staff preparedness.

PMID- 30091215
TI  - Risk of heart failure in a population with type 2 diabetes versus a population
      without diabetes with and without coronary heart disease.
AB  - AIMS: To conduct a population-based study comparing age- and sex-specific risk
      estimates of heart failure (HF) between people with type 2 diabetes and people
      without diabetes, and to investigate the risks of HF in association with type 2
      diabetes in people with various coronary heart diseases (CHDs). MATERIALS AND
      METHODS: We used a nationally representative sample (one million people) selected
      from Taiwan's National Health Insurance (NHI) system. A total of 34 291 patients
      with type 2 diabetes were identified from ambulatory care claims in 2000, and the
      same number of age- and sex-matched controls were randomly selected from the
      registry of NHI beneficiaries in the same year. All study subjects were linked to
      inpatient claims (2000-2013) to identify the possible admissions for HF. Using a
      Cox proportional hazard regression model, we compared the relative hazards of HF
      in relation to type 2 diabetes according to various age and sex stratifications.
      We also compared the relative hazard of HF between type 2 diabetes and controls,
      with and without histories of various CHDs and coronary revascularization
      procedures. RESULTS: Compared with absence of diabetes (control group), type 2
      diabetes was significantly associated with an increased hazard of HF (adjusted
      hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.40-1.54]. In both sexes,
      those with type 2 diabetes aged <45 years had the highest increased hazard of HF,
      with an aHR of 2.54 (95% CI 1.62-3.98) and 4.12 (95% CI 2.35-7.23) for men and
      women, respectively. Compared with the control subjects without any CHD, people
      with type 2 diabetes without prior CHD had increased hazards of HF (aHR 1.54, 95%
      CI 1.41-1.68, in men and aHR 1.56, 95% CI 1.43-1.71, in women), which were
      similar to the aHRs for people without diabetes who had histories of heart
      diseases (aHR 1.60 and 1.55 for men and women, respectively). CONCLUSIONS:
      Diabetes mellitus may increase the risk of HF in both men and women, as well as
      in all age groups, especially in young people. People with type 2 diabetes
      without CHD had a similarly increased risk of HF to that of control subjects with
      CHD. Certain coronary revascularization procedures and CHDs, including
      percutaneous transluminal coronary angiography, coronary artery bypass surgery
      and acute myocardial infarction, were found to greatly increase risk of HF in
      people with type 2 diabetes.

PMID- 30091216
TI  - Evidence of latent molecular diversity determining the virulence of community
      associated MRSA USA300 clones in mice.
AB  - INTRODUCTION: The USA300 clone of community-associated MRSA is reported to be
      hypervirulent and epidemic in the United States. This clone causes a variety of
      diseases from lethal pneumonia to mild skin infections. We hypothesized that
      evolutionary diversity may exist among USA300 clones, which may link virulence
      traits with host responses and mortality rates. METHODS: USA300 isolates from
      severe pneumonia (IP) and skin infection (IS) were characterized by pulsed-field
      gel electrophoresis (PFGE) and next-generation sequencing. Their virulence traits
      and host responses were compared in a lung infection model. RESULTS: The two
      USA300 isolates were found to be identical in genomic analysis. Robust IL-6
      production, aggregation of bacteria, and hemorrhaging were observed in IP
      infected lungs, which were associated with a higher rate of mortality than that
      observed with strain IS. Few neutrophils were detected in the lungs infected with
      strain IP, even at high bacterial loads. Massive production of alpha-toxin and
      coagulase were evident during the early phase of IP infection, and robust gene
      expression of hla (alpha-toxin) and lukS-PV (Panton-Valentine leukocidin), but
      not coa, agrA, or rnaIII, was confirmed in vitro. Strain IP also induced strong
      hemolysis in red blood cells. CONCLUSIONS: The present data demonstrated latent
      diversity in the virulence of USA300 clones. Unknown regulatory mechanisms,
      probably involving a host factor(s) as a trigger, may govern the virulence
      expression and resultant high mortality in certain sub-clones of USA300.

PMID- 30091217
TI  - Comparison in outcome with tailored antibiotic prophylaxis postoperatively in
      pediatric intestinal transplant population.
AB  - BIs are ubiquitous among the pediatric intestinal transplant patient population.
      Personalizing postoperative prophylaxis antibiotic regimens may improve outcomes
      in this population. A retrospective analysis of all pediatric patients who
      underwent intestinal transplantation was evaluated to compare standardized and
      tailored regimens of antibiotics provided as prophylaxis postoperatively.
      Patients in the standard group have both shorter time to and higher rate of BIs,
      which was statistically significant (P < 0.001). Of the children who developed a
      BI, there was no statistical difference in average times to the development of a
      second BI (293 vs 119 days, P = 0.211). The tailored group had prolonged times
      until the development of a MDRO (52.6 vs 63.9 days, P = 0.677). Although not
      statistically significant, the tailored group had a propensity to present with
      gram-negative pathogens after transplant as compared to the standard regimen
      group, which presented with gram-positive pathogens (P = 0.103). Children with a
      history of an MDRO held a 7.3 (P < 0.01) times more likelihood of death within a
      year of transplant. A tailored prophylactic antibiotic regimen in the post
      transplant period appears to prolong the time to the first BI. Although the data
      do not show differences in mortality, further study may prove the impact of a
      tailored antibiotic regimen on morbidity and mortality rates.

PMID- 30091218
TI  - A novel dual glucagon-like peptide and glucagon receptor agonist SAR425899:
      Results of randomized, placebo-controlled first-in-human and first-in-patient
      trials.
AB  - AIMS: To evaluate the safety, pharmacokinetics and pharmacodynamics of SAR425899,
      a novel polypeptide, active as an agonist at both the glucagon-like peptide-1
      receptor (GLP-1R) and the glucagon receptor (GCR), in healthy volunteers and in
      overweight/obese patients with type 2 diabetes (T2D). METHODS: Subcutaneous
      administrations of SAR425899 were tested in two randomized, placebo-controlled,
      double-blind clinical trials. In the first trial, healthy overweight volunteers
      (body mass index [BMI] 25-30 kg/m2 ; n = 32) received single-ascending doses
      (0.01-0.1 mg) of SAR425899 or placebo. In the second, a multiple-ascending-dose
      trial (NCT02411825), healthy normal- to overweight volunteers (BMI 20-30 kg/m2 ;
      n = 40) and overweight/obese patients with T2D (BMI 28-42 kg/m2 ; n = 36)
      received daily doses of SAR425899 or placebo over 21 or 28 days, respectively.
      RESULTS: The most frequently reported adverse events were gastrointestinal;
      gastrointestinal side effects were less pronounced in patients with T2D compared
      with healthy volunteers. SAR425899 significantly reduced levels of fasting plasma
      glucose (P < 0.05 vs. placebo) and glycated haemoglobin (P < 0.001 versus
      placebo) in patients with T2D. Additionally, SAR425899 led to reductions in body
      weight, with a maximal reduction of 5.32 kg in healthy volunteers and 5.46 kg in
      patients with T2D (P < 0.001 vs. placebo) at end of treatment. CONCLUSIONS:
      SAR425899 was well tolerated and led to favourable glycaemic effects in patients
      with T2D and weight reduction in both healthy volunteers and patients. Whether
      dual GLP-1R/GCR agonism represents a treatment method that is superior to pure
      GLP-1R agonists for obesity and diabetes treatment remains to be confirmed.

PMID- 30091219
TI  - The study of histological changes of the arterial vascular structure after
      hyaluronidase exposure.
AB  - BACKGROUND: Hyaluronic acid (HA) filler injection is commonly used for soft
      tissue augmentation. Uncommon but serious complication from filler injection is
      vascular occlusion. Hyaluronidase enzyme can be used to dissolve HA filler.
      Evidence demonstrates that hyaluronidase can penetrate through vessel wall after
      incubation. However, studies regarding effects of hyaluronidase on vessel wall
      after intraluminal injection are limited. The objective of this study is to
      evaluate histological changes of postmortem arteries after intravascular
      injection of hyaluronidase enzyme. METHODS: This was an ex vivo experiment
      including arterial specimens from four cadavers which recently deceased within 24
      hours. All vessels were examined at baseline and then were divided into two
      groups. The first was the control group treated with normal saline and the second
      hyaluronidase-treated group was intra-luminally injected with hyaluronidase
      enzyme (1500 IU/mL). Gross and histological examination was performed at
      baseline, 30-minutes and 4 hours after. RESULTS: Gross examination of vessels
      revealed no significant difference at baseline, 30 minutes and 4 hours after
      injection in both groups. Histological examinations at baseline and 30 minutes
      after injection revealed viable endothelial cells in both experimental and NSS
      control group. At 4 hours after hyaluronidase injection, two of the four arterial
      specimens had degeneration of endothelial cell, and one artery showed separation
      of tunica intima from tunica media. CONCLUSION: There were endothelial injuries
      in the arterial specimens after intravascular concentrated hyaluronidase
      injection.

PMID- 30091220
TI  - Human Corneal Tissue Model for Nociceptive Assessments.
AB  - New in vitro tissue models to mimic in vivo conditions are needed to provide
      insight into mechanisms involved in peripheral pain responses, potential
      therapeutic strategies to address these responses, and to replace animal models
      for such indications. For example, the rabbit cornea Draize test has become the
      standard method used for decades to screen ophthalmic drug and consumer product
      toxicity. In vitro tissue models with functional innervation have the potential
      to replace in vivo animal testing and provide sophisticated bench tools to study
      ocular nociception and its amelioration. Herein, full thickness, innervated, 3D
      human corneal tissues are grown under physiologically relevant culture conditions
      to study nociceptive-related responses, by mimicking ocular environmental cues,
      including intraocular pressure (IOP) and tear flow (TF). Capsaicin, a chili
      pepper-derived irritant known to cause a burning sensation in mammalian tissues
      is utilized as a nociceptive stimulant to induce pain, while subsequent serum
      treatment is used to mimic healing. Pain mediators released upon capsaicin
      stimulation and cell regrowth after serum treatment are characterized to assess
      ocular responses in this new, innervated, human corneal tissue system for
      comparison of outcomes to established animal and related responses.

PMID- 30091221
TI  - PBPK Models for CYP3A4 and P-gp DDI Prediction: A Modeling Network of Rifampicin,
      Itraconazole, Clarithromycin, Midazolam, Alfentanil, and Digoxin.
AB  - According to current US Food and Drug Administration (FDA) and European Medicines
      Agency (EMA) guidance documents, physiologically based pharmacokinetic (PBPK)
      modeling is a powerful tool to explore and quantitatively predict drug-drug
      interactions (DDIs) and may offer an alternative to dedicated clinical trials.
      This study provides whole-body PBPK models of rifampicin, itraconazole,
      clarithromycin, midazolam, alfentanil, and digoxin within the Open Systems
      Pharmacology (OSP) Suite. All models were built independently, coupled using
      reported interaction parameters, and mutually evaluated to verify their
      predictive performance by simulating published clinical DDI studies. In total,
      112 studies were used for model development and 57 studies for DDI prediction.
      93% of the predicted area under the plasma concentration-time curve (AUC) ratios
      and 94% of the peak plasma concentration (Cmax ) ratios are within twofold of the
      observed values. This study lays a cornerstone for the qualification of the OSP
      platform with regard to reliable PBPK predictions of enzyme-mediated and
      transporter-mediated DDIs during model-informed drug development. All presented
      models are provided open-source and transparently documented.

PMID- 30091222
TI  - Bullous CD4+ CD8+ adult T-cell leukemia/lymphoma, a rare diagnostically
      challenging cutaneous variant.

PMID- 30091224
TI  - Missed opportunities and potentially misleading results in maternal mortality
      study.

PMID- 30091223
TI  - Magnetic resonance imaging as a prognostic disability marker in clinically
      isolated syndrome: A systematic review.
AB  - Magnetic resonance imaging (MRI) is the key prognostic tool in people with a
      clinically isolated syndrome (CIS). There is increasing interest in treating
      people following a CIS in the hope that conversion to multiple sclerosis (MS)
      will be prevented and future disability reduced. So far, the prognostic value of
      MRI for disability following a CIS has not been evaluated systematically. We
      systematically searched MEDLINE and EMBASE. Cohort studies were selected if they
      reported associations of MRI and disability following a CIS, included at least 50
      people with a CIS at baseline, had at least 5 years of follow-up and obtained at
      least one structural MRI measurement (T1 lesions, T2 lesions, T1 contrast
      enhancing lesions or brain atrophy). We assessed the studies for quality and
      rated the completeness of MRI reporting. In total, 13 studies were identified
      reporting on the following: T2 lesion number and volume, T2 infratentorial lesion
      number and volume, T1 contrast-enhancing lesions and grey matter fraction. T2
      brain lesion number determined soon after the occurrence of a CIS was associated
      with disability progression after 5-7 years, with an increased risk when 10 or
      more lesions were present. Infratentorial lesions were also associated with a
      higher risk of subsequent disability. The number and distribution of MRI-visible
      lesions soon after a CIS are associated with disability later on, and may offer
      additional useful information when making treatment decisions in people with
      early MS. Further work is required to determine whether other measures have a
      higher predictive potential.

PMID- 30091225
TI  - Reaction to 'Integrating smoking cessation care in alcohol and other drug
      treatment settings using an organizational change intervention: a systematic
      review' by Skelton et al. (2018).

PMID- 30091226
TI  - SGLT2 inhibitors in Type 1 diabetes: is this the future?

PMID- 30091227
TI  - Carbaboranylation of Truncated C-Terminal Neuropeptide Y Analogue Leads to Full
      hY1 Receptor Agonism.
AB  - The human Y1 receptor is overexpressed in breast tumour cells and is, therefore,
      a valuable target for site-selective drug delivery. The well-established hY1 R
      selective ligand [Phe7,Pro34]NPY has been used to couple to drugs but its length
      of 36 amino acids also implies complex synthesis and high production costs.
      Therefore, shorter ligands are desirable. However, truncated versions of
      neuropeptide Y (NPY) usually result in reduced binding, antagonists, or only
      partial G-protein-biased agonists. Herein, we report on a nonamer peptide derived
      from the C terminus of NPY that is modified by a carbaborane, which is able to
      activate hY1 R fully in terms of G-protein activation but also arrestin
      recruitment and internalisation. We provide evidence that this unique behaviour
      is due to the bulky nature of the carbaborane cluster, which might address a
      specific second binding pocket in hY1 R that is crucial for arrestin recruitment.
      Thus, this study helps in deciphering ligand-induced onset of different pathways
      in hY1 R mediated signalling.

PMID- 30091228
TI  - Synthesis of Surface-Modification-Oriented Nanosized Molybdenum Disulfide with
      High Peroxidase-Like Catalytic Activity for H2 O2 and Cholesterol Detection.
AB  - Abnormal H2 O2 and cholesterol levels are closely related to many diseases. This
      work reports a facile process for the synthesis of oxidized glutathione (GSSG)
      modified MoS2 nanosheets (MoS2 -GSSG NSs). The biocompatible MoS2 -GSSG NSs have
      good dispersibility and high affinity to the substrate 3,3',5,5'
      tetramethylbenzidine (TMB), which is beneficial for improving peroxidase-like
      catalytic activity of MoS2 . The high peroxidase-like activity of MoS2 -GSSG NSs
      was applied as a robust nanoplatform for low-cost, rapid, and highly effective
      colorimetric detection of H2 O2 and total/free cholesterol. Moreover, the
      peroxidase-like catalytic mechanism was studied by the steady-state kinetics
      method. The catalytic activity was remarkably high at a wide range of pH (2.4
      7.0) and temperature values (25-70  degrees C). The cholesterol was catalyzed by
      cholesterol oxidase (ChOx) in the presence of O2 to generate H2 O2 , which
      oxidized TMB to generate a blue-colored product (oxTMB) under the catalysis of
      MoS2 -GSSG NSs. The detection limit (DL) of total cholesterol and H2 O2 was as
      low as 5.36 and 0.51 MUm, respectively. The linear ranges for detecting
      cholesterol and H2 O2 were from 5.36 to 800 MUm and from 0.51 to 50 MUm,
      respectively. This method was also successfully applied to the detection of
      cholesterol in serum. The detection concentration of total cholesterol was
      consistent with that of the value detected by the blood biochemical method used
      in the clinic.

PMID- 30091229
TI  - Proteomic analysis of hypothalamus and liver proteins affected by dietary l
      arginine supplementation in laying hens.
AB  - The goal of this study was to investigate the influence of l-arginine (l-Arg)
      supplementation on diet-induced changes in hypothalamus and liver proteome of
      laying hens. Layers were fed either an isonitrogenous control diet or a l-Arg
      diet. The test included a 2-week acclimation period and a 12-week experimental
      period. Eight layers per group were sacrificed at terminal of the experiment
      underwent 12 fasting. Blood and tissue samples of hypothalamus and liver were
      collected for further analysis. The levels of serum nitric oxide and hypothalamus
      neuropeptide Y of layers in l-Arg group were increased in comparison with those
      in control group. Quantitative proteomic analyses showed that a total of 3,715
      hypothalamus proteins (235 differentially expressed) and 3797 liver proteins (373
      differentially expressed) were detected between control and l-Arg-fed groups. A
      further enriched Gene Ontology term analysis of proteins found that 17
      hypothalamus proteins (11 upregulated and six downregulated) and 29 liver
      proteins (14 upregulated and 15 downregulated) were altered differentially
      between the two groups. Our findings revealed the changes in metabolic and
      hormonal signals in central nervous system and peripheral tissues by responding
      to l-Arg feeding, which provides a possible way to gain a better understanding of
      l-Arg function in laying hens.

PMID- 30091230
TI  - Spectroscopic investigations of nanosized Cr3+ doped Sc2-x Inx (WO4 )3 : A new
      promising laser material.
AB  - Chromium(III) doped nanosized Sc2-x Inx (WO4 )3 , (x = 0-2) solid solutions were
      prepared by the co-precipitation/calcination method. The obtained powders were
      characterized using X-ray diffraction (XRD), electron paramagnetic resonance
      (EPR), infrared (IR), absorption and luminescence spectra. X-ray analysis showed
      that the compounds are pure solid solutions with orthorhombic symmetry at x
      values 0 and 0.5 and with monoclinic symmetry for x values 1.0, 1.5 and 2.0. The
      calculated crystallite size ranged from about 20 to 110 nm, except for Sc2 (WO4
      )3 characterized by considerably larger sizes. IR spectra of the solid solutions
      contain the characteristic vibrations of the WO4 and MeO6 , (Me = Sc, In)
      polyhedra, building the Sc2 (WO4 )3 and In2 (WO4 )3 structures. EPR analysis
      proved the presence of isolated Cr3+ ions in the crystal field with rhombic
      symmetry. The presence of Cr3+ in sites with weak and strong crystal field was
      revealed by absorption and luminescence spectra. This study demonstrates the
      effect of hosts crystal symmetry, particles size and doping concentration on the
      luminescence properties.

PMID- 30091231
TI  - Technical challenges and clinical relevance of single antigen bead C1q/C3d
      testing and IgG subclass analysis of human leukocyte antigen antibodies.
AB  - Luminex single antigen bead assays revolutionized human leukocyte antigen (HLA)
      antibody detection owing to their superior sensitivity compared to conventional
      methods. Nevertheless, the advent of higher sensitivity came at the expense of
      difficulty in clinical decision-making, since not all luminex detectable
      antibodies are clinically relevant. Therefore, new tools such as C1q/C3d assays
      and IgG subclass analysis emerged with the aim to discriminate the inert
      antibodies from the deleterious ones. Here, we provide an overview on the
      technical challenges related to these different HLA antibody detection systems
      and briefly refer to the recent literature regarding the clinical relevance of
      these assays, mainly in the field of kidney transplantation.

PMID- 30091232
TI  - NOCARDIOSIS: 7-YEAR experience at an australian tertiary hospital.
AB  - BACKGROUND: Nocardiosis has historically been reported in immunocompromised
      patients, but Australian epidemiological and antimicrobial susceptibility data
      are limited. AIMS: To describe the epidemiology, diagnosis and initial treatment
      of nocardiosis in an Australian tertiary hospital over 7 years. METHODS: In this
      retrospective study, all positive cultures for Nocardia species from any site
      isolated at the Alfred Hospital, Melbourne, between January 1 2010 and December
      31 2016 were identified, and corresponding laboratory data and medical records
      reviewed. RESULTS: 68 non-duplicate isolates were identified from 67 patients.
      Common predisposing factors were chronic lung disease (38/67; 57%), organ,
      particularly lung, transplantation (13/67; 19%), and solid organ malignancy
      (6/67; 9%); 12% (8/67) of patients had no identifiable systemic risk factors. 79%
      (53/67) of patients had pulmonary nocardiosis only. Nocardia nova was the most
      commonly isolated species (20/68; 29%). In 48% (32/67) of patients, Nocardia
      species were isolated only on specific mycobacterial media. All tested species
      were susceptible to sulfamethoxazole-trimethoprim and amikacin, with the majority
      (58/63; 92%) susceptible to imipenem. All-cause mortality rates at 6 and 12
      months where data were available were 15% (10/66 patients) and 22% (14/64
      patients) respectively. CONCLUSION: In the largest Australian series in 25 years,
      nocardiosis predominantly affected patients with chronic lung disease or impaired
      cell-mediated immunity. A significant proportion of organisms from pulmonary
      sites were isolated on mycobacterial culture media only, suggesting that its use
      may improve yield. Isolates remain highly susceptible to sulfamethoxazole
      trimethoprim, amikacin and imipenem, whilst other agents should be used only
      after confirmation of in vitro susceptibility. This article is protected by
      copyright. All rights reserved.

PMID- 30091233
TI  - The toxicological impact of some avermectins on human erythrocytes glutathione S
      transferase enzyme.
AB  - The drugs of the class avermectins are antiparasitic agents, which are widely
      used in medical and agricultural fields, especially in veterinary medicine. The
      aim of this study was to investigate the inhibitory effects of avermectin
      derivatives such as abamectin, doramectin, eprinomectin, ivermectin, and
      moxidectin, which are used for internal and external mammalian parasites.
      Glutathione S-transferase (GST, E.C. 2.5.1.18) was purified from fresh human
      erythrocytes. The purification of the GST enzyme was performed separately by
      affinity chromatography with a yield of 34.81% and 117.94-fold purification. The
      control of the pure GST enzyme was performed by sodium dodecyl sulphate
      polyacrylamide gel electrophoresis, and a single band was obtained. The IC50
      values were approximately 0.31, 0.39, 0.13, 0.44, and 0.73 mM for abamectin,
      doramectin, eprinomectin, ivermectin, and moxidectin, and the Ki values were 0.32
      +/- 0.06, 0.39 +/- 0.09, 0.13 +/- 0.03, 0.44 +/- 0.02, 0.73 +/- 0.04 mM,
      respectively. This data revealed that the tested avermectins showed significant
      inhibitory effects on the GST enzyme.

PMID- 30091234
TI  - Use of factor concentrates for the management of perioperative bleeding: reply.

PMID- 30091235
TI  - A Contemporary Review of Severe Aortic Stenosis.
AB  - Severe aortic stenosis (AS) is the most common form of valvular heart disease in
      the developed world with a rising prevalence due to an ageing Australian
      population. Transcatheter aortic valve implantation (TAVI) offers a less invasive
      option for the treatment of severe AS with evidence supporting of TAVI compared
      to medical therapy in inoperable patients, and superior to surgical aortic valve
      replacement (SAVR) in high-risk patients. Equal outcomes have been observed in
      all-comer intermediate risk populations. The Heart Team utilises a shared
      decision-making approach between physicians and surgeons in risk stratifying
      patients and reduces the intrinsic bias that may occur if decisions are made in
      isolation. Geriatric assessment is useful in identifying pre-operative frailty, a
      major risk factor for death post aortic valve intervention. In severe AS, a
      decision can be made collaboratively to pursue TAVI, SAVR, a Ross Procedure, or
      conservative management. The learning curve associated with TAVI has improved
      markedly with overall complication rates decreasing around the world.
      Contemporary changes in practice such as conscious sedation without general
      anaesthesia, expedited recovery and early discharge will likely improve cost
      effectiveness. In 2018, TAVI is a well-established procedure in Australia that
      has revolutionised the management of severe AS. In the future with an expanding
      elderly population, the number of patients to benefit from transcatheter
      therapies for severe AS is hypothesised to increase 4-10 fold. Heart Team
      assessment is crucial in patients with severe AS to direct appropriate
      management. This article is protected by copyright. All rights reserved.

PMID- 30091236
TI  - The Roc-COR tandem domain of leucine-rich repeat kinase 2 forms dimers and
      exhibits conventional Ras-like GTPase properties.
AB  - The Parkinson's disease (PD)-causative leucine-rich repeat kinase 2 (LRRK2)
      belongs to the Roco family of G-proteins comprising a Ras-of-complex (Roc) domain
      followed by a C-terminal of Roc (COR) domain in tandem (called Roc-COR domain).
      Two prokaryotic Roc-COR domains have been characterized as 'G proteins activated
      by guanine nucleotide-dependent dimerization' (GADs), which require dimerization
      for activation of their GTPase activity and bind guanine nucleotides with
      relatively low affinities. Additionally, LRRK2 Roc domain in isolation binds
      guanine nucleotides with relatively low affinities. As such, LRRK2 GTPase domain
      was predicted to be a GAD. Herein, we describe the design and high-level
      expression of human LRRK2 Roc-COR domain (LRRK2 Roc-COR). Biochemical analyses of
      LRRK2 Roc-COR reveal that it forms homodimers, with the C-terminal portion of COR
      mediating its dimerization. Furthermore, it co-purifies and binds Mg2+ GTP/GDP at
      1 : 1 stoichiometry, and it hydrolyzes GTP with Km  and kcat  of 22 nM and 4.70 *
      10-4  min-1 ,  respectively. Thus, even though LRRK2 Roc-COR forms GAD-like
      homodimers, it exhibits conventional Ras-like GTPase properties, with high
      affinity binding of Mg2+ -GTP/GDP and low intrinsic catalytic activity. The PD
      causative Y1699C mutation mapped to the COR domain was previously reported to
      reduce the GTPase activity of full-length LRRK2. In contrast, this mutation
      induces no change in the GTPase activity, and only slight perturbations in the
      secondary structure contents of LRRK2 Roc-COR. As this mutation does not directly
      affect the GTPase activity of the isolated Roc-COR tandem, it is possible that
      the effects of this mutation on full-length LRRK2 occur via other functional
      domains. Open Practices Open Science: This manuscript was awarded with the Open
      Materials Badge. For more information see: https://cos.io/our-services/open
      science-badges/.

PMID- 30091237
TI  - New HLA-C alleles identified in two donors from the Colombian public umbilical
      cord blood bank.
AB  - Two novel HLA-class I alleles discovered: HLA-C*08:162 and HLA-C*03:296:02.

PMID- 30091238
TI  - Association of survival and hyperthermia after rt-PA for ischemic stroke.
AB  - BACKGROUND: Hyperthermia in patients with acute ischemic stroke is associated
      with poor outcome. Although previous studies have shown a negative effect on
      functional outcome, even in patients treated with intravenous recombinant tissue
      plasminogen activator (rt-PA), the effect on survival remains unclear. AIMS OF
      THE STUDY: The aim of this study was to evaluate the association between the
      functional and survival prognosis and hyperthermia in patients with acute
      ischemic stroke treated with rt-PA. METHODS: We studied 120 patients treated with
      rt-PA from 2306 consecutive Japanese patients with acute cerebral infarction at
      Aomori Prefectural Central Hospital between December 2009 and March 2017. We
      defined hyperthermia as >=38 degrees C within 72 hours after rt-PA
      administration. Propensity score matching was used to compare 34 non-hyperthermia
      and hyperthermia patient pairs. RESULTS: Final modified Rankin Scale scores were
      higher in the hyperthermia group than in the non-hyperthermia group. In addition,
      the Kaplan-Meier model showed that the non-hyperthermia group had significantly
      better survival rates than the hyperthermia group (hazard ratio, 5.3; 95%
      confidence intervals, 1.2-24.8). CONCLUSIONS: Hyperthermia within 3 days after rt
      PA is associated with poor functional prognosis and survival outcome in patients
      with acute cerebral infarction.

PMID- 30091239
TI  - Significance of hepatic resection and adjuvant hepatic arterial infusion
      chemotherapy for hepatocellular carcinoma with portal vein tumor thrombus in the
      first branch of portal vein and the main portal trunk: a project study for
      hepatic surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery.
AB  - BACKGROUND: The prognosis of hepatocellular carcinoma (HCC) with tumor thrombus
      in the major portal vein (PV) is extremely poor. The purpose of this study was to
      clarify the impact of hepatic resection for HCC with tumor thrombus in the major
      PV. PATIENTS: Four hundred patients undergoing macroscopic curative resection for
      HCC involving the first branch or trunk of the PV between 2001 and 2010 at the 22
      institutions were enrolled. We examined the effect of adjuvant hepatic arterial
      infusion chemotherapy (HAIC) on prognosis and validated the prognostic index
      consisting of ascites, prothrombin activity, and maximal tumor diameter. RESULTS:
      Median survival time (MST) and 5-year overall survival rate were 21.5 months and
      25.7%. MST of HAIC group was longer than that of non-HAIC group (28.1 months vs.
      18.7 months, P = 0.0024). Significant prognostic factors for overall survival
      were PIVKA-II, tumor diameter, and adjuvant HAIC. MST for patients with
      prognostic index 0, 1, 2, and 3 was 39.0, 21.1, 18.9, and 5.7 months,
      respectively (P = 0.005). CONCLUSIONS: Macroscopic curative resection with
      adjuvant HAIC might provide better survival outcome. Furthermore, the prognostic
      index was useful to select adequate treatment modalities for patients with HCC
      with tumor thrombosis in the major PV.

PMID- 30091240
TI  - Hospice Care of Veterans in Medicare Advantage and Traditional Medicare: A Risk
      Adjusted Analysis.
AB  - OBJECTIVES: To compare the quality of end-of-life care in Medicare Advantage (MA)
      and traditional Medicare (TM), specifically, receipt and length of hospice care.
      DESIGN: Retrospective analysis of administrative data. SETTING: Hospice care.
      PARTICIPANTS: Veterans dually enrolled in the Veterans Health Administration
      (VHA) and MA or TM who died between 2008 and 2013 (N = 1,515,441). MEASUREMENTS:
      Outcomes studied included use and duration of hospice care. Use of a VHA-enrolled
      population allowed for risk adjustment that is otherwise challenging when
      studying MA. RESULTS: Adjusted analyses revealed that MA beneficiaries were more
      likely to receive hospice than TM beneficiaries; results corroborate published
      non-risk-adjusted analyses. MA beneficiaries had shorter hospice duration; this
      is an opposite direction of effect than non-risk-adjusted analyses. Results were
      robust to multiple sensitivity analyses limiting the cohort to individuals in MA
      and TM who had equal opportunity for their comorbidities to be captured. Removing
      risk adjustment resulted in results that mirrored those in the existing published
      literature. CONCLUSION: Our work provides two important insights regarding MA
      that are important to consider as enrollment in this insurance mechanism grows.
      First, MA beneficiaries received poorer-quality end-of-life care than TM
      beneficiaries, as ascertained by exposure to hospice. Second, any comparisons
      made between MA and TM require proper risk adjustment to obtain correct
      directions of effect. We encourage the Centers for Medicare & Medicaid Services
      to make comorbidity data specific to MA enrollees available to researchers for
      these purposes.

PMID- 30091241
TI  - The effectiveness of fishery net dips: Advice for the improvement of biosecurity
      measures.
AB  - Disease poses a major threat to aquaculture and commercial and recreational
      fisheries globally. Biosecurity measures have been implemented; however,
      empirical evidence of their efficacy in situ is lacking. Here, we present the
      results from a study conducted to examine the effectiveness of disinfectant net
      dips. Samples were collected from disinfectant net dips at 25 recreational
      fisheries in south-west England and assessed to determine (a) the level of
      bacterial contamination and (b) the reduction in titre of a target virus
      (infectious pancreatic necrosis virus, IPNV) following a contact time of 2 and 5
      min. In addition, the study examined the reduction in target virus titre
      following exposure to laboratory prepared Virkon(r) , representing "clean,"
      "dirty" and "diluted and dirty" conditions, for 2 and 5 min. Bacterial
      contamination was high in 64% of disinfectant samples, and, 76% of disinfectant
      samples did not effectively reduce the target virus titre in 2 or 5 min. Virus
      titre was successfully reduced following exposure to laboratory prepared
      Virkon(r) for 2 or 5 min, although dilution and contamination reduced the
      effectiveness. These results suggest that disinfectant net dips may not be
      working effectively on a high proportion of fishery sites. We provide
      recommendations for improving biosecurity.

PMID- 30091242
TI  - Dissecting the nucleotide binding properties of the septins from S. cerevisiae.
AB  - Septins are a conserved family of guanosine triphosphate (GTP)-binding proteins
      that assemble into an ordered array of filaments at the mother bud neck in
      Saccharomyces cerevisiae cells. They are present in all higher eukaryotes except
      plants. Septins belong structurally to the P-Loop nucleoside triphosphatase
      (NTPases) like Rab and Ras. However, unlike other small guanosine triphosphatase
      (GTPases) septins are supposed to act as scaffolds rather than signalling
      mediators. This is why they are considered as the fourth class of cytoskeletal
      proteins. It is assumed that septins fulfil their functions independently of the
      bound nucleotide. The role of guanosine diphosphosphate (GDP) and GTP binding and
      subsequent hydrolysis was controversial debated in the last couple of years. Lack
      of crystal structures of yeast septin subunits or rods and difficulties to
      isolate single monomeric septin subunits often hindered the correlation of
      results obtained from in vivo studies with biochemical data. Recently, nucleotide
      binding and hydrolysis was connected to the formation of septin rods from its
      subunits. However, the evidence was only indirectly obtained through the use of
      septin mutants in the context of intact cells. We provide here mechanistic
      insight into the nucleotide binding of the yeast septins by in vitro assays using
      purified septin rods and building blocks, thereby adding further insights to the
      already available models on septin filament formation.

PMID- 30091243
TI  - Immunological profile of teeth with inflammatory periapical disease from chronic
      liver disease patients.
AB  - AIM: To evaluate the mRNA expression levels of the cytokines interferon-gamma,
      tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-10, IL-6, VEGF, and AGT
      and the chemokine CCL2/MCP-1 in periapical interstitial fluid associated with
      root canal infections before and after the reduction of the bacterial load using
      a cleaning procedure. METHODOLOGY: The case group included 11 patients with
      chronic liver disease, and the control group included 11 healthy patients.
      Clinical samples were taken from teeth with pulp necrosis. After cleaning and
      drying the canal, three paper points were introduced into the root canal and
      passed through the root apex (2 mm) into the periapical tissues for 1 min. The
      samples were collected immediately after root canal cleaning and 7 days later to
      characterize those gene expression levels using real-time PCR. The data were
      subjected to the Shapiro-Wilk and the Wilcoxon tests. RESULTS: In the control
      group, significantly increased expression of the pro-inflammatory cytokines IFN
      gamma and TNF-alpha was observed in teeth with restrained bacterial loads (day 7)
      (P < 0.05). Similarly, increased TNF-alpha expression was found on day 7 in the
      liver group (P < 0.05). No differences were observed in the expression levels of
      the IL-1beta, IL-10 and, IL-6, MCP-1/CCL-2 and VEGF between the first collection
      (day 0) and second collection (day 7), over time in either group. CONCLUSION:
      Chronic liver disease patients exhibited sufficient immunologic ability showing
      relatively similar expression levels of cytokines, chemokines and angiogenic
      factors in periapical samples compared with the responses from no-chronic liver
      disease patients. The outcomes of this study suggest that liver impairment did
      not compromise the periapical immune response.

PMID- 30091244
TI  - Dilating and fracturing side struts of open cell stents frequently used in
      pediatric cardiac interventions-An in vitro study.
AB  - BACKGROUND: Open cell stents are frequently used in interventional therapy of
      congenital heart disease. Overstenting of vessel branches may necessitate strut
      dilation. METHODS AND RESULTS: The strut size achievable in Bard Valeo and Cook
      Formula stents, and the pressure necessary to fracture struts was assessed. In
      addition, a self expanding stent (Optimed SinusflexDS) was also tested. With the
      original balloon at nominal pressure, in Valeo stents side struts could be
      dilated to approximately 90% of the nominal stent diameter, in Formula stents to
      approximately 80%. With larger high pressure woven balloons, strut size increased
      to approximately 125% in Valeo stents, and to approximately 105% in the Formula.
      Strut fracture can connect two adjoining struts. Pressures were dependent on the
      balloon utilized. Sidestruts of the Sinusflex could lastingly overdilated with
      large balloons only. CONCLUSION: Dilation and overdilation of side struts in open
      cell stents can be achieved. Dependent on the clinical context, the original
      balloon used to place the premounted stent can be used to achieve strut dilation,
      but woven high pressure balloons maybe safer for patients. Should a larger
      diameter be required, these high pressure woven balloons can achieve bigger
      diameters and even strut fracture.

PMID- 30091245
TI  - Bacillus amyloliquefaciens CotA degradation of the lignin model compound
      guaiacylglycerol-beta-guaiacyl ether.
AB  - The cotA gene from Bacillus amyloliquefaciens MN-13 was cloned and expressed in
      Escherichia coli Transetta. Nucleotide sequence analysis showed an open reading
      frame of 1542 bp encoding a polypeptide comprised of 513 amino acids. The
      degradation of lignin model compounds by recombinant CotA was investigated by
      HPLC-MS with guaiacylglycerol-beta-guaiacyl ether as the substrate. The compounds
      including guaiacol, 3-(4-hydro-3-methoxyphenyl)-3-oxo-propanol and 4-hydro-3
      methoxy acetophenone detected by HPLC-MS verified the rupture of beta-O-4 bond
      and oxidation Calpha bond of guaiacylglycerol-beta-guaiacyl ether by CotA. 4
      vinylguaiacol and 1-(4-hydroxy-3-methoxyl phenyl)-1-(2-methoxyl) phenoxyl
      ethylene were first time found in the degradation products of guaiacylglycerol
      beta-guaiacyl ether. The appearance of 4-vinylguaiacol and 4-hydro-3-methoxy
      acetophenone confirmed the cleavage of Cbeta-Cgamma bond. 1-(4-hydroxy-3-methoxyl
      phenyl)-2-(2-methoxyl) phenoxyl ethylene was coupled by the radical reaction of 4
      vinylguaiacol with guaiacol. Otherwise, no corresponding degradation product was
      found to give a proof of cleavage of Calpha-Cbeta bond in guaiacylglycerol-beta
      guaiacyl ether by CotA.

PMID- 30091246
TI  - An Investigation into the Acquired Capability for Suicide.
AB  - OBJECTIVE: The acquired capability for suicide (ACS) is one of the most important
      breakthroughs in suicide research. ACS refers to an individual's increased
      fearlessness about death over time from experiencing painful and provocative
      events (PPE) and is based on opponent-process theory-a habituation model. Few
      studies have investigated how ACS develops and found that ACS remained relatively
      stagnant. METHOD: This study sought to expand these findings by observing how ACS
      develops in two cross-sectional data sets involving high-risk nonclinical samples
      of physicians (n = 419) and veterinary students (n = 124). Participants completed
      online questionnaires assessing both general PPEs (e.g., witnessing abuse) and
      job-specific PPEs (e.g., exposure to euthanasia), as well as ACS. RESULTS: Our
      results partially replicated prior findings indicating that more PPEs do not
      significantly affect ACS. CONCLUSIONS: Limitations of this study include the use
      of cross-sectional data and self-report measures. These results, in combination
      with existing models of habituation, suggest ACS may not progress linearly.

PMID- 30091247
TI  - Dreaming of a learning task is associated with enhanced memory consolidation:
      Replication in an overnight sleep study.
AB  - Sleep following learning benefits memory. One model attributes this effect to the
      iterative "reactivation" of memory traces in the sleeping brain, demonstrated in
      animal models. Although technical limitations prohibit using the same methods to
      observe memory reactivation in the human brain, the study of mental activity
      during sleep provides an alternative method of observing memory activation during
      sleep. In fact, the content of dream experience may reflect the process of memory
      reactivation and consolidation in the sleeping brain. In line with this
      hypothesis, we previously reported that dreaming about a spatial learning task
      during a nap strongly predicts subsequent performance improvements. Here, we
      replicate this observation in an overnight sleep study, for the first time
      demonstrating that pre-sleep training on a virtual maze navigation task is
      reflected in dreams reported from all phases of sleep, with unambiguous
      representation of the task in dream content associated with improved next-morning
      performance. These observations are consistent with reactivation-based models of
      memory consolidation in sleep, confirming our earlier finding that the cognitive
      level activation of recent experience during sleep is associated with subsequent
      performance gains.

PMID- 30091248
TI  - Analysis of mutation in the rat Pig-a assay: II. Studies with bone marrow
      granulocytes.
AB  - The in vivo erythrocyte Pig-a gene mutation assay measures the phenotypic loss of
      GPI-anchored surface markers. Molecular analysis of the marker-deficient
      erythrocytes cannot provide direct proof that the mutant phenotype is due to
      mutation in the Pig-a gene because mammalian erythrocytes lack genomic DNA.
      Granulocytes are nucleated cells that originate from myeloid progenitor cells in
      bone marrow as is the case for erythrocytes, and thus analysis of Pig-a mutation
      in bone marrow granulocytes can provide information about the source of mutations
      detected in the erythrocyte Pig-a assay. We developed a flow cytometric Pig-a
      assay for bone marrow granulocytes and evaluated granulocyte Pig-a mutant
      frequencies in bone marrow from male rats treated acutely with N-ethyl-N
      nitrosourea (ENU). Bone marrow cells from these rats were stained with anti-CD11b
      for identifying granulocytes and anti-CD48 for detecting the Pig-a mutant
      phenotype. The average Pig-a mutant frequency in granulocyte precursors of
      control rats was 8.42 * 10-6 , whereas in ENU-treated rats it was 567.13 * 10-6 .
      CD11b-positive/CD48-deficient mutant cells were enriched using magnetic
      separation and sorted into small pools for sequencing. While there were no Pig-a
      mutations found in sorted CD48-positive wild-type cells, Pig-a mutations were
      detected in mutant granulocyte precursors. The most frequent mutation observed
      was T->A transversion, followed by T->C transition and T->G transversion, with
      the mutated T on the nontranscribed DNA strand. While the spectrum of mutations
      in bone marrow granulocytes was similar to that of erythroid cells, different Pig
      a mutations were found in mutant-phenotype granulocytes and erythroids from the
      same bone marrow samples, suggesting that most Pig-a mutations were induced in
      bone marrow cells after commitment to either the granulocyte or erythroid
      developmental pathway. Environ. Mol. Mutagen. 59:733-741, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30091249
TI  - Three validation studies of the personality assessment inventory short form.
AB  - OBJECTIVE: We examined the psychometric properties of the Personality Assessment
      Inventory-Short Form (PAI-SF). METHOD: Study 1 compared single-session short and
      full form PAI profiles of 200 outpatients, Study 2 examined PAI forms of 107
      nonclinical adults across two administrations, and Study 3 compared correlations
      between full and short form scales and extratest variables. RESULTS: Study 1
      correlations between short and full form scales ranged from 0.85 to 0.95 (Mdn =
      0.91), with lower correlations, ranging from 0.59 to 0.86 for clinical scales
      (Mdn = 0.82), in Study 2. In Study 3 only 4 of 34 correlations differed
      significantly between extratest variables and the PAI versus the PAI-SF.
      CONCLUSIONS: These results indicate favorable psychometric properties of the PAI
      SF.

PMID- 30091250
TI  - Morphology Control Enables Efficient Ternary Organic Solar Cells.
AB  - Ternary organic solar cells are promising alternatives to the binary counterpart
      due to their potential in achieving high performance. Although a growing number
      of ternary organic solar cells are recently reported, less effort is devoted to
      morphology control. Here, ternary organic solar cells are fabricated using a wide
      bandgap polymer PBT1-C as the donor, a crystalline fused-ring electron acceptor
      ITIC-2Cl, and an amorphous fullerene derivative indene-C60 bisadduct (ICBA) as
      the acceptor. It is found that ICBA can disturb pi-pi interactions of the
      crystalline ITIC-2Cl molecules in ternary blends and then help to form more
      uniform morphology. As a result, incorporation of 20% ICBA in the PBT1-C:ITIC-2Cl
      blend enables efficient charge dissociation, negligible bimolecular
      recombination, and balanced charge carrier mobilities. An impressive power
      conversion efficiency (PCE) of 13.4%, with a high fill factor (FF) of 76.8%, is
      eventually achieved, which represents one of the highest PCEs reported so far for
      organic solar cells. The results manifest that the adoption of amorphous
      fullerene acceptor is an effective approach to optimizing the ternary blend
      morphology and thereby increases the solar cell performance.

PMID- 30091251
TI  - Meeting patients' spiritual needs during end-of-life care: A qualitative study of
      nurses' and healthcare professionals' perceptions of spiritual care training.
AB  - AIMS AND OBJECTIVES: To explore nurses' and healthcare professionals' perceptions
      of spiritual care and the impact of spiritual care training on their clinical
      roles. BACKGROUND: Many nurses and healthcare professionals feel unprepared and
      lack confidence, competence and skills, to recognise, assess and address
      patients' spiritual issues. Patients with unmet spiritual needs are at increased
      risk of poorer psychological outcomes, diminished quality of life and reduced
      sense of spiritual peace. There are implications for patient care if nurses and
      healthcare professionals cannot attend to patients' spiritual needs. DESIGN: A
      qualitative methodology was adopted. METHODS: Recruitment was purposive. A total
      of 21 generalist and specialist nursing and healthcare professionals from North
      West and South West England, who undertook spiritual care training between 2015
      2017, were recruited. Participants were required to be a minimum of 3 months
      posttraining. Digitally audio-recorded semistructured interviews lasting 11-40
      min were undertaken in 2016-2017. Data were subjected to thematic analysis.
      Ethical committee approval was obtained. COREQ reporting guidelines were
      utilised. RESULTS: Two main themes were identified, recognising spirituality,
      with subthemes of what spirituality means and what matters, and supporting
      spiritual needs, with subthemes of recognition of spiritual distress,
      communication skills, not having the answers and going beyond the physical.
      CONCLUSIONS: Supporting patients as they approach the end of life needs a skilled
      workforce; acknowledging the importance of spiritual care and having skills to
      address it are central to delivery of best holistic care. RELEVANCE TO CLINICAL
      PRACTICE: Spiritual care is as important as physical care and supporting patients
      spiritually as they approach the end of life is vital. Appropriately trained,
      nurses and healthcare professionals are better able to assess, explore and meet
      patients' spiritual needs.

PMID- 30091252
TI  - Developing a model of factors that influence meeting the needs of family with a
      relative in ICU.
AB  - AIM: To develop a model of factors influencing meeting family needs when a
      relative was admitted to the intensive care unit (ICU). BACKGROUND: Studies
      identify individual factors impact on the needs of family members with a relative
      in ICU. No studies have reported on relationships between these factors and/or
      the extent of influence of multiple factors on family needs. DESIGN:
      Observational, correlational, and predictive study design. METHODS: Data were
      collected from August 2013 to June 2014 using validated scales and a demographic
      tool. The setting was a large tertiary referral hospital in Brisbane, Australia.
      Structural equation modelling was undertaken. RESULTS: One hundred and seventy
      ICU family members participated. Factors included in the developed model were
      consistent with the literature. Family member anxiety had direct and significant
      influence on ICU family needs (beta = 0.21). Gender was also found to have direct
      influence (beta = 0.19), suggesting female family members were more likely to
      report needs being met. Family member coping self-efficacy (beta = -0.40) and
      family member depression (beta = -0.33) were mediating variables. DISCUSSION:
      Interventions to meet family needs within the ICU should take into account family
      member levels of anxiety, depression, and coping self-efficacy with consideration
      of gender. Further model validation is required to confirm findings.

PMID- 30091253
TI  - Italian consensus report on the aesthetic use of onabotulinum toxin A.
AB  - BACKGROUND: The aesthetic treatment of facial and neck wrinkles with botulinum
      toxin is constantly increasing, thus making it necessary to collect procedures
      guidelines for the use of botulinum toxin in the treatment of wrinkles and/or
      cosmetic defects. METHODS: A group of nine Italian doctors, plastic and maxillo
      facial surgeons, dermatologists and aesthetic physicians, experts in face and
      neck aesthetic treatments with onabotulinum toxin A, discussed on procedures used
      in their clinical practice. From the data collected and discussed by the board,
      some recommendations on aesthetic treatment with onabotulinum toxin A were
      developed. RESULTS: Recommendations have been made on pretreatment,
      reconstitution of onabotulinum toxin A, as well as on treatment procedures, in
      terms of injection sites and total dose of onabotulinum toxin A for the following
      indications: glabellar lines, crown's feet lines, forehead lines, eyebrow
      shaping, lower orbicularis oculi hypertrophy, bunny lines, sagging nasal tip,
      gummy smile, masseter hypertrophy, perioral lines, marionette lines, hypertonic
      mentalis, and platysma bands. CONCLUSIONS: The use of onabotulinum toxin A in the
      aesthetic field requires careful initial assessment of the patient in its
      complexity and individuality. Moreover, this treatment needs the use of
      standardized procedures to achieve the effectiveness and safety of onabotulinum
      toxin A in clinical practice.

PMID- 30091254
TI  - Stilbene biosynthesis and gene expression in response to methyl jasmonate and
      continuous light treatment in Vitis vinifera cv. Malvasia del Lazio and Vitis
      rupestris Du Lot cell cultures.
AB  - Vitis rupestris is used as rootstock or to obtain hybrids with Vitis vinifera,
      due to its resistance to certain pathogens. Its resistance mechanisms are poorly
      understood, while it is known that stilbene neo-synthesis is a central defense
      strategy in V. vinifera. In the present study, the response to methyl jasmonate
      (MeJa) and light treatment in terms of stilbene biosynthesis and the expression
      of genes involved in polyphenol biosynthesis was investigated in V. vinifera and
      V. rupestris cells. The two species exhibited a similar constitutive stilbene
      content [2.50-2.80 mg g-1 dry weight (DW)], which greatly increased in response
      to elicitation (8.97-11.90 mg g-1 DW). In V. vinifera, continuous light treatment
      amplified the effect of MeJa, with a stilbene production that had never
      previously been obtained (26.49 mg g-1 DW). By contrast, it suppressed the effect
      of MeJa in V. rupestris. Gene expression was consistent with stilbene production
      in V. vinifera, whereas discrepancies were recorded in V. rupestris that could be
      explained by the synthesis of stilbenes that had never before been analyzed in
      this species.

PMID- 30091256
TI  - Comparing the cost of preparing matched unrelated donor and TCR alpha+ beta+
      /CD19+ depleted donor material for pediatric hematopoietic stem cell transplants
      in Australia.
AB  - Use of TCR alpha+ beta+ /CD19+ depletion in a pediatric setting has improved the
      utility of haploidentical donor material, resulting in better rates of
      engraftment, lower rates of graft vs host disease (GVHD), and improved transplant
      related mortality. There are currently no data available on the costs of TCR
      alpha+ beta+ /CD19+ depletion. This study assessed the costs of acquiring and
      preparing TCR alpha+ beta+ /CD19+ depleted haploidentical donor cells in
      comparison with matched unrelated donor (MUD) products for use in pediatric
      patients in Australia. Data from four pediatric transplant centers were used to
      estimate the resources required for donor work-up, graft acquisition, and
      laboratory procedures for graft preparation. Information on MUD work-up and graft
      acquisition was also acquired from these sites and from the national coordinating
      donor center in Australia. Australian-specific prices and fees were used to
      estimate total average costs for each transplant type, converted to USD.
      Preparation of graft material (including work-up, acquisition, and laboratory
      processes) costs USD 28 963 for TCR alpha+ beta+ /CD19+ depleted haploidentical
      grafts and USD 27 297 for MUD grafts. The estimated difference of USD 1666 is
      largely attributed to the process and consumables to perform TCR alpha+ beta+
      /CD19+ depletion. Given the potential for recipients of TCR alpha+ beta+ /CD19+
      depleted grafts to require minimal GVHD prophylaxis and experience less
      transplant-related morbidity and mortality, use of TCR alpha+ beta+ /CD19+
      depletion appears favorable despite the higher initial cost. Research is
      currently ongoing to assess the clinical effectiveness and potential cost
      effectiveness of TCR alpha+ beta+ /CD19+ depletion over a patients' lifetime.

PMID- 30091257
TI  - Outcomes of Patients Admitted to Hospital Medical Units with Back Pain.
AB  - BACKGROUND: Hospital admissions for patients with back pain are increasing.
      Despite their significant contribution to the health-care burden they remain
      largely unstudied. AIM: To investigate the management and clinical outcomes of
      patients with acute back pain admitted to hospital under general medicine units
      when compared to a rheumatology unit. METHODS: A 36-month retrospective,
      observational study on patients presenting to the Emergency Department with back
      pain who were subsequently admitted to 1 of 3 General Medicine Units (GM) or a
      Rheumatology Unit (RU). MAIN OUTCOME MEASURES: Differences in patient
      demographics, management and clinical outcomes were assessed using Chi-Squared
      tests for categorical variables and Kruskall Wallis tests for continuous
      variables. Multivariate associations of two primary outcomes, length of stay
      (LOS) and complications were examined using generalised estimating equations.
      RESULTS: Data from 712 admissions from 594 patients across the 4 inpatient units
      were used for this study. Common discharge diagnoses were
      musculoskeletal/nonspecific back pain (41%), disc related illness (22%),
      vertebral fracture (14%) and sciatica (14%). Non-English speaking background, age
      >=80 years, disc related disease, vertebral fracture and sciatica were
      statistically significantly associated with both increased LOS and complications.
      The presence of comorbidities was associated with more complications. GM
      admission was associated with a longer LOS and more complications than RU
      admission. CONCLUSION: Multiple factors associated with an increased LOS and
      complications were identified, including older patients, patients of non-English
      speaking background. Given the observed variations in back pain management
      between general and specialty units, strategies to standardise care should be
      considered. This article is protected by copyright. All rights reserved.

PMID- 30091255
TI  - Caenorhabditis elegans as an emerging model system in environmental epigenetics.
AB  - The roundworm Caenorhabitis elegans has been an established model organism for
      the study of genetics and developmental biology, including studies of
      transcriptional regulation, since the 1970s. This model organism has continued to
      be used as a classical model system as the field of transcriptional regulation
      has expanded to include scientific advances in epigenetics and chromatin biology.
      In the last several decades, C. elegans has emerged as a powerful model for
      environmental toxicology, particularly for the study of chemical genotoxicity.
      Here, we outline the utility and applicability of C. elegans as a powerful model
      organism for mechanistic studies of environmental influences on the epigenome.
      Our goal in this article is to inform the field of environmental epigenetics of
      the strengths and limitations of the well-established C. elegans model organism
      as an emerging model for medium-throughput, in vivo exploration of the role of
      exogenous chemical stimuli in transcriptional regulation, developmental
      epigenetic reprogramming, and epigenetic memory and inheritance. As the field of
      environmental epigenetics matures, and research begins to map mechanisms
      underlying observed associations, new toolkits and model systems, particularly
      manipulable, scalable in vivo systems that accurately model human transcriptional
      regulatory circuits, will provide an essential experimental bridge between in
      vitro biochemical experiments and mammalian model systems. Environ. Mol. Mutagen.
      59:560-575, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30091258
TI  - Regional neuronal activity in patients with relapsing remitting multiple
      sclerosis.
AB  - OBJECTIVES: Although interferon-beta is an established drug for relapsing
      remitting multiple sclerosis (RRMS), its impact on neuronal activity is not well
      understood. METHODS: We investigated 15 patients with RRMS by [18
      F]fluorodeoxyglucose positron emission tomography (FDG-PET) to assess cerebral
      metabolic rate of glucose (CMRglc ) before interferon-beta therapy. Further, we
      performed clinical and neuropsychological investigations. In nine patients, these
      investigations were repeated after 6 months of therapy. Ten healthy controls were
      also studied. RESULTS: We found no significant differences in absolute CMRglc
      between patients and controls, or in patients before and during treatment.
      However, during treatment, relative regional glucose metabolism (rCMRlglc ) was
      decreased in cerebellum and increased in parts of left inferior parietal, temporo
      occipital, frontal cortical areas, left striatum and right insula. In untreated
      patients, higher fatigue was associated with lower rCMRlglc in portions of left
      posterior cingulate cortex, and higher depression was associated with lower
      rCMRlglc within the left superior temporal sulcus. In the pooled sample, higher
      depression was associated with higher rCMRlglc in parts of the right precuneus.
      CONCLUSIONS: Our results indicate effects of IFN-beta treatment on cerebellar,
      cortical and subcortical neuronal function. Moreover, more severe fatigue and
      depression in untreated patients seem to be associated with reduced neuronal
      activity in left posterior cingulate cortex and left superior temporal cortex,
      respectively.

PMID- 30091259
TI  - The effects of resilience and turnover intention on nurses' burnout: Findings
      from a comparative cross-sectional study.
AB  - AIMS AND OBJECTIVES: To investigate burnout among nurses from Australia and China
      and explore the effects of resilience and turnover intention on nurse burnout
      between the two countries. BACKGROUND: Nursing shortages and burnout have become
      serious problems worldwide in recent years. In both developed and developing
      countries, such as Australia and China, nurse burnout levels are high and
      therefore attract concern from nurse managers, hospital administrators, nurse
      educators and researchers. However, few studies have been conducted exploring the
      differences in burnout and its predictors between Australian and Chinese nurses,
      particularly investigating the differences in the effect sizes of the predictors.
      DESIGN: A comparative cross-sectional design was employed. METHODS: A total of
      100 Australian nurses and 197 Chinese nurses participated in the study.
      Australian participants completed an online questionnaire, while Chinese
      participants completed a hardcopy questionnaire. Burnout, resilience and turnover
      intention were measured. RESULTS: Burnout was worse for Australian participants
      than Chinese participants. Only having turnover intention significantly predicted
      burnout in Australian participants, while low resilience, having turnover
      intention and low level of regular exercise strongly predicted burnout in Chinese
      participants. The effect size of turnover intention on burnout in the Australian
      group was almost twice that of the Chinese group. CONCLUSION: The findings of
      this study show that there are differences in burnout between Australian and
      Chinese nurses. The effects of resilience and turnover intention on burnout
      between the two groups are also identified. RELEVANCE TO CLINICAL PRACTICE: The
      differences in nurse burnout and the effects of resilience and turnover intention
      on burnout should be better understood by nurse managers from Australia and
      China. Moreover, developing effective strategies relevant to their own country to
      reduce nurse burnout is recommended.

PMID- 30091260
TI  - The posterior temporal supraSMAS minimally invasive lifting technique using soft
      tissue fillers.
AB  - BACKGROUND: To investigate the effectiveness of the posterior temporal supraSMAS
      minimally invasive lifting technique and compared it to experiments performed in
      fresh human body donors by applying skin vector displacement measurement
      technology. MATERIALS AND METHODS: A total of 15 patients (14 females/1 male)
      with a mean age of 37.1 +/- 9.4 years and a mean body mass index of 21.4 +/- 3.3
      kg/m2 were included into this observational analysis. The injection procedure was
      additionally performed in 2 male and 1 female fresh body donors with a mean age
      of 85.67 +/- 9.7 years and a mean body mass index of 23.83 +/- 4.7 kg/m2 .
      Different grades of skin laxity, variable amounts of product, and the application
      with and without subcision were tested and measured via three-dimensional
      reconstructions and surface displacement vectors using Vectra software with VAM
      module. RESULTS: Esthetic outcome was rated by an independent professional
      observer and by the patient immediately after the treatment (76.67% +/- 17.6% vs
      66.67% +/- 18.1%) (P = 0.001) and after 1 month (80.00% +/- 14.0% vs 75.00% +/-
      21.1%) (P = 0.19). Skin laxity, subcision, and the application of more than 1.0
      cc per side resulted in our experimental setting in a smaller magnitude of skin
      displacement vectors indicating a reduced lifting effect. CONCLUSION: The
      posterior temporal supraSMAS minimally invasive lifting procedure seems to be a
      valid technique to treat temporal volume loss and to reduce the signs of age
      related changes in the middle and lower face, ie "marionett line" and jowl
      deformity.

PMID- 30091261
TI  - Identification of Mucorales in patients with proven invasive mucormycosis by
      polymerase chain reaction in tissue samples.
AB  - BACKGROUND: Accurate diagnosis of mucormycosis, a life-threatening fungal
      infection, remains a challenge for physicians. OBJECTIVES: To identify the
      causative Mucorales in fresh clinical samples and formalin-fixed paraffin
      embedded (FFPE) samples of patients with proven mucormycosis by molecular method.
      PATIENTS/METHODS: Fresh clinical samples of patients with proven mucormycosis
      according to the EORTC/MSG criteria admitted between 2015 and 2017 and
      histopathologically proven FFPE archives collected during 2004-2007 and 2015-2017
      from Mazandaran University-affiliated hospitals of northern Iran were included.
      Seminested PCR targeting the 18S rDNA of Mucorales and ITS region was performed,
      and PCR products were then sequenced. RESULTS: While culture was positive only in
      5 of 9 (56%) of fresh specimen cases, PCR was positive in all 9 (100%)
      histologically proven mucormycosis. Ten of 18 (56%) FFPE samples were PCR
      positive. Overall, Mucorales PCR was positive in 19 of 27 (70%) samples.
      Mucorales species were Rhizopus arrhizus in 16 (84%) cases, R.
      arrhizus/Amylomyces rouxii in 2 (10.5%) cases and Rhizopus stolonifer in one case
      (5.5%). Among 27 mucormycosis cases, 25 (93%) cases were rhinocerebral, and 2
      (7%) cases were disseminated. Diabetes mellitus (74%) and neutropaenia (63%) were
      the main risk factors. CONCLUSIONS: Seminested PCR targeting 18S rDNA region of
      Mucorales is useful for identification of the causative agents of mucormycosis.

PMID- 30091262
TI  - Histopathology and external examination of heavily parasitized Lost River Sucker
      Deltistes luxatus (Cope 1879) and Shortnose Sucker Chasmistes brevirostris (Cope
      1879) from Upper Klamath Lake, Oregon.
AB  - Shortnose Sucker (Chasimistes brevirostris) and Lost River Sucker (Deltistes
      luxatus) are endemic to the Upper Klamath Basin of Southern Oregon and Northern
      California, and their populations are in decline. We used histopathology and
      external examination of 140 and external examination only of 310 underyearling
      suckers collected in 2013, 2015 and 2016 to document pathological changes,
      particularly those relating to parasites. The most severe infection was caused by
      a Contracaecum sp., infecting the atrium of 8%-33% of Shortnose Suckers. The most
      prevalent infections were caused by Bolbophorus sp. metacercariae in the muscle
      of Shortnose Suckers (21%-63%) and Lernaea cyprinacea in the skin and muscle of
      Lost River Suckers (30%-81%). Histology detected Bolbophorus in only 5% of cases
      where it was not seen externally. Three myxozoans were observed; a Parvicapsula
      sp. in the renal tubules (10%), a Myxobolus sp. in the intestinal mucosa (2%) and
      an unusual multicellular, presporogonic myxozoan in the intestinal lumen of one
      sucker. Severe gill epithelial hyperplasia was observed in several fish collected
      in 2016. Trichodinids and Ichthyobodo sp. were observed on some of the gills, but
      absent in many of the fish with severe lesions. A histiocytic sarcoma was
      observed in sucker.

PMID- 30091263
TI  - MRGPRX2 is negatively targeted by SCF and IL-4 to diminish pseudo-allergic
      stimulation of skin mast cells in culture.
AB  - MRGPRX2 was recently uncovered as the "missing link" in clinically relevant mast
      cell (MC) activation explaining previously puzzling phenomena. It is the receptor
      for various endogenous ligands and exogenous compounds alike, whose binding
      evokes rapid degranulation much like allergen-mediated exocytosis. While the
      perceivable outcomes are similar, the two activation routes differ regarding
      mechanism and regulation. We recently reported that acute SCF administration
      curbs responses evoked by MRGPRX2 in human skin MCs. Maintenance of MCs in
      culture requires the presence of MC supportive factors and renders the cells
      functionally and molecularly unequal to ex vivo counterparts. Here, we asked
      whether expansion in culture impacts the pseudo-allergic route, and if so, what
      contribution SCF and IL-4 play in this scenario. We report that the in vitro
      micromilieu dampens (but does not erase) pseudo-allergic responses and that this
      is accompanied by strongly reduced MRGPRX2 expression. Withdrawal of SCF or IL-4
      individually, but most potently of both collectively, partially reinstates the
      MRGPRX2 pathway, revealing that SCF and IL-4 make negative adjustments to the
      pseudo-allergic pathway. Under all conditions, the FcepsilonRI-triggered route
      showed the inverse pattern of regulation, substantiating that allergic and pseudo
      allergic MC activation can obey opposite rules, hinting at possible competition
      between them.

PMID- 30091264
TI  - Reliably picking the best endpoint.
AB  - Endpoint selection in clinical trials involves a variety of considerations. One
      important consideration is the sample size required to power a future clinical
      trial. In this work, we define the sample size ratio, theta, as the ratio of
      sample sizes required to power a future trial. We consider in detail the setting
      of continuous endpoints where a Welch's t-statistic is used to analyze the data.
      We develop an estimator that depends on the squared ratio of estimated
      standardized treatment effects, and the quadrant on the plane in which they fall.
      We evaluate bootstrap and profile likelihood methods for construction of
      confidence intervals. Generalizations to other endpoints and testing of nonnested
      models are discussed. The methods are applied to analyze two different assays
      that measure antibody abundance using data from an Ebola vaccine field trial.

PMID- 30091265
TI  - Neuropathy following spinal nerve injury shares features with the irritable
      nociceptor phenotype: A back-translational study of oxcarbazepine.
AB  - BACKGROUND: The term 'irritable nociceptor' was coined to describe neuropathic
      patients characterized by evoked hypersensitivity and preservation of primary
      afferent fibres. Oxcarbazepine is largely ineffectual in an overall patient
      population, but has clear efficacy in a subgroup with the irritable nociceptor
      profile. We examine whether neuropathy in rats induced by spinal nerve injury
      shares overlapping pharmacological sensitivity with the irritable nociceptor
      phenotype using drugs that target sodium channels. METHODS: In vivo
      electrophysiology was performed in anaesthetized spinal nerve ligated (SNL) and
      sham-operated rats to record from wide dynamic range (WDR) neurones in the
      ventral posterolateral thalamus (VPL) and dorsal horn. RESULTS: In neuropathic
      rats, spontaneous activity in the VPL was substantially attenuated by spinal
      lidocaine, an effect that was absent in sham rats. The former measure was in part
      dependent on ongoing peripheral activity as intraplantar lidocaine also reduced
      aberrant spontaneous thalamic firing. Systemic oxcarbazepine had no effect on
      wind-up of dorsal horn neurones in sham and SNL rats. However, in SNL rats,
      oxcarbazepine markedly inhibited punctate mechanical-, dynamic brush- and cold
      evoked neuronal responses in the VPL and dorsal horn, with minimal effects on
      heat-evoked responses. In addition, oxcarbazepine inhibited spontaneous activity
      in the VPL. Intraplantar injection of the active metabolite licarbazepine
      replicated the effects of systemic oxcarbazepine, supporting a peripheral locus
      of action. CONCLUSIONS: We provide evidence that ongoing activity in primary
      afferent fibres drives spontaneous thalamic firing after spinal nerve injury and
      that oxcarbazepine through a peripheral mechanism exhibits modality-selective
      inhibitory effects on sensory neuronal processing. SIGNIFICANCE: The inhibitory
      effects of lidocaine and oxcarbazepine in this rat model of neuropathy resemble
      the clinical observations in the irritable nociceptor patient subgroup and
      support a mechanism-based rationale for bench-to-bedside translation when
      screening novel drugs.

PMID- 30091266
TI  - Dose-response association between the triglycerides: High-density lipoprotein
      cholesterol ratio and type 2 diabetes mellitus risk: The rural Chinese cohort
      study and meta-analysis.
AB  - BACKGROUND: High triglyceride (TG) and low high-density lipoprotein cholesterol
      (HDL-C) levels are traditional risk factors for type 2 diabetes mellitus (T2DM).
      This study evaluated the dose-response relationship between the TG/HDL-C ratio
      and T2DM risk. METHODS: The study included 11 946 adults without baseline
      diabetes from the Rural Chinese Cohort Study. Cox proportional hazards regression
      was used to investigate the association between the TG/HDL-C ratio and T2DM. The
      dose-response relationship was evaluated by restricted cubic spline analysis. In
      addition, pooled odds ratios (OR) were calculated with a random-effects model in
      a meta-analysis including the present study and another three eligible articles.
      RESULTS: During 2007-14, 618 patients with T2DM were identified (9.68/1000 person
      years). People in the highest TG/HDL-C ratio quartile had a higher T2DM risk than
      those in the lowest quartile (adjusted hazard ratio [aHR] 2.11, 95% confidence
      interval [CI] 1.55-2.86); however, the association between the TG/HDL-C ratio and
      T2DM was stronger in females than males (aHR 1.27 [95% CI 1.16-1.39; and 1.19
      [95% CI 1.04-1.37], respectively). In body mass index-specific analysis, the
      association was stronger in normal weight than overweight/obese people. The dose
      response meta-analysis showed that a 1-unit increment in the TG/HDL-C ratio
      increased the T2DM risk by 28% (95% CI 20%-36%), with a positive linear
      relationship (Plinear  = 0.326). CONCLUSIONS: The TG/HDL-C ratio was an
      independent risk factor of T2DM, especially in females, and linearly increased
      the risk of T2DM; thus, it may be a useful indicator to identify future T2DM.

PMID- 30091267
TI  - Comparative analysis of decidual and peripheral immune cells and immune
      checkpoint molecules during pregnancy in wild-type and PACAP-deficient mice.
AB  - PROBLEM: PACAP is a neuropeptide having a major relevance in the nervous system
      and in several peripheral organs including those of the reproductive system.
      PACAP-deficient mice have several morphological, biochemical, behavioral defects,
      and show reduced fertility. Female reproductive functions such as fertility,
      mating behavior, maternal behaviors, and implantation alterations have been
      widely investigated, but no comparative immune analyses are available in pregnant
      wild-type (WT) and PACAP knockout (KO) mice. METHODS OF STUDY: Therefore, we
      performed a detailed immunophenotyping of decidual and peripheral immune cells
      and investigated the expression of two immune-checkpoint molecules by immune
      cells together with immunohistochemistry detecting Galectin-9 in placental
      tissues. We investigated the percentage of numerous immune cell populations in
      the periphery and in the decidua of pregnant mice. RESULTS: We demonstrated a
      significant increase in the frequency of decidual Gal-9+ Th cells obtained from
      PACAP KO mice compared to the decidua of WT mice. We could not determine
      statistical differences in TIM-3 and programmed cell death-1 expression by
      different immune cells in the decidua and in the periphery between WT and KO
      mice. In conclusion, we could not find any significant alteration either in the
      distribution or in the cytotoxicity of the investigated decidual immune cells
      which could elucidate any reproductive alterations in PACAP KO mice. CONCLUSION:
      The only remarkable finding is the recruitment of Gal-9+ Th cells to the decidua
      promoting local immune homeostasis in PACAP KO mice, which nevertheless cannot
      explain the reduced fertility observed in these mice.

PMID- 30091268
TI  - Progression of transthyretin (TTR) amyloidosis in donors and recipients after
      domino liver transplantation-a prospective single-center cohort study.
AB  - Liver transplantation (LT) is the first-line therapy in patients with
      transthyretin (TTR) amyloidosis and progressive familial amyloid polyneuropathy
      (FAP). Explanted organs from these patients can be used for domino liver
      transplantation (DLT). After DLT, de novo amyloidosis may develop in domino
      recipients (DR). Data were collected prospectively in a transplant database.
      Electroneurography by nerve conduction velocity (NCV), quantitative sensory
      testing, heart rate variability (HRV), sympathetic skin response, orthostatic
      reaction (tilt table test), transthoracic echocardiography, cardiac MRI and organ
      biopsy results were evaluated. The cohort included 24 FAP- (11 Val30Met, 13
      nonVal30Met) and 23 DR-patients. DR symptoms referred to post-DLT only, while
      those of FAP patients were both pre- and post-transplantation. Symptoms of TTR
      amyloidosis in Val30Met and Non-Val30Met patients pre- and post-LT were similarly
      distributed. Biopsy-proven de novo amyloidosis occurred in 4/23 DR after a mean
      observation of 10 years. Analysis for manifestations of amyloidosis only included
      patients with available 5-year follow-up data (n = 13 FAP, n = 12 DR). Compared
      to Val30Met FAP patients pre-LT, Val30Met DR patients had better NCV (P = 0.04)
      and HRV (P = 0.015). In the Non-Val30Met group no differences were found between
      DR and FAP patients pre-LT. TTR-amyloidosis symptoms showed no differences in FAP
      patients pre- and 5 years post-LT, irrespective of Val30Met status. In DR
      patients, de novo amyloidosis occurred earlier than expected. Therefore,
      recipients for DLT need to be carefully selected and followed.

PMID- 30091269
TI  - New and Revised Policies for Alcoholism: Clinical and Experimental Research
      (ACER).

PMID- 30091270
TI  - Competitive control of endoglucanase gene engXCA expression in the plant pathogen
      Xanthomonas campestris by the global transcriptional regulators HpaR1 and Clp.
AB  - Transcriptional regulators are key players in pathways that allow bacteria to
      alter gene expression in response to environmental conditions. However, work to
      understand how such transcriptional regulatory networks interact in bacterial
      plant pathogens is limited. Here, in the phytopathogen Xanthomonas campestris, we
      demonstrate that the global transcriptional regulator HpaR1 influences many of
      the same genes as another global regulator Clp, including the engXCA gene that
      encodes extracellular endoglucanase. We demonstrate that HpaR1 facilitates the
      binding of RNA polymerase to the engXCA promoter. In addition, we show that HpaR1
      binds directly to the engXCA promoter. Furthermore, our in vitro tests
      characterize two binding sites for Clp within the engXCA promoter. Interestingly,
      one of these sites overlaps with the HpaR1 binding site. Mobility shift assays
      reveal that HpaR1 has greater affinity for binding to the engXCA promoter. This
      observation is supported by promoter activity assays, which show that the engXCA
      expression level is lower when both HpaR1 and Clp are present together, rather
      than alone. The data also reveal that HpaR1 and Clp activate engXCA gene
      expression by binding directly to its promoter. This transcriptional activation
      is modulated as both regulators compete to bind to overlapping sites on the
      engXCA promoter. Bioinformatics analysis suggests that this mechanism may be used
      broadly in Xanthomonas campestris pv. campestris (Xcc) and is probably widespread
      in Xanthomonads and, potentially, other bacteria. Taken together, these data
      support a novel mechanism of competitive activation by two global regulators of
      virulence gene expression in Xcc which is probably widespread in Xanthomonads
      and, potentially, other bacteria.

PMID- 30091272
TI  - Analysis of mutation in the rat Pig-a assay: I) studies with bone marrow
      erythroid cells.
AB  - We have established a flow cytometry-based Pig-a assay for rat bone marrow
      erythroid cells (BMEs). The BME Pig-a assay uses a DNA-specific stain and two
      antibodies: one against the transmembrane transferrin receptor (CD71 marker) and
      the other against the GPI-anchored complement inhibitory protein (CD59 marker).
      In F344 male rats treated acutely with a total of 120 mg/kg of N-ethyl-N
      nitrosourea (ENU) the frequency of CD59-deficient phenotypically mutant BMEs
      increased approximately 24-fold compared to the rats concurrently treated with
      the vehicle. Such an increase of mutant BMEs coincides with increases of CD59
      deficient reticulocytes measured in rats treated with similar doses of ENU.
      Sequence analysis of the endogenous X-linked Pig-a gene of CD59-deficient BMEs
      revealed that they are Pig-a mutants. The spectrum of ENU-induced Pig-a mutations
      in these BMEs was consistent with the in vivo mutagenic signature of ENU: 73% of
      mutations occurred at A:T basepairs, with the mutated T on the nontranscribed
      strand of the gene. T->A transversion was the most frequent mutation followed by
      T->C transition; no deletion or insertion mutations were present in the spectrum.
      Since BMEs are precursors of peripheral red blood cells, our findings suggest
      that CD59-deficient erythrocytes measured in the flow cytometric erythrocyte Pig
      a assay develop from BMEs containing mutations in the Pig-a gene. Thus, the
      erythrocyte Pig-a assay detects mutation in the Pig-a gene. Environ. Mol.
      Mutagen. 59:722-732, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30091271
TI  - Outcomes of endovascular thrombectomy with and without bridging thrombolysis for
      acute large vessel occlusion ischaemic stroke.
AB  - INTRODUCTION: Endovascular thrombectomy (EVT) for management of large vessel
      occlusion (LVO) acute ischaemic stroke (AIS) is now current best practice. The
      aim of this study was to determine if bridging intravenous alteplase therapy
      confers any clinical benefit. METHODS: A retrospective study of patients treated
      with EVT for LVO was performed. Outcomes were compared between patients receiving
      thrombolysis and EVT with EVT alone. Primary endpoints were reperfusion rate, 90
      day functional outcome and mortality using the modified Rankin scale (mRS) and
      symptomatic intracranial haemorrhage (sICH). RESULTS: A total of 355 patients who
      underwent EVT were included: 210 with thrombolysis (59%) and 145 without (41%).
      The reperfusion rate was higher in the group receiving IV tPA (unadjusted OR 2.2,
      95% CI: 1.29-3.73, p=0.004) although this effect was attenuated when all
      variables were considered (adjusted OR [AOR] 1.22, 95% CI: 0.60-2.5, p=0.580).
      The percentage achieving functional independence (mRS 0-2) at 90-days was higher
      in patients who received bridging IV tPA (AOR 2.17, 95% CI:1.06-4.44, p=0.033).
      There was no significant difference in major complications including sICH (AOR
      1.4, 95% CI: 0.51-3.83, p=0.512). There was lower 90-day mortality in the
      bridging IV tPA group (AOR 0.79, 95% CI: 0.36-1.74, p=0.551). Fewer thrombectomy
      passes (2 versus 3, p=0.012) were required to achieve successful reperfusion in
      the IV tPA group. Successful reperfusion (mTICI >=2b) was the strongest predictor
      for 90-day functional independence (AOR 10.4, 95% CI:3.6-29.7, p<0.001).
      CONCLUSIONS: Our study supports the current practice of administering intravenous
      alteplase before endovascular therapy. This article is protected by copyright.
      All rights reserved.

PMID- 30091273
TI  - Infliximab and adalimumab concentrations and anti-drug antibodies in inflammatory
      bowel disease control using New Zealand assays.
AB  - BACKGROUND AND AIM: We aimed to correlate IBD disease activity in New Zealand
      patients with trough concentrations of infliximab and adalimumab using a locally
      developed enzyme-linked immunosorbent assay (ELISA), and anti-drug antibodies
      (ADA) using competitive-binding ELISA and homogeneous mobility shift assay
      (HMSA), to establish threshold concentrations. METHODS: Patients with ulcerative
      colitis (UC) and Crohn's disease (CD) from Christchurch and Dunedin on anti-TNF
      drugs >12 weeks were enrolled. Trough blood samples were assayed for drug and ADA
      concentrations. Other data included quality of life, blood count, CRP, albumin,
      renal function and disease activity indices. RESULTS: Of 103 patients, 53 were on
      infliximab (36 CD, 15 UC, 2 indeterminate) and 50 adalimumab (48 CD, 2 UC).
      Median (range) infliximab and adalimumab concentrations were 10.5 (0-41) and
      9.61mg/L (0-30). CD remission, CDAI <150, correlated with infliximab and
      adalimumab concentration in CD (infliximab p=0.03, adalimumab p=0.04), with too
      few UC patients for analysis. ROC analysis suggested a threshold value of 5.1
      mg/L for distinguishing active disease from remission for infliximab and 7.3 mg/L
      for adalimumab in CD. Of 13 patients with infliximab < 2 mg/L, 10 were ADA
      positive by HMSA, including 5 with neutralising antibodies using ELISA. Of 6 with
      adalimumab <2 mg/L, 3 were ADA positive using HMSA, including 1 with neutralising
      antibodies. CONCLUSIONS: Using the New Zealand ELISA assay, threshold
      concentrations of 5mg/L for infliximab and 7mg/L for adalimumab are suggested to
      aid dosing decisions, consistent with results internationally. Both neutralising
      (ELISA) and non-neutralising ADA (HMSA) associated with low drug concentrations.
      This article is protected by copyright. All rights reserved.

PMID- 30091274
TI  - Antinociception by intrathecal delivery of the novel non-opioid 1-amino-1
      cyclobutanecarboxylic acid.
AB  - BACKGROUND: Neuraxial opioids are widely used for intraoperative and post
      operative analgesia. The risk of severe adverse effects including respiratory
      depression accompanies this analgesia, prompting the need for effective non
      opioid alternatives. Systemic 1-amino-1-cyclobutanecarboxylic acid showed promise
      in preliminary studies to produce antinociception without observable toxicity.
      However, the effects of 1-amino-1-cyclobutanecarboxylic acid after intrathecal
      administration are unknown. The aim of this study was to determine whether
      intrathecal administration of 1-amino-1-cyclobutanecarboxylic acid produces
      antinociceptive effects in murine models and to elucidate its site and receptor
      mechanism of action. METHODS: Female CD-1 mice were randomized to receive
      intrathecal, intraperitoneal and intraplantar injections of 1-amino-1
      cyclobutanecarboxylic acid. Animals receiving intrathecal injections were
      anaesthetized and injected between L5 and L6. Animals then received an
      intraplantar injection of 10% hypertonic saline into the right hindpaw and were
      video-recorded for 30 min. Videos were analyzed by a blinded observer who
      determined the duration that animals exhibited nocifensive responses. RESULTS:
      Intrathecal or intraperitoneal administration of 1-amino-1-cyclobutanecarboxylic
      acid reduced the time that animals exhibited nocifensive behaviour, whereas
      intraplantar administration produced no effect. The effects of intrathecal 1
      amino-1-cyclobutanecarboxylic acid were restricted in dermatomal distribution,
      reversible and produced little or no depression of respiratory rate. An NMDA
      antagonist blocked antinociception, while mu-opioid or GABAB antagonists did not
      prevent ACBC antinociception. CONCLUSIONS: Intrathecal 1-amino-1
      cyclobutanecarboxylic acid in mice produces robust, brief antinociceptive effects
      with a dermatomal distribution corresponding to the lumbar site of
      administration. This amino acid merits further exploration as a non-opioid
      neuraxial analgesic with little or no respiratory side effects. SIGNIFICANCE: The
      novel, non-opioid analgesic, 1-amino-1-cyclobutanecarboxylic acid, produced
      robust, reversible and localized antinociception in murine models of pain. This
      study provides evidence supporting further investigation and development of 1
      amino-1-cyclobutanecarboxylic acid as a non-opioid spinal analgesic.

PMID- 30091276
TI  - Primary Biliary Cholangitis Guidance Update: Implications for Liver
      Transplantation.

PMID- 30091275
TI  - Effect of sleep deprivation on emotional working memory.
AB  - The emotional dysregulation and impaired working memory found after sleep loss
      can have severe implications for our daily functioning. Considering the
      intertwined relationship between emotion and cognition in stimuli processing,
      there could be further implications of sleep deprivation in high-complex
      emotional situations. Although studied separately, this interaction between
      emotion and cognitive processes has been neglected in sleep research. The aim of
      the present study was to investigate the effect of 1 night of sleep deprivation
      on emotional working memory. Sixty-one healthy participants (mean age: 23.4
      years) were either sleep deprived for 1 night (n = 30) or had a normal night's
      sleep (n = 31). They performed an N-back task with two levels of working memory
      load (1-back and 3-back) using positive, neutral and negative picture scenes.
      Sleep deprivation, compared with full night sleep, impaired emotional working
      memory accuracy, but not reaction times. The sleep-deprived participants, but not
      the controls, responded faster to positive than to negative and neutral pictures.
      The effect of sleep deprivation was similar for both high and low working memory
      loads. The results showed that although detrimental in terms of accuracy, sleep
      deprivation did not impair working memory speed. In fact, our findings indicate
      that positive stimuli may facilitate working memory processing speed after sleep
      deprivation.

PMID- 30091277
TI  - Layered Heterostructures of Ultrathin Polymeric Carbon Nitride and ZnIn2 S4
      Nanosheets for Photocatalytic CO2 Reduction.
AB  - The rational construction of heterostructures by using layered semiconductors
      with two-dimensional (2D) nanosheet configurations is promising to improve the
      efficiency of CO2 photoreduction. Herein, the fabrication of layered
      heterojunction photocatalysts (PCN/ZnIn2 S4 ) by in situ growth of 2D ZnIn2 S4
      nanosheets on the surfaces of ultrathin polymeric carbon nitride (PCN) layers is
      presented for greatly enhanced CO2 conversion with visible light. The solution
      processed self-assembly strategy renders the building of uniform and intimate
      junctions between PCN layers and ZnIn2 S4 subunits, which remarkably accelerates
      the separation and transfer of photogenerated charge carriers. In addition, the
      layered composites can also promote CO2 adsorption and strengthen the visible
      light absorption. Consequently, the optimized PCN/ZnIn2 S4 sheet-shaped composite
      shows reinforced photoactivity for deoxygenative CO2 conversion, affording a high
      CO-production rate of 44.6 MUmol h-1 , which is 223 times higher than that of the
      pristine PCN nanosheets. Moreover, the heterojunction photocatalyst also exhibits
      high stability during repeated runs for five cycles.

PMID- 30091278
TI  - Radial-probe endobronchial ultrasound outcomes in the investigation of peripheral
      pulmonary lesions: a New Zealand perspective.
AB  - BACKGROUND: Radial-probe endobronchial ultrasound (radial-EBUS) is becoming an
      important investigation for peripheral pulmonary lesions (PPL). A key advantage
      of radial-EBUS is the favourable risk profile compared with current gold-standard
      computerised tomography-guided biopsy. AIM: To investigate the diagnostic yield,
      predictors of positive yield and radial-EBUS safety in a New Zealand institution.
      We also determined whether molecular analysis was possible on the same tissue
      samples. METHODS: We performed a retrospective analysis of all patients (n = 68)
      from Middlemore Hospital, Auckland, undergoing radial-EBUS with guide-sheath for
      PPL from March 2015 to August 2016. Clinical, radiological and procedural data
      were collected. Radial-EBUS diagnostic yield was determined for malignant and
      benign diagnoses, and molecular analysis yield was determined on appropriate
      malignant samples. Logistic regression was used to determine factors predicting
      successful radial-EBUS. RESULTS: Overall diagnostic yield of radial-EBUS was
      55.9% (95% confidence interval (CI): 44.3-67.9). Malignant diagnostic sensitivity
      was 60.8% (95% CI: 46.1-74.2) and benign diagnostic sensitivity was 50% (95% CI:
      23-77). Lesions close to the hilum (P = 0.039), concentric radial-probe
      positioning (P = 0.008) and the use of forceps as first instrument (P = 0.0049)
      significantly predicted successful diagnostic yield. Of the malignant cases 81.0%
      (95% CI: 58.1-94.6) were sufficient for molecular analysis. Pneumothorax occurred
      in 4.4% (95% CI: 0.9-12.4), none required chest drain intervention. There were no
      cases of significant pulmonary haemorrhage. CONCLUSION: Radial-EBUS was shown to
      be safe with diagnostic yield similar to international reports. Important
      predictors of success include distance from hilum, probe position and forceps as
      first instrument. We also demonstrated that molecular analysis is possible in
      radial-EBUS obtained samples.

PMID- 30091279
TI  - Chronic pancreatitis correlates with increased risk of herpes zoster in a
      population-based retrospective cohort study.
AB  - BACKGROUND: The association between chronic pancreatitis and herpes zoster has
      not been fully investigated. The objective of the study was to investigate
      whether there is an association between chronic pancreatitis and herpes zoster in
      Taiwan. METHODS: Using the claim data of the Taiwan National Health Insurance
      Program, we identified 1,545 participants aged 20-84 years with a new diagnosis
      of chronic pancreatitis from 2000 to 2012 as the chronic pancreatitis group. We
      selected 6,022 sex-matched and age-matched participants without chronic
      pancreatitis as the non-chronic pancreatitis group. The incidence of herpes
      zoster at the end of 2013 was measured. The multivariable Cox proportional
      hazards regression model was used to measure the hazard ratio (HR) and 95%
      confidence interval (CI) for herpes zoster associated with chronic pancreatitis.
      RESULTS: The overall incidence of herpes zoster was 1.34-fold greater in the
      chronic pancreatitis group than the non-chronic pancreatitis group (6.22 vs. 4.63
      per 1,000 person-years, 95% CI 1.16-1.57). After controlling for confounding
      factors, the adjusted HR of herpes zoster was 1.35 (95% CI 1.01-1.82) for the
      chronic pancreatitis group, compared with the non-chronic pancreatitis group.
      CONCLUSIONS: Chronic pancreatitis correlates with 1.35-fold increased risk of
      herpes zoster. From a view of primary prevention, we suggest that patients with
      chronic pancreatitis should receive herpes zoster vaccination.

PMID- 30091280
TI  - The CONSORT-SPI 2018 extension: a new guideline for reporting social and
      psychological intervention trials.

PMID- 30091281
TI  - Ferrihydrite-Modified Ti-Fe2 O3 as an Effective Photoanode: The Role of Interface
      Interactions in Enhancing the Photocatalytic Activity of Water Oxidation.
AB  - Semiconductor electrodes integrated with cocatalysts are key components of
      photoelectrochemistry (PEC)-based solar-energy conversion. However, efforts to
      optimize the PEC device have been limited by an inadequate understanding of the
      interface interactions between the semiconductor-cocatalyst (sem|cat) and
      cocatalyst-electrolyte (cat|ele) interface. In our work, we used ferrihydrite
      (Fh)-modified Ti-Fe2 O3 as a model to explore the transfer process of
      photogenerated charge carriers between the Ti-Fe2 O3 -Fh (Ti-Fe2 O3 |Fh)
      interface and Fh-electrolyte (Fh|ele) interface. The results demonstrate that the
      biphasic structure (Fh/Ti-Fe2 O3 ) possesses the advantage that the minority hole
      transfer from Ti-Fe2 O3 to Fh is driven by the interfacial electric field at the
      Ti-Fe2 O3 |Fh interface; meanwhile, the holes reached at the surface of Fh can
      rapidly inject into the electrolyte across the Fh|ele interface. As a benefit
      from the improved charge transfer at the Ti-Fe2 O3 |Fh and Fh|ele interface, the
      photocurrent density obtained by Fh/Ti-Fe2 O3 can reach 2.32 mA cm-2 at 1.23 V
      versus RHE, which is three times higher than that of Ti-Fe2 O3 .

PMID- 30091282
TI  - The layered anatomy of the jawline.
AB  - BACKGROUND: To investigate the layered anatomy of the jawline and to provide
      anatomic background for the formation of the labiomandibular sulcus, the jowl
      deformity, and the "double-chin" for safe and effective minimally invasive
      procedures. MATERIALS AND METHODS: Seventy-two fresh-frozen human cephalic
      cadavers (32 males, 40 females; mean age 75.2 +/- 10.9 years, BMI 24.2 +/- 6.6
      kg/m2 , 99% Caucasian ethnicity) were investigated by layer-by-layer anatomical
      dissection. Magnet resonance and computed tomographic imaging was additionally
      carried out to support the anatomical findings. RESULTS: No major neuro-vascular
      structures were found to run in the subdermal plane or in the subcutaneous fat.
      The jowl deformity was identified to be caused by the loose adherence of the
      platysma to the mandible, which occurs posterior (but not anterior) to the
      mandibular ligament. The formation of the submental sulcus was identified to be
      caused by the submental septum, an osteo-cutaneous adhesion spanning all facial
      layers in the submental area. The formation of the labiomandibular sulcus was
      caused by the change in the subcutaneous fibro-connective arrangement rather than
      by an underlying adhesion or ligament. CONCLUSION: The layered arrangement of the
      jawline predisposes this region for subdermal and subcutaneous treatment options
      located superficial to the platysma. Subdermal subcision procedures might have a
      beneficial effect on the labiomandibular sulcus as the boundary between the
      different types of subcutaneous arrangement, which form the sulcus, is being
      smoothened.

PMID- 30091284
TI  - An ocfentanil-related death case: UHPLC-MS/MS analysis of the drug.

PMID- 30091283
TI  - Connection between organizational culture and climate and empowerment: The
      perspective of nurse managers.
AB  - Health-care organizations differ from other institutions due to their unique
      structure and management. Organizational culture and climate are the key
      constructs that compose the organizational social context, and might have an
      impact on employees, such as nurse managers, and the organization itself. The aim
      of this study was to analyze the connections between organizational culture and
      climate and work-related empowerment, and also to present culture and climate
      profiles at team and organization levels. The research was carried out in
      Lithuania among 193 nurse managers in seven hospitals using a questionnaire that
      measured organizational culture and climate (Organizational Social Context
      instrument), and work-related empowerment (Conditions for Work Effectiveness
      Questionnaire-II and Work Empowerment Questionnaire). The findings showed that
      nurse managers were both structurally and psychologically empowered when the
      organizational culture was proficient and resistant, and the climate was engaged
      and functional. These results suggest that nurse managers are more likely to be
      empowered when there is an appropriate organizational culture and climate in the
      workplace. Creating an empowering work environment might have a positive impact
      on individual and organizational outcomes.

PMID- 30091285
TI  - Association between cigarette smoking and diabetes mellitus using two different
      smoking stratifications in 145 040 Korean individuals: Self-reported
      questionnaire and urine cotinine concentrations.
AB  - BACKGROUND: Although previous studies have assessed the relationship between
      smoking and diabetes using self-reported questionnaires, interpretations may be
      limited by an underestimation of the actual smoking population. This study
      evaluated the relationship between smoking and diabetes using both self-reported
      questionnaires and urine cotinine concentrations. METHODS: The present cross
      sectional study enrolled 145 040 Koreans in Kangbuk Samsung Health and Cohort
      Studies between 2011 and 2013. Urinary cotinine was measured after a 10-hour
      smoking-free period. Cotinine-verified current smoking was defined as a urinary
      cotinine concentrations >=50 ng/mL. RESULTS: Overall diabetes prevalence in self
      reported (4.5% vs 1.6%) and cotinine-verified (4.4% vs 2.1%) current smokers was
      higher than in self-reported and cotinine-verified never smokers. Multivariate
      regression analysis showed that cotinine-verified current smoking (odds ratio
      [OR] 1.25; 95% confidence interval [CI] 1.13-1.38), self-reported former smoking
      (OR 1.16; 95% CI 1.01-1.33) and current smoking (OR 1.33; 95% CI 1.17-1.50) were
      associated with increased diabetes compared with cotinine-verified and self
      reported never smoking. Unobserved smoking (OR 1.79; 95% CI 1.20, 2.66) also
      increased the odds for diabetes. There were no significant sex interactions in
      the analyses. CONCLUSIONS: This study shows that self-reported former and current
      smoking, cotinine-verified current smoking, and unobserved smoking (i.e. self
      reported never smoking with urine cotinine >50 ng/mL) are all associated with
      increased diabetes prevalence. These findings suggest that cotinine could provide
      additional information when assessing cardiometabolic risks, such as diabetes.

PMID- 30091286
TI  - Two colorimetric fluorescent turn-on chemosensors for detection of Al3+ and N3 -
      : Synthesis, photophysical and computational studies.
AB  - Two new rhodamine derivative L1 and L2 bearing 2-methoxy-1-naphthaldehyde and 5
      bromo-3-methoxy salicylaldehyde units were designed and synthesized using
      microwave-assisted organic synthesis and utilized towards sequential fluorescence
      detection of aluminum ion (Al3+ ) and azide (N3 - ) in aqueous acetonitrile
      solution. Aluminum ion (Al3+ ) triggers the formation of highly fluorescent ring
      open spirolactam. The fluorescence and colorimetric response of the L1 -Al3+ and
      L2 -Al3+ complexes were quenched by the addition of N3 - , which extracting the
      Al3+ from the complexes and turn-off the sensors, confirming that the recognition
      process is reversible. The recognition ability of the sensors was investigated by
      fluorescence titration, Job's plot, 1 H-NMR spectroscopy and density functional
      theory (DFT) calculations.

PMID- 30091287
TI  - Relationship of cigarette smoking and alcohol consumption to incidence of
      systemic lupus erythematosus in the Black Women's Health Study.
AB  - OBJECTIVE: Systemic lupus erythematosus (SLE) affects Black women more frequently
      than other racial-gender groups. In past studies, largely of Whites and Asians,
      cigarette smoking was associated with increased SLE risk and moderate alcohol
      consumption with decreased SLE risk. We used data from a long-term, prospective
      follow-up study to assess associations of smoking and alcohol consumption with
      risk of incident SLE among Black women. METHODS: The Black Women's Health Study
      enrolled 59,000 Black women in 1995 and collected data on demographics, health
      status, and medical and lifestyle variables. Follow-up questionnaires every two
      years identified incident disease and updated risk factors. We confirmed incident
      SLE meeting American College of Rheumatology 1997 criteria through medical record
      review. We used Cox regression models to estimate hazard ratios (HRs) and 95%
      confidence intervals (CI) for associations of cigarette smoking and alcohol
      intake with incidence of SLE. RESULTS: We confirmed 127 incident SLE cases during
      1995-2015 (mean age 43 at diagnosis). Compared to never smokers, the risk of SLE
      among ever smokers was elevated but not significantly (HR = 1.45, 95% CI 0.97
      2.18). Risk was similar for current and past smoking and increased non
      significantly with increasing pack-years. The HR was 0.71 (95% CI 0.45-1.12), for
      current drinking relative to never drinking, with a HR of 0.43 (95% CI 0.19-0.96)
      for >=4 drinks/week. CONCLUSION: Findings from this first large study among Black
      women are consistent with previous findings in other populations of increased
      risk of SLE associated with cigarette smoking and decreased risk with moderate
      alcohol consumption. This article is protected by copyright. All rights reserved.

PMID- 30091288
TI  - High temperatures change the perspective: integrating hormonal responses in
      citrus plants under co-occurring abiotic stress conditions.
AB  - Plants growing in the field are subjected to multiple stress factors acting
      simultaneously. Abnormally high temperatures are expected to affect wild plants
      and crops in the next years due to global warming. In this work, we have studied
      physiological, hormonal and molecular responses of the citrus rootstock, Carrizo
      citrange (Poncirus trifoliata L. Raf. * Citrus sinensis L. Osb.) subjected to
      wounding or high salinity occurring individually or in combination with heat
      stress. According to our results, combination of high salinity and heat stress
      aggravated the negative effects of salt intoxication in Carrizo. The high
      transpiration rate caused by high temperatures counteracted physiological
      responses of plants to salt stress and increased Cl- intake in leaves. In
      addition, 12-oxo-phytodienoic acid accumulated specifically under combination of
      wounding and heat stress, whereas at low temperatures, wounded plants accumulated
      jasmonic acid (JA) and JA-isoleucine (JA-Ile). Moreover, an antagonism between
      salicylic acid (SA) and JA was observed, and wounded plants subjected to high
      temperatures did not accumulate JA nor JA-Ile whereas SA levels increased (via
      isochorismate synthase biosynthetic pathway). Wounded plants did not accumulate
      abscisic acid (ABA) but its catabolite phaseic acid. This could act as a signal
      for the upregulation of (ABA)-RESPONSIVE ELEMENT (ABRE)-BINDING TRANSCRIPTION
      FACTOR 2 (CsAREB2) and RESPONSIVE TO DISSECATION 22 (CsRD22) in an ABA
      independent way. This work uncovers some mechanisms that explain Carrizo citrange
      tolerance to high temperatures together with different hormonal signals in
      response to specific stresses. It is suggested that co-occurring abiotic stress
      conditions can modify (either enhance or reduce) the hormonal response to
      modulate specific responses.

PMID- 30091289
TI  - Functional characterization of the extranasal OR2A4/7 expressed in human
      melanocytes.
AB  - Olfactory receptors (ORs) were first described as specialized chemoreceptors in
      the nasal epithelium. In the last two decades, ORs have also been detected to be
      functionally expressed and active in different nonolfactory tissues of the human
      body, because they used to react to specific odour stimuli. In this study, we
      conducted a characterization of the extranasal OR2A4/7 expressed in primary human
      melanocytes and sections of the human skin. OR2A4/7 expression could be
      demonstrated at the transcript and protein level. We uncovered elevated
      intracellular cAMP and Ca2+ levels accompanied by elevated p38 and reduced p42/44
      MAPK phosphorylation following odourant (cyclohexyl salicylate; CHS) stimulation
      of melanocytes. These results were associated with enhanced melanin biosynthesis
      in conjunction with the growth inhibition and differentiation of melanocytes. Our
      findings highlight the participation of OR2A4/7 in human primary melanocyte
      physiology and suggest an alternate mechanism that regulates melanogenesis.

PMID- 30091290
TI  - Applications of Human Brain Organoids to Clinical Problems.
AB  - Brain organoids are an exciting new technology with the potential to
      significantly change how diseases of the brain are understood and treated. These
      three-dimensional neural tissues are derived from the self-organization of
      pluripotent stem cells, and they recapitulate the developmental process of the
      human brain, including progenitor zones and rudimentary cortical layers. Brain
      organoids have been valuable in investigating different aspects of developmental
      neurobiology and comparative biology. Several characteristics of organoids also
      make them attractive as models of brain disorders. Data generated from human
      organoids are more generalizable to patients because of the match in species
      background. Personalized organoids also can be generated from patient-derived
      induced pluripotent stem cells. Furthermore, the three-dimensionality of brain
      organoids supports cellular, mechanical, and topographical cues that are lacking
      in planar systems. In this review, we discuss the translational potential of
      brain organoids, using the examples of Zika virus, autism-spectrum disorder, and
      glioblastoma multiforme to consider how they could contribute to disease
      modeling, personalized medicine, and testing of therapeutics. We then discuss
      areas of improvement in organoid technology that will enhance the translational
      potential of brain organoids, as well as the possibility of their use as
      substrates for repairing cerebral circuitry after injury.

PMID- 30091291
TI  - Cells in the adult human spinal cord ependymal region do not proliferate after
      injury.
AB  - In vertebrates that regenerate the injured spinal cord, cells at the ependymal
      region proliferate and coordinate the formation of bridges between the lesion
      stumps. In mammals, these cells also proliferate profusely around the central
      canal after spinal cord injury, although their actual contribution to repair is
      controversial. In humans, however, the central canal disappears from early
      childhood in the majority of individuals, being replaced by astrocyte gliosis,
      ependymocyte clusters, and perivascular pseudo-rosettes. In this human ependymal
      remnant, cells do not proliferate under normal conditions, but it is not known if
      they do after a lesion. Here, we studied the human ependymal remnant after
      traumatic spinal cord injury using samples from 21 individuals with survival
      times ranging from days to months post-injury. With three different monoclonal
      antibodies raised against two different proliferation markers (Ki67 and MCM2), we
      found that the ependymal remnant in adult humans does not proliferate after
      injury at any time or distance from the lesion. Our results seriously challenge
      the view of the spinal cord ependymal region as a neurogenic niche in adult
      humans and suggest that it would not be involved in cell replacement after a
      lesion. Copyright (c) 2018 Pathological Society of Great Britain and Ireland.
      Published by John Wiley & Sons, Ltd.

PMID- 30091292
TI  - MAP4 regulates Tctex-1 and promotes the migration of epidermal cells in hypoxia.
AB  - After acute wound formation, the oxygen supply is reduced, which results in the
      formation of an acute hypoxic microenvironment; whether this hypoxic
      microenvironment enhances epidermal cell migration and the underlying regulatory
      molecular mechanism of this effect are unclear. In this study, HaCaT cells were
      maintained under hypoxic (1% oxygen) or normoxic conditions. Methods including
      immunofluorescence staining, wound scratch assays, transwell assays, Western
      blotting and high- and low-expression lentiviral vector transfection were
      utilized to observe the changes in cell migration, microtubule dynamics and the
      expression levels of microtubule-associated protein (MAP) 4 and the light chain
      protein DYNLT1 (Tctex-1). The possible mechanisms were studied and discussed. The
      results showed that epidermal cell migration was enhanced during early hypoxia.
      Further experiments revealed that MAP4 regulates microtubule dynamics and
      promotes epidermal cell migration through Tctex-1. MAP4 and Tctex-1 play
      important roles in regulating the migration of epidermal cells under hypoxia.
      This evidence will provide a basis for further revealing the cellular and
      molecular mechanisms of local wound hypoxia and for promoting wound healing.

PMID- 30091293
TI  - Inequality of opportunity in health: A decomposition-based approach.
AB  - This paper presents new decomposition-based approaches to measure inequality of
      opportunity in health that capture Roemer's distinction between circumstances and
      effort and are consistent with both compensation and reward principles. Our
      approach is fully nonparametric in the way that it handles differences in
      circumstances and provides decompositions of both a rank-dependent relative (the
      Gini coefficient) and a rank-independent absolute inequality index (the
      variance). The decompositions distinguish the contribution of effort from the
      direct and indirect (through effort) contribution of circumstances to the total
      inequality. Our approach is illustrated by an empirical application that uses
      objectively measured biomarkers as health outcomes and as proxies for relevant
      effort variables. Using data from the Health Survey for England from 2003 to
      2012, we find that circumstances are the leading determinant of inequality in
      cholesterol, glycated haemoglobin, and in a combined ill-health index whereas
      effort plays a substantial role in explaining inequality in fibrinogen only.

PMID- 30091294
TI  - Hospital discharge data under-reports delirium occurrence. Results from a point
      prevalence survey of delirium in a major Australian health service.
AB  - BACKGROUND: Delirium in hospitalised patients is common, and a risk factor for
      adverse outcomes. Health services require accurate delirium data to monitor the
      impact of initiatives designed to improve detection and prevention of delirium.
      AIM: To determine the extent to which ICD codes represent delirium occurrence.
      METHODS: A cross-sectional point prevalence survey was used to audit delirium
      occurrence in 25 inpatient wards of an Australian health service. All adult
      patients were eligible. Exclusion was for coma, end-of-life, or behaviour that
      posed a risk to delirium assessors. Specially-trained nurses and allied health
      professionals screened patients for any cognitive impairment using the 4 A's
      Test. Those with abnormal screen test results were assessed using the '3-Minute
      Diagnostic Interview for the Confusion Assessment Method' (3D-CAM). Delirium
      detected by 3D-CAM was the reference standard. RESULTS: Of potentially eligible
      patients, 559/667 (83.8%) were assessed. The mean age was 73 years (+/-16.4),
      54.5% were female, and 43.8% (245/559) had cognitive impairment (4AT score >=1).
      The occurrence of delirium during hospitalisation as identified by ICD codes was
      10.4% (58/559; 95% CI, 7.9-12.7) compared with a point prevalence of 16.2%
      (91/559; 95% CI, 13.2-19.1). Just 31/91 (34.1%) of those with delirium had ICD
      delirium codes assigned. CONCLUSIONS: ICD coding is inadequate to determine in
      hospital delirium incidence. Instead, a point prevalence detection of delirium
      using the methods described above could be used. Health services could apply the
      described survey method to evaluate their local initiatives for the improvement
      of delirium detection and prevention. This article is protected by copyright. All
      rights reserved.

PMID- 30091295
TI  - Hospitalisation rates and characteristics for adult and childhood IgA vasculitis
      in Western Australia.
AB  - OBJECTIVES: Immunoglobulin A vasculitis (IgAV) is a systemic small-vessel
      vasculitis of unknown aetiology. Although commonest in children, onset in
      adulthood is not unusual. As Australian data are lacking, we investigated
      longitudinal hospitalisation rates and characteristics for both adult and
      paediatric IgAV patients in Western Australia (WA). METHODS: Data was extracted
      from a state-wide register for all first hospital contacts in WA between 1980 and
      2015 for patients with a primary diagnosis of IgAV. Paediatric cases were defined
      as those <20 years and compared with adult cases for admission rates per 100,000,
      demographics, complications, length of stay (LOS) and readmission rates. RESULTS:
      The study cohort included 476 children (median age 5 years (yrs.) (IQR 3-7) and
      144 adults (median age 50 yrs. (IQR 36-77). Childhood admission rates declined
      from 3.85 to 0.31 over time (p<0.001) but age at admission and LOS remained
      unchanged. For adults, admission rates declined from 0.40 to 0.17 (p=0.02) while
      age at admission (43 vs. 63 yrs., p=0.01) and LOS (5 vs. 9 days, p=0.02)
      increased. More adults had renal (11.8% vs. 1.3%, p<0.01), intestinal (3.5% vs.
      0.8%, p=0.04) and infectious (14.6% vs. 5.3%, p<0.01) complications. Readmission
      was more frequent in childhood cases (23.1% vs. 7.6%, p<0.05) occurring mostly
      within 30 days of discharge. CONCLUSIONS: Hospitalisation rates for adults with
      IgAV now nearly equal those in children as adult IgAV leads to more complications
      .The sharp decline in childhood IgAV admissions suggests that confidence to
      manage children with IgAV outside the hospital setting has increased. This
      article is protected by copyright. All rights reserved.

PMID- 30091296
TI  - Impact of Non-Malignant Portal Vein Thrombosis in Transplant Recipients with
      Nonalcoholic Steatohepatitis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition
      and its more severe progressive state, nonalcoholic steatohepatitis (NASH), is
      currently the second most common indication for waitlisted adults in the United
      States. The association of portal vein thrombosis (PVT) prior to or at transplant
      and poor graft and patient outcomes is not well established, particularly among
      NASH patients who inherently have an increased hypercoagulable profile. Using the
      United Network for Organ Sharing dataset, we analyzed graft and patient outcomes
      of patients transplanted for the indication of NASH with and without PVT. Of
      3,689 NASH transplant recipients, the prevalence of PVT was 12% (450 with PVT and
      3,239 without PVT). NASH transplant recipients with PVT had inferior graft and
      patient survival compared to NASH transplant recipients without PVT, even after
      adjusting for recipient and donor demographic characteristics, body mass index
      (BMI), synthetic dysfunction, and presence of diabetes. In a multivariate Cox
      regression model, NASH transplant recipients with PVT had a 37% increased risk of
      graft failure (hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.15-1.63;
      P < 0.001) and 31% increased risk of overall death (HR, 1.31; 95% CI, 1.09-1.58;
      P < 0.001) compared with NASH transplant recipients without PVT at transplant.
      This difference in graft and patient survival was most pronounced in the early
      post-transplant period. These results demonstrate NASH patients with PVT have
      decreased graft and patient survival independent of recipient and donor factors.
      This article is protected by copyright. All rights reserved.

PMID- 30091297
TI  - Serological evidence of duck Tembusu virus infection in free-grazing ducks,
      Thailand.
AB  - Duck Tembusu virus (DTMUV) has been reported in ducks raised in farming system
      since its emergence in 2010. No information is available on DTMUV infection in
      free-grazing ducks, which are commonly raised and widespread in several Asian
      countries. To determine the presence of DTMUV infection in free-grazing ducks in
      Thailand, retrospective serum samples collected from 1,000 free-grazing ducks
      during 2008-2015 were tested for DTMUV infection. Our result showed that 91
      (9.10%) were positive for DTMUV neutralizing antibodies and DTMUV seropositive
      ducks have been detected in Thailand since 2008. To further investigate the
      seroprevalence and geographic distribution of DTMUV infection in free-grazing
      ducks in Thailand, a cross-sectional serological survey of DTMUV was conducted in
      2016. Of 1,200 free-grazing ducks in the 60 flocks from 20 provinces located in
      the major free-grazing duck raising areas of Thailand, 365 (30.42%) were positive
      for DTMUV neutralizing antibodies and 56 flocks (93.33%) had at least one DTMUV
      seropositive duck. Additionally, DTMUV seropositive ducks were observed in all
      provinces tested. In conclusion, our data demonstrated the presence of DTMUV
      infection in free-grazing ducks since 2008 and widespread DTMUV infection in free
      grazing ducks in Thailand with a relatively high seroprevalence. These findings
      suggest the potential role of free-grazing ducks in the dissemination of DTMUV
      and highlight the necessity of systemic DTMUV surveillance in free-grazing ducks
      in addition to farm ducks for early detection, prevention, and control of this
      emerging disease.

PMID- 30091298
TI  - The effect of dream report collection and dream incorporation on memory
      consolidation during sleep.
AB  - Collecting dream reports typically requires waking subjects up from their sleep-a
      method that has been used to study the relationship between dreams and memory
      consolidation. However, it is unclear whether these awakenings influence sleep
      associated memory consolidation processes. Furthermore, it is unclear how the
      incorporation of the learning task into dreams is related to memory
      consolidation. In this study we compared memory performance in a word-picture
      association learning task after a night with and without awakenings in 22 young
      and healthy participants. We then examined if the stimuli from the learning task
      are successfully incorporated into dreams, and if this incorporation is related
      to the task performance the next morning. We show that while the awakenings
      impaired both subjective and objective sleep quality, they did not affect sleep
      associated memory consolidation. When dreams were collected during the night by
      awakenings, memories of the learning task were successfully incorporated into
      dreams. When dreams were collected in the morning, no incorporations were
      detected. Task incorporation into non-rapid eye movement sleep dreams, but not
      rapid eye movement sleep dreams positively predicted memory performance the next
      morning. We conclude that the method of awakenings to collect dream reports is
      suitable and necessary for dream and memory studies. Furthermore, our study
      suggests that dreams in non-rapid eye movement rather than rapid eye movement
      sleep might be related to processes of memory consolidation during sleep.

PMID- 30091299
TI  - Energy-Efficient Nitrogen Reduction to Ammonia at Low Overpotential in Aqueous
      Electrolyte under Ambient Conditions.
AB  - The electrochemical nitrogen reduction reaction (NRR) under ambient conditions is
      a promising alternative to the traditional energy-intensive Haber-Bosch process
      to produce NH3 . The challenge is to achieve a sufficient energy efficiency,
      yield rate, and selectivity to make the process practical. Here, we demonstrate
      that Ru nanoparticles (NPs) enable NRR in 0.01 m HCl aqueous solution at very
      high energy efficiency, that is, very low overpotentials. Remarkably, the NRR
      occurs at a potential close to or even above the H+ /H2 reversible potential,
      significantly enhancing the NRR selectivity versus the production of H2 . NH3
      yield rates as high as ~5.5 mg h-1  m-2 at 20  degrees C and 21.4 mg h-1  m-2 at
      60  degrees C were achieved at a redox potential (E) of -100 mV versus the
      reversible hydrogen electrode (RHE), whereas a highest Faradaic efficiency (FE)
      of ~5.4 % is achievable at E=+10 mV vs. RHE. This work demonstrates the potential
      use of Ru NPs as an efficient catalyst for NRR at ambient conditions. This
      ability to catalyze NRR at potentials near or above RHE is imperative in
      improving the NRR selectivity towards a practical process as well as rendering
      the H2 viable as byproduct. Density functional theory calculations of the
      mechanism suggest that the efficient NRR process occurring on these predominantly
      Ru (0 0 1) surfaces is catalyzed by a dissociative mechanism.

PMID- 30091300
TI  - Measurements of tension on wound edges after strip harvest surgery.
AB  - OBJECTIVE: To measure the wound closure tension after strip surgery. MATERIALS
      AND METHODS: The study was conducted in a private setup on patients undergoing
      first hair restoration surgery. The donor strip was marked with the patient in
      sitting position after checking the vertical scalp mobility. Six stitches of
      nonabsorbable suture were passed through the intact skin with a loop of 3-4 cm;
      two stitches were passed in the midline and two on either side. The end of the
      digital scale was passed through the loop. The scales were then pulled in the
      opposite direction to measure the tension. The tension was measured at all three
      points, that is, A, B, & C. The data were collected and reviewed statistically.
      RESULTS: A total of 20 patients were included in the study. The mean age of the
      patients was 33.05 years. The mean wound closure tension in the midline (point A
      & A') was 2.3115 lb-f (range 0.30-3.69), whereas the tension at point B & B' was
      2.562 lb-f (range 0.36-4.03) and 2.6345 lb-f (range 0.51-4.71) at C & C',
      respectively. The average tension after removal of 10-mm strip was 0.90 lb-f. The
      removal of 11-mm-wide strip resulted in 2.693 lb-f, 12 mm removal had 2.445 lb-f,
      13 mm removal had 2.545 lb-f, 14 mm removal had 2.701 lb-f, and 15 mm removal had
      3.063 lb-f average. CONCLUSION: Measurement of wound closure tension is important
      to be kept minimal in order to obtain a good scar.

PMID- 30091301
TI  - Effect of obstructive sleep apnea and its treatment of atrial fibrillation
      recurrence after radiofrequency catheter ablation: A meta-analysis.
AB  - BACKGROUND/OBJECTIVES: Patients with obstructive sleep apnea (OSA) have an
      increased the risk of developing atrial fibrillation (AF). However, it remains
      unclear if patients with OSA carry a higher risk of recurrent AF after successful
      catheter ablation. This meta-analysis was conducted (1) to evaluate the
      association between OSA and recurrent AF after catheter ablation, and (2) to
      assess the effect of continuous positive airway pressure (CPAP) on the risk of
      recurrent AF in patients with OSA. METHODS: A comprehensive literature review was
      conducted using MEDLINE, EMBASE, Cochrane databases from inception through July
      2017 to identify studies that evaluated the risk of recurrent AF after successful
      catheter ablation in patients with OSA were included. Effect estimates from the
      individual study were extracted and combined using random-effect, generic inverse
      variance method of DerSimonian and Laird. RESULTS: Seven observational studies
      with a total of 4572 patients AF after successful catheter ablation were
      enrolled. Compared to patients without OSA, the pooled OR of recurrent AF in
      patients with OSA was 1.70 (95% CI, 1.40-2.06, I2  = 0). Among OSA patients with
      AF after successful catheter ablation, the use of CPAP was significantly
      associated with decreased risk of recurrent AF with pooled OR of 0.28 (0.19-0.40,
      I2  = 0). Egger's regression asymmetry test was performed and showed no
      publication bias for the associations of OSA and CPAP with recurrent AF.
      CONCLUSIONS: Our meta-analysis suggested a significant association between OSA
      and recurrent AF after catheter ablation. The use of CPAP in patients with OSA is
      associated with reduced risk of recurrent AF after catheter ablation.

PMID- 30091302
TI  - Clinical and Demographic Characteristics of Blepharoptosis in Korea: A 24-year
      Experience including 2,328 Patients.
AB  - PURPOSE: To describe the demographics, relative incidence of subtypes, and
      clinical characteristics of blepharoptosis in Korean patients. METHODS: This is a
      retrospective, observational case series consisting of 2,328 patients who
      underwent ptosis surgery from 1991 to 2014 at a tertiary referral hospital in
      Korea. The patients were classified according to the type of ptosis and the
      evaluation of clinical characteristics including levator muscle function (LF) and
      degree of ptosis. RESULTS: Of the 2,328 patients, 1,815 (78%) had congenital
      ptosis and 513 (22%) had acquired ptosis. Simple congenital ptosis is the most
      common type overall (73.7%), and aponeurotic ptosis is the most common acquired
      type. More than three-quarters of eyes with congenital ptosis were affected in a
      moderate (34.4%) to severe degree (41.3%), and most of these eyes had fair
      (33.7%) to poor LF (60.1%). Among eyes with acquired ptosis, approximately three
      quarters were affected in a mild (33.3%) to moderate degree (41.0%), with 63.3%
      of these eyes having good LF. The most widely used surgical technique was
      frontalis suspension (55.1%), followed by levator resection (29.0%) and
      aponeurosis repair (14.8%). At 3 years after the first surgery, 15.7% of patients
      with congenital ptosis and 10.4% of patients with acquired ptosis underwent
      reoperation. CONCLUSIONS: Although the prevalence has decreased from previous
      years, the proportion of cases with congenital ptosis was higher in this study
      than has been shown in research conducted in the West. The majority of eyes with
      congenital ptosis was affected to a severe degree and had poor LF, while those
      with acquired ptosis were affected to a moderate degree and had good LF. More
      cases with acquired ptosis presented with fair to poor LF, and frontalis
      suspension surgery was performed more commonly compared to previous studies. The
      reoperation rate was higher in congenital ptosis compared to acquired ptosis.

PMID- 30091303
TI  - Comparison of Ocular Biometry Using New Swept-source Optical Coherence Tomography
      based Optical Biometer with Other Devices.
AB  - PURPOSE: To evaluate the agreement between optical biometry with swept-source
      optical coherence tomography-based optical biometry (IOLMaster 700) and other
      devices. METHODS: A total of 137 eyes (78 patients) with cataracts were included
      in this retrospective study. Axial length (AL), anterior chamber depth (ACD),
      keratometry, and white-to-white (WTW) distance measured using IOLMaster 700 were
      compared with results for the following five different biometers: IOLMaster 500,
      A-scan, automated refractor, manual keratometry, and Galilei G4. Differences and
      correlations among the devices were assessed using the Bland-Altman plot and
      intraclass correlation coefficient (ICC). RESULTS: For AL values, the IOLMaster
      700, IOLMaster 500, and A-scan measurements showed excellent agreement (all ICC
      >0.99). For ACD values, ICC of IOLMaster 700 and Galilei G4 was 0.965 but A-scan
      was poorly correlated with either IOLMaster 700 or Galilei G4. The ICCs of
      IOLMaster 700 and other devices were all greater than 0.9 for average
      keratometry, but those of the mean cylinder keratometry were all between 0.7 and
      0.8. The mean difference in the WTW distance between the IOLMaster 700 and
      Galilei G4 was 0.029 mm, but the ICC was 0.525. AL measurements were not possible
      for 10 eyes with the IOLMaster 500 but were obtained in all eyes with the
      IOLMaster 700. CONCLUSIONS: In clinical practice, AL, ACD, and average
      keratometry values of IOLMaster 700 can be used interchangeably with those of the
      other devices tested. However, the ACD value between IOLMaster 700 and A-scan or
      the WTW distance between IOLMaster 700 and Galilei G4 are not interchangeable
      because of clinical and statistical differences in measurements between the
      devices.

PMID- 30091304
TI  - Improving the Toric Intraocular Lens Calculation by Considering Posterior Corneal
      Astigmatism and Surgically-induced Corneal Astigmatism.
AB  - PURPOSE: To investigate the effect of surgically induced corneal astigmatism
      (SICA) and total corneal astigmatism (TCA) estimation on the anterior corneal
      astigmatism (ACA)-based toric intraocular lens (IOL) calculation. METHODS: Data
      from preoperative and postoperative corneal astigmatism, postoperative visual
      acuities, and refractive outcomes were collected. The incision was superior in
      with the rule anterior corneal astigmatism (WTRA) eyes and temporal in against
      the rule anterior corneal astigmatism eyes. The following five methods of
      calculating the toric IOL were compared: (1) ACA only and estimated SICA; (2) ACA
      with a fixed posterior corneal astigmatism (PCA) and estimated SICA; (3) ACA with
      a fixed PCA value and actual SICA; (4) and (5) TCA derived from the regression
      equations of ACA and actual SICA. The residual astigmatism was simulated. The
      Alpins method was used to analyze the astigmatism. RESULTS: Sixty eyes from 46
      patients were enrolled. Thirty eyes had WTRA and the other thirty had against the
      rule anterior corneal astigmatism. The vector and arithmetic means of the
      difference vector decreased when the information regarding the actual SICA and
      PCA was added to the calculation (from 0.59 diopters [D] @ 87.5 degrees  to 0.15
      D @ 48.5 degrees , and from 0.95 +/- 0.53 to 0.71 +/- 0.63 D, respectively; p <
      0.001). The mean difference vector across the whole sample was lowest using model
      5. The correction index was significantly closest to 1.0 in the WTRA group.
      CONCLUSIONS: Researchers may improve the accuracy of post-implantation
      predictions by calculating toric IOL using exact SICA and TCA, with consideration
      of the PCA derived from the regression equation of ACA.

PMID- 30091305
TI  - Predicting Factor of Visual Outcome in Unilateral Idiopathic Cataract Surgery in
      Patients Aged 3 to 10 Years.
AB  - PURPOSE: To report the surgical results of unilateral pediatric cataracts from
      uncertain causes in relatively older children and to identify factors related to
      better visual outcomes. METHODS: We retrospectively evaluated the medical records
      of 39 patients who underwent surgery between the ages of 3 and 10 years for
      unilateral pediatric cataracts of no known cause. All patients underwent primary
      intraocular lens implantation and postoperative amblyopia treatment. A
      postoperative final visual acuity better than 20 / 30 was considered to be a good
      visual outcome. RESULTS: The mean age of patients was 6.0 +/- 1.8 years at the
      time of surgery. The mean preoperative visual acuity was 1.07 +/- 0.71 logarithm
      of the minimum angle of resolution (range, 0.15 to 3.00), while the mean final
      postoperative visual acuity was 0.47 +/- 0.54 logarithm of the minimum angle of
      resolution (range, 0.00 to 2.00). Of 39 patients, 18 (46.2%) achieved a good
      visual outcome. Only the preoperative visual acuity maintained a significant
      association with a good visual outcome according to our multivariate analysis (p
      = 0.040). A preoperative visual acuity of 20 / 100 or better was found to
      increase the chance of achieving a good visual outcome by 13.79-fold (95%
      confidence interval, 1.13 to 167.58). CONCLUSIONS: The visual outcome of
      unilateral pediatric cataract surgery for cataracts with no specific cause
      identified in patients after three years of age could be satisfactory, especially
      with a preoperative visual acuity of 20 / 100 or better.

PMID- 30091306
TI  - Association of Central Serous Chorioretinopathy with Psychosocial Factors is
      Dependent on Its Phase and Subtype.
AB  - PURPOSE: To analyze the psychosocial factors associated with central serous
      chorioretinopathy (CSC) according to its phases and subtypes and to correlate the
      factors with the extent of choroidal hyperpermeability. METHODS: Age- and sex
      matched CSC patients and controls (n = 37 in each group) were enrolled, and their
      psychosocial factors were compared. CSC was divided into two phases (active and
      inactive), and active CSC was further divided into two subtypes (acute and
      chronic). The correlations between the size of the hyperpermeable choroidal
      lesion identified on indocyanine green angiography and psychosocial factors were
      examined. RESULTS: Active CSC patients experienced more stressful events (p =
      0.030), were more depressive (p = 0.037), and felt less emotional (p = 0.014) and
      informational (p = 0.014) support than the matched controls, whereas inactive CSC
      patients were comparable to the matched controls in all psychosocial factors.
      Among the active CSC patients, acute patients were more depressive (p = 0.029),
      while chronic patients experienced more stressful events (p = 0.024) than their
      matched controls. The size of the hyperpermeable choroidal lesion was correlated
      with the severity of depression in acute patients. CONCLUSIONS: Association of
      CSC with psychosocial factors was dependent on the phase and subtype of CSC.
      Psychosocial factors were associated with CSC in the active phase, and severity
      of depression was correlated with the size of the choroidal pathology in acute
      active CSC. Further prospective studies to investigate if psychosocial factors
      can trigger CSC are warranted.

PMID- 30091307
TI  - Choroidal Thickness Indicates Subclinical Ocular and Systemic Inflammation in
      Eyes with Behcet Disease without Active Inflammation.
AB  - PURPOSE: To investigate whether subfoveal choroidal thickness, measured using
      enhanced depth imaging optical coherence tomography (EDI-OCT), is an indicator of
      subclinical ocular or systemic inflammation in eyes with Behcet disease (BD)
      without active ocular inflammation. METHODS: A retrospective analysis was used to
      examine clinical features of non-uveitic patients with BD (NUBD group), patients
      with a previous history of Behcet uveitis in an inactive state (IUBD group), and
      healthy controls were evaluated from October 2014 to September 2015. Subfoveal
      choroidal thickness was measured using EDI-OCT. RESULTS: The NUBD group included
      46 eyes in 24 patients; the IUBD group included 16 eyes in 11 patients; and the
      control group included 35 eyes in 23 individuals. The mean subfoveal choroidal
      thicknesses differed significantly among these groups. Choroidal thickness was
      significantly greater in the NUBD (310.5 +/- 81.0 MUm) than in the IUBD (263.1 +/
      56.6 MUm, p = 0.013) and control (256.9 +/- 67.9 MUm, p = 0.002) groups. The
      disease activity score was significantly higher in the NUBD than in the IUBD
      group (p < 0.001), while the use of cyclosporine was significantly associated
      with choroidal thickness in eyes with NUBD (p = 0.039). CONCLUSIONS: Subfoveal
      choroidal thickness, as measured by EDI-OCT, may be a clinical indicator of
      subclinical ocular inflammation and systemic inflammation in BD patients without
      active ocular inflammation.

PMID- 30091308
TI  - Effectiveness of Intravitreal Ranibizumab for Diabetic Macular Edema with Serous
      Retinal Detachment.
AB  - PURPOSE: To evaluate the effectiveness of intravitreal injection of ranibizumab
      (IVR) in treating diabetic macular edema (DME) with serous retinal detachment
      (SRD) based on spectral domain optical coherence tomography (SD-OCT) patterns.
      METHODS: One hundred thirty-four eyes of 134 patients with DME who underwent SD
      OCT evaluation were included in this study. We retrospectively analyzed the
      medical records of patients who received IVR for the treatment of DME. Their eyes
      were classified into three groups according to the following SD-OCT features:
      SRD, diffuse retinal thickness and cystoid macular edema. The three groups were
      compared regarding changes in best-corrected visual acuity and central foveal
      thickness (CFT) after IVR. RESULTS: The mean age was 61.4 +/- 9.2 years (range,
      44 to 81 years). The average length of the follow-up period was 9.4 +/- 3.4
      months (range, 6 to 24 months). The mean CFT value was significantly reduced in
      all groups (p < 0.001) after treatment. Increases in best-corrected visual acuity
      were statistically significant for the diffuse retinal thickness and cystoid
      macular edema groups (p < 0.001 and p < 0.001, respectively). However, there was
      no significant improvement after IVR injection in the SRD group (p = 0.252). In
      the SRD group, patients with ellipsoid zone disruption and external limiting
      membrane disruption demonstrated poorer visual gains at the last follow-up visit
      (p < 0.005 and p = 0.002, respectively). CONCLUSIONS: A significant reduction in
      CFT with required IVR injections in DME with SRD was achieved but was accompanied
      by a worse functional outcome in the SRD group. The presence of subretinal fluid
      on SD-OCT in study eyes may be a poor prognostic factor for visual acuity.

PMID- 30091309
TI  - Optical Coherence Tomography Measurement and Visual Outcome in Acute Central
      Retinal Artery Occlusion.
AB  - PURPOSE: This study investigated visual acuity (VA) values and differences
      depending on optical coherence tomography (OCT) findings in patients with acute
      central retinal artery occlusion (CRAO). METHODS: A retrospective chart review
      was performed on patients with acute CRAO who underwent macular and disc OCT. We
      evaluated changes in macular thickness and retinal nerve fiber layer (RNFL)
      thickness after acute CRAO onset based on OCT. We also determined the association
      of thickness changes with VA improvement. RESULTS: This study involved both eyes
      in a total of 12 patients with acute CRAO. A significant increase was observed in
      foveal (1 mm) thickness (p = 0.002), parafoveal (3 mm) thickness (p = 0.002), and
      peripapillary RNFL thickness (p = 0.005) in affected eyes with CRAO, but not in
      central foveal thickness (p = 0.266). A significant small difference in both eyes
      (affected eye - fellow eye) was shown in foveal (1 mm) and mean parafoveal (3 mm)
      thickness in the improved VA group (p = 0.008 and p = 0.004, respectively), but
      not in central foveal or peripapillary RNFL thickness (both p = 0.283).
      CONCLUSIONS: Both macular and RNFL thickness increased in patients with acute
      CRAO. RNFL thickness decreased over time with progression of RNFL atrophy. Less
      macular damage caused by acute CRAO could be predicted by a small difference in
      macular thickness between eyes (affected eye - fellow eye). In such cases,
      patients had a greater chance of VA improvement.

PMID- 30091310
TI  - Macular Thickness in Moderate to Severe Amblyopia.
AB  - PURPOSE: To compare the macular retinal thickness of moderately to severely
      amblyopic eyes with non-amblyopic eyes as controls. METHODS: This case control
      study was conducted on 56 children aged 4 to 10 years old (64.3% female
      subjects). Twenty-eight children had unilateral amblyopia (28 amblyopic eyes as
      cases and 28 normal fellow eyes as internal controls) and 28 children had normal
      visual acuity in both eyes and were considered as external controls (n = 56
      eyes). Among our cases, 14 had strabismic amblyopia and 14 had anisometropic
      amblyopia. Macular retinal thickness was measured using optical coherence
      tomography at the center and in 1-, 3-, and 6-mm rings. RESULTS: Best-corrected
      visual acuity of the amblyopic eyes was less than that of the internal and
      external controls, and the best-corrected visual acuity of their fellow eyes was
      also less than that of the external controls. Thickness of the central macula and
      a 1-mm ring area in the amblyopic eyes was higher than that of both internal and
      external controls. Difference of central macular thickness >=20 MUm between two
      eyes of the amblyopic children was significantly more than non-amblyopic
      subjects. CONCLUSIONS: Based on the results of this study, the macular retinal
      thickness was significantly higher in moderate to severe amblyopic eyes compared
      to their fellow eyes and external controls. This might be due to macular
      developmental disorders in amblyopic eyes. Therefore, optical coherence
      tomography imaging is recommended if subtle macular abnormalities are suspected
      in moderate to severe amblyopic eyes.

PMID- 30091311
TI  - Characteristics of Patients Who Are Not Responsive to Alternate Patching for
      Overcorrected Intermittent Exotropia.
AB  - PURPOSE: To compare the characteristics of patients with surgically overcorrected
      intermittent exotropia treated with alternate patching. METHODS: The medical
      records of 51 patients who underwent bilateral lateral rectus muscle recession
      for intermittent exotropia and required alternate patching to correct
      postoperative overcorrection were retrospectively reviewed. Patients with
      postoperative esodeviation >=18 prism diopters (PD) were started on alternate
      patching on postoperative day 1, whereas those with postoperative esodeviation of
      10 to 17 PD were started after 2 weeks. Postoperative esodeviation <10 PD was
      considered as slight intentional overcorrection after exotropia surgery. Patients
      not responsive to alternate patching treatment were defined as those with
      postoperative esodeviation >=10 PD after 3 months of treatment. Sex, family
      history, age, refractive error, amblyopia, stereopsis, suppression, type of
      exotropia, surgical method, preoperative and postoperative angle of deviation,
      and start time of alternate patching were compared. RESULTS: Among 51 patients,
      29 patients responded to alternate patching and 22 patients did not respond.
      Female sex (p = 0.04), larger preoperative exodeviation at distance (p = 0.04),
      late onset of postoperative maximal esodeviation (p < 0.01), larger postoperative
      maximal esodeviation at near (p = 0.02), and late initiation of alternate
      patching (p = 0.01) were associated with patients in the non-responsive group.
      Although postoperative angle of deviation was similar for 2 weeks, the angle of
      postoperative esodeviation was significantly larger in the non-responsive group
      than in the responsive group, beginning at 1 month postoperatively. CONCLUSIONS:
      Female sex, large preoperative exodeviation, late initiation of alternate
      patching, and large esodeviation 1-month postoperative predisposed patients to be
      resistant to alternate patching for postoperative overcorrection.

PMID- 30091312
TI  - Effects of Ranibizumab, Bevacizumab, and Aflibercept on Senescent Retinal Pigment
      Epithelial Cells.
AB  - PURPOSE: Anti-vascular endothelial growth factor (VEGF) agents have been used for
      the last 10 years, but their safety profile, including cytotoxicity against
      various ocular cells such as retinal pigment epithelial (RPE) cells, remains a
      serious concern. Safety studies of VEGF agents conducted to date have primarily
      relied on healthy RPE cells. In this study, we assessed the safety of three anti
      VEGF agents, namely, ranibizumab, bevacizumab, and aflibercept, on senescent RPE
      cells. METHODS: Senescent human induced pluripotent stem cell-derived RPE cells
      were generated by continuous replication and confirmed with senescence
      biomarkers. The viability, proliferation, protein expression, and phagocytosis of
      the senescent RPE cells were characterized 3 days after anti-VEGF treatment with
      clinical doses of ranibizumab, bevacizumab, or aflibercept. RESULTS: Clinical
      doses of ranibizumab, bevacizumab, or aflibercept did not decrease the viability
      or alter proliferation of senescent RPE cells. In addition, the anti-VEGF agents
      did not induce additional senescence, impair the protein expression of zonula
      occludens-1 and RPE65, or reduce the phagocytosis capacity of senescent RPE
      cells. CONCLUSIONS: Clinical dosages of ranibizumab, bevacizumab, or aflibercept
      do not induce significant cytotoxicity in senescent RPE cells.

PMID- 30091313
TI  - Generation, Characteristics and Clinical Trials of Ex Vivo Generated Tolerogenic
      Dendritic Cells.
AB  - Dendritic cells (DCs) play a key role not only in the initiation of primary
      immune responses, but also in the development and maintenance of immune
      tolerance. Numerous protocols have been developed to generate tolerogenic DCs
      (tolDCs) ex vivo, and the therapeutic efficacy of ex vivo-generated tolDCs has
      been demonstrated in autoimmune disease animal models. Based on successes in
      small animal models, several clinical trials have been completed or are on-going
      in patients with autoimmune diseases such as rheumatoid arthritis, type 1
      diabetes, multiple sclerosis, and Crohn's disease. Here we describe the methods
      used to generate tolDCs ex vivo, and the common features shared by tolDCs. In
      addition, we overview five completed clinical trials with reported outcomes and
      summarize the tolDC-based clinical trials that are currently registered with the
      U.S. National Institutes of Health. Although the number of tolDC-based clinical
      trials is much smaller than the hundreds of clinical trials using immunogenic
      DCs, tolDC-based treatment of autoimmune diseases is becoming a reality, and
      could serve as an innovative cellular therapy in the future.

PMID- 30091314
TI  - XIST Induced by JPX Suppresses Hepatocellular Carcinoma by Sponging miR-155-5p.
AB  - PURPOSE: The influence of X-inactive specific transcript (XIST) and X-chromosome
      inactivation associated long non-coding RNAs (lncRNAs) just proximal to XIST
      (JPX) on hepatocellular carcinoma (HCC) remains controversial in light of
      previous reports, which the present study aimed to verify. MATERIALS AND METHODS:
      The DIANA lncRNA-microRNA (miRNA) interaction database was used to explore miRNA
      interactions with JPX or XIST. JPX, XIST, and miR-155-5p expression levels in
      paired HCC specimens and adjacent normal tissue were analyzed by RT-qPCR.
      Interaction between XIST and miR-155-5p was verified by dual luciferase reporter
      assay. Expression levels of miR-155-5p and its known target genes, SOX6 and PTEN,
      were verified by RT-qPCR and Western blot in HepG2 cells with or without XIST
      knock-in. The potential suppressive role of XIST and JPX on HCC was verified by
      cell functional assays and tumor formation assay using a xenograft model.
      RESULTS: JPX and XIST expression was significantly decreased in HCC pathologic
      specimens, compared to adjacent tissue, which correlated with HCC progression and
      increased miR-155-5p expression. Dual luciferase reporter assay revealed XIST as
      a direct target of miR-155-5p. XIST knock-in significantly reduced miR-155-5p
      expression level and increased that of SOX6 and PTEN, while significantly
      inhibiting HepG2 cell growth in vitro, which was partially reversed by miR-155-5p
      mimic transfection. JPX knock-in significantly increased XIST expression and
      inhibited HepG2 cell growth in vitro or tumor formation in vivo in a XIST
      dependent manner. CONCLUSION: JPX and XIST play a suppressive role in HCC. JPX
      increases expression levels of XIST in HCC cells, which suppresses HCC
      development by sponging the cancer promoting miR-155-5p.

PMID- 30091315
TI  - Clinical Outcomes of Bilateral Stent-in-Stent Placement Using Self-Expandable
      Metallic Stent for High-Grade Malignant Hilar Biliary Obstruction.
AB  - PURPOSE: Endoscopic bile duct decompression using bilateral self-expandable
      metallic stents (SEMSs) deployed via a stent-in-stent (SIS) method is considered
      a preferred procedure for malignant hilar biliary obstruction (MHBO). However,
      occlusion thereof occurs frequently. Here, we investigated stent patency duration
      and risk factors related to stent obstruction with bilateral SIS placement for
      MHBO at two large centers. MATERIALS AND METHODS: The present study reviewed data
      on patients with MHBO who underwent endoscopic biliary drainage using the SIS
      method. Clinical outcomes, including stent patency duration and patient overall
      survival, were analyzed. Factors associated with stent patency were evaluated
      using Cox proportional hazards models. RESULTS: Seventy patients with MHBO
      underwent endoscopic biliary drainage using the SIS method. Median age was 68
      years old, and median follow-up duration was 140 days (interquartile range, 57
      329). The proportion of high-grade MHBOs (Bismuth type IV) was 57.1%. Median
      stent patency duration with the SIS method was 108 days according to Kaplan-Meier
      curves. Median patient survival analyzed by the Kaplan-Meier method was 181 days.
      Multivariate analysis indicated that higher baseline bilirubin (> 6.1 mg/dL) as
      an independent risk factor related to stent patency (p<0.05). CONCLUSION: In
      endoscopic biliary decompression using SEMS placed with the SIS method,
      obstructive jaundice was a risk factor for stent patency. The SIS method for high
      grade MHBO showed short stent patency.

PMID- 30091316
TI  - High-Carbohydrate Diets and Food Patterns and Their Associations with Metabolic
      Disease in the Korean Population.
AB  - PURPOSE: Although an Asian diet is typically high in carbohydrate and low in fat,
      there has been a steady increase in the rate of cardiometabolic disease in Asian
      countries over the past decade. We evaluated food patterns of a high-carbohydrate
      diet and examined their associations with metabolic disease. MATERIALS AND
      METHODS: Using data from the 2013-2015 Korean National Health and Nutrition
      Examination Survey, we included a total of 13106 subjects aged 20 years or older
      in this study. Diet was divided into seven groups according to the percentage of
      energy from carbohydrates. Food patterns were evaluated as individual servings
      per food group. Multivariate logistic regression was conducted to estimate odds
      ratios (OR) for metabolic disease. RESULTS: The proportions of men and women
      exceeding the recommended range of carbohydrate intake were 58.0% and 60.0%,
      respectively. A higher carbohydrate diet was associated with intake of low energy
      and saturated fats, with more grains and fruit, but less meat, fish, egg, bean
      (MFEB), and dairy consumption. Carbohydrate intake decreased by 3.0-3.4% per
      serving of MFEB and milk. In men, the highest carbohydrate group showed an OR of
      1.35 [95% confidence interval (CI), 0.91 to 1.99] for metabolic syndrome,
      although this failed to show statistical significance. In women, the highest
      carbohydrate group had an OR of 1.38 (95% CI, 1.06 to 1.80) for a reduced level
      of high-density lipoprotein cholesterol. CONCLUSION: This study suggests that a
      very-high-carbohydrate diet for the Korean population is attributable to lower
      consumption of MFEB and dairy products and is associated with several metabolic
      risk factors. The appropriate distribution of macronutrients for the prevention
      and management of metabolic disease should be explored.

PMID- 30091318
TI  - IgE Cross-Reactivity between Humulus japonicus and Humulus lupulus.
AB  - PURPOSE: Japanese hop (Humulus japonicus) is a major cause of weed pollinosis in
      East Asia. However, supplies of commercial allergen extract from this plant have
      not met clinical demand. The pollen of common hop (Humulus lupulus), a closely
      related species, may provide an alternative source if there is strong IgE cross
      reactivity between these two species. We aimed to compare the IgE cross
      reactivity and allergenicity of common hop and Japanese hop pollen. MATERIALS AND
      METHODS: Cross-reactivity was measured by inhibition ELISA. One- and two
      dimensional (2D) gel analyses combined with IgE immunoblotting and mass
      spectrometry [liquid chromatography coupled to electrospray ionization tandem
      mass spectrometry (LC-ESI-MS/MS)] were performed to detect IgE-reactive pollen
      components. RESULTS: Up to 16.7% of IgE reactivity to Japanese hop was inhibited
      by common hop. A 12-kDa protein component of Japanese hop pollen that showed the
      most potent IgE reaction was absent from common hop. Six IgE-reactive components
      from Japanese hop were detected by 2D gel electrophoresis and LC-ESI-MS/MS, but
      showed low Mascot scores, preventing positive identification. CONCLUSION: No
      significant IgE cross-reaction was observed for Japanese and common hop pollen
      allergens. Development of allergy diagnostic and immunotherapeutic reagents based
      on Japanese hop pollen are urgently needed.

PMID- 30091317
TI  - Effects of Early Exercise Rehabilitation on Functional Recovery in Patients with
      Severe Sepsis.
AB  - PURPOSE: Severe sepsis is associated with functional disability among patients
      surviving an acute phase of infection. Efforts to improve functional impairment
      are important. We assessed the effects of early exercise rehabilitation on
      functional outcomes in patients with severe sepsis. MATERIALS AND METHODS: A
      prospective, single-center, case-control study was conducted between January 2013
      and May 2014 at a tertiary care center in Korea. Patients with severe sepsis and
      septic shock were enrolled and randomized to receive standard sepsis treatment or
      intervention. Intervention involved early targeted physical rehabilitation with
      sepsis treatment during hospitalization. Participants were assessed at
      enrollment, hospital discharge, and 6 months after enrollment. Functional
      recovery was measured using the Modified Barthel Index (MBI), Functional
      Independence Measure (FIM), and Instrumental Activities of Daily Living (IADL).
      RESULTS: Forty participants (21 intervention patients) were included in an
      intention-to-treat analysis. There were no significant differences in baseline
      MBI, FIM, and IADL between groups. Intervention yielded greater improvement of
      MBI, FIM, and IADL in the intervention group at hospital discharge, but not
      significantly. Subgroup analysis of patients with APACHE II scores >=10 showed
      significantly greater improvement of physical function at hospital discharge (MBI
      and FIM) in the intervention group, compared to the control group (55.13 vs.
      31.75, p=0.048; 52.40 vs. 31.25, p=0.045). Intervention was significantly
      associated with improvement of MBI in multiple linear regression analysis
      (standardized coefficient 0.358, p=0.048). CONCLUSION: Early physical
      rehabilitation may improve functional recovery at hospital discharge, especially
      in patients with high initial severity scores.

PMID- 30091319
TI  - Self-Reported Physical Activity Is Associated with Lupus Nephritis in Systemic
      Lupus Erythematosus: Data from KORean Lupus Network (KORNET) Registry.
AB  - PURPOSE: The aim of this study was to identify the associations among physical
      activity, disease activity, and organ damage in patients with systemic lupus
      erythematosus (SLE). MATERIALS AND METHODS: A total of 415 patients with SLE were
      consecutively enrolled from the KORean lupus Network (KORNET) registry. This
      registry assessed clinical features, disease activity [Systemic Lupus
      Erythematosus Disease Activity Index 2000 (SLEDAI-2K)], and organ damage
      [Systemic Lupus International Collaborating Clinics/American College of
      Rheumatology (SLICC/ACR) Damage Index (SDI)] upon enrollment in the study. Self
      reported physical activity was measured by the International Physical Activity
      Questionnaire. Statistical analyses were conducted using the Mann-Whitney U test
      and multivariate logistic regression analysis. RESULTS: A significant difference
      in vigorous activity was noted between patients with lupus nephritis (LN) (n=93)
      and those without LN (n=322) (p=0.012), but not in moderate and walking
      activities. In contrast, no differences in physical activity, walking, moderate,
      and vigorous intensity, according to SLEDAI-2K and SDI were found. In addition to
      younger age (p=0.032), high physical component summary of SF-36 (p=0.004) and
      SLEDAI-2K (p=0.038), and less vigorous physical activity were associated with LN
      (p=0.024). However, cardiovascular disease was not associated with physical
      activity in SLE patients. CONCLUSION: This study showed that patients with LN had
      less vigorous physical activity than patients without LN. The results suggest
      that lupus nephritis might be associated with physical activity.

PMID- 30091320
TI  - C-Reactive Protein to Serum Albumin Ratio Is an Independent Predictor of All
      Cause Mortality in Patients with ANCA-Associated Vasculitis.
AB  - PURPOSE: We investigated whether C-reactive protein (CRP) to serum albumin ratio
      (CAR) could be an independent predictor of all-cause mortality in patients with
      antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). MATERIALS
      AND METHODS: We retrospectively reviewed the medical records of 170 patients with
      AAV. We collected clinical and laboratory data. We also examined AAV-related and
      traditional risk factors of all-cause mortality. To assess the hazard ratios of
      variables, we performed univariable and multivariable Cox hazard model analyses.
      RESULTS: The mean age was 55.0 years and 53 patients (31.2%) were male among 170
      patients with AAV (88 microscopic polyangiitis, 43 granulomatosis with
      polyangiitis, and 39 eosinophilic granulomatosis with polyangiitis). ANCA was
      detected in 129 patients (75.9%). The initial mean CRP and serum albumin were
      41.1 (mg/L) and 3.6 (g/dL), and the mean CAR at diagnosis was 14.8. The most
      common risk factor of mortality was hypertension (42.4%), followed by chronic
      kidney disease >=stage 3 (25.9%). Fourteen patients (8.2%) died during the mean
      follow-up of 56.7 months. In both multivariable Cox hazard model analyses, CAR at
      diagnosis was identified as an independent predictor of all-cause of mortality
      comparable to diabetes mellitus (DM). Moreover, patients with CAR >=10.35 and
      having DM exhibited a higher frequency of all-cause mortality than those without.
      CONCLUSION: CAR at diagnosis can be an independent predictor of all-cause
      mortality, comparable to DM, the conventional risk factor of mortality.

PMID- 30091321
TI  - Fish-Mouth Closure of the Pancreatic Stump and Parachuting of the Pancreatic End
      with Double U Trans-Pancreatic Sutures for Pancreatico-Jejunostomy.
AB  - PURPOSE: Leakage of pancreatico-jejunal anastomosis (PJ) remains the primary
      cause of morbidity and mortality after Whipple's operation. To reduce the
      occurrence thereof, the present author recently began to apply a modification of
      the Blumgart method of anastomosis after Whipple's operation (hereinafter
      referred to as Lee's method), with very good results. MATERIALS AND METHODS: The
      modified method and technique utilizes fish-mouth closure of a beveled pancreatic
      stump and parachuting of the pancreatic end with double U trans-pancreatic
      sutures (symmetric horizontal mattress-type sutures between the full thickness of
      the pancreas and the jejunal limb) after duct-to-mucosa pancreatico-jejunostomy.
      RESULTS: Eleven cases of pylorus preserving Whipple's operation have been
      performed without a clinically significant postoperative pancreatic fistula.
      CONCLUSION: This new method (Lee's method) may dramatically reduce the occurrence
      of postoperative pancreatic fistula after Whipple's operation.

PMID- 30091322
TI  - Effects of Oncostatin M on Invasion of Primary Trophoblasts under Normoxia and
      Hypoxia Conditions.
AB  - PURPOSE: To investigate the effect of oncostatin M (OSM) on protein expression
      levels and enzymatic activities of matrix metalloprotainase (MMP)-2 and MMP-9 in
      primary trophoblasts and the invasiveness thereof under normoxia and hypoxia
      conditions. MATERIALS AND METHODS: Protein expression levels and enzymatic
      activities of MMP-2 and MMP-9 in primary trophoblasts under normoxia and hypoxia
      conditions were examined by Western blot and zymography, respectively. Effects of
      exogenous OSM on the in vitro invasion activity of trophoblasts according to
      oxygen concentration were also determined. Signal transducer and activator of
      transcription 3 (STAT3) siRNA was used to determine whether STAT3 activation in
      primary trophoblasts was involved in the effect of OSM. RESULTS: OSM enhanced
      protein expression levels and enzymatic activities of MMP-2 and MMP-9 in term
      trophoblasts under hypoxia condition, compared to normoxia control (p<0.05). OSM
      induced MMP-2 and MMP-9 enzymatic activities were significantly suppressed by
      STAT3 siRNA silencing under normoxia and hypoxia conditions (p<0.05). Hypoxia
      alone or OSM alone did not significantly increase the invasiveness of term
      trophoblasts. However, the invasion activity of term trophoblasts was
      significantly increased by OSM under hypoxia, compared to that without OSM
      treatment under normoxia. CONCLUSION: OSM might be involved in the invasiveness
      of extravillous trophoblasts under hypoxia conditions via increasing MMP-2 and
      MMP-9 enzymatic activities through STAT3 signaling. Increased MMP-9 activity by
      OSM seems to be more important in primary trophoblasts.

PMID- 30091323
TI  - Diagnostic Ability of Swept-Source and Spectral-Domain Optical Coherence
      Tomography for Glaucoma.
AB  - PURPOSE: To compare the diagnostic abilities of swept-source optical coherence
      tomography (OCT) [Deep Range Imaging OCT-1 (DRI-OCT)] and spectral-domain OCT
      (Cirrus HD-OCT) for glaucoma in Korean adults. MATERIALS AND METHODS: This
      retrospective study involved measuring peripapillary retinal nerve fiber layer
      (PP-RNFL) thickness, full macular thickness, and ganglion cell-inner plexiform
      layer (GC-IPL) thickness on two different OCT systems. We used three-dimensional
      optic disc scanning of DRI-OCT and included 12 clock-hour sectors for measurement
      of the PP-RNFL. Areas under receiver operating characteristic curves (AUCs) were
      calculated and compared to determine how well each system could distinguish
      control and glaucomatous patients. RESULTS: Ninety-one healthy and 58
      glaucomatous eyes were included. Both systems could clearly distinguish between
      control eyes and eyes with moderate to severe glaucoma. Among all sectors, the
      AUC values of areas associated with glaucoma were >0.7 for both OCTs. The PP-RNFL
      sector of highest AUC value on both OCTs was the inferior sector of the clock
      hour map (0.968 and 0.959 in DRI-OCT and Cirrus HD-OCT, respectively). Among
      macular thickness sectors, AUC values were highest on both OCTs for the outer
      inferior sector (0.859 and 0.853 in DRI-OCT and Cirrus HD-OCT, respectively). The
      GC-IPL also provided high diagnostic values (DRI-OCT and Cirrus HD-OCT were the
      best in the average and inferior sectors, respectively). CONCLUSION: Although the
      two OCT systems provided different thickness measurements, DRI-OCT exhibited as
      good, if not better, diagnostic ability for glaucoma as Cirrus HD-OCT in Korean
      adults.

PMID- 30091326
TI  - ?

PMID- 30091324
TI  - Aberrant Neural Activation Underlying Idiom Comprehension in Korean Children with
      High Functioning Autism Spectrum Disorder.
AB  - PURPOSE: Autism spectrum disorder (ASD) is a neurodevelopmental disorder
      characterized by social communication impairments and repetitive behaviors or
      restricted interests. Impaired pragmatic language comprehension is a universal
      feature in individuals with ASD. However, the underlying neural basis of
      pragmatic language is poorly understood. In the present study, we examined neural
      activation patterns associated with impaired pragmatic language comprehension in
      ASD, compared to typically developing children (TDC). MATERIALS AND METHODS:
      Functional magnetic resonance imaging (fMRI) was applied to 15 children with ASD
      and 18 TDC using the Korean pragmatic language task. RESULTS: Children with ASD
      were less accurate than TDC at comprehending idioms, particularly when they were
      required to interpret idioms with mismatched images (mismatched condition).
      Children with ASD also showed different patterns of neural activity than TDC in
      all three conditions (neutral, matched, and mismatched). Specifically, children
      with ASD showed decreased activation in the right inferior frontal gyrus (IFG)
      (Brodmann area 47) in the mismatched condition, compared with TDC (IFG;
      t(31)=3.17, p<0.001). CONCLUSION: These results suggest that children with ASD
      face difficulties in comprehending pragmatic expressions and apply different
      pragmatic language processes at the neural level.

PMID- 30091325
TI  - Percutaneous Transhepatic Biliary Drainage in a Two-Month-Old Infant with
      Inspissated Bile Syndrome.
AB  - Inspissated bile syndrome (IBS) is a relatively rare condition. Many treatment
      options are available, including medication, surgery, and surgical interventions,
      such as insertion of cholecystostomy drain, endoscopic retrograde
      cholangiopancreatography, internal biliary drainage, and percutaneous
      transhepatic biliary drainage (PTBD). We herein report the first case of IBS that
      was successfully treated with PTBD in a two-month-old infant in Korea. PTBD was
      initiated on postnatal day 72. On postnatal day 105, we confirmed complete
      improvement and successfully removed the catheters. This report suggests that
      PTBD is a viable and safe treatment option for obstructive jaundice in very young
      infants.

PMID- 30091327
TI  - [Abnormal liver tests during pregnancy - emergency department decision making].
AB  - Abnormal liver biochemical and function tests is common problem among patients in
      emergency department and can result from many different pathologies. In pregnant
      women, causes are sometime life-threating for the mother and the fetus. The role
      of emergency physician is : 1) to differentiate between serious (HELPPS syndrome,
      pre-eclampsia and eclampsia, acute fatty liver of pregnancy) and minor
      (intrahepatic cholestasis, hyperemesis gravidarum) pregnancy related liver
      disease and 2) to recognize non-pregnancy related liver disease.

PMID- 30091328
TI  - [Analgesia and sedation in the pregnant patient].
AB  - Nonobstetric emergencies are frequent during pregnancy. The emergency physician
      must be knowledgeable regarding the physiological changes related to pregnancy,
      and must evaluate the benefit/risk ratio of any medication given to the mother.
      Though maternal side-effects are easy to predict, the fetal risk remains
      difficult to evaluate as medications are numerous and clinical evidence scarce.
      For analgesia as for sedation, the choice will depend on both the clinical
      context of the patient, the desired objective, and the assumed fetal risk.

PMID- 30091329
TI  - [Proctological emergencies in pregnant women].
AB  - Hemorrhoids affect up to 85 % of pregnant women during the last two trimesters.
      The maximum incidence for anal fissure is 20 %. One of the common risk factors is
      constipation promoted during pregnancy. The history of anal pathology, the length
      of delivery and the baby's birth weight also promote these two entities. The
      treatment includes above all hygiene and dietary measures to prevent constipation
      and conservative measures (local anesthetics, sitz baths). Surgical procedures
      should be avoided and indicated only in case of failure of conservative
      treatment. Rectal prolapse is more rare and must be reduced manually before
      surgery. Measures to prevent constipation also apply.

PMID- 30091330
TI  - [Nausea and vomiting in pregnancy].
AB  - Nausea and vomiting in early pregnancy is a common condition at risk to be
      minimized by women or care providers. If not treated in the early stages, it can
      evolve to a severe condition with a morbidity risk for the mother and/or the
      fetus, and expose to public health consequences. Severe forms of nausea and
      vomiting and hyperemesis gravidarum are a clinical diagnosis with nonspecific
      manifestations in addition to biologic and metabolic consequences for mother
      and/or child. Safe and effective treatments can prevent severe consequences if
      used in an early stage of symptoms.

PMID- 30091331
TI  - [Asthmatic exacerbation in pregnant woman].
AB  - The physiological changes in the pregnant woman expose her to a risk of faster
      respiratory decompensation. Asthma affects 2-13% of pregnancies. It is therefore
      important to ensure regular monitoring to allow good control of asthma to reduce
      the risk of exacerbations. Finally, the background treatment, such as
      exacerbations, must be identical to the treatment of other patients.

PMID- 30091332
TI  - [Headaches in pregnancy : management in the emergency department].
AB  - Headaches in a pregnant woman imply a specific management for this population.
      However this article aims to show that the adaptations both from a diagnostic and
      therapeutic standpoint are modest compared to the classical management of the
      headache in the emergency department. Indeed, few etiologies are specific to
      headaches in pregnancy, however they have to be known and excluded. The same
      applies to treatment, which also needs some small but crucial adjustments, given
      the possible consequences on the mother and fetus.

PMID- 30091333
TI  - [Physiological respiratory changes and venous thromboembolic disease during
      pregnancy].
AB  - During physiological pregnancy, changes in lung functions, ventilatory patterns
      and gas exchanges happen. Therefore, the dyspnea experienced by a majority of
      women is usually due to pregnancy itself and is very difficult to differentiate
      from a pathophysiological state. Anamnesis and clinical examination alone do not
      rule out dyspnea of thromboembolic origin. Therefore, a structured approach,
      based on a thromboembolic risk assessment, the application of a specific
      management algorithm and the use of imaging exams is required for emergency
      management of dyspnea occurring during the pregnancy and in the postpartum.

PMID- 30091334
TI  - [Syncope or palpitations during pregnancy].
AB  - Syncope and palpitations are common symptoms during pregnancy ; they are elicited
      by physiological changes. Although they are often benign, careful management is
      essential to eliminate a serious aetiology requiring specialized care. Syncope is
      often of vasovagal origin, but trauma with possible secondary lesions that
      compromise the life-threatening of the mother and foetus must be researched. Some
      palpitations are the manifestation of serious rhythm disorders whose therapeutic
      management depends on their severity and must consider the potential side effects
      on the foetus.

PMID- 30091335
TI  - ?

PMID- 30091336
TI  - ?

PMID- 30091337
TI  - ?

PMID- 30091339
TI  - ?

PMID- 30091338
TI  - ?

PMID- 30091340
TI  - ?

PMID- 30091342
TI  - ?

PMID- 30091341
TI  - ?

PMID- 30091343
TI  - ?

PMID- 30091345
TI  - MRI-Targeted Biopsy for Prostate-Cancer Diagnosis.

PMID- 30091346
TI  - MRI-Targeted Biopsy for Prostate-Cancer Diagnosis.

PMID- 30091347
TI  - Single-Inhaler Triple versus Dual Therapy in Patients with COPD.

PMID- 30091348
TI  - Single-Inhaler Triple versus Dual Therapy in Patients with COPD.

PMID- 30091349
TI  - Single-Inhaler Triple versus Dual Therapy in Patients with COPD.

PMID- 30091350
TI  - Adjuvant Pembrolizumab in Resected Stage III Melanoma.

PMID- 30091351
TI  - Essential Tremor.

PMID- 30091352
TI  - Essential Tremor.

PMID- 30091353
TI  - Essential Tremor.

PMID- 30091354
TI  - [Optimization of Aqueous Two-Phase Extraction of Polysaccharide from Schisandra
      chinensis Using Response Surface Methodology with Box-Behnken Design].
AB  - Objective: To optimize the extraction condition of polysaccharide from Schisandra
      chinensis. Aqueous two-phase extraction( ATPE) method was used, based on Box
      Behnken design with Response surface methodology( BBD-RSM). Methods: solvent
      volume,K2HPO4 and PEG6000 were selected as the investigation factors by the
      single-factor experiment, and the overall desirability( OD)of phase volume ratio,
      partition coefficient and extraction rates were the reponse value. BBD-RSM was
      used to optimize the extraction process. . Results: The optimal parameters were
      as follows,the solvent volume was 5 m L,the addition amount of K2HPO4 was 1. 0 g,
      the addition amount of PEG6000 was 1. 8 g and centrifugation time was 9 min,
      which indicated that the model had a good predictability. The predicted value was
      0. 950,and the deviation between observed and predicted values was 3. 94%
      Conclusion: The ATPE technology is easy to operate and cost-effective for the
      extraction of polysaccharides from Schisandra chinensis.

PMID- 30091355
TI  - [Comparative Study on Efficiency of Extraction of Boiling Powder and Traditional
      Herbal PiecesI. Part of Root and Rhizome,Flower,Leaf and Whole Plant Medicinal
      Materials].
AB  - Objective: To compare the efficiency of extraction of boiling powder and
      traditional herbal pieces of root and rhizome, flower, leaf and whole plant
      medicinal materials for providing a reference for the study and clinical
      application of boiling powder. Methods: 19 kinds of root and rhizome herbs, the 4
      kinds of flower medicinal materials, the 2 kinds of leaf medicinal materials and
      the 2 kinds of whole plant medicinal materials were chosen as the researh object
      and were crushed into boiling powder. The contents of the active ingredients and
      dry extract rate in the water decoction were set as the index to compare the
      extraction efficiency of boiling powder and traditional herbal pieces. Results:
      Boiling powder was added ten times of water, decocted one time, decoction time
      was only ten min, the dry extract rate and the concentration of ingredients in
      the decoction of boiling powder were not less than those in the traditional
      decoction of herbal pieces( ten times of water, decoction time was 50 min),this
      difference was mainly caused by the different of texture density and size of the
      medicinal materials. Conclusion: The boiling powder can not only save time and
      facilitate the patient, but also save a lot of medicinal materials from the
      perspective of chemical medicine, which is beneficial to the sustainable
      development of medicinal material resources.

PMID- 30091356
TI  - [Optimization of Stabilizing Agent of Camptothecin Extraction from Nothapodytes
      pittosporoides Roots].
AB  - Objective: To optimize the stabilizing agent of camptothecin extraction from
      Nothapodytes pittosporoides roots. Methods: The single factor experiment had been
      conducted to study the impact on the yield of camptothecin with different kinds
      of stabilizer, stabilizer concentration and temperature. Results: The results
      showed that with 0. 5% ferrous sulfate at 80 C,the best concentration of
      camptothecin extraction from Nothapodytes pittosporoides roots was got, and the
      yield of camptothecin after concentration reached to 94. 58%. Conclusion: This
      process method is efficient and simple, which can be used to solve camptothecin
      reduction when the extract is concentrated, and the method is benefit for the
      industrialization of camptothecin extraction.

PMID- 30091357
TI  - [Effects of Biyuanshu on Molecular Chaperone HSP70 and Cofactor CHIP Expression
      of Nasal Sinuses Mucosa Epithelial in Mice Chronic Rhinosinusitis Model].
AB  - Objective: To investigate effects of Biyuanshu( BYS) on molecular chaperone HSP70
      and carboxyl terminus of HSC70 /HSP70-interacting protein( CHIP) expression of
      nasal sinuses mucosa epithele in mice Chronic rhinosinusitis( CRS) model, and to
      explore the BYS intervention mechanism from the point of molecular chaperone
      system. Methods: 140 C57 male mice were randomly divided into normal group, sham
      operation group, model group, western medicine group, BYS low-dosage group, BYS
      medium-dosage group, BYS high-dosage group, with 20 mice in each group, and CRS
      model was established. With corresponding drug treatment for 14 days. Nasal
      sinuses mucosa tissue was collected to observe pathological alterations after HE
      dyeing, and HSP70 and its cofactor CHIP mRNA expression in nasal sinuses mucosa
      epithele were detected by real-time PCR, and the protein expression and IKK
      activity were detected by Western blotting. Results: Model group appeared large
      necrotic and falling-off areas, apparently accompanied with chronic inflammatory
      cell infiltration. Nasal sinuses mucosa epithelial chaperon HSP70 and its
      cofactor CHIP expressions were much lower in CRS group than normal group and slam
      operation group( P < 0. 05 or P < 0. 01),p-IKKalpha / beta expression in model
      group was obviously higher than normal group and slam operation group( P < 0.
      01). Compared to model group, BYS medium-dosage and high-dosage groups presented
      well-repaired epithele in alignment, with fewer chronic inflammatory cell
      infiltration. Furthermore, expression of chaperon HSP70 and its cofactor CHIP in
      nasal sinuses mucosa epithelium were much higher than model group( P < 0. 01),but
      the p-IKKalpha / beta expression was lower( P < 0. 01). Conclusion: BYS can
      upregulate chaperon HSP70 and its cofactor CHIP to enhance intracellular
      protection from inflammatory protein injury mice, and reduce IKK activity to
      intervene on downstream NF-kappaB signaling pathway. BYS can be in favor of nasal
      sinuses mucosa epithelial repairmen.

PMID- 30091358
TI  - [Effects and Mechanism of Yisui Lixue Decoction on Dyshaematopoiesis of Marrow
      Cell in Model Rats with Myelodysplastic Syndrome Induced by Dimethyl
      Benzanthracene].
AB  - Objective: To investigate the effects and mechanism of Yisui Lixue decoction on
      dyshaematopoiesis of marrow cell in model rat with myelodysplastic syndrome( MDS)
      induced by dimethyl benzanthracene( DMBA). Methods: The model rats with MDS were
      induced by the chemical mutagens DMBA,which randomly divided into normal control
      group,physiological saline model group,compound Zaofan pill group, low dose group
      and high dose group of Yisui Lixue decoction,with 12 rats in each group. The rats
      were treated with different drugs for one month from the 14 th day, and executed
      on the 31 th day. The degree of bone marrow hyperplasia,dyshaematopoiesis,IL-3
      and TNF-alpha in serum, the expression of CD34,and the proportion of the original
      cells were measured in the experimental group. Results: Compared with the normal
      control group, the degree of bone marrow hyperplasia was hyperactive and
      dyshaematopoiesis was more obvious in the physiological saline model group; and
      in the treatment group were improved, especially in the high dose group of Yisui
      Lixue decoction. Compared with the normal control group, the content of IL-3 in
      serum was decreased and TNF-alpha was increased( P< 0. 01) in the physiological
      saline model group; the content of IL-3 was increased( P < 0. 05) and THF-alpha
      was decreased( P < 0. 05) in the treatment groups, the effects were more obvious(
      P < 0. 01) in the high dose group of Yisui Lixue decoction. Compared with the
      normal control group, the positive expression of CD34 and CD45 were significantly
      increased( P < 0. 01) in the physiological saline model group, and those in
      treatment groups were decreased( P < 0. 05),especially in the high dose group of
      Yisui Lixue decoction( P < 0. 01). Conclusion: Yisui Lixue decoction can improve
      the degree of bone marrow hyperplasia, dyshaematopoiesis, elevate the expression
      of IL-3,reduce the expression of TNF-alpha and CD34 and CD45.

PMID- 30091359
TI  - [Study of Yiqi Chutan Formula in Suppressing A549 Lung Cancer by Regulating
      Unfolded Protein Response].
AB  - Objective: To study the inhibition and mechanism on lung cancer A549 cells
      xenografts in BALB / c nude mice. Methods: 40 BALB / c mice were selected to
      establish lung cancer xenografts models with human lung adenocarcinoma A549
      cells,which were randomized into model group,cisplatin group( 0. 002 g / kg),
      Yiqi Chutan Formula low-dose group( 3. 0 g / kg),Yiqi Chutan Formula high-dose
      group( 6. 0 g / kg) and combination group[Yiqi Chutan Formula 6. 0( g / kg) /
      cisplatin 0. 002( g / kg) ], with eight mice in each group. Yiqi Chutan Formula
      was given once a day with 0. 2 m L from 8th day after modeling,and successive
      medication for14 days. After given cisplatin with 0. 2 m L by intraperitoneal
      injection once a day in 17 th day,and modeling for 5 days. The tumor weight and
      tumor volume were detected. And the tumor inhibitory rate were calculated. The
      expression of CNX and XBP1 was detected by immunohistochemistry,Western blotting
      and and real-time quantitative PCR. Results: Compared with the model group, the
      tumor weight and the tumor volume were lower in cisplatin group, Yiqi Chutan
      Formula high-dose group and combination group( P < 0. 01);and the combination
      group was better than the cisplatin group( P < 0. 01). The results of
      immunohistochemistry, Western blotting and real-time quantitative PCR showed
      that, compared with the model group, the expression of CNX and XBP1 were lower in
      cisplatin group, Yiqi Chutan Formula high-dose group and combination group( P <
      0. 01),and the combination group was better than the cisplatin group( P < 0. 05
      or P < 0. 01). Conclusion: Yiqi Chutan Formula can inhibit A549 lung cancer cells
      in BALB/c nude mice. Combined with chemotherapy drugs, the killing effect on lung
      cancer can be enhanceed. Its mechanism may be related to down-regulating CNX and
      XBP1 to inhibit the unfolded protein response to lead to apoptosis.

PMID- 30091360
TI  - Simple and Economical Analytical Voltammetry in 15 MUL Volumes: Paracetamol
      Voltammetry in Blood Serum as a Working Example.
AB  - Reported is a three-electrode mini-cell for voltammetry in 15 MUL solutions. The
      key device component is a rolled platinum foil of an inverted omega-shaped cross
      section, which functions as both the electrolyte container and the counter
      electrode. The analytical assembly was completed with properly sized working and
      reference electrodes in the two terminals of the quasi-tubular Pt trough. Its
      applicability in electrochemical assays of 15 MUL solutions was verified by redox
      mediator voltammetry at graphite and noble metal sensors and by trace lead
      stripping voltammetry. Real sample analysis was adequate for drug detection in a
      volunteer's blood, drawn before and 1 or 4 h after ingestion of paracetamol. In
      line with its known pharmacokinetics, lack of drug as well as drug presence and
      clearance were proven correctly in the three samples. The mini-cell here is easy
      to assemble and operate, indefinitely reusable, and offers valuable economy in
      chemical usage and minimal waste. This is primarily a versatile device for
      electrochemical laboratory analysis of samples that are available only in small
      quantities, and cost-effective quantitative screens for expensive high-molecular
      weight compounds, products of microsynthesis, physiological microdialysis
      collections, and finger-prick blood sampling are seen as feasible targets.

PMID- 30091361
TI  - Three Switchable Orthogonal Dynamic Covalent Reactions and Complex Networks Based
      on the Control of Dual Reactivity.
AB  - Achieving complexity is central to the creation of chemical systems, inspired by
      natural systems. Herein we introduce a strategy of switchable orthogonal dynamic
      covalent chemistry (DCC) toward the regulation of complex dynamic networks. The
      control of dual reactivity of tautomers and resulting pathways allowed reversible
      covalent bonding of a large scope of primary amines, secondary amines, alcohols,
      and thiols with high efficiency. The selection of reaction pathways next enabled
      the realization of orthogonal but switchable dynamic covalent reactions (DCRs)
      with nucleophile pairs of amine/alcohol, alcohol/thiol, and amine/thiol by
      varying protonation and oxidation states. Control experiments confirmed the
      crucial role of dual reactivity on the stability and switchability of DCRs. The
      specificity toward amines, alcohols, and thiols, as well as interconversion
      between their corresponding assemblies, was further accomplished in one vessel,
      thus creating tunable communicating networks with three types of DCRs. Moreover,
      the switchable orthogonality combined with differential reactivity of multiple
      sulfonamides and nucleophiles enhanced the complexity within dynamic libraries.
      The generality and versatility of our approaches should facilitate their
      incorporation into many aspects of chemistry endeavors.

PMID- 30091362
TI  - Injectable Nanoreinforced Shape-Memory Hydrogel System for Regenerating Spinal
      Cord Tissue from Traumatic Injury.
AB  - Traumatic injury in the central nervous system can lead to loss of functional
      neurons. Transplantation of neural progenitors is a promising therapeutic
      strategy. However, infusion of dissociated cells often suffers from low
      viability, uneven cell distribution, and poor in vivo engraftment that could be
      reinforced by a better cell delivery system. Here, we develop an injectable
      composite hydrogel system for use as a minimally invasive treatment of spinal
      cord injury (SCI) using motor neurons (MNs) derived from embryonic stem cells
      (ESCs). The composite hydrogel is based on a modified gelatin matrix integrated
      with shape-memory polymer fibers. The gelatin matrix creates a local
      microenvironment for cell assembly and also acts as a lubricant during injection
      through a fine catheter. Notably, shape-memory fiber scaffolds are able to
      recover to maintain the microstructures even after dramatic deformation from
      injection operation, providing the necessary support and guidance for motor
      neuron differentiation. We find that the composite hydrogel with an aligned fiber
      scaffold greatly improves the viability of ESCs and their differentiation toward
      MNs both in vitro and in vivo. When transplanted to SCI animals by injection, the
      ESC-loaded composite hydrogels are identified to significantly enhance tissue
      regeneration and motor function recovery in mice. With this proof-of-concept
      study, we believe that the injectable composite hydrogel system provides a
      promising solution for in vivo cell delivery with minimum invasiveness and can be
      readily extended to other stem-cell-based regenerative treatments.

PMID- 30091363
TI  - Biomimetic Silicification on Membrane Surface for Highly Efficient Treatments of
      Both Oil-in-Water Emulsion and Protein Wastewater.
AB  - The worldwide water crisis and water pollution have put forward great challenges
      to the current membrane technology. Although poly(vinylidene fluoride) (PVDF)
      porous membranes can find diverse applications for water treatments, the inherent
      hydrophilicity must be tuned for an energy-/time-saving process. Herein, the
      surface wettability of PVDF membranes transforming from highly hydrophobicity to
      highly hydrophilicity was realized via one-step reaction of plant-derived phenol
      gallic acid and gamma-aminopropyltriethoxysilane in aqueous solutions. The
      surface hydrophilicization can be achieved on porous PVDF membranes by virtue of
      integration of a mussel-inspired coating and in situ silicification via a
      "pyrogallol-amino covalent bridge" toward excellent antifouling performance and
      highly efficient infiltration ability for oily emulsion and protein wastewater
      treatment. The water flux of a surface-manipulated microfiltration membrane can
      reach ca. 9246 L m-2 h-1 (54-fold increment compared to that of pristine
      membrane), oil rejection >99.5% in a three-cycle emulsion separation; the
      modified ultrafiltration membrane demonstrated benign performance in bovine serum
      albumin protein interception (rejection as high as ca. 96.6% with water flux of
      ca. 278.2 L m-2 h-1) and antifouling potential (increase of ca. 70.8%). Our in
      situ biomimetic silicification under "green" conditions exhibits the great
      potential of the developed strategy in fabrication of similar multifunctional
      membranes toward environmental remediation.

PMID- 30091364
TI  - Direct Multielemental Trace Determinations in Plutonium Samples by Total
      Reflection X-ray Fluorescence Spectrometry Using a Very Small Sample Amount.
AB  - A simple, safe, and sensitive method for direct multielemental trace
      determinations in plutonium samples using total reflection X-ray fluorescence
      (TXRF) spectrometry has been developed. A very small volume (2 MUL) of the sample
      solutions was deposited on TXRF supports after separation of the plutonium matrix
      from these solutions. Since the amount of the plutonium deposited on the supports
      was in the ng level only fixed on the supports and the specimen spots were not
      disturbed during the sample preparation, the samples could be analyzed directly
      without putting the instrument in a glovebox. This approach avoided a cumbersome
      operation of the instrument in a glovebox, which is normally utilized for Pu
      based samples using other techniques. Similarly, the requirement of small amounts
      of the samples minimized the radiation dose to the operator as well as a
      cumbersome problem of management of radioactive analytical waste of plutonium
      samples. The samples were analyzed using the TXRF spectra of the specimens,
      concentration of the internal standard Se or Ga and predetermined sensitivity
      values. The elemental detection limits for the elements K-Sr varied from 1.06 to
      0.09 ng. The elements K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, Sr, Ba, Tl, and Pb were
      analyzed at MUg/mL level. The analytical results of TXRF determinations showed
      average relative standard deviation (RSD) value of 4.5% (1sigma, n = 3) and the
      TXRF determined results deviated from the expected values by 5.9% on average for
      samples prepared by adding multielements in plutonium solutions. Two real
      plutonium samples were also analyzed in similar manner. For the real plutonium
      sample solution the average RSD values of TXRF determinations were 10.6% (1sigma,
      n = 3) for the elemental concentrations in the range of 0.2 to 61 MUg/mL. These
      values are comparable with conventional trace element analytical techniques with
      added advantages mentioned above.

PMID- 30091365
TI  - Cells Adhering to 3D Vertical Nanostructures: Cell Membrane Reshaping without
      Stable Internalization.
AB  - The dynamic interface between the cellular membrane and 3D nanostructures
      determines biological processes and guides the design of novel biomedical
      devices. Despite the fact that recent advancements in the fabrication of
      artificial biointerfaces have yielded an enhanced understanding of this
      interface, there remain open questions on how the cellular membrane reacts and
      behaves in the presence of sharp objects on the nanoscale. Here we provide a
      multifaceted characterization of the cellular membrane's mechanical stability
      when closely interacting with high-aspect-ratio 3D vertical nanostructures,
      providing strong evidence that vertical nanostructures spontaneously penetrate
      the cellular membrane to form a steady intracellular coupling only in rare cases
      and under specific conditions. The cell membrane is able to conform tightly over
      the majority of structures with various shapes while maintaining its integrity.

PMID- 30091366
TI  - Cannulated Intramedullary Screw Fixation of Distal Fibular Fractures.
AB  - BACKGROUND: Open reduction and internal fixation (ORIF) methods, primarily plates
      and screws, remain the standard of treatment for distal fibular fractures. This
      study evaluates the use of a cannulated intramedullary screw as a minimally
      invasive treatment method for distal fibular fractures, which has not been
      reported in the current literature. METHODS: This retrospective study included 45
      patients with distal fibular fractures treated with cannulated intramedullary
      screw fixation. All patients included in the cohort had a soft-tissue condition
      and/or comorbidity. The mean age was 54 years. The Weber classification system
      was used to assess the type of fracture. Average time to union, average time to
      weight bearing, and complications were monitored. RESULTS: Reduction quality
      criteria were collected using previously published guidelines. Accordingly,
      reduction was determined to be good in 25 cases, fair in 15, and poor in 5. A low
      complication rate of 4% was reported. Average time to union was 10 weeks (range =
      8-36 weeks), whereas average time to weight bearing was 14 weeks (range = 8-40
      weeks). CONCLUSION: Cannulated intramedullary screw fixation can serve as a
      minimally invasive, safe, and satisfactory treatment for distal fibular fractures
      with resulting high union rates and low complication rates. LEVELS OF EVIDENCE:
      Level IV: Retrospective, case series.

PMID- 30091367
TI  - Community treatment orders are (somewhat) effective: Their future in the context
      of rights-based mental health law.

PMID- 30091368
TI  - Application of prophylactic cranial irradiation in limited-stage small-cell lung
      cancer: which patients could benefit?
AB  - AIM: To analyze the role of prophylactic cranial irradiation (PCI) on the
      survival for patients with limited-stage small-cell lung cancer (LS-SCLC).
      PATIENTS & METHODS: We screened patients from Surveillance, Epidemiology and End
      Results database. Kaplan-Meier analysis and Cox proportional hazard model were
      used to evaluate factors influencing survival. RESULTS: LS-SCLC patients who
      receiving PCI were associated with better overall survival (OS) (p < 0.001) and
      cancer-specific survival (CSS) (p < 0.001). Multivariable Cox analysis revealed
      PCI was an independent prognostic factor for OS (p < 0.001) and CSS (p < 0.001).
      In subgroup analysis, there were no OS and CSS differences between PCI and no PCI
      groups in black patients and patient with a tumor size <5 cm (all p > 0.05).
      CONCLUSION: PCI remains an effective method for most LS-SCLC patients. However,
      caution should be taken in recommending PCI for black patients and patients with
      a tumor size <5 cm. Further clinical trials are necessary to validate our results
      and identify the most suitable patients for PCI in the modern era.

PMID- 30091369
TI  - Reporting and Description for Congenital Middle Ear Malformations to Facilitate
      Surgical Management.
AB  - INTRODUCTION: The aim of this work was to report and describe the different types
      of congenital middle ear malformations in order to guide surgical treatment
      approaches and improve outcomes for affected patients. METHODS: The authors
      reviewed patients with congenital middle ear malformations who received surgical
      treatment between September 2010 and March 2017. Patient characteristics, middle
      ear deformities, and surgical procedures were documented. RESULTS: In this
      retrospective study, 35 patients were reviewed. A description of middle ear
      malformation was proposed that considers ear embryogenesis and focuses on stapes
      deformity, with the main purpose of facilitating surgical approach selection to
      reconstruct the ossicular chain. Patients were classified into 3 categories: type
      I (19 cases), mobile stapes footplate, which included type Ia with normal stapes
      suprastructure and type Ib with abnormal stapes suprastructure; type II (4
      cases), fixed stapes footplate, which included type IIa with normal ossicular
      chain and type IIb with abnormal ossicular chain; and type III (12 cases), oval
      window bony atresia or aplasia, with or without round window atresia. Types II
      and III could have concomitant aberrant facial nerve. Different surgical
      approaches are described. CONCLUSIONS: The authors describe the different types
      of congenital middle ear malformations. This category description considers ear
      embryogenesis and is focused on stapes deformity. It may provide better
      understanding of disease development and guide modern hearing reconstructive
      surgery.

PMID- 30091370
TI  - Papillary-Type Carcinoma of the Thyroglossal Duct Cyst: The Case for Conservative
      Management.
AB  - OBJECTIVES: Thyroglossal duct cyst (TGDC) is the most common congenital neck
      mass, presenting in up to 7% of the population. TGDC carcinoma is much less
      common, occurring in roughly 1% of patients diagnosed with TGDC. The vast
      majority of these tumors are papillary-type thyroid cancer. Given its rarity,
      there is wide variation in management recommendations for this disease. Extent of
      surgical management and need for adjuvant therapy including radioactive iodine
      ablation (RAI) are particularly debated, with some authors arguing aggressive
      therapy including RAI for any patients who undergo concurrent thyroidectomy with
      the Sistrunk procedure for TGDC carcinoma. We present a series of patients
      treated for TGDC carcinoma at our institutions and discuss our management
      algorithm. METHODS: This is a retrospective chart review of patients with TGDC
      treated at 2 separate institutions. Factors reviewed included patient age, sex,
      preoperative diagnosis, preoperative work-up, extent of therapy, and use of
      adjuvant therapy. RESULTS: Six patients who were treated for TGDC carcinoma at
      our institutions were identified. One patient was excluded because the patient
      had been treated at an outside facility prior to referral. All patients had
      papillary-type thyroid cancer. One patient underwent the Sistrunk procedure
      alone, and the remaining 4 underwent the Sistrunk procedure plus total
      thyroidectomy. Two of 4 patients were noted to have malignancy in the thyroid.
      Two of 4 patients who underwent thyroidectomy additionally received adjuvant RAI.
      CONCLUSION: Thyroglossal duct cyst carcinoma is uncommon and management is
      controversial. In low-risk patients (single tumor focus, negative margins, normal
      preoperative neck/thyroid imaging, no extension of TGDC carcinoma beyond the cyst
      wall), the Sistrunk procedure alone with observation of the thyroid may be
      sufficient. In this patient population, RAI is unlikely to be of any substantial
      benefit.

PMID- 30091371
TI  - Clinical outcomes with long-term sorafenib treatment of patients with
      hepatocellular carcinoma: a multicenter real-life study.
AB  - AIM: This multicenter field-practice study evaluates outcomes of long-term
      sorafenib in hepatocellular carcinoma (HCC) patients. METHODS: Consecutive HCC
      patients on sorafenib were enrolled. We evaluated those receiving sorafenib for
      >=12 months. RESULTS: Out of 800 patients on sorafenib, 81 (10%) received long
      term treatment. Median duration of treatment was 22.7 months (range: 12.3-92.6).
      Only 21 (26%) reported grade 3/4 adverse events. Complete response was reported
      in 11 patients (14%). Median overall survival was 34.8 months (95% CI: 29.9
      44.3). Only baseline Child-Pugh class was associated with survival. CONCLUSION:
      Sorafenib could result in long-term control of HCC in a relevant proportion of
      patients. Given the availability of regorafenib in the second-line setting, an
      earlier introduction of systemic therapy may be considered according to clinical
      indications.

PMID- 30091372
TI  - Psychotherapeutic interventions for chronic pain: Evidence, rationale, and
      advantages.
AB  - Background Long-term use of opioids to treat chronic pain incurs serious risks
      for the individual-including misuse, abuse, addiction, overdose and death-as well
      as creating economic, social, and cultural impacts on society as a whole. Chronic
      pain and substance use disorders are often co-morbid with other medical problems
      and at the present time, primary care clinicians serve most of this population.
      Primary care clinicians would benefit from having alternatives to opioids to
      employ in treating such patients. Method We electronically searched different
      medical databases for studies evaluating the effect of nonpharmacological
      treatments for chronic pain. We describe alternative approaches for the treatment
      of chronic pain and cite studies that provide substantial evidence in favor of
      the use of these treatments. Results Cognitive behavioral therapy, acceptance and
      commitment therapy, and mindfulness-based programs have well-documented
      effectiveness for the treatment of chronic nonmalignant pain. Integration of such
      behavioral health therapies into primary care settings may optimize health
      resources and improve treatment outcomes. Conclusion Evidence-based psychotherapy
      for chronic pain has established efficacy and safety and improves quality of life
      and physical and emotional functioning. Such interventions may be used as an
      alternative or adjunct to pharmacological management. Chronic opioid use should
      be reserved for individuals undergoing active cancer treatment, palliative care,
      or end-of-life care.

PMID- 30091373
TI  - Doctors at times of national instability: What Balint seminars reveal.
AB  - Background It is not known in what ways is the doctor whose practice is secure in
      a clinic challenged to maintain a therapeutic doctor-patient relationship when
      confronting a flood of immigrants within a country that is politically volatile,
      internally fractionalized, and surrounded by sporadic military incursions?
      Methods During Balint seminars, a family medicine resident presents a troubling
      case which all group members reflect upon from the perspective of the doctor, the
      patient, and their relationship. Balint leaders later debrief and review the work
      of the group. Lebanon has passed through many political, social, and religious
      conflicts and was affected by the onset of the Syrian Civil War in 2010. The
      Balint leaders had begun to see in resident case presentations reflections of
      war's disruption of the doctor-patient relationship. Two Balint leaders reviewed
      a log of all the cases between 2013 and 2016. Results In our observations, the
      discussion of the presented cases mirrored the cultural, social, religious, and
      political context of the country. First, the political situation was reflected in
      the dynamics of the group: agitation, conflicts, hopelessness, and a search for
      norms. Second, the residents subconsciously chose words in their discussion that
      reflect the country's situation. Third, the presented case was stirred by a
      tragic war-related event. Conclusions The social/political/religious context in
      which the physician is practicing distracts the doctor from fulfilling his/her
      professional role. Balint seminars are an example of direct, experiential
      learning that provide an excellent opportunity for the special training of
      primary care physicians who deal with refugees and citizens to self-reflect on
      war's impact on them and their profession.

PMID- 30091374
TI  - Effects of endometrial preparations and transferred embryo types on pregnancy
      outcome from patients with advanced maternal age.
AB  - : We explored the strategy of frozen-thawed embryo transfer (FET) in the women
      with advanced maternal age (AMA). We first determined the age cut-off point of
      AMA by retrospective analysis of pregnancy outcomes in the patients undergoing
      FET. The patients with AMA were divided into 3 groups including natural cycle
      (NC) group, controlled ovarian stimulation (COS) group, and hormone replacement
      therapy (HRT) group, and simultaneously were divided into 2 groups including
      cleavage-stage embryo transfer (CET) group and blastocyst-stage embryo transfer
      (BET) group. The clinical pregnancy, embryo implantation, abortion and live birth
      rates were compared between the 3 groups and the 2 groups, respectively. We found
      that in the women aged 38 years or over, the clinical pregnancy rate and live
      birth rate were all significantly decreased as compared with the younger than 38
      year-old women (all P < 0.05), so the women aged 38 years or over were regarded
      as the patients with AMA in this study. In the patients with AMA, the clinical
      pregnancy rate and live birth rate were 22.95% and 18.03% in NC group, 23.68% and
      15.79% % in COS group as well as 24.58% and 15.92% in HRT group, and there were
      no significant differences in the clinical pregnancy rate and live birth rate
      between the 3 groups. However, the clinical pregnancy rate (42.96% vs 15.87%) and
      embryo implantation rate (32.26% vs 9.67%) were all significantly higher in the
      BET group than in the CET group (all P < 0.01). We conclude that in the women
      aged 38 years or over, the choice of endometrial preparation protocols may depend
      on the individual specific conditions because the endometrial preparation
      protocols do not affect FET outcome, but BET can obtain better FET outcomes as
      compared with CET. ABBREVIATIONS: AMA: advanced maternal age; FET: frozen-thawed
      embryo transfer; NC: natural cycle; COS: controlled ovarian stimulation; HRT:
      hormone replacement therapy; CET: cleavage-stage embryo transfer; BET: blastocyst
      stage embryo transfer; LH: luteinizing hormone; HCG: human chorionic
      gonadotropin; HMG: human menopausal gonadotropin; FSH: follicle-stimulating
      hormone; BMI: body mass index.

PMID- 30091375
TI  - Specialized psychotherapies for adults with borderline personality disorder: A
      systematic review and meta-analysis.
AB  - OBJECTIVE: Borderline personality disorder affects up to 2% of the population and
      is associated with poor functioning, low quality of life and increased mortality.
      Psychotherapy is the treatment of choice, but it is unclear whether specialized
      psychotherapies (dialectical behavior therapy, mentalization-based treatment,
      transference-focused therapy and schema therapy) are more effective than non
      specialized approaches (e.g. protocolized psychological treatment, general
      psychiatric management). The aim of this systematic review is to investigate the
      effectiveness of these psychotherapies. METHODS: PubMed, PsycINFO, CINAHL, EMBASE
      and CENTRAL were searched from inception to November 2017. Included randomized
      controlled trials were assessed on risk of bias and outcomes were meta-analyzed.
      Confidence in the results was assessed using the Grading of Recommendations
      Assessment, Development and Evaluation method. The review has been reported
      following Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. RESULTS: A total of 20 studies with 1375 participants were included.
      Specialized psychotherapies, when compared to treatment as usual or community
      treatment by experts, were associated with a medium effect based on moderate
      quality evidence on overall borderline personality disorder severity
      (standardized mean difference = -0.59 [95% confidence interval: -0.90, -0.28]),
      and dialectical behavior therapy, when compared to treatment as usual, with a
      small to medium effect on self-injury (standardized mean difference = -0.40 [95%
      confidence interval: -0.66, -0.13]). Other effect estimates were often
      inconclusive, mostly due to imprecision. CONCLUSION: There is moderate quality
      evidence that specialized psychotherapies are effective in reducing overall
      borderline personality disorder severity. However, further research should
      identify which patient groups profit most of the specialized therapies.

PMID- 30091376
TI  - So we beat on, boats against the current, borne back ceaselessly into the past -
      Continued inaction on public mental health services.

PMID- 30091377
TI  - Maintenance of Contractile function of isolated airway smooth muscle after
      cryopreservation.
AB  - RATIONALE: Isolated human airway smooth muscle (ASM) tissue contractility studies
      are essential for understanding the role of ASM in respiratory disease, but
      limited availability and cost render storage options necessary for optimal use.
      However, to date no comprehensive study of cryopreservation protocols for
      isolated ASM has been performed. METHODS: We tested several cryostorage protocols
      on equine trachealis ASM, using different cryostorage media (1.8M dimethyl
      sulfoxide and fetal bovine serum [FBS] or Krebs-Henseleit [KH]) and different
      degrees of dissection (with or without epithelium and connective tissues
      attached) prior to storage. We measured methacholine (MCh), histamine and
      isoproterenol (Iso) dose responses and electrical field stimulation (EFS) and MCh
      force velocity curves. We confirmed our findings in human trachealis ASM stored
      undissected in FBS. RESULTS: Maximal stress response to MCh was decreased more in
      dissected than undissected equine tissues. EFS force was decreased in all equine
      but not in human cryostored tissues. Furthermore, in human cryostored tissues,
      EFS unloaded shortening velocity was decreased and Iso response was potentiated
      after cryostorage. Overnight incubation with 0.5 or 10% FBS did not recover
      contractility in the equine tissues but potentiated Iso response. Overnight
      incubation with 10% FBS in human tissues showed maximal stress recovery and
      maintenance of other contractile parameters. CONCLUSION: ASM tissues can be
      cryostored while maintaining most contractile function. We propose an optimal
      protocol for cryostorage of ASM as undissected tissues in FBS or KH solution
      followed by dissection of the ASM bundles and a 24h incubation with 10% FBS
      before mechanics measurements.

PMID- 30091378
TI  - The Neutrophil Chemoattractant Peptide Proline-Glycine-Proline Is Associated With
      Acute Respiratory Distress Syndrome (ARDS).
AB  - ARDS is characterized by unrelenting PMN inflammation and vascular permeability.
      The matrikine proline-glycine-proline (PGP) and acetylated PGP (Ac-PGP) have been
      shown to induce PMN inflammation and endothelial permeability in vitro and in
      vivo. In this study, we investigated the presence and role of airway PGP peptides
      in acute lung injury (ALI)/ARDS. P. aeruginosa-derived LPS was instilled
      intratracheally (i.t) in mice to induce ALI and increased Ac-PGP with neutrophil
      inflammation was noted. The PGP inhibitory peptide, RTR (arginine-threonine
      arginine), was administered (i.t.) 30 minutes before or 6 hours after LPS
      injection. Lung injury was evaluated by detecting neutrophil infiltration and
      permeability changes in the lung. Pre- and post-treatment with RTR significantly
      inhibited LPS-induced ALI by attenuating lung neutrophil infiltration, pulmonary
      permeability and parenchymal inflammation. To evaluate the role of PGP levels in
      ARDS, mini-bronchoalveolar lavage was collected from 9 ARDS, 4 cardiogenic edema
      and 5 non- lung disease ventilated patients. PGP and myeloperoxidase (MPO) levels
      were measured and correlated with APACHE score, Pao2 to Fio2 (PF) and ventilator
      days. PGP and MPO levels in subjects with ARDS were significantly higher than
      cardiogenic edema and non- lung disease ventilated patients. Preliminary
      examination in both ARDS and non-ARDS populations demonstrated PGP levels
      significantly correlated with PF ratio, APACHE score and duration on ventilator.
      These results demonstrate an increase burden of PGP peptides in ARDS and suggest
      the need for future studies in ARDS cohorts to examine correlation with key
      clinical parameters.

PMID- 30091379
TI  - Comparison of the effects of e-cigarette vapor with cigarette smoke on lung
      function and inflammation in mice.
AB  - Electronic cigarettes (e-cig) are advertised as a less harmful nicotine delivery
      system or as a new smoking cessation tool. We aimed to assess the in vivo effects
      of e-cigarette vapor in the lung and to compare them to those of cigarette smoke
      (CS). We exposed C57BL/6 mice for either 3 days or 4 weeks to ambient air, CS or
      e-cig vapor containing: i) propylene glycol/vegetable glycerol (1:1; PG:VG-Sol),
      ii) PG:VG with nicotine (G:VG-N), or iii) PG:VG with nicotine and flavor (PG:VG-
      N+F) and determined oxidative stress, inflammation and pulmonary mechanics. E-cig
      vapors, especially PG:VG- N+F, increased bronchoalveolar lavage fluid (BALF)
      cellularity, Muc5ac production, as well as BALF and lung oxidative stress markers
      at least comparably and in many cases more than CS. BALF protein content at both
      time points studied was only elevated in the PG:VG- N+F group. After 3 days,
      PG:VG-Sol altered tissue elasticity, static compliance and airway resistance,
      while after 4 weeks, CS was the only treatment adversely affecting these
      parameters. Airway hyperresponsiveness in response to methacholine was increased
      similarly in the CS and PGVG-N+F groups. Our findings suggest that exposure to e
      cig vapor can trigger inflammatory responses and adversely affect respiratory
      system mechanics. In many cases, the added flavor in e-cigs exacerbated the
      detrimental effects of e-cig vapor. We conclude that both e-cig vaping and
      conventional cigarette smoking negatively impact lung biology.

PMID- 30091380
TI  - Sodium nitrite augments lung S-nitrosylation and reverses chronic hypoxic
      pulmonary hypertension in juvenile rats.
AB  - Deficient nitric oxide (NO) signaling plays a critical role in the pathogenesis
      of chronic neonatal pulmonary hypertension (PHT). Physiological NO signaling is
      regulated by S-nitrosothiols (SNOs), which act both as a reservoir for NO and as
      a reversible modulator of protein function. We have previously reported that
      therapy with inhaled NO (iNO) increased peroxynitrite-mediated nitration in the
      juvenile rat lung, while having minimal reversing effects on vascular remodeling.
      We hypothesized that sodium nitrite (NaNO2) would be superior to iNO in enhancing
      lung SNOs, thereby contributing to reversal of chronic hypoxic PHT. Rat pups were
      exposed to air or hypoxia (13% O2) from postnatal days 1 to 21. Dose-response
      prevention studies were conducted from days 1-21 to determine the optimal dose of
      NaNO2. Animals then received rescue therapy with daily s.c. NaNO2 (20 mg/kg),
      vehicle or were continuously exposed to iNO (20 ppm) from days 14-21. Chronic PHT
      secondary to hypoxia was both prevented and reversed by treatment with NaNO2.
      Rescue NaNO2 increased lung NO and SNO contents to a greater extent than iNO,
      without causing nitration. Seven lung SNO-proteins up-regulated by treatment with
      NaNO2 were identified by multiplex tandem mass tag spectrometry, one of which was
      leukotriene A4 hydrolase (LTA4H). Rescue therapy with a LTA4H inhibitor, SC57461A
      (10 mg/kg/d s.c.), partially reversed chronic hypoxic PHT. We conclude that NaNO2
      was superior to iNO in increasing tissue NO and SNO generation and reversing
      chronic PHT, in part via up-regulated SNO-LTA4H.

PMID- 30091381
TI  - Novel Differences in Gene Expression and Functional Capabilities of Myofibroblast
      Populations in Idiopathic Pulmonary Fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial
      pneumonia that is characterized by excessive fibroproliferation. Key effector
      cells in IPF are myofibroblasts that are recruited from three potential sources:
      resident fibroblasts, fibrocytes and epithelial cells. We hypothesized that IPF
      myofibroblasts from different sources of origin displayed unique genetic profiles
      and distinct functional characteristics. Primary human pulmonary fibroblasts
      (normal and IPF), fibrocytes and epithelial cells were activated into
      myofibroblasts using the pro fibrotic factors TGF beta and TNF alpha. The
      resulting myofibroblasts were characterized using cell proliferation, soluble
      collagen, ELISA and contractility assays, and human fibrosis PCR arrays. Genes of
      significance were validated in whole human lung and validated by
      immunohistochemistry on human lung sections. Fibroblast-derived myofibroblasts
      exhibited the highest expression increase in pro fibrotic genes, and genes
      involved in extracellular matrix remodelling and signal transduction. Functional
      studies demonstrated that myofibroblasts derived from fibrocytes expressed most
      soluble collagen and CCL18 but were least proliferative of all myofibroblast
      progeny. Activated IPF fibroblasts displayed highest contraction and highest
      levels of CCL2 production. This study has identified novel differences in both
      gene expression and functional characteristics in different myofibroblast
      populations. Further investigation into the myofibroblast phenotype may lead to
      potential therapeutic targets in the future field of IPF research.

PMID- 30091382
TI  - Macrophages from The Upper and Lower Human Respiratory Tract Are Metabolically
      Distinct.
AB  - The function and cell surface phenotype of lung macrophages vary within the
      respiratory tract. Whether the bioenergetic profile of macrophages also differs
      depending on location within the lung is currently unknown. This study sought to
      characterize the bioenergetic profile of macrophages sampled from different
      locations within the respiratory tract at baseline and in response to ex vivo
      xenobiotic challenge. Surface macrophages recovered from healthy volunteers by
      induced sputum and by bronchial and bronchoalveolar lavage were profiled using
      extracellular flux analyses. Oxygen consumption and extracellular acidification
      rates were measured at rest and after stimulation with lipopolysaccharide (LPS),
      phorbol 12-myristate 13-acetate (PMA), or 1,2-naphthoquinone (1,2-NQ). Oxygen
      consumption and extracellular acidification rates were highly correlated for all
      macrophage samples. Induced sputum macrophages had relatively higher oxygen
      consumption and extracellular acidification rates, and were largely reliant on
      glycolysis. In contrast, bronchial fraction and bronchoalveolar macrophages
      depended more heavily on mitochondrial respiration. Bronchoalveolar macrophages
      showed elevated LPS-induced cytokine responses. Unlike their autologous
      peripheral blood monocytes, lung macrophages from any source did not display
      bioenergetic changes following LPS stimulation. The protein kinase C activator
      PMA did not affect mitochondrial respiration, while the air pollutant 1,2-NQ
      induced marked mitochondrial dysfunction in bronchoalveolar and bronchial
      fraction macrophages. The bioenergetic characteristics of macrophages from
      healthy individuals are dependent on their location within the respiratory tract.
      These findings establish a regional bioenergetic profile for macrophages from
      healthy human airways that serves as a reference for changes that occur in
      disease.

PMID- 30091384
TI  - Cancer medicine gets personal.

PMID- 30091385
TI  - Caution: choice of fixative can influence the visualization of the location of a
      transcription factor in mammalian cells.

PMID- 30091383
TI  - Assay for galactose-deficient IgA1 enables mechanistic studies with primary cells
      from IgA nephropathy patients.
AB  - AIMS: IgA nephropathy, the most common primary glomerulonephritis worldwide, is
      characterized by glomerular deposition of galactose-deficient IgA1 and elevated
      serum levels of this IgA1 glycoform. Current ELISA methods lack sensitivity to
      assess galactose deficiency using small amounts of IgA1, which limits studies in
      primary cells due to modest IgA1 production in isolated peripheral-blood
      lymphocytes. METHODS: Lectin from Helix pomatia was conjugated to biotin or
      acridinium ester and used in ELISA to detect galactose deficiency of IgA1 using
      small amounts of IgA1. RESULTS: Lectin conjugated to acridinium had an
      approximately a log-fold increased sensitivity compared with biotin-labeled
      lectin. CONCLUSIONS: The new method of using lectin from Helix pomatia conjugated
      to acridinium increased assay sensitivity, allowing future mechanistic studies
      with cultured primary cells.

PMID- 30091386
TI  - Cataract-preventing contact lens for in vivo imaging of mouse retina.
AB  - In vivo imaging of mouse retinas using two-photon or confocal laser scanning
      fluorescence microscopy is a powerful tool for time-lapse analyses of the dynamic
      movements of cell populations. However, acute and reversible opacification of the
      crystalline lenses of mouse eyes under anesthesia decreases the visibility of the
      ocular fundus. Therefore, we developed a customized contact lens for preventing
      cataract during continuous retinal imaging in anesthetized mice. This
      experimental approach will aid in the elucidation of cellular and molecular
      dynamics in the CNS under physiological and pathological conditions.

PMID- 30091387
TI  - Automating a new host-protein assay for differentiating bacterial from viral
      infection to reduce operator hands-on time.
AB  - Distinguishing bacterial from viral infections is often challenging, leading to
      antibiotic misuse, and detrimental ramifications for the patient, the healthcare
      system and society. A novel ELISA-based assay that integrates the circulating
      levels of three host-response proteins (TRAIL, IP-10 and CRP) was developed to
      assist in differentiation between bacterial and viral etiologies. We developed a
      new protocol for measuring the host-based assay biomarkers using an automated
      ELISA workstation. The automated protocol was validated and was able to reduce
      technician hands-on time by 76%, while maintaining high analytical performance.
      Following automation, the assay has been incorporated into the routine workflow
      at a pediatric department, and is performed daily on admitted and emergency
      department patients. The automation protocol reduces the overall burden on the
      hospital laboratory performing the assay. This benefit has potential to promote
      adoption of the host-based assay, facilitating timely triage of febrile patients
      and prudent use of antibiotics.

PMID- 30091388
TI  - Visualization of global RNA synthesis in a human (mini-) organ in situ by click
      chemistry.
AB  - RNA synthesis can be detected by 5-ethynyl uridine (EU) incorporation and click
      chemistry. Despite identifying a fundamental functional process, this technique
      has yet to be widely applied to complex human tissue systems. By incorporating EU
      into human hair follicle (HF) organs cultured ex vivo, nascent RNA synthesis was
      detected in situ. EU differentially incorporated across the HF epithelium.
      Interestingly, RNA synthesis did not correlate with protein synthesis,
      proliferation or epithelial progenitor cell marker expression. By treating human
      HFs with the cytotoxic cell cycle inhibitor (R)-CR8, which inhibits
      transcriptional regulators CDK7 and CDK9, it was further shown that this
      technique can be used to sensitively detect changes in global RNA synthesis in
      situ. Together, this work delineates new insights into nascent RNA synthesis
      within a human (mini)- organ and describes a novel read-out parameter that will
      enrich future ex vivo human tissue research studies.

PMID- 30091390
TI  - Animal models and virtual reality.

PMID- 30091389
TI  - Mitigation of the effect of variability in digital PCR assays through use of
      duplexed reference assays for normalization.
AB  - Digital PCR has been promoted as a technique for obtaining absolute measures of
      the amount of nucleic acid target sequence in a sample, but still lacks
      standardization in data reporting. The initial method of representing data as
      copies per microliter produced inconsistent results and made inter-assay
      comparisons difficult. Normalizing copies to amount of nucleic acid gives more
      uniform results, but factors influencing the effective concentration of nucleic
      acid in the final digital PCR assay must be considered. Using droplet digital PCR
      and previously validated reference genes duplexed with target genes, a method of
      normalization was developed to estimate the amount of input nucleic acid in
      individual assays, subsequently reporting the number of copies of target gene
      relative to this amount. Correcting for the actual amount of amplifiable nucleic
      acid present demonstrated a higher correlation between various dilutions of
      sample mRNA and allowed more accurate comparisons of digital PCR results.

PMID- 30091392
TI  - Could the use of animal models become virtually extinct?

PMID- 30091391
TI  - Suitability of melanoma FFPE samples for NGS libraries: time and quality
      thresholds for downstream molecular tests.
AB  - The use of NGS in clinical practice for precision diagnosis requires a quality
      starting material. Despite the broadly established use of formalin-fixed paraffin
      embedded (FFPE) samples in molecular testing, these usually have low-quality DNA.
      We established a method to determine the suitability of melanoma FFPE samples for
      an amplicon-based NGS custom panel analysis. DNA was extracted from unstained
      melanoma samples and wide local excision samples. Amplicon-based libraries were
      constructed and tested using time and quality parameters as variables. Time
      elapsed from sample retrieval >7 years, a quality control value > 5.63 and a DNA
      integrity value < 2.05 indicated samples were not suitable. A decision tree is
      provided with rate of samples suitable for analysis according to the combination
      of these parameters.

PMID- 30091393
TI  - Effect of swimming training on nerve morphological recovery after compressive
      injury.
AB  - OBJECTIVE: This study aims to investigate morphological alterations caused by
      partial sciatic nerve ligation (PNL) and the efficacy of a moderate-intensity
      swimming training as therapeutic strategy for nerve regeneration. METHODS: A
      number of 30 male adult mice were equally divided in control, 14 days after PNL
      (PNL 14 days), 42 days after PNL (PNL 42 days), 70 days after PNL (PNL 70 days)
      and 5-week exercise training after 7 days post-lesion (PNL trained 35 days)
      groups. PNL trained 35 days group began with a 10-min session for 3 days and this
      time was gradually increased by 10 min every three sessions until the animals had
      swum for 50 min per session. Morphoquantitative analysis was carried out to
      assess nerve regeneration in each group. RESULTS: PNL 14 days group exhibited
      less degenerating signs than PNL 42 days group, where most post-lesion
      alterations were visualized. Nerve area and minimum diameter were significantly
      lower (p < 0.05) than control group. PNL 70 days group showed a greater degree of
      regenerating fibers and similar morphometric parameters to control group. PNL
      trained 35 days demonstrated signs of regeneration, reaching control group values
      in the morphometric analysis. DISCUSSION: PNL promotes great histopathological
      changes, which became more visible at 42 post-injury days. A natural nerve
      regeneration tendency was observed throughout time, as observed in PNL 70 days
      group; nevertheless, moderate swimming training was found to be a therapeutic
      resource for nerve regeneration, accelerating such process from a
      morphoquantitative perspective. ABBREVIATIONS: ANOVA: One-way analysis of
      variance; BDNF: Brain-derived neurotrophic factor; FGF-2: Fibroblast growth
      factor 2; GDNF: Glial cell line derived neurotrophic factor; IGF: Insulin-link
      growth factor; IL-1beta: Interleukin-1beta; NGF: Neural growth factor; PBS:
      Phosphate-buffered saline; PNL: Partial sciatic nerve ligation.

PMID- 30091394
TI  - The impact of residential medication management reviews (RMMRs) on medication
      regimen complexity.
AB  - OBJECTIVES: The primary objective of this study was to investigate the impact of
      RMMRs on medication regimen complexity, as assessed by a validated measure.
      METHODS: Retrospective analysis of RMMRs pertaining to 285 aged care residents
      aged >= 65 years in Sydney, Australia. Medication regimen complexity was measured
      using the Medication Regimen Complexity Index (MRCI) at baseline, after
      pharmacists' recommendations (assuming that all of the pharmacists'
      recommendations were accepted by the General Practitioner (GP)), and after the
      actual uptake of pharmacists' recommendations by the GP. Differences in the
      regimen complexity was measured using the Wilcoxon sign rank test. RESULTS:
      Pharmacists made 764 recommendations (average 2.7 recommendations per RMMR), of
      which 569 (74.5%) were accepted by GPs. The median MRCI at baseline in the sample
      was 25.5 (IQR = 19.0-32.5). No statistically significant differences were
      demonstrated in the MRCI scores after pharmacists' recommendations (p = 0.53) or
      after GPs' acceptance of these recommendations (p = 0.07) compared to the
      baseline. CONCLUSION: Our study revealed high acceptance of pharmacists'
      recommendations by GPs. This suggests that RMMRs are useful for identifying and
      resolving drug-related issues among residents of ACFs. However, our study failed
      to show a significant effect of RMMRs in reducing the medication regimen
      complexity, as measured by the MRCI. Further studies are needed to establish the
      association of medication regimen complexity and clinical outcomes in residents
      of ACFs.

PMID- 30091395
TI  - Novel GPC3-binding WS2-Ga3+-PEG-peptide nanosheets for in vivo bimodal imaging
      guided photothermal therapy.
AB  - AIM: The diagnosis and treatment of hepatocarcinoma (HCC) is believed to be
      improved due to the development of specific targeting probes by molecular imaging
      methods. GPC3, which is a hepatocellular carcinoma (HCC)-specific tumor marker,
      anchors at most HCC cells. To target this cell membrane protein, we developed a
      novel nanoparticle by conjugating WS2-Ga3+-PEG and a short peptide with favorable
      specificity and affinity to the GPC3 protein. MATERIALS & METHODS: In in vitro
      assay, several physical properties of the novel probe were evaluated. In in vivo
      assay, MRI, photoacoustic imaging and photothermal therapy were performed in the
      subcutaneous HepG2-bearing mice with the novel probe. RESULTS & CONCLUSION: The
      effect of imaging and photothermal therapy was significant. We revealed that the
      novel nanosheet WS2-Ga3+-PEG-peptide is promising to detect and treat HCC
      expressing GPC3.

PMID- 30091396
TI  - Automaticity and cognitive control: Effects of cognitive load on cue-controlled
      reward choice.
AB  - The extent to which human outcome-response (O-R) priming effects are automatic or
      under cognitive control is currently unclear. Two experiments tested the effect
      of cognitive load on O-R priming to shed further light on the debate. In
      Experiment 1, two instrumental responses earned beer and chocolate points in an
      instrumental training phase. Instrumental response choice was then tested in the
      presence of beer, chocolate, and neutral stimuli. On test, a Reversal instruction
      group was told that the stimuli signalled which response would not be rewarded.
      The transfer test was also conducted under either minimal (No Load) or
      considerable (Load) cognitive load. The Non-Reversal groups showed O-R priming
      effects, where the reward cues increased the instrumental responses that had
      previously produced those outcomes, relative to the neutral stimulus. This effect
      was observed even under cognitive load. The Reversal No Load group demonstrated a
      reversed effect, where response choice was biased towards the response that was
      most likely to be rewarded according to the instruction. Most importantly,
      response choice was at chance in the Reversal Load condition. In Experiment 2,
      cognitive load abolished the sensitivity to outcome devaluation that was
      otherwise seen when multiple outcomes and responses were cued on test.
      Collectively, the results demonstrate that complex O-R priming effects are
      sensitive to cognitive load, whereas the very simple, standard O-R priming effect
      is more robust.

PMID- 30091398
TI  - Chinese version - Jubliee issue.

PMID- 30091397
TI  - Is the framing effect a framing affect?
AB  - Over the past 30 years, researchers have shown that human choices are highly
      sensitive to the ways in which alternatives are presented. For example, when
      individuals face a choice between a sure and a risky option, their willingness to
      take risks varies depending on whether the alternatives are framed in terms of
      gain or loss. The current major hypothesis that explains such a framing effect
      predicts that compared with an equivalent risky option, sure gains are
      emotionally attractive and sure losses are emotionally aversive. Using a
      behavioural paradigm, the main objective of the current study was to
      experimentally observe the extent to which the emotional attraction to sure gains
      and aversion to sure losses are at the core of framing susceptibility. First, our
      results showed that, as the literature suggests, the emotional attraction to sure
      gains and aversion to sure losses underpin the framing effect. Second, our
      results showed that methodological factors moderated the role of these emotional
      mechanisms in the framing effect. Implications and directions for future studies
      are discussed.

PMID- 30091400
TI  - Academic and Scientific Authorship Practices: A Survey Among South African
      Researchers.
AB  - Empirical studies of authorship practices in high-income countries have been
      conducted, while research on this issue is scarce in low- and middle-income
      countries. A survey was conducted among South African researchers who have
      published in peer-reviewed journals, to explore their understanding of and
      ability to apply academic authorship criteria. A total of 967 researchers
      participated in the survey; 88% of respondents had knowledge of academic
      authorship criteria, while only 52% found it easy to apply the criteria. More
      respondents experienced disagreement regarding who qualifies for coauthorship
      compared with authorship order (59% vs. 48%). Disagreement was mostly linked to
      different ways of valuing or measuring contributions. Level of agreement with
      academic authorship criteria was higher than the perceived ability to apply the
      criteria.

PMID- 30091401
TI  - Cryptogenic and non-cryptogenic liver abscess: A retrospective analysis of 178
      cases revealed distinct characteristics.
AB  - Objective To enhance theoretical support of pyogenic liver abscess (PLA)
      treatment by comparing characteristics of patients with either PLA with an
      identified infectious origin (non-cryptogenic) or PLA with no obvious underlying
      cause (cryptogenic). Methods This retrospective study included all first episodes
      of PLA in adults admitted to a tertiary hospital between 2009 and 2016. Relevant
      clinical data were collected for patients with cryptogenic or non-cryptogenic PLA
      and compared across a number of characteristics. Results In all, 178 patients
      were included: 111 cases (62.4%) of cryptogenic PLA, and 67 cases (37.6%) of non
      cryptogenic PLA. Diabetes mellitus was significantly more prevalent in patients
      with cryptogenic PLA than those with non-cryptogenic PLA. The proportion of
      multidrug resistance/poly-microbial infection was significantly lower and
      Klebsiella pneumoniae infection was significantly higher in the cryptogenic
      versus non-cryptogenic PLA group. Metastatic infection occurred in four patients
      with cryptogenic PLA only, and all had diabetes and K. pneumoniae infection.
      Multivariate logistic regression analysis revealed that male sex, diabetes and K.
      pneumoniae were independent predictors for cryptogenic PLA. Conclusions
      Cryptogenic and non-cryptogenic PLA have distinctly different characteristics,
      suggesting a potential need for different treatment approaches.

PMID- 30091402
TI  - Insights into the Noncoding RNA-encoded Peptides.
AB  - BACKGROUND: Considerable evidence has indicated that most noncoding RNA (ncRNA)
      transcripts act directly as functional RNAs rather than as encoded peptides.
      However, a recent study of ribosome occupancy reported that many large intergenic
      ncRNAs (lincRNAs) are bound by ribosomes, raising the possibility that they are
      translated into proteins. These lincRNAs contain either Internal Ribosomal Entry
      Sites (IRES) or short Open Reading Frames (sORFs), and other translation
      elements, which can be translated into peptides with physiological functions.
      CONCLUSION: This review discusses three major types of ncRNA-encoded peptides
      (ncPEPs). First, microRNA(miRNA)-encoded peptides (miPEPs) are translated from
      their primary transcripts of miRNA genes and can promote the development of plant
      roots. Second, a long ncRNA(lncRNA) containing sORF encodes a 90 residues long
      regulatory peptide. Upon the amino acid response, the lncRNA-encoded peptide
      reduces the activity of mammalian Target Rapamycin complex 1 (mTORC1) and
      promotes muscle regeneration. Third, a circular RNA (circRNA) of the Na+/Ca2+
      exchanger gene 1 (NCX1) exon 2 transcript encodes a truncated NCX1 protein
      exhibiting the Na+/Ca2+ exchange activity. It is also of worth noting that the
      majority of ncRNAs is not translated. This review summarizes the current
      understanding of the translatability of ncRNAs and the functions of ncPEPs in
      cellular processes, which may provide novel insights into the roles of ncPEPs.

PMID- 30091399
TI  - Pathogenesis of medication-related osteonecrosis of the jaw: a comparative study
      of in vivo and in vitro trials.
AB  - Objective This study was performed to determine whether the results of prevailing
      in vivo and in vitro studies offer a reliable model for investigation of
      medication-related osteonecrosis of the jaw (MRONJ). Methods Embase, Medline, and
      the Cochrane Library were searched for articles published from September 2003 to
      June 2017 involving experimental approaches to the pathogenesis of MRONJ. In vivo
      and in vitro trials were analyzed with respect to the scientific question, study
      design, methodology, and results. Results Of 139 studies, 87, 46, and 6 conducted
      in vivo, in vitro, and both in vivo and in vitro experiments, respectively. Rats,
      mice, dogs, minipigs, sheep, and rabbits were the preferred animal models used.
      Osteoblasts, osteoclasts, fibroblasts, keratinocytes, macrophages, and human
      umbilical vein endothelial cells were the preferred cell types. Zoledronate,
      alendronate, ibandronate, and risedronate were the most frequent bisphosphonates
      used. MRONJ was most reliably induced in minipigs because of the close
      relationship with human bone physiology. In vitro studies showed that reduced
      viability, growth, and migration of cells in the bone and soft tissues were
      causative for MRONJ. Other than exposed jawbone after tooth extraction, no
      reliable cofactors were found. Conclusion The minipig is the most suitable animal
      model for MRONJ.

PMID- 30091403
TI  - VLP Production from Recombinant L1/L2 HPV-16 Protein Expressed in Pichia
      Pastoris.
AB  - BACKGROUND: Human papillomavirus 16 is considered a causative agent of genital
      cancers. Since there is no decisive treatment, the only approach is vaccination
      of high-risk group. OBJECTIVE: This study aimed to produce a chimeric L1/L2
      protein in Pichia Pastoris system. METHOD: To develop VLPs of chimeric L1/L2
      protein HPV-16, first, a cross-neutralizing epitope of HPV-16 L2 gene was
      inserted into L1 HPV-16 gene. Then the chimeric L1/L2 HPV-16 was inserted in
      pPICZA plasmid and expressed in Pichia pastoris (P. pastoris). The final
      purification of VLPs was carried out by ultra-centrifugation (130000 g) using 10
      40% sucrose density gradient for 4 h at 4  degrees C. The SDS-PAGE and western
      blot assay was carried out for L1-HPV-16 and L2-HPV- 16 proteins separately.
      Amount of 55ng of the purified VLPs was coated to the wells of ELISA for
      detection of L1 HPV-16 antibody and L2-HPV-16 antibody by ELISA test separately
      using commercial L1-HPV-16 and L2-HPV-16 antibodies. The sera of 16 patients
      positive for HPV-16 and 85 sera negative for HPV infections were tested for
      detection of HPV-16 antibody by ELISA test and the results were compared with
      commercial test kit. RESULTS: The formation and purified VLPs were observed by
      TEM and AFM. The result of purified VLPs by SDS-PAGE showed a band of 60 KD and
      confirmed by western blot assay. The results of ELISA for detection of L1-HPV-16
      antibody and L2 -HPV-16 antibody showed positive reaction which displayed similar
      sensitivity with commercial test kit. CONCLUSION: The present study will pave the
      way for producing recombinant pan-HPV vaccine.

PMID- 30091404
TI  - Aquacultural, Nutritional and Therapeutic Biology of Delicious Seeds of Euryale
      ferox Salisb. : A Minireview.
AB  - BACKGROUND: Euryale ferox Salisb. (Makhana) is a rooted macro-hydrophyte, grown
      as a crop in north Bihar wetlands, India. Makhana refers to yummy pops prepared
      through mechanical smacking of the baked seeds of E. ferox. New techniques have
      been evolved to produce pops from seeds at a brisk pace. OBJECTIVE: It is
      specially associated with marital rituals possibly in view of its spermatogenic
      properties. It has a high amino acid index but a low glycemic value. The plant
      carries medicinal values against cardiovascular and diabetes-related diseases.
      Makhana pops with a high volume to mass ratio, is developed as a reliable system
      for drug delivery in the recent times. RESULTS: There is a fair prospect of
      raising multi-faceted industry based on Makhana culture, harvest, post-harvest
      safety, preparation of pops and various types of food products therefrom and
      marketing in areas where water-logging is considered as a curse. It may generate
      employment and strengthen regional economy propping check on population migration
      primarily due to non-employment and poverty. CONCLUSION: Active research is
      required to harness this macro-hydrophyte along with co-culture of compatible
      fish varieties and other hydrophytes into a sustainable livelihood and economic
      prosperity.

PMID- 30091405
TI  - Manipulating intracellular Ca2+ signals to stimulate therapeutic angiogenesis in
      cardiovascular disorders.
AB  - Endothelial progenitor cells (EPCs) are mobilized in peripheral blood to rescue
      blood perfusion in ischemic tissues. Several approaches were, therefore, designed
      to inject autologous EPCs and induce therapeutic angiogenesis in patients
      affected by cardiovascular disorders. Endothelial colony forming cells (ECFCs)
      represent the only truly endothelial precursor and are regarded as the most
      suitable substrate for cell based therapy of ischemic diseases. Intracellular
      Ca2+ signalling drives ECFC proliferation, migration, homing and neovessel
      formation. Vascular endothelial growth factor (VEGF) triggers repetitive
      oscillations in intracellular Ca2+ concentration ([Ca2+]i) in peripheral blood-
      and umbilical cord blood-derived ECFCs by initiating a dynamic interplay between
      inositol-1,4,5-trisphosphate (InsP3)-dependent Ca2+ release and store-operated
      Ca2+ entry (SOCE). SOCE, in turn, is mediated by Stim1, Orai1 and Transient
      Receptor Potential (TRP) Canonical 1 (TRPC1). Intriguingly, intracellular Ca2+
      oscillations are triggered by TRPC3 in umbilical cord blood-derived ECFCs, which
      display higher proliferative potential. Additionally, stromal cell-derived factor
      1a (SDF-1a) triggers a biphasic increase in [Ca2+]i in ECFCs which is mediated by
      InsP3 receptors (InsP3Rs) and SOCE. Finally, arachidonic acid (AA) and nicotinic
      acid adenine dinucleotide phosphate (NAADP) stimulate ECFC proliferation by
      stimulating two-pore channel 1 (TPC1), thereby promoting Ca2+ release from the
      endolysosomal Ca2+ compartment. AA-evoked Ca2+ signals are further supported by
      InsP3Rs and TRP Vanilloid 4 (TRPV4). In this article, we describe how genetic
      manipulation of the Ca2+ toolkit (i.e. TRPC3, SOCE, TPC1) endowed to circulating
      ECFCs could rejuvenate or restore their reparative phenotype for therapeutic
      angiogenesis purposes.

PMID- 30091406
TI  - Role of NLRP-3 Inflammasome in Hypertension: a Potential Therapeutic Target.
AB  - Background Hypertension is a multifactorial and chronic cardiovascular condition
      whose complications are responsible for worldwide morbidity and mortality. An
      increasing body of experimental data, recognize low-grade inflammation as a basic
      process in hypertension onset and development since there is a strong
      contribution of both the innate and the adaptive immune system according to the
      so-called Danger-Model. In this contest, NLRP3 inflammasome represents a key
      signaling platform as demonstrated by its implication in several hypertension
      associated conditions, such as vascular smooth muscle remodeling and
      proliferation. This intracellular receptor is activated by Pathogen-associated
      molecular pattern molecules/damage-associated molecular pattern molecules signals
      and its mechanism of action converges on the final production of caspase-1 and,
      consequently, of the pro-inflammatory cytokines IL-1beta and IL-18. Objective The
      aim of the present work was to point the role of the NLRP3 inflammasome complex
      in the hypertensive pathology and to describe it as a new potential therapeutic
      target. Method A systematic review of the literature data related to NLRP3 and
      hypertension correlation has been performed. Results Numerous and well-designed
      experiments demonstrate that the inflammasome plays a crucial role in essential
      and high-salt dependent hypertension, as well as in preeclampsia, in pulmonary
      hypertension, and in its related secondary disorders; its mechanism includes both
      a central nervous and a peripheral modulation of the inflammatory pathways. To
      date, research is trying to design inflammasome antagonists or equivalent
      inhibition strategies. Conclusion The inflammasome represents a leading promoter
      of hypertensive inflammation opening new perspective in the field of the clinical
      approach in this pathology.

PMID- 30091407
TI  - Validation of calculated globulin (CG) as a screening test for antibody
      deficiency in an Italian University Hospital.
AB  - Morbidity and mortality of primary and secondary antibody deficiencies (AD) are
      frequently associated with diagnostic delays. These could be avoided by a
      combination of factors including a widespread and effective development in
      screening tests. Calculated globulin (CG), derived from the difference between
      serum total protein and albumin levels, reflects immunoglobulin serum levels and
      has shown to have a predictive value in the early diagnosis of antibody
      deficiencies. This study investigated the possibility to use low levels of CG to
      detect antibody deficiency in an Italian University Hospital. First, we conducted
      an analysis of anonymized adult samples collected at our biochemistry laboratory
      with a range of calculated globulin levels from 15 to 22 g/l. A CG cut-off of 19
      g/l detected subjects with IgG lower than 600 mg/dl with a sensitivity of 70% and
      a specificity of 75%. To further verify the clinical usefulness of CG, we
      retrospectively evaluated the relationship between CG values and serum IgG levels
      in 38 patients diagnosed with CVID at our Institution. Using a CG cut-off of 19
      g/l we detected antibody deficiency in 97.3% (37/38) of the subjects present in
      our cohort. Finally, we chose a CG value of 19 g/l as cut-off for a prospective
      AD screening program. The results of this study show that a screening CG test can
      be used as a tool to reduce diagnostic delays, improve long-term prognosis and
      reduce the healthcare costs of antibody deficiency.

PMID- 30091408
TI  - Lipid Droplets Breakdown: Adipose Triglyceride Lipase Leads the Way.

PMID- 30091409
TI  - Role of Neuropeptides in the Regulation of the Insect Immune System - Current
      Knowledge and Perspectives.
AB  - Despite much research on the insect immune system, hormonal regulation of its
      activity is not well-understood. Previous research on insect neuroendocrinology
      suggests that neuropeptides may play an important role in the regulation of the
      insect immune system. Especially recent studies dealing for example with
      adipokinetic hormones, bursicon or insulin-like peptides provided deeper insights
      on this issue showing that neuropeptides can modulate various aspects of insect
      immune responses, both at the molecular and cellular level. The presented review
      summarizes the current knowledge about the role of neuropeptides regulating the
      insect immune system activity. Based on structural and functional homology of
      some vertebrate and insect neuropeptide families, several propositions of insect
      neuropeptides that might also possess immunotropic activities, but have not been
      examined for this aspect, are discussed.

PMID- 30091410
TI  - Post-translational N-terminal Arginylation of Protein Fragments: A Pivotal Portal
      to Proteolysis.
AB  - The majority of tRNA studies has focused on tRNA molecules as pivotal player in
      the fundamental process of protein synthesis. Mounting studies have unveiled
      further functions for tRNA beyond protein synthesis, including non-ribosomal
      amino acid transfer, and regulation of targeted proteolysis. Post-translational N
      terminal arginylation of protein fragments, a non-ribosomal amino acid transfer,
      is one of the crucial ways by which tRNA participates in various protein
      degradation trajectories and influences global cellular functions. Previous
      studies demonstrated a role of arginylation by arginyltransferases (ATEs) in
      protein degradation, autophagy, and cell death in mammalian cells. Notably,
      recent investigations in plants have revealed some of the crucial aspects
      regarding the biochemical nature of Nterminal arginylation and some of its
      physiological roles. Herein, we review some of the key data on Nterminal
      arginylation of protein fragments with respect to targeted proteolysis in
      mammalian cells. Future mechanistic studies using state of the art approaches and
      physiologically-relevant cellular models are warranted to enhance our molecular
      understanding of this important yet enigmatic protein modification.

PMID- 30091411
TI  - Heat-Loving beta-Galactosidases from Cultured and Uncultured Microorganisms.
AB  - beta-galactosidases (EC.3.2.1.23), which hydrolyze lactose to glucose and
      galactose, have two main applications in the food industry: the production of low
      lactose milk and dairy goods for lactose intolerant people, and the generation of
      galacto-oligosaccharides by transgalactosylation reactions. Due to their
      thermostability, beta-galactosidases from thermophilic microorganisms are very
      interesting for industrial processes, as high temperatures can increase the
      initial productivity of the enzyme, provide higher solubility of substrates, and
      prevent microbial contamination. In the past, it was necessary to cultivate and
      grow thermophilic microorganisms to discover novel thermozymes, but the
      development of metagenomic techniques has allowed researchers to access the
      genomic potential of uncultivated microbes and their enzymes. The present review
      gives a brief outline of thermophilic beta-galactosidases, with a special focus
      on those obtained through metagenomics. Additionally, the sequences of beta
      galactosidases found in some public metagenomes from hot springs were studied and
      compared to other known thermostable beta-galactosidases.

PMID- 30091412
TI  - Roles of Talin2 in Traction Force Generation, Tumor Metastasis and Cardiovascular
      Integrity.
AB  - There are two vertebrate talin genes, TLN1 and TLN2, which encode talin1 and
      talin2. Talin1 governs integrin activation, thus regulating focal adhesion (FA)
      assembly, cell migration and invasion, but the biological function of talin2
      remains to be elucidated and not too long ago talin2 was presumed to function
      redundantly with talin1. Recent studies have shown distinct differences between
      talin2 and talin1. The promoter of TLN2 is different from that of TLN1 in their
      size and binding to different transcription factors. Talin2 has a higher affinity
      to beta -integrins than talin1. Talin2 regulates traction force generation, focal
      adhesion dynamics and invadopodium formation, thus controlling tumor cell
      migration, invasion and metastasis. Also, talin2 is enriched in the myotendinous
      junction (MTJ) in striated muscle, costameres and intercalated disks (ICDs) of
      cardiac myofibrils, and atherosclerotic plaques of blood vessels, thus regulating
      cardiovascular integrity. In this review, we discuss the differences between
      talin1 and talin2, in genome, protein expression pattern, affinity with
      integrins, traction force generation, and provide a glance at the roles of talin2
      in cancer cell invasion and cardiovascular function.

PMID- 30091413
TI  - Application of Machine Learning Approaches for the design and study of anticancer
      drugs.
AB  - BACKGROUND: Globally the number of cancer patients and deaths are continuing to
      increase yearly, and cancer has, therefore, become one of the world's highest
      causes of morbidity and mortality. In recent years, the study of anticancer drugs
      has become one of the most popular medical topics. OBJECTIVE: In this review, in
      order to study the application of machine learning in predicting anticancer drugs
      activity, some machine learning approaches such as Linear Discriminant Analysis
      (LDA), Principal components analysis (PCA), Support Vector Machine (SVM), Random
      forest (RF), k-Nearest Neighbor (kNN), and Naive Bayes (NB) were selected, and
      the examples of their applications in anticancer drugs design are listed.
      RESULTS: Machine learning contributes a lot to anticancer drugs design and helps
      researchers by saving time and is cost effective. However, it can only be an
      assisting tool for drug design. CONCLUSIONS: This paper introduces the
      application of machine learning approaches in anticancer drug design. Many
      examples of success in identification and prediction in the area of anticancer
      drugs activity prediction are discussed, and the anticancer drugs research is
      still in active progress. Moreover, the merits of some web servers related to
      anticancer drugs are mentioned.

PMID- 30091414
TI  - Advances in Discovery of PDE10A Inhibitors for CNS-Related Disorders. Part 1:
      Overview of the Chemical and Biological Research.
AB  - Phosphodiesterase 10A (PDE10A) is a double substrate enzyme that hydrolyzes
      second messenger molecules such as cyclic-3',5'-adenosine monophosphate (cAMP)
      and cyclic-3',5'-guanosine monophosphate (cGMP). Through this process, PDE10A
      controls intracellular signaling pathways in the mammalian brain and peripheral
      tissues. Pharmacological, biochemical, and anatomical data suggest that disorders
      in the second messenger system mediated by PDE10A may contribute to impairments
      in the central nervous system (CNS) function, including cognitive deficits as
      well as disturbances of behavior, emotion processing, and movement. This review
      provides a detailed description of PDE10A and the recent advances in the design
      of selective PDE10A inhibitors. The results of preclinical studies regarding the
      potential utility of PDE10A inhibitors for the treatment of CNS-related
      disorders, such as schizophrenia as well as Huntington's and Parkinson's diseases
      are also summarized.

PMID- 30091415
TI  - Chemistry And Pharmacological Activities Of Biginelli Product- A Brief Overview.
AB  - Dihydropyrimidinones are extremely advantageous small sized molecules owning
      adaptable pharmaceutical properties. With a molecular formula C4H6N2O, they hold
      a wide range of biological activities. It is a heterocyclic moiety having two N
      atoms at positions 1 and 3. They are derivatives of pyrimidine containing an
      additional ketone group. They have inspired development of a wide range of
      synthetic methods for preparation and chemical transformations. Taking into
      consideration their structural similarity and involvement with DNA and RNA, they
      have become very imperative in the world of synthetic organic chemistry. Aryl
      substituted moieties and their derivatives are significant class of substances in
      medicinal and organic chemistry. Many alkaloids from natural marine sources
      comprising dihydropyrimidinones core have been isolated which possess fascinating
      biological properties. Intensive explorations have been carried out on these
      compounds because they possess close similitude to clinically used nifedipine,
      nicardipine etc. which are also Biginelli product analogues. Due to the
      interesting pharmacological properties associated with the privileged DHPM
      structures, the Biginelli reaction and related procedures have received
      increasing attention in recent years.

PMID- 30091416
TI  - The Role of Vascular Endothelial Growth Factor in Systemic Sclerosis.
AB  - The pathological hallmarks of Systemic sclerosis (SSc) constitute an inter
      related triad of autoimmunity, vasculopathy and tissue remodeling. Many signaling
      mediators have been implicated in SSc pathology; most focusing on individual
      components of this pathogenic triad and current treatment paradigms tend to
      approach management of such as distinct entities. The present review shall
      examine the role of vascular endothelial growth factor (VEGF) in SSc
      pathogenesis. We shall outline potential mechanisms whereby differential vascular
      endothelial growth factor-A (VEGF-A) isoform expression (through conventional and
      alternative VEGF-A splicing,) may influence the relevant burden of vasculopathy
      and fibrosis offering novel insight into clinical heterogeneity and disease
      progression in SSc. Emerging therapeutic approaches targeting VEGF signaling
      pathways might play an important role in the management of SSc, and differential
      VEGF-A splice isoform expression may provide a tool for personalized medicine
      approaches to disease management.

PMID- 30091417
TI  - Preclinical Studies on Biomaterial Scaffold use in Knee Ligament Regeneration: A
      Systematic Review.
AB  - BACKGROUND: Knee joint trauma may result in damage of the intra-articular
      ligaments, with rupture of the anterior cruciate ligament (ACL) a common and
      troublesome injury due to poor capabilities for spontaneous regeneration.
      Autograft and allograft surgical reconstructions are the mainstay of treatment,
      but have associated risks of failure, therefore tissue-engineering techniques
      aiming to regenerate the native ACL are being researched as a potential
      alternative treatment. OBJECTIVES: This article aims to review the current
      evidence produced by ex vivo and in vivo studies investigating biomaterial
      scaffolding and mesenchymal stem cell (MSC) techniques in orthopaedic tissue
      engineering of ACL injuries. METHODS: Databases searched were Ovid MEDLINE,
      Cochrane Library, Embase, Elsevier Scopus, Web of Science and NCBI PubMed, with
      search terms 'ligament', 'scaffold', 'mesenchymal stem cell' and 'tissue
      engineering'. RESULTS: 1132 articles were identified, with 19 articles suitable
      for review inclusion. Of the eligible studies, 10 used biologic scaffold
      material, 6 used synthetic constructs, and hybrid scaffolds were employed in the
      remaining 3 studies. CONCLUSIONS: A large amount of preclinical evidence for
      viability of MSC seeded biomaterial scaffolds in ACL regeneration exists. Studies
      show that with stimulation, MSCs adhere and proliferate well on various scaffold
      materials ranging from silk to engineered polymers. Hybrid scaffolds are
      particularly promising, and with further research, the best features from strong
      natural substances such as silk, and biologically inert synthetic materials could
      be combined. Currently, there are few plans to begin human clinical trials, but
      preclinical studies are moving into larger animal models.

PMID- 30091418
TI  - Journey Describing the Cytotoxic Potential of Withanolides: A Patent Review.
AB  - Withanolides are C-28 ergostane steroids known to demonstrate some very
      interesting therapeutic properties. Numerous withanolides have been isolated from
      a variety of different plant species and can be employed to treat various types
      of cancers. Withanolides are indeed capable of demonstrating excellent
      anticancer, anti-inflammatory, and neuroprotective activities. Additionally,
      libraries of prepared withaferin A analogs incorporating an acyl, sulphate, amide
      and aldehyde functionality have demonstrated the most potential response. It is
      of particular interest to note that an acetyl group at either C-4, C-19 or C-27
      enhances the anticancer effects. Since the majority of natural withanolides
      reported in patents are classified as "Type-A", it is our opinion that there
      should now be a focus on developing "Type-B" withanolides and an investigation
      into their various therapeutic applications. Moreover, very little real
      innovation in synthetic methodologies has been reported which opens up huge
      possibilities for novel synthetic methodologies to be developed for the
      production of larger libraries new withanolides and their analogs to incorporate
      chemical diversity. In addition, since withanolides have the capability to
      conjugate with other anticancer compounds, this should encourage scientists to
      prepare lead compounds in cancer drug discovery.

PMID- 30091419
TI  - Diabetes Mellitus to Neurodegenerative Disorders: Is Oxidative Stress Fueling the
      Flame?
AB  - BACKGROUND & OBJECTIVE: Diabetes and neurodegenerative diseases (ND) are
      progressive morbidities and represent a major public health burden. A growing
      body of evidence points towards the comorbidity of diabetes and NDs with a
      possible exacerbation of latter by former. Considering the high prevalence of
      both morbidities in aging world population, even a modest impact of diabetes on
      NDs could lead to significant public health implications. Several hypotheses and
      mechanistic evidence were proposed linking altered glucose metabolism to the risk
      of progressive dementia. Unregulated production of reactive oxygen species (ROS)
      and resultant oxidative stress (OS) are the common features of diabetes as well
      as NDs. CONCLUSION: This review explores the concept of altered glucose metabolic
      pathways leading to ROS increase and its possible link to NDs, with a special
      emphasis on Alzheimer's diseases (AD). We also discuss the detailed mechanistic
      link between hyperglycemia, ROS generation, and neurodegeneration to highlight
      potential therapeutic avenues for better prevention and treatment.

PMID- 30091421
TI  - Correction: DARING-B: discontinuation of effective entecavir or tenofovir
      disoproxil fumarate long-term therapy before HBsAg loss in non-cirrhotic HBeAg
      negative chronic hepatitis B.

PMID- 30091420
TI  - Retrosigmoid Versus Traditional Ileal Conduit for Urinary Diversion After Radical
      Cystectomy.
AB  - BACKGROUND: Ureteroileal anastomotic stricture (UAS) after ileal conduit
      diversion occurs in a non-negligible proportion of patients undergoing radical
      cystectomy (RC). Surgical techniques aimed at preventing this potential
      complication are sought. OBJECTIVE: To describe our surgical technique of
      retrosigmoid ileal conduit, and to assess perioperative outcomes and
      postoperative complications with a focus on UAS rate. DESIGN, SETTING, AND
      PARTICIPANTS: A prospective single-centre, single-surgeon cohort of 67
      consecutive patients undergoing open RC with ileal conduit urinary diversion
      between July 2013 and April 2017 was analysed. A study group of 30 patients
      receiving retrosigmoid ileal conduit was compared with a control group of 37
      patients receiving standard Wallace ileal conduit. SURGICAL PROCEDURE:
      Retrosigmoid versus Wallace ileal conduit diversion after open RC. MEASUREMENTS:
      Operative room (OR) time, estimated blood loss (EBL), transfusion rate, and 90-d
      postoperative complications were recorded and compared between the two groups. In
      particular, rate of UAS, defined as upper collecting system dilatation requiring
      endourological or surgical management, was assessed and compared. RESULTS AND
      LIMITATIONS: The two groups were comparable with regard to all demographic,
      clinical, and pathological variables. No differences were observed in terms of OR
      time (p=0.35), EBL (p=0.12), and transfusion rate (p=0.81). Ninety-day
      postoperative complications were observed in 11 (36.7%) patients who underwent a
      retrosigmoid ileal conduit and 20 (54.1%) patients who received a traditional
      ileal conduit (p=0.32). Major complications (grade 3-4) were observed in three
      (10%) cases in the former group and in 12 (32.4%) cases in the latter group
      (p=0.08). Mean (standard deviation) follow-up time was 10.8+/-4.0 mo in the study
      group and 27.5+/-9.5 mo in the control group (p<0.001). No single case of UAS was
      observed in the study group, whereas six (16.2%) cases of UAS occurred in the
      control group (p=0.02). The main limitation is a nonrandomised comparison of a
      relatively small cohort with short-term follow-up. CONCLUSIONS: In our study, we
      observed a significantly reduced rate of UAS and no increase in postoperative
      complications with the retrosigmoid ileal conduit diversion compared with
      standard Wallace ileal conduit diversion after open RC. PATIENT SUMMARY: We
      describe our surgical technique of retrosigmoid ileal conduit as urinary
      diversion after open radical cystectomy. Compared with traditional techniques,
      our technique for ileal conduit was found to be safe and reduce the risk of
      ureteric strictures.

PMID- 30091422
TI  - 3D printing of strontium-doped hydroxyapatite based composite scaffolds for
      repairing critical-sized rabbit calvarial defects.
AB  - In this study, strontium substituted hydroxyapatite (Sr-HAP) was synthesized
      using collagen type I and citrate as bi-templates and the obtained nanoparticles
      with high similarity to natural bone minerals were made into composite scaffolds
      with interconnected porous structure using a three-dimensional (3D) printing
      technique. A calcium deficient structure of HAP phase was caused by doping Sr
      which was verified by Fourier transform infrared, x-ray diffractometer, scanning
      electron microscopy and transmission electron microscopy. The Sr/(Sr + Ca) molar
      ratio in Sr-HAP nanoparticles was 5.8% estimated by EDX. Furthermore, both 3D
      printed scaffolds made of Sr-HAP and HAP had uniform porous structure and
      porosity of about 60%. Cell culturing indicated that MC3T3-E1 cells could adhere
      on the surface of the scaffolds and the strontium substitution could enhance cell
      adhesion, proliferation and alkaline phosphatase activity. The printed composite
      scaffolds were used to repair critical-sized rabbit calvarial defects with a
      diameter of 15 mm. The results showed that the Sr-HAP scaffolds had better
      osteogenic capability and stimulated more new bone formation within 12 weeks. It
      was suggested that these printed Sr-HAP composite scaffolds possessed high
      potential as candidates in the application of bone augmentation and regeneration.

PMID- 30091423
TI  - Differences in nonlinear heart dynamics during rest and exercise and for
      different training.
AB  - OBJECTIVE: In this work we want to analyze differences in nonlinear properties
      between rest and exercise and also to study the permanent effects of physical
      exercise on heart rate dynamics. APPROACH: It has been shown that physical
      exercise alters heart dynamics by increasing heart rate and decreasing
      variability, modifying spectral power and linear correlations, etc. We
      hypothesize that physical exercise should also reduce nonlinearity in the
      heartbeat time series. To quantify nonlinearity in the heartbeat time series, we
      use an index of nonlinearity recently proposed by Bernaola et al based on
      correlations of the magnitude time series. MAIN RESULTS: Our results confirm our
      initial hypothesis of loss of nonlinearity during physical exercise. Moreover,
      regarding the permanent effects of physical exercise on heart rate dynamics, we
      also obtain that aerobic physical training tends to increase nonlinearity in
      heart dynamics during rest. SIGNIFICANCE: It is well-known that heart dynamics
      are controlled by complex interactions between the sympathetic and
      parasympathetic branches of the autonomic nervous system. Moreover, these two
      branches act in a competing way, resulting in a clear parasympathetic withdrawal
      and sympathetic activation during physical exercise. We associate these
      interactions during physical exercise with a drastic loss of nonlinear properties
      in the heartbeat time series, revealing the importance of nonlinearity measures
      in the study of complex systems.

PMID- 30091424
TI  - Inhibition of Epidermal Growth Factor Receptor (EGFR) Reduces Lipopolysaccharide
      (LPS)-Induced Activation and Inflammatory Cytokines in Hepatic Stellate Cells In
      Vitro.
AB  - BACKGROUND Epidermal growth factor receptor (EGFR) expression is associated with
      hepatic fibrogenesis. Activated hepatic stellate cells (HSCs) release
      inflammatory cytokines and extracellular matrix (ECM). The aim of this in vitro
      study was to investigate HSCs, activated by lipopolysaccharide (LPS), and the
      role of EGFR using the small molecule EGFR inhibitor, AG1478, and using knockdown
      of the EGFR gene using small interfering RNA (siRNA) cell transfection. MATERIAL
      AND METHODS HSCs, isolated from male Sprague-Dawley rats, were cultured and
      treated with and without LPS (100 ng/mL), with and without AG1478 (2.5 MUM and
      5.0 MUM) Cell survival and proliferation were studied using an MTT assay. Western
      blot was used to measure levels of tumor necrosis factor (TNF)-alpha, interleukin
      (IL)-6, IkappaBalpha, cytoplasm and nuclear NFkappaB and EGFR in the cell lysates
      before and after small interfering RNA (siRNA) transfection. Quantitative reverse
      transcription polymerase chain reaction (RT-qPCR) was used to measure the mRNA
      levels of transforming growth factor (TGF)-beta, Col-1, and alpha-smooth muscle
      actin (SMA). The Toll-like receptor 4 (TLR4) antagonist TAK-242 and the selective
      c-Src inhibitor, PP2 in LPS induced-EGFR phosphorylation was evaluated using
      Western blot. RESULTS Inhibition of EGFR decreased LPS-induced HSC proliferation
      and inflammatory cytokines. The TLR4 antagonist TAK-242, and the c-Src inhibitor,
      PP2 reduced EGFR activation of HSCs, indicating a possible role for the TLR4/c
      Src signaling cascade in LPS-induced HSC activation. CONCLUSIONS Activation of
      HSCs by LPS in vitro, including the expression of inflammatory cytokines and
      mediators of fibrogenesis, were shown to be dependent on the expression of EGFR.

PMID- 30091425
TI  - Corrigendum: Expanded CURB-65: a new score system predicts severity of community
      acquired pneumonia with superior efficiency.
AB  - This corrects the article DOI: 10.1038/srep22911.

PMID- 30091426
TI  - Stimulation of CCK and GLP-1 secretion and expression in STC-1 cells by human
      jejunal contents and in vitro gastrointestinal digests from casein and whey
      proteins.
AB  - The present study evaluates casein and whey protein gastrointestinal digests as
      inducers of CCK and GLP-1 secretion and expression in STC-1 cells. In vitro
      digests were characterized regarding protein, peptide and free amino acid
      content. Digests from the intestinal phase containing small size peptides and
      free amino acids behaved as more potent CCK inducers than digests from the
      gastric phase. However, GLP-1 release was maximized with casein gastric digests
      and whey protein intestinal digests. Human jejunal digests from the same
      substrates showed a comparable response, except for casein jejunal digests which
      exerted a higher effect than in vitro casein gastrointestinal digests. The gene
      expression experiments also showed increased CCK and GLP-1 mRNA levels but the
      differences between the gastric and gastrointestinal phases were not as
      pronounced as observed by quantifying the secreted hormone. Our results
      demonstrate that the degree of protein hydrolysis during digestion plays an
      important role in CCK and GLP-1 secretion.

PMID- 30091427
TI  - Stepwise triple-click functionalization of synthetic peptides.
AB  - The increasing popularity of peptides as promising molecular scaffolds for
      biomedical applications and as valuable biochemical probes makes new methods
      allowing for their modification highly desirable. We describe herein an optimized
      protocol based on a sequence of CuAAC click reactions and selective deprotection
      steps, which leads to an efficient multi-functionalization of synthetic peptides.
      The methodology has been successfully applied to the construction of defined
      heteroglycopeptides and fluorophore-quencher-containing probes for proteases. The
      developed chemistry thus represents an important addition to the available
      toolbox of methods enabling efficient postsynthetic modification of peptides. The
      commercial availability of numerous azide probes further greatly extends the
      application potential of the described methodology.

PMID- 30091428
TI  - Probing the speciation of quaternary ammonium polybromides by voltammetric
      tribromide titration.
AB  - The speciation of quaternary ammonium polybromides (QBr2n+1) was quantitatively
      determined by voltammetric tribromide titration on a Pt ultramicroelectrode
      (UME). The concentration of Br3- in a QBr2n+1-water mixed solution (QBr2n+1-WMS)
      was electrochemically estimated by measuring the steady state current associated
      with the electro-reduction of Br3- in a linear sweep voltammogram (LSV). The pBr3
      titration curves of QBr2n+1-WMSs show 2-4 plateaus, each of which relates to the
      formation of QBr2n+1 from Br3- and Br2. The values of pBr3- at these plateaus can
      be regarded as corrected equilibrium constants of QBr2n+1, K'eq(n), which is
      Keq(n)/gamma+/-, where gamma+/- is a mean activity coefficient in QBr2n+1-WMS.
      Based on the estimated K'eq(n), fractional diagrams of QBr2n+1 were obtained,
      which gave information on QBr2n+1 speciation.

PMID- 30091429
TI  - Local structural changes in graphene oxide layers induced by silver
      nanoparticles.
AB  - Structural changes of graphene oxide (GO) in silver/graphene oxide (AGO)
      nanocomposites are investigated using tip-enhanced Raman scattering (TERS).
      Because of markedly high spatial resolution of the TERS technique, the
      measurements of molecular information at specific nano-scaled positions can be
      achieved by constructing line-profile TERS spectra straight from the center of
      silver nanoparticles (AgNPs) on GO layers. The results show evidences that AgNPs
      cause shortening of C-C bonds beneath AgNPs, flattening of GO layers, and
      critical bending on GO layers. Additionally, a connection of carbon atoms via a C
      C network subsequently expands structural changes with a distance of 200-250 nm
      from the center of AgNPs, even though this distance is larger than the size of
      AgNPs. The proposed model of GO structural changes unveils new understanding
      about changes in properties from GO to AGO nanocomposites, which will contribute
      to a development of advanced nanostructures/nanocomposites in the near future.

PMID- 30091430
TI  - Estimation of G-quartet-forming guanines in parallel-type G-quadruplexes by
      optical spectroscopy measurements of their single-nucleobase substitution
      sequences.
AB  - Since much attention has been paid to in vivo biological functions of G
      quadruplexes, structural analyses of G-quadruplexes are essential for
      understanding their functional mechanisms. Here, we established a simple optical
      spectroscopy-based method for the estimation of G-quartet-forming guanines in
      parallel-type G-quadruplexes using measurements of circular dichroism and the
      thermal melting temperature.

PMID- 30091431
TI  - Sulforaphane ameliorates glucose intolerance in obese mice via the upregulation
      of the insulin signaling pathway.
AB  - Sulforaphane (SFN) is a dietary component with multiple bioactivities; however,
      its role in obesity-related metabolic derangement remains unclear. Here, the
      effect of SFN on the glucose intolerance of obese mice and the underlying
      mechanism were determined. C57B/6J male mice were randomly divided into two
      groups, having free access to water and a normal-fat diet (ND, n = 6) or a high
      fat diet (HFD, n = 33) for 8 weeks; thereafter twelve mice having the greatest
      weight gain among the HFD-fed mice were considered as obese mice. These obese
      mice were randomly divided into two groups and treated orally for 6 weeks with or
      without SFN (100 MUmol per kg bw, 3 times per week). During this period the
      animals were continuously maintained on a ND or a HFD. Blood glucose and serum
      insulin were examined; then glucose tolerance and insulin resistance were
      evaluated. In addition, the expression of insulin signaling pathway-related genes
      in the muscle was determined. Our data showed that the obese mice presented a
      marked insulin resistance and glucose intolerance as compared to the control
      group, while SFN treatment exerted a prominently protective effect. In addition,
      the SFN-treated obese mice had a significantly increased insulin receptor
      substrate 1 (IRS-1) protein level (P < 0.05), markedly elevated Akt activation,
      as well as dramatically enhanced phosphorylation of PDK-1 (P < 0.05) when
      compared with the SFN-untreated obese mice. Moreover, the SFN-treated obese mice
      exhibited a significantly enhanced translocation of GLUT4 (P < 0.05) to the
      plasma membrane in the muscle compared to the obese mice without SFN treatment.
      In conclusion, our results support the notion that SFN acts as a promising agent
      to improve glucose tolerance through the up-regulation of insulin signaling
      mainly involving the IRS-1/Akt/GLUT4 pathway in the muscle.

PMID- 30091432
TI  - Control of catalytic nanoparticle synthesis: general discussion.

PMID- 30091433
TI  - Dioxane-involving reaction for the synthesis of 3-aryl-1-(2
      (vinyloxy)ethoxy)isoquinolines catalyzed by AgOTf.
AB  - Dioxane was found to be involved in the reaction of 2-(arylethynyl)benzaldehydes
      and 3-aminopyrazine-2-carbohydrazide, and underwent a ring-opening reaction
      catalyzed by AgOTf. This domino type procedure provided an efficient method for
      the synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines in good yields via
      the loss of a molecule of 3-aminopyrazine-2-carboxamide.

PMID- 30091434
TI  - Molecular profiling of single axons and dendrites in living neurons using
      electrosyringe-assisted electrospray mass spectrometry.
AB  - The molecular profiling of single axons and dendrites in living neurons could
      provide important information for the better understanding of neuron function.
      Here, electrosyringe-assisted electrospray mass spectrometry (MS) is established
      for the first time to achieve intracellular sampling from one axon or dendrite in
      living neurons for mass spectrometric analysis. The key is the insertion of a
      ~130 nm capillary tip into one axon or dendrite to load the cytosol through
      electro-osmotic flow. The ionization efficiency from the nano-capillary is
      enhanced to guarantee mass spectrometric analysis of multiple components from the
      axon and dendrite. Higher levels of pyroglutamic acid and glutamic acid are
      revealed in the axon compared to in the body and dendrite. This uneven
      distribution is in accordance with the accumulation of neurotransmitters in the
      axon for information delivery. The achievement of electrosyringe-assisted
      electrospray MS is to unveil the molecular distribution in the whole living
      neuron, which offers the feasibility to deeply investigate molecular
      communication between the axon/dendrite and the body inside neurons.

PMID- 30091435
TI  - Chemistry of the fumiquinazolines and structurally related alkaloids.
AB  - Covering: this review covers the literature from 1992 to 2018To date,
      approximately 80 naturally-occurring secondary metabolites which are structurally
      related to fumiquinazolines have been isolated, mainly from marine sources. These
      alkaloids can be classified into twelve different groups and exhibit different
      structure motifs depending on the amino acids from which they are derived. This
      review is focused on isolation, structure elucidation, biological activities,
      biosynthetic pathways, and synthetic studies of these natural products.

PMID- 30091436
TI  - The immunomodulatory role of sulfated chitosan in BMP-2-mediated bone
      regeneration.
AB  - The immunomodulatory property of biomaterials is vital in determining the in vivo
      fate of implants and tissue regeneration. Bone morphogenetic protein-2 (BMP-2)
      has been identified as an effective inducer of osteogenic differentiation for
      bone repair. But it is still unclear how the immunomodulatory effects of
      materials impact on BMP-2-mediated osteogenesis. Herein, this study aims to
      investigate the immunoregulatory role of 2-N,6-O-sulfated chitosan (26SCS), a
      sulfated polysaccharide, in the osteogenetic capacity of BMP-2 and the subsequent
      effects on bone regeneration. It was noted that 26SCS can robustly activate a
      moderate pro-inflammatory macrophage response initially, followed by
      transitioning towards an anti-inflammatory response later on. The immune
      microenvironment caused by 26SCS could facilitate bone marrow stromal cell (BMSC)
      chemoattraction. Furthermore, 26SCS significantly up-regulated the expression of
      BMPR-IA as well as amplified BMP-2-activated BMP/Smad signaling. In addition, the
      26SCS-triggered immune microenvironment had a positive effect on proangiogenesis
      by BMSCs. Our findings suggest that 26SCS may be involved in the induction of a
      favorable immune microenvironment enhancing crosstalk between immune cells and
      stem cells undergoing osteogenic differentiation. This relationship is likely
      responsible for the enhanced bone tissue development observed with 26SCS in an
      ectopic ossification model.

PMID- 30091437
TI  - Synthesis and characterization of rhodium, iridium, and palladium complexes of a
      diarylamido-based PNSb pincer ligand.
AB  - A new diarylmido-based pincer proto ligand (iPrPNHSbPh) with one -PPri2 and one 
      SbPh2 side donor has been synthesized. Three complexes of its amido form were
      prepared using standard metalation techniques: (iPrPNSbPh)PdCl, (iPrPNSbPh)RhCO,
      and (iPrPNSbPh)Ir(COE), where COE = cis-cyclooctene. These complexes were
      compared with their previously reported analogs incorporating a -PPh2 side donor
      in place of -SbPh2. The -SbPh2 donor arm is less donating towards the metal and
      is less strongly trans-influencing, based on the structural and IR spectroscopic
      analysis of the Rh complexes. The redox potential of the Pd complexes is only
      marginally affected by the change from -PPh2 to -SbPh2. (iPrPNSbPh)Ir(COE) proved
      to be a slower and less selective catalyst in the dehydrogenative borylation of
      terminal alkynes (DHBTA) than its -PPh2 analog.

PMID- 30091438
TI  - Controlled synthesis of Co3O4@NiMoO4 core-shell nanorod arrays for efficient
      water splitting.
AB  - Exploitation of environmentally friendly electrocatalysts for a robust oxygen
      evolution reaction (OER) in an alkaline medium is very satisfactory. Here, a very
      low cell voltage of 1.65 V is acquired when Co3O4@NiMoO4/NF is firstly used as a
      bifunctional water splitting catalyst with 10 mA cm-2 in 1.0 M KOH.

PMID- 30091439
TI  - Substrate involvement in dioxygen bond dissociation catalysed by iron
      phthalocyanine supported on Ag(100).
AB  - Dioxygen adsorbs in the end-on configuration on-top of the Fe atoms of an iron
      phthalocyanine monolayer supported on Ag(100) and is partly cleaved at room
      temperature to produce O/FePc/Ag(100). Scanning tunnelling microscopy coupled to
      density functional theory calculations gives the first experimental evidence of
      the substrate involvement in the O2 bond dissociation.

PMID- 30091440
TI  - Tandem Diels-Alder/oxidation-aromatization reactions involving 2-styrylchromones
      and arynes.
AB  - Transition-metal-free Diels-Alder and tandem Diels-Alder/oxidation-aromatization
      reactions of 2-styrylchromones with arynes have been demonstrated under mild
      reaction conditions with a wide range of substrates. The tandem process afforded
      functionalized benzo[c]xanthone derivatives in moderate to good yields. This
      efficient protocol allows rapid access to either dihydrobenzo[c]xanthone and
      benzo[c]xanthone derivatives selectively by simply changing the atmosphere of the
      reaction.

PMID- 30091441
TI  - Anomalous isoelectronic chalcogen rejection in 2D anisotropic vdW TiS3(1-x)Se3x
      trichalcogenides.
AB  - Alloying in semiconductors has enabled many civilian technologies in electronics,
      optoelectronics, photonics, and others. While the alloying phenomenon is well
      established in traditional bulk semiconductors owing to a vast array of available
      ternary phase diagrams, alloying in 2D materials still remains at its seminal
      stages. This is especially true for transition metal trichalcogenides (TMTCs)
      such as TiS3 which has been recently predicted to be a direct gap, high carrier
      mobility, pseudo-1D semiconductor. In this work, we report on an unusual alloying
      rejection behavior in TiS3(1-x)Se3x vdW crystals. TEM, SEM, EDS, and angle
      resolved Raman measurements show that only a miniscule amount (8%) of selenium
      can be successfully alloyed into a TiS3 host matrix despite vastly different
      precursor amounts as well as growth temperatures. This unusual behavior contrasts
      with other vdW systems such as TiS2(1-x)Se2x, MoS2(1-x)Se2x, Mo1-xWxS2, WS2(1
      x)Se2x, where continuous alloying can be attained. Angle-resolved Raman and
      kelvin probe force microscopy measurements offer insights into how selenium
      alloying influences in-plane structural anisotropy as well as electron affinity
      values of exfoliated sheets. Our cluster expansion theory calculations show that
      only the alloys with a small amount of Se can be attained due to energetic
      instability above/below a certain selenium concentration threshold in the ternary
      phase diagrams. The overall findings highlight potential challenges in achieving
      stable Ti based TMTCs alloys.

PMID- 30091442
TI  - Nature-inspired entwined coiled carbon mechanical metamaterials: molecular
      dynamics simulations.
AB  - Entwining-induced robust natural biosystems show superior mechanical performances
      over their counterparts. However, the role played by topological entwinement in
      the mechanical properties of artificial nanohelixes remains unknown. Here, the
      tensile characteristics of nano-entwined carbon nanocoil (ECNC) metamaterials are
      explored by atomistic simulations. The simulation results show that ECNCs exhibit
      heterogeneous pre-stress distribution along the spiral surfaces. The predicted
      stretching stress-strain responses correlate with the topological nano-entwining
      and dimensionality. Topological analysis reveals that the collective stretching
      of the bond and bond angle on the inner hexagon edge of the coils characterizes
      both early and final elastic extensions, whereas the intermediate elasticity is
      exclusively attributed to the inner-edged hexagon-angular deformation. The ECNCs
      impart pronounced tensile stiffnesses to the native structures, surprisingly with
      a maximum of over 13-fold higher stiffness for one triple-helix, beyond the
      scalability of mechanical springs in parallel, originating from the nano
      entwining mechanism and increase in bulkiness. However, the reinforcement in
      strengths is restricted by the elastic strain limits that are degraded in ECNCs
      owing to the steric hindrance effect. All metastructures show superelongation-at
      break due to a successive break-vs.-arrest process. Upon plastic deformation, the
      localized reduction in the radii of ECNCs leads to the formation of carbyne-based
      networks.

PMID- 30091443
TI  - Enhanced recovery after surgery (ERAS) versus conventional postoperative care in
      patients undergoing abdominal hysterectomies.
AB  - OBJECTIVES: In the present study, we aimed to compare the postoperative
      compliance and complications between ERAS and conventional postoperative care in
      patients undergoing abdominal hysterectomies. MATERIAL AND METHODS: This is the
      prospective, randomized, controlled trial, which involved 62 patients, who
      underwent abdominal hysterectomy between December 2016 to February 2017. A total
      of 30 patients formed the ERAS group. A total of 32 patients who received
      conventional perioperative care and matched for age, body mass index (BMI) and
      American Society of Anesthesiologists score were assigned as a control group.
      Groups were compared in terms of patient characteristics [age, body mass index,
      ASA Score, parity, diagnosis, type of surgery, and perioperative intravenous
      fluids], postoperative compliance (postoperative intravenous fluids, time to
      first flatus, first defecation, ambulation, eating solid food, and postoperative
      hospital stay), and postoperative complications. RESULTS: Peri- and post
      operative administrated intravenous fluids were significantly lower in the ERAS
      group (p < 0.001 for both). Time to first flatus (p = 0.001), time to first
      defecation (p < 0.001), and time to eating solid food (p < 0.001) were all
      significantly shorter in the ERAS group. Post-operative early mobilization on the
      first postoperative day was achieved in eight (26.7%) patients in the ERAS group.
      There were no significant differences in complications. One (3.3%) patient in the
      ERAS Group and 11 (34.4%) patients in the Conventional Group required hospital
      readmission after discharge (p = 0.002). CONCLUSION: The ERAS protocol seems to
      be a simple tool for reducing the incidence of postoperative complications and
      shortening hospitalization.

PMID- 30091444
TI  - Brenner tumor of the ovary - ultrasound features and clinical management of a
      rare ovarian tumor mimicking ovarian cancer.
AB  - OBJECTIVES: To describe the ultrasound features of benign Brenner tumor in the
      background of complex clinical and histopathological pictures. MATERIAL AND
      METHODS: We retrospectively identified patients with histologically confirmed
      benign Brenner tumor of the ovary who were treated in our institution in 2003
      2016, and for whom complete imaging, clinical, perioperative and
      histopathological data were available in the database. Ultrasound findings were
      drawn from images and reports using terms and definitions of the International
      Ovarian Tumor Analysis group and pattern recognition description was applied.
      RESULTS: Twenty-three patients were identified, most postmenopausal and
      asymptomatic. On ultrasound, 19/23 tumors were found unilaterally, 4/23
      bilaterally, and 82% of tumors were detected in the left ovary. Most Brenner
      tumors (16/23) contained solid components and revealed no or minimal blood flow
      by subjective color score upon Doppler examination (19/23, 83%). Calcifications
      with shadowing were observed in 57% of all Brenner tumors and in 81% of tumors
      containing solid components. The complex appearance of the tumor misled the
      sonographers to describe the mass as malignant in 9 cases (39%), and frozen
      section was performed perioperatively. Surgery was performed via laparoscopy in
      11 (48%) and via laparotomy in 12 (52%) cases. CONCLUSIONS: The complexity of the
      ultrasound picture, consisting of features like calcifications with acoustic
      shadowing, a poorly vascularized solid mass, and a left-sided localization could
      be signs of a benign Brenner tumor and could preop-eratively help to
      differentiate between benign and malignant tumor.

PMID- 30091445
TI  - Insulin resistance indexes in women with premature ovarian insufficiency - a
      pilot study.
AB  - OBJECTIVES: Premature ovarian insufficiency (POI) is associated with
      hypoestrogenism and an increased risk of metabolic disorders. In many clinics, a
      variety of insulin resistance (IR) tests are used during routine clinical
      assessments. To date, there is no clear opinion about which of these tests should
      be applied in women with premature ovarian insufficiency (POI). Therefore, our
      preliminarily aim was to compare the most frequently used insulin resistance
      indexes in the clinical assessment of a group of POI women and a control group.
      MATERIAL AND METHODS: Our retrospective study included 98 women with
      karyotypically normal spontaneous POI aged 18-39 years and a control group of 78
      healthy women. Each patient was given an oral glucose tolerance test (OGTT) to
      evaluate their insulin release and insulin resistance. In addition, each woman's
      insulin resistance (IR) was evaluated us-ing the homeostasis model assessment for
      insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index
      (QUICKI), the fasting glucose-to-insulin ratio (FGIR), and Matsuda and McAuley
      indexes. The two groups' glucose levels were compared at 0, 60 and 120 min of the
      OGTT. RESULTS: At 0 and 60 min of the OGTT, the insulin levels of the POI women
      were significantly higher than those of the control group. The number of women in
      whom IR was detected using the various kits was comparable between the two
      groups. CONLUSIONS: In conclusion, only the OGTT evaluation revealed a
      significant difference in insulin concentrations between the two study groups.
      The indexes most commonly used to detect IR did not detect differences in IR
      between the POI women and the members of the healthy control group. QUICKI
      detected significantly more women with IR within both study groups than other
      tests did.

PMID- 30091446
TI  - Maternal hypoglycaemia on the 50 g oral glucose challenge test - evaluation of
      obstetric and neonatal outcomes.
AB  - OBJECTIVES: To discuss obstetric and neonatal outcomes of maternal hypoglycaemia
      observed after the 50 g oral glucose challenge test. MATERIAL AND METHODS: A
      retrospective evaluation was made of the results of patients at 24-28 weeks
      gestation of a live singleton pregnancy who underwent a 50 g OGCT at the Health
      Sciences University Gazi Yasargil Training and Research Hos-pital, between
      September 2016 and August 2017. In the 50 g OGCT, 1-hour blood glucose results
      were divided into Low OGCT (< 90 mg/dL) and Normal OGCT (90-139 mg/dL). The
      groups were compared in respect of obstetrics and neonatal outcomes. RESULTS: Of
      2623 pregnant patients applied with the 50 g OGCT, blood glucose was < 140 mg/dL
      in 77.16% (n = 2024), with 11.9% (n = 312) in the Low OGCT group, and the
      remaining 65.26% (n = 1712) in the Normal OGCT group. Based on the comparison of
      the groups, the SGA rate was 7% in the Low OGCT group and 4% in the Normal OGCT
      group; the 5th minute APGAR score was < 7 in 2% of the Low OGCT group and in 1%
      of the Normal OGCT group, while caesarean section rates were 25% and 32%
      respectively (p < 0.05). CONCLUSIONS: The results of the study showed a
      significant association between maternal hypoglycaemia and increased SGA rate,
      decreased 5-minute APGAR scores and reduced caesarean section rates, and this
      relationship should be confirmed with further comprehensive studies.

PMID- 30091447
TI  - The value of serum uric acid in predicting adverse pregnancy outcomes of women
      with hypertensive disorders of pregnancy.
AB  - OBJECTIVES: This study aims to investigate the clinical value of uric acid in
      predicting adverse pregnancy outcomes (APOs) of women with hypertensive disorders
      of pregnancy. MATERIAL AND METHODS: A total of 180 pregnant women with HDP from
      September 2015 to January 2017 were selected for this study. These subjects were
      classified into two groups, according to serum uric acid level: high UA group (n
      = 137) and normal UA group (n = 43). In addition, 180 healthy pregnant women were
      selected and assigned as the control group (n = 180). The monitored biochemical
      indices and APOs in these three groups were analyzed. Furthermore, non
      conditional logistic regression analysis was performed to determine influencing
      factors of APOs in women with HDP and hyperuricemia. RESULTS: The non-conditional
      multi-factor logistic regression analysis revealed that HUA (SUA > 357 umol/L) is
      the risk factor of APOs in women with HDP (OR = 1.258, P < 0.05). CONCLUSIONS:
      Women with HDP and HUA are often accompanied with a variety of abnormal
      biochemical indicators, and is correlated with the severity of the disease and
      APOs.

PMID- 30091448
TI  - Gestational diabetes mellitus (GDM) - do the number of fulfilled diagnostic
      criteria predict the perinatal outcome?
AB  - OBJECTIVES: The aim of the study was to check whether the number of fulfilled
      diagnostic criteria of gestational diabetes mellitus (GDM) had any association
      with patients' characteristics and pregnancy outcomes. MATERIAL AND METHODS: A
      total of 756 women with single pregnancies and GDM who gave birth at the 2nd
      Department of Obstetrics and Gynecology of the Medical University of Warsaw
      between 01.2013-12.2016 were included in a retrospective analysis. Patients were
      divided into 2 groups: A - 499 patients diagnosed with GDM on the basis of one
      diagnostic criterion, B - 257 patients diagnosed with GDM on the basis of more
      than one diagnostic criterion. RESULTS: Patients from group A had lower pre
      pregnancy BMI than those from group B (median 24.9 kg/m2 vs. 26.5 kg/m2,
      p=0.0003). Women from group A were less frequently treated with insulin than
      women from group B (19.1% vs. 32.7%; p=0.00002). Group A had lower median OGTT
      levels than group B (85.9 mg/dL vs. 94.1 mg/dL, p=0,0001; 160.2 mg/dL vs. 197.6
      mg/dL, p=0.0001; 144.8 mg/dL vs. 167.0 mg/dL,p=0.0001; respectively). Moreover,
      in group B the average week of labor was earlier than in group A (mean 38,1 and
      38,5 weeks of gestation, p=0,0006). CONCLUSIONS: Patients who fulfilled more than
      one diagnostic criterion for GDM may have worse pregnancy outcome. We think that
      a number of fulfilled diagnostic criteria for GDM may be an important risk factor
      for insulin therapy during pregnancy and earlier gestational age at delivery.

PMID- 30091449
TI  - Preventing congenital toxoplasmosis - implementation of clinical practice
      guidelines.
AB  - OBJECTIVES: The aim of the study was to evaluate obstetric care of pregnant women
      with regard to prevention of congenital toxoplasmosis. Additionally, we attempted
      to determine the frequency of markers for past infection with Toxoplasma gondii
      in order to characterize the current significance of preventive measures in the
      Polish population. MATERIAL AND METHODS: The analysis of the medical records -
      pregnancy charts of women who presented for delivery - was performed. Patient
      age, place of residence, and toxoplasmosis test (or lack of it) were evaluated.
      Also, further diagnostic management, depending on the serologic result, was
      investigated. RESULTS: Out of 670 pregnant women, 628 (93.73%) underwent at least
      one toxoplasmosis diagnostic test. Out of those, 502 (73%) had a negative result
      (IgG -, IgM -), and 2 (0.32%) had a positive result (IgG +, IgM +), while history
      of infection with Toxoplasma gondii was confirmed (IgG +, IgM -) in 124 (19.75%)
      cases. Repeat testing was required in 183 (29.14%) out of the 628 women.
      CONCLUSIONS: A high rate of women in whom IgG antibodies were not detected in the
      first test and a low rate of women who required repeat testing later in pregnancy
      are noteworthy. Regardless of the healthcare policy, parents should receive
      reliable information about the nature of the disease and possibilities of
      prevention, while medical professionals ought to have easy access to research
      data about the epidemiologic status and recommendations.

PMID- 30091450
TI  - The role of ABC transporters' gene polymorphism in the etiology of intrahepatic
      cholestasis of pregnancy.
AB  - OBJECTIVES: The etiology of intrahepatic cholestasis of pregnancy (ICP) involves
      environmental, hormonal and genetic factors. It is thought that ICP may be
      related to the polymorphic variants of several genes involved in the metabolism
      and transport of bile acids (BA). The goal of our study was to evaluate the
      possible role of genetic polymorphic variants of ABC transporters in patients
      with ICP. MATERIAL AND METHODS: 96 women with ICP (mean age of 30.42 years, mean
      gestational age of 36.83 gestation weeks) and 211 healthy pregnant women (mean
      age of 30.68 years, mean gestational age of 39.05 gestation weeks) were enrolled
      in the study. Genetic analysis was performed using a polymerase chain reaction /
      restriction fragment length polymorphism (PCR/RFLP) method. The following
      polymorphisms were analysed: 1331T > C (V444A) ABCB11 and 1954A > G (R652G)
      ABCB4. RESULTS: Our analysis of frequency of genotypes and alleles of the 1954A >
      G ABCB4 polymorphism revealed no significant differences between the ICP and
      control groups. For the 1331T > C polymorphism of the ABCB11 gene the results
      revealed a higher frequency of 1331CC genotypes in the ICP group (39.58% vs.
      29.38%. OR = 1.57, p = 0.05). Also, the frequency of the 1331C allele was higher
      in the ICP group compared to the control group (64.06% vs. 55.69%, OR = 1.42, p =
      0.03). CONCLUSIONS: The overrepresentation of mutated variants of the 1331T > C
      ABCB11 polymorphism in the ICP group suggests its contribution to the etiology of
      the intrahepatic cholestasis of pregnancy. Analysis of genotypes' co-existence
      pointed to the possibility of the mutated variants of polymorphism 1954A > G
      ABCB4 and 1331T > C ABCB11 having a summation effect on the development of ICP.

PMID- 30091451
TI  - Complications in modern hysteroscopic myomectomy.
AB  - Uterine fibroids (UFs) are common benign tumors of the female genital tract,
      diagnosed in almost one-quarter of women of reproductive age. UFs may cause
      numerous clinical symptoms, including prolonged or heavy menstrual bleeding,
      pelvic pressure symptoms, pain, infertility and others. Submucous fibroids arise
      from the muscular part of the uterus and pen-etrate into the uterine cavity. They
      are mostly managed with the use of hysteroscopic myomectomy (HM), which provides
      direct visualization from the transcervical approach. The sheer number of HM
      standards and techniques is reason enough to review the available literature
      about HM-related complications. HM is a safe and effective treatment in patients
      with the normal size of the uterus and with no more than a few UFs. The procedure
      should not be initiated without adequate preparation and diagnosis, using the
      best methods available.

PMID- 30091452
TI  - Expectant management in postlaparoscopic distal emphysema.

PMID- 30091453
TI  - Jack Aviv: Scientist, instrument wizard, humanist and philanthropist.

PMID- 30091454
TI  - Single question burden of disease assessment in patients referred for patch
      testing.

PMID- 30091455
TI  - The Role of Fault-Zone Architectural Elements on Pore Pressure Propagation and
      Induced Seismicity.
AB  - We used hydrogeologic models to assess how fault-zone properties promote or
      inhibit the downward propagation of fluid overpressures from a basal reservoir
      injection well (150 m from fault zone, Q = 5000 m3 /day) into the underlying
      crystalline basement rocks. We varied the permeability of the fault-zone
      architectural components and a crystalline basement weathered layer as part of a
      numerical sensitivity study. Realistic conduit-barrier style fault zones
      effectively transmit elevated pore pressures associated with 4 years of
      continuous injection to depths of approximately 2.5 km within the crystalline
      basement while compartmentalizing fluid flow within the injection reservoir. The
      presence of a laterally continuous, relatively low-permeability altered/weathered
      basement horizon (kaltered layer = 0.1 * kbasement ) can limit the penetration
      depth of the pressure front to approximately 500 m. On the other hand, the
      presence of a discontinuous altered/weathered horizon that partially confines the
      injection reservoir without blocking the fault fluid conduit promotes downward
      propagation of pressures. Permeability enhancement via hydromechanical failure
      was found to increase the depth of early-time pressure front migration by a
      factor of 1.3 to 1.85. Dynamic permeability models may help explain seismicity at
      depths of greater than 10 km such as is observed within the Permian Basin, NM.

PMID- 30091456
TI  - Euromelanoma in Portugal. How useful was the Euromelanoma campaign between 2010
      and 2017?

PMID- 30091457
TI  - Atezolizumab-associated vitiligo-like leukoderma in a patient with transitional
      cell carcinoma.

PMID- 30091458
TI  - Sodium valproate versus phenytoin monotherapy for epilepsy: an individual
      participant data review.
AB  - BACKGROUND: Epilepsy is a common neurological condition in which abnormal
      electrical discharges from the brain cause recurrent unprovoked seizures. It is
      believed that with effective drug treatment up to 70% of individuals with active
      epilepsy have the potential to become seizure-free, and to go into long-term
      remission shortly after starting drug therapy with a single antiepileptic drug in
      monotherapy.Worldwide, sodium valproate and phenytoin are commonly used
      antiepileptic drugs for monotherapy treatment. It is generally believed that
      phenytoin is more effective for focal onset seizures, and that sodium pvalproate
      is more effective for generalised onset tonic-clonic seizures (with or without
      other generalised seizure types). This review is one in a series of Cochrane
      Reviews investigating pair-wise monotherapy comparisons. This is the latest
      updated version of the review first published in 2001, and updated in 2013 and
      2016. OBJECTIVES: To review the time to treatment failure, remission and first
      seizure of sodium valproate compared to phenytoin when used as monotherapy in
      people with focal onset seizures or generalised tonic-clonic seizures (with or
      without other generalised seizure types). SEARCH METHODS: We searched the
      Cochrane Epilepsy Group's Specialised Register, the Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, ClinicalTrials.gov and the World Health
      Organization (WHO) International Clinical Trials Registry Platform ICTRP on 19
      February 2018. We handsearched relevant journals, contacted pharmaceutical
      companies, original trial investigators and experts in the field. SELECTION
      CRITERIA: Randomised controlled trials (RCTs) comparing monotherapy with either
      sodium valproate or phenytoin in children or adults with focal onset seizures or
      generalised onset tonic-clonic seizures DATA COLLECTION AND ANALYSIS: This was an
      individual participant data (IPD) review. Our primary outcome was time to
      treatment failure and our secondary outcomes were time to first seizure post
      randomisation, time to six-month, and 12-month remission, and incidence of
      adverse events. We used Cox proportional hazards regression models to obtain
      trial-specific estimates of hazard ratios (HRs) with 95% confidence intervals
      (CIs), using the generic inverse variance method to obtain the overall pooled HR
      and 95% CI. MAIN RESULTS: We included 11 trials in this review and IPD were
      available for 669 individuals out of 1119 eligible individuals from five out of
      11 trials, 60% of the potential data. Results apply to focal onset seizures
      (simple, complex and secondary generalised tonic-clonic seizures), and
      generalised tonic-clonic seizures, but not other generalised seizure types
      (absence or myoclonus seizure types). For remission outcomes, a HR of less than 1
      indicates an advantage for phenytoin, and for first seizure and treatment failure
      outcomes a HR of less than 1 indicates an advantage for sodium valproate.The main
      overall results were: time to treatment failure for any reason related to
      treatment (pooled HR adjusted for seizure type 0.88, 95% CI 0.61 to 1.27; 5
      studies; 528 participants; moderate-quality evidence), time to treatment failure
      due to adverse events (pooled HR adjusted for seizure type 0.77, 95% CI 0.44 to
      1.37; 4 studies; 418 participants; moderate-quality evidence), time to treatment
      failure due to lack of efficacy (pooled HR for all participants 1.16 (95% CI 0.71
      to 1.89; 5 studies; 451 participants; moderate-quality evidence). These results
      suggest that treatment failure for any reason related to treatment and treatment
      failure due to adverse events may occur earlier on phenytoin compared to sodium
      valproate, while treatment failure due to lack of efficacy may occur earlier on
      sodium valproate than phenytoin; however none of these results were statistically
      significant.Results for time to first seizure (pooled HR adjusted for seizure
      type 1.08, 95% CI 0.88 to 1.33; 5 studies; 639 participants; low-quality
      evidence) suggest that first seizure recurrence may occur slightly earlier on
      sodium valproate compared to phenytoin. There were no clear differences between
      drugs in terms of time to 12-month remission (pooled HR adjusted for seizure type
      1.02, 95% CI 0.81 to 1.28; 4 studies; 514 participants; moderate-quality
      evidence) and time to six-month remission (pooled HR adjusted for seizure type
      1.05, 95% CI 0.86 to 1.27; 5 studies; 639 participants; moderate-quality
      evidence).Limited information was available regarding adverse events in the
      trials and we could not make comparisons between the rates of adverse events on
      sodium valproate and phenytoin. Some adverse events reported with both drugs were
      drowsiness, rash, dizziness, nausea and gastrointestinal problems. Weight gain
      was also reported with sodium valproate and gingival hypertrophy/hyperplasia was
      reported on phenytoin.The methodological quality of the included trials was
      generally good, however four out of the five trials providing IPD for analysis
      were of an open-label design, therefore all results were at risk of detection
      bias. There was also evidence that misclassification of seizure type may have
      confounded the results of this review, particularly for the outcome 'time to
      first seizure' and heterogeneity was present in analysis of treatment failure
      outcomes which could not be explained by subgroup analysis by epilepsy type or by
      sensitivity analysis for misclassification of seizure type. Therefore, for
      treatment failure outcomes we judged the quality of the evidence to be moderate
      to low, for 'time to first seizure' we judged the quality of the evidence to be
      low, and for remission outcomes we judged the quality of the evidence to be
      moderate. AUTHORS' CONCLUSIONS: We have not found evidence that a significant
      difference exists between valproate and phenytoin for any of the outcomes
      examined in this review. However detection bias, classification bias and
      heterogeneity may have impacted on the results of this review. We did not find
      any outright evidence to support or refute current treatment policies. We
      recommend that future trials be designed to the highest quality possible with
      consideration of masking, choice of population, classification of seizure type,
      duration of follow-up, choice of outcomes and analysis, and presentation of
      results.

PMID- 30091459
TI  - Nationwide population-based study of trends and regional variation in breast
      conserving treatment for breast cancer.
AB  - BACKGROUND: Landmark trials have shown breast-conserving surgery (BCS) combined
      with radiotherapy to be as safe as mastectomy in breast cancer treatment. This
      population-based study aimed to evaluate trends in BCS from 1989 to 2015 in nine
      geographical regions in the Netherlands. METHODS: All women diagnosed between
      1989 and 2015 with primary T1-2 N0-1 breast cancer, treated with BCS or
      mastectomy, were identified from the Netherlands Cancer Registry. Crude and case
      mix-adjusted rates of BCS were evaluated and compared between nine Dutch regions
      for two time intervals: 1989-2002 and 2003-2015. The annual percentage change in
      BCS per region over time was assessed by means of Joinpoint regression analyses.
      Explanatory variables associated with the choice of initial surgery were
      evaluated using multivariable logistic regression. RESULTS: A total of 202 934
      patients were included, 82 200 treated in 1989-2002 and 120 734 in 2003-2015.
      During 1989-2002, the mean rate of BCS was 50.6 per cent, varying significantly
      from 39.0 to 71.7 per cent between the nine regions. For most regions, a marked
      rise in BCS was observed between 2002 and 2003. During 2003-2015, the mean rate
      of BCS increased to 67.4 per cent, but still varied significantly between regions
      from 58.5 to 75.5 per cent. A significant variation remained after case-mix
      correction. CONCLUSION: This large nationwide study showed that the use of BCS
      increased from 1989 to 2015 in the Netherlands. After adjustment for explanatory
      variables, a large variation still existed between the nine regions. This
      regional variation underlines the need for implementation of a uniform treatment
      and decision-making strategy.

PMID- 30091460
TI  - Unveiling the structure of a novel artificial heme-enzyme with peroxidase-like
      activity: A theoretical investigation.
AB  - Fe(III)-Mimochrome VI (MC6) is a recently reported artificial heme-peptide
      conjugate system with a high peroxidase-like activity. By design, its structure
      features a five-coordinated Fe(III)-deuteroporphyrin active site, embedded in a
      compact alpha-helix-heme-alpha-helix "sandwich" motif. Up to now, no detailed MC6
      structural characterization is available. In this work we propose a theoretical
      investigation based on molecular dynamics (MD) simulations and hybrid quantum
      mechanics/molecular mechanics (QM/MM) optimizations, aimed to shed light on
      several Fe(III)-MC6 structural features and to validate the de novo designed
      fold. Key structural elements were analyzed to achieve indirect insight relevant
      to understand Fe(III)-MC6 catalytic performances in solution. Extensive MD
      simulations showed a partial stability of the "sandwich" fold in water solution.
      The smaller peptide chain bonded to the heme revealed a high conformational
      freedom, which promoted the exposition of the heme distal side to the solvent.
      Regarding the accessibility of water molecules, even in Fe(III)-MC6 "closed"
      structure the heme cavity appeared hydrated, suggesting an easy accessibility by
      exogenous ligands. Fe(III)-MC6 structure in both high and low spin states was
      then further characterized through hybrid QM/MM optimizations. In particular, an
      accurate description of the active site structure was obtained, allowing a direct
      comparison of Fe(III)-MC6 coordination environment with that observed in the
      Horseradish Peroxidase crystal structures. Our results suggest a structural
      similarity between Fe(III)-MC6 and the natural enzyme. This study supports the
      interpretation of data from experimental Fe(III)-MC6 structural and functional
      characterization and the rational design of new artificial mimics with improved
      catalytic performances.

PMID- 30091461
TI  - Quality Changes after Implementation of an Episode of Care Model with Strict
      Criteria for Physical Therapy in Ontario's Long-Term Care Homes.
AB  - OBJECTIVES: To describe the proportion of residents receiving rehabilitation in
      long-term care (LTC) homes, and scores on activities of daily living (ADL) and
      falls quality indicators (QIs) before and after change from fee-for-service to an
      episode of care model; and to evaluate the effect of the change on the QIs. DATA
      SOURCES: Secondary data were collected from all LTC homes in Ontario, Canada,
      between January 1, 2011 and March 31, 2015. Variables of interest were the
      proportion of residents per home receiving physical therapy (PT), and the scores
      on seven ADL and one falls QI. STUDY DESIGN: Retrospective, longitudinal study.
      DATA EXTRACTION: All data were extracted from the Resident Assessment Instrument
      Minimum Data Set. PRINCIPAL FINDINGS: Fewer residents received PT after the
      policy change (84.6 percent, 2011; 56.6 percent, 2015). The policy change was
      associated with improved performance on several ADL QIs. However, having a large
      proportion of residents receive no PT or little PT was associated with poorer
      performance on two of the QIs measuring improvement in ADLs [No PT: -0.029 (
      0.043 to -0.014); -0.048 (-0.068 to -0.027). PT <45 minutes per week: -0.012 (
      0.026 to -0.002); -0.026 (-0.045 to -0.007); p < .01]. CONCLUSIONS: While
      controversial, the policy and subsequent PT service delivery change appears to be
      associated with improved performance on several ADL QIs, except in homes where a
      large proportion of residents receive no PT and low time-intensive PT.

PMID- 30091462
TI  - Functional characterization of recurrent FOXA2 mutations seen in endometrial
      cancers.
AB  - FOXA2, a member of the forkhead family of DNA-binding proteins, is frequently
      mutated in uterine cancers. Most of the mutations observed in uterine cancers are
      frameshifts and stops. FOXA2 is considered to be a driver gene in uterine
      cancers, functioning as a haploinsufficient tumor suppressor. The functional
      consequences of FOXA2 mutations, however, have not yet been determined. We
      evaluated the effects that frameshift mutations and a recurrent missense mutation
      have on FOXA2 transcriptional activity. Recurrent N-terminal frameshifts resulted
      in truncated proteins that failed to translocate to the nucleus and have no
      transcriptional activity using an E-cadherin/luciferase reporter assay. Protein
      abundance was reduced for the recurrent p.S169 W mutation, as was transcriptional
      activity. A C-terminal frameshift mutation had increased FOXA2 levels evidenced
      by both Western blot and immunofluorescence. Given that FOXA2 is a recognized
      activator of E-cadherin (CDH1) expression and E-cadherin's potential role in
      epithelial-to-mesenchymal transition in a wide range of cancer types, we tested
      the hypothesis that FOXA2 mutations in primary uterine cancer specimens would be
      associated with reduced CDH1 transcript levels. qRT-PCR revealed significantly
      lower levels of CDH1 expression in primary tumors with FOXA2 mutations. Our
      findings in vitro and in vivo suggest that reduced transcriptional activity
      associated with FOXA2 mutations in uterine cancers is likely to contribute to
      protumorigenic changes in gene expression.

PMID- 30091463
TI  - Cost comparison and determinants of out-of-pocket payments on child delivery care
      in Bangladesh.
AB  - OBJECTIVES: The objective of this study is to capture the relevant out-of-pocket
      (OOP) costs, coping mechanisms, and associated factors that are related to child
      delivery in Bangladesh through the use of nationwide household level data. DATA
      AND METHODS: The study was conducted using a secondary data source of the latest
      Bangladesh Demographic and Health Survey 2014. A cross-sectional survey was
      performed for 6 months, from June to November 2014, where closed-ended questions
      regarding child delivery-related expenditure were included. Log linear regression
      and descriptive analysis methods were used to analyze these data. RESULTS:
      Analysis indicated that the average self-reported OOP payment per child delivery
      was US$ 79.23 (SD +/-128.05). The highest OOP was observed for C-section (US$
      249.89, SD +/-153.54), followed by institutional normal delivery (US$ 61.62, SD
      +/-75.28). The average cost per normal home delivery was US$ 15.89 (SD +/-25.84).
      The richest quintile spent significantly more than the poorest quintile regarding
      C-section (US$ 281 vs US$ 204), normal delivery at an institution (US$ 80 vs US$
      65), and even normal delivery at home (US$ 22 vs US$ 13). CONCLUSIONS: The study
      showed that there was a huge variation of OOP, which was dependent on the
      facility and socioeconomic demographic status of the households. As such, policy
      efforts need to focus on lowest wealth quintiles to avoid economic burdens during
      child delivery-related activities, and therefore, financial risk protection
      should be provided. Social health insurance might be an option for financing
      during child delivery, which is in line with the core objective of the Healthcare
      Financing Strategy of Bangladesh, which is to achieve universal health coverage.

PMID- 30091464
TI  - Use of metformin and survival of patients with high-grade glioma.
AB  - High-grade glioma (HGG) is associated with poor prognosis. Drug repurposing
      evolves as new modality to improve standard therapy. The antidiabetic drug
      metformin has been found to inhibit glioma cell growth in vitro and in vivo. The
      aim of the present retrospective cohort study was to evaluate the survival of
      patients with HGG with or without treatment with metformin, based on a large
      cohort of a cancer registry. The analysis included 1,093 patients with HGG
      diagnosed between 1998 and 2013 from the population-based clinical cancer
      registry Regensburg (Germany), which covers 2.1 Mio inhabitants and 98% of all
      cancer diagnoses. We performed multivariable adjusted Cox-regression analyses.
      Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS)
      and progression-free survival (PFS) of patients with HGG with or without
      treatment with metformin were obtained. Use of metformin was associated with a
      significantly better overall and progression-free survival of patients with WHO
      grade III glioma (HR for OS = 0.30; 95% CI = 0.11-0.81, HR for PFS = 0.29; 95% CI
      = 0.11-0.78), while there were no significant relations with OS (HR = 0.83; 95%
      CI = 0.57-1.20) or PFS (HR = 0.85; 95% CI = 0.59-1.22) in patients with WHO grade
      IV glioma. In conclusion, use of metformin is associated with better overall and
      progression-free survival of patients with WHO grade III. Possible underlying
      mechanisms include the higher prevalence of IDH mutations in WHO grade III
      glioma, which might sensitize to the metabolic drug metformin.

PMID- 30091465
TI  - Doctors' career choices in health systems constrained by national medical exams:
      A discrete choice experiment.
AB  - Previous studies that addressed factors influencing junior doctors' career
      decisions have failed to consider that the market for medical specialty is
      regulated and doctors are not always able to pursue their career of choice. There
      is the concern that the National Medical Exam that doctors have to take in many
      countries conditions their career choices and is behind the low efficacy of
      policies for retaining doctors in rural areas. In this paper, we use data from a
      Discrete Choice Experiment applied to a large sample of Portuguese junior doctors
      (N = 503) who had already taken their Medical Exam but had not chosen their
      medical specialty yet. We show that the exam score is de facto a strong predictor
      for (different) job preferences, but only for doctors who are amongst the highest
      and the lowest exam scores. For all others-almost half of our sample-geographical
      attachment (having lived or studied in rural areas or in metropolis) is more
      relevant in determining specialization decisions. Having a good work-life
      balance, specially amongst female physicians, is also an important determinant of
      specialty choice. Using latent-class analysis may help policymakers profiling
      different groups of doctors and tailoring incentive packages according to their
      characteristics.

PMID- 30091466
TI  - Bone-targeted delivery of TGF-beta type 1 receptor inhibitor rescues uncoupled
      bone remodeling in Camurati-Engelmann disease.
AB  - Camurati-Engelmann disease (CED) is a genetic bone-modeling disorder mainly
      caused by mutations in the gene that encodes transforming growth factor-beta1
      (TGF-beta1). Symptoms of CED include bone pain, fractures, and dysplasia.
      Currently, effective therapies for bone fracture and dysplasia in CED are
      urgently needed. We have demonstrated that TGF-beta1 is a coupling factor for
      bone remodeling and is aberrantly activated in CED. Daily injection of TGF-beta
      type 1 receptor inhibitor (TbetaR1I) attenuated CED symptoms, but this systemic
      administration caused serious side effects. In this study, we created a conjugate
      linking TbetaR1I and alendronate, which delivered TbetaR1I specifically to bone.
      After weekly injection of the conjugate for 8 weeks, normal bone morphology and
      remodeling in CED mice was maintained with a minimum effective dose 700 times
      lower than TbetaR1I injection. Additionally, we found that the conjugate restored
      normal bone turnover by reducing the number of osteoblasts and osteoclasts,
      maintained a regular osteogenic microenvironment by regulating the formation of
      CD31 and Endomucin double-positive vessels, and preserved ordinary bone formation
      via inhibition of the migration of leptin-receptor-positive cells. Thus,
      targeting delivery of TbetaR1I to bone is a promising therapy for CED and other
      uncoupled bone remodeling disorders.

PMID- 30091467
TI  - Management of atrial fibrillation in older patients: A network meta-analysis of
      randomized controlled trials.

PMID- 30091468
TI  - Paradoxical preexcitation during cryoablation of a concealed parahisian accessory
      pathway.
AB  - A 16-year-old male presented with an orthodromic atrioventricular reentrant
      tachycardia over a concealed parahisian accessory pathway (AP). Cryoablation of
      the AP resulted in transient manifestation of a fully preexcited sinus rhythm of
      parahisian AP morphology. Potential causes for the paradoxical preexcitation
      include inadvertent atrioventricular nodal block, sourse-sink mismatch, as well
      as the activation of a dormant AP capable of anterograde conduction.

PMID- 30091469
TI  - The toad fly Lucilia bufonivora: its evolutionary status and molecular
      identification.
AB  - The blow fly genus Lucilia is composed largely of saprophages and facultative
      myasis agents, including the economically important species Lucilia cuprina
      (Wiedemann) (Diptera: Calliphoridae) and Lucilia sericata (Meigen). Only one
      species is generally recognized as an obligate agent of myiasis, Lucilia
      bufonivora Moniez, and this is an obligate parasite of toads. Lucilia silvarum
      (Meigen), a sister species, behaves mainly as a carrion breeder; however, it has
      also been reported as a facultative parasite of amphibians. Morphologically,
      these species are almost identical, and historically this has led to
      misidentification, taxonomic ambiguity and a paucity of studies of L. bufonivora.
      In this study, dipterous larvae were analysed from toad myiasis cases from the
      U.K., The Netherlands and Switzerland, together with adult specimens of fly
      species implicated in amphibian parasitism: L. bufonivora, L. silvarum and
      Lucilia elongata Shannon (from North America). Partial sequences of two genes,
      cox1 and ef1alpha, were amplified. Seven additional blow fly species were
      analysed as outgroups. Bayesian inference trees of cox1, ef1alpha and a combined
      gene dataset were constructed. All larvae isolated from toads were identified as
      L. bufonivora and no specimens of L. silvarum were implicated in amphibian
      myiasis. This study confirms L. silvarum and L. bufonivora as distinct sister
      species and provides unambiguous molecular identification of L. bufonivora.

PMID- 30091470
TI  - Cascaded systems analysis of shift-variant image quality in slit-scanning breast
      tomosynthesis.
AB  - PURPOSE: Digital breast tomosynthesis (DBT) is becoming an important part of
      breast cancer screening and diagnosis. Compared to two-dimensional mammography,
      tomosynthesis introduces limited three-dimensional (3D) resolution, but maintains
      high in-plane resolution, low dose, and allows for similar clinical protocols.
      The scanning motion and oblique projections of tomosynthesis acquisitions
      introduce shift-variance to the image quality, in addition to effects such as
      source blurring and geometric magnification. Shift-variant detector response
      caused by oblique incidence has been extensively studied previously and is most
      easily mitigated by letting the source and detector move in sync. In addition,
      conical reconstruction grids, that is, a grid aligned with the central
      tomosynthesis projection, have been proposed to compensate for magnification
      effects. This paper introduces a shift-variant cascaded systems model for
      tomosynthesis and validates it against measurements. As an example, the model was
      used to investigate the shift-variance of a tomosynthesis system. METHODS: The
      shift-variant cascaded systems model was validated on a slit-scanning photon
      counting DBT system, with synchronous source-detector movement, using simple back
      projection in a conical reconstruction volume. The modulation transfer function
      (MTF), normalized noise-power spectrum (NNPS), and detective quantum efficiency
      (DQE) were used as figures of merit. Simulations were performed for single points
      while measurements were done over a finite volume, assuming local shift
      invariance. To investigate the full extent of shift-variance, 80 locations across
      the volume were simulated, and the MTF and DQE at 2.5 lp/mm were calculated as a
      function of position. RESULTS: The simulated metrics generally agreed well with
      their corresponding measurements. The frequency at 50% MTF along the scan
      direction showed a relatively small variation, ranging from 2.1 to 2.4 lp/mm for
      the different locations. The frequency at 50% MTF along the chest-mammilla
      direction showed a larger variation, ranging from 2.9 to 3.8 lp/mm. All points
      exhibited a similarly shaped NNPS but the noise magnitude varied with slice
      height. The zero-frequency DQE in reconstructed slices was lower than that of the
      projections, an effect likely caused by noise-aliasing increasing the zero
      frequency noise. CONCLUSIONS: A shift-variant cascaded systems model has been
      developed for slit-scanning tomosynthesis using simple back-projection. The model
      was successfully validated against measurements. Even though the study was
      performed on a slit-scanning system, several parts of the framework can be
      applied and extended to other tomosynthesis geometries. The conical
      reconstruction grid has low variation in image quality in the scan direction
      where the 3D information is acquired, but source and geometric magnification
      still dominate in the slit direction, causing a larger variation in image
      quality. We conclude that image quality is close to shift-invariant in the scan
      direction, but not in the height and chest-mammilla directions, and we recommend
      that small measurement volumes are used when measuring image quality in these
      directions to minimize the effects of shift variance.

PMID- 30091471
TI  - Do Maternal Dietary Antioxidants Modify the Relationship Between Binge Drinking
      and Small for Gestational Age? Findings from a Longitudinal Cohort Study.
AB  - BACKGROUND: Vitamin C, vitamin E, and carotenoids are potent dietary antioxidants
      that have been shown to attenuate ethanol-induced harm in animal models of fetal
      alcohol spectrum disorders. A diet low in antioxidant-rich foods may induce a
      state of oxidative stress in the context of maternal alcohol consumption during
      pregnancy, potentially causing growth restriction in the developing fetus.
      METHODS: We conducted a secondary analysis of a longitudinal U.K. birth cohort.
      The sample comprised 9,699 women and their babies in Avon, U.K., with an
      estimated delivery date between April 1, 1991 and December 31, 1992. Alcohol
      consumption data were self-reported at 18 weeks' gestation via a postal
      questionnaire. Women reported any binge drinking (>=4 U.K. units/occasion) during
      the past month. Dietary data were self-reported at 32 weeks' gestation using a
      food frequency questionnaire. Estimated intakes of vitamins C and E and
      carotenoids were categorized into quartiles. Logistic regression models with
      interaction terms were used to investigate relationships between maternal binge
      drinking, dietary antioxidants, and fetal growth. Models were adjusted for
      maternal sociodemographic and lifestyle characteristics. Small for gestational
      age (SGA; <10th percentile) was defined using customized birth centiles. RESULTS:
      In the unadjusted models, binge drinking was associated with higher risk of SGA
      birth (odds ratio [OR] 1.38, 95% confidence interval [CI] 1.10, 1.72, p = 0.005),
      and higher maternal intakes of vitamin C (OR = 0.90, 95% CI 0.84, 0.96, p =
      0.002) and vitamin E (OR = 0.90, 95% CI 0.84, 0.95, p < 0.0001) were associated
      with lower risk of SGA birth. However, addition of potentially confounding
      variables attenuated these relationships. Likelihood ratio tests indicated that
      interaction terms were not significant for vitamin C (p = 0.116), vitamin E (p =
      0.059), or carotenoid intakes (p = 0.174). CONCLUSIONS: There was no evidence of
      maternal intake of dietary antioxidants modifying the relationship between
      maternal binge drinking and SGA birth.

PMID- 30091472
TI  - How Acts of Infidelity Promote DNA Break Repair: Collision and Collusion Between
      DNA Repair and Transcription.
AB  - Transcription is a fundamental cellular process and the first step in gene
      regulation. Although RNA polymerase (RNAP) is highly processive, in growing cells
      the progression of transcription can be hindered by obstacles on the DNA
      template, such as damaged DNA. The authors recent findings highlight a trade-off
      between transcription fidelity and DNA break repair. While a lot of work has
      focused on the interaction between transcription and nucleotide excision repair,
      less is known about how transcription influences the repair of DNA breaks. The
      authors suggest that when the cell experiences stress from DNA breaks, the
      control of RNAP processivity affects the balance between preserving transcription
      integrity and DNA repair. Here, how the conflict between transcription and DNA
      double-strand break (DSB) repair threatens the integrity of both RNA and DNA are
      discussed. In reviewing this field, the authors speculate on cellular paradigms
      where this equilibrium is well sustained, and instances where the maintenance of
      transcription fidelity is favored over genome stability.

PMID- 30091473
TI  - Distribution of health facilities in Nigeria: Implications and options for
      Universal Health Coverage.
AB  - BACKGROUND: Nigeria is considering adopting Universal Health Coverage (UHC) as an
      official policy target to ensure access to quality health care services for her
      population without financial hardship. To facilitate discussion on the topic, the
      President of Nigeria convened a UHC summit in March 2014 to discuss Nigeria's
      options and strategies to achieve UHC. A strategy for achieving UHC requires
      analysis of the available infrastructure to deliver the services. We review the
      geographic and sectoral distribution of health facilities in Nigeria and discuss
      implications on the UHC strategy selected. METHODS: Secondary analysis of data
      from the Federal Ministry of Health's facility register was performed to assess
      the geographic and sectoral distribution of health facilities in Nigeria.
      Additionally, an extensive literature review was conducted to understand UHC
      strategies used by various countries and the associated health facility
      requirements. RESULTS: Primary health facilities make up 88% of health facilities
      in Nigeria while secondary and tertiary health facilities make up 12% and 0.25%,
      respectively. There are more government-owned health facilities than privately
      owned health facilities (67% vs 33%). Secondary health facilities are
      predominantly privately owned. The ratio of public to private health facilities
      is much higher in the northern part of the country than in the southern part.
      CONCLUSIONS: The distribution of health facilities across Nigeria is nonuniform.
      As such, a UHC strategy must be responsive to the variation in health facility
      distribution across the country. Additional investments are needed in some parts
      of the country to improve access to tertiary health facilities and leverage
      private sector capacity.

PMID- 30091474
TI  - Influence of exogenously applied nitric oxide on strawberry (Fragaria * ananassa)
      plants grown under iron deficiency and/or saline stress.
AB  - A study was carried out to assess the protective effects of exogenously applied
      nitric oxide (NO) in the form of its donor sodium nitroprusside (SNP) to
      strawberry seedlings (Fragaria * ananassa cv. Camarosa) grown under iron
      deficiency (ID), salinity stress or combination of both. The experimental design
      contained control, 0.1 mM FeSO4 (ID, Fe deficiency); 50 mM NaCl (S, Salinity) and
      ID + S. Plants were sprayed with 0.1 mM SNP or 0.1 mM sodium ferrocyanide, an
      analogue of SNP containing no NO. The deleterious effects of ID + S treatments on
      plant fresh and dry matters, total chlorophyll and chlorophyll fluorescence were
      more striking than those caused by the ID or S treatment alone. Furthermore,
      combination of salinity and iron stress exacerbated electrolyte leakage (EL) and
      the levels of malondialdehyde (MDA) and hydrogen peroxide (H2 O2 ) in plant
      leaves compared to those in plants grown with either of the single stresses. NO
      treatment effectively reduced EL, MDA and H2 O2 in plants grown under stress
      conditions applied singly or in combination. Salt stress alone and with ID
      reduced the superoxide dismutase (EC1.15.1.1) and catalase (EC 1.11.1.6)
      activities but increased that of POD (EC 1.17.1.7). Exogenously applied NO led to
      significant changes in antioxidant enzyme activities in either ID or S than those
      by ID+S. Overall, exogenously applied NO was more effective in mitigating the
      stress-induced adverse effects on the strawberry plants exposed to a single
      stress than those due to the combination of both stresses.

PMID- 30091475
TI  - Metagenome complexity and template length are the main causes of bias in PCR
      based bacteria community analysis.
AB  - Multitemplate PCR is used widely for the study of microbial community diversity.
      Although such studies have established the abundance of different groups within
      many natural ecosystems, these reports are limited by uncertainties such as bias
      and artifacts in the PCR. Bias which is introduced by the simultaneous
      amplification of specific genes from complex mixtures of templates remains poorly
      understood. In this study, factors leading to the bias of the multitemplate PCR
      in bacterial communities were examined and optimized. Comparisons between PCR
      cycle parameters, DNA polymerases, PCR primer degeneracy, and 16S rRNA gene
      fragments GC content, revealed that annealing temperatures and DNA structure are
      predominant factors contributing to the observed bias. Pre-digestion of
      metagenomic DNA with the restriction enzyme Sau3A I and decreased annealing
      temperature reduced the bias significantly. The application of these optimized
      conditions to the ten-species model community in a soil sample verified the
      validity of these treatments.

PMID- 30091476
TI  - Sensors and signals: the role of reactive oxygen species in hypoxic pulmonary
      vasoconstriction.
AB  - When lung cells experience hypoxia, the functional response, termed hypoxic
      pulmonary vasoconstriction, activates a multitude of pathways with the goal of
      optimizing gas exchange. While previously controversial, overwhelming evidence
      now suggests that increased reactive oxygen species - produced at complex III of
      the mitochondrial electron transport chain and released into the intermembrane
      space - is the cellular oxygen signal responsible for triggering hypoxic
      pulmonary vasoconstriction. The increased reactive oxygen species (ROS) activate
      many downstream targets that ultimately lead to increased intracellular ionized
      calcium concentration and contraction of pulmonary arterial smooth muscle cells.
      While the specific targets of ROS signals are not completely understood, it is
      clear that this signalling pathway is critical for development and for normal
      lung function in newborns and adults.

PMID- 30091477
TI  - The roles of, activities of, and competencies for, community nursing services in
      rural Vietnam: Implications for policy decisions.
AB  - Community health workforce plays a vital role in providing primary health care
      services as per the needs of residents; however, few studies have examined how
      nurses work within commune health centers (CHCs). Using qualitative methods
      including interviews and focus group discussions with key stakeholders, this
      study explores the roles, activities, and competencies required of community
      nursing services in rural districts within Vietnam. Two primary roles were
      identified: CHC nursing and family nursing. For the latter, in addition to
      providing people with general health care and health communication, they were
      expected to also deliver psychological care. CHC nursing fulfilled more roles and
      required four specific competencies: clinical care, communication, management,
      and planning/coordination activities. Despite these various roles serving people
      within a community, few ongoing efforts at either the local or national level are
      aimed at supporting these nurses. The study highlights the need for policy
      decisions via either developing a new job position policy or adapting the
      existing policy by integrating new roles into the existing positions of CHC
      nurses in Vietnam.

PMID- 30091478
TI  - Examining the association between educational attainment and life expectancy in
      MENA region: A panel data analysis.
AB  - BACKGROUND: The purpose of this study is to investigate the association between
      educational attainment and life expectancy in 18 countries in MENA region.
      METHODS: We used World Bank database for a panel of 18 MENA countries during the
      years 1995 to 2009. We used Life Expectancy at Birth, as the key health care
      output measure. Additionally, we used six health care input independent
      variables. All variables were transformed into natural logarithms. We estimated
      the production function using Cobb-Douglas function. RESULTS: Results indicate
      that 1% increase in educational attainment of males 25 to 34 years old, males 25
      years and older, females 25 to 34 years old, females 25 years and older, and
      females aged 15 to 44 years old will increase life expectancy by 0.14%, 0.07%,
      0.04%, 0.03%, and 0.04%, respectively, while everything else remains constant.
      CONCLUSION: Our results suggest that for MENA region countries investing in
      education to broaden access would improve health outcomes and life expectancy.
      Boosting educational attainment for both male and female population may close the
      life expectancy gaps between the MENA region and other developed countries, and
      males and females within the same country. Education attainment has the potential
      to be a social remedy for better health outcomes in MENA countries.

PMID- 30091479
TI  - Do HIV prevention interventions in Asia lead to increase in condom utilization?:
      A meta-analysis study.
AB  - This meta-analytic review synthesizes the findings of published independent
      studies that assessed the effectiveness of HIV prevention interventions in
      promoting condom usage in Asia. We focused on 20 studies that used randomized
      control studies to establish whether HIV prevention interventions lead to
      increased condom utilization. As compared with the average control group client,
      we found that 68% of the clients who participated in an intervention group
      increased their condom usage. The effectiveness of HIV prevention intervention is
      not related to country and rural-urban contexts, to male-female samples, to the
      type of outcome measured, or the timing of the latest follow-up assessment. The
      implications of these findings are that policy-makers, health administrators, and
      international donors should view behavioral HIV prevention interventions as an
      effective approach through which to increase condom usage in order to reduce the
      HIV infection rate in Asia.

PMID- 30091480
TI  - Dispersive Forces and Dipole Moment Increase as Driving Forces for the Formation
      of an Unprecedented Metallophilic Heterotrimetallic System.
AB  - The crystal structure of the polymeric complex [Au5 Ag2 Tl3 (C6 F5 )10 (L1 )2 ]n
      (L1 =1-aza-4,10-dithia-7-oxacyclododecane) displays heterotrimetallic
      Ag???Au???Tl moieties and is held by unsupported metallophilic interactions. This
      complex emits at 500 nm in the solid state. Ab initio calculations show that the
      large thermodynamic stability that helps the formation of this heterotrimetallic
      system arises from the combination of dispersive forces and a very large dipole
      moment in the supramolecular arrangement.

PMID- 30091481
TI  - Monitoring mRNA transcription of genes involved in early pregnancy from
      endometrium and peripheral blood mononuclear cells of pregnant pigs with
      different parity.
AB  - The reproductive success of mammals is largely dependent on the interaction
      between maternal and foetal interfaces during early pregnancy. Particularly,
      immune cells which reside at the maternal endometrium can modulate the conception
      and placental vascularization. In this study, we analysed the transcription of
      genes involved in early pregnancy from endometrium and peripheral blood
      mononuclear cells (PBMCs) of pregnant pigs with different parity. Briefly, three
      groups of female pigs were divided based on parity (0, 2 and 5) and each group
      was artificially inseminated. Within 30 days of gestation, the total RNA was
      isolated from the endometrium and PBMCs of sacrificed experimental pigs and the
      expression patterns of genes involved in early pregnancy were monitored by
      quantitative real-time RT-PCR. Results indicated absence of correlation between
      increased parity and the expression of vascular endothelial growth factor (VEGF)
      and hypoxia-inducible factor 1-alpha (HIF-1alpha) mRNA in endometrium among the
      groups of pigs analysed. Yet, the mRNA levels of Fas, Fas ligand (FasL) and
      tumour necrosis factor-alpha (TNF-alpha) in the endometrium of parity 5 sows were
      much higher than those of pregnant gilts (parity 0), and the mRNA ratios of both
      TNF-alpha:interleukin-4 (IL-4) and IFN-gamma (interferon-gamma):interleukin-10
      (IL-10) in PBMCs of pregnant pigs were augmented with increasing parity.
      Furthermore, the mRNA levels of TNF-alpha and IFN-gamma in PBMCs of pregnant pigs
      were inversely correlated with litter size. These combined results may
      demonstrate that increased parity of pregnant pigs leads to enhance Th1-prone
      immunity within the maternal-foetal interface during early pregnancy.

PMID- 30091482
TI  - De Novo Designed alpha-Helical Coiled-Coil Peptides as Scaffolds for Chemical
      Reactions.
AB  - Coiled coils (CCs) are well-understood protein-folding motifs. They appear in a
      variety of oligomer states and as homo- and heteromeric assemblies. This
      versatility and the general accessibility by de novo design makes them ideal
      building blocks for synthetic biology. This Minireview highlights the efforts
      being made in designing small peptide catalysts or reaction templates based on
      the CC scaffold. The first reports described autocatalysis or mediation of
      peptide ligation based on CC recognition. Over the years, the designs became more
      advanced, catalyzing ester hydrolysis, acyl transfer and redox reactions with
      partial enzyme-like reactivity. Due to the ability to control CC assembly, and,
      in heterodimeric systems, the association and dissociation, the CC motif has
      become a common peptide tag in chemical biology.

PMID- 30091483
TI  - Effects of crowding and water restriction stress on creole goat reproduction in
      the Oaxacan Sierra Mixteca, Mexico.
AB  - Chronic stress disrupts reproductive efficiency. Yet, the manner in which stress
      disturbs reproduction in goats is currently unknown. The Oaxacan Mixteca region
      is one of Mexico's poorest, with high levels of deforestation, high ambient
      temperatures, and lack of water. Native goats of the Oaxacan Mixteca Region live
      in these stressful conditions, as well as in overcrowded and water restricted
      conditions. Therefore, the aim of this study was to evaluate the effects of these
      very stressful conditions on the reproduction of male and female goats. Control
      group was uncrowded, with daily water supply; stress group was overcrowded, with
      water restriction. The study was conducted from September 2015 to February 2016;
      the expression of reproductive behaviour and variations of cortisol levels were
      assessed. In females, oestradiol and progesterone were evaluated during the
      oestrous cycle. In males, testosterone levels were evaluated before and during
      reproductive activity. Sexual behaviour decreased in stressed goats: approaching,
      tail swishing, urination, vaginal discharge and flank contraction decreased in
      stressed females. Anogenital sniffing, licking, Flehmen reflex, bleating, mount
      attempts and mounts decreased in male goats. Cortisol levels in stressed animals
      were higher compared with control animals. Oestradiol and Progesterone levels in
      stressed females were significantly lower during the follicular and luteal phase,
      respectively, compared with control females. Testosterone levels in stressed
      males were lower than in control males, both before and during reproduction.
      These results indicate that even though goats from the Oaxacan Mixteca Region are
      habituated to their environmental conditions, they are still stressed by them, as
      shown by a higher activation of the adrenal axis in stressed goats than in
      control goats. High cortisol levels may induce low oestradiol levels in females
      and low testosterone levels in males, as well as a disruption in the expression
      of their reproductive behaviour.

PMID- 30091484
TI  - Raising the Working Temperature of a Triboelectric Nanogenerator by Quenching
      Down Electron Thermionic Emission in Contact-Electrification.
AB  - As previously demonstrated, contact-electrification (CE) is strongly dependent on
      temperature, however the highest temperature in which a triboelectric
      nanogenerator (TENG) can still function is unknown. Here, by designing and
      preparing a rotating free-standing mode Ti/SiO2 TENG, the relationship between CE
      and temperature is revealed. It is found that the dominant deterring factor of CE
      at high temperatures is the electron thermionic emission. Although it is normally
      difficult for CE to occur at temperatures higher than 583 K, the working
      temperature of the rotating TENG can be raised to 673 K when thermionic emission
      is prevented by direct physical contact of the two materials via preannealing.
      The surface states model is proposed for explaining the experimental phenomenon.
      Moreover, the developed electron cloud-potential well model accounts for the CE
      mechanism with temperature effects for all types of materials. The model
      indicates that besides thermionic emission of electrons, the atomic thermal
      vibration also influences CE. This study is fundamentally important for
      understanding triboelectrification, which will impact the design and improve the
      TENG for practical applications in a high temperature environment.

PMID- 30091485
TI  - Outsourcing in Iranian hospitals: Findings from a qualitative study.
AB  - Outsourcing is used as a strategy to improve efficiency, quality, and
      satisfaction of beneficiaries in hospitals. This study aimed to determine the
      reasons for outsourcing, outsourced services, achieved objectives, and
      outsourcing challenges. This qualitative study was conducted through 58 face-to
      face semi-structured interviews with chief executive officers (CEOs), chief
      financial officers (CFOs), and contracting experts (CEs) in 42 public hospitals
      in Tehran, Iran. Purposive and snowball sampling techniques were used. Interviews
      were recorded digitally and transcribed verbatim. Data analysis was performed
      based on an inductive-deductive approach via MAXQDA-10. The Participants included
      26 CEOs, 15 CFOs, and 17 CEs. The most important reasons for outsourcing were
      divided into four main categories including financial resources and funding,
      customers, management, and factors related to the hospitals. Accessing to up-to
      date knowledge and technology, improving service quality and accountability,
      focusing on strategic points, reducing workload, and increasing patient
      satisfaction turned out to be the positive outcomes of outsourcing. Weakness in
      laws and regulations, monitoring and assessment of an outsourced unit, creating
      dependency and changing organizational culture, as well as human resource issues
      were introduced as the main pitfalls and challenges of outsourcing. Based on the
      results, it was suggested that the hospital managers must attempt to outsource
      services by realistic analysis of the organization's current status. They should
      specify the reasons and objectives of outsourcing and make decisions based on
      outsourcing potentials. By taking the current challenges of outsourcing in
      Iranian hospitals into account, the authorities can make the most efficient
      decisions with regard to outsourcing.

PMID- 30091486
TI  - Spirofused and Annulated 1,2,4-Trioxepane-, 1,2,4-Trioxocane-, and 1,2,4
      Trioxonane-Cyclohexadienones: Cyclic Peroxides with Unusual Ring Conformation
      Dynamics.
AB  - C3- or C4-hydroxyalkylated phenols are highly reactive towards peroxidation with
      oxone, which results in the formation of tertiary C3 hydroperoxides. This
      reaction can also be performed with photochemically generated singlet oxygen.
      However, other characteristic singlet oxygen reactions do not proceed with
      caroate. The initially formed hydroperoxides cyclize in the presence of a Lewis
      acid catalyst based on boron, indium, or iron to give spiroannulated peroxides.
      These exhibit restricted ring inversion whereas larger nine-membered-ring
      peroxides are thermally less stable and show higher ring flexibility (according
      to NMR analysis).

PMID- 30091487
TI  - Enhancing policy implementation to improve healthcare practices: The role and
      strategies of hybrid national-local support structures.
AB  - BACKGROUND: In this study, we followed a national initiative to enhance the use
      of quality indicators gathered in national quality registries (NQRs) for
      improvement of clinical practices in Swedish healthcare, more specifically by
      investigating the support strategies of regional support centers with national
      and local missions. The aim was to increase knowledge on the role, challenges,
      and strategies of support structures with mixed and complex missions in the
      healthcare system. METHODS: Documents and 25 semistructured interviews with staff
      at 6 regional support centers, ie, quality registry centers, formed this multiple
      case study. Data were analyzed using conventional content analysis. RESULTS: The
      centers' strategies varied from developing the NQRs to become more suitable for
      improvement to supporting healthcare's use of NQRs, from the use of task to
      process-oriented support strategies, and from taking on national responsibilities
      to responding to local initiatives. All quality registry centers engaged in
      initiatives inspired by the Breakthrough Series approach. Some used preexisting
      change concepts or collaborated with local development units. A main challenge
      was to overcome a lack of formal mandate to act in the healthcare organizations
      they served. CONCLUSIONS: Support functions with mixed and complex missions have
      to use a variation of strategies to reach relevant actors and achieve changes.
      This study provides valuable input for policy and decision-makers on the support
      strategies used and challenges of support functions with complex missions
      situated in-between national and local levels of the healthcare system, here
      denoted hybrid national-local support structures.

PMID- 30091488
TI  - Charge Accumulation and Multi-Electron Photoredox Chemistry with a Sensitizer
      Catalyst-Sensitizer Triad.
AB  - Photoinduced electron transfer in donor-sensitizer-acceptor compounds usually
      leads to simple electron-hole pairs, and photoredox catalysis typically relies on
      single-electron transfer (SET) events. This work reports on a molecular triad
      able to accumulate two electrons on a central dibenzo[1,2]dithiin moiety flanked
      by two peripheral RuII photosensitizers. Under continuous illumination, the
      doubly reduced form of the dibenzo[1,2]dithiin undergoes thiolate-disulfide
      exchange with an aliphatic disulfide substrate, thereby acting as a two-electron
      catalyst after two initial SET events with triethylamine at the RuII sensitizers.
      The use of a relatively simple triad for coupling two separate SET processes to a
      subsequent two-electron reduction is an important conceptual advance from
      photoinduced SET and light-driven charge accumulation towards multi-electron
      photoredox catalysis. This is relevant for artificial photosynthesis and light
      driven multi-electron chemistry in general.

PMID- 30091489
TI  - Selective C-O Coupling Hidden in the Thermal Reaction of [Al2 CuO5 ]+ with
      Methane.
AB  - The thermal gas-phase reaction of [Al2 CuO5 ]+ with methane has been explored by
      using FT-ICR mass spectrometry complemented by high-level quantum chemical
      calculations. The generation of atomic [Cu]+ from the [Al2 CuO5 ]+ /CH4 couple
      corresponds to the only reaction channel. Labeling experiments and computational
      studies strongly suggest that methane activation is indeed involved in the
      production of [Cu]+ , and generation of CH2 O prevails. Mechanistic aspects and
      the associated doping effects are discussed.

PMID- 30091490
TI  - "Thrust out of normality"-How adults living with cystic fibrosis experience
      pulmonary exacerbations: A qualitative study.
AB  - AIM AND OBJECTIVES: To explore the experience of pulmonary exacerbation from the
      perspective of adults with cystic fibrosis. BACKGROUND: While management of
      pulmonary exacerbations is a pillar of cystic fibrosis care, little is known of
      patients' perspectives. Understanding the patient's experience is essential for
      developing and evaluating interventions in support of patient self-management.
      DESIGN: Qualitative study with longitudinal study in a subsample. METHODS: The
      study took place from 2015-2016 in a university hospital. Eighteen patients with
      cystic fibrosis were included who were >=18 years of age and had no solid organ
      transplant. Patients' experiences were explored through semistructured interviews
      and analysed using framework analysis. They each participated in one interview,
      with a subsample (N = 7) being interviewed twice during and once after antibiotic
      therapy. RESULTS: Patients (11 men and 7 women; median age 29.5 years, range 19
      55 years; median FEV1 45%, range FEV1 23%-105%) experienced pulmonary
      exacerbations as disruptions of their normality, which led to a substantial
      increase in their emotional distress. Exacerbations represented a period of
      threat and domination by CF; that is, symptoms and treatment consumed energy,
      restricted physical activity and daily life roles. "Noting change," "waiting
      until antibiotics help," "returning to normality" and "establishing a new
      normality" characterised their descriptions of the pulmonary exacerbation
      trajectory. Emotional distress was the major driver for patients' self
      management, and personal goals and illness beliefs influenced also patients' self
      management decisions. CONCLUSION: The experienced degree and source of emotional
      distress are drivers for self-management decisions in patients with cystic
      fibrosis who experience a pulmonary exacerbation. RELEVANCE TO CLINICAL PRACTICE:
      Our data provide new understanding that will be essential to informing clinical
      practice, future patient-reported outcomes measures and intervention development.

PMID- 30091491
TI  - Gender medicine in dilated cardiomyopathy: pride and prejudice.

PMID- 30091492
TI  - Prolyl hydroxylases positively regulated LPS-induced inflammation in human
      gingival fibroblasts via TLR4/MyD88-mediated AKT/NF-kappaB and MAPK pathways.
AB  - OBJECTIVES: Prolyl hydroxylases (PHDs) play essential roles in oxygen-sensing
      system, whereas the effects of PHDs on inflammation have not been totally
      uncovered. Our study aimed to investigate the role of PHDs in lipopolysaccharide
      (LPS)-induced inflammation of human gingival fibroblasts (HGFs) and clarify the
      potential mechanisms. MATERIALS AND METHODS: A pan hydroxylase inhibitor,
      dimethyloxallyl glycine (DMOG), and RNA interference were used to explore the
      role of PHDs in inflammation. Cytotoxic effect of DMOG was determined by cell
      counting kit-8 and flow cytometry respectively. The secretion levels of IL-6 and
      IL-8 were assessed by ELISA. The mRNA levels of inflammatory cytokines, Toll-like
      receptor (TLR) 4 and MyD88 were evaluated by quantitative real-time PCR. The
      activation of NF-kappaB, mitogen-activated protein kinase (MAPK) and PI3K/AKT
      pathways were detected by western blot and the nuclear translocation of NF-kappaB
      p65 was examined by immunofluorescence. Downregulation of PHD1 and PHD2 was
      performed with siRNA transfection. RESULTS: Dimethyloxallyl glycine inhibited LPS
      induced inflammatory cytokine, TLR4 and MyD88 expression in gene level and the
      elevated secretion of IL-6 and IL-8 was also downregulated. Additionally, LPS
      induced activation of NF-kappaB, MAPK and AKT pathways was abolished by DMOG
      treatment. Importantly, LPS-induced inflammatory cytokine expression was merely
      suppressed by PHD2 knockdown. CONCLUSIONS: Prolyl hydroxylases acted as a
      positive regulator in LPS-induced inflammation of HGFs via TLR4/MyD88-mediated NF
      kappaB, MAPK and AKT signalling pathways and PHD2 among three isoforms was
      principally responsible for the effects.

PMID- 30091493
TI  - "You'll have to be my eyes and ears": A conversation analytic study of physical
      examination on a health helpline.
AB  - AIMS AND OBJECTIVES: To explore the accomplishment of physical examination on a
      health helpline. By focusing on the ways in which callers are asked to examine
      themselves and report information to nurses, we aim to provide insight into how
      physical examination at a distance is achieved. BACKGROUND: Physical examination
      is a routine feature of healthcare encounters. In face-to-face settings, patients
      are subject to professional scrutiny through talk, touch and observation. Health
      professionals working on helplines face challenges in assessing signs of illness
      when they do not have physical access to patients. DESIGN AND METHODS:
      Conversation analysis was used to explore sequences of interaction between nurses
      and callers that involved physical examination. ANALYSIS: Analysis examined how
      physical examination was routinely accomplished in a helpline environment. Nurses
      typically guided callers in self-examination by drawing on gross categorisations
      that required reporting of large-scale characteristics of symptoms (e.g., whether
      a body part looked "normal"). Physical examination was also regularly
      accomplished by nurses through two-component speaking turns: a prefacing
      component that involved instructions about self-examination; followed by a second
      component that included an information-soliciting question. These practices
      resulted in callers successfully accomplishing physical examination, despite
      their lack of professional medical knowledge. CONCLUSIONS: This study identifies
      the communicative practices used by nurses to accomplish physical examination in
      helpline calls. Such practices involved asking questions that sought general,
      rather than specific, information and the prefacing of questions with simple
      instructions on how to undertake self-examination. RELEVANCE TO CLINICAL
      PRACTICE: Previous research indicates that physical examination in telehealth can
      be challenging, particularly in environments where clinicians need patients to
      examine themselves. This study identifies how nurses on a helpline manage this
      challenge. The findings highlight ways in which nurses can recruit patients to
      undertake tasks that would typically be undertaken by clinicians in physically co
      present consultations.

PMID- 30091494
TI  - Patients' perspectives on engaging in their healthcare while hospitalised.
AB  - AIMS AND OBJECTIVES: To examine patients' experiences and preferences for
      engaging in their healthcare while hospitalised. BACKGROUND: Promoting patient
      engagement or involvement in healthcare has become an important component of
      contemporary, consumer-oriented approaches to quality care. Previous research on
      patient engagement highlights that preferences for engagement are not assessed
      while hospitalised, leading to patient role confusion and frustration. METHODS:
      Semistructured interviews were conducted with patients from January-March 2017 to
      examine their experiences and preferences for engaging in their care while
      hospitalised on medical-surgical units in the United States. Inductive thematic
      analysis was used to uncover the themes from the interview transcriptions. The
      reporting of research findings followed the COREQ checklist. RESULTS: Seventeen
      patients, eight male and nine female, aged between 19-83 years old were
      interviewed. Patients had a difficult time articulating how they participated in
      their care while hospitalised, with the majority stating there were few decisions
      to be made. Many patients felt that decisions were made prior to or during
      hospitalisation for them. Patients described their engagement through the
      following themes: sharing the subjective, involvement of family, information
      gathering, constraints, "I let them take care of me," and variability.
      CONCLUSIONS: Engagement is a dual responsibility of both nurses and patients.
      Patients' experiences highlight that engagement preferences and experiences are
      not universal between patients, speaking to the importance of assessing patient
      preferences for engagement in health care upon hospital admission. RELEVANCE TO
      CLINICAL PRACTICE: The articulation of what patients actually experience in the
      hospital setting contributes to improve nursing practice by offering insight into
      what is important to the patient and how best to engage with them in their care.
      The constraints that patients reported facing related to their healthcare
      engagement should be used to inform the delivery of future engagement
      interventions in the acute care setting.

PMID- 30091495
TI  - A modified developmental care bundle reduces pain and stress in preterm infants
      undergoing examinations for retinopathy of prematurity: A randomised controlled
      trial.
AB  - AIMS AND OBJECTIVES: To determine the comparative efficacy of developmental care
      versus standard care for reducing pain and stress in preterm infants during
      examinations for retinopathy of prematurity (ROP). BACKGROUND: ROP examinations
      are routinely performed in neonatal intensive care units to detect these lesions.
      Pain scores recorded during and after eye examinations have revealed
      physiological and behavioural manifestations of pain and stress. DESIGN: A
      randomised crossover trial was conducted. METHODS: Fourteen preterm infants were
      evaluated. The modified developmental care bundle included environmental
      modifications, positioning and containment, oxygen supplementation, interaction
      and approach and cue-based individual care, which were applied before, during and
      after the ROP examination. The primary outcomes were obtained from pain and
      stress scores using the premature infant pain profile-revised (PIPP-R) and a
      behavioural evaluation. The secondary outcomes were recovery time to the baseline
      of the vital signs and oxygen saturation. RESULTS: Statistical significances were
      found in the care type comparison (p = 0.013), time comparison (p < 0.001) and
      type-by-time interaction (p = 0.005) in the PIPP-R, and also in the care type
      comparison (p < 0.001), time comparison (p < 0.001) and type-by-time interaction
      (p = 0.001) in the behavioural evaluation scores using a generalised estimating
      equation (GEE) analysis. Recovery time for the developmental care (N = 13, mean =
      8.6 +/- 11.5 min, 95% CI = 1.68-15.57) was significantly shorter than for the
      standard care (N = 11, mean = 25.5 +/- 20.8 min, 95% CI = 11.45-39.46), which was
      found to be statistically significant according to the Wilcoxon signed-rank test
      (N = 11, p = 0.003). CONCLUSIONS: A bundled developmental care intervention
      significantly reduced pain and stress responses and the time needed for infants
      to recover their physiological status following the procedure. RELEVANCE TO
      CLINICAL PRACTICE: Since the results show the benefits of developmental care in
      an ROP examination, it can be the practical evidence basis by which to develop a
      standard of procedure or guideline for clinical practice.

PMID- 30091496
TI  - Mentoring up: A grounded theory of nurse-to-nurse mentoring.
AB  - AIMS AND OBJECTIVES: To generate a theoretical explanation of nurse-to-nurse
      mentoring in the clinical setting. BACKGROUND: Despite an abundance of mentoring
      literature, the processes involved between nurses in mentoring relationships have
      yet to be studied. Nursing literature has focused on mentor attributes and
      relationship outcomes rather than focusing on theoretical discovery. DESIGN:
      Classical grounded theory (CGT). METHODS: CGT procedures (constant comparative
      method, coding and memoing) were used to analyse interview data exploring fifteen
      nurse proteges' experiences of mentoring. RESULTS: Confidencing, the proteges'
      need to become confident in the professional role, emerged as the main concern of
      study participants. Three dimensions are threaded throughout nurse-to-nurse
      mentoring: earnest intentions, filial bond and trust-worthiness. Earnest
      intentions are the sincere attitude that proteges and mentors demonstrate
      regarding their mentoring relationship. An exclusive, familial-type connection,
      filial bond, attends to the affective needs of proteges and mentors. Trust
      worthiness, the explicit feeling of trust between proteges and mentors,
      strengthens as each demonstrates being worthy of the other's trust. Mentoring Up
      theory explains five phases of mentoring: seeding, opening, laddering, equalising
      and reframing. The initial phases are periods of relationship discovery (seeding)
      and testing (opening). Laddering is an intense period of reciprocal interactions
      between mentors and proteges. Equalising begins as proteges perceive themselves
      to be equal to their mentors in terms of their professional capability. Proteges
      reflect on the meaning of the relationship in the reframing phase. CONCLUSIONS:
      Mentoring Up is a dense theory that reveals insights, explanations and
      predictions for initiating, developing and engaging in mentoring relationships.
      Mentoring Up fills a gap in the existing literature and provides a framework for
      future mentoring research. RELEVANCE TO CLINICAL PRACTICE: The theory has
      implications for healthcare organisations, nursing education and individual
      nurses. Mentoring Up expounds on the interpersonal connections and reciprocal
      interactions vital for successful nurse-to-nurse mentoring.

PMID- 30091497
TI  - Retrospective chart review to assess domains of quality of death (recognition of
      dying, appropriate limitations, symptom monitoring, anticipatory prescribing) of
      patients dying in the acute hospital under the care of a Nephrology service with
      RSC support over time.
AB  - AIM: To explore the quality of deaths in the acute hospital under a Nephrology
      service at two teaching hospitals in Sydney with Renal Supportive Care services
      over time. METHODS: Retrospective chart review of all deaths in the years 2004,
      2009 and 2014 at St George Hospital (SGH) and in 2014 at Concord Repatriation
      General Hospital (CRGH). Domains assessed were recognition of dying, invasive
      interventions, symptom assessment, anticipatory prescribing, documentation of
      spiritual needs and bereavement information for families. End of Life Care Plan
      (EOLCP) use was also evaluated at SGH. RESULTS: Over 90% of patients were
      recognised to be dying in all 3 years at SGH. Rates of interventions in the last
      week of life were low and did not differ across the three years. There was a
      significant increase in prescription of anti-psychotic, and anti-emetic, and anti
      cholinergic medication over the years at SGH. Use of EOLCPs was significantly
      higher at SGH, and their use improved several quality domains. 68% of all deaths
      were referred to Palliative care at SGH, 33% at CRGH (ns). Cessation of
      observations and non-essential medications, and documentation of bereavement
      information given to families was low across both sites in all years, although
      significantly improved when EOLCPs were used. CONCLUSION: While acute teams are
      good at recognising dying, they need support to care for dying patients. The use
      of EOLCPs in acute services can facilitate improvements in caring for the dying.
      RSC services need time to become embedded in the culture of the acute hospital.
      This article is protected by copyright. All rights reserved.

PMID- 30091498
TI  - Medication adherence assessment practices in dialysis settings: A survey of renal
      nurses' perceptions.
AB  - AIMS AND OBJECTIVES: To measure renal nurses' perceptions on assessing medication
      adherence in patients undergoing dialysis. BACKGROUND: Renal nurses play a vital
      role in caring for patients undergoing dialysis. Despite the high prevalence of
      medication nonadherence in chronic dialysis patients, little is known about renal
      nurses' perceptions and current adherence assessment practices. DESIGN: A cross
      sectional survey. METHODS: Participants completed an online survey between March
      May 2016. Five psychometric scales were used to measure perception on prevalence
      and contributors of nonadherence, effective methods of assessment, barriers to
      assessment and confidence to assess adherence. The survey also captured current
      adherence assessment practices using a 4-point graded response (1 = do not
      practice at all to 4 = practice for every patient). RESULTS: A total of 113
      dialysis nurses completed the survey. The majority agreed that patients in their
      unit are nonadherent to their medicines (74.5%, n = 82; median = 8). Most nurses
      agreed that having dedicated professionals conducting medication history
      interviews can be effective in identifying nonadherence (88.9%, n = 96; median =
      8). Objective assessment through blood results was the most frequently used
      method to determine nonadherence (83.2%, n = 89), with little attention being
      paid to patients' self-reports of adherence (55.1%, n = 59). Time constraints,
      administrative support and patients' disinterest in discussing medication-related
      issues with the nurses were perceived as barriers to assessing adherence.
      CONCLUSIONS: Patient self-reported measures to assess adherence were
      underutilised by the renal nurses, whereas objective blood monitoring was
      routinely used. Overcoming dialysis nurses' work-related barriers may facilitate
      the effective monitoring and promotion of medication adherence in chronic
      dialysis patients. RELEVANCE TO CLINICAL PRACTICE: Results from this study
      emphasise the need for proper assessment of dialysis patient's medication-taking
      behaviour during routine dialysis to ensure the benefits of prescribed therapies.

PMID- 30091499
TI  - Perceived added value of a decision support App for formal caregivers in
      community-based dementia care.
AB  - AIMS AND OBJECTIVES: To gain insight into the perceived added value of a decision
      support App for district nurses and case managers intended to support a problem
      assessment and the provision of advices on possible solutions to facilitate
      ageing in place of people with dementia, and to investigate how they would
      implement the App in daily practice. BACKGROUND: District nurses and case
      managers play an important role in facilitating ageing in place of people with
      dementia (PwD). Detecting practical problems preventing PwD from living at home
      and advising on possible solutions is complex and challenging tasks for nurses
      and case managers. To support them with these tasks, a decision support App was
      developed. METHODS: A qualitative study using semi-structured interviews was
      conducted. A photo-elicitation method and an interview guide were used to
      structure the interviews. The data were analysed according to the principles of
      content analysis. RESULTS: In five interviews with seven district nurses and case
      managers, the added value was described in terms of five themes: (a) providing a
      broader/better overview of possible solutions; (b) providing a
      guideline/checklist for problem assessment and advice on solutions; (c)
      supporting an in-depth problem assessment; (d) being a support tool for
      unexperienced case managers/district nurses; and (e) providing up-to-date
      information. The participants regarded the App as complementary to their current
      work procedure, which they would use in a flexible manner at different stages in
      the care continuum. CONCLUSIONS: The participants valued both parts, the problem
      assessment and the overview of possible solutions. An important requisite for the
      usage would be that the content is continuously updated. Before implementation of
      the App can be recommended, an evaluation of its effectiveness regarding decision
      making should be conducted. RELEVANCE TO CLINICAL PRACTICE: This study underpins
      the need of nurses and case managers for decision support with regard to problem
      assessment and providing advices on possible solutions to facilitate ageing in
      place of PwD. There results also show the importance of listening to users
      experience and their perceived added value of decision support tools as this
      helps to explain the lack of statistically significant effects on quantitative
      outcome measure in contrast to a high willingness to use the App in a previous
      study.

PMID- 30091501
TI  - The self-care coping process in patients with chronic heart failure: A
      qualitative study.
AB  - AIM: To understand the self-care coping process among chronic heart failure
      patients. BACKGROUND: Previous studies have been carried out to understand the
      experience and the challenges of living with chronic heart failure. However, the
      coping processes that patients use to overcome self-care challenges are less
      understood. DESIGN: A qualitative design with qualitative content analysis of
      data was employed. METHODS: Purposive sampling was conducted to recruit
      inpatients with chronic heart failure between March 1, 2014-March 1, 2015, in a
      teaching hospital in Taiwan. Semi-structured interviews (N = 27) were completed,
      and a content analysis was performed using an inductive method to explore the
      self-care coping processes in patients with chronic heart failure. RESULTS: The
      findings were categorised into three themes: (a) responding to chronic heart
      failure self-care (dealing with negative emotions, accepting reality and
      struggling between a self-care regime and self preference), (b) finding ways to
      live with chronic heart failure (enhancing understanding and knowledge about
      chronic heart failure, maintaining outer and inner self, engaging
      positively/negatively with others and relying on religious thoughts and seeking
      consolation) and (c) reinterpreting chronic heart failure and performing meaning
      oriented coping (re-evaluating the meaning of life, assigning a new perspective
      for chronic heart failure and discovering a deeper meaning behind it).
      CONCLUSION: Self-appearance concerns should be given more attention by healthcare
      professionals. Meaning-oriented coping was found to be helpful to cope with the
      challenges of chronic heart failure. Thus, there is a need to develop
      interventions associated with meaning-oriented coping to enhance coping
      strategies for chronic heart failure patients. RELEVANCE TO CLINICAL PRACTICE: It
      is suggested for healthcare professionals to understand an individual's coping
      process and support people with chronic heart failure who struggle with self-care
      coping. Furthermore, specific interventions including meaning-oriented
      interventions might benefit people with chronic heart failure to cope more
      successfully.

PMID- 30091500
TI  - Tetrahedral DNA nanostructures facilitate neural stem cell migration via
      activating RHOA/ROCK2 signalling pathway.
AB  - OBJECTIVES: The main purpose of current study was to explore the effects of
      tetrahedral DNA nanostructures (TDNs) on neuroectodermal (NE-4C) stem cells
      migration and unveil the potential mechanisms. MATERIALS AND METHODS: The
      successfully self-assembled TDNs were also determined by dynamic light scattering
      (DLS). A bidirectional wound-healing assay and transwell chamber assay were
      employed to test the migrating behaviour of NE-4C stem cells cultured under
      different conditions. RESULTS: Through an in vitro study, we found that stem
      cells could internalize TDNs quickly, and the cells' parallel and vertical
      migration was promoted effectively. Besides, the effects of TDNs were found being
      exerted by upregulating the gene and protein expression levels of RhoA, Rock2 and
      Vinculin, indicating that the RHOA/ROCK2 pathway was activated by the TDNs during
      the cell migration. CONCLUSIONS: In conclusion, TDNs could enter NSCs without the
      aid of other transfection reagents in large amounts, whereas only small amounts
      of ssDNA could enter the cells. TDNs taken up by NSCs activated the RHOA/ROCK2
      signalling pathway, which had effects on the relevant genes and proteins
      expression, eventually promoting the migration of NE-4C stem cells. These
      findings suggested that TDNs have great potential in application for the repair
      and regeneration of neural tissue.

PMID- 30091503
TI  - Helicobacter pylori antimicrobial resistance in a pediatric population.
AB  - BACKGROUND: The increasing prevalence of Helicobacter pylori (H. pylori)
      antimicrobial resistance, primarily for clarithromycin decreases the success of
      treatment. The aim of this study is to determine the local pattern of first-line
      antimicrobials resistance and the eradication rate. MATERIAL AND METHODS:
      Prospective cohort study of H. pylori infected patients (positive histological or
      cultural exams) treated at Centro Materno-Infantil do Norte from January of 2013
      to October of 2017. Susceptibility to 4 antibiotics: amoxicilin, metronidazole,
      clarithromycin, and levofloxacin were analyzed by E-test (phenotypic resistance).
      The E-test was chosen because it is simple and cost-effective for routine
      susceptibility testing. Point mutations that confer clarithromycin resistance
      were surveyed (genotypic resistance). Eradication of H. pylori infection was
      defined by a negative urea breath test or fecal antigen 6-8 weeks after the end
      of treatment. RESULTS: Of a total of 74 H. pylori infected patients, 16 were
      excluded because they had previous H. pylori treatment or severe systemic
      disease. Median age of infection cases was 15 years (3-17 years). Eradication
      regimen used in all patients combined the use of 3 antibiotics (amoxicillin and
      metronidazole or clarithromycin) and proton pump inibhitor for 14 days and was
      tailored according antimicrobial susceptibility. 79.5% of the patients completed
      the treatment. The resistance rate for metronidazole and clarithromycin was 3.3%
      and 23.3%, respectively. There was no resistance for amoxicilin and levofloxacin.
      The rate of genotypic resistance to clarithromycin was 37.2%. The eradication
      rate was 97.8%. CONCLUSIONS: The authors found a high resistance rate of H.
      pylori for clarithromycin in this northern portuguese pediatric center. This
      factor should determine a change in local current treatment, contraindicating the
      use of clarithromycin as a first-line treatment for H. pylori infection in
      children. The high eradication rate maybe explained for the eradication treatment
      tailored according antimicrobial susceptibility.

PMID- 30091502
TI  - Dermatophytic pseudomycetomas in two ferrets (Mustela putorius furo).
AB  - BACKGROUND: Dermatophytic pseudomycetoma is an atypical form of dermatophytosis
      where the infection is located in the deep dermal and subcutaneous tissues.
      Although rare, it is most commonly associated with Microsporum canis or
      Trichophyton sp. It has been reported in cats, dogs and horses. OBJECTIVES: To
      describe the clinical and pathological findings of dermatophytic pseudomycetoma
      caused by M. canis and Trichophyton sp. in two domestic ferrets. ANIMALS: Two pet
      ferrets (Mustela putorius furo). METHOD AND MATERIALS: Case report. RESULTS: Two
      ferrets were diagnosed with dermatophytic pseudomycetoma confirmed by
      histological examination of tissue and fungal culture. In both cases, ferrets
      presented with several cutaneous firm nodules 0.6-3 cm in diameter. Microscopic
      lesions revealed multifocal nodular pyogranulomatous inflammation with
      intralesional fungi. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the
      authors' knowledge, this is the first description of dermatophytic pseudomycetoma
      in domestic ferrets. This disease should be included in the differential
      diagnosis of nodular dermatopathies in this species.

PMID- 30091504
TI  - Modular Functionalization of Arenes in a Triply Selective Sequence: Rapid C(sp2 )
      and C(sp3 ) Coupling of C-Br, C-OTf, and C-Cl Bonds Enabled by a Single
      Palladium(I) Dimer.
AB  - Full control over multiple competing coupling sites would enable straightforward
      access to densely functionalized compound libraries. Historically, the site
      selection in Pd0 -catalyzed functionalizations of poly(pseudo)halogenated arenes
      has been unpredictable, being dependent on the employed catalyst, the reaction
      conditions, and the substrate itself. Building on our previous report of C-Br
      selective functionalization in the presence of C-OTf and C-Cl bonds, we herein
      complete the sequence and demonstrate the first general arylations and
      alkylations of C-OTf bonds (in <10 min), followed by functionalization of the C
      Cl site (in <25 min), at room temperature using the same air- and moisture-stable
      PdI dimer. This allowed the realization of the first general and triply selective
      sequential C-C coupling (in 2D and 3D space) of C-Br followed by C-OTf and then C
      Cl bonds.

PMID- 30091505
TI  - Silane coatings of metallic biomaterials for biomedical implants: A preliminary
      review.
AB  - In response to increased attention in literature, this work provides a
      qualitative review surrounding the application of silane-based coatings of
      metallic biomaterials for biomedical implants. Included herein is both a brief
      summary of existing knowledge and concepts regarding silane-based thin films,
      along with an analysis of recent peer-reviewed publications and advances towards
      their practical application for biomedical coatings. Specifically, the review
      identifies innovative silane-based coatings according to their molecular identity
      and film structure and analyses their impact on the biocorrosion resistance,
      protein adsorption, cell viability, and antimicrobial properties of the overall
      coated implant. It is shown that a range of common silanes clearly exhibit
      promising properties for biomedical implant coatings, but further work is needed,
      particularly on mechanisms of physiological interaction and characteristic
      effects of silane functional groups, before seeing clinical use. (c) 2018 Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2901-2918,
      2018.

PMID- 30091506
TI  - Mentalization-based treatment and its evidence-base status: A systematic
      literature review.
AB  - PURPOSE: This study reviewed the evidence-base status of mentalization-based
      treatment (MBT), its quality, strengths, and limitations. The aim was to pave the
      way for further MBT research. METHOD: An electronic database and reference lists
      search identified MBT outcome papers, and these were systematically reviewed. The
      quality of the studies and the risk of bias were determined using two validated
      checklist tools. RESULTS: Twenty-three studies were included in the review. This
      included nine randomized controlled trials, seven uncontrolled pre- and post
      effectiveness studies, three retrospective cohort studies, two uncontrolled
      randomized trials, and two case studies. The methodological quality of almost
      half of the papers was assessed as fair (43%), followed by good (34%), poor
      (17%), and excellent (4%) ratings. Nevertheless, the review identified risk of
      confounding bias across the majority of studies (60%) and fidelity to treatment
      was poorly reported in almost half of the studies (47%). Most of the studies
      focused on borderline personality disorder (BPD), showing positive clinical
      outcomes for this population but the evidence-base for other presentations was
      still developing. The treatment of adolescents who self-harm and at-risk mothers
      in substance abuse treatment showed particularly promising results, as these are
      client groups that have previously shown limited positive response to
      psychological interventions. CONCLUSIONS: Mentalization-based treatment is a
      potentially effective method across a wide range of clinical presentations but
      further research should focus on increasing the quality and the quantity of the
      MBT evidence outside the treatment of BPD. PRACTITIONER POINTS: MBT can be a
      particularly effective intervention for the treatment of adults with a diagnosis
      of BPD and of adolescents who self-harm and mothers enrolled in substance abuse
      treatments. MBT can be an effective intervention for depression and eating
      disorders but the evidence is currently limited. Professionals supporting mothers
      of children at risk may benefit from receiving training in the principles of MBT.

PMID- 30091507
TI  - Discriminatory Value of the Ascending Aorta Diameter in Suspected Acute Type A
      Aortic Dissection.
AB  - OBJECTIVE: The objective was to determine if ascending aorta (AscAo) diameters
      measured by noncontrast computed tomography (CT) allow for meaningful
      discrimination between patients with and without type A aortic dissection (TAAD),
      ideally with 100% sensitivity. METHODS: This study was a retrospective analysis
      of cases of TAAD, as well as controls, undergoing evaluation for TAAD with CT
      aortography, presenting to 21 emergency departments within an integrated health
      system between 2007 and 2015. AscAo diameters were determined using axial
      noncontrast CT images at the level of the right main pulmonary artery by two
      readers. AscAo diameters were additionally normalized for age, sex, and body
      surface area (assessed by a Z-score, which is the number of standard deviations
      between the observed and expected AscAo diameters). Overall model discrimination
      was assessed using the area under the receiver operating characteristic curve
      (AUC). Comparative discrimination was assessed using both the change in AUC
      (?AUC) and the continuous net reclassification index (NRI). RESULTS: A total of
      230 cases of TAAD and 325 controls were included in the study. The median ages
      for cases and controls were 65 and 62 years, and the median AscAo diameters were
      50 and 35 mm, respectively. The raw and normalized AscAo diameters demonstrated
      similarly excellent discrimination (AUCs of 0.96 vs. 0.97, respectively; ?AUC =
      0.01, p = 0.09) and an NRI of 0.30 (95% confidence interval [CI] = 0.13-0.47),
      both indicating small incremental improvements in classification with the use of
      the normalized AscAo measures. A raw AscAo diameter of 34 mm and a normalized Z
      score of 1.84 both yielded 100% sensitivity for TAAD, with respective
      specificities of 35% (95% CI = 29.6%-40.2%) and 67% (95% CI = 61.7%-72.2%).
      CONCLUSIONS: Nearly all patients with TAAD appear to have enlarged AscAo
      diameters as measured by noncontrast CT, whereas most patients with suspected but
      absent TAAD have relatively normal AscAo diameters. Both raw and normalized AscAo
      measures provided relatively comparable discriminatory value. If validated, these
      data may be useful in adjudicating risk among patients with suspected TAAD in
      whom a criterion standard test is unavailable, nondiagnostic, or contraindicated.

PMID- 30091508
TI  - Serum cathelicidin as a marker for diabetic nephropathy in patients with type 1
      diabetes.
AB  - BACKGROUND: The aim of the study was to evaluate the relationship between serum
      cathelicidin level and diabetic nephropathy (DN) in patients with type 1 diabetes
      mellitus (T1DM). METHODS: The study group consisted of 76 patients with T1DM (47
      men), aged 36 +/- 7 years, and with duration of T1DM 14 (7-18) years. Serum
      cathelicidin was measured by ELISA test in healthy controls (n = 20) and in 76
      T1DM patients grouped as follows: G1 = patients with normal urinary albumin
      excretion (n = 20), G2 = patients with microalbumin excretion (n = 19), G3 =
      patients with macroalbumin excretion but normal serum creatinine level (n = 19),
      and G4 = patients with macroalbumin excretion with increased serum creatinine (n
      = 18). RESULTS: There was no significant difference in serum cathelicidin levels
      between healthy controls and G1 diabetic patients, but serum levels were
      progressively increased from the stage of microalbuminuria to frank nephropathy
      (P < .001). Positive correlation between serum cathelicidin level and the
      presence of DN, thyroid-stimulating hormone, total cholesterol, and negative with
      male sex and fasting plasma glucose, was found. In multiple regression analysis,
      serum cathelicidin level was associated with the presence of DN after adjustment
      of sex, waist-to-hip ratio, total cholesterol, and thyroid-stimulating hormone.
      CONCLUSIONS: Patients with T1DM and DN are characterized by increased serum
      cathelicidin level. There was an independent relationship between serum
      cathelicidin level and DN. Serum cathelicidin level can be used as an early
      marker for the presence and progression of DN in T1DM patients.

PMID- 30091509
TI  - Impact of simulated MitraClip on forward flow obstruction in the setting of
      mitral leaflet tethering: An in vitro investigation.
AB  - OBJECTIVES: We aimed to evaluate diastolic leaflet tethering as a factor that may
      cause mitral stenosis (MS) after simulated MitraClip implantation, using an in
      vitro left heart simulator. BACKGROUND: Leaflet tethering commonly seen in
      functional mitral regurgitation may be a significant factor affecting the
      severity of MS after MitraClip implantation. METHODS: A left heart simulator with
      excised ovine mitral valves (N = 6), and custom edge-to-edge clip devices
      (GTclip) was used to mimic implantation of MitraClip in a variety of positions.
      Anterior mitral leaflet (AML) tethering severity was varied for each case
      (leaflet excursion of 75 degrees , 60 degrees , and 45 degrees , consistent with
      mild, moderate and severe tethering), and the baseline mitral annular area (MAA)
      was varied across samples (3.6-4.8 cm2 ). The resulting mitral valve area (MVA),
      and peak/mean mitral valve gradient (MVG) were measured in each case. RESULTS:
      AML tethering severity was a highly significant factor increasing MVG and
      decreasing MVA (P < 0.001). When GTclip placement was simulated with severe AML
      tethering, mean MVG >5 mmHg resulted more frequently than with GTclip placement
      alone (46% vs. 4%, respectively). However, severe AML tethering alone
      significantly reduced baseline MVA to 3.6 +/- 0.2 cm2 , and increased baseline
      MVG to 3.0 +/- 0.4 mmHg. At MAA above 4.7 cm2 , severe AML tethering did not
      cause moderate MS, even with placement of two GTclips (95% confidence).
      CONCLUSIONS: Our results show that diastolic AML tethering may predispose to MS
      after clip placement, however, MS was not observed when baseline MVA was above
      4.0 cm2 . Severity of AML tethering may be an important criterion in selecting
      patients for edge-to-edge repair.

PMID- 30091510
TI  - Surface patterning of a novel PEG-functionalized poly-l-lactide polymer to
      improve its biocompatibility: Applications to bioresorbable vascular stents.
AB  - Today, research in the field of bioresorbable vascular stents (BVS) not only
      focusses on a new material being nontoxic but also tries to enhance its
      biocompatibility in terms of endothelialization potential and hemocompatibility.
      To this end, we used picosecond laser ablation technology as a single-step and
      contactless method for surface microstructuring of a bioresorbable polymer which
      can be utilized in stent manufacture. The method works on all materials via fast
      material removal, can be easily adapted for micropatterning of tubular or more
      complex sample shapes and scaled up by means of micropatterning of metal molds
      for manufacturing. Here, picosecond laser ablation was applied to a
      bioresorbable, biologically inactive and polyethylene glycol-modified poly-L
      lactide polymer (PEGylated PLLA) to generate parallel microgrooves with varying
      geometries. The different patterns were thoroughly evaluated by a series of cyto-
      and hemocompatibility tests revealing that all surfaces were non-toxic and non
      hemolytic. More importantly, patterns with 20 to 25 um wide and 6 to 7 um deep
      grooves significantly enhanced endothelial cell adhesion in comparison to samples
      with smaller grooves. Here, human cardiac microvascular endothelial cells were
      found to align along the groove direction, which is thought to encourage
      endothelialization of intraluminal surfaces of BVS. (c) 2018 The Authors Journal
      of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley
      Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000, 2018.

PMID- 30091511
TI  - Nitrogen Codoped Unique Carbon with 0.4 nm Ultra-Micropores for Ultrahigh Areal
      Capacitance Supercapacitors.
AB  - A full understanding of ion transport in porous carbon electrodes is essential
      for achieving effective energy storage in their applications as electrochemical
      supercapacitors. It is generally accepted that pores in the size range below 0.5
      nm are inaccessible to electrolyte ions and lower the capacitance of carbon
      materials. Here, nitrogen-doped carbon with ultra-micropores smaller than 0.4 nm
      with a narrow size distribution, which represents the first example of electrode
      materials made entirely from ultra-microporous carbon, is prepared. An in situ
      electrochemical quartz crystal microbalance technique to study the effects of the
      ultra-micropores on charge storage in supercapacitors is used. It is found that
      ultra-micropores smaller than 0.4 nm are accessible to small electrolyte ions,
      and the area capacitance of obtained sample reaches the ultrahigh value of 330 uF
      cm-2 , significantly higher than that of previously reported carbon-based
      materials. The findings provide a better understanding of the correlation between
      ultra-micropore structure and capacitance and open new avenues for design and
      development of carbon materials for the next generation of high energy density
      supercapacitors.

PMID- 30091512
TI  - Evaluation of resorbable polydioxanone and polyglycolic acid meshes in a rat
      model of ventral hernia repair.
AB  - The objective of this study was to evaluate physical, mechanical, and biological
      properties of the polydioxanone (PDO) monofilament meshes and polyglycolide (PGA)
      polyfilament meshes in comparison with Permacol(r) implants. In rat experimental
      model, a 1.5 * 2.0 cm defect in abdominal wall was reconstructed by using the
      Permacol surgical implant or knitted meshes produced from either PDO
      monofilament, or PGA multifilament. The implant sites were assessed for the
      tensile strength and the extents of material resorption, host inflammatory
      response and host tissue replacement on days 3, 10, 30, or 60 after the surgery.
      The PDO and PGA meshes were rapidly pervaded by the host connective tissue with
      elements of skeletal muscle histogenesis. The degree of adhesions was
      significantly higher in the Permacol group. All of the prostheses underwent
      resorption, which correlated with gradual decreases in the overall tensile
      strength of the site and the Col1a1 gene expression level. Elevated expression of
      Fgf2 gene maintained longer in the PDO group, and the Mmp9 gene expression level
      in this group was higher than in the other groups. Gene expression levels of
      inflammatory cytokines were higher in the Permacol group. The foreign body giant
      cell numbers were lower in the PDO and Permacol groups than in the PGA group.
      Minimal macrophage infiltration with predominance of M2 cells was observed in the
      PDO group. Overall, the PDO prosthesis turned out to be significantly better than
      the PGA or Permacol prostheses by a number of indicators of biocompatibility and
      efficacy. (c) 2018 The Authors Journal of Biomedical Materials Research Part B:
      Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part
      B: Appl Biomater 00B: 000-000, 2018.

PMID- 30091513
TI  - Nanoentrapped polyphenol coating for sustained drug release from a balloon
      catheter.
AB  - Peripheral artery disease is a cardiovascular disease characterized by a
      narrowing of arteries that supply blood to the extremities, particularly, the
      legs. When surgical intervention is warranted, the primary approach is balloon
      angioplasty. Drug coated balloons (DCB) designed to release antimitogenic agents
      to the site of the blockage are a relatively new product aimed at reducing artery
      re-narrowing, or restenosis, after intervention. However, first generation DCB
      utilize mainly direct application of the chemotherapy drug paclitaxel, along with
      hydrophilic excipients to facilitate uptake into the tissue, and the majority of
      drug is released from the DCB systemically. We thus designed a drug-eluting
      nanoparticle delivery system for firm attachment to the balloon surface and only
      slow release of its entrapped drugs within a fluid environment. We furthermore
      chose the relatively nontoxic polyphenols resveratrol and quercetin as active
      agents we've shown reduce smooth muscle cell proliferation and inflammatory cell
      and platelet activation, all contributing events in restenosis. A polymeric
      nanoparticle (pNP) system based on poly(lactic-co-glycolic) acid but possessing a
      positive charge was designed for firm attachment to the balloon matrix, followed
      by adhesion to the negatively charged bilayer of the vascular wall. As a first
      step toward testing its biologic properties, drug elution into a simulated blood
      fluid was determined, as well as the fold enrichment of cells with drug after
      exposure to the drug-entrapped pNPs compared to drugs only. Cytotoxicity to
      vascular smooth muscle cells was assessed, along with their biocompatibility,
      determined as their ability to promote red blood cell lysis. The drug-entrapped
      pNP system showed excellent biocompatibility with limited cytotoxicity. In
      addition, the pNPs released the two drugs only very slowly over 10 days.
      Development of a spray process for delivering the drug-entrapped pNPs to a
      balloon surface and in vivo testing in small animals appears warranted. (c) 2018
      Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 00B: 000-000,
      2018.

PMID- 30091514
TI  - Development of calcium phosphate/ethylene glycol dimethacrylate particles for
      dental applications.
AB  - This study describes the synthesis of dicalcium phosphate dihydrate (DCPD)
      particles in the presence of different ethylene glycol dimethacrylates (EGDMA,
      ethylene glycol/EG units: 1, 2, 3 or 4) at two monomer-to-ammonium phosphate
      molar ratios (1:1 and 2:1), as a strategy to develop CaP-monomer particles with
      improved interaction with resin matrices. Particles displaying high surface areas
      and organic contents were added to a photocurable BisGMA-TEGDMA resin and the
      resulting materials were tested for degree of conversion (DC), biaxial flexural
      strength (BFS), flexural modulus, and ion release. Data were subjected to one-way
      ANOVA or Kruskal-Wallis/Dunn test (alpha: 0.05). Functionalization with EGDMA
      derivatives was dependent upon the length of the spacer group and monomer
      concentration in the synthesis. No differences in DC were observed among
      materials (p > 0.05). A 39% increase in BFS was obtained with the use of
      particles with the highest functionalization level compared to non-functionalized
      particles (p < 0.001). The use of functionalized DCPD reduced flexural modulus in
      comparison to non-functionalized particles (p < 0.001). Calcium release was
      similar among materials and remained constant during the experiment, while
      phosphate release was higher at 7 days in comparison to the remaining weeks (p <
      0.001). In conclusion, diethylene glycol dimethacrylate resulted in the highest
      functionalization levels and the highest BFS among DCPD-containing materials. Ion
      release was not affected by functionalization. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 30091515
TI  - Comparison of polyetheretherketone versus silicon nitride intervertebral spinal
      spacers in a caprine model.
AB  - Polyetheretherketone (PEEK) is commonly used as a spinal spacer for
      intervertebral fusion surgery. Unfortunately, PEEK is bioinert and does not
      effectively osseointegrate into living bone. In contrast, comparable spacers made
      of silicon nitride (Si3 N4 ) possess a surface nanostructure and chemistry that
      encourage appositional bone healing. This observational study was designed to
      compare the outcomes of these two biomaterials when implanted as spacers in an
      adult caprine model. Lumbar interbody fusion surgeries were performed at two
      adjacent levels in eight adult goats using implants of PEEK and Si3 N4 . At six
      months after surgery, the operative and adjacent spinal segments were extracted
      and measured for bone fusion, bone volume, bone-implant contact (BIC) and soft
      tissue implant contact (SIC) ratios, and biodynamic stability. The null
      hypothesis was that no differences in these parameters would be apparent between
      the two groups. Fusion was observed in seven of eight implants in each group with
      greater bone formation in the Si3 N4 group (52.6%) versus PEEK (27.9%; p = 0.2).
      There were no significant differences in BIC ratios between PEEK and Si3 N4 , and
      the biodynamic stability of the two groups was also comparable. The results
      suggest that Si3 N4 spacers are not inferior to PEEK and they may be more
      effective in promoting arthrodesis. (c) 2018 Wiley Periodicals, Inc. J Biomed
      Mater Res Part B: Appl Biomater 00B: 000-000, 2018.

PMID- 30091517
TI  - Information-seeking and use of information resources among melanoma patients of
      German skin cancer centers.
AB  - BACKGROUND: This study aimed to explore the information-seeking behavior (ISB) of
      melanoma patients (MPs) and MP subgroups, in order to provide data for needs
      based adaptation of information provision. METHODS: In a cross-sectional survey
      in 27 German skin cancer centers, we explored characteristics of the ISB of MPs
      with the aid of a standardized questionnaire. Sub-group differences were
      determined with the chi-squared test and predictors of media preferences with
      logistic regression. RESULTS: 67 % of the 529 participating MPs had clinical
      stage III or IV melanoma. Most of the participants (81 %) reported medical
      consultations as their regularly or frequently used information resource (IR). 58
      % wished to have more advice about IRs from their physician. Only 8 % of MPs used
      the services of self-help groups and 12 % of MPs took advantage of the services
      of cancer counseling centers. The internet (63 %) and booklets (58 %) were
      reported to be the preferred media. Age, educational level, general need for
      information and lack of awareness of their own condition proved to be predictors
      for media preferences. CONCLUSIONS: Most MPs expected their physician to advise
      them about IRs they could use in addition to medical consultations. Peer support
      services were quite underused by MPs. The various preferences of media by MPs
      should be considered when deve-loping and providing IRs.

PMID- 30091516
TI  - Diverse Excretion Pathways of Benzyl Glucosinolate in Humans after Consumption of
      Nasturtium (Tropaeolum majus L.)-A Pilot Study.
AB  - SCOPE: Different metabolic and excretion pathways of the benzyl glucosinolate
      breakdown products benzyl isothiocyanate and benzyl cyanide are investigated to
      obtain information about their multiple fate after ingestion. Detailed focus is
      on the so far underestimated transformation/excretion pathways-protein
      conjugation and exhalation. METHODS AND RESULTS: Metabolites, protein conjugates,
      and non-conjugated isothiocyanates are determined in plasma, urine, and breath of
      seven volunteers after consuming freeze-dried nasturtium or bread enriched with
      nasturtium. Samples are collected up to 48 h at selected time points. The
      metabolites of the mercapturic acid pathway are detectable in plasma up to 24 h
      after consumption. Additionally, mercapturic acid is the main metabolite in
      urine, but non-conjugated benzyl isothiocyanate is detectable as well. Protein
      conjugates show high amounts in plasma even 48 h after consumption. In breath,
      benzyl isothiocyanate and benzyl cyanide are detectable up to 48 h after
      consumption. CONCLUSION: Isothiocyanates are not only metabolized via the
      mercapturic acid pathway, but also form protein conjugates in blood and are
      exhaled. To balance intake and excretion, it is necessary to investigate all
      potential metabolites and excretion routes. This has important implications for
      the understanding of physiological and pharmacological effects of isothiocyanate
      containing products.

PMID- 30091518
TI  - Enzymatically Powered Surface-Associated Self-Motile Protocells.
AB  - Cell motility is central to processes such as wound healing, immune cell
      surveillance, and embryonic development. Motility requires the conversion of
      chemical to mechanical energy. An active area of research is to create motile
      particles, such as microswimmers, using catalytic and enzymatic reactions. Here,
      autonomous motion is demonstrated in adhesive polymer-based protocells by
      incorporating and harnessing the energy production of an enzymatic reaction.
      Biotinylated polymer vesicles that encapsulate catalase, an enzyme which converts
      hydrogen peroxide to water and oxygen, are prepared and these vesicles are
      adhered weakly to avidin-coated surfaces. Upon addition of hydrogen peroxide,
      which diffuses across the membrane, catalase activity generates a differential
      impulsive force that enables the breakage and reformation of biotin-avidin bonds,
      leading to diffusive vesicle motion resembling random motility. The random
      motility requires catalase, increases with the concentration of hydrogen
      peroxide, and needs biotin-avidin adhesion. Thus, a protocellular mimetic of a
      motile cell.

PMID- 30091519
TI  - Recurrent ulceronecrotic plaques and nodules with spontaneous remission.

PMID- 30091520
TI  - Use of Cellutome for the healing of venous or mixed ulcers.
AB  - Venous or mixed ulcers are common and invalidating. Cutaneous transplants may be
      necessary if conventional treatment is ineffective. We evaluated the performance
      of Cellutome in promoting the healing of venous or mixed ulcers 2 months after
      grafting. This was a retrospective, multi-centric, descriptive study of patients
      who had a venous or mixed ulcer for at least several months and who received an
      autologous skin graft using the Cellutome system at least 2 months before. The
      principle evaluation criterion was the state of the wound after 2 months
      (completely healed vs not healed). The secondary evaluation criterion was the
      percentage of wound healing after 2 months. A total of 47 patients were included
      in the study. The ulcers had evolved over an average of 18 months. The average
      surface area was 13.37 cm2 . After 2 months, the grafts of 26 of 47 patients
      (55.3%) were completely healed. The grafts of 21 patients (44.6%) were not
      completely healed but showed an average rate of healing of 51%. Use of the
      Cellutome system for epidermal transplants promoted complete or improved healing
      after 2 months for 55.3% of patients with chronic venous or mixed ulcers. The
      limited data on the rate of healing of conventional transplants in the literature
      report rates of approximately 50%. The Cellutome system may therefore be of
      interest as the healing rate is similar to that of conventional techniques, but
      using a much simpler, painless procedure on an outpatient basis.

PMID- 30091521
TI  - Treatment of inflammatory linear verrucous epidermal nevus pruritus with
      thalidomide.

PMID- 30091522
TI  - Itraconazole encapsulated PLGA-nanoparticles covered with mannose as potential
      candidates against leishmaniasis.
AB  - Leishmaniasis is a neglected disease threatening over 350 million people.
      Antimonials are first-line drugs due to resistance and side effects there is a
      demand for alternative chemotherapy. Itraconazole (ITZ) is an antimycotic. It was
      encapsulated into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and
      covered with mannose. The NPs were 250 nm and -1.1 mV +/- 0.7. PLGA-ITZ-mannose
      NPs presented a toxicity of 20.7% for J774 cells, and no toxicity for THP 1. The
      J774 cells were infected with three Leishmania promastigotes strains and treated
      with ITZ loaded PLGA NPs with/without mannose. The parasite percentage of L.(V.)
      panamensis intracellular amastigotes significantly (p < 0.01) decreased from
      34.4% to 13.7% and 5.7% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively.
      For L.(L.) infantum there was a reduction (p < 0.001) from 18.1% to 4.8% and 8.3%
      for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. Further with L.(L.)
      braziliensis amastigotes there was a significant reduction (p < 0.001) from 54.9%
      to 28% and 21.1% for PLGA-ITZ-mannose NPs and PLGA-ITZ NPs, respectively. Adding
      mannose increased the efficacy PLGA-ITZ NPs against L.(L.) infantum, while it had
      no effect against L(V.) panamensis and L.(L.) braziliensis amastigotes. We
      recommend further investigation of PLGA-ITZ-mannose NPs in animal models to
      evaluate their potential. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res
      Part B: Appl Biomater 00B: 000-000, 2018.

PMID- 30091523
TI  - UV Photodetectors Based on BiOCl Nanosheet Arrays: The Effects of Morphologies
      and Electrode Configurations.
AB  - A facile chemical bath method is adopted to grow bismuth oxychloride (BiOCl)
      nanosheet arrays on a piece of Cu foil (denoted as BiOCl-Cu) and isolated BiOCl
      nanosheets are collected by ultrasonication. A self-supporting BiOCl film is
      obtained by the removal of Cu foil. Photodetectors (PDs) based on these BiOCl
      materials are assembled and the effects of morphologies and electrode
      configurations on the photoelectric performance of these PDs are examined. The
      BiOCl nanosheet PD achieves high responsivities in the spectral range from 250 to
      350 nm, while it presents quite a small photocurrent and slow response speed. The
      BiOCl film PD yields low photocurrents and near-unity on-off ratios,
      demonstrating poor photoelectric performance. The photocurrent of the BiOCl-Cu PD
      with both electrodes on the BiOCl film is much higher than those of these above
      mentioned PDs, and the response times are fast. Meanwhile, the BiOCl-Cu PD with
      separate electrodes on the BiOCl film and Cu foil achieves even higher
      photocurrents and presents a self-powering characteristic, depicting the improved
      photodetecting performances induced by the specific morphology and distinct
      electrode configuration. These results would promote the applications of BiOCl
      nanostructures in the photoelectric devices.

PMID- 30091524
TI  - GraftFast Surface Engineering to Improve MOF Nanoparticles Furtiveness.
AB  - Controlling the outer surface of nanometric metal-organic frameworks (nanoMOFs)
      and further understanding the in vivo effect of the coated material are crucial
      for the convenient biomedical applications of MOFs. However, in most studies, the
      surface modification protocol is often associated with significant toxicity
      and/or lack of selectivity. As an alternative, how the highly selective and
      general grafting GraftFast method leads, through a green and simple process, to
      the successful attachment of multifunctional biopolymers (polyethylene glycol
      (PEG) and hyaluronic acid) on the external surface of nanoMOFs is reported. In
      particular, effectively PEGylated iron trimesate MIL-100(Fe) nanoparticles (NPs)
      exhibit suitable grafting stability and superior chemical and colloidal stability
      in different biofluids, while conserving full porosity and allowing the
      adsorption of bioactive molecules (cosmetic and antitumor agents). Furthermore,
      the nature of the MOF-PEG interaction is deeply investigated using high
      resolution soft X-ray spectroscopy. Finally, a cell penetration study using the
      radio-labeled antitumor agent gemcitabine monophosphate (3 H-GMP)-loaded MIL
      100(Fe)@PEG NPs shows reduced macrophage phagocytosis, confirming a significant
      in vitro PEG furtiveness.

PMID- 30091526
TI  - The use of heparin, bFGF, and VEGF 145 grafted acellular vascular scaffold in
      small diameter vascular graft.
AB  - We aim to test the application of heparin, bFGF, and VEGF 145 grafted acellular
      vascular scaffold in small diameter vascular graft. The amount of bFGF and VEGF
      145 were determined by ELISA. Femoral artery transplantation was performed.
      Mechanical strength of acellular vascular scaffolds was determined. Angiography
      was performed for blood vessel patency. Factor VIII and alpha2-actin expression
      was detected by immunohistochemistry. bFGF and VEGF 145 had stable release at 60
      and 70 days in vitro, and the release rate of VEGF 145 was slightly slower than
      that of bFGF. After transplantation, 9 months of the vascular patency rate was
      100% at 1, 3, and 9 months, and, was up to 90% at 18 months, while the patency
      rate in group with grafted heparin only at 1-month was 60%, at 3-month was 40%,
      at 9-month was 15%, and at 18-month was 10%. The blood vessels taken after 18
      months had no significant difference in the mechanical properties between the
      transplanted and the natural vessels. Positive expression of factor VIII and
      alpha2-actin was observed. The heparinized and bFGF and VEGF 145 grafted
      allogeneic vascular acellular scaffolds are preliminarily obtained, which show
      good biocompatibility and patency and are of great importance for small diameter
      vascular graft. (c) 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl
      Biomater 00B: 000-000, 2018.

PMID- 30091525
TI  - Stretchable Transparent Conductive Films from Long Carbon Nanotube Metals.
AB  - Flexible transparent conductors are an enabling component for large-area flexible
      displays, wearable electronics, and implantable medical sensors that can wrap
      around and move with the body. However, conventional conductive materials decay
      quickly under tensile strain, posing a significant hurdle for functional flexible
      devices. Here, we show that high electrical conductivity, mechanical
      stretchability, and optical transparency can be simultaneously attained by
      compositing long metallic double-walled carbon nanotubes with a
      polydimethylsiloxane substrate. When stretched to 100% tensile strain, thin films
      incorporating these long nanotubes (~3.2 um on average) achieve a record high
      conductivity of 3316 S cm-1 at 100% tensile strain and 85% optical transmittance,
      which is 194 times higher than that of short nanotube controls (~0.8 um on
      average). Moreover, the high conductivity can withstand more than 1000 repeated
      stretch-release cycles (switching between 100% and 0% strain) with a retention
      approaching 96%, whereas the short nanotube controls exhibit only 10%.
      Mechanistic studies reveal that long tubes can bridge the microscale gaps
      generated during stretching, thereby maintaining high electrical conductivity.
      When mounted on human joints, this elastic transparent conductor can accommodate
      large motions to provide stable, high current output. These results point to
      transparent conductors capable of attaining high electrical conductivity and
      optical transmittance under mechanical strain to allow large shape changes that
      may take place in the operation and use of flexible electronics.

PMID- 30091528
TI  - Deep surgical site infection after ankle fractures treated by open reduction and
      internal fixation in adults: A retrospective case-control study.
AB  - Information on ankle fractures is limited. The purpose of this study was to
      investigate the incidence and risk factors for deep surgical site infection
      (DSSI) after open reduction and internal fixation (ORIF). Adult patients who
      underwent ORIF for an ankle fractures at 3 level-I centres between January 2013
      and June 2017 were included. Data on demographic, injury-related, and surgery
      related variables and biochemical indexes from the laboratory were collected from
      patients' electronic medical records. Univariate analysis and multivariate
      logistic regression analysis model were used to perform the data analysis through
      SPSS 19.0. Within 1-year postoperatively, 2.83% (74/2617) of cases developed
      DSSI, with the earliest occurring at the 4th and latest at 147th day. Pseudomonas
      aeruginosa, methicillin-resistant Staphylococcus aureus, and methicillin
      susceptible Staphylococcus aureus were the top 3 bacteria, causing 73% (37/51) of
      all the cases. Age (45-64 and >=65 years), current smoking status, chronic heart
      disease, lower preoperative albumin level, open injury, and prolonged surgical
      duration were identified to be independently associated with DSSI occurrence.
      Preoperative active supplementation of nutrition, immediate smoking cessation,
      and optimisation of an operative plan for the reduction of surgical duration were
      feasible measures for DSSI prevention following ORIF of ankle fractures.

PMID- 30091529
TI  - Label-free non-linear microscopy to measure myelin outcome in a rodent model of
      Charcot-Marie-Tooth diseases.
AB  - Myelin sheath produced by Schwann cells covers and nurtures axons to speed up
      nerve conduction in peripheral nerves. Demyelinating peripheral neuropathies
      result from the loss of this myelin sheath and so far, no treatment exists to
      prevent Schwann cell demyelination. One major hurdle to design a therapy for
      demyelination is the lack of reliable measures to evaluate the outcome of the
      treatment on peripheral myelin in patients but also in living animal models. Non
      linear microscopy techniques which include second harmonic generation (SHG),
      third harmonic generation (THG) and coherent anti-stokes Raman scattering (CARS)
      were used to image myelin ex vivo and in vivo in the sciatic nerve of healthy and
      demyelinating mice and rats. SHG did not label myelin and THG required too much
      light power to be compatible with live imaging. CARS is the most reliable of
      these techniques for in vivo imaging and it allows for the analysis and
      quantification of myelin defects in a rat model of CMT1A disease. This
      microscopic technique therefore constitutes a promising, reliable and robust
      readout tool in the development of new treatments for demyelinating peripheral
      neuropathies.

PMID- 30091527
TI  - Nomenclature for factors of the HLA system, update May 2018.

PMID- 30091531
TI  - The Alkanes with Maximum Wiener Polarity Index.
AB  - The Wiener polarity index (usually denoted by Wp ) of an alkane is the number of
      unordered pairs of carbon atoms which are separated by three carbon-carbon bonds.
      This topological index Wp is useful for predicting the boiling points of alkanes.
      Deng [MATCH Commun. Math. Comput. Chem. 66 (2011) 305] proved that the maximum Wp
      value among all alkanes, with n carbon atoms, is 3n-15 . The main purpose of
      present paper is to find all those alkanes with n carbon atoms, which attain the
      maximum value of Wp .

PMID- 30091532
TI  - Noninvasive assessments of skin glycated proteins by fluorescence and Raman
      techniques in diabetics and nondiabetics.
AB  - Diabetes is a complex metabolic disease and has chronic complications. It has
      been considered a serious public health problem. The aim of the current study was
      to evaluate skin glycated proteins through fluorescence and Raman techniques. One
      hundred subjects were invited to participate in the study. Six volunteers did not
      attend due to exclusion criteria or a change of mind about participating.
      Therefore, 94 volunteers were grouped according to age range (20-80 years),
      health condition (nondiabetic, with insulin resistance [IR] and/or diabetic) and
      Fitzpatrick skin type (I-VI). The fluorescence spectrometer and the portable
      Raman spectroscopy system were used to measure glycated proteins from the skin.
      There was elevated skin autofluorescence in healthy middle-aged and elderly
      subjects, as well as in patients with IR and/or diabetes. Regarding Raman
      spectroscopy, changes in the skin hydration state, degradation of type I collagen
      and greater glycation were related for diabetes and chronological aging. Weak and
      positive correlation between the skin autofluorescence and the Raman peaks ratio
      (855/876) related to the glycated proteins was also found. Raman spectroscopy
      shows several bands for spectral analyses, complementing the fluorescence data.
      Therefore, this study contributes to understanding of the optical of human skin
      for noninvasive diabetes screening.

PMID- 30091530
TI  - ING5-mediated antineuroblastoma effects of suberoylanilide hydroxamic acid.
AB  - Neuroblastoma is the most common extracranial solid neuroendocrine cancer and is
      one of the leading causes of death in children. To improve clinical outcomes and
      prognosis, discovering new promising drugs and targeted medicine is essential. We
      found that applying Suberoylanilide hydroxamic acid (SAHA; Vorinostat, a histone
      deacetylase inhibitor) and MG132 (a proteasome inhibitor) to SH-SY5Y cells
      synergistically suppressed proliferation, glucose metabolism, migration, and
      invasion and induced apoptosis and cell cycle arrest. These effects occurred both
      concentration and time dependently and were associated with the effects observed
      with inhibitor of growth 5 (ING5) overexpression. SAHA and MG132 treatment
      increased the expression levels of ING5, PTEN, p53, Caspase-3, Bax, p21, and p27
      but decreased the expression levels of 14-3-3, MMP-2, MMP-9, ADFP, Nanog, c-myc,
      CyclinD1, CyclinB1, and Cdc25c concentration dependently, similar to ING5. SAHA
      may downregulate miR-543 and miR-196-b expression to enhance the translation of
      ING5 protein, which promotes acetylation of histones H3 and H4. All three
      proteins (ING5 and acetylated histones H3 and H4) were recruited to the promoters
      of c-myc, Nanog, CyclinD1, p21, and p27 for complex formation, thereby regulating
      the mRNA expression of downstream genes. ING5 overexpression and SAHA and/or
      MG132 administration inhibited tumor growth in SH-SY5Y cells by suppressing
      proliferation and inducing apoptosis. The expression of acetylated histones H3
      and ING5 may be closely linked to the tumor size of neuroblastomas. In summary,
      SAHA and/or MG132 can synergistically suppress the malignant phenotypes of
      neuroblastoma cells through the miRNA-ING5-histone acetylation axis and via
      proteasomal degradation, respectively. Therefore, the two drugs may serve as
      potential treatments for neuroblastoma.

PMID- 30091534
TI  - The use of direct immunofluorescence and nested polymerase chain reaction in
      diagnosing perinatal infections of Chlamydia trachomatis.
AB  - BACKGROUND: Chlamydia infection is the most frequently reported infectious,
      sexually transmitted disease (STD). Generally, Chlamydia trachomatis (C.
      trachomatis) infection of neonates is the result of perinatal exposure to the
      mother's infected cervix. OBJECTIVES: The aim of the study was to estimate the
      frequency of infection caused by C. trachomatis in newborn infants. In this study
      of C. trachomatis perinatal infection, 107 infants born at the Wroclaw Medical
      University Clinic of Gynecology and Obstetrics (Poland) were tested to
      investigate whether C. trachomatis was present in swabs taken from the eyes and
      throats of children. MATERIAL AND METHODS: Each specimen was tested using the
      direct immunofluorescence test (DIF) and the nested polymerase chain reaction
      (PCR) method. RESULTS: The presence of C. trachomatis, irrespective of the origin
      of the swabs (ocular or from the throat), was confirmed in 62 newborns, amounting
      to 57.6% of the tested population. The occurrence of C. trachomatis in ocular
      swabs was confirmed in 35 children (32.7%). In the material taken from the
      throat, there were 48 newborns considered chlamydia-positive (44.9%). In the
      specimens taken from both the ocular and pharyngeal locations, there was a higher
      proportion of positive results while using the nested-PCR method in comparison to
      the DIF test. The specificity of the DIF method with reference to the nested-PCR
      was 67.9% for ocular swabs. In the material taken from the throat, the
      sensitivity of the DIF method with reference to the nested-PCR was 75.0% and the
      specificity was 62.1%. CONCLUSIONS: Because of the importance of perinatal
      infections, it is recommended to perform a study among a larger group of patients
      in order to gain more reliable results.

PMID- 30091533
TI  - Demystifying the Flow: Biocatalytic Reaction Intensification in Microstructured
      Enzyme Reactors.
AB  - Continuous (flow) reactors have drawn a wave of renewed interest in biocatalysis.
      Many studies find that the flow reactor offers enhanced conversion efficiency.
      What the reported reaction intensification actually consists in, however, often
      remains obscure. Here, a canonical microreactor design for heterogeneously
      catalyzed continuous biotransformations, featuring flow microchannels that
      contain the enzyme immobilized on their wall surface are examined. Glycosylations
      by sucrose phosphorylase are used to assess the potential for reaction
      intensification due to microscale effects. Key variables are identified, and
      their corresponding relationship equations, to describe, and optimize, the
      interplay between reaction characteristics, microchannel geometry and reactor
      operation. The maximum space-time-yield (STY_max) scales directly with the enzyme
      activity immobilized on the available wall surface. Timescale analysis, comparing
      the characteristic times of reaction (taureac ) and diffusion (taudiff ) to the
      mean residence time (taures ), reveals operational conditions for optimum reactor
      output. Theoretical insight into determinants of microreactor performance is
      applied to biocatalytic syntheses of alpha-d-glucose 1-phosphate and alpha
      glucosyl glycerol. Process boundaries for enzyme showing, respectively, high (80
      U mg-1 ) and low (4 U mg-1 ) specific activities are thus established and options
      for process design revealed. Opportunities, and limitations, of the application
      of principles of microscale flow chemistry to biocatalytic transformations are
      made evident.

PMID- 30091535
TI  - Determination of the concentration of cathepsin B by SPRI biosensor in children
      with appendicitis, and its correlation with proteasomes.
AB  - BACKGROUND: Cathepsin B (CatB) belongs to a family of lysosomal cysteine
      proteases and plays an important role in intracellular proteolysis. OBJECTIVES:
      The concentration of CatB and 20S proteasome was evaluated in the serum of
      children with appendicitis, before and after surgery, on a basis of an innovative
      method for determining biomolecules concentration - surface plasmon resonance
      imaging (SPRI) biosensor. MATERIAL AND METHODS: Forty-two children with acute
      appendicitis, who were treated at the Department of Pediatric Surgery (Medical
      University of Bialystok, Poland), were randomly included into the study (age: 5
      17 years, mean age: 11.5 +/-1 year). There were 15 girls and 27 boys in the study
      group. Eighteen healthy, age-matched subjects, admitted for planned surgeries,
      served as controls. Exclusion criteria were the following: severe preexisting
      infections, immunological or cardiovascular diseases that required longterm
      medication, and complicated cases of appendicitis with perforation of the
      appendix and/or peritonitis. RESULTS: The CatB concentrations in the blood plasma
      of patients with acute appendicitis were elevated before surgery, they were the
      highest 24 h after surgery, and were above the range of concentrations measured
      in controls; the difference was statistically significant. The CatB concentration
      measured 72 h after the operation was decreased, but still did not reach the
      normal range when compared with the concentration measured in controls (p <
      0.05). CONCLUSIONS: Cathepsin B concentration may reflect the metabolic response
      to acute state of inflammation, surgical intervention in the abdominal cavity and
      the process of gradual ebbing of the inflammation. The method of operation -
      classic open appendectomy or laparoscopic appendectomy - does not influence the
      general trend in the CatB concentration in children with appendicitis. There is a
      strong positive correlation between the CatB and 20S proteasome concentrations 24
      h after surgery. The SPRI method can be successfully used for determining the
      concentration of active forms of enzymes presented in lysosomes in the diagnosis
      of inflammatory conditions in the abdominal cavity.

PMID- 30091536
TI  - Assessment of the FTO gene polymorphisms in male patients with metabolic
      syndrome.
AB  - BACKGROUND: Accumulating evidence indicates the potential involvement of the FTO
      gene polymorphisms in the etiology of metabolic syndrome (MetS) and related
      disorders. OBJECTIVES: In this study, we aimed to investigate whether the FTO
      gene polymorphisms are associated with the risk of MetS and its simple components
      in a homogeneous sample of males. MATERIAL AND METHODS: Anthropometric and
      biochemical parameters were assessed in 192 males. A total of 100 males met the
      National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII)
      criteria for a diagnosis of MetS. The following FTO gene polymorphisms were
      genotyped: rs1421085, rs17817449, rs1558902, and rs9939609. RESULTS: There were
      significant differences between participants with distinct rs9939609 genotypes
      with respect to waist-to-hip ratio (WHR) and the levels of total cholesterol.
      Individuals with the rs1421085 CC genotype had significantly higher levels of
      triglycerides compared to those with other corresponding genotypes. Participants
      with the rs1558902 AA genotype had significantly higher body mass index (BMI),
      WHR, as well as the levels of total cholesterol and triglycerides. There were no
      significant differences in genotype distribution allelic frequencies of all
      tested polymorphisms between individuals with MetS and control subjects.
      CONCLUSIONS: Our results indicate that the genetic variation in the FTO gene
      might be related to single metabolic disturbances. However, the FTO gene
      polymorphisms are not associated with the risk of MetS.

PMID- 30091537
TI  - [Electroacupuncture of "Zusanli" (ST 36) Raises Muscular Force by Adjusting
      AMPK/PGC-1 alpha Signaling in Rats with Chronic Fatigue Syndrome].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Zusanli" (ST 36)
      on mitochondrial oxidative stress of skeletal muscle in rats with chronic fatigue
      syndrome (CFS) based on adenosine 5'-monophosphate (AMP)-activated protein kinase
      (AMPK)/ peroxlsome proliferator-activated receptor-gamma coactivator-1 alpha (PGC
      1 alpha) signaling, in order to reveal its mechanism underlying improvement of
      CFS. METHODS: Forty SD rats were randomly divided into normal control, CFS model,
      EA-Zusanli (ST 36) and EA-non-acupoint groups (n=10 rats in each group). The CFS
      model was established by forced exhausted load-bearing swimming (twice daily),
      chronic constraint (1 h) and sleep deprivation (20 h/day) for 14 days. Following
      modeling, EA (2 Hz/100 Hz, 2 V) was applied to bilateral Zusanli (ST 36) or non
      acupoint (about 10-15 mm superior to the bilateral Iliac creast and about 20 mm
      lateral to the posterior median line) for 20 min, once a day for 10 days. The
      expression levels of ATP synthase, AMPK, phosphorylated (p)-AMPK, silent mating
      type information regulation 2 homolog-1 (SIRT 1) and PGC-1 alpha proteins, and
      ATP synthase, SIRT 1 and PGC-1 alpha mRNAs of the quadriceps femoris muscle were
      detected by Western blot and fluorescence quantitative PCR, respectively. The
      rats' grabbing force was detected by using a grabbing-force detector. RESULTS:
      Compared with the normal group, the grabbing force, and the expression levels of
      ATP synthase and PGC-1 alpha proteins and mRNAs were significantly decreased
      (P<0.05, P<0.01), while the expression of SIRT 1 protein was significantly up
      regulated (P<0.05) in the CFS model group. Following EA intervention, the
      grabbing force and the expression levels of ATP synthase mRNA, SIRT 1 and PGC-1
      alpha proteins and mRNAs, and p-AMPK/AMPK were significantly up-regulated in the
      EA-Zusanli (ST 36) group (P<0.05, P<0.01). CONCLUSION: EA of ST 36 can raise the
      grabbing force of CFS rats, which may be related to its effects in up-regulating
      the expression of ATP synthase mRNA, SIRT 1 and PGC-1 alpha proteins and mRNAs,
      and p-AMPK/AMPK to reduce mitochondrial oxidative stress reaction and in
      increasing ATP synthesis.

PMID- 30091538
TI  - [Electroacupuncture Combined with Intracerebral Injection of VEGF Improves
      Neurological Dysfunction Possibly by Down-regulating Expression of Endoplasmic
      Reticulum Stress Related Proteins ATF 6, etc. in Cerebral Ischemia-reperfusion
      Injury Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) and EA combined with
      intracerebral injection of vascular endothelial growth factor (VEGF) on
      endoplasmic reticulum stress (ERS) related proteins and genes as activating
      transcription factor (ATF 6), inositol requiring enzyme-1 (IRE 1), CCAAT/enhancer
      binding protein homologous protein (CHOP), X box-binding protein-1 (XBP 1) of
      cerebral ischemia reperfusion injury (CIRI) rats, so as to study its repair
      effect for CIRI. METHODS: Forty male SD rats were equally and randomly divided
      into 5 groups: sham operation, model, EA, VEGF and EA+VEGF groups (n=8). The CIRI
      model was established by occlusion of the middle cerebral artery (MCAO) with
      thread embolism method. For rats of the sham operation group, the right common
      carotid artery was isolated without MCAO. EA (2 Hz/100 Hz, 1-3 mA) was applied to
      "Baihui" (GV 20), left "Quchi" (LI 11) and left "Zusanli" (ST 36) for 30 min,
      once a day for 14 days. For rats of the VEGF and EA+VEGF groups, 10 uL VEGF
      (0.025 ug/uL) was injected into the lateral ventricle 24 h after successful
      modeling. The rats' neurological function was assessed by using the modified
      neurological severity score (mNSS), and the histopathological changes of cerebral
      tissue were observed by Nissl staining method. The expression levels of ERS
      related proteins and genes ATF 6, IRE 1, XBP 1 and CHOP were determined by
      western blot (WB) and fluorescent quantitative PCR, separately. RESULTS: After
      modeling, the level of mNSS was significantly higher in the model group than in
      the sham operation group (P<0.05), and the number of Nissl bodies was markedly
      lower in the model group than in the sham operation group (P<0.05). Following the
      treatment, the mNSS was significantly lower in the EA, VEGF and EA+VEGF groups
      than in the model group (P<0.05), and the numbers of Nissl bodies were obviously
      higher in the EA, VEGF and EA+VEGF groups than in the model group (P<0.05),
      suggesting an improvement of neurological dysfunction and a repair of the injured
      cerebral tissue after the treatment. The levels of CIRI-induced increase of mNSS
      and CIRI-induced decrease of the number of Nissl bodies in the EA+VEGF group were
      respectively remarkably lower or higher than those of the simple EA and simple
      VEGF groups (P<0.05). WB and PCR showed that the expression levels of ATF 6, IRE
      1, XBP1 and CHOP proteins and genes were notably higher in the model group than
      in the sham operation group (P<0.05), and considerably lower in the EA, VEGF and
      EA+VEGF groups than in the model group (P<0.05). Comparison among the three
      treatment groups showed that after the treatment, the expression levels of ATF 6,
      IRE 1, XBP1 and CHOP proteins and genes were obviously lower in the EA+VEGF group
      than in the EA and VEGF groups (P<0.05). CONCLUSION: EA and EA plus intracerebral
      microinjection of VEGF can improve neurological function and promote cerebral
      tissue repair in CIRI rats, which is associated with their effects in down
      regulating the expression of ERS related proteins ATF 6, IRE 1, XBP1 and CHOP.
      The effect of EA+VEGF is superior to that of simple EA and simple VEGF.

PMID- 30091539
TI  - [Effect of Catgut Implantation on Spatial Learning-memory Ability, Expression of
      Hippocampal Protein Kinase C Interacting Protein 1 and GluR 2 and Ca2+ Content in
      Rats with Chronic Ischemic Cognitive Impairment].
AB  - OBJECTIVE: To observe the effect of catgut embedment at "Baihui" (GV 20),
      "Dazhui" (GV 14), etc. on learning-memory ability, expression of hippocampal
      protein kinase C interacting protein 1 (PICK 1) and glutamate receptor 2 (GluR 2)
      proteins and level of calcium ions, so as to explore its mechanism underlying
      improvement of vascular cognitive impairment. METHODS: A total of 56 male SD rats
      were randomly divided into sham operation, model, catgut embedment and medication
      groups (n=14 in each). The chronic ischemic cognitive impairment model was
      established by permanent occlusion of bilate-ral common carotid arteries. The
      catgut embedment was applied to GV 20, GV 14, "Shenshu" (BL 23) and "Xuanzhong"
      (GB 39), once a week, for 4 weeks. Rats of the medication group received
      intraperitoneal injection of monosialate tetrahexose ganglioside sodium (GM-1,
      0.33 mg/kg), once daily for 4 weeks. The rats' learning-memory ability was
      detected by Morris water maze tasks, pathological changes of hippocampal Nissl's
      bodies were tested by Nissl staining. The expression levels of PICK 1 and GluR 2
      proteins in the hippocampus were detected by Western bolt (WB), and the
      concentration of calcium ions in the hippocampus tissue was measured by
      Bicinchoninic acid (BCA) assay. RESULTS: After modeling, the mean escape
      latencies of place navigation test were significantly increased while the
      crossing times of target platform quadrant of space probing test notably
      decreased in the model, catgut embedment and medication groups compared with
      their own individual pre-modeling (P<0.01). Following the treatment, the
      increased mean escape latencies and decreased crossing times were markedly
      reversed in both catgut embedment and medication groups relevant to the model
      group (P<0.01, P<0.05). Nissl staining showed that after mode-ling, a smaller
      amount of Nissl bodies with dispersing arrangement, reduction in cellular volume,
      and loss of large amount of cells with vague structure, and hyperchromatic
      nuclear pyknosis were found in the hippocampus tissue, which was relatively
      milder in both catgut embedment and medication groups. The hippocampal PICK 1
      protein expression and the calcium ion concentration were obviously higher in the
      model group than in the sham operation group (P<0.01), and significantly lower in
      both embedment and medication groups than in the model group (P<0.01, P<0.05),
      while hippocampal GluR 2 protein expression was obviously lower in the model
      group than in the sham operation group (P<0.01), and markedly higher in both
      embedment and medication groups than in the model group (P<0.05, P<0.01). No
      significant differences were found between the embedment and medication groups in
      the abovementioned indexes (P>0.05). CONCLUSION: Catgut implantation at GV 20
      etc. can effectively improve the learning-memory ability in rats with chronic
      ischemic cognitive impairment, which may be related to its effects in down
      regulating the expression of PICK 1 and calcium ion concentration and up
      regulating the expression of AMPA receptor subunit GluR 2 protein in the
      hippocampus.

PMID- 30091540
TI  - [Administration of Electroacupuncture and Da-Cheng-Qi Decoction Has a Synergetic
      Effect in Relieving Injury of Pancreas, Lung and Large Intestine and Inflammatory
      Reactions in Rats with Acute Pancreatitis].
AB  - OBJECTIVE: To explore the effectiveness of electroacupuncture (EA) stimulation of
      Shu-and Mu-points of Lung and Large Intestine Meridians combined with
      administration of Da-Cheng-Qi Decoction (DCQD) in the treatment of inflammatory
      injury in rats with acute pancreatitis, so as to reveal their synergetic anti
      inflammatory effect. METHODS: Forty male SD rats were randomly divided into five
      groups: normal control, model, DCQD, EA, EA+DCQD, with 8 rats in each group. All
      the rats except those in the normal group received a retrograde biliopancreatic
      duct injection of sodium Taurocholate (3.0%, 0.1 mL/100 g) to induce an acute
      pancreatitis model. Twenty-four hours after modeling, EA (4 Hz/50 Hz) was applied
      to bilateral Shu-points "Feishu" (BL 13) and "Dachangshu" (BL 25), and Mu-points
      "Zhongfu" (LU 1) and "Tianshu" (ST 25) for 20 min, once every 7 h, 3 times in
      total. Rats of the DCQD and EA+DCQD groups were given intra-gastric gavage of
      DCQD (1 mL/100 g) 24 h after modeling, and those of the other 3 groups were given
      intra-gastric gavage of same dosage of normal saline. The histopathological
      changes of the pancreas, lung and large intestine tissues were observed after H.
      E. staining and scored according to Schmidt's and colleagues' methods (the
      severity of edema, inflammation, hemorrhage, necrosis). The concentrations of
      interleukin-6 (IL-6) and IL-10 in the serum, and those of myeloperoxidase (MPO)
      and malonaldehyde (MDA) in the lung and large intestine tissues were detected by
      using double-antibody sandwich ELISA. RESULTS: After modeling, the
      histopathological scores of pancreas, lung and large intestine tissues, the
      concentrations of MPO and MDA in lung and large intestine, and the levels of IL-6
      and IL-10 in serum were significantly increased in the model group compared with
      the normal control group (P<0.05). Following the treatment, the histopathological
      scores of pancreas, lung and large intestine tissues, the contents of MPO and MDA
      in the lung and large intestine, and serum IL-6 were considerably reduced in the
      EA, DCQD and EA+DCQD groups relevant to the model group (P<0.05), while serum IL
      10 content was notably increased in the three treatment groups (P<0.05). The
      therapeutic effect of EA+DCQD was significantly superior to that of simple EA and
      simple DCQD in down-regulating the histopathological scores of lung and large
      intestine tissues, the contents of MPO and MDA in the lung and large intestine,
      and serum IL-6 level, and up-regulating serum IL-10 level (P<0.05). No
      significant differences were found between the EA and DCQD groups in the above
      mentioned 9 indexes (P>0.05). CONCLUSION: EA and DCQD can relieve the
      inflammatory injury of the pancreas, lung and large intestine tissues in rats
      with acute pancreatitis, and EA combined with DCQD has a better synergetic effect
      in reducing oxidative stress level and inflammatory reaction.

PMID- 30091542
TI  - [Effect of Electroacupuncture on Hippocampal IL-6, IL-1 beta, TNF-alpha and
      Norepinephrine Levels in Acute Myocardial Ischemia Rats].
AB  - OBJECTIVE: We have repeatedly demonstrated that electroacupuncture (EA)
      stimulation of "Shenmen" (HT 7)- "Tongli" (HT 5) segment of the Heart Meridian
      can improve acute myocardial ischemia (AMI). This study aimed at observing the
      effect of EA on contents of hippocampal norepinephrine (NE), and interleukin 6
      (IL-6), IL-1 beta and tumor necrosis factor- alpha (TNF-alpha) in AMI rats, so as
      to explore its underlying mechanism. METHODS: SD rats were randomly divided into
      3 groups: sham operation (sham), model and EA(n=6 rats in each). The anterior
      descending branch (ADB) of the left coronary artery was occluded to make an AMI
      model. For rats of the sham group, a surgical suture was simply threaded beneath
      the ADB without ligation. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral
      "Shenmen" (HT 7)- "Tongli" (HT 5) and the middle-point between HT 7 and HT 5 for
      30 min, once daily for 3 days. Electrocardiogram (ECG) of the neck-thoracic lead
      was recorded by using PowerLab 16. The contents of serum creatine kinase (CK),
      hippocampal IL-6, IL-1 beta and TNF-alpha were assayed by ELISA. The
      concentration of NE in hippocampal CA 1 area was detected by microdialysis
      combined with electrochemical detector. RESULTS: Compared with the sham group,
      the ECG-ST height, serum CK, hippocampal NE, IL-6, IL-1 beta and TNF-alpha
      contents of the CA 1 region were significantly increased in the model group
      (P<0.001). Whereas, after EA intervention, the serum CK, hippocampal NE, IL-6, IL
      1 beta and TNF-alpha contents were obviously down-regulated relevant to the model
      group (P<0.05, P<0.001), and the IL-6, IL-1 beta and TNF-alpha contents were
      positively correlated with the NE level (P<0.001, P<0.01). CONCLUSION: EA
      stimulation of the Heart Meridian may improve ischemic myocardial injury in AMI
      rats, probably by reducing the proinflammatory factors and hippocampal NE.

PMID- 30091541
TI  - [Manual Acupuncture Stimulation of Paired Acupoints Can Relieve Sleep Disorder
      Possibly by Upregulating Pineal Melatonin Protein and Its Receptor mRNA Levels in
      the Suprachiasmatic Nucleus in Insomnia Rats].
AB  - OBJECTIVE: To observe the effect of manual acupuncture stimulation of paired
      "Baihui" (GV 20)+ "Shenmen" (HT 7), GV 20+ "Sanyinjiao" (SP 6), and GV 20+ non
      acupoint on expression of melatonine (MT) and suprachiasmatic melatonin receptor
      1 (MT1) and melatonin receptor 2 (MT2) mRNAs in insomnia rats, so as to explore
      their action difference and the underlying mechanism in improving insomnia.
      METHODS: Male SD rats were randomly divided into normal control (n=12), mo-del
      (n=8), GV 20+HT 7(n=12), GV 20+SP 6(n=11), and GV 20+ non-acupoint (n=10) groups.
      The insomnia model was established by intraperitoneal injection of Para
      chlorophenylalanine suspension (50 mg/mL, 50 mg/100 g), once daily for 2 days.
      The abovementioned acupoints GV 20, bilateral HT 7, SP 6 and non-acupoints (the
      midpoint between the elbow-tip and armpit on the medial side of the upper-arm)
      were punctured with filiform needles and manipulated by rotating the needle for
      about 1 min which was repeated once again every 10 min during 30 minutes' needle
      retaining. The treatment was conducted once daily for 7 days. The expression
      levels of MT immunoactivity in the conarium tissue, and MT1 and MT2 mRNAs of the
      suprachiasmatic nucleus (SCN) region were detected using immunohistochemistry and
      fluorescence quantitative real time-PCR, respectively. RESULTS: After modeling,
      the expression levels of pineal MT (an increase of gray value means a decrease of
      immunoactivity), SCN MT1 and MT2 mRNAs were notably down-regulated in the model
      group relevant to the normal control group (P<0.05, P<0.01). Following the
      treatment, the down-regulated expression levels of MT protein, and MT1 and MT2
      mRNAs were obviously reversed in the GV 20 + HT 7, GV 20 + SP 6 groups relevant
      to the model group (P<0.05, P<0.01). The therapeutic effect of GV 20+ HT 7 was
      superior to that of GV 20+ non-acupoint in up-regulating the expression of MT1
      mRNA (P<0.01), and markedly superior to that of GV 20+ SP 6 and GV 20+ non
      acupoint in increasing the sleep duration and in up-regulating the expression of
      MT2 mRNA (P<0.01). No significant differences were found among the 3 treatment
      groups in up-regulating the expression of MT (P>0.05). CONCLUSION: Manual
      acupuncture stimulation of GV 20+ HT 7 and GV 20+ SP 6 can improve the sleep
      disorder in insomnia rats, which may be related to its effects in increasing the
      levels of pineal MT protein, and MT1 and MT2 mRNAs in hypothalamic SCN.

PMID- 30091543
TI  - [Effect of Electroacupuncture on Learning-memory Ability in Rats with Hypoxic
      ischemic Encephalopathy].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) on changes of
      learning-memory ability, psychomotor coordination and anxiety-like behavior of
      cerebral hypoxic-ischemia (CHI) young rats, so as to explore its protective
      effect on neurons under hypoxic-ischemic conditions. METHODS: SD rats (aged 7
      days) were randomly divided into sham operation (sham, n=12), model (n=11), and
      EA groups (n=12). In addition, 6 young rats in each group were used for observing
      the number of dendritic spines after Golgi staining. The CHI model was
      established by ligation of the left common carotid artery combined with hypoxia
      in a closed transparent vessel. EA was applied to "Baihui" (GV 20)and "Dazhui"
      (GV 14) for 20 min, once every other day, for 28 days. The rats' behavior changes
      were assessed by using rotarod performance (for psychomotor coordination),
      elevated plus maze (anxiety-like behavior) tests and Morris water maze (learning
      memory ability) tests, separately. RESULTS: After modeling, the average escape
      latency and average escape distance of location navigation test within 70 seconds
      were significantly increased (P<0.05), and the average times and average duration
      of safe-platform quadrant crossing of spacial probing test were markedly reduced
      relevant to the sham group (P<0.05). After EA treatment, CHI-induced increases of
      escape latency and escape distance, and the decreased times and duration of
      platform quadrant crossing were significantly reversed (P<0.05). No significant
      differences were found among the three groups in the falling latency of rotarod
      performance test, and in the time of opening and closing arms of elevated plus
      maze tests (P>0.05). The density of dendritic spines was significantly lo-wer in
      the model group than in the sham group (P <0.05), and notably higher in the EA
      group than in the model group (P<0.05). CONCLUSION: EA can improve the learning
      memory ability of CHI young rats, which may be related to its effect in
      protecting the dendritic spines of CA 1 region of hippocampus from injury.

PMID- 30091544
TI  - [Effect of Manual Acupuncture Preconditioning on Behavior and Contents of Serum
      CGRP, SP, IL-1 beta and TNF-alpha Levels in Migraine Rats].
AB  - OBJECTIVE: To observe the effect of liver-soothing and mental-activity-regulating
      (LSMAR) needling on behavior reactions and contents of serum calcitonin gene
      related peptide (CGRP), substance P (SP), interleukin-1 beta (IL-1 beta) and
      tumor necrosis factor-alpha (TNF-alpha) in migraine rats, so as to explore its
      mechanism underlying relief of migraine. METHODS: Thirty-two male Wistar rats
      were randomly divided into control, model, LSMAR needling and conventional
      needling groups (n=8 rats in each). The migraine model was established by
      hypodermic injection of glyceryl trinitrate (5 mg/kg) at the napex. Acupuncture
      preconditioning was conducted once daily for 8 days before modeling. Acupuncture
      needles were inserted into "Baihui" (GV 20), and bilateral "Fengchi" (GB 20),
      "Neiguan" (PC 6) and "Taichong" (LR 3), manipulated for a while and retained for
      30 min. The rats' behavioral changes (times of head scratching, tail-biting, cage
      crawling, and to- and fro-movement in 30 min) were scored (one symptom = one
      point) before modeling, after modeling, and after intervention. The
      concentrations of CGRP, SP, IL-1 beta, TNF-alpha in serum were assayed by enzyme
      linked immunosorbent assay (ELISA). RESULTS: After modeling, the behavioral
      scores were significantly increased in the migraine model rats relevant to the
      control group (P<0.05). Whereas after the treatment, the behavior scores were
      considerably decreased during 60-90 min and 120-150 min of the measuring period
      in both LSMAR and conventional needling groups compared with the model group
      (P<0.05). The concentrations of CGRP, SP, IL-1 beta and TNF-alpha were
      significantly higher in the model group than in the control group (P<0.05), and
      notably lower in both LSMAR and conventional needling groups than in the model
      group (P<0.05). The therapeutic effect of LSMAR was markedly superior to that of
      conventional needling in down-regulating the concentrations of CGRP, SP, IL-1
      beta and TNF-alpha (P<0.05). CONCLUSION: Acupuncture preconditioning can
      effectively relieve pain in migraine rats possibly by decreasing the
      concentrations of CGRP, SP, IL-1 beta and TNF-alpha in the peripheral blood, and
      the therapeutic effect of LSMAR is evidently superior to that of conventional
      needling.

PMID- 30091545
TI  - [Treatment of Stroke Patients with Shoulder-wrist Syndrome by Acupoint Catgut
      Embedding and Surface Electromyogram Biofeedback Therapy].
AB  - OBJECTIVE: To observe the clinical effectiveness of acupoint catgut embedding and
      surface electromyogram biofeedback therapy (sEMGBF) in the treatment of stroke
      patients complicated with shoulder-hand syndrome (SHS). METHODS: A total of 90
      stroke patients with SHS were randomly divided into acupoint catgut embedment
      (ACE), sEMGBF and ACE+sEMGBF (combined treatment) groups (n=30 cases/group). The
      catgut embedment was performed at Jianliao (LI 14), Jianyu (LI 15), Quchi (LI
      11), Waiguan (TE 5) on the affected side, once every 3 weeks, twice altogether.
      The electromyographic biofeedback therapy (30-50 Hz, pulse duration 200 us, 6 s
      on and 10 s-off, appropriate strength) was applied to the skin area co-vering the
      deltoid muscle, flexor muscle of wrist and wrist extensor for 20 min, once per
      day, 5 times/week, for 6 weeks. The total effective rate was assessed by using
      Liao's and Zhu's methods (1996), the pain severity assessed using visual analogue
      scale (VAS), and Fugl-Meyer assessment (FMA, 66-points) scale and the patients'
      activities of daily living function (ADL, 100-points) were also scored. RESULTS:
      Before treatment, the VAS, FMA and ADL points of the three groups were not
      significantly different (P>0.05). After the treatment, the total effective rate
      (93.33%), FMA and ADL scores of the combined treatment group were significantly
      higher than those of the ACE and sEMGBF groups (P<0.05), while the VAS score of
      the combined treatment group was significantly lower than those of the ACE and
      sEMGBF groups (P<0.05). The total effective rates, FMA and ADL scores of the ACE
      and sEMGBF groups were comparable (P>0.05). The VAS score of the ACE group was
      markedly lower than that of the sEMGBF group (P<0.05). CONCLUSION: The combined
      administration of ACE and sEMGBF has a better therapeutic effect for stroke
      patients complicated with SHS relevant to simple ACE and simple sEMGBF therapy in
      improving the upper limb function, relieving pain, and enhancing the daily life
      quality.

PMID- 30091546
TI  - [Biological Ultra-weak Luminescence and Its Application to Research of
      Acupuncture].
AB  - Ultra-weak bioluminescence (UWL) is a physiological phenomenon widely existing in
      all the biological activities including human, animals, plants, etc., which
      reflects the energy metabolism of the organism. Since the last century, ultra
      weak photon emission (UPE) has been applied to the study of the essence of
      meridians and acupoints of traditional Chinese medicine and obtained some results
      as the higher luminescence characteristics, but many problems remain unsolved due
      to the limitation of detection technology. In recent years, along with the
      development of bioluminescence signal acquiring system and imaging system, we are
      able to further explore the characteristics and biological mechanisms of UWL of
      acupuncture points and meridians in the human body. We proposed to study changes
      of ultra-weak luminous intensity of acupuncture points and meridians before and
      after needling stimulation, and the delayed effect of UPE phenomenon, etc.,
      trying to reveal their regularities and essence. In this paper, the prospect of
      application of UPE to acupuncture research is also discussed by combining newly
      acquired results of some biological substances of acupoints in experimental
      studies.

PMID- 30091547
TI  - [Analysis of Regularity of Acupoint Selection in Acupuncture Treatment of
      Urticaria Based on Data Mining Technology].
AB  - OBJECTIVE: To analyze the regularity of acupoint selection, main acupoints and
      theoretical basis in acupuncture treatment of urticaria. METHODS: Papers
      collected from the time of establishment of each database to September of 2017
      were retrieved from databases CNKI, CBM, VIP and WF by using keywords of
      "acupuncture" "moxibustion" "blood-letting therapy" "autohemotherapy" "cupping"
      "acupoint catgut embedding" "auricular points" "acupoint injection" "fire-needle"
      (or red-hot needle), "dermal needle" "needle-embedding" "urticaria" in both
      Chinese and English. The collected papers were brought into analysis according to
      the inclusion and exclusion criteria, from which the prescriptions for
      acupuncture treatment of urticaria were subjected into descriptive statistical
      analysis, association rule analysis, and cluster analysis by using Access 2010,
      Clementine 18.0 and Stata software. RESULTS: Outcomes of analysis indicated that
      the treatment methods of urticaria with acupuncture and moxibustion, with
      different emphases, may be classified into eight categories. For treating the
      exterior syndrome of urticaria, acupoints of the Bladder Meridian, Governor
      Vessel and Conception Vessel were often employed to harmonize Ying and Wei and to
      dispel the pathogenic wind, while for treating the interior syndrome, acupoints
      of the Large Intestine Meridian, Spleen Meridian, and Stomach Meridian were
      usually used to invigorate the spleen to dispel dampness and to regulate blood
      circulation. The top five frequently used acupoints were Quchi (LI 11), Xuehai
      (SP 10), Zusanli (ST 36), Sanyinjiao (SP 6) and Geshu (BL 17). It was crucial to
      make use of the specific acupoints with adequate meridian-qi, such as He-Sea
      points, Back-Shu points, and Yuan-Primary points. There were some fixed forms in
      the combination of acupoints, including LI 11, SP 10, Dazhui (GV 14) and
      auricular Lung, Shenmen, Fengxi, Adrenal gland, which had the highest confidence
      coefficient for the meridian points and ear acu-points, respectively. The
      outcomes of cluster analysis about the acupoint prescriptions showed that 12
      acupoint groups as the SP 6-Hegu (LI 4)-LI 11-SP 10-ST 36, etc. were frequently
      used. CONCLUSION: The regularity of acupuncture treatment of urticaria can be
      discovered using data mining technology, resulting in an in-depth understanding
      and having a solid theoretical basis.

PMID- 30091548
TI  - [Evolvement of Acupuncture Needle Manipulation Techniques Described in Textbooks
      of Acupuncture and Moxibustion of Successive Editions].
AB  - This paper summarizes the evolvement of the needle manipulation techniques
      described in the textbooks of Acupuncture and Moxibustion of the past successive
      10 editions in Chinese, analyzes the reasons for the evolvement and its impact on
      clinical treatment, and proposes future developing trends. After analyzing
      characteristics of needle-manipulation techniques of the well-known Chinese
      acupuncture specialists, and those described in multi-editions of the textbooks,
      we found that the currently evoluted contents primarily contain the definition
      and types of manipulating techniques. However, the reasons for the evolvement and
      connotation of needle manipulating are probably due to a) undefined descriptions
      in the history; b) changes in the academic studies and clinical application of
      acupuncture and moxibustion during the textbook compilation; c) the well-known
      specialists' and the participated editors' academic thoughts; d) the textbook
      content setting needs, etc. The evolvement reflects the changed preoccupations of
      factors affecting clinical efficacy of acupuncture manipulations, and facilitates
      the implementation of standardized clinical operative procedures. The development
      of current acupuncture needle manipulation techniques emphasizes the
      quantification of manual manipulations, fits clinical needs, and pays more
      attention to the pressing hand during needle insertion.

PMID- 30091549
TI  - Lyme disease: recognition and management for emergency nurses.
AB  - Over the past ten years there has been a significant rise in the number of people
      who present to emergency departments with Lyme disease. Although some patients
      remain asymptomatic many present with a rash around a previous tick bite and
      others may present with a range of debilitating symptoms that can be problematic
      if left untreated. Due to the growing prevalence of Lyme disease in the UK and
      the US this article gives an overview of the vector-borne condition and provides
      emergency nurses with information about the pathophysiology, prevention,
      presenting signs and symptoms and management.

PMID- 30091550
TI  - [Combined Influence of Arisaematis Rhizoma Polysaccharide with Cisplatin on the
      Proliferation,Apoptosis and Epithelial Mesenchymal Transition of Breast Carcinoma
      MDA-MB-231 Cells].
AB  - Objective: To explore the combined influence of Arisaematis Rhizoma
      polysaccharide with cisplatin on the proliferation,apoptosis and epithelial
      mesenchymal transition of breast carcinoma MDA-MB-231 cells. Methods: MDA-MB-231
      cells were divided into control group,Arisaematis Rhizoma polysaccharide group(
      50 MUg / m L),cisplatin group( 5 MUg / m L) and combined group( Arisaematis
      Rhizoma polysaccharide + cisplatin); the cells proliferation were detected by MTT
      assay, the cells apoptosis were detected by Annexin V / PI flow cytometry, the
      mRNA expression levels of Vimentin, N-cadherinand E-cadherin were detected by
      Real time PCR, the levels of Fibronectin( FN) were detected by ELISA,and the
      levels of Akt and p-Akt were measured by western blotting. Results: The
      proliferation of MDA-MB-231 cells were inhibited in Arisaematis Rhizoma
      polysaccharide group, cisplatin group and combined group with a time dependent
      manner. The early, late apoptosis rate and E-cadherin mRNA level in Arisaematis
      Rhizoma polysaccharide group, cisplatin group and combined group were
      higher,while Vimentin,N-cadherin mRNA,FN level and p-Akt / Akt were lower than
      those in control group( P < 0. 05). Compared with Arisaematis Rhizoma
      polysaccharide group and cisplatin group, there were higher in the early,late
      apoptosis rate and E-cadherin mRNA levels, lower the mRNA levels of Vimentin, N
      cadherin, FN and p-Akt / Akt in combined group( P <0. 05). Conclusion: Both of
      Arisaematis Rhizoma polysaccharide and cisplatin can affect the proliferation,
      apoptosis and epithelial-mesenchymal transition, and inhibit activation of PI3 K
      / Akt signaling pathway and the combined effect is better.

PMID- 30091551
TI  - Medicare Program; Prospective Payment System and Consolidated Billing for Skilled
      Nursing Facilities (SNF) Final Rule for FY 2019, SNF Value-Based Purchasing
      Program, and SNF Quality Reporting Program. Final rule.
AB  - This final rule updates the payment rates used under the prospective payment
      system (PPS) for skilled nursing facilities (SNFs) for fiscal year (FY) 2019.
      This final rule also replaces the existing case-mix classification methodology,
      the Resource Utilization Groups, Version IV (RUG-IV) model, with a revised case
      mix methodology called the Patient- Driven Payment Model (PDPM) beginning on
      October 1, 2019. The rule finalizes revisions to the regulation text that
      describes a beneficiary's SNF "resident" status under the consolidated billing
      provision and the required content of the SNF level of care certification. The
      rule also finalizes updates to the SNF Quality Reporting Program (QRP) and the
      Skilled Nursing Facility Value-Based Purchasing (VBP) Program.

PMID- 30091552
TI  - [Estrogenic Activities of Alcohol Extract from Phellinus lonicerinus].
AB  - Objective: To investigate the estrogenic activities of alcohol extract from
      Phellinus lonicerinus( AEPL). Methods: Estrogen and anti-estrogen effects were
      evaluated by cell proliferation experiment in vitro. Through elevating young rat
      uterine weight, castrated female rats, and adult female rats uterus index serum
      estradiol( E2) and progesterone( P) were analyzed by enzyme immune methods, and
      uterine estrogen receptor alpha( ERalpha) and estrogen receptor beta( ERbeta)
      protein expressions were measeured by immunohistochemisty, and investigated the
      histopathological of uterus, ovary, and breast of adult female rats. Results:
      Compared with the control group, AEPL promoted estrogen-sensitive MCF-7
      proliferation significantly( P < 0. 05 or P < 0. 01) in the doses of 5 ~ 50 MUg /
      m L in vitro experiment; compared with the E2 control group, it also presented
      anti-estrogenic effect in E2-induced MCF-7 cells at the doses of 10 ~ 100 MUg / m
      L( P < 0. 05 or P < 0. 01). In the animal experiments, AEPL remarkably increased
      serum E2 content and promoted growth of uterus in primary female mice at the dose
      of 300 mg / kg; and raised the serum E2 and P content, alleviated uterine atrophy
      caused by estrogen deficiency in castrated rats at the dose of 240 mg / kg. In
      adult female rats, AEPL markedly increased the serum P content at the dose of 120
      mg / kg, and also markedly increased the serum E2 content at the dose of 120,240
      mg / kg, and regulated the protein expressions of ERalphaand ERbeta. AEPL has no
      effects on histopathological changes of uterus, ovary and mammary gland in rats.
      Conclusion: AEPL shows estrogenic effects with fewer adverse reaction, which
      possesses the replacement of estrogen application prospects.

PMID- 30091553
TI  - The Welfare Cost of Perceived Policy Uncertainty: Evidence from Social Security.
AB  - Policy uncertainty reduces individual welfare when individuals have limited
      opportunities to mitigate or insure against the resulting consumption
      fluctuations. We field an original survey to measure the degree of perceived
      policy uncertainty in Social Security benefits and to estimate the impact of this
      uncertainty on individual welfare. Our central estimates show that on average
      individuals are willing to forgo 6 percent of the benefits they are supposed to
      get under current law to remove the policy uncertainty associated with their
      future Social Security benefits. This translates to a risk premium from policy
      uncertainty equal to 10 percent of expected benefits.

PMID- 30091555
TI  - Making the Best of Tech Funding.

PMID- 30091554
TI  - The Seacole statue comes at just the right moment.
AB  - In the wake of Brexit, a tribute to the pioneering black nurse should offer
      inspiration in the battles against racism.

PMID- 30091556
TI  - Thoughts on the Post-Brexit Landscape.

PMID- 30091557
TI  - Making the Most From the Money.
AB  - How to reduce unwarranted variation in the NHS was the focus of debate among
      experts brought together for HSJ's latest roundtable, as Alison Moore reports.

PMID- 30091559
TI  - The message on accessibility is getting through.
AB  - Steps are finally being taken to bring down barriers to understanding what
      accessible information is and how it can transform lives, as Dr. Clare Mander
      explains.

PMID- 30091558
TI  - How to tackle the dearth of nurses.
AB  - Ben Morrin and Flo Panel-Coates analyse the cause and effect of nurse shortage
      plaguing the city of London.

PMID- 30091560
TI  - The Economic Consequences of Hospital Admissions.
AB  - We use an event study approach to examine the economic consequences of hospital
      admissions for adults in two datasets: survey data from the Health and Retirement
      Study, and hospitalization data linked to credit reports. For non-elderly adults
      with health insurance, hospital admissions increase out-of-pocket medical
      spending, unpaid medical bills, and bankruptcy, and reduce earnings, income,
      access to credit, and consumer borrowing. The earnings decline is substantial
      compared to the out-of-pocket spending increase, and is minimally insured prior
      to age-eligibility for Social Security Retirement Income. Relative to the insured
      non-elderly, the uninsured non-elderly experience much larger increases in unpaid
      medical bills and bankruptcy rates following a hospital admission. Hospital
      admissions trigger fewer than 5 percent of all bankruptcies in our sample.

PMID- 30091561
TI  - Hunt's good intentions fall foul of the immigration dog whistle.
AB  - Attempts to discuss the expansion of medical training crashed into skepticism of
      how this could happen post-Brexit.

PMID- 30091562
TI  - Rise of the connected patient.
AB  - Smart analytics can play a significant role in healthcare of the future - so how
      do we make them work, asks John Loder.

PMID- 30091563
TI  - Advertising and Risk Selection in Health Insurance Markets.
AB  - This paper studies the impact of advertising as a channel for risk selection in
      Medicare Advantage. We provide evidence that insurer advertising is responsive to
      the gains from risk selection. Then we develop and estimate an equilibrium model
      of Medicare Advantage with advertising, allowing rich individual heterogeneity.
      Our estimates show that advertising is effective in attracting healthy
      individuals who are newly eligible for Medicare, contributing to advantageous
      selection into Medicare Advantage. Moreover, risk selection through advertising
      substantially lowers premiums byimproving insurers' risk pools. The
      distributional implication is that unhealthy consumers may be better off through
      cross-subsidization from healthy individuals.

PMID- 30091564
TI  - Elephant trap alert: STPs must stay the right side of the law.
AB  - We must design sustainability and transformation plans well if their good work is
      not to be derailed by legal challenges.

PMID- 30091565
TI  - What's Trump got to do with our healthcare system? Plenty.
AB  - The election reminds us that rising demand and falling revenues can't continue -
      and that we must take personal responsibility.

PMID- 30091566
TI  - In search of a stop to same day cancellation.
AB  - A northern trust created a role to identify the causes of same day cancellations 
      and possible methods for reducing them.

PMID- 30091567
TI  - Why Good Healing Is A Good Business.
AB  - Wound infections can dramatically lengthen treatment times and cost the NHS large
      sums of money, which is why funding for preventative measures is so important,
      writes Claire Read.

PMID- 30091568
TI  - It's time to bring the hidden half million out of the shadows.

PMID- 30091569
TI  - Family Ruptures, Stress, and the Mental Health of the Next Generation.
AB  - This paper studies how in utero exposure to maternal stress from family ruptures
      affects later mental health. We find that prenatal exposure to the death of a
      maternal relative increases take-up of ADHD medications during childhood and anti
      anxiety and depression medications in adulthood. Further, family ruptures during
      pregnancy depress birth outcomes and raise the risk of perinatal complications
      necessitating hospitalization. Our results suggest large welfare gains from
      preventing fetal stress from family ruptures and possibly from economically
      induced stressors such as unemployment. They further suggest that greater stress
      exposure among the poor may partially explain the intergenerational persistence
      of poverty.

PMID- 30091570
TI  - The three skills needed to be an effective NHS chief executive.
AB  - Some lessons from serving as UCLH foundation trust's chief executive for 16 years
      - and the next chapter of my career.

PMID- 30091571
TI  - How to bring the NHS back from the permanent brink of collapse.
AB  - Three sets of coordinated actions are required if the health service is to pull
      back from the edge of the cliff - and stay there.

PMID- 30091572
TI  - Ripping up the Rules on Records.
AB  - Estonia's health record system is a fast-paced success story that began in part
      when a reorganization left GPs without access to patient information, as Claire
      Read explains.

PMID- 30091574
TI  - The public need more truths and fewer glossy documents.
AB  - It's time for health chiefs to engage with skeptical citizens if sustainability
      and transformation plans are to succeed.

PMID- 30091573
TI  - Legal Origins and Female HIV.
AB  - More than one-half of all people living with HIV are women and 80 percent of all
      HIV-positive women in the world live in sub- Saharan Africa. This paper
      demonstrates that the legal origins of these formerly colonized countries
      significantly determine current-day female HIV rates. In particular, female HIV
      rates are significantly higher in common law sub- Saharan African countries
      compared to civil law ones. This paper explains this relationship by focusing on
      differences in female property rights under the two codes of law. In sub- Saharan
      Africa, common law is associated with weaker female marital property laws. As a
      result, women in these common law countries have lower bargaining power within
      the household and are less able to negotiate safe sex practices and are thus more
      vulnerable to HIV, compared to their civil law counterparts. Exploiting the fact
      that some ethnic groups in sub- Saharan Africa cross country borders with
      different legal systems, we are able to include ethnicity fixed effects into a
      regression discontinuity approach. This allows us to control for a large set of
      cultural, geographical, and environmental factors that could be confounding the
      estimates. The results of this paper are consistent with gender inequality (the
      "feminization" of AIDS), explaining much of its prevalence in sub- Saharan
      Africa.

PMID- 30091575
TI  - How to Go Digital and Influence People.
AB  - Leaders at some of the NHS global digital exemplar trusts tell Claire Read how
      stability of leadership and consistency of direction have been key factors in
      their success.

PMID- 30091576
TI  - Is the NHS Winning the Great Paper Chase?
AB  - A paper-free health service is a worthy ambition but achieving it has proved
      easier said than done - so what might a more realistic plan look like, asks
      Matthew Shelley.

PMID- 30091577
TI  - Escaping Malthus: Economic Growth and Fertility Change in the Developing World.
AB  - Following mid-twentieth century predictions of Malthusian catastrophe, fertility
      in the developing world more than halved, while living standards more than
      doubled. We analyze how fertility change related to economic growth during this
      episode, using data on 2.3 million women from 255 household surveys. We find
      different responses to fluctuations and long-run growth, both heterogeneous over
      the life cycle. Fertility was procyclical but declined and delayed with long-run
      growth; fluctuations late (but not early) in the reproductive period affected
      lifetime fertility. The results are consistent with models of the escape from the
      Malthusian trap, extended with a life cycle and liquidity constraints.

PMID- 30091578
TI  - Correction to "Supramolecular Chemotherapy: Carboxylated Pillar[6]arene for
      Decreasing Cytotoxicity of Oxaliplatin to Normal Cells and Improving Its
      Anticancer Bioactivity Against Colorectal Cancer".

PMID- 30091580
TI  - Direct Reprogramming of Glioblastoma Cells into Neurons Using Small Molecules.
AB  - Glioblastoma multiforme, a type of deadly brain cancer, originates most commonly
      from astrocytes found in the brain. Current multimodal treatments for
      glioblastoma minimally increase life expectancy, but significant advancements in
      prognosis have not been made in the past few decades. Here we investigate
      cellular reprogramming for inhibiting the aggressive proliferation of
      glioblastoma cells. Cellular reprogramming converts one differentiated cell type
      into another type based on the principles of regenerative medicine. In this
      study, we used cellular reprogramming to investigate whether small molecule
      mediated reprogramming could convert glioblastoma cells into neurons. We
      investigated a novel method for reprogramming U87MG human glioblastoma cells into
      terminally differentiated neurons using a small molecule cocktail consisting of
      forskolin, ISX9, CHIR99021 I-BET 151, and DAPT. Treating U87MG glioblastoma cells
      with this cocktail successfully reprogrammed the malignant cells into early
      neurons over 13 days. The reprogrammed cells displayed morphological and
      immunofluorescent characteristics associated with neuronal phenotypes. Genetic
      analysis revealed that the chemical cocktail upregulates the Ngn2, Ascl1, Brn2,
      and MAP2 genes, resulting in neuronal reprogramming. Furthermore, these cells
      displayed decreased viability and lacked the ability to form high numbers of
      tumor-like spheroids. Overall, this study validates the use of a novel small
      molecule cocktail for reprogramming glioblastoma into nonproliferating neurons.

PMID- 30091579
TI  - Interface Engineering of Gold Nanoclusters for CO Oxidation Catalysis.
AB  - Catalysts based on atomically precise gold nanoclusters serve as an ideal model
      to relate the catalytic activity to the geometrical and electronic structures as
      well as the ligand effect. Herein, we investigate three series of ligand
      (thiolate)-protected gold nanoclusters, including Au38(SR)24, Au36(SR')24, and
      Au25(SR")18, with a focus on their interface effects using carbon monoxide (CO)
      oxidation as a probe reaction. The first comparison is within each series, which
      reveals the same trend for the three series that, rather than the bulkiness of
      carbon tails as commonly thought, the steric hindrance of ligands at the
      interface between the thiolate, Au, and CeO2 inhibits CO adsorption onto Au sites
      and hence adversely affects the activity of CO oxidation. The second comparison
      is between the sets Au38(SR)24 and Au36(SR')24 of nearly the same size, which
      reveals that the Au36(SR')24 nanoclusters (with face centered cubic structure)
      are not sensitive to thermal pretreatment conditions, whereas the Au38(SR)24
      catalysts (icosahedral structure) are and an optimum activity is observed at a
      pretreatment temperature of 150  degrees C. Overall, the atomically precise Au
      n(SR) m nanoclusters have revealed unprecedented details on the catalytic
      interface and atomic structure effects. It is hoped that such insights will
      benefit the ultimate goal of catalysis in future design of enzymelike catalysts
      for environmentally friendly green catalysis.

PMID- 30091581
TI  - Photovoltaic Field-Effect Transistors Using a MoS2 and Organic Rubrene van der
      Waals Hybrid.
AB  - A several-layer n-type MoS2 was partially hybridized with an organic crystalline
      p-type rubrene nanosheet through van der Waals interactions to fabricate a two
      dimensional (2-D) lateral-type n-p heterojunction optoelectronic device. The
      field-effect transistors (FETs) using lateral-type MoS2/rubrene hybrids exhibited
      both gate-tunable diode and anti-ambipolar transistor characteristics. The FET
      devices show the coexistence of n-type states, p-type states, and off-states
      controlled by the gate bias. From the photocurrent mapping experiments, the gate
      bias-dependent photovoltaic effect was observed from the heterojunction regions
      of the MoS2/rubrene FETs. Furthermore, the photovoltaic FETs were successfully
      operated by light irradiation without applying source-drain bias and controlled
      using gate bias. These devices represent new solar-energy-driven 2-D
      multifunctional electronic devices.

PMID- 30091582
TI  - Conductive Polymer Protonated Nanocellulose Aerogels for Tunable and Linearly
      Responsive Strain Sensors.
AB  - Strong and highly conductive aerogels have been assembled from cellulose
      nanofibrils (CNFs) protonated with conductive poly(3,4-ethylene
      dioxythiophene)/poly(styrene sulfonate) (PEDOT/PSS) complex at equal mass or
      less. Protonating CNF surface carboxylates and hydrogen-bonding CNF surface
      carboxyls with PSS in PEDOT/PSS generated PEDOT/PSS/CNF aerogels that were up to
      ten times stronger while as conductive as neat PEDOT/PSS aerogel, attributed to
      the transformation of PEDOT benzoid structure to the more electron transfer
      preferred quinoid structure. Ethylene glycol vapor annealing further increased
      the conductivity of PEDOT/PSS/CNF aerogels by 2 orders of magnitude. The
      poly(dimethylsiloxane) (PDMS)-infused conductive PEDOT/PSS/CNF aerogel (70 wt %
      CNF) transform a resistance-insensitive PDMS-infused PEDOT/PSS aerogel (gauge
      factor of 1.1 * 10-4) into a stretchable, sensitive, and linearly responsive
      strain sensor (gauge factor of 14.8 at 95% strain).

PMID- 30091583
TI  - Luminescent Hybrid Membrane-Based Logic Device: From Enantioselective
      Discrimination to Read-Only Memory for Information Processing.
AB  - Logic circuit device and molecular computer are idealized binary tools that
      implement manifold signal transformation and operation and is a basic component
      of integrated circuits and is widely used in computer, computerized numerical
      control, and communication fields. By combining the advantages of synthetic
      feasibility and enantioselective luminescent recognition, a logic device based on
      the lanthanide functional membrane has been constructed to effectively recognize
      the enantiomer and judge the enantiomer excess of the chair drug mixture. In
      addition, it would be interesting if such a logic circuit could be assembled into
      a loop circuit to realize intelligent control of the electronic component. Read
      only memory arrays built by the logic circuit are also actualized, which can be
      converted and stored in binary strings. This work provides an active and
      universal approach to modulate a luminescent device and logic circuit based on a
      chemical sensor, with promising application for intelligent control, information
      processing, and human-machine interaction.

PMID- 30091584
TI  - Hydrogel-Based Bioprocess for Scalable Manufacturing of Human Pluripotent Stem
      Cell-Derived Neural Stem Cells.
AB  - Neural stem cells derived from human pluripotent stem cells (hPSC-NSCs) are of
      great value for modeling diseases, developing drugs, and treating neurological
      disorders. However, manufacturing high-quantity and -quality hPSC-NSCs,
      especially for clinical applications, remains a challenge. Here, we report a
      chemically defined, high-yield, and scalable bioprocess for manufacturing hPSC
      NSCs. hPSCs are expanded and differentiated into NSCs in microscale tubes made
      with alginate hydrogels. The tubes are used to isolate cells from the
      hydrodynamic stresses in the culture vessel and limit the radial diameter of the
      cell mass to less than 400 MUm to ensure efficient mass transport during the
      culture. The hydrogel tubes provide uniform, reproducible, and cell-friendly
      microspaces and microenvironments for cells. With this new technology, we showed
      that hPSC-NSCs could be produced in 12 days with high viability (~95%), high
      purity (>90%), and high yield (~5 * 108 cells/mL of microspace). The volumetric
      yield is about 250 times more than the current state-of-the-art. Whole
      transcriptome analysis and quantitative real-time polymerase chain reaction
      showed that hPSC-NSCs made by this process had a similar gene expression to hPSC
      NSCs made by the conventional culture technology. The produced hPSC-NSCs could
      mature into both neurons and glial cells in vitro and in vivo. The process
      developed in this paper can be used to produce large numbers of hPSC-NSCs for
      various biomedical applications in the future.

PMID- 30091585
TI  - Introducing Artificial Solid Electrolyte Interphase onto the Anode of Aqueous
      Lithium Energy Storage Systems.
AB  - Aqueous lithium energy storage systems (ALESSs) offer several advantages over the
      commercially available nonaqueous systems, and the most noteworthy is that ALESSs
      have higher ionic conductivity, can be used safely, and are environmental
      friendly in nature. The ALESS, however, exhibits faster capacity fading than
      their nonaqueous counterparts after repeated cycles of charge and discharge, thus
      limiting their wide-range applications. Excessive corrosion of metallic anodes in
      the aqueous electrolyte and accelerated growth of dendrites during the charge
      discharge process are found to be the main reasons that severely impact the life
      span of ALESSs. Here, we introduce ultrathin graphene films as an artificial
      solid electrolyte interface (G-SEI) on the surface of a zinc anode to improve the
      cycling stability of an aqueous lithium battery system. The G-SEI is fabricated
      at different thicknesses and areas ranging from ~1 to 100 nm and ~1 to 10 cm2,
      respectively, via a Langmuir-Blodgett trough method and deposited onto the
      surface of the zinc anode. Electrochemical characterizations show a significant
      reduction in corrosion current density (0.033 mA cm-2 vs 1.046 mA cm-2 for the
      control), suppression of dendritic growth (~50%), and reduction in charge
      transfer resistance (222 Omega vs 563 Omega for the control) when the G-SEI is
      utilized. The aqueous battery system with the G-SEI (100 nm thickness) on the
      anode exhibits ~17% improvement in cycling stability (82% capacity retention
      after 300 cycles) compared to the control system. Comprehensive microscopy and
      spectroscopy characterizations reveal that the G-SEI not only controls the ion
      transport between the electrolyte and the anode surface (lower corrosion) but
      also promotes a uniform deposition (less dendritic growth) of zinc on the anode.

PMID- 30091586
TI  - Controlled Synthesis of Sulfur-Rich Polymeric Selenium Sulfides as Promising
      Electrode Materials for Long-Life, High-Rate Lithium Metal Batteries.
AB  - High-energy lithium/sulfur (Li/S) batteries still suffer from unsatisfactory
      cycle life and poor rate capability caused by the polysulfides shuttle and
      insulating nature of S cathodes. Here, we report our findings in the controlled
      synthesis of selenium (Se)-containing S-rich co-polymers of various compositions
      as novel cathode materials through a facile inverse vulcanization of S with
      selenium disulfide (SeS2) and 1,3-diisopropenylbenzene (DIB) as co-monomers.
      Nuclear magnetic resonance and X-ray photoelectron spectroscopy results show that
      divinyl functional groups of DIB were chemically cross-linked with S/SeS2 chain
      radicals through a ring-opening polymerization. The newly formed bonds of C-S, C
      Se, and S-Se in novel S-SeS2-DIB co-polymers effectively alleviate the shuttle
      effects of polysulfides/polyselenides. Furthermore, various electrochemical
      techniques confirm the positive roles of Se-containing co-polymers in enhancing
      the electrode reaction kinetics and the formation of stable solid electrolyte
      interphase layer with low charge-transfer resistance, leading to improved high
      rate performances. The as-synthesized co-polymer was then infiltrated into well
      interconnected, porous nanocarbon networks (Ketjenblack EC600JD, KB600) to
      provide effective paths for the fast electron transport. Due to the synergistic
      combination of chemical and physical confinement of the reaction intermediates
      during cycling, good reversibility for 500 cycles with a low decay rate of
      0.0549% per cycle was achieved at 1000 mA g-1. These encouraging results suggest
      that the combination of chemical incorporation of SeS2 into S-rich co-polymer and
      the physical confinement of carbon networks is a promising strategy for advancing
      Li/S batteries and their viability for practical applications.

PMID- 30091587
TI  - Understanding the Mechanism for Capacity Decay of V6O13-Based Lithium-Metal
      Polymer Batteries.
AB  - Capacity decay has been a well-known phenomenon in battery technology. V6O13 has
      been proved to be one of promising cathode materials for the lithium-metal
      polymer battery owing to high electrochemical capacity and electronic
      conductivity. However, these V6O13-based cathodes suffer from characteristic
      capacity decline under operating conditions, and it is also difficult to achieve
      the theoretical capacities of V6O13. Herein, we report, for the first time, the
      thermal instability between the components in the cathode composites using
      various analytical methods, such as in situ thermal gravimetric analysis:
      infrared spectroscopy, scanning electron microscopy, and X-ray diffraction
      techniques. This thermal instability is believed to be a chemical reaction
      between the binding material (polyalkylene glycols) and V6O13, which enables an
      improved understanding of the decay in the capacity of V6O13-based cathodes and
      initial capacities that are significantly below the theoretical value. The
      identification of the reaction between cathode and binding materials may trigger
      the further investigation of capacity decay of other cathode materials, paving
      the way to the design and development of high-capacity batteries.

PMID- 30091588
TI  - Fourier Transform-Ion Mobility-Orbitrap Mass Spectrometer: A Next-Generation
      Instrument for Native Mass Spectrometry.
AB  - A new instrument configuration for native ion mobility-mass spectrometry (IM-MS)
      is described. Macromolecule ions are generated by using a static ESI source
      coupled to an RF ion funnel, and these ions are then mobility and mass analyzed
      using a periodic focusing drift tube IM analyzer and an Orbitrap mass
      spectrometer. The instrument design retains the capabilities for first-principles
      determination of rotationally averaged ion-neutral collision cross sections and
      high-resolution measurements in both mobility and mass analysis modes for intact
      protein complexes. Operation in the IM mode utilizes FT-IMS modes (originally
      described by Knorr ( Knorr , F. J. Anal. Chem . 1985 , 57 ( 2 ), 402 - 406 )),
      which provides a means to overcome the inherent duty cycle mismatch for drift
      tube (DT)-IM and Orbitrap mass analysis. The performance of the native ESI-FT-DT
      IM-Orbitrap MS instrument was evaluated using the protein complexes Gln K (MW 44
      kDa) and streptavidin (MW 53 kDa) bound to small molecules (ADP and biotin,
      respectively) and transthyretin (MW 56 kDa) bound to thyroxine and zinc.

PMID- 30091589
TI  - Duplex Stable Isotope Labeling (DuSIL) for Simultaneous Quantitation and
      Distinction of Sialylated and Neutral N-Glycans by MALDI-MS.
AB  - Quantitative N-glycomics provides an effective tool for detecting glycosylation
      changes in cancer and other diseases. However, the lability of sialic acid and
      its lower ionization efficiency compared with that of neutral glycans make their
      analysis by mass spectrometry complicated and prevents the simultaneous
      quantitation and distinction of sialylated and neutral N-glycans by MS. To
      address this problem, we developed a novel approach duplex stable isotope
      labeling (DuSIL), to relatively quantify neutral and sialylated glycans
      concurrently by MALDI-MS. The duplex labeling strategy includes isotopic
      methylamidation labeling on the sialic acids and amino acid reductive amination
      on the reducing ends of N-glycans. Using this method, the labeled N-glycans
      showed doublet peaks with (6 + 3* N) Da mass difference for relative quantitation
      and discrimination of the number of sialic acids ( N). The DuSIL strategy is of
      high labeling efficiency, high reproducibility (CV < 20%), and good linearity (
      R2 > 0.99) within 2 orders of magnitude of dynamic range. The strategy is
      successfully applied to measure N-glycan changes of IgG from human serum with
      colorectal cancer, demonstrating its potential in relative quantitation of the N
      glycome in clinical samples.

PMID- 30091590
TI  - Poly(3,4-ethylenedioxythiophene)-Poly(styrenesulfonate)-Coated Glassy-Carbon
      Electrode for Simultaneous Voltammetric Determination of Uranium and Plutonium in
      Fast-Breeder-Test-Reactor Fuel.
AB  - Uranium (U) and plutonium (Pu) contents in nuclear materials must be maintained
      to a definite level in order to get the desired performance of the fuel inside
      the reactor. Therefore, high accuracy and precision is an essential criterion for
      the determination of U and Pu. We already reported the voltammetric determination
      of Pu in the presence of U in fast-breeder-test-reactor (FBTR) fuel samples, but
      interfacial, coupled chemical reactions between U(IV) and Pu(IV) enhance the peak
      current density of U(VI) reduction and thus make voltammetry unsuitable for the
      quantitative determination of U in the presence of Pu. Thus, developing a
      voltammetric method for the simultaneous determination of U and Pu is highly
      challenging. Herein, we report the simultaneous voltammetric determination of U
      and Pu in 1 M sulfuric acid (H2SO4) on a poly(3,4-ethylenedioxythiophene) (PEDOT)
      poly(styrenesulfonate) (PSS)-modified glassy-carbon (GC) electrode (PEDOT
      PSS/GC). The modified electrode shows enhanced performance compared with bare GC
      electrodes. The peak-current density for U(VI) reduction is enhanced in the
      presence of Pu(IV), but it attains saturation when [Pu]/[U] in solution is
      maintained >=2. Hence, under these circumstances, the variation of Pu
      concentration no longer influences the U(VI)-reduction peak, and thus the
      quantitative determination of U in the presence of Pu is possible. No
      interference is observed from commonly encountered impurities present in FBTR
      fuel samples. This method shows accuracy and precision comparable to those of the
      biamperometry method. High robustness, fast analysis, simultaneous determination,
      reduced radiation exposure to the analyst, and ease of recovery of U and Pu from
      analytical waste makes it a suitable candidate to substitute the presently
      applied biamperometry method.

PMID- 30091591
TI  - Folding Mechanism of the SH3 Domain from Grb2.
AB  - SH3 domains are small protein modules involved in the regulation of important
      cellular pathways. These domains mediate protein-protein interactions recognizing
      motifs rich in proline on the target protein. The SH3 domain from Grb2 (Grb2-SH3)
      presents the typical structure of an SH3 domain composed of two three-stranded
      antiparallel beta-sheets orthogonally packed onto each other, to form a single
      hydrophobic core. Grb2 interacts, via SH3 domain, with Gab2, a scaffolding
      disordered protein, triggering some key metabolic pathways involved in cell death
      and differentiation. In this work we report a mutational analysis (Phi value
      analysis) of the folding pathway of Grb2-SH3 that, coupled with molecular dynamic
      simulations, allows us to assess the structure of the transition state and the
      mechanism of folding of this domain. Data suggest that Grb2-SH3 folds via a
      native-like, diffused transition state with a concurrent formation of native-like
      secondary and tertiary structure (nucleation-condensation mechanism) and without
      the accumulation of folding intermediates. The comparison between our data and
      previous folding studies on SH3 domains belonging to other proteins highlights
      that proteins of this class may fold via alternative pathways, stabilized by
      different nuclei leading or not to accumulation of folding intermediates. This
      comparative analysis suggests that the alternative folding pathways for this
      class of SH3 domains can be selectively regulated by the specific amino acid
      sequences.

PMID- 30091592
TI  - Accurate Protein-Folding Transition-Path Statistics from a Simple Free-Energy
      Landscape.
AB  - A central goal of protein-folding theory is to predict the stochastic dynamics of
      transition paths-the rare trajectories that transit between the folded and
      unfolded ensembles-using only thermodynamic information, such as a low
      dimensional equilibrium free-energy landscape. However, commonly used one
      dimensional landscapes typically fall short of this aim, because an empirical
      coordinate-dependent diffusion coefficient has to be fit to transition-path
      trajectory data in order to reproduce the transition-path dynamics. We show that
      an alternative, first-principles free-energy landscape predicts transition-path
      statistics that agree well with simulations and single-molecule experiments
      without requiring dynamical data as an input. This "topological configuration"
      model assumes that distinct, native-like substructures assemble on a time scale
      that is slower than native-contact formation but faster than the folding of the
      entire protein. Using only equilibrium simulation data to determine the free
      energies of these coarse-grained intermediate states, we predict a broad
      distribution of transition-path transit times that agrees well with the
      transition-path durations observed in simulations. We further show that both the
      distribution of finite-time displacements on a one-dimensional order parameter
      and the ensemble of transition-path trajectories generated by the model are
      consistent with the simulated transition paths. These results indicate that a
      landscape based on transient folding intermediates, which are often hidden by one
      dimensional projections, can form the basis of a predictive model of protein
      folding transition-path dynamics.

PMID- 30091593
TI  - Correction to Novel Flavoalkaloids from White Tea with Inhibitory Activity
      against the Formation of Advanced Glycation End Products.

PMID- 30091594
TI  - Unraveling the Ground State and Excited State Structures and Dynamics of Hydrated
      Ce3+ Ions by Experiment and Theory.
AB  - The 4f-5d transition of Ce3+ provides favorable optical spectroscopic properties
      such as high sensitivity and quantum yield, making it a most important dopant for
      lanthanide-activated phosphors. A key for the design of these materials with fine
      tuned color emission is a fundamental understanding of the Ce3+ ground state and
      excited state structures and the dynamics of energy transfer. Such data is also
      crucial for deriving coordination chemistry information on Ce3+ ions in different
      chemical environments directly from their optical spectra. Here, by combining 4f
      5d absorption and luminescence spectroscopy and highly accurate quantum chemical
      electronic structure calculations, we study the interplay between the local
      structure of Ce3+ in aqueous solutions and in crystalline hydrates, the strengths
      of Ce-O/Cl interactions with aqua and chloride ligands, and the resulting
      absorption and luminescence spectra. Experimental and theoretical absorption
      spectra of [Ce(H2O)9]3+ and [Ce(H2O)8]3+ with defined geometries provide a means
      for analyzing the equilibrium between these species in aqueous solution as a
      function of temperature ( K(298) = 0.20 +/- 0.03), while analyses of spectra of
      different aqua-chloro complexes reveal that eight-coordinate aqua-chloro
      complexes are present in solution at high chloride concentration. An intriguing
      feature in these systems concerns the large observed Stokes shifts, 5500-10 100
      cm-1. By exploring the excited state potential energy surfaces with relativistic
      multireference calculations, we show that these shifts result from significant
      geometrical relaxation processes in the lowest 5d1 excited state. For
      [*Ce(H2O)8]3+ the relaxation gives shorter Ce-O bonds and a Stokes shift of ~5500
      cm-1, while for [*Ce(H2O)9]3+ the lowest 5d1 state results in a spontaneous
      dissociation of a water molecule and a Stokes shift of ~10 100 cm-1. These
      findings are important for the understanding and optimization of luminescence
      properties of cerium complexes.

PMID- 30091595
TI  - Accessing Polysubstituted Quinazolines via Nickel Catalyzed Acceptorless
      Dehydrogenative Coupling.
AB  - Two environmentally benign methods for the synthesis of quinazolines via
      acceptorless dehydrogenative coupling of 2-aminobenzylamine with benzyl alcohol
      (Path A) and 2-aminobenzylalcohol with benzonitrile (Path B), catalyzed by cheap,
      earth abundant and easy to prepare nickel catalysts, containing tetraaza
      macrocyclic ligands (tetramethyltetraaza[14]annulene (MeTAA) or 6,15-dimethyl
      8,17-diphenyltetraaza[14]annulene (MePhTAA)) are reported. A wide variety of
      substituted quinazolines were synthesized in moderate to high yields starting
      from cheap and easily available starting precursors. A few control reactions were
      performed to understand the mechanism and to establish the acceptorless
      dehydrogenative nature of the catalytic reactions.

PMID- 30091596
TI  - Ru-Catalyzed Cross-Dehydrogenative Coupling between Primary Alcohols to Guerbet
      Alcohol Derivatives: with Relevance for Fragrance Synthesis.
AB  - A simple method has been developed for the cross dehydrogenative coupling between
      two different primary alcohols using readily available RuCl2(PPh3)3 as a
      precatalyst through the borrowing-hydrogen approach. The present methodology is
      applicable to a large variety of alcohol derivatives including long chain
      aliphatic alcohols and heteroaryl alcohols. In addition, the methodology was
      applied in a straightforward protocol to synthesize commercially available
      fragrances such as Rosaphen and Cyclamenaldehyde in good yields.

PMID- 30091597
TI  - Predicting the Structures of Glycans, Glycoproteins, and Their Complexes.
AB  - Complex carbohydrates are ubiquitous in nature, and together with proteins and
      nucleic acids they comprise the building blocks of life. But unlike proteins and
      nucleic acids, carbohydrates form nonlinear polymers, and they are not
      characterized by robust secondary or tertiary structures but rather by
      distributions of well-defined conformational states. Their molecular flexibility
      means that oligosaccharides are often refractory to crystallization, and nuclear
      magnetic resonance (NMR) spectroscopy augmented by molecular dynamics (MD)
      simulation is the leading method for their characterization in solution. The
      biological importance of carbohydrate-protein interactions, in organismal
      development as well as in disease, places urgency on the creation of innovative
      experimental and theoretical methods that can predict the specificity of such
      interactions and quantify their strengths. Additionally, the emerging realization
      that protein glycosylation impacts protein function and immunogenicity places the
      ability to define the mechanisms by which glycosylation impacts these features at
      the forefront of carbohydrate modeling. This review will discuss the relevant
      theoretical approaches to studying the three-dimensional structures of this
      fascinating class of molecules and interactions, with reference to the relevant
      experimental data and techniques that are key for validation of the theoretical
      predictions.

PMID- 30091598
TI  - Mechanochemical Synthesis and Characterization of Metastable Hexagonal Li4SnS4
      Solid Electrolyte.
AB  - A new crystalline lithium-ion conducting material, Li4SnS4 with an ortho
      composition, was prepared by a mechanochemical technique and subsequent heat
      treatment. Synchrotron X-ray powder diffraction was used to analyze the crystal
      structure, revealing a space group of P63/ mmc and cell parameters of a =
      4.01254(4) A and c = 6.39076(8) A. Analysis of a heat-treated hexagonal Li4SnS4
      sample revealed that both lithium and tin occupied either of two adjacent
      tetrahedral sites, resulting in fractional occupation of the tetrahedral site
      (Li, 0.375; Sn, 0.125). The heat-treated hexagonal Li4SnS4 had an ionic
      conductivity of 1.1 * 10-4 S cm-1 at room temperature and a conduction activation
      energy of 32 kJ mol-1. Moreover, the heat-treated Li4SnS4 exhibited a higher
      chemical stability in air than the Li3PS4 glass-ceramic.

PMID- 30091599
TI  - [4 + 1] Cycloaddition Reaction of alpha,beta-Alkynic Hydrazones and KSCN under
      Transition-Metal-Free Conditions: Synthesis of N-Iminoisothiazolium Ylides.
AB  - A novel heteroannulation reaction between alpha,beta-alkynic hydrazones and
      potassium thiocyanate has been developed for the synthesis of N
      iminoisothiazolium ylides. The transformation features wide substrate scope,
      functional tolerance, and easy operation. This investigation involves a [4 + 1]
      type cycloaddition reaction and C-S/S-N bond formation under transition-metal
      free conditions. The application of this transformation to the gram-scale
      preparation of the N-imide ylide is also accomplished.

PMID- 30091600
TI  - A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular
      Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)
      3,3-dimethyl-1 H,2 H,3 H-pyrrolo[3,2- b]pyridin-1-yl)-2-[(2 R,5 R)-5-methyl-2
      ([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660).
AB  - Inhibitor of apoptosis proteins (IAPs) are promising anticancer targets, given
      their roles in the evasion of apoptosis. Several peptidomimetic IAP antagonists,
      with inherent selectivity for cellular IAP (cIAP) over X-linked IAP (XIAP), have
      been tested in the clinic. A fragment screening approach followed by structure
      based optimization has previously been reported that resulted in a low-nanomolar
      cIAP1 and XIAP antagonist lead molecule with a more balanced cIAP-XIAP profile.
      We now report the further structure-guided optimization of the lead, with a view
      to improving the metabolic stability and cardiac safety profile, to give the
      nonpeptidomimetic antagonist clinical candidate 27 (ASTX660), currently being
      tested in a phase 1/2 clinical trial (NCT02503423).

PMID- 30091601
TI  - Spiro-Phthalides and Isocoumarins Isolated from the Marine-Sponge-Derived Fungus
      Setosphaeria sp. SCSIO41009.
AB  - Fourteen new polyketides classified as four phthalides, setosphalides A and B, 5-
      O-desmethylcolletotrialide, and ( S)-colletotrialide (1-4), three isocoumarin
      derivatives, exserolides I-K (5-7), four pyrones, setosphapyrones A-D (8-11), one
      furanone (12), and two depsidones (13 and 14), along with 17 known polyketides
      were isolated from cultures of the sponge-derived fungus Setosphaeria sp.
      SCSIO41009. The structures and absolute configurations of these new compounds (1
      14) were determined by spectroscopic analyses, X-ray diffraction, chiral-phase
      HPLC analysis, modified Mosher's method, and comparison of ECD spectra to
      calculations. Setosphalides A (1) and B (2) are the first examples possessing a
      5,5 spiroketal skeleton in phthalide derivatives. Botryorhodines I (13) and J
      (14) showed moderate antifungal activities against the phytopathogenic fungi
      Colletotrichum asianum and Colletotrichum acutatum. Compound 18 (7- O
      demethylmonocerin) exhibited potent radical scavenging activity against DPPH.

PMID- 30091602
TI  - Vibrational States and Nitrile Lifetimes of Cyanophenylalanine Isotopomers in
      Solution.
AB  - Nitrile lifetimes and the structure of the vibrational state space of four
      isotopomers of cyanophenylalanine in solution are calculated. While the frequency
      of the nitrile of the four isotopomers decreases in the order 12C14N, 12C15N,
      13C14N, and 13C15N, the lifetime varies nonmonotonically with the change in
      frequency. The vibrational properties of the molecules that control the lifetime
      are examined. The specific resonances that contribute to the lifetime are tuned
      by isotopic substitution, and the magnitudes of the anharmonic constants involved
      in the coupling of vibrations that mediate the lifetime of the nitrile vary with
      CN mass. The nature of the modes coupled to the nitrile varies, as the frequency
      of the nitrile changes with isotopic substitution. For some CN frequencies the
      modes coupled to the CN are rather localized to the ring, while at other
      frequencies the modes coupled to the CN are more delocalized. Comparison of the
      calculated frequencies and lifetimes with recent experimental measurements on
      these molecules is discussed.

PMID- 30091603
TI  - Correction to "Contributions of Coulombic and Hofmeister Effects to the Osmotic
      Activation of Escherichia coli Transporter ProP".

PMID- 30091604
TI  - Rational Engineering of a Designed Protein Cage for siRNA Delivery.
AB  - Oligonucleotide therapeutics have transformative potential in modern medicine but
      are poor drug candidates in themselves unless fitted with compensatory carrier
      systems. We describe a simple approach to transform a designed porous protein
      cage into a nucleic acid delivery vehicle. By introducing arginine mutations to
      the lumenal surface, a positively supercharged capsule is created, which can
      encapsidate oligonucleotides in vitro with high binding affinity. We demonstrate
      that the siRNA-loaded cage is taken up by mammalian cells and releases its cargo
      to induce RNAi and knockdown gene expression. These general concepts could also
      be applied to alternative scaffold designs, expediting the development of
      artificial protein cages toward delivery applications.

PMID- 30091605
TI  - Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation
      of Sarcophytonolides.
AB  - Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of
      genus Sarcophyton. Unified total synthesis of sarcophytonolides C, E, F, G, H,
      and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS
      or SmI2-mediated fragment coupling, alkoxycarbonylallylation,
      macrolactonization, and transannular ring-closing metathesis. These total
      syntheses led to the absolute configurational confirmation of sarcophytonolide H,
      elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide
      J and isosarcophytonolide D. We also evaluated the antifouling activity and
      toxicity of the synthetic sarcophytonolides H and J and their analogues as well
      as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic
      intermediates.

PMID- 30091606
TI  - Protecting-Group-Free Total Synthesis and Biological Evaluation of 3
      Methylkealiiquinone and Structural Analogues.
AB  - The modular protecting-group-free total synthesis of 3-methylkealiiquinone, an
      analogue of the marine alkaloid kealiiquinone, was accomplished in seven steps. A
      regioselectively constructed functionalized arylbenzimidazolone moiety and
      dimethyl squarate were used as the only two building blocks. A thermal ring
      expansion via 6pi-conrotatory ring closure to build the quinone fragment gave
      rise to the desired linear analogue of the natural compound along with a
      nondescribed structurally attractive angular naphtho[1,2- d]imidazole
      regioisomer. The IC50 values for the compounds were determined on three cancer
      cell lines.

PMID- 30091607
TI  - Enantioselective Radical Cyclization of Tryptamines by Visible Light-Excited
      Nitroxides.
AB  - Nitroxides can absorb both ultraviolet (UV) and visible light, and their electron
      can be excited from the pi-bonding orbital to the antibonding pi* orbital or the
      n-bonding orbital to the antibonding pi* orbital, respectively. Despite the
      reported UV-induced hydrogen atom transfer (HAT) process, the potential of
      nitroxides for visible light-excited photosynthesis is underexplored. Here we
      demonstrate that nitroxide can convert indole to its radical through a visible
      light-induced HAT process. A chiral phosphoric acid-catalyzed cyclization of the
      in situ-formed imine radical, followed by trapping by another molecule of
      nitroxide, provides the product in high yield and enantioselectivity. To
      highlight the novelty and efficiency of this strategy, an asymmetric total
      synthesis of natural product (-)-verrupyrroloindoline was accomplished in 5
      steps.

PMID- 30091609
TI  - Axial Si-Ge Heterostructure Nanowires as Lithium-Ion Battery Anodes.
AB  - Here, we report the application of axially heterostructured nanowires consisting
      of alternating segments of silicon and germanium with a tin seed as lithium-ion
      battery anodes. During repeated lithiation and delithiation, the heterostructures
      completely rearrange into a porous network of homogeneously alloyed Si1- xGe x
      ligaments. The transformation was characterized through ex situ TEM, STEM, and
      Raman spectroscopy. Electrochemical analysis was conducted on the heterostructure
      nanowires with discharge capacities in excess of 1180 mAh/g for 400 cycles (C/5)
      and capacities of up to 613 mAh/g exhibited at a rate of 10 C.

PMID- 30091608
TI  - Simultaneous Extraction of RNA and Metabolites from Single Kidney Tissue
      Specimens for Combined Transcriptomic and Metabolomic Profiling.
AB  - Tissue analysis represents a powerful tool for the investigation of disease
      pathophysiology. However, the heterogeneous nature of tissue samples, in
      particular of neoplastic, may affect the outcome of such analysis and hence
      obscure interpretation of results. Thus, comprehensive isolation and extraction
      of transcripts and metabolites from an identical tissue specimen would minimize
      variations and enable the economic use of biopsy material which is usually
      available in limited amounts. Here we demonstrate a fast and simple protocol for
      combined transcriptomics and metabolomics analysis in homogenates prepared from
      one single tissue sample. Metabolites were recovered by protein precipitation
      from lysates originally prepared for RNA isolation and were analyzed by LC-QTOF
      MS after HILIC and RPLC separation, respectively. Strikingly, although ion
      suppression was observed, over 80% of the 2885 detected metabolic features could
      be extracted and analyzed with high reproducibility (CV <= 20%). Moreover fold
      changes of different tumor and nontumor kidney tissues were correlated to an
      established metabolomics protocol and revealed a strong correlation ( rp >=
      0.75). In order to demonstrate the feasibility of the combined analysis of RNA
      and metabolites, the protocol was applied to kidney tissue of metformin treated
      mice to investigate drug induced alterations.

PMID- 30091610
TI  - Bradyrhizobium diazoefficiens USDA 110- Glycine max Interactome Provides
      Candidate Proteins Associated with Symbiosis.
AB  - Although the legume-rhizobium symbiosis is a most-important biological process,
      there is a limited knowledge about the protein interaction network between host
      and symbiont. Using interolog- and domain-based approaches, we constructed an
      interspecies protein interactome containing 5115 protein-protein interactions
      between 2291 Glycine max and 290 Bradyrhizobium diazoefficiens USDA 110 proteins.
      The interactome was further validated by the expression pattern analysis in
      nodules, gene ontology term semantic similarity, co-expression analysis, and
      luciferase complementation image assay. In the G. max-B. diazoefficiens
      interactome, bacterial proteins are mainly ion channel and transporters of
      carbohydrates and cations, while G. max proteins are mainly involved in the
      processes of metabolism, signal transduction, and transport. We also identified
      the top 10 highly interacting proteins (hubs) for each species. Kyoto
      Encyclopedia of Genes and Genomes pathway analysis for each hub showed that a
      pair of 14-3-3 proteins (SGF14g and SGF14k) and 5 heat shock proteins in G. max
      are possibly involved in symbiosis, and 10 hubs in B. diazoefficiens may be
      important symbiotic effectors. Subnetwork analysis showed that 18 symbiosis
      related soluble N-ethylmaleimide sensitive factor attachment protein receptor
      proteins may play roles in regulating bacterial ion channels, and SGF14g and
      SGF14k possibly regulate the rhizobium dicarboxylate transport protein DctA. The
      predicted interactome provide a valuable basis for understanding the molecular
      mechanism of nodulation in soybean.

PMID- 30091611
TI  - Rapid and Effective Synthesis of alpha-Acyloxy-alpha-alkynyltrimethylsilanes.
AB  - alpha-Alkynyl-alpha'-trimethylsilylhydrazones are readily oxidized into diazo
      compounds under simple experimental conditions. These stable diazo species can in
      turn react with a range of carboxylic acids via a protonation-nucleophilic
      substitution sequence, leading to valuable alpha-acyloxy-alpha
      alkynyltrimethylsilanes. This procedure avoids the delicate preparation and
      manipulation of alpha-hydroxypropargyltrimethylsilanes.

PMID- 30091612
TI  - Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus
      Inspired Gene-Silencing Technology.
AB  - Inspired by the high gene transfer efficiency of viral vectors and to avoid side
      effects, we present here a 1D rod-like gene-silencing vector based on a plant
      virus. By decorating the transacting activator of transduction (TAT) peptide on
      the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a
      tunable isoelectric point (from ~3.5 to ~9.6) depending on the TAT dose. In
      addition to enhanced cell internalization, this plant virus-based vector (TMV
      TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage,
      resulting in both high efficiency and low cytotoxicity. By loading silencer green
      fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and
      interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro,
      the proportion of GFP-positive cells could be knocked down to levels even lower
      than 15% at a concentration of ~100% cell viability. Moreover, by interfering
      with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP)
      tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP
      negative rate as high as 80.8%. This work combines the high efficiency of viral
      vectors and the safety of nonviral vectors and may provide a promising strategy
      for gene-silencing technology.

PMID- 30091613
TI  - Visible-Light-Mediated Aerobic Oxidation of Organoboron Compounds Using in Situ
      Generated Hydrogen Peroxide.
AB  - A simple and general visible-light-mediated oxidation of organoboron compounds
      has been developed with rose bengal as the photocatalyst, substoichiometric Et3N
      as the electron donor, as well as air as the oxidant. This mild and metal-free
      protocol shows a broad substrate scope and provides a wide range of aliphatic
      alcohols and phenols in moderate to excellent yields. Notably, the robustness of
      this method is demonstrated on the stereospecific aerobic oxidation of
      organoboron compounds.

PMID- 30091614
TI  - Two-Dimensional van der Waals Heterostructures Constructed via Perovskite
      (C4H9NH3)2XBr4 and Black Phosphorus.
AB  - Heterogeneous stacking of two-dimensional (2D) perovskites with other 2D
      materials is a very effective strategy for designing low-cost and high
      performance photovoltaic and optoelectronic devices. The structural, electronic,
      and optical properties of distinctive all-2D M2XBr4-black phosphorus (BP) [M =
      (C4H9NH3)+; X = Pb2+, Sn2+, Ge2+] van der Waals (vdW) heterostructures have been
      studied by first-principle calculations. The M2SnBr4-BP and M2GeBr4-BP
      heterostructures show type-II band arrangement; however, the M2PbBr4-BP
      heterostructure exhibits type-I band arrangement. The energy level shift is
      ascribed to the difference of work function between M2XBr4 monolayer and BP
      monolayer, driving the movement of carriers spontaneously. Furthermore, the BP
      layers can enhance the light absorption of the total heterostructures, especially
      the M2GeBr4-BP heterostructure. These results indicate the all-2D perovskite and
      BP vdW heterostructures are competitive candidates for low-dimensional
      photovoltaic and optoelectronic applications.

PMID- 30091615
TI  - Phosphine-Catalyzed (3 + 2) Annulation of delta-Acetoxy Allenoates with 2
      Sulfonamidomalonate: Synthesis of Highly Substituted 3-Pyrrolines and Mechanistic
      Insight.
AB  - A mild and efficient synthetic protocol for 3-pyrrolines via the phosphine
      catalyzed (3 + 2) annulation of delta-acetoxy allenoates with 2
      sulfonamidomalonate is reported. The asymmetric version (up to 83% ee) is also
      achieved by using phosphine ( R)-SITCP as the catalyst. Mechanistic experiments
      disclose that the involved deprotonation of amide N-H and aza-addition to vinyl
      phosphonium might proceed in a concerted manner.

PMID- 30091616
TI  - Insights into Antibonding Induced Energy Density Enhancement and Exotic
      Electronic Properties for Germanium Nitrides at Modest Pressures.
AB  - Here, the electronic and bonding features in ground-state structures of germanium
      nitrides under different components that not accessible at ambient conditions
      have been systematically studied. The forming essence of weak covalent bonds
      between the Ge and N atom in high-pressure ionic crystal Fd-3 m-Ge3N4 is induced
      by the binding effect of electronic clouds originated from the Ge_ p orbitals.
      Hence, it helps us to understand the essence of covalent bond under high
      pressure, profoundly. As an excellent reducing agent, germanium transfer
      electrons to the antibonding state of the N2 dimer in Pa-3-GeN2 phase at 20 GPa,
      abnormally, weakening the bonding strength considerably than nitrogen gap (N=N)
      at ambient pressure. Furthermore, the common cognition that the atomic distance
      will be shortened under the high pressures has been broken. Amazingly, with a
      lower range of synthetic pressure (~15 GPa) and nitrogen contents (28%), its
      energy density is up to 2.32 kJ.g-1, with a similar order of magnitude than
      polymeric LiN5 (nonmolecular compound, 2.72 kJ.g-1). It breaks the universal
      recognition once again that nitrides just containing polymeric nitrogen were
      regarded as high energy density materials. Hence, antibonding induced energy
      density enhancement mechanism for low nitrogen content and pressure has been
      exposed in view of electrons. Both the highest occupied molecular orbitals (HOMO)
      and the lowest unoccupied molecular orbitals (LUMO) are usually the separated
      orbitals of N_pi* and N_sigma*, which are the key to stabilization. Besides, the
      sp2 hybridizations that exist in N4 units are responsible for the stability of
      the R-3 c-GeN4 structure and restrict the delocalization of electrons, exhibiting
      nonmetallic properties.

PMID- 30091617
TI  - Methodological considerations for assessing trauma history via self-report.
AB  - OBJECTIVE: One must first experience a traumatic event (Criterion A in the
      Diagnostic and Statistical Manual of Mental Disorders; 5th ed.; DSM-5; American
      Psychiatric Association [APA], 2013) to be diagnosed with posttraumatic stress
      disorder (PTSD). Standard procedures for assessing Criterion A (i.e., the "worst
      event" method) may result in misidentification of trauma exposure status. The
      purpose of this Internet-based study was to obtain an estimate of the percent of
      an adult sample that is misidentified as non-Criterion A through use of this
      method. METHOD: Two separate samples completed the extended version of the Life
      Events Checklist for DSM-5 (LEC-5; Weathers, Blake, et al., 2013b). Sample 1
      participants (N = 579) completed the LEC-5 via the traditional worst-event
      method, while Sample 2 participants (N = 569) completed follow-up questions for
      every event endorsed on the LEC-5, as well as a measure of posttraumatic stress
      symptoms. RESULTS: The majority of each sample identified a worst event that met
      Criterion A (Sample 1 = 58.5%; Sample 2 = 54.3%). Of the 202 participants in
      Sample 2 whose worst event did not meet Criterion A, 69.6% reported at least one
      other Criterion A event. Additionally, posttraumatic stress symptoms (i.e.,
      severity and factor structure) in Sample 2 did not differ between those with a
      worst event that met Criterion A and those with a secondary event that met
      Criterion A, even though the identified worst event did not. CONCLUSIONS: When
      assessing trauma exposure via self-report, a written narrative and follow-up
      questions should be requested for all events that are endorsed. (PsycINFO
      Database Record

PMID- 30091618
TI  - The role of emotion regulation difficulties in the connection between childhood
      emotional abuse and borderline personality features.
AB  - In the present report from the Rhode Island Methods to Improve Diagnostic
      Assessment and Services project, we examined the role of emotion dysregulation as
      a mediator between childhood abuse and borderline personality disorder (BPD)
      feature severity among a sample of 964 adults presenting for treatment at an
      outpatient clinic. A structural equation model suggested that emotional abuse
      relates to BPD features both directly and through difficulties with emotion
      regulation, whereas physical abuse showed only a weak indirect relation with BPD
      features. There was no link between sexual abuse and BPD feature severity in the
      model. Results add specificity to etiological theories of BPD and suggest that
      future research in treatment should focus on developing and strengthening emotion
      regulation strategies in clinical populations with a history of emotional abuse.
      Clinicians should be sure to assess the presence of childhood emotional abuse in
      addition to sexual and physical abuse. (PsycINFO Database Record (c) 2018 APA,
      all rights reserved).

PMID- 30091620
TI  - Team and individual influences on members' identification and performance per
      membership in multiple team membership arrangements.
AB  - Modern-day organizations often utilize team-based designs, and employees
      increasingly work simultaneously on multiple teams. These working arrangements
      have been referred to as multiple team memberships, and despite their prevalence,
      they have been the subject of relatively little research. Applying social
      identity theory as a theoretical lens, we advance a multilevel conceptual model
      that suggests both individual and team characteristics predict individuals'
      performance and satisfaction per membership, as mediated by their team
      identification per membership. We employed cross-classified effects analyses to
      model the combined influences of two sets of higher-level factors corresponding
      to individual (N = 96) and team characteristics (N = 82) on lower-level
      individual members' team identification and related outcomes per team membership
      (N = 320). Analyses of multisource temporally lagged data from software
      development professionals, who were assigned to work in multiple teams, yielded
      support for the combined influences of individual and team-level factors on
      individuals' identification with, and ultimately performance in and satisfaction
      with, their multiple team memberships. Implications for theory and practice are
      discussed. (PsycINFO Database Record

PMID- 30091621
TI  - Social-cognitive predictors of career exploration and decision-making:
      Longitudinal test of the career self-management model.
AB  - We tested the social-cognitive model of career self-management (Lent & Brown,
      2013) using a longitudinal design. Participants were 420 college students who
      completed measures of career exploration and decision-making self-efficacy,
      outcome expectations, social support, goals, and actions, along with trait
      conscientiousness, at 2 time points roughly 4 months apart, near the beginning
      and middle of an academic year. They also reported their level of career
      decidedness and decisional anxiety at both of these time points as well as near
      the end of the academic year (about 3 months after the 2nd assessment). The model
      provided good overall fit to the data and accounted for substantial portions of
      the variance in engagement in exploratory actions and in the 2 decisional
      outcomes (decidedness and decisional anxiety) over time. The findings also
      supported the hypothesized bidirectional paths of the decisional outcomes to self
      efficacy and outcome expectations. We consider implications of the findings for
      the social-cognitive model as well as for future research and practice. (PsycINFO
      Database Record

PMID- 30091622
TI  - Therapist-client agreement about their working alliance: Associations with
      attachment styles.
AB  - Recent research on attachment in therapy indicates that therapist attachment
      style is related to therapists' agreement with their clients on the quality of
      their working alliance (WA; Kivlighan & Marmarosh, 2016). This study builds on
      these findings by examining how both the therapist's and the client's attachment
      style may be related to their agreement on the WA. The authors expected that less
      anxious and less avoidant clients working with less anxious and less avoidant
      therapists would have higher WA agreement. Using hierarchical linear modeling,
      they analyzed archival session data from 158 clients and 27 therapists at a
      community clinic. In terms of overall level agreement (averaged across sessions),
      therapists and clients significantly disagreed on their WA ratings, with
      therapists rating the WA lower than did their clients; but there was more
      therapist-client level-agreement when therapists had relatively less attachment
      avoidance. In terms of (linear) WA agreement from session to session, the authors
      found no main effects for either therapist or client attachment style alone, but
      several significant interactions between therapist and client attachment styles.
      Session-to-session agreement on the WA was higher when clients and therapist had
      "matching" (both higher or both lower in attachment anxiety or attachment
      avoidance) or "complementary" (one higher in attachment avoidance, the other
      lower in attachment anxiety, or one higher in attachment anxiety, the other lower
      in attachment avoidance) attachment styles than when styles were
      noncomplementary. The authors discuss these findings in terms of the attachment
      related communication, signaling, and behavior that may be occurring in therapy
      dyads. (PsycINFO Database Record

PMID- 30091623
TI  - Practice recommendations for addressing racism: A content analysis of the
      counseling psychology literature.
AB  - Although racism persists as a significant public health issue that adversely
      impacts the mental health of people of color (U.S. Department of Health and Human
      Service, 2001), there has been very little systematic guidance for mental health
      professionals to address racism through practice (S. Harrell, 2000). Therefore,
      we conducted a content analysis of the peer reviewed counseling psychology
      literature-the first of its kind-to provide a summary and critique of the extant
      practice recommendations and facilitate the development and enhancement of
      practice efforts aimed at addressing racism. We reviewed racism-related articles
      published in the Journal of Counseling Psychology, The Counseling Psychologist,
      and Counseling Psychology Quarterly and identified 73 relevant articles, of which
      51 provided practice recommendations. Based on our review of this literature, we
      identified eight general categories of recommendations for addressing racism:
      psychoeducation, validation, self-awareness and critical consciousness, critical
      examination of privilege and racial attitudes, culturally responsive social
      support, developing positive identity, externalize/minimize self-blame, and
      outreach and advocacy. We found that most recommendations within each category
      were at the individual level with far fewer at the group and systemic level. A
      critique of recommendations is provided along with suggestions for developing and
      bolstering practice, research, and consultation efforts aimed at addressing
      racism. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30091619
TI  - The retrosplenial-parietal network and reference frame coordination for spatial
      navigation.
AB  - The retrosplenial cortex is anatomically positioned to integrate sensory, motor,
      and visual information and is thought to have an important role in processing
      spatial information and guiding behavior through complex environments. Anatomical
      and theoretical work has argued that the retrosplenial cortex participates in
      spatial behavior in concert with input from the parietal cortex. Although the
      nature of these interactions is unknown, a central position is that the
      functional connectivity is hierarchical with egocentric spatial information
      processed in the parietal cortex and higher-level allocentric mappings generated
      in the retrosplenial cortex. Here, we review the evidence supporting this
      proposal. We begin by summarizing the key anatomical features of the
      retrosplenial-parietal network, and then review studies investigating the neural
      correlates of these regions during spatial behavior. Our summary of this
      literature suggests that the retrosplenial-parietal circuitry does not represent
      a strict hierarchical parcellation of function between the two regions but
      instead a heterogeneous mixture of egocentric-allocentric coding and integration
      across frames of reference. We also suggest that this circuitry should be
      represented as a gradient of egocentric-to-allocentric information processing
      from parietal to retrosplenial cortices, with more specialized encoding of global
      allocentric frameworks within the retrosplenial cortex and more specialized
      egocentric and local allocentric representations in parietal cortex. We conclude
      by identifying the major gaps in this literature and suggest new avenues of
      research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30091624
TI  - Direct, indirect, and buffering effects of support for mothers on children's
      socioemotional adjustment.
AB  - Support for mothers may improve children's socioemotional adjustment, yet few
      studies have considered the benefits of formal support (from health and social
      work professionals) in addition to social support (from family and friends) or
      explored the mechanisms. These issues were addressed using a birth cohort (n =
      2,649) to explore how mothers' perceptions of social and formal support when
      children were ages 10-22 months predicted trajectories of children's
      externalizing and internalizing problems from 58 to 122 months. We tested
      mediating pathways from support to child adjustment via 3 family stressors
      measured at 46-58 months (maternal distress, economic strain, and dysfunctional
      parenting) and examined whether support buffered effects of stressors on child
      adjustment. Social and formal support were simultaneously associated with lower
      child externalizing and internalizing problem trajectory intercepts at 90 months
      but did not predict trajectory slopes. Social support effects were mediated
      mainly via lower maternal distress, which then reduced children's problems via
      lower dysfunctional parenting, or more directly. Additional indirect effects
      involved lower economic strain. Formal support effects were mediated to a lesser
      extent by reduced dysfunctional parenting. Two buffering effects were found:
      social support reduced effects of economic strain on internalizing problems, and
      formal support reduced effects of dysfunctional parenting on internalizing
      problems. Findings suggest measures promoting families' social integration should
      benefit children's socioemotional adjustment via improved parental psychological
      and economic resources and by buffering impacts of economic strain. Enhancing
      access to health and welfare services through greater awareness and trust should
      benefit children's adjustment, via improved parenting and by buffering impacts of
      dysfunctional parenting. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30091626
TI  - "A review and meta-analysis of age-based stereotype threat: Negative stereotypes,
      not facts, do the damage": Correction to Lamont, Swift, and Abrams (2015).
AB  - Reports an error in "A review and meta-analysis of age-based stereotype threat:
      Negative stereotypes, not facts, do the damage" by Ruth A. Lamont, Hannah J.
      Swift and Dominic Abrams (Psychology and Aging, 2015[Mar], Vol 30[1], 180-193).
      In the article, some of the effect sizes in the meta-analysis were mistakenly
      calculated based on standard error (SE), rather than standard deviation (SD). The
      authors identified this problem for three of the 32 studies in the analysis. In
      addition, SE was incorrectly used in one of the original publications (Desrichard
      & Kopetz, 2005), and amendments have been made based on this also. A table of the
      recalculated data is provided in the erratum. The recalculations have minimal
      impact on the meta-analysis conclusions, but effect sizes calculated throughout
      the article needed to be updated. The meta-analysis still revealed a small-to
      medium effect of age-based stereotype threat (ABST; d= .32). Two conclusions have
      changed from the original moderator analyses. Journal region did not
      significantly moderate effect sizes of stereotype-based studies conducted within
      Europe (Qbetween (1) 2.17, p .14). Thus, reassuringly, it cannot be concluded
      that publication region predicts effect size magnitude or that there are
      different expectations for effect sizes based on the journal region. Because this
      issue was slightly peripheral to the central questions for the analysis, the
      central conclusions of the article remain unaffected. Further, the meta-analysis
      now supports the authors' initial hypothesis that gender would moderate ABST
      effects ( beta=.36, p< .05), whereby women may experience greater ABST effects.
      The online version of this article has been corrected. (The following abstract of
      the original article appeared in record 2015-02669-001.) Stereotype threat
      effects arise when an individual feels at risk of confirming a negative
      stereotype about their group and consequently underperforms on stereotype
      relevant tasks (Steele, 2010). Among older people, underperformance across
      cognitive and physical tasks is hypothesized to result from age-based stereotype
      threat (ABST) because of negative age-stereotypes regarding older adults'
      competence. The present review and meta-analyses examine 22 published and 10
      unpublished articles, including 82 effect sizes (N = 3882) investigating ABST on
      older people's (Mage = 69.5) performance. The analysis revealed a significant
      small-to-medium effect of ABST (d = .28) and important moderators of the effect
      size. Specifically, older adults are more vulnerable to ABST when (a) stereotype
      based rather than fact-based manipulations are used (d = .52); (b) when
      performance is tested using cognitive measures (d = .36); and (c) occurs reliably
      when the dependent variable is measured proximally to the manipulation. The
      review raises important theoretical and methodological issues, and areas for
      future research. (PsycINFO Database Record

PMID- 30091625
TI  - The importance of time to think back: The role of reminding in retroactive
      effects of memory.
AB  - Change has been described as detrimental for later memory for the original event
      in research on retroactive interference. Popular accounts of retroactive
      interference treat learning as the formation of simple associations and explain
      interference as due to response competition, perhaps along with unlearning or
      inhibition of the original response. By such accounts, providing additional study
      time for a changed response in a classic A-B, A-D learning paradigm should
      increase retroactive interference. In contrast, our experiments show that
      changing a response produces retroactive facilitation rather than retroactive
      interference but that outcome requires that the change be detected in the form of
      a reminding. When reminding does not occur, retroactive interference is observed.
      Increasing time to study the changed response increases the likelihood of being
      reminded. Accounts in terms of simple associations cannot explain the importance
      of reminding. We do so by assuming that being reminded results in a recursive
      representation that includes both the original and changed response along with
      the order in which they occurred. We discuss the importance of our results for
      application as well as for theory. (PsycINFO Database Record

PMID- 30091627
TI  - Social relationship quality buffers negative affective correlates of everyday
      solitude in an adult lifespan and an older adult sample.
AB  - Aging takes place in a social context but older adults also spend a significant
      amount of their time alone. Solitude (the objective state of being alone and
      without social interaction) has been associated with negative experiences but
      also with specific benefits. We examine the importance of social relationships
      for time-varying associations between affective experiences and solitude. Using
      repeated daily life assessments from an adult life span sample (Study 1, N = 183,
      age: 20-81 years) and an older adult sample (Study 2, N = 97, age: 50-85 years),
      we examined the moderating role of social relationship quality on within-person
      solitude-affect associations. Data were analyzed using multilevel models
      controlling for gender, age, overall amount of time in solitude, retirement
      status, marital status, education, and current work activity. Higher relationship
      quality was associated with higher average affective well-being. Compared to
      being with others, participants reported lower levels of high-arousal positive
      affect (PA) during solitude in both studies. In Study 1, solitude was also
      associated with higher levels of low-arousal negative affect (NA) and higher
      levels of low-arousal PA compared to when with others. Across both studies,
      individuals with higher quality relationships reported lesser increases in low
      arousal NA when in solitude, as compared to individuals with lower quality
      relationships. Findings highlight that solitude is experienced less negatively
      for individuals embedded in a context of higher quality social relationships.
      Thus, preservation and promotion of social resources in older adulthood may be
      important to ward off potential negative ramifications of spending a significant
      amount of time alone. (PsycINFO Database Record

PMID- 30091628
TI  - Affective well-being in the last years of life: The role of health decline.
AB  - Adding to recent evidence of terminal decline in affective well-being, this study
      examined the role of physical health in accounting for time-to-death-related
      changes in positive affect (PA) and negative affect (NA). We distinguished
      effects of preterminal health levels predicting levels ("preserved
      differentiation") and terminal changes ("differential preservation") and of
      terminal health declines predicting terminal changes ("terminal reactivity") of
      affective well-being in the terminal period of life. Data were used from the
      first cohort of the Longitudinal Aging Study Amsterdam, including 3-yearly
      measurements from 1992-1993 to 2011-2012 (N = 2310, age = 55-85 at baseline).
      Measures of PA and NA were derived from the Center for Epidemiologic Studies
      Depression Scale. Health measures included self-rated health, self-reported
      functional limitations, and gait speed. Exponential time-to-death-related
      trajectories in PA and NA were analyzed with mixed regression models. Results
      confirmed accelerated time-to-death-related decline of PA and increase of NA.
      Regarding health effects, the findings support terminal reactivity, in that the
      amount of end-of-life changes in affective well-being was closely linked to the
      concurrent terminal changes in health. Preterminal health levels did not predict
      the amount of terminal changes in affective well-being; however, reaching the
      final years of life with better levels of functional health appeared to promote
      longer maintenance of better levels of affective well-being and terminal declines
      more "compressed" to a shorter period prior to death. The findings point to needs
      to strengthen individuals' resources to compensate for health losses at the end
      of their life span. (PsycINFO Database Record

PMID- 30091629
TI  - Perceived constraints in late midlife: Cohort differences in the Longitudinal
      Aging Study Amsterdam (LASA).
AB  - Life span psychological and life course sociological perspectives have long
      acknowledged the role of historical and sociocultural contexts for individuals'
      functioning and development. Secular increases favoring older adults in later
      born cohorts are widely documented for fluid cognitive performance and well
      being. However, less is known about secular trends in further key resources of
      psychosocial functioning, such as perceptions of constraints, and how these are
      driven by and associated with well-established and probably interrelated secular
      trends in several individual difference characteristics, including
      sociodemographic, religiosity, physical health, cognitive, and social variables.
      To examine these questions, we compared data from 2 independent local samples of
      the Longitudinal Aging Study Amsterdam (LASA) obtained 20 years apart, in 1992
      1993 (n1992-1993 = 795; age = 55-65 years) versus in 2012-2013 (n2012-2013 = 819;
      age = 55-65 years). Results revealed that in late midlife, people today perceive
      fewer constraints than did same-aged peers 20 years ago. These secular trends
      remained after covarying for individual and cohort differences in physical
      health, performance-based measures of cognitive functioning (memory),
      quantitative and qualitative indicators of social support, and self-esteem. The
      effect size was in the moderate range (d = -.20). We conclude that secular trends
      such as perceptions of constraints in people's lives generalize to key
      psychosocial resources across adulthood and old age. We discuss potential
      underlying mechanisms and consider practical implications of our findings.
      (PsycINFO Database Record

PMID- 30091630
TI  - Mental rotation training in older adults: The role of practice and strategy.
AB  - There is evidence of mental rotation (MR) abilities responding to training even
      in older adults, but it is still not clear whether such training would have
      generalized and maintained effects. The aim of the present study was to examine
      the specific short- and long-term gains, and any transfer effects, induced by
      rotation training in healthy older adults. The study involved 43 healthy older
      adults: 14 practiced with 2 MR tasks, that is, a 3D same/different comparisons
      task and a Tetris game (the Mental Rotation [MR] group); 15 were trained to use a
      strategy based on concrete object manipulation and imagery, then practiced with
      the 2 rotation tasks (Strategy [S] + MR group); and 14 were involved in
      alternative nonspatial activities (active control group). Transfer and
      maintenance effects were assessed (after 1 month) using tasks similar to those
      used in the training (criterion tasks), different spatial tasks (mental rotation
      and perspective taking tasks) and a fluid intelligence task. The results showed a
      trend toward an improvement in successive training sessions. The S + MR and MR
      groups both gained substantially more than the active control group in the short-
      and long-term, in the criterion tasks and most of the tasks testing transfer
      effects. The S + MR group showed greater long-term gains than the MR group in
      most tasks. These findings support a positive effect of rotation training in
      older adults, particularly when associated with strategy use. (PsycINFO Database
      Record

PMID- 30091632
TI  - Exploring dedifferentiation across the adult lifespan.
AB  - One of the central concepts within the literature on cognitive aging is the
      notion of dedifferentiation-the idea that increasing age is associated with an
      increase in the interrelatedness of different cognitive abilities. Despite the
      centrality of this dedifferentiation hypothesis, there is a great deal of
      evidence that both supports and does not support dedifferentiation. We
      hypothesized that these inconsistent findings were due to (a) the use of
      different cognitive abilities (i.e., memory vs. speed of processing) that were
      correlated; and (b) the differing age groups that were used across studies. By
      using data from 11 well-validated cognitive test batteries (K = 2,355, range of
      the mean ages of correlations 18-85+), we found evidence for linear
      dedifferentiation when a test assessing speed of processing was included in the
      correlation with test of other cognitive abilities. We speculate that previous
      findings of nonlinear dedifferentiation are likely a result of undiagnosed or
      unrecognized pathology in a subsample of participants. (PsycINFO Database Record

PMID- 30091631
TI  - Visual short-term memory through the lifespan: Preserved benefits of context and
      metacognition.
AB  - Visual short-term memory (VSTM) ability falls throughout the life span in healthy
      adults. Using a continuous report task, in a large, population-based sample, we
      first confirmed that this decline affects the quality and quantity of reported
      memories as well as knowledge of which item went where. Visual and sensorimotor
      precision also worsened with advancing age, but this did not account for the
      reduced memory performance. We then considered two strategies that older
      individuals might be able to adopt, to offset these memory declines: the use of
      contextual encoding, and metacognitive monitoring of performance. Context and
      metacognitive awareness were both associated with significantly better
      performance, however these effects did not interact with age in our sample. This
      suggests that older adults retain their capacity to boost memory performance
      through attention to external context and monitoring of their performance.
      Strategies that focus on taking advantage of these preserved abilities may
      therefore help to maintain VSTM performance with advancing age. The article
      reports on analysis of the Cambridge Centre for Ageing and Neuroscience (Cam-CAN)
      data. (PsycINFO Database Record

PMID- 30091633
TI  - The effects of attention and adaptation duration on the motion aftereffect.
AB  - The motion aftereffect (MAE) is the perception of illusory motion following
      extended exposure to a moving stimulus. The MAE has been used to probe the role
      of attention in motion processing. Many studies have reported that MAEs are
      reduced if attention is diverted from the adaptation stimulus, but others have
      argued that motion adaptation is independent of attention. We explored several
      factors that might modulate the attention-adaptation relationship and therefore
      explain apparent inconsistencies, namely (a) adaptation duration, (b) motion
      type: translating versus complex, and (c) response bias. Participants viewed
      translating (Experiments 1a and 2) or rotating (Experiment 1b) random dot
      patterns while fixating a central letter stream. During adaptation, participants
      reported brief changes in the adaptor speed (attention-focused) or the presence
      of white vowels within the letter stream (attention-diverted). Trials consisted
      of multiple adaptation-test cycles, and the MAE was measured after each
      adaptation period. Across experiments, focused attention produced significantly
      larger MAEs than did diverted attention (15% change, Cohen's d = .41). Attention
      affected the MAE asymptote, rather than its accumulation rate, and had larger
      effects for translational than for complex motion. The effect of attention
      remained evident after controlling for response bias. Our results suggest that
      attention affects multiple levels of the motion-processing hierarchy: not only
      higher level motion processing, as seen with apparent motion, but also low-level
      motion processing, as evidenced by the MAE. (PsycINFO Database Record (c) 2018
      APA, all rights reserved).

PMID- 30091634
TI  - Visual working memory supports perceptual stability across saccadic eye
      movements.
AB  - Vision is suppressed during saccadic eye movements. To create a stable perception
      of the visual world we must compensate for the gaps in visual input caused by
      this suppression. Some theories of perceptual stability, such as the Saccade
      Target Object Theory (McConkie & Currie, 1996), propose that stability relies on
      object correspondence across saccades. According to these views, the visual
      system encodes features of the saccade target into visual working memory (VWM)
      before a saccade is made. After the saccade, participants attempt to locate those
      features within a small region near the fovea. If this locating process succeeds,
      perceptual stability is maintained. The present study investigated directly
      whether perceptual stability relies on VWM. If it does, perceived stability
      should be impaired when VWM is loaded with other visual information. Participants
      detected saccade target displacements while simultaneously maintaining a VWM or
      verbal working memory (AWM) load. In three experiments, a VWM load negatively
      impacted participants' ability to detect saccade target displacements and the
      saccade target displacement task negatively impacted memory for VWM task items.
      Neither of these effects were apparent when AWM was loaded, suggesting that
      performance on VWM and saccade target displacement detection tasks, and thus
      perceptual stability, relies on VWM resources. (PsycINFO Database Record (c) 2018
      APA, all rights reserved).

PMID- 30091635
TI  - Temporal constraints in the use of auditory action effects for motor
      optimization.
AB  - For quick ballistic movements the possibility of making online adjustments is
      limited. However, when the same action (e.g., pressing a button) is repeated
      multiple times, trial-by-trial adjustments are possible: Previous studies found
      that participants utilized auditory effects as feedback to optimize the applied
      force for such tone eliciting actions. In the current study, it was examined
      whether this action-effect-related motor adaptation also occurred if a delay was
      inserted between the action and its auditory effect. In 2 experiments,
      participants applied force impulses to a force-sensitive resistor in a self-paced
      schedule. Action-effect delay was manipulated between experimental blocks in the
      0- to 1,600-ms range. The level of motor adaptation diminished as a function of
      action-effect delay, with no adaptation observable for delays longer than 200 ms,
      which indicates that action-effect contingency in itself is not sufficient to
      warrant that sensory effects will be useful for action control. A third
      experiment also showed that the observed temporal constraint was not absolute:
      Adaptation at 200-ms delay was stronger in a group of participants who were
      exposed to 400-ms action-tone delays before testing, than in a group exposed to a
      0-ms action-tone delay, suggesting that action-effect-related motor adaptation is
      influenced by prior experience. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30091637
TI  - Tactile confusions of the fingers and toes.
AB  - Recent research has shown systematic patterns of confusions between digits of the
      hands and feet. The present study addressed whether such confusions arise from
      early somatosensory maps or higher level body representations. As the glabrous
      and hairy skin of the hands and feet have distinct representations in
      somatosensory cortex, an effect arising from early somatotopic maps may show
      distinct patterns on each skin surface. In contrast, if the effect arises from
      higher level body representations which represent the digits as volumetric units,
      similar patterns should be apparent regardless of which side of the digit is
      touched. We obtained confusion matrices showing the pattern of mislocalization on
      the glabrous and hairy skin surfaces of the toes (Experiment 1) and fingers
      (Experiment 2). Our results replicated the characteristic pattern of
      mislocalizations found on the glabrous skin reported in previous studies.
      Critically, these effects were highly similar on the hairy skin surface of both
      the toes and fingers. Despite the pattern of mislocalizations being highly
      stereotyped across participants, there were consistent individual differences in
      the pattern of confusions across the two skin surfaces. These results suggest
      that mislocalizations occur at the level of individual digits, consistent with
      their resulting from higher level body representations. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30091638
TI  - Effects of lexical ambiguity on perception: A test of the label feedback
      hypothesis using a visual oddball paradigm.
AB  - We used a visual oddball paradigm to investigate whether a shared verbal label
      makes two objects belonging to different conceptual categories less perceptually
      distinct. In Experiment 1, the critical images shared a label as well as some
      perceptual features (orange, referring to the color and the fruit), and in
      Experiment 2, the critical images shared a label but no perceptual features (bat,
      referring to the animal and the sports equipment). In both experiments comparison
      images were similar to each of the critical images but they did not share a
      label. A reduced deviant-related negativity (DRN) was observed for critical
      images compared with comparison images in both experiments, suggesting that the
      critical image pairs were perceived as less distinct than comparison pairs. These
      results extend previous research using the visual oddball paradigm that has shown
      that images from the same conceptual category are perceived as more distinct when
      they have different labels, and provide further support for the label-feedback
      hypothesis (Lupyan, 2012) in which language is assumed to modulate perception
      online. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30091636
TI  - Mapping the dynamic allocation of temporal attention in musical patterns.
AB  - Many environmental sounds, such as music or speech, are patterned in time.
      Dynamic attending theory, and supporting empirical evidence, suggests that a
      stimulus's temporal structure serves to orient attention to specific moments in
      time. One instantiation of this theory posits that attention synchronizes to the
      temporal structure of a stimulus in an oscillatory fashion, with optimal
      perception at salient time points or oscillation peaks. We examined whether a
      model consisting of damped linear oscillators succeeds at predicting temporal
      attention behavior in rhythmic multi-instrumental music. We conducted 3
      experiments in which we mapped listeners' perceptual sensitivity by estimating
      detection thresholds for intensity deviants embedded at multiple time points
      within a stimulus pattern. We compared participants' thresholds for detecting
      intensity changes at various time points with the modeled salience prediction at
      each of those time points. Across all experiments, results showed that the
      resonator model predicted listener thresholds, such that listeners were more
      sensitive to probes at time points corresponding to greater model-predicted
      salience. This effect held for both intensity increment and decrement probes and
      for metrically simple and complex stimuli. Moreover, the resonator model
      explained the data better than did predictions based on canonical metric
      hierarchy or auditory scene density. Our results offer new insight into the
      temporal orienting of attention in complex auditory scenes using a parsimonious
      computational model for predicting attentional dynamics. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30091639
TI  - The paddle effect in the pong task is not due to blocking ability of the
      observer.
AB  - When participants try to block a moving ball on a screen by means of a manually
      controlled paddle, their perception of the ball's speed is altered as a function
      of the paddle size and thus of their blocking performance. In particular, the
      ball appears to move slower the larger the paddle is. This paddle effect was
      investigated in several studies and has become a prominent example for influences
      of observers' ability to act on perception. Three experiments were conducted to
      test for this action-related explanation. The results were clear-cut. The paddle
      effect occurred even though a possible impact of observers' action ability on
      perception was experimentally eliminated. This outcome strongly suggests that the
      paddle effect is not due to action ability as previously assumed. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30091640
TI  - Surface curvature from kinetic depth can affect lightness.
AB  - The light reaching the eye confounds the proportion of light reflected from
      surfaces in the environment with their illumination. To achieve constancy in
      perceived surface reflectance (lightness) across variations in illumination, the
      visual system must infer the relative contribution of reflectance to the incoming
      luminance signals. Previous studies have shown that contour and stereo cues to
      surface shape can affect the lightness of sawtooth luminance profiles. Here, we
      investigated whether cues to surface shape provided solely by motion (via the
      kinetic depth effect) can similarly influence lightness. Human observers judged
      the relative brightness of patches contained within abutting surfaces with
      identical luminance ramps. We found that the reported brightness differences were
      significantly lower when the kinetic depth effect supported the impression of
      curved surfaces, compared to similar conditions without the kinetic depth effect.
      This demonstrates the capacity of the visual system to use shape from motion to
      "explain away" alternative interpretations of luminance gradients, and supports
      the cue-invariance of the interaction between shape and lightness. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30091642
TI  - Assessment of adherence to medication in patients after myocardial infarction
      treated with percutaneous coronary intervention. Is there a place for newself
      reported questionnaires?
AB  - INTRODUCTION: Non-adherence to medication regimen after myocardial infarction
      (MI) leads to increased morbidity and mortality and generates additional cost to
      the healthcare system. OBJECTIVES: The aim of this systematic review was to
      critically discuss assessment methods of adherence to medication in patients
      after myocardial infarction treated with percutaneous coronary intervention and
      the possible application of a new self-reported questionnaire. METHODS: A
      systematic investigation of all published literature was conducted to minimize
      the risk of bias. A database search (PubMed, CENTRAL and Google Scholar
      databases) from January 1998 through December 2017. RESULTS: Adequate assessment
      of patient adherence to treatment is necessary to understand the potential for
      adverse outcomes. Methods developed for adherence evaluation are classified as
      subjective and objective or as direct and indirect. Direct, objective measures
      reflect pharmacokinetics and include measurement of the drug or its metabolite
      concentration, evaluation of the presence of biological markers given with the
      drug and direct observation of patients' medication-taking behavior. Several
      indirect, objective methods are based on evaluation of the availability of
      prescribed medications assuming that medication is taken exactly as prescribed.
      Assessment of the effectiveness of treatment, both at the pharmacodynamic and
      clinical level, indirectly but objectively reflects adherence to treatment.
      Subjective methods, including patient-kept diaries, patient interviews and self
      reported questionnaires, due to their simplicity, real-time feedback and low
      cost, are often used for adherence evaluation in clinical practice. CONCLUSIONS:
      In spite of the availability, convenience and variety of methods, measuring
      adherence still remains a real challenge. Using a well designed questionnaire
      provides an opportunity to identify patients at increased risk of non-adherence
      and the obstacles impeding implementation of the treatment plan, allowing
      implementation of tailored interventions in order to improve patient medication
      taking behavior.

PMID- 30091641
TI  - WDR62 mediates TNFalpha-dependent JNK activation via TRAF2-MLK3 axis.
AB  - The mitogen-activated protein kinases (MAPKs) regulate a variety of cellular
      processes. The three main MAPK cascades are the extracellular signal-regulated
      kinases (ERK), c-Jun N-terminal kinase (JNK), and p38 kinases. A typical MAPK
      cascade is composed of MAP3K-MAP2K-MAPK kinases that are held by scaffold
      proteins. Scaffolds function to assemble the protein tier and contribute to the
      specificity and efficacy of signal transmission. WD repeat domain 62 (WDR62) is a
      JNK scaffold protein, interacting with JNK, MKK7, and several MAP3Ks. The loss of
      WDR62 in human leads to microcephaly and pachygyria. Yet the role of WDR62 in
      cellular function is not fully studied. We used the CRISPR/Cas9 and short hairpin
      RNA approaches to establish a human breast cancer cell line MDA-MB-231 with WDR62
      loss of function and studied the consequence to JNK signaling. In growing cells,
      WDR62 is responsible for the basal expression of c-Jun. In stressed cells, WDR62
      specifically mediates TNFalpha-dependent JNK activation through the association
      with both the adaptor protein, TNF receptor-associated factor 2 (TRAF2), and the
      MAP3K protein, mixed lineage kinase 3. TNFalpha-dependent JNK activation is
      mediated by WDR62 in HCT116 and HeLa cell lines as well. MDA-MB-231 WDR62
      knockout cells display increased resistance to TNFalpha-induced cell death.
      Collectively, WDR62 coordinates the TNFalpha receptor signaling pathway to JNK
      activation through association with multiple kinases and the adaptor protein
      TRAF2.

PMID- 30091643
TI  - Intra-articular treatment with corticosteroids increases apoptosis in human
      rotator cuff tears.
AB  - PURPOSE: The aim of this study is to evaluate in vivo the level of apoptosis in
      human rotator cuff tears and the relationship it might have with tendon
      degeneration. METHODS: Rotator cuff biopsies from 19 male and female patients,
      ages between 38 and 68 years, with and without previous corticosteroid
      infiltrations were collected via arthroscopy. Biopsies from seven patients with
      healthy rotator cuffs were used as a control group. An in situ terminal
      deoxynucleotidyl transferase dUTP nick end labeling assay was performed to detect
      the level of apoptosis, which was expressed as a percentage of apoptotic cells
      (PAC). RESULTS: PAC in patients with corticosteroid infiltrations was 76.97 +/-
      16.99 in all tendon rupture zones, in non-infiltrated patients was 35.89 +/-
      22.96, whereas in control patients was 14.48 +/- 8.15. Likewise, the tendency of
      PAC reveals that apoptosis in control and non-infiltrated groups was different
      and dispersed in all tear zones; while in corticosteroid treated patients, the
      tendency was similar in all rupture sites. CONCLUSIONS: This investigation leads
      us to conclude that the administration of corticosteroid is associated with a
      higher amount of apoptosis at the insertion site of the rotator cuff (rupture
      edge).

PMID- 30091645
TI  - Incorporation and evaluation of serial concept maps for vertical integration and
      clinical reasoning in case-based learning tutorials: Perspectives of students
      beginning clinical medicine.
AB  - BACKGROUND: Concept maps and case-based learning (CBL) are recognized and useful
      strategies to enhance undergraduate medical learning. However, research on the
      use of a mixed approach is limited. AIMS: To incorporate serial concept mapping
      (CM) into CBL tutorials, to explore students' perspectives on the worth of the
      method to better understand patients' problems and elicit diagnoses, and to
      assess the student's learning. METHODS: We designed a four-phase method of CBL
      that incorporated serial mapping to assist students in the process of knowledge
      construction regarding the underlying principles of the patients' present
      complaints, the recognition of disease patterns and the eliciting of diagnostic
      hypotheses. Students worked both individually and collaboratively. We used a
      questionnaire to explore the students' perspectives of the method and a score
      system to assess end-of-course performance. RESULTS: The students perceived that
      serial CM was useful to integrate previous knowledge into new clinical
      information for case analysis and to elicit diagnoses. They also reported an
      increase in content-related knowledge. The end-of-course scores were high for
      most students. CONCLUSIONS: Novice medical students perceived serial CM in CBL
      tutorials as an effective strategy for learning. End-of-course examination scores
      indicated that they improved case analysis and clinical reasoning skills.

PMID- 30091644
TI  - CRISPR/Cas9-based gene targeting using synthetic guide RNAs enables robust cell
      biological analyses.
AB  - A key goal for cell biological analyses is to assess the phenotypes that result
      from eliminating a target gene. Since the early 1990s, the predominant strategy
      utilized in human tissue culture cells has been RNA interference (RNAi)-mediated
      protein depletion. However, RNAi suffers well-documented off-target effects as
      well as incomplete and reversible protein depletion. The implementation of
      CRISPR/Cas9-based DNA cleavage has revolutionized the capacity to conduct
      functional studies in human cells. However, this approach is still underutilized
      for conducting visual phenotypic analyses, particularly for essential genes that
      require conditional strategies to eliminate their gene products. Optimizing this
      strategy requires effective and streamlined approaches to introduce the Cas9
      guide RNA into target cells. Here we assess the efficacy of synthetic guide RNA
      transfection to eliminate gene products for cell biological studies. On the basis
      of three representative gene targets (KIF11, CENPN, and RELA), we demonstrate
      that transfection of synthetic single guide RNA (sgRNA) and CRISPR RNA (crRNA)
      guides works comparably for protein depletion as cell lines stably expressing
      lentiviral-delivered RNA guides. We additionally demonstrate that synthetic
      sgRNAs can be introduced by reverse transfection on an array. Together, these
      strategies provide a robust, flexible, and scalable approach for conducting
      functional studies in human cells.

PMID- 30091646
TI  - Bolstering diagnostic reasoning skills with adaptive learning.
AB  - PURPOSE: Adaptive learning emerges when precise assessment informs delivery of
      educational materials. This study will demonstrate how data from Human Dx, a case
      based e-learning platform, can characterize an individual's diagnostic reasoning
      skills, and deliver tailored content to improve accuracy. METHODS: Pearson Chi
      square analysis was used to assess variability in accuracy across three groups of
      participants (attendings, residents, and medical students) and three categories
      of cases (core medical, surgical, and other). Logistic regression analyses were
      conducted to explore the relationship between solve duration and accuracy. Mean
      accuracy and duration were calculated for 370 individuals. Repeated measures
      analysis of variance (ANOVA) were used to assess variability for an individual
      solver across the three categories. RESULTS: There were significant differences
      in accuracy across the three groups and the three categories (p < 0.001).
      Individual solvers have significant variance in accuracy across the three
      categories. Shorter solve duration predicted higher accuracy. Patterns of
      performance were identified; four profiles are highlighted to demonstrate
      potential adaptive learning interventions. CONCLUSIONS: Human Dx can assess
      diagnostic reasoning skills. When weaknesses are identified, adaptive learning
      strategies can push content to promote skill development. This has implications
      for customizing curricular elements to improve the diagnostic skills of
      healthcare professionals.

PMID- 30091647
TI  - Cost of subcutaneous immunotherapy in a large insured population in the United
      States.
AB  - OBJECTIVE: Allergic rhinitis (AR) affects up to 40% of the United States
      population, with approximately $11 billion annual medical costs. Allergy
      immunotherapy is the best option for long-term symptomatic relief, but treatment
      compliance can be low. The objective was to describe subcutaneous immunotherapy
      (SCIT)-related costs for patients overall and those with inconsistent treatment.
      METHODS: This study observed commercial and Medicare Advantage with Part D health
      plan enrollees. Included subjects had claims with AR diagnostic codes during 1
      January 2011-31 December 2015 and >=1 SCIT claim during 1 January 2013-31
      December 2015 (index date = first SCIT claim date). A control sample was chosen
      randomly at a 1:3 ratio of SCIT to controls. Inconsistent use was defined as a
      >=90 day gap after >=1 SCIT. Patient characteristics were compared between SCIT
      patients and controls. Costs were calculated for all SCIT patients and the
      inconsistent subgroup. RESULTS: Compared with controls (n = 394,479), SCIT (n =
      131,493) patients were younger (39.3 vs. 41.4 years), more likely female (56.4%
      vs. 50.7%) and more likely in a commercial plan (91.6% vs. 83.6%); all p < .001.
      Among SCIT patients, 15.1% had inconsistent use. Among all SCIT patients, the 3
      year total plan-paid SCIT-related costs were $205,741,125 (18% was for
      inconsistent subgroup) and patient-paid costs were $47,560,450 (15% for
      inconsistent). Per-member-per-month costs were $0.48 plan-paid and $0.11 patient
      paid, with $0.09 plan-paid and $0.02 patient-paid for inconsistent use.
      CONCLUSIONS: This study showed 15% of patients may have costly inconsistent SCIT
      treatment. Greater understanding is needed regarding the reasons for inconsistent
      use of subcutaneous allergy immunotherapy.

PMID- 30091648
TI  - How would we combat menopause as an Alzheimer's risk factor?

PMID- 30091650
TI  - Accelerating expertise: Perceptual and adaptive learning technology in medical
      learning.
AB  - RATIONALE: Recent advances in the learning sciences offer remarkable potential
      for improving medical learning and performance. Difficult to teach pattern
      recognition skills can be systematically accelerated using techniques of
      perceptual learning (PL). The effectiveness of PL interventions is amplified when
      they are combined with adaptive learning (AL) technology in perceptual-adaptive
      learning modules (PALMs). INNOVATION: Specifically, PALMs incorporate the
      Adaptive Response Time-based Sequencing (ARTS) system, which leverages learner
      performance (accuracy and speed) in interactive learning episodes to guide the
      course of factual, perceptual, or procedural learning, optimize spacing, and lead
      learners to comprehensive mastery. Here we describe elements and scientific
      foundations of PL and its embodiment in learning technology. We also consider
      evidence that AL systems utilizing both accuracy and speed enhance learning
      efficiency and provide a unified account and potential optimization of spacing
      effects in learning, as well as supporting accuracy, transfer, and fluency as
      goals of learning. RESULTS: To illustrate this process, we review some results of
      earlier PALMs and present new data from a PALM designed to accelerate and improve
      diagnosis in electrocardiography. CONCLUSIONS: Through relatively short training
      interventions, PALMs produce large and durable improvements in trainees'
      abilities to accurately and fluently interpret clinical signs and tests, helping
      to bridge the gap between novice and expert clinicians.

PMID- 30091649
TI  - The shared role of the Rsr1 GTPase and Gic1/Gic2 in Cdc42 polarization.
AB  - The Cdc42 GTPase plays a central role in polarity development in many species. In
      budding yeast, Cdc42 is essential for polarized growth at the proper site and
      also for spontaneous cell polarization in the absence of spatial cues. Cdc42
      polarization is critical for multiple events in the G1 phase prior to bud
      emergence, including bud-site assembly, polarization of the actin cytoskeleton,
      and septin filament assembly to form a ring at the new bud site. Yet the
      mechanism by which Cdc42 polarizes is not fully understood. Here we report that
      biphasic Cdc42 polarization in the G1 phase is coupled to stepwise assembly of
      the septin ring for bud emergence. We show that the Rsr1 GTPase shares a
      partially redundant role with Gic1 and Gic2, two related Cdc42 effectors, in the
      first phase of Cdc42 polarization in haploid cells. We propose that the first
      phase of Cdc42 polarization is mediated by positive feedback loops that function
      in parallel-one involving Rsr1 via local activation of Cdc42 in response to
      spatial cues and another involving Gic1 or Gic2 via reduction of diffusion of
      active Cdc42.

PMID- 30091651
TI  - The leucine-rich region of Flightless I interacts with R-ras to regulate cell
      extension formation.
AB  - Flightless I (FliI) is a calcium-dependent, actin severing and capping protein
      that localizes to cell matrix adhesions, contributes to the generation of cell
      extensions, and colocalizes with Ras. Currently, the mechanism by which FliI
      interacts with Ras to enable assembly of actin-based cell protrusions is not
      defined. R-Ras, but not K-ras, H-ras, or N-ras, associated with the leucine-rich
      region (LRR) of FliI. Mutations of the proline-rich region of R-ras (P202A,
      P203A) prevented this association. Knockdown of Ras GTPase-activating SH3 domain
      binding protein (G3BP1) or Rasgap120 by small interfering RNA inhibited the
      formation of cell extensions and prevented interaction of R-ras and G3BP1 in FliI
      wild-type (WT) cells. Pull-down assays using G3BP1 fusion proteins showed a
      strong association of R-ras with the C-terminus of G3BP1 (amino acids 236-466),
      which also required the LRR of FliI. In cells that expressed the truncated N
      terminus or C-terminus of G3BP1, the formation of cell extensions was blocked.
      Endogenous Rasgap120 interacted with the N-terminus of G3BP1 (amino acids 1-230).
      We conclude that in cells plated on collagen FliI-LRR interacts with R-ras to
      promote cell extension formation and that FliI is required for the interaction of
      Rasgap120 with G3BP1 to regulate R-ras activity and growth of cell extensions.

PMID- 30091652
TI  - A within-trial cost-effectiveness analysis of panitumumab compared with
      bevacizumab in the first-line treatment of patients with wild-type RAS metastatic
      colorectal cancer in the US.
AB  - AIMS: This analysis investigated the cost-effectiveness of panitumumab plus
      mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) compared with bevacizumab
      plus mFOLFOX6 in the first-line treatment of patients with wild-type RAS
      metastatic colorectal cancer (mCRC). MATERIALS AND METHODS: The cost
      effectiveness analysis was developed from a third-party payer perspective in the
      US and was implemented using a partitioned survival model with health states for
      first-line treatment (progression-free), disease progression with and without
      subsequent active treatment, and death. Survival analyses of patients with wild
      type RAS mCRC from the PEAK head-to-head clinical trial of panitumumab vs
      bevacizumab were performed to estimate time in the model health states.
      Additional data from PEAK informed the amount of each drug consumed, duration of
      therapy, subsequent therapy use, and toxicities related to mCRC treatment.
      Literature and US public data sources were used to estimate unit costs associated
      with treatment and duration of subsequent active therapies. Utility weights were
      calculated from patient-level data from panitumumab trials in the first-, second
      , and third-line settings. A life-time perspective was taken with future costs
      and outcomes discounted at 3% per annum. Scenario, one-way, and probabilistic
      sensitivity analyses were performed. RESULTS: Compared with bevacizumab, the use
      of panitumumab resulted in an incremental cost of US $60,286, and an incremental
      quality-adjusted life-year (QALY) of 0.445, translating into a cost per QALY
      gained of US $135,391 in favor of panitumumab. Results were sensitive to wastage
      and dose rounding assumptions modeled. LIMITATIONS: Progression-free and overall
      survival were extrapolated beyond the follow-up of the primary analysis using
      fitted parametric curves. Costs and quality of life were estimated from multiple
      and different data sources. CONCLUSIONS: The efficacy of panitumumab in extending
      progression-free and overall survival and improving quality of life makes it a
      cost-effective option for first-line treatment of patients with wild-type RAS
      mCRC compared with bevacizumab.

PMID- 30091654
TI  - Hepatitis C virus infection in children: How do we prevent it and how do we treat
      it?
AB  - INTRODUCTION: Hepatitis C virus (HCV) infection is an important contributor to
      the worldwide burden of liver-related morbidity and mortality. Mother-to-child
      transmission of HCV ranges from 6 to 11% in different populations globally, but
      accurate estimates on the burden of pediatric HCV infection are limited because
      screening approaches are not consistent. Areas covered: The advent of new direct
      acting antiviral agents that achieve very high rates of sustained virologic
      response (representing virologic cure) with short (i.e. 8-12 weeks) regimens has
      revolutionized the field of HCV treatment and led to the development of global
      elimination goals for HCV transmission and mortality. However, information on
      their safety during pregnancy and efficacy in preventing mother-to-child
      transmission is lacking. Currently, there are no approved treatment regimens with
      these antiviral agents for children younger than 12 years of age. Expert
      commentary: If these agents are shown to be safe during pregnancy and effective
      in preventing transmission to the infant, screening of pregnant women and
      antenatal treatment of those infected, could pave the way for eliminating
      pediatric HCV infection- particularly as these drugs become less costly and more
      accessible. Treatment of infected children when indicated, along with universal
      safe health care practices, can further pediatric HCV elimination.

PMID- 30091653
TI  - Cancer cells' ability to mechanically adjust to extracellular matrix stiffness
      correlates with their invasive potential.
AB  - Increased tissue stiffness is a classic characteristic of solid tumors. One of
      the major contributing factors is increased density of collagen fibers in the
      extracellular matrix (ECM). Here, we investigate how cancer cells biomechanically
      interact with and respond to the stiffness of the ECM. Probing the adaptability
      of cancer cells to altered ECM stiffness using optical tweezers-based
      microrheology and deformability cytometry, we find that only malignant cancer
      cells have the ability to adjust to collagen matrices of different densities.
      Employing microrheology on the biologically relevant spheroid invasion assay, we
      can furthermore demonstrate that, even within a cluster of cells of similar
      origin, there are differences in the intracellular biomechanical properties
      dependent on the cells' invasive behavior. We reveal a consistent increase of
      viscosity in cancer cells leading the invasion into the collagen matrices in
      comparison with cancer cells following in the stalk or remaining in the center of
      the spheroid. We hypothesize that this differential viscoelasticity might
      facilitate spheroid tip invasion through a dense matrix. These findings highlight
      the importance of the biomechanical interplay between cells and their
      microenvironment for tumor progression.

PMID- 30091655
TI  - Remodeling neuronal ER-PM junctions is a conserved nonconducting function of Kv2
      plasma membrane ion channels.
AB  - The endoplasmic reticulum (ER) and plasma membrane (PM) form junctions crucial to
      ion and lipid signaling and homeostasis. The Kv2.1 ion channel is localized at ER
      PM junctions in brain neurons and is unique among PM proteins in its ability to
      remodel these specialized membrane contact sites. Here, we show that this
      function is conserved between Kv2.1 and Kv2.2, which differ in their biophysical
      properties, modulation, and cellular expression. Kv2.2 ER-PM junctions are
      present at sites deficient in the actin cytoskeleton, and disruption of the actin
      cytoskeleton affects their spatial organization. Kv2.2-containing ER-PM junctions
      overlap with those formed by canonical ER-PM tethers. The ability of Kv2 channels
      to remodel ER-PM junctions is unchanged by point mutations that eliminate their
      ion conduction but eliminated by point mutations within the Kv2-specific proximal
      restriction and clustering (PRC) domain that do not impact their ion channel
      function. The highly conserved PRC domain is sufficient to transfer the ER-PM
      junction-remodeling function to another PM protein. Last, brain neurons in Kv2
      double-knockout mice have altered ER-PM junctions. Together, these findings
      demonstrate a conserved in vivo function for Kv2 family members in remodeling
      neuronal ER-PM junctions that is distinct from their canonical role as ion
      conducting channels shaping neuronal excitability.

PMID- 30091657
TI  - Positron emission tomography imaging in evaluation of MS pathology in vivo.
AB  - Positron emission tomography (PET) gives an opportunity to quantitate the
      expression of specific molecular targets in vivo and longitudinally in brain and
      thus enhances our possibilities to understand and follow up multiple sclerosis
      (MS)-related pathology. For successful PET imaging, one needs a relevant target
      molecule within the brain, to which a blood-brain barrier-penetrating specific
      radioligand will bind. 18-kDa translocator protein (TSPO)-binding radioligands
      have been used to detect activated microglial cells at different stages of MS,
      and remyelination has been measured using amyloid PET. Several PET ligands for
      the detection of other inflammatory targets, besides TSPO, have been developed
      but not yet been used for imaging MS patients. Finally, synaptic density
      evaluation has been successfully tested in human subjects and gives opportunities
      for the evaluation of the development of cortical and deep gray matter pathology
      in MS. This review will discuss PET imaging modalities relevant for MS today.

PMID- 30091656
TI  - Effects of human sex chromosome dosage on spatial chromosome organization.
AB  - Sex chromosome aneuploidies (SCAs) are common genetic syndromes characterized by
      the presence of an aberrant number of X and Y chromosomes due to meiotic defects.
      These conditions impact the structure and function of diverse tissues, but the
      proximal effects of SCAs on genome organization are unknown. Here, to determine
      the consequences of SCAs on global genome organization, we have analyzed multiple
      architectural features of chromosome organization in a comprehensive set of
      primary cells from SCA patients with various ratios of X and Y chromosomes by use
      of imaging-based high-throughput chromosome territory mapping (HiCTMap). We find
      that X chromosome supernumeracy does not affect the size, volume, or nuclear
      position of the Y chromosome or an autosomal chromosome. In contrast, the active
      X chromosome undergoes architectural changes as a function of increasing X copy
      number as measured by a decrease in size and an increase in circularity, which is
      indicative of chromatin compaction. In Y chromosome supernumeracy, Y chromosome
      size is reduced suggesting higher chromatin condensation. The radial positioning
      of chromosomes is unaffected in SCA karyotypes. Taken together, these
      observations document changes in genome architecture in response to alterations
      in sex chromosome numbers and point to trans-effects of dosage compensation on
      chromosome organization.

PMID- 30091659
TI  - Learning to balance efficiency and innovation for optimal adaptive expertise.
AB  - It is critical for health professionals to continue to learn and this must be
      supported by health professions education (HPE). Adaptive expert clinicians are
      not only expert in their work but have the additional capacity to learn and
      improve in their practices. The authors review a selective aspect of learning to
      become an adaptive expert: the capacity to optimally balance routine approaches
      that maximize efficiency with innovative ones where energy and resources are used
      to customize actions for novel or difficult situations. Optimal transfer of
      learning, and hence the design of instruction, differs depending on whether the
      goal is efficient or innovative practice. However, the task is necessarily
      further complicated when the aspiration is an adaptive expert practitioner who
      can fluidly balance innovation with efficiency as the situation requires. Using
      HPE examples at both the individual and organizational level, the authors explore
      the instructional implications of learning to shift from efficient to innovative
      expert functioning, and back. They argue that the efficiency-innovation tension
      is likely to endure deep into the future and therefore warrants important
      consideration in HPE.

PMID- 30091658
TI  - The in situ structures of mono-, di-, and trinucleosomes in human
      heterochromatin.
AB  - The in situ three-dimensional organization of chromatin at the nucleosome and
      oligonucleosome levels is unknown. Here we use cryo-electron tomography to
      determine the in situ structures of HeLa nucleosomes, which have canonical core
      structures and asymmetric, flexible linker DNA. Subtomogram remapping suggests
      that sequential nucleosomes in heterochromatin follow irregular paths at the
      oligonucleosome level. This basic principle of higher-order repressive chromatin
      folding is compatible with the conformational variability of the two linker DNAs
      at the single-nucleosome level.

PMID- 30091660
TI  - Relationship between postoperative volume of macroadenomas and clinical outcome
      after endoscopic trans-sphenoidal resection.
AB  - PURPOSE: Although symptoms are expected to improve after the resection of
      pituitary macroadenomas, tumor resection volume does not always correlate with
      the patient's symptoms. Our objectives were to assess the pre and postoperative
      volumes of pituitary macroadenomas before, immediately after surgery and at
      follow-up, and to explore possible associations and correlations among these
      changes and symptoms. MATERIALS AND METHODS: We retrospectively reviewed the
      clinical records and the preoperative and postoperative magnetic resonance
      imaging studies at 24 hours and at 3, 6 and 9 months follow-up of 146 patients
      who underwent surgery for pituitary macroadenomas. We measured tumor volumes
      before and after surgery and compared changes with symptom improvement. RESULTS:
      The mean preoperative tumor volume was 24.66 cm3 (standard deviation 65.18 cm3,
      95% confidence interval (CI) 14-35.32). The most common symptoms were
      visual/cranial nerve abnormalities (65%) and headaches (56%). Immediately after
      surgery, symptoms persisted without significant changes in all patients. A
      progressive tumor volume decrease was noted during follow-up, and symptoms
      improved in 78% of patients. Despite no imaging evidence of chiasm or cavernous
      sinus compression, 32 patients showed no symptom improvement. Patients with
      symptoms for more than 1 year (mean duration of symptoms 26 months, SD 24.3, 95%
      CI 22.03-29.97 months) had a higher risk of the persistence of symptoms compared
      to patients with a mean duration of symptoms of less than 1 year (odds ratio 2.5,
      95% CI 2.4-3, P < 0.005). CONCLUSIONS: The duration of symptoms prior of surgery
      is a more important factor than tumor resection volume alone when considering the
      long-term outcome of symptoms. Furthermore, lack of symptom improvement in the
      immediate postoperative period does not necessarily represent an inadequate
      resection.

PMID- 30091663
TI  - Lower cutaneous microvascular reactivity in adult cancer patients receiving
      chemotherapy.
AB  - Cancer patients with a history of anticancer chemotherapy are at an increased
      cardiovascular disease risk compared with cancer-free populations. Therefore, we
      tested the hypothesis that cancer patients receiving adjuvant chemotherapy would
      have a lower cutaneous microvascular reactivity and lower endothelium-dependent
      flow-mediated dilation (FMD) of the brachial artery compared with matched cancer
      free control subjects. To test this hypothesis, we performed a case control study
      with seven cancer patients receiving adjuvant chemotherapy and seven matched
      healthy reference control subjects. Red blood cell flux was measured as an index
      of cutaneous blood flow via laser Doppler flowmetry. Acetylcholine (ACh)-mediated
      vasodilation was determined by iontophoresis. Data were expressed as percent
      increase in cutaneous vascular conductance. Endothelium-dependent FMD of the
      brachial artery via ultrasonography was determined as an index of macrovessel
      endothelial function. Cutaneous microvascular reactivity was attenuated in cancer
      patients compared with control subjects [cancer: 959.9 +/- 187.3%, control:
      1,556.8 +/- 222.2%; P = 0.03, effect size (ES) = 1.1]. Additionally, cancer
      patients demonstrated a significantly lower area under the curve response to ACh
      iontophoresis compared with healthy control subjects. Brachial artery FMD was
      also significantly lower in cancer patients compared with control subjects
      (cancer: 2.2 +/- 0.6%, control: 6.6 +/- 1.4%; P = 0.006, ES = 1.6), which was
      significantly associated with measurements of microvascular reactivity. These
      findings suggest that decreases in vascular reactivity can occur during cancer
      chemotherapy, which may have implications for the long-term risk of
      cardiovascular disease morbidity and mortality. NEW & NOTEWORTHY Cancer survivors
      treated with chemotherapy experience an increased risk of cardiovascular events,
      linked to both cardiac and vascular toxicity. The major finding of this study is
      that microvascular reactivity and macrovascular endothelium-dependent flow
      mediated dilation are lower in cancer patients currently receiving adjuvant
      chemotherapy compared with healthy counterparts.

PMID- 30091662
TI  - White-matter integrity in patients with systemic lupus erythematosus and memory
      deficits.
AB  - PURPOSE: Cognitive dysfunction is common in neuropsychiatric systemic lupus
      erythematosus (SLE). Memory is a commonly affected cognitive domain. Clinically,
      however, it is difficult to detect memory deficits. The objective of this study
      is to evaluate whether normal controls and SLE patients with and without memory
      deficit differ in terms of white-matter integrity. METHODS: Twenty SLE patients
      with memory deficit were compared to 47 SLE patients without memory deficit and
      22 sex-, age-, and education-matched control individuals. Diffusion tensor
      imaging (DTI) was performed in a 1.5-Tesla scanner. For tract-based spatial
      statistics analysis, a white-matter skeleton was created. A permutation-based
      inference with 5000 permutations with a threshold of p < 0.05 was used to
      identify abnormalities in fractional anisotropy (FA). The mean diffusivity (MD),
      radial diffusivity (RD) and axial diffusivity (AD) were also projected onto the
      mean FA skeleton. RESULTS: Compared to controls, SLE patients with and without
      memory deficit had decreased FA in: bilateral anterior thalamic radiation,
      inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate
      fasciculus, corticospinal tract, genu, and body of the corpus callosum. SLE
      patients with and without memory deficit also presented increased MD and RD
      values compared to controls in these areas. Comparison between SLE patients with
      and without memory deficit did not present significant differences in DTI
      parameters. CONCLUSION: DTI can detect extensive abnormalities in the normal
      appearing white matter of SLE patients with and without memory deficit, compared
      to controls. However, there was no difference, in terms of white-matter
      integrity, between the groups of SLE patients.

PMID- 30091664
TI  - Acclimatization of low altitude-bred deer mice (Peromyscus maniculatus) to high
      altitude.
AB  - A colony of deer mice subspecies (Peromyscus maniculatus sonoriensis) native to
      high altitude (HA) has been maintained at sea level for 18-20 generations and
      remains genetically unchanged. To determine if these animals retain
      responsiveness to hypoxia, one group (9-11 weeks old) was acclimated to HA
      (3,800m) for 8 weeks. Age-matched control animals were acclimated to a lower
      altitude (LA, 252m). Maximal O2 uptake (VO2max) was measured at the respective
      altitudes. On a separate day, lung volume, diffusing capacity for carbon monoxide
      (DLCO) and pulmonary blood flow were measured under anesthesia using a
      rebreathing technique at two inspired O2 tensions. The HA-acclimated deer mice
      maintained a normal VO2max relative to low-altitude baseline. Compared to LA
      control mice, antemortem lung volume was larger in HA mice in a manner dependent
      on alveolar O2 tension. Systemic hematocrit, pulmonary blood flow and
      standardized DLCO did not differ significantly between groups. HA mice showed a
      higher postmortem alveolar-capillary hematocrit, larger alveolar ducts and
      smaller distal conducting structures. In HA mice, absolute volumes of alveolar
      type-I epithelium and endothelium were higher while that of interstitium was
      lower than in LA mice. These structural changes occurred without a net increase
      in whole-lung septal tissue-capillary volumes or surface areas. Thus, deer mice
      bred and raised to adulthood at low altitude retain phenotypic plasticity and
      adapt to high altitude without a decrement in VO2max via structural (enlarged
      airspaces, alveolar septal remodeling) and non-structural (lung expansion under
      hypoxia) mechanisms and without an increase in systemic hematocrit or
      compensatory lung growth.

PMID- 30091661
TI  - Spectrin regulates cell contractility through production and maintenance of actin
      bundles in the Caenorhabditis elegans spermatheca.
AB  - Disruption to the contractility of cells, including smooth muscle cells of the
      cardiovascular system and myoepithelial cells of the glandular epithelium,
      contributes to the pathophysiology of contractile tissue diseases, including
      asthma, hypertension, and primary Sjogren's syndrome. Cell contractility is
      determined by myosin activity and actomyosin network organization and is mediated
      by hundreds of protein-protein interactions, many directly involving actin. Here
      we use a candidate RNA interference screen of more than 100 Caenorhabditis
      elegans genes with predicted actin-binding and regulatory domains to identify
      genes that contribute to the contractility of the somatic gonad. We identify the
      spectrin cytoskeleton composed of SPC-1/alpha-spectrin, UNC-70/beta-spectrin, and
      SMA-1/beta heavy-spectrin as required for contractility and actin organization in
      the myoepithelial cells of the C. elegans spermatheca. We use imaging of fixed
      and live animals as well as tissue- and developmental-stage-specific disruption
      of the spectrin cytoskeleton to show that spectrin regulates the production of
      prominent central actin bundles and is required for maintenance of central actin
      bundles throughout successive rounds of stretch and contraction. We conclude that
      the spectrin cytoskeleton contributes to spermathecal contractility by promoting
      maintenance of the robust actomyosin bundles that drive contraction.

PMID- 30091665
TI  - RESPONSES OF SKELETAL MUSCLE SIZE AND ANABOLISM ARE REPRODUCIBLE WITH MULTIPLE
      PERIODS OF UNLOADING/RELOADING.
AB  - AIM: Mechanical unloading has long been understood to contribute to rapid and
      substantial adaptations within skeletal muscle, most notably muscle atrophy.
      Studies have often demonstrated that many of the alterations resulting from
      disuse are reversed with a reintroduction of load and have supported the concept
      of muscle plasticity. We hypothesized that adaptations during disuse and recovery
      was a repeatable/reproducible phenomenon, which we tested with repeated changes
      in mechanical load. METHODS: Rats were assigned to one of the following five
      groups: animals undergoing one or two bouts of hindlimb unloading (28-d), with or
      without recovery (56-d), or control. Following the completion of their final time
      point, posterior crural muscles were studied. RESULTS: Muscle sizes were lower
      following 28-d of disuse but fully recovered with a 56-d reloading period,
      regardless of the number of disuse/recovery cycles. Mixed protein fractional
      synthesis rates consistently reflected mass and loading conditions (supported by
      anabolic signaling); whereas the myofibrillar protein synthesis response varied
      among muscles. Amino acid concentrations were assessed in the gastrocnemius free
      pool, and did not correlate with muscle atrophy associated with mechanical
      unloading. Muscle collagen concentrations were higher following the second
      unloading period and remained elevated following 56-d of recovery. CONCLUSION:
      Anabolic responses to alterations in load are preserved throughout multiple
      perturbations, but repeated periods of unloading may cause additive strain to
      muscle structure (collagen). This study suggests that while mass and anabolism
      are reproducibly reflective of the loading environment, repeated exposure to
      unloading and/or reloading may impact the overall structural integrity of muscle.

PMID- 30091666
TI  - Losartan has no additive effect on the response to heavy resistance exercise in
      human elderly skeletal muscle.
AB  - PURPOSE: To investigate the potential of blocking the angiotensin II type I
      receptor (AT1R) on the hypertrophy response of elderly human skeletal muscle to
      four months of heavy resistance exercise training. METHODS: 58 healthy elderly
      men (+65 years) were randomized into three groups, consuming either AT1R blocker
      (losartan, 100mg/day) or placebo for 4 months. Two groups performed resistance
      training (RT) and were treated with either losartan or placebo and one group did
      not train but was treated with losartan. Quadriceps muscle biopsies, MR scans and
      strength tests were performed at baseline and after 8 and 16 weeks. Biopsies were
      sectioned for immunohistochemistry to determine the number of satellite cells,
      capillaries, fibre type distribution and fibre area. Gene expression levels of
      myostatin, connective tissue and myogenic signalling pathways were determined by
      real time RT-PCR. RESULTS: Four months of heavy resistance training lead in both
      training groups to expected improvements in quadriceps (~3-4%) and vastus
      lateralis (~5-6%) cross sectional area, type II fibre area (~10-18%), as well as
      dynamic (~13%) and isometric (~19%) quadriceps peak force, but with absolutely no
      effect of losartan on these outcomes. Further, no changes were seen in satellite
      cell number with training and most gene targets failed to show any changes
      induced by training or losartan treatment. CONCLUSION: There does not appear to
      be any effect of AT1R blocking in elderly men during four months of resistance
      training. Therefore, we do not find any support for using AT1R blockers for
      promoting muscle adaptation to training in humans.

PMID- 30091667
TI  - Skeletal muscle fiber characteristics in patients with chronic heart failure:
      impact of disease severity and relation with muscle oxygenation during exercise.
AB  - INTRODUCTION: Skeletal muscle function in patients with heart failure and reduced
      ejection fraction (HFrEF) greatly determines exercise capacity. However, reports
      on skeletal muscle fiber dimensions, fiber capillarization, and their
      physiological importance are inconsistent. METHODS: Twenty-five moderately
      impaired patients with HFrEF and 25 healthy control (HC) subjects underwent
      muscle biopsy sampling. Type I and type II muscle fiber characteristics were
      determined by immunohistochemistry. In patients with HFrEF, enzymatic oxidative
      capacity was assessed, and pulmonary oxygen uptake (VO2) and skeletal muscle
      oxygenation during maximal and moderate-intensity exercise were measured using
      near-infrared spectroscopy. RESULTS: While muscle fiber cross-sectional area
      (CSA) was not different between patients with HFrEF and HC, percentage of type I
      fibers was higher in HC (46+/-15% versus 37+/-12%, respectively, P=0.041). Fiber
      type distribution and CSA were not different between patients in New York Heart
      Association (NYHA) class II and III. Type I muscle fiber capillarization was
      higher in HFrEF compared with controls (capillary-to-fiber perimeter exchange
      (CFPE) index: 5.70+/-0.92 versus 5.05+/-0.82, respectively, P=0.027). Patients in
      NYHA class III had slower VO2 and muscle deoxygenation kinetics during onset of
      exercise, and lower muscle oxidative capacity than those in class II (P<0.05).
      Also, fiber capillarization was lower, but not compared with HC. Higher CFPE
      index was related to faster deoxygenation (rspearman=-0.682, P=0.001), however,
      not to muscle oxidative capacity (r=-0.282, P=0.216). CONCLUSIONS: Type I muscle
      fiber capillarization is higher in HFrEF compared with HC, but not in patients
      with greater exercise impairment. Greater capillarization may positively affect
      VO2 kinetics by enhancing muscle oxygen diffusion.

PMID- 30091668
TI  - Low but not high frequency of intermittent hypoxia suppresses endothelium
      dependent, oxidative stress-mediated contractions in carotid arteries of obese
      mice.
AB  - Obstructive sleep apnea is characterized by intermittent hypoxia (IH) during
      sleep and predisposes to endothelial dysfunction. Obesity is a major risk factor
      for the occurrence of sleep apnea. The present study compared the functional
      impact of low (IH10; 10 hypoxic events/hour) and high (IH60; 60 hypoxic
      events/hour) frequency IH during four weeks on endothelial function in male
      C57BL/6 mice with or without high fat (HF) diet-induced obesity. Mean arterial
      blood pressure (tail cuff method) was increased in obese mice after IH60
      exposure, i.e. HF+IH60 group. The serum levels of the oxidative stress marker
      malondialdehyde were augmented in lean IH60 and HF groups, with a further
      increase in HF+IH60 but a reduction in HF+IH10 mice compared to the HF group.
      Vascular responsiveness was assessed as changes in isometric tension in isolated
      arteries. Relaxations to the endothelium-dependent vasodilator acetylcholine were
      impaired in HF+IH60 aortae. Endothelium-dependent contractions (EDC; response to
      acetylcholine in the presence of the nitric oxide synthase inhibitor L-NAME) in
      carotid arteries were augmented in the HF group, but this HF-induced augmentation
      was suppressed by low frequency IH exposure. The addition of apocynin
      (antioxidant) reduced EDC in HF and HF+IH60 groups but not in HF+IH10 group. In
      conclusion, these findings suggest that exposure of obese mice to mild IH exerts
      preconditioning-like suppression of endothelium-dependent and oxidative stress
      mediated contractions. When IH severity increases, this suppression diminishes
      and endothelial dysfunction accelerates.

PMID- 30091669
TI  - Child-adult differences in neuromuscular fatigue are muscle-dependent.
AB  - The aim of this study was to compare the development and etiology of
      neuromuscular fatigue of the knee extensor (KE) and plantar flexor (PF) muscles
      during repeated maximal voluntary isometric contractions (MVIC) between children
      and adults. Twenty-one prepubertal boys (9-11 years) and 24 men (18-30 years)
      performed two fatigue protocols consisting in a repetition of 5-s isometric MVIC
      of the KE or PF muscles interspersed with 5-s passive recovery periods until MVIC
      reached 60% of its initial value. The etiology of neuromuscular fatigue of the KE
      and PF muscles was investigated by means of non-invasive methods such as the
      surface electromyography, single and doublet magnetic stimulation, twitch
      interpolation technique and NIRS. The number of repetitions performed was
      significantly lower in men (15.4 +/- 3.8) than boys (38.7 +/- 18.8) for the KE
      fatigue test. In contrast, no significant difference was found for the PF muscles
      between boys and men (12.1 +/- 4.9 and 13.8 +/- 4.9 repetitions, respectively).
      Boys displayed a lower reduction in potentiated twitch torque, low-frequency
      fatigue and muscle oxygenation than men whatever the muscle group considered. In
      contrast, voluntary activation level and normalized EMG data decreased to a
      greater extent in boys than men for both muscle groups. To conclude, boys
      experienced less peripheral and more central fatigue during repeated MVICs than
      men whatever the muscle group considered. However, child-adult differences in
      neuromuscular fatigue were muscle-dependent since boys fatigued similarly to men
      with the PF muscles and to a lower extent with the KE muscles than men.

PMID- 30091671
TI  - Identification and characterization of protein cross-links induced by oxidative
      reactions.
AB  - INTRODUCTION: Protein cross-links are common in biological systems and are
      generated both deliberately as a part of normal metabolism and also accidently as
      a result of exposure to external factors such as oxidation and glycation
      stresses. These cross-links can be both positive and negative for biological
      function, with high levels of inappropriate cross-links being associated with
      multiple human pathologies, as well as loss of protein structure and function in
      the food, agricultural, and pharmaceutical fields. Areas covered: This review
      covers recent advances in the detection and identification of protein cross-links
      arising from oxidation reactions, mediated by both radicals and two-electron
      oxidants. Information on both enzymatic and nonenzymatic cross-linking is
      reviewed, both where this is intentional, as part of normal metabolism, and
      accidental and a potential cause of disease. Expert commentary: The advantages
      and drawbacks of various methods available for the detection, identification, and
      quantification of these species are discussed, as well as some of the mechanisms
      and processes known to give rise to these species.

PMID- 30091670
TI  - Cholesterol depletion enhances TGF-beta Smad signaling by increasing c-Jun
      expression through a PKR-dependent mechanism.
AB  - Transforming growth factor-beta (TGF-beta) plays critical roles in numerous
      physiological and pathological responses. Cholesterol, a major plasma membrane
      component, can have pronounced effects on signaling responses. Cells continually
      monitor cholesterol content and activate multilayered transcriptional and
      translational signaling programs, following perturbations to cholesterol
      homeostasis (e.g., statins, the commonly used cholesterol-reducing drugs).
      However, the cross-talk of such programs with ligand-induced signaling responses
      (e.g., TGF-beta signaling) remained unknown. Here, we studied the effects of a
      mild reduction in free (membrane-associated) cholesterol on distinct components
      of TGF-beta-signaling pathways. Our findings reveal a new regulatory mechanism
      that enhances TGF-beta-signaling responses by acting downstream from receptor
      activation. Reduced cholesterol results in PKR-dependent eIF2alpha
      phosphorylation, which enhances c-Jun translation, leading in turn to higher
      levels of JNK-mediated c-Jun phosphorylation. Activated c-Jun enhances
      transcription and expression of Smad2/3. This leads to enhanced sensitivity to
      TGF-beta stimulation, due to increased Smad2/3 expression and phosphorylation.
      The phospho/total Smad2/3 ratio remains unchanged, indicating that the effect is
      not due to altered receptor activity. We propose that cholesterol depletion
      induces overactivation of PKR, JNK, and TGF-beta signaling, which together may
      contribute to the side effects of statins in diverse disease settings.

PMID- 30091672
TI  - The ribosome receptors Mrx15 and Mba1 jointly organize cotranslational insertion
      and protein biogenesis in mitochondria.
AB  - Mitochondrial gene expression in Saccharomyces cerevisiae is responsible for the
      production of highly hydrophobic subunits of the oxidative phosphorylation
      system. Membrane insertion occurs cotranslationally on membrane-bound
      mitochondrial ribosomes. Here, by employing a systematic mass spectrometry-based
      approach, we discovered the previously uncharacterized membrane protein Mrx15
      that interacts via a soluble C-terminal domain with the large ribosomal subunit.
      Mrx15 contacts mitochondrial translation products during their synthesis and
      plays, together with the ribosome receptor Mba1, an overlapping role in
      cotranslational protein insertion. Taken together, our data reveal how these
      ribosome receptors organize membrane protein biogenesis in mitochondria.

PMID- 30091673
TI  - Endoplasmic reticulum-associated degradation and disposal of misfolded GPI
      anchored proteins in Trypanosoma brucei.
AB  - Misfolded secretory proteins are retained by endoplasmic reticulum quality
      control (ERQC) and degraded in the proteasome by ER-associated degradation
      (ERAD). However, in yeast and mammals, misfolded glycosylphosphatidylinositol
      (GPI)-anchored proteins are preferentially degraded in the vacuole/lysosome. We
      investigate this process in the divergent eukaryotic pathogen Trypanosoma brucei
      using a misfolded GPI-anchored subunit (HA:E6) of the trypanosome transferrin
      receptor. HA:E6 is N-glycosylated and GPI-anchored and accumulates in the ER as
      aggregates. Treatment with MG132, a proteasome inhibitor, generates a smaller
      protected polypeptide (HA:E6*), consistent with turnover in the proteasome.
      HA:E6* partitions between membrane and cytosol fractions, and both pools are
      proteinase K-sensitive, indicating cytosolic disposition of membrane-associated
      HA:E6*. HA:E6* is de-N-glycosylated and has a full GPI-glycan structure from
      which dimyristoylglycerol has been removed, indicating that complete GPI removal
      is not a prerequisite for proteasomal degradation. However, HA:E6* is apparently
      not ubiquitin-modified. The trypanosome GPI anchor is a forward trafficking
      signal; thus the dynamic tension between ERQC and ER exit favors degradation by
      ERAD. These results differ markedly from the standard eukaryotic model systems
      and may indicate an evolutionary advantage related to pathogenesis.

PMID- 30091674
TI  - Disseminated leptomeningeal tumour mimicking a subarachnoid haemorrhage.
AB  - This article describes an unusual presentation of disseminated oligodendroglial
      like leptomeningeal tumour. A previously healthy 23-year-old Caucasian woman
      presented with headache, photophobia and recurrent seizures. Initial
      investigations were suggestive of subarachnoid haemorrhage. Her symptoms
      deteriorated rapidly and within weeks she developed complete blindness and
      diffuse sensory ataxia. The aim of this article is to increase awareness of this
      rare disease, especially in patients who present with acute, rapidly progressive
      neurological symptoms with signs of acute or chronic central nervous system
      bleeding.

PMID- 30091676
TI  - Phytohormone Abscisic Acid Protects Human Neuroblastoma SH-SY5Y Cells Against 6
      Hydroxydopamine-Induced Neurotoxicity Through Its Antioxidant and Antiapoptotic
      Properties.
AB  - Parkinson's disease (PD) is a destroying and prevalent neurodegenerative disease
      that is characterized by a progressive death of midbrain dopaminergic neurons. It
      is important to understand the possible neuroprotective effects of reagents that
      rescue the neurons from death and apoptosis. In this study, we investigated the
      effects of abscisic acid (ABA) on 6-hydroxydopamine (6-OHDA)-induced
      neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cell line as an in
      vitro model of PD. Cell damage was induced by 150 MUM 6-OHDA and the cell
      viability was examined by 2-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium
      bromide (MTT) assay. Reactive oxygen species (ROS) and mitochondrial membrane
      potential were assessed by fluorescence probe methods. Biochemical markers of
      apoptosis were also determined by immunoblotting. The data showed that 6-OHDA
      caused a significant loss of cell viability and mitochondrial membrane potential.
      In addition, intracellular ROS, cleaved caspase-3, Bax:Bcl-2 ratio, and
      cytochrome c release were significantly increased in 6-OHDA-incubated cells. ABA
      (100 MUM) elicited a significant protective effect and reduced biochemical
      markers of cell damage and death. Blockage of peroxisome proliferator-activated
      receptor (PPAR)gamma completely prevented the effect of ABA on 6-OHDA-induced
      cell toxicity. The results suggest that ABA has neuroprotective property against
      6-OHDA-induced neurotoxicity, which is performed through PPARgamma signaling.
      However, ABA antioxidant and antiapoptotic properties are involved, at least in
      part, in such protection.

PMID- 30091675
TI  - Evaluation of tissue computed tomography number changes and dosimetric shifts
      after conventional whole-breast irradiation in patients undergoing breast
      conserving surgery.
AB  - The aim of this study was to assess tissue computed tomography (CT) number
      changes and corresponding dosimetric shifts in repeatedly performed simulation CT
      (re-sim CT) scans after conventionally fractionated irradiation in breast cancer
      patients. A total of 28 breast cancer patients who underwent breast-conserving
      surgery were enrolled in this study. All the patients had received 50.4 Gy of
      conventional whole-breast irradiation (WBI) and underwent re-sim CT scans for
      tumor bed boost. For evaluation of dosimetric shifts between initial and re-sim
      CT scans, electron boost plans in the same field size with the same monitor unit
      with source-to-skin distance of 100 cm were conducted. Dosimetric parameters
      (V105%, V103%, V100%, V98%, V95%, V90%: Vx% indicates volumes which receive X% of
      prescribed doses) between initial and re-sim CT scans were compared. The CT
      number data (CTmean, CTmax, CTmin) of the original and irradiated CT (re-sim CT)
      scans from each representative structure (lung, rib bone, soft tissue, muscle,
      etc.) were examined and recruited. CT numbers showed highly variable changes.
      Soft tissue CTmean and muscle CTmax/CTmin showed statistically and significantly
      increased values in the CT (re-sim CT) compared to the original CT scans. Rib
      bone CTmean/CTmin showed statistically and significantly decreased values in the
      re-sim CT compared to the original CT scans. Other CT number values showed no
      statistically significant changes. Among the dosimetric parameters, only V105% (p
      = 0.015, mean = 3.07 cc versus 1.63 cc) and V103% (p = 0.017, mean = 13.8 cc
      versus 11.9 cc) exhibited statistically increased values in the re-sim CT
      compared to the original CT scans. CT number changes after conventional WBI were
      different according to tissue component. For electron boost plans, the
      implementation of a re-sim CT might be helpfully considered because significant
      dosimetric factor changes were observed especially in the high-dose areas (hot
      spots: V105% and V103%).

PMID- 30091677
TI  - Non-Invasive Pressure Reactivity Index Using Doppler Systolic Flow Parameters: A
      Pilot Analysis.
AB  - The goal was to predict pressure reactivity index (PRx) using non-invasive
      transcranial Doppler (TCD) based indices of cerebrovascular reactivity, systolic
      flow index (Sx_a), and mean flow index (Mx_a). Continuous extended duration time
      series recordings of middle cerebral artery cerebral blood flow velocity (CBFV)
      were obtained using robotic TCD in parallel with direct intracranial pressure
      (ICP). PRx, Sx_a, and Mx_a were derived from high frequency archived signals.
      Using time-series techniques, autoregressive integrative moving average (ARIMA)
      structure of PRx was determined and embedded in the following linear mixed
      effects (LME) models of PRx: PRx ~ Sx_a and PRx ~ Sx_a + Mx_a. Using 80% of the
      recorded patient data, the LME models were created and trained. Model superiority
      was assessed via Akaike information criterion (AIC), Bayesian information
      criterion (BIC), and log-likelihood (LL). The superior two models were then used
      to predict PRx using the remaining 20% of the signal data. Predicted and observed
      PRx were compared via Pearson correlation, linear models, and Bland-Altman (BA)
      analysis. Ten patients had 3-4 h of continuous uninterrupted ICP and TCD data and
      were used for this pilot analysis. Optimal ARIMA structure for PRx was determined
      to be (2,0,2), and this was embedded in all LME models. The top two LME models of
      PRx were determined to be: PRx ~ Sx_a and PRx ~ Sx_a + Mx_a. Estimated and
      observed PRx values from both models were strongly correlated (r > 0.9; p <
      0.0001 for both), with acceptable agreement on BA analysis. Predicted PRx using
      these two models was also moderately correlated with observed PRx, with
      acceptable agreement (r = 0.797, p = 0.006; r = 0.763, p = 0.011; respectively).
      With application of ARIMA and LME modeling, it is possible to predict PRx using
      non-invasive TCD measures. These are the first and as well as being preliminary
      attempts at doing so. Much further work is required.

PMID- 30091678
TI  - The kinetics of typical medical waste pyrolysis based on gaseous evolution
      behaviour in a micro-fluidised bed reactor.
AB  - In order to obtain the kinetic parameters during typical medical waste pyrolysis,
      the typical medical waste is pyrolysed in a micro-fluidised bed reactor. The
      gases evolved from the typical medical waste pyrolysis are analysed by a mass
      spectrometer, and only H2, CH4, C2H2, C2H4, C2H6, C3H6, C3H8 and C4H4 are
      observed. According to the gaseous product concentration profiles, the activation
      energies of gaseous formation are calculated based on the Friedman approach, and
      the average activation energies of H2, CH4, C2H2, C2H4, C2H6, C3H6, C3H8 and C4H4
      formation during typical medical waste pyrolysis are in sequence as 65.10, 39.98,
      35.17, 38.71, 40.75, 41.79, 58.57 and 63.95 kJ mol-1. Moreover, the activation
      energy with respect to the gases mixture formation is 52.70 kJ mol-1. Hence, it
      is concluded that the activation energy of typical medical waste pyrolysis is
      52.70 kJ mol-1. The model-fitting method is used to determine the mechanism model
      of medical waste pyrolysis. The results indicate that the chemical reaction ( n =
      1) model (G(x) = -ln(1-x)) is the optimum.

PMID- 30091680
TI  - Long-term monitoring to detect atrial fibrillation with the indwelling
      implantable cardiac monitors.
AB  - An increasing number of detection tools are available and several detection
      strategies have been described to pursue the diagnosis of atrial fibrillation to
      prevent ischemic stroke. Monitoring tools include standard electrocardiography,
      snapshot single-lead recordings with professional or personal devices (e.g.
      smartphone-based), Holter monitor, external devices with long-term recording
      capabilities, and cardiac implantable electronic devices, including pacemakers,
      implantable cardioverter defibrillators and insertable cardiac monitors.
      Insertable cardiac monitors have shown high sensitivity and specificity for the
      detection of atrial fibrillation, allow up to three years of continuous
      monitoring, do not require cooperation of the patient, are well tolerated, have a
      short device-related time delay between detection of atrial fibrillation and
      notification to the physician, provide information on atrial fibrillation burden
      and are minimally invasive. On the other hand, insertable cardiac monitors
      require a considerable use of resources to process the recordings and have a
      significant initial cost. Studies conducted with insertable cardiac monitors on
      patients with prior stroke and on patients with risk factors for stroke but no
      prior cerebrovascular events or atrial fibrillation have consistently shown a
      measurable incidence of atrial fibrillation at follow-up. However, the
      effectiveness of oral anticoagulations in reducing the incidence of ischemic
      stroke in patients with atrial fibrillation lasting less than 24 h, though
      reasonable, is currently unproven. The future of atrial fibrillation detection
      tools and atrial fibrillation detection strategies will be influenced by ongoing
      studies exploring whether oral anticoagulations reduce the incidence of stroke in
      patients with atrial fibrillation burden lower than 24 h.

PMID- 30091679
TI  - The 1-minute sit-to-stand test to detect exercise-induced oxygen desaturation in
      patients with interstitial lung disease.
AB  - BACKGROUND: Although the 6-min walk test (6MWT) is the gold standard for
      assessing exercise-induced impairment of gas exchange, it cannot easily be
      performed in a clinical office environment. The aim of this study was to compare
      the 1-min sit-to-stand test (1STST) with the 6MWT for the ability to assess
      exercise-induced oxygen desaturation in patients with interstitial lung diseases
      (ILDs). METHODS: A total of 107 patients were enrolled and classified into three
      groups: sarcoidosis, fibrotic idiopathic interstitial pneumonia (f-IIP), and
      other forms of ILD. The 6MWT and 1STST were performed on the same day, and
      pulmonary function tests, pulse oxygen saturation (SpO2), and dyspnea and fatigue
      (modified Borg scale) were assessed. SpO2 desaturation was evaluated by
      intraclass correlation coefficient (ICC), Bland-Altman analysis, and kappa
      (kappa) coefficient in the whole population and the patient subgroups. RESULTS:
      The SpO2 nadir during the 1STST and 6MWT showed good consistency [mean +/-
      standard deviation: 92.5% +/- 5% and 90% +/- 7%, respectively; ICC 0.77, 95%
      confidence interval (CI) 0.71-0.83] and correlated strongly ( r = 0.9, p <
      0.0001). The frequency of patients with oxygen desaturation ?4% was also
      consistent for the two exercise tests ( kappa = 0.68, 95% CI 0.54-0.82). The
      number of repetitions in the 1STST correlated with the 6MWT distance ( r = 0.5, p
      < 0.0001), but the dyspnea scores were higher during the 1STST than the 6MWT ( p
      < 0.0001). These findings did not differ for the three patient subgroups.
      CONCLUSION: The 1STST can measure exercise-induced desaturation in ILD patients
      and could be used as an alternative test to the 6MWT in office practice.

PMID- 30091682
TI  - Deoxynivalenol in wheat from the Northwestern region in China.
AB  - Because of global warming and changes in farming systems, Fusarium head blight
      has gradually spread towards high-latitude regions such as Northwestern China. A
      survey was conducted to assess the prevalence and concentration of deoxynivalenol
      (DON) in wheat harvested during 2013 from the Shaanxi, Ningxia, Gansu, and
      Xinjiang provinces in China. DON concentration in 181 wheat samples was analysed
      by high-performance liquid chromatography combined with ultraviolet detection. Of
      the wheat samples, 82.9% were contaminated with DON, with a mean DON
      concentration of 500 MUg/kg. According to the Chinese standard limits for DON,
      10% of the positive samples were above the maximum limit of 1000 MUg/kg. Regions
      with higher humidity showed higher levels of DON in the wheat samples. These
      results show the necessity of raising awareness of DON contamination in people
      from Northwestern China to protect their health from the risk of exposure to DON.

PMID- 30091681
TI  - Association of DFNA5, SYK, and NELL1 variants along with HPV infection in oral
      cancer among the prolonged tobacco-chewers.
AB  - Southeast Asia, especially India, is well known for the highest use of smokeless
      tobacco. These products are known to induce oral squamous cell carcinoma.
      However, not all long-term tobacco-chewers develop oral squamous cell carcinoma.
      In addition, germline variants play a crucial role in susceptibility, prognosis,
      development, and progression of the disease. These prompted us to study the
      genetic susceptibility to oral squamous cell carcinoma among the long-term
      tobacco-chewers. Here, we presented a retrospective study on prolonged tobacco
      chewers of Northeast India to identify the potential protective or risk
      associated germline variants in tobacco-related oral squamous cell carcinoma
      along with HPV infection. Targeted re-sequencing (n = 60) of 170 genetic regions
      from 75 genes was carried out in Ion-PGMTM and validation (n = 116) of the
      observed variants was done using Sequenom iPLEX MassARRAYTM platform followed by
      polymerase chain reaction-based HPV genotyping and p16-immunohistochemistry
      study. Subsequently, estimation of population structure, different statistical
      and in silico approaches were undertaken. We identified one nonsense-mediated
      mRNA decay transcript variant in the DFNA5 region (rs2237306), associated with
      Benzo(a)pyrene, as a protective factor (odds ratio = 0.33; p = 0.009) and four
      harmful (odds ratio > 2.5; p < 0.05) intronic variants, rs182361, rs290974, and
      rs169724 in SYK and rs1670661 in NELL1 region, involved in genetic susceptibility
      to tobacco- and HPV-mediated oral oncogenesis. Among the oral squamous cell
      carcinoma patients, 12.6% (11/87) were HPV positive, out of which 45.5% (5/11)
      were HPV16-infected, 27.3% (3/11) were HPV18-infected, and 27.3% (3/11) had an
      infection of both subtypes. Multifactor dimensionality reduction analysis showed
      that the interactions among HPV and NELL1 variant rs1670661 with age and gender
      augmented the risk of both non-tobacco- and tobacco-related oral squamous cell
      carcinoma, respectively. These suggest that HPV infection may be one of the
      important risk factors for oral squamous cell carcinoma in this population.
      Finally, we newly report a DFNA5 variant probably conferring protection via
      nonsense-mediated mRNA decay pathway against tobacco-related oral squamous cell
      carcinoma. Thus, the analytical approach used here can be useful in predicting
      the population-specific significant variants associated with oral squamous cell
      carcinoma in any heterogeneous population.

PMID- 30091684
TI  - Elimination of bovine viral diarrhoea virus in New Zealand: a review of research
      progress and future directions.
AB  - The major impacts of bovine viral diarrhoea (BVD) on cattle health and production
      have prompted many countries to embark on national elimination programmes. These
      programmes typically involve identifying and removing persistently infected (PI)
      cattle in infected herds and implementing biosecurity measures, such as pre- or
      post-movement testing. In order to design a systematic national control programme
      to eliminate BVD in New Zealand, which achieves the greatest benefits to the
      industries at the lowest cost to individual farmers, an accurate understanding is
      necessary of the epidemiology, economics and social motivation for BVD control in
      New Zealand. In this article we briefly review the pathogenesis of BVD,
      transmission and diagnosis of BVD virus infection, and effectiveness of
      vaccination. We summarise the current state of knowledge of the prevalence, risk
      factors for transmission, and financial impacts of BVD in New Zealand. We
      describe control programmes in Europe and then discuss the challenges that must
      be addressed to design a cost-effective national control programme to eliminate
      BVD in New Zealand.

PMID- 30091685
TI  - The Paradox of Viral Outrage.
AB  - Moral outrage has traditionally served a valuable social function, expressing
      group values and inhibiting deviant behavior, but the exponential dynamics of
      Internet postings make this expression of legitimate individual outrage appear
      excessive and unjust. The same individual outrage that would be praised in
      isolation is more likely to be viewed as bullying when echoed online by a
      multitude of similar responses, as it then seems to contribute to
      disproportionate group condemnation. Participants ( N = 3,377) saw racist,
      sexist, or unpatriotic posts with accompanying expressions of outrage and formed
      impressions of a single commenter. The same commenter was viewed more negatively
      when accompanied by a greater number of commenters (i.e., when outrage was viral
      vs. nonviral), and this was because viral outrage elicited greater sympathy
      toward the initial offender. We examined this effect and its underlying processes
      across six studies.

PMID- 30091683
TI  - miR-142-3p attenuates breast cancer stem cell characteristics and decreases
      radioresistance in vitro.
AB  - Effectively targeting cancer stem cells, a subpopulation of tumorigenic,
      aggressive, and radioresistant cells, holds therapeutic promise. However, the
      effects of the microRNA miR-142-3p, a small endogenous regulator of gene
      expression on breast cancer stem cells, have not been investigated. This study
      identifies the influence of miR-142-3p on mammary stemness properties and breast
      cancer radioresistance to establish its role in this setting. miR-142-3p
      precursor transfection was performed in MDA-MB-468, HCC1806, and MCF-7 cells, and
      stem cell markers CD44, CD133, ALDH1 activity and mammosphere formation were
      measured. beta-catenin, the canonical wnt signaling effector protein, was
      quantified by Western blots and cell fluorescence assays both in miR-142-3p
      overexpressing and anti-miR-142-3p-treated cells. Radiation response was
      investigated by colony formation assays. Levels of BRCA1, BRCA2, and Bod1 in miR
      142-3p-overexpressing cells as well as expression of miR-142-3p, Bod1, KLF4, and
      Oct4 in sorted CD44+/CD24-/low cells were determined by quantitative polymerase
      chain reaction. miR-142-3p overexpression resulted in a strong decline in breast
      cancer stem cell characteristics with a decrease in CD44, CD133, ALDH1, Bod1,
      BRCA2, and mammosphere formation as well as reduced survival after irradiation.
      miR-142-3p expression was strongly reduced in sorted CD44+/CD24-/low stem cells,
      while Bod1, Oct4, and KLF4 were overexpressed. beta-catenin levels strongly
      decreased after miR-142-3p overexpression, but not after anti-miR-142-3p
      treatment. We conclude that miR-142-3p downregulates cancer stem cell
      characteristics and radioresistance in breast cancer, mediated by a reduced role
      of beta-catenin in miR-142-3p-overexpressing cells. miR-142-3p might therefore
      help to target cancer stem cells.

PMID- 30091686
TI  - Data and Corporate Governance in Pharma and Digital Health: A Necessary
      Regulatory Convergence.
AB  - Data and Corporate Governance in Pharma and Digital Health: A Necessary
      Regulatory Convergence.

PMID- 30091687
TI  - Knockdown of p66Shc Alters Lineage-Associated Transcription Factor Expression in
      Mouse Blastocysts.
AB  - The p66Shc adaptor protein regulates apoptosis and senescence during early
      mammalian development. However, p66Shc expression during mouse preimplantation
      development is upregulated at the blastocyst stage. Our objective was to
      determine the biological function of p66Shc during mouse blastocyst development.
      In this study, we demonstrate that a reduced p66Shc transcript abundance
      following its short interfering RNA (siRNA)-mediated knockdown alters the
      spatiotemporal expression of cell lineage-associated transcription factors in the
      inner cell mass (ICM) of the mouse blastocyst. P66Shc knockdown blastocysts
      restrict OCT3/4 earlier to the inner cells of the early blastocyst and have ICMs
      containing significantly higher OCT3/4 levels, more GATA4-positive cells, and
      fewer NANOG-positive cells. P66Shc knockdown blastocysts also show a
      significantly reduced ability to form ICM-derived outgrowths when explanted in
      vitro. The increase in cells expressing primitive endoderm markers may be due to
      increased ERK1/2 activity, as it is reversed by ERK1/2 inhibition. These results
      suggest that p66Shc may regulate the relative abundance and timing of lineage
      associated transcription factor expression in the blastocyst ICM.

PMID- 30091688
TI  - Enhancing resiliency and promoting prosocial behavior among Tanzanian primary
      school students: A school-based intervention.
AB  - Children in Sub-Saharan Africa are living under chronic adversity due to poverty,
      serious health issues, physical and sexual abuse, and armed conflicts. These
      highly stressful conditions have deleterious effects on their mental health and
      socio-emotional adjustment. Since many children lack adequate access to mental
      health care, culturally adapted school-based resiliency programs could provide a
      resource to scaffold their development and promote their mental health. This
      study evaluated the efficacy of a universal school-based intervention in
      enhancing the resiliency of Tanzanian primary school children and cultivating
      prosocial behaviors. A total of 183 students from grades 4 to 6 were randomly
      assigned to either the 16-session "ERSAE-Stress-Prosocial (ESPS)" structured
      intervention or to a Social Study curriculum (SS) active control group. The
      original ESPS program was adapted by Tanzanians mental health professionals who
      modified the program based on local idioms of distress and indigenous practices.
      Students' resilience was evaluated before, after and 8 months following the
      intervention by assessing social difficulties, hyperactivity, somatization, level
      of anxiety, prosocial behaviors and school functioning as well as academic
      achievements and disciplinary problems. There was significant improvement on all
      outcome measures for the ESPS group compared to the control group post
      intervention and at the 8-month follow up. The ESPS intervention was equally
      effective on most measures for students experiencing different adversity levels.
      The results indicate that a culturally adapted universal school-based
      intervention can be effective in enhancing Tanzanian students' resiliency and
      promoting prosocial behaviors. Should these results be replicated and found
      enduring, the modified ESPS could be a valuable mental health-promoting
      intervention in other low-income countries.

PMID- 30091689
TI  - Migration, Identity, and Threatened Mental Health: Examples from Contemporary
      Fiction.
AB  - In 2015, the world saw 244 million international migrants. Migration has been
      shown to be both a protective and a risk factor for mental health, depending on
      circumstances. Furthermore, culture has an impact on perceptions and
      constructions of mental illness and identity, both of which can be challenged
      through migration. Using a qualitative research approach, we analysed five
      internationally acclaimed and influential novels and one theatre play that focus
      on aspects of identity, migration, and threatened mental health. As a mirror of
      society, fiction can help to understand perceptions of identity and mental
      suffering on an intrapsychic and societal level, while at the same time society
      itself can be influenced by works of fiction. Fiction is also increasingly used
      for didactic purposes in medical education. We found that the works of fiction
      discussed embrace a multifaceted biopsychosocial concept of mental illness.
      Constructs such as unstable premigration identity, visible minority status (in
      the host country) and identity confusion in second-generation migrants are
      conceptualised as risk factors for mental illness. Factors portrayed as
      protective comprised a stable premigration identity, being safe with a family
      member or good friend, (romantic) love, therapeutic writing, art, and the concept
      of time having an element of simultaneousness. This literature challenges the
      idiocentric model of identity. Analysing fictional texts on migration experiences
      can be a promising hypothesis-generating approach for further research.

PMID- 30091690
TI  - Beyond two worlds: Identity narratives and the aspirational futures of Alaska
      Native youth.
AB  - Indigenous communities across the Alaskan Arctic have experienced profound
      revisions of livelihood, culture, and autonomy over the past century of
      colonization, creating radical discontinuities between the lives of young people
      and those of their parents and Elders. The disrupted processes of identity
      development, access to livelihoods, and cross-generational mentorship associated
      with colonialism have created complex challenges for youth as they envision and
      enact viable paths forward in the context of a rapidly changing Arctic home. In
      this study, we consider the meanings associated with different constructions of
      culture and selfhood, and the ways in which these identity narratives position
      Inupiaq Alaskan Native youth in relation to their personal and collective
      futures. Through an intergenerational and participatory inquiry process, this
      study explores how representations of shared heritage, present-day struggles,
      resilience, and hope can expand possibilities for youth and thus impact
      individual and community health.

PMID- 30091691
TI  - Knowledge and attitudes about mental health among older immigrants from the
      former Soviet Union to Israel and their primary care physicians.
AB  - Previous studies have documented a high prevalence of psychological distress and
      mental illness among older immigrants from the former Soviet Union (FSU) in
      Israel. Yet, this population rarely seeks help from mental health providers. The
      present study aimed to identify beliefs and attitudes about depression and
      anxiety among older immigrants from the FSU treated in primary care, and among
      their primary care physicians, who were also FSU immigrants. The study used focus
      group (FG) interviews with primary care patients (n = 12) and physicians (n =
      23). The interviews were transcribed and analyzed using open thematic coding.
      Three main themes were identified: a) avoidance of discussion of mental health
      and stigma regarding mental illness; b) expectations to control one's mental
      state; and c) limited opportunities to acquire knowledge about Western mental
      health. Primary care physicians recognized the barriers facing their older
      immigrant patients concerning mental health diagnosis and treatment. Yet, due to
      work overload, their ability to assist older immigrants was limited. The findings
      suggest that older immigrants from the FSU might benefit from mental health
      information and exchange of ideas about Western mental health.

PMID- 30091692
TI  - Increased environmental sample area and recovery of Clostridium difficile spores
      from hospital surfaces by quantitative PCR and enrichment culture.
AB  - OBJECTIVE: Clostridium difficile spores play an important role in transmission
      and can survive in the environment for several months. Optimal methods for
      measuring environmental C. difficile are unknown. We sought to determine whether
      increased sample surface area improved detection of C. difficile from
      environmental samples. SETTING: Samples were collected from 12 patient rooms in a
      tertiary-care hospital in Toronto, Canada. METHODS: Samples represented small
      surface-area and large surface-area floor and bedrail pairs from single-bed rooms
      of patients with low (without prior antibiotics), medium (with prior
      antibiotics), and high (C. difficile infected) shedding risk. Presence of C.
      difficile in samples was measured using quantitative polymerase chain reaction
      (qPCR) with targets on the 16S rRNA and toxin B genes and using enrichment
      culture. RESULTS: Of the 48 samples, 64.6% were positive by 16S qPCR (geometric
      mean, 13.8 spores); 39.6% were positive by toxin B qPCR (geometric mean, 1.9
      spores); and 43.8% were positive by enrichment culture. By 16S qPCR, each 10-fold
      increase in sample surface area yielded 6.6 times (95% CI, 3.2-13) more spores.
      Floor surfaces yielded 27 times (95% CI, 4.9-181) more spores than bedrails, and
      rooms of C. difficile-positive patients yielded 11 times (95% CI, 0.55-164) more
      spores than those of patients without prior antibiotics. Toxin B qPCR and
      enrichment culture returned analogous findings. CONCLUSIONS: Clostridium
      difficile spores were identified in most floor and bedrail samples, and increased
      surface area improved detection. Future research aiming to understand the role of
      environmental C. difficile in transmission should prefer samples with large
      surface areas.

PMID- 30091693
TI  - Clinical outcome, healthcare cost and length of hospital stay among patients with
      bloodstream infections and acute leukemia in a cancer center in Eastern india -
      CORRIGENDUM.

PMID- 30091694
TI  - Primorskyibacter marinus sp. nov., isolated from coastal sediment.
AB  - A novel Gram-stain-negative, whitish-yellow, rod-shaped, non-pigmented, aerobic,
      oxidase-positive and catalase-positive bacterium, designated PX7T, was isolated
      from coastal sediment of Xiaoshi Island, Weihai, China (37 degrees  31' 36" N,
      122 degrees  00' 58" E). Strain PX7T grew optimally at 30  degrees C, at pH 7.0
      7.5 and in the presence of 3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S
      rRNA gene sequences revealed that strain PX7T formed a robust clade with members
      of the genus Primorskyibacter and was closely related to Primorskyibacter
      sedentarius, Primorskyibacter aestuariivivens and Primorskyibacter insulae with
      96.5, 96.2 and 95.1 % sequence similarities, respectively. The sole respiratory
      quinone of strain PX7T was ubiquinone-10, and the dominant fatty acid was C18 :
      1omega7c (80.2 %). The major polar lipids were phosphatidylglycerol,
      phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid, one
      unidentified phospholipid and one unidentified lipid. The DNA G+C content of
      strain PX7T was 60.2 mol%. Based on the combination of phylogenetic analyses,
      phenotypic and chemotaxonomic data, strain PX7T is considered to represent a
      novel species within the genus Primorskyibacter in the family Rhodobacteraceae,
      for which the name Primorskyibacter marinus sp. nov. is proposed. The type strain
      of the new species is PX7T (=KCTC 42952T=MCCC 1H00196T).

PMID- 30091695
TI  - Basal levels of (p)ppGpp differentially affect the pathogenesis of infective
      endocarditis in Enterococcus faecalis.
AB  - The alarmone (p)ppGpp mediates the stringent response and has a recognized role
      in bacterial virulence. We previously reported a stringent response-like state in
      Enterococcus faecalis isolated from a rabbit foreign body abscess model and
      showed that E. faecalis mutants with varying levels of cellular (p)ppGpp
      [Deltarel, DeltarelQ and the (p)ppGpp0 DeltarelDeltarelQ] had differential
      abilities to persist within abscesses. In this study, we investigated whether
      (p)ppGpp contributes to the pathogenesis of E. faecalis infective endocarditis
      (IE), a biofilm infection of the heart valves. While the stringent response was
      not activated in heart valve-associated E. faecalis, deletion of the gene
      encoding the bifunctional (p)ppGpp synthetase/hydrolase Rel significantly
      impaired valve colonization. These results indicate that the presence of (p)ppGpp
      is dispensable for E. faecalis to cause IE, whereas the ability to regulate
      (p)ppGpp levels is critical for valve colonization. Next, we characterized how
      basal (p)ppGpp levels affect processes associated with IE pathogenesis. Despite
      being defective in binding to BSA-coated polystyrene surfaces, the Deltarel
      strain bound to collagen- and fibronectin-coated surfaces and ex vivo porcine
      heart valves as well as the parent and DeltarelDeltarelQ strains, ruling out the
      possibility that the impaired IE phenotype was due to an attachment defect.
      Moreover, differences in cellular (p)ppGpp levels did not affect extracellular
      gelatinase activity but significantly impaired enterococcal invasion of human
      coronary artery endothelial cells. Taken together, this study uncovers for the
      first time the fact that differences in basal (p)ppGpp levels, rather than the
      stringent response, differentially affect processes that contribute to the
      pathogenesis of IE.

PMID- 30091696
TI  - Actinomadura deserti sp. nov., isolated from desert soil.
AB  - A Gram-positive, strictly aerobic actinobacterium, designated BMP B8004T, was
      isolated from desert soil collected in Xinjiang Province, Northwest China. It
      produced an extensively branched non-fragmenting substrate mycelium, and very
      scanty aerial mycelium that formed a short hooked chain of arthrospores with a
      smooth surface. Optimum growth occurred at 28  degrees C, pH 7.0 and 0 % (w/v)
      NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain
      BMP B8004T formed a distinct phyletic lineage within the genus Actinomadura. It
      shared the highest 16S rRNA gene sequence similarity to Actinomadura apis IM17-1T
      (99.2 %) and Actinomadura rifamycini NBRC 14183T (98.6 %). However, it could be
      distinguished from the two closest strains based on the low levels of DNA-DNA
      relatedness (52.7+/-0.7 and 45+/-1.8 %, respectively). Chemotaxonomic
      characteristics, including the main phospholipids, diphosphatidylglycerol,
      phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides,
      the major menaquinones MK-9(H6) and MK-9(H8), the predominant fatty acids iso-C16
      : 0, C16 : 0, C18 : 0 10-methyl and C18 : 1omega9c, were also consistent with the
      properties of the genus Actinomadura. The DNA G+C content of strain BMP B8004T
      was 71.9 mol%. Based on phenotypic and genotypic features, strain BMP B8004T is
      considered to represent a novel species of the genus Actinomadura, for which the
      name Actinomadura deserti sp. nov. is proposed. The type strain is BMP B8004T
      (=CGMCC 4.7432T=KCTC 39998T).

PMID- 30091697
TI  - ICTV Virus Taxonomy Profile: Globuloviridae.
AB  - The family Globuloviridae comprises enveloped viruses with linear, double
      stranded DNA genomes of about 21-28 kbp. The virions are spherical with a
      diameter of 70-100 nm. No information is available about genome replication.
      Globuloviruses infect hyperthermophilic archaea belonging to the genera
      Pyrobaculum and Thermoproteus, which thrive in extreme geothermal environments.
      Infection does not cause lysis of host cells and is noncytocidal. The viral
      genome does not integrate into the host chromosome. This is a summary of the
      International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of
      the Globuloviridae, which is available at www.ictv.global/report/globuloviridae.

PMID- 30091698
TI  - Virus innexin expression in insect cells disrupts cell membrane potential and pH.
AB  - Certain parasitoid wasps are associated with Polydnaviruses, symbiotic viruses
      that encode virulence factors which are essential to successful parasitization by
      the wasp of a caterpillar host. Members of one group of Polydnaviruses, the
      Ichnoviruses, encode a multi-gene family known as Vinnexins. Vinnexins are
      homologues of insect gap junction genes, and form functional gap junctions that
      may affect host cell physiology. However, the role of Vinnexins in host pathology
      and the mechanism by which these affect their caterpillar host are largely
      unknown. In this article, we generated recombinant baculoviruses to express
      vinnexins in Spodoptera frugiperda (Sf9) cells. To measure cell physiological
      changes caused by Vinnexins, cells were probed with a membrane potential
      sensitive probe, DiBac4(3), and a pH indicator, carboxyfluorescein diacetate
      (CFDA). In addition, we utilized carbenoxolone and ouabain, respectively, to
      probe the role of gap junctions and hemi-channels, and Na+/K+-ATPase in
      establishing membrane potential in studied cells. Our results indicate that
      Vinnexins induce cell membrane depolarization and cytoplasmic alkalization to a
      degree specific to each tested Vinnexin, and that neither Vinnexin hemi-channels
      nor Na+/K+-ATPase appear to underlie these effects directly. These results hint
      that members of the Vinnexin protein family may affect host bio-electrical
      phenomena to disrupt host cell physiology, and that the individual proteins of
      the family may differentially affect host physiology.

PMID- 30091699
TI  - Agaribacter flavus sp. nov., isolated from red algae.
AB  - A Gram-stain-negative, non-motile, aerobic, curved-rod bacterium, designated as
      strain 2p52T, was isolated from the marine algae Gracilaria blodgettii collected
      off the coast of Lingshui county, in Hainan province, China. Strain 2p52T grew at
      15-42  degrees C (optimally at 30-33  degrees C), at pH 6.0-10.0 (7.5-8.0) and in
      the presence of 1.0-8.0 % (w/v) NaCl (2.0-3.0 %). The most closely related
      species was Agaribacter marinus (96.5 % 16S rRNA gene sequence similarity).
      Phylogenetic analysis based on the sequence of the 16S rRNA gene revealed that
      strain 2p52T belonged to the genus Agaribacter. The novel strain contained
      phophatidylethanolamine and phosphatidylglycerol as the major polar lipids. The
      predominant isoprenoid quinine was Q-8, and the DNA G+C content was 43.2 mol%.
      The major cellular fatty acids were C16 : 1omega7c and/or iso-C15 : 0 2-OH, C16 :
      0, and C18 : 1omega7c. The phenotypic and systematic comparative analyses
      indicated that the isolate is representative of a novel species of the genus
      Agaribacter, and the name Agaribacter flavus sp. nov. is proposed. The type
      strain is 2p52T (=KCTC 52473T=MCCC 1H00151T).

PMID- 30091700
TI  - A quantitative approach for analyzing the spatio-temporal distribution of 3D
      intracellular events in fluorescence microscopy.
AB  - Analysis of the spatial distribution of endomembrane trafficking is fundamental
      to understand the mechanisms controlling cellular dynamics, cell homeostasy, and
      cell interaction with its external environment in normal and pathological
      situations. We present a semi-parametric framework to quantitatively analyze and
      visualize the spatio-temporal distribution of intracellular events from different
      conditions. From the spatial coordinates of intracellular features such as
      segmented subcellular structures or vesicle trajectories, QuantEv automatically
      estimates weighted densities that are easy to interpret and performs a
      comprehensive statistical analysis from distribution distances. We apply this
      approach to study the spatio-temporal distribution of moving Rab6 fluorescently
      labeled membranes with respect to their direction of movement in crossbow- and
      disk-shaped cells. We also investigate the position of the generating hub of
      Rab11-positive membranes and the effect of actin disruption on Rab11 trafficking
      in coordination with cell shape.

PMID- 30091701
TI  - Targeting light-gated chloride channels to neuronal somatodendritic domain
      reduces their excitatory effect in the axon.
AB  - Light-gated chloride channels are emerging as promising optogenetic tools for
      inhibition of neural activity. However, their effects depend on the transmembrane
      chloride electrochemical gradient and may be complex due to the heterogeneity of
      this gradient in different developmental stages, neuronal types, and subcellular
      compartments. Here we characterized a light-gated chloride channel, GtACR2, in
      mouse cortical neurons. We found that GtACR2 activation inhibited the soma, but
      unexpectedly depolarized the presynaptic terminals resulting in neurotransmitter
      release. Other light-gated chloride channels had similar effects. Reducing the
      chloride concentrations in the axon and presynaptic terminals diminished the
      GtACR2-induced neurotransmitter release, indicating an excitatory effect of
      chloride channels in these compartments. A novel hybrid somatodendritic targeting
      motif reduced the GtACR2-induced neurotransmitter release while enhancing the
      somatic photocurrents. Our results highlight the necessity of precisely
      determining the effects of light-gated chloride channels under specific
      experimental conditions and provide a much-improved light-gated chloride channel
      for optogenetic inhibition.

PMID- 30091702
TI  - VivosX, a disulfide crosslinking method to capture site-specific, protein-protein
      interactions in yeast and human cells.
AB  - VivosX is an in vivo disulfide crosslinking approach that utilizes a pair of
      strategically positioned cysteines on two proteins to probe physical interactions
      within cells. Histone H2A.Z, which often replaces one or both copies of H2A in
      nucleosomes downstream of promoters, was used to validate VivosX. Disulfide
      crosslinks between cysteine-modified H2A.Z and/or H2A histones within nucleosomes
      were induced using a membrane-permeable oxidant. VivosX detected different
      combinations of H2A.Z and H2A within nucleosomes in yeast cells. This assay
      correctly reported the change in global H2A.Z occupancy previously observed when
      the deposition and eviction pathways of H2A.Z were perturbed. Homotypic
      H2A.Z/H2A.Z (ZZ) nucleosomes accumulated when assembly of the transcription
      preinitiation complex was blocked, revealing that the transcription machinery
      preferentially disassembles ZZ nucleosomes. VivosX works in human cells and
      distinguishes ZZ nucleosomes with one or two ubiquitin moieties, demonstrating
      that it can be used to detect protein-protein interactions inside cells from
      different species.

PMID- 30091703
TI  - A discriminator code-based DTD surveillance ensures faithful glycine delivery for
      protein biosynthesis in bacteria.
AB  - D-aminoacyl-tRNA deacylase (DTD) acts on achiral glycine, in addition to D-amino
      acids, attached to tRNA. We have recently shown that this activity enables DTD to
      clear non-cognate Gly-tRNAAla with 1000-fold higher efficiency than its activity
      on Gly-tRNAGly, indicating tRNA-based modulation of DTD (Pawar et al., 2017).
      Here, we show that tRNA's discriminator base predominantly accounts for this
      activity difference and is the key to selection by DTD. Accordingly, the uracil
      discriminator base, serving as a negative determinant, prevents Gly-tRNAGly
      misediting by DTD and this protection is augmented by EF-Tu. Intriguingly,
      eukaryotic DTD has inverted discriminator base specificity and uses only G3*U70
      for tRNAGly/Ala discrimination. Moreover, DTD prevents alanine-to-glycine
      misincorporation in proteins rather than only recycling mischarged tRNAAla.
      Overall, the study reveals the unique co-evolution of DTD and discriminator base,
      and suggests DTD's strong selection pressure on bacterial tRNAGlys to retain a
      pyrimidine discriminator code.

PMID- 30091704
TI  - Strong biomechanical relationships bias the tempo and mode of morphological
      evolution.
AB  - The influence of biomechanics on the tempo and mode of morphological evolution is
      unresolved, yet is fundamental to organismal diversification. Across multiple
      four-bar linkage systems in animals, we discovered that rapid morphological
      evolution (tempo) is associated with mechanical sensitivity (strong correlation
      between a mechanical system's output and one or more of its components).
      Mechanical sensitivity is explained by size: the smallest link(s) are
      disproportionately affected by length changes and most strongly influence
      mechanical output. Rate of evolutionary change (tempo) is greatest in the
      smallest links and trait shifts across phylogeny (mode) occur exclusively via the
      influential, small links. Our findings illuminate the paradigms of many-to-one
      mapping, mechanical sensitivity, and constraints: tempo and mode are dominated by
      strong correlations that exemplify mechanical sensitivity, even in linkage
      systems known for exhibiting many-to-one mapping. Amidst myriad influences,
      mechanical sensitivity imparts distinct, predictable footprints on morphological
      diversity.

PMID- 30091706
TI  - Age-dependent dormant resident progenitors are stimulated by injury to regenerate
      Purkinje neurons.
AB  - Outside of the neurogenic niches of the brain, postmitotic neurons have not been
      found to undergo efficient regeneration. We demonstrate that mouse Purkinje cells
      (PCs), which are born at midgestation and are crucial for development and
      function of cerebellar circuits, are rapidly and fully regenerated following
      their ablation at birth. New PCs are produced from immature FOXP2+ Purkinje cell
      precursors (iPCs) that are able to enter the cell cycle and support normal
      cerebellum development. The number of iPCs and their regenerative capacity,
      however, diminish soon after birth and consequently PCs are poorly replenished
      when ablated at postnatal day five. Nevertheless, the PC-depleted cerebella reach
      a normal size by increasing cell size, but scaling of neuron types is disrupted
      and cerebellar function is impaired. Our findings provide a new paradigm in the
      field of neuron regeneration by identifying a population of immature neurons that
      buffers against perinatal brain injury in a stage-dependent process.

PMID- 30091705
TI  - An expanded toolkit for gene tagging based on MiMIC and scarless CRISPR tagging
      in Drosophila.
AB  - We generated two new genetic tools to efficiently tag genes in Drosophila. The
      first, Double Header (DH) utilizes intronic MiMIC/CRIMIC insertions to generate
      artificial exons for GFP mediated protein trapping or T2A-GAL4 gene trapping in
      vivo based on Cre recombinase to avoid embryo injections. DH significantly
      increases integration efficiency compared to previous strategies and faithfully
      reports the expression pattern of genes and proteins. The second technique
      targets genes lacking coding introns using a two-step cassette exchange. First,
      we replace the endogenous gene with an excisable compact dominant marker using
      CRISPR making a null allele. Second, the insertion is replaced with a
      protein::tag cassette. This sequential manipulation allows the generation of
      numerous tagged alleles or insertion of other DNA fragments that facilitates
      multiple downstream applications. Both techniques allow precise gene manipulation
      and facilitate detection of gene expression, protein localization and assessment
      of protein function, as well as numerous other applications.

PMID- 30091707
TI  - Clinical impact of collateral circulation in patients with median arcuate
      ligament syndrome.
AB  - PURPOSE: We aimed to analyze computed tomography (CT) findings and medical
      records of patients diagnosed with median arcuate ligament syndrome (MALS) and
      evaluate possible risk factors associated with vascular complications that
      develop in patients with MALS. METHODS: This retrospective study was approved by
      the institutional review board, and the requirement to obtain informed consent
      was waived. A total of 37 consecutive patients were diagnosed with MALS using
      both axial and sagittal CT reconstruction imaging at a single institution over a
      7-year period. Dynamic contrast-enhanced CT data, medical records, and
      angiography results were reviewed. RESULTS: Thirty-two (86.5%) patients were
      asymptomatic and incidentally diagnosed with MALS using CT. Seventeen (45.9%)
      patients exhibited significant arterial collateral circulations and nine (24.3%)
      were found to have splanchnic artery aneurysms, including one (2.7%) with acute
      bleeding secondary to aneurysm rupture. Peripancreatic vascular network including
      pancreaticoduodenal arcades and dorsal pancreatic artery was the most common site
      for development of both collateral circulations (16/22, 72.7%) and aneurysms
      (9/16, 56.3%). Splanchnic artery aneurysms were significantly more common in
      patients with collateral circulations (8/17, 47.1%) compared with those without
      collateral circulations (1/20, 5%) (P < 0.01). At least one peripancreatic
      vascular aneurysm was found in five of nine patients with splanchnic artery
      aneurysms (55.6%). CONCLUSION: Splanchnic artery aneurysms are not uncommon in
      asymptomatic patients with collateral circulations caused by significant celiac
      trunk stenosis or obstruction due to median arcuate ligament. Therefore, careful
      imaging evaluation is necessary in patients with peripancreatic collateral
      circulations associated with MALS and regular follow-up is recommended for
      possibility of aneurysm development and rupture. Prophylactic endovascular
      treatment should be specifically performed in patients with pancreaticoduodenal
      arcade aneurysms to prevent life-threatening aneurysm rupture regardless of size.

PMID- 30091708
TI  - US and MRI in the evaluation of mammographic BI-RADS 4 and 5 microcalcifications.
AB  - PURPOSE: The aim of this study was to assess diagnostic accuracies of
      ultrasonography (US) and magnetic resonance imaging (MRI) in lesions that
      manifest as mammographic BI-RADS 4 and 5 microcalcifications, in the setting of
      conjoined use of mammography, US, and MRI. METHODS: Patients with mammographic BI
      RADS 4 or 5 microcalcifications, without additional findings, were included in
      this prospective study. All patients subsequently underwent breast US and MRI.
      Histopathologic diagnosis, obtained by US-guided core-needle biopsy or surgical
      excision, served as a reference standard. Diagnostic accuracies of US and MRI
      were calculated, and positive predictive value for different MRI BI-RADS imaging
      features were determined. RESULTS: The study group consisted of 113 women with
      125 areas of suspicious microcalcifications. MRI reached sensitivity,
      specificity, positive predictive value 3 (PPV3), and negative predictive value
      (NPV) of 100%, 70.1%, 67.6%, and 100%, respectively. Statistically significant
      differences in MRI morphologic features and kinetic enhancement curves were
      observed between malignant and benign microcalcifications. Sensitivity,
      specificity, PPV3, and NPV for US were: 85.4%, 66.2%, 61.2%, and 87.9%. There was
      statistically significant difference in presentation of malignant and benign
      microcalcifications at US. CONCLUSION: In the setting of conjoined use of
      mammography, US, and MRI, MRI can reliably exclude malignancy in suspicious
      microcalcifications. Thus, negative MRI findings may influence the decision to
      biopsy the microcalcifications.

PMID- 30091709
TI  - Dynamic contrast-enhanced MRI for advanced esophageal cancer response assessment
      after concurrent chemoradiotherapy.
AB  - PURPOSE: We aimed to evaluate the treatment response of patients with esophageal
      cancer after concurrent chemoradiation therapy (CRT) using dynamic contrast
      enhanced magnetic resonance imaging (DCE-MRI). METHODS: This retrospective study
      included 59 patients with histologically confirmed esophageal squamous cell
      carcinoma. The patients underwent DCE-MRI before and 4 weeks after CRT. Patients
      with complete response were defined as the CR group; partial response, stable
      disease, and progressive disease patients were defined as the non-CR group. DCE
      MRI parameters (Ktrans, Ve, and Kep) were measured and compared between pre- and
      post-CRT in the CR and non-CR groups, respectively. Pre-CRT and post-CRT
      parameters were used to calculate the absolute change and the ratio of change.
      DCE-MRI parameters were compared between the CR and non-CR groups. Receiver
      operating characteristic (ROC) curves were used to verify diagnostic performance.
      RESULTS: Patients with higher T-stage esophageal cancer might present with poorer
      response. After CRT, the Ktrans and Kep values significantly decreased in the CR
      group, whereas only Kep value decreased in the non-CR group. The post-Ktrans and
      post-Kep values were observed to be significantly lower in the CR group than in
      the non-CR group. The absolute change and ratio of change of both Ktrans and Kep
      were higher in the CR group than in the non-CR group. Based on ROC analysis, the
      ratio of change in Ktrans was the best parameter to assess treatment response
      (AUC= 0.840). CONCLUSION: DCE-MRI parameters are valuable in predicting and
      assessing concurrent CRT response for advanced esophageal cancer.

PMID- 30091710
TI  - Imaging features of leadless cardiovascular devices.
AB  - Cardiovascular devices and hemodynamic monitoring systems continue to evolve with
      the goal of allowing for rapid clinical intervention and management.
      Cardiovascular devices including the CardioMicroelectromechanical (CardioMEMS)
      device, implantable loop recorder, and right ventricular (RV) leadless pacemaker
      are now widely used for treatment and monitoring of advanced cardiac conditions,
      as many of these devices have been shown to significantly improve patient
      outcomes. Additionally, hemodynamic monitoring devices have shown utility in
      monitoring patients with aortic aneurysms after endovascular aortic repair (EVAR)
      for early detection of Type I and Type II endoleaks. There is limited published
      data regarding the imaging features of these devices. As these devices become
      more widely used, it is important for radiologists to become familiar with the
      normal imaging features and potential complications. The goal of this review is
      to summarize the data regarding the use of leadless cardiovascular devices
      including the CardioMEMS device, implantable loop recorder, and RV leadless
      pacemaker, and to present cases demonstrating their utility and normal imaging
      features.

PMID- 30091711
TI  - A novel CT-guided technique using medical adhesive for localization of small
      pulmonary ground-glass nodules and mixed ground-glass nodules (<=20 mm) before
      video-assisted thoracoscopic surgery.
AB  - PURPOSE: We aimed to evaluate the success rate and complication occurrence of CT
      guided localization of small pure ground-glass nodules (pGGNs) and mixed ground
      glass nodules (mGGNs) with medical adhesive injection before video-assisted
      thoracoscopic surgery (VATS). METHODS: From March 2015 to May 2017, 41 patients
      with 44 small pGGNs and mGGNs underwent CT-guided percutaneous localization with
      medical adhesive prior to wedge resection by VATS. RESULTS: Localization with
      medical adhesive was successful in all patients (100%). The nodules (13 pGGNs, 31
      mGGNs) had a mean maximal long-axis diameter of 9+/-4 mm and a mean distance of
      10+/-7 mm from the most superficial edge of the nodule to the visceral pleura.
      The localization time was 16+/-8 minutes. There was a moderate inverse
      relationship between localization time and the nodule diameter (r= -0.42, P =
      0.005). Thirty-three nodules with primary lung cancer were pathologically
      confirmed. There were 3 cases of pneumothorax (7%), 3 cases of parenchyma
      hemorrhage (7%) and 2 cases of irritable cough (5%), respectively. No conversion
      to thoracotomy was necessary in any patient. CONCLUSION: CT-guided percutaneous
      localization with medical adhesive can label small pGGNs and mGGNs prior to VATS,
      with high success and low complication rates.

PMID- 30091712
TI  - Definitive locoregional therapy (LRT) versus bridging LRT and liver
      transplantation with wait-and-not-treat approach for very early stage
      hepatocellular carcinoma.
AB  - PURPOSE: Since the change in the United Network for Organ Sharing (UNOS) policy
      excluding patients with very early stage hepatocellular carcinoma (veHCC, single
      tumor nodule <2 cm) from receiving Model for End-stage Liver Disease (MELD)
      exception points, patients eligible to receive liver transplantation (LT) who
      fall in this category are commonly treated with locoregional therapy (LRT) after
      progression to UNOS T2 stage (1 nodule of 2-5 cm or up to 3 nodules, none above 3
      cm). The aim of the current study is to compare the outcomes of patients treated
      with bridging LRT and LT with wait-and-not-treat approach with patients treated
      with definitive LRT. METHODS: A retrospective study has been performed on
      patients with veHCC evaluated in multidisciplinary liver tumor clinic of a large
      academic center between 2004-2011. Patients eligible for LT were assigned to the
      wait-and-not-treat group while patients who were not eligible were assigned to
      the definitive LRT group. Tumor size, time to treatment, severity of liver
      disease, recurrence and survival from time of detection were reviewed and
      recorded. RESULTS: A total of 19 patients were identified and treated with
      definitive LRT while 57 patients were treated with bridging LRT prior to LT after
      disease progression to T2 stage. Patients in the definitive LRT group were older
      (70.4+/-10.2 years vs. 58.7+/-5.9 years, P < 0.001) and had more comorbid
      conditions compared with the wait-and-not-treat group. Mean survival for
      definitive LRT group at the end of 5 years was 34.3+/-6.0 months with a median of
      30.3 months (95% CI, 5.7-55.0 months) compared with 48.7+/-2.6 months for the
      wait-and-not-treat group, respectively (median not reached). The 3- and 5-year
      survival rates were 53.3% and 33.3% for the definitive LRT group compared with
      78.9% and 68.4% for the patients in the wait-and-not-treat group. Survival rate
      at the end of 5 years was significantly better for the wait-and-not-treat group
      (P = 0.013). CONCLUSION: Based on the findings of current retrospective study,
      treating veHCC (UNOS T1 stage) patients listed for LT with bridging LRT after
      disease progression to T2 stage appears to be safe and effective with high 5-year
      survival rates.

PMID- 30091714
TI  - Interstudy reproducibility of dark blood high-resolution MRI in evaluating
      basilar atherosclerotic plaque at 3 Tesla.
AB  - PURPOSE: We aimed to evaluate the interscan, intraobserver, and interobserver
      reproducibility of basilar atherosclerotic plaque employing dark blood high
      resolution magnetic resonance imaging (HR-MRI) at 3 Tesla. METHODS: Sixteen
      patients (14 males and 2 females) with > 30% basilar stenosis as identified by
      conventional magnetic resonance angiography were prospectively recruited for scan
      and rescan examinations on a 3 Tesla MRI system using T2-weighted turbo spin-echo
      protocol. Two observers independently measured the areas of vessels and lumens.
      Wall area was derived by subtracting the lumen area from the vessel area. Areas
      of vessels, lumens and walls were compared for the evaluation of interscan
      variability of basilar plaque. To assess the intraobserver variability, one
      observer reevaluated all the images of the first scan after a 4-week interval.
      RESULTS: Fourteen patients were included in the final analysis. No clinically
      significant difference was observed for interscan, intraobserver, and
      interobserver measurements. The intraclass correlations for vessel, lumen, and
      wall areas were excellent and ranged from 0.973 to 0.981 for the interscan
      measurements, 0.997 to 0.998 for the intraobserver measurements and 0.979 to
      0.985 for the interobserver measurements. The coefficients of variation for
      quantitative basilar morphology measurements were 4.31%-10.35% for the interscan
      measurements, 1.41%-4.62% for the intraobserver measurements and 3.79%-8.46% for
      the interobserver measurements. Compared with the interscan and interobserver
      measurements, narrow intervals of the scatterplots were observed for the
      intraobserver measurements by Bland-Altman plots. CONCLUSION: Basilar
      atherosclerotic plaque imaging demonstrates excellent reproducibility at 3 Tesla.
      The study proves that dark blood HR-MRI may serve as a reliable tool for clinical
      studies focused on the progression and treatment response of basilar
      atherosclerosis.

PMID- 30091715
TI  - Size-specific dose estimates in chest, abdomen, and pelvis CT examinations of
      pediatric patients.
AB  - PURPOSE: Size-specific dose estimates (SSDEs) are the latest focus of interest
      among medical physicists studying radiation dose to the patient in computed
      tomography (CT). This study aims to make conversions from CTDIvol to SSDE and
      investigate the relationship between mean SSDE (SSDE) and central SSDE
      (SSDEcenter) values for pediatric patients of different age groups undergoing
      chest, abdomen, and pelvis scans. METHODS: In this retrospective study, we
      examined 105 consecutive pediatric CT exams of chest, abdomen, and pelvis (CAP)
      classified in 3 separate groups according to age: 0-5 years, 6-10 years, and 11
      16 years. A MATLAB program was developed to determine SSDE values for each
      patient along 6 subregions: chest, abdomen, pelvis, chest and abdomen, abdomen
      and pelvis, and CAP. SSDE values derived over the slice at the center of each
      scan range (SSDEcenter) were also recorded. SSDE and corresponding SSDEcenter
      results were compared for each age group. RESULTS: Root mean square differences
      (RMSD) between SSDE and SSDEcenter values ranged between 0.13 mGy and 2.1 mGy
      through all groups and subregions, corresponding to 1.2% and 11%, respectively.
      CONCLUSION: In pediatric CT exams involving CAP region, CTDIvol and the water
      equivalent diameter at the middle of the scan range can be used to provide a
      reasonable estimate of mean SSDE with an RMSD of 11% at most.

PMID- 30091716
TI  - Predicting spirometry readings using cough sound features and regression.
AB  - OBJECTIVE: Spirometry is a commonly used method of measuring lung function. It is
      useful in the definitive diagnosis of diseases such as asthma and chronic
      obstructive pulmonary disease (COPD). However, spirometry requires cooperative
      patients, experienced staff, and repeated testing to ensure the consistency of
      measurements. There is discomfort associated with spirometry and some patients
      are not able to complete the test. In this paper, we investigate the possibility
      of using cough sound analysis for the prediction of spirometry measurements.
      APPROACH: Our approach is based on the premise that the mechanism of cough
      generation and the forced expiratory maneuver of spirometry share sufficient
      similarities enabling this prediction. Using an iPhone, we collected mostly
      voluntary cough sounds from 322 adults presenting to a respiratory function
      laboratory for pulmonary function testing. Subjects had the following diagnoses:
      obstructive, restrictive, or mixed pattern diseases, or were found to have no
      lung disease along with normal spirometry. The cough sounds were automatically
      segmented using the algorithm described in Sharan et al (2018 IEEE Trans. Biomed.
      Eng.). We then represented cough sounds with various cough sound descriptors and
      built linear and nonlinear regression models connecting them to spirometry
      parameters. Augmentation of cough features with subject demographic data is also
      experimented with. The dataset was divided into 272 training subjects and 50 test
      subjects for experimentation. MAIN RESULTS: The performance of the auto
      segmentation algorithm was evaluated on 49 randomly selected subjects from the
      overall dataset with a sensitivity and PPV of 84.95% and 98.51%, respectively.
      Our regression models achieved a root mean square error (and correlation
      coefficient) for standard spirometry parameters FEV1, FVC, and FEV1/FVC of 0.593L
      (0.810), 0.725L (0.749), and 0.164 (0.547), respectively, on the test dataset. In
      addition, we could achieve sensitivity, specificity, and accuracy of 70% or
      higher by applying the GOLD standard for COPD diagnosis on the estimated
      spirometry test results. SIGNIFICANCE: The experimental results show high
      positive correlation in predicting FEV1 and FVC and moderate positive correlation
      in predicting FEV1/FVC. The results show possibility of predicting spirometry
      results using cough sound analysis.

PMID- 30091713
TI  - Sonographically indeterminate scrotal masses: how MRI helps in characterization.
AB  - Magnetic resonance imaging (MRI) of the scrotum represents a useful supplemental
      imaging technique in the characterization of scrotal masses, particularly
      recommended in cases of nondiagnostic ultrasonographic findings. An accurate
      characterization of the benign nature of scrotal masses, including both
      intratesticular and paratesticular ones may improve patient management and
      decrease the number of unnecessary radical surgical procedures. Alternative
      treatment strategies, including follow-up, lesion biopsy, tumor enucleation, or
      organ sparing surgery may be recommended. The aim of this pictorial review is to
      present how MRI helps in the characterization of sonographically indeterminate
      scrotal masses and to emphasize the key MRI features of benign scrotal masses.

PMID- 30091717
TI  - Highly-sensitive gas sensor based on two-dimensional material field effect
      transistor.
AB  - Atomically thin two-dimensional (2D) materials are ideal gas sensing materials
      for achieving an ultra-low detection limit, due to the high surface-to-volume
      ratio, low electronic noise and sensitively tunable Fermi level. However, the
      sensitivity of 2D materials to their surrounding environment may also severely
      degrade the long-term stability of sensing devices, since most of them use the
      same 2D material flake as both the sensing and conduction material. In this work,
      we report a gas sensor based on a 2D material field effect transistor (FET) which
      uses few-layer black phosphorus (BP), boron nitride (BN) and molybdenum disulfide
      (MoS2) as the top-gate, dielectric layer and conduction channel, respectively. In
      this device configuration, the top-gate of BP with a superior gas adsorption
      capability serves as the sensing material, while the conduction channel of MoS2
      is isolated from ambient environment by the coverage of the BN dielectric layer.
      The separation of the sensing and conduction materials not only improves the long
      term stability of the device, but also enables us to use different materials for
      gas adsorption and conduction purposes to achieve optimum sensing performances.
      In addition, the adsorption kinetics of the gas molecules on the sensing channel
      can be sensitively detected by the current/resistance variation of the conduction
      channel, since the adsorbed gas molecules can effectively tune the Fermi level of
      sensing and conduction materials (BP and MoS2, respectively) through band
      alignment. We experimentally demonstrated that the proposed 2D material FET not
      only achieved a detection limit of 3.3 ppb to NO2, but was also capable to
      differentiate oxidizing and reducing gases.

PMID- 30091718
TI  - Age-related network topological difference based on the sleep ECG signal.
AB  - OBJECTIVE: Age has been shown to be a crucial factor for the EEG and fMRI small
      world networks during sleep. However, the characteristics of the age-related
      network based on the sleep ECG signal and how the network changes during
      different sleep stages are poorly understood. This study focuses on exploring the
      age-related scale-free and small-world network properties of the ECG signal from
      male subjects during distinct sleep stages, including the wakeful (W), light
      sleep (LS), deep sleep (DS) and rapid eye movement (REM) stages. APPROACH: The
      subjects are divided into two age groups: a younger (age  ?  40, n  =  11) group
      and an older group (age  >  40, n  =  25). MAIN RESULTS: For the scale-free
      network analysis, our results reveal a distinctive pattern of the scale free
      network topologies between the two age groups, including the mean degree
      ([Formula: see text]), the clustering coefficient ([Formula: see text]), and the
      path length ([Formula: see text]) features, such as the slope distribution of
      [Formula: see text] in the younger group increased from 1.99 during W to above
      2.05 during DS. In addition, the results indicate that the small-world properties
      can be found across all sleep stages in both age groups. However, the small-world
      index in the LS and REM stages significantly decreased with age (p  =  0.0006 and
      p  =  0.05, respectively). SIGNIFICANCE: The comparison analysis result indicates
      that the network topology variations in the sleep ECG signals are prone to show
      age-relevant differences that could be used for sleep stage classification and
      sleep disorder diagnosis.

PMID- 30091719
TI  - A general-threshold filtering method for improving intravoxel incoherent motion
      parameter estimates.
AB  - In this study, we present an image denoising method for diffusion-weighted
      magnetic resonance imaging (DW-MRI) data. Our aim is to improve the estimation of
      intravoxel incoherent motion (IVIM) parameters using denoised DW-MRI data. A
      general-threshold filtering (GTF) reconstruction via total variation minimization
      has been proposed to improve image quality in few-view computed tomography. Here,
      we applied the combination of GTF and total difference to image denoising. Voxel
      wise IVIM analysis was performed using both real and simulated DW-MRI data. Using
      an institutional review board-approved protocol with written informed consent, DW
      MRI imaging was performed at a 3 T hybrid PET/MR system in 10 patients with
      Hodgkin lymphoma lesions. A simulated phantom consisting of four organs (liver,
      pancreas, spleen and kidney) was used to generate noisy DW-MRI data according to
      the IVIM model at different noise levels. DW-MRI data were denoised before IVIM
      parameter estimation. The proposed image denoising method was compared with the
      image denoising method using joint rank and edge constraints (JREC). The results
      of simulated data show that at the lower signal-to-noise ratios the proposed
      image denoising method outperformed the JREC method in terms of the accuracy and
      precision of the IVIM parameter estimates. The experimental results also show
      that the proposed image denoising method could yield better parametric images
      than the JREC method in terms of noise reduction and edge preservation.

PMID- 30091720
TI  - Validation of x-ray fluorescence measurements of metals in toenail clippings
      against inductively coupled plasma mass spectrometry in a Nigerian population.
AB  - OBJECTIVE: Metal exposures have been linked with many adverse health outcomes
      affecting nearly every system in the body. Exposure to metals has been tracked
      primarily using blood. Blood metal concentrations have drawbacks as biomarkers
      stemming from the metals' short biologic half-lives, shipping and storage
      requirements, and invasive collection procedures. Toenails, which capture a
      longer exposure period, can be collected non-invasively and stored at room
      temperature, and can be more feasible and cost-effective for large-scale
      population studies. APPROACH: Inductively coupled plasma mass spectrometry (ICP
      MS) has been used for analysis of toenail metal concentrations, but x-ray
      fluorescence (XRF) has many advantages in versatility and cost effectiveness over
      these analyses. This study compared toenail concentrations of manganese (Mn) and
      lead (Pb) measured with XRF against ICP-MS, in samples collected from 20 adults
      in Nigeria. To do this we developed a novel calibration method that corrects XRF
      measurements for toenail weight and thickness to reduce the variability in XRF
      measurements of toenail clippings. MAIN RESULTS: We found a high correlation (R 
      =  0.91) between toenail manganese metal measurements made with XRF and ICP-MS
      and a correlation of (R  =  0.32) between toenail lead XRF and ICP-MS with over
      half of the lead results below the detection limit of the instrumentation.
      SIGNIFICANCE: XRF can be used effectively to quantify metals at the part per
      million level or lower depending on the XRF equipment used in the measurements.

PMID- 30091721
TI  - How does supercoiling regulation on a battery of RNA polymerases impact on
      bacterial transcription bursting?
AB  - Transcription plays an essential role in gene expression. The transcription
      bursting in bacteria has been suggested to be regulated by positive supercoiling
      accumulation in front of a transcribing RNA polymerase (RNAP) together with
      gyrase binding on DNA to release the supercoiling. In this work, we study the
      supercoiling regulation in the case of a battery of RNAPs working together on DNA
      by constructing a multi-state quantitative model, which allows gradual and
      stepwise supercoiling accumulation and release in the RNAP transcription. We
      solved for transcription characteristics under the multi-state bursting model for
      a single RNAP transcription, and then simulated for a battery of RNAPs on DNA
      with T7 and Escherichia coli RNAP types of traffic, respectively, probing both
      the average and fluctuation impacts of the supercoiling regulation. Our studies
      show that due to the supercoiling accumulation and release, the number of RNAP
      molecules loaded onto the DNA vary significantly along time in the traffic
      condition. Though multiple RNAPs in transcription promote the mRNA production,
      they also enhance the supercoiling accumulation to suppress the production. In
      particular, the fluctuations of the mRNA transcripts become highly pronounced for
      a battery of RNAPs transcribing together under the supercoiling regulation,
      especially for a long process of transcription elongation. In such an elongation
      process, though a single RNAP can work at a high duty ratio, multiple RNAPs are
      hardly able to do so. Our multi-state model thus provides a systematical
      characterization of the quantitative features of the bacterial transcription
      bursting; it also supports improved physical examinations on top of this general
      modeling framework.

PMID- 30091722
TI  - Focus on advances in electrical impedance tomography.

PMID- 30091723
TI  - Performance evaluation of the PET component of a hybrid PET/CT-ultrafast
      ultrasound imaging instrument.
AB  - We recently introduced a hybrid imaging instrument, PETRUS, based on a
      combination of positron emission tomography (PET) for molecular imaging, x-ray
      computed tomography (CT) for anatomical imaging, co-registration and attenuation
      correction, and ultrafast ultrasound imaging (UUI) for motion-correction,
      hemodynamic and biomechanical imaging. In order to ensure a precise co
      registration of simultaneous PET-UUI acquisitions, ultrasound probes attached to
      an ultrafast ultrasound scanner are operated in the field of view (FOV) of a
      small animal PET/CT scanner using a remote-controlled micro-positioner. Here we
      explore the effect of the presence of ultrasound probes on PET image quality. We
      compare the performance of PET and image quality with and without the presence of
      probes in the PET field of view, both in vitro following the NEMA-NU-4-2008
      standard protocol, and in vivo in small animals. Overall, deviations in the
      quality of images acquired with and without the ultrasound probes were under 10%
      and under 7% for the NEMA protocol and in vivo tests, respectively. Our results
      demonstrate the capability of the PETRUS device to acquire multimodal images in
      vivo without significant degradation of image quality.

PMID- 30091724
TI  - Impact of source doping on the performance of vertical InAs/InGaAsSb/GaSb
      nanowire tunneling field-effect transistors.
AB  - In this paper, we analyze experimental data from state-of-the-art vertical
      InAs/InGaAsSb/GaSb nanowire tunneling field-effect transistors (TFETs) to study
      the influence of source doping on their performance. Overall, the doping level
      impacts both the off-state and on-state performance of these devices. Separation
      of the doping from the heterostructure improved the subthreshold swing of the
      devices. The best devices reached a point subthreshold swing of 30 mV/dec at 100
      x higher currents than previous Si-based TFETs. However, separation of doping
      from the heterostructure had a significant impact on the on-state performance of
      these devices due to effects related to source depletion. An increase in the
      doping level helped to improve the on-state performance, which also increased the
      subthreshold swing. Thus, further optimization of doping incorporation with the
      heterostructure will help to improve vertical InAs/InGaAsSb/GaSb nanowire TFETs.

PMID- 30091726
TI  - Effect of Caffeine on Serum Tumour Necrosis Factor Alpha and Lactate
      Dehydrogenase in Wistar Rats Exposed to Cerebral Ischaemia-reperfusion Injury.
AB  - Caffeine is known to confer neuro-protection via A1 and A2A adenosine receptor
      antagonism in which adenosine neuro-modulates excitotoxic release of glutamate.
      Currently, it is unclear whether caffeine modulates inflammation in ischaemic
      stroke model. The present study examined effects of caffeine following ischaemia
      reperfusion injury on neuro-inflammatory tumour necrosis alpha (TNF-alpha),
      lactate dehydrogenase (LDH), as well as effect of caffeine against brain
      ischaemic damage on histology. Thirty three adult male Wistar rats (180-300 g)
      were used in this study. They were randomly divided into four groups (n=5 each):
      Group I (Control) that received neither the operation nor any treatment; Group II
      (Sham/Water) received a pseudo-ischaemic-reperfusion and 1ml water for injection;
      Group III (BCCO/Water) that received complete bilateral common carotid occlusion
      (BCCO) and 1ml water for injection; Group IV (BCCO/Caffeine) that received
      complete BCCO and caffeine solution intraperitoneally at a dose of 50% LD50 value
      (144mg/kg); and thirteen rats were used for LD50 assessment. Sensory and motor
      functions significantly (p<0.05) decreased in the rat following ischaemia
      reperfusion injury when compared to pre-injury state on Garcia neurological
      score. Caffeine reduced brain ischaemic injury and significantly reduced (p<0.05)
      TNF-alpha activity. While no significant effects (p>0.05) of caffeine was
      observed on LDH activity. This study has shown neuro-protective roles of caffeine
      against ischaemia-reperfusion damage to brain tissue, inflammatory TNF-alpha
      activity, but not on LDH activity.

PMID- 30091725
TI  - Circulating and intrahepatic antiviral B cells are defective in hepatitis B.
AB  - B cells are increasingly recognized as playing an important role in the ongoing
      control of hepatitis B virus (HBV). The development of antibodies against the
      viral surface antigen (HBV surface antigen [HBsAgs]) constitutes the hallmark of
      resolution of acute infection and is a therapeutic goal for functional cure of
      chronic HBV (CHB). We characterized B cells directly ex vivo from the blood and
      liver of patients with CHB to investigate constraints on their antiviral
      potential. Unexpectedly, we found that HBsAg-specific B cells persisted in the
      blood and liver of many patients with CHB and were enriched for T-bet, a
      signature of antiviral potential in B cells. However, purified, differentiated
      HBsAg-specific B cells from patients with CHB had defective antibody production,
      consistent with undetectable anti-HBs antibodies in vivo. HBsAg-specific and
      global B cells had an accumulation of CD21-CD27- atypical memory B cells (atMBC)
      with high expression of inhibitory receptors, including PD-1. These atMBC
      demonstrated altered signaling, homing, differentiation into antibody-producing
      cells, survival, and antiviral/proinflammatory cytokine production that could be
      partially rescued by PD-1 blockade. Analysis of B cells within healthy and HBV
      infected livers implicated the combination of this tolerogenic niche and HBV
      infection in driving PD-1hiatMBC and impairing B cell immunity.

PMID- 30091727
TI  - Heparin Enhances the Effects of Mesenchymal Stem Cell Transplantation in a Rabbit
      Model of Acute Myocardial Infarction.
AB  - Stem cell transplantation in combination with administration of bioactive
      compounds has shown promising resultsin treating myocardial infraction (MI). In
      the current study, we investigated the effect of combining mesenchymal stem
      cells(MSCs) transplantation with heparin into the infarcted heart rabbits. For
      this purpose, 35 male New Zealand white rabbitswere randomly divided into five
      groups: sham, MI, MI+ MSCs, MI+ heparin and MI+MSCs+ heparin. MI was induced by30
      min ligation of the left anterior descending coronary artery. The animals of MSCs
      and MSCs +heparin groups wereinjected cell culture containing MSCs
      intramyocardially into the infarct area. Functional parameters of the left
      ventricle byechocardiography, serum levels of VEGF by enzyme-linked immunosorbent
      assay, size of fibrotic area by Masson'strichrome staining, evaluation of
      morphology by Haematoxylin-Eosin and capillary density alkaline phosphatase
      stainingwere compared between groups. Ejection fraction, fractional shortening
      and levels of VEGF significantly improved in MSCsand MSCs + heparin group
      (P<0.05). The fibrotic area was significantly reduced (p=0.009) in MSC + heparin
      treated animalsin comparison with MSCs. Number of live cells and angiogenesis
      were increased significantly in MSCs + heparin groups incomparison with MSCs (p<
      0.05). Although injection of MSCs significantly restored normal function of
      fibrotic area, wefound that administration of heparin combined with MSCs to
      infarcted heart of animals could have better effects on LVfunctional parameters
      in fibrosis area and resulted in superior therapeutic outcome in enhancing
      neovascularization andimproving cardiac fibrosis.

PMID- 30091728
TI  - Effect of Chronic Caffeine Consumption on Cardiac Tissue Metabolism in the
      Rabbit.
AB  - Previous studies on the ability of caffeine to enhance endurance and boost
      performance have focused on theenergy substrates that are utilized by the
      skeletal muscle and the brain but nothing of such has been reported on
      cardiactissue. This study was designed to investigate the effect of caffeine on
      cardiac tissue metabolism in the rabbit. The study wascarried out on adult male
      New Zealand rabbits divided into 3 groups (n=5). Group I rabbits served as
      control and were given0.5ml/Kg of normal saline while group II and III rabbits
      were administered with 2mg/Kg and 6mg/kg of caffeine respectivelyfor 28 days.
      Blood samples were collected by retro orbital puncture for biochemical analysis.
      Animals were sacrificed bycervical dislocation and cardiac tissue biopsies were
      collected for biochemical and immunohistochemical analysis. Cardiactissue
      glycogen concentration was determined by anthrone reagent method. Cardiac tissue
      CPT 1 activity and cAMPconcentration were determined by immunohistochemistry and
      colorimetry techniques respectively, with assay kits obtainedfrom Biovision Inc.
      The results showed that Caffeine at 2 and 6 mg/kg significantly inhibited MPO
      activity from 0.72+/-0.05to 0.164+/-0.045 and 0.46+/-0.12 U/L respectively
      (p<0.05). Caffeine at 2mg/kg had no effect on serum nitric oxide but at6mg/Kg, it
      significantly increased serum nitric oxide form 28.01+/-6.53 to 45.25+/-3.88uM of
      nitrite (p<0.05). Also, Caffeineat 2 and 6mg/kg increased cardiac tissue glycogen
      from 15.62+/-0.73 to 40.69+/-6.35 and 38.82+/-6.91mg/100g respectively
      andcarnitine palmytol transferase 1 activity from 18.3 to 20 and 25.2%
      respectively. In conclusion, the study showed that caffeineconsumption increased
      CPT 1 activity suggesting increased utilization of free fatty acids for energy
      metabolism and sparingof cardiac tissue glycogen by mechanism(s) which probably
      involved blockade of A1 adenosine receptors and cAMPsignaling pathway.

PMID- 30091729
TI  - Ahaptoglobinaemia in a Nigerian Cohort.
AB  - Ahaptoglobinaemia have been indicated in blacks from West Africa. Owing to the
      clinical and biologicimportance of haptoglobin (hpt), this work explores the
      situation in a Nigerian cohort since there are no published values ofhaptoglobin
      levels of individuals in this locality. The study was aimed at determining the
      amount of haptoglobin in the bloodof normal healthy Nigerians. Haptoglobin was
      quantitatively estimated in one hundred and fifty-two apparently
      healthyindividuals using highly sensitive immunoassay technology. Blood grouping
      and haemoglobin genotype were assayed forall subjects to know if they influence
      haptoglobin levels. The association between haptoglobin and blood group was
      alsoestablished. Serum levels of haptoglobin among all subjects analyzed revealed
      a marked decrease in their haptoglobin levelswhen compared to other reference
      intervals. A further association between haptoglobin and gender did not reveal a
      statisticalsignificant relationship (p>0.05). However, there was a significant
      different when haptoglobin levels of different bloodgroups and haemoglobin
      genotype when compared. Our data suggest that serum levels of haptoglobin are
      significantly lowerin healthy Nigerians. The lower limit was remarkably lower
      than the internationally acceptable Caucasian reference rangesuggesting a clear
      necessity for establishing reference African values.

PMID- 30091730
TI  - Haemostatic Indices as Markers for Monitoring Pulmonary Tuberculosis Treatment.
AB  - Tuberculosis (TB) is an infectious disease inducing a state of chronic
      inflammation which could affect thehaemostatic mechanism as part of host defences
      against infection. Proper diagnosis and monitoring of tuberculosis
      patientsundergoing therapy is still a challenge especially in a poor resource
      country such as Nigeria. This study aims to assess somehaemostatic indices of
      tuberculosis patients and their possible use as markers in monitoring response to
      anti-tuberculosistreatment. One hundred and twenty TB patients aged 15-60 years
      and 120 apparently healthy (control) subjects age andgender-matched were studied.
      Demographic/bio data was compiled by interview and from patients' case notes.
      Diagnosis ofTB was by sputum smear microscopy, radiography and clinical
      assessment. Platelet count (PLT), platelet factor 4 (PF4),prothrombin time (PT),
      activated partial thromboplastin time (APTT), thrombin clotting time (TCT) and
      fibrinogen (FIB)were determined using standard techniques. The platelet factor 4,
      prothrombin time, activated partial thromboplastin timeand fibrinogen levels of
      TB patients were significantly higher while the thrombin clotting time was
      significantly lower(P<0.05) when compared with healthy subjects. While PF4, TCT
      and FIB improved significantly (P<0.05) as antituberculosis therapy progressed,
      PLT, PT and APTT remained the same. It is concluded that abnormal activation
      ofhaemostasis occurs in TB condition thus pre-disposing TB patients to bleeding
      complications. Furthermore, platelet factor4, thrombin clotting time and
      fibrinogen improved as therapy progressed and therefore may be used as markers
      for monitoringresponse to anti-tuberculosis therapy.

PMID- 30091731
TI  - Metabolic Fate of the Glucose Taken up by the Intestine During Induced
      Hyperglycaemia in Dogs.
AB  - Available data showed that the intestine increases it glucose uptake in response
      to hyperglycemia induced by anycause. However, what the intestine does with the
      glucose is not known. This study investigated the metabolic fate of theglucose
      taken up by the intestine during hyperglycaemia in dogs. Experiments were carried
      out on fasted, male, anaesthetizedmongrel dogs divided into 4 groups. The control
      (group 1, n=5) received normal saline (0.2 ml/kg) while groups 2-4(subdivided
      into two as low or high dose, n=5 each) received adrenaline (1 MUg/kg or 5
      MUg/kg), glucagon (3 ng/kg or 8 ng/kg)and glucose (10 mg/kg/min or 20 mg/kg/min).
      Through a midline laparatomy, the upper jejunum was cannulated for
      IntestinalBlood Flow (IBF) measurement. Blood glucose and lactate levels were
      determined using glucose oxidase and lactatedehydrogenase methods, respectively.
      Intestinal Glucose/Lactate Uptake (IGU/ILU) was calculated as the product of
      IBFand arterio-venous glucose /lactate difference [(A-V) glucose/lactate].
      Jejunal tissue samples were obtained for the determinationof Glycogen Content
      (GC) and activities of Glycogen Synthase (GS), Glycogen Phosphorylase 'a' (GPa),
      hexokinase andglucose-6-phosphatase. Anthrone method was used to determine GC
      while activities of GS, GPa, hexokinase and glucose-6-phosphatase were determined
      spectrophotometrically. Data were subjected to descriptive statistics and
      analyzed usingstudent's t-test and ANOVA at alpha0.05. Arterial and venous blood
      glucose and lactate were increased by adrenaline, glucagonand glucose. Venous
      lactate was higher than arterial lactate in all groups. Intestinal blood flow, (A
      V) glucose and (A-V)lactate were increased in all the experimental groups.
      Intestinal glucose uptake increased by 624% (adrenaline), 705%(glucagon) and 589%
      (glucose) while intestinal lactate release increased by 422%, 459% and 272%
      respectively. IntestinalGC increased from 138.72 +/- 4.58 mg/100 g to 167.17 +/-
      4.20 mg/100 g (adrenaline), 229.21 +/- 6.25 mg/100 g (glucagon) and165.17 +/-
      4.20 mg/100 g (glucose). Adrenaline and glucose had no effect on GS activity but
      it was increased by glucagon;GPa was decreased while hexokinase activity was
      increased by adrenaline, glucagon, and glucose. Glucose-6-phosphataseactivity was
      not affected by adrenaline and glucagon but decreased by glucose. The intestine
      modulates blood glucose levelsthrough lactate formation, glycogen formation and
      most probably conversion of lactate to glucose through gluconeogenesis.

PMID- 30091732
TI  - Serum Levels of Inflammatory Cytokines in Helminth Infested Pregnant Women and
      Cord Blood of their Babies in Relation to Pregnancy Outcome.
AB  - Pregnancy places a very high demand on physical, physiological and immunological
      responses of females,especially when aggravated by parasitic infestation. There
      is strong evidence that maternal infestations with helminth haveprofound effects
      on immunity to helminths and other pathogens. This case-control study involved
      245 pregnant women aged18-40 years (>30 weeks of gestation) recruited from three
      secondary level hospitals in Ibadan, Nigeria. Morning stoolsamples collected from
      pregnant women were examine for intestinal helminths using formol-ether
      concentration method. Atotal of 38 participants comprising 17 Helminth Positive
      (HP) and 21 Helminth Negative (HN) pregnant women werepurposely selected for the
      study. Sera from these women (38) and their babies' cord (38) were analysed for
      immune factors[interleukins 6 and 8 (IL-6, IL-8), tumor necrosis factor-alpha
      (TNF-alpha) and immunoglobulin E (IgE)] were analyzed usingELISA. Anthropometric
      indices [weight and height in mothers and babies and Chest Circumference (CC) in
      babies] weremeasured using standard methods. Data were subjected to descriptive
      statistics and analysed using Student t-test and Pearsoncorrelation at alpha0.05.
      Only Ascaris lumbricoides was found in the 17 (6.9%) infested pregnant women. The
      mean levels of IL-6 (57.8 +/- 32.8 vs 52.8+/-39.6 pg/mL), IL-8 (24.3+/-3.5 vs
      22.0+/-7.1 pg/mL) and IgE (333.3+/-96.6 vs 242.3+/-96.8 IU/mL) weresimilar in HP
      when compared with HN. In cord sera, IL-8 level was significantly higher in
      babies of HP (23.7+/-3.9 pg/mL)compared with babies of HN (20.1+/-5.9 pg/mL). The
      levels of IL-6, TNF-alpha and nutritional indices in HP had significantpositive
      correlation with corresponding levels in babies of HP mothers. Only CC was
      significantly lowered in babies of HPcompared with HN mothers. Other
      anthropometric indices were not significantly different. Therefore, this present
      studysuggests that helminth infestation may lead to strong Th2 immune responses
      as is reflected by the cytokine levels of mothersand babies as well as
      anthropometric measurements of babies of infested mothers. The outcomes of this
      study provide basisto deworm pregnant women during pregnancy.

PMID- 30091733
TI  - Spermatotoxicity and Testicular Pathology in Wistar Strain Rats fed Graded Levels
      of Pigeon Pea Diet.
AB  - Pigeon pea is an important grain legume in the tropics and subtropics and it is a
      valuable source of low-cost plantprotein for humans and animals, but it remains
      an underutilized legume. Effects of feeding graded levels of raw pigeon pea seed
      inclusion diets on testicular function in Wistar rats was investigated. Thirty
      male Wistar rats weighing between 120 and 160 g were assigned into six groups (A
      F) of 5 rats each.

PMID- 30091734
TI  - Undergraduate Students' Understanding of Physiology Subject, Opinions and
      Perception: The Case of Bayero University, Kano, Nigeria.
AB  - Human Physiology courses are compulsory in medical education but many students
      encounter challenges instudying them. This study investigates understandings,
      opinions and perceptions of students about physiology subject andthe challenges
      they encounter in their study. Two hundred and eighty (280) students were
      interviewed using structuredquestionnaire. The data were analyzed using IBM SPSS
      statistics 22. The mean age of the students was 22.8 +/- 4.1 years.Males
      constituted 174(62.1%), while females were 106 (37.9%). Majority of the
      respondents were in 300 level of study inthe university 178(63.6%) as of the time
      of conducting this research. Most of the participants 257(91.8%) claimed to
      havegood to excellent understanding of the physiology subjects. One hundred and
      nine (39.1%) alleged that academic staff hadunfriendly attitude like rushing
      lectures, commencing lectures late and fixing tests and other continuous
      assessment close toexaminations, and that lecturers have poor communication/
      teaching skills. Less than one-third (28.7%) believed that thesubjects have bulky
      course contents, and 56(20.1%) were of the opinion that the students' lack of
      seriousness or interest isamong the reasons for failing physiology courses. On
      binary logistic regression, being of female sex, and in 300 level ofstudy emerged
      as the independent predictors of the students' perception of physiology.
      Improving the pedagogy 102(36.4%),good attitude of staff towards students and
      teaching 73(26.1%), improving infrastructure and equipment 35(12.5%);
      andinstituting guidance and counseling unit for both staff and student 31(11.1%)
      were the ways suggested by the students forimproving performance in physiology
      subject. Most of the students had poor and negative perception about
      physiologysubjects (83.2%). Guidance and counseling for students, through the
      level coordinators and the mentor-mentee programshould be strengthened in all
      departments. Basic infrastructure and equipment, and teaching techniques should
      also beupgraded.

PMID- 30091735
TI  - Deteriorating Hemostatic Functions of Adult Female Wistar Rats Mediated by
      Activities of Non-Steroidal AntiInflammatory Drugs (NSAIDs) - Piroxicam and
      Vitamin E.
AB  - : The status of hemostatic parameters, are useful physiological markers of organ
      and tissue damage anddysfunction. This study investigated the effect of Piroxicam
      on some hemostatic parameters of albino Wistar rats. Twentyfour (24) female
      albino Wistar rats were used for this study, they were randomly divided into four
      (4) groups of six (6) ratseach. Group A served as control, Group B and C were
      rats treated with 0.1 mg/kg and 0.2 mg/kg piroxicam while Group Dserved as 0.2
      mg/kg piroxicam treated rats administered with Vitamin E. The experiment lasted
      for a period of 4 weeks, afterwhich the rats were euthanized. Blood sample was
      collected for measurement of bleeding time, clotting time, fibrinogenlevel and
      platelets count. One-way ANOVA was used to compare, means and a p<0.05 was
      considered significant. RESULT: Data generated showed that Piroxicam
      significantly (p<0.05) decreased the clotting time, platelets count and
      fibrinogen level.Piroxicam also significantly (p<0.05) increased the bleeding
      time level of the rats. Co-administration of Vitamin Esignificantly (p<0.05)
      increased the bleeding time, it also significantly decreased the clotting time,
      fibrinogen level andplatelets counts. CONCLUSION: This study therefore shows that
      Piroxicam impairs hemostasis while Vitamin E administrationfurther enhances the
      activities of Piroxicam on hemostatic parameters.

PMID- 30091736
TI  - Ameliorative Effects of Raffia hookeri Pulp Extract on Cisplatin-induced Brain
      Damage and Consequent Neurobehavioural Changes in Wistar Rats.
AB  - Cisplatin (CIS), a known anticancer drug, has side effects initiated by oxidative
      damage which hinders its use.Raffia hookeri pulp extract (RHPE), reported to
      possess antioxidant activity should mitigate cisplatin toxicity. The presentstudy
      examined the potential of RHPE to reduce brain damage in rats exposed to
      cisplatin. Forty eight female rats (150 g -220 g) were randomized into four
      groups (n = 12) viz: Group 1 served as control received distilled water daily,
      Group 2received 100 mg/kg body weight of RHPE, Group 3 received CIS (7.5 mg/kg
      body weight, intraperitoneally) as single dose,Group 4 received 100 mg/kg body
      weight of CIS+RHPE. The RHPE was given orally via gavage for 14 days while the
      singledose of cisplatin was administered on the eighth day of experiment.
      Behavioral tests namely: transitions, rearings, groomingsand forelimb grip
      strength were carried out on 15th day of the experiment after which rats were
      euthanized followed byhistology and histomorphometry. Cisplatin significantly
      (p<0.05) reduced the percentage body weight changes, transitions,rearings,
      groomings and forelimb grip strength compared with the control group, whereas
      treatment with CIS+RHPEsignificantly (p<0.05) increased these parameters compared
      with Cisplatin treatment. Cisplatin also caused histologicalalterations of
      Purkinje neurons, pyramidal neurons of Cornu ammonis3, granule cells and cerebral
      cortex neurons. Itsignificantly (p<0.05) reduced the diameter of Purkinje (9.1+/
      0.59 um) compared with control (14.41+/-0.31 um) andpyramidal neurons (11.32+/
      0.05 um) compared with control (17.03+/-0.54 um). Rats in the CIS+RHPE had their
      histologyconsiderably improved compared with those of cisplatin. In conclusion,
      RHPE reversed the behavioural changes anddemonstrated neuroprotection against CIS
      induced behavioural changes and microanatomical alterations of
      cerebellar,hippocampal and cerebral neurons.

PMID- 30091737
TI  - Dichlorvos Induced Oxidative and Neuronal Responses in Rats: Mitigative Efficacy
      of Nigella sativa (Black Cumin).
AB  - Poisoning from Organophosphates (OPs), especially Dichlorvos (DDVP) has become
      endemic due to theincreasing use in house hold and agricultural pests control,
      with most marked effects in the nervous system. However, it isevidenced that
      natural antioxidants are efficacious against OPs toxicity. Thus, this study
      investigated the possible antidotalefficacy of Nigella sativa oil (NSO) in
      Dichlovos (DDVP) induced oxidative and neuronal damages in Wistar rats. DDVPwas
      administered at sub-chronic daily dosage of 8.8 mg/kg.bw for 7 days and a post
      administration of NSO at 1 ml/kg.bwfor the subsequent 7 days. The rats were
      euthanized on the 15thday, blood sample collected via cardiac puncture,
      centrifugedand the plasma used for biochemical analysis of total antioxidant
      capacity (TAC), reduced glutathione (GSH) and totalreactive oxygen species (ROS),
      while the frontal, occipital and cerebellar cortices and the medulla were removed
      for histomorphological examinations. The results showed significant (P<=0.05)
      decrease in plasma TAC and GSH, while a significant(P<=0.05) increase in ROS was
      recorded, and some vacuolation around the neurons especially in the frontal and
      cerebellarcortices following DDVP exposure. However, post treatment with NSO was
      observed to be efficacious in the recovery ofthe oxidative activities and the
      neuro-architectural integrities. Thus, it can be concluded that the antioxidant
      capacity of NSOcould be efficacious against OPs induced oxidative damages,
      especially in dichlorvos accidents.

PMID- 30091738
TI  - Effects of Clove and Fermented Ginger on Blood Glucose, Leptin, Insulin and
      Insulin Receptor Levels in High Fat DietInduced Type 2 Diabetic Rabbits.
AB  - The aimed of this research is to evaluate the effects of clove and fermented
      ginger supplements on blood glucose,serum insulin, insulin receptor and Leptin
      levels of high fat diet-induced type 2 diabetes mellitus in rabbits. Clove and
      gingerare spices with records of medicinal value over decades. Thirty males
      rabbits weighing, 1-1.5kg were used for the research.Type 2 diabetes was induced
      by feeding the animals with a high fat diet for a period of eight weeks. Blood
      glucose levelswere determined after the induction period and rabbits having 140
      mg/dL and above were selected for the study. The animalswere grouped into six
      groups with five (n=5) rabbits in each group: Group 1 (Normoglycemic control
      group.) received normalfeed and distilled water ad libitum for six weeks; Group 2
      (Diabetic negative control group.) received normal feed anddistilled water ad
      libitum for six weeks; Groups 3 (Diabetic positive control.) received cholestran
      0.26g/kg and normal feedfor a period of six weeks; Group 4 and 5 (diabetic
      rabbits) were fed on 12.5%, clove and 12.5% fermented gingerrespectively for a
      period of six weeks; while Group 6 were co-fed on 12.5% clove and 12.5% fermented
      ginger for a periodof six weeks. Fasting blood glucose levels were determined at
      weekly interval during the treatment period. At the end of theexperiment, the
      rabbits were euthanized by cervical dislocation and blood samples were collected
      for the determination ofinsulin, insulin receptor and leptin levels. A
      significantly (P<0.05) decrease in blood glucose levels was recorded in
      thesupplements treated groups compared to diabetic control group. Clove
      supplement been most effective and sustaining inantihyperglycemic activity, also
      appears with a significant decreasing effect on leptin levels compared to
      diabetic controlgroup. A significant increase in insulin levels was also noted in
      the fermented ginger treated group along with higher levelsof Leptin compared as
      compared to control group. In conclusion the result of the study show that clove
      and fermented gingersupplementation possesses anti-diabetic properties and may
      help in the control of hyperleptinaemia in type 2 diabetes.

PMID- 30091739
TI  - Moringa oleifera Ameliorates Histomorphological Changes Associated with Cuprizone
      Neurotoxicity in the Hippocampal Cornu ammonis (CA) 3 Region.
AB  - Cuprizone-induced neurotoxicity has severally been used to study demyelinating
      diseases like multiple sclerosis(MS), adversely affecting both the white and grey
      matters of the brain. Lesions have been observed in different regions ofthe brain
      including, corpus callosum, neocortex and the hippocampal formation. The current
      study explored the role ofMoringa oleifera leaf extract in restoring the
      resultant histomorphological changes in cuprizone-induced hippocampaldamage in
      Wistar rats. Twenty adult female Wistar rats with average weight of 163.74 +/-
      3.59 g were grouped into A: Control,administered with 1 ml of normal saline, B:
      received 0.4% cuprizone diet, C: received 1.875 mg/ml/day of Moringa extract,and
      D: received a combination of cuprizone and Moringa in similar doses.
      Administration was oral for 5 weeks. The weightsof animals were assessed during
      treatment, and at the termination of experiment, the rats were euthanized and the
      brainswere fixed in 4% paraformaldehyde. The tissue was processed for
      histological and histochemical examinations using theHaematoxylin and Eosin stain
      and cresyl fast violet stain to assess the general microarchitecture and neuronal
      cellsrespectively of hippocampal cornu ammonis (CA) 3 region. The body weight of
      cuprizone-treated rats was reduced and thiswas ameliorated significantly in
      animals that were co-administered with Moringa. Similarly, there were
      histologicalalterations in the CA3 region of the hippocampus with the presence of
      pyknotic pyramidal cells organized in clusters andCA3 cells with degenerative
      changes, but administration of Moringa led to a better organised and fairly
      intact histologicalappearance. Pharmaceutical development of Moringa oleifera
      into appropriate therapeutic formulations could offer somerelief to patients of
      demyelinating conditions that have clinical features of neurological deficits.

PMID- 30091740
TI  - Changes in Ocular Perfusion Pressure in Response to Short Term Isometric Exercise
      in Young Adults.
AB  - Ocular Perfusion Pressure (OPP) is the pressure difference between the Mean
      Arterial Pressure (MAP) and theIntra Ocular Pressure (IOP). Decreased OPP could
      be a major risk factor for glaucoma. The aim is to study the effect ofIsometric
      exercise on OPP in apparently healthy young adults. Forty apparently healthy
      young adult volunteers comprising20 males and 20 females in the age group of 18
      21 years were selected among MBBS Phase I students of JSS Medicalcollege, JSSU,
      Mysore. IOP and BP were recorded. Mean arterial pressure (MAP) and OPP were
      calculated. There was astatistically significant difference (p<0.05) in the mean
      OPP before and after performing Isometric exercise and betweenmales (50.58+/-0.72
      to 56.85+/-1.15 mm Hg) and females (49.35 +/- 1.66 to 56.71 +/- 1.61 mm Hg).
      Physical activity in the formof Isometric exercise improves ocular blood flow -
      OPP. Hence regular exercise of prescribed intensity may prove useful
      forglaucomatous patients which enhance their OPP.

PMID- 30091741
TI  - Erythrocyte Sedimentation Rates and Leukogram Changes in Canine Model of
      Osteoarthritis.
AB  - Inflammatory markers such as erythrocyte sedimentation rates (ESR) have been
      evaluated in humans withosteoarthritis (OA). However, there has been no record of
      evaluation of ESR during OA in dogs. Changes in erythrocytesedimentation rates
      (ESR) and leukogram functions were evaluated following experimental knee
      osteoarthritis (OA).Tendogs of both sexes with (mean weight = 12.4 +/- 1.8kg)
      were used. Experimental OA was induced in the right knee, using thegroove model
      and confirmed radiographically using evidence of joint space narrowing and
      presence of osteophytes. Gaitwas assessed subjectively and scores (GAS) were
      assigned. Blood was obtained fortnightly for the determination of ESR,total white
      blood cell (tWBC), neutrophil and lymphocyte counts, while knee radiographs were
      obtained fortnightly fortwelve weeks. Radiographic scores (RAS), GAS, ESR and
      leukocyte parameters between the different time points werecompared with ANOVA.
      Correlation between parameters was evaluated using Pearson's correlation. A "P"
      value less than0.05 was considered significant. Both ESR and
      neutrophil/lymphocyte (N/L) ratio increased from week 0 to week 12 of OA.However,
      tWBC, neutrophil and lymphocyte counts did not differ significantly. Both GAS and
      RAS increased up to week 4and 6 of OA respectively. Erythrocyte sedimentation
      rates was significantly (p= 0.033) and positively correlated (r=0.793)with N/L
      ratio, but negatively and slightly correlated (r= -0.843) with GAS. There was no
      significant correlation betweenESR and RAS. It was concluded that both ESR and
      N/L ratio might be useful in monitoring progression of OA in dogs.

PMID- 30091742
TI  - Target discovery of ebselen with a biotinylated probe.
AB  - Despite numerous studies on ebselen over the past decade, its cellular targets
      remain obscure. Here we synthesized a biotinylated ebselen probe (biotin-ebselen)
      and characterized ebselen-binding proteins via an efficient activity-based
      protein profiling (ABPP) method, which allowed for the robust identification of
      462 targeted proteins in HeLa cells. This first work of global target profiling
      of ebselen will be helpful to re-design ebselen-based therapy appropriately in
      clinical trials.

PMID- 30091748
TI  - Pore size dependent cation adsorption in a nanoporous polymer film derived from a
      plastic columnar phase.
AB  - Self-supporting polymer thin films were obtained by the polymerization of an AB3
      type hydrogen-bonded complex in the plastic columnar phase. Porous polymers with
      pore diameters of ~1.1 and ~1.6 nm lined with either -COOH or -COONa groups were
      fabricated from the polymer thin films. Both the pore size and pore collapse
      influence the adsorption of cations.

PMID- 30091749
TI  - Autophagy is an important action mode for functionalized selenium nanoparticles
      to exhibit anti-colorectal cancer activity.
AB  - Selenium nanoparticles (SeNPs) have attracted much interest as potential
      anticancer nanodrugs. Our previous studies also demonstrated that SeNPs could be
      developed as carriers of clinically used anticancer drugs to achieve synergistic
      efficacy. Here, we describe the synthesis of Pleurotus tuber-regium (PTR)
      conjugated SeNPs (PTR-SeNPs) and their application in the treatment of colorectal
      cancer (CRC), which is one of the principal causes of cancer morbidity and
      mortality in the world. PTR-SeNPs were absorbed by cancer cells via clathrin
      mediated endocytosis into lysosomes and caveolae-mediated endocytosis into the
      Golgi apparatus. Internalized PTR-SeNPs trigger intracellular dose- and time
      dependent G2/M phase arrest and apoptosis. Moreover, as shown by using a pEGFP
      LC3 plasmid transfection model, PTR-SeNPs activate autophagy to promote the death
      of cancer cells via upregulation of beclin 1-related signaling pathways. In
      summary, this study demonstrates the high efficacy of functionalized SeNPs for
      therapy of colorectal cancer and reveals the important role of autophagy in
      promoting apoptosis and cell cycle arrest to induce cell death.

PMID- 30091750
TI  - Multifibrillar bundles of a self-assembling hyaluronic acid derivative obtained
      through a microfluidic technique for aortic smooth muscle cell orientation and
      differentiation.
AB  - A hyaluronic acid derivative that is able to physically crosslink in a saline
      aqueous environment was employed for the production of fibers with a mean
      diameter of 50 MUm using a microfluidic technique. The microfibers were collected
      in a tailored rotating collector and assembled to form multifibrillar bundles.
      The orientation of the microfibers on the collected bundles was evaluated by
      microCT analysis. The bundles were biofunctionalized by physical addition of
      fibronectin or chemical tethering of a cyRGDC peptide to achieve control of
      Aortic Smooth Muscle Cell (AoSMC) attachment, elongation and alignment. The
      mechanical performances of these bundles were evaluated by elongation tests,
      related to the kind of biological functionalization and compared to non
      functionalized samples. The alignment and differentiation of AoSMCs on single
      fibers and on the bundles were evaluated by microscopy and histochemical
      analyses.

PMID- 30091753
TI  - Access towards enantiopure alpha,alpha-difluoromethyl alcohols by means of
      sulfoxides as traceless chiral auxiliaries.
AB  - A new methodology to access enantiopure alpha,alpha-difluoromethyl alcohols is
      hereby being described. The strategy relies on the use of an enantiopure aryl
      alpha,alpha-difluoromethyl sulfoxide employed as chiral and removable auxiliary
      for the stereoselective difluoromethylation of carbonyl derivatives. The obtained
      alpha,alpha-difluoro-beta-hydroxysulfoxides displayed unprecedented
      diastereomeric ratios.

PMID- 30091755
TI  - Concise syntheses of eburnane indole alkaloids.
AB  - The asymmetric divergent syntheses of a group of C20 ethyl oxo-functionalized
      eburnane alkaloids, (-)-eburnaminol (5), (+)-larutenine (6), (-)-terengganensine
      B (7), (-)-strempeliopine (8), and (-)-terengganensine A (9), have been achieved.
      The key step in the assembly of the complex ring system of the target molecules
      is a photoredox catalytic nitrogen-centered radical cascade reaction, which
      allows the regioselective and stereoselective construction of the B, C, and D
      rings and the installation of the C21 chirality of the eburnane alkaloid skeleton
      in one pot.

PMID- 30091757
TI  - A general two-step one-pot synthesis process of ynones from alpha-keto acids and
      1-iodoalkynes.
AB  - A general two-step one-pot synthesis process of ynones was developed by
      cycloaddition of alpha-keto acids and 1-iodoalkynes followed by a ring-opening
      reaction. Its easy conditions and novel mechanism endowed it with two distinctive
      advantages: iodine-atom bonded to C(sp2) remained intact and alpha-keto acids
      became a part of the triple bonds in ynones.

PMID- 30091758
TI  - Rhodium(ii)-catalysed generation of cycloprop-1-en-1-yl ketones and their
      rearrangement to 5-aryl-2-siloxyfurans.
AB  - Donor-acceptor cyclopropenes formed from enoldiazoketones undergo catalytic
      rearrangement to 5-aryl-2-siloxyfurans via a novel mechanism that involves a
      nucleophilic addition of the carbonyl oxygen to the rhodium-activated
      cyclopropene.

PMID- 30091760
TI  - Lanthanide-doped core-shell nanoparticles as a multimodality platform for imaging
      and photodynamic therapy.
AB  - We report a novel lanthanide-doped core-shell nanostructure
      NaYF4:Yb,Er@NaGdF4:Nd@SiO2-RB with a unique design feature that integrates
      luminescence imaging in biological window II, magnetic resonance imaging, and NIR
      excited photodynamic antimicrobial chemotherapy, in a single nanoscale entity.

PMID- 30091759
TI  - Real-time tracking of single-molecule collagenase on native collagen and
      partially structured collagen-mimic substrates.
AB  - The dynamic interactions of an individual matrix metalloproteinase-1 were imaged
      and monitored in the presence of either triple-helical or non-triple-helical,
      partially structured collagen-mimic substrates. The enzyme exhibited ten-fold
      increased catalytic turnover rates with the structurally modified substrate by
      skipping the triple-helix unwinding step during the catalytic pathway.

PMID- 30091761
TI  - Energy dissipation to tungsten surfaces upon hot-atom and Eley-Rideal
      recombination of H2.
AB  - Adiabatic and nonadiabatic quasi-classical molecular dynamics simulations are
      performed to investigate the role of electron-hole pair excitations in hot-atom
      and Eley-Rideal H2 recombination mechanisms on H-covered W(100). The influence of
      the surface structure is analyzed by comparing with previous results for W(110).
      In the two surfaces, hot-atom abstraction cross sections are drastically reduced
      due to the efficient energy exchange with electronic excitations at low incident
      energies and low coverage, while the effect on Eley-Rideal reactivity is
      negligible. As the coverage increases, the projectile energy is more efficiently
      dissipated into the other adsorbates. Consequently, the effect of electronic
      excitations is reduced. As a result, the reactivity and final energy
      distributions of the formed H2 molecules are similar for both abstraction
      mechanisms.

PMID- 30091762
TI  - A physiochemical processing kinetics model for the vapor phase infiltration of
      polymers: measuring the energetics of precursor-polymer sorption, diffusion, and
      reaction.
AB  - Vapor phase infiltration (VPI) is a new approach for transforming polymers into
      organic-inorganic hybrid materials with unique properties. Here, we combine
      experimental measurements with phenomenological theory to develop a universal
      strategy for measuring, modeling, and predicting the processing kinetics of VPI.
      We apply our approach to the well-studied VPI system of trimethylaluminum (TMA)
      infiltrating poly(methyl methacrylate) (PMMA) because the system undergoes both
      precursor-polymer diffusion and reaction. By experimentally measuring aluminum
      concentration profiles as a function of film depth with secondary ion mass
      spectrometry (SIMS) and film swelling with ellipsometry, we have extracted
      equilibrium solubility and effective diffusivity as a function of process
      temperature. Fitting these values to appropriate Van't Hoff and Arrhenius
      relationships, we can then extract enthalpies for precursor sorption and
      diffusion. We observe an abrupt mechanistic change in both the sorption and
      diffusion processes around 95  degrees C, where greater chain mobility at higher
      processing temperatures lead to greater reactivity between TMA and PMMA. With new
      understanding of this VPI process, we demonstrate precise control of inorganic
      infiltration depth and loading fraction into PMMA.

PMID- 30091763
TI  - In situ gold nanoparticle growth on polydopamine-coated 3D-printed scaffolds
      improves osteogenic differentiation for bone tissue engineering applications: in
      vitro and in vivo studies.
AB  - In this study, we designed scaffolds coated with gold nanoparticles (GNPs) grown
      on a polydopamine (PDA) coating of a three-dimensional (3D) printed
      polycaprolactone (PCL) scaffold. Our results demonstrated that the scaffolds
      developed here may represent an innovative paradigm in bone tissue engineering by
      inducing osteogenesis as a means of remodeling and healing bone defects.

PMID- 30091764
TI  - In situ study of the precursor conversion reactions during solventless synthesis
      of Co9S8, Ni3S2, Co and Ni nanowires.
AB  - Synthesis of Co9S8, Ni3S2, Co and Ni nanowires by solventless thermolysis of a
      mixture of metal(ii) acetate and cysteine in vacuum is reported. The simple
      precursor system enables the nanowire phase to be tuned from pure metal (Co or
      Ni) to metal sulfide (Co9S8, Ni3S2) by varying the relative concentration of the
      metal(ii) acetate. The growth environment facilitates new insights through in
      situ characterization using field-emission scanning electron microscopy (FESEM)
      and thermogravimetric analysis with gas chromatography-mass spectrometry (TGA-GC
      MS). Direct observation by FESEM shows the temperature at which nanowire growth
      occurs and suggests adatoms are incorporated into the base of the growing
      nanowire. TGA-GC-MS reveals the rates of precursor decomposition and identity of
      the volatilized ligand fragments during heat-up and at the nanowire growth
      temperature. Our results constitute a new approach for the selective fabrication
      of high quality Co9S8 and Ni3S2 nanowires and more importantly provides new
      understanding of precursor decomposition reactions that support symmetry-breaking
      growth in nanocrystals by heat-up synthesis.

PMID- 30091765
TI  - Giant enhancement and facile tuning of photoluminescence in a soft anisotropic
      magneto-gel.
AB  - A soft photoluminescent composite, prepared using a nematic liquid crystal and a
      fluorescent gelator, exhibits a nearly two orders of magnitude increase in
      fluorescence on addition of superparamagnetic nanoparticles. The internal
      magnetic field generated leading to an increase in the population of singlet
      excitons which affects the radiative efficiency, and enhanced ordering of the LC
      environment are proposed to be responsible for the large increase seen in
      fluorescence. Also, the nematic nature of the host liquid crystal medium aids in
      switching of the fluorescence intensity between its anisotropic limits on
      application of an external electric field with the switch-off time being faster
      compared to the field-driven switch-on time.

PMID- 30091766
TI  - A spent hen muscle protein hydrolysate: a potential IL-10 stimulator in a murine
      model.
AB  - Dietary proteins harbour bioactive peptides that exert various physiological
      activities. Chicken meat prepared from spent layers from the egg industry is an
      inexpensive source of protein for the production of bioactive peptides. This
      study explored the effect of hen muscle-derived peptides prepared by enzymatic
      hydrolysis on immune functions. The hydrolysate was incorporated into the diet of
      weanling Sprague-Dawley rats (n = 8 per diet) for 3 weeks at 2% or 5% addition
      (w/w diet). At a dose of 5% (w/w) the hydrolysate exhibited immunomodulatory
      effects on splenocytes, including a lower proportion of OX6+ (professional
      antigen presenting cells) and a higher proportion of CD11b/c+ cells
      (macrophages/monocytes) (p < 0.05) compared to the isonitrogenous control diet.
      Meanwhile, the production of anti-inflammatory cytokine interleukin (IL)-10 by
      splenocytes stimulated ex vivo with mitogens was significantly higher from
      hydrolysate treatment; there was no significant difference in the other cytokines
      (IL-1beta, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, IL-6 and IL
      2) investigated. Supplementing with the hydrolysate did not alter the growth,
      food intake and organ weights in young rodents. These results indicated that the
      spent hen muscle protein hydrolysate has the potential to be developed for value
      added products with anti-inflammatory properties.

PMID- 30091768
TI  - Cu dimer anchored on C2N monolayer: low-cost and efficient Bi-atom catalyst for
      CO oxidation.
AB  - By means of density functional theory (DFT) computations, we systemically
      investigated CO/O2 adsorption and CO oxidation pathways on a bi-atom catalyst,
      namely, a copper dimer anchored on a C2N monolayer (Cu2@C2N), and we compared it
      with its monometallic counterpart Cu1@C2N. The Cu dimer could be stably embedded
      into the porous C2N monolayer. The reactions between the adsorbed O2 and CO via
      both bi-molecular and tri-molecular Langmuir-Hinshelwood (L-H) and Eley-Rideal (E
      R) mechanisms were comparably studied, and we found that the bi-atom catalyst
      Cu2@C2N possessed superior performance toward CO oxidation as compared to the
      single-atom catalyst Cu1@C2N. Our comparative study suggested that the newly
      predicted bi-atom catalyst, i.e., a copper dimer anchored on a suitable support
      is highly active for CO oxidation, which can provide a useful guideline for
      further developing highly effective and low-cost green nanocatalysts.

PMID- 30091769
TI  - Mitochondria-targeting nanoparticles for enhanced microwave ablation of cancer.
AB  - Although microwave ablation is widely used in the treatment of hepatocellular
      carcinoma, it is only recommended for the therapy of cancer with a diameter of 3
      cm or less because of the limited heat transmission radius. Mitochondria play an
      important role in the apoptotic events of tumor cells. Here, we developed
      mitochondria-targeting zirconia (ZrO2) complex nanoparticles (MZCNs) as
      nanoagents for efficient cancer therapy by microwave ablation. The MZCNs are
      composed of ZrO2 nanoparticles encapsulating the microwave-sensitive ionic liquid
      (IL) and co-decorated with the mitochondria-targeting molecule of
      triphenylphosphonium (TPP), and the tumor cell-targeting peptide iRGD. The cell
      experiment results reveal that the amount of MZCNs accumulated in the tumor is
      obviously increased by the synergistically targeted delivery of TPP and iRGD
      peptide after administration by intravenous injection. Besides, the in vitro
      experiments demonstrate that MZCNs are distributed preferentially in the
      mitochondria with the assistance of TPP molecules. More importantly, the in vivo
      experiments in mice administered with MZCNs show that the effective area with a
      temperature above 42  degrees C was about 2.8-fold larger than that of the
      controls due to the targeting effect and better microwave sensitivity of the
      MZCNs. As such, the cancer in mice can be eradicated without recurrence,
      demonstrating the MZCNs as promising nanoagents for efficient cancer therapy by
      microwave ablation.

PMID- 30091770
TI  - Investigating supramolecular systems using Forster resonance energy transfer.
AB  - Supramolecular systems have applications in areas as diverse as materials
      science, biochemistry, analytical chemistry, and nanomedicine. However, analyzing
      such systems can be challenging due to the wide range of time scales, binding
      strengths, distances, and concentrations at which non-covalent phenomena take
      place. Due to their versatility and sensitivity, Forster resonance energy
      transfer (FRET)-based techniques are excellently suited to meet such challenges.
      Here, we detail the ways in which FRET has been used to study non-covalent
      interactions in both synthetic and biological supramolecular systems. Among other
      topics, we examine methods to measure molecular forces, determine protein
      conformations, monitor assembly kinetics, and visualize in vivo drug release from
      nanoparticles. Furthermore, we highlight multiplex FRET techniques, discuss the
      field's limitations, and provide a perspective on new developments.

PMID- 30091771
TI  - High-throughput single-molecule bioassay using micro-reactor arrays with a
      concentration gradient of target molecules.
AB  - Micro-reactor arrays enable highly sensitive and quantitative bioassays at a
      single-molecule level. Accordingly, they are widely used for sensitive "digital"
      bioassays, e.g., digital PCR and digital ELISA. Despite high integration,
      individual reactors in digital bioassays are filled with a uniform reaction
      solution, thus limiting the ability to simultaneously conduct multiple bioassays
      under different conditions using integrated reactors in parallel, resulting in
      the loss of potential throughput. We developed micro-reactor arrays with a
      concentration gradient of target molecules, in which individual reactors sealed
      with a lipid-bilayer membrane contained a precise amount of target molecules.
      Using the arrays, we successfully demonstrated multiple single-molecule bioassays
      in parallel using alkaline phosphatase or alpha-hemolysin, key components in
      various biomedical sensors. This new platform extends the versatility of micro
      reactor arrays and could enable further analytical and pharmacological
      applications.

PMID- 30091773
TI  - Visible light induced electron transfer from a semiconductor to an insulator
      enables efficient photocatalytic activity on insulator-based heterojunctions.
AB  - Photogenerated electrons play a vital role in photocatalysis as they can induce
      the formation of radicals participating in the reaction or recombine with holes
      preventing them from the subsequent redox reaction. In this work, we explore an
      Earth-abundant insulator coupled with a semiconductor and construct insulator
      semiconductor heterojunctions to effectively realize the efficient electron
      transfer from the semiconductor to the insulator and thus the enhanced charge
      carrier separation on the semiconductor. This result will challenge the
      traditional opinion that free electrons cannot be transferred onto insulators.
      Taking the BaCO3 insulator as a case study, the combined experimental and
      theoretical evidence indicates that the photogenerated electrons from the BiOI
      semiconductor could transfer directly to the BaCO3 insulator through a preformed
      electron delivery channel when they are coupled to form BaCO3/BiOI
      heterojunctions. The potential difference between the Bi layer of BiOI (5.03 eV)
      and the carbonate layer of BaCO3 (12.37 eV) would drive the transfer of excited
      electrons from Bi atoms across the energy barrier to the adjacent carbonate layer
      under visible light irradiation. Consequently, the free electrons on BaCO3 can be
      utilized to produce the oxidative radicals (OH, O2- and 1O2) participating in the
      photocatalytic oxidation reaction. The in situ FT-IR spectra illustrate that the
      visible light induced active species in the heterojunctions could react with NO,
      leading to its oxidation to high valence state intermediates (NO+ and NO2+) first
      and then conversion to the final product of nitrates. This research offers new
      perspectives to explore insulator-based photocatalysts and unravel the gas-phase
      photocatalytic reaction mechanism.

PMID- 30091772
TI  - Towards superlubricity in nanostructured surfaces: the role of van der Waals
      forces.
AB  - Hydrogenated amorphous carbon (a-C:H) thin films have a unique combination of
      properties that are fundamental in mechanical and electromechanical devices aimed
      at energy efficiency issues. The literature brings a wealth of information about
      the ultra-low friction (superlubricity) mechanism in a-C:H thin films. However,
      there is persistent controversy concerning the physicochemical mechanisms of
      contact mechanics at the atomic/molecular level and the role of electrical
      interactions at the sliding interface is still a matter of debate. We find that
      the hydrogenation of the outermost nanostructured surface atomic layers of a-C:H
      thin films is proportional to the surface potential and also to the friction
      forces arising at the sliding interface. A higher hydrogen-to-carbon ratio
      reduces the surface potential, directly affecting frictional forces by a less
      effective long-term interaction. The structural ultra-low friction
      (superlubricity) is attributed to a lower polarizability at the outermost
      nanostructured layer of a-C:H thin films due to a higher hydrogen density, which
      renders weaker van der Waals forces, in particular London dispersion forces. More
      hydrogenated nanodomains at the surface of a-C:H thin films are proposed to be
      used to tailor superlubricity.

PMID- 30091774
TI  - Highly crumpled nanocarbons as efficient metal-free electrocatalysts for zinc-air
      batteries.
AB  - The rational design of an efficient and robust oxygen reduction reaction (ORR)
      electrocatalyst is vital for energy conversion and storage systems, especially
      for metal-air batteries. Herein, we report a highly nanocrumpled and nitrogen,
      phosphorus-codoped nanocarbon (NC-NPC) synthesized by direct pyrolysis of
      melamine and triphenylphosphine. With the rich nano-crumpled structure and
      codoping of heteroatoms, this low-cost catalyst exhibits an excellent ORR
      performance, and possesses a half-wave potential of 0.84 V vs. RHE, a small Tafel
      slope of 70.2 mV dec-1, and good electrocatalytic stability. More importantly, it
      can also be applied in zinc-air batteries as an efficient electrode which
      delivers an open-circle voltage of 1.38 V, a specific capacity of 782 mA h gZn-1,
      and a long cycling life of 210 h, superior to the commercial Pt/C catalyst.

PMID- 30091775
TI  - Self-assembly of semiflexible polymers confined to thin spherical shells.
AB  - Confinement effects are critical for stiff macromolecules in biological cells,
      vesicles, and other systems in soft matter. For these molecules, the competition
      between the packing entropy and the enthalpic cost of bending is further shaped
      by strong confinement effects. Through coarse-grained molecular dynamics
      simulations, we explore the self-assembly of semiflexible polymers confined in
      thin spherical shells for various chain lengths, chain stiffnesses, and shell
      thicknesses. Here, we focus on the case where the contour and persistence length
      of the polymers are comparable to the radius of the confining cavity. The range
      of ordered structures is analyzed using several order parameters to elucidate the
      nature of orientational ordering in different parameter regimes. Previous
      simulations have revealed the emergence of bipolar and quadrupolar topological
      defects on the surface when the entire cavity was filled with a concentrated
      polymer solution [Phys. Rev. Lett., 2017, 118, 217803]. In contrast, spherical
      shell confinement restricts the appearance of a bipolar order. Instead, only the
      extent of the quadrupolar order changes with chain stiffness, as evidenced by the
      relative motion of topological defects. In the case of monolayers, we observe a
      nematic to smectic transition accompanied by a change in the nematic grain-size
      distribution as the contour length was decreased.

PMID- 30091776
TI  - Atomic-engineered gold@silvergold alloy nanoflowers for in vivo inhibition of
      bacteria.
AB  - The problems of multidrug-resistant bacteria and environmental pollution
      associated with the abuse of antibiotics call for effective antibiotic
      alternatives. Here, gold@silvergold alloy nanoflowers (Au@AgAu ANFs) with
      distinct atomic structures are first fabricated and then demonstrated for in vivo
      inhibition of bacteria. The Au@AgAu ANFs display high antibacterial activity
      against the model Gram-negative bacterium Escherichia coli, with a minimum
      inhibitory concentration value of 4.8 MUg mL-1, which is 3.1 times lower than
      that of silver nanoparticles. The alloy structure with a rough surface enables
      Au@AgAu ANFs to firmly adhere to the bacterial surface and damage the cell
      membrane, resulting in long-term (48 h) and highly stable (30 days) antibacterial
      activity. Meanwhile, the Au@AgAu ANFs show remarkable biocompatibility with human
      cells even at a high concentration of 40 MUg mL-1. Application of Au@AgAu ANFs in
      the treatment of bacterial infections in the mouse intestine significantly
      reduces the reproduction of bacteria compared to an untreated mouse, giving
      results similar to those of the current antibiotic treatment, with no
      cytotoxicity. Our study opens up a new avenue for the rational design of safe and
      highly efficient antibacterial materials.

PMID- 30091777
TI  - Complex liquid crystal superstructures induced by periodic photo-alignment at top
      and bottom substrates.
AB  - The formation of nematic liquid crystal (LC) superstructures in cells with non
      uniform photo-alignment at the confining substrates is studied experimentally and
      by simulations. An interference pattern of left- and right-handed circularly
      polarized light is used to define the alignment at both substrates separately, so
      that the alignment varies along the x-coordinate on one substrate and along the y
      coordinate on the other substrate. The interplay between the complex surface
      alignment and the liquid crystalline soft matter leads to the formation of
      interesting 3D configurations. The periodic LC structures that are formed in the
      bulk of the cell are analyzed experimentally by polarizing optical microscopy
      (POM) for different applied voltages. In the region with strong photo-alignment
      at both substrates, a 2D LC polarization grating (PG) with a complex 3D director
      configuration is formed. Distinct periodic structures with different symmetry
      properties are observed in the regions with weak illumination at the top and/or
      bottom substrate. The director configuration in the different regions was
      successfully simulated with the help of finite element (FE) Q-tensor simulations.
      The agreement between the simulations and the experiments was verified by
      comparing the POM images with simulated results for the transmission between
      crossed polarizers.

PMID- 30091778
TI  - Synthesis of 2,2-difluoro-homoallylic alcohols via ring-opening of gem
      difluorocyclopropane and aerobic oxidation by photo-irradiation in the presence
      of an organic pigment.
AB  - We found that aerobic oxidation took place after the visible light-mediated ring
      opening reaction of gem-difluorocyclopropane in the presence of an organic dye
      and amine to furnish 2,2-difluoro-homoallylic alcohols in good yields.

PMID- 30091779
TI  - Copper-catalyzed oxidative multicomponent reaction: synthesis of imidazo fused
      heterocycles with molecular oxygen.
AB  - An oxidative cascade that involves multicomponent reaction comprising a terminal
      alkyne, 2-amino N-heterocycle, benzyl or allylic bromide with molecular oxygen,
      delivering densely functionalized imidazo fused heterocycles, is described. This
      reaction features a cheap catalyst, a green oxidant, and readily available
      starting materials, which make the overall synthesis applicable in the quick
      access to relevant pharmaceutical molecules with imidazole derived heterocycles.

PMID- 30091781
TI  - Conjugation of a GM3 lactone mimetic on carbon nanotubes enhances the related
      inhibition of melanoma-associated metastatic events.
AB  - GM3-ganglioside is known to be involved in melanoma proliferation. In order to
      modulate metastatic-related events, we have functionalized multi-walled carbon
      nanotubes (MWCNTs) with multiple copies of a GM3-lactone mimetic. The MWCNTs
      proved to guarantee the appropriate spatial arrangement of the mimetic allowing a
      stronger inhibition of migration and invasiveness of human melanoma (A375) cells
      compared to other multivalent constructs reported before. In addition, the effect
      of the multivalent tubular conjugate on the inhibition of specific tyrosine
      kinases, which are associated with the ganglioside complexes within the membrane
      domains, was demonstrated. Finally, the short-term fate of the conjugate was
      assessed, for the first time, by means of the 1H NMR relaxometry technique by
      exploiting the signal arising from the CNTs.

PMID- 30091780
TI  - Extended photo-induced endosome-like structures in giant vesicles promoted by
      block-copolymer nanocarriers.
AB  - Upon irradiation, the photosensitizer pheophorbide-a causes dramatic
      morphological transitions in giant unilamellar lipid vesicles. This endocytosis
      like process occurs only when the photoactive species are encapsulated in a
      copolymer nanocarrier and strictly depends on the chemical nature of the
      copolymer. Altogether, these results open up new perspectives in the field of
      photo-chemical internalization mediated by nanoassemblies.

PMID- 30091782
TI  - One-pot synthesis of beta-lactams by the Ugi and Michael addition cascade
      reaction.
AB  - Diversity-oriented synthesis of beta-lactams was achieved via Ugi/Michael
      reaction cascades under mild conditions. The intramolecular hydrogen bonding
      between the heteroatom from an aldehyde component and the amide NH group controls
      the chemoselectivity of the Michael reaction versus the aza-Michael reaction. DFT
      calculation was performed to clarify the mechanism, chemo-selectivity and
      diastereoselectivity of this work. This one-pot protocol offers a straightforward
      method to build a diversified beta-lactam library for drug discovery.

PMID- 30091783
TI  - Long-range stress correlations in viscoelastic and glass-forming fluids.
AB  - A simple and rigorous approach to obtain stress correlations in viscoelastic
      liquids (including supercooled liquid and equilibrium amorphous systems) is
      proposed. The long-range dynamical correlations of local shear stress are
      calculated and analyzed in 2-dimensional space. It is established how the long
      range character of the stress correlations gradually emerges as the relevant
      dynamical correlation length l grows in time. The correlation range l is defined
      by momentum propagation due to acoustic waves and vorticity diffusion which are
      the basic mechanisms for transmission of shear stress perturbations. We obtain
      the general expression defining the time- and distance-dependent stress
      correlation tensor in terms of material functions (generalized relaxation
      moduli). The effect of liquid compressibility is quantitatively analyzed; it is
      shown to be important at large distances and/or short times. The revealed long
      range stress correlation effect is shown to be dynamical in nature and
      unconnected with static structural correlations in liquids (correlation length
      xis). Our approach is based on the assumption that xis is small enough as
      reflected in weak wave-number dependencies of the generalized relaxation moduli.
      We provide a simple physical picture connecting the elucidated long-range
      fluctuation effect with anisotropic correlations of the (transient) inherent
      stress field, and discuss its implications.

PMID- 30091784
TI  - Assessing the evolutionary history of the fern family Dipteridaceae
      (Gleicheniales) by incorporating both extant and extinct members in a combined
      phylogenetic study.
AB  - PREMISE OF THE STUDY: Dipteridaceae is a lineage of ferns that has existed from
      the early Mesozoic and is known for its extensive fossil record. By integrating
      information from all described extant and extinct genera into a single
      phylogenetic study, this paper aims to examine the taxonomy of the group on a
      whole and explore character evolution within the lineage across time. METHODS: A
      morphological matrix of 51 characters was developed for 72 species (43 extinct
      and 29 extant) based on published information. Morphological characters were
      combined with nucleotide sequences for four chloroplast genes (rbcL, atpA, atpB,
      and rps4) for extant taxa, and combined parsimony analyses were conducted to
      infer evolutionary trends in the group. KEY RESULTS: Dipteridaceae was found to
      be monophyletic and characterized by highly anastomosing minor veins forming a
      meshwork of areoles with free-included veinlets. Based on our analyses, we
      recognize six previously described genera (i.e., Goeppertella, Thaumatopteris,
      Clathropteris, Digitopteris, Dipteris, and Cheiropleuria) and one new genus
      (i.e., Sewardalea). Fossils currently described as Dictyophyllum, Kenderlykia,
      Hausmannia, and Protorhipis are ambiguously placed on the tree and are recognized
      as possibly unnatural morphogenera. CONCLUSIONS: Overall, the evolutionary trend
      in Dipteridaceae has been toward increasing complexity in the venation pattern
      and laminal fusion. Only the Hausmannia-type frond with dichotomizing primary
      veins and relatively fused lamina persisted in the later part of the Mesozoic to
      the present. Within the crown group, we see evidence of re-radiation of frond
      forms in Dipteris and Cheiropleuria.

PMID- 30091785
TI  - Incorporating fossils into the Pinaceae tree of life.
AB  - PREMISE OF THE STUDY: Pinaceae have a rich but enigmatic early fossil record,
      much of which is represented by permineralized seed cones. Our incomplete
      knowledge of morphology and anatomy in living and extinct species poses an
      important barrier to understanding their phylogenetic relationships and timing of
      diversification. METHODS: We expanded a morphology matrix to 46 fossil and 31
      extant Pinaceae species, mainly adding characters from stem and leaf anatomy and
      seed cones. Using parsimony and Bayesian inference, we compared phylogenetic
      relationships for extant taxa with and without fossils from the morphology matrix
      combined with an alignment of plastid gene sequences. KEY RESULTS: Combined
      analysis of morphological and molecular characters resulted in a phylogeny of
      extant Pinaceae that was robust at all nodes except those relating to the
      interrelationships of Pinus, Picea, and Cathaya and the position of Cedrus.
      Simultaneous analysis of all fossil and extant species did not result in changes
      in the relationships among the extant species but did greatly reduce branch
      support. We found that the placement of most fossils was sensitive to the method
      of phylogenetic reconstruction when analyzing them singly with the extant
      species. CONCLUSIONS: A robust phylogenetic hypothesis for the main lineages of
      Pinaceae is emerging. Most Early Cretaceous fossils are stem or crown lineages of
      Pinus, but close relationships also were found between fossils and several other
      extant genera. The phylogenetic position of fossils broadly supports the
      existence of extant genera in the Lower Cretaceous.

PMID- 30091786
TI  - Moral judgment, political ideology and collective action.
AB  - This study aimed to further the understanding of the processes involved in
      activism, as a form of collective action, based on differences in the quality of
      moral judgment and political ideology. It began with the assumption that
      differences in the quality of moral judgment can lead individuals to engage in
      different forms of collective action: activism or radicalism. Therefore, the
      associations among the variables political ideology, social identity, perception
      of social justice, activist identity and commitment, personal political salience,
      perception of efficacy and life purpose were analyzed. Path modelling was used to
      construct two models of political action: one based on conventional moral
      judgment and conservative political ideology, and the other based on post
      conventional moral judgment and egalitarian political ideology. These two models
      were tested on samples of Brazilian and Spanish youths. The results confirmed the
      validity of using developmental social psychology to understand activism as a
      form of political action. The results confirmed the central hypothesis that
      differences in the quality of moral judgment and in political ideology are
      related to willingness to engage in qualitatively different types of actions:
      young people with conventional moral judgment and conservative political ideology
      declared their intention to engage in activism, while young people with post
      conventional moral judgment egalitarian political ideology reported the intention
      to engage in both activist and radical actions.

PMID- 30091788
TI  - Subdural Hygroma: A Case Report of an Uncommon Persistence of Elevated
      Intracranial Pressure.

PMID- 30091787
TI  - Shedding new light on the origin and spread of the brinjal eggplant (Solanum
      melongena L.) and its wild relatives.
AB  - PREMISE OF THE STUDY: While brinjal eggplant (Solanum melongena L.) is the second
      most important solanaceous fruit crop, we lack firm knowledge of its evolutionary
      relationships. This in turn limits efficient use of crop wild relatives in
      eggplant improvement. Here, we examine the hypothesis of linear step-wise
      expansion of the eggplant group from Africa to Asia. METHODS: We use museum
      collections to generate nuclear and full-plastome data for all species of the
      Eggplant clade. We combine a phylogenomic approach with distribution data to
      infer a biogeographic scenario for the clade. KEY RESULTS: The Eggplant clade has
      Pleistocene origins in northern Africa. Dispersals to tropical Asia gave rise to
      Solanum insanum, the wild progenitor of the eggplant, and to African distinct
      lineages of widespread and southern African species. Results suggest that spread
      of the species to southern Africa has been recent and likely facilitated by large
      mammalian herbivores, such as the African elephant and impala feeding on Solanum
      fruit. CONCLUSIONS: Rather than a linear 'Out Of Africa' sequence, our results
      are more consistent with an initial dispersal event into Asia, and subsequent
      wide dispersal and differentiation across Africa driven by large mammalian
      herbivores. Our evolutionary results will affect future work on eggplant
      domestication and affect the use of wild relatives in breeding of this
      increasingly important solanaceous crop.

PMID- 30091789
TI  - Quantitative detection of hepatitis C virus RNA in urine of patients with chronic
      hepatitis C using a novel real-time PCR assay.
AB  - Hepatitis C virus (HCV) RNA can be detected in body fluids such as urine.
      However, because of deficiencies in established isolation and detection methods,
      the actual prevalence and form of HCV RNA in the urine of patients with hepatitis
      C remain unclear. To more sensitively and accurately measure urine HCV RNA
      levels, a novel real-time PCR assay with a modified isolation method and short
      amplicon designed for short HCV RNA fragments was developed in this study. The
      limit of detection, precision, linearity, and specificity of the assay was
      evaluated and demonstrated high-quality performance. The prevalence of HCV RNA in
      the urine of viremic patients infected with HCV was 60% (36/60), as determined by
      a 62-bp assay. The HCV RNA detection rate and concentration were much lower with
      a 157-bp assay, and were undetectable with 222- and 304-bp assays. With the 62-bp
      assay, patients with detectable urine HCV RNA had significantly higher plasma HCV
      RNA levels ( P < 0.001), and plasma and urine concentrations were significantly
      positively correlated ( R 2  = 0.708, P < 0.001). The method not only increased
      the detection rate of urine HCV RNA but also revealed the presence of short HCV
      RNA fragments in urine, indicating that urine from CHC patients with normal
      kidney function should not be infectious. In addition, it raised the possibility
      of urinary HCV RNA as a potential noninvasive marker for therapeutic monitoring
      of patients with hepatitis C.

PMID- 30091791
TI  - Cromolyn/gelatin mixtures as aqueous alignment media and utilization of their
      mechanical stability for a layering technique.
AB  - In this study, aqueous blends of cromolyn and gelatin ("cromogels") are
      introduced as anisotropic media. The addition of gelatin enables an advantageous
      adjustability of the strength, the homogeneity, and the stability of the cromolyn
      alignment. The mechanical stability of these polymer-dispersed liquid crystals is
      further utilized by stacking layers of D2 O/cromolyn/gelatin with varying
      component ratio. The resulting distinct phases with correspondingly different
      degrees of alignment can be targeted by spatially resolved NMR techniques. As a
      case study, we investigated sucrose in a two-phase system with neat D2 O and
      analyte layered over the anisotropic medium. A recently presented spatially
      selective coupled-type HSQC experiment allows the determination of one-bond C-H
      splitting in both phases.

PMID- 30091792
TI  - Playing it close to the VEST and the clinical guidelines: Clinical guideline
      compliance in HFrEF patients-Role of WCD.
AB  - BACKGROUND: Guideline-directed medical therapy (GDMT) for patients with heart
      failure with reduced ejection fraction (HFrEF) has been challenging to achieve
      universally. Healthcare providers who seek to achieve optimal medical therapy
      frequently consider either a wearable cardioverter defibrillator (WCD) or an
      implantable cardioverter defibrillator (ICD) as indicated. The dynamic process of
      communication and physician recommendations marks a setting to study the relative
      interdependence of medical therapies and best practice. The purpose of this study
      was to examine the long-term impact of the WCD on GDMT. We hypothesized the WCD
      serves as a "gateway" therapy, likely impacting other optimal strategies such
      that successful use of WCD improves GDMT adherence. METHODS: Electronic medical
      records (EPIC) were manually reviewed to extract data elements in this
      observational study of 1289 HFrEF patients from 2013-2015. Data included
      demographics, comorbidities, and use of GDMT including an ICD use in persistently
      low ejection fraction (<=36%) patients after 90 days. RESULTS: WCD use was
      significantly associated with prescribing adherence to GDMT, chi2 (1, N = 981) =
      33.36, P < 0.001. Further, WCD use was significantly associated with
      recommendations for follow-up echocardiographic study, chi2 (1, N = 865) = 66.94,
      P < 0.001 and use of primary prevention ICD, chi2 (1, N = 1093) = 19.00, P <
      0.001. CONCLUSIONS: This study demonstrates the use of the WCD correlates with
      improved clinician use of GDMT, follow-up echocardiographic studies, and
      appropriate use of primary prevention ICD. Thus, the potential benefits of the
      WCD and its care processes may extend beyond prevention of sudden cardiac death
      to enhanced optimization of GDMT.

PMID- 30091793
TI  - Detection of HCV genome in peripheral blood mononuclear cells of Iranian
      seropositive and HCV RNA negative in plasma of patients with beta-thalassemia
      major: Occult HCV infection.
AB  - Beta (beta) thalassemia major is a genetic blood disorder with a deficiency in
      the hemoglobin beta chain, requiring blood transfusion therapy. Multiple blood
      transfusions increase the risk of transmitting blood-borne infections. The aim of
      this study is to determine the frequency of hepatitis C virus (HCV) infection in
      Iranian individuals with beta-thalassemia major. A total of 164 patients with
      beta-thalassemia major were recruited for this study. HCV RNA testing was done on
      plasma and peripheral blood mononuclear cells (PBMCs) from the HCV seropositive
      samples (with reverse transcriptase-nested polymerase chain reaction [PCR] method
      using primers from the 5'-untranslated region [UTR]), and all HCV RNA positive
      samples were genotyped by the restriction fragment length polymorphism assay. For
      confirmation of the HCV genotyping in PBMCs of occult HCV infection [OCI]
      positive patients, the PCR products of two different regions of HCV (5'-UTR and
      nonstructural protein 5B [NS5B]) were sequenced. Of 164 patients, 29.3% were
      positive for anti-HCV antibodies, and HCV RNA was detected in the plasma
      specimens of 13.4% patients and in the PBMC samples of 15.2% participants. The
      genomic HCV-RNA was detected in PBMC samples in 3 (6.3%) of the total 48
      individuals who were HCV seropositive, and plasma HCV-RNA negative (occult HCV
      infection). The subtypes of HCV in the plasma and PBMC samples of three
      participants were not identical. This study shows that among this group of
      Iranian patients with beta-thalassemia major, 13.4% had active HCV infection and
      6.3% had occult HCV infection as evidenced by HCV RNA detected in PBMC specimens.
      Therefore, the design of a prospective study that focuses on the diagnosis of OCI
      can be very valuable and provide more information.

PMID- 30091794
TI  - Tessellated fundus appearance and its association with myopic refractive error.
AB  - The appearance of tessellated fundus in an eye may act as a marker in identifying
      visual performance, degree of myopia or risk of progression of myopia in a given
      eye. A systematic literature search using key words was performed using PubMed,
      Web of Science and Google Scholar and of the 832 studies identified, 10 full
      length articles, which met the inclusion criteria, were considered for review.
      The primary outcome measures were association of tessellated fundus with: (i)
      visual acuity, (ii) refractive error, (iii) axial length, (iv) choroidal
      thickness and (v) future progression of myopia when compared to either no myopic
      maculopathy, or more severe myopic maculopathy. There was no significant
      difference in the visual acuity noted between eyes with normal fundus and
      tessellated fundus appearance. Compared to eyes with tessellated fundus, eyes
      with more severe myopic maculopathy had a four-line decrease in best-corrected
      visual acuity, more myopia (mean difference 2.75 D, range 0.28-5.78 D) and a
      longer axial length (mean difference 2 mm, range 2.29 to 1.71 mm). Eyes with
      tessellated fundus generally exhibited a significant decrease in choroidal
      thickness compared to eyes with no maculopathy. In mostly older individuals, eyes
      with tessellated fundus had a better outcome with respect to visual acuity,
      degree of myopia and axial length compared to other severe myopic maculopathies,
      but had a worse outcome for choroidal thickness and degree of myopia, compared to
      eyes with no myopic maculopathy. The features such as reduced choroidal thickness
      combined with a predilection to infra-temporal and parapapillary regions may
      indicate regions of stress that are prone to more stretching/atrophic changes.
      This systematic review demonstrated an association of tessellated fundus with
      visual acuity, refractive error, axial length and choroidal thickness and hence
      emphasises the documentation of the presence and location of tessellated fundus
      appearance that may help in predicting the progression of myopia.

PMID- 30091796
TI  - Characterization of the suppressive effects of extremely-low-frequency electric
      fields on a stress-induced increase in the plasma glucocorticoid level in mice.
AB  - We recently suggested that an increase in the plasma glucocorticoid (GC) level in
      immobilized mice is suppressed by a 50-Hz electric field (EF) in an EF strength
      dependent manner. The present study aimed to assess the anti-stress effect of EFs
      in three scenarios: exposure to an EF of either 50 or 60 Hz, which are the
      standard power frequencies in most regions; varying levels of environmental
      brightness during EF exposure; complete or partial shielding of the mouse from
      the EF. We compared the GC levels and blood parameters among control, EF-alone,
      immobilization-alone, and co-treatment groups. There was no difference between
      EFs of 50 and 60 Hz in terms of the suppression of the immobilization-induced
      increase in GC, that is, the anti-stress effect upon EF exposure. Examination of
      the effects of three environmental illuminance levels, 0, 200, and 490 lux,
      revealed that the effect of the EF was influenced by environmental illuminance.
      Shielding of the mice from the EF by wrapping the animals with an electrically
      conductive sheet inhibited the EF effect, which showed a negative correlation
      with the area shielded. Hence, environmental illuminance and the body area
      exposed to the EF might influence the effects of an EF on stress-induced
      increases in plasma GC levels in mice. Because stress plays an important role in
      the onset and progression of various diseases, these findings may have broad
      implications for understanding the efficacy of EFs in health.
      Bioelectromagnetics. 39:516-528, 2018 (c) 2018 Wiley Periodicals, Inc.

PMID- 30091795
TI  - Ataxia telangiectasia mutated deficiency does not result in genetic
      susceptibility to 50 Hz magnetic fields exposure in mouse embryonic fibroblasts.
AB  - Extremely low frequency magnetic field (ELF-MF) has been classified as a possible
      carcinogen to humans by the International Agency for Research on Cancer [2002].
      However, debate on the genotoxic effects of ELF-MF has continued due to lack of
      sufficient experimental evidence. Ataxia telangiectasia mutated (ATM) plays a
      central role in DNA damage repair; its deficiency can result in cellular
      sensitivity to DNA-damaging agents. To evaluate the genotoxicity of ELF-MF, we
      investigated the effects of 50 Hz MF on DNA damage in ATM-proficient (Atm+/+ )
      mouse embryonic fibroblasts (MEFs) and ATM-deficient (Atm-/- ) MEFs, a
      radiosensitive cell line. Results showed no significant difference in average
      number of gammaH2AX foci per cell (9.37 +/- 0.44 vs. 9.08 +/- 0.28, P = 0.58) or
      percentage of gammaH2AX foci positive cells (49.22 +/- 1.86% vs. 49.74 +/- 1.44%,
      P = 0.83) between sham and exposure groups when Atm+/+ MEFs were exposed to 50 Hz
      MF at 2.0 mT for 15 min. Extending exposure duration to 1 or 24 h did not
      significantly change gammaH2AX foci formation in Atm+/+ MEFs. Similarly, the
      exposure did not significantly affect gammaH2AX foci formation in Atm-/- MEFs.
      Furthermore, 50 Hz MF exposure also did not significantly influence DNA
      fragmentation, cell viability, or cell cycle progression in either cell types. In
      conclusion, exposure to 50 Hz MF did not induce significant DNA damage in either
      Atm+/+ or Atm-/- MEFs under the reported experimental conditions.
      Bioelectromagnetics. 39:476-484, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30091797
TI  - DOES FATHERS' PRENATAL MENTAL HEALTH BEAR A RELATIONSHIP TO PARENTING STRESS AT 6
      MONTHS?
AB  - This study aimed to explore fathers' mental health and retrospectively reported
      adverse childhood experiences during pregnancy, as well as various pathways
      predicting self-reported stress at 6 months' postpartum as assessed by the
      Parenting Stress Index (PSI; R.R. Abidin, ). A total of 835 fathers contributed
      data to the study. Data collection comprised five time points during pregnancy
      and one at 6 months' postpartum. The main analyses were performed using linear
      regression and path analyses. First, linear regression analyses showed that
      paternal anxiety symptoms during pregnancy predicted stress scores in the PSI
      child domain at 6 months (coefficient = 0.36). Second, path analyses showed that
      depressive symptoms during pregnancy predicted parenting stress in the child
      domain, mediated by spousal disharmony at 6 months' postpartum (coefficient =
      0.77). Third, adverse childhood experiences scores predicted parenting stress in
      the child domain by two different pathways: one mediated by anxiety symptoms in
      pregnancy (coefficient = 0.29) and the other by depressive symptoms in pregnancy
      and experienced spousal disharmony at 6 months' postpartum (coefficient = 0.77).
      The findings suggest that fathers' symptoms of anxiety and depression during
      pregnancy as well as adverse childhood experiences predict paternal stress and a
      negative perception of their children's behavior at 6 months' postpartum.

PMID- 30091798
TI  - Development of a SNP panel for predicting biogeographical ancestry and phenotype
      using massively parallel sequencing.
AB  - Inferring ancestry and physical characteristics of an unknown individual can
      contribute to the direction of the investigation and to clarify the event for
      unknown contributors, cold cases or identification of missing persons and
      disaster victims. The objective of this study is to develop a custom SNP panel on
      massively parallel sequencing devices for predicting the biogeographic ancestry
      and phenotype of an individual. We focused on a two-tier approach to enhance
      ancestry. Our MPS panel contains two ancestry informative SNP (AISNPs) panels
      (i.e., Kidd 55 and SWA panel) to differentiate Southwest Asia from Europe and
      other continental regions. Then we integrated the set of phenotype informative
      SNPs into a set of AISNPs. The final set of 156 SNPs was evaluated on the
      following: sensitivity, genotype concordance, mixtures, ancestry assignment, and
      phenotype prediction. SNP rs6599400 had consistently poor performance and was
      removed from further analyses. The extreme mixture (1:10) was difficult to
      interpret for minor contributor. Ancestry assignment and phenotype predictions
      (for eye, hair and skin) were accurate for samples' population origin. The
      results show that the developed panel provides high coverage data that can be
      used for inferring ancestry and predicting eye, hair, and skin color from the
      intermediate population regions.

PMID- 30091799
TI  - Stimuli-Responsive Ruthenium-Containing Polymers.
AB  - Ruthenium-containing polymers (RCPs) are a type of functional metallopolymer.
      Stimuli-responsive RCPs in which the responsive behaviors derive from the
      structure variation of Ru complexes are reviewed in this Feature Article, with
      particular focus on redox responsive RCPs and photoresponsive RCPs. On the basis
      of the recent progress, the response principle, syntheses, structures,
      properties, applications, and remaining challenges of such stimuli-responsive
      RCPs are discussed.

PMID- 30091800
TI  - Optimization of extraction and analytical protocol for mass spectrometry-based
      metabolomics analysis of hepatotoxicity.
AB  - Drug-induced liver injury is a clinically leading side-effect of drugs. In the
      present study, a liquid chromatography mass spectrometry-based metabolomics
      protocol was optimized for extraction and analysis of endogenous metabolites from
      liver tissue during hepatotoxicity. Various extraction solutions, resuspension
      solutions, extraction folds and dissolution methods for the supernatant were
      compared using the number of extracted total ions, relative response and relative
      extraction efficiency of targeted metabolites from liver tissue. The polar and
      nonpolar endogenous metabolites associated with liver injury were analyzed by
      hydrophilic interaction chromatography and reversed-phase liquid chromatography
      with UPLC-QTOFMS. The results indicated that extraction with 10-fold 50%
      acetonitrile in water and the supernatant diluted (1:1) with 100% acetonitrile
      rather than resuspension was the optimal extraction protocol. Subsequently, the
      optimized method was able to examine the change in metabolites in mouse liver
      tissue resulting from treatment with a toxic natural product, toosendanin. Taken
      together, the optimized extraction and analytical protocol provides high
      reliability and reproducibility for polar and nonpolar metabolites in liver
      tissue and may be suitable for metabolomics analysis of liver injury induced by
      drugs or chemicals.

PMID- 30091801
TI  - Military and Premilitary Trauma, Attachment Orientations, and Posttraumatic
      Stress Disorder Severity Among Male and Female Veterans.
AB  - Samples in prior studies examining attachment theory in the military have been
      predominantly composed of male combat veterans. Given the rates of sexual trauma
      among female veterans and differences in the association between attachment and
      posttraumatic stress disorder (PTSD) severity for sexual trauma survivors, it was
      necessary to consider the attachment characteristics of veterans within a mixed
      sex sample. Participants were a mixed-sex veteran sample seeking inpatient trauma
      related treatment (N = 469). Using independent samples t tests, we examined sex
      differences in attachment. Consistent with our hypothesis, women reported a
      higher level of attachment anxiety than did men, t(351) = -2.12, p = .034. Women
      also reported a higher level of attachment avoidance, t(351) = -2.44, p = .015.
      Using hierarchical regression, we examined the contribution of attachment anxiety
      and avoidance to PTSD severity, partialing out variance accounted for by
      demographic variables and traumatic experiences. Consistent with our hypotheses,
      attachment avoidance predicted PTSD severity on the Clinician-Administered PTSD
      Scale for DSM-IV (CAPS), beta = .20, p < .001, and the PTSD Checklist-Civilian
      Version (PCL-C), beta = .18, p < .001. Attachment anxiety did not predict CAPS
      severity but did predict PCL-C severity, beta = .11, p = .020. These results
      suggest the association between attachment avoidance and PTSD is not exclusive to
      combat trauma and may apply more generally to the larger veteran population.
      Higher levels of attachment anxiety and avoidance among female veterans
      potentially implicate the presence of greater attachment fearfulness among this
      particular subpopulation of veterans.

PMID- 30091802
TI  - A role for ecophysiology in the 'omics' era.
AB  - Plant Ecophysiology is the study on how Plant Physiology is modulated by the
      environment. This discipline could have benefited greatly from the development of
      the different 'omic' technologies (from genomics to metabolomics). Instead, the
      overall impression is that ecophysiology and 'omics' have developed mostly
      independent each other. Here we provide a literature analysis over the past 20
      years which fully confirms this view. Then, we review a few examples of studies
      in which ecophysiology and 'omics' studies have combined to different extents to
      illustrate the potential benefits from their mutualistic interaction. In
      addition, we debate on the possibilities of working with plants other than
      Arabidopsis, which is illustrated with some examples of fascinating plants from
      extreme environments of the world, what we call the 'sherplants'. Finally, we
      raise a call to both communities (ecophysiology and 'omics') to integrate these
      disciplines to enter an 'ecophysiolomics era' to maximize our understanding about
      plant mechanisms from a multidisciplinary approach.

PMID- 30091803
TI  - LGI3 promotes human keratinocyte differentiation via the Akt pathway.
AB  - Leucine-rich repeat LGI family member 3 (LGI3), a member of the LGI family, is a
      secreted protein that is expressed not only in the brain and adipose tissues, but
      also in various skin cells. We previously reported that LGI3 was secreted after
      exposure to ultraviolet B and promoted the migration of HaCaT human
      keratinocytes. In the present study, we investigated whether LGI3 influences the
      differentiation of keratinocytes. The results show that the expression of
      involucrin, a keratinocyte differentiation marker, was reduced in tissue from
      LGI3-knockout mice. Those results indicate that LGI3 plays an important role in
      keratinocyte differentiation. Therefore, we treated HaCaT cells with LGI3 to
      examine its effect on keratinocyte differentiation. Protein levels of various
      differentiation markers were enhanced by treatment with LGI3. Furthermore,
      expression of differentiation markers was inhibited when keratinocytes were
      transfected with an siRNA for LGI3. LGI3 strongly activated Akt, whereas it had
      no apparent effect on extracellular signal-regulated kinase, p38 mitogen
      activated protein kinase, or the c-Jun N-terminal kinase. A specific inhibitor of
      phosphoinositide 3-kinase, LY294002, reduced LGI3-induced expression of
      differentiation markers in HaCaT cells. Taken together, these results suggest
      that LGI3 promotes keratinocyte differentiation and could be used as a
      therapeutic agent to recover skin barrier function in epidermal barrier
      disruption.

PMID- 30091804
TI  - Nucleophilic-Addition-Initiated Ring Expansion and Selectivity in Anionic
      Fragmentation.
AB  - The expansion of rings into larger ones by a mechanism of anionic fragmentation
      is a potent tool for exploring new structural space in a concise manner. As the
      concept has been known and applied for decades now, going a step further calls
      for selectivity in the production of new scaffolds. In this regard, recent
      results demonstrated promising levels of regio-, dia- and enantioselectivity
      which give impulses to the concept of ring expansion involving the fragmentation
      of anionic species generated from unstrained cycles. Initiated by addition of a
      nucleophile, the energy received in the form of electrons triggered skeletal
      rearrangements of simple starting materials while revealing new stereocenters
      and/or regioisomers. Disrupting the symmetry of smaller rings in some cases, the
      strategy gives access to complex larger rings.

PMID- 30091805
TI  - Comparison of ischaemia-reperfusion-induced acute kidney injury by clamping renal
      arteries, veins or pedicles in anaesthetized rats.
AB  - NEW FINDINGS: What is central question of this study What are the differences
      between a traditional renal pedicle-clamping model of acute kidney injury and
      models with occluded renal artery or vein alone in rats? What is main finding and
      its importance? During renal venous occlusion, transmission of high arterial
      pressure into renal capillaries is likely to have caused the rupture of their
      walls and the occurrence of haemorrhagic congestion that led to higher kidney
      tissue damage and dysfunction than with pedicle and artery clamping. ABSTRACT:
      Animal models of ischaemic acute kidney injury (AKI) are valuable tools, but
      their therapeutic outcomes are not usually translated to humans. Ischaemic AKI in
      murines is mostly induced via renal pedicle clamping, which is different from
      patients with AKI that is due to renal artery hypoperfusion or vein thrombosis.
      This study was designed to compare the traditional pedicle-clamping with artery
      or vein occlusion alone in rat models of bilateral renal ischaemia-reperfusion
      (BIR). Twenty-eight anaesthetized male Sprague-Dawley rats were divided into four
      groups, a sham-operation group and groups that underwent 2 h reperfusion
      following 30 min clamping of renal arteries (BIR-A group), veins (BIR-V group) or
      pedicles (BIR-P group). The levels of epithelial injury in proximal tubules and
      thick ascending limb, intratubular casts and vascular congestion as well as renal
      malondialdehyde were moderately lower in the BIR-A than BIR-P group, while the
      BIR-V group showed much higher degrees of these damages than both these groups
      along with massive haemorrhagic congestion. Accordingly, renal blood flow,
      glomerular filtration, Na+ reabsorption, K+ and urea excretion, free water
      reabsorption and urine osmolality were lower in the BIR-V group than in the BIR-A
      and BIR-P groups, while the BIR-P group had slightly worse renal functional
      disorders than the BIR-A group. It seems that transmission of high arterial
      pressure into renal microvessels during venous occlusion causes rupture of
      capillary walls and haemorrhagic congestion, which leads to intensive kidney
      injury. In conclusion, the differences in renal disturbances induced by artery,
      vein and pedicle clamping strongly suggest use of a proper experimental model for
      each type of human ischaemic AKI.

PMID- 30091806
TI  - Muscle and tendon lengthening behaviour of the medial gastrocnemius during ankle
      joint rotation in children with cerebral palsy.
AB  - NEW FINDINGS: What is the central question of this study? Which structures of the
      medial gastrocnemius muscle-tendon unit contribute to its lengthening during
      joint rotation and thus receive the stretching stimulus? What is the main finding
      and its importance? We show, for the first time, that muscle and tendon lengthen
      in a different manner in children with cerebral palsy compared with typically
      developing children during a similar amount of muscle-tendon unit lengthening or
      joint rotation. This indicates possible differences in mechanical muscle and
      tendon properties attributable to cerebral palsy, which are not evident by
      assessment of muscle function at the level of a joint. ABSTRACT: Children with
      cerebral palsy (CP) commonly present with reduced ankle range of motion (ROM)
      attributable, in part, to changes in mechanical properties of the muscle-tendon
      unit (MTU). Detailed information about how muscle and tendon interact to
      contribute to joint rotation is currently lacking but might provide essential
      information to explain the limited effectiveness of stretching interventions in
      children with CP. The purpose of this study was to quantify which structures
      contribute to MTU lengthening and thus receive the stretch during passive ankle
      joint rotation. Fifteen children with CP (age, in mean +/- SD, 11.4 +/- 3 years)
      and 16 typically developing (TD) children (age, in mean +/- SD, 10.2 +/- 3 years)
      participated. Ultrasound was combined with motion tracking, joint torque and EMG
      to record fascicle, muscle and tendon lengthening of the medial gastrocnemius
      during passive ankle joint rotations over the full ROM and a common ROM. In
      children with CP, relative to MTU lengthening, muscle and fascicles lengthened
      less (CP, 50.4% of MTU lengthening; TD, 63% of MTU lengthening; P < 0.04) and
      tendon lengthened more (CP, 49.6% of MTU lengthening; TD, 37% of MTU lengthening;
      P < 0.01) regardless of the ROM studied. Differences between groups in the amount
      of lengthening of the underlying structures during a similar amount of joint
      rotation and MTU displacement indicate possible differences in tissue mechanical
      properties attributable to CP, which are not evident by assessment at the level
      of a joint. These factors should be considered when assessing and treating muscle
      function in children with CP, for example during stretching exercises, because
      the muscle might not receive much of the applied lengthening stimulus.

PMID- 30091807
TI  - Semimetal-Semiconductor Transitions for Monolayer Antimonene Nanosheets and Their
      Application in Perovskite Solar Cells.
AB  - Antimonene-based 2D materials are attracting increasing research interest due to
      their superior physicochemical properties and promising applications in next
      generation electronics and optoelectronics devices. However, the semiconductor
      properties of antimonene are still at the theoretical simulation stage and are
      not experimentally verified, significantly restricting its applications in
      specific areas. In this study, the semiconductor properties of monolayer
      antimonene nanosheets are experimentally verified. It is found that the obtained
      semiconductive antimonene nanosheets (SANs) exhibit indirect bandgap properties,
      with photoluminescence (PL) bandgap at about 2.33 eV and PL lifetime of 4.3 ns.
      Moreover, the obtained SANs are ideal for the hole extraction layer in planar
      inverted perovskite solar cells (PVSCs) and significantly enhance the device
      performance due to fast hole extraction and efficient hole transfer at the
      perovskite/hole transport layer interface. Overall, these findings look promising
      for the future prospects of antimonene in electronics and optoelectronics.

PMID- 30091808
TI  - Amphetamines for attention deficit hyperactivity disorder (ADHD) in adults.
AB  - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset
      disorder characterised by inattention, hyperactivity, and impulsivity. ADHD can
      persist into adulthood and can affects individuals' social and occupational
      functioning, as well as their quality of life and health. ADHD is frequently
      associated with other mental disorders such as substance use disorders and
      anxiety and affective disorders. Amphetamines are used to treat adults with ADHD,
      but uncertainties about their efficacy and safety remain. OBJECTIVES: To examine
      the efficacy and safety of amphetamines for adults with ADHD. SEARCH METHODS: In
      August 2017, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases,
      and two trials registers, and we ran citation searches for included studies. We
      also contacted the corresponding authors of all included studies, other experts
      in the field, and the pharmaceutical company, Shire, and we searched the
      reference lists of retrieved studies and reviews for other published,
      unpublished, or ongoing studies. For each included study, we performed a citation
      search in Web of Science to identify any later studies that may have cited it.
      SELECTION CRITERIA: We searched for randomised controlled trials comparing the
      efficacy of amphetamines (at any dose) for ADHD in adults aged 18 years and over
      against placebo or an active intervention. DATA COLLECTION AND ANALYSIS: Two
      review authors extracted data from each included study. We used the standardised
      mean difference (SMD) and the risk ratio (RR) to assess continuous and
      dichotomous outcomes, respectively. We conducted a stratified analysis to
      determine the influence of moderating variables. We assessed trials for risk of
      bias and drew a funnel plot to investigate the possibility of publication bias.
      We rated the quality of the evidence using the GRADE approach, which yielded
      high, moderate, low, or very low quality ratings based on evaluation of within
      trial risk of bias, directness of evidence, heterogeneity of data; precision of
      effect estimates, and risk of publication bias. MAIN RESULTS: We included 19
      studies that investigated three types of amphetamines: dexamphetamine (10.2 mg/d
      to 21.8 mg/d), lisdexamfetamine (30 mg/d to 70 mg/d), and mixed amphetamine salts
      (MAS; 12.5 mg/d to 80 mg/d). These studies enrolled 2521 participants; most were
      middle-aged (35.3 years), Caucasian males (57.2%), with a combined type of ADHD
      (78.8%). Eighteen studies were conducted in the USA, and one study was conducted
      in both Canada and the USA. Ten were multi-site studies. All studies were placebo
      controlled, and three also included an active comparator: guanfacine, modafinil,
      or paroxetine. Most studies had short-term follow-up and a mean study length of
      5.3 weeks.We found no studies that had low risk of bias in all domains of the
      Cochrane 'Risk of bias' tool, mainly because amphetamines have powerful
      subjective effects that may reveal the assigned treatment, but also because we
      noted attrition bias, and because we could not rule out the possibility of a
      carry-over effect in studies that used a cross-over design.Sixteen studies were
      funded by the pharmaceutical industry, one study was publicly funded, and two
      studies did not report their funding sources.Amphetamines versus placeboSeverity
      of ADHD symptoms: we found low- to very low-quality evidence suggesting that
      amphetamines reduced the severity of ADHD symptoms as rated by clinicians (SMD 
      0.90, 95% confidence interval (CI) -1.04 to -0.75; 13 studies, 2028 participants)
      and patients (SMD -0.51, 95% CI -0.75 to -0.28; six studies, 120
      participants).Retention: overall, we found low-quality evidence suggesting that
      amphetamines did not improve retention in treatment (risk ratio (RR) 1.06, 95% CI
      0.99 to 1.13; 17 studies, 2323 participants).Adverse events: we found that
      amphetamines were associated with an increased proportion of patients who
      withdrew because of adverse events (RR 2.69, 95% CI 1.63 to 4.45; 17 studies,
      2409 participants).Type of amphetamine: we found differences between amphetamines
      for the severity of ADHD symptoms as rated by clinicians. Both lisdexamfetamine
      (SMD -1.06, 95% CI -1.26 to -0.85; seven studies, 896 participants; low-quality
      evidence) and MAS (SMD -0.80, 95% CI -0.93 to -0.66; five studies, 1083
      participants; low-quality evidence) reduced the severity of ADHD symptoms. In
      contrast, we found no evidence to suggest that dexamphetamine reduced the
      severity of ADHD symptoms (SMD -0.24, 95% CI -0.80 to 0.32; one study, 49
      participants; very low-quality evidence). In addition, all amphetamines were
      efficacious in reducing the severity of ADHD symptoms as rated by patients
      (dexamphetamine: SMD -0.77, 95% CI -1.14 to -0.40; two studies, 35 participants;
      low-quality evidence; lisdexamfetamine: SMD -0.33, 95% CI -0.65 to -0.01; three
      studies, 67 participants; low-quality evidence; MAS: SMD -0.45, 95% CI -1.02 to
      0.12; one study, 18 participants; very low-quality evidence).Dose at study
      completion: different doses of amphetamines did not appear to be associated with
      differences in efficacy.Type of drug-release formulation: we investigated
      immediate- and sustained-release formulations but found no differences between
      them for any outcome.Amphetamines versus other drugsWe found no evidence that
      amphetamines improved ADHD symptom severity compared to other drug interventions.
      AUTHORS' CONCLUSIONS: Amphetamines improved the severity of ADHD symptoms, as
      assessed by clinicians or patients, in the short term but did not improve
      retention to treatment. Amphetamines were associated with higher attrition due to
      adverse events. The short duration of studies coupled with their restrictive
      inclusion criteria limits the external validity of these findings. Furthermore,
      none of the included studies had an overall low risk of bias. Overall, the
      evidence generated by this review is of low or very low quality.

PMID- 30091809
TI  - Survival after the diagnosis of de novo malignancy in liver transplant
      recipients.
AB  - In the setting of liver transplant (LT), the survival after the diagnosis of de
      novo malignancies (DNMs) has been poorly investigated. In this study, we assessed
      the impact of DNMs on survival of LT recipients as compared to corresponding LT
      recipients without DNM. A nested case-control study was conducted in a cohort of
      2,818 LT recipients enrolled in nine Italian centres between 1985 and 2014. Cases
      were 244 LT recipients who developed DNMs after LT. For each case, two controls
      matched for gender, age, and year at transplant were selected by incidence
      density sampling among cohort members without DNM. The survival probabilities
      were estimated using the Kaplan-Meier method. Hazard ratios (HRs) of death and
      95% confidence intervals (CIs) were estimated using Cox proportional hazard
      models. The all-cancer 10-year survival was 43% in cases versus 70% in controls
      (HR = 4.66; 95% CI: 3.17-6.85). Survival was impaired in cases for all the most
      frequent cancer types, including lung (HR = 37.13; 95% CI: 4.98-276.74), non
      Hodgkin lymphoma (HR = 6.57; 95% CI: 2.15-20.01), head and neck (HR = 4.65; 95%
      CI: 1.81-11.95), and colon-rectum (HR = 3.61; 95% CI: 1.08-12.07). The survival
      gap was observed for both early and late mortality, although the effect was more
      pronounced in the first year after cancer diagnosis. No significant differences
      in survival emerged for Kaposi's sarcoma and nonmelanoma skin cancers. The
      survival gap herein quantified included a broad range of malignancies following
      LT and prompts close monitoring during the post-transplant follow-up to ensure
      early cancer diagnosis and to improve survival.

PMID- 30091810
TI  - Favorable efficacy of glecaprevir plus pibrentasvir as salvage therapy for HCV
      failures to prior direct-acting antivirals regimens.
AB  - In real-world settings, not much information is probably available on the
      treatment efficacy of the combination of glecaprevir and pibrentasvir (G/P) as a
      salvage therapy in failures of prior direct-acting antiviral (DAA) regimens.
      Especially, the evolution of NS5A resistance-associated variants (RAVs) and
      treatment efficacy in patients who received G/P for failures of prior treatment
      more than once is unknown. Twenty patients, who were exposed to glecaprevir 300
      mg/d and pibrentasvir 120 mg/d for 12 weeks in failures of prior DAAs regimens
      were evaluated for sustained virological response at 12 weeks after the end of
      treatment (SVR12). The overall rate of SVR12 was 100%, based on intention-to
      treat analysis. Five patients infected with genotype 1b, who received G/P for
      failures of prior treatment more than once, were analyzed for the evolution of
      RAVs in NS5A region. All of the five patients exhibited SVR12, regardless of the
      numbers of times of prior treatment (more than once), prior treatment response
      (nonresponse), and fibrosis stage (FIB-4 index >= 3.25). At the commencement of
      G/P, all five patients were detected with NS5A RAVs at the position of aa 93.
      Four patients, except for one, were detected with RAVs at both positions of aa 31
      and aa 93 (double mutation). All patients could achieve SVR12 with G/P,
      regardless of the emergence of NS5A RAVs, accompanied by failure to prior NS5A
      regimens more than once. In conclusion, our study indicated that G/P was a
      potentially useful salvage treatment for patients who failed prior DAAs regimens
      more than once.

PMID- 30091811
TI  - Resting-state pulvinar-posterior parietal decoupling in PTSD and its dissociative
      subtype.
AB  - Key evidence points toward alterations in the neurocircuitry of large-scale
      networks among patients with posttraumatic stress disorder (PTSD). The pulvinar
      is a thalamic region displaying reciprocal connectivity with the cortex and has
      been shown to modulate alpha synchrony to facilitate network communication.
      During rest, the pulvinar displays functional connectivity with the posterior
      parietal cortex (PPC), a heteromodal network of brain areas underlying
      multisensory integration and socioaffective functions that are shown at deficit
      in PTSD. Accordingly, this study seeks to reveal the resting-state functional
      connectivity (rsFC) patterns of individuals with PTSD, its dissociative subtype
      (PTSD + DS) and healthy controls. A whole-brain rsFC analysis was conducted using
      SPM12 and PickAtlas. Connectivity was analyzed for the left and right pulvinar
      across groups of individuals with PTSD (n = 81), PTSD + DS (n = 49), and controls
      (n = 51). As compared to PTSD, controls displayed significantly greater pulvinar
      rsFC with the superior parietal lobule and precuneus. Moreover, as compared to
      PTSD + DS, controls showed increased pulvinar connectivity with the superior
      parietal lobule, inferior parietal lobule and the precuneus. PTSD groups did not
      display stronger connectivity with any region as compared to controls. Last, PTSD
      had greater rsFC in the supramarginal gyrus relative to PTSD + DS. Reduced
      connectivity between the pulvinar and PPC may explain impairments to
      autobiographical memory, self-referential processing, and socioaffective domains
      in PTSD and PTSD + DS even at "rest." Critically, these alterations appear to be
      exacerbated in individuals with PTSD + DS, which may have important implications
      for treatment.

PMID- 30091812
TI  - Assessing recrudescence of photoregressed Siberian hamster ovaries using in vitro
      whole ovary culture.
AB  - In vitro culture has been used to study different aspects of ovarian function;
      however, this technique has not been applied to study recrudescence, or the
      return of ovarian function in seasonally breeding species. In Siberian hamsters,
      exposure to inhibitory photoperiods induces declines in ovarian function, which
      are restored with photostimulation. Because these changes are mediated by changes
      in systemic gonadotropin (GT) secretion, we hypothesized that culturing
      photoregressed ovaries with GT would restore aspects of function and induce
      expression of key folliculogenic factors. Adult female Siberian hamsters were
      exposed to either long-day (LD; 16L:8D) or short-day (SD; 8L:16D) photoperiods
      for 14 weeks to maintain in vivo cyclicity or induce gonadal regression,
      respectively. Isolated ovaries were then cultured for 10 days with or without GT.
      Ovarian mass and messenger RNA (mRNA) expression of mitotic marker Pcna were
      increased in cultured SD ovaries (cSD) ovaries with GT as compared to without GT,
      with no changes noted among cultured LD (cLD) ovaries. Media estradiol and
      progesterone concentrations increased in both cLD and cSD ovaries cultured with
      GT as compared to without GT. No differences in follicle numbers or incidence of
      apoptosis were noted across groups. In addition, differential mRNA expression of
      folliculogenic growth factors ( Bmp-4, Ntf-3, Inh-alpha, Gdf-9, Igf-1, Has-2, and
      Cox-2) was observed in cSD treated with or without GT. Together, these results
      suggest that this in vitro model could be a useful tool to (a) study the return
      of function in photoregressed ovaries, and (b) to identify the specific roles
      folliculogenic factors play in ovarian recrudescence.

PMID- 30091813
TI  - One-Pot Synthesis of Block Copolymers by a Combination of Living Cationic and
      Controlled Radical Polymerization.
AB  - The reversible addition-fragmentation chain-transfer (RAFT) process represents a
      sophisticated polymerization technique for the preparation of tailored and well
      defined polymers from acrylates, acrylamides, and (meth)acrylates. The direct
      switching from other methods, such as cationic polymerizations, without the need
      for tedious functionalization and purification steps remains challenging. Within
      this study, it is demonstrated that poly(2-oxazoline) (P(Ox)) macro chain
      transfer agents (macro-CTAs) can be prepared through the quenching of the
      cationic ring-opening polymerization with a carbonotrithioate salt. The end
      functionalization of the P(Ox)s is observed to be almost quantitative and the
      macro-CTAs could be directly used for RAFT polymerization without further
      purification. This one-pot procedure could be extended to a variety of
      (multi)block copolymers consisting of different 2-oxazolines and acrylates with
      good-to-excellent control. Kinetic studies revealed the controlled polymerization
      of block copolymers, which are further accessible for alpha- and omega-end
      functionalization. The simplicity and versatility of the approach promise a
      straightforward access to block copolymers from cationic and controlled radical
      polymerizations.

PMID- 30091814
TI  - Cognitive functioning and treatment outcomes in a randomized controlled trial of
      internet-delivered drug and alcohol treatment.
AB  - BACKGROUND AND OBJECTIVES: Substance use disorders are associated with lower
      cognitive functioning, and this impairment is associated with poorer outcomes.
      The Therapeutic Education System (TES) is an internet-based psychosocial
      intervention for substance use disorders that may provide enhanced treatment for
      individuals with cognitive deficits. This secondary analysis investigates the
      association between cognitive functioning and treatment outcomes in a large (N =
      507) randomized controlled effectiveness trial of TES compared to treatment-as
      usual conducted within outpatient programs in the National Drug Abuse Treatment
      Clinical Trials Network. METHODS: All participants completed a computer-based
      cognitive assessment (MicrocogTM short version) at baseline. Scores on subtests
      of attention, reasoning, and spatial perception were tested as moderators of the
      treatment effect on abstinence and retention at the end of the 12-week treatment
      phase using mixed effects logistic regression. RESULTS: Cognitive functioning was
      not found to be a moderator of treatment on abstinence or retention. Post-hoc
      analysis of the main effect of cognitive functioning on retention and abstinence
      found impaired reasoning and cognitive flexibility were associated with lower
      retention. There were no other main effects of cognitive functioning on retention
      or abstinence. CONCLUSIONS: The benefit of internet delivered treatment over
      standard care was unchanged across a range of cognitive functioning. Consistent
      with previous research, mild to moderate impairment in reasoning and cognitive
      flexibility were associated with lower retention across both treatment arms.
      SCIENTIFIC SIGNIFICANCE: An internet-delivered cognitive behavioral intervention
      for substance use disorders, TES, is equally effective across a spectrum of
      cognitive functioning among diverse patients. (Am J Addict 2018;27:509-515).

PMID- 30091816
TI  - Controlling Nanomaterial Size and Shape for Biomedical Applications via
      Polymerization-Induced Self-Assembly.
AB  - Rapid developments in the polymerization-induced self-assembly (PISA) technique
      have paved the way for the environmentally friendly production of nanoparticles
      with tunable size and shape for a diverse range of applications. In this feature
      article, the biomedical applications of PISA nanoparticles and the substantial
      progress made in controlling their size and shape are highlighted. In addition to
      early investigations into drug delivery, applications such as medical imaging,
      tissue culture, and blood cryopreservation are also described. Various parameters
      for controlling the morphology of PISA nanoparticles are discussed, including the
      degree of polymerization of the macro-CTA and core-forming polymers, the
      concentration of macro-CTA and core-forming monomers, the solid content of the
      final products, the solution pH, the thermoresponsitivity of the macro-CTA, the
      macro-CTA end group, and the initiator concentration. Finally, several
      limitations and challenges for the PISA technique that have been recently
      addressed, along with those that will require further efforts into the future,
      will be highlighted.

PMID- 30091815
TI  - Block Copolymers by Mechanistic Transformation from PROAD to Iniferter Process.
AB  - A facile strategy for synthesizing block copolymers by the combination of two
      different living polymerization techniques, namely, photoinduced radical
      oxidation/addition/deactivation (PROAD) and iniferter processes is described. In
      the first step, PROAD polymerization of isobutyl vinyl ether using
      bromotriphenylmethane, dimanganese decacarbonyl (Mn2 (CO)10 ), and
      diphenyliodonium bromide (Ph2 I+ Br- ) is carried out to yield polymers with
      triphenylmethyl (trityl) end groups. These prepolymers are used as
      macroiniferters in thermally induced free radical polymerization of vinyl
      monomers such as methyl methacrylate, tert-butyl acrylate, and styrene, resulting
      in the formation of corresponding block copolymers free from homopolymers. The
      precursor polymer and final block copolymers are characterized by 1 H NMR, FT-IR,
      GPC, and DSC analyses.

PMID- 30091817
TI  - TBD-Catalyzed Ring-Opening Polymerization of Alkyl-Substituted Morpholine-2,5
      Dione Derivatives.
AB  - In a two-step synthesis, five different alkyl-substituted morpholine-2,5-dione
      monomers were synthesized from the natural amino acids glycine, alanine, valine,
      leucine, and isoleucine. The heterocyclic compounds crystallize in a boat-like
      conformation and are polymerized via 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD)
      catalyzed ring-opening polymerization (ROP) in tetrahydrofuran. Well-defined
      polymers could be obtained from the monomers based on valine, leucine, and
      isoleucine at a feed ratio of M/I/TBD = 100/1/0.5. Kinetic studies of the ROP
      reveal that the molar masses and dispersities (D < 1.2) could be well controlled,
      as confirmed by size exclusion chromatography and 1 H NMR spectroscopy. At
      conversions above 50%, the polymerization rate decreases and the dispersity
      slightly increases, presumably due to transesterification. Matrix-assisted laser
      desorption time-of-flight mass spectrometry indicates the presence of polymer
      chains with alpha-end groups derived from the initiator.

PMID- 30091818
TI  - A Homoleptic KrF2 Complex, [Hg(KrF2 )8 ][AsF6 ]2 ?2 HF.
AB  - The reaction of Hg(AsF6 )2 with a large molar excess of KrF2 in anhydrous HF has
      afforded the first homoleptic KrF2 coordination complex of a metal cation,
      [Hg(KrF2 )8 ][AsF6 ]2 ?2 HF. The [Hg(KrF2 )8 ]2+ dication is well-isolated in the
      low-temperature crystal structure of its HF-solvated [AsF6 ]- salt, and consists
      of eight KrF2 molecules that are terminally coordinated to Hg2+ by means of Hg
      F(KrF) bonds to form a slightly distorted, square-antiprismatic coordination
      sphere around mercury. The Raman spectrum of [Hg(KrF2 )8 ]2+ was assigned with
      the aid of calculated gas-phase vibrational frequencies. Computational studies
      indicate that both electrostatic and orbital interactions are important for metal
      ligand bonding and provide insight into the geometry of the [Hg(KrF2 )8 ]2+
      cation and the nature of noble-gas difluoride ligand bonding.

PMID- 30091819
TI  - Fingerprinting Biogenic Aldehydes through Pattern Recognition Analyses of
      Excitation-Emission Matrices.
AB  - Biogenic carbonyls, especially aldehydes, have previously demonstrated their
      potential to serve as early diagnostic biomarkers for disease and injury that
      have not been fully realized owing, in part, to the lack of a rapid and simple
      point-of-care method for aldehyde identification. The ability to determine which
      carbonyl compound is elevated and not just the total aldehydic load may provide
      more disease- or injury-specific diagnostic information. Toward this end, a novel
      fluorophore is presented that is able to form a complex with biogenic carbonyls
      under catalyst-free conditions so as to give a fluorescent fingerprint of the
      resulting hydrazone. The successful identification of bound carbonyls was
      accomplished with a newly described algorithm that applied principal curvature
      analysis of excitation-emission matrices to reduce surface features to ellipse
      representations, followed by a pattern-matching routine. With this algorithm,
      carbonyls were identified over a range of concentrations, and mixture components
      were successfully parsed. Overall, the results presented lay the groundwork for
      novel implementations of chemometrics to low-cost, rapid, and simple-to-implement
      point-of-care diagnostics.

PMID- 30091820
TI  - The circadian gene, Per2, influences methamphetamine sensitization and reward
      through the dopaminergic system in the striatum of mice.
AB  - Drug addiction is a chronic and relapsing brain disorder, influenced by complex
      interactions between endogenous and exogenous factors. Per2, a circadian gene,
      plays a role in drug addiction. Previous studies using Per2-knockout mice have
      shown a role for Per2 in cocaine, morphine and alcohol addiction. In the present
      study, we investigated the role of Per2 in methamphetamine (METH) addiction using
      Per2-overexpression and knockout mice. We observed locomotor sensitization
      responses to METH administration, and rewarding effects using a conditioned place
      preference test. In addition, we measured expression levels of dopamine and
      dopamine-related genes (monoamine oxidase A, DA receptor 1, DA receptor 2, DA
      active transporter, tyrosine hydroxylase and cAMP response element-binding
      protein 1) in the striatum of the mice after repeated METH treatments, using qRT
      PCR. Per2-overexpressed mice showed decreased locomotor sensitization and
      rewarding effects of METH compared to the wildtype mice, whereas the opposite was
      observed in Per2 knockout mice. Both types of transgenic mice showed altered
      expression levels of dopamine-related genes after repeated METH administration.
      Specifically, we observed lower dopamine levels in Per2-overexpressed mice and
      higher levels in Per2-knockout mice. Taken together, Per2 expression levels may
      influence the addictive effects of METH through the dopaminergic system in the
      striatum of mice.

PMID- 30091821
TI  - Neurovascular sparing during anterior resections for diverticular disease: the
      century-long debate.

PMID- 30091822
TI  - Real-world comparative analysis of bleeding complications and health-related
      quality of life in patients with haemophilia A and haemophilia B.
AB  - INTRODUCTION: Clinical severity and impact of haemophilia on quality of life have
      been generally considered to be lower for haemophilia B (HB) compared with
      haemophilia A (HA) patients. AIMS: To compare annual bleeding rate (ABR), target
      joint development and health-related quality of life (HRQoL) between adult (>=18
      years) severe HA and HB patients using recent data from the Cost of Haemophilia
      in Europe: a Socioeconomic Survey (CHESS) study. METHODS: Multivariate
      generalized linear models (GLM) were constructed to assess the relationship
      between haemophilia type, ABR, HRQoL (derived from EQ-5D index scores) and the
      presence of target joints while controlling for covariates. RESULTS: Of the 1225
      patients included, 77% (n = 949) had HA and 23% (n = 278) had HB. Of the 514
      patients who completed the EQ-5D, 78% (n = 405) had HA, and 22% (n = 110) had HB.
      Unadjusted mean ABR was 3.79 in HA and 4.60 in HB. The presence of >=1 target
      joint was reported in 59% and 54% of patients with HA and HB, respectively.
      Unadjusted mean EQ-5D index score was 0.78 in HA and 0.76 in HB. Haemophilia type
      was not a significant predictor of ABR, target joints or HRQoL when adjusted for
      confounding factors such as BMI, age and replacement therapy regimen. CONCLUSION:
      Data suggest comparable ABR, incidence of target joints and HRQoL between
      patients with HB and HA indicating comparable clinical severity and disease
      impact on patient quality of life.

PMID- 30091823
TI  - Craving, cortisol and behavioral alcohol motivation responses to stress and
      alcohol cue contexts and discrete cues in binge and non-binge drinkers.
AB  - Alcohol use disorders are associated with high craving and disruption of stress
      biology, but their role in behavioral alcohol motivation is less clear. We
      examined the effects of craving and cortisol responses on behavioral alcohol
      motivation to stress, alcohol cue and neutral-relaxing context cues, in addition
      to discrete alcohol cues, in demographically matched binge/heavy (BH) and
      moderate (MD) social drinkers. Subjects participated in a 3-day laboratory
      experiment of provocation by three personalized guided imagery contexts and
      discrete alcohol cues followed by the 'alcohol taste test' (ATT) to assess
      behavioral motivation, as measured by ATT intake. Post-ATT alcohol effects on
      craving and cortisol responses were also examined. Results indicate BH consumed
      significantly more alcohol than MD in the ATT. Stress and alcohol cue contexts,
      relative to neutral, led to significantly greater ATT intake across both groups,
      which also correlated positively with self-reported alcohol use in past 30 days.
      Stress and alcohol context and discrete alcohol cues each significantly increased
      alcohol craving, more so in the BH than MD, and significantly predicted greater
      ATT intake in BH only. The BH showed significantly lower cortisol responses than
      MD overall and blunted cortisol responses to cues predicted significantly greater
      ATT intake in the stress condition for BH and in the alcohol cue condition for
      MD. Higher ATT intake predicted greater cortisol response and higher craving post
      ATT, and these effects were moderated by group status. In sum, findings suggest a
      role for sensitized context-induced craving and blunted cortisol responses in
      increased behavioral motivation for alcohol.

PMID- 30091824
TI  - Vascularized composite allotransplantation in the United States: A descriptive
      analysis of the Organ Procurement and Transplantation Network Data.
AB  - On July 3, 2014, the Organ Procurement and Transplantation Network/United Network
      for Organ Sharing was charged with the oversight of vascularized composite
      allograft (VCA) procurement and transplantation in the United States. As of
      December 31, 2017, 61 VCA programs at 27 centers were approved in the United
      States. Fifty candidates have been added to the waiting list at 15 centers.
      Twenty-eight VCA transplants have been performed at 14 programs (10 upper limb,
      10 uterus, 5 craniofacial, 1 scalp, 1 abdominal wall, and 1 penile). Twenty-two
      VCAs were procured from 21 deceased donors, resulting in 109 non-VCA organs
      transplanted (15 hearts, 3 intestine, 40 kidney, 20 livers, 24 lungs, and 7
      pancreata). Six uterus transplants were performed from living donors. Fourteen
      candidates were still waiting at 9 centers on December 31, 2017. Two of the 10
      uterus recipients had live births and 3 still had viable grafts. Seventeen of 18
      nonuterus recipients had functioning grafts. At present, VCA is an emerging field
      with a small number of patients transplanted. Data on posttransplant survival and
      functional outcomes continue to be collected to further the understanding of this
      complex and evolving field. Further systematic data are important for policy
      refinement and assurance of patient safety.

PMID- 30091825
TI  - Variations of antibiotic resistance profiles in chickens during administration of
      amoxicillin, chlortetracycline and florfenicol.
AB  - AIM: To assess the effect of antibiotics administered in feed on the resistance
      phenotypes and genotypes of Escherichia coli in the chicken intestine. METHOD AND
      RESULTS: Chickens were administered amoxicillin, chlortetracycline and
      florfenicol in feed and 203 intestinal E. coli were examined for their
      susceptibility to 11 antimicrobial agents and for the presence of antibiotic
      resistance genes (ARG) using PCR. DNA was extracted from chicken stool samples in
      15, 20, 30 and 40 day old chickens. We found that while antibiotic resistance
      rates increased with time, the relative gene abundance of tet(W), tet(A), cmlA,
      cfr and sul1 decreased. In contrast, the relative abundance of gene blaTEM and
      mcr-1 increased over the experimental period. Pearson correlation analysis
      indicated that sul1 was correlated with tet(W) (R = 0.630, P < 0.01) and cmlA was
      correlated with cfr (R = 0.587, P < 0.01). Interestingly, mcr-1 correlated with
      tet(W) (R = -0.546, P < 0.05). CONCLUSIONS: Administration of different
      antibiotic reduced the relative abundance of ARG in chickens but did not halt the
      expansion of antibiotic resistance. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Changing the pattern of antibiotic types used to prevent antibiotic resistance in
      chickens is not a viable method to prevent the spread of ARG.

PMID- 30091827
TI  - Soluble Hyperbranched Porous Organic Polymers.
AB  - Soluble porous organic polymers (SPOPs) are currently the subject of extensive
      investigation due to the enhanced processability compared to insoluble
      counterparts. Here, a new concept for the construction of SPOPs is presented,
      which combines the unique topological structure of hyperbranched polymers with
      rigid building blocks. By using this facile, one-step strategy, a class of novel
      SPOPs which possess surface areas up to 646 m2 g-1 have been synthesized. The
      extended pi-conjugated backbone affords the polymers bright fluorescence under UV
      irradiation. Interestingly, after dissolution in a suitable solvent that was
      slowly evaporated, the polymers retain a large extent of porosity. The SPOPs are
      potential candidates for gas storage and separation, photovoltaic, and biological
      applications. In particular, due to the presence of an internal porous structure
      and open conformations, they show high drug loading efficiency (1.91 g of
      ibuprofen per gram), which is considerably higher than conventional porous
      organic polymers.

PMID- 30091826
TI  - Diet and other environmental factors shape the bacterial communities of fish gut
      in an eutrophic lake.
AB  - AIMS: The aim of this work was to study the gut microbial diversity from eight
      species of wild fish with different feeding habits, digestive physiology (gastric
      vs agastric) and provide comparative structural analysis of the microbial
      communities within their environment (food items, water, sediments and
      macrophytes). METHODS AND RESULTS: The microbiota of fish gut and their prey
      items were studied using next generation high-throughput sequencing of the 16S
      ribosomal RNA genes. A scatter plot based on PCoA scores demonstrated the
      microbiota formed three groups: (i) stomach and intestinal mucosa (IM), (ii)
      stomach and intestinal content (IC), and (iii) prey and environment. Comparisons
      using ANOSIM showed significant differences among IC of omnivorous,
      zoobenthivorous, zooplanktivorous-piscivorous fishes (P <= 0.1). No significant
      difference was detected for mucosa from the same groups (P > 0.1). CONCLUSIONS:
      Neither the interspecies differences in fish diet nor their phylogenetic position
      had any effect on the microbiome of the IM, but diet did influence the
      composition of the microbiota of the IC. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The data demonstrate that fish harboured specific groups of bacteria that do not
      completely reflect the microbiota of the environment or prey.

PMID- 30091828
TI  - Extended Periprostatic Nerve Distributions on The Prostate Surface Confirmed
      using Diffusion Tensor Imaging (DTI).
AB  - OBJECTIVE: To perform descriptive microscopic study of prostatectomy specimens
      from 19 patients which anatomically characterizes distributions of periprostatic
      nerves qualities and visualize them using diffusion tensor imaging (DTI). METHODS
      AND MATERIALS: Serial whole-mounted sections were stained for cholinergic(nNOS),
      adrenergic(TH), and sensory(CGRP) nerves. Extracapsular stained nerves were
      counted by prostate surface sector and classified by diameter. Stain-related
      relative density was calculated and distribution patterns were evaluated. To
      better visualize the reported neuronal structures and independently confirm our
      findings, nerve concordance in five male volunteers was investigated using a 3
      Tesla-MRI-DTI system. RESULTS: At the base, cholinergic nerves were distributed
      from the anterolateral to posterior sectors, continuing posterolaterally
      (midsection) into the posterolateral-posterior sector toward the apex. Adrenergic
      nerves were distributed across the anterolateral-posterior sectors at the base,
      with the course narrowing to the posterolateral-posterior sectors at the mid and
      apical levels. Sensory fibers were found posterolaterally-posteriorly at the
      base, continuing posterolaterally over the mid and apical levels. Although it was
      not possible to determine the different nerve qualities, DTI confirmed histologic
      findings from the base to the apex. CONCLUSION: Different types of nerve fibers
      demonstrate distribution variations. When linked to possible functional aspects
      of the different nerve types, this morphologic evidence may be of importance to
      further protect function after radical prostatectomy. To our knowledge this is
      the first time that DTI confirmed reported histological findings in nerve sparing
      radical prostatectomies. DTI could be used as an important tool to correlate
      nerves-to-tumor for better pre-operative planning and incorporate imaging into
      the treatment. This article is protected by copyright. All rights reserved.

PMID- 30091829
TI  - Enantioselective Construction of Tertiary Boronic Esters by Conjunctive Cross
      Coupling.
AB  - Catalytic enantioselective conjunctive cross-coupling has been developed to
      construct tertiary alkylboronic esters. These reactions occur with good yield and
      enantioselectivity for a range of substrates. Mechanistic experiments reveal
      aspects of the catalytic cycle that allow hindered substrates to react without
      significant complicating side reactions.

PMID- 30091831
TI  - Nausicaa suture for placenta accreta spectrum: further studies are needed.

PMID- 30091830
TI  - Sirtuin3 protects aged human mesenchymal stem cells against oxidative stress and
      enhances efficacy of cell therapy for ischaemic heart diseases.
AB  - Sirtuin3 (SIRT3) is associated with oxidative stress and lifespan. However, the
      possible mechanisms underlying its influence are unknown. We hypothesized that
      SIRT3 increases the antioxidant capacity of aged cells and improves the efficacy
      of human mesenchymal stem cell (hMSC) therapy for ischaemic heart diseases in
      aged patients. In vitro, the antioxidant capacity of old hMSCs (O-hMSCs) was
      increased after SIRT3 overexpression using a gene transfection technique, while
      the antioxidant capacity of young hMSCs (Y-hMSCs) was decreased by SIRT3
      silencing. The levels of forkhead box O3a (FoxO3a) in the nucleus, and
      antioxidant enzymes Mn-superoxide dismutase (MnSOD) and catalase (CAT) increased
      in SIRT3-overexpressed O-hMSCs while they decreased in SIRT3-silenced Y-hMSCs
      after oxidative stress. Following myocardial infarction in adult rats in vivo,
      infarct size decreased and cardiac function was significantly enhanced after cell
      transplantation with SIRT3 overexpressed O-hMSCs. The number of apoptotic cells
      decreased and the survival rate of transplanted cells increased following SIRT3
      overexpression in O-hMSCs. SIRT3 protects aged hMSCs against oxidative stress by
      positively regulating antioxidant enzymes (MnSOD and CAT) via increasing the
      expression of FoxO3a in the nucleus. The efficacy of aged hMSC transplantation
      therapy for ischaemic heart diseases can be improved by SIRT3 overexpression.

PMID- 30091832
TI  - Snapshot of an early Paleoproterozoic ecosystem: Two diverse microfossil
      communities from the Turee Creek Group, Western Australia.
AB  - Eighteen microfossil morphotypes from two distinct facies of black chert from a
      deep-water setting of the c. 2.4 Ga Turee Creek Group, Western Australia, are
      reported here. A primarily in situ, deep-water benthic community preserved in
      nodular black chert occurs as a tangled network of a variety of long filamentous
      microfossils, unicells of one size distribution and fine filamentous rosettes,
      together with relatively large spherical aggregates of cells interpreted as in
      fallen, likely planktonic, forms. Bedded black cherts, in contrast, preserve
      microfossils primarily within, but also between, rounded clasts of organic
      material that are coated by thin, convoluted carbonaceous films interpreted as
      preserved extracellular polymeric substance (EPS). Microfossils preserved within
      the clasts include a wide range of unicells, both much smaller and larger than
      those in the nodular black chert, along with relatively short, often degraded
      filaments, four types of star-shaped rosettes and umbrella-like rosettes. Large,
      complexly branching filamentous microfossils are found between the clasts. The
      grainstone clasts in the bedded black chert are interpreted as transported from
      shallower water, and the contained microfossils thus likely represent a
      phototrophic community. Combined, the two black chert facies provide a snapshot
      of a microbial ecosystem spanning shallow to deeper-water environments, and an
      insight into the diversity of life present during the rise in atmospheric oxygen.
      The preserved microfossils include two new, distinct morphologies previously
      unknown from the geological record, as well as a number of microfossils from the
      bedded black chert that are morphologically similar to-but 400-500 Ma older than
      type specimens from the c. 1.88 Ga Gunflint Iron Formation. Thus, the Turee Creek
      Group microfossil assemblage creates a substantial reference point in the sparse
      fossil record of the earliest Paleoproterozoic and demonstrates that microbial
      life diversified quite rapidly after the end of the Archean.

PMID- 30091833
TI  - Nicotine induces endothelial dysfunction and promotes atherosclerosis via GTPCH1.
AB  - Smoking is a major preventable risk factor for atherosclerosis. However, the
      causative link between cigarette smoke and atherosclerosis remains to be
      established. The objective of this study is to characterize the role of GTP
      cyclohydrolase 1 (GTPCH1), the rate-limiting enzyme for de novo
      tetrahydrobiopterin (BH4) synthesis, in the smoking-accelerated atherosclerosis
      and the mechanism involved. In vitro, human umbilical vein endothelial cells were
      treated with nicotine, a major component of cigarette smoke, which reduced the
      mRNA and protein levels of GTPCH1 and led to endothelial dysfunction. GTPCH1
      overexpression or sepiapterin could attenuate nicotine-reduced nitric oxide and 
      increased reactive oxygen species levels. Mechanistically, human antigen R (HuR)
      bound with the adenylateuridylate-rich elements of the GTPCH1 3' untranslated
      region and increased its stability; nicotine inhibited HuR translocation from the
      nucleus to cytosol, which downregulated GTPCH1. In vivo, nicotine induced
      endothelial dysfunction and promoted atherosclerosis in ApoE-/- mice, which were
      attenuated by GTPCH1 overexpression or BH4 supplement. Our findings may provide a
      novel and promising approach to atherosclerosis treatment.

PMID- 30091836
TI  - Exploring reasons for vaccine-hesitancy among higher-SES parents in Perth,
      Western Australia.
AB  - ISSUES ADDRESSED: The increasing prevalence among higher-socioeconomic (higher
      SES) parents in Perth, Western Australia (WA), to be vaccine-hesitant (VH) is
      placing herd immunity at risk. METHODS: Eighteen one-on-one interviews were
      conducted; (n = 11) parents who earned >$125 000 pa and expressed ever having
      concerns surrounding vaccination; (n = 7) health care professionals (HCPs), who
      provided clinical services. Using grounded theory methodology, data were analysed
      by constant coding and comparison until themes emerged and an explanatory model
      was developed. RESULTS: Four main areas leading to vaccine-hesitancy emerged from
      the data: We are Educated; We Control our Health; Safe from Disease, At Risk from
      Vaccines; and What We Want. Parents believed themselves capable of making good
      vaccination decisions based on their higher education levels and self-sourced
      vaccination information, yet frequently sought reassurance. Healthism concepts
      were adopted and parents believed lifestyle factors could control for vaccine
      preventable diseases (VPD). Risk perception of disease was low and influenced by
      the remote geographic location of Perth, whilst perceived negative consequences
      of vaccination were high. A reduced concept of the social responsibility for
      vaccination and understanding of herd immunity emerged. Parents called for
      vaccine contents to be listed and requested more information on why vaccination
      was necessary. CONCLUSION: Four areas of VH emerged and reflected parents' belief
      that higher educational and socioeconomic status, previous successes in life and
      where they live would result in positive health outcomes and reduce the risk of
      contracting VPDs. SO WHAT?: This study provides new research into the perceptions
      among higher-SES VH parents who live in Perth, WA. It provides a model that fills
      a significant gap in information that could be used effectively for future health
      promotion interventions.

PMID- 30091834
TI  - rSjP40 suppresses hepatic stellate cell activation by promoting microRNA-155
      expression and inhibiting STAT5 and FOXO3a expression.
AB  - Activation of hepatic stellate cells (HSCs) is the central event of the evolution
      of hepatic fibrosis. Schistosomiasis is one of the pathogenic factors which could
      induce hepatic fibrosis. Previous studies have shown that recombinant Schistosoma
      japonicum egg antigen P40 (rSjP40) can inhibit the activation and proliferation
      of HSCs. MicroRNA-155 is one of the multifunctional noncoding RNA, which is
      involved in a series of important biological processes including cell
      development, proliferation, differentiation and apoptosis. Here, we try to
      observe the role of microRNA-155 in rSjP40-inhibited HSC activation and explore
      its potential mechanisms. We found that microRNA-155 was raised in rSjP40-treated
      HSCs, and further studies have shown that rSjP40 enhanced microRNA-155 expression
      by inhibiting STAT5 transcription. Up-regulated microRNA-155 can down-regulate
      the expression of FOXO3a and then participate in rSjP40-inhibited expression of
      alpha-smooth muscle actin (alpha-SMA) and collagen I. Furthermore, we observed
      microRNA-155 inhibitor could partially restore the down-regulation of FOXO3a,
      alpha-SMA and collagen I expression in LX-2 cells induced by rSjP40. Therefore,
      our research provides further insight into the mechanism by which rSjP40 could
      inhibit HSC activation via miR-155.

PMID- 30091835
TI  - 25-Hydroxycholesterol protects against acute lung injury via targeting MD-2.
AB  - Acute lung injury (ALI) is mainly caused by uncontrolled inflammatory response,
      and it remains without effective therapeutic options. 25-hydroxycholesterol
      (25HC) has been reported to be a potent regulator of inflammation. The aim of
      this study was to investigate the effects of 25HC on lipopolysaccharide (LPS)
      induced ALI. C57BL/6 mice were pretreated with 25HC intraperitoneally before
      intratracheal exposure to LPS. Our results showed that 25HC pretreatment improved
      survival rate, attenuated the pathological changes of the lung and decreased the
      release of inflammatory cytokines in mice. Consistently, 25HC reduced expression
      of Toll-like receptor (TLR4)-mediated inflammatory cytokines in vitro. These
      effects of 25HC were obtained by preventing LPS binding to TLR4 via interaction
      with myeloid differentiation protein 2 (MD-2). Crystal structure analysis
      suggested that 25HC could bind MD-2 with high affinity into its hydrophobic
      pocket. Furthermore, LPS-induced activation of Akt/NF-kappaB pathway was
      partially down-regulated by 25HC pretreatment. In summary, this study
      demonstrates that 25HC could inhibit the overwhelming inflammatory response
      through MD-2 interaction, which suppresses Akt/NF-kappaB signalling pathway.
      These findings suggest 25HC may be a promising candidate for ALI prevention.

PMID- 30091837
TI  - Visualizing Nanoscale Coronal Segregation in Rod-Like Micelles Formed by Co
      Assembly of Binary Block Copolymer Blends.
AB  - Mixed micelles formed by co-assembly of pairs of block copolymers (BCPs) can
      develop novel morphologies and generate useful properties not accessible from
      homomicelles. For micelles consisting of two different polymers in the corona,
      identifying the location of the corona chains is a critical part of morphology
      characterization. Coronal segregation in mixed micelle is often characterized by
      transmission electron microscopy in combination with selective staining of
      individual polymers. In this study, Karstedt's catalyst is used for selective
      Pt(0)-olefin coordination staining of polyisoprene (PI) and
      poly(methylvinylsiloxane) (PMVS) corona chains in the presence of
      poly(dimethylsiloxane) (PDMS) corona chains in cylindrical mixed micelles with a
      crystalline poly(ferrocenyldimethylsilane) (PFS) core. Previous experiments using
      OsO4 as a stain did not enable visualization of nanoscale coronal segregation in
      mixed micelles obtained from co-assembly of PFS-b-PI and PFS-b-PDMS, as well as
      PFS-b-PMVS and PFS-b-PDMS.

PMID- 30091838
TI  - European perspectives on big data applied to health: The case of biobanks and
      human databases.
AB  - INTRODUCTION: The paradigm shift to a knowledge-based economy has incremented the
      use of personal information applied to health-related activities, such as
      biomedical research, innovation, and commercial initiatives. The convergence of
      science, technology, communication and data technologies has given rise to the
      application of big data to health; for example through eHealth, human databases
      and biobanks. METHODS: In light of these changes, we enquire about the value of
      personal data and its appropriate use. In order to illustrate the complex ground
      on which big data applied to health develops, we analyse the current situation of
      the European Union and two cases: the Catalan VISC+/PADRIS and the UK Biobank, as
      perspectives. DISCUSSION AND CONCLUSIONS: Personal health-related data in the
      context of the European Union is being increasingly used for big data projects
      under diverse schemes. There, public and private sectors participate
      distinctively or jointly, pursuing very different goals which may conflict with
      individual rights, notably privacy. Given that, this paper advocates for stopping
      the unjustified accumulation and commercialisation of personal data, protecting
      the interests of citizens and building appropriate frameworks to govern big data
      projects for health. A core tool for achieving such goals is to develop consent
      mechanisms which allow truly informed but adaptable consent, conjugated with the
      engagement of donors, participants and society.

PMID- 30091839
TI  - Cognitive disorders in normal pressure hydrocephalus with initial parkinsonism in
      comparison with de novo Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: The clinical differentiation between parkinsonism in
      idiopathic normal pressure hydrocephalus (iNPH) and Parkinson's disease (PD)
      remains challenging in the initial phase. Whether an early cognitive profiling
      might support the differential diagnosis of early iNPH and PD was addressed.
      METHODS: Neuropsychological tests of 40 iNPH subjects with early symptoms
      resembling parkinsonism were retrospectively evaluated together with 47 de novoPD
      patients (dnPD). Only neuropsychological tests performed within 1 year from the
      first motor symptom were included. The cognitive spectrum of iNPH and dnPD was
      also compared with a sample of 70 normal controls. RESULTS: A clear difference in
      the cognitive profile of iNPH, dnPD patients and normal controls was shown. 65%
      of iNPH subjects showed a diffuse cognitive impairment, including memory,
      visuospatial abilities, fronto-executive functioning and attention, whereas only
      25.5% of the dnPD patients presented an executive dysfunction. 35% of iNPH and
      74.5% of PD patients performed within the normal range (P < 0.05). CONCLUSION:
      Subjects with iNPH showed an early and diffuse alteration of cognition with
      respect to dnPD patients. Performing a prompt and accurate neuropsychological
      evaluation might support the differential diagnosis of these two conditions of
      parkinsonism.

PMID- 30091840
TI  - Can you hear me now? Patient preferences for evaluating kidney transplant
      centers.

PMID- 30091841
TI  - Kidney transplant offers to deceased candidates.

PMID- 30091842
TI  - Burkholderia multivorans septicemia in a pediatric liver transplant patient.
AB  - "Cepacia syndrome", caused by Burkholderia cepacia complex and often associated
      with cystic fibrosis, carries a high mortality rate. It is rare for Burkholderia
      multivorans, a species within the B. cepacia complex, to cause cepacia syndrome
      even among patients with cystic fibrosis. This is the first reported fatal case
      of cepacia syndrome caused by B. multivorans occurring in a pediatric liver
      transplant recipient who does not have cystic fibrosis. We describe the unique
      characteristics of this pathogen among the non-cystic fibrosis population and the
      importance of early recognition and treatment.

PMID- 30091843
TI  - Insights about the Absence of Rb Cation from the 3D Perovskite Lattice: Effect on
      the Structural, Morphological, and Photophysical Properties and Photovoltaic
      Performance.
AB  - Efficiencies >20% are obtained from the perovskite solar cells (PSCs) employing
      Cs+ and Rb+ based perovskite compositions; therefore, it is important to
      understand the effect of these inorganic cations specifically Rb+ on the
      properties of perovskite structures. Here the influence of Cs+ and Rb+ is
      elucidated on the structural, morphological, and photophysical properties of
      perovskite structures and the photovoltaic performances of resulting PSCs.
      Structural, photoluminescence (PL), and external quantum efficiency studies
      establish the incorporation of Cs+ (x < 10%) but amply rule out the possibility
      of Rb-incorporation into the MAPbI3 (MA = CH3 NH3+ ) lattice. Moreover,
      morphological studies and time-resolved PL show that both Cs+ and Rb+
      detrimentally affect the surface coverage of MAPbI3 layers and charge-carrier
      dynamics, respectively, by influencing nucleation density and by inducing
      nonradiative recombination. In addition, differential scanning calorimetry shows
      that the transition from orthorhombic to tetragonal phase occurring around 160 K
      requires more thermal energy for the Cs-containing MAPbI3 systems compared to the
      pristine MAPbI3 . Investigation including mixed halide (I/Br) and mixed cation A
      cation based compositions further confirms the absence of Rb+ from the 3D
      perovskite lattice. The fundamental insights gained through this work will be of
      great significance to further understand highly promising perovskite
      compositions.

PMID- 30091844
TI  - A Smart Flexible Solid State Photovoltaic Device with Interfacial Cooling
      Recovery Feature through Thermoreversible Polymer Gel Electrolyte.
AB  - Quasi-solid-state dye-sensitized solar cells (DSSCs) fabricated with lightweight
      flexible substrates have a great potential in wearable electronic devices for in
      situ powering. However, the poor lifespan of these DSSCs limits their practical
      application. Strong mechanical stresses involved in practical applications cause
      breakage of the electrode/electrolyte interface in the DSSCs greatly affecting
      their performance and lifetime. Here, a mechanically robust, low-cost, long
      lasting, and environment-friendly quasi-solid-state DSSC using a smart
      thermoreversible water-based polymer gel electrolyte with self-healing
      characteristics at a low temperature (below 0  degrees C) is demonstrated. When
      the performance of the flexible DSSC is hindered by strong mechanical stresses
      (i.e., from multiple bending/twisting/shrinking actions), a simple cooling
      treatment can regenerate the electrode/electrolyte interface and recover the
      performance close to the initial level. A performance recovery as high as 94% is
      proven possible even after 300 cycles of 90 degrees  bending. To the best of our
      knowledge, this is the first aqueous DSSC device with self-healing behavior,
      using a smart thermoreversible polymer gel electrolyte, which provides a new
      perspective in flexible wearable solid-state photovoltaic devices.

PMID- 30091845
TI  - A Microfluidic Strategy for Controllable Generation of Water-in-Water Droplets as
      Biocompatible Microcarriers.
AB  - Droplet microfluidics has been widely applied in functional microparticles
      fabricating, tissue engineering, and drug screening due to its high throughput
      and great controllability. However, most of the current droplet microfluidics are
      dependent on water-in-oil (W/O) systems, which involve organic reagents, thus
      limiting their broader biological applications. In this work, a new microfluidic
      strategy is described for controllable and high-throughput generation of
      monodispersed water-in-water (W/W) droplets. Solutions of polyethylene glycol and
      dextran are used as continuous and dispersed phases, respectively, without any
      organic reagents or surfactants. The size of W/W droplets can be precisely
      adjusted by changing the flow rate of dispersed and continuous phases and the
      valve switch cycle. In addition, uniform cell-laden microgels are fabricated by
      introducing the alginate component and rat pancreatic islet (beta-TC6) cell
      suspension to the dispersed phase. The encapsulated islet cells retain high
      viability and the function of insulin secretion after cultivation for 7 days. The
      high-throughput droplet microfluidic system with high biocompatibility is stable,
      controllable, and flexible, which can boost various chemical and biological
      applications, such as bio-oriented microparticles synthesizing, microcarriers
      fabricating, tissue engineering, etc.

PMID- 30091846
TI  - Combined immuno-purification and detection of recombinant erythropoietins and
      activin receptor type II-Fc fusion proteins by isoelectric focusing for
      application in doping control.
AB  - Iso-electric focusing (IEF) was the first method established to discriminate
      endogenous and recombinant erythropoietins (rEPOs). It is still approved by the
      World Anti-Doping Agency (WADA) as an initial testing procedure to detect
      erythropoiesis stimulating agents (ESAs) in doping control samples. However EPO
      Fc, one of the prohibited rEPOs designated by WADA, is not detectable with the
      actual IEF conditions. Other newly developed ESAs - luspatercept and sotatercept,
      both activin receptor type II-Fc fusion proteins (ActRII-Fc) - are also now
      prohibited and could be used in combination with rEPOs. Methods of identification
      of ActRII-Fc in blood by SAR/SDS-PAGE have been described, but not by IEF. Here
      we detail improvements in blood sample preparation and IEF analysis: A combined
      immuno-purification of EPOs and ActRII-Fc proteins in a single procedure, an
      appropriate isoforms separation for all proteins using new pre-loading and gel
      conditions, and a single detection of all rEPOs and ActRII-Fc proteins after
      successive incubation with anti-EPO and anti-ActRII antibodies. With these
      changes, distinctive profiles for all the ESAs were obtained by IEF. Therefore,
      IEF could be used as a screening method to detect a wide spectrum of prohibited
      ESAs in blood samples prior to specific confirmation for the identified rEPO or
      ActRII-Fc.

PMID- 30091847
TI  - Tug-of-War in a Dynamic Helical Peptide: Solvent-Induced Helix-Helix Transition
      of a Lactam-Bridged Peptide Composed of Point- and Axial Chiralities Remote from
      Each Other.
AB  - The dynamic axial chirality of oligopeptide-bound 2,2'-bipyridine (bpy) residues
      can be remote-controlled and diastereoselectively locked. A right-handed (P)-310 
      helix is first induced in the dynamic helical oligopeptide by an l-valine (l-Val)
      far from the bpy moiety and the induced axial bpy chirality is
      diastereoselectively dioxidized. The resulting l-Val-containing linear
      oligopeptides at the 3,3'-positions retain their (P)-310 -helices independent of
      the axial chirality (aR or aS) of the N-terminal N,N'-dioxide-bpy unit, while a
      lactam-bridged dynamic helical oligopeptide exhibits a unique solvent-induced
      helix-helix transition as a result of competitive helix-inducing biases between
      the l-Val and (aR) or (aS)-N,N'-dioxide-bpy residues remote from each other along
      the entire oligopeptide chain in a tug-of-war like manner.

PMID- 30091848
TI  - One-Dimensional Electrophoresis Using Nondenaturing Conditions.
AB  - Electrophoresis is used to separate complex mixtures of proteins (e.g., from
      cells, subcellular fractions, column fractions, or immunoprecipitates), to
      investigate subunit composition, track post-translational modifications, and
      verify identity and homogeneity of protein samples. It can also serve to purify
      proteins for use in further applications. In polyacrylamide gel electrophoresis,
      proteins migrate in response to an electrical field through pores in a
      polyacrylamide gel matrix; pore size decreases with increasing acrylamide
      concentration. Nondenaturing or "native" electrophoresis-i.e., electrophoresis in
      the absence of denaturants such as detergents and urea-is an often-overlooked
      technique for determining the native size, subunit structure, and optimal
      separation of a protein. Because mobility depends on the size, shape, and
      intrinsic charge of the protein, nondenaturing electrophoresis provides a set of
      separation parameters distinctly different from mainly size-dependent denaturing
      sodium dodecyl sulfate-polyacrylamide gel electrophoresis and charge-dependent
      isoelectric focusing. Two protocols are presented below. Continuous PAGE is
      highly flexible, permitting cationic and anionic electrophoresis over a full
      range of pH. The discontinuous procedure is limited to proteins negatively
      charged at neutral pH but provides high resolution for accurate size calibration.

PMID- 30091849
TI  - Evaluation of resource burden for bladder adaptive strategies: A timing study.
AB  - INTRODUCTION: Interfraction bladder motion is substantial and therefore many
      different adaptive radiotherapy approaches have been developed to accommodate
      that motion. Previous studies comparing the efficacy of those adaptive strategies
      have demonstrated that reoptimization (ReOpt) was dosimetrically superior when
      compared to Plan of the Day (POD) and Patient-specific PTV (PS-PTV). However, the
      feasibility of clinical implementation is dependent upon assessment of the
      resource burden. This study assessed and compared the resource burden of three
      adaptive strategies. METHODS: Using the planning CT and all daily CBCTs of 10
      bladder patients, the following adaptive strategies were simulated offline to
      deliver 46 Gy in 23 fractions: POD, PS-PTV and ReOpt. Additional activities
      required to execute these strategies compared to a nonadaptive approach were
      identified and categorized. Time consumed for the execution of each strategy was
      measured for a single, experienced observer. RESULTS: The time (minutes) consumed
      to execute the additional activities for PS-PTV, POD and ReOpt was 14.4, 49.1 and
      248.5, respectively. In addition to a significantly shorter time spent, all
      activities associated with PS-PTV were categorized as those that could be
      performed without the presence of the patient or a treatment room. On the other
      hand, ReOpt was the most time intensive and all activities were categorized as
      those that could lead to increasing patient's time in the treatment room and
      decreasing capacity. CONCLUSIONS: Although ReOpt was preferred with respect to
      improving dosimetry, the heavy resource burden it incurred could be a deterrent
      for clinical implementation. PS-PTV was the least resource-intensive strategy.

PMID- 30091850
TI  - High tissue eosinophilia as a marker to predict recurrence for eosinophilic
      chronic rhinosinusitis: a systematic review and meta-analysis.
AB  - BACKGROUND: Patients with eosinophilic chronic rhinosinusitis (ECRS) have been
      shown to have greater disease severity and poorer treatment outcomes after sinus
      surgery. Although the inflammatory pattern of ECRS is essential to diagnosing
      this subtype, there is currently no consensus for diagnosis. Our aim in this
      study was to determine whether high tissue eosinophilia (HTE), measured as
      eosinophils per high-power field (eos/HPF), could be used to define ECRS based on
      likelihood of recurrence. METHODS: Embase, Medline, and PubMed databases were
      searched for studies that reported HTE and recurrence in ECRS patients after
      surgical treatment. We used a random-effects bivariate meta-analysis to calculate
      summary sensitivity, specificity, and diagnostic odds ratios (DORs) for detecting
      ECRS at different HTE cut-off scores using risk of recurrence as the primary
      outcome. RESULTS: We identified 11 articles (n = 3183) that reported HTE
      associated with recurrence. A cut-off value of >55 eos/HPF showed the highest
      sensitivity (0.87; 95% confidence interval [CI], 0.82-0.91), specificity (0.97;
      95% CI, 0.93-0.99), and DOR (232.7; 95% CI, 91.0-595.1). Meta-regression analysis
      performed showed that the Quality Assessment of Diagnostic Accuracy Studies score
      (p = 0.1287), geographic location (p = 0.3745), follow-up time (p = 0.2879), and
      study design (p = 0.1865) did not affect the test accuracy. CONCLUSION: Our
      findings suggest that using eos/HPF has good diagnostic accuracy and may be a
      useful tool for identifying ECRS patients. Based on the results of our meta
      analysis, we recommend a cut-off value of >55 eos/HPF for predicting the
      likelihood of recurrence of ECRS.

PMID- 30091851
TI  - Isolation of Antibodies to Heparan Sulfate on Glypicans by Phage Display.
AB  - Heparan sulfate (HS) plays an important role in development and disease. It
      interacts with many growth factors, chemokines, and other ligands known to be
      important for cell growth, motility, and differentiation. However, isolating an
      antibody to HS in mice, rabbits, or humans is difficult due to the poor
      immunogenicity of HS. Phage display is a major antibody engineering technology
      that allows the selection of antibodies for poorly immunogenic or highly
      conserved antigens. This protocol contains detailed procedures for HS antigen
      preparation and isolation of a phage displayed human single-chain Fv (HS20) that
      binds HS on glypican-3 (GPC3), and analysis of the selected phage antibody. It is
      conceivable that the procedures described in this protocol may be applicable to
      the isolation of antibodies for a variety of HS molecules. (c) 2018 by John Wiley
      & Sons, Inc.

PMID- 30091852
TI  - Phase 1 Single- and Multiple-Ascending-Dose Randomized Studies of the Safety,
      Pharmacokinetics, and Pharmacodynamics of AG-348, a First-in-Class Allosteric
      Activator of Pyruvate Kinase R, in Healthy Volunteers.
AB  - Pyruvate kinase deficiency is a chronic hemolytic anemia caused by mutations in
      PK-R, a key glycolytic enzyme in erythrocytes. These 2 phase 1 randomized,
      placebo-controlled, double-blind healthy-volunteer studies assessed the safety,
      tolerability, and pharmacokinetics/pharmacodynamics of AG-348, a first-in-class
      allosteric PK-R activator. Twelve sequential cohorts were randomized 2:6 to
      receive oral placebo or AG-348, respectively, as a single dose (30-2500 mg) in
      the single-ascending-dose (SAD) study (ClinicalTrials.gov: NCT02108106) or 15-700
      mg every 12 hours or 120 mg every 24 hours, for 14 days in the multiple-ascending
      dose (MAD) study (ClinicalTrials.gov: NCT02149966). All 48 subjects completed the
      fasted SAD part; 44 of 48 completed the MAD (2 discontinued because of adverse
      events [AEs], 2 withdrew consent). The most common treatment-related AEs in AG
      348-treated subjects were headache (16.7% [SAD] and 13.9% [MAD]) and nausea
      (13.9%, both studies). AE frequency increased at AG-348 doses >= 700 mg (SAD) and
      at 700 mg every 12 hours (MAD); 1 grade >= 3 AE occurred in the latter cohort.
      Pharmacokinetics were favorable with low variability. Dose-dependent changes in
      blood glycolytic intermediates consistent with glycolytic pathway activation were
      observed at all MAD doses, supporting future trials investigating the potential
      of AG-348 for treating PK deficiency or other anemias.

PMID- 30091853
TI  - Oxytocin analysis from human serum, urine, and saliva by orbitrap liquid
      chromatography-mass spectrometry.
AB  - Oxytocin (OT) is a neurohormone that has gained interest recently due to its
      emerging role in cognition and social/emotional behaviors, including possibly
      depression and autism. OT is commonly measured using enzyme- or radio-based
      immunoassays (RIA, ELISA), which lack specificity or are complicated to perform
      and involve hazardous radioactive material. We have developed a high resolution
      accurate-mass (HRAM) liquid chromatography-mass spectrometry (LC-MS) method that
      separates interferences and selectively and accurately quantitates native OT from
      human serum, urine, and saliva after solid phase extraction. The doubly
      protonated OT ion m/z 562.25503 was selected for quantitation due its high signal
      intensity. With our method lower limit of detection (LLOD) of 5-25 pg/mL, we
      measured native OT in serum from pregnant women (16-24 pg/mL) and rats (350
      pg/mL), and in serum, urine, and saliva from a healthy male after intranasal (IN)
      OT application of 100 IU and 20 IU and from a healthy post-menopausal female
      after IN OT application of 100 IU. Peak levels were detected in serum, urine, and
      saliva 15-30 minutes after each dose then decreased to below detection limits 1-2
      hours thereafter. We were unable to detect native OT in serum from non
      pregnant/non-lactating/non-medicated women due to levels known to occur below 5
      pg/mL. The fast elimination of OT we found is in excellent agreement with the
      pharmacokinetics of OT in other studies. The effects on the central nervous
      system occurring after IN OT administration remains to be determined.

PMID- 30091854
TI  - Highly multiplexed proteomic analysis reveals significant tissue and exosomal
      coagulation pathway derangement in chronic rhinosinusitis with nasal polyps.
AB  - BACKGROUND: The coagulation pathway has been previously implicated in the
      etiopathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) through
      analysis of individual proteins within the cascade. The purpose of this study was
      to: (1) apply a large-scale proteomic approach to confirm these previous
      findings; and (2) correlate the protein aberrations between tissue and exosomes
      to establish exosomal proteomics as a method to probe the pathophysiology of
      CRSwNP. METHODS: This investigation was an internal review board-approved study
      in which matched tissue and mucus exosomal proteomes were compared between
      control and CRSwNP (n = 10/group) using an aptamer-based proteomic array and
      confirmed using whole transcriptome sequencing. Protein expression and the
      correlation between samples were calculated using Student's t-test and Benjamini
      Hochberg procedures followed by the application of Ingenuity Pathway and
      MetaCoreTM bioinformatics analyses. RESULTS: Among all protein pathways, the
      coagulation cascade was the most significantly associated with CRSwNP (p = 2.85e
      8). Among the 13 significantly altered coagulation-related tissue proteins,
      fibronectin and fibrinogen gamma chains were the most overexpressed in CRSwNP
      relative to control (fold change [FC], 2.59; p = 0.006; and FC, 2.38; p < 0.001,
      respectively), whereas von Willebrand factor was the most underexpressed (FC, 
      3.06; p < 0.001). The exosomal fibrinolysis and coagulation pathway proteomes
      exhibited strong inverse and significant correlations with the tissue findings (r
      = -0.86; p = 0.013; and r = -0.79; p = 0.007, respectively). CONCLUSION: Our
      proteomic analysis confirmed that the coagulation pathway is highly significantly
      deranged within nasal polyp tissue. The correlation between tissue- and mucus
      derived exosomal fibrinolysis and coagulation protein alterations were strong,
      inverse, and highly significant. This lends further support to the emerging
      concept of exosomal proteomic analysis as a method to study chronic sinonasal
      inflammation.

PMID- 30091855
TI  - Three-Component Mixture Model-Based Adverse Drug Event Signal Detection for the
      Adverse Event Reporting System.
AB  - The US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS)
      is an important source for detecting adverse drug event (ADE) signals. In this
      article, we propose a three-component mixture model (3CMM) for FAERS signal
      detection. In 3CMM, a drug-ADE pair is assumed to have either a zero relative
      risk (RR), or a background RR (mean RR = 1), or an increased RR (mean RR >1). By
      clearly defining the second component (mean RR = 1) as the null distribution,
      3CMM estimates local false discovery rates (FDRs) for ADE signals under the
      empirical Bayes framework. Compared with existing approaches, the local FDR's top
      signals have noninferior or better sensitivities to detect true signals in both
      FAERS analysis and simulation studies. Additionally, we identify that the top
      signals of different approaches have different patterns, and they are
      complementary to each other.

PMID- 30091856
TI  - Renal Tubular- and Vascular Basement Membranes and their Mimicry in Engineering
      Vascularized Kidney Tubules.
AB  - The high prevalence of chronic kidney disease leads to an increased need for
      renal replacement therapies. While there are simply not enough donor organs
      available for transplantation, there is a need to seek other therapeutic avenues
      as current dialysis modalities are insufficient. The field of regenerative
      medicine and whole organ engineering is emerging, and researchers are looking for
      innovative ways to create (part of) a functional new organ. To biofabricate a
      kidney or its functional units, it is necessary to understand and learn from
      physiology to be able to mimic the specific tissue properties. Herein is provided
      an overview of the knowledge on tubular and vascular basement membranes'
      biochemical components and biophysical properties, and the major differences
      between the two basement membranes are highlighted. Furthermore, an overview of
      current trends in membrane technology for developing renal replacement therapies
      and to stimulate kidney regeneration is provided.

PMID- 30091857
TI  - Defining the optimal duration for normothermic regional perfusion in the kidney
      donor: A porcine preclinical study.
AB  - Kidneys from donation after circulatory death (DCD) are highly sensitive to
      ischemia-reperfusion injury and thus require careful reconditioning, such as
      normothermic regional perfusion (NRP). However, the optimal NRP protocol remains
      to be characterized. NRP was modeled in a DCD porcine model (30 minutes of
      cardiac arrest) for 2, 4, or 6 hours compared to a control group (No-NRP);
      kidneys were machine-preserved and allotransplanted. NRP appeared to permit
      recovery from warm ischemia, possibly due to an increased expression of HIF1alpha
      dependent survival pathway. At 2 hours, blood levels of ischemic injury
      biomarkers increased: creatinine, lactate/pyruvate ratio, LDH, AST, NGAL, KIM-1,
      CD40 ligand, and soluble-tissue-factor. All these markers then decreased with
      time; however, AST, NGAL, and KIM-1 increased again at 6 hours. Hemoglobin and
      platelets decreased at 6 hours, after which the procedure became difficult to
      maintain. Regarding inflammation, active tissue-factor, cleaved PAR-2 and MCP-1
      increased by 4-6 hours, but not TNF-alpha and iNOS. Compared to No-NRP, NRP
      kidneys showed lower resistance during hypothermic machine perfusion (HMP),
      likely associated with pe-NRP eNOS activation. Kidneys transplanted after 4 and 6
      hours of NRP showed better function and outcome, compared to No-NRP. In
      conclusion, our results confirm the mechanistic benefits of NRP and highlight 4
      hours as its optimal duration, after which injury markers appear.

PMID- 30091858
TI  - Semimechanistic Population Pharmacokinetic Model to Predict the Drug-Drug
      Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers.
AB  - Low-dose oral S-ketamine is increasingly used in chronic pain therapy, but
      extensive cytochrome P450 (CYP) mediated metabolism makes it prone to
      pharmacokinetic drug-drug interactions (DDIs). In our study, concentration-time
      data from five studies were used to develop a semimechanistic model that
      describes the ticlopidine-mediated inhibition of S-ketamine biotransformation. A
      mechanistic model was implemented to account for reversible and time-dependent
      hepatic CYP2B6 inactivation by ticlopidine, which causes elevated S-ketamine
      exposure in vivo. A pharmacokinetic model was developed with gut wall and hepatic
      clearances for S-ketamine, its primary metabolite norketamine, and ticlopidine.
      Nonlinear mixed effects modeling approach was used (NONMEM version 7.3.0), and
      the final model was evaluated with visual predictive checks and the sampling
      importance-resampling procedure. Our final model produces biologically plausible
      output and demonstrates that ticlopidine is a strong inhibitor of CYP2B6 mediated
      S-ketamine metabolism. Simulations from our model may be used to evaluate chronic
      pain therapy with S-ketamine.

PMID- 30091859
TI  - Nanoscale Discrimination between Toxic and Nontoxic Protein Misfolded Oligomers
      with Tip-Enhanced Raman Spectroscopy.
AB  - Highly toxic protein misfolded oligomers associated with neurological disorders
      such as Alzheimer's and Parkinson's diseases are nowadays considered primarily
      responsible for promoting synaptic failure and neuronal death. Unraveling the
      relationship between structure and neurotoxicity of protein oligomers appears
      pivotal in understanding the causes of the pathological process, as well as in
      designing novel diagnostic and therapeutic strategies tuned toward the earliest
      and presymptomatic stages of the disease. Here, it is benefited from tip-enhanced
      Raman spectroscopy (TERS) as a surface-sensitive tool with spatial resolution on
      the nanoscale, to inspect the spatial organization and surface character of
      individual protein oligomers from two samples formed by the same polypeptide
      sequence and different toxicity levels. TERS provides direct assignment of
      specific amino acid residues that are exposed to a large extent on the surface of
      toxic species and buried in nontoxic oligomers. These residues, thanks to their
      outward disposition, might represent structural factors driving the pathogenic
      behavior exhibited by protein misfolded oligomers, including affecting cell
      membrane integrity and specific signaling pathways in neurodegenerative
      conditions.

PMID- 30091860
TI  - On PrEP and the Daily Mail.

PMID- 30091861
TI  - Marketplaces, Markets, and Market Design.
AB  - Marketplaces are often small parts of large markets, and both markets and
      marketplaces come in many varieties. Market design seeks to understand what
      marketplaces must accomplish to enable different kinds of markets. Marketplaces
      can have varying degrees of success, and there can be marketplace failures. I'll
      discuss labor markets like the market for new economists, and also markets for
      new lawyers and doctors that have suffered from the unraveling of appointment
      dates to well before employment begins. Markets work best if they enjoy social
      support, but some markets are repugnant in the sense that some people think they
      should be banned, even though others want to participate in them. Laws banning
      such markets often contribute to the design of illegal black markets, and this
      raises new issues for market designers. I'll briefly discuss markets and black
      markets for narcotics, marijuana, sex, and surrogacy, and the design of markets
      for kidney transplants, in the face of widespread laws against (and broader
      repugnance for) compensating organ donors. I conclude with open questions and
      engineering challenges.

PMID- 30091862
TI  - Do Larger Health Insurance Subsidies Benefit Patients or Producers? Evidence from
      Medicare Advantage.
AB  - A central question in the debate over privatized Medicare is whether increased
      government payments to private Medicare Advantage (MA) plans generate lower
      premiums for consumers or higher profits for producers. Using difference-in
      differences variation brought about by a sharp legislative change, we find that
      MA insurers pass through 45 percent of increased payments in lower premiums and
      an additional 9 percent in more generous benefits. We show that advantageous
      selection into MA cannot explain this incomplete pass-through. Instead, our
      evidence suggests that market power is important, with premium pass-through rates
      of 13 percent in the least competitive markets and 74 percent in the most
      competitive.

PMID- 30091863
TI  - Health Care Sharing Ministries: What Are the Risks to Consumers and Insurance
      Markets?
AB  - Issue: Health care sharing ministries (HCSMs) are a form of health coverage in
      which members--who typically share a religious belief--make monthly payments to
      cover expenses of other members. HCSMs do not have to comply with the consumer
      protections of the Affordable Care Act and may provide value for some
      individuals, but pose risks for others. Although HCSMs are not insurance and do
      not guarantee payment of claims, their features closely mimic traditional
      insurance products, possibly confusing consumers. Because they are largely
      unregulated and provide limited benefits, HCSMs may be disproportionately
      attractive to healthy individuals, causing the broader insurance market to become
      smaller, sicker, and more expensive. Goal: To understand state regulator
      perspectives on regulation of HCSMs and the impact of these arrangements on
      consumers and markets. Methods: Analysis of state laws governing HCSMs in all
      states; interviews with officials in 13 states; and review of the membership
      requirements and benefits of five HCSMs. Findings and Conclusions: State
      regulators voiced concerns regarding the potential risks of HCSMs to consumers
      and their individual markets. However, in the absence of reliable data describing
      HCSM enrollment, regulators cannot adequately assess harm. Though limited
      resources and political constraints have made oversight difficult, all states,
      regardless of their regulatory approach to HCSMs, should obtain data to better
      understand the role of HCSMs in their markets.

PMID- 30091864
TI  - I survived my heart attack but the NHS's arteries are in trouble.
AB  - A personal emergency brought home the huge gap between staff's compassion and the
      resources available.

PMID- 30091865
TI  - Trade deals with Trump could give the NHS a heart attack.
AB  - Labour must come to terms with the gains of the Blair years, while the Tories
      must be wary of the dangers of Uncle Sam.

PMID- 30091866
TI  - How going with the flow led to a better patient journey.
AB  - A new L60m hospital building was the catalyst for an improve system of patient
      flow that was to transform the public's experience of Morriston Hospital in
      Swansea.

PMID- 30091867
TI  - Are we prepared to pay more for healthcare?
AB  - Lost in the news on a big day for the Brexit saga was a sobering analysis of the
      NHS's long-term sustainability.

PMID- 30091871
TI  - Will the NHS never learn from tragic lessons of the past?
AB  - A patient safety campaigner gives his reaction to MPs' report on why the health
      service is still slow to make crucial changes.

PMID- 30091872
TI  - How a collaborative approach is Doing The Right Thing for place-based health and
      care.
AB  - How the voluntary sector can best contribute to health and care transformation
      was the focus of a Richmond Group of Charities seminar in London.

PMID- 30091873
TI  - The Nurses who Specialise in Savings.
AB  - Specialist nurses are far from just the 'icing on the cake' - in inflammatory
      bowel disease alone they are consistently preventing emergency attendances and
      ensuring the most appropriate use of services.

PMID- 30091874
TI  - Supporting Cost Effective Innovations in Treatment.
AB  - Specialist IBD nurses at key to ensuring cutting edge biological therapies are
      used in a way which benefits both trust and patient, as Claire Read explains.

PMID- 30091875
TI  - Bringing it All Back Home.
AB  - Shrewd service redesign by specialist nurses can lead to greater efficiency for
      providers and better care for patients.

PMID- 30091876
TI  - Support to Self Manage.
AB  - The support of a specialist nurse can equip IBD patients to better manage their
      condition, thereby reducing dependency on hospital services. Claire Read reports.

PMID- 30091877
TI  - [CANCER PATIENTS FOLLOW-UP - CROATIAN SOCIETY OF MEDICAL ONCOLOGY CLINICAL
      GUIDELINES Part I: breast cancer, uterine cancer, cervical cancer, ovarian
      cancer].
AB  - Treatment of oncological patients must be based upon multidisciplinary approach,
      and takes place in specialized oncological centers. By the end of a specific
      oncological treatment further follow-up is managed mostly by the -oncologists,
      but the role of the general practitioners becomes more important every day and
      therefore should be precisely defined. Nowadays, most of the existing follow-up
      guidelines are not based on prospective studies, but on the experts -opinion of a
      particular oncological center or specialists. The aim of the Croatian Society of
      Medical Oncology (CSMO) with these recommendations is to standardise and
      rationalise the diagnostic procedures algorithm in the follow-up of oncological
      patients after primary treatment.

PMID- 30091878
TI  - Multivalency regulates activity in an intrinsically disordered transcription
      factor.

PMID- 30091879
TI  - Back to the Drawing Board.
AB  - A misunderstanding of what 'human factors' means often leads organisations to try
      to change their people rather than the processes that could transform patient
      safety, finds Claire Read.

PMID- 30091880
TI  - Sepsis Faces a New Front.
AB  - Daloni Carlisle looks at how technology is helping clinicians to detect sepsis
      earlier, something which is key to combating this often undetected killer.

PMID- 30091881
TI  - [CANCER PATIENTS FOLLOW-UP - CROATIAN SOCIETY OF MEDICAL ONCOLOGY CLINICAL
      GUIDELINES Part II: renal cell cancer, urinary bladder cancer, prostate cancer,
      testicular cancer].
AB  - The treatment of oncological patients must be based upon multidisciplinary
      approach, and takes place in specialized oncological centers. By the end of a
      specific oncological treatment further follow-up is being managed mostly by the
      oncologists, but the role of the general practitioners becomes more important
      every day and therefore should be precisely defined. Nowadays, most of the
      existing follow-up guidelines are not based on prospective studies, but on the
      experts opinion of individual oncological centers or specialists. The aim of the
      Croatian Society of Medical Oncology (CSMO) with these recommendations is to
      standardize and rationalize the diagnostic procedures algorithm in the follow-up
      of -oncological patients after primary treatment, in patients with renal cell
      cancer, urinary bladder cancer, prostate cancer and testicular cancer.

PMID- 30091882
TI  - [CANCER PATIENTS FOLLOW-UP - CROATIAN SOCIETY OF MEDICAL ONCOLOGY CLINICAL
      GUIDELINES Part III: neuroendocrine neoplasms, hepatocellular carcinoma,
      pancreatic cancer, cancer of the bile ducts].
AB  - The treatment of oncological patients must be based upon multidisciplinary
      approach, and takes place in specialized oncological centers. By the end of a
      specific oncological treatment further follow-up is being managed mostly by the
      oncologists, but the role of the general practitioners becomes more important
      every day and therefore should be precisely defined. Nowadays, most of the
      existing follow-up guidelines are not based on prospective studies, but on the
      experts opinion of individual oncological centers or specialists. The aim of the
      Croatian Society of Medical Oncology (CSMO) with these recommendations is to
      standardize and rationalize the diagnostic procedures algorithm in the follow-up
      of oncological patients after primary treatment, in patients with neuroendocrine
      neoplasms, hepatocellular carcinoma, pancreatic cancer and cancer of the bile
      ducts.

PMID- 30091885
TI  - First Do No Harm.
AB  - Legal processes must never get in the way of supporting staff, reducing risks to
      patients and doing the right thing, says Helen Vernon of the NHS Litigation
      Authority.

PMID- 30091884
TI  - [SATISFACTION OF YOUNG DOCTORS IN CROATIA: ARE WE HEADING IN THE RIGHT
      DIRECTION]?
AB  - Introduction: The satisfaction of junior medical doctors is primarily associated
      with the training they receive during the residency period and working
      conditions. Given a considerable brain-drain of medical doctors from the Republic
      of Croatia, the present research focused on the evaluation of the satisfaction of
      junior medical doctors. Methodology: The Junior Doctors Committee of the Croatian
      Medical Chamber prepared a questionnaire on the satisfaction of junior doctors.
      The relevant questionnaire was available for filling in online in the period from
      February 1 to March 20, 2016. Results: The questionnaire was completed by 1,531
      persons aged between 29 and 35 (mean age 32) of which 67% were females. A 58% of
      respondents would leave the Republic of Croatia if offered an opportunity. The
      main reasons for leaving the country include better working conditions (74%),
      well-regulated healthcare system (64%) and higher wages (64%). In case of staying
      in the country, their future professional status and development would remain
      unaltered (44%). Conclusion: The questionnaire results show a high level of
      dissatisfaction with the healthcare system, some segments of the specialist
      training and the mentor role. The analysis of factors affecting the satisfaction
      of junior doctors will facilitate the preparation and adoption of measures aiming
      to mitigate the above-mentioned trend.

PMID- 30091886
TI  - Let Patient Experience Take Centre Stage.
AB  - What the patient experiences is a central pillar of healthcare quality - but much
      needs to be done to bring it to the forefront of the agenda, writes Helen Mooney.

PMID- 30091887
TI  - [EPIDEMIOLOGICAL CHARACTERISTICS OF TETANUS IN THE REPUBLIC OF CROATIA].
AB  - The aim of the study was to determine the epidemiological characteristics of
      tetanus in Croatia and to determine changes in the age and sex structure,
      morbidity and mortality after the introduction of mandatory immunization and
      after the introduction of additional immunization for persons aged >= 60. The
      retrospective study was undertaken and the data on the number of patients and
      deaths from tetanus in the period 1946-2014 in Croatia were analyzed. The data
      considering age, gender and geographical location of disease occurrence were also
      analyzed. The study confirmed the reduction of morbidity, mortality and fatality
      rate from tetanus after the introduction of mandatory immunization. In the last
      twenty years the average morbidity rate was 1.68/1 000 000 population. A higher
      incidence of tetanus was observed in female patients. During the last ten years
      all patients were in the age group of 60 and above. The distribution of patients
      according to the geographical location showed a higher incidence of tetanus in
      continental Croatia (26/31; 84%) than in coastal area. The less reported number
      occurred during the winter months. This preventive measure is very effective and
      economically justified.

PMID- 30091888
TI  - [CIGARETTE SMOKING AMONG SCHOOL ADOLESCENTS IN THE BRCKO DISTRICT OF BOSNIA AND
      HERZEGOVINA: A CROSS-SECTIONAL STUDY].
AB  - Objective: The objective of the study was to determine the prevalence of
      cigarette smoking in adolescents in public schools of the Brcko District of B&H
      in relation to their gender, age and place of residence. Participants and 
      Methods: A cross-sectional study, based on the ESPAD (European School Survey
      Project on Alcohol and Other Drugs) questionnaire adapted to this research
      comprised 4,188 respondents who attended primary and secondary schools. Data were
      collected using a questionnaire prepared for each respondent. Results:
      Significantly fewer respondents smoke cigarettes compared to those who do not (p
      < 0.001), while in relation to gender male adolescents smoke more often than
      female adolescents (p = 0.012). In relation to their place of residence it is
      established that a significantly higher number of respondents from rural areas
      smoke cigarettes compared to those from the city (p < 0.001). More than half of
      the respondents, who smoke regardless of their gender, had their first cigarette
      before the age of 13. Male adolescents often begin smoking before the age of
      thirteen compared to female adolescents (p < 0.001), while female adolescents
      often begin smoking between the ages of 15 and 16 in relation to male adolescents
      (p <0.001). Every second respondent who smokes cigarettes irrespective of his/her
      place of residence did so at the age of 13. However, the respondents from rural
      areas smoke more often (p < 0.0001). Out of 895 respondents who smoked during the
      last month, 259 of or 30.3 % smoked only one cigarette a week, 162 or 18.1 %
      smoked 1-5 cigarettes a day, 168 or 18.8 % of the respondents smoked 6-10
      cigarettes a day, 146 or 16.3 % smoked 11 to 20 cigarettes a day, and 160 or 17.9
      % of the respondents smoked every day. Conclusion: Although 42.8 % of the
      respondents who had ever smoked cigarettes is significantly less compared to 57.2
      % of the respondents who do not smoke, that number is disturbing since we talk
      about the vulnerable population group and the fact that every second adolescent
      started smoking at the age to 13.

PMID- 30091889
TI  - [THE SCALP AS A SPLIT-THICKNESS GRAFT DONOR IN THE TREATMENT OF A MASSIVE THERMAL
      INJURY].
AB  - We are presenting our initial experience with the utilization of the scalp as a
      donor for split thickness skin grafting in the treatment of massive thermal
      injuries. Rapid donor reepithelization, absence of hypertrophic scarring in the
      donor area, inconspicuous donor area and a large area for the procurement of
      grafts in the pediatric population are the advantages that are emphasized in the
      literature. The outcome in a 3-year-old boy who suffered a burn injury from an
      open fire in the family house on the 57% of his total body surface area (48% full
      thickness burn) showed that the "take rate", in the absence of a massive local
      infection, was around 80% and that the scalp can be utilized again as a donor
      area after a period of 14 days. Folliculitis and alopecia are complications that
      should be kept in mind when using this technique.

PMID- 30091890
TI  - Free-Standing Sandwich-Type Graphene/Nanocellulose/Silicon Laminar Anode for
      Flexible Rechargeable Lithium Ion Batteries.
AB  - Freely deformable and free-standing electrodes together with high capacity are
      crucial to realizing flexible Li-ion batteries. Herein, a lamellar
      graphene/nanocellulose/silicon (GN/NC/Si) film assembled by interpenetrated GN
      nanosheets is synthesized via a facile vacuum-assisted filtration approach
      accompanied by the covalent cross-linking effect of glutaraldehyde. The hybrid
      film consists of the highly conductive GN matrix as an effective current
      collector, hydroxylated silicon nanoparticles (Si NPs) embedded uniformly within
      GN interlayer and NC as adhesive to cross-link GN and Si NPs. When applied as
      anode, the GN/NC/Si film exhibits a high reversible capacity of 1251 mA h g-1 at
      100 mA g-1 after 100 cycles and superior rate capability. More importantly, in
      the stress-strain test, this film represents robust mechanical strength, which
      not only provides good flexibility but also accommodates volume change of Si
      during cycling. By coupling with lithium cobalt oxide as the cathode, the full
      cell successfully powers a light-emitting diode, even bended and folded,
      indicating the deformation-tolerant GN/NC/Si film electrode for flexible Li-ion
      batteries. Therefore, the design of layered nanocomposites will offer the
      possibility closer to the application of flexible batteries.

PMID- 30091891
TI  - Cobalt Complexes as an Emerging Class of Catalysts for Homogeneous
      Hydrogenations.
AB  - Catalytic hydrogenation using molecular hydrogen represents a green and practical
      approach for reductions of all kinds of organic chemicals. Traditionally, in the
      majority of these processes the presence of transition metal catalysts is
      required. In this regard, noble-metal-based catalysts have largely been
      implemented, such as the application of iridium, palladium, rhodium, ruthenium,
      and others. Recently, the employment of earth-abundant 3d metals has emerged to
      replace the utilization of scarce noble metals because of their availability,
      lower cost, and often reduced toxicity. In this respect, several cobalt
      complexes, in the form of either molecularly well-defined or in situ-formed
      complexes, are receiving increasing attention from the scientific community.
      Importantly, the stability and reactivity of the complexes have greatly been
      supported by multidentate ligands under steric and/or electronic influences. For
      instance, tridentate or tetradentate phosphine ligands indirectly tune the
      reactivity of the metal center to accelerate the overall process, whereas direct
      participation of the ligand in pincer-type complexes through ligand-metal
      cooperation regulates the elementary steps in the catalytic cycle. In this
      Account, we emphasize specifically the advancements in cobalt-catalyzed
      hydrogenations using molecular hydrogen accomplished in our group. A variety of
      substrate classes ranging from simple molecules (e.g., carbon dioxide) to complex
      compounds were explored under the mild and efficient catalytic conditions.
      Notable examples include the reduction of carbon dioxide to afford either
      formates using a Co(BF4)2.6H2O/Tetraphos catalyst system or methanol employing a
      Co(acac)3/Triphos complex in the presence of HNTf2. As interesting examples of
      the synthesis of fine chemicals, cobalt-promoted hydrogenations of nitriles to
      primary amines and reductive alkylations of indoles using carboxylic acids as
      alkylating agents are highlighted. Moreover, highly selective hydrogenations of N
      heteroarenes under additive-free conditions were possible by the application of
      specific cobalt complexes. More recently, a set of carboxylic esters could be
      hydrogenated to the corresponding alcohols with high efficiency by the use of a
      well-defined cobalt-PNP pincer catalyst. In particular, the decent reactivity of
      cobalt catalysts enabled high selectivity and functional group tolerance to be
      achieved. Throughout our studies, it was found that the pairing of a suitable
      cobalt precursor and an appropriate tridentate or tetradentate phosphine ligand
      plays a crucial role harnessing the desired reactivity, while other monodentate
      and bidentate phosphine ligands showed no reactivity in these investigations. Our
      developments could provide supervisory information for the future exploration of
      cobalt-catalyzed hydrogenation reactions and other types of reactions involving
      cobalt catalysis. Furthermore, relevant contributions from other groups,
      remaining challenges, and future perspectives in this research area are also
      presented.

PMID- 30091892
TI  - Additive Manufacturing of Honeybee-Inspired Microneedle for Easy Skin Insertion
      and Difficult Removal.
AB  - With natural evolution, honeybee stinger with microbarbs can easily penetrate and
      trap in the skin of hostile animals to inject venom for self-defense. We proposed
      a novel three-dimensional additive manufacturing method, namely
      magnetorheological drawing lithography, to efficiently fabricate a bioinspired
      microneedle imitating a honeybee stinger. Under the assistance of an external
      magnetic field, a parent microneedle was directly drawn on the pillar tip, and
      tilted microbarbs were subsequently formed on the four sides of the parent
      microneedle. Compared with the barbless microneedle, the microstructured barbs
      enable the bioinspired microneedle for easy skin insertion and difficult removal.
      The extraction-penetration force ratio of the bioinspired microneedle was triple
      that of the barbless microneedle. The stress concentration at the barbs helps to
      reduce the insertion force of the bioinspired microneedle by minimizing the
      frictional force, whereas it increases the adhesion force by interlocking the
      barbs in the tissue during retraction. Such finds may provide an inspiration for
      further design of barbed microtip-based microneedles for tissue adhesion,
      transdermal drug delivery, biosignal recording, and so on.

PMID- 30091893
TI  - Fe7S8 Nanoparticles Anchored on Nitrogen-Doped Graphene Nanosheets as Anode
      Materials for High-Performance Sodium-Ion Batteries.
AB  - Despite high sodium storage capacity and better reversibility, metal sulfides
      suffer from relatively low conductivity and severe volume change as anode
      materials of sodium-ion batteries (SIBs). Introducing a conductive carbon matrix
      is an efficient method to enhance their sodium storage performance. Herein, we
      present iron sulfide (Fe7S8) nanoparticles anchored on nitrogen-doped graphene
      nanosheets fabricated through a combined strategy of solvothermal and postheating
      process. The as-prepared composite exhibits appealing cycling stability (a high
      discharge capacity of 393.1 mA h g-1 over 500 cycles at a current density of 400
      mA g-1 and outstanding high-rate performance of 543 mA h g-1 even at 10 A g-1).
      Considering the excellent sodium storage performance, this composite is quite
      hopeful to become a potential candidate as anode materials for future SIBs.

PMID- 30091894
TI  - Anchoring Fe3O4 Nanoparticles on Carbon Nanotubes for Microwave-Induced Catalytic
      Degradation of Antibiotics.
AB  - Microwave-induced catalytic degradation is considered amongst the most efficient
      techniques to remove antibiotic such as chlortetracycline from contaminated
      water. Described here is a new microwave-induced oxidation catalyst based on
      carbon nanotubes (CNTs) decorated uniformly with nanoparticles of Fe3O4. The
      combination of dielectric loss and magnetic loss of the material contributed to
      its stronger microwave absorption and the ability to produce more "hot spots".
      These hot spots promoted the oxidation of common antibiotics such as
      chlortetracycline, tetracycline, and oxytetracycline under microwave irradiation.
      Experiments with the addition of scavenger showed that hydroxy radicals (*OH)
      together with superoxide radicals (*O2-) contributed to the antibiotics removal
      as well. The final degradation products included CO2 and NO3- as confirmed by
      mass spectroscopy and ion chromatography analyses. The results indicated that the
      Fe3O4/CNTs was an efficient catalyst for microwave-induced oxidation.

PMID- 30091895
TI  - Mechanochromic Stretchable Electronics.
AB  - Soft and stretchable electronics are promising for a variety of applications such
      as wearable electronics, human-machine interfaces, and soft robotics. These
      devices, which are often encased in elastomeric materials, maintain or adjust
      their functionality during deformation, but can fail catastrophically if extended
      too far. Here, we report new functional composites in which stretchable
      electronic properties are coupled to molecular mechanochromic function, enabling
      at-a-glance visual cues that inform user control. These properties are realized
      by covalently incorporating a spiropyran mechanophore within
      poly(dimethylsiloxane) to indicate with a visible color change that a strain
      threshold has been reached. The resulting colorimetric elastomers can be molded
      and patterned so that, for example, the word "STOP" appears when a critical
      strain is reached, indicating to the user that further strain risks device
      failure. We also show that the strain at color onset can be controlled by
      layering silicones with different moduli into a composite. As a demonstration, we
      show how color onset can be tailored to indicate a when a specified frequency of
      a stretchable liquid metal antenna has been reached. The multiscale combination
      of mechanochromism and soft electronics offers a new avenue to empower user
      control of strain-dependent properties for future stretchable devices.

PMID- 30091896
TI  - Cyclopentadienyl Ligands in Lanthanide Single-Molecule Magnets: One Ring To Rule
      Them All?
AB  - The discovery of materials capable of storing magnetic information at the level
      of single molecules and even single atoms has fueled renewed interest in the slow
      magnetic relaxation properties of single-molecule magnets (SMMs). The lanthanide
      elements, especially dysprosium, continue to play a pivotal role in the
      development of potential nanoscale applications of SMMs, including, for example,
      in molecular spintronics and quantum computing. Aside from their fundamentally
      fascinating physics, the realization of functional materials based on SMMs
      requires significant scientific and technical challenges to be overcome. In
      particular, extremely low temperatures are needed to observe slow magnetic
      relaxation, and while many SMMs possess a measurable energy barrier to reversal
      of the magnetization ( Ueff), very few such materials display the important
      properties of magnetic hysteresis with remanence and coercivity. Werner-type
      coordination chemistry has been the dominant method used in the synthesis of
      lanthanide SMMs, and most of our knowledge and understanding of these materials
      is built on the many important contributions based on this approach. In contrast,
      lanthanide organometallic chemistry and lanthanide magnetochemistry have
      effectively evolved along separate lines, hence our goal was to promote a new
      direction in single-molecule magnetism by uniting the nonclassical organometallic
      synthetic approach with the traditionally distinct field of molecular magnetism.
      Over the last several years, our work on SMMs has focused on obtaining a detailed
      understanding of why magnetic materials based on the dysprosium metallocene
      cation building block {Cp2Dy}+ display slow magnetic relaxation. Specifically, we
      aspired to control the SMM properties using novel coordination chemistry in a way
      that hinges on key considerations, such as the strength and the symmetry of the
      crystal field. In establishing that the two cyclopentadienyl ligands combine to
      provide a strongly axial crystal field, we were able to propose a robust magneto
      structural correlation for understanding the properties of dysprosium metallocene
      SMMs. In doing so, a blueprint was established that allows Ueff and the magnetic
      blocking temperature ( TB) to be improved in a well-defined way. Although
      experimental discoveries with SMMs occur more rapidly than quantitative theory
      can (currently) process and explain, a clear message emanating from the
      literature is that a combination of the two approaches is most effective. In this
      Account, we summarize the main findings from our own work on dysprosium
      metallocene SMMs, and consider them in the light of related experimental studies
      and theoretical interpretations of related materials reported by other
      protagonists. In doing so, we aim to contribute to the nascent and healthy debate
      on the nature of spin dynamics in SMMs and allied molecular nanomagnets, which
      will be crucial for the further advancement of this vibrant research field.

PMID- 30091897
TI  - Supramolecular Nanosystem Based on Pillararene-Capped CuS Nanoparticles for
      Targeted Chemo-Photothermal Therapy.
AB  - A smart supramolecular nanosystem integrating targeting, chemotherapy, and
      photothermal therapy was constructed based on carboxylatopillar[5]arene (CP[5]A)
      functionalized CuS nanoparticles (CuS@CP NPs). CuS@CP NPs with good
      monodispersibility and strong near-infrared absorption were synthesized in
      aqueous solution through a facile one-pot supramolecular capping method, followed
      by surface installation of a liver cancer-targeted galactose derivative through
      host-guest binding interaction. The resulting smart supramolecular nanosystem,
      namely, CuS@CPG, exhibited excellent photothermal ablation capability to HepG2
      cells upon irradiation with laser at 808 nm. Chemotherapeutic drug, doxorubicin
      hydrochloride (DOX), was further loaded on CuS@CPG via electrostatic interactions
      between positively charged DOX and negatively charged CP[5]A to give CuS@CPG-DOX
      with a high drug-loading capacity up to 48.4%. The weakening of DOX-CP[5]A
      interactions in an acidic environment promoted the pH-responsive drug release
      from CuS@CPG-DOX. Significantly, this multifunctional supramolecular nanosystem
      showed a remarkably enhanced therapeutic effect through the combination of
      targeted chemotherapy and photothermal therapy upon in vitro cell study.
      Moreover, preliminary in vivo study demonstrated that CuS@CPG and CuS@CPG-DOX had
      good biocompatibility and excellent tumor inhibition effects upon near-infrared
      laser irradiation.

PMID- 30091898
TI  - Direct MALDI-TOF MS Identification of Bacterial Mixtures.
AB  - Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is now widely used to characterize bacterial samples for clinical
      diagnosis, food safety control, environmental monitoring, and so on. However,
      existing standard approaches are only applied to analyze single colonies purified
      by plate culture, which limits the approaches to cultivable bacteria and makes
      the whole approaches time-consuming. In this work, we propose a new framework to
      analyze MALDI-TOF spectra of bacterial mixtures and to directly characterize each
      component without purification procedures. The framework is a combination of a
      synthetic mixture model based on a non-negative linear combination of candidate
      reference spectra and a statistical assessment by in silico generated spectra via
      a jackknife resampling. Ninety-seven model bacterial mixture samples and 8
      cocultured blind-coded bacterial mixture samples, containing up to 6 strains in
      varied ratios in each sample, together with a reference database containing the
      mass spectra of 1081 strains, were used to validate the framework. High
      sensitivity (>80%, with error rate <5%) was achieved for balanced binary and
      ternary mixtures. The sensitivity was >60% for balanced quaternary and pentabasic
      mixtures, and 48%-71% for asymmetric situation, with error rate <5%. The work can
      facilitate rapid and reliable characterization of bacterial mixtures without
      purification procedures, which is of practical value in clinical diagnosis, food
      safety control, environmental monitoring, and so on. The framework can be further
      applied to many other spectroscopy-based analytics to interpret spectra from
      mixed samples.

PMID- 30091899
TI  - Mycobacterial MenJ: An Oxidoreductase Involved in Menaquinone Biosynthesis.
AB  - MenJ, annotated as an oxidoreductase, was recently demonstrated to catalyze the
      reduction (saturation) of a single double bond in the isoprenyl side-chain of
      mycobacterial menaquinone. This modification was shown to be essential for
      bacterial survival in J774A.1 macrophage-like cells, suggesting that MenJ may be
      a conditional drug target in Mycobacterium tuberculosis and other pathogenic
      mycobacteria. Recombinant protein was expressed in a heterologous host, and the
      activity was characterized. Although highly regiospecific in vivo, the activity
      is not absolutely regiospecific in vitro; in addition, the enzyme is not specific
      for naphthoquinones vs benzoquinones. Coenzyme Q-1 (a benzoquinone, UQ-1) was
      used as the lipoquinone substrate, and NADH oxidation was followed
      spectrophotometrically as the activity readout. NADPH could not be substituted
      for NADH in the reaction mixture. The enzyme contains a FAD binding site that was
      72% occupied in the purified recombinant protein. Enzyme activity was maximal at
      37  degrees C and pH 7.0; addition of divalent cations, EDTA, and reducing agents
      such as dithiothreitol to the reaction mixture had no effect on activity. The
      addition of detergents did not stimulate activity, and addition of saturating
      levels of FAD had relatively little effect on the observed kinetic parameters.
      These properties allowed the development of a facile assay needed to study this
      potential drug target, which is also amenable to high throughput screening. The
      Km values for UQ-1 using recombinant MenJ from Mycobacterium smegmatis or M.
      tuberculosis without saturating concentrations of FAD were found to be 52 +/- 9.6
      and 44 +/- 4.8 MUM, respectively, while the KmNADH values were determined to be
      59 +/- 14 and 64 +/- 15 MUM. The Km for MK-1, the menaquinone analogue of UQ-1,
      using recombinant MenJ from M. tuberculosis without saturating concentrations of
      FAD but in the presence of 0.5% Tween 80 was shown to be 30 +/- 2.9 MUM. Thus,
      this is the first report of a kinetic characterization of a member of the
      geranylgeranyl reductase family of enzymes.

PMID- 30091900
TI  - Food-Induced Increase of Acetylcholine in Mouse Hypothalamus.
AB  - Using microdialysis in C57Bl6 mice, we monitored cholinergic activity in the
      hypothalamus. Food intake after an overnight fast caused a 3-fold increase of
      extracellular acetylcholine (ACh) concentrations in the hypothalamus. The effect
      lasted for about 30 min. Food containing no calories (kaolin pellets), or food
      that was presented but not accessible, also increased ACh release. In contrast,
      injections of glucose or beta-hydroxybutyrate did not change extracellular ACh.
      Mice deficient in muscarinic M3 receptors had the same cholinergic response as
      wild-type mice. We conclude that the increase of ACh in the hypothalamus was not
      caused by local detection of nutrients but by anticipation of food intake. This
      suggests the involvement of motivational circuits in the basal forebrain which is
      reinforced by the fact that we found slight increases of ACh in the nucleus
      accumbens during feeding.

PMID- 30091901
TI  - Self-Assembled Minimalist Multifunctional Theranostic Nanoplatform for Magnetic
      Resonance Imaging-Guided Tumor Photodynamic Therapy.
AB  - Minimalist multifunctional platforms for delivering diagnostic and therapeutic
      agents effectively and safely into tumor sites are highly desired in
      nanomedicine. Herein, we describe the fabrication of a supramolecular
      nanoplatform via the amphiphilic amino acid (9-fluorenylmethyloxycarbonyl-l
      leucine, Fmoc-l-L)-modulated self-assembly of a magnetic resonance imaging (MRI)
      contrast agent (ionic manganese, Mn2+) and photosensitive drug (chlorin e6, Ce6).
      Coordination drives the coassembly of Fmoc-l-L and Mn2+ to generate a nanoscale
      supramolecular network to adaptively encapsulate Ce6. The obtained biometal
      organic nanoparticles exhibit a high drug loading capability, inherent good
      biocompatibility, robust stability, and smart disassembly in response to
      glutathione (GSH). The cooperative assembly of the multiple components is
      synchronously dynamic in nature and enables enhanced photodynamic therapy (PDT)
      to damage tumor cells and tissue by efficiently delivering the photosensitizer
      and improving the reductive tumor microenvironment via the competitive
      coordination of GSH with Mn2+. The antitumor effect can also be monitored and
      evaluated in vivo by MRI through the long-term intracellular biochelation of
      Mn2+. Therefore, this work presents a one-pot and robust method for the self
      assembly of a multifunctional theranostic nanoplatform capable of MRI-guided PDT
      starting from minimalist biological building blocks.

PMID- 30091902
TI  - Reverse Binding Mode of Phosphotyrosine Peptides with SH2 Protein.
AB  - Discerning the different interaction states during dynamic protein-ligand binding
      is difficult. Here we apply site-specific cysteine-alpha-chloroacetyl cross
      linking to scrutinize the binding between the Src homology 2 (SH2) domain and
      phosphotyrosine (pY) peptides, a highly dynamic interaction that is a key to
      cellular signal transduction. From a model SH2 protein to a set of representative
      SH2 domains, we showed here that a proximity-induced cysteine-alpha-chloroacetyl
      reaction cross-linked two spatially adjacent chemical groups as a result of the
      binding interaction, and reciprocally, the information about the interaction
      states can be deduced from the cross-linked products. To our surprise, we found
      SH2 domains can adopt a reverse binding mode with "single-pronged", "two
      pronged", and "half" pY peptides. This finding was further supported by a set of
      500 ns molecular dynamics simulations. This serendipitous finding defies the
      canonical theory of SH2 binding, suggests a possible answer about the source of
      the versatility of SH2 signaling, and sets a model for other protein binding
      interactions.

PMID- 30091903
TI  - Purification-Free MicroRNA Detection by Using Magnetically Immobilized Nanopores
      on Liposome Membrane.
AB  - MicroRNAs have critical roles in a number of serious diseases and, as a result,
      are of major interest as clinical diagnostic targets. Conventionally, microRNAs
      are collected from blood and urine samples and are measured by either
      quantitative reverse-transcription polymerase chain reaction or microarray.
      Recently, nanopore sensing techniques have been applied for measuring microRNAs
      at the single-molecule level. However, existing techniques are technically
      complex, needing several tools and requiring purification and/or labeling of
      microRNA samples prior to use. Here we report a method for microRNA detection in
      a simple procedure requiring neither purification nor labeling. This system
      utilizes magnetic beads anchored with DNA and nanopores on a liposome membrane.
      In the presence of the target microRNA, it forms a duplex with complementary DNA,
      which is then cleaved by a duplex-specific nuclease (DSN). The cleaved DNA, which
      harbors a liposome on its terminus, is subsequently released from the magnetic
      bead, fuses to the lipid bilayer on chip, and emits an electrical signal derived
      from the formation of a nanopore. Because of a property of the DSN, the signals
      derived from microRNAs are expected to be amplified in an isothermal reaction.
      Our system possesses the specificity to detect target microRNAs from mixtures
      containing >106 different microRNA sequences and readily uses blood or urine
      samples. Although the limit of detection is above 10 nM and needs to be improved
      for practical diagnosis, because purification and labeling are not required, the
      presented system proposes a possible schematic for the development of easy and on
      site diagnosis.

PMID- 30091904
TI  - Influence of Rock Mineralogy on Reactive Fracture Evolution in Carbonate-Rich
      Caprocks.
AB  - Fractures present environmental risks for subsurface engineering activities, such
      as geologic storage of greenhouse gases, because of the possibility of unwanted
      upward fluid migration. The risks of fluid leakage may be exacerbated if
      fractures are subjected to physical and chemical perturbations that alter their
      geometry. This study investigated this by constructing a 2D fracture model to
      numerically simulate fluid flow, acid-driven reactions, and mechanical
      deformation. Three rock mineralogies were simulated: a limestone with 100%
      calcite, a limestone with 68% calcite, and a banded shale with 34% calcite. One
      might expect transmissivity to increase fastest for rocks with more calcite due
      to its high solubility and fast reaction rate. Yet, results show that initially
      transmissivity increases fastest for rocks with less calcite because of their
      ability to deliver unbuffered-acid downstream faster. Moreover, less reactive
      minerals become persistent asperities that sustain mechanical support within the
      fracture. However, later in the simulations, the spatial pattern of less reactive
      mineral, not abundance, controls transmissivity evolution. Results show that a
      banded mineral pattern creates persistent bottlenecks, prevents channelization,
      and stabilizes transmissivity. For sites for geologic storage of CO2 that have
      carbonate caprocks, banded mineral variation may limit reactive evolution of
      fracture transmissivity and increase storage reliability.

PMID- 30091905
TI  - Small-Molecule Probes for Affinity-Guided Introduction of Biocompatible Handles
      on Metal-Binding Proteins.
AB  - Protein conjugates of high heterogeneity may contain species with significantly
      different biological properties, and as a consequence, the focus on methods for
      production of conjugates of higher quality has increased. Here, we demonstrate an
      efficient and generic approach for the modification of metal-binding proteins
      with biocompatible chemical handles without the need for genetic modifications.
      Affinity-guided small-molecule probes are developed for direct conjugation to off
      the-shelf proteins and for installing different chemical handles on the protein
      surface. While purification of protein conjugates obtained by small molecule
      conjugation is troublesome, the affinity motifs of the probes presented here
      allow for purification of the conjugates. The versatility of the probes is
      demonstrated by conjugation to several His-tagged and natural metal-binding
      proteins, including the efficient and area-selective conjugation to three
      therapeutically relevant antibodies.

PMID- 30091906
TI  - Dioxygen Activation on Cu-MOR Zeolite: Theoretical Insights into the Formation of
      Cu2O and Cu3O3 Active Species.
AB  - The utilization of low-cost and abundant oxygen (O2) as an oxidant in the
      activation of copper-exchanged zeolites is highly important for the direct,
      selective oxidation of methane to methanol at low temperatures. While two motifs
      of active sites, i.e., the [Cu2(MU-O)]2+ and [Cu3(MU-O)3]2+, have been
      experimentally observed in mordenite (MOR) zeolite, the mechanisms of their
      formation from the reaction of Cu-MOR with O2 are still unclear. In this study,
      we performed density functional theory (DFT) calculations for O2 activation over
      2[Cu2]2+-MOR and [Cu3O]2+-MOR zeolites. For the reaction on the dicopper species,
      we found two possible reaction routes: O-O bond cleavage leading to (1) formation
      of a [Cu2(MU-O)]2+ active species and a trans-MU-1,2-peroxo-Si2 species and (2)
      simultaneous formation of two [Cu2(MU-O)]2+ active species neighboring to each
      other. These routes are both exothermic but require completely different O-O bond
      activation energies. For the reaction on the tricopper species, we suggest a
      peroxo-Cu3O species as the intermediate structure with two transition states
      (TSs) involved in the reaction. The first TS where a significant rearrangement of
      the tricopper site occurs is found to be rate-determining, while the second TS
      where the peroxo bond is cleaved results in a smaller activation barrier. This
      reaction, in contrast to the dicopper case, is slightly endothermic. The present
      study provides theoretical insights that may help design of better Cu-exchanged
      zeolite catalysts for methane hydroxylation to methanol.

PMID- 30091907
TI  - Asymmetric Allylic C-H Alkylation via Palladium(II)/ cis-ArSOX Catalysis.
AB  - We report the development of Pd(II)/ cis-aryl sulfoxide-oxazoline ( cis-ArSOX)
      catalysts for asymmetric C-H alkylation of terminal olefins with a variety of
      synthetically versatile nucleophiles. The modular, tunable, and oxidatively
      stable ArSOX scaffold is key to the unprecedented broad scope and high
      enantioselectivity (37 examples, avg. > 90% ee). Pd(II)/ cis-ArSOX is unique in
      its ability to effect high reactivity and catalyst-controlled
      diastereoselectivity on the alkylation of aliphatic olefins. We anticipate that
      this new chiral ligand class will find use in other transition metal catalyzed
      processes that operate under oxidative conditions.

PMID- 30091908
TI  - Excited-State Planarization in Donor-Bridge Dye Sensitizers: Phenylene versus
      Thiophene Bridges.
AB  - Donor-pi-acceptor complexes for solar energy conversion are commonly composed of
      a chomophore donor and a semiconductor nanoparticle acceptor separated by a pi
      bridge. The electronic coupling between the donor and acceptor is known to be
      large when the pi systems of the donor and bridge are coplanar. However, the
      accessibility of highly coplanar geometries in the excited state is not well
      understood. In this work, we clarify the relationship between the bridge
      structure and excited-state donor-bridge coplanarization by comparing rhodamine
      sensitizers with either phenylene (O-Ph) or thiophene (O-Th) bridge units. Using
      a variety of optical spectroscopic and computational techniques, we model the S1
      excited-state potential surfaces of O-Ph and O-Th along the dihedral coordinate
      of donor-bridge coplanarization, tau. We find that O-Th accesses a nearly
      coplanar (tau = 8 degrees ) global minimum geometry in S1 where significant
      intramolecular charge transfer (ICT) character is developed. The S1 coplanar
      geometry is populated in <10 ps and is stable for ca. 1 ns. Importantly, O-Ph is
      sterically hindered from rotation along tau and therefore remains at its initial
      S1 equilibrium geometry far from coplanarity (tau = 56 degrees ). Our results
      demonstrate that donor-bridge dye sensitizers utilizing thiophene bridges should
      facilitate strong donor-acceptor coupling by an ultrafast and stabilizing
      coplanarization mechanism in S1. The coplanarization will result in strong donor
      acceptor coupling, potentially increasing the electron transfer efficiency. These
      findings provide further explanation for the success of thiophene as a bridge
      unit and can be used to guide the informed design of new molecular sensitizers.

PMID- 30091909
TI  - Catalytic Hydrothiolation: Regio- and Enantioselective Coupling of Thiols and
      Dienes.
AB  - We report a Rh-catalyzed hydrothiolation of 1,3-dienes, including petroleum
      feedstocks. Either secondary or tertiary allylic sulfides can be generated from
      the selective addition of a thiol to the more substituted double bond of a diene.
      The catalyst tolerates a wide range of functional groups, and the loading can be
      as low as 0.1 mol %.

PMID- 30091910
TI  - Long-Term Plastic Greenhouse Cultivation Changes Soil Microbial Community
      Structures: A Case Study.
AB  - Plastic greenhouse vegetable cultivation (PGVC) has been widely developed around
      the world and has resulted in great changes in soil properties and potential
      contamination by phthalate esters (PAEs). Using high-throughput sequencing, this
      study investigated the succession and potential factors impacting soil microbial
      community structures over 20 years of PGVC. The results showed that the pH of
      soils under PGVC were significantly lower, while the nutrient contents of soils
      were higher, relative to those of open field soil. The residue concentrations of
      PAEs in soil under PGVC increased with increasing periods of PGVC. The fungal
      community diversity, rather than the bacterial community diversity, was
      significantly reduced in soils under PGVC. However, both the soil bacterial and
      fungal community structures were changed by long-term PGVC. Among the tested soil
      physicochemical properties, soil pH and clay were the top two factors affecting
      the soil bacterial community, while pH and phosphorus (P) mainly affected the
      soil fungal community structures. No relationship between the changes of
      microbial communities and PAE residues in soil was observed. This study indicates
      that the soil acidification and nutrient accumulation under PGVC mainly shifted
      the changes of soil microbial community structures, which could occur after only
      5 years of PGVC.

PMID- 30091912
TI  - Photoinduced Deaminative Borylation of Alkylamines.
AB  - An operationally simple deaminative borylation reaction of primary alkylamines
      has been developed. The formation of electron-donor-acceptor complexes between N
      alkylpyridinium salts and bis(catecholato)diboron enables photoinduced single
      electron transfer and fragmentation to carbon-centered radicals, which are
      subsequently borylated. The mild conditions allow a diverse range of readily
      available alkylamines to be efficiently converted into synthetically valuable
      alkylboronic esters under catalyst-free conditions.

PMID- 30091911
TI  - Intersystem Crossing as a Key Component of the Nonadiabatic Relaxation Dynamics
      of Bithiophene and Terthiophene.
AB  - We present a nonadiabatic dynamics study concerning the subpicosecond relaxation
      of excited states in dimeric and trimeric thiophene chains. The influence of the
      triplet states in the overall process is, for the first time, taken into account
      by explicitly including spin-orbit couplings and hence allowing intersystem
      crossing phenomena. We observe the fundamental role of the triplet state manifold
      in driving the full relaxation process. In particular we evidence the effect of
      both, inter-ring rotation and ring-opening, in the process, as compared to the
      monomer, where the ring-opening process appears as the dominant one. In addition,
      the evolution of the open structures allows for trans to cis isomerization in the
      dimer and trimer. The overall relaxation process slows down with chain
      elongation. The complex decay mechanism characterized by the presence of
      different competing channels, due to the presence of a quasi degenerate manifold,
      is explained allowing the rationalization of oligothiophenes photophysics.

PMID- 30091913
TI  - Selective Sensing of Peroxynitrite by Hf-Based UiO-66-B(OH)2 Metal-Organic
      Framework: Applicability to Cell Imaging.
AB  - The first boronic acid functionalized Hf-based UiO-66 (UiO = University of Oslo)
      metal-organic framework (MOF) having the ability to detect both extracellular and
      intracellular peroxynitrite is presented. The Hf-UiO-66-B(OH)2 material (1) was
      synthesized under solvothermal conditions from a mixture of HfCl4 and 2-borono
      1,4-benzenedicarboxylic acid [H2BDC-B(OH)2] ligand in DMF in the presence of
      formic acid (modulator) at 130  degrees C for 48 h. The desolvated material (1')
      was utilized as a fluorescent turn-on probe for the rapid sensing of
      extracellular peroxynitrite (ONOO-) under conditions mimicking those of
      biological medium (10 mM HEPES buffer, pH 7.4). Selective sensing of ONOO- over
      other ROS/RNS was also achieved by 1'. The oxidative cleavage of attached boronic
      acid groups forming corresponding hydroxy-functionalized ligands can be accounted
      for the fluorescent increment phenomenon in the presence of ONOO-. The probe
      showed extraordinary sensitivity (detection limit = 9.0 nM) toward ONOO- in 10 mM
      HEPES buffer at pH 7.4. Probe-loaded cells did not exhibit cytotoxicity and
      morphological deformities. It is remarkable that the probe inside the cells
      responded toward the peroxynitrite solution to give an intense blue fluorescent
      signal. The fluorescence microscopy study with J774A.1 macrophage cells
      unambiguously demonstrated that probe 1' is suitable to image peroxynitrite in
      living cells.

PMID- 30091914
TI  - Enhanced 2- O-alpha-d-Glucopyranosyl-l-ascorbic Acid Synthesis through Iterative
      Saturation Mutagenesis of Acceptor Subsite Residues in Bacillus
      stearothermophilus NO2 Cyclodextrin Glycosyltransferase.
AB  - Low synthesis yields of the l-ascorbic acid (l-AA) derivative 2- O-alpha-d
      glucopyranosyl-l-ascorbic acid (AA-2G) limit its application in the food
      industry. In this work, the AA-2G synthesis yield of Bacillus stearothermophilus
      NO2 cyclodextrin glycosyltransferase (CGTase) was improved. Nine residues within
      10 A of the catalytic residue Glu253 displaying <=30% conservation and located in
      the acceptor subsite were selected for iterative saturation mutagenesis. The best
      mutant, K228R/M230L, produced a higher AA-2G yield with maltodextrin as the
      glucosyl donor than that produced by its parent wild-type. The l-AA Km values of
      the mutant K228R/M230L decreased by 35%, whereas the kcat/ Km increased by 2.69
      fold. Kinetic analysis indicated that K228R/M230L displayed enhanced l-AA
      specificity. These results demonstrate that acceptor subsite residues play an
      important role in acceptor substrate specificity. Mutant K228R/M230L afforded the
      highest AA-2G concentration (211 g L-1, 624 mM) reported to date after
      optimization of the reaction conditions.

PMID- 30091915
TI  - Development of Second-Generation CDK2 Inhibitors for the Prevention of Cisplatin
      Induced Hearing Loss.
AB  - There are currently no FDA-approved therapies to prevent the hearing loss
      associated with the usage of cisplatin in chemotherapeutic regimens. We recently
      demonstrated that the pharmacologic inhibition with kenpaullone or genetic
      deletion of CDK2 preserved hearing function in animal models treated with
      cisplatin, which suggests that CDK2 is a promising therapeutic target to prevent
      cisplatin-induced ototoxicity. In this study, we identified two lead compounds,
      AT7519 and AZD5438, from a focused library screen of 187 CDK2 inhibitors,
      performed in an immortalized cell line derived from neonatal mouse cochleae
      treated with cisplatin. Moreover, we screened 36 analogues of AT7519 and
      identified analogue 7, which exhibited an improved therapeutic index. When
      delivered locally, analogue 7 and AZD5438 both provided significant protection
      against cisplatin-induced ototoxicity in mice. Thus, we have identified two
      additional compounds that prevent cisplatin-induced ototoxicity in vivo and
      provided further evidence that CDK2 is a druggable target for treating cisplatin
      induced ototoxicity.

PMID- 30091916
TI  - Photophysical and Photobiological Properties of Dinuclear Iridium(III) Bis
      tridentate Complexes.
AB  - A series of cationic dinuclear iridium(III) complexes (Ir1-Ir5) bearing
      terpyridine-capped fluorenyl bridging ligands and different polypyridyl or
      cyclometalating terminal tridentate ligands were synthesized, characterized, and
      evaluated for their photophysical and photobiological activities. The influence
      of the bridging and terminal ligands on the photophysical properties of the
      complexes was investigated by UV-vis absorption, emission, and transient
      absorption spectroscopy and simulated by TDDFT calculations. All of the complexes
      displayed strong bridging-ligand localized visible 1pi,pi* absorption and red- or
      near-infrared phosphorescence as well as broad triplet excited-state absorption
      across both visible and NIR wavelengths. These triplet states were assigned as
      predominantly 3pi,pi* for Ir1 (tau = 3.1 MUs) and Ir4 (tau = 48 MUs) and 3CT
      (charge transfer) for Ir2, Ir3, and Ir5 (tau = 1.7-2.7 MUs). Complexes Ir1-Ir5
      acted as in vitro photodynamic therapy (PDT) agents toward human SK-MEL-28
      melanoma cells when activated with visible light, with submicromolar
      photocytotoxicity and phototherapeutic indices ranging from 20 to almost 300. The
      in vitro PDT effects with visible light did not correlate with singlet oxygen
      (1O2) quantum yields or DNA photocleaving capacity probed under cell-free
      conditions. All of the Ir(III) complexes phosphoresced brightly when associated
      with compromised cells (with or without light treatment) and exhibited
      photoactivated cellular uptake, highlighting the theranostic potential of this
      new class of Ir(III) complex photosensitizers.

PMID- 30091917
TI  - Dynamics of Liquid Oil that Flows Inside Aqueous Wet Foam.
AB  - Wet soap foam spontaneously imbibes liquid oil without defoaming when it is
      brought into contact. The kinetics behind this recently observed phenomenon was
      studied experimentally, with focus on the origin of the suction force and on the
      oil front dynamics. Using an aqueous foam with an air volume fraction slightly
      greater than the critical value phiC, we show that the pumping pressure of oil
      and/or miscible liquid into the wet foam is attributed to the interfacial
      distortion of the bubble surfaces. Two distinct regimes along time t were
      observed in the oil imbibition dynamics. The proceeding oil front evolves with
      t1/2 dependency in the early imbibition time in accordance with the classical
      theory of penetration of a porous medium, whereas it departs into t1/3 at late
      imbibition time. The latter process is attributed to the elongation of an oil
      branch trapped inside the foam when pumping of the exterior oil has ceased.

PMID- 30091918
TI  - Correction to Ochratoxin A-Induced Apoptosis of IPEC-J2 Cells through ROS
      Mediated Mitochondrial Permeability Transition Pore Opening Pathway.

PMID- 30091919
TI  - Elastically Collective Nonlinear Langevin Equation Theory of Glass-Forming
      Liquids: Transient Localization, Thermodynamic Mapping, and Cooperativity.
AB  - We analyze multiple new issues concerning activated relaxation in glassy hard
      sphere fluids and molecular and polymer liquids based on the elastically
      collective nonlinear Langevin equation (ECNLE) theory. By invoking a high
      temperature reference state, a near universality of the apparent dynamic
      localization length scale is predicted for liquids of widely varying fragility, a
      result that is relevant to recent simulation studies and quasi-elastic neutron
      scattering measurements. In contrast, in the same format, a strongly nonuniversal
      behavior is found for the activation barrier that controls long-time relaxation.
      Two measures of cooperativity in the ECNLE theory are analyzed. A particle-level
      total displacement associated with the alpha relaxation event is found to be only
      of order 1-2 particle diameters and weakly increases with cooling. In contrast,
      an alternative cooperativity length is defined as the spatial scale required to
      essentially recover the full barrier and bulk alpha time. This length scale grows
      strongly with cooling because of the emergence in the deeply supercooled regime
      of collective long-range elastic fluctuations required to allow local hopping. It
      becomes very large as the laboratory Tg is approached, though it is relatively
      modest at degrees of supercooling accessible with molecular dynamics simulation.
      The alpha time is found to be exponentially related to this cooperativity length
      over an enormous number of decades of relaxation time that span the lightly to
      deeply supercooled regimes. Moreover, the effective barrier height increases
      almost linearly with the growing cooperativity length scale. An alternative
      calculation of the collective elastic barrier based on a literal continuum
      mechanics approach is shown to result in very little change of the theoretical
      results for bulk properties but leads to a much smaller and less temperature
      sensitive cooperativity length scale.

PMID- 30091920
TI  - Discovery of a Potent and Selective Steroidal Glucocorticoid Receptor Antagonist
      (ORIC-101).
AB  - The glucocorticoid receptor (GR) has been linked to therapy resistance across a
      wide range of cancer types. Preclinical data suggest that antagonists of this
      nuclear receptor may enhance the activity of anticancer therapy. The first
      generation GR antagonist mifepristone is currently undergoing clinical evaluation
      in various oncology settings. Structure-based modification of mifepristone led to
      the discovery of ORIC-101 (28), a highly potent steroidal GR antagonist with
      reduced androgen receptor (AR) agonistic activity amenable for dosing in androgen
      receptor positive tumors and with improved CYP2C8 and CYP2C9 inhibition profile
      to minimize drug-drug interaction potential. Unlike mifepristone, 28 could be
      codosed with chemotherapeutic agents readily metabolized by CYP2C8 such as
      paclitaxel. Furthermore, 28 demonstrated in vivo antitumor activity by enhancing
      response to chemotherapy in the GR+ OVCAR5 ovarian cancer xenograft model.
      Clinical evaluation of safety and therapeutic potential of 28 is underway.

PMID- 30091922
TI  - Reductive Deuteration of Nitriles: The Synthesis of alpha,alpha-Dideuterio Amines
      by Sodium-Mediated Electron Transfer Reactions.
AB  - The first general reductive deuteration of nitriles under single-electron
      transfer conditions has been developed for the synthesis of alpha,alpha
      dideuterio amines. This practical and cost-efficient protocol requires only bench
      stable and commercially available sodium dispersions and EtOD- d1 and allows for
      the reductive deuteration of a variety of nitriles in excellent yields and
      deuterium incorporations.

PMID- 30091921
TI  - Explicit Aqueous Solvation Treatment of Epinephrine from Car-Parrinello Molecular
      Dynamics: Effect of Hydrogen Bonding on the Electronic Absorption Spectrum.
AB  - The electronic absorption spectrum of the neurotransmitter epinephrine (EPN) in
      water solution is studied, combining ab initio Car-Parrinello molecular dynamics
      (CPMD) with a quantum mechanical approach within the framework of the time
      dependent density functional theory (TDDFT) scheme. By selecting 52 uncorrelated
      snapshots, the excitation modes were calculated at the LC-omegaPBE/6-31+G(d)
      level of theory, using an optimal range-separation parameter omega, determined by
      means of the gap-tuning scheme in the presence of the solvent molecules. By
      comparing with static approaches (vacuum and implicit solvation), we show here
      that explicit solvation treatment dramatically enhances the photophysical
      properties of the EPN, especially because of the more realistic dynamic
      description of the molecular geometry. The agreement between the simulated and
      experimental spectra is demonstrated when TDDFT calculations are performed with
      the optimally tuned version of the DFT hybrid, not only improving the relative
      intensities of the absorption bands but also the lambdamax position. These
      results highlight that accounting for the nuclear motions, that is, thermal
      effects (of both chromophore and solvent molecules), is imperative to predict
      experimental absorption spectra. In this paper, we have addressed the critical
      importance of explicit solvation effects on the photophysics of the EPN, raking
      in performance when the simulation is performed based on first-principles
      molecular dynamics such as CPMD.

PMID- 30091923
TI  - A Single Model for the Excited-State Dynamics of Au18(SR)14 and Au25(SR)18
      Clusters.
AB  - Excited-state properties of photonic materials play an important part in
      dictating the photocatalytic activity. Thiol-protected gold clusters, like
      Au18(SR)14 and Au25(SR)18, are an emerging material of interest with unique
      optical and electronic properties. Au18(SR)14 clusters, in particular, have shown
      promise as one of the highest efficiency clusters in light harvesting, with a
      high emission quantum yield. In this work, the excited-state properties of
      Au18(SR)14 are studied in-depth by ultrafast pump/probe spectroscopy for the
      first time. A single model describing the optical characteristics of thiol
      protected Au18(SR)14 and Au25(SR)18 clusters is offered. Excited-state dynamics
      analysis suggests that there are state-resolved relaxations due to the presence
      of multiple excited states. The populations of these excited states are shown to
      be solvent- and ligand-dependent.

PMID- 30091924
TI  - AWSEM-IDP: A Coarse-Grained Force Field for Intrinsically Disordered Proteins.
AB  - The associative memory, water-mediated, structure and energy model (AWSEM) has
      been successfully used to study protein folding, binding, and aggregation
      problems. In this work, we introduce AWSEM-IDP, a new AWSEM branch for simulating
      intrinsically disordered proteins (IDPs), where the weights of the potentials
      determining secondary structure formation have been finely tuned, and a novel
      potential is introduced that helps to precisely control both the average extent
      of protein chain collapse and the chain's fluctuations in size. AWSEM-IDP can
      efficiently sample large conformational spaces, while retaining sufficient
      molecular accuracy to realistically model proteins. We applied this new model to
      two IDPs, demonstrating that AWSEM-IDP can reasonably well reproduce higher
      resolution reference data, thus providing the foundation for a transferable IDP
      force field. Finally, we used thermodynamic perturbation theory to show that, in
      general, the conformational ensembles of IDPs are highly sensitive to fine-tuning
      of force field parameters.

PMID- 30091926
TI  - Shape Transformations of Vesicles Self-Assembled from Amphiphilic Hyperbranched
      Multiarm Copolymers via Simulation.
AB  - The understanding of shape transformations of vesicles is of fundamental
      importance in biological and clinical sciences. Hyperbranched polymer vesicles
      (branched polymersomes) are newly emerging polymer vesicles with special
      structure and property. They have also been regarded as a good model for
      biomembranes. However, the shape transformations of hyperbranched polymer
      vesicles have not been studied from either an experimental or theoretical level.
      Herein, the shape transformations of vesicles self-assembled from amphiphilic
      hyperbranched multiarm copolymers (HMCs) in response to the interaction
      parameters between the hydrophobic core and hydrophilic arms and the polymer
      concentrations are investigated carefully through dissipative particle dynamics
      (DPD) simulations. In the morphological phase diagram, two types of vesicles are
      obtained: one type corresponds to vesicles without holes formed at low
      concentrations including unilamellar vesicles, double-lamellar vesicles,
      discocyte-shaped vesicles, and tubular vesicles, and the other type corresponds
      to vesicles with holes formed at high concentrations including stomatocyte-shaped
      vesicles, toroidal vesicles, genus-3 (G-3) toroidal vesicles with three holes,
      and genus-4 (G-4) toroidal vesicles with four holes. In addition, both the self
      assembly mechanisms and the dynamics for the formation of these vesicles have
      been systematically studied. The current work will offer theoretical support for
      fabricating novel vesicles with various shapes from hyperbranched polymers.

PMID- 30091925
TI  - Ron Receptor Signaling Ameliorates Hepatic Fibrosis in a Diet-Induced
      Nonalcoholic Steatohepatitis Mouse Model.
AB  - Liver fibrosis is commonly observed in the terminal stages of nonalcoholic
      steatohepatitis (NASH) and with no specific and effective antifibrotic therapies
      available, this disease is a major global health burden. The MSP/Ron receptor
      axis has been shown to have anti-inflammatory properties in a number of mouse
      models, due at least in part, to its ability to limit pro-inflammatory responses
      in tissue-resident macrophages and hepatocytes. In this study, we established the
      role of the Ron receptor in steatohepatitis-induced hepatic fibrosis using Ron
      ligand domain knockout mice on an apolipoprotein E knockout background (DKO).
      After 18 weeks of high-fat high-cholesterol feeding, loss of Ron activation
      resulted in exacerbated NASH-associated steatosis which is precedent to
      hepatocellular injury, inflammation and fibrosis. 1H nuclear magnetic resonance
      (NMR)-based metabolomics identified significant changes in serum metabolites that
      can modulate the intrahepatic lipid pool in hepatic steatosis. Serum from DKO
      mice had higher concentrations of lipids, VLDL/LDL and pyruvate, whereas glycine
      levels were reduced. Parallel to the aggravated steatohepatitis, increased
      accumulation of collagen, inflammatory immune cells and collagen producing
      myofibroblasts were seen in the livers of DKO mice. Gene expression profiling
      revealed that DKO mice exhibited elevated expression of genes encoding Ron
      receptor ligand MSP, collagens, ECM remodeling proteins and pro-fibrogenic
      cytokines in the liver. Our results demonstrate the protective effects of Ron
      receptor activation on NASH-induced hepatic fibrosis.

PMID- 30091927
TI  - Wet Sunscreens in the Gas Phase: Structures of Isolated and Microsolvated
      Oxybenzone.
AB  - New insights into the structural intricacies of solvated sunscreen compounds are
      presented. Using high-resolution rotational spectroscopy with supersonic jets and
      quantum-chemistry calculations, we navigate the conformational space of
      oxybenzone and oxybenzone-water clusters. We unambiguously assign the global
      minimum structure, resolving any prevailing ambiguities, and locate the primary
      hydration sites of the ground-state enol conformer. Two microsolvated molecular
      models of oxybenzone are validated by rotational spectroscopy of isotopically
      enriched species. Theoretical predictions based on these models suggest that
      water influences the ground-state enol-keto energetic constraints and that its
      effect is biased depending on which water docking-site is at play.

PMID- 30091928
TI  - Ultrafast Electron Trapping and Defect-Mediated Recombination in NiO Probed by
      Femtosecond Extreme Ultraviolet Reflection-Absorption Spectroscopy.
AB  - Understanding the chemical nature of defect sites as well as the mechanism of
      defect-mediated recombination is critical for the rational design of energy
      conversion materials with improved efficiency. Using femtosecond extreme
      ultraviolet (XUV) spectroscopy in conjunction with X-ray photoelectron
      spectroscopy (XPS), we present results on the ultrafast electron dynamics in NiO
      prepared with varying concentrations of defect states. We find that oxygen
      vacancy defects do not serve as the primary recombination center, but rather the
      recombination rate scales linearly with the density of Ni metal defects. This
      suggests that grain boundaries between Ni metal and NiO are responsible for fast
      carrier recombination in partially reduced NiO. Our kinetic model shows that the
      photoexcited electrons self-trap via small polaron formation on the subpicosecond
      time scale. Additionally, we estimate an absolute measurement of small polaron
      formation rates, direct versus defect-mediated recombination rates, and the small
      polaron diffusion coefficient in NiO. This study provides important parameters
      for engineering NiO based materials for solar energy harvesting applications.

PMID- 30091929
TI  - Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles
      via Indole Intermediates.
AB  - The previously unexplored Grignard addition to oxindoles provides a regiospecific
      approach to 2- and 2,3-disubstituted indole derivatives in high yields via a one
      pot aromatization driven dehydration pathway. This method allows a convenient
      preparation of diallyl indoles that are used as ring-closing metathesis (RCM)
      precursors for the orthogonal synthesis of pyrido[1,2- a]indoles and carbazoles.
      The synthetic utility of this method is illustrated by the synthesis of a
      microtubulin inhibitor and naturally occurring carbazole alkaloids.

PMID- 30091930
TI  - Enantioselective Synthesis of ABCF Tetracyclic Framework of Daphniphyllum
      Alkaloid Calyciphylline N.
AB  - Efforts toward the enantioselective synthesis of Daphniphyllum alkaloid
      calyciphylline N which leads to efficient preparation of the ABCF tetracyclic
      framework containing three bridgehead all-carbon quaternary stereocenters are
      described. This synthetic work features the utilization of an asymmetric
      conjugate addition to install the C5 all-carbon quaternary center, an efficient
      successive inter/intramolecular aldol sequence to build the critical
      bicyclo[2.2.2]octanone BC core, and a ring closing metathesis reaction followed
      by stereoselective Nagata conjugate cyanation to deliver the functionalized F
      ring.

PMID- 30091931
TI  - Copper-Catalyzed Intermolecular Reductive Radical Difluoroalkylation-Thiolation
      of Aryl Alkenes.
AB  - A novel radical-involved alkene difunctionalization catalyzed by the
      copper/B2pin2 system has been developed, leading to the difluoroalkylation
      thiolation of aryl alkenes. The use of B2pin2 as an organic reductant enables the
      simultaneous installation of a C(sp3)-C(F2R) bond and a C(sp3)-S(R) bond across
      the C?C bond of aryl alkenes by utilizing two electrophilic reactants. The
      reaction exhibits broad substrate scope, excellent diastereoselectivity, and
      moderate to good yields. Moreover, the reaction can be conducted on a gram scale
      with good yield achieved.

PMID- 30091932
TI  - Visible-Light-Induced Intramolecular C(sp2)-H Amination and Aziridination of
      Azidoformates via a Triplet Nitrene Pathway.
AB  - Catalytic intramolecular C-H amination and aziridination reactions of o
      allylphenyl azidoformates have been achieved under visible-light irradiation,
      providing a mild, clean, and efficient method for the synthesis of useful
      benzoxazolones and [5.1.0] bicyclic aziridines. Mechanistic studies suggest that
      a triplet nitrene acts as the reactive intermediate. The chemoselectivity of the
      reaction, with alkyl olefin aziridination ? electron deficient olefin
      aziridination ~ C(sp2)-H amination ? C(sp3)-H amination was observed, which may
      be instructive in the development of an understanding of visible-light-induced
      triplet nitrene transformation reactions.

PMID- 30091933
TI  - Self-Assembly-Directed Cancer Cell Membrane Insertion of Synthetic Analogues for
      Permeability Alteration.
AB  - Inspired by the metamorphosis of pore-forming toxins from soluble inactive
      monomers to cytolytic transmembrane assemblies, we developed self-assembly
      directed membrane insertion of synthetic analogues for permeability alteration.
      An expanded pi-conjugation-based molecular precursor with an extremely high
      rigidity and a long hydrophobic length that is comparable to the hydrophobic
      width of plasma membrane was synthesized for membrane-inserted self-assembly.
      Guided by the cancer biomarker expression in vitro, the soluble precursors
      transform into hydrophobic monomers  forming assemblies inserted into the fluid
      phase of the membrane exclusively. Membrane insertion of rigid synthetic
      analogues destroys the selective permeability of the plasma membrane gradually.
      It eventually leads to cancer cell death, including drug resistant cancer cells.

PMID- 30091934
TI  - Efficient Propulsion and Hovering of Bubble-Driven Hollow Micromotors underneath
      an Air-Liquid Interface.
AB  - Bubble-driven micromotors have attracted substantial interest due to their
      remarkable self-motile and cargo-delivering abilities in biomedical or
      environmental applications. Here, we developed a hollow micromotor that
      experiences fast self-propulsion underneath an air-liquid interface by periodic
      bubble growth and collapse. The collapsing of a single microbubble induces a ~1
      m.s-1 impulsive jetting flow that instantaneously pushes the micromotor forward.
      Unlike previously reported micromotors propelled by the recoiling of bubbles,
      cavitation-induced jetting further utilizes the energy stored in the bubble to
      propel the micromotor and thus enhances the energy conversion efficiency by 3
      orders of magnitude. Four different modes of propulsion are, for the first time,
      identified by quantifying the dependence of propulsion strength on microbubble
      size. Meanwhile, the vertical component of the jetting flow counteracts the
      buoyancy of the micromotor-bubble dimer and facilitates counterintuitive hovering
      underneath the air-liquid interface. This work not only enriches the
      understanding of the propulsion mechanism of bubble-driven micromotors but also
      gives insight into the physical aspects of cavitation bubble dynamics near the
      air-liquid interface on the microscale.

PMID- 30091935
TI  - Rh(III)-Catalyzed Synthesis of 2-Alkylbenzimidazoles from Imidamides and N
      Hydroxycarbamates.
AB  - An efficient tandem reaction of imidamides and N-hydroxycarbamates has been
      developed. Valuable 2-alkylbenzimidazoles could be easily obtained in up to 97%
      yield for more than 20 examples. The products would further streamline the
      synthesis of molecules, which are essential building blocks in organic synthesis
      and drug discovery. This protocol features high regioselectivity, efficiency,
      good tolerance of functional groups, and mild reaction conditions.

PMID- 30091936
TI  - Synthesis of Enantioenriched alpha,alpha-Dichloro- and alpha,alpha-Difluoro-beta
      Hydroxy Esters and Amides by Ruthenium-Catalyzed Asymmetric Transfer
      Hydrogenation.
AB  - A mild and convenient approach was developed to prepare a series of alpha,alpha
      dihalogeno beta-hydroxy esters or amides by using commercially available Noyori's
      complex [RuCl( p-cymene)( R, R)-TsDPEN] as a catalyst (S/C = 100-200) in the
      asymmetric transfer hydrogenation of the corresponding ketones. Moderate to high
      yields (up to 99%) and excellent enantioselectivities (up to >99% ee) were
      achieved for a series of variously substituted dichloro and difluoro beta-hydroxy
      esters and amides.

PMID- 30091937
TI  - Age-Dependent Patellofemoral Pain: Hip and Knee Risk Landing Profiles in
      Prepubescent and Postpubescent Female Athletes.
AB  - BACKGROUND: Female athletes are at an increased risk of developing patellofemoral
      pain (PFP) relative to male athletes. The unique effects of maturation may
      compound that risk. Hypothesis/Purpose: The purpose was to evaluate the
      neuromuscular control mechanisms that are adaptive to pubertal maturation and
      determine their relative contribution to PFP development. It was hypothesized
      that aberrant landing mechanics (reduced sagittal-plane and increased frontal-
      and transverse-plane kinematics and kinetics) would be associated with an
      increased risk for PFP. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: There were 506 high school female athletes who completed a detailed
      medical history, the Anterior Knee Pain Scale, and a knee examination for the
      diagnosis of PFP and attended follow-up appointments. Athletes performed a drop
      vertical jump task instrumented with force plates, and biomechanical measures
      generated from standard 3-dimensional biomechanical analyses were used to
      classify participants into high- or low-risk knee and hip landing profiles for
      the development of PFP. The biomechanical measures used in the knee landing
      profile included sagittal-plane knee range of motion, peak knee abduction angle,
      peak knee abduction moment, and peak-to-peak transverse-plane knee moment. The
      biomechanical measures used in the hip landing profile included sagittal-plane
      hip range of motion, peak hip extensor moment, peak abductor moment, and peak hip
      rotator moment. Testing was conducted at sport-specific preseason appointments
      over the course of 2 years, and changes in pubertal status, landing profile, and
      PFP development were documented. RESULTS: Female athletes with high-risk hip
      landing profiles experienced increased hip flexion and decreased abductor,
      rotator, and extensor moments. Participants with high-risk hip landing profiles
      who transitioned to postpubertal status at follow-up had higher odds (odds ratio,
      2.1 [95% CI, 1.1-4.0]; P = .02) of moving to a low-risk hip landing profile
      compared with those who had not reached postpubertal status at follow-up.
      Participants with high-risk knee landing profiles experienced decreased knee
      flexion and increased knee abduction, external abductor, and external rotator
      moments. Pubertal maturation was not associated with a change in the high-risk
      knee landing profile at follow-up. CONCLUSION: The progression from prepubertal
      to postpubertal status may have a protective effect on high-risk hip mechanics
      but no similar adaptations in high-risk knee mechanics during maturation. These
      data indicate that before puberty, maladaptive hip mechanics may contribute to
      PFP, while aberrant knee mechanics associated with PFP are sustained throughout
      the maturational process in young female athletes.

PMID- 30091938
TI  - Inaccuracy of asthma-related self-reported health-care utilization data compared
      to Medicaid claims.

PMID- 30091939
TI  - Spinal Motion Restriction in the Trauma Patient - A Joint Position Statement.
AB  - The American College of Surgeons Committee on Trauma (ACS-COT), American College
      of Emergency Physicians (ACEP), and the National Association of EMS Physicians
      (NAEMSP) have previously offered varied guidance on the role of backboards and
      spinal immobilization in out-of-hospital situations. This updated consensus
      statement on spinal motion restriction in the trauma patient represents the
      collective positions of the ACS-COT, ACEP and NAEMSP. It has further been
      formally endorsed by a number of national stakeholder organizations. This updated
      uniform guidance is intended for use by emergency medical services (EMS)
      personnel, EMS medical directors, emergency physicians, trauma surgeons, and
      nurses as they strive to improve the care of trauma victims within their
      respective domains.

PMID- 30091941
TI  - CUSTOM-MADE TITANIUM MESH FOR MAXILLARY BONE AUGMENTATION WITH IMMEDIATE IMPLANTS
      AND DELAYED LOADING.
AB  - No abstract is required for clinical case letters.

PMID- 30091942
TI  - Strengthening the Effectiveness of National, State, and Local Efforts to Improve
      HPV Vaccination Coverage in the United States: Recommendations From the National
      Vaccine Advisory Committee.
AB  - In February 2018, recognizing the suboptimal rates of human papillomavirus (HPV)
      vaccination in the United States, the assistant secretary for health of the US
      Department of Health and Human Services charged the National Vaccine Advisory
      Committee (NVAC) with providing recommendations on how to strengthen the
      effectiveness of national, state, and local efforts to improve HPV vaccination
      coverage rates. In the same month, the NVAC established the HPV Vaccination
      Implementation Working Group and assigned it to develop these recommendations.
      The working group sought advice from federal and nonfederal partners. This NVAC
      report recommends ways to improve HPV vaccination coverage rates by focusing on 4
      areas of activity: (1) identifying additional national partners, (2) guiding
      coalition building for states, (3) engaging integrated health care delivery
      networks, and (4) addressing provider needs in rural areas.

PMID- 30091943
TI  - Oncological and genetic factors impacting PDX model construction with NSG mice in
      pancreatic cancer.
AB  - A patient-derived xenograft (PDX) approach, which relies on direct
      transplantation of tumor specimens into an immunocompromised animal, is a
      commonly used method for investigating tumor therapy predictions in vivo. This
      study evaluated influencing factors, including clinical, oncological, and genetic
      variables, for a pancreatic PDX model in mice. Tumor specimens were obtained from
      121 patients with pancreatic ductal adenocarcinoma who underwent surgical
      resection at the Changhai Pancreatic Surgery Medical Center (Shanghai, China)
      between April 2016 and February 2017. Pancreatic cancer (PC) samples <3 mm3 were
      subcutaneously implanted into the NOD/Shi-scid/IL-2Rgammanull (NSG) mice. Once
      the xenograft reached 300-500 mm3 or reached 180 d after cell inoculation, the
      tumor was excised. Part of the tumor was subsequently transplanted to next
      generation mice, and another part was analyzed by using immunohistochemistry.
      Among the 121 patients with PC, tumor xenograft was successfully generated in 86
      patients (71.1%). Primary tumor >3.5 cm in size was independently associated with
      xenograft formation rate. In addition, several enriched mutated genes within the
      VEGF pathway and higher microvessel density were found in the positive group
      (with xenograft) compared with the negative group (without xenograft). We
      concluded that tumor size and mutated VEGF pathway in PC are important factors
      affecting PDX model construction with NSG mice.-Guo, S., Gao, S., Liu, R., Shen,
      J., Shi, X., Bai, S., Wang, H., Zheng, K., Shao, Z., Liang, C., Peng, S., Jin, G.
      Oncological and genetic factors impacting PDX model construction with NSG mice in
      pancreatic cancer.

PMID- 30091944
TI  - Molecularly Confirmed Acute, Fatal Sarcocystis falcatula Infection in the Rainbow
      Lorikeets (Trichoglossus moluccanus) at the Philadelphia Zoo.
AB  - The protozoan parasite Sarcocystis falcatula is an important cause of clinical
      disease in several avian intermediate hosts. The host range of S. falcatula is
      wide and numerous outbreaks of acute sarcocystosis have been reported in
      passerine and psittacine birds in captivity in the Americas. Previous diagnosis
      was performed by serologic methods, light and/or electron microscopic
      examinations with limited molecular confirmation. Here, we report histological
      and molecular diagnosis of acute, fatal S. falcatula infections in rainbow
      lorikeets (Trichoglossus moluccanus) at the Philadelphia Zoo. Pulmonary
      sarcocystosis was suspected antemortem in 3 lorikeets (3-5 yr old); these birds
      died despite anti-protozoal therapy. The predominant lesion was pneumonia
      associated with S. falcatula-like schizonts in pulmonary vascular endothelium.
      The multilocus PCR-DNA sequencing (18S rDNA, 28S rDNA, ITS-1, and cox1) of frozen
      lung tissue confirmed S. falcatula infections in all 3 birds. Our results and
      previous studies suggest that acute pulmonary form of sarcocystosis is a major
      contributor of death to old world psittacine birds.

PMID- 30091947
TI  - Predicting Sagittal Plane Lifting Postures From Image Bounding Box Dimensions.
AB  - OBJECTIVE: A method for automatically classifying lifting postures from simple
      features in video recordings was developed and tested. We explored if an
      "elastic" rectangular bounding box, drawn tightly around the subject, can be used
      for classifying standing, stooping, and squatting at the lift origin and
      destination. BACKGROUND: Current marker-less video tracking methods depend on a
      priori skeletal human models, which are prone to error from poor illumination,
      obstructions, and difficulty placing cameras in the field. Robust computer vision
      algorithms based on spatiotemporal features were previously applied for
      evaluating repetitive motion tasks, exertion frequency, and duty cycle. METHODS:
      Mannequin poses were systematically generated using the Michigan 3DSSPP software
      for a wide range of hand locations and lifting postures. The stature-normalized
      height and width of a bounding box were measured in the sagittal plane and when
      rotated horizontally by 30 degrees . After randomly ordering the data, a
      classification and regression tree algorithm was trained to classify the lifting
      postures. RESULTS: The resulting tree had four levels and four splits,
      misclassifying 0.36% training-set cases. The algorithm was tested using 30 video
      clips of industrial lifting tasks, misclassifying 3.33% test-set cases. The
      sensitivity and specificity, respectively, were 100.0% and 100.0% for squatting,
      90.0% and 100.0% for stooping, and 100.0% and 95.0% for standing. CONCLUSIONS:
      The tree classification algorithm is capable of classifying lifting postures
      based only on dimensions of bounding boxes. APPLICATIONS: It is anticipated that
      this practical algorithm can be implemented on handheld devices such as a
      smartphone, making it readily accessible to practitioners.

PMID- 30091946
TI  - Attainment of Functional and Social Independence in Adult Survivors of Pediatric
      CNS Tumors: A Report From the St Jude Lifetime Cohort Study.
AB  - Purpose Beyond survival, achieving independence is a primary goal for adult
      survivors of pediatric CNS tumors. However, the prevalence of and risk factors
      for failure to achieve independence, assessed with multiple concurrent
      indicators, have not been examined. Patients and Methods Functional and social
      independence was assessed in 306 survivors (astrocytoma [n = 130],
      medulloblastoma [n = 77], ependymoma [n = 36], and other [n = 63]; median current
      age, 25.3 years [range, 18.9 to 53.1 years]; time since diagnosis, 16.8 years
      [range, 10.6 to 41.8 years]). Six observed indicators were used to identify
      latent classes of independence, which included employment, living independently,
      assistance with personal care, assistance with routine needs, obtaining a
      driver's license, and marital status. Physical performance impairments were
      defined as scores < 10th percentile on measures of aerobic capacity, strength,
      flexibility, balance, mobility, and adaptive function. Multinomial logistic
      regression estimated odds ratios (ORs) and 95% CIs were calculated for
      associations of disease/treatment exposures and impairments in physical
      performance with nonindependence. Results Three classes of independence were
      identified as independent (40%), moderately independent (34%), and nonindependent
      (26%). In multivariable models, craniospinal irradiation (OR, 4.20; 95% CI, 1.69
      to 10.44) and younger age at diagnosis (OR, 1.24; 95% CI, 1.14 to 1.35) were
      associated with risk of nonindependence versus independence. Beyond impaired IQ,
      limitations in aerobic capacity (OR, 5.47; 95% CI, 1.78 to 16.76), flexibility
      (OR, 3.66; 95% CI, 1.11 to 12.03), and adaptive physical function (OR, 11.54; 95%
      CI, 3.57 to 37.27) were associated with nonindependence versus independence.
      Nonindependent survivors reported reduced physical but not mental health-related
      quality of life compared with independent survivors. Conclusion Sixty percent of
      survivors of pediatric CNS tumors do not achieve complete independence as adults.
      Reduction in intensity of primary therapies and interventions that target
      physical performance and adaptive deficits may help survivors to achieve greater
      independence.

PMID- 30091945
TI  - Addition of Vincristine and Irinotecan to Vincristine, Dactinomycin, and
      Cyclophosphamide Does Not Improve Outcome for Intermediate-Risk Rhabdomyosarcoma:
      A Report From the Children's Oncology Group.
AB  - Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either
      nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site
      or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to
      improve the outcome of patients with intermediate-risk RMS by substituting
      vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and
      cyclophosphamide (VAC) courses. All patients received a lower dose of
      cyclophosphamide and earlier radiation therapy than in previous trials. Patients
      and Methods Patients were randomly assigned at study entry to either VAC
      (cumulative cyclophosphamide dose, 16.8 g/m2) or VAC/VI (cumulative
      cyclophosphamide dose, 8.4 g/m2) for 42 weeks of therapy. Radiation therapy
      started at week 4, with individualized local control plans permitted for patients
      younger than 24 months. The primary study end point was event-free survival
      (EFS). The study design had an 80% power (5% one-sided alpha-level) to detect an
      improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total
      of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8
      years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year
      overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS
      and ERMS subgroups, no difference in outcome by treatment arm was found. Severe
      hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition
      of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS.
      VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide
      dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.

PMID- 30091948
TI  - Extremely low high-density-lipoprotein cholesterol due to an unusual non
      inherited cause: a case report.

PMID- 30091949
TI  - Screening of the immunomodulatory and antibacterial activity of Termitomyces
      letestui (Pat.) Heim (Lyophyllaceae), an edible mushroom from Cameroon.
AB  - Background Globally, Termitomyces letestui is used by different communities to
      treat various illnesses, including bacterial infection, although with limited
      scientific evidence. The current study aims to assess the immunomodulatory and
      antibacterial properties of the water extract of a wild mushroom, T. letestui in
      mice model. Methods The base study was completed following the standard methods
      and procedures using white mice Mus musculus. The immunomodulatory was
      investigated for humoral and cell-mediated response in both the normal and
      dexamethasone-immunosuppressed mice. An immunostimulatory drug, levamisole, was
      used as reference. The treatment was done daily and the extract doses of 250 and
      500 mg/kg bwt were used. Delayed-type hypersensitivity reaction (DTH), mice
      lethality rate and hemagglutination antibody titer were determined. Disc
      diffusion assay was performed using the Muller-Hinton agar to assess the effect
      against Escherichia coli and Staphylococcus aureus. The statistical analysis was
      performed using GraphPad prism 5.0 a Software. Results T. letestui water extract
      (TLAE) provided significant inhibition zones against E. coli and S. aureus.
      TLAE=, along with the antigen (Salmonella typhi) showed a significant increase in
      the circulating antibody titer and reduced the lethality rate in mice. The
      extract also showed significant increase in the DTH response against S. typhi.
      Conclusions This preliminary study demonstrated that TLAE caused a significant
      immunostimulatory effect on both the cell-mediated and humoral immune systems in
      the mice and antibacterial property against E. coli and S. aureus.

PMID- 30091951
TI  - Acta Reumatologica Portuguesa: the future is digital.

PMID- 30091950
TI  - Does the risk of arterial hypertension increase in the course of triptorelin
      treatment?
AB  - BACKGROUND: Gonadotropin-releasing hormone agonists (GnRH-a) are common treatment
      options for central precocious puberty (CPP) in childhood. GnRH-a treatment is
      useful and has a good safety profile, with minimal adverse effects and no severe
      long-term consequences. The common side effects in children are menopause-like
      symptoms and local adverse events at the injection site. CASE PRESENTATION: We
      present the case of a girl with CPP who developed arterial hypertension from
      treatment with GnRH-a (triptorelin). Comprehensive diagnostic studies ruled out
      other causes for her hypertension and its complications. After therapy was
      interrupted, her blood pressure remained within normal limits for age.
      Consequently, we hypothesize that the hypertension presented by our patient was
      related to triptorelin treatment. CONCLUSIONS: Although the etiology of this
      adverse event is not known and only some hypotheses can be made, clinicians
      should be aware that arterial hypertension might appear during triptorelin
      treatment in childhood with CPP. Therefore, they should routinely monitor the
      arterial blood pressure of patients under treatment.

PMID- 30091952
TI  - The GO-DACT protocol: a multicentre, randomized, double-blind, parallel-group
      study to compare the efficacy of golimumab in combination with methotrexate (MTX)
      versus MTX monotherapy.
AB  - The GO-DACT is an investigator-initiated, national, multicentric randomized
      placebo-controlled double-blinded trial, that assesses dactylitis as primary
      endpoint. Psoriatic arthritis patients naive to methotrexate and biologic disease
      modifying anti-rheumatic drugs, with at least one active dactylitis, were
      assigned to golimumab in combination with methotrexate or placebo in combination
      with methotrexate, for 24 weeks. Both clinical (dactylitis severity score and the
      Leeds dactylitis index) and imaging (high resolution magnetic resonance imaging),
      among others, were assessed as outcomes. The main objective of GO-DACT is to
      provide evidence to improve the treatment algorithm and care of psoriatic
      arthritis patients with active dactylitis. In this manuscript we describe the GO
      DACT protocol and general concepts of the methodology of this trial.

PMID- 30091953
TI  - Adherence to the recommended prevention strategies before and after a hip
      fragility fracture: what makes us go blind?
AB  - OBJECTIVES: Our main objective was to evaluate the percentage of patients under
      anti-osteoporotic treatment (OT) at the time of hip fracture (HF) and one and
      four years after the HF event. We compared these results with the percentage of
      patients who should be under treatment at all three stages, according to the
      recently published Portuguese cost-effectiveness recommendations (PCER) for OT.
      Data regarding occurrence of new fragility fractures and mortality were also
      determined, one and four years after the HF event. Our secondary objective was to
      evaluate characteristics of patients associated with OT at the time of hip
      fracture.. MATERIAL AND METHODS: Patients hospitalized due to HF between May 1st
      and October 31st of 2013 in a single tertiary hospital, were selected for this
      study. Data regarding demographic, clinical features (including the clinical risk
      factors for fracture considered by FRAX(r)), level of independence in daily
      activities (Katz index), comorbidity (Charlson index) and OT were recorded at the
      time of the HF. The subsequent risk of fracture was estimated for each patient
      with FRAX(r) (without mineral bone density). Mortality and the percentage of
      patients receiving an OT prescription and suffering a new osteoporotic fracture,
      at one and four years after the HF event, were established. RESULTS: One hundred
      and thirty patients were included, with a mean age of 81.6+/-8.6 years. At the
      time of the HF only 28(21.5%) of the patients were receiving some form of OT.
      According to PCER, 115(88.5%) of these patients should be undergoing treatment
      according to FRAX(r) estimated risk, 30(23.1%) based on previous fractures and
      119(91.5%) based on either criteria. The score of comorbidities was negatively
      associated with the prescription of OT at baseline (OR=0.17 [0.05-0.53], p=0.011)
      while the level of independence in daily activities was associated with higher
      probability of being treated (OR=3.20 [1.30-7.89], p=0.003). At one year after
      the HF, 39/130(30%) of patients had died. Although, according to PCER, all the
      remaining patients should be under OT based on the history of HF, only
      11/91(12.1%) had received an OT prescription and 5/91(5.5%) suffered a new
      osteoporotic fracture during this period. At four years after the HF, 65/130
      (50%) of patients had died. Only 6 of the remaining 65 (9.2%) were receiving an
      OT prescription and 9/65(13.8%) had suffered an additional fractured.
      CONCLUSIONS: Similar to other countries, the percentage of patients receiving OT
      at the time and especially after a HF is extremely low. Risk estimations with
      FRAX(r) and application of current PCER should allow clinicians to introduce
      appropriate primary and secondary preventive measures. Comorbidities and
      dependence seem to be important reasons for this undertreatment.

PMID- 30091954
TI  - Cross-cultural adaptation and validation of the Portuguese version of the Oxford
      Shoulder Score (OSS).
AB  - OBJECTIVE: To translate and culturally adapt the Oxford Shoulder Score (OSS) to
      the European Portuguese language, and to test its reliability (internal
      consistency, reproducibility and measurement error) and validity (construct
      validity). METHODS: The OSS Portuguese version was obtained through translations,
      back-translations, consensus panels, clinical review and cognitive pre-test.
      Portuguese OSS, Disabilities of the Arm, Shoulder and Hand (DASH) questionnaires,
      and the visual analogue scales of pain at rest [VAS rest] and during movement
      [VAS movement] were applied to 111 subjects with shoulder pain (degenerative or
      inflammatory disorders) and recommended for physical therapy. A clinical and
      sociodemographic questionnaire was also applied. RESULTS: The reliability was
      good, with a Cronbach's alpha coefficient of 0.90, an intraclass correlation
      coefficient (ICC) of 0.92, a standard error of measurement (SEM) of 2.59 points
      and a smallest detectable change (SDC) of 7.18 points. Construct validity was
      supported by the confirmation of three initial hypotheses involving expected
      significant correlation between OSS and other measures (DASH, VAS rest and VAS
      movement) and between OSS and the number of days of work absenteeism. CONCLUSION:
      The Portuguese OSS version presented suitable psychometric properties, in terms
      of reliability (internal consistency, reproducibility and measurement error) and
      validity (construct validity).

PMID- 30091955
TI  - Identification of Key Genes and Pathways in Rheumatoid Arthritis Gene Expression
      Profile by Bioinformatics.
AB  - OBJECTIVE: The aim of this study was to identify potential key candidate genes
      and uncover their potential mechanisms in rheumatoid arthritis. MATERIALS AND
      METHODS: The gene expression profiles of GSE12021, GSE55457, GSE55584 and
      GSE55235 were downloaded from the gene expression omnibus database, including 45
      rheumatoid arthritis and 29 normal samples. The differentially expressed genes
      between the two types of samples were identified with the Linear Models for
      Microarray Analysis package using R language. The gene ontology functional and
      pathway enrichment analyses of differentially-expressed genes were performed
      using the database for annotation, visualization and integrated discovery
      software followed by the construction of a protein-protein interaction network.
      In addition, hub gene identification and gene ontology functional and pathway
      enrichment analyses of the modules were performed. RESULTS: The differentially
      expressed genes were mainly involved in immune response, inflammatory response,
      chemokine-mediated signaling pathway for rheumatoid arthritis patients. The top
      hub genes such as interleukin 6, jun proto-oncogene, chemokine receptor 5,
      epidermal growth factor receptor, were identified from the protein-protein
      interaction network. Sub-networks revealed hub genes were involved in significant
      pathways, including chemokine signaling pathway, cytokine-cytokine receptor
      interaction, tumor necrosis factor signaling pathway. The seed node gene is toll
      like receptor 7 and growth arrest and deoxyribonucleic-acid -damage-inducible
      beta in the model-1 and model-2 by module analysis, respectively. CONCLUSION:
      These hub genes may be used as potential targets for rheumatoid arthritis
      diagnosis and treatment.

PMID- 30091956
TI  - Cultural adaptation of the Rheumatoid Arthritis Quality of Life (RAQoL) for
      Portugal.
AB  - BACKGROUND: Rheumatoid Arthritis (RA) is a chronic inflammatory disease that has
      a major impact on patients' quality of life. The Rheumatoid Arthritis Quality of
      Life (RAQoL) questionnaire is a patient-reported outcome measure, specific to RA.
      The aim of this study was to translate and perform the cross-cultural adaptation
      of the RAQoL into Portuguese. MATERIAL AND METHODS: The dual panel methodology
      was used to translate the UK RAQoL into Portuguese. This involved conducting a
      bilingual panel (providing the initial translation into Portuguese) followed by a
      lay panel (where items are assessed for comprehension and acceptability).
      Cognitive debriefing interviews were conducted with Portuguese RA patients to
      determine the face and content validity of the translated scale. RESULTS: The
      translation panels produced a Portuguese version of the RAQoL that was easily
      understood and considered natural by native speakers. Twelve RA patients
      participated in the cognitive debriefing interviews. Patients considered the
      translated questionnaire to be clear, relevant and appropriate. CONCLUSION: The
      Portuguese version of the RAQoL was found to be comprehensible and demonstrated
      excellent face and content validity. Research examining the psychometric
      properties of this Portuguese version of the RAQoL is underway.

PMID- 30091957
TI  - Validation of Oral Health Impact Profile-14 and its association with Hypossialia
      in a Sjogren Syndrome Portuguese Population.
AB  - AIMS: The objective of this study was to perform the Portuguese transcultural
      adaptation of the original Brazilian version of the Oral Health Impact Profile-14
      (OHIP-14) while evaluating the association between hyposalivation and quality of
      life in a Sjogren's Syndrome population. METHODS: The original Brazilian version
      of the Oral Health Impact Profile-14 was culturally adapted following the
      guidelines for cross-cultural adaptation of health-related quality of life
      measures. The questionnaires were administered by trained and calibrated dental
      doctors to 86 patients with Sjogren's Syndrome. Oral Health Impact Profile-14
      properties were examined including reliability, internal consistency and test
      retest reliability, using Cronbach's alpha, total and inter-item correlation, and
      intra-class correlation coefficients, respectively. Whole saliva secretion rates
      and hyposalivation-related variables were collected and statistically analyzed.
      Spearman's rho correlations were obtained between salivary flows and OHIP -14
      domains and total score. Alpha was set at 0.05. Informed consents and local
      ethical committee clearance were obtained. RESULTS: Each question of the
      questionnaire performed adequately. Cronbach alpha values for the 14 questions
      were 0.89 for both test administrations and were lower if item removed. Scores
      for both questionnaire administration and ICC results presented good to excellent
      reliability with ICC ranging from 84% to 92%. Mean salivary flow rate was 0.05
      (SD: 0.03) ml/min and mean stimulated salivary flow was 0.57 (SD: 0.44) ml/min,
      which are within expected values in a population with hyposalivation. The results
      describe a negative and significant correlation between total OHIP-14-PT score,
      physical pain, physical disability domain and stimulated and differential
      salivary flows. There was a negative and significant correlation between
      unstimulated salivary flow with physical pain. CONCLUSION: Within the limitations
      of this study, the OHIP-14-PT seems to be a valid and reliable instrument for
      measuring oral health related quality of life in patients with Sjogren's
      Syndrome. Both differential and stimulated salivary flows seem to correlate
      negatively with age and the quality of life is significantly diminished by lower
      stimulated salivary flow rates.

PMID- 30091958
TI  - Devic's syndrome and mixed connective tissue disease: an unusual association.
AB  - Devic's disease or neuromyelitis optica (NMO) is an autoimmune, inflammatory and
      demyelinating pathology of the central nervous system that affects the optic
      nerve and the spinal cord. Diagnosis confirmed by imaging, magnetic resonance
      (MR) and the presence of the anti-aquaporin 4 antibody (anti-AQP4). We describe
      two cases of patients with mixed connective tissue disease (MCTD) and Devic's
      disease, who had anti-AQP4 positive and areas with neuroaxis MR abnormalities,
      showing this rare association.

PMID- 30091959
TI  - Intra-articular epithelioid sarcoma of the knee: a diagnostic challenge.
AB  - Epithelioid sarcoma is a rare mesenchymal neoplasm characterized by aggregates of
      epithelioid cells. Intra-articular occurrence is exceedingly rare with only few
      reports described in the literature. A 22 year-old man presented a progressive
      mechanical knee pain. Initially, the investigation revealed a non-infectious
      unspecific synovitis. The patient gradually presented increasing knee enlargement
      and functional impairment. Intra-articular nodular proliferation with bone
      invasion was later observed on magnetic resonance imaging reevaluation. Pigmented
      villonodular synovitis hypothesis was considered. The biopsy ultimately revealed
      nodules of epithelioid cells with an immunoprofile compatible with epithelioid
      sarcoma diagnosis. The patient underwent neoadjuvant chemotherapy and
      radiotherapy and an above-knee amputation was performed.

PMID- 30091960
TI  - Intravenous human immunoglobulin for the treatment of severe longitudinal
      extensive transverse myelitis associated with systemic lupus erythematous.
AB  - A 39-year-old female with systemic lupus erythematous (SLE) presented with fever,
      headaches and rash and was treated with empiric antibiotics for a presumable
      meningitis. However, cerebrospinal fluid turned out to be sterile and fever
      persisted with onset of hyporeflexive paraparesis with sensory loss below D10.
      Magnetic resonance imaging (MRI) demonstrated intradural-extramedullary hematoma
      (related to traumatic lumbar puncture), which was successfully drained.
      Subsequent surgical scar infection occurred and was treated accordingly. Due to
      persistent deficits and urinary retention development, she repeated MRI, which
      showed holocord abnormal T2 hyperintensity. After excluding other causes, SLE
      associated longitudinal extensive transverse myelitis was diagnosed and treated
      with high-dose steroids and intravenous human immunoglobulin (IVIG), with
      reduction in intensity and extension of abnormal T2 signal within only one week.
      Monthly IVIG was kept for 6 months with progressive ability to walk and MRI
      findings resolution in 3 months. Four months after IVIG suspension no recurrence
      occurred.

PMID- 30091961
TI  - My Phenotype speaks: please do not harm me with biopsy needle.
AB  - Fibrodysplasia ossificans progressiva is characterized by congenital skeletal
      anomalies and progressive heterotopic ossification. We present a 4 year old male
      patient who underwent unnecessary harmful multiple biopsies before the diagnosis
      of fibrodysplasia ossificans progressiva is made. Though rare, diagnosis of
      fibrodysplasia ossificans progressiva should be considered whenever
      characteristic radiographic features of multifocal heterotopic bone formation is
      seen along with the valgus deformities of the big toes.

PMID- 30091962
TI  - Safety of Etanercept in the treatment of rheumatic disease patients with
      Hepatitis C virus infection.
AB  - Hepatitis C virus (HCV) infection is a major public health problem. Because
      Tumour Necrosis Factor (TNF) seems to have an important role in immune response
      to HCV infection, suppression by TNFi (TNF inhibitors) may pose a potential
      worsening of chronic HCV infection. We report our experience with 3 cases of
      patients with chronic HCV infection and advanced liver disease, with different
      Rheumatic diseases, treated with a TNFi, etanercept (ETN), for a period ranging
      from 4 months to 4 years without hepatitis C treatment and, in two of them,
      concomitant therapy with direct-acting antiviral agents (DAA) and afterwards.
      Although increasing number of clinical reports support the short-term safety and
      efficacy of TNFi in patients with HCV, some uncertainties remain regarding long
      term. These cases suggests that the risk of HCV reactivation related to TNFi
      remains low even without concomitant antiviral therapy. Nevertheless, a strict
      collaboration between rheumatologists and gastroenterologists/hepatologists. Our
      results also showed a good tolerance and efficacy when used concomitantly the new
      direct-acting antivirals drugs with ETN.

PMID- 30091964
TI  - QuickStats: Age-Adjusted Death Rates* for Motor Vehicle Traffic Injury? - United
      States, 2016.

PMID- 30091963
TI  - Preoperative Assessment of Ultrasonographic Measurement of Antral Area for
      Gastric Content.
AB  - BACKGROUND Pulmonary aspiration of the gastric contents is a serious
      perioperative complication. The aim of this study was to evaluate the efficacy of
      portable ultrasonography in the preoperative evaluation of the gastric contents
      of patients. The secondary aim was to examine the relationship between gastric
      antrum cross-sectional area and age and body mass index (BMI). MATERIAL AND
      METHODS This single-center, prospective, cross-sectional study included 120
      patients who underwent surgery. Measurements the gastric antral cross-sectional
      areas and quantitative and qualitative measurements of the stomach were taken by
      ultrasonography guidance in all patients. RESULTS With the patient in a supine
      position, the mean gastric antrum cross-sectional area was found to be 3.4+/-2.43
      cm2 (range, 0.79-17.3 cm2). As the number of hours of fasting increased, the
      gastric antral cross-sectional area statistically significantly decreased
      (P<0.05). Increased age and BMI values were determined to increase the gastric
      antrum cross-sectional area in a linear correlation; r=0.209, P<0.05 and r=0.252,
      P=0.05, respectively. It was determined that 20.8% of the patients exceeded the
      high-risk stomach antral cutoff cross-sectional area that was defined as 340 mm2
      in patients fasting for at least 8 hours. CONCLUSIONS It was determined that
      bedside ultrasonography is a useful, non-invasive tool in the determination of
      gastric content and volume. A significant proportion of surgical patients may not
      present with an empty stomach despite the recommended fasting protocols.

PMID- 30091965
TI  - Update: Interim Guidance for Preconception Counseling and Prevention of Sexual
      Transmission of Zika Virus for Men with Possible Zika Virus Exposure - United
      States, August 2018.
AB  - Zika virus infection can occur as a result of mosquitoborne or sexual
      transmission of the virus. Infection during pregnancy is a cause of fetal brain
      abnormalities and other serious birth defects (1,2). CDC has updated the interim
      guidance for men with possible Zika virus exposure who 1) are planning to
      conceive with their partner, or 2) want to prevent sexual transmission of Zika
      virus at any time (3). CDC now recommends that men with possible Zika virus
      exposure who are planning to conceive with their partner wait for at least 3
      months after symptom onset (if symptomatic) or their last possible Zika virus
      exposure (if asymptomatic) before engaging in unprotected sex. CDC now also
      recommends that for couples who are not trying to conceive, men can consider
      using condoms or abstaining from sex for at least 3 months after symptom onset
      (if symptomatic) or their last possible Zika virus exposure (if asymptomatic) to
      minimize their risk for sexual transmission of Zika virus. All other guidance for
      Zika virus remains unchanged. The definition of possible Zika virus exposure
      remains unchanged and includes travel to or residence in an area with risk for
      Zika virus transmission (https://wwwnc.cdc.gov/travel/page/world-map-areas-with
      zika) or sex without a condom with a partner who traveled to or lives in an area
      with risk for Zika virus transmission. CDC will continue to update
      recommendations as new information becomes available.

PMID- 30091966
TI  - Naloxone Administration Frequency During Emergency Medical Service Events -
      United States, 2012-2016.
AB  - As the opioid epidemic in the United States has continued since the early 2000s
      (1,2), most descriptions have focused on misuse and deaths. Increased cooperation
      with state and local partners has enabled more rapid and comprehensive
      surveillance of nonfatal opioid overdoses (3).* Naloxone administrations obtained
      from emergency medical services (EMS) patient care records have served as a
      useful proxy for overdose surveillance in individual communities and might be a
      previously unused data source to describe the opioid epidemic, including fatal
      and nonfatal events, on a national level (4-6). Using data from the National
      Emergency Medical Services Information System (NEMSIS),? the trend in rate of EMS
      naloxone administration events from 2012 to 2016 was compared with opioid
      overdose mortality rates from National Vital Statistics System multiple cause-of
      death mortality files. During 2012-2016, the rate of EMS naloxone administration
      events increased 75.1%, from 573.6 to 1004.4 administrations per 100,000 EMS
      events, mirroring the 79.7% increase in opioid overdose mortality from 7.4 deaths
      per 100,000 persons to 13.3. A bimodal age distribution of patients receiving
      naloxone from EMS parallels a similar age distribution of deaths, with persons
      aged 25-34 years and 45-54 years most affected. However, an accurate estimate of
      the complete injury burden of the opioid epidemic requires assessing nonfatal
      overdoses in addition to deaths. Evaluating and monitoring nonfatal overdose
      events via the novel approach of using EMS data might assist in the development
      of timely interventions to address the evolving opioid crisis.

PMID- 30091968
TI  - Extrapulmonary Nontuberculous Mycobacterial Disease Surveillance - Oregon, 2014
      2016.
AB  - Nontuberculous mycobacteria (NTM), ubiquitous in soil and water, usually infect
      immunocompromised persons. However, even healthy persons are susceptible to
      infection through percutaneous inoculation. Although 77% of NTM diseases manifest
      as primarily pulmonary illnesses (1), NTM also infect skin, bones, joints, the
      lymphatic system, and soft tissue. NTM infections can have incubation periods
      that exceed 5 years (2), often require prolonged treatment, and can lead to
      sepsis and death. Extrapulmonary NTM outbreaks have been reported in association
      with contaminated surgical gentian violet (3), nail salon pedicures (4), and
      tattoos received at tattoo parlors (5), although few surveillance data have been
      available for estimating the public health burden of NTM.* On January 1, 2014,
      the Oregon Health Authority designated extrapulmonary NTM disease a reportable
      condition. To characterize extrapulmonary NTM infection, estimate resources
      required for surveillance, and assess the usefulness of surveillance in outbreak
      detection and investigation, 2014-2016 extrapulmonary NTM surveillance data were
      reviewed, and interviews with stakeholders were conducted. During 2014-2016, 134
      extrapulmonary NTM cases (11 per 1 million persons per year) were reported in
      Oregon. The age distribution was bimodal, with highest incidence among persons
      aged <10 years (20 per 1 million persons per year) and persons aged 60-69 years
      (18 per 1 million persons per year). The most frequently reported predisposing
      factors (occurring within 14-70 days of symptom onset) were soil exposure (41/98;
      42%), immunocompromised condition (42/124; 34%), and surgery (32/120; 27%).
      Overall, 43 (33%) patients were hospitalized, 18 (15%) developed sepsis, and one
      (0.7%) died. Surveillance detected or helped to control two outbreaks at low
      cost. Jurisdictions interested in implementing extrapulmonary NTM surveillance
      can use the Council of State and Territorial Epidemiologists (CSTE) standardized
      case definition (6) for extrapulmonary NTM reporting or investigative guidelines
      maintained by the Oregon Health Authority (7).

PMID- 30091967
TI  - Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities
      Possibly Associated with Congenital Zika Virus Infection - U.S. Territories and
      Freely Associated States, 2018.
AB  - INTRODUCTION: Zika virus infection during pregnancy causes serious birth defects
      and might be associated with neurodevelopmental abnormalities in children. Early
      identification of and intervention for neurodevelopmental problems can improve
      cognitive, social, and behavioral functioning. METHODS: Pregnancies with
      laboratory evidence of confirmed or possible Zika virus infection and infants
      resulting from these pregnancies are included in the U.S. Zika Pregnancy and
      Infant Registry (USZPIR) and followed through active surveillance methods. This
      report includes data on children aged >=1 year born in U.S. territories and
      freely associated states. Receipt of reported follow-up care was assessed, and
      data were reviewed to identify Zika-associated birth defects and
      neurodevelopmental abnormalities possibly associated with congenital Zika virus
      infection. RESULTS: Among 1,450 children of mothers with laboratory evidence of
      confirmed or possible Zika virus infection during pregnancy and with reported
      follow-up care, 76% had developmental screening or evaluation, 60% had postnatal
      neuroimaging, 48% had automated auditory brainstem response-based hearing screen
      or evaluation, and 36% had an ophthalmologic evaluation. Among evaluated
      children, 6% had at least one Zika-associated birth defect identified, 9% had at
      least one neurodevelopmental abnormality possibly associated with congenital Zika
      virus infection identified, and 1% had both. CONCLUSION: One in seven evaluated
      children had a Zika-associated birth defect, a neurodevelopmental abnormality
      possibly associated with congenital Zika virus infection, or both reported to the
      USZPIR. Given that most children did not have evidence of all recommended
      evaluations, additional anomalies might not have been identified. Careful
      monitoring and evaluation of children born to mothers with evidence of Zika virus
      infection during pregnancy is essential for ensuring early detection of possible
      disabilities and early referral to intervention services.

PMID- 30091969
TI  - Opioid Use Disorder Documented at Delivery Hospitalization - United States, 1999
      2014.
AB  - Opioid use by pregnant women represents a significant public health concern given
      the association of opioid exposure and adverse maternal and neonatal outcomes,
      including preterm labor, stillbirth, neonatal abstinence syndrome, and maternal
      mortality (1,2). State-level actions are critical to curbing the opioid epidemic
      through programs and policies to reduce use of prescription opioids and illegal
      opioids including heroin and illicitly manufactured fentanyl, both of which
      contribute to the epidemic (3). Hospital discharge data from the 1999-2014
      Healthcare Cost and Utilization Project (HCUP) were analyzed to describe U.S.
      national and state-specific trends in opioid use disorder documented at delivery
      hospitalization. Nationally, the prevalence of opioid use disorder more than
      quadrupled during 1999-2014 (from 1.5 per 1,000 delivery hospitalizations to 6.5;
      p<0.05). Increasing trends over time were observed in all 28 states with
      available data (p<0.05). In 2014, prevalence ranged from 0.7 in the District of
      Columbia (DC) to 48.6 in Vermont. Continued national, state, and provider efforts
      to prevent, monitor, and treat opioid use disorder among reproductive-aged and
      pregnant women are needed. Efforts might include improved access to data in
      Prescription Drug Monitoring Programs, increased substance abuse screening, use
      of medication-assisted therapy, and substance abuse treatment referrals.

PMID- 30091970
TI  - Correction: Limits on reliable information flows through stochastic populations.
AB  - [This corrects the article DOI: 10.1371/journal.pcbi.1006195.].

PMID- 30091971
TI  - The snail Biomphalaria glabrata as a model to interrogate the molecular basis of
      complex human diseases.

PMID- 30091973
TI  - [STERNAL CLEFT - REPORT OF THREE CASES].
AB  - During the last 25 years we surgically treated three patients with sternal cleft
      anomaly, aged from 6 weeks to 2 years. The aim of this case series is to present
      this extremely rare congenital anomaly and differences in the operative treatment
      of sternal cleft (SC) depending on patients age due to flexibility of the chest
      wall. Patients presented to us with signs of sternal cleft; displaced
      sternoclavicular articulations and paradoxical motion of the skin over the
      defect. Preoperatively we performed X-ray and computed tomography of the chest
      which revealed displaced sternoclavicular articulations with superior incomplete
      sternal cleft and echocardiography which showed orthotopic heart without
      malformations of the great vessels. Surgical treatment included primary closure
      in two infants and Sabiston's technique in a two-year-old girl. All three
      patients were successfully operated without complications.

PMID- 30091972
TI  - Single-strand annealing between inverted DNA repeats: Pathway choice,
      participating proteins, and genome destabilizing consequences.
AB  - Double strand DNA breaks (DSBs) are dangerous events that can result from various
      causes including environmental assaults or the collapse of DNA replication. While
      the efficient and precise repair of DSBs is essential for cell survival, faulty
      repair can lead to genetic instability, making the choice of DSB repair an
      important step. Here we report that inverted DNA repeats (IRs) placed near a DSB
      can channel its repair from an accurate pathway that leads to gene conversion to
      instead a break-induced replication (BIR) pathway that leads to genetic
      instabilities. The effect of IRs is explained by their ability to form unusual
      DNA structures when present in ssDNA that is formed by DSB resection. We
      demonstrate that IRs can form two types of unusual DNA structures, and the choice
      between these structures depends on the length of the spacer separating IRs. In
      particular, IRs separated by a long (1-kb) spacer are predominantly involved in
      inter-molecular single-strand annealing (SSA) leading to the formation of
      inverted dimers; IRs separated by a short (12-bp) spacer participate in intra
      molecular SSA, leading to the formation of fold-back (FB) structures. Both of
      these structures interfere with an accurate DSB repair by gene conversion and
      channel DSB repair into BIR, which promotes genomic destabilization. We also
      report that different protein complexes participate in the processing of FBs
      containing short (12-bp) versus long (1-kb) ssDNA loops. Specifically, FBs with
      short loops are processed by the MRX-Sae2 complex, whereas the Rad1-Rad10 complex
      is responsible for the processing of long loops. Overall, our studies uncover the
      mechanisms of genomic destabilization resulting from re-routing DSB repair into
      unusual pathways by IRs. Given the high abundance of IRs in the human genome, our
      findings may contribute to the understanding of IR-mediated genomic
      destabilization associated with human disease.

PMID- 30091974
TI  - A ZIP1 separation-of-function allele reveals that centromere pairing drives
      meiotic segregation of achiasmate chromosomes in budding yeast.
AB  - In meiosis I, homologous chromosomes segregate away from each other-the first of
      two rounds of chromosome segregation that allow the formation of haploid gametes.
      In prophase I, homologous partners become joined along their length by the
      synaptonemal complex (SC) and crossovers form between the homologs to generate
      links called chiasmata. The chiasmata allow the homologs to act as a single unit,
      called a bivalent, as the chromosomes attach to the microtubules that will
      ultimately pull them away from each other at anaphase I. Recent studies, in
      several organisms, have shown that when the SC disassembles at the end of
      prophase, residual SC proteins remain at the homologous centromeres providing an
      additional link between the homologs. In budding yeast, this centromere pairing
      is correlated with improved segregation of the paired partners in anaphase.
      However, the causal relationship of prophase centromere pairing and subsequent
      disjunction in anaphase has been difficult to demonstrate as has been the
      relationship between SC assembly and the assembly of the centromere pairing
      apparatus. Here, a series of in-frame deletion mutants of the SC component Zip1
      were used to address these questions. The identification of a separation-of
      function allele that disrupts centromere pairing, but not SC assembly, has made
      it possible to demonstrate that centromere pairing and SC assembly have
      mechanistically distinct features and that the centromere pairing function of
      Zip1 drives disjunction of the paired partners in anaphase I.

PMID- 30091975
TI  - Flexible resonance in prefrontal networks with strong feedback inhibition.
AB  - Oscillations are ubiquitous features of brain dynamics that undergo task-related
      changes in synchrony, power, and frequency. The impact of those changes on target
      networks is poorly understood. In this work, we used a biophysically detailed
      model of prefrontal cortex (PFC) to explore the effects of varying the spike
      rate, synchrony, and waveform of strong oscillatory inputs on the behavior of
      cortical networks driven by them. Interacting populations of excitatory and
      inhibitory neurons with strong feedback inhibition are inhibition-based network
      oscillators that exhibit resonance (i.e., larger responses to preferred input
      frequencies). We quantified network responses in terms of mean firing rates and
      the population frequency of network oscillation; and characterized their behavior
      in terms of the natural response to asynchronous input and the resonant response
      to oscillatory inputs. We show that strong feedback inhibition causes the PFC to
      generate internal (natural) oscillations in the beta/gamma frequency range (>15
      Hz) and to maximize principal cell spiking in response to external oscillations
      at slightly higher frequencies. Importantly, we found that the fastest
      oscillation frequency that can be relayed by the network maximizes local
      inhibition and is equal to a frequency even higher than that which maximizes the
      firing rate of excitatory cells; we call this phenomenon population frequency
      resonance. This form of resonance is shown to determine the optimal driving
      frequency for suppressing responses to asynchronous activity. Lastly, we
      demonstrate that the natural and resonant frequencies can be tuned by changes in
      neuronal excitability, the duration of feedback inhibition, and dynamic
      properties of the input. Our results predict that PFC networks are tuned for
      generating and selectively responding to beta- and gamma-rhythmic signals due to
      the natural and resonant properties of inhibition-based oscillators. They also
      suggest strategies for optimizing transcranial stimulation and using oscillatory
      networks in neuromorphic engineering.

PMID- 30091976
TI  - Diabetes prevalence in rural Indigenous Guatemala: A geographic-randomized cross
      sectional analysis of risk.
AB  - BACKGROUND: Developing countries and Indigenous populations are
      disproportionately affected by global trends in diabetes (T2DM), but inconsistent
      data are available to corroborate this pattern in Guatemala and indigenous
      communities in Central America. Historic estimates of T2DM, using a variety of
      sampling techniques and diagnostic methods, in Guatemala include a T2DM
      prevalence of: 4.2% (1970) and 8.4% (2003). Objectives of this geographically
      randomized, cross-sectional analysis of risk include: (1) use HbA1c to determine
      prevalence of T2DM and prediabetes in rural Indigenous community of Atitlan (2)
      identify risk factors for T2DM including age, BMI and gender. METHODS: A
      spatially random sampling method was used to identify 400 subjects. Prevalence
      was compared using the confidence interval method, and logistic regression and
      linear regression were used to assess association between diabetes and risk
      factors. FINDINGS: The overall prevalence of T2DM using HbA1c was 13.81% and
      prediabetes was also 13.81% in Atitlan, representing a tripling in diabetes from
      historic estimates and a large population with pre-diabetes. The probability of
      diabetes increased dramatically with increasing age, however no significant
      overall relationship existed with gender or BMI. CONCLUSIONS: Diabetes is a
      larger epidemic than previously expected and appears to be related to ageing
      rather than BMI. Our proposed explanations for these findings include: possible
      Indigenous unique genetic susceptibility to T2DM, shortcomings in BMI as a metric
      for adiposity in assessing risk, changes in lifestyle and diet, and an overall
      aging population. The conclusion of this study suggest that (1) T2DM in rural
      regions of Guatemala may be of epidemic proportion. With pre-diabetes, more than
      25% of the population will be diabetic in the very near future; (2) Age is a
      significant risk factor in the Indigenous population but BMI is not. This
      suggests that in some populations diabetes may be a disease of ageing.

PMID- 30091977
TI  - Transcriptome sequencing and ITRAQ reveal the detoxification mechanism of
      Bacillus GJ1, a potential biocontrol agent for Huanglongbing.
AB  - Huanglongbing (HLB) is the most serious disease affecting citrus production
      worldwide. No HLB-resistant citrus varieties exist. The HLB pathogen Candidatus
      Liberibacter asiaticus is nonculturable, increasing the difficulty of preventing
      and curing the disease. We successfully screened the biocontrol agent Bacillus
      GJ1 for the control of HLB in nursery-grown citrus plants. RNA sequencing (RNA
      seq) of the transcriptome and isobaric tags for relative and absolute
      quantification of the proteome revealed differences in the detoxification
      responses of Bacillus GJ1-treated and -untreated Ca. L. asiaticus-infected
      citrus. Phylogenetic tree alignment showed that GJ1 was classified as B.
      amyloliquefaciens. The effect of eliminating the HLB pathogen was measured using
      real-time quantitative polymerase chain reaction (qPCR) and PCR. The results
      indicate that the rate of detoxification reached 50% after seven irrigations, of
      plants with an OD600nm~1 Bacillus GJ1 suspension. Most importantly,
      photosynthesis-antenna proteins, photosynthesis, plant-pathogen interactions, and
      protein processing in the endoplasmic reticulum were significantly upregulated
      (padj < 0.05), as shown by the KEGG enrichment analysis of the transcriptomes;
      nine of the upregulated genes were validated by qPCR. Transcription factor
      analysis of the transcriptomes was performed, and 10 TFs were validated by qPCR.
      Cyanoamino acid metabolism, regulation of autophagy, isoflavonoid biosynthesis,
      starch and sucrose metabolism, protein export, porphyrin and chlorophyll
      metabolism, and carotenoid biosynthesis were investigated by KEGG enrichment
      analysis of the proteome, and significant differences were found in the
      expression of the genes involved in those pathways. Correlation analysis of the
      proteome and transcriptome showed common entries for the significantly different
      expression of proteins and the significantly different expression of genes in the
      GO and KEGG pathways, respectively. The above results reveal important
      information about the detoxification pathways.

PMID- 30091979
TI  - Dynamic changes in human-gut microbiome in relation to a placebo-controlled
      anthelminthic trial in Indonesia.
AB  - BACKGROUND: Microbiome studies suggest the presence of an interaction between the
      human gut microbiome and soil-transmitted helminth. Upon deworming, a complex
      interaction between the anthelminthic drug, helminths and microbiome composition
      might occur. To dissect this, we analyse the changes that take place in the gut
      bacteria profiles in samples from a double blind placebo controlled trial
      conducted in an area endemic for soil transmitted helminths in Indonesia.
      METHODS: Either placebo or albendazole were given every three months for a period
      of one and a half years. Helminth infection was assessed before and at 3 months
      after the last treatment round. In 150 subjects, the bacteria were profiled using
      the 454 pyrosequencing. Statistical analysis was performed cross-sectionally at
      pre-treatment to assess the effect of infection, and at post-treatment to
      determine the effect of infection and treatment on microbiome composition using
      the Dirichlet-multinomial regression model. RESULTS: At a phylum level, at pre
      treatment, no difference was seen in microbiome composition in terms of relative
      abundance between helminth-infected and uninfected subjects and at post
      treatment, no differences were found in microbiome composition between
      albendazole and placebo group. However, in subjects who remained infected, there
      was a significant difference in the microbiome composition of those who had
      received albendazole and placebo. This difference was largely attributed to
      alteration of Bacteroidetes. Albendazole was more effective against Ascaris
      lumbricoides and hookworms but not against Trichuris trichiura, thus in those who
      remained infected after receiving albendazole, the helminth composition was
      dominated by T. trichiura. DISCUSSION: We found that overall, albendazole does
      not affect the microbiome composition. However, there is an interaction between
      treatment and helminths as in subjects who received albendazole and remained
      infected there was a significant alteration in Bacteroidetes. This helminth
      albendazole interaction needs to be studied further to fully grasp the complexity
      of the effect of deworming on the microbiome. TRIAL REGISTRATION: ISRCTN Registy,
      ISRCTN83830814.

PMID- 30091978
TI  - A systems genetics resource and analysis of sleep regulation in the mouse.
AB  - Sleep is essential for optimal brain functioning and health, but the biological
      substrates through which sleep delivers these beneficial effects remain largely
      unknown. We used a systems genetics approach in the BXD genetic reference
      population (GRP) of mice and assembled a comprehensive experimental knowledge
      base comprising a deep "sleep-wake" phenome, central and peripheral
      transcriptomes, and plasma metabolome data, collected under undisturbed baseline
      conditions and after sleep deprivation (SD). We present analytical tools to
      interactively interrogate the database, visualize the molecular networks altered
      by sleep loss, and prioritize candidate genes. We found that a one-time, short
      disruption of sleep already extensively reshaped the systems genetics landscape
      by altering 60%-78% of the transcriptomes and the metabolome, with numerous
      genetic loci affecting the magnitude and direction of change. Systems genetics
      integrative analyses drawing on all levels of organization imply alpha-amino-3
      hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking and fatty
      acid turnover as substrates of the negative effects of insufficient sleep. Our
      analyses demonstrate that genetic heterogeneity and the effects of insufficient
      sleep itself on the transcriptome and metabolome are far more widespread than
      previously reported.

PMID- 30091980
TI  - Characterizing genetic and environmental influences on variable DNA methylation
      using monozygotic and dizygotic twins.
AB  - Variation in DNA methylation is being increasingly associated with health and
      disease outcomes. Although DNA methylation is hypothesized to be a mechanism by
      which both genetic and non-genetic factors can influence the regulation of gene
      expression, little is known about the extent to which DNA methylation at specific
      sites is influenced by heritable as well as environmental factors. We quantified
      DNA methylation in whole blood at age 18 in a birth cohort of 1,464 individuals
      comprising 426 monozygotic (MZ) and 306 same-sex dizygotic (DZ) twin pairs. Site
      specific levels of DNA methylation were more strongly correlated across the
      genome between MZ than DZ twins. Structural equation models revealed that
      although the average contribution of additive genetic influences on DNA
      methylation across the genome was relatively low, it was notably elevated at the
      highly variable sites characterized by intermediate levels of DNAm that are most
      relevant for epigenetic epidemiology. Sites at which variable DNA methylation was
      most influenced by genetic factors were significantly enriched for DNA
      methylation quantitative trait loci (mQTL) effects, and overlapped with sites
      where inter-individual variation correlates across tissues. Finally, we show that
      DNA methylation at sites robustly associated with environmental exposures such as
      tobacco smoking and obesity is also influenced by additive genetic effects,
      highlighting the need to control for genetic background in analyses of exposure
      associated DNA methylation differences. Estimates of the contribution of genetic
      and environmental influences to DNA methylation at all sites profiled in this
      study are available as a resource for the research community
      (http://www.epigenomicslab.com/online-data-resources).

PMID- 30091981
TI  - Phylogeny-corrected identification of microbial gene families relevant to human
      gut colonization.
AB  - The mechanisms by which different microbes colonize the healthy human gut versus
      other body sites, the gut in disease states, or other environments remain largely
      unknown. Identifying microbial genes influencing fitness in the gut could lead to
      new ways to engineer probiotics or disrupt pathogenesis. We approach this problem
      by measuring the statistical association between a species having a gene and the
      probability that the species is present in the gut microbiome. The challenge is
      that closely related species tend to be jointly present or absent in the
      microbiome and also share many genes, only a subset of which are involved in gut
      adaptation. We show that this phylogenetic correlation indeed leads to many false
      discoveries and propose phylogenetic linear regression as a powerful solution. To
      apply this method across the bacterial tree of life, where most species have not
      been experimentally phenotyped, we use metagenomes from hundreds of people to
      quantify each species' prevalence in and specificity for the gut microbiome. This
      analysis reveals thousands of genes potentially involved in adaptation to the gut
      across species, including many novel candidates as well as processes known to
      contribute to fitness of gut bacteria, such as acid tolerance in Bacteroidetes
      and sporulation in Firmicutes. We also find microbial genes associated with a
      preference for the gut over other body sites, which are significantly enriched
      for genes linked to fitness in an in vivo competition experiment. Finally, we
      identify gene families associated with higher prevalence in patients with Crohn's
      disease, including Proteobacterial genes involved in conjugation and fimbria
      regulation, processes previously linked to inflammation. These gene targets may
      represent new avenues for modulating host colonization and disease. Our strategy
      of combining metagenomics with phylogenetic modeling is general and can be used
      to identify genes associated with adaptation to any environment.

PMID- 30091982
TI  - pH-responsive polymer microcapsules for targeted delivery of biomaterials to the
      midgut of Drosophila suzukii.
AB  - Drosophila suzukii or spotted wing Drosophila is an economically important pest
      which can have a devastating impact on soft and stone fruit industries.
      Biological pesticides are being sought as alternatives to synthetic chemicals to
      control this invasive pest, but many are subject to degradation either in the
      environment or in the insect gut and as a result require protection. In this
      study we identified a sharp change in pH of the adult midgut from neutral to
      acidic (pH <3), which we then exploited to develop poly(2-vinylpyridine) (P2VP)
      microcapsules that respond to the change in midgut pH by dissolution and release
      of their cargo for uptake into the insect. First, we used labelled solid
      poly(methyl methacrylate) (PMMA) particles to show that microcapsules with a
      diameter less than 15 MUm are readily ingested by the adult insect. To
      encapsulate water-soluble biological species in an aqueous continuous phase, a
      multiple emulsion template was used as a precursor for the synthesis of pH
      responsive P2VP microcapsules with a fluorescent (FITC-dextran) cargo. The water
      soluble agent was initially separated from the aqueous continuous phase by an oil
      barrier, which was subsequently polymerised. The P2VP microcapsules were stable
      at pH > 6, but underwent rapid dissolution at pH < 4.2. In vivo studies showed
      that the natural acidity of the midgut of D. suzukii also induced the breakdown
      of the responsive P2VP microcapsules to release FITC-dextran which was taken up
      into the body of the insect and accumulated in the renal tubules.

PMID- 30091983
TI  - Diagnostic value of partial exome sequencing in developmental disorders.
AB  - Although intellectual disability is one of the major indications for genetic
      counselling, there are no homogenous diagnostic algorithms for molecular testing.
      While whole exome sequencing is increasingly applied, we questioned whether
      analyzing a partial exome, enriched for genes associated with Mendelian
      disorders, might be a valid alternative approach that yields similar detection
      rates but requires less sequencing capacities. Within this context 106 patients
      with different intellectual disability forms were analyzed for mutations in 4.813
      genes after pre-exclusion of copy number variations by array-CGH. Subsequent
      variant interpretation was performed in accordance with the ACMG guidelines. By
      this, a molecular diagnosis was established in 34% of cases and candidate
      mutations were identified in additional 24% of patients. Detection rates of
      causative mutations were above 30%, regardless of further symptoms, except for
      patients with seizures (23%). We did not detect an advantage from partial exome
      sequencing for patients with severe intellectual disability (36%) as compared to
      those with mild intellectual disability (44%). Specific clinical diagnoses pre
      existed for 20 patients. Of these, 5 could be confirmed and an additional 6 cases
      could be solved, but showed mutations in other genes than initially suspected. In
      conclusion partial exome sequencing solved >30% of intellectual disability cases,
      which is similar to published rates obtained by whole exome sequencing. The
      approach therefore proved to be a valid alternative to whole exome sequencing for
      molecular diagnostics in this cohort. The method proved equally suitable for both
      syndromic and non-syndromic intellectual disability forms of all severity grades.

PMID- 30091984
TI  - Normative data for handgrip strength in children and adolescents in the Maule
      Region, Chile: Evaluation based on chronological and biological age.
AB  - BACKGROUND: Hand grip strength (HGS) is associated with a number of causes
      resulting in cardiovascular death, in addition to bone fragility, and the
      presence of sarcopenia. The goal of our study was to analyze HGS of students
      based on chronological and biological age and propose normative standards for
      children and adolescents from Chile. METHODS: We studied 4604 school children of
      both sexes between the ages of 6.0 and 17.9 years of age. Weight, standing
      height, sitting height, and hand grip strength (HGS- right and left) were
      measured. The Body Mass Index (BMI) was calculated, and the biological age was
      calculated by using age at peak height velocity (APHV). RESULTS: When arranged by
      chronological age, no significant differences occurred in HGS between both sexes
      of school children from age 6 to 12 years of age. However, from ages 13 to 17,
      males showed greater HGS than females. Significant differences also emerged
      between both sexes and at all levels for biological age (APHV). For males,
      chronological age explained the HGS occurring between 0.74 to 0.75% and for
      females between 0.54 to 0.59%. For males, biological age explained the HGS for
      the range of 0.79 to 0.80% and 0.62 to 0.67% for females. The normative data for
      HGS for both sexes is expressed in percentiles. CONCLUSIONS: HGS during childhood
      and adolescence needs be analyzed and interpreted in terms of biological age
      rather than chronological age. The normative data to evaluate the HGS are a tool
      that can help professionals working in clinical and epidemiological contexts.

PMID- 30091985
TI  - Detecting suspicious activities at sea based on anomalies in Automatic
      Identification Systems transmissions.
AB  - Automatic Identification Systems (AIS) are a standard feature of ocean-going
      vessels, designed to allow vessels to notify each other of their position and
      route, to reduce collisions. Increasingly, the system is being used to monitor
      vessels remotely, particularly with the advent of satellite receivers. One
      fundamental problem with AIS transmission is the issue of gaps in transmissions.
      Gaps occur for three basic reasons: 1) saturation of the system in locations with
      high vessel density; 2) poor quality transmissions due to equipment on the vessel
      or receiver; and 3) intentional disabling of AIS transmitters. Resolving which of
      these mechanisms is responsible for generating gaps in transmissions from a given
      vessel is a critical task in using AIS to remotely monitor vessels. Moreover,
      separating saturation and equipment issues from intentional disabling is a key
      issue, as intentional disabling is a useful risk factor in predicting illicit
      behaviors such as illegal fishing. We describe a spatial statistical model
      developed to identify gaps in AIS transmission, which allows calculation of the
      probability that a given gap is due to intentional disabling. The model we
      developed successfully identifies high risk gaps in the test case example in the
      Arafura Sea. Simulations support that the model is sensitive to frequent gaps as
      short as one hour. Results in this case study area indicate expected high risk
      vessels were ranked highly for risk of intentional disabling of AIS transmitters.
      We discuss our findings in the context of improving enforcement opportunities to
      reduce illicit activities at sea.

PMID- 30091986
TI  - Sensory modulation dysfunction is associated with Complex Regional Pain Syndrome.
AB  - OBJECTIVE: Complex Regional Pain Syndrome (CRPS), a chronic pain condition,
      develops mainly after limb trauma and severely inhibits function. While early
      diagnosis is essential, factors for CRPS onset are elusive. Therefore,
      identifying those at risk is crucial. Sensory modulation dysfunction (SMD),
      affects the capacity to regulate responses to sensory input in a graded and
      adaptive manner and was found associated with hyperalgesia in otherwise healthy
      individuals, suggestive of altered pain processing. AIM: To test SMD as a
      potential risk factor for CRPS. METHODS: In this cross-sectional study, forty
      four individuals with CRPS (29.9+/-11 years, 27 men) and 204 healthy controls
      (27.4+/-3.7 years, 105 men) completed the Sensory Responsiveness Questionnaire
      Intensity Scale (SRQ-IS). A physician conducted the CRPS Severity Score (CSS),
      testing individuals with CRPS. RESULTS: Thirty-four percent of the individuals
      with CRPS and twelve percent of the healthy individuals were identified to have
      SMD (chi2 (1) = 11.95; p<0.001). Logistic regression modeling revealed that the
      risk of CRPS is 2.68 and 8.21 times higher in individuals with sensory over- and
      sensory under-responsiveness, respectively, compared to non-SMD individuals (p =
      0.03 and p = 0.01, respectively). CONCLUSIONS: SMD, particularly sensory under
      responsiveness, might serve as a potential risk factor for CRPS and therefore
      screening for SMD is recommended. This study provides the risk index probability
      clinical tool a simple evaluation to be applied by clinicians in order to
      identify those at risk for CRPS immediately after injury. Further research is
      needed.

PMID- 30091988
TI  - Object exploration facilitates 4-month-olds' mental rotation performance.
AB  - How do infants learn to mentally rotate objects, to imagine them rotating through
      different viewpoints? One possibility is that development of infants' mental
      rotation (MR) is facilitated by visual and manual experience with complex
      objects. To evaluate this possibility, eighty 4-month-olds (40 females, 40 males)
      participated in an object exploration task with Velcro "sticky mittens" that
      allow infants too young to grasp objects themselves to nonetheless explore those
      objects manually as well as visually. These eighty infants also participated in a
      visual habituation task designed to test MR. Half the infants (Mittens First
      group) explored the object prior to the MR task, and the other half afterwards
      (Mittens Second group), to examine the role of immediate prior object experience
      on MR performance. We compared performance of male and female infants, but found
      little evidence for sex differences. However, we found an important effect of
      object exploration: The infants in the Mittens First group who exhibited the
      highest levels of spontaneous object engagement showed the strongest evidence of
      MR, but there were no consistent correlations between these measures for infants
      in the Mittens Second group. These findings suggest an important contribution
      from object experience to development of MR.

PMID- 30091987
TI  - The Arrows and Colors Cognitive Test (ACCT): A new verbal-motor free cognitive
      measure for executive functions in ALS.
AB  - BACKGROUND AND OBJECTIVE: The presence of executive deficits in patients with
      Amyotrophic Lateral Sclerosis is well established, even if standardized measures
      are difficult to obtain due to progressive physical disability of the patients.
      We present clinical data concerning a newly developed measure of cognitive
      flexibility, administered by means of Eye-Tracking (ET) technology in order to
      bypass verbal-motor limitations. METHODS: 21 ALS patients and 21 age-and
      education-matched healthy subjects participated in an ET-based cognitive
      assessment, including a newly developed test of cognitive flexibility (Arrows and
      Colors Cognitive Test-ACCT) and other oculomotor-driven measures of cognitive
      functions. A standard screening of frontal and working memory abilities and
      global cognitive efficiency was administered to all subjects, in addition to a
      psychological self-rated assessment. For ALS patients, a clinical examination was
      also performed. RESULTS: ACCT successfully discriminated between patients and
      healthy controls, mainly concerning execution times obtained at different
      subtests. A qualitative analysis performed on error distributions in patients
      highlighted a lower prevalence of perseverative errors, with respect to other
      type of errors. Correlations between ACCT and other ET-based frontal-executive
      measures were significant and involved different frontal sub-domains. Limited
      correlations were observed between ACCT and standard 'paper and pencil' cognitive
      tests. CONCLUSIONS: The newly developed ET-based measure of cognitive flexibility
      could be a useful tool to detect slight frontal impairments in non-demented ALS
      patients by bypassing verbal-motor limitations through the oculomotor-driven
      administration. The findings reported in the present study represent the first
      contribution towards the development of a full verbal-motor free executive test
      for ALS patients.

PMID- 30091989
TI  - Risk of retinal artery occlusion in patients with diabetes mellitus: A
      retrospective large-scale cohort study.
AB  - There is a globally increasing prevalence and incidence of diabetes mellitus
      (DM). Prolonged hyperglycaemia could lead to both macrovascular damage, such as
      carotid artery atherosclerosis, and microvascular damage, such as retinal
      arteriolar narrowing, and might contribute to retinal artery occlusion (RAO).
      Accordingly, it is important to determine whether DM is a contrubuting factor of
      RAO. We conducted a retrospective cohort study that included 241,196 DM patients
      from the Longitudinal Cohort of Diabetes Patients Database who were recruited
      between 2003 and 2005. An age- and sex-matched non-DM control group included the
      same number of patients who were selected from the Taiwan Longitudinal Health
      Insurance Database of 2000. Relevant data of each patient were collected from the
      index date until December 2013. The incidence and risk of RAO were calculated and
      compared between the DM and non-DM groups. The hazard ratio for RAO was
      calculated using Cox proportional hazards regression analysis after adjusting for
      confounders. The cumulative incidence rate of RAO was calculated by Kaplan-Meier
      analysis. In total, 317 patients with DM and 144 controls developed RAO during
      the follow-up period, leading to an incidence rate of RAO in DM patients that was
      2.30 times (95% confidence interval [CI] = 1.89-2.80) greater than that in
      controls. After adjustment for potential confounders, patients with DM were 2.11
      times (95% CI, 1.71-2.59) more likely to develop RAO in the total study cohort.
      In conclusion, DM increases the risk of RAO, which is an interdisciplinary
      emergency. Close collaboration between endocrinologists and ophthalmologists is
      important in managing RAO following DM.

PMID- 30091990
TI  - Characterization of candidate genes involved in halotolerance using high
      throughput omics in the halotolerant bacterium Virgibacillus chiguensis.
AB  - We previously used whole-genome sequencing and Tn5 transposon mutagenesis to
      identify 16 critical genes involved in the halotolerance of Halomonas
      beimenensis, a species in the phylum Proteobacteria. In this present study, we
      sought to determine if orthologous genes in another phylum are also critical for
      halotolerance. Virgibacillus spp. are halotolerant species that can survive in
      high-saline environments. Some Virgibacillus species are used in different
      aspects of food processing, compatible solute synthesis, proteinase production,
      and wastewater treatment. However, genomic information on Virgibacillus
      chiguensis is incomplete. We assembled a draft V. chiguensis strain NTU-102
      genome based on high-throughput next-generation sequencing (NGS) and used
      transcriptomic profiling to examine the high-saline response in V. chiguensis.
      The V. chiguensis draft genome is approximately 4.09 Mbp long and contains 4,166
      genes. The expression profiles of bacteria grown in 5% and 20% NaCl conditions
      and the corresponding Gene Ontology (GO) and clusters of orthologous groups (COG)
      categories were also analyzed in this study. We compared the expression levels of
      these 16 orthologs of halotolerance-related genes in V. chiguensis and H.
      beimenensis. Interestingly, the expression of 7 of the 16 genes, including trkA2,
      smpB, nadA, mtnN2, rfbP, lon, and atpC, was consistent with that in H.
      beimenensis, suggesting that these genes have conserved functions in different
      phyla. The omics data were helpful in exploring the mechanism of saline
      adaptation in V. chiguensis, and our results indicate that these 7 orthologs may
      serve as biomarkers for future screening of halotolerant species in the future.

PMID- 30091991
TI  - Climate variability impacts on rice production in the Philippines.
AB  - Changes in crop yield and production over time are driven by a combination of
      genetics, agronomics, and climate. Disentangling the role of these various
      influences helps us understand the capacity of agriculture to adapt to change.
      Here we explore the impact of climate variability on rice yield and production in
      the Philippines from 1987-2016 in both irrigated and rainfed production systems
      at various scales. Over this period, rice production is affected by variations in
      soil moisture, which are largely driven by the El Nino-Southern Oscillation
      (ENSO). We found that the climate impacts on rice production are strongly
      seasonally modulated and differ considerably by region. As expected, rainfed
      upland rice production systems are more sensitive to soil moisture variability
      than irrigated paddy rice. About 10% of the variance in rice production anomalies
      on the national level co-varies with soil moisture changes, which in turn are
      strongly negatively correlated with an index capturing ENSO variability. Our
      results show that while temperature variability is of limited importance in the
      Philippines today, future climate projections suggest that by the end of the
      century, temperatures might regularly exceed known limits to rice production if
      warming continues unabated. Therefore, skillful seasonal prediction will likely
      become increasingly crucial to provide the necessary information to guide
      agriculture management to mitigate the compounding impacts of soil moisture
      variability and temperature stress. Detailed case studies like this complement
      global yield studies and provide important local perspectives that can help in
      food policy decisions.

PMID- 30091992
TI  - Synthesis of electrospun polyacrylonitrile- derived carbon fibers and comparison
      of properties with bulk form.
AB  - This study deals with the fabrication of polyacrylonitrile (PAN) nanofibers via
      an electrospinning process followed by stabilizing and carbonization in order to
      remove all non-carboneous matter and ensure a pure carboneous material. The as
      spun PAN fibers were stabilized in air at 270 degrees C for one hour and then
      carbonized at 750, 850, and 950 degrees C in an inert atmosphere (argon) for
      another one hour. Differential scanning calorimetry and Raman spectroscopy were
      employed to determine the thermal and chemical properties of PAN. Surface
      features and morphologies of PAN-derived carbon nanofibers were investigated by
      means of scanning electron microscopy (SEM). SEM micrograms showed that fiber
      diameters were reduced after carbonization due to evolution of toxic gases and
      dehydrogenation. The Raman spectra of carbonized fibers manifested D/G peaks. The
      Raman spectroscopy peaks of 1100 and 500 cm-1 manifested the formation of gamma
      phase and another peak at 900 cm-1 manifested the formation of alpha-phase. The
      water contact angle measurement of carbonized PAN fibers indicated that the
      nanofibers were superhydrophobic (theta > 150o) due to the formation of bumpy and
      pitted surface after carbonization. In DSC experiment, the stabilized fibers
      showed a broad exothermic peak at 308 degrees C due to cyclization process. The
      mechanical andThermal analysis was used to ascertain mechanical properties of
      carbonized PAN fibers. PAN-derived carbon nanofibers possess excellent physica
      and mechanical properties and therefore, they may be suitable for many industrial
      applications such as energy, biomedical, and aerospace.

PMID- 30091993
TI  - Comparison of two different methods of image analysis for the assessment of
      microglial activation in patients with multiple sclerosis using (R)-[N-methyl
      carbon-11]PK11195.
AB  - Chronic active multiple sclerosis (MS) lesions have a rim of activated
      microglia/macrophages (m/M) leading to ongoing tissue damage, and thus represent
      a potential treatment target. Activation of this innate immune response in MS has
      been visualized and quantified using PET imaging with [11C]-(R)-PK11195 (PK).
      Accurate identification of m/M activation in chronic MS lesions requires the
      sensitivity to detect lower levels of activity within a small tissue volume. We
      assessed the ability of kinetic modeling of PK PET data to detect m/M activity in
      different central nervous system (CNS) tissue regions of varying sizes and in
      chronic MS lesions. Ten patients with MS underwent a single brain MRI and two PK
      PET scans 2 hours apart. Volume of interest (VOI) masks were generated for the
      white matter (WM), cortical gray matter (CGM), and thalamus (TH). The
      distribution volume (VT) was calculated with the Logan graphical method (LGM-VT)
      utilizing an image-derived input function (IDIF). The binding potential (BPND)
      was calculated with the reference Logan graphical method (RLGM) utilizing a
      supervised clustering algorithm (SuperPK) to determine the non-specific binding
      region. Masks of varying volume were created in the CNS to assess the impact of
      region size on the various metrics among high and low uptake regions. Chronic MS
      lesions were also evaluated and individual lesion masks were generated. The
      highest PK uptake occurred the TH and lowest within the WM, as demonstrated by
      the mean time activity curves. In the TH, both reference and IDIF based methods
      resulted in estimates that did not significantly depend on VOI size. However, in
      the WM, the test-retest reliability of BPND was significantly lower in the
      smallest VOI, compared to the estimates of LGM-VT. These observations were
      consistent for all chronic MS lesions examined. In this study, we demonstrate
      that BPND and LGM-VT are both reliable for quantifying m/M activation in regions
      of high uptake, however with blood input function LGM-VT is preferred to assess
      longitudinal m/M activation in regions of relatively low uptake, such as chronic
      MS lesions.

PMID- 30091995
TI  - High effective time-dependent THz spectroscopy method for the detection and
      identification of substances with inhomogeneous surface.
AB  - We discuss an effective time-dependent THz spectroscopy method for the detection
      and identification of a substance with an inhomogeneous surface using a broadband
      THz signal reflected from the substance. We show that a successful and reliable
      identification can be made using the single long-duration THz signal, which
      contains not only the main reflected pulse, but also several sub-pulses. The
      method does not use averaging of the measured THz signals over the viewing angles
      and scanning over the surface area, which significantly increases the signal
      processing speed. The identification is based on the method of spectral dynamics
      analysis together with the integral correlation criteria (ICC). We compare the
      absorption spectral dynamics of a substance under analysis with the corresponding
      dynamics for a standard substance from database. For reliable and effective
      substance detection, we propose to use several ICC simultaneously in different
      time intervals, which contain not only the main pulse of the reflected THz
      signal, but also the sub-pulses. This way, one can detect and identify the
      substance in the sample with high probability. As examples of identification, we
      used the THz signals reflected from the plastic explosive PWM C4 with both rough
      and concave surface. We show that the main pulse, reflected from the
      inhomogeneous surface of the sample, contains information about its absorption
      frequencies.

PMID- 30091994
TI  - STAT3 expression is a prognostic marker in upper urinary tract urothelial
      carcinoma.
AB  - Signal transducer and activator of transcription 3 (STAT3) plays a prominent role
      in the growth and invasion of several types of solid tumors. In this study, to
      assess the expression status and prognostic significance of the STAT3 pathway in
      upper urinary tract urothelial carcinoma (UTUC), we immunohistochemically stained
      for STAT3 and STAT3 pathway proteins, sphingosine-1-phosphate receptor 1 (S1PR1)
      and interleukin-6 (IL-6), in a tissue microarray containing 99 UTUC specimens.
      There were no significant associations between STAT3, S1PR1, or IL-6 expression
      pattern and tumor grade or pT stage. However, the patients with high STAT3 tumor
      had a significantly higher risk of both disease progression (p = 0.009) and
      cancer-specific mortality (p = 0.009), but not with tumors expressing S1PR1 or IL
      6. High STAT3 expression in the nucleus was also associated with a significantly
      higher risk of both disease progression (p = 0.003) and cancer-specific mortality
      (p = 0.034). Multivariate analysis revealed that high STAT3 expression in the
      nucleus was significantly associated with cancer-specific survival after
      adjustment for pathological stage, lymph node involvement, lymphovascular
      invasion, and tumor grade (HR = 2.136, 95% CI = 1.009-4.767, p = 0.047). Our
      findings indicated that STAT3 could be a cancer-promoting factor and potentially
      a significant prognostic factor in UTUC.

PMID- 30091996
TI  - A model to predict nodal metastasis in patients with oral squamous cell
      carcinoma.
AB  - Difficulty in precise decision making on necessity of surgery is a major problem
      when managing oral squamous cell carcinomas (OSCCs) with clinically negative
      neck. Therefore, use of clinical and histopathological parameters in combination
      would be important to improve patient management. The main objective is to
      develop a model that predicts the presence of nodal metastasis in patients with
      OSCC.623 patients faced neck dissections with buccal mucosal or tongue squamous
      cell carcinoma (SCC) were selected from patients' records. Demographic data,
      clinical information, nodal status, Depth of invasion (DOI) and pattern of
      invasion (POI) were recorded. The parameters which showed a significant
      association with nodal metastasis were used to develop a multivariable predictive
      model (PM). Univariate logistic regression was used to estimate the strengths of
      those associations in terms of odds ratios (OR). This showed statistically
      significant associations between status of the nodal metastasis and each of the
      following 4 histopathological parameters individually: size of the tumour (T),
      site, POI, and DOI. Specifically, OR of nodal metastasis for tongue cancers
      relative to buccal mucosal cancers was 1.89, P-value < 0.001. Similarly, ORs for
      POI type 3 and 4 relative to type 2 were 1.99 and 5.83 respectively. A similar
      relationship was found with tumour size; ORs for T2, T3, and T4 compared to T1
      were 2.79, 8.27 and 8.75 respectively. These four histopathological parameters
      were then used to develop a predictive model for nodal metastasis. This model
      showed that probability of nodal metastasis is higher among tongue cancers with
      increasing POI, with increasing T, and with larger depths while other
      characteristics remained unchanged. The proposed model provides a way of using
      combinations of histopathological parameters to identify patients with higher
      risks of nodal metastasis for surgical management.

PMID- 30091998
TI  - Estimating the future health and aged care expenditure in Australia with changes
      in morbidity.
AB  - AIMS: We estimate the pure effect of ageing on total health and aged care
      expenditure in Australia in the next 20 years. METHODS: We use a simple
      demographic projection model for the number of people in older age groups along
      with a needs based estimate of changes in the public and private cost of care per
      person in each group adjusted for expected changes in morbidity. RESULTS: A pure
      ageing model of expenditure growth predicts an increase in health expenditure per
      elderly person from $7439 in 2015 to $9594 in 2035 and an increase in total
      expenditure from $166 billion to $320 billion (an average annual growth of
      3.33%). If people live longer without additional morbidity, then total health
      expenditure only grows at an average annual rate of 0.48%. If only some of those
      additional years are in good health, then the average year on year growth is
      1.87%. CONCLUSION: Ageing will have a direct effect on the growth of health
      spending but is likely to be dwarfed by other demand and supply factors. A focus
      on greater efficiency in health production and finance is likely to be more
      effective in delivering high quality care than trying to restrain the demand for
      health and aged care among the elderly.

PMID- 30091997
TI  - Correlation of microbiological yield with radiographic activity on chest computed
      tomography in cases of suspected pulmonary tuberculosis.
AB  - BACKGROUND: Little is known about the correlation between microbiological yield
      and radiographic activity, on chest computed tomography (CT), in suspected
      pulmonary tuberculosis (PTB) cases, despite CT being widely used, clinically.
      METHODS: We used multicenter retrospective data, obtained from medical records,
      focusing on the diagnostic performance for definite PTB. We categorized patients
      into four groups, by radiographic activity: definitely active, probably active,
      indeterminate activity, and probably inactive. RESULTS: Of the 650 patients
      included, 316 had culture-confirmed PTB; 190 (29.2%), 323 (49.7%), 70 (10.8%),
      and 67 (10.3%) were classified into the definitely active, probably active,
      indeterminate activity, and probably inactive groups, respectively. The
      corresponding observed culture rates for CT radiographic activity were 61.6%,
      60.7%, 4.3% and 0%, respectively. When not only culture rates but TB-PCR and
      histological results were taken into consideration as definite PTB, it showed
      66.6%, 67.2%, 14.3%, and 0% of each CT radiographic activity, respectively.
      Regarding the diagnostic performance for definite PTB, radiographic activity
      displayed high sensitivity (97.1%, 95% confidence interval (CI), 94.6-98.5) and
      negative predictive values (92.7%, 95% CI, 86.6-96.2), considered definitely and
      probably active PTB. Apart from PTB, other etiologies, according to radiographic
      activity, were predominantly respiratory infections such as bacterial pneumonia
      and non-tuberculous mycobacterial infection. CONCLUSIONS: Radiographic activity
      showed good diagnostic performance, and can be used easily in clinical practice.
      However, clinicians should consider other possibilities, because radiologic
      images do not confirm microbiological PTB.

PMID- 30092001
TI  - Prevalence and genotyping of Trichomonas infections in wild birds in central
      Germany.
AB  - Avian trichomonosis is a widespread disease in columbids and other birds, caused
      by ingestion of the unicellular flagellate Trichomonas gallinae which proliferate
      primarily in the upper respiratory tracts. Studies using genetic analyses have
      determined some highly pathogenic lineages in birds, but the prevalence and
      distribution of potentially pathogenic and non-pathogenic T. gallinae lineages in
      wild birds is still not well known. We examined 440 oral swab samples of 35 bird
      species collected between 2015 and 2017 in Hesse, central Germany, for
      Trichomonas spp. infection and for determining the genetic lineages. Of these
      birds, 152 individuals were caught in the wild and 288 individuals were admitted
      from the wild to a veterinary clinic. The overall Trichomonas spp. prevalence was
      35.6%. We observed significant differences between bird orders, with the highest
      prevalence in owls (58%) and columbids (50%), while other orders had slightly
      lower prevalences, with 36% in Accipitriformes, 28% in Falconiformes and 28% in
      Passeriformes. Among 71 successfully sequenced samples, we found 13 different
      haplotypes, including two previously described common lineages A/B (20 samples)
      and C/V/N (36 samples). The lineage A/B has been described as pathogenic, causing
      lesions and mortality in columbids, raptors and finches. This lineage was found
      in 11 of the 35 species, including columbids (feral pigeon, woodpigeon, stock
      dove), passerines (greenfinch, chaffinch, blackbird) and raptors (common kestrel,
      sparrowhawk, red kite, peregrine falcon and common buzzard). One new lineage (R)
      was found in a sample of a chaffinch. In conclusion, we found that the prevalence
      of Trichomonas spp. infection in wild birds was high overall, and the potentially
      pathogenic lineage A/B was widespread. Our findings are worrying, as epidemic
      outbreaks of trichomonosis have already been observed in Germany in several years
      and can have severe negative effects on bird populations. This disease may add to
      the multiple pressures that birds face in areas under high land-use intensity.

PMID- 30091999
TI  - Aryl hydrocarbon receptor (AHR) is a novel druggable pathway controlling
      malignant progenitor proliferation in chronic myeloid leukemia (CML).
AB  - Aryl Hydrocarbon Receptor (AHR) is an ubiquitous basic helix-loop-helix
      transcription factor, which is ligand-activated and involved in numerous
      biological processes including cell division, cell quiescence and inflammation.
      It has been shown that AHR is involved in normal hematopoietic progenitor
      proliferation in human cells. In addition, loss of AHR in knockout mice is
      accompanied by a myeloproliferative syndrome-like disease, suggesting a role of
      AHR in hematopoietic stem cell (HSC) maintenance. To study the potential role of
      AHR pathway in CML progenitors and stem cells, we have first evaluated the
      expression of AHR in UT-7 cell line expressing BCR-ABL. AHR expression was highly
      reduced in UT-7 cell expressing BCR-ABL as compared to controls. AHR transcript
      levels, quantified in primary peripheral blood CML cells at diagnosis (n = 31
      patients) were found to be significantly reduced compared to healthy controls (n
      = 15). The use of StemRegenin (SR1), an AHR antagonist, induced a marked
      expansion of total leukemic cells and leukemic CD34+ cells by about 4- and 10
      fold respectively. SR1-treated CML CD34+ cells generated more colony-forming
      cells and long-term culture initiating cell (LTC-IC)-derived progenitors as
      compared to non-SR1-treated counterparts. Conversely, treatment of CML CD34+
      cells with FICZ, a natural agonist of AHR, induced a 3-fold decrease in the
      number of CD34+ cells in culture after 7 days. Moreover, a 4-day FICZ treatment
      was sufficient to significantly reduce the clonogenic potential of CML CD34+
      cells and this effect was synergized by Imatinib and Dasatinib treatments.
      Similarly, a 3-day FICZ treatment contributed to hinder significantly the number
      of LTC-IC-derived progenitors without synergistic effect with Imatinib. The
      analysis of molecular circuitry of AHR signaling in CML showed a transcriptional
      signature in CML derived CD34+ CD38- primitive cells with either low or high
      levels of AHR, with an upregulation of myeloid genes involved in differentiation
      in the "AHR low" fraction and an upregulation of genes involved in stem cell
      maintenance in the "AHR high" fraction. In conclusion, these findings demonstrate
      for the first time that down-regulation of AHR expression, a major cell cycle
      regulator, is involved in the myeloproliferative phenotype associated with CML.
      AHR agonists inhibit clonogenic and LTC-IC-derived progenitor growth and they
      could be used in leukemic stem cell targeting in CML.

PMID- 30092000
TI  - The positioning of the asymmetric septum during sporulation in Bacillus subtilis.
AB  - Probably one of the most controversial questions about the cell division of
      Bacillus subtilis, a rod-shaped bacterium, concerns the mechanism that ensures
      correct division septum placement-at mid-cell during vegetative growth but closer
      to one end during sporulation. In general, bacteria multiply by binary fission,
      in which the division septum forms almost exactly at the cell centre. How the
      division machinery achieves such accuracy is a question of continuing interest.
      We understand in some detail how this is achieved during vegetative growth in
      Escherichia coli and B. subtilis, where two main negative regulators, nucleoid
      occlusion and the Min system, help to determine the division site, but we still
      do not know exactly how the asymmetric septation site is determined during
      sporulation in B. subtilis. Clearly, the inhibitory effects of the nucleoid
      occlusion and Min system on polar division have to be overcome. We evaluated the
      positioning of the asymmetric septum and its accuracy by statistical analysis of
      the site of septation. We also clarified the role of SpoIIE, RefZ and MinCD on
      the accuracy of this process. We determined that the sporulation septum forms
      approximately 1/6 of a cell length from one of the cell poles with high precision
      and that SpoIIE, RefZ and MinCD have a crucial role in precisely localizing the
      sporulation septum. Our results strongly support the idea that asymmetric septum
      formation is a very precise and highly controlled process regulated by a still
      unknown mechanism.

PMID- 30092002
TI  - Optimizing patient's selection for prostate biopsy: A single institution
      experience with multi-parametric MRI and the 4Kscore test for the detection of
      aggressive prostate cancer.
AB  - OBJECTIVES: To evaluate the performance of mpMRI and the 4Kscore test together
      for the detection of significant prostate cancer. Material and methods We
      selected a consecutive series of men who were referred for evaluation of prostate
      cancer at an academic institution and underwent mpMRI and the 4Kscore test. The
      primary outcome was the presence of Gleason 7 or higher cancer on biopsy of the
      prostate. We used logistic regression and Decision Curve Analysis to report the
      discrimination and clinical utility of using mpMRI and the 4Kscore test for
      prostate cancer detection. We modeled the probability of harboring a Gleason 7 or
      higher prostate cancer based on the 4Kscore test and mpMRI findings. Finally, we
      examined various combinations and sequences of mpMRI and the 4Kscore test and
      assessed the impact on biopsies avoided and cancers missed. RESULTS: Among 300
      men who underwent a 4Kscore test and mpMRI, 149 (49%) underwent a biopsy. Among
      those, 73 (49%) had cancer, and 49 (33%) had Gleason 7 cancer. The area under the
      curve (AUC) for using the 4Kscore test and mpMRI together 0.82 (0.75-0.89) was
      superior to using the 4Kscore 0.70 (0.62-0.79) or mpMRI 0.74 (0.66-0.81)
      individually (p = 0.001). Similarly, decision analysis revealed the highest net
      benefit was achieved using both tests. CONCLUSIONS: The 4Kscore test and mpMRI
      results provide independent, but complementary, information that enhances the
      prediction of higher-grade prostate cancer and improves patient's selection for a
      prostate biopsy. Prospective trials are required to confirm these findings.

PMID- 30092005
TI  - The development and validation of a new interprofessional team approach
      evaluation scale.
AB  - A team approach in health care involves an interprofessional approach to patient
      care. We wanted to develop and validate a tool that would evaluate the
      interprofessional team approach to patients of a family medicine team. We
      performed a descriptive study in three consecutive phases: a literature review,
      consensus development panels, and a cross-sectional validation study. Three
      rounds of consensus development panels were carried out in order to evaluate and
      adapt the initial scale. The cross-sectional study was carried out in all
      Slovenian family medicine practices, each invited 10 consecutive patients. In the
      quantitative study, 3,292 patients participated (a 50.7% response rate), of which
      1,810 (55.0%) were women. The mean age of the sample was 53.1 +/- 1.2 years. The
      final Cronbach's alpha was 0.901. A factor analysis of the 9-item scale put
      forward two factors (Team Approach and Person-Centred approach) which explained
      68.6% of the variance. This study provided a new scale for the evaluation of
      patient satisfaction with the interprofessional family medicine team from the
      patients' point of view. It opened the question of family medicine team
      competencies and pointed towards the need to develop a family medicine
      interprofessional team competency framework and a comprehensive tool for its
      assessment.

PMID- 30092004
TI  - Differential effects of angiotensin II type I receptor blockers on reducing
      intraocular pressure and TGFbeta signaling in the mouse retina.
AB  - PURPOSE: Angiotensin II type 1 receptor blockers (ARBs) have been investigated
      for their neuroprotective and intraocular pressure (IOP) lowering effects in
      treating glaucoma, but the reports have been inconsistent possibly because
      different compounds and models have been used. Here we selected three ARBs for
      head-to-head comparisons of their effects on IOP and transforming growth factor
      beta (TGFbeta) signaling, which is believed to play an important role in glaucoma
      pathogenesis. METHODS: Three ARBs (losartan, irbesartan or telmisartan) or
      vehicle controls were administered via chow to C57BL/6J mice for up to 7 days.
      Drug concentrations in the eye, brain, and plasma were evaluated by liquid
      chromatography mass spectrometry. Cohorts of mice were randomly assigned to
      different treatments. IOP and blood pressure were measured before and after ARB
      treatment. Effects of ARBs on TGFbeta signaling in the retina were evaluated by
      phosphorylated Smad2 (pSmad2) immunohistochemistry. RESULTS: Physiologically
      relevant concentrations of losartan, irbesartan and telmisartan were detected in
      eye, brain and plasma after drug administration (n = 11 mice/treatment). Blood
      pressure was significantly reduced by all ARBs compared to vehicle-fed controls
      (all p-values < 0.001, n = 8-15 mice/treatment). Compared to vehicle control, IOP
      was significantly reduced by irbesartan (p = 0.030) and telmisartan (p = 0.019),
      but not by losartan (n = 14-17 mice/treatment). Constitutive pSmad2 fluorescence
      observed in retinal ganglion cells was significantly reduced by telmisartan (p =
      0.034), but not by losartan or irbesartan (n = 3-4 mice/treatment). CONCLUSIONS:
      Administration via chow is an effective delivery method for ARBs, as evidenced by
      lowered blood pressure. ARBs vary in their abilities to lower IOP or reduce
      TGFbeta signaling. Considering the significant roles of IOP and TGFbeta in
      glaucoma pathogenesis, specific ARBs with dual effects, such as telmisartan, may
      be more effective than other ARBs for treating glaucoma.

PMID- 30092003
TI  - Differential chemokine expression under the control of peripheral blood
      mononuclear cells issued from Alzheimer's patients in a human blood brain barrier
      model.
AB  - Growing evidence highlights the peripheral blood mononuclear cells (PBMCs) role
      and the chemokine involvement in the Alzheimer's disease (AD) physiopathology.
      However, few data are available about the impact of AD PBMCs in the chemokine
      signature in a brain with AD phenotype. Therefore, this study analyzed the
      chemokine levels in a human blood brain barrier model. A human endothelial cell
      line from the immortalized cerebral microvascular endothelial cell line
      (hCMEC/D3) and a human glioblastoma U-87 MG cell line, both with no AD phenotype
      were used while PBMCs came from AD at mild or moderate stage and control
      patients. PBMCs from moderate AD patients decreased CCL2 and CCL5 levels in
      endothelial, and also CXCL10 in abluminal compartments and in PBMCs compared to
      PBMCs from mild AD patients. The CX3CL1 expression increased in endothelial and
      abluminal compartments with PBMCs from mild AD patients compared to controls. AD
      PBMCs can convert the chemokine signature towards that found in AD brain,
      targeting some chemokines as new biomarkers in AD.

PMID- 30092006
TI  - Generalized logistic functions in modelling emergence of Brassica napus L.
AB  - The objective of this study was to determine whether generalized logistic
      functions (Richards model with time shift) may be used to predict emergence of
      winter rapeseed (Brassica napus L.) after its seed treatment with plant extracts
      from Taraxacum officinale roots under controlled environment conditions.
      Emergence analyses were conducted for winter rape whose seeds were treated with a
      plant extract and for the non-treated seeds sown to the soil at the site of
      earlier point application of the extract. Curves were plotted for experimental
      data by minimizing the square sum of differences between the experimental data
      and the mathematical model. To evaluate model fit, the mean squared error was
      divided into four factors. Computing modelling efficiency coefficients were also
      introduced to enable complete analysis. Results of simulation research
      demonstrate that the determined parameters of curves (e.g. values of growth
      parameters, time shift or the upper limit of population) describing the number of
      seedlings in the function of time stayed compliant to the interpretation with
      regard to the biology of the analyzed processes. The proposed mathematical
      description based on generalized logistic functions showed extraordinary fit (r =
      0.999) to the experimental data, which makes it highly useful in predictive
      control of rapeseed emergence. In addition, the study enabled concluding that
      plant extracts application to the soil allowed achieving a higher maximal
      emergence rate compared to the control sample. The application of the plant
      extracts increased the final population of rapeseed and significantly accelerated
      the occurrence of the maximal emergence rate.

PMID- 30092007
TI  - Does mindfulness training modulate the influence of spatial attention on the
      processing of intracutaneous electrical stimuli?
AB  - Mindfulness based stress reduction (MBSR) training has been proposed to improve
      attentional skills by modulating thalamo-cortical loops that affect the
      sensitivity of relevant cortical areas like the somatosensory cortex. This
      modulation may be reflected in the electroencephalographic (EEG) alpha rhythm,
      and could affect the processing of subsequently applied intracutaneous electrical
      stimuli. Participants took part in an MBSR training and participated in two EEG
      sessions. EEG was measured in variants of an endogenous orienting paradigm in
      which attention had to be directed to the left or right forearm. After the
      orienting interval, the electrical stimulus was applied, equally likely on the
      attended or the unattended forearm. One group of participants took part in the
      EEG session before and after the training, while the other group took part after
      the training, and another time, eight weeks later. The influence of the MBSR
      training and spatial attention were examined with behavioral measures,
      lateralized alpha power within the orienting interval, and with event-related
      potentials (ERPs) evoked by the electrical stimuli. Self-reported mindfulness was
      clearly affected by the training, but no influence was found on other behavioral
      measures. Alpha power was clearly lateralized due to spatial attention and
      several ERP components (N130, N180, P340) were modulated by spatial attention but
      no support was found for an influence of the MBSR training. Finally, analyses
      revealed that individual differences in training time modulated some of the
      observed effects, but no support was found for an influence on attentional
      orienting.

PMID- 30092008
TI  - Ethnicity estimation using family naming practices.
AB  - This paper examines the association between given and family names and self
      ascribed ethnicity as classified by the 2011 Census of Population for England and
      Wales. Using Census data in an innovative way under the new Office for National
      Statistics (ONS) Secure Research Service (SRS; previously the ONS Virtual
      Microdata Laboratory, VML), we investigate how bearers of a full range of given
      and family names assigned themselves to 2011 Census categories, using a names
      classification tool previously described in this journal. Based on these results,
      we develop a follow-up ethnicity estimation tool and describe how the tool may be
      used to observe changing relations between naming practices and ethnic identities
      as a facet of social integration and cosmopolitanism in an increasingly diverse
      society.

PMID- 30092009
TI  - Kinetics and perception of basketball landing in various heights and footwear
      cushioning.
AB  - BACKGROUND: The previous studies on basketball landing have not shown a
      systematic agreement between landing impacts and midsole densities. One plausible
      reason is that the midsole densities alone used to represent the cushioning
      capability of a shoe seems over simplified. The aim of this study is to examine
      the effects of different landing heights and shoes of different cushioning
      performance on tibial shock, impact loading and knee kinematics of basketball
      players. METHODS: Nineteen university team basketball players performed drop
      landings from different height conditions (0.45m vs. 0.61m) as well as with
      different shoe cushioning properties (regular, better vs. best-cushioned). For
      each condition, tibial acceleration, vertical ground reaction force and knee
      kinematics were measured with a tri-axial accelerometer, force plate and motion
      capture system, respectively. Heel comfort perception was indicated on the 150-mm
      Visual Analogue Scale. A 2 (height) x 3 (footwear) ANOVA with repeated measures
      was performed to determine the effects of different landing heights and shoe
      cushioning on the measured parameters. RESULTS: We did not find significant
      interactions between landing height and shoe conditions on tibial shock, impact
      peak, mean loading rate, maximum knee flexion angle and total ankle range of
      motion. However, greater tibial shock, impact peak, mean loading rates and total
      ankle range of motion were determined at a higher landing height (P < 0.01).
      Regular-cushioned shoes demonstrated significantly greater tibial shock and mean
      loading rate compared with better- and best-cushioned shoes (P < 0.05). The
      correlation analysis indicated that the heel comfort perception was fairly
      associated with impact peak and mean loading rate regardless of heights (P <
      0.05), but not associated with tibial shock. CONCLUSIONS: Determination of shoe
      cushioning performance, regardless of shoe midsole materials and constructions,
      would be capable in order to identify optimal shoe models for better protection
      against tibial stress fracture. Subjective comfort rating could estimate the
      level of impact loading in non-laboratory based situations.

PMID- 30092010
TI  - Overexpression of the rice gene OsSIZ1 in Arabidopsis improves drought-, heat-,
      and salt-tolerance simultaneously.
AB  - Sumoylation is one of the post translational modifications, which affects
      cellular processes in plants through conjugation of small ubiquitin like modifier
      (SUMO) to target substrate proteins. Response to various abiotic environmental
      stresses is one of the major cellular functions regulated by SUMO conjugation.
      SIZ1 is a SUMO E3 ligase, facilitating a vital step in the sumoylation pathway.
      In this report, it is demonstrated that over-expression of the rice gene OsSIZ1
      in Arabidopsis leads to increased tolerance to multiple abiotic stresses. For
      example, OsSIZ1-overexpressing plants exhibited enhanced tolerance to salt,
      drought, and heat stresses, and generated greater seed yields under a variety of
      stress conditions. Furthermore, OsSIZ1-overexpressing plants were able to exclude
      sodium ions more efficiently when grown in saline soils and accumulate higher
      potassium ions as compared to wild-type plants. Further analysis revealed that
      OsSIZ1-overexpressing plants expressed higher transcript levels of P5CS, a gene
      involved in the biosynthesis of proline, under both salt and drought stress
      conditions. Therefore, proline here is acting as an osmoprotectant to alleviate
      damages caused by drought and salt stresses. These results demonstrate that the
      rice gene OsSIZ1 has a great potential to be used for improving crop's tolerance
      to several abiotic stresses.

PMID- 30092011
TI  - Pancreatic cancer survival analysis defines a signature that predicts outcome.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer
      death in the US. Despite multiple large-scale genetic sequencing studies,
      identification of predictors of patient survival remains challenging. We
      performed a comprehensive assessment and integrative analysis of large-scale gene
      expression datasets, across multiple platforms, to enable discovery of a
      prognostic gene signature for patient survival in pancreatic cancer. PDAC RNA
      Sequencing data from The Cancer Genome Atlas was stratified into Survival+ (>2
      year survival) and Survival-(<1-year survival) cohorts (n = 47). Comparisons of
      RNA expression profiles between survival groups and normal pancreatic tissue
      expression data from the Gene Expression Omnibus generated an initial PDAC
      specific prognostic differential expression gene list. The candidate prognostic
      gene list was then trained on the Australian pancreatic cancer dataset from the
      ICGC database (n = 103), using iterative sampling based algorithms, to derive a
      gene signature predictive of patient survival. The gene signature was validated
      in 2 independent patient cohorts and against existing PDAC subtype
      classifications. We identified 707 candidate prognostic genes exhibiting
      differential expression in tumor versus normal tissue. A substantial fraction of
      these genes was also found to be differentially methylated between survival
      groups. From the candidate gene list, a 5-gene signature (ADM, ASPM, DCBLD2,
      E2F7, and KRT6A) was identified. Our signature demonstrated significant power to
      predict patient survival in two distinct patient cohorts and was independent of
      AJCC TNM staging. Cross-validation of our gene signature reported a better ROC
      AUC (>= 0.8) when compared to existing PDAC survival signatures. Furthermore,
      validation of our signature through immunohistochemical analysis of patient tumor
      tissue and existing gene expression subtyping data in PDAC, demonstrated a
      correlation to the presence of vascular invasion and the aggressive squamous
      tumor subtype. Assessment of these genes in patient biopsies could help further
      inform risk-stratification and treatment decisions in pancreatic cancer.

PMID- 30092012
TI  - Feasibility of implementing an outdoor walking break in Italian middle schools.
AB  - Brief bouts of physical activity during the school day are an innovative method
      for increasing physical activity in the school setting. The purpose of the study
      was to investigate if the introduction of an outdoor active break, based on
      walking and running, in a middle school in Italy is feasible in terms of
      implementation (i.e., adherence, costs, safety) and acceptability (i.e.,
      satisfaction, intent to continue use, perceived appropriateness). One hundred and
      forty students (aged 12 +/- 1 years) and 20 teachers (aged 50 +/- 8 years)
      participated in the activity for four months. The activity consisted of walking
      (or running) one kilometer outside the school buildings during the mid-morning.
      Data from questionnaires regarding the satisfaction with and the acceptability of
      the activity were collected. The activity was safely performed three to four days
      a week, without any costs to the school or to students' parents. Students and
      teachers were satisfied with the activity (positive answers from 95% and 89% of
      each group, respectively). Moreover, the teachers reported that the program was
      easy to organize and did not negatively influence their teaching activities. The
      intervention was easily and safely implemented, and it was considered suitable
      for the daily routine of an Italian middle school. Further studies are needed to
      examine its impact on physical activity levels and academic achievement.

PMID- 30092013
TI  - The peristomial plates of ophiuroids (Echinodermata: Ophiuroidea) highlight an
      incongruence between morphology and proposed phylogenies.
AB  - The peristomial plates are skeletal components of the interbrachial frame (or
      mouth frame), which is located below the true mouth of ophiuroids. Whilst the
      peristomial plates were extensively described and used as diagnostic characters
      by some early workers, for the past 100 years they have been largely neglected as
      a taxonomic resource. In this investigation the peristomial plates of 48 species
      representing 21 families were examined directly, and information on a further 61
      species, including representatives of another eight families, was obtained from
      the published literature. Observations were made with regard to fragmentation
      state, relative size and orientation of the peristomial plates. Although
      fragmentation state showed little consistency at any taxonomic level, relative
      size and orientation segregated a group of families comprising species with
      relatively small, inclined peristomial plates, viz. Ophiotrichidae,
      Ophiopholidae, Ophiactidae, Amphiuridae and Ophiocomidae, together with a single
      hemieuryalid species-Ophioplocus januarii. The distribution of peristomial plate
      traits was strongly correlated with that of several other character states
      pertaining to the interbrachial frame. This supported the proposition that two
      major types of interbrachial frame are present in ophiuroids (designated 'A' and
      'B'). Current phylogenies inferred from both morphological and molecular data
      imply that type B is derived and has evolved independently at least twice in the
      orders Amphilepidida and Ophiacanthida. This represents a remarkable example of
      evolutionary convergence. An analysis of the distribution of all interbrachial
      frame character states suggested that within the Amphilepidida paedomorphosis was
      probably responsible for the complete reversion of the interbrachial frame to the
      ancestral type A condition in two families (Ophiothamnidae and Amphilepididae) of
      suborder Gnathophiurina and possibly responsible for varying degrees of trait
      reversal in the four families of suborder Ophionereidina. Such paedomorphic
      events may have been associated with a secondary return to the deep-sea from
      shallow-sea environments.

PMID- 30092014
TI  - New ultrasound grading system for cesarean scar pregnancy and its implications
      for management strategies: An observational cohort study.
AB  - A cesarean section pregnancy (CSP) indicated the gestational sac (GS) implanted
      in the previous cesarean scar. The clinical manifestations of CSP present a wide
      range of variations, and the optimal management is yet to be defined. We
      retrospectively enrolled 109 patients with the diagnosis of CSP from our
      department and categorized them into four grades based on the ultrasound
      presentation. Grade I CSP indicated the GS embedded in less than one-half
      thickness of the lower anterior corpus; and grade II CSP represented the GS
      extended to more than one-half thickness of overlying myometrium. Grade III CSP
      implied the GS bulged out of the cesarean scar; and grade IV CSP denoted that GS
      became an amorphous tumor with rich vascularity at the cesarean scar. Seventy
      eight women received surgery, and the complication rate was 14.1% (11/78). Linear
      regression analysis demonstrated a significant association between the
      invasiveness of the surgery and their ultrasound gradings. The mainstream
      operation for grade I CSP was transcervical resection, while the majority of
      grade III and IV patients required hysterotomy or hysterectomy. Another 31 women
      received chemotherapy with methotrexate as their initial treatment. The success
      rate for chemotherapy was 61.3%; the remaining patients required further surgery
      due to persistent CSP or heavy bleeding during or after chemotherapy. Fifteen
      patients (48.3%) receiving chemotherapy suffered from complications (mostly
      bleeding). Among them, 7 (22.6%) patients experienced bleeding of more than 1,000
      mL, and 9 (29.0%) of these 31 patients required blood transfusions. Our novel
      ultrasound grading system for CSP may help to communicate between physicians, and
      determine the optimal surgical strategy. Chemotherapy with methotrexate for CSP
      is not satisfactory and is associated with a higher rate of complications.

PMID- 30092015
TI  - Correction: A framework for estimating society's economic welfare following the
      introduction of an animal disease: The case of Johne's disease.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198436.].

PMID- 30092017
TI  - Optimization of the standard genetic code according to three codon positions
      using an evolutionary algorithm.
AB  - Many biological systems are typically examined from the point of view of
      adaptation to certain conditions or requirements. One such system is the standard
      genetic code (SGC), which generally minimizes the cost of amino acid replacements
      resulting from mutations or mistranslations. However, no full consensus has been
      reached on the factors that caused the evolution of this feature. One of the
      hypotheses suggests that code optimality was directly selected as an advantage to
      preserve information about encoded proteins. An important feature that should be
      considered when studying the SGC is the different roles of the three codon
      positions. Therefore, we investigated the robustness of this code regarding the
      cost of amino acid replacements resulting from substitutions in these positions
      separately and the sum of these costs. We applied a modified evolutionary
      algorithm and included four models of the genetic code assuming various
      restrictions on its structure. The SGC was compared both with the codes that
      minimize the objective function and those that maximize it. This approach allowed
      us to place the SGC in the global space of possible codes, which is a more
      appropriate and unbiased comparison than that with randomly generated codes
      because they are characterized by relatively uniform amino acid assignments to
      codons. The SGC appeared to be well optimized at the global scale, but its
      individual positions were not fully optimized because there were codes that were
      optimized for only one codon position and simultaneously outperformed the SGC at
      the other positions. We also found that different code structures may lead to the
      same optimality and that random codes can show a tendency to minimize costs under
      some of the genetic code models. Our results suggest that the optimality of SGC
      could be a by-product of other processes.

PMID- 30092019
TI  - More legislation, more violence? The impact of Dodd-Frank in the DRC.
AB  - The Dodd Frank Act was passed by the US Congress in July 2010 and included a
      provision-Section 1502-that aimed to break the link between conflict and minerals
      in the Eastern Democratic Republic of Congo. To date there is only one rigorous
      quantitative analysis that investigates the impact of Dodd-Frank on local
      conflict events. Looking at the short-term impact (2011-2012), it finds that the
      policy backfired. This study builds on a larger, more representative, dataset of
      mining sites and extends the time horizon by three years (2013-2015). The results
      indicate that the policy also backfired in the longer run, especially in areas
      home to gold mines. For territories with the average number of gold mines, the
      introduction of Dodd-Frank increased the incidence of battles with 44%; looting
      with 51% and violence against civilians with 28%, compared to pre-Dodd Frank
      averages. Delving deeper into the impact of the conflict minerals legislation is
      important, as President Trump suspended the legislation in February 2017 for a
      two-year period, ordering his administration to replace it with another policy.

PMID- 30092018
TI  - Risk factors for retinal microvascular impairment in type 2 diabetic patients
      without diabetic retinopathy.
AB  - OBJECTIVES: To determine the risk factors for retinal microvascular impairment on
      optical coherence tomography angiography (OCT-A) in type 2 diabetic patients
      without clinical diabetic retinopathy (DR). METHODS: This retrospective and cross
      sectional study enrolled 74 diabetic patients without clinically evident DR for
      the study group and 34 healthy subjects for the control group. OCT-A parameters
      were measured to determine vascular density (VD) and the foveal avascular zone
      (FAZ) size in the superficial and deep capillary plexuses (SCP/DCP) of the
      retina. Clinical data were collected on sex, age, diabetes duration, hemoglobin
      A1c (HbA1c), hypertension, dyslipidemia, low-density lipoprotein cholesterol (LDL
      C), estimated glomerular filtration rate (eGFR) and smoking status. Multiple
      linear regression analyses were performed to represent the associated clinical
      variables with OCT-A parameters in diabetic patients. RESULTS: In comparison
      between the study and control groups, the VD in the SCP and DCP were
      significantly lower in diabetic patients compared to the controls (P = 0.022 and
      0.003, respectively). The FAZ size in the SCP and DCP were significantly greater
      in diabetic patients compared to the controls (P = 0.035 and <0.001,
      respectively). In age- and sex-adjusted multiple regression analyses for the
      diabetic patients, dyslipidemia and hypertension were negatively associated with
      SCP-VD (beta = -0.357, P = 0.002; beta = -0.239, P = 0.039, respectively).
      Current smoking was correlated with lower DCP-VD (beta = -0.255, P = 0.043).
      Greater SCP-FAZ size was associated with dyslipidemia and greater LDL-C (beta =
      0.254, P = 0.013; beta = 0.232, P = 0.029, respectively), and greater DCP-FAZ
      size, with lower eGFR and greater LDL-C (beta = -0.355, P = 0.004; beta = 0.235,
      P = 0.037, respectively). CONCLUSIONS: Diabetic patients without clinical DR
      showed lower VD and greater FAZ size in the SCP and DCP compared to healthy
      controls. In diabetic patients without clinical DR, dyslipidemia and/or high LDL
      C were important risk factors for retinal microvascular impairment. Hypertension,
      current smoking and lower eGFR also contributed to microvascular impairment.

PMID- 30092016
TI  - An original Eurasian haplotype, HLA-DRB1*14:54-DQB1*05:03, influences the
      susceptibility to idiopathic achalasia.
AB  - Idiopathic achalasia is a relatively infrequent esophageal motor disorder for
      which major histocompatibility complex (MHC) genes are well-identified risk
      factors. However, no information about HLA-achalasia susceptibility in Mexicans
      has previously been reported. We studied a group of 91 patients diagnosed with
      achalasia and 234 healthy controls with Mexican admixed ancestry. HLA alleles and
      conserved extended haplotypes were analyzed using high-resolution HLA typing
      based on Sanger and next-generation sequencing technologies. Admixture estimates
      were determined using HLA-B and short tandem repeats. Results were analyzed by
      non-parametric statistical analysis and Bonferroni correction. P-values < 0.05
      were considered significant. Patients with achalasia had 56.7% Native American
      genes, 24.7% European genes, 16.5% African genes and 2.0% Asian genes, which was
      comparable with the estimates in the controls. Significant increases in the
      frequencies of alleles DRB1*14:54 and DQB1*05:03 and the extended haplotypes
      DRB1*14:54-DQB1*05:03 and DRB1*11:01-DQB1*03:01, even after Bonferroni correction
      (pC<0.05), were found in the achalasia group compared to those in the controls.
      Concluding, the HLA class II alleles HLA-DRB1*14:54:01 and DQB1*05:03:01 and the
      extended haplotype are risk factors for achalasia in mixed-ancestry Mexican
      individuals. These results also suggest that the HLA-DRB1*14:54-DQB1*05:03
      haplotype was introduced by admixture with European and/or Asian populations.

PMID- 30092020
TI  - A combined planning approach for improved functional and esthetic outcome of
      bimaxillary rotation advancement for treatment of obstructive sleep apnea using
      3D biomechanical modeling.
AB  - In recent years, bimaxillary rotation advancement (BRA) has become the method of
      choice for surgical treatment of obstructive sleep apnea (OSA). As dislocation of
      the jaw bones affects both, airways and facial contours, surgeons are facing the
      challenge of finding an optimal jaw position that allows for the reestablishment
      of normal airway ventilation and esthetic surgical outcome. Owing to the
      complexity of the facial anatomy and its mechanical behavior, individual planning
      of surgical OSA treatment under consideration of functional and esthetic aspects
      presents a challenge that surgeons typically approach in a non-quantitative
      manner using subjective evaluation and clinical experience. This paper describes
      a framework for individual planning of OSA treatment using bimaxillary rotation
      advancement, which relies on computational modeling of hard and soft tissue
      mechanics. The described framework for simulation of functional and esthetic post
      surgery outcome was used in 10 OSA patients. Comparison of the simulation results
      with post-surgery data reveals that biomechanical simulation provides a reliable
      estimate for post-surgery facial tissue behavior and antero-posterior airway
      extension, but fails to accurately describe a surprisingly large lateral stretch
      of the velopharyngeal region. This discrepancy is traced back to anisotropic
      effects of pharyngeal muscles. Possible approaches to improving the accuracy of
      model predictions and defining sharp criteria for optimizing combined OSA
      planning are discussed.

PMID- 30092021
TI  - Correction: The combination of Cassia obtusifolia L. and Foeniculum vulgare M.
      exhibits a laxative effect on loperamide-induced constipation of rats.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0195624.].

PMID- 30092022
TI  - Is the priority review voucher program stimulating new drug development for
      tropical diseases?
AB  - Congress created the tropical disease priority review voucher program to
      stimulate new drug development for tropical diseases. An analysis of the
      pharmaceutical pipeline indicates that the development of drugs for these
      tropical diseases has increased. However, the effects of the program are not
      uniform across all diseases, as malaria and tuberculosis have seen significant
      new drug development, while other diseases have not.

PMID- 30092023
TI  - The antigenicity and cholesteroid nature of mycolic acids determined by
      recombinant chicken antibodies.
AB  - Mycolic acids (MA) are major, species-specific lipid components of Mycobacteria
      and related genera. In Mycobacterium tuberculosis, it is made up of alpha-,
      methoxy- and keto-MA, each with specific biological functions and conformational
      characteristics. Antibodies in tuberculosis (TB) patient sera respond differently
      towards the three MA classes and were reported to cross-react with cholesterol.
      To understand the antigenicity and cholesterol cross-reactivity of MA, we
      generated three different chicken -derived phage-displayed single-chain variable
      fragments (scFv) that reacted similarly towards the natural mixture of MA, but
      the first recognized all three classes of chemically synthetic MAs, the second
      only the two oxygenated types of MAs and the third only methoxy MA. The
      cholesterol cross-reactivity was investigated after grafting each of the three
      scFv types onto two configurations of constant chain domains-CH1-4 and CH2-4.
      Weak but significant cross-reactivity with cholesterol was found only with CH2-4
      versions, notably those two that were also able to recognize the trans-keto MA.
      The cholesteroid nature of mycobacterial mycolic acids therefore seems to be
      determined by the trans-keto MA subclass. The significantly weaker binding to
      cholesterol in comparison to MA confirms the potential TB diagnostic application
      of these antibodies.

PMID- 30092024
TI  - How to make hand hygiene interventions more attractive to nurses: A discrete
      choice experiment.
AB  - BACKGROUND: Better understanding of the characteristics of interventions which
      are attractive to nurses is required in order to implement effective hand hygiene
      interventions. METHODS: The intervention characteristics were derived from
      diffusion of innovation theory (DIT): relative advantage, compatibility,
      simplicity, trialability, and observability. To identify nurses' preferences for
      the five characteristics, a discrete choice experiment (DCE) was conducted.
      Participants were nurses working at Taiwanese tertiary care hospitals selected
      through stratified sampling. In addition, the hand hygiene moment (before or
      after patient contact) was taken into consideration in the DCE to investigate
      whether nurses' preferences for the intervention characteristics were the same at
      different hand hygiene moments. RESULTS: This survey was conducted between 1
      October and 31 December 2014. Among 200 nurses from three Taiwanese tertiary care
      hospitals, significant preferences for the five intervention characteristics were
      observed. That is, when an intervention makes the hand hygiene activity more
      convenient (p<0.001), when nurses participate in the design of the intervention
      (p<0.001), when an intervention is explained well to nurses before implementing
      it (p<0.001), when the evidence of hand hygiene is provided at a trial stage to
      show its effectiveness (p<0.001), and when nurses' hand hygiene performance is
      observable to their peers (p<0.001), nurses are more willing to wash their hands
      with high compliance. In addition, nurses preferred for providing evidence at a
      trial stage most, and well explanation about the intervention to increase
      simplicity was least. The rankings of the preference for the five intervention
      characteristics were the same at different hand hygiene moments (p = 0.453).
      CONCLUSIONS: The findings suggest policy directions for decision makers aiming to
      improve overall hand hygiene compliance in healthcare facilities.

PMID- 30092025
TI  - The topography of rods, cones and intrinsically photosensitive retinal ganglion
      cells in the retinas of a nocturnal (Micaelamys namaquensis) and a diurnal
      (Rhabdomys pumilio) rodent.
AB  - We used immunocytochemistry to determine the presence and topographical density
      distributions of rods, cones, and intrinsically photosensitive retinal ganglion
      cells (ipRGCs) in the four-striped field mouse (Rhabdomys pumilio) and the
      Namaqua rock mouse (Micaelamys namaquensis). Both species possessed duplex
      retinas that were rod dominated. In R. pumilio, the density of both cones and
      rods were high (cone to rod ratio: 1:1.23) and reflected the species'
      fundamentally diurnal, but largely crepuscular lifestyle. Similarly, the ratio of
      cones to rods in M. namaquensis (1:12.4) reflected its nocturnal lifestyle.
      Similar rod density peaks were observed (R. pumilio: ~84467/mm2; M. namaquensis:
      ~81088/mm2), but a density gradient yielded higher values in the central
      (~56618/mm2) rather than in the peripheral retinal region (~32689/mm2) in R.
      pumilio. Two separate cone types (S-cones and M/L-cones) were identified implying
      dichromatic color vision in the study species. In M. namaquensis, both cone
      populations showed a centro-peripheral density gradient and a consistent S- to
      M/L-cone ratio (~1:7.8). In R. pumilio, S cones showed a centro-peripheral
      gradient (S- to M/L-cone ratio; central: 1:7.8; peripheral: 1:6.8) which appeared
      to form a visual streak, and a specialized area of M/L-cones (S- to M/L-cone
      ratio: 1:15) was observed inferior to the optic nerve. The number of
      photoreceptors per linear degree of visual angle, estimated from peak
      photoreceptor densities and eye size, were four cones and 15 rods per degree in
      M. namaquensis and 11 cones and 12 rods per degree in R. pumilio. Thus, in
      nocturnal M. namaquensis rods provide much finer image sampling than cones,
      whereas in diurnal/crepuscular R. pumilio both photoreceptor types provide fine
      image sampling. IpRGCs were comparably sparse in R. pumilio (total = 1012) and M.
      namaquensis (total = 862), but were homogeneously distributed in M. namaquensis
      and densest in the dorso-nasal quadrant in R. pumilio. The adaptive significance
      of the latter needs further investigation.

PMID- 30092026
TI  - Why large seeds with physical dormancy become nondormant earlier than small ones.
AB  - Under natural conditions, large seeds with physical dormancy (PY) may become
      water permeable earlier than small ones. However, the mechanism for this
      difference has not been elucidated. Thus, our aim was to evaluate the traits
      associated with PY in seeds of Senna multijuga (Fabaceae) and to propose a
      mechanism for earlier dormancy-break in large than in small seeds. Two seedlots
      were collected and each separated into large and small seeds. Seed dry mass,
      water content, thickness of palisade layer in the hilar and distal regions and
      the ratio between palisade layer thickness (P) in the lens fissure and seed mass
      (M) were evaluated. Further, the correlation between seed mass and seed
      dimensions was investigated. Large seeds had higher dry mass and water content
      than small seeds. The absolute thickness of the palisade layer in the different
      regions did not show any trend with seed size; however, large seeds had a lower
      P:M ratio than small seeds. Seed mass correlated positively with all seed
      dimensions, providing evidence for a substantially higher volume in large seeds.
      Since wet, but not dry, high temperatures break PY in sensitive seeds of S.
      multijuga, the data support our prediction that internal pressure potential in
      the seed and palisade layer thickness in the water gap (lens), which is related
      to seed mass (i.e. P:M ratio), act together to modulate the second step (dormancy
      break) of the two-stage sensitivity cycling model for PY break. In which case,
      large seeds are predetermined to become water-permeable earlier than small ones.

PMID- 30092028
TI  - Reliability, validation and norms of the Chinese version of Anxiety Sensitivity
      Index 3 in a sample of military personnel.
AB  - This study aimed to explore the properties of the Chinese version of the Anxiety
      Sensitivity Index- 3 (ASI-3) in a sample of military personnel. Using non
      probabilistic sampling, the Chinese version of the ASI-3 was administered to
      3,077 valid participants aged 16 to 36 years old (M = 22.35, SD = 3.57) from nine
      military units. The Depression Anxiety Stress Scales-21 (DASS-21) and The State
      Trait Anxiety Inventory (STAI) were used to assess the construct validity. A one
      way analysis of variance was conducted to compare the differences in the services
      and positions of the participants. It was found that 1The indices of confirmatory
      factor analysis met the standard values, which supported the hypothesis of the
      three-factor model of the original ASI-3; 2ASI-3 was significantly associated
      with DASS-21 in positive ways, which indicated the high convergent validity; on
      the other hand, the correlation between ASI-3 and TAI was relatively low, which
      indicated there was an empirical discrimination between anxiety sensitivity and
      trait anxiety. 3The Cronbach's alpha coefficients were 0.926 for the total scale
      and 0.828-0.841 for the three subscales; 4At a cut-off score of 16, the
      sensitivity and specificity levels were 71.1% and 76.7%, respectively, where the
      sum of sensitivity and specificity becomes the maximum, accompanied with
      improvement of PPV and NPV; 5There were significant findings in the ASI and
      subscales among the five services and four positions. This study provides new
      evidence that the Chinese version of the Anxiety Sensitivity Index-3 has good
      validity and reliability and could be applied as an effective tool to assess
      anxiety sensitivity in military personnel. Our recommendations to researchers and
      practitioners are that the three factor model should be replicated across some
      different special forces and the items and constructs could be modified on
      Chinese culture.

PMID- 30092027
TI  - Biomarker panels for characterizing microbial community biofilm formation as
      composite molecular process.
AB  - Microbial consortia execute collaborative molecular processes with contributions
      from individual species, on such basis enabling optimized molecular function.
      Such collaboration and synergies benefit metabolic flux specifically in extreme
      environmental conditions as seen in acid mine drainage, with biofilms as relevant
      microenvironment. However, knowledge about community species composition is not
      sufficient for deducing presence and efficiency of composite molecular function.
      For this task molecular resolution of the consortium interactome is to be
      retrieved, with molecular biomarkers particularly suited for characterizing
      composite molecular processes involved in biofilm formation and maintenance. A
      microbial species set identified in 18 copper environmental sites provides a data
      matrix for deriving a cross-species molecular process model of biofilm formation
      composed of 191 protein coding genes contributed from 25 microbial species.
      Computing degree and stress centrality of biofilm molecular process nodes allows
      selection of network hubs and central connectors, with the top ranking molecular
      features proposed as biomarker candidates for characterizing biofilm homeostasis.
      Functional classes represented in the biomarker panel include quorum sensing,
      chemotaxis, motility and extracellular polysaccharide biosynthesis, complemented
      by chaperones. Abundance of biomarker candidates identified in experimental data
      sets monitoring different biofilm conditions provides evidence for the selected
      biomarkers as sensitive and specific molecular process proxies for capturing
      biofilm microenvironments. Topological criteria of process networks covering an
      aggregate function of interest support the selection of biomarker candidates
      independent of specific community species composition. Such panels promise
      efficient screening of environmental samples for presence of microbial community
      composite molecular function.

PMID- 30092029
TI  - Blockade of dengue virus entry into myeloid cells by endocytic inhibitors in the
      presence or absence of antibodies.
AB  - BACKGROUND: Dengue is the most prevalent arthropod-borne viral human disease in
      tropical and subtropical regions, caused by four dengue virus (DENV) serotypes.
      In spite of the increasing global incidence, no specific antiviral therapy is
      available. Cells of the mononuclear phagocyte lineage are the main targets either
      for direct antibody (Ab)-independent or Ab-mediated human DENV infection, usually
      associated to the severe forms of disease. Since the virus entry may be a
      convenient therapeutic alternative, this study aimed to investigate the mode of
      DENV internalization into myeloid cells in the absence and presence of DENV Ab
      and evaluate the inhibitory activity of diverse biochemical inhibitors of
      endocytosis. METHODOLOGY/PRINCIPAL FINDINGS: By infectivity assays and
      quantitative RT-PCR determinations, it was demonstrated that DENV-2 entry into
      U937 and K562 cells in the absence of Ab was highly inhibited by the early
      treatment with ammonium chloride, chlorpromazine and dynasore, but it was not
      affected by methyl-beta-cyclodextrin, indicating that DENV-2 utilizes a low pH
      dependent, clathrin- and dynamin-mediated endocytic infectious pathway for the
      direct entry into both human myeloid cells. To study the Ab-mediated entry of
      DENV, the experimental conditions for enhancement of infection were established
      by inoculating immune complexes formed with DENV-2 and the Ab 2H2 or 3H5. The
      internalization of DENV-2-2H2 or DENV-2-3H5 complexes in both myeloid cells was
      also dependent on acid pH and dynamin but a differential requirement of the
      clathrin-mediated endocytic route was observed depending on the FcgammaR involved
      in the complex uptake: the infection through FcgammaRII was dependent on clathrin
      coated vesicles whereas the internalization pathway mediated by FcgammaRI was
      independent of clathrin. This property was not serotype-specific.
      CONCLUSIONS/SIGNIFICANCE: DENV entry into myeloid cells in the absence or
      presence of Ab can be blocked by diverse biochemical inhibitors affecting the
      cellular factors involved in endocytosis. The identification of the virus-host
      interactions involved in virus penetration may allow the finding of host-targeted
      antivirals widely active against diverse pathogenic flaviviruses with similar
      requirements for virus entry.

PMID- 30092030
TI  - SURGE complex of Plasmodium falciparum in the rhoptry-neck (SURFIN4.2-RON4-GLURP)
      contributes to merozoite invasion.
AB  - Plasmodium falciparum invasion into red blood cells (RBCs) is a complex process
      engaging proteins on the merozoite surface and those contained and sequentially
      released from the apical organelles (micronemes and rhoptries). Fundamental to
      invasion is the formation of a moving junction (MJ), a region of close apposition
      of the merozoite and the RBC plasma membranes, through which the merozoite draws
      itself before settling into a newly formed parasitophorous vacuole (PV).
      SURFIN4.2 was identified at the surface of the parasitized RBCs (pRBCs) but was
      also found apically associated with the merozoite. Using antibodies against the N
      terminus of the protein we show the presence of SURFIN4.2 in the neck of the
      rhoptries, its secretion into the PV and shedding into the culture supernatant
      upon schizont rupture. Using immunoprecipitation followed by mass spectrometry we
      describe here a novel protein complex we have named SURGE where SURFIN4.2 forms
      interacts with the rhoptry neck protein 4 (RON4) and the Glutamate Rich Protein
      (GLURP). The N-terminal cysteine-rich-domain (CRD) of SURFIN4.2 mediates binding
      to the RBC membrane and its interaction with RON4 suggests its involvement in the
      contact between the merozoite apex and the RBC at the MJ. Supporting this
      suggestion, we also found that polyclonal antibodies to the extracellular domain
      (including the CRD) of SURFIN4.2 partially inhibit merozoite invasion. We propose
      that the formation of the SURGE complex participates in the establishment of
      parasite infection within the PV and the RBCs.

PMID- 30092031
TI  - Distinct amino acid motifs carrying multiple positive charges regulate membrane
      targeting of dysferlin and MG53.
AB  - Dysferlin (Dysf) and mitsugumin53 (MG53) are two key proteins involved in
      membrane repair of muscle cells which are efficiently recruited to the sarcolemma
      upon lesioning. Plasma membrane localization and recruitment of a Dysf fragment
      to membrane lesions in zebrafish myofibers relies on the presence of a short,
      polybasic amino acid motif, WRRFK. Here we show that the positive charges carried
      by this motif are responsible for this function. In mouse MG53, we have
      identified a similar motif with multiple basic residues, WKKMFR. A single amino
      acid replacement, K279A, leads to severe aggregation of MG53 in inclusion bodies
      in HeLa cells. This result is due to the loss of positive charge, as shown by
      studying the effects of other neutral amino acids at position 279. Consequently,
      our data suggest that positively charged amino acid stretches play an essential
      role in the localization and function of Dysf and MG53.

PMID- 30092032
TI  - Correction: Nutritional Iron Deficiency Anemia: Magnitude and Its Predictors
      among School Age Children, Southwest Ethiopia: A Community Based Cross-Sectional
      Study.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0114059.].

PMID- 30092034
TI  - The effects of time frames on self-report.
AB  - BACKGROUND: The degree to which episodic and semantic memory processes contribute
      to retrospective self-reports have been shown to depend on the length of
      reporting period. Robinson and Clore (2002) argued that when the amount of
      accessible detail decreases due to longer reporting periods, an episodic
      retrieval strategy is abandoned in favor of a semantic retrieval strategy. The
      current study further examines this shift between retrieval strategies by
      conceptually replicating the model of Robinson and Clore (2002) for both emotions
      and symptoms and by attempting to estimate the exact moment of the theorized
      shift. METHOD: A sample of 469 adults reported the extent to which they
      experienced 8 states (excited, happy, calm, sad, anxious, angry, pain, stress)
      over 12 time frames (right now to in general). A series of curvilinear and
      piecewise linear multilevel growth models were used to examine the pattern of
      response times and response levels (i.e., rated intensity on a 1-5 scale) across
      the different time frames. RESULTS: Replicating previous results, both response
      times and response levels increased with longer time frames. In contrast to prior
      work, no consistent evidence was found for a change in response patterns that
      would suggest a shift in retrieval strategies (i.e., a flattening or decrease of
      the slope for longer time frames). The relationship between the time frames and
      response times/levels was similar for emotions and symptoms. CONCLUSIONS:
      Although the current study showed a pronounced effect of time frame on response
      times and response levels, it did not replicate prior work that suggested a shift
      from episodic to semantic memory as time frame duration increased. This indicates
      that even for longer time frames individuals might attempt to retrieve episodic
      information to provide a response. We suggest that studies relying on self-report
      should use the same well-defined time frames across all self-reported measures.

PMID- 30092033
TI  - Accelerated magnetic resonance fingerprinting using soft-weighted key-hole (MRF
      SOHO).
AB  - OBJECT: To develop a novel approach for highly accelerated Magnetic Resonance
      Fingerprinting (MRF) acquisition. MATERIALS AND METHODS: The proposed method
      combines parallel imaging, soft-gating and key-hole approaches to highly
      accelerate MRF acquisition. Slowly varying flip angles (FA), commonly used during
      MRF acquisition, lead to a smooth change in the signal contrast of consecutive
      time-point images. This assumption enables sharing of high frequency data between
      different time-points, similar to what is done in some dynamic MR imaging methods
      such as key-hole. The proposed approach exploits this information using a SOft
      weighted key-HOle (MRF-SOHO) reconstruction to achieve high acceleration factors
      and/or increased resolution without compromising image quality or increasing scan
      time. MRF-SOHO was validated on a standard T1/T2 phantom and in in-vivo brain
      acquisitions reconstructing T1, T2 and proton density parametric maps. RESULTS:
      Accelerated MRF-SOHO using less data per time-point and less time-point images
      enabled a considerable reduction in scan time (up to 4.6x), while obtaining
      similar T1 and T2 accuracy and precision when compared to zero-filled MRF
      reconstruction. For the same number of spokes and time-points, the proposed
      method yielded an enhanced performance in quantifying parameters than the zero
      filled MRF reconstruction, which was verified with 2, 1 and 0.7 (sub-millimetre)
      resolutions. CONCLUSION: The proposed MRF-SOHO enabled a 4.6x scan time reduction
      for an in-plane spatial resolution of 2x2 mm2 when compared to zero-filled MRF
      and enabled sub-millimetric (0.7x0.7 mm2) resolution MRF.

PMID- 30092035
TI  - The need for information among patients with hematological malignancies:
      Psychometric analyses of the 62-item Hematology Information Needs Questionnaire
      (HINQ-62).
AB  - The purpose of this study was to investigate the psychometric characteristics
      (content validity, internal consistency, and subscale structure) of the
      Hematology Information Needs Questionnaire-62 (HINQ-62), a patient reported
      outcome measure (PROM) for assessing the need for information among patients with
      hematological malignancies (HM-patients). Baseline data were used from a
      prospective study on the need for information which 336 newly diagnosed HM
      patients had completed. In phase 1 (design phase), data from the first 135
      patients were used and in phase 2 (validation phase), data from the remaining 201
      HM patients were used. Content validity was analyzed by examining irrelevance of
      items. Items were considered irrelevant if more than 10% of the patients scored
      totally disagree on that item. The subscale structure of the HINQ-62 was
      investigated with Factor analysis (FA) (exploratory FA in phase 1 and
      confirmatory FA in phase 2). Cronbach's alpha was computed for the different
      subscales and >.70 was considered as good internal consistency. None of the 62
      HINQ-items were irrelevant. Exploratory FA identified five subscales: "Disease,
      symptoms, treatment and side-effects", "Etiology, sleep and physical changes",
      "Self-care", "Medical tests and prognosis", and "Psychosocial". Root Mean Square
      Error of Approximation (RMSEA) among patients was 0.037 in phase 1 and 0.045 in
      phase 2. The comparative fit index (CFI)/Tucker-Lewis index -non-normed fit index
      among patients was 0.984/0.983 and 0.948/0.946, in phase 1 and 2 respectively.
      The internal consistency of the subscales was good, with Cronbach's alpha 0.82
      0.99. The HINQ is a valid PROM for assessing the need for information among Dutch
      HM-patients at diagnosis.

PMID- 30092036
TI  - Two-minute walk test: Reference equations for healthy adults in China.
AB  - BACKGROUND AND OBJECTIVE: Although the six-minute walk test (6MWT) is widely used
      as a measure of exercise capacity, it may not be applicable in some settings and
      populations. This issue has led to increased use of the two-minute walk test
      (2MWT) to assess exercise capacity. The main objective of this study is to
      establish reference equations for the two-minute walk distance (2MWD) in healthy
      Chinese adults aged 18-85 years. METHODS: A total of 973 volunteers took part in
      the study. We obtained verbal consent from all participants before the test, and
      the study design was approved by the ethics committees of Wenzhou People's
      Hospital. The participants performed two 2MWTs using a standardized protocol, and
      the longer distance was used for further analysis. Stepwise multiple regression
      analysis was performed using age, height and weight as independent variables and
      was used to establish the reference equations for the 2MWD in the male and female
      groups. RESULTS: The mean walking distance for all participants was 199.1+/-25.81
      m. Age and height were identified as independent factors that influenced the
      2MWD, and they explained 35% and 34% of the variance in distance for the male and
      female groups, respectively. CONCLUSION: This study resulted in determination of
      reference equations for predicting the 2MWD in healthy Chinese adults. These 2MWD
      standards will provide useful references for medical care in some settings and
      populations.

PMID- 30092037
TI  - Evaluating the impact of social support services on tuberculosis treatment
      default in Ukraine.
AB  - Ukraine is among the top 20 highest drug-resistant tuberculosis burden countries
      in the world. Driving the high drug-resistant tuberculosis rates is an unchecked
      treatment default rate. This evaluation measures the effect of social support
      provided to tuberculosis patients at risk of defaulting on treatment during
      outpatient treatment. Five tuberculosis patient cohorts, served in three oblasts
      from 2011 and 2012, were constructed from medical records to compare risk factors
      for default, receipt of social services, and treatment outcome. Regression
      analyses were used to identify risk factors predictive of treatment default and
      to estimate the impact of the social support program on treatment default,
      controlling for risk, disease status, and demographics. In 2012, tuberculosis
      patients receiving social support in Ukraine reduced their probability of
      defaulting on continuation treatment by 10 percentage points compared to high
      risk patients who did not receive social support in 2012 or 2011. Treatment
      success rates for the high-risk patients receiving social support were comparable
      to the low-risk cohorts and significantly improved over the high-risk comparison
      cohorts. Further research is recommended to quantify the costs and benefits for
      scaling-up social support services, evaluate social support program fidelity,
      identify which populations respond best to select services, and what barriers
      might still exist to achieve better adherence. With that information, tailoring
      programs to most effectively reach and serve clients in a patient-centered
      approach may reap substantial rewards for Ukraine.

PMID- 30092038
TI  - Foraging behavior and locomotion of the invasive Argentine ant from winter
      aggregations.
AB  - The collective behavior of ant colonies, and locomotion of individuals within a
      colony, both respond to changing conditions. The invasive Argentine ant
      (Linepithema humile) thrives in Mediterranean climates with hot, dry summers and
      colder, wet winters. However, its foraging behavior and locomotion has rarely
      been studied in the winter. We examined how the foraging behavior of three
      distinct L. humile colonies was related to environmental conditions and the
      locomotion of workers during winter in northern California. We found that
      colonies foraged most between 10 and 15 degrees C, regardless of the maximum
      daily temperature. Worker walking speed was positively associated with
      temperature (range 6-24 degrees C) and negatively associated with humidity (range
      25-93%RH). All colonies foraged during all day and night hours in a predictable
      daily cycle, with a correlation between the rate of incoming and outgoing
      foragers. Foraging activity was unrelated to the activity of a competing native
      ant species, Prenolepis imparis, which was present in low abundance, and ceased
      only during heavy rain when ants left foraging trails and aggregated in small
      sheltered areas on trees.

PMID- 30092039
TI  - Correction: Anxiety and the severity of Tension-Type Headache mediate the
      relation between headache presenteeism and workers' productivity.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201189.].

PMID- 30092040
TI  - Correction: Simple reaction times to cyclopean stimuli reveal that the binocular
      system is tuned to react faster to near than to far objects.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0188895.].

PMID- 30092041
TI  - Aedes albopictus production in urban stormwater catch basins and manhole chambers
      of downtown Shanghai, China.
AB  - BACKGROUND: The near-surface urban drainage system in Shanghai is highly complex,
      with hundreds of thousands of catch basins (CBs) and manhole chambers (MCs).
      Comparatively little is known about the breeding of mosquitoes in this vast
      system, especially for the locally predominant species Aedes albopictus. A cross
      sectional mosquito sampling study was conducted from late July to early August of
      2017 using 539 CBs and 309 MCs located in 10 communities of downtown Shanghai. We
      measured the water-holding status of the drainage systems and density of mosquito
      larvae. Mosquito species were examined on site and in the laboratory later.
      RESULTS: The CBs were characterized by a lower percentage of standing water
      compared to MCs (47.0% vs. 79.9%, respectively; X2 = 76.407, P<0.001), but CBs
      contained a higher percentage of stagnant water percent than MCs (45.2% vs.
      35.3%, respectively; X2 = 11.465, P = 0.001). There were exclusively two species
      of mosquito larvae found in the drainage systems, Ae. albopictus and Culex
      pipiens complex. Compared with MCs, the structures of CBs were more conducive to
      larval production and yielded more larvae-positive samples (43.4% vs 14.2%, X2 =
      53.136, P<0.001) and higher larval density (8.23 vs. 4.09 per dipper, t = 3.287,
      P = 0.001). Aedes albopictus was the predominant species in CBs, with a
      constituent ratio of 71.7%. Regarding structures with different features in
      different locations, CBs that had a vertical grate with an unsealed lid and MCs
      with plastic composite covers were the most favorable types for mosquito
      breeding, and residential neighborhoods yielded the highest number of Ae.
      albopictus. CONCLUSION: Aedes albopictus was the predominant species in both CBs
      and stormwater MCs, especially in residential neighborhoods. CBs, particularly
      those with vertical grates, were a major source of mosquito production in
      downtown Shanghai. MCs featured more running water and fewer larvae by
      percentage, and few larvae were found in Sewage MCs. However, due to the
      tremendous baseline amount, MCs were still an important breeding source of
      mosquitoes. We suggest that Aedes control in Shanghai should focus on CBs or
      other potential larvae habitats in and around residential neighborhoods. The use
      of permeable materials and completely sealed covers should be adopted in the
      construction of CBs and MCs henceforth.

PMID- 30092042
TI  - The neurofilament derived-peptide NFL-TBS.40-63 enters in-vitro in human neural
      stem cells and increases their differentiation.
AB  - Regenerative medicine is a promising approach to treat neurodegenerative diseases
      by replacing degenerating cells like neurons or oligodendrocytes. Targeting human
      neural stem cells directly in the brain is a big challenge in such a strategy.
      The neurofilament derived NFL-TBS.40-63 peptide has recently been introduced as a
      novel tool to target neural stem cells. Previous studies showed that this peptide
      can be internalized by rat neural stem cells in vitro and in vivo, which
      coincided with lower proliferation and self-renewal capacity and increase of
      differentiation. In this study, we analyzed the uptake and potential effects of
      the NFL-TBS.40-63 peptide on human neural stem cells isolated from human fetuses.
      We showed that the peptide inhibits proliferation and the ability to produce
      neurospheres in vitro, which is consistent with an increase in cell adhesion and
      differentiation. These results confirm that the peptide could be a promising
      molecule to target and manipulate human neural stem cells and thus could serve as
      a strategic tool for regenerative medicine.

PMID- 30092043
TI  - The current malaria morbidity and mortality in different transmission settings in
      Western Kenya.
AB  - BACKGROUND: Passive surveillance of malaria in health facilities remains vital
      for implementation of control and elimination programs. It is therefore essential
      understanding current age profile of clinical malaria morbidity, mortality and
      presentations in areas with variant infection susceptibility. This study aimed at
      understanding the current malaria morbidity and mortality in Western Kenya.
      METHODS: Surveillance of clinical and asymptomatic parasitological positivity
      rates of all malaria suspected patients and school children were respectively
      determined from June 2015 to August 2016. From 2014 to 2016, register books in
      hospitals were referred and the confirmed malaria cases in conjunction with total
      number of monthly outpatient visits (OPD) counted. All registered malaria
      admissions were counted together with other causes of admissions. Moreover,
      outcome of malaria admissions in terms of discharge or death was recorded using
      inpatient charts within the same time frame. Prospective surveillance of severe
      malaria collected information on clinical features of the disease. Giemsa stained
      blood slides confirmed existence of malaria parasitemia. Chi-square and analysis
      of variance tests were used, respectively, to compute proportions and means; then
      a comparison was made between different age groups, periods, and study areas.
      RESULTS: During the survey of asymptomatic infections among school children,
      overall blood slide positivity ranged from 6.4% at the epidemic prone site to
      38.3% at the hyperendemic site. During the clinical malaria survey, school age
      children (5-14) presented with overall the highest (45%) blood slide positivity
      rate among those suspected to have the infection at the epidemic prone study
      site. The survey of all malaria confirmed and registered cases at OPD found 17%
      to 27% of all consultations among <5 children and 9.9% to 20.7% of all OPD visits
      among the >=5 patients were due to malaria. Moreover, survey of all registered
      causes of admission in hospitals found 47% of admissions were due to malaria. The
      disease was a major cause of admission in epidemic prone setting where 63.4% of
      the <5 children and 62.8% of the >=5 patients were admitted due to malaria
      (p>0.05) and 40% of all malaria admissions were school age children. Malaria
      related death rate was highest among <5 years at the hyperendemic site, that is
      60.9 death per 1000 malaria <5 admissions. Conversely, the epidemic prone setting
      experienced highest malaria related death among >=15 years (18.6 death per 1000
      admissions) than the < 15 years (5.7 death per 1000 admissions of the <15 years)
      (p< 0.001). Surveillance of severe form of the disease found that hyperpyrexia,
      hyperparastemia, prostration and convulsions as common presentations of severe
      disease. CONCLUSION: Malaria is still the major cause of hospital consultations
      in Western Kenya with an alarming number of severe forms of the disease among the
      school aged children at the epidemic prone setting. Mortalities were higher among
      <5 children years in high infection transmission setting and among >=15 years in
      low and moderate transmission settings. Surveillance of asymptomatic and
      symptomatic malaria along with evaluation of current interventions in different
      age groups should be implemented in Kenya.

PMID- 30092044
TI  - Correction: AIM2 Drives Joint Inflammation in a Self-DNA Triggered Model of
      Chronic Polyarthritis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0131702.].

PMID- 30092045
TI  - Correction: A reassessment of the early archaeological record at Leang Burung 2,
      a Late Pleistocene rock-shelter site on the Indonesian island of Sulawesi.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0193025.].

PMID- 30092046
TI  - Trend analysis for national surveys: Application to all variables from the
      Canadian Health Measures Survey cycle 1 to 4.
AB  - BACKGROUND: Trend analysis summarizes patterns over time in the data to show the
      direction of change and can be used to investigate uncertainties in different
      time points and associations with other factors. However, this approach is not
      widely applied to national surveys and only selected outcomes are investigated.
      This study demonstrates a research framework to conduct trend analysis for all
      variables in a national survey, the Canadian Health Measures Survey (CHMS). DATA
      AND METHODS: The CHMS cycle 1 to 4 was implemented between 2007 and 2015. The
      characteristics of all variables were screened and associated to the weight
      variables. Missing values were identified and cleaned according to the User
      Guide. The characteristics of all variables were extracted and used to guide data
      cleaning. Trend analysis examined the statistical significance of candidate
      predictors: the cycles, age, sex, education, household income and body mass index
      (BMI). R (v3.2) and RStudio (v0.98.113) were used to develop the framework.
      RESULTS: There were 26557 variables in 79 data files from four cycles. There were
      1055 variables significantly associated with the CHMS cycles and 2154 associated
      with the BMI after controlling for other predictors. The trend of blood pressure
      was similar to those published. CONCLUSION: Trend analysis for all variables in
      the CHMS is feasible and is a systematic approach to understand the data. Because
      of trend analysis, we have detected data errors and identified several
      environmental biomarkers with extreme rates of change across cycles. The impact
      of these biomarkers has not been well studied by Statistics Canada or others.
      This framework can be extended to other surveys, especially the Canadian
      Community Health Survey.

PMID- 30092048
TI  - Correction: Earliest evidence for equid bit wear in the ancient Near East: The
      "ass" from Early Bronze Age Tell es-Safi/Gath, Israel.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0196335.].

PMID- 30092047
TI  - Functional characterization of unique enzymes in Xanthomonas euvesicatoria
      related to degradation of arabinofurano-oligosaccharides on hydroxyproline-rich
      glycoproteins.
AB  - In this study, we clarified the functions of three uncharacterized enzymes,
      XCV2724, XCV2728, and XCV2729, in Xanthomonas euvesicatoria, the causal agent of
      bacterial spot of tomato and pepper. The genes corresponding to the three enzymes
      are homologs of hypBA1, hypBA2, and hypAA from Bifidobacterium longum and are
      unique to Xanthomonas spp. among plant pathogenic bacteria. Functional
      characterization of the recombinant enzymes expressed using microbial systems
      revealed that they degrade the arabinofurano-oligosaccharides present on
      hydroxyproline (Hyp)-rich glycoproteins (HRGPs) such as extensin and solanaceous
      lectins in plant cell walls. These enzymes work coordinately to degrade the
      oligosaccharides. First, XeHypAA (XCV2728), belonging to the glycoside hydrolase
      (GH) 43 family, releases L-arabinose from L-arabinofuranose (Araf)-alpha1,3-Araf
      beta1,2-Araf-beta1,2-Araf-beta-Hyp (Ara4-Hyp), cleaving its alpha1,3 bond;
      second, XeHypBA2 (XCV2729), belonging to the GH121 family, releases the
      disaccharide Araf-beta1,2-Araf from Araf-beta1,2-Araf-beta1,2-Araf-beta-Hyp (Ara3
      Hyp); finally, XeHypBA1 (XCV2724), belonging to GH family 127, releases L
      arabinose from Araf-beta-Hyp (Ara-Hyp). In summary, the main oligosaccharide
      structure of Ara4-Hyp on the HRGPs is degraded to Ara3-Hyp, then to Ara-Hyp, and
      finally to Ara monosaccharides by the action of these three enzymes. HRGPs
      containing oligosaccharide substrates have been reported to contribute to plant
      defense, and interestingly, the promoter region of the operon (xehypBA2 and
      xehypAA) contains the plant-inducible promoter box for binding the regulator
      protein HrpX involved in pathogenicity. We then analyzed the expression level of
      the operon gene in hrp-inducing medium and in plants and constructed gene
      deletion mutants. However, although the operon was evidently upregulated by HrpX,
      three single-gene deletion mutants (DeltaxehypBA1, DeltaxehypBA2, DeltaxehypAA)
      and even a triple-gene deletion mutant (DeltaxehypBA1-BA2-AA) remained
      pathogenic, and had no effect on nonhost resistance, either, indicating that
      these three enzymes are not involved in either pathogenicity or nonhost
      resistance reactions. This is the first report of enzymes in plant pathogenic
      bacteria that catalyze the degradation of Hyp-linked-L-arabinofuranosides in
      plant cell walls.

PMID- 30092049
TI  - Metagenomic analysis of rhizosphere microflora of oil-contaminated soil planted
      with barley and alfalfa.
AB  - The role of rhizosphere microbial communities in the degradation of hydrocarbons
      remains poorly understood and is a field of active study. We used high throughput
      sequencing to explore the rhizosphere microbial diversity in the alfalfa and
      barley planted oil contaminated soil samples. The analysis of 16s rRNA sequences
      showed Proteobacteria to be the most enriched (45.9%) followed by Bacteriodetes
      (21.4%) and Actinobacteria (10.4%) phyla. The results also indicated differences
      in the microbial diversity among the oil contaminated planted soil samples. The
      oil contaminated planted soil samples showed a higher richness in the microbial
      flora when compared to that of untreated samples, as indicated by the Chao1
      indices. However, the trend was different for the diversity measure, where oil
      contaminated barley planted soil samples showed slightly lower diversity indices.
      While the clustering of soil samples grouped the oil contaminated samples within
      and across the plant types, the clean sandy soil samples formed a separate group.
      The oil contaminated rhizosphere soil showed an enrichment of known oil-degrading
      genera, such as Alcanivorax and Aequorivita, later being specifically enriched in
      the contaminated soil samples planted with barley. Overall, we found a few well
      known oil-degrading bacterial groups to be enriched in the oil contaminated
      planted soil samples compared to the untreated samples. Further, phyla such as
      Thermi and Gemmatimonadetes showed an enrichment in the oil contaminated soil
      samples, indicating their potential role in hydrocarbon degradation. The findings
      of the current study will be useful in understanding the rhizosphere microflora
      responsible for oil degradation and thus can help in designing appropriate
      phytoremediation strategies for oil contaminated lands.

PMID- 30092050
TI  - Life cycle adapted upstream open reading frames (uORFs) in Trypanosoma
      congolense: A post-transcriptional approach to accurate gene regulation.
AB  - The presented work explores the regulatory influence of upstream open reading
      frames (uORFs) on gene expression in Trypanosoma congolense. More than 31,000
      uORFs in total were identified and characterized here. We found evidence for the
      uORFs' appearance in the transcriptome to be correlated with proteomic expression
      data, clearly indicating their repressive potential in T. congolense, which has
      to rely on post-transcriptional gene expression regulation due to its unique
      genomic organization. Our data show that uORF's translation repressive potential
      does not only correlate with elemental sequence features such as length, position
      and quantity, but involves more subtle components, in particular the codon and
      amino acid profiles. This corresponds with the popular mechanistic model of a
      ribosome shedding initiation factors during the translation of a uORF, which can
      prevent reinitiation at the downstream start codon of the actual protein-coding
      sequence, due to the former extensive consumption of crucial translation
      components. We suggest that uORFs with uncommon codon and amino acid usage can
      slow down the translation elongation process in T. congolense, systematically
      deplete the limited factors, and restrict downstream reinitiation, setting up a
      bottleneck for subsequent translation of the protein-coding sequence.
      Additionally we conclude that uORFs dynamically influence the T. congolense life
      cycle. We found evidence that transition to epimastigote form could be supported
      by gain of uORFs due to alternative trans-splicing, which down-regulate
      housekeeping genes' expression and render the trypanosome in a metabolically
      reduced state of endurance.

PMID- 30092051
TI  - Immunosuppressive protocols with tacrolimus after cryopreserved aortal
      allotransplantation in rats.
AB  - OBJECTIVES AND DESIGN: The aim of our study was to simulate in rats all aspects
      and techniques used in our new clinical program of cryopreserved alloarterial
      transplantation and investigate the influence of two immunosuppressive protocols
      with tacrolimus on acute rejection of these allografts. MATERIALS AND METHODS:
      Cryopreserved abdominal aortic grafts were transplanted between Brown-Norway and
      Lewis rats. Tacrolimus (0.2 mg/kg daily) was administered from day 1 to day 30
      (TAC1) or from day 7 to day 30 (TAC7), respectively. No immunosuppressed
      isogeneic (ISO) and allogeneic (ALO) rats combination served as control. Aortal
      wall infiltration by immunocompetent cells (MHC II+ cells of recipient origin)
      was studied on day 30 after transplantation. Flow cytometry was used for the
      analysis of day 30 sera for the presence of donor specific anti-MHC class I and
      II antibodies. RESULTS: The aortal allografts in both immunosuppressed groups
      showed regular morphology of aortal wall with no depositions of immunoglobulin G
      on day 30. The adventitial infiltration of non-immunosuppressed aortal allografts
      by MHC class II positive cells of recipient origin was significantly higher (ALO
      20.7+/-6.7 cells, P<0.001) compared to both immunosuppressed groups (TAC1 5.9+/
      5.5 cells, TAC7 6.1+/-5.1 cells). Day 30 sera from the allogeneic non
      immunosuppressed animals decreased significantly the binding of fluorescence
      labelled MHC class I (46.9+/-19.4%) and class II (65.8+/-11.9%) antibody to
      donors spleen cells compared with day 30 sera from both immunosuppressed groups
      (TAC1, anti-MHC class I 102.4+/-4.2%, p < 0.001, anti-MHC class II 102.6+/-6.0%),
      (TAC7, anti-MHC class I 79.9+/-3.3%, p < 0.001, anti-MHC class II 80.9+/-2.7%).
      CONCLUSION: Both immunosuppressed protocols with tacrolimus (administration from
      day 1 or from day 7 following transplantation) were able to suppress acute cell-
      and antibody-mediated rejection of cryopreserved abdominal aortic allografts
      processed in accordance with our new standardized clinical protocol.

PMID- 30092053
TI  - Correction: 2'-O-methylation of the mRNA cap protects RNAs from decapping and
      degradation by DXO.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0193804.].

PMID- 30092052
TI  - Exercise training improves vascular function and secondary health measures in
      survivors of pediatric oncology related cerebral insult.
AB  - Adolescent and young adult (AYA) survivors of pediatric oncology related cerebral
      insult are vulnerable to numerous treatment-induced deficits that significantly
      enhance cardiovascular disease risk. Regular exercise improves endothelial
      function, fitness, body composition and musculoskeletal function which may reduce
      predisposition for cardiovascular disease. Here we assessed the feasibility and
      effectiveness of a 24-week exercise intervention on cardiovascular, physical and
      metabolic outcomes in this population. Thirteen survivors (6 male, 7 female;
      median age 19 y (range 16-23 y) were recruited to participate in a 48-week study
      consisting of a 24-week control period (regular care) followed by a 24-week
      exercise intervention. Outcome measures were collected at entry (week 0) and
      following regular care (24-week) and exercise (48-week). Assessed variables
      included endothelial function (flow mediated dilation, FMD), blood pressure,
      heart rate (HR), aerobic capacity, anthropometry, body composition, muscular
      strength (3 repetition maximum testing), muscular endurance (repetitions/min) and
      physical activity levels (accelerometry). Compared to baseline, delta diameter (p
      = 0.008) and FMD (p = 0.029) of the brachial artery increased following exercise.
      Bicep-curl strength also increased following exercise compared to baseline (p =
      0.019), while submaximal (6 min mark) measures of ventilation (p = 0.012), rating
      of perceived exertion (p = 0.012), HR (p = 0.001), absolute (p = 0.000) and
      relative (p = 0.000) aerobic capacity decreased. Breaks in sedentary time
      increased (p = 0.043) following exercise compared to regular care. Although the
      sample was small and heterogeneous, this study demonstrates that exercise is
      achievable and has positive effects on vascular function, submaximal fitness,
      local strength and physical activity in a population of AYA survivors of
      pediatric oncology related cerebral insult.

PMID- 30092055
TI  - Retraction: The effects of residual platelets in plasma on plasminogen activator
      inhibitor-1 and plasminogen activator inhibitor-1-related assays.

PMID- 30092054
TI  - Calcimimetic R-568 vasodilatory effect on mesenteric vascular beds from
      normotensive (WKY) and spontaneously hypertensive (SHR) rats. Potential
      involvement of vascular smooth muscle cells (vSMCs).
AB  - The potential role of calcimimetics as vasculotropic agents has been suggested
      since the discovery that calcium sensing receptors (CaSRs) are expressed in
      cardiovascular tissues. However, whether this effect is CaSR-dependent or 
      independent is still unclear. In the present study the vascular activity of
      calcimimetic R-568 was investigated in mesenteric vascular beds (MVBs) isolated
      from Spontaneously Hypertensive rats (SHR) and the relative age-matched Wistar
      Kyoto (WKY) control rats. Pre-constricted MBVs were perfused with increasing
      concentrations of R-568 (10 nM- 30 MUM) resulting in a rapid dose-dependent
      vasodilatation. However, in MVBs from SHR this was preceded by a small but
      significant vasoconstriction at lowest nanomolar concentrations used (10-300 nM).
      Pre-treatment with pharmacological inhibitors of nitric oxide (NO) synthase (NOS,
      L-NAME), KCa channels (CTX), cyclo-oxygenase (INDO) and CaSR (Calhex) or the
      endothelium removal suggest that NO, CaSR and the endothelium itself contribute
      to the R-568 vasodilatory/vasoconstrictor effects observed respectively in
      WKY/SHR MVBs. Conversely, the vasodilatory effects resulted by highest R-568
      concentration were independent of these factors. Then, the ability of lower R-568
      doses (0.1-1 MUM) to activate endothelial-NOS (eNOS) pathway in MVBs homogenates
      was evaluated. The Akt and eNOS phosphorylation levels resulted increased in WKY
      homogenates and Calhex significantly blocked this effect. Notably, this did not
      occur in the SHR. Similarly, vascular smooth muscle cells (vSMCs) stimulation
      with lower R-568 doses resulted in Akt activation and increased NO production in
      WKY but not in SHR cells. Interestingly, in these cells this was associated with
      the absence of the biologically active dimeric form of the CaSR thus potentially
      contributing to explain the impaired vasorelaxant effect observed in response to
      R-568 in MVB from SHR compared to WKY. Overall, these findings provide new
      insight on the mechanisms of action of the calcimimetic R-568 in modulating
      vascular tone both in physiological and pathological conditions such as
      hypertension.

PMID- 30092056
TI  - "We might get a lot more families who will agree": Muslim and Jewish perspectives
      on less invasive perinatal and paediatric autopsy.
AB  - BACKGROUND: Perinatal and paediatric autopsy rates are at historically low levels
      with declining uptake due to dislike of the invasiveness of the procedure, and
      religious objections particularly amongst Muslim and Jewish parents. Less
      invasive methods of autopsy including imaging with and without tissue sampling
      have been shown to be feasible alternatives. We sought to investigate attitudes
      including religious permissibility and potential uptake amongst members of the
      Muslim and Jewish communities in the United Kingdom. METHODS: Semi-structured
      interviews with religious and faith-based authorities (n = 16) and bereaved
      parents from the Jewish community (n = 3) as well as 10 focus groups with
      community members (60 Muslim participants and 16 Jewish participants) were
      conducted. Data were analysed using thematic analysis to identify key themes.
      FINDINGS: Muslim and Jewish religious and faith-based authorities agreed that non
      invasive autopsy with imaging was religiously permissible because it did not
      require incisions or interference with the body. A minimally invasive approach
      was less acceptable as it still required incisions to the body, although in those
      circumstances where it was required by law it was more acceptable than a full
      autopsy. During focus group discussions with community members, the majority of
      participants indicated they would potentially consent to a non-invasive autopsy
      if the body could be returned for burial within 24 hours, or if a family had
      experienced multiple fetal/pregnancy losses and the information gained might be
      useful in future pregnancies. Minimally invasive autopsy was less acceptable but
      around half of participants might consent if a non-invasive autopsy was not
      suitable, with the exception of the Jewish Haredi community who unanimously
      stated they would decline this alternative. CONCLUSIONS: Our research suggests
      less invasive autopsy offers a viable alternative to many Muslim and Jewish
      parents in the UK who currently decline a full autopsy. The findings may be of
      importance to other countries with significant Muslim and/or Jewish communities
      as well as to other religious communities where concerns around autopsy exist.
      Awareness-raising amongst religious leaders and community members will be
      important if these methods become routinely available.

PMID- 30092057
TI  - Genome wide association mapping of agro-morphological traits among a diverse
      collection of finger millet (Eleusine coracana L.) genotypes using SNP markers.
AB  - Finger millet (Eleusine coracana L.) is an important dry-land cereal in Asia and
      Africa because of its ability to provide assured harvest under extreme dry
      conditions and excellent nutritional properties. However, the genetic improvement
      of the crop is lacking in the absence of suitable genomic resources for reliable
      genotype-phenotype associations. Keeping this in view, a diverse global finger
      millet germplasm collection of 113 accessions was evaluated for 14 agro
      morphological characters in two environments viz. ICAR-Vivekananda Institute of
      Hill Agriculture, Almora (E1) and Crop Research Centre (CRC), GBPUA&T, Pantnagar
      (E2), India. Principal component analysis and cluster analysis of phenotypic data
      separated the Indian and exotic accessions into two separate groups. Previously
      generated SNPs through genotyping by sequencing (GBS) were used for association
      mapping to identify reliable marker(s) linked to grain yield and its component
      traits. The marker trait associations were determined using single locus single
      trait (SLST), multi-locus mixed model (MLMM) and multi-trait mixed model (MTMM)
      approaches. SLST led to the identification of 20 marker-trait associations (MTAs)
      (p value<0.01 and <0.001) for 5 traits. While advanced models, MLMM and MTMM
      resulted in additional 36 and 53 MTAs, respectively. Nine MTAs were common out of
      total 109 associations in all the three mapping approaches (SLST, MLMM and MTMM).
      Among these nine SNPs, five SNP sequences showed homology to candidate genes of
      Oryza sativa (Rice) and Setaria italica (Foxtail millet), which play an important
      role in flowering, maturity and grain yield. In addition, 67 and 14 epistatic
      interactions were identified for 10 and 7 traits at E1 and E2 locations,
      respectively. Hence, the 109 novel SNPs associated with important agro
      morphological traits, reported for the first time in this study could be
      precisely utilized in finger millet genetic improvement after validation.

PMID- 30092058
TI  - Low linolenic and linoleic acid consumption are associated with chronic kidney
      disease in patients with type 2 diabetes.
AB  - AIM: This cross-sectional study aimed to assess the association of the fat
      content in the diet with Diabetic Kidney Disease (DKD) in patients with type 2
      diabetes. METHODOLOGY: Patients from the Diabetes research clinic at Hospital de
      Clinicas de Porto Alegre (Brazil) were consecutively recruited. The inclusion
      criterion was the diagnosis of type 2 diabetes. The exclusion criteria were as
      follows: body mass index >40 kg/m2, heart failure, gastroparesis, diabetic
      diarrhea, dietary counseling by a registered dietitian during the previous 12
      months, and inability to perform the weighed diet records (WDR). The dietary
      fatty acids (saturated, monounsaturated and polyunsaturated) consumption was
      estimated by 3-day WDR. Compliance with the WDR technique was assessed by
      comparison of protein intake estimated from the 3-day WDR and from the 24-h
      urinary nitrogen output performed on the third day of the WDR period. The
      presence of DKD was defined as urinary albumin excretion (UAE) >= 30 mg / 24 h
      or/and glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. Urinary albumin was
      measured twice and eGFR was estimated by using the CKD-EPI equation. RESULTS: A
      total of 366 patients were evaluated; of these, 33% (n = 121) had DKD.
      Multivariate analysis showed that the intake of linolenic acid was negatively
      associated with DKD (OR = 0.57; 95% CI 0.35-0.93; P = 0.024), adjusted for
      gender, smoking, cardiovascular disease, ACE inhibitors and/or angiotensin
      receptor blocker use, systolic blood pressure, fasting plasma glucose and HDL
      cholesterol. In a separate model, similar results were observed for linoleic
      acid, adjusting to the same co-variables (OR = 0.95; 95% CI 0.91-0.99; P =
      0.006). CONCLUSION: The lower intake of polyunsaturated fatty acids, especially
      linolenic and linoleic acid, is associated with chronic kidney disease in
      patients with type 2 diabetes.

PMID- 30092059
TI  - Patients with cystic echinococcosis in the three national referral centers of
      Mongolia: A model for CE management assessment.
AB  - BACKGROUND: Mongolia is one of the endemic countries for cystic echinococcosis
      (CE), a zoonotic disease caused by the larval stage of Echinococcus granulosus.
      The goal of this study is to describe the current clinical management of CE in
      Mongolia, to capture the distribution of cyst stages of patients treated, and to
      contrast current practice with WHO-IWGE expert consensus. METHODS: Hospital
      records of CE patients treated between 2008 and 2015 at the three state hospitals
      and fulfilling the inclusion criterion 'discharge diagnosis CE' (ICD 10 code
      B.67.0-67.9) were reviewed. Demographical, geographical, clinical and
      ultrasonography (US) data were extracted and analyzed. The annual surgical
      incidence was estimated. The digital copies of US cyst images were independently
      staged by three international experts following the WHO CE cyst classification to
      determine the proportions of patients which ideally would have been assigned to
      the WHO recommended treatment modalities surgery, percutaneous, medical
      (benzimidazole) treatment and watch & wait. RESULTS: A total of 290 patient
      records fulfilled the inclusion criteria of the study. 45.7% of patients were
      below 15 years of age. 73.7% of CE cysts were located in abdominal organs,
      predominantly liver. US images of 84 patients were staged and assessed for
      interrater-agreement. The average raw agreement was 77.2%. Unweighted Kappa
      coefficient and weighted Kappa was 0.57 and 0.59, respectively. Mean proportions
      of images judged as stages CE1, CE2, CE3a, CE3b, CE4 and CL were 0.59, 0.01,
      0.19, 0.08, 0.03 and 0.11, respectively. 40 cysts met the inclusion criteria of
      treatment modality analysis. The mean proportions of cases with a single cyst
      assigned to medical, percutaneous treatment, surgery and watch & wait were 52.5%
      (95% CI 42-65), 25.8% (95% CI 15-30), 5.1% (95% CI 0-10) and 3.3% (95% CI 0-10),
      respectively. 13.3% (95% CI 5-25) of cysts were staged as CL and therefore
      assigned to further diagnostic requirement. CONCLUSION: WHO CE cyst
      classification and WHO-IWGE expert consensus on clinical CE management is not
      implemented in Mongolia. This results in exclusively surgical treatment, an
      unnecessary high risk approach for the majority of patients who could receive
      medical, percutaneous treatment or observation (watch & wait). Introduction of
      WHO-IWGE expert consensus and training in ultrasound CE cyst staging would be
      highly beneficial for patients and the health care services.

PMID- 30092061
TI  - Correction: Social reference managers and their users: A survey of demographics
      and ideologies.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198033.].

PMID- 30092060
TI  - H7 Hemagglutinin nanoparticles retain immunogenicity after >3 months of 25
      degrees C storage.
AB  - Vaccine distribution infrastructure remains inadequate in many parts of the
      world, and it is estimated that up to 40-50% of all vaccine doses are wasted in
      certain countries. Vaccines that can maintain viability outside of the cold chain
      would decrease vaccine wastage and increase immunization rates in regions of the
      world with underdeveloped vaccine distribution infrastructure. We examined the
      potential of crosslinked protein nanoparticles, made from trimerized influenza
      hemagglutinin (3HA), to maintain immunogenicity after cold-chain-independent
      storage. We found that the nanoparticles could be stored for 112 days at room
      temperature without any loss in hemagglutinating activity or immunogenicity, and
      that nanoparticles could be stored at 37 degrees C for 2 weeks without any loss
      in hemagglutinating activity. As vaccine development moves towards the use of
      recombinant subunit antigens, our results demonstrate the potential of
      crosslinked antigen nanoparticles as an immunogenic vehicle for bringing
      effective vaccines to underdeveloped regions outside of the cold chain.

PMID- 30092062
TI  - Is human life worth peanuts? Risk attitude changes in accordance with varying
      stakes.
AB  - Risk aversion is well-known as a general and robust characteristic of people's
      decision making: people are less likely to gamble when they are unsure if they
      will obtain the expected value of the bet made. The "peanuts effect" is, however,
      an exception to this general rule. The "peanuts effect," which states that people
      are more willing to gamble when playing for "peanuts" (a small outcome), has been
      stably observed in the context of a small monetary stake. We conducted two types
      of experiments to verify whether the peanuts effect still occurred when the type
      of stakes changed. We had two main findings. On the one hand, people tended to
      gamble more for a qualitatively smaller value when the stake was material in
      nature, meaning that the "peanuts effect" occurred with a qualitatively low
      stake. On the other hand, people were willing to take a risk for a qualitatively
      larger value when the stake was a human life: this is the opposite phenomenon of
      the "peanuts effect."

PMID- 30092063
TI  - Correction: Spiroplasma infection in Harmonia axyridis - Diversity and multiple
      infection.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198190.].

PMID- 30092064
TI  - What are the determinants for individuals to undergo cardiovascular disease
      health checks? A cross sectional survey.
AB  - BACKGROUND: There is a need to improve public's participation in health checks
      for early identification of individuals at high risk of CVD for prevention. The
      objective of this study is to identify significant determinants associated with
      individuals' intention to undergo CVD health checks. These determinants could be
      used to develop effective strategies to improve CVD health check participation.
      METHODS: This was a cross sectional survey using mall intercept interviews. It
      was carried out in a hypermarket surrounded by housing estates with a population
      of varying socioeconomic backgrounds. Inclusion criteria were Malaysian
      nationality and age 30 years and older. The validated CVD health check
      questionnaire was used to assess participants' intention and the determinants
      that influenced their intention to undergo CVD health checks. RESULTS: A total of
      413 participants were recruited. The median age of the participants was 45 years
      (IQR 17 years) and 60% of them were female. Participants indicated they were
      likely (45.0%) or very likely (38.7%) to undergo CVD health checks while 16.2%
      were not sure, unlikely or very unlikely to undergo health checks. Using ordinal
      regression analysis, perception of benefits, drawbacks of CVD health checks,
      perception of external barriers and readiness to handle outcomes following CVD
      health checks were the significant determinants of individuals' intention to
      undergo CVD health checks. CONCLUSIONS: To improve individuals' participation in
      CVD health checks, we need to develop strategies to address their perception of
      benefits and drawbacks of CVD health checks, the perceived external barriers and
      their readiness to handle outcomes following CVD health checks.

PMID- 30092065
TI  - A positive attitude towards provision of end-of-life care may protect against
      burnout: Burnout and religion in a super-aging society.
AB  - AIM: The aim of our study was to investigate factors associated with burnout of
      nurses and care workers in nursing homes and geriatric hospitals in Japan. The
      use of Buddhist priests, the major religion in Japan, was also explored. METHODS:
      Questionnaires for nurses and care workers were sent to 10 care facilities. The
      survey questions included basic demographic information, the Japanese Burnout
      Index and the Japanese version of the Frommelt Attitude Toward Care Of Dying
      Scale Form B. They also asked questions about use of Buddhist priests for tasks
      such as helping to manage the anxiety or distress of patients, families, and
      staff, or providing sutra chanting. RESULTS: In total, 323 questionnaires were
      returned, of which 260 were used for analysis. Only 18 (6.9%) answered that they
      had any religious beliefs, which was relatively low compared to 27% from
      governmental survey data. In total, however, 71% expressed a need for Buddhist
      priests to help with anxiety or distress among patients. A positive attitude
      towards providing end-of-life care was a protective factor against
      depersonalization. It was, however, also related to lower feelings of personal
      accomplishment. CONCLUSION: Care homes and geriatric hospitals may want to
      consider calling more on religious resources as a support for staff and patients.

PMID- 30092067
TI  - Comparison between optical coherence tomography angiography and immunolabeling
      for evaluation of laser-induced choroidal neovascularization.
AB  - This study aimed to investigate the differences between images obtained by
      optical coherence tomography angiography (OCTA) with those from
      immunohistochemical labeling of laser-induced choroidal neovascularization (CNV)
      in a mouse model. CNV was induced by laser photocoagulation (GYC-2000, NIDEK;
      wavelength 532 nm) in the left eyes of 10 female C57BL/6J mice aged 6 weeks. The
      laser parameters included a 100-MUm spot, 100-ms pulse duration and 200-mW
      incident power to rupture Bruch's membrane. OCT and OCTA CNV images were obtained
      using the RS-3000 Advance (NIDEK) 5 days post-laser photocoagulation. After OCTA
      imaging, the isolated choroid/retinal pigment epithelium complexes were
      fluorescently labeled with CD31 (an endothelial cell marker), platelet-derived
      growth factor receptor beta (PDGFRbeta, a pericyte-like scaffold marker), alpha
      smooth muscle actin (alpha-SMA) and collagen I. Area measurements of the lesions
      obtained by enface OCTA were compared with immunolabeled CD31+ CNV lesions in
      choroid flat-mounts. We also examined structural correlations between the
      PDGFRbeta+ pericyte-like scaffold and OCTA images. Laser-induced CNV was clearly
      detected by enface OCTA, appearing as a hyperflow lesion surrounded by a dark
      halo. Area measurements of the CNV lesion by immunolabeling were significantly
      larger than those obtained by enface OCTA (p = 0.006). The CNV lesion beneath the
      periphery of the pericyte-like scaffold was not clearly visible by enface OCTA
      due to the dark halo; however, the lesion was detectable as blood flow by cross
      sectional OCTA and was also highly labeled by CD31. The periphery of the pericyte
      like scaffold appeared to develop into subretinal fibrosis and this region was
      rich in myofibroblasts. Enface OCTA was unable to detect the entire area of laser
      induced CNV in mice, with an undetectable portion located beneath the fibrotic
      periphery of the pericyte-like scaffold. Due to this OCTA fibrosis artifact, OCTA
      imaging has limited potential for accurately estimating CNV lesions.

PMID- 30092069
TI  - Retraction: Functional Role of mTORC2 versus Integrin-Linked Kinase in Mediating
      Ser473-Akt Phosphorylation in PTEN-Negative Prostate and Breast Cancer Cell
      Lines.

PMID- 30092068
TI  - Multilevel analysis of personality, family, and classroom influences on emotional
      and behavioral problems among Chinese adolescent students.
AB  - BACKGROUND: The classroom environment plays a potentially important role in
      shaping the emotions and behavior of adolescents. However, few studies have
      focused on this factor. The aim of this study was to explore the association
      between the classroom environment and emotional and behavioral problems among
      Chinese adolescents while also considering personality-and family-related
      factors. METHODS: This cross-sectional study was conducted in November and
      December, 2009. A set of questionnaires, including the Strengths and Difficulties
      Questionnaire (SDQ), the Eysenck Personality Questionnaire (EPQ), the Family
      Environment Scale (FES), the Questionnaire on Teacher Interaction (QTI), and the
      Center for Epidemiological Studies- Depression Scale (CES-D), were distributed to
      participants. A total of 5,433 Chinese adolescent students (aged 9-18) and 244
      classroom teachers in Liaoning Province were ultimately included in the study.
      Hierarchical linear modeling was used to explore the factors associated with
      emotional and behavioral problems. RESULTS: Multilevel analyses revealed that
      adolescent emotional and behavioral problems significantly varied among
      classrooms. Although personality and family characteristics exerted the greatest
      influence on adolescents' emotions and behavior at the individual-level,
      interactions between classroom teachers and students increasingly affected
      adolescents with respect to age at the class-level. A mild positive association
      was found between adolescents' mental health problems and the mental health of
      teachers. CONCLUSION: This study focused on the classroom environment in order to
      understand Chinese adolescent mental health problems, the findings of which
      highlight important implications for policymakers and educators. The results
      underscore the importance of establishing a comfortable classroom climate by
      improving teacher-student interactions and meeting specific needs at different
      school stages, thus promoting a climate of positive mental health among Chinese
      adolescents.

PMID- 30092066
TI  - Serum concentrations of interleukin 18 and 25-hydroxyvitamin D3 correlate with
      depression severity in men with psoriasis.
AB  - OBJECTIVE: Psoriasis and depression may have common mechanisms, such as systemic
      inflammation, dysfunction of the hypothalamic-pituitary-adrenal axis, and vitamin
      D3 deficiency. Among men with psoriasis, this study examined whether depression
      severity was associated with serum concentrations of different metabolic and
      inflammatory markers. METHODS: The study included 85 men with psoriasis (mean age
      +/- standard deviation [SD], 47 +/- 14 years) and 65 men without psoriasis (mean
      age +/- SD, 44 +/- 13 years). In both groups, we measured the body mass index;
      blood pressure; and serum concentrations of lipids, uric acid, lipase,
      interleukins 6 and 18, cortisol, and 25-hydroxyvitamin D3. All participants
      completed the Beck Depression Inventory. Other variables analyzed included
      psoriasis duration, the Psoriasis Area Severity Index, and the percentage of body
      surface area affected by psoriatic lesions. RESULTS: Compared with controls,
      patients with psoriasis had significantly greater depression severity, higher
      body mass indices, and higher serum concentrations of total cholesterol and
      interleukins 6 and 18; moreover, they had significantly lower serum 25
      hydroxyvitamin D3 concentrations. In patients with psoriasis, depression severity
      correlated positively with psoriasis duration, the Psoriasis Area Severity Index,
      the percentage of body surface area affected by psoriatic lesions, and
      interleukin-18 concentration. In patients with psoriasis, depression severity
      correlated negatively with 25-hydroxyvitamin D3 concentration, but it did not
      correlate significantly with the serum concentrations of interleukin 6 and
      cortisol. CONCLUSIONS: High concentrations of interleukin 18 and low
      concentrations of 25-hydroxyvitamin D3 may be associated with depression severity
      in men with psoriasis. Thus, further studies should examine whether effective
      anti-inflammatory treatments or vitamin D3 supplementation can improve depression
      outcomes in these patients.

PMID- 30092070
TI  - Early stop of progesterone supplementation after confirmation of pregnancy in
      IVF/ICSI fresh embryo transfer cycles of poor responders does not affect
      pregnancy outcome.
AB  - Previous studies indicated that progesterone can be withdrawn at the time of the
      first positive beta-hCG test without compromising the clinical pregnancy outcome
      in normal ovarian responder. However, the effect of early stop of progesterone
      supplementation for patients with poor ovarian response (POR) has not been
      investigated. This study retrospectively collected data from patients with POR in
      156 IVF/ICSI fresh embryo transfer (ET) cycles in single tertiary center from
      January 2010 to June 2016. All the patients met ESHRE consensus, the Bologna
      criteria, of POR and had hCG injection for luteal phase support (LPS) on day 2, 5
      and 8 after ovum pick-up. The pregnant patients were divided into two groups:
      early stop group represented those who stopped LPS from day of positive pregnancy
      test; control group represented those who kept progesterone supplementation till
      gestational age of 9 weeks. There were no significant differences in age, BMI,
      parity, hormone data, number of follicles>10(mm), endometrial thickness and
      number of embryos transferred between the two groups. After adjustment for
      possible confounders with multivariate logistic regression analysis, the clinical
      pregnancy rates (55.0% vs. 57.1%, P = 0.35), ongoing pregnancy rates (47.0% vs.
      46.4%, P = 0.66), miscarriage rates (34.0% vs. 26.7%, P = 0.66) and live-birth
      rates (44.0% vs. 46.4%, P = 0.41) were not statistically different between early
      stop group and the control group. Our study indicates that early stop of
      progesterone supplementation on the day of positive pregnancy test for patients
      of POR using hCG as LPS in fresh ET cycles does not affect pregnancy outcome.

PMID- 30092071
TI  - Characterization of intra- and inter-host norovirus P2 genetic variability in
      linked individuals by amplicon sequencing.
AB  - Noroviruses are the main cause of epidemics of acute gastroenteritis at a global
      scale. Although chronically infected immunocompromised individuals are regarded
      as potential reservoirs for the emergence of new viral variants, viral
      quasispecies distribution and evolution patterns in acute symptomatic and
      asymptomatic infections has not been extensively studied. Amplicons of 450 nts
      from the P2 coding capsid domain were studied using next-generation sequencing
      (454/GS-Junior) platform. Inter-host diversity between symptomatic and
      asymptomatic acutely infected individuals linked to the same outbreak as well as
      their viral intra-host diversity over time were characterized. With an average of
      2848 reads per sample and a cutoff frequency of 0.1%, minor variant haplotypes
      were detected in 5 out of 8 specimens. Transmitted variants could not be
      confirmed in all infected individuals in one outbreak. The observed initial intra
      host viral diversity in asymptomatically infected subjects was higher than in
      symptomatic ones. Viral quasispecies evolution over time within individuals was
      host-specific, with an average of 2.8 nt changes per day (0.0062 changes per
      nucleotide per day) in a given symptomatic case. Nucleotide polymorphisms were
      detected in 28 out of 450 analyzed nucleotide positions, 32.14% of which were
      synonymous and 67.86% were non-synonymous. Most observed amino acid changes
      emerged at or near blockade epitopes A, B, D and E. Our results suggest that
      acutely infected individuals, even in the absence of symptoms, which go
      underreported and may enhance transmission, may contribute to norovirus genetic
      variability and evolution.

PMID- 30092072
TI  - Trends of HIV incidence and prevalence among men who have sex with men in
      Beijing, China: Nine consecutive cross-sectional surveys, 2008-2016.
AB  - BACKGROUND: Sexual transmission of HIV among men who have sex with men (MSM)
      increased markedly in China during the past decade. HIV incidence is a critical
      indicator in HIV surveillance and we use a HIV-1 BED-capture-enzyme immunoassay
      (BED-CEIA) to examine the incidence among MSM in Beijing from 2008 to 2016. Risk
      factors related to recent HIV infection were also assessed. METHODS: Consecutive
      cross-sectional surveys on MSM were conducted yearly from 2008 through 2016.
      Demographic and behaviors data were collected. HIV status was determined and HIV
      positive specimens were tested for recent infection using BED-CEIA. Specimens
      with ODn values<=0.8 were considered recently infected, HIV incidence rates and
      prevalence were then calculated. Risk factors associated with recent HIV
      infection were assessed by univariate and multivariable logistic regression.
      RESULTS: From 2008 to 2016, the numbers of eligible participants in the nine
      consecutive years ranged from 472 to 616. All the 261 eligible HIV-positive
      specimens were subjected to recent HIV infection testing. HIV prevalence ranged
      from 5.0% (3.3%-6.8%) to 10.2% (7.8%-12.7%), and incidence ranged from 1.57%
      (0.19%-2.95%) to 6.63% (3.65%-9.61%). MSM who never or sometimes used condoms
      during anal sex with men in the past 6 months (aOR = 1.515, 95%CI: 1.016-2.257, p
      = 0.041), or having syphilis infection (aOR = 1.561, 95%CI: 0.946-2.575, p =
      0.081) were more likely to be recently infected with HIV. Being a Beijing
      resident (aOR = 0.409, 95%CI: 0.212-0.790, p = 0.008), or having only one male
      anal sex partner in the past 6 months (aOR = 0.467, 95%CI: 0.220-0.994, p =
      0.048) were associated with a lower risk for recent HIV infection. CONCLUSIONS:
      The HIV incidence fluctuated among MSM in Beijing. Unprotected anal sex, having
      multiple sex partners, being a non-registered Beijing resident and having a
      syphilis infection play important roles in the recent HIV infection. Effective
      intervention measures for HIV and syphilis control and prevention should be
      continuously strengthened.

PMID- 30092073
TI  - Economic burden of caregiving for persons with severe mental illness in sub
      Saharan Africa: A systematic review.
AB  - BACKGROUND: Over the past two decades, the focus of mental health care has
      shifted from institutionalisation to community-based programs and short hospital
      stays. This change means that there is an increased role for caregivers, mostly
      family members, in managing persons with mental illness. Although there is
      evidence to support the benefits of deinstitutionalisation of mental health care,
      there are also indications of substantial burden experienced by caregivers; the
      evidence of which is limited in sub-Saharan Africa. However, knowledge of the
      nature and extent of this burden can inform the planning of mental health
      services that will not only benefit patients, but also caregivers and households.
      OBJECTIVE: To systematically review the available evidence on the economic burden
      of severe mental illness on primary family caregivers in sub-Saharan Africa.
      METHODS: A comprehensive search was conducted in Pubmed, CINAHL, Econlit and Web
      of Science with no date limitations up to September 2016 using keywords such as
      "burden", "cost of illness" and "economic burden" to identify relevant published
      literature. Articles were appraised using a standardised data extraction tool
      covering themes such as physical, psychological and socioeconomic burden.
      RESULTS: Seven papers were included in the review. Caregivers were mostly family
      members with a mean age of 46.34, female and unemployed. Five out of seven
      studies (71%) estimated the full economic burden of severe mental illness on
      caregivers. The remainder of studies just described the caregiver burden. All
      seven papers reported moderate to severe caregiver burden characterised by
      financial constraint, productivity loss and lost employment. The caregiver's
      level of income and employment status, severity of patient's condition and
      duration of mental illness were reported to negatively affect the economic burden
      experienced by caregivers. CONCLUSION: There is paucity of studies reporting the
      burden of severe mental illness on caregivers in sub-Saharan Africa. Further
      research is needed to present the nature and extent of this burden to inform
      service planning and policymaking.

PMID- 30092075
TI  - Correction: Diagnostic role of 18F-FDG PET/MRI in patients with gynecological
      malignancies of the pelvis: A systematic review and meta-analysis.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0175401.].

PMID- 30092076
TI  - Is mobile app a new political discussion platform? An empirical study of the
      effect of WeChat use on college students' political discussion and political
      efficacy.
AB  - In the last couple of years, the increasing application and popularization of
      mobile app have dramatically transformed people's daily political lives through
      offering innovative mechanisms for interpersonal communication. While a majority
      of past studies on WeChat have mainly focused on its characteristics, only few
      documents have unearthed the potential effect of using such emerging social media
      on facilitating political discussion and increasing political efficacy. Given
      those, this study adopted uses and gratifications approach to explore the
      possible relationships between gratifications-sought, the intensity of WeChat
      usage on mobile phones, online political discussion, and political efficacy among
      college students in China. An empirical survey with 282 WeChat users reveals that
      WeChat as a relatively new outlet of political information, which fosters online
      political discussion with others about government and politics. Contrary to the
      expectation, the intensity of WeChat usages is not helped to strengthen or
      enhance individual's level of internal or external political efficacy.
      Furthermore, hierarchical regression analyses demonstrate that information needs
      and recognition needs are positive predictors of internal political efficacy.
      Overall, these obtained findings may shed more up-to-date insights on the
      meaningful role of the mobile-based communication technology in promoting
      citizens' democratic engagement in a developing country.

PMID- 30092074
TI  - Aspergillus endocarditis: Diagnostic criteria and predictors of outcome, A
      retrospective cohort study.
AB  - BACKGROUND: Fungal Endocarditis (FE), a relatively rare disease, has a high rate
      of mortality and is associated with multiple morbidities. Aspergillus
      endocarditis (AE) is severe form of FE. Incidence of AE has increased and is
      expected to rise due to an increased frequency of invasive procedures, cardiac
      devices and prosthetic valves together with increased use of immune system
      suppressors. AE lacks most of the clinical criteria used to diagnose infective
      endocarditis (IE), where blood culture is almost always negative, and fever may
      be absent. Diagnosis is usually late and in many cases is made post-mortem. Late
      or mistaken diagnosis of AE contribute to delayed and incorrect management of
      patients. In the current study we aimed to describe the clinical, laboratory and
      imaging characteristics of AE, to identify predictors of early diagnosis of this
      serious infection. METHODS: Patients with definite/possible IE, as diagnosed by
      the Kasr Al-Ainy IE Working Group from February 2005 through June 2016, were
      reviewed in this study. We compared the demographic, clinical, laboratory and
      imaging criteria of AE patients to non-fungal IE patients. RESULTS: This study
      included 374 patients with IE in which FE accounted for 43 cases. Aspergillus was
      the most common fungus (31 patients; 8.3%) in the patient group. Lack of fever
      and acute limb ischemia at presentation were significantly associated with AE (p
      < 0.001, p = 0.014, respectively). Health care associated endocarditis (HAE) and
      prosthetic valve endocarditis (PVE) were the only significant risk factors
      associated with AE (p < 0.001 for each). Mitral, non-valvular, and aortotomy site
      vegetations, as well as aortic abscess/pseudoaneurysm, were significantly
      associated with AE (p = 0.022, p = 0.004, p < 0.001, and p < 0.001,
      respectively). Through multivariate regression analysis, HAE, PVE, aortic
      abscess/pseudoaneurysm, and lack of fever were strongly linked to AE. The
      probability of an IE patient having AE with HAE, PVE, and aortic
      abscess/pseudoaneurysm, but no fever, was 0.92. In contrast, the probability of
      an IE patient having AE with fever, native valve IE, but no health-care
      associated IE and no abscess/pseudoaneurysm, was 0.003. Severe sepsis and
      mortality in the Aspergillus group were higher as compared to the non-fungal
      group (p = 0.098 and 0.097, respectively). Thirteen AE patients died during
      hospitalization. PVE, the use of single versus dual antifungal agents, severe
      heart failure, and severe sepsis were significant predictors of mortality (p =
      0.008, 0.012, 0.003, and 0.01, respectively). CONCLUSION: To our knowledge, this
      is the first study to address diagnostic criteria for AE. Through multivariate
      regression analysis, absence of fever, HAE, PVE, and aortic
      abscess/pseudoaneurysm were strong predictors of AE. Use of these criteria my
      lead to earlier diagnoses of AE. Early treatment of AE patients with voriconazole
      in combination with other antifungal agents may be possible based on the
      previously mentioned criteria, which may facilitate better patient outcomes.

PMID- 30092077
TI  - Inferring space from time: On the relationship between demography and
      environmental suitability in the desert plant O. rastrera.
AB  - Demographic analyses and ecological niche modeling (ENM) are two popular tools
      that address species persistence in relation to environmental conditions. Classic
      demography provides detailed information about the mechanisms that allow a
      population to grow or remain stable at a local scale, while ENM infers
      distributions from conditions suitable for species persistence at geographic
      scales by relating species' occurrences with environmental variables. By
      integrating these two tools, we may better understand population processes that
      determine species persistence at a geographic scale. To test this idea, we
      developed a model that relates climate to demography of the cactus Opuntia
      rastrera using 15 years of data from one locality. Using this model we determined
      the geographic area where populations would have positive growth rates given its
      climatic conditions. The climate-dependent demographic model showed poor
      performance as a distribution model, but it was helpful in defining some
      mechanisms that determine species' distributions. For instance, high rainfall had
      a negative impact on the population growth rate by increasing mortality. Rainy
      areas to the west of the distribution of O. rastrera were identified as
      unsuitable both by our climate-dependent demographic model and by a popular ENM
      algorithm (MaxEnt), suggesting that distribution is constrained by excessive
      rains due to high mortality. Areas projected to be climatically suitable by
      MaxEnt were not related with higher population growth rates. Instead, we found a
      strong correlation between environmental distance to the niche centroid (center
      of the niche hypervolume, where optimal conditions may occur) and population
      growth rate, meaning that the niche centroid approach is helpful in finding high
      fitness areas.

PMID- 30092078
TI  - Prognostic significance of preoperative CT findings in patients with advanced
      gastric cancer who underwent curative gastrectomy.
AB  - BACKGROUND: Preoperative therapy has gained wide interest in advanced gastric
      cancer patients due to its potential advantages of improved disease control.
      Selection of high risk patients based on preoperative staging is crucial to
      choose the candidates for neoadjuvant therapy. METHODS: Our institutional review
      board approved this retrospective study and waived the requirement for patient
      consent. We searched 394 advanced gastric cancer patients (pT2-4) who underwent
      curative resection in 2010 without neoadjuvant therapies. Two abdominal
      radiologists independently reviewed the preoperative CT including tumor depth on
      CT (CT-tumor depth), which was categorized as follows: intramural, minimal
      extramural(<1mm), spiculated extramural(>=1mm) and nodular extramural
      infiltration. The impact of clinicoradiologic factors on disease recurrence and
      disease free survival (DFS) was evaluated. Recursive partitioning analysis was
      performed to suggest prediction models for recurrence. RESULTS: Of total 394
      patients, 86 patients (21.8%) experienced recurrence. Spiculated (>=1mm) and
      nodular extramural tumor infiltration and CT size of 5-10cm were independent
      predictors of disease recurrence and significantly associated with worse DFS.
      Lymph node involvement on CT was not significantly associated with patient
      outcome. Among patients with same pT4a stage, the recurrence rate rises and DFS
      gets worse as the extramural tumor infiltration progresses (P < 0.001). The
      prediction model for recurrence revealed that size and CT-tumor depth were the
      two major discriminating factors. CONCLUSION: CT-tumor depth and size could be
      used as independent predictors for prognosis. Preoperative CT can be used for
      prognostic stratification to select high risk patients for whom neoadjuvant
      therapies might be considered.

PMID- 30092079
TI  - Vanadium stimulates pepper plant growth and flowering, increases concentrations
      of amino acids, sugars and chlorophylls, and modifies nutrient concentrations.
AB  - Vanadium (V) can be absorbed by plants and regulate their growth and development,
      although contrasting effects have been reported among species and handling
      conditions. The objective of this work was to evaluate the beneficial effect of V
      on pepper plants (Capsicum annuum L.). The plants were grown in a hydroponic
      system with the application of four V concentrations (0, 5, 10, and 15 MUM
      NH4VO3). Four weeks after the beginning of the treatments, growth, flowering,
      biomass, chlorophyll concentration, total amino acids, total soluble sugars, and
      nutrients were determined in leaves, stems, and roots. The application of 5 MUM V
      increased plant growth, induced floral bud development, and accelerated
      flowering. The chlorophyll concentration varied according to the type of plant
      part analyzed. The concentrations of amino acids and sugars in leaves and roots
      were higher with 5 MUM. With 10 and 15 MUM V, the plants were smaller and showed
      toxicity symptoms. The K concentration in leaves decreased as the V dose
      increased (0 to 15 MUM). However, 5 MUM V increased the concentrations of N, P,
      K, Ca, Mg, Cu, Mn, and B, exclusively in stems. The application of 15 MUM V
      decreased the concentrations of Mg and Mn in leaves, but increased those of P,
      Ca, Mg, Cu, and B in roots. We conclude that V has positive effects on pepper
      growth and development, as well as on the concentrations of amino acids and total
      sugars. V was antagonistic with K, Mg, and Mn in leaves, while in stems and
      roots, there was synergism with macro and micronutrients. Vanadium is a
      beneficial element with the potential to be used in biostimulation approaches of
      crops like pepper.

PMID- 30092080
TI  - Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity.
AB  - In the context of type 1 diabetes research and the development of insulin
      producing beta-cell replacement strategies, whether pancreatic ductal cells
      retain their developmental capability to adopt an endocrine cell identity remains
      debated, most likely due to the diversity of models employed to induce pancreatic
      regeneration. In this work, rather than injuring the pancreas, we developed a
      mouse model allowing the inducible misexpression of the proendocrine gene Neurog3
      in ductal cells in vivo. These animals developed a progressive islet hypertrophy
      attributed to a proportional increase in all endocrine cell populations. Lineage
      tracing experiments indicated a continuous neo-generation of endocrine cells
      exhibiting a ductal ontogeny. Interestingly, the resulting supplementary beta
      like cells were found to be functional. Based on these findings, we suggest that
      ductal cells could represent a renewable source of new beta-like cells and that
      strategies aiming at controlling the expression of Neurog3, or of its molecular
      targets/co-factors, may pave new avenues for the improved treatments of diabetes.

PMID- 30092081
TI  - Complications of bone-anchored prostheses for individuals with an extremity
      amputation: A systematic review.
AB  - BACKGROUND: This study aimed to provide an overview of device-related
      complications occurring in individuals with an upper or lower extremity
      amputation treated with a screw, press-fit or other type of bone-anchored implant
      as well as interventions related to these complications. METHOD: A systematic
      literature search was conducted in the MEDLINE, Cochrane, EMBASE, CINAHL and Web
      of Science databases. The included studies reported on device-related
      complications and interventions occurring in individuals with bone-anchored
      prostheses. The outcomes evaluated were death, infection, bone/device breakage,
      implant loosening, soft tissue complications, systemic events, antibiotic and
      surgical treatment. Subgroup analyses were performed for the following groups: a)
      implant type (screw, press-fit and other types of implants) and b) level of
      amputation (transfemoral, transtibial and upper extremity amputation). RESULTS:
      Of 309 studies, 12 cohort studies were eligible for inclusion, all of which had
      methodological shortcomings and 12 studies were excluded due to complete overlap
      of patient data. Implant infection were rare in certain transfemoral implants
      (screw: 2-11%, press-fit: 0-3%, Compress: 0%) but common in transtibial implants
      (29%). The same was observed for implant loosening, in transfemoral (screw: 6%,
      press-fit: 0-3%, Compress: 0%), transtibial implants (29%) as well as for upper
      extremity implants (13-23%). Intramedullary device breakage were rare in
      transfemoral implants (screw: 0%, press-fit: 1%, Compress: unknown) but frequent
      in individuals with transradial implants (27%) and absent in transtibial
      implants. Soft tissue infections and complications were common and underreported
      in most articles. CONCLUSIONS: Major complications (e.g. implant infection,
      implant loosening and intramedullary device breakage) are rare in transfemoral
      bone-anchored prosthesis and seem to occur less frequently in individuals with
      press-fit implants. Minor complications, such as soft tissue infections and
      complications, are common but are substantially influenced by the learning curve,
      implant design and surgical technique. Data for patients treated with a
      transtibial, upper extremity or Compress implant are underreported, precluding
      definitive conclusions. There is a need for either an international database to
      report on or a standard core set of complications as well as the need to follow
      classification systems that result in unequivocal data.

PMID- 30092082
TI  - Lung injury does not aggravate mechanical ventilation-induced early cerebral
      inflammation or apoptosis in an animal model.
AB  - INTRODUCTION: The acute respiratory distress syndrome is not only associated with
      a high mortality, but also goes along with cognitive impairment in survivors. The
      cause for this cognitive impairment is still not clear. One possible mechanism
      could be cerebral inflammation as result of a "lung-brain-crosstalk". Even
      mechanical ventilation itself can induce cerebral inflammation. We hypothesized,
      that an acute lung injury aggravates the cerebral inflammation induced by
      mechanical ventilation itself and leads to neuronal damage. METHODS: After
      approval of the institutional and state animal care committee 20 pigs were
      randomized to one of three groups: lung injury by central venous injection of
      oleic acid (n = 8), lung injury by bronchoalveolar lavage in combination with one
      hour of injurious ventilation (n = 8) or control (n = 6). Brain tissue of four
      native animals from a different study served as native group. For six hours all
      animals were ventilated with a tidal volume of 7 ml kg-1 and a scheme for
      positive end-expiratory pressure and inspired oxygen fraction, which was adapted
      from the ARDS network tables. Afterwards the animals were killed and the brains
      were harvested for histological (number of neurons and microglia) and molecular
      biologic (TNFalpha, IL-1beta, and IL-6) examinations. RESULTS: There was no
      difference in the number of neurons or microglia cells between the groups.
      TNFalpha was significantly higher in all groups compared to native (p < 0.05), IL
      6 was only increased in the lavage group compared to native (p < 0.05), IL-1beta
      showed no difference between the groups. DISCUSSION: With our data we can confirm
      earlier results, that mechanical ventilation itself seems to trigger cerebral
      inflammation. This is not aggravated by acute lung injury, at least not within
      the first 6 hours after onset. Nevertheless, it seems too early to dismiss the
      idea of lung-injury induced cerebral inflammation, as 6 hours might be just not
      enough time to see any profound effect.

PMID- 30092083
TI  - Pseudomonas aeruginosa nfuA: Gene regulation and its physiological roles in
      sustaining growth under stress and anaerobic conditions and maintaining bacterial
      virulence.
AB  - The role of the nfuA gene encoding an iron-sulfur ([Fe-S]) cluster-delivery
      protein in the pathogenic bacterium Pseudomonas aeruginosa was investigated. The
      analysis of nfuA expression under various stress conditions showed that
      superoxide generators, a thiol-depleting agent and CuCl2 highly induced nfuA
      expression. The expression of nfuA was regulated by a global [2Fe-2S] cluster
      containing the transcription regulator IscR. Increased expression of nfuA in the
      DeltaiscR mutant under uninduced conditions suggests that IscR acts as a
      transcriptional repressor. In vitro experiments revealed that IscR directly bound
      to a sequence homologous to the Escherichia coli Type-I IscR-binding motifs on a
      putative nfuA promoter that overlapped the -35 element. Binding of IscR prevented
      RNA polymerase from binding to the nfuA promoter, leading to repression of the
      nfuA transcription. Physiologically, deletion of nfuA reduced the bacterial
      ability to cope with oxidative stress, iron deprivation conditions and attenuated
      virulence in the Caenorhabditis elegans infection model. Site-directed
      mutagenesis analysis revealed that the conserved CXXC motif of the Nfu-type
      scaffold protein domain at the N-terminus was required for the NfuA functions in
      conferring the stress resistance phenotype. Furthermore, anaerobic growth of the
      DeltanfuA mutant in the presence of nitrate was drastically retarded. This
      phenotype was associated with a reduction in the [Fe-S] cluster containing
      nitrate reductase enzyme activity. However, NfuA was not required for the
      maturation of [Fe-S]-containing proteins such as aconitase, succinate
      dehydrogenase, SoxR and IscR. Taken together, our results indicate that NfuA
      functions in [Fe-S] cluster delivery to selected target proteins that link to
      many physiological processes such as anaerobic growth, bacterial virulence and
      stress responses in P. aeruginosa.

PMID- 30092084
TI  - Complement receptor 1 (CR1, CD35) association with susceptibility to leprosy.
AB  - BACKGROUND: Pathophysiological mechanisms are still incompletely understood for
      leprosy, an urgent public health issue in Brazil. Complement receptor 1 (CR1)
      binds complement fragments C3b/C4b deposited on mycobacteria, mediating its
      entrance in macrophages. We investigated CR1 polymorphisms, gene expression and
      soluble CR1 levels in a case-control study with Brazilian leprosy patients,
      aiming to understand the role of this receptor in differential susceptibility to
      the disease. METHODOLOGY: Nine polymorphisms were haplotyped by multiplex PCR-SSP
      in 213 leprosy patients (47% multibacillary) and 297 controls. mRNA levels were
      measured by qPCR and sCR1 by ELISA, in up to 80 samples. PRINCIPAL FINDINGS:
      Individuals with the most common recombinant haplotype harboring rs3849266*T in
      intron 21 and rs3737002*T in exon 26 (encoding p.1408Met of the York Yka+
      antigen), presented twice higher susceptibility to leprosy (OR = 2.43, p =
      0.017). Paucibacillary patients with these variants presented lower sCR1 levels,
      thus reducing the anti-inflammatory response (p = 0.040 and p = 0.046,
      respectively). Furthermore, the most ancient haplotype increased susceptibility
      to the multibacillary clinical form (OR = 3.04, p = 0.01) and presented the
      intronic rs12034383*G allele, which was associated with higher gene expression (p
      = 0.043), probably increasing internalization of the parasite. Furthermore, there
      was an inverse correlation between the levels of sCR1 and mannose-binding lectin
      (initiator molecule of the lectin pathway of complement, recognized by CR1) (R = 
      0.52, p = 0.007). CONCLUSIONS: The results lead us to suggest a regulatory role
      for CR1 polymorphisms on mRNA and sCR1 levels, with haplotype-specific effects
      increasing susceptibility to leprosy, probably by enhancing parasite phagocytosis
      and inflammation.

PMID- 30092085
TI  - Validity and time course of surgical fear as measured with the Surgical Fear
      Questionnaire in patients undergoing cataract surgery.
AB  - OBJECTIVES: The primary aim of the study was to assess the convergent validity of
      the Surgical Fear Questionnaire (SFQ) with other self-report instruments and
      biological indices of stress. Secondary aims were the examination of predictors
      of the level and time course of fear and preferences for fear treatment. METHODS:
      In a prospective observational cohort study SFQ short-term (SFQ-s) and long-term
      (SFQ-l) scores were assessed one week, one day, and the morning before cataract
      surgery, together with salivary cortisol and alpha-amylase (sAA) levels, and
      numeric rating scale (NRS) fear score. SFQ-scores were also assessed before
      second eye surgery. Expected pain and recovery, and sociodemographic and medico
      psychological predictors of fear were assessed at baseline. RESULTS: Data of 98
      patients were analyzed. Scores of both SFQ-subscales (range 0-40) were generally
      low, all mean <= 9.0. SFQ-s and SFQ-l correlated significantly with the other
      self-report instruments: NRS fear .83 and .89, expected pain .49 and .54,
      expected recovery -.27 and -.44. No association was found between SFQ-scores and
      cortisol or sAA level. Predictors of the level of fear were baseline pain and
      stress. Additional effects of time were found for subgroups based on educational
      level, antidepressant use, and presurgical stress (SFQ-l). SFQ-scores were
      significantly lower before the second cataract surgery than before the first, and
      higher in patients who would have appreciated treatment of fear. DISCUSSION:
      Convergent validity of the SFQ with other self-report measures is shown. The
      sensitivity of the SFQ permits the detection of small variations in fear caused
      by time or other factors.

PMID- 30092087
TI  - Trends and factors associated with pregnancies among adolescent women in Nepal:
      Pooled analysis of Nepal Demographic and Health Surveys (2006, 2011 and 2016).
AB  - INTRODUCTION: Adolescent pregnancy is a significant cost to mother, newborn, and
      their family and society. Despite the enormous health and social impact of
      adolescent pregnancy, there is a dearth of nationally representative studies on
      factors associated with adolescent pregnancies in Nepal. Therefore, this study
      aimed to examine trends and factors associated with adolescent pregnancies in
      Nepal, using pooled data of three nationally representative demographic surveys.
      METHODS: Data for this study was derived from the recent three consecutive (2006,
      2011 and 2016) Nepal Demographic and Health Surveys (NDHS). A total of 7,788
      adolescent women aged 15-19 years included in the analysis. Trends and
      multivariable logistic regression analysis was performed to examine the factors
      associated with adolescent pregnancy. RESULTS: Over the study period (2006-2016),
      the rate of adolescent pregnancy was 173 [95% Confidence Interval (CI): 159, 188]
      per 1000 women aged 15-19 years. Adolescent pregnancy was significantly higher
      among woman with middle household wealth index [adjusted Odds Ratio (aOR) 2.19,
      95% confidence interval CI 1.65, 2.91] or poor household wealth index (aOR 2.37,
      95% CI 1.76, 3.21). Similarly, Dalit (aOR 1.87, 95% CI 1.50, 2.34) or Madhesi
      (aOR 1.67, 95% CI 1.32, 2.11); and unemployed (aOR 1.28, 95% CI 1.09, 1.50) women
      had higher odds of adolescent pregnancies. In contrast, adolescent pregnancy was
      significantly lower among educated women (aOR 0.60, 95% CI 0.48, 0.74), and women
      with access to media exposure to public health issues (aOR 0.75, 95% CI 0.64,
      0.88). CONCLUSIONS: Access to the media exposure on public health issues can be
      the effective efforts to reduce adolescent pregnancy. Women who have low maternal
      education, low wealth index, unemployed, and ethnic groups such as Dalits, and
      Madeshi needs to be targeted while designing and implementing policies and
      programs.

PMID- 30092088
TI  - Nitrogen deposition does not alleviate the adverse effects of shade on Camellia
      japonica (Naidong) seedlings.
AB  - Camellia japonica (Naidong), a Tertiary relict species with a unique biological
      and cultural characteristic, is a special ecotype of C. japonica and is the
      northernmost distributed populations of C. japonica in the world. This study
      investigated the interactive responses of C. japonica (Naidong) to shade and
      nitrogen deposition focusing on seedling growth, leaf morphology and leaf
      physiology under two light regimes (15% and 65% of full sunlight to represent
      deep shade and slight shade respectively) and three nitrogen deposition regimes
      (0, 6 and 12 g N m-2 year-1) in a greenhouse. After 123 d of treatment, the
      results showed that the deep shade reduced the growth of seedlings significantly
      compared to slight shade, but improved the specific leaf area, leaf water
      content, chlorophyll content and Fv/Fm of plants. Moderate nitrogen (6 g N m-2
      year-1) supply increased the crown area, specific leaf area, leaf water content,
      chlorophyll content and water use efficiency of seedlings. However, high nitrogen
      (12 g N m-2 year-1) supply reduced the basal diameter, crown area, specific leaf
      area and leaf water content. No significant interaction of shade and nitrogen
      deposition on C. japonica (Naidong) was found. There is a threshold of nitrogen
      deposition for the growth of C. japonica (Naidong). Camellia japonica (Naidong)
      populations should be protected by collecting of germplasm resources and carrying
      out the ex situ conservation.

PMID- 30092086
TI  - Clathrin-dependent endocytosis is associated with RNAi response in the western
      corn rootworm, Diabrotica virgifera virgifera LeConte.
AB  - The cellular uptake of dsRNA after dietary exposure is critical for RNAi
      efficiency; however, the mechanism of its uptake in many insects remains to be
      understood. In this study, we evaluated the roles of the endocytic pathway genes
      Clathrin heavy chain (Chc), Clathrin adaptor protein AP50, ADP ribosylation
      factor-like 1 (Arf72A), Vacuolar H+ ATPase 16 kDa subunit (Vha16), and small
      GTPase Rab7 and putative sid-1-like genes (silA and silC) in RNAi response in
      western corn rootworm (WCR) using a two-stage dsRNA exposure bioassay. Silencing
      of Chc, Vha16, and AP50 led to a significant decrease in the effects of laccase2
      dsRNA reporter, indicating that these genes are involved in RNAi response.
      However, the knockdown of either Arf72A or Rab7 did not suppress the response to
      laccase2 dsRNA. The silencing of the silC gene did not lead to a significant
      reduction in mortality or increase in the expression of V-ATPase A reporter.
      While the silencing of the silA gene significantly decreased insect mortality,
      significant changes in V-ATPase A expression were not detected. These results
      suggest that clathrin-dependent endocytosis is a biological mechanism that plays
      an important role during RNAi response in WCR adults. The fact that no definitive
      support for the roles of silA or silC in RNAi response was obtained support the
      idea that RNAi response varies greatly in different insect species, demanding
      additional studies focused on elucidating their involvement in this mechanism.

PMID- 30092089
TI  - The occurrence of Treponema spp. in gingival plaque from dogs with varying degree
      of periodontal disease.
AB  - Periodontal disease is common in dogs and is initiated by gingival plaque
      composed of several hundred bacterial species. Some of these species have
      specifically been pointed out as potential periodontal pathogens, such as
      Treponema spp. Treponema spp. are difficult to culture and therefore the majority
      have been detected by culture-independent methods, such as PCR (Polymerase Chain
      Reaction). This leaves many Treponema spp. uncharacterized and unnamed. In this
      study, treponemes were investigated in gingival plaque from dogs with varying
      degree of periodontal disease with the aim to describe their occurrence and
      diversity in dogs. The methods used were culture, phase-contrast microscopy, PCR
      targeting the 16SrRNA-tRNAIle intergenic spacer region (ISR2), sequencing of the
      ISR2 and phylogenetic analysis. Treponema spp. were detected in samples from 10
      out of 11 dogs and isolates were obtained from six dogs. Both healthy and
      periodontitis affected dogs were Treponema positive. Phylogenetic analysis, based
      on ISR2 sequences, revealed a large diversity of treponemes in the study
      population that were found to be distributed mainly in two groups, corresponding
      to the human oral treponeme phylogroups II (Treponema denticola) and IV
      (Treponema maltophilum) genetic groups. They were generally more distantly
      related to other treponemes in these groups. Treponemes from dogs with
      periodontitis and dogs with mild gingivitis without periodontitis did not differ
      in any obvious way. The results indicate that several phylotypes of oral
      treponemes are common in dogs regardless of periodontal status.

PMID- 30092090
TI  - The impact of the patient's initial NACA score on subjective and physiological
      indicators of workload during pre-hospital emergency care.
AB  - BACKGROUND: Excessive workload may impair patient safety. However, little is
      known about emergency care providers' workload during the treatment of life
      threatening cases including cardiopulmonary resuscitation (CPR). Therefore, we
      tested the hypothesis that subjective and physiological indicators of workload
      are associated with the patient's initial NACA score and that workload is
      particularly high during CPR. METHODS: NASA task load index (NASA-tlx) and alarm
      codes were obtained for 216 sorties of pre-hospital emergency medical care.
      Furthermore, initial NACA scores of 140 patients were extracted from the
      physicians' protocols. The physiological workload indicators mean heart rate (HR)
      and permutation entropy (PeEn) were calculated for 51 sorties of primary care.
      General linear mixed models were used to analyze the association of NACA scores
      with subjective (NASA-tlx) and physiological (mean HR, PeEn) measures of
      workload. RESULTS: In contrast to the physiological variables PeEn (p = 0.10) and
      HR (p = 0.19), the mental (p<0.001) and temporal demands (p<0.001) as well as the
      effort (p<0.001) and frustration (p = 0.04) subscale of the NASA-tlx were
      significantly associated with initial NACA scores. Compared to NACA = I, an
      initial NACA score of VI (representing CPR) increased workload by a mean of
      389.5% (p = 0.001) in the mental and 345.9% (p<0.001) in the temporal demands,
      effort by a mean of 446,8% (p = 0.002) and frustration by 190.0% (p = 0.03). In
      line with the increase in NASA-tlx, PeEn increased by 20.6% (p = 0.01) and HR by
      6.4% (p = 0.57). CONCLUSIONS: Patients' initial NACA scores are associated with
      subjective workload. Workload was highest during CPR.

PMID- 30092091
TI  - Phylogenetic analysis of the mitochondrial genomes in bees (Hymenoptera: Apoidea:
      Anthophila).
AB  - In this study, the first complete mitogenome of Andrenidae, namely Andrena
      camellia, is newly sequenced. It includes 13 protein-coding (PCG) genes, 22
      transfer RNA (rRNA) genes, two ribosomal RNA (tRNA) genes, and a control region.
      Among PCGs, high conservation is observed in cytochrome oxidase genes with cox1
      exhibits the highest conservation. Conversely, NADH dehydrogenase and ATPase
      subunit genes are more variable with atp8 presents the maximal variation.
      Comparison of the gene order indicates complex rearrangement in bees. Most of the
      rearranged events are located in the tRNA clusters of trnI-trnQ-trnM, trnW-trnC
      trnY, and trnA-trnR-trnN-trnS1-trnE-trnF. Furthermore, we present the most
      comprehensive mitochondrial phylogeny of bee families. The monophyly of each
      family and the long-tongued bees is highly supported. However, short-tongued bees
      are inferred as paraphyletic relative to the sister relationship between
      Melittidae and other bee families. Furthermore, to improve the resolution of
      phylogeny, various datasets and analytical approaches are performed. It is
      indicated that datasets including third codons of PCGs facilitate to produce
      identical topology and higher nodal support. The tRNA genes that have typical
      cloverleaf secondary structures also exhibit similar positive effects. However,
      rRNAs present poor sequence alignment and distinct substitution saturation, which
      result in negative effects on both tree topology and nodal support. In addition,
      Gblocks treatment can increase the congruence of topologies, but has opposite
      effects on nodal support between the two inference methods of maximum likelihood
      and Bayesian inference.

PMID- 30092092
TI  - Multimodal cortical and subcortical exercise compared with treadmill training for
      spinal cord injury.
AB  - BACKGROUND AND PURPOSE: Spared fibers after spinal cord injury (SCI) tend to
      consist predominantly of subcortical circuits that are not under volitional
      (cortical) control. We aim to improve function after SCI by using targeted
      physical exercises designed to simultaneously stimulate cortical and spared
      subcortical neural circuits. METHODS: Participants with chronic motor-incomplete
      SCI enrolled in a single-center, prospective interventional crossover study.
      Participants underwent 48 sessions each of weight-supported robotic-assisted
      treadmill training and a novel combination of balance and fine hand exercises, in
      randomized order, with a 6-week washout period. Change post-intervention was
      measured for lower extremity motor score, soleus H-reflex facilitation; seated
      balance function; ambulation; spasticity; and pain. RESULTS: Only 9 of 21
      enrolled participants completed both interventions. Thirteen participants
      completed at least one intervention. Although there were no statistically
      significant differences, multimodal training tended to increase short-interval H
      reflex facilitation, whereas treadmill training tended to improve dynamic seated
      balance. DISCUSSION: The low number of participants who completed both phases of
      the crossover intervention limited the power of this study to detect significant
      effects. Other potential explanations for the lack of significant differences
      with multimodal training could include insufficient engagement of lower extremity
      motor cortex using skilled upper extremity exercises; and lack of skill transfer
      from upright postural stability during multimodal training to seated dynamic
      balance during testing. To our knowledge, this is the first published study to
      report seated posturography outcomes after rehabilitation interventions in
      individuals with SCI. CONCLUSION: In participants with chronic incomplete SCI, a
      novel mix of multimodal exercises incorporating balance exercises with skilled
      upper extremity exercises showed no benefit compared to an active control program
      of body weight-supported treadmill training. To improve participant retention in
      long-term rehabilitation studies, subsequent trials would benefit from a parallel
      group rather than crossover study design.

PMID- 30092093
TI  - Bat pathogens hit the road: But which one?

PMID- 30092094
TI  - Bird-building collision risk: An assessment of the collision risk of birds with
      buildings by phylogeny and behavior using two citizen-science datasets.
AB  - Bird collisions with buildings are the second largest anthropogenic source of
      direct mortality for birds (365-988 million birds killed annually in the United
      States). Recent research suggests that this mortality occurs disproportionately
      across species. However, previous work had relied on regional and annual measures
      of relative species abundance. Our research identifies which species experience
      higher or lower collision rates than expected from local abundances using two
      sets of citizen science data: Minnesota Project BirdSafe and the Mississippi
      River Twin Cities Important Bird Area Landbird Monitoring Program. Our analysis
      used a measure of relative species abundance that spatially overlaps the area
      monitored for building collisions and was measured weekly, allowing for a
      temporally and spatially more specific analysis than most previous analyses.
      Abundance and collision data were used to model phylogenetic and behavioral
      traits associated with increased collision risk. Behavioral traits included
      diurnal/nocturnal migration timing, length of migration, and foraging strategies.
      Our analysis shows that birds that predominately migrate during the day have a
      decreased risk of building collisions despite peak collision numbers occurring
      during early morning; this result suggests that more nuanced behavioral or
      physiological differences between diurnal and nocturnal migrants could contribute
      to bird-building collision risk. Additionally, for many species, local abundance
      is the predominant determining factor for collision risk. However, for ~20% of
      species studied, the family, genus, and/or species of a bird may affect the
      collision risk.

PMID- 30092095
TI  - Mobile apps for treatment of speech disorders in children: An evidence-based
      analysis of quality and efficacy.
AB  - BACKGROUND: Recently there has been exponential growth in mobile health (mHealth)
      applications (apps) for children with speech disorders. A challenge for health
      professionals and families is knowing how to find high quality apps that are
      therapeutically beneficial. We systematically search and critique the quality of
      mobile apps for childhood speech disorders. An evidence-based method for
      identifying suitable apps in the Google Play and Apple iTunes stores is also
      proposed. METHODS AND FINDINGS: A systematic search of the Google Play and Apple
      iTunes app stores was conducted from November 2016 to May 2017. Twelve pre
      defined search terms were applied, identifying 5076 apps. Systematic screening
      resulted in 132 unique apps for full appraisal. These were appraised by two
      raters using the Mobile Application Rating scale. None were of excellent quality.
      Twenty-five were of good quality, 105 average and 2 were poor or very poor.
      DISCUSSION: It can be challenging for consumers to locate high quality speech
      therapy apps for children. Although we found more than 5000 apps, less than 3%
      met criteria for evaluation. Difficulties sourcing valid apps included: (i)
      Boolean operators were not available and therefore only one search term could be
      used each time (ii) the order of app listings in online stores continually
      changed (iii) apps were organised in online stores according to relevance and
      popularity (iv) there was no easy way to extract app titles and eliminate
      duplicates (v) app cost did not always correlate with therapeutic quality.
      CONCLUSIONS: The rapid growth of mHealth heightens the need to develop rigorous
      and efficient systems to search and retrieve apps and evaluate their therapeutic
      benefits. Given the difficulty accessing speech therapy services worldwide,
      mHealth promises therapy benefits when apps are reliable, valid and easily found.

PMID- 30092098
TI  - Correction: Tissue and serum expression of TGM-3 may be prognostic marker in
      patients of oral squamous cell carcinoma undergoing chemo-radiotherapy.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199665.].

PMID- 30092096
TI  - High glucose-induced oxidative stress impairs proliferation and migration of
      human gingival fibroblasts.
AB  - Delayed gingival wound healing is widely observed in periodontal patients with
      diabetes. However, the molecular mechanisms of the impaired function of gingival
      fibroblasts in diabetes remain unclear. The purpose of this study was to
      investigate changes in the properties of human gingival fibroblasts (HGFs) under
      high-glucose conditions. Primary HGFs were isolated from healthy gingiva and
      cultured with 5.5, 25, 50, and 75 mM glucose for 72 h. In vitro wound healing, 5
      ethynyl-2'-deoxyuridine (EdU), and water-soluble tetrazolium salt (WST-8) assays
      were performed to examine cell migration and proliferation. Lactase dehydrogenase
      (LDH) levels were measured to determine cytotoxicity. The mRNA expression levels
      of oxidative stress markers were quantified by real-time PCR. Intracellular
      reactive oxygen species (ROS) were also measured in live cells. The antioxidant N
      acetyl-l-cysteine (NAC, 1 mM) was added to evaluate the involvement of ROS in the
      glucose effect on HGFs. As a result, the in vitro wound healing assay showed that
      high glucose levels significantly reduced fibroblast migration and proliferation
      at 6, 12, 24, 36, and 48 h. The numbers of cells positive for EdU staining were
      decreased, as was cell viability, at 50 and 75 mM glucose. A significant increase
      in LDH was proportional to the glucose concentration. The mRNA levels of heme
      oxygenase-1 and superoxide dismutase-1 and ROS levels were significantly
      increased in HGFs after 72 h of exposure to 50 mM glucose concentration. The
      addition of NAC diminished the inhibitory effect of high glucose in the in vitro
      wound healing assay. The results of the present study show that high glucose
      impairs the proliferation and migration of HGFs. Fibroblast dysfunction may
      therefore be caused by high glucose-induced oxidative stress and may explain the
      delayed gingival wound healing in diabetic patients.

PMID- 30092097
TI  - Exploring potential roles for the interaction of MOM1 with SUMO and the SUMO E3
      ligase-like protein PIAL2 in transcriptional silencing.
AB  - The CHD3-like chromatin remodeling protein MOM1 and the PIAS-type SUMO E3 ligase
      like protein PIAL2 are known to interact with each other and mediate
      transcriptional silencing in Arabidopsis. However, it is poorly understood
      whether and how the interaction is involved in transcriptional silencing. Here,
      we demonstrate that, while the PIAL2 interaction domain (PIAL2-IND) is required
      for PIAL2 dimerization, MOM-PIAL2 interaction, and transcriptional silencing, a
      transgene fusing the wild-type MOM1 protein with the PIAL2 protein defective in
      PIAL2-IND can completely restore transcriptional silencing in the mom1/pial2
      double mutant, demonstrating that the artificial fusion of MOM1 and PIAL2 mimics
      the in vivo interaction of these two proteins so that PIAL2-IND is no longer
      required for transcriptional silencing in the fusion protein. Further, our yeast
      two-hybrid assay identifies a previously unrecognized SUMO interaction motif
      (SIM) in the conserved MOM1 motif CMM3 and demonstrates that the SIM is
      responsible for the interaction of MOM1 with SUMO. Given that eukaryotic PIAS
      type SUMO E3 ligases have a conserved role in chromatin regulation, the findings
      reported in this study may represent a conserved chromatin regulatory mechanism
      in higher eukaryotes.

PMID- 30092099
TI  - Estimated global overweight and obesity burden in pregnant women based on panel
      data model.
AB  - OBJECTIVE: To estimate the global and country-level burden of overweight and
      obesity among pregnant women from 2005 to 2014. METHODS: Publicly accessible
      country-level data were collected from the World Health Organization, the World
      Bank and the Food and Agricultural Organization. We estimated the number of
      overweight and obese pregnant women among 184 countries and determined the time
      related trend from 2005 to 2014. Based on panel data model, we determined the
      effects of food energy supply, urbanization, gross national income and female
      employment on the number of overweight and obese pregnant women. RESULTS: We
      estimated that 38.9 million overweight and obese pregnant women and 14.6 million
      obese pregnant women existed globally in 2014. In upper middle income countries
      and lower middle income countries, there were sharp increases in the number of
      overweight and obese pregnant women. In 2014, the percentage of female with
      overweight and obesity in India was 21.7%, and India had the largest number of
      overweight and obese pregnant women (4.3 million), which accounted for 11.1% in
      the world. In the United States of America, a third of women were obese, and the
      number of obese pregnant women was 1.1 million. In high income countries, caloric
      supply and urbanization were positively associated with the number of overweight
      and obese pregnant women. The percentage of employment in agriculture was
      inversely associated with the number of overweight and obese pregnant women, but
      only in upper middle income countries and lower middle income countries.
      CONCLUSION: The number of overweight and obese pregnant women has increased in
      high income and middle income countries. Environmental changes could lead to
      increased caloric supply and decreased energy expenditure among women. National
      and local governments should work together to create a healthy food environment.

PMID- 30092102
TI  - From chemistry to fruit flies: An unpredictable series of fortunate
      conversations.

PMID- 30092101
TI  - Individual investment decision behaviors based on demographic characteristics:
      Case from China.
AB  - Predicting and analyzing behaviors of investors is of great value to financial
      institutions. This paper uses survey data from about 9,000 individual investors
      across China to explore the predictability of decision behaviors by studying
      demographic characteristics that are relatively easy to obtain. After applying
      Pearson's chi-squared test, Spearman rank correlation test, and several data
      mining methods, we verified that demographic characteristics are closely linked
      to decision behaviors, and it would be an economical and feasible solution for
      financial organizations to build initial behavioral prediction models especially
      when investors' behavioral data are insufficient.

PMID- 30092100
TI  - TAK-272 (imarikiren), a novel renin inhibitor, improves cardiac remodeling and
      mortality in a murine heart failure model.
AB  - The renin-angiotensin system (RAS), which plays an important role in the
      progression of heart failure, is efficiently blocked by the inhibition of renin,
      the rate-limiting enzyme in the RAS cascade. In the present study, we
      investigated the cardioprotective effects of TAK-272 (SCO-272, imarikiren), a
      novel, orally effective direct renin inhibitor (DRI), and compared its efficacy
      with that of aliskiren, a DRI that is already available in the market. TAK-272
      was administered to calsequestrin transgenic (CSQ-tg) heart failure mouse model
      that show severe symptoms and high mortality. The CSQ-tg mice treated with 300
      mg/kg, the highest dose tested, of TAK-272 showed significantly reduced plasma
      renin activity (PRA), cardiac hypertrophy, and lung congestion. Further, TAK-272
      reduced cardiomyocyte injury accompanied by an attenuation of the increase in
      NADPH oxidase 4 and nitric oxide synthase 3 expressions. TAK-272 also prolonged
      the survival of CSQ-tg mice in a dose-dependent manner (30 mg/kg: P = 0.42, 100
      mg/kg: P = 0.12, 300 mg/kg: P < 0.01). Additionally, when compared at the same
      dose level (300 mg/kg), TAK-272 showed strong and sustained PRA inhibition and
      reduced the heart weight and plasma N-terminal pro-brain natriuretic peptide (NT
      proBNP) concentration, a heart failure biomarker, while aliskiren showed a
      significant weaker PRA inhibition and failed to demonstrate any cardioprotective
      effects. Our results showed that TAK-272 is an orally active and persistent renin
      inhibitor, which reduced the mortality of CSQ-tg mice and conferred protection
      against cardiac hypertrophy and injury. Thus, TAK-272 treatment could provide a
      new therapeutic approach for heart failure.

PMID- 30092103
TI  - Extended darkness induces internal turnover of glucosinolates in Arabidopsis
      thaliana leaves.
AB  - Prolonged darkness leads to carbohydrate starvation, and as a consequence plants
      degrade proteins and lipids to oxidize amino acids and fatty acids as alternative
      substrates for mitochondrial ATP production. We investigated, whether the
      internal breakdown of glucosinolates, a major class of sulfur-containing
      secondary metabolites, might be an additional component of the carbohydrate
      starvation response in Arabidopsis thaliana (A. thaliana). The glucosinolate
      content of A. thaliana leaves was strongly reduced after seven days of darkness.
      We also detected a significant increase in the activity of myrosinase, the enzyme
      catalyzing the initial step in glucosinolate breakdown, coinciding with a strong
      induction of the main leaf myrosinase isoforms TGG1 and TGG2. In addition,
      nitrilase activity was increased suggesting a turnover via nitriles and
      carboxylic acids. Internal degradation of glucosinolates might also be involved
      in diurnal or developmental adaptations of the glucosinolate profile. We observed
      a diurnal rhythm for myrosinase activity in two-week-old plants. Furthermore,
      leaf myrosinase activity and protein abundance of TGG2 varied during plant
      development, whereas leaf protein abundance of TGG1 remained stable indicating
      regulation at the transcriptional as well as post-translational level.

PMID- 30092104
TI  - HIV testing during pregnancy for prevention of mother-to-child transmission of
      HIV in Ethiopia.
AB  - INTRODUCTION: HIV testing during pregnancy provides an entry point to prevention
      of mother-to-child transmission of HIV and to access treatment for HIV positive
      women. The study aimed to assess the uptake of HIV testing during pregnancy and
      associated factors among Ethiopian women. METHODS: We analyzed the 2016 Ethiopian
      Demographic and Health Survey dataset. Women who gave birth within one year prior
      to the survey were included in the analysis. Uptake of HIV testing during
      pregnancy is defined as receiving HIV testing service during pregnancy and/or at
      the time of delivery and knew the test results. Adjusted odds ratios (AORs) and
      95% confidence intervals (95% CIs) were calculated by using step-wise backward
      logistic regression analyses to identify factors associated with HIV testing
      during pregnancy. RESULTS: A total of 2114 women who were pregnant in the last
      one year prior to the survey were included in the analysis. Of these, only 35.1%
      were tested for HIV and received the test results during pregnancy. About one
      third of women who had antenatal care follow-up missed the opportunity to be
      tested for HIV. Compared to women who had no formal education, those who had
      primary level education (AOR = 1.55; 95% CI: 1.12-2.15), secondary level
      education (AOR = 2.56 95%CI: 1.36-3.82), or higher education (AOR = 3.95, 95%CI:
      1.31-11.95) were more likely to be tested for HIV during pregnancy. Similarly,
      having awareness about mother-to-child transmission of HIV (AOR = 2.03, 95%CI:
      1.48-2.78), and living in urban areas (AOR = 3.30, 95%CI: 1.39-7.85) were
      positively and independently associated with uptake of HIV during pregnancy.
      Women who have stigmatizing attitude towards HIV positive people were less likely
      to be tested for HIV (AOR = 0.57, 95%CI: 0.40-0.79). CONCLUSION: Uptake of HIV
      testing during pregnancy is low. Missed opportunity among women who had antenatal
      care visits was very high. Integrating HIV testing with antenatal care services,
      improving HIV testing service quality and access are essential to increase uptake
      of HIV testing during pregnancy and reach the goal of eliminating MTCT.

PMID- 30092105
TI  - The effect of maternal NODAL on STOX1 expression in extravillous trophoblasts is
      mediated by IGF1.
AB  - The number of molecules identified to be involved in communication between
      placenta and decidua is fast expanding. Previously, we showed that NODAL
      expressed in maternal endometrial stromal cells is able to affect NODAL and STOX1
      expression in placental extravillous trophoblasts. The effect of maternal NODAL
      on placental NODAL expression is achieved via Activin A, while preliminary data
      suggests that maternal NODAL affects STOX1 expression in trophoblasts potentially
      via IGF1. In the current study, T-HESC endometrial stromal cells were treated
      with siRNAs against NODAL after which IGF1 mRNA expression was determined by
      quantitative RT-PCR, while IGF1 secretion was measured by ELISA. Recombinant IGF1
      and inhibitors of the MAPK and PI3K/AKT pathways were added to SGHPL-5
      extravillous trophoblasts after which the effects on STOX1 mRNA and STOX1 protein
      expression were determined. The effect of IGF1 and the MAPK and PI3K/AKT
      inhibitors on the invasive capacity of SGHPL-5 cells was investigated by
      performing invasion assays. We found that T-HESC cells treated with NODAL siRNAs
      showed significant upregulation of IGF1 mRNA expression and IGF1 protein
      secretion. Addition of IGF1 to SGHPL-5 cell media significantly upregulated STOX1
      mRNA and protein expression. Using inhibitors of the PI3K/AKT and MAPK pathway
      showed that the effect of IGF1 on STOX1 expression is accomplished via MAPK
      signaling. Secondly, PI3K inhibition independently leads to reduced STOX1
      expression which can be rescued by adding IGF1. IGF1 was unable to influence the
      invasive capacity of SGHPL-5 cells, while inhibiting the PI3K/AKT pathway did
      reduce the invasion of these cells. To conclude, here we show that downregulated
      NODAL expression in endometrial stromal cells, previously associated with pre
      eclampsia like symptoms in mice, increases IGF1 secretion. Increased levels of
      IGF1 lead to increased expression levels of STOX1 in extravillous trophoblasts
      via the MAPK pathway, hereby identifying a novel signaling cascade involved in
      maternal-fetal communication.

PMID- 30092107
TI  - Pediatric Pelvic Ring Injuries.
AB  - The purpose of this study was to determine whether pelvic fracture pattern is
      associated with transfusion requirements or concomitant injuries in pediatric
      patients. This was a single-institution, retrospective review from 1970 to 2000.
      Pelvic ring injuries were classified using the Orthopaedic Trauma Association
      system. Injury Severity Scores were assigned. Ninety patients were included in
      this study. There were 27 A-type (30.0%), 51 B-type (56.7%), and 12 C-type
      (13.3%) injuries. Mean Injury Severity Scores were 8.1 for 61 A-type, 12.7 for 61
      B-type, and 23.6 for 61 C-type fractures (P<.0001). Transfusion was required for
      14.8% of A-type, 18.4% of B-type, and 66.7% of C-type injuries (P=.0009). There
      was no significant association with the number of units transfused (P=.9614).
      Decreased pelvic ring fracture stability was associated with an increased need
      for blood transfusion, although not with the number of units. Pelvic ring
      fracture stability may be a marker of associated injuries. [Orthopedics. 2018;
      41(5):e701-e704.].

PMID- 30092108
TI  - A Novel Medial Collateral Ligament Reconstruction Technique Using Internally
      Braced Semitendinosus Autograft.
AB  - Medial collateral ligament reconstruction is often performed in knees with
      multiligamentous injury, and numerous techniques have been previously described.
      A novel method of internally bracing and reconstructing the medial collateral
      ligament with a semitendinosus autograft is described. This provides several
      advantages, including reproducible isometric graft placement, optimized fixation
      strength, and internal bracing. [Orthopedics. 2018; 41(5):e738-e740.].

PMID- 30092106
TI  - Maternal omega-3 polyunsaturated fatty acid supplementation on offspring hip
      joint conformation.
AB  - Unsaturated omega-3 fatty acids, especially docosahexaenoic acid (DHA), when fed
      to dogs improves cognitive and neurological development. Supplementation with
      omega-3 fatty acids such as DHA and eicosapentaenoic acid (EPA) has also been
      associated with lipid peroxidation, which in turn has been implicated in reduced
      body weight and altered bone formation. To assess the impact of omega-3 fatty
      acid supplementation on skeletal growth, diets containing three levels of DHA and
      EPA (0.01 and 0.01%, 0.14 and 0.12%, and 0.21 and 0.18%, respectively) were fed
      to bitches during gestation and lactation with puppies also supplemented through
      weaning. Thus, the subjects studied were the puppies supplemented with DHA and
      EPA through gestation and early postnatal life. The hip joint conformation of the
      puppies (n = 676) was recorded at adulthood using two radiographic, non-invasive
      evaluations. In this population, females had higher hip distraction indices (DI)
      than males. Males from the lower two levels of DHA and EPA supplementation had
      significantly smaller hip DI than all females and males from the highest DHA and
      EPA supplementation. In contrast, there were no diet effects on anatomical
      indicators of hip joint conformation and no visible arthritic changes. These data
      suggest that dietary supplementation of DHA and EPA during gestation and the
      perinatal period to weaning does not adversely influence hip joint formation of
      dogs.

PMID- 30092109
TI  - Overlapping Lower Extremity Total Joint Arthroplasty Does Not Increase the Risk
      of 90-Day Complications.
AB  - Although total hip arthroplasty and total knee arthroplasty commonly overlap,
      there are concerns about the safety and quality of this scenario. The objectives
      of this study were to (1) compare the operative time and the incidence of 90-day
      complications between overlapping and nonoverlapping total joint arthroplasties;
      and (2) evaluate the effect of the duration of overlap on operative time and the
      incidence of 90-day complications. A total of 9192 patients who underwent primary
      total hip arthroplasty or total knee arthroplasty at a large academic hospital
      from 2005 to 2014 were identified. A surgery was defined as overlapping if it had
      an incision to closure overlap time of at least 1 minute with any other surgery
      performed by the same surgeon. A total of 2669 (29%) patient procedures were
      classified as overlapping. Operative times and 90-day complications were compared
      between overlapping and nonoverlapping surgeries. Mixed effects regression models
      were used to assess the independent effects of overlapping surgeries. After
      adjusting for baseline characteristics, operative times were longer for the
      overlapping surgery group (P<.001). Overlapping surgeries had fewer
      thromboembolic events (P=.003) and periprosthetic joint infections (P=.039).
      Wound dehiscence (P=.662), superficial infection (P=.161), and wound hematoma
      (P=.511) were similar between the 2 groups. Operative times increased with
      increasing duration of overlap (P<.001); however, there was no association
      between duration of overlap and 90-day complications (P>.05 for all). Although
      overlapping surgeries had increased operative times, they did not appear to
      increase the risk of perioperative complications. This information may be helpful
      for scheduling overlapping procedures and counseling patients. [Orthopedics.
      2018; 41(5):e695-e700.].

PMID- 30092110
TI  - Potential Usefulness of Losartan as an Antifibrotic Agent and Adjunct to Platelet
      Rich Plasma Therapy to Improve Muscle Healing and Cartilage Repair and Prevent
      Adhesion Formation.
AB  - Postoperative tissue fibrosis represents a major complication in orthopedics.
      Transforming growth factor beta 1 is a key molecule in the development of
      postoperative fibrosis. High concentrations of transforming growth factor beta 1
      have also been implicated in various diseases. Agents that counteract the actions
      of transforming growth factor beta 1 have been investigated as potential
      antifibrotic medications and as adjunct treatment to platelet-rich plasma
      injections (increased amounts of transforming growth factor beta 1) to improve
      their effectiveness and/or safety profile. Losartan blocks transforming growth
      factor beta 1 action and has attracted special interest in orthopedic research
      that focuses on how to reduce the risk of postoperative fibrosis. [Orthopedics.
      2018; 41(5):e591-e597.].

PMID- 30092111
TI  - The Use of Triphasic Bone Graft for the Treatment of Pediatric Bone Cysts:
      Experience at 2 Institutions.
AB  - Unicameral/aneurysmal bone cysts can lead to pain, fracture, and limb deformity.
      In this study, the authors evaluated the outcome of triphasic bone graft to treat
      unicameral/aneurysmal bone cysts. They retrospectively evaluated 41 immature
      patients from a prospectively enrolled cohort from 2 institutions treated from
      May 9, 2007, to November 1, 2014. Medical record review and evaluation of
      radiographs and computed tomography scans were performed. The authors
      characterized replacement of the material by normal bone or recurrent cyst at
      final follow-up. They recorded rates of fractures and complications after
      treatment. Twenty-nine patients were treated in Wisconsin, and 12 patients were
      treated in Florida. Average follow-up was 2.8 years. At follow-up, 13 of 41
      patients had cyst recurrence. Three patients had fracture after initial
      treatment; 2 were treated surgically. Two of 9 patients with extraosseous bone
      graft had soft tissue swelling, and 1 required debridement. Complications did not
      differ by cyst type, location, sex, age, or use of internal fixation. For 27
      patients with at least 2-year follow-up, percent fill of triphasic bone graft at
      initial surgery correlated with rate of recurrence at final follow-up: 15 of 27
      patients with no cyst recurrence at final follow-up had a mean of 100% initial
      fill, and 12 of 27 with cyst recurrence at final follow-up had a mean of 90%
      initial fill (P=.048). Using triphasic bone graft for the treatment of
      unicameral/aneurysmal bone cysts, the authors observed a 7% rate of clinical
      recurrence (3 of 41 had fracture). Because this material has the potential to be
      locally inflammatory, efforts are needed to keep it within the bone.
      [Orthopedics. 2018; 41(5):e705-e712.].

PMID- 30092112
TI  - Minimum 10-Year Clinical Outcomes After Periacetabular Osteotomy for Advanced
      Osteoarthritis Due to Hip Dysplasia.
AB  - The purpose of this study was to examine the minimum 10-year clinical outcomes,
      including patient-reported and functional outcomes, of periacetabular osteotomy
      in patients with advanced osteoarthritis. A total of 46 hips in 44 patients with
      advanced osteoarthritis who underwent periacetabular osteotomy between 1992 and
      2006 were retrospectively reviewed. Mean age at surgery was 47.5 years, and mean
      follow-up was 16.9+/-4.7 years. Survivorship was determined using the Kaplan
      Meier method, and the associated risk factors for the endpoint-conversion to
      total hip arthroplasty less than 15 years after surgery-were evaluated. The
      Oxford Hip Score and the University of California, Los Angeles activity score
      were evaluated at final follow-up. The survival rates at 15 and 20 years after
      surgery were 80% and 59%, respectively. Multivariate analysis indicated that body
      mass index greater than 24 kg/m2 (P=.034; odds ratio, 1.72) was significantly
      associated with the endpoint as an independent risk factor. For 32 hips of 31
      patients with preserved native joints at final follow-up, the Oxford Hip Score
      and the University of California, Los Angeles score averaged 41+/-5 and 5.2+/
      1.8, respectively, equivalent (P=.28 and P=.215, respectively) to the scores of
      14 hips of 13 patients with conversion to total hip arthroplasty (38+/-8.7 and
      5.8+/-1.4, respectively). The results of this mid-term study may be useful for
      surgical decision-making among patients with advanced osteoarthritis who want to
      preserve native hip joints. [Orthopedics. 2018; 41(5):300-305.].

PMID- 30092113
TI  - Different dimensions of religiousness/spirituality are associated with health
      behaviors in breast cancer survivors.
AB  - OBJECTIVE: Religiousness/spirituality (R/S) may influence cancer survivors'
      health through multiple pathways. We aimed to examine one potentially key pathway
      that has seldom been examined: relationships between survivors' R/S and their
      health behaviors. METHODS: The present study investigated links between four core
      dimensions of R/S (beliefs, behaviors, identity, and coping) and three health
      behaviors (fruit/vegetable consumption, physical activity, and maintenance of a
      healthy weight) in 172 breast cancer survivors. RESULTS: Both spiritual identity
      and use of religious coping were positively related to fruit and vegetable
      intake, while private prayer was marginally positively related. Both service
      attendance and religious identity (marginally) were related to engaging in less
      physical activity, while private prayer was positively related. Afterlife beliefs
      and private prayer were positively associated with BMI. CONCLUSIONS: R/S has
      complex but meaningful associations with health behaviors in breast cancer
      survivors. More research is needed to understand these relationships and to
      determine whether different dimensions of R/S may play useful roles in lifestyle
      change interventions.

PMID- 30092114
TI  - Heat shock protein 47 as indispensible participant in liver fibrosis: Possible
      protective effect of lactoferrin.
AB  - Lactoferrin (LF) was previously suggested to have a protective effect against
      liver fibrosis by preventing hepatic stellate cells (HSCs) activation. The effect
      of LF on heat shock protein 47 (HSP47) has not yet been studied so this study was
      designed to investigate LF effect on HSP47 as a potential target for management
      of liver fibrosis and comparing it with silymarin (SM) in a thioacetamide (TAA)
      induced liver fibrosis model. Rats were divided into four groups; normal control,
      TAA (TAA-treated), LF (LF + TAA-treated), and SM (SM + TAA-treated). After 6
      weeks, both LF and SM improved the grade of cirrhosis, reduced collagen fibers
      deposition, inactivated HSCs, significantly decreased elevated liver enzymes,
      HSP47, hydroxyproline content, transforming growth factor-beta 1, matrix
      metalloproteinase-2, 8-hydroxydeoxyguanosine, malondialdehyde, nitric oxide
      levels and the percentage of alpha smooth muscle actin positive HSCs compared
      with TAA group. Moreover, LF significantly increased the total antioxidant
      capacity compared with TAA group. It could be concluded that LF is a promising
      antifibrotic drug and could be considered as one of the HSP47 inhibitors but SM
      is still more potent. (c) 2018 IUBMB Life, 70(8):795-805, 2018.

PMID- 30092115
TI  - Influence of soft tissue grafting, orofacial implant position, and angulation on
      facial hard and soft tissue thickness at immediately inserted and provisionalized
      implants in the anterior maxilla.
AB  - BACKGROUND: Resorption of hard and soft tissues following immediate implant
      insertion is frequently reported. Data regarding the influencing factors on
      facial tissue thickness are rare. PURPOSE: This retrospective study investigated
      the impact of connective tissue grafting, the orofacial angulation and position
      of immediately inserted and provisionalized implants on the facial hard and soft
      tissue thickness in the anterior maxilla within a 1- to 5-year follow-up.
      MATERIAL AND METHODS: Implants with the prerequisite of having preoperative and
      postoperative cone beam computed tomography (CBCT) and a follow-up of 1 to 5
      years were included. Facial bone deficiencies were grafted flaplessly with
      autogenous bone in all sites. In a subgroup of implants additional connective
      tissue grafting was performed, whereas the remaining implants were not grafted
      with soft tissue. The orofacial tooth and implant angulation, the change of
      horizontal position and the facial bone thickness were measured by CBCT, the
      facial mucosa thickness by an ultrasonic device. RESULTS: In total, 76 implants
      were placed in 55 patients. Sixty-nine sites showed a facial bone defect. Thirty
      eight received a connective tissue graft additionally. All implants were still in
      function after a mean follow-up of 36 months. The mean thickness of the facial
      mucosa was 1.72 mm at 1 mm, 1.63 mm at 4 mm, 1.52 mm at 6 mm, and 1.66 mm at 9 mm
      apically to mucosal margin. The bone thickness was 0.02, 0.25, and 0.36 mm
      initially and 1.32, 1.26, and 1.11 mm finally at 1, 3, and 6 mm apically to
      implant shoulder level. Mixed model analysis revealed an impact of the
      preoperative bone status on the facial bone increase. The facial soft tissue
      thickness was significantly influenced by the gingival biotype. CONCLUSIONS: The
      results indicate that an initial severe hard tissue defect allows for significant
      bone regeneration. The facial soft tissue thickness is primarily influenced by
      the gingival biotype.

PMID- 30092116
TI  - Mass spectrometry-based proteomic analysis reveals the interacting partners of
      lipin1.
AB  - As a lipin family founding member, lipin1 exerts dual functions as a
      phosphatidate phosphatase enzyme and/or a co-transcriptional regulator in lipid
      metabolism. In fact, it is also involved in many other cell processes. In this
      study, we utilized pull down assay coupled with mass spectrometry (MS) to unravel
      protein-protein interaction networks of lipin1 in 293T human embryonic kidney
      cells. Pull-down assay on the Ni2+ -chelating column was used to isolate lipin1
      complexes from 293T cells transfected with 6-His tagged lipin1. The lipin1
      complexes were analyzed on Q Exactive mass spectrometer. A total of 30 proteins
      were identified from label free quantitation of the MS data by Proteome
      Discoverer platform. The physical interaction between lipin1 and eEF1A1 was
      further affirmed in 293T cells transfected with 6-His tagged lipin1 and
      hepatocyte SMMC7721 cells by protein immunoprecipitation and immunofluorescence
      microscopy. Lipin1 also interacted with HIST1H2BK, which was confirmed in
      SMMC7721 cells by protein immunoprecipitation. Our proteomic analysis implicated
      lipin1 in novel roles in various cellular processes. (c) 2018 IUBMB Life,
      70(8):753-762, 2018.

PMID- 30092117
TI  - Elucidating the role of (p)ppGpp in mycobacterial persistence against
      antibiotics.
AB  - Bacterial persistence, the ability of bacteria to survive high concentrations of
      antibiotics for extended periods of time, is an important contributing factor to
      therapy failure and development of chronic and recurrent infections. Several
      recent studies have suggested that this persistence is mediated primarily by
      (p)ppGpp, through its interactions with toxin-antitoxin modules and
      polyphosphates. In this study, we address whether these key players play a role
      in mycobacterial persistence against antibiotics. We targeted these specific
      pathways in Mycobacterium smegmatis by constructing deletion strains of (p)ppGpp
      synthetase/hydrolase (relA), polyphosphate kinases (ppk1 and ppk2),
      exopolyphosphatases (ppx1 and ppx2), and the lon protease. None of these mutant
      strains exhibited altered levels of persisters against isoniazid and
      ciprofloxacin, when compared with wild-type strain. Even under conditions in
      which the stringent response usually gets activated, these strains displayed wild
      type persister levels. Interestingly, we also found that unlike Escherichia coli,
      maintaining M. smegmatis in exponential phase by repeated passaging does not
      eliminate persisters suggesting that at least against the antibiotics tested,
      stationary-phase dependent persisters (type I) are not the major contributors.
      Thus, our data demonstrate that multiple mechanisms of antibiotic persistence
      exist and that these vary widely among different bacterial species. (c) 2018
      IUBMB Life, 70(9):836-844, 2018.

PMID- 30092118
TI  - Metabolomic study for essential hypertension patients based on dried blood spot
      mass spectrometry approach.
AB  - Hypertension is an increasingly serious public-health challenge worldwide. The
      traditional blood pressure measurement method could easily and reliably detect
      blood pressure. However, the delayed symptom onset may influence the screening of
      essential hypertension (EH). In addition, EH is significantly associated to
      cardiovascular disease, stroke and kidney disease. Hence, it is urgent to define
      associated biomarkers with early diagnosis potential for EH. A dried blood spot
      method integrated with direct infusion mass spectrometry (MS) metabolomic
      analysis was applied for the detection of metabolites toward 87 EH patients and
      91 healthy controls (HC). Multiple algorithms were run on training set (62 EH and
      64 HC) for selecting differential metabolites as potential biomarkers. A test set
      (25 EH and 27 HC) was used to verify and evaluate selected potential biomarkers.
      A novel blood biomarker model based on Gly, Orn, C10, Orn/Cit, Phe/Tyr, and C5
      OH/C8 exhibited potential to differentiate EH patients from HC individuals, with
      a sensitivity of 0.8400 and a specificity of 0.8889 in test set. The metabolomic
      analysis of EH is beneficial to the definition of disease-associated biomarkers
      and the development of new diagnostic approaches. (c) 2018 IUBMB Life, 70(8):777
      785, 2018.

PMID- 30092119
TI  - Cation-Anion-CO2 Interactions in Imidazolium-Based Ionic Liquid Sorbents.
AB  - A series of functionalized N-alkylimidazolium based ionic liquids (ImILs) were
      designed, through anion (carboxylates and halogenated) and cation (N-alkyl side
      chains) structural modifications, and studied as potential sorbents for CO2 . The
      sorption capacities of as prepared bare ImILs could be enhanced from 0.20 to 0.60
      molar fraction by variation of cation-anion-CO2 and IL-CO2 -water interaction. By
      combining NMR spectroscopy with molecular dynamics simulations, a good
      description of interactions between ImIL and CO2 can be obtained. Three types of
      CO2 sorption modes have been evidenced depending on the structure of the ImIL ion
      pair: Physisorption, formation of bicarbonate, and covalent interaction through
      the nucleophilic addition of CO2 to the cation or anion. The highest CO2 sorption
      capacity was observed with the ImIL containing the 1-n-butyl-3-methylimidazolium
      cation associated with the carboxylate anions (succinate and malonate). This
      study provides helpful clues for better understanding the structure-activity
      relationship of this class of materials and the ion pair influence on CO2
      capture.

PMID- 30092120
TI  - Participation in a prostate cancer support group and health literacy.
AB  - BACKGROUND: To cope with prostate cancer (PC) and its consequences and to be
      certain about therapeutic alternatives, some patients seek mutual help in
      prostate cancer support groups (PCSGs), where they share information and find
      social support. Our study was intended to assess whether group participation is
      associated with health literacy (HL). METHODS: We compared PCSG members (n = 441)
      with PC patients without support group experiences (n = 135) in a cross-sectional
      design. For this purpose, HL was operationalized through PC-specific knowledge,
      noncancer-specific knowledge about health care, guideline awareness, and skills
      needed to apply health information to meet own needs. Binary logistic regression
      models were calculated. Socio-demographic data and disease-related
      characteristics were used as control variables. RESULTS: Knowledge about PC (OR,
      2.2; CI, 1.3-3.7), the fact of having heard of guidelines (OR, 3.7; CI, 2.1-6.8)
      and having read one (OR, 5.1; CI, 2.8-9.4), and competencies regarding health
      service navigation (OR, 1.8; CI, 1.0-3.1) are associated with PCSG membership. No
      statistically significant associations could be found between PCSG membership and
      further skills questioned, as well as between membership and knowledge about
      noncancer-specific health care. CONCLUSION: PCSG membership is associated with HL
      in some areas only. In particular, the groups seem to provide an important
      platform for information exchange in the field of PC. The potentially conflicting
      results on PC knowledge and the application skills may arise from the different
      forms of measurement-knowledge was tested; skills were self-assessed.

PMID- 30092121
TI  - Removal of Intrathecal Catheters Used in Drug Delivery Systems.
AB  - INTRODUCTION: Implanted intrathecal drug delivery systems (IDDS) are increasingly
      used in the treatment of spasticity and in patients with refractory pain.
      Literature discussing complications associated with intrathecal pump placement is
      widely available. However, reports of complications following the removal of
      chronically placed catheters are scarce. We reviewed our series of patients who
      had surgery to remove the intrathecal catheter. METHODS: Retrospective review was
      performed for all patients who underwent surgery to remove a catheter linked to
      an IDDS between 2010 and 2016. Patients older than 18 years were included in
      final analysis. Demographic (including age at removal, sex, BMI, and
      comorbidities) and etiologic characteristics (indications of IDDS implant and
      explant, interval between implant and explant, and concomitant surgery) were
      analyzed. Simple logistic regression was performed to seek any potential
      predictor of complications. RESULTS: Fifty-nine patients underwent removal of
      their intrathecal catheter after variable periods (mean interval of 189 months).
      On eight occasions, patients developed complications after catheter removal (mean
      interval between implant and explant was 76 months for these cases). Retained
      catheter was the cause of complications in half of these occasions. Persistent
      cerebrospinal fluid leak was the next most common complication, with requirement
      of an external ventricular drain and lumbar drain to facilitate wound healing on
      two separate occasions. CONCLUSION: Removal of an intrathecal catheter from IDDS
      systems may cause complications that in some cases require additional surgery.

PMID- 30092123
TI  - Postfunctionalization of Tris(pyridyl) Aluminate Ligands: Chirality,
      Coordination, and Supramolecular Chemistry.
AB  - Postfunctionalization of the aluminate anion [EtAl(6-Me-2-py)3 ]- (1) (2-py=2
      pyridyl) with alkoxide ligands can be achieved by the selective reactions of the
      lithium salt 1 Li with alcohols in the appropriate stoichiometry. This method can
      be used to introduce 3- and 4-py functionality in the form of 3- and 4
      alkoxymethylpyridyl groups, while maintaining the integrity of the aluminate
      framework, thereby giving entry to new supramolecular chemistry. Chirality can be
      introduced either by using a chiral alcohol as a reactant or by the stepwise
      reaction of 1 Li with two different nonchiral alcohols. The latter route has
      allowed the synthesis of a rare example of a chiral-at-aluminium aluminate.

PMID- 30092124
TI  - Unique Stereoselective Homolytic C-O Bond Activation in Diketopiperazine-Derived
      Alkoxyamines by Adjacent Amide Pyramidalization.
AB  - Simple monocyclic diketopiperazine (DKP)-derived alkoxyamines exhibit
      unprecedented activation of a remote C-O bond for homolysis by amide distortion.
      The combination of strain-release-driven amide planarization and the persistent
      radical effect (PRE) enables a unique, irreversible, and quantitative trans->cis
      isomerization under much milder conditions than typically observed for such
      homolysis-limited reactions. This isomerization is shown to be general and
      independent of the steric and electronic nature of both the amino acid side
      chains and the substituents at the DKP nitrogen atoms. Homolysis rate constants
      are determined, and they significantly differ for both the labile trans
      diastereomers and the stable cis diastereomers. To reveal the factors influencing
      this unusual process, structural features of the kinetic trans diastereomers and
      thermodynamic cis diastereomers are investigated in the solid state and in
      solution. X-ray crystallographic analysis and computational studies indicate
      substantial distortion of the amide bond from planarity in the trans
      alkoxyamines, and this is believed to be the cause for the facile and
      quantitative isomerization. Thus, these amino-acid-derived alkoxyamines are the
      first examples that exhibit a large thermodynamic preference for one diastereomer
      over the other upon thermal homolysis, and this allows controlled switching of
      configurations and configurational cycling.

PMID- 30092125
TI  - Mental health and reactions to caregiving among next of kin of older people (65+)
      with multi-morbidity discharged home after hospitalization.
AB  - BACKGROUND: Older people with multi-morbidity are major users of healthcare and
      are often discharged from hospital with ongoing care needs. This care is
      frequently provided by informal caregivers and the time immediately after
      discharge is challenging for caregivers with new and/or additional tasks,
      resulting in anxiety and stress. AIM: This study aimed to describe mental health,
      with particular reference to anxiety and depression and reactions to caregiving,
      and to investigate any associations between the two, in next of kin of older
      people with multi-morbidity after hospitalisation. It also aimed to explore the
      association between the demographic characteristics of the study group and mental
      health and reactions to caregiving. METHODS: This was a cross-sectional
      questionnaire study using the Hospital Anxiety and Depression Scale and the
      Caregiver Reaction Assessment. The study group consisted of 345 next of kin of
      older people (65+) with multi-morbidity discharged home from 13 medical wards in
      Sweden. Data were analysed using descriptive and analytical statistics. To
      identify whether reactions to caregiving and next of kin characteristics were
      associated with anxiety and depression, a univariate logistic regression analysis
      was performed. RESULTS: More than one quarter of respondents showed severe
      anxiety and nearly one in 10 had severe depressive symptoms. The frequencies of
      anxiety and depression increased significantly with increased negative reactions
      to caregiving and decreased significantly with positive reactions to caregiving.
      Regarding caregiving reactions, the scores were highest for the positive domain
      Caregiver esteem, followed by the negative domain Impact on health. Women scored
      significantly higher than men on Impact on health and spouses scored highest for
      Impact on schedule and Caregiver esteem. CONCLUSIONS: Nurses and other healthcare
      professionals may need to provide additional support to informal caregivers
      before and after discharging older people with significant care needs from
      hospital. This might include person-centred information, education and training.

PMID- 30092122
TI  - Peptide nucleic acid (PNA) probe-based analysis to detect filaggrin mutations in
      atopic dermatitis patients.
AB  - Atopic dermatitis (AD) is a chronic inflammatory skin disease whose prevalence is
      increasing worldwide. Filaggrin (FLG) is essential for the development of the
      skin barrier, and its genetic mutations are major predisposing factors for AD. In
      this study, we developed a convenient and practical method to detect FLG
      mutations in AD patients using peptide nucleic acid (PNA) probes labelled with
      fluorescent markers for rapid analysis. Fluorescence melting curve analysis
      (FMCA) precisely identified FLG mutations based on the distinct difference in the
      melting temperatures of the wild-type and mutant allele. Moreover, PNA probe
      based FMCA easily and accurately verified patient samples with both heterozygote
      and homozygote FLG mutations, providing a high-throughput method to reliable
      screen AD patients. Our method provides a convenient, rapid and accurate
      diagnostic tool to identify potential AD patients allowing for early preventive
      treatment, leading to lower incidence rates of AD, and reducing total healthcare
      expenses.

PMID- 30092126
TI  - Novel compound heterozygous ABCC2 variants in patients with Dubin-Johnson
      syndrome and intrahepatic cholestasis of pregnancy.

PMID- 30092127
TI  - [MINI-PERCUTANEOUS NEPHROLITHOTRIPSY - OUR FIRST EXPERIENCE].
AB  - Urolithiasis is a significant problem in the developed countries due to the
      increased number of patients with stones. Just a few decades ago open surgery was
      the only surgical treatment which is today, in most cases, replaced with
      minimally-invasive methods. One of these new methods is mini-percutaneous
      nephrolihotripsy. We present  four patients in whom mini-percutaneous
      nephrolithotripsy was performed. In all patients the stone was located in the
      renal pelvis. In three patients the stone was in the native kidney and in one in
      the transplanted kidney. In all patients laser lithotripsy was successfully
      performed. On the control x-ray the residual fragments were not found in any
      patients. Mini-percutaneous nephrolithotripsy is a minimally-invasive method
      which is successfull in the treatment of nephfrolithiasis in native and
      transplanted kidneys.

PMID- 30092128
TI  - Vitamin E d-alpha-Tocopheryl Polyethylene Glycol Succinate (TPGS) Provokes Cell
      Death in Human Neuroblastoma SK-N-SH Cells via a Pro-Oxidant Signaling Mechanism.
AB  - Neuroblastoma (NB) is the most common neoplasm during infancy. Unfortunately, NB
      is still a lethal cancer. Therefore, innovative curative therapies are
      immediately required. In this study, we showed the prodeath activity of TPGS in
      human NB SK-N-SH cancer cells. NB cells were exposed to TPGS (10-80 MUM). We
      report for the first time that TPGS induces cell death by apoptosis in NB cells
      via a pro-oxidant-mediated signaling pathway. Certainly, H2O2 directly oxidizes
      DJ-1 cysteine106-thiolate into DJ-1 cysteine106-sulfonate, indirectly activates
      the transcription factors NF-kappaB, p53, and c-JUN, induces the upregulation of
      mitochondria regulator proteins BAX/PUMA, and provokes the loss of mitochondrial
      membrane potential (DeltaPsim) and the activation of caspase-3/AIF, leading to
      nuclear disintegration, demonstrated by cellular and biochemical techniques such
      as fluorescence microscopy, flow cytometry, and Western blot analysis. Since TPGS
      is a U.S. Food and Drug Administration (FDA)-approved pharmaceutical excipient,
      this molecule might be used in clinical trials for NB treatment.

PMID- 30092131
TI  - Naked pDNA inhalation powder composed of hyaluronic acid exhibits high gene
      expression in the lungs.
AB  - Gene therapy is a breakthrough treatment strategy against several intractable and
      lethal diseases that previously lacked established treatments. Viral and non
      viral vectors have been studied to realize higher gene transfection efficiencies
      and to suppress the degradation of gene by nucleolytic enzymes in vivo. However,
      it is often the case that the addition of a vector results in adverse effects. In
      this study, we identified formulations of dry naked plasmid DNA (pDNA) powders
      with no vector showing significantly higher gene expression than pDNA solutions
      including vectors such as polyethylenimine (PEI) in the lungs of mice. We
      prepared the naked pDNA powders by spray-freeze-drying with various excipients.
      The gene expression of naked pDNA powders exceeded those of pDNA solutions
      containing PEI, naked pDNA solution, and reconstituted pDNA powder. Gene
      expression of each naked pDNA powder was dependent on the composition of
      excipients. Among them, the mice administered to the pDNA powder composed of low
      molecular-weight hyaluronic acid (LHA) as an excipient showed the highest gene
      expression. The lactate dehydrogenase activity and concentration of inflammatory
      cytokines in bronchoalveolar lavage fluid were comparable to those caused by
      ultra-pure water. The results suggest that useful dry naked nucleic acid powders
      for inhalation could be created by optimizing the excipients, offering new
      insights into the development of pulmonary gene therapy.

PMID- 30092130
TI  - C-H Functionalization of Heteroarenes Using Unactivated Alkyl Halides through
      Visible-Light Photoredox Catalysis under Basic Conditions.
AB  - C-H functionalization of electron-deficient heteroarenes using commercial
      unactivated alkyl halides through reductive quenching photoredox catalysis was
      developed. Mainstream approaches rely on the use of an excess of strong acids
      that result in regioselectivities dictated by the innate effect of the protonated
      heteroarene, leaving the functionalization of other carbons unexplored. We report
      a mild method under basic conditions that allows access to previously
      underexplored regioselectivities by relying on a combination of conjugate and
      halogen  ortho-directing effects. Overall, this methodology gives quick access to
      a variety of alkylated heteroarenes that will be of interest to medicinal
      chemistry programs.

PMID- 30092129
TI  - Knockout of SlMAPK3 Reduced Disease Resistance to Botrytis cinerea in Tomato
      Plants.
AB  - Mitogen-activated protein kinases (MAPKs) play an important role in defense
      responses to biotic and abiotic stresses. In order to investigate the role of
      SlMAPK3 in tomato plant resistance to Botrytis cinerea, two lines of slmapk3
      mutants and wild-type (WT) tomato plants were used. The results showed that
      slmapk3 mutants were more susceptible to B. cinerea and that knockout of SlMAPK3
      reduced the activities of defense enzymes and enhanced the accumulation of
      reactive oxygen species (ROS). Furthermore, we detected the expressions of
      salicylic acid (SA) and jasmonic acid (JA) signaling-related genes and found that
      knockout of SlMAPK3 enhanced the expressions of SlPR1, SlPAD4 and SlEDS1, whereas
      reduced the expressions of SlLoxC, SlPI I and SlPI II and enhanced the
      expressions of SlJAZ1 and SlMYC2. We postulate that SlMAPK3 plays a positive role
      in tomato plant resistance to B. cinerea through regulating ROS accumulation and
      SA and JA defense signaling pathways.

PMID- 30092132
TI  - A New Microchip Design. A Versatile Combination of Electromembrane Extraction and
      Liquid-Phase Microextraction in a Single Chip Device.
AB  - For the first time, a novel and versatile microfluidic device was developed to
      achieve the possibility of combining different extraction principles using a
      miniaturized approach for the extraction of different classes of analytes. This
      novel microchip is composed of a sandwich of three poly(methyl methacrylate)
      (PMMA) layers. Four channels allowed the combination of electromembrane
      extraction (EME) and liquid-phase microextraction (LPME) in three different ways:
      (I) EME and LPME, (II) EME and EME, or (III) LPME and LPME. The microchip can be
      used either (a) using a common acceptor phase (for both extractions) for the
      simultaneous extraction of drugs from different nature in a single step, or (b) a
      common sample solution (for both extractions) and two acceptor solutions for
      simultaneous drug separation. In this work, the performance of this novel
      microchip was demonstrated by simultaneous integration of EME and LPME using a
      common acceptor phase for both extractions. This configuration reduces the time
      of analysis allowing direct analysis in a single chip. The microchip was tested
      for extracting two different classes of analytes: five fluoroquinolones and four
      parabens as model analytes. All effective variables were optimized for EME and
      LPME. Under the optimized conditions, the reusable microchip enables simultaneous
      MU-EME/LPME with extraction efficiencies over 77% in only 8 min extraction and
      sample volume consumption lower than 40 MUL. The optimized procedure was
      successfully applied to urine samples obtaining recoveries over 90% for all
      analytes.

PMID- 30092134
TI  - The Role of Molybdenum Oxysulfide Rings in the Formation of Two-Dimensional
      Molybdenum Disulfide by Powder Vaporization.
AB  - Sulfurization of molybdenum trioxide by elemental sulfur through powder
      vaporization is a common method used for growth of molybdenum disulfide.
      Optimization of complexes between sulfur allotropes and molybdenum species using
      Density Functional Theory has revealed the molecular mechanism of sulfurization.
      Complete sulfurization of molybdenum trioxide to molybdenum disulfide requires at
      least three sets of nucleophilic addition-elimination reactions that generate the
      experimentally observed molybdenum oxysulfide intermediates along the reaction
      pathway. Each nucleophilic addition reaction of a sulfur allotrope to a
      molybdenum species gives rise to a molybdenum oxysulfide ring, which can
      dissociate into a more sulfurized molybdenum intermediate. At the typical growth
      temperatures used in powder vaporization, the equilibrium constants for these
      reactions are essentially unity. Thus, sulfurization is driven by excess sulfur
      and gas flow through the growth furnace.

PMID- 30092135
TI  - Water Distribution System Failure Risks with Increasing Temperatures.
AB  - In the coming decades, ambient temperature increase from climate change threatens
      to reduce not only the availability of water but also the operational reliability
      of engineered water systems. Relatively little is known about how temperature
      stress can increasingly cause hardware components to fail, quality to be
      affected, and service outages to occur. Changes to the estimated-time-to-failure
      of major water system hardware and the probability of quality noncompliance were
      estimated for a modern potable water system that experiences hot summer
      temperatures, similar to Phoenix, AZ, and Las Vegas, NV. A fault tree model was
      developed to estimate the probability that consequential service outages in
      quantity and quality will occur. Component failures are projected to have a
      percent increase of 10-101% in scenarios where peak summer temperature has
      increased from 36 to 44  degrees C, which create the conditions for service
      outages to have a percent increase of 7-91%. Increased service outages due to
      multiple pumping unit failures and water quality noncompliances are the most
      notable concerns for water utilities. The most effective strategies to prevent
      temperature-related failures should focus on monitoring and correcting chlorine
      residual and disinfection byproduct concentration, and on cooling pumping unit
      motors and electronics.

PMID- 30092133
TI  - Changes of Anthocyanin Component Biosynthesis in 'Summer Black' Grape Berries
      after the Red Flesh Mutation Occurred.
AB  - The coloring process of grape flesh is valuable for research and promotion of the
      high nutritional quality of anthocyanins. 'Summer Black' and it is new red flesh
      mutant were used to analyze the changes of anthocyanin biosynthesis during grape
      berry development. Eighteen kinds of anthocyanins were detected in mature berries
      of the two cultivars, but the content of most 3'- and 3',5'-substituted
      anthocyanins was higher in the skin of the mutant. Anthocyanin accumulation
      occurred simultaneously in the skin and flesh of the mutant, and their types and
      content were more abundant in the former. For the mutant, there were only CHS,
      OMT, MYBA3, and MYBPA1 at lower transcriptional level in the flesh during
      veraison when compared with these in the skin, which might be an important factor
      to limit the anthocyanin accumulation in the flesh. The occurrence of red flesh
      might be related the enhancement of anthocyanin biosynthesis in the whole berry.

PMID- 30092136
TI  - Splitting of Hydrogen Sulfide by Group 14 Elements (Si, Ge, Sn, Pb) in Excess
      Argon at Cryogenic Temperatures.
AB  - The water gas reaction C + H2O -> CO + H2 has been employed for centuries;
      however little is known for analogous reaction M + H2S -> MS + H2 (M = Si, Ge,
      Sn, Pb). In addition, this latter reaction is intriguing in its function of
      converting pollutant H2S to clean energy source H2. We report herein the
      reactions of laser-ablated Group 14 atom M (M = Si, Ge, Sn, Pb) with H2S using
      matrix isolation infrared spectroscopy as well as the state-of-the-art quantum
      chemical calculations. Important reactive intermediates HMSH with high active H
      (protonic Hdelta+ and hydridic Hdelta-) are identified. In addition, the reaction
      mechanisms are established for insertion reaction M + H2S -> HMSH, and
      photoinduced H2 elimination reactions of HMSH -> MS+ H2 and H2SiS -> SiS+ H2 in
      low-temperature matrices.

PMID- 30092137
TI  - Oligo(ethylene glycol) Length Effect of Water-Soluble Ru-Based Olefin Metathesis
      Catalysts on Reactivity and Removability.
AB  - A study of reaction kinetics and removal efficiency of a family of ruthenium (Ru)
      based olefin metathesis catalysts containing ethylene-glycol-oligomer-tethered N
      heterocyclic carbene (NHC) ligands has been carried out, with a focus on
      variation of ethylene glycol oligomer length. The length of ethylene glycol
      oligomer was precisely defined by sequential addition of repeating units. Due to
      the dual solubility of ethylene glycol oligomer, the produced catalyst was highly
      soluble in both aqueous and organic solvents (dichloromethane). In aqueous
      solution, the polarity increase with longer ethylene glycol oligomers enhanced
      the reactivity in homogeneous solution. The length of ethylene glycol oligomer
      did not significantly affect olefin metathesis rate in organic solution. Yet the
      removal efficiency of catalyst strongly relies on the length of ethylene glycol
      oligomer. A longer ethylene glycol oligomer demonstrated better catalyst removal
      efficiency. The tested catalyst removal method was aqueous extraction from
      organic solution using its higher water solubility property compared to its lower
      organic solvent (dichloromethane) solubility property. The results obtained from
      the aqueous extraction catalyst removal method demonstrated similar and/or better
      removal rates compared to previously reported host-guest catalyst removal
      methods.

PMID- 30092138
TI  - Seeding Iron Trifluoride Nanoparticles on Reduced Graphite Oxide for Lithium-Ion
      Batteries with Enhanced Loading and Stability.
AB  - Development of electric vehicles and portable electronic devices during the past
      decade calls for lithium-ion batteries (LIBs) with enhanced energy density and
      higher stability. Integration of FeF3 phases and carbon structures leads to
      promising cathode materials for LIBs with high voltage, capacity, and power. In
      this study, FeF3.0.33H2O nanoparticles were synthesized on reduced graphite oxide
      (rGO) nanosheets using an in situ approach. By chemically tuning the interfacial
      bonding between FeF3.0.33H2O and rGO, we successfully achieved high particle
      loading and enhanced cycling stability. Specifically, a discharge capacity of
      ~208.3 mAh g-1 was observed at a current density of 0.5 C. The FeF3.0.33H2O/rGO
      nanocomposites also demonstrate great cycle capability with a reversible
      discharge capacity of 133.1 mAh g-1 after 100 cycles at 100 mA g-1; the capacity
      retention is about 97%. This study provides an alternative strategy to further
      improve the stability and performance of iron fluoride/carbon nanocomposite
      materials for LIB applications.

PMID- 30092139
TI  - Epitaxial Growth of gamma-Cyclodextrin-Containing Metal-Organic Frameworks Based
      on a Host-Guest Strategy.
AB  - A class of metal-organic frameworks (MOFs)-namely CD-MOFs-obtained from natural
      products has been grown in an epitaxial fashion as films on the surfaces of glass
      substrates, which are modified with self-assembled monolayers (SAMs) of gamma
      cyclodextrin (gamma-CD) molecules. The SAMs are created by host-guest
      complexation of gamma-CD molecules with surface-functionalized pyrene units. The
      CD-MOF films have continuous polycrystalline morphology with a structurally out
      of-plane ( c-axial) orientation, covering an area of several square millimeters,
      with a thickness of ~2 MUm. Furthermore, this versatile host-guest strategy has
      been applied successfully in the growth of CD-MOFs as the shell on the curved
      surface of microparticles as well as in the integration of CD-MOF films into
      electrochemical devices for sensing carbon dioxide. In striking contrast to the
      control devices prepared from CD-MOF crystalline powders, these CD-MOF film-based
      devices display an enhancement in proton conductance of up to 300-fold. In
      addition, the CD-MOF film-based device exhibits more rapid and highly reversible
      CO2-sensing cycles under ambient conditions, with a 50-fold decrease in
      conductivity upon exposure to CO2 for 3 s which is recovered within 10 s upon re
      exposure to air.

PMID- 30092140
TI  - Core-Level Binding Energies from GW: An Efficient Full-Frequency Approach within
      a Localized Basis.
AB  - The GW method is routinely used to predict charged valence excitations in
      molecules and solids. However, the numerical techniques employed in the most
      efficient GW algorithms break down when computing core excitations as measured by
      X-ray photoelectron spectroscopy (XPS). We present a full-frequency approach on
      the real axis using a localized basis to enable the treatment of core levels in
      GW. Our scheme is based on the contour deformation technique and allows for a
      precise and efficient calculation of the self-energy, which has a complicated
      pole structure for core states. The accuracy of our method is validated by
      comparing to a fully analytic GW algorithm. Furthermore, we report the obtained
      core-level binding energies and their deviations from experiment for a set of
      small molecules and large polycyclic hydrocarbons. The core-level excitations
      computed with our GW approach deviate by less than 0.5 eV from the experimental
      reference. For comparison, we also report core-level binding energies calculated
      by density functional theory (DFT)-based approaches such as the popular delta
      self-consistent field (DeltaSCF) method. Our implementation is optimized for
      massively parallel execution, enabling the computation of systems up to 100
      atoms.

PMID- 30092141
TI  - Telemedicine Coverage of Intensive Care Units: A Narrative Review.
AB  - Telemedicine coverage of intensive care units (ICUs) is an organizational
      innovation that has been touted as a means to improve access to and quality of
      critical care. The purpose of this narrative review is to discuss the different
      organizational models of ICU telemedicine and factors that have influenced its
      adoption, and to review the existing literature to consider whether it has lived
      up to its promise. We conclude by suggesting future directions to fill in some of
      the existing gaps in the evidence.

PMID- 30092142
TI  - Bicelle composition-dependent modulation of phospholipid dynamics by apelin
      peptides.
AB  - Apelin peptides are cognate ligands for the apelin receptor, a G-protein-coupled
      receptor (GPCR). The apelinergic system plays critical roles in wide-ranging
      physiological activities including function and development of the central
      nervous and cardiovascular systems. Apelin is found in 13-55 residue isoforms in
      vivo, all of which share the C-terminal portion of the preproapelin precursor.
      Characterization of high-resolution structures and detergent micelle interactions
      of apelin-17 led to a two-step membrane-catalyzed binding and GPCR activation
      mechanism hypothesis recapitulated in longer isoforms. Here, we examine
      interactions of the apelin-13 and -17 isoforms with isotropic zwitterionic and
      mixed zwitterionic-anionic lipid bicelles to test for hallmarks of membrane
      catalysis in a more physiological membrane-mimetic environment than a micelle.
      Specifically, 1H and 31P relaxation and diffusion solution-state NMR techniques
      demonstrate that both apelin isoforms interact with both types of isotropic
      bicelles. Bicelle hydrodynamics were observed to be differentially modulated by
      apelin peptides, although these effects were minimal. Phospholipid headgroup 31P
      spin relaxation behaviour was, conversely, clearly perturbed. Perturbation of
      this nature was also observed in magnetically aligned bicelles by 31P solid-state
      NMR spectroscopy and spin relaxation experiments. This behaviour is consistent
      with an apelin-bicelle binding process allowing significant peptide mobility,
      facilitating membrane-catalyzed GPCR encounter.

PMID- 30092143
TI  - Dose Optimization of H56:IC31 Vaccine for TB Endemic Populations: A Double-Blind,
      Placebo-Controlled, Dose-Selection Trial.
AB  - BACKGROUND: Global tuberculosis (TB) control requires effective vaccines in TB
      endemic countries, where most adults are infected with Mycobacterium tuberculosis
      (M.tb). We aimed to define optimal dose and schedule of H56:IC31, an experimental
      TB vaccine comprising Ag85B, ESAT-6, and Rv2660c, for M.tb-infected and
      uninfected adults. METHODS: We enrolled 98 healthy, HIV-uninfected, BCG
      vaccinated, South African adults. M.tb infection was defined by QuantiFERON (QFT)
      assay. QFT-negative participants received two vaccinations of different
      concentrations of H56 in 500nmol of IC31(r) to enable dose selection for further
      vaccine development. Subsequently, QFT-positive and negative participants were
      randomized to receive two or three vaccinations to compare potential schedules.
      Participants were followed for safety and immunogenicity for 292 days. RESULTS:
      H56:IC31 showed acceptable reactogenicity profiles irrespective of dose, number
      of vaccinations, or M.tb infection. No vaccine-related severe or serious adverse
      events were observed. The three H56 concentrations tested induced equivalent
      frequencies and functional profiles of antigen-specific CD4 T cells. ESAT-6 was
      only immunogenic in QFT-negative participants who received three vaccinations.
      CONCLUSIONS: Two or three H56:IC31 vaccinations at the lowest dose induced
      durable antigen-specific CD4 T cell responses with acceptable safety and
      tolerability profiles in M.tb-infected and uninfected adults. Additional studies
      should validate applicability of vaccine doses and regimens to both QFT-positive
      and negative individuals. Clinical trial registration available at
      www.clinicaltrials.gov, ID NCT01865487.

PMID- 30092144
TI  - Mycobacterium avium Complex and Bronchiectasis. There's Something Happening Here
      . . .

PMID- 30092145
TI  - WNT5a in Extracellular Vesicles - A New Frontier for Pulmonary Fibrosis.

PMID- 30092146
TI  - What We Talk about When We Talk about Exacerbations of COPD.

PMID- 30092147
TI  - Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia on Somatostatin
      Receptor Imaging.

PMID- 30092148
TI  - Primary Pulmonary Artery Lipoma Mimicking Pulmonary Thromboembolism.

PMID- 30092150
TI  - Bluff, E. (2015). Safe design and construction of machinery: regulation, practice
      and performance. Farnham: Ashgate.

PMID- 30092149
TI  - Combination therapies for hypertension - why we need to look beyond RAS blockers.
AB  - INTRODUCTION: Hypertension is the leading cause of mortality and disability
      worldwide. Despite the proven benefits of blood pressure (BP) reduction, lack of
      BP pressure control continues to be the most important clinical problem in
      hypertension management. Areas covered: Factors involved in the lack of BP
      control and strategies to improve such control have been reviewed, with special
      focus on the usefulness of combination therapies, those types of combination
      which include a renin-angiotensin system (RAS) blocker, with diuretics, calcium
      channel blockers, or both. Expert commentary: Combination therapy is required for
      BP control in most hypertensive patients. RAS blockers should be included in such
      combinations, except contraindicated. Diuretics, and especially calcium channel
      blockers are the drugs of choice for double or triple combinations. Diuretics
      stimulate RAS and enhance the effect of RAS blockers, while minimizing the
      undesirable metabolic effects of diuretics. RAS blockers and calcium channel
      blockers have synergistic protective effects on the vascular wall and have
      demonstrated to be superior to other types of combinations, thus becoming the
      preferred initial treatment for most hypertensive patients. The use of single
      pill combinations is associated with better treatment adherence, thus
      facilitating the achievement of adequate BP control.

PMID- 30092152
TI  - Early trajectory features and the course of psychotherapy.
AB  - OBJECTIVE: We investigated the relationship between psychotherapy outcome and
      trajectory variables measured during the first five treatment sessions. METHOD:
      In a psychotherapy training clinic, 158 patients completed a measure of
      symptomatic distress at each visit during treatment lasting a median 30 sessions.
      We investigated outcome predictions based on symptomatic distress at intake,
      change in distress between the first and fifth sessions, and intersession shifts.
      RESULTS: Elevated symptomatic distress at intake predicted reliable change, while
      limited initial distress predicted clinically significant improvement; both
      predictions were independent of those by other trajectory variables. Large early
      change and large intersession shifts yielded similar predictions of reliable
      change and clinically significant improvement. Greater change between the first
      and fifth sessions predicted less change in subsequent sessions. By contrast,
      neither initial distress nor early intersession shifts predicted change in
      distress after the fifth session. CONCLUSION: Considered together, symptomatic
      distress at intake and change in distress over the first five sessions improve
      the prediction of psychotherapy outcome over base rate. Intersession shifts
      contribute little to the prediction of outcome after accounting for overall
      change in symptomatic distress during the first five sessions.

PMID- 30092153
TI  - Managing recurrent urinary tract infections in kidney transplant patients.
AB  - INTRODUCTION: Recurrent urinary tract infections (UTI) are a common clinical
      problem in kidney transplant recipients. Due to the complex urological anatomy
      derived from the implantation of the kidney graft, the spectrum of the disease
      and the broad underlying pathophysiological mechanisms. Recurrent UTI worsen the
      quality of life, decrease the graft survival and increase the costs of kidney
      transplantation. Areas covered: In this review, we describe the definitions,
      clinical characteristics, pathophysiological mechanisms and microbiology of
      recurrent urinary tract infections in kidney transplantations. The actual
      published literature on the management of recurrent urinary tract infections is
      based on case series, observational cohorts and very few clinical trials. In this
      review, the available evidence is compiled to propose evidence-based strategies
      to manage these complex cases. Expert commentary: The management of recurrent
      urinary tract infections in kidney transplant patients requires a proper
      diagnosis of the underlying mechanism. Early identification of structural or
      functional urological abnormalities, potentially amenable for surgical
      correction, is crucial for a successful management. The use of antibiotics to
      prevent recurrent infections should be carefully evaluated to avoid side effects
      and emergence of antibiotic-resistant microorganisms.

PMID- 30092151
TI  - Guidance toward the implementation of multicriteria decision analysis framework
      in developing countries.
AB  - INTRODUCTION: Multiple Criteria Decision Analysis (MCDA) is increasingly used in
      health care mainly because it moves decision-making from ad hoc to an evidence
      based and comprehensive process. Developing countries with more restricted
      financial and human research capacities, however, should consider their own
      methods of MCDA development and implementation. Areas covered: An MCDA framework
      to improve procurement decisions of off-patent pharmaceuticals was developed for
      developing countries and adapted to Indonesia, Kazakhstan and Vietnam during
      three policy workshops. Based on the experience of these workshops and one joint
      workshop with international experts and decision makers from multiple developing
      countries, general recommendations were formulated on how to implement MCDA
      specifically in developing countries. We provide 17 practical MCDA implementation
      recommendations in four major areas, including (1) MCDA objectives; (2) technical
      considerations of MCDA tool; (3) development and customization of MCDA tool and
      (4) policy implementation of MCDA in decision-making. Expert commentary: These
      practical MCDA recommendations for developing countries contribute to feasible,
      transparent, stepwise, iterative and standardized decision-making in health care.

PMID- 30092154
TI  - The use of the Cochlear Mini Microphone (MM) as a personal radio system (FM) with
      young children who are deaf.
AB  - OBJECTIVES: This paper describes the background, organization and findings of a
      project undertaken in 2016-2017, to examine the benefits and challenges of the
      use of the Cochlear Mini Microphone (MM) by the families of pre-school children
      with cochlear implants on the Nottingham Auditory Implant Programme. METHODS: The
      experiences and views of 25 families who used the equipment were obtained and
      analysed. The information informed subsequent advice, patient literature and
      professional training. RESULTS: The MM was viewed to be of benefit by just under
      half of the families. The attitudes and technical competence of families and
      local professionals, alongside the age and lifestyle of the children, were
      identified as the key factors affecting the amount of use. CONCLUSION: The
      insights gained into the challenges and benefits of the MM for this population
      offered explanations for the limited take-up of the equipment and informed ways
      to encourage appropriate use Discussion: Equipment issued to very young children
      works best alongside specific advice and training, targeted at both families and
      local professionals. Despite some technical limitations, the availability of a
      personal radio system was found to be of benefit by some families. It encouraged
      consideration by both families and professionals, of the potential benefits of
      early introduction of a personal radio system into pre-school group activities
      and educational settings.

PMID- 30092156
TI  - Reactivation of human herpesviruses 6 and 7 in Kawasaki disease.
AB  - OBJECTIVES: Kawasaki disease (KD) is one of the most common childhood
      vasculitides. Some serological studies have suggested an etiological relationship
      between KD and human herpesvirus (HHV)-6 or HHV-7. However, primary or
      reactivated HHV-6 and -7 has not been fully investigated in patients with KD.
      METHODS: Twenty-three patients with KD were prospectively enrolled in this study.
      Peripheral blood was collected in the acute and convalescence phases, and HHV-6
      and -7 viral loads were measured by real-time PCR. RESULTS: In the acute phase,
      HHV-6 and -7 DNA was detected in 7 (30%) patients each, compared to 13 (57%) and
      9 (39%) patients in the convalescence phase, respectively. HHV-6 and -7 DNA loads
      were significantly higher in the convalescence phase than in the acute phase.
      Significant increases in HHV-6 and -7 DNA loads were not observed in disease
      control patients. Taking into account HHV-6 and -7 serostatus, reactivation of
      HHV-6 and -7 was observed in 7 and 9 patients, respectively. KD patients with HHV
      6 reactivation showed higher C-reactive protein levels and more frequently
      required steroid therapies than patients without reactivation. CONCLUSION: HHV-6
      and -7 reactivation is frequent in KD patients. HHV-6 reactivation might
      exacerbate the severity of KD.

PMID- 30092155
TI  - 'If I had not taken it [HIVST kit] home, my husband would not have come to the
      facility to test for HIV': HIV self-testing perceptions, delivery strategies, and
      post-test experiences among pregnant women and their male partners in Central
      Uganda.
AB  - BACKGROUND: HIV self-testing (HIVST) can improve HIV-testing rates in 'hard-to
      reach' populations, including men. We explored HIVST perceptions, delivery
      strategies, and post-test experiences among pregnant women and their male
      partners in Central Uganda. METHODS: This was a qualitative study implemented as
      part of a pilot, cluster-randomized oral HIVST intervention trial among 1,514
      pregnant women attending antenatal care services at three health facilities in
      Central Uganda. The qualitative component of the study was conducted between
      February and March 2017. We conducted 32 in-depth interviews to document women
      and men's perceptions about HIVST, strategies used by women in delivering the
      kits to their male partners, male partners' reactions to receiving kits from
      their female partners, and positive and negative social outcomes post-test. All
      interviews were audio-recorded, transcribed verbatim, and analyzed manually
      following a thematic framework approach. RESULTS: Women were initially anxious
      about their male partners' reaction if they brought HIVST kits home, but the
      majority eventually managed to deliver the kits to them successfully. Women who
      had some level of apprehension used a variety of strategies to deliver the kits
      including placing the kits in locations that would arouse male partners'
      inquisitiveness or waited for 'opportune' moments when their husbands were likely
      to be more receptive. A few (three) women lied about the purpose of the test kit
      (testing for syphilis and other illnesses) while one woman stealthily took a
      mucosal swab from the husband. Most men initially doubted the ability of oral
      HIVST kits to test for HIV, but this did not stop them from using them. Both men
      and women perceived HIVST as an opportunity to learn about each other's HIV
      status. No serious adverse events were reported post-test. CONCLUSION: Our
      findings lend further credence to previous findings regarding the feasibility of
      female-delivered HIVST to improve male partner HIV testing in sub-Saharan Africa.
      However, support for women in challenging relationships is required to minimize
      potential for deception and coercion.

PMID- 30092157
TI  - Three-monthly bolus vitamin D supplements (1000 vs 400 IU/day) for prevention of
      bone loss in children with difficult-to-treat nephrotic syndrome: a randomised
      clinical trial.
AB  - BACKGROUND: Nephrotic syndrome (NS) in children is one of the most common chronic
      diseases with a remitting and relapsing course. Glucocorticoids (prednisolone)
      are considered to be the treatment of choice but are associated with
      osteoporosis. There are no uniform consensus guidelines regarding the optimum
      dose of calcium and vitamin D for osteoprotection. Some authorities suggest a
      daily dose of 1000 IU vitamin D for children for osteoprotection, while others
      suggest a daily dose of 400 IU. OBJECTIVES: To compare the efficacy of three
      monthly bolus vitamin D supplementation (1000 vs 400 IU/day) to prevent bone loss
      in children with difficult-to-treat NS (DTNS). METHODS: In this parallel-group,
      open-label, randomised clinical trial, 60 children aged 1-18 years with DTNS [37
      with frequently relapsing NS (FRNS), 13 steroid-dependent NS (SDNS) and 10
      steroid-resistant NS (SRNS)] were enrolled and block randomised in a 1:1
      allocation ratio to receive 1000 IU/day vitamin D (Group A, n = 30) or 400 IU/day
      (Group B, n = 30), administered as three-monthly bolus supplemental doses. In
      Group A, vitamin D (cholecalciferol, Calcirol(r)sachet) was administered as a
      stat dose of 90,000 IU every three months (calculated for a period of three
      months at 1000 IU/day). In Group B, vitamin D (cholecalciferol) was administered
      as a stat dose of 36,000 IU every three months (calculated for a period of three
      months at 400 IU/day). The proportionate change in bone mineral content (BMC) was
      studied by dual energy X-ray absorptiometry (DEXA) scan in both groups after
      vitamin D supplementation by analysing the values of BMC obtained 12 months apart
      (baseline vs. after 12 months). RESULTS: Sixty children were randomised to
      receive vitamin D at a dose of either 1000 IU/day (Group A) or 400 IU/day (Group
      B). The two groups were comparable in their baseline clinical and laboratory
      parameters (including BMC and bone mineral density (BMD)). The distribution of
      the three types of NS (FRNS, SDNS and SRNS) was also comparable in both groups.
      In Group A, there were 19, 6 and 5 children with FRNS, SDNS and SRNS,
      respectively, and in Group B there were 18, 7 and 5 children with FRNS, SDNS and
      SRNS, respectively. The proportionate change in BMC was not significantly
      different between the two groups (median proportionate change in BMC in Group A
      13.36% vs 11.59% in Group B, p = 0.22). Overall, BMC increased in both groups
      (96.7% in each). Only one (3.3%) patient in each group exhibited bone loss. None
      of the patients had a urinary calcium:creatinine ratio >0.2 at the end of the
      study. CONCLUSION: Three-monthly bolus vitamin D dosing regimens administered
      either as 1000 or 400 IU/day prevent bone loss in children with DTNS who require
      long-term steroids. Overall, three-monthly bolus supplemental prophylactic
      vitamin D, either 1000 or 400 IU/day, would seem to be an effective strategy for
      preventing bone loss in children with DTNS, as evidenced by the extremely low
      rates of bone loss (3.3% in each group), and is useful for delivering optimal
      care to children with DTNS. However, since this study was designed as an
      equivalence trial and not a superiority trial, further studies are required to
      demonstrate the superiority of the former regimen over the latter. ABBREVIATIONS:
      BMC, bone mineral content; BMD, bone mineral density; DEXA, dual energy X-ray
      absorptiometry; DTNS, difficult-to-treat nephrotic syndrome; FRNS, frequently
      relapsing nephrotic syndrome; IFRNS, infrequently relapsing nephrotic syndrome;
      iPTH, intact parathyroid hormone; NS, nephrotic syndrome; SDNS, steroid-dependent
      nephrotic syndrome; SRNS steroid-resistant nephrotic syndrome.

PMID- 30092159
TI  - When team member familiarity affects transactive memory and skills: a simulation
      based training among police teams.
AB  - The goal of this study was to evaluate the impact of team member familiarity on
      both technical and non-technical skills of police officers and to examine the
      mediating role of transactive memory components (specialization, coordination and
      credibility). Student police officers (N = 150) carried out professional
      simulation sessions in groups of three, with either familiar (n = 22 teams) or
      unfamiliar (n = 28 teams) team members, followed by a skills evaluation exercise.
      Professional instructors evaluated skills through direct observation of team
      member behaviours. The results revealed that training in familiar teams improved
      police officers' technical and non-technical skills and transactive memory
      system. The effect of team familiarity on skills was mediated by transactive
      memory and specifically by the tacit coordination component. The findings are
      discussed in relation to the literature on the effects of team member familiarity
      on team performance, and implications for team training and staffing (turnover of
      personnel) in actions teams. Practitioner Summary: This study examined the effect
      of team member familiarity on both the technical and non-technical skills of
      police officers. Training in familiar teams improved skills and transactive
      memory. The positive effect of team member familiarity on skills was mediated by
      the coordination facet of transactive memory.

PMID- 30092158
TI  - Ten-years trend of dengue research in Indonesia and South-east Asian countries: a
      bibliometric analysis.
AB  - BACKGROUND: Dengue fever is a mosquito-borne viral disease with high incidence in
      over 128 countries. WHO estimates 500,000 people with severe dengue are
      hospitalized annually and 2.5% of those affected die. Indonesia is a hyperendemic
      country for dengue with an increasing number of cases in the last decade.
      Unfortunately, the trends of Indonesian dengue research are relatively unknown.
      OBJECTIVE: This research aimed to depict bibliographic trends and knowledge
      structure of dengue publications in Indonesia relative to that of South-east Asia
      (SEA) from 2007 to 2016. METHODS: Bibliographic data were collected from PubMed
      filtered by Indonesia country affiliation. The annual growth rate of publication
      was measured and compared with neighborhood countries in the SEA region. Network
      analysis was used to visualize emerging research issues. RESULTS: About 1,625
      dengue-related documents originated from SEA region, of which Indonesia
      contributed 5.90%. The publication growth rate in Indonesia, however, is the
      highest in ASEAN region (28.87%). Total citations for documents published from
      Indonesia was 980, with an average of 14 citations per publication and h-index of
      16. Within the first five years, the main research topics were related to insect
      vector and diagnostic method. While insect vector remained dominant in the last
      five years, other topics such as disease outbreak, dengue virus, and dengue
      vaccine started emerging. CONCLUSION: In the last 10 years, dengue publications'
      growth from Indonesia in international journals improved significantly, despite
      less number of publications compared to other SEA countries. Efforts should be
      made to improve the quantity and quality of publications from Indonesia. The
      research topics related to dengue in Indonesia are in line with studies in SEA.
      Stakeholders and policy makers are encouraged to develop a roadmap for dengue
      research in the future.

PMID- 30092160
TI  - The controversies surrounding polypharmacy in old age - where are we?

PMID- 30092161
TI  - Three-year safety and two-year effectiveness of etanercept in patients with
      rheumatoid arthritis in Japan: Results of long-term postmarketing surveillance.
AB  - OBJECTIVES: To evaluate the real-world safety and effectiveness of etanercept
      (ETN) in Japanese patients with rheumatoid arthritis. METHODS: This postmarketing
      surveillance study (NCT00503139) assessed the safety and effectiveness of ETN
      treatment over 3 and 2 years (from June 2007 to September 2011), respectively.
      Safety was evaluated by occurrence and seriousness of adverse drug reactions
      (ADRs), and of adverse events (AEs) for malignancies. Effectiveness was assessed
      using the Disease Activity Score in 28 joints based on the erythrocyte
      sedimentation rate (ESR) with four variables (swollen and tender joint counts,
      ESR, and patient global assessment; DAS28-4/ESR). Treatment was considered
      effective if patients had a good/moderate response by the European League Against
      Rheumatism response criteria. RESULTS: ADRs occurred in 256/675 (37.9%) patients,
      the most common being injection site reactions (4.4%) and nasopharyngitis (3.3%).
      Serious ADRs occurred in 60/675 (8.9%) patients, the most frequent being
      pneumonia (1.2%). The incident rate of malignancies (AEs) was 1.06 per 100
      patient-years. Mean baseline DAS28-4/ESR for the 581 patients included in
      effectiveness analysis was 5.42, which decreased to 3.32 at 2 years. Eighty-two
      percent of patients achieved a moderate/good response at 2 years. CONCLUSION:
      Long-term ETN treatment safety and effectiveness were sustained over 3 and 2
      years, respectively.

PMID- 30092162
TI  - Neuropsychology: from theory to practice (2nd edition).

PMID- 30092163
TI  - Prevalence and factors associated with sarcopenia in patients with rheumatoid
      arthritis.
AB  - OBJECTIVES: Sarcopenia is characterized by loss of muscle strength and mass,
      leading to falls and adverse health outcomes. Our aim was to determine the
      prevalence of sarcopenia in patients with rheumatoid arthritis (RA) and to
      identify factors associated with sarcopenia in these patients. METHODS: A cross
      sectional study of 388 consecutive women with RA was conducted, assessing muscle
      mass and strength, and walking speed. Falls and bone fractures sustained over the
      prior year were evaluated. The association between sarcopenia and RA
      characteristics, falls, and bone fractures was evaluated using logistic
      regression analyses. RESULTS: The prevalence of sarcopenia was 37.1% (14.7%,
      severe sarcopenia; 22.4%, sarcopenia), with 49.0% classified as having low muscle
      mass. The incidence of falls, fractures, and lower bone mineral density was
      higher in patients with than without sarcopenia. Age, RA duration, Steinbrocker's
      stage, the high Mini-Nutritional Assessment-Short Form score and the use of
      biological disease-modifying anti-rheumatic drugs (bDMARDs) were independent
      factors associated with sarcopenia. CONCLUSION: We confirmed that sarcopenia
      develops in a significant proportion of patients with RA. Age, longer disease
      duration, joint destruction and malnutrition were positively associated with
      sarcopenia, with the use of bDMARDs being negatively associated.

PMID- 30092164
TI  - Controlled-release pregabalin in the treatment of fibromyalgia.
AB  - INTRODUCTION: Fibromyalgia (FM) is a chronic disorder whose symptoms of musculo
      skeletal pain, fatigue, sleep disturbances, and cognitive impairment pervade the
      personal, occupational, and social aspects of a patient's life. Together with the
      antidepressants duloxetine and milnacipran, the anticonvulsant pregabalin (PGB)
      is one of the three drugs approved by the Food and Drug Administration for the
      treatment of FM. The aim of this narrative review is to summarize the data
      relating to the efficacy and safety of the controlled-release formulation of PGB
      (PGB-CR) in patients with FM. Areas covered: Efforts by the pharmaceutical
      industry have led to the introduction of new formulations of already approved
      drugs to enhance treatment convenience and adherence. Expert opinion: Although
      there are no published studies specifically comparing PGB-CR and PGB-IR
      formulations in FM patients, the efficacy and safety profiles of PGB-CR seem to
      be similar to those of the IR formulation, and the convenience of once-daily
      dosing potentially enhances patient compliance. However, the amount of evidence
      is not sufficient to draw any definite conclusions, and further studies of larger
      patient samples are needed.

PMID- 30092165
TI  - Novel alternatives to extracellular vesicle-based immunotherapy - exosome
      mimetics derived from natural killer cells.
AB  - Exosomes are endogenous nanocarriers that can deliver biological information
      between cells. They are secreted by all cell types, including immune cells such
      as natural killer (NK) cells. However, mammalian cells release low quantities of
      exosomes, and the purification of exosomes is difficult. Here, nanovesicles were
      developed by extrusion of NK cells through filters with progressively smaller
      pore sizes to obtain exosome mimetics (NK-EM). The anti-tumour effect of the NK
      EM was confirmed in vitro and in vivo. The morphological features of the NK-EM
      were revealed by transmission electron microscopy (TEM), nanoparticle tracking
      analysis (NTA) and Western blot. In vitro, the cytotoxicity of the NK-EM to
      cancer cells (glioblastoma, breast carcinoma, anaplastic thyroid cancer and
      hepatic carcinoma) was assessed using bioluminescence imaging (BLI) and CCK-8
      assay. For in vivo study, a xenograft glioblastoma mouse model was established.
      The anti-tumour activity of NK-EM was confirmed in vivo by the significant
      decreases of BLI, size and weight (all p < .001) of the tumour compared with the
      control group. Moreover, NK-EM cytotoxicity for glioblastoma cells that related
      with decreased levels of the cell survival markers p-ERK and p-AKT, and increased
      levels of apoptosis protein markers cleaved-caspase 3, cytochrome-c and cleaved
      PARP was confirmed. All those results suggest that NK-EM exert stronger killing
      effects to cancer cells compared with the traditional NK-Exo, at the same time,
      the tumour targeting ability of the NK-EM was obtained in vivo. Therefore, NK-EM
      might be a promising immunotherapeutic agent for treatment of cancer.

PMID- 30092166
TI  - Typhlitis as a complication of influenza in a patient with advanced HIV
      infection.
AB  - The authors report the case of an HIV-infected patient who presented with
      typhlitis as a complication of typical influenza. To the best of their knowledge,
      this is the first case reported in the literature with such an association of
      clinical conditions.

PMID- 30092167
TI  - Vitamin E administration erases an enhanced oxidation in multiple sclerosis.
AB  - Systemic peroxidation status has been reported as a pathogenic factor for
      multiple sclerosis (MS). Systemically elevated oxidation levels are associated
      with serum lipid peroxidation and somatic telomere length (TL) shortening. We
      investigated whether vitamin E (VE) administration suppresses peroxidation and
      improves clinical symptoms in 34 MS patients. We analyzed serum lipid
      peroxidation and degree of TL in circulating leukocytes of MS patients before and
      after VE treatment. The oxidation level was enhanced and TL was shortened in MS.
      The MS population treated with VE 400 mg/day for 3 months showed significantly
      reduced serum lipid oxidation level with maintenance of TL. These findings showed
      that systemic peroxidation is associated with the development of MS. Antioxidants
      such as vitamin E can be candidates for supplementary therapeutic agents for MS.

PMID- 30092168
TI  - Arginine-lowering enzymes against cancer: a technocommercial analysis through
      patent landscape.
AB  - INTRODUCTION: Rise in incidence of various cancers and growing adoption of
      biological therapy to avoid side effects of conventional cancer therapies is
      driving the growth of the cancer biotherapy market globally. One such therapy
      available for the treatment of certain tumors employs arginine-lowering enzymes
      (ALEs). Several patents have been filed in this technology domain, and many Phase
      I/II clinical trials of the ALEs especially arginine deiminase (ADI) are
      underway. Areas covered: Patents and clinical trials in the domain of ALEs for
      the treatment of cancer were studied with an objective to understand technology
      trends, targeted areas, key players, and inventors involved. Expert opinion:
      Amongst the various ALEs, ADI is the most promising enzyme for cancer therapy.
      ADI-based cancer therapy holds potential in treating liver, skin, lung,
      gastrointestinal, and blood cancer. ADI-PEG20 has proved to be very effective
      when used as a component of combination therapy in a first-line treatment.
      Polaris Group holds the worldwide rights for ADI-PEG20 and is the leading player
      in developing ADI as a therapeutic agent. Many clinical studies, especially in a
      combinatorial approach, are underway whose success will pave the way for ADI-PEG
      to the multimillion cancer market.

PMID- 30092169
TI  - Should endometriosis be managed within a chronic disease framework? An analysis
      of national policy documents.
AB  - Objective The aim of this study was to determine whether endometriosis meets the
      definition for chronic disease in Australian policy documents.Methods A
      qualitative case study approach was used to thematically analyse the definitions
      contained in Australian chronic disease policy documents and technical reports.
      The key themes were then compared with descriptions of endometriosis in peer
      reviewed literature, clinical practice guidelines and expert consensus
      statements.Results The search yielded 18 chronic disease documents that provided
      a definition or characteristics of chronic disease. The thematic analysis
      identified key elements of chronic diseases pertaining to onset, causation,
      duration, treatment, disease course and impact (individual and societal). A
      comparison with endometriosis descriptions indicated that endometriosis meets
      five of the six chronic disease key elements.Conclusion In Australia, long-term
      and complex conditions are managed within a chronic disease framework and include
      mechanisms such as chronic disease management plans (CDMPs) to assist with
      coordination and management of these conditions. Because endometriosis has most
      of the characteristics of chronic disease, it could potentially be reframed as a
      chronic disease in endometriosis clinical practice guidelines and consensus
      statements. Further, the use of CDMPs may provide a mechanism to promote
      individualised care and multidisciplinary management of this chronic, enigmatic
      and debilitating disease.What is known about the topic? In Australia, long-term
      complex diseases can be managed within a chronic disease framework that include
      mechanisms for coordinated care such as CDMPs and team care arrangements.
      Endometriosis is described as an inflammatory, progressive, relapsing and, for
      some women, debilitating condition, but is rarely described as a chronic disease
      in the clinical practice guidelines and consensus statements available in
      Australia.What does this paper add? Endometriosis shares most of the
      characteristics of a chronic disease so may benefit from chronic disease
      management systems such as CDMPs.What are the implications for practitioners?
      CDMPs may be a useful mechanism to coordinate and improve the effectiveness of
      care for women with endometriosis who experience sustained symptoms of
      endometriosis.

PMID- 30092170
TI  - Identification of essential hypertension biomarkers in human urine by non
      targeted metabolomics based on UPLC-Q-TOF/MS.
AB  - BACKGROUND: In recent years, using metabolomics technology to study hypertension
      has made some progress. However, in actual clinical studies, there are few
      studies on hypertension related metabonomics with human urine as samples. In this
      study, the urine samples of patients with essential hypertension (EH) were
      studied by comparing with healthy people to explore the changes of urine
      metabolites between hypertensive patients and healthy people in order to find
      potential biomarkers and metabolic pathways. METHODS: An ultra performance liquid
      chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q
      TOF/MS) technology was used to analyze the urine metabolites of 75 cases of
      essential hypertension group (EH) and 75 cases of healthy control group (HC).
      RESULTS: According to the PLS-DA pattern recognition analysis, substances with
      significant differences (P < .05) between the EH group and the HC group were
      screened out, including 10 potential biomarkers such as L-methionine. The
      metabolic pathways involved were amino acid metabolism, fatty acid metabolism
      steroid hormone, biosynthesis and oxidative stress. CONCLUSION: The non-targeted
      metabolomics based on UPLC-Q-TOF/MS technology can effectively identify the
      differential metabolites of potential biomarkers in the urine of essential
      hypertensive patients and provide a theoretical basis for the treatment of
      clinical hypertension.

PMID- 30092171
TI  - Virus infection reduces shoot proliferation of in vitro stock cultures and
      ability of cryopreserved shoot tips to regenerate into normal shoots in 'Gala'
      apple (Malus * domestica).
AB  - Plant cryopreservation has provide secure back-ups of germplasm collections of
      vegetatively propagated crops. Often, recovery levels vary among laboratories
      when the same cryogenic procedures are used for the same genotypes. The present
      study investigated the effects of Apple stem grooving virus (ASGV) on shoot
      proliferation of in vitro stock cultures and recovery of cryopreserved shoot tips
      of 'Gala' apple. Results showed that virus infection reduced shoot proliferation
      of in vitro stock cultures and cell ability to regenerate normal shoots in
      cryopreserved shoot tips. Virus infection increased total soluble protein, total
      soluble sugar and free proline levels and altered endogenous levels of
      indoleacetic acid (IAA) and zeatin riboside (ZR), but induced severe cell
      membrane damage and caused alternation in mitochondria shape of the in vitro
      stock shoots. The altered levels of IAA and ZR were most likely to be responsible
      for the reduced shoot proliferation of in vitro stock culture. Cell damage and
      alternations in mitochondria shape in ASGV-infected shoot tips were most likely
      responsible for the reduced cell ability to regenerate normal shoots following
      cryopreservation. To the best of our knowledge, this is the first study on
      effects of virus infection on recovery of cryopreserved shoot tips. Results
      reported here emphasize that healthy in vitro stock cultures should be used for
      cryopreservation.

PMID- 30092172
TI  - Treatment with chemical delipidation forskolin prior to cryopreservation improves
      the survival rates of swamp buffalo (Bubalus bubalis) and bovine (Bos indicus) in
      vitro produced embryos.
AB  - The cryopreservation of embryos is a technology developed for long-term genetic
      preservation. However, high sensitivity to low temperatures due to a large number
      of intracellular lipids within ruminant embryos compromises the success of this
      technique. The aim of this study was to examine the effects of using of lipolytic
      chemical agent forskolin, during in vitro producing of buffalo and bovine embryos
      on lipid contents, cryotolerance and subsequent developmental competence of these
      embryos. Buffalo and bovine oocytes were collected by the aspiration technique
      from follicles and submitted for in vitro fertilisation; the embryos were later
      divided into four experiments. Experiment 1, buffalo and bovine embryos were pre
      treated in the presence and absence of 10 MUM forskolin for 24 h. Lipid contents
      were determined by Nile red staining and confocal microscopy. We found that 10
      MUM forskolin was capable to reduce lipid contents within developing embryos in
      both of species (P < 0.01). Lipid contents within Day 2 embryos exhibited greater
      fluorescence intensity than did Day 7 embryos in both animal species. The purpose
      of Experiment 2 was to investigate the adverse effects of 10 MUM forskolin on
      embryo development. In Experiments 3 and 4, Day 2 (4- to 8-cell stage) and Day 7
      (blastocyst stage) embryos were pre-treated with 10 MUM forskolin for 24 h and
      further cryopreserved with a controlled-rate freezing technique. The successful
      cryopreservation was determined by post-thawed embryonic development in vitro.
      The results showed that the blastocyst rate of the 4-8 cell stage in the
      forskolin-treated group had increased in both species, while the hatching and
      hatched blastocyst rates of forskolin-treated day 7 bovine embryos were
      significantly higher than those of the non-treated group (52.1% vs. 39.4%; P <
      0.05). However, delipidation with forskolin did not affect the developmental rate
      of the day 7 buffalo embryos (P = 0.73). Our studies showed that delipidation by
      forskolin treatment increased the survival rate of cryopreservation in buffalo
      and bovine in vitro produced embryos.

PMID- 30092173
TI  - Towards a more holistic view of fertility: The need to consider biological
      underpinnings rather than only data.

PMID- 30092174
TI  - Timing is crucial: Some critical thoughts on using LH tests to determine women's
      current fertility.
AB  - Naturally cycling women reportedly go through a variety of psychological and
      behavioural changes over menstrual cycle. Evolutionary informed scholars have
      interpreted such changes as maximising reproductive success. However, concerns
      have been raised regarding this ovulatory shift hypothesis, since recent studies
      have yielded inconsistent findings. We suggest that the inconsistent findings
      regarding the ovulatory shift hypothesis may result from a too simplistic
      definition of the fertile window. Presently, most studies use LH tests to
      determine the fertile window. The problem with this "gold standard" is that it
      builds on the misconception that fertility peaks with ovulation and that
      ovulation regularly occurs 24 to 48 hours after the LH surge. While commercially
      available urinary LH test strips are a cheap and easy way to reliably detect LH
      surges, the LH surge itself marks the impending end of the fertile window. So if
      women are invited to the laboratory after the LH surge (as is often done for
      practical reasons) there is a high probability of misclassifying women as fertile
      when in fact the fertile window has already closed. We discuss possible
      advancements that may help to increase the accuracy and reliability of
      determining a woman's individual fertile window, during which any adaptive
      changes that increase the chance of reproduction should be best observable.

PMID- 30092175
TI  - Immune Cell and Stromal Signature Associated With Progression-Free Survival of
      Patients With Resected Pancreatic Ductal Adenocarcinoma.
AB  - BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal
      adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We
      studied the associations between composition of the pancreatic stroma
      (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by
      inflammatory cells and times of progression-free survival (PFS) of patients with
      PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from
      385 patients included in the European Study Group for Pancreatic Cancer trial 1
      and 3 and performed immunohistochemistry to detect alpha smooth muscle actin,
      type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils. Tumors that
      expressed high and low levels of these markers were compared with patient
      outcomes using Kaplan-Meier curves and multivariable recursive partitioning for
      discrete-time survival tree analysis. Prognostic index was delineated by a
      multivariable Cox proportional hazards model of immune cell and stromal markers
      and PFS. Findings were validated using 279 tissue microarray specimens from 93
      patients in a separate cohort. RESULTS: Levels of CD3, CD4, CD8, CD68, and CD206
      were independently associated with tumor recurrence. Recursive partitioning for
      discrete-time survival tree analysis identified a high level of CD3 as the
      strongest independent predictor for longer PFS. Tumors with levels of CD3 and
      high levels of CD206 associated with a median PFS time of 16.6 months and a
      median prognostic index of -0.32 (95% confidence interval [CI] -0.35 to -0.31),
      whereas tumors with low level of CD3 cell and low level of CD8 and high level of
      CD68 associated with a median PFS time of 7.9 months and a prognostic index of
      0.32 (95% CI 0.050-0.32); we called these patterns histologic signatures. Stroma
      composition, when unassociated with inflammatory cell markers, did not associate
      significantly with PFS. In the validation cohort, the histologic signature
      resulted in an error matrix accuracy of predicted response of 0.75 (95% CI 0.64
      0.83; accuracy P < .001). CONCLUSIONS: In an analysis of PDAC tissue microarray
      specimens, we identified and validated a histologic signature, based on leukocyte
      and stromal factors, that associates with PFS times of patients with resected
      PDACs. Immune cells might affect the composition of the pancreatic stroma to
      affect progression of PDAC. These findings provide new insights into the immune
      response to PDAC.

PMID- 30092177
TI  - Bloodstream infection by mcr-1-harboring Escherichia coli in a cancer patient in
      southern Brazil.

PMID- 30092178
TI  - The effect on the immunology laboratory of the expansion in complement
      therapeutics.
AB  - The approval in the US and Europe of Eculizumab in 2007 marked a change in
      complement therapeutics, and with it the landscape for complement testing in the
      clinical immunology laboratory changed. The change had begun even before that
      when C1-Inhibitor preparations were approved in the 1980s in Europe. There are
      now two classes of approved drugs that may impact the immunology laboratory, with
      two dozen more with novel modalities and potential indications that are in
      various stages of development. Every pathway and about every component of
      complement has been targeted by these drug development programs, and the
      modalities of the drugs in development are diverse. These developments will
      likely result in more laboratories offering more complement testing, so this
      review looks forward to some of those possible changes in testing.

PMID- 30092176
TI  - HBV epidemiology and genetic diversity in an area of high prevalence of hepatitis
      B in southern Brazil.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is a major public health problem in
      Brazil. HBV endemicity is usually moderate to low according to geographic
      regions, and high prevalence of this virus has been reported in people of some
      specific Brazilian counties, including those with a strong influence of Italian
      colonization in southern Brazil. Analysis of HBV diversity and identification of
      the main risk factors to HBV infection are necessary to understand hepatitis B
      epidemiology in these high prevalence regions in southern Brazil. OBJECTIVE: To
      investigate epidemiological characteristics and HBV genotypes and subgenotypes
      circulating in a specific city with high HBV prevalence. METHODS: A cross
      sectional study was performed with 102 HBV chronically infected individuals,
      recruited in reference outpatient clinics for viral hepatitis in a city of high
      HBV prevalence (Bento Goncalves) in Rio Grande do Sul state, Brazil between July
      and December 2010. Socio-demographic, clinical and behavior-related variables
      were collected in a structured questionnaire. HBV serological markers (HBsAg,
      anti-HBc), viral load, genotypes/subgenotypes and drug resistance were evaluated
      and comparatively analyzed among all patients. RESULTS: The HBV infected subjects
      had a mean age of 44.9 (+/-12.2) years, with 86 patients (84.3%) reporting to
      have a family history of HBV infection, 51 (50.0%) to share personal objects, and
      were predominantly of Italian descendants (61; 64.9%). There was a predominance
      of genotype D (49/54; 90.7%), but genotype A was also detected (5/54; 9.3%).
      Subgenotypes D1 (1; 4.7%), D2 (3; 14.3%), and D3 (17; 81.0%) were identified. LAM
      resistant mutation (rtM204I) and ADV-resistant mutations (rtA181V) were detected
      in only one patient each. CONCLUSIONS: These results demonstrate a pivotal role
      of intrafamilial transmission for HBV spreading in this population. Furthermore,
      there is a high prevalence of HBV genotype D in this region.

PMID- 30092179
TI  - On the front lines of the opioid epidemic: Rescue by naloxone.
AB  - Naloxone is a specific, high affinity opioid antagonist that has been used to
      treat suspected or confirmed overdose for more than 40 years. Naloxone use was
      initially confined to an emergency room setting, but the dramatic rise in opioid
      overdose events over the past two decades has, with increasing frequency, shifted
      naloxone use to first responders including police, emergency medical technicians,
      and the friends and family of overdose victims. The opioids responsible for
      overdose events have also evolved, from prescription opioids to heroin and most
      recently, very high potency synthetic opioids such as fentanyl. In 2016,
      synthetic opioids were linked to more overdose fatalities than either
      prescription opioids or heroin. In this review, I will discuss the evolution and
      use of naloxone products by first responders and the development of additional
      rescue medications in response to the unprecedented dangers posed by synthetic
      opioids.

PMID- 30092181
TI  - Massively parallel and multiplex blood group genotyping using next-generation
      sequencing.
AB  - OBJECTIVES: Thirty-six blood group systems are listed by the International
      Society of Blood Transfusion, containing almost 350 antigens. Most of these
      result from a single nucleotide polymorphism (SNP). Serology is the standard
      method for blood group typing. However, this technique has some limitations and
      cannot respond to the growing demand of blood product typing for a large number
      of antigens. Here we describe a blood group genotyping assay directly from whole
      blood samples using Next-Generation Sequencing (NGS), allowing the simultaneous
      identification of 15 SNPs associated with the blood group systems of 95 patients
      in a single run. DESIGN AND METHOD: After an automated DNA extraction, targets
      are amplified by multiplex polymerase chain reaction (PCRm). Two panels
      addressing 9 groups have been developed (MNS, Lutheran, Kell, Duffy, Kidd, Diego,
      Yt, Dombrock, and Colton), one for 8 SNPs, the other for 7 SNPs. For each sample,
      both panels corresponding to 14 amplicons (1 amplicon containing 2 SNPs) are
      pooled. Then a dual-indexed library is generated from each pool by linking
      Illumina adaptors directly onto amplicons, followed by sequencing using the MiSeq
      platform (Illumina). RESULTS: In a single experiment, 95 blood donor samples have
      been sequenced for the genes of interest. Among the 1425 targeted single
      nucleotide polymorphisms, 1420 were identified by sequencing, reflecting a
      coverage of 99.65%. The obtained data shows a good correlation (99% for all SNPs)
      with other blood group typing methods. Depending on the allele pairs analyzed,
      correlations vary between 97.12 and 100%. CONCLUSION: Next-Generation sequencing
      would supplement serological and molecular techniques and, in the near future,
      could replace it with complete and fast results acquisition for pre-screening and
      identification of rare blood bags.

PMID- 30092182
TI  - Is a lack of sleep harming adolescents' academic prospects in the digital age?

PMID- 30092180
TI  - Neuropharmacology of attention.
AB  - Early philosophers and psychologists defined and began to describe attention.
      Beginning in the 1950's, numerous models of attention were developed. This
      corresponded with an increased understanding of pharmacological approaches to
      manipulate neurotransmitter systems. The present review focuses on the knowledge
      that has been gained about these neurotransmitter systems with respect to
      attentional processing, with emphasis on the functions mediated within the medial
      prefrontal cortex. Additionally, the use of pharmacotherapies to treat
      psychiatric conditions characterized by attentional dysfunction are discussed.
      Future directions include developing a more comprehensive understanding of the
      neural mechanisms underlying attentional processing and novel pharmacotherapeutic
      targets for conditions characterized by aberrant attentional processing.

PMID- 30092183
TI  - Atypical Mycobacterial Infection in Anophthalmic Sockets With Porous Orbital
      Implant Exposure.
AB  - PURPOSE: To investigate the clinical features and risk factors of atypical
      mycobacterial infection in anophthalmic sockets with porous orbital implant
      exposure. DESIGN: Case-control study. METHODS: The medical records of all
      patients who had undergone surgical correction of porous orbital implant exposure
      were consecutively reviewed, and the patients were stratified as those with
      atypical mycobacterial infection (AM infection group) and others (non-AM group).
      RESULTS: Five and 21 patients were included in the AM infection and non-AM
      groups, respectively. All patients of the AM infection group had a peg or
      motility coupling post (MCP) and showed implant exposure around it. Following up
      on implant exposure, 2 patients abruptly presented with severe conjunctival
      injection and new lesions such as erythematous nodules or eyelid masses. They
      underwent immediate orbital implant exchange and atypical mycobacterial infection
      was diagnosed. Three patients who were not suspected of having infection
      underwent surgery for orbital implant exposure. Results revealed erythematous
      eyelid nodule or recurrent exposure shortly after surgery and patients were
      diagnosed with atypical mycobacterial infection. In the non-AM group, 7 (33.3%)
      patients underwent insertion of a peg or MCP. Statistical analysis showed that
      the insertion of a peg or MCP was the only risk factor showing a significant
      difference between the 2 groups. CONCLUSIONS: The most important underlying risk
      factor for atypical mycobacterial infection in the anophthalmic socket is thought
      to be peg- or MCP-related exposure of the porous orbital implant. Surgical
      removal of the infected orbital implant and long-term antibiotic medication are
      needed for treatment.

PMID- 30092184
TI  - Gene Expression Profiling and PRAME Status Versus Tumor-Node-Metastasis Staging
      for Prognostication in Uveal Melanoma.
AB  - PURPOSE: To compare the prognostic accuracy of gene expression profiling (GEP)
      combined with PRAME status vs the clinical Tumor-Node-Metastasis (TNM) staging in
      patients with uveal melanoma (UM). DESIGN: Retrospective cohort study. METHODS:
      The study included 240 consecutive patients with UM. Tumors were assessed for GEP
      status (Class 1 or Class 2) using a validated 15-gene assay and PRAME expression
      status using quantitative polymerase chain reaction. TNM staging was according to
      the American Joint Committee on Cancer 8th edition. Statistical analysis included
      univariate and multivariate Cox proportional hazard models. Metastasis was the
      primary endpoint. RESULTS: GEP was Class 1 in 128 (53.3%) cases and Class 2 in
      112 (46.7%) cases. PRAME status was negative in 157 (65.4%) cases and positive in
      83 (34.6%) cases. TNM was stage I in 26 (10.8%) cases, IIA in 67 (27.9%) cases,
      IIB in 50 (20.8%) cases, IIIA in 59 (24.6%) cases, and IIIB in 38 (15.8%) cases.
      Metastatic disease was detected in 59 (24.6%) cases after median follow-up of 29
      months (mean 42 months; range 1-195 months). Variables associated with metastasis
      included (in order of decreasing significance): GEP class (P = 1.5 * 10-8),
      largest basal tumor diameter (P = 2.5 * 10-6), PRAME status (P = 2.6 * 10-6), and
      TNM stage (P = 3.7 * 10-6). The prognostic accuracy of an optimized 3-category
      GEP/PRAME model (P = 8.6 * 10-14) was superior to an optimized TNM model (P = 1.3
      * 10-5). CONCLUSIONS: In UM, molecular prognostic testing using GEP and PRAME
      provides prognostic accuracy that is superior to TNM staging.

PMID- 30092185
TI  - Possible Autocrine Function of Galectin-3 in Pancreatic Stellate Cells.

PMID- 30092186
TI  - Association Between Proton Pump Inhibitor Use and Risk of Stroke.

PMID- 30092188
TI  - Re: NSAID Use and Pancreatic Cancer Risk.

PMID- 30092187
TI  - Efficacy of Laparoscopic Nissen Fundoplication vs Transoral Incisionless
      Fundoplication or Proton Pump Inhibitors in Patients With Gastroesophageal Reflux
      Disease: Misleading Ranking Probabilities in Network Meta-analysis.

PMID- 30092190
TI  - Viperin Poisons Viral Replication.
AB  - Control of virus infection relies on the stimulation of interferon-stimulated
      genes (ISGs) that inhibit viral replication. In a recent Nature paper, Gizzi et
      al. (2018) discovered that the ISG viperin inhibits virus replication by
      generating the ribonucleotide ddhCTP, which interferes with RNA synthesis, thus
      offering insights into drug design.

PMID- 30092191
TI  - All Aboard! Enteric Viruses Travel Together.
AB  - Individual virus particles have long been accepted as the infectious unit during
      cellular infection and host-to-host transmission. In this issue of Cell Host &
      Microbe, Santiana et al. (2018) uncover vesicle-cloaked rotavirus and norovirus
      clusters in feces of infected hosts that are more infectious than free virus
      particles during fecal-oral transmission.

PMID- 30092192
TI  - Strength through Organization: Classifying Antibody Activity against EBOV.
AB  - In this issue of Cell Host & Microbe and in a related Cell paper, works by Gunn
      et al. (2018) and Saphire et al. (2018) describe a large number of monoclonal
      antibodies against Ebola virus (EBOV) and correlate their activity with in vivo
      protection.

PMID- 30092193
TI  - HVEM LIGHTs the Way for ILC3s.
AB  - The early response to bacterial infection requires cytokine responses by immune
      cells. In this issue of Cell Host & Microbe, Seo et al. (2018) demonstrate that
      TNF-TNFR superfamily molecules LIGHT and HVEM stimulate early IFN-gamma
      production by type 3 innate lymphoid cells, which are critical for defense
      against Yersinia enterocolitica.

PMID- 30092194
TI  - Bacterial Prison Break: A Host Protein Mimic Paves the Way.
AB  - The intracellular pathogen Francisella secretes effector proteins inside host
      cells; however, their functions have remained unclear. In this issue of Cell Host
      & Microbe, Ledvina et al. (2018) elucidate the role of one such effector, OpiA,
      to be a bacterial phosphatidylinositol-3-kinase that alters phagosomal
      trafficking and can promote intracellular bacterial replication.

PMID- 30092195
TI  - Engineered Bacteria for Cholera Prophylaxis.
AB  - Over 1.3 billion persons are at risk for cholera globally. Vaccination campaigns
      are growing, but intervention options providing nearly immediate protection are
      also needed. Two recent papers in Science Translational Medicine describe
      probiotic bacteria that reduce intestinal colonization in animal models and show
      promise for development as prophylaxis agents.

PMID- 30092196
TI  - Enhancing Rotavirus Vaccination: A Microbial Fix?
AB  - Oral rotavirus vaccines have consistently underperformed in low-income countries.
      In this issue of Cell Host & Microbe,Harris et al. (2018b) explore whether
      vaccine response can be enhanced via antibiotic-mediated modification of the
      bacterial microbiota.

PMID- 30092197
TI  - Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine
      Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial.
AB  - Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by
      rotavirus (RV) but have decreased effectiveness in low- and middle-income
      settings. This proof-of-concept, randomized-controlled, open-label trial tested
      if microbiome modulation can improve RVV immunogenicity. Healthy adults were
      randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin,
      metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then
      vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in
      all subjects. Although antibiotics did not alter absolute anti-RV IgA titers, RVV
      immunogenicity was boosted at 7 days in the narrow-spectrum group. Further,
      antibiotics increased fecal shedding of RV while also rapidly altering gut
      bacterial beta diversity. Beta diversity associated with RVV immunogenicity
      boosting at day 7 and specific bacterial taxa that distinguish RVV boosters and
      RV shedders were identified. Despite the negative primary endpoint, this study
      demonstrates that microbiota modification alters the immune response to RVV and
      supports further exploration of microbiome manipulation to improve RVV
      immunogenicity.

PMID- 30092199
TI  - A Role for Fc Function in Therapeutic Monoclonal Antibody-Mediated Protection
      against Ebola Virus.
AB  - The recent Ebola virus (EBOV) epidemic highlighted the need for effective
      vaccines and therapeutics to limit and prevent outbreaks. Host antibodies against
      EBOV are critical for controlling disease, and recombinant monoclonal antibodies
      (mAbs) can protect from infection. However, antibodies mediate an array of
      antiviral functions including neutralization as well as engagement of Fc-domain
      receptors on immune cells, resulting in phagocytosis or NK cell-mediated killing
      of infected cells. Thus, to understand the antibody features mediating EBOV
      protection, we examined specific Fc features associated with protection using a
      library of EBOV-specific mAbs. Neutralization was strongly associated with
      therapeutic protection against EBOV. However, several neutralizing mAbs failed to
      protect, while several non-neutralizing or weakly neutralizing mAbs could
      protect. Antibody-mediated effector functions, including phagocytosis and NK cell
      activation, were associated with protection, particularly for antibodies with
      moderate neutralizing activity. This framework identifies functional correlates
      that can inform therapeutic and vaccine design strategies against EBOV and other
      pathogens.

PMID- 30092198
TI  - Vesicle-Cloaked Virus Clusters Are Optimal Units for Inter-organismal Viral
      Transmission.
AB  - In enteric viral infections, such as those with rotavirus and norovirus,
      individual viral particles shed in stool are considered the optimal units of
      fecal-oral transmission. We reveal that rotaviruses and noroviruses are also shed
      in stool as viral clusters enclosed within vesicles that deliver a high inoculum
      to the receiving host. Cultured cells non-lytically release rotaviruses and
      noroviruses inside extracellular vesicles. In addition, stools of infected hosts
      contain norovirus and rotavirus within vesicles of exosomal or plasma membrane
      origin. These vesicles remain intact during fecal-oral transmission and thereby
      transport multiple viral particles collectively to the next host, enhancing both
      the MOI and disease severity. Vesicle-cloaked viruses are non-negligible
      populations in stool and have a disproportionately larger contribution to
      infectivity than free viruses. Our findings indicate that vesicle-cloaked viruses
      are highly virulent units of fecal-oral transmission and highlight a need for
      antivirals targeting vesicles and virus clustering.

PMID- 30092201
TI  - LIGHT-HVEM Signaling in Innate Lymphoid Cell Subsets Protects Against Enteric
      Bacterial Infection.
AB  - Innate lymphoid cells (ILCs) are important regulators of early infection at
      mucosal barriers. ILCs are divided into three groups based on expression
      profiles, and are activated by cytokines and neuropeptides. Yet, it remains
      unknown if ILCs integrate other signals in providing protection. We show that
      signaling through herpes virus entry mediator (HVEM), a member of the tumor
      necrosis factor (TNF) receptor superfamily, in ILC3 is important for host defense
      against oral infection with the bacterial pathogen Yersinia enterocolitica. HVEM
      stimulates protective interferon-gamma (IFN-gamma) secretion from ILCs, and mice
      with HVEM-deficient ILC3 exhibit reduced IFN-gamma production, higher bacterial
      burdens and increased mortality. In addition, IFN-gamma production is critical as
      adoptive transfer of wild-type but not IFN-gamma-deficient ILC3 can restore
      protection to mice lacking ILCs. We identify the TNF superfamily member, LIGHT,
      as the ligand inducing HVEM signals in ILCs. Thus HVEM signaling mediated by
      LIGHT plays a critical role in regulating ILC3-derived IFN-gamma production for
      protection following infection. VIDEO ABSTRACT.

PMID- 30092203
TI  - The Role of Emotional Intelligence in Community Integration and Return to Work
      After Acquired Brain Injury.
AB  - OBJECTIVE: To investigate whether emotional intelligence (EI) skills measured via
      the Perceiving, Understanding, and Managing Emotions branches of the Mayer
      Salovey-Caruso Emotional Intelligence Test V2.0 are associated with community
      integration (CI) and return to work (RTW) after moderate-to-severe acquired brain
      injury (ABI), after accounting for other established predictors. DESIGN:
      Retrospective cohort study. SETTING: Outpatient follow-up services within 2
      specialist ABI rehabilitation centers in Melbourne, Australia. PARTICIPANTS:
      Individuals (N=82) with moderate-to-severe ABI discharged from inpatient
      rehabilitation and living in the community (2mo to 7y postinjury). INTERVENTION:
      Not applicable. MAIN OUTCOME MEASURES: Community Integration Questionnaire scores
      for the total sample (N=82; age range 18-80) and RTW status (employed vs not
      employed) for the subset of participants employed prior to ABI (n=71; age range
      19-66). RESULTS: Hierarchical logistic and multiple regression analyses were used
      to examine the unique contribution of Perceiving, Understanding, and Managing
      Emotions scores to RTW and CI, after controlling for demographic, injury-related,
      psychological, and cognitive predictors. As a set, the 3 EI variables did not
      explain incremental variance in outcomes. However, individually, Understanding
      Emotions predicted RTW (adjusted odds ratio=3.10, P=.03), chi2 (12)=35.52,
      P<.001, and Managing Emotions predicted CI (beta=0.23, P=.036), F12,69=5.14,
      P<.001. CONCLUSION: Although the EI constructs in combination did not improve
      prediction beyond the effects of established variables, individual components of
      strategic EI may be important for specific participation outcomes after ABI.

PMID- 30092200
TI  - Species-Specific Deamidation of cGAS by Herpes Simplex Virus UL37 Protein
      Facilitates Viral Replication.
AB  - Herpes simplex virus 1 (HSV-1) establishes infections in humans and mice, but
      some non-human primates exhibit resistance via unknown mechanisms. Innate immune
      recognition pathways are highly conserved but are pivotal in determining
      susceptibility to DNA virus infections. We report that variation of a single
      amino acid residue in the innate immune sensor cGAS determines species-specific
      inactivation by HSV-1. The HSV-1 UL37 tegument protein deamidates human and mouse
      cGAS. Deamidation impairs the ability of cGAS to catalyze cGAMP synthesis, which
      activates innate immunity. HSV-1 with deamidase-deficient UL37 promotes robust
      antiviral responses and is attenuated in mice in a cGAS- and STING-dependent
      manner. Mutational analyses identified a single asparagine in human and mouse
      cGAS that is not conserved in many non-human primates. This residue underpins
      UL37-mediated cGAS deamidation and species permissiveness of HSV-1. Thus, HSV-1
      mediates cGAS deamidation for immune evasion and exploits species sequence
      variation to disarm host defenses.

PMID- 30092204
TI  - Four-Meter Gait Speed: Normative Values and Reliability Determined for Adults
      Participating in the NIH Toolbox Study.
AB  - OBJECTIVES: To establish reference values and determine test-retest reliability
      for usual and maximal 4-meter gait speed. DESIGN: Cross-sectional observational
      study. SETTING: Offices in 10 geographically dispersed cities in the United
      States. PARTICIPANTS: Men and women (N=1320), aged 18 to 85 years, enrolled in
      the National Institutes of Health Toolbox norming study. INTERVENTION: Not
      applicable. MAIN OUTCOME MEASURES: Specifically used were data from men and women
      who were timed over 4 meters (after a static start) while walking at their usual
      and maximum speeds. Norms for usual and maximum gait speed were derived using
      data from 1320 participants. Test-retest reliability for 164 participants was
      described using paired t tests, intraclass correlation coefficients (ICCs), and
      minimal detectable changes (MDCs). RESULTS: Mean usual speed was 1.12 meters per
      second, whereas mean maximum speed was 1.61 meters per second. As a general
      linear model showed 4-meter gait speed to differ significantly according to gait
      condition (speed), sex, and age group; estimates of normal were calculated
      accordingly. The usual speed of 80- to 85-year-old women was lowest at 0.95
      meters per second; the maximum speed of 18- to 29-year-old men was highest at
      1.85 meters per second. Test-retest measures did not differ significantly, but
      the ICCs were only fair and the MDCs were high. CONCLUSIONS: Normative reference
      values provided herein may be helpful in interpreting measurements of 4-meter
      gait speed obtained from adult men and women. The limited reliability of the gait
      speed measurements, however, limits their usefulness in making judgments
      regarding change.

PMID- 30092202
TI  - An Atlas of Genetic Variation Linking Pathogen-Induced Cellular Traits to Human
      Disease.
AB  - Pathogens have been a strong driving force for natural selection. Therefore,
      understanding how human genetic differences impact infection-related cellular
      traits can mechanistically link genetic variation to disease susceptibility. Here
      we report the Hi-HOST Phenome Project (H2P2): a catalog of cellular genome-wide
      association studies (GWAS) comprising 79 infection-related phenotypes in response
      to 8 pathogens in 528 lymphoblastoid cell lines. Seventeen loci surpass genome
      wide significance for infection-associated phenotypes ranging from pathogen
      replication to cytokine production. We combined H2P2 with clinical association
      data from patients to identify a SNP near CXCL10 as a risk factor for
      inflammatory bowel disease. A SNP in the transcriptional repressor ZBTB20
      demonstrated pleiotropy, likely through suppression of multiple target genes, and
      was associated with viral hepatitis. These data are available on a web portal to
      facilitate interpreting human genome variation through the lens of cell biology
      and should serve as a rich resource for the research community.

PMID- 30092205
TI  - Increase in Lactate Without Change in Nutritive Blood Flow or Glucose at Active
      Trigger Points Following Massage: A Randomized Clinical Trial.
AB  - OBJECTIVE: To investigate changes in nutritive blood flow as well as interstitial
      glucose and lactate within an active myofascial trigger point (MTrP) following
      massage. DESIGN: Randomized, placebo-controlled trial. SETTING: Subjects were
      recruited from the general population; procedures were conducted at a research
      center affiliated with a university hospital. PARTICIPANTS: Adults (N=25) (18-49y
      old) with episodic or chronic tension-type headache and an active MTrP in the
      upper trapezius muscle. INTERVENTIONS: Subjects were randomized to receive a
      single trigger point (TrP) release massage or sham ultrasound (US) treatment at
      an active MTrP in the upper trapezius muscle. Microdialysis was used to
      continuously sample interstitial fluid from the MTrP before, during, and for 60
      minutes following intervention. MAIN OUTCOME MEASURES: The primary outcome
      measure was nutritive blood flow within the MTrP as measured by microdialysis
      ethanol clearance; secondary measures included dialysate glucose, dialysate
      lactate, and subject discomfort with the procedures. Pressure-pain threshold
      (PPT) was determined to assess treatment effectiveness. RESULTS: There was no
      treatment effect of TrP release massage on nutritive blood flow (P=.663) or
      dialysate glucose (P=.766). The interaction for lactate was significant
      indicating that dialysate lactate increased for TrP release massage vs sham US
      (P=.04); maximum lactate increase over baseline was observed at 60 minutes after
      TrP release massage (P=.007, 0.128 MUM, 95% confidence interval 0.045-0.212).
      Pain evoked by probe placement into an active MTrP was low. An interaction effect
      on PPT was significant (P=.005). CONCLUSION: TrP release massage of an active
      MTrP affected anaerobic metabolism as represented by an increase in dialysate
      lactate without change in nutritive blood flow or dialysate glucose. The lack of
      a treatment effect on blood flow is discussed.

PMID- 30092206
TI  - The Effects of M2M and Adapted Yoga on Physical and Psychosocial Outcomes in
      People With Multiple Sclerosis.
AB  - OBJECTIVE: To investigate the effects of two 12-week exercise training
      interventions, movement-to-music (M2M) and adapted yoga (AY), on physical and
      psychosocial outcomes in people with multiple sclerosis (MS). DESIGN: Three-arm
      randomized controlled proof-of-concept trial. SETTING: A community-based fitness
      facility. PARTICIPANTS: Participants (N=81) with MS (Patient Determined Disease
      Steps [PDDS] self-reported disease status scores: 0-6) between ages of 18 and 65
      years were randomized to M2M (n=27), AY (n=26), or waitlist control (n=28).
      INTERVENTIONS: Both M2M and AY completed three 60-minute exercise sessions per
      week for 12 weeks. Waitlist controls received biweekly newsletters via mail that
      contained educational information on living with MS. MAIN OUTCOME MEASURES:
      Primary measures were timed Up and Go (TUG, s) test, 6-minute walk test (6MWT,
      m), and 5 times sit-to-stand test (FTSST, s). Secondary measures were self
      reported outcomes assessed using Patient-Reported Outcomes Measurement
      Information System Fatigue and Pain Interference Short Form 8a. Participants were
      evaluated at baseline and postintervention. Primary analyses were performed using
      an intent-to-treat mixed model analysis of covariance. RESULTS: Comparisons
      across all 3 groups revealed significant group differences in TUG and 6MWT. Post
      hoc analyses indicated significant improvements in TUG (least square mean
      difference [95% confidence interval] = -1.9s [-3.3 to -0.5], P=.01, d=0.7) and
      6MWT (41.0m [2.2-80.0], P=.04, d=0.6; controlled for PDDS) in M2M compared to
      controls, while no significant differences were observed when compared AY to
      controls. No significant group differences were found in FTSST, fatigue, and pain
      interference. CONCLUSIONS: M2M may be a useful and enjoyable exercise form for
      people with MS in improving mobility and walking endurance and merits long-term
      study in larger study populations.

PMID- 30092207
TI  - Liquid biopsies to guide therapeutic decisions in rheumatoid arthritis.
AB  - Rheumatoid arthritis (RA) is a systemic, immune-mediated inflammatory disease
      that has transitioned from a debilitating disease to a chronic, controllable
      disease. This has been possible due to the introduction of new treatment
      strategies like "treat-to-target," in which the clinician treats the patient
      aggressively enough to reach low disease activity or remission, and the
      introduction of new therapeutic agents, such as biological therapies, which can
      lead to the prevention of damage by early diagnosis and initiation of treatment.
      Attention is now being directed toward identifying the optimal treatment for each
      patient, one that will be the most efficient and have the least number of side
      effects. Much work has been done to find serologic and synovial biomarkers of
      response to various RA treatments. Proteomics, genomics and, in the past few
      years, metabolomics, have all been used in the quest of identifying these
      biomarkers. Blood-based liquid biopsies provide a minimally invasive alternative
      to synovial biopsies to identify cellular and molecular signatures that can be
      used to longitudinally monitor response and allow for personalized medicine
      approach. Liquid biopsies are comprised of cell-free DNA, immune circulating
      cells, and extracellular vesicles, and are being increasingly and successfully
      used in the field of oncology for diagnosis, progression, prognosis, and
      prediction of response to treatment. Recently, researchers have also begun
      investigating the usefulness of liquid biopsies in the field of rheumatology; in
      this review, we will focus on the potential of liquid biopsy blood samples as
      biomarkers of response to treatment in patients with RA.

PMID- 30092208
TI  - Small RNAs, but Sizable Itch: TRPA1 Activation by an Extracellular MicroRNA.
AB  - Chronic itch is a major symptom of cutaneous T cell lymphoma (CTCL). In this
      issue of Neuron, Han and colleagues (2018) provide evidence that one of the itch
      mediators in CTCL is an extracellular miRNA that directly activates TRPA1 on
      sensory neurons.

PMID- 30092209
TI  - A New Twist on Tip Links.
AB  - Auditory transduction is fast and sensitive owing to the direct detection of
      mechanical stimuli by hair cells, the sensory receptors of the internal ear. A
      study by Dionne et al. (2018) in this issue of Neuron suggests how signals
      propagate through tip links, the cadherin-based strands that gate mechanically
      sensitive channels.

PMID- 30092210
TI  - Hippocampal Mossy Cells Provide a Fate Switch for Adult Neural Stem Cells.
AB  - The pathways that convert neural stem cells (NSCs) into functional neurons in the
      adult hippocampus are tightly regulated. In this issue of Neuron, Yeh et al.
      (2018) demonstrate that the activity of dentate mossy cells determines the
      balance between quiescence and activation of NSCs.

PMID- 30092211
TI  - And the Band Keeps Marching On.
AB  - Before the onset of hearing, activity in the developing auditory system is
      dominated by periodic bursts of action potentials that originate in the cochlea
      from where they propagate up the central auditory pathway. In this issue of
      Neuron, Babola et al. (2018) provide new insight into the spatiotemporal
      organization of prehearing activity in vivo and its homeostatic control.

PMID- 30092212
TI  - The CeNGEN Project: The Complete Gene Expression Map of an Entire Nervous System.
AB  - Differential gene expression defines individual neuron types and determines how
      each contributes to circuit physiology and responds to injury and disease. The C.
      elegans Neuronal Gene Expression Map & Network (CeNGEN) will establish a
      comprehensive gene expression atlas of an entire nervous system at single-neuron
      resolution.

PMID- 30092214
TI  - Supramammillary Nucleus Modulates Spike-Time Coordination in the Prefrontal
      Thalamo-Hippocampal Circuit during Navigation.
AB  - During navigation, hippocampal spatial maps are thought to interact with action
      planning systems in other regions of cortex. We here report a key role for spike
      time coordination in functional coupling of the medial prefrontal cortex (mPFC)
      to the hippocampus through the thalamic nucleus reuniens (NR). When rats perform
      a T-maze alternation task, spikes of neurons in mPFC and NR exhibit enhanced
      coordination to the CA1 theta rhythm before the choice point on the maze. A
      similar coordination to CA1 theta rhythm was observed in neurons of the
      supramammillary nucleus (SUM). Optogenetic silencing of SUM neurons reduced the
      temporal coordination in the mPFC-NR-CA1 circuit. Following SUM inactivation,
      trajectory representations were impaired in both NR and CA1, but not in mPFC,
      indicating a failure in transmission of action plans from mPFC to the
      hippocampus. The findings identify theta-frequency spike-time coordination as a
      mechanism for gating of information flow in the mPFC-NR-CA1 circuit.

PMID- 30092215
TI  - Structuring of Abstract Working Memory Content by Fronto-parietal Synchrony in
      Primate Cortex.
AB  - How is neuronal activity across distant brain regions orchestrated to allow
      multiple stimuli to be stored together in working memory, yet maintained separate
      for individual readout and protection from distractors? Using paired recordings
      in the prefrontal and parietal cortex of monkeys discriminating numbers of items
      (numerosities), we found that working memory content is structured by frequency
      specific oscillatory synchrony. Parieto-frontal signaling in the beta band
      carried information about the most recent numerical input. Fronto-parietal
      coupling in the theta band differentiated between multiple memorized
      numerosities. Task-relevant and distracting stimuli were nested in spiking
      activity of single prefrontal neurons, but could be separated by reading out
      spikes at distinct phases of parietal theta oscillations. The strength of phase
      locked, cross-regional memory coding predicted task performance. Frequency
      specific communication channels in the fronto-parietal network could enable
      serial bottom-up and parallel top-down information transmission, providing an
      important mechanism to protect working memory from interference.

PMID- 30092216
TI  - Use of a Non-Crosslinked Collagen Membrane During Guided Bone Regeneration Does
      Not Interfere With the Bone Regenerative Capacity of the Periosteum.
AB  - PURPOSE: To assess whether the use of a non-crosslinked porcine collagen type I
      and III bi-layered membrane inter-positioned between the periosteum and a bone
      defect would interfere with the bone regenerative capacity of the periosteum.
      MATERIALS AND METHODS: Sixty rats, each with 1 critical-size calvarial defect
      (CSD; diameter, 5 mm) in the parietal bone, were randomly allocated to 1 of 3
      equal-size groups after CSD creation: 1) the periosteum was excised and the flap
      was repositioned without interposition of a membrane (no-periosteum [NP] group);
      2) the flap including the periosteum was repositioned (periosteum [P] group); and
      3) a non-crosslinked collagen membrane was inter-positioned between the flap,
      including the periosteum, and the bone defect (membrane [M] group). Micro
      computed tomography, qualitative histology, immunohistochemistry, and reverse
      transcription real-time quantitative polymerase chain reaction were performed at
      3, 7, 15, and 30 days postoperatively. RESULTS: A markedly increased radiographic
      residual defect length was observed in the NP group compared with the P group at
      30 days. The NP group also presented a smaller radiographic bone fill area than
      the P group at 15 and 30 days and then the M group at 30 days. The P and M groups
      exhibited considerably greater expression of bone morphogenetic protein-2 and
      osteocalcin than the NP group at 7 days; expression of transforming growth factor
      beta1 was considerably greater in the NP group at 15 days. Further, the P group
      presented considerably higher gene expression levels of Runx2 and Jagged1 at 7
      days and of alkaline phosphatase at 3 and 15 days compared with the M and NP
      groups. CONCLUSION: Interposition of this specific non-crosslinked collagen
      membrane between the periosteum and the bone defect during guided bone
      regeneration interferes only slightly, if at all, with the bone regenerative
      capacity of the periosteum.

PMID- 30092213
TI  - Economic Choice as an Untangling of Options into Actions.
AB  - We propose that economic choice can be understood as a gradual transformation
      from a domain of options to one of the actions. We draw an analogy with the idea
      of untangling information in the form vision system and propose that form vision
      and economic choice may be two aspects of a larger process that sculpts actions
      based on sensory inputs. From this viewpoint, choice results from the accumulated
      effect of repetitions of simple computations. These may consist primarily of
      relative valuations (evaluations relative to the value of rejection, perhaps in a
      manner akin to divisive normalization) applied to individual offers. With regard
      to economic choice, cortical brain regions differ primarily in their position and
      in what information they prioritize, and do not-with a few exceptions-have
      categorically distinct roles. Each region's specific contribution is determined
      largely by its inputs; thus, understanding connectivity is crucial for
      understanding choice. This view suggests that there is no single site of choice,
      that there is no meaningful distinction between pre- and post-decisionality, and
      that there is no explicit representation of value in the brain.

PMID- 30092217
TI  - Accuracy of Virtual Surgical Planning in Treatment of Temporomandibular Joint
      Ankylosis Using Distraction Osteogenesis: Comparison of Planned and Actual
      Results.
AB  - PURPOSE: This study evaluated the accuracy of virtual surgical planning and 3
      dimensional (3D) printed templates to guide osteotomy and distraction
      osteogenesis (DO) in the treatment of temporomandibular joint (TMJ) ankylosis and
      secondary mandibular deformity. PATIENTS AND METHODS: Seven consecutive patients
      diagnosed with TMJ ankylosis and mandibular deformities were included. A
      composite skull model was obtained with data from spiral computed tomography (CT)
      and laser scanning of the dental arch. A virtual surgical simulation was
      performed using Dolphin Imaging 11.7 Premium (Dolphin Imaging and Management
      Solutions, Chatsworth, CA). Then, the virtual plan was transferred to the
      operation using 2 surgical templates. These templates were designed by 3D
      printing using data from the virtual surgical simulation for guiding the
      osteotomy and the DO, respectively. The preoperative measurement and differences
      between the actual mandibular position and the virtual plan were analyzed.
      RESULTS: Postoperative radiographs, CT images, and quantitative analysis showed a
      clinically acceptable precision for the position of the mandible. The mean length
      of the mandible and the vertical height of the DO were 79.1 and 14.9 mm,
      respectively. With the 3D superimposition and linear measurement, the mean
      difference between the virtual plan and the actual results ranged from 0.64 +/-
      0.20 to 1.90 +/- 0.85 mm. All patients obtained satisfactory changes in the
      facial profile and marked improvement in postoperative pharyngeal airway space
      and mouth opening. CONCLUSION: The results of this study showed that virtual
      surgical planning and 3D printed guiding templates facilitated treatment
      planning, an accurate osteotomy, repositioning of bony segments, and contouring
      of the mandibular border in the treatment of TMJ ankylosis and secondary
      mandibular deformity.

PMID- 30092218
TI  - CXCR3 expression in colorectal cancer cells enhanced invasion through preventing
      CXCR4 internalization.
AB  - One of the major causes of death in colorectal cancer (CRC) is invasion and
      metastasis. Better understanding of the molecular mechanism of CRC invasion and
      metastasis is essential in developing effective cancer therapies. Cooperative
      effect of CXCR3 and CXCR4 plays a crucial role in regulating CRC invasion. In
      present study, we discovered that CRC cells expressing higher levels of CXCR3 and
      CXCR4 were more invasive. Additionally, CXCR3 formed heteromers with CXCR4 and
      retained CXCR4 on cell surface. CXCR3 knockdown reduced surface CXCR4 expression
      and partially inhibited CRC cell invasion. On the contrary, CXCR3 overexpression
      enhanced surface CXCR4 abundance and promoted CRC cell invasion. Further research
      indicated that CXCR3-A isoform was responsible for increased CXCR4 surface
      expression and CRC cell invasion. However, CXCR3-A overexpression without CXCR4
      expression did not cause CRC cell invasion, which suggested that CXCR3-A
      indirectly affect cell invasion through regulating CXCR4. Taken together, CXCR3
      enhanced CXCR4 function in CRC cell invasion through forming heteromers with
      CXCR4 on cell surface and prevent CXCR4 internalization. Therefore, targeting
      CXCR3 could be a promising strategy for clinical treatment of CRC cell invasion
      and metastasis.

PMID- 30092219
TI  - The p75 neurotrophin receptor enhances HIF-dependent signaling in glioma.
AB  - Tumor hypoxia is associated with several features of aggressive glioma growth,
      including migration, invasion, and stemness. Most of the cellular adaptation to
      hypoxia is mediated by the hypoxia-inducible factors HIF-1alpha and HIF-2alpha,
      but regulation of these factors by both oxygen-dependent and -independent
      mechanisms in brain tumors is only partially understood. Here, we show that the
      p75 neurotrophin receptor (p75NTR) is stabilized at hypoxia in murine glioma in
      vivo, as well as in primary human glioma cultures in vitro. Expression of p75NTR
      resulted in increased stabilization of HIF-1alpha and HIF-2alpha, and RNAi or
      pharmacologic targeting of p75NTR diminished HIF stabilization and HIF-dependent
      signaling at hypoxia. Consequentially, p75NTR inhibition resulted in decreased
      migration, invasion, and stemness in response to hypoxia, suggesting that p75NTR
      is a central regulator of hypoxia-induced glioma aggressiveness. Together, our
      findings support the literature that identifies p75NTR as a potential therapeutic
      target in brain tumors.

PMID- 30092220
TI  - Cerebrospinal fluid from Alzheimer patients affects cell-mediated nerve growth
      factor production and cell survival in vitro.
AB  - Alzheimer's disease (AD) is characterized by early degeneration of cholinergic
      neurons and decreased levels of nerve growth factor (NGF). Thus, increasing the
      NGF levels by for instance encapsulated cell bio-delivery (ECB) is a potential
      treatment strategy. The results from our previous first-in-human studies on ECB
      of NGF to the basal forebrain cholinergic neurons were promising, but indicated
      some variability of long-term viability of the encapsulated cells and associated
      reduced NGF-release. Here we studied the effect of amyloid beta-peptides (Abeta),
      interleukin 1-beta (IL-1beta), and CSF from AD, Lewy body dementia (LBD) or
      subjective cognitive impairment (SCI) patients on the NGF overproducing cell line
      NGC-0295. At physiological concentrations, neither Abeta40 nor Abeta42 had any
      major impact on cell viability or NGF-production. In contrast, IL-1beta dose
      dependently affected NGF-production over time. Exposure of NGF-producing cells to
      CSF from AD patients showed significantly reduced NGF-release as compared to CSF
      from LBD or SCI patients. By mass spectrometry we found 3 proteins involved in
      inflammatory pathways to have an altered expression in AD CSF compared to LBD and
      SCI. Cell survival and NGF-release were not affected by Abeta. NGF-release was
      affected by IL-1beta, suggesting that inflammation has a negative effect on ECB
      cells.

PMID- 30092222
TI  - miR-190 promotes HCC proliferation and metastasis by targeting PHLPP1.
AB  - miRNAs regulate gene expression and enable clinicians to distinguish between
      benign and malignant tissues in cancers. PH domain leucine-rich repeat-containing
      protein phosphatase 1 (PHLPP1) is known to be a tumour suppressor. A lentiviral
      overexpression system was used to stably express miR-190, leading to the
      enhancement of hepatocellular carcinoma (HCC) proliferation and metastasis as a
      result of inhibited PHLPP1 expression. The results showed that stable miR-190
      expression increased the expression of EMT-related proteins (Snail and TCF8/ZEB1)
      as well as the phosphorylation of Akt at Ser473 and the expression of a
      disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1).
      However, restoring PHLPP1 expression counteracted the effects of miR-190 on HCC
      proliferation, migration and invasion. The results of the animal experiments
      showed that miR-190 improved the HepG2 cell tumour formation and lung metastasis
      ability. Stable miR-190 overexpression leads to the downregulation of PHLPP1
      protein expression. miR-190 has potential as a target in the treatment and
      diagnosis of HCC.

PMID- 30092221
TI  - Hippo, Drosophila MST, is a novel modifier of motor neuron degeneration induced
      by knockdown of Caz, Drosophila FUS.
AB  - Mutations in the Fused in Sarcoma (FUS) gene have been identified in familial ALS
      in human. Drosophila contains a single ortholog of human FUS called Cabeza (Caz).
      We previously established Drosophila models of ALS targeted to Caz, which
      developed the locomotive dysfunction and caused anatomical defects in presynaptic
      terminals of motoneurons. Accumulating evidence suggests that ALS and cancer
      share defects in many cellular processes. The Hippo pathway was originally
      discovered in Drosophila and plays a role as a tumor suppressor in mammals. We
      aimed to determine whether Hippo pathway genes modify the ALS phenotype using Caz
      knockdown flies. We found a genetic link between Caz and Hippo (hpo), the
      Drosophila ortholog of human Mammalian sterile 20-like kinase (MST) 1 and 2. Loss
      of-function mutations of hpo rescued Caz knockdown-induced eye- and neuron
      specific defects. The decreased Caz levels in nuclei induced by Caz knockdown
      were also rescued by loss of function mutations of hpo. Moreover, hpo mRNA level
      was dramatically increased in Caz knockdown larvae, indicating that Caz
      negatively regulated hpo. Our results demonstrate that hpo, Drosophila MST, is a
      novel modifier of Drosophila FUS. Therapeutic targets that inhibit the function
      of MST could modify the pathogenic processes of ALS.

PMID- 30092223
TI  - Bio-efficacy of LifeNet, a deltamethrin incorporated long-lasting insecticidal
      net, as assessed in experimental huts against Anopheles fluviatilis, a major
      malaria vector in east-central India.
AB  - LifeNet, a deltamethrin incorporated long-lasting insecticidal (polypropylene)
      net (LLIN), was qualified by the World Health Organization Pesticide Evaluation
      Scheme (WHOPES) for Phase-II trial in India. The purpose of this trial was to
      assess the bio-efficacy of unwashed and 20 and 30 times washed LifeNet in
      comparison to the nets conventionally treated with deltamethrin against the
      natural population of Anopheles fluviatilis, a major malaria vector, in terms of
      deterring hut entry, inhibiting blood feeding, inducing exophily and causing
      mortality. The trial was carried out in six experimental huts constructed at
      Kandhaguda village in Malkangiri district, Odisha State. The efficacy of unwashed
      and washed (20 or 30 times) LifeNet was compared with untreated polypropylene and
      conventionally treated (with deltamethrin) polyester net washed to just before
      exhaustion or washed 20 times. The study showed a significant reduction of entry
      (treatment: 1.61-4.78; control: 7.61 per hut) and an increase in exit (50.7-64.4%
      and 39.1%) of An. fluviatilis in the treated arms compared to the control arm
      (untreated net) (P < 0.05). Blood feeding rates reduced in treated arms (20.7
      68.0%) compared to the control (80.3%) (P < 0.05). Total mortality was
      significantly higher in LifeNet arms (73.8-98.3%) than the control (2.2%) (P <
      0.05). After 30 washes, the active ingredient (AI) retention in LifeNet was 62%.
      Performance of the three LifeNet arms against the susceptible population of An.
      fluviatilis met the WHO efficacy criteria of Phase II evaluation for LLINs.

PMID- 30092224
TI  - Finding a model for the study of Leishmania (Leishmania) mexicana infection: The
      Yucatan Deer mouse (Peromyscus yucatanicus) as a suitable option.
AB  - For more than four decades, the murine model has been employed extensively to
      understand immunological mechanisms associated with Leishmania infection.
      Although the use of laboratory mice has been very informative, mainly for L. (L.)
      major infection, the extrapolation to other Leishmania species and more
      importantly to human disease has been limited. Particularly in the case of L.
      (L.) mexicana, most infected mouse strains are highly susceptible and never
      presented asymptomatic infection, which is the main outcome in human. Thus, we
      postulated the use of Peromyscus yucatanicus, a primary reservoir of L. (L.)
      mexicana in the Yucatan Peninsula of Mexico, as an experimental model to study
      Leishmania infection. This rodent species can produce both asymptomatic and
      clinical infections therefore they seem more appropriate for studying host
      pathogen interactions. In this review, we recapitulate the immunological findings
      observed in the traditional murine model of L. (L.) mexicana highlighting the
      differences with humans' infection and demonstrate the pertinence of P.
      yucatanicus as the experimental model for studying L. (L.) mexicana infection.

PMID- 30092225
TI  - Efficacy of mebendazole in paediatric patients with giardiasis: A systematic
      review and meta-analysis.
AB  - Mebendazole (MBZ), a benzimidazole compound, has received attention in treating
      patients with giardiasis because it has shown beneficial effects both in vitro
      and in vivo. The aim of this study was to assess with a systematic review and
      meta-analysis of randomized controlled trials (RCTs) the efficacy of MBZ compared
      to other antigiardial agents in children. We searched RCTs of MBZ for the
      treatment of Giardia infections published in PubMed and EBSCOhost. Application of
      inclusion and exclusion criteria, data extraction, and assessment of
      methodological quality were independently performed in duplicate. The primary
      outcome was the parasitological cure. We included 7 RCTs in the systematic review
      (639 patients). There was no clinical difference in the parasitological cure
      between MBZ and metronidazole (MTZ). The relative risk (RR) was 0.81 [95%
      Confidence Interval 0.61-1.09], with high heterogeneity (4 trials, I2 = 81%). The
      prediction interval expected to cover the results of a new trial was wide enough
      (0.22-2.96) to support both a clinically relevant difference favouring either MBZ
      or MTZ. The decision to support any treatment should be based not only on
      efficacy but also safety and cost. Although our results suggest that MBZ may be
      an effective treatment option for children with Giardia infection, they should
      also be interpreted and translated into clinical practice with caution, as the
      evidence is based on a limited number of RCTs presenting high heterogeneity.

PMID- 30092226
TI  - North American scorpion species of public health importance with a reappraisal of
      historical epidemiology.
AB  - Scorpionism is a severe threat to public health in North America. Historically,
      few species of Centruroides have been considered to be the offending taxa, but we
      know now that their diversity is greater and our knowledge incomplete. Current
      distribution maps are inadequate for some species. Epidemiologic studies are
      sporadic and local, and a complete synthesis for North America is missing. We
      analyze historical and recent knowledge about the identity, distribution and
      epidemiology of species of medical importance in North America. PubMed, Google
      Scholar, the National Collection of Arachnids, and results of recent field work
      were consulted in the preparation of our analysis. We recognized 21 species and
      one subspecies of medically important scorpions in need of precise geographical
      delimitation. All these species are found in Mexico, which is clearly a hotspot
      for scorpionism. Although mortality has been steadily decreasing, deaths still
      occur, and morbidity remains high. Mortality is most common at age classes of 0
      10 years and >50. Morbidity is highest in age class 15-50 years, including the
      most economically active segment of the population. The season of the highest
      incidence of scorpion sting peaks between spring and summer but there appears to
      be a second, lower peak at the end of the summer. Although the systematics of the
      genus Centruroides has advanced considerably, our knowledge of its diversity
      remains fragmentary. There is a disconnection between the actual distribution of
      the scorpions and the incidence maps constructed from scorpion sting records.
      Despite a historically robust knowledge of the distribution of well-known
      species, most recently described species are known from only a few localities.
      Some of the epidemiological parameters are consistent among studies reported
      herein.

PMID- 30092227
TI  - Lysine glycation of apolipoprotein A-I impairs its anti-inflammatory function in
      type 2 diabetes mellitus.
AB  - Apolipoprotein A-I (apoA-I), the major protein compontent of high-density
      lipoprotein (HDL), exerts many anti-atherogenic functions. This study aimed to
      reveal whether nonenzymatic glycation of specific sites of apoA-I impaired its
      anti-inflammatory effects in type 2 diabetes mellitus (T2DM). LC-MS/MS was used
      to analyze the specific sites and the extent of apoA-I glycation either modified
      by glucose in vitro or isolated from T2DM patients. Cytokine release in THP-1
      monocyte-derived macrophages was tested by ELISA. Activation of NF-kappa B
      pathway was detected by western blot. The binding affinity of apoA-I to THP-1
      cells was measured using 125I-labeled apoA-I. We identified seven specific lysine
      (Lys, K) residues of apoA-I (K12, K23, K40, K96, K106, K107 and K238) that were
      susceptible to be glycated either in vitro or in vivo. Glycation of apoA-I
      impaired its abilities to inhibit the release of TNF-alpha and IL-1beta against
      lipopolysaccharide (LPS) in THP-1 cells. Besides, the glycation levels of these
      seven K sites in apoA-I were inversely correlated with its anti-inflammatory
      abilities. Furthermore, glycated apoA-I had a lower affinity to THP-1 cells than
      native apoA-I had. We generated mutant apoA-I (K107E, M-apoA-I) with a
      substitution of glutamic acid (Glu, E) for lysine at the 107th site, and found
      that compared to wild type apoA-I (WT-apoA-I), M-apoA-I decreased its anti
      inflammatory effects in THP-1 cells. We also modeled the location of these seven
      K residues on apoA-I which allowed us to infer the conformational alteration of
      glycated apoA-I and HDL. In summary, glycation of these seven K residues altered
      the conformation of apoA-I and consequently impaired the protective effects of
      apoA-I, which may partly account for the increased risk of cardiovascular disease
      (CVD) in diabetic subjects.

PMID- 30092229
TI  - Exploring the entry route of palmitic acid and palmitoylcarnitine into myoglobin.
AB  - Myoglobin, besides its role in oxygen turnover, has gained recognition as a
      potential regulator of lipid metabolism. Previously, we confirmed the interaction
      of fatty acids and acylcarnitines with Oxy-Myoglobin, using both molecular
      dynamic simulations and Isothermal Titration Calorimetry studies. However, those
      studies were limited to testing only the binding sites derived from homology to
      fatty acid binding proteins and predictions using automated docking. To explore
      the entry mechanisms of the lipid ligands into myoglobin, we conducted molecular
      dynamic simulations of murine Oxy- and Deoxy-Mb structures with palmitate or
      palmitoylcarnitine starting at different positions near the protein surface. The
      simulations indicated that both ligands readily (under ~10-20 ns) enter the Oxy
      Mb structure through a dynamic area ("portal region") near heme, known to be the
      entry point for small molecule gaseous ligands like O2, CO and NO. The entry is
      not observed with Deoxy-Mb where lipid ligands move away from protein surface,
      due to a compaction of the entry portal and the heme-containing crevice in the Mb
      protein upon O2 removal. The results suggest quick spontaneous binding of lipids
      to Mb driven by hydrophobic interactions, strongly enhanced by oxygenation, and
      consistent with the emergent role of Mb in lipid metabolism.

PMID- 30092228
TI  - Interaction of substrate-mimicking peptides with the AAA+ ATPase ClpB from
      Escherichia coli.
AB  - A molecular chaperone ClpB disaggregates and reactivates aggregated proteins in
      cooperation with DnaK, DnaJ, and GrpE. Within a cellular environment, ClpB must
      distinguish between properly folded and aggregated proteins by recognizing
      specific physical and/or chemical surface properties of the aggregates. However,
      the molecular mechanism of substrate binding to ClpB is poorly understood. We
      hypothesized that ClpB recognizes those polypeptide segments that promote protein
      aggregation because they are likely present at the surface of growing aggregates.
      We used an algorithm TANGO (Fernandez-Escamilla et al., Nat. Biotech. 2004, 22,
      1302) to predict the aggregation-prone segments within the model ClpB-binding
      peptides and investigated interactions of the FITC-labeled peptides with ClpB
      using fluorescence anisotropy. We found that ClpB binds the substrate-mimicking
      peptides with positive cooperativity, which is consistent with an allosteric
      linkage between substrate binding and ClpB oligomerization. The apparent affinity
      towards ClpB for peptides displaying different predicted aggregation propensities
      correlates with the peptide length. However, discrete aggregation-prone segments
      within the peptides are neither sufficient nor necessary for efficient
      interaction with ClpB. Our results suggest that the substrate recognition
      mechanism of ClpB may rely on global surface properties of aggregated proteins
      rather than on local sequence motifs.

PMID- 30092230
TI  - Disrupted migration and proliferation of neuroblasts after postnatal
      administration of angiogenesis inhibitor.
AB  - In adult rodents, neuroblasts originating from the subventricular zone migrate
      tangentially through the rostral migratory stream (RMS) toward the olfactory bulb
      where they differentiate into interneurons. Neuroblasts in the RMS migrate in
      chains for a long distance along specifically arranged blood vessels which
      promote their migration. Although blood vessels in the neurogenic region of the
      forebrain are present early in development, their rearrangement into this
      specific pattern takes place during the first postnatal weeks. Here we examined
      the relevance of this rearrangement to the migration-guiding "scaffold" for the
      neurogenic processes in the RMS such as cell migration and proliferation. To
      disturb the reorganization of blood vessels, endostatin - an inhibitor of
      angiogenesis, was administered systemically to rat pups during the first
      postnatal week. Ten days or three months later, the arrangement of blood vessels,
      migration and proliferation of cells in the RMS were assessed. As we expected,
      the inhibition of angiogenesis disrupted rearrangement of blood vessels in the
      RMS. The rearrangement's failure resulted in a strong disruption of the mode and
      direction of neuroblast migration. Chain migration failed and neuroblasts
      migrated out of the RMS. The inhibition caused a slight increase in the number of
      proliferating cells in the RMS. The consequences were more obvious ten days after
      the inhibition of angiogenesis, although they persisted partly into adulthood.
      Altogether, here we show that the process of rearrangement of blood vessels in
      the RMS during the early postal period is crucial to ensure the regular course of
      postnatal neurogenesis.

PMID- 30092231
TI  - Protective effects of the astaxanthin derivative, adonixanthin, on brain
      hemorrhagic injury.
AB  - Astaxanthin is beneficial for human health and is used as a dietary supplement.
      The present study was performed in order to examine the protective effects of the
      astaxanthin derivative, adonixanthin, against cell death caused by hemoglobin,
      collagenase, lipopolysaccharide, and hydrogen peroxide, which are associated with
      hemorrhagic brain injury. In an in vitro study, adonixanthin exerted
      cytoprotective effects against each type of damage, and its effects were stronger
      than those of astaxanthin. The increased production of reactive oxygen species in
      human brain endothelial cells in the hemoglobin treatment group was inhibited by
      adonixanthin. Moreover, adonixanthin suppressed cell death in SH-SY5Y cells. In
      an in vivo study, the oral administration of adonixanthin improved blood-brain
      barrier hyper-permeability in an autologous blood ICH model. We herein
      demonstrated for the first time that adonixanthin exerted protective effects
      against hemorrhagic brain damage by activating antioxidant defenses, and has
      potential as a protectant against intracerebral hemorrhage.

PMID- 30092232
TI  - Hemopexin reduces blood-brain barrier injury and protects synaptic plasticity in
      cerebral ischemic rats by promoting EPCs through the HO-1 pathway.
AB  - Ischemic stroke causes endothelial dysfunction and blood-brain barrier
      dysfunction, thus damages synaptic plasticity such as learning and memory. In
      this study we aim to investigate the effect of hemopexin (HPX) in protecting
      synaptic plasticity and blood brain barrier integrity from toxic heme, and
      determine whether this effect is via the activation of endothelial progenitor
      cells (EPCs) through the heme oxygenase-1 (HO-1) pathway. Our data indicates HPX
      showed a significant effect in inducing the expression of HO-1, promoting the
      migration and differentiation of EPCs, facilitating new blood vessel formation
      thus protecting blood-brain barrier integrity. Also the magnitude of synaptic
      plasticity of rats recovered with HPX treatment. And in the presence of HO-1
      blocker Zinc protoporphyrin-9 (ZnppIX), HPX lost its protective effect. This
      suggests that HPX protects endothelial and blood brain barrier integrity from
      toxic heme, thus protects neurologic function in cerebral ischemic rats in HO-1
      pathway.

PMID- 30092233
TI  - Feeding behavior in three-year-old children born <30 weeks and term-born peers.
AB  - BACKGROUND: Feeding difficulties threaten growth, health and neurodevelopment,
      and are prevalent among infants born preterm. The literature differs on (i)
      whether these problems persist into early childhood, and (ii) risk factors in the
      preterm population. In this study we explore feeding difficulties and risk
      factors in preterm and term-born three-year-olds. OBJECTIVES: To determine
      whether three-year-olds born <30 weeks have poorer feeding outcomes than their
      term-born peers; and identify predictors of feeding outcomes in children born <30
      weeks. METHODS: Feeding outcomes were examined in three-year-old children born
      <30 weeks, and a term-born comparison group, using parent report and the
      Behavioral Pediatric Feeding Assessment Scale (BPFAS). Factors hypothesized to be
      associated with feeding difficulties and preterm birth were examined in the
      preterm group, including: gestational age at birth, birth weight z-score, chronic
      lung disease (CLD), nasogastric tube (NGT) feeding at hospital discharge, age at
      breastfeeding cessation, oromotor feeding impairment at 12 months, weight at 12
      months in kilograms and neurodevelopmental diagnoses. RESULTS: In 217 children
      (111 born <30 weeks, 106 term-born), parents of children born <30 weeks reported
      more feeding concerns on parent report questions than parents of term-born peers.
      CLD, NGT at discharge, neurodevelopmental diagnoses and weight at 12 months
      predicted these parent-reported outcomes. By contrast, there was no difference in
      BPFAS results between preterm and term groups, and BPFAS scores were predicted
      only by birth-weight z-score in the preterm group. CONCLUSIONS: Behavioral
      feeding outcomes for three-year-old children born <30 weeks were equivalent to
      term-born peers in this study, however parental concerns about feeding differed.
      Further investigation is required to identify the drivers of parent concerns
      about feeding. Children displaying core risk factors warrant specific follow-up
      of feeding outcomes.

PMID- 30092235
TI  - Offspring of mothers with hyperglycaemia in pregnancy: The short term and long
      term impact. What is new?
AB  - The continuing rise in the global prevalence of diabetes and overweight or
      obesity has become a major burden for global health, as the pandemic is affecting
      both high and low-middle income countries (LMIC). At the same time, a similar
      pattern has been observed for all forms of hyperglycemia in pregnancy (HIP),
      diabetes during pregnancy and gestational diabetes. The offspring of mothers with
      HIP and/or overweight-obesity is receiving increasing attention as advances in
      early detection and treatment of HIP did not completely prevent macrosomia and
      its associated short-term perinatal disorders, whilst long term consequences are
      observed in the mother and in offspring as it reaches adulthood. This review
      discusses the current developments in the consequences of HIP in the offspring,
      with a particular focus on its long-term health at adulthood, and on
      intergenerational and transgenerational effects. HIP is emerging as one of the
      factors that can contribute, during the window of sensitivity to environmental
      cues constituted by the preconception, pregnancy, and early childhood, and as an
      amplifying factor linked to reproduction, to the current global epidemic of
      diabetes and non-communicable diseases (NCDs).

PMID- 30092234
TI  - Estimate of hepatocellular carcinoma incidence in patients with alcoholic
      cirrhosis.
AB  - BACKGROUND & AIMS: More than 90% of cases of hepatocellular carcinoma (HCC) occur
      in patients with cirrhosis, of which alcohol is a major cause. The CIRRAL cohort
      aimed to assess the burden of complications in patients with alcoholic cirrhosis,
      particularly the occurrence of HCC. METHODS: Patients with biopsy-proven
      compensated alcoholic cirrhosis were included then prospectively followed. The
      main endpoint was the incidence of HCC. Secondary outcomes were incidence of
      hepatic focal lesions, overall survival (OS), liver-related mortality and event
      free survival (EFS). RESULTS: From October 2010 to April 2016, 652 patients were
      included in 22 French and Belgian centers. During follow-up (median 29 months),
      HCC was diagnosed in 43 patients. With the limitation derived from the
      uncertainty of consecutive patients' inclusion and from a sizable proportion of
      dropouts (153/652), the incidence of HCC was 2.9 per 100 patient-years, and one-
      and two-year cumulative incidences of 1.8% and 5.2%, respectively. Although HCC
      fulfilled the Milan criteria in 33 cases (77%), only 24 patients (56%) underwent
      curative treatment. An explorative prognostic analysis showed that age, male
      gender, baseline alpha-fetoprotein, bilirubin and prothrombin were significantly
      associated with the risk of HCC occurrence. Among 73 deaths, 61 had a recorded
      cause and 27 were directly attributable to liver disease. At two years, OS, EFS
      and cumulative incidences of liver-related deaths were 93% (95% CI 90.5-95.4),
      80.3% (95% CI 76.9-83.9), and 3.2% (95% CI 1.6-4.8) respectively. CONCLUSION:
      This large prospective cohort incompletely representative of the whole population
      with alcoholic cirrhosis showed: a) an annual incidence of HCC of up to 2.9 per
      100 patient-years, suggesting that surveillance might be cost effective in these
      patients; b) a high proportion of HCC detected within the Milan criteria, but
      only one-half of detected HCC cases were referred for curative treatments; c) a
      two-year mortality rate of up to 7%. LAY SUMMARY: Cirrhosis is a risk factor for
      primary liver cancer, leading to recommendations for periodic screening. However,
      for alcohol-related liver disease the rational of periodic screening for
      hepatocellular carcinoma (HCC) is controversial, as registry and databased
      studies have suggested a low incidence of HCC in these patients and highly
      competitive mortality rates. In this study, a large cohort of patients with
      biopsy-proven alcoholic cirrhosis prospectively screened for HCC demonstrated a
      high annual incidence of HCC (2.9%) and a high percentage of small cancers
      theoretically eligible for curative treatment. This suggests that patients with
      liver disease related to alcohol should not be ruled out of screening.

PMID- 30092236
TI  - So-called "non-classic" ciliated Muconodular papillary tumors: a comprehensive
      comparison of the Clinicopathological and molecular features with classic
      ciliated Muconodular papillary tumors.
AB  - Ciliated muconodular papillary tumors (CMPTs) are characterized by tripartite
      cellular components of ciliated columnar cells, mucinous cells, and basal cells
      with predominantly papillary architecture. Some peripheral lung nodules may not
      demonstrate papillary architecture and tripartite cells that show bronchiolar
      differentiation; these nodules are termed "CMPTs with non-classic morphology" by
      some authors. To validate the rationality of "non-classic" CMPTs and to analyze
      the clinicopathological features of CMPTs, we enrolled 21 cases of lung nodules,
      comprising classic CMPTs (n=11) and so-called "non-classic" CMPTs (n=10). The
      status of driver mutations, including those in EGFR, BRAF, ALK, and KRAS, was
      examined by molecular tests. Clinical and radiological follow-up was performed (3
      27mo). Cilia as well as the mucinous and papillary components are usually present
      throughout classic CMPTs but may be absent in their "non-classic" counterparts.
      However, both entities present a bi-layer architecture with evidence of
      bronchiolar differentiation. Driver mutations involved the BRAF (n=6), EGFR (n=1)
      and ALK (n=1), were identified in 8 of 11 (73%) classic CMPTs, whereas driver
      mutations, comprising BRAF (n=2), EGFR (n=1),KRAS (n=1), were identified in 4 of
      10 (40%) "non-classic" lesions. Since it contains the largest series of Chinese
      patients with CMPTs, this study may expand the morphologic and molecular spectrum
      of CMPTs: a hallmark of CMPTs is bi-layer architecture with a continuous basal
      layer that can harbor high-frequency driver mutations. Recognition of the non
      classic morphology of CMPTs may be helpful to avoid misdiagnosis and unnecessary
      treatment.

PMID- 30092238
TI  - The effect of resin infiltration on proximal caries lesions in primary and
      permanent teeth. A systematic review and meta-analysis of clinical trials.
AB  - INTRODUCTION/OBJECTIVES: This systematic review aimed to critically appraise the
      evidence on resin infiltration for the clinical management of proximal caries
      lesions in primary and permanent teeth. DATA: Search terms included resin
      infiltration, micro-invasive and proximal caries. Potentially eligible studies
      involved proximal caries lesions treated with resin infiltration. Risk of bias
      assessment was performed using the Cochrane risk of bias tool and the quality of
      evidence was assessed with GRADE. SOURCES: Electronic Database search of
      published and unpublished literature was performed in April 22, 2018 within the
      following databases: MEDLINE via Pubmed, Cochrane Central Register of Controlled
      Trials, LILACS via BIREME, Open Grey, Clinical Trials.gov and National Research
      Register. STUDY SELECTION: Of 135 articles initially retrieved, 10 were eligible
      for inclusion in the systematic review comprising the results of 9 studies, while
      5 randomized controlled trials (RCTs) (6 articles) with unclear risk of bias
      contributed to the meta-analyses. Random effects meta-analyses were implemented
      and lesion progression treatment effects were estimated through Odds Ratios (ORs)
      along with associated 95% Confidence Intervals (95% CIs). CONCLUSIONS: Overall,
      there was strong evidence that proximal caries lesion progression was less likely
      to occur in permanent teeth following treatment with resin infiltration plus oral
      hygiene measures as compared to non- invasive methods (oral hygiene instructions)
      for follow up 18 months to 2 years (3 studies: OR = 0.14; 95% CI: 0.08, 0.25; P <
      0.001) as well as 3 years (4 studies: OR = 0.15; 95% CI: 0.06, 0.36; P < 0.001).
      The quality of the evidence was rated as moderate to low respectively.

PMID- 30092237
TI  - Unmarked genetic manipulation in Bacillus subtilis by natural co-transformation.
AB  - Bacillus subtilis is well known as both a model organism and as a microbial cell
      factory. Simple and scarless gene modification is a desirable tool for basic
      research and industrial applications of B. subtilis. It has been demonstrated
      that naturally competent strains of B. subtilis can uptake multiple different DNA
      molecules, a phenomenon called co-transformation. Here, we describe a co
      transformation-based method for generating unmarked mutants of B. subtilis. The
      PCR product containing the desired mutant allele is introduced into B. subtilis
      through co-transformation of the plasmid pUS20, which harbours a spectinomycin
      resistant marker (Spcr). The target mutation is acquired by screening
      transformants for integration of pUS20 by resistance to spectinomycin. Due to its
      unstable replication in B. subtilis, pUS20 is easily cured from transformants in
      the absence of spectinomycin. This method allows for point mutation delivery at
      frequencies of approximately 30%. Deletions and insertions of long DNA fragments
      can also be carried out efficiently using this method. Moreover, this method is
      also successful in Bacillus velezensis, indicating that it may be extended to
      other Bacillus species that can form natural competence.

PMID- 30092240
TI  - Towards response success prediction: An integrative approach using high
      resolution fMRI and autonomic indices.
AB  - Brainstem and midbrain nuclei are closely linked to effective cognitive
      performance and autonomic function. In the present study, we aimed to investigate
      indices of successful and unsuccessful response inhibition paying particular
      attention to the interplay between locus coeruleus (LC), ventral tegmental area
      (VTA)/substantia nigra (SN) and, most importantly, peripheral markers. We aimed
      to get insight in the predictive value of neural and physiological signals in
      response inhibition. A total of 35 healthy controls were recruited from the local
      community and a typical task of behavioral response inhibition (Go/No-Go
      paradigm) was applied. We used high-resolution fMRI, advanced brainstem analyses
      and specifically corrected for respiratory signal and cardiac noise. Our main
      results characterize specific neural activation patterns during successful and
      unsuccessful response inhibition especially comprising the anterior cingulate as
      well as the medial and lateral prefrontal cortex. A significant activation of the
      dopaminergic nuclei (VTA/SN) was found during error processing, but not during
      response inhibition. Most remarkably, specific neural activation patterns (i.e.,
      dorsal anterior cingulate cortex) as well as accompanying autonomic indices
      (i.e., skin conductance response (SCR)) were identified to hold predictive
      information on an individual's performance. In summary, the importance of the
      VTA/SN during error processing was shown. Furthermore, autonomic indices and
      specific neural activation patterns may contain valuable information to predict
      task performance.

PMID- 30092239
TI  - Relationship between Retinal Thickness Profiles and Visual Outcomes in Young
      Adults Born Extremely Preterm: The EPICure@19 Study.
AB  - PURPOSE: To quantify inner and outer retinal layer thicknesses and understand
      their relevance to visual function among young adults born extremely preterm
      (EP). DESIGN: Prospective observational study with 19 years of follow-up.
      PARTICIPANTS: A total of 354 eyes (226 eyes of former EP infants and 128 age
      matched full-term control eyes) from 177 young adults were evaluated. Among EP
      participants, 50% of eyes (112/226) were not previously diagnosed with neonatal
      retinopathy of prematurity (ROP), 38% of eyes (84) had ROP not deemed to require
      treatment in the neonatal period, and 13% of eyes (30) had neonatal cryotherapy
      or laser ablation for ROP. METHODS: Subjects underwent eye examinations including
      best-corrected visual acuity (BCVA) and Heidelberg Spectralis (Heidelberg
      Engineering, Heidelberg, Germany) macular spectral-domain (SD) OCT imaging.
      Retinal layers were auto-segmented and thickness profiles were computed at the
      fovea by the instrument software. MAIN OUTCOME MEASURES: Correlation between
      retinal sublayer thickness and BCVA. RESULTS: Compared with control eyes, the
      inner and outer retinal layers of EP eyes were significantly thicker and BCVA was
      significantly reduced. Retinal layer thicknesses and BCVA were similar for
      untreated EP eyes and those without neonatal ROP. In contrast, treated eyes had
      increased inner and outer retinal layer thickness and decreased vision. Inner
      retinal layer thickness was moderately correlated with worse BCVA (r = 0.30, P <
      0.001), but outer retinal layer thickness was not (r = -0.01, P = 0.80).
      Multivariate regression indicated ganglion cell layer thickness was a significant
      independent predictor of BCVA. CONCLUSIONS: Extremely premature birth influences
      maturation of the fovea and visual outcomes into early adult life. Increased
      ganglion cell layer thickness was associated with worse BCVA. Eyes requiring
      neonatal treatment for ROP had associated worse BCVA at the age of 19 years.

PMID- 30092241
TI  - Posttraumatic stress disorder with secondary psychotic features (PTSD-SP):
      Diagnostic and treatment challenges.
AB  - Trauma exposure leads to various psychiatric disorders including depression,
      anxiety, bipolar disorders, personality disorders, psychotic disorders, and
      trauma related disorders, especially posttraumatic stress disorder (PTSD). There
      are some overlapping symptoms of both PTSD and psychosis that make diagnosis
      challenging. Despite this overlap, the evidence of PTSD with comorbid psychosis
      as a distinct entity lies in the research showing biologic, genetic and treatment
      management differences between psychotic PTSD, non-psychotic PTSD, psychotic
      disorders and healthy controls. There is emerging evidence that PTSD with
      secondary psychotic features (PTSD-SP) might be a discrete entity of PTSD with
      known risk factors that increase its prevalence. This review has presented
      evidence for individuals with PTSD-SP being distinct in genetics and
      neurobiological factors. Individuals with PTSD and comorbid psychosis can benefit
      from evidence based psychotherapy (EBT). There is not enough evidence to
      recommend second generation antipsychotics (SGA) for PTSD-SP given that
      risperidone and quetiapine are the only SGAs studied in randomized controlled
      trials. Hence, developing an operational diagnostic criteria and treatment
      framework for clinical and research use is critical.

PMID- 30092242
TI  - Population Balance Model for Simulation of the Supersaturation-Precipitation
      Behavior of Drugs in Supersaturable Solid Forms.
AB  - We developed a simulation method to describe in vitro drug concentration-time
      profiles under supersaturated conditions. In a nonsink dissolution test of
      carbamazepine polymorphic form III (CBZIII), a model supersaturable solid, the
      concentration of carbamazepine reached a supersaturated state against its
      dihydrate form (CBZDH). After a certain period, de-supersaturation due to the
      precipitation of CBZDH was observed. In the simulation of this typical
      dissolution-precipitation profile, the precipitation process of CBZDH was
      simulated by a population balance model in which the rates of primary/secondary
      nucleation and growth of CBZDH were considered. Six rate constants in the
      precipitation model were determined from de-supersaturation profiles in unseeded
      isothermal crystallization experiments of CBZDH. The dissolution process of
      CBZIII was modeled on the basis of its dissolution profile under a sink
      condition. The simulated concentration versus time curves satisfactorily
      reproduced the characteristics of dissolution, supersaturation, and precipitation
      behavior of the model drug. The presented method will enable rational design of
      formulations and accurate prediction of the oral absorbability of drugs in
      supersaturable solid forms.

PMID- 30092244
TI  - Visual expertise for print in schizophrenia: Analysis of the N170 component.
AB  - Reading deficits have been reported for patients suffering from schizophrenia
      namely, specific phonological processing deficits. Phonological processing skills
      are crucial in the learning-to-read process as they are necessary to develop
      visual expertise for print, which reflects the neural specialization for print.
      The present study is the first to test visual expertise for print in patients
      suffering from schizophrenia by measuring the N170 component. Patients and pair
      matched healthy control participants performed a lexical decision task, in which
      words and symbols were presented. As expected, larger N170 amplitudes to word
      than to control stimuli were observed at the left occipito-temporal site PO7 but
      not at the PO8. More importantly, the modulation of the N170 as a function of the
      stimulus and hemisphere did not vary between patients and controls. This result
      suggests preserved visual expertise for print processing in patients suffering
      from schizophrenia.

PMID- 30092243
TI  - The influence of trait empathy on reactive aggression: An ERP study.
AB  - This study mainly investigated the electrophysiological mechanism underlying the
      effect of trait empathy on reactive aggression using event-related potentials
      (ERPs). Firstly, we computed the correlation between trait empathy and trait
      aggression in 413 male undergraduates. The trait empathy was positively
      correlated with trait aggression, whereas the perspective taking (cognitive
      empathy) and the empathic concern (affective empathy) dimensions of trait empathy
      were negatively correlated with physical aggression. Subsequently, we selected 50
      young male undergraduates respectively with high empathy (25) and low empathy
      (25) to complete a competitive reaction time task (a modified version of the
      Taylor Aggression Paradigm) against two mock opponents in high and low
      provocation conditions. The high empathy group selected lower average punishments
      against their opponents than the low empathy group. In the decision phase, high
      provocation elicited an enlarged ERP negativity compared to low provocation in
      the high empathy group. This observation was absent in the low empathy group. In
      the outcome phase, a feedback related negativity was observed in both groups. The
      low empathy group, but not the high empathy group, showed a significant average
      amplitude difference for losing and winning trials. The lack of a difference in
      ERP negativity amplitude in high empathy group suggests that punishing and being
      punished by opponents have a similar negative valence for this group.

PMID- 30092245
TI  - Regulation of P2X7 receptor function of neural progenitor cells in the
      hippocampal subgranular zone by neuronal activity in the dentate gyrus.
AB  - P2X7 receptors (Rs) mediate apoptosis/necrosis in neuronal and non-neuronal
      systems. Patch-clamp recordings from dentate gyrus (DG) granule cells in acutely
      prepared hippocampal slices of mice showed that incubation with 4-aminopyridine
      (4-AP) causes an excitability increase. This led to an enhanced sensitivity of
      P2X7Rs of the underlying subgranular zone neural progenitor cells (NPCs) towards
      dibenzoyl-ATP (Bz-ATP). The glutamatergic agonists NMDA and AMPA, as well as the
      purinergic agonist ATP also increased the Bz-ATP-induced current amplitudes
      (IBzATP). Tetrodotoxin as well as the standard antiepileptic drugs phenytoin,
      valproic acid and gabapentin counteracted the effect of 4-AP, most likely by
      decreasing the firing rate and/or action potential duration of DG granule cells
      and in consequence the release of ATP/glutamate onto NPCs. Experiments with
      organotypic hippocampal slice cultures confirmed these results also under
      conditions when 4-AP was applied for longer time periods and at much lower
      concentrations than used in acute slices. It was concluded that pathological
      firing modelled by 4-AP might trigger a sensitivity increase of P2X7Rs leading to
      necrosis/apoptosis of NPCs with the subsequent decrease of NPC, and in
      consequence, granule cell number. Hence, supersensitive P2X7Rs may exert a
      beneficial counter-regulatory effect by reducing the chances for the evolution of
      chronic temporal lobe epilepsy by ectopically located granule cells.

PMID- 30092246
TI  - A single cocaine administration alters dendritic spine morphology and impairs
      glutamate receptor synaptic retention in the medial prefrontal cortex of
      adolescent rats.
AB  - The brain is still maturing during adolescence and interfering with such a
      vulnerable period may lead to structural and functional consequences. We
      investigated the effect of a single cocaine exposure on dendritic spine structure
      and glutamate dynamics in the medial prefrontal cortex (mPFC) of adolescent rats
      7 days after a single cocaine administration. We found a reduced number of
      dendritic spines, suggesting that cocaine lowers the density of dendritic spines
      in the mPFC of adolescent rats. Since dendritic spines are postsynaptic
      glutamatergic protrusions, we investigated the main determinants of glutamate
      postsynaptic responsiveness. In the postsynaptic density, cocaine reduced the
      expression of the NMDA receptor subunits GluN1, GluN2A and GluN2B as well as of
      the AMPA GluA1 and GluA2 subunits. Cocaine also impaired their synaptic stability
      since the expression of the scaffolding proteins SAP102 and SAP97, critical for
      the anchoring of such receptors at the postsynaptic membrane, was reduced as
      well. The expression of PSD-95 and Arc/Arg3.1, which play structural and
      functional roles in glutamate neurons, was also similarly reduced. Such changes
      were not found in the whole homogenate, ruling out a translational effect of
      cocaine and implying, rather, an impaired synaptic retention at the active zones
      of the synapse. Notably, neither these critical glutamate determinants nor the
      density and morphology of the dendritic spines were altered in the mPFC of adult
      animals, suggesting that a single cocaine exposure selectively impairs the
      developmental trajectory of the glutamate synapse. These results indicate a
      dynamic impairment of mPFC glutamate homeostasis during a critical developmental
      window that persists for at least one week after a single cocaine administration.
      Our results identify dysfunctional glutamate synapse as a major contributor to
      the mechanisms that distinguish adolescent vs. adult outcomes of a single cocaine
      exposure.

PMID- 30092247
TI  - Early detection of diabetic retinopathy with flicker electroretinography,
      proteomics, and oximetry.

PMID- 30092248
TI  - N-terminal phosphorylation of glutaminase C decreases its enzymatic activity and
      cancer cell migration.
AB  - The mitochondrial phosphate-activated glutaminase C (GAC) is produced by the
      alternative splicing of the GLS gene. Compared to the other GLS isoform, the
      kidney-type glutaminase (KGA), GAC is more enzymatically efficient and of
      particular importance for cancer cell growth. Although its catalytic mechanism is
      well understood, little is known about how post-translational modifications can
      impact GAC function. Here, we identified by mass spectrometry a phosphorylated
      serine at the GLS N-terminal domain (at position 95) and investigated its role on
      regulating GAC activity. The ectopic expression of the phosphomimetic mutant
      (GAC.S95D) in breast cancer cells, compared to wild-type GAC (GAC.WT), led to
      decreased glutaminase activity, glutamine uptake, glutamate release and
      intracellular glutamate levels, without changing GAC sub-cellular localization.
      Interestingly, cells expressing the GAC.S95D mutant, compared to GAC.WT,
      presented decreased migration and vimentin level, an epithelial-to-mesenchymal
      transition marker. These results reveal that GAC is post-translationally
      regulated by phosphorylation, which affects cellular glutamine metabolism and
      glutaminase-related cell phenotype.

PMID- 30092250
TI  - New Bis copper complex ((Z) -4 - ((4-chlorophenyl) amino) -4-oxobut-2-enoyl)
      oxy): Cytotoxicity in 4T1 cells and their toxicogenic potential in Swiss mice.
AB  - Copper (II) complexes are promising in the development of new synthetic models
      for cancer treatment. In this context, we synthesized a new copper complex
      containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4
      chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its
      antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their
      toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and
      genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by
      the increase in ATM and p21 expression, it induced the cells to apoptosis by
      increasing BAX and caspase-7. In vivo the compound was genotoxic in mice but did
      not show permanent damage, observed by the absence of increased micronucleus
      frequency, and did not induce changes in the biometric parameters of the animals.
      These results indicate that the new copper complex, described firstly in this
      work, presents therapeutic potential for breast cancer.

PMID- 30092249
TI  - Hippo/YAP signaling pathway mitigates blood-brain barrier disruption after
      cerebral ischemia/reperfusion injury.
AB  - Ischemia/reperfusion (I/R) injuries commonly lead to breakdown of the blood-brain
      barrier (BBB). Restoration of the BBB can relieve neurologic damage caused by I/R
      injuries. The Hippo/YAP signaling pathway mediates cell proliferation, regulated
      cell death, and differentiation in various organisms and has been shown to
      participate in the restoration of the heart after I/R. In this study, we
      investigated whether the Hippo/YAP pathway plays a role in I/R injury in brain,
      especially in regard to I/R-induced BBB breakdown. The results of our study
      indicate that I/R injury led to an overall decrease in activity of the core
      proteins, YAP and TAZ, over a 24-h period. The most dramatic change was observed
      1.5 h after reperfusion. In rats that underwent 1.5 h of reperfusion,
      intraperitoneal injection of YAP agonist dexamethasone activated YAP and TAZ and
      led to improved neurologic function, smaller brain infarct sizes, increased
      levels of tight junction proteins, decreased BBB permeability, decreased cerebral
      edema, and less apoptosis. Our results suggest that YAP exerts neuroprotective
      effects on the damaged brain that are likely related to restoration of the BBB.

PMID- 30092251
TI  - Inhibition of influenza A virus by mixed siRNAs, targeting the PA, NP, and NS
      genes, delivered by hybrid microcarriers.
AB  - In the present study, a highly effective carrier system has been developed for
      the delivery of antiviral siRNA mixtures. The developed hybrid microcarriers,
      made of biodegradable polymers and SiO2 nanostructures, more efficiently mediate
      cellular uptake of siRNA than commercially available liposome-based reagents and
      polyethyleneimine (PEI); they also demonstrate low in vitro toxicity and
      protection of siRNA from RNase degradation. A series of siRNA designs (targeting
      the most conserved regions of three influenza A virus (IAV) genes: NP, NS, and
      PA) were screened in vitro using RT-qPCR, ELISA analysis, and hemagglutination
      assay. Based on the results of screening, the three most effective siRNAs (PA
      1630, NP-717, and NS-777) were selected for in situ encapsulation into hybrid
      microcarriers. It was revealed that pre-treatment of cells with a mixture of PA
      1630, NP-717, and NS-777 siRNAs, delivered by hybrid microcarriers, provided
      stronger inhibition of viral M1 mRNA expression and control of NP protein level,
      after viral infection, than single pre-treatment by any of three encapsulated
      siRNAs used in the study. Moreover, the effective inhibition of replication in
      several IAV subtypes (H1N1, H1N1pdm, H5N2, and H7N9) using a cocktail of the
      three selected siRNAs, delivered by our hybrid capsules to the cells, was
      achieved. In conclusion, we have developed a proof-of-principle which shows that
      our hybrid microcarrier technology (utilizing a therapeutic siRNA cocktail) may
      represent a promising approach in anti-influenza therapy.

PMID- 30092252
TI  - Rapid and efficient in vitro excision of BAC sequences from herpesvirus genomes
      using Cre-mediated recombination.
AB  - Cre-mediated recombination is a widely used technique for the re-arrangement of
      DNA sequences that are bracketed by loxP recognition sites. This bacteriophage P1
      enzyme is commonly used to excise the bacterial artificial chromosome (BAC)
      sequence, a vector sequence used for large herpesvirus genomes for the purposes
      of propagation and manipulation in Escherichia coli. Most methods utilize cell
      lines that can be induced for the expression of Cre enzyme to facilitate this
      excision. In addition, methods have been developed that express Cre from the
      virus genome and enable auto-excision of the BAC plasmid. We report a versatile
      and rapid in vitro method based on purified Cre enzyme to carry out the same
      process in a test tube and does not require cell line generation or cloning into
      the virus genome. This method greatly increases the repertoire of methods
      available to modify the genome prior to reconstitution of virus infectivity in a
      mammalian host.

PMID- 30092253
TI  - Biochemical and Structural Insights into an Fe(II)/alpha-Ketoglutarate/O2
      Dependent Dioxygenase, Kdo 3-Hydroxylase (KdoO).
AB  - During lipopolysaccharide biosynthesis in several pathogens, including
      Burkholderia and Yersinia, 3-deoxy-d-manno-oct-2-ulosonic acid (Kdo) 3
      hydroxylase, otherwise referred to as KdoO, converts Kdo to d-glycero-d-talo-oct
      2-ulosonic acid (Ko) in an Fe(II)/alpha-ketoglutarate (alpha-KG)/O2-dependent
      manner. This conversion renders the bacterial outer membrane more stable and
      resistant to stresses such as an acidic environment. KdoO is a membrane
      associated, deoxy-sugar hydroxylase that does not show significant sequence
      identity with any known enzymes, and its structural information has not been
      previously reported. Here, we report the biochemical and structural
      characterization of KdoO, Minf_1012 (KdoMI), from Methylacidiphilum infernorum
      V4. The de novo structure of KdoMI apoprotein indicates that KdoOMI consists of
      13 alpha helices and 11 beta strands, and has the jelly roll fold containing a
      metal binding motif, HXDX111H. Structures of KdoMI bound to Co(II), KdoMI bound
      to alpha-KG and Fe(III), and KdoMI bound to succinate and Fe(III), in addition to
      mutagenesis analysis, indicate that His146, His260, and Asp148 play critical
      roles in Fe(II) binding, while Arg127, Arg162, Arg174, and Trp176 stabilize alpha
      KG. It was also observed that His225 is adjacent to the active site and plays an
      important role in the catalysis of KdoOMI without affecting substrate binding,
      possibly being involved in oxygen activation. The crystal structure of KdoOMI is
      the first completed structure of a deoxy-sugar hydroxylase, and the data
      presented here have provided mechanistic insights into deoxy-sugar hydroxylase,
      KdoO, and lipopolysaccharide biosynthesis.

PMID- 30092255
TI  - Some chinks in RAS armor.

PMID- 30092254
TI  - Transcutaneously refillable nanofluidic implant achieves sustained level of
      tenofovir diphosphate for HIV pre-exposure prophylaxis.
AB  - Pre-exposure prophylaxis (PrEP) with antiretroviral (ARV) drugs are effective at
      preventing human immunodeficiency virus (HIV) transmission. However,
      implementation of PrEP presents significant challenges due to poor user
      adherence, low accessibility to ARVs and multiple routes of HIV exposure. To
      address these challenges, we developed the nanochannel delivery implant (NDI), a
      subcutaneously implantable device for sustained and constant delivery of
      tenofovir alafenamide (TAF) and emtricitabine (FTC) for HIV PrEP. Unlike existing
      drug delivery platforms with finite depots, the NDI incorporates ports allowing
      for transcutaneous refilling upon drug exhaustion. NDI-mediated drug delivery in
      rhesus macaques resulted in sustained release of both TAF and FTC for 83 days, as
      indicated by concentrations of TAF, FTC and their respectively metabolites in
      plasma, PBMCs, rectal mononuclear cells and tissues associated with HIV
      transmission. Notably, clinically relevant preventative levels of tenofovir
      diphosphate were achieved as early as 3 days after NDI implantation. We also
      demonstrated the feasibility of transcutaneous drug refilling to extend the
      duration of PrEP drug delivery in NHPs. Overall, the NDI represents an innovative
      strategy for long-term HIV PrEP administration in both developed and developing
      countries.

PMID- 30092256
TI  - Identification and characterization of a novel PRR of fibrinogen-related protein
      in Apostichopus japonicus.
AB  - Fibrinogen-related proteins (FREPs) play important roles in innate immunity by
      recognizing pathogen associated molecular patterns on pathogenic bacteria
      surfaces via conserved fibrinogen-like domain (FBG). In this paper, the full
      length cDNA of Apostichopus japonicus FREP (designated as AjFREP) was cloned
      combined with rapid amplification of cDNA ends (RACE) and transcriptome
      sequencing. The full-length cDNA of AjFREP was of 2110 bp with an open reading
      frame (ORF) of 1659 bp. SMART analysis revealed that the AjFREP contained a
      typical signal peptide of 19 amino acid residues, a FBG and two unusual epidermal
      growth factor-like domains (EGFs). Multiple sequence alignments suggested that
      FBG domain shared a remarkably high structural conservation in polypeptide
      binding site and Ca2+ binding site. Tissue distribution analysis revealed that
      AjFREP was constitutively expressed in all examined tissues with the largest
      magnitude in coelomocytes, indicating AjFREP might play an important role in
      immune defense. The mRNA level of AjFREP in coelomocytes was sharply up-regulated
      by Vibrio splendidus challenge, and reached its peak expression at 48 h. Knock
      down AjFREP by specific siRNA could significantly repress the coelomocyte
      phagocytosis rate. Meantime, the survival number of V. splendidus in the coelomic
      fluid was promoted. All these current results indicated that AjFREP might be
      involved in pathogen clearance through mediating coelomocytes phagocytosis
      activity.

PMID- 30092257
TI  - Adjuvant efficacy of G2 (buffalo spleen extraction) against Yersinia septicemia
      in rainbow trout (Onchorhynchus mykiss).
AB  - Adjuvant effect of G2 (extraction of buffalo spleen) was assessed in
      intraperitoneally immunized rainbow trout (100-150 g) with killed- Y. ruckeri
      bacterin biotype I [0.1 mL (1 * 107 cells/fish) of vaccine diluted with the
      adjuvant in a ratio of 1:1 (V/V)] at 12.4 +/- 1.3  degrees C for 10 weeks.
      Leukocyte and lymphocyte counts, anti-Y. ruckeri antibody titer and relative
      percent survival (RPS) in fish vaccinated with vaccine containing the adjuvant
      were significantly higher than the immunized fish with Y. ruckeri antigen alone
      throughout the experiment (P < 0.05), but neutrophils count and lysozyme activity
      were mostly significantly higher in the latter group (P < 0.05). No difference
      was seen in the complement activity between vaccinated fish containing the
      adjuvant and vaccine alone (P > 0.05). The results of this work for the first
      time demonstrated that inclusion of G2 as an adjuvant in Y. urckeri vaccine can
      improve the efficacy of the vaccine against Yersinia septicemia in rainbow trout.

PMID- 30092258
TI  - MAOA genotype modulates default mode network deactivation during inhibitory
      control.
AB  - It has been demonstrated, in a long line of research, that the low-activity
      genotype of the monoamine oxidase A (MAOA) gene is associated with aggression.
      Previous work has linked impaired response inhibition to aggression, but little
      is known about how this relates to the purported MAOA-aggression relationship in
      adolescents. Here, we examined how MAOA genotype influences neural correlates of
      inhibitory control in 74 healthy male adolescents using a GoStop and a Go/Nogo
      task while differentiating between action cancelation and action restraint.
      Carriers of the low-expressing MAOA alleles (MAOA-L) did not show altered brain
      activation in the prefrontal-subcortical inhibition network relative to carriers
      of the high-expressing alleles across inhibition conditions. However, they
      exhibited a more pronounced deactivation during response inhibition in the
      posterior cingulate cortex (PCC) and precuneus, areas belonging to the default
      mode network (DMN). Larger DMN suppression in MAOA-L carriers might represent a
      compensation mechanism for impaired cognitive control.

PMID- 30092259
TI  - The impact of SNAP25 on brain functional connectivity density and working memory
      in ADHD.
AB  - Attention deficit/hyperactivity disorder (ADHD) is a highly heritable
      neurodevelopment disorder. The deficit in working memory is a central cognitive
      impairment in ADHD. The SNAP-25 is a neurotransmitter vesicular docking protein
      whose MnlI polymorphism (rs3746544) is located in the 3'-untranslated region (3'
      UTR) and known to be linked to ADHD, but the underlying mechanism of this
      polymorphism remains unclear. Using a functional connectivity density (FCD)
      mapping method based on resting-state functional magnetic resonance imaging in a
      sample of male children diagnosed with ADHD, we first investigated the
      correlation between SNAP-25 rs3746544 and FCD hubs. Compared with rs3746544 G
      allele carriers, TT homozygous, which confers a high risk for ADHD, exhibited
      significantly decreased local and long-range FCD in anterior cingulate cortex,
      and decreased local FCD in the dorsal lateral prefrontal cortex. Moreover, both
      higher local and long-range FCD could predict better WM capacity. The current
      findings provide new insights into the underlying neural mechanisms linking SNAP
      25 rs3746544 with the risk for ADHD via the endophenotype of brain functional
      connectivity.

PMID- 30092260
TI  - Nanoparticles and their antimicrobial properties against pathogens including
      bacteria, fungi, parasites and viruses.
AB  - In recent year, propagation and resistance of pathogenic microorganisms
      (bacteria, fungi and virals) to common antimicrobial agents has led to serious
      health and food problems. Today, nanotechnology science and nanoparticles (NPs)
      have been identified as a new approach to deal with this problem because of their
      inherent antimicrobial activity. Several studies have reported that, NPs (metal
      and metal oxide) are considered as a group of materials that can be studied due
      to their antimicrobial properties. In this review, we investigated recent studies
      regarding the antimicrobial activity of NPs with their mechanism of action. Many
      research has proved that particle size is a significant factor which indicates
      the antimicrobial effectiveness of NPs. The use of NPs as antimicrobial component
      especially in the food additives and medical application can be one of the new
      and considerable strategies for overcoming pathogenic microorganisms.
      Nevertheless, more studies must be conducted to minimize the possible toxicity of
      NPs in order to use as suitable alternatives for disinfectants and antibacterial
      agents in food applications.

PMID- 30092261
TI  - Virulence factors and determination of antifungal susceptibilities of Candida
      species isolated from palm wine and sorghum beer.
AB  - Since it has been considered that Candida species in food or drinks may,
      following ingestion, enter the bloodstream and cause fungaemia, the presence of
      these yeast species in traditional alcoholic beverages may be of some clinical
      significance. Thus we attempted to assess virulence factors and antifungal
      susceptibility profile of Candida strains and other potential pathogenic yeasts
      isolated from palm wine and sorghum beer (tchapalo). Of the 23 yeast isolates
      from palm wine, phospholipase, esterase and haemolysin production was revealed
      amongst 69.6%, 65.2% and 100% isolates respectively with high activity belonging
      to Candida tropicalis strains. All the isolates were biofilm producers at
      variable degree but none showed proteinase activity. When the isolates were
      tested for their susceptibility to five antifungal agents, we found that
      ketoconazole (91.3%) followed by fluconazole (78.3%) and amphotericin B (73.9%)
      were the most potent agents. Of the 14 isolates from tchapalo, 57.1%, 87.5% and
      57.1% exhibited phospholipase, haemolysin and esterase activity respectively.
      They did not also show proteinase activity while 87.5% produced biofilm. The
      majority of the isolates were susceptible to azoles (92.7%) and amphotericin B
      (85.3%) but they were 5-flucytosine resistant like palm wine strains.

PMID- 30092262
TI  - Pain severity as a mediator of the association between depressive symptoms and
      physical performance in knee osteoarthritis.
AB  - OBJECTIVE: Depressive symptoms in knee osteoarthritis (OA) are associated with
      increased pain severity and declines in physical performance. This study examined
      whether pain severity mediates the association between depressive symptoms and
      physical performance in persons with radiographic knee OA. METHOD: Three years of
      annual data from participants (n = 1,463) with radiographic knee OA in the
      Osteoarthritis Initiative (OAI) were analyzed. Depressive symptoms were measured
      using the Center for Epidemiological Studies Depression (CES-D) scale. Pain
      severity was evaluated with the Western Ontario and McMaster Universities
      Arthritis Index. Physical performance was assessed via standardized gait speed.
      Marginal structural models were used to assess the direct (unmediated) effects of
      depressive symptoms on physical performance and indirect (mediated) effects
      through pain severity. RESULTS: Direct and indirect effects for a difference in
      CES-D score of 0-1 were -0.0051 (95% confidence intervals (CI): -0.0053, -0.0049)
      and -0.0016 (95% CI: -0.0024, -0.0007) standard deviations in gait speed,
      respectively. Higher depressive symptom severity exhibited diminishing,
      incremental, direct and indirect effects and for a difference in CES-D score of
      15-16 were -0.0045 (95% CI: -0.0047, -0.0042) and -0.0009 (95% CI: -0.0014, 
      0.0004) standard deviations in gait speed, respectively. Therefore, the magnitude
      of the mediated, indirect effect, was never larger than 24%. CONCLUSION: Pain
      severity mediated approximately one-fifth of the association between depressive
      symptoms and physical performance in persons with radiographic knee OA, and the
      diminishing incremental effects may explain why unimodal treatment strategies
      with a single disease target are often ineffective in depressed OA patients.

PMID- 30092264
TI  - Ocular and systemic manifestations of beta-propeller protein-associated
      neurodegeneration.
AB  - Beta-propeller protein-associated neurodegeneration (BPAN) is a rare genetic
      disorder characterized by neurodegeneration with brain iron accumulation (NBIA).
      We report an infant diagnosed with BPAN who was found to have high myopia and
      astigmatism, strabismus, and bilateral retinal pigmentary changes. While retinal
      pigmentary changes have been described in other disorders of NBIA, it has been
      only rarely reported in BPAN.

PMID- 30092265
TI  - Who needs penicillin allergy testing?

PMID- 30092263
TI  - Cost-effectiveness of health coaching and financial incentives to promote
      physical activity after total knee replacement.
AB  - OBJECTIVE: We evaluated the cost-effectiveness of Telephonic Health Coaching and
      Financial Incentives (THC + FI) to promote physical activity in total knee
      replacement recipients. DESIGN: We used the Osteoarthritis Policy Model, a
      computer simulation of knee osteoarthritis, to evaluate the cost-effectiveness of
      THC + FI compared to usual care. We derived transition probabilities, utilities,
      and costs from trial data. We conducted lifetime analyses from the healthcare
      perspective and discounted all cost-effectiveness outcomes by 3% annually. The
      primary outcome was the Incremental Cost-Effectiveness Ratio (ICER), defined as
      the ratio of the differences in costs and Quality-Adjusted Life Years (QALYs)
      between strategies. We considered ICERs <$100,000/QALY to be cost-effective. We
      conducted one-way sensitivity analyses that varied parameters across their 95%
      confidence intervals (CI) and limited the efficacy of THC + FI to 1 year or to 9
      months. We also conducted a probabilistic sensitivity analysis (PSA),
      simultaneously varying cost, utilities, and transition probabilities. RESULTS:
      THC + FI had an ICER of $57,200/QALY in the base case and an ICER below
      $100,000/QALY in most deterministic sensitivity analyses. THC + FI cost
      effectiveness depended on assumptions about long-term efficacy; when efficacy was
      limited to 1 year or to 9 months, the ICER was $93,300/QALY or $121,800/QALY,
      respectively. In the PSA, THC + FI had an ICER below $100,000/QALY in 70% of
      iterations. CONCLUSIONS: Based on currently available information, THC + FI might
      be a cost-effective alternative to usual care. However, the uncertainty
      surrounding this choice is considerable, and further research to reduce this
      uncertainty may be economically justified.

PMID- 30092266
TI  - Association of atopic dermatitis with allergic, autoimmune, and cardiovascular
      comorbidities in US adults.
AB  - BACKGROUND: Atopic dermatitis (AD) has been associated with multiple comorbid
      extracutaneous and systemic disorders. The relation between AD severity and
      disease comorbidities is complex and not fully understood. OBJECTIVE: To
      determine the complex relation between AD severity and comorbidities. METHODS: A
      cross-sectional US population-based study of 8,217 adults who were participants
      in a nationally representative internet health panel was performed using a
      structured questionnaire. A diagnosis of AD was determined using modified United
      Kingdom Working Party Criteria for AD (n = 602). AD severity was assessed using
      Patient-Oriented Scoring AD, Patient-Oriented Eczema Measure, Dermatology Life
      Quality Index, and self-reported global AD severity. Logistic regression and
      structural equation models were used to explore associations of AD with self
      reported allergic, cardiometabolic, anxiety and depression, and autoimmune
      disease. RESULTS: In multivariable regression models controlling for
      sociodemographics, AD was associated with higher odds of asthma (adjusted odds
      ratio [OR] 2.09, 95% confidence interval [CI] 1.71-2.55), hay fever (OR 4.31, 95%
      CI 3.27-5.69), food allergy (OR 2.07, 95% CI 1.54-2.77), anxiety and depression
      (OR 2.34, 95% CI 1.91-2.87), autoimmune disease (OR 3.05, 95% CI 2.31-4.03),
      obesity (OR 1.37, 95% CI 1.13-1.67), diabetes (OR 1.52, 95% CI 1.16-1.99), high
      blood pressure (OR 1.46, 95% CI 1.18-1.80), and heart disease (OR 1.94, 95% CI
      1.40-2.70) compared with controls (P < .01 for all). All these associations were
      significant in mild and/or moderate disease, with even stronger effects in severe
      AD. Results of structural equation models showed direct effects of moderate to
      severe AD on food allergy, anxiety and depression, and diabetes, direct and
      indirect effects on obesity, and indirect effects on high blood pressure and
      heart disease. CONCLUSION: There is a strong relation of AD severity to allergic,
      autoimmune, and cardiovascular comorbidities.

PMID- 30092267
TI  - Content and construct validity, predictors, and distribution of self-reported
      atopic dermatitis severity in US adults.
AB  - BACKGROUND: Atopic dermatitis (AD) is associated with skin lesions, multiple
      symptoms, and effect of quality of life, all of which factor into disease
      severity. Self-reported global AD severity may be a valid severity assessment for
      epidemiologic research. OBJECTIVE: To validate self-reported global AD severity
      in a representative cohort of adults with AD. METHODS: Preliminary probing
      cognitive interviews were performed (n = 8). Next, a cross-sectional US
      population-based survey study of adults with AD was performed. AD was diagnosed
      using an adap/tation of the UK Working Party criteria (n = 602). AD severity was
      assessed using self-reported global AD severity (mild, moderate, severe), Patient
      Oriented Scoring AD (PO-SCORAD), Patient-Oriented Eczema Measure (POEM), Numeric
      Rating Scale (NRS)-itch, NRS-sleep, NRS-pain, and Hospital Anxiety and Depression
      Scale (HADS). RESULTS: Self-reported global AD severity had good content
      validity. Self-reported global AD severity had strong correlations with PO-SCORAD
      (Spearman correlation rho = 0.61) and objective PO-SCORAD (rho = 0.61); moderate
      correlations with POEM (rho = 0.54), NRS-itch (rho = 0.44), NRS-pain (rho =
      0.46), and HADS (rho = 0.41); and weak correlation with NRS-sleep (rho = .32) (P
      < .001 for all). Consistent and significant correlations were observed in
      stratified analyses by age, sex, race/ethnicity, and level of education. There
      were stepwise increases of PO-SCORAD, NRS-itch, NRS-sleep, NRS-pain, POEM, and
      HADS with increasing self-reported global AD severity (Kruskal-Wallis test, P <
      .01). There was weak-moderate concordance between self-reported AD severity and
      established severity strata for PO-SCORAD (rho = 0.44), NRS-itch (rho = 0.30),
      and POEM (rho = 0.43). Rather, self-reported global AD severity was best
      predicted by a combination of PO-SCORAD, POEM, NRS-itch, NRS-pain, and HADS. No
      differential item reporting was found by age, sex, or race/ethnicity. CONCLUSION:
      Self-reported AD severity simultaneously assesses multiple AD constructs and
      appears to be sufficiently valid for assessing AD severity in clinical and
      epidemiologic studies.

PMID- 30092268
TI  - Regenerating islet-derived 1alpha (REG-1alpha) protein increases tau
      phosphorylation in cell and animal models of tauopathies.
AB  - REG-1alpha, a secreted protein containing a C-type lectin domain, is expressed in
      various organs and plays different roles in digestive system cells in
      physiological and pathological conditions. Like other members of the Reg family,
      REG-1alpha is expressed also in the brain where it has different functions. For
      instance, we previously reported that REG-1alpha regulates neurite outgrowth and
      is overexpressed during the very early stages of Alzheimer's disease (AD).
      However, REG-1alpha function in neural cells during neural degeneration remains
      unknown. First, REG-1alpha and phosphorylated tau expression were assessed in
      tissue sections from the hippocampus, representing neurofibrillary tangles
      (NFTs), from patients with AD, and from basal ganglia, representing subcortical
      NFTs, from patients with progressive supranuclear palsy (PSP). We found an
      association between REG-1alpha expression, tau hyperphosphorylation and NFTs in
      human brain samples from patients with these neurodegenerative diseases. Then,
      the effects of REG-1alpha overexpression on tau phosphorylation and axonal
      morphology were investigated i) in primary cultures of rat neurons that express
      human tau P301L and ii) in a transgenic zebrafish model of tauopathy that
      expresses human tau P301L. In the tau P301L cell model, REG-1alpha overexpression
      increased tau phosphorylation at the S202/T205 and S396 residues (early and late
      stages of abnormal phosphorylation, respectively) through the AKT/GSK3-beta
      pathway. This effect was associated with axonal defects both in tau P301L
      expressing rat neurons and zebrafish embryos. Our findings suggest a functional
      role for REG-1alpha during tauopathy development and progression and,
      specifically, its involvement in the modification of tau phosphorylation temporal
      sequence.

PMID- 30092271
TI  - Effective inhibition of rifampicin-resistant Chlamydia trachomatis by the novel
      DNA-dependent RNA polymerase inhibitor corallopyronin A.

PMID- 30092270
TI  - Alpha-synuclein deregulates the expression of COL4A2 and impairs ER-Golgi
      function.
AB  - Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy
      neurites, the typical pathological hallmarks in Parkinson's disease (PD) and
      Dementia with Lewy bodies. aSyn is capable of inducing transcriptional
      deregulation, but the precise effect of specific aSyn mutants associated with
      familial forms of PD, remains unclear. Here, we used transgenic mice
      overexpressing human wild-type (WT) or A30P aSyn to compare the transcriptional
      profiles of the two animal models. We found that A30P aSyn promotes strong
      transcriptional deregulation and increases DNA binding. Interestingly, COL4A2, a
      major component of basement membranes, was found to be upregulated in both A30P
      aSyn transgenic mice and in dopaminergic neurons expressing A30P aSyn, suggesting
      a crucial role for collagen related genes in aSyn-induced toxicity. Finally, we
      observed that A30P aSyn alters Golgi morphology and increases the susceptibility
      to endoplasmic reticulum (ER) stress in dopaminergic cells. In total, our
      findings provide novel insight into the putative role of aSyn on transcription
      and on the molecular mechanisms involved, thereby opening novel avenues for
      future therapeutic interventions in PD and other synucleinopathies.

PMID- 30092269
TI  - Loss of MICOS complex integrity and mitochondrial damage, but not TDP-43
      mitochondrial localisation, are likely associated with severity of CHCHD10
      related diseases.
AB  - Following the involvement of CHCHD10 in FrontoTemporal-Dementia-Amyotrophic
      Lateral Sclerosis (FTD-ALS) clinical spectrum, a founder mutation (p.Gly66Val) in
      the same gene was identified in Finnish families with late-onset spinal motor
      neuronopathy (SMAJ). SMAJ is a slowly progressive form of spinal muscular atrophy
      with a life expectancy within normal range. In order to understand why the
      p.Ser59Leu mutation, responsible for severe FTD-ALS, and the p.Gly66Val mutation
      could lead to different levels of severity, we compared their effects in patient
      cells. Unlike affected individuals bearing the p.Ser59Leu mutation, patients
      presenting with SMAJ phenotype have neither mitochondrial myopathy nor mtDNA
      instability. The expression of CHCHD10S59L mutant allele leads to disassembly of
      mitochondrial contact site and cristae organizing system (MICOS) with
      mitochondrial dysfunction and loss of cristae in patient fibroblasts. We also
      show that G66V fibroblasts do not display the loss of MICOS complex integrity and
      mitochondrial damage found in S59L cells. However, S59L and G66V fibroblasts show
      comparable accumulation of phosphorylated mitochondrial TDP-43 suggesting that
      the severity of phenotype and mitochondrial damage do not depend on mitochondrial
      TDP-43 localization. The expression of the CHCHD10G66V allele is responsible for
      mitochondrial network fragmentation and decreased sensitivity towards apoptotic
      stimuli, but with a less severe effect than that found in cells expressing the
      CHCHD10S59L allele. Taken together, our data show that cellular phenotypes
      associated with p.Ser59Leu and p.Gly66Val mutations in CHCHD10 are different;
      loss of MICOS complex integrity and mitochondrial dysfunction, but not TDP-43
      mitochondrial localization, being likely essential to develop a severe motor
      neuron disease.

PMID- 30092272
TI  - Successful management with fosfomycin + ceftazidime of an infection caused by
      multiple highly-related subtypes of multidrug-resistant and extensively drug
      resistant KPC-producing Serratia marcescens.

PMID- 30092273
TI  - The role of nutraceuticals in the treatment of primary dyslipidemia.

PMID- 30092274
TI  - Infective endocarditis due to Enterococcus faecalis manifesting as pemphigus
      foliaceus.

PMID- 30092275
TI  - Laser-assisted orbital or rotational atherectomy: a hybrid treatment strategy for
      balloon-uncrossable lesions.

PMID- 30092276
TI  - Migratory and resident waders differ in risk taking on the wintering grounds.
AB  - Animals, including birds, have to optimize their escape strategies under the risk
      of predation. Level of risk-taking is often estimated as flight initiation
      distance (FID), which is assumed to reflect the trade-off between costs of escape
      and benefits of staying put. Despite costs and benefits of escape may change
      during the season, previous studies have focused mainly on breeding bird
      populations. Here, we focused on risk taking in migratory and resident
      populations of waders (Charadriiformes) at the wintering grounds in tropical
      Africa. Phylogenetically informed comparative analyses revealed significant
      correlation between starting distance, body mass and, marginally, reproductive
      effort and FID, but no correlation between flock size and FID in wintering
      waders. Interestingly, despite no differences in body mass, reproductive effort
      and flock size, FID significantly differed between migratory and resident wader
      species after controlling for the potential effect of confounding variables, with
      FID being shorter in resident species. This suggests that such differences in
      risk perception are linked to some other factors as, for instance, the level of
      familiarity of waders with local environments at their wintering grounds and
      previous experience with humans. Our results may have also implications for avian
      conservation of migratory species at wintering grounds.

PMID- 30092277
TI  - Effect of compression waveform and resuscitation duration on blood flow and
      pressure in swine: One waveform does not optimally serve.
AB  - BACKGROUND: Chest compression (CC) research primarily focuses on finding the
      'optimum' compression waveform using a variety of compression efficacy metrics.
      Blood flow is rarely measured systematically with high fidelity. Using a
      programmable mechanical chest compression device, we studied the effect of inter
      compression pauses in a swine model of cardiac arrest, testing the hypothesis
      that a single 'optimal' CC waveform exists based on measurements of resulting
      blood flow. METHODS: Hemodynamics were studied in 9 domestic swine (~30 kg) using
      multiple flow probes and standard physiological monitoring. After 10 min of
      ventricular fibrillation, five mechanical chest compression waveforms (5.1 cm,
      varying inter-compression pauses) were delivered for 2 min each in a semi-random
      pattern, totaling 50 compression minutes. Linear Mixed Models were used to
      estimate the effect of compression waveform on hemodynamics. RESULTS: Blood flow
      and pressure decayed significantly with time in both arteries and veins. No
      waveform maximized blood flow in all vessels simultaneously and the waveform
      generating maximal blood flow in a specific vessel changed over time in all
      vessels. A flow mismatch between paired arteries and veins, e.g. abdominal aorta
      and inferior vena cava, also developed over time. The waveform with the slowest
      rate and shortest duty cycle had the smallest mismatch between flows after about
      30 min of CPR. CONCLUSIONS: This data challenges the concept of a single optimal
      CC waveform. Time dependent physiological response to compressions and no single
      compression waveform optimizing flow in all vessels indicate that current
      descriptions of CPR don't reflect patient physiology.

PMID- 30092278
TI  - Exploring strategies to reduce time span to bystander CPR in sudden cardiac
      arrest based on the mechanism of the witness acute stress response.

PMID- 30092279
TI  - Constructing atomic structural models into cryo-EM densities using molecular
      dynamics - Pros and cons.
AB  - Accurate structure determination from electron density maps at 3-5 A resolution
      necessitates a balance between extensive global and local sampling of atomistic
      models, yet with the stereochemical correctness of backbone and sidechain
      geometries. Molecular Dynamics Flexible Fitting (MDFF), particularly through a
      resolution-exchange scheme, ReMDFF, provides a robust way of achieving this
      balance for hybrid structure determination. Employing two high-resolution density
      maps, namely that of beta-galactosidase at 3.2 A and TRPV1 at 3.4 A, we showcase
      the quality of ReMDFF-generated models, comparing them against ones submitted by
      independent research groups for the 2015-2016 Cryo-EM Model Challenge. This
      comparison offers a clear evaluation of ReMDFF's strengths and shortcomings, and
      those of data-guided real-space refinements in general. ReMDFF results scored
      highly on the various metric for judging the quality-of-fit and quality-of-model.
      However, some systematic discrepancies are also noted employing a Molprobity
      analysis, that are reproducible across multiple competition entries. A space of
      key refinement parameters is explored within ReMDFF to observe their impact
      within the final model. Choice of force field parameters and initial model seem
      to have the most significant impact on ReMDFF model-quality. To this end, very
      recently developed CHARMM36m force field parameters provide now more refined
      ReMDFF models than the ones originally submitted to the Cryo-EM challenge.
      Finally, a set of good-practices is prescribed for the community to benefit from
      the MDFF developments.

PMID- 30092281
TI  - Comparison of ground sections, paraffin sections and micro-CT imaging of bone
      from the epiphysis of the porcine femur for morphometric evaluation.
AB  - The aim of this study was to compare data on the volume fraction of bone and the
      thickness of the cortical compact bone acquired during microcomputed tomography
      (micro-CT) analysis with data acquired from identical samples using stereological
      analysis of either decalcified paraffin sections or ground sections.
      Additionally, we aimed to compare adjacent tissue samples taken from the major
      trochanter of the porcine femur to map the basic biological variability of
      trabecular bone. Fifteen pairs of adjacent tissue blocks were removed from the
      major trochanter of the proximal epiphyses of porcine femurs (female pigs aged 24
      39 months, weight=59.16+/-8.15kg). In each sample, the volume of the cortical
      compact bone, the volume of the trabecular bone, and the thickness of the
      cortical compact bone was assessed using micro-CT. Afterwards, half of the
      samples were decalcified and processed using paraffin histological sections.
      Another half was processed into ground sections. The volume and thickness of bone
      was assessed in histological sections using stereological techniques. There were
      no significant differences in the bone volumes and thicknesses measured by micro
      CT and the corresponding values quantified in decalcified sections. Similarly,
      there were no differences between the results from micro-CT and the analysis of
      the corresponding ground sections. Histomorphometric studies based on relatively
      low numbers of undecalcified ground sections or demineralized paraffin sections
      of bone yield data on bone volume and the thickness of cortical compact bone that
      is comparable with three-dimensional micro-CT examination. The pilot data on the
      variability of cortical compact bone and trabecular bone volumes in the porcine
      major trochanter provided in this study aim for planning experiments in the field
      of bone healing and implantology.

PMID- 30092280
TI  - Rapid near-atomic resolution single-particle 3D reconstruction with SIMPLE.
AB  - Cryogenic electron microscopy (cryo-EM) and single-particle analysis enables
      determination of near-atomic resolution structures of biological molecules.
      However, large computational requirements limit throughput and rapid testing of
      new image processing tools. We developed PRIME, an algorithm part of the SIMPLE
      software suite, for determination of the relative 3D orientations of single
      particle projection images. PRIME has primarily found use for generation of an
      initial ab initio 3D reconstruction. Here we show that the strategy behind PRIME,
      iterative estimation of per-particle orientation distributions with stochastic
      hill climbing, provides a competitive approach to near-atomic resolution single
      particle 3D reconstruction. A number of mathematical techniques for accelerating
      the convergence rate are introduced, leading to a speedup of nearly two orders of
      magnitude. We benchmarked our developments on numerous publicly available data
      sets and conclude that near-atomic resolution ab initio 3D reconstructions can be
      obtained with SIMPLE in a matter of hours, using standard over-the-counter CPU
      workstations.

PMID- 30092282
TI  - RNA binding protein HuR regulates extracellular matrix gene expression and pH
      homeostasis independent of controlling HIF-1alpha signaling in nucleus pulposus
      cells.
AB  - Nucleus pulposus (NP) cells reside in the hypoxic niche of the intervertebral
      disc. Studies have demonstrated that RNA-binding protein HuR modulates hypoxic
      signaling in several cancers, however, its function in the disc is unknown. HuR
      did not show cytoplasmic translocation in hypoxia and its silencing did not alter
      levels of Hif-1alpha or HIF-targets in NP cells. RNA-Sequencing data revealed
      that important extracellular matrix-related genes including several collagens,
      MMPs, aggrecan, Tgf-beta3 and Sdc4 were regulated by HuR. Further analysis of HuR
      silenced NP cells confirmed that HuR maintained expression of these matrix genes.
      We confirmed decreased levels of secreted collagen I and Sdc4 and increased pro
      MMP13 in HuR-knockdown cells. In addition, messenger ribonucleoprotein
      immunoprecipitation demonstrated HuR binding to Tgf-beta3 and Sdc4 mRNAs.
      Interestingly, while HuR bound to Hif-1alpha and Vegf mRNAs, it was clear that
      compensatory mechanisms sustained their expression when HuR was silenced.
      Noteworthy, despite the presence of multiple HuR-binding sites and reported
      interaction in other cell types, HuR showed no binding to Pgk1, Eno1, Pdk1 and
      Pfkfb3 in NP cells. Metabolic studies showed a significant decrease in the
      extracellular acidification rate (ECAR) and mitochondrial oxygen consumption rate
      (OCR) and acidic pH in HuR-silenced NP cells, without appreciable change in total
      OCR. These changes were likely due to decreased Ca12 expression in HuR silenced
      cells. Taken together, our study demonstrates for the first time that HuR
      regulates extracellular matrix (ECM) and pH homeostasis of NP cells and has
      important implications in the maintenance of intervertebral disc health.

PMID- 30092283
TI  - Topological remodeling of cortical perineuronal nets in focal cerebral ischemia
      and mild hypoperfusion.
AB  - Despite the crucial role of perineuronal nets (PNNs) in neural plasticity and
      neurological disorders, their ultrastructural organization remains largely
      unresolved. We have developed a novel approach combining superresolution
      structured illumination microscopy (SR-SIM) and mathematical reconstruction that
      allows for quantitative analysis of PNN topology. Since perineuronal matrix is
      capable to restrict neural plasticity but at the same time is necessary to
      maintain synapses, we hypothesized that a beneficial post stroke recovery
      requires a reversible loosening of PNNs. Our results indicated that focal
      cerebral ischemia induces partial depletion of PNNs and that mild hypoperfusion
      not associated with ischemic injury can induce ultra-structural rearrangements in
      visually intact meshworks. In line with the activation of neural plasticity under
      mild stress stimuli, we provide evidence that topological conversion of PNNs can
      support post stroke neural rewiring.

PMID- 30092284
TI  - Singular and combined effects of transcranial infrared laser stimulation and
      exposure therapy: A randomized clinical trial.
AB  - This RCT will test whether transcranial infrared laser stimulation (TILS)
      administered immediately following standard exposure therapy enhances the
      retention of fear extinction for naturally acquired pathological fear. A second
      aim is to investigate the efficacy of TILS as a stand-alone intervention for
      reducing pathological fear. Participants with elevated fear in any one of the
      following four domains: (a) fear of enclosed spaces, (b) fear of contamination,
      (c) fear of public speaking, or (d) fear of anxiety (i.e., anxiety sensitivity)
      will be recruited from introductory psychology classes and the greater Austin
      community. Participants displaying marked fear responding will be stratified on
      baseline fear responding and fear domain and randomized to one of four treatment
      arms: (1) Exposure + TILS, (2) Exposure + sham TILS, (3) TILS alone, or (4) Sham
      TILS alone. We anticipate that TILS will enhance exposure therapy outcome
      relative to sham TILS and that this enhancement effect will be most pronounced
      for (a) those displaying higher baseline fear responding, and (b) those showing
      greater fear reduction during exposure. Study rationale as well as additional
      predictions and clinical implications are discussed.

PMID- 30092285
TI  - Dynamic Perception of Jasmonates by the F-Box Protein COI1.
AB  - Jasmonates (JAs) are cyclic fatty acid-derived phytohormones that regulate
      diverse aspects of plant defense and development. The endogenous active JA
      molecule (+)-7-iso-JA-L-Ile (JA-Ile) and its analog coronatine trigger formation
      of a complex with the F-box protein COI1 and JAZ repressors to induce degradation
      of the JAZs through the 26S proteasome pathway in a COI1-dependent manner. To
      reveal the formation process of COI1-JA-JAZ ternary complex, we employed several
      biochemical approaches to examine how JA is dynamically perceived. These analyses
      showed that the COI1 proteins of Arabidopsis and rice bind JA with appreciable
      binding affinity and revealed the kinetics and thermodynamics of the COI1-JA-JAZ
      ternary complex. Our results suggest that COI1 is the primary receptor perceiving
      the active JA molecule to initially form a COI1-JA complex that subsequently
      recruits JAZs for further signal transduction.

PMID- 30092286
TI  - Glucocorticoids promote intrinsic human TH17 differentiation.

PMID- 30092288
TI  - Janus kinase 2 activation mechanisms revealed by analysis of suppressing
      mutations.
AB  - BACKGROUND: Janus kinases (JAKs; JAK1 to JAK3 and tyrosine kinase 2) mediate
      cytokine signals in the regulation of hematopoiesis and immunity. JAK2 clinical
      mutations cause myeloproliferative neoplasms and leukemia, and the mutations
      strongly concentrate in the regulatory pseudokinase domain Janus kinase homology
      (JH) 2. Current clinical JAK inhibitors target the tyrosine kinase domain and
      lack mutation and pathway selectivity. OBJECTIVE: We sought to characterize
      mechanisms and differences for pathogenic and cytokine-induced JAK2 activation to
      enable design of novel selective JAK inhibitors. METHODS: We performed a
      systematic analysis of JAK2 activation requirements using structure-guided
      mutagenesis, cell-signaling assays, microscopy, and biochemical analysis.
      RESULTS: Distinct structural requirements were identified for activation of
      different pathogenic mutations. Specifically, the predominant JAK2 mutation,
      V617F, is the most sensitive to structural perturbations in multiple JH2 elements
      (C helix [alphaC], Src homology 2-JH2 linker, and ATP binding site). In contrast,
      activation of K539L is resistant to most perturbations. Normal cytokine signaling
      shows distinct differences in activation requirements: JH2 ATP binding site
      mutations have only a minor effect on signaling, whereas JH2 alphaC mutations
      reduce homomeric (JAK2-JAK2) erythropoietin signaling and almost completely
      abrogate heteromeric (JAK2-JAK1) IFN-gamma signaling, potentially by disrupting a
      dimerization interface on JH2. CONCLUSIONS: These results suggest that
      therapeutic approaches targeting the JH2 ATP binding site and alphaC could be
      effective in inhibiting most pathogenic mutations. JH2 ATP site targeting has the
      potential for reduced side effects by retaining erythropoietin and IFN-gamma
      functions. Simultaneously, however, we identified the JH2 alphaC interface as a
      potential target for pathway-selective JAK inhibitors in patients with diseases
      with unmutated JAK2, thus providing new insights into the development of novel
      pharmacologic interventions.

PMID- 30092287
TI  - Allergic airway sensitization impairs antibacterial IgG antibody responses during
      bacterial respiratory tract infections.
AB  - BACKGROUND: Mycoplasma pneumoniae, an atypical human pathogen, has been
      associated with asthma initiation and exacerbation. Asthmatic patients have been
      reported to have higher carriage rates of M pneumoniae compared with nonasthmatic
      subjects and are at greater risk for invasive respiratory infections. OBJECTIVE:
      We sought to study whether prior allergen sensitization affects the host response
      to chronic bacterial infection. METHODS: BALB/cJ and IL-4 receptor alpha-/- mice
      were sensitized with ovalbumin (OVA) and then infected with M pneumoniae or
      Streptococcus pneumoniae. Immune parameters were analyzed at 30 days
      postinfection and included cellular profiles in bronchoalveolar lavage fluid
      (BALF) and serum IgG and IgE antibody levels to whole bacterial lysate,
      recombinant P1 adhesin, and OVA. Total lung RNA was examined for transcript
      levels, and BALF was examined for cytokine protein profiles. RESULTS: Anti-M
      pneumoniae antibody responses were decreased in allergen-sensitized, M pneumoniae
      infected animals compared with control animals, but OVA-specific IgG responses
      were unaffected. Similar decreases in anti-S pneumoniae antibody levels were
      found in OVA-sensitized animals. However, M pneumoniae, but not S pneumoniae,
      infection augmented anti-OVA IgE antibody responses. Loss of IL-4 receptor
      signaling partially restored anti-M pneumoniae antibody responses in IgG2a and
      IgG2b subclasses. Inflammatory cytokine levels in BALF from OVA-sensitized, M
      pneumoniae-infected or S pneumoniae-infected animals were reduced compared with
      those in uninfected OVA-sensitized control animals. Unexpectedly, airway
      hyperreactivity to methacholine was essentially ablated in M pneumoniae-infected,
      OVA-sensitized animals. CONCLUSIONS: An established type 2-biased host immune
      response impairs the host immune response to respiratory bacterial infection in a
      largely pathogen-independent manner. Some pathogens, such as M pneumoniae, can
      augment ongoing allergic responses and inhibit pulmonary type 2 cytokine
      responses and allergic airway hyperreactivity.

PMID- 30092289
TI  - Jakinibs for the treatment of immune dysregulation in patients with gain-of
      function signal transducer and activator of transcription 1 (STAT1) or STAT3
      mutations.

PMID- 30092291
TI  - Survey of screening methods, rates and policies for the detection of
      carbapenemase-producing Enterobacteriaceae in English hospitals.
AB  - Multi-drug-resistant Gram-negative bacteria are of major clinical concern. The
      increasing prevalence of carbapenemase-producing Enterobacteriaceae (CPE),
      resistant to all beta-lactams including carbapenems and able to colonize the
      large intestine, represents a key threat. Rapid, accurate detection of intestinal
      CPE colonization is critical to minimize transmission, and hence reduce costly,
      difficult-to-treat CPE infections. There is currently no 'gold standard' CPE
      detection method. A survey of diagnostic laboratories in England found
      considerable heterogeneity in diagnostic CPE testing methods and procedures.

PMID- 30092290
TI  - Fighting the good fight: the fallout of fake news in infection prevention and why
      context matters.
AB  - Although misinformation has always existed, the scope and speed at which fake
      news can reach even the most remote corners of the globe is a modern phenomenon.
      In the field of infection prevention and control (IPC), we like to believe that
      our dedication to the field and the process of conducting science protects us
      from the ravages of 'bad buzz' and fake news. This misconception leads medical
      professionals to underestimate the negative effects of misinformation on public
      health. This paper focuses on the nexus of what is happening between the field of
      IPC and the public. Its aim is to examine how information gets distorted and
      amplified between the medical community and the public, and outline some of the
      issues that deserve further attention. It looks at a number of case studies which
      show that even one badly conducted study can have a severe negative impact on
      public health, and that a well-conducted study can be distorted to make people
      believe something fallacious. In the current system of publishing and the
      proliferation of online journals that publish without peer review, 'bad buzz' and
      fake news can quickly do a good deal of damage.

PMID- 30092292
TI  - Guidance for the decontamination of intracavity medical devices: the report of a
      working group of the Healthcare Infection Society.
AB  - BACKGROUND: Intracavity medical devices (ICMDs) are used in a wide variety of
      healthcare settings. The approach to their decontamination and the resources
      available also differ widely. Their potential for infection transmission is
      considerable. AIM: To produce a comprehensive risk assessment-based approach to
      the decontamination of ICMDs, accompanied by an adaptable audit tool. KEY
      RECOMMENDATIONS: 

PMID- 30092293
TI  - The validity of adenosine triphosphate measurement in detecting endoscope
      contamination.
AB  - BACKGROUND: Endoscopic procedures are vital to gastrointestinal disease diagnosis
      and management, but risk infection transmission. In Australia, endoscopes undergo
      monthly-to-quarterly microbiological testing, to prevent patient infection.
      Endoscopes are used more frequently, meaning contamination may not be detected by
      this surveillance before infection transmission occurs. AIM: To evaluate the use
      of adenosine triphosphate (ATP) measurement, alongside standard microbiological
      cultures, in detecting endoscope contamination before high-level disinfection.
      Using these results, we also aimed to confirm the efficacy of manual cleaning in
      reducing levels of ATP and cfu/mL. METHODS: Seventeen in-clinical-use
      gastroscopes and 24 in-clinical-use colonoscopes from the Liverpool Hospital
      Endoscopy unit were sampled across three separate cleaning stages before high
      level disinfection. Colony counts and ATP measurements were then performed on
      these samples. FINDINGS: The correlation between the cfu/mL and RLU of samples
      collected from colonoscopes was 0.497 (95% confidence interval: 0.28-0.66; P <
      0.0001). The correlation between cfu/mL and RLU for samples collected from
      gastroscopes was 0.377 (0.08-0.61; P = 0.0138). RLU and cfu/mL values were shown
      to fall significantly (P < 0.005) following precleaning and manual cleaning.
      CONCLUSION: There was a significant correlation between ATP and cfu/mL measured
      from samples collected before high-level disinfection. Precleaning and manual
      cleaning were shown to reduce ATP and microbiological load significantly. ATP
      measurement can be performed within minutes with little training and produces
      results that are easy to interpret. These findings warrant further research on
      the utility of ATP measurement as a screening tool for detecting endoscope
      contamination after high-level disinfection.

PMID- 30092294
TI  - The unknown role of disinfectant-detergents for failure of effective endoscope
      reprocessing.

PMID- 30092295
TI  - Combination of microdissection and single cell quantitative real-time PCR
      revealed intercellular mitochondrial DNA heterogeneities in fibroblasts of Kearns
      Sayre syndrome patients.
AB  - Kearns-Sayre syndrome (KSS) is a multisystemic disorder marked by aerobic cell
      metabolism dysfunction. Fibroblasts derived from KSS patient skin biopsy exhibit
      heterogeneous occurrence of mitochondrial genomes as those circular DNA molecules
      partially carry the common deletion. In our approach, we aim to evaluate the
      intercellular alterations in respect to mitochondrial DNA integrity by laser
      capture microdissection and multiplex quantitative real-time PCR in single cells.
      The obtained results give new insights into the understanding of mitochondrial
      genetics, e.g. postulated sorting of damaged mitochondria, and heterogeneity of
      cells. Further, we discuss the relevance of intercellular heterogeneities for
      human mitochondrial disorders in general.

PMID- 30092296
TI  - Cynomorium songaricum prevents bone resorption in ovariectomized rats through
      RANKL/RANK/TRAF6 mediated suppression of PI3K/AKT and NF-kappaB pathways.
AB  - AIM: Cynomorium songaricum Rupr., an edible and important Traditional Chinese
      medicine has long been used in folk for treatment of kidney deficiency, was
      chosen to estimate the antiosteoporotic activity and underlying molecular
      mechanism on rats induced by ovariectomy (OVX). MAIN METHODS: 9 of 45 rats were
      underwent bilateral laparotomy without removing the ovaries as sham group,
      remains were underwent bilateral ovariectomy and equally randomized into four
      groups: with vehicle (0.5% CMC-Na) as model group, estradiol valerate (1 mg/kg
      body weight/day) as positive control, with 100 and 300 mg/kg body weight/day of
      ethanol extracts of C. songaricum extract (CSE) as low and high dosage groups,
      respectively. KEY FINDINGS: After 12 weeks of continues orally intervention, the
      decreases of bone mineral density, bone mineral content, tissue mineral content,
      as well as the increases of bone trabecular separation and bone resorption
      markers were significantly reversed by CSE in the OVX rats, and in particular, a
      contradictory phenomenon on calcium and phosphorus contents was observed and
      elucidated. Mechanistically, the expressions of tumor-necrosis factor receptor
      associated factor 6 (TRAF 6), nuclear factor kappa B (RANK) and its ligand
      (RANKL), as well as the nuclear factor kappa B (NF-kappaB), phosphoinositide 3
      kinase (PI3K) and protein kinase B (AKT) levels were significantly down-regulated
      by CSE intervention, whereas the osteoprotegerin (OPG) was significantly up
      regulated by CSE as compared to the control. SIGNIFICANCE: Concisely, C.
      songaricum exhibited potential therapeutic effect on bone metabolism of
      ovariectomized rats, and this effect was possibly exerted by RANKL/RANK/TRAF6
      mediated down-regulation of NF-kappaB and PI3K/AKT pathways.

PMID- 30092298
TI  - MiR-21 regulates the ACAT1 gene in MCF-7 cells.
AB  - AIMS: The purpose of the present study was to determine whether miR-21 regulates
      the human ACAT1 gene. We also assessed whether transfection of MCF-7 cells with
      miR-21 mimic/inhibitor leads to changes in ACAT1 mRNA/protein levels, cell
      proliferation rate, or apoptosis. MAIN METHODS: Regulation of ACAT1 3'UTR by miR
      21 was evaluated using a dual-luciferase reporter assay. The effect of miR-21 on
      mRNA/protein levels of ACAT1 and PTEN (confirmed as an important target of miR-21
      for comparison) was measured by qPCR/western blot analysis and immunostaining.
      Proliferation rate was determined by cell counting. Percentage of cells
      undergoing late apoptosis was determined by staining with Hoechst 33342/propidium
      iodide. KEY FINDINGS: Dual-luciferase reporter assay confirmed the regulation of
      ACAT1 3'UTR by miR-21. Furthermore, transfection of MCF-7 cells with miR-21 mimic
      decreased mRNA and protein levels of ACAT1 and PTEN genes. In contrast, miR-21
      inhibition increased the mRNA and protein levels of both genes studied. Finally,
      we observed an increase in cell proliferation and decrease in the percentage of
      cells in late apoptosis in MCF-7 cells transfected with miR-21 mimic, whereas
      transfection with miR-21 inhibitor led to the opposite effect. SIGNIFICANCE: Our
      data confirm the hypothesis that miR-21 regulates the human ACAT1 gene. As the
      expression of this microRNA is altered in many types of cancers, the discovery of
      novel targets for miR-21 is of particular interest for diagnosis and treatment.

PMID- 30092297
TI  - Increased branched-chain amino acid levels are associated with long-term adverse
      cardiovascular events in patients with STEMI and acute heart failure.
AB  - AIMS: The long-term prognosis of ST-segment elevation myocardial infarction
      (STEMI) with acute heart failure (AHF) is poor. Identification of metabolic
      changes could provide understanding of the underlying pathological progress
      associated with adverse events in patients with STEMI and AHF. Therefore, the
      study aimed to identify new plasm metabolites associated with long-term adverse
      cardiovascular events in patients with STEMI and AHF. MATERIALS AND METHODS: Mass
      spectrometry measurements of 26 amino acids were performed in 138 patients with
      STEMI and AHF. Endpoints were adverse cardiac events (composite of death and
      heart failure hospitalization). Survival analysis was performed to determine
      independent predictors of amino acids. KEY FINDINGS: During a 3-year follow-up,
      there were 32 deaths and 21 hospitalizations for heart failure (HF).
      Multivariable Cox regression analysis showed that branched-chain amino acid
      (BCAA) levels were independent predictors for adverse cardiovascular events in
      patients with STEMI and AHF (adjusted HR: 2.67, p < 0.001). The prognostic value
      of BCAA was better than that of N-terminal pro-B-type natriuretic peptide (area
      under the curve: 0.77 vs. 0.72) and Kaplan-Meier curves for adverse cardiac
      events (log-rank: 14.91 vs. 10.05). The combination of BCAAs and NT-proBNP
      yielded a stronger predictive value (area under the curve: 0.81, log-rank:
      27.14). Importantly, addition of BCAAs and NT-pro BNP to the Global Registry of
      Acute Coronary Events score increased the C-statistic from 0.707 to 0.813, with a
      net reclassification improvement of 0.714. SIGNIFICANCE: Our study shows that
      increased plasma BCAA levels are associated with long-term adverse cardiovascular
      events in patients with STEMI and AHF. These findings suggest that dysregulated
      BCAA metabolism pathways affect clinical outcome after STEMI with AHF.

PMID- 30092299
TI  - Polydatin attenuates reactive oxygen species-induced airway remodeling by
      promoting Nrf2-mediated antioxidant signaling in asthma mouse model.
AB  - Reactive oxygen species (ROS) and epithelial-mesenchymal transition (EMT) play a
      critical role in transforming growth factor (TGF)-beta1-mediated fibrotic airway
      remodeling in asthma. Polydatin (PD) is a small natural molecule in Chinese
      medicine; it is isolated from Polygonum cuspidatum and has antioxidative
      properties. In this study, we aimed to determine whether PD was protective
      against ROS-induced pulmonary fibrosis in asthma. Ovalbumin (OVA) was used to
      induce asthma in a mouse model that was treated with or without PD. We also
      created nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown BEAS-2B
      cells and investigated whether PD reversed TGF-beta1-induced pulmonary epithelial
      cell EMT by promotion of Nrf2-mediated antioxidation. Immunofluorescence showed
      that ROS and TGF-beta1 expression was significantly increased in lung tissue from
      the OVA-induced asthma model. PD treatment inhibited activity of ROS and TGF
      beta1. Immunohistochemistry showed that PD treatment decreased OVA-induced lung
      ROS, TGF-beta1 expression and fibroblasts. Western blotting showed that PD
      treatment reversed OVA-induced NADPH oxidase (NOX)1/4 expression by promoting
      Nrf2-mediated heme oxygenase-1 and NADPH dehydrogenase (quinone)-1 expression. PD
      treatment suppressed OVA-induced EMT and lung fibroblast protein expression in
      lung tissue. Nrf2 downregulation suppressed the protective effect of PD by
      promoting TGF-beta1-induced ROS and EMT and accumulation of extracellular-matrix
      related protein. All these data indicate that PD has potential therapeutic
      effects in asthma by promoting Nrf2-mediated antioxidation.

PMID- 30092300
TI  - Epigallocatechin-3-gallate protects against 1,3-dichloro-2-propanol-induced lipid
      accumulation in C57BL/6J mice.
AB  - AIMS: Chloropropanol is a contaminant produced during food processing, and 1,3
      dichloro-2-propanol (1,3-DCP) is one of the most-studied and most common
      chloropropanol-related food contaminants. Epigallocatechin-3-gallate (EGCG) is
      the most abundant ester catechin in tea polyphenols. We studied the potential
      therapeutic effect of EGCG on 1,3-DCP-induced lipid accumulation in the liver of
      mice, and determined the related regulatory mechanisms. MATERIALS AND METHODS:
      The effects of EGCG were investigated in 6-8-week-old adult male C57BL/6J mice
      that were given 1,3-DCP (1 mg/kg bw/day; i.g.) for 6 weeks. EGCG (10, 31.6 and
      100 mg/kg bw/day i.g.) was administered daily in the 1,3-DCP-treated mice for 10
      days. Total cholesterol (TC) and triglyceride (TG) were measured in serum and
      liver. For histological examination, HE staining and oil red O experiments were
      performed. Western blot and quantitative RT-PCR were subsequently used to study
      the molecular mechanisms. KEY FINDINGS: Increasing concentrations of EGCG
      significantly lowered TC and TG levels compared with those of the model group.
      Furthermore, EGCG dramatically increased expression of cAMP, P-PKA and P-CREBP, 
      AMPKalpha (Tr172), LKB1, P-ACC (Ser79) and lowered expression of CD36, SREBP-2,
      HMGCR, SREBP-1, GPAT in 1,3-DCP-treated mice livers. Quantitative RT-PCR
      experiments showed that EGCG regulated gene transcription of AMPK, SREBF-2, HMGCR
      and SREBP-1c. SIGNIFICANCE: These data suggested that EGCG intervention restored
      1,3-DCP-altered protein levels and reduced hepatic lipid levels to normal. The
      mechanism was mediated by the AMPK and PKA pathways. EGCG may be developed as a
      candidate natural agent for the treatment of 1,3-DCP-induced lipid accumulation.

PMID- 30092301
TI  - The Impact of Teaching on Fundamental General Urologic Procedures: Do Residents
      Help or Hurt?
AB  - OBJECTIVE: To examine the effects of trainee involvement on fundamental urology
      procedures. METHODS: Current Procedural Terminology codes were used to identify
      patients within the National Surgical Quality Improvement Program database who
      underwent a selection of fundamental general urology procedures (2005-2013).
      Operative time and perioperative complications (30-day) were compared between
      cases with and without trainee involvement. RESULTS: 29,488 patients had general
      urology procedures with information regarding trainee involvement, 13,251 (44.9%)
      with trainee involvement, and 16,237 (55.1%) without. Overall patients who
      underwent procedures with trainee involvement were younger and had fewer
      comorbidities (Table 1). Trainee involvement showed significant increase in
      operative time in all procedures included in the study (Table 2). On multivariate
      analysis trainee involvement increased the risk of complications (Odds Ratio (OR)
      1.61, 95% CI 1.45-1.78, P < .001). Other factors that increased the risk of
      complications were: American Society of Anesthesiologists (ASA) class 3-4 (OR
      2.01, 95% CI 1.46-2.77, P < .001), partially or totally dependent functional
      status (OR 2.22, 95% CI 1.68-2.94, P < .001), diabetes mellitus (OR 1.21, 95% CI
      1.05-1.39, P = .008), heart disease (OR 1.19, 95% CI 1.02-1.38, P = .027), and
      respiratory disease (OR 1.33, 95% CI 1.09-1.63, P = .027). CONCLUSION: While
      trainees are valuable members of the urology team at teaching hospitals and
      training is necessary, their involvement in urologic surgery appears to increase
      operative time for all procedures and complications in certain procedures.
      Further research needs to be done on how to mitigate these effects while
      preserving surgical education quality.

PMID- 30092302
TI  - Congenital Duplication of the Urogenital Sinus in an Adult Female.

PMID- 30092303
TI  - Effects of Feminizing Hormones on Sperm Production and Malignant Changes:
      Microscopic Examination of Post Orchiectomy Specimens in Transwomen.
AB  - OBJECTIVE: To examine post-orchiectomy specimens of transgender individuals to
      better understand the reproductive implications of hormonal therapy and to look
      for potential malignant or premalignant changes. MATERIALS AND METHODS: A
      retrospective chart review was performed on the orchiectomy specimens from 135 TG
      individuals who underwent bilateral simple orchiectomy (54) or vaginoplasty with
      combined orchiectomy (81) at a single institution from 2014-2017. Factors
      examined included microscopic evidence of spermatogenesis, weight of specimens,
      evidence of malignant or premalignant changes, and patient demographic
      information. RESULTS: Four percent (6/135) of all orchiectomy specimens had
      normal spermatogenesis in both testicles. Twenty-one percent (28/135)
      demonstrated some stage of spermatogenesis, of which 61% (17/28) were in
      maturational arrest. The median patient age at surgery was 30years (range 18-76).
      Median overall testicle weight was 24g (range 10.4-71.1), compared with 24g
      (range 10-71g) in testicles without evidence of spermatogenesis and 26g (range
      17.9-40.9) in testicles with normal spermatogenesis. None of the specimens
      demonstrated premalignant or malignant changes. CONCLUSION: Up to 21% of
      individuals undergoing a gender affirming surgery had microscopic evidence of
      spermatogenesis in varying stages. Furthermore, 4% of individuals had normal
      spermatogenesis. None of the specimens had malignant or premalignant changes.
      These findings may have implications for counseling transgender individuals on
      sexual and reproductive health and highlight the need for further research in
      this sector.

PMID- 30092304
TI  - Validation of a Simulation-training Model for Robotic Intracorporeal Bowel
      Anastomosis Using a Step-by-step Technique.
AB  - OBJECTIVE: To develop and validate a training model for the robotic
      intracorporeal bowel anastomosis. METHODS: For simulation, surgeons with varying
      levels of experience were instructed about bowel anastomosis robotic surgical
      simulation in a short educational video. All participants performed the required
      steps for the intracorporeal bowel anastomosis under standardized conditions. The
      procedure consists of the following steps: division of the bowel with a stapler
      (1), incision and opening of the bowel limbs at the antimesenteric angle (2),
      insertion of the stapler into the 2 bowel limbs for the side-to-side anastomosis
      (3), and transverse closure of the anastomosis with the stapler (4). All
      simulations were performed using the daVinci SI robotic system. Face and content
      validity were assessed using a standardized questionnaire. Construct validity was
      evaluated using the Global Evaluative Assessment of Robotic Skills, a validated
      global performance rating scale. RESULTS: Twenty-two surgeons participated
      including 6 robotic experts and 16 trainees. The expert participants rated the
      bowel anastomosis model highly for face validity (median 4/5; 64% agree or
      strongly agree), and all participants rated the content as a training model very
      highly (median 4.5/5; 100% agree or strongly agree). Discrimination between
      experts and trainees using Global Evaluative Assessment of Robotic Skills
      demonstrated construct validity (novice 17.6 vs expert 24.7, P = .03).
      CONCLUSION: We demonstrate that the bowel anastomosis robotic surgical simulator
      is a reproducible and realistic simulation that allows for an objective skills
      assessment. We establish face, content, and construct validity for this model.
      This step-by-step technique may be utilized in training surgeons desiring to
      acquire skills in robotic intracorporeal urinary diversion.

PMID- 30092306
TI  - Assessment of poly(3-hydroxybutyrate) synthesis from a novel obligate
      alkaliphilic Bacillus marmarensis and generation of its composite scaffold via
      electrospinning.
AB  - In this study, poly(3-hydroxybutyrate) (PHB) production from a newly isolated
      obligate alkaliphilic Bacillus marmarensis DSM 21297 was investigated to evaluate
      the ability of obligate alkaliphilic strain to produce a biopolymer.
      Additionally, electrospun nanofibers from B. marmarensis PHB (Bm-PHB) were
      generated using Bm-PHB/polycaprolactone (PCL) blend to evaluate the applicability
      of Bm-PHB. According to the experimental results, the metabolic activity of B.
      marmarensis decreased the pH of the medium by generating H+ ions to initiate Bm
      PHB production, which was achieved at pH below 9.0. Regarding medium components,
      the addition of MgSO4.7H2O and KH2PO4 to the medium containing 1% glucose
      enhanced the amount of Bm-PHB synthesis, and an approximately 60% increase in PHB
      concentration was obtained in the presence of mineral salts. Based on FTIR
      analysis, the chemical structures of Bm-PHB and commercial PHB were found to be
      highly similar. Additionally, the Tg and Tm values of Bm-PHB were determined to
      be 17.77  degrees C and 165.17  degrees C, respectively. Moreover, Bm-PHB/PCL
      composite scaffold was generated by electrospinning method that produced
      nanofibers between 150 and 400 nm in diameter, with an average of 250 nm. To our
      knowledge, this is the first report to produce PHB from an obligate alkaliphilic
      Bacillus strain and PHB scaffold.

PMID- 30092305
TI  - Clinical outcome and risk factors for failure in late acute prosthetic joint
      infections treated with debridement and implant retention.
AB  - OBJECTIVES: Debridement, antibiotics and implant retention (DAIR) is the
      recommended treatment for all acute prosthetic joint infections (PJI), but its
      efficacy in patients with late acute (LA) PJI is not well described. METHODS:
      Patients diagnosed with LA PJI between 2005 and 2015 were retrospectively
      evaluated. LA PJI was defined as the development of acute symptoms (<= 3 weeks)
      occurring >= 3 months after arthroplasty. Failure was defined as: (i) the need
      for implant removal, (ii) infection related death, (iii) the need for suppressive
      antibiotic therapy and/or (iv) relapse or reinfection during follow-up. RESULTS:
      340 patients from 27 centers were included. The overall failure rate was 45.0%
      (153/340). Failure was dominated by Staphylococcus aureus PJI (54.7%, 76/139).
      Significant independent preoperative risk factors for failure according to the
      multivariate analysis were: fracture as indication for the prosthesis (odds ratio
      (OR) 5.4), rheumatoid arthritis (OR 5.1), age above 80 years (OR 2.6), male
      gender (OR 2.0) and C-reactive protein > 150 mg/L (OR 2.0). Exchanging the mobile
      components during DAIR was the strongest predictor for treatment success (OR
      0.35). CONCLUSION: LA PJIs have a high failure rate. Treatment strategies should
      be individualized according to patients' age, comorbidity, clinical presentation
      and microorganism causing the infection.

PMID- 30092307
TI  - Manipulating the structure of medium-chain-length polyhydroxyalkanoate (MCL-PHA)
      to enhance thermal properties and crystallization kinetics.
AB  - We investigated the effects of the structure of medium-chain-length
      polyhydroxyalkanoates (MCL-PHAs) on their thermal properties and crystallization
      kinetics. The predominantly homopolymeric poly(3-hydroxydecanoate), P(3HD)-98,
      and the poly(3-hydroxydodecanoate), P(3HDD), exhibited sharp crystallization
      peaks upon cooling, with the latter exhibiting faster crystallization rates. A
      chemical modification strategy involving reaction with dicumyl peroxide and
      triallyl trimesate coagent was implemented to introduce branching and enhance the
      crystallization kinetics of P(3HD-98). Increases in the exothermic
      crystallization temperature by 8  degrees C and in the overall crystallinity of
      the P(3HD)-98 were observed upon chemical modification. The Avrami
      crystallization kinetic parameters obtained by fitting the isothermal
      crystallization data revealed a significant increase in the crystallization rate
      of the modified P(3HD)-98.

PMID- 30092308
TI  - The temperature-responsive hydroxybutyl chitosan hydrogels with polydopamine
      coating for cell sheet transplantation.
AB  - The aim of this study was to develop an effective cell sheet translocation method
      using a cell adhesive and temperature-responsive hydroxybutyl chitosan hydrogel
      (HBC). The polydopamine (PD)-coated HBC hydrogels were prepared by the dopamine
      self-polymerization on the surface of HBC hydrogel with different coating time,
      termed as P30, P60 and P120, respectively. Gelling property of HBC was not
      affected by PD coating. The PD-coated HBC hydrogels promoted the attachment and
      proliferation of mouse fibroblast cells (L929) and human umbilical vein
      endothelial cells (HUVECs), and allowed formation of monolayer cell sheet. In
      vitro translocation of HUVECs sheet could be obtained successively through phase
      transition of PD coated HBC hydrogel from gel to sol, and the cells sheet
      transferred from P30 hydrogel to a round cell coverglass maintained relatively
      complete monolayer and normal cell morphology. The results showed that P30
      hydrogel has the potential to be used for cell transplantation therapy.

PMID- 30092309
TI  - Ampholytic ion-exchange materials coated with small zwitterions for high-efficacy
      purification of ionizable soluble biomacromolecules.
AB  - For the purification of soluble proteins and nucleic acids through ion-exchange,
      the ampholytic ion-exchange materials (AIEMs) were designed, which possessed both
      short aliphatic carboxyl and short aliphatic amines/imidazole at optimized ratios
      on solid supports coated with high density of small zwitterions; under optimized
      conditions, the soluble ionizable biomacromolecules were adsorbed on those AIEMs
      via electrostatic attractions and eluted effectively through electrostatic
      repulsions. As the proof-of-concept, magnetic submicron particles bearing short
      aliphatic carboxyl and the coats of small zwitterion served as the starting solid
      supports, which were conjugated with lysine alone, or with lysine plus glycine or
      N,N-dimethylethylenediamine, to yield magnetic AIEMs whose surfaces possessed
      zero net charges at different pH. Such magnetic AIEMs exhibited ideal efficacy to
      release acid red 13 as an anion at the elution pH optimized for strong
      electrostatic repulsions; those magnetic AIEMs were proven absorbing under
      optimized conditions for the purification of soluble proteins stable at pH close
      to their isoelectric points and solid-phase extraction of nucleic acids in
      applicable biological mixtures. Therefore, the designed AIEMs are promising for
      the high-efficacy purification of ionizable soluble biomacromolecules.

PMID- 30092310
TI  - Zinc-chitosan nanoparticles induced apoptosis in human acute T-lymphocyte
      leukemia through activation of tumor necrosis factor receptor CD95 and apoptosis
      related genes.
AB  - Chitosan (CS), a novel biomaterial is widely used as a drug nano-carrier for
      cancer treatments. Towards this aim, anticancer and antibacterial activities of
      CS-nanoparticles-linked zinc (Zn-CSNPs) were evaluated. The particle size of
      CSNPs was lowered (113.09 nm) compared to Zn-CSNPs (160.7 nm). Both nanoparticles
      (CSNPs and Zn-CSNPs) were spherical in shape, polydispersive and homogenous.
      Fourier transforms infrared spectrophotometer (FTIR) and energy dispersive X-ray
      spectroscopy (EDX) analysis confirmed the different molecular arrangement of NPs
      and the presence of Zn in Zn-CSNPs and CS in both NPs, respectively. Zn-CSNPs had
      higher inhibitory activity against tested pathogens with a minimal inhibitory
      concentration (MIC) of 9.25-13.5 MUg.mL-1 and showed the complete inhibition of
      Staphylococcus aureus and Escherichia coli. Zn-CSNPs have triggered the apoptosis
      through activation of first apoptosis signal receptor/cluster of differentiation
      95 (Fas/CD95), and apoptotic-regulatory genes and caused 65-70% of cellular
      damage in human acute T-lymphocyte leukemia (6T-CEM) cells. Overall,
      internalizing properties of Zn from CSNPs is a promising therapeutic approach to
      treat Zn-deficiency related diseases particularly human acute leukemia (HAL).

PMID- 30092311
TI  - Competitive learning modulates memory consolidation during sleep.
AB  - Competition between memories can cause weakening of those memories. Here we
      investigated memory competition during sleep in human participants by presenting
      auditory cues that had been linked to two distinct picture-location pairs during
      wake. We manipulated competition during learning by requiring participants to
      rehearse picture-location pairs associated with the same sound either
      competitively (choosing to rehearse one over the other, leading to greater
      competition) or separately; we hypothesized that greater competition during
      learning would lead to greater competition when memories were cued during sleep.
      With separate-pair learning, we found that cueing benefited spatial retention.
      With competitive-pair learning, no benefit of cueing was observed on retention,
      but cueing impaired retention of well-learned pairs (where we expected strong
      competition). During sleep, post-cue beta power (16-30 Hz) indexed competition
      and predicted forgetting, whereas sigma power (11-16 Hz) predicted subsequent
      retention. Taken together, these findings show that competition between memories
      during learning can modulate how they are consolidated during sleep.

PMID- 30092312
TI  - Developmental prefrontal mRNA expression of D2 dopamine receptor splice variants
      and working memory impairments in rats after early life Interleukin-1beta
      elevation.
AB  - Long (D2L) and Short (D2S) isoforms of D2 dopamine receptor differ in their
      biochemical and physiological properties, which could affect functioning of
      prefrontal cortex. Contribution of distinct D2 dopamine receptor isoforms to
      cognitive dysfunctions and its developmental regulation are currently not fully
      elucidated. In the present study, we evaluated developmental mRNA expression of
      D2S/D2L dopamine receptor isoforms within the rat medial prefrontal cortex (mPFC)
      in the model of neurodevelopmental cognitive dysfunction. Working memory
      performance (Y-maze spontaneous alternations) and D2S/D2L mRNA expression in the
      mPFC (by qRT-PCR) were evaluated in juvenile (P27), adolescent (P42-47) and adult
      (P75-90) rats after chronic early life treatment with proinflammatory cytokine
      interleukin (IL)-1beta (1 ug/kg i.p. daily P15-21). It was shown that IL-1beta
      elevation during the 3rd week of life leads to working memory deficit originating
      in juvenile animals and persisting into adulthood. D2S mRNA expression was
      strongly downregulated during adolescence, and such downregulation was
      exaggerated in animals injected with IL-1beta during P15-21. Early life IL-1beta
      administrations influenced developmental changes in the D2S/D2L mRNA ratio. This
      measure was found to be decreased in adolescent and adult control (intact and
      vehicle-treated) rats compared to juvenile control, while in the case of IL-1beta
      treated animals, the decrease in D2S/D2L ratio was observed only in adulthood but
      not in adolescence compared to juvenile rats. During the adolescence, D2S mRNA
      expression was downregulated and D2S/D2L ratio was upregulated in the mPFC of
      rats treated with IL-1beta during the 3rd week of life compared to controls.
      Based on these data we conclude that changes in the developmental expression of
      D2 dopamine receptor splice variants within mPFC may underlie long-lasting
      cognitive deficit associated with neonatal pathology.

PMID- 30092313
TI  - Accuracy of mammography and clinical breast examination in the implementation of
      breast cancer screening programs in Colombia.
AB  - Most evidence on breast cancer screening accuracy derives from high income
      countries. We evaluated screening accuracy and factors related to program
      implementation in Bogota, Colombia. Between 2008 and 2012 participants underwent
      clinical breast examination (CBE) and mammography. Positive results underwent
      histological verification. Adherence to screening protocols was analyzed.
      Sensitivity, specificity, and predictive values were estimated and adjusted by
      overdiagnosis. Impact of alternative screening algorithms on follow-up was
      explored, including combined screening tests and modified coding systems for
      mammography. In total, 7436 women aged 50-69 were enrolled; 400 discontinued and
      1003 non-compliant with screening protocols. 23 cancer cases were diagnosed.
      Mammography sensitivity and specificity were 78.3% (95%CI 77.3-99.3) and 99.4%
      (95%CI 99.2-99.6). CBE sensitivity was 39.1% (95%CI 37.9-40.3) and specificity
      83.4% (95%CI 82.6-84.3). Parallel mammography and CBE showed the highest
      sensitivity (95.6%) and combined as serial tests the lowest (positive CBE
      followed by mammography 13.0%). A simplified coding system for mammography
      (recall/no-recall) had 6.3% of positive results and a minor reduction in
      specificity compared with standard mammography, but reported the best balance
      between recall rates and screening protocol compliance. Call-backs had high rates
      of loss-to-follow-up; thus, alternative screening algorithms might help increase
      screening compliance and follow-up in low and middle income countries,
      particularly in populations with poor screening history and low access to health
      services.

PMID- 30092315
TI  - Skin innate immunity of diskless-fingered odorous frogs (Odorrana grahami) with
      spatial-temporal variations.
AB  - The skin innate immunities of diskless-fingered odorous frogs (Odorrana grahami)
      from three populations were investigated. The antimicrobial capacities of skin
      secretions against the 60 representative environmental bacterial strains were
      evaluated using the values of the minimum inhibitory concentration (MIC)
      equivalents, which were defined as the volumes of antimicrobial solution just
      inhibiting the tested bacteria per 1 cm2 of surface area, from 0.06 to 9.10
      mL/cm2. Our results revealed significantly different skin antimicrobial
      capacities among the three populations: Mianning < Huili < Kunming. Within the
      frog population, the skin antimicrobial capacities are highly variable depending
      on the season: in Mianning frogs, summer < autumn and spring; in Huili frogs,
      spring < autumn < summer; in Kunming frogs, autumn < spring < summer. The animal
      density and body mass significantly impacted the skin antimicrobial capacity,
      while the sex ratio and soil or water bacterial counts did not.

PMID- 30092314
TI  - Neighborhood walkability and physical activity among older women: Tests of
      mediation by environmental perceptions and moderation by depressive symptoms.
AB  - Features that enhance neighborhood walkability (higher population density, street
      connectivity and access to destinations) are associated with higher levels of
      physical activity among older adults. The perceived neighborhood environment
      appears to mediate associations between the objective built environment and
      physical activity. The role of depressed mood in these associations is poorly
      understood. We examined the degree to which depressive symptoms moderated
      indirect associations between the objective neighborhood environment and physical
      activity via the perceived neighborhood environment in older women. We analyzed
      data on 60,133 women (mean age = 73.1 +/- 6.7 years) in the U.S. Nurses' Health
      Study cohort who completed the 2008 questionnaire. Self-reported measures
      included the Geriatric Depression Scale, perceived presence of recreational
      facilities, retail destinations, sidewalks, and crime, and participation in
      recreational physical activity and neighborhood walking. We created an objective
      walkability index by summing z-scores of intersection and facility counts within
      1200-meter residential network buffers and census tract-level population density.
      We used multiple regression with bootstrap-generated 95% bias-corrected
      confidence intervals (BC CIs) to test for mediation and moderated mediation.
      Objective walkability was associated with 1.99 times greater odds of neighborhood
      walking (95% BC CI = 1.92, 2.06) and 1.38 times greater odds of meeting physical
      activity recommendations (95% BC CI = 1.34, 1.43) via the perceived neighborhood
      environment. These indirect associations were weaker among women with higher
      depressive symptom scores. Positive associations between objective neighborhood
      walkability and physical activities such as walking among older women may be
      strengthened with a reduction in their depressive symptoms.

PMID- 30092317
TI  - Role of estrogens in fish immunity with special emphasis on GPER1.
AB  - It is well accepted that estrogens, the primary female sex hormones, play a key
      role in modulating different aspects of the immune response. Moreover, estrogens
      have been linked with the sexual dimorphism observed in some immune disorders,
      such as chronic inflammatory and autoimmune diseases. Nevertheless, their effects
      are often controversial and depend on several factors, such as the pool of
      estrogen receptors (ERs) involved in the response. Their classical mode of action
      is through nuclear ERs, which act as transcription factors, promoting the
      regulation of target genes. However, it has long been noted that some of the
      estrogen-mediated effects cannot be explained by these classical receptors, since
      they are rapid and mediated by non-genomic signaling pathways. Hence, the
      interest in membrane ERs, especially in G protein-coupled estrogen receptor 1
      (GPER1), has grown in recent years. Although the presence of nuclear ERs, and ER
      signaling, in immune cells in mammals and fish has been well documented,
      information on membrane ERs is much scarcer. In this context, the present
      manuscript aims to review our knowledge concerning the effect of estrogens on
      fish immunity, with special emphasis on GPER1. For example, the numerous tools
      developed over recent years allowed us to report for the first time that the
      regulation of fish granulocyte functions by estrogens through GPER1 predates the
      split of fish and tetrapods more than 450 million years ago, pointing to the
      relevance of estrogens as modulators of the immune responses, and the pivotal
      role of GPER1 in immunity.

PMID- 30092316
TI  - Evolutional conservation of molecular structure and antiviral function of a type
      I interferon, IFN-kappa, in poultry.
AB  - IFN-kappa (IFN-kappa) is a type I IFN expressed by keratinocytes, monocytes and
      dendritic cells with important roles during the innate immune response period.
      This research was conducted to elaborate the evolution and characteristics of IFN
      kappa in poultry. Chicken IFN-kappa is located on the sex-determining Z
      chromosome, which is greatly different from mammals. Poultry IFN-kappa cluster
      together in a species-specific manner through positive selection pressure and
      share only 19-33% homology with mammalian IFN-kappa and poultry other type I IFN.
      Both chicken and duck IFN-kappa was constitutively expressed in spleen, skin,
      lung, and peripheral blood mononuclear cells (PBMC), as well as being
      significantly induced after treatment with virus in PBMC. Biologically, poultry
      IFN-kappa has antiviral activity against VSV in chicken embryonic fibroblasts and
      duck embryonic fibroblasts (CEF and DEF) cells, and induces the expression of IFN
      stimulated genes (ISGs). After treatment with JAK1 inhibitor, the ISGs expression
      can be down-regulated. Overall, our research on poultry IFN-kappa not only
      enriches the knowledge about IFN-kappa but also facilitates further research on
      the role of type I IFNs in antiviral defense responses in poultry.

PMID- 30092318
TI  - Two host gut-derived lactic acid bacteria activate the proPO system and increase
      resistance to an AHPND-causing strain of Vibrio parahaemolyticus in the shrimp
      Litopenaeus vannamei.
AB  - Lactic acid bacteria (LAB) are group of beneficial bacteria that have been
      proposed as relevant probiotics with immunomodulatory functions. In this study,
      we initially isolated and identified host-derived LAB from the gut of the Pacific
      white shrimp Litopenaeus vannamei. Analysis of the bacterial 16S rRNA gene
      sequence revealed two candidate LAB, the Lactobacillus plantarum strain SGLAB01
      and the Lactococcus lactis strain SGLAB02, which exhibited 99% identity to the L.
      plantarum strain LB1-2 and the L. lactis strain R-53658, which were isolated from
      bee gut, respectively. The two LAB displayed antimicrobial activities against
      gram-positive and gram-negative bacteria, including the virulent acute
      hepatopancreatic necrosis disease (AHPND)-causing strain of Vibrio
      parahaemolyticus (VPAHPND). Viable colony count and SEM analysis showed that the
      two candidate LAB, administered via oral route as feed supplement, could reside
      and adhere in the shrimp gut. Double-stranded RNA-mediated gene silencing of
      LvproPO1 and LvproPO2 revealed a significant role of two LvproPOs in the proPO
      system as well as in the immune response against VPAHPND infection in L. vannamei
      shrimp. The effect of LAB supplementation on modulation of the shrimp proPO
      system was investigated in vivo, and the results showed that administration of
      the two candidate LAB significantly increased hemolymph PO activity, the relative
      mRNA expression of LvproPO1 and LvproPO2, and resistance to VPAHPND infection.
      These findings suggest that administration of L. plantarum and L. lactis could
      modulate the immune system and increase shrimp resistance to VPAHPND infection
      presumably via upregulation of the two LvproPO transcripts.

PMID- 30092319
TI  - Shingles and pneumonia and risk of cutaneous basal and squamous cell carcinoma.

PMID- 30092321
TI  - Comparison of the efficacy and safety of a picosecond alexandrite laser and a Q
      switched alexandrite laser for the treatment of freckles in Chinese patients.

PMID- 30092320
TI  - Response to Authors Concern for Mischaracterization of Referenced Publications.

PMID- 30092322
TI  - Updates in therapeutics for folliculitis decalvans: A systematic review with
      evidence-based analysis.

PMID- 30092323
TI  - Incidence of herpes zoster among patients with hidradenitis suppurativa: A
      retrospective population-based cohort analysis.

PMID- 30092325
TI  - Comprehending prurigo nodularis: Ay, there's the rub.

PMID- 30092324
TI  - Dupilumab does not affect correlates of vaccine-induced immunity: a randomized,
      placebo-controlled trial in adults with moderate-to-severe atopic dermatitis.
AB  - BACKGROUND: The impact of dupilumab, an anti-interleukin (IL)-4Ralpha antibody
      that inhibits IL-4/IL-13 signaling, on vaccine responses in atopic dermatitis
      (AD) patients is unknown. OBJECTIVES: To assess T-cell-dependent and -independent
      humoral responses to tetanus and meningococcal vaccines, IgE seroconversion to
      tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap)
      vaccination, and dupilumab efficacy and safety. METHODS: In a randomized, double
      blinded, placebo-controlled study (NCT02210780), adults with moderate-to-severe
      AD received dupilumab (300 mg) or placebo weekly for 16 weeks, and single doses
      of Tdap and quadrivalent meningococcal polysaccharide vaccines at Week 12.
      Primary endpoint was proportion of patients achieving satisfactory IgG response
      to tetanus toxoid at Week 16. RESULTS: 178 patients completed the study. Similar
      positive responses with dupilumab/placebo to tetanus (83.3%/83.7%) and
      meningococcal polysaccharide (86.7%/87.0%) were achieved. Dupilumab significantly
      decreased total serum IgE; most dupilumab-treated patients were Tdap IgE
      seronegative at Week 32 (62.2%/34.8%; dupilumab/placebo). Dupilumab improved key
      AD efficacy endpoints (P<0.001). Injection-site reactions and conjunctivitis were
      more common with dupilumab; AD exacerbations more frequent with placebo.
      LIMITATION: Patients' prior vaccination status was not available before
      enrollment. CONCLUSIONS: Dupilumab did not affect responses to the vaccines
      studied, significantly decreased IgE, and improved measures of AD severity versus
      placebo, with an acceptable safety profile.

PMID- 30092326
TI  - Dupilumab use in allergic contact dermatitis.

PMID- 30092327
TI  - Immune checkpoint inhibitors and the development of granulomatous reactions.
AB  - Immune checkpoint inhibitors (ICPis) have emerged as a frontline treatment for a
      growing list of malignancies. Disruption of the negative regulatory immune
      checkpoints by ICIs has been associated with many immune-related adverse events
      (irAEs). Granulomatous reactions, such as sarcoidosis-like, granulomatous
      panniculitis, granuloma annulare, and granulomatous dermatitis, are an uncommon,
      but increasingly recognized irAE seen in patients treated with ICIs. The
      frequency and significance of these eruptions, including the question of whether
      they portend treatment responsiveness, remains unclear. Additionally,
      understanding the role of immune checkpoint blockade in these reactions may
      provide mechanistic insight into the relevant signaling pathways involved in
      sarcoidosis and other granulomatous disorders.

PMID- 30092328
TI  - Cutaneous malignant melanoma incidence and mortality trends in Canada: A
      comprehensive population-based study.
AB  - BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) is on the rise in
      many parts of the world. However, there is limited knowledge on the epidemiology
      of CMM in Canada. OBJECTIVE: To conduct a comprehensive population-based study of
      CMM in Canada. METHODS: We examined patient clinical and pathologic
      characteristics as well as the incidence and mortality trends of CMM in Canada
      using 3 independent population-based registries. RESULTS: In total, 72,565
      Canadian patients were given CMM diagnoses during 1992-2010; 47.5% were women.
      Average age at the time of diagnosis was 56.5 years for women and 60.4 years for
      men. We report a steady increase in CMM incidence and mortality rates in both
      sexes. The overall incidence rate of CMM in Canada was 12.29 cases/100,000 person
      years. We also report important differences in the incidence and mortality rates
      between Canadian provinces and territories; the highest incidence of this cancer
      was documented in Nova Scotia and Prince Edward Island. LIMITATIONS: Data on
      race, clinical disease stage, and Breslow depth of CMM was not available.
      CONCLUSION: This study, for the first time, defines the disease burden of CMM in
      Canada and highlights important longitudinal, geographic, and spatial differences
      in the distribution of CMM in this country.

PMID- 30092329
TI  - Mortality in intravascular large B-cell lymphoma: A SEER analysis.

PMID- 30092330
TI  - Association of skin hyperpigmentation disorders with digital ulcers in systemic
      sclerosis: analysis of a cohort of 239 patients.
AB  - BACKGROUND: Skin pigmentation disorders in systemic sclerosis (SSc) have been
      sparsely described in the literature. Nevertheless, they could be a diagnostic
      and/or a severity marker. OBJECTIVES: To assess the association between
      pigmentation disorders and systemic involvement in SSc patients. METHODS: Five
      patterns of skin pigmentation disorders were defined: diffuse hyperpigmentation,
      sun-exposed area hyperpigmentation, head/neck/upper chest hypopigmentation, acral
      hypopigmentation and diffuse hypopigmentation. RESULTS: 239 patients were
      included, eighty-eight (36.8%) patients had skin pigmentation disorders as
      follows: diffuse and sun-exposed hyperpigmentation in 38.6% (n=34) and 27.3%
      (n=24) respectively, face/neck/chest hypopigmentation in 10.2% (n=9), diffuse
      hypopigmentation in 12.5% (n=11) and acral hypopigmentation in 17% (n=15).
      Diffuse hyperpigmentation, was associated with diffuse SSc (p= 0.001), increased
      modified Rodnan's skin score (mRSS) (p= 0.001) and and shorter duration of
      Raynaud (p=0.002) in univariate analysis but not in multivariate analysis.
      Moreover, diffuse hyperpigmentation was associated with digital ulcers (p= 0.005)
      confirmed by multivariate analysis OR 2.96 [1.28-6.89]. LIMITATIONS: This was a
      single-center retrospective study on a cohort of SSc patients. CONCLUSION:
      Screening for skin pigmentation disorders could be useful in the management of
      SSc patients to identify patients with a high risk of developing digital ulcers,
      a symptom of vascular involvement in SSc.

PMID- 30092331
TI  - Psoriasis is not associated with cognition, brain imaging markers and risk of
      dementia: the Rotterdam Study.
AB  - BACKGROUND: Based on increased cardio-metabolic comorbidities, inflammation and
      an overlap in genetics with Alzheimer's disease, psoriasis patients may be at
      risk for cognitive dysfunction and dementia. OBJECTIVE: To compare cognition,
      magnetic resonance imaging (MRI)-markers and dementia risk in psoriasis and non
      psoriasis participants in the population-based Rotterdam Study. METHODS: We
      identified 318 psoriatic and 9678 non-psoriatic participants (mean age: 66.1
      years, 58% women). The association of psoriasis with cognitive function, mild
      cognitive impairment (MCI) and MRI-markers of brain damage was examined by linear
      and logistic regression. Dementia risk was calculated using Cox regression.
      Models were adjusted for age, gender, education and cardio-vascular risk factors.
      RESULTS: Cognitive test scores and volumetric, microstructural, focal measures on
      brain MRI did not differ between psoriasis (28% systemic/UV treatment) and non
      psoriasis participants and psoriasis was not associated with MCI (adjusted odd
      ratio 0.87, (95% Confidence Interval (CI): 0.53-1.43)). During 115.000 person
      years of follow-up, 810 incident dementia cases (15 among psoriasis patients)
      occurred. After adjusting for confounders, psoriasis was associated with a lower
      risk of developing dementia (adjusted hazard ratio 0.50, (95% CI: 0.28-0.91)).
      LIMITATIONS: Limited dementia cases among psoriasis patients. CONCLUSIONS: In
      this population-based study, psoriasis was not associated with preclinical
      markers or higher dementia risk.

PMID- 30092332
TI  - Association of alopecia areata with hospitalization for mental health disorders
      in US adults.
AB  - Patients with alopecia areata have multiple risk factors for mental health
      disorders, including psychological distress and impaired quality of life.
      Alopecia areata was associated with increased mental health disorders and
      hospitalization primarily for a mental health disorders. Alopecia areata patients
      require close monitoring for mental health disorders.

PMID- 30092333
TI  - Effectiveness of Rotating Shield Brachytherapy for Prostate Cancer Dose
      Escalation and Urethral Sparing.
AB  - PURPOSE: To compare single-fraction 153Gd-based rotating shield brachytherapy
      (RSBT) for prostate cancer with conventional 192Ir-based high-dose-rate
      brachytherapy (HDR-BT) in a planning study that radiobiologically accounts for
      dose rate and relative biological effectiveness. RSBT was used for planning
      target volume (PTV) dose escalation without increasing urethral dose for
      monotherapy, or for urethral sparing without decreasing PTV dose as a boost to
      external beam radiation therapy. METHODS AND MATERIALS: Twenty-six patients were
      studied. PTV doses were expressed as equivalent dose delivered in 2 Gy fractions
      (EQD2), accounting for relative biological effectiveness (1.00 for 192Ir and 1.15
      for 153Gd), dose protraction (114-minute repair half-time), and tumor dose
      response (alpha/beta of 3.41 Gy). HDR-BT dose was prescribed such that 90% of the
      PTV received 110% of the prescription dose of 19 Gy for dose escalation and 15 Gy
      for urethral sparing, corresponding to EQD290% values (minimum EQD2 to the
      hottest 90% of the PTV) of 93.9 GyEQD2 and 60.7 GyEQD2, respectively. Twenty
      90.95 GBq 153Gd RSBT sources and one 370 GBq 192Ir HDR-BT source were modeled.
      RESULTS: For dose escalation with fresh sources, RSBT increased PTV EQD290% by
      42.5% +/- 8.4% (average +/- standard deviation) without increasing urethral D10%,
      with treatment times of 216.8 +/- 28.9 minutes versus 15.1 +/- 2.1 minutes. After
      1 half-life (240.4 days for 153Gd and 73.8 days for 192Ir), EQD290% increased
      20.5% +/- 9.1%. For urethral sparing with fresh sources, RSBT decreased urethral
      D10% by 26.0% +/- 3.4% without decreasing PTV EQD290%, with treatment times of
      133.6 +/- 16.5 minutes versus 12.0 +/- 1.7 minutes. After 1 half-life, urethral
      D10% decreased 20.2% +/- 4.8%. CONCLUSIONS: RSBT can increase PTV EQD90% or
      decrease urethral D10% relative to HDR-BT at the cost of increased treatment
      time. Source aging reduces RSBT benefit, but RSBT remains theoretically superior
      to HDR-BT by >20% after 1 half-life has elapsed.

PMID- 30092334
TI  - Dimethyl Sulfoxide Prevents Radiation-induced Oral Mucositis through Facilitating
      DNA Double-strand Break Repair in Epithelial Stem Cell.
AB  - PURPOSE: Oral mucositis is one of the most prevalent side effects in patients
      undergoing radiotherapy for head and neck cancers. Current therapeutic agents
      such as palifermin (rhKGF) and amifostine do not efficiently or fully prevent
      mucositis. Dimethyl sulfoxide (DMSO), a free-radical scavenger, has shown
      therapeutic benefits in many preclinical and clinical studies. This study aimed
      to investigate the efficacy of DMSO in a clinically relevant mouse model of
      acute, radiation-induced oral mucositis. METHODS AND MATERIALS: Oral mucositis
      was exerted by a high single and fractioned irradiation of the head and neck area
      in C57BL/6J mice, and the effects of DMSO (by intraperitoneal injection) were
      assessed by macroscopic and histopathological examination. Epithelial stem and
      progenitor cells were analyzed by immunohistochemical staining of p63 and ki67,
      and DNA double-strand breaks (DSBs) was visualized by immunofluorescence
      detection of gamma-H2AX. Tumor xenograft was obtained using CAL-27 cells.
      RESULTS: Pretreatment with DMSO protected the oral mucosa from severe acute
      radiation injury, reduced the extent of radiation induced weight loss, and had no
      significant effects on tumor weight in irradiated or non-irradiated xenograft
      mice. Furthermore, the efficacy of DMSO was superior to that of rhKGF and
      amifostine. DMSO treatment prevented the loss of proliferative lingual epithelial
      stem and progenitor cells upon irradiation. More interestingly, the average
      levels of gamma-H2AX foci were significantly decreased in p63-positive epithelial
      stem cells at 6h, but not at 2h after irradiation, indicating that DMSO
      facilitated DNA DSBs repair rather than suppressing the indirect action of
      irradiation. CONCLUSION: DMSO prevents the loss of proliferative lingual
      epithelial stem and progenitor cells upon irradiation by facilitating of DNA DSBs
      repair, thereby protecting from radiation-induced mucositis without tumor
      protection. Given its high efficacy and low toxicity, DMSO could be a potential
      treatment option to prevent radiation-induced oral mucositis.

PMID- 30092335
TI  - Development of a Ready-to-Use Graphical Tool Based on Artificial Neural Network
      Classification: Application for the Prediction of Late Fecal Incontinence After
      Prostate Cancer Radiation Therapy.
AB  - PURPOSE: This study was designed to apply artificial neural network (ANN)
      classification methods for the prediction of late fecal incontinence (LFI) after
      high-dose prostate cancer radiation therapy and to develop a ready-to-use
      graphical tool. MATERIALS AND METHODS: In this study, 598 men recruited in 2
      national multicenter trials were analyzed. Information was recorded on
      comorbidity, previous abdominal surgery, use of drugs, and dose distribution.
      Fecal incontinence was prospectively evaluated through self-reported
      questionnaires. To develop the ANN, the study population was randomly split into
      training (n = 300), validation (n = 149), and test (n = 149) sets. Mean grade of
      longitudinal LFI (ie, expressed as the average incontinence grade over the first
      3 years after radiation therapy) >=1 was considered the endpoint. A suitable
      subset of variables able to better predict LFI was selected by simulating 100,000
      ANN configurations. The search for the definitive ANN was then performed by
      varying the number of inputs and hidden neurons from 4 to 5 and from 1 to 9,
      respectively. A final classification model was established as the average of the
      best 5 among 500 ANNs with the same architecture. An ANN-based graphical method
      to compute LFI prediction was developed to include one continuous and n
      dichotomous variables. RESULTS: An ANN architecture was selected, with 5 input
      variables (mean dose, previous abdominal surgery, use of anticoagulants, use of
      antihypertensive drugs, and use of neoadjuvant and adjuvant hormone therapy) and
      4 hidden neurons. The developed classification model correctly identified
      patients with LFI with 80.8% sensitivity and 63.7% +/- 1.0% specificity and an
      area under the curve of 0.78. The developed graphical tool may efficiently
      classify patients in low, intermediate, and high LFI risk classes. CONCLUSIONS:
      An ANN-based model was developed to predict LFI. The model was translated in a
      ready-to-use graphical tool for LFI risk classification, with direct
      interpretation of the role of the predictors.

PMID- 30092336
TI  - Radiation-Induced Cerebral Microbleeds in Pediatric Patients With Brain Tumors
      Treated With Proton Radiation Therapy.
AB  - PURPOSE: Proton beam radiation therapy (PBT) has been increasingly used to treat
      pediatric brain tumors; however, limited information exists regarding radiation
      induced cerebral microbleeds (CMBs) among these patients. The purpose of this
      study was to evaluate the incidence, risk factors, and imaging appearance of CMBs
      in pediatric patients with brain tumors treated with PBT. MATERIALS AND METHODS:
      A retrospective study was performed of 100 pediatric patients with primary brain
      tumors treated with PBT. CMBs were diagnosed by examination of serial magnetic
      resonance imaging scans, including susceptibility-weighted imaging. Radiation
      therapy plans were analyzed to determine doses to individual CMBs. Clinical
      records were used to determine risk factors associated with the development of
      CMBs in these patients. RESULTS: The mean age at time of PBT was 8.1 years. The
      median follow-up duration was 57 months. The median time to development of CMBs
      was 8 months (mean, 11 months; range, 3-28 months). The percentage of patients
      with CMBs was 43%, 66%, 80%, 81%, 83%, and 81% at 1 year, 2 years, 3 years, 4
      years, 5 years, and >5 years from completion of proton radiation therapy. Most of
      the CMBs (87%) were found in areas of brain exposed to >=30 Gy. Risk factors
      included maximum radiation therapy dose (P = .001), percentage and volume of
      brain exposed to >=30 Gy (P = .0004, P = .0005), and patient age at time of PBT
      (P = .0004). Chemotherapy was not a significant risk factor (P = .35). No CMBs
      required surgical intervention. CONCLUSIONS: CMBs develop in a high percentage of
      pediatric patients with brain tumors treated with proton radiation therapy within
      the first few years after treatment. Significant risk factors for development of
      CMBs include younger age at time of PBT, higher maximum radiation therapy dose,
      and higher percentage and volume of brain exposed to >=30 Gy. These findings
      demonstrate similarities with CMBs that develop in pediatric patients with brain
      tumor treated with photon radiation therapy.

PMID- 30092337
TI  - Bone marrow mesenchymal stromal cells attenuate liver allograft rejection may via
      upregulation PD-L1 expression through downregulation of miR-17-5p.
AB  - Studies have reported that bone marrow mesenchymal stem cells (BMSCs) play an
      important role in immune regulation after organ transplantation. Some of the BMSC
      mediated regulatory mechanisms are related to PD-L1 expression. However, the
      regulatory mechanism of PD-L1 expression is not fully understood. In this
      experiment, we confirmed the regulatory role of BMSCs in the rejection of liver
      transplantation and explored the possible mechanism by which PD-L1 expression is
      regulated in BMSCs. An orthotopic liver transplantation model in rats was
      established based on the "double-cuff technique". Third-generation BMSCs were
      injected into the rejection model rats via portal vein. At the same time, sera
      were obtained from rats in the allograft, isograft and sham-operated groups. The
      sera from these groups were separately added to BMSCs complete medium to
      partially mimic the in vivo environment in which BMSCs are exposed. After
      predicting and analysing microRNAs that regulate PD-L1 expression, we examined
      the microRNA and PD-L1 expression in BMSCs of the three groups cultured in the
      conditioned media. Moreover, a luciferase reporter assay was used to confirm the
      interaction between PD-L1 and microRNA. The study found that the liver function
      and liver graft histopathology of the BMSC-treated group were better than those
      of the allograft group. The Kaplan-Meier survival curve analysis showed that the
      median survival time (MST) of the BMSC-treated group was longer than that of the
      allograft group. Bioinformatics prediction and analysis showed that miR-17-5p is
      highly likely to regulate PD-L1. Compared with the other two groups of cells,
      BMSCs cultured with serum from allograft models showed higher PD-L1 expression,
      but lower miR-17-5p expression. Pearson correlation analysis showed that miR-17
      5p and PD-L1 expression was negatively correlated, and further luciferase
      reporter assays confirmed that miR-17-5p interacted directly with the 3'
      untranslated region (UTR) of PD-L1 mRNA. The results of this study demonstrate
      that BMSCs can attenuate liver allograft rejection and provide us with the idea
      that BMSCs may further upregulate PD-L1 expression by downregulating miR-17-5p
      expression, thereby attenuating liver allograft rejection.

PMID- 30092339
TI  - Representational fluidity in embodied (artificial) cognition.
AB  - Theories of embodied cognition agree that the body plays some role in human
      cognition, but disagree on the precise nature of this role. While it is (together
      with the environment) fundamentally engrained in the so-called 4E (or multi-E)
      cognition stance, there also exists interpretations wherein the body is merely an
      input/output interface for cognitive processes that are entirely computational.
      In the present paper, we show that even if one takes such a strong
      computationalist position, the role of the body must be more than an interface to
      the world. To achieve human cognition, the computational mechanisms of a
      cognitive agent must be capable not only of appropriate reasoning over a given
      set of symbolic representations; they must in addition be capable of updating the
      representational framework itself (leading to the titular representational
      fluidity). We demonstrate this by considering the necessary properties that an
      artificial agent with these abilities need to possess. The core of the argument
      is that these updates must be falsifiable in the Popperian sense while
      simultaneously directing representational shifts in a direction that benefits the
      agent. We show that this is achieved by the progressive, bottom-up symbolic
      abstraction of low-level sensorimotor connections followed by top-down
      instantiation of testable perception-action hypotheses. We then discuss the
      fundamental limits of this representational updating capacity, concluding that
      only fully embodied learners exhibiting such a priori perception-action linkages
      are able to sufficiently ground spontaneously-generated symbolic representations
      and exhibit the full range of human cognitive capabilities. The present paper
      therefore has consequences both for the theoretical understanding of human
      cognition, and for the design of autonomous artificial agents.

PMID- 30092338
TI  - B cell phenotypes in baboons with pig artery patch grafts receiving conventional
      immunosuppressive therapy.
AB  - BACKGROUND: In the pig-to-baboon artery patch model with no immunosuppressive
      therapy, a graft from an alpha1,3-galactosyltransferase gene-knockout (GTKO) pig
      elicits a significant anti-nonGal IgG response, indicating sensitization to the
      graft. A costimulation blockade-based regimen, e.g., anti-CD154mAb or anti
      CD40mAb, prevents sensitization. However, neither of these agents is currently
      FDA-approved. The aim of the present study was to determine the efficacy of FDA
      approved agents on the T and B cell responses. METHODS: Artery patch
      xenotransplantation in baboons was carried out using GTKO/CD46 pigs with (n = 2)
      or without (n = 1) the mutant transgene for CIITA-knockdown. Immunosuppressive
      therapy consisted of induction with ATG and anti-CD20mAb, and maintenance with
      different combinations of CTLA4-Ig, tacrolimus, and rapamycin. In addition, all 3
      baboons received daily corticosteroids, the IL-6R blocker, tocilizumab, at
      regular intervals, and the TNF-alpha blocker, etanercept, for the first 2 weeks.
      Recipient blood was monitored for anti-nonGal antibody levels by flow cytometry
      (using GTKO/CD46 pig aortic endothelial cells), and mixed lymphocyte reaction
      (MLR). CD22+B cell profiles (naive [IgD+/CD27-], non-switched memory
      [IgD+/CD27+], and switched memory [IgD-/CD27+] B cell subsets) were measured by
      flow cytometry. At 6 months, the baboons were euthanized and the grafts were
      examined histologically. RESULTS: No elicited anti-pig antibodies developed in
      any baboon. The frequency of naive memory B cells increased significantly (from
      34% to 90%, p = 0.0015), but there was a significant decrease in switched memory
      B cells (from 17% to 0.5%, p = 0.015). MLR showed no increase in the
      proliferative T cell response in those baboons that had received CTLA4-Ig (n =
      2). Histological examination showed few or no features of rejection in any graft.
      CONCLUSIONS: The data suggest that immunosuppressive therapy with only FDA
      approved agents may be adequate to prevent an adaptive immune response to a
      genetically-engineered pig graft, particularly if CTLA4-Ig is included in the
      regimen, in part because the development of donor-specific memory B cells is
      inhibited.

PMID- 30092340
TI  - The internal transcribed spacer 2 of Jenufa (Chlorophyta, Chlorophyceae) is
      extraordinarily long: A hypothesis.
AB  - Aided by a host of bioinformatics tools, primary and secondary structural
      analyses of the internal transcribed spacer 2 (ITS2) from the eukaryotic
      ribosomal RNA repeat have a long and enviable record of service to diversity
      studies of fungi, plants and protists. Automation of annotation, secondary
      structure estimation and sequence alignment have become routine for the vast
      majority of ITS2 sequences. Challenges to the bioinformatics pipeline for ITS2
      analysis generally arise in cases where the sequence length lies well outside the
      norm. These sequences generally defy protocols for annotation and secondary
      structure prediction. The long ITS2 sequences (ca. 600 nucleotides) from the
      green alga, Jenufa, offered an opportunity to explore this problem. Custom BLAST
      parameters revealed the presence of 4-helix structures (200-250 nucleotides)
      embedded in the 5' portion of several long ITS2 sequences of Jenufa. Of special
      note is the ITS2 sequence of J. lobulosa where a 4-helix structure was obtained
      for both the embedded ITS2 and for the complete sequence. Phylogenetic analysis
      of these typically-sized sequences resolved Golenkinia longispicula as the sister
      to Jenufa. Our observations indicate that other long ITS2 sequences should be
      examined for evidence of expansion or duplication. In addition, if the embedded
      ITS2 sequences are functional, then ribogenesis is almost certainly more diverse
      than is already apparent from studies of humans and yeast.

PMID- 30092341
TI  - Expression profiles of MicroRNAs from multiple lumbar spine in sheep.
AB  - The formation of the spine is a critical stage of mammalian development. The
      increase of the number of individual axons affects its performance, especially in
      meat production. To understand the role of miRNAs in sheep vertebrae development,
      the purpose of this article is to screen candidate microRNAs (miRNAs) associated
      with sheep spine development. MicroRNAs (miRNAs) are a rich family of small
      regulatory RNAs that negatively regulate gene expression at the post
      transcriptional level. In this study, we used high-throughput sequencing
      techniques to analyze the microRNAs (miRNAs) expression profiles of L6 (6 lumbar
      vertebrae) and L7 (7 lumbar vertebrae) in sheep. A total number of 223 miRNAs
      were detected in the two libraries, and a total of 150 and 148 conserved miRNAs
      were obtained in L6 and L7, respectively. A total of 5 miRNAs expression
      differences in L6 compared to L7 (P < 0.05). Of the five obviously differently
      expressed miRNAs, four miRNAs were down-regulated in the L6 of sheep, and one was
      up-regulated. In order to further explore the functions of these miRNAs, we
      predicted the target genes of these differently expressed miRNAs, and obtained
      1298 target genes. At the same time, NDRG2 gene, targeted by novel miR-391, which
      possible plays an important role in the development of the spine. Linkage
      integration analysis method was used to construct the interaction network of
      spinal-associated miRNA and its hypothesized target. In summary, this study
      provides valuable resources for the transcriptome of multiple vertebral traits in
      sheep.

PMID- 30092342
TI  - Induction of miR-15a expression by tripterygium glycosides caused premature
      ovarian failure by suppressing the Hippo-YAP/TAZ signaling effector Lats1.
AB  - Tripterygium glycosides (TGs) are chemotherapeutic drugs and immunosuppressant
      agents for the treatment of cancer and autoimmune diseases. We have previously
      reported that TGs induces premature ovarian failure (POF) by inducing
      cytotoxicity in ovarian granulosa cells (OGCs). Hence, we report that TGs
      suppress the expression of the Hippo-YAP/TAZ pathway in murine OGCs in vitro and
      in vivo. We found that the expressions of miR-181b, miR-15a, and miR-30d, were
      elevated significantly in the POF. Luciferase reporter assays confirmed that miR
      15a targets Lats1 through a miR-15a binding site in the Lats1 3'UTR.
      Overexpression of miR-15a in mOGCs not only inhibited proliferation and growth of
      mOGCs, but also induced aging of mOGCs. Western blot and qPCR analysis indicated
      that miR-15a suppresses the expression of the Hippo-YAP/TAZ pathway in mOGCs.
      When the exogenous miR-15a was expressed on mouse OGCs, it could elevate the
      cytotoxicity effect of TG on mOGCs. We conclude that tripterygium glycosides
      promote cytotoxicity, senescence, and apoptosis in ovarian granulosa cells by
      inducing endogenous miR-15a expression and inhibiting the Hippo-YAP/TAZ pathway.

PMID- 30092343
TI  - Vitamin D Receptor polymorphisms and risk of enveloped virus infection: A meta
      analysis.
AB  - INTRODUCTION: Vitamin-D plays a role regulating the immune response against to
      viral infection. In this sense, vitamin-D deficiency may confer increased
      susceptibility to enveloped virus infection such as HIV, Hepatitis, Dengue and
      Respiratory Syncytial virus infection, among others. Vitamin D activity is
      mediated by its receptor (VDR), which acts as a transcription factor modulating
      the expression of genes triggering the response against viruses. To date, six
      major VDR polymorphisms (Cdx, A1012G, FokI, BsmI, ApaI and TaqI) have been
      studied in the context of viral infection susceptibility. Reported studies show
      controversial results probably due to statistical lack of power and population
      genetic differences. AIMS: To do a systematic review of the published data and to
      perform a meta-analysis examining the role of six VDR polymorphisms on infection
      susceptibility to enveloped virus. RESULTS: From all markers and virus considered
      an association of FokI polymorphism with RSV infection emerges as significant.
      The worldwide distribution of risk T-allele reveals a lower prevalence in African
      populations that runs parallel with the relative lower incidence of RSV
      associated severe ALRI in children <1 year described in African samples.
      CONCLUSION: The results disclose FokI polymorphism as a relevant variant
      capturing the association of VDR polymorphisms with viral infection.

PMID- 30092345
TI  - Comparative transcriptomics of limb regeneration: Identification of conserved
      expression changes among three species of Ambystoma.
AB  - Transcriptome studies are revealing the complex gene expression basis of limb
      regeneration in the primary salamander model - Ambystoma mexicanum (axolotl). To
      better understand this complexity, there is need to extend analyses to additional
      salamander species. Using microarray and RNA-Seq, we performed a comparative
      transcriptomic study using A. mexicanum and two other ambystomatid salamanders:
      A. andersoni, and A. maculatum. Salamanders were administered forelimb
      amputations and RNA was isolated and analyzed to identify 405 non-redundant genes
      that were commonly, differentially expressed 24 h post amputation. Many of the
      upregulated genes are predicted to function in wound healing and developmental
      processes, while many of the downregulated genes are typically expressed in
      muscle. The conserved transcriptional changes identified in this study provide a
      high-confidence dataset for identifying factors that simultaneous orchestrate
      wound healing and regeneration processes in response to injury, and more
      generally for identifying genes that are essential for salamander limb
      regeneration.

PMID- 30092344
TI  - A novel cryptic and theta type plasmid (pHIG22) from Thermus scodotuctus sp. K6.
AB  - A cryptic plasmid pHIG22 from Thermus scotoductus sp. K6, an isolate from the
      Alangullu Hot Spring (Aydin, Turkey), was sequenced and characterized. The pHIG22
      plasmid is a multicopy, double stranded and 2222 bp circular molecule with 62.78%
      GC content, which shows a characteristical nucleotide sequence without any
      homology to other known plasmids. Five open reading frames were predicted based
      on the nucleotide sequence analysis. The deduced amino acid sequence of all
      predicted ORFs didn't show any similarity with any known proteins. Three
      palindroms were detected and two promoter sequences were predicted in both
      strands. With electron microscopy (TEM) analysis, the replication intermediates
      were seen as typical Q-shaped molecules that committing pHIG22 replicates via the
      Theta replication mechanism. A 2012 bp region among 387 and 614 bp of pHIG22 was
      determined as minimal replicon which carries the elements necessary for plasmid
      replication and ori region. Furthermore, quantitative real-time PCR showed that
      the relative copy number of pHIG22 was estimated to be 148.2 +/- 4.7 copies per
      chromosome equivalent. The new Theta type plasmid would be useful and beneficial
      to build vectors for cloning of thermophilic genes and in vivo protein
      engineering.

PMID- 30092346
TI  - Preparation of pharmaceutical cocrystal formulations via melt mixing technique: A
      thermodynamic perspective.
AB  - The aim of the present study was to evaluate the thermodynamic properties of in
      situ formation of cocrystal formulations by the melt-mixing method. Specifically,
      the thermodynamic mixing behaviour of carbamazepine-nicotinamide and ibuprofen
      nicotinamide cocrystals prepared with the aid of Soluplus(r) (SOL) were evaluated
      using thermodynamic lattice-based solution theories. Thermodynamic miscibility of
      both cocrystals with SOL was predicted by calculating Gibb's free energy based on
      the Flory-Huggins (FH) interaction parameter (chi), while the activity
      coefficient of cocrystals estimated with the aid of solid-liquid equilibrium
      equation and FH lattice theory, showed good thermodynamic miscibility of the
      components at elevated temperatures used normally during melt-mixing based
      processes. Complete phase transition diagrams constructed with the aid of DSC
      measurements and FH solution theory, suggested the existence of two transition
      zones: (1) a stable cocrystal zone, located at the right-hand-side of the
      spinodal phase separation curve, where stable cocrystals are prepared and (2) an
      unstable cocrystal zone, located at the left-hand-side of the spinodal curve up
      to liquidus, where the matrixforming polymer sets a kinetic barrier to
      recrystallization and hence, a barrier to the formation of cocrystals. The
      validity of the suggested thermodynamic phase transition zones was experimentally
      verified by ATR-FTIR and hot-stage polarized light microscopy.

PMID- 30092348
TI  - Prediction of individualized task activation in sensory modality-selective
      frontal cortex with 'connectome fingerprinting'.
AB  - The human cerebral cortex is estimated to comprise 200-300 distinct functional
      regions per hemisphere. Identification of the precise anatomical location of an
      individual's unique set of functional regions is a challenge for neuroscience
      that has broad scientific and clinical utility. Recent studies have demonstrated
      the existence of four interleaved regions in lateral frontal cortex (LFC) that
      are part of broader visual attention and auditory attention networks (Michalka et
      al., 2015; Noyce et al., 2017; Tobyne et al., 2017). Due to a large degree of
      inter-subject anatomical variability, identification of these regions depends
      critically on within-subject analyses. Here, we demonstrate that, for both sexes,
      an individual's unique pattern of resting-state functional connectivity can
      accurately identify their specific pattern of visual- and auditory-selective
      working memory and attention task activation in lateral frontal cortex (LFC)
      using "connectome fingerprinting." Building on prior techniques (Saygin et al.,
      2011; Osher et al., 2016; Tavor et al., 2016; Smittenaar et al., 2017; Wang et
      al., 2017; Parker Jones et al., 2017), we demonstrate here that connectome
      fingerprint predictions are far more accurate than group-average predictions and
      match the accuracy of within-subject task-based functional localization, while
      requiring less data. These findings are robust across brain parcellations and are
      improved with penalized regression methods. Because resting-state data can be
      easily and rapidly collected, these results have broad implications for both
      clinical and research investigations of frontal lobe function. Our findings also
      provide a set of recommendations for future research.

PMID- 30092347
TI  - Free viewing of talking faces reveals mouth and eye preferring regions of the
      human superior temporal sulcus.
AB  - During face-to-face communication, the mouth of the talker is informative about
      speech content, while the eyes of the talker convey other information, such as
      gaze location. Viewers most often fixate either the mouth or the eyes of the
      talker's face, presumably allowing them to sample these different sources of
      information. To study the neural correlates of this process, healthy humans
      freely viewed talking faces while brain activity was measured with BOLD fMRI and
      eye movements were recorded with a video-based eye tracker. Post hoc trial
      sorting was used to divide the data into trials in which participants fixated the
      mouth of the talker and trials in which they fixated the eyes. Although the
      audiovisual stimulus was identical, the two trials types evoked differing
      responses in subregions of the posterior superior temporal sulcus (pSTS). The
      anterior pSTS preferred trials in which participants fixated the mouth of the
      talker while the posterior pSTS preferred fixations on the eye of the talker. A
      second fMRI experiment demonstrated that anterior pSTS responded more strongly to
      auditory and audiovisual speech than posterior pSTS eye-preferring regions. These
      results provide evidence for functional specialization within the pSTS under more
      realistic viewing and stimulus conditions than in previous neuroimaging studies.

PMID- 30092349
TI  - An elastase activity reporter for Electronic Paramagnetic Resonance (EPR) and
      Overhauser-enhanced Magnetic Resonance Imaging (OMRI) as a line-shifting
      nitroxide.
AB  - Pulmonary inflammatory diseases are a major burden worldwide. They have in common
      an influx of neutrophils. Neutrophils secrete unchecked proteases at inflammation
      sites consequently leading to a protease/inhibitor imbalance. Among these
      proteases, neutrophil elastase is responsible for the degradation of the lung
      structure via elastin fragmentation. Therefore, monitoring the protease/inhibitor
      status in lungs non-invasively would be an important diagnostic tool. Herein we
      present the synthesis of a MeO-Suc-(Ala)2-Pro-Val-nitroxide, a line-shifting
      elastase activity probe suitable for Electron Paramagnetic Resonance spectroscopy
      (EPR) and Overhauser-enhanced Magnetic Resonance Imaging (OMRI). It is a fast and
      sensitive neutrophil elastase substrate with Km = 15 +/- 2.9 uM, kcat/Km =
      930,000 s-1 M-1 and Km = 25 +/- 5.4 uM, kcat/Km = 640,000 s-1 M-1 for the R and S
      isomers, respectively. These properties are suitable to detect accurately
      concentrations of neutrophil elastase as low as 1 nM. The substrate was assessed
      with broncho-alveolar lavages samples derived from a mouse model of Pseudomonas
      pneumonia. Using EPR spectroscopy we observed a clear-cut difference between wild
      type animals and animals deficient in neutrophil elastase or deprived of
      neutrophil Elastase, Cathepsin G and Proteinase 3 or non-infected animals. These
      results provide new preclinical ex vivo and in vivo diagnostic methods. They can
      lead to clinical methods to promote in time lung protection.

PMID- 30092350
TI  - Handling heme: The mechanisms underlying the movement of heme within and between
      cells.
AB  - Heme is an essential cofactor and signaling molecule required for virtually all
      aerobic life. However, excess heme is cytotoxic. Therefore, heme must be safely
      transported and trafficked from the site of synthesis in the mitochondria or
      uptake at the cell surface, to hemoproteins in most subcellular compartments.
      While heme synthesis and degradation are relatively well characterized, little is
      known about how heme is trafficked and transported throughout the cell. Herein,
      we review eukaryotic heme transport, trafficking, and mobilization, with a focus
      on factors that regulate bioavailable heme. We also highlight the role of
      gasotransmitters and small molecules in heme mobilization and bioavailability,
      and heme trafficking at the host-pathogen interface.

PMID- 30092351
TI  - Analyses of nucleotide, synonymous codon and amino acid usages at gene levels of
      Brucella melitensis strain QY1.
AB  - Brucella melitensis is the causative pathogen of the zoonotic disease brucellosis
      in China. This work focused on analyses of genetic features represented by
      nucleotide, synonymous codon and amino acid usages at gene levels of B.
      melitensis strain QY1 isolated from China. Although nucleotide usage biases at
      different codon positions all work on synonymous codon usage bias, nucleotide
      usage biases at the 1st and 3rd positions play more important roles in codon
      usages. Mutation pressure caused by nucleotide composition constraint influences
      the formation of over-representative synonymous codons, but neighboring
      nucleotides surrounding a codon strongly influence synonymous codon usage bias
      for B. melitensis strain QY1. There is significant correlation between amino acid
      usage bias and hydropathicity of proteins for B. melitensis strain QY1. Compared
      with different Brucella species about synonymous codon usage patterns, synonymous
      codon usages are not obviously influenced by hosts. Due to nucleotide usage bias
      at the 1st codon position influencing synonymous codon and amino acid usages,
      good interactions among nucleotide, synonymous codon and amino acid usages exist
      in the evolutionary process of B. melitensis.

PMID- 30092352
TI  - Inhibition of C5a prevents IL-1beta-induced alternations in rat synoviocytes in
      vitro.
AB  - C5a is an important pro-inflammatory peptide involved in complement activation,
      membrane attack complex formation, immune cell chemotaxis, and allergic
      responses. Osteoarthritis is a disease characterized by degenerative changes in
      articular cartilage. It has recently been found that inflammatory responses play
      an important role in the pathogenesis of osteoarthritis and also in rheumatoid
      arthritis, where dysfunctional synoviocytes are involved. We performed a series
      of studies to verify our hypothesis that inhibition of C5a would prevent IL-1beta
      induced alternations in rat synoviocytes. In vitro studies were performed with
      RSC-364 cells to examine the role of C5a in the function of synoviocytes. RSC-364
      cells (a rat derived synovial cell line) were treated with IL-1beta, IL
      1beta+siC5a, IL-1beta+PMX205 that is antagonist of C5aR, or left untreated. Cell
      cycle, proliferation, apoptosis, invasion, as well as levels of C5a, IL-17A and
      TNF-alpha expression were evaluated. We found that IL-1beta could significantly
      increase the proliferation and invasion capabilities of RSC-364 cells, as well as
      of C5a IL-17A and TNF-alpha expression. In contrast, inhibition of C5a by siRNA
      or application of antagonist of C5aR PMX205 reversed the IL-1beta-induced changes
      in C5a expression, cell cycle, proliferation, apoptosis, invasion, and cytokines
      releases. Taken together, our study results suggest that IL-1beta can increase
      C5a expression in RSC-364 cells, and that C5a exerts a proinflammatory effect in
      RSC-364 cells. Inhibition of C5a might represent a new strategy for treating
      rheumatoid arthritis.

PMID- 30092354
TI  - Cellular phosphatase activity of C1-Ten/Tensin2 is controlled by
      Phosphatidylinositol-3,4,5-triphosphate binding through the C1-Ten/Tensin2 SH2
      domain.
AB  - Regulation of tyrosine phosphorylation on insulin receptor substrate-1 (IRS-1) is
      essential for insulin signaling. The protein tyrosine phosphatase (PTP) C1
      Ten/Tensin2 has been implicated in the regulation of IRS-1, but the molecular
      basis of this dephosphorylation is not fully understood. Here, we demonstrate
      that the cellular phosphatase activity of C1-Ten/Tensin2 on IRS-1 is mediated by
      the binding of the C1-Ten/Tensin2 Src-homology 2 (SH2) domain to
      phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3). We show that the role
      of C1-Ten/Tensin2 is dependent on insulin-induced phosphoinositide 3-kinase
      activity. The C1-Ten/Tensin2 SH2 domain showed strong preference and high
      affinity for PtdIns(3,4,5)P3. Using site-directed mutagenesis, we identified
      three basic residues in the C1-Ten/Tensin2 SH2 domain that were critical for
      PtdIns(3,4,5)P3 binding but were not involved in phosphotyrosine binding and PTP
      activity. Using a PtdIns(3,4,5)P3 binding-deficient mutant, we showed that the
      specific binding of the C1-Ten/Tensin2 SH2 domain to PtdIns(3,4,5)P3 allowed C1
      Ten/Tensin2 to function as a PTP in cells. Collectively, our findings suggest
      that the interaction between the C1-Ten/Tensin2 SH2 domain and PtdIns(3,4,5)P3
      produces a negative feedback loop of insulin signaling through IRS-1.

PMID- 30092355
TI  - The functional pathway analysis and clinical significance of miR-20a and its
      related lncRNAs in breast cancer.
AB  - BACKGROUND: miR-20a is a critical molecule in various biological processes and
      cancer progression procedures. However, its relationships with lncRNAs and their
      functional pathway analysis in breast tumorigenesis are less intensively studied.
      METHODS: The expression data from TCGA database and multiple bioinformatics
      resources were used to check the expression levels, survival curves, interactions
      and functional illustrations of miR-20a and its related lncRNAs (XIST, H19 and
      MALAT1) in breast cancer patients. The luciferase reporter assays and Pearson's
      correlation analyses were utilized to verify the direct regulatory relationship
      between miR-20a and three lncRNAs (XIST, H19 and MALAT1). In vitro cell
      proliferation, migration and invasion assays, were performed to check the
      biological effects of miR-20a and XIST in different breast cancer cell lines. The
      receiver operating characteristic curve (ROC) analyses were done for evaluating
      diagnostic values of serum miR-20a and XIST in breast cancer patients. RESULTS:
      The miR-20a expression was significantly up-regulated in both breast cancer
      samples and serum samples, and correlated with poor survival rate in breast
      cancer patients. LncRNAs (XIST, H19 and MALAT1) directly bound to hsa-miR-20a and
      were negatively correlated with hsa-miR-20a expression in breast cancer patient
      samples. For functional illustrations and downstream signaling pathways analysis,
      XIST, H19 and MALAT1 mainly shared their regulatory functions in cell motility
      and interleukin signaling in breast cancer progression. Additionally, over
      expression of miR-20a and inhibition of XIST promoted breast cancer cell growth,
      migration and invasion in vitro, and serum miR-20a and XIST served as potential
      diagnostic biomarkers for breast cancer with the area under ROC curve (AUC) of
      0.87 (95% CI = 0.78 to 0.97), and 0.78 (95% CI = 0.67 to 0.89) respectively.
      CONCLUSIONS: Taken together, these findings provide us novel insights and avenues
      for utilizing miR-20a and its related lncRNAs as potential diagnostic biomarkers
      and promising therapeutic targets for breast cancer treatment.

PMID- 30092353
TI  - Smooth muscle cell-specific FoxM1 controls hypoxia-induced pulmonary
      hypertension.
AB  - RATIONALE: Forkhead box M1 (FoxM1) is a transcription factor that promotes cell
      proliferation by regulating a broad spectrum of genes that participate in cell
      cycle regulation, such as Cyclin B, CDC25B, and Aurora B Kinase. We have shown
      that hypoxia, a well-known stimulus for pulmonary hypertension (PH), induces
      FoxM1 in pulmonary artery smooth muscle cells (PASMC) in a HIF-dependent pathway,
      resulting in PASMC proliferation, while the suppression of FoxM1 prevents hypoxia
      induced PASMC proliferation. However, the implications of FoxM1 in the
      development of PH remain less known. METHODS: We determined FoxM1 levels in the
      lung samples of idiopathic PAH (pulmonary arterial hypertension) (IPAH) patients
      and hypoxia-induced PH mice. We generated constitutive and inducible smooth
      muscle cell (SMC)-specific FoxM1 knockdown or knockout mice as well as FoxM1
      transgenic mice which overexpress FoxM1, and exposed them to hypoxia (10% O2, 90%
      N2) or normoxia (Room air, 21% oxygen) for four weeks, and measured PH indices.
      We also isolated mouse PASMC (mPASMC) and mouse embryonic fibroblasts (MEF) from
      these mice to examine the cell proliferation and expression levels of SMC
      contractile proteins. RESULTS: We showed that in hypertensive human lungs or
      mouse lungs, FoxM1 levels were elevated. Constitutive knockout of FoxM1 in mouse
      SMC caused early lethality, whereas constitutive knockdown of FoxM1 in mouse SMC
      prevented hypoxia-induced PH and PASMC proliferation. Inducible knockout of FoxM1
      in SMC reversed hypoxia-induced pulmonary artery wall remodeling in existing PH.
      Overexpression of FoxM1 enhanced hypoxia-induced pulmonary artery wall remodeling
      and right ventricular hypertrophy in mice. Alteration of FoxM1 status did not
      affect hypoxia-induced hypoxia-inducible factor (HIF) activity in mice. Knockout
      of FoxM1 decreased PASMC proliferation and induced expression of SMC contractile
      proteins and TGF-beta/Smad3 signaling. CONCLUSIONS: Our studies provide clear
      evidence that altered FoxM1 expression in PASMC contributes to PH and uncover a
      correlation between Smad3-dependent signaling in FoxM1-mediated proliferation and
      de-differentiation of PASMC.

PMID- 30092356
TI  - Influence of Wolbachia infection on mitochondrial DNA variation in the genus
      Polytremis (Lepidoptera: Hesperiidae).
AB  - The maternally inherited obligate bacteria Wolbachia is known for infecting the
      reproductive tissues of a wide range of arthropods and can contribute to
      phylogenetically discordant patterns between mtDNA and nDNA. In this study, we
      tested for an association between mito-nuclear discordance in Polytremis and
      Wolbachia infection. Six of the 17 species of Polytremis were found to be
      infected with Wolbachia. Overall, 34% (70/204) of Polytremis specimens were
      Wolbachia positive and three strains of Wolbachia identified using a wsp marker
      were further characterized as six strains based on MLST markers. Wolbachia
      acquisition in Polytremis appears to occur mainly through horizontal transmission
      rather than codivergence based on comparison of the divergence times of Wolbachia
      and Polytremis species. At the intraspecific level, one of the Wolbachia
      infections (wNas1) is associated with reduced mtDNA polymorphism in the infected
      Polytremis population. At the interspecific level, there is one case of mito
      nuclear discordance likely caused by introgression of P. fukia mtDNA into P.
      nascens driven by another Wolbachia strain (wNas3). Based on an absence of
      infected males, we suspect that one Wolbachia strain (wNas2) affects sex ratio,
      but the phenotypic effects of the other strains are unclear. These data reveal a
      dynamic interaction between Polytremis and Wolbachia endosymbionts affecting
      patterns of mtDNA variation.

PMID- 30092357
TI  - Forest corridors between the central Andes and the southern Atlantic Forest
      enabled dispersal and peripatric diversification without niche divergence in a
      passerine.
AB  - The central Andean rainforests and the Atlantic Forest are separated by the Chaco
      and the Cerrado domains. Despite this isolation, diverse evidence suggests that
      these rainforests have been connected in the past. However, little is known about
      the timing and geographic positions of these connections, as well as their
      effects on diversification of species. In this study, we used the Black-goggled
      Tanager (Trichothraupis melanops, Thraupidae) as a model to study whether the
      Andean and the Atlantic forests have acted as a refugia system, and to evaluate
      biogeographic hypotheses of diversification and connection between these
      rainforests. We compared alternative biogeographic scenarios by using Approximate
      Bayesian Computation (ABC), modeled range shifts across time, and assessed niche
      divergence between regions. The results indicated that the major phylogeographic
      gap within T. melanops is located between these rainforests. The ABC analysis
      supported peripatric diversification, with initial dispersal from the Atlantic
      Forest to the Andes during the Mid-Pleistocene. Also, the results supported an
      Andean-Atlantic forests connection through the current Cerrado-Chaco transition,
      linking the southern Atlantic Forest with the central Andes. Our findings, taken
      together with other studies, support that the connection between these biomes has
      been recurrent, and that has occurred mostly through the Cerrado and/or the
      Cerrado-Chaco transition. The data also support that the connection dynamic has
      played an important role in the biological diversification, by promoting
      peripatric divergence in some forest taxa restricted to both biomes.

PMID- 30092358
TI  - Trie-based rule processing for clinical NLP: A use-case study of n-trie, making
      the ConText algorithm more efficient and scalable.
AB  - OBJECTIVE: To develop and evaluate an efficient Trie structure for large-scale,
      rule-based clinical natural language processing (NLP), which we call n-trie.
      BACKGROUND: Despite the popularity of machine learning techniques in natural
      language processing, rule-based systems boast important advantages: distinctive
      transparency, ease of incorporating external knowledge, and less demanding
      annotation requirements. However, processing efficiency remains a major obstacle
      for adopting standard rule-base NLP solutions in big data analyses. METHODS: We
      developed n-trie to specifically address the token-based nature of context
      detection, an important facet of clinical NLP that is known to slow down NLP
      pipelines. N-trie, a new rule processing engine using a revised Trie structure,
      allows fast execution of lexicon-based NLP rules. To determine its applicability
      and evaluate its performance, we applied the n-trie engine in an implementation
      (called FastContext) of the ConText algorithm and compared its processing speed
      and accuracy with JavaConText and GeneralConText, two widely used Java ConText
      implementations, as well as with a standalone machine learning NegEx
      implementation, NegScope. RESULTS: The n-trie engine ran two orders of magnitude
      faster and was far less sensitive to rule set size than the comparison
      implementations, and it proved faster than the best machine learning negation
      detector. Additionally, the engine consistently gained accuracy improvement as
      the rule set increased (the desired outcome of adding new rules), while the other
      implementations did not. CONCLUSIONS: The n-trie engine is an efficient, scalable
      engine to support NLP rule processing and shows the potential for application in
      other NLP tasks beyond context detection.

PMID- 30092359
TI  - Choosing the best algorithm for event detection based on the intended
      application: A conceptual framework for syndromic surveillance.
AB  - There is an extensive list of methods available for the early detection of an
      epidemic signal in syndromic surveillance data. However, there is no commonly
      accepted classification system for the statistical methods used for event
      detection in syndromic surveillance. Comparing and choosing appropriate event
      detection algorithms is an increasingly challenging task. Although lists of
      selection criteria, and statistical methods used for signal detection have been
      reported, selection criteria are rarely linked to a specific set of appropriate
      statistical methods. The paper presents a practical approach for guiding
      surveillance practitioners to make an informed choice from among the most popular
      event detection algorithms based on the intended application of the algorithm. We
      developed selection criteria by mapping the assumptions and performance
      characteristics of event detection algorithms directly to important
      characteristics of the time series used in syndromic surveillance. We also
      considered types of epidemics that may be expected and other characteristics of
      the surveillance system. These guidelines will provide decisions makers, data
      analysts, public health practitioners, and researchers with a comprehensive but
      practical overview of the domain, which may reduce the technical barriers to the
      development and implementation of syndromic surveillance systems in animal and
      human health. The classification scheme was restricted to univariate and temporal
      methods because they are the most commonly used algorithms in syndromic
      surveillance.

PMID- 30092360
TI  - Molecular property diagnostic suite for diabetes mellitus (MPDSDM): An integrated
      web portal for drug discovery and drug repurposing.
AB  - Molecular Property Diagnostic Suite - Diabetes Mellitus (MPDSDM) is a Galaxy
      based, open source disease-specific web portal for diabetes. It consists of three
      modules namely (i) data library (ii) data processing and (iii) data analysis
      tools. The data library (target library and literature) module provide extensive
      and curated information about the genes involved in type 1 and type 2 diabetes
      onset and progression stage (available at http://www.mpds-diabetes.in). The
      database also contains information on drug targets, biomarkers, therapeutics and
      associated genes specific to type 1, and type 2 diabetes. A unique MPDS
      identification number has been assigned for each gene involved in diabetes
      mellitus and the corresponding card contains chromosomal data, gene information,
      protein UniProt ID, functional domains, druggability and related pathway
      information. One of the objectives of the web portal is to have an open source
      data repository that contains all information on diabetes and use this
      information for developing therapeutics to cure diabetes. We also make an attempt
      for computational drug repurposing for the validated diabetes targets. We
      performed virtual screening of 1455 FDA approved drugs on selected 20 type 1 and
      type 2 diabetes proteins using docking protocol and their biological activity was
      predicted using "PASS Online" server (http://www.way2drug.com/passonline) towards
      anti-diabetic activity, resulted in the identification of 41 drug molecules. Five
      drug molecules (which are earlier known for anti-malarial/microbial, anti-viral,
      anti-cancer, anti-pulmonary activities) were proposed to have a better
      repurposing potential for type 2 anti-diabetic activity and good binding affinity
      towards type 2 diabetes target proteins.

PMID- 30092361
TI  - The role of melatonin, a multitasking molecule, in retarding the processes of
      ageing.
AB  - Biological ageing is generally accompanied by a gradual loss of cellular
      functions and physiological integrity of organ systems, the consequential
      enhancement of vulnerability, senescence and finally death. Mechanisms which
      underlie ageing are primarily attributed to an array of diverse but related
      factors including free radical-induced damage, dysfunction of mitochondria,
      disruption of circadian rhythms, inflammaging, genomic instability, telomere
      attrition, loss of proteostasis, deregulated sensing of nutrients, epigenetic
      alterations, altered intercellular communication, and decreased capacity for
      tissue repair. Melatonin, a prime regulator of human chronobiological and
      endocrine physiology, is highly reputed as an antioxidant, immunomodulatory,
      antiproliferative, oncostatic, and endocrine-modulatory molecule. Interestingly,
      several recent reports support melatonin as an anti-ageing agent whose
      multifaceted functions may lessen the consequences of ageing. This review depicts
      four categories of melatonin's protective effects on ageing-induced molecular and
      structural alterations. We also summarize recent findings related to the function
      of melatonin during ageing in various tissues and organs.

PMID- 30092362
TI  - Cellular traffic through afferent lymphatic vessels.
AB  - The lymphatic system has long been known to serve as a highway for migrating
      leukocytes from peripheral tissue to draining lymph nodes (dLNs) and back to
      circulation, thereby contributing to the induction of adaptive immunity and
      immunesurveillance. Lymphatic vessels (LVs) present in peripheral tissues
      upstream of a first dLN are generally referred to as afferent LVs. In contrast to
      migration through blood vessels (BVs), the detailed molecular and cellular
      requirements of cellular traffic through afferent LVs have only recently started
      to be unraveled. Progress in our ability to track the migration of lymph-borne
      cell populations, in combination with cutting-edge imaging technologies, nowadays
      allows the investigation and visualization of lymphatic migration of endogenous
      leukocytes, both at the population and at the single-cell level. These studies
      have revealed that leukocyte trafficking through afferent LVs generally follows a
      step-wise migration pattern, relying on the active interplay of numerous
      molecules. In this review, we will summarize and discuss current knowledge of
      cellular traffic through afferent LVs. We will first outline how the structure of
      the afferent LV network supports leukocyte migration and highlight important
      molecules involved in the migration of dendritic cells (DCs), T cells and
      neutrophils, i.e. the most prominent cell types trafficking through afferent LVs.
      Additionally, we will describe how tumor cells hijack the lymphatic system for
      their dissemination to draining LNs. Finally, we will summarize and discuss our
      current understanding of the functional significance as well as the therapeutic
      implications of cell traffic through afferent LVs.

PMID- 30092363
TI  - Role of Ovarian Suspension in Preventing Postsurgical Ovarian Adhesions in
      Patients with Stage III-IV Pelvic Endometriosis: A Systematic Review.
AB  - Endometriosis is a benign complex gynecologic condition with high morbidity that
      affects women of reproductive age. Pelvic adhesion formation represents a serious
      clinical challenge in the management of patients with endometriosis. Several
      interventions aimed at reducing postoperative ovarian adhesion formation have
      been proposed in recent years. Here we summarize the published evidence on the
      efficacy of ovarian suspension in preventing postoperative ovarian adhesion
      formation in women undergoing laparoscopic surgery for stage III-IV
      endometriosis. The research was conducted using electronic databases. A review of
      the abstracts of all references retrieved from the search was conducted.
      Selection criteria for the systematic review included all randomized controlled
      trials (RCTs) and nonrandomized studies (NRSs) of premenopausal women diagnosed
      with stage III-IV pelvic endometriosis who underwent ovarian suspension or no
      ovarian suspension (control group). The RCTs were eligible for meta-analysis.
      Eight studies, 2 RCTs and 6 NRSs, were included in the systematic review. In all
      8 studies, ovarian suspension was performed during surgery for stage III-IV
      endometriosis. The site of the suspension was the anterior abdominal wall in
      76.8% of the cases. Five studies reported the use of polypropylene as suture for
      the suspension. Removal of the suspension suture in the postoperative period was
      reported in 6 studies. Pooled data from a meta-analysis of the RCTs show that
      women who underwent ovarian suspension had a significantly lower incidence of
      postoperative adhesion formation, particularly of moderate to severe adhesions.
      Ovarian suspension may reduce the rate and severity of postoperative adhesions
      formation in women undergoing laparoscopy for the treatment of stage III-IV
      endometriosis; however, RCTs with larger sample sizes are needed.

PMID- 30092364
TI  - Prevalence and antibiotyping of Staphylococcus aureus and methicillin-resistant
      S. aureus (MRSA) in domestic animals in India.
AB  - OBJECTIVES: Domestic animals can serve as a reservoir for antimicrobial-resistant
      Staphylococcus aureus and may lead to the emergence of drug-resistant human
      isolates. The present study aimed to assess the prevalence and antibiotypes of S.
      aureus and methicillin-resistant S. aureus (MRSA) cultured from clinical pyogenic
      cases of domestic animals in India. METHODS: A total of 100 samples were
      collected during the study (August 2014 to July 2015) from different pyogenic
      conditions of cattle (n=21), buffaloes (n=63) and dogs (n=16). Samples were
      processed for isolation and phenotypic identification of S. aureus. Species
      identification was confirmed by PCR, and all of the isolates were screened for
      the mecA gene. Antimicrobial susceptibility testing was performed by the disk
      diffusion method for 14 antimicrobial agents. RESULTS AND CONCLUSION: The study
      revealed a 40.0% prevalence of S. aureus in pyogenic clinical cases of domestic
      animals. The species-wise prevalence of S. aureus was 38.1% both in cattle and
      buffaloes and 50.0% in dogs. The study revealed 21 antibiotypes among the S.
      aureus isolates. The rate of resistance was highest for amoxicillin (95.0%),
      followed by penicillin G (82.5%). Among the 40 S. aureus isolates, 23 (57.5%)
      exhibited methicillin resistance and carried the mecA gene. To the best of our
      knowledge based on the available literature, this is the first report of its kind
      from this country.

PMID- 30092365
TI  - Pragmatic combinations of acupuncture points for lateral epicondylalgia are
      unreliable in the physiotherapy setting.
AB  - This study describes the reliability of pragmatic combinations of acupuncture
      points for lateral epicondylalgia as prescribed by physiotherapists who were
      experts in acupuncture. Raters (n=14; 33 to 59 years) independently prescribed
      acupuncture points for 30 simulated human patients with lateral epicondylalgia
      who were surveyed via a printed questionnaire. The frequency and cooccurrence of
      acupuncture points prescribed for patients with lateral epicondylitis were
      assessed. Absolute agreement and Light's kappa (kappaLight) with 95%CI were used
      to quantify the interrater agreement. Raters prescribed 103 unique acupuncture
      points in different combinations with a median [min; max] of 5 [0; 11]
      acupuncture points. The most prescribed acupuncture point was LI-11
      (297/420=71%), and the most common cooccurring acupuncture points were LI-11 and
      LI-4 (160/420=38%). The absolute agreement for prescribing the acupuncture points
      ranged from 70% (point GB-20) to 0% (points LI-10, SP-6, LI-11, GB-34, LI-12, and
      LI-4). Point LR-3 showed the highest interrater reliability for prescribing the
      acupuncture points (kappaLight=0.112, 95%CI=[0.055; 0.194]), whereas point LI-4
      showed the lowest reliability (kappaLight=-0.003, 95%CI=[-0.024; 0.024]). These
      findings suggest that pragmatic prescriptions of acupuncture points for lateral
      epicondylalgia are unreliable among physiotherapists who are experts in
      acupuncture. Explicit, high-level evidence-based rules for prescribing and
      teaching combinations of acupuncture points for lateral epicondylalgia are
      warranted.

PMID- 30092366
TI  - 8-Aryl-6-chloro-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridines as potent
      antitrypanosomatid molecules bioactivated by type 1 nitroreductases.
AB  - Based on a previously identified antileishmanial 6,8-dibromo-3-nitroimidazo[1,2
      a]pyridine derivative, a Suzuki-Miyaura coupling reaction at position 8 of the
      scaffold was studied and optimized from a 8-bromo-6-chloro-3-nitroimidazo[1,2
      a]pyridine substrate. Twenty-one original derivatives were prepared, screened in
      vitro for activity against L. infantum axenic amastigotes and T. brucei brucei
      trypomastigotes and evaluated for their cytotoxicity on the HepG2 human cell
      line. Thus, 7 antileishmanial hit compounds were identified, displaying IC50
      values in the 1.1-3 MUM range. Compounds 13 and 23, the 2 most selective
      molecules (SI = >18 or >17) were additionally tested on both the promastigote and
      intramacrophage amastigote stages of L. donovani. The two molecules presented a
      good activity (IC50 = 1.2-1.3 MUM) on the promastigote stage but only molecule
      23, bearing a 4-pyridinyl substituent at position 8, was active on the
      intracellular amastigote stage, with a good IC50 value (2.3 MUM), slightly lower
      than the one of miltefosine (IC50 = 4.3 MUM). The antiparasitic screening also
      revealed 8 antitrypanosomal hit compounds, including 14 and 20, 2 very active
      (IC50 = 0.04-0.16 MUM) and selective (SI = >313 to 550) molecules toward T.
      brucei brucei, in comparison with drug-candidate fexinidazole (IC50 = 0.6 & SI >
      333) or reference drugs suramin and eflornithine (respective IC50 = 0.03 and 13.3
      MUM). Introducing an aryl moiety at position 8 of the scaffold quite
      significantly increased the antitrypanosomal activity of the pharmacophore.
      Antikinetoplastid molecules 13, 14, 20 and 23 were assessed for bioactivation by
      parasitic nitroreductases (either in L. donovani or in T. brucei brucei), using
      genetically modified parasite strains that over-express NTRs: all these molecules
      are substrates of type 1 nitroreductases (NTR1), such as those that are
      responsible for the bioactivation of fexinidazole. Reduction potentials measured
      for these 4 hit compounds were higher than that of fexinidazole (-0.83 V),
      ranging from -0.70 to -0.64 V.

PMID- 30092367
TI  - Novel spiroindoline HDAC inhibitors: Synthesis, molecular modelling and
      biological studies.
AB  - This paper describes the rational development of a series of novel spiroindoline
      derivatives endowed with selective inhibitory activity on the HDAC6 isoform. A
      convenient multicomponent one-pot protocol was applied for the assembly of the
      desired N1-substituted spiroindoline core which allowed a straightforward
      analoging. Computational studies and in vitro determination of inhibitory potency
      for the developed compounds against HDAC6 and HDAC1 isoforms were flanked by cell
      based studies on histone H3 and alpha-tubulin acetylation. The effects on cancer
      cell cycle and apoptosis of the best performing derivatives were assessed on
      cancer cell lines highlighting a promising antitumor potential. In view of cell
      based data and calculated drug-like properties, the selective HDAC6 inhibitor 5b,
      with a spiroindoline-based hydroxamate bearing a tert-butyl carbamate
      functionality, was selected to be further investigated for its potential in
      inhibiting tumor cells migration. It was able to potently inhibit cell migration
      in SH-SY5Y neuroblastoma cells and did not display toxicity in NIH3T3 mouse
      fibroblasts. Taken together, these data foster further investigation and
      optimization for this class of compounds as novel anticancer agents.

PMID- 30092369
TI  - Variants in immune-related genes and genital HPV 16 persistence in men.
AB  - OBJECTIVES: While most human papillomavirus (HPV) infection clears on its own,
      persistent HPV infection can cause genital warts and anal, penile and
      oropharyngeal cancers in men. We conducted genetic analysis in a sub-cohort of
      the HPV infection in men (HIM) study to test the hypothesis that differences in
      host genes influence HPV persistence in men. METHODS: Baseline and longitudinal
      genital HPV status at the genitals was measured every 6-months using the Linear
      Array assay amplified HPV L1 gene fragment using the PGMY09/11 L1 consensus
      primer system. DNA was extracted from peripheral blood and single nucleotide
      polymorphisms (SNPs) in the customized genome-wide genotyping array, the
      "TxArray," were examined using logistic regression in a case-control study design
      to assess the association with HPV16 persistence/clearance. RESULTS: Of the total
      of 737,742 autosomal SNPs in the array, 605,885 passed basic quality control and
      were examined between 40 men (cases) with > 18 months persistent genital HPV 16
      infection vs. 151 controls who were HPV 16-positive, but whose infections cleared
      in < 18 months. The logistic regression analysis from this case-control study
      showed variants in several gene regions associated with genital HPV 16
      persistence, with the strongest association detected with SNPs on chromosomes 20
      (p < 5.72 * 10-6) and 15 (p < 5.89 * 10-6), after adjusting for age, smoking
      status, number of sex partners and four principal components (ancestral
      background). CONCLUSIONS: Our results provide a preliminary basis for
      understanding the biological mechanism of oncogenic HPV 16 pathogenesis at the
      genitals in men. Some of the genes flanking the top hit SNPs are consistent with
      previous findings in both HPV related and non-related cancers but further genetic
      studies in larger cohorts are warranted to confirm these and identify novel major
      susceptibility genes involved in the pathogenesis of genital HPV persistence in
      men.

PMID- 30092368
TI  - Design, synthesis and pharmacological evaluation of new 3-(1H-benzimidazol-2
      yl)quinolin-2(1H)-one derivatives as potential antitumor agents.
AB  - A series of new 3-(1H-benzimidazol-2-yl)quinolin-2(1H)-one derivatives (5a1-5d6)
      were designed and synthesized as antitumor agents. In vitro antitumor assay
      results showed that some compounds exhibited moderate to high inhibitory activity
      against HepG2, SK-OV-3, NCI-H460 and BEL-7404 tumor cell lines, and most
      compounds exhibited much lower cytotoxicity against the HL-7702 normal cell line
      compared to 5-FU and cisplatin. In vivo antitumor assay results demonstrated that
      5a3 exhibited effective inhibition on tumor growth in the NCI-H460 xenograft
      mouse model and that 5d3 displayed excellent antiproliferative activity in the
      BEL-7402 xenograft model. These results suggested that both 5a3 and 5d3 could be
      used as anticancer drug candidates. Mechanistic studies suggested that compounds
      5a3 and 5d3 exerted their antitumor activity by up-regulation of Bax,
      intracellular Ca2+ release, ROS generation, downregulation of Bcl-2, activation
      of caspase-9 and caspase-3 and subsequent cleavage of PARP, inhibition of CDK
      activity and activation of the p53 protein.

PMID- 30092370
TI  - Active agents, biomaterials, and technologies to improve biolubrication and
      strengthen soft tissues.
AB  - Normal functioning of articulating tissues is required for many physiological
      processes occurring across length scales from the molecular to whole organism.
      Lubricating biopolymers are present natively on tissue surfaces at various sites
      of biological articulation, including eyelid, mouth, and synovial joints. The
      range of operating conditions at these disparate interfaces yields a variety of
      tribological mechanisms through which compressive and shear forces are dissipated
      to protect tissues from material wear and fatigue. This review focuses on recent
      advances in active agents and biomaterials for therapeutic augmentation of
      friction, lubrication, and wear in disease and injured states. Various small
      molecule, biological, and gene delivery therapies are described, as are
      tribosupplementation with naturally-occurring and synthetic biolubricants and
      polymer reinforcements. While reintroduction of a diseased tissue's native
      lubricant received significant attention in the past, recent discoveries and pre
      clinical research are capitalizing on concurrent advances in the molecular
      sciences and bioengineering fields, with an understanding of the underlying
      tissue structure and physiology, to afford a desired, and potentially patient
      specific, tissue mechanical response for restoration of normal function. Small
      and large molecule drugs targeting recently elucidated pathways as well as
      synthetic and hybrid natural/synthetic biomaterials for restoring a desired
      tissue mechanical response are being investigated for treatment of, for example,
      keratoconjunctivitis sicca, xeroderma, and osteoarthritis.

PMID- 30092371
TI  - In situ-forming, cell-instructive hydrogels based on glycosaminoglycans with
      varied sulfation patterns.
AB  - Glycosaminoglycan (GAG)-based hydrogels were proven highly effective to direct
      cell fate decisions by modulating the administration of cytokines. The sulfation
      pattern of the GAG component critically controls its affinity to proteins and
      thus governs the release of cytokines from GAG-containing gel systems. To apply
      this principle in the design of in situ assembling materials suitable for cell
      embedding and injection into tissues, we developed a platform of bio-orthogonally
      crosslinked star-shaped poly(ethylene glycol) (starPEG)-GAG hydrogels that
      display variable GAG sulfation patterns. Combining rational design for tuning the
      hydrogel network properties and a reaction-diffusion model for predicting
      transport processes within the matrices, we exemplarily applied the resulting
      materials for tailoring morphogenic and chemotactic gradients of platelet-derived
      growth factor-BB (PDGF-BB) in 3D. Conditions identified with this approach were
      demonstrated to effectively control the fate and morphogenesis of embedded
      mesenchymal stem cells (MSCs). Adjusting the sulfation patterns of
      glycosamnioglycans used in the preparation of in situ forming hydrogels is thus
      concluded to create new powerful options for modulating biomolecular signals in
      cell fate control, paving the way for advanced 3D cultures and precision tissue
      engineering.

PMID- 30092373
TI  - Developmental competence of buffalo (Bubalus bubalis) denuded oocytes cocultured
      with cumulus cells: Protective role of cumulus cells.
AB  - The objectives of the present study were to evaluate the developmental competence
      of buffalo denuded oocytes (DOs) cocultured with cumulus cells (CCs) during in
      vitro maturation, and to investigate the mechanisms by which CCs promote oocyte
      maturation and development. Buffalo oocytes were matured in vitro for 24 h in
      three groups: (1) intact cumulus-oocyte complexes (COCs) (2) DOs cocultured with
      CCs (DOsCC), and (3) DOs cultured alone (DOs). Matured oocytes were used to
      determine the relative mRNA abundance of Gdf-9, Bmp15, Zar1, Caspase-3, Bcl-2,
      Zp2, Zp3, Cd9 and Pde3a by Rt-qPCR and CASPASE-3 protein expression by
      immunofluorescence. The intracellular content of cGMP, cAMP and MPF activity and
      the rate of embryonic development were also assessed. Results of the present
      study showed that in DOs, the relative mRNA abundance of Gdf-9, Bmp15, and Cd9
      significantly (P < 0.05) decreased, whereas Caspase-3 (mRNA and protein levels),
      Bcl-2, and Pde3a exhibited higher expression than DOsCC and COCs. However, there
      was no significant difference among the groups in the expression level of Zar-1,
      Zp2, and Zp3. The intracellular content of cAMP and MPF activity was notably
      higher (P < 0.05) in DOs compared to COCs and DOsCC. There was no significant
      difference between COCs and DOsCC in cGMP content, which was significantly lower
      (P < 0.05) in DOs. Moreover, the cleavage and blastocyst rates were 58.4 +/-
      1.8%, 43.7 +/- 1.1%, 18.4 +/- 0.9% and 18.0 +/- 1.3%, 11.0 +/- 0.9% and 4.5 +/-
      0.6% in COCs, DOsCC and DOs groups, respectively. In conclusion, the presence of
      CCs protects buffalo DOs from apoptosis and promotes maturation through
      regulation of the intracellular content of cAMP and MPF activity and improves the
      fertilizing capacity of oocytes through modulation of the gamete fusion gene,
      Cd9.

PMID- 30092372
TI  - Functional characterization of NANOG in goat pre-implantation embryonic
      development.
AB  - Nanog as a novel pluripotent cell-specific gene plays important roles in
      regulation of signaling pathways for maintenance and induction of pluripotency in
      inner cell mass (ICM) and embryonic stem cells (ESC) in mouse. The molecular
      features and transcription regulation of NANOG gene in domestic animals are not
      well defined. In this study, we performed knockdown of NANOG mRNA in goat embryos
      and examined its effect on early embryonic development. Presumptive zygotes were
      injected with a volume of 8-10 pl NANOG or scrambled (SCR) siRNA, and
      subsequently cleavage and blastocyst formation rate were assessed. Furthermore,
      gene expression analysis was carried out in 6-8 cell and blastocyst derived
      embryos from non-injected controls, SCR - and siRNA-injected presumptive zygotes.
      Cleavage and blastocyst rates in siRNA groups were insignificantly lower than the
      control and SCR groups. Embryos with reduced expression of NANOG showed decrease
      in number of trophectoderm (TE) and total cells in blastocysts. Analysis of
      expression of developmentally important genes (SOX2, OCT4 and NANOG), which work
      as a network, showed that NANOG knockdown results in significant increase in
      expression of SOX2 and OCT4 and among the possible target genes (CDX2, REX1 and
      GATA4) of this network, only GATA4 showed increased expression. Our results
      suggest that NANOG is likely to be required for proliferation of trophoblastic
      cells.

PMID- 30092374
TI  - Lysophosphatidic acid enhances PGE2 to PGF2alpha ratio and nitric oxide level in
      nonpregnant buffalo uterus.
AB  - Lysophosphatidic acid (LPA) is a small ubiquitous lipid exerting diverse
      biological functions. Its role in reproduction in different species has created
      great interest in recent times. In the present study, we aimed to elucidate LPA
      signaling in nonpregnant buffalo uterus by in vitro studies. Standard techniques
      like real-time PCR (for mRNA expression of LPARs and COX-2 and iNOS), Western
      blot (for PPARgamma protein expression), sandwich ELISA (for PGE2 and PGF2alpha
      assay) and histopathology (for assessment of endometrial architecture in culture)
      were used in this study. The buffalo uterine tissues were collected from the
      local slaughterhouse and were selected for the study on the basis of the presence
      of corpus luteum on the ovary (n = 5). The LPAR3 receptor was the highest
      expressed receptor as compared to LPAR1 and LPAR6 in non-pregnant uterine tissues
      after 6 h incubation in Dulbecco's Modified Eagle Medium (DMEM). 50 MUM LPA
      increased the mRNA expressions of COX-2 and iNOS enzymes which were attenuated by
      the treatment of LPAR1/3 antagonist Ki16425. PPARgamma antagonist GW9662
      prevented the LPA-induced increase in iNOS mRNA expression but did not alter the
      COX-2 expression. LPA also enhanced the PGE2 to PGF2alpha ratio in uterine tissue
      homogenates which was inhibited by all the receptor antagonists as well as by the
      inhibitors of COX-2 and iNOS. LPA also increased the total nitrite level in
      tissue homogenates in LPAR1/3- and iNOS-dependent manner. Additionally, we
      demonstrate PPARgamma mRNA and protein expressions in nonpregnant buffalo
      endometrium. In conclusion, the results of the present study suggest that LPA
      acts as a luteotropic factor during the estrus cycle in nonpregnant buffalo
      uterus by enhancing PGE2 to PGF2alpha ratio and NO level through multiple
      receptors.

PMID- 30092375
TI  - Different protocols using PGF2alpha as ovulation inducer in Nelore cows subjected
      to estradiol-progesterone timed AI based protocols.
AB  - The objective of this study was to evaluate the effect of a PGF2alpha-analogue
      (PGF) on ovulation and pregnancy rates after timed artificial insemination (TAI)
      in cattle. In Experiment 1 cows received an intravaginal progesterone-releasing
      device (CIDR) plus 2 mg im of estradiol benzoate (EB) on Day 0. The CIDR devices
      were removed on Day 8, and all cows received 150 MUg im of d-cloprostenol
      (PGF2alpha-analogue), 300 IU of eCG and 1 mg of estradiol cypionate (ECP) im. On
      Day 9, cows were randomly assigned into two groups: 1) ECP Group (n = 17), that
      did not receive any further treatment; and 2) ECP-PG Group (n = 14) that were
      given 150 MUg of d-cloprostenol (PGF) as adjuvant stimulus for ovulation. No
      difference between groups was detected in interval for ovulation (P = 0.5), and
      in the proportion of cows ovulating (P = 0.09). In Experiment 2, multiparous
      suckling crossbred Aberdeen Angus cows (n = 260), were treated into two groups,
      similarly as Experiment 1; ECP group (n = 122), and ECP-PG group (n = 138). All
      females were TAI on Day 10. The proportion of cows treated with ECP that became
      pregnant was 54.9% (67/122), and cows treated with ECP plus PGF was 55.1%
      (76/138; P = 0.9). In Experiment 3, 686 Nelore cows, 40 to 50 days postpartum,
      were treated as Experiment 1 (ECP group), however, on Day 8 cows were divided
      into 3 groups: ECP Group (n = 216); PGF-SC Group (n = 228), in which cows did not
      receive ECP and were given an additional subcutaneous injection of PGF on Day 8;
      and PGF-IM Group (n = 242), in which cows also did not receive ECP on Day 8 and
      were given an additional injection of PGF im on Day 9. On Day 10, estrus was
      evaluated at timed AI (TAI). There was no difference in the diameter of the
      dominant follicle at CIDR removal and at TAI, and pregnancy per AI among groups
      (P > 0.05). However, the proportion of cows that displayed estrus between CIDR
      removal and TAI was higher in ECP group than in PGF-SC and PGF-IM groups (P <
      0.001). Cows that displayed estrus has higher P/AI than cows that did not (P =
      0.008). In conclusion, these results suggested that intramuscular or subcutaneous
      injection of PGF2alpha could be successfully used to induce ovulation in cattle
      undergoing TAI, with similar pregnancy rates when compared with ECP. The
      subcutaneous injection of PGF on the same day of CIDR removal could be an
      interesting alternative due it reduces cattle management to obtain similar
      results.

PMID- 30092376
TI  - Fine tuning neuronal targeting of nanoparticles by adjusting the ligand grafting
      density and combining PEG spacers of different length.
AB  - : Poly(ethylene glycol) (PEG) has been extensively used to coat the surface of
      nanocarriers to improve their physicochemical properties and allow the grafting
      of targeting moieties. Still, to date there is no common agreement on the ideal
      PEG coverage-density or length to be used for optimum vector performance. In this
      study, we aimed to investigate the impact of both PEG density and length on the
      vectoring capacity of neuron-targeted gene-carrying trimethyl chitosan
      nanoparticles. The non-toxic fragment from the tetanus toxin (HC) was coupled to
      a 5 kDa heterobifunctional PEG (HC-PEG5k) reactive for the thiol groups inserted
      into the polymer backbone and grafted at different densities onto the
      nanoparticles. Internalization and transfection studies on neuronal versus non
      neuronal cell lines allowed to determine the PEG density of 2 mol% of PEG chains
      per mol of primary amine groups as the one with superior biological performance.
      To enhance HC exposure and maximize cell-nanoparticle specific interaction, NPs
      containing different ratios of HC-PEG5k and 2 kDa methoxy-PEG at the same
      grafting density were produced. By intercalating HC-PEG5k with methoxy-PEG2k we
      attained the best performance in terms of internalization (higher payload
      delivery into cells) and transfection efficiency, using twice lower amount of HC.
      This outcome highlights the need for fine-tuning of PEG-modified nanoparticles
      towards the achievement of optimal targeting. STATEMENT OF SIGNIFICANCE: The
      amount and exposure of targeting moieties at a nanoparticle surface are critical
      parameters regarding the targeting potential of nanosized delivery vectors.
      However, to date, few studies have considered fundamental aspects impacting the
      ligand-receptor pair interaction, such as the effect of spacer chain length,
      flexibility or conformation. By optimizing the PEG spacer density and chain
      length grafted into nanoparticles, we were able to establish the formulation that
      maximizes cell-nanoparticle specific interaction and has superior biological
      performance. Our work shows that the precise adjustment of the PEG coverage
      density presents a significant impact on the selectivity and bioactivity of the
      developed formulation, emphasizing the need for the fine-tuning of PEG-modified
      nanoparticles for the successful development of the next-generation
      nanomedicines.

PMID- 30092377
TI  - Direct cell-cell communication with three-dimensional cell morphology on wrinkled
      microposts.
AB  - : Cell-cell communication plays a critical role in a myriad of processes, such as
      homeostasis, angiogenesis, and carcinogenesis, in multi-cellular organisms.
      Monolayer cell models have notably improved our understanding of cellular
      interactions. However, the cultured cells on the planar surfaces adopt a two
      dimensional morphology, which poorly imitates cellular organization in vivo,
      providing physiologically-irrelevant cell responses. Non-planar surfaces
      comprising various patterns have demonstrated great abilities in directing
      cellular growth and producing different cell morphologies. In recent years, a few
      topographical substrates have provided valuable information about cell-cell
      signalling, however, none of these studies have reported a three-dimensional (3D)
      cell morphology. Here, we introduce a structurally tunable topographical platform
      that can maintain cell coupling while inducing a true 3D cell morphology. Optical
      imaging and fluorescence recovery after photobleaching are used to illustrate
      these capabilities. Our analyses suggest that the intercellular signalling on the
      present platform, which we propose is mainly through gap junctions, is comparable
      to that in natural tissue. STATEMENT OF SIGNIFICANCE: A better understanding of
      direct cellular communication can help treating neurological diseases and
      cancers, which may be caused by dysfunctional intercellular signaling. To
      investigate cell-cell contact, cells are conventionally plated onto planar
      surfaces, where they flatten and adopt a two-dimensional cell morphology. These
      unrealistic models are physiologically-irrelevant since cells exhibit a three
      dimensional (3D) shape in the body. Therefore, porous scaffolds and topographical
      surfaces, capable of inducing various cell morphologies, have been introduced, in
      which the latter is more desirable for sample imaging and screening. However, the
      few non-planar substrates used to study cell coupling have not produced a 3D cell
      shape. Here, we present a tunable culture platform that can control direct cell
      cell communication while maintaining true 3D cell morphologies.

PMID- 30092378
TI  - Lessons to be learned and future directions for intervertebral disc biomaterials.
AB  - : Biomaterials science has achieved significant advancements for the replacement,
      repair and regeneration of intervertebral disc tissues. However, the translation
      of this research to the clinic presents hurdles. The goal of this paper is to
      identify strategies to recapitulate the intrinsic complexities of the
      intervertebral disc, to highlight the unresolved issues in basic knowledge
      hindering the clinical translation, and finally to report on the emerging
      technologies in the biomaterials field. On this basis, we identify promising
      research directions, with the hope of stimulating further debate and advances for
      resolving clinical problems such as cervical and low back pain using biomaterial
      based approaches. STATEMENT OF SIGNIFICANCE: Although not life-threatening,
      intervertebral disc disorders have enormous impact on life quality and
      disability. Disc function within the human body is mainly mechanical, and
      therefore the use of biomaterials to rescue disc function and alleviate pain is
      logical. Despite intensive research, the clinical translation of biomaterial
      based therapies is hampered by the intrinsic complexity of this organ. After
      decades of development, artificial discs or tissue replacements are still niche
      applications given their issues of integration and displacement with detrimental
      consequences. The struggles of biological therapies and tissue engineering are
      therefore understandable. However, recent advances in biomaterial science give
      new hope. In this paper we identify the most promising new directions for
      intervertebral disc biomaterials.

PMID- 30092379
TI  - Catabolism of phenylacetic acid in Penicillium rubens. Proteome-wide analysis in
      response to the benzylpenicillin side chain precursor.
AB  - : Biosynthesis of benzylpenicillin in filamentous fungi (e.g. Penicillium
      chrysogenum - renamed as Penicillium rubens- and Aspergillus nidulans) depends on
      the addition of CoA-activated forms of phenylacetic acid to isopenicillin N.
      Phenylacetic acid is also detoxified by means of the homogentisate pathway, which
      begins with the hydroxylation of phenylacetic acid to 2-hydroxyphenylacetate in a
      reaction catalysed by the pahA-encoded phenylacetate hydroxylase. This catabolic
      step has been tested in three different penicillin-producing strains of P. rubens
      (P. notatum, P. chrysogenum NRRL 1951 and P. chrysogenum Wisconsin 54-1255) in
      the presence of sucrose and lactose as non-repressing carbon sources. P.
      chrysogenum Wisconsin 54-1255 was able to accumulate 2-hydroxyphenylacetate at
      late culture times. Analysis of the P. rubens genome showed the presence of
      several PahA homologs, but only Pc16g01770 was transcribed under penicillin
      production conditions. Gene knock-down experiments indicated that the protein
      encoded by Pc16g01770 seems to have residual activity in phenylacetic acid
      degradation, this catabolic activity having no effect on benzylpenicillin
      biosynthesis. Proteome-wide analysis of the Wisconsin 54-1255 strain in response
      to phenylacetic acid revealed that this molecule has a positive effect on some
      proteins directly related to the benzylpenicillin biosynthetic pathway, the
      synthesis of amino acid precursors and other important metabolic processes.
      SIGNIFICANCE: The adaptive response of Penicillium rubens to benzylpenicillin
      production conditions remains to be fully elucidated. This article provides
      important information about the molecular mechanisms interconnected with
      phenylacetate (benzylpenicillin side chain precursor) utilization and penicillin
      biosynthesis, and will contribute to the understanding of the complex physiology
      and adaptation mechanisms triggered by P. rubens (P. chrysogenum Wisconsin 54
      1255) under benzylpenicillin production conditions.

PMID- 30092380
TI  - Transcriptome-facilitated proteomic characterization of rear-fanged snake venoms
      reveal abundant metalloproteinases with enhanced activity.
AB  - High-throughput technologies were used to identify venom gland toxin expression
      and to characterize the venom proteomes of two rear-fanged snakes, Ahaetulla
      prasina (Asian Green Vine Snake) and Borikenophis portoricensis (Puerto Rican
      Racer). Sixty-nine complete toxin-coding transcripts from 12 venom protein
      superfamilies (A. prasina) and 50 complete coding transcripts from 11 venom
      protein superfamilies (B. portoricensis) were identified in the venom glands.
      However, only 18% (A. prasina) and 32% (B. portoricensis) of the translated
      protein isoforms were detected in the proteome of these venoms. Both venom gland
      transcriptomes and venom proteomes were dominated by P-III metalloproteinases.
      Three-finger toxins, cysteine-rich secretory proteins, and C-type lectins were
      present in moderate amounts, but other protein superfamilies showed very low
      abundances. Venoms contained metalloproteinase activity comparable to viperid
      snake venom levels, but other common venom enzymes were absent or present at
      negligible levels. Western blot analysis showed metalloproteinase and cysteine
      rich secretory protein epitopes shared with the highly venomous Boomslang
      (Dispholidus typus). The abundance of metalloproteinases emphasizes the important
      trophic role of these toxins. Comprehensive, transcriptome-informed definition of
      proteomes and functional characterization of venom proteins in rear-fanged snake
      families help to elucidate toxin evolution and provide models for protein
      structure-function analyses.

PMID- 30092381
TI  - Quantitative proteomics of psychotrophic diazotroph in response to nitrogen
      deficiency and cold stress.
AB  - : Effective protocols and novel biomarkers are the need of this hour to screen
      potential cold adapted diazotrophs for sustainable mountain agricultural plans.
      LC-MS/MS based gel less quantitative proteomics was employed to investigate the
      metabolic response of Himalayan cold adapted diazotroph Pseudomonas palleroniana
      N26 (JN055435) for nitrogen deficiency and cold stress. More than 5000 proteins
      were identified, and 125 of them showed significant difference with a 2-fold or
      greater change (p < .05) between normal and stress conditions, including 29 up
      regulated proteins and 35 down-regulated proteins. Expression of nifA, nifL,
      nifH, nifB, nifD, and nifK during N2 fixing conditions reveals that nitrogenase
      system was successfully activated. Further, 8% of the upregulated proteins showed
      similarity with uncharacterized proteins of several nitrogen fixing genera which
      suggests their in-depth investigation. Additionally, as per earlier studies, cowN
      was differentially expressed under nitrogen fixing conditions; thereby,
      confirming its potential to be a potent biomarker for monitoring the nitrogen
      fixation in cold niches. BIOLOGICAL SIGNIFICANCE: Understanding of nitrogenase
      expression and regulation is essential to employ potential diazotrophs under
      diverse ecological niches to achieve agricultural as well as environmental
      sustainability. The molecular mechanisms of cold adapted diazotrophy are still
      unaddressed. In this scenario, present study, besides characterizing diazotrophic
      proteins, is helpful in identifying the protein(s) or a biomarker viz. CowN to
      facilitate the monitoring of nitrogen fixation in cold niches. To the best of our
      knowledge, this is the first gel-less quantitative free-living diazotrophic
      proteome study using label free mass spectrometry having high mass accuracy in
      both MS and MS/MS scans. It enriches the diazotrophic proteome database and will
      complement the other "omics" technologies for improved crop protection and
      sustainability strategies.

PMID- 30092382
TI  - Measuring the involvement in family life of children with autism spectrum
      disorder: A DBPNet study.
AB  - BACKGROUND: Children with Autism Spectrum Disorder (ASD) have social and
      communication deficits that impair their involvement in family life. No measures
      of child involvement in the family have been validated for the ASD population.
      AIM: To evaluate the validity of a measure of Family Involvement (FI) of children
      ages 5-12 with ASD. METHOD: Parents of children ages 5-12 with ASD (n = 114)
      completed FI items from the PROMIS(r) pediatric Family Relationships item bank in
      computerized adaptive testing (CAT) format, as well as measures of ASD symptom
      burden, parenting stress, and parental depression. Medical record review provided
      child intelligence or developmental quotient. A reference sample (n = 236)
      closely matching the ASD sample in age and gender was created from the national
      standardization sample, and underwent a simulated CAT. RESULTS: The CAT precisely
      and efficiently measured parent-reported FI of children with ASD. Average FI
      scores were lower among children with ASD (M = 46.3, SD = 7.1) than children in
      the reference sample (M = 52.5, SD = 9.1). A "dose response" decrease in FI was
      observed as ASD severity increased. Increased parenting stress was associated
      with lower FI. No relationship between FI and child IQ was found. CONCLUSION: The
      FI items captured FI among children ages 5-12 with ASD with acceptable precision.
      Reduced FI among children with ASD, particularly those with higher symptom
      severity, suggests validity of the items in this population.

PMID- 30092383
TI  - The exploitation of fresh remains by Dermestes maculatus De Geer (Coleoptera,
      Dermestidae) and their ability to cause a localised and prolonged increase in
      temperature above ambient.
AB  - This article discusses the ability of adults of the coleopteran beetle Dermestes
      maculatus (De Geer) to colonise fresh remains. It also considers whether
      colonisation results in localised thermogenesis in a similar manner to that
      induced by blowfly larvae. In the laboratory, adult D. maculatus instantly
      colonised fresh killed rats and mice. The adults entered the oral cavity within 1
      2 h and the eyes and ears were among the first parts of the body consumed. Egg
      laying occurred on the torso and head within an hour of death and eggs hatched
      within 3-4 days. The larvae remained on the body whilst the adults (>70%) rested
      in the surrounding wood chippings when not feeding or laying eggs. Larvae grew
      rapidly on the dead bodies and some were starting to pupate within 28 days. The
      dermestids consumed the corpses predominantly from the head downwards and weight
      loss correlated with the number of larvae produced. In both rats and mice,
      colonisation of the abdominal region was associated with an increase in
      temperature. The maximum abdominal temperature and the length of time the
      temperature remained 1  degrees C or more above ambient correlated with the
      number of larvae produced. This rise in temperature would probably be sufficient
      to increase the rate of development of dermestid larvae and that of any other
      invertebrate or microbe in the region. In the absence of dermestids, the internal
      temperature rarely rose 1  degrees C above ambient. Although there are previously
      published accounts of dermestid beetles consuming fresh corpses, they are reputed
      to favour older desiccated remains. This paper confirms that D. maculatus rapidly
      consumes and reproduces on fresh remains. The fact that dermestid beetles are
      seldom found on fresh remains under field conditions is therefore probably a
      result of inter-specific competition among decomposing insects rather than food
      preference. This information could be useful when determining the forensic
      significance of D. maculatus recovered from dead bodies.

PMID- 30092384
TI  - Bioactive compounds from sclerotia extract of Poria cocos that control adipocyte
      and osteoblast differentiation.
AB  - Poria cocos Wolf confers edible sclerotia also known as 'Indian bread' in North
      America, that have been used for the treatment of various diseases in Asian
      countries. As part of our ongoing aim to identify biologically new metabolites
      from Korean edible mushrooms, we investigated the ethanol (EtOH) extract of the
      sclerotia of P. cocos by applying a comparative LC/MS- and bioassay-based
      analysis approach, since the EtOH extract reciprocally regulated adipocyte and
      osteoblast differentiation in mouse mesenchymal stem cells (MSCs). Bioassay-based
      analysis of the EtOH extract led to the successful isolation of two sterols,
      ergosterol peroxide (1) and 9,11-dehydroergosterol peroxide (2); three
      diterpenes, dehydroabietic acid (3), 7-oxocallitrisic acid, (4) and pimaric acid
      (5); and two triterpenes, dehydroeburicoic acid monoacetate (6) and eburicoic
      acid acetate (7) from the active hexane-soluble fraction. The isolated compounds
      (1-7) were examined for their effects on the regulation of MSC differentiation.
      The two sterols (1 and 2) were able to suppress MSC differentiation toward
      adipocytes. In contrast, the three diterpenes (3-5) showed activity to promote
      osteogenic differentiation of MSC. These findings demonstrate that the EtOH
      extract of P. cocos sclerotia is worth consideration as a new potential source of
      bioactive compounds effective in the treatment of osteoporosis in the elderly,
      since the extract contains sterols that inhibit adipogenic differentiation as
      well as diterpenes that promote osteogenic differentiation from MSCs.

PMID- 30092385
TI  - Six kanshone C-derived sesquiterpenoid hybrids nardochalaristolones A-D,
      nardoflavaristolone A and dinardokanshone F from Nardostachys jatamansi DC.
AB  - Four sesquiterpenoid-chalcone hybrids (nardochalaristolones A-D, 1-4), a pair of
      epimeric sesquiterpenoid-flavonone hybrids ((2'S)- and (2'R)-nardoflavaristolone
      A, 5 and 6), and a sesquiterpenoid dimer (dinardokanshone F, 7), all sharing a
      kanshone C-derived sesquiterpenoid unit, were isolated from the underground parts
      of Nardostachys jatamansi (D.Don) DC. Their structures were elucidated by
      analysis of the extensive spectroscopic data, and the absolute configurations
      were established by analysis of 2D NMR spectroscopic data including NOESY data,
      combined with comparisons of experimental and calculated electronic circular
      dichroism spectra. Further, the plausible biosynthetic pathways for these
      compounds were proposed. And the results of SERT activity assay revealed that
      nardochalaristolones C-D (3 and 4) and nardoflavaristolone A (5 and 6)
      significantly enhanced SERT activity, while other compounds didn't show any SERT
      regulatory activities.

PMID- 30092386
TI  - How scientific literature analysis yields innovative therapeutic hypothesis
      through integrative iterations.
AB  - It is becoming generally accepted that the current diagnostic system often
      guarantees, rather than diminishes, disease heterogeneity. In effects, syndrome
      dominated conceptual thinking has become a barrier to understanding the
      biological causes of complex, multifactorial diseases characterized by clinical
      and therapeutic heterogeneity. Furthermore, not only is the flood of currently
      available medical and biological information highly heterogeneous, it is also
      often conflicting. Together with the entire absence of functional models of
      pathogenesis and pathological evolution of complex diseases, this leads to a
      situation where illness activity cannot be coherently approached and where
      therapeutic developments become highly problematic. Acquisition of the necessary
      knowledge can be obtained, in parts, using in silico models produced through
      analytical approaches and processes collectively known as 'Systems Biology'.
      However, without analytical approaches that specifically incorporate the facts
      that all that is called 'information' is not necessarily useful nor utilisable
      and that all information should be considered as a priori suspect, modelling
      attempts will fail because of the much too numerous conflicting and, although
      correct in molecular terms, physiologically invalid reports. In the present
      essay, we suggest means whereby this body of problems could be functionally
      attacked and describe new analytical approaches that have demonstrated their
      efficacy in alleviating these difficulties.

PMID- 30092387
TI  - The influence of Fe2+, Fe3+ and magnet powder (Fe3O4) on aerobic granulation and
      their mechanisms.
AB  - This study aimed to develop an aerobic granular sludge and understand the
      granulation process of the multi-iron ions. Four sequencing batch reactors (SBRs)
      were applied to elucidate the effect of Fe2+, Fe3+ and Fe3O4 addition on aerobic
      granulation. The results confirmed that the start-up time of aerobic granulation
      with Fe3O4 addition (11 days) was notably less than that with Fe2+ (16 days) and
      Fe3+ (27 days) addition. Larger granules achieved with Fe3O4 addition with a
      sludge volume index (SVI30) of 28.50 mL/g and settling velocity of 49.68 m/h.
      Scanning electron microscope (SEM) analysis further revealed that the presence of
      mineral crystal in the granule core with Fe2+ and Fe3O4 addition accelerated the
      granule formation and maintained the stability of the structure. Extracellular
      polymeric substances (EPS) were studied using three-dimensional-excitation
      emission matrix (3D-EEM) fluorescence spectra technology to gain a comprehensive
      view of the interactions between EPS and Fe2+, Fe3+ and Fe3O4. Around 94.76% and
      97.68% removal rate was noted for COD and ammonia in the granulation process.
      Finally, the dominant functional species involved in biological nutrients removal
      and granule formation were identified by high throughput sequencing technology to
      assess the effects of Fe2+, Fe3+ and Fe3O4 to granule at the molecular level.

PMID- 30092388
TI  - Oral cadmium exposure affects skin immune reactivity in rats.
AB  - Skin can acquire cadmium (Cd) by oral route, but there is paucity of data
      concerning cutaneous effects of this metal. Cd acquired by oral route can affect
      skin wound healing, but the effect of Cd on other activities involved in skin
      homeostasis, including skin immunity, are not explored. Using the rat model of 30
      day oral administration of Cd (5 ppm and 50 ppm) in drinking water, basic aspects
      of immune-relevant activity of epidermal cells were examined. Dose-dependent Cd
      deposition in the the skin was observed (0.035 +/- 0.02 ug/g and 0.127 +/- 0.04
      ug/g at 5 ppm and 50 ppm, respectively, compared to 0.012 +/- 0.009 ug/g at 0 ppm
      of Cd). This resulted in skin inflammation (oxidative stress at both Cd doses and
      dose-dependent structural changes in the skin and the presence/activation of
      innate immunity cells). At low Cd dose inflammatory response (nitric oxide and IL
      1beta) was observed. Other inflammatory cytokines (IL-6 and TNF) response
      occurred at 50 ppm, which was increased further following skin sensitization with
      contact allergen dinitro-chlorobenzene (DNCB). Epidermal cells exposed to both Cd
      doses enhanced concanavalin A (ConA)-stimulated lymphocyte production of IL-17.
      This study showed for the first time the effect of the metal which gained access
      to the skin via gut on immune reactivity of epidermal cells. Presented data might
      be relevant for the link between dietary Cd and the risk of skin pathologies.

PMID- 30092390
TI  - Development of in situ optical-electrical MEMS platform for semiconductor
      characterization.
AB  - In situ transmission electron microscopy (TEM) technology has become one of the
      fastest growing areas in TEM research in recent years. This technique allows
      researchers to investigate the dynamic response of materials to external stimuli
      inside the microscope. Optoelectronic functional semiconducting materials play an
      irreplaceable role in several key fields such as clean energy, communications,
      and pollution disposal. The ability to observe the dynamic behavior of these
      materials under real working conditions using advanced TEM technologies would
      provide an in-depth understanding of their working mechanisms, enabling further
      improvement of their properties. In this work, we designed a
      microelectromechanical-system-chip-based system to illuminate a sample inside a
      transmission electron microscope. This system allows simultaneous in situ optical
      and electrical measurements, which are crucial for optoelectronic semiconductor
      characterization.

PMID- 30092389
TI  - Cytotoxicity and enzymatic biomarkers as early indicators of benthic responses to
      the soluble-fraction of diesel oil.
AB  - Xenobiotics from oil tanker leaks and industrial discharges are amongst the main
      human impacts to confined coastal areas. We assessed the genotoxic responses to
      the water-soluble fraction of diesel oil in the polychaete Laeonereis culveri and
      the bivalve Anomalocardia flexuosa, two widespread benthic species in subtropical
      estuaries from the Southwestern Atlantic. We hypothesized that the highest
      responsiveness would be expressed by significantly different biomarkers responses
      between control and oil-impacted treatments. Responsiveness to diesel oil was
      investigated using an experimental design with two fixed factors (contaminant
      percentages and times of exposure). After exposure, we monitored the responses of
      the oxidative stress enzymes and performed micronuclei tests. Results were
      congruent for both species. Antioxidant defense of glutathione S-transferase and
      the induction of micronuclei and nuclear buds, the latter just for the bivalve,
      were significantly affected by polycyclic aromatic hydrocarbons, with significant
      increases on the seventh day of exposure and in the higher concentrations,
      compared to controls groups. We assessed the benefits and drawbacks of using each
      biomarker in laboratory experiments. Both species are indicators of early, and
      rapid responses to genotoxic contaminants in subtropical estuarine habitats. We
      suggest that the micronuclei frequency in A. flexuosa is a simple, fast and cheap
      test for genotoxicity in oil-impacted areas. Such early biomarkers are needed to
      develop better protocols for impact assessment and monitoring under real field
      conditions.

PMID- 30092391
TI  - Wavelet transform-based electron tomography measurement of buried interface
      roughness.
AB  - Interface roughness is a critical parameter determining the performance of
      semiconductor devices. We show that a continuous wavelet transform is useful to
      describe not only the magnitude of the interface roughness, but also the spatial
      frequencies that describe the interface. We propose a simple presentation of the
      results that makes it convenient to compare between interfaces. In particular, an
      average and maximum value wavelet profile that is obtained from a series of one
      dimensional wavelet transforms provides a traceable and quick survey of the
      results. We demonstrate the wavelet transform method using both computer
      simulations and by applying it to experimental data obtained by electron
      tomography of a test sample and to a molecular layer interface. Wavelet
      descriptions of the interface roughness suffers less from the presence of shot
      noise in the experimental data than the traditional root mean square error
      description of interface roughness. An increase in lateral dimensions of an
      interface that has large features increases the content of low spatial
      frequencies in wavelet transforms. In comparison, the value of root mean square
      error increases in an untraceable manner with the same increase in lateral
      dimensions on the same interface. Morse wavelets with gamma = 9 and beta = 3
      appear to be a suitable choice for applications in interface roughness
      measurement.

PMID- 30092392
TI  - On the effect of local sample slope during modulus measurements by contact
      resonance atomic force microscopy.
AB  - Contact-resonance atomic force microscopy (CR-AFM) is of great interest and very
      valuable for a deeper understanding of the mechanics of biological materials with
      moduli of at least a few GPa. However, sample surfaces can present a high
      topography range with significant slopes, where the local angle can be as large
      as  +/- 50 degrees . The non-trivial correlation between surface slope and CR
      frequency hinders a straight-forward interpretation of CR-AFM indentation modulus
      measurements on such samples. We aim to demonstrate the significant influence of
      the surface slope on the CR-frequency that is caused by the local angle between
      sample surface and the AFM cantilever and present a practical method to correct
      the measurements. Based on existing analytical models of the effect of the AFM
      set-up's intrinsic cantilever tilt on CR-frequencies, we compute the non-linear
      variation of the first two (eigen)modes CR-frequency for a large range of surface
      angles. The computations are confirmed by CR-AFM experiments performed on a
      curved surface. Finally, the model is applied to directly correct contact modulus
      measurements on a durum wheat starch granule as an exemplary sample.

PMID- 30092393
TI  - A method for site-specific and cryogenic specimen fabrication of liquid/solid
      interfaces for atom probe tomography.
AB  - A site-specific, cryogenic, focused ion beam (FIB) method is presented for the
      preparation of atom probe tomography (APT) specimens from a frozen liquid/solid
      interface. As a practical example, the interface between water and a corroded
      boroaluminosilicate glass has been characterized by APT for the first time. The
      water/glass interface is preserved throughout specimen preparation by plunge
      freezing the corroding glass particles with the corrosion solution into slush
      nitrogen. Site-specific specimen preparation is enabled through a new approach to
      extract and mount a small volume of material using a cryogenically cooled FIB
      stage and micromanipulator. The prepared APT specimens are subsequently
      transferred from the FIB to APT under cryogenic and high-vacuum conditions using
      a novel FIB/APT transfer shuttle and home-built environmental transfer hub
      attached to the APT system. Particular focus is given to the technical methods
      for specimen fabrication under cryogenic conditions. Persistent challenges are
      discussed in addition to future opportunities for this new specimen preparation
      method.

PMID- 30092394
TI  - A comparison of kinetics in the lower limbs between baseball tee and pitched ball
      batting.
AB  - In this study, the kinetic characteristics of lower limbs during batting were
      investigated by comparing batting off a tee with batting a pitched ball.
      Participants were 10 male collegiate baseball players who performed tee batting
      (TB) and batting using a pitching machine (MB; approximate ball speed: 33.3 m/s).
      Three-dimensional coordinate data were acquired using a motion capture system,
      and ground reaction forces were measured using three force platforms. Lower limb
      joint torques were obtained by inverse dynamics calculations. The results
      indicated that the angular velocity of the lower trunk was larger in TB than in
      MB for rotation. The swing time from stride foot contact with the ground to ball
      impact was significantly longer in MB than in TB. The angular impulses of
      bilateral hip adduction, pivot hip external rotation, and stride hip and knee
      extension torques were significantly larger in MB, suggesting that batters exert
      these joint torques earlier for pitched balls to handle time constraints by
      changing the rotation of the lower trunk in response to the unknown ball location
      and speed in MB. These findings will help to fill a gap in the literature and
      provide coaching insights for improving batting motion.

PMID- 30092396
TI  - Effects of treadmill running velocity on lower extremity coordination variability
      in healthy runners.
AB  - With a growing interest in coordination variability and its role in endurance
      running, it is important to identify the effect of running velocity. The purpose
      of the current study was to investigate the effect of treadmill running velocity
      on the coordination and variability of coordination of lower extremity couplings
      of healthy runners during stance. Fourteen apparently healthy runners ran on a
      split-belt force instrumented treadmill at five different velocities. Continuous
      relative phase (CRP) was used to quantify coordination and variability (vCRP)
      between lower extremity couplings of the right limb (thigh-shank, thigh-foot,
      shank-foot) during three phases of stance (loading, mid stance, and propulsion).
      Multiple one-way repeated measure ANOVAs were conducted to identify differences
      among velocity conditions at each phase and discrete events (initial foot
      contact, peak knee flexion during stance, and toe-off). Thigh internal/external
      rotation (IR/ER)-Shank abduction/adduction (AB/AD) coupling was different during
      the propulsive phase (p = 0.02). Thigh flexion/extension-Shank flexion/extension
      showed the greatest differences in vCRP across velocity conditions with
      differences occurring during loading phase, mid stance, propulsive phase, and
      peak flexion (p < 0.05). Additionally, significant differences were seen in Thigh
      FL/EX-Shank FL/EX (toe-off, p = 0.01) and Thigh FL/EX-Foot inversion/eversion
      (IN/EV) (toe-off, p = 0.032). Interestingly, the decreases in vCRP values were
      accompanied by changes in center of mass vertical motion during stance, but not
      knee flexion angles. Increases in running velocity led to a more constrained
      running pattern through a reduction in degrees of freedom.

PMID- 30092395
TI  - Priming of complex action via movement contingent sensory effects.
AB  - OBJECTIVES: The aim of the present study was to examine whether movement
      contingent sensory effects could be used to prime and facilitate motor
      performance on a ball-tossing task. DESIGN: The ball-tossing task was performed
      across two consecutive days, and consisted of an acquisition phase and a test
      phase. During the acquisition phase, participants (N = 30) practiced an
      underhanded ball tossing task to a near and far target (N = 360 total, n = 180
      each distance). Tosses that landed near the target immediately produced an
      auditory feedback tone upon landing, with unique tones for both the near and far
      target. In the test phase, the auditory tones preceded the toss and served as
      imperative stimuli for the tossing task. METHOD: The test phase consisted of
      three tossing conditions (corresponding, non-corresponding, and control) in which
      the participants responded to the tones by tossing the ball to either the
      corresponding or non-corresponding target associated with the tones during
      learning. RESULTS: Findings indicated that both accuracy and consistency of ball
      tossing improved when the toss was preceded by the corresponding auditory
      feedback associated with the successful execution of the action during learning.
      CONCLUSIONS: The present study extends previous research by showing that complex
      actions consisting of multiple degrees of freedom can be primed via movement
      contingent sensory effects. Furthermore, this study demonstrates that movement
      effect priming can impact distal measures of motor performance (e.g., accuracy of
      tossing), as opposed to the features of movement production (e.g., response
      selection, initiation, and execution).

PMID- 30092397
TI  - On the validity of several previously published perturbation formulas for the
      acoustoelastic effect on Rayleigh waves.
AB  - This article revisits the evaluation by a perturbation theory of the modification
      of the Rayleigh wave velocity under a static loading varying with depth. Two
      derivations, that have been exposed in the past and presented as comparable, are
      questioned. A new derivation of the perturbation formula is given by adapting
      Auld's approach. Validation with exact calculations is provided. The examples
      cover depth-varying static stress as well as depth-varying third order elastic
      properties.

PMID- 30092398
TI  - Towards an automated multimodal clinical decision support system at the post
      anesthesia care unit.
AB  - BACKGROUND: The aim of this study was to develop a predictive algorithm detecting
      early signs of deterioration (ESODs) in the post anesthesia care unit (PACU),
      thus being able to intervene earlier in the future to avoid serious adverse
      events. The algorithm must utilize continuously collected cardiopulmonary vital
      signs and may serve as an alternative to current practice, in which an alarm is
      activated by single parameters. METHODS: The study was a single center,
      prospective cohort study including 178 patients admitted to the PACU after major
      surgical procedures. Peripheral blood oxygenation, arterial blood pressure,
      perfusion index, heart rate and respiratory rate were monitored continuously.
      Potential ESODs were automatically detected and scored by two independent experts
      with regards to the severity of the observation. Based on features extracted from
      the obtained measurements, a random forest classifier was trained, classifying
      each event being either an ESOD or not an ESOD. The algorithm was evaluated and
      compared to the automated single modality alarm system at the PACU. RESULTS: The
      algorithm detected ESODs with an accuracy of 92.2% (99% CI: 89.6%-94.8%),
      sensitivity of 90.6% (99% CI: 85.7%-95.5%), specificity of 93.0% (99% CI: 89.9%
      96.2%) and area under the receiver operating characteristic curve of 96.9% (99%
      CI: 95.3%-98.5%). The number of false alarms decreased by 85% (99% CI: 77%-93%)
      and the number of missed ESODs decreased by 73% (99% CI: 61%-85%) as compared to
      the currently used alarm system in the hospital. The algorithm was able to detect
      an ESOD in average 26.4 (99% CI: 1.1-51.7) minutes before the current single
      parameter system used in the PACU. CONCLUSION: In conclusion, the proposed
      biomedical classification algorithm, when compared to the currently used single
      parameter alarm system of the hospital, showed significantly increased
      performance in both detecting ESODs fast and classifying these correctly. The
      clinical effect of the predictive system must be evaluated in future trials.

PMID- 30092399
TI  - The effects of safranal, a constitute of saffron, and metformin on spatial
      learning and memory impairments in type-1 diabetic rats: behavioral and
      hippocampal histopathological and biochemical evaluations.
AB  - Safranal is one of saffron constituents and has antioxidant and neuroprotective
      properties. Metformin is used as an anti-diabetic drug. This study was planned to
      investigate the separate and combined treatment effects of safranal and metformin
      on diabetes-induced learning and memory impairments by behavioral and hippocampal
      histopathological and biochemical evaluations. Diabetes was induced by
      intraperitoneal injection of streptozotocin (STZ), treatments with safranal
      (0.025, 0.1 and 0.4 mg/kg), metformin (50 and 200 mg/kg), and a combination of
      low doses of this chemicals were initiated after confirmation of diabetes and
      continued for 37 days. Blood glucose concentration was measured before and on
      days 15, 25 and 35 after injection of streptozotocin. Learning and memory tested
      using Morris Water Maze (MWM) on days 40-45 and on day 45 hippocampal specimens
      were collected for determination of malodialdehyde (MDA), tumor necrosis factor
      alpha (TNF-alpha) and Caspase-3 levels and superoxide dismutase (SOD) activity.
      The hippocampus was also designed for light microscopy evaluation. Hyperglycemia,
      spatial learning and memory impairments, hippocampal neuron loss, increase of
      hippocampal MDA, TNF-alpha and caspase-3 levels and decrease of SOD activity were
      observed in diabetic rats. Safranal (0.1 and 0.4 mg/kg), metformin (200 mg/kg)
      and safranal (0.025 mg/kg) with metformin (50 mg/kg) improved the above-mentioned
      behavioral, histopathological and biochemical changes. Safranal and metformin and
      their combination improved learning and memory impairments in STZ-induced
      diabetic rats. Antioxidant, anti-inflammatory and antiapoptotic mechanisms might
      be involved. It is recommended that safranal be considered for diabetes
      management.

PMID- 30092400
TI  - The ACE 2 activator diminazene aceturate (DIZE) improves left ventricular
      diastolic dysfunction following myocardial infarction in rats.
AB  - Diminazene aceturate (DIZE) has been reported to enhance the catalytic efficiency
      of ACE-2 and presumably increases angiotensin 1-7 generation, interfering with
      cardiac remodeling after myocardial infarction (MI). Our aim was to investigate
      the chronic effects of DIZE on cardiac dysfunction post-MI. Male Wistar rats
      underwent myocardial infarction (MI) or SHAM surgery (SO) and were divided into
      groups treated with DIZE 15 mg/kg/day, s.c. or vehicle (Control). After 4 weeks,
      the hemodynamic variables were recorded by cardiac catheterism. Hearts were then
      arrested to obtain the left ventricular (LV) pressure-volume curves in situ.
      Cardiomyocyte hypertrophy and collagen content were determined by histology. DIZE
      prevented LV end-diastolic pressure increases in MI rats (MI: 26 +/- 3.3 vs. MI
      DIZE: 15 +/- 1.6 mmHg, P < 0.001) without a significant effect on LV systolic
      pressure (LVSP). Moreover, DIZE improved LV contractility (+dP/dt, MI: 3014 +/-
      161 vs. MI-DIZE: 3884 +/- 104 mmHg/s, P < 0.001) and relaxation (-dP/dt, MI: 
      2333 +/- 91 vs. MI-DIZE: -2798 +/- 120 mmHg/s, P < 0.05). Right ventricular SP
      was increased in the MI compared to that in the SO group (40 +/- 0.6 vs. 30 +/-
      1.2 mmHg; P < 0.01), and DIZE partially prevented this augmentation. LV stiffness
      was reduced in MI-DIZE compared with that in MI (0.64 +/- 0.01 vs. 0.78 +/- 0.02
      mmHg/mL; P < 0.01). DIZE treatment reduced the interstitial collagen content by
      18% in the surviving LV myocardium. Cardiomyocyte hypertrophy remained unaffected
      by DIZE treatment. Our findings show that chronic DIZE treatment post-MI
      attenuates the morphofunctional changes induced by MI in rats. The effects on LV 
      dP/dt, chamber stiffness and collagen content suggest this drug can be used as a
      therapeutic agent to reduce interstitial fibrosis and diastolic dysfunction after
      MI.

PMID- 30092401
TI  - Akebia saponin D reverses corticosterone hypersecretion in an Alzheimer's disease
      rat model.
AB  - BACKGROUND: Glucocorticoid hormones are implicated in the pathogenesis of
      Alzheimer's disease (AD) and other diseases including diabetes, hyperlipidemia,
      and osteoporosis. Akebia saponin D (ASD) possesses numerous pharmacological
      activities, including as an anti-AD, anti-hyperlipidemia, anti-diabetes, and anti
      osteoporosis agent. The anti-AD effect of ASD is possibly through its regulation
      of glucocorticoid levels. PURPOSE: The present study was undertaken to
      investigate the neuroprotective effects of ASD on Abeta25-35-induced cognitive
      deficits and to elucidate its underlying mechanism of action. METHODS: The AD rat
      model was established by an intracerebroventricular injection of Abeta25-35 into
      the lateral ventricles. Spatial learning and anxiety state were assessed by
      Morris water maze task and elevated plus-maze assay, respectively. The degree of
      hypertrophy of adrenal gland was analyzed using the viscera coefficient.
      Corticosterone and ACTH concentrations in the plasm were measured using
      biochemical assay kits. The activity of 11beta-hydroxysteroid dehydrogenase type
      1 (11beta-HSD1) in liver and groin fat pad was assessed by measuring cortisol
      production. RESULTS: Compared with the control group, AD rats displayed
      significant spatial learning and reference memory impairments, serious anxiety
      disorders, obvious hypertrophy of adrenal gland, elevated corticosterone and ACTH
      levels in the plasma, and increased 11beta-HSD1 activity in liver and groin fat
      pad. ASD could significantly ameliorate the memory deficits and anxiety symptoms,
      markedly reduce the viscera coefficient of adrenal gland, observably decrease
      corticosterone and ACTH concentrations, and showed no effect on the activity of
      11beta-HSD1. CONCLUSIONS: These results indicate that ASD might exert a
      significant neuroprotective effect on cognitive impairment, driven in part by
      reducing systemic corticosterone level by down-regulation of the hypothalamic
      pituitary-adrenal (HPA) axis.

PMID- 30092402
TI  - The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate
      Induced Colitis.
AB  - The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid
      based medicine has potential as a next-generation treatment, but it is rarely
      successful with IBD. The aim of this study was to establish a microRNA-based
      therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a
      supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of
      sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and
      restored inflammation because of dextran sulfate sodium (DSS)-induced colitis.
      RNA sequencing analysis revealed that miR-29a and miR-29b could inhibit the
      interferon-associated inflammatory cascade. Subcutaneous injection of sCA-miR-29b
      also potently inhibited inflammation, and it efficiently targeted CD11c+
      dendritic cells (DCs) among various types of immune cells in the inflamed mucosa.
      RT-PCR analysis indicated that the miR-29 RNAs in CD11c+ DCs suppressed the
      production of interleukin-6 (IL-6), transforming growth factor beta (TGF-beta),
      and IL-23 subunits in DSS-treated mice. This may inhibit Th17 differentiation and
      subsequent activation, which is critical in IBD pathogenesis. In vivo experiments
      using a non-natural artificial microRNA sequence revealed that targeting of DCs
      in the inflamed colon is an exceptional feature of sCA. This study suggests that
      sCA-miR-29s may open a new avenue in nucleic acid-based medicine for IBD
      treatment.

PMID- 30092403
TI  - Improved Lentiviral Gene Delivery to Mouse Liver by Hydrodynamic Vector Injection
      through Tail Vein.
AB  - Delivery of genes to mouse liver is routinely accomplished by tail-vein
      injections of viral vectors or naked plasmid DNA. While viral vectors are
      typically injected in a low-pressure and -volume fashion, uptake of naked plasmid
      DNA to hepatocytes is facilitated by high pressure and volumes, also known as
      hydrodynamic delivery. In this study, we compare the efficacy and specificity of
      delivery of vesicular stomatitis virus G glycoprotein (VSV-G) pseudotyped
      lentiviral vectors to mouse liver by a number of injection schemes. Exploiting in
      vivo bioluminescence imaging as a readout after lentiviral gene transfer, we
      compare delivery by (1) "conventional" tail-vein injections, (2) "primed"
      injections, (3) "hydrodynamic" injections, or (4) direct "intrahepatic"
      injections into exposed livers. Reporter gene activity demonstrate potent and
      targeted delivery to liver by hydrodynamic injections. Enhanced efficacy is
      confirmed by analysis of liver sections from mice treated with GFP-encoding
      vectors, demonstrating 10-fold higher transduction rates and gene delivery to
      ~80% of hepatocytes after hydrodynamic vector delivery. In summary, lentiviral
      vector transfer to mouse liver can be strongly augmented by hydrodynamic tail
      vein injections, resulting in both reduced off-target delivery and transduction
      of the majority of hepatocytes. Our findings pave the way for more effective use
      of lentiviral gene delivery in the mouse.

PMID- 30092406
TI  - Efficacy and safety of tacrolimus in Osserman grade III and Osserman grade IV
      Myasthenia Gravis.
AB  - OBJECTIVE: A retrospective observational cohort study was conducted to evaluate
      the efficacy and safety of tacrolimus in Osserman grade III and Osserman grade IV
      myasthenia gravis (MG) patients. PATIENTS AND METHODS: MG patients admitted to
      the First Affiliated Hospital of Guangzhou University of Chinese Medicine between
      June 2011 and January 2017 with grade III and grade IV according to the modified
      Osserman scale were recruited and received a telephone follow-up in September
      2017. Patients treated with tacrolimus plus prednisone were compared with those
      treated without tacrolimus. The efficacy of tacrolimus was assessed using MG
      activities of daily living (MG-ADL) score, Osserman classification, Myasthenia
      Gravis Foundation of America (MGFA) post intervention status (PIS), the number of
      hospitalizations, the number of myasthenic crises and deaths. The adverse drug
      effects of tacrolimus were monitored. RESULTS: A total of 124 patients were
      included. The tacrolimus group had a significantly lower MG-ADL score than the
      control group at follow-up (1.90 +/- 2.27vs 2.97 +/- 2.78, p = 0.029). The
      difference of MG-ADL score between baseline and after follow-up was significantly
      greater in the tacrolimus group than the control group (-7.20 +/- 2.95 vs -5.52
      +/- 2.91, p =  0.003). Fewer patients were hospitalized in the tacrolimus group
      (p =  0.011). The Osserman classification, MGFA PIS, the number of myasthenic
      crises and deaths did not differ significantly between the two groups. Nineteen
      patients in the tacrolimus group had adverse drug reactions, but no severe
      adverse effects appeared. CONCLUSION: Our study suggested that tacrolimus could
      be an effective and safe treatment for Osserman grade III and Osserman grade IV
      MG patients.

PMID- 30092404
TI  - A Novel lncRNA, LINC00460, Affects Cell Proliferation and Apoptosis by Regulating
      KLF2 and CUL4A Expression in Colorectal Cancer.
AB  - Emerging evidence has proven that long noncoding RNAs (lncRNAs) play important
      roles in human colorectal cancer (CRC) biology, although few lncRNAs have been
      characterized in CRC. Therefore, the functional significance of lncRNAs in the
      malignant progression of CRC still needs to be further explored. In this study,
      through analyzing TCGA RNA sequencing data and other publicly available
      microarray data, we found a novel lncRNA, LINC00460, whose expression was
      significantly upregulated in CRC tissues compared to adjacent normal tissues.
      Consistently, real-time qPCR results also verified that LINC00460 was
      overexpressed in CRC tissues and cells. Furthermore, high LINC00460 expression
      levels in CRC specimens were correlated with larger tumor size, advanced tumor
      stage, lymph node metastasis and shorter overall survival. In vitro and in vivo
      assays of LINC00460 alterations revealed a complex integrated phenotype affecting
      cell growth and apoptosis. Mechanistically, LINC00460 repressed Kruppel-like
      factor 2 (KLF2) transcription by binding to enhancer of zeste homolog 2 (EZH2).
      LINC00460 also functioned as a molecular sponge for miR-149-5p, antagonizing its
      ability to repress cullin 4A (CUL4A) protein translation. Taken together, our
      findings support a model in which the LINC00460/EZH2/KLF2 and LINC00460/miR-149
      5p/CUL4A crosstalk serve as critical effectors in CRC tumorigenesis and
      progression, suggesting new therapeutic directions in CRC.

PMID- 30092407
TI  - Significant association of TNF-alpha, but not other pro-inflammatory cytokines,
      single nucleotide polymorphisms with intervertebral disc degeneration in Iranian
      population.
AB  - OBJECTIVES: As the important role of inflammation in pathophysiology of
      intervertebral disc degeneration and inconsistency regarding the role of pro
      inflammatory cytokine genes SNPs, the current case-control study was designed to
      assess this in Iranian population. PATIENTS AND METHODS: The genomic DNA of
      peripheral leukocytes of 76 patients and 140 healthy controls were investigated
      to sequence 9 SNPs of pro-inflammatory cytokine genes of interleukin 1 (IL-1),
      interleukin 6 (IL-6), and Tumor Necrosis Factor alpha (TNF-alpha) family.
      RESULTS: 'GA' and 'GG' genotype of TNF-alpha -308 G/A SNP were significantly
      associated with IVDD. While 'GA' was 1.93 times more frequent in patients, the
      'GG' genotype was more common among healthy subjects (OR = 0.51, P = 0.03). The
      'G' allele of TNF-alpha -238 G/A was 2.51 times more common in IVDD patients
      while the 'A' genotype was more frequent in controls with odds ratio of 0.39 (P =
      0.001). Interestingly, the homozygote 'GG' genotype was 2.98 times more prevalent
      in patients (P = 0.001) while the 'GA' heterozygote genotype was more common in
      healthy individuals (OR = 0.34). The other investigated SNPs were not
      significantly associated with disease in this study population. CONCLUSION:
      Polymorphisms of pro-inflammatory cytokine genes could take part in IVDD
      pathophysiology as the result of alteration in their expression levels or
      structures. The current study indicated significant roles of TNF-alpha -308 G/A
      and TNF-alpha -238 G/A SNPs with IVDD among Iranian patients. However, this study
      did not show any significant association between IVDD and either of SNPs of IL-1
      and IL-6 genes.

PMID- 30092405
TI  - Intratracheal Administration of siRNA Dry Powder Targeting Vascular Endothelial
      Growth Factor Inhibits Lung Tumor Growth in Mice.
AB  - Inhalation therapy using small-interfering RNA (siRNA) is a potentially effective
      therapeutic strategy for lung cancer because of its high gene-silencing effects
      and sequence specificity. Previous studies reported that intratracheal
      administration of siRNA using pressurized metered dose inhalers or nebulizers
      could suppress tumor growth in murine lung metastatic models. Although dry powder
      inhalers are promising devices due to their low cost, good portability, and
      preservability, the anti-tumor effects of siRNA dry powder have not been
      elucidated. To evaluate the gene-silencing and anti-tumor effects of
      intratracheally delivered siRNA dry powder, vascular endothelial growth factor
      specific siRNA (VEGF-siRNA) dry powder was administered intratracheally to mice
      with metastatic lung tumors consisting of B16F10 melanoma cells or Lewis lung
      carcinoma cells. A single intratracheal administration of VEGF-siRNA dry powder
      reduced VEGF levels in both bronchoalveolar lavage fluid and lung tumor tissue.
      Furthermore, repeated intratracheal administration of VEGF-siRNA dry powder
      suppressed the number of visible metastatic foci on the lung surface and tumor
      area in lung tissues. Taken together, intratracheal administration of siRNA dry
      powder could be a novel therapeutic strategy for lung cancer through the
      suppression of specific genes expressed in lung tumor tissue.

PMID- 30092408
TI  - Glioblastoma and primary central nervous system lymphoma: Preoperative
      differentiation by using MRI-based 3D texture analysis.
AB  - OBJECTIVES: To investigate the diagnostic value of magnetic resonance imaging
      (MRI)-based 3D texture and shape features in the differentiation of glioblastoma
      (GBM) and primary central nervous system lymphoma (PCNSL). PATIENTS AND METHODS:
      A total of eighty-two patients, including sixty patients with GBM and twenty-two
      patients with PCNSL were followed up retrospectively from January 2012 to
      September 2017. MRI-based 3D texture and shape analysis were performed to
      evaluate the detectable differences between the two malignancies. The performance
      of machine-learning models was assessed. The Mann-Whitney U test and receiver
      operating characteristic (ROC) analysis were performed, and the corresponding
      sensitivity, specificity, accuracy, and area under the curve (AUC) were
      calculated. Ultimately, 60 GBM patients (33 males, 27 females; mean age 51.55 +/-
      13.58 years, range 8-74 years) and 22 PCNSL patients (14 males, 8 females; mean
      age 55.18 +/- 12.19 years, range 32-78 years) were included in this study. All
      the PCNSLs were of the diffuse large B-cell type, and all patients were
      immunocompetent. RESULTS: The variables Firstorder_Skewness, Firstorder_Kurtosis,
      and Ngtdm_Busyness, representing features extracted from contrast-enhanced T1
      weighted images, showed high discriminatory power. Firstorder_ Skewness was the
      best selected predictor for classification (AUC = 0.86), followed by
      Ngtdm_Busyness (AUC = 0.83) and Firstorder_Kurtosis (AUC = 0.80). The
      sensitivities and specificities ranged from 70.0% to 83.3% and from 71.4% to
      90.5%, respectively. Among three classification models, the naive Bayes
      classifier was superior overall, with a high AUC (0.90) and the best specificity
      (0.91). The support vector machine models provided the best sensitivity and
      accuracy (0.92 and 0.88, respectively). CONCLUSIONS: MRI-based 3D texture
      analysis has potential utility for preoperative discrimination of GBM and PCNSL.

PMID- 30092410
TI  - A systematic study of the class imbalance problem in convolutional neural
      networks.
AB  - In this study, we systematically investigate the impact of class imbalance on
      classification performance of convolutional neural networks (CNNs) and compare
      frequently used methods to address the issue. Class imbalance is a common problem
      that has been comprehensively studied in classical machine learning, yet very
      limited systematic research is available in the context of deep learning. In our
      study, we use three benchmark datasets of increasing complexity, MNIST, CIFAR-10
      and ImageNet, to investigate the effects of imbalance on classification and
      perform an extensive comparison of several methods to address the issue:
      oversampling, undersampling, two-phase training, and thresholding that
      compensates for prior class probabilities. Our main evaluation metric is area
      under the receiver operating characteristic curve (ROC AUC) adjusted to multi
      class tasks since overall accuracy metric is associated with notable difficulties
      in the context of imbalanced data. Based on results from our experiments we
      conclude that (i) the effect of class imbalance on classification performance is
      detrimental; (ii) the method of addressing class imbalance that emerged as
      dominant in almost all analyzed scenarios was oversampling; (iii) oversampling
      should be applied to the level that completely eliminates the imbalance, whereas
      the optimal undersampling ratio depends on the extent of imbalance; (iv) as
      opposed to some classical machine learning models, oversampling does not cause
      overfitting of CNNs; (v) thresholding should be applied to compensate for prior
      class probabilities when overall number of properly classified cases is of
      interest.

PMID- 30092409
TI  - Dendrite morphogenesis from birth to adulthood.
AB  - Dendrites are the conduits for receiving (and in some cases transmitting) neural
      signals; their ability to do these jobs is a direct result of their morphology.
      Developmental patterning mechanisms are critical to ensuring concordance between
      dendritic form and function. This article reviews recent studies in vertebrate
      retina and brain that elucidate key strategies for dendrite functional
      maturation. Specific cellular and molecular signals control the initiation and
      elaboration of dendritic arbors, and facilitate integration of young neurons into
      particular circuits. In some cells, dendrite growth and remodeling continues into
      adulthood. Once formed, dendrites subdivide into compartments with distinct
      physiological properties that enable dendritic computations. Understanding these
      key stages of dendrite patterning will help reveal how circuit functional
      properties arise during development.

PMID- 30092411
TI  - A randomized controlled crossover trial evaluating differential responses to
      antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity:
      The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative
      Markers in HYpertension program-AIM-HY INFORM trial.
AB  - BACKGROUND: Ethnicity, along with a variety of genetic and environmental factors,
      is thought to influence the efficacy of antihypertensive therapies. Current UK
      guidelines use a "black versus white" approach; in doing so, they ignore the
      United Kingdom's largest ethnic minority: Asians from South Asia. STUDY DESIGN:
      The primary purpose of the AIM-HY INFORM trial is to identify potential
      differences in response to antihypertensive drugs used as mono- or dual therapy
      on the basis of self-defined ethnicity. A multicenter, prospective, open-label,
      randomized study with 2 parallel, independent trial arms (mono- and dual
      therapy), AIM-HY INFORM plans to enroll a total of 1,320 patients from across the
      United Kingdom. Those receiving monotherapy (n = 660) will enter a 3-treatment
      (amlodipine 10 mg od; lisinopril 20 mg od; chlorthalidone 25 mg od), 3-period
      crossover, lasting 24 weeks, whereas those receiving dual therapy (n = 660) will
      enter a 4-treatment (amlodipine 5 mg od and lisinopril 20 mg od; amlodipine 5 mg
      od and chlorthalidone 25 mg od; lisinopril 20 mg od and chlorthalidone 25 mg od;
      amiloride 10 mg od and chlorthalidone 25 mg od), 4-period crossover, lasting 32
      weeks. Equal numbers of 3 ethnic groups (white, black/black British, and
      Asian/Asian British) will ultimately be recruited to each of the trial arms (ie,
      220 participants per ethnic group per arm). Seated, automated, unattended,
      office, systolic blood pressure measured 8 weeks after each treatment period
      begins will serve as the primary outcome measure. CONCLUSION: AIM-HY INFORM is a
      prospective, open-label, randomized trial which aims to evaluate first- and
      second-line antihypertensive therapies for multiethnic populations.

PMID- 30092413
TI  - Rationale and design of: A Randomized tRial of Expedited transfer to a cardiac
      arrest center for non-ST elevation out-of-hospital cardiac arrest: The ARREST
      randomized controlled trial.
AB  - BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is a global public health
      issue. There is wide variation in both regional and inter-hospital survival rates
      from OHCA and overall survival remains poor at 7%. Regionalization of care into
      cardiac arrest centers (CAC) improves outcomes following cardiac arrest from ST
      elevation myocardial infarction (STEMI) through concentration of services and
      greater provider experience. The International Liaison Committee on Resuscitation
      (ILCOR) recommends delivery of all post-arrest patients to a CAC, but that
      randomized controlled trials are necessary in patients without ST elevation
      (STE). METHODS/DESIGN: Following completion of a pilot randomized trial to assess
      safety and feasibility of conducting a large-scale randomized controlled trial in
      patients following OHCA of presumed cardiac cause without STE, we present the
      rationale and design of A Randomized tRial of Expedited transfer to a cardiac
      arrest center for non-ST elevation OHCA (ARREST). In total 860 patients will be
      enrolled and randomized (1:1) to expedited transfer to CAC (24/7 access to
      interventional cardiology facilities, cooling and goal-directed therapies) or to
      the current standard of care, which comprises delivery to the nearest emergency
      department. Primary outcome is 30-day all-cause mortality and secondary outcomes
      are 30-day and 3-month neurological status and 3, 6 and 12-month mortality.
      Patients will be followed up for one year after enrolment. CONCLUSION: Post
      arrest care is time-critical, requires a multi-disciplinary approach and may be
      more optimally delivered in centers with greater provider experience. This trial
      would help to demonstrate if regionalization of post-arrest care to CACs reduces
      mortality in patients without STE, which could dramatically reshape emergency
      care provision.

PMID- 30092412
TI  - Association between neighborhood-level socioeconomic deprivation and incident
      hypertension: A longitudinal analysis of data from the Dallas heart study.
AB  - BACKGROUND: Cardiovascular disease is a leading economic and medical burden in
      the United States (US). As an important risk factor for cardiovascular disease,
      hypertension represents a critical point of intervention. Less is known about
      longitudinal effects of neighborhood deprivation on blood pressure outcomes,
      especially in light of new hypertension guidelines. METHODS: Longitudinal data
      from the Dallas Heart Study facilitated multilevel regression analysis of the
      relationship between neighborhood deprivation, blood pressure change, and
      incident hypertension over a 9-year period. Factor analysis explored neighborhood
      perception, which was controlled for in all analyses. Neighborhood deprivation
      was derived from US Census data and divided into tertiles for analysis.
      Hypertension status was compared using pre-2017 and 2017 hypertension guidelines.
      RESULTS: After adjusting for covariates, including moving status and residential
      self-selection, we observed significant associations between residing in the more
      deprived neighborhoods and 1) increasing blood pressure over time and 2) incident
      hypertension. In the fully adjusted model of continuous blood pressure change,
      significant relationships were seen for both medium (SBP: beta = 4.81, SE = 1.39,
      P = .0005; DBP: beta = 2.61, SE = 0.71, P = .0003) and high deprivation (SBP:
      beta = 7.64, SE = 1.55, P < .0001; DBP: beta = 4.64, SE = 0.78, P < .0001). In
      the fully adjusted model of incident hypertension, participants in areas of high
      deprivation had 1.69 higher odds of developing HTN (OR 1.69; 95% CI 1.02, 2.82),
      as defined by 2017 hypertension guidelines. Results varied based on definition of
      hypertension used (pre-2017 vs. 2017 guidelines). CONCLUSION: These findings
      highlight the potential impact of adverse neighborhood conditions on
      cardiometabolic outcomes, such as hypertension.

PMID- 30092414
TI  - School racial composition and lifetime non-medical use of prescription
      painkillers: Evidence from the national longitudinal study of adolescent to adult
      health.
AB  - OBJECTIVE: To investigate the possible effects of middle and high school racial
      composition on later reporting of lifetime non-medical use of prescription
      painkillers (NMUPP) in young adulthood, and to explore whether there is evidence
      of variability by individual race/ethnicity in such effects. METHODS: Using data
      from Wave 1 (1994/5) of the National Longitudinal Study of Adolescent to Adult
      Health (Add Health), we categorized the sample's 52 middle schools and 80 high
      schools as majority (>50%) non-Hispanic white, majority non-Hispanic black, or
      neither. We used two-level hierarchical modeling to explore associations between
      individual- and school-level race at Wave 1 and lifetime prescription painkiller
      misuse reported at Wave 4. We included a cross-level interaction between
      individual race and school racial composition to assess variability in school
      level associations by race. RESULTS: Overall crude prevalence of lifetime NMUPP
      in majority white schools (17.9%) was over three times that of prevalence in
      majority black schools (4.8%), and also higher than prevalence in schools neither
      predominantly black nor predominantly white (12.4%). Lifetime misuse among blacks
      in majority white schools was more prevalent (5.2%) than among blacks in black
      schools (2.8%), as was misuse among whites in white schools (19.3%) compared to
      their white peers in black schools (15.7%). Two-level random intercept Poisson
      regression results suggest that attendance in a majority black secondary school
      lowered a participant's risk of lifetime NMUPP (compared to attending a majority
      white school: RR=0.66, p = 0.03). Compared to blacks in black schools, blacks in
      white schools had twice the risk of prescription painkiller misuse (p = 0.004)
      over a decade later, and whites in white schools had 5.5 times the risk (p =
      0.01). The risk ratio comparing whites in black schools to whites in white
      schools was not significant (RR: 1.30; p = 0.37). CONCLUSIONS: We found evidence
      of an effect of school racial composition on the risk of misusing prescription
      painkillers over a decade later, over and above individual race, with higher risk
      of misuse reported among participants who had attended white schools. Black
      participants who had attended predominantly white schools were, on average, twice
      as likely to report lifetime misuse of prescription painkillers compared to
      blacks who had attended black schools.

PMID- 30092415
TI  - Physcion 8-O-beta-glucopyranoside exhibits anti-leukemic activity through
      targeting sphingolipid rheostat.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common fatal cancer in
      people younger than 20 years of age. This study was designed to explore the anti
      leukemia activity of physcion 8-O-beta-glucopyranoside (PG) in B-cell ALL.
      METHODS: NALM6 and SupB15 cells were used as model cell lines. Cell viability,
      cell apoptosis, cell cycle distribution were determined by CCK-8 assay, DNA
      fragmentation assay and flow cytometry, and flow cytometry, respectively.
      Expression of proteins involved in cell apoptosis and cell cycle regulation was
      determined by western blot and the levels of ceramide and sphingosine 1-phosphate
      (S1P) were determined by ELISA. Activity of sphingosine kinase 1 (SphK1) was also
      determined with a Sphingosine Kinase Assay Kit. In the present study, both model
      cell lines were transfected with siRNA targeting SphK1 or an overexpression
      plasmid to examine the role of SphK1 in the anti-leukemia activity of PG.
      Moreover, the efficacy of PG was examined in vivo in a mouse model by measuring
      survival and spleen weight. RESULTS: Our results provided experimental evidence
      that PG could significantly induce apoptosis and cell cycle arrest in vitro.
      Mechanistically, the anti-leukemia activity of PG was mediated by its ability to
      repress SphK1 and thus modulate ceramide-S1P rheostat. Moreover, the anti
      leukemia activity of PG was also verified in a murine model. CONCLUSION:
      Collectively, our results indicate that PG may be a promising agent for the
      treatment of B-cell leukemia.

PMID- 30092416
TI  - Kaempferol-induces vasorelaxation via endothelium-independent pathways in rat
      isolated pulmonary artery.
AB  - BACKGROUND: Kaempferol, a flavonoid, is the essential part of human diet.
      Flavonoids have different pharmacological activities like cardioprotective, anti
      inflammatory and anti-oxidant. The aim of current study was to investigate
      vasorelaxant potential of kaempferol on rat isolated pulmonary artery and to
      assess the underling mechanisms. METHODS: Tension experiments were conducted on
      both the branches of main pulmonary artery of rats. Experiments were done using
      isolated organ bath system by recording tension with the help of data acquisition
      system, Power Lab. RESULTS: Kaempferol (10-8-10-4.5M) caused concentration
      dependent relaxation (Emax 124.33+/-4.37%; pD2 5.03+/-0.084) of endothelium
      intact pulmonary artery. In endothelium-denuded arterial rings, relaxation
      produced by kaempferol was not different from intact artery. L-NAME,
      indomethacin, combination of L-NAME and indomethacin did not show any effect on
      kaempferol-induced relaxation. Kaempferol-induced relaxation was reduced (Emax
      55.53+/-7.72%) in 60mMK+ pre-contracted pulmonary arterial rings. Iberiotoxin
      significantly decreased (Emax 71.68+/-11.84%) the relaxation response. However,
      glibenclamide, BaCl2, 4-AP (1mM) and ICI182780 did not reduce the kaempferol
      induced relaxation. TEA (10mM) and 4-AP (5mM) significantly reduced relaxation.
      Kaempferol-induced relaxation was significantly attenuated (Emax 94.92+/-19.60%)
      in presence of ODQ. H89 significantly decreased (Emax, 98.38+/-8.55%) the
      kaempferol-induced relaxation in rat pulmonary arterial rings. HC067047 and
      apamin did not show any effect on kaempferol-induced relaxation. In endothelium
      denuded K+ (80mM)-depolarized arterial rings, kaempferol (10MUM) markedly reduced
      CaCl2-induced contractions (Emax 35.14+/-6.53% vs. control 69.04+/-15.19%).
      CONCLUSION: Kaempferol relaxes rat pulmonary artery in endothelium-independent
      manner through involvement of BKCa channel, sGC, PKA pathways and inhibition of
      Ca2+-influx through L-type calcium channels.

PMID- 30092417
TI  - Effects of simvastatin on nuclear receptors, drug metabolizing enzymes and
      transporters expression in Human Umbilical Vein Endothelial Cells.
AB  - BACKGROUND: Vascular endothelial cells (EC) are constantly exposed to endo- and
      exogenous compounds, which may disturb EC function. One of the protecting
      mechanisms against chemicals consists of drug metabolizing enzymes and
      transporter proteins regulated by nuclear receptors and transcription factors.
      Therefore, the aim of the current study was to assess the regulation of nuclear
      receptors and their coordinated genes in Human Umbilical Vein Endothelial Cells
      (HUVEC). METHODS: HUVEC were exposed to TCDD (10nM), oltipraz (100MUM) and
      simvastatin (1MUM) for 24h. Gene expressions were evaluated using quantitative
      real-time PCR. The protein expression levels were determined by Western blotting.
      Enzymatic activity of CYP1A1/CYP1B1 was assessed by luciferin-labelled CYPs
      substrate. RESULTS: Our study confirmed that nuclear receptor AhR and nuclear
      factor Nrf2 are highly expressed in HUVECs. Treatment of HUVECs with TCDD (AhR
      inducer) resulted in a significant induction of AHR target genes CYP1A1, CYP1B1
      and NQO1. Oltipraz (Nrf2 inducer) also markedly increased expression of NQO1 but
      did not affect Nrf2 mRNA nor protein levels. Under simvastatin stimulation PXR
      and NRF2 target transcripts were not altered, however AHR-regulated genes:
      CYP1A1, CYP1B1 and MDR1 were significantly induced. Western blot analysis
      confirmed CYP1B1 induction in TCDD-treated HUVECs, but not in the simvastatin
      group. Moreover, HUVEC exposure to TCDD resulted in induction of CYP1A1/CYP1B1
      enzymatic activity. CONCLUSIONS: This study revealed functional expression of AhR
      and Nrf2 in HUVECs. Moreover, it was defined that simvastatin induced AhR and its
      related genes.

PMID- 30092418
TI  - Effects of low and high doses of acetylsalicylic acid on penicillin-induced
      epileptiform activity.
AB  - BACKGROUND: The most common headache associated with epilepsy occurs after
      seizure activity and is called a postictal headache. Therefore, the objective of
      this study was to investigate the effects of low and high doses acetylsalicylic
      acid (aspirin) on a penicillin-induced experimental epilepsy model. METHODS:
      Adult male Wistar rats (n = 28, weighing 220 +/- 40 g) were used in the
      experiments. The rats were divided into four groups as Control, Penicillin,
      Aspirin 150 mg/kg, Aspirin 500 mg/kg. Seizure activity was triggered by an
      intracortical injection of penicillin G potassium (500 IU/2.5 MUl) into the
      sensory motor cortex. An electrocorticogram was recorded by using conductive
      screw electrodes. Aspirin at the doses of 500 mg/kg and 150 mg/kg was given
      intraperitoneally (ip) 30 min after penicillin administration. RESULTS:
      Anticonvulsant activity appeared at the 30th and 40th min after an
      intracortically administered injection of penicillin in the groups given aspirin
      doses of 500 mg/kg (ip) and 150 mg/kg (ip) respectively. The amplitude of
      epileptiform activity at both doses of aspirin decreased but the difference was
      not statistically significant. CONCLUSIONS: The results of the present study
      suggest that low and high doses of aspirin may decrease epileptiform activity in
      penicillin-induced epilepsy. Aspirin might be suggested for headache associated
      with epilepsy.

PMID- 30092419
TI  - Early Outcomes of Traumatic Femoral Artery Aneurysm (Open Repair versus
      Endovascular Treatment).
AB  - BACKGROUND: The goals of surgical treatment of traumatic femoral artery aneurysm
      (FAA) are to isolate and excise the aneurysm, prevent distal embolization, and
      allow effective revascularization. During recent years, endovascular surgery has
      become a valid alternative to open repair. We aimed to compare early outcomes of
      the stent graft in the treatment of traumatic FAA and open surgical procedures.
      METHODS: This was a prospective study on 20 patients admitted to our hospital
      during the period from April 2016 to September 2017 with specific criteria of
      traumatic FAA. The patients were randomly divided into 2 groups with a one to one
      ratio between open repair (group I) and endovascular therapy (group II). We used
      the duplex scan in early follow-up 1 week and 1 month and 3 months
      postoperatively. RESULTS: Twenty FAAs were treated as follows: Excision of the
      aneurysm in patients of group I and repair by primary sutures or bypass with no
      graft failure occurred intraoperatively. Ten stents were placed in ten FAAs in
      group II. An early patency rate of 100% in 1 week was found in both groups, and
      thrombosis in 1 stent graft occurred after 1 month and 3 months (95%). The mean
      time of surgical operations was 107.5 min, and the mean time of endovascular
      procedures was 85 min. The group I had a significantly longer mean hospital stay
      time (8 days) than group II (4.25 days); P value < 0.05. CONCLUSIONS: FAA
      treatment can be performed easily and safely by surgery or endovascular
      procedures. Although the endovascular approach has several advantages, the
      incidence of thrombosis and high cost of stent grafts should be considered.

PMID- 30092420
TI  - A Case of Intravenous Leiomyomatosis with Involvement of a Renal Vein.
AB  - Our patient is a 44-year-old woman who underwent exploratory laparotomy with
      total abdominal hysterectomy and bilateral salpingo-oophorectomy by gynecologic
      oncology for a suspected malignancy. The diagnosis of intravenous leiomyomatosis
      (IVL) was made instead. She was followed by her gynecologist and remained
      asymptomatic until 2 years later when she complained to the GYN of leg heaviness,
      and 2 months later also complained of palpitations. She was treated with a short
      course of megestrol without any clinical response. She was then referred to
      Vascular Surgery. A computed tomography scan of the abdomen and pelvis with
      intravenous contrast demonstrated intraluminal lesions in the inferior vena cava
      (IVC) extending to the mid-portion of the retrohepatic vena cava and into the
      left renal vein which could be followed to the blind end of the remnant of the
      left gonadal vein. Transabdominal resection was performed via a midline incision
      with reflection of the right colon and hepatic flexure to the left in conjunction
      with a Kocher maneuver and mobilization of the liver anteriorly, exposing the IVC
      from the bifurcation to the hepatic veins. Tumor inside the IVC could be palpated
      extending from the point of origin of the remnant of the right gonadal vein to
      below the level of the hepatic veins. The most superior portion of the tumor was
      mobile inside the IVC and was milked down to just above the renal veins. Control
      was obtained below and above the tumor as well as of the bilateral renal veins
      and lumbars. The patient was given systemic anticoagulation and after 3 min blood
      flow was interrupted. The IVC was opened via a longitudinal venotomy. The segment
      into the left renal vein could not be removed, and the left renal vein was
      amputated leaving a blind segment in the left renal vein without connection to
      the central venous circulation. The tumor originated inferiorly from the remnant
      of the right gonadal vein, and the venotomy was extended inferiorly to encircle
      the origin of the right gonadal vein. The remnant of the right gonadal vein was
      then resected en-masse with the tumor and a small island of IVC around it. The
      venotomy in the IVC was then closed. On follow-up, the patient is asymptomatic
      and without radiographic evidence of recurrence 22 months after surgery. On
      planning for resection of IVL, it is of critical importance to consider the
      proximal and distal extent of the tumor, but also the various routes through
      which the tumor may reach the central venous circulation, to include the
      bilateral hypogastric veins, the right gonadal vein, and the left renal vein via
      the left gonadal vein.

PMID- 30092421
TI  - The Role of May-Thurner Syndrome in Recurrent Thrombosis after Catheter-Directed
      Thrombolysis of Deep Vein Thrombosis.
AB  - BACKGROUND: May-Thurner syndrome (MTS) leads to an increased incidence of deep
      vein thrombosis (DVT). Early thrombus removal decreases the post-thrombotic
      morbidities. Our aim was to better elucidate the relationship between MTS and
      venous patency after catheter-directed thrombolysis (CDT). METHODS: The medical
      records of all patients who underwent CDT from January 2005 to December 2011 due
      to acute DVT were reviewed retrospectively. Patient characteristics and clinical
      variables were evaluated to determine association with vein patency. RESULTS: A
      total of 51 male and 31 female with a mean age of 34.9 years were treated with
      CDT. During a median follow-up of 91.7 months, primary patency and secondary
      patency of all patients were 79.3% and 87.3%, respectively. The presence of MTS
      was the only significant predictor factor of patency. CONCLUSIONS: The residual
      stenosis caused by MTS is a risk for recurrent DVT and should be treated with
      stenting to improve the outcome.

PMID- 30092423
TI  - Nationally Representative Readmission Factors Associated with Endovascular versus
      Open Repair of Abdominal Aortic Aneurysm.
AB  - BACKGROUND: Hospital readmissions are tied to financial penalties and thus
      significantly influence health-care policy. Many current studies on readmissions
      lack national representation by not tracking readmissions across hospitals. The
      recently released Nationwide Readmission Database is one of the most
      comprehensive national sources of readmission data available, making it an
      invaluable resource to understand this critically important health policy issue.
      METHODS: The Nationwide Readmission Database for 2013 and 2014 was queried for
      adult patients with abdominal aortic aneurysm (441.4) undergoing endovascular
      (39.71) or open (38.44) repair. Outcomes examined were overall/initial admission
      mortality and overall/30-day readmissions. Multivariate logistic regression for
      these outcomes was also performed on multiple readmission factors. RESULTS: Fifty
      three thousand four hundred seventeen patients underwent abdominal aortic
      aneurysm repair (47,431 endovascular aortic repair [EVAR] versus 5,986 open
      surgical repair [OSR]). Significant differences were found for EVAR versus OSR on
      overall readmissions, initial admission cost, readmission costs, length of stay,
      days to readmission, and overall/initial admission mortality. Multivariate
      logistic regression analysis found that length of stay > 30, Charlson Comorbidity
      Index > 1, discharge disposition, and female sex were all significant predictors
      of 30-day readmission. Repair type was significantly associated with 30-day
      readmissions; however, it was not a significant factor for overall readmissions.
      CONCLUSION: There are significant differences in costs, prognosis, and
      readmission rates for EVAR versus OSR. Given that these differences are being
      used to create "acceptable" readmission rates, disbursement quotas among
      hospitals, and subsequent penalties for providers outside the expected rates, it
      is only prudent to obtain the most accurate information to guide those policies.
      LEVEL OF EVIDENCE: Care management/epidemiological, level IV.

PMID- 30092422
TI  - The Use of the Carotid Sheath as a Rotation Anchor to Detect an Anomalous
      Ascending Pharyngeal Artery in Carotid Endarterectomy.
AB  - Carotid endarterectomy (CEA) requires complete control of the blood backflow. An
      anomalous ascending pharyngeal artery (AphA) has been reported to result in
      incomplete control of the blood flow during CEA. Here, we present a case of
      symptomatic right internal carotid stenosis for which CEA was performed. An
      anomalous AphA was confirmed based on its origin from the distal internal carotid
      artery (ICA) on 3-dimensional rotational angiography (3DRA). The anomalous AphA
      arose near the distal end of the plaque, and the origin of the AphA was located
      in the dorsal wall of the ICA, hidden from the surgical view. The origin of the
      AphA was detected with rotation of the ICA within the carotid sheath (CS).
      Intraoperatively, the blood flow from the AphA was completely controlled with
      clamping of the origin of the AphA. We emphasize the importance of the 3DRA to
      detect an anomalous AphA and propose the use of the CS as an anchor to rotate the
      ICA for optimizing the surgical view behind the ICA. This simple surgical
      technique facilitates to detect and clamp an anomalous AphA arising from the ICA.

PMID- 30092424
TI  - Hybrid Treatment of a True Right Subclavian Artery Aneurysm Involving the
      Vertebral Artery using a Covered Stent.
AB  - Subclavian artery aneurysms (SAAs) are rare but potentially life- and limb
      threatening. We present the case of a 69-year-old man with a true right SAA; the
      vertebral artery branched off the aneurysm and was the dominant one. A hybrid
      (combined open surgical and endovascular) repair was performed; the vertebral
      artery was anastomosed end to side to the common carotid artery through a right
      supraclavicular incision, then using a percutaneous high brachial artery access,
      a covered stent was deployed to exclude the SSA. The procedure was technically
      successful, and computed tomography angiography at 24 months showed regular
      placement of the endograft with blood flow within it and absence of any endograft
      related complication (i.e., stent fracture/thrombosis/displacement or any-type
      detectable endoleak). This hybrid treatment is safe and feasible with good
      midterm results and may represent a valuable, less invasive alternative to
      conventional open surgical approaches.

PMID- 30092425
TI  - Ruptured Profunda Femoris Artery Aneurysm: A Case Report.
AB  - Aneurysms of the profunda femoris artery (PFA) are exceptionally rare but
      dreadful because of their high rate of rupture. In this report, we describe the
      case of a 70-year-old man presented to the emergency department with a ruptured
      PFA aneurysm. The patient underwent successful aneurysmorrhaphy and distal
      reconstruction with a vein graft.

PMID- 30092426
TI  - Treatment of Type I Endoleak after Thoracic Endovascular Aortic Repair and Stent
      Extension via False Lumen Catheterization and Coil Embolization.
AB  - Thoracic endovascular aortic repair (TEVAR) is a minimally invasive alternative
      to conventional open surgical reconstruction for the treatment of thoracic aortic
      dissection. However, the possibility of a type I endoleak may contribute to false
      lumen enlargement and rupture. Here, we present a case of successful treatment of
      type I endoleak after TEVAR and endograft extension for a complicated descending
      thoracic aortic dissection that was embolized by coils via a false lumen channel
      through the distal entry tear. This endovascular technology might offer a new
      option to treat thoracic type I endoleak by embolizing the blood entry site of
      the endoleak through the distal entry site and false lumen.

PMID- 30092427
TI  - Portal Vein Thrombosis after Endovascular Embolization of Splenic Artery for a
      Symptomatic Arterioportal Fistula: A Case Report and Literature Review.
AB  - Arterioportal fistula (APF) can induce severe portal hypertension and therefore
      requires appropriate and timely management. Endovascular treatment is
      increasingly used for the treatment of APFs due to its minimally invasive nature,
      although this procedure can lead to potentially fatal portal vein thrombosis
      (PVT). Reports of this complication are, however, rare. Here, we describe the
      case of a 65-year-old woman who experienced an extensive thrombosis from the
      splenic vein to the right portal vein after embolization of a splenic APF,
      leading to the requirement for intensive care unit care and a prolonged hospital
      stay. In addition, the literature was reviewed to describe the clinical
      manifestations, diagnosis, and treatment of PVT after embolization of APF.

PMID- 30092428
TI  - Unexpected Complication of a Nitinol-Constrained Balloon Angioplasty (Chocolate)
      in Rutherford Class 3 Patient Presenting Challenging Aorto-Iliac Anatomy.
AB  - We report an unusual complication of Chocolate nitinol-constraining structure
      after right superficial femoral artery (SFA) angioplasty. The procedure was
      performed by vascular surgeons in an operating theater equipped by a portable
      fluoroscopy unit. Under local anesthesia, by a contralateral approach, a 7F
      introducer sheath was advanced through the proximal portion of the right common
      iliac artery. Owing to the severe aorto-iliac vessels calcification, it was not
      possible to place the introducer sheath into a more distal vessel, as planned.
      After external iliac artery (EIA) stenting (7 * 80 mm Eluvia), SFA obstruction
      was intraluminal crossed, and a 6 * 120 mm nitinol-constrained balloon
      (Chocolate; Medtronic) was advanced in place and inflated. Once the balloon came
      out, the nitinol-constraining structure was not attached to the balloon surface.
      Under fluoroscopy, the crashed nitinol mesh was identified at distal edge of
      previously positioned EIA stent. To prevent mesh migration, it was fixed by
      covering with a 7 * 40 mm stent. The procedure was then successfully completed,
      as planned. One-month, postoperative computed tomography angiography showed
      complete expansion of the stents and no significant residual stenosis (>30%) in
      EIA, and SFA. Chocolate's mesh was still evident between the stent and the iliac
      artery wall, in absence of further complications. A 3 months follow-up, patient
      was still completely asymptomatic for claudication.

PMID- 30092429
TI  - Fusion Imaging for EVAR with Mobile C-arm.
AB  - BACKGROUND: Fusion imaging is a technique that facilitates endovascular
      navigation but is only available in hybrid rooms. The goal of this study was to
      evaluate the feasibility of fusion imaging with a mobile C-arm in a conventional
      operating room through the use of an angionavigation station. METHODS: From May
      2016 to June 2017, the study included all patients who underwent an aortic stent
      graft procedure in a conventional operating room with a mobile flat-panel
      detector (Cios Alpha, Siemens) connected to an angionavigation station (EndoNaut,
      Therenva). The intention was to perform preoperative 3D computerized
      tomography/perioperative 2D fluoroscopy fusion imaging using an automatic
      registration process. Registration was considered successful when the software
      was able to correctly overlay preoperative 3D vascular structures onto the
      fluoroscopy image. For EVAR, contrast dose, operation time, and fluoroscopy time
      (FT) were compared with those of a control group drawn from the department's
      database who underwent a procedure with a C-arm image intensifier. RESULTS: The
      study included 54 patients, and the procedures performed were 49 EVAR, 2 TEVAR, 2
      IBD, and 1 FEVAR. Of the 178 registrations that were initialized, it was possible
      to use the fusion imaging in 170 cases, that is, a 95.5% success rate. In the
      EVAR comparison, there were no difference with the control group (n = 103) for FT
      (21.9 +/- 12 vs. 19.5 +/- 13 min; P = 0.27), but less contrast agent was used in
      the group undergoing a procedure with the angionavigation station (42.3 +/- 22 mL
      vs. 81.2 +/- 48 mL; P < 0.001), and operation time was shorter (114 +/- 44 vs.
      140.8 +/- 38 min; P < 0.0001). CONCLUSIONS: Fusion imaging is feasible with a
      mobile C-arm in a conventional operating room and thus represents an alternative
      to hybrid rooms. Its clinical benefits should be evaluated in a randomized
      series, but our study already suggests that EVAR procedures might be facilitated
      with an angionavigation system.

PMID- 30092431
TI  - Open Repair for Juxtarenal Aortic Aneurysm: Short and Long-term Results.
AB  - BACKGROUND: The recent technological evolution has also allowed for the treatment
      of juxtarenal aortic aneurysm (JAA) with an endovascular technique, but short-
      and long-term results must be compared with the results of open treatment, which
      is the gold standard. In this study, we analyzed the short- and long-term results
      of open surgical treatment (open repair) in patients with JAA in our series.
      METHODS: From January 2006 to December 2016, 155 patients were treated for JAA
      with open repair; the data were analyzed retrospectively. The mean age was 71.17
      years (standard deviation [SD] 7.1), and mean size of aneurysm was 6.15 cm (SD
      1.1). The ASA classes 2, 3, and 4 were 20%, 74% and 6%, respectively. Follow-up
      included clinical visit and abdominal aorta Duplex scan after 1 and 6 months and
      annually. The mean follow-up interval was 48.6 (SD 32.4) months. RESULTS: The
      mean surgical time was 256 min (SD 69), the mean stay in the intensive care unit
      was 1.6 days (SD 1.2), and the mean total hospital stay was 10.2 days (SD 4.3).
      Aortic cross-clamping was usually suprarenal (110, 71%); in 39 (25%), the aortic
      clamping was between the renal arteries, and 6 patients (4%) required a
      supraceliac cross-clamping. The mean renal ischemia time due to aortic clamping
      was 17 min (SD 3.5). In 32 patients (21%), the left renal vein was sectioned for
      performing proximal aortic anastomosis and then reconstructed. Twelve patients
      (8%) required a renal revascularization, and in 49 patients (32%), an hypogastric
      bypass was performed. The 30-day mortality rate was 0.6%, and only 1 patient died
      in the postoperative due to intestinal infarction. The postoperative morbidities
      occurred in 15 cases (10%). Six patients had dehiscence of the laparotomy without
      the involvement of the muscle, 4 patients had an asymptomatic small increase of
      the troponin, and in 3 patients, there was an increase in creatinine >1.8 mg/dL.
      No dialysis was performed. Two patients had peripheral embolism in the lower
      limbs. Twenty-six patients (15%) died in the follow-up, but causes have never
      been related to aortic disease. CONCLUSIONS: Open repair of JAA is still safe,
      effective, and durable also in the long-term period and even in patients with
      multiple cardiovascular risk factors.

PMID- 30092430
TI  - Spontaneous Type Ia Endoleak Sealing in Patients Undergoing Endovascular Aneurysm
      Repair With the Ovation Stent Graft.
AB  - BACKGROUND: Type Ia endoleak may lead to continuous sac pressurization and late
      rupture after endovascular aneurysm repair (EVAR). Nevertheless, there have been
      scarce reports suggesting that these endoleaks may occasionally present
      spontaneous sealing. Taking into account the original sealing mechanism of the
      Ovation endograft that exploits 2 polymer-filled O-rings, we hypothesize that
      spontaneous type Ia endoleak sealing may sometimes incur following implantation
      of this device. We aim to report our experience with spontaneous type Ia endoleak
      sealing in patients treated with the Ovation endograft. METHODS: This is a
      retrospective observational study which included all patients undergoing EVAR
      with the Ovation endograft in a single institution during a 6-year period.
      Patients with an intraoperative type Ia endoleak were identified. The primary
      endpoint was rate of spontaneous sealing. Secondary endpoints were migration, sac
      expansion, need for reinterventions, secondary type Ia endoleaks, and aneurysm
      related and overall mortality. Adherence to the instructions for use (IFU) was
      evaluated to examine relation with occurrence of endoleak and rates of
      spontaneous sealing. RESULTS: Among 147 patients treated, 8 (5%) left the
      operation theater with a type Ia endoleak. In 6 patients, the endoleak
      spontaneously resolved during a maximum of 3 months of follow-up. Among those, 5
      cases were treated outside the IFU (2 short necks and 3 with severe angulation),
      while the sixth was a patient treated inside the IFU but was anticoagulated. In 2
      patients, the endoleak did not spontaneously resolve. One presented a conical
      neck of marginal length and the other circumferential calcifications. Type Ia
      endoleak was significantly more common among patients treated in an off-label
      fashion. CONCLUSIONS: Spontaneous sealing of type Ia endoleak is common after
      EVAR with the Ovation endograft. Nonadherence to the IFU results in more
      endoleaks, but it does not seem to reduce possibilities for spontaneous sealing.

PMID- 30092432
TI  - A Case of Acute Iliocaval Thrombosis in the Setting of a Suprarenal Inferior Vena
      Cava Saccular Aneurysm.
AB  - Inferior vena cava (IVC) aneurysms are a rare finding, whose management and
      outcomes remain uncertain due to their low incidence and long-term follow-up. As
      IVC aneurysms remain a poorly understood clinical entity, it is important to
      expand upon our existing knowledge base as new cases arise. We present a patient
      with a suprarenal IVC saccular aneurysm and an overview of the current literature
      regarding IVC aneurysm classification, presentation, and management. Based on the
      expanding literature, we propose that IVC aneurysms may be simplified into a 2
      type classification, which can further guide clinicians on management of the
      aneurysm.

PMID- 30092433
TI  - Outcomes of Stenting versus Endarterectomy for Symptomatic Extracranial Carotid
      Stenosis: A Retrospective Multicenter Study in Korea.
AB  - BACKGROUND: The present multicenter retrospective study aimed to compare the
      outcome of carotid artery stenting (CAS) versus carotid endarterectomy (CEA)
      among Korean patients with symptomatic extracranial carotid stenosis. METHODS:
      Between January 2008 and December 2011, 677 patients underwent either CAS (346,
      51.1%) or CEA (331, 48.9%). The primary end point included the occurrence of
      major adverse cardiovascular events (MACEs), defined as fatal or nonfatal stroke
      and myocardial infarction, and all-cause mortality during the periprocedural
      period and within 4 years after CAS or CEA. RESULTS: Although patients undergoing
      CAS and CEA did not differ significantly in MACE incidence within 4 years (15.3%
      vs. 11.5%, P = 0.14), CEA showed lower periprocedural MACE incidence than CAS
      with clinical significance (6.1% vs. 3.0%, P = 0.06). During the periprocedural
      period, the incidence of any stroke was significantly higher in patients
      undergoing CAS (5.5% vs. 2.4%, P = 0.04) but not the incidence of myocardial
      infarction (0.6% vs. 0.3%, P > 0.99). Kaplan-Meier survival analysis showed
      similar MACE-free (P = 0.16), stroke-free (P = 0.24), and overall survival (P =
      0.25) rates in both groups. On subgroup analysis, patients older than 70 years
      undergoing CAS had a significantly higher incidence of MACE at 4 years (22.7% vs.
      13.7%, P = 0.03). CONCLUSIONS: Although the risk of MACE did not differ
      significantly within 4 years in this Korean population undergoing CAS and CEA,
      there was a higher risk of stroke with CAS during the periprocedural period.

PMID- 30092434
TI  - Predicting Factors Associated with Postoperative Hypotension following Carotid
      Artery Stenting.
AB  - BACKGROUND: Prolonged hemodynamic instability after carotid artery stenting (CAS)
      has been associated with increased incidence of stroke and other major adverse
      events. The objective of this study is to determine the factors associated with
      hypotension following CAS. In particular, this study evaluates whether
      involvement of the carotid bifurcation/bulb and degree of calcification can
      predict postoperative hypotension. METHODS: A retrospective review of 90 CASs
      performed in 88 patients at a single tertiary center was completed. In patients
      with proximal internal carotid stenosis involving the carotid bifurcation, the
      extent of bifurcation/bulb calcification on preoperative computed tomography
      angiography was assessed using a scoring system. Calcium scores were assigned
      based on the percent of circumferential calcification of carotid bifurcation as
      follows: grade 1, <10%; grade 2, 10-50%; grade 3, 50-90%; and grade 4, >90%.
      Perioperative factors associated with prolonged postoperative hypotension
      requiring vasopressor infusion were analyzed. RESULTS: Overall, postoperative
      hypotension requiring vasopressors occurred in 26 (28.9%) of CAS. There were no
      differences in baseline demographics, comorbidities, or CAS indication between
      patients who required postoperative vasopressors for hypotension and those who
      did not. The majority of patients (64.4%) were on 2 or more antihypertensive
      medications preoperatively. Stenosis involved carotid bifurcation in 64 (71.1%)
      cases. Of these, 27 (42.2%) were grade 1, 19 (29.7%) were grade 2, 10 (15.6%)
      were grade 3, and 8 (12.5%) were grade 4 based on our calcium scoring system. On
      risk-adjusted analysis, carotid bifurcation/bulb involvement (adjusted odds ratio
      [aOR] 4.5, 95% confidence interval [CI] 1.1-18.5) and preoperative regimen of 2
      or more antihypertensives (aOR 4.2, 95% CI 1.1-16.0) were independent predictors
      of hypotension requiring vasopressors following CAS. Among patients with carotid
      bifurcation involvement, severity of calcium score was not a significant
      predictor of postoperative hypotension. CONCLUSIONS: CAS for carotid stenosis
      involving the carotid bifurcation/bulb is associated with a higher risk for
      postoperative hypotension requiring vasopressors. Patients with preoperative
      hypertension requiring 2 or more antihypertensive medications are also at
      increased risk. However, severity of carotid bifurcation calcification is not a
      significant predictor of need for postoperative vasopressors.

PMID- 30092435
TI  - Long-term Outcomes after Transplant Renal Artery Stenosis Surgery.
AB  - The occurrence of transplant renal artery stenosis (TRAS) ranges from 1 to 23%
      and is associated with resistant hypertension, volume overload, graft
      dysfunction, and poor long-term graft and patient survival. Enhancing graft
      availability with expanded criteria donors results in the transplantation of
      kidneys with atherosclerotic arteries, increasing the risk of vascular
      complications. Although endovascular management is the first-line strategy in
      this context, in some patients, surgery has to be considered. We report the
      experience and long-term follow-up of TRAS surgery in a French kidney
      transplantation center. Between 2004 and 2009, 10 patients with postoperative
      TRAS, considered unfit for an endovascular procedure by a multidisciplinary team,
      were addressed for surgery. Mean time from transplantation to surgery was 139.8
      +/- 136.4 days. Clinical indications were oliguria, anuria, or acute decrease in
      urine output (n = 5), resistant hypertension (n = 4), and persistence of a
      decreased allograft function (n = 1). Imaging-revealed ostial stenosis is
      associated with external iliac artery stenosis (n = 3) or early bifurcation (n =
      2), and kinking (n = 5). Revascularization techniques consisted in a great
      saphenous vein bypass (n = 5) and internal iliac artery anastomosis (n = 5). In
      the postoperative period, there was no graft loss, but 2 patients required
      hemodialysis during the first week. Mean follow-up was 9.8 +/- 2.1 years. One
      patient lost his graft 10.3 years after transplantation due to chronic rejection,
      and 1 patient needed endovascular dilation. There was no graft loss at 5 years.
      Blood pressure was controlled in all patients. Surgical intervention for TRAS is
      safe and effective on graft survival and graft function and has to be considered
      for patients unsuitable for endovascular repair.

PMID- 30092436
TI  - Long-Term Outcomes of Percutaneous Stenting of Aortic Endograft Limb Occlusion.
AB  - INTRODUCTION: To investigate the safety and efficacy of percutaneous stenting for
      the management of chronic ischemia caused by endograft limb occlusion following
      endovascular aortic aneurysm repair (EVAR). METHODS: This is a retrospective,
      single-center study investigating all patients who underwent percutaneous
      endovascular covered or bare metal stent placement for the management of
      intermittent claudication (IC) or critical limb ischemia following EVAR limb
      occlusion, between January 2010 and October 2017. Cases suffering from acute limb
      ischemia were treated surgically and were excluded from the analysis. Primary
      outcome measures were technical success and symptoms-free interval. Secondary
      outcome measures included clinically driven target-lesion reintervention (TLR)
      free survival, primary patency, and complication rates. RESULTS: Of 29 limb
      occlusions, 11 limbs (11 patients; 100% male; mean age: 71.6 +/- 6.9 years) were
      treated percutaneously and were included in the study. The majority suffered from
      IC (10/11; 90.9%) with a single case of rest pain. Technical success was obtained
      in 10 patients (90%). No major complications occurred. Mean follow-up time was
      37.6 +/- 25.7 months. Stent grafts were mainly used, while and in 2 cases
      (18.18%), only nitinol bare stents were deployed. According to Kaplan-Meier
      analysis, both symptoms-free interval and primary patency were 83.33% in up to 5
      years follow-up. TLR-free survival was 100% at 5 years, as 2 cases of
      claudication relapse were managed conservatively. CONCLUSIONS: Percutaneous
      stenting for the management chronic ischemia due to EVAR limb occlusion is
      feasible and safe, with satisfactory long-term outcomes. Careful patient
      selection warrants clinical success.

PMID- 30092437
TI  - Successful Endovascular Treatment of a Ruptured Popliteal Artery Aneurysm in a
      Patient with Behcet Disease.
AB  - PURPOSE: Arterial involvement of Behcet disease is often found in the form of a
      rapidly expanding aneurysm. We report a case of successful treatment of a
      ruptured popliteal artery aneurysm with a stent-graft insertion. CASE REPORT: A
      55-year-old male patient was admitted because of pain and swelling in the right
      leg that had persisted for 15 days. Computed tomography (CT) angiography showed a
      contained rupture of a large right popliteal artery aneurysm. Laboratory tests
      showed elevated erythrocyte sedimentation rate (ESR) and C-reactive protein
      level. The patient had a history of recurrent oral and genital ulceration,
      folliculitis, and erythema nodosum. He was diagnosed as having Behcet disease
      with arterial involvement. After 5 days of immunosuppressant medications, the ESR
      decreased. A 7 mm * 10 cm stent graft was inserted into the right popliteal
      artery, and completion angiography showed the successfully excluded aneurysm. His
      symptoms were gradually relieved. The stent graft was patent on CT angiography 15
      months after the procedure. He has been followed up for 16 months with dual
      antiplatelet agents and immunosuppressive medications. CONCLUSIONS: Endovascular
      therapy for peripheral aneurysms in patients with Behcet disease is safe and
      minimally invasive. Careful follow-up to monitor disease progression is
      necessary.

PMID- 30092438
TI  - Extracranial Visceral Artery Aneurysms/Pseudoaneurysms Repaired with Flow
      Diverter Device Developed for Cerebral Aneurysms: Preliminary Results.
AB  - BACKGROUND: Recently, there has been a shift toward elective endovascular repair
      of visceral artery aneurysms (VAAs). Transcatheter embolization (TE) and covered
      stenting (CS) represent the 2 most used endovascular techniques; however, TE
      carries the potential risk of end-organ ischemia, while CS is challenging when
      the parent arteries are tortuous. Flow diverter devices (FDDs) developed for
      cerebral aneurysms maintain distal flow and are characterized by high
      navigability in tortuous arteries. This report describes our initial experience
      in using FDD developed for cerebral aneurysms to treat extracranial
      VAAs/pseudoaneurysm (VAP). METHODS: The study was conducted on patients affected
      by VAP, who underwent endovascular repair using FDD, between January 2015 and
      April 2017. All patients underwent preinterventional computed tomography
      angiography (CTA) for diagnosis and procedural planning. VAP features (type,
      location, size) and the diameter of both the proximal and distal parent arteries
      were recorded. Since TE or CS was contraindicated or failed in the previous
      attempt, VAPs were repaired through an elective endovascular procedure with FDD
      (Surpass; Stryker Neurovascular, Fremont, CA). Follow-up CTAs were performed
      within 6 months and at 24 months after the endovascular repair, evaluating
      patency and proper position of the FDD, the maximum diameter of the VAP, any
      perfusion of the sac, and adequacy of end-organ perfusion. RESULTS: Four VAPs
      were repaired by FDD in 4 patients (2 females; median age: 72 years, range: 64-80
      years). One patient suffered from cervical arterial anastomotic pseudoaneurysm,
      whereas the remaining VAPs were 2 splenic artery aneurysms and 1 common hepatic
      aneurysm. VAPs median size was 20 mm (range: 13-26 mm) with median parent artery
      caliber of 5 mm (range: 3-5 mm). The correct deployment of the device was
      obtained in all cases; 2/4 VAPs showed endoleak at the end of the procedure. At
      follow-up CTAs performed after the procedure in a median time of 25 months
      (range: 4-28 months), all devices were patent and not migrated. All VAPs showed
      shrinkage of the sac without endoleak or signs of end-organ ischemia.
      CONCLUSIONS: When high tortuosity and small caliber of the parent arteries
      prevent CS and the necessity to maintain vessel patency contraindicates TE, FDD
      could represent an option for the treatment of VAP; however, high costs and the
      off-label use in extracranial vessels demand an accurate selection of the
      patients suitable for the VAP treatment with FDD.

PMID- 30092439
TI  - Left Gastroepiploic Artery True Aneurysm: Case Report and Review of the
      Literature.
AB  - Although the aneurysm of the splenic artery represents the third most common
      abdominal arterial aneurysm next to the aortic and iliac aneurysms, the aneurysm
      of the gastroepiploic artery is extremely rare occurring at a frequency of 3-4%
      of all visceral arteries' aneurysms; only 17 cases have been reported in the
      English literature. We present the case of a 65-year-old woman with an
      asymptomatic visceral artery aneurysm, which was an incidental ultrasonography
      finding. Magnetic resonance imaging showed an arterial aneurysm close to the
      peripheral splenic artery with intense tortuosity of the celiac and splenic
      artery. Abdominal computed tomography angiography confirmed the existence of an
      arterial aneurysm with a diameter of 2.3 cm near the splenic hilus without
      identifying the involved vessel. Endoluminal treatment was considered cumbersome
      due to anticipated anatomic obstacles; the patient underwent an elective open
      surgery in which the tortuosity of the celiac and splenic arteries and the
      aneurysm of the left gastroepiploic artery were revealed. The aneurysm was
      resected after proximal and distal ligation of the gastroepiploic artery; the
      flow of the splenic artery was intact. Histologically, it was a true aneurysm.
      The patient left the hospital on the fourth postoperative day without any
      complication. Historically, most aneurysms of the gastroepiploic arteries have
      been observed in men in the sixth decade of their life and after rupture; in
      modern times, their early incidental apocalypse is frequent due to the widespread
      use of imaging studies. Diagnostic approach and preoperative planning is of
      paramount importance to avoid complications. Current therapeutic modalities
      include catheter-based techniques or laparoscopic surgery.

PMID- 30092440
TI  - Surgical Treatment of Symptomatic Aortic Aneurysm in a Patient with Anti
      neutrophil Cytoplasmic Antibody-associated Vasculitis: Case Report and Review of
      the Literature.
AB  - Vasculitis is an heterogeneous group of syndromes, which shares inflammation of
      blood vessel wall as the main feature. Anti-neutrophil cytoplasmic antibody
      (ANCA)-associated vasculitis (AAV) is a necrotizing vasculitis, with few or no
      immune deposits, predominantly affecting small vessels (i.e., capillaries,
      venules, arterioles, and small arteries), associated with ANCAs specific for
      myeloperoxidase or proteinase 3. Clinical manifestations may be heterogeneous but
      an involvement of lungs and kidneys frequently occurs. AAV of large vessels is a
      very rare condition whose standard therapy is medical approach. Surgical
      revascularization has been described in selected patients after medical failure
      or in emergent settings. We report the case of a patient affected by symptomatic
      infrarenal aortic aneurysm related to AAV, who underwent in-situ reconstruction
      by means of cryopreserved homograft.

PMID- 30092441
TI  - Internal Carotid Artery Tortuosity as a Rare Cause of Dysphagia: Case Report and
      Literature Review.
AB  - Abnormalities in the morphology of internal carotid artery are commonly
      identified but their natural history is not well known. Rarely, vascular
      abnormalities can cause mass effect causing dysphagia. We report the case of a
      patient presenting with long-standing dysphagia and choking during swallowing of
      solid food caused by an internal carotid artery tortuosity undergoing surgical
      treatment at our institution and we review the available literature.

PMID- 30092442
TI  - Ultrasound-Guided Direct Needle Engagement for Flush-Occluded Superficial Femoral
      Artery.
AB  - Flush ostial occlusion of the superficial femoral artery (SFA) is challenging for
      endovascular treatment. Neither ipsilateral nor contralateral access is easy. The
      drawback of ipsilateral common femoral artery (CFA) access is that the CFA is too
      short for catheter manipulation and sheath engagement. Contralateral retrograde
      CFA access could have merit, but it has the drawback of poor pushability and
      torquability in the manipulation of devices. The most challenging part of flush
      ostial occlusion is the difficulty of wire engagement into the SFA orifice. We
      describe a case of successful treatment of a flush-occluded long SFA lesion using
      ultrasound-guided direct ipsilateral ostial access.

PMID- 30092443
TI  - Drug-Coated versus Plain Balloon Angioplasty in Bypass Vein Grafts (the DRECOREST
      I-Study).
AB  - BACKGROUND: Stenosis is a known complication in bypass vein grafts for peripheral
      arterial disease. The aim of this study was to evaluate the effect of drug-coated
      balloons (DCBs) in the treatment of vein graft stenoses. DCBs may prevent
      restenosis in arterial lesions. One small prospective and larger retrospective
      and registry studies have failed to show benefit from DCBs in vein grafts.
      Prospective data are scarce. METHODS: Sixty patients treated for primary or
      recurrent stenosis in venous bypass grafts were randomized to DCB (n = 30) or
      standard balloon angioplasty (BA) (n = 30). Follow-up was 1 year. The primary
      outcome measure was target lesion revascularization (TLR). Secondary outcome
      measures were assisted primary patency and secondary patency and graft occlusion.
      RESULTS: Fifty-seven patients were analyzed. Three patients were excluded due to
      primary technical failure (2 DCB, 1 BA). Overall TLR rate was 34.5% and 46.4% in
      the DCB and BA groups, respectively (P = 0.33). Five (8.8%) grafts occluded
      during follow-up (1 DCB, 4 BA). Assisted primary patency was 93.1% (DCB) versus
      85.7% (BA) (P = 0.362) and secondary patency was 100% (DCB) versus 89.3% (BA) (P
      = 0.076). Subgroup analysis showed a significant benefit from DCB in the
      treatment of primary stenosis (TLR rate 15.0% vs. 18.9%, P = 0.03). CONCLUSION:
      There was no significant benefit from DCBs for treatment of vein graft stenosis
      compared to BA, although a trend in favor of DCBs could be seen. TRIAL
      REGISTRATION: ClinicalTrials.govNCT03023098.

PMID- 30092444
TI  - Comparison of the Cost of Drug-Eluting Stents versus Bare Metal Stents in the
      Treatment of Critical Limb Ischemia in the United States.
AB  - BACKGROUND: Despite significant technical advancement in the last decade, the
      durability of endovascular management of critical limb ischemia (CLI) remains
      highly debatable. Drug-eluting stents (DESs) are being popularized for the
      management of CLI after its precedent success in coronary intervention. Initial
      reports on the durability of DES are promising. However, little is known on the
      additional cost of this relatively newer technology. The aim of this study is to
      compare the cost of the traditional bare metal stents (BMSs) to the newly
      introduced DES in a large cohort of CLI patients. METHODS: Using the Premier
      database (2009-2015), we identified all patients with CLI undergoing DES and BMS.
      A multivariable generalized linear model was implemented to examine in-hospital
      cost adjusting for patients' characteristics, comorbidities, and regional
      characteristics. RESULTS: A total of 20,702 patients with CLI underwent
      peripheral artery revascularization using BMS (18,924 [91.41%]) or DES (1,778
      [8.6%]). Majority of patients were males (53%) and whites (71%). Patients
      undergoing BMS were slightly younger (median age [interquartile range]: 70 [62
      79] versus 71 [63-80]) and were more likely to be smokers (46% vs. 39%) and have
      a history of cerebrovascular disease (10% vs. 8%) and chronic pulmonary disease
      (24.5% vs. 20.9%) as compared with those undergoing DES (all P < 0.05). On the
      other hand, DES patients had a high prevalence of diabetes (4% vs. 3%) and renal
      disease (25% vs. 22%) (both P < 0.05). There was also a significant increase in
      the proportion of patients undergoing DES and a corresponding decrease in BMS (P
      < 0.001) over the study period. Median total in-hospitalization cost (BMS:
      $13,342 [8,574 to 21,166], DES: $13,243 [8,560-20,232], P = 0.76) was similar for
      both approaches. After adjusting for potential confounders, DES was associated
      with $407 higher cost than BMS (adjusted mean difference [95% confidence
      interval]: 407 [17 to 798], P = 0.04). In addition, the cost was $672 higher in
      teaching hospitals, $1,153 higher in Rural areas, and increased in all regions
      compared with the Midwest (adjusted mean difference [95% confidence interval]
      South: $293 [31 to 555], Northeast: $2,006 [1,517 to 2,495], West: $3,312 [2,930
      to 3,695], all P < 0.05). CONCLUSIONS: In this large cohort of CLI patients,
      after controlling for potential confounders, we demonstrated that the cost of
      endovascular revascularization is significantly higher in patients undergoing DES
      than those undergoing BMS. Regional disparities in cost were also observed.
      Further studies looking at the long-term durability and costs of DES versus BMS
      are needed.

PMID- 30092445
TI  - Early weight gain predicts later weight gain in depressed patients treated with
      antidepressants: Findings from the METADAP cohort.
AB  - BACKGROUND: Weight gain is a major side effect of antidepressant (AD) drugs. We
      assessed whether early weight gain is a predictor for long term weight gain in
      depressed patients treated with antidepressants. METHODS: In the six month
      prospective METADAP cohort, 260 non-overweight patients with a major depressive
      disorder (MDD), who have recently experienced a Major Depressive Episode (MDE)
      were assessed for early weight gain (>3%,>5%, and >7%) after one month of
      treatment, and for long term weight gain (>15% and >20%) after three and six
      months of treatment. ROC analysis was used to determine the predictive power of
      early weight gain. RESULTS: 12.4% (21/170) of patients became overweight after
      three months of treatment and 21.1% (26/123) were overweight after six months.
      Compared to non-early weight gainers, patients with early weight gain (>3%, >5%
      and >7%) were 11.3 (OR = 11.3, 95%CI: 4.6-27.6)], 9.9 (OR = 9.9, 95%CI: 3.6
      26.9)] and 17.8 (OR = 17.8, 95%CI: 6.4-49.4)] times, respectively, more at risk
      of late weight gain (>15%). ROC analysis showed that early weight gain (>3%)
      after one month of treatment, was the best predictor of long term weight gain
      (>=15%) after three months [Area Under the Curve (AUC )= 87%] and six months of
      treatment (AUC = 88%) PERSPECTIVES: Given that our baseline sample consisted of
      strictly non-overweight patients, the 3% threshold for weight gain after one
      month should be used as an indicator to initiate early weight monitoring in
      depressed patients treated with antidepressants. High attrition rate remains a
      limitation in this cohort and other cohorts in psychiatric settings. DISCLOSURES:
      Bruno Falissard consults for and received lecture fees from for E. Lilly, BMS,
      Servier, Sanofi-Aventis, GlaxoSmithKline, HRA, Roche, Boeringer Ingelheim, Bayer,
      Almirall, Allergan, Stallergene, Genzyme, Pierre Fabre, Astra Zeneca, Novartis,
      Janssen, Astellas, Biotronik, Daiichi-Sankyo, Gilead, MSD, Lundbeck. Florence
      Gressier received lecture fees from for Servier, Lundbeck and a grant from
      Servier. Mircea Polosan consults for and received lecture fees from Astra-Zeneca,
      Bristol Myers Squibb, Lundbeck, Otsuka and Servier. Emmanuel Haffen consults for
      and received lecture fees from Astra-Zeneca, Bristol Myers Squibb, Pfizer, Lilly,
      Lundbeck, Otsuka, Sanofi-Aventis, Servier. Philippe Chanson has received
      unrestricted research and educational grants from Ipsen, Novartis, Novo-Nordisk,
      and Pfizer for the Department of Endocrinology and Reproductive Diseases,
      Hopitaux Universitaires Paris-Sud and for INSERM U 693. He has served as
      investigator (principal or coordinator) for clinical trials funded by Novartis,
      Pfizer, Ipsen, Italopharmaco, Antisense, Prolor Biotech. He is member of Advisory
      Boards from Ipsen, Novartis, Viropharma. He gave lectures for Ipsen, Novartis,
      Pfizer, NovoNordisk. All the fees and honoraria were paid to his Institution.
      Bruno Falissard consults for and received lecture fees from NovoNordisk, MSD and
      Sanofi-Aventis. Laurent Bequemont has close family member working at Sanofi
      Aventis, consults for Sanofi-Aventis, Pfizer, Servier and received lecture fees
      from Genzyme, GlaxoSmithKline, Bristol-Myers Squibb and Merck Sharp and Dohme.
      Khalil El Asmar, Severine Trabado, Albane Vievard, Celine Verstuyft, Romain Colle
      and Emmanuelle Corruble have nothing to declare.

PMID- 30092446
TI  - An empirical evaluation of multivariate spatial crash frequency models.
AB  - Many studies have employed spatial, temporal, or a combination of both
      specifications for analysis of roadway crashes at different spatial levels.
      However, there is lack of a comprehensive study which compares the crash
      estimation performance of different spatial weight matrices and their combination
      with various temporal treatments. The current study fills the research gap by
      comparing different Full Bayesian (FB) multivariate spatiotemporal crash models.
      The pedestrian and bicyclist crash data across an eight-year period for 58
      counties in California were used as a case study. Three groups of models were
      developed based on temporal treatment, where each group comprised of 17 models
      differing on the basis of different adjacency- and distance-based spatial weight
      matrices. The first group of multivariate models incorporated only unstructured
      random error term and spatially structured conditional autoregressive (CAR) term.
      The second group built upon the former and introduced a linear time trend to
      develop a spatiotemporal model, while the third group allowed the interaction of
      space and time. The predictive performance of the alternate models across and
      within groups was assessed by employing several evaluation criteria. The modeling
      results demonstrated the robustness of models based on the similar signs and
      closeness of coefficients for the posterior estimates of parameters. For overall
      model comparison, the pure-distance model D0.5 demonstrated the best performance
      for different evaluation criteria based on training and test errors across three
      groups. The variability in performance of other distance models suggested that
      caution must be exercised for the choice of exponents. The correlation analysis
      revealed the presence of positive correlations among the criteria based on
      training errors, as well as with cross-validation. However, a very strong
      positive correlation was observed between the criteria based on effective number
      of parameters and posterior deviance, indicating that an increased number of
      parameters may not lead to improved model fit. This finding reinforced the
      importance of selecting the optimum weight matrix for spatial correlation as a
      more complex structure may not lead to expected advantages at model performance.
      For comparison among three groups of different temporal treatments, the third
      group demonstrated the best performance and conveyed the benefits of
      incorporating the spatial and temporal interaction. The results from ANOVA
      (analysis of variance) and HSD (Honest Significant Differences) tests also
      established the existence of statistical differences for the superiority of space
      time interactions models. However, the box and whisker plots demonstrated high
      variability among the models of the third group, suggesting that some models may
      not benefit from interaction term. For comparison among adjacency- and distance
      based models, the distance-based models were mostly observed to be superior.
      However, the greater variability of model performance associated with distance
      based models suggested for careful consideration during their selection.
      Additionally, it is important to note that the results observed in this study are
      specific to the county-level crash data of California. As such, the study does
      not recommend generalization of the results for extension to other spatial levels
      of roadway network, and readers and future research studies are advised to
      exercise caution before implementing the models.

PMID- 30092447
TI  - Withdrawal from functional Crassulacean acid metabolism (CAM) is accompanied by
      changes in both gene expression and activity of antioxidative enzymes.
AB  - In Mesembryanthemum crystallinum, crassulacean acid metabolism (CAM) is seemingly
      reversible, but unequivocal evidence for functional CAM withdrawal has yet to be
      shown. In this study, we confirmed the rapid downregulation of PEPC1 expression
      just 1 h after the removal of NaCl from the plant growth media. At the same time,
      the Delta malate values in desalted plants rapidly (1 d) re-established to values
      typical for C3 plants. This phenomenon allowed us to confirm functional CAM
      withdrawal in the desalted plants. Desalting altered the expression of the genes
      of the main antioxidative enzymes and/or the activity of their respective
      proteins; for catalase (CAT), both gene expression and protein activity were
      restored to levels observed in C3 plants in response to desalting, while for
      cooper-zinc superoxide dismutase (CuZnSOD) and ascorbate peroxidase (APX), only
      protein activity was restored. Therefore, we conclude that during the C3->CAM
      transition the CAM-specific antioxidative enzyme activity profile constitutes a
      transient and fully reversible response to abiotic stress.

PMID- 30092448
TI  - Communication impairment in Parkinson's disease: Impact of motor and cognitive
      symptoms on speech and language.
AB  - Communication impairment is common in Parkinson's disease (PD) and may have both
      motor speech control and cognitive-linguistic underpinnings. The neurobiology of
      communication impairment in PD is poorly understood, and work is needed to
      disentangle the relative contributions of motor and cognitive dysfunction. In
      clinical practice, cognitive-linguistic impairments are often overlooked despite
      the large body of research on this topic in neurocognitive and linguistics
      literature. In this review, we will discuss the roles of motor speech changes,
      cognitive and linguistic impairment, and other related functions in the
      communication disabilities of individuals with PD. We will describe the various
      types of communication difficulties in PD and tools for measuring these symptoms.
      We will discuss specific deficits that may further understanding of the
      neurobiology of communication impairment in PD, including voice and speech
      acoustic changes, linguistic processing and production difficulties, and pausing.
      We will emphasize the importance of an interdisciplinary approach and the patient
      perspective on daily communication in guiding future research.

PMID- 30092449
TI  - Synthesis, biological evaluation and molecular dynamics studies of 1,2,4-triazole
      clubbed Mannich bases.
AB  - The present work highlightsthe synthesis of a newer biologically active Mannich
      bases contributing 4-((4-fluorobenzylidene)amino)-5-(pyridin-4-yl)-4H-1,2,4
      triazole-3-thiol and various heterocyclic amines via N-Mannich reaction by the
      conventional method as well as microwave heating approach as a part of an
      environmentally benign synthetic protocol. All the synthesized compounds were
      characterized by spectral analysis and were screened for in vitro antimicrobial,
      antitubercular and antiprotozoal activity. The compound 4k was found to be most
      active respectively against S. aureus (MIC 12.5 MUM) and C. albicans (MIC 100
      MUM). The derivative 4 g displayed potency against L.mexicana and T. cruzi with
      IC50 value 1.01 and 3.33 MUM better than reference drug Miltefosina and
      Nifurtimox. The compound 4b displayed excellent potency against M. tuberculosis
      (MIC 6.25 MUM) in the primary screening. The computational studies revealed for
      that Mannich derivative (4b) showed a high affinity toward the active site of
      enzyme which provides a strong platform for new structure-based design efforts.
      The Lipinski's parameters showed good drug-likeness properties and can be
      developed as an oral drug candidate.

PMID- 30092450
TI  - Establishment of an induced pluripotent stem cell line from a retinitis
      pigmentosa patient with compound heterozygous CRB1 mutation.
AB  - The human iPSC line LEIi006-A was generated from dermal fibroblasts from a
      patient with retinitis pigmentosa using episomal plasmids containing OCT4, SOX2,
      KLF4, L-MYC, LIN28, mir302/367 microRNA and shRNA for p53. The iPSC cells carry
      compound heterozygous mutations (c.1892A > G and c.2548G > A) in the CRB1 gene.
      LEIi006-A expressed pluripotent stem cell markers, had a normal karyotype and
      could be differentiated into endoderm, mesoderm and ectodermal lineages, as well
      as retinal organoids.

PMID- 30092452
TI  - Use of high-resolution metabolomics for the identification of metabolic signals
      associated with traffic-related air pollution.
AB  - BACKGROUND: High-resolution metabolomics (HRM) is emerging as a sensitive tool
      for measuring environmental exposures and biological responses. The aim of this
      analysis is to assess the ability of high-resolution metabolomics (HRM) to
      reflect internal exposures to complex traffic-related air pollution mixtures.
      METHODS: We used untargeted HRM profiling to characterize plasma and saliva
      collected from participants in the Dorm Room Inhalation to Vehicle Emission
      (DRIVE) study to identify metabolic pathways associated with traffic emission
      exposures. We measured a suite of traffic-related pollutants at multiple ambient
      and indoor sites at varying distances from a major highway artery for 12 weeks in
      2014. In parallel, 54 students living in dormitories near (20 m) or far (1.4 km)
      from the highway contributed plasma and saliva samples. Untargeted HRM profiling
      was completed for both plasma and saliva samples; metabolite and metabolic
      pathway alternations were evaluated using a metabolome-wide association study
      (MWAS) framework with pathway analyses. RESULTS: Weekly levels of traffic
      pollutants were significantly higher at the near dorm when compared to the far
      dorm (p < 0.05 for all pollutants). In total, 20,766 metabolic features were
      extracted from plasma samples and 29,013 from saliva samples. 45% of features
      were detected and shared in both plasma and saliva samples. 1291 unique metabolic
      features were significantly associated with at least one or more traffic
      indicator, including black carbon, carbon monoxide, nitrogen oxides and fine
      particulate matter (p < 0.05 for all significant features), after controlling for
      confounding and false discovery rate. Pathway analysis of metabolic features
      associated with traffic exposure indicated elicitation of inflammatory and
      oxidative stress related pathways, including leukotriene and vitamin E
      metabolism. We confirmed the chemical identities of 10 metabolites associated
      with traffic pollutants, including arginine, histidine, gamma-linolenic acid, and
      hypoxanthine. CONCLUSIONS: Using HRM, we identified and verified biological
      perturbations associated with primary traffic pollutant in panel-based setting
      with repeated measurement. Observed response was consistent with endogenous
      metabolic signaling related to oxidative stress, inflammation, and nucleic acid
      damage and repair. Collectively, the current findings provide support for the use
      of untargeted HRM in the development of metabolic biomarkers of traffic pollution
      exposure and response.

PMID- 30092453
TI  - Exploring anxiety in schizophrenia: New light on a hidden figure.
AB  - Anxiety is among the least studied features of schizophrenia, despite evidence of
      its significant impact on disease outcome. This work aims to investigate the
      anxiety construct in a sample of outpatients with schizophrenia, exploring the
      interplay of clinical, neurocognitive and social cognitive domains, as well as
      adverse childhood experiences and their relative contribute in determining
      anxiety. A forward stepwise regression model was performed on a sample of 68
      outpatients with schizophrenia, to examine the predictive effect of different
      variables on anxiety. Predictors have been selected based on previous literature
      and include psychopathological, neurocognitive and social cognitive measures, as
      well as premorbid environmental factors. The analysis showed a significant
      contribution of childhood adverse experiences, followed by personal distress,
      while no significant effect was found for symptom's severity, nor global
      cognitive efficiency. The results show that anxiety is mainly determined by early
      environmental factors, as well as by socio-cognitive dimensions, such as personal
      distress. Data also suggest that anxiety can be considered as an independent
      construct, rather than as a mere epiphenomenon of the illness. The study has
      clinical implications as it highlights the importance of implementing both
      standardized assessments and group interventions specifically targeting anxiety
      in schizophrenia.

PMID- 30092454
TI  - Aerosol sources in subway environments.
AB  - Millions of people use rail subway public transport around the world, despite the
      relatively high particulate matter (PM) concentrations in these underground
      environments, requiring the identification and quantification of the aerosol
      source contributions to improve the air quality. An extensive aerosol monitoring
      campaign was carried out in eleven subway stations in the Barcelona metro system,
      belonging to seven subway lines. PM2.5 samples were collected during the metro
      operating hours and chemically analysed to determine major and trace elements,
      inorganic ions, and total carbon. The chemical compositions of subway components
      such as brake pads, rail tracks and pantographs were also determined. The mean
      PM2.5 concentrations varied widely among stations, ranging from 26 ug m-3 to 86
      ug m-3. Subway PM2.5 was mainly constituted by Fe2O3 (30-66%), followed by
      carbonaceous matter (18-37%) for the old stations, while for new stations
      equipped with Platform Screen Doors (PSD) these percentages go down to 21-44% and
      15-30%, respectively. Both the absolute concentrations and the relative abundance
      of key species differed for each subway station, although with common patterns
      within a given subway line. This is a result of the different emission chemical
      profiles in different subway lines (using diverse types of brakes and/or
      pantographs). The co-emission of different sources poses a problem for their
      separation by receptor models. Nevertheless, receptor modelling (Positive Matrix
      Factorization) was applied resulting in ten sources, five of them subway
      specific: RailWheel, RailWheel+Brake, Brake_A, Brake_B, Pb. The sum of their
      contributions accounted for 43-91% of bulk PM2.5 for the old stations and 21-52%
      for the stations with PSD. The decrease of the activity during the weekends
      resulted in a decrease (up to 56%) in the subway-specific sources contribution to
      the -already lower- bulk PM2.5 concentrations compared to weekdays. The health
      related elements are mainly apportioned (> 60%) by subway sources.

PMID- 30092451
TI  - Exposure to bisphenol A, chlorophenols, benzophenones, and parabens in relation
      to reproductive hormones in healthy women: A chemical mixture approach.
AB  - BACKGROUND: Little is known about the associations of bisphenol A, chlorophenols,
      benzophenones, and parabens with reproductive hormone levels in women. Our goal
      was to evaluate the associations between repeated measures of these chemicals and
      their mixtures with reproductive hormones in women. METHODS: Longitudinal urine
      samples from healthy, premenopausal women (n = 143 with 3-5 urine samples each)
      were measured for bisphenol A, five chlorophenols (2,4-dichlorophenol (2,4-DCP),
      2,5-dichlorophenol, 2,4,5-trichlorophenol, 2,4,6-trichlorophenol, triclosan), two
      ultraviolet (UV) filters (benzophenone-1, benzophenone-3), and eight parabens and
      their metabolites (benzyl, butyl, ethyl, heptyl, methyl, propyl, 4-hydroxybenzoic
      acid (4-HB), 3,4-dihydroxybenzoic acid (3,4-DHB)) over two menstrual cycles.
      Estradiol, progesterone, luteinizing hormone (LH), and follicle stimulating
      hormone (FSH) were measured in blood up to 8 times each menstrual cycle. Linear
      mixed models were used for both single and multi-chemical exposures estimated
      using principal component analysis. Four factors were identified including:
      paraben; paraben metabolites and BPA, phenols, and UV filters. Models were
      adjusted for creatinine, age, race, and body mass index and weighted with inverse
      probability of exposure weights to account for time varying confounding. RESULTS:
      In single-chemical models, 3,4-DHB was associated with estradiol (0.06 (95%
      confidence interval (CI): 0.001, 0.12)), 2-4-DCP with increased progesterone 0.14
      (0.06, 0.21) and decreased FSH -0.08 (-0.11, -0.04), and 4-HB was associated with
      increased FSH 0.07 (0.01, 0.13). In multi-chemical models, all factors were
      associated with increased progesterone (beta coefficient range: 0.15 for UV
      filter factor to 0.32 for paraben factor). The paraben factor and the paraben
      metabolite and BPA factor were associated with increased estradiol [0.21 (0.15,
      0.28); 0.12 (0.07, 0.18)]. The phenol and UV filter factors were associated with
      decreased estradiol, FSH, and LH. The UV filter factor showed the strongest
      inverse association with estradiol -0.16 (-0.22, -0.10), FSH -0.12 (-0.17, 
      0.07), and LH -0.17 (-0.23, -0.10). CONCLUSION: Mixtures of phenols were
      associated with changes in reproductive hormones. Such changes could contribute
      to adverse health in women but additional research is necessary.

PMID- 30092455
TI  - Ecological analysis of associations between groundwater quality and hypertension
      and cardiovascular disease in rural Saskatchewan, Canada using Bayesian
      hierarchical models and administrative health data.
AB  - Associations between groundwater quality and the prevalence of hypertension and
      ischemic heart disease were investigated in rural areas of the Canadian province
      of Saskatchewan. The partially ecological study was analyzed using Bayesian
      hierarchical models to account for spatial variability in risk. Exposure measures
      and health outcomes were estimated based on previously collected water quality
      surveillance data from public water supplies and private wells and administrative
      health data. Water quality exposures for each study region were estimated by
      applying geostatistical techniques to arsenic concentrations and principal
      component (PC) scores. The PC scores summarized groups of parameters measuring
      either health standards or aesthetic objectives described by the province.
      Generalized linear mixed models with a log link assessed associations between
      water quality and observed count of health outcomes relative to the expected
      value. The Bayesian models contained uncorrelated and spatially correlated random
      effects for each geographic region. Effect estimates were controlled for sex and
      age by stratification of case and expected case counts, for smoking by inclusion
      of sex- and age-specific prevalence of chronic obstructive pulmonary disease as a
      surrogate covariate, and for education and income by use of census data. There
      was no evidence for associations between groundwater arsenic concentrations in
      public or private water supplies and increased risk of hypertension or
      cardiovascular disease. An increase in the second aesthetic objectives PC score
      from public supplies was associated with a protective effect against ischemic
      heart disease. This PC value summarized hardness and magnesium Similarly, an
      increase in the second aesthetic objectives PC in private supplies was associated
      with decreased prevalence of hypertension. The results of this study are
      consistent with others demonstrating a relationship between elevated hardness and
      magnesium concentrations in drinking water and reduced risk of hypertension and
      cardiovascular disease. Further investigation is warranted with individual
      exposure history, particularly with respect to the potential beneficial effect of
      hard water on the prevalence of hypertension and cardiovascular disease.

PMID- 30092456
TI  - Effects of a multidisciplinary disease management programme with or without
      exercise training for heart failure patients: Secondary analysis of a randomized
      controlled trial.
AB  - BACKGROUND: Heart failure is a complex syndrome that causes substantial
      functional impairment and poor outcomes. Although multidisciplinary disease
      management programmes are effective, the role of additional outpatient-based
      exercise training and the effects of multidisciplinary disease management
      programmes for patients with contraindications to exercise training are unclear.
      OBJECTIVES: To compare the effects of the multidisciplinary disease management
      programme with and without exercise training on heart failure-related
      rehospitalization, disease knowledge, and functional capacity. DESIGN: Secondary
      analysis of a randomized controlled trial. PARTICIPANTS AND SETTING: Data for 212
      patients hospitalized for heart failure at a local teaching hospital in Taiwan
      were analysed. METHODS: Patients' data were assigned to three groups: control (n
      = 71), multidisciplinary disease management programme without exercise training
      (n = 70) or multidisciplinary disease management programme with exercise training
      (n = 71). The multidisciplinary disease management programme included
      comprehensive assessments, individualized education, optimizing medications, pre
      scheduled clinic visits, and encouraging regular physical activity at home.
      Outpatient-based exercise training was performed only in the multidisciplinary
      disease management programme with exercise training group. The control and the
      multidisciplinary disease management programme without exercise training groups
      were further divided into subgroups with and without contraindications to
      exercise training. Patients were followed up monthly for heart failure-related
      rehospitalizations for 1 year. Cox proportional hazard models and Kaplan-Meier
      analyses were used to identify the significant predictors of heart failure
      related rehospitalizations. A generalized estimation equation model was used to
      analyse the secondary outcomes, including disease knowledge and 6-min walking
      distance at baseline and 6 and 12 months after discharge. RESULTS: At 12 months
      after discharge, the multidisciplinary disease management programme with and
      without exercise training groups had significantly lower heart failure-related
      rehospitalization rates and better disease knowledge compared with the control
      group (p < 0.01). Only the multidisciplinary disease management programme with
      exercise training group had a significant improvement in 6-min walking distance
      (p < 0.05). For patients with contraindications to exercise, the
      multidisciplinary disease management programme significantly reduced heart
      failure-related rehospitalization rates at 12 months after discharge (p < 0.05).
      For those without contraindications, the event-lowering effect was only noted for
      the multidisciplinary disease management programme with exercise training group
      (p < 0.05). CONCLUSIONS: Outpatient-based exercise training is recommended to be
      incorporated into multidisciplinary disease management programmes for patients
      without exercise contraindications to improve disease outcomes and functional
      capacity. For patients with contraindications to exercise, a multidisciplinary
      disease management programme is recommended to improve patient outcomes.

PMID- 30092457
TI  - Electrochemiluminescence detection of human breast cancer cells using aptamer
      modified bipolar electrode mounted into  3D printed microchannel.
AB  - In the present manuscript, a closed bipolar electrode system integrated with
      electrochemiluminescence (ECL) detection has been introduced for sensitive
      diagnosis of human breast cancer cells (MCF-7). For sensitive and selective
      detection, the anodic pole of the bipolar electrode was modified with the AS1411
      aptamer, a specific aptamer for the nucleolin, and treated by the secondary
      aptamer modified gold nanoparticles. The electrochemiluminescence of luminol was
      followed in the presence of hydrogen peroxide on the anode pole of bipolar
      electrode (BPE) as an analytical signal. Moreover, 3D printed microchannels were
      used for the fabrication of BPE systems to minimize the required amounts of
      sample. The present aptasensor offers low cost, sensitive and selective cancer
      cell detection with two acceptable linear ranges. The first linear section
      appears within 10-100 cells and the latter is found to be within 100-700 cells.
      The limit of detection was about 10 cells.

PMID- 30092458
TI  - Uniform sensing layer of immiscible enzyme-mediator compounds developed via a
      spray aerosol mixing technique towards low cost minimally invasive microneedle
      continuous glucose monitoring devices.
AB  - In this study, a uniformly mixed sensing layer of typically immiscible compounds,
      such as tetrathiafulvalene (TTF) mediator and glucose oxidase (GOx) enzyme, was
      developed using a simultaneous spray deposition technique ideal for mass
      production of glucose sensors at low cost while exhibiting enhanced amperometric
      response. For comparison, the sensors were fabricated via three different
      methods: conventional drop-cast of TTF and GOx compounds in subsequent layers
      (DL), spray deposition of the compounds in subsequent layers (SL), and spray
      mixing of the compounds as one uniform layer (SM). Uniformity of the sensing
      layers was investigated via Scanning Electron Microscopy (SEM) and Energy
      Dispersive X-Ray Spectroscopy (EDX) techniques demonstrating an even distribution
      of the TTF and GOx throughout the sensing layer for the SM sensors. The
      amperometric studies showed a significantly larger maximum current response, Imax
      and sensitivity for the SM sensors as compared to the SL and DL sensors. The
      significantly better performance of the SM sensors correlated well with the even
      distribution of TTF and GOx throughout the sensing layer, resulting in enhanced
      electron transfer and redox reaction between GOx and TTF. The SM spray technique
      was then applied to deposit a uniformly mixed sensing layer on to 3D microneedle
      arrays to provide minimally invasive continuous glucose monitoring (CGM). In-vivo
      studies showed amperometric response from the microneedle CGM device was
      compatible to changes in blood glucose levels measured via the standard finger
      prick tests. Importantly, the deposition technique is suitable for mass
      production of the microneedle CGM at very low cost.

PMID- 30092459
TI  - Quality of critical care clinical practice guidelines: Assessment with AGREE II
      instrument.
AB  - STUDY OBJECTIVE: Clinical practice guidelines (CPGs) are cornerstones for the
      management of critically ill patients. Numerous CPGs have been generated in
      critical care medicine, but their qualities have never been systematically
      appraised. The aim of the present study was to systematically assess the quality
      of critical care CPGs. DESIGN: A systematic electronic search was performed in
      PubMed and Scopus. All critical care CPGs were included for analysis. SETTING:
      Not applicable. PATIENTS: Not applicable. INTERVENTION: None. MEASUREMENTS: The
      Appraisal of guidelines for research & evaluation II (AGREE II) instrument was
      employed to appraise the quality. CPGs were assessed independently by three
      raters and intraclass correlation coefficient to represent the agreement among
      raters. MAIN RESULTS: A total of 89 CPGs were included for quantitative analysis.
      The results showed that domain 1 (scope and purpose) had the highest scores
      (0.93, IQR: 0.89-0.98) and domain 2 (stakeholder involvement) had the lowest
      scores (0.37, IQR: 0.30-0.46). The overall score was 0.83 (IQR: 0.67-0.83).
      Publication year was not associated with scaled scores in each domain. Domain 2
      (stakeholder involvement) was significantly associated with the number of
      societies (coefficient: 0.702, p = 0.033). Also, greater number of societies were
      associated with higher scaled scores of domain 3 (coefficient: 0.768, p = 0.027),
      4 (coefficient: 0.730, p = 0.029) and 5 (coefficient: 0.995, p = 0.023).
      CONCLUSIONS: The study showed that the reporting quality of critical care CPGs
      were suboptimal. The reporting quality varied across the six domains, with the
      highest quality in domain 1 and lowest quality in domain 2. Strenuous efforts
      need to be made to improve the reporting of critical care CPGs.

PMID- 30092460
TI  - Event segmentation: Cross-linguistic differences in verbal and non-verbal tasks.
AB  - Events, as fundamental units in human perception and cognition, are limited by
      quality changes of objects over time. In the present study, we investigate the
      role of language in shaping event units. Given fundamental cross-linguistic
      differences in the concepts encoded in the verb, as in French compared to German,
      event unit formation was tested for motion events in a verbal (online event
      description, experiment 1), as well as a non-verbal task (Newtson-test,
      experiment 2). In German, motion and direction are described by a single
      assertion, i.e. one verb encoding manner (to walk ...), in conjunction with
      adpositional phrases for path and direction (... over x across y toward z). In
      contrast, when information on path and direction is encoded in the verb, as
      typically in French, each path segment requires a separate assertion (head for x,
      cross y, approach z). Both experiments were based on short naturalistic video
      clips showing a figure moving through space along a path either without changing
      orientation/direction (control), or with changes in orientation/direction
      (critical). Analysis of the verbal task concerned the probability of producing
      more than one assertion to refer to the motion events presented in the clips; in
      the non-verbal event segmentation task, the analysis concerned the probability of
      marking an event boundary, as indicated by pressing a button. Results show that
      in French, the probability of producing more than one assertion was significantly
      higher in the critical condition (experiment 1) and the probability to identify
      an event boundary was also significantly higher (experiment 2), compared to the
      German participants but only in the critical condition. The findings indicate
      language-driven effects in event unit formation. The results are discussed in the
      context of theories of event cognition, thereby focusing on the role of language
      in the formation of cognitive structures.

PMID- 30092461
TI  - Mnemonic accessibility affects statement believability: The effect of listening
      to others selectively practicing beliefs.
AB  - Belief endorsement is rarely a fully deliberative process. Oftentimes, one's
      beliefs are influenced by superficial characteristics of the belief evaluation
      experience. Here, we show that by manipulating the mnemonic accessibility of
      particular beliefs we can alter their believability. We use a well-established
      socio-cognitive paradigm (i.e., the social version of the selective practice
      paradigm) to increase the mnemonic accessibility of some beliefs and induce
      forgetting in others. We find that listening to a speaker selectively practicing
      beliefs results in changes in believability. Beliefs that are mentioned become
      mnemonically accessible and exhibit an increase in believability, while beliefs
      that are related to those mentioned exrience mnemonic suppression, which results
      in decreased believability. Importantly, the latter effect occurs regardless of
      whether the belief is scientifically accurate or inaccurate. Furthermore, beliefs
      that are endorsed with moderate-strength are particularly susceptible to
      mnemonically-induced believability changes. These findings, we argue, have the
      potential to guide interventions aimed at correcting misinformation in vulnerable
      communities.

PMID- 30092462
TI  - Microvascular Decompression for Oculomotor Nerve Palsy Due to Compression by
      Infundibular Dilatation of Posterior Communicating Artery.
AB  - BACKGROUND: Oculomotor nerve palsy is occasionally a key indicator of an internal
      carotid posterior communicating (ICPC) artery bifurcation aneurysm. The interval
      between the onset of palsy and the time of surgery is considered to be the most
      important factor affecting recovery from oculomotor nerve palsy. We encountered a
      rare case of oculomotor nerve palsy due to compression by the infundibular
      dilatation of the posterior communicating artery (PcomA) rather than by an ICPC
      aneurysm. CASE DESCRIPTION: We report the case of a 70-year-old woman who
      presented with pain in the left forehead and left oculomotor nerve palsy with a
      prominence at the bifurcation of the left internal carotid artery and PcomA on
      neuroradiologic imaging, indicating a small aneurysm. However, the positional
      relationship between the bulging lesion and PcomA was not apparent. The
      intraoperative microscopic view showed that the lesion was an infundibular
      dilatation of the PcomA rather than an aneurysm, compressing the oculomotor
      nerve. Microvascular decompression of the lesion resulted in the disappearance of
      her symptoms after 3 months. CONCLUSIONS: For the treatment of a symptomatic ICPC
      unruptured aneurysm, direct observation by open surgery is important when the
      relationship between the PcomA and aneurysm is not clear by neuroradiologic
      imaging.

PMID- 30092463
TI  - Biomechanical Fixation Properties of the Cortical Bone Trajectory in the
      Osteoporotic Lumbar Spine.
AB  - OBJECTIVE: Selecting optimal strategies for improving fixation in osteoporotic
      lumbar spine is an important issue in clinical research. Cortical bone trajectory
      (CBT) screws have been proven to enhance screw pullout strength, but
      biomechanical efficacy of these screws remains understudied. The aim of this
      study was to evaluate biomechanical efficacy of CBT screws in osteoporotic lumbar
      spine. METHODS: Thirty-one vertebrae from 14 cadaveric lumbar spines were
      obtained. All specimens were measured by computed tomography; the diameter of
      pedicles, excluding those of vertebral bodies with very small pedicle
      developments, was calculated. After measuring bone mineral density, the CBT screw
      was randomly inserted into 1 side, and the traditional trajectory (TT) screw was
      inserted into the contralateral side. Maximum insertional torque was recorded
      after screw insertion. Of vertebrae, 21 were subjected to pullout testing at a
      rate of 5 mm/minute, and 10 were subjected to cyclic fatigue testing. Each
      construct was loaded until exceeding 5 mm. RESULTS: Average bone mineral density
      was 0.567 +/- 0.101 g/cm2. CBT screws had higher maximum insertional torque
      (degrees of freedom = 30, t = 5.78, P < 0.001, 0.333 N-m vs. 0.188 N-m) and
      higher axial pullout strength (degrees of freedom = 20, t = 7.41, P < 0.001, 394
      N vs. 241 N) than TT screws. Increased bone mineral density was not significantly
      associated with higher pullout load. Compared with TT screws, CBT screws showed
      better resistance to fatigue testing and required more cycles to exceed 5 mm
      (degrees of freedom = 9, t = 5.62, P < 0.001, 6161 cycles vs. 3639 cycles).
      Failure load for displacing screws was also significantly greater for CBT screws
      than for TT screws (degrees of freedom = 9, t = 5.75, P < 0.001, 443 N vs. 317
      N). CONCLUSIONS: CBT screws had better biomechanical fixation in osteoporotic
      lumbar spine compared with standard pedicle screws.

PMID- 30092464
TI  - Predicting the Occurrence of Hemorrhagic Cerebral Hyperperfusion Syndrome Using
      Regional Cerebral Blood Flow After Direct Bypass Surgery in Patients with
      Moyamoya Disease.
AB  - OBJECTIVE: Superficial temporal artery-middle cerebral artery anastomosis is an
      established treatment for moyamoya disease. However, hemorrhagic cerebral
      hyperperfusion syndrome (CHS) leads to poor outcomes. This study aimed to
      identify predictors of hemorrhagic CHS based on regional cerebral blood flow
      (rCBF) in patients with moyamoya disease. METHODS: The study included 251
      hemispheres in 155 patients with moyamoya disease who underwent preoperative and
      postoperative rCBF measurements and superficial temporal artery-middle cerebral
      artery double anastomosis. We used rCBF increase rate for predicting hemorrhagic
      CHS. rCBF increase rate was calculated by 2 methods. In method 1, the rCBF value
      on the operated side was compared with the rCBF value on the nonoperated side. In
      method 2, the postoperative rCBF value on the operated side was compared with the
      preoperative rCBF value on the operated side. Patients were classified into 4
      groups according to rCBF increase rate to predict risk of hemorrhagic CHS.
      RESULTS: Hemorrhagic CHS occurred in 7 (2.8%) hemispheres (no children). Severe
      hemorrhagic CHS occurred in only 1 (0.4%) hemisphere. Hemorrhagic CHS was
      observed in patients with >=30% rCBF increase according to method 1 and >=50%
      rCBF increase according to method 2 and was most frequently noted in >=100% rCBF
      increase. CONCLUSIONS: Predictors for hemorrhagic CHS were >=30% rCBF increase
      when using method 1 and >=50% increase when using method 2.

PMID- 30092465
TI  - Cervical Intervertebral Disc Degeneration Contributes to Dizziness: A Clinical
      and Immunohistochemical Study.
AB  - OBJECTIVES: Dizziness often happens in patients with chronic neck pain with only
      cervical disc degeneration but without cervical radiculopathy or myelopathy. We
      prospectively selected a series of patients who showed cervical disc degeneration
      with concomitant chronic neck pain and intractable dizziness who did not respond
      to conservative treatment to test a new diagnostic method for this dizziness, to
      analyze the results of anterior cervical discectomy and fusion (ACDF) surgery
      based on the test, and to explore its pathogenesis. METHODS: Seventy-seven
      patients who had a transient neck pain and dizziness relief after injection of
      bupivacaine into a suspected disc were included in the study. In total, 52
      underwent ACDF as surgery group, and 25 refused surgery and accepted conservative
      treatments as conservative group from June, 2015 to October, 2016 with subsequent
      follow-up to 1 year. The outcomes were visual analogue scale for neck pain, Neck
      Disability Index, and intensity and frequency of dizziness. During ACDF, the 72
      specimens of degenerative cervical discs were collected to determine the
      innervation in degenerative cervical discs immunohistochemically. RESULTS: After
      surgery, the patients experienced a significant reduction in neck pain and
      dizziness. Symptomatic relief in surgery group was obviously better than
      conservative group at each time point of follow-up (P = 0.001). Ruffini
      corpuscles and substance P-positive free nerve fibers were obviously increased in
      the number and deeply ingrown into the inner degenerative cervical discs.
      CONCLUSIONS: Current clinical and immunohistochemical studies strongly suggest
      that chronic neck pain and intractable dizziness in this series of patients stem
      from the degenerative cervical discs.

PMID- 30092466
TI  - Applicability, Safety, and Cost-Effectiveness of Improvised External Ventricular
      Drainage: An Observational Study of Tunisian Neurosurgery Inpatients.
AB  - OBJECTIVE: External ventricular drainage (EVD) is an emergent neurosurgical
      procedure. Many commercial sets are available for EVD that are not always
      obtainable in all hospitals. The aim of our study was to describe new techniques
      to perform EVD using simple improvised materials to check the real-world
      applicability of the same device in the management of acute hydrocephalus and its
      effectiveness and safety. METHODS: We illustrated 2 techniques for a "do it
      yourself" improvised EVD device using materials available even in non
      neurosurgery-dedicated operating rooms. We performed an observational study in
      our institution (April 2015 to December 2016). We included all patients
      presenting with acute hydrocephalus and requiring EVD. RESULTS: During a 20-month
      period, the new EVD device was used as a lifesaving solution for 33 patients.
      Good outcomes were noted in 11 of the 33 patients (33%). The EVD was complicated
      by fatal meningitis in 4 of the patients (12%). Malfunction occurred in 6
      patients. The new EVD device costs less than US$20 for the first technique and
      less than US$10 for the second technique. In contrast, the cost of a standard EVD
      set ranges from US$170 to US$380 in Tunisia. CONCLUSIONS: The new EVD device has
      the potential to improve the quality of efficiency of care in difficult economic
      times that have changed the medical landscape, because it is both easy to make
      and cost-effective. Because it is an inexpensive technique, it could also be
      suitable for low-income countries, where neurosurgery is not yet the first and
      foremost health priority.

PMID- 30092467
TI  - Retrosigmoid Transtentorial Approach: Technical Nuances and Quantification of
      Benefit From Tentorial Incision.
AB  - OBJECTIVE: The transtentorial extension of the retrosigmoid approach allows for
      improved visualization of the brainstem and petroclival region. This approach is
      an important tool in the skull base surgeon's armamentarium for pathologies
      involving the petroclival region. It has been shown that the addition of
      tentorial transection improves the exposed surface area of the brainstem.
      However, no data have been reported regarding the depth of the additional
      anterior and medial exposure. The goal of the present study was to describe the
      additional depth of exposure gained by performing tentorial transection. This
      information allows surgeons to preoperatively estimate the amount of operative
      exposure gained by this technique. METHODS: Five preserved cadaveric heads were
      dissected using frameless image guidance. A standard retrosigmoid craniotomy was
      performed, followed by tentorial transection. The boundaries of the surgical
      exposure and depth of the surgical field were compared before and after tentorial
      transection. RESULTS: After transection, we found a 20.1-mm increase in anterior
      exposure (P < 0.01) and a 13-mm increase in medial exposure (P < 0.01). No
      significant difference was found in the extent of the superior (P = 0.32) or
      lateral (P = 0.07) exposure. The surgical working distance increased
      significantly from 68.8 to 90.3 mm (P < 0.01). CONCLUSIONS: When performing
      retrosigmoid craniotomy, the addition of tentorial transection allows for a
      significant increase in anterior and medial exposure with no significant increase
      in superior or lateral exposure.

PMID- 30092468
TI  - Intelligent Surgeon's Arm Supporting System iArmS in Microscopic Neurosurgery
      Utilizing Robotic Technology.
AB  - BACKGROUND: Based on our previous reports, stabilizing the surgeon's arm with an
      intraoperative armrest is linked to improved precision of microsurgical and
      endoscopic procedures. We developed the robotic intelligent surgeon's arm
      supporting system iArmS, which automatically follows the surgeon's arm and fixes
      it at an adequate position. METHODS: iArmS has 3 states-free, hold, and wait
      which can be carefully chosen automatically as follows: In free state, the
      armholder follows the surgeon's arm. In hold state, iArmS supports the surgeon's
      arm weight by fixing the armholder. In wait state, the surgeon can move his or
      her arm away from the armholder. Also, the surgeon can change the armrest
      position while looking through the microscope and can continue the microsurgical
      procedure while holding surgical instruments. From February 2015 to January 2017,
      iArmS was used in 108 microsurgeries at 3 of the authors' institutions by 14
      board-certified neurosurgeons, including the authors. After using iArmS, to
      quantify neurosurgeons' satisfaction, a scaling evaluation guide based on visual
      analog scales was designed to be completed by contributing neurosurgeons,
      including authors. RESULTS: iArmS decreased fatigue and reduced hand trembles
      experienced by surgeons. Continuous accurate motions of microinstruments were
      performed without any difficulties. There were no complications related to use of
      iArmS. CONCLUSIONS: iArmS allows continuous precise manipulations that provide
      high-quality surgical results in neurosurgical techniques. Moreover, iArmS is a
      useful automatic tool for holding and following the surgeon's arm.

PMID- 30092469
TI  - Combined Endoscopic Endonasal and Video-microscopic Transcranial Approach with
      Preoperative Embolization for a Posterior Pituitary Tumor.
AB  - BACKGROUND: Posterior pituitary tumor is rare, and its optimal surgical strategy
      is undetermined. Surgical removal of posterior pituitary tumors is often
      complicated by their hypervascularity. Prevention and preparation for excessive
      hemorrhage is crucial for safe resection. CASE DESCRIPTION: A 69-year-old woman
      presented with bitemporal hemianopsia and was found to have a sellar tumor with
      suprasellar extension, resembling a pituitary adenoma. Microscopic
      transsphenoidal resection was attempted but was interrupted by a massive
      intraoperative hemorrhage. Pathologic diagnosis was a spindle cell oncocytoma,
      and she was referred to our institution. She underwent preoperative embolization
      to decrease tumor vascularity, and resection was performed using a combined
      endoscopic endonasal and video-microscopic transcranial approach, using a 4K
      three-dimensional (3D) video microscope. The final diagnosis was a posterior
      pituitary tumor with immunopositivity for thyroid transcription factor-1, with
      preferred interpretation as a pituicytoma. CONCLUSIONS: A combined endonasal and
      transcranial approach with preoperative embolization is a useful strategy for
      hypervascular posterior pituitary tumors. A 4K 3D video microscope is compact,
      and it provides high-resolution images, contributing larger surgical space and
      facilitating a multi-team surgery.

PMID- 30092470
TI  - Transforaminal Endoscopic Excision of Intradural Lumbar Disk Herniation and Dural
      Repair.
AB  - BACKGROUND: Intradural disk herniation is a rare entity with <0.3%-1% of all disk
      herniations and at an L2-L3 level even rarer. The dural defects repairs on
      ventral aspect are technically challenging and may not be possible after
      durotomy, so many authors have placed fascia, muscle, or plugging by the
      hemostatic material. The surgical treatment of intradural disk herniation is
      usually posterior open surgery with formal durotomy to remove the disk fragments
      with good to fair results. Poorer outcome occurs in late-presenting cases. CASE
      REPORT: We report on a 78-year-old man who presented with spontaneous low back
      pain and bilateral buttock pain aggravated for 1 month with severe walking
      difficulty without bowel and bladder symptoms. Magnetic resonance imaging
      revealed disk herniation at the L2-L3 level. He underwent a transforaminal
      endoscopic removal of intradural disk fragments via the original rent in the
      anterolateral aspect of the dura, and sealing was performed with dural patch and
      Gelfoam without any lumbar drain. The patient's symptom significantly improved
      postoperatively with muscle power improved to grade 5 on day 1 with no
      cerebrospinal fluid leakage, and he was mobilized with a lumbar orthosis on the
      first postoperative day. Postoperative and at 6-month follow-up, magnetic
      resonance imaging revealed adequate decompression and successful sealing of the
      ventral dural defect. CONCLUSIONS: To our knowledge, this is the first case of
      transforaminal endoscopic treatment of intradural disk herniation at an L2-L3
      level in which good clinical outcomes were obtained and maintained until recent
      follow-up of 8 months.

PMID- 30092471
TI  - Hyperglycemia Is Associated with Island Sign in Patients with Intracerebral
      Hemorrhage.
AB  - OBJECTIVES: The prognostic value of admission serum glucose for early hematoma
      growth in patients with intracranial hemorrhage remains controversial. Island
      sign is a novel imaging predictor for early hematoma growth, implying multifocal
      active bleeding. The aim of this study is to investigate the potential
      associations between hyperglycemia and early hematoma expansion in patients with
      intracranial hemorrhage with or without island sign. PATIENTS AND METHODS:
      Clinical characteristics and radiologic parameters were retrospectively obtained
      from the electronic medical record. Admission blood glucose was measured within
      24 hours from disease onset. Hematoma expansion and island sign were estimated by
      2 experienced reviewers from initial and follow-up computed tomography scans.
      Multivariate logistic regression analyses were used to explore the associations
      of hematoma expansion and island sign on other clinical variables. RESULTS: In
      total, 187 patients were enrolled in current study; 61 patients were presented to
      have early hematoma expansion, whereas 32 exhibited island sign. The average
      blood glucose level was 7.64 mmol/L among all patients. The multivariate logistic
      regression analyses revealed that the time from ictus to initial computed
      tomography scan, Glasgow Coma Scale score on admission, hematoma volume, island
      sign, and hyperglycemia were associated with hematoma expansion, whereas only
      admission serum glucose and hematoma size were associated with island sign.
      CONCLUSIONS: Admission serum glucose is associated with hematoma growth and
      prevalence of island sign, respectively. These results indicated that elevated
      blood glucose level plays a pathological role in active bleeding. Further studies
      concerning exact molecular signal pathway are urgently required.

PMID- 30092472
TI  - Giant Dumbbell-Shaped Thoracic Schwannoma in an Elderly Patient Resected Through
      a Single-Stage Combined Laminectomy and Video-Assisted Thoracoscopy: Surgical
      Strategy and Technical Nuances.
AB  - BACKGROUND: Dumbbell-shaped schwannomas involving the spinal canal, the
      intervertebral foramen, and the thoracic cavity are rare lesions. Surgical
      treatment represents a challenge, and there is no consensus regarding ideal
      management. Two major surgical routes have been used: combined laminectomy and
      open thoracotomy or posterolateral extrapleural approach with wide bone removal.
      This report describes a relatively easy surgical strategy, combined laminectomy
      and thoracoscopy, which allows safe resection under an adequate view with low
      risk of spinal instability, pain, or respiratory problems. CASE DESCRIPTION: A 74
      year-old man presented with rapidly progressing motor impairment caused by a
      dumbbell-shaped, 65-mm, Eden type III lesion at the T5 level. Magnetic resonance
      imaging showed an intraspinal-extradural mass extending into the chest cavity and
      causing severe spinal cord compression. The patient underwent single-stage
      surgery performed by a neurosurgical and thoracic team. The extradural and
      foraminal tumor components were first removed through a 1-level laminectomy with
      foraminotomy and without facetectomy. Subsequently, video-assisted thoracic
      surgery was performed to approach the anterior paraspinal component. Total tumor
      removal, confirmed with postoperative magnetic resonance imaging, was achieved.
      Pathologic diagnosis was schwannoma. The postoperative course was uneventful. The
      patient's neurologic deficits resolved, and he experienced minimal pain after the
      operation. CONCLUSIONS: A single-stage operation using combined laminectomy and
      video-assisted thoracic surgery is a safe and efficacious strategy for achieving
      total removal of dumbbell-shaped thoracic schwannomas, even in cases involving
      giant lesions and elderly patients.

PMID- 30092473
TI  - Titanium Mesh Implant Exposure Due To Pressure Gradient Fluctuation.
AB  - OBJECTIVE: Titanium mesh implants (TMIs) are used for various purposes in
      craniotomy. Although delayed implant exposure and thinning of the overlying skin
      are well-known complications, the mechanism has not yet been elucidated. We
      reviewed our cases and propose a mechanism for TMI exposure. METHODS: From 2009
      to 2018, we treated 14 patients with delayed titanium implant exposure after
      craniotomy. The exposed titanium implant was a TMI in 4 patients, a titanium mesh
      plate in 6 patients, and a titanium fixation plate with holes in 4 patients. We
      reviewed the preoperative computed tomography (CT) scans and operative findings.
      RESULTS: The interval between craniotomy and implant exposure was 13 years
      (range, 5-27). Implant exposure occurred at the temporal region in 7 patients,
      frontal region in 6 patients, and parietal region in 1 patient. The skin ulcer
      size ranged from 0.25 to 10 cm2 (mean, 1.95). In the patients with TMI exposure,
      the dura was expanded, and no residual epidural space was identified on the CT
      scans; however, epidural dead space was revealed on the CT scan in the patients
      with titanium mesh plate or titanium fixation plate exposure. CONCLUSIONS: We
      believe that the key factor resulting in delayed titanium mesh exposure is the
      pressure gradient between the atmosphere and the intracranial space. Fluctuation
      of this gradient exerts dynamic stress on the tissue in the mesh holes and the
      adjacent tissue, resulting in tissue damage and implant exposure.

PMID- 30092475
TI  - Rupture of Giant Anterior Sacral Meningocele in a Patient with Marfan Syndrome:
      Diagnosis and Management.
AB  - BACKGROUND: Marfan syndrome is a genetic disorder that results in the weakening
      of connective tissues. Dural ectasia has been defined as a feature of Marfan
      syndrome and is present in up to 92% of patients. Rarely, dural ectasia can erode
      through the sacrum expanding into an anterior sacral meningocele. CASE
      DESCRIPTION: Information for this case report was gathered from patient notes and
      imaging from the patient chart. This is a case of a 46-year-old woman who
      presented with urinary incontinence, early satiety, and back pain in the setting
      of a known anterior sacral meningocele. Before operative management, the anterior
      sacral meningocele ruptured with the patient presenting signs and symptoms of
      intracranial hypotension. Conservative management did not alleviate the pain. She
      was ultimately managed with posterior sacroplasty followed by anterior sacral
      meningocele resection and placement of a lumboperitoneal shunt. The patient did
      not have reaccumulation of the meningocele or recurrent symptoms at the latest
      follow-up. CONCLUSIONS: The progression of dural ectasia in Marfan syndrome to an
      anterior sacral meningocele is uncommon. It is important to identify the
      characteristics associated with an expanding dural ectasia as this patient's
      symptoms progressed over time and the meningocele grew large. Given its rarity,
      there are no guidelines in place regarding size at which repair of an anterior
      sacral meningocele should occur prophylactically. It is important to review these
      cases in order continue to learn about progression, management, and outcomes of
      patients with an anterior sacral meningocele.

PMID- 30092476
TI  - Transblepharo-Preseptal Modified Orbitozygomatic Craniotomy for Treatment of
      Ruptured Aneurysm: 3-Dimensional Operative Video.
AB  - Various supraorbital approaches to the anterior cranial fossa using a
      transciliary or supraciliary incision have been described. An orbitotomy is a
      valuable addition to the standard supraorbital keyhole approach offering an
      extended angle of exposure with minimal frontal lobe retraction. The
      transpalpebral approach is common in oculoplastic surgery and offers excellent
      cosmetic outcomes using the natural crease of the superior eyelid. This approach
      avoids risk of eyebrow alopecia and damage to the frontalis muscle or frontalis
      branches of the facial nerve. A transblepharo-preseptal or transpalpebral
      modified orbitozygomatic approach for the treatment of unruptured anterior
      circulation aneurysms has been reported. Our experience with this approach has
      been that it has potential to offer anterior skull base access and outcomes that
      are not inferior to traditional approaches for selected cases including ruptured
      anterior circulation aneurysms. Moreover, we believe this approach can provide
      excellent cosmetic results and could minimize surgical time and hospitalization
      stay. This 3-dimensional video presents the case of a 47-year-old female with
      sudden-onset headache and seizure (Video 1). She was found to have a subarachnoid
      hemorrhage resulting from rupture of a carotid terminus aneurysm. Considering the
      location and morphology of the aneurysm, as well as the patient's eyelid anatomy,
      clip ligation via a transblepharo-preseptal modified orbitozygomatic craniotomy
      was recommended. Aneurysm clipping was uneventful, and postoperative imaging
      showed complete occlusion. The patient was discharged neurologically intact.

PMID- 30092474
TI  - Resting-State Functional Magnetic Resonance Imaging Connectivity of the Brain Is
      Associated with Altered Sensorimotor Function in Patients with Cervical
      Spondylosis.
AB  - OBJECTIVE: To determine the relationship between functional connectivity (FC)
      using resting-state functional magnetic resonance imaging (MRI) and neurological
      impairment in patients with cervical spondylosis and healthy controls. METHODS: A
      total of 24 patients with cervical spondylosis with or without myelopathy and 17
      neurologically intact, healthy volunteer subjects were prospectively enrolled in
      a cross-sectional study involving observational MRI and evaluation of
      neurological function using the modified Japanese Orthopedic Association (mJOA)
      score. Seed-to-seed connectivity and seed-to-voxel connectivity on functional MRI
      data were performed using a general linear model of connectivity with respect to
      age and mJOA score. RESULTS: Increased FC was observed with increasing
      neurological impairment in patients with cervical stenosis within sensorimotor
      areas, including precentral gyrus, postcentral gyrus, and supplemental motor
      regions, using both seed-to-seed and seed-to-voxel analyses. The anterior
      cingulate showed increasing connectivity with the supplemental motor area,
      thalamus, and cerebellum with increasing neurological function. Similarly, the
      thalamus, cerebellum, and putamen presented with increasing connectivity to both
      the bilateral precuneus and the posterior cingulate with an increasing mJOA
      score. CONCLUSIONS: Patients with cervical spondylosis exhibiting neurological
      impairment experience changes in brain connectivity similar to that of patients
      with chronic traumatic spinal cord injury. These results suggest an increase in
      FC within sensorimotor regions with increasing neurological impairment and
      decreased connectivity between the cerebellum, putamen, and thalamus to the
      anterior and posterior cingulate and frontal lobe regions.

PMID- 30092477
TI  - A Modified Percutaneous Endoscopic Technique to Remove Extraforaminal Disk
      Herniation at the L5-S1 Segment.
AB  - OBJECTIVE: To introduce a modified percutaneous endoscopic lumbar diskectomy
      (PELD) technique to remove extraforaminal disk herniation at the L5-S1 segment,
      including the technical essentials and preliminary results. METHODS: The
      geometric parameters of the transverse process, facet joint, and sacrum (TFS)
      space based on imaging examination were measured in 100 common patients. The
      technical essentials, including working cannula placement and disk removal
      involved in the technique, were described. Ten cases (7 men and 3 women) with
      extraforaminal disk herniation at L5-S1 were surgically treated with the PELD
      technique through the TFS space from June 2015 to March 2017. RESULTS: The
      maximum diameter of the TFS space varied from 2.73 to 11.81 mm (6.84 +/- 2.01 mm)
      on the left and 3.00 to 10.47 mm (7.02 +/- 2.05 mm) on the right. The distance of
      possible skin entry points from midline varied from 33.28 to 84.18 mm, and the
      distance of external iliac vessels to skin varied from 70.05 to 119.14 mm. All 10
      patients who underwent the modified PELD technique were back to previous
      activities in 1 month. Visual analog scale (VAS) or Oswestry Disability Index
      (ODI) scores reduced to 2.5 +/- 2.0 or 25.4 +/- 10.8 from 7.5 +/- 1.3 or 75.2 +/-
      13.3, respectively, 1 day after operation. At 30 days after the operation, the
      VAS score was 1.0 +/- 0.6 and ODI score was 10.2 +/- 3.2. No neurologic deficit
      or surgical site infection occurred. CONCLUSIONS: We introduced a modified PELD
      technique to remove extraforaminal disk herniation at the L5-S1 segment. This
      technique was less invasive, effective, and safe. We also summarized a detailed
      protocol to identify and remove the herniated disk for nerve protection.

PMID- 30092478
TI  - Intracranial venous hypertension in craniosynostosis: mechanistic underpinnings
      and therapeutic implications.
AB  - Patients with complex, multisutural, and syndromic craniosynostosis frequently
      exhibit intracranial hypertension. The intracranial hypertension cannot be
      entirely attributed to craniocephalic disproportion with calvarial restriction as
      cranial vault expansion does not consistently alleviate elevated intracranial
      pressure. Evidence most strongly supports a multifactorial interaction, including
      venous hypertension along with other pathogenic processes. Patients with
      craniosynostosis exhibit marked venous anomalies, including stenosis of the
      jugular/sigmoid complex and transverse sinuses, as well as extensive transosseous
      venous collaterals. These abnormal intracranial-extracranial occipital venous
      collaterals may represent anomalous development, with persistence and subsequent
      enlargement of channels normally present in the fetus, either as a primary defect
      or as non-regression in response to failure of development of the jugular/sigmoid
      complexes. It has been suggested by some authors that venous hypertension in
      patients with craniosynostosis may be treated directly via jugular
      foraminoplasty, venous stenting, or jugular venous bypass, though these options
      are not in common clinical practice. Obstructive sleep apnea, occurring as a
      consequence of midface hypoplasia, may also contribute to intracranial
      hypertension in syndromic craniosynostosis patients. Thus, correction of facial
      deformities, as well as posterior fossa decompression, may also play important
      roles in treatment of intracranial hypertension. Determining the precise
      mechanistic underpinnings underlying intracranial hypertension in any given
      patient with craniosynostosis requires individualized workup and management.

PMID- 30092479
TI  - Preoperative Hematologic Inflammatory Markers as Prognostic Factors in Patients
      with Glioma.
AB  - OBJECTIVE: Hematologic inflammatory markers are simple, inexpensive prognostic
      markers for various conditions. The prognostic significance of the neutrophil-to
      lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to
      lymphocyte ratio (MLR), and red blood cell distribution width (RDW) has been
      shown in a variety of tumors. We evaluated the prognostic value of these markers
      in glioma. METHODS: We performed a retrospective medical record review of 219
      patients with glioma from January 2012 to January 2017, evaluating the effect of
      NLR, PLR, MLR, and RDW on prognosis. Correlations among these hematologic
      inflammatory markers were also examined. RESULTS: The patients were divided into
      high and low groups using the cutoff points from the receiver operating
      characteristic curves. High NLR was associated with a higher tumor grade (P =
      0.000). Kaplan-Meier survival analyses showed that the high NLR, PLR, and MLR
      groups experienced inferior median overall survival (OS) compared with the low
      NLR, PLR, and MLR groups (11 vs. 32 months; P = 0.000; 12 vs. 21 months; P =
      0.001; and 12 vs. 22 months; P = 0.006, respectively). No significant difference
      was found in the median OS between the high and low RDW groups (15 vs. 23 months;
      P = 0.184). Multivariate analysis demonstrated that NLR was an independent
      predictor of OS (hazard ratio, 1.758; P = 0.008). CONCLUSIONS: A high
      preoperative NLR, PLR, and MLR was predictive of a poor prognosis for patients
      with glioma. NLR was an independent prognostic factor for OS in patients with
      glioma.

PMID- 30092480
TI  - Myelocystocele Mimicking Myelomeningocele: A Case Report and Review of the
      Literature.
AB  - BACKGROUND: Myelocystoceles, which are classified as closed neural tube defects,
      are usually covered by skin and rarely complicated by hydrocephalus. We
      encountered an unusual case of a terminal myelocystocele with hydrocephalus with
      clinical characteristics of a myelomeningocele. CASE DESCRIPTION: Severe
      hydrocephalus and a lumbosacral lesion were detected in the fetus of a gravid 34
      year-old woman. Cesarean section was performed at 37 weeks. The neonate presented
      with a lumbosacral mass with a partial skin defect. As myelomeningocele was
      suspected, the neonate underwent surgery on the day of birth. The intraoperative
      findings pointed to a myelocystocele rather than a myelomeningocele. After
      insertion of a ventriculoperitoneal shunt, the neonate was discharged without any
      neurologic deficits. CONCLUSIONS: Presence of skin abnormalities, hydrocephalus,
      and lumbosacral mass strongly suggests a diagnosis of myelomeningocele. However,
      such cases should be differentiated from myelocystocele, especially when
      associated with severe hydrocephalus.

PMID- 30092481
TI  - Computed Tomographic Black Hole Sign Predicts Postoperative Rehemorrhage in
      Patients with Spontaneous Intracranial Hemorrhage Following Stereotactic
      Minimally Invasive Surgery.
AB  - OBJECTIVES: Determining the value of the computed tomographic black hole sign in
      predicting postoperative rehemorrhage in patients with intracranial hemorrhage
      (ICH) underwent minimally invasive surgery (MIS). METHODS: Two hundred ninety
      five patients with spontaneous ICH underwent stereotactic MIS within 24 hours
      after admission. Ninety-eight patients (33%) demonstrated a black hole sign on
      initial computed tomography (CT). Postoperative rehemorrhage occurred in 68
      patients (named the rehemorrhage group, including patients with and without black
      hole sign) and the other 227 patients (non-rehemorrhage group) did not show
      rehemorrhage. Multivariable logistic regression analyses were performed to assess
      the values of the black hole sign. RESULTS: Postoperative rehemorrhage occurred
      in 57 of the 98 (58.2%) patients with the black hole sign, and in 11 of the 197
      (5.58%) patients without the black hole sign. In the rehemorrhage group, 39
      patients (57.4%) were found to have the black hole sign. However, only 59
      patients (25.99%) from the non-rehemorrhage group showed the black hole sign. The
      sensitivity, specificity, and positive and negative predictive values of the
      black hole sign for predicting postoperative rehemorrhage were 57.4%, 74%, 39.8%,
      and 85.3%, respectively. The odd ratio for the black hole sign, the hematoma
      irregularity, and the CT value for predicting the postoperative rehemorrhage were
      10.501, 9.631, and 4.750, respectively. CONCLUSIONS: The black hole sign on
      initial CT could predict the postoperative rehemorrhage following the minimally
      invasive procedures.

PMID- 30092482
TI  - Microsurgical Treatment of Unruptured Anterior Choroidal Artery Aneurysms:
      Incidence of and Risk Factors for Procedure-Related Complications.
AB  - OBJECTIVE: To describe our experiences with microsurgical treatment of unruptured
      anterior choroidal artery (AchA) aneurysms, and to evaluate the incidence of and
      risk factors for procedure-related complications. METHODS: The study included 110
      patients treated between January 2012 and December 2016. All patients met the
      following criteria: 1) microsurgical treatment of an unruptured AchA aneurysm was
      performed; and 2) clinical and radiographic follow-up data were available,
      including findings from preoperative digital subtraction angiography. The
      incidence of and risk factors for procedure-related complications were
      retrospectively evaluated. The chi2 test and Mann-Whitney U test were used in
      statistical analysis, and univariate analysis and multivariate logistic
      regression analysis were conducted. RESULTS: Procedure-related complications
      occurred in 5 patients (4.5%), including symptomatic complications in 4 patients
      (3.6%) and asymptomatic complications in 1 patient (0.9%). Multivariate logistic
      regression analysis indicated that the angle between the vertical line to the
      cranial base and the axis of the communicating segment of the internal carotid
      artery (MiC angle) (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.13
      5.26; P = 0.038) and the angle between the projection line of the aneurysmal dome
      and the axis of the communicating segment of the internal carotid artery (DC
      angle) (OR, 3.82; 95% CI, 1.49-11.7; P = 0.014) were independent risk factors for
      procedure-related complications. CONCLUSIONS: When microsurgical treatment of
      unruptured AchA aneurysms was performed, the procedure-related complication rate
      was 4.5%. Patients with AchA aneurysms with a smaller MiC angle and smaller DC
      angle may be at a higher risk of procedure-related complications when undergoing
      microsurgical treatment.

PMID- 30092483
TI  - Establishment of stable microalgal-bacterial consortium in liquid digestate for
      nutrient removal and biomass accumulation.
AB  - In this study, a microalgal-bacterial consortium (MBC) was established in liquid
      digestate (LD) by optimizing sequencing batch reactor (SBR) operating parameters
      and microalgae inoculation to address the abovementioned challenges. The bacteria
      from LD SBR-Activated Sludge System effluent under the optimum conditions of 25 
      degrees C, 7.0 g/L MLSS, 5 mg/L DO concentration, and 6 h hydraulic retention
      time with 0.5 mg/L DW Chlorella sp. BWY-1 could form stable MBCs outdoors in an
      airlift photoreactor. The stable MBC facilitates the continuous removal of
      nitrogen and phosphorus, promotes the accumulation of biomass and lipids, and
      contributes to the improvement of the sedimentation. The results from this study
      provided a new technique for the purification and utilization of LD, more
      importantly decreasing the environmental threat caused by improperly processed
      LD.

PMID- 30092484
TI  - Production optimization and characterization of mannooligosaccharide generating
      beta-mannanase from Aspergillus oryzae.
AB  - A multi-tolerant beta-mannanase (ManAo) was produced by Aspergillus oryzae on
      copra meal, a low-cost agro waste. Under statistically optimized conditions, 4.3
      fold increase in beta-mannanase production (434 U/gds) was obtained. Purified
      ManAo had MW ~34 kDa and specific activity of 335.85 U/mg with optimum activity
      at 60  degrees C and at pH 5.0. Activity of ManAo was enhanced by most metal ions
      and modulators while maximum enhancement was noticed with Ag+ and Triton X-100.
      Km and Vmax were 2.7 mg/mL and 1388.8 umol/min/mg for locust bean gum while the
      enzyme showed lower affinity towards konjac gum (8.8 mg/mL, 555.5 umol/min/mg).
      Evaluation of various thermodynamic parameters indicated high-efficiency of the
      ManAo with activation energy 12.42 KJ/mol and 23.31 KJ/mol towards LBG and konjac
      gum, respectively. End product analysis of beta-mannanase action by fluorescence
      assisted carbohydrate electrophoresis (FACE) revealed the generation of sugars
      from DP 1-4 with some higher DP MOS from different mannans.

PMID- 30092485
TI  - One-pot co-catalysis of corncob with dilute hydrochloric acid and tin-based solid
      acid for the enhancement of furfural production.
AB  - A newly synthesized solid acid catalyst SO42-/SnO2-diatomite was prepared for
      synthesizing furfural from corncob in the presence of homogeneous Bronsted acid.
      The relationship between pKa of Bronsted acid and turnover frequency (TOF) of co
      catalysis with Bronsted acid plus SO42-/SnO2-diatomite was explored on the
      conversion of corncob to furfural. HCl (pKa = -7.0) (0.5 wt%) plus SO42-/SnO2
      diatomite (3.6 wt%) gave the highest furfural yield (40.1%) with TOF value at
      2.98 h-1 in the aqueous media. In the gamma-valerolactone-water (6:4, v:v)
      biphasic media containing 15 g/L ZnCl2, one-pot conversion of corncob with co
      catalysts gave a furfural yield of 68.9% at 170  degrees C for 30 min.
      Additionally, an efficient SO42-/SnO2-diatomite recycling was achieved with a
      productivity of 15.6 g furfural/(g solid acid.day) after 5 cycles of repeated
      use. Clearly, this one-pot co-catalysis process has high potential application
      for furfural production in future.

PMID- 30092486
TI  - Influence of inherent hierarchical porous char with alkali and alkaline earth
      metallic species on lignin pyrolysis.
AB  - This study aimed to explore the influence of inherent hierarchical porous char
      with alkali and alkaline earth metallic species (AAEMs) during pyrolysis of
      lignin derived from agricultural crop residues in a laboratory fixed-bed at 550 
      degrees C. A catalytic strategy was implemented to investigate volatile-char
      interactions based on ex situ lignin pyrolysis. The physico-chemical properties
      of the AAEMs-loaded char were characterized by FTIR, XRD, SEM-EDX and N2 nitrogen
      adsorption analyses. Results indicated that AAEMs-loaded char had a large
      specific surface area, hierarchical porosity, amorphous carbon structure, surface
      active functional groups and highly dispersed metal species. Specifically, the
      specific surface area of AAEMs-loaded char was significantly reduced owing to
      coke deposition after interaction with pyrolysis vapours. Bio-oil composition
      revealed substantial increases in phenol, o-cresol, p-cresol and catechol. These
      increases were mainly attributed to demethylation, demethoxylation, or alkyl
      substitution reaction. The experimental results confirmed the occurrence of
      significant volatile-char interactions during lignin pyrolysis.

PMID- 30092487
TI  - Production of d-xylonic acid using a non-recombinant Corynebacterium glutamicum
      strain.
AB  - It was found that Corynebacterium glutamicum DeltaiolR devoid of the
      transcriptional regulator IolR accumulates high amounts of d-xylonate when
      cultivated in the presence of d-xylose. Detailed analyses of constructed deletion
      mutants revealed that the putative myo-inositol 2-dehydrogenase IolG also acts as
      d-xylose dehydrogenase and is mainly responsible for d-xylonate oxidation in this
      organism. Process development for d-xylonate production was initiated by
      cultivating C. glutamicum DeltaiolR on defined d-xylose/d-glucose mixtures under
      batch and fed-batch conditions. The resulting yield matched the theoretical
      maximum of 1 mol mol-1 and high volumetric productivities of up to 4 g L-1 h-1
      could be achieved. Subsequently, a novel one-pot sequential hydrolysis and
      fermentation process based on optimized medium containing hydrolyzed sugarcane
      bagasse was developed. Cost-efficiency and abundance of second-generation
      substrates, good performance indicators, and enhanced market access using a non
      recombinant strain open the perspective for a commercially viable bioprocess for
      d-xylonate production in the near future.

PMID- 30092488
TI  - Leptin-regulated autophagy plays a role in long-term neurobehavioral injury after
      neonatal seizures and the regulation of zinc/cPLA2 and CaMK II signaling in
      cerebral cortex.
AB  - Metabolic disorders play an important role in the pathogenesis of many
      neurological diseases. Recent evidence suggests that leptin levels in peripheral
      blood and brain are lower in patients with epilepsy. Leptin is an energy
      regulating hormone that plays a neuroprotective role in neurodegenerative
      diseases and brain trauma. However, little is known about the effects and
      molecular mechanisms of leptin treatment on long-term neurobehavioral impairment
      caused by developmental seizures. The present study evaluated whether chronic
      leptin treatment protected against neurobehavioral impairments induced by
      recurrent seizures in newborns treated with flurothyl. We also examined the
      effect of leptin on the expression of zinc/cPLA2-related autophagy signaling
      molecules and CaMKII in the cerebral cortex. Twenty Sprague-Dawley rats (6 days
      after birth, P6) were randomly divided into two groups, a neonatal seizure group
      and control group. Rats were subdivided on P13 into control, control + leptin
      (leptin, 2 mg/kg/day, continuous 10 days), seizure (RS), and seizure + leptin
      group (RS + leptin, 2 mg/kg/day for 10 consecutive days). Neurological behavioral
      parameters (negative geotaxis reaction reflex, righting reflex, cliff avoidance
      reflex, forelimb suspension reflex and open field test) were observed from P23 to
      P30. mRNA and protein levels in the cerebral cortex were detected using real-time
      RT-PCR and Western blotting, respectively. Flurothyl-induced seizures (RS group)
      produced long-term abnormal neurobehavior, which was improved with leptin
      treatment. Chronic leptin treatment restored several expression parameters
      affected by neonatal seizures, including seizure-induced up-regulated zinc
      transporter ZnT1/ZIP7, lipid membrane injury-related cPLA2, autophagy marker
      beclin-1/bcl2, LC3II/LC3I, and its execution molecule cathepsin-E, and down
      regulated memory marker CaMK II alpha. Our results suggest that the early use of
      leptin after neonatal recurrent seizures may exert neuroprotective effects and
      antagonize the long-term neurobehavioral impairment caused by seizures. Autophagy
      mediated Zn/cPLA2 and CaMK II signaling in the cerebral cortex may be involved in
      the neuroprotective effect of leptin. Our results provide new clues for anti
      epileptogenetic treatment.

PMID- 30092489
TI  - Perampanel chronic treatment does not induce tolerance and decreases tolerance to
      clobazam in genetically epilepsy prone rats.
AB  - Tolerance to some therapeutic effects of antiepileptic drugs may account for the
      development of pharmacoresistance in patients with epilepsy. In the present
      study, following oral acute pretreatment with the new antiepileptic drug
      perampanel (0.1, 0.3, 1 or 3 mg/kg), we observed that the drug significantly and
      dose-dependently attenuated the seizure phases (clonus and tonus) of audiogenic
      seizures in genetically epilepsy prone rats (GEPR-9 s), a genetic model of reflex
      generalized epilepsy. In addition, the GEPR-9 s were administered orally with
      perampanel (1 or 3 mg/kg) once daily for 10 weeks in order to study the possible
      development of tolerance, and when animals were subjected to auditory stimulation
      we observed that the ED50 values against clonus or tonus were not significantly
      different from those observed after single administration. Furthermore, the
      duration of anticonvulsant effects observed between 60 min and 9 h following oral
      administration of perampanel (1 mg/kg) were similar in acute and after chronic
      treatment. In another group of experiments, clobazam (0.75, 1.5, 3, 6, 9, 12 and
      15 mg/kg) after acute administration was able to dose-dependently reduce the
      severity of the audiogenic seizures in GEPR-9 s. When clobazam (6 or 12 mg/kg)
      was administered alone for 10 consecutive weeks a clear development of tolerance
      to its anticonvulsant effects within approximately seven weeks was observed. In
      addition, we observed that when clobazam (6 mg/kg) was co-administered with
      perampanel (1 mg/kg), the latter drug was able to attenuate the development of
      tolerance to the antiseizure activity of clobazam. The present data indicate that
      both perampanel and clobazam are effective against audiogenic seizures, however,
      clobazam effects are hampered by the development of tolerance. Furthermore,
      concomitant treatment with perampanel slows development of tolerance to the
      anticonvulsant effects of clobazam in GEPR-9 s.

PMID- 30092490
TI  - The project vita: A dynamic knowledge management tool.
AB  - A project vita is a comprehensive index of factual information about a project's
      activities and achievements. Like an individual's professional curriculum vita or
      resume, it serves as evidence of past performance and capacity for future
      endeavors. This article situates the project vita as a knowledge management tool
      for use by large-scale research and development projects or coalitions. In such
      complex endeavors, the variety and scope of the knowledge generated can quickly
      outpace project staff attempts to collect, classify, disseminate, and support the
      effective use of the constant stream of information being produced. We describe
      how to develop a project vita and utilize it to support several essential project
      functions, including communication, evaluation, management, and as a portal to
      products.

PMID- 30092491
TI  - Is culturally based prevention effective? Results from a 3-year tribal substance
      use prevention program.
AB  - American Indian youth substance use is a major public health concern. To date,
      there has been limited evaluation of American Indian youth substance use
      prevention programs. Evaluation of prevention programs is necessary to understand
      the aspects of programming that are effective or not effective. This mixed
      methods evaluation focuses on select outcomes of a 3-year culturally-based
      prevention program located in six American Indian communities in the Rocky
      Mountain Region. The goals of the prevention program are to reduce binge drinking
      by 30% and increase community readiness by 1-point over a 5- year period. In the
      first year of the program, community members worked with program staff to develop
      an evaluation plan that would measure the following outcomes: lowering substance
      use, increasing community readiness, and increasing the reach of prevention
      messaging through culturally based prevention. The primary research questions
      this outcome evaluation sought to answer were as follows: 1) Are there
      differences in American Indian youth who participate in culturally-based
      prevention activities compared with American Indian youth who do not participate
      in these activities? 2) Was the prevention program effective in increasing
      community readiness over a 3-year period? 3) Did community involvement in
      prevention activities increase overtime? Results from this evaluation indicate
      that substance use was similar among intervention (n = 200) and non-intervention
      youth (n = 369). This was somewhat surprising because Intervention youth reported
      higher levels of social support and community connections than non-intervention
      group youth. Community readiness decreased -.81 point from 2015 to 2017. The
      reach of prevention activities increased 365% from 2015 to 2017. We provide
      lessons learned that may help other communities as they document outcomes related
      to prevention efforts. Substance use is a multi-faceted problem facing our
      communities, families, schools, and nation. Innovative, effective, culturally
      based prevention programs like the one highlighted in this paper underscore the
      need for primary prevention strategies.

PMID- 30092492
TI  - Infrared spectroscopic and computational studies on formamide solutions of Ca2+.
      Vibrational frequencies of formamide and modes of coordination to Ca2.
AB  - Infrared spectroscopy for formamide (FA) solutions of Ca(ClO4)2 shows that both
      CN stretch (nuCN) and CO stretch (nuCO) bands of FA undergo upshifts in the
      presence of Ca2+. Modeling of Ca2+ in FA solutions is accomplished by quantum
      chemical calculations for Ca2+(FA)n (n = 1-8) complexes with Polarizable
      Continuum Model (PCM). The calculations indicate that bidentate Ca2+(FA)4
      complexes are not consistent with the observed upshift of the nuCN band, although
      a bidentate coordination of four FA molecules via both O and N atoms was assumed
      in a previous study of the same system. The experimental results are reasonably
      reproduced by adopting Ca2+(FA)7 and Ca2+(FA)8 complexes with a monodentate
      coordination of all FA molecules via the O atom. A strong coupling among the CO
      oscillators is shown to be responsible for the upshifts of the nuCO modes despite
      the O atom coordination.

PMID- 30092493
TI  - Two-photon isomerization triggers two-photon-excited fluorescence of an
      azobenzene derivative.
AB  - Photoisomerization provides a general means for photo-controlling molecular
      structure and function, and two-photon induced isomerization has some advantages
      over one-photon processes. Here, we report the two-photon absorption (TPA)
      induced optical properties and characteristics of an azobenzene derivative,
      namely N-(3,4,5-octanoxyphenyl)-N'-4-[(4-hydroxyphenyl)azophenyl]1,3,4-oxadiazole
      (AOB-t8). With the activation of red light, the photoproduct of cis-AOB-t8
      isomers has been unambiguously identified, and the two-photon induced
      isomerization process of AOB-t8 in THF is characterized with the relevant rate
      constants of forward and backward reactions. The TPA coefficients and cross
      sections of AOB-t8 at different wavelengths, and nonlinear optical refractive
      index are determined from femtosecond nonlinear optical measurements.
      Particularly, the results indicate that the two-photon excited emission can be
      effectively triggered by the two-photon-induced isomerization from trans- to cis
      AOB-t8, demonstrating an on-switch from non-fluorescence to visible blue
      emission. Consistent with the observations from one-photon excitation, we suggest
      that the enhanced two-photon excited fluorescence of AOB-t8 solution originates
      from the combined contribution of cis-AOB-t8 monomer and its aggregates, i.e.,
      the conformation transition from trans- to cis-AOB-t8 opens the emission channel
      and the self-assembly aggregation of cis-AOB-t8 isomers further enhances the
      fluorescence upon red light excitation.

PMID- 30092494
TI  - Heterogeneity of calcium clock functions in dormant, dysrhythmically and
      rhythmically firing single pacemaker cells isolated from SA node.
AB  - Current understanding of how cardiac pacemaker cells operate is based mainly on
      studies in isolated single sinoatrial node cells (SANC), specifically those that
      rhythmically fire action potentials similar to the in vivo behavior of the intact
      sinoatrial node. However, only a small fraction of SANC exhibit rhythmic firing
      after isolation. Other SANC behaviors have not been studied. Here, for the first
      time, we studied all single cells isolated from the sinoatrial node of the guinea
      pig, including traditionally studied rhythmically firing cells ('rhythmic SANC'),
      dysrhythmically firing cells ('dysrhythmic SANC') and cells without any apparent
      spontaneous firing activity ('dormant SANC'). Action potential-induced cytosolic
      Ca2+ transients and spontaneous local Ca2+ releases (LCRs) were measured with a
      2D camera. LCRs were present not only in rhythmically firing SANC, but also in
      dormant and dysrhythmic SANC. While rhythmic SANC were characterized by large
      LCRs synchronized in space and time towards late diastole, dysrhythmic and
      dormant SANC exhibited smaller LCRs that appeared stochastically and were widely
      distributed in time. beta-adrenergic receptor (betaAR) stimulation increased LCR
      size and synchronized LCR occurrences in all dysrhythmic and a third of dormant
      cells (25 of 75 cells tested). In response to betaAR stimulation, these dormant
      SANC developed automaticity, and LCRs became coupled to spontaneous action
      potential-induced cytosolic Ca2+ transients. Conversely, dormant SANC that did
      not develop automaticity showed no significant change in average LCR
      characteristics. The majority of dysrhythmic cells became rhythmic in response to
      betaAR stimulation, with the rate of action potential-induced cytosolic Ca2+
      transients substantially increasing. In summary, isolated SANC can be broadly
      categorized into three major populations: dormant, dysrhythmic, and rhythmic. We
      interpret our results based on simulations of a numerical model of SANC operating
      as a coupled-clock system. On this basis, the two previously unstudied
      dysrhythmic and dormant cell populations have intrinsically partially or
      completely uncoupled clocks. Such cells can be recruited to fire rhythmically in
      response to betaAR stimulation via increased rhythmic LCR activity and
      ameliorated coupling between the Ca2+ and membrane clocks.

PMID- 30092495
TI  - Capacity for evidence-informed policymaking across Europe: development and
      piloting of a multistakeholder survey.
AB  - OBJECTIVES: Evidence-informed policymaking (EIP) is increasingly viewed as a
      complex endeavour that requires integration of research evidence with available
      resources and the preferences of those affected by the policy. The first
      technical expert meeting to enhance EIP in the World Health Organization (WHO)
      European Region identified the scope to develop and conduct a survey to gather
      insights into the generation, translation and application of research evidence
      across the region. This article describes the process of developing and piloting
      a multistakeholder survey (promoted and technically supported by WHO/Europe) on
      the topic of capacity for EIP. STUDY DESIGN: Rapid review and pilot cross
      sectional survey. METHODS: A survey instrument was developed based on findings
      from the published literature and refined with input from EIP experts/champions.
      The online survey was then piloted using various recruitment strategies designed
      to maximise its reach among the key target groups (senior researchers, knowledge
      brokers and members of civil society). RESULTS: The rapid review revealed a clear
      gap in the evidence base in relation to broader surveys of capacity for EIP, as
      opposed to evidence-based practice at an individual level. Thirteen responses to
      the pilot survey were received from individuals in 10 European countries.
      Reported barriers to EIP included a lack of understanding among policymakers and
      a lack of interaction with researchers. There were examples of efforts to enhance
      capacity for EIP, both at region or country level and through membership of
      international networks and collaborations. However, few examples were given of
      the application and impact of research evidence on the policymaking process.
      CONCLUSION: This research has demonstrated the feasibility of developing and
      piloting a multicountry, multistakeholder survey to generate better understanding
      of evidence use in health policymaking. Next steps include incorporating the
      lessons learned into a revised version of the survey to be implemented with all
      53 WHO/Europe Member States.

PMID- 30092496
TI  - Deletion 101 residue at caveolin-1 scaffolding domain peptides impairs the
      ability of increasing heme oxygenase-1 activity.
AB  - OBJECTIVE: Resident alveolar macrophages (AMs) are activated and release
      proinflammatory mediators and chemokines during acute lung injury. We have
      previous reported that caveolin-1 (Cav-1) scaffolding domain (CSD) peptide
      inhibited the proinflammatory cytokines expression by up-regulating heme
      oxygenase-1 (HO-1) activity. In this study, we aimed to investigate the effect of
      residue R101 in CSD peptide on the activity of HO-1 in AMs. METHODS: The binding
      mode between HO-1 and CSD peptides (WT CSD and Delta101 CSD truncation peptides)
      was analyzed and the free energy was calculated. The inflammatory genes and
      M1/M2macrophage polarization-associated genes expression were measured by real
      time PCR. The activities of HO-1 were determined by the spectrophotometical
      method. Western blot analyzed the content of Cav-1, HO-1, IkappaB and MAPK
      signals (phosphorylated ERK, JNK and p38 MAPK). RESULTS: Delta101CSD peptide
      could bind to HO-1 protein and to disrupt the interaction of HO-1 and Cav-1.
      However, Delta101CSD peptide had lower activity of HO-1 in LPS-treated AMs
      compared with WT CSD. The expression of IL-1beta and MCP-1 and NO content were
      decreased by WT CSD peptide in LPS treated AMs. However, only MCP-1 expression
      and NO content were downregulated byDelta101CSD peptide. Meanwhile, compared with
      those in LPS + hemin + WT CSD group, the mRNA expression of TNF-alpha, Cd86, IL
      12b and NOS2 significantly increased while expression of IL10, Arg1 and CD163
      significantly decreased in LPS + hemin + Delta101CSD group. The effect of WT CSD
      peptide on the inhibition of MAPK signaling pathway were stronger than Delta101
      CSD peptide evidenced by the level of phosphorylated ERK, JNK and p38 MAPK.
      CONCLUSION: Deletion of residue R101 impairs the ability of CSD peptide to
      increase HO-1 activity and to dampen inflammatory response in LPS-challenged rat
      AMs.

PMID- 30092497
TI  - Low estradiol is linked to increased skin conductance, but not subjective anxiety
      or affect, in response to an impromptu speech task.
AB  - Low estradiol is associated with impaired extinction of conditioned physiological
      fear responses (e.g. skin conductance) in females. As fear extinction is the
      laboratory basis of exposure therapy for anxiety disorders, it has been
      speculated that estradiol may be related to the effectiveness of treatment for
      anxiety. The present study extended past research by examining whether estradiol
      is related to physiological and subjective fear responses during the impromptu
      speech task, where participants perform a surprise speech to camera. This task
      elicits psychosocial fear, and thus has relevance for social anxiety disorder
      (SAD). We used a quasi-experimental design with two groups of women: 39 naturally
      cycling women, and 19 women taking hormonal contraceptives. Based on the measured
      serum levels, naturally cycling women were further divided into women with higher
      vs. lower estradiol levels. Compared to those with higher estradiol, women with
      lower estradiol, and those using hormonal contraceptives (chronically suppressed
      estradiol) displayed higher speech-elicited skin conductance yet reported no
      differences in subjective anxiety or affect. Conversely, irrespective of
      estradiol status, compared to those with low self-reported social anxiety,
      participants with higher social anxiety exhibited greater subjective anxiety and
      affect, yet no differences in skin conductance. These results demonstrate that
      the relationship between estradiol and physiological fear responses extends to
      psychosocial tasks. However, the dissociations between physiological and
      subjective measures highlight the need to consider the relevance of different
      response outputs so that the potential impact of estradiol on the treatment of
      anxiety disorders can be better understood.

PMID- 30092499
TI  - Corrigendum to "HPV infection and breast cancer. Results of a microarray
      approach" [The Breast 40, (August 2018) 165-169].

PMID- 30092498
TI  - Management and 5-year outcomes in 9938 women with screen-detected ductal
      carcinoma in situ: the UK Sloane Project.
AB  - BACKGROUND: Management of screen-detected ductal carcinoma in situ (DCIS) remains
      controversial. METHODS: A prospective cohort of patients with DCIS diagnosed
      through the UK National Health Service Breast Screening Programme (1st April 2003
      to 31st March 2012) was linked to national databases and case note review to
      analyse patterns of care, recurrence and mortality. RESULTS: Screen-detected DCIS
      in 9938 women, with mean age of 60 years (range 46-87), was treated by mastectomy
      (2931) or breast conserving surgery (BCS) (7007; 70%). At 64 months median follow
      up, 697 (6.8%) had further DCIS or invasive breast cancer after BCS (7.8%) or
      mastectomy (4.5%) (p < 0.001). Breast radiotherapy (RT) after BCS (4363/7007;
      62.3%) was associated with a 3.1% absolute reduction in ipsilateral recurrent
      DCIS or invasive breast cancer (no RT: 7.2% versus RT: 4.1% [p < 0.001]) and a
      1.9% absolute reduction for ipsilateral invasive breast recurrence (no RT: 3.8%
      versus RT: 1.9% [p < 0.001]), independent of the excision margin width or size of
      DCIS. Women without RT after BCS had more ipsilateral breast recurrences (p <
      0.001) when the radial excision margin was <2 mm. Adjuvant endocrine therapy
      (1208/9938; 12%) was associated with a reduction in any ipsilateral recurrence,
      whether RT was received (hazard ratio [HR] 0.57; 95% confidence interval [CI]
      0.41-0.80) or not (HR 0.68; 95% CI 0.51-0.91) after BCS. Women who developed
      invasive breast recurrence had a worse survival than those with recurrent DCIS (p
      < 0.001). Among 321 (3.2%) who died, only 46 deaths were attributed to invasive
      breast cancer. CONCLUSION: Recurrent DCIS or invasive cancer is uncommon after
      screen-detected DCIS. Both RT and endocrine therapy were associated with a
      reduction in further events but not with breast cancer mortality within 5 years
      of diagnosis. Further research to identify biomarkers of recurrence risk,
      particularly as invasive disease, is indicated.

PMID- 30092501
TI  - A novel patient decision aid for aftercare in breast cancer patients: A promising
      tool to reduce costs by individualizing aftercare.
AB  - OBJECTIVE: A patient decision aid (PtDA), was developed to support breast cancer
      patients making choices about their aftercare. The aim of this pilot was to test
      the effects of the PtDA on Shared Decision Making (SDM), Decision Evaluation
      (DES) in patients, consultation time, choice of aftercare and hospital costs.
      METHODS: A prospective before-and-after study including a control (no PtDA-usage)
      and experimental group (PtDA-usage during consultation) was conducted in six
      hospitals. Patients were offered a choice between intensive (face-to-face
      consultations) and less intensive (telephonic or on demand consultations)
      aftercare. All patients filled out three validated questionnaires (baseline (T0),
      directly after the consultation (T1), three months later (T2)), assessing
      demographics (T0), SDM(T1) and DES (T1, T2). Hospital costs and choice of
      aftercare were assessed from the patients' files (T2). Effect sizes ( np2: 0.01 =
      small; 0.06 = medium; 0.14 = large; phi: 0.1 = small, 0.3 = medium, 0.5 = large)
      and p-values were calculated using both univariate and multivariate GLMs, a
      repeated measures GLM and chi-square-tests. RESULTS: A small improvement in SDM (
      np2 = 0.02) and an effect ( np2 = 0.10) on DES was found in the experimental
      group. Significantly more PtDA-users (51% vs. 29%, phi = 0.22) chose less
      intensive aftercare, leading to a small reduction of hospital costs (122 vs. 92
      Euro, np2 = 0.01), and a large increase in average consultation time (12.5 min;
      np2 = 0.29). CONCLUSION: This pilot study showed promising effects of the PtDA on
      SDM and hospital costs. The PtDA can be developed further to potentially reduce
      the increased consultation time.

PMID- 30092502
TI  - The effect of temporal concept on the automatic activation of spatial
      representation: From axis to plane.
AB  - Temporal concepts could be represented horizontally(X-axis) or vertically (Y
      axis). However, whether the spatial representation of time exists in the whole
      plane remains unclear. In this study, we investigated whether processing temporal
      concepts would automatically activate spatial representations in a whole plane
      without any guidance or cue. Participants first indicated whether a word was past
      related or future-related, then, they identified a target in different visual
      fields. In Experiment 1, the results demonstrated that past time mapped onto the
      left and top in a plane or axis, while future time mapped onto the right and
      bottom, with the horizontal effect being stronger than the vertical effect. In
      Experiment 2, an index of eye movement showed a similar data pattern. Thinking
      about temporal concepts activates spatial schema automatically without guidance
      or cue, and the time-space metaphor is represented not only as an axis but also
      as a whole plane. The results were discussed in terms of the possible cultural
      differences that made the Chinese participants tend to be more flexible in
      spatial representation of time because of their comprehensive thinking.

PMID- 30092500
TI  - T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast
      cancer.
AB  - BACKGROUND: We reported the results of an Italian large retrospective analysis
      that evaluated the effectiveness and safety of T-DM1 in 'field-practice' breast
      cancer patients. We performed a sub-analysis to investigate the clinical activity
      of T-DM1 in patients with brain metastases (BMs). METHODS: The records of 87
      adult women with HER2-positive breast cancer and BMs treated with T-DM1 were
      reviewed. Their clinical outcomes were compared with those of 216 patients
      without central nervous system (CNS) involvement. RESULTS: Response to T-DM1
      treatment in BMs was available for 53 patients in the BM group (60.9%): two
      patients reported a complete response (3.8%), 11 patients obtained partial
      response (20.7%; overall response rate: 24.5%), 16 patients had a stable disease
      (30.1%). Regarding extracranial disease, a total of 77 and 191 patients were
      evaluable for response in BM group and non-BM group, respectively. The overall
      response rate was 35.1% in the BM group and 38.3% in the non-BM group; disease
      control rate was 53.3% and 66.6%, respectively. At a median follow-up of 16
      months (range: 1-55), median cumulative progression-free survival (PFS) was 7
      months (95% CI: 5.4-8.6) in the BM group and 8 months (95% CI: 5.7-10.3) in the
      non-BM group. In the second-line setting, PFS was 5 (95% CI: 3.1-6.9) versus 11
      (95% CI: 7.1-14.9) months (p = 0.01). Overall survival was 14 months (95% CI:
      12.2-15.8) in the BM group and 32 months (95% CI: 24.4-39.6) in the non-BM group
      (p < 0.0001). CONCLUSIONS: T-DM1 is active in breast cancer patients with BMs.

PMID- 30092503
TI  - Topical folinic acid enhances wound healing in rat model.
AB  - PURPOSE: Folic acid is an essential vitamin participating in DNA synthesis and
      repair. Recently folic acid has been shown to stimulate DNA-repair capacity in
      dermal fibroblasts in response to injury. Thus, the present study aimed to
      investigate the effects of topical folinic acid, a 5-formyl derivative of
      tetrahydrofolic acid, on wound healing using rat wound model. MATERIALS AND
      METHODS: A rat wound model was established, and the wound healing was evaluated
      by macroscopic and histological analyses among vehicle control, 2.5% folinic
      acid, 1% folinic acid, and dexpanthenol treatment groups. While an image-analysis
      program was used to evaluate macroscopic wound closure, connective tissue
      properties, mast cell numbers, and the expressions of matrix metalloproteinase 1
      (MMP-1) and 9 (MMP-9) were evaluated by microscopy. RESULTS: The 2.5% folinic
      acid-treated group exhibited enhanced wound healing by increased
      reepithelialization, neo-vessel formation, inflammatory cell migration, collagen
      deposition and progressive mast cell increase. Furthermore, 2.5% folinic acid
      induced higher expressions of MMP-1 and MMP-9. CONCLUSIONS: Folinic acid enhances
      both macroscopic and microscopic wound healing in rat wound model.

PMID- 30092504
TI  - Frequency analysis and resonant operation for efficient capacitive deionization.
AB  - Capacitive deionization (CDI) performance metrics can vary widely with operating
      methods. Conventional CDI operating methods such as constant current and constant
      voltage show advantages in either energy or salt removal performance, but not
      both. We here develop a theory around and experimentally demonstrate a new
      operation for CDI that uses sinusoidal forcing voltage (or sinusoidal current).
      We use a dynamic system modeling approach, and quantify the frequency response
      (amplitude and phase) of CDI effluent concentration. Using a wide range of
      operating conditions, we demonstrate that CDI can be modeled as a linear time
      invariant system. We validate this model with experiments, and show that a
      sinusoid voltage operation can simultaneously achieve high salt removal and
      strong energy performance, thus very likely making it superior to other
      conventional operating methods. Based on the underlying coupled phenomena of
      electrical charge (and ionic) transfer with bulk advection in CDI, we derive and
      validate experimentally the concept of using sinusoidal voltage forcing functions
      to achieve resonance-type operation for CDI. Despite the complexities of the
      system, we find a simple relation for the resonant time scale: the resonant time
      period (frequency) is proportional (inversely proportional) to the geometric mean
      of the flow residence time and the electrical (RC) charging time. Operation at
      resonance implies the optimal balance between absolute amount of salt removed (in
      moles) and dilution (depending on the feed volume processed), thus resulting in
      the maximum average concentration reduction for the desalinated water. We further
      develop our model to generalize the resonant time-scale operation, and provide
      responses for square and triangular voltage waveforms as two examples. To this
      end, we develop a general tool that uses Fourier analysis to construct CDI
      effluent dynamics for arbitrary input waveforms. Using this tool, we show that
      most of the salt removal (~95%) for square and triangular voltage forcing
      waveforms is achieved by the fundamental Fourier (sinusoidal) mode. The frequency
      of higher Fourier modes precludes high flow efficiency for these modes, so these
      modes consume additional energy for minimal additional salt removed. This
      deficiency of higher frequency modes further highlights the advantage of DC
      offset sinusoidal forcing for CDI operation.

PMID- 30092505
TI  - Rapid oxidation of iodide and hypoiodous acid with ferrate and no formation of
      iodoform and monoiodoacetic acid in the ferrate/I-/HA system.
AB  - Toxic and odorous iodinated disinfection byproducts (I-DBPs) could form in the
      chemical oxidation of iodine-containing water. A critical step for controlling
      the hazardous I-DBPs is to convert the iodine species into stable and harmless
      iodate (IO3-) while inhibiting the accumulation of highly reactive hypoiodous
      acid (HOI). Herein, the oxidation of I- and HOI with ferrate was investigated,
      and the formation profile of HOI was determined based on 2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulfonate) (ABTS) coloring method through a stopped-flow
      spectrophotometer. The second-order rate constants (kapp) of ferrate with HOI
      decreased from 1.6 * 105 M-1s-1 to 8.3 * 102 M-1s-1 as the solution pH varied
      from 5.3 to 10.3, which were 7.5, 7.2 and 13.8 times higher than that of ferrate
      with I- at pH 6.0, 7.0 and 8.0, respectively. Compared with other oxidants such
      as ozone, hypochlorous acid, chloramine and potassium permanganate, ferrate would
      swiftly oxidize HOI formed in the I- oxidation process. For the ferrate oxidation
      of I-containing water, HOI was swiftly oxidized to IO3- from pH 5.0 to 9.0.
      Phosphate buffer promoted the oxidation of I- while inhibited the oxidation of
      HOI with ferrate. When 5 mgC/L of humic acids (HA) existed in the solution, no
      formation of iodoform and monoiodoacetic acid (MIAA) was observed in the
      oxidation of iodide (20 MUM) with ferrate (from 10 MUM to 80 MUM). These results
      suggested that ferrate oxidation could be an effective method for the control of
      I-DBPs in iodine-containing water treatment.

PMID- 30092506
TI  - Zeta potential determination with a microchannel fabricated in solidified
      solvents.
AB  - This paper proposes a simple and versatile method for the determination of the
      zeta potential of a channel wall and discusses the values measured for the
      surface of frozen solvents, which are not only of scientific interest but also of
      potential use for microfluidic platforms. The zeta potential of the solid surface
      is an important parameter for discussing its electrokinetic properties, the
      distribution and reaction of ions in an electric double layer, and the fluidic
      behavior in the space surrounded by the surface. While the zeta potential of
      colloidal matters can be determined from their electrophoretic mobility, it is
      often difficult to determine that of a bulk material. In this paper, the zeta
      potential of a microchannel fabricated in a frozen solvent is determined by
      measuring the apparent mobility of microparticles as the probe. The
      electrophoretic mobility of the microparticles has been measured in advance using
      microchip electrophoresis under various conditions. This approach allows us to
      determine the zeta potential of water-ice and frozen cyclohexane. We discuss the
      pH dependence of the zeta potential of ice and also effects of the NaCl
      concentration on that of ice and frozen cyclohexane.

PMID- 30092507
TI  - Hybrid membrane filtration-advanced oxidation processes for removal of
      pharmaceutical residue.
AB  - Reports of pharmaceuticals exist in surface water and drinking water around the
      world, indicate they are ineffectively remove from water and wastewater using
      conventional treatment technologies. The potential of adverse effect of these
      pharmaceuticals on public health and aquatic life, also their continuos
      accumulation have raised the development of water treatment technologies. Hybrid
      treatment processes like membrane filtration and advance oxidation processes
      (AOPs) are likely to give rise to efficient simultaneous degradation and
      separation mechanisms. Conventional membrane filtration techniques can remove the
      majority of contaminants, but the smallest, undegraded, and stabilized
      pharmaceutical wastes persist in the treated water. After some 20 years,
      researchers have recognized the important role of AOPs in the treatment of
      pharmaceutical wastewater because these technologies are capable of oxidizing
      recalcitrant, toxic, and non-biodigradable compounds into numerous by-products
      and finally, inert end-products via the intermediacy of hydroxyl and other
      radicals. Evidently, membranes are subjected to the fouling phenomenon by the
      contaminants in wastewater, hence resulting in a reduction of clean water flux
      and increase in energy demand. In such situations, these membrane hybrid AOPs
      exert a complementary effect in the elimination of membrane fouling, thus
      enhancing the performance of the membrane. Therefore, in this review, we describe
      the basic aspects of the removal and transformation of certain pharmaceuticals
      via membranes and AOPs. In addition, information and evidences on membrane hybrid
      AOPs in the field of pharmaceutical wastewater treatment is also presented.

PMID- 30092508
TI  - Ionic liquid directed construction of foam-like mesoporous boron-doped graphitic
      carbon nitride electrode for high-performance supercapacitor.
AB  - Carbon materials with controllable hierarchically porous structure and high
      doping level are expect to exhibit superior energy storage performance when used
      as electrode materials for supercapacitors. Herein, we report the preparation of
      a novel foam-like boron-doped carbon nitride material with hierarchically porous
      structure and high doping contents of nitrogen (21.45 +/- 0.93 at%) and boron
      (6.46 +/- 0.60 at%). Due to the unique compositional and structural features,
      this material exhibits high energy storage performance, including a large
      specific capacitance of ~ 660.6 F g-1 at 0.1 A g-1 and a high capacitance
      retention after 10,000 cycles. This study can provide new ideas for the
      development of carbon based electrode materials with unique hierarchically porous
      structure and improved doping level.

PMID- 30092509
TI  - In-situ synthesis of amorphous H2TiO3-modified TiO2 and its improved
      photocatalytic H2-evolution performance.
AB  - Surface cocatalyst modification is considered as one of the most ideal strategies
      for improved photocatalytic H2-evolution activity of photocatalysts. It is quite
      important to develop new cocatalyst and to enhance the interfacial coupling
      between cocatalysts and photocatalysts with the aim of promoting the rapid
      transfer of photogenerated charge. In this work, amorphous H2TiO3 (a-H2TiO3)
      nanoparticles (ca. 1 nm), as a novel and effective hole cocatalyst, were
      homogeneously in-situ generated on TiO2 surface (the sample was referred as a
      H2TiO3/TiO2) via a first controllable surface reaction of TiO2 in a NaOH solution
      and the following ion-exchange reaction with HCl solution at room temperature.
      The resultant a-H2TiO3/TiO2 photocatalysts exhibited greatly enhanced
      photocatalytic H2-evolution performance compared with pure TiO2, which was mainly
      attributed to amorphous H2TiO3 nanoparticles as hole cocatalysts for rapid hole
      transfer. To further promote the photocatalytic activity of a-H2TiO3/TiO2,
      Ni(OH)2 as electron cocatalysts was loaded on the surface of a-H2TiO3/TiO2 to
      prepare the co-modified a-H2TiO3/TiO2/Ni(OH)2 photocatalyst. The results
      indicated that the H2-evolution performance of the a-H2TiO3/TiO2/Ni(OH)2
      photocatalyst was significantly higher than that of a-H2TiO3/TiO2 by a factor of
      66.7 due to the synergy of a-H2TiO3 and Ni(OH)2 cocatalysts. This study provides
      a strategic approach for enhanced H2-evolution activity by enhanced interfacial
      coupling between cocatalysts and photocatalysts.

PMID- 30092510
TI  - Facile urea-assisted precursor pre-treatment to fabricate porous g-C3N4
      nanosheets for remarkably enhanced visible-light-driven hydrogen evolution.
AB  - Hydrogen generation photocatalyzed by low-cost graphite carbon nitride (g-C3N4)
      is a fascinating and effective route to solve energy crisis, but is mainly
      limited by the few reactive sites, low carrier separation efficiency and mediocre
      visible-light utilization. In this work, these limitations were tackled through a
      facile eco-friendly precursor pretreatment by tuning bulk g-C3N4 into porous
      structure. This pretreatment restricted agglomeration in the subsequent
      condensation and created more porous channels for charge carrier transfer and
      more surface active sites for reaction. The modified g-C3N4 has larger surface
      area, broader visible-light response, enhanced electron migration capacity and
      prolonged lifetime of photogenerated carriers. These well-amended g-C3N4
      nanosheets possess an average hydrogen evolution rate 5.7 times that of bulk g
      C3N4. This work affords a facile, eco-friendly and scalable strategy to design or
      synthesize other porous materials.

PMID- 30092511
TI  - The effect of amyloid-beta peptide on synaptic plasticity and memory is
      influenced by different isoforms, concentrations, and aggregation status.
AB  - The increase of oligomeric amyloid-beta (oAbeta) has been related to synaptic
      dysfunction, thought to be the earliest event in Alzheimer's disease
      pathophysiology. Conversely, the suppression of endogenous Abeta impaired
      synaptic plasticity and memory, suggesting that the peptide is needed in the
      healthy brain. However, different species, aggregation forms and concentrations
      of Abeta might differently influence synaptic function/dysfunction. Here, we have
      tested the contribution of monomeric and oligomeric Abeta42 and Abeta40 at 200 nM
      and 200 pM concentrations on hippocampal long-term potentiation and spatial
      memory. We found that, when at 200 nM, oAbeta40, oAbeta42, and monomeric Abeta42
      impaired long-term potentiation and memory, whereas only oAbeta42 200 pM enhanced
      synaptic plasticity and memory and rescued the detrimental effect due to
      depletion of endogenous Abeta. Interestingly, quantification of monomer-like and
      oligomer-like species carried out by transmission electron microscopy revealed an
      increase of the monomer/oligomer ratio in the oAbeta42 200 pM preparation,
      suggesting that the content of monomers and oligomers depends on the final
      concentration of the solution.

PMID- 30092512
TI  - Organic matter protection by kaolinite over bio-decomposition as suggested by
      lignin and solvent-extractable lipid molecular markers.
AB  - The formation of organo-mineral complexes is essential in organic matter (OM)
      stabilization. However, limited studies have been conducted to systematically
      examine the mineral influence on the decomposition of plant residuals at a
      molecular level. In this study, pine needles and chestnut leaves were mixed with
      kaolinite at the weight ratio of 5:1. The controls were plant tissues without
      kaolinite. All the samples were incubated in the laboratory for one year.
      Molecular markers, including lignin-derived phenols (e.g. Vanilly units, syringyl
      units and cinnamyl units) and solvent-extractable lipids (e.g. n-alkanoic acid, n
      alkanols and n-alkanes), were analyzed. The concentrations of lignin-derived
      phenols and lipid compounds were higher in the presence of kaolinite than without
      kaolinite. Lower degradation indexes, such as (Ad/Al)V (ratio of vanillic acid to
      vanillin) and CPI (carbon preference index of n-alkanoic acid and n-alkanes),
      were found in the kaolinite system. These results indicate that kaolinite reduced
      the OM decomposition. The addition of kaolinite also stabilized some
      carbohydrates from plants. Furthermore, the degradation of OM led to the
      generation of persistent free radicals, indicated by electron paramagnetic
      resonance (EPR) signals. The EPR signals were higher with than without kaolinite.
      We hypothesize that the adsorption of semiquinone or quinone radicals on
      kaolinite may limit their reaction with other OM moieties and thus extended their
      lifetimes. In addition to embedding OM in soil aggregates, our results provide
      direct evidence of another mineral protective mechanism of soil OM.

PMID- 30092513
TI  - Effects of metal and metalloid pollutants on the microbiota composition of feces
      obtained from twelve commercial pig farms across China.
AB  - Understanding the metal and metalloid contamination and microbiota composition of
      pig feces is an important step required to support the design and implementation
      of effective pollution control and prevention strategies. A survey was
      implemented in 12 locations across China to investigate the content of metals and
      metalloids, and the main composition of the microbial communities of commercially
      reared pigs during two growth periods, defined as the early (Q group) and the
      later fattening growth phases (H group). These data showed widespread Al, Mn, Cu,
      Zn, and Fe pollution in pig feces. The concentration of Zn in the Q group feces
      was nearly two times higher than the levels measured in the H group. The
      microbial composition of the Q group exhibited greater richness of operational
      taxonomic units (OTUs) and fewer bacteria associated with zoonotic diseases
      compared with the microbial composition of the H group. Spearman rank correlation
      analysis showed that Cu and northern latitudes had a significant positive effect
      on the richness of bacterial communities in pig feces. Zn and Cd exhibited the
      biggest impact on microbial community composition based on canonical
      correspondence analysis. Functional metagenomic prediction indicated that about
      0.8% genes present in the pig feces bacteria community are related to human
      diseases, and significantly more predicted pathogenic genes were detected in the
      H group than in the Q group. These results support the need to monitor heavy
      metal contamination and to control for zoonotic pathogens disseminated from pig
      feces in Chinese pig farms.

PMID- 30092514
TI  - Novel flexible Fenton-like catalyst: Unique CuO nanowires arrays on copper mesh
      with high efficiency across a wide pH range.
AB  - Free-standing and flexible Cu@CuO nanowires (NWs) mesh as an easily recycled
      Fenton-like catalyst is developed for the first time. Dense CuO nanowire arrays
      were uniformly grown on a copper mesh surface simply by wet etching accompanied
      with thermal dehydration. These dense CuO NWs provide a large specific area and
      therefore guarantee excellent catalytic performance toward the degradation of
      rhodamine B (RhB). With a k-value of 0.23 min-1, such a Cu@CuO NWs mesh is able
      to degrade 100% RhB in only 16 min. This Fenton-like catalyst is also appropriate
      for degrading other organic dyes, including crystal violet, methylene blue, and
      rhodamine 6G. Unlike the conventional Fenton catalyst implemented at a pH value
      around 3, the Cu@CuO NWs mesh could adapt to a wide pH range from 2.1 to 12.0.
      More intriguingly, the Cu@CuO NWs mesh with excellent flexibility could be easily
      recycled after catalysis, which is a significant advance compared to the
      previously reported Fenton catalysts in the form of powders or nanoparticles. In
      addition, the recycling performance of this Cu@CuO NWs mesh was also assessed. On
      the basis of electron spin resonance (ESR) results, O2- rather than OH is the
      main active species for the dye degradation by the Cu@CuO NWs mesh. With a
      marvelous combination of excellent flexibility, wide pH adaptation, and high
      efficiency, this easily recycled three dimensional Cu@CuO NWs architecture can
      afford new ideas for the Fenton chemistry.

PMID- 30092515
TI  - Influence of deep water formation by open-sea convection on the transport of low
      hydrophobicity organic pollutants in the NW Mediterranean Sea.
AB  - The significance of the offshore vertical convection currents in the transport
      and sinking of water-soluble organic pollutants into marine deep basins has been
      evaluated. For this purpose, sediment cores were collected in the Gulf of Lion
      (GoL) at sites between 26 and 2330 m water depth. The top core layers were
      analyzed for aromatic and aliphatic hydrocarbons and organochlorine compounds.
      Organic compounds with logKAW (air water partition coefficient) between -2 and 
      4, e.g. lindane, PCB 28, PCB 52, phenanthrene, methylphenanthrenes,
      dimethylphenanthrenes, C14-C23n-alkanes, are found in higher concentrations or
      exhibit relative concentration increases in the sediments deposited in the
      continental rise as consequence of the open-sea convection processes associated
      with the formation of Western Mediterranean Deep Water (WMDW). In contrast, the
      organic pollutants with intermediate air-water distribution coefficients, logKAW
      between -2 and 0, and high octanol water distribution coefficients (logKow > 6),
      e.g. highly chlorinated PCBs, DDTs, DDEs, DDDs, C25-C35n-alkanes, and polycyclic
      aromatic hydrocarbons with molecular weight higher than 200, occur in association
      to sediment particles, which are mainly transported by the Northern current along
      the continental shelf forming the mud belt. The Rhone prodelta is therefore the
      area of the GoL showing the highest concentrations of this group of organic
      compounds, which are preferentially associated with water particles. Overall, the
      results show that vertical open-sea convection processes related with offshore
      formation of WMDW may have an important role in the transport and accumulation of
      water soluble pollutants to deep marine environments of the GoL (>2000 m water
      depth).

PMID- 30092517
TI  - How human activities in commercial areas contribute to phthalate ester pollution
      in street dust of Taiwan.
AB  - : Exposure to phthalate esters (PAEs) poses health risks to humans. Much research
      has been performed evaluating PAE levels in foodstuffs, river sediment and
      drinking water, but little attention has been paid to their presence in urban
      outdoor environments where human activities are highly intense. Here we evaluated
      PAE presence and distribution in street dust in Kaohsiung, the most
      industrialized city in Taiwan. Our results showed that PAEs were ubiquitous in
      fifty-two street-dust samples (levels of total PAEs 5.4-989.2 mg kg-1). Di-(2
      ethylhexyl) phthalate was the most abundant congener observed and made up 85.0%,
      79.7%, and 97.2% of the total PAEs found in industrial, residential and
      commercial areas, respectively. PAE levels in street dust in commercial areas
      (night markets) were significantly higher, suggesting a higher risk of
      contamination on people present in these areas (H value > chiU2). In residential
      and commercial areas, the higher the intensity of human activity, the higher the
      PAE content observed. PAE content decreased progressively from the center to the
      outskirts of the Houjing night market, suggesting that the increased human and
      consumer activities inside this commercial hotspot were the main PAE source in
      street dust. Children had higher estimated daily intakes (DIs) than adults and
      dermal absorption contributed more to these levels than oral ingestion. Although
      all calculated DIs were below referenced danger thresholds, street dust PAEs in
      the area should remain an environmental concern especially since night markets
      play an important role in Taiwanese/Asian culture and economy. Contrary to other
      studies, PAEs in this study were found less related to industrial manufacturing
      activities but highly linked to commercial activities. These findings are
      relevant for future pollution prevention efforts dedicated to mitigating public
      exposure to PAEs. MAIN FINDINGS: PAE levels in street dust are related to
      commercial activities. Night markets, an important commercial activity in Taiwan,
      were found to contribute considerably to PAE contamination in street dust.

PMID- 30092516
TI  - Detection of illicit sand mining and the associated environmental effects in
      China's fourth largest freshwater lake using daytime and nighttime satellite
      images.
AB  - Illegal sand mining activities are rampant in coastal and inland water around the
      world and result in increased water turbidity, reduced water transparency, damage
      to fish spawning sites and adverse effects on the health of aquatic ecosystems.
      However, many sand dredging vessels hide during the day and work at night,
      rendering conventional monitoring measures ineffective. In this study, illegal
      sand dredging activities and the associated aquatic environmental effects were
      investigated in Lake Hongze (the fourth largest freshwater lake in China) using
      both conventional daytime satellite data, including MODIS/Aqua and Landsat TM/ETM
      data as well as VIIRS Day/Night Band (DNB) nighttime light (NTL) data, the
      following results were obtained. (1) The Landsat data revealed that sand dredging
      vessels first appeared in February 2012 and their number (monthly average: 658)
      peaked in 2016, and sand dredging stopped after March 2017. (2) The VIIRS NTL
      data were satisfactory for monitoring nighttime illegal dredging activities, and
      they more accurately reflected the temporal and spatial distribution
      characteristics of dredging vessels due to their high frequency. (3) Observations
      from the MODIS data acquired since 2002 showed three distinct stages of changes
      in the suspended particulate matter (SPM) concentrations of Lake Hongze that were
      consistent with the temporal distributions of sand dredging vessels. (4) The
      contribution of dredging vessels to the increases in SPM concentration was
      quantitatively determined, and nighttime sand dredging activities were found to
      have disturbed the waters more significantly. (5) The effectiveness of government
      measures implemented at various stages to control illegal sand dredging
      activities were scientifically evaluated. This study provides technological
      support for government monitoring and the control of illegal sand dredging
      activities and can serve as a valuable reference for water bodies similar to Lake
      Hongze worldwide.

PMID- 30092518
TI  - Identify driving forces of MBR applications in China.
AB  - During the last two decades, MBR applications in China grow exponentially with
      the first pilot test of 10 m3/d in 1999 and the first application with capacity
      of 110,000 m3/d commissioned in 2009. It is critical to examine the drivers of
      MBR applications in China, which can provide sound scientific basis for future
      development of MBR applications. This study summarized the historical development
      of MBR applications and analyzed the driving forces by survey, literature review
      and interviews with MBR suppliers. The results showed that: (1) technical
      advantages of MBR and public policy related to water resources and environment
      promoted MBR beyond lab and pilot test into wide commercial applications in
      China; (2) petrochemical industry needs for wastewater treatment and reuse
      promoted medium-scale MBRs as public policy and regulation on water resources and
      environment tightens; (3) when the breakthrough of capacity of a single project
      above 10 thousand m3/d, the Green Olympic Games and Asian Games and tightening
      effluent regulations in environmentally sensitive areas incentivized MBR
      applications; and (4) the emergence of 100,000 m3/d MBR was mainly stimulated by
      water resources stress. Water resources stress and public policy related on
      resources and the environment are the primary driving forces in the last several
      decades. The future drivers of MBR applications in China appear to be decreasing
      operation cost.

PMID- 30092519
TI  - Lead exposure biomarkers in the Common Loon.
AB  - Lead in fishing tackle is a significant source of exposure to the environment,
      wildlife, and potentially humans. Common Loons (Gavia immer) are exposed to lead
      by eating fish which have lead tackle, or ingesting fishing weights or spent
      ammunition when they ingest small stones to aid in digestion. Blood lead is
      traditionally used as a biomarker of exposure in loons, but it only reflects
      recent exposures. Cumulative exposure measured via bone lead may better reflect
      the overall health of loons and their aquatic habitat. This study compared a
      portable x-ray fluorescence (XRF) device for measurement of bone lead with and
      without tissue overlying the bone on loon cadavers with measurements made by
      inductively coupled plasma mass spectrometry (ICP-MS) of different tissues from
      the loons. For this study we had 75 bone samples, 19 body fluid samples, and 17
      liver lead samples. We found significant correlations between portable XRF bone
      lead measurements made with overlying tissue and ICP-MS measures of bone lead (R
      = 0.88), body fluid lead (R = 0.65), and liver lead (R = 0.71). Bone lead was
      found to be higher in loons collected from non-coastal regions. In assessing lead
      related cause of death, bone lead proved more predictive than liver lead. Future
      studies should investigate the value of these biomarkers for both aquatic health
      and loon health to further validate our findings.

PMID- 30092520
TI  - Particle bound pollutants in rivers: Results from suspended sediment sampling in
      Globaqua River Basins.
AB  - Transport of hydrophobic pollutants in rivers such as polycyclic aromatic
      hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and heavy metals is often
      facilitated by suspended sediment particles, which are typically mobilized during
      high discharge events. Suspended sediments thus represent a means of transport
      for particle related pollutants within river reaches and may represent a suitable
      proxy for average pollutant concentrations estimation in a river reach or
      catchment. In this study, multiple high discharge/turbidity events were sampled
      at high temporal resolution in the Globaqua River Basins Sava (Slovenia, Serbia),
      Adige (Italy), and Evrotas (Greece) and analysed for persistent organic
      pollutants such as PAHs (polycyclic aromatic hydrocarbons) or PCBs
      (polychlorinated biphenyls) and heavy metals. For comparison, river bed sediment
      samples were analysed as well. Further, results are compared to previous studies
      in contrasting catchments in Germany, Iran, Spain, and beyond. Overall results
      show that loadings of suspended sediments with pollutants are catchment-specific
      and relatively stable over time at a given location. For PAHs, loadings on
      suspended particles mainly correlate to urban pressures (potentially diluted by
      sediment mass fluxes) in the rivers, whereas metal concentrations mainly display
      a geogenic origin. By cross-comparison with known urban pressure/sediment yield
      relationships (e.g. for PAHs) or soil background values (for metals)
      anthropogenic impact - e.g. caused by industrial activities - may be identified.
      Sampling of suspended sediments gives much more reliable results compared to
      sediment grab samples which typically show a more heterogeneous contaminant
      distribution. Based on mean annual suspended sediment concentrations and
      distribution coefficients of pollutants the fraction of particle facilitated
      transport versus dissolved fluxes can be calculated.

PMID- 30092521
TI  - Environmental variables better explain changes in potential nitrification and
      denitrification activities than microbial properties in fertilized forest soils.
AB  - Because of increases in atmospheric nitrogen (N) deposition worldwide, nutrient
      imbalances and phosphorus (P) limitations in soil are aggravated, with the result
      that P fertilizer applications to terrestrial ecosystems worldwide may increase.
      Nitrification and denitrification in soil are major sources of nitrous oxide
      emissions, especially in soils treated with fertilizers. However, few researchers
      have studied how forest soils respond to nutrient additions, so we are not sure
      how the potential nitrification and denitrification activities (PNA and PDA,
      respectively) and microbial communities involved in these processes might respond
      when N and P are added to temperate and subtropical forest soils. We investigated
      how the PNA, PDA, the abundances and community compositions of nitrifiers and
      denitrifiers, and environmental properties, including soil pH, soil total and
      dissolved organic carbon, total and available N and phosphorus P, changed when N
      and/or P were added to subtropical and temperate forest soils. We quantified the
      abundance, and analyzed the composition, of functional marker genes of nitrifiers
      (ammonia-oxidizing bacteria and archaea amoA) and denitrifiers (nirK and nirS)
      using quantitative PCR and sequencing, respectively. We found that the PNA and
      PDA in the subtropical soil increased when P was added and PNA in the temperate
      forest soil increased when either N or P was added. The PNA and PDA were
      positively correlated with the abundance of ammonia-oxidizing bacteria and nirK
      denitrifiers, respectively, in the subtropical forest soil but were not
      correlated with changes in corresponding community compositions in either of the
      forest soils. The soil total N to total P ratio explained most of the
      variabilities in the PNA and PDA in the subtropical forest soils, and the soil
      exchangeable ammonium concentrations and pH were the main controls on the PNA and
      PDA, respectively, in the temperate forest soils. Our results indicate that soil
      environmental conditions have more influence on variations in the PNA and PDA in
      forest soils fertilized with N and P than the corresponding microbial properties.

PMID- 30092522
TI  - A standard-value-based comparison tool to analyze U.S. soil regulations for the
      top 100 concerned pollutants.
AB  - Residential surface soil contamination is often addressed by the use of
      regulatory guidance values (RGVs), which specify the maximum allowed
      concentration that can be present without prompting a regulatory action. In the
      U.S., there are at least 72 jurisdictions, including national, state, and
      regional, that have published guidance values for one or more of the one hundred
      most frequently regulated chemicals. A standard-value-based comparison tool in
      this study is developed to analyze values from 40 states and from the U.S.
      Environmental Protection Agency (U.S. EPA). The comparison tool can help evaluate
      the completeness of RGV sets, quantify the average deviation of RGVs from
      worldwide central tendencies, and measure the overall difference between the
      numbers of RGVs above and below central tendencies. The pollutants considered in
      this study include benzidines/aromatic amines, dioxins and polychlorinated
      biphenyls (PCBs), hydrocarbons, inorganic substances,
      nitroamines/ethers/alcohols, organophosphates and carbamates, pesticides,
      phenols/phenoxy acids, phthalates, and volatile organic compounds. Based on
      completeness and comparisons of order of magnitude variations, five types of
      scores are generated. The results from the completeness scores indicate that some
      states lack soil RGVs for the top 100 concerned pollutants. The results from the
      comparison scores indicate that some jurisdictions have provided the RGVs
      averagely deviating from worldwide central tendencies and U.S. EPA scores by over
      two orders of magnitude, which might be beyond the risk model variabilities and
      increase human health risks. Hopefully, the regulatory comparison tool developed
      in this study will help risk assessors and regulatory scientists to better
      evaluate soil standards and protect public health.

PMID- 30092523
TI  - Concentrations and congener group profiles of short- and medium-chain chlorinated
      paraffins in animal feed materials.
AB  - Chlorinated paraffins (CPs) are ubiquitous environmental pollutants that are
      lipophilic and can accumulate in the food chain. Animal-derived products are
      predominant contributors to human CP exposure. CPs in animal feed might
      accumulate in domestic animals through dietary exposure, leading to potential
      contamination of animal-derived food products and human health risks. However,
      information on the presence of CPs in animal feed materials is scarce. In this
      study, 16 animal feed material samples were collected in China in 2016. Thirteen
      of the samples were of animal origin and three were of plant origin. The
      concentrations and carbon and chlorine congener group profiles of shortchain
      chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in
      these animal feed materials were investigated. The concentrations of SCCPs were
      higher than those of MCCPs in all of the samples. The SCCP concentration range
      was 120 to 1700 ng/g (mean 640 ng/g), and the MCCP concentration range was 6.4 to
      260 ng/g (mean 78 ng/g). Fish meal had the highest SCCP and MCCP concentrations.
      The lowest SCCP and MCCP concentrations were detected in peanut meal and whey
      powder, respectively. The concentrations of SCCPs and MCCPs varied among the
      types of animal feed materials. SCCP and MCCP concentrations also varied among
      samples of the same type of animal feed material. Relatively high concentrations
      of SCCPs and MCCPs were detected in feed materials of animal origin. The
      predominant congener groups in the animal feed materials were C10-11Cl6-7 for
      SCCPs and C14Cl7 for MCCPs. The carbon and chlorine congener group profiles of
      SCCPs indicated that SCCP contamination in the animal feed materials might arise
      from commercial CP mixtures.

PMID- 30092524
TI  - Dehalogenation of trichloroethylene vapors by partially saturated zero-valent
      iron.
AB  - The reduction of trichloroethylene (TCE) in gas phase by different types of
      granular zero-valent iron (Fe0) was examined in anaerobic batch vapor systems
      performed at room temperature. Concentrations of TCE and byproducts were
      determined at discrete time intervals by analysis of the headspace vapors.
      Depending on the type of iron used, reductions of TCE gas concentration from 35%
      up to 99% were observed for treatments of 6 weeks. In line with other
      experimental studies performed with aqueous solutions, the particle size was
      found to play a key role in the reactivity of the iron. Namely an increase of the
      TCE removal up to almost 3 times was observed using iron powders with particle
      size lower than 425 MUm compared to iron powders with particle size lower than
      850 MUm. The manufacturing process of the iron powder was instead found to play
      only a limited role. Namely, no significant differences were observed in the TCE
      reduction by Fe0 obtained using an iron powder attained by water atomization and
      sieving compared to the removal achieved using an iron powder subjected to a
      further annealing processes to reduce the content of oxides. Conversely, the
      pretreatment of the iron powder with HCl was found to enhance the reactivity of
      the iron. In particular, by washing the iron powder of 425 MUm with HCl acid 0.1
      M the reduction of TCE after 6 weeks of treatment increase from approximately 80%
      for the as received material to >99% for the pretreated iron powder. We also
      performed tests at different humidity of the iron observing that not statistical
      differences were obtained using a water content of 10% or 50% by weight. In all
      the experiments, the only detectable byproducts of the reactions were C4-C6
      alkenes and alkanes that can be attributed to a hydrogenation of the CCl bond.

PMID- 30092525
TI  - Degradation and defluorination of 6:2 fluorotelomer sulfonamidoalkyl betaine and
      6:2 fluorotelomer sulfonate by Gordonia sp. strain NB4-1Y under sulfur-limiting
      conditions.
AB  - 6:2 fluorotelomer sulfonamidoalkyl betaine (6:2 FTAB) is a major component of
      aqueous film-forming foams (AFFFs) used for firefighting and is frequently
      detected, along with one of its suspected transformation products, 6:2
      fluorotelomer sulfonate (6:2 FTSA), in terrestrial and aquatic ecosystems
      impacted by AFFF usage. Biochemical processes underlying bacterial biodegradation
      of these compounds remain poorly understood due to a lack of pure culture
      studies. Here, we characterized the water-soluble and volatile breakdown products
      of 6:2 FTSA and 6:2 FTAB produced using Gordonia sp. strain NB4-1Y cultures over
      seven days under sulfur-limited conditions. After 168 h, 99.9% of 60 MUM 6:2 FTSA
      was degraded into ten major breakdown products, with a mol% recovery of 88.2,
      while 70.4% of 60 MUM 6:2 FTAB was degraded into ten major breakdown products,
      with a mol% recovery of 84.7. NB4-1Y uses two pathways for 6:2 FTSA metabolism,
      with 55 mol% of breakdown products assigned to a major pathway and <1.0 mol%
      assigned to a minor pathway. This work indicates that rapid transformation of 6:2
      FTSA and 6:2 FTAB can be achieved under controlled conditions and improves the
      bacterial metabolism of these compounds.

PMID- 30092526
TI  - Increasing aridity affects soil archaeal communities by mediating soil niches in
      semi-arid regions.
AB  - Soil archaea plays a vital role in the functioning of dryland ecosystems, which
      are expected to expand and get drier in the future as a result of climate change.
      However, compared with bacteria and fungi, the impacts of increasing aridity on
      archaea in these ecosystems remain largely unknown. Here, soil samples were
      collected along a typical aridity gradient in semi-arid regions in Inner
      Mongolia, China, to investigate whether and how the increasing aridity affects
      archaeal communities. The results showed that archaeal richness linearly
      decreased with increasing aridity. After partialling out the effects of soil
      properties based on partial least squares regression, the significant aridity
      richness relationship vanished. The composition of archaeal communities was
      distributed according to the aridity gradient. These variations were largely
      driven by the changes in the relative abundance of Thaumarchaeota, Euryarchaeota
      and unclassified phyla. Niche-based processes were predominant in structuring the
      observed archaeal aridity-related pattern. The structural equation models further
      showed that aridity indirectly reduced archaeal richness through improving soil
      electrical conductivity (EC) and structured community composition by changing
      soil total nitrogen (TN). These results suggested that soil salinization and N
      losses might be important mechanisms underlying the increasing aridity-induced
      alterations in archaeal communities, and highlighted the importance of soil
      niches in mediating the indirect impacts of increasing aridity on archaea.

PMID- 30092527
TI  - Heteroaggregation and sedimentation of graphene oxide with hematite colloids:
      Influence of water constituents and impact on tetracycline adsorption.
AB  - Because the transport of graphene oxide nanosheets (GO) from water to sediments
      is influenced by their heteroaggregation and sedimentation with natural colloids,
      knowledge on the interdependence of heteroaggregation and sedimentation for GO is
      needed to gain a better insight on the environmental fate of these nanosheets.
      However, this phenomenon is still not well understood. In this study, the
      heteroaggregation and sedimentation behaviors of GO with hematite nanoparticles
      (HemNPs) were investigated at various conditions. It has been found that
      negatively charged GO rapidly underwent heteroaggregation with positively charged
      HemNPs, leading to the sedimentation of GO. Significant sedimentation occurred
      when the net charge of the GOHemNP mixture was close to zero. The presence of
      various natural organic matters suppressed the sedimentation of the
      heteroaggregates through various mechanisms. Specifically, adsorption of humic
      acid and alginate reversed HemNP surface charge from positive to negative,
      leading to a slow sedimentation of the GOHemNP mixtures due to the increase in
      nanoparticle electrostatic repulsion. Adsorption of bovine serum albumin raised
      steric hindrance effect between GO and HemNP, which in turn inhibited their
      heteroaggregation and sedimentation. At high ionic strength conditions, the
      sedimentation of GO and HemNP was enhanced, possibly through the combination of
      homo- and hetero-aggregation. At elevated pH, the heteroaggregates were partially
      disaggregated, probably due to the weakening of GOHemNP bonds as the surface
      charges of these nanomaterials became more negative. Moreover, heteroaggregation
      of GO with HemNP likely to occupy the adsorption sites on GO surfaces, thus
      greatly reduced the adsorption of tetracycline on GO. These findings highlighted
      the important roles of natural colloids on the fate and transport of GO, together
      with the importance of heteroaggregation on the adsorption of co-existing
      pollutants to GO in natural aquatic environments.

PMID- 30092528
TI  - Shift from feeding to sustainably nourishing urban China: A crossing-disciplinary
      methodology for global environment-food-health nexus.
AB  - Dietary change is a win-win opportunity to address the nexus of health and the
      environment. To prevent city dwellers from developing non-communicable diseases,
      in 2013, China updated the 2000 version of nutrition-based dietary reference
      intake (DRI) guidelines. However, whether the DRI guidelines have a positive
      effect on the environment is not well understood. Here, we explored the
      systematic effects of urbanization on China's health and environmental nexus
      based on survey data. Then, we optimized the diets of 18 age-gender groups to
      reduce carbon emissions, water consumption, and land use while meeting the
      healthy nutrition goals of both DRI guidelines. The results showed that the
      optimal diets based on the DRI 2013 outperformed these on DRI 2000 in improving
      China's environmental sustainability, although these diets did not always perform
      better at an individual scale. Our findings suggest that dietary changes can
      reduce carbon, water, and ecological footprints by 24%, 15%, and 22% in 2050,
      respectively; however, the differences in age-specific and gender-specific health
      goals cannot be neglected.

PMID- 30092529
TI  - One-pot synthesis of catalytic molybdenum based nanocomposite nano-fiber
      membranes for aerosol air remediation.
AB  - The development of fibrous air filters exhibiting high air filtration efficiency,
      low energy consumption, and self-cleaning properties is a critical challenge to
      generate the next generation of resilient air filtration systems. Nano-fibrous
      mats typically exhibit higher particle capture efficiency but may also lead to
      higher airflow resistance compared to macro-fibrous materials due to their
      tighter structure. In this paper, novel catalytic membranes mats were fabricated
      through a one-pot synthesis from ammonium tetrathiomolybdate (ATTM) doped
      poly(acrylonitrile) (PAN) nanofibers for sub-micron diameter aerosol particle
      removal. The presence of ATTM as a dopant in conjunction with a PAN polymeric
      matrix was found to not only enhance the air filtration performance by increasing
      aerosol particle removal down to 300 nm, but also increase the photocatalytic
      properties of the PAN material. The enhanced separation properties compared to
      bare polymeric PAN nanofibrous membranes were attributed to surface
      nanotexturation of the fibers, leading to protrusions and pores across the nano
      fiber structures, thus leading to more permeable and lightweight membranes with
      higher particle capture capacities. The samples were benchmarked against
      commercial glass fiber air filters and found to offer higher filtration
      efficiency, lower pressure drop, and higher quality factor than the commercial
      filters. Specifically, the quality factors of the catalytic nano-fiber membranes
      were found to be up to four times higher than that of the benchmarked commercial
      air filters for PM2.5 particles, while two times higher for 300 nm sized
      contaminants. The presence of the ATTM across the PAN matrix was also found to
      enhance the photocatalytic activity of the membranes by up to 130% compared to
      the bare PAN reference nanofibers. This novel strategy opens avenues to
      engineering advanced multifunctional catalytic membranes, to capture toxic
      particulate matter from air while offering self-cleaning properties when exposed
      to sunlight.

PMID- 30092530
TI  - Enhanced removal of organic contaminants in water by the combination of
      peroxymonosulfate and carbonate.
AB  - In this study, a favorable CO32-/PMS system for efficient degradation of organic
      contaminants (acid orange 7 (AO7), acetaminophen, para-aminobenzoic acid, phenol,
      methylene orange, methylene blue) in water was firstly reported. Under optimal
      conditions, the decolorization ration of AO7 was 100% within 40 min. Data fitting
      showed that the AO7 decolorization could be described by the pseudo-first-order
      kinetics, and the rates constant values ranging from 0.0006 to 0.2297 min-1
      depending on the operating parameters (initial PMS, CO32-, AO7 concentrations).
      Radical scavenging studies revealed that superoxide anion radical (O2-) and
      singlet oxygen (1O2) rather than sulfate (SO4-) nor hydroxyl (HO) were the
      dominant oxidants might be responsible for AO7 degradation. The presence of NO3-,
      HPO42- and low concentration of Cl-, NO2-, HCO3-, H2PO4-, HA had no significantly
      effect on the decolorization of AO7. Adding a higher Cl- concentration displayed
      favorable effects on the removal efficiencies of AO7, but adding a higher NO2-,
      HCO3-, H2PO4- and HA concentration apparently inhibited this process. The
      decolorization of AO7 was lower in wastewater in comparison to other natural
      waters and ultrapure water, which was probably due to the presence of higher
      concentration of colloids in wastewater. Nevertheless, up to 94.8%, 97.0% and
      85.1% of AO7 were degraded from the filtrate, permeate, and retentate phases of
      wastewater within 60 min, respectively. Consequently, CO32-/PMS would be
      promising for removal methodology for AO7 in wastewater containing considerable
      colloids. Finally, three intermediates were identified and degradation pathways
      of AO7 were proposed.

PMID- 30092531
TI  - Formation of disinfection by-products under influence of shale gas produced
      water.
AB  - Accidental spills and surface discharges of shale gas produced water could
      contaminate water resources and generate health concerns. The study explored the
      formation and speciation of disinfection by-products (DBPs) during chlorination
      of natural waters under the influence of shale gas produced water. Results showed
      the presence of produced water as low as 0.005% changed the DBP profile
      measurably. A shift to a more bromine substitution direction for the formation of
      trihalomethanes, dihaloacetic acids, trihaloacetic acids, and dihaloacetonitriles
      was illustrated by exploring the individual DBP species levels, bromine
      substitution factors, and DBP species fractions, and the effect was attributable
      to the introduction of bromide from produced water. The ratio of dichloroacetic
      and trichloroacetic acids also increased, which was likely affected by different
      bromination degrees at elevated bromide concentrations. Increasing blend ratios
      of produced water enhanced the formation of DBPs, especially the brominated
      species, while such negative effects could be alleviated by pre-treating the
      produced water with ozone/air stripping to remove bromide. The study advances
      understandings about the impacts of produced water spills or surface discharges
      regarding potential violation of Stage 2 DBP rules at drinking water treatment
      facilities.

PMID- 30092532
TI  - An ensemble forecast model of dengue in Guangzhou, China using climate and social
      media surveillance data.
AB  - BACKGROUND: China experienced an unprecedented outbreak of dengue in 2014, and
      the number of dengue cases reached the highest level over the past 25 years.
      There is a significant delay in the release of official case count data, and our
      ability to timely track the timing and magnitude of local outbreaks of dengue
      remains limited. MATERIAL AND METHODS: We developed an ensemble penalized
      regression algorithm (EPRA) for initializing near-real time forecasts of the
      dengue epidemic trajectory by integrating different penalties (LASSO, Ridge,
      Elastic Net, SCAD and MCP) with the techniques of iteratively sampling and model
      averaging. Multiple streams of near-real time data including dengue-related Baidu
      searches, Sina Weibo posts, and climatic conditions with historical dengue
      incidence were used. We compared the predictive power of the EPRA with the
      alternates, penalized regression models using single penalties, to
      retrospectively forecast weekly dengue incidence and detect outbreak occurrence
      defined using different cutoffs, during the periods of 2011-2016 in Guangzhou,
      south China. RESULTS: The EPRA showed the best or at least comparable performance
      for 1-, 2-week ahead out-of-sample and leave-one-out cross validation forecasts.
      The findings indicate that skillful near-real time forecasts of dengue and
      confidence in those predictions can be made. For detecting dengue outbreaks, the
      EPRA predicted periods of high incidence of dengue more accurately than the
      alternates. CONCLUSION: This study developed a statistically rigorous approach
      for near-real time forecast of dengue in China. The EPRA provides skillful
      forecasts and can be used as timely and complementary ways to assess dengue
      dynamics, which will help to design interventions to mitigate dengue
      transmission.

PMID- 30092533
TI  - High thermal stress responses of Echinolittorina snails at their range edge
      predict population vulnerability to future warming.
AB  - Populations at the edge of their species' distribution ranges are typically
      living at the physiological extreme of the environmental conditions they can
      tolerate. As a species' response to global change is likely to be largely
      determined by its physiological performance, subsequent changes in environmental
      conditions can profoundly influence populations at range edges, resulting in
      range extensions or retractions. To understand the differential physiological
      performance among populations at their distribution range edge and center, we
      measured levels of mRNA for heat shock protein 70 (hsp70) as an indicator of
      temperature sensitivity in two high-shore littorinid snails, Echinolittorina
      malaccana and E. radiata, between 1 degrees N to 36 degrees N along the NW
      Pacific coast. These Echinolittorina snails are extremely heat-tolerant and
      frequently experience environmental temperatures in excess of 55  degrees C when
      emersed. It was assumed that animals exhibiting high temperature sensitivity will
      synthesize higher levels of mRNA, which will thus lead to higher energetic costs
      for thermal defense. Populations showed significant geographic variation in
      temperature sensitivity along their range. Snails at the northern range edge of
      E. malaccana and southern range edge of E. radiata exhibited higher levels of
      hsp70 expression than individuals collected from populations at the center of
      their respective ranges. The high levels of hsp70 mRNA in populations at the edge
      of a species' distribution range may serve as an adaptive response to locally
      stressful thermal environments, suggesting populations at the edge of their
      distribution range are potentially more sensitive to future global warming.

PMID- 30092534
TI  - Expression patterns of heat shock protein genes in Rita rita from natural
      riverine habitat as biomarker response against environmental pollution.
AB  - River pollution is one of the principal environmental concerns and biomonitoring
      tools can play an important role in pollution assessment in the riverine
      environment. Heat shock proteins (Hsps) have been found to be suitable tools for
      monitoring stress response. In the present study, expression analyses of hsp
      genes (hsp27, hsp47, hsp60, hsp70, hsc70, and hsp90) and selected hsp-regulatory
      genes (hsf1, hyou1, ask1, jnk) were carried out by RT-qPCR in catfish Rita rita
      collected from selected stretches of river Ganga to investigate changes in their
      expression patterns as biomarker response. Water quality characteristics were
      measured in terms of physico-chemical characteristics (DO, BOD, COD, pH,
      conductivity), element profile (arsenic, mercury, cadmium, lead, chromium, zinc,
      copper) and persistent organic pollutants (POPs; HCH, DDT, aldrin, endosulphan,
      heptachlor). Water quality index was calculated and sampling sites were
      categorized as good/medium/bad. Multivariate analysis was carried out taking the
      water quality parameters and the fold changes in hsp gene expression as
      variables, which showed that hsp47 and hsp70b correlated well with BOD, an
      indicator of organic pollution. To identify the organic pollutant(s) which could
      be influencing the expression of hsps, again multivariate analysis was employed
      taking concentration of POPs and fold changes of hsps, which showed up-regulation
      of hsp47 and hsp70b (HSP72i) correlated well with concentrations of aldrin and
      HCH. Synergistic effects of these POPs could be responsible for the up-regulation
      of said hsps, although individually present in low concentration; thus,
      indicating synergistic effect of the POPs on hsp47 and hsp70b up-regulation as
      biomarker response.

PMID- 30092535
TI  - Association of urinary concentrations of phthalate metabolites with
      cardiometabolic risk factors and obesity in children and adolescents.
AB  - This study aimed to investigate the association of urinary concentration of
      phthalate metabolites with obesity and cardiometabolic risk factors in a
      pediatric population. This study was conducted in 2016 on 242 children and
      adolescents, aged 6-18 years, living in Isfahan, Iran. Urinary concentration of
      mono-butyl phthalate (MBP), mono-benzyl phthalate (MBzP), Mono-2-ethylhexyl
      phthalate (MEHP), Mono-methyl phthalate (MMP), Mono (2-ethyl-5-exohexyl)
      phthalate (MEOHP), and mono (2-ethyl-5hydroxyhexyl) phthalate (MEHHP) metabolites
      were determined. The association of these metabolites with obesity and
      cardiometabolic risk factors was examined using student t-test, linear and
      logistics regression tests. Of the 242 participants studied, 140 (57.9%) were
      girls and 102 (42.1%) were boys. The mean (SD) age of the population was 11.34
      (2.55) years and no significant difference existed in terms of age (p-value =
      0.374). MBzP, MBP, MMP were observed in urine samples of all subjects, and MEHP,
      MEOHP, and MEHHP were observed in 99.6, 95.87, and 96.28% of the subjects,
      respectively. Of the total participants, 15.2% (n = 37) were obese and 37.7% (n =
      92) were overweight. According to the logistic regression analysis, except MEOHP,
      all other pollutants were significantly associated with obesity (OR adjusted >1,
      p-value <= 0.002). A significant association existed between MBP and elevated
      blood pressure [OR crude in tertile3 = 4.87 (CI: 1.02-23.32), p-value = 0.024].
      MBzP and MEHP were significantly associated with obesity, elevated levels of
      triglyceride and blood pressure. Increase in MBzP metabolite in the 3rd tertile
      resulted to about 2.5-fold increase in triglyceride levels than the first tertile
      [OR multivariate adjusted = 2.7 (CI: 1.23-6.22)]. The findings of this study
      clearly showed the association between phthalate metabolites with obesity,
      cardiometabolic risk factors in children and adolescents, however further
      longitudinal studies are necessary to evaluate the clinical effects of this
      finding.

PMID- 30092536
TI  - Pollutant transport analysis and source apportionment of the entire non-point
      source pollution process in separate sewer systems.
AB  - Understanding pollutant transport process and source apportionment is critical to
      urban stormwater pollution mitigation. Previous studies have investigated
      transport and sources of road deposited sediments (RDS) and sewer sediments
      individually, and most of these studies focused on stormwater pollution in
      combined sewer systems. However, studies about pollutant transport and source
      apportionment of the entire urban non-point source pollution process in separate
      sewer systems are lacking. This study analyzed particle size distribution and
      chemical pollutants in five media during the entire pollutant process including
      RDS, roof runoff, road runoff, sewer sediments, and sewer runoff. The outcomes
      found that mass percentage of fine particles became greater during pollutant
      transport in stormwater runoff. According to transport characteristics, particles
      were grouped into three types: particles <20 MUm, 20-105 MUm, and >105 MUm.
      Particles <20 MUm had the highest mobility capacity and particles >105 MUm had
      the lowest mobility capacity, while mobility capacity of particles 20-105 MUm was
      uncertain. Pollutant concentrations in road runoff were significantly influenced
      by rainfall intensity and pollutant concentrations in sewer runoff could become
      lower during rainy seasons ignoring rainfall intensity. RDS was the main
      contributor of heavy metals while organic matter and nutrients were primarily
      contributed by sewer sediments. Roof runoff, road runoff and sewer sediments
      contributed 5.35%, 69.24% and 25.41% particles to urban receiving water,
      respectively. Based on the outcomes, several suggestions were given for
      stormwater management.

PMID- 30092537
TI  - Changes in hypopharyngeal glands of nurse bees (Apis mellifera) induced by pollen
      containing sublethal doses of the herbicide Roundup(r).
AB  - Decreasing pollinator populations worldwide has generated great concern and
      stimulated countless studies to understand the origin of colony losses. One main
      cause is the indiscriminate use of different pesticides, producing subtle
      negative effects on bee physiology and behavior. Royal jelly synthesized in the
      hypopharyngeal glands is an essential protein for feeding all individuals of the
      hive, especially the queen. Therefore, the present study aimed to determine the
      effect of sublethal concentrations of Roundup(r) on the hypopharyngeal glands of
      nursing workers, including its interference with the production of royal jelly.
      The herbicide was found to promote changes in the cellular ultrastructure of
      these glands, causing early degeneration of the rough endoplasmic reticulum and
      morphological and structural changes in the mitochondria. No changes were noted
      in the amount of royal jelly produced, but additional long-term studies are
      necessary to determine possible qualitative changes. This is the first study to
      evaluate the effect of Roundup(r) on the royal jelly-producing glands, showing
      that resultant alterations in these structures can trigger damage to the
      development and survival of bee colonies.

PMID- 30092538
TI  - Antioxidative response of Phanerochaete chrysosporium against silver nanoparticle
      induced toxicity and its potential mechanism.
AB  - Antioxidative response of Phanerochaete chrysosporium induced by silver
      nanoparticles (AgNPs) and their toxicity mechanisms were comprehensively
      investigated in a complex system with 2,4-dichlorophenol (2,4-DCP) and Ag+.
      Malondialdehyde content was elevated by 2,4-DCP, AgNPs, and/or Ag+ in
      concentration- and time-dependent manners within 24 h, indicating an increase in
      lipid peroxidation. However, beyond 48 h of exposure, lipid peroxidation was
      alleviated by upregulation of intracellular protein production and enhancement in
      the activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase
      (POD). Comparatively, POD played more major roles in cell protection against
      oxidative damage. Furthermore, the dynamic change in reactive oxygen species
      (ROS) level was parallel to that of oxidized glutathione (GSSG), and ROS levels
      correlated well with GSSG contents (R2 = 0.953) after exposure to AgNPs for 24 h.
      This finding suggested that elimination of oxidative stress resulted in depletion
      of reduced glutathione. Coupled with the analyses of anoxidative responses of P.
      chrysosporium under the single and combined treatments of AgNPs and Ag+, HAADF
      STEM, SEM, and EDX demonstrated that AgNP-induced cytotoxicity could originate
      from the original AgNPs, rather than dissolved Ag+ or the biosynthesized AgNPs.

PMID- 30092539
TI  - Green synthesis of mesoporous gamma-Al2O3 from coal fly ash with simultaneous on
      site utilization of CO2.
AB  - Mesoporous Al2O3 with crystalline framework walls has expanded all over the world
      due to the various potential applications especially in catalysis. Here, we
      develop a green and facile approach for the conversion of coal fly ash (CFA) into
      ordered mesoporous gamma-Al2O3. The practical and promising lime-sinter method
      was comprehensively studied for the extraction of aluminum from CFA as a first
      step. The extraction efficiency of aluminum could reach up to 87.42%, through
      calcining with CaCO3 at 1390 degrees C for 1 h and then dissolving in Na2CO3
      solution at 70 degrees C for 0.5 h. Combined with the urgent demand for CO2
      emission reduction, simulated purified flue gas was introduced to precipitate the
      Al(OH)3 precursors without structure-directing agents for just 1 h, followed by
      calcining at only 400 degrees C or 550 degrees C. A series of characterizations
      were conducted to discuss the effect of precipitation temperature and calcination
      temperature, resulting the superior product (Al2O3-65/550) with high surface area
      (230.3 m2 g-1), crystalline gamma-Al2O3 phase and ordered mesostructure. This
      proposed strategy, integrating the on-site recycling of CFA and utilization of
      CO2, appears to be promising for scalable production of mesoporous gamma-Al2O3.

PMID- 30092540
TI  - A unique case report of jejunoileal bypass reversal with review of the
      literature.
AB  - INTRODUCTION: Jejunoileal bypass (JIB) was an effective treatment for morbid
      obesity in the 1970s, but shortly after it fell out of favor due to horrific side
      effects, including liver failure, nephrolithiasis and drastic vitamin
      deficiencies. Although there are few living people with JIB, the management of
      these patients can be challenging. CASE PRESENTATION: We describe a case of a 58
      year-old female with a history of JIB 46 years prior who had an impending renal
      failure due to nephrolithiasis. She underwent a jejunostomy feeding tube prior to
      reversal. After reversal, our patient developed failure to thrive with functional
      obstruction of the newly incorporated small bowel. This bypassed bowel underwent
      a severe inflammatory transformation after the introduction of enteric feeds,
      suggesting an immunological type response to antigens in food. It wasn't until a
      long and debilitating 12 months and resection of this inflamed bowel that our
      patient was able to regain bowel function and gain weight. CONCLUSION:
      Jejunoileal bypass is an archaic procedure for morbid obesity. Due to its
      debilitating and at times lethal side effects, it has been replaced with newer
      techniques. Despite advances, there are still patients out there who have had a
      jejunoileal bypass. This case report and review of the literature details our
      experience with this procedure.

PMID- 30092541
TI  - Surgical approach to a mycotic aneurysm of the pulmonary artery presenting with
      hemoptysis - A case report and a review of the literature.
AB  - INTRODUCTION: Mycotic aneurysms of the pulmonary arteries are very rare and have
      high mortality. Risk groups are intravenous drug users and patients with
      congenital heart disorders. The surgical approach varies due to a limited number
      of reported cases. PRESENTATION OF CASE: We present a case of a mycotic aneurysm
      of the right pulmonary artery in a 56-year old man presenting with recurrent
      pneumonias, weight loss and hemoptysis. DISCUSSION: There is often a diagnostic
      delay because of non-specific symptoms mimicking more common disorders. Treatment
      strategies include conservative management, surgery and endovascular treatment.
      CONCLUSION: This report demonstrates a rare case of aneurysm of the pulmonary
      artery presenting with hemoptysis. For rapidly progressing proximal aneurysms of
      the pulmonary arteries, the midline surgical approach is recommended.

PMID- 30092542
TI  - Fast start-up of the cold-anammox process with different inoculums at low
      temperature (13  degrees C) in innovative reactor.
AB  - Three innovative reactors (CAMBR) through optimally combining with the Anaerobic
      Baffled reactor and Membrane bioreactor were applied to start up the cold-anammox
      process at low temperature (13  degrees C) through inoculating flocculent
      nitrification sludge (R1), anaerobic granular sludge (R2) and flocculent
      denitrification sludge (R3), respectively. Results showed that anammox process
      was started successfully with over 90% total nitrogen removal rate in R1, R2 and
      R3 after 75d, 45d, and 90d, respectively. Microbial community revealed that Ca.
      Brocadia and Ca. Jettenia were the dominant anammox bacteria in R1, R2 and R3,
      accounting for an abundance of 0.08%, 12.18%; 3.17%, 0 and 0.08%, 0.38%,
      respectively. Three anammox species, Ca. Brocadia caroliniensis, Ca. Brocadia
      sinica and Ca. Jettenia asiatica were annotated based on the phylogenetic tree,
      suggesting the anammox species with larger maximum growth rate contributed to the
      rapid start-up of the cold-anammox process. This study reinforces the potential
      application of mainstream anammox.

PMID- 30092543
TI  - NLRP3 inflammasome activation and lung fibrosis caused by airborne fine
      particulate matter.
AB  - Airborne fine particulate matter (PM2.5) has been known capable of causing lung
      inflammation and fibrosis, as a result of a series of chronic respiration
      diseases. Although NLRP3 inflammasome activation is essential for development of
      many chronic diseases, the relationship between PM2.5-induced toxicological
      effect and NLRP3 inflammasome activation is rarely investigated. Since PM2.5
      contains a large population of nanosized materials and many types of
      nanomaterials can activate NLRP3 inflammasome, the NLRP3 inflammasome activation
      and lung fibrosis induced by PM2.5 were investigated in the present study. PM2.5
      was found capable of causing weak cell death but potent IL-1beta secretion in THP
      1 cells, which was involved in NLRP3 inflammasome activation as evidenced by Z
      YVAD-FMK inhibited IL-1beta secretion and overexpressed ASC and NLRP3 protein in
      PM2.5 treated cells. PM2.5 could be internalized into cells through multiple
      endocytosis processes, such as phagocytosis and pinocytosis (macropinocytosis,
      clathrin- and caveolin-mediated endocytosis), and activate NLRP3 inflammasome
      through cathepsin B release, ROS production, and potassium efflux. After 21 days
      of exposure to PM2.5 through oropharyngeal aspiration, Balb/c mice showed
      increased IL-1beta and TGF-beta1 levels in the bronchoalveolar lavage fluid
      (BALF) of lung and significant collagen deposition around small airways of mice,
      suggesting potential lung inflammation and pulmonary fibrosis.

PMID- 30092544
TI  - Investigating Malaysian Nurses' perspectives of intercultural teaching in
      transnational higher education learning environments.
AB  - BACKGROUND: In recent years, many ASEAN countries, including Malaysia have
      embraced Transnational Higher Education (TNHE) post-registration top-up nursing
      degree programmes. These are bridging programmes that allow registered nurses to
      upgrade their diploma qualifications to a degree level. PURPOSE: To investigate
      the teaching and learning experiences of Malaysian nurses on Transnational Higher
      Education post-registration top-up degree programmes in Malaysia. DESIGN:
      Hermeneutic phenomenology and the ethnographic principle of cultural
      interpretation were used to explore the views of eighteen Malaysian nurses from
      two UK and one Australian TNHE universities (determined by convenience and
      snowball sampling methods) to ensure data saturation. Semi-structured interviews
      were conducted in English and Bahasa Malaysia (Malaysian language) to enable
      nurses' voices to define, describe and evaluate their TNHE classroom experiences.
      DATA ANALYSIS: Data were analysed using thematic analysis. FINDINGS: The nurses'
      experiences within the short one or 2 weeks TNHE intercultural teaching and
      learning environment identified four categories: language and teaching and
      learning issues; TNHE degree requirements, guidance and support; shock and coping
      strategies and acclimatisation. They suggest there was a conflict between the
      assumptions and expectations of the TNHE 'flying faculty' and nurses' about the
      programme of study. There were also mismatches between Western and Malaysian
      pedagogical preferences, guidance and support, and professional values.
      IMPLICATIONS FOR EDUCATION/PRACTICE: There is a need for TNHE 'flying faculty' to
      internationalise the theoretical knowledge to reduce cultural incongruities and
      dissimilarities. Cultural immersion will stimulate intercultural views and
      knowledge to equip nurses for promotional and/or global opportunities whilst
      enabling the 'flying faculty' to create new learning environments. The research
      provides insights to inform TNHE provider institutions to improve teaching and
      learning to enable nurses to make the theory-practice connection.

PMID- 30092546
TI  - Caring and curing: Considering the effects of hepatitis C pharmaceuticalisation
      in relation to non-clinical treatment outcomes.
AB  - BACKGROUND: The development of simplified and effective hepatitis C (HCV)
      pharmaceuticals enables treatment scale up among the most marginalised. This
      potentiates a promise of viral elimination at the population level but also
      individual level clinical and non-clinical benefits. Reports of transformative
      non-clinical outcomes, such as changes in self-worth and substance use, are
      primarily associated with arduous interferon-based treatments that necessitate
      intensive care relationships. We consider the implications of simplified
      treatment provision in the era of direct acting antivirals (DAAs) for the
      realisation of non-clinical benefits. METHODS: We draw on qualitative data from
      ethnographic observations and longitudinal interviews with people receiving (n =
      22) and providing (n = 10) HCV treatment in London during a transition in HCV
      biomedicine. First generation DAAs in conjunction with interferon were standard
      of care for most of this time, with the promise of simplified treatment provision
      on the horizon. FINDINGS: Patient accounts of care accentuate the transformative
      value of interferon-based HCV treatment derived through non-clinical benefits
      linked to identity and lifestyle change. Such care is constituted as extending
      beyond the virus and its biomedical effects, with nurse specialists positioned as
      vital to this care being realised. Provider accounts emphasise the increased
      pharmaceuticalisation of HCV treatment; whereby care shifts from the facilitation
      of therapeutic relationships to pharmaceutical access. CONCLUSION: HCV care in
      the interferon-era affords identity transformations for those receiving and
      providing treatment. Biomedical promise linked to the increasing
      pharmaceuticalisation of HCV treatment has disruptive potential, shifting how
      care is practised and potentially the realisation of non-clinical treatment
      outcomes.

PMID- 30092547
TI  - Medical marijuana laws and workplace fatalities in the United States.
AB  - AIMS: The aim of this research was to determine the association between
      legalizing medical marijuana and workplace fatalities. DESIGN: Repeated cross
      sectional data on workplace fatalities at the state-year level were analyzed
      using a multivariate Poisson regression. SETTING: To date, 29 states and the
      District of Columbia have legalized the use of marijuana for medicinal purposes.
      Although there is increasing concern that legalizing medical marijuana will make
      workplaces more dangerous, little is known about the relationship between medical
      marijuana laws (MMLs) and workplace fatalities. PARTICIPANTS: All 50 states and
      the District of Columbia for the period 1992-2015. MEASUREMENTS: Workplace
      fatalities by state and year were obtained from the Bureau of Labor Statistics.
      Regression models were adjusted for state demographics, the unemployment rate,
      state fixed effects, and year fixed effects. FINDINGS: Legalizing medical
      marijuana was associated with a 19.5% reduction in the expected number of
      workplace fatalities among workers aged 25-44 (incident rate ratio [IRR], 0.805;
      95% CI, .662-.979). The association between legalizing medical marijuana and
      workplace fatalities among workers aged 16-24, although negative, was not
      statistically significant at conventional levels. The association between
      legalizing medical marijuana and workplace fatalities among workers aged 25-44
      grew stronger over time. Five years after coming into effect, MMLs were
      associated with a 33.7% reduction in the expected number of workplace fatalities
      (IRR, 0.663; 95% CI, .482-.912). MMLs that listed pain as a qualifying condition
      or allowed collective cultivation were associated with larger reductions in
      fatalities among workers aged 25-44 than those that did not. CONCLUSIONS: The
      results provide evidence that legalizing medical marijuana improved workplace
      safety for workers aged 25-44. Further investigation is required to determine
      whether this result is attributable to reductions in the consumption of alcohol
      and other substances that impair cognitive function, memory, and motor skills.

PMID- 30092545
TI  - A computational method for longitudinal mapping of orientation-specific expansion
      of cortical surface in infants.
AB  - The cortical surface of the human brain expands dynamically and regionally
      heterogeneously during the first postnatal year. As all primary and secondary
      cortical folds as well as many tertiary cortical folds are well established at
      term birth, the cortical surface area expansion during this stage is largely
      driven by the increase of surface area in two orthogonal orientations in the
      tangent plane: 1) the expansion parallel to the folding orientation (i.e.,
      increasing the lengths of folds) and 2) the expansion perpendicular to the
      folding orientation (i.e., increasing the depths of folds). This information
      would help us better understand the mechanisms of cortical development and
      provide important insights into neurodevelopmental disorders, but still remains
      largely unknown due to lack of dedicated computational methods. To address this
      issue, we propose a novel method for longitudinal mapping of orientation-specific
      expansion of cortical surface area in these two orthogonal orientations during
      early infancy. First, to derive the two orientation fields perpendicular and
      parallel to cortical folds, we propose to adaptively and smoothly fuse the
      gradient field of sulcal depth and also the maximum principal direction field, by
      leveraging their region-specific reliability. Specifically, we formulate this
      task as a discrete labeling problem, in which each vertex is assigned to an
      orientation label, and solve it by graph cuts. Then, based on the computed
      longitudinal deformation of the cortical surface, we estimate the Jacobian matrix
      at each vertex by solving a least-squares problem and derive its corresponding
      stretch tensor. Finally, to obtain the orientation-specific cortical surface
      expansion, we project the stretch tensor into the two orthogonal orientations
      separately. We have applied the proposed method to 30 healthy infants, and for
      the first time we revealed the orientation-specific longitudinal cortical surface
      expansion maps during the first postnatal year.

PMID- 30092548
TI  - Winter road management effects on roadside soil and vegetation along a mountain
      pass in the Adirondack Park, New York, USA.
AB  - In 2003-2005, we resurveyed and expanded plots surveyed in 1985 to examine the
      cumulative impact of road salt (sodium chloride) and sand along a two-lane
      highway in the Adirondack State Park in New York State (USA). Annual salt
      applications in the period 1985-2005 ranged from 50 tonnes per centerline-km
      (1985) to 140 tonnes (2005) and sand applications ranged from nearly zero tonnes
      (2005) to 325 tonnes (1985). Roadside soils and vegetation were significantly
      impacted by salt deposition compared to soils and vegetation 30 m and 150 m from
      the road. Roadside soil contained more sand, less organic matter, had a lower
      cation exchange capacity, was denser, and retained less water than soils 30 m and
      150 m from the road. The concentration of sodium in roadside soils was elevated
      (103 vs. 44 ppm in soil 150 m from the roadside), and roadside concentrations of
      plant-nutritive cations were lower than 150 m from the road (roadside Mg, Ca and
      K concentrations were 0.2, 5, and 1 ppm respectively vs. 23,168, and 30 ppm at
      150 m from the road). Along the roadside, paper birch trees (Betula papyrifera)
      and other woody vegetation present in 1980 were absent in 2004, suggesting that
      survival and recruitment of paper birch trees was impacted by degradation of soil
      fertility, deposition of road salt and aerosolization of salt from the roadway.
      Roadside environmental degradation caused by winter road management has worsened
      since 1980; revegetation with native salt-tolerant plants may provide some
      mitigation of the most severe effects. Overall, we conclude that the full extent
      of roadside environmental degradation caused by winter road management can take
      decades to manifest, and this may be the case more generally along cold-climate
      montane roadways.

PMID- 30092549
TI  - Sulfonamides degradation assisted by UV, UV/H2O2 and UV/K2S2O8: Efficiency,
      mechanism and byproducts cytotoxicity.
AB  - The objective of this study was to analyze the effectiveness of UVC, UVC/H2O2 and
      UVC/K2S2O8 on the degradation of SAs. Rate constant values increased in the order
      SMZ < SDZ < SML and showed the higher photodegradation of sulfonamides with a
      penta-heterocycle. Quantum yields were 1.72 * 10-5 mol E-1, 3.02 * 10-5 mol E-1,
      and 6.32 * 10-5 mol E-1 for SMZ, SDZ and SML, respectively, at 60 min of
      treatment. R254 values show that the dose habitually utilized for water
      disinfection is inadequate to remove this type of antibiotic. The initial
      sulfonamide concentration has a major impact on the degradation rate. The
      degradation rates were higher at pH 12 for SMZ and SML. SMZ and SML
      photodegradation klambda values are higher in tap versus distilled water. The
      presence of radical promoters generates a greater increase in the degradation
      rate, UVC/K2S2O8 cost less energy, a mechanism was proposed, and the degradation
      by-products are less toxic than the original product.

PMID- 30092550
TI  - Methane hotspot localization and visualization at a large-scale Xi'an landfill in
      China: Effective tool for landfill gas management.
AB  - The variation characteristics and influence factors of methane emission at
      Jiangchungou landfill, one of the largest landfill in China, has been
      investigated by a one-year field monitoring campaign during 2015-2016. The
      methane concentration above the landfill surface varied widely from negligible to
      33,975 ppm. At least 75% of the methane concentration values of the sampling
      points are lower than the allowed limit (500 ppm). More than 95% of the high
      concentration zones (>500 ppm) were located in the temporary cover area (TA).
      Several environmental factors were found to be related to the variation of the
      concentration values. A clear correlation was observed between barometric
      pressure and exceeding-standard areas with a correlation coefficient of -0.743 (p
      < 0.1). The concentration values in the final cover area (FA) were about one
      order of magnitude lower than those observed in the TA due to the fact that rapid
      methane production rate happened in the first 180 days after the high kitchen
      content wastes were landfilled. The percentages of the measured concentration
      values exceeding 500 ppm near the gas collection wells in TA zone were 71.5% in
      November, 2015 and 55.7% in January, 2016 due to the leakage from the sides of
      gas collection wells. The average methane concentration values on the HDPE
      geomembrane was higher than those observed on the loess cover due to the fact
      that the geomembrane was relatively thin (0.5 mm) and can be easily damaged by
      the operation vehicles. Thicker geomembranes (>1.5 mm) with a good construction
      quality control are expected to provide better performance at this site.

PMID- 30092551
TI  - Optimization of co-culture inoculated microbial fuel cell performance using
      response surface methodology.
AB  - Microbial fuel cells (MFCs) are considered as promising technology to achieve
      simultaneous wastewater treatment and electricity generation. However,
      operational and technological developments are still required to make it as a
      sustainable technology. In the present study, response surface methodology (RSM)
      was used to evaluate the effects of substrate concentration, co-culture
      composition, pH and time on the performance of co-culture (Klebsiella variicola
      and Pseudomonas aeruginosa) inoculated double chamber MFC. From the statistical
      analysis, it can be seen that the performance of MFC was not influenced by the
      interaction between the initial COD and time, pH and time, pH and initial COD,
      time and initial COD. However, the interaction between the inoculum composition
      and time, pH and the inoculum composition, initial COD and inoculum composition
      significantly influenced the performance of MFC. Based on the RSM results, best
      performance (power density and COD removal efficiency) was obtained when the
      inoculum composition, initial COD, pH and time were about 1:1, 26.690 mg/L, 7.21
      and 15.50 days, respectively. The predictions from the model were in close
      agreement with the experimental results suggesting that the proposed model could
      adequately represent the actual relationships between the independent variables
      generating electricity and the COD removal efficiency.

PMID- 30092552
TI  - Crystal environment of impurity Nd3+ ion in yttrium and scandium orthosilicate
      crystals.
AB  - The ESEEM spectroscopy was used to determine positions of the 143Nd3+ impurity
      ions in Y2SiO5 single crystal. It is established that neodymium ions substitute
      yttrium ions in the Y2 positions with seven nearest oxygen ions. Crystal field
      parameters of 143Nd3+ impurity centers in isotopically pure Y228SiO5 and
      Sc228SiO5 single crystals were determined using data of CW EPR spectroscopy and
      the known energy level schemes.

PMID- 30092553
TI  - Global analysis of complex PELDOR time traces.
AB  - Pulsed electron-electron double resonance (PELDOR, alternatively called DEER for
      double electron-electron resonance) pulse sequences allow for the detection of
      echo decay curves that are modulated by dipole-dipole-coupling frequencies of
      interacting electron spins. With increasing distance between them, the echo decay
      needs to be monitored over a progressively extended time period. However, since
      the echo intensity typically falls off exponentially with increasing time, this
      might be problematic with respect to the minimum signal-to-noise ratio required
      for a sound data analysis. In this contribution we present the new PELDOR
      analysis tool GloPel (Global analysis of PELDOR data), an open-source Python
      based application, that allows to extract improved-quality distance distributions
      from PELDOR data for which no ideal signal-to-noise ratio can be achieved for a
      very long observation window. By using Tikhonov regularization, GloPel allows for
      the simultaneous analysis of two time traces acquired for a sample in two
      different observation time windows, thus taking advantage of both, the typically
      high signal-to-noise ratio of the time trace acquired at early times of the echo
      decay, and the best possible background function fitted for the decay at later
      times, which is in most cases superimposed with considerable noise. In this way,
      short distances are not overseen in the higher noise of the longer time traces
      while long distances are not artificially shortened by limiting the observation
      time window of the experiment. Following our suggested data acquisition
      procedure, a significant reduction of the measurement time may also be achieved.

PMID- 30092554
TI  - 99mTc labelled complexes with secnidazole xanthate: Synthesis and evaluation as
      potential radiotracers to target tumor hypoxia.
AB  - In this study, the commercially available secnidazole was successfully converted
      to secnidazole xanthate (SNXT), in which the xanthate group can act as a
      bifunctional chelator to coordinate with 99mTc. 99mTc-nitrido complex of
      SNXT(99mTcN-SNXT) and 99mTc-oxo complex of SNXT(99mTcO-SNXT) were prepared with
      high radiochemical purity. Both of the complexes were found to be stable in vitro
      and to exhibit similar hydrophilicity. In addition, comparative in vitro cell
      uptake studies under anoxic and normoxic conditions demonstrated that both agents
      were preferentially taken up by hypoxic cells. Biodistribution studies in mice
      bearing S180 tumor showed 99mTcO-SNXT exhibited a higher tumor uptake and tumor
      to-muscle ratio than 99mTcN-SNXT. Furthermore, in SPECT imaging study, 99mTcO
      SNXT exhibited a clear accumulation in tumor at 2 h post-injection, suggesting
      its potential to be a novel hypoxia imaging agent.

PMID- 30092555
TI  - Everolimus-based combination therapies for HR+, HER2- metastatic breast cancer.
AB  - Metastatic breast cancer (MBC) is the leading cause of cancer-related morbidity
      and mortality among women worldwide. Endocrine therapy is the standard of care
      for the most common subtype of MBC, hormone-receptor positive (HR+), human
      epidermal growth factor receptor 2-negative (HER2-) disease. Advances in treating
      this type of MBC have focused on improving the efficacy of endocrine therapy by
      adding agents that target specific molecular pathways of breast cancer cell
      growth and survival. The combination of the aromatase inhibitor exemestane and
      the mammalian target of rapamycin inhibitor, everolimus, more than doubled median
      progression-free survival compared with exemestane alone (7.8 vs 3.2 months,
      respectively; hazard ratio 0.45 [95% confidence interval 0.38-0.54]; log rank P <
      0.0001) in the BOLERO-2 study in postmenopausal women with HR+, HER2- locally
      advanced or metastatic breast cancer that had recurred or progressed on prior non
      steroidal aromatase inhibitor therapy. In addition, everolimus plus exemestane
      was associated with a manageable safety profile. The results of BOLERO-2 led to
      regulatory approval of everolimus plus exemestane. Additional everolimus-based
      combinations have been or are under investigation in the HR+, HER2- MBC setting,
      including combinations with letrozole, fulvestrant, ribociclib, tamoxifen, and
      chemotherapy. This review summarizes key data on everolimus-based combinations
      focusing on efficacy, safety, biomarkers, quality of life, and health economic
      outcomes. These data are discussed in the context of the changing MBC treatment
      algorithm to provide insights into the clinical relevance of everolimus-based
      combinations.

PMID- 30092557
TI  - Von Willebrand factor and the aortic valve: Concepts that are important in the
      transcatheter aortic valve replacement era.
AB  - Since the approval of the first transcatheter aortic valve replacement (TAVR)
      device in 2011, this technology has undergone substantial enhancements and
      exponential growth. However, valve thrombosis and residual paravalvular leaks
      (PVL) are among the challenges that require further investigation. Recently,
      monitoring von Willebrand factor (vWF) multimers has emerged as a tool to help
      evaluate the severity of PVL after TAVR. Following TAVR, vWF large multimers
      recovery have been documented. The role of large vWF multimers recovery and their
      interactions with platelets, and the endothelium have not been entirely
      elucidated. In this review, we discuss vWF synthesis and its role in aortic
      stenosis. We further provide an overview of the studies that investigated changes
      affecting vWF multimers following TAVR and the role of HMW vWF multimers
      monitoring in the determination of PVL severity. We also offer potential future
      directions for what will be fertile ground for research in this field.

PMID- 30092556
TI  - Photoperiod during maternal pregnancy and lifetime depression in offspring.
AB  - Experimental studies indicate that perinatal light exposure has enduring effects
      on affective behaviors in rodents; however, insufficient research has explored
      this hypothesis in humans. We examined photoperiod (i.e., day length) metrics
      during maternal pregnancy in relation to lifetime depression in the longitudinal
      Nurses' Health Study (NHS) and NHS II. 160,723 participants reported birth date
      and birth state (used to derive daily photoperiod based on published mathematical
      equations), and clinician-diagnosed depression and antidepressant use throughout
      adulthood. Logistic regression was used to estimate odds ratios (OR) (and 95%
      confidence intervals [CI]) for depression (defined as clinician diagnosis and
      antidepressant use) across quintiles of two exposures during maternal pregnancy:
      1) total photoperiod (total number of daylight hours) and 2) differences between
      minimum/maximum photoperiod; each trimester of pregnancy was examined separately.
      Total photoperiod during maternal pregnancy was not associated with depression
      overall or by trimester of pregnancy. However, larger differences between
      minimum/maximum photoperiod during maternal pregnancy were related to lower odds
      of depression (multivariable [MV]-adjusted OR: 0.86, 95% CI: 0.83, 0.90 comparing
      extreme quintiles of exposure; p-trend<0.0001); this association appeared
      specific to the second trimester of pregnancy (MV-adjusted p-trends = 0.03,
      <0.0001, and 0.3 across the three trimesters, respectively). In addition, birth
      at higher latitude (where larger differences in minimum/maximum photoperiod
      exist) was associated with a significant reduction in the lifetime risk of
      depression. These findings are consistent with an emerging hypothesis in which
      perinatal light exposure may influence risk of depression, and they might be
      understood through the conceptual framework of adaptive developmental plasticity.

PMID- 30092558
TI  - Characterization of anthocyanin and proanthocyanidin biosynthesis in two
      strawberry genotypes during fruit development in response to different light
      qualities.
AB  - LED-based light sources that can provide narrowly-centered spectrum have been
      frequently applied to manipulate the plant growth, development and metabolism in
      recent years. This study aimed to find out the effect of different light
      qualities on the production of anthocyanins and proanthocyanidins. The results
      showed RL (red light), BL (blue light), RBL (red light: blue light = 1:1) induced
      the strawberry fruit coloration earlier by increasing the content of total
      anthocyanins as a result of high expression of related genes, which was also
      concluded from a*, C*, h degrees  values in 'Tokun' at 28 DAF, and RBL
      significantly promoted anthocyanin and proanthocyanidin biosynthesis in these two
      strawberry genotypes during fruit development. Simultaneously, the contents of
      anthocyanins and proanthocyanidins in 'Toyonaka' were also remarkably upregulated
      by BL and RL, respectively, indicating different strawberry genotypes to some
      extent probably had a distinct response to light quality. Hence, genotype factor
      should be taken into consideration when supplement of light quality was used as
      practical application in strawberry cultivation. Taken together, this study
      provided an insight into a further understanding of roles of light quality in the
      color formation for strawberry and a potential means to increase the health
      related values of strawberry through altering the anthocyanin and
      proanthocyanidin contents of the fruit.

PMID- 30092559
TI  - Comparison of integrated sustainable biodiesel and antibacterial nano silver
      production by microalgal and yeast isolates.
AB  - Microalgal isolates (Chlorella sp. and Spirulina sp.) and yeast isolates (Candida
      albicans and Saccharomyces sp.) were employed as the resources of biodiesel
      production and silver nanoparticle synthesis. The prominent peaks of the FTIR
      spectrum accustomed the efficient lipid property. The developed profile
      containing fatty acid methyl ester (FAME) displayed the elevated amount of both
      saturated (C15:0, C17:0, C21:0) and unsaturated (C17:1, C18:2, C20:4) fatty
      acids. The physicochemical properties analyzed by using Biodiesel analyzer
      V1.1.software, confirmed the competency of the isolates for sustainable biodiesel
      production. Biosynthesis of silvernanoparticles (AgNPs) were accomplished
      extracellularly by using supernatant of microalgal and yeast culture. The maximum
      absorbance at 420 and 421 nm under UV-visible spectra showed the presence of
      nanoparticles. The purity of the synthesized AgNPs were analyzed by XRD analysis.
      The elemental silver presence was affirmed by EDAX, SEM and AFM, the results
      revealed spherical crystalline shaped nanoparticles of size ranging from 2.0 to
      7.3 nm. The antimicrobial efficacy of the silver nanoparticles (AgNPs) against
      various clinical pathogens which includes Bacillus sp., E. coli, Klebsiella sp.,
      Proteus sp. and Staphylococcus aureus were observed. However, enhanced
      antimicrobial activity was displayed by the AgNPs, produced by Candida albicans
      (12 mm) against Bacillus sp., and E.coli, the nanoparticle produced by Chlorella
      sp. showed the least antagonistic activity (07 mm).

PMID- 30092560
TI  - Analysis of storage compounds and inorganic ions in dimorphic seeds of
      euhalophyte Suaeda salsa.
AB  - Suaeda salsa is an annual euhalophytic herb that produces dimorphic seeds, such
      as small black seeds and big brown seeds. In the present study, the fatty acid
      composition, content of total phenols, flavonoids, carotenoid and inorganic ions
      in dimorphic seeds of the species collected in the field were measured. There was
      no significant difference in total oil content between black and brown seeds.
      Seed total oil content was approximately 19% based on dry weight. The most
      abundant fatty acid was linoleic acid, and the content was 76.3 and 70.5% of
      total fatty acids in black and brown seeds, respectively. Furthermore, the
      contents of total phenols, flavonoids, carotenoids and inorganic ions in brown
      seeds were higher than those in black seeds, which might be the mechanism of
      higher salt tolerance of brown seeds than black seeds. The ecological,
      physiological and genetic mechanisms of the different abilities of nutrition
      accumulation in black and brown seeds of S. salsa are also discussed and worthy
      to be investigated in the future.

PMID- 30092561
TI  - Evaluation of Sustained-Release Steroid Hydrogels in a Guinea Pig Model for Noise
      Induced Hearing Loss.
AB  - The otoprotective effects of thermoreversible poloxamer 407 hydrogels containing
      dexamethasone or triamcinolone acetonide were evaluated in an animal model of
      noise-induced hearing loss. Seven days after noise exposure, hearing threshold
      shifts at 16 kHz were significantly reduced in the 6% dexamethasone group (p <
      0.05). Even though no significant differences in hair cell counts were found,
      histological analysis revealed a significantly higher spiral ganglion cell
      density in the first turn of the cochlea in this group (p < 0.05). No
      otoprotective effects were observed after the application of the triamcinolone
      acetonide hydrogels. As the findings of this study indicate potential
      otoprotective effects of sustained topical dexamethasone delivery in the setting
      of noise-induced hearing loss, this strategy merits further evaluation.

PMID- 30092562
TI  - Factors Associated with Stroke Misdiagnosis in the Emergency Department: A
      Retrospective Case-Control Study.
AB  - BACKGROUND: Failure to recognise acute stroke may result in worse outcomes due to
      missed opportunity for acute stroke therapies. Our study examines factors
      associated with stroke misdiagnosis in patients admitted to a large comprehensive
      stroke centre. METHODS: Retrospective review comparing 156 consecutive stroke
      patients misdiagnosed in emergency department (ED) with 156 randomly selected
      stroke controls matched for age, gender, language spoken and stroke subtype for
      the period 2014-2016. RESULTS: There were 141 ischemic and 15 hemorrhagic
      misdiagnosed strokes (median age: 77 years, male:female = 1.3: 1). Symptom
      resolution, altered mental status, nausea/vomiting, dizziness and vertigo favored
      misdiagnosis (p < 0.05). Hemiparesis and dysarthria favored an accurate diagnosis
      (p < 0.05). Misdiagnosed patients were more commonly triaged into a lower ED
      category (62 vs. 42%, p = 0.001), clinically assessed as Face, Arm, Speech and
      Time (FAST) - negative (78 vs. 22%, p < 0.001) and underwent delayed CT imaging
      (median 4.1 vs. 1.5 h, p < 0.001). Misdiagnosed patients were more likely to have
      posterior circulation stroke (PCS; 39 vs. 22%, p = 0.01) and be admitted under
      non-neurological services (35 vs. 11%, p < 0.001) with worse discharge outcomes
      including increased mortality. CONCLUSIONS: Patients with stroke misdiagnosis
      were commonly FAST-negative with nonspecific symptoms including altered mental
      status, dizziness and nausea/vomiting often associated with PCS. Improved
      diagnostic accuracy may increase access to acute therapies.

PMID- 30092565
TI  - Xenopus: An Undervalued Model Organism to Study and Model Human Genetic Disease.
AB  - The function of normal and defective candidate genes for human genetic diseases,
      which are rapidly being identified in large numbers by human geneticists and the
      biomedical community at large, will be best studied in relevant and predictive
      model organisms that allow high-speed verification, analysis of underlying
      developmental, cellular and molecular mechanisms, and establishment of disease
      models to test therapeutic options. We describe and discuss the pros and cons of
      the frog Xenopus, which has been extensively used to uncover developmental
      mechanisms in the past, but which is being underutilized as a biomedical model.
      We argue that Xenopus complements the more commonly used mouse and zebrafish as a
      time- and cost-efficient animal model to study human disease alleles and
      mechanisms.

PMID- 30092564
TI  - The Head Turning Sign in Dementia and Mild Cognitive Impairment: Its Relationship
      to Cognition, Behavior, and Cerebrospinal Fluid Biomarkers.
AB  - BACKGROUND/AIMS: The head turning sign (HTS) is frequently noticed in clinical
      practice, but few studies have investigated its etiological and
      neuropsychological correlates. METHODS: The presence and frequency of the HTS was
      operationalized and prospectively evaluated in patients with Alzheimer's disease
      (AD), amnestic mild cognitive impairment (MCI), and behavioral-variant
      frontotemporal dementia (bvFTD). Cerebrospinal fluid (CSF) samples for AD
      biomarkers were collected. Mini-Mental State Examination, Montreal Cognitive
      Assessment, Geriatric Depression Scale (GDS), and insight scale scores were
      ascertained. RESULTS: A total of 84 patients were included. The HTS was more
      prevalent in AD than in MCI or bvFTD. It correlated negatively with cognitive
      measures and depression. It also had a positive correlation with CSF total tau
      and hyperphosphorylated tau proteins. Total tau protein and GDS score were the
      only variables independently associated with the HTS. CONCLUSIONS: The presence
      of the HTS in a cognitively impaired individual suggests a diagnosis of AD. A
      higher HTS frequency correlates with higher CSF total tau levels, a smaller GDS
      score, and worse cognitive measures. In the MCI subgroup, the HTS may suggest a
      higher risk of progression.

PMID- 30092563
TI  - WBP2 Downregulation Inhibits Proliferation by Blocking YAP Transcription and the
      EGFR/PI3K/Akt Signaling Pathway in Triple Negative Breast Cancer.
AB  - BACKGROUND/AIMS: Dysregulated expression of WW domain-binding protein 2 (WBP2) is
      associated with poor prognosis in ER+ breast cancer patients. However, its role
      in triple negative breast cancer (TNBC) has not been previously assessed.
      Therefore, we aimed to elucidate the functional mechanism of WBP2 in TNBC cells.
      METHODS: qRT-PCR, western blotting, and immunohistochemical staining were used to
      evaluate WBP2 expression in TNBC patient tumors and cell lines. HCC1937 and MDA
      MB-231 cells transiently transfected with WBP2 small interfering RNA (siRNA), miR
      613 mimics, or miR-613 inhibitors were subject to assays for cell viability,
      apoptosis and cell cycle distribution. Co-immunoprecipitation, western blotting
      or qRT-PCR were employed to monitor changes in signaling pathway-related genes
      and proteins. Luciferase assays were performed to assess whether WBP2 is a direct
      target of miR-613. The effect of miR-613 on tumor growth was assessed in vivo
      using mouse xenograft models. RESULTS: The expression of WBP2 was upregulated in
      TNBC tissues and cells. Expression of WBP2 was significantly correlated with Ki67
      in TNBC patients. Knockdown of WBP2 inhibited cellular proliferation, promoted
      apoptosis, and induced cell cycle arrest of TNBC cells. miR-613 directly bound to
      the 3'-untranslated region (3'-UTR) of WBP2 and regulated the expression of WBP2.
      Moreover, miR-613 reduced the expression of WBP2 and suppressed tumor growth of
      TNBC cells in vivo. Knockdown of WBP2 inhibited YAP transcription and the
      EGFR/PI3K/Akt signaling pathway in TNBC cells, and these effects were reversed by
      inhibition of miR-613. CONCLUSION: WBP2 overexpression is associated with the
      poor prognosis of TNBC patients and the miR-613-WBP2 axis represses TNBC cell
      growth by inactivating YAP-mediated gene expression and the EGFR/PI3K/Akt
      signaling pathway.

PMID- 30092566
TI  - Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile
      Dysfunction Induced by a High-Fat Diet.
AB  - BACKGROUND/AIMS: Consumption of a high-fat (HF) diet exacerbates metabolic
      cardiomyopathy through lipotoxic mechanisms. In this study, we explored the role
      of aldehyde dehydrogenase-2 (ALDH2) in myocardial damage induced by a HF diet.
      METHODS: Wild-type C57 BL/6J mice were fed a HF diet or control diet for 16
      weeks. ALDH2 overexpression was achieved by injecting a lentiviral ALDH2
      expression vector into the left ventricle. RESULTS: Consumption of a HF diet
      induced metabolic syndrome and myocardial remodeling, and these deleterious
      effects were attenuated by ALDH2 overexpression. In addition, ALDH2
      overexpression attenuated the cellular apoptosis and insulin resistance
      associated with a HF diet. Mechanistically, ALDH2 overexpression inhibited the
      expression of c-Jun N-terminal kinase (JNK)-1, activated protein 1 (AP-1),
      insulin receptor substrate 1 (IRS-1), 4- hydroxynonenal, caspase 3, transforming
      growth factor beta1, and collagen I and III, and enhanced Akt phosphorylation.
      CONCLUSION: ALDH2 may effectively attenuate myocardial remodeling and contractile
      defects induced by a HF diet through the regulation of the JNK/AP-1 and IRS-1/Akt
      signaling pathways. Our study demonstrates that ALDH2 plays an essential role in
      protecting cardiac function from lipotoxic cardiomyopathy.

PMID- 30092567
TI  - Eight Items to Check on a Temporal Bone CT-Scan.
AB  - Imaging data provided by computed tomography scans of the temporal bone are
      fundamental for both the diagnosis and treatment of diseases affecting this
      complex structure. Despite its importance, the expertise required to analyze this
      exam is seldom properly acquired as it is time-consuming and often neglected
      among young doctors and even otolaryngologists. Physicians may not even have a
      look at the scans but rely only on radiology reports. Radiologists, on the other
      hand, may not describe the individual scans the same way as clinicians. Lack of a
      standardized and didactic protocol for scrolling through the images obtained
      might also contribute to the difficulties reported by residents and physicians in
      daily practice. We present here a sequential checklist which could be employed in
      a systematic and organized manner, aiming to both develop and practice the know
      how of this indispensable and challenging method of evaluation of the temporal
      bone.

PMID- 30092569
TI  - High Dietary omega-6:omega-3 PUFA Ratio Is Positively Associated with Excessive
      Adiposity and Waist Circumference.
AB  - OBJECTIVE: The aim of this study was to analyze dietary omega-6:omega-3
      polyunsaturated fatty acid (PUFA) ratio and its association with adiposity and
      serum adiponectin levels in a Mexican population. METHODS: In this cross
      sectional study, individuals with a BMI >= 18.5 kg/m2, were classified using four
      methods to measure adiposity. Parameters of body composition were measured by
      InBody 3.0. Diet intake was evaluated prospectively using a 3-day written food
      record. Serum high-molecular weight adiponectin isoform was measured using an
      ELISA assay. Biochemical and adiposity variables were analyzed by tertiles of
      dietary omega-6:omega-3 PUFA ratio. RESULTS: A total of 170 subjects were
      recruited with a mean age of 36.9 +/- 11.8 years. The 73.5% of subjects were
      women. Subjects in the higher tertile of dietary omega-6:omega-3 PUFA ratio had
      more adiposity and higher levels of triglycerides, VLDL-c, glucose, insulin and
      HOMA-IR than those in the first tertile (p < 0.05). Adiponectin levels showed a
      trend according to dietary omega-6:omega-3 PUFA ratio (p = 0.06). A linear
      regression model showed that waist circumference, insulin, and HOMA-IR have
      positive associations with dietary omega-6:omega-3 PUFA ratio. CONCLUSION: This
      study suggests that high dietary omega-6:omega-3 PUFA ratio is positively
      associated with excessive adiposity and worse metabolic profile.

PMID- 30092570
TI  - Rapid Growth and Early Metastasis of Papillary Thyroid Carcinoma in an Adolescent
      Girl with Graves' Disease.
AB  - BACKGROUND: The risk factors for rapid growth and early metastasis of papillary
      thyroid carcinoma (PTC) and the role of coexisting Graves' disease in the
      clinical course of PTC remain uncertain in children. CASE DESCRIPTION: We report
      on a Japanese girl, whose PTC rapidly grew and metastasized within 4 years.
      Graves' disease was diagnosed by the presence of serum TSH receptor antibodies at
      8 years of age when thyroid ultrasonography detected no nodules. After 4 years of
      effective treatment with thiamazole, multifocal nodules - up to 47 mm in diameter
      - were detected on thyroid ultrasonography. Chest CT scan revealed multiple
      metastatic lesions in the lung. After total thyroidectomy, PTC was pathologically
      diagnosed. The patient underwent two courses of radioactive iodine (RAI)
      treatment, but the pulmonary metastatic lesions did not take up the RAI.
      Molecular analyses of the PTC tissue identified a TFG/NTRK1 chimeric gene and
      disclosed the preserved expression of TSHR and the reduced expression of SLC5A5
      compared with non-tumor thyroid tissue. CONCLUSIONS: Rapid growth and early
      metastasis of PTC with coexisting Graves' disease in this patient can be related
      to a combination of multiple factors including preserved TSHR expression, reduced
      SLC5A5 expression, and TFG/NTRK1 rearrangement.

PMID- 30092568
TI  - Roles of Exosome-Like Vesicles Released from Inflammatory C2C12 Myotubes:
      Regulation of Myocyte Differentiation and Myokine Expression.
AB  - BACKGROUND/AIMS: The complicated differentiation processes of cells in skeletal
      muscle against inflammation that induce muscle atrophy are not fully elucidated.
      Given that skeletal muscle is a secretory organ, we evaluated the effects of
      inflammation on myogenic signals and myokine expression, and the roles of
      inflammatory exosomes released by myotubes in myogenic differentiation. METHODS:
      Inflammation was induced by treatment of fully differentiated C2C12 myotubes with
      a cytokine mixture of TNF-alpha and INF-gamma. Exosome-like vesicles (ELVs) were
      isolated from conditioned media of control or inflamed myotubes and incubated
      with myoblasts. The expression of molecular switches that contribute to myogenic
      differentiation, including several kinases, their downstream targets, and
      myokines, were evaluated using immunoblot analysis in inflamed myotubes and in
      myoblasts treated with ELVs. RESULTS: Inflammation activated molecular mechanisms
      contributing to muscle atrophy, including AMPK, p-38 MAPK and JNK, while
      inhibiting Akt-mediated myogenic signals. In addition, inflammation induced
      myostatin expression with suppression of a myostatin-counteracting myokine,
      decorin. Well-characterized ELVs released from inflamed myotubes induced myoblast
      inflammation and inhibited myogenic mechanisms while stimulating atrophic
      signals. CONCLUSION: Inflammation of skeletal muscle induces muscle atrophy via
      multiple mechanisms, including the regulation of myokines and kinases.
      Inflammatory ELVs are likely to contribute to inflammation-induced muscle
      atrophy.

PMID- 30092571
TI  - Genome-Wide Analysis of Prognostic lncRNAs, miRNAs, and mRNAs Forming a Competing
      Endogenous RNA Network in Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is the most prevalent subtype of
      primary liver tumor worldwide. Growing evidence has led to a consensus that long
      non-coding RNAs (lncRNAs) have considerable influence on tumorigenesis and tumor
      progression of HCC via the mechanism of competing endogenous RNAs (ceRNAs).
      METHODS: Here, we systematically investigated the expression landscape and
      clinical prognostic value of lncRNAs, micorRNAs (miRNAs), and mRNAs from The
      Cancer Genome Atlas. Differentially expressed RNAs were submitted to Cox
      regression analysis and the construction of prognostic indexes. A lncRNA-miRNA
      mRNA regulatory network was then constructed based on interaction information
      derived from miRcode, TargetScan, miRTarBase, and miRDB. Gene Ontology and Kyoto
      Encyclopedia of Genes and Genomes analyses were performed to reveal and determine
      the functional roles of the ceRNA network in the prognosis of HCC. RESULTS: We
      detected 77 differentially expressed lncRNAs, 29 differentially expressed miRNAs,
      and 1014 differentially expressed mRNAs in HCC, which were significantly
      associated with the overall survival of patients with HCC. We developed three
      prognostic prediction models that showed moderate predicting prognosis
      performance and were highly correlated with tumor burden, histological grade and
      pathological stage. Additionally, 10 survival-related lncRNAs, 6 survival-related
      miRNAs, and 31 survival-related mRNAs were included to develop a ceRNA network.
      Further functional enrichment analysis suggested that the ceRNA network was
      associated with a dismal prognosis for patients with HCC by disturbing the
      homeostasis of the cell cycle. CONCLUSION: Together, our study highlights the
      significant roles of lncRNAs in the development and implementation of monitoring
      surveillance and prognosis of HCC and provides a deeper understanding of the
      lncRNA-related ceRNA regulatory mechanism in the pathogenesis of HCC.

PMID- 30092572
TI  - Triplet Chemotherapy (FOLFOXIRI) Plus Bevacizumab Versus Doublet Chemotherapy
      (FOLFOX/FOLFIRI) Plus Bevacizumab in Conversion Therapy for Metastatic Colorectal
      Cancer: a Meta-Analysis.
AB  - BACKGROUND/AIMS: Conversion therapy can convert unresectable metastatic
      colorectal cancer (mCRC) into resectable. However, the optimal conversion regimen
      was not yet defined. This meta-analysis aimed to compare the efficacy and safety
      of the triplet chemotherapy (FOLFOXIRI) plus bevacizumab (Bev) with doublet
      chemotherapy (FOLFOX/FOLFIRI) plus Bev in conversion therapy. METHODS: Randomized
      controlled trials (RCTs) from databases, including Pubmed, EMBASE, Cochrane
      clinical trials, clinicaltrial.gov and some conferences, were searched from the
      inception to November 2017. The R0 resection, objective response rate (ORR),
      progression-free survival (PFS), overall survival (OS) and the incidence of
      adverse events were pooled with the use of hazard ratio (HR) or risk ratio (RR).
      RESULTS: Four RCTs with 1013 patients were included. FOLFOXIRI plus Bev regimen
      significantly improved the overall R0 resection rate (RR 1.41, 95% confidence
      interval (CI) 1.07-1.85, I2=37%), liver R0 resection rate (RR 2.28, 95% CI 1.34
      3.89, I2=0%), ORR (RR 1.20, 95% CI 1.09-1.32, I2=0%), PFS (HR 0.72, 95% CI 0.62
      0.84, I2=36%) and OS (HR 0.80, 95% CI 0.66-0.97, I2=0%). There was no significant
      difference in any Grade>=3 adverse event (RR 1.08, 95% CI 0.99-1.17, I2=0%)
      between two regimens. FOLFOXIRI-Bev was associated with a higher risk of
      neutropenia (RR 1.77, 95% CI 1.13-2.79, I2=68%) and diarrhea (RR 1.65, 95% CI
      1.17-2.32, I2=0%). CONCLUSIONS: Triplet chemotherapy plus Bev significantly
      improved the R0 resection rates, ORR, PFS and OS in comparison with doublet
      chemotherapy plus Bev in conversion therapy for mCRC patients, with a higher risk
      of neutropenia and diarrhea.

PMID- 30092573
TI  - Estimation of the Prevalence of Amyotrophic Lateral Sclerosis in the United
      States Using National Administrative Healthcare Data from 2002 to 2004 and
      Capture-Recapture Methodology.
AB  - BACKGROUND: National administrative healthcare data may be used as a case-finding
      method for prevalence studies of chronic disease in the United States, but the
      completeness of ascertainment likely varies depending on the disease under study.
      METHODS: We used 3 case-finding sources (Medicare, Medicaid, and Veterans
      Administration data) to estimate the prevalence of amyotrophic lateral sclerosis
      (ALS) in the United States for 2002-2004, and applied the capture-recapture
      methodology to estimate the degree of under-ascertainment when relying solely on
      these sources for case identification. RESULTS: Case-finding completeness was 76%
      overall and did not vary by race, but was lower for males (77%) than for females
      (88%), and lower for patients under age 65 (66%) than patients over age 65 (79%).
      The uncorrected ALS prevalence ratio was 2.8/100,000 in 2002, 3.3/100,000 in
      2003, and 3.7/100,000 in 2004. After correcting for under-ascertainment, the
      annual prevalence increased by approximately 1 per 100,000 to 3.7/100,000 in 2002
      (95% CI 3.66-3.80), 4.4/100,000 in 2003 (95% CI 4.34-4.50), and 4.8/100,000 in
      2004 (95% CI 4.76-4.91). CONCLUSIONS: Federal healthcare claims databases
      ascertained are a very efficient method for identifying the majority of ALS
      prevalent cases in the National ALS Registry, and may be enhanced by having
      patients self-register through the registry web portal.

PMID- 30092574
TI  - Extradural Spinal Hamartoma Causing Spinal Cord Compression in an Adolescent
      Male: An Extremely Rare Case and Review of the Literature.
AB  - Spinal hamartoma is an extremely rare, benign spinal lesion occurring in
      children. It may cause spinal cord compression and subsequent neurological
      deficits. On reviewing the literature, of a total of 20 cases, only 2 cases are
      reported in an adolescent age group. It may be a pure spinal hamartoma, or
      sometimes it may be associated with either neurofibromatosis type I or spinal
      dysraphism. MRI is the investigation of choice. Surgical excision of the lesion
      and the decompression of the cord are the definitive treatment. Here, we pre-sent
      a similar case in a 16-year-old adolescent male, its diagnosis and further
      management.

PMID- 30092575
TI  - Post-Prandial Hyperinsulinaemic Hypoglycaemia after Oesophageal Surgery in
      Children.
AB  - INTRODUCTION: Post-prandial hyperinsulinaemic hypoglycaemia (PPHH) is a
      recognized complication of various gastric surgeries in children, but rarely
      reported after oesophageal atresia repair. We report 2 children diagnosed with
      PPHH after oesophageal surgery and the challenges of their management. Case 1: A
      2-year-old boy diagnosed with oesophageal atresia at birth was surgically
      repaired requiring 6 oesophageal dilatations in the first year of life. At 11
      months of age, he manifested hypoglycaemic seizures and investigations confirmed
      PPHH. Acarbose and diazoxide trials failed. He was managed with 17-h continuous
      gastrostomy feeds. Currently, he is 28 months old with euglycaemia on daytime
      bolus gastrostomy feeds and overnight 12-h continuous gastrostomy feeds. Case 2:
      A 6-month-old girl diagnosed with Wolf-Hirschhorn syndrome and tracheo
      oesophageal fistula was surgically repaired, requiring monthly oesophageal
      dilatations. At 5 months of age, she was reported to have hypoglycaemia and PPHH
      was confirmed. She responded to diazoxide and continuous nasogastric tube feeds,
      but developed pulmonary hypertension pos-sibly diazoxide-induced. Subsequently,
      diazoxide was stopped and normoglycaemia was secured via 20-h continuous
      gastrostomy feeds. CONCLUSION: PPHH may be an underdiagnosed complication in
      children undergoing surgery for oesophageal atresia. These children must be
      monitored closely for symptoms of hypoglycaemia and if there are concerns must be
      screened for possible PPHH. Our cases demonstrate that continuous feeding
      regimens might be the only therapeutic option, until PPHH gradually lessens in
      intensity over time.

PMID- 30092576
TI  - Characterization of Recombinant Adeno-Associated Viral Transduction and Safety
      Profiles in Cardiomyocytes.
AB  - BACKGROUND/AIMS: Cardiovascular diseases (CVD) are the leading causes for human
      mortality. However, the effective treatment for these diseases are still lacking.
      Currently, gene therapy could be a potential way for efficiently treating heart
      diseases. The aim of our study is to analyze the transduction efficacy and safety
      profile of recombinant adeno associated virus (AAV) serotype 9 for cardiomyocytes
      in vivo and in vitro. METHODS: We produced rAAV serotype 9 expressing enhanced
      green fluorescence protein (EGFP) driven by a cardiac troponin T (cTNT) promoter,
      and characterized its transduction efficiency in primary cultured cardiomyocytes
      in vitro, and in wild-type mouse heart tissue in vivo. RESULTS: Our data showed
      that rAAV9 efficiently transduced mouse cardiomyocytes in vitro. Following
      intravenous injection, rAAV9 could efficiently and safely transduce
      cardiomyocytes that are involved in heart diseases. CONCLUSION: Our findings
      suggested that rAAV9 can efficiently and safely transduce cardiomyocytes in vitro
      and/or in vivo. The rAAV9 serotype vector could constitute a powerful toolbox for
      future gene therapy of heart diseases.

PMID- 30092577
TI  - Mechanisms of Action of Kefir in Chronic Cardiovascular and Metabolic Diseases.
AB  - The gut microbiota maintains a complex mutual interaction with different organs
      of the host. Whereas in normal conditions this natural community of trillions of
      microorganisms greatly contributes to the human health, gut dysbiosis is related
      with onset or worsening of diverse chronic systemic diseases. Thus, the
      reestablishment of gut microbiota homeostasis with consumption of prebiotics and
      probiotics may be a relevant strategy to prevent or attenuate several
      cardiovascular and metabolic complications. Among these functional foods, the
      synbiotic kefir, which is a fermented milk composed of a mixture of bacteria and
      yeasts, is currently the most used and has attracted the attention of health care
      professionals. The present review is focused on reports describing the
      feasibility of kefir consumption to provide benefits in cardiometabolic diseases,
      including hypertension, vascular endothelial dysfunction, dyslipidemia and
      insulin resistance. Interestingly, recent studies show that mechanisms of actions
      of kefir in cardiometabolic diseases include recruitment of endothelial
      progenitor cells, improvement of the balance vagal/sympathetic nervous system,
      diminution of excessive generation of reactive oxygen species, angiotensin
      converting enzyme inhibition, anti-inflammatory cytokines profile and alteration
      of the intestinal microbiota. These findings provide a better understanding about
      the mechanisms of the beneficial actions of kefir and motivate further
      investigations to determine whether the use of this synbiotic could also be
      translated into clinical improvements in cardiometabolic diseases.

PMID- 30092578
TI  - lncRNA TUG1-Mediated Mir-142-3p Downregulation Contributes to Metastasis and the
      Epithelial-to-Mesenchymal Transition of Hepatocellular Carcinoma by Targeting
      ZEB1.
AB  - BACKGROUND/AIMS: MicroRNA-142-3p (miR-142-3p) is dysregulated in many
      malignancies and may function as a tumor suppressor or oncogene in tumorigenesis
      and tumor development. However, few studies have investigated the clinical
      significance and biological function of miR-142-3p in hepatocellular carcinoma
      (HCC). METHODS: The expression levels of taurine upregulated gene 1 (TUG1), miR
      142-3p, and zinc finger E-box-binding homeobox 1 (ZEB1) were evaluated in HCC
      tissues and cell lines by quantitative real-time PCR. MTT and colony formation
      assays were used to detect cell proliferation ability, transwell assays were used
      to assess cell migration and invasion, and luciferase reporter assays were used
      to examine the interaction between the long noncoding RNA TUG1 and miR-142-3p.
      Tumor formation was evaluated through in vivo experiments. RESULTS: miR-142-3p
      was significantly downregulated in HCC tissues, but TUG1 was upregulated in HCC
      tissues. Knockdown of TUG1 and upregulation of miR-142-3p inhibited cell
      proliferation, cell migration, cell invasion, and the epithelial-mesenchymal
      transition (EMT). miR-142-3p was found to be a prognostic factor of HCC, and the
      mechanism by which TUG1 upregulated ZEB1 was via direct binding to miR-142-3p. In
      vivo assays showed that TUG1 knockdown suppressed cell proliferation and the EMT
      in nude mice. CONCLUSION: The results of this study suggest that the TUG1/miR-142
      3p/ ZEB1 axis contributes to the formation of malignant behaviors in HCC.

PMID- 30092579
TI  - Sex Differences in the Prevalence of and Risk Factors for Nonvascular Cognitive
      Function in Rural, Low-Income Elderly in Tianjin, China.
AB  - BACKGROUND: At the global level, dementia is the leading cause of dependence and
      disability among the elderly. Although the preponderant prevalence in women has
      been identified, the sex differences in risk factors were unclear. We aimed to
      evaluate the sex differences in the prevalence of nonvascular cognitive
      impairment and the risk factors among the elderly in rural China screened with
      the Mini-Mental State Examination (MMSE). METHODS: Between 2014 and 2015, a
      population-based cross-section study was conducted to collect basic information
      among the elderly aged 60 years and over. Those participants with the previous
      history of stroke or heart disease were excluded in this study. Nonvascular
      cognitive impairment was assessed using the MMSE scores. RESULTS: The prevalence
      of cognitive impairment was 32.4% overall, 25.6% in men and 38.1% in women. In
      the multivariate analysis, older age and lower education were risk factors both
      in men and in women; older, large waist circumference was a protective factor for
      cognitive function in men; higher blood pressure was the risk factor in women.
      CONCLUSION: These findings suggest that it is crucial to manage and control
      hypertension and improve educational attainment in order to reduce the prevalence
      and burden of nonvascular cognitive impairment among low-income residents, both
      men and women, in rural China.

PMID- 30092580
TI  - Order of Treatment Matters in Ischemic Stroke: Mechanical Thrombectomy First,
      Then Carotid Artery Stenting for Tandem Lesions of the Anterior Circulation.
AB  - BACKGROUND: One endovascular treatment option of acute ischemic stroke due to
      tandem occlusion (TO) comprises intracranial thrombectomy and acute extracranial
      carotid artery stenting (CAS). In this setting, the order of treatment may impact
      the clinical outcome in this stroke subtype. METHODS: Retrospective analysis was
      performed on data prospectively collected in 4 international stroke centers
      between 2013 and 2017. One hundred sixty-five patients with anterior TO were
      treated by endovascular therapy. Clinical and procedural data were evaluated.
      Favorable clinical outcome was defined as modified Rankin Scale (mRS) <=2 at 90
      days. Propensity score matching was performed for different treatment strategies.
      RESULTS: Patients' mean age was 65 +/- 11 years and 118 were male (69%). The
      median admission National Institutes of Health Stroke Scale was 15 (interquartile
      range 8). In 59% of the patients (n = 101), the antegrade strategy (first
      stenting, then thrombectomy) was -performed, in 41% (n = 70) retrograde treatment
      (first thrombectomy, then stenting). Successful reperfusion (mTICI >=2b) was
      achieved in 128 patients (75%). Fifty-nine patients (39%) showed a favorable
      clinical outcome after 90 days. After propensity score matching, data of 100
      patients could be analyzed. Analysis revealed that the retrograde strategy
      yielded a significantly higher rate of successful reperfusion compared to the
      antegrade strategy (92 vs. 56%; p < 0.001). The rate of favorable clinical
      outcome after 90 days (mRS <=2) was consistently higher (44 vs. 30%; p < 0.05) in
      the retrograde strategy group. CONCLUSION: Mechanical thrombectomy prior to acute
      CAS in TO is a predictive factor for favorable clinical outcome at 90 days.

PMID- 30092582
TI  - Administration of Thyrotropin-Releasing Hormone in the Hypothalamic
      Paraventricular Nucleus of Male Rats Mimics the Metabolic Cold Defense Response.
AB  - BACKGROUND: Cold exposure increases thyrotropin-releasing hormone (TRH)
      expression primarily in the hypothalamic paraventricular nucleus (PVN). The PVN
      is a well-known hypothalamic hub in the control of energy metabolism. TRH
      terminals and receptors are found on PVN neurons. We hypothesized that TRH
      release in the PVN plays an important role in the control of thermogenesis and
      energy mobilization during cold exposure. METHODS: Male Wistar rats were exposed
      to a cold environment (4 degrees C) or TRH retrodialysis in the PVN for 2 h. We
      compared the effects of cold exposure and TRH administration in the PVN on plasma
      glucose, corticosterone, and thyroid hormone concentrations, body temperature,
      locomotor activity, as well as metabolic gene expression in the liver and brown
      adipose tissue. RESULTS: Cold exposure increased body temperature, locomotor
      activity, and plasma corticosterone concentrations, but blood glucose
      concentrations were similar to that of room temperature control animals. TRH
      administration in the PVN also promptly increased body temperature, locomotor
      activity and plasma corticosterone concentrations. However, TRH administration in
      the PVN markedly increased blood glucose concentrations and endogenous glucose
      production (EGP) compared to saline controls. Selective hepatic sympathetic or
      parasympathetic denervation reduced the TRH-induced increase in glucose
      concentrations and EGP. Gene expression data indicated increased gluconeogenesis
      in liver and lipolysis in brown adipose tissue, both after cold exposure and TRH
      administration. CONCLUSIONS: We conclude that TRH administration in the rat PVN
      largely mimics the metabolic and behavioral changes induced by cold exposure
      indicating a potential link between TRH release in the PVN and cold defense.

PMID- 30092583
TI  - Delayed Intravenous Thrombolysis in Patients with Minor Stroke.
AB  - BACKGROUND: The actions and responses of the hospital personnel during acute
      stroke care in the emergency department (ED) may differ according to the severity
      of a patient's stroke symptoms. We investigated whether the time from arrival at
      ED to various care steps differed between patients with minor and non-minor
      stroke who were treated with intravenous tissue plasminogen activator (IV tPA).
      METHODS: We included consecutive patients who received IV tPA during a 1.5 year
      period in 5 hospitals. Minor stroke was defined as a National Institutes of
      Health Stroke Scale (NIHSS) score < 5. We compared various intervals from arrival
      at the ED to treatment between patients with minor stroke and those with non
      minor stroke (NIHSS score >=5). Delayed treatment was defined as a door-to-needle
      time > 40 min. RESULTS: During the study period, 356 patients received IV tPA
      treatment. The median door-to-needle time was significantly longer in the minor
      stroke group than it was in the non-minor stroke group (43 min [interquartile
      range [IQR] 35.5-55.5] vs. 37 min [IQR 30-46], p < 0.001). The minor stroke group
      had a significantly longer door-to-notification time (7 min [IQR 4.5-12] vs. 5
      min [IQR 3-8], p < 0.001) and door-to-imaging time (20 min [IQR 15-26.5] vs. 16
      min [IQR 11-21], p < 0.001) than did the non-minor stroke group. However, the
      imaging-to-needle time was not different between the groups. Multivariable
      analyses revealed that minor stroke was associated with delayed treatment (OR
      2.54 [95% CI 1.52-4.30], p = 0.001). CONCLUSIONS: Our findings show that the door
      to-needle time was longer in patients with minor stroke than it was in those with
      non-minor stroke, mainly owing to delayed action in the initial steps of
      neurology notification and imaging. Our findings suggest that some quality
      improvement initiatives are necessary for patients with suspected stroke with
      minor symptoms.

PMID- 30092581
TI  - A Point Prevalence Study of Delirium in Italian Nursing Homes.
AB  - BACKGROUND: Delirium is a common geriatric syndrome. Few studies have been
      conducted in nursing home (NH) residents. The aim of this project was to perform
      a point prevalence study of delirium in Italian NHs. METHODS: Data collected in
      71 NHs are presented. Inclusion criteria were age >=65 years and native Italian
      speaker. Exclusion criteria were coma, aphasia, and end-of-life status.
      Sociodemographic and medical data were recorded. Delirium was assessed using the
      Assessment Test for Delirium and Cognitive Impairment (4-AT). Patients with a 4
      AT score >=4 were considered to have delirium. Motor subtype was evaluated using
      the Delirium Motor Subtype Scale (DMSS). RESULTS: A total of 1,454 patients were
      evaluated (mean age 84.4 +/- 7.4 years, 70.2% female), of whom 535 (36.8%) had
      delirium. In multivariate logistic regression analysis, variables significantly
      associated with delirium were education (OR 0.94, 95% CI 0.91-0.97), dementia (OR
      3.12, 95% CI 2.38-4.09), functional dependence (OR 6.13, 95% CI 3.08-12.19 for
      ADL score 0; OR 1.99, 95% CI 1.03-3.84 for ADL score 1-5), malnutrition (OR 4.87,
      95% CI 2.68-8.84), antipsychotics (OR 2.40, 95% CI 1.81-3.18), and physical
      restraints (OR 2.48, 95% CI 1.71-3.59). CONCLUSION: Delirium is common in older
      NH residents. Simple assessment tools might facilitate its recognition in this
      vulnerable population.

PMID- 30092584
TI  - Evidence for Seasonal Variation of Bell's Palsy in Germany.

PMID- 30092585
TI  - Cognitive Therapy for Dementia Patients: A Systematic Review.
AB  - BACKGROUND: Cognitive therapy is a well-established intervention for treating
      elderly suffering from dementia. In particular, reality orientation and skills
      training seem to be effective interventions for reversing cognitive impairment
      among elderly, although findings are inconclusive. Therefore, a systematic update
      of the existing evidence of cognitive therapy for people suffering from dementia
      is needed. AIM: To review existing scientific evidence regarding the efficacy of
      cognitive therapies for elderly suffering from dementia. METHODS: Studies were
      retrieved from several bibliographic databases (January 2009 to December 2017)
      with prespecified selection criteria, data extraction, and methodological quality
      assessment. RESULTS: In total, 10 reality orientation, 25 skills training, and 12
      mixed trials were identified as meeting the inclusion criteria and were
      systematically reviewed. Results from reality orientation trials showed minor
      effects for cognitive assessments, while skills training trials and mixed trials
      showed contradicting effects on cognition. Effects on other outcomes (e.g., daily
      functioning, depression, language) were limited or not found. CONCLUSIONS: Skills
      training trials and mixed trials seem to affect cognitive impairment in a
      positive way, although the results are inconclusive. Comparison between studies
      was difficult due to differences in form of intervention. Because findings are
      inconclusive, more structuralized and comparable randomized controlled trials are
      needed.

PMID- 30092586
TI  - Protective Effects of Hydrogen Sulfide Against Cigarette Smoke Exposure-Induced
      Placental Oxidative Damage by Alleviating Redox Imbalance via Nrf2 Pathway in
      Rats.
AB  - BACKGROUND/AIMS: Cigarette smoke exposure (CSE) during pregnancy is a well
      recognized health hazard that causes placental damage. Hydrogen sulfide (H2S) has
      been reported to protect multiple organs from injury. However, the protective
      effects of H2S have not been tested in the placenta. This study aimed to explore
      the potential of H2S in protecting placenta against oxidative injury induced by
      CSE during pregnancy and the possible underlying mechanisms. METHODS: Pregnant SD
      rats were randomly divided into 4 groups: NaCl, NaHS (a donor of H2S), CSE and
      CSE+NaHS. Placental oxidative damage was detected by 8-hydroxy-2-deoxyguanosine
      (8-OHdG) stain and malondialdehyde (MDA) assay. Placental redox status was
      assessed by measuring reactive oxygen species (ROS), total antioxidant capacity
      (T-AOC) and glutathione (GSH) levels, as well as copper/zinc SOD (SOD1),
      manganese SOD (SOD2), catalase (CAT) and glutathione peroxidase (GPx) activities
      and expressions. Meanwhile, nuclear factor erythroid 2-related factor 2 (Nrf2)
      was analyzed by immunohistochemistry, real-time PCR and Western blot. RESULTS: We
      found that NaHS markedly reduced the elevated levels of 8-OHdG and MDA induced by
      CSE. Further, NaHS treatment effectively mitigated CSE-induced placental redox
      imbalance by inhibiting ROS production, restoring T-AOC level, increasing
      GSH/GSSG ratio, and augmenting SOD1 SOD2, CAT and GPx activities and expressions.
      More notably, NaHS administration also reversed the aberrant decrease of Nrf2 due
      to CSE in rat placentas. CONCLUSION: Our data demonstrate that H2S can protect
      against CSE-induced placental oxidative damage probably by alleviating redox
      imbalance via Nrf2 pathway.

PMID- 30092588
TI  - The Risk of Second Primary Colorectal Adenocarcinomas Is Not Increased among
      Patients with Gastroenteropancreatic Neuroendocrine Neoplasms: A Nationwide
      Population-Based Study.
AB  - BACKGROUND: Second primary colorectal adenocarcinomas (SPCA) may occur with a
      higher frequency in patients with gastroenteropancreatic neuroendocrine neoplasms
      (GEP-NENs). In a nationwide population-based study, we investigated the risk of
      SPCA in GEP-NEN patients and compared it to the general population. METHODS:
      Using the nationwide Danish registries, we identified 2,831 GEP-NEN patients
      (median age 63 years [IQR 50-73 years], 53% women) diagnosed in 1995-2010. We
      used Cox regression to compare the incidence of SPCA in GEP-NEN patients relative
      to a gender- and age-matched general population sample of 56,044 persons.
      RESULTS: We observed 20 SPCAs among the 2,831 GEP-NEN patients with a total time
      at risk of 14,003 years (incidence = 143 per 100,000 person-years) and 770
      colorectal adenocarcinomas in the general population of 56,044 persons with a
      total time at risk of 466,801 years (incidence = 165 per 100,000 person-years).
      The hazard ratio (HR) of SPCA from GEP-NEN diagnosis to the end of follow-up was
      1.22 (95% CI: 0.78-1.92) in GEP-NEN patients compared to the general population.
      This nonsignificant association was the result of a strong positive association
      in the first 6 months after diagnosis of GEP-NEN (HR = 9.43 [95% CI: 4.98-17.86])
      followed by a negative association in the remainder of the follow-up period (HR =
      0.50 [95% CI: 0.20-1.21]). CONCLUSION: In this population-based study, there was
      no increased risk of SPCA among GEP-NEN patients. The clinical workup in newly
      diagnosed GEP-NEN patients likely explains the positive short-term association
      followed by a negative association.

PMID- 30092589
TI  - Thyroid Hormone Receptor Alpha Deletion in ApoE-/- Mice Alters the Arterial Renin
      Angiotensin System and Vascular Smooth Muscular Cell Cholesterol Metabolism.
AB  - Thyroid hormone (TH) regulates gene transcription by binding to TH receptors
      (TRs). TRs regulate the genes of lipid metabolism and the renin-angiotensin
      system (RAS). We examined the effect of TRalpha deletion in ApoE-/- mice (DKO
      mice) on the following: (i) the expression of genes controlling cholesterol
      metabolism and tissue (t)RAS in the liver and aorta and (ii) the expression of
      these genes and the regulation of cholesterol content in cultured vascular smooth
      muscle cells (VSMCs). TRalpha deletion in ApoE-/- mice led to the repression of
      genes involved in the synthesis and influx of cholesterol in the liver. However,
      TRalpha deletion in the arterial wall suppressed the expression of genes involved
      in the esterification and excretion of cholesterol and enhanced the expression of
      angiotensinogen (AGT). The VSMCs of the ApoE-/- and DKO mice increased their
      cholesterol content during cholesterol loading, but failed to increase the
      expression of ATP-binding cassette transporter A1 (ABCA1). T3 addition partially
      corrected these abnormalities in the cells of the ApoE-/- mice but not those of
      the DKO mice. In conclusion, TRalpha deletion in ApoE-/- mice slightly increases
      the expression of tRAS in the aorta and aggravates the dysregulation of
      cholesterol content in the VSMCs.

PMID- 30092587
TI  - Serum Vitamin D Concentrations and Cognitive Change Over 20 Years: The
      Atherosclerosis Risk in Communities Neurocognitive Study.
AB  - BACKGROUND/AIMS: 25-hydroxyvitamin D (25[OH]D) concentrations have been
      associated with cognitive decline and incident dementia in elderly populations;
      however, these relationships are susceptible to reverse causation. Less is known
      about the association of midlife 25(OH)D with long-term cognitive decline.
      METHODS: This was a prospective cohort study of 13,044 participants (mean age 57
      years at baseline) in the Atherosclerosis Risk in Communities Study. 25(OH)D was
      measured from serum collected at baseline (1990-1992) using liquid chromatography
      tandem high-sensitivity mass spectrometry. Cognition was assessed using 3
      neuropsychological tests at 3 time points, which were combined into a composite
      cognitive Z-score. Multivariable-adjusted linear mixed-effects models with random
      intercepts and slopes were used to estimate associations between 25(OH)D and
      cognitive change over 20 years. RESULTS: Compared to persons with sufficient
      25(OH)D (>=30 ng/mL), those with deficient (< 20 ng/mL) and intermediate (20-< 30
      ng/mL) 25(OH)D concentrations had similar cognitive decline in composite
      cognitive Z-scores (deficient versus sufficient: -0.035 [95% CI -0.104 to 0.033]
      and intermediate versus sufficient: -0.029 [95% CI -0.080 to 0.023]).
      CONCLUSIONS: Lower concentrations of 25(OH)D measured in midlife were not
      significantly associated with more rapid cognitive decline over a 20-year follow
      up period. The results of this prospective study are less susceptible to reverse
      causation than prior studies.

PMID- 30092590
TI  - Allogenic Natural Killer Cell Immunotherapy Combined with Irreversible
      Electroporation for Stage IV Hepatocellular Carcinoma: Survival Outcome.
AB  - BACKGROUND/AIMS: We evaluated the clinical effectiveness of irreversible
      electroporation (IRE) in combination with immunotherapy using allogenic natural
      killer cells (NK) for stage IV hepatocellular carcinoma (HCC). METHODS: The study
      involved 40 patients with stage IV HCC who were divided equally into two groups:
      1) simple IRE; and 2) IRE plus allogenic NK cells (IRE-NK); we mainly assessed
      the overall survival (OS). RESULTS: The effect of the IRE-NK treatment was
      synergistic, i.e., not only did it enhance immune function, it also decreased
      alpha-fetoprotein expression and showed significantly good clinical
      effectiveness. At the median 7.6-month follow-up (range, 3.8-12.1 months), median
      OS was higher in the IRE-NK group (10.1 months) than in the IRE group (8.9
      months, P = 0.0078). CONCLUSION: IRE combined with allogeneic NK cell
      immunotherapy significantly increases the median OS of patients with stage IV
      HCC.

PMID- 30092591
TI  - Bioactive Peptide Improves Diet-Induced Hepatic Fat Deposition and Hepatocyte
      Proinflammatory Response in SAMP8 Ageing Mice.
AB  - BACKGROUND/AIMS: High-fat diet (HFD)-induced nonalcoholic fatty liver disease
      (NAFLD) poses therapeutic challenges in elderly subjects. Due to lack of
      efficient drug therapy, plant-based bioactive peptides have been studied as
      alternative strategy in NAFLD and for less toxicity in elderly. To mimic fatty
      liver in aging conditions, researchers highly commended the genetically
      engineered strains SAMP8 (senescence-accelerated mice prone 8). However, there is
      a paucity of reports about the anti-steatosis effects of bioactive peptides
      against fatty liver development under a combined action of high-fat diet exposure
      and aging process. This study was conducted to evaluate the activity of
      DIKTNKPVIF peptide synthesized from alcalase-generated potato protein hydrolysate
      (PH), on reducing HFD-driven and steatosis-associated proinflammatory reaction in
      ageing model. METHODS: Five groups of six-month-old SAMP8 mice (n=4, each) were
      fed either a normal chow (NC group) for 14 weeks upon sacrifice, or induced with
      a 6-week HFD feeding, then treated without (HCO group) or with an 8-week
      simultaneous administration of peptide (HPEP group), protein (HPH group) or
      probucol (HRX group). Liver organs were harvested from each group for
      histological analysis and immunoblot assay. RESULTS: In contrast to NC, extensive
      fat accumulation was visualized in the liver slides of HCO. Following the trends
      of orally administered PH, intraperitoneally injected peptide reduces hepatic fat
      deposition and causes at protein level, a significant decrease in HFD-induced
      proinflammatory mediators p-p38 MAPK, FGF-2, TNF-alpha, IL-6 with concomitant
      reactivation of AMPK. However, p-Foxo1 and PPAR-alpha levels were slightly
      changed. CONCLUSION: Oral supplementation of PH and intraperitoneal injection of
      derived bioactive peptide alleviate proinflammatory reaction associated with
      hepatosteatosis development in elderly subjects, through activation of AMPK.

PMID- 30092593
TI  - Correlation between Serum Squamous Cell Carcinoma Antigen Level and Tumor Volume
      in Head and Neck Cancer.
AB  - PURPOSE OF STUDY: An association of squamous cell carcinoma antigen (SCC-Ag)
      level with cancer prognosis has been reported in many studies. Our investigators
      conducted the first study determining a correlation between the SCC-Ag level and
      the tumor volume in head and neck cancer. PROCEDURES: The SCC-Ag level of
      patients were measured from the serum, whilst the tumor volume was calculated by
      the ellipsoid formula and verified by logistic software on radiology. The
      correlation between SCC-Ag level and tumor volume was analyzed. RESULTS: Fifty
      two patients were studied, with the mean age of 62.4 years. Tumor types were:
      oral cavity cancer (11 cases, 21.6%), oropharyngeal cancer (21 cases, 40.38%),
      hypopharyngeal cancer (8 cases, 15.7%), and laryngeal cancer (12 cases, 23.5%).
      Mean tumor volume was 20.01 mL (range 0.02-91.46 mL). Mean SCC-Ag level was 2.69
      ng/mL (range 0.5-14.6 ng/mL). The critical point of SCC-Ag was 5.8 ng/mL. The
      Pearson's correlation coefficient between SCC-Ag level and tumor volume was 0.524
      (p = 0.0002). CONCLUSIONS: SCC-Ag moderately correlates with tumor volume in head
      and neck cancer patients, with statistical significance. We suggest that using
      tumor volume, rather than a one-dimensional measurement such as tumor size, to
      analyze correlation with SCC-Ag offers a more accurate means of cancer prognosis.

PMID- 30092592
TI  - Identification of Potential Prognostic Long Non-Coding RNA Biomarkers for
      Predicting Survival in Patients with Hepatocellular Carcinoma.
AB  - BACKGROUND/AIMS: The aim of the current study was to identify potential
      prognostic long non-coding RNA (lncRNA) biomarkers for predicting survival in
      patients with hepatocellular carcinoma (HCC) using The Cancer Genome Atlas (TCGA)
      dataset and bioinformatics analysis. METHODS: RNA sequencing and clinical data of
      HCC patients from TCGA were used for prognostic association assessment by
      univariate Cox analysis. A prognostic signature was built using stepwise
      multivariable Cox analysis, and a comprehensive analysis was performed to
      evaluate its prognostic value. The prognostic signature was further evaluated by
      functional assessment and bioinformatics analysis. RESULTS: Thirteen
      differentially expressed lncRNAs (DELs) were identified and used to construct a
      single prognostic signature. Patients with high risk scores showed a
      significantly increased risk of death (adjusted P < 0.0001, adjusted hazard ratio
      = 3.522, 95% confidence interval = 2.307-5.376). In the time-dependent receiver
      operating characteristic analysis, the prognostic signature performed well for
      HCC survival prediction with an area under curve of 0.809, 0.782 and 0.79 for 1-,
      3- and 5-year survival, respectively. Comprehensive survival analysis of the 13
      DEL prognostic signature suggested that it serves as an independent factor in
      HCC, showing a better performance for prognosis prediction than traditional
      clinical indicators. Functional assessment and bioinformatics analysis suggested
      that the prognostic signature was associated with the cell cycle and peroxisome
      proliferator-activated receptor signaling pathway. CONCLUSIONS: The novel lncRNA
      expression signature identified in the present study may be a potential biomarker
      for predicting the prognosis of HCC patients.

PMID- 30092594
TI  - Analysis of Circulating Tumor Cells in Ovarian Cancer and Their Clinical Value as
      a Biomarker.
AB  - BACKGROUND/AIMS: Monitoring the appearance and progression of tumors are
      important for improving the survival rate of patients with ovarian cancer. This
      study aims to examine circulating tumor cells (CTCs) in epithelial ovarian cancer
      (EOC) patients to evaluate their clinical significance in comparison to the
      existing biomarker CA125. METHODS: Immuomagnetic bead screening, targeting
      epithelial antigens on ovarian cancer cells, combined with multiplex reverse
      transcriptase-polymerase chain reaction (Multiplex RT-PCR) was used to detect
      CTCs in 211 samples of peripheral blood (5 ml) from 109 EOC patients. CTCs and
      CA125 were measured in serial from 153 blood and 153 serum samples from 51
      patients and correlations with treatment were analyzed. Immunohistochemistry was
      used to detect the expression of tumor-associated proteins in tumor tissues and
      compared with gene expression in CTCs from patients. RESULTS: CTCs were detected
      in 90% (98/109) of newly diagnosed patients. In newly diagnosed patients, the
      number of CTCs was correlated with stage (p=0.034). Patients with stage IA-IB
      disease had a CTC positive rate of 93% (13/14), much higher than the CA125
      positive rate of only 64% (9/14) for the same patients. The numbers of CTCs
      changed with treatment, and the expression of EpCAM (p=0.003) and HER2 (p=0.035)
      in CTCs was correlated with resistance to chemotherapy. Expression of EpCAM in
      CTCs before treatment was also correlated with overall survival (OS) (p=0.041).
      CONCLUSION: Detection of CTCs allows early diagnose and expression of EpCAM in
      CTC positive patients predicts prognosis and should be helpful for monitoring
      treatment.

PMID- 30092595
TI  - Impact of CYP2C19 Polymorphism on Antiplatelet Potency of Prasugrel 5 and 10 mg
      Daily Maintenance.
AB  - BACKGROUND: Whether genetic polymorphisms (GP) impact residual platelet
      aggregation (RPA) following prasugrel is unclear, especially during maintenance
      phase. We assessed the influence of CYP2C19 GP carriers on RPA in the prospective
      observational cohort study. METHODS AND RESULTS: All post-stent patients (n =
      206) received prasugrel 60 mg loading and either 5 or 10 mg daily maintenance
      with aspirin100 mg. RPA levels by light transmission aggregometry (LTA),
      multiplate electrode aggregometry (MEA), and VerifyNow (P2Y12 reaction units,
      PRU) with CYP2C19 GP were measured simultaneously. Demographics and clinical
      characteristics were not useful for predicting response after prasugrel. GP
      carriers exhibited higher RPA (PRU: p = 0.001, LTA: p = 0.001, MEA: p = 0.023)
      than noncarriers. CYP2C19 carriers had higher RPA for 5 mg (n = 35; LTA: p =
      0.043, MEA: p = 0.023) and reached significance for 10 mg (n = 27; LTA: p =
      0.001, PRU: p = 0.001) prasugrel. When divided into extensive, intermediate, and
      poor metabolizers, all exhibited statistical differences among the 3 groups (LTA:
      14.9 +/- 12.3%, 22.6 +/- 14.9%, 22.9 +/- 15.6%, p = 0.002; PRU: 104.1 +/- 70.8%,
      141.8 +/- 78.0%, 151.0 +/- 84.8%, p = 0.003; MEA: 19.7 +/- 8.9%, 24.4 +/- 12.2%,
      28.1 +/- 14.7%, p = 0.002). CONCLUSION: CYP2C19 GP impacts RPA during maintenance
      phase prasugrel in Korean outpatients. This effect is consistent for both of the
      approved prasugrel doses potentially affecting long-term outcomes including
      bleeding risks. However, the clinical utility of these findings is still
      uncertain, and requires more evidence from larger randomized trials beyond East
      Asians.

PMID- 30092596
TI  - Large-Scale in Vitro Transcription, RNA Purification and Chemical Probing
      Analysis.
AB  - BACKGROUND/AIMS: RNA elements such as catalytic RNA, riboswitch, microRNA, and
      long non coding RNA (lncRNA) play central roles in many cellular processes.
      Studying diverse RNA functions require large quantities of RNA for precise
      structure analysis. Current RNA structure and function studies can benefit from
      improved RNA quantity and quality, simpler separation procedure and enhanced
      accuracy of structural analysis. METHODS: Here we present an optimized protocol
      for analyzing the structure of any RNA, including in vitro transcription, size
      exclusion chromatography (SEC) based denaturing purification and improved
      secondary structure analysis by chemical probing. RESULTS: We observed that
      higher Mg2+, nucleoside triphosphate (NTP) concentrations and longer reaction
      duration can improve the RNA yield from in vitro transcription, specifically for
      longer and more complicated constructs. Our improved SEC-based denaturing RNA
      purification effectively halved the experiment duration and labor without
      introducing any contaminant. Finally, this study increased the accuracy and
      signal-to-noise ratio (SNR) of selective 2'-hydroxyl acylation analyzed by primer
      extension (SHAPE) chemical probing for analyzing RNA structure. CONCLUSION: Part
      or all of our modified method can improve almost any RNA-related study from
      protein-RNA interaction analysis to crystallography.

PMID- 30092597
TI  - Utility of Horizontal Sections of Scalp Biopsies in Differentiating between
      Androgenetic Alopecia and Alopecia Areata.
AB  - BACKGROUND: Androgenetic alopecia (AGA) and alopecia areata (AA) are common
      causes of alopecia which can sometimes be difficult to differentiate clinically.
      Horizontal sections of scalp biopsies are used to study non-cicatricial alopecias
      due to the ability to perform both quantitative and morphometric analysis of hair
      follicles on them. METHODS: It was a prospective, cross-sectional study conducted
      to assess the utility of horizontal sections to differentiate between the
      alopecias. Fifty-two cases were included: 20 cases of male AGA, 11 of female AGA
      and 21 cases of AA. After clinical examination and dermoscopy, a skin biopsy was
      taken and subjected to transverse sectioning. Histopathological assessment was
      done by two dermatopathologists blinded to clinical details. RESULTS: Among the
      quantitative parameters, terminal:vellus hair ratio (3.08 in AGA and 1.83 in AA,
      p = 0.0091) and anagen:non-anagen hair ratio (9.25 in AGA and 3.56 in AA, p =
      0.0021) were significantly lower in AA. In qualitative parameters, peribulbar
      inflammation was seen in 63% of AA cases (p = 0.0001). Pigment casts were seen in
      twice the number of AA (57%) than AGA (26%) cases. Broad avascular stelae and
      focal trichomalacia were seen in 9.5% of AA cases. CONCLUSION: Besides peribulbar
      inflammation, we found a lower anagen:non-anagen hair ratio and presence of
      pigment casts in transverse sections of scalp biopsies favouring AA over AGA.

PMID- 30092599
TI  - Surgical Treatment of Cardiac Metastases: Analysis of a 13-Year Single-Center
      Experience.
AB  - BACKGROUND:  Cardiac metastases are more common than primary malignant tumors of
      the heart and are usually treated surgically as a palliative approach. In this
      study, we reviewed our experience with the surgical treatment of patients with
      cardiac metastases of various types of malignant tumors. METHODS:  Between 2003
      and 2016, 10 patients underwent surgery for cardiac metastases at our
      institution. RESULTS:  The mean age was 53.5 +/- 19 years. Female patients made
      up 60% (n = 6) of the collective. The cohort included cardiac metastases of
      diverse origins (peripheral sarcomas, melanoma, rectal carcinoma, and
      hepatocellular carcinoma). The left side of the heart was more frequently
      affected (n = 7). In only six patients, the primary malignancy was known at the
      time of cardiac surgery. The interval between the first diagnosis of the primary
      tumor and cardiac metastases ranged from simultaneous diagnosis to up to 19
      years. At the time of the diagnosis of the cardiac metastases, seven patients
      already had multiple metastases: all seven patients had pulmonary metastases, and
      three of them additionally had hepatic, cerebral, or osseous metastases. Only
      four patients were symptomatic (atrial fibrillation, pericardial effusion,
      tachycardia with chest pain, dyspnea). There was no in-hospital death. The
      postoperative course was uneventful overall. The one- and two-year survival rates
      were similar, that is, 76%. The median follow-up time was 5.4 years. CONCLUSIONS:
      Surgical intervention for treating cardiac metastases is associated with
      uneventful clinical outcome and acceptable survival in this critically ill
      population. Control of the primary malignancy, and maybe other metastases,
      determines the survival.

PMID- 30092598
TI  - Endoplasmic Reticulum Stress Affects Lipid Metabolism in Atherosclerosis Via CHOP
      Activation and Over-Expression of miR-33.
AB  - BACKGROUND/AIMS: Endoplasmic reticulum (ER) stress is an important event in
      atherosclerosis. Recent studies have shown that ER stress deregulates cholesterol
      metabolism via multiple pathways. This study aimed to determine the relationship
      between ER stress and lipid metabolism and to verify that upregulation of miR-33
      is involved in this process. METHODS: An atherosclerosis model was established in
      apolipoprotein E-deficient (ApoE-/-) mice fed a Western diet, and THP-1 derived
      macrophages were used in this study. Hematoxylin-eosin and Oil Red O staining
      were used to quantify the atherosclerotic plaques. 1,1'-Dioctadecyl-3,3,3',3'
      tetramethylindocarbocyanine perchlorate labeled oxidized low-density lipoprotein
      binding assay and a Cholesterol Efflux Fluorometric Assay Kit were used to
      observe cholesterol uptake and efflux. The mRNA and protein levels of biomarkers
      associated with ER stress and cholesterol metabolism in atherosclerotic plaques
      and macrophages were evaluated by real-time PCR and western blotting,
      respectively. Immunofluorescence was used to observe alterations of ABCA1
      localization. Small interfering RNAs were used to knock down CHOP and miR-33 in
      macrophages to alter CHOP and miR-33 expression. RESULTS: Atherosclerotic lesions
      and systemic lipid levels were ameliorated after inhibition of ER stress
      (tauroursodeoxycholic acid) in vivo. In vitro studies confirmed that ER stress
      regulated the lipid catabolism of macrophages by promoting cholesterol uptake,
      inhibiting cholesterol efflux, and modulating the expression of related
      transporters. CHOP contributed to lipid metabolism disorder following ER stress.
      Furthermore, over-expression of miR-33 was involved in ER stress that induced
      lipid metabolism disorder in macrophages. These findings support a model of ER
      stress induction by oxidized low-density lipoprotein that affects macrophage
      lipid catabolism disorder. CONCLUSION: Our data shed new light on the
      relationship between ER stress and lipid metabolism in vivo and in vitro, and
      confirm that upregulation of miR-33 is involved in this process. The relationship
      between ER stress and miR-33 represents a novel target for the treatment of
      atherosclerosis.

PMID- 30092600
TI  - Survival following Multimodality Treatment Including Surgery for Stage IA-IIIB
      Small-Cell Lung Cancer.
AB  - BACKGROUND:  Prognosis in limited disease small-cell lung cancer (SCLC) after
      concurrent chemoradiotherapy is poor. While some studies show better survival
      after multimodality treatment including surgery, other trials failed to prove a
      surgery-related survival benefit. Therefore, this study investigated survival in
      stage IA-IIIB SCLC following surgery combined with chemotherapy and/or thoracic
      radiotherapy. METHODS:  We retrospectively reviewed all stage IA-IIIB SCLC
      patients without supraclavicular lymph node involvement at a single institution
      between January 1999 and August 2016 after multimodality treatment with curative
      intent. This comprised surgery consisting of primary tumor resection and
      systematic lymph node dissection combined with chemotherapy, chemoradiotherapy,
      or thoracic radiotherapy. Survival was determined using the Kaplan-Meier method,
      and differences were compared using log-rank tests. The risk of locoregional
      relapse was calculated. RESULTS:  A total of 47 patients (29 men, 18 women; mean
      age: 62 years) were included. Thirty-day mortality was 0%. Overall median
      survival was 56 months, and 2-, 3-, 5-, and 10-year survival rates were 69, 54,
      46, and 30%, respectively. The only significant prognostic factor (p = 0.006) was
      R0 resection (n = 40) increasing median survival to 64 versus 17 months in case
      of technical inoperability (n = 5). The risk of locoregional relapse was 2.5% (n
      = 1) after R0 resection. CONCLUSIONS:  Multimodality treatment including surgery
      was safe and led to considerable survival. R0 resection was the only factor
      extending survival. It could be achieved in most patients and was associated with
      a low risk of locoregional relapse. Prospective randomized controlled studies are
      needed to define best practice in stage IA-IIIB SCLC.

PMID- 30092601
TI  - Heart Murmurs.

PMID- 30092602
TI  - Robotic Transthoracic Esophagectomy in High-Volume Centers: Improving Outcome and
      Extending Indications.

PMID- 30092603
TI  - [Direct contact with patients].

PMID- 30092604
TI  - National guidance contributes to the high incidence of inpatient hypoglycaemia.
AB  - The seventh National Diabetes Inpatient Audit (NaDIA) 2017 was published in March
      2018, NaDIA is the annual snapshot audit of diabetes inpatient care in England
      and Wales. NaDIA 2017 found that 18% of hospital beds were occupied by a person
      with diabetes, an absolute increase of 3% from 2011. Moreover, the report
      identified that 4% of people with Type 1 diabetes mellitus developed the serious
      and preventable disorder of hospital-acquired diabetic ketoacidosis. Medication
      errors were common: 31% of people had at least one medication error, and this
      increased to 40% in those receiving insulin. Some 18% of inpatients with diabetes
      experienced at least one episode of hypoglycaemia (defined as a blood glucose of
      < 4.0 mmol/l). The incidence of severe hypoglycaemia was 7% (defined as a blood
      glucose < 3.0 mmol/l), but this increased to 26% in those with Type 1 diabetes
      [1]. Hypoglycaemia is not innocuous; there is considerable evidence that a blood
      glucose < 4.0 mmol/l is a risk factor for death in hospitalized persons [2-4].
      This article is protected by copyright. All rights reserved.

PMID- 30092605
TI  - Spring temperature, migration chronology, and nutrient allocation to eggs in
      three species of arctic-nesting geese: Implications for resilience to climate
      warming.
AB  - The macronutrients that Arctic herbivores invest in their offspring are derived
      from endogenous reserves of fat and protein (capital) that females build prior to
      the period of investment or from foods they consume concurrently with investment
      (income). The relative contribution from each source can be influenced by
      temporal and environmental constraints on a female's ability to forage on Arctic
      breeding areas. Warming temperatures and advancing Arctic phenology may alter
      those constraints. From 2011 to 2014, we examined relationships among spring
      temperature, timing of migration and reproduction, and the sources of nutrients
      females deposited in eggs for three sympatric species of geese that nested in
      northern Alaska. Compared to lesser snow geese (Anser caerulescens caerulescens)
      and greater white-fronted geese (Anser albifrons frontalis), black brant (Branta
      bernicla nigricans) were more likely to initiate follicle development during
      migration, resulting in fewer days between their arrival in the Arctic and the
      onset of incubation and requiring a relatively greater capital investment in
      eggs. Delaying follicle development until after their arrival in the Arctic
      provided snow geese and white-fronted geese an opportunity to forage near their
      nesting area and to deposit exogenous nutrients in eggs. With warmer spring
      temperatures, brant invested more capital in eggs, but snow geese invested less
      capital. Brant likely used capital to meet costs associated with earlier onset of
      follicle development when phenology was advanced, whereas snow geese used capital
      to compensate for poor foraging conditions during colder Arctic springs. Global
      warming is likely to reduce the quality of lower latitude marine habitats where
      brant acquire endogenous reserves and advancing Arctic phenology may increase
      their reliance on those reserves during reproduction. Near-term warming in
      northern Alaska may improve foraging conditions and favor the reproductive
      strategies of some herbivores such as snow geese and white-fronted geese that
      mainly invest Arctic nutrients in their offspring.

PMID- 30092606
TI  - How to reduce parental provision of unhealthy foods to 3- to 8-year-old children
      in the home environment? A systematic review utilizing the Behaviour Change Wheel
      framework.
AB  - BACKGROUND AND OBJECTIVE: The effectiveness of obesity prevention interventions
      to improve children's diet can be enhanced. Deconstructing past interventions can
      identify components with potential to change behaviour. This systematic review
      using the Behaviour Change Wheel aimed to examine the behaviour change content of
      interventions supporting parents of 3- to 8-year olds to reduce provision of
      unhealthy foods to children. METHODS: Ebscohost, Ovid, Scopus and Web of Science
      were searched. Eligible studies included controlled interventions with active
      parent involvement, at least one intervention strategy and outcome measure for
      unhealthy foods >=3 months from baseline. Seventeen interventions were included
      describing 18 intervention arms. RESULTS: Interventions frequently targeted
      parents' reflective motivation (n = 17) and psychological capability (n = 15),
      through education (n = 15) or enablement (n = 15) intervention functions and
      service provision (n = 18) policy category. Only 24 of the 93 behaviour change
      techniques were used with an average of five techniques used per intervention.
      CONCLUSIONS: Existing interventions achieving small reductions in unhealthy food
      intake are homogenous in approach. There is potential to utilize untapped
      behaviour change techniques, through comprehensive intervention design and
      behavioural analysis guided by the Behaviour Change Wheel. Interventions
      targeting opportunity through persuasion, modelling or environmental
      restructuring, and using different policy categories are urgently needed to
      provide an evidence base to inform policy and practice.

PMID- 30092607
TI  - N-glycosylation of the AMPA-type glutamate receptor regulates cell surface
      expression and tetramer formation affecting channel function.
AB  - The AMPA-type glutamate receptor (AMPA-R) plays a primary role in principal
      excitatory synaptic transmission and many neuronal functions including synaptic
      plasticity that underlie learning and memory. N-glycosylation is one of the major
      post-translational modifications of membrane proteins, but its specific roles in
      neurons remain largely unknown. AMPA-R subunits are N-glycosylated at their
      extracellular domains during their biosynthesis in the lumen of the endoplasmic
      reticulum and Golgi system. Six N-glycosylation sites are presumed to exist in
      the extracellular domain of GluA1, which is a member of the AMPA-R subunits. We
      observed that the intracellular trafficking and cell surface expression were
      strongly suppressed in the GluA1 mutants lacking N-glycans at N63/N363 in HEK293T
      cells. Multimer analysis using Blue Native-PAGE displayed the impaired tetramer
      formation in the glycosylation mutants (N63S and N363S), indicating that the mis
      transport was caused by impaired tetramer formation. N63S and N363S mutants were
      primarily degraded via the lysosomal pathway. Flag-tagged N363S GluA1, but not
      N63S GluA1, expressed in primary cortical neuron cultures prepared from GluA1
      knockout mice was observed to localize at the cell surface. Co-expression of
      GluA2 partially rescued tetramer formation and the cell surface expression of
      N363S GluA1 but not N63S GluA1, in HEK293T cells. Electrophysiological analysis
      also demonstrated functional heteromers of N363S GluA1 with GluA2. These data
      suggest that site-specific N-glycans on GluA1 subunit regulates tetramer
      formation, intracellular trafficking, and cell surface expression of AMPA-R. OPEN
      PRACTICES: Open Science: This manuscript was awarded with the Open Materials
      Badge. For more information see: https://cos.io/our-services/open-science
      badges/.

PMID- 30092608
TI  - Bioactive components in human milk are differentially associated with rates of
      lean and fat mass deposition in infants of mothers with normal vs. elevated BMI.
AB  - OBJECTIVE: To model breastfed infant growth and body composition patterns over
      the first 4 months with multiple bioactive components of human milk (HM) and
      clinical factors (including maternal BMI status), which are related to growth.
      METHODS: Longitudinal observation of infant growth and body composition from 0 to
      4 months among 41 predominantly breastfed infants (25 mothers of Normal-weight
      and 16 mothers with overweight/obesity). Fasted morning HM samples were collected
      at 5 time-points. Macronutrients, leptin, adiponectin, ghrelin, insulin,
      cytokines and n-6:n-3 esterified fatty acid ratio were measured. Infant weight
      for-length Z-score (WLZ) trajectory, fat-free mass (FFM) gain, fat mass gain and
      %fat gain were modelled controlling for clinical covariates. RESULTS: HM insulin
      negatively associated with WLZ trajectory among infants of NW mothers (P =
      0.028), but not associated with WLZ trajectory among infants of OW/Ob mothers. HM
      glucose (P < 0.001) was associated with slower rates of infant FFM gain. Infants
      of mothers with OW/Ob exhibited slower rates of FFM gain. HM protein, adiponectin
      and insulin concentrations, and n-6:n-3 ratio were all significant predictors in
      the model of infant fat mass gain (P < 0.03). Any amount of formula
      supplementation was associated with faster fat gain (P = 0.002). The model of
      %fat gain was similar to that of fat mass gain, excepting HM adiponectin was not
      a significant covariate, and a trend for maternal OW/Ob to correlate with faster
      %fat gain (P = 0.056). CONCLUSIONS: Bioactive components in HM may contribute to
      regulation of partitioning of body composition, and these contributions may
      differ between mothers of normal-weight vs. with OW/Ob.

PMID- 30092609
TI  - The effect of exercise training on intrahepatic triglyceride and hepatic insulin
      sensitivity: a systematic review and meta-analysis.
AB  - This systematic review and meta-analysis determined the impact of structured
      exercise training, and the influence of associated weight loss, on intrahepatic
      triglyceride (IHTG) in individuals with non-alcoholic fatty liver disease
      (NAFLD). It also examined its effect on hepatic insulin sensitivity in
      individuals with or at increased risk of NAFLD. Analyses were restricted to
      studies using magnetic resonance spectroscopy or liver biopsy for the measurement
      of IHTG and isotope-labelled glucose tracer for assessment of hepatic insulin
      sensitivity. Pooling data from 17 studies (373 exercising participants), exercise
      training for one to 24 weeks (mode: 12 weeks) elicits an absolute reduction in
      IHTG of 3.31% (95% CI: -4.41 to -2.22%). Exercise reduces IHTG independent of
      significant weight change (-2.16 [-2.87 to -1.44]%), but benefits are
      substantially greater when weight loss occurs (-4.87 [-6.64 to -3.11]%).
      Furthermore, meta-regression identified a positive association between percentage
      weight loss and absolute reduction in IHTG (beta = 0.99 [0.62 to 1.36], P <
      0.001). Pooling of six studies (94 participants) suggests that exercise training
      also improves basal hepatic insulin sensitivity (mean change in hepatic insulin
      sensitivity index: 0.13 [0.05 to 0.21] mg m-2  min-1 per MUU mL-1 ), but
      available evidence is limited, and the impact of exercise on insulin-stimulated
      hepatic insulin sensitivity remains unclear.

PMID- 30092610
TI  - Why we need epidemiologic studies of polycystic ovary syndrome in Africa.
AB  - The primary objective of the Ghana Polycystic Ovary Syndrome Epidemiology and
      Phenotype (Ghana-PEP) study will be to assess the relevance and phenotypic
      distribution of polycystic ovarian syndrome (PCOS) in a medically unbiased
      population of reproductive-aged women. In addition, the study will also attempt
      to identify sociodemographic, environmental, and psychological factors that may
      play a role in the development of PCOS phenotype. The study aims to recruit 990
      randomly selected women aged 18-45 years living in Nsawam, the district capital
      of the Nsawam-Adoagyiri Municipality, in the Eastern region of Ghana.
      Participants will complete a questionnaire with the aid of trained personnel,
      undergo a physical examination, and undergo ultrasonography and biochemical
      evaluations relevant to PCOS. It is anticipated that the study will provide the
      population prevalence and phenotypes, and distribution of PCOS.

PMID- 30092611
TI  - The stated conclusions are contradicted by the data, based on inappropriate
      statistics, and should be corrected: comment on 'intervention for childhood
      obesity based on parents only or parents and child compared with follow-up
      alone'.

PMID- 30092612
TI  - Enhancer function regulated by combinations of transcription factors and
      cofactors.
AB  - Regulation of the expression of diverse genes is essential for making possible
      the complexity of higher organisms, and the temporal and spatial regulation of
      gene expression allows for the alteration of cell types and growth patterns. A
      critical component of this regulation is the DNA sequence-specific binding of
      transcription factors (TFs). However, most TFs do not independently participate
      in gene transcriptional regulation, because they lack an effector function.
      Instead, TFs are thought to work by recruiting cofactors, including Mediator
      complex (Mediator), chromatin-remodeling complexes (CRCs), and histone-modifying
      complexes (HMCs). Mediator associates with the majority of transcribed genes and
      acts as an integrator of multiple signals. On the other hand, CRCs and HMCs are
      selectively recruited by TFs. Although all the pairings between TFs and CRCs or
      HMCs are not fully known, there are a growing number of established TF-CRC and TF
      HMC combinations. In this review, we focused on the most important of these
      pairings and discuss how they control gene expression.

PMID- 30092613
TI  - Opposing roles of IgM and IgD in BCR-induced B-cell survival.
AB  - The B-cell receptor (BCR) transmits a tonic survival signal in the absence of
      antigen stimulation and an antigen-triggered survival signal. Mature B cells
      express two types of BCR, IgM and IgD, but it remains unclear how B-cell survival
      is differentially regulated by these two receptors. We found that, whereas cross
      linking IgM on spleen B cells greatly enhanced their survival, cross-linking IgD
      did not enhance, but rather decreased, their survival. Consistently, cross
      linking both IgM and IgD only moderately enhanced B-cell survival, suggesting
      that IgM and IgD play opposing roles in B-cell survival induced by BCR
      stimulation. Based on these and additional experimental results, we present a
      mathematical model integrating IgM- and IgD-mediated survival signals. Our model
      shows that IgD can transmit a tonic survival signal in the absence of antigen
      stimulation but cross-linking IgD not only does not generate a survival signal
      but also disrupts its tonic signal, resulting in inhibition of B-cell survival.
      These results suggest that IgD attenuates BCR-induced survival in mature B cells,
      presumably to restrain B-cell response to weak and/or self-antigens and prevent
      nonspecific B-cell activation and autoimmunity.

PMID- 30092614
TI  - A helpful technique for increasing the size of a tracheostomy window in patients
      with calcified or challenging tracheas utilising a Kerrison punch forceps.

PMID- 30092616
TI  - Lysosome biogenesis in health and disease.
AB  - This review focuses on the pathways that regulate lysosome biogenesis and that
      are implicated in numerous degenerative storage diseases, including lysosomal
      storage disorders and late-onset neurodegenerative diseases. Lysosomal proteins
      are synthesized in the endoplasmic reticulum and trafficked to the endolysosomal
      system through the secretory route. Several receptors have been characterized
      that execute post-Golgi trafficking of lysosomal proteins. Some of them recognize
      their cargo proteins based on specific amino acid signatures, others based on a
      particular glycan modification that is exclusively found on lysosomal proteins.
      Nearly all receptors serving lysosome biogenesis are under the transcriptional
      control of transcription factor EB (TFEB), a master regulator of the lysosomal
      system. TFEB coordinates the expression of lysosomal hydrolases, lysosomal
      membrane proteins, and autophagy proteins in response to pathways sensing
      lysosomal stress and the nutritional conditions of the cell among other stimuli.
      TFEB is primed for activation in lysosomal storage disorders but surprisingly its
      function is impaired in some late-onset neurodegenerative storage diseases like
      Alzheimer's and Parkinson's, because of specific detrimental interactions that
      limit TFEB expression or activation. Thus, disrupted TFEB function presumably
      plays a role in the pathogenesis of these diseases. Multiple studies in animal
      models of degenerative storage diseases have shown that exogenous expression of
      TFEB and pharmacological activation of endogenous TFEB attenuate disease
      phenotypes. These results highlight TFEB-mediated enhancement of lysosomal
      biogenesis and function as a candidate strategy to counteract the progression of
      these diseases. This article is part of the Special Issue "Lysosomal Storage
      Disorders".

PMID- 30092615
TI  - The NICE classification for 'Ultra-radical (extensive) surgery for advanced
      ovarian cancer' guidance does not meaningfully predict postoperative
      complications: a cohort study.
AB  - OBJECTIVE: To determine which descriptors of cytoreductive surgical extent in
      advanced ovarian cancer (AOC) best predict postoperative morbidity. DESIGN:
      Retrospective notes review. SETTING: A gynaecological cancer centre in the UK.
      POPULATION: Six hundred and eight women operated on for AOC over a period of 114
      months at a tertiary cancer centre, between 16 August 2007 and 16 February 2017.
      METHODS: Outcome data were analysed by six approaches to classify the extent of
      surgery: standard/ultra-radical surgery; standard/radical/supra-radical surgery;
      presence/absence of gastrointestinal resections; low/intermediate/high surgical
      complexity score (SCS); presence of bowel anastomoses and/or diaphragmatic
      surgery; and the presence/absence of multiple bowel resections. MAIN OUTCOME
      MEASURES: Major (grades 3-5) postoperative morbidity and mortality. RESULTS:
      Forty-three (7.1%) patients experienced major complications. Grade-5
      complications occurred in six patients (1.0%). Patients who underwent multiple
      bowel resections had a relative risk (RR) of 7.73 (95% confidence interval, 95%
      CI 3.92-15.26), patients with a high SCS had an RR of 6.12 (95% CI 3.25-11.52),
      patients with diaphragmatic surgery and gastrointestinal anastomosis had an RR of
      5.57 (95% CI 2.65-11.72), patients with 'any gastrointestinal resection' had an
      RR of 4.69 (95% CI 2.66-8.24), patients with ultra-radical surgery had an RR of
      4.65 (95% CI 2.26-8.79), and patients with supra-radical surgery had an RR of
      4.20 (95% CI 2.35-7.51) of grades 3-5 morbidity, compared with patients
      undergoing standard surgery as defined by the National Institute for Health and
      Care Excellence (NICE) in the UK. No significant difference was seen in the rate
      of major morbidity between standard (6/59, 10.2%) and ultra-radical (9/81, 11.1%)
      surgery within the cohort who had intermediate complex surgery (P > 0.05).
      CONCLUSIONS: The numbers of procedures performed significantly correlate with
      major morbidity. The number of procedures performed better predicted major
      postoperative morbidity than the performance of certain 'high risk' procedures.
      We recommend using SCS to define a higher risk operation. NICE should re-evaluate
      the use of the term 'ultra-radical' surgery. TWEETABLE ABSTRACT: Multiple bowel
      resection is the best predictor of morbidity and is more predictive than 'ultra
      radical surgery'.

PMID- 30092617
TI  - Study of Some Zanthoxylum Species by Chemical and DNA Analysis Approaches.
AB  - The authentication and traceability of spices is a major concern for industrials
      and consumers. We focused on species from Zanthoxylum genera which are used for
      many different applications by local populations and also for trading as spices
      (dried pericarps or whole fruits). In this case, literature gives contradictory
      data about botanical names, and commercial labelling is often confusing. We
      studied commercial fruits pericarps extracts obtained by supercritical CO2 and
      analyzed them by GC/MS. The very complex volatile and semi volatile fractions
      composition of each extract is described. The barcoding method including
      molecular biology and phylogenetic analyses was also developed in order to check
      the commercial botanical identification of the raw material. This is a robust
      method to identify species in berries samples. We used one genetic marker to
      identify two Rutaceae clusters, including several species of Zanthoxylum genus.
      These results indicate that Fagara and Zanthoxylum groups could be considered as
      two different genera. Combination of chemical analysis and DNA analysis provides
      an original approach to increase chemical and botanical Zanthoxylum genus
      knowledge.

PMID- 30092618
TI  - Making dietary changes following a diagnosis of prediabetes: a qualitative
      exploration of barriers and facilitators.
AB  - AIM: To explore the experiences of people recently diagnosed with prediabetes and
      overweight or obese in making dietary changes following a six-month primary care
      nurse-delivered dietary intervention pilot. METHODS: Semi-structured interviews
      were conducted with 20 participants, purposefully selected to ensure a mix of
      ethnicity, gender and glycaemic outcome. Thematic analysis of interview data was
      undertaken. RESULTS: Participants described feeling shocked when they received
      the diagnosis of prediabetes. Three core themes, each containing subthemes,
      emerged: (i) supportive factors - determination not to develop diabetes, clear
      information and manageable strategies, and supportive relationships; (ii)
      barriers - lack of family support, financial constraints, social expectations
      around food, and chronic health issues; and (iii) overcoming challenges - growing
      and sharing food, using frozen vegetables and planning. Challenges related to
      cultural expectations around providing and partaking of food were more evident
      for indigenous Maori participants. CONCLUSIONS: A diagnosis of prediabetes
      provides a window of opportunity for healthcare professionals to work with those
      diagnosed and their families to make healthful dietary changes. Dietary guidance
      is likely to be most effective when individuals' life circumstances are taken
      into account. Clear information and supportive relationships to facilitate
      lifestyle change are extremely important. (Clinical Trials Registry No; ANZCTR
      ACTRN1261500080656).

PMID- 30092619
TI  - Clinical handover practices among healthcare practitioners in acute care
      services: A qualitative study.
AB  - AIMS AND OBJECTIVES: To examine clinical handover practices in acute care
      services in Ireland. Objectives were to examine clinical handover practices
      between and within teams and between shifts, to identify resources and supports
      to enhance handover effectiveness and to identify barriers and facilitators of
      effective handover. BACKGROUND: Clinical handover is a high-risk activity, and
      ineffective handover practice constitutes a risk to patient safety. Evidence
      suggests that handover effectiveness is achieved through staff training and
      standardised handover protocols. DESIGN: The study design was qualitative
      descriptive using inductive analysis. METHODS: The study involved a series of
      focus group discussions and interviews among a sample of healthcare practitioners
      recruited from 12 urban and regional acute hospitals in Ireland. A total of 116
      healthcare professionals took part in 28 interviews and 13 focus group
      discussions. We analysed the data using the directed content analysis method.
      RESULTS: Data collection generated rich qualitative data, yielding five
      categories from which two broad themes emerged: "policy and practice" and
      "handover effectiveness." The themes and their associated categories indicate
      that there is limited organisational-level policy and limited explicit training
      in clinical handover, that medical and nursing handovers are separate activities
      with somewhat different purposes and different modes of execution, and that
      several factors in the acute care setting, including location, timing and
      documentation, act as either barriers or enablers to handover effectiveness.
      CONCLUSION: The evidence in the current study suggests that clinical handover
      merits increased level of prominence in hospital policies or operating
      procedures. Medical and nursing handover practices represent distinct activities
      in their content and execution that may be related to cultural and organisational
      factors. RELEVANCE TO CLINICAL PRACTICE: Achieving multidisciplinary team
      handover requires a change in embedded traditional practices. Several aspects of
      the clinical handover activities of nursing and medical staff appear to diverge
      from best-practice evidence.

PMID- 30092620
TI  - The association between Helicobacter pylori seropositivity and low birthweight in
      a Sudanese maternity hospital.
AB  - OBJECTIVE: To investigate the association between Helicobacter pylori
      seropositivity and low birthweight (LBW). METHODS: The present case-control study
      was conducted at a Sudanese maternity hospital from September 1 to December 30,
      2015. Patients who delivered single neonates with LBW (>500 g but <2500 g) and
      the subsequent singleton delivery with birthweight of 2500-4000 g were included.
      A questionnaire was used to collect medical and obstetric data. The presence of
      malarial parasites in peripheral, placental, and umbilical cord samples was
      investigated using blood films. The presence of H. pylori immunoglobulin G (IgG)
      in maternal and umbilical cord serum samples was determined by enzyme-linked
      immunosorbent assay. RESULTS: The study included 87 patients in each of the LBW
      and control groups. Maternal serum tested positive for H. pylori IgG among 66
      (75.9%) and 48 (55.2%) patients in the LBW and control groups (P=0.006); no
      malarial parasites were observed. Similarly, umbilical cord serum tested positive
      for H. pylori IgG among 66 (75.9%) and 34 (39.1%) patients in the LBW and control
      groups (P<0.001). Maternal H. pylori IgG seropositivity (OR 3.2, 95% CI 1.4-7.2;
      P=0.003) and umbilical cord H. pylori IgG seropositivity (OR 2.4, 95% confidence
      interval 2.1-10.2; P<0.001) were significantly associated with LBW. CONCLUSION:
      Seropositivity for H. pylori IgG was associated with LBW.

PMID- 30092621
TI  - Incidence, risk factors and prevention of stoma site incisional hernias: a
      systematic review and meta-analysis.
AB  - AIM: Stoma reversal might lead to a stoma site incisional hernia. Recently,
      prophylactic mesh reinforcement of the stoma site has gained increased attention,
      supporting the need for accurate data on the incidence of and risk factors for
      stoma site incisional hernia and to identify high-risk patients. The aim of this
      study was to assess incidence, risk factors and prevention of stoma site
      incisional hernias. METHOD: Embase, MEDLINE, Web of Science, Cochrane and Google
      Scholar databases were searched. Studies reporting the incidence of stoma site
      incisional hernia after stoma reversal were included. Study quality was assessed
      with the Newcastle-Ottawa Scale and Cochrane risk of bias tool. Data on
      incidence, risk factors and prophylactic mesh reinforcement were extracted.
      RESULTS: Of 1440 articles found, 33 studies comprising 4679 reversals were
      included. The overall incidence of incisional hernia was 6.5% [range 0%-38%,
      median follow-up 27.5 (17.54-36) months]. Eleven studies assessed stoma site
      incisional hernia as the primary end-point, showing an incidence of 17.7% [range
      1.7%-36.1%, median follow-up 28 (15.25-51.70) months]. Body mass index, diabetes
      and surgery for malignant disease were found to be independent risk factors, as
      derived from eight studies. Two retrospective comparative cohort studies showed
      significantly lower rates of stoma site incisional hernia with prophylactic mesh
      reinforcement compared with nonmesh controls [6.4% vs 36.1% (P = 0.001); 3% vs
      19% (P = 0.04)]. CONCLUSION: Stoma site incisional hernia should not be
      underestimated as a long-term problem. Body mass index, diabetes and malignancy
      seem to be potential risk factors. Currently, limited data are available on the
      outcomes of prophylactic mesh reinforcement to prevent stoma site incisional
      hernia.

PMID- 30092622
TI  - Overexpression of the Na+ /Ca2+ exchanger influences ouabain-mediated spontaneous
      Ca2+ activity but not positive inotropy.
AB  - Administration of digitalis in heart failure (HF) increases quality of life but
      does not carry a prognostic benefit. Digitalis is an indirect inhibitor of the
      Na+ /Ca2+ exchanger (NCX), which is overexpressed in HF. We therefore used the
      cardiac glycoside ouabain in Ca2+ imaging experiments and patch-clamp experiments
      in isolated ventricular myocytes from nonfailing transgenic NCX overexpressor
      mice (OE). In field-stimulated myocytes, ouabain (1-100 MUm) increased the
      amplitude of the Ca2+ transient in OE and wild-type (WT) similarly. Ouabain
      mediated spontaneous Ca2+ -activity was significantly more pronounced in OE
      compared to WT myocytes at higher concentrations (100 MUm). Also, at very high
      concentrations (1000 MUm) of ouabain, the number of cells with hypercontraction
      leading to cell death was higher in OE. Ouabain (10 MUm) shortened the action
      potential duration in both genotypes. Our findings suggest that the proarrhythmic
      but not the inotropic effects of cardiac glycosides are enhanced by increased NCX
      expression. This may offer an explanation for the observed lack of prognostic
      benefit but increased quality of life in HF, which is accompanied by NCX
      upregulation.

PMID- 30092623
TI  - Prediction of Acquired Taxane Resistance Using a Personalized Pathway-Based
      Machine Learning Method.
AB  - Purpose: This study was conducted to develop and validate an individualized
      prediction model for automated detection of acquired taxane resistance (ATR).
      Materials and Methods: Penalized regression, combined with an individualized
      pathway score algorithm, was applied to construct a predictive model using
      publically available genomic cohorts of ATR and intrinsic taxane resistance
      (ITR). To develop a model with enhanced generalizability, we merged multiple ATR
      studies then updated the learning parameter via robust cross-study validation.
      Results: For internal cross-study validation, the ATR model produced a perfect
      performance with an overall area under the receiver operating curve (AUROC) of
      1.000 with an area under the precision-recall curve (AUPRC) of 1.000, a Brier
      score of 0.007, a sensitivity and a specificity of 100%. The model showed an
      excellent performance on two independent blind ATR cohorts (overall AUROC of
      0.940, AUPRC of 0.940, a Brier score of 0.127). When we applied our algorithm to
      two large-scale pharmacogenomic resources for ITR, the Cancer Genome Project
      (CGP) and the Cancer Cell Line Encyclopedia (CCLE), an overall ITR cross-study
      AUROC was 0.70, which is a far better accuracy than an almost random level
      reported by previous studies. Furthermore, this model had a high transferability
      on blind ATR cohorts with an AUROC of 0.69, suggesting that general predictive
      features may be at work across both ITR and ATR. Conclusion: We successfully
      constructed a multi-study-derived personalized prediction model for ATR with
      excellent accuracy, generalizability and transferability.

PMID- 30092625
TI  - Imidazole Antifungal Drugs Inhibit the Cell Proliferation and Invasion of Human
      Breast Cancer Cells.
AB  - Breast cancer is currently the most prevalent cancer in women, and its incidence
      increases every year. Azole antifungal drugs were recently found to have
      antitumor efficacy in several cancer types. They contain an imidazole
      (clotrimazole and ketoconazole) or a triazole (fluconazole and itraconazole)
      ring. Using human breast adenocarcinoma cells (MCF-7 and MDA-MB-231), we
      evaluated the effects of azole drugs on cell proliferation, apoptosis, cell
      cycle, migration, and invasion, and investigated the underlying mechanisms.
      Clotrimazole and ketoconazole inhibited the proliferation of both cell lines
      while fluconazole and itraconazole did not. In addition, clotrimazole and
      ketoconazole inhibited the motility of MDA-MB-231 cells and induced G1-phase
      arrest in MCF-7 and MDA-MB-231 cells, as determined by cell cycle analysis and
      immunoblot data. Moreover, Transwell invasion and gelatin zymography assays
      revealed that clotrimazole and ketoconazole suppressed invasiveness through the
      inhibition of matrix metalloproteinase 9 in MDA-MB-231 cells, although no
      significant changes in invasiveness were observed in MCF-7 cells. There were no
      significant changes in any of the observed parameters with fluconazole or
      itraconazole treatment in either breast cancer cell line. Taken together,
      imidazole antifungal drugs showed strong antitumor activity in breast cancer
      cells through induction of apoptosis and G1 arrest in both MCF-7 and MDA-MB-231
      cells and suppression of invasiveness via matrix metalloproteinase 9 inhibition
      in MDA-MB-231 cells. Imidazole drugs have well-established pharmacokinetic
      profiles and known toxicity, which can make these generic drugs strong candidates
      for repositioning as antitumor therapies.

PMID- 30092627
TI  - Synergistic Rewiring of Carbon Metabolism and Redox Metabolism in Cytoplasm and
      Mitochondria of Aspergillus oryzae for Increased l-Malate Production.
AB  - l-Malate is an important platform chemical that has extensive applications in the
      food, feed, and wine industries. Here, we synergistically engineered the carbon
      metabolism and redox metabolism in the cytosol and mitochondria of a previously
      engineered Aspergillus oryzae to further improve the l-malate titer and decrease
      the byproduct succinate concentration. First, the accumulation of the
      intermediate pyruvate was eliminated by overexpressing a pyruvate carboxylase
      from Rhizopus oryzae in the cytosol and mitochondria of A. oryzae, and
      consequently, the l-malate titer increased 7.5%. Then, malate synthesis via
      glyoxylate bypass in the mitochondria was enhanced, and citrate synthase in the
      oxidative TCA cycle was downregulated by RNAi, enhancing the l-malate titer by
      10.7%. Next, the exchange of byproducts (succinate and fumarate) between the
      cytosol and mitochondria was regulated by the expression of a dicarboxylate
      carrier Sfc1p from Saccharomyces cerevisiae in the mitochondria, which increased
      l-malate titer 3.5% and decreased succinate concentration 36.8%. Finally, an NADH
      oxidase from Lactococcus lactis was overexpressed to decrease the NADH/NAD+
      ratio, and the engineered A. oryzae strain produced 117.2 g/L l-malate and 3.8
      g/L succinate, with an l-malate yield of 0.9 g/g corn starch and a productivity
      of 1.17 g/L/h. Our results showed that synergistic engineering of the carbon and
      redox metabolisms in the cytosol and mitochondria of A. oryzae effectively
      increased the l-malate titer, while simultaneously decreasing the concentration
      of the byproduct succinate. The strategies used in our work may be useful for the
      metabolic engineering of fungi to produce other industrially important chemicals.

PMID- 30092626
TI  - Tenovin-1 Induces Senescence and Decreases Wound-Healing Activity in Cultured Rat
      Primary Astrocytes.
AB  - Brain aging induces neuropsychological changes, such as decreased memory
      capacity, language ability, and attention; and is also associated with
      neurodegenerative diseases. However, most of the studies on brain aging are
      focused on neurons, while senescence in astrocytes has received less attention.
      Astrocytes constitute the majority of cell types in the brain and perform various
      functions in the brain such as supporting brain structures, regulating blood
      brain barrier permeability, transmitter uptake and regulation, and immunity
      modulation. Recent studies have shown that SIRT1 and SIRT2 play certain roles in
      cellular senescence in peripheral systems. Both SIRT1 and SIRT2 inhibitors delay
      tumor growth in vivo without significant general toxicity. In this study, we
      investigated the role of tenovin-1, an inhibitor of SIRT1 and SIRT2, on rat
      primary astrocytes where we observed senescence and other functional changes.
      Cellular senescence usually is characterized by irreversible cell cycle arrest
      and induces senescence-associated beta-galactosidase (SA-beta-gal) activity.
      Tenovin-1-treated astrocytes showed increased SA-beta-gal-positive cell number,
      senescence-associated secretory phenotypes, including IL-6 and IL-1beta, and cell
      cycle-related proteins like phospho-histone H3 and CDK2. Along with the molecular
      changes, tenovin-1 impaired the wound-healing activity of cultured primary
      astrocytes. These data suggest that tenovin-1 can induce cellular senescence in
      astrocytes possibly by inhibiting SIRT1 and SIRT2, which may play particular
      roles in brain aging and neurodegenerative conditions.

PMID- 30092629
TI  - Development of a Nanobody-AviTag Fusion Protein and Its Application in a
      Streptavidin-Biotin-Amplified Enzyme-Linked Immunosorbent Assay for Ochratoxin A
      in Cereal.
AB  - Ochratoxin A (OTA) is a common food contaminant that threatens consumers' safety
      and health. A sensitive and selective biotin-streptavidin-amplified enzyme-linked
      immunosorbent assay (BA-ELISA) for OTA using a nanobody-AviTag fusion protein (Nb
      AviTag) was developed in this study. The prokaryotic expression vector Nb28
      AviTag-pAC6 for Nb-AviTag was constructed, followed by transformation to the
      AVB101 cells for antibody expression and in vivo biotinylation. The purified Nb28
      AviTag was used to establish the BA-ELISA and the procedures for this Nb-AviTag
      based BA-ELISA were optimized. The Nb-AviTag-based BA-ELISA exhibited the half
      maximal inhibitory concentration (IC50) of 0.14 ng mL-1 and the limit of
      detection (LOD = IC10) of 0.028 ng mL-1 for OTA basing on the optimized
      experiment parameters. The assay sensitivity was improved 4.6 times and 4.3 times
      compared to Nb-based ELISA, respectively. This method had LODs of 1.4 MUg kg-1 in
      barley, 0.56 MUg kg-1 in oats, and 0.84 MUg kg-1 in rice for OTA. The average
      recovery percent was in a range of 84-137%, and the relative standard derivation
      percent ranged from 0.64% to 7.8%. The content of OTA in contaminated cereal
      samples was determined by both the developed Nb-AviTag-based method and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). The results demonstrated that
      the Nb-AviTag was a robust and promising bioreceptor in highly sensitive
      detection of OTA and other low molecular weight compounds using BA system.

PMID- 30092628
TI  - Dissolved Mineral Ash Generated by Vegetation Fire Is Photoactive under the Solar
      Spectrum.
AB  - Vegetation fire generates vast amounts of mineral ash annually that can be
      readily mobilized by water or wind erosion. Little is known about the
      photoactivity of dissolved mineral ash in aquatic systems and its ability to
      mediate redox reactions of environmental pollutants. This study reports that
      dissolved mineral ash derived from pyrolysis of biomass is photoactive under
      simulated sunlight, generating reactive oxygen species. It can mediate the
      photoreduction of hexavalent chromium (Cr(VI)) in the presence of electron
      donors; for example, phenols and dissolved organic matter, at pH 4.7. The
      reaction kinetics followed the Langmuir-Hinshelwood model, suggesting a
      heterogeneous photocatalytic reaction. The enhancement of reduction efficiency
      was linearly correlated with the one-electron reduction potential of phenols. The
      synergy between dissolved mineral ash and phenols is attributed to the inhibition
      of electron-hole recombination. The reduction rate decreases with increasing
      solution pH, owing to the decreased reduction potential and surface adsorption of
      Cr(VI). The silicon and silicon carbide components are most likely responsible
      for the photocatalytic activity of dissolved mineral ash. Our results suggest
      that dissolved mineral ash is a natural photocatalyst that can mediate redox
      reactions of pollutants in sunlit aquatic systems, playing an overlooked role in
      natural attenuation and aquatic photochemistry.

PMID- 30092624
TI  - 2017 KASL clinical practice guidelines management of hepatitis C: Treatment of
      chronic hepatitis C.

PMID- 30092630
TI  - Enhancing the Nutritive Value of Corn Whole Stillage for Pigs via Pretreatment
      and Predigestion.
AB  - Corn DDGS is poorly digested by pigs. Pretreatment or predigestion of whole
      stillage (WS; slurry material from which DDGS is derived) can potentially improve
      corn DDGS digestibility. Thus, a study was conducted to determine the effects of
      pretreating WS with heat (160  degrees C and 70 psi for 20 min) alone or in
      combination with citric acid (10 g/L; CA), sulfuric acid (90 mM; H2SO4), or
      ammonia (1%), without or with subsequent multienzymatic hydrolysis for 24 h, on
      porcine digestibility. Dried untreated, heat-pretreated, CA-pretreated, H2SO4
      pretreated, and ammonia-pretreated WS contained 23, 21, 12 19, and 18% total
      nonstarch polysaccharides, respectively. Pretreatment increased in vitro
      digestibility of dry matter of WS by ~11 (CA) to ~15% units (ammonia).
      Multienzyme hydrolysis increased in vitro digestibility of dry matter of WS by ~6
      (ammonia-treated WS) to ~18% units (untreated WS). Thus, pretreatment or
      predigestion can improve the digestibility of WS and hence the resulting DDGS.

PMID- 30092631
TI  - Cargo Retention inside P22 Virus-Like Particles.
AB  - Viral protein cages, with their regular and programmable architectures, are
      excellent platforms for the development of functional nanomaterials. The ability
      to transform a virus into a material with intended structure and function relies
      on the existence of a well-understood model system, a noninfectious virus-like
      particle (VLP) counterpart. Here, we study the factors important to the ability
      of P22 VLP to retain or release various protein cargo molecules depending on the
      nature of the cargo, the capsid morphology, and the environmental conditions.
      Because the interaction between the internalized scaffold protein (SP) and the
      capsid coat protein (CP) is noncovalent, we have studied the efficiency with
      which a range of SP variants can dissociate from the interior of different P22
      VLP morphologies and exit by traversing the porous capsid. Understanding the
      types of cargos that are either retained or released from the P22 VLP will aid in
      the rational design of functional nanomaterials.

PMID- 30092632
TI  - Prevention of Atherosclerosis by Berries: The Case of Blueberries.
AB  - Berry consumption has been associated with cardiovascular disease prevention in
      recent years. Atherosclerosis is one of the major causes of cardiovascular
      diseases. However, research on the prevention of atherosclerosis through
      consuming individual whole berries, specifically direct evidence, remains scarce.
      Therefore, further elucidating the role that berries play in the prevention of
      atherosclerosis is warranted. In this perspective, blueberries were selected to
      articulate research strategies for studying atheroprotective effects of berries.
      Studies from human subjects and various animal models are summarized. The
      mechanisms by which blueberries may act, through reducing oxidative stress,
      decreasing inflammation, improving endothelial dysfunction, regulating
      cholesterol accumulation and trafficking, along with potentially influencing gut
      microbiota, are also discussed. Blueberries contain high levels of polyphenolic
      compounds, which were widely indicated as major bioactive compounds. Nonetheless,
      the metabolites/catabolites after blueberry consumption, such as simple phenolic
      acids, rather than original compounds in berries, may be the actual in vivo
      bioactive compounds. Future research should focus on obtaining more direct
      evidence, preferably in humans, understanding of the mechanisms of action at the
      molecular level, and identifying bioactive compounds as well as which compounds
      act synergistically to convey health benefits. The research strategy discussed
      here may also be applied to the studies of other fruits and berries.

PMID- 30092633
TI  - Novel Hybrid Input Part Using Riboswitch and Transcriptional Repressor for Signal
      Inverting Amplifier.
AB  - Genetic circuits are composed of input, logic, and output parts. Construction of
      complex circuits for practical applications requires numerous tunable genetic
      parts. However, the limited diversity and complicated tuning methods used for the
      input parts hinders the scalability of genetic circuits. Therefore, a new type of
      input part is required that responds to diverse signals and enables easy tuning.
      Here, we developed RNA-protein hybrid input parts that combine a riboswitch and
      orthogonal transcriptional repressors. The hybrid inputs successfully regulated
      the transcription of an output in response to the input signal detected by the
      riboswitch and resulted in signal inversion because of the expression of
      transcriptional repressors. Dose-response parameters including fold-change and
      half-maximal effective concentration were easily modulated and amplified simply
      by changing the promoter strength. Furthermore, the hybrid input detected both
      exogenous and endogenous signals, indicating potential applications in metabolite
      sensing. This hybrid input part could be highly extensible considering the rich
      variety of components.

PMID- 30092634
TI  - Heterostructure WSe2-Ga2O3 Junction Field-Effect Transistor for Low-Dimensional
      High-Power Electronics.
AB  - Layered materials separated from each bulk crystal can be assembled to form a
      strain-free heterostructure by using the van der Waals interaction. We
      demonstrated a heterostructure n-channel depletion-mode beta-Ga2O3 junction field
      effect transistor (JFET) through van der Waals bonding with an exfoliated p-WSe2
      flake. Typical diode characteristics with a high rectifying ratio of ~105 were
      observed in a p-WSe2/n-Ga2O3 heterostructure diode, where WSe2 and beta-Ga2O3
      were obtained by mechanically exfoliating each crystal. Layered JFETs exhibited
      an excellent IDS- VDS output as well as IDS- VGS transfer characteristics with a
      high on/off ratio (~108) and low subthreshold swing (133 mV/dec). Saturated
      output currents were observed with a threshold voltage of -5.1 V and a three
      terminal breakdown voltage of +144 V. Electrical performances of the fabricated
      heterostructure JFET were maintained at elevated temperatures with outstanding
      air stability. Our WSe2-Ga2O3 heterostructure JFET paves the way to the low
      dimensional high-power devices, enabling miniaturization of the integrated power
      electronic systems.

PMID- 30092636
TI  - Dynamics of Disordered Proteins under Confinement: Memory Effects and Internal
      Friction.
AB  - Many proteins are disordered under physiological conditions. How efficiently they
      can search for their cellular targets and how fast they can fold upon target
      binding is determined by their intrinsic dynamics, which have thus attracted much
      recent attention. Experiments and molecular simulations show that the inherent
      reconfiguration timescale for unfolded proteins has a solvent friction component
      and an internal friction component, and the microscopic origin of the latter,
      along with its proper mathematical description, has been a topic of considerable
      debate. Internal friction varies across different proteins of comparable length
      and increases with decreasing denaturant concentration, showing that it depends
      on how compact the protein is. Here we report on a systematic atomistic
      simulation study of how confinement, which induces a more compact unfolded state,
      affects dynamics and friction in disordered peptides. We find that the average
      reconfiguration timescales increase exponentially as the peptide's spatial
      dimensions are reduced; at the same time, confinement broadens the spectrum of
      relaxation timescales exhibited by the peptide. There are two important
      implications of this broadening: First, it limits applicability of the common
      Rouse and Zimm models with internal friction, as those models attempt to capture
      internal friction effects by introducing a single internal friction timescale.
      Second, the long-tailed distribution of relaxation times leads to anomalous
      diffusion effects in the dynamics of intramolecular distances. Analysis and
      interpretation of experimental signals from various measurements that probe
      intramolecular protein dynamics (such as single-molecule fluorescence correlation
      spectroscopy and single-molecule force spectroscopy) rely on the assumption of
      diffusive dynamics along the distances being probed; hence, our results suggest
      the need for more general models allowing for anomalous diffusion effects.

PMID- 30092635
TI  - Cs4PbX6 (X = Cl, Br, I) Nanocrystals: Preparation, Water-Triggered Transformation
      Behavior, and Anti-Counterfeiting Application.
AB  - As a promising material, Cs4PbX6 (X = Cl, Br, I) nanocrystals (NCs) have
      attracted much attention. However, their luminescent property is still under
      debate. In this work, we first systematically studied the colloidal preparation
      of Cs4PbX6 NCs. It is found that the critical parameter for the formation of
      Cs4PbX6 NCs is the ratio between Cs and Pb. Pure Cs4PbX6 NCs are nonluminescent.
      The luminescence property of previous reported Cs4PbX6 NCs may come from the
      impurity of luminescent CsPbX3 NCs. No coexistence of both Cs4PbX6 and CsPbX3
      phase has been found in one single nanoparticle. The water-triggered
      transformation from nonluminescent Cs4PbX6 NCs to luminescent CsPbX3 NCs has been
      quantitatively studied. The potential application of Cs4PbX6 NCs in humidity
      sensor and anticounterfeiting have been demonstrated. This work is important
      because it not only confirmed the nonluminescent nature of Cs4PbX6 NCs but also
      demonstrated the potential application of such NCs.

PMID- 30092637
TI  - Ionic Conductivity, Diffusion Coefficients, and Degree of Dissociation in Lithium
      Electrolytes, Ionic Liquids, and Hydrogel Polyelectrolytes.
AB  - The conductive and diffusional behavior of electrolytes in media with different
      dielectric and viscoelastic properties is investigated. A revised model to
      separate the contribution of dissociated and nondissociated species to the
      diffusion coefficients determined with NMR is proposed. Impedance spectroscopy is
      used to measure the ionic conductivity of lithium salts in aqueous medium, ionic
      liquids in aprotic solvents, and hydrogel polyelectrolytes. The diffusion
      coefficients of the species of interest in those systems are determined with
      multinuclear pulsed-gradient spin-echo (PGSE) NMR. The results are analyzed using
      the revised model. It is shown that the degree of ionization could be determined
      directly from measurements of ionic conductivity and diffusion coefficients in
      very different types of electrolytes and in a wide range of concentrations.
      Furthermore, these findings support the original Arrhenius hypothesis about
      electrolytes and show that the assumption of a complete dissociation is not
      required to describe their conductive behavior. The reduced conductivity observed
      in hydrogels, at or near swelling equilibrium, compared to that in solutions
      could be attributed mainly to the hindered ionic mobility caused by the network
      structure.

PMID- 30092638
TI  - Fast IR-Actuated Shape-Memory Polymers Using in Situ Silver Nanoparticle-Grafted
      Cellulose Nanocrystals.
AB  - In recent years, shape-memory polymers (SMPs) have gained a key position in the
      realm of actuating applications from daily life products to biomedical and
      aeronautic devices. Most of these SMPs rely mainly on shape changes upon direct
      heat exposure or after stimulus conversion (e.g., magnetic field and light) to
      heat, but this concept remains significantly limited when both remote control and
      fine actuation are demanded. In the present study, we propose to design plasmonic
      silver nanoparticles (AgNPs) grafted onto cellulose nanocrystals (CNCs) as an
      efficient plasmonic system for fast and remote actuation. Such CNC- g-AgNPs
      "nanorod-like" structures thereby allowed for a long-distance and strong coupling
      plasmonic effect between the AgNPs along the CNC axis, thus ensuring a fast
      photothermal shape-recovery effect upon IR light illumination. To demonstrate the
      fast and remote actuation promoted by these structures, we incorporated them at
      low loading (1 wt %) into poly(epsilon-caprolactone) (PCL)-based networks with
      shape-memory properties. These polymer matrix networks were practically designed
      from biocompatible PCL oligomers end-functionalized with maleimide and furan
      moieties in the melt on the basis of thermoreversible Diels-Alder reactions. The
      as-produced materials could find application in the realm of soft robotics for
      remote object transportation or as smart biomaterials such as self-tightening
      knots with antibacterial properties related to the presence of the AgNPs.

PMID- 30092639
TI  - Naringin Activates AMPK Resulting in Altered Expression of SREBPs, PCSK9, and
      LDLR To Reduce Body Weight in Obese C57BL/6J Mice.
AB  - Previous investigations have shown molecular cross-talk among activated adenosine
      monophosphate-activated protein kinase (AMPK), proprotein convertase
      subtilisin/kexin type 9 (PCSK9), sterol regulatory element-binding proteins
      (SREBPs), and low-density lipoprotein receptor (LDLR) and that it may be an
      innovative pharmacologic objective for treating obesity. We scrutinized the
      beneficial effect of naringin, a flavanone-7- O-glycoside, on obesity and the
      mechanisms in the present study. We arbitrarily divided 50 mice into five groups
      ( n = 10): 25 or 50 or 100 mg/kg/day naringin-treated obese mice (gavage for 8
      weeks), untreated obese mice, and C57BL/6J control. After 8 weeks, body weight
      was 51.8 +/- 4.4 in the untreated obese mice group, while the weights were 41.4
      +/- 4.1, 34.6 +/- 2.2, and 28.0 +/- 2.3 in 25, 50,100 mg/kg naringin groups,
      respectively. Moreover, naringin treatment significantly decreased plasma 8
      isoprostane (an indicator of the oxidative stress) level, fat weight, liver
      weight, hepatic total cholesterol concentration, hepatic triglyceride
      concentration, plasma leptin level, plasma insulin content, plasma low-density
      lipoprotein cholesterol level, and plasma PCSK9 production concomitantly with
      down-regulated expression of SREBP-2, PCSK9, and SREBP-1, and up-regulated
      expression of p-AMPKalpha and LDLR. The present results suggest that naringin
      activates AMPK resulting in altered expression of SREBPs, PCSK9, and LDLR to
      reduce the body weight of obese C57BL/6J mice.

PMID- 30092640
TI  - Design and Discovery of Novel Chiral Antifungal Amides with 2-(2
      Oxazolinyl)aniline as a Promising Pharmacophore.
AB  - Inspired by established succinate dehydrogenase inhibitors (SDHIs), our
      continuing efforts toward the discovery of chiral antifungal amides turned to the
      optimization of their polar regions with 2-(2-oxazolinyl)aniline as a known
      pharmacophore. Scaffold hopping and bioactivity-guided convergent synthesis
      enabled the identification of promising antifungal categories. Fine tuning of the
      substituents and chirality furnished seven amides (1s, 1t, 2d, 2h, 2j, 3k, and
      2l) as antifungal candidates, with EC50 values lower than 5 mg/L. The first
      investigation of chiral amides of acyclic acids as SDHIs was conducted, and
      compound 2d was selected as a promising candidate against Botrytis cinerea, with
      a preventative efficacy of up to 93.9% at 50 mg/L, which is better than that of
      boscalid. The different binding models between compounds with different
      configurations were simulated for compound 2d and its diastereoisomers. The
      benefits of synthetic accessibility and cost-effectiveness highlight the
      practical potential for compound 2d as a good alternative to known SDHI
      fungicides.

PMID- 30092641
TI  - Total Structure Determination of Au16(S-Adm)12 and Cd1Au14(S tBu)12 and
      Implications for the Structure of Au15(SR)13.
AB  - Ultrasmall nanoclusters (e.g., Au15(SR)13) are crucial in not only real
      applications such as bioapplication but also in understanding the structure
      transition from gold complexes to gold nanoclusters. However, the determination
      of these transition-sized gold nanoclusters has long been a major challenge. In
      this work, two new nanoclusters in the transition regime, including the thus far
      smallest thiolated alloy nanocluster Cd1Au14(S tBu)12 and the homogold
      nanocluster Au16(S-Adm)12, are obtained and their atomic structures are fully
      determined by single crystal X-ray diffraction. Moreover, based on the structures
      of Cd1Au14(SR)12 and Au16(SR)12, we perform DFT calculations to predict the
      structure of the "transformation" nanocluster, Au15 (Au15(SR)12- and Au15(SR)13).
      Overall, this work bridges the gaps between gold complexes and nanoclusters.

PMID- 30092642
TI  - Kinetics of the Reaction of the Cyclopentadienyl Radical with Nitrogen Dioxide.
AB  - The kinetics of the reaction of the cyclopentadienyl radical (c-C5H5) with
      nitrogen dioxide (NO2) was studied by laser photolysis/photoionization mass
      spectroscopy. Overall rate constants were obtained in direct real-time
      experiments in the temperature region 305-800 K and at bath gas densities of (3.0
      12.0) * 1016 molecules cm-3. The overall rate constant is independent of
      temperature between 300 and 400 K but decreases by a factor of approximately 7
      above 400 K, without any discernible pressure dependence. A potential energy
      surface study of the reaction was performed, and an RRKM/master equation model
      was created. The reaction proceeds via initial addition to one of the two types
      of atoms of the NO2 molecule (nitrogen or oxygen). The N-bonded adduct can
      isomerize and decompose back to the reactants; this channel is significantly
      affected by falloff above 400 K and, although dominant at room temperature,
      becomes negligible at 600 K and above. The O-bonded adduct undergoes chemically
      activated isomerizations and decomposition, with a minor contribution from
      stabilization at low temperatures; this channel dominates at high temperatures
      and is effectively pressure-independent. The model provides a quantitative
      explanation for the observed temperature dependence of the rate constant.

PMID- 30092643
TI  - Fluorescence of 4-(Diisopropylamino)benzonitrile (DIABN) Single Crystals from 300
      K down to 5 K. Intramolecular Charge Transfer Disappears below 60 K.
AB  - Single crystals of 4-(diisopropylamino)benzonitrile (DIABN) undergo an
      intramolecular charge transfer (ICT) reaction in the excited singlet state. At
      300 K, the fluorescence consists of emissions from the locally excited (LE) and
      from the ICT state. Upon cooling to 5 K, the ICT fluorescence intensity gradually
      decreases relative to that of the LE emission and is absent below 60 K. With
      crystalline 4-(dimethylamino)benzonitrile (DMABN), in contrast, only LE emission
      is found over the entire range from 300 to 5 K. The phosphorescence spectra of
      the DIABN and the DMABN crystals do not present any evidence for an additional
      ICT emission, showing that ICT does not occur in the triplet state. An activation
      energy Ea of ~4 kJ/mol is determined for the LE -> ICT reaction of DIABN
      crystals, from the temperature dependence of the fluorescence decay times tau2
      and tau1. Ea is attributed to changes in the molecular conformation of DIABN
      other than a full rotation of the large diisopropylamino group with respect to
      the benzonitrile moiety. In a comparison with crystal and solution data,
      literature results from transient vibrational and absorption spectra are
      discussed and it is concluded that they cannot be employed to favor the TICT
      (perpendicular twist) over the PICT (planar) model for DIABN and DMABN.

PMID- 30092644
TI  - Outstanding Resistance of H2S-Modified Cu/TiO2 to SO2 for Capturing Gaseous Hg0
      from Nonferrous Metal Smelting Flue Gas: Performance and Reaction Mechanism.
AB  - The utilization of H2SO4, produced using SO2 from nonferrous metal smelting flue
      gas as a source of S, is extremely restricted due to Hg contamination; therefore,
      there is great demand to remove Hg0 from smelting flue gas. Although the ability
      of Cu/TiO2 to capture Hg0 is excellent, its resistance to H2O and SO2 is very
      poor. In this study, Cu/TiO2 was treated with H2S to improve its resistance to
      H2O and SO2 for capturing Hg0. The chemical adsorption of Hg0 on Cu/TiO2 was
      primarily through the HgO route, which was almost suppressed by H2O and SO2 due
      to the transformation of CuO into CuSO4. Besides the HgO route, the HgS route
      also contributed to the chemical adsorption of Hg0 on modified Cu/TiO2. As the
      CuS on modified Cu/TiO2 was inert to H2O and SO2, the chemical adsorption of Hg0
      on modified Cu/TiO2 through the HgS route was barely inhibited. Meanwhile, the
      HgS route was predominant in the chemical adsorption of Hg0 on modified Cu/TiO2.
      Therefore, modified Cu/TiO2 exhibited an excellent resistance to H2O and SO2, and
      its Hg0 capture capacity from simulated flue gas was up to 12.7 mg g-1 at 100 
      degrees C.

PMID- 30092645
TI  - Tunability of liquid-infused silicone materials for biointerfaces.
AB  - The ability to control the properties of bio-inspired liquid-infused surfaces is
      of interest in a wide range of applications. Liquid layers created using oil
      infused polydimethylsiloxane elastomers offer a potentially simple way of
      accomplishing this goal through the adjustment of parameters such as curing agent
      ratio and oil viscosity. In this work, the effect of tuning these compositional
      parameters on the properties of the infused polymer are investigated, including
      infusion dynamics, stiffness, longevity in the face of continuous liquid
      overlayer removal, and resistance to bacterial adhesion. It is found that that
      curing agent concentration appears to have the greatest impact on the
      functionality of the system, with a lower base-to-curing agent ratio resulting in
      both increased longevity and improved resistance to adhesion by Escherichia coli.
      A demonstration of how these findings may be implemented to introduce patterned
      wettability to the surface of the infused polymers is presented by controlling
      the spatial arrangement of bacteria. These results demonstrate a new degree of
      control over immobilized liquid layers and will facilitate their use in future
      applications.

PMID- 30092646
TI  - Perceived Synergistic Risk for Lung Cancer After Environmental Report-Back Study
      on Home Exposure to Tobacco Smoke and Radon.
AB  - PURPOSE: To examine the short-term impact of a personalized environmental report
      back intervention to reduce home exposure to tobacco smoke and radon on
      perception of synergistic risk for lung cancer. Radon-induced lung cancer is more
      common among those exposed to tobacco smoke. DESIGN: Randomized controlled trial.
      SETTING: Primary care clinics and a pharmacy waiting area at a University Medical
      Center in the Southeastern United States and community events. PARTICIPANTS: Five
      hundred sixty adult homeowners and renters (3-month follow-up, n = 334).
      INTERVENTION: Personalized environmental report back. MEASURES: Single-item
      synergistic risk perception measure using 5-point Likert-type scale. ANALYSIS:
      Change in synergistic risk from baseline to 3 months was evaluated using a
      generalized estimating equation model containing main effects of treatment group
      and time. Covariates in the model included age, gender, education, and home
      smoking status. RESULTS: For treatment and control groups combined, there was a
      significant increase in perception of synergistic risk from baseline to 3 months,
      but the study groups did not differ. There was no association between perceived
      synergistic risk and whether or not there were smokers at home. CONCLUSION:
      Learning about combined risks for lung cancer, with or without dual home
      screening for secondhand smoke and radon and environmental report-back, may
      enhance perceived risk for combined environmental exposures. Evaluation of
      perceived synergistic risk with a single item is a study limitation.

PMID- 30092647
TI  - Reply to Letter by Akboga et al Entitled "Are Endocan and Ischemia-Modified
      Albumin Reliable Biomarkers for Endothelial Dysfunction in Type 2 Diabetes
      Mellitus?"

PMID- 30092648
TI  - Neuronal injuries evidenced by transient cortical magnetic resonance enhancement
      in hemiplegic migraine: A case report.
AB  - Background Magnetic resonance imaging abnormalities in hemiplegic migraine have
      been described previously but were limited to a cortical thickening and biphasic
      alternation of hypoperfusion and hyperperfusion. Our report reveals possible
      blood-brain barrier disruption during migraine. Case We present the first
      demonstrated case of regressive diffuse hemispheric cortical enhancement in
      sporadic hemiplegic migraine, with histological correlation revealing neuronal
      lesions similar to ischemic lesions. This is probably due to the severity of the
      attack as indicated by the left hemiplegia and transient altered consciousness in
      our 43-year-old male patient. Conclusion Cortical contrast enhancement on 3D T1
      images may suggest migraine severity and be predictive of neuronal loss.

PMID- 30092649
TI  - Corneal epithelial stem cells for corneal injury.
AB  - INTRODUCTION: Ocular surface diseases with limbal insufficiency represent a
      therapeutic challenge for restoring vision. This corneal deficiency includes both
      classical ocular diseases (as chemical burns) and rare ocular diseases (as
      congenital aniridia and ocular cicatricial pemphigoid). Areas covered: Our
      understanding of limbal epithelial stem cells (LESCs) has increased the potential
      for treatment options. Pharmacological treatment strategies (as regenerating
      agent ophthalmic solutions) and especially surgical treatment strategies are
      available. Isolated LESCs can be produced by limbal primary cultures obtained
      from explants or cell suspensions. We review the latest cornea surgery
      techniques. Expert opinion: The adjunction of human limbal mesenchymal cells as a
      support for limbal stem cell primary cultures appears to be of great interest.
      Recently, human-induced pluripotent stem cells have allowed the generation of
      minicorneal organoids. This potential means of creating a three-dimensional
      cornea with in vitro maturation opens up important research areas for corneal
      regeneration therapy.

PMID- 30092650
TI  - Economy of Hand Motion During Cleft Palate Surgery Using a High-Fidelity Cleft
      Palate Simulator.
AB  - OBJECTIVE: The objectives of this study were to assess economy of hand motion of
      residents, fellows, and staff surgeons using a high-fidelity cleft palate
      simulator to (1) stratify performance for the purpose of simulator validation and
      (2) to estimate the learning curve. DESIGN: Two residents, 2 fellows, and 2 staff
      surgeons performed cleft palate surgery on a high-fidelity cleft palate simulator
      while their hand motion was tracked using an electromagnetic hand sensor. The
      time, number of hand movements, and path length of their hands were determined
      for 10 steps of the procedure. The magnitude of these metrics was compared among
      the 3 groups of participants and utilized to estimate the learning curve using
      curve-fitting analysis. RESULTS: The residents required the most time, number of
      hand movements, and path length to complete the procedure. Although the number of
      hand movements was closely matched between the fellows and staff, the overall
      total path length was shorter for the staff. Inverse curves were fit to the data
      to represent the learning curve and 25 and 113 simulation sessions are required
      to reach within 5% and 1% of the expert level, respectively. CONCLUSION: The
      simulator successfully stratified performance using economy of hand motion. Path
      length is better matched to previous level of experience compared to time or
      number of hand movements.

PMID- 30092652
TI  - Care of the adult woman with Turner syndrome.
AB  - Turner syndrome (TS) is the most common chromosomal abnormality in females,
      affecting up to 1/2000 live female births. TS is associated with partial or
      complete loss of the second X-chromosome in phenotypic females and is associated
      with increased morbidity and mortality. There are many challenges in providing
      optimal care for the adult TS women. This review highlights uncertainties that
      remain in hormone replacement therapy, bone health and cardiovascular
      optimization and discusses current management recommendations based on the
      recently published international guidelines and the experience at the TS clinic
      at Monash Health.

PMID- 30092651
TI  - Fifteen-degree clavicular hook plate achieves better clinical outcomes in the
      treatment of acromioclavicular joint dislocation.
AB  - OBJECTIVE: Clavicular hook plate application is one of the most commonly used
      treatment methods for acromioclavicular (AC) joint dislocation, although it may
      cause multiple postoperative complications. We modified the regularly used 0
      degrees  hook plate to 15 degrees  and compared the clinical outcomes of these
      two hook plates for treatment of AC joint dislocation. METHODS: Forty-three
      patients with acute AC joint dislocation were randomly enrolled (0 degrees  hook
      plate, 20 patients; 15 degrees  hook plate, 23 patients). The American Shoulder
      and Elbow Surgeons (ASES) and visual analog scale for pain (VASP) scores were
      evaluated preoperatively and at 3 days and 1, 2, 3, and 6 months postoperatively
      and compared between the two groups. RESULTS: Compared with the preoperative
      scores, the 6-month postoperative ASES score gradually increased but the VASP
      score decreased in both groups. Furthermore, the ASES and VASP scores were
      significantly different between the two groups at every postoperative time point.
      CONCLUSION: The 15 degrees  hook plate is superior to the 0 degrees  hook plate
      in reducing shoulder pain and improving postoperative recovery in the treatment
      of AC joint dislocation. LEVEL OF EVIDENCE: Level III; Treatment study
      (retrospective comparative study).

PMID- 30092654
TI  - Genome-wide characterization and expression profiling of diacylglycerol
      acyltransferase genes from maize.
AB  - Diacylglycerol acyltransferase (DGAT) catalyzes the only rate-limiting step in
      the pathway of plant oil (TAG) biosynthesis and is involved in plant development.
      In this study, five DGAT family members were identified from maize genome
      database. Phylogenetic analysis classified the ZmDGATs into type-I, II, and III
      clusters. Conserved functional domain analysis revealed that the proteins encoded
      by ZmDGAT1 contained conserved MBOAT domains, while two ZmDGAT2-encoding proteins
      harbored LPLAT domains. qRT-PCR analysis showed that ZmDGAT genes exhibited very
      high relative expression in developing seeds, especially at the early stage of
      seed development. Under various abiotic stress conditions, differential responses
      of ZmDGAT genes were observed. An overall significant induction of ZmDGAT genes
      under cold stress in leaves and a quick and strong response to osmotic stresses
      in roots were highlighted. This study provides useful information for
      understanding the roles of DGATs in oil accumulation and stress responses in
      higher plants.

PMID- 30092653
TI  - Development and Acceptability of Locally Made Fish-Based, Ready-to-Use Products
      for the Prevention and Treatment of Malnutrition in Cambodia.
AB  - BACKGROUND: Cambodia has a high prevalence of moderate acute malnutrition and
      severe acute malnutrition (SAM). The SAM treatment requires ready-to-use
      therapeutic foods (RUTFs), whereas ready-to-use supplementary foods (RUSFs) are
      used for prevention of acute malnutrition. Three locally produced fish-based
      products were developed: an RUTF paste (NumTrey-Paste) for treatment and 2 wafer
      versions, one for prevention (NumTrey-RUSF) and one for treatment (NumTrey-RUTF).
      OBJECTIVE: To assess the acceptability of NumTrey-Paste and NumTrey-RUSF in
      comparison to a standard biscuit product (BP-100) used for the treatment of SAM.
      METHODS: Acceptability of NumTrey-RUSF and NumTrey-Paste was tested in a
      nonblinded crossover taste trial among children (n = 52), aged >= 6 months to 18
      years, and their caregivers. Eight organoleptic qualities were assessed on a 5
      point hedonic scale, as well as a ranking test. A score of 1 to 3 was categorized
      as acceptable. The acceptability of NumTrey-RUTF was assessed using the
      caregivers' perception during an SAM treatment intervention. RESULTS: Taste
      trial: The proportion of children categorizing products as overall acceptable was
      lowest for NumTrey-Paste compared to for BP-100 and NumTrey-RUSF (21% vs 43% [BP
      100] and 36% [NumTrey-RUSF]). No difference was found in the proportion of
      children who ranked BP-100 or NumTrey-RUSF as "liked most" ( P > .05).
      Acceptability of NumTrey-RUSF ranked highest in appearance and taste (caregiver),
      whereas acceptability of NumTrey-Paste was ranked lowest in appearance and smell
      among the products. Intervention trial: The acceptability of NumTrey-RUTF
      increased from 72% to 86%. CONCLUSIONS: The overall acceptability was ranked
      lowest for a pure paste product. However, filling the paste into a wafer made the
      product more acceptable.

PMID- 30092655
TI  - Utility of the JT Peak Interval and the JT Area in Determining the Proarrhythmic
      Potential of QT-Shortening Agents.
AB  - Drug-induced long QT increases the risk of ventricular tachyarrhythmia known as
      torsades de pointes (TdP). Many biomarkers have been used to predict TdP. At
      present, however, there are few biomarkers for arrhythmias induced by QT
      shortening drugs. The objective of the present study was to identify the best
      biomarkers for predicting arrhythmias caused by the 4 potassium channel openers
      ICA-105574, NS-1643, R-L3, and pinacidil. Our results showed that, at higher
      concentrations, all 4 potassium channel openers induced ventricular tachycardia
      (VT) and ventricular fibrillation (VF) in Langendorff-perfused guinea pig hearts,
      but not in rabbit hearts. The electrocardiography parameters were measured
      including QT/QTc, JT peak, Tp-e interval, JT area, short-term beat-to-beat QT
      interval variability (STV), and index of cardiac electrophysiological balance
      (iCEB). We found that the potassium channel openers at test concentrations
      shortened the QT/QTc and the JT peak interval and increased the JT area.
      Nevertheless, even at proarrhythmic concentrations, they did not always change
      STV, Tp-e, or iCEB. Receiver operating characteristic curve analysis showed that
      the JT peak interval representing the early repolarization phase and the JT area
      reflecting the dispersion of ventricular repolarization were the best predictors
      of VT/VF. Action potential recordings in guinea pig papillary muscle revealed
      that except for pinacidil, the potassium channel openers shortened APD30 in a
      concentration-dependent manner. They also evoked early or delayed
      afterdepolarizations at fast pacing rates. Patch-clamp recordings in guinea pig
      ventricular cardiomyocytes showed that the potassium channel openers enhanced the
      total outward currents during the early phase of action potential repolarization,
      especially at proarrhythmic concentrations. We concluded that the JT peak
      interval and the JT area are surrogate biomarkers identifying the risk of
      proarrhythmia associated with the administration of QT-shortening agents. The
      acceleration of early-phase repolarization and the increased dispersion of
      ventricular repolarization may contribute to the occurrence of arrhythmias.

PMID- 30092656
TI  - Characterization of the GATA gene family in Vitis vinifera: genome-wide analysis,
      expression profiles, and involvement in light and phytohormone response.
AB  - The plant GATA family is one of the most important transcription factors involved
      in light-responsive development, nitrogen metabolism, phytohormone signaling, and
      source/sink balance. However, the function of the GATA gene is less known in
      grape (Vitis vinifera L.). In this study, we comprehensively analyzed the GATA
      family in grape, particularly the phylogenetic evolution, duplication patterns,
      conserved motifs, gene structures, cis-elements, tissue expression patterns, and
      predicted function of VvGATA genes in response to abiotic stress. The potential
      roles of VvGATA genes in berry development were also investigated. The GATA
      transcription factors displayed expression diversity among different grape organs
      and tissues, and some of them showed preferential expression in a specific
      tissue. Heterotrophic cultured cells were used as model systems for the
      functional characterization of the VvGATA gene and study of its response to light
      and phytohormone. Results indicated that some VvGATA genes displayed differential
      responses to light and phytohormones, suggesting their role in light and hormone
      signaling pathways. A thorough analysis of GATA transcription factors in grape
      (V. vinifera L.) presented the characterization and functional prediction of
      VvGATA genes. The data presented here lay the foundation for further functional
      studies of grape GATA transcription factors.

PMID- 30092657
TI  - 'Make the Connection' parenting skills programme: a controlled trial of
      associated improvement in maternal attitudes.
AB  - OBJECTIVE: Assess the effectiveness of Make the Connection (MTC), an attachment
      focused parenting programme, in fostering maternal attitudes thought to underlie
      sensitive responding. BACKGROUND: Effective parenting programmes are likely to
      mitigate negative outcomes associated with insecure attachment in infancy.
      Negative maternal attitudes and cognitions are thought to underlie insensitive
      parenting behaviour, and thus constitute a promising target for intervention.
      METHODS: 180 mothers of young infants were assigned to experimental or waitlist
      control groups based on programme availability. Mothers completed questionnaires
      assessing parental attitudes at baseline, and again either after participating in
      MTC or after a 9-week waitlist period. RESULTS: Participants who completed MTC
      showed significant improvement in overall attitude with a medium effect size
      relative to the waitlist control group, which showed no change. A small but
      significant interaction with infant age was noted, such that mothers of younger
      infants showed slightly more attitude improvement. Relative to the control group,
      participation in Make the Connection was associated with significant improvement
      in all attitudes except for self-efficacy as a parent, which improved with time
      regardless of programme participation. CONCLUSION: Make the Connection is
      effective in promoting positive parent-to-infant attachment and is a strong
      candidate for public health initiatives targeting parenting skills.

PMID- 30092658
TI  - Approaches to Direct Oral Anticoagulant Selection in Practice.
AB  - Direct oral anticoagulants (DOACs) carry many advantages over warfarin and are
      now considered first line or an alternative for mnay thromboembolic disorders.
      With the emergence of 5 DOAC agents to the market as well as the accumulating
      evidence gathered from head-to-head comparisons between the agents, we attempt to
      provide direction for clinicians when selecting the most appropriate DOAC agent.
      Important aspects such as efficacy, safety, cost effectiveness, approved
      indications, and other drug-related factors will be addressed to highlight the
      major similarities and diversities among the DOACs. When considering the safety
      profile of DOACs, evidence points toward apixaban as the safest followed by
      dabigatran and then rivaroxaban. On the other hand, dabigatran currently has the
      only approved antidote, idarucizumab. According to the approved DOAC indications,
      rivaroxaban may be favorable in European countries given its additional
      indication for secondary prevention of myocardial infarction. Following
      rivaroxaban, dabigatran and apixaban have the largest number of approved
      indications and lastly comes edoxaban and then betrixaban. For patients with
      renal impairment, betrixaban is the safest option, followed by apixaban and
      edoxaban, then rivaroxaban and lastly dabigatran. When considering DOAC dosing,
      rivaroxaban, edoxaban, and betrixaban are mainly dosed once daily compared to
      dabigatran and apixaban, which are dosed twice daily. However, rivaroxaban and
      betrixaban must be administered with food, which adds another level of complexity
      to the DOAC dosing. Lastly, taking into consideration drug interactions,
      dabigatran, edoxaban, and betrixaban have the least amount of interactions
      compared to apixaban and rivaroxaban. Each DOAC has its own set of features that
      makes it better suited than others based on the exact clinical situation.
      Therefore, no conclusion can be drawn to the most superior DOAC based on the
      aspects discussed in this review.

PMID- 30092659
TI  - Cardiac rehabilitation and its effects on cognition in patients with coronary
      artery disease and heart failure.
AB  - INTRODUCTION: Cardiac rehabilitation program is an evidence-based intervention
      and established model of exercise delivery following myocardial infarction and
      heart failure. Although it forms an important part of recovery and helps to
      prevent future events and complications, there has been little focus on its
      potential cognitive benefits. Areas covered: Coronary artery disease and heart
      failure are common heart problems associated with significant morbidity and
      mortality, and cognitive decline is commonly seen in affected individuals.
      Cognitive impairment may influence patient self-management by reducing medication
      adherence, rendering patients unable to make lifestyle modifications and causing
      missed healthcare visits. Cognitive assessment in cardiac rehabilitation as an
      outcome measure has the potential to improve clinical, functional and behavioral
      domains as well as help to reduce gaps in the quality of care in these patients.
      Expert commentary: Limited evidence at present has shown that cardiac
      rehabilitation and exercise has potential in preventing cognitive decline.
      Cardiac prehabilitation, a rehabilitation-like program delivered before cardiac
      surgery, may also play a role in preventing postoperative cognitive dysfunction,
      but needs future research studies to support it.

PMID- 30092660
TI  - Shields and garb for decreasing radiation exposure in the cath lab.
AB  - INTRODUCTION: Decreasing radiation exposure of the cardiac catheterization
      laboratory staff is critical for minimizing radiation-related adverse outcomes
      and can be accomplished by decreasing patient dose and by shielding. Areas
      covered: protection from ionizing radiation can be achieved with architectural,
      equipment-mounted, and disposable shields, as well as with personal protective
      equipment. Expert commentary: Radiation protective aprons are the most commonly
      used personal protective equipment and provide robust radiation protection but
      can cause musculoskeletal strain. Use of a thyroid collar is recommended, as is
      use of 'shin guards', lead glasses and radioprotective caps, although the
      efficacy of the latter is being debated. Alternatives to lead aprons include
      shielding suspended from the ceiling and robotic percutaneous coronary
      intervention. Radiation protective gloves and cream can be used to protect the
      hands, but the best protection is to not directly expose them to the radiation
      beam. Devices that provide real time operator radiation dose monitoring can
      enable real time adjustments in positioning and shield placement, reducing
      radiation dose. Shielding can be achieved with architectural, equipment-mounted,
      and disposable shields. Equipment-mounted shielding includes ceiling-suspended
      shields, table-suspended drapes, and radioabsorbent drapes. Personal protective
      equipment and shielding should be consistently and judiciously utilized by all
      catheterization laboratory personnel.

PMID- 30092661
TI  - Parent Observations of the Health Status of Infants With Clefts of the Lip:
      Results From Qualitative Interviews.
AB  - OBJECTIVE: To explore, using semistructured qualitative interviews, parent
      observations of their infant's health as they relate to having a cleft lip or
      cleft lip and cleft palate (CL+/-P) and/or associated treatments. DESIGN: Cross
      sectional, qualitative study across 3 sites. SETTING: Parents were recruited from
      3 academic craniofacial centers. Most interviews were conducted over the
      telephone, audio-recorded, and transcribed. PARTICIPANTS: Forty-one parents (31
      English-, 10 Spanish-speaking) were interviewed. Parents had a child ages 1 to 35
      months diagnosed with CL+/-P. MAIN OUTCOME MEASURE(S): Twelve domains reflecting
      infant health and well-being, likely affected by a CL+/-P and/or associated
      treatments, were identified from clinical experience and literature review. Study
      investigators conducted semistructured interviews based on 12 identified domains.
      After transcripts of the interviews were reviewed, our multidisciplinary team
      selected illustrative quotes from each domain that reflected consistent
      observations made by parents. RESULTS: Parents' responses covered all 12 domains.
      Specifically, parents discussed the domain of feeding most frequently, followed
      by observations about sleep, development, comfort, breathing, and vocalization.
      CONCLUSIONS: We found that parents of infants with clefts provided caregiver
      centered language useful in describing their daily observations. No additional
      domains of infant health were noted by parents. We will use these observations
      and language to develop and validate a parent-reported observation diary that can
      augment assessments of the impacts of interventions on infants who are receiving
      care for CL+/-P.

PMID- 30092662
TI  - Prevalence and relevant factors of anxiety and depression among pregnant women in
      a cohort study from south-east China.
AB  - OBJECTIVE: To describe the prevalence rate of prenatal anxiety and depression
      among pregnant women in a prospective cohort study and to explore the relevant
      factors of anxiety and depression during each trimester. METHODS: Pregnant women
      were recruited into the Zhoushan Pregnant Women Cohort at Zhoushan Maternal and
      Child Care Hospital from September 2011 to March 2015. A self-made questionnaire
      was used to collect information about social demography, reproductive history,
      physical activity, and life behaviour at the first, second and third trimester,
      respectively. The Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression
      Scale (SDS) were used to assess anxiety and depression status at each trimester,
      respectively. Prevalence rates of prenatal anxiety and depression at each
      trimester were described. RESULTS: The prevalence of anxiety status was 22.7%,
      17.4% and 20.8% in the first, second and third trimester, respectively. The
      corresponding prevalence rate of depression status was 35.7%, 24.0% and 26.1%,
      respectively. Furthermore, women with a lower education level (junior high school
      or below) and a more physical occupation had higher prevalence of anxiety and
      depression status. CONCLUSIONS: The prevalence of prenatal anxiety and depression
      status was very common during pregnancy among pregnant women. Lower educational
      level and more physical occupations were associated with higher prevalence of
      anxiety and depression status.

PMID- 30092663
TI  - Lactobacillus plantarum IS-10506 probiotic administration increases amlodipine
      absorption in a rabbit model.
AB  - Objective Probiotics are beneficial in human health. In this study, we
      investigated the effect of probiotics on absorption of amlodipine, a
      dihydropyridine calcium antagonist used in the treatment of angina and
      hypertension, in a rabbit model. Methods Lactobacillus plantarum IS-10506
      probiotic was administered for 14 days to male New Zealand rabbits. Blood samples
      were collected before and after probiotic supplementation. Amlodipine (10 mg) was
      then administered to all groups. Blood samples from a marginal vein were
      withdrawn at 5, 15, 30, 60, and 120 minutes to determine amlodipine
      concentrations in rabbit plasma. Results Amlodipine concentrations in the L.
      plantarum IS-10506 group were 4.95 +/- 1.22, 8.71 +/- 0.69, and 12.48 +/- 2.53
      ng/ml, and those in the control group were 1.69 +/- 0.31, 3.89 +/- 1.23, and 7.17
      +/- 1.85 ng/ml at 30, 60, and 120 minutes, respectively after administration of
      amlodipine. Amlodipine concentrations in the L. plantarum IS-10506 group were
      significantly higher than those in the control group at 30, 60, and 120 minutes
      after amlodipine administration. Conclusion Our results suggested that
      supplementation of L. plantarum IS-10506 significantly increases amlodipine
      plasma concentrations in rabbits.

PMID- 30092664
TI  - Seasonal variation of volatile oil composition and antioxidant property of aerial
      parts of Syzygium paniculatum Gaertn. grown in the Eastern Cape, South Africa.
AB  - Syzygium paniculatum Gaertn of the family Myrtaceae is a medicinal and aromatic
      plant. The hydrodistilled volatile oil (VO) from the aerial parts was
      characterised by GC-MS and Kovat's index, while the antioxidant property was
      investigated using spectrophotometric techniques. Antioxidant capacities of the
      aerial parts VOs range from 0.12 to 0.93 mg/mL in scavenging 2, 2-diphenyl-1
      picrylhydrazyl radicals (DPPH*). Overall, 75 and 67 compounds were identified
      from the summer and winter VOs, respectively. The main compounds were alpha
      pinene (33.13%), n-hexadecanoic acid (19.14%), limonene (14.26%), farnesol
      (14.21%), beta-ocimene (13.04%), citronellol (12.67%), linoleic acid (11.50%),
      octahydro-1,4-dimethyl azulene (11.57%), citral (9.91%), phytol (5.07%),
      linolenic acid (4.85%) and thymol (2.23%). The bioavailability of citronellol,
      thymol, beta-ocimene and linoleic acid, used as bactericidal, fungicidal and
      antioxidant agents in cosmetics and perfumery, suggests S. paniculatum potential
      as a natural food flavouring and source of antibiotics in this era of emerging
      multi-drug-resistant pathogens.

PMID- 30092665
TI  - Terezine E, bioactive prenylated tryptophan analogue from an endophyte of
      Centaurea stoebe.
AB  - Fungal endophytes are considered promising sources of new bioactive natural
      products. In this study, a Mucor sp. has been isolated as an endophyte from the
      medicinal plant Centaurea stoebe. Through bioactivity-guided fractionation, the
      isolation of the new bioactive terezine E in addition to the previously reported
      14-hydroxyterezine D was carried out. The isolated compounds were fully
      characterised by HRESIMS and 1D and 2D NMR analyses. Both compounds exhibited
      potent antiproliferative activity against K-562 and HUVEC cell lines and
      antifungal efficacy against the tested fungal strains.

PMID- 30092667
TI  - Should influenza vaccination be mandatory for healthcare workers?
AB  - Each year, many healthcare organizations deal with low influenza immunization
      rates among staff. Mandatory influenza vaccination programs may be considered in
      order to address this issue. These types of programs have caused controversy in
      the past, as staff has argued that they infringe upon their liberties and right
      to autonomy. However, if viewed from a public health perspective, mandatory
      vaccination programs are beneficial for both employees and patients and can be
      justified. When individuals make the decision to work in the medical field, it is
      assumed that their values align with those of the organization for which they
      work. This overrides their right to autonomy, since they are expected to put the
      safety of their patients ahead of their own personal interests. Although some may
      argue that receiving a flu shot is unsafe, evidence has demonstrated the
      opposite, and the minimal discomfort that may result from a vaccine is not enough
      to negate the responsibilities that healthcare workers have toward the patients
      they serve.

PMID- 30092666
TI  - Impact of CYP2A6 gene polymorphism on the pharmacokinetics of dexmedetomidine for
      premedication.
AB  - BACKGROUND: Dexmedetomidine is a widely used sedative in clinic, which is mainly
      metabolized by cytochrome P450 2A6 (CYP2A6). Dexmedetomidine was rarely reported
      for off-label usage of premedication, but lacking relevant pharmacokinetic
      investigations. Therefore, our study determined the dexmedetomidine
      pharmacokinetics of CYP2A6*4 allele in Chinese patients pretreated with
      dexmedetomidine whose mutation frequency of CYP2A6*4 are high, in order to
      provide clinical references. METHODS: Thirty-one elective surgery patients
      received premedication with 0.5 MUg/kg dexmedetomidine via intravenous pump.
      Their plasma concentrations at multiple time-points and polymorphism of CYP2A6*4
      were determined and statistically analyzed. RESULTS: 9 patients were *1/*4 or
      *4/*4, and 22 patients were *1/*1. The main pharmacokinetic parameters were area
      under curve (AUC) 1396.19 +/- 332.47h. ng. l-1, peak blood concentration (Cmax)
      495.50 +/- 104.90ng. l-1, distribution volume (V) 0.68 +/- 0.20 L/kg, clearance
      (CL) 0.38 +/- 0.11 L/h/kg, distribution half-life (t1/2alpha) 0.05 +/- 0.01h,
      elimination half-life (t1/2beta) 2.53 +/- 0.04h. No significant pharmacokinetic
      differences were found among CYP2A6*1/*1, *1/*4, and *4/*4 patients. CONCLUSIONS:
      In Chinese patients pretreated with dexmedetomidine, T1/2beta was consistent with
      that published, but T1/2alpha, V and Cl were lower. It was unnecessary to
      consider the mutation when developing the precision regimen of dexmedetomidine.

PMID- 30092668
TI  - Expression of CYP and GST in human normal and colon tumor tissues.
AB  - We investigated the immunohistochemical staining characteristics of cytochrome
      P450 1A1 (CYP1A1), CYPB1, CYP2E1, and glutathione S-transferase P1 (GSTP1),
      GSTT1, GSTO1, GSTK1 in colon tumor and surrounding normal colon tissues. Tissues
      were obtained from 47 patients with colon adenocarcinoma and the staining
      intensity of tumor and control tissues was compared. CYP1A1, CYP1B1, CYP2E1,
      GSTP1, GSTT1, GSTO1 and GSTK1 expressions in colon cancer cells were
      significantly greater than those in normal colon epithelial cells. No significant
      relation was found between the isoenzyme expressions and age, gender, smoking
      status, tumor grade and tumor stage. The higher expressions of CYP1A1, CYP1B1,
      CYP2E1, GSTP1, GSTO1, GSTT1 and GSTK1 in tumor than in normal colon tissues may
      be important for colon cancer progression and development.

PMID- 30092669
TI  - Characterization of drug-drug interactions in patients whose substance intake was
      objectively identified by detection in urine.
AB  - BACKGROUND: Identification of drug-drug interactions (DDIs) typically relies on
      patient medication lists which are prone to inaccuracies. This study describes
      use of a mass spectrometry test to detect recently ingested substances in urine
      with subsequent identification of DDIs. RESEARCH DESIGN AND METHODS: This was a
      retrospective analysis of the prevalence of DDIs identified in patients with
      chronic pain, addiction and/or behavioral health conditions in the U.S.
      Relationships between patient demographics, polypharmacy and the occurrence of
      DDIs were also described. RESULTS: Of 15,004 patients, 2964 (20%) had a DDI
      identified. There was a positive association between the number of substances
      detected in urine and the number of interactions identified (r = 0.5033, p-value
      = 0.0001). Of patients with polypharmacy, 15.6% had contraindicated or severe
      interactions identified compared to only 3.2% of those without polypharmacy. For
      polypharmacy patients, the youngest population studied had a much higher
      likelihood of having one or more DDIs identified compared to the other age groups
      (p-value = 0.0002). CONCLUSIONS: By utilizing a mass spectrometry test to
      objectively detect recently ingested substances followed by identification of
      DDIs, healthcare providers may be able to better characterize the true incidence
      of DDIs. Study findings may not be generalizable to healthcare populations
      outside of pain management, addiction treatment, and behavioral health.

PMID- 30092671
TI  - Progress on norovirus vaccine research: public health considerations and future
      directions.
AB  - INTRODUCTION: Noroviruses are the leading cause of foodborne illness worldwide,
      account for approximately one-fifth of acute gastroenteritis (AGE) cases
      globally, and cause a substantial economic burden. Candidate norovirus vaccines
      are in development, but there is currently no licensed vaccine. Areas covered:
      Noroviruses cause approximately 684 million cases and 212,000 deaths per year
      across all age groups, though burden estimates vary by study and region.
      Challenges to vaccine research include substantial and rapidly evolving genetic
      diversity, short-term and homotypic immunity to infection, and the absence of a
      single, well-established correlate of protection. Nonetheless, several norovirus
      vaccine candidates are currently in development, utilizing virus-like particles
      (VLPs), P particles, and recombinant adenoviruses. Of these, a bivalent
      GI.1/GII.4 VLP-based intramuscular vaccine (Phase IIb) and GI.1 oral vaccine
      (Phase I) are in clinical trials. Expert Commentary: A norovirus vaccine should
      target high-risk populations, including the young and the elderly, and protect
      them against the most common circulating norovirus strains. A norovirus vaccine
      would be a powerful tool in the prevention and control of norovirus while
      lessening the burden of AGE worldwide. However, more robust burden and cost
      estimates are needed to justify investments in and guide norovirus vaccine
      development.

PMID- 30092670
TI  - Establishing the usefulness of the GO-QOL in a UK hospital-treated population
      with thyroid eye disease in the CIRTED trial.
AB  - Thyroid eye disease (TED) is a potentially sight-threatening and cosmetically
      disfiguring condition arising in 25-50% of patients with Graves' hyperthyroidism.
      CIRTED is the first study to evaluate the long-term role of radiotherapy and
      prolonged immunosuppression with azathioprine in treating TED, one aim of which
      was to validate the use of the English version of GO-QOL in an UK population with
      TED. In a three stage design over a 48 week period, the GO-QOL was tested and
      compared to a general measure of quality of life (WHOQOL-Bref). In stage 1
      utilising a standard 14 day test-retest design both GO-QOL subscales achieved
      Cronbach's alphas demonstrating excellent validity and internal reliability
      (Visual Function 0.929 and 0.931; Appearance 0.888 and 0.906). In stage 2,
      Repeated Measures ANOVA demonstrated longitudinal validity, with both subscales
      of the GO-QOL showing significant change over time (Visual Function, eta2 =
      0.114, p < .001; Appearance, eta2 = 0.069, p < .002). In stage 3 the GO-QOL
      showed discriminant validity at the week 48 time point, with the visual function
      subscale being able to detect changes in groups identified by clinicians (using
      BCCOM ratings of improvement or deterioration), while both subscales could detect
      group differences when based on participants' subjective ratings of TED
      noticeability and severity. The results of this project provide support for the
      English translation of the GO-QOL as an outcome measure for patients with
      moderately severe active Graves' orbitopathy/TED.

PMID- 30092672
TI  - Advances in the genetics of acute lymphoblastic leukemia in adults and the
      potential clinical implications.
AB  - INTRODUCTION: Acute lymphoblastic leukemia (ALL) is a clonal disease of the
      hematopoietic system characterized by unique genetic characteristics. The
      significance of these genetic features has evolved over the past three decades.
      In the 1980s and 1990s, the primary interest was in excluding the Philadelphia
      chromosome; a finding more common in older adults which uniformly predicted for a
      rapidly fatal outcome. Areas covered: Over the past 15 years, much has evolved.
      Tyrosine kinase inhibitors completely changed the prognosis of Ph-positive ALL.
      In addition, the genetic characterization of Ph-negative ALL has significantly
      advanced through systematic progressive analyses of genetic data from large trial
      groups. These led to specific and more accurate prognostication, particularly at
      initial diagnosis. Expert commentary: These cytogenetic and molecular features
      will be reviewed in this paper and their ongoing significance will be critically
      analyzed in the era of minimal residual disease (MRD) determination, which has
      now superseded all the major known historic prognostic factors.

PMID- 30092673
TI  - Clinical significance of subcutaneous fat and fascial involvement in juvenile
      dermatomyositis.
AB  - OBJECTIVES: Subcutaneous involvement, including calcinosis and panniculitis, is a
      more common complication in juvenile dermatomyositis (JDM) than in adult
      dermatomyositis. Magnetic resonance imaging (MRI) is useful for evaluating
      disease distribution. We investigated the clinical significance of subcutaneous
      involvement in JDM. METHODS: Thighs and hips in 18 newly diagnosed JDM patients
      were evaluated with fat-suppression MRI. Bilateral muscle, fascial and
      subcutaneous fat involvement were scored from 0 to 8 points according to the
      severity of distribution on MRI. Associations between clinical manifestations,
      serum muscle enzymes, and MRI scores were also evaluated. RESULTS: Abnormal MRI
      findings in muscle, fascia and subcutaneous fat were observed in 18, 18, and 10
      patients, respectively. Subcutaneous fat scores were significantly higher in
      early-diagnosed JDM patients (diagnosed less than 2 months from onset) than in
      late-diagnosed JDM patients (diagnosed later) (p = .025). Serum aldolase was
      elevated in all patients, although only eight demonstrated elevated serum
      creatine phosphokinase. Serum aldolase was significantly correlated with MRI
      scores for subcutaneous fat (p < .0001, rho = .787) and fascia (p = .013 rho =
      0.574), but not muscle. Additionally, serum aldolase was significantly correlated
      with serum triglycerides (p = .009, rho = 0.629). CONCLUSION: Subcutaneous fat
      involvement is a characteristic finding in early-diagnosed JDM and correlates
      with elevated serum aldolase.

PMID- 30092674
TI  - Olaparib for the treatment of relapsed ovarian cancer with a BRCA1/2 mutation.
AB  - INTRODUCTION: Despite treatment strategies which include both surgery and
      chemotherapy, epithelial ovarian cancer often relapses and survival rates remain
      poor. There is therefore a need to identify novel treatment targets and develop
      approaches that improve outcomes. The role of both germ line and somatic
      mutations in BRCA1 and BRCA2 in the development of ovarian cancer is well
      established, with mutation in either gene resulting in deficiencies in homologous
      recombination. Olaparib is an orally active inhibitor of poly(ADP-ribose)
      polymerase (PARP) which has demonstrated anti-tumor activity in ovarian cancer.
      Areas covered: This review focuses on the rationale for olaparib therapy in the
      context of relapsed epithelial ovarian cancer associated with a BRCA1 or BRCA2
      mutation and summarizes the existing efficacy and safety data in this context.
      Ongoing phase III trials will be discussed. Expert commentary: Research regarding
      the optimal use of olaparib in the context of relapsed epithelial ovarian cancer
      associated with a BRCA mutation continues, with evidence for its use as
      maintenance therapy, treatment as a single agent and in combination with other
      targeted agents. The mechanisms of resistance require further exploration and it
      remains to be established whether retreatment or combination with other agents
      are viable treatment strategies.

PMID- 30092675
TI  - Effect of group leaders on doctors' learning in Balint groups.
AB  - Objective Although effective Balint leadership is viewed as essential for good
      Balint practice, nearly no quantitative research is available regarding the
      importance of the person of the group leader in Balint group outcome. This study
      aims to identify Balint group leaders' impact on "typical Balint" learning
      processes in Balint groups. Method A total of 1460 medical doctors in 352 Balint
      groups in Germany, Austria, and Switzerland were investigated. Based on the three
      learning dimensions of the Balint Group Session Questionnaire, statistical
      analyses were conducted to identify differential effectiveness in Balint
      leadership. Results On the basis of the mean scores of the Balint Group Session
      Questionnaire items across all group participants of each group leader, the 80
      certified Balint group leaders were clustered into two groups of more and less
      effective leaders by a hierarchichal cluster analysis. Mixed model analyses
      revealed that the effectiveness of the person of the Balint group leader was the
      most predictive factor for learning effects. Conclusions Training for Balint
      group leaders should take into account that effective learning processes in
      Balint groups are strongly related not only to the method itself but also to the
      person of the group leader.

PMID- 30092676
TI  - Personal characteristics associated with the effect of childhood trauma on
      health.
AB  - Objective This article will describe a pilot study to explore associations
      between adult attachment style, resilience, Adverse Childhood Experiences, and
      adult health. Method A self-report survey was mailed to 180 randomly selected
      primary care patients and linked to a retrospective chart review. The patients
      met the following criteria: (1) enrolled for at least the previous year at their
      primary care clinic, (2) 21 years of age or greater, (3) English as their primary
      language, and (4) were seen by their provider on selected dates of the study. The
      survey was made up of three instruments: (1) the Adverse Childhood Experiences
      Questionnaire which consists of 10 questions about the respondent's adverse
      experiences during their first 18 years of life; (2) the Relationship Scales
      Questionnaire which measures adult attachment style; and (3) the Connor-Davidson
      Resilience Scale, a self-report scale that measures individual's perceptions of
      their resilience. For each returned questionnaire, we calculated a measure of
      medical complexity using the Elixhauser Comorbidity Index. Results Of the 180
      randomly selected patients from four clinic sites, 84 (46.6%) returned completed
      questionnaires. We found that Adverse Childhood Experience scores were
      significantly correlated with health and attachment style and trended toward
      association with resilience. Conclusion This pilot study revealed expected
      relationships of the complex associations between Adverse Childhood Experiences,
      attachment style, and resiliency. Further research with more subjects is
      warranted in order to continue to explore these relationships.

PMID- 30092677
TI  - Patient-targeted googling and psychiatric professionals.
AB  - Objective This is a pilot study which assesses the beliefs of psychiatric
      professionals regarding obtaining patient information via the Internet as well as
      the frequency with which they do it in a variety of clinical settings. Methods
      Psychiatry faculty and residents were asked to participate in an anonymous online
      survey about their use of the search engine Google to find information about
      their patients. Data were analyzed with Microsoft Excel. Results The participants
      included 48 faculty and 34 residents (118 faculty and 44 residents were surveyed)
      with response rates of 41% and 77%, respectively. Majority of attending
      physicians and residents reported engaging in patient-targeted googling with no
      significant difference between the groups. Residents were most likely to search
      for patient information online in the psychiatric emergency room (45%).
      Psychiatric emergency room (36.8%) and private practice (31.6%) were notable
      clinical settings for obtaining further patient information on the Internet for
      the faculty. When describing reasons for engaging in patient-targeted googling,
      "patient care" was cited about twice as often as "curiosity" in the psychiatric
      emergency room, whereas "curiosity" and "patient care" were reasons mentioned in
      other clinical settings. In general, neither faculty nor residents report
      informing their patients of their Internet searches either before or after
      engaging in patient-targeted googling. Conclusion This study raises important
      questions about education for trainees and faculty regarding patient-targeted
      googling.

PMID- 30092679
TI  - Insight to the growing utilizations of high flow nasal oxygen therapy over non
      invasive ventilation in community teaching hospital: alternative or
      complementary?In response to: Mihaela S. Stefan, Patrick Eckert, Bogdan Tiru,
      Jennifer Friderici, Peter K. Lindenauer & Jay S. Steingrub (2018) High flow nasal
      oxygen therapy utilization: 7-year experience at a community teaching hospital,
      Hospital Practice, 46:2, 73-76, DOI: 10.1080/21548331.2018.1438739.

PMID- 30092678
TI  - Relationship between vasomotor symptoms and metabolic syndrome in postmenopausal
      women.
AB  - Objective This study was performed to compare the vasomotor symptoms and bone
      mineral density of postmenopausal women with and without metabolic syndrome.
      Methods We performed a cross-sectional study of 200 postmenopausal women
      attending routine health check-ups at Marmara Faculty of Medicine Pendik Training
      and Research Hospital from June 2015 to December 2015. The vasomotor symptoms
      scored were hot flashes and night sweats. Metabolic syndrome was defined using
      the consensus criteria of the International Diabetes Federation and the American
      Heart Association/National Heart, Lung, and Blood Institute. Results Women with
      vasomotor symptoms had no metabolic syndrome and were younger than those without
      vasomotor symptoms. There was no significant difference in vasomotor symptoms
      between patients with osteopenia in the femoral neck, total femur, and spine and
      patients with normal bone mineral density. The vasomotor symptoms were similar
      between smokers and nonsmokers. Conclusion The presence of metabolic symptoms is
      inversely associated with metabolic syndrome in postmenopausal women. Lipid
      abnormalities and a high body mass index may be important metabolic components
      associated with these symptoms. No relationship is present between vasomotor
      symptoms and the bone mineral density of the spine, femoral neck, and total
      femur.

PMID- 30092681
TI  - Understanding the implications of the biobehavioral basis of nicotine addiction
      and its impact on the efficacy of treatment.
AB  - INTRODUCTION: Tobacco use remains the leading cause of preventable death in the
      United States. There are efficacious behavioral and pharmacological options for
      smoking cessation including three FDA approved therapies - nicotine replacement
      therapy, varenicline and bupropion. Nevertheless, uptake of smoking cessation
      treatments continues to be poor and there is a need for novel smoking cessation
      treatments. Areas covered: This article reviews the biobehavioral basis of
      nicotine addiction, its implications for smoking cessation treatments, the
      various neurotransmitter systems involved in nicotine addictive effects, and
      their potential therapeutic value. Included are discussions around the role of
      genetic factors in predicting response to pharmacotherapy and what we know about
      appropriate application of pharmacotherapy and behavioral interventions for
      tobacco use disorder. The evidence for harm reduction measures in individuals who
      are not willing or able to quit smoking is also reviewed. Expert commentary: Many
      neurotransmitter system targets have been investigated as a result of our
      understanding of the underlying neurobiology of tobacco use disorder, and there
      remain important targets that have yet to be fully explored. rTMS or combination
      therapies are proposed as possible novel strategies to improve smoking cessation.

PMID- 30092680
TI  - The three-year efficacy of iguratimod in clinical daily practice in patients with
      rheumatoid arthritis.
AB  - OBJECTIVES: To assess the middle-term outcome of iguratimod (IGU) in rheumatoid
      arthritis (RA) patients. METHODS: Sixty-nine RA patients (14 males and 55
      females, mean age of 64.0 years) receiving IGU-containing therapies were
      enrolled. We divided these patients into three groups based on the treatment at
      the baseline: an IGU group, a Methotrexate (MTX) plus IGU group, and a biologics
      plus IGU group. The baseline characteristics and clinical course were evaluated
      over three years. Predictive factors associated with the achievement of low
      disease activity (LDA) were statistically analyzed. RESULTS: The survival rate of
      IGU therapy at 3 years was 40.6%. The disease activity was significantly
      decreased in the IGU group and MTX plus IGU group compared with the baseline.
      Furthermore, 38 patients (55.1%) were in remission or had LDA at 3 years. The
      patient gender, use of prednisolone (PSL) and DAS28-CRP at baseline were the
      factors associated with the achievement of remission or LDA at three years.
      CONCLUSIONS: IGU was effective without MTX or bDMARDs as well as in combination
      with MTX. A female gender, no use of PSL and a low DAS28-CRP at the initiation of
      IGU were associated with clinical remission or LDA achievement at three years.

PMID- 30092682
TI  - Current and future therapies for targeting HER2 mutations in gastrointestinal
      cancer.
AB  - INTRODUCTION: Gastrointestinal (GI) cancers altogether represent the most common
      cancer type. HER2 is found to be present in nearly all histologic types of GI
      cancers in variable degrees of expression. Over the last decade, substantial
      advances have been made in targeting HER2-positive cancers. Areas covered: The
      present review summarizes the current progress and future directions for HER2
      targeted therapies in GI cancers, including esophagogastric, pancreaticobiliary,
      and colon cancers. To date trastuzumab is the only anti-HER2 therapy approved for
      metastatic esophagogastric adenocarcinoma. Efforts are ongoing to expand the
      therapeutic role of HER2 to other GI cancers and overcome mechanisms of drug
      resistance. Novel agents and combinations are being tested in most HER2 positive
      GI cancers including early stage disease. These are of recent interest in
      colorectal cancer with studies indicating that HER2 overexpression might increase
      resistance to anti-EGFR therapy and may be potentially targeted. Expert
      commentary: With the current ability to sequence tumors and detect genetic
      alterations, emphasis should be put on genomically-selected pan-tumor targeted
      therapies. HER2 is a perfect example of a promising drug target in GI cancers.

PMID- 30092683
TI  - Impact of a pharmacist-driven pharmacovigilance system in a secondary hospital in
      the Gauteng Province of South Africa.
AB  - BACKGROUND AND AIMS: Under-reporting of adverse drug reactions (ADRs) by health
      care professionals (HCPs) is a worldwide problem. Spontaneous reporting in
      hospitals is scarce and several obstacles have been identified for this. Improved
      hospital-based reports could make important contributions to future care.
      Consequently, the objective of this study was to develop, implement and evaluate
      a structured pharmacist-driven pharmacovigilance (PV) system for in-patient ADR
      reporting in a leading public hospital in South Africa for future use in South
      Africa and wider. METHOD: Descriptive, operational intervention study with a pre
      post design. Pharmacist-driven interventions targeted at ADR reporting were
      implemented. Convenience sampling was used to recruit HCPs [medical
      practitioners, pharmacists, pharmacist assistants, and nurses] to complete a self
      administered questionnaire. The principal outcome measures were the number of the
      ADRs reported for inpatients, 18 months prior to and 18 months during the
      intervention period, as well as an evaluation of the intervention program in
      terms of continuous information and training. RESULTS: There was a significant
      increase in the number of HCPs reporting an ADR post-intervention (33.8% up from
      12.1%; p < 0.0001). Reasons for non-reporting decreased significantly, e.g. 'How,
      where and when to report' an ADR (p = 0.0027) and 'Concern that the report may be
      wrong' (p = 0.0041). HCPs' knowledge of the ADR reporting system also improved
      appreciably. This was apart from pharmacists who were already knowledgeable.
      CONCLUSION: The results showed the benefits of pharmacist-driven interventions on
      HCPs' knowledge and awareness of PV and the number of the ADRs reported. Hospital
      management and policy makers should consider the important role pharmacists can
      play in improving rational and safe use of medicines among inpatients, based on
      appropriate training of HCPs and proper systems. As a result, help achieve the
      standards established by the Department of Health in South Africa.

PMID- 30092684
TI  - Kinome analyses of inflammatory responses to swine barn dust extract in human
      bronchial epithelial and monocyte cell lines.
AB  - Exacerbated inflammation upon persistent barn organic dust exposure is a key
      contributor to the pathogenesis of lung inflammation and lung function decline.
      Barn dust constituents and the mechanisms contributing to the exacerbated
      inflammation are not clearly known. We set out to understand the inflammatory
      effects of Swine Barn Dust Extracts (SBDE) on human lung epithelial (BEAS2B) and
      macrophage (THP-1 monocyte derived) cell lines on a kinome array to determine
      phosphorylation events in the inflammatory signaling pathways. Upon identifying
      events unique to SBDE or those induced by innate immune ligands in each cell
      line, we validated the signaling pathway activation by transcriptional analyses
      of downstream inflammatory cytokines. Our findings indicate that SBDE-mediated
      pro-inflammatory effects are predominantly due to the induction of neutrophilic
      chemokine IL-8. Differentially phosphorylated peptides implicated in IL-8
      induction in BEAS2B cell line include, TLR2, 4, 5, 7, 8, 9, PKC, MAP kinases
      (p38, JNK), inflammasomes (NLRP1, NLRP3), NF-kappaB and AP-1. In the THP-1 cell
      line, in addition to the aforementioned peptides, peptides corresponding to RIG-I
      like receptors (RIG-I, MDA5) were found. This is the first report to demonstrate
      the application of a kinome array to delineate key inflammatory signaling
      pathways activated upon SBDE exposure in vitro.

PMID- 30092685
TI  - Alterations of microRNAs and their predicted targeting mRNAs expression in
      RAW264.7 macrophages infected with Omp25 mutant Brucella melitensis.
AB  - Brucellosis is a worldwide zoonosis caused by Brucella species and represents a
      serious threat to both human and animal health. Omp25 is an important immunogenic
      and protective antigen in Brucella species; however, the functional mechanism of
      Omp25 in macrophages has not yet been elucidated. Here, we constructed a Brucella
      melitensis omp25 deletion mutant (M5-90-Delta omp25) and performed microRNA
      (miRNA) profiling of infected RAW264.7 cells. Eight differentially expressed
      miRNAs ( mmu-miR-146a-5p, mmu-miR-155-5p, mmu-miR-3473a, mmu-miR-149-3p, mmu-miR
      671-5p, mmu-miR-1224-5p, mmu-miR-1895, and mmu-miR-5126) were identified, with
      quantitative real-time PCR (qRT-PCR) analysis confirming the up-regulation of mmu
      miR-146-a-5p and mmu-miR-155-5p and down-regulation of mmu-miR-149-3p and mmu-miR
      5126. mRNA profiling of B. melitensis M5-90-Deltao mp25-infected RAW264.7 cells
      identified 967 differentially expressed genes (DEGs) (fold change >= 2). Among
      these, we focused on genes that were predicted by TargetScan, miRanda, and PicTar
      to be the potential targets of the differentially expressed miRNAs. The results
      suggested that 17 separate genes are potentially targeted by mmu-miR-149-3p, with
      one of these genes, Tbr1, also targeted by mmu-miR-5126. qRT-PCR analysis
      confirmed the up-regulation of nine of the predicted target genes. Our findings
      provide important information about the functional molecules in host cells,
      including miRNA and their target genes, affected by Omp25 from Brucella. This
      information is particularly valuable for the prophylaxis and treatment of
      brucellosis.

PMID- 30092687
TI  - Preliminary Validation of the Rey 15-Item Test and Reliable Digit Span in Native
      Japanese Samples.
AB  - The Rey 15-Item Test and reliable digit span were evaluated in Japan.
      Participants were controls ( n = 15), healthy volunteers instructed to simulate
      memory impairment ( n = 12; 5 of 17 volunteers did not comply with instructions
      and were dropped), healthy elderly ( n = 12), and cognitively disabled nursing
      home residents ( n = 8). On the 15-Item Test, controls and elderly performed
      similarly and were combined. Nursing home residents could not cope with the 15
      Item Test and were dropped. Total score was a fair predictor of dissimulation
      using a cutoff <= 8. Rows were fair predictors using a <=2 cutoff. Sensitivities
      were low and specificities were excellent. Reliable digit span contrasts between
      simulators and each of the other groups demonstrated that reliable digit span
      discriminated controls and elderly from simulators (<=6 and <=5 cutoffs).
      Sensitivities were moderate and specificities were excellent. Reliable digit span
      did not differentiate simulators from nursing home residents.

PMID- 30092686
TI  - Inflammation on spinal magnetic resonance imaging is associated with poor bone
      quality in patients with ankylosing spondylitis.
AB  - OBJECTIVE: To determine the association between inflammatory lesions on spinal
      magnetic resonance imaging (MRI) and trabecular bone score (TBS) in patients with
      ankylosing spondylitis (AS). METHODS: Ninety-seven patients with AS underwent
      spine MRI and dual energy X-ray absorptiometry of the lumbar spine to measure TBS
      and bone mineral density (BMD). Bone marrow edema (BME) on MRI was considered an
      inflammatory lesion. The presence, depth (>1 cm), and intensity of BME on MRI
      were scored for the 1st-4th lumbar spine segments. Inflammatory markers and
      spinal structural damage scores at the time of MRI examination were recorded. The
      association between inflammatory activity score on MRI and TBS was evaluated.
      RESULTS: Among the 97 patients, 52 had BME on spinal MRI (L1-L4). The mean TBS
      values were 1.38 +/- 0.11 and 1.43 +/- 0.11 for patients with and without BME,
      respectively (p = .022). Total inflammatory activity scores on spinal MRI
      correlated negatively with TBS, but not with BMD. Patients with a TBS value
      representing a high fracture risk had more deep BME (>1 cm) (p = .048) on MRI.
      After adjustment for age, symptom duration, and lumbar spinal structural damage,
      the TBS decreased as inflammation severity on MRI increased (p = .026).
      DISCUSSION: In AS patients, inflammation on spinal MRI was negatively correlated
      with TBS. The severity of local bone inflammation in the spine was associated
      with poor bone quality. These findings suggest that the control of active bone
      inflammation may be effective for preventing osteoporosis in AS patients.

PMID- 30092688
TI  - Reply to Tobin and Keegan's "Reply to Idiopathic Central Nervous System
      Inflammatory Disease in the Setting of HLA-B27 Uveitis".

PMID- 30092689
TI  - Reminiscence therapy for dementia: an abridged Cochrane systematic review of the
      evidence from randomized controlled trials.
AB  - INTRODUCTION: Reminiscence therapy (RT) is a popular psychosocial intervention
      widely used in dementia care. It involves discussion of past events and
      experiences, using tangible prompts to evoke memories or stimulate conversation.
      Areas covered: The aim of this review is to evaluate the effectiveness of RT for
      people with dementia. It includes studies from the specialized register of the
      Cochrane Dementia and Cognitive Improvement Group (ALOIS). Searches yielded 185
      records of which 22 (n = 1972) were eligible for inclusion. The meta-analysis
      comprised of data from 16 studies (n = 1749 participants). The review included
      four large multicenter high-quality studies and several smaller studies of
      reasonable quality. Outcomes of interest were quality of life, communication,
      depression, and cognition at posttreatment and later follow-up. Expert
      commentary: RT has the potential to improve psychosocial outcomes for people with
      dementia. Effects are small and can be inconsistent, varying across intervention
      modality and setting. Individual approaches were associated with improved
      cognition and mood. Group approaches were linked to improved communication. The
      impact on quality of life appeared most promising in care home settings.
      Diversity in reminiscence approaches makes it difficult to compare them, and the
      field would benefit from the development, evaluation, use, and sharing of
      standardized approaches.

PMID- 30092690
TI  - Intranasal inactivated influenza vaccines for the prevention of seasonal
      influenza epidemics.
AB  - INTRODUCTION: Intranasal influenza vaccines are expected to confer protection
      among vaccine recipients by successful induction of mucosal immune response in
      the upper respiratory tract. Though only live attenuated influenza virus vaccines
      (LAIVs) are licensed and available for intranasal use in humans today, intranasal
      inactivated influenza vaccines (IIVs) are currently under reconsideration as a
      promising intranasal influenza vaccine. Areas covered: This review addresses the
      history of intranasal IIV research and development, along with a summary of the
      studies done so far to address the mechanism of action of intranasal IIVs. Expert
      commentary: From numerous in vitro and in vivo studies, it has been shown that
      intranasal IIVs can protect hosts from a broad spectrum of influenza virus
      strains. In-depth studies of the mucosal antibody response following intranasal
      IIV administration have also elucidated the detailed functions of secretory IgA
      (immunoglobulin A) antibodies which are responsible for the mechanism of action
      of intranasal vaccines. Safe and effective intranasal IIVs are expected to be an
      important tool to combat seasonal influenza.

PMID- 30092691
TI  - Ebola virus - prospects for a novel virus-like-particle-expressing modified
      vaccinia Ankara-based vaccine.

PMID- 30092692
TI  - Fungal Osteomyelitis in Diabetic Foot Infections: A Case Series and Comparative
      Analysis.
AB  - Fungal osteomyelitis (OM) is relatively rare. There is scarce literature
      discussing fungal OM in diabetic foot infections (DFIs). This case series
      explores the clinical characteristics of patients treated at a large tertiary
      academic center for DFI and found to have a causative agent of fungal origin in
      their bone on surgical intervention. Between July 2017 and March 2018, a
      prospective longitudinal analysis was performed of patients with diabetes
      admitted to our institution who underwent operative management of OM.
      Demographic, clinical, radiographic, and laboratory data were collected for all
      patients. Data between bacterial and fungal OM cohorts was analyzed for
      differences and similarities in patient characteristics and outcomes. All
      patients were followed 20 weeks postoperatively. Five patients with fungal OM
      were identified from the 35 cases where OM was confirmed through podiatric
      surgical intervention. In each fungal case, a Candida species was isolated from
      operative bone culture which included subspecies Candida albicans, C
      parapsilosis, and C glabrata. A P value ?.05 was found in clinical
      characteristics between our cohorts. Wound healing was achieved in 40% of
      patients with fungal OM, and oral fluconazole successfully treated Candida OM in
      the cases that achieved healing. Diabetes can increase the risk of Candida OM. In
      DFIs, fungus can impede wound healing if not recognized and treated. Because
      Candida OM is typically indolent in nature, bone biopsy and mycological culture
      is recommended for definitive diagnosis and treatment.

PMID- 30092693
TI  - Comorbidities, age, and other patient-related predictors of allogeneic
      hematopoietic cell transplantation outcomes.
AB  - INTRODUCTION: Allogeneic hematopoietic cell transplantation (HCT) provides
      potential cure to a large number of malignant and nonmalignant hematological
      disorders. With the development of non-myeloablative and reduced-intensity
      conditioning regimens, allogeneic HCT can nowadays be offered to a number of
      older or medically unfit patients. Up until the twenty-first century,
      chronological age was considered a hypothetical barrier. Recent reports, however,
      have shown that comorbidities, function, and other patient-related factors
      influence HCT outcomes at a higher magnitude than age alone. Areas covered: To
      define the eligibility of older or medically unfit patients for allogeneic HCT, a
      range of factors have to be considered. To solve this considerable issue, we need
      to further understand the mechanism and consequences of aging, such as chronic
      inflammation, sarcopenia, and especially the structure of frailty. Domains
      covering functional, physical, mental, social, nutritional, bone, and other
      health statuses should be evaluated and considered. Expert commentary: In this
      review we merge the current assessment tools with the potential approaches to
      objectify functional resources, as well as with possible methods to improve these
      resources in older or otherwise medically unfit patients prior to allogeneic HCT.

PMID- 30092694
TI  - Most children who are allergic to cow's milk tolerate yogurt.
AB  - Objective Cow's milk allergy is the most common food allergy in childhood.
      Changes occur in the protein structure of milk during yogurt fermentation. This
      study aimed to determine whether children who are diagnosed with a cow's milk
      allergy can tolerate yogurt. Methods We performed a yogurt challenge test on 34
      children who were diagnosed with a cow's milk allergy in our Pediatric Allergy
      Outpatient Clinic. The mean age of 24 male and 10 female children was 24 +/- 13
      months. Results A reaction was observed in 17 (50%) patients, whereas no reaction
      was observed in the other 17 (50%) during an oral yogurt challenge test that was
      performed in all of the 34 patients with a cow's milk allergy. Cow's milk
      specific immunoglobulin E levels were significantly lower in the group of
      children who could tolerate yogurt than in the group of children who could not
      tolerate yogurt. Conclusion Yogurt is tolerated by half of children with a cow's
      milk allergy when subjected to a challenge test performed with yogurt, which is
      consumed as much as milk in Turkey.

PMID- 30092695
TI  - l-Leucine influx through Slc7a5 regulates inflammatory responses of human B cells
      via mammalian target of rapamycin complex 1 signaling.
AB  - OBJECTIVES: Increasing evidence has revealed the close correlation between immune
      cell functions and their intracellular metabolism. Mammalian target of rapamycin
      complex 1 (mTORC1) is the important metabolism-modulating signal that regulates
      cellular activities. In certain types of cell, it is known that mTORC1 activation
      depends on influx of l-leucine through an amino acid transporter, Slc7a5. In B
      cells, however, the expression and the role of Slc7a5 have never been
      investigated. METHODS: CD19+ B cells were obtained from peripheral blood of
      healthy adults and stimulated by a toll-like receptor 9 ligand, CpG
      oligodeoxynucleotides. The expression of Slc7a5 and l-leucine uptake were
      evaluated by RT-PCR, flow cytometry and radioisotope assay. Then the effect of
      Slc7a5 inhibition on mTORC1 activity, plasmablast differentiation and production
      of IgG and inflammatory cytokines were analyzed. RESULTS: CpG stimulation
      significantly induced the expression of Slc7a5 in B cells, resulting in l-leucine
      influx. Furthermore, inhibition of Slc7a5 abrogated mTORC1 activation,
      plasmablast differentiation, and production of IgG and inflammatory cytokines in
      CpG-stimulated B cells. CONCLUSION: l-leucine influx through Slc7a5 critically
      regulates mTORC1 activity and the immunological responses of human B cells.
      Slc7a5-mTORC1 pathway may provide a novel therapeutic strategy for autoimmune
      diseases.

PMID- 30092696
TI  - Effects of traumatic brain injury on sleep and enlarged perivascular spaces.
AB  - Clearance of perivascular wastes in the brain may be critical to the pathogenesis
      of amyloidopathies. Enlarged perivascular spaces (ePVS) on MRI have also been
      associated with amyloidopathies, suggesting that there may be a mechanistic link
      between ePVS and impaired clearance. Sleep and traumatic brain injury (TBI) both
      modulate clearance of amyloid-beta through glymphatic function. Therefore, we
      sought to evaluate the relationship between sleep, TBI, and ePVS on brain MRI. A
      retrospective study was performed in individuals with overnight polysomnography
      and 3T brain MRI consented from a single site ( n = 38). Thirteen of these
      individuals had a medically confirmed history of TBI. ePVS were visually assessed
      by blinded experimenters and analyzed in conjunction with sleep metrics and TBI
      status. Overall, individuals with shorter total sleep time had significantly
      higher ePVS burden. Furthermore, individuals with TBI showed a stronger
      relationship between sleep and ePVS compared to the non-TBI group. These results
      support the hypothesis that ePVS may be modulated by sleep and TBI, and may have
      implications for the role of the glymphatic system in ePVS.

PMID- 30092697
TI  - The Swedish Heart Failure Registry: a living, ongoing quality assurance and
      research in heart failure.
AB  - Heart failure (HF) represents a global pandemic. Although in HF with reduced
      ejection fraction (HFrEF) randomized controlled trials have provided effective
      treatments, prognosis still remains poor, with signals of undertreatment. HF with
      mid-range EF (HFmrEF) has no evidence-based therapy, and its characterization is
      ongoing. Trials in HF with preserved EF (HFpEF) have failed to provide any
      effective treatment, but there are several concerns about their design. Thus,
      current challenges in the HF field are: 1) optimizing the use of existing
      treatments in HFrEF; 2) developing and proving efficacy of new treatments, and of
      new use of existing treatments in HFpEF and HFmrEF. Here we describe how registry
      based research can improve knowledge addressing the unmet needs in HF, and in
      particular we focus on the contribution of the Swedish Heart Failure Registry to
      this field.

PMID- 30092698
TI  - The right way for nurses to prescribe, administer and critique digital therapies.
AB  - Nurses should be mindful that prescribing and administering digital therapies
      comes with patient safety responsibilities. Due diligence is required by nurses
      to ensure that they are prescribing and administering digital therapies to ensure
      they are safe practitioners in this new health field. Nurses without requisite
      digital literacy and critiquing skills should consider what actions they need to
      undertake to up-skill, if it is required, to maintain their safe practice
      standards [Wilson, 2017. E Mental Health. Mental Health: A perosn-centred
      Approach. N. Procter, H. Hamer, D. McGarry, Wilson R. L. and T. Frogatt. Port
      Melbourne: Cambridge University Press].

PMID- 30092699
TI  - "As Natural as the Air Around Us": On the Origin and Development of the Concept
      of Structural Violence in Health Research.
AB  - This article examines the concept of "structural violence." Originating in the
      work of Johan Galtung in 1969 and popularized by Paul Farmer, structural violence
      is increasingly invoked in health literature. It is a complex concept - rich in
      its explanatory potential but vague in its operational definition and arguably
      limited in its theoretical precision. Its potential lies in the focus it gives to
      the deep structural roots of health inequities; in contrast to the more passive
      term "social determinants of health," structural violence explicitly identifies
      social, economic, and political systems as the causes of the causes of poor
      health. It is also evocative in its framing of health inequities as an act of
      violence. Yet the formulation of structure used in this literature is largely
      atheoretical and, by extension, apolitical. Development of the concept hinges on
      clarifying the precise aspects of structure it points to (perhaps through using
      the concept in conjunction with larger theoretical frameworks) as well as
      improving operational definitions to enable its use in quantitative social
      epidemiology. We argue that the concept of structural violence can provide a
      useful lens for understanding health inequities, but its full potential is only
      realized when combined with larger theoretical frameworks.

PMID- 30092700
TI  - Ethnographic reflections on communicative inequities, global health
      relationships, and two decades of HIV in the Bolivian press.
AB  - This article draws on two decades of media representations of HIV, ethnographic
      research among people living with HIV, and an analysis of global health programms
      in Bolivia. In doing so, we chart the evolution of media representations in
      relation to the global health context and the implications of these
      representations for people living with HIV. Our overarching argument is that
      media discourses on HIV in Bolivia have consistently been produced in a context
      of an unequal balance of power between global health bodies and local actors.
      This power imbalance has enabled global health bodies operating in Bolivia to
      maintain authority in producing local narratives about HIV, even when these
      narratives do not adequately capture the particularities of the Bolivian context.
      The mismatch between dominant global health narratives that have infiltrated the
      Bolivian media and ethnographic realities can have deleterious effects on people
      living with HIV. We draw on the concept communicative inequities to highlight how
      global health bodies shape dominant media narratives and the ways these dominant
      narratives at times misrepresent ethnographic realities. Thus, a media analysis
      informed by ethnographic experiences offers a unique lens for interrogating the
      implications of global health interventions.

PMID- 30092701
TI  - Exploring neuropsychological predictors of ADHD remission or persistence during
      adulthood.

PMID- 30092702
TI  - Work Preferences and General Abilities Among US Pharmacy Technicians and Danish
      Pharmaconomists.
AB  - INTRODUCTION: The importance of pharmacy support personnel is increasingly
      recognized. Studies have evaluated workplace issues and evolving roles; however,
      needed information from technicians themselves is scarce. The purpose of this
      study was to examine preferences for work activities and the general abilities of
      US pharmacy technicians and Danish pharmaconomists. METHODS: Surveys were
      administered to random samples of US technicians in 8 states and the general
      population of Danish pharmaconomists. Respondents indicated their preference for
      involvement in a set of work activities in community or hospital pharmacy on
      numeric scales. They also self-assessed their level of ability on facets
      associated with professional practice, in general. Descriptive results were
      tabulated, and bivariate tests were conducted on total general abilities ratings.
      RESULTS: The 494 technicians and 313 pharmaconomists provided similar ratings on
      many activities. In community pharmacy, US technician ratings for performance of
      activities were generally higher than those of pharmaconomists; however,
      pharmaconomists rated certain "higher order" communication activities quite
      highly, such as discussing lifestyle changes with the patient. In hospital
      practice, Danish pharmaconomists provided low preferences for medication handling
      but high preferences for communication activities. General ability ratings were
      given high self-evaluations, but lower on some components, such as keeping up
      with the profession. Employer commitment was a strong correlate for both.
      CONCLUSIONS: Evaluation of preferred work activities and general abilities were
      likely reflected in different scopes of practice between the two and could be
      insightful for education and work redesign in both countries, particularly the
      United States, as leaders evaluate shifts in technician professionalization.

PMID- 30092703
TI  - Expected Lifetime in Different Employment Statuses: Evidence From the Economic
      Boom-and-Bust Cycle in Spain.
AB  - This article analyses the impact of the recent economic crisis on the expected
      time spent in different employment statuses in Spain. Using data from the
      Economically Active Population Survey and life tables, we estimate the expected
      time in work, unemployment, retirement, and other types of economic inactivity
      during the economic boom-and-bust cycle. Differences in expected years of life
      spent in different employment statuses are decomposed into effects of mortality
      and employment behavior. Our results show that men's working life expectancy is
      much more exposed to economic fluctuations. The impact of the ebbs and flows of
      the business cycle among women is mitigated by the long-term female trend of
      growing participation in the labor market associated with the increasing
      educational attainment of women. In addition, the improvement in mortality only
      partially contributes to gains in time spent in each status, while the main
      effects correspond to changes in labor market participation.

PMID- 30092704
TI  - Nutrient composition and dietary diversity of on-site lunch meals, and
      anthropometry of beneficiary children in private and public primary schools in
      Ghana.
AB  - BACKGROUND: On-site lunch provided through the Ghana School Feeding Programme is
      expected to be nutritionally adequate thereby contributing to reducing hunger and
      malnutrition. AIM: The aim of this study was to assess the dietary diversity and
      nutrient composition of on-site school lunch and estimate the extent to which it
      met the Food and Agriculture Organization Reference Nutrient Intakes for children
      aged 3-12 years. METHODS: In this cross-sectional food consumption survey, on
      site lunch menus were reviewed, dietary diversity assessed and meal
      preparation/serving observed during a typical school week. Three randomly
      selected portion sizes were weighed and the average weight (grams) entered into
      the RIING nutrient software to estimate the nutrient composition. Anthropometry
      of participants enrolled in seven public ( n = 113) and six private ( n = 216)
      primary schools in Hohoe municipality, Ghana was analysed using World Health
      Organization Anthroplus software. RESULTS: The menu consisted largely of energy
      dense staples, some vegetables and fish. Eggs, dairy and fruits were never
      served. Meals served in the public and private schools were statistically
      similar. Fat (23.8 vs. 27.7 g), iron (3.0 vs. 2.8 mg), vitamins A (417.3 vs.
      280.8 ug retinol equivalent) and C (25.1 vs. 16.5 mg) requirements were fully
      met. Energy (420.6 vs. 462.2 kcal), protein (6.8 vs. 6.8 g), thiamin (0.18 vs.
      0.17 mg) and zinc (1.3 vs. 1.2 mg) were 50-75% met. Calcium (62.6 vs. 61.4 mg),
      riboflavin (0.09 vs. 0.07 mg) and niacin (1.6 vs. 1.3 mg) were 26-37% met.
      Concerning nutritional status, prevalence of stunting (8.9% vs. 7.9%),
      underweight (3.6% vs. 5.7%), thinness (1.8% vs. 3.7%) and overweight/obesity
      (3.5% vs. 4.2%) were also statistically similar. CONCLUSION: Enhancing dietary
      diversity is crucial to achieving nutrient-dense school meals.

PMID- 30092705
TI  - Experimental ischemic stroke induces long-term T cell activation in the brain.
AB  - Mounting evidence has demonstrated that both innate and adaptive immune cells
      infiltrate into the brain after ischemic stroke. T cell invasion has been found
      in the ischemic region up to one month post experimental ischemic stroke and has
      been shown to persist for years in stroke patients. However, the function and
      phenotypic characteristics of the brain invading T cells after ischemic stroke
      have not been investigated. In the current study, we determined the function of
      brain invading T cells in the acute and chronic phase following experimental
      ischemic stroke induced by transient middle cerebral artery occlusion. We
      observed a significant increase of CD4+ and CD8+ T cells presented in the peri
      infarct area at up to one month after experimental ischemic stroke. The brain
      invading T cells after ischemic stroke demonstrated close interaction with active
      astrocytes and a progressive proinflammatory phenotype as evidenced by the
      increased expression of T cell activation markers CD44 and CD25, proinflammatory
      cytokines INF-gamma, IL-17, IL-10, TNF-alpha, and perforin, with corresponding
      transcriptional factors T-bet and RORc. Our results indicated a prolonged
      activation of brain invading CD4+ and CD8+ T cells after ischemic stroke which
      may play a role in the neural repair process after stroke.

PMID- 30092706
TI  - Learning to liaise: using medication administration role-play to develop teamwork
      in undergraduate nurses.
AB  - AIM: To describe undergraduate nursing students' situational awareness and
      understanding of effective liaison and collaboration within the nursing team
      during interrupted medication administration. BACKGROUND: Medication errors
      related to interruptions are a major problem in health care, impacting on patient
      morbidity and mortality and increasing the burden of related costs. Effective
      liaison, teamwork and situation awareness are requisite skills for nurses to
      facilitate the safe management of interruptions during medication administration.
      METHOD: A role-play simulation was offered to 528 second-year undergraduate
      Bachelor of Nursing students. Qualitative written reflective responses were
      subsequently collected and subject to thematic analysis to derive themes.
      RESULTS: Participants (451:528) reported an improved understanding of an
      unfamiliar and challenging situation that required cooperation and collaboration
      amongst the nursing team to improve outcomes. CONCLUSION(S): This simulation
      exposed undergraduate nurses with limited clinical experience to a situation
      otherwise unavailable to them. The skills required to engage in effective liaison
      and teamwork in dynamic situations are vital elements in achieving quality care
      and must begin to be taught at an undergraduate level.

PMID- 30092707
TI  - Memory for dangers past: threat contexts produce more consistent learning than do
      non-threatening contexts.
AB  - In earlier work we showed that individuals learn the spatial regularities within
      contexts and use this knowledge to guide detection of threatening targets
      embedded in these contexts. While it is highly adaptive for humans to use
      contextual learning to detect threats, it is equally adaptive for individuals to
      flexibly readjust behaviour when contexts once associated with threatening
      stimuli begin to be associated with benign stimuli, and vice versa. Here, we
      presented face targets varying in salience (threatening or non-threatening) in
      new or old spatial configurations (contexts) and changed the target salience
      (threatening to non-threatening and vice versa) halfway through the experiment to
      examine if contextual learning changes with the change in target salience.
      Detection of threatening targets was faster in old than new configurations and
      this learning persisted even after the target changed to non-threatening.
      However, the same pattern was not seen when the targets changed from non
      threatening to threatening. Overall, our findings show that threat detection is
      driven not only by stimulus properties as theorised traditionally but also by the
      learning of contexts in which threatening stimuli appear, highlighting the
      importance of top-down factors in threat detection. Further, learning of contexts
      associated with threatening targets is robust and speeds detection of non
      threatening targets subsequently presented in the same context.

PMID- 30092708
TI  - Reappraising faces: effects on accountability appraisals, self-reported valence,
      and pupil diameter.
AB  - Many of our emotions arise in social contexts, as we interact with and learn
      about others. What is not yet clear, however, is how such emotions unfold when we
      either react to others or attempt to regulate our emotions. To address this
      issue, 30 healthy volunteers reacted to or reappraised positive or negative
      information that was paired with neutral faces. While they were doing this task,
      we assessed pupillary responses. We also asked participants to provide ratings of
      accountability and experienced emotion. Findings indicated that appraised
      accountability increased in response to emotional information, and changes in
      accountability were associated with commensurate changes in valence reports and
      increased pupil diameter. During reappraisal, accountability and emotion
      decreased, but pupil diameter increased. The findings highlight the importance of
      accountability appraisals during the generation and regulation of emotional
      reactions to others, while also documenting pupillary increases during emotional
      reactivity and regulation.

PMID- 30092709
TI  - Limited benefit of slow rewarming after cerebral hypothermia for global cerebral
      ischemia in near-term fetal sheep.
AB  - The optimal rate of rewarming after therapeutic hypothermia for neonatal hypoxic
      ischemic encephalopathy is unknown, although it is widely suggested that slow
      rewarming is beneficial. Some preclinical studies suggest better outcomes with
      slower rewarming, but did not control for the duration of hypothermia. In this
      study, near-term fetal sheep (0.85 gestation) received 30 min cerebral ischemia
      followed by normothermia, 48 h hypothermia with rapid rewarming over 1 h, 48-h
      hypothermia with slow rewarming over 24 h, or 72-h hypothermia with rapid
      rewarming. Slow rewarming after 48 h of hypothermia improved recovery of EEG
      power compared with rapid rewarming ( p < 0.05), but was not different from rapid
      rewarming after 72 h of hypothermia. At seven days recovery, neuronal survival
      was partially improved by both fast and slow rewarming after 48-h hypothermia,
      but less than 72-h hypothermia in the cortex and CA4 ( p < 0.05). In conclusion,
      although electrographic recovery was partially improved by slow rewarming over 24
      h following cerebral hypothermia for 48 h, optimal neuroprotection was seen with
      hypothermia for 72 h with rapid rewarming, suggesting that the overall duration
      of cooling was the critical determinant of outcomes after therapeutic
      hypothermia.

PMID- 30092710
TI  - Foreign body granuloma reaction following SIRT mimicking peritoneal metastases: a
      word of caution.
AB  - Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver
      malignancy with poor survival rates. Surgical resection is the only curative
      treatment option, yet only a small portion of cases are resectable. In
      unresectable situations, suggested therapy consists of a systemic chemotherapy
      regimen with cisplatinum and gemcitabine. Selective internal radiation therapy
      (SIRT) has been proposed as an alternative treatment option and may lead to
      downstaging of unresectable iCCA to surgery. We present a case of a female
      patient diagnosed with an unresectable iCCA treated with SIRT in order to obtain
      downstaging. Explorative laparoscopy three months later showed multiple
      peritoneal lesions in the left upper quadrant, mimicking peritoneal metastases.
      Anatomopathological investigation showed a foreign body granuloma surrounding the
      SIRT resin particles. These findings have important consequences, as the presence
      of peritoneal metastases implies a palliative situation. Anatomopathological
      confirmation of any intra-abdominal lesion mimicking peritoneal metastases should
      be carried out.

PMID- 30092711
TI  - Effects of cognitive-behavioural therapy on anxiety, depression and condom use in
      people with HIV in Mexico City: a pilot study.
AB  - Anxiety and depression in people living with HIV (PLWH) are negatively associated
      with healthy sexual behaviours. We pilot-tested a Cognitive-Behavioural Therapy
      (CBT)-based intervention to reduce anxiety and depression, aimed to increase
      serostatus disclosure to sexual partners, quality of sexual life (QoSL) and
      condom use. The study had a single-case experimental design (AB) with follow-up
      measures. Eleven PLWH with moderate/severe anxiety/depression received six-module
      CBT intervention delivered in ten one-hour individual weekly sessions. Anxiety,
      depression, consistent/correct condom use and QoSL were measured. Depression and
      anxiety decreased after the intervention (depression baseline [BL] Mdn = 21,
      final [F] Mdn = 3, z = -2.934, p = .003; anxiety BL Mdn = 30, F Mdn = 4, z = 
      2.941, p = .003). QoSL improved (BL Mdn = 28, F Mdn = 13, z = -2.625, p = .009),
      along with participants' ability to use condoms (57.14 vs.100, z = -2.937, p =
      .003). Effect size was large, changes were maintained at follow-up measurements.
      The CBT intervention had positive effects in reducing anxiety and depression,
      which could facilitate the acquisition of healthy sexual behaviours. Further
      studies are important to clarify the benefits of targeting emotional variables to
      improve wellbeing and prevention behaviours in PLWH.

PMID- 30092712
TI  - Induction of Pyruvate Dehydrogenase Kinase 1 by Hypoxia Alters Cellular
      Metabolism and Inhibits Apoptosis in Endometriotic Stromal Cells.
AB  - Endometriosis is a common gynecological disease, which is defined as the growth
      of endometrial tissues outside the uterine cavity. It often causes dysmenorrhea,
      dyspareunia, chronic pelvic pain, and infertility in reproductive-age women.
      However, the pathogenesis of endometriosis remains largely unclear. Since our
      previous study revealed that ectopic endometriotic stromal cells experience
      greater hypoxic stress than their eutopic counterparts, we aim to investigate
      whether the metabolic properties are changed in the ectopic endometriotic stromal
      cell when compared to its eutopic counterpart. Here, we found the expression of
      pyruvate dehydrogenase kinase 1 (PDK1), a critical enzyme in regulating glucose
      metabolism, was increased in ectopic stromal cells. Molecular characterization
      reveals that overexpression of PDK1 is induced by hypoxia through transcriptional
      regulation. Upregulation of PDK1 in ectopic endometriotic stromal cells was
      accompanied by increases in lactate production and oxygen consumption rate when
      compared to eutopic endometrial stromal cells. Furthermore, our data showed that
      inhibition of PDK1 activity by treatment with dichloroacetate inhibits the
      lactate production and oxygen consumption rate of ectopic stromal cells. In
      addition, hypoxia-induced PDK1 expression prevented cells from H2O2- and low
      nutrient-induced cell death. These data indicate that ectopic endometriotic cells
      may adapt to hypoxic microenvironment via upregulating PDK1 and reprogramming
      metabolism, which provides a survival advantage in the hostile peritoneal
      microenvironment.

PMID- 30092713
TI  - Missing the early signs of thiamine deficiency. A case associated with a liquid
      only diet.
AB  - BACKGROUND: Wernicke encephalopathy (WE) predominantly occurs in alcoholic
      patients. Few case reports have described this diagnosis as a result of dieting.
      The diagnosis is often missed or delayed resulting in permanent and severe
      neurologic sequelae and even death. The typical neurological signs may be absent
      or missed during the early stages of thiamine deficiency. Case report; A 23-year
      old female presented to the hospital with confusion, bilateral lateral rectus
      palsy, and ataxia. Based on the typical neurological triad, WE was suspected. The
      brain MRI was also typical for WE. Prompt clinical improvement was seen within
      days after intravenous thiamine supplementation. A detailed medical history
      revealed that during the past 3 months she had been following a liquid-only diet
      and had lost about 30 kg. During that time, she had visited the emergency
      department on multiple occasions due to fatigue, nausea, and vomiting.
      CONCLUSION: A high level of suspicion is required by physicians to recognize that
      fatigue, nausea, and vomiting may represent early signs of thiamine deficiency in
      patients at risk for nutritional deficiencies. Empirical thiamine supplementation
      may be reasonable in such cases.

PMID- 30092714
TI  - "I'm not going to walk, just for the sake of walking...": a qualitative,
      phenomenological study on physical activity during hospital stay.
AB  - PURPOSE: To understand beliefs, thoughts, attitudes, and experiences related to
      physical activity during hospital stay in patients and health care providers.
      METHODS: A qualitative, interpretive, phenomenological study examined the common
      meaning and lived experiences of patients and health care providers related to
      inpatient physical activity. Data from semi-structured interviews were analysed
      using qualitative content analysis. RESULTS: A total of 42 participants (18
      patients and 24 health care providers) were interviewed. Patients and health care
      providers described physical activity as a purposeful activity to achieve a goal.
      In contrast, they talked about physical and mental rest to balance inpatient
      physical activity. Furthermore, the hospital environment was felt to discourage
      patients to be physically active with care centred around the hospital beds,
      frequent disturbances of rest on hospital rooms, and dependency of patients on
      health care providers as important sources. The ability of patients to perform
      physical activity was associated with feelings, such as freedom and autonomy.
      CONCLUSIONS: Physical activity during hospital stay is a purposeful activity to
      achieve a goal, and should be well-balanced with both physical and mental rest
      according to patients and health care providers. In addition, the hospital
      environment seems to be a source of low inpatient physical activity. Implications
      for rehabilitation Health care providers should offer meaningful activities to
      engage patients' interest in being physically active during hospital stay.
      Tailored interventions aiming to increase inpatient physical activity should be
      balanced with phases of both physical and mental rest. A change of the hospital
      environment in both culture and the build environment is needed to elicit
      physical activity in patients during hospital stay.

PMID- 30092715
TI  - Sequestration of Sulphide from Biogas by thermal-treated iron nanoparticles
      synthesized using tea polyphenols.
AB  - Dark tea-iron nanoparticles (DT-Fe NPs) were prepared using extracts of dark tea
      leaves as a reducing agent, and further underwent thermal treatment in air. The
      H2S removal performances of thermal-treated DT-Fe NPs for biogas were further
      evaluated using a custom-designed fixed-bed reactor (reaction temperature of 250
      degrees C, H2S content of 1%). Significant morphology and chemical composition
      differences were observed when DT-Fe NPs were treated at different temperatures
      (300-800oC). X-ray diffractometer analysis revealed that a phase transition from
      gamma-Fe2O3 to alpha-Fe2O3 occurred under heat treatment. When the thermal
      treatment temperature was 300 degrees C, only alpha-Fe2O3 was detected. Both
      alpha-Fe2O3 and gamma-Fe2O3 were present in the sample treated at 400 degrees C.
      When the thermal treatment temperature was 500-800 degrees C, gamma-Fe2O3 in the
      sample was completely converted to alpha-Fe2O3. The H2S removal capacity is 14.72
      mg H2S/g for DT-Fe NPs without treatment. However, the value increased
      significantly to 408.30 mg H2S/g after 400 degrees C thermal treatment, which can
      be explained by the formation of highly active gamma-Fe2O3. The reaction product
      of thermal-treated DT-Fe NPs at 400 degrees C and H2S were further characterized
      by X-ray diffractometer and X-ray photoelectron spectroscopy. The results showed
      that it is composed of FeS2 and FeS, in which 72.6% of the sulphur existed as
      disulphide and 27.4% as monosulphide.

PMID- 30092716
TI  - Predicting intramammary infection status at drying off using indirect testing of
      milk samples.
AB  - AIMS To evaluate the Rapid Mastitis test (RMT, or California Mastitis test) and
      electrical conductivity (EC) at drying off when used alone or in combination with
      herd test data (maximum or last herd test somatic cell counts (SCC) before drying
      off), to define cows or quarters with intramammary infection, using
      microbiological culture as the gold standard. METHODS Quarter-level milk samples
      (n=609) from clinically healthy cows (n=153), in three herds in the Waikato
      region of New Zealand, were tested at drying off using the RMT and EC, and were
      collected for microbiological culture. The maximum SCC and the SCC at the last
      herd test of the preceding lactation were determined for each cow. The
      sensitivity, specificity, and positive and negative predictive values for each
      test were calculated for different cut-points, using microbiological culture as
      the gold standard. Receiver operating characteristic curves were generated and
      the area under the curve (AUC) was calculated for each test. The same parameters
      were calculated for combinations of two tests in parallel or in series. RESULTS
      Infection with any pathogen was detected in 62/153 (40.5%) cows and 99/609
      (16.3%) quarters, and with major pathogens in 7/153 (4.6%) cows and 8/609 (1.3%)
      quarters. When predicting infection with any pathogen at the cow-level, the
      coefficient of agreement was highest for SCC (<0.32) and RMT (<0.28) and lowest
      for EC (<0.12); the AUC for RMT and EC when used singly ranged from 0.57-0.69,
      and in combination with SCC ranged from 0.68-0.75. AUC were similar for tests
      that used either the last or the maximum SCC. CONCLUSIONS AND CLINICAL RELEVANCE
      When evaluated singly, RMT and EC had only low to moderate diagnostic utility
      compared to bacteriological culture. When they were combined with SCC and
      interpreted in parallel, the results were improved, but only moderately. For
      herds that conduct herd testing, a single herd test late in lactation was as
      predictive of intramammary infection at drying off as multiple herd tests through
      the lactation. For herds that do not conduct herd testing, RMT has greater
      utility than EC.

PMID- 30092717
TI  - Influence of luminosity, carbon source and concentration of salts in the
      physiology of Chlorella sorokiniana.
AB  - Growth studies are important to increase the knowledge about the physiology of
      microalgae. The development of suitable culture media allows optimum growth to
      each species. The genus Chlorella has the ability to adapt to various
      environmental and nutritional conditions. Thus, the aim of this work was to
      evaluate the physiology of Chlorella sorokiniana CTT 7727 at different growth
      conditions with Basal Bold (BB) medium. For that, heterotrophic, autotrophic and
      mixotrophic cultures were carried out. The maximum specific growth rates (umax),
      the maximum biomass concentrations (Xmax) and cell productivities (PX) were
      calculated for each experiment. Among all the treatments evaluated, that with 24
      h light, 3x BB (g L-1) and CO2 presented a higher umax (0.40 day-1) and maximum
      cell concentration due the increased concentration of nutrients. Replacement of
      dark to light has increased Xmax from 2.3 * 105 to 9.3 * 106 cells mL-1 in
      regular BB medium and 3.6 * 105 to 2.1 * 107 cells mL-1 in 3x BB medium in
      autotrophic cultivations. The PX increased from 2.4 * 104 cells mL-1 h-1 (1x BB
      (g L-1)) to 3.6 * 104 cells mL-1 h-1 (3x BB (g L-1)), in the presence of 24 light
      and CO2. However, the same behaviour was not observed when BB concentration was
      increased 6, 8 or 10 times the initial concentration of BB medium. Experiments
      with pulses of concentrated nutrients showed that declining cells can resume
      their growth after nutrient depletion, but the viability is decreased after
      successive pulses.

PMID- 30092718
TI  - SNP rs10800708 within the KIF14 miRNA binding site is linked with breast cancer.

PMID- 30092721
TI  - Late-Onset Nonthrombotic Left Common Iliac Vein Compression Secondary to
      Degenerative Lumbar Disc: A Case Report of May-Thurner Variant.
AB  - May-Thurner syndrome (MTS) refers to venous outflow obstruction caused by
      extrinsic compression of the left common iliac vein (LCIV) by the overlying
      pulsatile right common iliac artery against lumbar vertebrae. The classic
      clinical presentation is acute unilateral left leg painful swelling due to deep
      venous thrombosis in a young woman in the second or third decade of life. We
      present a case of a 66-year-old woman who presented with late-onset left leg
      swelling caused by nonthrombotic venous hypertension due to degenerative lumbar
      disc bulge leading to LCIV compression against the left common iliac artery which
      was confirmed by computed tomography and intravascular ultrasound. Our case
      highlights the importance of high index of suspicion for MTS in elderly patients
      with unilateral leg swelling and the importance of multimodality imaging for
      understanding the mechanism and appropriate treatment of MTS.

PMID- 30092720
TI  - Cancer Subtype Discovery Using Prognosis-Enhanced Neural Network Classifier in
      Multigenomic Data.
AB  - OBJECTIVE: The main objective in studying large-scale cancer omics is to identify
      molecular mechanisms of cancer and discover novel biomedical targets. This work
      not only discovers the cancer subtypes in genome scale data by using clustering
      and classification but also measures their accuracy. METHODS: Initially,
      candidate cancer subtypes are recognized by max-flow/min-cut graph clustering.
      Finally, prognosis-enhanced neural network classifier is proposed for
      classification. We analyzed the heterogeneity and identified the subtypes of
      glioblastoma multiforme, an aggressive adult brain tumor, from 215 samples with
      microRNA expression (12 042 genes). The samples were classified into 4 different
      classes such as mesenchymal, classical, proneural, and neural subtypes owing to
      mutations and gene expression. The results are measured using the metrics such as
      silhouette width, biological stability index, clustering accuracy, precision,
      recall, and f-measure. RESULTS: Max-flow/min-cut clustering produces higher
      clustering accuracy of 88.93% for 215 samples. The proposed prognosis-enhanced
      neural network classifier algorithm produces higher accuracy results of 89.2% for
      215 samples efficiently. CONCLUSION: From the experimental results, the proposed
      prognosis-enhanced neural network classifier is seen as an alternative, which is
      full of promise for cancer subtype prediction in genome scale data.

PMID- 30092722
TI  - Education, cognitive ability, and cause-specific mortality: A structural
      approach.
AB  - Education is negatively associated with most major causes of death. Prior work
      ignores the premise that cause-specific hazards are interdependent and that both
      education and mortality depend on cognitive ability. We analyse Swedish men aged
      18-63, focusing on months lost due to specific causes-which solves the
      interdependence problem-and use a structural model that accounts for confounding
      due to cognitive ability. In a standard Cox model controlling for Intelligence
      Quotient, improving education is associated with large decreases in mortality for
      major causes of death. In the structural model, improving education is associated
      with a small decrease in months lost for most causes and education levels. Among
      the least educated, however, improving education strongly reduces the months
      lost, mainly those lost from external causes, such as accidents and suicide.
      Results suggest that conventional analysis of education and mortality may be
      biased, even if accounting for observed cognition.

PMID- 30092723
TI  - Double Chimney Technique Using Interwoven Self-Expanding Nitinol Stents to Treat
      Recurrent Nonmalignant Thoracic Central Vein In-Stent Restenosis.

PMID- 30092724
TI  - Evaluation of emission, performance and combustion characteristics of dual
      fuelled research diesel engine.
AB  - This study is intended to examine the ignition characteristics of a cashew nut
      shell biodiesel (C100) along with ethyne (acetylene) as a dual fuel in a diesel
      engine. Cashew nut shell oil is employed in this study owing to non-toxic nature,
      free from sulphur, biodegradable, and free of aromatics. Ethyne gas was
      introduced at different flow rate of 2, 4, 6 litres per minute (lpm).
      Experimental results revealed that duel fuelling ethyne gas to base fuel (C100)
      at 6 lpm reduce 18.1% CO, 9.7% HC, 6.87% Smoke with 11.1% increase in NOx
      emissions. Higher thermal efficiency was observed for ethyne-biodiesel mixture
      than neat biodiesel in all flow rates. Furthermore, the heat release and peak
      pressure were enhanced by duel fuelling ethyne gas to base fuel (C100).

PMID- 30092719
TI  - Auditory and Cognitive Training for Cognition in Adults With Hearing Loss: A
      Systematic Review and Meta-Analysis.
AB  - This systematic review and meta-analysis examined the efficacy of auditory
      training and cognitive training to improve cognitive function in adults with
      hearing loss. A literature search of academic databases (e.g., MEDLINE, Scopus)
      and gray literature (e.g., OpenGrey) identified relevant articles published up to
      January 25, 2018. Randomized controlled trials (RCTs) or repeated measures
      designs were included. Outcome effects were computed as Hedge's g and pooled
      using random-effects meta-analysis (PROSPERO: CRD42017076680). Nine studies, five
      auditory training, and four cognitive training met the inclusion criteria.
      Following auditory training, the pooled effect was small and statistically
      significant for both working memory ( g = 0.21; 95% CI [0.05, 0.36]) and overall
      cognition ( g = 0.19; 95% CI [0.07, 0.31]). Following cognitive training, the
      pooled effect for working memory was small and statistically significant ( g =
      0.34; 95% CI [0.16, 0.53]), and the pooled effect for overall cognition was large
      and significant ( g = 1.03; 95% CI [0.41, 1.66]). However, this was dependent on
      the classification of training approach. Sensitivity analyses revealed no
      statistical difference between the effectiveness of auditory and cognitive
      training for improving cognition upon removal of a study that used a combined
      auditory-cognitive approach, which showed a very large effect. Overall certainty
      in the estimation of effect was "low" for auditory training and "very low" for
      cognitive training. High-quality RCTs are needed to determine which training
      stimuli will provide optimal conditions to improve cognition in adults with
      hearing loss.

PMID- 30092725
TI  - Successful Endovascular Treatment for Aortic Thrombosis Due to Primary
      Antiphospholipid Syndrome: A Case Report and Literature Review.
AB  - A 60-year-old man with a history of Raynaud's phenomenon presented with bilateral
      intermittent claudication and an ulcer on his right toe. The ankle-brachial index
      of the right and left legs was 0.77 and 0.75, respectively. Laboratory data
      showed prolongation of the activated partial thromboplastin time and a positive
      result on the lupus anticoagulant test. Computed tomography angiography revealed
      isolated infrarenal aortic stenosis with irregular surface and noncalcified
      plaques. Intravascular ultrasonography examination demonstrated a noncalcified,
      irregular, and mobile plaque, suggestive of abdominal aortic thrombosis. In
      addition to anticoagulant and dual antiplatelet therapy, endovascular treatment
      was performed. A total of three 40-mm-long balloon-expandable stents were
      successfully implanted on a 15-mm balloon. The final angiography showed good
      results except for minimal plaque shifting in the terminal aorta. Three months
      later, the ulcer resolved and a final diagnosis of primary antiphospholipid
      syndrome (APS) was made. Clinicians should recognize that APS can affect the
      abdominal aorta, leading to aortic thrombosis. Endovascular treatment may be the
      one good treatment option for this rare condition.

PMID- 30092727
TI  - Scientific and Regulatory Policy Committee Points to Consider: Histopathologic
      Evaluation in Safety Assessment Studies for PEGylated Pharmaceutical Products.
AB  - Colorless, intracytoplasmic vacuoles occur in multiple tissues in animals
      following repeated administration of polyethylene glycol (PEG)-conjugated
      molecules. The extent of vacuolation depends on physical characteristics and
      molecular backbone of the PEG and the dose, product, drug target/pharmacology,
      and duration of exposure. The collective experience gathered from multiple
      nonclinical toxicology studies of PEGylated biopharmaceuticals indicates that in
      general, PEG-related vacuolation is not associated with demonstrable cell and
      tissue damage or dysfunction and is reversible with sufficient duration of drug
      free periods. Existing data are insufficient to predict whether nonclinical
      animal species differ in their sensitivity to develop PEG-associated vacuoles;
      however, recent data suggest that there may be species differences. Recent
      comprehensive reviews have addressed the basic challenges in developing PEGylated
      pharmaceutical products, including general reference to and description of PEG
      associated tissue findings. These manuscripts have identified gaps in our current
      understanding of PEG-associated vacuolation, including the lack of a widely
      accepted standardized histological terminology and criteria to record and grade
      the severity of vacuolation as well as insufficient knowledge regarding the
      nature of the contents of these vacuoles. The goal of this article is to help
      address some of the gaps identified above by providing points to consider,
      including a pictorial review of PEG-associated microscopic findings, when
      evaluating and reporting the extent, severity, and significance (adversity or
      lack of adversity) of PEG-associated cytoplasmic vacuolation in safety assessment
      studies. [Box: see text].

PMID- 30092728
TI  - Treatment of advanced non-small cell lung cancer in the elderly.
AB  - INTRODUCTION: Lung cancer is predominantly a disease that affects the elderly;
      about 30-40% of lung cancers are diagnosed in patients aged 70 or more. The
      increasing number of elderly patients over the next decades is generating a new
      social and health problem; despite that, these patients are underrepresented in
      clinical trials and undertreated in clinical practice. Areas covered: The main
      difficulty in treating elderly patients is to maximize the therapy benefits while
      minimizing the treatment risk. Elderly patients show a vulnerable clinical
      profile due to the higher prevalence of comorbid disease, higher polypharmacy
      interactions and aged organ dysfunction that increase the risk of mortality and
      toxicity with cancer treatments compared to younger patients. Expert commentary:
      The choice to treat or not to treat elderly patients cannot be taken only on the
      basis of the chronological age. Thus, the clinical approach should be to select
      patients who are effectively suitable for treatment having a better individual
      functional reserve and a better life expectancy. Elderly patients are a
      heterogeneous population and those who are fit to receive cancer treatment can be
      treated similarly to younger patients.

PMID- 30092726
TI  - Cancer Stem Cells or Tumor Survival Cells?
AB  - Research endeavors originally generated stem cell definitions for the purpose of
      describing normally sustainable developmental and tissue turnover processes in
      various species, including humans. The notion of investigating cells that possess
      a vague capacity of "stamm (phylum)" can be traced back to the late 19th century,
      mainly concentrating on cells that could produce the germline or the entire blood
      system. Lately, such undertakings have been recapitulated for oncogenesis, tumor
      growth, and cancer cell resistance to oncolytic therapies. However, due to the
      complexity and basic life-origin mechanisms comprising the genetic and epigenetic
      repertoire of the stemness in every developing or growing cell, presently there
      are ongoing debates regarding the biological essentials of the stem cell-like
      tumor initiation cells (ie, cancer stem cells; CSCs). This conceptual analysis
      focuses on the potential pitfalls of extrapolating that CSCs bear major traits of
      stemness. We propose a novel nomenclature of Tumor Survival Cells (TSCs) to
      further define tumor cells behaving like CSCs, based on the ruthless and
      detrimental features of Cancer Cell Survivology that appears fundamentally
      different from stem cell biology. Hence, precise academic separation of TSCs from
      all the stem cell-related labels applied to these unique tumor cells may help to
      improve scientific reasoning and strategies to decode the desperado-like survival
      behaviors of TSCs to eventually overcome cancer.

PMID- 30092729
TI  - The risk management of medical device-related pressure ulcers based on the
      Australian/New Zealand Standard.
AB  - Objective To analyse medical device-related pressure ulcer (MDRPU) management
      modes and their possible risks and provide references to treat MDRPUs. Methods
      The Australian/New Zealand Standard (AS/NZS) 4360:2004 risk management standard
      is the first national risk management standard in the world. Zhongshan Hospital
      adopted the standard to establish risk management modes to improve the MDRPU risk
      management process and to register, assess and analyse the key risks for MDRPUs.
      Eight risk types were identified and registered: organization management risk,
      environment risk, patient safety risk, human resource risk, infection risk,
      occupational safety risk, legal risk and reputational risk. Results Following the
      implementation of the AS/NZS 4360:2004 risk management standard in our
      institution, the organization management risk value decreased from 25 to 5; the
      environment risk value decreased from 25 to 5; the patient safety risk value
      decreased from 20 to 3; the human resource risk value decreased from 16 to 4; the
      infection risk value decreased from 9 to 1; the occupational risk value decreased
      from 9 to 6; the legal risk value decreased from 9 to 4; and the reputational
      risk value decreased from 12 to 2. Conclusion The AS/NZS 4360:2004 risk
      management standard was effective in managing the risk of MDRPUs.

PMID- 30092730
TI  - Successful endovascular recanalization of a partially occluded basilar artery
      fenestration.
AB  - A 76-year-old man with a history of arterial hypertension, obstructive sleep
      apnea, dyslipidemia, family history of cardiovascular events, prestroke and
      overweight presented 90 minutes after acute onset of right-sided sensorimotor
      hemiparesis, hemiataxia and dysarthria (National Institutes of Health Stroke
      Scale (NIHSS) 9/42). Magnetic resonance imaging (MRI) revealed a pontine ischemia
      and MR angiography showed a thrombus in the middle to distal portion of the
      basilar artery. Owing to the location, an occlusion of one lumen of a fenestrated
      basilar artery was suspected. Fearing the risk of peripheral dislocation,
      intravenous thrombolysis was withheld after an interdisciplinary discussion and
      direct endovascular thrombectomy (Solitaire stent retriever) was successfully
      performed by passing the stent retriever specifically through the affected lumen
      and between the thrombus and the vascular wall, which would normally be avoided.
      Angiography after complete reperfusion (Thrombolysis in Cerebral Infarction grade
      3) confirmed a fenestration in the middle to distal portion of the basilar artery
      where the thrombus was initially located (blue and green arrow). Follow-up MRI
      after 24 hours showed only minimal ischemic damage in the left pontine area, and
      the patient was discharged home with ambulatory physiotherapy for residual
      minimal gait disturbance (NIHSS 0).

PMID- 30092731
TI  - Scleritis, keratitis, and orbital cellulitis: isolated ocular manifestation of
      systemic lupus erythematosus.
AB  - Systemic autoimmune diseases are associated with ocular inflammatory conditions
      such as episcleritis, scleritis, keratitis, and uveitis. However, ocular
      manifestations have been reported to correlate with the extent of systemic
      disease. We present a patient with scleritis, keratitis, and orbital cellulitis,
      as the isolated manifestation of systemic lupus erythematosus (SLE). No microbial
      etiology was identified and antibiotics did not produce clinical improvement. The
      patient improved significantly with steroids and disease-modifying antirheumatic
      drugs. Although ocular inflammation has been previously remarked in SLE of
      systemic severity, in this case there were no other organs with SLE involvement.
      We briefly discuss the ocular manifestations of SLE, which can involve all
      segments of the eye, including cornea, sclera, retina, uvea, optic nerve, and
      orbit.

PMID- 30092732
TI  - Damage accrual in systemic lupus erythematosus in Dominicans in New York City and
      the Dominican Republic.
AB  - Objectives Hispanics with systemic lupus erythematosus (SLE) in the United States
      have more severe disease and damage accrual compared with whites. Data on
      Hispanics of similar ancestry in geographically different locations is limited
      but essential in defining genetic and environmental factors for SLE. This study
      evaluates SLE disease burden in two Dominican communities, Washington Heights in
      New York City (NYC) and Santiago in the Dominican Republic (DR). Methods Disease
      activity (SLE Disease Activity Index 2000 (SLEDAI-2K)) and damage (Systemic Lupus
      International Collaborating Clinics/American College of Rheumatology Damage Index
      (SDI)) were cross-sectionally measured in 76 Dominican SLE patients from the
      Columbia University Lupus Cohort in NYC and compared with 75 Dominican SLE
      patients living in Santiago in the DR. Results Mean (+/-SD) age was 40 (+/-14)
      and 36 (+/-11) years for NYC and DR patients, respectively. Median disease
      duration was 8 years. Disease activity was mild in both groups (SLEDAI-2K of 3 in
      NYC versus 4 in the DR). NYC Dominicans had more discoid lesions, positive anti
      dsDNA, and anti-SSB antibodies. Dominicans in the DR used more corticosteroids,
      had less medical insurance, lower educational level, and were more likely to be
      unemployed, whereas more Dominicans in NYC smoked. NYC patients had a higher SDI
      compared with SLE patients in the DR (0.96 versus 0.24, p < 0.0001). Statistical
      significance was maintained in adjusted analysis (1.26 versus 0.57, p < 0.0001).
      Conclusion SLE Dominican patients in NYC had a higher SDI than those in the DR.
      Longitudinal studies are needed to ascertain whether this difference is due to
      biological, environmental factors, immigration patterns or a survival bias.

PMID- 30092733
TI  - An unusual case of inflammatory meningitis in a young man with systemic lupus
      erythematosus.
AB  - We describe a man presenting with unusual neurological manifestations of systemic
      lupus erythematosus (SLE) including pachymeningitis, aseptic meningitis and
      encephalitis with grossly elevated cerebrospinal fluid protein, responding to
      immunosuppression. Initially he had intermittent dysarthria, dysphasia and
      unilateral upper limb weakness. One month later he experienced dysphasia, right
      sided hemiparesis and confusion. Cerebrospinal fluid (CSF) analysis showed a
      white cell count of 70 x 106/litre and an unusually elevated protein level of
      5.39 g/litre. An MRI brain showed dural and leptomeningeal enhancement compatible
      with a meningitic process. He improved with cefotaxime and aciclovir. On day
      seven of antimicrobials he developed left-sided weakness, sensory inattention and
      a left homonymous hemianopia. He responded well to intravenous
      methylprednisolone. On switching to oral prednisolone he developed expressive
      dysphasia, a right inferior quadrantanopia and seizures. His bloods were
      suggestive of macrophage activation syndrome. The patient improved with
      methylprednisolone and intravenous immunoglobulins, and the improvement was
      sustained on switching back to oral prednisolone. The prevalence of
      neuropsychiatric manifestations of SLE varies between 14 and 80% and according to
      the American College of Rheumatology includes 19 conditions. This case is unique
      because although some features were in keeping with aseptic meningitis the MRI
      appearances were also suggestive of pachymeningitis.

PMID- 30092734
TI  - The current role for clinical and renal histological findings as predictor for
      outcome in Australian patients with lupus nephritis.
AB  - Objectives To investigate the current demographic, clinical and histological
      characteristics of patients with lupus nephritis (LN) in Western Australia (WA)
      with regards to their predictive value for patient and renal outcome. Methods
      Retrospective study of adult systemic lupus erythematosus (SLE) patients with a
      first renal biopsy demonstrating LN between 1997 and 2017 at a metropolitan
      tertiary hospital in WA. Clinical data were collected at baseline and last follow
      up with renal biopsy findings classified by International Society of Nephrology
      (ISN) criteria. Annual incidence rates (AIRs)/100,000, Kaplan-Meyer curves and
      Cox regression hazard ratio for independent predictors for patient and renal
      survival were applied. Results The AIR was 3.3, 3.1 and 0.4 for Asian ( n = 29),
      Indigenous Australian (IA) ( n = 11) and Caucasian ( n = 43) patients,
      respectively ( p < 0.01). There was no significant subgroup difference regarding
      ISN class (proliferative 66%, membranous 19%, mesangial 15%), levels of
      proteinuria (median PCR 300 mg/mmol) or frequency of raised creatinine (31%),
      anti-dsDNA antibody (89%) or hypocomplementaemia (88%). Treatment included
      corticosteroids (91%), cyclophosphamide (30%), mycophenolate (67%) and
      antihypertensive drugs (67%). Five- (81%) and 10-year (70%) survival was lower
      for IAs than for Caucasians and Asians (95% each at both time points) ( p =
      0.016). Five- and 10-year renal survival (endpoint renal replacement therapy
      (RRT)) was 86% and 64% for IA vs 100% for Asian, 100% and 96% for Caucasian
      patients ( p = 0.02). IA background was the only independent predictor for poor
      patient survival and together with male gender also for renal survival. Only 25%
      of all patients remained free of any organ damage with non-renal damage observed
      in 53% of survivors. Conclusions LN incidence in WA was 0.75/100,000 with the
      lowest rate observed in Caucasians. While Asian patients have the same favourable
      outlook as Caucasians, the outcome is much bleaker for IA patients. Other
      clinical and histological findings did not predict outcomes, and importantly more
      than half of all surviving patients accrued non-renal damage.

PMID- 30092735
TI  - Cell Phone Use and Happiness Among Chinese Older Adults: Does Rural/Urban
      Residence Status Matter?
AB  - This study explores the relationship between cell phone use and self-reported
      happiness among older adults in Mainland China and whether rural/urban residence
      status moderates this relationship. The analysis is based on a sample of 6,952
      respondents over the age of 60, from the 2010 wave of China Family Panel Studies.
      Findings show that using own cell phone is positively associated with self
      reported happiness among Chinese older adults (odds ratio [ OR] = 1.283, p <
      .001). This relationship remains for respondents residing in rural areas ( OR =
      1.616, p < .01) but not for their urban counterparts. Findings reflect on how the
      happiness of Chinese older adults has been affected by a growing shift in the
      traditional family values due to the unprecedented economic growth. Results also
      highlight the disparities between state support for older adults in rural and
      urban areas as well as the necessity to develop relevant policies to improve the
      subjective well-being of China's rapidly growing population of older adults.

PMID- 30092737
TI  - Boundary-Spanning Care: Reducing Psychiatric Rehospitalization and Self-Injury in
      a Jail Population.
AB  - Individuals with serious mental illness detained in jail may require frequent
      psychiatric hospitalization due to the destabilizing nature of the jail
      environment. This study examined the impact of a pilot treatment program
      involving continuity of patient care across jail and hospital settings aimed at
      reducing hospitalizations and negative health outcomes for a population of high
      risk, incarcerated individuals with mental illness. This study examined rate
      ratios of psychiatric hospitalizations, injuries, and suicide watches, comparing
      15 patients in the treatment program to themselves pretreatment and to a control
      group of 15 frequently rehospitalized patients. Patients in treatment experienced
      significant decreases in overall hospitalizations ( p < .001), 15-day
      rehospitalizations ( p < .002), and suicide watches in jail ( p < .02), compared
      to themselves pretreatment. A boundary-spanning treatment program lowered
      hospitalization rates and need for suicide watch for a small, yet clinically
      complicated and challenging group of patients.

PMID- 30092736
TI  - Clinical subsets of juvenile dermatomyositis classified by myositis-specific
      autoantibodies: Experience at a single center in Japan.
AB  - OBJECTIVES: This study investigated the association between myositis-specific
      autoantibodies (MSAs) and clinical subsets of juvenile dermatomyositis (JDM) in
      Japanese patients. METHODS: Twenty-one patients at a single center who developed
      initial or relapsed JDM from 2011 to 2016 were analyzed. Serum concentrations of
      MSAs against TIF1-gamma, MDA5, NXP2, Mi-2, ARS, and SAE were measured by enzyme
      linked immunosorbent assays. Clinical symptoms and laboratory data were obtained
      from clinical records. Clinical characteristics were compared in patients with
      autoantibodies against TIF1-gamma, MDA5, and NXP2. RESULTS: Of the 21 patients,
      20 (95.2%) were positive for one or more MSAs, including nine (42.9%), five
      (23.8%), six (28.6%), and one (4.8%) positive for anti-TIF1-gamma, anti-MDA5,
      anti-NXP2, and anti-Mi-2 autoantibodies. No patient was positive for anti-ARS or
      anti-SAE autoantibodies. The frequency of diffuse cutaneous lesions was higher in
      patients with anti-TIF1-gamma autoantibodies. Anti-MDA5 autoantibody-positive
      patients had features of interstitial lung disease on chest computed tomography.
      Severe muscle damage at disease onset was significantly associated with
      positivity for anti-NXP2 autoantibodies. CONCLUSION: Similar to findings in
      Western countries, the clinical characteristics of JDM in Japanese may differ for
      each type of MSAs.

PMID- 30092738
TI  - Impact of MAGNET hospital designation on nursing culture: an integrative review.
AB  - BACKGROUND: Organisational culture is a critical part of a positive and
      productive working environment and often presents as an area of ongoing
      development. The MAGNET recognition program awards recognition to organisations
      that have positive organisational cultures that meet the standards and criteria.
      However, the broad impact of MAGNET on hospital culture outside of America
      remains unclear. OBJECTIVE: In this study, we explore the impact of MAGNET
      designation on organisational culture within the nursing context. METHODS: An
      integrative literature review was performed using a systematic search of Medline
      (Ovid), Embase (Elsevier) and the Cumulative Index to Nursing and Allied Health
      Literature (CINAHL Ebsco) databases and a combination of subject headings and key
      words for organizational culture, organizational change and MAGNET hospital, as
      well as reference chaining was conducted. Using a constant comparative process
      key categories, themes and subthemes emerged. RESULTS: Twenty-nine key studies
      were identified and were evaluated utilising two study quality appraisal tools;
      National Health and Medical Research Council (NH&MRC) levels of evidence and the
      Polit and Beck critical appraisal tool. Three key categories emerged from the
      data: (1) nurse practice environment; (2) structure and process models; (3)
      measurement scales. A key finding was that MAGNET designation appears to enhance
      organisational culture for nurses and the framework used to introduce MAGNET
      helps to empower nurses to direct organisational culture in their facility.
      Conclusion and Implications for Nursing and Health Policy: MAGNET appears to have
      a positive impact on organisational culture, particularly for nurses. However,
      lack of standardised evaluation tools used to assess organisational culture
      associated with MAGNET designation limits comparability of the studies.
      Generally, the quality of evidence used to develop recommendations was poor to
      very poor. More, well designed studies undertaken outside of the USA are
      required. Impact Statement: An in-depth integrative review exploring the impact
      of MAGNET designation on organisational culture has not been undertaken. In this
      paper, we have used an integrative review methodology to identify, examine,
      thematically group and critically evaluate published literature around the impact
      of MAGNET designation on organisational culture within designated hospitals.

PMID- 30092740
TI  - Letter to the Editor Regarding "Spontaneous Findings in the Eyes of Cynomolgus
      Monkeys ( Macaca fascicularis) of Mauritian Origin" by Woicke et al. ( Toxicol
      Pathol 46, 273-282, 2018).

PMID- 30092739
TI  - False memories in obstructive sleep apnoea syndrome: evidence from the divided
      attention paradigm at encoding or retrieval.
AB  - Patients with obstructive sleep apnoea syndrome (OSAS) exhibit impaired retrieval
      of item-specific information, increasing their propensity to generate false
      recognitions. The present study investigated the effect of OSAS on false
      recognition, using a divided-attention paradigm to examine whether reducing the
      availability of attentional resources during encoding or retrieval in healthy
      participants mimics the effect of OSAS. We tested four groups of participants,
      using the Deese - Roediger - McDermott paradigm: patients with OSAS and controls,
      either under full attention or under divided attention at encoding or retrieval.
      Results showed that divided attention at retrieval, but not at encoding, mimicked
      the effects of OSAS on memory performance, as controls in this group exhibited a
      higher level of false recognition than those under full attention, but a similar
      level of correct recognition. Our results suggest that the greater susceptibility
      of patients with OSAS to false recognition may be due to a limited availability
      of attentional resources, which may specifically disrupt retrieval processes.

PMID- 30092741
TI  - A hybrid process for 2,4-dichlorophenoxy acetic acid herbicidal treatment and its
      microbial identification by MALDI-TOF mass spectrometry.
AB  - The feasibility of coupling photocatalysis and a biological treatment to remove a
      herbicide - 2,4-dichlorophenoxy acetic acid (2,4-D) - from pure water was
      examined using batch experiments following three protocols: aerated (A-BR) and
      non-aerated biodegradation (NA-BR) alone, and intimately combined
      photodegradation and biodegradation (P-B). In view of a subsequent biological
      treatment, 15 and 180 min irradiation times were chosen in accordance with
      spectrophotometric and LC-MS/MS results that indicated the decrease in the
      COD/TOC ratio during photocatalysis. Pre-treatment led to a quick decrease in
      concentration of 2,4-D and COD during the biological process: a 78.79 +/- 0.30%
      COD removal and 38.23 +/- 3.12% 2,4-D elimination was measured after 5760 min in
      A-BR, and 80.89 +/- 0.81% COD and 81.36 +/- 1.37% 2,4-D removal was achieved
      after 2880 min in P-B. For species identification using matrix-assisted laser
      desorption/ionization (MALDI)-time of flight (TOF)-TOF/MS equipment, Aeromonas
      eucrenophila, Stenotrophomonas acidaminiphila, Ralstonia pickettii,
      Sphingobacterium multivorum and Acinetobacter towneri were identified with high
      accuracy, and they play important roles in the degradation of 2,4-D.

PMID- 30092743
TI  - Erratum.

PMID- 30092742
TI  - Potential role of rituximab in metastatic castrate-resistant prostate cancer.
AB  - Nearly all men with prostate cancer who are treated with androgen deprivation
      therapy develop disease progression. There is considerable evidence to suggest
      that CXCL 13 released by tumor cells leads to B-cell infiltration into the
      prostate cells. This B-cell infiltration has been postulated to play a role in
      development of disease progression following androgen-deprivation therapies. We
      present a case of a patient who achieved remission of metastatic castrate
      resistant prostate cancer after receiving rituximab and bendamustine for the
      treatment of follicular lymphoma. The findings in this report suggest that
      further investigation is warranted for utilizing B-cell targeted therapy in
      delaying progression of castrate-resistant prostate cancer.

PMID- 30092744
TI  - Changes in Vasodilator-Stimulated Phosphoprotein Phosphorylation, Profilin-1, and
      Cofilin-1 in Accreta and Protection by DHA.
AB  - Accreta and gestational trophoblastic disease (ie, choriocarcinoma) are placental
      pathologies characterized by hyperproliferative and invasive trophoblasts.
      Cellular proliferation, migration, and invasion are heavily controlled by actin
      binding protein (ABP)-mediated actin dynamics. The ABP vasodilator-stimulated
      phosphoprotein (VASP) carries key regulatory role. Profilin-1, cofilin-1, and
      VASP phosphorylated at Ser157 (pVASP-S157) and Ser239 (pVASP-S239) are ABPs that
      regulate actin polymerization and stabilization and facilitate cell metastases.
      Docosahexaenoic acid (DHA) inhibits cancer cell migration and proliferation. We
      hypothesized that analogous to malignant cells, ABPs regulate these processes in
      extravillous trophoblasts (EVTs), which exhibit aberrant expression in placenta
      accreta. Placental-myometrial junction biopsies of histologically confirmed
      placenta accreta had significantly increased immunostaining levels of cofilin-1,
      VASP, pVASP-S239, and F-actin. Treatment of choriocarcinoma-derived trophoblast
      (BeWo) cells with DHA (30 uM) for 24 hours significantly suppressed
      proliferation, migration, and pVASP-S239 levels and altered protein profiles
      consistent with increased apoptosis. We concluded that in accreta changes in the
      ABP expression profile were a response to restore homeostasis by counteracting
      the hyperproliferative and invasive phenotype of the EVT. The observed
      association between VASP phosphorylation, apoptosis, and trophoblast
      proliferation and migration suggest that DHA may offer a therapeutic solution for
      conditions where EVT is hyperinvasive.

PMID- 30092745
TI  - Catechol biodegradation by a novel hybrid anoxic biofilter.
AB  - In this study, simultaneous catechol biodegradation and nitrate removal were
      successfully achieved in a hybrid anoxic biofilter (HAB). The maximum
      biodegradation concentration of catechol by HAB, was determined 1,000 mg/L.
      However, optimum conditions of HAB for biodegradation of catechol were determined
      in catechol and nitrate concentrations of 750 mg/L and 140 mg/L-N, respectively,
      and a hydraulic retention time of 18 h, which corresponded to organic loading
      rate of 1.89 kg COD/m3. d and COD/N of 2.32. The low COD/N ratio is related to
      nitrogen cycling and reflected N2O flux within denitrification biofilters. Due to
      the use of a biofilter in this process, despite the concentration of MLSS above
      3000 mg/L in the suspended growth section, HAB was capable of producing effluent
      with low turbidity (0.8 +/- 0.5 NTU), without the need for any secondary
      sedimentation basin. Therefore, HAB process offers an efficient way for
      wastewater treatment with high concentration of aromatic compounds and nitrate in
      anoxic conditions and providing environmental standards for wastewater discharge.

PMID- 30092746
TI  - Insights on inhibition of Plasmodium falciparum plasmepsin I by novel
      epoxyazadiradione derivatives - molecular docking and comparative molecular field
      analysis.
AB  - In the present study, we have explored the anti-malarial potential of
      epoxyazadiradione, the natural entity extracted from the neem seed oil and its
      chemical derivatives, against Plasmodium falciparum. The Surflex dock analysis of
      41 compounds against an indispensable target, plasmepsin I (PM-I) revealed that
      around 70% of the compounds are found to have good binding capacity with the
      consensus score (C-score) of 5 to 4 with few hydrogen bonds. To elucidate the
      major structural requirements, vital for binding with the plasmepsin enzyme and
      to develop the predictive models, three-dimentional quantitative structural
      activity relationship (3D-QSAR) - comparative molecular field analysis (CoMFA)
      was carried out using Sybyl X.0. Robust and predictive models were obtained with
      cross-validated correlation coefficient (q2) value of 0.967 and the non-cross
      validated correlation coefficient (r2) value of 0.825, which were validated by an
      external test set with the predictive correlation coefficient r2(pred) values of
      0.773. Three zones were identified for substitution with bulky groups and one
      zone for substitution with non-bulky groups. Three positions favouring the
      electronegative group substitution and one for the electropositive group
      substitution were identified. The physicochemical properties of ligands with the
      highest C-score were studied. Communicated by Ramaswamy H. Sarma.

PMID- 30092748
TI  - Stenosis Caused by Suture-Mediated Vascular Closure Device in an Angiographic
      Normal Common Femoral Artery: Its Mechanism and Management.
AB  - Vascular closing devices (VCDs) are widely used to replace manual compression at
      the femoral puncture site and to reduce the discomfort of patients undergoing
      percutaneous coronary procedure by shortening bed rest. Among the vascular
      complications related to these devices, the femoral artery stenosis or occlusion
      is rarely reported, and its standard management is not well established. We
      report a case of symptomatic femoral artery stenosis caused by suture-mediated
      VCD and managed using rotational atherectomy device and balloon angioplasty. In
      addition, we propose the possible mechanisms for this complication.

PMID- 30092747
TI  - Experience: developing an inpatient malnutrition checklist for children 6 to 59
      months to improve WHO protocol adherence and facilitate quality improvement in a
      low-resource setting.
AB  - In low-resource settings, inpatient case fatality for severe acute malnutrition
      (SAM) remains high despite evidenced-based protocols and resources to treat SAM.
      Key reasons include a combination of insufficiently trained staff, poor teamwork
      and inadequate compliance to WHO treatment guidelines which are proven to reduce
      mortality. Checklists have been used in surgery and obstetrics to ameliorate
      similarly complicated yet repetitive work processes and may be a key strategy to
      improving inpatient SAM protocol adherence and reducing unnecessary death. Here,
      we share our experience developing and piloting an inpatient malnutrition
      checklist (MLNC) for children 6 to 59 months and associated scoring system to
      coordinate care delivery, improve team documentation, strengthen WHO malnutrition
      protocol adherence and facilitate quality improvement in a district hospital in
      rural Rwanda. MLNC was developed after careful review of the 2009 Rwandan
      National Nutrition Protocol and 2013 WHO malnutrition guidelines. Critical steps
      were harmonized, extracted and designed into an initial MLNC with input from
      pediatric ward nurses, doctors, a locally based pediatrician and a registered
      dietitian. A scoring system was developed to facilitate quality improvement.
      Using the standard Plan-Do-Study-Act cycle, MLNC was modified and progress
      assessed on a monthly to bimonthly basis. Significant modifications occurred in
      the first 6 months of piloting including incorporation of treatment reminders and
      formatting improvements, as well as initiation of the MLNC from the emergency
      department. The MLNC is the first checklist to be developed that unifies WHO 10
      steps of treatment of inpatient SAM with local standards. Anecdotally, MLNC was
      observed to identify gaps in key malnutrition care, promote protocol adherence
      and facilitate quality improvement. Data gathering on the MLNC local facility
      impact is underway. Collaborative international efforts are needed to create an
      inpatient malnutrition checklist for wider use to improve quality and reduce
      unnecessary, facility-based child mortality.

PMID- 30092749
TI  - Multifocal pelvic osteomyelitis in a child associated with a cat-scratch disease:
      a case report and review of the literature.
AB  - Bone infections in cat-scratch disease (CSD) are uncommon and the diagnosis can
      be missed. A 3-year-old boy with multifocal pelvic osteomyelitis caused by
      Bartonella henselae is reported. Serological tests were negative but DNA was
      detected by polymerase chain reaction assay of a lymph node. A swift recovery
      followed antibiotic treatment and there was completeresolution within a few
      months. The literature on 64 cases of osteomyelitis owing to CSD in children and
      adults since 1954 is reviewed.

PMID- 30092751
TI  - Safety of cannabidiol prescribed for children with refractory epilepsy.

PMID- 30092750
TI  - Relative survival of patients with lymphoma in Queensland according to
      histological subtype.
AB  - OBJECTIVE: To evaluate relative survival of patients in Queensland with different
      lymphoma subtypes; to determine whether outcomes have improved with recent
      changes in treatment; to evaluate relative survival according to place of
      residence and socio-economic status. DESIGN: Retrospective population-based
      study; analysis of data from the Oncology Analysis System, an online reporting
      tool for cancer incidence and outcomes in Queensland. PARTICIPANTS: Patients over
      15 years of age diagnosed with lymphoma in Queensland during 1993-2012. MAIN
      OUTCOME MEASURES: Relative survival by lymphoma subtype; influence of place of
      residence and socio-economic status, age group, sex, year of diagnosis (in 5-year
      bands), and Pharmaceutical Benefits Scheme funding of rituximab for treating B
      cell lymphomas on relative survival. RESULTS: 9509 people (56% men) were
      diagnosed with lymphoma during 1993-2012. Five-year relative survival improved
      significantly between 1993-1997 and 2008-2012 for patients with diffuse large B
      cell lymphoma (47%; 95% CI, 42-51% v 64%; 95% CI, 61-67%) or follicular lymphoma
      (62%; 95% CI, 57-66% v 88%; 95% CI, 85-90%; each P < 0.001). Rituximab became
      available for treating these subtypes during 2003-2006. There was no change in
      relative survival for patients with Hodgkin lymphoma (81%; 95% CI, 76-85% v 80%;
      95% CI, 75-84%; P = 0.22). The only statistically significant difference
      according to place of residence or socio-economic status was inferior relative
      survival for rural residents with diffuse large B-cell lymphoma (hazard ratio,
      1.14; 95% CI, 1.01-1.28). CONCLUSION: Relative survival for patients with B-cell
      non-Hodgkin lymphoma improved significantly with the introduction of rituximab as
      first-line therapy in Australia.

PMID- 30092752
TI  - Medicinal cannabis in Australia, 2016: the Cannabis as Medicine Survey (CAMS-16).
AB  - OBJECTIVE: To explore patterns of cannabis use for medical purposes in Australia
      immediately prior to the 2016 legislation for frameworks for medical cannabis
      use. Design, setting: Anonymous online survey with convenience sample, April
      October 2016. Participants were recruited through online media and at
      professional and consumer forums. PARTICIPANTS: Adults (at least 18 years of age)
      who reported using a cannabis product for self-identified medical or therapeutic
      reasons during the preceding 12 months. MAIN OUTCOME MEASURES: Consumer
      characteristics; indications and patterns of medical cannabis use; perceived
      benefits and harms; views on appropriate availability of medical cannabis.
      RESULTS: Most of the 1748 participants were men (68.1%) and employed (56.6%),
      with a mean age of 37.9 years (SD, 13.4 years) and mean reported period of
      medical cannabis use of 9.8 years (SD, 12.5 years). The most frequent reasons for
      medical cannabis use were anxiety (50.7%), back pain (50.0%), depression (49.3%),
      and sleep problems (43.5%). Respondents had used medical cannabis on a mean of
      19.9 of the previous 28 days (SD, 10.0 days), spending a mean $68.60 (SD, $85.00)
      per week, and 83.4% had inhaled the substance. Participants reported high levels
      of clinical effectiveness and frequent side effects, including drowsiness, ocular
      irritation, lethargy and memory impairment; 17% met DSM-5 criteria for moderate
      or severe cannabis use disorder. Many reported harms or concerns related to the
      illicit status of cannabis. Participants believed that medical cannabis should be
      integrated into mainstream health care, and that products should be required to
      meet consistency and safety standards. CONCLUSION: Illicitly sourced cannabis is
      used to treat a broad range of medical conditions in Australia. Future models of
      prescribed medical cannabis take consumer patterns of use and demand into
      consideration.

PMID- 30092753
TI  - Cannabidiol for treating drug-resistant epilepsy in children: the New South Wales
      experience.
AB  - OBJECTIVE: To evaluate the tolerability and safety of cannabidiol for treating
      drug-resistant epilepsy in children, and to describe adverse events associated
      with such treatment. STUDY DESIGN: Prospective, open label cohort study. SETTING:
      Three tertiary NSW referral centres with paediatric neurology services.
      PARTICIPANTS: First 40 children enrolled in the NSW Compassionate Access Scheme
      for children with drug-resistant epilepsy and uncountable daily seizures.
      INTERVENTION: Children received cannabidiol as an adjunct anti-epileptic drug,
      titrated to a maximum of 25 mg/kg/day, for up to 12 weeks. OUTCOME MEASURES:
      Adverse events, withdrawals, and caregiver and physician Global Impression of
      Change assessments were recorded at 4, 8 and 12 weeks. Seizure frequency could
      not be reliably recorded because of disease severity. RESULTS: Thirty-nine
      patients reported at least one adverse event; many were deemed unrelated to
      cannabidiol treatment. The most frequent treatment-related adverse event was
      somnolence (15 participants), which resolved spontaneously in ten patients; it
      was particularly frequent in patients taking higher clobazam doses.
      Gastrointestinal effects (nausea, vomiting, diarrhoea) were each reported by
      seven to nine participants. Four children were withdrawn from treatment,
      including one with elevated transaminase levels. The caregivers of 12 children
      felt the overall health of their children had much or very much improved;
      clinicians assessed seven children as being much or very much improved.
      CONCLUSION: Cannabidiol as an adjunct treatment had some subjective benefit for
      overall health, with a manageable adverse event profile. Monitoring changes in
      liver function and awareness of potential drug interactions is essential. Whether
      the reported benefit is attributable to cannabidiol cannot be established in an
      open label study of participants with severe intractable epilepsy.

PMID- 30092755
TI  - REHUNT: a reliable and open source package for restriction enzyme hunting.
AB  - BACKGROUND: Restriction enzymes are used frequently in biotechnology. However,
      manual mining of restriction enzymes is challenging. Furthermore, integrating
      available restriction enzymes into different bioinformatics systems is necessary
      for many biotechnological applications, such as polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). Thus, in the present study,
      we developed the package REHUNT (Restriction Enzymes HUNTing), which mines
      restriction enzymes from the public database REBASE using a series of search
      operations. RESULTS: REHUNT is a reliable and open source package implemented in
      JAVA. It provides useful methods and manipulations for biological sequence
      analysis centered around restriction enzymes contained in REBASE. All available
      restriction enzymes for the imported biological sequences can be identified by
      REHUNT. Different genotypes can be identified using PCR-RFLP based on REHUNT for
      single nucleotide polymorphism (SNP), mutations, and the other variations. REHUNT
      robustly recognizes multiple inputs with different formats, e.g. regular DNA
      sequences, variation-in-sequence indicated by IUPAC code, as well as variation-in
      sequence indicated by dNTPs format. Variations including di-, tri-, and tetra
      allelic types and indel formats are also acceptable. Furthermore, REHUNT provides
      classified restriction enzymes output, including IUPAC and general sequence
      types, as well as commercial and non-commercial availabilities. REHUNT also
      enables analysis for high throughput screening (HTS) technologies. CONCLUSIONS:
      REHUNT is open source software with GPL v3 license and can be run on all
      platforms. Its features include: 1) Quick restriction enzymes search throughout a
      sequence based on the Boyer-Moore algorithm; 2) all available restriction enzymes
      provided and regularly updated from REBASE; 3) an open source API available of
      integrating all types of bioinformatics systems and applications; 4) SNP
      genotyping available for plant and animal marker-assisted breeding, and for human
      genetics; and 5) high throughput analysis available for Next Generation
      Sequencing (NGS). REHUNT not only to effectively looks for restriction enzymes in
      a sequence, but also available for SNP genotyping. Furthermore, it can be
      integrated into other biological and medical applications. REHUNT offers a
      convenient and flexible package for powerful restriction enzymes analyses in
      association studies, and supports high throughput analysis. The source codes and
      complete API documents are available at SourceForge:
      https://sourceforge.net/projects/rehunt/ , GitHub:
      https://github.com/yuhuei/rehunt , and at:
      https://sites.google.com/site/yhcheng1981/rehunt .

PMID- 30092756
TI  - Putative candidate genes responsible for leaf rolling in rye (Secale cereale L.).
AB  - BACKGROUND: Rolling of leaves (RL) is a phenomenon commonly found in grasses.
      Morphology of the leaf is an important agronomic trait in field crops especially
      in rice; therefore, majority of the rice breeders are interested in RL. There are
      only few studies with respect to RL of wheat and barley; however, the information
      regarding the genetic base of RL with respect to the shape of leaf in rye is
      lacking. To the best of our knowledge, this is the first study on the
      localization of loci controlling RL on high density consensus genetic map of rye.
      RESULTS: Genotypic analysis led to the identification of 43 quantitative trait
      loci (QTLs) for RL, grouped into 28 intervals, which confirms the multigenic base
      of the trait stated for wheat and rice. Four stable QTLs were located on
      chromosomes 3R, 5R, and 7R. Co-localization of QTL for RL and for different
      morphological, biochemical and physiological traits may suggests pleiotropic
      effects of some QTLs. QTLs for RL were associated with QTLs for such
      morphological traits as: grain number and weight, spike number per plant,
      compactness of spike, and plant height. Two QTLs for RL were found to coincide
      with QTLs for drought tolerance (4R, 7R), two with QTLs for heading earliness
      (2R, 7R), one with alpha-amylase activity QTL (7R) and three for pre-harvest
      sprouting QTL (1R, 4R, 7R). The set of molecular markers strongly linked to RL
      was selected, and the putative candidate genes controlling the process of RL were
      identified. Twelve QTLs are considered as linked to candidate genes on the base
      of DArT sequences alignment, which is a new information for rye. CONCLUSIONS: Our
      results expand the knowledge about the network of QTLs for different
      morphological, biochemical and physiological traits and can be a starting point
      to studies on particular genes controlling RL and other important agronomic
      traits (yield, earliness, pre-harvest sprouting, reaction to water deficit) and
      to appoint markers useful in marker assisted selection (MAS). A better knowledge
      of the rye genome and genes could both facilitate rye improvement itself and
      increase the efficiency of utilizing rye genes in wheat breeding.

PMID- 30092757
TI  - Association of glycemic status and segmental left ventricular wall thickness in
      subjects without prior cardiovascular disease: a cross-sectional study.
AB  - BACKGROUND: Left ventricular (LV) hypertrophy and changes in LV geometry are
      associated with increased cardiovascular mortality. Subjects with type 2 diabetes
      have an increased risk of such alterations in cardiac morphology. We sought to
      assess the association of glycemic status and LV wall thickness measured by
      cardiac magnetic resonance (CMR), and potential interactions of hypertension and
      diabetes. METHODS: CMR was performed on 359 participants from a cross-sectional
      study nested in a population-based cohort (KORA FF4) free of overt cardiovascular
      disease. Participants were classified according to their glycemic status as
      either control (normal glucose metabolism), prediabetes or type 2 diabetes.
      Segmentation of the left ventricle was defined according to the American Heart
      Association (AHA) 16-segment model. Measurements of wall thickness were obtained
      at end-diastole and analyzed by linear regression models adjusted for traditional
      cardiovascular risk factors. RESULTS: LV wall thickness gradually increased from
      normoglycemic controls to subjects with prediabetes and subjects with diabetes
      (8.8 +/- 1.4 vs 9.9 +/- 1.4 vs 10.5 +/- 1.6 mm, respectively). The association
      was independent of hypertension and traditional cardiovascular risk factors (beta
      coefficient: 0.44 mm for prediabetes and 0.70 mm for diabetes, p-values compared
      to controls: p = 0.007 and p = 0.004, respectively). Whereas the association of
      glycemic status was strongest for the mid-cavity segments, the association of
      hypertension was strongest for the basal segments. CONCLUSION: Abnormal glucose
      metabolism, including pre-diabetes, is associated with increased LV wall
      thickness independent of hypertension.

PMID- 30092759
TI  - Multi-class segmentation of neuronal structures in electron microscopy images.
AB  - BACKGROUND: Serial block face scanning electron microscopy (SBFEM) is becoming a
      popular technology in neuroscience. We have seen in the last years an increasing
      number of works addressing the problem of segmenting cellular structures in SBFEM
      images of brain tissue. The vast majority of them is designed to segment one
      specific structure, typically membranes, synapses and mitochondria. Our
      hypothesis is that the performance of these algorithms can be improved by
      concurrently segmenting more than one structure using image descriptions obtained
      at different scales. RESULTS: We consider the simultaneous segmentation of two
      structures, namely, synapses with mitochondria, and mitochondra with membranes.
      To this end we select three image stacks encompassing different SBFEM acquisition
      technologies and image resolutions. We introduce both a new Boosting algorithm to
      perform feature scale selection and the Jaccard Curve as a tool compare several
      segmentation results. We then experimentally study the gains in performance
      obtained when simultaneously segmenting two structures with properly selected
      image descriptor scales. The results show that by doing so we achieve significant
      gains in segmentation accuracy when compared to the best results in the
      literature. CONCLUSIONS: Simultaneously segmenting several neuronal structures
      described at different scales provides voxel classification algorithms with
      highly discriminating features that significantly improve segmentation accuracy.

PMID- 30092760
TI  - Decomposing socioeconomic inequalities in alcohol use by men living in South
      African urban informal settlements.
AB  - BACKGROUND: The prevalence of alcohol consumption among males living in urban
      settlements in South Africa is high. This paper aims to measure socioeconomic
      inequalities in alcohol use among men residing in informal settlements and also
      to examine the factors associated with inequality in alcohol use among men living
      in informal settlements. METHODS: The study uses data from the 2016 Study of
      South African Informal Settlements. Multiple correspondence analysis is used to
      calculate a wealth index as a measure of socioeconomic status. The Erreygers
      concentration index is employed to quantify the degree of socioeconomic
      inequality in alcohol use and decomposition analysis is conducted to assess the
      factors associated with inequality in alcohol use by men of various age groups.
      RESULTS: There is a socioeconomic-related inequality in alcohol use in informal
      settlements that discriminates against poor men. Inequality is especially
      pronounced in the case of males aged 15-34 years and males aged 35-44 years.
      Wealth status makes the biggest contribution to socioeconomic inequality in
      alcohol use. The contribution of social determinants of health like marital
      status and employment status differ across age groups. Employment status
      contribute more to the alcohol use inequality among males aged 15-34 years while
      marital status contribute more to the alcohol use inequality among males aged 35
      44 years. Being single substantially increases inequality in alcohol use.
      CONCLUSION: Inequality in alcohol use exists among both younger and older males
      and discriminate against the poor. Public policies aimed at promoting public
      health and the prevention of unhealthy behaviours should target younger and
      middle-aged men from socioeconomically disadvantaged groups. We also suggest
      policies that target single males in informal settlements.

PMID- 30092758
TI  - RNA-seq highlights parallel and contrasting patterns in the evolution of the
      nuclear genome of fully mycoheterotrophic plants.
AB  - BACKGROUND: While photosynthesis is the most notable trait of plants, several
      lineages of plants (so-called full heterotrophs) have adapted to obtain organic
      compounds from other sources. The switch to heterotrophy leads to profound
      changes at the morphological, physiological and genomic levels. RESULTS: Here, we
      characterize the transcriptomes of three species representing two lineages of
      mycoheterotrophic plants: orchids (Epipogium aphyllum and Epipogium roseum) and
      Ericaceae (Hypopitys monotropa). Comparative analysis is used to highlight the
      parallelism between distantly related fully heterotrophic plants. In both
      lineages, we observed genome-wide elimination of nuclear genes that encode
      proteins related to photosynthesis, while systems associated with protein import
      to plastids as well as plastid transcription and translation remain active. Genes
      encoding components of plastid ribosomes that have been lost from the plastid
      genomes have not been transferred to the nuclear genomes; instead, some of the
      encoded proteins have been substituted by homologs. The nuclear genes of both
      Epipogium species accumulated nucleotide substitutions twice as rapidly as their
      photosynthetic relatives; in contrast, no increase in the substitution rate was
      observed in H. monotropa. CONCLUSIONS: Full heterotrophy leads to profound
      changes in nuclear gene content. The observed increase in the rate of nucleotide
      substitutions is lineage specific, rather than a universal phenomenon among non
      photosynthetic plants.

PMID- 30092754
TI  - Dietary phytochemicals in breast cancer research: anticancer effects and
      potential utility for effective chemoprevention.
AB  - Cancerous tissue transformation developing usually over years or even decades of
      life is a highly complex process involving strong stressors damaging DNA, chronic
      inflammation, comprehensive interaction between relevant molecular pathways, and
      cellular cross-talk within the neighboring tissues. Only the minor part of all
      cancer cases are caused by inborn predisposition; the absolute majority carry a
      sporadic character based on modifiable risk factors which play a central role in
      cancer prevention. Amongst most promising candidates for dietary supplements are
      bioactive phytochemicals demonstrating strong anticancer effects. Abundant
      evidence has been collected for beneficial effects of flavonoids, carotenoids,
      phenolic acids, and organosulfur compounds affecting a number of cancer-related
      pathways. Phytochemicals may positively affect processes of cell signaling, cell
      cycle regulation, oxidative stress response, and inflammation. They can modulate
      non-coding RNAs, upregulate tumor suppressive miRNAs, and downregulate oncogenic
      miRNAs that synergically inhibits cancer cell growth and cancer stem cell self
      renewal. Potential clinical utility of the phytochemicals is discussed providing
      examples for chemoprevention against and therapy for human breast cancer. Expert
      recommendations are provided in the context of preventive medicine.

PMID- 30092761
TI  - An elderly patient presenting with a primary spinal multifocal intradural
      extramedullary pilocytic astrocytoma: a case report and review of the literature.
AB  - BACKGROUND: Pilocytic astrocytoma is a low-grade central nervous system tumor
      most commonly seen in children. Dissemination from a primary intracranial tumor
      along the neuroaxis has been described at both presentation and disease
      progression. However, the development of an intradural extramedullary pilocytic
      astrocytoma independent of a primary intraparenchymal tumor in an adult patient
      with no history of pilocytic astrocytoma has rarely been reported. CASE
      PRESENTATION: A 69-year-old woman presented with progressive myelopathic symptoms
      and thoracic radicular pain. MRI imaging of the whole spine showed an enhancing
      intradural extramedullary lesion extending from the cervical cord to T11 causing
      cord compression. Laminectomies were performed for surgical decompression and
      histopathology was consistent with pilocytic astrocytoma. Complete staging was
      done that included imaging of the brain and cerebrospinal fluid cytology. No
      other tumor was found by these methods. Postoperatively the patient was treated
      with large field spinal radiation and concurrent chemotherapy followed by
      adjuvant chemotherapy. She has thus far been clinically and radiographically
      stable. CONCLUSION: This is a rare case of an adult with multiple spinal
      pilocytic astrocytomas in an intradural extramedullary location, typically the
      result of cerebrospinal fluid dissemination of neoplastic cells from a primary
      intracranial tumor site (i.e. drop metastasis). No conventional primary tumor was
      identified in this patient, suggesting these tumors may arise from heterotopic
      gliomas.

PMID- 30092763
TI  - A cross-sectional exploratory analysis between pet ownership, sleep, exercise,
      health and neighbourhood perceptions: the Whitehall II cohort study.
AB  - BACKGROUND: To explore associations between pets, and specifically dog ownership
      and sleep, health, exercise and neighbourhood. METHODS: Cross sectional
      examination of 6575 participants of the Whitehall II study aged between 59 and 79
      years. We used self-assessed measurement scales of the Short Form (SF36), General
      Health Questionnaire (GHQ), Control, Autonomy, Self-realisation and Pleasure
      (CASP), Centre for Epidemiologic Studies Depression Scale (CES-D), sleep,
      exercise, and perceptions of local neighbourhood. In addition the Mini Mental
      State Examination which is administered to test global cognitive status (MMSE).
      RESULTS: We found 2/7 people owned a pet and of those 64% were "very" attached to
      their pet. Mild exercise in metabolic equivalents (MET-hours) was significantly
      higher in pet owners than non-owners (median 27.8 (IQR 18.1 to 41.8) vs 25.7 (IQR
      16.8 to 38.7), p = 0.0001), and in dog owners than other pets (median 32.3 (IQR
      20.8 to 46.1) vs 25.6 (IQR 16.8 to 38.5), p < 0.0001). Moderate exercise was also
      significantly higher in pet owners than non pet owners (median 11.8 (IQR 4.2 to
      21.9) vs 9.8 (IQR 2.8 to 19.5), p < 0.0001), and dog owners than owners of other
      pets (median 12.3 (IQR 4.2 to 22.2) vs 10.1 (3.1 to 20.0), p = 0.0002) but there
      were no significant differences with vigorous exercise. We found that pet owners
      were significantly more positive about their neighbourhood than non-owners on 8/9
      questions, while dog owners were (significantly) even more positive than owners
      of other pets on 8/9 questions. Associations with sleep were mixed, although dog
      owners had less trouble falling asleep than non-dog owners, with borderline
      statistical significance. CONCLUSION: Dog owners feel more positive about their
      neighbourhood, do more exercise, and fall asleep more easily than non-dog owners.
      These results suggest that dog owners could be more likely to exercise by walking
      their dogs and therefore may be more familiar and positive about the area in
      which they walk their dog.

PMID- 30092762
TI  - Whole genome analyses of CMY-2-producing Escherichia coli isolates from humans,
      animals and food in Germany.
AB  - BACKGROUND: Resistance to 3rd-generation cephalosporins in Escherichia coli is
      mostly mediated by extended-spectrum beta-lactamases (ESBLs) or AmpC beta
      lactamases. Besides overexpression of the species-specific chromosomal ampC gene,
      acquisition of plasmid-encoded ampC genes, e.g. blaCMY-2, has been described
      worldwide in E. coli from humans and animals. To investigate a possible
      transmission of blaCMY-2 along the food production chain, we conducted a next
      generation sequencing (NGS)-based analysis of 164 CMY-2-producing E. coli
      isolates from humans, livestock animals and foodstuff from Germany. RESULTS: The
      data of the 164 sequenced isolates revealed 59 different sequence types (STs);
      the most prevalent ones were ST38 (n = 19), ST131 (n = 16) and ST117 (n = 13).
      Two STs were present in all reservoirs: ST131 (human n = 8; food n = 2; animal n
      = 6) and ST38 (human n = 3; animal n = 9; food n = 7). All but one CMY-2
      producing ST131 isolates belonged to the clade B (fimH22) that differed
      substantially from the worldwide dominant CTX-M-15-producing clonal lineage ST131
      O25b clade C (fimH30). Plasmid replicon types IncI1 (n = 61) and IncK (n = 72)
      were identified for the majority of blaCMY-2-carrying plasmids. Plasmid sequence
      comparisons showed a remarkable sequence identity, especially for IncK plasmids.
      Associations of replicon types and distinct STs were shown for IncK and ST57,
      ST429 and ST38 as well as for IncI1 and ST58. Additional beta-lactamase genes
      (blaTEM, blaCTX-M, blaOXA, blaSHV) were detected in 50% of the isolates, and
      twelve E. coli from chicken and retail chicken meat carried the colistin
      resistance gene mcr-1. CONCLUSION: We found isolates of distinct E. coli clonal
      lineages (ST131 and ST38) in all three reservoirs. However, a direct clonal
      relationship of isolates from food animals and humans was only noticeable for a
      few cases. The CMY-2-producing E. coli-ST131 represents a clonal lineage
      different from the CTX-M-15-producing ST131-O25b cluster. Apart from the ST
      driven spread, plasmid-mediated spread, especially via IncI1 and IncK plasmids,
      likely plays an important role for emergence and transmission of blaCMY-2 between
      animals and humans.

PMID- 30092765
TI  - The same modality medical image registration with large deformation and clinical
      application based on adaptive diffeomorphic multi-resolution demons.
AB  - BACKGROUND: Diffeomorphic demons can not only guarantee smooth and reversible
      deformation, but also avoid unreasonable deformation. However, the number of
      iterations which has great influence on the registration result needs to be set
      manually. METHODS: This study proposed a novel method to exploit the adaptive
      diffeomorphic multi-resolution demons algorithm to the non-rigid registration of
      the same modality medical images with large deformation. Firstly an optimized non
      rigid registration framework and the diffeomorphism strategy were used, and then
      a similarity energy function based on the grey value was designed as registration
      metric, lastly termination condition was set based on the variation of this
      metric and iterations can be stopped adaptively. Quantitative analyses based on
      the registration evaluation indexes were conducted to prove the validity of this
      method. RESULTS: Registration result of synthetic image and the same modality MRI
      and CT image was compared with those obtained by other demons algorithms.
      Quantitative analyses demonstrated the proposed method's superiority. Medical
      image with large deformation was produced by rotational distortion and extrusion
      transform, and the same modality image registration with large deformation was
      performed successfully. Quantitative analyses showed that the registration
      evaluation indexes remained stable with an increase in transform strength. This
      method can be also applied to pulmonary medical image registration with large
      deformation successfully, and it showed the clinical application value. The
      influence of different driving forces and parameters on the registration result
      was analysed, and the result demonstrated that the proposed method is effective
      and robust. CONCLUSIONS: This method can solve the non-rigid registration problem
      of the same modality medical image with large deformation showing promise for
      diagnostic pulmonary imaging applications.

PMID- 30092764
TI  - Sociodemographic associations with abnormal estimated glomerular filtration rate
      (eGFR) in a large Canadian city: a cross-sectional observation study.
AB  - BACKGROUND: Chronic kidney disease (CKD) is often asymptomatic in its early
      stages but is indicated and is diagnosed with an estimated glomerular filtration
      rate (eGFR) < 60 ml/min/1.73m2. Certain sociodemographic groups are known to be
      at risk for CKD, but it is unclear if there are strong associations between these
      at risk groups with abnormal eGFR test results in Canada. Using only secondary
      laboratory and Census data, geospatial variation and sociodemographic
      associations with abnormal eGFR result rate were investigated in Calgary,
      Alberta. METHODS: Secondary laboratory data from all adult community patients who
      received an eGFR test result were collected from Calgary Laboratory Service's
      Laboratory Information System, which is the sole supplier of laboratory services
      for the large metropolitan city. Group-level sociodemographic variables were
      inferred by combining laboratory data with the 2011 Canadian Census data. Poisson
      regression and relative risk (RR) were used to calculate associations between
      sociodemographic variables with abnormal eGFR. Geographical distribution of
      abnormal eGFR result rates were analyzed by geospatial analysis using ArcGIS.
      RESULTS: Of the 346,663 adult community patients who received an eGFR test
      result, 28,091 were abnormal (8.1%; eGFR < 60 ml/min/1.73m2). Geospatial analysis
      revealed distinct geographical variation in abnormal eGFR result rates in
      Calgary. Women (RR = 1.11, P < 0.0001), and the elderly (age >= 70 years; P <
      0.0001) were significantly associated with an increased risk for CKD, while
      visible minority Chinese (RR = 0.73, P = 0.0011), South Asians (RR = 0.67, P <
      0.0001) and those with a high median household income (RR = 0.88, P < 0.0001) had
      a significantly reduced risk for CKD. CONCLUSIONS: Presented here are significant
      sociodemographic risk associations, and geospatial clustering of abnormal eGFR
      result rates in a large metropolitan Canadian city. Using solely publically
      available secondary laboratory and Census data, the results from this study
      aligns with known sociodemographic risk factors for CKD, as certain
      sociodemographic variables were at a higher risk for having an abnormal eGFR test
      result, while others were protective in this analysis.

PMID- 30092766
TI  - Fatty acid oxidation is associated with proliferation and prognosis in breast and
      other cancers.
AB  - BACKGROUND: Altered cellular metabolism is a hallmark of cancer but the
      association between utilisation of particular metabolic pathways in tumours and
      patient outcome is poorly understood. We sought to investigate the association
      between fatty acid metabolism and outcome in breast and other cancers. METHODS:
      Cox regression analysis and Gene Set Enrichment Analysis (GSEA) of a gene
      expression dataset from primary breast tumours with well annotated clinical and
      survival information was used to identify genesets associated with outcome. A
      geneset representing fatty acid oxidation (FAO) was then examined in other
      datasets. A doxycycline-inducible breast cancer cell line model overexpressing
      the rate-limiting enzyme in FAO, carnitine palmitoyl transferase 1A (CPT1A) was
      generated and analysed to confirm the association between FAO and cancer
      associated characteristics in vitro. RESULTS: We identified a gene expression
      signature composed of 19 genes associated with fatty acid oxidation (FAO) that
      was significantly associated with patient outcome. We validated this observation
      in eight independent breast cancer datasets, and also observed the FAO signature
      to be prognostic in other cancer types. Furthermore, the FAO signature expression
      was significantly downregulated in tumours, compared to normal tissues from a
      variety of anatomic origins. In breast cancer, the expression of CPT1A was higher
      in oestrogen receptor (ER)-positive, compared to ER-negative tumours and cell
      lines. Importantly, overexpression of CPT1A significantly decreased the
      proliferation and wound healing migration rates of MDA-MB231 breast cancer cells,
      compared to basal expression control. CONCLUSIONS: Our findings suggest that FAO
      is downregulated in multiple tumour types, and activation of this pathway may
      lower cancer cell proliferation, and is associated with improved outcomes in some
      cancers.

PMID- 30092767
TI  - Prognostic value of ocular trauma score for open globe injuries associated with
      metallic intraocular foreign bodies.
AB  - BACKGROUND: The prognostic value of the ocular trauma score (OTS) in patients who
      underwent 23-gauge pars plana vitrectomy (23-G PPV) for surgical removal of
      posterior segment metallic intaocular foreign bodies (IOFB) was evaluated.
      METHODS: Patients who underwent 23-G PPV for surgical removal of retained
      metallic IOFBs were retrospectively analyzed. OTS score for each patient was
      calculated and raw scores were converted to their corresponding OTS categories.
      The final VAs in study patients were compared with their respective OTS
      categories. RESULTS: Twenty-five eyes from 25 patients were examined. Twenty-four
      (96%) of the patients were male, and the mean age was 34 +/- 12 years. The time
      from injury to 23-G PPV was 9 +/- 4 days. Fourteen (56%) patients had zone 1
      trauma, eight (32%) patients had zone 2 trauma, and three (12%) patients had zone
      3 trauma. Postoperative visual acuity was >= 20/200 in 14 (56%) of the patients
      and >= 20/40 in seven (28%) eyes. At the final visit, anatomical success was
      achieved in 86% of patients with retinal detachment at presentation. No
      statistically significant differences were found between our final VAs and OTS
      scores. CONCLUSION: OTS, which provides prognostic information after general
      ocular trauma, may also provide valuable prognostic information for patients who
      undergo 23-G PPV for the surgical removal of metallic posterior segment IOFBs.

PMID- 30092768
TI  - Promoting prompt help-seeking for symptoms - assessing the impact of a
      gynaecological cancer leaflet on presentations to primary care: a record-based
      randomised control trial.
AB  - BACKGROUND: Information leaflets have been shown to significantly improve
      awareness of the symptoms of gynaecological cancers and to reduce perceived
      barriers to seeking medical help. This record-based, parallel, randomised control
      trial study aimed to assess whether receipt of a leaflet would change the
      behaviour of women experiencing symptoms indicative of gynaecological cancers by
      prompting them to visit their general practitioner (GP). METHODS: 15,538 women
      aged 40 years or over registered with five general practices in Northamptonshire,
      UK were randomised to two groups using the SystmOne randomise facility. Those in
      the intervention group received an educational leaflet from their general
      practice explaining the symptoms of gynaecological cancers and advising
      symptomatic women to visit their GP. The control group were not contacted.
      Electronic records were interrogated to extract sociodemographic data and details
      of GP consultations for symptoms, tests, referrals and diagnoses relating to
      gynaecological cancers in the 4-month period following the mail-out of the
      leaflets. RESULTS: 7739 records were extracted from the intervention group and
      7799 from the control group. 231 (3.0%) of the women in the intervention group,
      and 207 (2.7%) of the controls, presented to their GP with a relevant symptom
      during the 4-month period following leaflet distribution. The slightly higher
      rate in the intervention group did not reach statistical significance at the 5%
      level (RR = 1.11; 95% CI 0.92-1.33; z = 1.08; p = 0.28). There was a
      significantly lower mean time to first presentation in the symptomatic
      intervention group (57.2 days, sd = 36.5) compared to the control group (65.2
      days, sd = 35.0) (t = - 2.415; p = 0.016). Survival analysis did not reveal a
      difference between the patterns of presentation in the two cohorts (Log Rank
      (Mantel-Cox) chi2 = 1.42; p = 0.23). CONCLUSION: There was no difference between
      intervention and control groups in the proportion of women presenting with
      symptoms identified in the leaflet in the four months following leaflet
      distribution, although the women who had been sent a leaflet presented earlier
      than those in the control group. A larger study is needed to test for a modest
      effect of leaflet distribution. TRIAL REGISTRATION: Listed on the ISRCTN registry
      with study ID ISRCTN61738692 on 23-8-2017 (retrospectively registered).

PMID- 30092769
TI  - Epidemiology and surveillance of human animal-bite injuries and rabies post
      exposure prophylaxis, in selected counties in Kenya, 2011-2016.
AB  - BACKGROUND: Human animal-bite injuries are a serious public health problem due to
      associated risk for rabies virus exposure. Animal-bite injuries especially dog
      bites are useful indicators for assessing the risk of rabies virus transmission
      and need for rabies post exposure prophylaxis (PEP). Understanding the
      epidemiology and surveillance of animal bites and rabies post-exposure
      prophylaxis is critical in implementing Kenya's national rabies elimination
      strategy. We aimed to describe the incidence of human animal-bite injuries,
      patient/biting animal characteristics, uptake of rabies PEP and factors
      associated with animal bite incidents. METHODS: We reviewed animal bite records
      from outpatient and anti-rabies vaccine (ARV) registers of 17 health facilities
      from five counties. An animal bite was defined as an entry of an animal bite of
      the class mammal including humans in registers in a person of any age from
      January 2011 to December 2016. We collected demographic and information on PEP
      uptake. We calculated descriptive statistics, odds ratios (OR) and 95% confidence
      interval (CI) to examine factors associated with being an animal bite case
      patient. We also calculated incidence of animal bites using health facility
      catchment population for year 2016 as the denominator. RESULTS: We analyzed 7307
      records. The median age was 22 years (IQR = 31 years); there were 4019 (55%) male
      and age < 15 years were 2607 (37%). Dogs accounted for 6720 (93%) of bites of
      which 78% were owned free-roaming dogs. Of the 5674 (88%) cases that received
      rabies PEP, 2247 (40%) got at least three-doses. The median time from bite to
      seeking medical care was 2 days (IQR = 4 days). Being bitten on the head/face (OR
      = 5.8; CI: 3.3-10.2); being bitten by owned free-roaming dog (OR = 1.7; CI: 1.5
      1.9) and being male (OR = 1.4; CI: 1.3-1.5) were significantly associated with
      being an animal-bite case-patient. Being male, being bitten on head/face and
      being bitten by owned free-roaming dog remained independently associated with
      being an animal bite case-patient at multivariable logistic regression. Bite
      incidence was 289 bites /100,000 persons among all counties. CONCLUSION:
      Preventing dog bites would most effectively reduce bite injuries by improving
      public health education among children below 15 years, encouraging early PEP
      initiation and completion, development and implementation of responsible dog
      ownership and animal behaviour educational programmes as well as improving human
      and veterinary health linkages.

PMID- 30092770
TI  - Genomic diversity dynamics in conserved chicken populations are revealed by
      genome-wide SNPs.
AB  - BACKGROUND: Maintaining maximum genetic diversity and preserving breed viability
      in conserved populations necessitates the rigorous evaluation of conservation
      schemes. Three chicken breeds (Baier Yellow Chicken (BEC), Beijing You Chicken
      (BYC) and Langshan Chicken (LSC)) are currently in conservation programs in
      China. Changes in genetic diversity were measured by heterozygosity, genomic
      inbreeding coefficients, and autozygosity, using estimates derived from runs of
      homozygosity (ROH) that were identified using SNPs. RESULTS: Ninety DNA samples
      were collected from three generations for each breed. In the most recent
      generation, the highest genetic diversity was observed in LSC, followed by BEC
      and BYC. Inbreeding coefficients based on ROH for the three breeds declined
      slightly between the first and middle generations, and then rapidly increased. No
      inbreeding coefficients exceeded 0.1. Population structure assessments using
      neighbor-joining tree analysis, principal components analysis, and STRUCTURE
      analysis indicated that no genetic differentiation existed within breeds. LD
      decay and ROH at different cut-off lengths were used to identify traces left by
      recent or ancient inbreeding. Few long ROH were identified, indicating that
      inbreeding has been largely avoided with the current conservation strategy. The
      observed losses in genetic diversity and occurrences of inbreeding might be
      consequences of sub-optimal effective population sizes. CONCLUSIONS: The
      conserved Chinese chicken populations have high genomic diversity under the
      current conservation program (R: F). Furthermore, this study highlights the need
      to monitor dynamic changes in genetic diversity in conserved breeds over
      successive generations. Our research provides new insights into genetic diversity
      dynamics in conserved populations, and lays a solid foundation for improving
      conservation schemes.

PMID- 30092772
TI  - Early intervention program for very low birth weight preterm infants and their
      parents: a study protocol.
AB  - BACKGROUND: Preterm infants are high risk for delayed neurodevelopment. The main
      goal is to develop a program of early intervention for very preterm infants that
      allows families to apply it continuously at home, and quantify the results of
      early parental stimulation on improvement of cognition and motor skills. METHODS:
      Randomized clinical Trial including inborn preterm infants with gestational age
      less than 32 weeks or birth weight less than 1500 g at 48 h after birth. Eligible
      for begin the intervention up to 7 days after birth. Study Protocol approved by
      the Brazilian national Committee of ethics in Research and by the institutional
      ethics committee. Intervention group (IG): skin-to skin care by mother (kangaroo
      care) plus tactile-kinesthetic stimulation by mothers from randomization until
      hospital discharge when they receive a program of early intervention with 10
      parents' orientation and a total of 10 home visits independently of the standard
      evaluation and care that will be performed. Systematic early intervention program
      will be according to developmental milestones, anticipating in a month
      evolutionary step acquisition of motor and / or cognitive expected for corrected
      age. Active comparator with a Conventional Group (CG): standard care according to
      the routine care of the NICU and their needs in the follow up program.
      Neurodevelopment outcome with blinded evaluations in both groups between 12 and
      18 months by Bayley Scales of Infant and Toddler Development third edition and
      Alberta Motor Infant scale will be performed. All evaluations will be conducted
      in the presence of parents or caregivers in a safe room for the child move around
      during the evaluation. DISCUSSION: If we can show that a continuous and global
      early intervention at home performed by low income families is better than the
      standard care for very preterm infants, this kind of program may be applied
      elsewhere in the world. We received grants by Bill and Melinda Gates Foundation,
      DECIT, Cnpq and Health Ministry. Grand Challenges Brazil: All Children Thriving.
      TRIAL REGISTRATION: The study was restrospectively registered in
      ClinicalTrials.gov . in July 15 2016 ( NCT02835612 ).

PMID- 30092771
TI  - Low potassium and high sodium intakes: a double health threat to Cape Verdeans.
AB  - BACKGROUND: Cape Verde presents a high rate of cardiovascular diseases. Low
      potassium and high sodium intakes are related to cardiovascular diseases.
      However, studies regarding these two micronutrients continue to be rare in
      African urban settings. This work aims to estimate potassium and sodium intakes
      and to analyse the self-reported salt intake by gender and by type of urban area
      in the city of Praia - the capital of Cape Verde. METHODS: In the first stage (n
      = 1912), an intra-urban study was designed in two types of urban areas (formal
      and informal), using a sampling strategy based on random selection of
      geographical coordinates, in order to apply a questionnaire. In a second stage, a
      24-h dietary recall and anthropometric measurements were performed by local
      nutritionists. Potassium and sodium intakes were estimated for 599 participants
      (149 men and 450 women). Non-parametric methods (including quantile regression)
      were used in the statistical analysis. RESULTS: In informal areas, a higher
      percentage of women reported having hypertension (31.0%) compared to formal areas
      (19.7%). Based on 24-h dietary recall, median potassium intake for men was 2924.2
      mg/day and for women and 2562.6 mg/day. Almost 70.0% of men and 80.0% of women
      ingested less than the recommended 3510 mg/day of potassium. In informal areas,
      men and women presented high medians of sodium intakes compared to formal areas
      (men: 4131.2 vs 3014.6 mg/day and women: 3243.4 vs 2522.4 mg/day). On the other
      hand, the percentage of participants exceeding 2000 mg/day for sodium was high
      (>=70.8%), even for participants that self-reported low-salt intake. Quantile
      regression models revealed effects of the type of urban area and gender in the
      potassium and sodium intakes, at least, in some quartiles, accounting for age,
      academic qualifications, and professional situation. CONCLUSIONS: A low potassium
      intake and a high sodium intake were found in Praia. Thus, efficient health
      education campaigns and health promotion are needed and should be tailored
      considering gender and urban areas.

PMID- 30092773
TI  - The altered activity of P53 signaling pathway by STK11 gene mutations and its
      cancer phenotype in Peutz-Jeghers syndrome.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is caused by mutations in
      serine/threonine kinase 11 (STK11) gene. The increased cancer risk has been
      connected to P53 pathway. METHODS: PJS probands with STK11 mutation were included
      in the function analysis. P53 activity elevated by STK11 mutants was investigated
      using dual-luciferase reporter assay in vitro after constructing expression
      vectors of STK11 wild type and mutants generated by site-directed substitution.
      The association between the P53 activity and clinicopathological factors was
      analysis, especially the cancer history. RESULTS: Thirteen probands with STK11
      mutations were involved, and within the mutations, c.G924A was novel. P53
      activity elevation caused by 6 truncating mutations were significantly lower than
      that of STK11 wild type (P < 0.05). Family history of cancer was observed in 5
      families. Within them, P53 activity was reduced and cancer occurred before 40 in
      2 families, while it was not significantly changed and cancers happened after 45
      in the other 3 families. CONCLUSIONS: The affected P53 activity caused by STK11
      mutations in PJS patients is significantly associated with protein truncation,
      while cancer risk in PJS can be elevated through pathways rather than P53
      pathway. P53 activity test is probably a useful supporting method to predict
      cancer risk in PJS, which could be helpful in clinical practice.

PMID- 30092774
TI  - An early analysis of cost-utility of baroreflex activation therapy in advanced
      chronic heart failure in Germany.
AB  - BACKGROUND: This study aimed to evaluate cost-utility of baroreflex activation
      therapy (BAT) using the Barostim neoTM device (CVRx Inc., Minneapolis, MN, USA)
      compared with optimized medical management in patients with advanced chronic
      heart failure (NYHA class III) who were not eligible for treatment with cardiac
      resynchronization therapy, from a statutory health insurance perspective in
      Germany over a lifetime horizon. METHODS: A decision analytic model was developed
      using the combination of a decision tree and the Markov process. The model
      included transitions between New York Heart Association (NYHA) health states,
      each of which is associated with a risk of mortality, hospitalization, cost, and
      quality of life. The effectiveness of BAT was projected through relative risks
      for mortality (obtained by application of patient-level data to the Meta-analysis
      Global Group in Chronic Heart Failure risk prediction model) and hospitalization
      owing to worsening of heart failure (obtained from BAT Randomized Clinical
      Trial). All patients were in NYHA class III at baseline. RESULTS: BAT led to an
      incremental cost of ?33,185 (95% credible interval [CI] ?24,561-38,637) and
      incremental benefits of 1.78 [95% CI 0.45-2.71] life-years and 1.19 [95% CI 0.30
      1.81] quality-adjusted life-years (QALYs). This resulted in an incremental cost
      effectiveness ratio of ?27,951/QALY (95% CI ?21,357-82,970). BAT had a 59%
      probability of being cost-effective at a willingness-to-pay threshold of
      ?35,000/QALY (but 84% at a threshold of ?52,000/QALY). CONCLUSIONS: BAT can be
      cost-effective in European settings in those not eligible for cardiac
      resynchronization therapy among patients with advanced heart failure.

PMID- 30092776
TI  - Comparing SNP panels and statistical methods for estimating genomic breed
      composition of individual animals in ten cattle breeds.
AB  - BACKGROUND: SNPs are informative to estimate genomic breed composition (GBC) of
      individual animals, but selected SNPs for this purpose were not made available in
      the commercial bovine SNP chips prior to the present study. The primary objective
      of the present study was to select five common SNP panels for estimating GBC of
      individual animals initially involving 10 cattle breeds (two dairy breeds and
      eight beef breeds). The performance of the five common SNP panels was evaluated
      based on admixture model and linear regression model, respectively. Finally, the
      downstream implication of GBC on genomic prediction accuracies was investigated
      and discussed in a Santa Gertrudis cattle population. RESULTS: There were 15,708
      common SNPs across five currently-available commercial bovine SNP chips. From
      this set, four subsets (1,000, 3,000, 5,000, and 10,000 SNPs) were selected by
      maximizing average Euclidean distance (AED) of SNP allelic frequencies among the
      ten cattle breeds. For 198 animals presented as Akaushi, estimated GBC of the
      Akaushi breed (GBCA) based on the admixture model agreed very well among the five
      SNP panels, identifying 166 animals with GBCA = 1. Using the same SNP panels, the
      linear regression approach reported fewer animals with GBCA = 1. Nevertheless,
      estimated GBCA using both models were highly correlated (r = 0.953 to 0.992). In
      the genomic prediction of a Santa Gertrudis population (and crosses), the results
      showed that the predictability of molecular breeding values using SNP effects
      obtained from 1,225 animals with no less than 0.90 GBC of Santa Gertrudis (GBCSG)
      decreased on crossbred animals with lower GBCSG. CONCLUSIONS: Of the two
      statistical models used to compute GBC, the admixture model gave more consistent
      results among the five selected SNP panels than the linear regression model. The
      availability of these common SNP panels facilitates identification and estimation
      of breed compositions using currently-available bovine SNP chips. In view of
      utility, the 1 K panel is the most cost effective and it is convenient to be
      included as add-on content in future development of bovine SNP chips, whereas the
      10 K and 16 K SNP panels can be more resourceful if used independently for
      imputation to intermediate or high-density genotypes.

PMID- 30092775
TI  - Strategy for efficient generation of numerous full-length cDNA clones of
      classical swine fever virus for haplotyping.
AB  - BACKGROUND: Direct molecular cloning of full-length cDNAs derived from viral RNA
      is an approach to identify the individual viral genomes within a virus
      population. This enables characterization of distinct viral haplotypes present
      during infection. RESULTS: In this study, we recover individual genomes of
      classical swine fever virus (CSFV), present in a pig infected with vKos that was
      rescued from a cDNA clone corresponding to the highly virulent CSFV Koslov
      strain. Full-length cDNA amplicons (ca. 12.3 kb) were made by long RT-PCR, using
      RNA extracted from serum, and inserted directly into a cloning vector prior to
      detailed characterization of the individual viral genome sequences. The amplicons
      used for cloning were deep sequenced, which revealed low level sequence variation
      (< 5%) scattered across the genome consistent with the clone-derived origin of
      vKos. Numerous full-length cDNA clones were generated using these amplicons and
      full-genome sequencing of individual cDNA clones revealed insights into the virus
      diversity and the haplotypes present during infection. Most cDNA clones were
      unique, containing several single-nucleotide polymorphisms, and phylogenetic
      reconstruction revealed a low degree of order. CONCLUSIONS: This optimized
      methodology enables highly efficient construction of full-length cDNA clones
      corresponding to individual viral genomes present within RNA virus populations.

PMID- 30092778
TI  - International pilot external quality assessment scheme for analysis and reporting
      of circulating tumour DNA.
AB  - BACKGROUND: Molecular analysis of circulating tumour DNA (ctDNA) is becoming
      increasingly important in clinical treatment decisions. A pilot External Quality
      Assessment (EQA) scheme for ctDNA analysis was organized by four European EQA
      providers under the umbrella organization IQN Path, in order to investigate the
      feasibility of delivering an EQA to assess the detection of clinically relevant
      variants in plasma circulating cell-free DNA (cfDNA) and to analyze reporting
      formats. METHODS: Thirty-two experienced laboratories received 5 samples for EGFR
      mutation analysis and/or 5 samples for KRAS and NRAS mutation analysis. Samples
      were artificially manufactured to contain 3 mL of human plasma with 20 ng/mL of
      fragmented ctDNA and variants at allelic frequencies of 1 and 5%. RESULTS: The
      scheme error rate was 20.1%. Higher error rates were observed for RAS testing
      when compared to EGFR analysis, for allelic frequencies of 1% compared to 5%, and
      for cases including 2 different variants. The reports over-interpreted wild-type
      results and frequently failed to comment on the amount of cfDNA extracted.
      CONCLUSIONS: The pilot scheme demonstrated the feasibility of delivering a ctDNA
      EQA scheme and the need for such a scheme due to high error rates in detecting
      low frequency clinically relevant variants. Recommendations to improve reporting
      of cfDNA are provided.

PMID- 30092777
TI  - Use of plasma mitochondrial DNA levels for determining disease severity and
      prognosis in pediatric sepsis: a case control study.
AB  - BACKGROUND: The mortality rate due to severe sepsis is approximately 30-60%.
      Sepsis readily progresses to septic shock and multiple organ dysfunction,
      representing a significant problem in the pediatric intensive care unit (PICU).
      The aim of this study was to explore the value of plasma mitochondrial DNA
      (mtDNA) for early diagnosis and prognosis in children with sepsis. METHODS: A
      total of 123 children with sepsis who were hospitalized in the Hunan Children's
      Hospital PICU from July 2013 to December 2014 were divided into the general
      sepsis group (n = 70) and severe sepsis group (n = 53) based on diagnostic
      standards. An additional 30 children with non-sepsis infection and 30 healthy
      children were randomly selected as a control group. Patients' plasma was
      collected during admission to the PICU. A pediatric critical illness score (PCIS)
      was also calculated. The plasma mtDNA level was examined using real-time
      polymerase chain reaction technology, and other parameters including routine
      laboratory values; blood lactate, procalcitonin (PCT), and C-reactive protein
      (CRP) levels; and data on survival were collected and compared among the groups.
      RESULTS: The plasma mtDNA level in the sepsis group than that in the non-sepsis
      infection and healthy groups. The plasma mtDNA level was significantly higher in
      the severe sepsis than in the general sepsis group (p < 0.001). A lower PCIS was
      associated with a higher plasma mtDNA level (p < 0.001). A higher number of
      organs with dysfunction was associated with higher plasma mtDNA levels (p <
      0.001). Plasma mtDNA levels were higher among patients with elevated alanine
      aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine,
      lactate dehydrogenase, creatine kinase, myoglobin, creatine kinase MB, and
      troponin than in those with values within the normal range. The mtDNA level was
      higher among non-survivors than among survivors, and this difference was
      significant. mtDNA showed a prognostic prediction value similar to that of
      lactate, PCT, and CRP. CONCLUSIONS: Plasma mtDNA levels may be a suitable
      biomarker for diagnosis and prognosis in children with sepsis.

PMID- 30092780
TI  - Impact of matrix-assisted laser desorption/ionization time of flight mass
      spectrometric evaluation on the clinical outcomes of patients with bacteremia and
      fungemia in clinical settings lacking an antimicrobial stewardship program: a pre
      post quasi experimental study.
AB  - BACKGROUNDS: Several studies have evaluated the impact of matrix-assisted laser
      desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) combined
      with antimicrobial stewardship in patients with positive blood cultures; clinical
      outcomes improved. However, in many hospitals, antimicrobial stewardship is not
      available because of restricted medical resources. Thus, we investigated the
      impact of evaluation by MALDI-TOF MS on the clinical outcomes of patients with
      bacteremia and fungemia treated in a clinical setting lacking an antimicrobial
      stewardship program (ASP). METHODS: We designed a pre-post quasi experimental
      study and retrospectively reviewed the medical records of patients aged > 18
      years old with bacteremia and fungemia during two periods: October-December 2012
      and October-December 2013. Conventional methods were used to detect microbial
      pathogens in 2012, and MALDI-TOF MS was employed in 2013. Clinical outcomes
      compared between periods were the time to pathogen identification, time to
      effective therapy, 30-day all-cause mortality, time to microbiological clearance,
      length of ICU stay, and rate of recurrence of the same bloodstream infection
      (BSI). RESULTS: A total of 556 patients were enrolled; 302 patients in 2012, and
      254 in 2013. The use of MALDI-TOF MS without an ASP reduced the time to pathogen
      identification (86.4 vs. 63.5 h, P < 0.001) but did not significantly reduce the
      time to effective therapy (27.4 vs. 23.2 h, P = 0.187). Also, none of the
      following differed significantly between the two periods: mortality (17.5 vs.
      15.7%, P = 0.571), the time to microbiological clearance (3.6 vs. 3.7 days, P =
      0.675), the length of ICU stay (16.8 vs. 14.7 days, P = 0.706), and the
      recurrence rate of the same BSI (5.0 vs. 2.8%, P = 0.183). CONCLUSIONS: The use
      of MALDI-TOF MS alone in a setting lacking an ASP did not afford clinical
      benefits. An ASP combined with MALDI-TOF MS is necessary to improve clinical
      outcomes.

PMID- 30092779
TI  - Genome-wide identification of lipoxygenase gene family in cotton and functional
      characterization in response to abiotic stresses.
AB  - BACKGROUND: Plant lipoxygenase (LOX) genes are members of the non-haeme iron
      containing dioxygenase family that catalyze the oxidation of polyunsaturated
      fatty acids into functionally diverse oxylipins. The LOX family genes have been
      extensively studied under biotic and abiotic stresses, both in model and non
      model plant species; however, information on their roles in cotton is still
      limited. RESULTS: A total of 64 putative LOX genes were identified in four cotton
      species (Gossypium (G. hirsutum, G. barbadense, G. arboreum, and G. raimondii)).
      In the phylogenetic tree, these genes were clustered into three categories (9
      LOX, 13-LOX type I, and 13-LOX type II). Segmental duplication of putative LOX
      genes was observed between homologues from A2 to At and D5 to Dt hinting at
      allopolyploidy in cultivated tetraploid species (G. hirsutum and G. barbadense).
      The structure and motif composition of GhLOX genes appears to be relatively
      conserved among the subfamilies. Moreover, many cis-acting elements related to
      growth, stresses, and phytohormone signaling were found in the promoter regions
      of GhLOX genes. Gene expression analysis revealed that all GhLOX genes were
      induced in at least two tissues and the majority of GhLOX genes were up-regulated
      in response to heat and salinity stress. Specific expressions of some genes in
      response to exogenous phytohormones suggest their potential roles in regulating
      growth and stress responses. In addition, functional characterization of two
      candidate genes (GhLOX12 and GhLOX13) using virus induced gene silencing (VIGS)
      approach revealed their increased sensitivity to salinity stress in target gene
      silenced cotton. Compared with controls, target gene-silenced plants showed
      significantly higher chlorophyll degradation, higher H2O2, malondialdehyde (MDA)
      and proline accumulation but significantly reduced superoxide dismutase (SOD)
      activity, suggesting their reduced ability to effectively degrade accumulated
      reactive oxygen species (ROS). CONCLUSION: This genome-wide study provides a
      systematic analysis of the cotton LOX gene family using bioinformatics tools.
      Differential expression patterns of cotton LOX genes in different tissues and
      under various abiotic stress conditions provide insights towards understanding
      the potential functions of candidate genes. Beyond the findings reported here,
      our study provides a basis for further uncovering the biological roles of LOX
      genes in cotton development and adaptation to stress conditions.

PMID- 30092781
TI  - Comparison of local tumor control in patients with HCC treated with SBRT or TACE:
      a propensity score analysis.
AB  - BACKGROUND: As stereotactic body radiation therapy (SBRT) has shown to be
      effective and safe in patients with hepatocellular carcinoma (HCC), the aim of
      our propensity score matched analysis was to evaluate the efficacy of SBRT in
      comparison to transarterial chemoembolization (TACE) in intermediate and advanced
      HCC. METHODS: Patients treated with TACE (n = 367) and patients allocated to SBRT
      (n = 35) were enrolled in this study. Propensity score matching was performed to
      adjust for differences in baseline and tumor characteristics of TACE and SBRT
      patients. Local tumor control (LC) 1 year after treatment, overall survival (OS)
      and 1-year mortality were assessed. RESULTS: Patients treated with SBRT have
      received more prior HCC treatments compared to TACE patients. The LC 1 year after
      treatment in the unmatched cohort was 74.4% for TACE patients compared to 84.8%
      in the SBRT group. Patients treated with TACE showed significantly improved OS
      (17.0 months vs. 9.0 months, p = 0.016). After propensity score matching, the LC
      in the TACE (n = 70) and SBRT (n = 35) group was comparable (82.9% vs. 84.8%, p =
      0.805) and OS did not differ significantly in both groups. CONCLUSIONS: SBRT
      after prior HCC therapy in selected patients shows comparable LC at 1 year, OS
      and 1-year mortality compared to patients treated with TACE.

PMID- 30092782
TI  - Sodium and potassium excretion in an adult Caribbean population of African
      descent with a high burden of cardiovascular disease.
AB  - BACKGROUND: High sodium diets with inadequate potassium and high sodium-to
      potassium ratios are a known determinant of hypertension and cardiovascular
      disease (CVD). The Caribbean island of Barbados has a high prevalence of
      hypertension and mortality from CVD. Our objectives were to estimate sodium and
      potassium excretion, to compare estimated levels with recommended intakes and to
      identify the main food sources of sodium in Barbadian adults. METHODS: A sub
      sample (n = 364; 25-64 years) was randomly selected from the representative
      population-based Health of the Nation cross-sectional study (n = 1234), in 2012
      13. A single 24-h urine sample was collected from each participant, following a
      strictly applied protocol designed to reject incomplete samples, for the
      measurement of sodium and potassium excretion (in mg), which were used as proxy
      estimates of dietary intake. In addition, sensitivity analyses based on estimated
      completeness of urine collection from urine creatinine values were undertaken.
      Multiple linear regression was used to examine differences in sodium and
      potassium excretion, and the sodium-to-potassium ratio, by age, sex and
      educational level. Two 24-h recalls were used to identify the main dietary
      sources of sodium. All analyses were weighted for the survey design. RESULTS:
      Mean sodium excretion was 2656 (2488-2824) mg/day, with 67% (62-73%) exceeding
      the World Health Organization (WHO) recommended limit of 2000 mg/d. Mean
      potassium excretion was 1469 (1395-1542) mg/d; < 0.5% met recommended minimum
      intake levels. Mean sodium-to-potassium ratio was 2.0 (1.9-2.1); not one
      participant had a ratio that met WHO recommendations. Higher potassium intake and
      lower sodium-to-potassium ratio were independently associated with age and
      tertiary education. Sensitivity analyses based on urine creatinine values did not
      notably alter these findings. CONCLUSIONS: In this first nationally
      representative study with objective assessment of sodium and potassium excretion
      in a Caribbean population in over 20 years, levels of sodium intake were high,
      and potassium intake was low. Younger age and lower educational level were
      associated with the highest sodium-to-potassium ratios. These findings provide
      baseline values for planning future policy interventions for non-communicable
      disease prevention.

PMID- 30092784
TI  - The role of environmental health in the Basotho male initiation schools:
      neglected or restricted?
AB  - The aim of this paper is to point the Environmental Health (EH) profession in
      South Africa in the direction of their neglected function. The health inspection
      of initiation schools is one of the abandoned responsibility of EH profession in
      South Africa. This is due to fear of interfering with the traditional value
      systems and thus resulting in significant non-compliance to EH norms and
      standards. Little information is available on the compliance rate of EH
      requirements in the African traditional initiation schools. South African
      National Department of Health states that EHPs have an obligation to protect the
      health, safety and well-being of citizens from the environmental determinants,
      and this is achieved through enforcing the health requirements. In terms of the
      norms and standards for EH, health education in initiation schools should form an
      integral part of monitoring and evaluation, and this is found under the health
      surveillance of premises. The main argument raised by this paper is negligence of
      EHPs to conduct EH inspections at the Basotho male initiation schools and to
      promote health in support of the constitution of South Africa. Negligence of EHPs
      to perform their duties result in deaths and fatal injuries among initiates and
      this indicates the need for health promotion and EH research in the Basotho male
      initiation schools.

PMID- 30092785
TI  - Intimate partner violence against women in Nigeria: a multilevel study
      investigating the effect of women's status and community norms.
AB  - BACKGROUND: Intimate partner violence (IPV) against women has been recognised as
      a public health problem with far-reaching consequences for the physical,
      reproductive, and mental health of women. The ecological framework portrays
      intimate partner violence as a multifaceted phenomenon, demonstrating the
      interplay of factors at different levels: individual, community, and the larger
      society. The present study examined the effect of individual- and community-level
      factors on IPV in Nigeria, with a focus on women's status and community-level
      norms among men. METHODS: A cross-sectional study based on the latest Nigerian
      Demographic Health Survey (2013) was conducted involving 20,802 ever-partnered
      women aged 15-49 years. Several multilevel logistic regression models were
      calibrated to assess the association of individual- and community-level factors
      with IPV. Both measures of association (fixed effect) and measures of variations
      (random effect) were reported. RESULTS: Almost one in four women in Nigeria
      reported having ever experienced intimate partner violence. Having adjusted for
      other relevant covariates, higher women's status reduced the odds of IPV (OR =
      0.47; 95% CI = 0.32-0.71). However, community norms among men that justified IPV
      against women modified the observed protective effect of higher women's status
      against IPV and reversed the odds (OR = 1.89; 95% CI = 1.26-2.83). CONCLUSIONS:
      Besides women's status, community norms towards IPV are an important factor for
      the occurrence of IPV. Thus, addressing intimate partner violence against women
      calls for community-wide approaches aimed at changing norms among men alongside
      improving women's status.

PMID- 30092783
TI  - Outcomes of community-based and home-based pulmonary rehabilitation for
      pneumoconiosis patients: a retrospective study.
AB  - BACKGROUND: Pneumoconiosis patients receive community-based or home-based
      pulmonary rehabilitation (PR) for symptom management and enhancement of physical
      and mental well-being. This study aimed to review the clinical benefits of
      community-based rehabilitation programmes (CBRP) and home-based rehabilitation
      programmes (HBRP) for PR of pneumoconiosis patients. METHODS: Archival data of
      pneumoconiosis patients who participated in CBRP and HBRP between 2008 and 2011
      was analysed. There were 155 and 26 patients in the CBRP and HBRP respectively.
      The outcome measures used in the pre- and post-tests were Knowledge, Health
      Survey Short Form-12 (SF-12), Hospital Anxiety and Depression Scale (HADS), 6-Min
      Walk Test (6MWT), and Chronic Respiratory Questionnaire (CRQ). Paired t-tests and
      the Analysis of Covariance (ANCOVA) using the patients' baseline lung functions
      as the covariates were performed to examine the changes in the outcomes after
      completing the programmes. Hierarchical multiple regression analyses were used to
      examine the relationships between patient's programme participation factors and
      different scores of the outcome measures. RESULTS: After controlling for
      patients' baseline lung capacities, significant improvements were revealed among
      patients participated in CBRP in the scores of the 6MWT, Knowledge, HADS, SF-12
      PCS, and CRQ emotion and mastery. The different scores in the Knowledge and HADS
      were correlated with the patients' levels of programme participation. In
      contrast, significant improvements were only found in the scores of the Knowledge
      and 6MWT among patients who participated in HBRP. The gain scores of the 6MWT
      were correlated with the patients' levels of programme participation.
      CONCLUSIONS: Both CBRP and HBRP benefited patients' levels of exercise tolerance
      and knowledge about the disease. CBRP provided greater benefits to patients'
      mental and psychosocial needs. In contrast, HBRP was found to improve patients'
      physical function, but did not have significant impacts on patients' mental
      health and health-related quality of life. The attendance of patients and the
      participation of their relatives in treatment sessions were important factors in
      enhancing the positive effects of CBRP and HBRP. These positive outcomes confirm
      the value of pulmonary rehabilitation programmes for community-dwelling
      pneumoconiosis patients.

PMID- 30092786
TI  - Clinical analysis of treatment strategies to cholecystocholedocholithiasis
      patients with previous subtotal or total gastrectomy: a retrospective cohort
      study.
AB  - BACKGROUND: Previous gastrectomy can lead to an increased incidence of
      cholecystocholedocholithiasis (CCL) and increased morbidity rate. However, the
      appropriate treatment strategy for patients with CCL and a history of gastrectomy
      remains unclear. METHODS: We performed a retrospective cohort study of patients
      with CCL and a history of gastrectomy who underwent either one-stage laparoscopic
      common bile duct (CBD) exploration with stone clearance and laparoscopic
      cholecystectomy (LCBDE+LC) or two-stage endoscopic retrograde
      cholangiopancreatography followed by LC (ERCP+LC) from May 2010 to March 2018.
      RESULTS: The success rate of ERCP for CBD stone clearance was 81.2% in patients
      with a history of Billroth I gastrectomy and 23.7% in patients with a history of
      Billroth II or Roux-en-Y esophagojejunostomy [chi2 = 97.67, P < 0.001, risk ratio
      (RR) = 3.43]. The success rate of second-step LC after successful ERCP for
      removal of CBD stones and the success rate of LCBDE+LC after ERCP treatment
      failure were 96.8 and 87.7%, respectively, in patients with preoperative intra
      abdominal adhesion evaluation scores of <=3 points. These success rates were 28.6
      and 27.6%, respectively, in patients with scores of > 3 points (chi2 = 59.70, P <
      0.001, RR = 3.38 and chi2 = 53.41, P < 0.001, RR = 3.27, respectively).
      CONCLUSIONS: Based on the results of this study, ERCP+LC seems to be an
      attractive strategy for treatment of CCL in patients with a history of Billroth I
      gastrectomy, and LCBDE+LC appears to be suitable for patients with a history of
      Billroth II or Roux-en-Y esophagojejunostomy. Preoperative evaluation of intra
      abdominal adhesions helps to reduce the conversion rate of laparoscopic surgery.

PMID- 30092787
TI  - Morning blood pressure surge and its relation to insulin resistance in patients
      of reproductive age with polycystic ovary syndrome.
AB  - BACKGROUND: Our aim in this study was to investigate morning blood pressure surge
      (MBPS) in patients of reproductive age with polycystic ovary syndrome (PCOS) and
      its relation to insulin resistance (IR). METHODS: Fifty-three patients with PCOS
      without additional illness were included in the study. Forty-two age-matched
      subjects without PCOS were selected as the control group. All study subjects
      underwent 24-h blood pressure monitoring. Patients with additional illnesses,
      drug users, smokers, and alcohol and drug abusers were excluded. Blood insulin,
      fasting glucose, lipid profile, and hormone profile were measured. Insulin
      resistance was calculated using the HOMA-IR formula. RESULTS: Median age (years)
      was 27 (20-33) in the PCOS group and 27 (22-33) in the control group. Body mass
      index was higher in the PCOS group. Office systolic and diastolic blood pressure
      was higher in the PCOS group. Mean awakening 2-h BPs (mmHg) was 110 +/- 7 in the
      control group and 118 +/- 5 in the PCOS group (p < 0.001). Mean MBPS (mmHg) was
      21 +/- 6 in the control group and 29 +/- 8 in the PCOS group. Mean MBPS was
      higher in the PCOS group (p < 0.001). IR was more frequent in the PCOS group.
      Based on logistic regression analysis, the presence of PCOS and IR were
      independent predictors for MBPS. CONCLUSIONS: The results of our study showed
      that MBPS increased excessively when compared to non-PCOS controls in young women
      with PCOS during reproductive age. In addition, PCOS and insulin resistance were
      independent risk factors for exaggerated MBPS.

PMID- 30092788
TI  - Health-related quality of life in children with PFAPA syndrome.
AB  - BACKGROUND: Conventionally, PFAPA syndrome is considered as a benign disease
      compared to other recurrent fevers because it completely passes before adulthood.
      However, in our clinical practice, fever episodes have a huge impact on daily
      activities. METHODS: Observational cohort study using the Pediatric Quality of
      Life Inventory (PedsQLTM 4.0) Generic Core and Fatigue Scales. PedsQLTM uses a
      modular approach to measure the HRQOL in children with acute and chronic health
      conditions. We used pediatric FMF patients as the control group. RESULTS: We
      included 33 children with PFAPA and compared them to 27 FMF patients matched for
      age: preschool-age children (2 to 7 years) and school-age children and youths (8
      to18 years). PedsQLTM self-reported scores of children with PFAPA were
      systematically lower than those of FMF peers for general quality of life and
      physical and psychosocial functioning (significant only in the preschool-age
      group). PedsQLTM self-reported fatigue scores of children with PFAPA were
      significantly lower than those of FMF peers for both preschoolers and school-age
      children and youths. Parent proxy-reports were not significantly different, even
      though scores were systematically lower for the parents of PFAPA children.
      CONCLUSION: Our study demonstrates, for the first time, that the wellbeing of
      PFAPA children is poor, with a major impact on psychosocial functioning and
      increased fatigue. The quality of life of PFAPA children appears to be even lower
      than that of FMF patients, for whom a lower than normal HRQOL has already been
      demonstrated.

PMID- 30092789
TI  - TSSC3 promotes autophagy via inactivating the Src-mediated PI3K/Akt/mTOR pathway
      to suppress tumorigenesis and metastasis in osteosarcoma, and predicts a
      favorable prognosis.
AB  - BACKGROUND: Over the last two or three decades, the pace of development of
      treatments for osteosarcoma tends has been slow. Novel effective therapies for
      osteosarcoma are still lacking. Previously, we reported that tumor-suppressing
      STF cDNA 3 (TSSC3) functions as an imprinted tumor suppressor gene in
      osteosarcoma; however, the underlying mechanism by which TSSC3 suppresses the
      tumorigenesis and metastasis remain unclear. METHODS: We investigated the dynamic
      expression patterns of TSSC3 and autophagy-related proteins (autophagy related 5
      (ATG5) and P62) in 33 human benign bone tumors and 58 osteosarcoma tissues using
      immunohistochemistry. We further investigated the correlations between TSSC3 and
      autophagy in osteosarcoma using western blotting and transmission electronic
      microscopy. CCK-8, Edu, and clone formation assays; wound healing and Transwell
      assays; PCR; immunohistochemistry; immunofluorescence; and western blotting were
      used to investigated the responses in TSSC3-overexpressing osteosarcoma cell
      lines, and in xenografts and metastasis in vivo models, with or without autophagy
      deficiency caused by chloroquine or ATG5 silencing. RESULTS: We found that ATG5
      expression correlated positively with TSSC3 expression in human osteosarcoma
      tissues. We demonstrated that TSSC3 was an independent prognostic marker for
      overall survival in osteosarcoma, and positive ATG5 expression associated with
      positive TSSC3 expression suggested a favorable prognosis for patients. Then, we
      showed that TSSC3 overexpression enhanced autophagy via inactivating the Src
      mediated PI3K/Akt/mTOR pathway in osteosarcoma. Further results suggested
      autophagy contributed to TSSC3-induced suppression of tumorigenesis and
      metastasis in osteosarcoma in vitro and in vivo models. CONCLUSIONS: Our findings
      highlighted, for the first time, the importance of autophagy as an underlying
      mechanism in TSSC3-induced antitumor effects in osteosarcoma. We also revealed
      that TSSC3-associated positive ATG5 expression might be a potential predictor of
      favorable prognosis in patients with osteosarcoma.

PMID- 30092790
TI  - Clinical experiences with a PEEK-based dynamic instrumentation device in lumbar
      spinal surgery: 2 years and no more.
AB  - BACKGROUND: Dynamic spine implants were developed to prevent adjacent segment
      degeneration (ASD) and adjacent segment disease (ASDi). Purpose of this study was
      to investigate the clinical and radiological outcomes of "topping off" devices
      following lumbar spinal fusion procedure using a PEEK-based dynamic rod system.
      Moreover, this study focused on the hypothesis that "topping off" devices can
      prevent ASD. METHODS: This prospective nonrandomized study included patients with
      indication for single-level lumbar fusion and radiological signs of ASD without
      instability. The exclusion criteria were previous lumbar spine surgery and no
      sign of disc degeneration in the adjacent segment according to magnetic resonance
      imaging. All patients were treated with single-level lumbar interbody fusion and
      dynamic stabilization of the cranial adjacent segment. Patients underwent a
      clinical examination and radiographs preoperatively and at 1 and 2 years after
      surgery. Analyses were performed on clinical data collected with the German Spine
      Registry using the core outcome measure index (COMI) and visual analogue scale
      (VAS) scores for back and leg pain. RESULTS: A total of 22 patients (6 male and
      16 female) with an average age of 57.6 years were included in the study; 20
      patients completed the follow-up (FU). The average COMI score was 9.0
      preoperatively, 4.2 at the 1-year FU, and 4.7 at the 2-year FU. The average
      preoperative VAS scores for back and leg pain were 7.7 and 7.1, respectively. At
      the 1-year FU, the scores were 4.25 for back pain and 2.2 for leg pain, and at
      the 2-year FU, the scores were 4.7 for back pain and 2.3 for leg pain. At FU,
      failure of the dynamic topping off implant material was verified in four cases,
      and ASD of the segment cranial to the topping off was confirmed in three cases.
      CONCLUSIONS: These results demonstrate significant improvements in clinical
      outcomes and pain reduction after lumbar spinal fusion with topping off at 2
      years after surgery. However, the implant failed due to the high rate of implant
      failure and the development of ASD in the segment cranial to the dynamic
      stabilized segment.

PMID- 30092791
TI  - Counteracting roles of MHCI and CD8+ T cells in the peripheral and central
      nervous system of ALS SOD1G93A mice.
AB  - BACKGROUND: The major histocompatibility complex I (MHCI) is a key molecule for
      the interaction of mononucleated cells with CD8+T lymphocytes. We previously
      showed that MHCI is upregulated in the spinal cord microglia and motor axons of
      transgenic SOD1G93A mice. METHODS: To assess the role of MHCI in the disease, we
      examined transgenic SOD1G93A mice crossbred with beta2 microglobulin-deficient
      mice, which express little if any MHCI on the cell surface and are defective for
      CD8+ T cells. RESULTS: The lack of MHCI and CD8+ T cells in the sciatic nerve
      affects the motor axon stability, anticipating the muscle atrophy and the disease
      onset. In contrast, MHCI depletion in resident microglia and the lack of CD8+ T
      cell infiltration in the spinal cord protect the cervical motor neurons delaying
      the paralysis of forelimbs and prolonging the survival of SOD1G93A mice.
      CONCLUSIONS: We provided straightforward evidence for a dual role of MHCI in the
      peripheral nervous system (PNS) compared to the CNS, pointing out regional and
      temporal differences in the clinical responses of ALS mice. These findings offer
      a possible explanation for the failure of systemic immunomodulatory treatments
      and suggest new potential strategies to prevent the progression of ALS.

PMID- 30092792
TI  - A circRNA-miRNA-mRNA network identification for exploring underlying pathogenesis
      and therapy strategy of hepatocellular carcinoma.
AB  - BACKGROUND: Circular RNAs (circRNAs) have received increasing attention in human
      tumor research. However, there are still a large number of unknown circRNAs that
      need to be deciphered. The aim of this study is to unearth novel circRNAs as well
      as their action mechanisms in hepatocellular carcinoma (HCC). METHODS: A
      combinative strategy of big data mining, reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR) and computational biology was employed to dig
      HCC-related circRNAs and to explore their potential action mechanisms. A
      connectivity map (CMap) analysis was conducted to identify potential therapeutic
      agents for HCC. RESULTS: Six differently expressed circRNAs were obtained from
      three Gene Expression Omnibus microarray datasets (GSE78520, GSE94508 and
      GSE97332) using the RobustRankAggreg method. Following the RT-qPCR corroboration,
      three circRNAs (hsa_circRNA_102166, hsa_circRNA_100291 and hsa_circRNA_104515)
      were selected for further analysis. miRNA response elements of the three circRNAs
      were predicted. Five circRNA-miRNA interactions including two circRNAs
      (hsa_circRNA_104515 and hsa_circRNA_100291) and five miRNAs (hsa-miR-1303, hsa
      miR-142-5p, hsa-miR-877-5p, hsa-miR-583 and hsa-miR-1276) were identified. Then,
      1424 target genes of the above five miRNAs and 3278 differently expressed genes
      (DEGs) on HCC were collected. By intersecting the miRNA target genes and the
      DEGs, we acquired 172 overlapped genes. A protein-protein interaction network
      based on the 172 genes was established, with seven hubgenes (JUN, MYCN, AR, ESR1,
      FOXO1, IGF1 and CD34) determined from the network. The Gene Oncology, Kyoto
      Encyclopedia of Genes and Genomes and Reactome enrichment analyses revealed that
      the seven hubgenes were linked with some cancer-related biological functions and
      pathways. Additionally, three bioactive chemicals (decitabine, BW-B70C and
      gefitinib) based on the seven hubgenes were identified as therapeutic options for
      HCC by the CMap analysis. CONCLUSIONS: Our study provides a novel insight into
      the pathogenesis and therapy of HCC from the circRNA-miRNA-mRNA network view.

PMID- 30092795
TI  - Somatosensory profiles of patients with chronic myogenic temporomandibular
      disorders in relation to their painDETECT score.
AB  - BACKGROUND: The purpose of this study was to characterize patients with chronic
      temporomandibular disorders (TMD) in terms of existing hyperalgesia against cold,
      heat and pressure. METHODS: The extent of hyperalgesia for pressure and thermal
      sensation in TMD patients was determined by the use of the painDETECT
      questionnaire ("Is cold or heat in this area occasionally painful?" "Does slight
      pressure in this area, e.g., with a finger, trigger pain?") and experimental
      somatosensory testing against thermal and pressure stimuli (Quantitative Sensory
      Testing; QST). In addition, we explored psychological comorbidity among the
      chronic TMD patients (hospital anxiety and depression scale, HADS-D and coping
      strategies questionnaire, CSQ). RESULTS: Nineteen patients with chronic TMD and
      38 healthy subjects participated in the study. N = 12 patients had a painDETECT
      score <= 12, n = 3 patients had a painDETECT score of 13-18 and n = 4 patients
      had a painDETECT score >= 19. TMD patients with painDETECT scores >=19 had
      moderately, strong or very strong enhancement of thermal and pressure pain
      perception, whereas patients with painDETECT scores 13-18 and <= 12 responded
      these questions with "never", "hardly noticed" or "slightly painful" (p < 0.05
      0.01). With increasing painDETECT scores we found increased hyperalgesia for
      pressure (p < 0.01) and thermal stimuli (p < 0.05) in QST. The patients with a
      painDETECT score >= 19 showed increased signs of anxiety (p < 0.05), depression
      (p < 0.01), praying and hoping (p < 0.05). CONCLUSION: The present study has
      shown that the PainDETECT questionnaire can be a helpful additional diagnostic
      tool. Together with QST, the PainDETECT questionnaire detected hyperalgesia for
      pressure and thermal sensation. Therefore the PainDETECT questionnaire is helpful
      to decide which TMD patients should undergo QST.

PMID- 30092794
TI  - The management strategies of cancer-associated anorexia: a critical appraisal of
      systematic reviews.
AB  - BACKGROUND: Cancer-related anorexia remains one of the most prevalent and
      troublesome clinical problems experienced by patients with cancer during and
      after therapy. To ensure high-quality care, systematic reviews (SRs) are seen as
      the best guide. Considering the methodology quality of SRs varies, we undertook a
      comprehensive overview, and critical appraisal of pertinent SRs. METHODS: Eight
      databases (between the inception of each database and September 1, 2017) were
      searched for SRs on the management of cancer-related anorexia. Two researchers
      evaluated the methodological quality of each SR by using the Revised Assessment
      of Multiple Systematic Reviews (R-AMSTAR) checklist. Characteristics of the "high
      quality" SRs were abstracted, included information on relevant studies numbers,
      study design, population, intervention, control, outcome and result. RESULTS:
      Eighteen SRs met the inclusion criteria. The R-AMSTAR scores of methodological
      quality ranged from 18 to 41 out of 44, with an average score of 30. Totally
      eight SRs scored >=31 points, which showed high methodological quality, and would
      be used for data extraction to make summaries. Anamorelin had some positive
      effects to relieve cancer anorexia-cachexia syndrome (CACS) and improve the
      quality of life (QoL). Megestrol Acetate (MA) could improve appetite, and was
      associated with slight weight gain for CACS. Oral nutritional interventions were
      effective in increasing nutritional intake and improving some aspects of QoL in
      patients with cancer who were malnourished or at nutritional risk. The use of
      thalidomide, Eicosapentaenoic Acid, and minerals, vitamins, proteins, or other
      supplements for the treatment of cachexia in cancer were uncertain, and there was
      inadequate evidence to recommend it to clinical practices, the same situation in
      Chinese Herb Medicine and acupuncture (acupuncture and related therapies were
      effective in improving QoL) for treating anorexia in cancer patients, warranting
      further RCTs in these areas. CONCLUSIONS: Anamorelin, MA, oral nutrition
      interventions, and acupuncture could be considered to be applied in patients with
      cancer-related anorexia. Future RCTs and SRs with high quality on the
      pharmaceutical or non-pharmaceutical interventions of anorexia in cancer patients
      are warranted.

PMID- 30092793
TI  - Predictors of postoperative hypocalcemia occurring after a total thyroidectomy:
      results of prospective multicenter study.
AB  - BACKGROUND: Thyroid surgeries are among the most common operations performed in
      the world. Hypocalcemia following total thyroidectomy is a common complication
      that is sometimes difficult to correct. The aim of this study is to determine the
      risk factors for hypocalcemia following total thyroidectomy and their clinical
      value. METHODS: From January 2015 through to April 2017, 400 patients were
      included in this prospective multicenter study. All patients underwent total
      thyroidectomy due to various thyroid diseases. The following risk factors were
      analyzed: pre-operative and post-operative biochemical blood parameters, clinical
      effects and factors related to surgery, the patient, and the disease. RESULTS:
      Post-operative hypocalcemia developed in 257 patients (64.2%). Of them, 197
      patients (76.7%) were diagnosed with asymptomatic hypocalcemia. Clinical symptoms
      were present in 60 of the 257 patients with hypocalcemia (23.3%). The
      statistically significant predictors of hypocalcemia were decreased calcium and
      ionized calcium pre-operatively (p < 0.001), parathyroid hormone on day one
      following surgery (p < 0.001), thyrotoxicosis <10 years before surgery (odds
      ratio 1.65, 95% CI 1.01-2.70, p = 0.046), the number of parathyroid glands found
      during surgery (odds ratio 0.52, 95% CI 0.38-0.70, p < 0.001), ligation of the
      trunk of the left inferior thyroid artery (odds ratio 2.04, 95% CI 1.27-3.29, p =
      0.003), ligation of the trunk of the right inferior thyroid artery (odds ratio
      2.37, 95% CI 1.47-3.81, p < 0.001), and the number of transplanted parathyroid
      glands (odds ratio 1.87, 95% CI 1.12-2.97, p = 0.015). In the multivariate
      analysis, age (odds ratio 1.05, 95% CI 1.01-1.09, p = 0.029) and gender (odds
      ratio 5.94, 95% CI 1.13-31.26, p = 0.035) were statistically significant
      predictors. CONCLUSIONS: This study demonstrates that there is a number of
      different patient (gender, age, and duration of thyrotoxicosis <10 years before
      surgery) and surgical (number of parathyroid glands found during surgery,
      decreased calcium and ionized calcium before surgery, parathyroid hormone on day
      one following surgery, and ligation of the trunk of the left and right inferior
      thyroid artery) risk factors predictive of hypocalcemia following total
      thyroidectomy. Optimization of the surgical technique could possibly prevent the
      occurrence of hypocalcemia after total thyroidectomy in some cases; in other
      cases, identification of known risk factors post-operatively could permit early
      detection and effective treatment of these patients.

PMID- 30092796
TI  - The effect of bitewing radiography on estimates of dental caries experience among
      children differs according to their disease experience.
AB  - BACKGROUND: Radiography is a regularly used and accepted adjunct to visual
      examination in the diagnosis of dental caries. It is assumed that not using
      radiographs can lead to underestimation of dental caries experience with most
      reports having involved studies of young adults or adolescents, and been focused
      on the permanent dentition. The aim of this study was to determine the relative
      contributions of bitewing radiography and clinical examination in the detection
      of dental caries in primary molars and to determine whether those contributions
      differ according to caries experience. METHODS: A cross-sectional study was
      conducted, involving examinations undertaken in dental clinics. Bitewing
      radiographs taken at the time of the clinical examination were developed and read
      later, with the data from those used at the analysis stage to adjust the caries
      diagnosis for the mesial, occlusal and distal surfaces of the primary molar
      teeth. Children's clinically determined dmfs score was used to allocate them to
      one of three caries experience groups (0 dmfs, 1-8 dmfs, or 9+ dmfs). RESULTS: Of
      the 501 three-to-eight-year-old children examined, nearly three-quarters were
      younger than six. Caries prevalence and mean dmfs after clinical examination
      alone and following radiographs were 63.1% and 4.6 (sd, 6.2), and 74.7% and 5.8
      (sd, 6.5) respectively. Among children with a dmfs of 1-8, the number of lesions
      missed during the clinical examination was greater than the number of 106 (25.6%)
      in children with a dmfs of 9+. In the 185 children with no apparent caries at
      clinical examination, 124 lesions were detected radiographically, among 58
      (46.8%) of those. CONCLUSIONS: Taking bitewing radiographs in young children is
      not without challenges or risks, and it must be undertaken with these in mind.
      Diagnostic yields from bitewing radiographs are greater for children with greater
      caries experience. The findings of this study further support the need to
      consider using bitewing radiographs in young children to enhance the management
      of lesions not detected by a simple visual examination alone. TRIAL REGISTRATION:
      ACTRN12614000844640 .

PMID- 30092797
TI  - Sotetsuflavone inhibits proliferation and induces apoptosis of A549 cells through
      ROS-mediated mitochondrial-dependent pathway.
AB  - BACKGROUND: Sotetsuflavone is isolated from Cycas revoluta Thunb., which has
      biological activity against tumors. However, the anti-proliferative effects of
      sotetsuflavone on A549 cells and its mechanism are not fully elucidated. METHODS:
      This study investigated the mechanisms of growth inhibition, cell cycle arrest
      and apoptosis in non-small cell lung cancer A549 cells induced by sotetsuflavone
      and evaluated whether sotetsuflavone can be safely utilized by humans as
      therapeutic agent. RESULTS: We found that sotetsuflavone had significant
      antiproliferative activity against A549 cells. At the same time, the reactive
      oxygen species (ROS) content increased while the mitochondrial membrane potential
      and the ratio of Bcl-2/Bax decreased. Cleaved caspase-3, cleaved caspase-9,
      cytochrome C and Bax expression increased, and Cyclin D1, CDK4, cleaved caspase-8
      and Bcl-2 expression decreased. Interestingly, we demonstrated that
      sotetsuflavone could effectively inhibit the G0/G1 cycle progression, and then
      induce the endogenous apoptosis pathway. Our results show that sotetsuflavone
      could inhibit the growth of A549 cells by up-regulating intracellular ROS levels
      and causing the mitochondrial membrane potential to collapse, inducing G0/G1
      phase arrest and endogenous apoptosis. CONCLUSIONS: In short, we confirm that
      sotetsuflavone had an inhibitory effect on A549 cells and discovered that it
      causes apoptosis of A549 lung cancer cells. Sotetsuflavone may be used as a novel
      candidate for anti-tumor therapy in patients with lung cancer.

PMID- 30092798
TI  - Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax
      circumsporozoite protein fail to produce salivary gland sporozoites.
AB  - BACKGROUND: Rodent malaria parasites where the gene encoding circumsporozoite
      protein (CSP) has been replaced with csp genes from the human malaria parasites,
      Plasmodium falciparum or Plasmodium vivax, are used as pre-clinical tools to
      evaluate CSP vaccines in vivo. These chimeric rodent parasites produce
      sporozoites in Anopheles stephensi mosquitoes that are capable of infecting
      rodent and human hepatocytes. The availability of chimeric P. falciparum
      parasites where the pfcsp gene has been replaced by the pvcsp would open up
      possibilities to test P. vivax CSP vaccines in small scale clinical trials using
      controlled human malaria infection studies. METHODS: Using CRISPR/Cas9 gene
      editing two chimeric P. falciparum parasites, were generated, where the pfcsp
      gene has been replaced by either one of the two major pvcsp alleles, VK210 or
      VK247. In addition, a P. falciparum parasite line that lacks CSP expression was
      also generated. These parasite lines have been analysed for sporozoite production
      in An. stephensi mosquitoes. RESULTS: The two chimeric Pf-PvCSP lines exhibit
      normal asexual and sexual blood stage development in vitro and produce sporozoite
      containing oocysts in An. stephensi mosquitoes. Expression of the corresponding
      PvCSP was confirmed in oocyst-derived Pf-PvCSP sporozoites. However, most oocysts
      degenerate before sporozoite formation and sporozoites were not found in either
      the mosquito haemocoel or salivary glands. Unlike the chimeric Pf-PvCSP
      parasites, oocysts of P. falciparum parasites lacking CSP expression do not
      produce sporozoites. CONCLUSIONS: Chimeric P. falciparum parasites expressing P.
      vivax circumsporozoite protein fail to produce salivary gland sporozoites.
      Combined, these studies show that while PvCSP can partially complement the
      function of PfCSP, species-specific features of CSP govern full sporozoite
      maturation and development in the two human malaria parasites.

PMID- 30092799
TI  - Feifukang ameliorates pulmonary fibrosis by inhibiting JAK-STAT signaling
      pathway.
AB  - BACKGROUND: Feifukang (FFK) is a traditional Chinese medicine composed of herbs
      that protect lung function. However, difficulty arises regarding the clinical
      application of FFK due to the complex mechanism of Chinese medicines. This study
      aimed to investigate the efficacy of FFK and explore its targeted genes and
      pathways. METHODS: Histopathological changes and collagen deposition were
      measured to evaluate the effect of FFK on bleomycin-induced pulmonary fibrosis in
      mice. The differentially expressed targeted genes and pathways were first
      screened using RNA sequencing. Then network pharmacology and other experiments
      were conducted to confirm RNA sequencing data. RESULTS: FFK treatment reduced the
      pathological score and collagen deposition, with a decrease in alpha-SMA and
      collagen. RNA sequencing and network pharmacology results all showed that FFK can
      ameliorate pulmonary fibrosis through multi-genes and multi-pathways. The
      targeted genes in JAK-STAT signaling pathway are some of the most notable
      components of these multi-genes and multi-pathways. Further experiments
      illustrated that FFK regulated phosphorylation of SMAD3, STAT3 and JAK1, and
      their co-expressed lncRNAs, which all are the important genes in JAK-STAT
      signaling pathway. CONCLUSION: FFK can ameliorate pulmonary fibrosis by
      inhibiting JAK-STAT signaling pathway and has potential therapeutic value for
      lung fibrosis treatment. Our study provides a new idea for the study of
      traditional Chinese medicine.

PMID- 30092800
TI  - Exoskeleton assistance symmetry matters: unilateral assistance reduces metabolic
      cost, but relatively less than bilateral assistance.
AB  - BACKGROUND: Many gait impairments are characterized by asymmetry and result in
      reduced mobility. Exoskeletons could be useful for restoring gait symmetry by
      assisting only one leg. However, we still have limited understanding of the
      effects of unilateral exoskeleton assistance. Our aim was to compare the effects
      of unilateral and bilateral assistance using a within-subject study design.
      METHODS: Eleven participants walked in different exoskeleton conditions. In the
      Unilateral conditions, only one leg was assisted. In Bilateral Matched Total
      Work, half of the assistance from the Unilateral conditions was applied to both
      legs such that the bilateral sum was equal to that of the Unilateral conditions.
      In Bilateral Matched Work Per Leg, the same assistance as in the Unilateral
      conditions was provided to both legs such that the bilateral sum was the double
      of that of the Unilateral conditions. In the Powered-Off condition, no assistance
      was provided. We measured metabolic energy consumption, exoskeleton mechanics and
      kinematics. RESULTS: On average, the Unilateral, Bilateral Matched Total Work and
      Bilateral Matched Work Per Leg conditions reduced the metabolic rate by 7, 11 and
      15%, respectively, compared with the Powered-Off condition. A possible
      explanation for why the Unilateral conditions effectively reduced the metabolic
      rate could be that they caused only very little asymmetry in gait biomechanics,
      except at the ankle and in the horizontal center-of-mass velocity. We found the
      highest ratio of metabolic rate reduction versus positive work assistance with
      bilateral assistance and low work per leg (Bilateral Matched Total Work).
      Statistical analysis indicated that assistance symmetry and assistance per leg
      are more important than the bilateral summed assistance for reducing the
      metabolic rate of walking. CONCLUSIONS: These data bridge the gap between
      conclusions from studies with unilateral and bilateral exoskeletons and inform
      how unilateral assistance can be used to influence gait parameters, such as
      center-of-mass velocity.

PMID- 30092801
TI  - Reducing hypnotic use in insomnia management among Australian veterans: results
      from repeated national interventions.
AB  - BACKGROUND: The Australian Government Department of Veterans' Affairs (DVA)
      Veterans' Medicines Advice and Therapeutics Education Services (Veterans' MATES)
      programme conducted two intervention (March 2009, follow-up intervention June
      2012) both of which aimed to reduce hypnotic use among Australian veterans. We
      evaluated the effectiveness of the interventions, and estimated the associated
      health consequences. METHODS: Both interventions targeted veterans who had been
      dispensed hypnotics prior to the intervention. Patient-specific prescriber
      feedback containing patient details and the volume of hypnotics dispensed, along
      with tailored educational information, was mailed to general practitioners.
      Veterans, pharmacists and directors of care in residential aged care facilities
      were mailed tailored educational information. Interrupted time-series and
      segmented regression modelling were used to determine the effect of the two
      interventions on the rate of hypnotics dispensing. The cumulative patient-months
      of hypnotic treatment avoided as a result of the interventions was calculated. We
      estimated improvements in health consequences of as a result of hypnotic
      treatment avoided based on the results of cohort studies in the same population
      identifying the association between hypnotic and sedative use on the outcomes of
      falls, and confusion. RESULTS: After the first Veterans' MATES intervention in
      March 2009, hypnotic use declined by 0.2% each month, when compared to the
      baseline level (p = 0.006). The intervention effect was attenuated after one
      year, and use of hypnotics was found to increase by 0.2% per month after March
      2010. Following the second intervention in June 2012, there was a further
      significant decline in use of 0.18% each month over the 12 months of follow up (p
      = 0.049). The cumulative effect of both interventions resulted in 20,850 fewer
      patient-months of treatment with hypnotics. This cumulative reduction in hypnotic
      use was estimated to lead to a minimum of 1 fewer hospital admissions for acute
      confusion and 7 fewer hospital admissions due to falls. CONCLUSIONS: The
      Veterans' MATES insomnia interventions which involved multiple stakeholders were
      effective in reducing hypnotic use among older Australians. Repetition of key
      messages led to sustained practice change.

PMID- 30092802
TI  - Picky eating in Swedish preschoolers of different weight status: application of
      two new screening cut-offs.
AB  - BACKGROUND: Characteristics of picky eaters of different weight status have not
      been sufficiently investigated. We used two newly developed screening cut-offs
      for picky eating in the Food fussiness (FF) subscale of the Child Eating Behavior
      Questionnaire (CEBQ) to investigate the prevalence and characteristics of picky
      eaters in preschool-aged children with thinness, normal weight, overweight or
      obesity. METHODS: Data for 1272 preschoolers (mean age 4.9 years) were analyzed.
      The parent-reported FF subscale ranges from 1 to 5, and two screening cut-offs
      were applied to classify children as picky eaters (3.0 and 3.33). Structural
      Equation Modeling was used to study associations with other factors in the CEBQ,
      the Child Feeding Questionnaire (CFQ) and the Lifestyle Behavior Checklist (LBC).
      Scores were compared separately for each weight status group. RESULTS: Nearly
      half of the children were classified as moderate or severe picky eaters (cut-off
      3.0) and 30% as severe (cut-off 3.33). For both cut-offs, prevalence was
      significantly lower in the obesity group. Still, one-third of children with
      obesity met the cut-off of 3.0 and 17% met the cut-off of 3.33. While picky
      eaters displayed similar patterns across weight status groups, some differences
      emerged. Food responsiveness was lower for picky eaters, but the difference was
      significant only among children with obesity. Slowness in eating was not as
      pronounced among picky eaters in the obesity group. In the overweight and obesity
      groups, parents of picky eaters did not report as high pressure to eat, as
      compared to the thinness or normal weight groups; in the obesity group, parents
      of picky eaters also perceived their children's weight as lower. In all weight
      status groups, parents of picky eaters were more likely to report their children
      had too much screen time, complained about physical activity, and expressed
      negative affect toward food. CONCLUSIONS: Picky eating was less common but still
      prevalent among children with obesity. Future studies should investigate the
      potential influence of picky eating on childhood overweight and obesity.
      Moreover, as children with picky eating display higher emotional sensitivity,
      further research is needed to understand how to create positive eating
      environments particularly for children with picky eating and obesity.

PMID- 30092803
TI  - Additional germline findings from a tumor profiling program.
AB  - BACKGROUND: Matched tumor-normal sequencing, applied in precision cancer
      medicine, can identify unidentified germline Medically Actionable Variants
      (gMAVS) in cancer predisposition genes. We report patient preferences for the
      return of additional germline results, and describe various gMAV scenarios
      delivered through a clinical genetics service. METHODS: Tumor profiling was
      offered to 1960 advanced cancer patients, of which 1556 underwent tumor-normal
      sequencing with multigene hotspot panels containing 20 cancer predisposition
      genes. All patients were provided with an IRB-approved consent for return of
      additional gMAVs. RESULTS: Of the whole cohort 94% of patients consented to be
      informed of additional germline results and 5% declined, with no statistically
      significant differences based on age, sex, race or prior genetic testing. Eight
      patients were found to have gMAVs in a cancer predisposition gene. Five had
      previously unidentified gMAVs: three in TP53 (only one fulfilled Chompret's
      Revised criteria for Li-Fraumeni Syndrome), one in SMARCB1 in the absence of
      schwannomatosis features and one a TP53 variant at low allele frequency
      suggesting an acquired event in blood. CONCLUSION: Interest in germline findings
      is high among patients who undergo tumor profiling. Disclosure of previously
      unidentified gMAVs present multiple challenges, thus supporting the involvement
      of a clinical genetics service in all tumor profiling programs.

PMID- 30092804
TI  - Craniofacial and oral alterations in patients with Neurofibromatosis 1.
AB  - ABTSRACT: Neurofibromatosis type 1 (NF1) is one of the most common inherited
      syndromes. The literature on craniofacial alterations associated with NF1 has
      been limited and partially contradictory. This review is based on literature
      search and the results of the clinical study "Craniofacial and Oral Alterations
      and Speech in patients with Neurofibromatosis 1", carried out at the University
      of Turku and Turku University Hospital, Finland in 2006-2012. By the end of 2012,
      a total of 110 NF1 patients, 54 female and 56 male patients, were examined.A part
      of our results confirms pre-existing understanding, a part is contradictory to
      previous considerations based mainly on case reports, and some are entirely
      novel. Specifically, our results confirmed that enlargement the mandibular canal
      is the most common abnormality of the mandible in patients with NF1. It should be
      noted, however, that this finding does not require treatment. Caries was not a
      major problem. In fact, it was less frequent in NF1 patients compared to
      reference population. These findings abrogate some previous perceptions. Novel
      findings of our project include periapical cemental dysplasia in females; short
      jaws, a finding which usually does not affect bite; and immunohistological
      analysis of oral mucosal abnormalities. Pioneering study on speech showed that
      various deviations were very common: As many as 94% of the participants showed
      some alterations.To conclude, the awareness of craniofacial alterations common in
      NF1would help avoiding unnecessary and even harmful involvement, e.g. of
      periapical cemental dysplasia or enlarged mandibular canal which do not require
      treatment.

PMID- 30092805
TI  - Investigating the existence of social networks in cheating behaviors in medical
      students.
AB  - BACKGROUND: Most studies on academic cheating rely on self-reported
      questionnaires and focus on the individual, overlooking cheating as a group
      activity. The aim of this study is to estimate the true prevalence of
      cheating/anomalies among medical students using a statistical index developed for
      this purpose, and to explore the existence of social networks between anomalies
      in students' results. METHODS: Angoff's A index was applied to a sample of 30
      written examinations, with a total of 1487 students and 7403 examinations taken,
      from the 2014/2015 academic year of the Faculty of Medicine of the University of
      Porto to detect anomaly pairs. All analyses are within the same academic year and
      not across years. Through simulations, the sensitivity and specificity of the
      statistical method was determined, and the true prevalence of anomalies/cheating
      was estimated. Networks of anomaly pairs were created to search for patterns and
      to calculate their density. RESULTS: The percentage of students who cheated at
      least once increased with the year of medical school, being lowest in the first
      year (3.4%) and highest in the fifth (17.3%). The year of medical school was
      associated with anomalies (p < 0.05). The network's density was also lowest in
      the first year (1.12E-04) and highest in the fifth (8.20E-04). The true
      prevalence of anomalies was estimated to be 1.85% (95%CI: 1.07-3.20%).
      CONCLUSIONS: These findings suggest that some students are involved in social
      networks of cheating, which grow over time, resulting in an increase of
      anomalies/cheating in later academic years.

PMID- 30092806
TI  - Change and variability in drug treatment coverage among people who inject drugs
      in 90 large metropolitan areas in the USA, 1993-2007.
AB  - BACKGROUND: Our previous research has found low and stable mean drug treatment
      coverage among people who inject drugs (PWID) across 90 large US metropolitan
      statistical areas (MSAs) during 1993-2002. This manuscript updates previous
      estimates of change in drug treatment coverage for PWID in 90 MSAs during 1993
      2007. METHODS: Our drug treatment sample for calculating treatment coverage
      includes clients enrolled in residential or ambulatory inpatient/outpatient care,
      detoxification services, and methadone maintenance therapy at publicly- and
      privately-funded substance abuse agencies receiving public funds. Coverage was
      measured as the number of PWID in drug treatment, calculated by using data from
      the Substance Abuse and Mental Health Service Administration, divided by numbers
      of PWID in each MSA. We modeled change in drug treatment coverage rates using a
      negative binomial mixed-effects model. Fixed-effects included an intercept and a
      main effect for time. Incidence rate ratios (IRR) were calculated for both
      average change from 1993 to 2007 and MSA-specific estimates of change in coverage
      rates. RESULTS: On average over all MSAs, coverage was low in 1993 (6.1%) and
      showed no improvement from 1993 to 2007 (IRR = 0.99; 95% CI, 0.86, 1.2). There
      was modest variability across MSAs in coverage in 1993 (log incidence rate SD =
      0.36) as well as in coverage change from 1993 to 2007 (log IRR SD = 0.32). In
      addition, results indicate significant variability among MSAs in coverage.
      CONCLUSIONS: Inadequate treatment coverage for PWID may produce a high cost to
      society in terms of the spread of overdose mortality and injection-related
      infectious diseases. A greater investment in treatment will likely be needed to
      have a substantial and more consistent impact on injection drug use-related
      harms. Future research should examine MSA-level predictors associated with
      variability in drug treatment coverage.

PMID- 30092807
TI  - Calcar screws and adequate reduction reduced the risk of fixation failure in
      proximal humeral fractures treated with a locking plate: 190 patients followed
      for a mean of 3 years.
AB  - BACKGROUND: Fixation of proximal humeral fractures (PHF) with locking plates has
      gained popularity over conservative treatment, but surgery may be complicated
      with infection, non-union, avascular necrosis (AVN) of the humeral head and
      fixation failure. Failure to achieve structural support of the medial column has
      been suggested to be an important risk factor for fixation failure. The aims of
      this study were to examine the effect of calcar screws and fracture reduction on
      the risk of fixation failure and to assess long-term shoulder pain and function.
      METHODS: This was a single-centre retrospective study of 190 adult PHF patients
      treated with a locking plate between 2011 and 2014. Reoperations due to fixation
      failure were the primary outcome. Risk factors for fixation failure were assessed
      using the Cox regression analysis. Postoperative shoulder pain and function were
      assessed by the Oxford Shoulder Score (OSS). RESULTS: Thirty-one of 190 (16%)
      patients underwent a reoperation: 14 (7%) due to fixation failure, 10 (5%) due to
      deep infection and 2 (1%) due to AVN. The absence of calcar screws and fixation
      with residual varus malalignment (head-shaft angle < 120 degrees ) both increased
      the risk of fixation failure with an adjusted hazard ratio (95% CI) of 8.6 (1.9
      39.3; p = 0.005) and 4.9 (1.3-17.9; p = 0.02), respectively. The median
      (interquartile range) OSS was 40 (27-46). CONCLUSION: The use of calcar screws,
      as well as the absence of postoperative varus malalignment, significantly reduced
      the risk of fixation failure. We, therefore, recommend the use of calcar screws
      and to avoid residual varus malalignment to improve the medial support of
      proximal humeral fractures treated with a locking plate.

PMID- 30092808
TI  - Acetosyringone treatment duration affects large T-DNA molecule transfer to rice
      callus.
AB  - BACKGROUND: Large T-DNA fragment transfer has long been a problem for
      Agrobacterium-mediated transformation. Although vector systems, such as the BIBAC
      series, were successfully developed for the purpose, low transformation
      efficiencies were consistently observed. RESULTS: To gain insights of this
      problem in monocot transformation, we investigated the T-strand accumulation of
      various size of T-DNA in two kinds of binary vectors (one copy vs. multi-copy)
      upon acetosyringone (AS) induction and explored ways to improve the efficiency of
      the large T-DNA fragment transfer in Agrobacterium-mediated rice transformation.
      By performing immuno-precipitation of VirD2-T-strands and quantitative real-time
      PCR assays, we monitored the accumulation of the T-strands in Agrobacterium
      tumeficiens after AS induction. We further demonstrated that extension of AS
      induction time highly significantly improved large-size T-DNA transfer to rice
      cells. CONCLUSIONS: Our data provide valuable information of the T-strand
      dynamics and its impact on large T-DNA transfer in monocots, and likely dicots as
      well.

PMID- 30092809
TI  - Fate of the UPR marker protein Kar2/Bip and autophagic processes in fed-batch
      cultures of secretory insulin precursor producing Pichia pastoris.
AB  - BACKGROUND: Secretory recombinant protein production with Pichia (syn.
      Komagataella) pastoris is commonly associated with the induction of an unfolded
      protein response (UPR) usually apparent through increased intracellular levels of
      endoplasmic reticulum (ER) resident chaperones such as Kar2/Bip. During methanol
      induced secretory production of an insulin precursor (IP) under industrially
      relevant fed-batch conditions the initially high level of intracellular Kar2/Bip
      after batch growth on glycerol unexpectedly declined in the following methanol
      fed-batch phase misleadingly suggesting that IP production had a low impact on
      UPR activation. RESULTS: Analysis of the protein production independent level of
      Kar2/Bip revealed that high Kar2/Bip levels were reached in the exponential
      growth phase of glycerol batch cultures followed by a strong decline of Kar2/Bip
      during entry into stationary phase. Ultra-structural cell morphology studies
      revealed autophagic processes (e.g. ER phagy) at the end of the glycerol batch
      phase most likely responsible for the degradation of ER resident chaperones such
      as Kar2/Bip. The pre-induction level of Kar2/Bip did not affect the IP secretion
      efficiency in the subsequent methanol-induced IP production phase. During growth
      on methanol intracellular Kar2/Bip levels declined in IP producing and non
      producing host cells. However, extracellular accumulation of Kar2/Bip was
      observed in IP-producing cultures but not in non-producing controls. Most
      importantly, the majority of the extracellular Kar2/Bip accumulated in the
      culture supernatant of IP producing cells as truncated protein (approx. 35 kDa).
      CONCLUSIONS: Rapid growth leads to higher basal levels of the major UPR marker
      protein Kar2/Bip independent of recombinant protein production. Entry into
      stationary phase or slower growth on poorer substrate, e.g. methanol, leads to a
      lower basal Kar2/Bip level. Methanol-induced secretory IP production elicits a
      strong UPR activation which counteracts the reduced UPR during slow growth on
      methanol. The major ER chaperone Kar2/Bip is found together with recombinant IP
      in the culture medium where full-length Kar2/Bip accumulates in addition to large
      amounts of truncated Kar2/Bip. Thus, for judging UPR activating properties of the
      produced protein it is important to additionally analyze the medium not only for
      intact Kar2/Bip but also for truncated versions of this UPR reporter protein.

PMID- 30092811
TI  - Oppression, liberation, wellbeing, and ecology: organizing metaphors for
      understanding health workforce migration and other social determinants of health.
AB  - BACKGROUND: The Commission on Social Determinants of Health (CSDH) identifies the
      maldistribution of power, money, and resources as main drivers of health
      inequities. The CSDH further observes that tackling these drivers effectively
      requires interventions to focus at local, national, and global levels. Consistent
      with the CSDH's observation, this paper describes the eco-psychopolitical
      validity (EPV) paradigm, a multilevel and transdisciplinary model for research
      and action, thus far insufficiently tapped, but with the potential to systematize
      the exploration of the social determinants of health. RESULTS: Using the
      physician migration from Sub-Saharan Africa (SSA) to the United States as
      illustration, this paper articulates how the EPV model can be applied to the
      systematic analysis of a complex social problem with health inequity
      implications. To help explore potential determinants of physician migration, a
      comprehensive coding matrix is developed; with the organizing metaphors of the
      EPV model-namely oppression, liberation, and wellbeing-serving as analytical
      categories. Through the lens of the EPV model, migrating physicians are revealed
      as both ecological subjects enmeshed in a vast web of transnational processes
      linking source and destination countries, and potential change agents pursuing
      liberation and wellbeing. While migration may expand the opportunities of emigre
      physicians, it is argued that, the pursuit of wellbeing by way of migration
      cannot fully materialize abroad without some efforts to return home, physically
      or socially. CONCLUSION: Clarifying the relationship between various social
      determinants of health and health inequities at different levels of analysis is a
      more complex but essential endeavor to knowledge generation than using a one
      dimensional frame. With its roots in interdisciplinary thinking and its emphasis
      on both individual and contextual factors, the EPV paradigm holds promise as a
      model for examining the social determinants of health.

PMID- 30092810
TI  - Immunotherapy targeting toll-like receptor 2 alleviates neurodegeneration in
      models of synucleinopathy by modulating alpha-synuclein transmission and
      neuroinflammation.
AB  - BACKGROUND: Synucleinopathies of the aging population are an heterogeneous group
      of neurological disorders that includes Parkinson's disease (PD) and dementia
      with Lewy bodies (DLB) and are characterized by the progressive accumulation of
      alpha-synuclein in neuronal and glial cells. Toll-like receptor 2 (TLR2), a
      pattern recognition immune receptor, has been implicated in the pathogenesis of
      synucleinopathies because TLR2 is elevated in the brains of patients with PD and
      TLR2 is a mediator of the neurotoxic and pro-inflammatory effects of
      extracellular alpha-synuclein aggregates. Therefore, blocking TLR2 might
      alleviate alpha-synuclein pathological and functional effects. For this purpose,
      herein, we targeted TLR2 using a functional inhibitory antibody (anti-TLR2).
      METHODS: Two different human alpha-synuclein overexpressing transgenic mice were
      used in this study. alpha-synuclein low expresser mouse (alpha-syn-tg, under the
      PDGFbeta promoter, D line) was stereotaxically injected with TLR2 overexpressing
      lentivirus to demonstrate that increment of TLR2 expression triggers
      neurotoxicity and neuroinflammation. alpha-synuclein high expresser mouse (alpha
      Syn-tg; under mThy1 promoter, Line 61) was administrated with anti-TLR2 to
      examine that functional inhibition of TLR2 ameliorates neuropathology and
      behavioral defect in the synucleinopathy animal model. In vitro alpha-synuclein
      transmission live cell monitoring system was used to evaluate the role of TLR2 in
      alpha-synuclein cell-to-cell transmission. RESULTS: We demonstrated that
      administration of anti-TLR2 alleviated alpha-synuclein accumulation in neuronal
      and astroglial cells, neuroinflammation, neurodegeneration, and behavioral
      deficits in an alpha-synuclein tg mouse model of PD/DLB. Moreover, in vitro
      studies with neuronal and astroglial cells showed that the neuroprotective
      effects of anti-TLR2 antibody were mediated by blocking the neuron-to-neuron and
      neuron-to-astrocyte alpha-synuclein transmission which otherwise promotes
      NFkappaB dependent pro-inflammatory responses. CONCLUSION: This study proposes
      TLR2 immunotherapy as a novel therapeutic strategy for synucleinopathies of the
      aging population.

PMID- 30092812
TI  - EGFR mutation status in Tunisian non-small-cell lung cancer patients evaluated by
      mutation-specific immunohistochemistry.
AB  - BACKGROUND: Screening mutations in epidermal growth factor receptor (EGFR) to
      analyze non-small-cell lung cancer (NSCLC) profile is the criterion to choose the
      best therapeutic strategy. New Oncology guidelines recommend EGFR mutation
      analysis before prescribing tyrosine kinase inhibitors (TKIs) treatment. Majority
      of lung cancer patients are diagnosed at advanced stages and generally only small
      biopsies materials are available for diagnostic and molecular characterization.
      The aim of this first work is to screen EGFR mutation status in Tunisian NSCLC by
      mutation-specific immunohistochemistry (IHC) and molecular biology, to estimate
      the relevance of proposing TKIs as a new therapeutic line. METHODS: E746-A750
      deletion and L858R mutations were screened in 50 unselected NSCLC formalin-fixed
      paraffin-embedded (FFPE) tissue samples. Mutation expression by IHC was evaluated
      by intensity and percentage of staining and correlated to patients' data. DNA was
      extracted and EGFR mutations were analyzed by Sanger sequencing. Positive and
      negative controls were included for EGFR mutations in order to support the
      results. RESULTS: Among our patients (48 men and 2 women) all adenocarcinoma
      (confirmed by histology and IHC with TTF1/Napsin A), 94% were smokers exceeding
      the tobacco risk threshold (at least 25 pack-years) and the women were none. 44%
      had EGFR mutation by IHC: 26% had simple mutation and 18% had concurrent
      mutation. All mutated cases were smokers except a woman who was none. Concurrent
      mutations patients exceeded 40 pack-years. 91.4% of IHC results were validated by
      molecular analysis (100% of negative and 85% of positive cases) showing either T
      > G (exon 21) or 2235-2249 del (exon 19). CONCLUSIONS: These preliminary results
      confirm the usefulness of IHC to detect EGFR mutations but the frequency of
      concurrent mutations doesn't appear in favor of EGFR TKIs treatment. In fact,
      literature reports a significantly worse response compared to those with single
      mutation when treated by TKIs.

PMID- 30092813
TI  - Smith-Lemli-Opitz syndrome presenting as acute adrenal crisis in a child: a case
      report.
AB  - BACKGROUND: Smith-Lemli-Opitz syndrome is a rare autosomal recessive disorder of
      cholesterol biosynthesis which is characterized by multiple congenital
      malformations and global developmental delay. Here we report the case of a 3-year
      old, previously undiagnosed, child with Smith-Lemli-Opitz syndrome presenting
      with acute adrenal crisis, which is an extremely rare and atypical presentation
      of this disease. CASE PRESENTATION: A 3-year-old Sri Lankan Sinhalese boy without
      evidence of infection presented with circulatory collapse. He had a normal
      perinatal period; however, his early infancy was complicated by poor feeding,
      episodes of loose stools, failure to thrive, and several episodes of unexplained
      drowsiness. His weight, height, and occipitofrontal circumference were well below
      the third percentile. He had soft dysmorphic features that included microcephaly,
      bitemporal narrowing, upward slanting eyes, epicanthal folds, partial ptosis,
      broad nasal bridge, low set posteriorly rotated ears, high arched palate, and
      short neck. Marked hyperpigmentation was noted in perioral, buccal, and palmar
      areas. His pulses were rapid and low in volume and his systolic blood pressure
      was low. Initial resuscitation was performed by administering multiple
      crystalloid fluid boluses. A septic screen was negative. His blood glucose and
      serum bicarbonate levels were low and serum electrolytes revealed hyponatremia
      with hyperkalemia. Serum spot cortisol level was low normal and 17
      hydroxyprogesterone level was low. Diagnosis of Smith-Lemli-Opitz syndrome and
      associated adrenal crisis was made based on clinical and biochemical features.
      Intravenously administered hydrocortisone was commenced to which he showed a
      marked clinical response. CONCLUSIONS: This case describes a rare and atypical
      presentation of Smith-Lemli-Opitz syndrome and highlights the importance of
      making early and accurate syndromic diagnoses in children with dysmorphism to
      avoid sudden and life-threatening complications.

PMID- 30092814
TI  - Mediterranean diet and risk of rheumatoid arthritis: a population-based case
      control study.
AB  - BACKGROUND: The Mediterranean diet has been associated with lower mortality and
      lower risk of cardiovascular diseases and cancer. Although its components have
      been analysed in several studies, only one study has specifically investigated
      the association between Mediterranean diet and risk of rheumatoid arthritis (RA),
      and reported no association. METHODS: Data on 1721 patients with incident RA
      (cases) and 3667 controls, matched on age, gender and residential area, from the
      Swedish epidemiological investigation of RA (EIRA), a population-based case
      control study, were analysed using conditional logistic regression. The
      Mediterranean diet score, ranging from 0 to 9, was calculated from a 124-item
      food frequency questionnaire. RESULTS: In the EIRA study (median age of
      participants 53 years), 24.1% of the patients and 28.2% of the controls had high
      adherence to the Mediterranean diet (a score between 6 and 9). After adjustments
      for body mass index, educational level, physical activity, use of dietary
      supplements, energy intake, and smoking, high adherence reduced the odds of
      developing RA by 21% (OR 0.79; 95% CI 0.65-0.96) as compared to low adherence (a
      score between 0 and 2). The OR was even lower among men (OR 0.49; 95% CI 0.33
      0.73), but no significant association was found among women (OR 0.94; 95% CI 0.74
      1.18). An association between high diet score and low risk of RA was observed in
      rheumatoid factor (RF)-positive (OR 0.69; 95% CI 0.54-0.88), but not RF-negative
      RA (OR 0.96; 95% CI 0.68-1.34), and in RA characterised by presence of antibodies
      to citrullinated peptides (ACPA), but not in ACPA-negative RA. CONCLUSIONS: In
      this large population-based case-control study, the Mediterranean diet score was
      inversely associated with risk of RA. However, an association was only found
      among men and only in seropositive RA.

PMID- 30092815
TI  - IDTAXA: a novel approach for accurate taxonomic classification of microbiome
      sequences.
AB  - BACKGROUND: Microbiome studies often involve sequencing a marker gene to identify
      the microorganisms in samples of interest. Sequence classification is a critical
      component of this process, whereby sequences are assigned to a reference taxonomy
      containing known sequence representatives of many microbial groups. Previous
      studies have shown that existing classification programs often assign sequences
      to reference groups even if they belong to novel taxonomic groups that are absent
      from the reference taxonomy. This high rate of "over classification" is
      particularly detrimental in microbiome studies because reference taxonomies are
      far from comprehensive. RESULTS: Here, we introduce IDTAXA, a novel approach to
      taxonomic classification that employs principles from machine learning to reduce
      over classification errors. Using multiple reference taxonomies, we demonstrate
      that IDTAXA has higher accuracy than popular classifiers such as BLAST, MAPSeq,
      QIIME, SINTAX, SPINGO, and the RDP Classifier. Similarly, IDTAXA yields far fewer
      over classifications on Illumina mock microbial community data when the expected
      taxa are absent from the training set. Furthermore, IDTAXA offers many practical
      advantages over other classifiers, such as maintaining low error rates across
      varying input sequence lengths and withholding classifications from input
      sequences composed of random nucleotides or repeats. CONCLUSIONS: IDTAXA's
      classifications may lead to different conclusions in microbiome studies because
      of the substantially reduced number of taxa that are incorrectly identified
      through over classification. Although misclassification error is relatively
      minor, we believe that many remaining misclassifications are likely caused by
      errors in the reference taxonomy. We describe how IDTAXA is able to identify many
      putative mislabeling errors in reference taxonomies, enabling training sets to be
      automatically corrected by eliminating spurious sequences. IDTAXA is part of the
      DECIPHER package for the R programming language, available through the
      Bioconductor repository or accessible online ( http://DECIPHER.codes ).

PMID- 30092816
TI  - Climate drivers of vector-borne diseases in Africa and their relevance to control
      programmes.
AB  - BACKGROUND: Climate-based disease forecasting has been proposed as a potential
      tool in climate change adaptation for the health sector. Here we explore the
      relevance of climate data, drivers and predictions for vector-borne disease
      control efforts in Africa. METHODS: Using data from a number of sources we
      explore rainfall and temperature across the African continent, from seasonality
      to variability at annual, multi-decadal and timescales consistent with climate
      change. We give particular attention to three regions defined as WHO-TDR study
      zones in Western, Eastern and Southern Africa. Our analyses include 1) time scale
      decomposition to establish the relative importance of year-to-year, decadal and
      long term trends in rainfall and temperature; 2) the impact of the El Nino
      Southern Oscillation (ENSO) on rainfall and temperature at the Pan African scale;
      3) the impact of ENSO on the climate of Tanzania using high resolution climate
      products and 4) the potential predictability of the climate in different regions
      and seasons using Generalized Relative Operating Characteristics. We use these
      analyses to review the relevance of climate forecasts for applications in vector
      borne disease control across the continent. RESULTS: Timescale decomposition
      revealed long term warming in all three regions of Africa - at the level of 0.1
      0.3  degrees C per decade. Decadal variations in rainfall were apparent in all
      regions and particularly pronounced in the Sahel and during the East African long
      rains (March-May). Year-to-year variability in both rainfall and temperature, in
      part associated with ENSO, were the dominant signal for climate variations on any
      timescale. Observed climate data and seasonal climate forecasts were identified
      as the most relevant sources of climate information for use in early warning
      systems for vector-borne diseases but the latter varied in skill by region and
      season. CONCLUSIONS: Adaptation to the vector-borne disease risks of climate
      variability and change is a priority for government and civil society in African
      countries. Understanding rainfall and temperature variations and trends at
      multiple timescales and their potential predictability is a necessary first step
      in the incorporation of relevant climate information into vector-borne disease
      control decision-making.

PMID- 30092818
TI  - The role of the Wnt/beta-catenin signaling pathway in the proliferation of gold
      nanoparticle-treated human periodontal ligament stem cells.
AB  - BACKGROUND: Several studies have confirmed that gold nanoparticles (AuNPs) of
      specific concentration and size exert a boosting effect on cell proliferation;
      however, the mechanism through which this effect occurs remains unknown. This
      study explores the canonical Wnt signaling pathway in AuNP promotion of human
      periodontal ligament stem cell (hPDLSC) proliferation. METHODS: MTS was employed
      to evaluate hPDLSC proliferation. The interference of LRP5 and beta-catenin was
      steered by shRNA plasmids and siRNA, respectively, at which point the expression
      of MYC, CCND1, AXIN2, and POU5F1 had been estimated via real-time PCR. The
      expressions of LRP5 and beta-catenin were detected via western blot assay.
      RESULTS: The proliferation of hPDLSCs treated with 60 nm AuNPs at 56 MUM was
      clearly elevated. In contrast, beta-catenin siRNA significantly decreased cell
      viability. The LRP5 shRNA plasmid did not consistently impact cells. The
      expressions of these four genes downstream of the Wnt/beta-catenin signaling
      pathway were not significantly overexpressed in response to the interference of
      shRNA plasmid/siRNA with the treatment of AuNPs. CONCLUSIONS: These results
      suggest that the Wnt/beta-catenin signaling pathway plays a significant role in
      the process of AuNP promotion of hPDLSC proliferation.

PMID- 30092817
TI  - Volumetric breast density and risk of advanced cancers after a negative screening
      episode: a cohort study.
AB  - BACKGROUND: We evaluated the association between volumetric breast density (BD)
      and risk of advanced cancers after a negative screening episode. METHODS: A
      cohort of 16,752 women aged 49-54 years at their first screening mammography in
      the Florence screening programme was followed for breast cancer (BC) incidence
      until the second screening round. Volumetric BD was measured using fully
      automated software. The cumulative incidence of advanced cancer after a negative
      screening episode (including stage II or more severe cancer during the screening
      interval - on average 28 months - and at the subsequent round) was calculated
      separately for Volpara density grade (VDG) categories. RESULTS: BC incidence
      gradually increased with the increas in BD: 3.70/00, 5.10/00, 5.40/00 and 9.10/00
      in the VDG categories 1-4, respectively (p trend < 0.001). The risk of advanced
      cancers after a negative screening episode was 1.00/00, 1.30/00, 1.10/00, and
      4.20/00 (p trend = 0.003). The highest BD category, compared with the other three
      together, has double the invasive BC risk (RR = 2.0; 95% CI 1.5-2.8) and almost
      fourfold risk of advanced cancer (RR = 3.8; 95% CI 1.8-8.0). CONCLUSION: BD has a
      strong impact on the risk of advanced cancers after a negative screening episode,
      the best early surrogate of BC mortality. Therefore, our results suggest that
      screening effectiveness is quite different among BD categories.

PMID- 30092819
TI  - Exosomes derived from human adipose mesenchymal stem cells improve ovary function
      of premature ovarian insufficiency by targeting SMAD.
AB  - BACKGROUND: Although many reports show that various kinds of stem cells have the
      ability to recover the function of premature ovarian insufficiency (POI), few
      studies are associated with the mechanism of stem cell treatment of POI. We
      designed this experimental study to investigate whether human adipose stem cell
      derived exosomes (hADSC-Exos) retain the ability to restore ovarian function and
      how hADSC-Exos work in this process. METHODS: A POI mouse model was established
      and human ovarian granule cells (hGCs) collected from individuals with POI were
      prepared to assess the therapeutic effects and illuminate the mechanism of hADSCs
      in curing POI. The hematoxylin and eosin assay method was employed to assess the
      number of follicles. Enzyme-linked immunosorbent assay (ELISA) was used to detect
      the serum levels of sex hormones. The proliferation rate and marker expression
      levels of hGCs were measured by flow cytometry (fluorescence-activated cell
      sorting). Real-time PCR and western blot assays were used to determine the mRNA
      and protein expression levels of SMAD2, SMAD3, and SMAD5. Western blot assays
      were used to test the protein expression levels of apoptosis genes (Fas, FasL,
      caspase-3, and caspase-8). RESULTS: After the hADSC-Exos were transplanted into
      the POI mice model, they exerted better therapeutic activity on mouse ovarian
      function, improving follicle numbers during four stages. ELISA results showed
      that hADSC-Exos elevated the hormone levels to the normal levels. In addition,
      after hADSC-Exos were cocultured with POI hGCs, our results showed that hADSC
      Exos significantly promoted the proliferation rate and inhibited the apoptosis
      rate. Furthermore, hADSC-Exos also increased the marker expression of hGCs to the
      normal level. Besides, mRNA and protein assays demonstrated that hADSC-Exos
      downregulated the expression of SMAD2, SMAD3, and SMAD5 in vivo and in vitro.
      Western blot assay demonstrated that hADSC-Exos inhibited expression of the
      apoptosis genes in POI hGCs, and SMAD knockdown increased the protein expression
      of apoptosis genes. CONCLUSIONS: These findings demonstrate for the first time
      the molecular cascade and related cell biology events involved in the mechanism
      by which exosomes derived from hADSCs improved ovarian function of POI disease
      via regulation of the SMAD signaling pathway.

PMID- 30092820
TI  - Adipose tissue-derived extracellular fraction characterization: biological and
      clinical considerations in regenerative medicine.
AB  - BACKGROUND: Adipose tissue-derived stem cells are considered to be a promising
      source in the field of cell therapy and regenerative medicine. In addition to
      direct cell replacement using adipose tissue or purified stem cells,
      intercellular molecule exchange by the adipose tissue complex, a vast array of
      bioactive secretory factors, demonstrated beneficial effects by reducing tissue
      damage and stimulation of endogenous repair. However, for therapeutic purposes,
      the use of secretome derivatives, such as full conditioned media or purified
      exosomes generated in vitro, may present considerable disadvantages for cell
      manufacturing, storage, product safety, and their potential as a ready-to-go
      therapeutic product. METHODS: In this study, the effect of a liquid fraction of
      lipoaspirates isolated intraoperatively from 28 healthy donors was evaluated for
      their protective effect against oxidative stress and senescence, proliferation,
      and migration in vitro on normal human melanocytes, keratinocytes, and
      fibroblasts. Immunoenzymatic quantification of several growth factors and
      important signal molecules was used to define the biological profile of
      physiological adipose tissue secretome. RESULTS: Adipose tissue extracellular
      fraction (AT-Ex), isolated from lipoaspirate, exhibited significant potential for
      skin repair. AT-Ex augmented dermal and epidermal cell proliferation in a dose
      dependent manner without promoting cancer cell growth. Moreover, migration of
      dermal fibroblasts, an important phenomenon implicated in endogenous repair, was
      enhanced by AT-Ex treatment. AT-Ex has a positive impact on oxidative stress
      damage when cells are exposed to extrinsic hostile factors and prevent a
      fibroblast senescence phenotype including paracrine functions associated with
      skin aging. CONCLUSIONS: Collectively, our findings propose natural systems
      carrying the physiological balance of in-vivo produced secretome that could
      improve cutaneous wound healing and tissue repair. This approach, representing an
      innovative perspective and therapeutic strategy in regenerative medicine, could
      also be combined with autologous stem cell grafts to treat chronic nonhealing
      wounds, stable vitiligo, severe burns, and post-oncological scarring.

PMID- 30092821
TI  - Clonal relatedness in tumour pairs of breast cancer patients.
AB  - BACKGROUND: Molecular classification of tumour clonality is currently not
      evaluated in multiple invasive breast carcinomas, despite evidence suggesting
      common clonal origins. There is no consensus about which type of data (e.g. copy
      number, mutation, histology) and especially which statistical method is most
      suitable to distinguish clonal recurrences from independent primary tumours.
      METHODS: Thirty-seven invasive breast tumour pairs were stratified according to
      laterality and time interval between the diagnoses of the two tumours. In a multi
      omics approach, tumour clonality was analysed by integrating clinical
      characteristics (n = 37), DNA copy number (n = 37), DNA methylation (n = 8), gene
      expression microarray (n = 7), RNA sequencing (n = 3), and SNP genotyping data (n
      = 3). Different statistical methods, e.g. the diagnostic similarity index (SI),
      were used to classify the tumours as clonally related recurrences or independent
      primary tumours. RESULTS: The SI and hierarchical clustering showed similar
      tendencies and the highest concordance with the other methods. Concordant
      evidence for tumour clonality was found in 46% (17/37) of patients. Notably, no
      association was found between the current clinical guidelines and molecular
      tumour features. CONCLUSIONS: A more accurate classification of clonal
      relatedness between multiple breast tumours may help to mitigate treatment
      failure and relapse by integrating tumour-associated molecular features, clinical
      parameters, and statistical methods. Guidelines need to be defined with exact
      thresholds to standardise clonality testing in a routine diagnostic setting.

PMID- 30092823
TI  - Glutathione S-transferases play a role in the detoxification of flumethrin and
      chlorpyrifos in Haemaphysalis longicornis.
AB  - BACKGROUND: Haemaphysalis longicornis is a tick of importance to health, as it
      serves as a vector of several pathogens, including Theileria orientalis, Babesia
      ovata, Rickettsia japonica and the severe fever with thrombocytopenia syndrome
      virus (SFTSV). Presently, the major method of control for this tick is the use of
      chemical acaricides. The glutathione S-transferase (GST) system is one mechanism
      through which the tick metabolizes these acaricides. Two GSTs from H. longicornis
      (HlGST and HlGST2) have been previously identified. RESULTS: Enzyme kinetic
      studies were performed to determine the interaction of acaricides with
      recombinant H. longicornis GSTs. Recombinant HlGST activity was inhibited by
      flumethrin and cypermethrin, while recombinant HlGST2 activity was inhibited by
      chlorpyrifos and cypermethrin. Using real-time RT-PCR, the upregulation of the
      HlGST gene was observed upon exposure to sublethal doses of flumethrin, while the
      HlGST2 gene was upregulated when exposed to sublethal doses of chlorpyrifos. Sex
      and strain dependencies in the induction of GST gene expression by flumethrin
      were also observed. Knockdown of the HlGST gene resulted in the increased
      susceptibility of larvae and adult male ticks to sublethal doses of flumethrin
      and the susceptibility of larvae against sublethal doses of chlorpyrifos was
      increased upon knockdown of HlGST2. CONCLUSIONS: HlGST could be vital for the
      metabolism of flumethrin in larvae and adult male ticks, while HlGST2 is
      important in the detoxification of chlorpyrifos in larval ticks.

PMID- 30092824
TI  - Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung
      cancer and serves as a good prognostic predictor.
AB  - BACKGROUND: Lung cancer is the leading cause of cancer death worldwide. Recently,
      epigenetic dysregulation has been known to promote tumor progression and
      therefore may be a therapeutic target for anticancer therapy. JARID1B, a member
      of histone demethylases, has been found to be related to tumorigenesis in certain
      kinds of cancers. However, its biological roles in non-small cell lung cancer
      (NSCLC) remain largely unclear. METHODS: We firstly examined the expression of
      JARID1B in surgical specimens and six NSCLC cell lines. Then, we evaluated the
      relationship between JARID1B expression and clinicopathologic parameters in 72
      NSCLC patients, thereby established its prognostic importance. We subsequently
      studied the functional roles of JARID1B in tumorigenesis to verify its
      clinicopathologic significance. RESULTS: Our results showed that JARID1B was
      overexpressed in NSCLC cells and JARID1B overexpression was associated with tumor
      size, lymph node metastasis, advanced stages, and poor overall survival in NSCLC
      patients. JARID1B overexpression resulted in increased cell proliferation and
      formation of tumorspheres and correlated positively with the expression of cancer
      stem cells (CSCs) and epithelial-mesenchymal transition (EMT) markers, while the
      c-Met signaling pathway was actively involved. It also correlated with the
      strength of resistance to cisplatin and doxorubicin. On the contrary,
      downregulation of JARID1B expression by applying shRNA or JARID1B inhibitor PBIT
      reversed these phenomena. CONCLUSIONS: JARID1B worsens prognosis of NSCLC
      patients by promotion of tumor aggressiveness through multiple biological facets
      which were associated with activation of the c-Met signaling, and can be a novel
      prognostic biomarker and therapeutic target for NSCLC.

PMID- 30092822
TI  - Thyroid hormones and breast cancer association according to menopausal status and
      body mass index.
AB  - BACKGROUND: Thyroxine (T4) has been positively associated with tumor cell
      proliferation, while the effect of triiodothyronine (T3) on cell proliferation
      has not been well-established because it differs according to the type of cell
      line used. In Mexico, it has been reported that 14.5% of adult women have some
      type of thyroid dysfunction and abnormalities in thyroid function tests have been
      observed in a variety of non-thyroidal illnesses, including breast cancer (BC).
      These abnormalities might change with body mass index (BMI) because thyroid
      hormones are involved in the regulation of various metabolic pathways and
      probably by menopausal status because obesity has been negatively associated with
      BC in premenopausal women and has been positively associated with BC in
      postmenopausal women. METHODS: To assess the association between serum thyroid
      hormone concentration (T4 and T3) and BC and the influence of obesity as an
      effect modifier of this relationship in premenopausal and postmenopausal women,
      we measured serum thyroid hormone and thyroid antibody levels in 682 patients
      with incident breast cancer (cases) and 731 controls, who participated in a
      population-based case-control study performed from 2004 to 2007 in three states
      of Mexico. We tested the association of total T4 (TT4) and total T3 (TT3)
      stratifying by menopausal status and body mass index (BMI), and adjusted for
      other health and demographic risk factors using logistic regressions models.
      RESULTS: Higher serum total T4 (TT4) concentrations were associated with BC in
      both premenopausal (odds ratio (OR) per standard deviation = 5.98, 95% CI 3.01
      11.90) and postmenopausal women (OR per standard deviation = 2.81, 95% CI 2.17
      3.65). In premenopausal women, the effect of TT4 decreased as BMI increased while
      the opposite was observed in postmenopausal women. The significance of the effect
      modification was marginal (p = 0.059) in postmenopausal women and was not
      significant in premenopausal women (p = 0.22). Lower TT3 concentrations were
      associated with BC in both premenopausal and postmenopausal women and no effect
      modification was observed. CONCLUSIONS: There is a strong association between BC
      and serum concentrations of TT3 and TT4; this needs to be further investigated to
      understand why it happens and how important it is to consider these alterations
      in treatment.

PMID- 30092825
TI  - Epigenome-wide DNA methylation regulates cardinal pathological features of
      psoriasis.
AB  - BACKGROUND: Psoriasis is a chronic inflammatory autoimmune skin disorder. Several
      studies suggested psoriasis to be a complex multifactorial disease, but the exact
      triggering factor is yet to be determined. Evidences suggest that in addition to
      genetic factors, epigenetic reprogramming is also involved in psoriasis
      development. Major histopathological features, like increased proliferation and
      abnormal differentiation of keratinocytes, and immune cell infiltrations are
      characteristic marks of psoriatic skin lesions. Following therapy,
      histopathological features as well as aberrant DNA methylation reversed to normal
      levels. To understand the role of DNA methylation in regulating these crucial
      histopathologic features, we investigated the genome-wide DNA methylation profile
      of psoriasis patients with different histopathological features. RESULTS: Genome
      wide DNA methylation profiling of psoriatic and adjacent normal skin tissues
      identified several novel differentially methylated regions associated with
      psoriasis. Differentially methylated CpGs were significantly enriched in several
      psoriasis susceptibility (PSORS) regions and epigenetically regulated the
      expression of key pathogenic genes, even with low-CpG promoters. Top
      differentially methylated genes overlapped with PSORS regions including S100A9,
      SELENBP1, CARD14, KAZN and PTPN22 showed inverse correlation between methylation
      and gene expression. We identified differentially methylated genes associated
      with characteristic histopathological features in psoriasis. Psoriatic skin with
      Munro's microabscess, a distinctive feature in psoriasis including parakeratosis
      and neutrophil accumulation at the stratum corneum, was enriched with
      differentially methylated genes involved in neutrophil chemotaxis. Rete peg
      elongation and focal hypergranulosis were also associated with epigenetically
      regulated genes, supporting the reversible nature of these characteristic
      features during remission and relapse of the lesions. CONCLUSION: Our study, for
      the first time, indicated the possible involvement of DNA methylation in
      regulating the cardinal pathophysiological features in psoriasis. Common genes
      involved in regulation of these pathologies may be used to develop drugs for
      better clinical management of psoriasis.

PMID- 30092826
TI  - Ecological niche modeling predicting the potential distribution of Leishmania
      vectors in the Mediterranean basin: impact of climate change.
AB  - BACKGROUND: Due to climate change, the geographical distribution of sand flies
      during the last decades has shifted northward from latitudes below 45 degrees N
      in southern Europe to latitudes just above 50?N. Recent studies show that some
      phlebotomine sand flies were recorded in several parts of Germany and Belgium. In
      central Europe, some autochthone leishmaniasis cases are being recorded in
      regions traditionally regarded as leishmaniasis-free. An important challenge is
      to predict the geographical distribution of leishmaniasis vectors under new
      climatic conditions. In this study, we attempted to predict the current
      distribution of six leishmaniasis vectors in the Mediterranean basin and forecast
      species' geographical shift under future climate scenarios using an ensemble
      ecological niche modeling approach. Species records were obtained from scientific
      surveys published in the research literature between 2006 and 2016. A series of
      climate metrics describing temperature and precipitation in the study area under
      two climatic scenarios were obtained from WorldClim database. A consensus model
      was derived from six varieties of modeling approaches (regression, machine
      learning and classification techniques) in order to ensure valid prediction of
      distribution of vectors under different climate scenarios. RESULTS: Model
      performance was generally high for the included species with a specificity (true
      negative rate) ranging from 81.03 to 96.52% (mean = 86.94%) and a sensitivity
      (true positive rate) ranging from 87.93 to 100% (mean = 96.98%). Our work
      evidenced the hypothesis of the widespread of Leishmania vectors under climate
      change scenarios. All of the studied species are prospected to gain new areas
      that are actually not suitable for vectors' survival. Phlebotomine sand flies are
      prospected to invade extra-Mediterranean regions, especially western and central
      Europe. CONCLUSIONS: Our study confirmed the importance of environmental and
      climate factors on the distribution of leishmaniasis vectors and demonstrated the
      performance of ecological niche modeling in the prediction of the geographical
      spread of vector-borne diseases. Ecological niche modeling should be considered
      in the future as a valuable tool in addition to experimental laboratory studies
      for a better understanding of the biology of vector species.

PMID- 30092828
TI  - Analysis of differentially expressed genes among human hair follicle-derived
      iPSCs, induced hepatocyte-like cells, and primary hepatocytes.
AB  - BACKGROUND: Differentiation of human induced pluripotent stem cells (hiPSCs) into
      hepatocytes has important clinical significance in providing a new stem cell
      source for cell therapy of terminal liver disease. The differential gene
      expression analysis of hiPSCs, induced hepatocyte-like cells (HLCs), and primary
      human hepatocytes (PHHs) provides valuable information for optimization of an
      induction scheme and exploration of differentiation mechanisms. METHODS: Human
      hair follicle-derived iPSCs (hHF-iPSCs) were induced in vitro by mimicking the
      environment of a developing liver for 19 days. Expression of specific proteins
      was determined by immunofluorescence staining; the function of HLCs in storage
      and metabolism was identified by detecting periodic acid-Schiff, indocyanine
      green, and low-density lipoprotein. Based on the transcriptomics data, the
      differential gene expression profiles of hHF-iPSCs, HLCs, and PHHs were analyzed
      by Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, FunRich, and
      network analysis methods. RESULTS: HLCs were able to express albumin (ALB), alpha
      fetoprotein, CYP3A4, and CYP7A1, and exhibited matured liver cell functions such
      as glycogen synthesis and storage. Complement and coagulation cascades and
      metabolic pathways ranked top in the downregulated list of HLCs/PHHs, while the
      cell cycle ranked top in the upregulated list of HLCs/PHHs. In the protein
      protein interaction network, according to the degree rankings, TOP2A, CDK1, etc.
      were the important upregulated differentially expressed genes (DEGs), while ALB,
      ACACB, etc. were the major downregulated DEGs in HLCs/PHHs; the module analysis
      indicated that CDCA8, AURKB, and AURKA were the top upregulated DEGs in
      HLCs/PHHs. CONCLUSIONS: We presented the differences in gene expression among hHF
      iPSCs, HLCs, and PHHs through transcriptome array data and provided new ideas for
      the optimization of induction.

PMID- 30092829
TI  - Long-term exposure to insulin and volumetric mammographic density: observational
      and genetic associations in the Karma study.
AB  - BACKGROUND: Long-term insulin exposure has been implicated in breast cancer
      etiology, but epidemiological evidence remains inconclusive. The aims of this
      study were to investigate the association of insulin therapy with mammographic
      density (MD) as an intermediate phenotype for breast cancer and to assess
      associations with long-term elevated circulating insulin levels using a genetic
      score comprising 18 insulin-associated variants. METHODS: We used data from the
      KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort.
      Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237)
      diabetes were identified through linkage with the Prescribed Drug Register and
      age-matched to 1771 women without diabetes. We assessed associations with
      treatment duration and insulin glargine use, and we further examined MD
      differences using non-insulin-treated T2D patients as an active comparator. MD
      was measured using a fully automated volumetric method, and analyses were
      adjusted for multiple potential confounders. Associations with the insulin
      genetic score were assessed in 9437 study participants without diabetes. RESULTS:
      Compared with age-matched women without diabetes, insulin-treated T1D patients
      had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs.
      64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar
      associations were observed for insulin-treated T2D, and estimates were not
      materially different in analyses comparing insulin-treated T2D patients with T2D
      patients receiving noninsulin glucose-lowering medication. In both T1D and T2D,
      the magnitude of the association with the absolute dense volume was highest for
      long-term insulin therapy (>= 5 years) and the long-acting insulin analog
      glargine. No consistent evidence of differential associations by insulin
      treatment duration or type was found for percent dense and absolute nondense
      volumes. Genetically predicted insulin levels were positively associated with
      percent dense and absolute dense volumes, but not with the absolute nondense
      volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score
      = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [- 0.8; 0.9], respectively).
      CONCLUSIONS: The consistency in direction of association for insulin treatment
      and the insulin genetic score with the absolute dense volume suggest a causal
      influence of long-term increased insulin exposure on mammographic dense breast
      tissue.

PMID- 30092827
TI  - Induction of sustained remission in early inflammatory arthritis with the
      combination of infliximab plus methotrexate: the DINORA trial.
AB  - BACKGROUND: In the present study, we explored the effects of immediate induction
      therapy with the anti-tumour necrosis factor (TNF)alpha antibody infliximab (IFX)
      plus methotrexate (MTX) compared with MTX alone and with placebo (PL) in patients
      with very early inflammatory arthritis. METHODS: In an investigator-initiated,
      double-blind, randomised, placebo-controlled, multi-centre trial (ISRCTN21272423,
      http://www.isrctn.com/ISRCTN21272423 ), patients with synovitis of 12 weeks
      duration in at least two joints underwent 1 year of treatment with IFX in
      combination with MTX, MTX monotherapy, or PL randomised in a 2:2:1 ratio. The
      primary endpoint was clinical remission after 1 year (sustained for at least two
      consecutive visits 8 weeks apart) with remission defined as no swollen joints, 0
      2 tender joints, and an acute-phase reactant within the normal range. RESULTS:
      Ninety patients participated in the present study. At week 54 (primary endpoint),
      32% of the patients in the IFX + MTX group achieved sustained remission compared
      with 14% on MTX alone and 0% on PL. This difference (p < 0.05 over all three
      groups) was statistically significant for IFX + MTX vs PL (p < 0.05), but not for
      IFX + MTX vs MTX (p = 0.10), nor for MTX vs PL (p = 0.31). Remission was
      maintained during the second year on no therapy in 75% of the IFX + MTX patients
      compared with 20% of the MTX-only patients. CONCLUSIONS: These results indicate
      that patients with early arthritis can benefit from induction therapy with anti
      TNF plus MTX compared with MTX alone, suggesting that intensive treatment can
      alter the disease evolution. TRIAL REGISTRATION: The trial was registered at
      http://www.isrctn.com/ISRCTN21272423 on 4 October 2007 (date applied)/12 December
      2007 (date assigned). The first patient was included on 24 October 2007.

PMID- 30092830
TI  - New insights into the genic and metabolic characteristics of induced pluripotent
      stem cells from polycystic ovary syndrome women.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic
      disorder that affects female fertility. However, with the lack of a corresponding
      research model, the pathology mechanism of PCOS is poorly understood. Induced
      pluripotent stem cell (iPSC) technology has been recognized as means to generate
      patient-specific stem cells for disease modeling. METHODS: The mRNA abundance of
      iPSCs was analyzed by RNA microarray and real-time polymerase chain reaction (RT
      PCR). Karyotyping of iPSCs was performed with cytogenetic analysis. The
      mitochondrial respiration ability and glycolytic function were measured by the
      Seahorse Bioscience XF extracellular flux analyzer. The expression of iPSC
      associated markers was identified by immunofluorescence and RT-PCR. The teratoma
      formation of iPSCs was studied using immunochemistry. RESULTS: A PCOS patient
      derived iPSC model was established from somatic cells of PCOS patients. Through
      comprehensive transcriptional profiling analysis of the RNA microarray, PCOS
      patient-derived iPSCs showed metabolic abnormalities and mitochondrial
      dysfunction compared with non-PCOS patient-derived iPSCs in vitro . Specifically,
      a total of 2904 genes were differentially expressed between the two iPSC
      populations, of which 1416 genes were upregulated and 1488 genes were
      downregulated (fold change > 2, p < 0.01). Gene Ontology (GO) term enrichment
      results showed that upregulated genes were enriched in metabolic processes and
      mitochondrial activities which participated in the tricarboxylic acid (TCA)
      cycle, the respiratory electron transport chain (ETC), and glycogenolysis. On the
      other hand, the downregulated genes were related to cell communication, glucose
      transport, and uptake. The differentially expressed genes were verified by RT-PCR
      in PCOS patient-derived iPSCs and granulosa cells from PCOS patients. The PCOS
      patient-derived iPSCs demonstrated decreased mitochondrial respiration ability
      and glycolytic function (p < 0.05) but increased mitochondrial copy numbers and
      biogenesis (p < 0.05). Subsequently, some genes related to glucose metabolism
      were rescued by treating with metformin in PCOS patient-derived iPSCs. Meanwhile,
      the ATP production ability of mitochondria and the glycolysis ability of PCOS
      patient-derived iPSCs also partially returned to normal levels. However,
      metformin had little effect on mitochondrial maximal respiration ability and
      maximal glycolytic capacity. CONCLUSIONS: We measured differences in iPSCs from
      women with and without PCOS in gene transcription and mitochondrial respiratory
      function. PCOS patient-derived iPSCs showed abnormal expression of metabolic
      genes and mitochondrial dysfunction in vitro. The study provides a novel cell
      model in vitro for studying the clinical causes and molecular mechanisms of PCOS.

PMID- 30092831
TI  - The legacy effects of electromagnetic fields on bone marrow mesenchymal stem cell
      self-renewal and multiple differentiation potential.
AB  - BACKGROUND: The effects of electromagnetic fields (EMF) on bone nonunion have
      been reported for many years. Many studies and randomized controlled trials have
      demonstrated that EMF exhibited benefits in curing delayed union and nonunion of
      long bone fractures. Most of them focused on the immediate effects, while the
      legacy effects of EMF remain poorly investigated. METHODS: In this study, rat
      bone marrow mesenchymal stem cells (BMSCs) were treated with EMF, and after a
      period of time the BMSC proliferation and differentiation were detected.
      Additionally, BMSC sheets with or without EMF treatment were transplanted into
      the rat tibia fracture nonunion models. The bone formation was evaluated after 2,
      4, and 6 weeks. RESULTS: Our results showed that the proliferation capacity of
      BMSCs was heightened after EMF pretreatment. Over a period of time of EMF
      pretreatment, the capacities of osteogenic and chondrogenic differentiation were
      enhanced, while adipogenic differentiation was weakened. BMSC sheets pretreated
      with EMF could better promote the healing of tibia fracture in rats, compared to
      BMSC sheets alone. Furthermore, significantly higher values of radiographic
      grading scores were observed in the EMF group. CONCLUSIONS: EMF has lasting
      effects on the proliferation and differentiation of BMSCs, and together with cell
      sheet technology can provide a new method for the treatment of fracture nonunion.

PMID- 30092832
TI  - High mammographic density in women is associated with protumor inflammation.
AB  - BACKGROUND: Epidemiological studies have consistently shown that increased
      mammographic density (MD) is a strong risk factor for breast cancer. We
      previously observed an elevated number of vimentin+/CD45+ leukocytes in high MD
      (HMD) epithelium. In the present study, we aimed to investigate the subtypes of
      immune cell infiltrates in HMD and low MD (LMD) breast tissue. METHODS: Fifty
      four women undergoing prophylactic mastectomy at Peter MacCallum Cancer Centre or
      St. Vincent's Hospital were enrolled. Upon completion of mastectomy, HMD and LMD
      areas were resected under radiological guidance in collaboration with
      BreastScreen Victoria and were subsequently fixed, processed, and sectioned.
      Fifteen paired HMD and LMD specimens were further selected according to their
      fibroglandular characteristics (reasonable amount [> 20%] of tissue per block on
      H&E stains) for subsequent IHC analysis of immune cell infiltration. RESULTS:
      Overall, immune cell infiltrates were predominantly present in breast ducts and
      lobules rather than in the stroma, with CD68+ macrophages and CD20+ B lymphocytes
      also surrounding the vasculature. Macrophages, dendritic cells (DCs), B
      lymphocytes, and programmed cell death protein 1 (PD-1) expression were
      significantly increased in HMD epithelium compared with LMD. Moreover,
      significantly higher levels of DCs, CD4+ T cells, and PD-1 were also observed in
      HMD stroma than in LMD stroma. The increased expression of interleukin (IL)-6 and
      IL-4, with unaltered interferon-gamma, indicate a proinflammatory
      microenvironment. CONCLUSIONS: Our work indicates that the immune system may be
      activated very early in breast cancer development and may in part underpin the
      breast cancer risk associated with HMD.

PMID- 30092833
TI  - An exploration of the link between adult attachment and problematic Facebook use.
AB  - BACKGROUND: Previous studies have reported on positive and negative psychological
      outcomes associated with the use of social networking sites (SNSs). Research
      efforts linking Facebook use with depression and low self-esteem have indicated
      that it might be the manner in which people engage with the site that makes its
      use problematic for some people. The aim of the current study was to test a
      theoretical model of problematic Facebook use, using adult attachment style as
      the predictor variable of interest. METHOD: A cross-sectional design was employed
      wherein adult Facebook users (n = 717) completed measures of psychological
      distress, self-esteem, and adult attachment, in addition to measures of
      problematic Facebook use (i.e. social comparison, self-disclosures, impression
      management, & intrusive Facebook use). Data were analysed using hierarchical
      multiple regression and mediation analyses. RESULTS: The results of this study
      indicated that attachment anxiety was predictive of all facets of problematic
      Facebook use, and that attachment avoidance was predictive of impression
      management, and social consequences of intrusive Facebook use. Further analyses
      confirmed the mediating influences of psychological distress and self-esteem on
      these relationships. CONCLUSIONS: Users of Facebook with higher levels of
      attachment insecurity may be gravitating towards the site in order to fulfil
      their attachment needs. This tendency is likely to be particularly prevalent for
      those individuals with low self-esteem who are experiencing psychological
      distress.

PMID- 30092834
TI  - Development and characterization of a polarized human endometrial cell epithelia
      in an air-liquid interface state.
AB  - Human endometrial epithelia undergo injury repair and regeneration with the
      menstrual cycle; however, mechanisms underpinning the roles of endometrial
      epithelial cells in endometrial lesions and regeneration remain incompletely
      understood, mainly owing to the difficulty in the isolation and expansion of
      primary endometrial epithelial cells and the lack of reliable models for in vitro
      and in vivo studies. In this report, we sought to improve methods for the
      isolation and expansion of human endometrial epithelial cells with a Rho
      associated protein kinase (ROCK) inhibitor-modified medium and subsequently
      characterize endometrial epithelium generated with primary cells cultured in an
      air-liquid interface (ALI) state. Immunocytochemistry staining revealed the
      expression of epithelial cellular adhesion molecule (EpCam) and stage-specific
      embryonic antigen-1 (SSEA-1) but a lack of CD13 in endometrial epithelial cells.
      Meanwhile, a large number of proliferative Ki67+ cells were observed in isolated
      epithelial cells. Importantly, the EpCam+/CD13- cells were capable of forming
      spheroids, a characteristic of epithelial stem/progenitor cells. Interestingly,
      these cells also exhibited a capacity to reconstitute epithelial layers in an ALI
      state. Morphological analysis revealed mucosal secretion of differentiated
      epithelial cells with cilia and microvilli in ALI epithelial cells as determined
      by electronic microscopy. Immunoblotting assay further demonstrated the
      expression of endometrial epithelial cell markers keratin 17/19 and EpCam and
      stem cell marker OCT3/4 but not stromal cell marker Vimentin protein and CD13 in
      cell expansions. Furthermore, molecular analysis also showed that the exposure of
      cells to estrogen elevated the expression of estrogen receptor and progesterone
      receptors in ALI cultures. Our results shed light on the possibility of expanding
      sufficient numbers of endometrial epithelial cells for stem cell biology studies,
      and they provide a feasible and alternative model that can recapitulate the
      characteristics and physiology of endometrial epithelium in vivo.

PMID- 30092835
TI  - Polyfunctional anti-human epidermal growth factor receptor 3 (anti-HER3)
      antibodies induced by HER3 vaccines have multiple mechanisms of antitumor
      activity against therapy resistant and triple negative breast cancers.
AB  - BACKGROUND: Upregulation of human epidermal growth factor receptor 3 (HER3) is a
      major mechanism of acquired resistance to therapies targeting its
      heterodimerization partners epidermal growth factor receptor (EGFR) and human
      epidermal growth factor receptor 2 (HER2), but also exposes HER3 as a target for
      immune attack. We generated an adenovirus encoding full length human HER3 (Ad
      HER3) to serve as a cancer vaccine. Previously we reported the anti-tumor
      efficacy and function of the T cell response to this vaccine. We now provide a
      detailed assessment of the antitumor efficacy and functional mechanisms of the
      HER3 vaccine-induced antibodies (HER3-VIAs) in serum from mice immunized with Ad
      HER3. METHODS: Serum containing HER3-VIA was tested in complement-dependent
      cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) assays and
      for its effect on HER3 internalization and degradation, downstream signaling of
      HER3 heterodimers and growth of metastatic HER2+ (BT474M1), HER2 therapy
      resistant (rBT474), and triple negative (MDA-MB-468) breast cancers. RESULTS:
      HER3-VIAs mediated CDC and ADCC, HER3 internalization, interruption of HER3
      heterodimer-driven tumor signaling pathways, and anti-proliferative effects
      against HER2+ tumor cells in vitro and significant antitumor effects against
      metastatic HER2+ BT474M1, treatment refractory HER2+ rBT474 and triple negative
      MDA-MB-468 in vivo. CONCLUSIONS: In addition to the T cell anti-tumor response
      induced by Ad-HER3, the HER3-VIAs provide additional functions to eliminate
      tumors in which HER3 signaling mediates aggressive behavior or acquired
      resistance to HER2-targeted therapy. These data support clinical studies of
      vaccination against HER3 prior to or concomitantly with other therapies to
      prevent outgrowth of therapy-resistant HER2+ and triple negative clones.

PMID- 30092837
TI  - Beetles, ants, wasps, or flies? An ethnobiological study of edible insects among
      the Awajun Amerindians in Amazonas, Peru.
AB  - BACKGROUND: Insects are known to be able to provide valuable nutrients to
      indigenous populations across the Amazon. However, studies on traditional insect
      use in the Peruvian Amazon are scarce. This study documents edible insect
      diversity and characterizes their food and collection patterns in eight Awajun
      communities in the Peruvian Amazon. Additionally, we reviewed what has been known
      to date about the nutrient composition of the documented species. METHODS: The
      survey was conducted among the Awajun populations living in the Huampami, Paisa,
      Achu, and Tseasim communities in the Cenepa district and the Shijap, San Mateo,
      Kusu, and Listra communities in the Imaza district. Data collection was conducted
      through a freelisting exercise complemented by a semi-structured inquiry form in
      the Awajun language. In total, 104 informants (72 men and 32 women) aged between
      16 to 73 years were interviewed. RESULTS: The Awajun people use at least 12
      insect species, with Rhynchophorus palmarum, Atta cephalotes, and Rhinostomus
      barbirostris being the most important ones. Beetles of the family Curculionidae
      represent the culturally most salient taxon. In the more accessible and developed
      Imaza district, the Awajun tend to eat almost exclusively R. palmarum, while in
      the more isolated and preserved Cenepa district, the community's preferences are
      linked with more species. Although men are the main insect collectors, women
      cited more edible insects on average. The insects are eaten mainly roasted or
      raw. Further use patterns and differences between the districts are discussed.
      CONCLUSION: Traditional knowledge related to edible insects and the ecosystems
      they occur in is widespread among the Awajun populations, and insects still
      represent an important part of the indigenous food system. This ethnobiological
      survey discovered five species that are newly recorded as edible insects.
      Chemical composition of insects deemed edible by the Awajun ought to be analyzed
      in the future and awareness about their nutritional importance should be raised
      to harness the potential of this underutilized yet nutrient-rich traditional
      food.

PMID- 30092836
TI  - CNS-border associated macrophages respond to acute ischemic stroke attracting
      granulocytes and promoting vascular leakage.
AB  - The central nervous system (CNS) contains several types of immune cells located
      in specific anatomic compartments. Macrophages reside at the CNS borders
      surrounding the brain vessels, in leptomeningeal spaces and the choroid plexus,
      where they interact with the vasculature and play immunological surveillance and
      scavenging functions. We investigated the phenotypic changes and role of these
      macrophages in response to acute ischemic stroke. Given that CD163 expression is
      a hallmark of perivascular and meningeal macrophages in the rat and human brain,
      we isolated CD163+ brain macrophages by fluorescence activated cell sorting. We
      obtained CD163+ cells from control rats and 16 h following transient middle
      cerebral artery occlusion, after verifying that infiltration of CD163+ peripheral
      myeloid cells is negligible at this acute time point. Transcriptome analysis of
      the sorted CD163+ cells identified ischemia-induced upregulation of the hypoxia
      inducible factor-1 pathway and induction of genes encoding for extracellular
      matrix components and leukocyte chemoattractants, amongst others. Using a cell
      depletion strategy, we found that CNS border-associated macrophages participate
      in granulocyte recruitment, promote the expression of vascular endothelial growth
      factor (VEGF), increase the permeability of pial and cortical blood vessels, and
      contribute to neurological dysfunction in the acute phase of
      ischemia/reperfusion. We detected VEGF expression surrounding blood vessels and
      in some CD163+ perivascular macrophages in the brain tissue of ischemic stroke
      patients deceased one day after stroke onset. These findings show ischemia
      induced reprogramming of the gene expression profile of CD163+ macrophages that
      has a rapid impact on leukocyte chemotaxis and blood-brain barrier integrity, and
      promotes neurological impairment in the acute phase of stroke.

PMID- 30092838
TI  - Differential relationship between waist circumference and mortality according to
      age, sex, and body mass index in Korean with age of 30-90 years; a nationwide
      health insurance database study.
AB  - BACKGROUND: A recent concept is that obesity, assessed by body mass index (BMI),
      is not always a sign of poor health. Thus, in order to use obesity metrics in
      clinical decision making, it is important to clarify the relationship between
      waist circumference (WC), a proxy for abdominal obesity, and mortality. METHODS:
      Data were used from 8,796,759 subjects aged between 30 and 90 years, who had
      participated in the Korea National Health Screening Examination between January
      1, 2009 and December 31, 2009 and survived at least 1 year post screening. Data
      from a mean follow-up time of an additional 5.3 years (time at risk) were
      analyzed for the relationship between WC and mortality according to age, sex, and
      BMI category. RESULTS: An increased WC of more than 90 cm in men and 85 cm in
      women showed a definite negative influence on mortality. However, the detailed
      relationship between WC and mortality was J-shaped or U-shaped according to age,
      sex, and BMI category. In the normal BMI group, the optimal WC range with the
      lowest mortality was < 70 cm in men and 70-75 cm in women, whereas in obese
      individuals a WC between 80 and 90 cm in men and 75 and 85 cm in women showed the
      lowest mortality. The association between increased WC and higher mortality
      tended to be more obvious in normal-weight women than in normal-weight men or
      obese women. Furthermore, in normal-weight and obese women, the effect of
      increased WC on mortality was more critical for subjects aged < 60 years rather
      than those aged >= 60 years. CONCLUSIONS: Abdominal obesity, as measured by WC,
      showed a significant negative association on mortality, and its association with
      mortality was different according to age, sex, and BMI category. Therefore, WC
      should be considered in the assessment of obesity-related health risks, and
      individualized cut-off points for the definition of a healthy WC according to
      age, sex, and BMI category are necessary.

PMID- 30092839
TI  - Different curcumin forms selectively bind fibrillar amyloid beta in post mortem
      Alzheimer's disease brains: Implications for in-vivo diagnostics.
AB  - The combined fluorescent and Abeta-binding properties of the dietary spice
      curcumin could yield diagnostic purpose in the search for a non-invasive Abeta
      biomarker for Alzheimer's disease (AD). However, evidence on the binding
      properties of curcumin, its conjugates and clinically used bio-available
      formulations to AD neuropathological hallmarks is scarce. We therefore assessed
      the binding properties of different curcumin forms to different neuropathological
      deposits in post-mortem brain tissue of cases with AD, other neurodegenerative
      diseases, and controls. Post mortem brain tissue was histochemically assessed for
      the binding of curcumin, its isoforms, conjugates and bio-available forms and
      compared to routinely used staining methods. For this study we included brains of
      early onset AD, late onset AD, primary age-related tauopathy (PART), cerebral
      amyloid angiopathy (CAA), frontotemporal lobar degeneration (FTLD) with tau or
      TAR DNA-binding protein 43 (TDP-43) inclusions, dementia with Lewy bodies (DLB),
      Parkinson's disease (PD) and control cases without brain pathology. We found that
      curcumin binds to fibrillar amyloid beta (Abeta) in plaques and CAA. It does not
      specifically bind to inclusions of protein aggregates in FTLD-tau cases, TDP-43,
      or Lewy bodies. Curcumin isoforms, conjugates and bio-available forms show
      affinity for the same Abeta structures. Curcumin staining overlaps with
      immunohistochemical detection of Abeta in fibrillar plaques and CAA, and to a
      lesser extent cored plaques. A weak staining of neurofibrillary tangles was
      observed, while other structures immunopositive for phosphorylated tau remained
      negative. In conclusion, curcumin, its isoforms, conjugates and bio-available
      forms selectively bind fibrillar Abeta in plaques and CAA in post mortem AD brain
      tissue. Curcumin, being a food additive with fluorescent properties, is therefore
      an interesting candidate for in-vivo diagnostics in AD, for example in retinal
      fluorescent imaging.

PMID- 30092841
TI  - Investigation of myositis and scleroderma specific autoantibodies in patients
      with lung cancer.
AB  - BACKGROUND: The close temporal association between onset of some connective
      tissue diseases and cancer suggests a paraneoplastic association. Adult patients
      with scleroderma with anti-RNA polymerase III autoantibodies and adult patients
      with dermatomyositis with anti-transcriptional intermediary factor 1 (anti-TIF1)
      or anti-nuclear matrix protein 2 (anti-NXP2) autoantibodies have a significantly
      increased risk of developing cancer. Autoantibodies may serve as biomarkers for
      early detection of cancer and also could be relevant for prediction of responses
      to immune therapies. We aimed to test whether myositis and scleroderma specific
      or associated autoantibodies are detectable in individuals with lung cancer.
      METHODS: Serum from 60 Caucasian patients with lung cancer (30 with small cell
      lung cancer, 30 with non-small cell lung cancer) was screened for myositis and
      scleroderma specific and associated autoantibodies by radiolabelled
      immunoprecipitation. RESULTS: Anti-TIF1, anti-NXP2 or anti-RNA polymerase III
      autoantibodies were not detected in any of the 60 patients with lung cancer. Anti
      glycyl-transfer RNA (tRNA) synthetase (anti-EJ) autoantibodies were detected in
      one patient with non-small cell lung cancer. No other known myositis or
      scleroderma autoantibodies were identified. CONCLUSIONS: Myositis and scleroderma
      specific autoantibodies, including anti-TIF1, anti-NXP2 and anti-RNA polymerase
      III, are rare in patients with lung cancer without an autoimmune disease. We
      report here the first case of anti-EJ autoantibodies being detected in a patient
      with lung cancer without clinical or radiographic evidence of the anti-synthetase
      syndrome.

PMID- 30092842
TI  - Primary health Centres' performance assessment measures in developing countries:
      review of the empirical literature.
AB  - BACKGROUND: It is universally accepted that primary healthcare is essential for
      achieving public health and that assessment of its performance is critical for
      continuous improvement. The World Health Organization's (WHO's) framework for
      performance assessment is a comprehensive global standard, but difficult to apply
      in developing countries because of financial and data constraints. This study
      aims to review the empirical literature on measures for Primary Health Centre
      (PHC) performance assessment in developing countries, and compare them for
      comprehensiveness with the aspects described by the WHO Framework. METHODS:
      Research articles published in English scientific journals between January 1979
      and October 2016 were reviewed systematically. The reporting quality of the
      article and the quality of the measures were assessed with instruments adapted
      for the purpose of this study. Data was categorized and described. RESULTS:
      Fifteen articles were included in the study out of 4359 articles reviewed. Nine
      articles used quantitative methods, one article used qualitative methods
      exclusively and five used mixed methods. Fourteen articles had a good description
      of the measurement properties. None of the articles presented validity tests of
      the measures but eleven articles presented measures that were well established.
      Mostly studies included components of personnel competencies (skilled/ non
      skilled) and centre performance (patient satisfaction/cost /efficiency).
      CONCLUSIONS: In comparison to the WHO framework, the measures in the articles
      were limited in scope as they did not represent all service components of PHCs.
      Hence, PHC performance assessment should include system components along with
      relevant measures of personnel performance beyond knowledge of protocols.
      Existing measures for PHC performance assessment in developing countries need to
      be validated and concise measures for neglected aspects need to be developed.

PMID- 30092840
TI  - Cell therapy induced regeneration of severely atrophied mandibular bone in a
      clinical trial.
AB  - BACKGROUND: Autologous grafting, despite some disadvantages, is still considered
      the gold standard for reconstruction of maxillofacial bone defects. The aim of
      this study was to evaluate bone regeneration using bone marrow-derived
      mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach
      than autologous bone grafting. This comprehensive clinical trial included
      subjects with severe mandibular ridge resorption. METHODS: The study included 11
      subjects aged 52-79 years with severe mandibular ridge resorption. Bone marrow
      cells were aspirated from the posterior iliac crest and plastic adherent cells
      were expanded in culture medium containing human platelet lysate. The MSCs and
      biphasic calcium phosphate granules as scaffolds were inserted subperiosteally
      onto the resorbed alveolar ridge. After 4-6 months of healing, new bone formation
      was assessed clinically and radiographically, as were safety and feasibility.
      Bone at the implant site was biopsied for micro-computed topography and
      histological analyses and dental implants were placed in the newly regenerated
      bone. Functional outcomes and patient satisfaction were assessed after 12 months.
      RESULTS: The bone marrow cells, expanded in vitro and inserted into the defect
      together with biphasic calcium phosphate granules, induced significant new bone
      formation. The regenerated bone volume was adequate for dental implant
      installation. Healing was uneventful, without adverse events. The patients were
      satisfied with the esthetic and functional outcomes. No side effects were
      observed. CONCLUSIONS: The results of this comprehensive clinical trial in human
      subjects confirm that MSCs can successfully induce significant formation of new
      bone, with no untoward sequelae. Hence, this novel augmentation procedure
      warrants further investigation and may form the basis of a valid treatment
      protocol, challenging the current gold standard. TRIAL REGISTRATION: EudraCT,
      2012-003139-50. Registered on 21 August 2013. ClinicalTrials.gov, NCT 02751125 .
      Registered on 26 April 2016.

PMID- 30092843
TI  - Prospective randomized controlled trial to compare laparoscopic distal
      gastrectomy (D2 lymphadenectomy plus complete mesogastrium excision, D2 + CME)
      with conventional D2 lymphadenectomy for locally advanced gastric adenocarcinoma:
      study protocol for a randomized controlled trial.
AB  - BACKGROUND: Although radical gastrectomy with D2 lymph node dissection has become
      the standard surgical approach for locally advanced gastric cancer, patients
      still have a poor prognosis after operation. Previously, we proposed laparoscopic
      distal gastrectomy (D2 lymphadenectomy plus complete mesogastrium excision [D2 +
      CME]) as an optimized surgical procedure for locally advanced gastric cancer. By
      dissection along the boundary of the mesogastrium, D2 + CME resected proximal
      segments of the dorsal mesogastrium completely with less blood loss, and it
      improved the short-term surgical outcome. However, the oncologic therapeutic
      effect of D2 + CME has not yet been confirmed. METHODS/DESIGN: A single-center,
      prospective, parallel-group, randomized controlled trial of laparoscopic distal
      gastrectomy with D2 + CME versus conventional D2 was conducted for patients with
      locally advanced gastric cancer at Tongji Hospital, Wuhan, China. In total, 336
      patients who met the following eligibly criteria were included and were
      randomized to receive either the D2 + CME or D2 procedure: (1) pathologically
      proven adenocarcinoma; (2) 18 to 75 years old; cT2-4, N0-3, M0 at preoperative
      evaluation; (3) expected curative resection via laparoscopic distal gastrectomy;
      (4) no history of other cancer, chemotherapy, or radiotherapy; (5) no history of
      upper abdominal operation; and (6) perioperative American Society of
      Anesthesiologists class I, II, or III. The primary endpoint is 3 years of disease
      free survival. The secondary endpoints are overall survival, recurrence pattern,
      mortality, morbidity, postoperative recovery course, and other parameters.
      DISCUSSION: Previous studies have demonstrated the safety and feasibility of D2 +
      CME for locally advanced gastric cancer; however, there is still a lack of
      evidence to support its therapeutic effect. Thus, we performed this randomized
      trial to investigate whether D2 + CME can improve oncologic outcomes of patients
      with locally advanced gastric cancer. The findings from this trial may
      potentially optimize the surgical procedure and may improve the prognosis of
      patients with locally advanced gastric cancer. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT01978444 . Registered on October 31, 2013.

PMID- 30092844
TI  - 0Phobia - towards a virtual cure for acrophobia: study protocol for a randomized
      controlled trial.
AB  - BACKGROUND: Virtual reality exposure therapy (VRET) has been shown to be as
      effective as traditional forms of in vivo exposure therapy for the treatment of
      specific phobias. However, as with in vivo exposure, VRET still involves
      relatively high costs and limited accessibility which makes it prohibitive for a
      large part of the population. Innovative methods using smartphone applications
      (apps) may improve accessibility and scalability of VRET. The aim of this study
      is to evaluate 0Phobia, a gamified self-guided VRET for acrophobia that is
      delivered through a smartphone app in combination with rudimentary cardboard
      virtual reality (VR) goggles. METHODS/DESIGN: Participants (N = 180, aged 18-65
      years) with acrophobia symptoms will be recruited from the Dutch general
      population and randomized to either 0Phobia (n = 90) or a waitlist control
      condition (n = 90). 0Phobia will be delivered over a period of 3 weeks and
      includes psychoeducation, VR exposure, cognitive techniques, monitoring of
      symptoms, and relapse prevention. The primary outcome measure will be the
      Acrophobia Questionnaire. Secondary outcome measures will include user
      friendliness, symptoms of anxiety, depression, and mastery. Assessments will take
      place online at baseline, directly after the intervention (post test) and at
      follow-up (3 months). DISCUSSION: This study capitalizes on novel technology and
      recent scientific advances to develop an affordable and scalable treatment
      modality. TRIAL REGISTRATION: Netherlands Trial Register: NTR6442 . Registered on
      29 June 2017.

PMID- 30092845
TI  - Cytokine profiling in active and quiescent SLE reveals distinct patient
      subpopulations.
AB  - BACKGROUND: Patients with SLE display marked clinical and immunlogical
      heterogeneity. The purpose of the study was to investigate patterns of serum
      cytokines in patients with active and stable systemic lupus erythematosus (SLE)
      and to determine how they relate to clinical phenotype. METHODS: Serum levels of
      10 cytokines were measured retrospectively in a cohort of patients with SLE and
      in healthy controls using a high-sensitivity multiplex bead array. Disease
      activity was determined using the Systemic Lupus Erythematosus Disease Activity
      Index 2000 (SLEDAI-2K) and British Isles Lupus Assessment Group (BILAG-2004)
      indices. Logistic regression models were used to determine the association
      between cytokine levels and active SLE. Principal component analysis (PCA) and
      cluster analysis was then used to identify subgroups of patients on the basis of
      cytokine levels. RESULTS: Serum chemokine (C-X-C motif) ligand 10 (CXCL10) and
      CXCL13 were significantly higher in patients with SLE compared to healthy
      controls. Two cytokines (pentraxin-related protein (PTX3) and CXCL10) were
      significantly higher in patients with active disease after adjustment for
      potential confounding factors. Measurement of four cytokines (CXCL10, IL-10, IL
      21 and PTX3) significantly improved the performance of a model to identify
      patients with clinically active disease. Cluster analysis revealed that the
      patients formed 3 distinct groups, characterised by higher levels of interferon
      alpha (IFNalpha) and B lymphocyte stimulator (BLyS) (group 1), increased CXCL10
      and CXCL13 (group 2) or low levels of cytokines (group 3). Group 2 had
      significantly lower serum complement and higher anti-double-stranded DNA
      antibodies and increased prevalence of inflammatory arthritis. CONCLUSIONS:
      Multiplex analysis has identified a serum cytokine signature for active SLE.
      Within the SLE population distinct cytokine subgroups were identified, with
      differing clinical and immunological phenotypes that appeared stable over time.
      Assessment of cytokine profiles may reveal unique insights into disease
      heterogeneity.

PMID- 30092846
TI  - Breast fibroadenomas are not associated with increased breast cancer risk in an
      African American contemporary cohort of women with benign breast disease.
AB  - BACKGROUND: Fibroadenomas are common benign breast lesions, and studies of
      European American women indicate a persistent, increased risk of breast cancer
      after diagnosing a fibroadenoma on biopsy. This association has not been
      independently assessed in African American women, despite reports that these
      women are more likely to present with fibroadenomas. METHODS: The study cohort
      included 3853 African American women with a breast biopsy completed between 1997
      and 2010 in metropolitan Detroit. Biopsies were microscopically reviewed for
      benign breast lesions, including fibroadenoma, proliferative disease, and atypia.
      Risk of breast cancer within the cohort was estimated using relative risk ratios
      and 95% CIs calculated using multivariable log-binomial regression. Relative risk
      of breast cancer in this cohort compared with African American women in the
      broader metropolitan Detroit population was estimated using standardized
      incidence ratios (SIRs). RESULTS: Fibroadenomas occurred more frequently in
      biopsies of younger women, and other types of benign breast lesions were less
      likely to occur when a fibroadenoma was present (p = 0.008 for lobular
      hyperplasia; all other p values < 0.01). Unlike women with other benign lesions
      (SIR, 1.41; 95% CI, 1.20, 1.66), women with fibroadenomas did not have an
      increased risk of developing breast cancer compared with the general population
      (SIR, 0.94; 95% CI, 0.75, 1.18). Biopsies that indicated a fibroadenoma were
      associated with a reduced risk of breast cancer after adjusting for age at
      biopsy, proliferation, and atypia (relative risk, 0.67; 95% CI, 0.48, 0.93)
      compared with biopsies without a fibroadenoma. CONCLUSIONS: These findings have
      important implications for breast cancer risk models and clinical assessment,
      particularly among African American women, in whom fibroadenomas are common.

PMID- 30092847
TI  - Epigenetic modification of mesenchymal stromal cells enhances their suppressive
      effects on the Th17 responses of cells from rheumatoid arthritis patients.
AB  - BACKGROUND: The aim of this study was to investigate if epigenetically modified
      human mesenchymal stromal cells (hMSCs) can regulate the Th17-related immune
      responses. METHODS: We tested epigenetic drug combinations at various doses and
      selected the four combinations that resulted in maximal interleukin (IL)-10 and
      indoleamine 2,3-dioxygenase gene expression in hMSCs. We examined the effects of
      epigenetically modified hMSCs (epi-hMSCs) on CD4+ T-cell proliferation and
      inflammatory cytokine secretion under Th0- and Th17-polarizing conditions using
      mixed lymphocyte reactions and enzyme-linked immunosorbent assays (ELISAs). We
      determined Th17 cytokine levels and the percentage of Th17 cells among synovial
      fluid mononuclear cells (SFMCs) from rheumatoid arthritis (RA) patients by ELISA
      and flow cytometry. RESULTS: Epi-hMSCs inhibited the development of IL-17
      producing cells in culture. The percentages of IL-17+ and interferon (IFN)-gamma+
      cells among peripheral blood mononuclear cells from healthy donors were lower
      under both the Th0 and Th17 conditions in the presence of epi-hMSCs than in the
      presence of no or untreated hMSCs. Epi-hMSC-treated RA patient SFMCs secreted
      lower levels of IL-17 and IFN-gamma than RA patient SFMCs cultured without hMSCs
      or with untreated hMSCs. CONCLUSIONS: An optimal combination of hypomethylating
      agents and histone deacetylase inhibitors can enhance the immunomodulatory
      potential of hMSCs, which may be useful for RA treatment.

PMID- 30092849
TI  - Case-case analysis of Campylobacter and Salmonella - using surveillance data for
      outbreak investigations and monitoring routine risk factors.
AB  - Utilising routine surveillance data, this study presents a method for generating
      a baseline comparison that can be used in future foodborne outbreak
      investigations following a case-case methodology. Salmonella and Campylobacter
      cases (2012-2015) from Maricopa County, AZ were compared to determine differences
      in risk factors, symptoms and demographics. For foods and other risk factors,
      adjusted odds ratios were developed using Campylobacter as the reference.
      Comparisons were also made for three major Salmonella subtypes, Typhimurium,
      Enteritidis and Poona as compared with Campylobacter. Salmonella cases were
      younger, while Campylobacter cases were more Hispanic and female. Campylobacter
      cases reported consuming peppers, sprouts, poultry, queso fresco, eggs and raw
      nuts more and reported contact with animal products, birds, visiting a farm or
      dairy, owning a pet, a sick pet, swimming in a river, lake or pond, or handling
      multiple raw meats more. Salmonella cases reported visiting a petting zoo and
      contact with a reptile more. There were significant variations by Salmonella
      subtype in both foods and exposures. We recommend departments conduct this
      analysis to generate a baseline comparison and a running average of relevant odds
      ratios allowing staff to focus on trace-back of contaminated food items earlier
      in the outbreak investigation process.

PMID- 30092850
TI  - Association between Toxoplasma gondii exposure and paediatrics haematological
      malignancies: a case-control study.
AB  - The possible association between Toxoplasma gondii infection and paediatric
      haematological malignancies in a group of patients and control subjects was
      evaluated in the present study. We performed an age-, gender- and residence
      frequency-matched case-control study of 101 blood cancer patients under 18 years
      of age, all of which were treated in Amirkola Pediatric Hospital. One hundred and
      thirty-eight control samples were gathered from the outpatient clinic in the
      hospital. All cases and controls were tested for the presence of anti-Toxoplasma
      IgG antibodies and then IgG-positive subjects were evaluated for IgM antibodies
      by enzyme-linked immunoassays. Anti-T. gondii IgG antibodies were found in 37
      (36.6%) of the cases and 12 (8.7%) subjects in the control group (odds ratio
      6.07, 95% confidence interval 2.963-12.437, P < 0.0001). The median and
      interquartile range (IQR) of IgG titre from case group (7.7 (IQR 0.25-13.5)) was
      higher than the control (0.2 (IQR 0.1-0.5)) (P < 0.0001). The frequency of anti
      T. gondii antibodies (IgG) in lymphoblastic leukaemia (acute lymphoblastic
      leukaemia), Hodgkin's lymphoma and T-cell lymphoma were 33 (31.9%), 3 (50%) and
      1(100%), respectively. Anti-T. gondii IgM was not detected in the IgG-positive
      patients in case group. In the case subjects, no significant difference was seen
      in the positive rates of T. gondii infection between genders (37.3% in male;
      35.7% in female; P = 0.52) and ages groups (P = 0.31). This study demonstrated
      that T. gondii infection is prevalent in children with blood cancer. It also
      showed that toxoplasmosis may possibly be linked with an increased risk of
      childhood haematologic malignancies. Furthermore, these results may be helpful in
      research on blood neoplasia aetiology.

PMID- 30092848
TI  - Histone demethylase JMJD6 regulates cellular migration and proliferation in
      adipose-derived mesenchymal stem cells.
AB  - BACKGROUND: Adipose-derived mesenchymal stem cells (ADSCs) have been extensively
      explored as a promising therapeutic agent due to their differentiation,
      proliferation and migration abilities. The epigenetic mechanisms that regulate
      the fate of mesenchymal stem cells (MSCs) have been described in detail. However,
      the epigenetic modulation of ADSCs proliferation and migration is poorly
      understood. METHODS: The present study examined histone demethylases roles and
      expression by RT-PCR, as well as through siRNA screening and ChIP-qPCR assay.
      Cellular proliferation and migration assays were employed in shRNA-mediated JMJD6
      knockdown and control ADSCs. PDE1C inhibition studies were conducted to confirm
      its role in JMJD6-mediated epigenetic regulation of ADSCs. RESULTS: The data
      demonstrate that the histone demethylase JMJD6 plays a critical role in
      regulating the proliferation and migration of ADSCs by removing H4R3me2a at the
      promoter regions of PDEC1 and suppressing PDEC1 expression. Importantly, the
      depletion of JMJD6 in ADSCs significantly increased cellular proliferation and
      motility, which was associated with increases in PDE1C expression and decreases
      in the levels of both cAMP and cGMP. The increase in proliferation and migration
      was reversed by treatment with a PDE1C inhibitor, suggesting that JMJD6
      attenuates the proliferation and migration of ADSCs as an epigenetic regulator
      and PDE1C partially contributes to the JMJD6-mediated regulation. CONCLUSIONS:
      Taken together, our results indicate for the first time that JMJD6 plays an
      important role in the regulation of ADSCs proliferation and migration through the
      modulation of PDE1C expression.

PMID- 30092851
TI  - Review: Adaptation of ruminant livestock production systems to climate changes.
AB  - There is growing evidence on the extent to which projected changes in climate,
      including increases in atmospheric levels of carbon dioxide, higher temperatures,
      changes in amount, seasonality and variability of precipitation and increases in
      extreme weather events, may affect future availability of ruminant animal
      products. Elements of climate change affect livestock systems through direct
      impacts on animal physiology, behaviour, production and welfare and indirectly
      through feed availability, composition and quality. These impacts may be positive
      or negative and will vary across geographical regions, animal species and with
      adaptive capacity. However, adverse impacts are likely to be greatest in tropical
      and sub-tropical regions including countries where both current need and future
      growth in demand for nutrition is greatest. The complexity of effects means that
      effective adaptation strategies to mitigate negative impacts on ruminant
      production systems to climate changes will need to be multi-dimensional. Although
      predictions of future climate, particularly on regional and local scales, have a
      degree of uncertainty, adaptation planning is starting to be informed by changes
      already being observed and adjustments in management being made by farmers to
      maintain productivity and profitability. Regional case studies illustrate the
      benefits and limitations of adaptive management: potential mitigation through
      heightened awareness of heat stress-related mortality in French cattle; evidence
      of a drop in milk production in south-eastern Australian dairies during a January
      2014 heat wave, from the theoretical potential of 53% to only 10% across the
      state; and limitations in response options to climate-induced thermal,
      nutritional and water stress for sheep and goat farmers in northern Ethiopia.
      Review of research on climate change impacts on ruminant livestock and effective
      adaptation together with evidence of practical adaptive management provide
      insights into potential strategies and gaps in knowledge to address challenges
      and improve future decisions.

PMID- 30092852
TI  - Effects of a participatory approach, with systematic impact matrix analysis in
      herd health planning in organic dairy cattle herds.
AB  - The animal health and welfare status in European organic dairy production does
      not in all aspects meet the organic principles and consumers' expectations and
      needs to be improved. To achieve this, tailored herd health planning, targeted to
      the specific situation of individual farms could be of use. The aim of this study
      was to apply herd health planning in a structured participatory approach, with
      impact matrix analysis, not previously used in this context, in European organic
      dairy farms and to assess changes in animal health and welfare. Herd health
      planning farm visits were conducted on 122 organic dairy farms in France, Germany
      and Sweden. The farmer, the herd veterinarian and/or an advisor took part in the
      farm discussions. The researcher served as facilitator. Baseline data on the
      animal health status of the individual farm, collected from national milk
      recording schemes, were presented as an input for the discussion. Thereafter a
      systematic impact matrix analysis was performed. This was to capture the
      complexity of individual farms with the aim to identify the farm-specific factors
      that could have a strong impact on animal health. The participants (i.e. farmer,
      veterinarian and advisor) jointly identified areas in need of improvement, taking
      the health status and the interconnected farm system components into account, and
      appropriate actions were jointly identified. The researcher took minutes during
      the discussions, and these were shared with the participants. No intervention was
      made by the researcher, and further actions were left with the participants. The
      number of actions per farm ranged from 0 to 22. The change in mortality,
      metabolic diseases, reproductive performance and udder health was assessed at two
      time points, and potential determinators of the change were evaluated with linear
      regression models. A significant association was seen between change in udder
      health, as measured by the somatic cell count, and country. At the first follow
      up, a significant association was also found between change in the proportion of
      prolonged calving interval and the farmers' desire to improve reproductive health
      as well as with an increase in herd size, but this was not seen at the second
      follow-up. The degree of implementation of the actions was good (median 67%,
      lower quartile 40%, upper quartile 83%). To conclude, the degree of
      implementation was quite high, improvement of animal health could not be linked
      to the herd health planning approach. However, the approach was highly
      appreciated by the participants and deserves further study.

PMID- 30092853
TI  - Invited review: Bioinformatic methods to discover the likely causal variant of a
      new autosomal recessive genetic condition using genome-wide data.
AB  - In animals, new autosomal recessive genetic diseases (ARGD) arise all the time
      due to the regular, random mutations that occur during meiosis. In order to
      reduce the effect of any damaging new variant, it is necessary to find its cause.
      To evaluate the best way of doing this, 34 papers which found the exact location
      of a new genetic disease in livestock were reviewed and found to require at least
      two stages. In the initial stage the commonly used chi 2 method, applied in a
      case-control association analysis with single nucleotide polymorphism (SNP)-chip
      data, was found to have limitations and was almost always used in conjunction
      with a second method to locate the target region on the genome containing the
      variant. The commonly used methods had their drawbacks; so a new method was
      devised based on long runs of homozygosity, a common feature of new ARGD. This
      'autozygosity by difference' method was found to be as good as, or better than,
      all the reviewed methods tested based on its ability to unambiguously find the
      shortest known target region in an already analysed data set. Mean target region
      length was found to be 4.6 megabases in the published reports. Success did not
      depend on the size of commercial SNP-chip used, and studies with as few as three
      cases and four controls were large enough to find the target region. The final
      stage relied on either sequencing the candidate genes found in the target region
      or using whole genome sequencing (WGS) on a small number of cases. Sometimes this
      latter method was used in conjunction with WGS on a number of control animals or
      resources such as the 1000 bull genomes data. Calculations showed that, in
      cattle, less than 15 animals would be needed in order to locate the new variant
      when using WGS data. This could be any combination of cases plus parents or other
      unrelated animals in the breed. Using WGS data, it would be necessary to search
      the three billion bases of the cattle genome for base positions which were
      homozygous for the same allele in all cases and heterozygous for that allele in
      parents, or not containing that homozygote in unrelated controls. This site could
      be confirmed on other healthy animals using much cheaper methods, and then a
      genetic test could be devised for that variant in order to screen the whole
      population and to devise a breeding programme to eliminate the disorder from the
      population.

PMID- 30092854
TI  - Development and Characterization of a Model for Inducing Fetal Hemoglobin
      Production in Cynomolgus Macaques (Macaca fasicularis).
AB  - Hydroxyurea induces production of fetal hemoglobin (HbF), a tetramer of alpha and
      gamma globin proteins and corresponding heme molecules, normally found in less
      than 1% of adult RBC. Increases in circulating HbF are correlated with clinical
      improvement of patients with hemoglobinopathies, and hydroxyurea, as a daily
      medication, is the standard treatment for sickle cell anemia. Although olive
      baboons (Papio anubis) are considered a key model species for HbF induction,
      cynomolgus macaques (Macaca fasicularis) are another species that conserves the
      ability to produce HbF into maturity. In this study, moderate anemia was
      experimentally induced in cynomolgus macaques by phlebotomy, to stimulate
      accelerated erythropoiesis and HbF production. In contrast to previous studies,
      vascular access ports were implanted for phlebotomy of conscious monkeys,
      followed by fluid replacement. As total Hgb levels dropped, reticulocyte counts
      and the percentage of HbF-expressing cells increased. Once total Hgb levels
      declined to less than 8 g/dL, 2 courses of oral hydroxyurea (once daily for 5 d)
      were completed, with a 9-d interval between courses. After hydroxyurea dosing,
      the percentage of HbF-expressing cells and total HbF were increased
      significantly. In addition, a significant but transient decrease in reticulocyte
      count and a transient increase in MCV occurred, replicating the characteristic
      response of patients receiving hydroxyurea. Daily clinical observations revealed
      no serious health issues or decreases in food consumption or activity levels.
      Methods were established for assessing the patency of vascular access ports. This
      study details a new protocol for the safe and routine induction of moderate
      anemia in cynomolgus macaques and validates its use in the investigation of novel
      pharmacologic entities to induce the production of HbF.

PMID- 30092856
TI  - REVIEW ARTICLE: Stress of Strains: Inbred Mice in Liver Research.
AB  - Inbred mice are the most popular animals used for in vivo liver research. These
      mice are genetically defined, readily available, less expensive to maintain than
      larger animals, and enjoy a broad array of commercial reagents for scientific
      characterization. C57BL/6 mice are the most commonly used strain. However, other
      strains discussed including BALB/c, C3H, A/J, and FVB/N may be better suited to a
      particular disease model or line of investigation. Understanding the phenotypes
      of different inbred mouse strains facilitates informed decision-making during
      experimental design. Model systems influenced by strain-dependent phenotype
      include tissue regeneration, drug-induced liver injury (DILI; e.g.
      acetaminophen), fibrosis (e.g. carbon tetrachloride, CCl4), Fas-induced
      apoptosis, cholestasis, alcohol-induced liver disease and cirrhosis, nonalcoholic
      fatty liver disease and steatohepatitis (NAFLD/NASH), and hepatocellular
      carcinoma (HCC). Thoughtful consideration of the strengths and weaknesses of each
      inbred strain in a given model system will lead to more robust data and a clearer
      understanding of translational relevance to human liver disease.

PMID- 30092855
TI  - Evaluation of Analgesic Efficacy of Meloxicam and 2 Formulations of Buprenorphine
      after Laparotomy in Female Sprague-Dawley Rats.
AB  - Managing postoperative pain in rodents is an important part of any animal care
      and use program, and identifying an optimal analgesic plan for a surgical
      procedure is critical to providing for animal welfare. Opioids and NSAID are
      commonly used in rodents, but few studies have evaluated their efficacy in
      surgical models. The current study aimed to evaluate the therapeutic efficacy of
      clinically relevant doses of buprenorphine (2 formulations) or meloxicam used in
      combination with ketamine and xylazine anesthesia in a Sprague-Dawley rat
      ovariohysterectomy surgical model. Rats received either subcutaneous saline once
      daily for 3 d, low-dose (0.05 mg/kg SC) or high-dose (0.1 mg/kg SC) buprenorphine
      twice daily for 3 d, a single injection of sustained-release buprenorphine (1.2
      mg/kg SC), or low-dose (1 mg/kg SC) or high-dose (2 mg/kg SC) meloxicam once
      daily for 3 d. Clinical analgesic efficacy was assessed over 8 d according to
      cageside observation scoring, body weight, and behavioral testing.
      Ovariohysterectomy was associated with 2 d of postoperative pain, and all 3
      buprenorphine dosing strategies and both doses of meloxicam demonstrated varying
      amounts of analgesia. Given the results of the current study, we recommend 0.05
      mg/kg SC buprenorphine at least twice daily or a single dose of 1.2 mg/kg SC of
      sustained-release buprenorphine for rats undergoing midline laparotomy with
      ovariohysterectomy. Alternatively, meloxicam at 1 to 2 mg/kg SC once daily could
      be used for this indication.

PMID- 30092857
TI  - PCR Testing of Filter Material from IVC Lids for Microbial Monitoring of Mouse
      Colonies.
AB  - Testing sentinel animals exposed to soiled bedding from colony animals is the
      most common method used for health monitoring in rodent facilities. Although
      environmental sampling is being explored-and, in many cases, has been implemented
      as an alternative, exhaust plenum sampling is not effective for all ventilated
      rack designs. This study evaluated PCR testing of filter paper from sentinel
      cages on ventilated racks. We hypothesized that testing filter paper from cages
      containing soiled bedding would be as effective as testing sentinel mice and that
      periodic shaking of cages would generate sufficient particulate movement to
      substitute for the presence of live animals. Three cages containing soiled
      bedding were maintained in each of 8 rooms; one cage contained 2 Cr:NIH(S) mice,
      one had no mice and was shaken twice weekly, and the remaining one had no mice
      and was left undisturbed. For 3 consecutive months, a piece of filter paper from
      the undersurface of the cage lid was tested monthly for adventitial agents and
      then replaced. A second piece remained on the cage undersurface for 3 mo. Fecal
      pellets and oral and fur swabs were collected from sentinel mice at months 1 and
      3 and tested for the same agents. At month 3, serology was performed on the
      sentinel mice; feces and oral and fur swabs from colony animals were tested
      concurrently for comparison. Filter paper from cages without mice and shaken were
      at least as effective than all other methods in detecting the presence of endemic
      agents, including mouse norovirus, Helicobacter spp., Pasteurella pneumotropica,
      Entamoeba muris, and Spironucleus muris. For IVC systems where exhaust plenum
      testing is ineffective, PCR testing of IVC filter tops should be considered as an
      alternative to soiled bedding sentinels. Environmental sampling may provide
      increased reliability and reduce the number of rodents used for routine health
      surveillance.

PMID- 30092858
TI  - You pay for what you get: the true cost of tuberculosis.

PMID- 30092859
TI  - Adding up the true yield of active case finding.

PMID- 30092860
TI  - The importance of TB transmission prevention in health care settings.

PMID- 30092861
TI  - Droplets, dust and guinea pigs: an historical review of tuberculosis transmission
      research, 1878-1940.
AB  - The transmission of tuberculosis (TB) occurs mainly via inhalation of airborne
      droplet nuclei; however, the precise details of this process remain uncertain. We
      reviewed the literature from 1870 to 1940, when Mycobacterium tuberculosis was
      discovered and the concept of transmission emerged as a hallmark of the
      infectious disease. By 1940, laboratory experiments, animal studies and clinical
      observation had demonstrated that cough was central to TB transmission, and that
      guinea pigs close to patients with cough could be infected, mainly by patients
      coughing small droplets likely containing only 1-2 bacilli. A minority of
      pulmonary TB patients, usually during the early stages of the disease, with thin
      watery sputum, more successfully coughed small infectious droplets than patients
      with heavily smear-positive tenacious sputum who were often too ill and too weak
      to cough vigorously. There was ongoing debate regarding the possible importance
      of desiccated sputum particles found in surface dust. Investigation of TB
      transmission has a history of more than 130 years.

PMID- 30092862
TI  - Measuring catastrophic costs due to tuberculosis in Viet Nam.
AB  - INTRODUCTION: Progress towards ending tuberculosis (TB) in Viet Nam includes
      monitoring the costs borne by patients through periodic facility-based surveys.
      OBJECTIVE: To document the magnitude of costs incurred by TB-affected households
      and establish a baseline for the top End TB indicator in Viet Nam. METHODS: A
      national survey with retrospective data collection and projection among 735
      participants in 20 stratified clusters was conducted in 2016. Each patient was
      interviewed on costs, time loss, coping measures and asset ownership. Total costs
      were expressed as a proportion of annual household income. RESULTS: In Viet Nam,
      63% of households affected by TB or multidrug-resistant TB (MDR-TB) experienced
      costs that were >20% of their annual household income. The mean patient costs
      were respectively US$1054 and US$4302 per episode of TB and MDR-TB. The most
      significant drivers of mean costs were income loss reported and purchase of
      special foods, nutritional supplements, travel and accommodation. CONCLUSION: The
      proportion of households experiencing catastrophic total costs due to TB in Viet
      Nam is high, which poses a barrier to TB diagnosis and treatment. Based on study
      results, programme and partners need to identify key areas for policy action and
      work towards a national policy guide on intervention to reduce TB patient costs.

PMID- 30092863
TI  - Cost-utility analysis of high-dose treatment for intermediate-susceptible, dose
      dependent tuberculosis patients.
AB  - SETTING: We proposed to: 1) introduce an intermediate-susceptible, dose-dependent
      (ISDD) category for Mycobacterium tuberculosis infection; and 2) treat patients
      with M. tuberculosis infection in this category with a high dose of rifampicin
      (RMP) and isoniazid (INH). OBJECTIVE: To examine the impact of our strategy on
      quality-adjusted life-years (QALY) and costs in a low-income country with a high
      prevalence of multidrug-resistant tuberculosis (MDR-TB) (Belarus) and a high
      income, low MDR-TB prevalence country (The Netherlands). DESIGN: A Markov model
      comprising 14 health states was used to simulate treatment outcomes and costs
      accrued over 5 years for a hypothetical cohort of 10 000 patients. One-way
      sensitivity analysis, probabilistic sensitivity analysis and a scenario analysis
      were also performed. RESULTS: Our strategy was shown to be cost-effective for
      Belarus, but not for the Netherlands. At a willingness-to-pay of 50 000 euros per
      QALY, the probability of our strategy being cost-effective was 50% for the
      Netherlands and 57% for Belarus. CONCLUSION: The study shows that our strategy
      could be cost-effective and more efficacious. However, more studies are needed on
      the outcomes of using higher doses of INH and RMP.

PMID- 30092864
TI  - Performance of the QuantiFERON(r)-TB Gold In-Tube assay in tuberculin skin test
      converters: a prospective cohort study.
AB  - OBJECTIVE: To investigate diagnostic agreement of the QuantiFERON(r)-TB Gold In
      Tube (QFT-GIT) test in adult tuberculin skin test (TST) converters in a high
      tuberculosis (TB) burden setting. SETTING AND DESIGN: We performed a case-cohort
      study from 2014 to 2016 in Uganda among residents who were not infected with
      Mycobacterium tuberculosis. Participants were followed up for 1 year, when they
      were retested to determine TST conversion. All TST converters and a random sample
      of participants from baseline were offered QFT-GIT testing. RESULTS: Of 368
      enrolled participants, 61 (17%) converted their TST by 1 year. Among 61
      converters, 42 were tested using QFT-GIT, 64% of whom were QFT-GIT-positive. Of
      307 participants with a persistent negative TST, 48 were tested using QFT-GIT,
      83% of whom were QFT-negative. Overall concordance of TST and QFT-GIT was
      moderate (kappa = 0.48, 95%CI 0.30-0.66). Converters with a conversion of 15 mm
      had a higher proportion of concordant QFT-GIT results (79%) than converters with
      increments of 10-14.9 mm (52%). CONCLUSION: Concordance between TST and QFT-GIT
      was moderate among TST converters in this urban African population. These
      findings call for improved tests that more accurately measure conversion to
      tuberculous infection.

PMID- 30092865
TI  - Factors affecting tuberculosis health message recall 2 years after active case
      finding in Blantyre, Malawi.
AB  - SETTING: Urban slums, Blantyre, Malawi. OBJECTIVE: To explore tuberculosis (TB)
      community-wide active case finding (cwACF) recall and accompanying messaging 2
      years after the intervention. DESIGN: This mixed-methods study used population
      weighted random cluster sampling to select three cwACF-receiving and three non
      cwACF-receiving neighbourhoods in Blantyre. Qualitative data were collected using
      12 focus group discussions (community peer-group members) and five in-depth
      interviews (TB officers) with script guides based on the concepts of the Health
      Belief Model (HBM). Thematic analysis was used to explore transcripts employing
      deductive coding. Questionnaires completed by focus group participants were used
      to collect quantitative data, providing a 'knowledge score' evaluated through
      univariate/multivariate analysis, analysis of variance and multiple linear
      regression. RESULTS: Community peer-group participants (n = 118) retained high
      awareness and positive opinions of cwACF and recognised the relationship between
      early diagnosis and reduced transmission, considering cwACF to have prompted
      subsequent health-seeking behaviour. TB-affected individuals (personal/family:
      47.5%) had significantly higher knowledge scores than unaffected individuals (P =
      0.039), but only if resident in cwACF-receiving neighbourhoods (P = 0.005 vs. P =
      0.582), implying effect modification between exposures, albeit statistically
      under-powered (P = 0.229). CONCLUSION: Consistent with epidemiological evidence
      and HBM theory, cwACF may have a permanent impact on knowledge and behaviour,
      particularly in communities with a high prevalence of TB-affected individuals.
      Behaviour change strategies should be explicitly included in cwACF planning and
      evaluation.

PMID- 30092867
TI  - 'I didn't know so many people cared about me': support for patients who interrupt
      drug-resistant TB treatment.
AB  - SETTING: Early interventions for patients who interrupt their treatment for drug
      resistant tuberculosis (DR-TB) are rarely reported and assessed. A novel, patient
      centred intervention for patients at risk of loss to follow-up (LTFU) from DR-TB
      treatment was implemented in Khayelitsha, South Africa, in September 2013.
      OBJECTIVE: To explore the experiences and perceptions of patients, key support
      persons, health care workers (HCWs) and programme managers of a patient-centred
      model. DESIGN: This was a qualitative study consisting of 18 in-depth interviews
      with patients, key support persons, HCWs, key informants and one focus group
      discussion with HCWs, between July and September 2017. Data were coded and
      thematically analysed. RESULTS: The model was well perceived and viewed
      positively by patients, care providers and programme managers. 'Normalisation'
      and tolerance of occasional treatment interruptions, tracing, tailored management
      plans and peer support were perceived to be beneficial for retaining patients in
      care. Although the model was resource-demanding, health workers were convinced
      that it 'needs to be sustained,' and proposed solutions for its standardisation.
      CONCLUSION: An intervention based on early tracing of patients who interrupt
      treatment, peer-delivered counselling and individualised management plans by a
      multidisciplinary team was considered a beneficial and acceptable model to
      support patients at risk of LTFU from DR-TB treatment.

PMID- 30092866
TI  - Resource utilization for multidrug-resistant tuberculosis household contact
      investigations (A5300/I2003).
AB  - BACKGROUND: Current guidelines recommend evaluation of the household contacts
      (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB); however,
      implementation of this policy is challenging. OBJECTIVE: To describe the resource
      utilization and operational challenges encountered when identifying and
      characterizing adult MDR-TB index cases and their HHCs. DESIGN: Cross-sectional
      study of adult MDR-TB index cases and HHCs at 16 clinical research sites in eight
      countries. Site-level resource utilization was assessed with surveys. RESULTS:
      Between October 2015 and April 2016, 308 index cases and 1018 HHCs were enrolled.
      Of 280 index cases with sputum collected, 94 were smear-positive (34%, 95%CI 28
      39), and of 201 with chest X-rays, 87 had cavitary disease (43%, 95%CI 37-50)
      after a mean duration of treatment of 8 weeks. Staff required 512 attempts to
      evaluate the 308 households, with a median time per attempt of 4 h; 77% (95%CI 73
      80) of HHCs were at increased risk for TB: 13% were aged <5 years, 8% were
      infected with the human immunodeficiency virus, and 79% were positive on the
      tuberculin skin test/interferon-gamma release assay. One hundred and twenty-one
      previously undiagnosed TB cases were identified. Issues identified by site staff
      included the complexity of personnel and participant transportation, infection
      control, personnel safety and management of stigma. CONCLUSION: HHC
      investigations can be high yield, but are labor-intensive.

PMID- 30092868
TI  - High tuberculosis transmission rate in children with nursery exposure to
      undetected pulmonary tuberculosis.
AB  - SETTING: Nursery for newborns in Busan, Republic of Korea. OBJECTIVE: To evaluate
      tuberculosis (TB) transmission from a health care worker with active pulmonary TB
      to neonatal contacts. DESIGN: For the first investigation, infants who had been
      in the nursery 3 months before the index patient was diagnosed with pulmonary TB
      were enrolled. After a child who had stayed in the nursery 10 months before the
      diagnosis of the index patient was diagnosed with tuberculous meningitis, a
      second contact investigation was conducted. RESULTS: Respectively 315 and 1334
      children participated in the first and second investigations. The mean age of the
      contacts was 66.3 days; the rate of latent tuberculous infection (LTBI) at the
      first investigation was 42.5% (134/315). Only one infant had an abnormal chest X
      ray, and was thought to have pulmonary TB. In the second investigation, the mean
      age of the participants was 17.6 months. The proportion of children with LTBI was
      18.7% (249/1334). CONCLUSIONS: The LTBI rate in the present study was much higher
      than that estimated from other contact investigations. To minimise the risk of
      nosocomial TB transmission to neonates, screening and management of TB in health
      care workers should be strengthened.

PMID- 30092869
TI  - Burden, spectrum and outcomes of children with tuberculosis diagnosed at a
      district-level hospital in South Africa.
AB  - SETTING: The Khayelitsha subdistrict has the highest burden of reported
      tuberculosis (TB) cases in Cape Town, Western Cape Province, South Africa.
      OBJECTIVES: To characterise the TB burden, spectrum and treatment outcomes among
      children managed at a district-level hospital, the Khayelitsha District Hospital.
      DESIGN: Retrospective medical record review of all children (age <13 years)
      diagnosed with TB in January-July 2014. A lay health care worker completed daily
      surveillance and supported linkage to TB care. Symptoms and investigations at
      presentation, TB disease spectrum, referral pathways and outcomes were reported.
      RESULTS: Most children were aged ?2 years (84/99, 85%), 18/96 (19%) were infected
      with the human immunodeficiency virus, 31/91 (34%) were malnourished and 80/99
      (81%) had pulmonary TB only. The majority of the children (63/80, 79%) presented
      with cough of acute onset (<2 weeks). Only 5/36 (14%) eligible child contacts had
      documentation of receiving isoniazid preventive therapy. Twelve (13%) children
      had bacteriologically confirmed pulmonary TB. Overall, 93/97 (96%) children
      successfully continued TB care after hospital discharge. Favourable TB treatment
      outcomes were recorded in only 77 (78%) children. CONCLUSIONS: Children with TB
      managed at this district-level hospital were young, and frequently had acute
      symptoms and substantial comorbidities. Missed opportunities for TB prevention
      were identified. Linkage to care support resulted in excellent continuation of TB
      care; however, treatment outcomes could be further improved.

PMID- 30092871
TI  - Evaluation of Xpert(r) MTB/RIF assay as a diagnostic test for pulmonary
      tuberculosis in children in Myanmar.
AB  - BACKGROUND: The Xpert(r) MTB/RIF assay has been recommended for the diagnosis of
      pulmonary tuberculosis (PTB). However, there are limited data from the South-East
      Asian region. SETTING: This study was carried out at a tertiary-level children's
      hospital in Mandalay, Myanmar. OBJECTIVE: To evaluate the performance of Xpert as
      a diagnostic test for PTB in children. METHODS: A cross-sectional descriptive
      study of children with suspected PTB. Gastric lavage aspirate samples were tested
      using Xpert, solid culture and smear microscopy. The performance of Xpert, solid
      culture and smear microscopy were evaluated using the revised National Institute
      of Health classification for intrathoracic TB in children as the reference
      standard. RESULTS: TB was bacteriologically confirmed in 38 (16.5%) of 231
      children with suspected PTB. Of the 38 children with confirmed TB, 36 cases were
      identified using Xpert, 16 using solid culture and 12 using smear microscopy.
      With confirmed TB as the reference standard, the sensitivity of Xpert, solid
      culture and smear microscopy was respectively 94.7% (95%CI 80.9-99.1), 42.1%
      (95%CI 26.7-59.1) and 31.6% (95%CI 18.0-48.8). CONCLUSION: Xpert has improved the
      bacteriological confirmation of PTB among hospitalised children in Myanmar.

PMID- 30092870
TI  - Risk factors for gastric aspirate culture contamination in children evaluated for
      tuberculosis in Botswana.
AB  - SETTING: Gastric aspirate (GA) sample culture is commonly performed in children
      evaluated for tuberculosis (TB) who cannot expectorate sputum. Contamination
      limits culture yield and negatively impacts care. OBJECTIVE: To evaluate the
      proportion of and factors associated with GA contamination at a central TB
      reference laboratory in Botswana. DESIGN: This was a 5-year cross-sectional study
      of untreated children aged ?12 years evaluated for TB with the first GA sample
      registered at the National Tuberculosis Reference Laboratory. We performed
      descriptive statistics to assess the risk of contamination with patient age, sex,
      transport time and distance, culture medium, and facility type. We generated
      multivariable logistic regression models using generalized estimating equation
      extension. RESULTS: We analyzed 3642 samples. The median age was 2 years
      (interquartile range [IQR] 1-4), median transport time was 4 days (IQR 2-7), and
      64.1% of samples were from clinics or health posts. TB culture positivity was
      1.6% (60/3642), and contamination was observed in 35.6% (1298/3642). Hospital
      collection was associated with lower contamination risk (adjusted OR [aOR] 0.53,
      95%CI 0.40-0.69) and Mycobacteria Growth Indicator Tube vs. Lowenstein-Jensen
      medium with higher risk (aOR 1.88, 95%CI 1.51-2.34). CONCLUSION: In routine care
      settings, high sample contamination and low TB culture yield were observed. This
      raises questions about the collection technique and storage in lower-level
      facilities and affirms higher risk with a liquid culture medium.

PMID- 30092872
TI  - Discordance in Xpert(r) MTB/RIF assay results among low bacterial load clinical
      specimens in Bangladesh.
AB  - BACKGROUND: The Xpert(r) MTB/RIF assay detects Mycobacterium tuberculosis (MTB)
      and rifampicin (RIF) resistance. RIF-resistant (RIF-R) MTB cases detected using
      Xpert on sputum specimens at three private-sector TB screening centres in Dhaka,
      Bangladesh, were subjected to consecutive confirmatory Xpert testing, the results
      of which were MTB-positive/RIF-susceptible, MTB-positive/RIF-indeterminate or MTB
      negative. OBJECTIVE: To assess the possible causes of discordant MTB and RIF-R
      results. METHODS: Discordant confirmatory Xpert test results were subjected to
      further investigations using the GenoType(r) MTBDRplus assay, culture and rpoB
      gene sequencing. RESULTS: The confirmatory Xpert test was performed on a remnant
      or a second specimen collected from individuals with an initial RIF-R result (n =
      69); 22 (32%) results were discordant, 20 of which had an 'MTB detected-very low'
      result. Further investigations were mostly concordant with the confirmatory Xpert
      test. Average variability in paired cycle threshold (Ct) values were higher in
      'MTB detected-very low' results vs. specimens with low, medium or high detected
      MTB results (P < 0.05); discordant results were mostly observed in specimens with
      'MTB detected-very low' (20/22). CONCLUSIONS: Repeating the Xpert test and
      comparing with other available tests should be considered in case of 'MTB
      detected-very low, RIF resistance detected' results on Xpert.

PMID- 30092873
TI  - Serum antiphospholipid antibody levels as biomarkers for diagnosis of pulmonary
      tuberculosis patients.
AB  - SETTING: Salvador, Bahia, Brazil. OBJECTIVE: To evaluate the immunoglobulin (Ig)M
      and total IgG antibody response to cardiolipin (CL), phosphatidylcholine (PTC),
      phosphatidylethanolamine (PE), phosphatidylinositol (PI) and sulfatide (SL-I) as
      biosignatures that can be used to diagnose pulmonary tuberculosis (TB) and its
      applicability for monitoring the efficacy of anti-tuberculosis treatment. DESIGN:
      Serum samples from 37 adult pulmonary TB patients and 48 controls (16 healthy
      household contacts, 19 household contacts with latent tuberculous infection
      [LTBI] and 13 non-TB patients with lung disease) were screened using enzyme
      linked immunosorbent assays (ELISAs) for IgM and total IgG against phospholipids.
      RESULTS: Levels of IgM response to CL, PE and PI, and IgG response to CL, PE, PI
      and PTC were significantly higher in TB patients than in control groups. Anti-CL
      IgG had the best performance characteristics, with a sensitivity and specificity
      of respectively 86.5% and 87.2%. This IgG anti-CL ELISA test detected 86.5%
      (32/37) of the TB patients, whereas the number detected using sputum smear was
      only 65.9% (24/37). After anti-tuberculosis treatment, the median value for all
      anti-phospholipid antibodies decreased significantly compared with baseline
      values (P < 0.05). CONCLUSION: Our results suggest that the total IgG anti-CL
      level could be useful to complement conventional bacteriological tests for the
      rapid diagnosis of adult pulmonary TB.

PMID- 30092874
TI  - Evaluation of leucocytes from sputum samples of pulmonary tuberculosis patients
      using flow cytometry.
AB  - SETTING: Information about the sputum cells of pulmonary tuberculosis (PTB)
      patients is scarce. The analysis of sputum cells using optical microscopy (OM) is
      a well-established method, but it has some serious limitations. OBJECTIVE: To
      establish a new flow cytometry (FC) protocol for the leucocyte evaluation of
      sputum samples from PTB patients. DESIGN: A new FC protocol using 0.1%
      dithiothreitol and 0.5% paraformaldehyde was developed to fluidise sputum samples
      and kill Mycobacterium tuberculosis, respectively, to allow the analysis of
      sputum samples collected from TB patients. The protocol was validated by
      comparing it with OM, and the cellularity of 30 sputum samples from patients with
      PTB was evaluated. RESULTS: The comparison between leucocyte subsets analysed
      using OM and FC showed agreement. Immunophenotyping of leucocytes from sputum
      samples showed that neutrophils (95.7%) comprised the largest proportion of
      sputum cells, followed by monocytes/macrophages (2.6%) and lymphocytes (1.6%).
      Among the total T-lymphocytes (100%), 12.3% were T-helper cells, 24.1% were
      cytotoxic T-cells and 62.9% were gamma/delta T; none of the T lymphocytes had the
      CD4+/CD8+ phenotype. CONCLUSION: FC is a useful method for evaluating the
      different subtypes of leucocytes present in the sputum samples of PTB patients.

PMID- 30092875
TI  - Evaluation of line-probe assay for molecular analysis and drug susceptibility of
      extra-pulmonary tuberculosis.
AB  - SETTING: Most epidemiological studies on Mycobacterium tuberculosis focus on
      pulmonary tuberculosis (TB), whereas extra-pulmonary TB (EPTB) remains poorly
      explored. OBJECTIVE: To study the rate of resistant EPTB cases among individuals
      with suspected EPTB using a commercial line-probe assay (LPA), polymerase chain
      reaction (PCR) and reverse hybridisation test. We also examined the molecular
      profile of the EPTB isolates obtained at the Himalayan Institute of Medical
      Sciences, Dehradun, India. DESIGN: EPTB samples were collected from 249 patients
      with clinical and radiological suspicion of EPTB and subjected to automated
      liquid culture, PCR and GenoType MDRTBplus according to the manufacturers'
      instructions. RESULTS: A diagnostic yield of 15% was observed among individuals
      with suspected EPTB using MGITTM (Mycobacterium Growth Indicator Tubes), which
      increased to 38% on LPA and PCR. LPA results had 100% concordance with MGIT, with
      all culture-positive samples also being positive on LPA. However, 70.2% of LPA
      positive samples did not grow Mycobacterium tuberculosis in liquid culture. Two
      (2.1%) of the culture-negative EPTB PCR-positive samples were multidrug
      resistant, 20 (21.2%) were rifampicin-monoresistant and 12 (12.7%) isoniazid
      monoresistant on LPA. CONCLUSION: Given the paucibacillary nature of EPTB, we
      demonstrated that PCR and LPA can have a vital role in establishing TB diagnosis
      in extra-pulmonary tissues.

PMID- 30092876
TI  - Cost of point-of-care lateral flow urine lipoarabinomannan antigen testing in HIV
      positive adults in South Africa.
AB  - INTRODUCTION: The World Health Organization recommends point-of-care (POC)
      lateral flow urine lipoarabinomannan (LF-LAM) for tuberculosis (TB) diagnosis in
      selected human immunodeficiency virus (HIV) positive people. South Africa had 438
      000 new TB episodes in 2016, 58.9% of which were contributed by HIV-positive
      people. LF-LAM is being considered for scale-up in South Africa. METHODS: We
      estimated the costs of using LF-LAM in HIV-positive adults with CD4 counts ? 150
      cells/MUl enrolled in the TB Fast Track Trial in South Africa. We also estimated
      costs of POC haemoglobin (Hb), as this was used in the study algorithm. Data on
      clinic-level (10 intervention clinics) and above-clinic-level costs were
      collected. RESULTS: A total of 1307 LF-LAM tests were performed at 10 clinics
      over 24 months. The mean clinic-level costs were US$12.80 per patient for LF-LAM
      and POC Hb; LF-LAM costs were US$11.49 per patient. The mean above-clinic-level
      unit costs for LF-LAM were US$12.06 for clinic preparation, training,
      coordination and mentoring. The mean total cost of LF-LAM was US$23.55 per
      patient. CONCLUSION: At clinic level, the cost of LF-LAM was comparable to other
      TB diagnostics in South Africa. It is important to consider above-clinic-level
      costs for POC tests, as these may be required to support roll-out and ensure
      successful implementation.

PMID- 30092877
TI  - Computer-assisted chest radiography reading for tuberculosis screening in people
      living with diabetes mellitus.
AB  - BACKGROUND: Diabetes mellitus is a significant risk factor for tuberculosis (TB).
      We evaluated the performance of computer-aided detection for tuberculosis
      (CAD4TB) in people living with diabetes mellitus (PLWD) in Indonesia. METHODS:
      PLWD underwent symptom screening and chest X-ray (CXR); sputum was examined in
      those with positive symptoms and/or CXR. Digital CXRs were scored using CAD4TB
      and analysed retrospectively using clinical and microbiological diagnosis as a
      reference. The area under the receiver operator curve (AUC) of CAD4TB scores was
      determined, and an optimal threshold score established. Agreement between CAD4TB
      and the radiologist's reading was determined. RESULTS: Among 346 included PLWD,
      seven (2.0%) had microbiologically confirmed and two (0.6%) had clinically
      diagnosed TB. The highest agreement of CAD4TB with radiologist reading was
      achieved using a threshold score of 70 (kappa = 0.41, P < 0.001). The AUC for
      CAD4TB was 0.89 (95%CI 0.73-1.00). A threshold score of 65 for CAD4TB resulted in
      a sensitivity, specificity, positive predictive value and negative predictive
      value of respectively 88.9% (95%CI 51.8-99.7), 88.5% (95%CI 84.6-91.7), 17.0%
      (95%CI 7.6-30.8) and 99.6% (95%CI 98.2-100). With this threshold, 48 (13.9%)
      individuals needed microbiological examination and no microbiologically confirmed
      cases were missed. CONCLUSIONS: CAD4TB has potential as a triage tool for TB
      screening in PLWD, thereby significantly reducing the need for microbiological
      examination.

PMID- 30092878
TI  - Proteobacteria community compositions correlate with bronchiectasis severity.
AB  - BACKGROUND: Proteobacteria contributes to airway inflammation and poor clinical
      outcomes in bronchiectasis. OBJECTIVE: To compare sputum Proteobacteria
      compositions according to bronchiectasis severity. METHODS: Sputum samples
      collected from 106 patients with stable bronchiectasis and 17 healthy subjects
      were split for 16srRNA sequencing and biomarker measurement. Pairwise changes in
      Proteobacteria compositions among 22 of 106 patients during stability,
      exacerbations and convalescence were compared. Patients were stratified based on
      the Bronchiectasis Severity Index (BSI). RESULTS: Respectively 44, 34 and 28
      patients had mild, moderate and severe bronchiectasis. A higher BSI was
      associated with a greater relative abundance of Proteobacteria and lower Shannon
      Wiener diversity index, Simpson diversity index and bacterial richness. Similar
      findings applied at genera levels. Proteobacteria and Pseudomonas were the major
      phylum and genus, respectively, contributing to community similarity in moderate
      to-severe bronchiectasis. These significant correlations were not observed in
      those in whom Pseudomonas aeruginosa was not isolated. Proteobacteria abundance
      correlated with lung function, but not sputum inflammatory biomarkers in severe
      bronchiectasis. Proteobacteria compositions in severe bronchiectasis were less
      likely to change significantly during exacerbations and convalescence.
      CONCLUSION: Proteobacteria compositions (particularly culturable Pseudomonas
      abundance) were correlated with bronchiectasis severity. Proteobacteria and
      Pseudomonas contributed most to community similarity in patients with a higher
      BSI, indicating microbial targets for interventions in severe bronchiectasis.

PMID- 30092879
TI  - Under-reporting of tuberculosis in Praia, Cape Verde: study reports doubtful
      results.

PMID- 30092880
TI  - In reply.

PMID- 30092881
TI  - Cross-border tuberculosis: opportunities, challenges and change.

PMID- 30092882
TI  - An opportunity to compare the effects of BCG-Moreau and BCG-Russia in Brazil.

PMID- 30092883
TI  - Failure in TB control: why should the rapid diagnostic test bear the blame?

PMID- 30092884
TI  - Predicting Success of Oral Appliance Therapy in Treating Obstructive Sleep Apnea
      Using Drug-Induced Sleep Endoscopy.
AB  - STUDY OBJECTIVES: Oral appliance therapy (OAT) can be an effective treatment
      option for patients with obstructive sleep apnea unable to tolerate continuous
      positive airway pressure. We hypothesize that drug-induced sleep endoscopy (DISE)
      can be useful in identifying patients who will benefit from OAT. METHODS: A
      retrospective review of all patients who underwent DISE (DISE group) between
      January 2014 and June 2016 was carried out. We included patients if they received
      OAT based on recommendations made by DISE findings. A control group was designed
      by selecting a sample of patients undergoing polysomnography (PSG) with an oral
      appliance in place who had not undergone prior DISE (no DISE group). The two
      cohorts were compared to evaluate the hypothesis. RESULTS: A total of 20 patients
      fit inclusion criteria for the DISE group and 20 patients for the no DISE group.
      There was no difference between the DISE and no DISE cohorts with respect to mean
      age, sex, pre-OAT body mass index, post-OAT body mass index, or pre-OAT PSG
      characteristics including: apneahypopnea index (AHI), oxygen desaturation nadir,
      or Epworth Sleepiness Scale score. There was a significantly lower treatment AHI
      (P = .04) and increased number of patients reaching an AHI less than 5 events/h
      with OAT therapy (P = .04) in the DISE group. CONCLUSIONS: Patients showing
      increased airway dimensions at the level of the velum and/or oropharynx with a
      jaw thrust may benefit the most from OAT. The use of DISE to identify this subset
      of patients is helpful in optimizing outcomes with OAT.

PMID- 30092885
TI  - Ambulatory Versus Laboratory Polysomnography in Obstructive Sleep Apnea:
      Comparative Assessment of Quality, Clinical Efficacy, Treatment Compliance, and
      Quality of Life.
AB  - STUDY OBJECTIVES: This study has as its primary objective to evaluate the quality
      and effectiveness of type II ambulatory polysomnography (Amb-PSG) versus type I
      attended laboratory polysomnography (Lab-PSG) in diagnosing obstructive sleep
      apnea (OSA). Its secondary objective is to evaluate the clinical efficacy,
      quality of life (QoL), and treatment adherence after diagnosis. METHODS: An
      observational study of patients with OSA (n = 225) in whom diagnosis was made via
      Amb-PSG (n = 114) or Lab-PSG (n = 111). Patients' clinical data were
      retrospectively assessed (including general demographic and clinical data,
      Epworth Sleepiness Scale, blood pressure, indices from polysomnography, and
      treatment adherence. Cross-sectional assessment (patient questionnaire) was used
      to evaluate clinical efficacy indicators, comorbidities, current treatment, and
      QoL. RESULTS: Polysomnography indices were comparable between Amb-PSG and Lab-PSG
      (apnea-hypopnea index: 38.9 +/- 22.5 versus 35.8 +/- 23.1 events/h; P > .05),
      except for an elevation of total sleep time (510 +/- 54.7 versus 476.3 +/- 79.4
      minutes; P < .01) and loss of oximetry signal (9.8% versus 0.0%; P < .05). Based
      on polysomnography parameters, OSA was severe in 119 patients (52.9%), moderate
      in 88 (39.1%), and mild in 18 (8.0%). Diagnostic effect of Amb-PSG in clinical
      (body mass index, blood pressure, Epworth Sleepiness Scale) and treatment follow
      up (CPAP adherence and QoL) indicators was comparable to that of Lab-PSG.
      CONCLUSIONS: Amb-PSG showed an OSA diagnostic capacity comparable to Lab-PSG.
      Secondary analyses (diagnostic quality, clinical efficacy, treatment compliance,
      QoL) underline the value of Amb-PSG as an emerging alternative to improve
      accessibility to care.

PMID- 30092886
TI  - An Update on Dual Orexin Receptor Antagonists and Their Potential Role in
      Insomnia Therapeutics.
AB  - STUDY OBJECTIVES: Current pharmacological options for the treatment of insomnia
      insufficiently meet the needs of all insomnia patients. Approved treatments are
      not consistently effective in improving sleep onset and sleep maintenance, while
      also having complicated safety profiles. These limitations highlight the unmet
      need for additional medications and treatment strategies. Initial research
      suggests that the dual orexin receptor antagonists (DORAs) may offer an
      additional pharmaceutical option to treat insomnia in some patients. METHODS: We
      reviewed the existing literature on dual orexin receptor antagonists in PubMed
      databases using the search terms "orexin receptor antagonist," "almorexant"
      "filorexant," "lembroexant" and "suvorexant"; searches were limited to English
      language primary research articles, clinical trials, and reviews. RESULTS:
      Targeting the orexin receptor system for treatment of insomnia offers an
      additional and alternative pharmacological approach to more common gamma
      aminobutyric acid agonist sedative hypnotic treatment. Effectiveness is not well
      established in the current literature; however, the literature does suggest
      efficacy. Preclinical reports also suggest the potential for treatment in
      individuals with comorbid Alzheimer disease and insomnia. CONCLUSIONS: DORAs
      offer an additional treatment option for insomnia. More clinical trials are
      needed to robustly evaluate their safety and effectiveness in several subclasses
      of individuals with insomnia. Given the published literature, head-to-head
      comparisons to existing treatment for insomnia are warranted.

PMID- 30092887
TI  - Predictors of Obtaining Polysomnography Among Otolaryngologists Prior to
      Adenotonsillectomy for Childhood Sleep-Disordered Breathing.
AB  - STUDY OBJECTIVES: (1) To assess the predictors for obtaining polysomnography
      (PSG) in children undergoing adenotonsillectomy (AT) for sleep-disordered
      breathing, and (2) to estimate the adherence to the American Academy of
      Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline recommendations for pre
      AT PSG. METHODS: This was a retrospective cohort study of children who were seen
      in the Pediatric Otolaryngology Clinic and underwent AT for sleep-disordered
      breathing over a 13-month period at a single tertiary care children's hospital.
      Patients with and without pre-AT PSG were compared using bivariate and logistic
      regression analysis to identify predictors for PSG. Electronic medical records
      were reviewed for demographic variables, medical comorbidities, and PSG data.
      Adherence to AAO-HNS guideline recommendations was estimated by calculating the
      proportion of patients who had a PSG among those who met the recommended criteria
      for pre-AT PSG. RESULTS: Mean age was 6.6 +/- 3.6 years with 53% male. A total of
      65 of 324 children (20%) underwent PSG prior to AT. The only factor significantly
      associated with pre-AT PSG was age 1 to 3 years (odds ratio 4.5, 95% confidence
      interval [2.2, 9.0], P < .001). Among patients who met AAO-HNS criteria for pre
      AT PSG, 28 of 128 (20%) underwent PSG compared to 35 of 186 (19%) who did not
      meet criteria (odds ratio 1.0, 95% confidence interval [0.6, 1.9], P = .87).
      CONCLUSIONS: Among children who underwent AT, the only significant predictor of
      obtaining pre-AT PSG was age 1 to 3 years. The rate of adherence to the AAO-HNS
      guideline recommendations was low (20%), which represents an educational
      opportunity.

PMID- 30092888
TI  - Prevalence and Clinical Significance of Respiratory Effort-Related Arousals in
      the General Population.
AB  - STUDY OBJECTIVES: To determine the prevalence and clinical associations of
      respiratory effort-related arousals (RERA) in a general population sample.
      METHODS: A total of 2,162 participants (51.2% women, 58.5 +/- 11.0 years old,
      body mass index [BMI] 25.6 +/- 4.2 kg/m2) of a general population-based cohort
      (HypnoLaus, Switzerland) underwent full polysomnography at home. Each subject
      with a RERA index >= 5 events/h was compared with an age-, sex- and apnea
      hypopnea index (AHI)-matched control without RERA. RESULTS: A RERA index >= 5
      events/h was present in 84 participants (3.8%; 95% confidence interval: 3.2
      4.8%). In 17 participants (0.8%; 95% confidence interval: 0.5-1.3%), RERAs were
      the predominant sleep breathing disorder and only one of them complained of
      excessive daytime sleepiness. Compared to matched controls, subjects with a RERA
      index >= 5 events/h were similar in terms of BMI (26.5 +/- 3.5 versus 26.3 +/-
      4.8 kg/m2, P = .73), neck circumference (38.5 +/- 3.3 versus 37.6 +/- 3.7 cm, P =
      .10) and Epworth Sleepiness Scale score (6.7 +/- 3.7 versus 6.0 +/- 3.7, P =
      .22). Also, no differences were found for hypertension (21.4% versus 27.4%, P =
      .47), diabetes (7.1% versus 7.1%, P = 1.00), or metabolic syndrome (31.0% versus
      23.8%, P = .39). CONCLUSIONS: In a middle-aged population-based cohort, the
      prevalence of a RERA index >= 5 events/h was low (3.8%) and was not associated
      with negative clinical outcomes when using the currently recommended scoring
      criteria of the American Academy of Sleep Medicine.

PMID- 30092889
TI  - Untreated Sleep Apnea: An Analysis of Administrative Data to Identify Risk
      Factors for Early Nonadherence.
AB  - STUDY OBJECTIVES: Discontinuation of positive airway pressure (PAP) treatment for
      obstructive sleep apnea (OSA) is widely reported, but research has not adequately
      addressed nonadherence with diagnostic testing for sleep disorders and initiation
      of PAP. This study sought to identify drivers of nonadherence with diagnostic
      sleep testing and PAP treatment initiation among patients preauthorized for these
      services. METHODS: This observational cohort study used preauthorization records
      from a sleep management program and administrative medical claims from a large
      commercial health insurer. Participants included adults preauthorized for sleep
      testing and a subset in whom OSA was diagnosed and who were preauthorized for PAP
      treatment. Outcome measures were nonadherence with diagnostic sleep testing and
      PAP treatment initiation, identified as lack of a claim for a preauthorized
      service within 3 months of preauthorization of that service. Risk factors for
      nonadherence included patient demographics, prescribing factors, signs and
      symptoms of OSA, comorbidities, and prior health service utilization. RESULTS: Of
      51,749 patients preauthorized for diagnostic testing, 23.5% did not undergo
      testing. Among 19,968 patients preauthorized for PAP treatment, 11.1% did not
      initiate treatment. Testing and treatment ordered by primary care providers,
      residence outside the Midwest region, and two or fewer office visits within 6
      months before preauthorization were strong predictors of nonadherence. Apnea
      hypopnea index score < 30 events/h was also a strong predictor of nonadherence
      with treatment initiation. CONCLUSIONS: This study adds to existing knowledge
      about risk factors for nonadherence with sleep testing and treatment initiation
      following preauthorization. Health plans and providers should develop strategies
      to better engage patients with higher risk of nonadherence.

PMID- 30092890
TI  - Modifying Maternal Sleep Position in Late Pregnancy Through Positional Therapy: A
      Feasibility Study.
AB  - STUDY OBJECTIVES: To test whether a customized positional therapy device,
      PrenaBelt, would reduce time spent sleeping supine and evaluate any change in
      maternal or fetal parameters, in a group of healthy pregnant women in the third
      trimester of pregnancy. METHODS: Participants underwent an in-home, overnight
      sleep study during late pregnancy (32-38 weeks). Participants were observed over
      2 nights: 1 night when the PrenaBelt was not worn (nonintervention or control)
      and 1 night when it was (intervention). The intervention night was randomly
      allocated, and the study nights were consecutive. On the control night,
      participants were filmed using a night-capable (infrared) video camera, maternal
      sleep was measured by the Watch-PAT200, and the fetus was continuously monitored
      using the Monica AN24. On the intervention night, video, maternal, and fetal
      monitoring were repeated with the addition of the mother wearing the PrenaBelt.
      RESULTS: A total of 25 healthy pregnant women were studied. Four had missing data
      for the Watch-PAT or Monica, and eight had missing or disrupted video data. Video
      determined time in bed was not significantly different during intervention and
      control nights (P = .196, r = -.23). Median time spent supine during the
      intervention night was reduced from 48.3 minutes, to 28.5 minutes during the
      control night (P = .064, r = -.33). The difference in the proportion of time
      spent supine was significant (P = .039). There was no significant difference in
      objectively estimated sleep time (P = .651, r = -.07). Improvement was observed
      in both maternal and fetal parameters during the intervention night with an
      increase in median minimum maternal oxygen saturations (control = 91.6%,
      intervention = 92.4%, P = .006, r = -.42), fewer maternal oxygen desaturations
      (control = 7.1, intervention = 5.9, P = .095, r = -.26), and fewer fetal heart
      rate decelerations (control = 14.0, intervention = 10.4, P = .045, r = -.31)
      compared to the control night. CONCLUSIONS: Results provide preliminary evidence
      that an intervention to reduce supine sleep in late pregnancy may provide
      maternal and fetal health benefits, with minimal effect on maternal perception of
      sleep quality and objectively estimated sleep time. Further research to explore
      relationships between objectively determined maternal sleep position, maternal
      respiratory indices, and fetal well-being is warranted.

PMID- 30092891
TI  - Trans-Oral Robotic Tongue Reduction for OSA: Does Lingual Anatomy Influence the
      Surgical Outcome?
AB  - STUDY OBJECTIVES: To evaluate both the influence of the volume of the excised
      base of tongue (BOT) on the surgical outcome after robotic tongue reduction in
      patients affected by obstructive sleep apnea (OSA) and the role of the lymphatic
      or muscular predominance within the removed tissue. METHODS: Fifty-one patients
      with OSA were included in this study. All patients were treated with a robotic
      tongue base reduction. Data registered for the analysis were: age, sex,
      preoperative body mass index, preoperative and postoperative apnea-hypopnea index
      (AHI), delta AHI (preoperative AHI - postoperative AHI), total volume of the
      excised BOT, total thickness of excised BOT, isolated lymphatic thickness and
      soft tissue thickness (including muscular component) of the excised BOT, and
      lymphatic/soft tissue ratio (lymphatic thickness / soft tissue thickness).
      RESULTS: A statistically significant reduction of AHI values was seen
      postoperatively, and a success rate of 74.5% was recorded. However, no
      significant correlations between delta AHI and tongue volume in cubic
      centimeters, lymphatic/soft tissue ratio, and total thickness were found.
      CONCLUSIONS: These findings reinforce the general opinion that OSA is not only
      influenced by anatomic factors but other phenomena may play a fundamental role in
      its genesis. A deeper understanding of OSA pathogenesis is needed in order to
      tailor an individual treatment strategy that could lead to a more effective
      therapy.

PMID- 30092892
TI  - Remotely Controlled Mandibular Positioning During Drug-Induced Sleep Endoscopy
      Toward Mandibular Advancement Device Therapy: Feasibility and Protocol.
AB  - STUDY OBJECTIVES: The potential of a remotely controlled mandibular positioner
      (RCMP) during sleep studies in individual patients suffering from obstructive
      sleep apnea (OSA) for the determination of the effective target protrusive
      position (ETPP) of the mandible has been demonstrated. The research goal of this
      study was to assess the feasibility of the application of RCMP during drug
      induced sleep endoscopy (DISE) for the determination of ETPP. METHODS: Ten
      patients in whom OSA was diagnosed (50% male; age 54 +/- 9.5 years; body mass
      index 26.9 +/- 2.1 kg/m2; apnea-hypopnea index 28.4 +/- 13.2 events/h) were
      enrolled prospectively. Dental RCMP trays were fitted during wakefulness. Maximal
      protrusion and edge-to-edge positions were measured. Upper airway collapsibility
      was scored during DISE, including full-range mandibular RCMP titration within 45
      minutes. ETPP was defined as the mandibular threshold protrusion yielding a
      stable upper airway in the absence of snoring, oxygen desaturation and apneas.
      RESULTS: RCMP trays were retentive and no adverse reactions occurred. RCMP was
      fitted intraorally prior to sedation with maxillary and mandibular trays in edge
      to-edge position. Upon sedation, progressive protrusion was performed followed by
      reversed titration until ETPP was noted. In one patient ETPP was not within the
      mandibular range of motion. In one patient RCMP needed to be removed because of
      clenching. CONCLUSIONS: The results of this study illustrate that it is feasible
      to use RCMP during DISE and to determine ETPP within 45 minutes. Comparative
      research with polysomnography would be useful to further validate the therapy
      outcome upon use of RCMP during DISE.

PMID- 30092893
TI  - The Epworth Sleepiness Scale: Validation of One-Dimensional Factor Structure in a
      Large Clinical Sample.
AB  - STUDY OBJECTIVES: The Epworth Sleepiness Scale (ESS) is used by clinicians and
      researchers to determine level of daytime sleepiness. The number of factors
      included in the scale has been debated. Our study objective was to clarify the
      dimensionality of the ESS using a large clinical sample. METHODS: A retrospective
      cohort study included all patients presenting for care in a tertiary care sleep
      disorders center who answered all items on the ESS from January 8, 2008 to
      September 28, 2012. Dimensionality was assessed using scree plot, eigenvalues,
      factor loadings, principal factor analysis, and confirmatory factor analysis.
      Multigroup confirmatory factor analysis (MGCFA) evaluated dimensionality within
      10 subgroups of clinical interest. RESULTS: The mean age of the 10,785 study
      participants was 50 (+/- 15) years with 49% female, and 81% white. The one-factor
      solution explained 63% of the variability in responses with high factor loadings
      (> .67 for all 8 items). The scree plot identified one factor with eigenvalue >
      1. Results of confirmatory factor analysis demonstrated a one-factor solution had
      acceptable goodness of fit as assessed by root mean square error of approximation
      of .094 (90% confidence interval: .089-.099). MGCFA confirmed measurement
      invariance within all 10 demographic and clinical subgroups. CONCLUSIONS: Our
      study confirmed the unidimensionality of the ESS in a large diverse clinical
      population. Results from this study can be used to justify the interpretation of
      the ESS within clinical populations, and supports valid comparisons between
      groups based on the ESS. Future studies are warranted to further understand the
      items comprising the ESS and potentially eliminate redundant items for increased
      efficiency in clinical settings.

PMID- 30092894
TI  - Continuous Positive Airway Pressure Therapy on Nonalcoholic Fatty Liver Disease
      in Patients With Obstructive Sleep Apnea.
AB  - STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with nonalcoholic
      fatty liver disease (NAFLD) and related advanced fibrosis. We studied the
      treatment of OSA with continuous positive airway pressure (CPAP) in a population
      with NAFLD. METHODS: Using an institutional database (2010-2014), we identified
      patients with NAFLD and OSA and studied changes in serum aminotransferases before
      and after CPAP use. We defined suspected NAFLD (sNAFLD) as serum alanine
      aminotransferase (ALT) > 30 U/L for men and > 19 U/L for women in the absence of
      known causes of chronic liver disease. The aspartate aminotransferase (AST) to
      platelet ratio index (APRI) was used to determine significant fibrosis.
      Consistent CPAP use for more than 3 months with adequate adherence parameters
      defined good adherence. RESULTS: Of 351 patients with OSA on CPAP treatment,
      majority (mean age 57.6 years, 59.3% male) had abnormal ALT, and 89.4% met the
      criteria for sNAFLD. The prevalence of sNAFLD was higher among patients with
      moderate to severe OSA (90.6%) versus mild OSA (86.3%). There was a statistically
      significant improvement in AST, ALT, and APRI with CPAP therapy (all P < .01).
      There was an apparent dose-response relationship: patients with good adherence to
      CPAP showed a significantly larger decrease in AST and ALT than did those with
      poor adherence (P < .01). Multivariable logistic regression analysis showed CPAP
      treatment with adequate adherence (odds ratio = 3.93, 95% confidence interval =
      1.29-11.94) was an independent predictor of regression of sNAFLD after adjusting
      for obesity class and severity of OSA. CONCLUSIONS: OSA treatment with CPAP was
      associated with significant biochemical improvement and reduction in NAFLD
      related fibrosis.

PMID- 30092897
TI  - FOXP1 Syndrome and Severe Obstructive Sleep Apnea.

PMID- 30092895
TI  - Study of Associated Factors With Probable Sleep Bruxism Among Adolescents.
AB  - STUDY OBJECTIVES: To evaluate the prevalence of probable sleep bruxism (SB) and
      its association with sleep features, orthodontic fixed appliance wearing, and
      extraoral and intraoral clinical signs and symptoms in a population of
      adolescents. METHODS: Two hundred thirty-nine 12-year-old adolescents enrolled in
      private and public schools in Brumadinho, southeast Brazil, and their parents
      were invited to participate. They answered a questionnaire containing information
      regarding adolescents' sleep features and history of SB. Extraoral and intraoral
      examination was performed to identify some clinical signs (ie, absence of lip
      competence, presence of mouth breathing, clicks in the temporomandibular joint
      [TMJ], tooth wear) and symptoms (ie, pain in the masseter muscle upon palpation),
      and ongoing orthodontic treatment with fixed appliances. Parental report and
      clinical examination were used to determine probable SB. Descriptive statistics
      and logistic regression were performed to identify association of probable SB
      with independent variables. RESULTS: Of 239 adolescents initially selected, 231
      (96.6%) participated in the study. Prevalence of probable SB was 16.9%.
      Adolescents who snored during sleep (odds ratio [OR] = 3.14; 95% confidence
      interval [CI] = 1.47-6.70), adolescents who did not have clicks in the TMJ (OR =
      3.37; 95% CI = 1.11-10.15), and those who wore orthodontic appliances (OR = 2.72;
      95% CI = 1.04-7.14) were more likely to be in the group with probable SB.
      CONCLUSIONS: Snoring, absence of clicks in the TMJ, and fixed appliance wearing
      were associated with probable SB among adolescents. This study adds to the
      ongoing research on SB in adolescents and its associated factors. COMMENTARY: A
      commentary on this article appears in this issue on page 1281.

PMID- 30092896
TI  - Association Between Sleep Duration, Quality and Body Mass Index in the Korean
      Population.
AB  - STUDY OBJECTIVES: Mounting evidence indicates that sleep disturbance contributes
      to the increased risk for cardiometabolic diseases. Obesity and underweight are
      also closely linked to cardiometabolic risk. Thus, the objective of this study
      was to examine the association between sleep duration, quality, and body mass
      index (BMI) categories. METHODS: Using data from a cohort of 107,718 Korean
      individuals (63,421 men and 44,297 women), we conducted cross-sectional analysis
      with sex subgroup analysis. Sleep duration was classified into 3 groups-short (<
      7 hours), normal (7-9 hours) and long sleep (> 9 hours)-and Pittsburgh Sleep
      Quality Index (PSQI) score was used to divide sleep quality into 2 groups-poor
      (PSQI > 5) and good sleep (PSQI <= 5). Compared to normal sleep and good sleep
      quality, adjusted odds ratios of short and long sleep and poor sleep for BMI
      categories were calculated. BMI categories included underweight (BMI < 18.5
      kg/m2), overweight (BMI 23 to < 25 kg/m2), obesity (BMI 25 to < 30 kg/m2) and
      severe obesity (BMI >= 30 kg/m2). RESULTS: Short sleep duration had the dose
      dependent relationship with obesity categories from overweight to severe obesity,
      and inverse relationship with underweight (adjusted odds ratios [95% confidence
      intervals] for underweight, overweight, obesity, and severe obesity versus normal
      weight; 0.88 [0.82-0.94], 1.15 [1.11-1.20], 1.31 [1.26-1.37], 1.70 [1.54-1.85]).
      Poor sleep quality was significantly associated with severe obesity in male
      subgroup (1.16 [1.05-1.27]) and with obesity (1.18 [1.10-1.25]) and severe
      obesity in female subgroup (1.66 [1.40-1.98]). CONCLUSIONS: Short sleep duration
      and poor sleep quality was more positively associated with obesity across BMI
      than underweight.

PMID- 30092899
TI  - A Novel Treatment for Nasolacrimal Air Regurgitation Into the Eye With CPAP: The
      Total Face Mask.
AB  - ABSTRACT: We present a patient who experienced insufflation of air under the left
      eyelid when using continuous positive airway pressure (CPAP) via an oronasal
      mask. The patient had a lacrimal stent in place for many years, which was a
      predisposing factor for this complication. Lacrimal stents are frequently used in
      the treatment of epiphora (excessive tearing) secondary to obstruction of the
      lacrimal drainage system. In this case, we review the pathophysiology of air
      regurgitation into the eye with CPAP use and methods previously described to
      address this rare complication. We also present a novel intervention for this
      rare complication, the total face mask. By additionally covering the eyes, a
      total face mask allows equalization of pressure on both sides of the lacrimal
      system. With a total face mask, our patient was able to successfully use CPAP.

PMID- 30092898
TI  - Sleep Hygiene Index: Psychometric Characteristics and Usefulness as a Screening
      Tool in a Sample of Nigerian Undergraduate Students.
AB  - STUDY OBJECTIVES: The objectives of this study were to investigate the
      psychometric properties of the Sleep Hygiene Index (SHI) and determine its
      capacity to screen for poor sleep quality in a nonclinical sample of Nigerian
      university students. METHODS: A total of 348 students appropriately completed the
      SHI, the Morningness-Eveningness Questionnaire (MEQ), the Pittsburgh Sleep
      Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS). RESULTS: The
      internal consistency (Cronbach alpha) of the SHI was .64 and its construct
      validity was modestly satisfactory. It had a significant negative correlation
      with the MEQ (r = -.170, P < .001) and positive correlations with global PSQI (r
      = .289, P < .001) and ESS (r = .219, P < .001) scores. Prior to the factor
      analysis, our sample was randomly divided into two. In one half of the sample
      (sample 1), exploratory factor analysis of the SHI items yielded a three-factor
      model. Confirmatory factor analysis on the other half (sample 2) corroborated
      this model with satisfactory indices of fitness (c2 = 67.805; df = 55; c2/df =
      1.233; P = .115; goodness of fit index = .943; Tucker-Lewis index = .958;
      incremental fit index = .972; comparative fit index = .970; root mean square
      error of approximation = .037). A cutoff total score of 16 on the SHI had the
      best sensitivity (77.0%) and specificity (47.5%) to identify students who were
      categorized as experiencing poor sleep quality, according to the PSQI (area under
      the curve = 0.65, 95% confidence interval = 0.59-0.71). CONCLUSIONS: The SHI
      exhibited satisfactory psychometric properties as a self-rated assessment
      instrument in the evaluation of sleep hygiene and as a screening instrument for
      poor sleep quality among Nigerian undergraduate students.

PMID- 30092901
TI  - Case Report of Pediatric Channelopathies With UNC80 and KCNJ11 Mutations Having
      Abnormal Respiratory Control Treated With Positive Airway Pressure Therapy.
AB  - ABSTRACT: There have been no published reports of central respiratory control
      abnormalities in pediatric patients with UNC80 or KCNJ11 mutations which cause
      neurologic channelopathies. We describe an 8-year-old male with a pathogenic
      UNC80 mutation, intellectual disability, hypotonia and epilepsy with severe
      central sleep apnea (213.5 events/h) on polysomnography (PSG). We also describe a
      20-month-old female with a KCNJ11 mutation, neonatal diabetes and developmental
      delay who had severe central sleep apnea (131.1 events/h). Both patients had
      irregular respiratory patterns during sleep and wakefulness and were placed on
      empiric bilevel positive airway pressure therapy, which was well tolerated with
      resolution of abnormal respiratory control and hypercapnia. Patients with UNC80
      and KCNJ11 gene mutations may have abnormal respiratory rhythm during sleep and
      wakefulness, mirroring animal models. We recommend routine PSG tests and further
      investigation into the respiratory control of patients with pediatric
      channelopathies involved in chemoreceptor function or central integration of
      respiratory control.

PMID- 30092900
TI  - Home Polysomnography Reveals a First-Night Effect in Patients With Low Sleep
      Bruxism Activity.
AB  - STUDY OBJECTIVES: To examine the presence of a first-night effect (FNE) and the
      level of internight variability in sleep bruxism (SB) activity when a self
      applicable electrode set is used in home polysomnography (PSG) in a sample of
      subjects with possible SB. METHODS: Fourteen females and two males aged 38.3 +/-
      9.1 years (mean +/- standard deviation) with self-reported SB underwent home-PSG
      on three consecutive nights. The subjects applied PSG sensors themselves,
      including self-applicable electrode sets used to record sleep and masseter muscle
      activity. Repeated-measures analysis of variance was used to compare SB and sleep
      variables between the nights. RESULTS: Surprisingly, there were statistically
      significant elevations in the rhythmic masticatory muscle activity (RMMA) episode
      index (P = .009), burst index (P = .016), and bruxism time index (P = .049)
      throughout the course of 3 nights. More bruxers were diagnosed on the second (6
      bruxers, >= 2 episodes/h) and third night (7 bruxers) compared to the first night
      (2 bruxers). Most subjects (14/16) had their highest RMMA index on the second or
      third night. The mean coefficient of variation for RMMA episode index was 50.7%.
      No statistically significant differences were detected in other sleep variables.
      CONCLUSIONS: The results indicate that a FNE may be present in SB activity,
      possibly lasting several nights in some subjects. Furthermore, FNE appears to be
      combined with high internight variability of SB activity without indications of
      internight changes in sleep macrostructure. To confirm the level of ongoing SB
      activity, several nights of PSG may be required, especially in subjects with low
      first-night SB activity. COMMENTARY: A commentary on this article appears in this
      issue on page 1281.

PMID- 30092902
TI  - Severe Positional Central Sleep Apnea in an Asymptomatic Adult With a PHOX2B
      Frameshift Mutation.
AB  - ABSTRACT: We report an unusual case of an adult patient carrying a germline
      PHOX2B frameshift mutation and hence was diagnosed with congenital central
      hypoventilation syndrome. He came to medical attention after the mutation was
      identified in his daughter who presented with hypoventilation and a
      neuroblastoma. Although PHOX2B mutations are usually associated with a phenotype
      of congenital hypoventilation, severe autonomic dysfunction and neural crest
      tumors, our patient had no complaints at the time of presentation. At
      polysomnography we found severe positional hypercapnic central sleep apnea,
      partly responsive to positional therapy. Eventually, he was titrated to
      noninvasive ventilation with resolution of the central breathing events and, in
      hindsight, a more refreshing sleep than before. Clinicians working in sleep
      medicine need to be aware of the variable expression of this rare condition to
      prevent late cardiorespiratory and neurocognitive complications.

PMID- 30092903
TI  - A Patient With Suspicious Oxygen Desaturations at Sleep Onset.

PMID- 30092904
TI  - Discrepancy Between Oxygen Desaturation Index and Apnea-Hypopnea Index: What Do
      You Do With the Results?

PMID- 30092905
TI  - Perspective: Sleep at the USA Science and Engineering Festival-A New Outreach for
      the American Academy of Sleep Medicine.
AB  - ABSTRACT: This April, the American Academy of Sleep Medicine (AASM) took part as
      exhibitors at the USA Science and Engineering Festival in Washington, DC. This
      was AASM's first time attending the festival which is the largest conference of
      its kind promoting and celebrating science and technology in the United States
      hosting 370,000 attendees including schoolchildren, educators, and the general
      public. The AASM's exhibit featured interactive games as well as materials aimed
      at the promotion of healthy sleep habits in all age groups. A few individuals
      presented with more specific questions and were provided education and directed
      to online resources approved by the Academy. It was apparent that many people
      were unaware of the field of sleep medicine and responded favorably to our
      presence. We hope our account of the experience helps inform thought on further
      direction the AASM takes in the realm of public outreach and education.

PMID- 30092906
TI  - Prolongation of REM Sleep Latency in Nightmare Disorder May Indicate Subtle REM
      Sleep Fragmentation and Decreased REM Sleep Propensity.

PMID- 30092907
TI  - Diagnostic Accuracy and Clinical Utility of Overnight Pulse Oximetry.

PMID- 30092908
TI  - Non-24-Hour Sleep-Wake Disorder in Sighted Patients: Dealing With an Orphan
      Disease.

PMID- 30092909
TI  - Changes in REM Sleep Following Trauma Likely Significant.

PMID- 30092911
TI  - Adopting the Unentrained Orphan.

PMID- 30092910
TI  - Sleep Bruxism: A "Bridge" Between Dental and Sleep Medicine.

PMID- 30092912
TI  - Invitro culture and non-invasive metabolic profiling of single bovine embryos.
AB  - Selecting high-quality embryos for transfer has been a difficult task when
      producing bovine embryos in vitro. The most used non-invasive method is based on
      visual observation. Molecular characterisation of embryo growth media has been
      proposed as a complementary method. In this study we demonstrate a culture medium
      sampling method for identifying potential embryonic viability markers to predict
      normal or abnormal embryonic development. During single embryo culture, 20 uL
      culture media was removed at Days 2, 5 and 8 after fertilisation from the same
      droplet (60 uL). In all, 58 samples were analysed using liquid chromatography
      mass spectrometry. We demonstrate that it is possible to remove samples from the
      same culture medium droplets and not significantly affect blastocyst rate
      (25.2%). Changes in any single low molecular weight compound were not predictive
      enough. Combining multiple low molecular weight signals made it possible to
      predict Day 2 and 5 embryo development to the blastocyst stage with an accuracy
      of 64%. Elevated concentrations of lysophosphatidylethanolamines (m/z = 453, 566,
      588) in the culture media of Day 8 well-developing embryos were observed. Choline
      (104 m/z) and citrate (215 m/z) concentrations were increased in embryos in which
      development was retarded. Metabolic profiling provides possibilities to identify
      well-developing embryos before transfer, thus improving pregnancy rates and the
      number of calves born.

PMID- 30092914
TI  - Dimensional and Categorical Approaches to Understanding Attention
      Deficit/Hyperactivity Disorder: New Frontiers in Translational Research.

PMID- 30092913
TI  - Molecular characterisation of oestrogen receptor ERalpha and the effects of
      bisphenol A on its expression during sexual development in the Chinese giant
      salamander (Andrias davidianus).
AB  - The aim of this study was to characterise the molecular structure of the
      oestrogen receptor ERalpha and to evaluate the effect of bisphenol A (BPA) on
      ERalpha expression during sexual development of the Chinese giant salamander
      (Andrias davidianus). The ERalpha cDNA of A. davidianus includes an open reading
      frame of 1755 bp (encoding 584 amino acids), a 219-bp 5' untranslated region
      (UTR) and a 611-bp 3'UTR. A polyadenylation signal was not found in the 3'UTR.
      Amino acid sequence analysis showed high homology between ERalpha of A.
      davidianus and that of other amphibians, such as Andrias japonicas (99.66%
      identity) and Rana rugose (81.06% identity). In 3-year-old A. davidianus, highest
      ERalpha expression was observed in the liver and gonads. During different
      developmental stages in A. davidianus (from 1 to 3 years of age), ERalpha
      expression in the testes increased gradually. ERalpha was localised in the
      epithelial cells of seminiferous lobules and in interstitial cells. ERalpha
      positive cells were more abundant in the interstitial tissue during testicular
      development. ERalpha was located in the nucleus of oocytes during ovary
      development. We found that the sex of 6-month-old A. davidianus larvae could not
      be distinguished anatomically. The sex ratio did not change after larvae were
      treated with 10 MUM BPA for 1 month. However, BPA treatment reduced bodyweight
      and ERalpha expression in the gonads in male larvae.

PMID- 30092915
TI  - Parsing Cannabis Exposure and Predisposing Risk Effects: Does Adolescent Cannabis
      Use Cause Neurocognitive Impairment, or Result From It?

PMID- 30092918
TI  - Treatment of Peripartum Bipolar Disorder.
AB  - Bipolar disorder affects women throughout their childbearing years. During the
      perinatal period, women with bipolar disorder are vulnerable to depressive
      episode recurrences and have an increased risk for postpartum psychosis.
      Perinatal screening is critical to identify women at risk. Although medications
      are the mainstay of treatment, the choice of pharmacotherapy must be made by the
      patient based on a risk-benefit discussion with her physician. For optimal dosing
      in pregnancy, therapeutic drug monitoring may be required to maintain effective
      drug concentrations. Residual symptoms of bipolar depression are treatable with
      bright light therapy as an alternative to medication augmentation.

PMID- 30092916
TI  - Atypicality of the N170 Event-Related Potential in Autism Spectrum Disorder: A
      Meta-analysis.
AB  - BACKGROUND: Autism spectrum disorder (ASD) is associated with impaired face
      processing. The N170 event-related potential (ERP) has been considered a
      promising neural marker of this impairment. However, no quantitative review to
      date has integrated the literature to assess whether the N170 response to faces
      in individuals with ASD differs from that of typically developing (TD)
      individuals. METHODS: This meta-analysis examined the corpus of literature
      investigating difference in N170 response to faces in individuals with ASD and
      without ASD. Data from 23 studies (NASD = 374, NTD = 359) were reviewed. Meta
      analysis was used to examine the effect size of the difference in N170 latency
      and amplitude among individuals with ASD and without ASD. Analyses were also
      conducted examining hemispheric differences, potential moderators, and
      publication bias. RESULTS: On average, N170 latencies to faces were delayed in
      individuals with ASD, but amplitudes did not differ for individuals with ASD and
      TD individuals. Moderator analyses revealed that N170 amplitudes were smaller in
      magnitude in the ASD participants relative to the TD participants in adult
      samples and in those with higher cognitive ability. However, effects differed as
      a function of hemisphere of recording. No evidence of publication bias was found.
      CONCLUSIONS: Atypicality of N170-particularly latency-to faces appears to be a
      specific biomarker of social-communicative dysfunction in ASD and may relate to
      differential developmental experiences and use of compensatory cognitive
      mechanisms. Future research should examine phenotypic differences that contribute
      to N170 heterogeneity, as well as specificity of N170 differences in ASD versus
      non-ASD clinical populations, and N170 malleability with treatment.

PMID- 30092917
TI  - Functional Neuroimaging Evidence for Distinct Neurobiological Pathways in
      Attention-Deficit/Hyperactivity Disorder.
AB  - BACKGROUND: A challenge facing clinical neuroscientists is how best to synthesize
      diverse and sometimes inconsistent evidence for neuropsychological deficits and
      brain system dysfunction found in psychiatric disorders into models that guide
      etiological and treatment research. Multiple-pathway models suggest that
      psychiatric symptoms might arise from pathophysiology in different neural
      systems. This study tested dual-pathway model predictions for attention
      deficit/hyperactivity disorder (ADHD) that reward and executive function
      cognitive deficits should be related to abnormalities in corresponding
      functionally specialized neural systems. METHODS: Behavioral inhibition and
      preference for immediate rewards were assessed in N = 251 adolescent boys and
      girls ages 12 to 18 diagnosed with DSM-IV combined-subtype ADHD or non-ADHD
      control subjects. Following taxometric analyses of test performance, the
      resulting subgroups were compared on a functional magnetic resonance imaging
      monetary incentive delay task probing reward anticipation and go/no-go task of
      motor response inhibition. RESULTS: Three ADHD subgroups were identified
      consistent with different proposed pathways-ADHD with executive function/motor
      inhibition deficits, ADHD with both executive and reward deficits, and ADHD with
      relatively normal test performance. Each cognitive domain mapped to different
      ADHD brain dysfunction features as expected. However, no brain abnormalities were
      found common to all ADHD subgroups despite the fact they had nearly identical
      ADHD-related clinical characteristics. CONCLUSIONS: The results suggest that
      combined-subtype ADHD is a collection of discrete disorders for which a
      comparable behavioral end point arises through different neurobiological
      pathways. The findings raise caution about applying common cause, single-deficit
      conceptual models to individual ADHD patients and should prompt researchers to
      consider biologically defined, multifactorial etiological models for other
      psychiatric diagnoses.

PMID- 30092919
TI  - Pharmacologic Treatment of Perinatal Depression.
AB  - This review provides information about medications used to treat perinatal
      depression, including guidance around when to use certain medications and when to
      consult a mental health provider. For each group of medications, including
      selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake
      inhibitors, mirtazapine, bupropion, lithium, atypical antipsychotics, and
      lamotrigine, the risks and benefits of treatment during pregnancy and lactation
      are reviewed, and unique qualities of each medication. A treatment algorithm is
      included and a description of the Food and Drug Administration's approach to
      providing information about medications. The article also discusses hormone
      therapies and future directions for new pharmacologic treatments.

PMID- 30092920
TI  - Complementary Health Practices for Treating Perinatal Depression.
AB  - This article provides a focused review of the evidence for several complementary
      health approaches (ie, omega-3 fatty acids, folate, vitamin D, selenium, zinc,
      magnesium, B vitamins, physical activity, yoga) in the treatment of perinatal
      depression. There is evidence that some of these treatments may be reasonable to
      consider in women during pregnancy or the postpartum period. However, there are
      little data on the comparative safety and efficacy of these relative to
      traditional treatments (eg, psychotherapy, pharmacotherapy). Adequately powered
      high-quality studies are necessary to determine the role of complementary health
      practices for treating perinatal depression.

PMID- 30092922
TI  - Identification and Treatment of Peripartum Anxiety Disorders.
AB  - Anxiety disorders in the peripartum period are common and frequently overlooked.
      They can present de novo or as exacerbations of generalized anxiety disorder,
      obsessive compulsive disorder, panic disorder and social anxiety disorder, or
      posttraumatic stress disorder. Calculating a score on the Edinburgh postnatal
      depression scale is a useful method of screening for these disorders while also
      screening for perinatal depression. Treatment includes psychotherapy,
      specifically cognitive behavioral therapy, and antidepressants, the choice of
      which should be balanced between the severity of symptoms and impact of
      functioning, risks of untreated illness, and the risks associated with the use of
      medications in pregnancy and lactation. In summary, anxiety disorders in the
      peripartum period should be recognized and treated promptly.

PMID- 30092923
TI  - Perinatal Sleep Problems: Causes, Complications, and Management.
AB  - Changes in sleep are ubiquitous in the perinatal period and it is important to be
      able to determine when these changes are significant enough to indicate sleep
      deficiency associated with increased risk for poor maternal and infant outcomes.
      Guidelines for identifying sleep deficiency include insomnia symptoms,
      excessively shortened sleep duration, and perception of insufficient or
      nonrestful sleep. Causes and complicating factors related to such sleep problems
      have been well-documented and are used to tailor behavioral and pharmacologic
      treatments for women who are pregnant or in the early postpartum period.

PMID- 30092924
TI  - Management of Attention Deficit Hyperactivity Disorder During Pregnancy.
AB  - Attention deficit hyperactivity disorder (ADHD) is a common neurobehavioral
      disorder affecting 3.2% of women. More women are taking psychostimulant
      medications, including during pregnancy. Although stimulant use does not appear
      to be associated with congenital malformations, there are inconsistent data about
      other obstetric risks, and no long-term neurodevelopmental data exist to inform
      clinical management decisions. This article summarizes the available data
      regarding perinatal exposure to psychostimulants. It also highlights the
      importance of the risk-risk analysis for clinicians and patients to consider,
      weighing risks of medication exposure to risks of ADHD during pregnancy,
      including driving safety and major impairment in occupational roles.

PMID- 30092921
TI  - Recognizing and Managing Postpartum Psychosis: A Clinical Guide for Obstetric
      Providers.
AB  - Postpartum psychosis is a psychiatric emergency that affects 1 to 2 per 1000
      women. Key clinical features include mood fluctuation, abnormal thoughts or
      behaviors, and confusion. Women with a history of bipolar disorder are at
      heightened risk, as are first-time mothers; current research on the causes
      focuses on biological triggers, such as immune dysregulation. Women with
      postpartum psychosis require inpatient hospitalization and should be treated with
      lithium, antipsychotics, and benzodiazepines.

PMID- 30092925
TI  - Treatment of Perinatal Opioid Use Disorder.
AB  - Opioid agonist therapy is the standard of care for pregnant women with Opioid Use
      Disorder, but medication-assisted withdrawal from opioid agonist therapy is
      increasingly prevalent. We review available literature evaluating the risks and
      benefits of medication-assisted withdrawal. We highlight the importance of
      supporting women in making an informed treatment choice that is best for them.
      Although it is tempting to choose medication-assisted withdrawal to decrease the
      risk of newborn opioid withdrawal, we caution against this practice. Facilitating
      treatment that assists pregnant women in recovery ultimately produces the best
      outcome for women and their children.

PMID- 30092926
TI  - Impact of Pregnancy Loss on Psychological Functioning and Grief Outcomes.
AB  - This article discusses the prevalence and timing of perinatal loss. The impact
      that perinatal grief has on psychological functioning is presented, including
      common grief reactions and the risk factors for complicated grief. The ways that
      perinatal grief is processed by each parent and the impact that it has on the
      relationships is also discussed. The role of the health care professional is
      outlined and the process for them to assist grieving parents is outlined in 5
      steps. The screening process and treatment of grieving parents is also presented.

PMID- 30092927
TI  - Perinatal Intimate Partner Violence.
AB  - This article reviews the prevalence and outcomes of perinatal intimate partner
      violence (IPV). Reported rates of perinatal IPV range from 3.7% to 9.0%.
      Perinatal IPV is associated with a multitude of mental and obstetric health
      outcomes that affect the mother and child. Perinatal medical providers have an
      opportunity to detect victims of IPV and facilitate services for this population.
      Screening, safety planning, and referral procedures are essential for addressing
      this public health problem.

PMID- 30092928
TI  - The Unwelcome Guest: Working with Childhood Sexual Abuse Survivors in
      Reproductive Health Care.
AB  - Health care providers (HCPs) are often poorly prepared to respond to childhood
      sexual abuse (CSA) survivors' needs in reproductive health care. With few
      protocols addressing the CSA survivor population, HCPs struggle with delivering
      interventions that meet professional standards of care within the systemic
      constraints of reproductive health care. To bridge the gap that exists when the
      unwelcome guest of CSA enters the reproductive health care arena, it is important
      to understand the psychological influences of trauma that affect CSA survivors,
      the symptoms or behavioral cues that are commonly revealed, and therapeutic
      approaches that can facilitate positive patient-provider experiences in health
      care.

PMID- 30092929
TI  - Psychosocial Aspects of Fertility and Assisted Reproductive Technology.
AB  - Psychosocial aspects of fertility, infertility, and assisted reproductive
      technology (ART) can significantly impact patients' sense of self-identity and
      personal agency, mental well-being, sexual and marital relationships,
      reproductive efficiency, compliance with treatment, and pregnancy outcomes.
      Research is needed to understand how stress, anxiety, depression, mood disorders,
      and psychotropic medications impact fertility and infertility treatment. The
      psychosocial implications of ART on our society include a shift toward older
      maternal age at conception, the complexities of third-party reproduction, and
      consideration for the psychological and socioeconomic barriers to receiving care.
      Clinicians must understand, screen for, and identify couples struggling with the
      psychological and social aspects of fertility and ART.

PMID- 30092930
TI  - Pregnancy: An Opportune Time to Evaluate and Treat Mental Health Disorders.

PMID- 30092931
TI  - Treatment of Peripartum Mental Health Disorders: An Essential Element of Prenatal
      Care.

PMID- 30092932
TI  - Establishing an Acute Pain Service in Private Practice and Updates on Regional
      Anesthesia Billing.
AB  - Acute pain management is an expanding perioperative specialty and there is a
      renewed focus on implementing and developing an acute pain service (APS) in
      nonacademic hospitals (ie, "private practice"). An anesthesiologist-led APS can
      improve patient care by decreasing perioperative morbidity and potentially
      reducing the risk of chronic postsurgical pain syndromes. Elements of a
      successful APS include multidisciplinary collaboration to develop perioperative
      pain protocols, education of health care providers and patients, and regular
      evaluation of patient safety and quality of care metrics. Standardization of
      regional anesthesia procedures and billing practices can promote consistent
      outcomes and efficiency.

PMID- 30092933
TI  - Perioperative Considerations for the Patient with Opioid Use Disorder on
      Buprenorphine, Methadone, or Naltrexone Maintenance Therapy.
AB  - As part of a national effort to combat the current US opioid epidemic, use of
      currently Food and Drug Administration-approved drugs for the treatment of opioid
      use disorder/opioid addiction (buprenorphine, methadone, and naltrexone) is on
      the rise. To provide optimal pain control and minimize the risk of relapse and
      overdose, providers need to have an in-depth understanding of how to manage these
      medications in the perioperative setting. This article reviews key principles and
      discusses perioperative considerations for patients with opioid use disorder on
      buprenorphine, methadone, or naltrexone.

PMID- 30092934
TI  - Updates on Multimodal Analgesia for Orthopedic Surgery.
AB  - Pain control after orthopedic surgery is challenging. A multimodal approach
      provides superior analgesia with fewer side effects compared with opioids alone.
      This approach is particularly useful in light of the current opioid epidemic in
      the United States. Several new nonopioid agents have emerged into the market in
      recent years. New agents included in this review are intravenous acetaminophen,
      intranasal ketorolac, and newer nonsteroidal anti-inflammatory drugs, and the
      established medications ketamine and gabapentinoids. This article evaluates the
      evidence supporting these drugs in a multimodal context, including a brief
      discussion of cost.

PMID- 30092935
TI  - Updates in Enhanced Recovery Pathways for Total Knee Arthroplasty.
AB  - Enhanced recovery after surgery (ERAS) programs for orthopedics involve a
      multidisciplinary approach to accelerating return to function, reducing pain,
      improving patient comfort and satisfaction, reducing complications from the
      surgical procedure, reducing hospital length of stay, and reducing costs. ERAS
      pathways for patients receiving total knee arthroplasty are different from those
      having intracavitary surgery; they are less focused on fluid homeostasis and gut
      motility than they are with optimizing systemic and local analgesics and
      providing a balance between the highest quality pain control and accelerated
      return to ambulation.

PMID- 30092936
TI  - Novel Methodologies in Regional Anesthesia for Knee Arthroplasty.
AB  - Maximizing analgesia is critical following joint arthroplasty because
      postoperative pain is a major barrier to adequate physical therapy. Continuous
      peripheral nerve blocks have been the mainstay for acute pain management in this
      population; however, this and similar techniques are limited by their duration of
      action. Cryoneurolysis and peripheral nerve stimulation are two methodologies
      used for decades to treat chronic pain. With the advent of portable ultrasound
      devices and percutaneous administration equipment, both procedures may now be
      suitable for treatment of acute pain. This article reviews these two modalities
      and their application to joint arthroplasty.

PMID- 30092937
TI  - Update on Selective Regional Analgesia for Hip Surgery Patients.
AB  - In hip surgery, regional anesthesia offers benefits in pain management and
      recovery. There are a wide range of regional analgesic options; none have shown
      to be superior. Lumbar plexus block, femoral nerve block, and fascia iliaca block
      are the most supported by published literature. Other techniques, such as
      selective obturator and/or lateral femoral cutaneous nerve blocks, represent
      alternatives. Newer approaches, such as quadratus lumborum block and local
      infiltration analgesia, require rigorous studies. To realize long-term outcome
      benefits, postoperative regional analgesia must be tailored to the individual
      patient and last longer.

PMID- 30092938
TI  - Enhanced Recovery After Shoulder Arthroplasty.
AB  - Enhanced recovery after surgery (ERAS) protocols depend on multidisciplinary care
      and should be peer-reviewed and data-driven. ERAS has reduced hospital length of
      stay and complications, simultaneously improving patient outcomes. ERAS protocol
      after shoulder arthroplasty features multidisciplinary collaboration among
      different perioperative services and multimodal analgesia with a focus on
      regional anesthesia. Despite success, adoption is not universal because ERAS
      protocols are resource intensive. They require clinicians invested in the success
      of these programs and patients who can take charge of their own health. Future
      protocols need to include quality of life and functional outcome measures to
      gauge success from the patient perspective.

PMID- 30092939
TI  - Regional Anesthesia and Analgesia for Acute Trauma Patients.
AB  - Regional anesthesia for the acute trauma patient is increasing due to the growing
      appreciation of its benefits, development of newer techniques and equipment, and
      more robust training. Block procedures are expanding beyond perioperative
      interventions performed exclusively by anesthesiologists to paramedics on scene,
      emergency medicine physicians, and nurse-led services using these techniques
      early in trauma pain management. Special considerations and indications apply to
      trauma victims compared with the elective patient and must be appreciated to
      optimize safety and clinical outcomes. This review discusses current literature
      and future directions in the growing role of regional anesthesia in acute trauma
      care.

PMID- 30092940
TI  - Pediatric Ambulatory Continuous Peripheral Nerve Blocks.
AB  - Despite the widespread use of ambulatory continuous peripheral nerve blocks in
      adults, its use in children has been sporadic. Indications for the use of
      ambulatory continuous peripheral nerve block in children involve orthopedic
      procedure, where significant pain is anticipated beyond 24 hours. Techniques to
      place the perineural catheters in children are similar to that used in adults.
      The incidence of serious side effects in pediatric ambulatory continuous
      peripheral nerve block is extremely rare. When this is combined with the
      potential to increase patient and family satisfaction and decrease opioid-related
      side effects, ambulatory continuous peripheral nerve block become a compelling
      choice.

PMID- 30092941
TI  - What Can Regional Anesthesiology and Acute Pain Medicine Learn from "Big Data"?
AB  - Demonstrating value added to patients' experience through regional anesthesiology
      and acute pain medicine is critical. Evidence supporting improved outcomes can be
      derived from prospective studies or retrospective cohort studies. Population
      based studies relying on existing clinical and administrative databases are
      helpful when an outcome is rare and detecting a change would require studying
      large numbers of patients. This article discusses the effect of regional
      anesthesiology and acute pain medicine interventions on mortality and morbidity,
      infection rate, cancer recurrence, inpatient falls, local anesthetic systemic
      toxicity, persistent postsurgical pain, and health care costs.

PMID- 30092942
TI  - Regional Anesthesia: What We Need to Know in the Era of Enhanced Recovery After
      Surgery Protocols and the Opioid Epidemic.

PMID- 30092944
TI  - Environmental exposure to lead: old myths never die.

PMID- 30092943
TI  - Regional Anesthesiology and Acute Pain Medicine in the Era of Value-Based Health
      Care.

PMID- 30092945
TI  - Environmental exposure to lead: old myths never die - Authors' reply.

PMID- 30092946
TI  - Coronary Microvascular Dysfunction and Cardiovascular Risk in Obese Patients.
AB  - BACKGROUND: Besides body mass index (BMI), other discriminators of cardiovascular
      risk are needed in obese patients, who may or may not undergo consideration for
      bariatric surgery. Coronary microvascular dysfunction (CMD), defined as impaired
      coronary flow reserve (CFR) in the absence of flow-limiting coronary artery
      disease, identifies patients at risk for adverse events independently of
      traditional risk factors. OBJECTIVES: The study sought to investigate the
      relationship among obesity, CMD, and adverse outcomes. METHODS: Consecutive
      patients undergoing evaluation for coronary artery disease with cardiac stress
      positron emission tomography demonstrating normal perfusion (N = 827) were
      followed for median 5.6 years for events, including death and hospitalization for
      myocardial infarction or heart failure. RESULTS: An inverted independent J-shaped
      relationship was observed between BMI and CFR, such that in obese patients CFR
      decreased linearly with increasing BMI (adjusted p < 0.0001). In adjusted
      analyses, CFR but not BMI remained independently associated with events (for a 1
      U decrease in CFR, adjusted hazard ratio: 1.95; 95% confidence interval: 1.41 to
      2.69; p < 0.001; for a 10-U increase in BMI, adjusted hazard ratio: 1.20; 95%
      confidence interval: 0.95 to 1.50; p = 0.125) and improved model discrimination
      (C-index 0.71 to 0.74). In obese patients, individuals with impaired CFR
      demonstrated a higher adjusted rate of events (5.7% vs. 2.6%; p = 0.002), even in
      those not currently meeting indications for bariatric surgery (6.4% vs. 2.6%; p =
      0.04). CONCLUSIONS: In patients referred for testing, CMD was independently
      associated with elevated BMI and adverse outcomes, and was a better discriminator
      of risk than BMI and traditional risk factors. CFR may facilitate management of
      obese patients beyond currently used markers of risk.

PMID- 30092947
TI  - Coronary Microvascular Dysfunction: A Preferred Risk Marker in Obesity?

PMID- 30092949
TI  - Novel Markers for Adverse Events in Atrial Fibrillation.

PMID- 30092948
TI  - Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With
      Atrial Fibrillation: An ARISTOTLE Substudy.
AB  - BACKGROUND: There is little mechanistic information on factors predisposing
      atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation
      of nitric oxide (NO) might theoretically contribute to both. OBJECTIVES: The
      authors tested the hypothesis that plasma levels of the methylated arginine
      derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit
      NO generation, might be associated with outcomes in AF. METHODS: Plasma samples
      were obtained from 5,004 patients with AF at randomization to warfarin or
      apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other
      Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations
      were measured by high-performance liquid chromatography. Relationships to
      clinical characteristics were evaluated by multivariable analyses. Associations
      with major outcomes, during a median of 1.9 years follow-up, were evaluated by
      adjusted Cox proportional hazards models. RESULTS: Both ADMA and SDMA plasma
      concentrations at study entry increased significantly with patients' age, female
      sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA
      increased (p < 0.001) with both increased CHA2DS2-VASc and HAS-BLED scores, but
      decreased in the presence of diabetes. On multivariable analysis adjusting for
      established risk factors and treatment, tertile groups of ADMA concentrations
      were significantly associated with stroke/systemic embolism (p = 0.034), and
      death (p < 0.0001), whereas tertile groups of SDMA were associated with major
      bleeding and death (p < 0.001 for both). Incorporating ADMA and SDMA into CHA2DS2
      VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither
      ADMA nor SDMA predicted differential responses to warfarin or apixaban.
      CONCLUSIONS: In anticoagulated patients with AF, elevated ADMA levels are weakly
      associated with thromboembolic events, elevated SDMA levels with bleeding events
      and both are strongly associated with increased mortality. These findings suggest
      that disturbances of NO function modulate both thrombotic and hemorrhagic risk in
      anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other
      Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984).

PMID- 30092951
TI  - Percutaneous Hemodynamic Assist Devices: Unloading the Left Atrium to Prevent
      Atrial Remodeling.

PMID- 30092950
TI  - Acute Left Ventricular Unloading Reduces Atrial Stretch and Inhibits Atrial
      Arrhythmias.
AB  - BACKGROUND: Left atrium (LA) physiology is influenced by changes in left
      ventricular (LV) performance and load. OBJECTIVES: The purpose of this study was
      to define the effect of acute changes in LV loading conditions on LA physiology
      in subacute myocardial infarction (MI). METHODS: MI was percutaneously induced in
      19 Yorkshire pigs. One to 2 weeks after MI, 14 pigs underwent acute LV unloading
      using a percutaneous LV assist device, Impella. The remaining 5 pigs underwent
      acute LV loading by percutaneous induction of aortic regurgitation. A pressure
      volume catheter was inserted into the LA using a percutaneous transseptal
      approach, and LA pressure-volume loops were continuously monitored. Atrial
      arrhythmia inducibility was examined by burst-pacing of the right atrium.
      Nicotinamide adenine dinucleotide phosphate oxidase (NOX) levels and ryanodine
      receptor phosphorylation were examined in LA tissues to study the potential
      effect of stretch-dependent oxidative stress. RESULTS: MI resulted in reduced LV
      ejection fraction and increased LV end-diastolic pressure with concomitant
      increase in LA pressure and volumes. Acute LV unloading resulted in a reduction
      of LV end-diastolic pressure, which led to proportional decreases in mean LA
      pressure and maximum LA volume. LA pressure-volume loops exhibited a pump flow
      dependent, left-downward shift. This was associated with reduced LA passive
      stiffness, suggesting the alleviation of the LA stretch that was present after
      MI. Prior to acute unloading of the LV, 71% of the pigs were arrhythmia
      inducible; LV unloading reduced this to 29% (p = 0.02). Time to spontaneous
      termination of atrial arrhythmias was decreased from median 55 s (range 5 to 300
      s) to 3 s (range 0 to 59 s). In contrast, acute LV loading with aortic
      regurgitation increased LA pressure without a significant effect on
      arrhythmogenicity. Molecular analysis of LA tissue revealed that NOX2 expression
      was increased after MI, whereas acute LV unloading reduced NOX2 levels and
      diminished ryanodine receptor phosphorylation. CONCLUSIONS: Acute LV unloading
      relieves LA stretch and reduces atrial arrhythmogenicity in subacute MI.

PMID- 30092953
TI  - PCI or CABG for LMCA Revascularization in Patients With CKD: The Jury Is Still
      Out.

PMID- 30092952
TI  - Left Main Revascularization With PCI or CABG in Patients With Chronic Kidney
      Disease: EXCEL Trial.
AB  - BACKGROUND: The optimal revascularization strategy for patients with left main
      coronary artery disease (LMCAD) and chronic kidney disease (CKD) remains unclear.
      OBJECTIVES: This study investigated the comparative effectiveness of percutaneous
      coronary intervention (PCI) versus coronary artery bypass graft (CABG) surgery in
      patients with LMCAD and low or intermediate anatomical complexity according to
      baseline renal function from the multicenter randomized EXCEL (Evaluation of
      XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main
      Revascularization) trial. METHODS: CKD was defined as an estimated glomerular
      filtration rate <60 ml/min/1.73 m2 using the CKD Epidemiology Collaboration
      equation. Acute renal failure (ARF) was defined as a serum creatinine increase
      >=5.0 mg/dl from baseline or a new requirement for dialysis. The primary
      composite endpoint was the composite of death, myocardial infarction (MI), or
      stroke at 3-year follow-up. RESULTS: CKD was present in 361 of 1,869 randomized
      patients (19.3%) in whom baseline estimated glomerular filtration rate was
      available. Patients with CKD had higher 3-year rates of the primary endpoint
      compared with those without CKD (20.8% vs. 13.5%; hazard ratio [HR]: 1.60; 95%
      confidence interval [CI]: 1.22 to 2.09; p = 0.0005). ARF within 30 days occurred
      more commonly in patients with compared with those without CKD (5.0% vs. 0.8%; p
      < 0.0001), and was strongly associated with the 3-year risk of death, stroke, or
      MI (50.7% vs. 14.4%; HR: 4.59; 95% CI: 2.73 to 7.73; p < 0.0001). ARF occurred
      less commonly after revascularization with PCI compared with CABG both in
      patients with CKD (2.3% vs. 7.7%; HR: 0.28; 95% CI: 0.09 to 0.87) and in those
      without CKD (0.3% vs. 1.3%; HR: 0.20; 95% CI: 0.04 to 0.90; pinteraction = 0.71).
      There were no significant differences in the rates of the primary composite
      endpoint after PCI and CABG in patients with CKD (23.4% vs. 18.1%; HR: 1.25; 95%
      CI: 0.79 to 1.98) and without CKD (13.4% vs. 13.5%; HR: 0.97; 95% CI: 0.73 to
      1.27; pinteraction = 0.38). CONCLUSIONS: Patients with CKD undergoing
      revascularization for LMCAD in the EXCEL trial had increased rates of ARF and
      reduced event-free survival. ARF occurred less frequently after PCI compared with
      CABG. There were no significant differences between PCI and CABG in terms of
      death, stroke, or MI at 3 years in patients with and without CKD. (EXCEL Clinical
      Trial [EXCEL]; NCT01205776).

PMID- 30092955
TI  - Red Blood Cells Deserve Attention in Patients With Type 2 Diabetes.

PMID- 30092954
TI  - Erythrocytes From Patients With Type 2 Diabetes Induce Endothelial Dysfunction
      Via Arginase I.
AB  - BACKGROUND: Cardiovascular complications are major clinical problems in type 2
      diabetes mellitus (T2DM). The authors previously demonstrated a crucial role of
      red blood cells (RBCs) in control of cardiac function through arginase-dependent
      regulation of nitric oxide export from RBCs. There is alteration of RBC function,
      as well as an increase in arginase activity, in T2DM. OBJECTIVES: The authors
      hypothesized that RBCs from patients with T2DM induce endothelial dysfunction by
      up-regulation of arginase. METHODS: RBCs were isolated from patients with T2DM
      and age-matched healthy subjects and were incubated with rat aortas or human
      internal mammary arteries from nondiabetic patients for vascular reactivity and
      biochemical studies. RESULTS: Arginase activity and arginase I protein expression
      were elevated in RBCs from patients with T2DM (T2DM RBCs) through an effect
      induced by reactive oxygen species (ROS). Co-incubation of arterial segments with
      T2DM RBCs, but not RBCs from age-matched healthy subjects, significantly impaired
      endothelial function but not smooth muscle cell function in both healthy rat
      aortas and human internal mammary arteries. Endothelial dysfunction induced by
      T2DM RBCs was prevented by inhibition of arginase and ROS both at the RBC and
      vascular levels. T2DM RBCs induced increased vascular arginase I expression and
      activity through an ROS-dependent mechanism. CONCLUSIONS: This study demonstrates
      a novel mechanism behind endothelial dysfunction in T2DM that is induced by RBC
      arginase I and ROS. Targeting arginase I in RBCs may serve as a novel therapeutic
      tool for the treatment of endothelial dysfunction in T2DM.

PMID- 30092956
TI  - Clinical Diagnosis, Imaging, and Genetics of Arrhythmogenic Right Ventricular
      Cardiomyopathy/Dysplasia: JACC State-of-the-Art Review.
AB  - Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is an
      inherited cardiomyopathy that can lead to sudden cardiac death and heart failure.
      Our understanding of its pathophysiology and clinical expressivity is
      continuously evolving. The diagnosis of ARVC/D remains particularly challenging
      due to the absence of specific unique diagnostic criteria, its variable
      expressivity, and incomplete penetrance. Advances in genetics have enlarged the
      clinical spectrum of the disease, highlighting possible phenotypes that overlap
      with arrhythmogenic dilated cardiomyopathy and channelopathies. The principal
      challenges for ARVC/D diagnosis include the following: earlier detection of the
      disease, particularly in cases of focal right ventricular involvement;
      differential diagnosis from other arrhythmogenic diseases affecting the right
      ventricle; and the development of new objective electrocardiographic and imaging
      criteria for diagnosis. This review provides an update on the diagnosis of
      ARVC/D, focusing on the contribution of emerging imaging techniques, such as
      echocardiogram/magnetic resonance imaging strain measurements or computed
      tomography scanning, new electrocardiographic parameters, and high-throughput
      sequencing.

PMID- 30092958
TI  - Coronary Vasospasm-Related Sudden Cardiac Arrest in the Community.

PMID- 30092957
TI  - Telomere Length as Cardiovascular Aging Biomarker: JACC Review Topic of the Week.
AB  - Telomeres shorten with age, the major risk factor for atherosclerotic
      cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD
      patients thus suggested that critical telomere shortening may contribute to
      premature biological aging and aCVD. Therefore, telomere length often is
      suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian
      randomization studies; however, epidemiological research has shown
      disappointingly low effect sizes. It therefore remains uncertain whether telomere
      shortening is a cause of aCVD or merely a consequence. The authors argue that
      elucidating the mechanistic foundation of these findings is essential for any
      possible translation of telomere biology to the clinic. Here, they critically
      evaluate evidence for causality in animal models and human studies, and review
      popular hypotheses and discuss their clinical implications. The authors identify
      4 key questions that any successful mechanistic theory should address, and they
      discuss how atherosclerosis-associated local telomere attrition may provide the
      answers.

PMID- 30092959
TI  - Right Heart Remodeling in Olympic Athletes During 8 Years of Intensive Exercise
      Training.

PMID- 30092960
TI  - Renal Outcomes and the Relative Benefit and Harm of Intensive Treatment of
      Hypertension.

PMID- 30092961
TI  - Age, Cardiovascular Risk, and Blood Pressure Target.

PMID- 30092962
TI  - Are All Benefits and Harms Equal?

PMID- 30092963
TI  - Reply: Validation of Predicted Cardiovascular Disease Risk to Guide Intensity of
      Blood Pressure Treatment.

PMID- 30092964
TI  - Mechanistic insights into sequestration of U(VI) toward magnetic biochar: Batch,
      XPS and EXAFS techniques.
AB  - The magnetic iron oxide (Fe3O4) nanoparticles stabilized on the biochar were
      synthesized by fast pyrolysis of Fe(II)-loaded hydrophyte biomass under N2
      conditions. The batch experiments showed that magnetic biochar presented a large
      removal capacity (54.35mg/g) at pH3.0 and 293K. The reductive co-precipitation of
      U(VI) to U(IV) by magnetic biochar was demonstrated according to X-ray
      diffraction, X-ray photoelectron spectroscopy and X-ray absorption near edge
      structure analysis. According to extended X-ray absorption fine structure
      analysis, the occurrence of U-Fe and U-U shells indicated that high effective
      removal of uranium was primarily inner-sphere coordination and then reductive co
      precipitation at low pH. These observations provided the further understanding of
      uranium removal by magnetic materials in environmental remediation.

PMID- 30092966
TI  - When Left Ventricular Extracellular Volume Fraction Changes After Anthracyclines:
      Is it Due to a Change in the Numerator, Denominator, or Both?

PMID- 30092965
TI  - Anthracycline Therapy Is Associated With Cardiomyocyte Atrophy and Preclinical
      Manifestations of Heart Disease.
AB  - OBJECTIVES: The goal of this study was to demonstrate that cardiac magnetic
      resonance could reveal anthracycline-induced early tissue remodeling and its
      relation to cardiac dysfunction and left ventricular (LV) atrophy. BACKGROUND:
      Serum biomarkers of cardiac dysfunction, although elevated after chemotherapy,
      lack specificity for the mechanism of myocardial tissue alterations. METHODS: A
      total of 27 women with breast cancer (mean age 51.8 +/- 8.9 years, mean body mass
      index 26.9 +/- 3.6 kg/m2), underwent cardiac magnetic resonance before and up to
      3 times after anthracycline therapy. Cardiac magnetic resonance variables were LV
      ejection fraction, normalized T2-weighted signal intensity for myocardial edema,
      extracellular volume (ECV), LV cardiomyocyte mass, intracellular water lifetime
      (tauic; a marker of cardiomyocyte size), and late gadolinium enhancement.
      RESULTS: At baseline, patients had a relatively low (10-year) Framingham
      cardiovascular event risk (median 5%), normal LV ejection fractions (mean 69.4 +/
      3.6%), and normal LV mass index (51.4 +/- 8.0 g/m2), a mean ECV of 0.32 +/-
      0.038, mean tauic of 169 +/- 69 ms, and no late gadolinium enhancement. At 351 to
      700 days after anthracycline therapy (240 mg/m2), mean LV ejection fraction had
      declined by 12% to 58 +/- 6% (p < 0.001) and mean LV mass index by 19 g/m2 to 36
      +/- 6 g/m2 (p < 0.001), and mean ECV had increased by 0.037 to 0.36 +/- 0.04 (p =
      0.004), while mean tauic had decreased by 62 ms to 119 +/- 54 ms (p = 0.004).
      Myocardial edema peaked at about 146 to 231 days (p < 0.001). LV mass index was
      associated with tauic (beta = 4.1 +/- 1.5 g/m2 per 100-ms increase in tauic, p =
      0.007) but not with ECV. Cardiac troponin T (mean 4.6 +/- 1.4 pg/ml at baseline)
      increased significantly after anthracycline treatment (p < 0.001). Total LV
      cardiomyocyte mass, estimated as: (1 - ECV) * LV mass, declined more rapidly
      after anthracycline therapy, with peak cardiac troponin T >10 pg/ml. There was no
      evidence for any significant interaction between 10-year cardiovascular event
      risk and the effect of anthracycline therapy. CONCLUSIONS: A decrease in LV mass
      after anthracycline therapy may result from cardiomyocyte atrophy, demonstrating
      that mechanisms other than interstitial fibrosis and edema can raise ECV. The
      loss of LV cardiomyocyte mass increased with the degree of cardiomyocyte injury,
      assessed by peak cardiac troponin T after anthracycline treatment. (Doxorubicin
      Associated Cardiac Remodeling Followed by CMR in Breast Cancer Patients;
      NCT03000036).

PMID- 30092967
TI  - Cardiotoxicity and Cardiac Monitoring Among Chemotherapy-Treated Breast Cancer
      Patients.
AB  - OBJECTIVES: This study sought to determine the rate of chemotherapy-related
      cardiotoxicity and to estimate adherence to recommendations for cardiac
      monitoring among breast cancer patients treated with chemotherapy. BACKGROUND:
      Heart failure (HF) is a known complication associated with cancer therapies.
      Little is known regarding the rate of chemotherapy-related cardiotoxicity and
      adherence to recommendations for cardiac monitoring among chemotherapy-treated
      breast cancer patients. METHODS: Patients >18 years of age with a diagnosis of
      nonmetastatic invasive breast cancer between 2009 and 2014, treated with
      chemotherapy within 6 months of their diagnosis, were identified in the Truven
      Health MarketScan (IBM Watson Health, Cambridge, Massachusetts) database. HF,
      comorbidities, and treatment details were identified using diagnosis and billing
      codes. Analyses included descriptive statistics, Cox proportional hazard
      regression, and logistic regression. RESULTS: A total of 16,456 patients were
      included; the median age was 56 years old. Cardiotoxicity was identified in 4.2%
      of patients. Therapy with trastuzumab (hazard ratio [HR]: 2.01; 95% confidence
      interval [CI]: 1.72 to 2.36) and anthracyclines (HR: 1.53; 95% CI: 1.30 to 1.80),
      Deyo comorbidity scores (HR: 1.38; 95% CI: 1.15 to 1.66; HR: 2.47; 95% CI: 1.94
      to 3.15 for scores of 1 and >=2, respectively), hypertension (HR: 1.28, 95% CI:
      1.09 to 1.51), and valve disease (HR: 1.93; 95% CI: 1.48 to 2.51) were associated
      with an increased risk of cardiotoxicity. Patients <=35 years of age (HR: 0.37;
      95% CI: 0.19 to 0.72) and 36 to 49 years of age (HR: 0.49; 95% CI: 0.38 to 0.62)
      were less likely to have cardiotoxicity than patients 65 years of age and older.
      Among 4,325 patients treated with trastuzumab, guideline-adherent cardiac
      monitoring was identified in 46.2% of patients. Therapies using anthracyclines
      (odds ratio [OR]: 1.58; 95% CI: 1.35 to 1.87), taxanes (OR: 1.63; 95% CI: 1.27 to
      2.08), and radiation (OR: 1.22; 95% CI: 1.08 to 1.39) were associated with
      guideline-adherent monitoring. CONCLUSIONS: HF is an uncommon complication of
      breast cancer therapies. The risk was higher among patients treated with
      trastuzumab or anthracyclines and lower in younger patients. Cardiac monitoring
      among trastuzumab-treated patients should be a priority among high-risk patients
      and in the presence of comorbidities or other chemotherapies such as those using
      anthracyclines.

PMID- 30092968
TI  - Left Ventricular Ejection Fraction Monitoring Adherence Rates: Why So Low?

PMID- 30092969
TI  - Contemporary Role of Echocardiography for Clinical Decision Making in Patients
      During and After Cancer Therapy.
AB  - Early recognition of cancer therapy-related cardiac dysfunction (CTRCD) provides
      an opportunity to mitigate cardiac injury and risk of developing late cardiac
      events. Echocardiography serves as the cornerstone in the detection and
      surveillance of CTRCD in patients during and after cancer therapy. Guidelines
      from professional societies and regulatory agencies have been published on
      approaches to surveillance, diagnosis, and treatment of CTRCD, although adoption
      as standard of care remains limited given the lack of evidence on the prognostic
      value of asymptomatic left ventricular (LV) dysfunction in the oncology
      population. The frequency of cardiac monitoring and the appropriateness of the
      Food and Drug Administration (FDA)-recommended cardiac monitoring schedule in all
      patients receiving trastuzumab for breast cancer has been challenged.
      Interruption versus continuation of oncological therapy in the setting of
      asymptomatic LV dysfunction remains a clinical conundrum given the uncertain
      balance of the risk of cardiac dysfunction and benefit of oncology efficacy.
      Despite their limitations, echocardiographic measures of LV function continue to
      play a pivotal role in clinical decision making, with global longitudinal strain
      emerging as a promising tool in informing and facilitating the selection of
      cancer treatment and optimizing cardiovascular outcomes. This review highlights
      the key recommendations of the existing guidelines and discusses recent
      developments in cardio-oncology imaging practices with the aim of providing
      practical guidance on the role and use of echocardiography in challenging
      clinical cases in cardio-oncology.

PMID- 30092970
TI  - Radiation-Associated Cardiac Disease: A Practical Approach to Diagnosis and
      Management.
AB  - Radiation-associated cardiac disease (RACD) results in complex clinical
      presentations, unique management issues, and increased morbidity and mortality.
      Patients typically present years or even decades after radiation exposure, with
      delayed-onset cardiac damage sustained from high cumulative doses. Multimodality
      imaging is crucial to determine the manifestations and severity of disease
      because symptoms are often nonspecific. Comprehensive screening using a
      coordinated approach may enable early detection. However, timing of intervention
      should be carefully considered in these patients because surgery is often complex
      and high-risk second surgeries should be minimized in the long-term. This review
      aims to provide treating physicians with a comprehensive and clinically focused
      overview of RACD, including clinical/imaging manifestations, multi-modality
      screening recommendations, and management options.

PMID- 30092972
TI  - Multi-Modality Imaging in the Assessment of Cardiovascular Toxicity in the Cancer
      Patient.
AB  - Cancer therapy can be associated with both cardiac and vascular toxicity.
      Advanced multi-modality imaging can be used to stratify patient risk, identify
      cardiovascular injury during and after therapy, and forecast recovery.
      Echocardiography continues to be the mainstay in the evaluation of cardiac
      toxicity. Particularly, echocardiography-based strain imaging is useful for risk
      stratification of patients at baseline, and detection of subclinical left
      ventricle (LV) dysfunction during therapy. Cardiac magnetic resonance (CMR)
      serves a complementary role in the patient with poor echocardiographic or
      equilibrium radionuclide angiographic image quality or in situations where a more
      accurate and precise LV ejection fraction measurement is needed to inform
      decisions regarding discontinuation of chemotherapy. New CMR techniques like T1
      and T2 mapping and positron emission tomography (PET) imaging will help us better
      understand the structural, pathological, and metabolic myocardial changes
      associated with ventricular dysfunction or release of serum biomarkers. CMR may
      also be helpful in the evaluation of vascular complications of cancer therapy.
      Stress echocardiography, stress CMR, computed tomography, and PET are excellent
      imaging options in the evaluation of ischemia in patients receiving therapies
      that could potentially cause vasospasm or accelerated atherosclerosis.

PMID- 30092974
TI  - Research to Practice: Assessment of Left Ventricular Global Longitudinal Strain
      for Surveillance of Cancer Chemotherapeutic-Related Cardiac Dysfunction.

PMID- 30092973
TI  - In Search of a Less Invasive Approach to Cardiac Tumor Diagnosis: Multimodality
      Imaging Assessment and Biopsy.

PMID- 30092975
TI  - Pertuzumab/Trastuzumab Breast Cancer Therapy Is Associated With Complex
      Hemodynamic Abnormalities.

PMID- 30092976
TI  - Do We Need Independent Data Monitoring Boards and Adaptive Designs for Papers
      About Methodology of Strain Measurement?

PMID- 30092971
TI  - Cardiovascular Magnetic Resonance in the Oncology Patient.
AB  - Patients with or receiving potentially cardiotoxic treatment for cancer are
      susceptible to developing decrements in left ventricular mass, diastolic
      function, or systolic function. They may also experience valvular heart disease,
      pericardial disease, or intracardiac masses. Cardiovascular magnetic resonance
      may be used to assess cardiac anatomy, structure, and function and to
      characterize myocardial tissue. This combination of features facilitates the
      diagnosis and management of disease processes in patients with or those who have
      survived cancer. This report outlines and describes prior research involving
      cardiovascular magnetic resonance for assessing cardiovascular disease in
      patients with or previously having received treatment for cancer.

PMID- 30092977
TI  - Imaging in Cardio-Oncology: Where Are We and Where Should We Be Going?

PMID- 30092978
TI  - Fabrication of mechanically tough and self-recoverable nanocomposite hydrogels
      from polyacrylamide grafted cellulose nanocrystal and poly(acrylic acid).
AB  - We present a facile strategy for the fabrication of mechanically tough and self
      recoverable nanocomposite hydrogels reinforced by surface-modified cellulose
      nanocrystals. Polyacrylamide grafted cellulose nanocrystal (CNC-g-PAM) was first
      synthesized by ceric salt initiated surface graft polymerization of acrylamide
      onto CNC, then incorporated into chemically crosslinked poly(acrylic acid) (PAA)
      networks to obtain dual-crosslinked CNC-g-PAM/PAA nanocomposite hydrogels. CNC-g
      PAM acted as both interfacial compatible nanofillers and physical crosslinkers
      through reversible hydrogen bonds between PAA and PAM on the surface of CNC. FTIR
      analysis confirmed the formation of above hydrogen bonds. Scanning electron
      microscopy observations revealed good interfacial compatibility between CNC and
      PAA matrix. The nanocomposite hydrogels exhibited decreasing swelling ratio with
      increasing CNC-g-PAM content. Uniaxial tensile tests and tensile loading
      unloading tests showed that elastic modulus, breaking strength and elongation at
      break of the nanocomposite hydrogels were significantly increased compared to PAA
      hydrogel, and that the nanocomposite hydrogels exhibited good self-recovery
      ability after large deformation.

PMID- 30092979
TI  - Comparison of different extraction methods for polysaccharides from Dendrobium
      officinale stem.
AB  - The purpose of this study was to screen the optimum extraction of polysaccharides
      (DOP) from Dendrobium officinale stem. Firstly, different methods, including hot
      water extraction (HWE), cold-pressing (CP), freeze-thawing cold-pressing (FTCP),
      ultrasonic-assisted hot water extraction (UHWE), microwave-assisted hot water
      extraction (MHWE) and enzyme-assisted hot water extraction (EHWE), were employed
      to extract DOP under their respective best parameters. Then, the extraction
      yield, structure and antioxidant activity of the polysaccharides from different
      extraction methods were compared under the same condition. The data implied that
      UHWE and FTCP possessed higher extraction yield than the other extraction
      methods. Besides, DOPCP and DOPFTCP had higher molecular weight than the other
      polysaccharide samples. More importantly, DOPFTCP had the highest antioxidant
      activity. Overall, DOPFTCP exhibit high extraction yield, well-preserved
      molecular chains and best antioxidant activity, all these indicated FTCP was the
      most suitable method to extract DOP.

PMID- 30092980
TI  - Multistage extraction and purification of waste Sargassum natans to produce
      sodium alginate: An optimization approach.
AB  - Sargassum in the Caribbean region has affected the livelihood of several coastal
      communities due to the influx of large quantities of the seaweed in recent times.
      This article seeks to explore how waste Sargassum natans can be utilized to
      produce sodium alginate. The novelty in this research lies in the optimization
      process, whereby multistage extraction and precipitation were investigated over
      commonly used single stage processing, in an effort to maximize both yield and
      purity. The results showed that a maximum yield of 19% was observed after 1
      stage, while the purity was 74% after 4 stages. In addition, optimization of the
      multistage precipitation process using the Global Optimization Toolbox in MATLAB
      R2017b provided a novel model which indicated that a compromise between the
      maximum purity and yield can be obtained at 3 stages; 71-74% and 12-16%
      respectively. Furthermore, characterization was done using FTIR and NMR, with
      results comparable to a commercial sodium alginate brand, giving absorption bands
      at 1610 cm-1 and 1395 cm-1 and an M/G ratio of 0.51 respectively.

PMID- 30092981
TI  - Grafting of N-vinyl-2-pyrrolidone onto kappa-carrageenan for silver nanoparticles
      synthesis.
AB  - A water soluble, non-gel, poly (N-vinyl-2-pyrrolidone)/kappa-carrageenan (PVP/KC)
      hybrid was synthesized by graft copolymerization of N-vinylpyrrolidone (VP) onto
      kappa-carrageenan in an aqueous medium using ammonium persulphate (APS) as an
      initiator. Factors affecting the polymerization reaction such as ammonium
      persulfate concentration, reaction temperature and time, liquor to KC ratio (LR)
      and KC to VP molar ratio were studied. The results obtained revealed that the
      optimum reaction polymerization conditions to prepare that hybrid with a total
      conversion of 93.9% are: [VP], 0.1799 mol/L; VP/KC molar ratio, 50%; [APS],
      0.0105 mol/l; LR, 15 l/k; reaction temperature, 90  degrees C and reaction time,
      75 min. Moreover, the grafted KC of that hybrid was characterized via
      investigating its FTIR analysis. Furthermore, the potential application of such
      hybrid as a route for synthesis of silver nanoparticles (Ag NPs) using AgNO3 as a
      precursor was investigated. The synthesized Ag NPs are characterized using the
      ultraviolet-visible spectroscopy (UV-vis) as well as transmission electron
      microscope (TEM). The UV-vis showed a band at 435 nm that confirms the presence
      of Ag NPs. The TEM image shows that such nanoparticles have a spherical structure
      with an average size ranging from 3 -18 nm.

PMID- 30092982
TI  - Hydrogels for biomedical applications from glycol chitosan and PEG diglycidyl
      ether exhibit pro-angiogenic and antibacterial activity.
AB  - We aimed at producing a hydrogel from a chitosan (CS) derivative soluble in
      physiological conditions to avoid any purification step thus allowing to use the
      materials also as an in-situ forming material. So, we crosslinked glycol chitosan
      (GCS) with poly(ethylene glycol) diglycidyl ether (PEGDE) in water at 37  degrees
      C. The scaffolds, referred as GCS-PEG, were specifically designed to be used as
      wound dressing materials as such (after crosslinking) or as in-situ forming
      materials. Different amounts of PEGDE were tested. The obtained scaffolds showed
      macroscopic pores and a tailorable swelling in water by controlling the
      crosslinking degree. Moreover, GCS-PEG scaffolds displayed a significant
      antimicrobial activity against Staphylococcus aureus. In-vivo study using the
      chick embryo choriallantoic membrane resulted in a highly pronounced pro
      angiogenic activity suggesting important tissue regeneration properties.
      Moreover, the employed materials are commercially available, no organic solvents
      are required and the scaling up is quite predictable.

PMID- 30092983
TI  - Cellulose acetate electrospun nanofibers for drug delivery systems: Applications
      and recent advances.
AB  - Electrospinning process of nanofibers specially derivatives of cellulose presents
      high behest for developing several kinds of novel drug delivery systems (DDSs)
      due to their specific characteristics, the simplicity, beneficial and impressive
      top-down fabricating procedure. Moreover, the novel techniques of therapeutic
      agents for entrapment into core-shell nanofibers including single, coaxial and
      triaxial applied for DDSs. Recently, biodegradable polymers including derivatives
      of cellulose, hybrid materials, artificial and natural polymers have been
      remarkably considered. The acetate ester of cellulose (cellulose acetate (CA)),
      has been widely used due to biodegradability, chemical persistence,
      biocompatibility, and thermal constancy for DDSs. This article submits an
      overview of CA electrospinning techniques, applications, and its usage as a
      carrier for therapeutic agents in DDSs. Furthermore, in this study, we aimed to
      summarize the classification of therapeutic agents comprising antimicrobial
      agents incorporated CA fibers, antibacterial nanoparticles incorporated CA
      fibers, antioxidant agents loaded CA nanofibers, systematic and anti-inflammatory
      agents containing CA nanofibers. Our study has been concluded that CA electrospun
      nanofibers could be potentially applied as biocompatible and biodegradable for
      DDSs specifically in purpose-designed transdermal or wound dressing patches.

PMID- 30092985
TI  - Gas chromatography-mass spectrometry-based trimethylsilyl-alditol derivatives for
      quantitation and fingerprint analysis of Anemarrhena asphodeloides Bunge
      polysaccharides.
AB  - Here we report a novel approach using gas chromatography mass spectrometry (GCMS)
      based trimethylsilyl-alditol (TMSA) derivatives for simultaneous baseline
      separation and detection of 8 neutral saccharides and 2 uronic acids within 25
      min. Using mild alkaline conditions to dissolve the sample in advance
      significantly increased both the detection sensitivity and sample stability of
      uronic acids because of occurrence of de-lactonization, whereas no obvious
      effects were observed for neutral saccharides. Sodium borohydride reduction of
      the carbonyl group of aldoses and the subsequent formation of TMSA derivatives
      simplifies GCMS chromatograms by producing a single peak for each derivatized
      sugar. The effects of both reaction temperatures and solvent ratios between HMDS
      and TMCS on formations of TMSA derivatives were also investigated. The
      established GCMS method was successfully applied for quantitation and fingerprint
      analysis of polysaccharides from the plant Anemarrhena asphodeloides Bunge. A
      comparative analysis of A. asphodeloides polysaccharides was further performed
      between TMSA and other four types of derivatizations. The results showed that
      GCMS analysis based on precolumn TMSA derivatization coupled with fingerprint
      analysis is a comprehensive and effective technique for qualitative and
      quantitative analysis of plant polysaccharides from traditional Chinese
      medicines.

PMID- 30092984
TI  - TPGS-functionalized and ortho ester-crosslinked dextran nanogels for enhanced
      cytotoxicity on multidrug resistant tumor cells.
AB  - Herein pH-sensitive nanogels (NG1) and P-glycoprotein-repressive nanogels (NG2)
      were prepared by copolymerization between an ortho ester crosslinker (OEAM) and
      tocopheryl polyethylene glycol succinate (TPGS)-free or conjugated dextran.
      Nanogels with or without TPGS possessed a uniform diameter (~180 nm) and
      excellent stability in various physiological environments. Doxorubicin (DOX) was
      successfully loaded into NG1 and NG2 to give NG1/DOX and NG2/DOX, both of them
      showed appropriate drug release profiles under mildly acidic conditions (pH 5.0).
      NG2/DOX possessed higher drug enrichment and lethality than NG1/DOX did on MCF
      7/ADR cells. Analysis of corresponding index of efflux activity showed that NG2
      could induce depolarization of mitochondrial membrane and interfere with ATP
      metabolism. NG2/DOX also displayed increased penetration and growth inhibition on
      MCF-7/ADR multicellular spheroids. These results demonstrated that pH-sensitive
      TPGS-functionalized nanogels (NG2) as drug carriers had great potential to
      suppress drug efflux in MCF-7/ADR cells and even overcome MDR on cancer cells.

PMID- 30092986
TI  - Chitosan-sodium alginate multilayer membrane developed by Fe0@WO3 nanoparticles:
      Photocatalytic removal of hexavalent chromium.
AB  - The WO3 nanostructures were modified by doping with iron and then the
      polyethersulfone (PES) ultrafiltration (UF) membrane was developed using prepared
      Fe0-doped WO3 photocatalytic nanoparticles via layer by layer technology.
      According to UV-vis diffuse reflectance spectroscopy (UV-vis/DRS)
      characterization, the photocatalytic activity of WO3 nanoparticles could be
      improved by doping with Fe impurity. The prepared membranes were characterized by
      X-ray diffraction (XRD), atomic force microscopy (AFM), field emission scanning
      electron microscopy (FESEM), energy dispersive X-ray spectroscopy (EDX) and
      contact angle analyzer. The novel photocatalytic membranes were used in removal
      of hexavalent chromium (Cr(VI)) ions in batch mode as well as filtration system.
      The novel photocatalytic membranes have shown significant Cr(VI) ions removal
      under visible-light illumination. By depositing the (CHI-ALG)3.5 bilayers on the
      PES/UF membrane surface, the Cr(VI) rejection for 5, 25 and 50 mg/l feed
      concentration were enhanced from 21%, 17% and 9% for neat PES to 56.3%, 41.6% and
      30.1% for PES/ (CHI-ALG)3.5 membrane and 99.2%, 92.1% and 78.1% for PES/ (CHI
      ALG)3.5/ Fe0@WO3 membrane, respectively.

PMID- 30092987
TI  - Obtention of 74:26 polyester/cellulose fabric blend with super-hydrophobic and
      super-hydrophilic properties by air corona discharge treatment and their
      characterization.
AB  - A facile method was used to create both of the super-hydrophilic and super
      hydrophobic properties on polyester/cellulose fabric blend. The fabric was
      exposed to air corona discharge treatment without any extra chemical
      modification. The static contact angle of 0 degrees  and 167 degrees  was
      indicated for super-hydrophilic and super-hydrophobic samples, respectively. The
      decrease of intensity of active functional groups and the increase of roughness
      with a nano-scale pattern presented a super-hydrophobic surface that confirmed by
      ATR-FTIR, AFM and FESEM analysis. This is while the increase of intensity of the
      active functional groups and the surface roughness with a micro-scale pattern was
      shown for the super-hydrophilic sample. The wettability tests show the
      enhancement of hydrophobic and hydrophilic properties for 300 W-10 min and 800 W
      10 min corona discharge treated samples, respectively. Therefore, there is a
      critical point of the corona discharge process that enables it to create
      hydrophobic and/or hydrophilic properties on the substrates.

PMID- 30092989
TI  - Dialdehyde cellulose crosslinked poly(vinyl alcohol) hydrogels: Influence of
      catalyst and crosslinker shelf life.
AB  - Dialdehyde cellulose (DAC) derived from alpha-cellulose by periodate oxidation
      was solubilized and utilized as a suitable crosslinking agent for poly(vinyl
      alcohol) (PVA). The crosslinking occurs between reactive aldehyde groups of DAC
      on the C2 and C3 carbons of anhydroglucose unit and hydroxyl groups on PVA
      backbone in the presence of acidic catalyst. Two catalyst systems based on
      diluted hydrochloric or sulfuric acid were tested. Their influence on the PVA/DAC
      network has been investigated by solid-state 13C NMR, XRD analysis and in the
      terms of network parameters and mechanical properties. Because DAC undergoes
      structural changes and decays with time, the role of DAC solution age (1, 14 and
      28 days old) on material properties of formed PVA/DAC samples was studied as
      well. Outlined, even after 28 days after solution preparation, DAC exhibited the
      capability to act as an efficient crosslinker for PVA. The resulting material
      properties of PVA/DAC hydrogels were found to be dependent on the molecular
      weight of solubilized DAC closely related to its age and the choice of catalyst
      system. Furthermore, the DAC potential for PVA crosslinking was investigated in a
      broad concentration range. Besides, the DAC crosslinking efficiency was also
      compared to that of common crosslinking agent glutaraldehyde. The results showed
      different network topology of prepared hydrogels and exceptional crosslinking
      potential of DAC in comparison to glutaraldehyde, which is most likely related to
      DAC macromolecular character.

PMID- 30092988
TI  - Pectin based finishing to mitigate the impact of microplastics released by
      polyamide fabrics.
AB  - Washing processes of synthetic clothes have been identified as the main source of
      microplastic pollution in marine ecosystems. Textile microfibres have been found
      in marine sediments and organisms, posing a real threat for the environment. The
      development of mitigation approaches is strongly needed to prevent the impact of
      microplastics. In this work, an innovative finishing treatment of polyamide
      fabrics is proposed to mitigate the microplastic impact, by preventing the damage
      of fabrics during washings. The treatment is based on the use of pectin, a
      natural polysaccharide present in the cell walls of plants. To functionalize the
      fabric, pectin was firstly modified with glycidyl methacrylate (GMA) and then
      grafted on polyamide. Washing tests of treated fabrics showed the effectiveness
      of the treatment in reducing of about 90% the amount of microfibres released by
      untreated fabrics. Post-wash analysis of the treated fabrics revealed a promising
      resistance to the washing process.

PMID- 30092990
TI  - Enhancing bacterial cellulose production via adding mesoporous halloysite
      nanotubes in the culture medium.
AB  - Although bacterial cellulose (BC) is a fascinating, highly pure cellulose
      material for various downstream applications, production has been challenged by
      its low productivity. This work reported a facile route to significantly enhance
      BC yield without compromising its structural advantages via adding mesoporous
      halloysite nanotubes (HNTs) in the culture medium at static cultivations. The BC
      productivity of Gluconacetobacter xylinus was increased from 2.2 to 5.9 g L-1
      after 15 days of cultivation when 2 wt% of HNTs was added into the standard
      fructose medium. It appeared that the dual functionality of cell immobilization
      and oxygen release of the HNTs were responsible for enhancing the BC
      productivity. Moreover, the HNTs-resulted BC pellicle exhibited negligible
      content of HNTs contamination (~2 wt%), higher degree of crystallinity (87.7%)
      and porosity (assessed by water holding capacity, 12.7 g g-1), and showed
      promising applications especially in the bio-adsorption field.

PMID- 30092991
TI  - Characterization and biological activity of PVA hydrogel containing
      chitooligosaccharides conjugated with gallic acid.
AB  - Propionibacterium acnes plays a key role in the onset of inflammation leading to
      acne and in downregulation of the defense system against oxidative stress.
      Therefore, antibiotics such as macrolides, tetracyclines, azelaic acid, and
      erythromycin are used to reduce microbial proliferation and resulting
      inflammation. Nonetheless, antibiotic treatment has side effects including
      cytotoxicity, allergy, and diarrhea. Therefore, recent studies were focused on
      the development of alternative antimicrobial materials. We conjugated
      chitooligosaccharide (COS) with gallic acid (GA) by the hydrogen peroxide
      mediated method and evaluated antioxidant and antimicrobial activities. Then, we
      fabricated a polyvinyl alcohol (PVA) hydrogel containing COS conjugated with GA
      (GA-COS) for acne treatment. GA-COS at 5-10 kDa showed an excellent antioxidant
      activity and a better antimicrobial activity against P. acnes as compared with
      COS. In addition, the PVA hydrogel with GA-COS inhibited intracellular formation
      of reactive oxygen species and exerted antimicrobial action better than controls
      did.

PMID- 30092992
TI  - Gold nanoparticles decorated graphene oxide/nanocellulose paper for NIR laser
      induced photothermal ablation of pathogenic bacteria.
AB  - A functionalized paper based on gold nanoparticles (Au NPs) conjugated graphene
      oxide (GO) was developed for near-infrared (NIR) laser triggered photothermal
      ablation against infectious bacterial pathogens. Firstly, quaternized
      carboxymethyl chitosan (QCMC) not only acted as reducing agent to synthesize Au
      NPs, but also functioned as coupling agent to link up Au NPs with GO. Au-QCMC
      GO(+) was supposed to synergistically intensify the photothermal effect, which
      was then mixed with nanocellulose to form a functionalized paper via vacuum
      filtration. The photothermal efficiency, antibacterial treatment and mechanical
      property of Au-QCMC-GO(+)/nanocellulose paper were investigated. Excited by NIR
      laser irradiation, Au-QCMC-GO(+)/nanocellulose paper generated a temperature rise
      over 80  degrees C, sufficient for photothermal ablation upon both Gram-positive
      bacteria (Bacillus subtilis and Stapylococcus aureus) and Gram-negative bacteria
      (Escherichia coli and Pseudomonas aeruginosa). Additionally, Au-QCMC
      GO(+)/nanocellulose paper showed a remarkable enhancement in tensile strength,
      bursting index and tear index compared to those of pure nanocellulose paper.

PMID- 30092993
TI  - Chemico-physical and pharmacodynamic properties of extracellular Dictyosphaerium
      chlorelloides biopolymer.
AB  - Microalgae occupy all territories and their products represent a rich source of
      phytochemicals for human being. Green microalga Dictyosphaerium chlorelloides was
      found to be a significant producer of the extracellular biopolymer. Dominant
      components of the biopolymer were found to be Gal (39 wt%) with its methyl
      derivatives (15 wt%), Rha (19 wt%) and Man (14 wt%). 2-OMe-Gal was found to be
      the major derivative while other sugars, namely 3-OMe-, 6-OMe- and 2,3-di-OMe
      Gal, 3-OMe-Glc and 4-OMe-Xyl were in smaller amounts. NMR spectroscopy revealed
      complex structure with galactan backbone branched by sugars in furano and pyrano
      forms in alpha and beta configurations. NMR data of 2-OMe, 3-OMe, 2,3-OMe and 6
      OMe galactoses afforded characteristic values for O-methyls in each position.
      Biopolymer antitussive effect was similar to that of centrally acting antitussive
      drugs, indicating its relatively good antitussive potential.

PMID- 30092994
TI  - Antibacterial activity of PEO nanofibers incorporating polysaccharide from
      dandelion and its derivative.
AB  - A water-soluble antibacterial polysaccharide from dandelions (PD) was chemically
      modified to obtain its carboxymethylated derivative (CPD). The degree of
      substitution of CPD was 0.455. Fourier transform infrared (FTIR) spectra
      analysis, zeta potential, particle size and rheological test verified the
      carboxymethylation of PD, accompanying with the change of physicochemical
      properties. Moreover, Listeria monocytogenes treated with 10 mg/mL PD and CPD
      achieved 1.96 and 3.29 log CFU/mL reduction in population, respectively.
      Subsequently, PD and CPD were incorporated into polyethylene oxide (PEO)
      nanofiber matrix to fabricate antimicrobial nanofibers. The prepared nanofibers
      were characterized by scanning electron microscope, atomic force microscope and
      FTIR. Finally, both PD/PEO and CPD/PEO nanofibers exhibited favourable
      antibacterial effect on L. monocytogenes, with an improved antibacterial activity
      of CPD/PEO nanofibers than PD/PEO nanofibers. In conclusion, this study
      demonstrated PD and CPD could be applied to the fabrication of antibacterial food
      packaging.

PMID- 30092995
TI  - Recrystallization kinetics of starch microspheres prepared by temperature cycling
      in aqueous two-phase system.
AB  - The recrystallization behavior of starch microspheres (SMs) prepared by
      temperature cycling in aqueous two-phase system (ATPS) was investigated. The SMs
      were carried out under the temperature-cycled treatment at 4 degrees C, 30
      degrees C or 4/30 degrees C for 2 to 20 days. X-ray diffraction (XRD) results
      showed that the crystalline structure of SMs were different from that of degraded
      cassava starch. Compared to degraded cassava starch, the relative crystallinity
      of SMs under different temperature decreased, and the increase in relative
      crystallinity with the storage time was observed. All gelatinization temperature
      parameters (To, Tp and Tc) and enthalpy of gelatinization (DeltaH) of SMs
      decreased compared with degraded cassava starch. However, these values of SMs
      stored at 30 degrees C were higher than that of SMs stored at 4 degrees C and
      4/30 degrees C. The Avrami equation was applied to analysis the recrystallization
      behaviors of SMs. The stability test showed that the samples stored at 30 degrees
      C were more stable than that stored at 4  degrees C and 4/30 degrees C.

PMID- 30092996
TI  - Antibacterial and environmentally friendly chitosan/polyvinyl alcohol blend
      membranes for air filtration.
AB  - An antibacterial and environmentally friendly chitosan (CS) /polyvinyl alcohol
      (PVA) blend membrane for air filtration was prepared via nonsolvent induced phase
      separation (NIPS) method. The chemical structure, thermal behavior, morphology,
      mechanical property and surface charge of the resultant CS/PVA membranes were
      characterized. Results showed that CS and PVA were miscible due to the
      intermolecular hydrogen bond between them. The blend membrane obtained from over
      20 wt.% CS concentration exhibited a gradient interconnected porous structure
      without skin layer. The air filtration efficiency and pressure drop obtained from
      CS/PVA membrane with 30 wt.% CS concentration and the thickness of 37 MUm under a
      face velocity of 5.3 cm s-1 were 95.59% and 633.5 Pa, respectively. The
      performance of air filtration obtained is mainly attributed to the direct
      interception of membrane surface. Further, the antibacterial rate of the blend
      membrane was up to 94.8% for E. coli and 91.3% for S. aureus.

PMID- 30092997
TI  - Cellulose and nanocellulose-based flexible-hybrid printed electronics and
      conductive composites - A review.
AB  - Flexible-hybrid printed electronics (FHPE) is a rapidly growing discipline that
      may be described as the precise imprinting of electrically functional traces and
      components onto a substrate such as paper to create functional electronic
      devices. The mass production of low-cost devices and components such as
      environmental sensors, bio-sensors, actuators, lab on chip (LOCs), radio
      frequency identification (RFID) smart tags, light emitting diodes (LEDs), smart
      fabrics and labels, wallpaper, solar cells, fuel cells, and batteries are major
      driving factors for the industry. Using renewable and bio-friendly materials
      would be advantageous for both manufacturers and consumers with the increased use
      of (FHPE) electronics in our daily lives. This review article describes recent
      developments in cellulose and nanocellulose-based materials for FHPE, and the
      necessary developments required to propagate their use in commercial
      applications. The aim of these developments is to enable the creation of FHPE
      devices and components made almost entirely of cellulose materials.

PMID- 30092998
TI  - Cryogelation of alginate improved the freeze-thaw stability of oil-in-water
      emulsions.
AB  - Cryogelation of polysaccharide was hypothesized as a novel way to improve the
      freeze-thaw (FT) stability of emulsion. This hypothesis was tested using a
      cryogelling polysaccharide - alginate. In the absence of alginate, emulsions
      stabilized with Tween 20 and sugar esters were not stable against FT treatment.
      In the presence of alginate, improved stability of emulsions, i.e. less oiling
      off was observed after FT treatment at pH 5.0 where cryogelation was not
      occurred. However, significant improved stability, i.e. complete retarding of
      creaming, no oiling-off, and smaller emulsion droplet sizes were observed at pH
      3.5 and 3.0 where cryogelation was occurred. The improved FT stability was
      associated with the increased emulsions moduli due to cryogelation. The
      rheological properties of original emulsions were largely recovered by a heating
      processing at 35  degrees C for 2 h. Our results indicated that cryogelation of
      biopolymers could be used to improve the FT stability of emulsions.

PMID- 30092999
TI  - A strategy for strong interface bonding by 3D bioprinting of oppositely charged
      kappa-carrageenan and gelatin hydrogels.
AB  - A promising approach for improving the interfacial bonding of a three
      dimensionally (3D) printed multilayered structure has been investigated by taking
      advantage of the electrostatic interactions between two hydrogels with oppositely
      charges. Here, two hydrogels namely gelatin and kappa-carrageenan, which are the
      cationic and anionic hydrogels respectively, are used. It is found that the
      interfacial bonding strength between these two oppositely charged hydrogels is
      significantly higher than that of a bilayered gelatin or a bilayered kappa
      carrageenan. The bioprinted multilayered kappa-carrageenan-gelatin hydrogel
      construct demonstrates a very good biocompatibility and a good structure
      integrity at 37  degrees C. Our strategy also overcomes the limitation of using
      gelatin for bio-fabrication at 37  degrees C, without further post crosslinking.

PMID- 30093001
TI  - Influence of process parameters on microcapsule formation from chitosan-Type B
      gelatin complex coacervates.
AB  - A series of chitosan/gelatin based microcapsules containing n-hexadecane was
      synthesized through complex phase coacervation from chitosan (CH) and type-B
      gelatin (GB), and crosslinked by glutaraldehyde (GTA). This research was
      conducted to clarify the influence of different parameters on the encapsulation
      process, i.e., the emulsion formation and the shell formation, using zeta
      potential and surface tension measurements, attenuated total reflectance (ATR),
      and thermal analysis such as differential scanning calorimetry (DSC). The optimal
      values of biopolymer ratios (TBP), crosslinker amount, emulsion time and feeding
      weight ratio of core/shell polymer (RCS) were identified. The stability of the
      emulsion was depended on the surface activity and TBP ratio, which also affected
      the droplet size distribution and the thickness of the shell. Furthermore, core
      content, encapsulation efficiency and thermal properties of the microcapsules
      were related to TBP and RCS; with the lowest RCS giving the best microcapsules
      features.

PMID- 30093000
TI  - Characterization of pulp derived nanocellulose hydrogels using AVAP(r)
      technology.
AB  - Bioinspiration from hierarchical structures found in natural environments has
      heralded a new age of advanced functional materials. Nanocellulose has received
      significant attention due to the demand for high-performance materials with
      tailored mechanical, physical and biological properties. In this study,
      nanocellulose fibrils, nanocrystals and a novel mixture of fibrils and
      nanocrystals (blend) were prepared from softwood biomass using the AVAP(r)
      biorefinery technology. These materials were characterized using transmission and
      scanning electron microscopy, and atomic force microscopy. This analysis revealed
      a nano- and microarchitecture with extensive porosity. Notable differences
      included the nanocrystals exhibiting a compact packing of nanorods with reduced
      porosity. The NC blend exhibited porous fibrillar networks with interconnecting
      compact nanorods. Fourier transform infrared spectroscopy and X-ray diffraction
      confirmed a pure cellulose I structure. Thermal studies highlighted the excellent
      stability of all three NC materials with the nanocrystals having the highest
      decomposition temperature. Surface charge analysis revealed stable colloid
      suspensions. Rheological studies highlighted a dominance of elasticity in all
      variants, with the NC blend being more rigid than the NC fibrils and
      nanocrystals, indicating a double network hydrogel structure. Given these
      properties, it is thought that these materials show great potential in
      (bio)nanomaterial applications where careful control of microarchitecture,
      surface topography and porosity are required.

PMID- 30093002
TI  - Spectroscopic insight into supramolecular assemblies of boric acid derivatives
      and beta-cyclodextrin.
AB  - Interactions of select boric acid derivatives with beta-cyclodextrin were
      investigated. All products were obtained employing the grinding-induced
      mechanochemical approach. It was found that phenylboronic acid, benzoxaborole and
      boric acid form non-covalent, hydrogen bonding-based systems with beta
      cyclodextrin, whereas catechol and pinacol esters of phenylboronic acid as well
      as ferroceneboronic acid form host-guest inclusion complexes. The interactions
      were probed using spectroscopic methods: 1H NMR, 1H-1H ROESY NMR, 1H DOSY NMR, FT
      IR. Association constant values were evaluated by 1H DOSY NMR. The highest
      association constant was found for boric acid (117.5 +/- 2.5 M-1), whilst the
      lowest for benzoxaborole (14.8 +/- 0.3 M-1). The study shows the influence of
      boron compound structure on the nature of the assembly formed with beta
      cyclodextrin, laying up the basis for future work with such supramolecular
      systems.

PMID- 30093003
TI  - Rhizopus nigricans polysaccharide activated macrophages and suppressed tumor
      growth in CT26 tumor-bearing mice.
AB  - In this study, a homogeneous polysaccharide (RPS-1) was extracted from liquid
      cultured mycelia of Rhizopus nigricans. The weight-average molecular weight of
      RPS-1 was 1.617 * 107 g/mol and structural characterization indicated that RPS-1
      was a non-starch glucan which consisted of a backbone structure of (1->4)-linked
      alpha-d-glucopyranosyl residues substituted at the O-6 position with alpha-d
      glucopyranosyl branches. RPS-1 stimulated the production of nitric oxide and
      tumor necrosis factor-alpha by triggering phosphorylation of mitogen-activated
      protein kinases and nuclear translocation of nuclear factor kappa B p65 in RAW
      264.7 macrophage cells. Moreover, intragastric administration of RPS-1 improved
      the immune function of CT26 tumor-bearing mice and significantly inhibited the
      growth of transplanted tumor. In combination with 5-FU, RPS-1 enhanced antitumor
      activity of 5-FU and alleviated its toxicity on immune system. These findings
      suggested that RPS-1 has the potential for the development of functional foods
      and dietary supplements.

PMID- 30093004
TI  - Comparison of cellulose nanofiber properties produced from different parts of the
      oil palm tree.
AB  - Cellulose nanofibers (CNFs) were obtained from three types of oil palm wastes,
      mesocarp, empty fruit bunch (EFB), and palm kernel shell (PKS), as well as the
      trunk of the oil palm tree, to compare their morphological, thermal, and
      mechanical properties. Despite large differences in the chemical components of
      cell walls in the raw materials, the production of CNFs from all parts of the oil
      palm were achieved in this work. The morphology and mechanical properties of the
      CNF sheets obtained from the trunk had advantages over the CNF sheets from
      wastes, while the thermal degradation properties showed no advantage. Cellulose
      crystallinity of the CNF sheet from the mesocarp and PKS had lower crystallinity
      (69.1 and 71.1%), and the highest crystallinity of 77.0% was exhibited by the
      sheet from the trunk. The value of specific tensile strength and specific Young's
      modulus were highest in the CNF sheet of the trunk, and lowest mechanical
      properties shown in the CNF sheet from the mesocarp. These results strongly
      suggested that the CNF could be obtained from all parts of the plants, but their
      properties may vary.

PMID- 30093005
TI  - The effects of morpholine pre-treated and carboxymethylated cellulose nanofibrils
      on the properties of alginate-based hydrogels.
AB  - The effects of varying percentage loadings of morpholine pre-treated cellulose
      nanofibrils (MCNF) and carboxymethylated cellulose nanofibrils (CMCNF) on the
      aqueous swelling, compressive modulus and viscoelastic properties of calcium-ion
      crosslinked alginate hydrogels were investigated. In addition, the pore
      structures of hydrogels with the highest compressive modulus were studied. The
      incorporation of 5 wt. % MCNF resulted in a slightly reduced aqueous swelling, a
      36% increase in compressive modulus and a layered pore structure when compared
      with the neat alginate hydrogel. On the other hand, the addition of CMCNF at the
      same loading led to a slightly improved aqueous swelling, an increase in
      compressive modulus (17%) and high porosity. Further increases in CNF loadings
      did not result in significant increase in material properties. The alginate/CNF
      composite materials have potentials to be used in applications where good
      swelling and mechanical robustness are required.

PMID- 30093006
TI  - Corrigendum to "Structural, mechanical and enzymatic study of pectin and
      cellulose during mango ripening" [Carbohydr. Polym. 196 (2018) 313-321].

PMID- 30093007
TI  - The inhibitory effects and mechanisms of 3,6-O-sulfated chitosan against human
      papillomavirus infection.
AB  - High-risk human papillomavirus (HPV) infection can lead to the development of
      cervical cancers that are a significant health burden worldwide. The heparin-like
      polysaccharides such as dextran sulfate and carrageenan were reported to be able
      to prevent the binding of HPV to the cell surface. In this study, a 3,6-O
      sulfated chitosan (36S) was prepared, and its anti-HPV effects were explored. The
      results showed that 36S effectively inhibited multiple genital HPV genotypes in
      different cell lines with low cytotoxicity. 36S may possibly block HPV adsorption
      via direct binding to the viral capsid proteins. 36S could enter into Hela cells
      and down-regulate cellular PI3K/Akt/mTOR pathway which is associated with
      autophagy. Thus, marine derived sulfated chitosan 36S possessed broad anti-HPV
      activities in vitro, and may possibly inhibit HPV infection by targeting viral
      capsid protein and host PI3K/Akt/mTOR pathway, suggesting that 36S merits further
      investigation as a novel anti-HPV agent.

PMID- 30093008
TI  - In vivo monitoring of tumor distribution of hyaluronan polymeric micelles labeled
      or loaded with near-infrared fluorescence dye.
AB  - Development of delivery systems which allow real-time visual inspection of tumors
      is critical for effective therapy. Near-infrared (NIR) fluorophores have a great
      potential for such an application. To overcome NIR dyes short blood circulation
      time and increase tumor accumulation, a NIR dye, cypate, was associated with
      oleyl hyaluronan, which can self-assemble into polymeric aggregates. The cypate
      association with oleyl hyaluronan was performed either by a covalent linkage, or
      physical entrapment. The two systems were compared for tumor targeting and
      contrast enhancement using BALB/c mice bearing 4T1 breast cancer tumors.
      Independently on the way of cypate association, it took more than 24 h from
      intravenous administration to detect NIR signal in tumors and the tumors were
      clearly visualized for 2 following weeks without substrate reinjection.
      Covalently linked cypate generated 2-3 fold stronger fluorescence signal than
      physically loaded cypate. This study demonstrates the potential of HA matrix to
      be used as carrier of contrast agents for non-invasive long-term tumor
      visualization.

PMID- 30093009
TI  - Cationization of lignocellulosic fibers with betaine in deep eutectic solvent:
      Facile route to charge stabilized cellulose and wood nanofibers.
AB  - In this study, a deep eutectic solvent (DES [based on triethylmethylammonium
      chloride (TEMA) and imidazole]) was used as a reaction medium for cationization
      of cellulose fibers with trimethylglycine (betaine) hydrochloride in the presence
      of p-Toluenesulfonyl (tosyl) chloride. Cellulose betaine ester with a cationic
      charge up to 1.95 mmol/g was obtained at mild reaction conditions (four hours at
      80  degrees C). The reaction was further demonstrated in the fabrication of
      cationic cellulose nanofibers (CCNFs) by a mild mechanical disintegration of
      cationized cellulose. In addition to CCNFs, cationic wood nanofibers (CWNFs) were
      produced directly from groundwood pulp (GWP) with a high lignin content (27 w%).
      Individualized CCNFs and CWNFs had a fiber diameter of 4.7 +/- 2.0 and 3.6 +/-
      1.3 nm, respectively, whereas some larger fiber aggregates (diameter below 200
      nm) were also observed, especially in the case of CWNFs.

PMID- 30093010
TI  - Recyclable ferromagnetic chitosan nanozyme for decomposing phenol.
AB  - Decomposing phenol and phenolic compounds to purify the environment is a focus of
      social attention. The use of ferromagnetic nanoparticles (MNP) to degrade phenol
      and phenolic compounds possesses many advantages and has received extensive
      attention. However, the unsatisfied catalyst activity and stability of MNP hamper
      its industrial applications. To improve MNP's properties, a ferromagnetic
      chitosan nanozyme (MNP@CTS) was synthesized via an improved hydrothermal method
      and molecular self-assembly technology. Its particle size was 11.76 nm,
      polydispersity index (PDI) was 0.073, surface zeta potential was 40.34 mV,
      saturation magnetization value was 35.28 emu g-1 and coercivity value was 17.56
      Oe. The catalytic condition was extensively optimized among a range of pH and
      temperature, as well as initial concentrations of the substrate and H2O2, and
      MNP@CTS removed over 95% phenol from an aqueous solution within 5 h under the
      optimum conditions. Moreover, MNP@CTS was stable and could be regenerated for
      reuse for at least ten rounds. Thus, our findings open up a wide spectrum and lay
      a foundation of environmental friendly applications of MNP@CTS, showing several
      attractive features, such as easy preparation, low cost, excellent catalytic
      activity, good stability and reusability.

PMID- 30093011
TI  - Lower range of molecular weight of xanthan gum inhibits cartilage matrix
      destruction via intrinsic bax-mitochondria cytochrome c-caspase pathway.
AB  - We have previously reported an application of lower range of molecular weight of
      xanthan gum (LRWXG) for inhibiting cartilage matrix destruction and preventing
      mitochondrial damage in rabbit osteoarthritis (OA) model. However, whether LRWXG
      exerts its anti-OA activity through intrinsic bax-mitochondria cytochrome c
      caspase signaling pathway in OA still requires further study. To address this
      problem, the OA model was induced by anterior cruciate ligament transection
      (ACLT) in rabbit and then treated with LRWXG. The results showed that LRWXG could
      inhibit the loss of collagen in cartilage matrix, protect trabecular bone in
      subchondral, decrease the apoptosis of chondrocytes, down-regulate the
      expressions of active caspase-9, active caspase-3 and bax, and up-regulate the
      expression of bcl-2. In addition, LRWXG could up-regulate the expression of cyt-c
      in mitochondria, while down-regulate the expression of cyt-c in cytoplasm. These
      findings show that LRWXG inhibits cartilage degradation via an intrinsic bax
      mitochondria cytochrome c-caspase pathway in OA.

PMID- 30093012
TI  - Sustainable nitrogen-rich hierarchical porous carbon nest for supercapacitor
      application.
AB  - Chitosan has high synthetic flexibility, making it a promising nitrogenous
      bioresource for industrial applications. Nitrogen-rich hierarchically porous
      carbon (NHPC) was successfully synthesized by hydrothermal carbonization and self
      activation of a chitosan-transition metal ion (Zn2+) complex. The N2 adsorption
      desorption isotherm revealed that the as-made NHPC had large specific surface
      area (1067 m2 g-1) and a unique hierarchical pore structure (0.6-6.4 nm).
      Scanning electron microscopy (SEM) indicated a 3D finely interconnected nest
      architecture for NHPC. X-ray photoelectron spectroscopy (XPS) analysis
      demonstrated that the nitrogen atoms in the chitosan were protected by
      coordination with zinc ions, and most of them were still retained in the carbon
      matrix (6.36 at%) after high temperature activation. Electrochemical measurements
      exhibited that NHPC delivers a high specific capacitance (228.7 Fg-1 at 1 A g-1),
      impressive rate capability (the specific capacitance at 20 A g-1 was 174 Fg-1,
      maintaining 74.6% of the initial capacitance at 0.5 A g-1), and outstanding long
      term cycling stability (98.3% retention after 5000 cycles), together with
      excellent energy density of 25.7 Wh kg-1 at the power density of 500 W kg-1. This
      study offers a novel strategy for synthesizing NHPC as one of the desirable
      electrode material candidates for energy storage.

PMID- 30093014
TI  - Carrageenan based hydrogels for drug delivery, tissue engineering and wound
      healing.
AB  - Carrageenan is a class of naturally occurring sulphated polysaccharides, which is
      currently a promising candidate in tissue engineering and regenerative medicine
      as it resemblances native glycosaminoglycans. From pharmaceutical drug
      formulations to tissue engineered scaffolds, carrageenan has broad range of
      applications. Here we provide an overview of developing various forms of
      carrageenan based hydrogels. We focus on how these fabrication processes has an
      effect on physiochemical properties of the hydrogel. We outline the application
      of these hydrogels not only pertaining to sustained drug release but also their
      application in bone and cartilage tissue engineering as well as in wound healing
      and antimicrobial formulations. Administration of these hydrogels through various
      routes for drug delivery applications has been critically reviewed. Finally, we
      conclude by summarizing the current and future outlook that promotes the seaweed
      derived polysaccharide as versatile, promising biomaterial for a variety of
      bioengineering applications.

PMID- 30093013
TI  - Modification of potato starch by using superheated steam.
AB  - Conventional hydrothermal modification of starches is a time- and energy
      consuming process. In this study, superheated steam (SS) at different
      temperatures (100-160 C) was used to modify the structural and physicochemical
      properties of potato starch (PS). The long- and short-range molecular structures
      were disrupted without affecting the granular structure of PS and the degree of
      disruption could be regulated by simply changing the treatment temperature. The
      swelling power, solubility, transparency, peak viscosity and breakdown of PS were
      positively correlated with each other and were significantly decreased by SS
      treatment, while the pasting temperature, final viscosity and setback were
      significantly increased. Considerable amount (>9%) of slowly digestible starch
      was converted to resistant starch by SS treatment at 100 and 120  degrees C.
      Considering the high thermal efficiency of SS and the short treatment time (1 h)
      used in this study, SS treatment could be a superior alternative to conventional
      hydrothermal modification.

PMID- 30093015
TI  - Mesoporous zeolite-chitosan composite for enhanced capture and catalytic activity
      in chemical fixation of CO2.
AB  - Carbon dioxide is one of the greenhouse gases whose increasing concentration in
      the atmosphere can cause severe problems to both human health and wildlife. A
      simple ecofriendly procedure was developed to prepare zeolite-chitosan (ZY-CS)
      composite using solvent exchange followed by calcination for adsorption and
      chemical fixation of CO2. The as synthesized ZY-CS composite along with zeolite
      and chitosan were characterized by attenuated total reflection infrared, X-ray
      diffraction, thermogravimetric, scanning electron microscopy, high-resolution
      transmission electron microscopy and nitrogen adsorption-desorption isotherms
      studies. The ZY-CS composite showed enhanced CO2 adsorption capacity compared
      with pure zeolite and chitosan. The composites also exhibited significant
      catalytic activity in the chemical fixation of CO2 into cyclic carbonates. This
      work is foreshadowing the prospect of ZY-CS composite in enhanced capture and
      catalytic activity in chemical fixation of CO2 for environmental applications.

PMID- 30093017
TI  - Integration of graft copolymerization and ring-opening reaction: A mild and
      effective preparation strategy for "clickable" cellulose fibers.
AB  - A mild and effective strategy to prepare alkynyl-functionalized cellulose fibers
      (A-CFs) and azido-functionalized cellulose fibers (N3-CFs) was presented. Epoxy
      cellulose fibers (Epoxy-CFs), graft copolymerization products of cellulose fibers
      (CFs) and glycidyl methacrylate (GMA), were prepared using cerium ammonium
      nitrate (CAN) as initiator. Epoxy groups content of Epoxy-CFs were as high as 2.5
      mmol/g. Introduction of alkynyl/azido groups into Epoxy-CFs were achieved through
      ring-opening reactions of epoxy groups with propargylamine (PgAm) and sodium
      azide (NaN3), respectively. Under appropriate conditions, A-CFs with alkynyl
      groups of 0.57 mmol/g and N3-CFs with azido groups of 0.35 mmol/g were obtained.
      Click reactivities of A-CFs, N3-CFs and Epoxy-CFs were verified by Cu(I)
      catalyzed alkyne-azido cycloaddition (CuAAC) and thiol-epoxy click reactions. A
      CFs, N3-CFs, Epoxy-CFs and their clicked products were characterized by
      attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR)
      and X-ray photoelectron spectroscopy (XPS).

PMID- 30093016
TI  - Selenized polysaccharides - Biosynthesis and structural analysis.
AB  - The main objective of our research was to analyze the structure of the Se
      containing polysaccharides and to examine how the selenium is bound to the
      polysaccharide molecule. During investigation of the biosynthesis of new
      immunomodulators, we isolated a selenium (Se)-containing polysaccharide-protein
      fraction containing proteoglycans of molecular weights of 3.9 * 106 Da and 2.6 *
      105 Da, composed of glucose or mannose, nearly 8% of protein and 190 MUg Se/g dry
      weight. X-ray absorption spectroscopy (XAS) data analysis in the near edge region
      (XANES) confirmed that selenium in the Se-polysaccharides structure is present at
      the -II oxidation state and that Se is organically bound. The simulation analysis
      in the EXAFS (extended X-ray absorption fine structure) region suggested that
      selenium is most likely bound by a glycosidic-link in a beta-1,3 or alpha-1,4
      glycosidic bond or substituted for oxygen in a pyranosidic ring. Calculations
      performed with Gaussian 03 software predicted deformations in the polysaccharide
      structure caused by the incorporation of the selenium atom including change in
      bond lengths and torsion angles and, as a result, disappearance of hydrogen bonds
      in the vicinity of the selenium atoms.

PMID- 30093018
TI  - Mesalazine/hydroxypropyl-beta-cyclodextrin/chitosan nanoparticles with sustained
      release and enhanced anti-inflammation activity.
AB  - This study aimed to develop a novel sustained release system for mesalazine (MSZ)
      by preparing hydroxypropyl-beta-cyclodextrin (HP-beta-CD) inclusion complex
      loaded chitosan (CS) nanoparticles (NPs). The HP-beta-CD/MSZ complex was prepared
      at 1:1 stoichiometry and characterized by using various analysis techniques. The
      HP-beta-CD/MSZ/CS NPs prepared under the optimum condition had a spherical shape
      (90+/-17 nm diameter), a narrow size distribution, and a high loading efficiency.
      Compared with free MSZ, the HP-beta-CD/MSZ/CS NPs exhibited an obvious sustained
      release of MSZ. The activity of the NPs against a cytokine-triggered inflammatory
      response was evaluated in cytokine-stimulated HT-29 cell lines by monitoring key
      inflammatory mediators. The results revealed that compared with free MSZ, the NPs
      more strongly inhibited the production of NO, PGE2, and IL-8, indicating the NPs
      possibly had better anti-inflammatory effects. Therefore, the established HP-beta
      CD/MSZ/CS NPs may be a promising delivery system of MSZ.

PMID- 30093019
TI  - Effect of culture conditions on the physicochemical properties and antioxidant
      activities of polysaccharides from Nostoc flagelliforme.
AB  - Three polysaccharides (WL-CPS-1, NaCl-CPS-1 and Glu-CPS-1) were extracted and
      purified from Nostoc flagelliforme under normal, salt stress and mixotrophic
      culture conditions respectively. Their physicochemical properties and antioxidant
      activities were investigated. WL-CPS-1, NaCl-CPS-1 and Glu-CPS-1 chemical
      composition differed in sugar and uronic acid contents, and they were composed of
      nine constituent monosaccharides and one uronic acid with different ratios, with
      the average molecular weights of 1.02 * 103, 1.12 * 103 and 1.33 * 103 kDa,
      respectively. They presented similar fourier transform infrared spectra, but
      different surface morphology, chain length and branching. Antioxidant assay
      showed that they all exhibited strong scavenging activity on ABTS+ and hydroxyl
      radicals and moderate activity on DPPH radical. Glu-CPS-1 exhibited the highest
      antioxidant activity suggested culture conditions could regulate the bioactivity
      through influencing the structure and properties. These findings demonstrated the
      potential application of proper regulation of culture conditions in the
      development of polysaccharides with high antioxidant activity.

PMID- 30093020
TI  - Colon-targeted dexamethasone microcrystals with pH-sensitive
      chitosan/alginate/Eudragit S multilayers for the treatment of inflammatory bowel
      disease.
AB  - Oral colon-targeted drug delivery has gained popularity as an effective strategy
      for treatment of inflammatory bowel disease (IBD). In this study, we prepared
      colon-targeted dexamethasone microcrystals (DXMCs) coated with multilayers of
      chitosan oligosaccharide (CH), alginate (AG), and finally Eudragit S 100 (ES)
      (ES1AG4CH5-DXMCs) using a layer-by-layer (LBL) coating technique. Particle size,
      surface charge, in vitro drug release, and in vivo anti-inflammatory activity of
      ES1AG4CH5-DXMCs were evaluated. ES1AG4CH5-DXMCs had an average particle size of
      2.34 +/- 0.19 MUm and a negative surface charge of - 48 +/- 9 mV. ES1AG4CH5-DXMCs
      demonstrated pH-dependent dexamethasone release, avoiding initial burst drug
      release in acidic pH conditions of the stomach and small intestine, and providing
      subsequent sustained drug release in the colonic pH. Importantly, ES1AG4CH5-DXMCs
      exhibited a significant therapeutic activity in a mouse model of colitis compared
      to other DXMCs. Overall, the LBL-coated DXMCs presented here could be a promising
      colon-targeted therapy for IBD.

PMID- 30093021
TI  - Fabrication of porous chitin membrane using ionic liquid and subsequent
      characterization and modelling studies.
AB  - The application of green chemistry principles for the processing of biopolymers
      is a steadily increasing field of research. Chitin membranes were successfully
      prepared by using the ionic liquid 1-ethyl-3-methylimidazolium acetate
      ([C2mim][OAc]) as solvent media. The resulting materials were thoroughly
      characterized, revealing that freeze drying produced membranes that were highly
      porous. The drying methods and the concentration of chitin used defined many of
      the membrane properties, such as mechanical strength, porosity, and water
      absorbency. From these data, an empirical model was generated which could be used
      to correlate the different membrane properties. The model could be used to
      predict the properties of the chitin membrane made with different wt% of chitin
      IL solutions, and the predicted values aligned with the experimental results.
      This allowed for prediction of the properties of the chitin membrane (e.g.,
      tensile strength) and gives the ability to tune the properties of the
      biomaterial. The methods and structures described here provide a starting point
      for the design and fabrication of a family of polysaccharide-based sustainable
      materials with potentially broad applicability.

PMID- 30093022
TI  - Structural characterization and antidiabetic potential of a novel
      heteropolysaccharide from Grifola frondosa via IRS1/PI3K-JNK signaling pathways.
AB  - A novel heteropolysaccharide from Grifola frondosa named GFP-W has been isolated
      and purified by DEAE Sephadex A-52 chromatography. Gas chromatography, fourier
      transform infrared spectroscopy, one-dimensional (1H- and 13C-) and two
      dimensional (1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC) nuclear magnetic resonance
      spectroscopy were used to characterize its structure. The average molecular
      weight of GFP-W was 66.1 kDa. GFP-W mainly contained four kinds of linkage type
      units as beta-D-GlcpA->, 1,2,6-alpha-Gal, ->2)-alpha-Manp->, and ->3)-alpha-L
      Fucp-(1->. It could significantly increase the uptake of glucose in dexamethasone
      induced insulin resistant HepG2 cells by improving the mRNA and protein
      expression of insulin receptor substrate 1, phosphatidylinositol-3-kinase, and
      glucose transporter 4 upregulation and c-Jun N-terminal Kinase 1 downregulation.
      Moreover, antidiabetic activities of GFP-W were associated with significant
      changes in the extent of protein lysine acetylation, crotonylation, and
      succinylation levels. Our results provide a new hypoglycemic therapeutic role and
      an in-depth analysis on molecular mechanisms upon polysaccharides from G.
      frondosa.

PMID- 30093023
TI  - Antibacterial effectiveness meets improved mechanical properties: Manuka
      honey/gellan gum composite hydrogels for cartilage repair.
AB  - Biomaterials for cartilage repair are still far from clinical requirements, even
      if several studies recently focused on this topic. In this respect, Nature
      derived hydrogels are a promising class of scaffolds for cartilage tissue
      engineering, mimicking the native cellular microenvironment. However, they
      frequently lack mechanical features required for cartilage applications and are
      commonly subjected to infection threat. This work describes the innovative use of
      Manuka honey as molecular spacer for preparing gellan gum-based composites with
      intrinsic antibacterial properties and superior compressive Young's modulus in
      respect of several Nature-derived gels based on chitosan, hyaluronic acid or
      alginate. The addition of Manuka honey made hydrogels able to inhibit the
      proliferation of S. aureus and S. epidermidis clinical isolates. Furthermore, no
      cytotoxic effects were detected on human mesenchymal stem cells seeded on the
      hydrogels. Moreover, chondrogenesis experiments showed a consistent expression of
      collagen II and high synthesis of GAGs and proteoglycans, thus indicating the
      formation of cartilage matrix. Overall, these data suggest that the developed
      smart composites have a great potential as tools for cartilage tissue
      engineering.

PMID- 30093024
TI  - Physicochemical properties and flavor retention ability of alkaline calcium
      hydroxide-mungbean starch films.
AB  - The physicochemical properties and the flavor retention ability of the dried
      mungbean starch film formed in the presence of calcium ions under alkaline pH
      were analyzed. Treating starch in a NaOH or Ca(OH)2 solution at pH 12 induced the
      formation B-type starch crystal. However, the starch film made with Ca(OH)2 (Ca
      film) was more effective than starch film made with NaOH (Na-film) in entrapping
      1,8-cineole, menthone and citonellol. Entrapment efficiency of citonellol in Ca
      film which had B-type starch crystal structure was close to that of the V-type
      starch film formed at neutral pH using distilled water (DW-film). 1,8-cineole,
      menthone, and citronellol were entrapped in dried Ca-films for 5.07%, 1.52%, and
      30.84%, respectively. Physical entrapment of flavor compounds by alkaline-treated
      starch and high water solubility (24.4-46.7 %) of Ca-films could help designing a
      novel controlled flavor release systems.

PMID- 30093025
TI  - Facile fabrication of sulfated alginate electrospun nanofibers.
AB  - Mass fabrication of sodium alginate nanofibers using single-nuzzle
      electrospinning process is an open challenge mainly due to its inter- and
      intramolecular hydrogen bonding, rigid chain conformation and low solubility. In
      this regards, we synthesized sodium sulfated alginate (SSA) through sulfation of
      hydroxyl functional groups of alginate. Not only decreases the hydrogen bonding
      density through the sulfation reaction, but the sulfated alginate also
      demonstrates more solubility in aqueous media compared to the pristine alginate.
      Beside the sulfation of alginate, its electrospinnability in combination with
      polyvinyl alcohol (PVA) significantly improves. In contrast to the neat alginate,
      concentrated aqueous solutions of sulfated alginate, 10 wt%, can be easily
      prepared and electrospun to obtain nanofibers of sulfated alginate. In this
      regards, facile fabrication of electrospun nanofibers of alginate derivatives
      with 50 wt% content in dry electrospun mat of SSA/PVA using single-nuzzle
      electrospinning and flow rate of 5 mL h-1 was developed for the first time.

PMID- 30093026
TI  - Preparation of injectable hydrogels from temperature and pH responsive grafted
      chitosan with tuned gelation temperature suitable for tumor acidic environment.
AB  - In this present work, stimuli responsive polymers that can respond to the
      temperature and pH of the environment were prepared. A series of temperature
      responsive diblock copolymers based on poly(ethylene glycol) methyl ether (mPEG)
      and epsilon-caprolactone (CL) were synthesized. Subsequently, the diblock
      copolymers were grafted onto chitosan, a pH responsive biopolymer. These chitosan
      graft-(mPEG-block-PCL) (chitosan-g-(mPEG-b-PCL)) graft copolymers were
      structurally characterized by 1H NMR and FTIR and their sol-gel phase transitions
      were analyzed by the test tube inversion method as well as dynamic rheological
      measurements. These chitosan-g-(mPEG-b-PCL) graft copolymers demonstrated tunable
      temperature and pH responsive sol-gel phase transitions that correspond well with
      body temperature and pH of acidic tumor microenvironments. Gelation temperature
      (Tgel) decreased with increasing pH of the system, increasing PCL composition in
      the diblock copolymers, increasing solution concentration and decreasing grafting
      content of the diblock copolymers on chitosan. The graft copolymer hydrogels
      successfully showed the sustained release of both doxorubicin and curcumin for up
      to 2 weeks. The designed system was based on chitosan-g-(mPEG-b-PCL) graft
      copolymers, of which chitosan showed pH responsive properties and mPEG-b-PCL
      acted as a temperature sensitive moiety. In addition, mPEG and PCL are recognized
      as biocompatible polymers and chitosan has been engaged in various pharmaceutical
      research. Thus, this system could be considered an alternative choice for drug
      delivery applications.

PMID- 30093028
TI  - Controlling alginate oxidation conditions for making alginate-gelatin hydrogels.
AB  - In the present work, we discuss how oxidation conditions can affect the physical
      properties of oxidized alginate and crosslinking it with gelatin. We show that
      the amount of aldehyde groups produced on oxidized alginate backbone increases by
      increasing alginate concentration even in constant molar ratio of sodium
      periodate to alginate's repeating units. Increasing the concentration of alginate
      solution, promote the extent of chain scission and decreases the molecular weight
      of oxidized alginate, which can be due to the increased possibility of molecular
      collisions and oxidizing two adjacent uronic acids in the chain. By changing the
      oxidation condition, therefore, we can produce oxidized alginate with same degree
      of oxidation but different molecular weights, which change the sol-gel state of
      alginate-gelatin mixtures. Using oxidized alginates with different molecular
      weights, we suggest that the aldehyde end groups in alginate chains have the
      dominant effect in crosslinking with gelatin.

PMID- 30093027
TI  - Facile and green synthesis of pullulan derivative-stabilized Au nanoparticles as
      drug carriers for enhancing anticancer activity.
AB  - In this work, we report for the first time AuNPs reduced/stabilized/capped with
      modified para-aminobenzoic acid-quat188-pullulan (PABA-QP) as excellent
      nanocarriers for delivery of doxorubicin to enhance the activity and safety of
      these systems. Spherical AuNPs@PABA-QP obtained by facile and green synthesis
      under optimum conditions were characterized by UV-VIS, TEM, EDS, SAED, XRD, ATR
      FTIR and zeta-potential analyses and showed a narrow size distribution of 13.7 +/
      1.9 nm. DOX was successfully loaded onto AuNPs@PABA-QP via intermolecular
      interactions with high drug loading. DOX-AuNPs@PABA-QP (IC50 = 0.39MUM) showed a
      2.1-fold higher cytotoxicity against Chago cells than DOX alone (IC50 = 0.82MUM),
      while exhibiting less cytotoxicity against normal cells (Wi-38). Moreover, DOX
      AuNPs@PABA-QP also demonstrated high intracellular uptake by endocytosis,
      arrested in S and G2-M phases of the cell cycle (total S/G2-M increased to
      approximately 18.0%), induced excellent cytotoxicity, and increased the fraction
      of late-apoptotic cells (18.6%). Consequently, it is suggested that the novel
      combination of DOX-AuNPs@PABA-QP has the potential to be developed for human
      cancer treatment.

PMID- 30093029
TI  - Interaction of polyelectrolyte complex between sodium alginate and chitosan
      dimers with a single glyphosate molecule: A DFT and NBO study.
AB  - The formation of a polyelectrolyte complex through dimers of alginate and
      chitosan in the presence of sodium cations (SA/CS), and its interaction with the
      glyphosate herbicide, has been investigated at the DFT level (B3LYP/6
      311+G(d,p)). The lowest energy structure for SA/CS presents one Na+ cation
      coordinated to both dimers and formation of two H-bonds involving COO- and NH3+.
      The coordination energy of Na+ contributes with about 40% of the total complex
      stabilization energy. LMOEDA method indicates important contribution of covalent
      nature to stabilization of SA/CS. This result is corroborated by NBO analysis
      which shows high contribution of lp(O)->sigma*(NH) overlapping, with average
      energy of 30 kcal mol-1 for the formed H-bonds. Two water molecules neighboring
      the complex increases its stability and promotes an octahedral coordination
      arrangement around Na+. The glyphosate interacts with SA/CS coordinating to Na+
      and bonding to the chitosan dimer by H-bond, in agreement to performed
      fluorescence microscopy measurements.

PMID- 30093030
TI  - Methylene blue removal from water using the hydrogel beads of poly(vinyl alcohol)
      sodium alginate-chitosan-montmorillonite.
AB  - Poly(vinyl alcohol)-sodium alginate-chitosan-montmorillonite nanosheets (MMTNS)
      hydrogel beads with porous and steady structure were fabricated via hydrogen-bond
      and electrostatic interactions, and were characterized by FTIR, TG, SEM and
      effecting tests. The results suggested MMTNS could support and maintain the
      porous structure, making an open excess for MB molecules. The increasing
      proportion of MMTNS in hydrogel beads enhanced the MB removal. Hydrogel beads
      possessed higher affinity to MB at high pHs due to the stronger electronegativity
      triggered by deprotonation of hydroxyls. Moreover, hydrogel beads had a good
      stability and reusability. The adsorption process was correlated with Elovich
      kinetics model, and fitted well with Freundlich, Redlich-Peterson and Sips
      isotherm models. The adsorption of MB on hydrogel beads was a disorderliness,
      endothermic and spontaneous process detected by the thrmodynamic. MB molecules
      reacted with the oxygen atoms in hydroxyl and substitute the Na+ in MMTNS were
      proved by EDS, XPS and Na+ concentration variation.

PMID- 30093031
TI  - Purification, characterization and antioxidant activity of dextran produced by
      Leuconostoc pseudomesenteroides from homemade wine.
AB  - An exopolysaccharide (EPS) was produced by Leuconostoc pseudomesenteroides DRP-5
      isolated from homemade wine. The EPS was obtained with ethanol extraction, which
      was further purified by chromatography of Sephadex G-100 to get a purified
      fraction. The monosaccharide composition of the EPS was glucose, and its
      molecular weight (Mw) was 6.23 * 106 Da, as determined by gas chromatography (GC)
      and high-performance size-exclusion chromatography (HPSEC). Fourier transform
      infrared spectra (FT-IR) and nuclear magnetic resonance spectra (NMR) showed that
      the EPS was a linear glucan with alpha-(1->6)-linked glucosidic bonds. The water
      holding capacity (WHC), water solubility index (WSI) and emulsifying activity
      (EA) of DRP-5 EPS were 296.76 +/- 18.93%, 98.62 +/- 3.57% and 87.22 +/- 2.18%,
      respectively. DRP-5 EPS have a higher degradation temperature of 278.36  degrees
      C, suggesting high thermal stability of the EPS. Also, DRP-5 EPS was found to
      have moderate 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydroxyl radical,
      superoxide anion radical, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate)
      (ABTS) radical, Fe2+ scavenging activities and reducing power. All these
      characteristics suggest that DRP-5 EPS might have potential applications in the
      pharmaceutical, cosmetic and food industries.

PMID- 30093033
TI  - Bio-inspired functionalization of microcrystalline cellulose aerogel with high
      adsorption performance toward dyes.
AB  - As one of the materials from natural resources, the functionalization and
      application of cellulose attract increasing concerns. In this work, we reported a
      facile method to prepare the bio-inspired functionalization of microcrystalline
      cellulose (MCC) aerogel through polydopamine (PDA) coating, which was realized
      via the self-polymerization of dopamine in the MCC/LiBr solution followed by the
      freeze-drying technology. The morphological characterization showed that the pore
      morphologies of the compounded aerogel were influenced by the content of PDA.
      Adsorption measurements toward methylene blue (MB) showed that the compounded
      aerogel had high adsorption ability. Moreover, the compounded MCC/PDA aerogel
      exhibited excellent adsorption selectivity and it exhibited high efficiency to
      remove MB from different solutions, such as the mixed solution with anionic
      dyestuffs, the mixed solution with cationic dyestuffs and the mixed solution with
      common salt (NaCl). The high adsorption ability and excellent adsorption
      selectivity endows the compounded MCC/PDA aerogel with great potential
      applications in wastewater treatment.

PMID- 30093032
TI  - Enhanced cytotoxic and apoptotic potential in hepatic carcinoma cells of chitosan
      nanoparticles loaded with ginsenoside compound K.
AB  - Ginsenoside compound K (CK) has been shown to exhibit anticancer properties. In
      this study, chitosan nanoparticles loaded with ginsenoside compound K (CK-NPs)
      were prepared as a delivery system using a self-assembly technique with
      amphipathic deoxycholic acid-O carboxymethyl chitosan as the carrier, which
      improved the water solubility of CK. By evaluating drug loading, entrapment
      efficiency, and in vitro release behavior, the feasibility of CK-NPs as a drug
      carrier nanoparticle for the treatment of human hepatic carcinoma cells (HepG2)
      was investigated. Result revealed that CK and CK-NPs showed a dose-dependent
      inhibitory effect on HepG2 cells with IC50 values of 23.33 and 16.58 MUg/mL,
      respectively. Furthermore, fluorescence imaging demonstrated that CK-NPs promoted
      cellular uptake in vitro. Therefore, all results indicated that CK-NPs might be a
      novel drug delivery system to improve the solubility and enhance the cytotoxic
      and apoptotic potentials of CK for effective liver cancer chemotherapy.

PMID- 30093034
TI  - Production and characterization of supercritical CO2 dried chitosan nanoparticles
      as novel carrier device.
AB  - The materials produced by the supercritical CO2 drying have outstanding
      properties that allow the incorporation of molecules in their porous structure.
      In this context, dried chitosan nanoparticles including beta-lactoglobulin were
      obtained. First, the nanoparticles in water suspension were produced by
      ionotropic gelation incorporating the protein with high loading efficiency.
      Later, solvent exchange and CO2 supercritical drying procedures were performed.
      The physicochemical characteristics and structural properties were determined,
      demonstrating a stable porous structure in the dried materials and corroborating
      the presence of the protein after the drying. The CO2 supercritical dried
      chitosan nanoparticles can be effectively resuspended in acidic aqueous medium
      remaining in the nanoscale with minimum effect on the loading parameters. The
      release of the beta-lactoglobulin was highly influenced by the pH, reaching
      around 40% under acidic conditions in ten hours. The obtained results demonstrate
      the possibility to apply these chitosan materials as a controlled release
      material.

PMID- 30093035
TI  - Triple-crosslinkedbeta-cyclodextrin oligomer self-healing hydrogel showing high
      mechanical strength, enhanced stability and pH responsiveness.
AB  - A novel self-healing hydrogel was prepared from a cationic beta-cyclodextrin
      oligomer allyl ether [C(betaCD-OM)AE] using a triple cross-linking strategy
      combining electrostatic interaction, host-guest complexation, and CC bonds as the
      macrocrosslinker. Here, the C(betaCD-OM)AE@Ad gel was successfully prepared by
      polymerization of synthesized C(betaCD-OM)AE, 1-adamantyl acrylate, and acrylic
      acid. The triple cross-linked hydrogel shows multi-functionality of high
      mechanical strength, enhanced stability, cytocompatibility, pH responsiveness as
      well as self-healing ability. Based on the cooperative and synergetic forces of
      non-covalent and covalent bonds, the C(betaCD-OM)AE@Ad gel shows a high tensile
      strain up to 1,590%, and the self-healed gel could restore up to 84% of its
      initial length within 24 h. Furthermore, drug release in the hydrogel was
      controlled by the surrounding pH and slowly released. The present work reveals
      the cooperativity of multiple cross-links for a 3D structured polymeric material,
      and the developed self-healable hydrogel can possibly be applied in various
      biomedical applications.

PMID- 30093036
TI  - Effect of solution plasma process with hydrogen peroxide on the degradation of
      water-soluble polysaccharide from Auricularia auricula. II: Solution conformation
      and antioxidant activities in vitro.
AB  - Synergistic degradation of water-soluble Auricularia auricula polysaccharide
      (AAP) by solution plasma process (SPP) in the presence of hydrogen peroxide
      (H2O2) was investigated. The effects of H2O2 concentration, AAP concentration and
      the distance between the electrodes on the degradation of AAP were evaluated. The
      results showed that higher H2O2 concentration, lower AAP concentration and
      narrower distance between the electrodes were favorable for the degradation
      effect. Particle size, congo red (CR), scanning electron micrographs (SEM) and
      atomic force microscopy (AFM) results confirmed that SPP irradiation with H2O2
      improved significantly the flexibility of the conformation. The degraded AAPs
      exhibited greater metal chelating effects and DPPH radical scavenging effect than
      the original AAP. It concluded that the combined SPP/ H2O2 method could be used
      for preparation of low-molecular-weight AAP.

PMID- 30093037
TI  - Studies on the binding characteristics of three polysaccharides with different
      molecular weight and flavonoids from corn silk (Maydis stigma).
AB  - Polysaccharides and flavonoids co-existed in corn silk (Maydis stigma) could
      interact inevitably during processing and digestion. In this study, the binding
      interaction between three polysaccharides with different molecular weight and
      flavonoids from corn silk was characterized using molecular dynamic and
      thermodynamic simulation. And the corn silk polysaccharides-flavonoids complex
      (CSP - CSF complex) was characterized using fourier transform infrared (FT-IR)
      spectra, circular dichroism (CD), scanning electron microscope (SEM) and
      differential scanning calorimetry (DSC). The three polysaccharides from corn silk
      showed the molecular weight distributions of 43.3 kDa, 61.3 kDa and 106.6 kDa,
      respectively, and they had the same monosaccharide types with different ratios.
      The adsorption of flavonoids to polysaccharides might be mostly driven by van der
      Waals forces and hydrogen bonding, and it could be described through various
      isothermal models and thermodynamic equations such as Langmuir, Freundlich
      equations and Clausius-Clapeyron equation. This type of interactions could
      improve the biological activities of polysaccharides such as alpha-amylase and
      alpha-glucosidase inhibition.

PMID- 30093038
TI  - Structural characterization and antioxidant activity of water-soluble
      polysaccharides from the Tunisian brown seaweed Cystoseira compressa.
AB  - A fucoidan (CCF) and a sodium alginate (CCSA) were extracted and purified from
      the Tunisian brown seaweed Cystoseira compressa. CCF was a highly sulfated
      heterogalactofucan composed of alpha-(1->3), alpha-(1->4)-linked l-Fucp as main
      backbone which could be highly branched (31.84%) at O-3 and O-4 positions of
      alpha-(1->4)-l-Fucp and alpha-(1->3)-l-Fucp by terminal monosaccharides and side
      chains such as terminal alpha-l-Fucp, terminal beta-d-Galp, beta-d-Galp-(1->3)
      alpha-l-Fucp and beta-d-Galp-(1->4)-alpha-l-Fucp. The ratio of alpha-(1->3)/alpha
      (1->4) linkages was estimated at 3.86:1. CCSA was characterized by HPAEC-PAD,
      GC/MS-EI, ATR-FTIR, and 1H-NMR. The M/G ratio was M/G = 0.77, indicating that
      CCSA respectively contained 44% and 56% of mannuronic and guluronic acids. The
      values of FGG, FMM, FGM (or FMG) blocks as well as the parameter eta were
      estimated. The two polysaccharides exhibited effective antioxidant activities by
      ferrous ion chelation, ferric ion reduction and DPPH radical-scavenging,
      outlining their potentials as natural additives.

PMID- 30093040
TI  - Soybean straw nanocellulose produced by enzymatic or acid treatment as a
      reinforcing filler in soy protein isolate films.
AB  - This work is a comparative study of the application of mercerized soybean straw
      (MSS) and nanocellulose produced by acid (CNCs) or enzymatic hydrolysis (CNFs) as
      reinforcing fillers in soy protein isolate (SPI) films. CNCs presented average
      dimensions of about 10 nm-thick and 300 nm-long with a crystallinity index of
      57%, whereas CNFs have similar diameters, though with greater lengths (>1 MUm),
      lower crystallinity index (50%) and greater thermal stability. Incorporation of
      5% of CNCs and CNFs (g/100 g of SPI) improved the SPI film tensile strength by 38
      and 48% respectively, and decreased the SPI film elongation at break when
      compared to control films. The SPI-CNC films showed the lowest values for
      solubility, probably due to their higher crystallinity (63%). On the other hand,
      the water vapor permeability was solely reduced with CNF addition, which can be
      attributed to their higher aspect ratio (length/diameter) and a better
      incorporation into the protein matrix.

PMID- 30093039
TI  - Comparison of soybean hull pre-treatments to obtain cellulose and chemical
      derivatives: Physical chemistry characterization.
AB  - The cellulose from soybean hull, a waste without value from the argentine
      agriculture, was successfully obtained by using two different treatments: the
      traditional alkaline-bleaching pathway and from a simple pre-alkaline treatment
      at low temperatures. The comparison of both methods yielded similar results
      regarding its ability to open the lignin cellulosic structure of the hull and the
      total elimination of the lignin content. Fourier Transform Infrared spectroscopy
      (FT-IR), Thermogravimetric analysis (TGA), Scanning electron microscopy (SEM),
      13C nuclear magnetic resonance (13C-RMN) and Raman spectroscopy were used to
      characterize the structures and the properties of cellulose. The results showed
      that cellulose can be easily obtained with just an alkaline pre-treatment of 5%
      (w/v) NaOH during 40 h at 50  degrees C and free of any lignin content. The
      attachment of different functional groups, such as -COOH and (CH3)3N+, changed
      the physicochemical properties of the obtained cellulose, showing mayor
      crystalline structure, and consequently modifying the swelling capacity and its
      ability to adsorb model proteins.

PMID- 30093041
TI  - Immune-enhancing activities of chondroitin sulfate in murine macrophage RAW 264.7
      cells.
AB  - As a representative sulfated glycosaminoglycan (GAG), chondroitin sulfate (CS)
      has been reported playing vital roles in the immune response in vivo and in
      vitro. However, limited information is available about their immune-enhancing
      activity. This study was to achieve more precise understandings about the immuno
      stimulating activity of CS. In in vitro experiments, CS was found to
      significantly promote the pinocytic, phagocytic activity and ROS production of
      RAW264.7 cells at the dose range of 100-1000 MUg/mL compared with the untreated
      group (p < 0.05). Further experiments showed that CS could increase the secretion
      levels of NO, TNF-alpha, IL-6 and IL-10 via activating the corresponding mRNA
      expression in macrophages through the toll-like receptor 2 (TLR2). These results
      indicated that CS could function as an immunostimulator to enhance the immune
      responses and might be a potential candidate for application in immunological
      diseases or functional foods.

PMID- 30093042
TI  - Nano-bacterial cellulose/soy protein isolate complex gel as fat substitutes in
      ice cream model.
AB  - The influences of nano-bacterial cellulose (Nano-BC)/soy protein isolate (SPI)
      complex gel on the textural, rheological, and sensory properties of the ice cream
      model were investigated. Nano-BC/SPI mixtures with different ratios (Nano-BC:SPI,
      1:20, 1:15, 1:10, and 1:5 w/w) were prepared with constant total solid content
      (16%). Compared with pure SPI, the thermal stability, textural, rheological and
      emulsifying properties of nano-BC/SPI mixtures were improved. Microstructure of
      nano-BC/SPI complex gels showed that low doses of nano-BC (1:20, 1:15, and 1:10)
      had good compatibility with SPI matrix according to images of confocal laser
      scanning microscopy (CLSM) and scanning electron microscopy (SEM). Nano-BC/SPI
      (1:20) had the most similar textural properties to the cream. When 20% of nano
      BC/SPI (1:20) mixture was added into ice cream as the cream substitute, the
      anticipated ice cream with low calorie, melting resistance, and good textural
      properties was achieved.

PMID- 30093043
TI  - Preparation of micro-nanofibrous chitosan sponges with ternary solvents for dye
      adsorption.
AB  - Chitosan has been widely used to adsorb the contaminants in wastewater owing to
      its unique chemical structure. However, it is difficult to improve its adsorption
      performance by fabricating fibrous chitosan sponge with nanofiber or microfiber
      due to its strong hydrogen bond inside the molecular chain. In this study,
      different from traditional binary acetic acid/water solvents, ternary solvents
      comprised with acetic acid/water/tetrahydrofuran, along with quench temperature
      of -196 C were adopted to prepare three dimensional chitosan sponge with micro
      nanofibrous structure. The chitosan micro-nanofibrous sponge showed substantially
      improved adsorption capacity of Acid Blue-113 (687 mg/g) compared with the
      chitosan sponge (176.5 mg/g) prepared with binary acetic acid/water solvents and
      quench temperature of -20 C. The adsorption of Acid Blue-113 onto chitosan micro
      nanofibrous sponges was a chemical process, which fitted the pseudo-second-order
      and Langmuir isotherm models. The results indicated that microstructure
      modification was an effective and facile way to improve the chitosan adsorption
      capacity. The pure chitosan micro-nanofibrous sponge could be considered as an
      ideal dye adsorbent from wastewater.

PMID- 30093044
TI  - Folate-modified carboxymethyl-chitosan/polyethylenimine/bovine serum albumin
      based complexes for tumor site-specific drug delivery.
AB  - A ternary core/shell based nanoparticulate complex was designed for the
      sequential and site-specific drug delivery. First, bovine serum albumin
      nanoparticles (BSA NPs) were served as the core for loading gambogic acid (GA).
      Subsequently, the BSA NPs were adsorbed by polyethylenimine and then shielded
      with carboxymethyl chitosan-folate (CMCS-FA) as the outer shell for encapsulating
      tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), forming the
      GA/TRAIL co-delivery BSA (GTB) NPs. In normal tissues, the GTB NPs were
      negatively charged; in acidic tumor tissues, the shielding CMCS-FA was detached,
      allowing the release of TRAIL, which binds to the cell death receptor on the
      plasma membrane. The resulting positively charged complex promoted cellular
      internalization and escaped from lysosomes, producing a rapid release of GA,
      which exerted the combined tumor therapy by regulating both intrinsic and
      extrinsic apoptotic pathways. In vitro and in vivo studies confirmed that GTB NPs
      could enhance antitumor efficacy and reduce adverse effects.

PMID- 30093045
TI  - Hygroscopicity modulation of hydrogels based on carboxymethyl chitosan/Alginate
      polyelectrolyte complexes and its application as pH-sensitive delivery system.
AB  - Polyelectrolyte complex (PECs) hydrogels with high hygroscopicity modulation
      ability were successfully prepared based on carboxymethyl chitosan
      (CMCS)/alginate. The swelling ratio of the hydrogels could be tuned from 1 to 450
      simply by changing the weight ratio of CMCS to alginate, and superabsorbent
      hydrogels were obtained when the weight ratio of CMCS to alginate was below 1/1.
      Also, the swelling kinetics and water diffusion mechanism in the hydrogels were
      discussed. In vitro cytotoxicity results indicated that hydrogels had excellent
      cytocompatibility. The swelling ratio of the hydrogel as well as its BSA
      releasing profile was notably pH dependent. Compared with the values at pH 1.2,
      the swelling ratio of hydrogels (CMCS/alginate weight ratio of 1/2) at pH 7.4 was
      about 34 times higher, and the amount of BSA released at pH 7.4 was also
      significantly higher. The as-prepared CMCS/alginate PECs hydrogels hold great
      potential for oral delivery of protein drugs through the intestinal tract.

PMID- 30093046
TI  - Electrospun composite cellulose acetate/iron oxide nanoparticles non-woven
      membranes for magnetic hyperthermia applications.
AB  - In the present work composite membranes were produced by combining magnetic
      nanoparticles (NPs) with cellulose acetate (CA) membranes for magnetic
      hyperthermia applications. The non-woven CA membranes were produced by
      electrospinning technique, and magnetic NPs were incorporated by adsorption at
      fibers surface or by addition to the electrospinning solution. Therefore,
      different designs of composite membranes were obtained. Superparamagnetic NPs
      synthesized by chemical precipitation were stabilized either with oleic acid (OA)
      or dimercaptosuccinic acid (DMSA) to obtain stable suspensions at physiological
      pH. The incorporation of magnetic NP into CA matrix was confirmed by scanning and
      transmission electron microscopy. The results showed that adsorption of magnetic
      NPs at fibers' surface originates composite membranes with higher heating ability
      than those produced by incorporation of magnetic NPs inside the fibers. However,
      adsorption of magnetic NPs at fibers' surface can cause cytotoxicity depending on
      the NPs concentration. Tensile tests demonstrated a reinforcement effect caused
      by the incorporation of magnetic NPs in the non-woven membrane.

PMID- 30093047
TI  - Design of a fermentation process for agave fructooligosaccharides production
      using endo-inulinases produced in situ by Saccharomyces paradoxus.
AB  - Saccharomyces paradoxus, a native microorganism of the aguamiel, was used
      successfully for endoinulinase synthesis for agave fructooligasaccharide (FOS)
      production. We optimized the fermentation parameters to maximize the enzyme
      synthesis, and we performed enzyme kinetics studies to achieve agave fructans
      hydrolysis. The results showed that under constant operating conditions (pH 7.7,
      40  degrees C, 175 rpm of agitation, and 0.005 VVM of aeration) results in the
      production of an enzymatic extract with 49.57 mg/L. This enzymatic extract, when
      mixed with an agave fructans solution containing 37.8 g/L, allowed us to obtain
      products with 18% more FOS content the original concentration. The mass spectrum
      plot shows that the hydrolyzed product contains FOS with a degree of
      polymerization from 5 to 9 hexose units. These results are promising because they
      show FOS production from agave and confirm that importance of using native
      strains in the design of directed fermentation processes.

PMID- 30093049
TI  - Coronary Flow Reserve in the Instantaneous Wave-Free Ratio/Fractional Flow
      Reserve Era: Too Valuable to Be Neglected.

PMID- 30093048
TI  - Prognostic Implication of Thermodilution Coronary Flow Reserve in Patients
      Undergoing Fractional Flow Reserve Measurement.
AB  - OBJECTIVES: This study investigated the prognostic implication of coronary flow
      reserve (CFR) in patients who underwent fractional flow reserve (FFR)
      measurement. BACKGROUND: Limited data are available regarding the long-term
      prognosis associated with thermodilution CFR in patients with coronary artery
      disease. METHODS: A total of 519 patients (737 vessels) who did not undergo
      revascularization were classified according to FFR and CFR values. Low FFR and
      low CFR were defined with upper thresholds of 0.8 and 2.0, respectively. FFR and
      CFR were measured by a pressure-temperature sensor-tipped wire. Clinical outcomes
      were assessed by the vessel-oriented composite outcome (VOCO) (a composite of
      cardiac death, vessel-specific myocardial infarction, and vessel-specific
      revascularization) during 5 years of follow-up. RESULTS: The categorical
      agreement (kappa = 0.080; p = 0.024) between FFR and CFR were modest, and 30.6%
      of the population showed discordant results between FFR and CFR. During 5 years
      of follow-up, patients with low CFR had a significantly higher risk of VOCO than
      did those with high CFR (hazard ratio [HR]: 3.171; 95% CI: 1.664 to 6.042; p <
      0.001). Among patients with high FFR, there were no differences in clinical risk
      factor profiles, FFR, or stenosis severity between the high-CFR and low-CFR
      groups, and low CFR was an independent predictor for VOCO (HR: 4.999; 95% CI:
      2.104 to 11.879; p < 0.001). In a 4-group classification according to both FFR
      and CFR, patients with low FFR and low CFR had the highest risk of VOCO (17.9%;
      overall p < 0.001). CONCLUSIONS: Patients with low CFR had a significantly higher
      risk of clinical events during 5 years of follow-up. Low CFR was an independent
      predictor for patient-oriented composite outcome among patients with high FFR.
      These results support the value of CFR in patients who undergo FFR measurement.
      (Clinical, Physical and Prognostic Implication of Microvascular Status;
      NCT02186093).

PMID- 30093051
TI  - Value of Different Physiological Indexes to Defer Coronary Revascularization.

PMID- 30093052
TI  - New Volumetric Analysis Method for Stent Expansion and its Correlation With Final
      Fractional Flow Reserve and Clinical Outcome: An ILUMIEN I Substudy.
AB  - OBJECTIVES: This study sought to compare conventional methodology (CM) with a
      newly described optical coherence tomography (OCT)-derived volumetric stent
      expansion analysis in terms of fractional flow reserve (FFR)-derived physiology
      and device-oriented composite endpoints (DoCE). BACKGROUND: The analysis of
      coronary stent expansion with intracoronary imaging has used CM that relies on
      the analysis of selected single cross-sections for several decades. The
      introduction of OCT with its ability to perform semiautomated volumetric analysis
      opens opportunities to redefine optimal stent expansion. METHODS: A total of 291
      lesions treated with post-stent OCT and FFR were enrolled. The expansion index
      was calculated by using a novel volumetric algorithm and was defined as: ([actual
      lumen area / ideal lumen area] * 100) for each frame of the stented segment. The
      minimum expansion index (MEI) was defined as the minimum value of expansion index
      along the entire stented segment. MEI and conventional lumen expansion metrics
      were compared for the ability to predict post-stent low FFR (<0.90) and DoCE at 1
      year. RESULTS: There was a stronger correlation between MEI and final FFR,
      compared with CM and final FFR (r = 0.690; p < 0.001) versus (r = 0.165; p =
      0.044). MEI was significantly lower in patients with DoCE than those without DoCE
      (72.18 +/- 8.23% vs. 81.48 +/- 11.03%; p < 0.001), although stent expansion by CM
      was similar between patients with and without DoCE (85.05 +/- 22.19% and 83.73 +/
      17.52%; p = 0.858), respectively. CONCLUSIONS: OCT analysis of stent expansion
      with a newly described volumetric method, but not with CM, yielded data that were
      predictive of both an acute improvement in FFR-derived physiology and DoCE.

PMID- 30093053
TI  - Another Chapter in the Continuing Saga of "Precision Percutaneous Coronary
      Intervention".

PMID- 30093054
TI  - Coronary Psychology: Do You Believe?

PMID- 30093050
TI  - Safety of the Deferral of Coronary Revascularization on the Basis of
      Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable
      Coronary Artery Disease and Acute Coronary Syndromes.
AB  - OBJECTIVES: The aim of this study was to investigate the clinical outcomes of
      patients deferred from coronary revascularization on the basis of instantaneous
      wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable
      angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND: Assessment
      of coronary stenosis severity with pressure guidewires is recommended to
      determine the need for myocardial revascularization. METHODS: The safety of
      deferral of coronary revascularization in the pooled per-protocol population (n =
      4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis
      to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio
      Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute
      Coronary Syndrome) randomized clinical trials was investigated. Patients were
      stratified according to revascularization decision making on the basis of iFR or
      FFR and to clinical presentation (SAP or ACS). The primary endpoint was major
      adverse cardiac events (MACE), defined as the composite of all-cause death,
      nonfatal myocardial infarction, or unplanned revascularization at 1 year.
      RESULTS: Coronary revascularization was deferred in 2,130 patients. Deferral was
      performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in
      the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was
      similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard
      ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical
      presentation with ACS was associated with a higher MACE rate compared with SAP in
      deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted
      hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p =
      0.04). CONCLUSIONS: Overall, deferral of revascularization is equally safe with
      both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently
      deferred when iFR was used to assess physiological significance. In deferred
      patients presenting with ACS, the event rate was significantly increased compared
      with SAP at 1 year.

PMID- 30093055
TI  - Immediate Post-Procedural 12-Lead Electrocardiography as Predictor of Late
      Conduction Defects After Transcatheter Aortic Valve Replacement.
AB  - OBJECTIVES: The aim of this study was to use a 12-lead electrocardiogram obtained
      immediately post-transcatheter aortic valve replacement (TAVR) to identify
      predictors of late high-degree conduction defect (HD-CD) within 30 days after
      TAVR. BACKGROUND: There are limited data on risk factors for the development of
      late HD-CD and the need to retain the temporary pacemaker after TAVR. METHODS: A
      single-center study was conducted including 467 consecutive patients, without pre
      procedural pacemakers, undergoing TAVR. RESULTS: Self-expandable, mechanical, or
      balloon-expandable heart valves were implanted in 328 (70%), 61 (13%), and 78
      (17%) patients, respectively. For patients in sinus rhythm without right bundle
      branch block, late HD-CD developed in 0 of 70 patients (0%; 95% confidence
      interval [CI]: 0% to 5.1%) with PR interval <200 ms and QRS interval <120 ms and
      in 5 of 109 patients (4.6%; 95% CI: 1.5% to 10.4%; all with sufficient escape
      rhythm) with PR interval <240 ms and QRS interval <150 ms. Late HD-CD developed
      in 14 of 101 patients (13.9%; 95% CI: 7.8% to 22.2%; 6 with insufficient escape
      rhythm [5.9%; 95% CI: 2.2% to 12.5%]) with PR interval >=240 ms or QRS interval
      >=150 ms. Furthermore, late HD-CD developed in 3 of 49 patients (6.1%; 95% CI:
      1.3% to 16.9%; all with sufficient escape rhythm) and in 3 of 30 patients (10.0%;
      95% CI: 2.1% to 26.5%; 2 with insufficient escape rhythm [6.7%; 95% CI: 0.8% to
      22.1%]) with atrial fibrillation and no right bundle branch block with QRS
      interval <140 and >=140 ms, respectively. CONCLUSIONS: On the basis of immediate
      post-TAVR 12-lead electrocardiography, removing the temporary pacemaker
      immediately following TAVR is potentially safe in patients without right bundle
      branch block who are: 1) in sinus rhythm with PR interval <240 ms and QRS
      interval <150 ms; or 2) in atrial fibrillation with a QRS interval <140 ms.

PMID- 30093057
TI  - Disarming the Ticking Time Bomb: Post-Procedure Electrocardiography Predictors of
      High-Degree Conduction Disturbances After Transcatheter Aortic Valve Replacement.

PMID- 30093058
TI  - Predicting Futility for Transcatheter Aortic Valve Replacement Procedures: Where
      Do We Stand?

PMID- 30093056
TI  - Predictors of Advanced Conduction Disturbances Requiring a Late (>=48 H)
      Permanent Pacemaker Following Transcatheter Aortic Valve Replacement.
AB  - OBJECTIVES: This study sought to determine predictors of advanced conduction
      disturbances requiring late (>=48 h) permanent pacemaker replacement (PPM) after
      transcatheter aortic valve replacement (TAVR). METHODS: Data of consecutive
      patients were identified by retrospective review of a TAVR database of a single
      center in Milan, Italy, between October 2007 and July 2015. We defined delta PR
      (DeltaPR) and delta QRS (DeltaQRS) interval as the difference between the last PR
      and QRS length available 48 h after TAVR and the baseline PR and QRS length.
      RESULTS: Overall population included 740 patients. We excluded 78 patients who
      already had a PPM and 51 patients who received a PPM <48 h after TAVR. The final
      analysis included 611 patients. Fifty-four patients (8.8%) developed an advanced
      conduction disturbance requiring PPM >=48 h following TAVR. Patients who required
      a late PPM implant had a wider QRS width (113 +/- 25 ms vs. 105 +/- 23 ms; p =
      0.009) and a higher prevalence of baseline right bundle branch block (12.9% vs.
      5.3%; p = 0.026) and were more likely to have a self-expandable valve implanted
      (51.8% vs. 31.9%; p = 0.003). The DeltaPR was 40 +/- 51 ms (p = 0.0001) and the
      DeltaQRS was 22 +/- 61 ms (p = 0.001). Multivariable analysis revealed that
      baseline right bundle branch block (odds ratio: 3.56; 95% confidence interval:
      1.07 to 11.77; p = 0.037) and DeltaPR (odds ratio for each 10-ms increase: 1.31;
      95% confidence interval: 1.18 to 1.45; p = 0.0001) are independent predictors of
      delayed advanced conduction disturbances. CONCLUSIONS: This analysis showed that
      baseline right bundle branch block and the amount of increase of PR length after
      TAVR are independent predictors of late (>=48 h) advanced conduction disturbances
      requiring PPM replacement after TAVR in this cohort. A simple ECG analysis could
      help in detecting potentially lethal advanced conduction disturbances that could
      occur more than 48 h after TAVR.

PMID- 30093059
TI  - Frailty Scales in Transcatheter Aortic Valve Replacement: Incremental Body of
      Evidence.

PMID- 30093060
TI  - Reply: Frailty Scales in Transcatheter Aortic Valve Replacement Incremental Body
      of Evidence.

PMID- 30093061
TI  - In Patients With Atrial Fibrillation Undergoing Percutaneous Coronary
      Intervention, One Size Cannot Fit All.

PMID- 30093062
TI  - Reply: In Patients With Atrial Fibrillation Undergoing Percutaneous Coronary
      Intervention, One Size Cannot Fit All.

PMID- 30093063
TI  - Strong Bias Toward Performing Percutaneous Coronary Intervention in Patients With
      Chronic Total Occlusion Despite Lack of Important Benefit at a Very High Cost and
      Risk to the Patient.

PMID- 30093064
TI  - Reply: Strong Bias Toward Performing Percutaneous Coronary Intervention in
      Patients With Chronic Total Occlusion Despite Lack of Important Benefit at a Very
      High Cost and Risk to the Patient.

PMID- 30093065
TI  - Percutaneous Coronary Intervention Versus Robotic-Assisted Coronary Artery Bypass
      for Left Anterior Descending Artery Chronic Total Occlusion.

PMID- 30093066
TI  - Non-invasive instantaneous wave-free ratio using coronary CT angiography:
      diagnostic performance for evaluation of ischaemia-causing coronary stenosis
      confirmed by invasive fractional flow reserve.
AB  - AIM: To determine the diagnostic performance of instantaneous wave-free ratio
      (iFR) derived from non-invasive coronary computed tomography angiography (CTA;
      iFRCT) for ischaemia-causing coronary stenosis, and to compare the diagnostic
      efficacy of iFRCT, CTA, and CTA plus iFRCT. METHODS AND MATERIALS: Thirty-nine
      patients (55 vessels) with known or suspected coronary artery disease were
      included. All patients underwent invasive coronary angiography and fractional
      flow reserve (FFR) according to CTA findings and clinical indicators. The same
      raw data used for CTA were used to build patient-specific computed flow dynamic
      models and to calculate iFRCT. RESULTS: On a vessel-based level, the correlation
      between iFRCT and FFR was moderate (r=0.65, p<0.05); the optimal iFRCT cut-off
      value was 0.85 based on an FFR cut-off value of 0.80, resulting in 85%
      sensitivity, 69% specificity, 61% positive predictive value (PPV), 89% negative
      predictive value (NPV), and 75% accuracy. The AUC showed significant differences
      between iFRCT and CTA (vessel-based: 0.84 versus 0.68; patient-based: 0.84 versus
      0.62; both p<0.01). The accuracy of CTA combined with iFRCT was significantly
      increased compared to CTA alone for vessels with intermediate stenosis (83%
      versus 40%, p<0.01). CONCLUSION: iFRCT showed better diagnostic performance than
      CTA. iFRCT may be a promising method for detection of ischaemia-causing coronary
      stenosis, even in vessels with intermediate stenosis.

PMID- 30093067
TI  - Multi-scale imaging techniques to investigate solute transport across articular
      cartilage.
AB  - As articular cartilage is an avascular tissue, the transport of nutrients and
      cytokines through the tissue is essential for the health of cells, i.e.
      chondrocytes. Transport of specific contrast agents through cartilage has been
      investigated to elucidate cartilage quality. In laboratory, pre-clinical and
      clinical studies, imaging techniques such as magnetic imaging resonance (MRI),
      computed tomography (CT) and fluorescent microscopy have been widely employed to
      visualize and quantify solute transport in cartilage. Many parameters related to
      the physico-chemical properties of the solute, such as molecular weight, net
      charge and chemical structure, have a profound effect on the transport
      characteristics. Information on the interplay of the solute parameters with the
      imaging-dependent parameters (e.g. resolution, scan and acquisition time) could
      assist in selecting the most optimal imaging systems and data analysis tools in a
      specific experimental set up. Here, we provide a comprehensive review of various
      imaging systems to investigate solute transport properties in articular
      cartilage, by discussing their potentials and limitations. The presented
      information can serve as a guideline for applications in cartilage imaging and
      therapeutics delivery and to improve understanding of the set-up of solute
      transport experiments in articular cartilage.

PMID- 30093070
TI  - Macrophage depletion in cancer therapy: A double-edged sword.

PMID- 30093069
TI  - Corrigendum to 'Comparison of Outcomes of Transfemoral Aortic Valve Implantation
      in Patients <90 to Those >90 Years of Age' [American Journal of Cardiology (2018)
      1581-1586].

PMID- 30093068
TI  - Clinical and Echocardiographic Predictors of Outcomes in Patients With Pulmonary
      Hypertension.
AB  - In pulmonary hypertension (PH), measurement of various echocardiographic
      parameters that assess right heart function is recommended by current clinical
      guidelines. Limited data exists on the combined value of clinical and
      echocardiographic parameters in precapillary PH in the modern era of therapy. We
      examined the association of clinical and echocardiographic parameters with
      surrogate outcomes (6-minute walk distance) and hard outcomes (hospitalization or
      death) in patients with precapillary PH. A cohort of patients with an established
      diagnosis of precapillary PH who underwent transthoracic echocardiography at the
      Duke Echo Lab were prospectively enrolled from 2010 to 2014. Univariable and
      multivariable models were constructed to examine the relation of clinical and
      echocardiographic parameters with surrogate and hard outcomes. Of the 98 patients
      with analyzable echocardiograms with good image quality, 85 were woman, mean age
      was 59.4 years, and 47% had >=World Health Organization functional class III
      symptoms. The mean 6-minute walk distance was 354(+/-132) m, and 83% were on
      pulmonary arterial hypertension medications. At 24 months, the cumulative
      incidence rate for hospitalization or death was 47%. In univariable analyses, the
      REVEAL (Registry to Evaluate Early and Long-term PAH Disease Management) risk
      score (HR 1.72 per 1 SD (2.81) increment, 95% CI 1.34, 2.22; p=<0.001), RV global
      longitudinal strain (RVGLS) (HR 1.54 per 1 SD (5.31) worsening, 95% CI , 2.12;
      p=0.008) and log-2 NT proBNP (HR 1.43 per 1-fold increase, 95% CI 1.25, 1.63;
      p=<0.001) were significantly associated with hospitalization or death.

PMID- 30093071
TI  - Deletion of GARP on mouse regulatory T cells is not sufficient to inhibit the
      growth of transplanted tumors.
AB  - GARP is a transmembrane protein that presents latent TGF-beta1 on the surface of
      regulatory T cells (Tregs). Neutralizing anti-GARP monoclonal antibodies that
      prevent the release of active TGF-beta1, inhibit the immunosuppressive activity
      of human Tregs in vivo. In this study, we investigated the contribution of GARP
      on mouse Tregs to immunosuppression in experimental tumors. Unexpectedly, Foxp3
      conditional garp knockout (KO) mice challenged orthotopically with GL261 tumor
      cells or subcutaneously with MC38 colon carcinoma cells did not show prolonged
      survival or delayed tumor growth. Also, the suppressive function of KO Tregs was
      similar to that of wild type Tregs in the T cell transfer model in allogeneic,
      immunodeficient mice. In conclusion, garp deletion in mouse Tregs is not
      sufficient to impair their immunosuppressive activity in vivo.

PMID- 30093073
TI  - Organic Electronics for Artificial Touch.
AB  - Artificial restoration of touch is an active area of research in
      neuroprosthetics. However, most approaches do not consider emulating the
      biological machinery they intend to replace. Recently, Kim et al. proposed a
      bioinspired artificial touch transducer that closely mimics the behavior of
      natural sensory afferents.

PMID- 30093072
TI  - Evaluation of Structure Indicators for Assessing Skin Cancer Quality of Care in
      Dermatology Departments.
AB  - INTRODUCTION AND OBJECTIVES: A series of quality indicators for melanoma and
      nonmelanoma skin cancer were recently approved within a project promoted by the
      Healthy Skin Foundation of the Spanish AEDV. The aim of this study was to
      evaluate adherence to these indicators. MATERIAL AND METHODS: In November 2016,
      an anonymous questionnaire consisting of 32 items was sent to the heads of
      Spanish dermatology and venereology departments listed in the AEDV's database.
      The questions referred to the above-mentioned quality of care indicators.
      RESULTS: The questionnaire was completed by 104 of the 150 people contacted
      (response rate, 69.3%). The lowest response rate for any given question was 56%
      (84 respondents). Over 85% of respondents answered 29 questions or more (91%).
      The most widely used indicators were those related to the use of computed
      tomography or magnetic resonance imaging for squamous cell carcinoma (98%),
      followed by the availability of a standardized melanoma pathology report (90%).
      The least widely used indicators were related to availability of
      electrochemotherapy (25%) and other invasive therapies for locoregionally
      advanced melanoma (20%). CONCLUSIONS: Adherence to quality of cancer care
      criteria at the different hospitals evaluated varied. Our findings could be
      useful for identifying areas for improvement at different hospitals. Future
      studies should focus on measuring both process and outcome indicators.

PMID- 30093074
TI  - Intervention fidelity in Qigong randomized controlled trials: A method review.
AB  - Intervention fidelity has important implications for the reliability and validity
      of a study. Despite the widely reported health benefits of Qigong exercise
      interventions, the quality of intervention fidelity is less clear. The purpose of
      this paper is to use a valid intervention fidelity assessment tool to evaluate
      how intervention fidelity has been addressed in five areas-design, training,
      delivery, receipt, and enactment-in Qigong randomized controlled studies. A total
      of 86 articles were drawn from CINAHL, PubMed, AMED, and Scopus, and 32 were
      selected for the review. The adherence to intervention fidelity strategies within
      the intervention design, training, delivery, receipt, and enactment was 0.66,
      0.32, 0.22, 0.12, and 0.21, respectively. The findings suggest that intervention
      fidelity is inadequately implemented or reported in published Qigong studies.
      Developing a consistent intervention fidelity plan for Qigong interventions is
      needed. To this aim, we propose a treatment fidelity plan specific to Qigong
      research.

PMID- 30093075
TI  - Older patients' participation in physical activity during hospitalization: A
      qualitative study of ward nurses' perceptions in an Asian context.
AB  - Maximizing the functional ability of older patients through participation in
      physical activities during hospitalization could prevent functional decline. This
      study describes nurses' perceptions of facilitators and barriers to hospitalized
      older patients' physical activity participation in an acute Asian setting. An
      exploratory qualitative study employing thematic analysis was used. Semi
      structured, audio recorded, focus group interviews on 30 nurses from a hospital
      in Singapore, were conducted until data saturation. Facilitators included seeing
      physical activity engagement as a fundamental facet of nursing, drawing social
      contracts and motivating patients, and engaging a multidisciplinary team
      approach. Barriers included psychological factors, falls culture, nurses' heavy
      workload and language impediment. Barriers more unique to the Asian culture were
      patients' adoption of sick-role behavior, reliance on domestic helpers and social
      suppositions on paid service. These findings can be used to develop culturally
      appropriate interventions to promote physical activity participation for patients
      in acute settings in Asia.

PMID- 30093077
TI  - [Key-studies on dupilumab].

PMID- 30093076
TI  - [Contiguous cutaneous inflammation secondary to an aspergillus sinusitis].
AB  - BACKGROUND: Contiguous skin inflammation is a poorly described entity. It
      constitutes a cutaneous manifestation of an underlying ongoing process
      (infectious, inflammatory or neoplastic). Sinusitis is a known cause. PATIENTS
      AND METHODS: We report the case of a 70-year-old patient consulting for an
      ongoing centrofacial inflammatory plaque. Cutaneous biopsy revealed a polymorphic
      inflammatory infiltrate, and cutaneous microbiological specimens were negative. A
      facial CT-scan showed left maxillary sinusitis. Intra-sinus samples obtained at
      surgery showed aspergillus. Voriconazole combined with maxillary sinus surgery
      resulted in healing of the facial plaque. DISCUSSION: There have been only two
      published cases of contiguous skin inflammation related to sinusitis but no
      reported cases caused by aspergillus sinusitis. Herein we report the third case
      of contiguous skin inflammation associated with sinusitis, which is also the
      first related to aspergillus sinusitis.

PMID- 30093078
TI  - [Collodion adult: An uncommon clinical form of caustic dermatitis].

PMID- 30093079
TI  - Numerical prediction of the long-term evolution of acid mine drainage at a waste
      rock pile site remediated with an HDPE-lined cover system.
AB  - Remediation at former mining sites containing waste rock piles (WRPs) commonly
      involves the installation of a cover system over the waste rock to limit water
      and oxygen ingress and attenuate the impacts of acid mine drainage (AMD) to the
      environment. Cover systems containing high-density polyethylene (HDPE) liners
      have the attributes to be highly effective; however, their performance over the
      long-term is unknown. The objective of this study was to assess the long-term
      effectiveness of an 'in-service' HDPE-lined cover system for reducing AMD
      contamination at WRP sites. A numerical investigation of a former mining site
      containing a large WRP reclaimed with an HDPE cover is presented. A 3-D
      groundwater flow and contaminant transport model of the site was developed in
      FEFLOW to predict the spatial and temporal evolution of AMD over 100 years. Field
      parameters observed at 46 monitoring wells over a 5-year monitoring period
      (including hydraulic head, recharge, hydraulic conductivity and water quality)
      were used as key input and calibration parameters. The HDPE cover significantly
      reduced both water recharge to the waste rock (i.e., 512 to 50 mm/year) and AMD
      seepage to groundwater. Both the groundwater flow and contaminant transport
      (sulfate was used as an AMD tracer) components of the model were calibrated and
      verified to the observed field data, with strong correlations evident between
      observed and simulated hydraulic heads and sulfate concentrations, respectively.
      Long-term model predictions of AMD evolution indicated significant and continual
      reductions in sulfate concentrations over time at all well locations. Background
      concentration levels (25 mg/L) are expected to be reached within 40 years. This
      study has demonstrated that HDPE-lined cover systems can be highly effective in
      reducing AMD loading from WRPs and its impacts on the receiving environment.

PMID- 30093081
TI  - JAK-STAT signaling is activated in the kidney and peripheral blood cells of
      patients with focal segmental glomerulosclerosis.
AB  - Focal segmental glomerular sclerosis (FSGS) is a devastating disease with limited
      treatment options and poor prognosis. Activated JAK-STAT signaling has been
      implicated in other kidney diseases. Since new technologies allow us to better
      evaluate changes in systemic and renal JAK-STAT activity as it relates to kidney
      function, we examined this in 106 patients with biopsy-proven FSGS compared to 47
      healthy control individuals. Peripheral immune function was assessed in
      peripheral blood mononuclear cells by phosphoflow studies before and after
      cytokine stimulation. Kidney JAK-STAT activity was measured by immunofluorescence
      and by transcriptomics. A STAT1 activity score was calculated by evaluating
      message status of downstream targets of pSTAT 1. Peripheral blood mononuclear
      cells were found to be upregulated in terms of pSTAT production at baseline in
      FSGS and to have limited reserve to respond to various cytokines. Increased
      staining for components of the JAK-STAT system in FSGS by microscopy was found.
      Furthermore, we found transcriptomic evidence for activation of JAK-STAT that
      increased pSTAT 1 and pSTAT 3 in glomerular and tubulointerstitial sections of
      the kidney. Some of these changes were associated with the likelihood of
      remission of proteinuria and progression of disease. JAK-STAT signaling is
      altered in patients with FSGS as compared to healthy controls with activated
      peripheral immune cells, increased message in the kidney and increased activated
      proteins in the kidney. Thus, our findings support immune activation in this
      disease and point to the JAK-STAT pathway as a potential target for treatment of
      FSGS.

PMID- 30093083
TI  - Influence of cross-linkers on ezrin-bound minimal actin cortices.
AB  - The actin cortex is a thin network coupled to the plasma membrane of cells,
      responsible for e.g., cell shape, motility, growth and division. Several model
      systems for minimal actin cortices (MACs) have been discussed in literature
      trying to mimic the complex interplay of membrane and actin. We recapitulate on
      different types of MACs using either three dimensional droplet interfaces or
      lipid bilayers to which F-actin networks are attached to or planar lipid bilayers
      with bound actin networks. Binding of the network to the membrane interface
      significantly influences its properties as well as its dynamics. This in turn
      also influences, how cross-linkers as well as myosin motors act on the network.
      Here, we describe the coupling of a filamentous actin network to a model membrane
      via the protein ezrin, a member of the ezrin-radixin-moesin family, which forms a
      direct linkage between the plasma membrane and the cortical web. Ezrin binding to
      the membrane is achieved by the lipid PtdIns(4,5)P2, while attachment to F-actin
      is mediated via the C-terminal domain of the protein leading to a two dimensional
      arrangement of actin filaments on the membrane. Addition of cross-linkers such as
      fascin and alpha-actinin influences the architecture of the actin network, which
      we have investigated by means of fluorescence microscopy. The results are
      discussed in terms of the dynamics of the filaments on the membrane surface.

PMID- 30093080
TI  - Targeted inhibition of the type 2 cannabinoid receptor is a novel approach to
      reduce renal fibrosis.
AB  - The cannabinoid receptor type 2 (CB2) is a G protein-coupled seven transmembrane
      receptor that transmits endogenous cannabinoid signaling. The role of CB2 in the
      pathogenesis of kidney injury and fibrosis remains poorly understood. Here we
      demonstrate that CB2 was induced, predominantly in kidney tubular epithelium, in
      various models of kidney disease induced by unilateral ureteral obstruction,
      adriamycin or ischemia/reperfusion injury. In vitro, forced expression of CB2 or
      treatment with a CB2 agonist was sufficient to trigger matrix gene expression,
      whereas knockdown of CB2 by siRNA abolished transforming growth factor-beta1
      induced signaling and fibrogenic responses in kidney tubular cells. CB2 also
      mediated fibroblasts and macrophage activation in vitro. Mice with genetic
      ablation of CB2 were protected against kidney injury after ureteral obstruction,
      validating a pathogenic role of CB2 in renal fibrosis in vivo. By using in silico
      screening and medicinal chemistry modifications, we discovered a novel compound,
      XL-001, that bound to CB2 with high affinity and selectivity and acted as an
      inverse agonist. Incubation with XL-001 inhibited in a dose-dependent fashion the
      fibrogenic response induced by CB2 overexpression, CB2 agonist or transforming
      growth factor-beta1. In vivo, intraperitoneal injections of XL-001 ameliorated
      kidney injury, fibrosis and inflammation in both the obstruction and
      ischemia/reperfusion models. Delayed administration of XL-001 was also effective
      in ameliorating kidney fibrosis and inflammation. Thus, CB2 is a pathogenic
      mediator in kidney fibrosis and targeted inhibition with the novel inverse
      agonist XL-001 may provide a strategy in the fight against fibrotic kidney
      diseases.

PMID- 30093082
TI  - Implementation of a politically initiated national clinical guideline for cardiac
      rehabilitation in hospitals and municipalities in Denmark.
AB  - A politically initiated national clinical guideline was launched in Denmark in
      2013 to improve quality and equality of cardiac rehabilitation (CR) services. The
      guideline is to be implemented in both hospital and community (municipality)
      settings due to shared responsibility for provision of CR services. Little is
      known about implementation outcomes of a guideline in these two settings. We
      aimed to study this by determining the extent to which Danish CR services in
      hospitals and municipalities adhered to national recommendations following the
      launch of the guideline. The study employed an observational, longitudinal
      design. Data were gathered by a questionnaire survey to compare CR services at
      baseline, measured in 2013 immediately before the guideline was launched, with CR
      services at a two-year follow up in 2015. All Danish hospital departments
      offering CR services (N = 36) and all municipalities (N = 98) were included. Data
      were analysed using inferential statistics. Hospitals reported improvement of
      both content and quality of CR services. Municipalities reported no change in
      content of services, and lower level of fulfilment of one quality aspect. The
      results suggest that the guideline had different impact in hospitals and
      municipalities and that the differences in content and quality of services
      between the two settings increased in the study period, thus contradicting the
      guideline's aim of uniform, evidence-based content of CR services across
      settings.

PMID- 30093085
TI  - Antioxidant effects on the intracerebroventricular galactose damage in rats.
AB  - We investigated the effects of the intracerebroventricular infusion of galactose
      and the influence of pretreatment with antioxidants on oxidative stress
      parameters and acethylcholinesterase (AChE) activity in the brain of 60-day-old
      Wistar rats (6 per group). The animals were divided into naive group (did not
      undergo surgery); procedure group (only underwent surgery); sham group (underwent
      surgery and received 5 MUL saline) and galactose group (received 5 MUL of
      galactose solution (5.0 mM) by intracerebroventricular injection), and were
      killed by decapitation after 1 h. Other groups were pretreated daily for 1 week
      with saline (sham and galactose groups) or antioxidants, alpha-tocopherol (40
      mg/kg) plus ascorbic acid (100 mg/kg, i.p.) (antioxidants and galactose +
      antioxidants groups). Twelve hours after the last antioxidants injection, animals
      received an intracerebroventricular infusion of 5 MUL of galactose solution
      (galactose and galactose + antioxidants groups) or saline (sham and antioxidants
      groups) and were sacrificed 1 h later. Galactose elevated thiobarbituric acid
      reactive substances (TBA-RS), protein carbonyl content and glutathione peroxidase
      (GSH-Px) activity and decreased total sulfhydryl content and catalase (CAT)
      activity in the cerebral cortex. In the hippocampus, galactose enhanced TBA-RS,
      decreased total sulfhydryl content and increased AChE activity, while in the
      cerebellum it decreased total sulfhydryl content and increased CAT and superoxide
      dismutase (SOD) activities. Pretreatment with antioxidants prevented the majority
      of these alterations, indicating the participation of free radicals in these
      effects. Thus, intracerebroventricular galactose infusion impairs redox
      homeostasis in the brain; the administration of antioxidants should be considered
      as an adjuvant therapy to specific diets in galactosemia.

PMID- 30093086
TI  - Juvenile nasopharyngeal angiofibroma surgical treatment in paediatric patients.
AB  - INTRODUCTION AND OBJECTIVES: The juvenile nasopharyngeal angiofibroma is a highly
      vascularised benign neoplasm of complex treatment in its surgical preparation,
      surgery to be performed, risks and recurrences. The aim of the study was to
      analyze the management and surgical treatment for the pathology of juvenile
      nasoangiofibroma. MATERIALS AND METHODS: We reviewed the clinical histories and
      images of the patients who underwent surgery with a pathology result of juvenile
      nasoangiofibroma in the period from January 2008 to December 2016. RESULTS: Sixty
      one cases were treated; all of them treated using the same surgical access by
      means of a Le Fort I osteotomy. All of the patients were male, with an average
      age of 13.3 years. The Andrew-Fish classification was used for staging the cases,
      most were staged as grade II and I. CONCLUSIONS: The described approach provided
      extensive surgical access, which was adequate for the different stages of the
      tumour. It requires experience to be able to resect the tumour with the least
      possible bleeding.

PMID- 30093087
TI  - Update on consensus on diagnosis and treatment of idiopathic sudden sensorineural
      hearing loss.
AB  - INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a sudden,
      unexplained unilateral hearing loss. OBJECTIVES: To update the Spanish Consensus
      on the diagnosis, treatment and follow-up of ISSNHL. MATERIAL AND METHODS: After
      a systematic review of the literature from 1966 to March 2018, on MESH terms
      "(acute or sudden) hearing loss or deafness", a third update was performed,
      including 1508 relevant papers. RESULTS: Regarding diagnosis, 11ISSNHL is
      clinically suspected, the following diagnostic tests are mandatory: otoscopy,
      acumetry, tonal audiometry, speech audiometry, and tympanometry, to discount
      conductive causes. After clinical diagnosis has been established, and before
      treatment is started, a full analysis should be performed. An MRI should then be
      requested, ideally performed during the first 15 days after diagnosis, to
      discount specific causes and to help to understand the physiopathological
      mechanisms in each case. Although treatment is very controversial, due to its
      effect on quality of life after ISSNHL and the few rare adverse effects
      associated with short-term steroid treatment, this consensus recommends that all
      patients should be treated with steroids, orally and/or intratympanically,
      depending on each patient. In the event of failure of systemic steroids,
      intratympanic rescue is also recommended. Follow-up should be at day 7, and after
      12 months. CONCLUSION: By consensus, results after treatment should be reported
      as absolute decibels recovered in pure tonal audiometry and as improvement in
      speech audiometry.

PMID- 30093084
TI  - Impact of biological agents on the prevalence of chemotherapy associated liver
      injury (CALI): Multicentric study of patients operated for colorectal liver
      metastases.
AB  - BACKGROUND: The prevalence of chemotherapy associated liver injuries (CALI),
      especially SOS (sinusoidal obstruction syndrome) and NRH (nodular regenerative
      hyperplasia) might be reduced since the introduction of routine use of biological
      agents with chemotherapy in colorectal liver metastases (CRLM). METHODS: One
      hundred patients with CRLM having undergone at least one liver segment resection
      were prospectively included, and chemotherapy data recorded. Specimens were
      reviewed by a single pathologist and CALI were described. Prevalence of CALI was
      compared to our previous experience published in 2013. NRH diagnosis was
      performed on reticulin special stain, by contrast to our previous study.
      Postoperative outcome was analysed. RESULTS: Bevacizumab was more frequently
      administrated in patients of the present study: 53/100 (53%) compared to 20/151
      (13%), p < 0.0001. Overall, in the present series, SOS was only observed in
      28/100 (28%) patients compared to 116/151 (77%) in 2013 (p < 0.001). When looking
      specifically to patients receiving Bevacizumab with Folfox, we observed a reduced
      SOS prevalence compared to Folfox alone (p = 0.008). A higher prevalence of NRH
      was found in the present study, related to increased detection accuracy, but in
      patients receiving Bevacizumab in association with Folfox, this prevalence was
      also reduced compared to Folfox alone (p = 0.03). Both SOS and NRH were
      associated with severe complications (p = 0.008 and p = 0.005, respectively) and
      postoperative liver insufficiency (p < 0.001 and p < 0.01, respectively).
      CONCLUSIONS: The routine use of Bevacizumab in association with Folfox
      significantly reduced CALI prevalence, in turn linked to severe postoperative
      complications.

PMID- 30093088
TI  - Efficacy of intratympanic corticosteroid as a salvage treatment in idiopathic
      sudden sensorineural hearing loss.
AB  - INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as
      an abrupt hearing loss of at least 30dB of unknown cause. The hearing response
      obtained after intratympanic steroid injection as a salvage treatment after a
      prior failure of initial systemic steroid treatment was analysed. MATERIAL AND
      METHOD: An observational study was performed on 125 cases of ISSHL who were
      diagnosed from 2006 to 2014. Sixteen achieved complete recovery after one week
      according to Siegel's criteria. The remaining 109 cases were analysed in two
      groups: one that received intratympanic corticosteroid salvage therapy (treatment
      group) and one that did not (control group). The recovery was analysed after 6
      months and 2 years of follow-up. RESULTS: The difference between each group at
      baseline were not statistically significant. After systemic treatment for 7 days,
      PTA in the control group was 53.13dB and 66.11dB in the treatment group (P<.01).
      After 6 months, the mean PTA improvement was 10.84dB in the treatment group, and
      1.13dB in the control group, a significant difference (P<.0001). Only 10 cases
      achieved full hearing recovery after intratympanic corticosteroid salvage
      therapy, none of the patients did so in the control group. CONCLUSION:
      Intratympanic corticosteroid rescue for ISSHL acheived hearing improvement for
      the cases with failure of initial systemic corticosteroid treatment. However,
      this treatment did not provide complete hearing recovery according to Siegel's
      criteria in most cases.

PMID- 30093089
TI  - Assessing the domino effect: Female physician industry payments fall short,
      parallel gender inequalities in medicine.
AB  - BACKGROUND: Physician-industry relationships have been complex in modern
      medicine. Since large proportions of research, education and consulting are
      industry-backed, this is an important area to consider when examining gender
      inequality in medicine. METHODS: The Open Payments Program (OPP) database from
      August 2013 to December 2016 was analyzed. In order to identify physicians'
      genders, the OPP was matched with the National Provider Index dataset.
      Descriptive statistics of payments to female compared to male surgeons were
      obtained and stratified by payment type, subspecialty, geographic location and
      year. RESULTS: 3,925,707 transactions to 136,845 physicians were analyzed. Of
      them, 31,297 physicians were surgeons with an average payment per provider of
      $131,252 to male surgeons compared to $62,101 to female surgeons. Significantly
      fewer women received consultant, royalty/licensure, ownership and speaker
      payments. However, women received a higher average amount per surgeon compared to
      their male counterparts within research payments. Overall payments to women
      trended upwards over time. CONCLUSION: Gender inequality still exists in
      medicine, and in industry-physician payments. Industry should increasingly
      consider engaging women in consultancies, speaking engagements, and research.

PMID- 30093090
TI  - Optimizing adjuvant endocrine therapy for early ER+ breast cancer: An update for
      surgeons.
AB  - INTRODUCTION: The optimal duration of adjuvant endocrine therapy in early ER +
      breast cancer has been controversial. This article aims to provide an overview of
      the evidence. METHODS: A search of the literature was conducted via MEDLINE using
      appropriate keywords. Eligible studies were screened and relevant articles were
      selected for this report. RESULTS: Studies investigating the role of extended
      adjuvant tamoxifen beyond 5 years have revealed mixed results depending on the
      proportion of node positivity. In postmenopausal women, aromatase inhibitors
      (AIs) for 5 years are superior to tamoxifen. Extending the use of AIs beyond 5
      years seem to reduce the risk of relapse in postmenopausal women with node
      positive disease. The addition of bisphosphonates to counteract AI-related
      osteopenia may further improve overall and disease-free survival. Women younger
      than 40 years seem to benefit from ovarian suppression combined with tamoxifen or
      exemestane. CONCLUSIONS: An individualised approach is required for every
      patient. The adverse effects of endocrine therapy should be weighed against the
      potential benefits of extended therapy to better inform decision-making.

PMID- 30093092
TI  - The value of psychometric analysis of the advanced trauma life support cognitive
      test: Outcome of an ACS-Accredited educational institute multisite study.
AB  - BACKGROUND: The Advanced Trauma Life Support(r) (ATLS(r)) course provides a
      standard approach to trauma. Participants must pass the ATLS(r) post-test. We
      deployed the test online to allow ongoing psychometric item analysis and
      potential objective refinement. METHODS: A two-phase study was undertaken with
      the ACS COT permission. In the first phase, ATLS(r) post-test #2 was computerized
      and deployed using Qualtrics(c). Data were collected from fourteen courses
      conducted between 2014 and 2015 (n = 306) at one ACS AEI site. In the second
      phase, the same post-test was administered to 238 trainees in 10 courses via
      secured computers at four ACS AEI sites in 2016. RESULTS: Phase 1 item analyses
      showed two items with very low percentages correct, and one of these also showed
      a low discrimination index. Phase 2 item analyses suggested four items as
      candidates for review and possible revision. We also found differences by learner
      background and by instructional site. CONCLUSIONS: This study demonstrates
      computerized delivery of the ATLS post-test is feasible, promotes psychometric
      analysis, and could improve the quality of the test. Further collaboration
      between the ACS COT and ACS AEI would be beneficial.

PMID- 30093091
TI  - Are we meeting ACGME core competencies? A systematic review of literature on
      international surgical rotations.
AB  - BACKGROUND: In response to the growing interest in global surgery among trainees,
      international surgical rotation (ISR) was approved as a formal elective of
      resident curriculum. To define ISR's role, we aim to identify the six core
      competencies of Accreditation Council for Graduate Medical Education (ACGME) in
      individual institution's experience. DATA SOURCES: This is a systematic
      literature review studying general surgery resident experience in ISR as it
      pertains to the ACGME core competencies. Articles were searched using PubMed,
      Scopus, and Web of Science. Each abstract and article was reviewed, selected, and
      tabulated. CONCLUSION: Fourteen articles were selected for the review after
      inclusion and exclusion criteria were applied. We found that ISR provided a
      valuable educational experience for US surgical residents by meeting the ACGME
      core competencies in a different environment. ISR is an important addition to the
      general surgery curriculum. Future direction should focus on bidirectional ISR
      and educational consortium development.

PMID- 30093093
TI  - A study of the visual symptoms in two-dimensional versus three-dimensional
      laparoscopy.
AB  - AIM: There are reports of visual strains and associated symptoms when operating
      in a 3D laparoscopic environment. We aimed to study the extent of visual symptoms
      seen in 3D versus conventional 2D imaging in volunteers performing laparoscopic
      tasks and study the effect of eye exercises on 3D laparoscopy. METHODS: Twenty
      four consented laparoscopic novices were required to undergo a visual acuity test
      (Snellen chart) and eye deviation test (Maddox Wing). A battery of specific
      isolated laparoscopic tasks lasting 30 min was developed to test their ability to
      detect changes in 2D and 3D environments separately. Before and after the 2D and
      3D laparoscopic tasks, subjects were asked to complete a standardised
      questionnaire designed to scale (from 0 to 10) their visual symptoms (blurred
      vision, difficulty in refocusing from one distance to another, irritated or
      burning eyes, dry eyes, eyestrain, headache and dizziness). Participants who
      underwent 3D laparoscopic tasks were randomized into two groups, those who
      received two minutes eye exercises before performing the tasks and those who
      didn't. Independent t-test was used for the statistical analysis of this study.
      RESULTS: Visual symptoms and eye strain were significant in 2D (p < 0.01) and
      difficulty in refocusing from one distance to another was significant in 3D
      laparoscopic imaging (p < 0.05). There was no significant effect of the simple
      eye exercises on relieving the visual symptoms in the 3D group. CONCLUSION:
      Visual symptoms were present in both 2D and 3D imaging laparoscopy. Eye strain
      was prominent in 2D imaging, while difficulty in refocusing from one distance to
      another was prominent in 3D. Eye exercises for 3D visual symptoms did not bring
      any significant improvement.

PMID- 30093094
TI  - Providing hyper-branched dendrimer conjugated with beta-cyclodextrin based on
      magnetic nanoparticles for the separation of methylprednisolone acetate.
AB  - This study introduced a developed approach for dendritic beta-cyclodextrin (beta
      CD) in order to obtain high sorption capacity. Synthetic strategy exploits the
      reactivity between acrylic acid and allyl glycidyl ether for high-yielding
      assembly via grafting on to the magnetic nanoparticles that are modified using 3
      mercaptopropyltrimethoxysilane for various building branches and host-guest
      molecules of beta-CD. The methodology has been applied for the preparation of a
      series of beta-CD conjugated magnetic nanoparticles with dendrimers as a nano
      sorbent for the extraction of methylprednisolone acetate. This study allowed us
      to probe (i) the effects of the dendric-cyclodextrin architecture on the affinity
      of sorption capacity, (ii) the drug influence between the cyclodextrin core and
      the polyester dendrimer, and (iii) the result of sorbent formation for using the
      anti-inflammatory drug as a target guest into the ring of beta-CD on biological
      extraction. It was found that the adsorption behavior could be fitted by the
      Langmuir adsorption isotherm model. The adsorption capacity of MPA is found to be
      12.4 mg g-1 and indicated the homogeneous sites onto polymer grafted magnetite
      nano-sorbent surface. Our results confirm the high capability of this type of
      dendrimer-beta-CD for drug extraction in biological fluids and pharmaceutical
      samples. This nano-sorbent assists the magnetic solid phase extraction technique
      represented in the high extraction yield (up to 97%) for methylprednisolone
      acetate in biological human fluids and pharmaceutical samples. Moreover, the
      achieved polymeric nano-sorbent of the reaction combination was facilitated by a
      magnetic field and reusability was performed without any notable loss in the
      sorbent activity.

PMID- 30093095
TI  - Separation of terbutaline enantiomers in capillary electrophoresis with
      cyclodextrin-type chiral selectors and investigation of structure of selector
      selectand complexes.
AB  - The affinity pattern of terbutaline enantiomers towards various cyclodextrins was
      studied using capillary electrophoresis. The affinity pattern of terbutaline
      enantiomers was the same towards all studied cyclodextrins except heptakis(2-O
      methyl-3,6-di-O-sulfo)-beta-CD. Nuclear magnetic resonance spectroscopy was used
      for understanding of fine structural mechanisms of interactions of beta
      cyclodextrin and its two sulfated derivatives with the enantiomers of
      terbutaline. The structure of terbutaline complexes with all 3 cyclodextrins
      studied was different from each other. In confirmation with our earlier studies
      it was shown again that capillary electrophoresis represents very sensitive
      technique for studies of affinity patterns in cyclodextrin complexes with chiral
      guests. Other instrumental (e.g. NMR spectroscopy and X-ray diffraction analysis)
      and theoretical techniques, although very useful for obtaining the information
      regarding the stoichiometry, binding constants and structure of intermolecular
      complexes, as well as about the forces involved in selector-selectand binding and
      chiral recognition, may sometimes fail to properly sense those fine differences
      in the affinity patterns. Therefore, it is recommended to use capillary
      electrophoresis in order to examine correctness of affinity pattern determined
      for intermolecular complexes of cyclodextrins with guest molecules by other
      instrumental or computation techniques.

PMID- 30093096
TI  - Influence of organic modifier and separation modes for lipophilicity assessment
      of drugs using thin layer chromatography indices.
AB  - Lipophilicity constitutes one of the most important physicochemical properties in
      the design and development of drug molecules. In the present work thin layer
      chromatography (TLC) has been utilized to evaluate lipophilicity of 11
      representative drugs, which included six proton pump inhibitors (omeprazole,
      pantoprazole, rabeprazole, lansoprazole, ilaprazole, and tenatoprazole), an anti
      vertigo drug, betahistine, nonsteroidal anti-inflammatory drug, ibuprofen, anti
      malarial drug, atovaquone, an anti-HIV agent, atazanavir and a hormonal drug,
      calcitriol. Normal as well as reversed-phase separation modes were evaluated to
      study the effect of different organic modifiers for the estimation of
      lipophilicity. The quantitative descriptor of lipophilicity, the partition
      coefficient (logP) was estimated by suitably optimizing the solvent systems for
      both the modes. The best mobile phase pairs for NPTLC and RPTLC were toluene
      acetonitrile and water-methanol respectively. Principal component analysis,
      hierarchical cluster analysis, as well as non-parametric methods like sum of
      ranking differences and generalized pair wise correlation revealed the dominant
      pattern in the data. The results obtained from both the separation modes were
      comparable and were in good agreement with the computational data for all the
      drugs.

PMID- 30093098
TI  - Incidence of surgical site infection and risk factors in rectal surgery: A
      prospective cohort study.
AB  - INTRODUCTION: Surgical site infection (SSI) is the main cause of nosocomial
      infection in Spain. The aim of this study was to analyze the incidence of SSI and
      to evaluate its risk factors in patients undergoing rectal surgery. METHODS:
      Prospective cohort study, conducted from January 2013 to December 2016. Patient,
      surgical intervention and infection variables were collected. Infection rate was
      calculated after a maximum period of 30 days of incubation. The effect of
      different risk factors on infection was assessed using the odds ratio adjusted by
      a logistic regression model. RESULTS: The study included 154 patients, with a
      mean age of 69.5+/-12 years. The most common comorbidities were diabetes mellitus
      (24.5%), chronic obstructive pulmonary disease (17%) and obesity (12.6%). The
      overall incidence of SSI during the follow-up period was 11.9% (CI95%: 7.8-17.9)
      and the most frequent microorganism was Escherichia coli (57.9%). Risk factors
      associated with surgical wound infection in the univariate analysis were blood
      transfusion, drain tubes and vasoactive drug administration (P<.05). CONCLUSIONS:
      The incidence of SSI in rectal surgery was low. It is crucial to assess SSI
      incidence rates and to identify possible risk factors for infection. We recommend
      implementing surveillance and hospital control programs.

PMID- 30093099
TI  - Use of social networks by general surgeons. Results of the national survey of the
      Spanish Association of Surgeons.
AB  - INTRODUCTION: The use and utility of social media (SM) among Spanish general
      surgeons is unknown. METHODS: Between October and December 2017 an online survey
      was carried out to the members of the Spanish Association of Surgeons, in which
      data on the profile of use and opinion on the usefulness of SM were collected.
      RESULTS: 360 valid responses were obtained, 310 from surgeons who had an active
      SM profile. The most popular networks were: Facebook (86%), LinkedIn (61,6%),
      YouTube (60,6%) and Twitter (54,2%). LinkedIn and Twitter stood out as the most
      used SM for professional purposes. Surgeons with a SM profile were younger
      (42.4+/-11 years versus 51.6+/-8 years; P<.001). Gender did not show influence on
      presence in SM. The majority of respondents have profiles in more than one
      network (3.6+/-1 accounts) and 73.5% reported daily access to them; 19.7% of the
      surgery departments to which the respondents belong have a SM account. Among SM
      utilities in the professional field, training activities (87%) and connectivity
      among professionals (84%) were the most outstanding; 14.1% of respondents use SM
      to interact with patients. CONCLUSIONS: SM is useful as a tool for the
      acquisition, updating and dissemination of scientific knowledge, also proving
      valuable as a new form of interaction among surgeons. Other issues such as
      privacy or surgeon-patient relationship represent a barrier to its use.

PMID- 30093100
TI  - Liver transplantation from type II donation after cardiac death donor with
      normothermic regional perfusion and normothermic machine perfusion.
AB  - BACKGROUND: The current imbalance between donor supply and patients on the
      waiting list for liver transplantation (LT) is significant. To resolve this
      situation, marginal organs, such as those from type 2 donation after cardiac
      death (DCD2), are being considered. METHODS: In the present article, we present
      the first LT with a new protocol consisting in normothermic regional perfusion
      (NRP) and normothermic machine perfusion (NMP) for a type 2 DCD graft initially
      rejected for LT. RESULTS: After a favorable evolution with NMP (improved
      macroscopic appearance of the graft, acid-base equilibrium control and bile
      production), the transplantation was performed without major incidents. The
      evolution of the graft and patient were favorable. After 3 months,
      cholangiography showed no signs of ischemic cholangiopathy. CONCLUSIONS: Three
      month patient and graft survival are encouraging, but more cases are needed to
      test the clinical efficacy of the new protocol.

PMID- 30093102
TI  - Hybrid algorithmic approach oriented to incipient rotor fault diagnosis on
      induction motors.
AB  - This paper investigates the current monitoring for effective fault diagnosis in
      induction motor (IM) by using random forest (RF) algorithms. A rotor bar breakage
      of IM does not derive in a catastrophic fault but its timely detection can avoid
      catastrophic consequences in the stator or prevent malfunctioning of those
      applications in which this sort of fault is the primary concern. Current-based
      fault signatures depend enormously on the IM power source and in the load
      connected to the motor. Hence, homogeneous sets of current signals were acquired
      through multiple experiments at particular loading torques and IM feedings from
      an experimental test bench in which incipient rotor severities were considered.
      Understanding the importance of each fault signature in relation to its diagnosis
      performance is an interesting matter. To this end, we propose a hybrid approach
      based on Simulated Annealing algorithm to conduct a global search over the
      computed feature set for feature selection purposes, which reduce the
      computational requirements of the diagnosis tool. Then, a novel Oblique RF
      classifier is used to build multivariate trees, which explicitly learn optimal
      split directions at internal nodes through penalized Ridge regression. This
      algorithm has been compared with other state-of-the-art classifiers through
      careful evaluation of performance measures not encountered in this field.

PMID- 30093101
TI  - Robust fuzzy tracking control of a quad-rotor unmanned aerial vehicle based on
      sector linearization and interval matrix approaches.
AB  - In this paper, the robust Hinfinity fuzzy tracking control strategy for a quad
      rotor unmanned aerial vehicle (UAV) with strong coupling and highly nonlinear is
      put forward based on the Takagi-Sugeno(T-S) fuzzy error model. Firstly, the quad
      rotor UAV system is divided into altitude subsystem, position subsystem and
      attitude subsystem. Through selecting appropriate premise variables, three T-S
      fuzzy error models, which are equivalent to the error dynamic model, are
      established by the sector linearization approach. Next, the uncertainties in drag
      coefficients, moments of inertia are taken into account, and the interval matrix
      is introduced to describe them in altitude, position and attitude T-S fuzzy error
      models. Then the robust Hinfinity fuzzy feedback controllers are designed to
      stabilize T-S fuzzy subsystems. Besides, according to the Lyapunov stability
      theorem, it is obtained that the LMI sufficient conditions of exponential
      stability with the prescribed Hinfinity performance for T-S fuzzy closed-loop
      subsystems. Meanwhile, the method for solving the gain matrices of controller is
      presented. Finally, simulation results are given to demonstrate the
      effectiveness, robustness and advantages of the proposed method. Then the
      feasibility of the proposed method is further verified by experimental results.

PMID- 30093097
TI  - The Spindle: Integrating Architecture and Mechanics across Scales.
AB  - The spindle segregates chromosomes at cell division, and its task is a mechanical
      one. While we have a nearly complete list of spindle components, how their
      molecular-scale mechanics give rise to cellular-scale spindle architecture,
      mechanics, and function is not yet clear. Recent in vitro and in vivo
      measurements bring new levels of molecular and physical control and shed light on
      this question. Highlighting recent findings and open questions, we introduce the
      molecular force generators of the spindle, and discuss how they organize
      microtubules into diverse architectural modules and give rise to the emergent
      mechanics of the mammalian spindle. Throughout, we emphasize the breadth of space
      and time scales at play, and the feedback between spindle architecture, dynamics,
      and mechanics that drives robust function.

PMID- 30093103
TI  - A solution for enhancement of transient performance in nonlinear adaptive
      control: Optimal adaptive reset based on barrier Lyapunov function.
AB  - In this paper, an adaptive controller based on barrier Lyapunov function combined
      with an optimal reset rule is devised in order to improve the transient
      performance of nonlinear adaptive control. A novel reset rule is designed such
      that the estimated parameters of the adaptive controller jump to the optimal
      values in a way that optimizes a cost function representing the transient
      performance index. It is proved that asymptotic tracking is achieved and the
      output remains in a desired bound by ensuring boundedness of the barrier Lyapunov
      function. Besides, the convergence rate is increased by resetting the estimated
      parameters to optimal values. A regularly referred example is simulated to
      demonstrate the effectiveness of the proposed method and the results are compared
      with the existing investigations.

PMID- 30093104
TI  - Novel approach using Hilbert Transform for multiple broken rotor bars fault
      location detection for three phase induction motor.
AB  - This paper presents a new approach to detect the location of multiple broken
      rotor bars (MBRBs) in induction motor (IM) drive, running under no load and full
      load conditions using direct in and variable frequency drives. This technique is
      based on earlier work of location detection of one broken rotor bar. The
      techniques are tested for various fault severity levels so the detection of the
      exact location of the fault at early stage helps to reach sufficient time
      maintenance. In this paper, the authors used Hilbert Transform to extract the
      fault signature from the stator current envelope which is the low frequency
      component. Then statistical analysis is applied which produce a formula that is
      used to get the exact location of the fault in IM rotor.

PMID- 30093105
TI  - Discrete-time setpoint-triggered reset integrator design with guaranteed
      performance and stability.
AB  - According to Bode's gain-phase relationship, in linear time-invariant
      controllers, introducing an integral action to eliminate the steady-state error
      has an adverse effect of increased phase delay and overshoot, leading to
      performance deterioration. Moreover, increasing the bandwidth of the closed-loop
      system to enhance the low-frequency disturbance rejection invariably amplifies
      the sensitivity to high-frequency disturbances. Hence, the performance of the
      linear controllers is always limited due to these fundamental frequency- and time
      domain limitations. Motivated by the desire to address the fundamental
      limitations of linear controllers and improve the time-varying closed-loop
      performance, we put forward a novel setpoint-triggered reset integrator strategy
      that varies the integrator cut-off frequency based on the setpoint information.
      Particularly, to tackle the time-varying disturbances and setpoint profiles, the
      proposed controller consists of a nominal linear controller and a variable-gain
      reset integrator. We show the global asymptotic stability of the proposed
      methodology using positive-real lemma along with the LaSalle's invariance
      principle and experimentally validate using measured frequency response function.
      Moreover, the efficacy of the proposed technique compared to that of the linear
      controller is experimentally demonstrated on a benchmark rotary servo system.
      Experimental results assessed using the tracking error and cumulative power
      spectral density substantiate that the proposed control strategy can not only
      improve the low-frequency disturbance rejection but also augment the high
      frequency trajectory tracking performance.

PMID- 30093106
TI  - [Educational assessment of the first computerized national ranking exam in France
      in 2016: Opportunities for improvement].
AB  - In June 2016, 8124 medical students in their sixth year of graduation passed the
      first computerized national ranking exam (CNRE) in France after which they will
      have to choose what medical specialty they will be practicing all their life. We
      conducted the first educational assessment of this CNRE according to two
      criteria: the relevance of the questions and the cognitive domain mainly required
      to answer these questions. We propose two improvements for the future CNRE:
      promote student reasoning in the multiple choices questions, reduce to 10 the
      number of multiple choice questions in the progressive clinical cases and
      increase by 9 their total number (from 18 to 27), and use a majority of mini
      clinical cases for isolated multiple choice questions in order to focus students
      on reasoning instead of simple knowledge restitution.

PMID- 30093107
TI  - Biochemical analysis of human tRNAHis guanylyltransferase in mitochondrial
      tRNAHis maturation.
AB  - Mitochondria contain their own protein synthesis machinery, which includes
      mitochondrial tRNA maturation. It has been suggested that mammalian mitochondrial
      tRNAHis (mtRNAHis) is matured by post-transcriptional addition of guanosine at
      the -1 position (G-1), which serves as an identity element for mitochondrial
      histidyl-tRNA synthetase. However, the exact maturation process of mammalian
      mtRNAHis remains unclear. In cytoplasmic tRNAHis (ctRNAHis) maturation, tRNAHis
      guanylyltransferase (Thg1) adds a GTP onto the 5'-terminal of ctRNAHis and then
      removes the 5'-pyrophosphate to yield the mature 5'-monophospholylated G-1
      ctRNAHis (pG-1-ctRNAHis). Although mammalian Thg1 is localized to both the
      cytoplasm and mitochondria, it remains unclear whether mammalian Thg1 plays a
      role in mtRNAHis maturation in mitochondria. Here, we demonstrated that human
      Thg1 (hThg1) catalyzes the G-1 addition reaction for both human ctRNAHis and
      mtRNAHis through recognition of the anticodon. While hThg1 catalyzed consecutive
      GTP additions to mtRNAHisin vitro, it did not exhibit any activity toward mature
      pG-1-mtRNAHis. We further found that hThg1 could add a GMP directly to the 5'
      terminal of mtRNAHis in a template-dependent manner, but fungal Thg1 could not.
      Therefore, we hypothesized that acceleration of the pyrophosphate removal
      activity before or after the G-1 addition reaction is a key feature of hThg1 for
      maintaining a normal 5'-terminal of mtRNAHis in human mitochondria. This study
      provided a new insight into the differences between tRNAHis maturation in the
      cytoplasm and mitochondria of humans.

PMID- 30093109
TI  - Effects of low-magnitude high-frequency vibration on osteoblasts are dependent on
      estrogen receptor alpha signaling and cytoskeletal remodeling.
AB  - Clinical and experimental studies demonstrate the potential of low-magnitude high
      frequency vibration (LMHFV) to enhance bone formation in the intact skeleton and
      during fracture healing. Moreover, it was shown that the effects of vibration
      therapy during fracture healing are highly dependent on the estrogen status of
      the vibrated individual and that estrogen receptor (ER) alpha signaling plays a
      major role in mechanotransduction of LMHFV. Because it is known that LMHFV can
      directly act on osteogenic cells, we hypothesize that the differential effects of
      LMHFV in the presence and absence of estrogen are mediated by ERalpha signaling
      in osteoblasts. To prove this hypothesis, we subjected preosteoblastic MC3T3-E1
      cells and primary osteoblasts to LMHFV in vitro. We found increased Cox2 gene
      expression, cell metabolic activity and cell proliferation after LMHFV in the
      absence of estrogen, whereas the effects were contrary in the presence of
      estrogen. Blocking of ERalpha signaling by Esr1-siRNA knockdown or adding the
      selective ERalpha antagonist MPP dihydrochloride abolished the effects of LMHFV
      on osteoblast proliferation and Cox2 expression. Furthermore, primary osteoblasts
      isolated from ERalpha-knockout mice did not show a response towards LMHFV in the
      presence of estrogen. Additionally, blocking of actin cytoskeletal remodeling by
      adding the p160ROCK inhibitor Y-27632 abolished the effects of LMHFV. In
      contrast, expression of primary cilium was not necessary for mechanotransduction
      of LMHFV. These results suggest that direct effects of LMHFV on osteoblasts are
      dependent on ERalpha signaling and cytoskeletal remodeling.

PMID- 30093108
TI  - 4-Hydroxy-tetrahydrodipicolinate reductase from Neisseria gonorrhoeae - structure
      and interactions with coenzymes and substrate analog.
AB  - Neisseria gonorrhoeae, an obligate human pathogen, is a leading cause of
      communicable diseases globally. Due to rapid development of drug resistance, the
      rate of successfully curing gonococcal infections is rapidly decreasing. Hence,
      research is being directed toward finding alternative drugs or drug targets to
      help eradicate these infections. 4-Hydroxy-tetrahydrodipicolinate reductase
      (DapB), an important enzyme in the meso-diaminopimelate pathway, is a promising
      target for the development of new antibiotics. This manuscript describes the
      first structure of DapB from N. gonorrhoeae determined at 1.85 A. This enzyme
      uses NAD(P)H as cofactor. Details of the interactions of the enzyme with its
      cofactors and a substrate analog/inhibitor are discussed. A large scale
      bioinformatics analysis of DapBs' sequences is also described.

PMID- 30093110
TI  - LncRNA snaR upregulates GRB2-associated binding protein 2 and promotes
      proliferation of ovarian carcinoma cells.
AB  - BACKGROUND: The functionality of lncRNA snaR has only been characterized in
      breast cancer and colon cancer. The aim of the current study is to explore the
      involvement of lncRNA snaR in ovarian carcinoma (OC). MATERIALS AND METHODS:
      Expression of lncRNA snaR and GRB2-associated binding protein 2 (GAB2) in plasma
      of both patients with OC and healthy females was detected by qRT-PCR. Application
      value of plasma lncRNA snaR in the diagnosis of OC was evaluated by ROC analysis.
      Correlation between plasma lncRNA snaR and GAB2 was analyzed by Pearson
      correlation coefficient. LncRNA snaR and GAB2 expression vectors as well as GAB2
      siRNA were transfected into cells of human OC cell lines, and the effect on
      lncRNA snaR expression, GAB2 expression and cell proliferation was detected by
      qRT-PCR, western blot and CCK-8 assay. RESULTS: It was observed that plasma
      levels of lncRNA snaR and GAB2 were significantly higher in OC patients than
      those in healthy controls. In effect, high levels of plasma lncRNA snaR and GAB2
      distinguished OC patients from healthy controls. Plasma lncRNA snaR and GAB2 were
      positively correlated in OC patients but not in healthy controls. LncRNA snaR
      overexpression promoted cancer cell proliferation and upregulated GAB2
      expression. CONCLUSIONS: GAB2 overexpression also promoted cancer cell
      proliferation but showed no significant effects on lncRNA snaR expression, while
      GAB2 siRNA silencing significantly attenuated the enhancing effects of lncRNA
      snaR overexpression on cancer cell proliferation. LncRNA snaR may promote
      proliferation of ovarian carcinoma cells by upregulating GAB2 expression.

PMID- 30093111
TI  - Direct effects of Ca2+/calmodulin on actin filament formation.
AB  - Actin filament formation plays a pivotal role in the development, regeneration
      and modulation of the morphologies and physiological functions of subcellular
      compartments and entire cells. All of these processes require tight temporal and
      spatial control of F-actin assembly. Recent work has shed new light on the
      control of actin filament formation by Ca2+ as very fast, transient messenger
      allowing for defined responses to signal intensities spanning several orders of
      magnitude. Recent discoveries highlight that a small but rapidly growing set of
      actin nucleators and related proteins, i.e. factors that have the power to
      promote the formation of new actin filaments in cells, are tightly controlled by
      the Ca2+ sensor protein CaM. We here review the cellular functions and the
      molecular mechanisms that couple Ca2+ signaling to the cytoskeletal functions of
      these factors. This set of proteins currently includes one actin nucleator of the
      formin family (INF2), the WH2 domain-based actin nucleator Cobl and its ancestor
      protein Cobl-like as well as fesselin/synaptopodin-2/myopodin and myelin basic
      protein (MBP). Considering the mechanistic principles of Ca2+ control of actin
      filament formation unveiled thus far and the diverse cell biological processes
      involving Ca2+ signaling it is obvious that our understanding of the cell
      biological crosstalk of Ca2+ transients with the in part highly specialized actin
      cytoskeletal structures observed in different cell types is only at its infancy.

PMID- 30093112
TI  - The miR-15b-5p/PDK4 axis regulates osteosarcoma proliferation through modulation
      of the Warburg effect.
AB  - Blocking aerobic glycolysis has been proposed as an attractive therapeutic
      strategy for impairing the proliferation of cancer cells. However, the underlying
      mechanisms are poorly understood. Here, we show that miR-15b-5p was downregulated
      in osteosarcoma (OS) and that lower expression of miR-15b-5p promoted
      proliferation and contributed to the Warburg effect in OS cells. Mechanistically,
      miR-15b-5p acted as a tumor suppressor in OS by directly targeting pyruvate
      dehydrogenase kinase-4 and inhibiting its expression. These results reveal a
      previously unknown function of miR-15b-5p in OS, which is associated with
      metabolic alterations that promote cancer progression. miR-15b-5p may play an
      essential role in the molecular therapy of patients with OS.

PMID- 30093113
TI  - Rapid kinetics of changes in oxygen consumption rate in thrombin-stimulated
      platelets measured by high-resolution respirometry.
AB  - Platelet activation plays a key role in normal haemostasis and pathological
      thrombosis. Platelet activation is rapid; within minutes of stimulation,
      platelets generate bioactive phospholipids, secrete their granule contents,
      activate integrins and aggregate together to form a haemostatic plug. These
      events are dependent on ATP synthesis. Mitochondrial function in platelets from
      healthy volunteers and patients with a range of diseases indicate an important
      role for oxygen consumption in oxidative phosphorylation in normal and
      pathological function. Platelets also consume oxygen during oxidation reactions,
      such as cyclooxygenase-dependent thromboxane A2 synthesis. In this study, we used
      high-resolution respirometry to investigate rapid changes in oxygen consumption
      during platelet activation. We demonstrated a rapid, transient increase in oxygen
      consumption rate within minutes of platelet stimulation by the physiological
      activator, thrombin. This was partly inhibited by aspirin and by oligomycin. This
      shows that high resolution respirometry can provide information regarding rapid
      and dynamic changes in oxygen consumption during platelet activation.

PMID- 30093114
TI  - Anti-obesity potential of Glycyrrhiza uralensis and licochalcone A through
      induction of adipocyte browning.
AB  - The main function of brown adipose tissue is to dissipate surplus caloric intake
      into heat energy by thermogenesis, increasing energy expenditure. Inducible brown
      adipocytes can develop within white adipose tissue (WAT) through a process
      referred to as browning. Browning of white fat represents a promising strategy
      for treatment of obesity and the related complications. We investigated whether
      Glycyrrhiza uralensis and its ingredients modulated adipogenesis through
      adipocyte browning using 3T3-L1 adipocytes and a high-fat diet (HFD)-induced
      obesity mice model. Amongst extracts and fractions of G. uralensis, methyl
      dichloride (MeCl2) fraction was the most effective to induce expression of
      uncoupling protein 1 (UCP1), a fat browning marker, in 3T3-L1 adipocytes.
      Ingredients of G. uralensis such as licochalcone A (LicoA), isoliquiritigenin,
      and liquiritigenin induced UCP1 expression in 3T3-L1 adipocytes. After inducing
      obesity in mice by 6-week HFD, MeCl2 fraction of G. uralensis or LicoA was
      intraperitoneally administered for additional 19 days. MeCl2 fraction or LicoA
      significantly reduced body weight gain and inguinal fat pad weights. Furthermore,
      MeCl2 fraction or LicoA improved metabolic disorders induced by HFD as the
      treatments decreased serum levels of glucose and cholesterol, and blocked insulin
      resistance. MeCl2 fraction or LicoA enhanced expression of brown fat markers such
      as UCP1, PRDM16, and PGC-1alpha and increased brown fat phenotype population in
      inguinal WAT of HFD-fed mice. Our results demonstrate that G. uralensis and LicoA
      are effective to reduce obesity and to recover metabolic homeostasis by inducing
      the brown fat phenotype.

PMID- 30093115
TI  - Intraperitoneal injection of MSC-derived exosomes prevent experimental
      bronchopulmonary dysplasia.
AB  - Mesenchymal stromal cell (MSC) derived exosomes mediate tissue protection and
      regeneration in many injuries and diseases by modulating cell protein production,
      protecting from apoptosis, inhibiting inflammation, and increasing angiogenesis.
      In the present study, daily intraperitoneal injection of MSC-derived exosomes
      protected alveolarization and angiogenesis in a newborn rat model of
      bronchopulmonary dysplasia (BPD) induced by 14 days of neonatal hyperoxia
      exposure (85% O2). Exosome treatment during hyperoxia prevented disruption of
      alveolar growth, increased small blood vessel number, and inhibited right heart
      hypertrophy at P14, P21, and P56. In vitro, exosomes significantly increased tube
      like network formation by HUVEC, in part through a VEGF mediated mechanism. In
      summary, daily intraperitoneal injection of exosomes increased blood vessel
      number and size in the lung through pro-angiogenic mechanisms. MSC-derived
      exosomes therefore have both anti-inflammatory and pro-angiogenic mechanism to
      protect the lung from hyperoxia induced lung and heart disease associated with
      BPD.

PMID- 30093116
TI  - Lysophosphatidic acid receptor-2 (LPA2) and LPA5 regulate cellular functions
      during tumor progression in fibrosarcoma HT1080 cells.
AB  - Lysophosphatidic acid (LPA) receptors (LPA1 to LPA6) regulate a variety of
      malignant properties in cancer cells. In the present study, we investigated the
      roles of LPA receptors in the promotion of cellular functions during tumor
      progression in fibrosarcoma cells. To obtain long-term anticancer drug treated
      cells, human fibrosarcoma HT1080 cells were treated with methotrexate (MTX) and
      cisplatin (CDDP) for 6 months. LPAR2 and LPAR5 expressions were significantly
      higher in MTX-treated (HT-MTX) cells than in HT1080 cells. The cell motile and
      invasive activities of HT-MTX cells were significantly elevated compared with
      HT1080 cells. Although LPAR5 expression was increased in MTX and CDDP treated (HT
      M-C) cells, no change of LPAR2 expression was observed. The cell motile and
      invasive activities of HT-M-C cells were lower than those of HT1080 cells.
      Moreover, to evaluate whether LPA receptors promote cell invasive activity,
      highly invasion (HT1080-M6) cells were established from HT1080 cells. The cell
      invasive activity of HT1080-M6 cells was approximately 4.5 times higher than
      HT1080 cell invasion. LPAR2 expression was markedly elevated in HT1080-M6 cells
      compared with HT1080 cells. The high cell invasion activity of HT1080-M6 cells
      was significantly suppressed by an antagonist of LPA2, H2L5186303. These results
      suggest that LPA2 acts as a key regulator of malignant properties in HT1080
      cells.

PMID- 30093117
TI  - Variability of color matching with different digital photography techniques and a
      gray reference card.
AB  - STATEMENT OF PROBLEM: Color matching in restorative and prosthetic dentistry is
      important for the success of dental treatments, although communication with the
      dental laboratory remains subjective, and studies of the performance of objective
      communication methods are lacking. PURPOSE: The purpose of this study was to
      evaluate color differences (DeltaE) and compare color luminosity (L*) values
      among different types of digital photography equipment used to document tooth
      color, with and without a gray reference card, and to determine whether the gray
      card could be used to standardize color assessment in dental photography.
      MATERIAL AND METHODS: Sixty photographs were made (n=10) using different
      equipment: a D7000 digital camera (Nikon Corp) with an 85-mm lens and wireless
      close-up flash (DC+WCF); close-up flash surrounded by 80 grams per square meter
      (gsm; specification of paper thickness) white printing paper (DC+WPP); ring flash
      (DC+RF); close-up flash attached to a dual-point rigid flash bracket (DC+DPRF);
      cross-polarizing filter attached to a close-up flash (DC+CPF); and iPhone 7 (I7).
      For all photographs, a gray reference card with known color values was positioned
      at the patients' mandibular teeth, acting as a parameter for the analysis of
      white-balanced digital photographs. Each photograph underwent white balance with
      the reference card and software. DeltaE were obtained from each piece of
      equipment by comparing images with and without white balance (original photo)
      with software and the smallest DeltaE achieved was used as the gold standard for
      comparisons of luminosity. Values of luminosity were subsequently obtained for
      the different equipment with and without white balancing the photographs; these
      values were compared using a general estimating equation with Huber-White
      standard error (alpha=.05). RESULTS: The use of a cross-polarizing filter was
      used as the gold standard for luminosity evaluation, as the smallest DeltaE (3.4)
      among photographs were observed when those with and without white balance were
      compared. Luminosity results from the cross-polarizing filter method (DC+CPF)
      were not significantly different from those of the DC+DPRF (P=.73), DC+WPP
      (P=.106), and DC+WCF (P=.551) groups but were statistically different from DC+RF
      (P=.028) and I7 groups (P<.001). Use of a gray card was significant when a ring
      flash (P=.008) or the iPhone (P=.023) were used but not statistically significant
      for the other groups (P>.05). CONCLUSIONS: The use of a cross-polarizing filter
      results in more color-standardized photographs, while the ring flash system and
      the iPhone 7 result in less standardized photographs. The gray reference card had
      a significant effect when a ring flash system or iPhone 7 was used.

PMID- 30093118
TI  - Digital workflow to provide an immediate interim restoration after single-implant
      placement by using a surgical guide and a matrix-positioning device.
AB  - This article describes a workflow based on a top-down approach to provide a fixed
      type immediate interim restoration after placing a single implant using a
      digitally driven surgical guide and a matrix-positioning device. A characteristic
      of the technique is that both the surgical guide and the matrix-positioning
      device are fabricated from a single diagnostic virtual trial restoration designed
      on computer-aided design (CAD) software. This workflow may shorten the time
      required for chairside placement of an interim restoration and enhance esthetics
      when rehabilitating anterior teeth.

PMID- 30093120
TI  - Prosthetic rehabilitation of a maxillary defect with a bone anchored prosthesis:
      A clinical report.
AB  - Mucormycosis is an opportunistic fungal infection that frequently infects
      sinuses, brain, or lungs and arises mostly in immunocompromised patients.
      Although its occurrence in the maxilla is rare, debridement and resection of the
      infected and necrotic area is often the best treatment but usually results in an
      extensive maxillary defect. Protocols for prosthetic obturation versus
      microvascular reconstruction have been established and used effectively in
      tertiary institutions for patients with such large defects. Aramany Class VI
      defects involving more than half of the palatal surface can be managed
      effectively by surgical reconstruction using microvascular free flaps as a
      platform for supporting bone-anchored prostheses. Providing fixed prostheses may
      offer advantages over a conventional obturator prosthesis in terms of hygiene,
      function, and esthetics. Nonetheless, fixed prostheses retained by endosseous
      implants in patients with reconstructive osteomyocutaneous flaps often require a
      sequential team approach by the surgeon and prosthodontist. This clinical report
      describes the reconstruction of a maxilla by using a scapular free flap with
      subsequent prosthetic rehabilitation in a patient with maxillary sinus infection
      secondary to mucormycosis.

PMID- 30093119
TI  - Randomized controlled trial comparing immediate loading with conventional loading
      using cone-anchored implant-supported screw-retained removable prostheses: A 2
      year follow-up clinical trial.
AB  - STATEMENT OF PROBLEM: Implant-based prosthetic solutions can be time consuming.
      If implants can be loaded immediately, treatment time can be reduced. PURPOSE:
      The purpose of this prospective randomized controlled trial was to monitor the
      survival rate of Ankylos implants, comparing conventional with immediate loading
      by using abutments with the SynCone concept for screw-retained removable
      prostheses in the edentulous maxilla. MATERIAL AND METHODS: A total of 90
      implants were placed in 15 study participants. The participants were randomly
      assigned to the immediate or conventional loading treatment group. Radiographic
      and clinical parameters were recorded at the time of permanent prosthesis
      installment and at 1- and 2-year follow-up examinations, and participants'
      satisfaction was measured by using questionnaires before and after prosthesis
      installation. A linear mixed model was used to measure differences. RESULTS: One
      implant in the conventional group was lost during abutment placement; hence, 89
      implants could be followed for 2 years. Approximately 90% of these implants
      showed no bone loss or even bone gain at 1 and 2 years follow-up. Mean values for
      the immediate group were, respectively, 0.09 +/-0.35 mm and 0.13 +/-0.38 mm and
      0.01 +/-0.41 mm and -0.06 +/-0.32 mm for the conventional method. No significant
      differences (P=.053) were found in bone level alterations between the groups. For
      all participants, the mean number of surfaces (4 per implant) with bleeding on
      probing (BoP) and plaque were 0.76 +/-0.81 and 0.16 +/-0.42 at 1 year follow-up
      and 0.44 +/-0.66 and 0.02 +/-0.15, respectively, at the second-year follow-up.
      The mean pocket probing depths were 2.05 +/-0.54 mm at 1 year and 2.18 +/-0.64 mm
      at 2 years. For both groups, a significant rise in satisfaction and quality of
      life was observed (P<=.001) at 1 and 2 years compared with pretreatment.
      CONCLUSIONS: Ankylos implants placed in the edentulous maxilla, immediately or
      conventionally loaded by a detachable prosthesis, showed favorable bone-level
      preservation after 2 years of follow-up. No significant differences could be
      found between the immediate and conventional groups. A significant increase in
      quality of life was observed for both loading modes.

PMID- 30093121
TI  - Digital tools and 3D printing technologies integrated into the workflow of
      restorative treatment: A clinical report.
AB  - The development of technologies including intraoral scanners, dental software for
      digital restoration design, and additive manufacturing has improved the digital
      workflow of restorative treatment. The present article describes a digital
      workflow with intraoral scanning, computer-aided design (CAD) software, and
      subtractive and additive manufacturing procedures for a patient receiving lithium
      disilicate laminate veneers.

PMID- 30093122
TI  - Mechanical integrity of cement- and screw-retained zirconium-lithium silicate
      glass-ceramic crowns to Morse taper implants.
AB  - STATEMENT OF PROBLEM: The improved esthetics of ceramic dental prostheses has
      increased their popularity, although their high elastic modulus and low fracture
      toughness and tensile strength may reduce the long-term performance of dental
      prostheses. PURPOSE: The purpose of this in vitro study was to assess the
      mechanical integrity of zirconium-lithium silicate glass-ceramic crowns cement-
      and screw-retained to a titanium implant-abutment after fatigue. MATERIAL AND
      METHODS: Forty titanium implants were placed in polyacetal to mimic bone support.
      Abutments were tightened to the implants to 20 Ncm by using a digital handheld
      torque meter. The implant abutment assemblies received a pressed maxillary
      premolar crown, either lithium disilicate (LD) or zirconium-lithium silicate
      glass-ceramic (LZS). The specimens (n=10) were subjected to fatigue at 200 N and
      5 Hz for 500 000 cycles in a Ringer electrolytic solution (37 degrees C). After
      fatigue, the crowns were removed to evaluate removal torque values on the implant
      abutment connection. The remaining crown-implant-abutment assemblies were cross
      sectioned at 90 degrees to the implant-abutment joint for inspection of cracks
      and the micro-gaps by scanning electron microscopy. RESULTS: Removal torque
      values before fatigue were recorded at 18 +/-1.63 Ncm for the LD group and 18.2
      +/-0.81 Ncm for the LZS group. After fatigue, the removal torque values decreased
      significantly (12.8 +/-1.6 Ncm for LD, 14.9 +/-1.08 Ncm for LZS; P<.05). Micro
      gaps at the implant-abutment connections were measured at 0.9 +/-0.3 MUm before
      fatigue and at 4.2 +/-0.9 MUm after fatigue. Cracks were detected at the crown
      adhesive or at the adhesive-abutment interface for both systems after fatigue.
      CONCLUSIONS: Cement- and screw-retained implant zirconium-lithium silicate glass
      ceramic crowns revealed effective fatigue resistance on mean cyclic loading in an
      electrolyte solution. However, mechanical instability of the crown-adhesive
      abutment interfaces and implant-abutment joints was detected after fatigue.

PMID- 30093123
TI  - Obtaining reliable intraoral digital scans for an implant-supported complete-arch
      prosthesis: A dental technique.
AB  - This article describes a technique for obtaining an accurate complete-arch
      digital scan for an edentulous patient. To achieve this, an auxiliary polymeric
      device that simulates a denture is designed, fabricated, and placed in the mouth.
      This device, having the geometry of a typical dental arch, facilitates the
      digitalization of the edentulous complete arch. This is because the change in
      radius of the curvature (change of geometry) enables the scanner to perform a
      more accurate alignment. Initially, the necessary location of the implants is
      acquired, and then the soft tissue is added. This technique can achieve accurate
      complete-arch digital scans. Distances between implants are closer to the gold
      standard when using this auxiliary geometry piece than those obtained without
      using it.

PMID- 30093124
TI  - Erratum.

PMID- 30093125
TI  - Management of denture-related traumatic ulcers using ozone.
AB  - STATEMENT OF PROBLEM: Management of denture-related traumatic ulcers using ozone
      may improve tissue healing and reduce patient pain and discomfort. PURPOSE: The
      purpose of this clinical investigation was to assess the efficacy of ozone in the
      treatment of denture-related traumatic ulcers. MATERIAL AND METHODS: Seventy-five
      participants (study group) with denture-related traumatic ulcers were evaluated
      in this blinded, controlled cohort observational investigation. A control group
      (n=75) of participants with denture-related traumatic ulcers who matched the
      study group in sex and age were also recruited. Ulcers were treated with ozone
      gas for 60 seconds in the study group and with air for 60 seconds in the control
      group. Pain levels were evaluated by means of a visual analog scale (VAS), and
      ulcer sizes were measured in each participant at experiment baseline and each day
      for 15 days. Ulcer duration was established by calculating the period it took to
      completely heal and disappear. Major outcome measurements were ulcer duration,
      ulcer size, and levels of pain. RESULTS: Ulcer size decreased from day 2 in the
      study group (after ozone application) (P<=.01) and from day 4 in the controls
      (P<=.001). Recorded pain levels decreased from the first day soon after ozone
      application in the study group (P<=.001) and from day 3 in the controls (P<.001).
      Ulcer duration, ulcer size from day 3 to day 10, and reported pain levels from
      day 1 to day 10 decreased more in the study group (P<=.004). CONCLUSIONS:
      Exposure of denture-related traumatic ulcers to 60 seconds of ozone gas was
      associated with better ulcer healing and decreased pain levels, ulcer size, and
      ulcer duration.

PMID- 30093126
TI  - Survival rate and load to failure of premolars restored with inlays: An
      evaluation of different inlay fabrication methods.
AB  - STATEMENT OF PROBLEM: Studies that evaluate the survival rate and load to
      fracture of premolars restored with inlays produced using different methods are
      lacking. PURPOSE: The purpose of this in vitro study was to compare the survival
      rate and fracture load of premolars restored with inlays fabricated using
      different methods. MATERIAL AND METHODS: Thirty maxillary premolars were
      selected, embedded, and prepared to receive inlays fabricated using different
      methods (n=10): LaCom-digital impression with Lava C.O.S. scanner (3M ESPE),
      followed by milling of composite resin block (Lava Ultimate; 3M ESPE) in a
      milling unit; CeCom-digital impression with Cerec 3D Bluecam scanner (Dentsply
      Sirona), followed by milling of a Lava Ultimate block in Cerec (Dentsply Sirona);
      PresDis-impression with polyvinyl siloxane, inlay made using the lost wax
      technique, and IPS e.max Press (Ivoclar Vivadent AG) pressed ceramic (lithium
      disilicate). A dual-polymerizing resin cement system was used to lute the inlays.
      Inlays were mechanically cycled (2 Hz, 106 mechanical pulses, 80 N) after 24
      hours, and the specimens were stored in distilled water at 37 degrees C for 11
      months. Then, a fatigue test was conducted using a 10-Hz frequency and 400-N load
      on the inner inclines of the cusps. The test was complete when the specimen
      fractured or when the specimen reached 1.5*106 cycles. The specimens that
      survived fatigue testing were submitted to a single-load fracture test in a
      universal testing machine and analyzed using a stereoscope for failure
      classification. Survival rates were estimated using the Kaplan-Meier method and
      log-rank test (Mantel-Cox). Fracture load data were analyzed using 1-way ANOVA
      (alpha=.05). RESULTS: No significant differences were detected among the groups
      for the survival rate (P=.87) or for the load to fracture (P=.78). Most failures
      were longitudinal, catastrophic fractures. CONCLUSIONS: Premolars restored with
      inlays fabricated using the tested methods had similar survival rates and loads
      to fracture.

PMID- 30093127
TI  - Changes in hardness of addition-polymerizing silicone-resilient denture liners
      after storage in artificial saliva.
AB  - STATEMENT OF PROBLEM: The hardness of silicone resilient denture liners was
      reported to be more stable than that of acrylic resin resilient denture liners.
      However, the changes in hardness of these materials in artificial saliva are
      unclear. PURPOSE: The purpose of this in vitro study was to evaluate changes in
      the hardness of addition-polymerizing silicone-resilient denture liners for long
      term use after storage in artificial saliva. MATERIAL AND METHODS: Four addition
      polymerizing silicone resilient denture liners were tested: GC Reline Soft, Elite
      Soft Relining, Megabase, and Mucopren Soft. All were long-term relining materials
      of the soft type. Fifteen disk-shaped specimens were prepared for each of the
      tested materials (40 mm in base diameter, 8 mm in thickness). Their initial
      hardness was assessed with a Shore A durometer, after which they were stored in
      artificial saliva at a temperature of 37 degrees C. Hardness was examined after
      7, 30, and 90 days. Statistical analysis was performed using parametric ANOVA for
      dependent and independent variables and Tukey honest significant difference (HSD)
      post hoc tests (alpha=.05). RESULTS: All resilient denture liners increased in
      hardness during the experiment. The change was least for Elite Soft Relining, and
      GC Reline Soft was the hardest material. Initially, Megabase and Mucopren Soft
      were significantly softer than the other 2 materials, but their hardness
      increased rapidly after the first 7 days of specimen conditioning, achieving
      values close to Elite Soft Relining. CONCLUSIONS: Within the limitations of the
      study, room temperature vulcanizing addition-polymerizing polyvinyl siloxanes of
      the soft type have different initial hardness, and this changes with storage time
      in artificial saliva at the temperature of the oral cavity.

PMID- 30093128
TI  - Management of an edentulous patient with temporomandibular disorders by using CAD
      CAM prostheses: A clinical report.
AB  - This clinical report describes the application of computer-aided design and
      computer-aided manufacturing (CAD-CAM) complete dentures (CDs) in 4 visits and a
      2-year follow-up period for a patient with temporomandibular disorders (TMDs),
      severe occlusal disturbances, and parafunctional habits. The use of a Gothic arch
      tracing for recording the maxillomandibular relationship and verifying muscular
      function was particularly helpful in such a symptomatic patient. A trial period
      was used to determine patient acceptance and adaptation to the new CDs.

PMID- 30093129
TI  - Accurate repositioning of an implant interim restoration into the definitive
      impression to obtain an exact reproduction of tissue contours in the soft tissue
      cast.

PMID- 30093130
TI  - Changes in the esthetic, physical, and biological properties of a titanium alloy
      abutment treated by anodic oxidation.
AB  - STATEMENT OF PROBLEM: The grayish appearance of titanium abutments adversely
      affects peri-implant esthetics in patients with thin mucosa, impacting patient
      satisfaction with implant-supported restorations in esthetic regions. PURPOSE:
      The purpose of this in vitro study was to change the color of titanium alloys
      with anodic oxidation and to evaluate alterations in the esthetic, physical, and
      biological properties of the anodized titanium alloys. MATERIAL AND METHODS: Pink
      and yellow titanium alloys produced by anodization were the experimental groups,
      and the untreated titanium alloy and zirconia were used as the control groups.
      Pig gingiva was placed on the tested specimens to evaluate the esthetic effect by
      recording the color change in the gingiva. Physical properties including
      morphology, chemical composition, roughness, and contact angle were evaluated by
      scanning electron microscopy, atomic force microscopy, and a contact angle
      analysis system. Biological properties were evaluated by observing the cell
      behaviors of human gingival fibroblasts, using scanning electron microscopy,
      fluorescence microscopy, a live/dead viability assay, and a cell counting assay.
      RESULTS: A variety of colors can be produced on the surfaces of titanium alloys
      by anodization at different voltages. Titanium alloys anodized at 60 and 65 V
      exhibited yellow and pink appearances, respectively. Color differences of gingiva
      caused by anodized titanium alloys were lower than those of the untreated
      titanium alloy, but they were higher than those of zirconia. Compared with the
      untreated titanium alloy, the anodized titanium alloys exhibited grain formation,
      a lower contact angle, and higher roughness. Cell morphology, proliferation, and
      viability on surfaces of anodized titanium alloys were similar to those of the
      untreated titanium alloy but lower than those of zirconia. CONCLUSIONS:
      Anodization could change the color of titanium alloys to pink or yellow at
      different voltages. Grain formation, roughness, and hydrophilicity were increased
      after treatment. The esthetics and biocompatibility of anodized titanium alloys
      were not as good as that of zirconia, but the pink and yellow titanium alloys
      treated by anodization achieved better gingival esthetics than the untreated
      titanium alloy.

PMID- 30093132
TI  - Live Attenuated Influenza Vaccine: Is Past Performance a Guarantee of Future
      Results?
AB  - Live attenuated influenza vaccine (LAIV) has had a tumultuous recent history that
      can be difficult for many to follow and understand. Prior to 2013, LAIV had a
      record of accomplishment of providing equal or superior protection against
      influenza in children. Since 2013, concerns about the lack of protection with
      LAIV against pandemic H1N1 strains led to the withdrawal of any recommendation
      for use in the US by the Advisory Committee on Immunization Practices (ACIP).
      After some significant changes to the content, evaluation and production of LAIV,
      it has been be recommended again for use in the US in 2018-19. This commentary
      reviews the origin of LAIV, the events and circumstances that led to the
      withdrawal of any recommendation for LAIV use by the ACIP, the merits,
      shortcomings and repercussions of that decision and finally offers some thoughts
      about the future of LAIV.

PMID- 30093131
TI  - Effects of Dulaglutide and Insulin Glargine on Estimated Glomerular Filtration
      Rate in a Real-world Setting.
AB  - PURPOSE: The aims of this study were to use real-world treatment results to
      compare changes in estimated glomerular filtration rate (eGFR) and glycosylated
      hemoglobin (HbA1c) among patients with type 2 diabetes who initiated treatment
      with dulaglutide or insulin glargine and to determine the proportions of patients
      with renal impairment who initiate each treatment. METHODS: The study used data
      from the Practice Fusion electronic health records database from October 2013
      through June 2017. Adults with type 2 diabetes who initiated dulaglutide or
      insulin glargine therapy and had multiple recorded serum creatinine and/or HbA1c
      laboratory test results were included in the study. The dulaglutide cohort (n =
      1222) was matched to the insulin glargine cohort (n = 13,869) using Mahalanobis
      distance matching with propensity score calipers. Multivariable analyses of the
      matched cohorts of individuals with serum creatinine results (n = 1183
      dulaglutide and 1183 insulin glargine) examined the association between intent-to
      treat therapy and changes in eGFR. In addition, multivariable analyses were also
      conducted on a subset of these patients who also had recorded HbA1c tests (n =
      1088 dulaglutide and 1088 insulin glargine) to examine the association between
      changes in HbA1c during the 1 year postperiod. FINDINGS: Among patients who
      initiated dulaglutide therapy, only 0.9% of patients had an index eGFR <30 and
      >=15 mL/min/1.73 m2 and 0.1% had an index eGFR <15 mL/min/1.73 m2. In contrast,
      4.1% of insulin glargine-treated patients had an index eGFR <30 and >=15
      mL/min/1.73 m2 and 1.2% had an index eGFR <15 mL/min/1.73 m2. Compared with
      patients who initiated therapy with insulin glargine, initiation of dulaglutide
      therapy was associated with a significantly smaller decrease in eGFR (-0.4 vs 
      0.9 mL/min/1.73 m2; P = 0.0024), a significantly smaller likelihood of having a
      30% or greater reduction in eGFR (3.3% vs 4.1%; P < 0.0001), and a significantly
      larger reduction in HbA1c (-0.5% vs -0.2%; P < 0.0001). IMPLICATIONS: In clinical
      practice, the use of dulaglutide was relatively more limited in patients with a
      higher degree of renal impairment compared with use of insulin glargine. However,
      initiation of dulaglutide therapy, compared with insulin glargine therapy, was
      associated with a significantly smaller decrease in eGFR and a larger reduction
      in HbA1c during the 1 year postperiod.

PMID- 30093134
TI  - Hot Topics in Viral Infections.

PMID- 30093133
TI  - Population Pharmacokinetic Analysis of Meropenem After Intravenous Infusion in
      Korean Patients With Acute Infections.
AB  - PURPOSE: The aim of this study was to investigate the population pharmacokinetic
      (PK) profile of meropenem in Korean patients with acute infections. METHODS: The
      study included 37 patients with a creatinine clearance <=50 or >50 mL/min who
      received a 500- or 1000-mg dose of meropenem, respectively, infused intravenously
      over 1 hour every 8 hours. Blood samples were collected before and at 1, 1.5, and
      5 hours after the start of the fourth infusion. The population PK analysis was
      conducted by using nonlinear mixed effect modeling software (NONMEM). Monte-Carlo
      simulations were performed to identify optimal dosing regimens. FINDINGS: Thirty
      seven subjects completed the study. Meropenem PK variables were well described by
      using a one-compartment model. The typical values (relative SE) for weight
      normalized clearance (CL) and Vd were 0.266 L/h/kg (12.29%) and 0.489 L/kg
      (11.01%), respectively. Meropenem CL was significantly influenced by the serum
      creatinine level, which explained 11% of the interindividual CK variability. The
      proposed equation to estimate meropenem CL in Korean patients was as follows: CL
      (L/h) = 0.266 * weight * [serum creatinine/0.74]-1.017. The simulation results
      indicate that the current meropenem dosing regimen may be suboptimal in patients
      infected with normal or augmented renal function. IMPLICATIONS: Prolonged
      infusions of meropenem over at least 2 hours should be considered, especially in
      patients with augmented renal function and those infected with pathogens for
      which the minimum inhibitory meropenem concentration is >1 MUg/mL. Our results
      suggest an individualized meropenem dosing regimen for patients with abnormal
      renal function and those infected with pathogens with decreased in vitro
      susceptibility.

PMID- 30093135
TI  - Pragmatic dissemination and implementation research models, methods and measures
      and their relevance for nursing research.
AB  - BACKGROUND: Pragmatic dissemination and implementation (D&I) research approaches
      can benefit patient care because they emphasize real-world settings and
      populations. Nurse scientists have an opportunity to reduce the gap between
      science and practice by using pragmatic D&I research and sustainability
      strategies. PURPOSE: This article discusses pragmatic models, methods, and
      measures used in D&I research and their relevance for nursing research and
      enhancing population health. METHODS: Summary of pragmatic D&I models and related
      methods for designing a pragmatic studies. We discuss the RE-AIM framework and
      the PRECIS-2 planning aid and figure in detail. A case study is provided and
      application to nursing research is discussed. DISCUSSION: Successful translation
      of pragmatic D&I research demands an approach that addresses external validity,
      and customization at multiple levels including the patient, clinician, and
      setting. Context is critically important, and it is never too early to design for
      dissemination. CONCLUSIONS: Pragmatic D&I approaches are needed to speed research
      translation, reduce avoidable waste of funding, improve clinical care, and
      enhance population health. Pragmatic D&I research is an area of tremendous
      opportunity for the nursing science community.

PMID- 30093136
TI  - Considerations in initiating genomic screening programs in health care systems.

PMID- 30093137
TI  - Effect of sacubitril/valsartan on cardiac filling pressures in patients with left
      ventricular systolic dysfunction.
AB  - BACKGROUND: Sacubitril/valsartan is the newest neurohormonal agent approved for
      therapy in patients with heart failure with reduced ejection fraction (HFrEF).
      Little is known about its acute and incremental hemodynamic effects. We aimed to
      evaluate the change in hemodynamic profiles measured using an implanted
      monitoring device in HFrEF patients initiated on sacubitril/valsartan therapy.
      METHODS: We prospectively enrolled 13 subjects with HFrEF and pre-implanted
      CardioMEMSTM device on maximally tolerated guideline-directed medical therapy and
      no contraindications to sacubitril/valsartan therapy. Transmitted pulmonary
      artery diastolic pressures (PAdP) from CardioMEMSTM were averaged and compared
      for one week before and after initiation of sacubitril/valsartan, as well as
      after change in medication strength and finally at three months. RESULTS:
      Sacubitril/valsartan dose increase was tolerated in 7/13 subjects with drug
      discontinuation in one subject after a week due to renal dysfunction. There was a
      significant reduction in mean PAdP after sacubitril/valsartan initiation compared
      to standard therapy (20.8 vs 18.3 mm Hg, p = 0.020). No further PAdP reduction
      was noted after sacubitril/valsartan dose increase (19.7 vs 20 mm Hg, p = 0.673)
      and at 3-month follow-up compared to baseline (20.8 vs 19.2 mm Hg, p = 0.352).
      CONCLUSIONS: Sacubitril/valsartan causes an acute reduction mean pulmonary artery
      pressures after initiation. However, no incremental reduction in PAdP was noted
      after dose increase and short-term follow-up. The current study demonstrates the
      utility of CardioMemsTM device to study the drug's impact on hemodynamic profile
      in both short- and long-term follow-up.

PMID- 30093139
TI  - Does second-generation cryoballoon ablation using the current single short freeze
      strategy produce pulmonary vein stenosis?
AB  - BACKGROUND: Few data are available regarding pulmonary vein (PV) stenosis after
      second-generation cryoballoon PV isolation (CB2-PVI). Currently, a single short
      freeze strategy is standard for CB2-PVI owing to enhanced cooling effects. This
      study aimed to evaluate the incidence of PV stenosis after CB2-PVI with the
      current standard strategy. METHODS: Two hundred seventy-six atrial fibrillation
      patients underwent CB2-PVI using one 28-mm balloon and single 3-minute freeze
      strategy. If balloon temperatures reached -60  degrees C or phrenic nerve injury
      was suspected, freezing was terminated. Enhanced cardiac computed tomography (CT)
      was obtained before and >3 months after the procedure. RESULTS: Overall, 1067 of
      1101 (96.9%) PVs were isolated with cryoballoons, while the remaining 34 PVs
      required touch-up ablation. The total application number/patient was 5.1 +/- 1.4,
      and total application time 216 +/- 104, 205 +/- 77, 186 +/- 68, and 246 +/- 142 s
      for the left superior (LSPV), left inferior (LIPV), right superior (RSPV), and
      right inferior PVs, respectively. Follow-up CT obtained a median of 5.0 [3.3-7.0]
      months post-procedure revealed no PVs with moderate or severe stenosis.
      Asymptomatic mild stenosis was documented in 16 total (1.4%) PVs (5 LSPVs, 5
      LIPVs, and 6 RSPVs), but not in right inferior, left common, right middle, or PVs
      requiring touch-up ablation. Mild stenosis did not progress during the follow-up.
      Among the potential factors associated with PV stenosis, longer application times
      were the sole significant factor associated with mild RSPV stenosis. CONCLUSIONS:
      In CB2-PVI with the current single short freeze strategy, the risk of PV stenosis
      is extremely low, and routine follow-up imaging for evaluation seems not to be
      necessary.

PMID- 30093140
TI  - Medication-related osteonecrosis of the jaw - Personal comments.

PMID- 30093138
TI  - Comparison of long-term clinical outcomes between revascularization versus
      medical treatment in patients with silent myocardial ischemia.
AB  - BACKGROUND: There have been limited and conflicting results regarding the
      prognostic impact of revascularization treatment on the long-term clinical
      outcomes of silent ischemia. The current study aimed to determine whether
      revascularization treatment compared with medical treatment (MT) alone reduces
      long-term risk of cardiac death of asymptomatic patients with objective evidence
      of inducible myocardial ischemia. METHODS: A total of 1473 consecutive
      asymptomatic patients with evidence of inducible myocardial ischemia were
      selected from a prospective institutional registry. All patients showed at least
      1 epicardial coronary stenosis with >=50% diameter stenosis in coronary
      angiography. Patients were classified according to their treatment strategies.
      The primary outcome was cardiac death up to 10 years. RESULTS: Among the total
      population, 709 patients (48.1%) received revascularization treatment including
      percutaneous coronary intervention (PCI, n = 558) or coronary artery bypass graft
      surgery (CABG, n = 151), with the remaining patients (764 patients, 51.9%)
      receiving MT alone. During the follow-up period, the revascularization treatment
      group showed a significantly lower risk of cardiac death compared with the MT
      alone group (25.4% vs. 33.7%, HR 0.624, 95%CI 0.498-0.781, p < 0.001). Among
      revascularized patients, patients with negative non-invasive stress test results
      after revascularization showed significantly lower risk of cardiac death compared
      to those with residual myocardial ischemia (8.9% vs. 18.7%, HR 0.406, 95% CI
      0.175-0.942, p = 0.036). CONCLUSIONS: In patients with silent myocardial
      ischemia, revascularization treatment was associated with significantly lower
      long-term risk of cardiac death compared with the MT alone group. The current
      results support contemporary practice of ischemia-directed revascularization,
      even in patients with silent myocardial ischemia.

PMID- 30093141
TI  - Mutation screening of NEK1 in Chinese ALS patients.
AB  - NEK1 was recently identified as an amyotrophic lateral sclerosis (ALS) gene
      through rare variant burden analysis, and its role in ALS in various populations
      is still unclear. The aim of this study was to determine the frequency and
      spectrum of NEK1 mutations in an ALS cohort from mainland China. All exons and
      their flanking intron regions of NEK1 were screened by direct nucleotide
      sequencing in 377 unrelated ALS patients. These patients were also screened with
      a massive parallel sequencing gene panel for 24 known ALS genes and C9orf72
      hexanucleotide repeat expansion. In totality, we detected 9 variants, comprising
      3 novel heterozygous loss-of-function mutations and 6 rare missense variants (MAF
      < 0.1%) in NEK1. The patient with splice site mutation also carried another
      probably damaging variant in SOD1. Our study established a NEK1 mutant frequency
      of 0.8% in Chinese ALS patients, further expanded its spectrum of variants, and
      highlighted the possibility of coexistence with variants in additional ALS genes
      in NEK1 loss-of-function carriers.

PMID- 30093142
TI  - Audacious Psyche: Visualizing Evolution in John Pringle Nichol's Romantic
      Universe.
AB  - John Pringle Nichol (1804-1859), a Scottish Romantic astronomer, educator, and
      social reformer, used visual representations to develop and communicate key
      elements of his theory of evolution as a universal principle. Examining four of
      the diverse representations that appeared in Nichol's popular science books
      between 1846 and 1850 reveals the rich possibilities of evolutionary imagery
      prior to the emergence of more dominant forms of representation in the wake of
      Charles Darwin's On the Origin of Species (1859). The abstract and schematic
      nature of many of Nichol's visual representations-which included line diagrams
      and imaginative, mythic imagery (the latter developed in collaboration with the
      Scottish Romantic artist David Scott)-made them apt vessels for his Romantic
      evolutionary concepts, because a single image could simultaneously represent
      features of evolution across multiple domains, reflecting the Romantic concept of
      the unity of nature and the myriad analogies between its constituent parts. All
      of the images embodied narrative in one form or another and required use of the
      imagination in the act of interpretation. Many of the images facilitated the
      viewer's ability to conceptualize unobservable or only partially observable
      features of evolutionary change. Even as these visual representations acted as
      tools of perspective, insight, and clarity, they also helped to generate new
      ambiguities, such as a fundamental tension between teleology and contingency.

PMID- 30093143
TI  - Comparison of long-term clinical outcomes of external and internal pancreatic
      stents in pancreaticoduodenectomy: randomized controlled study.
AB  - BACKGROUND: To determine the most appropriate pancreatic drainage method, by
      investigating differences in 12-month clinical outcomes in patients implanted
      with external and internal pancreatic stents as an extension to a previous study
      on short-term outcome. METHODS: This prospective randomized controlled trial
      enrolled 213 patients who underwent pancreaticoduodenectomy with duct to mucosa
      pancreaticojejunostomy between August 2010 and January 2014 (NCT01023594). Of the
      185 patients followed-up for 12 months, 97 underwent external and 88 underwent
      internal stenting. Their long-term clinical outcomes were compared. RESULTS:
      Overall late complication rates were similar in the external and internal stent
      groups (P = 0.621). The percentage of patients with >50% atrophy of the remnant
      pancreatic volume after 12 months was similar in both groups (P = 0.580). Factors
      associated with pancreatic exocrine or endocrine function, including stool
      elastase level (P = 0.571) and rate of new-onset diabetes (P = 0.179), were also
      comparable. There were no significant between-group differences in quality of
      life, as evaluated by the EORTC QLQ-C30 and QLQ PAN26 questionnaires. CONCLUSION:
      External and internal stents showed comparable long-term, as well as short-term
      clinical outcomes, including late complication rates, preservation of pancreatic
      duct diameters, pancreatic volume changes with functional derangements, and
      quality of life after surgery.

PMID- 30093144
TI  - Pancreatectomy with arterial resection is superior to palliation in patients with
      borderline resectable or locally advanced pancreatic cancer.
AB  - BACKGROUND: Few studies have investigated the outcome of pancreatectomy
      associated with artery resection (PAR). METHODS: Retrospective analysis of a
      cohort of operated borderline or locally advanced pancreatic cancer patients with
      surgically confirmed arterial involvement. Short and long-term outcome were
      analyzed and compared in patients who underwent PAR (Group 1) and palliative
      surgery (Group 2). RESULTS: Of 73 patients who underwent surgical exploration
      with intent of resection, 34 underwent PAR (+/-venous resection) (Group 1) and 39
      underwent palliation (Group 2). 23 patients (67.7%) in Group 1 underwent combined
      artery-vein resection (AVR). Operation time was longer and blood loss higher in
      group 1 compared to group 2. There were no differences in post-operative
      mortality (2.9% vs 2.6%, p = 0.9) and post-operative surgical complications
      (38.2% vs 25.6%, p = 0.2). The 1, 3 and 5 years survival in Group 1 was superior
      to Group 2 (63.7%, 23.4% and Q3 23.4% vs 41.7%, 3.2% and 0, p = 0.003).
      CONCLUSION: PAR seems to be safe and feasible in well selected patients and
      associated with an advantage of survival compared to palliation, in patients
      affected by locally advanced pancreatic cancer.

PMID- 30093145
TI  - Interaction with Volume-Rendered Three-Dimensional Echocardiographic Images in
      Virtual Reality.

PMID- 30093146
TI  - Right Atrial Function Predicts Clinical Outcome in Patients with Precapillary
      Pulmonary Hypertension.
AB  - BACKGROUND: Although the primary role of right atrial (RA) size in the diagnosis
      and risk stratification of precapillary pulmonary hypertension (PH) has been
      studied, little is known about the clinical significance of RA function. In line
      with studies assessing left atrial function in heart failure, the aim of this
      study was to introduce the RA function index (RAFi) and to explore its prognostic
      power in precapillary PH. METHODS: RA emptying fraction was calculated as (RA end
      systolic volume - RA end-diastolic volume) * 100/(RA end-systolic volume). RAFi
      was calculated as (RA emptying fraction * right ventricular outflow tract
      velocity-time integral)/(RA end-systolic volume index). Patients were followed
      for the end point of clinical failure, which was defined as death,
      hospitalization because of PH, or disease progression. RESULTS: In total, 47
      patients with precapillary PH were included. Mean RAFi was 16.1 +/- 22.3%. Over a
      median follow-up period of 25 months (interquartile range, 9.5-41.1 months), 29
      patients experienced clinical failure. Univariate Cox proportional-hazard
      analysis showed that RAFi was a predictor of clinical failure (hazard ratio,
      0.935; 95% CI, 0.890-0.981; P = .007). Addition of RAFi to established predictors
      of outcomes, including 6-minute walk distance, N-terminal pro-B-type natriuretic
      peptide, and RA area, improved their prognostic power. CONCLUSIONS: RAFi is an
      easily assessed echocardiographic parameter, which is strongly predictive of
      clinical outcomes in patients with precapillary PH. Further studies are needed to
      validate RAFi and define its role in clinical practice.

PMID- 30093147
TI  - Temporal changes of major protein concentrations in preterm and term human milk.
      A prospective cohort study.
AB  - BACKGROUND: Proteins are major contributors to the beneficial effects of human
      milk (HM) on preterm infant health and development. Alpha-lactalbumin,
      lactoferrin, serum albumin and caseins represent approximately 85% of the total
      HM protein. The temporal changes of these proteins in preterm (PT) HM and its
      comparison with term (T) HM is poorly characterized. AIMS: To quantify and
      compare the temporal changes of the major proteins in PT HM and T HM. METHODS: HM
      was collected for 4 months postpartum at 12 time points for PT HM (gestational
      age 28 0/7-32 6/7 weeks; 280 samples) and for 2 months postpartum at 8 time
      points for T HM (gestational age 37 0/7-41 6/7 weeks; 220 samples). Proteins were
      measured with a micro-fluidic LabChip system. RESULTS: Casein, alpha-lactalbumin
      and lactoferrin decreased with advancing stages of lactation in PT and T HM,
      whereas serum albumin remained stable. Only marginal differences between PT and T
      HM were observed for alpha-lactalbumin during postpartum weeks 3-5 and for serum
      albumin at the first week. However, a comparison of HM provided to preterm and
      term infants at the same postmenstrual ages revealed that alpha-lactalbumin
      contents were significantly lower in PT HM than in T HM during the 39-48
      postmenstrual weeks. CONCLUSIONS: This study provides comprehensive information
      of the longitudinal changes of major proteins in PT and T HM, and suggests
      limited availability of alpha-lactalbumin, a nutritionally important protein, in
      breastfed PT infants after reaching the term corrected age. This information may
      be important to optimize HM protein fortification, although its biological
      relevance needs to be confirmed by intervention studies. CLINICAL TRIAL REGISTRY:
      ClinicalTrials.gov (NCT02052245),
      https://clinicaltrials.gov/ct2/show/NCT02052245.

PMID- 30093148
TI  - Bicuspid aortic valve aortopathy: One size fits all?

PMID- 30093149
TI  - Mentoring the newly minted: Evolving the rules of engagement.

PMID- 30093150
TI  - Plug before pave in chronic aortic dissections?

PMID- 30093151
TI  - Cardiac reoperation: Should that be a marker of quality?

PMID- 30093152
TI  - Four-dimensional flow magnetic resonance imaging: Beyond beautiful pictures!

PMID- 30093153
TI  - What to do when the acute type A aortic dissection involves the aortic sinuses.

PMID- 30093154
TI  - Perioperative renal function and thoracoabdominal aneurysm repair: Where do we go
      from here?

PMID- 30093155
TI  - Application of a neuroscience research model to study neuroprotection in children
      with congenital heart disease.

PMID- 30093158
TI  - Evolution of survivorship in lymphoma, myeloma and leukemia: Metamorphosis of the
      field into long term follow-up care.
AB  - Recent advancements in cancer care, coupled with early detection and an aging
      population have resulted in significant growth of cancer survivors. Long term
      follow up of such survivors is essential given the heightened risk for
      development of late effects such as secondary neoplasms, cardiovascular disease
      or psychosocial dysfunction among others. As more patients with hematologic
      malignancies are cured or managed over protracted periods of time, awareness of
      such issues is paramount for the practicing clinicians for optimal patient
      management. In this review, we describe the genesis of the field of cancer
      survivorship, and then it's gentle metamorphosis into multiple sub-fields
      currently by presenting literature relevant to late effects commonly seen in
      Hodgkin lymphoma, non-Hodgkin lymphoma, chronic leukemia and multiple myeloma. We
      will discuss the strengths and pitfalls of the existing models of survivorship
      care in hematologic malignancies and conclude with expert perspective on how to
      move the field forward.

PMID- 30093157
TI  - Transforming growth factor-beta 1 polymorphisms and anti-tuberculosis drug
      induced liver injury. Polymorphisms in TGFbeta1 and its relationship with anti
      tuberculosis drug-induced liver injury.
AB  - AIM: There is evidence to suggest that transforming growth factor-beta 1 takes
      part in a series of physiological and pathological processes in the human body,
      including wound healing, tissue fibrosis and embryonic development. We
      hypothesized that polymorphisms in the transforming growth factor-beta 1 gene
      single nucleotide polymorphisms (SNPs) were associated with anti-tuberculosis
      drug-induced liver injury (ATLI). METHODS: In a prospective study, 280 newly
      diagnosed tuberculosis patients were followed up for three months after
      initiating anti-tuberculosis therapy. Tag-SNPs of transforming growth factor-beta
      1 were genotyped with the MassARRAY platform. The associations between SNPs and
      ATLI were analyzed by logistic regression analysis adjusting for confounding
      factors. RESULTS: Of the 280 patients recruited in this study, 33 were excluded
      during the three months of follow-up, and 24 were diagnosed with ATLI and were
      considered as the ATLI group. The remaining 223 subjects without ATLI were
      considered as the non-ATLI group. After correction for potential confounding
      factors using a multivariate logistic regression analysis, we found that the
      frequencies of polymorphisms and haplotypes of transforming growth factor-beta 1
      were similar in patients with ATLI and without ATLI. CONCLUSION: The present
      results suggest that transforming growth factor-beta 1 polymorphisms do not play
      essential roles in the pathogenesis of ATLI in Chinese patients.

PMID- 30093159
TI  - New High Blood Pressure Guidelines: Back on Track With Lower Treatment Goals, but
      Implementation Challenges Abound.
AB  - The recently released 2017 High Blood Pressure Guidelines depart from past
      guidelines in both their approach and recommendations. Developed by multiple
      health organizations, including the American College of Preventive Medicine, the
      guidelines continue to define normal blood pressure as <120/80 mmHg, but now
      define hypertension as >=130/80 mmHg (previously >=140/90 mmHg). This change
      categorizes 101 million Americans (46% of adults) as hypertensive (compared to
      32% previously). The guidelines rely heavily on findings from the Systolic Blood
      Pressure Intervention Trial (SPRINT). This clinical trial demonstrated
      substantial reductions in key adverse outcomes from intensive blood pressure
      management (goal systolic blood pressure <120 mmHg) compared to standard
      treatment (<140 mmHg). The guidelines emphasize non-drug strategies for blood
      pressure management, particularly healthy diet, several forms of physical
      activity, reduction in sodium intake, enhancement of potassium intake, reduction
      in alcohol use, and weight loss. A risk-based approach is recommended for drug
      therapy. Individuals with an elevated 10-year risk of future cardiovascular
      disease events should receive drug therapies for blood pressures >=130/80 mmHg,
      whereas those at lower risk should receive antihypertensive medications for blood
      pressures >=140/90 mmHg. Given that high blood pressure is poorly managed even
      with easier-to-reach goals, effective implementation of the guidelines will
      present significant challenges. The guidelines suggest that successful
      implementation requires the adoption of new models of chronic disease care,
      including team-based care, telehealth, a shift towards self-management, better
      approaches to patient adherence, and use of home blood pressure monitoring.
      Attention to systems level issues is much needed, including population-based
      management, aligned financial incentives, improved health literacy, community
      interventions, and improved access to primary care and medications.

PMID- 30093160
TI  - Immunotolerant children with chronic hepatitis B - To treat or not - The dilemma
      continues.

PMID- 30093156
TI  - Influence of biomass burning on atmospheric aerosols over the western South China
      Sea: Insights from ions, carbonaceous fractions and stable carbon isotope ratios.
AB  - Total suspended particle (TSP) samples were collected during a cruise campaign
      over the western South China Sea (SCS) from August to September 2014. Ten water
      soluble ions (WSI), organic carbon (OC), elemental carbon (EC) and stable carbon
      isotope ratios of total carbon (delta13CTC) were measured. The average
      concentrations of total WSI, OC and EC were 7.91 +/- 3.44 MUg/m3, 2.04 +/- 1.25
      MUg/m3 and 0.30 +/- 0.22 MUg/m3, respectively. Among the investigated WSI,
      sulfate (SO42-), sodium (Na+) and chloride (Cl-) were the most abundant species,
      accounting for 39.2%, 24.5% and 14.3% of the total mass of the WSI, respectively.
      Significantly positive correlations of OC and EC with non-sea-salt potassium (nss
      K+), a tracer for biomass burning, suggest that biomass burning is the major
      source of carbonaceous aerosols. The values of delta13CTC ranged from -26.60/00
      to -24.40/00 with an average of -25.3 +/- 0.70/00. Based on the literature data
      of delta13CTC, back-trajectory analysis and satellite fire spots, we propose that
      C3 plant burning in Southeast Asia significantly contributes to carbonaceous
      aerosols over the western SCS. This is also supported by a good correlation
      between delta13CTC and the mass ratios of nss-K+/TC. Furthermore, high Cl-
      depletion (73 +/- 23%) was observed in the aerosols over the western SCS. Given
      the neutralization of SO42- by ammonium (NH4+), excess nss-SO42- and oxalate
      (C2O42-) made major contributions to Cl- depletion in the samples strongly
      influenced by biomass burning. This study provides useful information to better
      understand the influence of biomass burning on atmospheric aerosols over the SCS.

PMID- 30093161
TI  - Clinical use of dendritic cell-derived exosomes for hepatocellular carcinoma
      immunotherapy: How far we are?

PMID- 30093162
TI  - Mortality due to immunotherapy related hepatitis.

PMID- 30093163
TI  - Examination of clinical and psychosocial determinants of exercise capacity change
      in cardiac rehabilitation.
AB  - PURPOSE: Most cardiac rehabilitation (CR) completers improve in multiple
      functional and psychosocial domains. However, not all demonstrate uniform
      improvement in functional indicators such as exercise capacity. This study
      examined baseline predictors and correlates of change in exercise capacity from
      CR intake to completion. METHODS: CR participants (n = 488) completed assessment
      of metabolic equivalents (METs) via treadmill stress test, depressive symptoms,
      quality of life, and social support at intake and discharge. Associations between
      demographic, clinical, and psychosocial factors and MET changes was tested with
      linear regression. RESULTS: METs increased from intake to discharge (1.91 +/-
      1.48, p < .001). Younger age (p < .001), lower BMI (p < .001), and lower weight
      (p < .01) were associated with greater MET change. Greater percentage weight loss
      (p < .05), and self-reported improvements in physical functioning (p < .001) and
      bodily pain (p < .01) were concurrently related to MET change. CONCLUSIONS: Older
      CR attendees and those with higher baseline BMI may benefit from tailored
      intervention to ensure maximum benefit in exercise capacity.

PMID- 30093164
TI  - Age and pain as predictors of discomfort in patients undergoing transfemoral
      percutaneous coronary interventions.
AB  - BACKGROUND: Transfemoral percutaneous coronary intervention (PCI) requires strict
      bed rest, causing pain and discomfort in patients. However, no studies have
      investigated this issue. OBJECTIVES: To investigate the predictors of discomfort
      in transfemoral PCI patients. METHODS: A cross-sectional sample of 110 patients
      from two coronary care units completed questionnaires on demographic and clinical
      characteristics, visual analogue pain scale, and discomfort. RESULTS: Eight
      factors predicted overall discomfort: physiologic pain, physiological discomfort,
      psychological discomfort, analgesic use after sheath removal, hemostasis method,
      and bed rest duration. Psychological discomfort was associated with age, chronic
      obstructive pulmonary disease, analgesic use after sheath removal, successful
      hemostasis, and hematoma >5 cm. A hierarchical regression model explained 70.5%
      of the variance in overall discomfort. CONCLUSIONS: Age and physiologic pain are
      major predictors of overall discomfort, especially in patients aged <60 years
      having high pain sensitivity. Critical care providers should note patients'
      physiological and psychological issues throughout the PCI process.

PMID- 30093165
TI  - Human papillomavirus and nonhuman papillomavirus pathways to vulvar squamous cell
      carcinoma: A review.
AB  - Vulvar squamous cell carcinoma (VSCC) is a rare tumor of the female genital
      tract. While previously considered a disease of older women, the epidemiologic
      landscape is changing with more young women diagnosed with VSCC and its precursor
      lesions. This may be secondary to the global increase in human papillomavirus
      (HPV) infection of the lower genital tract. While VSCC precursor lesions have
      been described for many years, the terminology, and thus the understanding and
      reproducibility of these lesions have been debated. In the most recent
      publication from the International Society of the Study of Vulvovaginal Disease
      (ISSVD), there is a distinction between high-risk vulvar lesions associated with
      HPV infection (vulvar HSIL) and high-risk vulvar lesions that are not thought to
      be associated with HPV infection (differentiated VIN or dVIN). These precursors
      have different risk factors and thus affect different populations, leading to two
      separate pathways for developing VSCC. The HPV-related VSCC is likely to have a
      better prognosis than the non-HPV-related VSCC, as seen in other disease sites.
      Early-stage VSCC may be surgically treated with margin and node status affecting
      whether adjuvant radiation is recommended. Advanced stage VSCC may be
      unresectable, requiring neoadjuvant chemoradiation. Although VSCC is a rare
      disease, ongoing studies investigating the different pathways leading to
      carcinogenesis may increase the understanding of VSCC and improve therapeutic
      options for patients.

PMID- 30093166
TI  - Acoustic Voice Analysis and Maximum Phonation Time in Relation to Voice Handicap
      Index Score and Larynx Disease.
AB  - OBJECTIVES: Patients with voice-related disorders are ideally treated by a
      multidisciplinary team. Acoustic voice analysis and patient-reported outcome
      measures are recommended parts of the clinical assessment. The present paper aims
      at further documenting the importance of acoustic voice analyses, maximum
      phonation time (MPT) and Voice Handicap Index (VHI) into clinical investigations.
      STUDY DESIGN: The participants (N = 80 larynx cancer, N = 32 recurrent palsy, N =
      23 dysfunctional, N = 75 degenerative/inflammation (N = 19 various excluded))
      were included consecutively at the outpatient laryngology clinic at Haukeland
      University Hospital. In addition, a control group of 98 healthy subjects were
      included. METHOD: Voice samples, MPT, and the VHI scores in addition to standard
      clinical information were obtained. Acoustic analyses were performed from these
      samples determining level of jitter, shimmer and Noise-to-Harmonic ratio (NHR) as
      well as analyzing frequency of a prolonged vowel. RESULTS: Jitter, shimmer, and
      NHR scores correlated strongly (r ~ 0.8; P < 0.001) to each other. By Analysis of
      Variance analyses, we have determined significant dependence on diagnostic group
      analyzing all the obtained acoustic scores (all P < 0.001). All patient groups
      but the dysfunctional group scored to some extent worse than the control group
      (mostly at P < 0.001). In addition, jitter scores from dysfunction group were
      lower than recurrent palsy group (P < 0.05) and shimmer scores were lower among
      dysfunctional than the cancer group (P < 0.05). Regarding NHR the cancer patients
      scored higher than the degenerative/inflammatory group (P < 0.05). The cancer
      group scored with longer MPT than the degenerative/inflammatory (P < 0.001) and
      recurrent palsy groups (P < 0.05). CONCLUSION: Among larynx disease patients
      acoustic and MPT analyses segregated with all determined analyses between
      patients and control conditions except the dysfunctional group, but also to some
      extent between various patient groups. VHI scores correlated to jitter, shimmer
      and NHR scores among cancer and degenerative/inflammatory disease patients.
      Acoustic analyses potentially add information useful to laryngological patient
      studies.

PMID- 30093167
TI  - Novel Uses of Point-of-Care Ultrasound for Pediatric Foreign Bodies: An Emergency
      Department Case Series.
AB  - BACKGROUND: Foreign bodies (FBs) are a diagnostic challenge to pediatric
      emergency providers. Point-of-care ultrasound (POCUS) is an important adjunct to
      the diagnostic pathway of children with suspected FBs. CASE REPORT: This case
      series describes three examples of novel extended ultrasonography uses in the
      pediatric emergency department for the detection of FBs involving different organ
      systems (i.e., abdominal, esophageal, and scrotal). WHY SHOULD AN EMERGENCY
      PHYSICIAN BE AWARE OF THIS?: FBs are a diagnostic challenge to pediatric
      emergency providers. POCUS should be recognized as an important adjunct to the
      diagnostic pathway of children with suspected FBs. When used thoughtfully, it can
      narrow the differential diagnosis, guide further confirmatory investigations,
      reduce cognitive burden, and tailor downstream patient care.

PMID- 30093168
TI  - A Patient With Hereditary ATTR and a Novel AGel p.Ala578Pro Amyloidosis.
AB  - Hereditary amyloidosis represents a group of diseases in which mutant proteins
      are deposited in various organs leading to their dysfunction. Correct
      identification of the amyloid-causing protein is critical because this will
      determine the optimal therapy for the patient. The most common type of hereditary
      amyloidosis is due to mutant transthyretin (ATTRm) deposition and often presents
      with heart failure or peripheral neuropathy. We report the first known case of a
      patient who had amyloidosis both due to a mutant transthyretin (p.Val122Ile) and
      due to a novel variant in the gelsolin gene (p.Ala578Pro). Both mutant proteins
      were identified by mass spectrometry analysis of amyloid deposits as well as
      sequencing of the genes. Molecular dynamic simulations suggest that the gelsolin
      p.Ala578Pro variant is likely amyloidogenic.

PMID- 30093169
TI  - Family History of Cardiovascular Disease: How Detailed Should It Be?

PMID- 30093170
TI  - Contemporary approach to the patent ductus arteriosus and future considerations.

PMID- 30093171
TI  - 3-D Neural denoising for low-dose Coronary CT Angiography (CCTA).
AB  - CCTA has become an important tool for coronary arteries assessment in low and
      medium risk patients. However, it exposes the patient to significant radiation
      doses, resulting from high image quality requirements and acquisitions at
      multiple cardiac phases. For widespread use of CCTA for coronary assessment,
      significant reduction of radiation exposure with minimal image quality loss is
      still needed. A neural denoising scheme, relying on a fully convolutional neural
      network (FCNN) architecture, is developed and applied to noisy CCTA. In contrast
      to previously published methods, the proposed FCNN is trained directly on 3-D CT
      data patches (blocks), implementing 3-D convolutions. Considering that anatomy is
      inherently tridimensional, the proposed 3-D approach may better capture and
      enforce inter-slice continuity of tiny structures. While training is performed on
      individual blocks, whole input scans can be fed and denoised in one piece, thus
      leveraging the fully convolutional architecture to maximize processing speed. The
      proposed method is compared to state-of-the-art denoising algorithms on a dataset
      of 45 CCTA scans. Low-dose scans are simulated by synthetic Poisson noise applied
      to the sinogram corresponding to a 90% reduction in radiation dose. The average
      feature similarity score (0.864) and the peak signal-to-noise ratio (41.47)
      obtained for the proposed algorithm outperformed the compared methods while
      requiring significantly shorter processing time. A set of 2-D FCNNs, structurally
      similar to the proposed 3-D network, are also implemented to demonstrate
      contribution of the additional dimension to the improved denoising. For further
      validation of the method coronary reconstruction using the Intellispace cardiac
      tool (Philips, Holland) is performed both on a real noisy CCTA scan and on the
      denoised scan using the proposed method. It is shown that the cardiac tool
      succeeds in reconstructing more coronaries using the scan denoised by the
      proposed method. The obtained results suggest the proposed method provides an
      efficient and powerful approach to low-dose CCTA denoising.

PMID- 30093172
TI  - Prostate Cancer Grading: Are We Heading Towards Grade Grouping Version 2?

PMID- 30093173
TI  - Re: Isabel Rauscher, Charlotte Duwel, Bernhard Haller, et al. Efficacy,
      Predictive Factors, and Prediction Nomograms for 68Ga-labeled Prostate-specific
      Membrane Antigen-ligand Positron-emission Tomography/Computed Tomography in Early
      Biochemical Recurrent Prostate Cancer After Radical Prostatectomy. Eur Urol
      2018;73:656-61: Clinical Significance of Prostate-specific Membrane Antigen
      Immunohistochemistry and Role of the Uropathologists.

PMID- 30093174
TI  - Sweet taste potentiates the reinforcing effects of e-cigarettes.
AB  - Electronic cigarettes (e-cigarettes) are becoming increasingly popular. The
      popularity of fruit flavors among e-cigarette users suggests that sweet taste may
      contribute to e-cigarette appeal. We therefore tested whether sweet taste
      potentiates the reinforcing effects of nicotine. Using a conditioning paradigm
      adapted to study e-cigarettes, we tested whether exposure to flavored e
      cigarettes containing nicotine plus sweet taste would be more reinforcing than
      unsweetened e-cigarettes. Sixteen light cigarette smokers smoked 4 distinctly
      colored e-cigarettes containing sweetened and unsweetened flavors with or without
      nicotine for 2 days each. Brain response was then assessed to the sight and smell
      of the 4 exposed e-cigarettes using fMRI. After exposure, sweet-paired flavors
      were wanted (p = .024) and tended to be liked (p = .053) more than nicotine
      paired flavors. Moreover, sweet taste supra-additively increased liking for
      nicotine-paired flavors in individuals who did not show increased liking for
      nicotine alone (r = -.67, p = .005). Accordingly, cues predicting sweet compared
      to non-sweet flavors elicited a stronger response in the nucleus accumbens (NAcc,
      pSVC = .050) and the magnitude of response to the sight (pSVC = .022) and smell
      (pSVC = .017) of the e-cigarettes correlated with changes in liking. By contrast,
      the sight and smell of cues predicting nicotine alone failed to elicit NAcc
      response. However, the sight and smell of e-cigarettes paired with sweet+nicotine
      (pSVC = .035) produced supra-additive NAcc responses. Collectively, these
      findings demonstrate that sweet taste potentiates the reinforcing effects of
      nicotine in e-cigarettes resulting in heightened brain cue-reactivity.

PMID- 30093175
TI  - Report of the international conference on next generation sequencing for
      adventitious virus detection in biologicals.
AB  - A fundamental aspect of biological product safety is to assure absence of
      adventitious agents in the final product. Next-generation or high-throughput
      sequencing (NGS/HTS) has recently demonstrated detection of viruses that were
      previously missed using the recommended routine assays for adventitious agent
      testing of biological products. This meeting was co-organized by the
      International Alliance for Biological Standardization (IABS) and the U.S. Food
      and Drug Administration (FDA) to assess the current status and discuss the
      readiness of NGS for adventitious virus detection in biologics. The presentations
      included efforts for standardization, case studies on applications in biologics,
      comparison with routine virus detection assays, and current regulatory thinking.
      Participants identified the need for standard reference reagents, well-annotated
      databases, large data storage and transfer capacity, personnel with relevant
      expertise, particularly in bioinformatics; and harmonization of international
      regulations for testing biologic products and reagents used for their
      manufacturing. We hope this meeting summary will be of value to regulators and
      industry for considerations of NGS applications for adventitious virus detection
      in biologics.

PMID- 30093176
TI  - Editor's Choice - Impact of Comorbidity, Medication, and Gender on Amputation
      Rate Following Revascularisation for Chronic Limb Threatening Ischaemia.
AB  - OBJECTIVE/BACKGROUND: Chronic limb threatening ischaemia (CLTI) has a high risk
      of amputation and mortality. Increased knowledge on how sex, comorbidities, and
      medication influence these outcomes after revascularisation may help optimise
      results and patient selection. METHODS: This population based observational
      cohort study included all individuals revascularised for CLTI in Sweden during a
      five year period (10,617 patients in total). Data were retrieved and merged from
      mandatory national healthcare registries, and specifics on amputations were
      validated with individual medical records. RESULTS: Mean age at revascularisation
      was 76.8 years. Median follow up was 2.7 years (range 0-6.6 years). Male sex
      (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.33), renal
      insufficiency (HR 1.57, 95% CI 1.32-1.87), diabetes (HR 1.45, 95% CI 1.32-1.60),
      and heart failure (HR 1.17, 95% CI 1.05-1.31) were independently associated with
      an increased amputation rate, whereas the use of statins (HR 0.71, 95% CI 0.64
      0.78) and low dose acetylsalicylic acid (HR 0.77, 95% CI 0.70-0.86) were
      associated with a reduced amputation rate. For the combined end point of
      amputation or death, an association with increased rates was found for male sex
      (HR 1.25, 95% CI 1.18-1.32), renal insufficiency (HR 1.94, 95% CI 1.75-2.14),
      heart failure (HR 1.50, 95% CI 1.40-1.60), and diabetes (HR 1.31, 95% CI 1.23
      1.38). The use of statins (HR 0.74, 95% CI 0.67-0.82) and low dose
      acetylsalicylic acid (HR 0.82, 95% CI 0.77-0.88]) were related to a reduced risk
      of amputation or death. CONCLUSIONS: Renal insufficiency is the strongest
      independent risk factor for both amputation and amputation/death in
      revascularised CLTI patients, followed by diabetes and heart failure. Men with
      CLTI have worse outcomes than women. These results may help govern patient
      selection for revascularisation procedures. Statin and low dose acetylsalicylic
      acid are associated with an improved limb outcome. This underlines the importance
      of preventive medication to reduce general cardiovascular risk and increase limb
      salvage.

PMID- 30093177
TI  - Failure to Rescue for Abdominal Aortic Aneurysm Surgery - An Enigma Explained?

PMID- 30093178
TI  - ERRATUM.

PMID- 30093179
TI  - Incidence of infantile spinal muscular atrophy on Shikoku Island of Japan.
AB  - BACKGROUND: Spinal muscular atrophy (SMA) is an autosomal recessive disorder
      caused by homozygous mutations in the SMN1 gene. SMA has long been known to be
      the most common genetic cause of infant mortality. However, there have been no
      reports on the epidemiology of infantile SMA (types 1 and 2) based on genetic
      testing in Japan. In this study, we estimated the incidence of infantile SMA on
      Shikoku Island, which is a main island of Japan and consists of four prefectures:
      Ehime, Kagawa, Tokushima and Kochi. METHODS: A questionnaire was sent to 91
      hospitals on Shikoku Island to investigate the number of SMA infants born from
      2011 to 2015. A second questionnaire was then sent to confirm the diagnoses of
      SMA based on clinical and genetic features. RESULTS: Responses were received from
      all of the hospitals, and four patients were diagnosed with infantile SMA among
      147,950 live births. We estimated the incidence of infantile SMA patients as 2.7
      per 100,000 live births (95% confidence interval, 0.1-5.4). A comparison of the
      four prefectures indicated that the incidence of infantile SMA was significantly
      higher in Ehime Prefecture than in the other three prefectures; 5.6 per 100,000
      live births (95% confidence interval, -0.7 to 11.9) in Ehime Prefecture and 1.1
      per 100,000 live births (95% confidence interval, -1.0 to 3.1) in the other
      prefectures. CONCLUSION: We estimated the incidence of infantile SMA in an
      isolated area of Japan. For more precise determination of the incidence of
      infantile SMA, further studies that include neonatal screening will be needed.

PMID- 30093180
TI  - Comparison of pediatric post-reduction fluoroscopic- and ultrasound forearm
      fracture images.
AB  - OBJECTIVE: Emergency department (ED) reduction of pediatric fractures occurs most
      commonly in the forearm and can be challenging if fluoroscopy is not available.
      We sought to assess the ability of point of-care ultrasonography (POCUS) to
      predict adequacy of reduction by fluoroscopy. METHODS: We prospectively enrolled
      ED patients 0-17 years of age with radial and/or ulnar fractures requiring
      reduction under fluoroscopic guidance. Post-reduction POCUS (probe dorsal, volar,
      and coronal) and fluoroscopic (AP and lateral) fracture images were recorded.
      Fracture angles were compared between blinded POCUS and fluoroscopic measurements
      and between POCUS measurements by a blinded emergency physician and a blinded
      radiologist, reporting mean differences and 95% confidence intervals. We
      calculated sensitivity, specificity, and likelihood ratios of POCUS in the
      prediction of fluoroscopically detected post-reduction malalignment, as
      interpreted by a blinded pediatric orthopaedist. RESULTS: The 58 patients were
      7.9 +/- 3.5 years of age and had 21 radial (36%), 1 ulnar (2%), and 36 radioulnar
      (62%) fractures. Fluoroscopy and POCUS angles were within a mean of 0.1 degrees 
      3.2 degrees , depending on the site and surface measured. Radiologist- and
      emergency physician-interpreted POCUS measurements were within a mean of 1
      degrees  in all dimensions. POCUS identified inadequate reductions with 100%
      sensitivity and 92-93% specificity. CONCLUSIONS: Blinded emergency medicine and
      radiology interpretations of post-reduction POCUS fracture images agree closely.
      Post-reduction POCUS measurements are comparable to those obtained by fluoroscopy
      and accurately predict adequacy of reduction. POCUS can be used to guide
      pediatric fracture reduction when bedside fluoroscopy is not available in the ED.

PMID- 30093181
TI  - Re: Open reduction and internal fixation of palatal fractures using three
      dimensional plates.

PMID- 30093182
TI  - Solid malignant metastases in the jaw bones.
AB  - Metastatic tumours to the jaw bones are rare, and usually develop during the
      final stages of cancer. Some, such as those of lung, breast, and kidney, are more
      likely to metastasise to the jaw. We have therefore analysed the clinical and
      epidemiological characteristics of patients with metastatic tumours. We retrieved
      the notes of 4 478 patients with metastatic tumours to the jawbones who were
      treated in the Clinical Hospital Centre Dubrava in Zagreb, Croatia, during the 15
      years 2002-17 and made a retrospective analysis of patients' age, sex, site of
      primary tumour, site and clinical presentation of the metastases, time interval
      since diagnosis of the primary tumour and oral metastases, and time interval from
      diagnosis of oral metastases to death. Of the 10 who were diagnosed with
      metastases to the jaw, there were four male and six female patients (mean age 57
      (range 51-84) years) and the most common primary tumours were kidney (n=5), lung
      (n=2), breast (n=1), colon (n=1) and unknown (n=1). The mandible was more often
      affected (n=7) than the maxilla (n=3), and the most common histological type was
      adenocarcinoma (n=6). The primary tumour in most of the patients (n=7) was
      diagnosed before the oral metastatic lesion. A metastasis in the jaw was the
      first sign of metastatic tumour in three patients, and in one case the metastasis
      and the primary tumour were diagnosed at the same time. Most of the patients had
      some oral problems. The time intervals from diagnosis of an oral metastasis to
      death varied from one month - five years. Because of the rarity of the
      presentation, the diagnosis of an oral metastatic lesion remains challenging, so
      metastases in the jaw should be suspected in every patient with such cancers and
      lesions in the jaw.

PMID- 30093183
TI  - Re: re: Open reduction and internal fixation of palatal fractures using three
      dimensional plates.

PMID- 30093184
TI  - Dermoscopy beyond dermatology: evaluating its use in plastic and oral and
      maxillofacial surgery.

PMID- 30093185
TI  - Injury to the oral mucosa by organophosphates without systemic toxicity: a rare
      case.
AB  - We describe a case of multiple Zargar grade IIA ulcerations of the oral mucosa
      with no systemic toxicity in a patient after ingestion of an organophosphate.
      Serial debridement, control of superadded infections, and active physiotherapy
      were the mainstay of the treatment plan. We know of no other reported cases of
      poisoning by organophosphates that caused burns of the oral mucosa and no
      systemic toxicity.

PMID- 30093186
TI  - Transesophageal Echocardiographic Evaluation of a Double Orifice Mitral Valve.
AB  - Intraoperative transesophageal echocardiography currently is used routinely for
      many cardiothoracic surgical procedures. Although it is often used for
      intraoperative cardiac monitoring and to confirm preoperative echocardiographic
      findings, it may sometimes result in the discovery of unexpected pathology. In
      this e-challenge, a patient was found to have a mitral valve abnormality that was
      not previously detected on the preoperative transthoracic echocardiogram. The
      mitral valve anomaly subsequently was evaluated to characterize the anatomy,
      interrogate the valve, and provide a diagnosis.

PMID- 30093187
TI  - Understanding Echo Through Embryology.

PMID- 30093188
TI  - The Effects of Secondhand Smoke Exposure on Postoperative Pain and Ventilation
      Values During One-Lung Ventilation: A Prospective Clinical Trial.
AB  - OBJECTIVES: To investigate the relationships between secondhand smoke (SHS)
      exposure and oxygenation during one-lung ventilation (OLV) in lobectomy surgery
      and between SHS exposure and postoperative analgesic consumption. DESIGN:
      Prospective study. SETTING: University, Faculty of Medicine, operating room.
      PARTICIPANTS: Sixty adult patients with American Society of Anesthesiologists
      score II to III, aged 18 to 65 years, with a body mass index (BMI) <35 kg/m2
      scheduled for lobectomy surgery by open thoracotomy. INTERVENTIONS: Patients were
      divided into 2 groups: the SHS group (n = 30) (urine cotinine level >=6.0 ng/mL)
      and the NS (nonsmoker) group (n = 30) (urine cotinine level <6.0 ng/mL and no
      smoking history). SHS exposure was defined according to a previously published
      algorithm. MEASUREMENTS AND MAIN RESULTS: Noninvasive blood pressure,
      electrocardiography, capnography, and peripheral oxygen saturation were
      monitored, and intra- and postoperative arterial oxygen tension (PaO2), arterial
      carbon dioxide tension (PaCO2), and intraoperative peak airway pressure were
      compared between the 2 groups. Postoperative analgesic consumption was
      calculated. No significant differences in demographics or preoperative data were
      noted between the 2 groups. PaO2 values 10 minutes after OLV onset and 10 minutes
      after the end of OLV were increased significantly in the NS group compared with
      those in the SHS group (p < 0.05). PaO2 values after 10 minutes of OLV in the NS
      and SHS groups were 285.5 +/- 90 mmHg and 186.7 +/- 66 mmHg, respectively. PaO2
      values after OLV termination in the NS and SHS groups were 365.8 +/- 58 mmHg and
      283.6 +/- 64 mmHg (p < 0.05), respectively. PaCO2 values 10 minutes after OLV
      onset, 10 minutes after the end of OLV, at the end of surgery, and upon arrival
      in the intermediate care unit were significantly different between the 2 groups
      (p < 0.05). CONCLUSION: The present study demonstrated that during OLV, patients
      exposed to SHS exhibited significantly lower arterial oxygen pressure compared
      with nonsmokers. Arterial carbon dioxide values were increased significantly in
      SHS-exposed patients. Morphine consumption for postoperative analgesia also was
      increased in patients exposed to SHS compared with that in nonsmokers.

PMID- 30093189
TI  - Fast-Track Cardiac Anesthesia for Transthoracic Device Closure of Perimembranous
      Ventricular Septal Defects in Children: A Single Chinese Cardiac Center
      Experience.

PMID- 30093190
TI  - Erector Spinae Plane Block for Postoperative Rescue Analgesia in Thoracoscopic
      Surgery.

PMID- 30093191
TI  - Burnout Among Anesthesiologists: It's Time for Action!

PMID- 30093192
TI  - Impella RP in the Treatment of Right Ventricular Failure: What We Know and Where
      We Go.
AB  - Temporary mechanical circulatory support devices for the treatment of acute right
      ventricular failure represent crucial tools for clinical practice. Right
      ventricular failure presents specific treatment issues, and dedicated
      percutaneous devices are less in number compared to the left ventricle. Current
      data and insights on mechanical circulatory support for the right ventricle come
      mostly from the context of cardiac surgery, predominantly the setting of acute
      right ventricular failure after left ventricular assist device implantation. The
      Impella RP (Abiomed, Danvers, MA) is a minimally invasive temporary device that
      has gained application for the percutaneous treatment of right ventricular
      failure with positive clinical results. Even though treatment indications are
      clear, technical and management issues still are relevant because of the limited
      scientific data available. Appropriate positioning and repositioning, interaction
      with right ventricular valvular apparatus, anticoagulation management, weaning,
      and patient mobilization are examples of the open challenges. In line with the
      positive initial experience with this device, future research efforts should be
      focused on the improvement of device limitations and on providing additional data
      that might drive optimal clinical management.

PMID- 30093193
TI  - A Case of Adult-onset Pompe Disease with Cerebral Stroke and Left Ventricular
      Hypertrophy.
AB  - BACKGROUND: Pompe disease is an autosomal recessive glycogen storage disorder
      caused by a deficiency of the lysosomal glycogen-hydrolyzing enzyme acid alpha
      glucosidase. The adult-onset form, late-onset Pompe disease, has been
      characterized by glycogen accumulation, primarily in skeletal and smooth muscles,
      causing weakness of the proximal limb girdle and respiratory compromises. CASE
      REPORT: A 59-year-old female was admitted to the hospital with acute cerebral
      stroke at the age of 57years. Following her admission, conventional conservative
      stroke management followed by cerebral arterial clipping was performed. However,
      weakness of lower extremities, predominantly in the right side, and evening
      headache were persisting. After obtaining a careful past history, she noticed
      that she had a history of recurrent respiratory tract infection and she did not
      like any physical exercise in school. She also complained of gait disturbance
      since 32years of age. She had also been suffering from systemic hypertension
      since 40years of age. She had mild respiratory and swallowing difficulties. Her
      brain Magnetic Resonance (MR) revealed multiple infractions and white matter
      degeneration with irregular basilar arterial walls. A computed tomography (CT)
      scan of lower extremities showed diffuse fibrosis of the proximal muscles
      predominantly on the right thigh. Cardiac echocardiogram showed left ventricular
      hypertrophy. Electron microscopy of blood cells including lymphocytes and
      platelets and skin fibroblasts showed marked granular inclusions in lysosomes,
      suggesting glycogen accumulation. Her measured acid alpha-glucosidase activity
      was very low, 1.3 pmol hour-1 punch-1, and we found a homozygous splice-site
      mutation c.546G>T in the GAA gene. CONCLUSION: Cerebral stoke as an initial
      finding for an adult-type Pompe disease is rare. Left ventricular hypertrophy is
      also rarely reported for adult onset of Pompe disease. This case will explore
      further ways to diagnose adult-onset Pompe disease.

PMID- 30093194
TI  - Transferring Stroke Knowledge from Children to Parents: A Systematic Review and
      Meta-Analysis of Community Stroke Educational Programs.
AB  - BACKGROUND: The purpose of this systematic review and meta-analysis on child-to
      parent communication of stroke information (Child-Mediated Stroke Communication,
      CMSC) is to provide the highest levels of evidence supporting the role of this
      approach in community education. METHODS: Databases such as PubMed, Google
      Scholar, PsycINFO, Web of Science, MEDLINE, and CINHAL were searched to gather
      information on CMSC followed by a meta-analysis. The eligibility criteria were as
      follows: (a) children aged 9-15years and parents, (b) randomized or nonrandomized
      trials, and (c) outcome variables that included the proportions of parents
      answering the pretest and post-test on stroke knowledge regarding risk factors,
      symptoms, and what to do in the event of stroke. RESULTS: Of the 1668 retrieved
      studies, 9 articles were included. Meta-analytical findings yielded that the
      proportions of correct answers for stroke symptoms and its risk factors among
      parents were 0.686 (95% CI: 0.594-0.777) at baseline and increased to 0.847 (95%
      CI: 0.808-0.886) at immediate post-test and 0.845 (95% CI: 0.804-0.886) delayed
      post-test. The proportions of correct answers for behavioral intent to call 911
      when witnessing stroke was 0.712 (95% CI: 0.578-0.846) at baseline, rising to
      0.860 (95% CI: 0.767-0.953) at immediate post-test, and 0.846 (95% CI: 0.688
      1.004) at delayed post-test. CONCLUSIONS: CMSC is effective for educating
      families. More work is needed to increase the use of validated stroke literacy
      instruments and behavioral theory, and to reduce parental attrition in research
      studies.

PMID- 30093195
TI  - Cerebral Vasculopathy in Coarctation of Aorta-a Rare Association.
AB  - Coarctation of aorta is a rare congenital cardiovascular condition where patients
      are at risk of systemic arteriopathy, including hypertension and intracranial
      aneurysms.1 Here we report a rare case of young ischemic stroke, who was found to
      be having a cerebral vasculopathy and coarctation of aorta on evaluation.

PMID- 30093196
TI  - Sex Differences in Stroke Incidence in a Portuguese Community-Based Study.
AB  - BACKGROUND AND AIM: Stroke is a major health problem. Several studies reported
      sex differences regarding stroke. We aim to study this issue in an incidence
      stroke study. METHODS: Data were retrieved from a community-based prospective
      register of patients that had a first ever stroke in a life time between October
      2009 and September 2011. We studied sex differences regarding demographic data,
      vascular risk factors, stroke type, stroke severity (NIHSS), disability at 28days
      (modified Rankin scale (mRS)), and case fatality at 30 and 90days. RESULTS: From
      720 stroke patients, 45.3% were men. Women were older (75.0 +/- 13.6 versus 67.2
      +/- 14.9 years), had a worse premorbid mRS (39.3% versus 25.5%, P < .001), and a
      higher prevalence of hypertension (P = .004) and atrial fibrillation (P < .001).
      Previous myocardial infarction was more frequent in men (P = .001), as well as
      smoking habits (P < .001). Ischemic stroke was more common in women than men
      (87.6% versus 81.3%, P = .038). The 28 days' outcome was worse in women (mRS >=
      2, 77.2% versus 70.6%, P = .044). No differences were found in initial stroke
      severity (median NIHSS = 4) and case fatality at 30 and 90days, after adjusting
      for age and premorbid mRS. CONCLUSION: No differences were found in stroke
      initial severity and mortality at 30 and 90days between men and women, despite
      the sex differences pertaining to the stroke profile-age, vascular risk factors,
      stroke type, and outcome. Our results are somewhat discrepant from those
      described in the literature; more research is needed to understand if this may be
      due to changes in stroke standard of care.

PMID- 30093197
TI  - Atorvastatin Pretreatment Attenuates Ischemic Brain Edema by Suppressing
      Aquaporin 4.
AB  - BACKGROUND: Cerebral edema, a serious complication of acute cerebral infarction,
      has a crucial impact on morbidity and mortality in the early stage of cerebral
      infarction. And aquaporin 4 (AQP4), a bidirectional water transporting protein,
      plays a pivotal role in edema formation. At experimental model, it has proven
      that atorvastatin could exert pleiotropic neuroprotection on acute cerebral
      infarction independent of its cholesterol-lowering action. It was a common
      protective manifestation that atorvastatin can reduce the infarct volume and
      cerebral edema. However, little is known about atorvastatin improving ischemic
      brain edema by regulating AQP4 expression. This study intended to investigate the
      neuroprotection effects of atorvastatin pretreatment in rats with cerebral
      ischemia and further explore the potential relationship between atorvastatin and
      AQP4 expression. METHODS: Fifty-one adult male Sprague Dawley rats were randomly
      divided into 3 groups: sham, middle cerebral artery occlusion (MCAO), and
      atorvastatin pretreatment (Ator) group. For Ator group, 20 mg/kg of atorvastatin
      injectable suspension was administered once for 7days by gavage before operation,
      whereas the others were administered the same volume of saline matching. Except
      for sham group, MCAO and Ator groups were subjected to permanent MCAO by modified
      intraluminal suture method. Infarct volume, neurological deficit, brain water
      content (BWC), immunohistochemistry, western blot, and polymerase chain reaction
      (PCR) were measured at 24 hours after MCAO. RESULTS: Compared with sham group,
      the mNSS, infarct volume, and BWC of ischemic hemisphere were significantly
      increased (P < 0.001) in MCAO group. Positive cells and protein levels of p
      p38MAPK and AQP4 in peri-infarction were significantly increased (P < 0.01). The
      mRNA levels of p38MAPK and AQP4 were also prominently upregulated (P < 0.01).
      Interestingly, preadministration of atorvastatin dramatically decreased infarct
      volume and the BWC of ischemic hemisphere compared with MCAO group (P < 0.05).
      The overexpressions of p-p38MAPK and AQP4 in peri-infarction were significantly
      decreased (P < 0.05) and their mRNA levels were downregulated by atorvastatin
      pretreatment (P < 0.05). Neurological deficits were also dramatically improved (P
      < 0.001). CONCLUSION: To the best of our knowledge, this is the first study that
      demonstrates an effect of atorvastatin on expression of AQP4, and we propose that
      decreased AQP4 expression through a p38MAPK-suppression pathway may be the
      mechanism of atorvastatin alleviating ischemic cerebral edema.

PMID- 30093198
TI  - Right Hemisphere Contributions to Bilateral Force Control in Chronic Stroke: A
      Preliminary Report.
AB  - BACKGROUND: Bilateral motor control deficits poststroke may be lateralized by
      hemisphere damage. This preliminary study investigated bilateral force control
      between left and right hemisphere-damaged groups at baseline and after coupled
      bilateral movement training with neuromuscular stimulation. METHODS: Stroke
      participants (8 left hemisphere and 6 right hemisphere cerebrovascular accidents)
      performed a bilateral isometric force control task at 3 submaximal force levels
      (5%, 25%, and 50% of maximum voluntary contraction [MVC]) before and after
      training. Force accuracy, force variability, and interlimb force coordination
      were analyzed in 3-way mixed design ANOVAs (2 * 2 * 3; Group * Test Session *
      Force Level) with repeated measures on test session and force level. RESULTS: The
      findings indicated that force accuracy and variability at 50% of MVC in the right
      hemisphere-damaged group were more impaired than lower targeted force levels at
      baseline, and the impairment at the highest target level was improved after
      coupled bilateral movement training. However, these patterns were not observed in
      the left hemisphere-damaged group. CONCLUSIONS: Current findings support a
      proposition that the right hemisphere presumably contributes to controlling
      bilateral force production.

PMID- 30093199
TI  - Cerebral Microbleeds are Associated with Higher Mortality Among Ischemic Stroke
      Patients.
AB  - BACKGROUND: Several studies have shown that cerebral microbleeds (CMBs) increase
      the risk of long-term stroke-related mortality. The purpose of this study was to
      determine if the existence and burden of CMBs are a predictor of in-hospital
      death among patients with acute ischemic stroke (AIS). METHODS: We studied
      consecutive ischemic stroke patients who admitted to our tertiary center over a 2
      year period (2013-2014). Patients who underwent thrombolysis were excluded.
      Baseline characteristics of patients, number and topography of CMBs, white matter
      lesions, and spontaneous symptomatic hemorrhagic transformation were recorded.
      Outcome measure in our study was in-hospital death. RESULTS: Out of 1126
      consecutive AIS patients evaluated in this study, 772 patients included in the
      study (mean age 61.9 +/- 14.2years [18-95 years], 51.6% men, and 58.2% African
      American). CMBs were present on the magnetic resonance imaging (MRI) sequences of
      124 (16.1%) patients. The overall rate of in-hospital mortality was 4.1%. The
      presence or absence of CMBs was not predictive of in-hospital mortality (P =
      .058). After adjusting for potential confounders, the presence of >=4 CMBs on T2*
      weighted MRI was independently (P = .004) associated with a higher likelihood of
      in-hospital death (odds ratio: 6.6, 95% confidential interval: 2.50 and 17.46) in
      multivariable logistic regression analyses. Older age, higher National Institute
      of Health stroke scale, and history of atrial fibrillation were also associated
      with greater chance of in-hospital death. CONCLUSIONS: The presence or absence of
      CMBs was not predictive of in-hospital mortality. However, the presence of
      multiple CMBs was associated with a higher in-hospital mortality rate among AIS
      patients.

PMID- 30093200
TI  - Low Body Mass Index is a Poor Prognosis Factor in Cardioembolic Stroke Patients
      with NonValvular Atrial Fibrillation.
AB  - BACKGROUND: The relationship between body mass index (BMI) and the severity of
      cardioembolic stroke (CES) remains poorly understood. METHOD: A total of 419
      consecutive CES patients with nonvalvular atrial fibrillation (NVAF), and with a
      modified Rankin Scale (mRS) score of 0 or 1 before onset admitted within 48hours
      after onset to the Hirosaki Stroke and Rehabilitation Center were studied. The
      patients were divided into three groups, low BMI (L-BMI; n = 36, BMI < 18.5
      kg/m2), normal BMI (N-BMI; n = 284, 18.5 <= BMI < 25.0), and high BMI (H-BMI; n =
      99, BMI >= 25.0). We compared stroke severity and functional outcome among the
      three groups. RESULTS: Stroke severity on admission, assessed by the National
      Institutes of Health Stroke Scale (NIHSS) showed that patients with L-BMI had the
      highest NIHSS score (median, 16 [11-25]), followed by N-BMI and H-BMI (11 [5-19]
      and 9 [3-19], P = .002). Functional outcome at discharge, assessed by mRS, was
      most severe in L-BMI patients (5 [3-5]), followed by N-BMI and H-BMI (3 [1-4] and
      2 [1-4], P = .001). Multivariate analyses revealed that L-BMI was a significant
      determinant of severe stroke (NIHSS scores >=8) at admission (odds ratio [OR] to
      N-BMI = 2.79, 95% confidence interval [CI], 1.17-7.78, P = .02) and poor
      functional outcome (mRS scores >=3) at discharge (OR = 2.53, 95% CI, 1.12-6.31, P
      = .02). However, H-BMI did not affect stroke severity at admission or functional
      outcome at discharge. CONCLUSION: Low BMI is a risk factor for severe stroke on
      admission and unfavorable functional outcome at discharge in Japanese CES
      patients with NVAF.

PMID- 30093202
TI  - Reimagining ARUBA: Theoretical Optimization of the Treatment of Unruptured Brain
      Arteriovenous Malformations.
AB  - BACKGROUND AND PURPOSE: The results of the A Randomized Trial of Unruptured Brain
      Arteriovenous (ARUBA) study, indicating that conservative medical management of
      unruptured brain arteriovenous malformations (UBAVM) is superior to
      interventional therapy, have generated debates that have hampered their
      application into clinical practice. Irrespectively of study conclusions, it seems
      reasonable to explore how much better interventional therapy would have to be to
      become competitive with conservative medical management. METHODS: We conducted an
      exploratory analysis to replicate the original data from ARUBA. The functional
      form of the replicated ARUBA data, according to their Weibull distribution,
      allowed estimation of parameters. We carried out Monte Carlo simulations while
      introducing theoretical reductions of interventional risk, and the results were
      used to construct theoretical and example Kaplan-Meier curves from simulations.
      RESULTS: The "ARUBA Replication" analysis showed results nearly identical to
      those published in the study, with an estimated hazard ratio of 0.27 (95% CI:
      0.14-0.55). At 50% interventional risk reduction, the simulations showed an
      estimated event rate of 14.9%, and the protective effect of conservative medical
      management was no longer statistically significant. Greater risk reductions
      hastened the time to benefit for interventional therapy, and an 80% risk
      reduction demonstrated superiority of interventional therapy at just over 2 years
      Hazard Ratio (HR: 1.44, 95% CI: 0.55-4.92). CONCLUSIONS: Reduction in risk of
      interventional therapy by 50%-80% results in more competitive clinical outcomes,
      equating or surpassing the benefit of conservative medical management of UBAVM.
      This conjecture should be taken into consideration in the design of future
      studies of this patient population, particularly because it is supported by
      recent observational studies.

PMID- 30093201
TI  - Biphasic Development of Focal Cerebral Hyperperfusion After Revascularization
      Surgery for Adult Moyamoya Disease Associated With Autosomal Dominant Polycystic
      Kidney Disease.
AB  - BACKGROUND: Cerebral hyperperfusion (CHP) syndrome is a potential complication of
      superficial temporal artery-middle cerebral artery (STA-MCA) anastomosis for
      moyamoya disease (MMD), but its biphasic and delayed development is extremely
      rare. CASE REPORT: A 47-year-old woman with autosomal dominant kidney disease
      (ADPKD) presented with transient ischemic attacks due to MMD, and underwent left
      STA-MCA anastomosis. N-isopropyl-p-[123I] iodoamphetamine single-photon emission
      computed tomography (123IMP-SPECT) 1 day after surgery revealed asymptomatic CHP
      at the site of anastomosis. Strict blood pressure control and minocycline
      hydrochloride relieved CHP at postoperative day 7. However, 2 days later, the
      patient complained of sensory aphasia, and 123IMP-SPECT demonstrated significant
      focal CHP at the site of anastomosis accompanying high-intensity signal on
      magnetic resonance (MR) imaging of fluid attenuated inversion recovery (FLAIR) in
      her left temporal lobe near the site of anastomosis. We continued strict blood
      pressure control and additionally administered free radical scavenger (Edaravone)
      and antiepileptic agents, which gradually improved sensory aphasia. MR imaging
      and 123IMP-SPECT also confirmed the amelioration of the FLAIR-high lesion and
      focal CHP in her left temporal lobe. Two months later, the patient underwent
      right STA-MCA anastomosis without complications. CONCLUSIONS: Although the
      underlying mechanism is unknown, biphasic development of focal CHP after
      revascularization surgery in an MMD patient with ADPKD is unique. Due to the
      potential vulnerability of the systemic vessels in ADPKD, it is conceivable that
      intrinsic vascular wall fragility in MMD could be enhanced by ADPKD and have
      partly led to this rare complication.

PMID- 30093203
TI  - Incidence and Predictors of the In-stent Restenosis after Vertebral Artery Ostium
      Stenting.
AB  - BACKGROUND: The incidence and predictors for in-stent restenosis (ISR) was not
      fully explored. We aim to investigate the incidence and predictors of ISR after
      stenting at the origin of vertebral artery. MATERIALS AND METHODS: Two hundred
      and six patients with 229 stents implantation between July 1, 2005 and July 31,
      2015 were included in the study. All patients underwent conventional clinical and
      angiographic (digital subtraction angiography) follow-up at around 6 months post
      procedure. ISR was defined as greater than 50% stenosis within or immediately
      (within 5 mm) adjacent to the stent. Multivariate Cox regression analyses were
      utilized to investigate the predictors for ISR. RESULTS: The ISR was found in 30
      patients (30/206, 14.6%) with 31 lesions (31/229, 13.5%) with the mean follow-up
      duration of 11.1-month (range: 3 - 92 months). Stent diameter (hazard ratio
      0.504, 95% confidence interval 0.294 - 0.864) was an independent predictor for
      ISR. CONCLUSION: ISR rate after Vertebral artery ostium stent placement is
      acceptable, which was conversely associated with the stent diameter.

PMID- 30093204
TI  - Efficacy of Cilostazol in Prevention of Delayed Cerebral Ischemia after
      Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis.
AB  - OBJECTIVES: Cilostazol, a selective inhibitor of phosphodiesterase 3, may reduce
      symptomatic vasospasm and improve outcome in patients with aneurysmal
      subarachnoid hemorrhage considering its anti-platelet and vasodilatory effects.
      We aimed to analyze the effects of cilostazol on symptomatic vasospasm and
      clinical outcome among patients with aneurysmal subarachnoid hemorrhage (aSAH).
      PATIENTS AND METHODS: We searched PubMed and Embase databases to identify 1)
      prospective randomized trials, and 2) retrospective trials, between May 2009 and
      May 2017, that investigated the effect of cilostazol in patients with aneurysmal
      aSAH. All patients were enrolled after repair of a ruptured aneurysm by clipping
      or endovascular coiling within 72hours of aSAH. fixed-effect models were used to
      pool data. We used the I2 statistic to measure heterogeneity between trials.
      RESULTS: Five studies were included in our meta-analysis, comprised of 543
      patients with aSAH (cilostazol [n=271]; placebo [n=272], mean age, 61.5years [SD,
      13.1]; women, 64.0%). Overall, cilostazol was associated with a decreased risk of
      symptomatic vasospasm (0.31, 95% CI 0.20 to 0.48; P<0.001), cerebral infarction
      (0.32, 95% CI 0.20 to 0.52; P <0.001) and poor outcome (0.40, 95% CI 0.25 to
      0.62; P<0.001). We observed no evidence for publication bias. Statistical
      heterogeneity was not present in any analysis. CONCLUSION: Cilostazol is
      associated with a decreased risk of symptomatic vasospasm and may be clinically
      useful in the treatment of delayed cerebral vasospasm in patients with aSAH. Our
      results highlight the need for a large multi-center trial to confirm the observed
      association.

PMID- 30093205
TI  - Spinal Cord Infarction: Clinical and Radiological Features.
AB  - INTRODUCTION: Spinal cord infarction is an uncommon disease varying in its
      clinical presentation. This study describes the clinical and radiological
      presentation of spinal cord infarcts in 17 consecutive patients. MATERIAL AND
      METHODS: Clinical and MR imaging data of 17 patients were reviewed. Inclusion
      criteria were acute or subacute presentation (peak within 72 hours) and MRI
      showing typical signal changes on T2WI compatible with spinal cord infarct.
      Exclusion criteria were clinical or MRI findings suggesting other etiologies.
      RESULTS: Clinical presentation included dissociative anesthesia, weakness of
      limbs, back or neck pain, and autonomic symptoms with symptom onset to peak time
      ranging from few minutes to 48 hours in patients with anterior spinal artery
      infarct (n = 16), and weakness and sensory loss in ipsilateral upper limb in
      patient with posterior spinal artery infarct (n = 1). One patient presented with
      "man-in-the-barrel syndrome (MIB)." MRI findings in anterior spinal artery
      infarcts included pencillike hyperintensities on T2 sagittal (n = 16, 100%) and
      "owl eye" appearance on T2 axial (n = 6, 37.5%) images. Diffusion restriction was
      noted in 8 cases and enhancement was noted in 2 cases. The posterior spinal
      artery infarct showed T2 hyperintensity in left posterior paramedian triangular
      distribution in cervical cord (C2-C7). Follow-up was available for 9 patients
      (period ranging from 15-41 months). Four patients had a favorable outcome who
      could walk independently, 1 patient could walk with support, and 2 patients were
      wheelchair bound. Two patients died. CONCLUSION: Spinal cord infarction is a rare
      but important cause of acute spinal syndrome. Typical distribution and
      appropriate imaging can help in timely diagnosis.

PMID- 30093206
TI  - RNF213 Genetic Variant and the Arterial Circle of Willis.

PMID- 30093207
TI  - Effectiveness and Safety of Antibiotics for Preventing Pneumonia and Improving
      Outcome after Acute Stroke: Systematic Review and Meta-analysis.
AB  - BACKGROUND: Pneumonia is a common complication after stroke which increases
      morbidity and mortality. This systematic review was conducted to evaluate the
      efficacy and safety of antibiotics for the prevention of pneumonia after acute
      stroke. METHODS: Medline, EMBASE, and Cochrane databases were searched for
      randomized controlled trials comparing preventive antibiotics to placebo or no
      antibiotics after acute stroke. The primary outcome was poststroke pneumonia.
      Secondary outcomes were all infections, urinary tract infections, death,
      dependency, length of hospital stay, and adverse events. Treatment effects were
      summarized using random effects metaanalysis. RESULTS: Six trials (4111 patients)
      were eligible for inclusion. The median National Institute of Health Stroke Scale
      score in included trials ranged from 5 to 16.5. The proportion of dysphagia
      ranged from 26% to 100%. Preventive antibiotics were commenced within 48hours
      after acute stroke. Compared to control, preventive antibiotics reduced the risk
      of poststroke pneumonia (RR .75, 95%CI ..57-.99), and all infections (RR .58,
      95%CI .48-.69). There was no significant difference in the risks of dependency
      (RR 0.99, 95%CI 0.80-1.11), or mortality (RR .96, 95%CI .78-1.19) between the
      preventive antibiotics and control groups. Preventive antibiotics did not
      increase the risk of elevated liver enzymes (RR 1.20, 95% CI .97-1.49).
      Preventive antibiotics had uncertain effects on the risks of other adverse
      events. CONCLUSION: Preventive antibiotics reduced the risk of post-stroke
      pneumonia. However, there is insufficient evidence to currently recommend routine
      use of preventive antibiotics after acute stroke.

PMID- 30093208
TI  - Response to Letter to the Editor Regarding "Genetic Analysis of Ring Finger
      Protein 213 (RNF213) c.14576G>A in Intracranial Atherosclerosis of the Anterior
      and Posterior Circulations".

PMID- 30093209
TI  - Fullerenol Nanoparticles Decrease Blood-Brain Barrier Interruption and Brain
      Edema during Cerebral Ischemia-Reperfusion Injury Probably by Reduction of
      Interleukin-6 and Matrix Metalloproteinase-9 Transcription.
AB  - BACKGROUND: The present study aimed to examine the protective role of fullerenol
      nanoparticles against blood-brain barrier (BBB) interruption and brain edema
      during cerebral ischemia-reperfusion injury probably by reduction of interleukin
      6 (IL-6) and matrix metalloproteinase-9 (MMP-9) transcription. METHODS: The male
      Wistar rats (weighting 280-320 g) were randomly assigned into four groups as
      follows: sham, control ischemic, pretreated ischemic, and posttreated ischemic
      groups. Cerebral ischemia-reperfusion (IR) injury was performed by occlusion of
      middle cerebral artery (MCA) for 90 minutes followed by twenty-four hours
      reperfusion. Rats were administered fullerenol 5mg/kg, intraperitoneally, 30
      minutes before induction of IR in pretreated ischemic group and immediately after
      termination of MCA occlusion in posttreated ischemic group. After twenty-four
      hours reperfusion, the method of Evans blue dye extravasation (EBE) and RT-PCR
      were used for determination of BBB permeability and mRNA expression levels of MMP
      9 and IL-6, respectively. Neuronal deficit score (NDS) and edema of the ischemic
      hemispheres were also evaluated. RESULTS: MCA occlusion increased NDS in control
      ischemic rats (3.16 +/- 0.16) with concomitant increase in EBE (15.30 +/-
      3.98ug/g) and edema (3.53 +/- 0.50%). Fullerenol in both pretreated and
      posttreated ischemic groups reduced NDS (36% and 68%, respectively), EBE (89% and
      91%, respectively) and edema (53% and 81%, respectively). Although MCA occlusion
      increased the mRNA expression levels of MMP-9 and IL-6 in ischemic hemispheres,
      fullerenol in both treatment groups noticeably decreased the mRNA expression
      levels of these genes. CONCLUSION: In conclusion, fullerenol nanoparticles can
      protect BBB integrity and attenuate brain edema after cerebral ischemia
      reperfusion injury possibly by reduction of IL-6 and MMP-9 transcription.

PMID- 30093210
TI  - Multimodal Rehabilitation Program Promotes Motor Function Recovery of Rats After
      Ischemic Stroke by Upregulating Expressions of GAP-43, SYN, HSP70, and C-MYC.
AB  - BACKGROUND: Despite the intense efforts devoted to preventing and treating
      cerebral ischemia, some individuals will continue to have completed infarctions.
      Failure of prevention or intervention does not, however, preclude therapeutic
      approaches to enhance recovery. Our study aims to explore the effect of
      multimodal rehabilitation program on the motor function recovery of rats with
      ischemic stroke. METHODS: Rat models of ischemic stroke were established using
      clean-grade adult male Sprague-Dawley rats. Motor function of rats was scored by
      the Bederson neurological function, balance beam test, and screen test. Nissl
      staining was conducted for morphological and structural changes of nerve cells in
      the arteriae cerebri anterior zone. Immunohistochemistry was applied to detect
      the expressions of growth-associated protein (GAP-43), synaptophysin (SYN) and
      Caspase-3, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling
      (TUNEL) staining was carried out in the corpus striatum 21 days after operation;
      reverse transcription quantitative polymerase chain reaction and Western blot
      analysis were conducted for testing messager RNA (mRNA) and protein expressions
      of heat shock protein 70 (Hsp70) and MYC proto-oncogene (c-Myc). RESULTS: Rats
      receiving multimodal rehabilitation program had lower Bederson neurological
      function, balance beam, and screen test scores on the 7th, 14th and 21st days
      after operation; more number of neurons surviving in the arteriae cerebri
      anterior zone at each time point after operation, higher GAP-43 expression on the
      7th and 14th days after operation, and higher SYN expression on the 14th and 21st
      days after operation, on the 7th, 14th and 21st days after operation, higher mRNA
      and protein expressions of HSP70 and C-MYC, lower Caspase-3 positive expression
      and TUNEL positive stained cells. CONCLUSIONS: Multimodal rehabilitation program
      could promote motor function recovery of rats after ischemic stroke by
      upregulating GAP-43 and SYN expressions at arteriae cerebri anterior zone and
      upregulating HSP70 and C-MYC expressions in the brain tissues.

PMID- 30093211
TI  - Prostate cancer treatment by the latest focal HIFU device with MRI/TRUS-fusion
      control biopsies: A prospective evaluation.
AB  - OBJECTIVES: Magnetic resonance imaging/transrectal ultrasound (MRI/TRUS) fusion
      guided focal high intensity focused ultrasound (HIFU) therapy of the prostate has
      recently been developed as a selective HIFU-therapy technique to enable targeted
      ablation of prostate cancer. Here we report a series of patients treated with
      focal HIFU therapy, discuss its potential pitfalls, and address controversies
      concerning the indications. MATERIALS AND METHODS: This single-center prospective
      study reports outcomes of patients treated from September 2014 to March 2016.
      Follow-up was a minimum of 12 months. MRI/TRUS-fusion-guided HIFU was performed
      under general anesthesia using the Focal One(r) device (EDAP, France). A control
      biopsy at 12 months was taken using the MRI/TRUS-fusion biopsy platform ArtemisTM
      (Eigen, California) combining targeted and systematic cores. Prostate-specific
      antigen (PSA) changes from baseline, patient-reported outcome measures, and
      complications using the Clavien-Dindo classification system are also reported.
      RESULTS: Twenty-four patients (PSA < 10 ng/ml, n = 17 Gleason 3+3, n = 7 Gleason
      3+4) with either unifocal or bifocal prostate imaging reporting and data system
      (PI-RADS) 3-5 lesions (n = 19) or without a PI-RADS lesion (n = 5) were treated.
      Nineteen patients underwent focal HIFU, five patients zonal HIFU. Of the 20
      patients that had biopsies at 12 months, 8 patients had a positive biopsy within
      the ablation zone (overall cancer free rate: 60%). Using different definitions of
      clinically significant cancer, the cancer-free rate for the ablation zone varies
      between 75% and 95%. Four of the eight patients (all persistent Gleason 3+4 or
      upgrading to 4+3) underwent a radical whole gland salvage therapy. Patient
      reported outcome measures showed no significant decrease in urinary continence
      (expanded prostate cancer index composite -26 urinary incontinence: P = 0.080),
      but there was a reduction in potency (International index of erectile function in
      preoperatively potent patients: median decrease of 2 points to a median of 19
      points at 12 months; 95% confidence interval: 15.79-22.21; P = 0.044). Only one
      complication > grade II occurred. CONCLUSIONS: Targeted MRI/TRUS fusion-guided
      focal HIFU allows local tumor ablation, but is not free from limitations. The
      procedure has good functional outcomes and a quick recovery. Multicenter trials
      with more patients are required to determine the procedure's role in the prostate
      cancer therapy algorithm.

PMID- 30093213
TI  - Corrigendum to "Chemical characterization and cerebroprotective effect of
      methanolic root extract of Colebrookea oppositifolia in rats" [J. Ethnopharmacol.
      223 15 (2018) 63-75].

PMID- 30093212
TI  - Genetics of micronodular adrenal hyperplasia and Carney complex.
AB  - Micronodular bilateral adrenal hyperplasia (MiBAH) is a rare cause of adrenal
      Cushing syndrome (CS). The investigations carried out on this disorder during the
      last two decades suggested that it could be divided into at least two entities:
      primary pigmented nodular adrenocortical disease (PPNAD) and isolated
      micronodular adrenocortical disease (i-MAD). The most common presentation of
      MiBAH is familial PPNAD as part of Carney complex (CNC) (cPPNAD). CNC, associated
      with multiple endocrine and non-endocrine neoplasias, was first described in 1985
      in 40 patients, 10 of whom were familial cases. In 2000, we identified
      inactivating germline mutations of the PRKAR1A gene, encoding the regulatory
      subunit type 1alpha (RIalpha) of protein kinase A (PKA), in the majority of
      patients with CNC and PPNAD. PRKAR1A mutations causing CNC lead to increased PKA
      activity. Since then, additional genetic alterations in the cAMP/PKA signaling
      pathway leading to increased PKA activity have been described in association with
      MiBAH. This review summarizes older and recent findings on the genetics and
      pathophysiology of MiBAH, PPNAD, and related disorders.

PMID- 30093214
TI  - Dynamic Contrast-Enhanced Magnetic Resonance Lymphangiography and Percutaneous
      Lymphatic Embolization for the Diagnosis and Treatment of Recurrent Chyloptysis.
AB  - Chyloptysis, or the expectoration of triglyceride-rich sputum, is rare and
      typically treated with diet modification and thoracic duct ligation. This article
      describes 2 patients with prolonged histories of chyloptysis who failed
      conservative treatment and thoracic duct ligation. Dynamic contrast-enhanced
      magnetic resonance imaging delineated the lymphatic anatomy and identified the
      abnormal pulmonary lymphatic perfusion pathways in both patients. This imaging
      provided guidance for successful percutaneous lymphatic embolization which
      resulted in resolution of symptoms in both patients.

PMID- 30093215
TI  - Downstream Costs Associated with Incidental Pulmonary Nodules Detected on CT.
AB  - RATIONALE AND OBJECTIVES: To explore downstream costs associated with incidental
      pulmonary nodules detected on CT. MATERIALS AND METHODS: The cohort comprised 200
      patients with an incidental pulmonary nodule on chest CT. Downstream events
      (chest CT, PET/CT, office visits, percutaneous biopsy, and wedge resection) were
      identified from the electronic medical record. The 2017 Fleischner Society
      Guidelines were used to classify radiologists' recommendations and ordering
      physician management for the nodules. Downstream costs for nodule management were
      estimated from national Medicare rates, and average costs were determined.
      RESULTS: Average downstream cost per nodule was $393. Costs were greater when
      ordering physicians over-managed relative to radiologist recommendations ($940)
      vs. when adherent ($637) or under-managing ($166) relative to radiologists
      recommendations. Costs were also greater when ordering physicians over-managed
      relative to Fleischner Society guidelines ($860) vs. when under-managing ($208)
      or adherent ($292) to guidelines. Costs did not vary significantly based on
      whether or not radiologists recommended follow-up imaging ($167-$397), nor
      whether radiologists were adherent or under- or over-recommended relative to
      Fleischner Society guidelines ($313-$444). Costs were also higher in older
      patients, patients with a smoking history, and larger nodules. Five nodules
      underwent wedge resection and diagnosed as malignancies. No patient demonstrated
      recurrence or metastasis. Average cost per diagnosed malignancy was $3090.
      CONCLUSION: Downstream costs for incidental pulmonary nodules are highly variable
      and particularly high when ordering physicians over-manage relative to
      radiologist recommendations and Fleischner Society guidelines. To reduce
      unnecessary utilization and cost from over-management, radiologists may need to
      assume a greater role in partnering with ordering physicians to ensure
      appropriate, guideline-adherent, and follow-up testing.

PMID- 30093217
TI  - Current Advances in COPD Imaging.
AB  - OBJECTIVE: To review the recent advances in available technologies for imaging
      COPD and present the novel optical coherence tomography (OCT) airway imaging
      technology. MATERIALS AND METHODS: This is an unstructured review of published
      evidence of available pulmonary imaging technologies along with a demonstration
      of state-of-the-art OCT imaging technology of in vivo human and animal airways.
      RESULTS: Advanced imaging techniques such as Magnetic Resonance (MR) imaging
      using hyperoloarized noble gases, micro-Computed Tomography (micro-CT), and OCT
      aim to further our understanding of COPD. Lung densitometry can aid in
      identifying an exacerbation prone phenotype which may have implications for
      targeting specific therapies to these individuals. MR ventilation scans have the
      ability to provide a functional and regional distribution of airflow obstruction
      offering insight into the airway and parenchymal changes induced by COPD. Micro
      CT gives a near microscopic view of the terminal bronchioles and alveoli
      permitting study of the microarchitecture of the lung ex vivo. Optical coherence
      tomography can visualize the microstructure of the airway walls (epithelium,
      smooth muscle, blood vessels, cartilage) permitting real time in vivo as well as
      longitudinal evaluation of airway changes in patients with COPD. CONCLUSION:
      Advanced imaging techniques play a vital role in expanding our current
      understanding of COPD.

PMID- 30093216
TI  - Low-Dose Coronary CT Angiography in Patients with Atrial Fibrillation: Comparison
      of Image Quality and Radiation Exposure with Two Different Approaches.
AB  - RATIONALE AND OBJECTIVES: To evaluate image quality, coronary interpretability
      and radiation exposure of coronary CT angiography (CCTA) performed in patients
      with atrial fibrillation (AF) with the latest scanner generation, comparing two
      different technical approaches. A new scanner that combines a 0.23 mm spatial
      resolution, a new generation of iterative reconstruction, fast gantry rotation
      time and the intracycle motion-correction algorithm to improve the temporal
      resolution was recently introduced in the clinical field. MATERIALS AND METHODS:
      We enrolled 105 consecutive patients with chronic AF who performed CCTA with a
      whole-heart coverage high-definition CT scanner (16-cm z-axis coverage with 256
      detector rows, 0.28 s gantry rotation time). Five of them were excluded for
      impaired renal function. Patients were randomized between a double acquisition
      protocol (50 patients, group 1) or a single acquisition protocol (50 patients,
      group 2). The image quality, coronary segment interpretability and effective dose
      (ED) of CCTA were assessed. RESULTS: The mean HR during the scan was 85.6+/-21
      bpm in group 1 vs. 83.7+/-23 bpm in Group 2, respectively (p < ns). In group 2,
      overall image quality was high and comparable with that of group 1 (Likert scale
      =3.2 +/- 1.4 vs. 3.3 +/- 1.2, p = ns, in group 1 and 2, respectively). Coronary
      interpretability was high and similar between the two groups (97.5% and 97.1% in
      group 1 and 2, p = ns, respectively). Mean ED was significantly higher in group 1
      than in group 2 (5.3 +/- 1.8 mSv vs. 2.7 +/- 0.7 mSv, p < 0.001). CONCLUSION: The
      novel whole-heart coverage CT scanner allows to perform CCTA with a single
      acquisition protocol with high image quality and low radiation exposure in AF
      patients.

PMID- 30093219
TI  - Arthrodesis for Treatment of Intra-Articular Synovial Cysts of the Hallux
      Interphalangeal Joint.
AB  - Synovial cysts are benign tissue masses that develop near joints and tendons as a
      result of fluid leakage. They can be difficult to eradicate, and adjacent tendon
      and joint surfaces can complicate their treatment. We retrospectively analyzed
      the data from 4 consecutive patients who had undergone hallux interphalangeal
      fusion from January 2009 to December 2010. Of the 4 patients, 3 were male and 1
      was female, with a mean age of 55 +/- 22 (range 26 to 79) years. These 4 patients
      had developed painful interphalangeal arthritis with radiographic cystic changes
      of 1 to 4 years' duration. All patients were treated at a single facility, with
      surgical fixation of the joint performed by insertion of a single 4.3-mm headless
      lag screw across the interphalangeal joint. A final postoperative follow-up
      examination was performed at 22 +/- 7 (range 14 to 30) months postoperatively.
      The mean American Orthopaedic Foot and Ankle Society hallux functional scores
      increased significantly from 70.8 +/- 6.1 preoperatively to 90.5 +/- 5.2
      postoperatively (p < .01). No complications were observed, and complete
      interphalangeal joint fusion was observed at a mean of 9.2 +/- 1.2 weeks. In
      conclusion, these preliminary data suggest that arthrodesis is an alternative
      effective treatment of symptomatic synovial cyst formation localized to the
      hallux interphalangeal joint.

PMID- 30093224
TI  - Forging the Road Ahead in Immunology.

PMID- 30093218
TI  - Microvascular Endothelial Function and Neurocognition Among Adults With Major
      Depressive Disorder.
AB  - BACKGROUND: Cardiovascular risk factors (CVRFs) and endothelial dysfunction have
      been associated independently with poorer neurocognition in middle-aged adults,
      particularly on tests of frontal lobe function. However, to our knowledge, no
      studies have examined markers of microvascular dysfunction on neurocognition or
      the potential interaction between macro- and microvascular biomarkers on
      neurocognition in middle-aged and older adults with major depressive disorder
      (MDD). METHODS: Participants included 202 adults with MDD who were not receiving
      mental health treatment. Microvascular endothelial function was assessed using a
      noninvasive marker of forearm reactive hyperemia velocity while macrovascular
      endothelial function was assessed using flow-mediated dilation (FMD) of the
      brachial artery. CVRFs were assessed using the Framingham Stroke Risk Profile and
      fasting lipid levels. A standardized neurocognitive assessment battery was used
      to assess three cognitive domains: executive function, working memory, and verbal
      memory. RESULTS: Greater microvascular dysfunction was associated with poorer
      neurocognition across all three domains. Microvascular function continued to
      predict verbal memory performance after accounting for background factors and
      CVRFs. Macro- and microvascular function interacted to predict working memory
      performance (F = 4.511, 178, p = 0.035), with a similar nonsignificant
      association for executive function (F = 2.731, 178, p = 0.095), with moderate
      associations observed between microvascular function and neurocognition in the
      presence of preserved FMD (r61 = 0.40, p = 0.001), but not when FMD was impaired
      (r63 = -0.05, p = 0.675). CONCLUSION: Greater microvascular dysfunction is
      associated with poorer neurocognition among middle-aged and older adults. This
      association was strongest in participants with preserved macrovascular function.

PMID- 30093225
TI  - Glucose tolerant and glucose stimulated beta-glucosidases - A review.
AB  - The beta-glucosidases (beta-D-glucoside glucohydrolase, EC 3.2.1.21) hydrolyze
      glycosidic bonds of alkyl-, amino-, or aryl-beta-D-glucosides, cyanogenic
      glucosides, disaccharides and short oligosaccharides and can also catalyze the
      synthesis of glycosyl-bonds between different molecules via transglycosylation.
      Due to their ubiquitous phylogenetic distribution, substrate diversity and
      ability to both hydrolyze and synthesize glycosidic bonds, the catalysis and
      regulation of beta-glucosidases have been extensively studied. Many beta
      glucosidases are inhibited by the reaction product glucose, and reduced catalytic
      activity may limit the biotechnological and industrial applications of these
      enzymes and this has stimulated the search for beta-glucosidases that maintain
      their activity at high glucose concentrations. Studies of many glucose tolerant
      enzymes have been reported and due to the ongoing interest in these enzymes, here
      it has been reviewed this accumulated body of knowledge which provides valuable
      insights as to the kinetics, structure, regulation and evolution of glucose
      tolerant and glucose stimulated beta-glucosidases.

PMID- 30093226
TI  - Quercetin potentiates the concurrent hyper-accumulation of cellular biomass and
      lipids in Chlorella vulgaris.
AB  - Provision of chemical modulators has emerged as an effective strategy to govern
      cell growth and development. Here, the impact of flavonoid quercetin on algal
      growth, lipid accumulation and transcriptional patterns was investigated in the
      green microalga Chlorella vulgaris. These results demonstrated that quercetin (15
      MUg/l) significantly enhanced the cellular biomass and photosynthetic efficiency,
      with up to 2.5-fold in the biomass in the stationary phase. Lipidomic analyses
      revealed that lipid content was increased by 1.8-fold. Furthermore, the
      functional mechanism of quercetin on the molecular level was dissected by
      transcriptomic analysis. Results revealed that quercetin upregulated the
      expression pattern of key genes involved in cellular signaling mechanisms such as
      phosphatidylinositol 4-kinase alpha, thus consequently enhanced cell growth.
      Altogether, the data present in this study demonstrate the dramatic role of
      quercetin on enhancing microalgal biomass and lipid accumulation by unprecedented
      regulation, of key metabolic nodes, for the first time and provide a novel
      insight into microalgal metabolism and regulation.

PMID- 30093228
TI  - Ethnic and racial disparities and differences in sudden cardiac death burden and
      survival: How do we close the gap?

PMID- 30093227
TI  - Safety and activity findings from a phase 1b escalation study of mirvetuximab
      soravtansine, a folate receptor alpha (FRalpha)-targeting antibody-drug conjugate
      (ADC), in combination with carboplatin in patients with platinum-sensitive
      ovarian cancer.
AB  - PURPOSE: To evaluate the safety profile and preliminary antitumor activity of
      mirvetuximab soravtansine when administered in combination with carboplatin to
      relapsed ovarian cancer patients. METHODS: Patients with recurrent, platinum
      sensitive epithelial ovarian or fallopian tube cancer were enrolled. Eligibility
      included a minimum requirement of tumor FRalpha positivity (>=25% of cells with
      >=2+ staining intensity). Patients received escalating doses of mirvetuximab
      soravtansine and carboplatin on day 1 of a 21-day cycle (once every 3 weeks).
      Mirvetuximab soravtansine maintenance therapy was permitted, at the investigators
      discretion, following cessation of carboplatin treatment. Adverse events, tumor
      response, and progression-free survival (PFS) were determined. RESULTS: Eighteen
      patients were enrolled and dosed with combination therapy; thirteen continued
      with mirvetuximab soravtansine maintenance following carboplatin discontinuation.
      Mirvetuximab soravtansine dosing was escalated from 5 to 6 mg/kg (adjusted ideal
      body weight) and carboplatin from AUC4 to AUC5. Adverse events were generally
      mild (<= grade 2) with nausea, diarrhea, thrombocytopenia, blurred vision, and
      fatigue being the most common treatment-emergent toxicities. For all evaluable
      patients (n = 17), the confirmed objective response rate (ORR) was 71%, including
      three complete responses and nine partial responses, and the median PFS was 15
      months. A median duration of response was not reached. CONCLUSION: These data
      demonstrate that mirvetuximab soravtansine combined with carboplatin is a well
      tolerated and highly active regimen in recurrent, platinum-sensitive ovarian
      cancer. Further evaluation of this combination in a randomized fashion is
      warranted.

PMID- 30093229
TI  - Non-technical skills training in the operating theatre: A meta-analysis of
      patient outcomes.
AB  - BACKGROUND: Non-technical skills (NTS) failures have been implicated in a large
      proportion of surgical errors. The objective of this meta-analysis was to
      investigate whether NTS training of theatre staff improves patient outcomes.
      METHODS: In a systematic literature search all interventional studies evaluating
      the effects of NTS training of theatre staff were identified. Primary outcomes
      included mortality, morbidity, readmission rate and length of hospital stay.
      Secondary outcomes included staff NTS, checklist use and technical surgical
      performance. Pooled odds ratios (OR) were determined for event rates and weighted
      mean differences (WMD) for continuous data. An inverse variance method in a
      random effects model was used for meta-analysis. RESULTS: A total of 1381 records
      were identified and nine studies were included. Meta-analysis of mortality was
      not carried out because only two controlled studies with different study designs
      were identified. No statistically significant differences were seen in
      complication rate (5 studies, OR 0.91 [0.73, 1.14]; p = 0.43), readmission rate
      (3 studies, OR 0.90 [0.63, 1.28], p = 0.56) and length of hospital stay (3
      studies, WMD -0.88 days [-2.06, 0.31], p = 0.31) after NTS training. Of the
      secondary outcomes, an improvement of whole team NOTECHS II scores was observed
      in the intervention group (3 studies, WMD 6.97 [3.88, 10.06], p < 0.0001).
      Technical performance and checklist use were unchanged. CONCLUSIONS: This meta
      analysis failed to find a statistically significant improvement of patient
      outcomes. These conclusions are based on a small number of heterogeneous studies.
      Further appropriately powered studies are likely to improve our understanding of
      the effects of NTS training.

PMID- 30093230
TI  - Letter to the Editor regarding Gyftopoulos et al: "Cost-effectiveness of magnetic
      resonance imaging versus ultrasound for the detection of symptomatic full
      thickness supraspinatus tendon tears".

PMID- 30093231
TI  - Response to Nazarian et al regarding: "Cost-effectiveness of magnetic resonance
      imaging versus ultrasound for the detection of symptomatic full-thickness
      supraspinatus tendon tears".

PMID- 30093232
TI  - Clinical and radiologic outcomes following total shoulder arthroplasty using
      Arthrex Eclipse stemless humeral component with minimum 2 years' follow-up.
AB  - BACKGROUND: Stemless humeral components benefit from less morbidity, better
      reproduction of the humeral anatomy, ease of revision, and fewer stem-related
      complications. Encouraging results are available up to 9 years after surgery from
      the designer's series. This is an independent study of 100 consecutive Eclipse
      stemless prostheses for osteoarthritis with a minimum 2-year follow-up (range, 2
      6 years). METHODS: We included only total shoulder arthroplasties performed for
      osteoarthritis. The primary outcome was the Oxford Shoulder Score (OSS) after 2
      years. Secondary outcome measures were change in shoulder range of movement and
      radiographic analysis of prosthesis size and position. RESULTS: The mean OSS at 2
      years was 38 of 48, with a mean improvement of +19 points (range, +17 to +22
      points; P < .001). There was no significant deterioration in OSS after 3 or 4
      years' follow-up. Statistically significant improvement was seen in arm elevation
      and external rotation (P < .001). There were 5 reoperations-1 for impingement of
      the biceps stump and 4 revisions to reverse arthroplasty for cuff failure. Of the
      prostheses, 92% were sized within 2 mm of the anatomic head size, and in 76% of
      prostheses, the center of rotation was within 3 mm of the native anatomy. An
      incomplete radiolucent line was present in zone B (around the cage screw) in a
      single patient at 2 years following surgery. There were no cases of loosening or
      infection. CONCLUSION: The functional and radiographic outcomes of Eclipse total
      shoulder replacement are excellent. We were able to accurately reproduce the
      native anatomy in the majority of cases, with no implant loosening, at 2 to 6
      years' follow-up.

PMID- 30093233
TI  - Distal triceps transosseous cruciate versus suture anchor repair using equal
      constructs: a biomechanical comparison.
AB  - BACKGROUND/HYPOTHESIS: Suture anchor-based repair has been advocated for repair
      of distal triceps avulsion, but previous models have used an unequal number of
      sutures across the repair site. We hypothesized that there would be no difference
      in triceps tendon displacement between gold standard repair with transosseous
      cruciate bone tunnels and suture anchor repair with an equal number of sutures in
      the constructs. METHODS: The triceps tendon footprint was measured in 20
      cadaveric elbows (10 matched pairs), and a distal triceps tendon rupture was
      created. The specimens in each pair were randomly assigned to transosseous
      cruciate repair or knotless, double-row, anatomic footprint, suture anchor
      repair. Specimens underwent cyclic loading to 1500 cycles and then load to
      failure. Footprint uncoverage was measured at 1500 cycles. Data for medial and
      lateral triceps tendon displacement, footprint uncoverage, and failure load were
      obtained. RESULTS: Triceps displacement did not differ significantly between the
      transosseous cruciate and the suture anchor repair group at 1500 cycles on the
      medial (3.6 +/-  0.9 mm vs. 4.3 +/- 1.6 mm [mean +/- standard deviation],
      respectively; P = .27) and lateral side (3.1 +/- 1.2 mm vs. 2.0 +/- 1.2 mm,
      respectively; P = .06). No other differences were found between the constructs.
      DISCUSSION/CONCLUSION: Transosseous cruciate distal triceps repair and knotless
      double-row suture anchor repair using constructs with an equal number of sutures
      showed no significant difference in tendon displacement at 1500 loading cycles.
      These findings suggest that the biomechanical strength of an all-suture construct
      is not different from that of suture anchors for repair of distal triceps
      avulsions.

PMID- 30093234
TI  - Incidence and risk factors for aseptic baseplate loosening of reverse total
      shoulder arthroplasty.
AB  - BACKGROUND: Aseptic glenoid baseplate loosening (AGBL) is a catastrophic
      complication after reverse total shoulder arthroplasty (RTSA). Our goals were to
      determine the incidence of AGBL in patients who underwent RTSA and identify risk
      factors for AGBL after RTSA. METHODS: We analyzed 202 shoulders that underwent
      primary or revision RTSA using 1 implant system and evaluated baseplate loosening
      at a minimum 2-year follow-up. The associations between AGBL and the following
      variables were investigated: patient age, sex, primary vs. revision RTSA,
      scapular notching, use of bone graft, and type of baseplate screw fixation.
      RESULTS: AGBL occurred in 6 shoulders (3.0%). The incidence of AGBL after
      revision RTSA (10%) was significantly higher than that after primary RTSA (1.2%;
      P = .014). There were significant associations between AGBL and the use of bone
      graft and the use of nonlocking screws. Scapular notching, glenosphere center-of
      rotation offset, patient age, and sex were not associated with AGBL. Multiple
      logistic regression analysis showed that the use of all peripheral nonlocking 3.5
      mm screws (odds ratio, 10.6; 95% confidence interval, 1.1- 39) and the use of
      bone graft (odds ratio, 7.5; 95% confidence interval, 1.9-30) were independent
      risk factors for AGBL. CONCLUSIONS: The rate of baseplate failure after primary
      RTSA is low (1.2%) but is significantly higher after revision RTSA (10%). Major
      risk factors for baseplate failure are the use of all 3.5-mm nonlocking screws
      for peripheral baseplate fixation and the use of a bone graft to address
      deficiencies in bony support beneath the baseplate.

PMID- 30093235
TI  - Epibionts on Turbinaria ornata, a secondary foundational macroalga on coral
      reefs, provide diverse trophic support to fishes.
AB  - Worldwide, many coral reef ecosystems have shifted from coral to algal dominance,
      yet the ecological function of these emergent communities remains relatively
      unknown. Turbinaria ornata, a macroalga with a rapidly expanding range in the
      South Pacific, forms dense stands on hard substrate, likely providing ecological
      services unique from corals. While generally unpalatable, T. ornata can function
      as a secondary foundation species and hosts an epibiont community that may
      provide overlooked trophic resources in phase shifted reef ecosystems. Results
      from video recorded field experiments designed to quantify consumer pressure on
      T. ornata epibionts showed that both consumer pressure and epibiont cover
      increased with thallus size. Additionally, most fish species, including
      herbivores, omnivores, and detritivores, exhibited higher bite rates on thalli
      with epibionts compared to thali with epibionts experimentally removed. Juvenile
      parrotfishes were responsible for 50% of total bites recorded and also had the
      highest bite rates. Results indicate that epibionts, particularly on large T.
      ornata, are a food resource for a diversity of fishes, representing a previously
      undescribed function of this macroalga in coral reef ecosystems. Exploring the
      functions of macroalgal dominated reef communities will be increasingly important
      as reefs continue to phase shift toward macroalgal dominance in the Anthropocene.

PMID- 30093236
TI  - Impoverished mobile epifaunal assemblages associated with the invasive macroalga
      Asparagopsis taxiformis in the Mediterranean Sea.
AB  - There is an increasing concern about the ecosystem consequences of altering
      macroalgal assemblages. Many macrophytes are foundation species in coastal
      habitats, supporting much of the biodiversity of these ecosystems by providing
      essential resources such as food and habitat. The addition of invasive species
      strongly contributes to habitat modification, but the bottom-up impacts of non
      native macroalgae on higher trophic levels remains difficult to predict. The main
      aim of this study was to evaluate the effects of the invasive macroalga
      Asparagopsis taxiformis on biodiversity by comparing the mobile macrofauna
      inhabiting this species to the dominant native species Halopteris scoparia. This
      is the first comprehensive study of the possible effects of this widespread
      invasive species on higher trophic levels. A hierarchical sampling design with
      two different spatial scales was conducted to explore the consistency of the
      patterns observed. Fifty-nine species belonging to superorder Peracarida were
      found, accounting 90% of all organisms. A. taxiformis hosted an impoverished
      epifaunal assemblage in comparison to that associated with the native seaweed,
      showing significantly lower values of diversity, abundance and number of
      epifaunal species across study locations. The structure of the associated
      macrofauna (both in terms of species composition, variability among samples and
      relative abundance of the species) was also different. Our results highlighted
      the strong influence of A. taxiformis in the resident community, with differences
      among the two macroalgae in all the parameters considered. Finally, our results
      also reflect a biotic homogenization of the epifaunal assemblages associated to
      A. taxiformis, a scarcely explored consequence of invasive processes in marine
      environments. Future studies exploring the cascading effects of the observed
      changes in the epifaunal assemblages would be necessary in order to estimate
      system responses to macroalgal invasions.

PMID- 30093237
TI  - Foot and ankle characteristics in systemic lupus erythematosus: A systematic
      review and meta-analysis.
AB  - OBJECTIVE: To determine characteristics of the foot and ankle in people with
      systemic lupus erythematosus (SLE). METHODS: Medline, CINAHL, Sports-Discus,
      Scopus and Cochrane Library databases were searched up to January 2018. Studies
      reporting foot- and ankle-related outcomes in the following domains were
      included: vascular, neurological, musculoskeletal, cutaneous (skin and nail) or
      pain/function. The Quality Index tool was used to assess methodological quality.
      Where appropriate, odds ratio (OR) and mean difference meta-analyses were
      conducted for case-control studies; and pooled mean prevalence meta-analyses for
      studies assessing characteristics in SLE. RESULTS: Forty-nine studies were
      included with mean (range) quality scores of 75% (38-100%). Twenty-three studies
      assessed vascular characteristics, followed by musculoskeletal (n = 16),
      neurological (n = 11), cutaneous (n = 5) and pain/function (n = 4). Foot and
      ankle characteristics in people with SLE included impaired vascular supply,
      abnormal nerve function, musculoskeletal pathology, skin and nail pathology, and
      pain and functional disability. Twenty-four studies were included in meta
      analyses. Pooled OR for abnormal ankle brachial index was 3.08 for SLE compared
      with controls. Pooled mean difference in brachial-ankle pulse-wave velocity
      between SLE and controls was significant (161.39 cm/s, P = 0.004). Pooled
      prevalence was 0.54 for intermittent claudication, 0.50 for Raynaud's phenomenon,
      0.28 for chilblains, 0.00 for gangrene, 0.30 for hallux valgus, 0.15 for
      onychomycosis, 0.76 for history of foot pain, and 0.36 for current foot pain.
      CONCLUSION: People with SLE experience a wide range of foot and ankle
      manifestations. Published research highlights the impact of peripheral arterial
      disease, peripheral neuropathy, musculoskeletal deformity, skin and nail
      pathology and patient-reported foot pain and disability.

PMID- 30093238
TI  - Acceptance rate and sociological factors involved in the switch from originator
      to biosimilar etanercept (SB4).
AB  - OBJECTIVE: To study acceptance rate and factors influencing acceptance of the
      switch from originator etanercept (Enbrel(c)) to biosimilar etanercept (SB4,
      Benepali(c)) in patients with rheumatic disease. METHODS: Patients with a well
      controlled rheumatic disease consulting in our rheumatology department were
      offered the switch for SB4. After oral and written information concerning
      biosimilar, free choice to accept the switch was left to the patients. The main
      outcome was primary switch acceptance rate defined by switch acceptance during
      the initial consult. Real switch adherence, socio-cultural factors and beliefs
      influencing switch acceptance rate were retrieved during a telephonic interview
      at distance from the consultation. RESULTS: Fifty-two patients were eligible for
      the switch: 32 (62%) with spondyloarthritis and 20 (38%) with rheumatoid
      arthritis. The primary acceptance rate was 92% (48/52). Patients refusing the
      switch were more likely to report a bad opinion on generic drugs (100% vs 11%, p
      < 0.001). Other patient characteristics were roughly identical except for a
      statistical trend in the refusal group toward older age (61.4 vs 50.7 years, p =
      0.08) and longer disease duration (26 vs 12.1 years, p = 0.05). Despite initial
      acceptance, two patients did not begin SB4 after receiving negative information
      by their regular pharmacist. Real SB4 switch rate was 85% (44/52) and 86% (38/44)
      of patients reported a good experience of the switch. CONCLUSIONS: Acceptance
      rate of the switch from originator to biosimilar etanercept is high. Patient
      information, physician and pharmacist knowledge on biosimilars should be taken
      into account in order to improve their diffusion.

PMID- 30093239
TI  - Smoking as a risk factor for giant cell arteritis: A systematic review and meta
      analysis.
AB  - OBJECTIVES: To investigate the association between smoking and giant cell
      arteritis (GCA). METHODS: A systematic review was performed and meta-analysis
      conducted on observational studies that reported absolute numbers and/or
      statistical comparisons with 95% confidence intervals comparing smoking history
      and presence of GCA, among patients with GCA and non-GCA controls. Studies were
      reviewed in accordance with PRISMA guidelines. Point estimates and standard
      errors were extracted from individual studies and were combined by the generic
      inverse variance method of DerSimonian and Laird. A random-effects meta-analysis
      was performed. Statistical heterogeneity was assessed using the Cochran's Q test
      which was complemented with the I2 statistic. RESULTS: The initial search yielded
      3312 articles. Of these, thirteen studies (8 prospective and, 5 retrospective
      case-control studies) with unique cohorts were identified and included in the
      primary analysis (ever vs. never smoking history). Patients in the GCA cohort
      were more likely to have a history of smoking with an odds ratio of 1.19 (95% CI,
      1.01-1.39). Considerable heterogeneity was present (I2 = 85%). Five of these
      studies included information on current smoking status. One additional study,
      which only reported current smoking status, was also included. The GCA cohort
      showed an association with current smoking with an odds ratio of 1.18 (95% CI,
      1.01-1.38). CONCLUSION: Our study demonstrated a statistically significant
      increased risk of GCA among both current and ever smokers compared to non
      smokers.

PMID- 30093240
TI  - High serum levels of silica nanoparticles in systemic sclerosis patients with
      occupational exposure: Possible pathogenetic role in disease phenotypes.
AB  - BACKGROUND: Systemic sclerosis (SSc) is an autoimmune systemic disease
      characterized by diffuse fibrosis of skin and visceral organs due to different
      genetic, infectious, and/or environmental/occupational causative factors,
      including the inhalation of silica dust. OBJECTIVES: To investigate serum trace
      elements including silicon (s-Si) levels in SSc patients living in a restricted
      geographical area with high density of worksites with silica exposure hazard.
      METHODS: This case-control study included 80 SSc patients (M:F 10:70; aged 58.4
      +/- 11.9SD years, mean disease duration 10.1 +/- 7.8SD) and 50 age-/sex-matched
      healthy control subjects consecutively investigated at our University-based
      Rheumatology Unit. Patients and controls were evaluated for
      environmental/occupational exposure categories (structured questionnaire),
      morphological characterization of serum micro-/nanoparticles (Environmental
      Scanning Electron Microscopy and Energy Dispersive X-ray Spectroscopy
      microanalysis), and quantitative assessment of trace elements (inductively
      coupled plasma atomic emission spectroscopy). RESULTS: Among various categories,
      only occupational exposure to silica dust was recorded in a significant
      proportion of SSc patients compared to controls (55% vs. 11%; p < .0001).
      Qualitative analysis showed serum silica micro- and nanoparticles in all exposed
      patients. Quantitative evaluation evidenced significantly higher s-Si levels in
      SSc patients versus controls (p < .0001); in addition, higher s-Si levels were
      detected in patients with occupational exposure (p < .0001), diffuse cutaneous
      SSc (p = .0047), myositis (p = .0304), and/or lung fibrosis (p = .0004) compared
      to those without; notably, the severity of lung fibrosis scoring positively
      correlated with s-Si levels (p < .0001). CONCLUSIONS: The study first
      demonstrated high s-Si levels in exposed SSc patients; this element might
      represent a pathogenetic co-factor of more severe clinical phenotypes, mainly
      diffuse scleroderma with lung fibrosis.

PMID- 30093241
TI  - A New Measure of Health Numeracy: Brief Medical Numbers Test (BMNT).
AB  - BACKGROUND: Approximately half of Americans have inadequate health literacy,
      which leads to poorer health outcomes. Health numeracy is an important component
      of literacy, which reflects one's ability to understand and manipulate numbers.
      This is especially important for transplant candidates, as adherence to medical
      recommendations is essential for posttransplant care. Although validated measures
      of numeracy exist, they can be inconvenient and time consuming to administer.
      METHODS: The brief medical numbers test (BMNT) was created in 2011 to quickly
      assess the health numeracy of a patient during presurgical psychiatric transplant
      evaluations. The purpose of this study was to evaluate the reliability and
      validity of the BMNT for this use via retrospective chart review. There were 293
      patients referred over a 2-year period for a presurgical psychiatric evaluation.
      The evaluation consisted of a semistructured interview and completion of several
      measures, including the BMNT, a measure of health literacy, and a brief test of
      cognitive functioning. RESULTS: The BMNT had acceptable internal consistency
      (alpha = .71), convergent validity with health literacy and cognitive
      functioning, and predictive validity with surgical outcomes. CONCLUSIONS:
      Preliminary data suggests the BMNT is a reliable and valid measure of health
      numeracy in patients being evaluated for transplant.

PMID- 30093242
TI  - Fibroids and Antipsychotics.

PMID- 30093243
TI  - Autoimmune Encephalopathy Beyond Anti-NMDAR Encephalitis: The Case of an
      Adolescent Male with AntiAcetylcholine Receptor Ganglionic Neuronal Antibody
      Encephalitis.

PMID- 30093244
TI  - A Survey of Clinical Approaches to Suicide Risk Assessment for Patients
      Intoxicated on Alcohol.
AB  - INTRODUCTION: Suicidal ideation and alcohol use are common among emergency
      department patients. It is unclear at what point a suicide risk assessment should
      occur among patients who present with acute alcohol intoxication. This study aims
      to describe practice patterns among expert practitioners for timing the suicide
      risk assessment for an intoxicated patient. METHODS: An online survey was sent to
      emergency psychiatrists and behavioral health specialists on 2 national
      listserves including that of the Academy of Consultation-Liaison Psychiatry's
      Emergency Psychiatry Special Interest Group. RESULTS: Sixty respondents had a
      mean of 16 +/- 12 years (mean +/- standard deviation) out of specialty training
      and had extensive experience and comfort in managing this patient presentation.
      All respondents were board-certified and most (68%) practiced in academic
      settings. The most common practice for conducting a safety risk assessment in
      alcohol intoxicated patients was to proceed once the patient was clinically sober
      (58%). Other practices included retesting the patient until a specific blood
      alcohol concentration was reached (19%) or waiting a certain time after
      presentation based on the initial blood alcohol concentration (15%). Some (8%)
      evaluated actively intoxicated patients for suicide risk. Practice varied
      slightly based on the location of practice, type of practice, and where the
      clinician trained. DISCUSSION: Expert clinicians most often describe using a
      clinical assessment to determine sobriety before completing a suicidal risk
      assessment, although alternative practices remain common. While advantages and
      disadvantages vary among different approaches, the quality and evidence base
      underlying these practices are questioned.

PMID- 30093245
TI  - Low Plasma Cholinesterase Activity is Associated With Postoperative Delirium
      After Noncardiac Surgery in Elderly Patients: A Prospective Observational Study.
AB  - BACKGROUND: Postoperative delirium (POD) commonly occurs in elderly patients
      after noncardiac surgery, resulting in increased morbidity and greater risk of
      death. However, its pathophysiology is currently unknown. Cholinergic dysfunction
      has been implicated in delirium pathophysiology, and low plasma cholinesterase
      activity has been reported as a risk marker of POD. Therefore, the aim of this
      study was to investigate the link between plasma cholinesterase activity and POD
      in elderly Han Chinese patients after noncardiac surgery. METHOD: From January
      2014 to January 2016, a cohort of 206 patients aged >= 60 years who underwent
      noncardiac surgery and were transferred to the surgical intensive care unit were
      enrolled. POD was assessed using the Confusion Assessment Method for Intensive
      Care Unit. Clinical data including sex, age, general comorbidities, alcohol
      consumption, Acute Physiology and Chronic Health Evaluation II score, and type of
      surgery were recorded. Blood was drawn postoperatively to measure cholinesterase
      activity. Using multiple logistic regression analyses, the associations between
      cholinesterase activity and POD were examined, adjusting for potential
      confounding variables. RESULTS: Delirium incidence was 22.3%. POD was associated
      with cholinesterase activity, age, and Acute Physiology and Chronic Health
      Evaluation II score. In multiple logistic regression analyses, lower
      acetylcholinesterase and butyrylcholinesterase activity was independent risk
      factors for POD. CONCLUSION: Plasma cholinesterase activity may be a candidate
      biomarker for POD after noncardiac surgery in the elderly Chinese Han population.

PMID- 30093246
TI  - Treatment and prevention of bleeding in congenital hemophilia A patients with
      inhibitors.
AB  - The treatment of bleeding in hemophilia A patients with persistent inhibitory
      antibodies to factor VIII is problematic. The current standard hemostatic agents
      for inhibitor patients are recombinant activated factor VII (rFVIIa) and
      activated prothrombin complex concentrate (APCC). These "inhibitor bypassing
      agents" are less reliably effective than are replacement therapies for patients
      without inhibitors, and there are no validated laboratory assays to monitor their
      efficacy. Furthermore, only single rFVIIa and APCC products are available
      worldwide, and their use can be complicated, albeit rarely, by thrombotic events.
      For all these reasons, new approaches to treat bleeding in inhibitor patients are
      eagerly awaited. These new approaches include replacement therapy with porcine
      factor VIII concentrate (currently approved for use in acquired hemophilia
      patients), bispecific antibodies to simulate the biologic function of factor VIII
      (already in use in some jurisdictions), pegylated forms of activated factor VII,
      and strategies targeting the natural anticoagulants TFPI and antithrombin, which
      create a hypercoagulable phenotype to counterbalance the hypocoagulability
      imposed by hemophilia.

PMID- 30093247
TI  - Recent advances in clinical use of mesenchymal stem cells in Japan.

PMID- 30093248
TI  - Novel assays in the coagulation laboratory: a clinical and laboratory
      perspective.
AB  - The ability to monitor Factor VIII (FVIII) and Factor IX (FIX) levels is integral
      to the clinical management of hemophilia A and B patients, respectively. Factor
      activity levels are checked during regular follow-up, post-infusion of factor
      concentrates, during pre- and post-operative assessments, and when the presence
      of an inhibitor is suspected. However, the ability to accurately and reproducibly
      measure factor activity levels with standard coagulation assays has been
      challenging due to the emergence of recombinant factor concentrates with extended
      half-lives. Similarly, special considerations must be given to the type of
      inhibitor assay used in patients with acquired hemophilia receiving recombinant
      porcine FVIII replacement. Alternative approaches to achieve hemostasis with
      clotting factor mimetics and interference of endogenous anticoagulants lack
      standardized assays for monitoring hemostatic efficacy. Laboratory assays
      measuring dynamic clotting parameters such as thrombin generation or whole blood
      viscoelasticity may provide a way forward, but have yet to enter routine clinical
      use. This review highlights the role of specialized coagulation assays in an era
      where multiple new hemostatic therapeutics for hemophilia are available, and
      underscores the need for clear communication between bedside and laboratory
      clinicians.

PMID- 30093250
TI  - Harry T Orr: decoding spinocerebellar ataxias.

PMID- 30093249
TI  - Evaluation of TDP-43 proteinopathy and hippocampal sclerosis in relation to APOE
      epsilon4 haplotype status: a community-based cohort study.
AB  - BACKGROUND: Transactive response DNA-binding protein of 43 kDa (TDP-43)
      proteinopathy in older adults frequently coexists with Alzheimer's disease
      pathology and hippocampal sclerosis. It is unclear whether there is a link
      between APOE epsilon4 and TDP-43 proteinopathy, and the role of APOE epsilon4 in
      the association of TDP-43 proteinopathy with hippocampal sclerosis remains to be
      examined. We investigated the relationships of TDP-43 proteinopathy and
      hippocampal sclerosis with APOE epsilon4. METHODS: We used data from two
      community-based cohort studies of ageing and dementia: the Religious Orders Study
      (ROS) and the Rush Memory and Aging Project (MAP). A battery of cognitive tests
      examining multiple cognitive domains is given to ROS-MAP participants each year,
      and a measure of annual global cognitive function for each participant is derived
      by averaging Z scores of these tests. The final clinical diagnosis is assigned
      after death by a neurologist using all available clinical data without access to
      post-mortem pathology. Amyloid-beta, paired helical filament tau, Lewy bodies,
      TDP-43, and hippocampal sclerosis were microscopically evaluated in the midbrain,
      medial temporal, and neocortical regions that capture the progression of each
      neuropathology. TDP-43 proteinopathy topographic stage was recorded as an ordinal
      variable, and TDP-43 burden was defined by averaging a semi-quantitative six
      point scale across six brain regions. The relationships among APOE epsilon4, TDP
      43 proteinopathy, and hippocampal sclerosis were tested with regression models
      controlled for sex and age at death, and they were further explored with a
      mediation analysis using the quasi-Bayesian Monte Carlo method. FINDINGS: ROS
      began data collection in 1994, and MAP began data collection in 1997. The data
      included in this study were analysed from Jan 16, 2017, to July 12, 2017. When
      analysis began in January, 2017, a total of 1059 ROS-MAP participants who were
      deceased had APOE genotype and complete pathological measures for amyloid-beta,
      paired helical filament tau, and TDP-43 proteinopathy stage. After excluding 15
      participants with other pathological diagnoses, 1044 participants, 1042 of whom
      also had measures of Lewy body pathology, were included in this study (470 from
      ROS and 574 from MAP). APOE epsilon4 count was associated with higher TDP-43
      proteinopathy stage (odds ratio [OR] 2.0, 95% CI 1.6-2.6; p=1.9 * 10-9) and TDP
      43 burden (0.40, 0.28-0.52; p=1.2 * 10-10). Amyloid-beta, paired helical filament
      tau, or Lewy body pathology did not fully explain this association. APOE epsilon4
      increased the odds of hippocampal sclerosis (OR 2.1, 95% CI 1.4-3.0; p=1.7 * 10
      4); this effect was largely mediated by TDP-43 burden (mediated effect p<1.0 * 10
      4) but not directly by APOE epsilon4 (direct effect p=0.40). APOE epsilon4 was
      associated with worse global cognition proximate to death even after adjusting
      for amyloid-beta and paired helical filament tau (estimated effect -0.18, 95% CI 
      0.31 to -0.04; p=0.010), but this association was attenuated by additionally
      adjusting for TDP-43 burden (-0.09, -0.22 to 0.04; p=0.18). INTERPRETATION: APOE
      epsilon4 seems to increase TDP-43 burden, and this effect in turn was associated
      with higher odds of hippocampal sclerosis, a pathology potentially downstream of
      TDP-43 proteinopathy. TDP-43 proteinopathy contributes to the detrimental effect
      of APOE epsilon4 on late-life cognition through mechanisms independent of
      Alzheimer's disease pathology, and future research should consider that TDP-43
      proteinopathy might be an integral component of APOE-related neurodegeneration.
      FUNDING: US National Institute on Aging and Alzheimer's Association.

PMID- 30093251
TI  - Fitting TDP-43 into the APOE epsilon4 and neurodegeneration story.

PMID- 30093252
TI  - Monitoring the pulse of thrombus formation: Comment on "Modeling thrombosis in
      silico: Frontiers, challenges, unresolved problems and milestones" by A.V.
      Belyaev et al.

PMID- 30093253
TI  - Mining heterogeneous networks with topological features constructed from patient
      contributed content for pharmacovigilance.
AB  - Drug safety, also called pharmacovigilance, represents a serious health problem
      all over the world. Adverse drug reactions (ADRs) and drug-drug interactions
      (DDIs) are two important issues in pharmacovigilance, and how to detect drug
      safety signals has drawn many researchers' attention and efforts. Currently,
      methods proposed for ADR and DDI detection are mainly based on traditional data
      sources such as spontaneous reporting data, electronic health records,
      pharmaceutical databases, and biomedical literature. However, these data sources
      are either limited by under-reporting ratio, privacy issues, high cost, or long
      publication cycle. In this study, we propose a framework for drug safety signal
      detection by harnessing online health community data, a timely, informative, and
      publicly available data source. Concretely, we used MedHelp as the data source to
      collect patient-contributed content based on which a weighted heterogeneous
      network was constructed. We extracted topological features from the network,
      quantified them with different weighting methods, and used supervised learning
      method for both ADR and DDI signal detection. In addition, after identifying DDI
      signals, we proposed a new metric, named Interaction Ratio, to identify
      associated ADRs due to suspected interactions. The experiment results showed that
      our proposed techniques outperforms baseline methods.

PMID- 30093254
TI  - French Society of Cardiology guidelines on exercise tests (part 1): Methods and
      interpretation.
AB  - The exercise test is still a key examination in cardiology, used for the
      diagnosis of myocardial ischemia, as well as for the clinical evaluation of other
      heart diseases. The cardiopulmonary exercise test can further define functional
      capacity and prognosis for any given cardiac pathology. These new guidelines
      focus on methods, interpretation and indications for an exercise test or
      cardiopulmonary exercise test, as summarized below. The safety rules associated
      with the exercise test must be strictly observed. Interpretation of exercise
      tests and cardiopulmonary exercise tests must be multivariable. Functional
      capacity is a strong predictor of all-cause mortality and cardiovascular events.
      Chest pain, ST-segment changes and an abnormal ST/heart rate index constitute the
      first findings in favor of myocardial ischemia, mostly related to significant
      coronary artery disease. Chronotropic incompetence, abnormal heart rate recovery,
      QRS changes (such as enlargement or axial deviations) and the use of scores
      (based on the presence of various risk factors) must also be considered in
      exercise test interpretation for a coronary artery disease diagnosis. Arrhythmias
      or conduction disorders arising during the exercise test must be considered in
      the assessment of prognosis, in addition to a decrease or low increase in blood
      pressure during the exercise phase. When performing a cardiopulmonary exercise
      test, peak oxygen uptake and the volume of expired gas/carbon dioxide output
      slope are the two main variables used to evaluate prognosis.

PMID- 30093255
TI  - French Society of Cardiology guidelines on exercise tests (part 2): Indications
      for exercise tests in cardiac diseases.
AB  - The exercise test is performed routinely in cardiology; its main indication is
      the diagnosis of myocardial ischemia, evaluated along with the subject's pretest
      probability and cardiovascular risk level. Other criteria, such as analysis of
      repolarization, must be taken into consideration during the interpretation of an
      exercise test, to improve its predictive value. An exercise test is also
      indicated for many other cardiac diseases (e.g. rhythm and conduction disorders,
      severe asymptomatic aortic stenosis, hypertrophic cardiomyopathy, peripheral
      artery disease, hypertension). Moreover, an exercise test may be indicated for
      specific populations (women, the elderly, patients with diabetes mellitus,
      patients in a preoperative context, asymptomatic patients and patients with
      congenital heart defects). Some cardiac diseases (such as chronic heart failure
      or arterial pulmonary hypertension) require a cardiopulmonary exercise test.
      Finally, an exercise test or a cardiopulmonary exercise test is indicated to
      prescribe a cardiac rehabilitation programme, adapted to the patient.

PMID- 30093256
TI  - Comparison of short and long-time outcomes between laparoscopic and conventional
      open multivisceral resection for primary T4b colorectal cancer.
AB  - BACKGROUND: This study aimed to compare laparoscopic multivisceral resection
      (LMVR) with conventional open multivisceral resection (OMVR) for primary T4b
      colorectal cancer (CRC) in short and long-time outcomes. METHODS: Patients
      receiving LMVR or OMVR for primary T4b CRC from January 2009 to June 2016 were
      enrolled. Patients' clinicopathological characteristics and survival data were
      collected and analyzed. Multivariable analysis was performed to find the factors
      related with survival. All statistical analysis was performed by SPSS 22.0.
      RESULTS: A total of 91 patients (LMVR 38, OMVR 53) were included in this study.
      Patients undergoing LMVR were associated with smaller incision length (P <
      0.001), less blood loss (P = 0.01) and comparable operative time (P = 0.071).
      Patients in LMVR group also had less time to first flatus (P = 0.025). The
      results also suggested LMVR could reduce the incidence of postoperative
      complication. The conversion rate was 28.9%. The 3-year OS was 64.2%, 68.4% in
      OMVR, LMVR group respectively and the 3-year DFS was 56.6%, 52.6% in OMVR, LMVR
      group respectively. The Kaplan curves demonstrated that LMVR group had similar OS
      (P = 0.896) and DFS (P = 0.806) when compared with OMVR group. In addition, the
      multivariate analysis demonstrated that laparoscopic surgery was not associated
      with poorer survival. CONCLUSION: Not all MVR for T4b CRC should be performed by
      open procedure, LMVR can be safe and feasible for primary T4b CRC in selected
      patients. It can faster the postoperative recovery and reduce the incidence of
      postoperative complication. The OS and DFS are also not inferior to open group.

PMID- 30093258
TI  - Tai Chi may be More Effective for Improving Fibromyalgia Symptoms Than Aerobic
      Exercise.

PMID- 30093257
TI  - The role of RENAL, PADUA and C-index scoring systems in predicting the results of
      partial nephrectomy without ischemia.
AB  - OBJECTIVE: To evaluate the feasibility and renoprotective effect of off-clamp
      partial nephrectomy (PN) by renal scoring systems. METHODS: After approval of the
      local ethics committee, the radiological and clinical data of patients with renal
      masses who underwent PN between January 2012 and January 2017 were evaluated in
      two university hospitals. Total 132 patients who underwent open surgery and off
      clamp technique were included. All patients underwent contrast-enhanced computed
      tomography (CT) or magnetic resonance imaging (MRI) preoperatively. Preoperative
      demographic data, estimated glomerular filtration rate (e-GFR) and hematocrit
      changes, operation time, tumor volume and hospitalization time from patients were
      evaluated separately and statistically for each of the three scoring systems.
      RESULTS: Our study consisted of 132 patients with a mean age of 53.9 +/- 13.9
      with 69 male and 63 female. Statistically significant difference between the risk
      groups in RENAL and PADUA scoring were found according to tumor T stage and tumor
      volume (p <0.005). Statistically significant difference was only found between
      risk groups of RENAL scoring system in e-GFR reduction (p<0.05). There was no
      statistically significant difference between the groups in the complications of
      all three classification systems (p > 0.005). CONCLUSIONS: In our study, all
      three scoring sytem successfully predicted the surgical complexity ve surgical
      outcomes and our results indicate that off-clamp PN has similar success and
      complications rates when compared to the literature. The off-clamp PN must be
      kept in mind to maintain postoperative renal functions eligible patients.

PMID- 30093259
TI  - Prenatal renal parenchymal area as a predictor of early end-stage renal disease
      in children with vesicoamniotic shunting for lower urinary tract obstruction.
AB  - BACKGROUND: Vesicoamniotic shunting (VAS) and other bladder drainage techniques
      for fetal lower urinary tract obstruction (LUTO) have been proven to ameliorate
      pulmonary hypoplasia and increase survival in patients with an initial poor
      prognosis. Currently there are limited prognostic tools available during
      gestation to evaluate and predict postnatal renal function. OBJECTIVE: The aim
      was to describe the prenatal growth of the renal parenchymal area (RPA) in
      patients with LUTO and determine its application as a predictor of renal function
      at one year of life. STUDY DESIGN: The study population comprised a retrospective
      cohort of all infants who survived the fetal VAS to birth. Renal growth and size
      were measured using imageJ software to calculate the RPA in sequential prenatal
      ultrasounds. The parenchymal area was measured from the image of each kidney with
      the greatest longitudinal length. These measurements were further correlated and
      analyzed as a predictor of end-stage renal disease (ESRD) within the first year
      of life. RESULTS: Etiologies of LUTO in the 15 male fetuses included eight
      posterior urethral valves, four Eagle-Barrett/prune belly syndrome, two urethral
      atresia, and one megacystis microcolon intestinal hypoperistalsis syndrome. All
      patients had patent shunts, in place, at birth. Furthermore, ultrasonographic
      parameters such as oligohydramnios, keyhole sign, and bladder wall thickness
      showed no statistical difference between groups. Renal parenchymal growth
      correlated with postnatal renal function in both the ESRD (r = 0.409, p = 0.018)
      and the non-ESRD (r = 0.657, p < 0.001) groups. Most notably, RPA during the 3rd
      trimester predicted ESRD with the best cut-off point determined to be 8 cm2
      (sensitivity, 0.714; specificity, 0.882; and positive likelihood ratio, 6.071)
      (Table). DISCUSSION: Despite definitive VAS for LUTO, postnatal morbidity and
      mortality remain high, emphasizing the role of renal dysplasia in postnatal renal
      failure, in spite of urinary diversion. Renal growth statistically differs
      between groups in the 3rd trimester of gestation; RPA development appears
      stagnant in patients that developed ESRD within the first year of life. In
      contrast, patients that did not develop ESRD continued to have renal parenchymal
      growth in a linear fashion. This suggests that prenatal RPA may be predictive of
      postnatal ESRD. CONCLUSIONS: RPA measurement during the prenatal period could
      play an important role as a non-invasive tool to predict postnatal renal function
      and to anticipate postnatal clinical interventions.

PMID- 30093260
TI  - The visual guidance of action is not insulated from cognitive interference: A
      multitasking study on obstacle-avoidance and bisection.
AB  - The Perception-Action Model (PAM) considers the visual system to be divided into
      two streams defined by their specific functions, a ventral stream for vision and
      a dorsal stream for action. In this study we investigated two behavioral
      paradigms which according to PAM represent the two contrasting functions of the
      ventral and dorsal stream, namely bisection and obstacle-avoidance, respectively.
      It is an assumption of PAM that while ventral stream processing is ultimately
      linked with processing in other cognitive systems, dorsal stream processing is
      insulated from cognition. Accordingly it can be expected that a secondary task
      will interfere with bisection but not with obstacle-avoidance. We tested this
      prediction using a rapid serial visual presentation task as our secondary task
      (RSVP). Contrary to expectations we found significant interference for both
      bisection and obstacle-avoidance. Our findings suggest that dorsal-stream
      processing is not insulated from cognitive processes.

PMID- 30093261
TI  - The relationships between improvements in daytime sleepiness, fatigue and
      depression and psychomotor vigilance task testing with CPAP use in patients with
      obstructive sleep apnea.
AB  - OBJECTIVE: The purpose of this study was to determine if the subjective
      improvements in daytime sleepiness, fatigue and depression experienced by
      patients with obstructive sleep apnea (OSA) with continuous positive airway
      pressure (CPAP) therapy predict an objective improvement in vigilance, and
      whether patients with mild-to-moderate OSA differ from patients with severe OSA
      in this regard. METHODS: A total of 182 patients underwent psychomotor vigilance
      task (PVT) testing and measurements of subjective daytime sleepiness, fatigue and
      depression at baseline and after a minimum of one month of adherent CPAP use at
      an adequate pressure. RESULTS: Patients with both mild-to-moderate (n = 92) and
      severe (n = 90) OSA experienced improvements in subjective daytime sleepiness,
      fatigue and depression, but objective improvement in vigilance was only seen in
      patients with severe OSA. In patients with severe OSA, while a correlation was
      found between improvements in daytime sleepiness and some PVT parameters, changes
      in subjective daytime sleepiness, fatigue and depression scores were not
      predictive of objective improvement in vigilance while controlling for all these
      subjective symptoms and for age, gender, body mass index, apnea-hypopnea
      index/respiratory event index and total sleep time/total recording time with
      pulse oximetry below 90%. CONCLUSIONS: We found no predictive relationship
      between subjective improvements in daytime sleepiness, fatigue and depression and
      objective vigilance with CPAP use in patients with OSA. These results suggest
      that subjective complaints of daytime impairment and objective measures of
      vigilance in patients with OSA should be assessed separately while evaluating the
      efficacy of CPAP therapy on daytime functioning.

PMID- 30093262
TI  - Difference in severity of sleep apnea in patients with rapid eye movement sleep
      behavior disorder with or without parkinsonism.
AB  - OBJECTIVE: Rapid eye movement sleep behavior disorder (RBD) is a common sleep
      disturbance in patients with neurodegenerative disorders. We aimed to compare
      sleep parameters among the different types of RBD patients. METHODS: A total of
      122 patients with dream enactment behavior were screened. Of these, 92 patients
      who were diagnosed with RBD by polysomnography were included in this study.
      Enrolled patients with RBD were classified into four groups based on the
      following diagnoses: idiopathic RBD (iRBD); RBD with Parkinson disease (PD-RBD);
      multiple system atrophy (MSA) with RBD (MSA-RBD); and dementia with Lewy bodies
      (DLB) with RBD (DLB-RBD). Various clinical and polysomnographic parameters were
      compared. RESULTS: Among the 92 patients with RBD, 35 had iRBD, 25 had PD-RBD, 17
      had MSA-RBD, and 15 had DLB-RBD. The mean apnea-hypopnea index of atypical
      parkinsonism with RBD (AP-RBD) group was 16.2 +/- 17.7 events/h (MSA-RBD, 14.0 +/
      16.6; DLB-RBD, 18.8 +/- 19.1), which was significantly higher than the other
      groups (p < 0.05). The proportion of patients with 100% supine sleep in the AP
      RBD group (44%) was higher than that in the iRBD group (14%; p = 0.030). The
      proportion of OSA with 100% supine sleep position was significantly higher in the
      MSA-RBD and DLB-RBD groups than in the iRBD group (p = 0.042 and p = 0.029,
      respectively). CONCLUSION: Our study demonstrated that patients in the MSA-RBD
      and DLB-RBD groups had a tendency to sleeping in the supine position and a higher
      vulnerability to OSA compared to other RBD groups. Further cohort studies are
      needed to evaluate the influence of these factors on the development of
      parkinsonism.

PMID- 30093263
TI  - Negative Lymph Node Count and Lymph Node Ratio Are Associated With Survival in
      Male Breast Cancer.
AB  - BACKGROUND: Male breast cancer (MBC) is usually diagnosed at late stages and
      therefore has a worse prognosis than female breast cancer (FBC). MBC is also more
      likely to have lymph node (LN) involvement than FBC. MATERIALS AND METHODS: We
      sought to determine the prognostic role of the examined lymph node (LN), negative
      LN (NLN), and positive LN counts and the LN ratio (LNR), defined as (positive
      LNs/ENLs), on the survival rate among MBC patients. We performed a large
      population-based study using the data from the Surveillance, Epidemiology, and
      End Results program. RESULTS: Older age, black race, stage IV disease, <= 1 NLN,
      and a > 31.3% LNR were significantly associated with worse survival across all
      prediction models. Moreover, we demonstrated a decreased risk of mortality in MBC
      patients across the MBC-specific survival model (hazard ratio, 0.98; 95%
      confidence interval, 0.96-0.998; P = .03) and 10-year MBC-specific survival model
      (hazard ratio, 0.98; 95% confidence interval, 0.96-0.999; P = .04). CONCLUSION:
      MBC has had an augmented incidence over the years. We found several independent
      predictors of MBC survival, including age, race, stage, NLNs, and the LNR. We
      strongly suggest adding the NLN count and/or LNR into the current staging system.
      Further studies are needed to provide information on the mechanisms underlying
      the association between the NLN count and MBC survival and the LNR and MBC
      survival.

PMID- 30093264
TI  - Culturing Periprosthetic Joint Infection: Number of Samples, Growth Duration, and
      Organisms.
AB  - BACKGROUND: Owing to the difficulty isolating microorganisms in periprosthetic
      joint infection (PJI), current guidelines recommend that 3-5 intraoperative
      samples be cultured and maintained for 3-14 days. We investigated (1) the optimal
      number of culture samples and growth duration to diagnose PJI and (2) the
      microbiology profile at our institution. METHODS: A retrospective review of 711
      patients (329 hips, 382 knees) with PJI that met Musculoskeletal Infection
      Society criteria from 2000 to 2014 was performed. Two thousand two hundred ninety
      aerobic and anaerobic cultures were analyzed. A manual chart review collected
      demographic, surgical, and microbiological data. Microbiology profiles were
      trended. Logistic regression analysis was performed to determine statistical
      significance. RESULTS: Obtaining 5 samples provided the greatest yield positive
      cultures for diagnosing PJI. The percentage of positive cultures overall was
      62.6% and stratified by organism type: antibiotic resistant (80.0%),
      Staphylococcus aureus (76.0%), gram negative (58.9%), Pseudomonas (52.0%),
      variant PJI organisms (28.2%), Propionibacterium acnes (20.0%), and Escherichia
      coli (8.0%). Although most organisms were cultured in 5 days or less, 10.8 days
      were needed for Propionibacterium acnes, 6.6 for variant PJI organisms, and 5.2
      for coagulase-negative Staphylococcus. At 3 days, only 42.2% of cultures turned
      positive compared with 95.0% at 8 days. There was a significant decrease in time
      in gram-positive PJIs and an increase in culture-negative PJIs. CONCLUSION: The
      optimal number of cultures and growth duration depended on the type of organism.
      This study provides evidence that 5 samples should be obtained and held for at
      least 8 days given that the type of organisms is likely to be unknown at the time
      of surgery.

PMID- 30093265
TI  - Validation of a Novel Surgical Data Capturing System Following Total Hip
      Arthroplasty.
AB  - BACKGROUND: The OrthoMiDaS (Orthopedic Minimal Data Set) Episode of Care (OME)
      database was developed in an effort to advance orthopedic outcome measurements on
      a national scale. This study was designed to evaluate if the OME data capture
      system would increase the quality of data collected in the context of primary and
      revision total hip arthroplasty (THA) compared to conventional operative notes.
      METHODS: This study includes data from the first 100 primary THAs and 100
      revision THAs performed by 15 surgeons at a single institution from January
      through April 2016. Surgeons prospectively entered procedural details into OME
      following surgery. The OME database and operative notes were compared to evaluate
      completion rates and agreement. Completion rates were compared using McNemar's
      test (with continuity correction), while agreement was analyzed using Cohen's
      kappa (kappa) and concordance correlation coefficient. RESULTS: The OME database
      had significantly higher completion rates for 41% (39/96) of the variables.
      Proportion of data points that matched between the operative notes and OME data
      revealed that 54% (52/96) had a proportion agreement >0.90, and 79% (76/96) had a
      proportion agreement >0.80. In regard to measured agreement, 25% (24/96) of
      variables had almost perfect agreement, 29% (28/96) had substantial agreement,
      and 14% (13/96) had moderate agreement. Only 4% (4/96) had fair agreement, 8%
      (8/96) had slight agreement, and 6% (6/96) had poor agreement. CONCLUSION: The
      OME data capture system is an efficient tool to document procedural details
      following THA. The system is user-friendly, comprehensive, and accurate. It has
      the potential to be a valuable tool for future orthopedic research.

PMID- 30093266
TI  - Cefazolin Prophylaxis for Total Joint Arthroplasty: Obese Patients Are Frequently
      Underdosed and at Increased Risk of Periprosthetic Joint Infection.
AB  - BACKGROUND: One of the most effective prophylactic strategies against
      periprosthetic joint infection (PJI) is administration of perioperative
      antibiotics. Many orthopedic surgeons are unaware of the weight-based dosing
      protocol for cefazolin. This study aimed at elucidating what proportion of
      patients receiving cefazolin prophylaxis are underdosed and whether this
      increases the risk of PJI. METHODS: A retrospective study of 17,393 primary total
      joint arthroplasties receiving cefazolin as perioperative prophylaxis from 2005
      to 2017 was performed. Patients were stratified into 2 groups (underdosed and
      adequately dosed) based on patient weight and antibiotic dosage. Patients who
      developed PJI within 1 year following index procedure were identified. A
      bivariate and multiple logistic regression analyses were performed to control for
      potential confounders and identify risk factors for PJI. RESULTS: The majority of
      patients weighing greater than 120 kg (95.9%, 944/984) were underdosed.
      Underdosed patients had a higher rate of PJI at 1 year compared with adequately
      dosed patients (1.51% vs 0.86%, P = .002). Patients weighing greater than 120 kg
      had higher 1-year PJI rate than patients weighing less than 120 kg (3.25% vs
      0.83%, P < .001). Patients who were underdosed (odds ratio, 1.665; P = .006) with
      greater comorbidities (odds ratio, 1.259; P < .001) were more likely to develop
      PJI at 1 year. CONCLUSION: Cefazolin underdosing is common, especially for
      patients weighing more than 120 kg. Our study reports that underdosed patients
      were more likely to develop PJI. Orthopedic surgeons should pay attention to the
      weight-based dosing of antibiotics in the perioperative period to avoid
      increasing risk of PJI.

PMID- 30093267
TI  - A comment on "Antigenic analysis of genetic variants of Canine distemper virus".

PMID- 30093268
TI  - Using shared governance to achieve a culture change in safe patient handling.

PMID- 30093269
TI  - P2X7 Receptor: A Potential Therapeutic Target for Depression?
AB  - Depression is a prime contributor to global disease burden with 300 million
      affected patients worldwide. The persistent lack of progress with regards to
      pharmacotherapy stands in stark contrast to the pandemic magnitude of the
      disease. Alterations of inflammatory pathways in depressed patients, including
      altered circulating pro-inflammatory cytokines, have been put forward as a
      potential pathophysiological mechanism. The P2X7 receptor (P2X7R) plays an
      important role regulating the release of interleukin-1beta and other cytokines.
      Comprehensive investigation of the P2X7R Gln460Arg missense mutation (rs2230912),
      which has been associated with major depression and bipolar disorder, has
      substantially contributed to validate P2X7R as a potential genetic risk factor.
      We propose that P2X7R is a putative target with good prospects for therapeutic
      intervention in depressive disorders.

PMID- 30093270
TI  - Navigated transcranial magnetic stimulation for preoperative cortical mapping of
      expressive language in children: Development of a method.
AB  - We adjusted an object-naming task with repetitive navigated transcranial magnetic
      stimulation (rnTMS) originally developed for preoperative cortical language
      mapping in adults in order for it to be used in children. Two series of pictures
      were chosen for children above and below 10 years of age, respectively. Firstly,
      the series of pictures and the preferred speed of presentation were assessed for
      their applicability in children of different ages and abilities. Secondly, these
      series were used with rnTMS preoperatively in five children with epilepsy. Naming
      errors induced by the stimulation comprised no response, delayed response,
      semantic error, phonological error, and self-correction. Language laterality was
      compared with the results of a dichotic listening test and with
      neuropsychological tests with respect to general laterality, and general language
      abilities were considered with respect to the results of stimulation. One
      participant had below normal general language abilities, two had below-normal
      rapid naming, and three had slow and indistinct articulation. Laterality was only
      clear in two of the participants. All children required breaks of various
      durations during the process, and individual adjustments of the interpicture
      interval and other stimulation parameters were also made. We conclude that, after
      adjustment, rnTMS combined with an object-naming task can be useful for
      preoperative language mapping in children.

PMID- 30093271
TI  - Usefulness of Trabecular Bone Score (TBS) to Identify Bone Fragility in Patients
      with Primary Hyperparathyroidism.
AB  - BACKGROUND: Patients with primary hyperparathyroidism usually show decreased bone
      strength that are often not well diagnosed by conventional Dual-energy X-ray
      absorptiometry (DXA). Trabecular Bone Score (TBS) is a new technique for
      assessing bone microarchitecture indirectly. This cross-sectional study evaluates
      the usefulness of TBS in patients with primary hyperparathyroidism in clinical
      practice. METHODOLOGY: Bone mineral density (BMD) by DXA and TBS values by TBS
      InSight(r) software were determined in 72 patients with primary
      hyperparathyroidism to analyze its relationship with fragility fractures. A
      receiver operating curve was performed to evaluate the usefulness of TBS as
      predictor of fragility fractures. FRAX index with and without adjustment by TBS
      was calculated. Additionally, longitudinal data of a subgroup of patients
      according to the therapeutic management were also evaluated. RESULTS: A total of
      51.4% of the patients showed degraded microarchitecture while only 37.5% of them
      were diagnosed of osteoporosis by DXA. No significant correlation was found
      between TBS values and BMD parameters. However, TBS values were lower in
      osteoporotic patients compared to those classified as normal by BMD (1.16 +/-
      0.12 vs 1.26 +/- 0.17; p = 0.043) and in patients with fragility fractures
      compared to nonfractured patients (1.19 +/- 0.03 vs 1.24 +/- 0.02, p < 0.001).
      The area under the curve for TBS performed better than the combination of
      femoral, hip and spine-BMD for prevalent fractures (0.714 vs 0.679). TBS-adjusted
      FRAX was higher than nonadjusted model for both major osteoporotic and hip
      fracture (4.5% vs 3%; 0.9% vs 0.7%; p < 0.001). At follow-up, an improvement in
      TBS values was observed in treated patients (medical or surgical) vs nontreated
      close to significance (1.27 +/- 0.10 vs 1.24 +/- 0.11, p = 0.074). CONCLUSIONS:
      TBS could be a useful tool to identify increased fracture risk in patients with
      primary hyperparathyroidism underdiagnosed by BMD. Moreover, FRAX adjusted by TBS
      could be a more robust tool for predicting the risk of osteoporotic fracture to
      help in therapeutic decisions in this population.

PMID- 30093272
TI  - Growth velocity of the portal vein tumor thrombus accelerated by its progression,
      alpha-fetoprotein level, and liver fibrosis stage in patients with hepatocellular
      carcinoma.
AB  - BACKGROUND: Progression of portal vein tumor thrombus directly affects the
      prognosis and treatment for patients with hepatocellular carcinoma; there are no
      data on the growth velocity of portal vein tumor thrombus. We analyzed the growth
      velocity of portal vein tumor thrombus and its risk factors to propose the best
      timing of surgical treatment for hepatocellular carcinoma with portal vein tumor
      thrombus. METHODS: We retrospectively collected data on 57 hepatocellular
      carcinoma patients with portal vein tumor thrombus who underwent computed
      tomography twice preoperatively and hepatectomy between 2005 and 2015. To
      calculate the growth velocity of portal vein tumor thrombus, migration lengths of
      portal vein tumor thrombus were divided by the number of days. To identify risk
      factors for rapid growth of portal vein tumor thrombus, patients were classified
      according to the velocity: rapid (>= 1.0 mm/day, n = 23) and slow (< 1.0 mm/day,
      n = 34). RESULTS: Median survival times of patients with portal vein tumor
      thrombus that invaded the ipsilateral second portal branch, ipsilateral first
      portal branch, and portal trunk were 42.9, 11.7, and 12.3 months, respectively.
      The average growth velocity of portal vein tumor thrombus was 0.9 +/- 1.0 mm/day.
      Median estimated times required from ipsilateral second portal branch to
      ipsilateral first portal branch and ipsilateral first portal branch to portal
      trunk were 8.2 and 11.5 days, respectively. Liver fibrosis, alpha-fetoprotein,
      and extent of portal vein tumor thrombus were independent risk factors for rapid
      progression of portal vein tumor thrombus. Proteins induced by vitamin K absence
      or antagonist II, extent of portal vein tumor thrombus, and liver fibrosis, not
      rapid growth of portal vein tumor thrombus, were independent prognostic factors.
      CONCLUSION: An understanding of the rapid progression of portal vein tumor
      thrombus and its risk factors can be helpful in deciding an appropriate timing of
      surgical treatment for hepatocellular carcinoma with portal vein tumor thrombus.

PMID- 30093273
TI  - Surgeon-associated variation in breast cancer staging with sentinel node biopsy.
AB  - BACKGROUND: Sentinel lymph node biopsy is the gold standard for axillary staging
      in early-stage, clinically node-negative breast cancer, so it is paramount that
      this operation be both precise and accurate, because excessive sentinel lymph
      node removal increases morbidity, whereas understaging risks inadequate
      treatment. The goal of this study was to assess surgeon variation in the number
      of sentinel lymph nodes removed and the oncologic yield of sentinel lymph node
      biopsy for breast cancer. METHODS: All patients in the Surveillance,
      Epidemiology, and End Results-Medicare database who underwent operative treatment
      for breast cancer from 2007-2011 were eligible for inclusion. Deidentified
      provider codes were used to track operations performed by individual surgeons.
      Only records in which an individual surgeon could be linked to a specific breast
      cancer operation were analyzed. The total number of sentinel lymph nodes removed
      and the number that were pathologically positive (oncologic yield) were recorded.
      Surgeon variation by T stage was analyzed using linear mixed-effects regression
      and logistic mixed-effects regression models. RESULTS: Query of the database
      identified 15,571 patients who met inclusion criteria, representing 2,478
      providers. The mean number of sentinel lymph node procedures performed per
      provider per year was 1.3 (range 1-103). The lowest quartile of providers
      performed 1 or fewer sentinel lymph node procedures per year. The highest
      quartile of providers performed >8 sentinel lymph node procedures per year. The
      average number of sentinel lymph node removed per operation increased with
      increasing T stage for all providers (P < .001), including when N0 (P < .001) and
      node-positive (P = .003) patients were evaluated separately. There was surgeon
      associated variation in the number of sentinel lymph node removed for each T
      stage (P < .001). In addition, there was surgeon-associated variation in the
      oncologic yield (sentinel lymph node positivity rate) by T stage (P < .001).
      CONCLUSION: This study found surgeon-associated variation in axillary sentinel
      lymph node staging of breast cancer patients, which suggests the need to improve
      standardization of surgical practices to optimize the oncologic yield of these
      procedures and ensure accurate staging.

PMID- 30093275
TI  - Re: "Long-term follow-up and risk factors for strictures after
      hepaticojejunostomy for bile duct injury: An analysis of surgical and
      percutaneous treatment in a tertiary center".

PMID- 30093274
TI  - Postoperative opioid prescribing practices and the impact of the hydrocodone
      schedule change.
AB  - BACKGROUND: In 2014, hydrocodone was moved from Schedule III to II, thus it could
      no longer be "called in" to a pharmacy. We analyzed current postoperative opioid
      prescribing patterns and the impact of the schedule change on the type and amount
      prescribed. METHODS: Opioid prescriptions for common surgeries at 1 medical
      center from 2013 to 2016 were analyzed retrospectively. Milligram morphine
      equivalents prescribed before and after the schedule change were compared by t
      tests, and interrupted time series models and drug frequencies were compared by
      chi2 and Fisher exact tests. RESULTS: Data from 7,046 patients (7,361
      prescriptions) after 29 different operations were analyzed. Milligram morphine
      equivalents prescribed for minor open procedures ranged from 211 to 342 milligram
      morphine equivalents, from 323 to 1297 for major open procedures, from 238 to 359
      for basic laparoscopic procedures, and from 221 to 868 for complex laparoscopic
      procedures. Mean milligram morphine equivalents prescribed were not affected for
      most procedures, but over the entire population, milligram morphine equivalents
      prescribed began decreasing after the rule change. The percentage of hydrocodone
      prescriptions decreased after the rule change (from 33.8% down to 27.0%) and
      oxycodone and tramadol prescriptions increased. CONCLUSION: Before versus after
      the rule change, hydrocodone prescriptions decreased and oxycodone and tramadol
      prescriptions increased. Milligram morphine equivalents prescribed varied
      considerably across and within classes of procedures, but the schedule change did
      not affect mean milligram morphine equivalents prescribed for most procedures.

PMID- 30093276
TI  - Superusers: Drivers of health care resource utilization in the national trauma
      population.
AB  - BACKGROUND: Health care spending is driven by a very small percentage of
      Americans, many of whom are patients with prolonged durations of stay. The
      objective of this study was to characterize superusers in the trauma population.
      METHODS: The National Trauma Data Bank for 2008-2012 was queried. Superusers were
      defined as those with a duration of stay in the top 0.06% of the population and
      were compared with the remainder of the population to determine differences in
      demographic characteristics, comorbidities, prehospital factors, and outcomes.
      Multivariate analysis was used to determine independent predictors of being
      classified as a superuser. RESULTS: A total of 3,617,261 patients met inclusion
      criteria, with 34,728 qualifying as superusers. Mean duration of stay for
      superusers was 58.7 days compared with the average 4.6 days (P < .001).
      Superusers were more likely to be male, black, Medicaid insured, and have a
      higher Injury Severity Score and lower Glasgow Coma Scale score. The hospital
      course of superusers was likely to be complicated by pneumonia, acute respiratory
      distress syndrome, decubitus ulcer, and acute kidney injury. CONCLUSION: Age,
      sex, race, and insurance were associated with prolonged use of inpatient care in
      the trauma patient population. Specific comorbidities and complications are
      associated with being a superuser. This subset of the trauma population confers a
      disproportionate burden on the health care system and can serve as a potential
      target for intervention.

PMID- 30093277
TI  - Comparison between robotic and open pancreaticoduodenectomy with modified
      Blumgart pancreaticojejunostomy: A propensity score-matched study.
AB  - BACKGROUND: This study is to clarify the feasibility of robotic
      pancreaticoduodenectomy in terms of surgical risks, clinically relevant
      postoperative pancreatic fistula, and oncologic outcomes compared with open
      pancreaticoduodenectomy by using propensity score matching. Traditional open
      pancreaticoduodenectomy and robotic pancreaticoduodenectomy have been compared
      only in small, retrospective, and nonrandomized cohort studies with variable
      quality. METHODS: Prospectively collected data for pancreaticoduodenectomy were
      evaluated. Comparison between robotic pancreaticoduodenectomy and open
      pancreaticoduodenectomy was carried out after propensity-score matching. A total
      of 117 robotic pancreaticoduodenectomy and 128 open pancreaticoduodenectomy cases
      were performed during the study period. After propensity score matching, 87 cases
      were included for comparison in each cohort. RESULTS: Longer operation time, less
      blood loss, more lymph nodes harvested, and less delayed gastric emptying were
      noted in the robotic pancreaticoduodenectomy cases. We found no significant
      difference regarding the overall postoperative complications by Clavien-Dindo
      classification, postpancreatectomy hemorrhage, wound infection rate, and
      postoperative hospital stay. Clinically relevant postoperative pancreatic fistula
      was not significantly different between robotic pancreaticoduodenectomy and open
      pancreaticoduodenectomy, regardless of the Callery risk factor, with overall
      clinically relevant postoperative pancreatic fistula of 8.0% by robotic
      pancreaticoduodenectomy and 12.6% by open pancreaticoduodenectomy after
      propensity score matching. We found no survival difference between robotic
      pancreaticoduodenectomy and open pancreaticoduodenectomy when the comparison was
      specifically performed for each primary periampullary malignancy. CONCLUSION:
      Robotic pancreaticoduodenectomy is associated with less blood loss, less delayed
      gastric emptying, and more lymph node yield. Propensity scored-matched analysis
      revealed that robotic pancreaticoduodenectomy is not inferior to open
      pancreaticoduodenectomy in terms of clinically relevant postoperative pancreatic
      fistula, surgical risks, and survival outcomes.

PMID- 30093279
TI  - Impact of anticipated financial burden on patient decision to undergo
      contralateral prophylactic mastectomy.
AB  - BACKGROUND: We sought to determine whether patients undergoing contralateral,
      prophylactic mastectomy have greater anticipated and actual costs and financial
      burden than patients undergoing unilateral mastectomy, whether these financial
      considerations influence surgical decision making, and whether this affects
      satisfaction with surgical decision and overall quality of life. METHODS: Female
      patients with unilateral breast cancer who underwent mastectomy at a large
      academic institution were surveyed regarding their financial experience
      surrounding the decision whether to undergo contralateral, prophylactic
      mastectomy. RESULTS: Of 109 patients approached, 101 completed the survey
      (response rate: 93%); 55 patients (55%) had contralateral, prophylactic
      mastectomy. Of the respondents, 16% reported that their decision was at least
      somewhat affected by anticipated costs. More patients opting for contralateral,
      prophylactic mastectomy had a "very large" anticipated financial burden than
      unilateral mastectomy patients (26% vs 9%, P = .037), but actual out-of-pocket
      costs and financial burden were similar between the two groups. Contralateral,
      prophylactic mastectomy patients, however, did not differ from unilateral
      mastectomy patients in their satisfaction with their decision nor quality of
      life, regardless of out-of-pocket costs or financial burden (P > .05).
      CONCLUSION: Although contralateral, prophylactic mastectomy patients are more
      likely to anticipate a "very large" financial burden compared with unilateral
      mastectomy patients, this does not seem to deter them from the contralateral
      procedure.

PMID- 30093278
TI  - Same day discharge after thyroidectomy is safe and effective.
AB  - : Historically, thyroidectomies have been performed as inpatient operations due
      to concerns of postoperative bleeding and symptomatic hypocalcemia. We aim to
      demonstrate that outpatient thyroidectomy can be performed safely. METHODS: This
      report outlines a 7-year retrospective analysis (2009-2016) of outpatient vs
      inpatient thyroidectomies, with outcomes including hematoma, blood loss,
      recurrent laryngeal nerve injury, symptomatic hypocalcemia, and postoperative
      emergency room (ER) visits. RESULTS: A total of 1460 thyroidectomies were
      performed: 1272 (87%) outpatient and 188 (13%) inpatient. Five outpatients: 4
      total thyroidectomies (TT), 1 TT with a central lymph node dissection (CLND), and
      1 partial thyroidectomy (PT) developed postoperative hematomas (0.34%) at post
      discharge hour 3, 9, 10, 13, and 42. Average time to discharge was 2 hours and 37
      minutes. Hematomas were evacuated successfully in the operating room under local
      anesthesia with a 2-day average hospital stay. There were no differences between
      TT, thyroid lobectomy (TL), and PT procedures for postoperative hematoma
      (p=0.17). Outpatient compared to inpatient thyroidectomy was more likely to have
      been performed in patients with lower American Society of Anesthesia scores (2.3
      vs 2.9, p<0.0001), less mean blood loss (74 vs 227 ml, p<0.0001), lesser age (52
      vs 56 years, p=0.0012), less extensive dissection (p<0.0001), and fewer RLN
      injuries (2.4% vs 8.5%, p<0.0001). There was no difference between outpatient and
      inpatient symptomatic hypocalcemia (6.3% vs 9.6%, p=0.09), 30-day postoperative
      ER visits (8.8% vs 9.6%, p=0.73), and postoperative hematoma (0.39% vs 0%,
      p=0.39). There was one inpatient mortality from stroke. CONCLUSION: Postoperative
      hematomas can be managed safely without life-threatening complications suggesting
      outpatient thyroidectomy can be performed safely by an experienced surgeon, and
      adverse sequelae dealt with in a safe and effective manner.

PMID- 30093280
TI  - 75 years of the Central Surgical Association: The last quarter century.

PMID- 30093281
TI  - Sex hormones and insulin sensitivity in adolescent girls with type 1 diabetes.

PMID- 30093282
TI  - Time Alone for Adolescents With Their Providers During Clinical Encounters: It Is
      Not That Simple!

PMID- 30093283
TI  - Improving Outcomes in Chronic Myeloid Leukemia Over Time in the Era of Tyrosine
      Kinase Inhibitors.
AB  - Most patients with chronic myeloid leukemia (CML) receiving treatment with BCR
      ABL1 tyrosine kinase inhibitors (TKIs) will achieve favorable responses.
      Moreover, TKI therapy enables patients to experience long-term survival, with
      survival rates similar to those of individuals without CML. This enhanced
      survival has resulted from the availability of multiple BCR-ABL1 TKIs with
      efficacy, not only in frontline treatment, but, importantly, also in second- and
      third-line treatment. We have reviewed the changes in long-term outcomes in the
      era of TKI therapy and how these changes have affected treatment practices. We
      discuss the development of imatinib, the first BCR-ABL1 TKI, followed by newer
      TKIs, including nilotinib, dasatinib, bosutinib, and ponatinib. We consider the
      key studies that led to their development as frontline or later-line therapies,
      their safety profiles, and their effect on improving patient outcomes. With these
      improved outcomes, the definition of an optimal response has become more
      stringent, and treatment monitoring strategies have changed. Second-line patient
      populations have evolved from those with resistance to, or intolerance of,
      imatinib to those with moderate responses to, or low-grade adverse events with,
      imatinib. Although all TKIs are associated with high survival rates, newer TKIs
      have been associated with lower disease progression rates and, importantly,
      deeper treatment responses and, potentially, a greater chance of future treatment
      free remission. Finally, we consider the unmet needs of patients with CML,
      including the challenges remaining for those without optimal responses during TKI
      therapy and new therapies and strategies to identify such patients at diagnosis.

PMID- 30093284
TI  - Early neurological deterioration in acute ischemic stroke: A propensity score
      analysis.
AB  - BACKGROUND: To investigate whether endovascular therapy (EVT) was one of the
      factors influencing the incidence of early neurological deterioration (END) in
      patients with acute ischemic stroke (AIS) as compared with intravenous
      thrombolysis alone. METHODS: This study was based on our single-center's database
      that included information on stroke patients hospitalised between January 2012
      and September 2015. A total of 220 patients who underwent EVT after IV rt-PA, EVT
      or IV rt-PA alone. To reduce the lack of randomization, we conducted a propensity
      score analysis using the SPSS custom dialog. After matching was completed, the 2
      groups (with END versus non-END) were compared between matched groups. Variables
      with a p value <= 0.1 by univariate analysis were candidates for inclusion in
      logistic regression analysis. RESULTS: Of 220 acute ischemic strokes attended,
      213 patients were included (62.0%, 23.0% and 15.0% with circulation occlusion in
      the anterior, posterior and both branches, respectively). END was detected in 68
      patients (31.9%). Multivariable analysis showed that END was positively
      associated with glucose level (OR, 1.40; 95%CI, 1.10-1.79; p = 0.007), uric acid
      level (OR, 1.01; 95% CI, 1.00-1.02; p = 0.026) and treatment methods (EVT: OR,
      3.87; 95% CI, 1.32-11.35; p = 0.014). However, there was significant difference
      in baseline data (NIHSS and INR) between EVT group and non-EVT group. CONCLUSION:
      Our findings suggest that hyperglycemia, hyperuricemia and EVT may be
      independently associated with END in AIS, even after controlling for possible
      confound factors. Further studies are warranted to confirm these results.

PMID- 30093285
TI  - Ginger (zingiber officinale) might improve female fertility: A rat model.
AB  - BACKGROUND: Ginger (Zingiber officinale) is a well known and extensively used
      antioxidant in traditional remedies. In this study, we aimed to investigate the
      effects of ginger powder on ovarian folliculogenesis and implantation in rats.
      METHODS: There were two study groups. In the 5-day treatment group (one estrous
      cycle), 100 mg ginger powder, 200 mg ginger powder or distilled water was given
      for 5 days to the three subgroups each containing seven rats. In the 10-day
      treatment group, same doses were given for 10 days (two estrous cycle) to the
      three subgroups each containing seven rats. At the end of the 5th and 10th days,
      ovarian volumes, ovarian weights, primordial follicles, antral follicles, atretic
      follicles, and corpus luteum counts were assessed. To evaluate the angiogenic
      effects of ginger, vascular endothelial growth factor (VEGF) and for the
      antioxidant effects of ginger endothelial nitric oxide synthase (eNOS) were
      examined in the ovaries and in the endometrium immunohistochemically. RESULTS: In
      the 5-day treatment group, antral follicle count and ovarian stromal VEGF were
      significantly high in the 100 mg ginger subgroup in comparison to the control
      group (p < 0.05). In the 10-day treatment group, endometrial VEGF and ovarian
      stromal eNOS were significantly high in the 100 mg ginger subgroup in comparison
      to the control group (p < 0.05). There was no statistically significant
      difference at 200 mg ginger dose both in 5-day and 10-day treatment groups.
      CONCLUSION: The increases in the antral follicle count and ovarian stromal VEGF
      in the 100 mg/5-day treatment subgroup indicate that ginger have positive effects
      on folliculogenesis in short term with low dose. Additionally, ginger may enhance
      implantation in rats in long term with low dose.

PMID- 30093286
TI  - Human acellular dermis increases surgical site infection and overall complication
      profile when compared with submuscular breast reconstruction: An updated meta
      analysis incorporating new products?.
AB  - BACKGROUND: Human acellular dermal matrix (HADM) is an increasingly used adjunct
      to breast reconstruction. Previous meta-analyses demonstrate increased risks of
      complications, but these studies largely represent one product. The purpose of
      this study is to stratify outcomes on the basis of a meta-analysis of
      complications incorporating all new studies after 2012 and their associated new
      human-based products. METHODS: A query of the MEDLINE database for articles on
      HADM and breast reconstruction from January 2012 to October 2015 yielded 172
      citations. Two levels of screening identified 47 relevant studies. Thirteen
      studies were used in comparative meta-analysis. RESULTS: Complication rates were
      higher in HADM patients: total complications, 17.7% versus 6.1%; seroma, 8.3%
      versus 5.4%; infection, 7.2% versus 5.9%; and flap necrosis, 14.7% versus 7.1%.
      Meta-analysis revealed a statistically significant increased risk of total
      complications in patients who underwent reconstruction with HADM when compared
      with their submuscular reconstruction cohort (p = 0.03; relative risk (RR) =
      1.46; confidence interval (CI): 1.04-2.04). Patients who underwent reconstruction
      with HADM demonstrated a significantly increased risk of flap necrosis (p < 0.01;
      RR = 2.39; CI: 1.8-3.16) and infection (p = 0.02; RR = 1.5; CI: 1.07-2.09) when
      compared with those who underwent submuscular reconstruction. There was no
      significant difference in seroma, hematoma, or implant explantation between these
      two groups. CONCLUSIONS: This study suggests an increased risk of overall
      complications, specifically infection and flap necrosis, in patients who
      underwent tissue expander/implant breast reconstruction with HADM when compared
      with those who underwent submuscular placement. This must be weighed against the
      advantages in enhancing aesthetic outcomes, increasing intraoperative fill
      volume, and ameliorating capsular contracture.

PMID- 30093287
TI  - Response to: Time course of improvement after re-repair procedure for VPI
      management.

PMID- 30093288
TI  - Modulation of motor learning by a paired associative stimulation protocol
      inducing LTD-like effects.
AB  - BACKGROUND: Paired associative stimulation (PAS) induces long-term potentiation
      (LTP)-like effects when interstimulus intervals (ISIs) between electrical
      peripheral nerve stimulation and transcranial magnetic stimulation (TMS) to M1
      are approximately 21-25 ms (PASLTP). It was previously reported that two forms of
      motor learning (i.e., mode-free and model-based learning) can be differentially
      modulated by PASLTP depending on the different synaptic inputs to corticospinal
      neurons (CSNs), which relate to posterior-to-anterior (PA) or anterior-to
      posterior (AP) currents induced by TMS (PA or AP inputs, respectively). However,
      the effects of long-term depression (LTD)-inducing PAS with an ISI of
      approximately 10 ms (PASLTD) on motor learning and its dependency on current
      direction have not yet been tested. OBJECTIVE: To investigate whether, and how,
      PASLTD affects distinct types of motor learning. METHODS: Eighteen healthy
      volunteers participated. We adopted the standard PAS using suprathreshold TMS
      with the target muscle relaxed, as well as subthreshold PAS during voluntary
      contraction, which was suggested to selectively recruit PA or AP inputs depending
      on the orientation of the TMS coil. We examined the effects of suprathreshold and
      subthreshold PASLTD on the performance of model-free and model-based learning, as
      well as the corticospinal excitability, indexed as the amplitudes of motor evoked
      potentials (MEPs). RESULTS: PASLTD inhibited model-free learning and MEPs only
      when subthreshold AP currents were applied. The PASLTD protocols tested here
      showed no effects on model-based learning. CONCLUSIONS: PASLTD affected model
      free learning, presumably by modulating CSN excitability changes, rather than PA
      inputs, which are thought to be related to model-free learning.

PMID- 30093289
TI  - Inactivated influenza vaccine effectiveness and an analysis of repeated
      vaccination for children during the 2016/17 season.
AB  - OBJECTIVES: We assessed the vaccine effectiveness (VE) of inactivated influenza
      vaccine (IIV) in children 6 months to 15 years of age during the 2016/17 season.
      In addition, we estimated the impact of repeated vaccination in children on VE.
      METHODS: Our study for VEs in preventing influenza and admission due to influenza
      were conducted according to a test-negative case-control design (TNCC) based on
      influenza rapid diagnostic test results. We also analyzed the VE by vaccine
      status in the current and previous seasons for the impact of repeated
      vaccination. RESULTS: During the 2016/17 season, the quadrivalent IIV was used in
      Japan. The adjusted VE in preventing influenza illness was 38% (95% CI, 29-46)
      against influenza A and 39% (95% CI, 18-54) against influenza B. Infants showed
      no significant VE. The VE in preventing hospitalization was not demonstrated. For
      the analysis of repeated vaccination, the vaccine was effective only when
      immunization occurred in the current season. The children who were immunized in
      two consecutive seasons were more likely to develop influenza compared to those
      immunized in the current season only (odds ratio, 1.58 [95% CI, 1.05-2.38],
      adjusted odds ratio, 1.53 [95% CI, 0.99-2.35]). However, the odds ratio of
      repeated vaccination was not significant when the analysis excluded those who
      developed influenza in the previous season. CONCLUSIONS: VE in children in the
      2016/17 season was similar to values previously reported. Repeated vaccination
      interfered with the VE against any influenza infection in the 2016/17 season. The
      results of our study suggest that decreased VE by repeat vaccination phenomenon
      was associated with immunity by influenza infection in the previous season.
      However, the influenza vaccine should be recommended every season for children.

PMID- 30093290
TI  - Revisiting assumptions about age-based mixing representations in mathematical
      models of sexually transmitted infections.
AB  - BACKGROUND: Sexual mixing between heterogeneous population subgroups is an
      integral component of mathematical models of sexually transmitted infections
      (STIs). This study compares the fit of different mixing representations to survey
      data and the impact of different mixing assumptions on the predicted benefits of
      hypothetical human papillomavirus (HPV) vaccine strategies. METHODS: We compared
      novel empirical (data-driven) age mixing structures with the more commonly-used
      assortative-proportionate (A-P) mixing structure. The A-P mixing structure
      assumes that a proportion of sexual contacts - known as the assortativity
      constant, typically estimated from survey data or calibrated - occur exclusively
      within one's own age group and the remainder mixes proportionately among all age
      groups. The empirical age mixing structure was estimated from the National Survey
      on Sexual Attitudes and Lifestyles 3 (Natsal-3) using regression methods, and the
      assortativity constant was estimated from Natsal-3 as well. Using a simplified
      HPV transmission model under each mixing assumption, we calibrated the model to
      British HPV16 prevalence data, then estimated the reduction in steady-state
      prevalence and the number of infections averted due to expanding HPV vaccination
      from 12- through 26-year-old females alone to 12-year-old males or 27- to 39-year
      old females. RESULTS: Empirical mixing provided a better fit to the Natsal-3 data
      than the best-fitting A-P structure. Using the model with empirical mixing as a
      reference, the model using the A-P structure often under- or over-estimated the
      benefits of vaccination, in one case overestimating by 2-fold the number of
      infections prevented due to extended female catch-up in a high vaccine uptake
      setting. CONCLUSIONS: An empirical mixing structure more accurately represents
      sexual mixing survey data, and using the less accurate, yet commonly-used A-P
      structure has a notable effect on estimates of HPV vaccination benefits. This
      underscores the need for mixing structures that are less dependent on unverified
      assumptions and are directly informed by sexual behavior data.

PMID- 30093292
TI  - Percutaneous coronary intervention of chronic total occlusions: When and how to
      treat.
AB  - : Chronic coronary total occlusions (CTO) are diagnosed in up to 20% of patients
      with coronary artery disease and have a detrimental effect on patients' quality
      of life and long-term prognosis. The exponential developments in CTO percutaneous
      coronary intervention (PCI) equipment, recanalization techniques, and operator
      expertise have been merged into the hybrid approach that represents a
      percutaneous revascularization algorithm for treating CTOs and has led to
      technical success over 90% at experienced centers. Therefore, patient selection
      for CTO PCI should be focused on anticipated patient benefit in terms of health
      status and long-term prognosis rather than coronary anatomic complexity. TABLE OF
      CONTENTS: This review will provide an overview of the clinical presentation and
      characteristics of patients with a CTO and will discuss the essential needs
      toward judicious patient selection for percutaneous CTO revascularization
      according to contemporary knowledge. Furthermore, the current high standard
      revascularization techniques in dedicated CTO PCI will be discussed.

PMID- 30093291
TI  - De novo assembly and analysis of midgut transcriptome of the argasid tick
      Ornithodoros erraticus and identification of genes differentially expressed after
      blood feeding.
AB  - Ticks are hematophagous vectors of great medical and veterinary importance
      because they transmit numerous pathogenic microorganisms to humans and animals.
      The argasid Ornithodoros erraticus is the main vector of tick-borne human
      relapsing fever and African swine fever in the Mediterranean Basin. Tick
      enterocytes express bioactive molecules that perform key functions in blood
      digestion, feeding, toxic waste processing and pathogen transmission. To explore
      new strategies for tick control, in this work we have obtained and compared the
      midgut transcriptomes of O. erraticus female ticks before and after a blood meal
      and identified the genes whose expression is differentially regulated after
      feeding. The transcript sequences were annotated, functionally and structurally
      characterised and their expression levels compared between both physiological
      conditions (unfed females and fed females at 2 days post-engorgement). Up to
      29,025 transcripts were assembled, and 9290 of them corresponded to
      differentially expressed genes (DEGs) after feeding. Of these, 4656 genes were
      upregulated and nearly the same number of genes was downregulated in fed females
      compared to unfed females. BLASTN and BLASTX analyses of the 29,025 transcripts
      allowed the annotation of 9072 transcripts/proteins. Among them, the most
      numerous were those with catalytic and binding activities and those involved in
      diverse metabolic pathways and cellular processes. The analyses of functional
      groups of upregulated DEGs potentially related to the digestion of proteins,
      carbohydrates and lipids, and the genes involved in the defence response and
      response to oxidative stress, confirm that these processes are narrowly regulated
      in ticks, highlighting their complexity and importance in tick biology. The
      expression patterns of six genes throughout the blood digestion period revealed
      significant differences between these patterns, strongly suggesting that the
      transcriptome composition is highly dynamic and subjected to important variation
      along the trophogonic cycle. This may guide future studies aimed at improving the
      understanding of the molecular physiology of tick digestion and digestion-related
      processes. The current work provides a more robust and comprehensive
      understanding of the argasid tick digestive system.

PMID- 30093293
TI  - Vitamin D status correlates with the markers of cystic fibrosis-related pulmonary
      disease.
AB  - BACKGROUND: The prevalence of Vitamin D deficiency remains high in cystic
      fibrosis despite daily supplementation. Vitamin D as an immunomodulator has been
      related to lower respiratory tract infections in children. The present study was
      undertaken to examine the association between vitamin D status and markers of
      cystic fibrosis-related pulmonary disease including exacerbations, bacterial
      colonization and pulmonary function. METHODS: The study includes review of
      records of 51 cystic fibrosis patients. Baseline patient variables and serum
      vitamin D levels were recorded. Based on vitamin D levels study patients were
      divided into three groups: vitamin-D sufficient (>=20 ng/mL), vitamin-D
      insufficient (12 to 20 ng/mL), and vitamin D-deficient (<=12 ng/ml). RESULTS: The
      proportion of children with deficient, insufficient and sufficient vitamin D
      levels were 47.1%, 15.7%, and 37.2%, respectively. Female sex, bacterial
      colonization and a greater number of exacerbations were associated with highest
      odds of developing vitamin D deficiency in patients with CF with 1.77 (0.22-4.61)
      (p = 0.002), 2.9(0.57-14.82) (p = 0.011), and 5.12 (1.28-20.50) (p = 0.021)
      respectively. The comparison of vitamin-D levels taken during exacerbations,
      colonization and during routine follow-up were significant [16.04 (7.42-27.91),
      24.3 (15.5-32.4) and 48.54 (18.37-78.7) ng/ml, p < 0.001]. The FEV1 was
      determined in 24 patients; the comparison was significant between vitamin D
      deficient and -sufficient groups [0.75 (0.717-0.777) vs. 0.82 (0.74-0.92) p <
      0.05]. CONCLUSION: We concluded that vitamin D deficiency was highly prevalent in
      children with CF, despite daily supplementation of the vitamin in diet. Further,
      vitamin D deficiency was associated with a higher rate of pulmonary exacerbations
      and higher incidence of pulmonary bacterial colonization. In addition, in younger
      patients, low vitamin D levels were associated with reduced pulmonary function.

PMID- 30093294
TI  - High impact of seasonal temperature changes on acclimation of photoprotection and
      radiation-induced damage in field grown Arabidopsis thaliana.
AB  - At temperate latitudes environmental factors such as irradiance, including
      ultraviolet-B radiation (UV-B, 280-315 nm), temperature and day length vary
      widely over the course of a year in a concerted way. In the present study
      physiological acclimation of photoprotection, growth and development of the model
      organism Arabidopsis thaliana were correlated to these strongly but gradually
      changing conditions in a one year field study. Plants were sown in the field
      avoiding any manipulation (and abrupt change) during their life. Developmental
      rate was strongly dependent on prevailing temperature. Moderate signs of light
      stress in form of photoinhibition at photosystem II were significantly related to
      solar irradiances while amount of DNA damage was low and not correlated to UV-B
      irradiance. Although all the markers were hypothesized to primarily react to
      radiation, multiple regression analysis showed at least a similarly strong
      influence of temperature as that of light. Especially for the classical UV
      screening compounds a positive correlation to UV-B radiation during the course of
      the year was absent, whereas there was a significant negative correlation between
      temperature and quercetin content. The sum of violaxanthin cycle pigments was
      correlated to both, irradiance and temperature, but with opposite sign. Epidermal
      UV-B transmittance was also much better related to air temperature than to UV-B
      irradiance. The data show that under natural conditions temperature has at least
      a similar importance for photoprotective acclimation and partially also for
      photosensitivity as solar irradiance.

PMID- 30093295
TI  - Evaluation of 4-phenylamino-substituted naphthalene-1,2-diones as tubulin
      polymerization inhibitors.
AB  - A series of 4-phenylamino-substituted naphthalene-1,2-dione derivatives were
      prepared and evaluated as effective antiproliferative agents. MTT assays showed
      that the compounds with a methyl group on the nitrogen linker exhibited potent
      antiproliferative activities against human cancer cells. The mechanistic study
      revealed that these compounds could induce mitochondrial depolarization, which
      resulted in intracellular ROS production, and they also acted as tubulin
      polymerization inhibitors. Moreover, the typical compound could arrest A549 cells
      in the G2/M phase, resulting in cellular apoptosis and induced mitotic arrest in
      A549 cells through disrupting microtubule dynamics.

PMID- 30093296
TI  - Synthesis and biological activity investigation of azole and quinone hybridized
      phosphonates.
AB  - Phosphonates, azoles and quinones are pharmacophores found in bioactive
      compounds. A series of phosphonates conjugated to azoles and quinones with
      variable carbon chain lengths were synthesized in 3-4 steps with good yield.
      Antifungal assay of these compounds showed that ethyl protected phosphates have
      excellent inhibitory activity against phytopathogenic fungus Fusarium
      graminearum, and the free-base phosphates have good activity against human
      pathogenic fungi Aspergillus flavus and Candida albicans. Structure- activity
      relationship (SAR) studies showed activity increases with longer carbon chain
      length between phosphonate and anthraquinone analogs consisting of azole and
      quinone moieties. These newly synthesized compounds also have mild antibacterial
      activities to Gram positive bacteria, including methicillin-resistant
      Staphylococcus aureus (MRSA). Cytotoxicity analysis of these compounds against
      HeLa cells reveals that the phosphoric acid analogs are less toxic compared to
      ethyl protected phosphonates. Three leads compounds have been identified with
      prominent antifungal activity and low cytotoxicity.

PMID- 30093297
TI  - Establishing Therapeutic Equivalence of Complex Pharmaceuticals: The Case of
      Dabigatran.
AB  - Dabigatran is widely used for stroke prevention in atrial fibrillation.
      Dabigatran is no longer patent-protected in Canada and 2 generic formulations
      were recently approved by Health Canada. Branded dabigatran uses a complex
      formulation to maintain the acidic microenvironment required for maximal
      absorption. Consequently, food does not influence its bioavailability and the
      efficacy and safety of dabigatran are similar with or without concomitant intake
      of proton pump inhibitors (PPIs). Unfortunately, current bioequivalence criteria
      do not mandate testing of the generic formulations with food or with concomitant
      intake of PPIs; thus, the only data available for the approved generic products
      are in fasted, healthy volunteers. Without confirmation that the bioavailability
      of the generic dabigatran products is maintained in the presence of food or with
      coadministration of PPIs, it is uncertain whether they will afford patients the
      same protection from stroke as the branded product. Clinicians and patients must
      be made aware of this limitation to make informed prescribing decisions. The
      rules for establishing bioequivalence have not kept pace with the increasing
      complexity of pharmaceutical products; we urge regulators to update the
      regulatory process to ensure the therapeutic equivalence of generic products.

PMID- 30093298
TI  - The Risk of Subsequent Atrial Fibrillation in Patients With Atrial Flutter: The
      Role of Conduction Abnormalities Reflected on the Surface Electrocardiogram.

PMID- 30093299
TI  - Difference Between Persistent Aneurysm, Regressed Aneurysm, and Coronary Dilation
      in Kawasaki Disease: An Optical Coherence Tomography Study.
AB  - BACKGROUND: Coronary artery (CA) aneurysms are a serious complication of Kawasaki
      disease (KD). Conventional imaging techniques often described segments with
      regressed aneurysms as normal, whereas studies have shown significant endothelial
      dysfunction. METHODS: KD patients with aneurysms scheduled for routine coronary
      angiography underwent optical coherence tomography (OCT) imaging between 2013 and
      2016. Microstructural coronary changes were compared between normal CA segments
      and those with dilation, regressed aneurysms, and persistent aneurysms. RESULTS:
      OCT was performed on 33 patients aged 12.0 +/- 5.4 years, 8.5 +/- 5.4 years after
      KD diagnosis. Of the 79 segments analyzed, 25 had persistent aneurysms, 22
      regressed aneurysms, 11 CA dilation, and 21 no CA involvement. Intimal thickness
      was 489 +/- 173 MUm, 304 +/- 158 MUm, 102 +/- 68 MUm, and 63 +/- 29 MUm,
      respectively (P < 0.001). There was a linear correlation between the maximum
      aneurysm size and the intimal thickness, as well as coronary dimension at the
      time of OCT. Fibrosis (54 segments, 68%) and cellular infiltration (22 segments,
      28%) were found more often in segments with CA involvement, but also those
      without (P = 0.01; P = 0.02). Destruction of the media (34 segments, 43%),
      calcifications (6 segments, 8%), neovascularization (18 segments, 23%), and white
      thrombi (8 segments, 10%) were found almost exclusively in segments with a
      history of aneurysms. CONCLUSIONS: Intimal hyperplasia, fibrosis, and cellular
      infiltration were found in all categories of CA involvement, whereas
      calcification, destruction of the media, neovascularization, and white thrombi
      were found essentially only in segments with saccular or fusiform aneurysms.
      Prospective studies with outcome correlations are needed to see if this is
      associated with an increased risk of late adverse events.

PMID- 30093301
TI  - The Cardiovascular Burden of Undiagnosed Familial Hypercholesterolemia: Need to
      Modify Guidelines to Encourage Earlier Diagnosis and Therapy.

PMID- 30093300
TI  - Simplified Canadian Definition for Familial Hypercholesterolemia.
AB  - Familial hypercholesterolemia (FH) is an autosomal codominant lipoprotein
      disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C)
      and high risk of premature atherosclerotic cardiovascular disease. Definitions
      for FH rely on complex algorithms that are on the basis of levels of total or LDL
      C, clinical features, family history, and DNA analysis that are often difficult
      to obtain. We propose a novel simplified definition for FH. Definite FH includes:
      (1) elevated LDL-C (>= 8.50 mmol/L); or (2) LDL-C >= 5.0 mmol/L (for age 40 years
      or older; >= 4.0 mmol/L if age younger than 18 years; and >= 4.5 mmol/L if age is
      between 18 and 39 years) when associated with at least 1 of: (1) tendon
      xanthomas; or (2) causal DNA mutation in the LDLR, APOB, or PCSK9 genes in the
      proband or first-degree relative. Probable FH is defined as subjects with an
      elevated LDL-C (>= 5.0 mmol/L) and the presence of premature atherosclerotic
      cardiovascular disease in the patient or a first-degree relative or an elevated
      LDL-C in a first-degree relative. LDL-C cut points were determined from a large
      database comprising > 3.3 million subjects. To compare the proposed definition
      with currently used algorithms (ie, the Simon Broome Register and Dutch Lipid
      Clinic Network), we performed concordance analyses in 5987 individuals from
      Canada. The new FH definition showed very good agreement compared with the Simon
      Broome Register and Dutch Lipid Clinic Network criteria (kappa = 0.969 and 0.966,
      respectively). In conclusion, the proposed FH definition has diagnostic
      performance comparable to existing criteria, but adapted to the Canadian
      population, and will facilitate the diagnosis of FH patients.

PMID- 30093302
TI  - The Emerging Role of Palliative Care in the Management of Canadians With Heart
      Failure.

PMID- 30093303
TI  - The 'scent' and 'flavour' of hypertension.

PMID- 30093304
TI  - Appropriateness in prescribing PPIs: A position paper of the Italian Society of
      Gastroenterology (SIGE) - Study section "Digestive Diseases in Primary Care".
AB  - The introduction of proton pump inhibitors (PPIs) into clinical practice about
      thirty years ago has greatly improved our therapeutic approach to acid-related
      diseases for their well-recognized efficacy and safety. Despite the well-defined
      indications, however, the use of PPIs continues to grow every year in both
      western and eastern countries and this phenomenon poses serious queries that
      include the onset of potential adverse effects and the increase in health care
      costs. The major reason explaining this worrying market expansion is the
      inappropriate use of PPIs. In order to re-establish a correct use of these
      effective drugs in daily clinical practice, the Italian Society of
      Gastroenterology (SIGE), nominated a panel of experts who reviewed the available
      clinical literature and produced a series of updated position statements on the
      use of PPIs in clinical practice.

PMID- 30093305
TI  - Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage
      in a Mouse Stroke Model.
AB  - Synaptic NMDA receptors activating nuclear calcium-driven adaptogenomics control
      a potent body-own neuroprotective mechanism, referred to as acquired
      neuroprotection. Viral vector-mediated gene transfer in conjunction with
      stereotactic surgery has previously demonstrated the proficiency of several
      nuclear calcium-regulated genes to protect in vivo against brain damage caused by
      toxic extrasynaptic NMDA receptor signaling following seizures or stroke. Here we
      used noninvasive nose-to-brain administration of Activin A and SerpinB2, two
      secreted nuclear calcium-regulated neuroprotectants, for post-injury treatment of
      brain damage following middle cerebral artery occlusion (MCAO) in C57BL/6N mice.
      The observed reduction of the infarct volume was comparable to the protection
      obtained by intracerebroventricular injection of recombinant Activin A or
      SerpinB2 or by stereotactic delivery 3 weeks prior to the injury of a recombinant
      adeno-associated virus containing an expression cassette for the potent
      neuroprotective transcription factor Npas4. These results establish post-injury,
      nose-to-brain delivery of Activin A and SerpinB2 as effective and possibly
      clinically applicable treatments of acute and chronic neurodegenerative
      conditions.

PMID- 30093308
TI  - Gastro-gastric fistula after gastric bypass.

PMID- 30093309
TI  - Antibiotic dispensing practice in Sri Lankan community pharmacies: A simulated
      client study.
AB  - BACKGROUND: Dispensing antibiotics without a prescription, although forbidden by
      Sri Lankan law since 1986, is a common practice throughout the country. This
      study attempted to quantify this practice for the first time. OBJECTIVES: To
      evaluate the response of community pharmacy staff to an antibiotic product
      request without a prescription and to explore possible factors influencing such
      practice. METHODS: A cross-sectional simulated client study was conducted from
      Jan to Sept 2017. A total of 242 community pharmacies were visited by trained
      simulated clients (SCs) and they requested for one of four antibiotics
      (erythromycin tablets, amoxicillin syrup, metronidazole tablets, or ciprofloxacin
      tablets) without a prescription. Data on the interaction between the pharmacy
      staff and SC was recorded using a data collection sheet immediately after each
      visit. RESULTS: Nearly 50% of pharmacies had a pharmacist on duty during the
      visit. Attending pharmacy staff asked for a prescription for the requested
      antibiotic in 47% of the instances. Only 16 (7%) pharmacy staff recommended the
      SC to see a doctor. Overall, 61% of pharmacies dispensed antibiotics without a
      prescription. The highest dispensed antibiotic was ciprofloxacin (44/63 requests;
      70%) and the least was amoxicillin (32/62; 52%). Patient history was obtained in
      only a few instances and none of the pharmacies dispensed alternative over the
      counter medicines. The availability of a pharmacist reduced the risk of
      dispensing an antibiotic without a prescription (Adj. OR = 0.54, 95% CI: 0.30
      0.95; P = 0.033), however, it did not have any impact on patient history taking.
      CONCLUSIONS: Dispensing antibiotics without a prescription is a common practice
      in Sri Lankan community pharmacies. In most instances, pharmacy staff neither
      inquired about patient history nor requested the patient to obtain the advice of
      a doctor. Presence of a pharmacist may reduce dispensing antibiotics without
      prescription, but may not have an effect on interactions with clients requesting
      antibiotics.

PMID- 30093307
TI  - Berberine Reduces Pyruvate-driven Hepatic Glucose Production by Limiting
      Mitochondrial Import of Pyruvate through Mitochondrial Pyruvate Carrier 1.
AB  - BACKGROUND: Mitochondrial pyruvate import via mitochondrial pyruvate carrier
      (MPC) is a central step in hepatic gluconeogenesis. Berberine inhibits hepatic
      gluconeogenesis, but the mechanism is incompletely understood. This study aims to
      investigate whether berberine could reduce excessive hepatic glucose production
      (HGP) by limiting mitochondrial import of pyruvate through MPC1. METHODS: High
      fat diet (HFD) feeding augmented HGP. The effects of berberine on hepatic fatty
      acid oxidation, sirtuin3 (SIRT3) induction and mitochondrial pyruvate carrier 1
      (MPC1) function were examined. FINDINGS: HFD feeding increased hepatic acetyl
      coenzyme A (acetyl CoA) accumulation with impaired pyruvate dehydrogenase (PDH)
      activity and increased pyruvate carboxylase (PC) induction. Berberine reduced
      acetyl CoA accumulation by limiting fatty acid oxidation and prevented
      mitochondrial pyruvate shift from oxidation to gluconeogenesis through
      carboxylation. Upon pyruvate response, SIRT3 binded to MPC1 and stabilized MPC1
      protein via deacetylation modification, facilitating mitochondrial import of
      pyruvate. Berberine preserved the acetylation of MPC1 by suppression of SIRT3
      induction and impaired MPC1 protein stabilization via protein degradation,
      resultantly limiting mitochondrial pyruvate supply for gluconeogenesis.
      INTERPRETATION: Berberine reduced acetyl CoA contents by limiting fatty acid
      oxidation and increased MPC1 degradation via preserving acetylation, thereby
      restraining HGP by blocking mitochondrial import of pyruvate. These findings
      suggest that limitation of mitochondrial pyruvate import might be a therapeutic
      strategy to prevent excessive hepatic glucose production.

PMID- 30093306
TI  - Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy.
AB  - Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by dystrophin
      gene mutation. Conceptually, replacing the mutated gene with a normal one would
      cure the disease. However, this task has encountered significant challenges due
      to the enormous size of the gene and the distribution of muscle throughout the
      body. The former creates a hurdle for viral vector packaging and the latter begs
      for whole-body therapy. To address these obstacles, investigators have invented
      the highly abbreviated micro-dystrophin gene and developed body-wide systemic
      gene transfer with adeno-associated virus (AAV). Numerous microgene
      configurations and various AAV serotypes have been explored in animal models in
      many laboratories. Preclinical data suggests that intravascular AAV micro
      dystrophin delivery can significantly ameliorate muscle pathology, enhance muscle
      force, and attenuate dystrophic cardiomyopathy in animals. Against this backdrop,
      several clinical trials have been initiated to test the safety and tolerability
      of this promising therapy in DMD patients. While these trials are not powered to
      reach a conclusion on clinical efficacy, findings will inform the field on the
      prospects of body-wide DMD therapy with a synthetic micro-dystrophin AAV vector.
      This review discusses the history, current status, and future directions of
      systemic AAV micro-dystrophin therapy.

PMID- 30093311
TI  - 10-year follow-up after laparoscopic sleeve gastrectomy: Outcomes in a
      monocentric series.
AB  - BACKGROUND: Sleeve gastrectomy (SG) has grown into the most popular bariatric
      operation. Nevertheless, a scarcity of long-term outcomes are available.
      OBJECTIVES: This study aims at evaluating the long-term percent weight loss
      (%WL), excess weight loss (%EWL), weight regain (WR), and co-morbidity resolution
      rates in a single-center cohort undergoing SG as a primary procedure, with a
      minimum 10-year follow-up. SETTING: University hospital, Italy. METHODS: One
      hundred eighty-two morbidly obese patients with body mass index (BMI) 46.6 +/-
      7.3 kg/m2 underwent SG. Obesity-related co-morbidities (type 2 diabetes,
      hypertension, sleep apnea, gastroesophageal reflux disease) were investigated.
      Predictors of dichotomous dependent-variable diabetes remission were computed
      using a binomial logistic regression. RESULTS: Patient retention rate was 77%.
      Mean %WL was 30.9, %EWL was 52.5%, and WR (>=25% maximum WL) occurred in 10.4%.
      Baseline BMI significantly (P = .001) and linearly predicted %EWL (10 yr %EWL =
      18.951 + initial BMI * .74); the super-obese subgroup generated substantially
      greater WL compared with those with BMI <50 kg/m2 (%EWL 48.0 +/- 18.5 versus 61.5
      +/- 23.2; P < .001). Type 2 diabetes remission occurred in 64.7%; 42.9% patients
      developed de novo gastroesophageal reflux disease symptoms postoperatively (P <
      .0001). CONCLUSIONS: SG generates sustained WL and co-morbidity resolution up to
      10 years postoperatively. Although a notable portion of patients experience WR,
      mean %WL persists to exceed 30%, translating in adequate WL also in the long
      term. Additionally, WR does not seem to impact negatively on co-morbidity
      resolution. SG represents a safe and effective bariatric operation, which easily
      grants the possibility to proceed to revisional bariatric surgery in patients
      with WR or failure to WL.

PMID- 30093313
TI  - Approximating Bayesian Inference through Model Simulation.
AB  - The ultimate test of the validity of a cognitive theory is its ability to predict
      patterns of empirical data. Cognitive models formalize this test by making
      specific processing assumptions that yield mathematical predictions, and the
      mathematics allow the models to be fitted to data. As the field of cognitive
      science has grown to address increasingly complex problems, so too has the
      complexity of models increased. Some models have become so complex that the
      mathematics detailing their predictions are intractable, meaning that the model
      can only be simulated. Recently, new Bayesian techniques have made it possible to
      fit these simulation-based models to data. These techniques have even allowed
      simulation-based models to transition into neuroscience, where tests of cognitive
      theories can be biologically substantiated.

PMID- 30093310
TI  - A comparison of rodent models of vertical sleeve gastrectomy.
AB  - BACKGROUND: Although vertical sleeve gastrectomy (VSG) is fashioned in humans by
      applying multiple staple loads, rodent VSG is generally created through a single
      staple load application. OBJECTIVES: To investigate the impact of a 2-staple load
      VSG rat model more closely resembling the multistaple load operation done in
      humans on weight, metabolic outcomes, and the microbiome and how these compare
      with those obtained with the standard one-staple load model. SETTING: University
      research facility, United States. METHODS: High-fat diet-induced obese male rats
      were randomized to single-staple load VSG (VSG1), 2-staple load VSG (VSG2), or
      sham operation (Sham). Outcomes included weight and composition, food intake,
      glucose metabolism, lipids, bile acids, and intestinal microbiome. Statistical
      comparisons were performed using analysis of variance. RESULTS: Both procedures
      resulted in substantial weight and body fat loss compared with Sham-treated
      animals. Weight loss was modestly greater for VSG2 compared with VSG1. Food
      intake was reduced in both procedures and accounted for the observed weight
      reduction. Glucose tolerance and plasma and hepatic lipid profiles were improved
      comparably in VSG1 and VSG2 relative to Sham. Bile acids were higher for VSG2
      compared with Sham but not significantly different between VSG1 and VSG2. Neither
      procedure impacted intestinal microbiome richness and diversity compared with
      Sham across multiple intestinal sections. Colonic Actinobacteria was more
      abundant in VSG2 than in Sham. Relative abundances of bacterial phyla did not
      differ among VSG1, VSG2, and Sham across the remaining intestinal sections.
      CONCLUSIONS: Although VSG1 or VSG2 offer effective and overall comparable
      platforms for the study of obesity, VSG2 resulted in superior weight loss.

PMID- 30093312
TI  - [Hodgkin lymphoma and target definition guidelines].
AB  - Treatment for stage I and II Hodgkin lymphoma is based on a combination of
      chemotherapy and radiotherapy, with a high successful cure rate. Now, the aim is
      to decrease toxicity rates. Positron-emission tomography scan is recommended as
      pretreatment baseline and is very useful to define precisely target volumes for
      planning radiation therapy. Based on these changes were developed guidelines for
      modern radiation therapy called involved node and " involved site ".

PMID- 30093314
TI  - Morning Blood Pressure Surge Relates to Autonomic Neural Activity in Young Non
      Dipping Adults: The African-PREDICT Study.
AB  - BACKGROUND: It is well established that an exaggerated morning blood pressure
      surge (MBPS) is associated with an increased risk for cardiovascular disease
      development in hypertensive individuals. However, in non-dipping individuals, a
      lower surge was reportedly associated with increased cardiovascular risk.
      Sympathetic nervous system activity is involved in 24-hour blood pressure
      fluctuations, including night-time dipping and the MBPS. To better understand
      this interaction, we investigated associations of MBPS with heart-rate
      variability and baroreceptor sensitivity in young healthy dippers and non
      dippers. METHODS: We included black and white men and women (n=827), aged 20-30
      years and determined the MBPS using two formulas: the sleep-trough and dynamic
      morning surge. For autonomic function we determined baroreceptor sensitivity and
      heart-rate variability. RESULTS: The majority of non-dippers in this population
      were black (70.4%), presenting lower sleep-trough and dynamic morning surge (all
      p<0.001). Heart-rate variability was comparable between dippers and non-dippers,
      whereas baroreceptor sensitivity was higher in non-dippers (p=0.021). Despite a
      suppressed MBPS profile in non-dippers, we found both sleep-trough (beta=-0.25;
      p=0.039) and dynamic morning surge (beta=-0.14; p=0.047) to be inversely and
      independently associated with 24-hour heart-rate variability (total power). These
      results were absent in dippers. CONCLUSIONS: In conclusion, we found a higher
      night-time blood pressure coupled with lower MBPS in young healthy non-dippers.
      Furthermore, this lower MBPS was independently and negatively associated with
      autonomic neural activity, suggesting increased autonomic function involvement in
      MBPS suppression of non-dippers. The predictive value of suppressed nocturnal
      dipping pattern should be investigated while taking autonomic neural activity
      into account.

PMID- 30093315
TI  - Appropriate surgical margin for odontogenic myxoma: a review of 12 cases.
AB  - OBJECTIVE: Odontogenic myxoma (OM) is a rare benign tumor that is frequently
      nonencapsulated and invades the surrounding bone, resulting in a high risk of
      recurrence. However, the optimal surgical technique and appropriate surgical
      margin remains controversial. Here, we report our clinical investigation of 12
      patients with OM diagnosed histopathologically. STUDY DESIGN: We retrospectively
      reviewed the records of 12 patients treated at our institution. Osteotomy or bone
      shaving with enucleation was generally performed with 5-mm bony margins from the
      radiologic extent of the tumor. RESULTS: One half of the cases occurred in the
      maxilla and the other half in the mandible. Treatment for maxillary OM was
      enucleation in 2 patients and maxillectomy in 4 patients. Treatment for
      mandibular OM was enucleation with shaving of the surrounding bone in 1 patient
      and segmental mandibulectomy in 5 patients. Radiographs of surgical specimen
      removed by segmental mandibulectomy indicated that the mean distance between the
      tumor and the margin was 5.4 (range 3.4-7.0) mm. Tumor recurrence was noted in 1
      patient who had undergone enucleation alone. CONCLUSION: The 1-cm surgical margin
      for OM, as reported conventionally, might not be necessary. A prospective study
      is needed to determine the appropriate surgical margin for OM.

PMID- 30093316
TI  - Oral lichenoid reactions may possibly be associated with abatacept: A case report
      and literature update.
AB  - Oral lichenoid reactions (OLRs) comprise a group of conditions with a common
      clinical appearance and histopathologic pattern that may be induced by several
      conditions or medications. This report describes an OLR possibly induced by a
      biologic agent. A 69-year-old woman with rheumatoid arthritis presented with a
      chief complaint of oral pain. The patient retroactively reported of skin lesions
      as well. Clinically, she had mixed red-white mucosal lesions and ulcers
      suggestive of an OLR. This diagnosis was supported by histopathologic findings.
      Withholding the putative etiologic agent, abatacept, resulted in immediate
      alleviation of both oral and skin lesions. Abatacept and other biologics are
      thought to help treat inflammation and are becoming more commonly prescribed to
      treat rheumatoid arthritis. However, the clinicians should explore these
      medications as a causative factor for OLR.

PMID- 30093317
TI  - Bifid variations of the mandibular canal: cone beam computed tomography
      evaluation of 1000 Northern Chinese patients.
AB  - OBJECTIVES: The aim of this study was to evaluate and quantify variations of
      bifid mandibular canals (BMCs) in a population of Northern China by using cone
      beam computed tomography (CBCT). STUDY DESIGN: CBCT images of 1000 consecutive
      patients were analyzed by using the NewTom proprietary software. BMCs were
      identified and classified on the basis of the Naitoh classification. Linear and
      angular measurements of BMCs were performed. Statistical analyses were conducted
      by using chi2 and Wilcoxon tests. RESULTS: BMCs were observed in 13.2% of 1000
      patients and 8.4% of 2000 sides. The prevalence of BMCs was significantly lower
      in patients in the first 2 decades and in cases with a class II molar
      relationship. The retromolar canal (68.4%) was the most common type of BMC
      observed. No buccolingual canals were identified; however, 2 special canals were
      detected. A classification system of 3 subtypes of retromolar canals was
      suggested. On average, the beginning site of the branches from the opening of the
      main canal was at a distance of 8.1 mm. The mean diameter and length of BMCs were
      2.1 mm and 12.6 mm, respectively. CONCLUSIONS: This study underlined the
      prevalence and characteristics of BMCs in a population of Northern China.
      Preoperative identification of BMCs with CBCT may help prevent postoperative
      complications.

PMID- 30093318
TI  - Comparison of different methods to calculate venous admixture in anaesthetized
      horses.
AB  - OBJECTIVE: The aim of this study was to compare different methods to determine
      venous admixture (Qs/Qt) in anaesthetized horses. The first objective was to
      estimate Qs/Qt using jugular venous blood oxygen content (Qs/Qtjugular), and a
      fixed value for the oxygen extraction (F-shunt). The second objective was to
      assess the influence of blood pressure and positioning on oxygen extraction. The
      third objective was to perform regression analysis between jugular and mixed
      venous blood oxygen tensions. STUDY DESIGN: Prospective, experimental trial.
      ANIMALS: The study was performed with seven warmblood horses that were
      anaesthetized with detomidine, butorphanol, ketamine, diazepam and isoflurane in
      oxygen. METHODS: Multiple simultaneous arterial, jugular venous and pulmonary
      arterial blood samples were taken under normotensive and hypotensive conditions
      in lateral and dorsal recumbency. Arterial, mixed venous, and end-capillary
      oxygen content were calculated. RESULTS: A significant correlation between Qs/Qt
      and Qs/Qtjugular was found [intraclass correlation coefficient (ICC) = 0.68, p <
      0.001], and Bland-Altman analysis showed a bias of -11.5% and wide limits of
      agreement (-27.7% to 4.6%). F-shunt significantly correlated with Qs/Qt (ICC =
      0.88, p < 0.001), and Bland-Altman analysis showed a lower bias (-1.97) and
      narrower limits of agreement (-13.8% to 9.9%). Positioning and blood pressure
      significantly influenced oxygen extraction. The regression formula was Y = 0.80X
      + 2.61 (where Y is the calculated mixed venous oxygen tension and X is the
      jugular venous oxygen tension) when outliers were excluded (ICC=0.82, p < 0.001).
      CONCLUSIONS AND CLINICAL RELEVANCE: This study shows that F-shunt provides
      reasonable estimates of Qs/Qt but can possibly be improved by using simple
      algorithms without the need for pulmonary arterial catheterization. These
      algorithms use blood pressure- and positioning-dependent oxygen extraction and
      regression analysis between jugular venous and pulmonary arterial oxygen tension.
      Although promising, the validity of these algorithms needs to be determined in
      future studies.

PMID- 30093319
TI  - An alveolar recruitment maneuver followed by positive end-expiratory pressure
      improves lung function in healthy dogs undergoing laparoscopy.
AB  - OBJECTIVE: To evaluate the effects of an alveolar recruitment maneuver (ARM)
      followed by 5 cmH2O positive end-expiratory pressure (PEEP) in dogs undergoing
      laparoscopy. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: A
      group of 20 dogs undergoing laparoscopic ovariectomy. METHODS: Dogs were sedated
      with acepromazine and methadone intramuscularly; anesthesia was induced with
      propofol intravenously and maintained with inhaled isoflurane. The following
      baseline ventilatory setting (BVS) was administered: tidal volume of 12 mL kg-1,
      inspiratory to expiratory ratio of 1:2, inspiratory pause 25% of inspiratory
      time, no PEEP and a respiratory rate to maintain end-tidal carbon dioxide tension
      between 5.3 and 7.3 kPa. Then, 10 minutes after the pneumoperitoneum, 10 dogs
      (RM) underwent a sustained inflation ARM followed by BVS plus 5 cmH2O PEEP, while
      10 dogs (NO-RM) were left with BVS throughout the procedure. Gas exchange and
      respiratory system mechanics were evaluated before the pneumoperitoneum (PPpre),
      before ARM (PP10), 30 minutes later (PP30) and 20 minutes after pneumoperitoneum
      discontinuation (PPpost20). Data were analyzed using anova (p < 0.05). RESULTS:
      The Fshunt at PP30 and PPpost20 was lower (p < 0.001) in the RM (2.3 +/- 2.2 and
      4.7 +/- 3.7%) than in the NO-RM (5.2 +/- 2.1 and 11.1 +/- 5.2%), and PaO2 at PP30
      and PPpost20 was higher (p < 0.001) in the RM (67.3 +/- 4.2 and 60.1 +/- 9.4 kPa)
      than in the NO-RM (50.2 +/- 7.4 and 45.5 +/- 11.1 kPa). Static compliance of the
      respiratory system at PP30 and PPpost20 was greater (p < 0.001) in the RM (2.4 +/
      0.2 and 2.1 +/- 0.4 mL cmH2O-1 kg-1) than in the NO-RM (0.9 +/- 0.4 and 1.2 +/-
      0.2 mL cmH2O-1 kg-1). CONCLUSIONS AND CLINICAL RELEVANCE: In dogs undergoing
      laparoscopy, ARM followed by 5 cmH2O PEEP improves gas exchange and respiratory
      system mechanics.

PMID- 30093320
TI  - Description of a regional anaesthesia technique for the dorsal cranium in the
      dog: a cadaveric study.
AB  - OBJECTIVE: To identify landmarks and to describe a technique for nerve blockade
      of the dorsal cranium in dogs. STUDY DESIGN: Anatomic cadaveric study. ANIMALS: A
      total of 39 dog cadavers, weighing 18.0 +/- 9.7 kg (mean +/- standard deviation).
      METHODS: The study was performed in three parts. In the initial part, cadavers
      were dissected to determine the location of the frontal, zygomaticotemporal, and
      major occipital nerves, and to identify prominent landmarks for their blockade.
      In the second part, one technique was developed to block each of the frontal and
      zygomaticotemporal nerves, and two techniques, rostral and caudal, were developed
      to block the major occipital nerve. Injection solution was 0.05% methylene blue
      in 0.5% bupivacaine. In the third part, cadavers were used to test the techniques
      developed in the second part with 0.04 mL kg-1 of the same injectate administered
      at each site (maximal volume 0.5 mL per site). The length of nerve stained was
      measured, with a length >=6 mm considered successful. Confidence intervals were
      calculated using Fisher's exact test. RESULTS: Success rates (95% confidence
      interval) for the frontal, zygomaticotemporal, and rostral and caudal locations
      for the major occipital nerve were 94% (80-99%), 91% (76-98%), 74% (58-86%) and
      77% (59-89%), respectively. With a combination of both locations, the success
      rate for the major occipital nerve was 100% (90-100%). CONCLUSION AND CLINICAL
      RELEVANCE: This study describes a simple regional anaesthesia technique using
      palpable anatomical landmarks that may provide analgesia for dogs undergoing
      craniotomy.

PMID- 30093321
TI  - Young adults' adjustment to a recent diagnosis of multiple sclerosis: The role of
      identity satisfaction and self-efficacy.
AB  - BACKGROUND: Although multiple sclerosis (MS) is often diagnosed during young
      adulthood (18-30 years), there is a lack of knowledge on the psychological
      adjustment to the illness among recently diagnosed young adult patients.
      OBJECTIVE/HYPOTHESIS: The aims of the study were to describe the adjustment to MS
      (depression, positive and negative affect) in a group of young adult patients and
      to investigate the role of identity satisfaction and self-efficacy in MS on
      adjustment. We hypothesized that the relationship between identity satisfaction
      and adjustment was mediated by self-efficacy (goal setting and symptom
      management). METHODS: The cross-sectional study involved 66 patients (63.6%
      women) with a mean age of 25.2 years (SD = 3.4) who had been diagnosed for no
      more than three years. Patients completed measures of identity satisfaction
      (Identity Motives Scale), Self-efficacy in MS (SEMS), Depression (CESD-10),
      Positive and Negative Affect (PANAS). Data were analyzed through factorial ANOVAs
      and hierarchical regression analysis. RESULTS: Thirty-eight percent of patients
      reported depressive symptoms and negative affect mean score was higher than in
      the general population. Higher identity satisfaction was directly related to
      lower depression. Self-efficacy in goal setting partially mediated the
      relationship between identity satisfaction and positive affect, whereas self
      efficacy in symptom management totally mediated the effect of identity
      satisfaction on negative affect. All results were significant at p < 0.05.
      CONCLUSIONS: The results suggest the usefulness of addressing identity
      redefinition and self-efficacy in psychological interventions aimed at promoting
      young adults' adjustment to MS in an early phase of the illness.

PMID- 30093322
TI  - [Real-world effectiveness of ivacaftor in children with cystic fibrosis and the
      G551D mutation].
AB  - INTRODUCTION: Ivacaftor is a cystic fibrosis transmembrane conductance regulator
      (CFTR) potentiator that has been shown to improve the nutritional status and lung
      function of cystic fibrosis patients with the G551D mutation in clinical trials.
      The objective of this study was to describe the real-world progress of children
      receiving ivacaftor. METHODS: We describe the real-world progress of four
      children with cystic fibrosis and the F508del/G551D genotype comparing data
      during ivacaftor treatment with baseline and with the year before commencing
      treatment. RESULTS: Our sample comprised 4 children aged between 6 and 14 years
      and including one with a recent diagnosis of CF and other with persistent
      Mycobacterium abscessus (M. abscessus) and recurrent allergic bronchopulmonary
      aspergillosis. The baseline FEV1 was 58.5% to 81.8% of the predicted value, and
      ivacaftor was taken for a mean 24 months (range, 12-30 months). All patients
      experienced a significant and sustained improvement in lung function. Compared to
      baseline, the weight z-score improved by 1.53 points, and the BMI z-score by 1.6
      points. Compared to the year before starting ivacaftor, the frequency of
      Pseudomonas aeruginosa (P. aeruginosa) isolates decreased (-0.4/patient/year), as
      did the number of respiratory exacerbations (-1.8/patient/year). The weight
      adjusted dose of lipase per kilogram decreased progressively in all patients. In
      1 patient, a previously persistent M. abscessus infection and recurrent allergic
      bronchopulmonary aspergillosis resolved during treatment. CONCLUSIONS: Children
      with cystic fibrosis and the F508del/G551D genotype receiving treatment with
      ivacaftor experienced a real-world improvement in lung function, nutritional
      status, respiratory exacerbations, isolation of P. aeruginosa, and dose of
      pancreatic enzymes.

PMID- 30093323
TI  - Pericytes reduce inflammation and collagen deposition in acute wounds.
AB  - BACKGROUND: Pericytes have been shown to have mesenchymal stromal cell-like
      properties and play a role in tissue regeneration. The goal of this study was to
      determine whether the addition of a pericyte sheet to a full-thickness dermal
      wound would enhance the healing of an acute wound. METHODS: Human muscle-derived
      pericytes and human dermal fibroblasts were formed into cell sheets, then applied
      to full-thickness excisional wounds on the dorsum of nu/nu mice. Histology was
      performed to evaluate epidermal and dermal reformation, inflammation and
      fibrosis. In addition, real-time reverse transcriptase-polymerase chain reaction
      (RT-PCR) was used to determine cytokine response. RESULTS: Pericytes were
      detected in the wounds until day 16 but not fibroblasts. Decrease in wound size
      was noted in pericyte sheet-treated wounds. Enhanced neo-vascularization and
      healthy granulation tissue formation were noted in the pericyte-treated wounds.
      Expression of type I collagen messenger RNA (mRNA) was significantly higher in
      the fibroblast-treated group, whereas Type III collagen mRNA showed significant
      increase in the pericyte group at days 3, 6 and 9 compared with the fibroblast
      and no-cell groups. Trichrome staining revealed thick unorganized collagen
      fibrils in the fibroblast-treated wounds, whereas pericyte-treated wounds
      contained thinner and more alligned collagen fibrils. Tumor necrosis factor (TNF)
      alpha mRNA levels were increased in the fibroblast-treated wounds compared with
      pericyte-treated wounds. DISCUSSION: The addition of pericytes may confer
      beneficial effects to wound healing resulting in reduced recruitment of
      inflammatory cells and collagen I deposition, potential to enhance wound closure
      and better collagen alignment promoting stronger tissue.

PMID- 30093324
TI  - In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal
      cells delivering membrane-bound tumor necrosis factor-related apoptosis inducing
      ligand in osteosarcoma pre-clinical models.
AB  - BACKGROUND: Osteosarcoma (OS) is the most frequent pediatric malignant bone
      tumor. OS patients have not seen any major therapeutic progress in the last 30
      years, in particular in the case of metastatic disease, which requires new
      therapeutic strategies. The pro-apoptotic cytokine Tumor necrosis factor (TNF)
      Related Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while
      sparing normal cells, making it a promising therapeutic tool in several types of
      cancer. However, many OS cell lines appear resistant to recombinant human
      (rh)TRAIL-induced apoptosis. We, therefore, hypothesized that TRAIL presentation
      at the membrane level of carrier cells might overcome this resistance and trigger
      apoptosis. METHODS: To address this, human adipose mesenchymal stromal cells
      (MSCs) transfected in a stable manner to express membrane-bound full-length human
      TRAIL (mbTRAIL) were co-cultured with several human OS cell lines. RESULTS: This
      induced apoptosis by cell-to-cell contact even in cell lines initially resistant
      to rhTRAIL. In contrast, mbTRAIL delivered by MSCs was not able to counteract
      tumor progression in this OS orthotopic model. DISCUSSION: This was partly due to
      the fact that MSCs showed a potential to support tumor development. Moreover, the
      expression of mbTRAIL did not show caspase activation in adjacent tumor cells.

PMID- 30093325
TI  - Cord blood-derived cytokine-induced killer cells combined with blinatumomab as a
      therapeutic strategy for CD19+ tumors.
AB  - BACKGROUND: Cytokine-induced killer cells (CIKs) are an advanced therapeutic
      medicinal product (ATMP) that has shown therapeutic activity in clinical trials
      but needs optimization. We developed a novel strategy using CIKs from banked
      cryopreserved cord blood units (CBUs) combined with bispecific antibody (BsAb)
      blinatumomab to treat CD19+ malignancies. METHODS: CB-CIKs were expanded in vitro
      and fully characterized in comparison with peripheral blood (PB)-derived CIKs.
      RESULTS: CB-CIKs, like PB-CIKs, were mostly CD3+ T cells with mean 45% CD3+CD56+
      and expressing mostly TCR(T cell receptor)alphabeta with a TH1 phenotype. CB-CIK
      cultures had, however, a larger proportion of CD4+ cells, mostly CD56-, as well
      as a greater proportion of naive CCR7+CD45RA+ and a lower percentage of effector
      memory cells, compared with PB-CIKs. CB-CIKs were very similar to PB-CIKs in
      their expression of a large panel of co-stimulatory and inhibitory/exhaustion
      markers, except for higher CD28 expression among CD8+ cells. Like PB-CIKs, CB
      CIKs were highly cytotoxic in vitro against natural killer (NK) cell targets and
      efficiently lysed CD19+ tumor cells in the presence of blinatumomab, with 30-60%
      lysis of target cells at very low effector:target ratios. Finally, both CB-CIKs
      and PB-CIKs, combined with blinatumomab, showed significant therapeutic activity
      in an aggressive PDX Ph+ CD19+ acute lymphoblastic leukemia model in NOD-SCID
      mice, without sign of toxicity or graft-versus-host disease. The improved
      expansion protocol was finally validated in good manufacturing practice
      conditions, showing reproducible expansion of CIKs from cryopreserved cord blood
      units with a median of 28.8 * 106 CIK/kg. DISCUSSION: We conclude that CB-CIKs,
      combined with bispecific T-cell-engaging antibodies, offer a novel, effective
      treatment strategy for leukemia.

PMID- 30093326
TI  - Functional impairment of MSC induced by transient warming events: Correlation
      with loss of adhesion and altered cell size.
AB  - BACKGROUND: We recently showed that transient warming effects decreased the
      functional and adhesion properties of mesenchymal stromal cells (MSC) while post
      thaw viability remained high. In an attempt to better predict functional
      impairment of cryopreserved MSC, we further analysed the correlation between
      viability, immunosuppressive activity and adhesion of cells exposed or not to
      warming events. METHODS: MSC prepared from six umbilical cords were frozen to 
      130 degrees C and immediately transferred in a dry ice container or exposed to
      room temperature for 2 to 10 min (warming events) prior to storage in liquid
      nitrogen. Viability, functionality (inhibition of T-cell proliferation), adhesion
      and expression of various integrins were evaluated. RESULTS: The monotonic loss
      of functional activity with time was proportional to the length of warming events
      to which MSC were subjected and correlated with the monotonic loss of adhesion
      capacity. In contrast, post-thaw viability assessment did not predict functional
      impairment. Interestingly, flow cytometry analyses revealed the emergence of a
      FSClow population present in the viable cell fraction of freshly thawed MSC,
      which displayed poor adhesion capacity and expressed low levels of integrin
      beta5. The prevalence of this FSClow population increased with the length of
      warming events and correlated with impaired functional and adhesion properties.
      DISCUSSION: Our results reveal that loss of functional activity (4-day test)
      induced by transient warming events could be predicted by evaluating adhesion (2
      hr test) or FSC profile (10-min test) of MSC immediately post-thaw. These
      observations could lead to the development of surrogate tests for rapidly
      assessing the functional quality of cryopreserved MSC.

PMID- 30093327
TI  - Patient Perspectives of Surgical Residents' Communication: Do Skills Improve Over
      Time With a Communication Curriculum?
AB  - OBJECTIVE: We aimed to assess surgical residents' communication confidence and
      skills, analyze resident feedback on our ongoing communication curriculum, and
      report feedback-driven updates. DESIGN: Surgical residents care for patients in
      the clinic and hospital and participate in a communication curriculum. We measure
      patient perception of resident communication using the Communication Assessment
      Tool (CAT). We assess resident skills confidence and collect curriculum feedback
      after each quarterly session. SETTING: 900-bed tertiary care hospital with
      surgical residency program and simulation center. PARTICIPANTS: General surgery
      residents (PGY 1-5). RESULTS: We collected 353 CAT forms from patients in the
      clinic and hospital on 27 residents. Overall percent "excellent" scores (primary
      outcome) was 84%. In multivariate analysis we found a statistically significant
      increase in individuals' CAT scores over time at a rate of 1% improvement per
      month (p = 0.02). We observed significant improvement of skill confidence in 9
      out of 10 training modules. Resident perception of the curriculum has improved
      over time with 90% of learners rating the course "A" or "A+" across all years. We
      updated the curriculum to be more learner-centered by: 1) providing differential
      scenarios for learner level; 2) engaging chief residents as co-faculty; 3) using
      both professional and volunteer (former patient) actors as SPs; and 4) refining
      the flow and timing of module practice. CONCLUSIONS: We assessed and analyzed
      surgical residents' communication skills and confidence over 17 months; both
      showed significant increase over the course of the communication curriculum. We
      adapted our curriculum using resident feedback and engagement. Our results
      suggest that communication training can be an effective tool to improve non
      technical skills.

PMID- 30093328
TI  - The FES Test: Are We Ready?
AB  - PURPOSE: The FES hands-on skills test is administered using a $100,000 computer
      based simulator. Few of our trainees have practiced on this device. Our aim was
      to evaluate our GS residents' baseline endoscopic skills and eventually develop a
      simulation-based endoscopy curriculum and clarify performance-based assessment
      criteria. METHODS: General surgery residents' colonoscopy skills were assessed
      using a computer-based endoscopy simulator (CBES) during their biannual
      simulation-based OSCE-type assessments. Trainees were asked to reach the ileum in
      <5 minutes with minimal patient pain and complications. Module 1 (easy) was
      assigned to PGY 1-4 residents and module 5 (hard) to both PGY 4s and 5s. The
      colonoscope insertion length, % time with no pain, % time in "red out", and
      complications were recorded. Performance grading criteria were driven by
      literature review and expert opinion. Residents were assessed in the fall 2017;
      they were then given scoring criteria, a step-by-step instruction manual, and a
      voluntary hands-on session with the CBES. Residents repeated the same assessment
      in the spring 2018. RESULTS: 30 PGY-1s, 12 PGY-2s, 8 PGY-3s, 9 PGY-4s and 7 PGY
      5s GS residents participated in the fall colonoscopy assessment. In module 1, 66%
      of PGY-4s, 50% of PGY-3s, 8% of PGY-2s and 0% of the PGY-1s intubated the ileum
      (p<0.05). In module 5, 30% of PGY 5 and 22% of PGY 4 residents completed the task
      (p<0.05). 15 PGY-1s, 5 PGY-2s, 1 PGY-3, 2 PGY-4s, and 1 PGY-5 participated in the
      voluntary hands-on session. All residents completing the fall assessment
      undertook the same task in the spring. In module 1, 89% of PGY-4s, 100% of the
      PGY-3s, 75% of PGY-2s and 70% of the PGY-1s completed the task. In module 5, 30%
      of PGY 5 and 34 % of PGY 4 residents completed the task. Residents who
      participated in the voluntary hands-on session (n= 24, 96% task completion)
      outperformed residents (n= 42, 64% task completion) that did not participate
      (p<0.05). CONCLUSIONS: Most of our GS residents could not initially intubate the
      ileum using the CBES. Prior experience with the CBES was the only factor strongly
      correlated with successful task completion. A voluntary hands-on teaching session
      allowed 96% of participating trainees to subsequently achieve CBES task
      completion. Developing a formal simulation-based curriculum suggests we can
      better prepare surgical trainees for the FES exam.

PMID- 30093329
TI  - Time Out of General Surgery Specialty training in the UK: A National Database
      Study.
AB  - OBJECTIVE: General surgery specialty training in the United Kingdom takes 6 years
      and allows trainees to take time out of training. Studies from the United States
      have highlighted an increasing trend for taking time out of surgical training for
      research. This study aimed to evaluate trends in time out of training and the
      impact on the duration of UK general surgical specialty training. DESIGN,
      SETTING, AND PARTICIPANTS: A cohort study using routinely collected surgical
      training data from the Intercollegiate Surgical Curriculum Program database for
      General surgery trainees registered from August 1, 2007. Trainees were classified
      as Completed Training or In-Training. Out of training periods were identified and
      time in training calculated (both unadjusted and adjusted for out of training
      periods) with a predicted time in training for those In-Training. RESULTS: Of the
      trainees still In-Training (n = 994), a greater proportion had taken time out of
      training compared with those who had completed training (n = 360; 54.5% vs 45.9%,
      p < 0.01). A greater proportion of the In-Training group had undertaken a formal
      research period compared with the Completed Training group (35.1% vs 6.1%, p <
      0.01). Total unadjusted training time in the Completed Training group was a
      median 6.0 (interquartile range 6.0-7.0) years compared with a predicted
      unadjusted training time in the In-Training group, with an out of training period
      recorded, of a median 8.0 (interquartile range 7.0-9.0) years. CONCLUSIONS:
      Trainees are increasingly taking time out of surgical training, particularly for
      research, with a subsequent increase in total time of training. This should be
      considered when redesigning surgical training programs and planning the future
      surgical workforce.

PMID- 30093330
TI  - Efficacy of Medical Student Surgery Journal Club.
AB  - BACKGROUND: Journal clubs exist in a variety of forms in medical schools across
      the United States. Many incorporate a full spectrum of medical specialties, some
      are specific to certain interest groups or specialties, and many widely vary in
      whether or not they are school mandated or student-run. While these clubs are
      ubiquitously scattered throughout medical education, there has been very little
      quantitative or qualitative analysis regarding the efficacy of these clubs in
      enhancing medical students' abilities to evaluate clinical literature. The
      purpose of this study was to evaluate the effects of attending Surgical Journal
      Club meetings at Eastern Virginia Medical School from both a qualitative and
      quantitative perspective. The authors' hypothesis was that regular attendance of
      these sessions would improve student performance from a multitude of perspectives
      and demonstrate the value of clinical literature analysis earlier in medical
      education. METHODS: A fifteen question Likert survey was administered on an
      optional basis to thirty-six medical students attending journal club. Responses
      were analyzed anonymously, and there was no incentive or demerit for completing
      the survey. Data was compiled and the mean, median, and mode for each question
      calculated with "5" corresponding to "Strongly Agree" and "1" corresponding to
      "Strongly Disagree." RESULTS: Twenty-seven of thirty-six attendees to our seventh
      journal club meeting completed the survey. Student responses were overwhelming
      positive, with all but one question reaching above "Agree" by analysis of the
      mean responses. CONCLUSION: Journal clubs remain an integral part of medical
      education but their importance has been diminished in recent years due to the
      increasing demands of other aspects of the first two years in medical school. We
      described a medical student run/established journal club that increased students'
      interest in surgery, their perceived knowledge-base, and comfort in critically
      analyzing medical journal articles.

PMID- 30093332
TI  - Global Health in the 21st Century: Equity in Surgical Training Partnerships.
AB  - INTRODUCTION: Safe and affordable surgical care has been recognized as an
      important component of global health. One of the challenges in providing safe and
      affordable surgical care is the shortage of trained surgical workforce.
      Partnerships have developed between institutions in high-income countries (HICs)
      and low- and middle-income countries (LMICs) to strengthen and expand surgical
      education in LMICs. As these relationships evolve, emphasis needs to focus on
      development of equitable, bilateral partnerships. METHODS: We reviewed different
      global surgery education partnerships to describe key components and features of
      successful partnerships. We then provide a framework for equitable global
      surgical training partnerships. RESULTS: Key features of equitable global
      surgical education partnerships included an alignment with local priorities, long
      term collaborations, and locally integrated, competency-based training. To
      develop a partnership, both parties must meet and perform a needs assessment of
      the LMIC institution and jointly agree how the partnership can best address these
      needs. Both the HIC and LMIC institutions must clearly define their goals and
      expectations. Ideally, a set of output measures will be defined to assess the
      success of the partnership. CONCLUSIONS: Improving surgical education in LMIC
      countries is an integral part of health equity in global surgery. Key components
      of equitable education partnerships focus on local ownership and long-term
      relationships. Each party needs to clearly define goals and expectations for the
      partnership. Equity is essential and unequal relationships must be avoided.

PMID- 30093331
TI  - Fellow Perceptions of Residency Training in Obstetrics and Gynecology.
AB  - OBJECTIVE: To evaluate the perceptions of current and former fellows in
      obstetrics and gynecology (OBG) subspecialties of their readiness for fellowship
      training. METHODS: A previously used survey was modified and distributed in 2016
      to current and former fellows in gynecologic oncology, maternal-fetal medicine,
      reproductive endocrinology-infertility, and female pelvic medicine and
      reconstructive surgery. The survey explored domains of professionalism,
      independent practice, psychomotor ability, clinical evaluation, and scholarship.
      A standard Likert scale was employed and domains/responses were tailored to each
      subspecialty. Standard statistical models were utilized. RESULTS: A total of 478
      fellows responded to the survey. Nearly 75% of fellows from each specialty
      reported feeling prepared or very prepared for fellowship. More than 65% of
      fellows from each specialty reported feeling very prepared to perform core
      surgical procedures. More than 90% of respondents reported having opportunities
      during residency to independently develop a plan of action for patients on labor
      and delivery. Fewer respondents reported opportunities to independently manage
      postoperative complications-40.7% of gynecologic oncology and 44.7% of female
      pelvic medicine and reconstructive surgery reported having such opportunities,
      whereas 91.9% of maternal-fetal medicine respondents reported having had such
      opportunities. While 46.4% of respondents received education on scientific
      writing during residency, 80% reported writing a manuscript as a resident.
      CONCLUSIONS: The majority of current and former fellows in OBG subspecialties
      report feeling prepared for fellowship in terms of clinical and surgical skills.
      Their feedback reveals opportunities for improvement of independent practice in
      gynecologic scenarios, as well as formal education on scientific research, for
      OBG residencies.

PMID- 30093333
TI  - A Facial Plastic and Reconstructive Surgery Training Module Using Surgical
      Simulation for Capacity Building.
AB  - OBJECTIVE: To introduce 3 novel intensive facial plastic and reconstructive
      surgery teaching modules for surgical capacity building using simulation in a low
      middle income country. DESIGN: Prospective cohort study. SETTING: University
      based medical center in Quito, Ecuador. PARTICIPANTS: First- and second-year
      otolaryngology residents in Quito, Ecuador. RESULTS: Residents participated in an
      intensive 3-day teaching program focused on microtia, nasoseptal abnormalities,
      and facial paralysis that included didactic lectures, simulation workshops, and
      live surgery. Residents underwent rigorous pre- and postmodule testing including
      written, oral, and practical examinations in each subject area. All participants
      completed anonymous feedback surveys with ratings on a Likert scale from 0 (very
      poor) to 10 (excellent). Nineteen residents completed both pre- and postmodule
      testing. The training module was successfully implemented and testing performance
      across all 3 subject areas significantly improved. Resident feedback was
      exceedingly positive, with average scores for each component ranging from 8.9 to
      9.8, with highest scores given to the simulation workshops. The postmodule survey
      indicated that all residents found the course helpful and they desired additional
      courses covering more subject areas. CONCLUSIONS: Implementation of an intensive
      surgical training module combining didactics, surgical simulation, and live
      surgery resulted in the successful transfer of both skills and knowledge. While
      the long-term benefit of this program is yet to be determined, this model of
      training may prove to be a useful tool to help address surgical capacity building
      in the developing world.

PMID- 30093334
TI  - A Structured Review Instrument Improves the Quality of Orthopaedic Journal Club.
AB  - OBJECTIVE: We asked the following questions: 1. Does the use of an structured
      review instrument (SRI) at journal club increase presentation quality, as
      measured objectively by a standardized evaluation rubric? 2. Does SRI use
      increase the time required to prepare for journal club? 3. Does SRI use
      positively impact presenter perceptions about confidence while presenting,
      satisfaction, and journal club effectiveness, as measured by postparticipation
      surveys? DESIGN: A prospective study was designed in which a grading rubric was
      developed to evaluate journal club presentations. The rubric was applied to 24
      presentations at journal clubs prior to introduction of the SRI. An SRI was
      developed and distributed to journal club participants, who were instructed to
      use it to prepare for journal club. The grading rubric was then used to assess 25
      post-SRI presentations and scores were compared between the pre- and post-SRI
      groups. Presentations occurred at either trauma, pediatrics, or spine
      subspecialty journal clubs. Participants were also surveyed regarding time
      requirements for preparation, perceptions of confidence while presenting,
      satisfaction, and perceptions of overall club effectiveness. SETTING: A single
      academic center with an orthopaedic surgery residency program. PARTICIPANTS:
      Resident physicians in the department of orthopaedic surgery. RESULTS: Mean
      presentation scores increased from 14.0 +/- 5.9 (mean +/- standard deviation) to
      24.4 +/- 5.2 after introduction of the SRI (p < 0.001). Preparation time
      decreased from a mean of 47 minutes to 40 minutes after SRI introduction (p =
      0.22). Perceptions of confidence, satisfaction, and club effectiveness among
      trainees trended toward more positive responses after SRI introduction
      (confidence: 63% positive responses pre-SRI vs 72% post-SRI, p = 0.73;
      satisfaction: 64% vs 91%, p = 0.18; effectiveness: 64% vs 91%, p = 0.19).
      CONCLUSIONS: The use of a structured review instrument to guide presentations at
      orthopaedic journal club increased presentation quality, and there was no
      difference in preparation time. There were trends toward improved presenter
      confidence, satisfaction, and perception of journal club effectiveness. SRI
      utilization at orthopaedic journal club may be an effective method for increasing
      the quality of journal club presentations. Future work should examine the
      relationship between presentation quality and overall club effectiveness.

PMID- 30093335
TI  - Evolution of Characteristics From Letters of Recommendation in General Surgery
      Residency Applications.
AB  - OBJECTIVE: Letters of recommendation (LOR) describe applicants being considered
      for Surgery Residencies. Although objective measures have been studied, the
      descriptive language of LOR and changes over time has yet to be evaluated. The
      objective of this study was to evaluate the descriptions of autonomy, teamwork,
      and ACGME core competencies in the LOR of applicants over time. DESIGN: After IRB
      approval, LOR of residents who matriculated into our Surgery Residency were
      evaluated. Residents were grouped into early (1973-1999) vs. late (2000-2016)
      applications, and generational groups (baby boomers: 1943-1960, generation X:
      1961-1980, millennial: 1981-1999), to identify the following themes: autonomy,
      teamwork, ACGME core competencies, and technical skills. Content analysis was
      performed using Nvivo 11. SETTING: Independent academic medical center.
      PARTICIPANTS: LOR from 76 of 77 residents who matriculated into our Surgery
      Residency from 1973-2016. RESULTS: 255 LOR were available. Autonomy was described
      175 times in 43 residents, and teamwork was described 263 times in 51 residents.
      Teamwork was more common in late vs. early applications (82% vs 53%; p = 0.007),
      and autonomy was present in 53% vs 61% of early vs late applications (p = 0.490).
      Teamwork was more commonly noted among millennial versus generation X and baby
      boomer applicants (92% vs 59% vs 47%; p = 0.006). Core competencies were detected
      1445 times, with an increase in systems-based practice, and practice-based
      learning and improvement in early versus late applications (0 vs 16%, p = 0.001;
      37% vs 74%, p = 0.025). Professionalism (68% vs 79%) and medical knowledge (74%
      vs 79%) were described consistently in early and late applications. Technical
      skills were described in 58% of early and 71% of late applications (p = 0.230).
      CONCLUSIONS: LOR for surgery residency applicants has evolved over time with
      increased teamwork concepts. Descriptions of practice-based learning, system
      based practice, research, and volunteerism have increased, while professionalism,
      medical knowledge, and technical skills were consistently described over time.

PMID- 30093337
TI  - Observation of Guided Acoustic Waves in a Human Skull.
AB  - Human skull poses a significant barrier for the propagation of ultrasound waves.
      Development of methods enabling more efficient ultrasound transmission into and
      from the brain is therefore critical for the advancement of ultrasound-mediated
      transcranial imaging or actuation techniques. We report on the first observation
      of guided acoustic waves in the near field of an ex vivo human skull specimen in
      the frequency range between 0.2 and 1.5MHz. In contrast to what was previously
      observed for guided wave propagation in thin rodent skulls, the guided wave
      observed in a higher-frequency regime corresponds to a quasi-Rayleigh wave,
      confined mostly to the cortical bone layer. The newly discovered near-field
      properties of the human skull are expected to facilitate the development of more
      efficient diagnostic and therapeutic techniques based on transcranial ultrasound.

PMID- 30093336
TI  - Does a Written Tool to Guide Structured Debriefing Improve Discourse?
      Implications for Interprofessional Team Simulation.
AB  - PURPOSE: Timely debriefing following a simulated event supports learners in
      critically reflecting on their performance and areas for improvement. Content of
      debriefing has been shown to affect learner skill acquisition and retention. The
      use of good judgment statements from debriefing facilitators is considered
      superior to judgmental or nonjudgmental statements. Ideally, the majority of the
      conversation will consist of learner self-reflection and focused facilitation
      rather than directive performance feedback. We hypothesized that the introduction
      of a written tool to help facilitate high-quality debriefing techniques could
      improve the ratio of judgmental, nonjudgmental, and good judgment statements from
      facilitators, as well as shift the percentage of talk in the debrief away from
      directive performance feedback and toward self-assessment and focused
      facilitation. METHODS: The University of Wisconsin Joint Trauma Simulation
      Program is an interdisciplinary project to improve quality of trauma care through
      simulation. Simulations use teams of five trauma trainees: two surgery residents,
      an emergency medicine resident, and two nurses. Three faculty members conducted
      the scenarios and debriefings. Debriefings were video recorded. Videos were
      transcribed and dialogue analyzed according to the teaching/learning strategy
      used in each turn of talk. Discourse was coded into three categories: (1) learner
      self-assessment; (2) focused facilitation; and (3) directive performance
      feedback. Each facilitation statement was coded as either (1) judgmental; (2)
      nonjudgmental, or (3) good judgment. The TEAM Debrief Tool is a written guide
      designed to help facilitators adhere to best practices, with example structure
      and phrasing, similar to the Promoting Excellence and Reflective Learning in
      Simulation tool. Pre- and post-implementation analysis was completed to assess
      for efficacy of the tool. RESULTS: Seven videos before the implementation of the
      tool and seven videos after implementation were analyzed. The percentage of
      learner self-assessment increased significantly with tool use (7.23% vs 24.99%, p
      = 0.00004), and directive performance feedback decreased significantly (56.13% vs
      32.75%, p = 0.0042). There was no significant change in the percentage of talk
      using focused facilitation. After implementation of the tool, there was a
      significant decrease in use of the nonjudgmental debriefing style (60.63% vs
      37.31%, p = 0.00017), and a significant increase in the use of good judgment
      debriefing (38.77% vs 59.82%, p = 0.00038). There was also a slight increase in
      judgmental debriefing (0.60% vs 2.87%, p = 0.0027). CONCLUSIONS: The discourse in
      our interprofessional trauma simulation debriefings unaided by a written
      debriefing tool skewed heavily toward direct performance feedback, with a
      preponderance of nonjudgmental statements. After introduction of the tool,
      dialogue shifted significantly toward learner self-assessment, and there was a
      large increase in utilization of debriefing with good judgment. This shift toward
      higher quality debriefing styles demonstrates the utility of such a tool in the
      debriefing of interprofessional simulations.

PMID- 30093338
TI  - Remote Echography between a Ground Control Center and the International Space
      Station Using a Tele-operated Echograph with Motorized Probe.
AB  - Echography is the most appropriate imaging modality for investigating astronauts.
      Unfortunately, it requires a great deal of training to perform ultrasound
      examinations, which can be difficult and time consuming, especially if the
      astronaut does not have a medical background. We designed a new echography system
      with motorized probes that allows for the majority of exam functions to be
      controlled by a ground-based sonographer. Using tele-operation, the sonographer
      controls the orientation of the transducer (tilt, rotation) and echograph
      settings (gain, depth, freeze) and triggers ultrasound functions (pulsed wave
      color Doppler, 3-D capture, radiofrequency data collection, elastography). With
      this system, astronauts are required to hold the motorized probe only at the
      locations indicated, with the remainder of the exam being conducted by the ground
      based sonographer. During spaceflight, ultrasound imaging of the carotid artery,
      jugular vein, thyroid, liver, gallbladder, biliary tract and portal vein (2-D, 3
      D, color, pulsed wave, radiofrequency) were successfully performed.

PMID- 30093339
TI  - Comparison Study of Low-Cost Ultrasound Devices for Estimation of Gestational Age
      in Resource-Limited Countries.
AB  - We investigated how accurately low-cost ultrasound devices can estimate
      gestational age (GA) using both the standard plane and the obstetric sweep
      protocol (OSP). The OSP can be taught to health care workers without prior
      knowledge of ultrasound within one day and thus avoid the need to train dedicated
      sonographers. Three low-cost ultrasound devices were compared with one high-end
      ultrasound device. GA was estimated with the head circumference (HC), abdominal
      circumference (AC) and femur length (FL) using both the standard plane and the
      OSP. The results revealed that the HC, AC and FL can be used to estimate GA using
      low-cost ultrasound devices in the standard plane within the inter-observer
      variability presented in the literature. The OSP can be used to estimate GA by
      measuring the HC and the AC, but not the FL. This study shows that it is feasible
      to estimate GA in resource-limited countries with low-cost ultrasound devices
      using the OSP. This makes it possible to estimate GA and assess fetal growth for
      pregnant women in rural areas of resource-limited countries.

PMID- 30093341
TI  - Power Spectrum Consistency among Systems and Transducers.
AB  - Use of the reference phantom method for computing acoustic attenuation and
      backscatter is widespread. However, clinical application of these methods has
      been limited by the need to acquire reference phantom data. We determined that
      the data acquired from 11 transducers of the same model and five clinical
      ultrasound systems of the same model produce equivalent estimates of reference
      phantom power spectra. We describe that the contribution to power spectral
      density variance among systems and transducers equals that from speckle variance
      with 59 uncorrelated echo signals. Thus, when the number of uncorrelated lines of
      data is small, speckle variance will dominate the power spectral density estimate
      variance introduced by different systems and transducers. These results suggest
      that, at least for this particular transducer and imaging system combination, one
      set of reference phantom calibration data is highly representative of the average
      among equivalent transducers and systems that are in good working order.

PMID- 30093340
TI  - Non-invasive Characterization of Focal Arrhythmia with Electromechanical Wave
      Imaging in Vivo.
AB  - There is currently no established method for the non-invasive characterization of
      arrhythmia and differentiation between endocardial and epicardial triggers at the
      point of care. Electromechanical wave imaging (EWI) is a novel ultrasound-based
      imaging technique based on time-domain transient strain estimation that can map
      and characterize electromechanical activation in the heart in vivo. The
      objectives of this initial feasibility study were to determine that EWI is
      capable of differentiating between endocardial and epicardial sources of focal
      rhythm and, as a proof-of-concept, that EWI could characterize focal arrhythmia
      in one patient with premature ventricular contractions (PVCs) before
      radiofrequency (RF) ablation treatment. First, validation of EWI for
      differentiation of surface of origin was performed in seven (n = 7) adult dogs
      using four epicardial and four endocardial pacing protocols. Second, one (n = 1)
      adult patient diagnosed with PVC was imaged with EWI before the scheduled RF
      ablation procedure, and EWI results were compared with mapping procedure results.
      In dogs, EWI was capable of detecting whether pacing was of endocardial or
      epicardial origin in six of seven cases (86% success rate). In the PVC patient,
      EWI correctly identified both regions and surface of origin, as confirmed by
      results from the electrical mapping obtained from the RF ablation procedure.
      These results reveal that EWI can map the electromechanical activation across the
      myocardium and indicate that EWI could serve as a valuable pre-treatment planning
      tool in the clinic.

PMID- 30093342
TI  - Resting-State Connectivity and Its Association With Cognitive Performance,
      Educational Attainment, and Household Income in the UK Biobank.
AB  - BACKGROUND: Cognitive ability is an important predictor of lifelong physical and
      mental well-being, and impairments are associated with many psychiatric
      disorders. Higher cognitive ability is also associated with greater educational
      attainment and increased household income. Understanding neural mechanisms
      underlying cognitive ability is of crucial importance for determining the nature
      of these associations. In the current study, we examined the spontaneous activity
      of the brain at rest to investigate its relationships with not only cognitive
      ability but also educational attainment and household income. METHODS: We used a
      large sample of resting-state neuroimaging data from the UK Biobank (n = 3950).
      RESULTS: First, analysis at the whole-brain level showed that connections
      involving the default mode network (DMN), frontoparietal network (FPN), and
      cingulo-opercular network (CON) were significantly positively associated with
      levels of cognitive performance assessed by a verbal-numerical reasoning test
      (standardized beta cingulo-opercular values ranged from 0.054 to 0.097,
      pcorrected < .038). Connections associated with higher levels of cognitive
      performance were also significantly positively associated with educational
      attainment (r = .48, n = 4160) and household income (r = .38, n = 3793).
      Furthermore, analysis on the coupling of functional networks showed that better
      cognitive performance was associated with more positive DMN-CON connections,
      decreased cross-hemisphere connections between the homotopic network in the CON
      and FPN, and stronger CON-FPN connections (absolute betas ranged from 0.034 to
      0.063, pcorrected < .045). CONCLUSIONS: The current study found that variation in
      brain resting-state functional connectivity was associated with individual
      differences in cognitive ability, largely involving the DMN and lateral
      prefrontal network. In addition, we provide evidence of shared neural
      associations of cognitive ability, educational attainment, and household income.

PMID- 30093343
TI  - Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in
      Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance
      Use, and Hepatitis C Coinfection.
AB  - BACKGROUND: Life expectancy of successfully treated human immunodeficiency virus
      (HIV)-infected individuals is approaching normal longevity. The growing HIV
      population >=50 years of age is now at risk of developing HIV-associated
      neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV),
      and engaging in hazardous drinking or drug consumption that can adversely affect
      trajectories of the healthy aging of brain structures. METHODS: This cross
      sectional/longitudinal study quantified regional brain volumes from 1101 magnetic
      resonance imaging scans collected over 14 years in 549 participants (25 to 75
      years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV
      infected individuals with alcohol dependence, 222 alcohol-dependent individuals,
      and 199 control subjects. We tested 1) whether localized brain regions in HIV
      infected individuals exhibited accelerated aging, or alternatively,
      nonaccelerated premature aging deficits; and 2) the extent to which alcohol or
      substance dependence or HCV coinfection altered brain aging trajectories.
      RESULTS: The HIV-infected cohort exhibited steeper declining volume trajectories
      than control subjects, consistently in the frontal cortex. Nonaccelerated volume
      deficits occurred in the temporal, parietal, insular, and cingulate regions of
      all three diagnostic groups. Alcohol and drug dependence comorbidities and HCV
      coinfection exacerbated HIV-related volume deficits. Accelerated age interactions
      in frontal and posterior parietal volumes endured in HIV-infected individuals
      free of alcohol or substance dependence and HCV infection comorbidities.
      Functionally, poorer HIV-associated neurocognitive disorder scores and Veterans
      Aging Cohort Study indices correlated with smaller regional brain volumes in the
      HIV-infected individuals without alcohol dependence and alcohol-dependent groups.
      CONCLUSIONS: HIV infection itself may confer a heightened risk of accelerated
      brain aging, potentially exacerbated by HCV coinfection and substance dependency.
      Confirmation would require a prospective study with a preinfection baseline.

PMID- 30093344
TI  - Biophysical Modeling of Large-Scale Brain Dynamics and Applications for
      Computational Psychiatry.
AB  - Noninvasive neuroimaging has revolutionized the study of the organization of the
      human brain and how its structure and function are altered in psychiatric
      disorders. A critical explanatory gap lies in our mechanistic understanding of
      how systems-level neuroimaging biomarkers emerge from underlying synaptic-level
      perturbations associated with a disease state. We describe an emerging
      computational psychiatry approach leveraging biophysically based computational
      models of large-scale brain dynamics and their potential integration with
      clinical and pharmacological neuroimaging. In particular, we focus on neural
      circuit models, which describe how patterns of functional connectivity observed
      in resting-state functional magnetic resonance imaging emerge from neural
      dynamics shaped by inter-areal interactions through underlying structural
      connectivity defining long-range projections. We highlight the importance of
      local circuit physiological dynamics, in combination with structural
      connectivity, in shaping the emergent functional connectivity. Furthermore,
      heterogeneity of local circuit properties across brain areas, which impacts large
      scale dynamics, may be critical for modeling whole-brain phenomena and
      alterations in psychiatric disorders and pharmacological manipulation. Finally,
      we discuss important directions for future model development and biophysical
      extensions, which will expand their utility to link clinical neuroimaging to
      neurobiological mechanisms.

PMID- 30093345
TI  - Novel benzodiazepines derivatives as analgesic modulating for Transient receptor
      potential vanilloid 1.
AB  - A new series of derivatives of 3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro
      1H-benzo[e][1,4]diazepin-3-yl)propanoic acid were designed and synthesized as
      analgesic modulating for Transient receptor potential vanilloid 1. They were
      investigated for TRPV1 antagonistic activity in vitro, analgesic activity and
      sedative activity in vivo and aqueous solubility. Preliminary studies identified
      3-(7-chloro-5-(2-fluorophenyl)-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)
      N,N-dimethylpropanamide(Compound 11), as a potent analgesic modulating for TRPV1
      with potent activity and good aqueous solubility.

PMID- 30093346
TI  - Decoy peptides derived from the extracellular domain of toll-like receptor 2
      (TLR2) show anti-inflammatory properties.
AB  - Toll-like receptor 2 (TLR2) recognizes bacterial derived- and synthetic
      lipopeptides after dimerization with TLR1 or TLR6. Hyper-activation of TLR2 has
      been described in several inflammatory diseases and the discovery of inhibitors
      of its pro-inflammatory activity represent potential starting points to develop
      therapeutics in such pathologies. We designed peptides derived from the TLR2
      sequence comprising amino acid residues involved in ligand binding (Pam3CSK4) or
      heterodimerization (TLR2/TLR1) as pointed out by structural data.2 We identified
      several peptides (P13, P13(LL), P16, P16(LL)) which inhibited TLR2/1 signaling in
      HEK293-TLR2 cells (MAPK activation and NF-kB activity). Moreover, P13L and P16L
      decreased TNFalpha release in human primary PBMCs and mouse macrophages. The
      peptides were selective for TLR2/1 as they did not inhibit the activity of other
      TLRs tested. P13L and P16L inhibited the internalization of Pam3CSK4
      fluorescently labeled in macrophages and the heterodimerization of TLR2 with TLR1
      as demonstrated by immunoprecipitation studies. Our data demonstrate that
      peptides derived from the region comprising the leucine-rich repeats (LRR) 11 and
      13 in the extracellular domain of TLR2 are good starting points to develop more
      potent anti-inflammatory peptides with TLR2 inhibitory activity.

PMID- 30093347
TI  - Synthesis and biological evaluation of novel benzofuroxan-based pyrrolidine
      hydroxamates as matrix metalloproteinase inhibitors with nitric oxide releasing
      activity.
AB  - On the basis of the strategy of "multifunctional drugs", a series of novel matrix
      metalloproteinase inhibitors (MMPIs) containing benzofuroxan scaffold as a nitric
      oxide donor were designed, synthesized and evaluated. All synthesized compounds,
      especially 16a, exhibited potent MMP-2,9 inhibitory activities, anti
      proliferative activities and could produce high levels of NO in Hela cells. They
      were also evaluated for both of their anti-invasion and anti-angiogenesis
      effects. Furthermore, compared with LY52, 16a demonstrated competitive antitumor
      activity in vivo. These hybrid NO-MMPIs might offer suitable scaffolds to develop
      valuable MMP inhibitors for the further discovery of novel anti-cancer drugs.

PMID- 30093348
TI  - Gestational weight gain and unplanned or emergency cesarean delivery in the
      United States.
AB  - BACKGROUND: In the United States, the rates of cesarean delivery are well above
      the World Health Organization recommended target. Although obesity is a widely
      established risk factor for cesarean delivery, there is limited population-based
      research that examines the relationship between gestational weight gain and
      cesarean delivery. OBJECTIVE: To determine the association between gestational
      weight gain and unplanned or emergency cesarean delivery. METHODS: We examined
      2107 mothers from the Infant Feeding Practices Study II 2005-2007. The Institute
      of Medicine's current guidelines were used to define categories of gestational
      weight gain: inadequate (less than the recommended guideline), adequate (within
      the recommended guideline) and excessive (above the recommended guideline).
      FINDINGS: Approximately 49.3% and 13.6% of the participants had excessive weight
      gain and unplanned or emergency cesarean delivery, respectively. A Greater
      proportion of women with excessive weight gain had an unplanned or emergency
      cesarean delivery followed by women with adequate and inadequate weight gain,
      respectively (17.8%, 10.0%, 8.8%; p<0.001). In the multivariable model, compared
      to women with adequate weight gain, the odds of unplanned or emergency cesarean
      delivery were higher among women with excessive weight gain (OR 1.56, 95% CI 1.07
      2.27, p=0.020). DISCUSSION: Women with excessive gestational weight gain are more
      likely to experience an unplanned or emergency cesarean delivery, which increases
      the risk for poor maternal-infant health outcomes. CONCLUSION: It is critical to
      identify populations at increased risk of unplanned or emergency cesarean
      delivery and provide preconception and prenatal counseling to achieve and
      maintain the recommended weight gain for optimal maternal-infant health outcomes.

PMID- 30093349
TI  - Midwives 'with woman' in the private obstetric model: Where divergent
      philosophies meet.
AB  - BACKGROUND: The phenomenon of being 'with woman' is central to the profession of
      midwifery. There is currently no available evidence that explicitly explores this
      phenomenon. In Western Australia, over a third of childbearing women choose to
      engage the services of a private obstetrician who provides antenatal care and
      manages the care provided by midwives during labour and birth. AIM: The aim of
      this study was to explore midwives' experiences of being 'with woman' during
      labour and birth in the private obstetric model. METHODS: Using a descriptive
      phenomenological approach, 11 midwives working in the private obstetric model in
      Western Australia were interviewed. Data analysis was conducted using Giorgi's
      framework. FINDINGS: Two main themes emerged (1) triad of relationships and (2)
      the intersection between being 'with woman' and the private obstetric model;
      seven subthemes are reported. DISCUSSION: Being 'with woman' is an important
      element of midwifery practice and fundamental to midwifery theory and philosophy.
      Relationships between the woman, midwife and obstetrician are key to implementing
      'with woman' practices in the private obstetric model. The interrelatedness of
      midwifery philosophy and practice is revealed through shared common challenges
      and enablers to being 'with woman' from the perspective of midwives. CONCLUSION:
      Findings offer insight into midwives' experiences of being 'with woman' within
      the context of the private obstetric model. New understandings are revealed of a
      phenomenon central to midwifery professional philosophy that is embedded within
      midwifery practices which has implications for service mangers, professional
      leaders and educators.

PMID- 30093351
TI  - Social reward processing: A biomarker for predicting psychosis risk?
AB  - The desire to obtain social rewards (e.g. positive feedback) features prominently
      in our lives and relationships, and is relevant to understanding psychopathology 
      where behavior is often impaired. Investigating social rewards within the
      psychosis-spectrum offers an especially useful opportunity, given the high rates
      of impaired social functioning and social isolation. The goal of this study was
      to investigate hedonic experience associated with social reward processing as a
      potential biomarker for psychosis risk. This study used a task-based functional
      magnetic resonance imaging (fMRI) paradigm in adolescents at clinical high-risk
      for the development of psychosis (CHR, n = 19) and healthy unaffected peers
      (healthy controls - HC, n = 20). Regional activation and connectivity of the
      ventromedial prefrontal cortex and ventral striatum were examined in response to
      receiving positive social feedback relative to an ambiguous feedback condition.
      Expectations of impaired hedonic processes in CHR youth were generally not
      supported, as there were no group differences in neural response or task-based
      connectivity. Although interesting relationships were found linking neural reward
      response and connectivity with social, anticipatory, and consummatory anhedonia
      in the CHR group, results are difficult to interpret in light of task
      limitations. We discuss potential implications for future study designs that seek
      to investigate social reward processing as a biomarker for psychosis risk.

PMID- 30093350
TI  - Diminished modulation of motor cortical reactivity during context-based action
      observation in schizophrenia.
AB  - BACKGROUND: Deficient mirror neuron system (MNS)-activity is associated with
      social cognition deficits in schizophrenia. However, it is not known how socio
      emotional contexts modulate the MNS-response. In a Transcranial Magnetic
      Stimulation (TMS)-experiment, we aimed to compare putative MNS-responses to
      action observation stimuli with and without a context, in patients with
      schizophrenia and healthy subjects. METHOD: TMS-evoked motor cortical reactivity
      was measured by single and paired [short interval intracortical inhibition (SICI)
      and facilitation (ICF)] pulse-paradigms in schizophrenia patients (n = 39) and
      healthy subjects (n = 28) while they observed three experimental-blocks: a static
      image, a neutral hand action (NA) and a context-based hand action (CA). The
      degree of cortical reactivity facilitation with the two action observation
      blocks, relative to the static block provided indirect measures of premotor MNS
      activity. A subset of patients (n = 31) also underwent comprehensive social
      cognition assessments. RESULTS: RMANOVA demonstrated significantly higher
      cortical reactivity during the CA-block in both groups (all TMS-paradigms);
      albeit significantly less pronounced in patients (SICI and ICF paradigms). MNS
      activity during the CA-block was significantly higher compared to that during the
      NA-block in both groups (all TMS-paradigms), but significantly less pronounced in
      patients (SICI and single-pulse paradigms). MNS-activity during the CA-block
      measured by the ICF paradigm was positively correlated with social cognition
      performance. CONCLUSION: Providing a context to the action modulates MNS
      activity. This modulation is diminished in schizophrenia patients, suggestive of
      a diminished sensorimotor associative learning process. This novel, ecologically
      valid paradigm to tap into the MNS may serve as a neuro-marker of social
      cognition performance in schizophrenia.

PMID- 30093353
TI  - Endoscopic ultrasound elastography in the diagnosis of pancreatic masses: A meta
      analysis.
AB  - BACKGROUND AND AIMS: Endoscopic ultrasound (EUS) elastography is a novel non
      invasive technique that can be used for distinguishing benign from malignant
      pancreatic masses. However, the studies have reported widely varied sensitivities
      and specificities. A meta-analysis was performed to assess the performance of EUS
      elastography for the differentiation of benign and malignant pancreatic masses.
      METHODS: All the eligible studies were searched by PubMed, Medline, Embase, and
      the Cochrane Library. Sensitivity, specificity, positive likelihood ratio (LR),
      negative LR, and area under the curve (AUC) were calculated to examine the
      accuracy. RESULTS: A total of nineteen studies which included 1687 patients were
      analyzed. The pooled sensitivity and specificity for the diagnosis of malignant
      pancreatic masses were 0.98 (95% confidence interval [CI] 0.96-0.99) and 0.63
      (95% CI 0.58-0.69) for qualitative EUS elastography, 0.95 (95% CI 0.93-0.97) and
      0.61 (95% CI 0.56-0.66) for quantitative EUS elastography, respectively. The
      positive and negative LR were 2.60 (95% CI 1.84-3.66) and 0.05 (95% CI 0.02-0.10)
      for qualitative EUS elastography, 2.64 (95% CI 1.82-3.82) and 0.10 (95% CI 0.06
      0.16) for quantitative EUS elastography, respectively. The summary diagnostic
      odds ratio (DOR) and the AUC were 60.59 (95% CI 28.12-130.56) and 0.91 (Q* =
      0.842) for qualitative EUS elastography, 30.09 (95% CI 15.40-58.76) and 0.93 (Q*
      = 0.860) for quantitative EUS elastography. CONCLUSIONS: Our meta-analysis shows
      that both qualitative and quantitative EUS elastography have high accuracy in the
      detection of malignant pancreatic masses, which could be used as a valuable
      complementary method to EUS-FNA for the differentiation of pancreatic masses in
      the future.

PMID- 30093352
TI  - Attention deficit hyperactivity disorder symptoms as antecedents of later
      psychotic outcomes in 22q11.2 deletion syndrome.
AB  - Individuals with 22q11.2 Deletion Syndrome (22q11.2DS) are at substantially
      heightened risk for psychosis. Thus, prevention and early intervention strategies
      that target the antecedents of psychosis in this high-risk group are a clinical
      priority. Attention Deficit Hyperactivity Disorder (ADHD) is one the most
      prevalent psychiatric disorders in children with 22q11.2DS, particularly the
      inattentive subtype. The aim of this study was to test the hypothesis that ADHD
      inattention symptoms predict later psychotic symptoms and/or psychotic disorder
      in those with 22q11.2DS. 250 children and adolescents with 22q11.2DS without
      psychotic symptoms at baseline took part in a longitudinal study. Assessments
      were performed using well-validated structured diagnostic instruments at two time
      points (T1 (mean age = 11.2, SD = 3.1) and T2 (mean age = 14.3, SD = 3.6)).
      Inattention symptoms at T1 were associated with development of psychotic symptoms
      at T2 (OR:1.2, p = 0.01) but weak associations were found with development of
      psychotic disorder (OR:1.2, p = 0.15). ADHD diagnosis at T1 was strongly
      associated with development of psychotic symptoms at T2 (OR:4.5, p < 0.001) and
      psychotic disorder (OR:5.9, p = 0.02). Our findings that inattention symptoms and
      the diagnosis of ADHD are associated with subsequent psychotic outcomes in
      22q11.2DS have important clinical implications. Future studies examining the
      effects of stimulant and other ADHD treatments on individuals with 22q11.2DS are
      warranted.

PMID- 30093354
TI  - 21-gene recurrence score testing in the older population with estrogen receptor
      positive breast cancer.
AB  - INTRODUCTION: The 21-gene recurrence score (RS) (Oncotype Dx, Genomic Health,
      Redwood City Ca) has not been validated in an older cohort with estrogen receptor
      (ER)-positive breast cancer. The objective of this study was to evaluate RS
      validity in a group of older women with ER-positive breast cancer. METHODS:
      Utilizing the Surveillance, Epidemiology, and End Results Program (SEER) database
      with available RS, we evaluated women with ER-positive breast cancer aged 18-69
      and those 70 years of age and older from 2004 to 2014. We utilized multivariable
      logistic regression models to evaluate factors associated with RS testing as well
      as a high-risk categorization for those who underwent testing. Survival was
      analyzed using Kaplan Meier curves and Cox proportional hazard models. RESULTS:
      We identified 363,876 women aged 18-69 years and 147,107 women aged 70 years and
      older. A smaller proportion of patients in the older group (8%) underwent RS
      testing than in the younger group (18%). Of the patients who underwent testing,
      distribution of RS was similar between groups. High-risk categorization
      independently predicted a higher likelihood of death for older patients (hazard
      ratio 1.47, 95% confidence interval 1.15-1.90). Among patients with high-risk RS,
      chemotherapy was associated with a decreased risk of death in the younger group,
      but not in the older group. CONCLUSION: Older women are less likely to receive RS
      testing, but when tested, older patients have a similar distribution of RS as
      compared to younger patients. While high-risk categorization in the older cohort
      was prognostic, chemotherapy was not associated with improved survival.

PMID- 30093355
TI  - AMPK activation negatively regulates GDAP1, which influences metabolic processes
      and circadian gene expression in skeletal muscle.
AB  - OBJECTIVE: We sought to identify AMPK-regulated genes via bioinformatic analysis
      of microarray data generated from skeletal muscle of animal models with
      genetically altered AMPK activity. We hypothesized that such genes would play a
      role in metabolism. Ganglioside-induced differentiation-associated protein 1
      (GDAP1), a gene which plays a role in mitochondrial fission and peroxisomal
      function in neuronal cells but whose function in skeletal muscle is undescribed,
      was identified and further validated. AMPK activation reduced GDAP1 expression in
      skeletal muscle. GDAP1 expression was elevated in skeletal muscle from type 2
      diabetic patients but decreased after acute exercise. METHODS: The metabolic
      impact of GDAP1 silencing was determined in primary skeletal muscle cells via
      siRNA-transfections. Confocal microscopy was used to visualize whether silencing
      GDAP1 impacted mitochondrial network morphology and membrane potential. RESULTS:
      GDAP1 silencing increased mitochondrial protein abundance, decreased palmitate
      oxidation, and decreased non-mitochondrial respiration. Mitochondrial morphology
      was unaltered by GDAP1 silencing. GDAP1 silencing and treatment of cells with
      AMPK agonists altered several genes in the core molecular clock machinery.
      CONCLUSION: We describe a role for GDAP1 in regulating mitochondrial proteins,
      circadian genes, and metabolic flux in skeletal muscle. Collectively, our results
      implicate GDAP1 in the circadian control of metabolism.

PMID- 30093359
TI  - Vaccine Development for Urinary Tract Infections: Where Do We Stand?
AB  - Urinary tract infections (UTIs) are among the most common bacterial infections.
      Its management has become increasingly challenging due to antimicrobial
      resistance. The four mainstays to tackle this crisis rely on the development of
      new antibiotic agents, the introduction of preventive and alternative
      antimicrobial strategies, the concept of antimicrobial stewardship, and effective
      hygiene measures. One of the most effective approaches to prevent UTIs is the
      design of a potent vaccine. OM-89 is a lyophilised preparation of membrane
      proteins from 18 different uropathogenic Escherichia coli strains. The safety and
      efficacy of this immunoactive agent is well documented; therefore, it is
      recommended for the prophylaxis of UTI according to the current European
      Association of Urology guidelines on urological infections. In terms of a true
      vaccine designed to target specifically pathogenic bacteria, no substance is
      currently available. ExPEC4V, a novel tetravalent bioconjugate vaccine against
      extraintestinal pathogenic E. coli, was evaluated for safety, immunogenicity, and
      clinical efficacy in a randomised, single-blinded, placebo-controlled phase 1b
      trial. The vaccine was well tolerated and elicited a robust antibody response in
      patients suffering from recurrent UTIs. Although the first clinical data
      suggested a reduced incidence of UTIs after vaccination, especially for higher
      bacterial loads, further randomised controlled trials are necessary to determine
      its true clinical benefit.

PMID- 30093356
TI  - Chronic d-serine supplementation impairs insulin secretion.
AB  - OBJECTIVE: The metabolic role of d-serine, a non-proteinogenic NMDA receptor co
      agonist, is poorly understood. Conversely, inhibition of pancreatic NMDA
      receptors as well as loss of the d-serine producing enzyme serine racemase have
      been shown to modulate insulin secretion. Thus, we aim to study the impact of
      chronic and acute d-serine supplementation on insulin secretion and other
      parameters of glucose homeostasis. METHODS: We apply MALDI FT-ICR mass
      spectrometry imaging, NMR based metabolomics, 16s rRNA gene sequencing of gut
      microbiota in combination with a detailed physiological characterization to
      unravel the metabolic action of d-serine in mice acutely and chronically treated
      with 1% d-serine in drinking water in combination with either chow or high fat
      diet feeding. Moreover, we identify SNPs in SRR, the enzyme converting L-to d
      serine and two subunits of the NMDA receptor to associate with insulin secretion
      in humans, based on the analysis of 2760 non-diabetic Caucasian individuals.
      RESULTS: We show that chronic elevation of d-serine results in reduced high fat
      diet intake. In addition, d-serine leads to diet-independent hyperglycemia due to
      blunted insulin secretion from pancreatic beta cells. Inhibition of alpha 2
      adrenergic receptors rapidly restores glycemia and glucose tolerance in d-serine
      supplemented mice. Moreover, we show that single nucleotide polymorphisms (SNPs)
      in SRR as well as in individual NMDAR subunits are associated with insulin
      secretion in humans. CONCLUSION: Thus, we identify a novel role of d-serine in
      regulating systemic glucose metabolism through modulating insulin secretion.

PMID- 30093357
TI  - Exercise-induced molecular mechanisms promoting glycogen supercompensation in
      human skeletal muscle.
AB  - OBJECTIVE: A single bout of exercise followed by intake of carbohydrates leads to
      glycogen supercompensation in prior exercised muscle. Our objective was to
      illuminate molecular mechanisms underlying this phenomenon in skeletal muscle of
      man. METHODS: We studied the temporal regulation of glycogen supercompensation in
      human skeletal muscle during a 5 day recovery period following a single bout of
      exercise. Nine healthy men depleted (day 1), normalized (day 2) and
      supercompensated (day 5) muscle glycogen in one leg while the contralateral leg
      served as a resting control. Euglycemic hyperinsulinemic clamps in combination
      with leg balance technique allowed for investigating insulin-stimulated leg
      glucose uptake under these 3 experimental conditions. Cellular signaling in
      muscle biopsies was investigated by global proteomic analyses and immunoblotting.
      We strengthened the validity of proposed molecular effectors by follow-up studies
      in muscle of transgenic mice. RESULTS: Sustained activation of glycogen synthase
      (GS) and AMPK in combination with elevated expression of proteins determining
      glucose uptake capacity were evident in the prior exercised muscle. We
      hypothesize that these alterations offset the otherwise tight feedback inhibition
      of glycogen synthesis and glucose uptake by glycogen. In line with key roles of
      AMPK and GS seen in the human experiments we observed abrogated ability for
      glycogen supercompensation in muscle with inducible AMPK deletion and in muscle
      carrying a G6P-insensitive form of GS in muscle. CONCLUSION: Our study
      demonstrates that both AMPK and GS are key regulators of glycogen
      supercompensation following a single bout of glycogen-depleting exercise in
      skeletal muscle of both man and mouse.

PMID- 30093358
TI  - Robot-assisted Kidney Autotransplantation: A Minimally Invasive Way to Salvage
      Kidneys.
AB  - BACKGROUND: Kidney autotransplantation (KAT) is the ultimate way to salvage
      kidneys with complex renovascular, ureteral, or malignant pathologies that are
      not amenable to in situ reconstruction. A minimally invasive approach could
      broaden its adoption. OBJECTIVE: To describe operative technique, perioperative
      complications, and early functional outcomes of robot-assisted kidney
      autotransplantation (RAKAT). DESIGN, SETTING, AND PARTICIPANTS: Retrospective
      review of prospectively collected data regarding consecutive patients undergoing
      RAKAT between March 2017 and February 2018 at two university hospitals.
      INTERVENTION: RAKAT. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Technical
      feasibility, perioperative complications, and early functional results. RESULTS
      AND LIMITATIONS: Seven patients underwent RAKAT (three male and four female; five
      left and two right; one totally intracorporeal) for complex ureteral strictures
      (n=5), severe left renal vein nutcracker (n=1), and loin pain hematuria syndrome
      (n=1). Two patients underwent bench vascular reconstruction and one patient
      underwent ex vivo flexible ureterorenoscopy. No patient needed open conversion.
      Median operative and console time was 370 and 255min, respectively, with median
      vascular and ureteral anastomosis time of 28 and 23min, respectively. Median
      warm, cold, and rewarming ischemia time was 2, 178, and 44min, respectively. One
      major postoperative complication occurred-wound dehiscence needing wound revision
      (grade 3b). Median hospital stay was 5 d. At 3 mo, all patients were free of
      indwelling stents, pain, or hematuria. Median serum creatinine at 3 mo was
      0.80mg/dl and median calculated autotransplant glomerular filtration rate did not
      drop significantly. CONCLUSIONS: RAKAT is feasible, safe, and results in good
      functioning of the autotransplant in selected patients with complex ureteral
      strictures, loin pain hematuria, or severe nutcracker syndrome. Larger studies
      with longer follow-up are needed to confirm these findings and to test whether
      RAKAT is feasible for other KAT indications. PATIENT SUMMARY: We describe the
      first series worldwide of a minimally invasive technique for kidney
      autotransplantation. Robot-assisted kidney autotransplantation is a safe and
      feasible approach to prevent nephrectomy for intractable symptoms in selected
      patients with complex ureteral or renal pathology.

PMID- 30093362
TI  - Associations between sleep duration and suicidality in adolescents: A systematic
      review and dose-response meta-analysis.
AB  - Sleep duration has received considerable attention as a potential risk factor of
      suicidality in youths; however, evidence on the dose-response association between
      sleep duration and suicidality has not been synthesized. This meta-analysis
      examined linear and nonlinear dose-response relationships between sleep duration
      and the risk of suicidality in adolescents and explored potential moderators of
      the associations. Electronic databases, namely EMBASE, PubMed, PsycINFO, ProQuest
      Dissertations & Theses A&I Wanfang Data (Chinese database), and the China
      Knowledge Resource Integrated Database, were searched from their inception to
      April 18, 2017. Studies examining the association between sleep duration and
      suicidality in adolescents were included. A random-effects dose-response model
      was used to estimate the linear and nonlinear dose-response relationships. We
      identified 13 reports that included a total of 598,281 participants for a
      systematic review, and 12 reports were further used for a dose-response meta
      analysis. Strong curvilinear dose-response associations were obtained for both
      suicidal ideation and attempts, with the lowest suicidal ideation and attempt
      risks at sleep durations of 8 h and 8-9 h per day (all Pnonlinearity < 0.001). A
      linear dose-response relationship between sleep duration and suicide plans
      (pooled OR = 0.89, 95% confidence interval [CI] = 0.88-0.90) was obtained,
      indicating that the risk of suicide plans statistically decreased by 11% for
      every 1-h increase in sleep duration. Depression did not moderate the association
      between sleep duration and suicidality in youths. Our findings suggest
      curvilinear dose-response associations between sleep duration and the risks of
      suicidal ideation and attempts and a linear dose-response relationship between
      sleep duration and suicide plan risk. Additional longitudinal studies are
      warranted to establish causality.

PMID- 30093360
TI  - Sleep disturbances and their impact in pediatric cystic fibrosis.
AB  - Cystic fibrosis is a chronic, life-shortening illness that affects multiple
      systems and results in frequent respiratory infections, chronic cough, fat
      malabsorption and malnutrition. Poor sleep is often reported by patients with
      cystic fibrosis. Although objective data to explain these complaints have been
      limited, they do show poor sleep efficiency and frequent arousals. Abnormalities
      in gas exchange are also observed during sleep in patients with cystic fibrosis.
      The potential impact of these abnormalities in sleep on health and quality of
      life remains largely unstudied. This review summarizes what is known about sleep
      in children with cystic fibrosis, and implications for clinical practice. This
      report also highlights new evidence on the impact of sleep problems on disease
      specific outcomes such as lung function, and identifies areas that need further
      exploration.

PMID- 30093361
TI  - A lack of consistent brain alterations in insomnia disorder: An activation
      likelihood estimation meta-analysis.
AB  - Insomnia disorder is a prevalent sleep disorder, which affects about 10% of
      general population. However, its neural mechanisms are poorly understood.
      Recently, several structural and functional neuroimaging studies have been
      conducted in patients with insomnia disorder, but these studies have yielded
      diverse findings. Here, we aimed to identify consistent patterns of abnormal
      brain alterations in insomnia disorder by performing a quantitative coordinate
      based meta-analysis. Following the preferred reporting for systematic reviews and
      meta-analyses statement, we searched PubMed database and used reference tracking
      and finally retrieved 19 eligible studies (six task-based functional magnetic
      resonance imaging, eight resting-state functional magnetic resonance imaging,
      three voxel-based morphometry, and two positron emission tomography). We
      extracted peak coordinates from these studies and tested for convergence using
      the activation likelihood estimation method. Using this method, we found no
      significant convergent evidence for combination of structural atrophy and
      functional disturbances across previous studies (p = 0.914). Inconsistencies
      across these studies might be related to heterogonous clinical populations, the
      explorative nature of these studies in combination with small sample sizes,
      different experimental designs, and various preprocessing and statistical
      approaches. Future neuroimaging studies on insomnia disorder should include
      larger well-characterized samples, as well as standard imaging and analysis
      protocols.

PMID- 30093364
TI  - Variations in the Delivery of Emergency General Surgery Care in the Era of Acute
      Care Surgery.
AB  - BACKGROUND: Acute care surgery (ACS) was proposed to improve emergency general
      surgery (EGS) care; however, the extent of ACS model adoption in the United
      States is unknown. A national survey was conducted to ascertain factors
      associated with variations in EGS models of care, with particular focus on ACS
      use. METHODS: A hybrid mail/electronic survey was sent in 2015 to 2,811 acute
      care hospitals with an emergency room and an operating room. If a respondent
      indicated that the approach to EGS was a dedicated clinical team whose scope
      encompasses EGS (+/- trauma, +/- elective general surgery, +/- burns), the
      hospital was considered an ACS hospital. RESULTS: Survey response was 60.1% (n =
      1,690); 272 (16.1%) of these hospitals reported having used an ACS model of care
      for EGS patients. Teaching status and general hospital practices (for example,
      interventional radiology available within one hour) were associated with ACS use.
      In bivariate analyses, ACS use was associated with many EGS-specific practices
      (40.1% of ACS hospitals freed their surgeons of daytime clinical responsibilities
      after operating overnight vs. 4.7% of general surgeon on call (GSOC) hospitals; p
      < 0.0001). CONCLUSION: There are wide variations in EGS practices in the United
      States, with use of an ACS model of care being relatively low despite reported
      benefits of ACS models of care on EGS access, quality, and costs. Hospital
      factors associated with using ACS models are overall size and higher level of
      existing resources. These findings could be applied to the development of centers
      of excellence for EGS care.

PMID- 30093363
TI  - Clinical correlates of decreased plasma coenzyme Q10 levels in patients with
      multiple system atrophy.
AB  - INTRODUCTION: Multiple system atrophy (MSA) is a progressive neurodegenerative
      disease. Recent studies revealed decreased coenzyme Q10 (COQ10) levels in the
      cerebellum and blood samples of MSA patients. But few studies focused on the
      associations of COQ10 with the clinical symptoms of MSA. In this study, we aimed
      to quantify plasma COQ10 and characterize its association with clinical features.
      METHODS: We recruited 40 patients with MSA, 30 patients with Parkinson's disease
      (PD), and 30 healthy participants. Plasma COQ10 was quantified by UPLC-MS. The
      basic demographic data, motor symptoms, and non-motor symptoms were also
      assessed. RESULTS: Plasma COQ10 levels were significantly different in MSA, PD,
      and controls (P = 0.001). Post-hoc analysis revealed plasma COQ10 levels in MSA
      patients were lower than that in controls after adjusting for age, gender, and
      total cholesterol (P = 0.001). COQ10 levels differentiated MSA patients from
      controls with modest accuracy (P = 0.001). A sensitivity of 40% and a specificity
      of 97.5% was calculated with the receiver operating characteristic curve.
      However, COQ 10 levels did not discriminate between the MSA and PD groups (P =
      0.07). Plasma COQ10 levels were correlated with the severity of motor symptoms
      only in MSA-C patients (b = -0.025, P = 0.009). CONCLUSION: The association
      between decreased COQ10 levels and the severity of motor symptoms in MSA-C
      patients promotes further research. Plasma COQ10 levels alone may not be a
      reliable MSA diagnostic biomarker, and cannot be considered a useful biomarker in
      the differential diagnosis of MSA vs PD.

PMID- 30093365
TI  - How Well Do Incident Reporting Systems Work on Inpatient Psychiatric Units?
AB  - BACKGROUND: Adverse events and medical errors have been shown to be a persistent
      issue in health care. However, little research has been conducted regarding the
      efficacy of incident reporting systems, particularly within an inpatient
      psychiatry setting. METHODS: The medical records from a random sample of 40
      psychiatric units within Veterans Health Administration (VHA) medical centers
      were screened and evaluated by physicians for 9 types of safety events. The
      abstracted safety events were then evaluated to assess if they were caused by an
      error and if they caused harm to the patient. These safety events were then
      matched to incidents that were reported to the VHA Adverse Event Reporting System
      (AERS), which includes all reported adverse events, close calls, and root cause
      analyses that occur within the VHA health system. RESULTS: Overall, 37.4% (95%
      confidence interval [CI] = 33.5%-41.5%) of safety events detected in the medical
      record were reported to the AERS. Among the patient safety events identified, the
      most commonly reported to the AERS were patient falls (52.3%), assaults (46.2%),
      and elopements (42.3%). Reporting rates increased when the patient safety event
      resulted in harm to the patient (48.2%; CI = 41.6%-55.0%). CONCLUSION: The
      majority of patient safety events that occur on VHA inpatient psychiatric units
      do not get reported to the VHA's Adverse Event Reporting System. These findings
      suggest that self-reporting is not a reliable method of tracking patient safety
      events. Future efforts should target the barriers to inpatient psychiatric
      reporting and develop mechanisms to overcome these barriers.

PMID- 30093366
TI  - The HLA-B*51 Allele Is Strongly Associated With Behcet Disease in an Argentinean
      Population.
AB  - OBJECTIVE: To assess the association between the HLA-B*51 allele and Behcet
      Disease (BD) in Argentinean patients. METHODS: We enrolled 34 consecutive
      Argentinean patients with definitive diagnosis of BD between October 2016 and
      March 2017. None of the patients had the HLA-B*51 allele determined at study
      entry. Unrelated controls (n=240) were randomly obtained from the national
      cadaveric donor database. Demographic and clinical features of the patients were
      recorded by attending physicians through a questionnaire. RESULTS: Mean age of
      cases was 42 years old. Nineteen (55.8%) were male, and the mean age at diagnosis
      was 35 years old; twenty (58.8%) were Mestizos, 8 (23.5%) were Caucasian, and 6
      (17.6%) were Amerindians. Thirteen (38.2%) of 34 cases were HLA-B*51 allele
      positive; 11 were heterozygous and 2 homozygous for the allele. Thirty-four
      (14.2%) of 240 controls were positive for the HLA-B*51 allele. The association
      between BD and HLA-B*51 allele was greater than that of control group (OR=3.75;
      p=0.0012). CONCLUSIONS: The HLA-B*51 allele is strongly associated with BD in
      Argentinean patients. Our finding is consistent with previous studies indicating
      that the HLA-B*51 allele is an important susceptibility gene in BD regardless the
      geographical region and ethnicity.

PMID- 30093368
TI  - The Effect of Mobile App Interventions on Influencing Healthy Maternal Behavior
      and Improving Perinatal Health Outcomes: Systematic Review.
AB  - BACKGROUND: Perinatal morbidity and mortality are significant public health
      issues with an enduring impact on the health and well-being of women and their
      families. Millions of pregnant women now download and use mobile applications to
      access, store, and share health information. However, little is known about the
      consequences. An investigation of their impact on perinatal health outcomes is
      particularly topical. OBJECTIVE: To determine the effects of mobile app
      interventions during pregnancy on influencing healthy maternal behavior and
      improving perinatal health outcomes. METHODS: Searches of PubMed, Embase, the
      Cochrane Library, CINAHL, WHO Global Health Library, POPLINE, and CABI Global
      Health were conducted with no date or language restrictions. Randomized and non
      randomized studies were included if they reported perinatal health outcomes of
      interventions targeting pregnant women, using mobile apps compared with other
      communication modalities or with standard care. The primary outcome measure was
      the change in maternal behaviors (as defined by trial authors), by intervention
      goals. Two reviewers independently extracted data using standardized forms.
      RESULTS: Four randomized controlled trials (RCTs) involving 456 participants were
      included. All studies targeted participants in early pregnancy; however, wide
      variation was evident in participant characteristics, intervention, and study
      outcomes measures. Three trials were based in hospital settings, comparing women
      using mobile apps with routine antenatal care. One community-based trial gave all
      participants a device to promote physical activity; the intervention arm was also
      given a mobile app. All studies reported data for the primary outcome measure,
      describing some benefit from the intervention compared with controls. However,
      few statistically significant primary or secondary outcomes were reported. Due to
      insufficient data, the planned meta-analysis and subgroup analyses were not
      performed. CONCLUSIONS: Due to limited numbers, heterogeneity of interventions,
      comparators, and outcome measures, no firm conclusions can be drawn on the
      effects of mobile application interventions during pregnancy on maternal
      knowledge, behavior change, and perinatal health outcomes. As millions of women
      utilize mobile apps during pregnancy, rigorous studies are essential for health
      care and maternity care providers to optimally design, implement, and evaluate
      interventions.

PMID- 30093367
TI  - The Use of Aspirin to Reduce the Risk of Thrombotic Events in Patients With End
      Stage Renal Disease: Protocol for a Randomized Controlled Trial.
AB  - BACKGROUND: End-stage renal disease (ESRD) is the last stage of chronic kidney
      disease, mainly caused by type 2 diabetes mellitus and characterized by an
      increased mortality risk related to cardiovascular disease. Low-dose aspirin
      (acetylsalicylic acid or ASA) seems to effectively prevent cardiovascular events
      in patients with ESRD. However, the number of interventional studies in this
      population remains limited and the mechanisms of aspirin-related bleeding remain
      poorly understood. Aspirin's efficacy and safety may be modified by the presence
      of type 2 diabetes mellitus or platelet hyperreactivity. OBJECTIVE: The overall
      objective of this protocol is to (1) evaluate aspirin's safety and efficacy in
      reducing the risk of thrombotic events in patients with ESRD on hemodialysis and
      (2) examine whether aspirin's efficacy is modified by the presence of type 2
      diabetes mellitus or platelet hyperreactivity. Specifically, the primary
      objective is to compare the 12-month rate of any thrombotic event (cardiac death,
      nonfatal myocardial infarction, nonfatal stroke, arteriovenous fistula
      thrombosis) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding in
      patients treated with aspirin compared to those on placebo. Secondary objectives
      are to test for effect modification of treatment by the presence of type 2
      diabetes mellitus or platelet hyperreactivity and compare the rate of TIMI minor
      bleeding between treatment groups. METHODS: We developed a protocol for a phase 2
      randomized, single-center, placebo-controlled, triple-blind, superiority clinical
      trial to assess the prophylactic efficacy and safety of aspirin in patients with
      ESRD and on hemodialysis. It follows the ethical principles of the Declaration of
      Helsinki of the World Medical Association. A total of 342 participants would be
      enrolled over 12 months at a large dialysis center. Patients will be randomized
      in a 1:1 ratio and stratified by presence of type 2 diabetes mellitus and
      platelet hyperreactivity to receive either oral aspirin (100 mg/d) or placebo for
      a treatment period of 12 months. An intention-to-treat statistical analysis will
      be performed. RESULTS: The randomized clinical trial will be performed after
      approval by the ethical committee of the participating center and registration at
      ClinicalTrials.gov. CONCLUSIONS: We provide a protocol for a randomized
      controlled trial to evaluate the safety and efficacy of treatment with aspirin to
      reduce the risk of thrombotic events. In addition, such a study would further our
      understanding of the mechanism of aspirin-related bleeding and help identify
      subgroups of best-responders and patients with a higher risk of adverse events.
      REGISTERED REPORT IDENTIFIER: RR1-10.2196/10516.

PMID- 30093369
TI  - Evaluating the Diagnostic Accuracy of Reflectance Confocal Microscopy to Diagnose
      Skin Cancer: Protocol for a Prospective, Multicenter Study.
AB  - BACKGROUND: In the United Kingdom, 350,000 patients per year are referred to
      hospital clinics with suspicious moles, and approximately half undergo a biopsy
      to identify the 5%-10% who require further treatment. If cancer cannot be ruled
      out clinically and on the basis of biopsy results, the lesion is surgically
      removed. One type of precancerous mole, called lentigo maligna, is particularly
      challenging to delineate and treat. Reflectance confocal microscopy (VivaScope,
      Caliber Imaging & Diagnostics) is an imaging technique that can supplement
      dermoscopy in identifying whether a clinically suspicious mole is malignant and
      can better assess lentigo maligna margins for excision. It allows clinicians to
      visualize the skin lesion to a depth of 200 microns with subcellular resolution,
      described as quasi-histological, and therefore better guide more accurate
      diagnoses. OBJECTIVE: The aim of this paper is to describe a prospective, single
      blinded, multicenter study to examine patients with clinically suspicious moles
      or lentigo maligna to determine whether confocal microscopy can both reduce the
      number of unnecessary biopsies of moles and more accurately guide the surgical
      excision margins of lentigo maligna. METHODS: This study will prospectively
      recruit adults into the following two cohorts: diagnostic accuracy and margin
      delineation. The diagnostic accuracy cohort will assess people with clinically
      suspicious lesions suspected of being diagnosed with melanoma and having an
      equivocal finding on dermoscopy or persistent clinical suspicion despite normal
      dermoscopy. Diagnostic accuracy will include the sensitivity and specificity of
      VivaScope in comparison with the histological diagnosis as the gold standard for
      patients. The margin delineation cohort will assess the ability of VivaScope to
      accurately delineate the margins of lentigo maligna compared with that of
      dermoscopy alone using margins taken during Mohs micrographic surgery as the gold
      standard. The primary study outcomes will be the diagnostic accuracy of VivaScope
      for the first cohort of patients and margin agreement between VivaScope and the
      final pathology report for the second cohort of patients. RESULTS: Funding for
      this proposed research is being secured. CONCLUSIONS: The outcomes of the
      proposed study will indicate how many biopsies of nonmelanoma lesions, which are
      potentially unnecessary, could be prevented. This would reduce patient anxiety
      and cost to the National Health Service (NHS) in the United Kingdom. Improved
      margin delineation of lentigo maligna could also improve the surgical clearance
      rates and decrease overall cost. The results would demonstrate whether the
      adoption of VivaScope would potentially benefit patients and the NHS. REGISTERED
      REPORT IDENTIFIER: RR1-10.2196/9296.

PMID- 30093370
TI  - Social Media Landscape of the Tertiary Referral Hospitals in China: Observational
      Descriptive Study.
AB  - BACKGROUND: Social media has penetrated all walks of life. Chinese health care
      institutions are increasingly utilizing social media to connect with their
      patients for better health service delivery. Current research has focused heavily
      on the use of social media in developed countries, with few studies exploring its
      usage in the context of developing countries, such as China. Tertiary hospitals
      in China are usually located in city centers, and they serve as medical hubs for
      multiple regions, with comprehensive and specialized medical care being provided.
      These hospitals are assumed to be the pioneers in creating official social media
      accounts to connect with their patients due to the fact that they appear to have
      more resources to support this innovative approach to communication and health
      care education. OBJECTIVE: The objective of our study was to examine China's best
      tertiary hospitals, as recognized by The National Health Commission of the
      People's Republic of China (NHCPRC), and to map out the landscape of current
      social media usage by hospitals when engaging with patients. METHODS: We examined
      the best 705 tertiary hospitals in China by collecting and analyzing data
      regarding their usage of popular Chinese social media apps Sina Weibo and WeChat.
      The specific data included (1) hospital characteristics (ie, time since
      established, number of beds, hospital type, and regions or localities) and (2)
      status of social media usage regarding two of the most popular local social media
      platforms in China (ie, time of initiation, number of followers, and number of
      tweets or posts). We further used a logistic regression model to test the
      association between hospital characteristics and social media adoption. RESULTS:
      Of all, 76.2% (537/705) tertiary referral hospitals have created official
      accounts on either Sina Weibo or WeChat, with the latter being more popular among
      the two. In addition, our study suggests that larger and newer hospitals with
      greater resources are more likely to adopt social media, while hospital type and
      affiliation with universities are not significant predictors of social media
      adoption among hospitals. CONCLUSIONS: Our study demonstrated that hospitals are
      more inclined to use WeChat. The move by hospitals from Sina Weibo to WeChat
      indicates that patients are not satisfied by mere communication and that they now
      place more value on health service delivery. Meanwhile, utilizing social media
      requires comprehensive thinking from the hospital side. Once adopted, hospitals
      are encouraged to implement specific rules regarding social media usage. In the
      future, a long journey still lies ahead for hospitals in terms of operating their
      official social media accounts.

PMID- 30093373
TI  - A Novel Model for Enhanced Prediction and Understanding of Unplanned 30-Day
      Pediatric Readmission.
AB  - OBJECTIVES: To develop a model to assist clinicians in reducing 30-day unplanned
      pediatric readmissions and to enhance understanding of risk factors leading to
      such readmissions. METHODS: Data consisting of 38 143 inpatient clinical
      encounters at a tertiary pediatric hospital were retrieved, and 50% were used for
      training on a multivariate logistic regression model. The pediatric Rothman Index
      (pRI) was 1 of the novel candidate predictors considered. Multivariate model
      selection was conducted by minimization of Akaike Information Criteria. The area
      under the receiver operator characteristic curve (AUC) and values for
      sensitivity, specificity, positive predictive value, relative risk, and accuracy
      were computed on the remaining 50% of the data. RESULTS: The multivariate
      logistic regression model of readmission consists of 7 disease diagnosis groups,
      4 measures of hospital resource use, 3 measures of disease severity and/or
      medical complexities, and 2 variables derived from the pRI. Four of the
      predictors are novel, including history of previous 30-day readmissions within
      last 6 months (P < .001), planned admissions (P < .001), the discharge pRI score
      (P < .001), and indicator of whether the maximum pRI occurred during the last 24
      hours of hospitalization (P = .005). An AUC of 0.79 (0.77-0.80) was obtained on
      the independent test data set. CONCLUSIONS: Our model provides significant
      performance improvements in the prediction of unplanned 30-day pediatric
      readmissions with AUC higher than the LACE readmission model and other general
      unplanned 30-day pediatric readmission models. The model is expected to provide
      an opportunity to capture 39% of readmissions (at a selected operating point) and
      may therefore assist clinicians in reducing avoidable readmissions.

PMID- 30093372
TI  - Using Mobile Apps to Assess and Treat Depression in Hispanic and Latino
      Populations: Fully Remote Randomized Clinical Trial.
AB  - BACKGROUND: Most people with mental health disorders fail to receive timely
      access to adequate care. US Hispanic/Latino individuals are particularly
      underrepresented in mental health care and are historically a very difficult
      population to recruit into clinical trials; however, they have increasing access
      to mobile technology, with over 75% owning a smartphone. This technology has the
      potential to overcome known barriers to accessing and utilizing traditional
      assessment and treatment approaches. OBJECTIVE: This study aimed to compare
      recruitment and engagement in a fully remote trial of individuals with depression
      who either self-identify as Hispanic/Latino or not. A secondary aim was to assess
      treatment outcomes in these individuals using three different self-guided mobile
      apps: iPST (based on evidence-based therapeutic principles from problem-solving
      therapy, PST), Project Evolution (EVO; a cognitive training app based on
      cognitive neuroscience principles), and health tips (a health information app
      that served as an information control). METHODS: We recruited Spanish and English
      speaking participants through social media platforms, internet-based
      advertisements, and traditional fliers in select locations in each state across
      the United States. Assessment and self-guided treatment was conducted on each
      participant's smartphone or tablet. We enrolled 389 Hispanic/Latino and 637 non
      Hispanic/Latino adults with mild to moderate depression as determined by Patient
      Health Questionnaire-9 (PHQ-9) score>=5 or related functional impairment.
      Participants were first asked about their preferences among the three apps and
      then randomized to their top two choices. Outcomes were depressive symptom
      severity (measured using PHQ-9) and functional impairment (assessed with Sheehan
      Disability Scale), collected over 3 months. Engagement in the study was assessed
      based on the number of times participants completed active surveys. RESULTS: We
      screened 4502 participants and enrolled 1040 participants from throughout the
      United States over 6 months, yielding a sample of 348 active users. Long-term
      engagement surfaced as a key issue among Hispanic/Latino participants, who
      dropped from the study 2 weeks earlier than their non-Hispanic/Latino
      counterparts (P<.02). No significant differences were observed for treatment
      outcomes between those identifying as Hispanic/Latino or not. Although depressive
      symptoms improved (beta=-2.66, P=.006) over the treatment course, outcomes did
      not vary by treatment app. CONCLUSIONS: Fully remote mobile-based studies can
      attract a diverse participant pool including people from traditionally
      underserved communities in mental health care and research (here, Hispanic/Latino
      individuals). However, keeping participants engaged in this type of "low-touch"
      research study remains challenging. Hispanic/Latino populations may be less
      willing to use mobile apps for assessing and managing depression. Future research
      endeavors should use a user-centered design to determine the role of mobile apps
      in the assessment and treatment of depression for this population, app features
      they would be interested in using, and strategies for long-term engagement. TRIAL
      REGISTRATION: Clinicaltrials.gov NCT01808976;
      https://clinicaltrials.gov/ct2/show/NCT01808976 (Archived by WebCite at
      http://www.webcitation.org/70xI3ILkz).

PMID- 30093371
TI  - Accuracy of Fitbit Devices: Systematic Review and Narrative Syntheses of
      Quantitative Data.
AB  - BACKGROUND: Although designed as a consumer product to help motivate individuals
      to be physically active, Fitbit activity trackers are becoming increasingly
      popular as measurement tools in physical activity and health promotion research
      and are also commonly used to inform health care decisions. OBJECTIVE: The
      objective of this review was to systematically evaluate and report measurement
      accuracy for Fitbit activity trackers in controlled and free-living settings.
      METHODS: We conducted electronic searches using PubMed, EMBASE, CINAHL, and
      SPORTDiscus databases with a supplementary Google Scholar search. We considered
      original research published in English comparing Fitbit versus a reference- or
      research-standard criterion in healthy adults and those living with any health
      condition or disability. We assessed risk of bias using a modification of the
      Consensus-Based Standards for the Selection of Health Status Measurement
      Instruments. We explored measurement accuracy for steps, energy expenditure,
      sleep, time in activity, and distance using group percentage differences as the
      common rubric for error comparisons. We conducted descriptive analyses for
      frequency of accuracy comparisons within a +/-3% error in controlled and +/-10%
      error in free-living settings and assessed for potential bias of over- or
      underestimation. We secondarily explored how variations in body placement,
      ambulation speed, or type of activity influenced accuracy. RESULTS: We included
      67 studies. Consistent evidence indicated that Fitbit devices were likely to meet
      acceptable accuracy for step count approximately half the time, with a tendency
      to underestimate steps in controlled testing and overestimate steps in free
      living settings. Findings also suggested a greater tendency to provide accurate
      measures for steps during normal or self-paced walking with torso placement,
      during jogging with wrist placement, and during slow or very slow walking with
      ankle placement in adults with no mobility limitations. Consistent evidence
      indicated that Fitbit devices were unlikely to provide accurate measures for
      energy expenditure in any testing condition. Evidence from a few studies also
      suggested that, compared with research-grade accelerometers, Fitbit devices may
      provide similar measures for time in bed and time sleeping, while likely markedly
      overestimating time spent in higher-intensity activities and underestimating
      distance during faster-paced ambulation. However, further accuracy studies are
      warranted. Our point estimations for mean or median percentage error gave equal
      weighting to all accuracy comparisons, possibly misrepresenting the true point
      estimate for measurement bias for some of the testing conditions we examined.
      CONCLUSIONS: Other than for measures of steps in adults with no limitations in
      mobility, discretion should be used when considering the use of Fitbit devices as
      an outcome measurement tool in research or to inform health care decisions, as
      there are seemingly a limited number of situations where the device is likely to
      provide accurate measurement.

PMID- 30093375
TI  - Dementia in Dialysis: An Eye on Best Practices.

PMID- 30093374
TI  - Dementia, Alzheimer's Disease, and Mortality after Hemodialysis Initiation.
AB  - BACKGROUND AND OBJECTIVES: Older patients with ESKD experience rapid declines in
      executive function after initiating hemodialysis; these impairments might lead to
      high rates of dementia and Alzheimer's disease in this population. We estimated
      incidence, risk factors, and sequelae of diagnosis with dementia and Alzheimer's
      disease among older patients with ESKD initiating hemodialysis. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: We studied 356,668 older (age >=66 years old)
      patients on hemodialysis (January 1, 2001 to December 31, 2013) from national
      registry data (US Renal Data System) linked to Medicare. We estimated the risk
      (cumulative incidence) of diagnosis of dementia and Alzheimer's disease and
      studied factors associated with these disorders using competing risks models to
      account for death, change in dialysis modality, and kidney transplant. We
      estimated the risk of subsequent mortality using Cox proportional hazards models.
      RESULTS: The 1- and 5-year risks of diagnosed dementia accounting for competing
      risks were 4.6% and 16% for women, respectively, and 3.7% and 13% for men,
      respectively. The corresponding Alzheimer's disease diagnosis risks were 0.6% and
      2.6% for women, respectively, and 0.4% and 2.0% for men, respectively. The
      strongest independent risk factors for diagnosis of dementia and Alzheimer's
      disease were age >=86 years old (dementia: hazard ratio, 2.11; 95% confidence
      interval, 2.04 to 2.18; Alzheimer's disease: hazard ratio, 2.11; 95% confidence
      interval, 1.97 to 2.25), black race (dementia: hazard ratio, 1.70; 95% confidence
      interval, 1.67 to 1.73; Alzheimer's disease: hazard ratio, 1.78; 95% confidence
      interval, 1.71 to 1.85), women (dementia: hazard ratio, 1.10; 95% confidence
      interval, 1.08 to 1.12; Alzheimer's disease: hazard ratio, 1.12; 95% confidence
      interval, 1.08 to 1.16), and institutionalization (dementia: hazard ratio, 1.36;
      95% confidence interval, 1.33 to 1.39; Alzheimer's disease: hazard ratio, 1.10;
      95% confidence interval, 1.05 to 1.15). Older patients on hemodialysis with a
      diagnosis of dementia were at 2.14-fold (95% confidence interval, 2.07 to 2.22)
      higher risk of subsequent mortality; those with a diagnosis of Alzheimer's
      disease were at 2.01-fold (95% confidence interval, 1.89 to 2.15) higher
      mortality risk. CONCLUSIONS: Older patients on hemodialysis are at substantial
      risk of diagnosis with dementia and Alzheimer's disease, and carrying these
      diagnoses is associated with a twofold higher mortality.

PMID- 30093376
TI  - Influence of rib impact on thoracic gunshot trauma.
AB  - INTRODUCTION: The influence of rib impact on thoracic gunshot trauma remains
      unclear, despite its high occurrence. This study therefore investigates the
      effect of rib impact on a bullet's terminal properties and injury severity.
      METHODS: Two bullets were used: 5.56*45 mm (full charge and reduced charge) and
      7.62*51 mm (full charge). For each bullet, three impact groups were tested: (1)
      plain 10% ballistic gelatin (control) conditioned at 4 degrees C, (2) intercostal
      impact, and (3) rib impact, the latter two tested with samples of porcine
      thoracic walls embedded in gelatin. Analysis included penetration depth,
      trajectory change, yaw, fragmentation, velocity reduction, energy deposition and
      temporary and permanent cavity characteristics. RESULTS: No significant
      differences were observed for most variables. Differences were found between rib
      (and intercostal) impact and the control groups, suggesting that the inclusion of
      thoracic walls produces an effect more significant than the anatomical impact
      site. Effects were ammunition specific. For the 7.62*51 mm round, rib impact
      caused an earlier onset of yaw and more superficial permanent gelatin damage
      compared with plain gelatin. This round also formed a larger temporary cavity on
      rib impact than intercostal impact. Rib (and intercostal impact) created a
      smaller temporary cavity than the control for the 5.56*45 mm round. For the
      reduced-charge 5.56*45 mm round, rib and intercostal impact produced greater
      velocity reduction compared with plain gelatin. CONCLUSIONS: This study provides
      new insights into the role of rib impact in thoracic gunshot injuries, and
      indicates that the effects are ammunition dependent. Unlike the 5.56*45 mm
      rounds, rib impact with the 7.62*51 mm rounds increases the risk of severe
      wounding.

PMID- 30093377
TI  - A mixed methods study of the impact of consultant overnight working in an English
      Emergency Department.
AB  - BACKGROUND: There is a growing expectation that consultant-level doctors should
      be present within an ED overnight. However, there is a lack of robust evidence
      substantiating the impact on patient waiting times, safety or the workforce.
      OBJECTIVES: To evaluate the impact of consultant-level doctors overnight working
      in ED in a large university hospital. METHODS: We conducted a controlled
      interrupted time series analysis to study ED waiting times before and after the
      introduction of consultant night working. Adverse event reports (AER) were used
      as a surrogate for patient safety. We conducted interviews with medical and
      nursing staff to explore attitudes to night work. RESULTS: The reduction seen in
      average time in department relative to the day, following the introduction of
      consultant was non-significant (-12 min; 95% CI -28 to 4, p=0.148). Analysis of
      hourly arrivals and departures indicated that overnight work was inherited from
      the day. There were three (0.9%) moderate and 0 severe AERs in 1 year. The
      workforce reported that night working had a negative impact on sleep patterns,
      performance and well-being and there were mixed views about the benefits of
      consultant night presence. Additional time off during the day acted as
      compensation for night work but resulted in reduced contact with ED teams.
      CONCLUSIONS: Our single-site study was unable to demonstrate a clinically
      important impact of consultant night working on total time patients spend in the
      department. Our analysis suggests there may be more potential to reduce total
      time in department during the day, at our study site. Negative impacts on well
      being, and likely resistance to consultant night working should not be ignored.
      Further studies of night working are recommended to substantiate our results.

PMID- 30093378
TI  - Emergency department provider perspectives on elder abuse and development of a
      novel ED-based multidisciplinary intervention team.
AB  - BACKGROUND: An ED visit provides a unique opportunity to identify elder abuse,
      which is common and has serious medical consequences. Despite this, emergency
      providers rarely recognise or report it. We have begun the design of an ED-based
      multidisciplinary consultation service to improve identification and provide
      comprehensive medical and forensic assessment and treatment for potential
      victims. METHODS: We qualitatively explored provider perspectives to inform
      intervention development. We conducted 15 semistructured focus groups with 101
      providers, including emergency physicians, social workers, nurses, technologists,
      security, radiologists and psychiatrists at a large, urban academic medical
      centre. Focus groups were transcribed, and data were analysed to identify themes.
      RESULTS: Providers reported not routinely assessing for elder mistreatment and
      believed that they commonly missed it. They reported 10 reasons for this,
      including lack of knowledge or training, no time to conduct an evaluation,
      concern that identifying elder abuse would lead to additional work, and absence
      of a standardised response. Providers believed an ED-based consultation service
      would be frequently used and would increase identification, improve care and help
      ensure safety. They made 21 recommendations for a multidisciplinary team,
      including the importance of 24/7 availability, the value of a positive attitude
      in a consulting service and the importance of feedback to referring ED providers.
      Participants also highlighted that geriatric nurse practitioners may have ideal
      clinical and personal care training to contribute to the team. CONCLUSIONS: An ED
      based multidisciplinary consultation service has potential to impact care for
      elder abuse victims. Insights from providers will inform intervention
      development.

PMID- 30093379
TI  - Interventions to improve patient flow in emergency departments: an umbrella
      review.
AB  - OBJECTIVES: Patient flow and crowding are two major issues in ED service
      improvement. A substantial amount of literature exists on the interventions to
      improve patient flow and crowding, making it difficult for policymakers, managers
      and clinicians to be familiar with all the available literature and identify
      which interventions are supported by the evidence. This umbrella review provides
      a comprehensive analysis of the evidence from existing quantitative systematic
      reviews on the interventions that improve patient flow in EDs. METHODS: An
      umbrella review of systematic reviews published between 2000 and 2017 was
      undertaken. Included studies were systematic reviews and meta-analyses of
      quantitative primary studies assessing an intervention that aimed to improve ED
      throughput. RESULTS: The search strategy yielded 623 articles of which 13 were
      included in the umbrella review. The publication dates of the systematic reviews
      ranged from 2006 to 2016. The 13 systematic reviews evaluated 26 interventions:
      full capacity protocols, computerised provider order entry, scribes, streaming,
      fast track and triage. Interventions with similar characteristics were grouped
      together to produce the following categories: diagnostic services,
      assessment/short stay units, nurse-directed interventions, physician-directed
      interventions, administrative/organisational and miscellaneous. The statistical
      evidence from 14 primary randomised controlled trials (RCTs) was evaluated to
      determine if correlation or clustering of observations was considered. Only the
      fast track intervention had moderate evidence to support its use but the RCTs
      that assessed the intervention did not use statistical tests that considered
      correlation. CONCLUSIONS: Overall, the evidence supporting the interventions to
      improve patient flow is weak. Only the fast track intervention had moderate
      evidence to support its use but correlation/clustering was not taken into
      consideration in the RCTs examining the intervention. Failure to consider the
      correlation of the data in the primary studies could result in erroneous
      conclusions of effectiveness.

PMID- 30093381
TI  - CASIN the joint: immune aging at the stem cell level.

PMID- 30093380
TI  - Prevalence of anaphylaxis among adults admitted to critical care for severe
      asthma exacerbation.
AB  - BACKGROUND: In asthmatics, making a diagnosis of anaphylaxis could be challenging
      as respiratory symptoms are a common feature of both conditions. Identifying
      anaphylaxis is important to providing appropriate care. A prior study showed that
      anaphylaxis is sometimes misdiagnosed as acute asthma in children. We sought to
      identify the percentage of adults admitted to the intensive care unit (ICU) with
      asthma exacerbations who met criteria for anaphylaxis. METHODS: Retrospective
      chart review of adults admitted with acute asthma to the ICU at Jacobi Medical
      Center, a Level 1 trauma centre in Bronx, New York. Study period was January 2012
      to December 2014. Using the criteria outlined in the World Allergy Organization's
      Anaphylaxis Guidelines, we identified patients who met criteria for anaphylaxis.
      RESULTS: 105 patients were identified: 17 were excluded because their main
      reason(s) for admission was not asthma. 7 (8%) of the 88 cases eligible for the
      study met diagnostic criteria for anaphylaxis while 3 (3.4%) were highly likely
      to have had anaphylaxis. The baseline characteristics of the seven patients were
      similar to that of the overall population studied. They however had shorter onset
      of symptoms (median (IQR): 3.5 (2-6) vs 24 hours (12-72), p<0.001), were more
      likely to have been intubated (71%vs31%, p=0.04), received intramuscular
      epinephrine by the emergency medical services or in the emergency room (86%vs42%,
      p=0.04) and received antihistamines (28.6%vs1.2%, p=0.02). None of these seven
      patients died. Only one of the seven patients was prescribed an epinephrine pen
      injector and referred to an allergist at discharge. CONCLUSION: In this single
      centre retrospective review, 3.4% of adults admitted to the ICU for acute severe
      asthma also met criteria for anaphylaxis.

PMID- 30093382
TI  - Detailing the genomic landscape of myeloma.

PMID- 30093383
TI  - TPO-logy accepted.

PMID- 30093384
TI  - Endosome trafficking: blood and more.

PMID- 30093385
TI  - Rasburicase-induced hemolytic anemia in previously undiagnosed G6PD deficiency.

PMID- 30093387
TI  - Elucidation of near-resonance vibronic coherence lifetimes by nonadiabatic
      electronic-vibrational state character mixing.
AB  - Recent work suggests that the long-lived coherences observed in both natural and
      artificial light-harvesting systems (such as the Fenna-Matthews-Olson complex)
      could be attributed to the mixing of the pigments' electronic and vibrational
      degrees of freedom. To investigate the underlying mechanism of these long
      coherence lifetimes, a sophisticated description of interactions between the
      molecular aggregates and the nonequilibrium fluctuations in the surrounding
      environment is necessary. This is done by implementing the hierarchical equations
      of motion approach on model homodimers, a method used in the intermediate
      coupling regime for many molecular aggregates wherein the nonequilibrium
      environment phonons play nontrivial roles in exciton dynamics. Here we report a
      character change in the vibronic states-reflective of property mixing between the
      electronic and vibrational states-induced by an interplay between system coupling
      parameters within the exciton-vibrational near-resonance regime. This mixing
      dictates vital aspects of coherence lifetime; by tracking the degree of mixing,
      we are able to elucidate the relationship between coherence lifetime and both the
      electronic energy fluctuation and the vibrational relaxation dephasing pathways.

PMID- 30093386
TI  - Directionally biased sidestepping of Kip3/kinesin-8 is regulated by ATP waiting
      time and motor-microtubule interaction strength.
AB  - Kinesin-8 motors, which move in a highly processive manner toward microtubule
      plus ends where they act as depolymerases, are essential regulators of
      microtubule dynamics in cells. To understand their navigation strategy on the
      microtubule lattice, we studied the 3D motion of single yeast kinesin-8 motors,
      Kip3, on freely suspended microtubules in vitro. We observed short-pitch, left
      handed helical trajectories indicating that kinesin-8 motors frequently switch
      protofilaments in a directionally biased manner. Intriguingly, sidestepping was
      not directly coupled to forward stepping but rather depended on the average dwell
      time per forward step under limiting ATP concentrations. Based on our
      experimental findings and numerical simulations we propose that effective
      sidestepping toward the left is regulated by a bifurcation in the Kip3 step
      cycle, involving a transition from a two-head-bound to a one-head-bound
      conformation in the ATP-waiting state. Results from a kinesin-1 mutant with
      extended neck linker hint toward a generic sidestepping mechanism for processive
      kinesins, facilitating the circumvention of intracellular obstacles on the
      microtubule surface.

PMID- 30093388
TI  - Breakdown of the Wiedemann-Franz law in a unitary Fermi gas.
AB  - We report on coupled heat and particle transport measurements through a quantum
      point contact (QPC) connecting two reservoirs of resonantly interacting, finite
      temperature Fermi gases. After heating one of them, we observe a particle current
      flowing from cold to hot. We monitor the temperature evolution of the reservoirs
      and find that the system evolves after an initial response into a nonequilibrium
      steady state with finite temperature and chemical potential differences across
      the QPC. In this state any relaxation in the form of heat and particle currents
      vanishes. From our measurements we extract the transport coefficients of the QPC
      and deduce a Lorenz number violating the Wiedemann-Franz law by one order of
      magnitude, a characteristic persisting even for a wide contact. In contrast, the
      Seebeck coefficient takes a value close to that expected for a noninteracting
      Fermi gas and shows a smooth decrease as the atom density close to the QPC is
      increased beyond the superfluid transition. Our work represents a fermionic
      analog of the fountain effect observed with superfluid helium and poses
      challenges for microscopic modeling of the finite temperature dynamics of the
      unitary Fermi gas.

PMID- 30093389
TI  - Sticking and stacking: Persistent ordering of fragmented DNA analogs.

PMID- 30093392
TI  - Rapid Direct Susceptibility Testing from Positive Blood Cultures by the Matrix
      Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry-Based
      Direct-on-Target Microdroplet Growth Assay.
AB  - The recently developed direct-on-target microdroplet growth assay (DOT-MGA)
      allows rapid universal antimicrobial susceptibility testing (AST) using matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF
      MS). Here, we investigated a direct application of this method on positive blood
      cultures (BCs) for the acceleration of sepsis diagnostics. Blood samples spiked
      with meropenem-nonsusceptible and meropenem-susceptible Enterobacterales isolates
      were inoculated into Bactec Plus Aerobic/F bottles and incubated in the Bactec
      automated system. Positive-BC broth was processed using four different methods,
      filtration/dilution, dilution, lysis/centrifugation, and differential
      centrifugation. For both dilution-based methods, AST was performed from 1:100,
      1:1,000, and 1:10,000 dilutions of positive-BC broth in cation-adjusted Mueller
      Hinton broth (CA-MHB). For both centrifugation-based methods, a 0.5 McFarland
      standard turbidity suspension was prepared from a bacterial pellet and adjusted
      to a final inoculum of 5 * 105 CFU/ml in CA-MHB. Six-microliter microdroplets
      with or without meropenem at the breakpoint concentration were spotted in
      triplicate onto a MALDI-TOF MS target, followed by incubation in a humidity
      chamber for 3 or 4 h and subsequent broth removal. Spectra were evaluated by
      MALDI Biotyper software. The test was considered valid if the growth control
      without antibiotic achieved an identification score of >=1.7. For samples with
      meropenem, successful identification (score, >=1.7) was interpreted as a
      nonsusceptible result, whereas failed identification (score, <1.7) defined
      susceptibility. The best test performance was achieved with the
      lysis/centrifugation method after a 4-h incubation. At this time point, 96.3%
      validity, 91.7% sensitivity, and 100% specificity were reached. This study
      demonstrated the feasibility and accuracy of a rapid DOT-MGA from positive BCs.
      Parallel to susceptibility determination, this method provides simultaneous
      species identification.

PMID- 30093390
TI  - Squeezing cells through the epigenetic machinery.

PMID- 30093391
TI  - Comparison of the Sensititre YeastOne and CLSI M38-A2 Microdilution Methods in
      Determining the Activity of Amphotericin B, Itraconazole, Voriconazole, and
      Posaconazole against Aspergillus Species.
AB  - This study compared the YeastOne and reference CLSI M38-A2 broth microdilution
      methods for antifungal susceptibility testing of Aspergillus species. The MICs of
      antifungal agents were determined for 100 Aspergillus isolates, including 54
      Aspergillus fumigatus (24 TR34/L98H isolates), 23 A. flavus, 13 A. terreus, and
      10 A. niger isolates. The overall agreement (within 2 2-fold dilutions) between
      the two methods was 100%, 95%, 92%, and 90% for voriconazole, posaconazole,
      itraconazole, and amphotericin B, respectively. The voriconazole geometric mean
      (GM) MICs were nearly identical for all isolates using both methods, whereas the
      itraconazole and posaconazole GM MICs obtained using the YeastOne method were
      approximately 1 dilution lower than those obtained using the reference method. In
      contrast, the amphotericin B GM MIC obtained using the YeastOne method was 3.3
      fold higher than that observed using the reference method. For the 24 A.
      fumigatus TR34/L98H isolates assayed, the categorical agreement (classified
      according to the CLSI epidemiological cutoff values) was 100%, 87.5%, and 83.3%
      for itraconazole, voriconazole, and posaconazole, respectively. For four A. niger
      isolates, the itraconazole MICs were >8 MUg/ml using the M38-A2 method due to
      trailing growth, whereas the corresponding itraconazole MICs obtained using the
      YeastOne method were all <=0.25 MUg/ml without trailing growth. These data
      suggest that the YeastOne method can be used as an alternative for azole
      susceptibility testing of Aspergillus species and for detecting the A. fumigatus
      TR34/L98H isolates but that this method fails to detect A. niger isolates
      exhibiting trailing growth with itraconazole. Additionally, for isolates with
      azole MICs that approach or that are at susceptibility breakpoints or with high
      amphotericin B MICs detected using the YeastOne method, further MIC confirmation
      using the reference CLSI method is needed.

PMID- 30093393
TI  - Diagnostic Performance of Multiplex Nucleic Acid Testing of Bronchoalveolar
      Lavage and Bronchial Wash Specimens for Respiratory Viral Pathogens.
AB  - There is limited knowledge on the yield of performing multiplex nucleic acid
      testing (NAT) on multiple lower respiratory tract specimens from a single patient
      with a single instance of infection. We evaluated the performance characteristics
      of multiplex NAT assays performed concurrently on bronchoalveolar lavage (BAL)
      and bronchial wash (BW) specimens to detect respiratory pathogens. A
      retrospective study of admitted patients from March 2013 through December 2016
      was performed. Individual performance characteristics of BAL and BW specimens
      were compared to positive results from either set of specimens. Only
      contemporaneous BAL and BW specimens (received by the laboratory within 4 h of
      each other) were included. The final cohort included 170 patients, with 184
      contemporaneous BAL and BW specimens submitted for multiplex NAT (median age, 58
      years; 62% male). Of the patients with positive NAT results, 38 of 40 BW
      specimens tested positive (overall percent agreement with combined testing,
      98.9%; 95% confidence interval [CI], 95.5 to 98.9%), and 34 of 40 BAL specimens
      tested positive (overall percent agreement with combined testing, 96.7%; 95% CI,
      93.0 to 96.7%). Assays performed on BW specimens identified 4 additional
      specimens and had a higher positive percent agreement (95.0%) with combined
      testing results compared to those performed on BAL specimens (85.0%). There was
      exact concordance in 174 specimens (94.6%; negative and positive for respiratory
      pathogens, 144 and 34 specimens, respectively). We observed high concordance
      (95%) between multiplex NAT results from contemporaneous BAL and BW specimens.
      Performance characteristics of BW specimen testing were equivalent to those of
      BAL specimen testing. The benefit of performing additional testing should be
      carefully considered against the potential complications and health care costs.

PMID- 30093394
TI  - BmGPAC, an Antigen Capture Assay for Detection of Active Babesia microti
      Infection.
AB  - Human babesiosis is an emerging zoonotic infectious disease caused by
      intraerythrocytic protozoan parasites of the genus Babesia Most cases of human
      babesiosis are caused by Babesia microti and often manifest in individuals over
      the age of 50 years or in patients with a compromised immune system. Patients who
      develop symptomatic B. microti infections usually experience months of
      asymptomatic infection after the acute infection has resolved. About one-fifth of
      B. microti-infected adults never develop symptoms. These asymptomatically
      infected individuals sometimes donate blood and thus can transmit B. microti
      through blood transfusion. Current assays for detection of active B. microti
      infections can be used to screen donor blood prior to transfusion, but they rely
      primarily on microscopy or PCR methods, which have sensitivity and technical
      limitations. Here we report the development of an antigen capture enzyme-linked
      immunosorbent assay (BmGPAC) based on a major secreted immunodominant antigen of
      B. microti (BmGPI12/BmSA1), and we provide evidence that this assay is superior
      for detection of active B. microti infections, compared to available microscopy
      methods and serological assays. The assay has been evaluated using supernatants
      of B. microti-infected erythrocytes cultured in vitro, sera from B. microti
      infected laboratory mice, and sera from wild mice and human patients. Our data
      suggest that the BmGPAC assay is a reliable assay for detection of active B.
      microti infections and is superior to real-time PCR and antibody assays for
      diagnosis of acute B. microti infections, screening of the blood supply, and
      epidemiological surveys of humans and animal reservoir hosts.

PMID- 30093395
TI  - A double Philadelphia chromosome-positive chronic myeloid leukemia patient, co
      expressing P210BCR-ABL1 and P195BCR-ABL1 isoforms.

PMID- 30093396
TI  - ASXL2 regulates hematopoiesis in mice and its deficiency promotes myeloid
      expansion.
AB  - Chromosomal translocation t(8;21)(q22;q22) which leads to generation of oncogenic
      RUNX1-RUNX1T1 (AML1-ETO) fusion is observed in about 10% of acute myelogenous
      leukemia (AML). To uncover somatic mutations that cooperate with t(8;21)-driven
      leukemia, we performed whole and targeted exome sequencing of an Asian cohort at
      diagnosis and relapse. We identified high frequency of truncating alterations in
      ASXL2 along with recurrent mutations of KIT, TET2, MGA, FLT3, and DHX15 in this
      subtype of AML. To investigate in-depth the role of ASXL2 in normal
      hematopoiesis, we utilized a mouse model of ASXL2 deficiency. Loss of ASXL2
      caused progressive hematopoietic defects characterized by myeloid hyperplasia,
      splenomegaly, extramedullary hematopoiesis and poor reconstitution ability in
      transplantation models. Parallel analyses of young and >1-year old Asxl2
      deficient mice revealed age-dependent perturbations affecting not only myeloid
      and erythroid differentiation but also maturation of lymphoid cells. Overall,
      these findings establish a critical role of ASXL2 in maintaining steady state
      hematopoiesis and provide insights into how its loss primes expansion of myeloid
      cells.

PMID- 30093397
TI  - The homeobox transcription factor HB9 induces senescence and blocks
      differentiation in hematopoietic stem and progenitor cells.
AB  - The homeobox gene HLXB9 encodes for the transcription factor HB9, which is
      essential for pancreatic as well as motor neuronal development. Beside its
      physiologic expression pattern, aberrant HB9 expression has been observed in
      several neoplasias. Especially in infant translocation t(7;12) acute myeloid
      leukemia aberrant HB9 expression is the only known molecular hallmark and assumed
      to be a key factor in leukemic transformation. However, up to now only poor
      functional data exist addressing the oncogenic potential of HB9 or its influence
      on hematopoiesis. We investigated the influence of HB9 on cell proliferation and
      cell cycle in vitro, as well as on hematopoietic stem cell differentiation in
      vivo using murine and human model systems. In vitro, HB9 expression led to
      premature senescence in human HT1080 and murine NIH3T3 cells, providing for the
      first time evidence for an oncogenic potential of HB9. Onset of senescence was
      characterized by induction of the p53-p21 tumor suppressor network, resulting in
      growth arrest, accompanied by morphological transformation and expression of
      senescence-associated beta-galactosidase. In vivo, HB9-transduced primary murine
      hematopoietic stem and progenitor cells underwent a profound differentiation
      arrest and accumulated at the megakaryocyte/erythrocyte progenitor stage. In
      line, gene expression analyses revealed de novo expression of erythropoiesis
      related genes in human CD34+ hematopoietic stem and progenitor cells upon HB9
      expression. In summary, the novel findings of HB9 dependent premature senescence
      and myeloid-biased perturbed hematopoietic differentiation shed light on the
      oncogenic properties of HB9 in translocation t(7;12) acute myeloid leukemia for
      the first time.

PMID- 30093398
TI  - Incidence, outcomes, and risk factors of pleural effusion in patients receiving
      dasatinib therapy for Philadelphia chromosome-positive leukemia.
AB  - Dasatinib, a second-generation BCR-ABL1 tyrosine kinase inhibitor, is approved
      for the treatment of chronic myeloid leukemia and Philadelphia chromosome
      positive acute lymphoblastic leukemia, both as first-line therapy and after
      imatinib intolerance or resistance. While generally well tolerated, dasatinib has
      been associated with a higher risk for pleural effusions. Frequency, risk
      factors, and outcomes associated with pleural effusion were assessed in two phase
      3 trials (DASISION and 034/Dose-optimization) and a pooled population of 11
      trials that evaluated patients with chronic myeloid leukemia and Philadelphia
      chromosome-positive acute lymphoblastic leukemia treated with dasatinib
      (including DASISION and 034/Dose-optimization). In this largest assessment of
      patients across the dasatinib clinical trial program (N=2712), pleural effusion
      developed in 6% to 9% of patients at risk annually in DASISION, and in 5% to 15%
      of patients at risk annually in 034/Dose-optimization. With a minimum follow-up
      of 5 and 7 years, drug-related pleural effusion occurred in 28% of patients in
      DASISION and in 33% of patients in 034/Dose-optimization, respectively. A
      significant risk factor identified for developing pleural effusion by a
      multivariate analysis was age. We found that overall responses to dasatinib,
      progression-free survival, and overall survival were similar in patients who
      developed pleural effusion and in patients who did not.

PMID- 30093399
TI  - Novel deep targeted sequencing method for minimal residual disease monitoring in
      acute myeloid leukemia.
AB  - A high proportion of patients with acute myeloid leukemia who achieve minimal
      residual disease (MRD) negative status ultimately relapse because a fraction of
      pathological clones remains undetected by standard methods. We designed and
      validated a high-throughput sequencing method for MRD assessment of cell
      clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-SNVs. For clinical
      validation, 106 follow-up samples from 63 patients in complete remission were
      studied by NGS, evaluating the level of mutations detected at diagnosis. The
      predictive value of MRD status by NGS, multiparameter flow cytometry, or
      quantitative PCR was determined by survival analysis. The method achieved a
      sensitivity of 10-4 for SNV mutations and 10-5 for insertions/deletions and could
      be used in acute myeloid leukemia patients who carry any mutation (86% in our
      diagnosis data set). NGS-determined MRD positive status was associated with lower
      disease-free survival (hazard ratio [HR] 3.4, p=0.005) and lower overall survival
      (HR 4.2, p<0.001). Multivariate analysis showed that MRD positive status by NGS
      was an independent factor associated with risk of death (HR 4.54, p =0.005) and
      the only independent factor conferring risk of relapse (HR 3.76, p =0.012). This
      NGS based method simplifies and standardizes MRD evaluation, with high
      applicability in acute myeloid leukemia. It also improves upon flow cytometry and
      quantitative PCR to predict acute myeloid leukemia outcome and could be
      incorporated in clinical settings and clinical trials.

PMID- 30093400
TI  - Optimizing Diagnostic Biomarkers of Iron Deficiency Anaemia in Community Dwelling
      Indian Women and Preschool Children.
AB  - The detection of iron deficiency anaemia is challenged by the paucity of
      diagnostic tests demonstrating high sensitivity and specificity. Using two
      biomarkers zinc-protoporphyrin/heme and hepcidin, we established the diagnostic
      cut-off values for iron deficiency anaemia in preschool children and women. We
      randomly selected non-anaemic individuals (n=190; women=90, children=100) and
      individuals with iron deficiency anaemia (n=200; women=100, children=100) from a
      preexisting cohort of healthy preschool children and their mothers. The
      diagnostic performance of these biomarkers was estimated by analyzing receiver
      operating characteristic curves. Diagnostic cut-off's with a high predictive
      value for iron deficiency anaemia were selected. Median zinc-protoporphyrin/heme
      and hepcidin values in non-anaemic children were 49MUmol/mol heme and 42ng/mL
      respectively and in non-anaemic women were 66MUmol/mol heme and 17.7ng/mL
      respectively. Children and women with iron deficiency anaemia had higher zinc
      protoporphyrin/heme ratios (children=151MUmol/mol heme and women=155MUmol/mol
      heme) and lower hepcidin levels (children=1.2ng/mL and women=0.6ng/mL). A zinc
      protoporphyrin/heme ratio cut-off >90micromole/mole heme in children and
      >107micromole/mole heme in women was associated with a high diagnostic likelihood
      for iron deficiency anaemia (children, likelihood ratio=20.3: women, likelihood
      ratio=10.8). Hepcidin cut-off values of <=6.8ng/mL in children and <=4.5ng/mL in
      women were associated with a high diagnostic likelihood for iron deficiency
      anaemia (children, likelihood ratio=14.3: women, likelihood ratio=16.2). The
      reference ranges and cut-off values identified in this study provide clinicians
      with guidance for applying these tests to detect iron deficiency anaemia.
      Erythrocyte zinc-protoporphyrin/heme ratio is a valid point-of-care biomarker to
      diagnose iron deficiency anaemia.

PMID- 30093401
TI  - Gemtuzumab Ozogamicin in children with relapsed or refractory acute myeloid
      leukemia: a report of Berlin-Frankfurt-Munster study group.
AB  - Despite intensified salvage treatments, children with relapsed/refractory acute
      myeloid leukemia have poor survival. We evaluated Gemtuzumab Ozogamicin (CD33
      targeted drug) used on compassionate basis in patients diagnosed from 1995 until
      2014 within Acute Myeloid Leukemia-Berlin-Frankfurt-Munster studies and
      identified 76 patients (<18 years) with highly-advanced and pretreated acute
      myeloid leukemia [refractory de novo acute myeloid leukemia (n=10), de novo acute
      myeloid leukemia refractory to relapse (1st early: n=41; 1st late: n=10; 2nd or
      more: n=10), and secondary acute myeloid leukemia (n=5)]. At doses of 2.5-10
      mg/m,2, Gemtuzumab Ozogamicin was administered in 1-4 cycles as single agent
      (47%), combined with cytarabine (47%), or others (6%). Most common grade 3/4
      adverse events were infections or febrile neutropenia (78% of severe adverse
      events), infusion-related immunologic reactions (6%), and gastrointestinal
      symptoms (5%). Three patients experienced veno-occlusive disease (one fatal due
      to exacerbation of a preexisting cardiomyopathy). Sixty-four percent received
      subsequent hematopoietic stem cell transplantation. Probability of 4-year overall
      survival was 18+/-5% in all, 27+/-7% in patients with and 0% in patients without
      hematopoietic stem cell transplantation (p<0.0001). Administration of Gemtuzumab
      Ozogamicin on a patient-specific, compassionate use basis was frequently
      considered in our study group and proved to be effective for bridging children
      with very advanced AML to hematopoietic stem cell transplantation. Uniform
      prospective studies for these patients are urgently needed.

PMID- 30093402
TI  - Molecular profiling reveals immunogenic cues in anaplastic large cell lymphomas
      with DUSP22 rearrangements.
AB  - Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin
      lymphomas broadly segregated into ALK-positive and ALK-negative types. Although
      ALK-positive ALCLs consistently bear rearrangements of the ALK tyrosine kinase
      gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30%
      of ALK-negative ALCLs have rearrangements of DUSP22 and have excellent long-term
      outcomes with standard therapy. To better understand this group of tumors, we
      evaluated their molecular signature using gene expression profiling. DUSP22
      rearranged ALCLs belonged to a distinct subset of ALCLs that lacked expression of
      genes associated with JAK-STAT3 signaling, a pathway contributing to growth in
      the majority of ALCLs. Reverse-phase protein array and immunohistochemical
      studies confirmed the lack of activated STAT3 in DUSP22-rearranged ALCLs. DUSP22
      rearranged ALCLs also overexpressed immunogenic cancer-testis antigen (CTA) genes
      and showed marked DNA hypomethylation by reduced representation bisulfate
      sequencing and DNA methylation arrays. Pharmacologic DNA demethylation in ALCL
      cells recapitulated the overexpression of CTAs and other DUSP22 signature genes.
      In addition, DUSP22-rearranged ALCLs minimally expressed PD-L1 compared with
      other ALCLs, but showed high expression of the costimulatory gene CD58 and HLA
      class II. Taken together, these findings indicate that DUSP22 rearrangements
      define a molecularly distinct subgroup of ALCLs, and that immunogenic cues
      related to antigenicity, costimulatory molecule expression, and inactivity of the
      PD-1/PD-L1 immune checkpoint likely contribute to their favorable prognosis. More
      aggressive ALCLs might be pharmacologically reprogrammed to a DUSP22-like
      immunogenic molecular signature through the use of demethylating agents and/or
      immune checkpoint inhibitors.

PMID- 30093404
TI  - Arginine 107 of yeast ATP synthase subunit g mediates sensitivity of the
      mitochondrial permeability transition to phenylglyoxal.
AB  - Modification with arginine-specific glyoxals modulates the permeability
      transition (PT) of rat liver mitochondria, with inhibitory or inducing effects
      that depend on the net charge of the adduct(s). Here, we show that phenylglyoxal
      (PGO) affects the PT in a species-specific manner (inhibition in mouse and yeast,
      induction in human and Drosophila mitochondria). Following the hypotheses (i)
      that the effects are mediated by conserved arginine(s) and (ii) that the PT is
      mediated by the F-ATP synthase, we have narrowed the search to 60 arginines. Most
      of these residues are located in subunits alpha, beta, gamma, epsilon, a, and c
      and were excluded because PGO modification did not significantly affect enzyme
      catalysis. On the other hand, yeast mitochondria lacking subunit g or bearing a
      subunit g R107A mutation were totally resistant to PT inhibition by PGO. Thus,
      the effect of PGO on the PT is specifically mediated by Arg-107, the only subunit
      g arginine that has been conserved across species. These findings are evidence
      that the PT is mediated by F-ATP synthase.

PMID- 30093403
TI  - AIF promotes a JNK1-mediated cadherin switch independently of respiratory chain
      stabilization.
AB  - Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein occasionally
      involved in cell death that primarily regulates mitochondrial energy metabolism
      under normal cellular conditions. AIF catalyzes the oxidation of NADH in vitro,
      yet the significance of this redox activity in cells remains unclear. Here, we
      show that through its enzymatic activity AIF is a critical factor for oxidative
      stress-induced activation of the mitogen-activated protein kinases JNK1 (c-Jun N
      terminal kinase), p38, and ERK (extracellular signal-regulated kinase). AIF
      dependent JNK1 signaling culminates in the cadherin switch, and genetic reversal
      of this switch leads to apoptosis when AIF is suppressed. Notably, this
      widespread ability of AIF to promote JNK signaling can be uncoupled from its more
      limited role in respiratory chain stabilization. Thus, AIF is a transmitter of
      extra-mitochondrial signaling cues with important implications for human
      development and disease.

PMID- 30093405
TI  - Pharmacological induction of heat shock proteins ameliorates toxicity of mutant
      PKCgamma in spinocerebellar ataxia type 14.
AB  - Amyloid and amyloid-like protein aggregations are hallmarks of multiple, varied
      neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. We
      previously reported that spinocerebellar ataxia type 14 (SCA14), a dominant
      inherited neurodegenerative disease that affects cerebellar Purkinje cells, is
      characterized by the intracellular formation of neurotoxic amyloid-like
      aggregates of genetic variants of protein kinase Cgamma (PKCgamma). A number of
      protein chaperones, including heat shock protein 70 (Hsp70), promote the
      degradation and/or refolding of misfolded proteins and thereby prevent their
      aggregation. Here, we report that, in various SCA14-associated, aggregating
      PKCgamma variants, endogenous Hsp70 is incorporated into aggregates and that
      expression of these PKCgamma mutants up-regulates Hsp70 expression. We observed
      that PKCgamma binds Hsp70 and that this interaction is enhanced in the SCA14
      associated variants, mediated by the kinase domain that is involved in amyloid
      like fibril formation as well as the C2 domain of PKCgamma. Pharmacological up
      regulation of Hsp70 by the Hsp90 inhibitors celastrol and herbimycin A attenuated
      the aggregation of mutant PKCgamma in primary cultured Purkinje cells. Up
      regulation of Hsp70 diminished net PKCgamma aggregation by preventing aggregate
      formation, resulting in decreased levels of apoptotic cell death among primary
      cultured Purkinje cells expressing the PKCgamma variant. Of note, herbimycin A
      also ameliorated abnormal dendritic development. Extending our in vitro
      observations, administration of celastrol to mice up-regulated cerebellar Hsp70.
      Our findings identify heat shock proteins as important endogenous regulators of
      pathophysiological PKCgamma aggregation and point to Hsp90 inhibition as a
      potential therapeutic strategy in the treatment of SCA14.

PMID- 30093407
TI  - Structural insight into proline cis/trans isomerization of unfolded proteins
      catalyzed by the trigger factor chaperone.
AB  - Molecular chaperones often possess functional modules that are specialized in
      assisting the formation of specific structural elements, such as a disulfide
      bridges and peptidyl-prolyl bonds in cis form, in the client protein. A ribosome
      associated molecular chaperone trigger factor (TF), which has a peptidyl-prolyl
      cis/trans isomerase (PPIase) domain, acts as a highly efficient catalyst in the
      folding process limited by peptidyl-prolyl isomerization. Herein we report a
      study on the mechanism through which TF recognizes the proline residue in the
      unfolded client protein during the cis/trans isomerization process. The solution
      structure of TF in complex with the client protein showed that TF recognizes the
      proline-aromatic motif located in the hydrophobic stretch of the unfolded client
      protein through its conserved hydrophobic cleft, which suggests that TF
      preferentially accelerates the isomerization of the peptidyl-prolyl bond that is
      eventually folded into the core of the protein in its native fold. Molecular
      dynamics simulation revealed that TF exploits the backbone amide group of Ile195
      to form an intermolecular hydrogen bond with the carbonyl oxygen of the amino
      acid residue preceding the proline residue at the transition state, which
      presumably stabilizes the transition state and thus accelerates the
      isomerization. The importance of such intermolecular hydrogen-bond formation
      during the catalysis was further corroborated by the activity assay and NMR
      relaxation analysis.

PMID- 30093406
TI  - 14-3-3gamma binds regulator of G protein signaling 14 (RGS14) at distinct sites
      to inhibit the RGS14:Galphai-AlF4- signaling complex and RGS14 nuclear
      localization.
AB  - Regulator of G protein signaling 14 (RGS14) is a multifunctional brain
      scaffolding protein that integrates G protein and Ras/ERK signaling pathways. It
      is also a nucleocytoplasmic shuttling protein. RGS14 binds active Galphai/o via
      its RGS domain, Raf and active H-Ras-GTP via its R1 Ras-binding domain (RBD), and
      inactive Galphai1/3 via its G protein regulatory (GPR) domain. RGS14 suppresses
      long-term potentiation (LTP) in the CA2 region of the hippocampus, thereby
      regulating hippocampally based learning and memory. The 14-3-3 family of proteins
      is necessary for hippocampal LTP and associative learning and memory. Here, we
      show direct interaction between RGS14 and 14-3-3gamma at two distinct sties, one
      phosphorylation-independent and the other phosphorylation-dependent at Ser-218
      that is markedly potentiated by signaling downstream of active H-Ras. Using
      bioluminescence resonance energy transfer (BRET), we show that the pSer-218
      dependent RGS14/14-3-3gamma interaction inhibits active Galphai1-AlF4- binding to
      the RGS domain of RGS14 but has no effect on active H-Ras and inactive Galphai1
      GDP binding to RGS14. By contrast, the phosphorylation-independent binding of 14
      3-3 has no effect on RGS14/Galphai interactions but, instead, inhibits (directly
      or indirectly) RGS14 nuclear import and nucleocytoplasmic shuttling. Together,
      our findings describe a novel mechanism of negative regulation of RGS14
      functions, specifically interactions with active Galphai and nuclear import,
      while leaving the function of other RGS14 domains intact. Ongoing studies will
      further elucidate the physiological function of this interaction between RGS14
      and 14-3-3gamma, providing insight into the functions of both RGS14 and 14-3-3 in
      their roles in modulating synaptic plasticity in the hippocampus.

PMID- 30093408
TI  - IL-1R signaling promotes STAT3 and NF-kappaB factor recruitment to distal cis
      regulatory elements that regulate Il17a/f transcription.
AB  - Interleukin (IL)-1beta plays a critical role in IL-6beta- and transforming growth
      factor beta (TGFbeta)-initiated Th17 differentiation and induction of Th17
      mediated autoimmunity. However, the means by which IL-1 regulates various aspects
      of Th17 development remain poorly understood. We recently reported that IL-1beta
      enhances STAT3 phosphorylation via NF-kappaB-mediated repression of SOCS3 to
      facilitate Il17 transcription and Th17 differentiation, identifying an effect of
      IL-1 signaling on proximal events of STAT3 signaling. Here, we show that IL-1beta
      promotes STAT3 binding to key cis-elements that control IL-17 expression.
      Additionally, we demonstrate that the IL-1-induced NF-kappaB factor RelA directly
      regulates the Il17a/f loci in cooperation with STAT3. Our findings reveal that IL
      1 impacts both proximal signaling events and downstream interactions between
      transcription factors and cis-regulatory elements to promote Il17a/f
      transcription and Th17 differentiation.

PMID- 30093409
TI  - Bacterially expressed HIV-1 gp120 outer-domain fragment immunogens with improved
      stability and affinity for CD4-binding site neutralizing antibodies.
AB  - Protein minimization is an attractive approach for designing vaccines against
      rapidly evolving pathogens such as human immunodeficiency virus, type 1 (HIV-1),
      because it can help in focusing the immune response toward conserved
      conformational epitopes present on complex targets. The outer domain (OD) of HIV
      1 gp120 contains epitopes for a large number of neutralizing antibodies and
      therefore is a primary target for structure-based vaccine design. We have
      previously designed a bacterially expressed outer-domain immunogen (ODEC) that
      bound CD4-binding site (CD4bs) ligands with 3-12 MUm affinity and elicited a
      modest neutralizing antibody response in rabbits. In this study, we have
      optimized ODEC using consensus sequence design, cyclic permutation, and structure
      guided mutations to generate a number of variants with improved yields,
      biophysical properties, stabilities, and affinities (KD of 10-50 nm) for various
      CD4bs targeting broadly neutralizing antibodies, including the germline-reverted
      version of the broadly neutralizing antibody VRC01. In contrast to ODEC, the
      optimized immunogens elicited high anti-gp120 titers in rabbits as early as 6
      weeks post-immunization, before any gp120 boost was given. Following two gp120
      boosts, sera collected at week 22 showed cross-clade neutralization of tier 1 HIV
      1 viruses. Using a number of different prime/boost combinations, we have
      identified a cyclically permuted OD fragment as the best priming immunogen, and a
      trimeric, cyclically permuted gp120 as the most suitable boosting molecule among
      the tested immunogens. This study also provides insights into some of the
      biophysical correlates of improved immunogenicity.

PMID- 30093410
TI  - Distinct substrate specificities of human GlcNAc-6-sulfotransferases revealed by
      mass spectrometry-based sulfoglycomic analysis.
AB  - Sulfated glycans are known to be involved in several glycan-mediated cell
      adhesion and recognition pathways. Our mRNA transcript analyses on the genes
      involved in synthesizing GlcNAc-6-O-sulfated glycans in human colon cancer
      tissues indicated that GlcNAc6ST-2 (CHST4) is preferentially expressed in cancer
      cells compared with nonmalignant epithelial cells among the three known major
      GlcNAc-6-O-sulfotransferases. On the contrary, GlcNAc6ST-3 (CHST5) was only
      expressed in nonmalignant epithelial cells, whereas GlcNAc6ST-1 (CHST2) was
      expressed equally in both cancerous and nonmalignant epithelial cells. These
      results suggest that 6-O-sulfated glycans that are synthesized only by GlcNAc6ST
      2 may be highly colon cancer-specific, as supported by immunohistochemical
      staining of cancer cells using the MECA-79 antibody known to be relatively
      specific to the enzymatic reaction products of GlcNAc6ST-2. By more precise MS
      based sulfoglycomic analyses, we sought to further infer the substrate
      specificities of GlcNAc6STs via a definitive mapping of various sulfo-glycotopes
      and O-glycan structures expressed in response to overexpression of transfected
      GlcNAc6STs in the SW480 colon cancer cell line. By detailed MS/MS sequencing,
      GlcNAc6ST-3 was shown to preferentially add sulfate onto core 2-based O-glycan
      structures, but it does not act on extended core 1 structures, whereas GlcNAc6ST
      1 prefers core 2-based O-glycans to extended core 1 structures. In contrast,
      GlcNAc6ST-2 could efficiently add sulfate onto both extended core 1- and core 2
      based O-glycans, leading to the production of unique sulfated extended core 1
      structures such as R-GlcNAc(6-SO3 -)beta1-3Galbeta1-4GlcNAc(6-SO3 -)beta1
      3Galbeta1-3GalNAcalpha, which are good candidates to be targeted as cancer
      specific glycans.

PMID- 30093414
TI  - Tobacco company strategies to identify and promote the benefits of nicotine.
AB  - BACKGROUND: In response to a changing regulatory and consumer landscape, tobacco
      companies developed new strategies to promote cigarettes and smoking. We examined
      one of these strategies: to fund and conduct scientific research related to
      potential benefits of nicotine, and to use their findings to promote nicotine.
      METHODS: Qualitative analysis of previously secret tobacco industry documents
      from the Truth (formerly Legacy) Tobacco Documents Library
      (industrydocuments.library.ucsf.edu/tobacco), triangulated with data from other
      sources, including the online search engine Google, from the 1970s to December
      2017. RESULTS: After publication of the 1988 Surgeon General's report on nicotine
      addiction, tobacco companies (particularly RJ Reynolds) intensified efforts to
      promote the benefits of nicotine while downplaying its addictiveness and health
      risks. Activities included building relationships with academic institutions and
      funding scientific studies of the benefits of nicotine on cognition and other
      performance areas through intramural and extramural programmes. Companies then
      promoted their research findings through public relations campaigns, often
      minimising nicotine's health risks by comparing it to caffeine or coffee. These
      comparisons appeared in highly publicised scientific meetings and interviews with
      the press. Nicotine-positive messages reappeared in the popular press and on some
      company websites in the 2010s. CONCLUSIONS: Tobacco companies implemented
      strategies to promote benefits of nicotine to scientific and general audiences
      while minimising its health risks. These strategies reappeared at the time novel
      tobacco products like electronic cigarettes were introduced. A greater awareness
      of the source of claims related to purported benefits of nicotine could inform
      discussions about emerging tobacco products.

PMID- 30093411
TI  - Ectopic fibroblast growth factor receptor 1 promotes inflammation by promoting
      nuclear factor-kappaB signaling in prostate cancer cells.
AB  - Initiation of expression of fibroblast growth factor receptor 1 (FGFR1)
      concurrent with loss of FGFR2 expression is a well-documented event in the
      progression of prostate cancer (PCa). Although it is known that some FGFR
      isoforms confer advantages in cell proliferation and survival, the mechanism by
      which the subversion of different FGFR isoforms contributes to PCa progression is
      incompletely understood. Here, we report that fibroblast growth factor (FGF)
      promotes NF-kappaB signaling in PCa cells and that this increase is associated
      with FGFR1 expression. Disruption of FGFR1 kinase activity abrogated both FGF
      activity and NF-kappaB signaling in PCa cells. Of note, the three common
      signaling pathways downstream of FGFR1 kinase, extracellular signal-regulated
      kinase 1/2 (ERK1/2), phosphoinositide 3-kinase (PI3K/AKT), and phosphoinositide
      phospholipase Cgamma (PLCgamma), were not required for FGF-mediated NF-kappaB
      signaling. Instead, transforming growth factor beta-activating kinase 1 (TAK1), a
      central regulator of the NF-kappaB pathway, was required for FGFR1 to stimulate
      NF-kappaB signaling. Moreover, we found that FGFR1 promotes NF-kappaB signaling
      in PCa cells by reducing TAK1 degradation and thereby supporting sustained NF
      kappaB activation. Consistently, Fgfr1 ablation in the transgenic adenocarcinoma
      of the mouse prostate (TRAMP) model reduced inflammation in the tumor
      microenvironment. In contrast, activation of the FGFR1 kinase in the
      juxtaposition of chemical-induced dimerization (CID) and kinase 1 (JOCK1) mouse
      model increased inflammation. As inflammation plays an important role in PCa
      initiation and progression, these findings suggest that ectopically expressed
      FGFR1 promotes PCa progression, at least in part, by increasing inflammation in
      the tumor microenvironment.

PMID- 30093413
TI  - Reactive oxygen species in plant development.
AB  - Reactive oxygen species (ROS) are produced by metabolic pathways in almost all
      cells. As signaling components, ROS are best known for their roles in abiotic and
      biotic stress-related events. However, recent studies have revealed that they are
      also involved in numerous processes throughout the plant life cycle, from seed
      development and germination, through to root, shoot and flower development. Here,
      we provide an overview of ROS production and signaling in the context of plant
      growth and development, highlighting the key functions of ROS and their
      interactions with plant phytohormonal networks.

PMID- 30093415
TI  - Distributional health and financial benefits of increased tobacco taxes in
      Colombia: results from a modelling study.
AB  - BACKGROUND: In Colombia, smoking is the second leading modifiable risk factor for
      premature mortality. In December 2016, Colombia passed a major tax increase on
      tobacco products in an effort to decrease smoking and improve population health.
      While tobacco taxes are known to be highly effective in reducing the prevalence
      of smoking, they are often criticised as being regressive in consumption. This
      analysis attempts to assess the distributional impact (across socioeconomic
      groups) of the new tax on selected health and financial outcomes. METHODS: This
      study builds on extended cost-effectiveness analysis methods to study the new
      tobacco tax in Colombia, and estimates, over a time period of 20 years and across
      income quintiles of the current urban population (80% of the country population),
      the years of life gained with smoking cessation and the increased tax revenues,
      all associated with a 70% relative price increase of the pack of cigarettes.
      Where possible, we use parameters that vary by income quintile, including price
      elasticity of demand for cigarettes (average of -0.44 estimated from household
      survey data). FINDINGS: Over 20 years, the tax increase would lead to an
      estimated 191 000 years of life gained among Colombia's current urban population,
      with the largest gains among the bottom two income quintiles. The additional
      annual tax revenues raised would amount to about 2%-4% of Colombia's annual
      government health expenditure, with the poorest quintiles bearing the smallest
      tax burden increase. CONCLUSIONS: The tobacco tax increase passed by Colombia has
      substantial implications for the country's population health and financial well
      being, with large benefits likely to accrue to the two poorest quintiles of the
      population.

PMID- 30093412
TI  - Spatiotemporal Gene Expression Analysis of the Caenorhabditis elegans Germline
      Uncovers a Syncytial Expression Switch.
AB  - Developmental programs are executed by tightly controlled gene regulatory
      pathways. Here, we combined the unique sample retrieval capacity afforded by
      laser capture microscopy with analysis of mRNA abundance by CEL-Seq (cell
      expression by linear amplification and sequencing) to generate a spatiotemporal
      gene expression map of the Caenorhabditis elegans syncytial germline from adult
      hermaphrodites and males. We found that over 6000 genes exhibit spatiotemporally
      dynamic expression patterns throughout the hermaphrodite germline, with two
      dominant groups of genes exhibiting reciprocal shifts in expression at late
      pachytene during meiotic prophase I. We found a strong correlation between
      restricted spatiotemporal expression and known developmental and cellular
      processes, indicating that these gene expression changes may be an important
      driver of germ cell progression. Analysis of the male gonad revealed a shift in
      gene expression at early pachytene and upregulation of subsets of genes following
      the meiotic divisions, specifically in early and late spermatids, mostly
      transcribed from the X chromosome. We observed that while the X chromosome is
      silenced throughout the first half of the gonad, some genes escape this control
      and are highly expressed throughout the germline. Although we found a strong
      correlation between the expression of genes corresponding to CSR-1-interacting
      22G-RNAs during germ cell progression, we also found that a large fraction of
      genes may bypass the need for CSR-1-mediated germline licensing. Taken together,
      these findings suggest the existence of mechanisms that enable a shift in gene
      expression during prophase I to promote germ cell progression.

PMID- 30093416
TI  - The Importance of Incorporating OCT2 Plasma Membrane Expression and Membrane
      Potential in IVIVE of Metformin Renal Secretory Clearance.
AB  - Transporter expression, determined by quantitative proteomics, together with PBPK
      models is a promising approach for in vitro-to-in vivo extrapolation (IVIVE) of
      transporter-mediated drug clearance. OCT2-expressing HEK293 and MDCKII cells were
      used to predict in vivo renal secretory clearance (CLr,sec) of metformin. [14C]
      Metformin uptake clearance in OCT2-expressing cells was determined and scaled to
      in vivo CLr,sec by using OCT2 expression in the cells versus the human kidney
      cortex. Through quantitative targeted proteomics, the total expression of OCT2 in
      HEK293, MDCKII cells, and human kidney cortex was 369.4 +/- 26.8, 19 +/- 1.1, and
      7.6 +/- 3.8 pmol/mg cellular protein, respectively. The expression of OCT2 in the
      plasma membrane of HEK293 and MDCKII cells, measured using an optimized
      biotinylation method followed by quantitative proteomics, was 30.2% and 51.6%,
      respectively. After correcting for percent of OCT2 expressed in the plasma
      membrane and the resting membrane potential (millivolts) difference between the
      OCT2-expressing cells and the renal epithelial cells, the predicted CLr,sec of
      metformin was 250.7 ml/min, a value within the range of the observed CLr,sec of
      metformin. These data demonstrate the promise of using quantitative proteomics
      for IVIVE of transporter-mediated drug clearance and highlight the importance of
      quantifying plasma membrane expression of transporters and utilizing cells that
      mimic the in vivo mechanism(s) of transport of drugs.

PMID- 30093417
TI  - Humanized UGT1 Mice, Regulation of UGT1A1, and the Role of the Intestinal Tract
      in Neonatal Hyperbilirubinemia and Breast Milk-Induced Jaundice.
AB  - Neonatal hyperbilirubinemia and the onset of bilirubin encephalopathy and
      kernicterus result in part from delayed expression of UDP-glucuronosyltransferase
      1A1 (UGT1A1) and the ability to metabolize bilirubin. It is generally believed
      that acute neonatal forms of hyperbilirubinemia develop due to an inability of
      hepatic UGT1A1 to metabolize efficiently bilirubin for clearance through the
      hepatobiliary tract. Newly developed mouse models designed to study bilirubin
      metabolism have led to new insight into the role of the intestinal tract in
      controlling neonatal hyperbilirubinemia. Humanization of mice with the UGT1 locus
      (hUGT1 mice) and the UGT1A1 gene provide a unique tool to study the onset of
      hyperbilirubinemia since the human UGT1A1 gene is developmentally regulated
      during the neonatal period in hUGT1 mice. A new mechanism outlying developmental
      expression of intestinal UGT1A1 is presented and its implications in the control
      of neonatal hyperbilirubinemia discussed. New findings linking breast milk
      protection against necrotizing enterocolitis and intestinal control of UGT1A1 may
      help explain the contribution of breast milk toward the development of neonatal
      hyperbilirubinemia. Our findings outline a new model that includes an active
      intestinal ROS /IkappaB kinase/nuclear receptor corepressor 1 loop that can be
      applied to an understanding of breast milk-induced jaundice.

PMID- 30093419
TI  - Development of a Gill Assay Library for Ecological Proteomics of Threespine
      Sticklebacks (Gasterosteus aculeatus).
AB  - A data-independent acquisition (DIA) assay library for quantitative analyses of
      proteome dynamics has been developed for gills of threespine sticklebacks
      (Gasterosteus aculeatus). A raw spectral library was generated by data-dependent
      acquisition (DDA) and annotation of tryptic peptides to MSMS spectra and protein
      database identifiers. The assay library was constructed from the raw spectral
      library by removal of low-quality, ambiguous, and low-signal peptides. Only
      unique proteins represented by at least two peptides are included in the assay
      library, which consists of 1506 proteins, 5074 peptides, 5104 precursors, and
      25,322 transitions. This assay library was used with DIA data to identify
      biochemical differences in gill proteomes of four populations representing
      different eco- and morpho-types of threespine sticklebacks. The assay library
      revealed unique and reproducible proteome signatures. Warm-adapted, low-plated,
      brackish-water fish from Laguna de la Bocana del Rosario (Mexico) show elevated
      HSP47, extracellular matrix, and innate immunity proteins whereas several
      immunoglobulins, interferon-induced proteins, ubiquitins, proteolytic enzymes,
      and nucleic acid remodeling proteins are reduced. Fully-plated, brackish-water
      fish from Westchester Lagoon (Alaska) display elevated ion regulation, GTPase
      signaling, and contractile cytoskeleton proteins, altered abundances of many
      ribosomal, calcium signaling and immunity proteins, and depleted transcriptional
      regulators and metabolic enzymes. Low-plated freshwater fish from Lake Solano
      (California) have elevated inflammasomes and proteolytic proteins whereas several
      iron containing and ion regulatory proteins are reduced. Gills of fully-plated,
      marine fish from Bodega Harbor (California) have elevated oxidative metabolism
      enzymes and reduced transglutaminase 2, collagens, and clathrin heavy chains.
      These distinct proteome signatures represent targets for testing ecological and
      evolutionary influences on molecular mechanisms of gill function in threespine
      sticklebacks. Furthermore, the gill assay library represents a model for other
      tissues and paves the way for accurate and reproducible network analyses of
      environmental context-dependent proteome dynamics in complex organisms.

PMID- 30093421
TI  - Action on responsible antimicrobial use.

PMID- 30093420
TI  - gpGrouper: A Peptide Grouping Algorithm for Gene-Centric Inference and
      Quantitation of Bottom-Up Proteomics Data.
AB  - In quantitative mass spectrometry, the method by which peptides are grouped into
      proteins can have dramatic effects on downstream analyses. Here we describe
      gpGrouper, an inference and quantitation algorithm that offers an alternative
      method for assignment of protein groups by gene locus and improves pseudo
      absolute iBAQ quantitation by weighted distribution of shared peptide areas. We
      experimentally show that distributing shared peptide quantities based on unique
      peptide peak ratios improves quantitation accuracy compared with conventional
      winner-take-all scenarios. Furthermore, gpGrouper seamlessly handles two-species
      samples such as patient-derived xenografts (PDXs) without ignoring the host
      species or species-shared peptides. This is a critical capability for proper
      evaluation of proteomics data from PDX samples, where stromal infiltration varies
      across individual tumors. Finally, gpGrouper calculates peptide peak area (MS1)
      based expression estimates from multiplexed isobaric data, producing iBAQ results
      that are directly comparable across label-free, isotopic, and isobaric proteomics
      approaches.

PMID- 30093422
TI  - Livestock industry set to hit 2020 antibiotics targets.

PMID- 30093424
TI  - Are farm assurance scheme inspections sufficient?

PMID- 30093426
TI  - Maximum sentencing for animal abuse set to rise.

PMID- 30093428
TI  - Protecting the UK from a disease outbreak.
AB  - For the first time, the UK government has published a biosecurity strategy.
      Georgina Mills reports.

PMID- 30093429
TI  - Self-styled geek CEO says it's 'all about data'.
AB  - Andrei Balta, chief executive of Pets at Home Vet Group, talks to Josh Loeb about
      how to crack the retail and vet practice business.

PMID- 30093418
TI  - P450-Humanized and Human Liver Chimeric Mouse Models for Studying Xenobiotic
      Metabolism and Toxicity.
AB  - Preclinical evaluation of drug candidates in experimental animal models is an
      essential step in drug development. Humanized mouse models have emerged as a
      promising alternative to traditional animal models. The purpose of this mini
      review is to provide a brief survey of currently available mouse models for
      studying human xenobiotic metabolism. Here, we describe both genetic humanization
      and human liver chimeric mouse models, focusing on the advantages and limitations
      while outlining their key features and applications. Although this field of
      biomedical science is relatively young, these humanized mouse models have the
      potential to transform preclinical drug testing and eventually lead to a more
      cost-effective and rapid development of new therapies.

PMID- 30093432
TI  - Small animal disease surveillance: pruritus and Pseudomonas skin infections.

PMID- 30093433
TI  - Perioperative hypothermia: a preventable complication.

PMID- 30093435
TI  - Using BVA policy to improve farm animal health and welfare.

PMID- 30093436
TI  - What underpins BVA's ethical decisions?

PMID- 30093437
TI  - German Shepherd Dog League.

PMID- 30093438
TI  - Establishing a UK surveillance forum.

PMID- 30093439
TI  - Bog asphodel toxicity.

PMID- 30093440
TI  - What underpins BVA's ethical decisions?

PMID- 30093441
TI  - Gamebird antibiotic use reduction.

PMID- 30093442
TI  - We need to make more use of technology in the slaughter industry to improve
      welfare.
AB  - Rebeca Garcia Pinillos explains how the use of advanced technologies could help
      drive forward improvements in farm animal welfare during slaughter processes, as
      well as staff wellbeing.

PMID- 30093443
TI  - Vegans aren't 'brainwashing' people.

PMID- 30093446
TI  - Rates of ERBB2 Alterations across Melanoma Subtypes and a Complete Response to
      Trastuzumab Emtansine in an ERBB2-Amplified Acral Melanoma.
AB  - PURPOSE: Patients with BRAF V600 wild-type melanoma whose tumors progress on
      checkpoint inhibition currently have limited therapeutic options, and additional
      rational treatment targets are needed. ERBB2 alterations may be amenable to
      targeted inhibition, but the rate of ERBB2 alterations across melanoma subtypes
      is not well described. PATIENTS AND METHODS: All patients with nonuveal melanoma
      (cutaneous, acral, mucosal, and unknown primary) whose tumors underwent multigene
      sequencing with MSK-IMPACT at Memorial Sloan Kettering Cancer Center (New York,
      NY) from 2014 to 2018 were reviewed for known or likely oncogenic somatic
      alterations in ERBB2 and the other known canonical driver genes BRAF, NRAS, KIT,
      NF1, GNAQ, and GNA11. RESULTS: A patient with acral melanoma resistant to
      checkpoint inhibition was found to have ERBB2 amplification and achieved a
      durable complete response to trastuzumab emtansine. Tumor sequencing results from
      732 melanoma cases were analyzed for ERBB2 and canonical driver gene alterations.
      ERBB2 amplifications were detected in acral (3%) and mucosal (3%) melanomas.
      ERBB2 mutations were found in cutaneous (1%), acral (2%), and mucosal (2%)
      subtypes and frequently cooccurred with NF1 alterations. Among the 140 patients
      whose tumors lacked canonical driver alterations, ERBB2 amplifications were
      detected in acral (7%) and mucosal (6%) melanomas. CONCLUSIONS: ERBB2
      amplification is present in a minority of acral lentiginous and mucosal
      melanomas. Activating mutations in ERBB2 were identified in nonuveal melanoma
      subtypes and are frequently comutated with canonical drivers. HER2 could
      represent a therapeutically relevant target across melanoma subtypes.

PMID- 30093447
TI  - Ultrahigh Dose-rate Radiotherapy: Next Steps for FLASH-RT.
AB  - A new way of delivering radiotherapy at very high dose rates is described and
      compared with conventional radiotherapy. The ultrahigh dose-rate therapy reduces
      damage to normal pig skin and exerts potent activity against spontaneous nasal
      tumors in cat patients. The implications for clinical development of this
      approach are discussed. Clin Cancer Res; 1-3. (c)2018 AACR. See related article
      by Vozenin et al.

PMID- 30093448
TI  - Role of the RANK/RANKL Pathway in Multiple Myeloma.
AB  - Receptor activator of nuclear factor-kappa B (RANK) and its ligand, RANKL, are
      expressed in a variety of tissues throughout the body; their primary role is in
      the regulation of bone remodeling and development of the immune system.
      Consistent with these functions, evidence exists for a role of RANK/RANKL in all
      stages of tumorigenesis, from cell proliferation and carcinogenesis to epithelial
      mesenchymal transition to neoangiogenesis and intravasation to metastasis to bone
      resorption and tumor growth in bone. Results from current studies also point to a
      role of RANK/RANKL signaling in patients with multiple myeloma, who have
      increased serum levels of soluble RANKL and an imbalance in RANKL and
      osteoprotegerin. Current therapies for patients with multiple myeloma demonstrate
      that RANKL may be released by tumor cells or osteoprogenitor cells. This article
      will review currently available evidence supporting a role for RANK/RANKL
      signaling in tumorigenesis, with a focus on patients with multiple myeloma. Clin
      Cancer Res; 1-9. (c)2018 AACR.

PMID- 30093449
TI  - Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for
      Patients with Relapsed or Refractory Neuroblastoma.
AB  - Purpose: In phase I testing, alisertib tablets with irinotecan and temozolomide
      showed significant antitumor activity in patients with neuroblastoma. This study
      sought to confirm activity of this regimen; evaluate an alisertib oral solution;
      and evaluate biomarkers of clinical outcomes.Experimental Design: We conducted a
      two-stage phase II trial of alisertib tablets (60 mg/m2/dose * 7 days),
      irinotecan (50 mg/m2/dose i.v. * 5 days), and temozolomide (100 mg/m2/dose orally
      * 5 days) in patients with relapsed or refractory neuroblastoma. The primary
      endpoint was best objective response. A separate cohort was treated with
      alisertib at 45 mg/m2 using oral solution instead of tablets. Exploratory
      analyses sought to identify predictors of toxicity, response, and progression
      free survival (PFS) using pooled data from phase I, phase II, and oral solution
      cohorts.Results: Twenty and 12 eligible patients were treated in the phase II and
      oral solution cohorts, respectively. Hematologic toxicities were the most common
      adverse events. In phase II, partial responses were observed in 19 evaluable
      patients (21%). The estimated PFS at 1 year was 34%. In the oral solution cohort,
      3 patients (25%) had first cycle dose-limiting toxicity (DLT). Alisertib oral
      solution at 45 mg/m2 had significantly higher median C max and exposure compared
      with tablets at 60 mg/m2 Higher alisertib trough concentration was associated
      with first cycle DLT, whereas MYCN amplification was associated with inferior
      PFS.Conclusions: This combination shows antitumor activity, particularly in
      patients with MYCN nonamplified tumors. Data on an alisertib oral solution expand
      the population able to be treated with this agent. Clin Cancer Res; 24(24); 1-8.
      (c)2018 AACR.

PMID- 30093450
TI  - Single-Cell Analyses of Prostate Cancer Liquid Biopsies Acquired by Apheresis.
AB  - Purpose: Circulating tumor cells (CTCs) have clinical relevance, but their study
      has been limited by their low frequency.Experimental Design: We evaluated liquid
      biopsies by apheresis to increase CTC yield from patients suffering from
      metastatic prostate cancer, allow precise gene copy-number calls, and study
      disease heterogeneity.Results: Apheresis was well tolerated and allowed the
      separation of large numbers of CTCs; the average CTC yield from 7.5 mL of
      peripheral blood was 167 CTCs, whereas the average CTC yield per apheresis (mean
      volume: 59.5 mL) was 12,546 CTCs. Purified single CTCs could be isolated from
      apheresis product by FACS sorting; copy-number aberration (CNA) profiles of 185
      single CTCs from 14 patients revealed the genomic landscape of lethal prostate
      cancer and identified complex intrapatient, intercell, genomic heterogeneity
      missed on bulk biopsy analyses.Conclusions: Apheresis facilitated the capture of
      large numbers of CTCs noninvasively with minimal morbidity and allowed the
      deconvolution of intrapatient heterogeneity and clonal evolution. Clin Cancer
      Res; 24(22); 5635-44. (c)2018 AACR.

PMID- 30093451
TI  - Identification of Tissue-Specific DNA Methylation Signatures for Thyroid Nodule
      Diagnostics.
AB  - Purpose: Thyroid cancer is frequently difficult to diagnose due to an overlap of
      cytologic features between malignant and benign nodules. This overlap leads to
      unnecessary removal of the thyroid in patients without cancer. While providing
      some improvement over cytopathologic diagnostics, molecular methods frequently
      fail to provide a correct diagnosis for thyroid nodules. These approaches are
      based on the difference between cancer and adjacent thyroid tissue and assume
      that adjacent tissues are the same as benign nodules. However, in contrast to
      adjacent tissues, benign thyroid nodules can contain genetic alterations that can
      be found in cancer.Experimental Design: For the development of a new molecular
      diagnostic test for thyroid cancer, we evaluated DNA methylation in 109 thyroid
      tissues by using genome-wide single-base resolution DNA methylation analysis. The
      test was validated in a retrospective cohort containing 65 thyroid
      nodules.Results: By conducting reduced representation bisulfite sequencing in 109
      thyroid specimens, we found significant differences between adjacent tissue,
      benign nodules, and cancer. These tissue-specific signatures are strongly linked
      to active enhancers and cancer-associated genes. Based on these signatures, we
      developed a new epigenetic approach for thyroid diagnostics. According to the
      validation cohort, our test has an estimated specificity of 97% [95% confidence
      interval (CI), 81-100], sensitivity of 100% (95% CI, 87-100), positive predictive
      value of 97% (95% CI, 83-100), and negative predictive value of 100% (95% CI, 86
      100).Conclusions: These data show that epigenetic testing can provide outstanding
      diagnostic accuracy for thyroid nodules.

PMID- 30093452
TI  - Targeting the CDK4/6-Rb Pathway Enhances Response to PI3K Inhibition in PIK3CA
      Mutant Lung Squamous Cell Carcinoma.
AB  - PURPOSE: Lung squamous cell carcinoma (LUSC) is a major subtype of non-small cell
      lung cancer characterized by multiple genetic alterations, particularly PI3K
      pathway alterations which have been identified in over 50% of LUSC cases. Despite
      being an attractive target, single-agent PI3K inhibitors have demonstrated modest
      response in LUSC. Thus, novel combination therapies targeting LUSC are needed.
      EXPERIMENTAL DESIGN: PI3K inhibitors alone and in combination with CDK4/6
      inhibitors were evaluated in previously established LUSC patient-derived
      xenografts (PDX) using an in vivo screening method. Screening results were
      validated with in vivo expansion to 5 to 8 mice per arm. Pharmacodynamics studies
      were performed to confirm targeted inhibition of compounds. RESULTS: Consistent
      with results from The Cancer Genome Atlas analysis of LUSC, genomic profiling of
      our large cohort of LUSC PDX models identified PI3K pathway alterations in over
      50% of the models. In vivo screening using PI3K inhibitors in 12 of these models
      identified PIK3CA mutation as a predictive biomarker of response (<20% tumor
      growth compared with baseline/vehicle). Combined inhibition of PI3K and CDK4/6 in
      models with PIK3CA mutation resulted in greater antitumor effects compared with
      either monotherapy alone. In addition, the combination of the two drugs achieved
      targeted inhibition of the PI3K and cell-cycle pathways. CONCLUSIONS: PIK3CA
      mutations predict response to PI3K inhibitors in LUSC. Combined PI3K and CDK4/6
      inhibition enhances response to either single agents alone. Our findings provide
      a rationale for clinical testing of combined PI3K and CDK4/6 inhibitors in PIK3CA
      mutant LUSC.

PMID- 30093454
TI  - Early Reduction in ctDNA Predicts Survival in Patients with Lung and Bladder
      Cancer Treated with Durvalumab.
AB  - Purpose: Immunotherapy has transformed the treatment of many solid tumors, with
      some patients deriving long-term benefit, but how to identify such patients
      remains unclear. Somatic mutations detected in circulating tumor DNA (ctDNA) from
      plasma can be an indicator of disease progression, response to therapy, and
      clonality of primary and metastatic lesions. Hence, ctDNA analysis can provide a
      valuable noninvasive and tumor-specific marker for longitudinal monitoring of
      tumor burden. We explored the use of ctDNA to predict survival on durvalumab, an
      anti-PD-L1 therapy.Experimental Design: Variant allele frequencies (VAF) of
      somatic mutations in 73 genes were assessed in ctDNA using targeted sequencing in
      a discovery cohort consisting of 28 patients with non-small cell lung cancer
      (NSCLC) and two validation NSCLC and urothelial cancer (UC) cohorts of 72 and 29
      patients, respectively, to correlate ctDNA changes with clinical
      outcomes.Results: Somatic variants were detected in 96% of patients. Changes in
      VAF preceded radiographic responses, and patients with reduction in VAF at 6
      weeks had significantly greater reduction in tumor volume, with longer
      progression-free and overall survival.Conclusions: ctDNA VAF changes are strongly
      correlated with duration of treatment, antitumor activity, and clinical outcomes
      in NSCLC and UC. Early on-treatment reduction in ctDNA VAF may be a useful
      predictor of long-term benefit from immunotherapy. Prospective studies should
      validate these findings and the value of utilizing early changes in ctDNA for
      therapeutic decision making by identifying nonresponders to checkpoint inhibitor
      monotherapies and guiding combination therapies. Clin Cancer Res; 1-11. (c)2018
      AACR.

PMID- 30093453
TI  - Intratumoral G100, a TLR4 Agonist, Induces Antitumor Immune Responses and Tumor
      Regression in Patients with Merkel Cell Carcinoma.
AB  - Purpose: G100 is a toll-like receptor 4 (TLR4) agonist that triggers innate and
      adaptive antitumor immune responses in preclinical models. This pilot study
      assessed the safety, efficacy, and immunologic activity of intratumoral (IT)
      administration of G100 in patients with Merkel cell carcinoma (MCC).Experimental
      Design: Patients with locoregional MCC (n = 3; cohort A) received neoadjuvant IT
      G100 (2 weekly doses at 5 MUg/dose) followed by surgery and radiotherapy;
      patients with metastatic MCC (n = 7; cohort B) received 3 doses in a 6-week cycle
      and could receive additional cycles with/without radiotherapy.Results: IT G100
      was safe and feasible in both neoadjuvant and metastatic settings. Treatment
      related adverse events were mostly grade 1 or 2 injection-site reactions. IT G100
      led to increased inflammation in the injected tumors with infiltration of CD8+
      and CD4+ T cells and activation of immune-related genes. These proinflammatory
      changes were associated with local tumor regression and appeared to promote
      systemic immunity. All 3 cohort A patients successfully completed therapy; 2
      patients remain recurrence free at 44+ and 41+ months, including 1 with a
      pathologic complete response after G100 alone. In cohort B, 2 patients achieved
      sustained partial responses, both lasting 33+ months after 2 cycles of
      therapy.Conclusions: In this first-in-human study, IT G100 induced antitumor
      immune responses, demonstrated acceptable safety, and showed encouraging clinical
      activity. Clin Cancer Res; 1-11. (c)2018 AACR.

PMID- 30093455
TI  - Race, Ethnicity, and End-of-Life Care in Dialysis Patients in the United States.
AB  - BACKGROUND: End-of-life care is a prominent consideration in patients on
      maintenance dialysis, especially when death appears imminent and quality of life
      is poor. To date, examination of race- and ethnicity-associated disparities in
      end-of-life care for patients with ESRD has largely been restricted to
      comparisons of white and black patients. METHODS: We performed a retrospective
      national study using United States Renal Data System files to determine whether
      end-of-life care in United States patients on dialysis is subject to racial or
      ethnic disparity. The primary outcome was a composite of discontinuation of
      dialysis and death in a nonhospital or hospice setting. RESULTS: Among 1,098,384
      patients on dialysis dying between 2000 and 2014, the primary outcome was less
      likely in patients from any minority group compared with the non-Hispanic white
      population (10.9% versus 22.6%, P<0.001, respectively). We also observed similar
      significant disparities between any minority group and non-Hispanic whites for
      dialysis discontinuation (16.7% versus 31.2%), as well as hospice (10.3% versus
      18.1%) and nonhospital death (34.4% versus 46.4%). After extensive covariate
      adjustment, the primary outcome was less likely in the combined minority group
      than in the non-Hispanic white population (adjusted odds ratio, 0.55; 95%
      confidence interval, 0.55 to 0.56; P<0.001). Individual minority groups (non
      Hispanic Asian, non-Hispanic black, non-Hispanic Native American, and Hispanic)
      were significantly less likely than non-Hispanic whites to experience the primary
      outcome. This disparity was especially pronounced for non-Hispanic Native
      American and Hispanic subgroups. CONCLUSIONS: There appear to be substantial race
      and ethnicity-based disparities in end-of-life care practices for United States
      patients receiving dialysis.

PMID- 30093457
TI  - Fibroblast Growth Factor-23 May Follow Cardiovascular Disease Rather than Causing
      It in Chronic Kidney Disease.

PMID- 30093458
TI  - Phosphate Binder, Ferric Citrate, Attenuates Anemia, Renal Dysfunction, Oxidative
      Stress, Inflammation, and Fibrosis in 5/6 Nephrectomized CKD Rats.
AB  - Chronic kidney disease (CKD) causes anemia and impairs intestinal iron
      absorption. However, use of the phosphate binder ferric citrate (FC) increases
      body iron stores and hemoglobin levels in CKD patients. By intensifying oxidative
      stress and inflammation iron overload resulting from excessive use of intravenous
      iron can accelerate CKD progression. The present study explored the route of
      absorption and tissue distribution of iron with FC administration and its effect
      on renal function, histology, and inflammatory, oxidative, and fibrosis pathways
      in CKD rats. Male Sprague Dawley rats were randomized to sham-operated control
      (CTL) group and 5/6 nephrectomized (CKD) groups fed either regular or 4% FC
      supplemented diets for 6 weeks. Animals were then sacrificed, and blood and
      target tissues were harvested and processed. The untreated CKD rats exhibited
      anemia, hypertension, upregulation of renal tissue inflammatory, oxidative, and
      fibrotic pathways, impaired nuclear translocation, and downregulation of Nrf2's
      target gene products and depletion of colonic epithelial tight junction proteins.
      FC administration raised serum iron, improved anemia, attenuated
      hyperphosphatemia, partially improved renal function, reduced oxidative stress,
      inflammation, and fibrosis, and restored colonic epithelial zonula occludens-1
      protein abundance. Tissue iron staining detected presence of iron in epithelial
      cells and subepithelium of colon and in renal proximal tubules. In conclusion
      ferric citrate administration resulted in modest amelioration of renal function
      and histology and partial improvements of fibrosis, inflammation, and oxidative
      stress in the kidney tissues of CKD rats.

PMID- 30093459
TI  - PBI-4050 Reduces Stellate Cell Activation and Liver Fibrosis through Modulation
      of Intracellular ATP Levels and the Liver Kinase B1/AMP-Activated Protein
      Kinase/Mammalian Target of Rapamycin Pathway.
AB  - Hepatic fibrosis is a major cause of morbidity and mortality for which there is
      currently no effective therapy. We previously showed that 2-(3
      pentylphenyl)acetic acid (PBI-4050) is a dual G protein-coupled receptor GPR40
      agonist/GPR84 antagonist that exerts antifibrotic, anti-inflammatory, and
      antiproliferative action. We evaluated PBI-4050 for the treatment of liver
      fibrosis in vivo and elucidated its mechanism of action on human hepatic stellate
      cells (HSCs). The antifibrotic effect of PBI-4050 was evaluated in carbon
      tetrachloride (CCl4)- and bile duct ligation-induced liver fibrosis rodent
      models. Treatment with PBI-4050 suppressed CCl4-induced serum aspartate
      aminotransferase levels, inflammatory marker nitric oxide synthase, epithelial to
      mesenchymal transition transcription factor Snail, and multiple profibrotic
      factors. PBI-4050 also decreased GPR84 mRNA expression in CCl4-induced injury,
      while restoring peroxisome proliferator-activated receptor gamma (PPARgamma) to
      the control level. Collagen deposition and alpha-smooth muscle actin (alpha-SMA)
      protein levels were also attenuated by PBI-4050 treatment in the bile duct
      ligation rat model. Transforming growth factor-beta-activated primary HSCs were
      used to examine the effect of PBI-4050 and its mechanism of action in vitro. PBI
      4050 inhibited HSC proliferation by arresting cells in the G0/G1 cycle phase.
      Subsequent analysis demonstrated that PBI-4050 signals through a reduction of
      intracellular ATP levels, activation of liver kinase B1 (LKB1) and AMP-activated
      protein kinase (AMPK), and blockade of mammalian target of rapamycin (mTOR),
      resulting in reduced protein and mRNA levels of alpha-SMA and connective tissue
      growth factor and restored PPARgamma mRNA expression. Our findings suggest that
      PBI-4050 may exert antifibrotic activity in the liver through a novel mechanism
      of action involving modulation of intracellular ATP levels and the LKB1/AMPK/mTOR
      pathway in stellate cells, and PBI-4050 may be a promising agent for treating
      liver fibrosis.

PMID- 30093460
TI  - Peek through the smoke: a report of moyamoya disease in a 32-year-old female
      patient presenting with ischaemic stroke.
AB  - Moyamoya disease is a vasculopathy causing chronic progressive stenosis and
      occlusion of the large arteries of the circle of Willis that could lead to brain
      ischaemia. The condition may also present with haemorrhagic strokes. This is a
      case report of moyamoya disease in a 32-year-old woman presenting with ischaemic
      stroke. The report describes her inpatient stay and investigations and
      findings.The report reviews the main aspects of moyamoya disease definition,
      epidemiology, clinical features, diagnosis, classification and treatment. This
      case is interesting because her first presentation occurred after 3 months of her
      second delivery. Whether the different physiological stresses of pregnancy, child
      birth and puerperium have had some effect in accelerating the pathogenesis of her
      moyamoya disease remains unknown. 1.

PMID- 30093456
TI  - Effects of Enzyme Replacement Therapy and Antidrug Antibodies in Patients with
      Fabry Disease.

PMID- 30093461
TI  - Non-invasive treatment of pyogenic granuloma by using Nd:YAG laser.
AB  - Pyogenic granuloma is a 'reactive lesion' in the oral cavity caused due to
      hormonal imbalance or poor oral hygiene. There are different methods to excise
      this lesion but most successful is treatment with lasers. Currently, there are
      different lasers available commercially and are used by clinicians to excise this
      lesion. In this case report, a 20-year-old female patient reported to the
      department with a complaint of overgrowth of gingiva on lower canine. It was
      excised by using neodymium-doped yttrium aluminium garnet laser and the patient
      was asked for regular follow-up after 1 week and 6 months. The excised lesion was
      sent to pathology where the lesion was confirmed to be pyogenic granuloma. The
      patient reported no pain, no blood loss during or postsurgery. Laser is a useful
      technique for excisional surgeries; it is safe, effective and reduces time of
      treatment as well as time of healing.

PMID- 30093463
TI  - Arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome: a rare
      association with high GGT level and absent kidney.
AB  - We report a case of a term baby presenting with neonatal cholestasis and upper
      limb flexion deformity on day 4 of life. On further evaluation, high gamma
      glutamyl transpeptidase (GGT) levels and absent left kidney were found. A
      diagnosis of arthrogryposis, renal dysfunction and cholestasis (ARC) syndrome was
      made which is a rare autosomal recessive disorder with primarily clinical
      diagnosis. Outcome of this condition is dismal. It has a large spectrum of
      clinical manifestations, but association with high GGT levels and absent kidney
      is quite rare. No single case report has observed such an association, and this
      is the first case of ARC syndrome reported from India to the best of our
      knowledge.

PMID- 30093462
TI  - Eosinophilic angiocentric fibrosis : a sino-orbital masquerader.
AB  - A 58-year-old Caucasian male presented with left periorbital oedema extending to
      the nasal area for 1 year along with nasal discharge for 1 month. Lab work was
      significant for positive cytoplasmic antineutrophil cytoplasmic antibodies. CT
      scan showed solid mass along the nasal soft tissue with bony nasal destruction. A
      CT scan of the thorax was performed to rule out granulomatosis with polyangiitis
      and showed multiple pulmonary nodules. Biopsies of the nasal mass and lung nodule
      were performed which showed fragments of fibrosis with spindle cell proliferation
      consistent with eosinophilic angiocentric fibrosis (EAF). EAF is a very rare
      disease, recently described as a subtype of immunoglobulin G4-related disease. A
      few rare cases of EAF involving the structures of the orbit have been reported in
      the literature.

PMID- 30093464
TI  - Renal germ cell metastatic tumour with rupture, bleeding and syncope: an unusual
      clinical presentation in a young patient.
AB  - The most common malignancy in young men is a germ cell tumour of the testes.
      Metastatic renal disease is relatively uncommon and usually manifests in the
      retroperitoneal lymph nodes. Visceral metastases to the liver, and metastases to
      the lungs and the brain are more common. Few large studies characterising
      patients with germ cell tumours and associated renal metastases have yet been
      published. We report an unusual case of successful management, through demolitive
      surgery, of a 22-year-old male patient affected by spontaneous intrarenal rupture
      of metastases secondary to testicular cancer. The patient was admitted to our
      urology department due to recurrent episodes of haematuria and clinical symptoms
      of persistent hypotension.

PMID- 30093465
TI  - Acupuncture treatment for dysfunctional uterine bleeding in an adolescent.
AB  - A 17-year-old girl with a history of dysfunctional uterine bleeding (DUB) and
      severe dysmenorrhoea was treated with different conventional hormonal therapies
      for 16 months without improvement.Treatment with traditional Chinese acupuncture
      was started while she was taking oral contraceptives. She received a total of 27
      treatments in 17 weeks. Her menstrual cycle normalised after 4 weeks (10
      treatments). She continued to be regular during the rest of treatments and to
      date, 6 months after the treatment was discontinued. This report summarises the
      acupuncture treatment for DUB in this adolescent girl.

PMID- 30093467
TI  - Hydatid cyst of the neck mimicking a branchial cleft cyst.
AB  - Here we report a rare case of primary hydatid cyst with involvement of soft
      tissue of the neck in a child. A 4-year-old girl presented with gradual swelling
      of the right side of her neck over a period of several months. The lump was
      fairly soft and painless with no significant inflammation. There was no other
      abnormal finding in the physical examination. Imaging was performed by
      ultrasonography followed by neck CT scan which demonstrated a simple cyst as the
      cause for the neck bulging. With the presumed diagnosis of a branchial cleft
      cyst, surgical resection was performed. Hydatid cyst was confirmed in pathology.
      Isolated soft-tissue hydatid cyst is an uncommon finding which should be
      considered in the differential diagnosis of soft-tissue cystic lesions especially
      in endemic regions. This is of more significance in children in whom congenital
      cysts of head and neck are more common.

PMID- 30093466
TI  - Adult Henolch-Schonlein purpura: multiorgan failure in the setting of a purpuric
      rash.
AB  - We report a 66-year-old man with a history of congestive heart failure, atrial
      fibrillation on warfarin therapy and chronic kidney disease that presented with
      acute dyspnoea. He had multiple palpable purpuric lesions on his bilateral lower
      extremities. Laboratory findings supported acute anaemia with no obvious bleeding
      source, supratherapeutic international normalised ratio and acute on chronic
      kidney injury. Oesophogastroduodenoscopy and colonoscopy initially suggested
      ischaemic colitis. The patient's legs were treated symptomatically with topical
      steroids. He later developed acute large volume bloody diarrhoea that made him
      haemodynamically unstable. Punch biopsy of the skin was consistent with
      leucocytoclastic vasculitis and direct immunofluorescence demonstrated
      immunoglobulin A and C3 deposits consistent with Henoch-Schonlein purpura. The
      patient was treated with oral steroids. Bleeding stabilised and rash resolved.
      Steroids were successfully tapered. The patient was discharged on haemodialysis
      but ultimately this was able to be discontinued.

PMID- 30093468
TI  - A rare case of incarcerated femoral hernia containing small bowel and appendix.
AB  - An 81-year-old woman was admitted under the acute medical team with a significant
      acute kidney injury secondary to presumed gastroenteritis, following a 5-day
      history of diarrhoea and vomiting. She continued to deteriorate despite
      resuscitative efforts. Subsequently, a non-contrast CT scan revealed likely small
      bowel obstruction second to a Richter's hernia in the inguinal canal. At
      diagnostic laparoscopy, both small bowel and appendix were identified to be
      incarcerated within the right femoral canal. The patient recovered uneventfully
      and was safely discharged several days following a laparoscopic appendicectomy
      and right femoral hernia repair.

PMID- 30093469
TI  - Acute serous tamponade after paraesophageal hernia repair reoperation.
AB  - Cardiac tamponade is a common complication after cardiac surgery and is usually
      caused by bleeding or thrombus in the early postoperative period. Postoperative
      serous tamponade is more rare and usually of gradual onset. We report an unusual
      and life-threatening case of serous tamponade occurring on postoperative day 1
      following a third-time paraesophageal hernia repair.

PMID- 30093470
TI  - Follow-up of water-only fasting and an exclusively plant food diet in the
      management of stage IIIa, low-grade follicular lymphoma.

PMID- 30093471
TI  - Spontaneous ovarian heterotopic pregnancy.
AB  - Heterotopic pregnancy is a simultaneous intrauterine and ectopic pregnancy. We
      report a case of a spontaneous ovarian heterotopic pregnancy. A 36-year-old
      woman, gravida 7 para 4-1-1-5 at 4 weeks gestation (spontaneous conception),
      presented to the emergency department with vaginal spotting, lower abdominal
      cramps with human chorionic gonadotropin(hCG) 10 772 mIU/mL (hCG at T0).
      Abdominal and pelvic examinations were benign. Transvaginal sonogram (TVS) showed
      an intrauterine gestational sac and yolk sac, no fetal pole visualised. She was
      discharged home with a diagnosis of threatened abortion. The patient returned to
      the emergency department 3 weeks later (T1) at 7 weeks gestation with recurrent
      vaginal bleeding and lower abdominal pain. Her TVS showed an empty uterus with
      small amount of free fluid in the cul-de-sac. A small 2 cm round mass noted in
      the adnexa with hCG of 4663 mIU/mL (hCG at T1). Laparoscopy revealed normal
      fallopian tubes bilaterally and a ruptured right ovarian ectopic pregnancy.
      Pathology was consistent with ectopic pregnancy. Abnormal hCG patterns should
      raise suspicion for heterotopic pregnancy.

PMID- 30093472
TI  - Hepatic angiosarcoma as a cause of acute liver failure.
AB  - Hepatic angiosarcoma is an extremely rare disease entity that accounts for
      approximately 0.1%-2% of primary liver malignancy. It is three times more common
      in men than women and usually affects the former in their sixth or seventh decade
      of life. Risk factors for the development of hepatic angiosarcoma include the use
      of oral contraceptives, exposure to anabolic steroids, radiation, thorium
      dioxide, arsenic and vinyl chloride. The prognosis of hepatic angiosarcoma is
      extremely poor which is attributable to early metastases to other organs,
      resistance to traditional chemotherapy and radiotherapy regimens and rapid
      progression of the tumour. Optimal management of patients is poorly demarcated
      due to the rarity of the tumour. We present a case series of two patients: one
      who passed away due to acute hepatic failure secondary to hepatic angiosarcoma
      and the second who underwent a liver transplantation and was subsequently
      diagnosed with hepatic angiosarcoma based on his explant histology.

PMID- 30093473
TI  - Synchronous colon cancer with pulmonary metastasis and follicular variant of
      papillary thyroid cancer metastasising to kidney.
AB  - Thyroid malignancies are one of the fastest growing cancers in the world, with
      the majority being papillary thyroid cancer. Follicular variant of papillary
      thyroid cancer accounts for about 10%-20% of papillary thyroid carcinomas. The
      usual sites for metastases of these tumours are lungs and bones with renal
      metastases being extremely rare. We describe a case of a 64-year-old woman who
      presented with abdominal pain. On subsequent imaging, she was found to have a
      colonic mass with metastatic lesions in the lungs and tumour involving left
      kidney. On biopsy and immunohistochemical staining, the renal mass showed
      positivity for thyroid cancer markers. Thyroid scan was noted to be negative and
      the patient was placed on active surveillance after undergoing chemotherapy for
      colonic adenocarcinoma.

PMID- 30093474
TI  - Spontaneous coronary artery dissection in a man with intense coughing spasms.
AB  - Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial
      infarction of emerging significance, which occurs predominantly in young women
      without coronary artery disease risk factors. Valsalva-like activities such as
      coughing have been identified as potential triggers for the development of SCAD.
      We report a case of SCAD in a man in whom the only identifiable predisposing
      factor was excessive coughing. He presented with atypical chest pain. Troponin I
      peaked at 29 ng/mL, and ECG showed no evidence of ischaemic changes. He underwent
      cardiac catheterisation via the radial approach, which revealed a linear second
      obtuse marginal dissection. He was managed conservatively with medical therapy
      with a good outcome.

PMID- 30093475
TI  - Innocent PET avidity in patient with metastatic melanoma.

PMID- 30093476
TI  - Auto-amputation of penis due to advanced carcinoma penis.

PMID- 30093477
TI  - Gadolinium Deposition within the Pediatric Brain: No Increased Intrinsic T1
      Weighted Signal Intensity within the Dentate Nucleus following the Administration
      of a Minimum of 4 Doses of the Macrocyclic Agent Gadoteridol.
AB  - BACKGROUND AND PURPOSE: Our aim was to evaluate whether serial administration of
      the macrocyclic gadolinium-based contrast agent gadoteridol in children is
      associated with T1-weighted hyperintensity within the dentate nucleus, an imaging
      surrogate for gadolinium deposition. MATERIALS AND METHODS: We identified a
      retrospective cohort of 10 patients younger than 18 years of age who underwent
      between 4 and 8 gadoteridol-enhanced MR imaging examinations of the brain from
      2016 to 2017. For comparison, we identified a retrospective cohort of 9 pediatric
      patients who each underwent 6 gadodiamide-enhanced MR imaging examinations. For
      each examination, both dentate nuclei were contoured on unenhanced images and the
      mean dentate-to-pons signal intensity ratio was calculated. Dentate-to-pons
      signal intensity ratios from the first and last scans were compared using paired
      t tests. RESULTS: In the gadoteridol group, there was no significant change in
      the mean dentate-to-pons signal intensity ratio from the first to the last scan
      (0.99 versus 0.99, P = .59). In the gadodiamide group, there was a significant
      increase in the mean dentate-to-pons signal intensity ratio from the first to the
      last scan (0.99 versus 1.10, P = .001). CONCLUSIONS: Repeat administration of the
      macrocyclic gadolinium-based contrast agent gadoteridol in children was not
      associated with T1-weighted dentate hyperintensity, while the repeat
      administration of the linear gadolinium-based contrast agent gadodiamide was
      associated with T1-weighted dentate hyperintensity, presumably due to gadolinium
      deposition.

PMID- 30093478
TI  - Brachial Plexus Ultrasound and MRI in Children with Brachial Plexus Birth Injury.
AB  - BACKGROUND AND PURPOSE: Brachial plexus birth injury is caused by traction on the
      neck during delivery and results in flaccid palsy of an upper extremity commonly
      involving C5-C6 nerve roots. MR imaging and MR myelography help to assess the
      anatomic location, extent, and severity of brachial plexus injuries which
      influence the long-term prognosis along with the surgical decision making.
      Recently, sonography has been increasingly used as the imaging modality of choice
      for brachial plexus injuries. The aim of this study was to assess the degree of
      correlation among brachial plexus sonography, MR imaging, and surgical findings
      in children with brachial plexus birth injury. MATERIALS AND METHODS: This
      prospective study included 55 consecutive patients (girls/boys = 32:23; mean age,
      2.1 +/- 0.8 months) with brachial plexus birth injury between May 2014 and April
      2017. The patients were classified according to the Narakas classification and
      were followed up at 4- to 6-week intervals for recovery by the Modified Mallet
      system and sonography without specific preparation for evaluation. All patients
      had MR imaging under general anesthesia. Nerve root avulsion-retraction,
      pseudomeningocele, and periscalene soft tissue were accepted brachial plexus
      injury findings on imaging. Interobserver agreement for MR imaging and the
      agreement between imaging and surgical findings were estimated using the kappa
      statistic. The diagnostic accuracy of sonography and MR imaging was calculated on
      the basis of the standard reference, which was the surgical findings. RESULTS:
      Forty-three patients had pre- and postganglionic injury, 12 had only
      postganglionic injury findings, and 47% of patients underwent an operation. On
      sonography, no patients had preganglionic injury, but all patients had
      postganglionic injury findings. For postganglionic injury, the concordance rates
      between imaging and the surgical findings ranged from 84% to 100%, and the
      diagnostic accuracy of sonography and MR imaging was 89% and 100%, respectively.
      For preganglionic injury, the diagnostic accuracy of MR imaging was 92%.
      Interobserver agreement and the agreement between imaging and the surgical
      findings were almost perfect for postganglionic injury (kappa = 0.81-1, P <
      .001). CONCLUSIONS: High-resolution sonography can identify and locate the
      postganglionic injury associated with the upper and middle trunks. The ability of
      sonography to evaluate pre- and the postganglionic injury associated with the
      lower trunk was quite limited. Sonography can be used as a complement to MR
      imaging; thus, the duration of the MR imaging examination and the need for
      sedation can be reduced by sonography.

PMID- 30093480
TI  - Investigation of a New Version of the Liquid Embolic Agent PHIL with Extra-Low
      Viscosity in an Endovascular Embolization Model.
AB  - BACKGROUND AND PURPOSE: The type and composition of an embolic agent have a
      relevant influence on the performance of endovascular embolization. The aim of
      this study was to investigate a new version of the liquid embolic agent
      precipitating hydrophobic injectable liquid (PHIL) with extra-low-viscosity in an
      in vivo embolization model. MATERIALS AND METHODS: Twenty-four embolization
      procedures were performed in the porcine rete mirabile. Eight embolizations were
      performed with PHIL 25% low viscosity, Squid 12, and standard PHIL 25%,
      respectively. Procedure time, required volume of embolic agent, visibility of the
      embolic agent, embolization control, embolization extent (ie, penetration of the
      rete mirabile), amount of reflux, and degree of embolization distal to the rete
      mirabile were assessed. RESULTS: All embolic agents were adequately visible. The
      embolization extent was not significantly different among the 3 investigated
      agents; however, there was a tendency toward a higher embolization extent for
      PHIL 25% low viscosity (median embolization extent: 88% [PHIL 25% low viscosity];
      65% [Squid 12]; 60% [PHIL 25%]; P = .146). The amount of reflux was significantly
      lower for the extra-low-viscosity agents PHIL 25% low viscosity and Squid 12
      compared with the standard PHIL 25% (median reflux distance: 8 mm [PHIL 25% low
      viscosity]; 6 mm [Squid 12]; 17 mm [PHIL 25%]; P = .011). All other embolization
      features did not differ among agents. CONCLUSIONS: PHIL 25% low viscosity is a
      promising liquid embolic agent for endovascular embolization, featuring effective
      distal penetration, adequate visibility, a low amount of reflux, and good flow
      control.

PMID- 30093479
TI  - Comparison of a Photon-Counting-Detector CT with an Energy-Integrating-Detector
      CT for Temporal Bone Imaging: A Cadaveric Study.
AB  - BACKGROUND AND PURPOSE: Evaluating abnormalities of the temporal bone requires
      high-spatial-resolution CT imaging. Our aim was to assess the performance of
      photon-counting-detector ultra-high-resolution acquisitions for temporal bone
      imaging and compare the results with those of energy-integrating-detector ultra
      high-resolution acquisitions. MATERIALS AND METHODS: Phantom studies were
      conducted to quantify spatial resolution of the ultra-high-resolution mode on a
      prototype photon-counting-detector CT scanner and an energy-integrating-detector
      CT scanner that uses a comb filter. Ten cadaveric temporal bones were scanned on
      both systems with the radiation dose matched to that of the clinical
      examinations. Images were reconstructed using a sharp kernel, 0.6-mm (minimum)
      thickness for energy-integrating-detector CT, and 0.6- and 0.25-mm (minimum)
      thicknesses for photon-counting-detector CT. Image noise was measured and
      compared using adjusted 1-way ANOVA. Images were reviewed blindly by 3
      neuroradiologists to assess the incudomallear joint, stapes footplate, modiolus,
      and overall image quality. The ranking results for each specimen and protocol
      were compared using the Friedman test. The Krippendorff alpha was used for
      interreader agreement. RESULTS: Photon-counting-detector CT showed an increase of
      in-plane resolution compared with energy-integrating-detector CT. At the same
      thickness (0.6 mm), images from photon-counting-detector CT had significantly
      lower (P < .001) image noise compared with energy-integrating-detector CT.
      Readers preferred the photon-counting-detector CT images to the energy
      integrating-detector images for all 3 temporal bone structures. A moderate
      interreader agreement was observed with the Krippendorff alpha = 0.50. For
      overall image quality, photon-counting-detector CT image sets were ranked
      significantly higher than images from energy-integrating-detector CT (P < .001).
      CONCLUSIONS: This study demonstrated substantially better delineation of fine
      anatomy for the temporal bones scanned with the ultra-high-resolution mode of
      photon-counting-detector CT compared with the ultra-high-resolution mode of a
      commercial energy-integrating-detector CT scanner.

PMID- 30093481
TI  - Reply.

PMID- 30093482
TI  - Adjunctive Efficacy of Intra-Arterial Conebeam CT Angiography Relative to DSA in
      the Diagnosis and Surgical Planning of Micro-Arteriovenous Malformations.
AB  - BACKGROUND AND PURPOSE: Micro-arteriovenous malformations are an underrecognized
      etiology of intracranial hemorrhage. Our study aimed to assess the adjunctive
      efficacy of intra-arterial conebeam CTA relative to DSA in the diagnosis and
      surgical planning of intracranial micro-AVMs. MATERIALS AND METHODS: We performed
      a retrospective study of all micro-AVMs (<=1-cm nidus) at our institution.
      Blinded neuroradiologists qualitatively graded DSA and intra-arterial conebeam
      CTA images for the detection of specific micro-AVM anatomic parameters (arterial
      feeder, micronidus, and venous drainer) and defined an overall diagnostic value.
      Statistical and absolute differences in the overall diagnostic values defined the
      relative intra-arterial conebeam CTA diagnostic values, respectively. Blinded
      neurosurgeons reported their treatment approach after DSA and graded the
      adjunctive value of intra-arterial conebeam CTA to improve or modify treatment.
      Intra-arterial conebeam CTA efficacy was defined as interobserver agreement in
      the relative intra-arterial conebeam CTA diagnostic and/or treatment-planning
      value scores. RESULTS: Ten patients with micro-AVMs presented with neurologic
      deficits and/or intracranial hemorrhages. Both neuroradiologists assigned a
      higher overall intra-arterial conebeam CTA diagnostic value (P < .05), secondary
      to improved evaluation of both arterial feeders and the micronidus, with good
      interobserver agreement (tau = 0.66, P = .018) in the relative intra-arterial
      conebeam CTA diagnostic value. Both neurosurgeons reported that integrating the
      intra-arterial conebeam CTA data into their treatment plan would allow more
      confident localization for surgical/radiation treatment (8/10; altering the
      treatment plan in 1 patient), with good interobserver agreement in the relative
      intra-arterial conebeam CTA treatment planning value (tau = 0.73, P = .025).
      CONCLUSIONS: Adjunctive intra-arterial conebeam CTA techniques are more effective
      in the diagnostic identification and anatomic delineation of micro-AVMs, relative
      to DSA alone, with the potential to improve microsurgical or radiosurgery
      treatment planning.

PMID- 30093483
TI  - Evaluation of Thick-Slab Overlapping MIP Images of Contrast-Enhanced 3D T1
      Weighted CUBE for Detection of Intracranial Metastases: A Pilot Study for
      Comparison of Lesion Detection, Interpretation Time, and Sensitivity with
      Nonoverlapping CUBE MIP, CUBE, and Inversion-Recovery-Prepared Fast-Spoiled
      Gradient Recalled Brain Volume.
AB  - BACKGROUND AND PURPOSE: Early and accurate identification of cerebral metastases
      is important for prognostication and treatment planning although this process is
      often time consuming and labor intensive, especially with the hundreds of images
      associated with 3D volumetric imaging. This study aimed to evaluate the benefits
      of thick-slab overlapping MIPs constructed from contrast-enhanced T1-weighted
      CUBE (overlapping CUBE MIP) for the detection of brain metastases in comparison
      with traditional CUBE and inversion-recovery prepared fast-spoiled gradient
      recalled brain volume (IR-FSPGR-BRAVO) and nonoverlapping CUBE MIP. MATERIALS AND
      METHODS: A retrospective review of 48 patients with cerebral metastases was
      performed at our institution from June 2016 to October 2017. Brain MRIs, which
      were acquired on multiple 3T scanners, included gadolinium-enhanced T1-weighted
      IR-FSPGR-BRAVO and CUBE, with subsequent generation of nonoverlapping CUBE MIP
      and overlapping CUBE MIP. Two blinded radiologists identified the total number
      and location of metastases on each image type. The Cohen kappa was used to
      determine interrater agreement. Sensitivity, interpretation time, and lesion
      contrast-to-noise ratio were assessed. RESULTS: Interrater agreement for
      identification of metastases was fair-to-moderate for all image types (kappa =
      0.222-0.598). The total number of metastases identified was not significantly
      different across the image types. Interpretation time for CUBE MIPs was
      significantly shorter than for CUBE and IR-FSPGR-BRAVO, saving at least 50
      seconds per case on average (P < .001). The mean lesion contrast-to-noise ratio
      for both CUBE MIPs was higher than for IR-FSPGR-BRAVO. The mean contrast-to-noise
      ratio for small lesions (<4 mm) was lower for nonoverlapping CUBE MIP (1.55) than
      for overlapping CUBE MIP (2.35). For both readers, the sensitivity for lesion
      detection was high for all image types but highest for overlapping CUBE MIP and
      CUBE (0.93-0.97). CONCLUSIONS: This study suggests that the use of overlapping
      CUBE MIP or nonoverlapping CUBE MIP for the detection of brain metastases can
      reduce interpretation time without sacrificing sensitivity, though the contrast
      to-noise ratio of lesions is highest for overlapping CUBE MIP.

PMID- 30093485
TI  - Simultaneous Bipedicular Radiofrequency Ablation Combined with Vertebral
      Augmentation for Local Tumor Control of Spinal Metastases.
AB  - BACKGROUND AND PURPOSE: Percutaneous radiofrequency ablation combined with
      vertebral augmentation has emerged as a minimally invasive treatment for patients
      with vertebral metastases who do not respond to or have contraindications to
      radiation therapy. The prevalence of posterior vertebral body metastases presents
      access and treatment challenges in the unique anatomy of the spine. The purpose
      of this study was to evaluate the safety and efficacy of simultaneous bipedicular
      radiofrequency ablation using articulating bipolar electrodes combined with
      vertebral augmentation for local tumor control of spinal metastases. MATERIALS
      AND METHODS: Imaging-guided simultaneous bipedicular radiofrequency ablation
      combined with vertebral augmentation was performed in 27 patients (33 tumors)
      with vertebral metastases selected following multidisciplinary consultations, to
      achieve local tumor control in this retrospective study. Tumor characteristics,
      procedural details, and complications were documented. Pre- and postprocedural
      cross-sectional imaging was evaluated to assess local tumor control rates.
      RESULTS: Thirty-three tumors were successfully ablated in 27 patients. Posterior
      vertebral body or pedicle involvement or both were present in 94% (31/33) of
      cases. Sixty-seven percent (22/33) of the tumors involved >=75% of the vertebral
      body volume. Posttreatment imaging was available for 79% (26/33) of the treated
      tumors. Local tumor control was achieved in 96% (25/26) of tumors median imaging
      follow up of 16 weeks. No complications were reported, and no patients had
      clinical evidence of metastatic spinal cord compression at the treated levels.
      CONCLUSIONS: Simultaneous bipedicular radiofrequency ablation combined with
      vertebral augmentation is safe and effective for local tumor control of vertebral
      metastases. Articulating bipolar electrodes enable the placement and proximity
      necessary for optimal confluence of the ablation zones. Local tumor control may
      lead to more durable pain palliation, prevent disease progression, and reduce
      skeletal-related events of the spine.

PMID- 30093486
TI  - Blunt Cerebrovascular Injuries: Advances in Screening, Imaging, and Management
      Trends.

PMID- 30093487
TI  - PDA Forms Journal Editorial Board - Call for Volunteeers.

PMID- 30093484
TI  - Quantitative MRI of Perivascular Spaces at 3T for Early Diagnosis of Mild
      Cognitive Impairment.
AB  - BACKGROUND AND PURPOSE: The limitations inherent in the current methods of
      diagnosing mild cognitive impairment have constrained the use of early
      therapeutic interventions to delay the progression of mild cognitive impairment
      to dementia. This study evaluated whether quantifying enlarged perivascular
      spaces observed on MR imaging can help differentiate those with mild cognitive
      impairment from cognitively healthy controls and, thus, have an application in
      the diagnosis of mild cognitive impairment. MATERIALS AND METHODS: We automated
      the identification of enlarged perivascular spaces in brain MR Images using a
      custom quantitative program designed with Matlab. We then quantified the
      densities of enlarged perivascular spaces for patients with mild cognitive
      impairment (n = 14) and age-matched cognitively healthy controls (n = 15) and
      compared them to determine whether the density of enlarged perivascular spaces
      can serve as an imaging surrogate for mild cognitive impairment diagnosis.
      RESULTS: Quantified as a percentage of volume fraction (v/v%), densities of
      enlarged perivascular spaces were calculated to be 2.82 +/- 0.40 v/v% for
      controls and 4.17 +/- 0.57 v/v% for the mild cognitive impairment group in the
      subcortical brain (P < .001), and 2.74 +/- 0.57 v/v% for the controls and 3.90 +/
      0.62 v/v% for the mild cognitive impairment cohort in the basal ganglia (P <
      .001). Maximum intensity projections exhibited a visually conspicuous difference
      in the distributions of enlarged perivascular spaces for a patient with mild
      cognitive impairment and a control patient. By means of receiver operating
      characteristic curve analysis, we determined the sensitivity and specificity of
      using enlarged perivascular spaces as a differentiating biomarker between mild
      cognitive impairment and controls to be 92.86% and 93.33%, respectively.
      CONCLUSIONS: The density of enlarged perivascular spaces was found to be
      significantly higher in those with mild cognitive impairment compared with age
      matched healthy control subjects. The density of enlarged perivascular spaces,
      therefore, may be a useful imaging biomarker for the diagnosis of mild cognitive
      impairment.

PMID- 30093488
TI  - Serum anti-Mullerian hormone predicts ovarian response in (Macaca fascicularis)
      monkeys.
AB  - AMH as an accurate predictor of ovarian response has been studied extensively in
      women undergoing assisted reproductive technology treatment, but little is known
      about its prediction value in monkeys undergoing ovarian stimulation. In current
      study, a total of 380 cynomolgus monkeys ranging from 5 to 12 yr received 699
      ovarian stimulation cycles. Serum samples were collected for AMH measure with
      enzyme-linked immunosorbent assay. It was found that serum AMH levels were
      positive correlated with the number of retrieved oocytes (p<0.01) in the first,
      second and third stimulation cycles. In the first cycles, area under the curve
      (ROCAUC) of AMH is 0.688 for low response and 0.612 for high response
      respectively, indicating the significant prediction values (p=0.000 and p=0.005).
      The optimal AMH cut-off value was 9.68 ng/ml for low ovarian response, and 15.88
      ng/ml for high ovarian response prediction. In the second stimulation cycles, the
      significance of ROCAUC of AMH for high response rather than the low response was
      observed (p=0.001 and p=0.468). The optimal AMH cut-off value for high ovarian
      response was 15.61 ng/ml. In the third stimulation cycles, AMH lost the
      prediction value with no significant ROCAUC. Our data demonstrated that AMH, not
      age, is a cycle dependent predictor for ovarian response in form of oocyte
      yields, which would promote the application of AMH in assisted reproductive
      treatment (ART) of female cynomolgus monkeys. AMH evaluation would optimize
      candidate selection for ART and individualize the ovarian stimulation strategies,
      and consequentially improve the efficiency in monkeys.

PMID- 30093489
TI  - Protein-RNA interactions: structural characteristics and hotspot amino acids.
AB  - Structural information about protein-RNA complexes supports the understanding of
      crucial recognition processes in the cell, and it can allow the development of
      high affinity ligands to interfere with these processes. In this respect, the
      identification of amino acid hotspots is particularly important. In contrast to
      protein-protein interactions, in silico approaches for protein-RNA interactions
      lag behind in their development. Herein, we report an analysis of available
      protein-RNA structures. We assembled a data set of 322 crystal and NMR structures
      and analyzed them regarding interface properties. In addition, we describe a
      computational alanine-scanning approach which provides interaction scores for
      interface amino acids, allowing the identification of potential hotspots in
      protein-RNA interfaces. We have made the computational approach available as an
      online tool, which allows interaction scores to be calculated for any structure
      of a protein-RNA complex by uploading atomic coordinates to the PRI HotScore web
      server (https://pri-hotscore.labs.vu.nl).

PMID- 30093490
TI  - Rat BodyMap transcriptomes reveal unique circular RNA features across tissue
      types and developmental stages.
AB  - Circular RNAs (circRNAs) are a novel class of regulatory RNAs. Here, we present a
      comprehensive investigation of circRNA expression profiles across 11 tissues and
      four developmental stages in rats, along with cross-species analyses in humans
      and mice. Although the expression of circRNAs is positively correlated with that
      of cognate mRNAs, highly expressed genes tend to splice a larger fraction of
      circular transcripts. Moreover, circRNAs exhibit higher tissue specificity than
      cognate mRNAs. Intriguingly, while we observed a monotonic increase of circRNA
      abundance with age in the rat brain, we further discovered a dynamic, age
      dependent pattern of circRNA expression in the testes that is characterized by a
      dramatic increase with advancing stages of sexual maturity and a decrease with
      aging. The age-sensitive testicular circRNAs are highly associated with
      spermatogenesis, independent of cognate mRNA expression. The tissue/age
      implications of circRNAs suggest that they present unique physiological functions
      rather than simply occurring as occasional by-products of gene transcription.

PMID- 30093491
TI  - Enriched environment enhances beta-adrenergic signaling to prevent microglia
      inflammation by amyloid-beta.
AB  - Environmental enrichment (EE) is a rodent behavioral paradigm that can model the
      cognitive benefits to humans associated with intellectual activity and exercise.
      We recently discovered EE's anti-inflammatory protection of brain microglia
      against soluble oligomers of human amyloid beta-protein (oAbeta).
      Mechanistically, we report that the key factor in microglial protection by EE is
      chronically enhanced beta-adrenergic signaling. Quantifying microglial morphology
      and inflammatory RNA profiles revealed that mice in standard housing (SH) fed the
      beta-adrenergic agonist isoproterenol experienced similar protection of microglia
      against oAbeta-induced inflammation as did mice in EE Conversely, mice in EE fed
      the beta-adrenergic antagonist propranolol lost microglial protection against
      oAbeta. Mice lacking beta1/beta2-adrenergic receptors showed no protection of
      microglia by EE In SH mice, quantification of norepinephrine in hippocampus and
      interstitial fluid showed that oAbeta disrupted norepinephrine homeostasis, and
      microglial-specific analysis of beta2-adrenergic receptors indicated a decreased
      receptor level. Both features were rescued by EE Thus, enhanced beta-adrenergic
      signaling at the ligand and receptor levels mediates potent benefits of EE on
      microglial inflammation induced by human Abeta oligomers in vivo.

PMID- 30093492
TI  - microRNAs selectively protect hub cells of the germline stem cell niche from
      apoptosis.
AB  - Genotoxic stress such as irradiation causes a temporary halt in tissue
      regeneration. The ability to regain regeneration depends on the type of cells
      that survived the assault. Previous studies showed that this propensity is
      usually held by the tissue-specific stem cells. However, stem cells cannot
      maintain their unique properties without the support of their surrounding niche
      cells. In this study, we show that exposure of Drosophila melanogaster to
      extremely high levels of irradiation temporarily arrests spermatogenesis and
      kills half of the stem cells. In marked contrast, the hub cells that constitute a
      major component of the niche remain completely intact. We further show that this
      atypical resistance to cell death relies on the expression of certain
      antiapoptotic microRNAs (miRNAs) that are selectively expressed in the hub and
      keep the cells inert to apoptotic stress signals. We propose that at the tissue
      level, protection of a specific group of niche cells from apoptosis underlies
      ongoing stem cell turnover and tissue regeneration.

PMID- 30093494
TI  - Genome-wide CRISPR screen identifies TMEM41B as a gene required for autophagosome
      formation.
AB  - Macroautophagy is an intracellular degradation process that requires multiple
      autophagy-related (ATG) genes. In this study, we performed a genome-wide screen
      using the autophagic flux reporter GFP-LC3-RFP and identified TMEM41B as a novel
      ATG gene. TMEM41B is a multispanning membrane protein localized in the
      endoplasmic reticulum (ER). It has a conserved domain also found in vacuole
      membrane protein 1 (VMP1), another ER multispanning membrane protein essential
      for autophagy, yeast Tvp38, and the bacterial DedA family of putative half
      transporters. Deletion of TMEM41B blocked the formation of autophagosomes at an
      early step, causing accumulation of ATG proteins and small vesicles but not
      elongating autophagosome-like structures. Furthermore, lipid droplets accumulated
      in TMEM41B-knockout (KO) cells. The phenotype of TMEM41B-KO cells resembled those
      of VMP1-KO cells. Indeed, TMEM41B and VMP1 formed a complex in vivo and in vitro,
      and overexpression of VMP1 restored autophagic flux in TMEM41B-KO cells. These
      results suggest that TMEM41B and VMP1 function together at an early step of
      autophagosome formation.

PMID- 30093496
TI  - Abdominal compartment syndrome secondary to megarectum and megasigmoid.
AB  - A 31-year-old male patient with chronic constipation of unknown aetiology
      presented emergently with worsening nausea, vomiting and abdominal distension of
      one week duration. On examination, his abdomen was distended with minimal
      tenderness. A plain film of the abdomen demonstrated severe faecal loading. The
      patient was haemodynamically unstable on admission and appeared sick. An urgent
      CT abdomen and pelvis was conducted showing extensive rectal dilatation and
      associated proximal colonic stercoral perforation. The patient proceeded straight
      to theatre for laparotomy as his general condition was deteriorating rapidly. On
      transfer to the operating table, the patient suffered cardiopulmonary arrest.
      Resuscitation was immediately commenced. Abdominal compartment syndrome was
      suspected. Cardiac output was re-established following a midline laparotomy which
      acted relieve the abdominal pressure. The rectosigmoid faecal content was
      decompressed via an enterotomy. The perforated segment of transverse colon was
      resected and an end colostomy fashioned. A year later, the continuity of the
      bowel was re-established.

PMID- 30093493
TI  - VPS13A and VPS13C are lipid transport proteins differentially localized at ER
      contact sites.
AB  - Mutations in the human VPS13 genes are responsible for neurodevelopmental and
      neurodegenerative disorders including chorea acanthocytosis (VPS13A) and
      Parkinson's disease (VPS13C). The mechanisms of these diseases are unknown.
      Genetic studies in yeast hinted that Vps13 may have a role in lipid exchange
      between organelles. In this study, we show that the N-terminal portion of VPS13
      is tubular, with a hydrophobic cavity that can solubilize and transport
      glycerolipids between membranes. We also show that human VPS13A and VPS13C bind
      to the ER, tethering it to mitochondria (VPS13A), to late endosome/lysosomes
      (VPS13C), and to lipid droplets (both VPS13A and VPS13C). These findings identify
      VPS13 as a lipid transporter between the ER and other organelles, implicating
      defects in membrane lipid homeostasis in neurological disorders resulting from
      their mutations. Sequence and secondary structure similarity between the N
      terminal portions of Vps13 and other proteins such as the autophagy protein ATG2
      suggest lipid transport roles for these proteins as well.

PMID- 30093495
TI  - Queuosine-modified tRNAs confer nutritional control of protein translation.
AB  - Global protein translation as well as translation at the codon level can be
      regulated by tRNA modifications. In eukaryotes, levels of tRNA queuosinylation
      reflect the bioavailability of the precursor queuine, which is salvaged from the
      diet and gut microbiota. We show here that nutritionally determined Q-tRNA levels
      promote Dnmt2-mediated methylation of tRNA Asp and control translational speed of
      Q-decoded codons as well as at near-cognate codons. Deregulation of translation
      upon queuine depletion results in unfolded proteins that trigger endoplasmic
      reticulum stress and activation of the unfolded protein response, both in
      cultured human cell lines and in germ-free mice fed with a queuosine-deficient
      diet. Taken together, our findings comprehensively resolve the role of this
      anticodon tRNA modification in the context of native protein translation and
      describe a novel mechanism that links nutritionally determined modification
      levels to effective polypeptide synthesis and cellular homeostasis.

PMID- 30093497
TI  - Delayed Presentation of Isolated Adrenocorticotropin Insufficiency after
      Nivolumab Therapy for Advanced Non-small-cell lung carcinoma (NSCLC).
AB  - We describe a 73-year-old man who developed adrenal insufficiency 7 months after
      completing nivolumab therapy for advanced non-small cell lung cancer. He
      presented with non-specific symptoms of malaise and fatigue with an insidious
      13.6 kilogram weight loss, prompting an evaluation for disease progression, which
      was negative. Subsequent evaluation revealed isolated adrenocorticotropin
      insufficiency as the aetiology, attributed to a delayed side effect of nivolumab
      therapy.

PMID- 30093498
TI  - Retroperitoneal schwannoma misdiagnosed as an ovarian malignancy.
AB  - A 55-year-old woman presented to the hospital with abdominal discomfort over 3
      months. Contrast-enhanced abdominal CT showed a 10*9*6.5 cm sized well-defined
      solid-cystic enhancing mass in the right pelvic cavity. Under general
      anaesthesia, exploratory laparotomy was performed on suspicion of ovarian
      malignancy. Pathological examination revealed a retroperitoneal schwannoma with
      highly ordered cellular component (Antoni A) and hypocellularity with
      predominantly loose myxoid component (Antoni B). On immunohistochemical staining,
      the sample showed typically positive result for S-100 in the cytoplasm of the
      tumour cells. Schwannomas are consisting only of Schwann cells and are most often
      non-malignant tumors. It is relatively slow growing and usually located in the
      head, neck and the extremities. Schwannomas are quite rare in the retroperitoneal
      region. The diagnosis of retroperitoneal schwannomas is often delayed and
      misdiagnosed as an adnexal tumour, especially locating in the pelvic cavity.
      Surgical complete resection of tumour is the treatment of choice and recurrence
      is unusual after complete resection.

PMID- 30093499
TI  - Beer anaphylaxis due to coriander as hidden allergen.
AB  - Beer is one of the most widely consumed alcoholic beverage all over the world.
      Although the production and consumption of this beverage is diffuse, allergic
      reactions are very uncommonly reported, mainly due to wheat, yeast or hops
      allergy. More recently, many foods and drinks have been flavoured with spices,
      with a reported increase in allergic reactions. We report on a case of a young
      woman who experienced anaphylaxis due to coriander-flavoured beer. This is the
      first case of beer anaphylaxis due to coriander, which had been added to the beer
      as aromatising substance. As the presence of flavours is not always reported,
      they may be considered hidden allergens, whenever they are the cause of
      anaphylaxis to foods or beverages, the patient usually tolerated. In conclusion,
      allergic reactions to spices have to be considered in the patients with
      'idiopathic' anaphylaxis induced by common foods, where spices had been hidden.

PMID- 30093500
TI  - Spontaneous bone regeneration in a large haemophilic pseudotumour of mandible.
AB  - Pseudotumours of haemophilia (PTH) are locally expansile destructive haematomas
      which result in varying morbidity among haemophilic patients. Adequate
      haematological treatment and prophylaxis helps in preventing these haematomas.
      Currently, there is no uniform standard management protocol for this entity due
      to rarity of these lesions. PTH are seen in 1%-2% of the severe haemophilic
      patients. They may also be seen in moderate cases when adequate factor coverage
      is not provided or in cases with factor VIII inhibitors. We report a rare case of
      mandibular pseudotumour in a patient with moderate haemophilia and Glanzmann's
      thrombasthenia, treated successfully with decompression of the haematoma.
      Postdecompression, sequential radiography revealed spontaneous bone regeneration
      at the site of the lesion. With 2 years follow-up, the mandible had no residual
      lesion. This reveals the role and potential of conservative decompression even in
      cases with severe osteodestruction secondary to developing haematoma of the
      mandible in haemophilic patients.

PMID- 30093501
TI  - Trauma-induced dual vascular lesions in the liver-hepatic pseudoaneurysm with
      arteriohepatic venous fistula.

PMID- 30093502
TI  - Three-year outcomes after high hyperopia correction using photorefractive
      keratectomy with a large ablation zone.
AB  - AIM: To evaluate refractive and visual outcomes of photorefractive keratectomy
      (PRK) to treat high hyperopia using an aberration-neutral profile and large
      ablation zone. METHODS: This was a retrospective, consecutive observational case
      series at the Oftalmika Eye Hospital, Bydgoszcz, Poland. We included 51
      consecutive eyes of 34 patients who underwent alcohol-assisted PRK to correct
      hyperopia within the range of +3.6 to +6.15 D (mean+4.61+/-0.67 D). Procedures
      were performed with an Amaris 750S excimer laser (Schwind eye-tech-solutions
      GmbH, Kleinostheim, Germany) using an aberration-neutral profile and a 10 mm
      total ablation zone. Refractive results, predictability, safety and efficacy were
      evaluated 3 years postoperatively. RESULTS: At 1-year postsurgery, the mean
      manifest refraction spherical equivalent (MRSE) was -0.002+/-0.43 D and mean
      cylinder was -0.181+/-0.31 D, while the values were +0.09+/-0.46 D and -0.15+/
      0.26 D, respectively, at 2 years (MRSE p<0.001) and +0.15+/-0.44 D and -0.15+/
      0.26 D, respectively, at 3 years (MRSE p<0.001). 78% of eyes were within +/-0.50
      D of the attempted spherical equivalent correction. Three years postoperatively,
      22% of eyes lost one line of corrected distance visual acuity and 27% gained a
      line or two. The change in the mean corneal spherical aberrations for the 6 mm
      zone was from 0.27+/-0.07 to 0.08+/-0.13 um. CONCLUSIONS: High hyperopia
      correction with PRK using an aberration-neutral profile and large ablation zone
      provides good efficacy, safety, predictability and visual outcomes. Relatively
      low change of corneal spherical aberrations and low increase of hyperopia in the
      first three postoperative years were observed.

PMID- 30093504
TI  - CRISPR Causes Unexpected Genomic Damage.
AB  - A study in four cell lines concludes that CRISPR/Cas9 editing causes
      unanticipated genomic alterations, including large deletions, translocations, and
      insertions. Some of these changes could be the first hits that cause cells to
      eventually become neoplastic.

PMID- 30093503
TI  - Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That
      Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations.
AB  - The use of tyrosine kinase inhibitors (TKI) with activity against ALK, ROS1, or
      TRKA-C can result in significant clinical benefit in patients with diverse tumors
      harboring ALK, ROS1, or NTRK1-3 rearrangements; however, resistance invariably
      develops. The emergence of on-target kinase domain mutations represents a major
      mechanism of acquired resistance. Solvent-front substitutions such as ALKG1202R,
      ROS1G2032R or ROS1D2033N, TRKAG595R, and TRKCG623R are among the most
      recalcitrant of these mechanisms. Repotrectinib (TPX-0005) is a rationally
      designed, low-molecular-weight, macrocyclic TKI that is selective and highly
      potent against ROS1, TRKA-C, and ALK. Importantly, repotrectinib exhibits
      activity against a variety of solvent-front substitutions in vitro and in vivo As
      clinical proof of concept, in an ongoing first-in-human phase I/II trial,
      repotrectinib achieved confirmed responses in patients with ROS1 or NTRK3 fusion
      positive cancers who had relapsed on earlier-generation TKIs due to ROS1 or TRKC
      solvent-front substitution-mediated resistance.Significance: Repotrectinib (TPX
      0005), a next-generation ROS1, pan-TRK, and ALK TKI, overcomes resistance due to
      acquired solvent-front mutations involving ROS1, NTRK1-3, and ALK Repotrectinib
      may represent an effective therapeutic option for patients with ROS1-, NTRK1-3-,
      or ALK-rearranged malignancies who have progressed on earlier-generation TKIs.
      Cancer Discov; 8(10); 1227-36. (c)2018 AACR. This article is highlighted in the
      In This Issue feature, p. 1195.

PMID- 30093505
TI  - Ivosidenib Gets Go-Ahead for AML.
AB  - The FDA approved ivosidenib for patients with IDH1-mutant relapsed/refractory
      acute myeloid leukemia. The approval was based on results of a phase I trial in
      which 32.8% of patients treated with the drug had a complete remission or a
      complete remission with a partial hematologic recovery.

PMID- 30093507
TI  - Biomarkers for the diagnosis of venous thromboembolism: D-dimer, thrombin
      generation, procoagulant phospholipid and soluble P-selectin.
AB  - BACKGROUND: The diagnostic algorithm for venous thromboembolism (VTE) currently
      involves a composite of pre-test probability, D-dimer and imaging. Other
      laboratory tests, however, may assist in the identification of patients with VTE.
      AIM: To assess the accuracy of different coagulation tests (D-dimer, thrombin
      generation, phospholipid-dependent (PPL) clotting time, soluble P-selectin (sP
      selectin)) as biomarkers of acute VTE. METHODS: Random samples arriving at the
      Coagulation Laboratory at Mater Dei Hospital (Msida, Malta) from the Accident and
      Emergency Department with a request for D-dimer measurement were collected
      between August 2015 and February 2016. The following tests were performed:
      Innovance D-dimer (Siemens Healthcare Diagnostics), HemosIL D-dimer HS
      (Instrumentation Laboratory), thrombin generation (using the calibrated automated
      thrombogram), STA Procoag PPL (Diagnostica Stago) and sP-selectin (Affymetrix;
      eBioscience). VTE was objectively confirmed by compression ultrasonography, CT
      pulmonary angiography or ventilation/perfusion lung scan. RESULTS: 100 samples
      were collected (33 with VTE). A strong positive linear correlation was found
      between the two D-dimer tests (r=0.97, p<0.001). Patients with VTE showed
      significantly higher sP-selectin concentrations compared with patients without
      VTE (75.7 ng/mL vs 53.0 ng/mL, p<0.001). In the random forest plot, the two D
      dimer assays showed the highest variable importance, followed by sP-selectin. A
      sP-selectin cut-off of 74.8 ng/mL was associated with 72.7% sensitivity and 78.2%
      specificity for acute VTE in our cohort. CONCLUSION: Our results confirmed D
      dimer as the main biomarker of VTE and speculated a role for sP-selectin. The
      impact of thrombin generation was limited and no role emerged for the PPL
      clotting time. These observations need to be confirmed in large management
      studies.

PMID- 30093508
TI  - Many faces of the same myeloid neoplasm: a case of leukaemia cutis with mixed
      histiocytic and Langerhans cell differentiation.

PMID- 30093506
TI  - The BTK Inhibitor ARQ 531 Targets Ibrutinib-Resistant CLL and Richter
      Transformation.
AB  - Targeted inhibition of Bruton tyrosine kinase (BTK) with the irreversible
      inhibitor ibrutinib has improved outcomes for patients with hematologic
      malignancies, including chronic lymphocytic leukemia (CLL). Here, we describe
      preclinical investigations of ARQ 531, a potent, reversible inhibitor of BTK with
      additional activity against Src family kinases and kinases related to ERK
      signaling. We hypothesized that targeting additional kinases would improve global
      inhibition of signaling pathways, producing more robust responses. In vitro
      treatment of patient CLL cells with ARQ 531 decreases BTK-mediated functions
      including B-cell receptor (BCR) signaling, viability, migration, CD40 and CD86
      expression, and NF-kappaB gene transcription. In vivo, ARQ 531 was found to
      increase survival over ibrutinib in a murine EMU-TCL1 engraftment model of CLL
      and a murine EMU-MYC/TCL1 engraftment model resembling Richter transformation.
      Additionally, ARQ 531 inhibits CLL cell survival and suppresses BCR-mediated
      activation of C481S BTK and PLCgamma2 mutants, which facilitate clinical
      resistance to ibrutinib.Significance: This study characterizes a rationally
      designed kinase inhibitor with efficacy in models recapitulating the most common
      mechanisms of acquired resistance to ibrutinib. Reversible BTK inhibition is a
      promising strategy to combat progressive CLL, and multikinase inhibition
      demonstrates superior efficacy to targeted ibrutinib therapy in the setting of
      Richter transformation. Cancer Discov; 8(10); 1300-15. (c)2018 AACR. This article
      is highlighted in the In This Issue feature, p. 1195.

PMID- 30093509
TI  - Community-based health insurance and healthcare service utilisation, North-West,
      Ethiopia: a comparative, cross-sectional study.
AB  - OBJECTIVES: The objective of this study was to compare differences in healthcare
      utilisation between community-based health insurance member households and non
      member households and to identify factors for community-based health insurance
      enrolment in South Achefer District. DESIGN: Comparative, cross-sectional study.
      SETTINGS: Community-based. PARTICIPANTS: A total of 652 selected households (326
      insured and 326 uninsured households) participated in the study. METHODS: A two
      sample t-test (for proportions) and chi2 (for categorical data) were computed.
      MAIN OUTCOME MEASURE: Utilisation of healthcare. RESULTS: There was a significant
      difference in the rate of healthcare utilisation between insured (50.5%) and
      uninsured (29.3%) households (chi2=27.864, p<0.001). Significant variations of
      enrolment status in community-based health insurance were observed in the
      following variables: educational status, family size, occupation, marital status,
      travel time to the nearest health institution, perceived quality of care, first
      choice of place for treatment during illness and expected healthcare cost of a
      recent treatment. CONCLUSIONS: Utilisation of health services among insured
      households with community-based health insurance was higher. Educational status,
      family size, occupation, marital status, travel time to the nearest health
      institution, perceived quality of care, first choice of place for treatment
      during illness and expected healthcare cost of a recent treatment should be
      emphasised to enhance community health insurance enrolment.

PMID- 30093511
TI  - Evaluation of ADA HbA1c criteria in the diagnosis of pre-diabetes and diabetes in
      a population of Chinese adolescents and young adults at high risk for diabetes: a
      cross-sectional study.
AB  - OBJECTIVE: We aimed to assess haemoglobin A1c (HbA1c) for the diagnosis of pre
      diabetes and diabetes in a population of Chinese youths at risk of metabolic
      syndrome. SETTING: Beijing, China. PARTICIPANTS: A total of 581 subjects aged 14
      28 years underwent evaluation including an oral glucose tolerance test (OGTT).
      Insulin sensitivity, beta-cell function and a number of cardiovascular disease
      risk factors were evaluated. Receiver operating characteristic (ROC) curves were
      used to assess the screening efficacy of HbA1c. RESULTS: Using OGTT data as a
      standard, the majority (70.0%, 7/10) of subjects with diabetes would have been
      diagnosed with HbA1c >=6.5%. In contrast, only 28.1% (16/57) of subjects with pre
      diabetes possessed elevated HbA1cs, while the majority (68.4%) had normal HbA1cs.
      On the contrary, a total of 8.1% (39/479) of youths in the normal HbA1c category
      (<5.7%) and 21.3% in the pre-diabetes category had pre-diabetes. In the ROC
      analysis, the area under the curve (AUC) for HbA1c identifying pre-diabetes was
      0.680(95% CI 0.640 to 0.719); the optimal threshold was 5.5%, with a sensitivity
      of 61.4% and specificity of 68.5%. For type 2 diabetes mellitus, the AUC for
      HbA1c was 0.970 (0.952 to 0.982), and the optimal threshold was 6.1%, with a
      sensitivity of 90.0% and a specificity of 98.7%. Applying these new cut-offs, pre
      diabetic participants (HbA1c 5.5%-6.1%) had lower disposition index and higher
      risk of dyslipidaemia (OR=1.61,95% CI 1.10 to 2.37) and metabolic syndrome
      (OR=2.09, 1.27 to 3.45) than those with normal HbA1c (<5.5%). CONCLUSION: The
      American Diabetes Association's established HbA1c criteria for pre-diabetes and
      diabetes (5.7% and 6.5%) may not be appropriately applied to adolescents and
      young adults in China. Our findings suggest that those with HbA1c of 5.5%-6.1%
      already exhibit impaired beta-cell function and increased cardiometabolic risk
      factors which may warrant intervention. TRIAL REGISTRATION NUMBER: NCT03421444.

PMID- 30093510
TI  - Robot-assisted radical cystectomy with intracorporeal urinary diversion versus
      open radical cystectomy (iROC): protocol for a randomised controlled trial with
      internal feasibility study.
AB  - INTRODUCTION: Bladder cancer (BC) is a common malignancy and one of the most
      expensive to manage. Radical cystectomy (RC) with pelvic lymphadenectomy is a
      gold standard treatment for high-risk BC. Reductions in morbidity and mortality
      from RC may be achieved through robot-assisted RC (RARC). Prospective comparisons
      between open RC (ORC) and RARC have been limited by sample size, use of
      extracorporeal reconstruction and use of outcomes important for ORC. Conversely,
      while RARC is gaining in popularity, there is little evidence to suggest it is
      superior to ORC. We are undertaking a prospective randomised controlled trial
      (RCT) to compare RARC with intracorporeal reconstruction (iRARC) and ORC using
      multimodal outcomes to explore qualitative and quantitative recovery after
      surgery. METHODS AND ANALYSIS: iROC is a multicentre prospective RCT in English
      National Health Service (NHS) cancer centres. We will randomise 320 patients
      undergoing RC to either iRARC or ORC. Treatment allocation will occur after trial
      entry and consent. The primary outcome is days alive and out of hospital within
      the first 90 days from surgery. Secondary outcomes will measure functional
      recovery (activity trackers, chair-to-stand tests and health related quality of
      life (HRQOL) questionnaires), morbidity (complications and readmissions), cost
      effectiveness (using EuroQol-5 Domain-5 levels (EQ-5D-5L) and unit costs) and
      surgeon fatigue. Patients will be analysed according to intention to treat. The
      primary outcome will be transformed and analysed using regression. All
      statistical assumptions will be investigated. Secondary outcomes will be analysed
      using appropriate regression methods. An internal feasibility study of the first
      30 patients will evaluate recruitment rates, acceptance of randomised treatment
      choice, compliance outcome collection and to revise our sample size. ETHICS AND
      DISSEMINATION: The study has ethical approval (REC reference 16/NE/0418).
      Findings will be made available to patients, clinicians, funders and the NHS
      through peer-reviewed publications, social media and patient support groups.
      TRIAL REGISTRATION NUMBERS: ISRCTN13680280 and NCT03049410.

PMID- 30093514
TI  - Development of a simple, practice-based tool to assess quality of paediatric
      emergency care delivery in resource-limited settings: identifying critical
      actions via a Delphi study.
AB  - OBJECTIVE: Provision of timely, high-quality care for the initial management of
      critically ill children in African hospitals remains a challenge. Monitoring the
      completion of critical actions during resuscitations can inform efforts to reduce
      variability and improve outcomes. We sought to develop a practice-based tool
      based on contextually relevant actions identified via a Delphi process. Our goal
      was to develop a tool that could identify gaps in care, facilitate identification
      of training and standardised assessment to support quality improvement efforts.
      DESIGN: Six sentinel conditions were selected based on disease epidemiology and
      mortality at rural and urban African emergency departments. Potential critical
      actions were identified through focused literature review. These actions were
      evaluated within a three-round modified Delphi process. A set of logistical
      filters was applied to the candidate list to derive a practice-based tool.
      SETTING AND PARTICIPANTS: Attendees at an international emergency medicine
      conference comprised an expert panel of 25 participants, with 84% working
      primarily in African settings. Consensus rounds allowing novel responses were
      conducted via online and in-person surveys. RESULTS: The expert panel generated
      199 actions that apply to six conditions in emergently ill children. Application
      of appropriateness criteria refined this to 92 candidate actions across the
      following seven categories: core skills, active seizure, altered mental status,
      diarrhoeal illness, febrile illness, respiratory distress and polytrauma. From
      these, we identified 28 actions for inclusion in a practice-based tool
      contextually relevant to the initial management of critically ill children in
      Africa. CONCLUSIONS: A group consensus process identified critical actions for
      severely ill children with select sentinel conditions in emergency paediatric
      care in an African setting. Absence of these actions during resuscitation might
      reflect modifiable gaps in quality of care. The resulting practice-based tool is
      context relevant and can serve as a foundation for training and quality
      improvement efforts in African hospitals and emergency departments.

PMID- 30093513
TI  - Sexual minority status and suicidal behaviour among Chinese adolescents: a
      nationally representative cross-sectional study.
AB  - OBJECTIVES: Suicidality among sexual minority adolescents has generated worldwide
      concern in recent decades, and previous Western studies have demonstrated that
      sexual minority status is associated with adolescent suicidality. However,
      whether this association exists in Chinese adolescents remains largely unknown.
      This study aimed to estimate the associations between sexual minority status and
      suicidal behaviour among Chinese adolescents. DESIGN: Cross-sectional survey.
      SETTING: A total of 506 high schools in 7 provinces of China. PARTICIPANTS: A
      total of 150 822 students in grades 7-12 who completed the questionnaires
      (response rate of 95.9%) were included. MAIN OUTCOME MEASURES: Suicidal ideation
      and suicide attempts were used to measure suicidal behaviour, and sexual
      attraction (opposite sex, same sex or both sex) was used as a measure for sexual
      minority status. RESULTS: Of the 150 822 adolescents analysed, 4.1% self-reported
      as sexual minorities and 17.3% were unsure. Compared with heterosexual and unsure
      adolescents, same-sex romantic attraction (SSA) and both-sex romantic attraction
      (BSA) adolescents reported a higher prevalence of past-year suicidal ideation
      (SSA: 21.6% for males and 30.4% for females; BSA: 34.7% for males and 42.3% for
      females) and suicide attempts (SSA: 6.9% for males and 8.9% for females; BSA:
      12.2% for males and 10.9% for females). After adjustment for covariates, SSA and
      BSA adolescents were more likely to have past-year suicidal ideation and suicide
      attempts than their heterosexual and unsure peers. BSA adolescents reported the
      highest risk of suicidal ideation (males: adjusted OR (AOR) 2.42, 95% CI 2.03 to
      2.88; females: AOR 2.61, 95% CI 2.41 to 2.82) and suicide attempts (males: AOR
      3.83, 95% CI 2.85 to 5.14; females: AOR 2.59, 95% CI 2.19 to 3.06). CONCLUSIONS:
      Our study suggested that Chinese sexual minority adolescents were at increased
      risk of suicidality, and those with BSA had an especially high risk in this
      population. These findings emphasised the urgent need to develop targeted
      interventions to effectively address suicide-related problems among Chinese
      sexual minority adolescents.

PMID- 30093512
TI  - Does the performance of five back-associated exercises relate to the presence of
      low back pain? A cross-sectional observational investigation in regional
      Australian council workers.
AB  - OBJECTIVES: Investigate the relationships between the ability/inability to
      perform five physical test exercises and the presence or absence of low back pain
      (LBP). SETTING: Regional Australian council training facility. PARTICIPANTS:
      Consecutive participants recruited during 39 back education classes (8-26
      participants per class) for workers in general office/administration,
      parks/gardens maintenance, roads maintenance, library, child care and management.
      Total sample (n=539) was reduced through non-consent and insufficient demographic
      data to n=422. Age 38.6+/-15.3 years, range 18-64 years, 67.1% male. METHODS:
      Cross-sectional, exploratory, observational investigation. LBP presence was
      ascertained from a three-response option questionnaire: 0=none/rarely (no)
      1=sometimes (some), 2=mostly/always (most). Statistical correlation was performed
      with the number of the five test exercises the individual successfully performed:
      (1) extension in lying: 3 s; (2) 'toilet squat'; feet flat, feet touched: 3 s;
      (3) full squat then stand up: 5 times; (4) supine sit-up, knees flexed: 10 times;
      and (5) leg extension, supine bilateral: 10 times. INTERVENTIONS: Nil. RESULTS:
      For the group 'no-some', 94.3% completed 4-5 test exercises, while for group
      'With', 95.7% completed 0-1 test exercises. The relationship between LBP presence
      and number of exercises performed was highly significant (chi2(10)=300.61,
      p<0.001). Furthermore, multinomial logistic regression predicting LBP (0=no,
      1=some, 2=most) from the number of exercises completed, substantially improved
      the model fit (initial-2LL=348.246, final-2LL=73.620, chi2(2)=274.626, p<0.001).
      As the number of exercises performed increased, the odds of reporting 'some LBP'
      or 'most LBP' dropped substantially (ORs of 0.34 and 0.17, respectively).
      CONCLUSION: The ability to complete/not complete five test exercises correlated
      statistically and significantly with a higher LBP absence/presence in a general
      working population. Training individuals to complete such exercises could
      facilitate reductions in LBP incidence; however, causality cannot be inferred.
      Randomised trials are recommended to establish the potential efficacy of exercise
      based approaches, considering these five selected exercises, for predicting and
      managing LBP.

PMID- 30093516
TI  - Mixed methods process evaluation of an enhanced community-based rehabilitation
      intervention for elderly patients with hip fracture.
AB  - OBJECTIVES: To describe the implementation of an enhanced rehabilitation
      programme for elderly hip fracture patients with mental capacity, in a randomised
      feasibility study compared with usual rehabilitation. To compare processes
      between the two and to collect the views of patients, carers and therapy staff
      about trial participation. DESIGN: Mixed methods process evaluation in a
      randomised feasibility study. SETTING: Patient participants were recruited on
      orthopaedic and rehabilitation wards; the intervention was delivered in the
      community following hospital discharge. PARTICIPANTS: Sixty-one older adults
      (aged >=65 years) recovering from surgical treatment (replacement arthroplasty or
      internal fixation) following hip fracture, who were living independently prior to
      fracture and had mental capacity and 31 of their carers. INTERVENTIONS: Usual
      care (control) or usual care plus an enhanced rehabilitation package
      (intervention). The enhanced rehabilitation consisted of a patient-held
      information workbook, goal-setting diary and up to six additional therapy
      sessions. PROCESS EVALUATION COMPONENTS: Recruitment of sites and rehabilitation
      teams, response of rehabilitation teams, recruitment and reach in patient and
      carer participants, intervention delivery, delivery to individuals, response of
      individual patients to the enhanced intervention or usual rehabilitation,
      response of carer participants, unintended consequences and testing intervention
      theory and context. RESULTS: Usual rehabilitation care was very variable. The
      enhanced rehabilitation group received a mean of five additional therapy
      sessions. All of the returned goal-setting diaries had inputs from the therapy
      team, and half had written comments by the patients and carers. Focus group
      themes: variation of usual care and its impact on delivering the intervention;
      the importance of goal setting; the role of the therapist in providing
      reassurance about safe physical activities; and acceptability of the extra
      therapy sessions. CONCLUSIONS: Lessons learnt for a future definitive RCT include
      how to enhance recruitment and improve training materials, the workbook, delivery
      of the extra therapy sessions and recording of usual rehabilitation care. TRIAL
      REGISTRATION NUMBER: ISRCTN22464643; Post- results.

PMID- 30093515
TI  - Sociodemographic and psychological determinants of influenza vaccine intention
      among recipients of autologous and allogeneic haematopoietic stem cell
      transplant: a cross-sectional survey of UK transplant recipients using a modified
      health belief model.
AB  - OBJECTIVES: Studies exploring vaccination rates among haematopoietic stem cell
      transplant (HSCT) recipients have focused on physician factors that limit uptake.
      Understanding the patient factors that determine vaccination intention is crucial
      to delivering a successful vaccination programme. Using a modified health belief
      model (mHBM), we conducted a cross-sectional survey with the objective of
      exploring the sociodemographic and psychological factors that determined
      autologous and allogeneic HSCT recipients' intention to receive the seasonal
      inactivated influenza vaccine (SIIV) during the 2015-2016 influenza season.
      SETTING: The setting of our study was three tertiary level, UK National Health
      Service (NHS) autologous and allogeneic HSCT centres. PARTICIPANTS: Eligible
      patients were aged 16 years or over and recipients of autologous or allogeneic
      HSCT for any disease indication, with no absolute contraindication to receiving
      the SIIV during the next influenza season, and having not received the SIIV since
      transplant. 93 participants from 3 UK NHS HSCT centres completed an anonymous
      study-specific questionnaire. 78.5% were recipients of allogeneic and 21.5%
      autologous HSCT. RESULTS: 23.7% of participants expressed low intent to receive
      the SIIV. Patients aged over 65 (OR 0.02, 95% CI 0.01 to 0.57, p=0.02) and those
      who had not received the SIIV prior to HSCT (OR 0.04, 95% CI 0.02 to 0.56,
      p=0.02) were less likely to have high intent. A multivariate logistic regression
      model incorporating constructs of the mHBM was statistically significant
      (p<0.001) and explained 74.7% of variation in SIIV intention. More patients felt
      that a recommendation from their HSCT team than their general practitioner would
      prompt them to receive the SIIV, and this was most pronounced in those who had
      low intent. CONCLUSIONS: The mHBM may provide a useful structure for addressing
      low vaccine intent among HSCT recipients and further interventional studies are
      warranted. We would encourage HSCT and general practitioners to discuss SIIV
      intention as a routine part of care.

PMID- 30093517
TI  - Determinants of patient choice for hospital readmission after township
      hospitalisation: a population-based retrospective study in China.
AB  - OBJECTIVE: The lack of coordinated and appropriate healthcare across sectors has
      produced more patients for county hospitals in China. This study examined
      differences in patient choice between township and county hospitals for
      readmission after a first township hospitalisation, and the determinants that
      influenced this choice. DESIGN: A retrospective study of readmissions across
      hospitals after a first admission in township hospital. A township-township (TT)
      inpatient group and a township-county (TC) inpatient group were compared. A two
      level logistic regression model was used to examine the determinants of choice
      for hospital readmission. SETTING: Data were drawn from a population-based health
      utilisation database for Qianjiang District, China, from 1 January 2008 to 31
      December 2013. PARTICIPANTS: This study focused on readmitted patients whose
      first admission was in a township hospital. Readmission cases were identified as
      the same diagnosis (International Classification of Diseases, Tenth Revision) in
      a subsequent hospitalisation within 30 days. In total, 6764 readmissions had
      first admissions in township hospitals. PRIMARY OUTCOME MEASURES: Patient choice
      for hospital readmission after a first township hospitalisation. RESULTS: The TT
      group accounted for 62.5% (4225) and the TC group for 37.5% (2539) of
      readmissions in 6 years, and the proportion of TC readmissions in total
      inpatients increased from 1.66% to 1.89%. Readmission rates varied among towns
      (p<0.001). Differences between the TC and TT groups included: length of stay
      (LOS) of first admission (6.96 days vs 9.23 days), average interval between
      admissions (6.03 days vs 14.95 days) and disease category. Admission year, age,
      travel time to county hospital, interval between admissions, first admission LOS
      and disease category were determinants of choice for hospital readmission.
      CONCLUSIONS: Patients whose first admission was in a township hospital were more
      likely to be readmitted to a county hospital. A combination of first LOS and
      interval between admissions may be an effective identification index for TC
      readmission. TRIAL REGISTRATION NUMBER: ChiCTR-OOR-14005563.

PMID- 30093519
TI  - Arthroscopic-assisted balloon tibioplasty versus open reduction internal fixation
      (ORIF) for treatment of Schatzker II-IV tibial plateau fractures: study protocol
      of a randomised controlled trial.
AB  - INTRODUCTION: Arthroscopic-assisted balloon tibioplasty is an emerging technology
      that has shown advantages in recovering depression of the articular surface.
      However, studies evaluating clinical outcomes between arthroscopic-assisted
      balloon tibioplasty and traditional open reduction internal fixation (ORIF) are
      sparse. This is the first randomised study to compare arthroscopic-assisted
      balloon tibioplasty with ORIF, and will provide guidance for treating patients
      with Schatzker types II, III and IV with depression of the medial tibial plateau
      only. METHODS AND ANALYSIS: A blinded randomised controlled trial will be
      conducted and a total of 80 participants will be randomly divided into either the
      arthroscopic-assisted balloon tibioplasty group or the ORIF group, at a ratio of
      1:1. The primary clinical outcome measures are the knee functional scores,
      Rasmussen radiological evaluation scores and the quality of reduction based on
      postoperative CT scan. Secondary clinical outcome measures are intraoperative
      blood loss, surgical duration, visual analogue scale score after surgery,
      hospital duration after surgery, complications and 36-Item Short-Form Health
      Survey score. ETHICS AND DISSEMINATION: This study has been reviewed and approved
      by the Institutional Review Board of the Second Affiliated Hospital of Wenzhou
      Medical University (batch: 2017-12). The results will be presented in peer
      reviewed journals after completion of the study. TRIAL REGISTRATION NUMBER:
      NCT03327337, Pre-results.

PMID- 30093518
TI  - Maternal anemia and underweight as determinants of pregnancy outcomes: cohort
      study in eastern rural Maharashtra, India.
AB  - OBJECTIVES: To study the trend in the prevalence of anaemia and low BMI among
      pregnant women from Eastern Maharashtra and evaluate if low BMI and anaemia
      affect pregnancy outcomes. DESIGN: Prospective observational cohort study.
      SETTING: Catchment areas of 20 rural primary health centres in four eastern
      districts of Maharashtra State, India. PARTICIPANTS: 72 750 women from the Nagpur
      site of Maternal and Newborn Health Registry of NIH's Global Network, enrolled
      from 2009 to 2016. MAIN OUTCOME MEASURES: Mode of delivery, pregnancy related
      complications at delivery, stillbirths, neonatal deaths and low birth weight
      (LBW) in babies. RESULTS: Over 90% of the women included in the study were
      anaemic and over a third were underweight (BMI <18 kg/m2) and with both
      conditions. Mild anaemia at any time during delivery significantly increased the
      risk (Risk ratio; 95% confidence interval (RR;(95% CI)) of stillbirth (1.3 (1.1
      1.6)), neonatal deaths (1.3 (1-1.6)) and LBW babies (1.1 (1-1.2)). The risks
      became even more significant and increased further with moderate/severe anaemia
      any time during pregnancy for stillbirth (1.4 (1.2-1.8)), neonatal deaths (1.7
      (1.3-2.1)) and LBW babies (1.3 (1.2-1.4)).,. Underweight at anytime during
      pregnancy increased the risk of neonatal deaths (1.1 (1-1.3)) and LBW babies
      (1.2;(1.2-1.3)).The risk of having stillbirths (1.5;(1.2-1.8)), neonatal deaths
      (1.7;(1.3-2.3)) and LBW babies (1.5;(1.4-1.6)) was highest when - the anaemia and
      underweight co-existed in the included women. Obesity/overweight during pregnancy
      increased the risk of maternal complications at delivery (1.6;(1.5-1.7)) and of
      caesarean section (1.5;(1.4-1.6)) and reduced the risk of LBW babies 0.8 (0.8
      0.9)). CONCLUSION: Maternal anaemia is associated with enhanced risk of
      stillbirth, neonatal deaths and LBW. The risks increased if anaemia and
      underweight were present simultaneously. TRIAL REGISTRATION NUMBER: NCT01073475.

PMID- 30093521
TI  - Ethnic differences in frailty: a cross-sectional study of pooled data from
      community-dwelling older persons in the Netherlands.
AB  - OBJECTIVE: Few European studies examined frailty among older persons from diverse
      ethnic backgrounds. We aimed to examine the association of ethnic background with
      frailty. In addition, we explored the association of ethnic background with
      distinct components that are considered to be relevant for frailty. DESIGN AND
      SETTING: This was a cross-sectional study of pooled data of The Older Persons and
      Informal Caregivers Survey Minimum DataSet (TOPICS) in the Netherlands.
      PARTICIPANTS: Community-dwelling persons aged 55 years and older with a Dutch,
      Indonesian, Surinamese, Moroccan or Turkish ethnic background were included (n=23
      371). MEASUREMENTS: Frailty was assessed with the validated TOPICS-Frailty Index
      that consisted of 45 items. The TOPICS-Frailty Index contained six components:
      morbidities, limitations in activities of daily living (ADL), limitations in
      instrumental ADL, health-related quality of life, psychosocial health and self
      rated health. To examine the associations of ethnic background with frailty and
      with distinct frailty components, we estimated multilevel random-intercept models
      adjusted for confounders. RESULTS: TOPICS-Frailty Index scores varied from 0.19
      (SD=0.12) among persons with a Dutch background to 0.29 (SD=0.15) in persons with
      a Turkish background. After adjustment for age, sex, living arrangement and
      education level, persons with a Turkish, Moroccan or Surinamese background were
      frailer compared with persons with a Dutch background (p<0.001). There were no
      significant differences in frailty between persons with an Indonesian compared
      with a Dutch background. The IADL component scores were higher among all groups
      with a non-Dutch background compared with persons with a Dutch background (p<0.05
      or lower for all groups). CONCLUSIONS: Compared with older persons with a Dutch
      background, persons with a Surinamese, Moroccan or Turkish ethnic background were
      frailer. Targeted intervention strategies should be developed for the prevention
      and reduction of frailty among these older immigrants.

PMID- 30093520
TI  - Psychometric properties of the Patient Reported Outcomes, Burdens and Experiences
      (PROBE) questionnaire.
AB  - OBJECTIVE: To assess the psychometric properties of the Patient Reported
      Outcomes, Burdens and Experiences (PROBE) questionnaire. METHODS: This study was
      a cross-sectional, multinational study. Participants were enrolled if they were
      more than 10 years old and people with haemophilia A or B or people without a
      bleeding disorder. Participants were invited through non-governmental patient
      organisations in 21 countries between 01/27/2016 and 02/23/2017. The following
      psychometric properties: missing data, floor and ceiling effects, exploratory
      factor analysis and internal consistency reliability were examined. A PROBE Score
      was derived and assessed for its convergent and known groups validity. RESULTS:
      The study analysed the data on 916 participants with median age of 37.0 (IQR 27.0
      to 48.0) years, 74.8% male. In the domain assessing patient-reported outcomes
      (PROs), more than 15% of participants presented a ceiling effect for all items
      but two, and a floor effect for one item. Factor analysis identified three
      factors explaining the majority of the variance. Cronbach's alpha coefficient
      indicated good internal consistency reliability (0.84). PROBE items showed
      moderate to strong correlations with corresponding EuroQol five dimension 5-level
      instrument (EQ-5D-5L) domains. The PROBE Score has a strong correlation (r=0.67)
      with EQ-5D-5L utility index score. The PROBE Score has a known groups validity
      among various groups. CONCLUSIONS: The results of this study suggest that PROBE
      is a valid questionnaire for evaluating PROs in people with haemophilia as well
      as control population. The known-group property of PROBE will allow its use in
      future clinical trials, longitudinal studies, health technology assessment
      studies, routine clinical care or registries. Additional studies are needed to
      test responsiveness and sensitivity to change. TRIAL REGISTRATION NUMBER:
      NCT02439710; Results.

PMID- 30093522
TI  - Integration of musculoskeletal physical therapy care in the patient-centred
      medical home (IMPaC): protocol for a single-site randomised clinical trial.
AB  - INTRODUCTION: Annually, >50% of the US population reports musculoskeletal (MSK)
      pain to a provider, with direct healthcare costs exceeding $185 billion. The
      number of MSK complaints and the associated costs are projected to rise,
      increasing demand for and burden on providers. Establishing new care models to
      decrease inefficiencies may lower costs and optimise care delivery. The purpose
      of the Integration of Musculoskeletal Physical Therapy Care in the Patient
      Centred Medical Home (IMPaC) study is to compare initial evaluation by a physical
      therapist (PT) integrated into primary care versus initial evaluation by a
      primary care provider (PCP) for patients with an MSK complaint. METHODS AND
      ANALYSIS: This single-site, randomised clinical trial will test the hypothesis
      that a PT within a primary care facility as the initial evaluating provider for
      patients with an MSK complaint will lower costs, improve utilisation (ie, reduced
      opioid prescriptions, imaging, physical therapy, emergency department visits and
      missed appointments) and increase patient satisfaction within 90 days of the
      index visit compared with PCP evaluation in the same location. Participants aged
      >=18 years will be randomised with equal allocation and stratified by pain site
      (ie, back, knee, upper extremity and other). In the initial PT evaluation arm,
      patients will be assessed, treated and then instructed to complete a home
      exercise programme. The PCP cohort will undergo a usual PCP evaluation, and if a
      referral to physical therapy is made, patients will be randomised to onsite
      versus offsite physical therapy. Differences will be calculated and tested across
      the two arms. ETHICS AND DISSEMINATION: Approval was received from the Duke
      University Institutional Review Board (01 May 2017) and the National Institutes
      of Health, National Centre for Advancing Translational Sciences (01 January
      2017). Findings will be communicated via quarterly reports to funding bodies and
      disseminated through scientific publications. TRIAL REGISTRATION NUMBER:
      NCT03110211; Pre-results.

PMID- 30093523
TI  - Protocol for the avatar acceptability study: a multiperspective cross-sectional
      study evaluating the acceptability of using patient-derived xenografts to guide
      personalised cancer care in Australia and New Zealand.
AB  - INTRODUCTION: Patient-derived xenografts (PDXs) have the potential to transform
      personalised cancer care, however, little is known about the acceptability of
      using PDXs to guide treatment decision-making. Given that patient and community
      preferences can influence satisfaction with care as well as the success of new
      technologies, we will evaluate the acceptability of PDXs in individuals affected
      by cancer and community comparisons. METHODS AND ANALYSIS: This comparative cross
      sectional study will recruit 323 individuals affected by cancer (cancer survivors
      (of childhood or adult cancer) and parents of childhood cancer survivors) and 323
      community comparisons (adults and parents). We will collect data via structured
      interviews and questionnaires. To determine the acceptability of PDXs, we will
      assess five domains: willingness to use PDXs when/if diagnosed with cancer,
      perceived advantages and disadvantages of PDXs, maximum acceptable out-of-pocket
      costs per patient, maximum acceptable turnaround time to receive results and
      maximum acceptable number of mice sacrificed per patient. The primary endpoint
      will be participants' decisional balance ratio (calculated as participants'
      advantages ratings divided by perceived disadvantages ratings). ETHICS AND
      DISSEMINATION: The study protocol has been approved by the South Eastern Sydney
      Local Health District Human Research Ethics Committee (HREC:12/173) and UNSW
      Sydney (HC15773). The results will be disseminated in peer-reviewed journals and
      at scientific conferences. A lay summary will be published on the Behavioural
      Sciences Unit website.

PMID- 30093525
TI  - Beyond the Safe Motherhood Initiative: Accelerated Action Urgently Needed to End
      Preventable Maternal Mortality.

PMID- 30093528
TI  - Retrotransposon Insertion and DNA Methylation Regulate Aluminum Tolerance in
      European Barley Accessions.
AB  - Aluminum (Al) toxicity is a major stress factor limiting crop productivity in
      acid soil. Although there is great genotypic variation in tolerance to Al
      toxicity, the underlying molecular mechanisms are poorly understood. Here, we
      report that, in barley (Hordeum vulgare), the fourth largest cereal crop produced
      in the world, both retrotransposon insertion and DNA methylation are involved in
      regulating differential Al tolerance. HvAACT1 is a major gene responsible for
      citrate secretion from the roots for external detoxification of Al. A
      multiretrotransposon-like (MRL) sequence insertion at least 15.3 kb in length was
      detected in the upstream genomic region of HvAACT1 that displayed promoter
      activity and significantly enhanced HvAACT1 expression, especially in the root
      tips of Al-tolerant accessions. Furthermore, in a number of accessions with low
      levels of HvAACT1 expression, this MRL insertion was present but highly
      methylated. Geographical analysis showed that accessions with this MRL insertion
      are distributed mainly in European areas with acid soils. Two wild barley
      accessions were found to possess this MRL insertion, but with a high degree of
      methylation. These results indicate that the MRL insertion and its degree of DNA
      methylation influence HvAACT1 expression and that demethylation of this MRL
      insertion, which facilitates adaptation to acid soils, occurred following barley
      domestication. Moreover, our results indicate that barley accessions in East Asia
      and Europe have developed independent but equivalent strategies to withstand Al
      toxicity in acid soils.

PMID- 30093524
TI  - Carboxamido steroids inhibit the opening properties of transient receptor
      potential ion channels by lipid raft modulation.
AB  - Transient Receptor Potential (TRP) cation channels, like the TRP Vanilloid 1
      (TRPV1) and TRP Ankyrin 1 (TRPA1), are expressed on primary sensory neurons.
      These thermosensor channels play a role in pain processing. We have provided
      evidence previously that lipid raft disruption influenced the TRP channel
      activation, and a carboxamido-steroid compound (C1) inhibited TRPV1 activation.
      Therefore, our aim was to investigate whether this compound exerts its effect
      through lipid raft disruption and the steroid backbone (C3) or whether altered
      position of the carboxamido group (C2) influences the inhibitory action by
      measuring Ca2+ transients on isolated neurons and calcium-uptake on receptor
      expressing CHO cells. Membrane cholesterol content was measured by filipin
      staining and membrane polarization by fluorescence spectroscopy. Both the
      percentage of responsive cells and the magnitude of the intracellular Ca2+
      enhancement evoked by the TRPV1 agonist capsaicin were significantly inhibited
      after C1 and C2 incubation, but not after C3 administration. C1 was able to
      reduce other TRP channel activation as well. The compounds induced cholesterol
      depletion in CHO cells, but only C1 induced changes in membrane polarization. The
      inhibitory action of the compounds on TRP channel activation develops by lipid
      raft disruption, and the presence and the position of the carboxamido group is
      essential.

PMID- 30093526
TI  - SMALL AUXIN UP RNA62/75 Are Required for the Translation of Transcripts Essential
      for Pollen Tube Growth.
AB  - Successful pollen tube elongation is critical for double fertilization, but the
      biological functions of pollen tube genes and the regulatory machinery underlying
      this crucial process are largely unknown. A previous translatomic study revealed
      two Arabidopsis (Arabidopsis thaliana) SAUR (SMALL AUXIN UP RNA) genes, SAUR62
      and SAUR75, whose expression is up-regulated by pollination. Here, we found that
      both SAUR62 and SAUR75 localized mainly to pollen tube nuclei. The siliques of
      homozygous saur62 (saur62/-), saur75 (saur75/-), and the SAUR62/75 RNA
      interference (RNAi) knockdown line had many aborted seeds. These lines had normal
      pollen viability but defective in vitro and in vivo pollen tube growth, with
      branching phenotypes. Immunoprecipitation with transgenic SAUR62/75-GFP flowers
      revealed ribosomal protein RPL12 family members as potential interacting
      partners, and their individual interactions were confirmed further by yeast two
      hybrid and bimolecular fluorescence complementation assays. Polysome profiling
      showed reduced 80S ribosome abundance in homozygous saur62, saur75, ribosomal
      large subunit12c, and SAUR62/75 RNAi flowers, suggesting that SAUR62/75 play
      roles in ribosome assembly. To clarify their roles in translation, we analyzed
      total proteins from RNAi versus wild-type flowers by isobaric tags for relative
      and absolute quantitation, revealing significantly reduced expression of factors
      participating in pollen tube wall biogenesis and F-actin dynamics, which are
      critical for the elastic properties of tube elongation. Indeed, RNAi pollen tubes
      showed mislocalization of deesterified and esterified pectins and F-actin
      organization. Thus, the biological roles of SAUR62/75 and their RPL12 partners
      are critical in ribosomal pre-60S subunit assembly for efficient pollen tube
      elongation and subsequent fertilization.

PMID- 30093527
TI  - Components of Water Use Efficiency Have Unique Genetic Signatures in the Model C4
      Grass Setaria.
AB  - Plant growth and water use are interrelated processes influenced by genetically
      controlled morphological and biochemical characteristics. Improving plant water
      use efficiency (WUE) to sustain growth in different environments is an important
      breeding objective that can improve crop yields and enhance agricultural
      sustainability. However, genetic improvement of WUE using traditional methods has
      proven difficult due to the low throughput and environmental heterogeneity of
      field settings. To overcome these limitations, this study utilizes a high
      throughput phenotyping platform to quantify plant size and water use of an
      interspecific Setaria italica * Setaria viridis recombinant inbred line
      population at daily intervals in both well-watered and water-limited conditions.
      Our findings indicate that measurements of plant size and water use are
      correlated strongly in this system; therefore, a linear modeling approach was
      used to partition this relationship into predicted values of plant size given
      water use and deviations from this relationship at the genotype level. The
      resulting traits describing plant size, water use, and WUE all were heritable and
      responsive to soil water availability, allowing for a genetic dissection of the
      components of plant WUE under different watering treatments. Linkage mapping
      identified major loci underlying two different pleiotropic components of WUE.
      This study indicates that alleles controlling WUE derived from both wild and
      domesticated accessions can be utilized to predictably modulate trait values
      given a specified precipitation regime in the model C4 genus Setaria.

PMID- 30093529
TI  - Characterization of Tfrc-mutant mice with microcytic phenotypes.
AB  - To identify novel regulators of erythropoiesis, we performed independent forward
      genetic screens using the chemical mutagen ENU in mice. Among progeny displaying
      microcytic red-cell phenotypes, 7 independent mouse strains harboring mutations
      within the transferrin receptor gene Tfrc were identified. Six of the mutants,
      including the previously described red blood cell 6 (RBC6) strain, displayed
      reduced erythroblast CD71 expression and midgestation lethality of homozygotes
      (E12.5-E14.5), and 1 novel strain, RBC21, displayed a variable phenotype with
      sustained CD71 expression and late homozygous lethality (E18.5). Standard iron
      studies were normal in the RBC21 mutant, but intracellular ferritin was
      significantly reduced. The microcytic phenotype seen in the RBC21 strain was the
      result of impaired binding of transferrin to the receptor. Neither RBC6 nor RBC21
      responded to iron replacement therapy. These studies describe how point mutations
      of the transferrin receptor can cause a microcytic anemia that does not respond
      to iron therapy and would not be detected by routine iron studies, such as serum
      ferritin.

PMID- 30093530
TI  - Inter-alpha inhibitor proteins maintain neutrophils in a resting state by
      regulating shape and reducing ROS production.
AB  - The plasma levels of inter-alpha inhibitor proteins (IAIPs) are decreased in
      patients with sepsis and the reduced levels correlate with increased mortality.
      In the present study, we examined the effects of IAIPs on human neutrophils to
      better understand the beneficial effects of IAIPs in the treatment of sepsis. We
      demonstrated that IAIPs induced a spherical shape that was smaller in size with a
      smooth cellular surface in a concentration-dependent manner. These changes were
      inhibited by a specific antibody against IAIPs. In contrast, bikunin, light chain
      of IAIP, had no effect on neutrophil morphology. The neutrophils treated with
      IAIPs could easily pass through the artificial microcapillaries and were
      prevented from entrapment inside the capillaries. Coincubation of human blood
      neutrophils with a confluent human vascular endothelial monolayer showed that
      adhesion of neutrophils on endothelial cells was suppressed by treatment with
      IAIPs. IAIPs inhibited the spontaneous release of reactive oxygen species (ROS)
      in a concentration-dependent fashion. ROS inhibition was associated with
      reductions in p47phox phosphorylation on Ser328. These results suggest that IAIP
      induced morphological changes that render neutrophils quiescent, facilitate
      passage through the microvasculature, and reduce adhesion to vascular endothelial
      cells and production of ROS. Thus, IAIP plays a key role in controlling
      neutrophil activation.

PMID- 30093532
TI  - B cell adaptor for PI3-kinase (BCAP) modulates CD8+ effector and memory T cell
      differentiation.
AB  - CD8+ T cells respond to signals via the T cell receptor (TCR), costimulatory
      molecules, and immunoregulatory cytokines by developing into diverse populations
      of effector and memory cells. The relative strength of phosphoinositide 3-kinase
      (PI3K) signaling early in the T cell response can dramatically influence
      downstream effector and memory T cell differentiation. We show that initial PI3K
      signaling during T cell activation results in up-regulation of the signaling
      scaffold B cell adaptor for PI3K (BCAP), which further potentiates PI3K signaling
      and promotes the accumulation of CD8+ T cells with a terminally differentiated
      effector phenotype. Accordingly, BCAP-deficient CD8+ T cells have attenuated
      clonal expansion and altered effector and memory T cell development following
      infection with Listeria monocytogenes Thus, induction of BCAP serves as a
      positive feedback circuit to enhance PI3K signaling in activated CD8+ T cells,
      thereby acting as a molecular checkpoint regulating effector and memory T cell
      development.

PMID- 30093531
TI  - A phase 1 trial evaluating thioridazine in combination with cytarabine in
      patients with acute myeloid leukemia.
AB  - We completed a phase 1 dose-escalation trial to evaluate the safety of a dopamine
      receptor D2 (DRD2) antagonist thioridazine (TDZ), in combination with cytarabine.
      Thirteen patients 55 years and older with relapsed or refractory acute myeloid
      leukemia (AML) were enrolled. Oral TDZ was administered at 3 dose levels: 25 mg
      (n = 6), 50 mg (n = 4), or 100 mg (n = 3) every 6 hours for 21 days. Intermediate
      dose cytarabine was administered on days 6 to 10. Dose-limiting toxicities (DLTs)
      included grade 3 QTc interval prolongation in 1 patient at 25 mg TDZ and
      neurological events in 2 patients at 100 mg TDZ (gait disturbance, depressed
      consciousness, and dizziness). At the 50-mg TDZ dose, the sum of circulating DRD2
      antagonist levels approached a concentration of 10 MUM, a level noted to be
      selectively active against human AML in vitro. Eleven of 13 patients completed a
      5-day lead-in with TDZ, of which 6 received TDZ with hydroxyurea and 5 received
      TDZ alone. During this period, 8 patients demonstrated a 19% to 55% reduction in
      blast levels, whereas 3 patients displayed progressive disease. The extent of
      blast reduction during this 5-day interval was associated with the expression of
      the putative TDZ target receptor DRD2 on leukemic cells. These preliminary
      results suggest that DRD2 represents a potential therapeutic target for AML
      disease. Future studies are required to corroborate these observations, including
      the use of modified DRD2 antagonists with improved tolerability in AML patients.
      This trial was registered at www.clinicaltrials.gov as #NCT02096289.

PMID- 30093533
TI  - BCAP links IL-1R to the PI3K-mTOR pathway and regulates pathogenic Th17 cell
      differentiation.
AB  - The toll-like receptor (TLR) and interleukin (IL)-1 family of receptors share
      several signaling components, including the most upstream adapter, MyD88. We
      previously reported the discovery of B cell adapter for phosphoinositide 3-kinase
      (BCAP) as a novel toll-IL-1 receptor homology domain-containing adapter that
      regulates inflammatory responses downstream of TLR signaling. Here we find that
      BCAP plays a critical role downstream of both IL-1 and IL-18 receptors to
      regulate T helper (Th) 17 and Th1 cell differentiation, respectively. Absence of
      T cell intrinsic BCAP did not alter development of naturally arising Th1 and Th17
      lineages but led to defects in differentiation to pathogenic Th17 lineage cells.
      Consequently, mice that lack BCAP in T cells had reduced susceptibility to
      experimental autoimmune encephalomyelitis. More importantly, we found that BCAP
      is critical for IL-1R-induced phosphoinositide 3-kinase-Akt-mechanistic target of
      rapamycin (mTOR) activation, and minimal inhibition of mTOR completely abrogated
      IL-1beta-induced differentiation of pathogenic Th17 cells, mimicking BCAP
      deficiency. This study establishes BCAP as a critical link between IL-1R and the
      metabolic status of activated T cells that ultimately regulates the
      differentiation of inflammatory Th17 cells.

PMID- 30093534
TI  - Dissociation of LFP Power and Tuning in the Frontal Cortex during Memory.
AB  - Working memory, the ability to maintain and manipulate information in the brain,
      is critical for cognition. During the memory period of spatial memory tasks,
      neurons in the prefrontal cortex code for memorized locations via persistent,
      spatially tuned increases in activity. Local field potentials (LFPs) are
      understood to reflect summed synaptic activity of local neuron populations and
      may offer a window into network-level processing. We recorded LFPs from areas 8A
      and 9/46 while two male cynomolgus macaques (Macaca fascicularis) performed a
      long duration (5.1-15.6 s) memory-guided saccade task. Greater than ~16 Hz, LFP
      power was contralaterally tuned throughout the memory period. Yet power for both
      contralateral and ipsilateral targets fell gradually after the first second of
      the memory period, dropping below baseline after a few seconds. Our results
      dissociate absolute LFP power from mnemonic tuning and are consistent with
      modeling work that suggests that decreasing synchronization within a network may
      improve the stability of memory coding.SIGNIFICANCE STATEMENT The frontal cortex
      is an important site for working memory. There, individual neurons reflect
      memorized information with selective increases in activity, but how collections
      of neurons work together to achieve memory is not well understood. In this work,
      we examined rhythmic electrical activity surrounding these neurons, which may
      reflect the operation of recurrent circuitry that could underlie memory. This
      rhythmic activity was spatially tuned with respect to memorized locations as long
      as memory was tested (~7.5 s). Surprisingly, however, the overall magnitude of
      rhythmic activity decreased steadily over this period, dropping below baseline
      levels after a few seconds. These findings suggest that collections of neurons
      may actively desynchronize to promote stability in memory circuitry.

PMID- 30093537
TI  - Coherent Activity between the Prelimbic and Auditory Cortex in the Slow-Gamma
      Band Underlies Fear Discrimination.
AB  - The medial prefrontal cortex and the basolateral amygdala (BLA) are essential for
      discriminating between harmful and safe stimuli. The primary auditory cortex
      (Te1) sends projections to both sites, but whether and how it interacts with
      these areas during fear discrimination are poorly understood. Here we show that
      in male rats that can differentiate between a new tone and a threatening one, the
      selective optogenetic inhibition of Te1 axon terminals into the prelimbic (PL)
      cortex shifted discrimination to fear generalization. Meanwhile, no effects were
      detected when Te1 terminals were inhibited in the BLA. Using a combination of
      local field potential and multiunit recordings, we show that in animals that
      discriminate successfully between a new tone and a harmful one, the activity of
      the Te1 and the PL cortex becomes immediately and tightly synchronized in the
      slow-gamma range (40-70 Hz) at the onset of the new tone. This enhanced
      synchronization was not present in other frequency ranges, such as the theta
      range. Critically, the level of gamma synchrony predicted the behavioral choice
      (i.e., no freezing or freezing) of the animals. Moreover, in the same rats, gamma
      synchrony was absent before the fear-learning trial and when animals should
      discriminate between an olfactory stimulus and the auditory harmful one. Thus,
      our findings reveal that the Te1 and the PL cortex dynamically establish a
      functional connection during auditory fear-discrimination processes, and that
      this corticocortical oscillatory mechanism drives the behavioral choice of the
      animals.SIGNIFICANCE STATEMENT Identifying neural networks that infer safety
      versus danger is of great interest in the scientific field. Fear generalization
      reduces the chances of an animal's survival and leads to psychiatric diseases,
      such as post-traumatic stress disorders and phobias in humans. Here we
      demonstrate that animals able to differentiate a new tone from a previous
      threating tone showed synchronization between the prefrontal and primary auditory
      cortices. Critically, this connectivity precedes and predicts the behavioral
      outcome of the animal. Optogenetic inhibition of this functional connectivity
      leads to fear generalization. To the best of our knowledge, this study is the
      first to demonstrate that a corticocortical dialogue occurring between sensory
      and prefrontal areas is a key node for fear-discrimination processes.

PMID- 30093535
TI  - AKAP1 Protects from Cerebral Ischemic Stroke by Inhibiting Drp1-Dependent
      Mitochondrial Fission.
AB  - Mitochondrial fission and fusion impact numerous cellular functions and neurons
      are particularly sensitive to perturbations in mitochondrial dynamics. Here we
      describe that male mice lacking the mitochondrial A-kinase anchoring protein 1
      (AKAP1) exhibit increased sensitivity in the transient middle cerebral artery
      occlusion model of focal ischemia. At the ultrastructural level, AKAP1-/- mice
      have smaller mitochondria and increased contacts between mitochondria and the
      endoplasmic reticulum in the brain. Mechanistically, deletion of AKAP1
      dysregulates complex II of the electron transport chain, increases superoxide
      production, and impairs Ca2+ homeostasis in neurons subjected to excitotoxic
      glutamate. Ca2+ deregulation in neurons lacking AKAP1 can be attributed to loss
      of inhibitory phosphorylation of the mitochondrial fission enzyme dynamin-related
      protein 1 (Drp1) at the protein kinase A (PKA) site Ser637. Our results indicate
      that inhibition of Drp1-dependent mitochondrial fission by the outer
      mitochondrial AKAP1/PKA complex protects neurons from ischemic stroke by
      maintaining respiratory chain activity, inhibiting superoxide production, and
      delaying Ca2+ deregulation. They also provide the first genetic evidence that
      Drp1 inhibition may be of therapeutic relevance for the treatment of stroke and
      neurodegeneration.SIGNIFICANCE STATEMENT Previous work suggests that activation
      of dynamin-related protein 1 (Drp1) and mitochondrial fission contribute to
      ischemic injury in the brain. However, the specificity and efficacy of the
      pharmacological Drp1 inhibitor mdivi-1 that was used has now been discredited by
      several high-profile studies. Our report is timely and highly impactful because
      it provides the first evidence that genetic disinhibition of Drp1 via knock-out
      of the mitochondrial protein kinase A (PKA) scaffold AKAP1 exacerbates stroke
      injury in mice. Mechanistically, we show that electron transport deficiency,
      increased superoxide production, and Ca2+ overload result from genetic
      disinhibition of Drp1. In summary, our work settles current controversies
      regarding the role of mitochondrial fission in neuronal injury, provides
      mechanisms, and suggests that fission inhibitors hold promise as future
      therapeutic agents.

PMID- 30093536
TI  - 14-3-3 Proteins Reduce Cell-to-Cell Transfer and Propagation of Pathogenic alpha
      Synuclein.
AB  - alpha-Synuclein (alphasyn) is the key protein that forms neuronal aggregates in
      the neurodegenerative disorders Parkinson's disease (PD) and dementia with Lewy
      bodies. Recent evidence points to the prion-like spread of alphasyn from one
      brain region to another. Propagation of alphasyn is likely dependent on release,
      uptake, and misfolding. Under normal circumstances, this highly expressed brain
      protein functions normally without promoting pathology, yet the underlying
      endogenous mechanisms that prevent alphasyn spread are not understood. 14-3-3
      proteins are highly expressed brain proteins that have chaperone function and
      regulate protein trafficking. In this study, we investigated the potential role
      of the 14-3-3 proteins in the regulation of alphasyn spread using two models of
      alphasyn spread. In a paracrine alphasyn model, 14-3-3theta promoted release of
      alphasyn complexed with 14-3-3theta. Despite higher amounts of released alphasyn,
      extracellular alphasyn showed reduced oligomerization and seeding capability,
      reduced internalization, and reduced toxicity in primary mixed-gender mouse
      neurons. 14-3-3 inhibition reduced the amount of alphasyn released, yet released
      alphasyn was more toxic and demonstrated increased oligomerization, seeding
      capability, and internalization. In the preformed fibril model, 14-3-3 theta
      reduced alphasyn aggregation and neuronal death, whereas 14-3-3 inhibition
      enhanced alphasyn aggregation and neuronal death in primary mouse neurons. 14-3
      3s blocked alphasyn spread to distal chamber neurons not exposed directly to
      fibrils in multichamber, microfluidic devices. These findings point to 14-3-3s as
      a direct regulator of alphasyn propagation, and suggest that dysfunction of 14-3
      3 function may promote alphasyn pathology in PD and related
      synucleinopathies.SIGNIFICANCE STATEMENT Transfer of misfolded aggregates of
      alpha-synuclein from one brain region to another is implicated in the
      pathogenesis of Parkinson's disease and other synucleinopathies. This process is
      dependent on active release, internalization, and misfolding of alpha-synuclein.
      14-3-3 proteins are highly expressed chaperone proteins that interact with alpha
      synuclein and regulate protein trafficking. We used two different models in which
      toxicity is associated with cell-to-cell transfer of alpha-synuclein to test
      whether 14-3-3s impact alpha-synuclein toxicity. We demonstrate that 14-3-3theta
      reduces alpha-synuclein transfer and toxicity by inhibiting oligomerization,
      seeding capability, and internalization of alpha-synuclein, whereas 14-3-3
      inhibition accelerates the transfer and toxicity of alpha-synuclein in these
      models. Dysfunction of 14-3-3 function may be a critical mechanism by which alpha
      synuclein propagation occurs in disease.

PMID- 30093539
TI  - The Risk of Offspring Psychiatric Disorders in the Setting of Maternal Obesity
      and Diabetes.
AB  - BACKGROUND: Prenatal exposure to metabolic disturbances is associated with
      increased risk of offspring neurodevelopmental impairment and autism spectrum
      disorder, while little is known about the joint effect of maternal obesity and
      diabetes. With this study, we aim to assess the joint effect of maternal obesity
      and diabetes on the risk for offspring psychiatric and mild neurodevelopmental
      disorders. METHODS: Nationwide registries were used to link data of all live
      births in Finland between 2004 and 2014 (n = 649 043). Cox proportional hazards
      modeling adjusting for potential confounders was applied to estimate the effect
      of maternal obesity, pregestational diabetes mellitus (PGDM), and gestational
      diabetes mellitus, as well as their joint effects, on the outcomes of offspring
      psychiatric and mild neurodevelopmental diagnoses and offspring prescription of
      psychotropic drugs. RESULTS: Among mothers without diabetes, severely obese
      mothers had 67% to 88% increased risk of having a child with mild
      neurodevelopmental disorders (hazard risk ratio [HR] = 1.69; 95% confidence
      interval [CI] = 1.54-1.86), attention-deficit/hyperactivity disorder or conduct
      disorder (HR = 1.88; 95% CI = 1.58-2.23), and psychotic, mood, and stress-related
      disorders (HR = 1.67; 95% CI = 1.31-2.13) compared with mothers with a normal
      BMI. PGDM implied a further risk increase for all groups of psychiatric diagnoses
      with onset in childhood or adolescence in mothers with severe obesity. Marked
      effects were found particularly for autism spectrum disorder (HR = 6.49; 95% CI =
      3.08-13.69), attention-deficit/hyperactivity disorder and conduct disorder (HR =
      6.03; 95% CI = 3.23-11.24), and mixed disorders of conduct and emotions (HR =
      4.29; 95% CI = 2.14-8.60). Gestational diabetes mellitus did not increase the
      risk highly for these offspring disorders. CONCLUSIONS: Maternal PGDM combined
      with severe maternal obesity markedly increases the risk of several children's
      psychiatric and mild neurodevelopmental disorders.

PMID- 30093538
TI  - Neurotransmitter- and Release-Mode-Specific Modulation of Inhibitory Transmission
      by Group I Metabotropic Glutamate Receptors in Central Auditory Neurons of the
      Mouse.
AB  - Neuromodulation mediated by metabotropic glutamate receptors (mGluRs) regulates
      many brain functions. However, the functions of mGluRs in the auditory system
      under normal and diseased states are not well understood. The medial nucleus of
      the trapezoid body (MNTB) is a critical nucleus in the auditory brainstem nuclei
      involved in sound localization. In addition to the classical calyx excitatory
      inputs, MNTB neurons also receive synaptic inhibition and it remains entirely
      unknown how this inhibition is regulated. Here, using whole-cell voltage clamp in
      brain slices, we investigated group I mGluR (mGluR I)-mediated modulation of the
      glycinergic and GABAergic inputs to MNTB neurons in both WT mice and a fragile X
      syndrome (FXS) mouse model (both sexes) in which the fragile X mental retardation
      gene 1 is knocked out (Fmr1 KO), causing exaggerated activity of mGluR I and
      behavioral phenotypes. Activation of mGluR I by (RS)-3,5-dihydroxyphenylglycine
      (3,5-DHPG) increased the frequency and amplitude of glycinergic spontaneous IPSCs
      (sIPSCs) in both WT and Fmr1 KO neurons in a voltage-gated sodium channel
      dependent fashion, but did not modulate glycinergic evoked IPSCs (eIPSCs). In
      contrast, 3,5-DHPG did not affect GABAergic sIPSCs, but did suppress eIPSCs in WT
      neurons via endocannabinoid signaling. In the KO, the effect of 3,5-DHPG on
      GABAergic eIPSCs was highly variable, which supports the notion of impaired
      GABAergic signaling in the FXS model. The differential modulation of sIPSC and
      eIPSC and differential modulation of glycinergic and GABAergic transmission
      suggest distinct mechanisms responsible for spontaneous and evoked release of
      inhibitory transmitters and their modulation through the mGluR I signaling
      pathway.SIGNIFICANCE STATEMENT Neurons communicate with each other through the
      release of neurotransmitters, which assumes two basic modes, spontaneous and
      evoked release. These two release modes are believed to function using the same
      vesicle pool and machinery. Recent works have challenged this dogma, pointing to
      distinct vesicle release mechanisms underlying the two release modes. Here, we
      provide the first evidence in the central auditory system supporting this novel
      concept. We discovered neural-transmitter- and release-mode-specific
      neuromodulation of inhibitory transmission by metabotropic glutamate receptors
      and revealed part of the signaling pathways underlying this differential
      modulation. The results establish the foundation for a multitude of directions to
      study physiological significance of different release modes in auditory
      processing.

PMID- 30093541
TI  - Talk, Read, Sing: Early Language Exposure As an Overlooked Social Determinant of
      Health.

PMID- 30093540
TI  - Down Syndrome and the Risk of Severe RSV Infection: A Meta-analysis.
AB  - CONTEXT: Down syndrome (DS) is the most common chromosomal condition in live-born
      infants worldwide, and lower respiratory infection caused by respiratory
      syncytial virus (RSV) is a leading cause of hospital admissions. OBJECTIVE: To
      evaluate RSV-associated morbidity among children with DS compared with a
      population without DS. DATA SOURCES: Four electronic databases were searched.
      STUDY SELECTION: All cohorts or case-control studies of DS with an assessment of
      RSV infection and the associated morbidity or mortality were included without
      language restriction. DATA EXTRACTION: Two reviewers independently reviewed all
      studies. The primary outcomes were hospital admission and mortality. Secondary
      outcomes included length of hospital stay, oxygen requirement, ICU admission,
      need for respiratory support, and additional medication use. RESULTS: Twelve
      studies (n = 1 149 171) from 10 different countries met the inclusion criteria;
      10 studies were cohort studies, 1 study was retrospective, and 1 study had both
      designs. DS was associated with a higher risk of hospitalization (odds ratio
      [OR]: 8.69; 95% confidence interval [CI]: 7.33-10.30; I2 = 11%) and mortality
      (OR: 9.4; 95% CI: 2.26-39.15; I2 = 38%) compared with what was seen in controls.
      Children with DS had an increased length of hospital stay (mean difference: 4.73
      days; 95% CI: 2.12-7.33; I2 = 0%), oxygen requirement (OR: 6.53; 95% CI: 2.22
      19.19; I2 = 0%), ICU admission (OR: 2.56; 95% CI: 1.17-5.59; I2 = 0%), need for
      mechanical ventilation (OR: 2.56; 95% CI: 1.17-5.59; I2 = 0%), and additional
      medication use (OR: 2.65 [95% CI: 1.38-5.08; I2 = 0%] for systemic
      corticosteroids and OR: 5.82 [95% CI: 2.66-12.69; I2 = 0%] for antibiotics) than
      controls. LIMITATIONS: DS subgroups with and without other additional risk
      factors were not reported in all of the included studies. CONCLUSIONS: Children
      with DS had a significantly higher risk of severe RSV infection than children
      without DS.

PMID- 30093542
TI  - Woman in her 50s with shortness of breath on exertion.
AB  - CLINICAL INTRODUCTION: A 59-year-old woman visited an outpatient cardiology
      clinic due to shortness of breath on exertion. Physical examination showed no
      significant abnormality of vital signs. A III/VI systolic murmur was heard on the
      fourth intercostal space at the right sternal border. The majority of laboratory
      tests were normal. Chest X-ray showed a curved vessel shadow (figure 1A). Initial
      transthoracic echocardiography showed abnormal blood flow into the inferior vena
      cava (IVC) in the subxiphoid long axis view (figure 1B) and mild right heart
      dilatation (online supplementary figure 1). Transoesophageal echocardiography
      showed severe tricuspid regurgitation (online supplementary figure
      2).DC1SP110.1136/heartjnl-2018-313655.supp1Supplementary data
      DC2SP210.1136/heartjnl-2018-313655.supp2Supplementary data heartjnl;heartjnl-2018
      313655v1/F1F1F1Figure 1(A) Chest X-ray. (B) Colour Doppler image in the
      subxiphoid long axis view. QUESTION: What is the most likely underlying disease
      for the patient's shortness of breath on exertion? Pulmonary arteriovenous
      fistula.Pulmonary arterial hypertension.Lung cancer.Partial anomalous pulmonary
      venous connection.Isolated tricuspid regurgitation.

PMID- 30093543
TI  - Long-term outcomes of His bundle pacing in patients with heart failure with left
      bundle branch block.
AB  - OBJECTIVES: His bundle pacing (HBP) can potentially correct left bundle branch
      block (LBBB). We aimed to assess the efficacy of HBP to correct LBBB and long
      term clinical outcomes with HBP in patients with heart failure (HF). METHODS:
      This is an observational study of patients with HF with typical LBBB who were
      indicated for pacing therapy and were consecutively enrolled from one centre.
      Permanent HBP leads were implanted if the LBBB correction threshold was <3.5V/0.5
      ms or 3.0 V/1.0 ms. Pacing parameters, left ventricular ejection fraction (LVEF),
      left ventricular end-systolic volume (LVESV) and New York Heart Association
      (NYHA) Class were assessed during follow-up. RESULTS: In 74 enrolled patients
      (69.6+/-9.2 years and 43 men), LBBB correction was acutely achieved in 72 (97.3%)
      patients, and 56 (75.7%) patients received permanent HBP (pHBP) while 18 patients
      did not receive permanent HBP (non-permanent HBP), due to no LBBB correction
      (n=2), high LBBB correction thresholds (n=10) and fixation failure (n=6). The
      median follow-up period of pHBP was 37.1 (range 15.0-48.7) months. Thirty
      patients with pHBP had completed 3-year follow-up, with LVEF increased from
      baseline 32.4+/-8.9% to 55.9+/-10.7% (p<0.001), LVESV decreased from a baseline
      of 137.9+/-64.1 mL to 52.4+/-32.6 mL (p<0.001) and NYHA Class improvement from
      baseline 2.73+/-0.58 to 1.03+/-0.18 (p<0.001). LBBB correction threshold remained
      stable with acute threshold of 2.13+/-1.19 V/0.5 ms to 2.29+/-0.92 V/0.5 ms at 3
      year follow-up (p>0.05). CONCLUSIONS: pHBP improved LVEF, LVESV and NYHA Class in
      patients with HF with typical LBBB.

PMID- 30093544
TI  - British Cardiovascular Society Young Investigator Award: finalists 2018.

PMID- 30093545
TI  - Right ventricle to pulmonary artery coupling in patients undergoing transcatheter
      aortic valve implantation.
AB  - OBJECTIVES: To evaluate the prognostic value of the ratio between tricuspid
      annular plane systolic excursion (TAPSE)-pulmonary artery systolic pressure
      (PASP) as a determinant of right ventricular to pulmonary artery (RV-PA) coupling
      in patients undergoing transcatheter aortic valve replacement (TAVI). BACKGROUND:
      RV function and pulmonary hypertension (PH) are both prognostically important in
      patients receiving TAVI. RV-PA coupling has been shown to be prognostic important
      in patients with heart failure but not previously evaluated in TAVI patients.
      METHODS: Consecutive patients with severe aortic stenosis who received TAVI from
      July 2011 through January 2016 and with comprehensive baseline echocardiogram
      were included. All individual echocardiographic images and Doppler data were
      independently reviewed and blinded to the clinical information and outcomes. Cox
      models quantified the effect of TAPSE/PASP quartiles on subsequent all-cause
      mortality while adjusting for confounders. RESULTS: A total of 457 patients were
      included with mean age of 82.8+/-7.2 years, left ventricular ejection fraction
      (LVEF) 54%+/-13%, PASP 44+/-17 mm Hg. TAPSE/PASP quartiles showed a dose-response
      relationship with survival. This remained significant (HR for lowest quartile vs
      highest quartile=2.21, 95% CI 1.07 to 4.57, p=0.03) after adjusting for age,
      atrial fibrillation, LVEF, stroke volume index, Society of Thoracic Surgeons
      Predicted Risk of Mortality. CONCLUSION: Baseline TAPSE/PASP ratio is associated
      with all-cause mortality in TAVI patients as it evaluates RV systolic performance
      at a given degree of afterload. Incorporation of right-side unit into the risk
      stratification may improve optimal selection of patients for TAVI.

PMID- 30093546
TI  - Eighty-two-year-old man with a systolic murmur.
AB  - CLINICAL INTRODUCTION: An 82-year-old man with a history of coronary artery
      bypass surgery, hypertension and small bowel gastrointestinal stromal tumour
      underwent cardiac risk evaluation prior to surgical resection of his tumour. He
      was asymptomatic from a cardiovascular perspective, but his activity level was
      less than four metabolic equivalents. Physical examination was notable for a 2/6
      systolic murmur at the apex. ECG showed sinus rhythm. A transthoracic
      echocardiogram was performed (figure 1 and online supplementary video
      1).DC1SP110.1136/heartjnl-2018-313413.supp1Supplementary file 1
      heartjnl;104/22/1887/F1F1F1Figure 1Transthoracic echocardiography. (A) Mitral
      valve continuous wave Doppler and (B) tricuspid valve continuous wave Doppler.
      QUESTION: The findings in figure 1 are most likely due to which of the
      following?Atrioventricular conduction block.Acute severe aortic
      regurgitation.Patent ductus arteriosus.Atrial flutter.Severe mitral stenosis.

PMID- 30093547
TI  - Whole-genome bisulfite sequencing with improved accuracy and cost.
AB  - DNA methylation patterns in the genome both reflect and help to mediate
      transcriptional regulatory processes. The digital nature of DNA methylation,
      present or absent on each allele, makes this assay capable of quantifying events
      in subpopulations of cells, whereas genome-wide chromatin studies lack the same
      quantitative capacity. Testing DNA methylation throughout the genome is possible
      using whole-genome bisulfite sequencing (WGBS), but the high costs associated
      with the assay have made it impractical for studies involving more than limited
      numbers of samples. We have optimized a new transposase-based library preparation
      assay for the Illumina HiSeq X platform suitable for limited amounts of DNA and
      providing a major cost reduction for WGBS. By incorporating methylated cytosines
      during fragment end repair, we reveal an end-repair artifact affecting 1%-2% of
      reads that we can remove analytically. We show that the use of a high (G + C)
      content spike-in performs better than PhiX in terms of bisulfite sequencing
      quality. As expected, the loci with transposase-accessible chromatin are DNA
      hypomethylated and enriched in flanking regions by post-translational
      modifications of histones usually associated with positive effects on gene
      expression. Using these transposase-accessible loci to represent the cis
      regulatory loci in the genome, we compared the representation of these loci
      between WGBS and other genome-wide DNA methylation assays, showing WGBS to
      outperform substantially all of the alternatives. We conclude that it is now
      technologically and financially feasible to perform WGBS in larger numbers of
      samples with greater accuracy than previously possible.

PMID- 30093548
TI  - Hidden variation in polyploid wheat drives local adaptation.
AB  - Wheat has been domesticated into a large number of agricultural environments and
      has the ability to adapt to diverse environments. To understand this process, we
      survey genotype, repeat content, and DNA methylation across a bread wheat
      landrace collection representing global genetic diversity. We identify
      independent variation in methylation, genotype, and transposon copy number. We
      show that these, so far unexploited, sources of variation have had a significant
      impact on the wheat genome and that ancestral methylation states become
      preferentially "hard coded" as single nucleotide polymorphisms (SNPs) via 5
      methylcytosine deamination. These mechanisms also drive local adaption, impacting
      important traits such as heading date and salt tolerance. Methylation and
      transposon diversity could therefore be used alongside SNP-based markers for
      breeding.

PMID- 30093550
TI  - Ma2/d promotes myonuclear positioning and association with the sarcoplasmic
      reticulum.
AB  - The cytoplasm of striated myofibers contains a large number of membrane
      organelles, including sarcoplasmic reticulum (SR), T-tubules and the nuclear
      membrane. These organelles maintain a characteristic juxtaposition that appears
      to be essential for efficient inter-membranous exchange of RNA, proteins and
      ions. We found that the membrane-associated Muscle-specific alpha2/delta (Ma2/d)
      subunit of the Ca2+ channel complex localizes to the SR and T-tubules, and
      accumulates at the myonuclear surfaces. Furthermore, Ma2/d mutant larval muscles
      exhibit nuclear positioning defects, disruption of the nuclear-SR
      juxtapositioning, as well as impaired larval locomotion. Ma2/d localization at
      the nuclear membrane depends on the proper function of the nesprin ortholog
      Msp300 and the BAR domain protein Amphiphysin (Amph). Importantly, live imaging
      of muscle contraction in intact Drosophila larvae indicated altered distribution
      of Sarco/Endoplamic Reticulum Ca2+-ATPase (SERCA) around the myonuclei of Ma2/d
      mutant larvae. Co-immunoprecipitation analysis supports association between Ma2/d
      and Amph, and indirectly with Msp300. We therefore suggest that Ma2/d, in
      association with Msp300 and Amph, mediates interactions between the SR and the
      nuclear membrane.

PMID- 30093552
TI  - RPM-1 and DLK-1 regulate pioneer axon outgrowth by controlling Wnt signaling.
AB  - Axons must correctly reach their targets for proper nervous system function,
      although we do not fully understand the underlying mechanism, particularly for
      the first 'pioneer' axons. In C. elegans, AVG is the first neuron to extend an
      axon along the ventral midline, and this pioneer axon facilitates the proper
      extension and guidance of follower axons that comprise the ventral nerve cord.
      Here, we show that the ubiquitin ligase RPM-1 prevents the overgrowth of the AVG
      axon by repressing the activity of the DLK-1/p38 MAPK pathway. Unlike in damaged
      neurons, where this pathway activates CEBP-1, we find that RPM-1 and the DLK-1
      pathway instead regulate the response to extracellular Wnt cues in developing AVG
      axons. The Wnt LIN-44 promotes the posterior growth of the AVG axon. In the
      absence of RPM-1 activity, AVG becomes responsive to a different Wnt, EGL-20,
      through a mechanism that appears to be independent of canonical Fz-type
      receptors. Our results suggest that RPM-1 and the DLK-1 pathway regulate axon
      guidance and growth by preventing Wnt signaling crosstalk.

PMID- 30093553
TI  - Neurog3-dependent pancreas dysgenesis causes ectopic pancreas in Hes1 mutant
      mice.
AB  - Mutations in Hes1, a target gene of the Notch signalling pathway, lead to ectopic
      pancreas by a poorly described mechanism. Here, we use genetic inactivation of
      Hes1 combined with lineage tracing and live imaging to reveal an endodermal
      requirement for Hes1, and show that ectopic pancreas tissue is derived from the
      dorsal pancreas primordium. RNA-seq analysis of sorted E10.5 Hes1+/+ and Hes1-/-
      Pdx1-GFP+ cells suggested that upregulation of endocrine lineage genes in Hes1-/-
      embryos was the major defect and, accordingly, early pancreas morphogenesis was
      normalized, and the ectopic pancreas phenotype suppressed, in Hes1-/-Neurog3-/-
      embryos. In Mib1 mutants, we found a near total depletion of dorsal progenitors,
      which was replaced by an anterior Gcg+ extension. Together, our results
      demonstrate that aberrant morphogenesis is the cause of ectopic pancreas and that
      a part of the endocrine differentiation program is mechanistically involved in
      the dysgenesis. Our results suggest that the ratio of endocrine lineage to
      progenitor cells is important for morphogenesis and that a strong endocrinogenic
      phenotype without complete progenitor depletion, as seen in Hes1 mutants,
      provokes an extreme dysgenesis that causes ectopic pancreas.

PMID- 30093549
TI  - Type 1 Diabetes in Children and Adolescents: A Position Statement by the American
      Diabetes Association.

PMID- 30093556
TI  - Lung cancer staging: imagine fewer images.

PMID- 30093554
TI  - The replicative histone chaperone CAF1 is essential for the maintenance of
      identity and genome integrity in adult stem cells.
AB  - Chromatin packaging and modifications are important to define the identity of
      stem cells. How chromatin properties are retained over multiple cycles of stem
      cell replication, while generating differentiating progeny at the same time,
      remains a challenging question. The chromatin assembly factor CAF1 is a conserved
      histone chaperone, which assembles histones H3 and H4 onto newly synthesized DNA
      during replication and repair. Here, we have investigated the role of CAF1 in the
      maintenance of germline stem cells (GSCs) in Drosophila ovaries. We depleted
      P180, the large subunit of CAF1, in germ cells and found that it was required in
      GSCs to maintain their identity. In the absence of P180, GSCs still harbor stem
      cell properties but concomitantly express markers of differentiation. In
      addition, P180-depleted germ cells exhibit elevated levels of DNA damage and de
      repression of the transposable I element. These DNA damages activate p53- and
      Chk2-dependent checkpoints pathways, leading to cell death and female sterility.
      Altogether, our work demonstrates that chromatin dynamics mediated by CAF1 play
      an important role in both the regulation of stem cell identity and genome
      integrity.

PMID- 30093557
TI  - Airway smooth muscle may drive mucus hypersecretion in asthma.

PMID- 30093551
TI  - Minor spliceosome inactivation causes microcephaly, owing to cell cycle defects
      and death of self-amplifying radial glial cells.
AB  - Mutation in minor spliceosome components is linked to the developmental disorder
      microcephalic osteodysplastic primordial dwarfism type 1 (MOPD1). Here, we
      inactivated the minor spliceosome in the developing mouse cortex (pallium) by
      ablating Rnu11, which encodes the crucial minor spliceosome small nuclear RNA
      (snRNA) U11. Rnu11 conditional knockout mice were born with microcephaly, which
      was caused by the death of self-amplifying radial glial cells (RGCs), while
      intermediate progenitor cells and neurons were produced. RNA sequencing suggested
      that this cell death was mediated by upregulation of p53 (Trp53 - Mouse Genome
      Informatics) and DNA damage, which were both observed specifically in U11-null
      RGCs. Moreover, U11 loss caused elevated minor intron retention in genes
      regulating the cell cycle, which was consistent with fewer RGCs in S-phase and
      cytokinesis, alongside prolonged metaphase in RGCs. In all, we found that self
      amplifying RGCs are the cell type most sensitive to loss of minor splicing.
      Together, these findings provide a potential explanation of how disruption of
      minor splicing might cause microcephaly in MOPD1.

PMID- 30093558
TI  - Noninvasive ventilation for acute respiratory failure: the next step is to know
      when to stop.

PMID- 30093559
TI  - Lung cancer staging: imagine fewer images.

PMID- 30093555
TI  - Gli3 controls the onset of cortical neurogenesis by regulating the radial glial
      cell cycle through Cdk6 expression.
AB  - The cerebral cortex contains an enormous number of neurons, allowing it to
      perform highly complex neural tasks. Understanding how these neurons develop at
      the correct time and place and in accurate numbers constitutes a major challenge.
      Here, we demonstrate a novel role for Gli3, a key regulator of cortical
      development, in cortical neurogenesis. We show that the onset of neuron formation
      is delayed in Gli3 conditional mouse mutants. Gene expression profiling and cell
      cycle measurements indicate that shortening of the G1 and S phases in radial
      glial cells precedes this delay. Reduced G1 length correlates with an
      upregulation of the cyclin-dependent kinase gene Cdk6, which is directly
      regulated by Gli3. Moreover, pharmacological interference with Cdk6 function
      rescues the delayed neurogenesis in Gli3 mutant embryos. Overall, our data
      indicate that Gli3 controls the onset of cortical neurogenesis by determining the
      levels of Cdk6 expression, thereby regulating neuronal output and cortical size.

PMID- 30093560
TI  - Cancer-Associated MORC2-Mutant M276I Regulates an hnRNPM-Mediated CD44 Splicing
      Switch to Promote Invasion and Metastasis in Triple-Negative Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer,
      with a high propensity for distant metastasis and limited treatment options, yet
      its molecular underpinnings remain largely unknown. Microrchidia family CW-type
      zinc finger 2 (MORC2) is a newly identified chromatin remodeling protein whose
      mutations have been causally implicated in several neurologic disorders. Here, we
      report that a cancer-associated substitution of methionine to isoleucine at
      residue 276 (M276I) of MORC2 confers gain-of-function properties in the
      metastatic progression of TNBC. Expression of mutant MORC2 in TNBC cells
      increased cell migration, invasion, and lung metastasis without affecting cell
      proliferation and primary tumor growth compared with its wild-type counterpart.
      The M276I mutation enhanced binding of MORC2 to heterogeneous nuclear
      ribonucleoprotein M (hnRNPM), a component of the spliceosome machinery. This
      interaction promoted an hnRNPM-mediated splicing switch of CD44 from the
      epithelial isoform (CD44v) to the mesenchymal isoform (CD44s), ultimately driving
      epithelial-mesenchymal transition (EMT). Knockdown of hnRNPM reduced the binding
      of mutant MORC2 to CD44 pre-mRNA and reversed the mutant MORC2-induced CD44
      splicing switch and EMT, consequently impairing the migratory, invasive, and lung
      metastatic potential of mutant MORC2-expressing cells. Collectively, these
      findings provide the first functional evidence for the M276I mutation in
      promoting TNBC progression. They also establish the first mechanistic connection
      between MORC2 and RNA splicing and highlight the importance of deciphering unique
      patient-derived mutations for optimizing clinical outcomes of this highly
      heterogeneous disease.Significance: A gain-of-function effect of a single
      mutation on MORC2 promotes metastasis of triple-negative breast cancer by
      regulating CD44 splicing. Cancer Res; 78(20); 5780-92. (c)2018 AACR.

PMID- 30093562
TI  - Loss of MST/Hippo Signaling in a Genetically Engineered Mouse Model of Fusion
      Positive Rhabdomyosarcoma Accelerates Tumorigenesis.
AB  - A hallmark of fusion-positive alveolar rhabdomyosarcoma (aRMS) is the presence of
      a chromosomal translocation encoding the PAX3-FOXO1 fusion oncogene. Primary cell
      based modeling experiments have shown that PAX3-FOXO1 is necessary, but not
      sufficient for aRMS tumorigenesis, indicating additional molecular alterations
      are required to initiate and sustain tumor growth. Previously, we showed that
      PAX3-FOXO1-positive aRMS is promoted by dysregulated Hippo pathway signaling, as
      demonstrated by increased YAP1 expression and decreased MST activity. We
      hypothesized that ablating MST/Hippo signaling in a genetically engineered mouse
      model (GEMM) of aRMS would accelerate tumorigenesis. To this end, MST1/2-floxed
      (Stk3F/F;Stk4F/F ) mice were crossed with a previously established aRMS GEMM
      driven by conditional expression of Pax3:Foxo1 from the endogenous Pax3 locus and
      conditional loss of Cdkn2a in Myf6 (myogenic factor 6)-expressing cells. Compared
      with Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ controls,
      Stk3F/F;Stk4F/F;Pax3PF/PF;Cdkn2aF/F;Myf6ICN/+ animals displayed accelerated
      tumorigenesis (P < 0.0001) and increased tumor penetrance (88% vs. 27%). GEMM
      tumors were histologically consistent with aRMS. GEMM tumor-derived cell lines
      showed increased proliferation and invasion and decreased senescence and myogenic
      differentiation. These data suggest that loss of MST/Hippo signaling acts with
      Pax3:Foxo1 expression and Cdkn2a loss to promote tumorigenesis. The rapid onset
      and increased penetrance of tumorigenesis in this model provide a powerful tool
      for interrogating aRMS biology and screening novel therapeutics.Significance: A
      novel mouse model sheds light on the critical role of Hippo/MST downregulation in
      PAX3-FOXO1-positive rhabdomyosarcoma tumorigenesis. Cancer Res; 78(19); 5513-20.
      (c)2018 AACR.

PMID- 30093563
TI  - miR-652 Promotes Tumor Proliferation and Metastasis by Targeting RORA in
      Endometrial Cancer.
AB  - : Endometrial cancer is the most common gynecologic malignancy, whose incidence
      rate is on the rise. However, the underlying mechanisms of endometrial cancer are
      not very clear yet. miRNAs have been considered to be playing important roles in
      malignant behavior. Here, miR-652 was significantly upregulated in endometrial
      cancer, which correlated with shorter overall survival and earlier recurrence.
      Moreover, overexpression of miR-652 in endometrial cancer cells promoted
      proliferation, migration, and invasion in vitro and facilitated tumor growth and
      metastasis in vivo. In contrast, downregulation of miR-652 in endometrial cancer
      cells inhibited these processes both in vitro and in vivo. Mechanistically, miR
      652 promotes proliferation and metastasis through directly targeting RORA. Both
      mRNA and protein level of RORA were negatively related with miR-652 and
      overexpression of RORA can rescue the promotion effect of miR-652. Further
      experiments indicated miR-652 overexpression can activate the Wnt/beta-catenin
      pathway and RORA can downregulate beta-catenin and function as a tumor suppressor
      in endometrial cancer. Collectively, these findings demonstrate that miR-652
      functions as an oncomir in endometrial cancer. IMPLICATIONS: This study suggests
      that the miR-652 is a critical regulator of proliferation and metastasis in
      endometrial cancer and may serve as a therapeutic target.

PMID- 30093564
TI  - Digital PCR-Based T-cell Quantification-Assisted Deconvolution of the
      Microenvironment Reveals that Activated Macrophages Drive Tumor Inflammation in
      Uveal Melanoma.
AB  - : Uveal melanoma progression can be predicted by gene expression profiles
      enabling a clear subdivision between tumors with a good (class I) and a poor
      (class II) prognosis. Poor prognosis uveal melanoma can be subdivided by
      expression of immune-related genes; however, it is unclear whether this
      subclassification is justified; therefore, T cells in uveal melanoma specimens
      were quantified using a digital PCR approach. Absolute T-cell quantification
      revealed that T-cell influx is present in all uveal melanomas associated with a
      poor prognosis. However, this infiltrate is only accompanied by differential
      immune-related gene expression profiles in uveal melanoma with the highest T-cell
      infiltrate. Molecular deconvolution of the immune profile revealed that a large
      proportion of the T-cell-related gene expression signature does not originate
      from lymphocytes but is derived from other immune cells, especially macrophages.
      Expression of the lymphocyte-homing chemokine CXCL10 by activated macrophages
      correlated with T-cell infiltration and thereby explains the correlation of T
      cell numbers and macrophages. This was validated by in situ analysis of CXCL10 in
      uveal melanoma tissue with high T-cell counts. Surprisingly, CXCL10 or any of the
      other genes in the activated macrophage-cluster was correlated with reduced
      survival due to uveal melanoma metastasis. This effect was independent of the T
      cell infiltrate, which reveals a role for activated macrophages in metastasis
      formation independent of their role in tumor inflammation. IMPLICATIONS: The
      current report uses an innovative digital PCR method to study the immune
      environment and demonstrates that absolute T-cell quantification and expression
      profiles can dissect disparate immune components.

PMID- 30093565
TI  - A Novel Alternative Splicing Mechanism That Enhances Human 5-HT1A Receptor RNA
      Stability Is Altered in Major Depression.
AB  - The serotonin-1A (5-HT1A) receptor is a key regulator of serotonergic activity
      and is implicated in mood and emotion. However, its post-transcriptional
      regulation has never been studied in humans. In the present study, we show that
      the "intronless" human 5-HT1A gene (HTR1A) is alternatively spliced in its 3'
      UTR, yielding two novel splice variants. These variants lack a ~1.6 kb intron,
      which contains an microRNA-135 (miR135) target site. Unlike the human HTR1A, the
      mouse HTR1A lacks the splice donor/accepter sites. Thus, in the mouse HTR1A,
      splicing was not detected. The two spliced mRNAs are extremely stable, are
      resistant to miR135-induced downregulation, and have greater translational output
      than the unspliced variant. Moreover, alternative HTR1A RNA splicing is
      oppositely regulated by the splice factors PTBP1 and nSR100, which inhibit or
      enhance its splicing, respectively. In postmortem human brain tissue from both
      sexes, HTR1A mRNA splicing was prevalent and region-specific. Unspliced HTR1A was
      expressed more strongly in the hippocampus and midbrain versus the prefrontal
      cortex (PFC), and correlated with reduced levels of nSR100. Importantly, HTR1A
      RNA splicing and nSR100 levels were reduced in the PFC of individuals with major
      depression compared with controls. Our unexpected findings uncover a novel
      mechanism to regulate HTR1A gene expression through alternative splicing of
      microRNA sites. Altered levels of splice factors could contribute to changes in
      regional and depression-related gene expression through alternative
      splicing.SIGNIFICANCE STATEMENT Alternative splicing, which is prevalent in brain
      tissue, increases gene diversity. The serotonin-1A receptor gene (HTR1A) is a
      regulator of serotonin, which is implicated in mood and emotion. Here we show
      that human HTR1A RNA is alternately spliced. Splicing removes a microRNA site to
      generate ultrastable RNA and increase HTR1A expression. This splicing varies in
      different brain regions and is reduced in major depression. We also identify
      specific splice factors for HTR1A RNA, showing they are also reduced in
      depression. Thus, we describe a novel mechanism to regulate gene expression
      through splicing. Altered levels of splice factors could contribute to depression
      by changing gene expression.

PMID- 30093561
TI  - Inhibition of the Stromal p38MAPK/MK2 Pathway Limits Breast Cancer Metastases and
      Chemotherapy-Induced Bone Loss.
AB  - The role of the stromal compartment in tumor progression is best illustrated in
      breast cancer bone metastases, where the stromal compartment supports tumor
      growth, albeit through poorly defined mechanisms. p38MAPKalpha is frequently
      expressed in tumor cells and surrounding stromal cells, and its expression levels
      correlate with poor prognosis. This observation led us to investigate whether
      inhibition of p38MAPKalpha could reduce breast cancer metastases in a clinically
      relevant model. Orally administered, small-molecule inhibitors of p38MAPKalpha or
      its downstream kinase MK2 each limited outgrowth of metastatic breast cancer
      cells in the bone and visceral organs. This effect was primarily mediated by
      inhibition of the p38MAPKalpha pathway within the stromal compartment. Beyond
      effectively limiting metastatic tumor growth, these inhibitors reduced tumor
      associated and chemotherapy-induced bone loss, which is a devastating comorbidity
      that drastically affects quality of life for patients with cancer. These data
      underscore the vital role played by stromal-derived factors in tumor progression
      and identify the p38MAPK-MK2 pathway as a promising therapeutic target for
      metastatic disease and prevention of tumor-induced bone loss.Significance:
      Pharmacologically targeting the stromal p38MAPK-MK2 pathway limits metastatic
      breast cancer growth, preserves bone quality, and extends survival. Cancer Res;
      78(19); 5618-30. (c)2018 AACR.

PMID- 30093567
TI  - Unraveling the Interaction between Carboxylesterase 1c and the Antibody-Drug
      Conjugate SYD985: Improved Translational PK/PD by Using Ces1c Knockout Mice.
AB  - Carboxylesterase 1c (CES1c) is responsible for linker-drug instability and poor
      pharmacokinetics (PK) of several antibody-drug conjugates (ADC) in mice, but not
      in monkeys or humans. Preclinical development of these ADCs could be improved if
      the PK in mice would more closely resemble that of humans and is not affected by
      an enzyme that is irrelevant for humans. SYD985, a HER2-targeting ADC based on
      trastuzumab and linker-drug vc-seco-DUBA, is also sensitive to CES1c. In the
      present studies, we first focused on the interaction between CES1c and SYD985 by
      size- exclusion chromatography, Western blotting, and LC/MS-MS analysis, using
      recombinant CES1c and plasma samples. Intriguingly, CES1c activity not only
      results in release of the active toxin DUBA but also in formation of a covalent
      bond between CES1c and the linker of vc-seco-DUBA. Mass spectrometric studies
      enabled identification of the CES1c cleavage site on the linker-drug and the
      structure of the CES1c adduct. To assess the in vivo impact, CES1c-/- SCID mice
      were generated that showed stable PK for SYD985, comparable to that in monkeys
      and humans. Patient-derived xenograft (PDX) studies in these mice showed enhanced
      efficacy compared with PDX studies in CES1c+/+ mice and provided a more accurate
      prediction of clinical efficacy of SYD985, hence delivering better quality data.
      It seems reasonable to assume that CES1c-/- SCID mice can increase quality in ADC
      development much broader for all ADCs that carry linker-drugs susceptible to
      CES1c, without the need of chemically modifying the linker-drug to specifically
      increase PK in mice. Mol Cancer Ther; 17(11); 2389-98. (c)2018 AACR.

PMID- 30093566
TI  - Mast Cells in the Developing Brain Determine Adult Sexual Behavior.
AB  - Many sex differences in brain and behavior are programmed during development by
      gonadal hormones, but the cellular mechanisms are incompletely understood. We
      found that immune-system-derived mast cells are a primary target for the
      masculinizing hormone estradiol and that mast cells are in turn primary mediators
      of brain sexual differentiation. Newborn male rats had greater numbers and more
      activated mast cells in the preoptic area (POA), a brain region essential for
      male copulatory behavior, than female littermates during the critical period for
      sexual differentiation. Inhibiting mast cells with a stabilizing agent blunted
      the masculinization of both POA neuronal and microglial morphology and adult sex
      behavior, whereas activating mast cells in females, even though fewer in number,
      induced masculinization. Treatment of newborn females with a masculinizing dose
      of estradiol increased mast cell number and induced mast cells to release
      histamine, which then stimulated microglia to release prostaglandins and thereby
      induced male-typical synaptic patterning. These findings identify a novel non
      neuronal origin of brain sex differences and resulting motivated
      behaviors.SIGNIFICANCE STATEMENT We found that immune-system-derived mast cells
      are a primary target for the masculinizing hormone estradiol and that mast cells
      are in turn primary mediators of brain sexual differentiation. These findings
      identify a novel non-neuronal origin of brain sex differences and resulting
      motivated behaviors.

PMID- 30093569
TI  - Maternal dietary antioxidant intake in pregnancy and childhood respiratory and
      atopic outcomes: birth cohort study.
AB  - Evidence for a possible protective effect of maternal dietary antioxidant intake
      during pregnancy on childhood asthma and other atopic outcomes is conflicting,
      and associations with childhood lung function have been little studied.In the
      Avon Longitudinal Study of Parents and Children, we analysed associations between
      maternal intake of fruits, vegetables, vitamins C and E, carotene, zinc, and
      selenium in pregnancy and current doctor-diagnosed asthma, atopy and lung
      function in 8915 children at age 7-9 years. Potential modification of
      associations by maternal smoking and common maternal antioxidant gene
      polymorphisms was explored to strengthen causal inference.After controlling for
      confounders, positive associations were observed between maternal intake of zinc
      and childhood forced expiratory volume in 1 s and forced vital capacity
      (difference in age-, height- and sex-adjusted sd units per quartile increase in
      maternal dietary zinc intake beta 0.05 (95% CI 0.01-0.08); ptrend=0.01 and 0.05
      (95% CI 0.02-0.09); ptrend=0.005, respectively). Weak evidence was found for an
      interaction between maternal zinc intake and maternal glutathione S-transferase
      GSTM1 genotype on childhood forced vital capacity (pinteraction=0.05);
      association among the GSTM1 null group beta 0.11 (95% CI 0.05-0.17);
      ptrend=0.001.Our results suggest that a higher maternal intake of zinc during
      pregnancy may be associated with better lung function in the offspring.

PMID- 30093570
TI  - Exercise pulmonary haemodynamic response predicts outcomes in fibrotic lung
      disease.

PMID- 30093571
TI  - Evaluation of the airway microbiome in nontuberculous mycobacteria disease.
AB  - Aspiration is associated with nontuberculous mycobacterial (NTM) pulmonary
      disease and airway dysbiosis is associated with increased inflammation. We
      examined whether NTM disease was associated with a distinct airway microbiota and
      immune profile.297 oral wash and induced sputum samples were collected from 106
      participants with respiratory symptoms and imaging abnormalities compatible with
      NTM. Lower airway samples were obtained in 20 participants undergoing
      bronchoscopy. 16S rRNA gene and nested mycobacteriome sequencing approaches
      characterised microbiota composition. In addition, inflammatory profiles of lower
      airway samples were examined.The prevalence of NTM+ cultures was 58%. Few changes
      were noted in microbiota characteristics or composition in oral wash and sputum
      samples among groups. Among NTM+ samples, 27% of the lower airway samples were
      enriched with Mycobacterium A mycobacteriome approach identified Mycobacterium in
      a greater percentage of samples, including some nonpathogenic strains. In NTM+
      lower airway samples, taxa identified as oral commensals were associated with
      increased inflammatory biomarkers.The 16S rRNA gene sequencing approach is not
      sensitive in identifying NTM among airway samples that are culture-positive.
      However, associations between lower airway inflammation and microbiota signatures
      suggest a potential role for these microbes in the inflammatory process in NTM
      disease.

PMID- 30093568
TI  - MERTK Mediates Intrinsic and Adaptive Resistance to AXL-targeting Agents.
AB  - The TAM (TYRO3, AXL, MERTK) family receptor tyrosine kinases (RTK) play an
      important role in promoting growth, survival, and metastatic spread of several
      tumor types. AXL and MERTK are overexpressed in head and neck squamous cell
      carcinoma (HNSCC), triple-negative breast cancer (TNBC), and non-small cell lung
      cancer (NSCLC), malignancies that are highly metastatic and lethal. AXL is the
      most well-characterized TAM receptor and mediates resistance to both conventional
      and targeted cancer therapies. AXL is highly expressed in aggressive tumor types,
      and patients with cancer are currently being enrolled in clinical trials testing
      AXL inhibitors. In this study, we analyzed the effects of AXL inhibition using a
      small-molecule AXL inhibitor, a monoclonal antibody (mAb), and siRNA in HNSCC,
      TNBC, and NSCLC preclinical models. Anti-AXL-targeting strategies had limited
      efficacy across these different models that, our data suggest, could be
      attributed to upregulation of MERTK. MERTK expression was increased in cell lines
      and patient-derived xenografts treated with AXL inhibitors and inhibition of
      MERTK sensitized HNSCC, TNBC, and NSCLC preclinical models to AXL inhibition.
      Dual targeting of AXL and MERTK led to a more potent blockade of downstream
      signaling, synergistic inhibition of tumor cell expansion in culture, and reduced
      tumor growth in vivo Furthermore, ectopic overexpression of MERTK in AXL
      inhibitor-sensitive models resulted in resistance to AXL-targeting strategies.
      These observations suggest that therapeutic strategies cotargeting both AXL and
      MERTK could be highly beneficial in a variety of tumor types where both receptors
      are expressed, leading to improved survival for patients with lethal
      malignancies. Mol Cancer Ther; 17(11); 2297-308. (c)2018 AACR.

PMID- 30093572
TI  - Physical activity as a moderator for obstructive sleep apnoea and cardiometabolic
      risk in the EPISONO study.
AB  - Obstructive sleep apnoea (OSA) is positively associated with cardiometabolic
      diseases; however, high levels of physical activity could decrease the incidence
      of OSA and associated comorbidities.In this study we aimed to examine the
      incidence of OSA in relation to physical activity, and its role as a protective
      factor in individuals with OSA on the incidence of cardiometabolic diseases, in
      an 8-9-year follow-up study. We analysed data of 658 volunteers from the Sao
      Paulo Epidemiologic Sleep Study (EPISONO), a cohort study of individuals aged 20
      80 years, collected through polysomnography, the International Physical Activity
      Questionnaire and an assessment of cardiometabolic profile.Active subjects had a
      lower risk of developing OSA compared with nonactive subjects (relative risk
      0.877, 95% CI 0.296-0.855) and there was a reduced risk of developing type 2
      diabetes mellitus in active/apnoeic subjects (relative risk 0.493, 95% CI 0.252
      0.961) compared with nonactive subjects. Metabolic equivalent was negatively
      associated to cardiometabolic markers, such as C-reactive protein (exp(B)=0.720;
      p=0.001), interleukin-6 (exp(B)=0.991; p=0.03), insulin (exp(B)=0.982; p=0.03),
      triglycerides (exp(B)=0.997; p<0.001), homeostasis model assessment for insulin
      resistance (exp(B)<=0.946; p<0.024), quantitative insulin sensitivity check index
      (exp(B)=992.4; p<0.001) and mean arterial pressure (exp(B)=0.987;
      p=0.001).Physical activity was a protective factor against type 2 diabetes
      mellitus in apnoeic individuals; moreover, being active reduced the risk of
      developing OSA and was associated with a better cardiometabolic profile.

PMID- 30093573
TI  - The vitamin D binding protein axis modifies disease severity in
      lymphangioleiomyomatosis.
AB  - Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung
      function is variable, making appropriate targeting of therapy difficult. We used
      unbiased serum proteomics to identify markers associated with outcome in LAM.101
      women with LAM and 22 healthy controls were recruited from the National Centre
      for LAM in the UK. 152 DNA and serum samples with linked lung function and
      outcome data were obtained from patients in the National Heart, Lung and Blood
      Institute LAM Registry in the USA. Proteomic analysis was performed on a
      discovery cohort of 50 LAM and 20 control serum samples using a SCIEX SWATH mass
      spectrometric workflow. Protein levels were quantitated by ELISA and single
      nucleotide polymorphisms in GC (group-specific component) encoding vitamin D
      binding protein (VTDB) were genotyped.Proteomic analysis showed VTDB was 2.6-fold
      lower in LAM than controls. Serum VTDB was lower in progressive compared with
      stable LAM (p=0.001) and correlated with diffusing capacity of the lung for
      carbon monoxide (p=0.01). Median time to death or lung transplant was reduced by
      46 months in those with CC genotypes at rs4588 and 38 months in those with non-A
      containing haplotypes at rs7041/4588 (p=0.014 and 0.008, respectively).The VTDB
      axis is associated with disease severity and outcome, and GC genotype could help
      predict transplant-free survival in LAM.

PMID- 30093574
TI  - Comment on "Unexpected reversal of C3 versus C4 grass response to elevated CO2
      during a 20-year field experiment".
AB  - Reich et al (Reports, 20 April 2018, p. 317) assert that the responses of C3 and
      C4 grass biomass to elevated CO2 "challenge the current C3-C4 [elevated CO2]
      paradigm," but these responses can be explained by the natural history of the
      experimental plants and soils without challenging this paradigm.

PMID- 30093575
TI  - Response to Comment on "Unexpected reversal of C3 versus C4 grass response to
      elevated CO2 during a 20-year field experiment".
AB  - Wolf and Ziska suggest that soil and species attributes can explain an unexpected
      20-year reversal of C3-C4 grass responses to elevated CO2 This is consistent with
      our original interpretation; however, we disagree with the assertion that such
      explanations somehow render our results irrelevant for questioning a long
      standing paradigm of plant response to CO2 based on C3-C4 differences in
      photosynthetic pathway.

PMID- 30093576
TI  - Dissipative Kerr solitons in optical microresonators.
AB  - The development of compact, chip-scale optical frequency comb sources
      (microcombs) based on parametric frequency conversion in microresonators has seen
      applications in terabit optical coherent communications, atomic clocks, ultrafast
      distance measurements, dual-comb spectroscopy, and the calibration of
      astophysical spectrometers and have enabled the creation of photonic-chip
      integrated frequency synthesizers. Underlying these recent advances has been the
      observation of temporal dissipative Kerr solitons in microresonators, which
      represent self-enforcing, stationary, and localized solutions of a damped,
      driven, and detuned nonlinear Schrodinger equation, which was first introduced to
      describe spatial self-organization phenomena. The generation of dissipative Kerr
      solitons provide a mechanism by which coherent optical combs with bandwidth
      exceeding one octave can be synthesized and have given rise to a host of
      phenomena, such as the Stokes soliton, soliton crystals, soliton switching, or
      dispersive waves. Soliton microcombs are compact, are compatible with wafer-scale
      processing, operate at low power, can operate with gigahertz to terahertz line
      spacing, and can enable the implementation of frequency combs in remote and
      mobile environments outside the laboratory environment, on Earth, airborne, or in
      outer space.

PMID- 30093578
TI  - News at a glance.

PMID- 30093579
TI  - New geological age comes under fire.

PMID- 30093577
TI  - Health of the Hajj.

PMID- 30093580
TI  - March of Dimes curtails support for researchers.

PMID- 30093582
TI  - Hope blooms for Hawaii's iconic native tree.

PMID- 30093581
TI  - Hybrids spawned Lake Victoria's rich fish diversity.

PMID- 30093583
TI  - Infrared method could safely identify cells.

PMID- 30093584
TI  - Control freaks.

PMID- 30093585
TI  - Measuring Earth's rivers.

PMID- 30093586
TI  - Phase changes in neurotransmission.

PMID- 30093588
TI  - Tighter lymphatic junctions prevent obesity.

PMID- 30093587
TI  - Ultrahigh thermal conductivity confirmed in boron arsenide.

PMID- 30093589
TI  - The future of humans as model organisms.

PMID- 30093590
TI  - Building an evidence base for stakeholder engagement.

PMID- 30093591
TI  - Protected land: Many factors shape success.

PMID- 30093592
TI  - Protected land: Threat of invasive species.

PMID- 30093593
TI  - Response.

PMID- 30093594
TI  - The role of electron-electron interactions in two-dimensional Dirac fermions.
AB  - The role of electron-electron interactions in two-dimensional Dirac fermion
      systems remains enigmatic. Using a combination of nonperturbative numerical and
      analytical techniques that incorporate both the contact and long-range parts of
      the Coulomb interaction, we identify the two previously discussed regimes: a
      Gross-Neveu transition to a strongly correlated Mott insulator and a semimetallic
      state with a logarithmically diverging Fermi velocity accurately described by the
      random phase approximation. We predict that experimental realizations of Dirac
      fermions span this crossover and that this determines whether the Fermi velocity
      is increased or decreased by interactions. We explain several long-standing
      mysteries, including why the observed Fermi velocity in graphene is consistently
      about 20% larger than values obtained from ab initio calculations and why
      graphene on different substrates shows different behaviors.

PMID- 30093595
TI  - Opioid prescribing decreases after learning of a patient's fatal overdose.
AB  - Most opioid prescription deaths occur among people with common conditions for
      which prescribing risks outweigh benefits. General psychological insights offer
      an explanation: People may judge risk to be low without available personal
      experiences, may be less careful than expected when not observed, and may falter
      without an injunction from authority. To test these hypotheses, we conducted a
      randomized trial of 861 clinicians prescribing to 170 persons who subsequently
      suffered fatal overdoses. Clinicians in the intervention group received
      notification of their patients' deaths and a safe prescribing injunction from
      their county's medical examiner, whereas physicians in the control group did not.
      Milligram morphine equivalents in prescriptions filled by patients of letter
      recipients versus controls decreased by 9.7% (95% confidence interval: 6.2 to
      13.2%; P < 0.001) over 3 months after intervention. We also observed both fewer
      opioid initiates and fewer high-dose opioid prescriptions by letter recipients.

PMID- 30093596
TI  - Ancient convergent losses of Paraoxonase 1 yield potential risks for modern
      marine mammals.
AB  - Mammals diversified by colonizing drastically different environments, with each
      transition yielding numerous molecular changes, including losses of protein
      function. Though not initially deleterious, these losses could subsequently carry
      deleterious pleiotropic consequences. We have used phylogenetic methods to
      identify convergent functional losses across independent marine mammal lineages.
      In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages,
      while remaining intact in all terrestrial mammals. These lesions coincide with
      PON1 enzymatic activity loss in marine species' blood plasma. This convergent
      loss is likely explained by parallel shifts in marine ancestors' lipid metabolism
      and/or bloodstream oxidative environment affecting PON1's role in fatty acid
      oxidation. PON1 loss also eliminates marine mammals' main defense against
      neurotoxicity from specific man-made organophosphorus compounds, implying
      potential risks in modern environments.

PMID- 30093600
TI  - How to start a research lab.

PMID- 30093601
TI  - An update of Wnt signalling in endometrial cancer and its potential as a
      therapeutic target.
AB  - Endometrial cancer is the most common gynaecological malignancy in developed
      nations, and its prevalence is rising as women defer or decide not to have
      children and as obesity rises, both key risk factors. Despite this, treatment
      options remain limited, particularly for advanced or refractory disease. New
      genomic analyses have revealed distinct mutational profiles with therapeutic and
      prognostic potential. Wnt signalling, which is pivotal in embryogenesis, healing
      and homeostasis, is of importance in the endometrium and has been linked to
      carcinogenesis. This review aims to update and discuss the current evidence for
      the role of beta-catenin dependent and independent Wnt signalling, including the
      ROR receptors in the endometrium and its potential as a therapeutic target, in
      light of recent trials of Wnt-targeted therapy in multiple tumour types.

PMID- 30093597
TI  - Single-cell transcriptomes from human kidneys reveal the cellular identity of
      renal tumors.
AB  - Messenger RNA encodes cellular function and phenotype. In the context of human
      cancer, it defines the identities of malignant cells and the diversity of tumor
      tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and
      normal tissue from fetal, pediatric, and adult kidneys. We matched childhood
      Wilms tumor with specific fetal cell types, thus providing evidence for the
      hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell
      carcinoma, we identified a canonical cancer transcriptome that matched a little
      known subtype of proximal convoluted tubular cell. Analyses of the tumor
      composition defined cancer-associated normal cells and delineated a complex
      vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal
      the precise cellular identities and compositions of human kidney tumors.

PMID- 30093598
TI  - Lacteal junction zippering protects against diet-induced obesity.
AB  - Excess dietary lipid uptake causes obesity, a major global health problem.
      Enterocyte-absorbed lipids are packaged into chylomicrons, which enter the
      bloodstream through intestinal lymphatic vessels called lacteals. Here, we show
      that preventing lacteal chylomicron uptake by inducible endothelial genetic
      deletion of Neuropilin1 (Nrp1) and Vascular endothelial growth factor receptor 1
      (Vegfr1; also known as Flt1) renders mice resistant to diet-induced obesity.
      Absence of NRP1 and FLT1 receptors increased VEGF-A bioavailability and signaling
      through VEGFR2, inducing lacteal junction zippering and chylomicron
      malabsorption. Restoring permeable lacteal junctions by VEGFR2 and vascular
      endothelial (VE)-cadherin signaling inhibition rescued chylomicron transport in
      the mutant mice. Zippering of lacteal junctions by disassembly of cytoskeletal VE
      cadherin anchors prevented chylomicron uptake in wild-type mice. These data
      suggest that lacteal junctions may be targets for preventing dietary fat uptake.

PMID- 30093602
TI  - Slab2, a comprehensive subduction zone geometry model.
AB  - Subduction zones are home to the most seismically active faults on the planet.
      The shallow megathrust interfaces of subduction zones host Earth's largest
      earthquakes and are likely the only faults capable of magnitude 9+ ruptures.
      Despite these facts, our knowledge of subduction zone geometry-which likely plays
      a key role in determining the spatial extent and ultimately the size of
      subduction zone earthquakes-is incomplete. We calculated the three-dimensional
      geometries of all seismically active global subduction zones. The resulting
      model, called Slab2, provides a uniform geometrical analysis of all currently
      subducting slabs.

PMID- 30093599
TI  - Apoptosis propagates through the cytoplasm as trigger waves.
AB  - Apoptosis is an evolutionarily conserved form of programmed cell death critical
      for development and tissue homeostasis in animals. The apoptotic control network
      includes several positive feedback loops that may allow apoptosis to spread
      through the cytoplasm in self-regenerating trigger waves. We tested this
      possibility in cell-free Xenopus laevis egg extracts and observed apoptotic
      trigger waves with speeds of ~30 micrometers per minute. Fractionation and
      inhibitor studies implicated multiple feedback loops in generating the waves.
      Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers
      per minute, which were tightly correlated with caspase activation. Thus,
      apoptosis spreads through trigger waves in both extracts and intact cells. Our
      findings show how apoptosis can spread over large distances within a cell and
      emphasize the general importance of trigger waves in cell signaling.

PMID- 30093603
TI  - Organic and solution-processed tandem solar cells with 17.3% efficiency.
AB  - Although organic photovoltaic (OPV) cells have many advantages, their performance
      still lags far behind that of other photovoltaic platforms. A fundamental reason
      for their low performance is the low charge mobility of organic materials,
      leading to a limit on the active-layer thickness and efficient light absorption.
      In this work, guided by a semi-empirical model analysis and using the tandem cell
      strategy to overcome such issues, and taking advantage of the high diversity and
      easily tunable band structure of organic materials, a record and certified 17.29%
      power conversion efficiency for a two-terminal monolithic solution-processed
      tandem OPV is achieved.

PMID- 30093605
TI  - Structure of the human PKD1-PKD2 complex.
AB  - Mutations in two genes, PKD1 and PKD2, account for most cases of autosomal
      dominant polycystic kidney disease, one of the most common monogenetic disorders.
      Here we report the 3.6-angstrom cryo-electron microscopy structure of truncated
      human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated
      ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet
      noncanonical, transient receptor potential (TRP) channel architecture. The S6
      helix in PKD1 is broken in the middle, with the extracellular half, S6a,
      resembling pore helix 1 in a typical TRP channel. Three positively charged,
      cavity-facing residues on S6b may block cation permeation. In addition to the
      VGIC, a five-transmembrane helix domain and a cytosolic PLAT domain were resolved
      in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting
      the function and disease mechanisms of the PKD proteins.

PMID- 30093606
TI  - Success Rate of Fungal Peri-Prosthetic Joint Infection Treated by 2-Stage
      Revision and Potential Risk Factors of Treatment Failure: A Retrospective Study.
AB  - BACKGROUND The aim of this study was to investigate the success rate of fungal
      peri-prosthetic joint infection treated by 2-stage revision and related factors
      of treatment failure to offer a better treatment protocol. MATERIAL AND METHODS
      We reviewed 18 joints (13 knees and 5 hips) of 17 patients (10 women and 7 men)
      diagnosed with fungal peri-prosthetic joint infection from January 2000 to June
      2015 at our institute. The mean follow-up was 65.1 months (range, 25-129 months).
      All joints were treated with complete debridement, implantation of antifungal
      loaded cement spacers, at least 6 weeks of parenteral antifungal agents, and
      delayed reimplantation. RESULTS Notably, 15 joints were infected with Candida,
      and molds were isolated in 3 joints. The median duration of resection
      arthroplasty and reimplantation was 33.9 weeks (range, 12-132 weeks). Thirteen
      (10 knees and 3 hips, 72.2%) of the 18 joints (13 knees and 5 hips) had no
      recurrent or persistent infection, while the remaining 5 joints (3 knees and 2
      hips, 27.8%) failed to control infection after reimplantation of prosthesis or
      spacer. The long interval between prosthesis resection and reimplantation (69
      weeks vs. 23.1 weeks, p=0.240) and mixed bacterial infection (80% vs. 46.2%,
      p=0.314) were associated with higher failure rate. CONCLUSIONS Debridement with
      the retention of the prosthesis is not an ideal treatment protocol for fungal
      peri-prosthetic joint infection; thus, a two-stage revision could be valid. We
      suggest that 6 weeks of parenteral antifungal agents are necessary, and 6
      subsequent weeks of oral antifungal treatment is also important. We do not
      recommend that the two-stage revision be performed on patients who have more than
      2 host risk factors.

PMID- 30093604
TI  - Developmental barcoding of whole mouse via homing CRISPR.
AB  - In vivo barcoding using nuclease-induced mutations is a powerful approach for
      recording biological information, including developmental lineages; however, its
      application in mammalian systems has been limited. We present in vivo barcoding
      in the mouse with multiple homing guide RNAs that each generate hundreds of
      mutant alleles and combine to produce an exponential diversity of barcodes.
      Activation upon conception and continued mutagenesis through gestation resulted
      in developmentally barcoded mice wherein information is recorded in lineage
      specific mutations. We used these recordings for reliable post hoc reconstruction
      of the earliest lineages and investigation of axis development in the brain. Our
      results provide an enabling and versatile platform for in vivo barcoding and
      lineage tracing in a mammalian model system.

PMID- 30093607
TI  - Tacrolimus Granules for Oral Suspension as Post-Transplant Immunosuppression in
      Routine Medical Practice in France: The OPTIMOD Study.
AB  - BACKGROUND Different pharmaceutical forms of oral tacrolimus allow tailored
      administration. The granular formulation facilitates accurate dose adjustment of
      tacrolimus according to patient characteristics, such as weight, or potential
      concomitant drug interactions. Currently, there are no data describing the use of
      tacrolimus granules in transplant recipients in France. MATERIAL AND METHODS
      OPTIMOD was a 6-month prospective, observational multicenter study that aimed to
      describe patient characteristics and conditions of use of tacrolimus granules.
      The 25 participating centers enrolled patients at time of tacrolimus granules
      initiation and were to collect patient and treatment data at initiation and after
      6 months of follow-up. All analyses were descriptive. RESULTS Of 61 patients
      included, 55.7% were children (mainly kidney graft recipients) and 44.3% were
      adults (mostly lung graft recipients). Overall, 24.6% of patients (all children)
      initiated tacrolimus granules immediately post-transplant; the remaining 75.4%
      converted to tacrolimus granules from ciclosporin or immediate-release tacrolimus
      hard capsules. The main reasons for initiating tacrolimus granules, irrespective
      of whether first- or second-line therapy, were to offset potential drug-drug
      interactions in adults by adjusting dose, and to adapt to the particular needs of
      children as patients. Most patients (78.7%) underwent >=1 dose modification
      during follow-up. Eleven rejection episodes occurred during follow-up, of which
      none led to graft loss. The adverse-event profile of the tacrolimus granules was
      similar to that of other tacrolimus formulations and 7 treatment-related adverse
      events were recorded. CONCLUSIONS Results suggest that tacrolimus granules are
      well tolerated and effective in preventing transplant rejection when administered
      in routine practice in France.

PMID- 30093608
TI  - Restoration of Balance and Unilateral Hearing Using Alternating and Filtering
      Auditory Training in Shunt-Treated Hydrocephalus Following Subarachnoid
      Hemorrhage: A Case Report.
AB  - BACKGROUND Although rehabilitation for balance disorders is commonly undertaken
      following a stroke, hearing dysfunction is rarely investigated, even though
      hearing loss affects the ability to maintain balance. This report presents a case
      of restoration of balance and unilateral hearing using an alternating and
      filtering auditory training (AFAT) protocol in a patient with subarachnoid
      hemorrhage (SAH) and shunt-treated hydrocephalus. CASE REPORT A 54-year-old woman
      with a five-month history of SAH due to a ruptured aneurysm in the anterior
      communicating artery and hydrocephalus treated with a shunt was admitted to our
      unit for neurorehabilitation. The patient had a history of anorexia. Her initial
      neurological examination on admission for rehabilitation therapy showed postural
      instability, hemi-hyposthenia, proprioceptive left-sided ataxia, a confusional
      state including temporospatial disorientation, memory disorder and hearing loss.
      Two weeks after the start of her neurorehabilitation program the AFAT program was
      commenced. Pure tone audiometry (PTA) showed lower left hearing thresholds,
      extending from a hearing level (HL) of between 5-25 decibel (dB) or more when
      compared with the right ear. With a rapid and improved regain of unilateral
      hearing loss, balance, cognitive, and motor function also improved. CONCLUSIONS
      This case report supports that patients who undergo rehabilitation following
      stroke, SAH, and hydrocephalus might benefit from a rehabilitation program that
      includes hearing assessment and early improvement of hearing loss, leading to a
      shorter rehabilitation time.

PMID- 30093609
TI  - Holocene reconfiguration and readvance of the East Antarctic Ice Sheet.
AB  - How ice sheets respond to changes in their grounding line is important in
      understanding ice sheet vulnerability to climate and ocean changes. The interplay
      between regional grounding line change and potentially diverse ice flow behaviour
      of contributing catchments is relevant to an ice sheet's stability and resilience
      to change. At the last glacial maximum, marine-based ice streams in the western
      Ross Sea were fed by numerous catchments draining the East Antarctic Ice Sheet.
      Here we present geomorphological and acoustic stratigraphic evidence of ice sheet
      reorganisation in the South Victoria Land (SVL) sector of the western Ross Sea.
      The opening of a grounding line embayment unzipped ice sheet sub-sectors, enabled
      an ice flow direction change and triggered enhanced flow from SVL outlet
      glaciers. These relatively small catchments behaved independently of regional
      grounding line retreat, instead driving an ice sheet readvance that delivered a
      significant volume of ice to the ocean and was sustained for centuries.

PMID- 30093610
TI  - NNMT depletion contributes to liver cancer cell survival by enhancing autophagy
      under nutrient starvation.
AB  - Nicotinamide N-methyl transferase (NNMT) transfers a methyl group from S-adenosyl
      L-methionine (SAM) to nicotinamide (NAM), producing 1-methylnicotinamide (1MNA).
      NNMT has been implicated in several cancer types and recently in metabolism, but
      its role in autophagy regulation has not yet been investigated. In this study, we
      determined that NNMT negatively regulated autophagy at the stage of ULK1
      activation through protein phosphatase 2A (PP2A) activity. Specifically, NNMT
      knockdown increased PP2A methylation and subsequently enhanced phosphatase
      activity. Consequent p-ULK1 (S638) dephosphorylation derepressed ULK1 activity,
      resulting in autophagy induction. Accordingly, NNMT downregulation rescued tumor
      cells under nutrient deficiency in vivo, which was alleviated by ULK1 inhibitor
      treatment. In summary, our results suggest a novel mechanism by which tumor cells
      protect themselves against nutrient deprivation through NNMT suppression to
      accelerate autophagy.

PMID- 30093611
TI  - More replenishment than priming loss of soil organic carbon with additional
      carbon input.
AB  - Increases in carbon (C) inputs to soil can replenish soil organic C (SOC) through
      various mechanisms. However, recent studies have suggested that the increased C
      input can also stimulate the decomposition of old SOC via priming. Whether the
      loss of old SOC by priming can override C replenishment has not been rigorously
      examined. Here we show, through data-model synthesis, that the magnitude of
      replenishment is greater than that of priming, resulting in a net increase in SOC
      by a mean of 32% of the added new C. The magnitude of the net increase in SOC is
      positively correlated with the nitrogen-to-C ratio of the added substrates.
      Additionally, model evaluation indicates that a two-pool interactive model is a
      parsimonious model to represent the SOC decomposition with priming and
      replenishment. Our findings suggest that increasing C input to soils likely
      promote SOC accumulation despite the enhanced decomposition of old C via priming.

PMID- 30093613
TI  - Plant and animal functional diversity drive mutualistic network assembly across
      an elevational gradient.
AB  - Species' functional traits set the blueprint for pair-wise interactions in
      ecological networks. Yet, it is unknown to what extent the functional diversity
      of plant and animal communities controls network assembly along environmental
      gradients in real-world ecosystems. Here we address this question with a unique
      dataset of mutualistic bird-fruit, bird-flower and insect-flower interaction
      networks and associated functional traits of 200 plant and 282 animal species
      sampled along broad climate and land-use gradients on Mt. Kilimanjaro. We show
      that plant functional diversity is mainly limited by precipitation, while animal
      functional diversity is primarily limited by temperature. Furthermore, shifts in
      plant and animal functional diversity along the elevational gradient control the
      niche breadth and partitioning of the respective other trophic level. These
      findings reveal that climatic constraints on the functional diversity of either
      plants or animals determine the relative importance of bottom-up and top-down
      control in plant-animal interaction networks.

PMID- 30093615
TI  - Incubation and water temperatures influence the performances of loggerhead sea
      turtle hatchlings during the dispersal phase.
AB  - Artificial manipulation of incubation temperature has been proposed as a
      potential strategy for mitigating the effects of climate change on sea turtles
      for which sex determination is temperature-dependent, but thermal manipulation
      may also affect hatchling survival. Here, we demonstrated that incubation and
      water temperatures influenced several performance traits that contribute to the
      survival of loggerhead sea turtles (Caretta caretta) during the post-hatchling
      dispersal phase. Hatchlings from warm incubation temperatures (31  degrees C) had
      significantly shorter incubation periods, higher initial swimming performance,
      lower sustained swimming performance, and lower growth rates during the first
      three weeks post-hatching, as well as higher blood glucose concentrations, than
      those from cool incubation temperatures (27.5  degrees C). Hatchlings in warm
      water temperatures (30  degrees C) exhibited significantly greater swimming
      performance than those in cool water temperatures (27  degrees C). Our results
      indicated that altering incubation temperatures indirectly influences the
      survival of loggerhead hatchlings by modifying their swimming performance and
      growth rates, which may affect hatchling predator-avoidance capability. Moreover,
      thermal manipulation may alter the incubation period, exposing hatchling to water
      temperatures that they would not otherwise normally experience, which may affect
      swimming performance. Our results suggest that such conservation strategies may
      influence their survival, and thus should be carefully considered.

PMID- 30093614
TI  - Stationary and portable sequencing-based approaches for tracing wastewater
      contamination in urban stormwater systems.
AB  - Urban sewer systems consist of wastewater and stormwater sewers, of which only
      wastewater is processed before being discharged. Occasionally, misconnections or
      damages in the network occur, resulting in untreated wastewater entering natural
      water bodies via the stormwater system. Cultivation of faecal indicator bacteria
      (e.g. Escherichia coli; E. coli) is the current standard for tracing wastewater
      contamination. This method is cheap but has limited specificity and mobility.
      Here, we compared the E. coli culturing approach with two sequencing-based
      methodologies (Illumina MiSeq 16S rRNA gene amplicon sequencing and Oxford
      Nanopore MinION shotgun metagenomic sequencing), analysing 73 stormwater samples
      collected in Stockholm. High correlations were obtained between E. coli culturing
      counts and frequencies of human gut microbiome amplicon sequences, indicating E.
      coli is indeed a good indicator of faecal contamination. However, the amplicon
      data further holds information on contamination source or alternatively how much
      time has elapsed since the faecal matter has entered the system. Shotgun
      metagenomic sequencing on a subset of the samples using a portable real-time
      sequencer, MinION, correlated well with the amplicon sequencing data. This study
      demonstrates the use of DNA sequencing to detect human faecal contamination in
      stormwater systems and the potential of tracing faecal contamination directly in
      the field.

PMID- 30093616
TI  - Isobenzofuranone derivative JVPH3, an inhibitor of L. donovani topoisomerase II,
      disrupts mitochondrial architecture in trypanosomatid parasites.
AB  - Kinetoplast DNA (kDNA) bearing unusual mitochondrion of trypanosomatid parasites
      offers a new paradigm in chemotherapy modality. Topoisomerase II of Leishmania
      donovani (LdTopII), a key enzyme associated with kDNA replication, is emerging as
      a potential drug target. However, mode of action of LdTopII targeted compounds in
      the parasites at sub-cellular level remains largely unknown. Previously, we
      reported that an isobenzofuranone derivative, namely 3,5-bis(4-chlorophenyl)-7
      hydroxyisobenzofuran-1(3H)-one (JVPH3), targets LdTopII and induces apoptosis
      like cell death in L. donovani. Here, we elucidate the phenotypic changes and the
      events occurring at sub-cellular level caused by JVPH3 in L. donovani. In
      addition, we have evaluated the cytotoxicity and ultrastructural alterations
      caused by JVPH3 in two brazilian trypanosomatid pathogens viz. L. amazonensis and
      Trypanosoma cruzi. Despite killing these parasites, JVPH3 caused significantly
      different phenotypes in L. donovani and L. amazonensis. More than 90% population
      of parasites showed altered morphology. Mitochondrion was a major target
      organelle subsequently causing kinetoplast network disorganization in Leishmania.
      Altered mitochondrial architecture was evident in 75-80% Leishmania population
      being investigated. Quantification of mitochondrial function using JC-1
      fluorophore to measure a possible mitochondrial membrane depolarization further
      confirmed the mitochondrion as an essential target of the JVPH3 corroborating
      with the phenotype observed by electron microscopy. However, the impact of JVPH3
      was lesser on T. cruzi than Leishmania. The molecule caused mitochondrial
      alteration in 40% population of the epimastigotes being investigated. To our
      knowledge, this is the first report to evaluate the proliferation pattern and
      ultrastructural alterations caused in Brazilian kinetoplastid pathogens by a
      synthetic LdTopII inhibitor previously established to have promising in vivo
      activity against Indian strain of L. donovani.

PMID- 30093617
TI  - Use and perceived safety of stylets for neonatal endotracheal intubation: a
      national survey.
AB  - OBJECTIVE: To examine the use and perceived safety of stylets for neonatal
      intubation in a cohort of providers in the United States. STUDY DESIGN: A cross
      sectional survey was sent to members of the American Academy of Pediatrics
      Section on Neonatal-Perinatal Medicine. RESULT: A total of 640 responses were
      received. 57% reported using a stylet 'every time' or 'almost every time' they
      intubated. The preferred stylet bend was a smooth bend of <30 degrees. 71% of
      respondents believed that stylets were safe. Reported complications from stylet
      use included tube dislodgement during stylet removal (32%), airway injury with
      bleeding (9%), and tracheal perforation (2%). CONCLUSION: Stylet use was common.
      There was fair consistency on preference for stylet bend and position. Stylet use
      was believed to be safe, but complications were observed by many respondents.
      Additional studies are needed to examine the risks and benefits of stylet use
      during neonatal intubation.

PMID- 30093618
TI  - Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and
      predictive ability.
AB  - OBJECTIVE: To test the non-inferiority of an alternative to the Apgar score.
      STUDY DESIGN: The Neonatal Resuscitation and Adaptation Score (NRAS) was recorded
      in parallel to the Apgar score by a resuscitation team at deliveries. Correlation
      between the systems was assessed, as well as the predictive ability of NRAS and
      Apgar scores for mortality or short-term morbidities. RESULTS: A total of 340
      infants were in the study group. The two scores correlated strongly (r = 0.87 and
      0.83 at 1 and 5 min, respectively). Those needing ventilation at 48 h of life had
      a 5-min NRAS < 7 in 23/26 vs Apgar < 7 (23/36, p = 0.001). A low (0-3) 1-min NRAS
      score was more predictive of death, 53% vs 17%, p = 0.0065. CONCLUSIONS: NRAS
      correlates with Apgar status assessment, and identifies newborns who die or may
      require further care better than the Apgar score.

PMID- 30093620
TI  - Reply to 'C-C bond cleavage in biosynthesis of 4-alkyl-L-proline precursors of
      lincomycin and anthramycin cannot precede C-methylation'.

PMID- 30093619
TI  - Structural basis for reactivating the mutant TERT promoter by cooperative binding
      of p52 and ETS1.
AB  - Transcriptional factors ETS1/2 and p52 synergize downstream of non-canonical NF
      kappaB signaling to drive reactivation of the -146C>T mutant TERT promoter in
      multiple cancer types, but the mechanism underlying this cooperativity remains
      unknown. Here we report the crystal structure of a ternary p52/ETS1/-146C>T TERT
      promoter complex. While p52 needs to associate with consensus kappaB sites on the
      DNA to function during non-canonical NF-kappaB signaling, we show that p52 can
      activate the -146C>T TERT promoter without binding DNA. Instead, p52 interacts
      with ETS1 to form a heterotetramer, counteracting autoinhibition of ETS1.
      Analogous to observations with the GABPA/GABPB heterotetramer, the native
      flanking ETS motifs are required for sustained activation of the -146C>T TERT
      promoter by the p52/ETS1 heterotetramer. These observations provide a unifying
      mechanism for transcriptional activation by GABP and ETS1, and suggest that
      genome-wide targets of non-canonical NF-kappaB signaling are not limited to those
      driven by consensus kappaB sequences.

PMID- 30093612
TI  - Identification of nine new susceptibility loci for endometrial cancer.
AB  - Endometrial cancer is the most commonly diagnosed cancer of the female
      reproductive tract in developed countries. Through genome-wide association
      studies (GWAS), we have previously identified eight risk loci for endometrial
      cancer. Here, we present an expanded meta-analysis of 12,906 endometrial cancer
      cases and 108,979 controls (including new genotype data for 5624 cases) and
      identify nine novel genome-wide significant loci, including a locus on 12q24.12
      previously identified by meta-GWAS of endometrial and colorectal cancer. At five
      loci, expression quantitative trait locus (eQTL) analyses identify candidate
      causal genes; risk alleles at two of these loci associate with decreased
      expression of genes, which encode negative regulators of oncogenic signal
      transduction proteins (SH2B3 (12q24.12) and NF1 (17q11.2)). In summary, this
      study has doubled the number of known endometrial cancer risk loci and revealed
      candidate causal genes for future study.

PMID- 30093621
TI  - Suboptimal Coding Metasurfaces for Terahertz Diffuse Scattering.
AB  - Coding metasurfaces, composed of only two types of elements arranged according to
      a binary code, are attracting a steadily increasing interest in many application
      scenarios. In this study, we apply this concept to attain diffuse scattering at
      THz frequencies. Building up on previously derived theoretical results, we carry
      out a suboptimal metasurface design based on a simple, deterministic and
      computationally inexpensive algorithm that can be applied to arbitrarily large
      structures. For experimental validation, we fabricate and characterize three
      prototypes working at 1 THz, which, in accordance with numerical predictions,
      exhibit significant reductions of the radar cross-section, with reasonably good
      frequency and angular stability. Besides the radar-signature control, our results
      may also find potentially interesting applications to diffusive imaging,
      computational imaging, and (scaled to optical wavelengths) photovoltaics.

PMID- 30093622
TI  - Soil microarthropods alter the outcome of plant-soil feedback experiments.
AB  - Plant-soil feedback (PSF) effects are studied as plant growth responses to soil
      previously conditioned by another plant. These studies usually exclude effects of
      soil fauna, such as nematodes, soil arthropods, and earthworms, although these
      organisms are known to influence plant performance. Here, we aimed to explore
      effects of a model microarthropod community on PSFs. We performed a PSF
      experiment in microcosms with two plant species, Phleum pratense and Poa
      pratensis. We added a model microarthropod community consisting of three
      fungivorous springtail species (Proisotoma minuta, Folsomia candida, and Sinella
      curviseta) and a predatory mite (Hypoaspis aculeifer) to half of the microcosms.
      We measured seedling establishment and plant biomass, nematode and microbial
      community composition, microbial biomass, and mycorrhizal colonization of roots.
      Microarthropods caused changes in the composition of nematode and microbial
      communities. Their effect was particularly strong in Phleum plants where they
      altered the composition of bacterial communities. Microarthropods also generally
      influenced plant performance, and their effects depended on previous soil
      conditioning and the identity of plant species. Microarthropods did not affect
      soil microbial biomass and mycorrhizal colonization of roots. We conclude that
      the role of soil microarthropods should be considered in future PSF experiments,
      especially as their effects are plant species-specific.

PMID- 30093623
TI  - Short and Long-Term Potential Role of Carbon Nanoparticles in Total Thyroidectomy
      with Central Lymph Node Dissection.
AB  - Whether we should use carbon nanoparticle (CN) routinely in thyroid surgery is
      still controversial. 406 papillary thyroid cancer (PTC) patients who underwent
      total thyroidectomy (TT) with bilateral central lymph node dissection (CLND) from
      January 2010 to December 2012 were retrospectively analyzed. The incidence of
      transient hypoparathyroidism and hypocalcemia in CN group was significantly lower
      than the control group at second, fifth day after surgery (P = 0.004, 0.042,
      0.002 and 0.045 respectively). However, no significant difference existed between
      the two groups about the permanent hypoparathyroidism and hypocalcemia (P =
      1.000). Total number of central lymph nodes and metastatic lymph nodes in CN
      group were more than those in control group (P = 0.031 and 0.038 respectively).
      However, recurrence was not significantly different between the two groups after
      at least 5-year follow up (P = 0.7917). In the subgroup of prophylactic and
      therapeutic CLND study, no significant difference existed between the two groups
      (P = 0.5295 and 0.8459 respectively). CN significantly help in identifying the
      parathyroid glands in surgery and increased the number of lymph nodes in central
      compartment. However, we should not exaggerate the function of CN since it
      couldn't improve the permanent hypoparathyroidism and recurrence in PTC patients
      who underwent TT with bilateral CLND.

PMID- 30093625
TI  - Riverbed erosion of the final 565 kilometers of the Yangtze River (Changjiang)
      following construction of the Three Gorges Dam.
AB  - The world's largest hydropower dam, the Three Gorges Dam (TGD), spans the upper
      Yangtze River in China, creating a 660-km long and 1.1-km wide reservoir
      upstream. Several recent studies reported a considerable decline in sediment load
      of the Lowermost Yangtze River (LmYR) and a rapid erosion in the subaqueous delta
      of the river mouth after the closure of the TGD in 2003. However, it is unknown
      if the TGD construction has also affected river channel and bed formation of the
      LmYR. In this study, we compared bathymetric data of the last 565 kilometers of
      the Yangtze River's channel between 1998 and 2013. We found severe channel
      erosion following the TGD closure, with local riverbed erosion up to 10 m deep.
      The total volume of net erosion from the 565-km channel amounted to 1.85 billion
      m3, an equivalent of 2.59 billion metric tons of sediment, assuming a bulk
      density of 1.4 t/m3 for the riverbed material. The largest erosion occurred in a
      100-km reach close to the Yangtze River mouth, contributing up to 73% of the
      total net eroded channel volume.

PMID- 30093626
TI  - BCG enriches Treg cells.

PMID- 30093624
TI  - Assessment of in vivo versus in vitro biofilm formation of clinical methicillin
      resistant Staphylococcus aureus isolates from endotracheal tubes.
AB  - Our aim was to demonstrate that biofilm formation in a clinical strain of
      methicillin-resistant Staphylococcus aureus (MRSA) can be enhanced by environment
      exposure in an endotracheal tube (ETT) and to determine how it is affected by
      systemic treatment and atmospheric conditions. Second, we aimed to assess biofilm
      production dynamics after extubation. We prospectively analyzed 70 ETT samples
      obtained from pigs randomized to be untreated (controls, n = 20), or treated with
      vancomycin (n = 32) or linezolid (n = 18). A clinical MRSA strain (MRSA-in) was
      inoculated in pigs to create a pneumonia model, before treating with antibiotics.
      Tracheally intubated pigs with MRSA severe pneumonia, were mechanically
      ventilated for 69 +/- 16 hours. All MRSA isolates retrieved from ETTs (ETT-MRSA)
      were tested for their in vitro biofilm production by microtiter plate assay. In
      vitro biofilm production of MRSA isolates was sequentially studied over the next
      8 days post-extubation to assess biofilm capability dynamics over time. All
      experiments were performed under ambient air (O2) or ambient air supplemented
      with 5% CO2. We collected 52 ETT-MRSA isolates (placebo N = 19, linezolid N = 11,
      and vancomycin N = 22) that were clonally identical to the MRSA-in. Among the ETT
      MRSA isolates, biofilm production more than doubled after extubation in 40% and
      50% under 5% CO2 and O2, respectively. Systemic antibiotic treatment during
      intubation did not affect this outcome. Under both atmospheric conditions,
      biofilm production for MRSA-in was at least doubled for 9 ETT-MRSA isolates, and
      assessment of these showed that biofilm production decreased progressively over a
      4-day period after extubation. In conclusion, a weak biofilm producer MRSA strain
      significantly enhances its biofilm production within an ETT, but it is influenced
      by the ETT environment rather than by the systemic treatment used during
      intubation or by the atmospheric conditions used for bacterial growth.

PMID- 30093627
TI  - Omega-3 fatty acids are a potential therapy for patients with sickle cell
      disease.

PMID- 30093628
TI  - Transcriptomic analysis of CIC and ATXN1L reveal a functional relationship
      exploited by cancer.
AB  - Aberrations in Capicua (CIC) have recently been implicated as a negative
      prognostic factor in a multitude of cancer types through activation of the MAPK
      signalling cascade and derepression of oncogenic ETS transcription factors. The
      Ataxin-family protein ATXN1L has previously been reported to interact with CIC in
      developmental and disease contexts to facilitate the repression of CIC target
      genes. To further investigate this relationship, we performed functional in vitro
      studies utilizing ATXN1LKO and CICKO human cell lines and characterized a
      reciprocal functional relationship between CIC and ATXN1L. Transcriptomic
      interrogation of the CIC-ATXN1-ATXN1L axis in low-grade glioma, prostate
      adenocarcinoma and stomach adenocarcinoma TCGA cohorts revealed context-dependent
      convergence of gene sets and pathways related to mitotic cell cycle and division.
      This study highlights the CIC-ATXN1-ATXN1L axis as a more potent regulator of the
      cell cycle than previously appreciated.

PMID- 30093629
TI  - SIRT7 promotes thyroid tumorigenesis through phosphorylation and activation of
      Akt and p70S6K1 via DBC1/SIRT1 axis.
AB  - SIRT7 is an NAD+-dependent histone/non-histone deacetylase, which is highly
      expressed in different types of cancer including thyroid cancer; however, its
      biological function in thyroid cancer is still undiscovered. In this study, we
      found that SIRT7 expression was elevated in papillary thyroid cancers (PTCs), and
      demonstrated that SIRT7 knockdown dramatically inhibited the proliferation,
      colony formation, migration and invasion of thyroid cancer cells, and induced
      thyroid cancer cell cycle arrest and apoptosis. Conversely, SIRT7 re-expression
      markedly enhanced thyroid cancer cell growth, invasiveness and tumorigenic
      potential in nude mice. Further studies revealed that SIRT7 exerted an oncogenic
      function in thyroid tumorigenesis by phosphorylation of Akt and p70S6K1.
      Mechanistically, SIRT7 binds to the promoter of deleted in breast cancer-1
      (DBC1), an endogenous inhibitor of SIRT1, and represses its transcription via
      deacetylation of H3K18Ac. This results in enhanced interactions between SIRT1 and
      Akt or p70S6K1, thereby promoting deacetylation and subsequent phosphorylation of
      Akt and p70S6K1 through a SIRT1-dependent manner. Altogether, our results show
      that DBC1 is a downstream target of SIRT7, and first uncover that SIRT7 promotes
      thyroid tumorigenesis through phosphorylation and activation of Akt and p70S6K1
      via the modulation of DBC1/SIRT1 axis.

PMID- 30093630
TI  - Acquired SETD2 mutation and impaired CREB1 activation confer cisplatin resistance
      in metastatic non-small cell lung cancer.
AB  - Resistance to chemotherapy remains a critical barrier to effective cancer
      treatment. Although cisplatin is one of the most commonly used chemotherapeutic
      agents in the treatment of non-small cell lung cancer (NSCLC), mechanisms of
      resistance to this drug are not fully understood. Here, we report a novel
      cisplatin-resistance mechanism involving SET Domain Containing 2 (SETD2), a
      histone H3 lysine 36 (H3K36) trimethyltransferase, and cAMP-responsive element
      binding protein 1 (CREB1). A549 cells selected in vivo to give brain metastases
      exhibited cisplatin resistance and decreased expression of phosphorylated CREB1.
      Next-generation sequencing (NGS) analysis identified a missense mutation in SETD2
      (p.T1171K), and we demonstrated that SETD2-mediated trimethylation of H3K36
      (H3K36me3) and CREB1 phosphorylation are critical for cellular sensitivity to
      cisplatin. Moreover, we showed that suppression of SETD2 or CREB1 and ectopic
      expression of mutant SETD2 conferred cisplatin resistance through inhibition of
      H3K36me3 and ERK activation in NSCLC cells. Our results provide evidence that
      SETD2 and CREB1 contribute to cisplatin cytotoxicity via regulation of the ERK
      signaling pathway, and their inactivation may lead to cisplatin resistance.

PMID- 30093631
TI  - Compatibility of RUNX1/ETO fusion protein modules driving CD34+ human progenitor
      cell expansion.
AB  - Chromosomal translocations represent frequent events in leukemia. In t(8;21)+
      acute myeloid leukemia, RUNX1 is fused to nearly the entire ETO protein, which
      contains four conserved nervy homology regions, NHR1-4. Furthermore RUNX1/ETO
      interacts with ETO-homologous proteins via NHR2, thereby multiplying NHR domain
      contacts. As shown recently, RUNX1/ETO retains oncogenic activity upon either
      deletion of the NHR3 + 4 N-CoR/SMRT interaction domain or substitution of the
      NHR2 tetramer domain. Thus, we aimed to clarify the specificities of the NHR
      domains. A C-terminally NHR3 + 4 truncated RUNX1/ETO containing a heterologous,
      structurally highly related non-NHR2 tetramer interface translocated into the
      nucleus and bound to RUNX1 consensus motifs. However, it failed to interact with
      ETO-homologues, repress RUNX1 targets, and transform progenitors. Surprisingly,
      transforming capacity was fully restored by C-terminal fusion with ETO's NHR4
      zinc-finger or the repressor domain 3 of N-CoR, while other repression domains
      failed. With an inducible protein assembly system, we further demonstrated that
      NHR4 domain activity is critically required early in the establishment of
      progenitor cultures expressing the NHR2 exchanged truncated RUNX1/ETO. Together,
      we can show that NHR2 and NHR4 domains can be replaced by heterologous protein
      domains conferring tetramerization and repressor functions, thus showing that the
      NHR2 and NHR4 domain structures do not have irreplaceable functions concerning
      RUNX1/ETO activity for the establishment of human CD34+ cell expansion. We could
      resemble the function of RUNX1/ETO through modular recomposition with protein
      domains from RUNX1, ETO, BCR and N-CoR without any NHR2 and NHR4 sequences. As
      most transcriptional repressor proteins do not comprise tetramerization domains,
      our results provide a possible explanation as to the reason that RUNX1 is
      recurrently found translocated to ETO family members, which all contain tetramer
      together with transcriptional repressor moieties.

PMID- 30093632
TI  - O-GlcNAcylation promotes colorectal cancer metastasis via the miR-101-O
      GlcNAc/EZH2 regulatory feedback circuit.
AB  - Advanced colorectal cancer (CRC) is one of the deadliest cancers, and the 5-year
      survival rate of patients with metastasis is extremely low. The epithelial
      mesenchymal transition (EMT) is considered essential for metastatic CRC, but the
      fundamental molecular basis underlying this effect remains unknown. Here, we
      identified that O-GlcNAcylation, a unique posttranslational modification (PTM)
      involved in cancer metabolic reprogramming, increased the metastatic capability
      of CRC. The levels of O-GlcNAcylation were increased in the metastatic CRC
      tissues and cell lines, which likely promoted the EMT by enhancing EZH2 protein
      stability and function. The CRC patients with higher levels of O-GlcNAcylation
      exhibited greater lymph node metastasis potential and lower overall survival.
      Bioinformatic analysis and luciferase reporter assays revealed that both O
      GlcNAcylation transferase (OGT) and EZH2 are posttranscriptionally inhibited by
      microRNA-101. In addition, O-GlcNAcylation and H3K27me3 modification in the miR
      101 promoter region further inhibited the transcription of miR-101, resulting in
      the upregulation of OGT and EZH2 in metastatic CRC, thus forming a vicious cycle.
      In this study, we demonstrated that O-GlcNAcylation, which is negatively
      regulated by microRNA-101, likely promotes CRC metastasis by enhancing EZH2
      protein stability and function. Reducing O-GlcNAcylation may be a potential
      therapeutic strategy for metastatic CRC.

PMID- 30093633
TI  - Cross-species genomics identifies DLG2 as a tumor suppressor in osteosarcoma.
AB  - Leveraging the conserved cancer genomes across mammals has the potential to
      transform driver gene discovery in orphan cancers. Here, we combine cross-species
      genomics with validation across human-dog-mouse systems to uncover a new bone
      tumor suppressor gene. Comparative genomics of spontaneous human and dog
      osteosarcomas (OS) expose Disks Large Homolog 2 (DLG2) as a tumor suppressor
      candidate. DLG2 copy number loss occurs in 42% of human and 56% of canine OS.
      Functional validation through pertinent human and canine OS DLG2-deficient cell
      lines identifies a regulatory role of DLG2 in cell division, migration and
      tumorigenesis. Moreover, osteoblast-specific deletion of Dlg2 in a clinically
      relevant genetically engineered mouse model leads to acceleration of OS
      development, establishing DLG2 as a critical determinant of OS. This widely
      applicable cross-species approach serves as a platform to expedite the search of
      cancer drivers in rare human malignancies, offering new targets for cancer
      therapy.

PMID- 30093635
TI  - Profile distribution of CO2 in an arid saline-alkali soil with gypsum and wheat
      straw amendments: a two-year incubation experiment.
AB  - Adding gypsum and/or straw is a common practice for ameliorating saline-alkali
      soils. However, the effect of amendment on soil CO2 is poorly known. An
      incubation experiment was conducted for over two years in a saline-alkali soil of
      Yanqi Basin, which included four treatments: control, gypsum addition (Ca), wheat
      straw addition (S) and gypsum-wheat straw combination (Ca+S). We continuously
      monitored soil CO2 concentration, temperature and moisture at 15, 30, 45 and 60
      cm. There was a clear seasonality in soil CO2 under all four treatments, which
      was generally similar to those in soil temperature and moisture. Straw addition
      led to a significant increase in soil CO2 over 0-60 cm in summer. While there was
      a significant increase of soil CO2 with gypsum addition only, soil CO2
      significantly decreased with the addition of gypsum and straw (relative to straw
      addition only) during autumn and winter in 2014. Interestingly, integrated soil
      CO2 was lowest in soil profile under the Ca+S treatment during winter and spring.
      Our study implies that different amendments of organic matter and gypsum may
      result in various responses and interactions of biological, chemical and physical
      processes, with implications for the carbon cycle in saline-alkaline soils of
      arid region.

PMID- 30093634
TI  - Dual role for miR-34a in the control of early progenitor proliferation and
      commitment in the mammary gland and in breast cancer.
AB  - The role of the tumour-suppressor miR-34 family in breast physiology and in
      mammary stem cells (MaSCs) is largely unknown. Here, we revealed that miR-34
      family, and miR-34a in particular, is implicated in mammary epithelium
      homoeostasis. Expression of miR-34a occurs upon luminal commitment and
      differentiation and serves to inhibit the expansion of the pool of MaSCs and
      early progenitor cells, likely in a p53-independent fashion. Mutant mice (miR34
      KO) and loss-of-function approaches revealed two separate functions of miR-34a,
      controlling both proliferation and fate commitment in mammary progenitors by
      modulating several pathways involved in epithelial cell plasticity and luminal-to
      basal conversion. In particular, miR-34a acts as endogenous inhibitor of the
      Wnt/beta-catenin signalling pathway, targeting up to nine upstream regulators at
      the same time, thus modulating the expansion of the MaSCs/early progenitor pool.
      These multiple roles of miR-34a are maintained in a model of human breast cancer,
      in which chronic expression of miR-34a in triple-negative mesenchymal-like cells
      (enriched in cancer stem cells-CSCs) could promote a luminal-like differentiation
      programme, restrict the CSC pool, and inhibit tumour propagation. Hence,
      activation of miR-34a-dependent programmes could provide a therapeutic
      opportunity for the subset of breast cancers, which are rich in CSCs and respond
      poorly to conventional therapies.

PMID- 30093636
TI  - Synchronous multi-color laser network with daily sub-femtosecond timing drift.
AB  - Filming atoms in motion with sub-atomic spatiotemporal resolution is one of the
      distinguished scientific endeavors of our time. Newly emerging X-ray laser
      facilities are the most likely candidates to enable such a detailed gazing of
      atoms due to their angstrom-level radiation wavelength. To provide the necessary
      temporal resolution, numerous mode-locked lasers must be synchronized with ultra
      high precision across kilometer-distances. Here, we demonstrate a metronome
      synchronizing a network of pulsed-lasers operating at different center
      wavelengths and different repetition rates over 4.7-km distance. The network
      achieves a record-low timing drift of 0.6 fs RMS measured with 2-Hz sampling over
      40 h. Short-term stability measurements show an out-of-loop timing jitter of only
      1.3 fs RMS integrated from 1 Hz to 1 MHz. To validate the network performance, we
      present a comprehensive noise analysis based on the feedback flow between the
      setup elements. Our analysis identifies nine uncorrelated noise sources, out of
      which the slave laser's inherent jitter dominates with 1.26 fs RMS. This suggests
      that the timing precision of the network is not limited by the synchronization
      technique, and so could be much further improved by developing lasers with lower
      inherent noise.

PMID- 30093637
TI  - Feasibility of autologous plasma gel for tonsil-derived stem cell therapeutics in
      hypoparathyroidism.
AB  - Hypoparathyroidism is a deficiency of the parathyroid hormone (PTH) in the body.
      We previously reported the possibility of treating it using tonsil-derived
      mesenchymal stem cells (TMSCs) differentiated into PTH-releasing cells. The
      purpose of this study was to evaluate the feasibility of using autologous plasma
      gel as scaffold material in treatment of hypoparathyroidism with TMSC. We
      obtained plasma by venous sampling of autologous blood and centrifuged and
      fabricated the plasma gel using a sinusoidal pattern heating machine. After we
      created the hypoparathyroidism animal model, we administered undifferentiated
      TMSCs and TMSCs differentiated into parathyroid cells at each rat dorsum by
      intramuscular injection with and without the plasma gel. In the plasma gel
      groups, intact PTH was detected from on day 21 after TMSC injection; we did not
      detect intact PTH in the groups that were only transplanted with TMSCs during the
      entire experimental period. Serum calcium was higher and phosphorous was lower in
      the TMSC with plasma gel groups than in the groups with TMSCs alone. We detected
      PTH and chromogranin A in the TMSC-plasma gel-transplanted areas on
      immunohistochemistry and immunofluorescence stain. Plasma gel can be considered
      as a cell-delivery scaffold for treating hypoparathyroidism with tonsil-derived
      mesenchymal stem cells.

PMID- 30093640
TI  - Post-drought decline of the Amazon carbon sink.
AB  - Amazon forests have experienced frequent and severe droughts in the past two
      decades. However, little is known about the large-scale legacy of droughts on
      carbon stocks and dynamics of forests. Using systematic sampling of forest
      structure measured by LiDAR waveforms from 2003 to 2008, here we show a
      significant loss of carbon over the entire Amazon basin at a rate of 0.3 +/- 0.2
      (95% CI) PgC yr-1 after the 2005 mega-drought, which continued persistently over
      the next 3 years (2005-2008). The changes in forest structure, captured by
      average LiDAR forest height and converted to above ground biomass carbon density,
      show an average loss of 2.35 +/- 1.80 MgC ha-1 a year after (2006) in the
      epicenter of the drought. With more frequent droughts expected in future, forests
      of Amazon may lose their role as a robust sink of carbon, leading to a
      significant positive climate feedback and exacerbating warming trends.

PMID- 30093638
TI  - High-resolution visualization of H3 variants during replication reveals their
      controlled recycling.
AB  - DNA replication is a challenge for the faithful transmission of parental
      information to daughter cells, as both DNA and chromatin organization must be
      duplicated. Replication stress further complicates the safeguard of epigenome
      integrity. Here, we investigate the transmission of the histone variants H3.3 and
      H3.1 during replication. We follow their distribution relative to replication
      timing, first in the genome and, second, in 3D using super-resolution microscopy.
      We find that H3.3 and H3.1 mark early- and late-replicating chromatin,
      respectively. In the nucleus, H3.3 forms domains, which decrease in density
      throughout replication, while H3.1 domains increase in density. Hydroxyurea
      impairs local recycling of parental histones at replication sites. Similarly,
      depleting the histone chaperone ASF1 affects recycling, leading to an impaired
      histone variant landscape. We discuss how faithful transmission of histone
      variants involves ASF1 and can be impacted by replication stress, with ensuing
      consequences for cell fate and tumorigenesis.

PMID- 30093641
TI  - Single-shot condensation of exciton polaritons and the hole burning effect.
AB  - A bosonic condensate of exciton polaritons in a semiconductor microcavity is a
      macroscopic quantum state subject to pumping and decay. The fundamental nature of
      this driven-dissipative condensate is still under debate. Here, we gain an
      insight into spontaneous condensation by imaging long-lifetime exciton polaritons
      in a high-quality inorganic microcavity in a single-shot optical excitation
      regime, without averaging over multiple condensate realisations. We demonstrate
      that condensation is strongly influenced by an incoherent reservoir and that the
      reservoir depletion, the so-called spatial hole burning, is critical for the
      transition to the ground state. Condensates of photon-like polaritons exhibit
      strong shot-to-shot fluctuations and density filamentation due to the effective
      self-focusing associated with the reservoir depletion. In contrast, condensates
      of exciton-like polaritons display smoother spatial density distributions and are
      second-order coherent. Our observations show that the single-shot measurements
      offer a unique opportunity to study fundamental properties of non-equilibrium
      condensation in the presence of a reservoir.

PMID- 30093639
TI  - Genome-wide association study identifies multiple new loci associated with Ewing
      sarcoma susceptibility.
AB  - Ewing sarcoma (EWS) is a pediatric cancer characterized by the EWSR1-FLI1 fusion.
      We performed a genome-wide association study of 733 EWS cases and 1346 unaffected
      individuals of European ancestry. Our study replicates previously reported
      susceptibility loci at 1p36.22, 10q21.3 and 15q15.1, and identifies new loci at
      6p25.1, 20p11.22 and 20p11.23. Effect estimates exhibit odds ratios in excess of
      1.7, which is high for cancer GWAS, and striking in light of the rarity of EWS
      cases in familial cancer syndromes. Expression quantitative trait locus (eQTL)
      analyses identify candidate genes at 6p25.1 (RREB1) and 20p11.23 (KIZ). The
      20p11.22 locus is near NKX2-2, a highly overexpressed gene in EWS. Interestingly,
      most loci reside near GGAA repeat sequences and may disrupt binding of the EWSR1
      FLI1 fusion protein. The high locus to case discovery ratio from 733 EWS cases
      suggests a genetic architecture in which moderate risk SNPs constitute a
      significant fraction of risk.

PMID- 30093642
TI  - C-C bond cleavage in biosynthesis of 4-alkyl-L-proline precursors of lincomycin
      and anthramycin cannot precede C-methylation.

PMID- 30093644
TI  - The Role of Nano-domains in {1-011} Twinned Martensite in Metastable Titanium
      Alloys.
AB  - The formation mechanism of [Formula: see text] type twinned alpha'-martensitic
      structures was investigated in titanium alloys, and in-depth characterizations of
      the microstructures were performed using scanning electron microscopy and
      transmission electron microscopy. The randomly distributed nano-domains nucleated
      by water quenching were sheared during the primary martensite transformation.
      Experimental results revealed that this sheared nano-domain interferes with the
      primary martensite transformation and induces a secondary martensite
      transformation. In terms of crystallography, the secondary martensite transformed
      from the sheared nano-domain has a [Formula: see text] type twin relationship
      with the primary martensite. The growth of both martensites yielded a more
      twinned martensitic structure as the applied strain increased.

PMID- 30093647
TI  - Thick Film Ni0.5Mn0.5-xSnx Heusler Alloys by Multi-layer Electrochemical
      Deposition.
AB  - The design of multifunctional alloys with multiple chemical components requires
      controllable synthesis approaches. Physical vapor deposition techniques, which
      result in thin films (<1 MUm), have previously been demonstrated for
      micromechanical devices and metallic combinatorial libraries. However, this
      approach deviates from bulk-like properties due to the residual stress derived in
      thin films and is limited by total film thickness. Here, we report a route to
      obtain ternary Ni-Mn-Sn alloy thick films with controllable compositions and
      thicknesses by annealing electrochemically deposited multi-layer monatomic (Ni,
      Mn, Sn) films, deposited sequentially from separate aqueous deposition baths. We
      demonstrate (1) controllable compositions, with high degree of uniformity, (2)
      smooth films, and (3) high reproducibility between film transformation behavior.
      Our results demonstrate a positive correlation between alloy film thicknesses and
      grain sizes, as well as consistent bulk-like transformation behavior.

PMID- 30093645
TI  - A cis-eQTL of HLA-DPB1 Affects Susceptibility to Type 1 Autoimmune Hepatitis.
AB  - Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease characterized
      by an autoimmune reaction to hepatocytes. A single nucleotide polymorphism in the
      3' untranslated region of HLA-DPB1, rs9277534, is associated with HLA-DPB1
      expression. rs9277534 has been linked to hepatitis B virus recovery/persistence
      and the risk of graft-versus-host disease with HLA-DPB1 mismatching
      transplantation of hematopoietic cells, but its role along with that of HLA-DP
      expression in AIH have not been fully clarified. We genotyped rs9277534 in 146
      Japanese patients with AIH and 326 healthy subjects. HLA-DPB1 expression was
      determined by quantitative PCR. HLA-DPB1 expression was significantly higher for
      rs9277534G than for rs9277534A (P < 0.05). rs9277534 genotype was in strong
      linkage disequilibrium with the HLA-DPB1 allele (pairwise D' = 0.82-1.00).
      Although HLA-DP alleles were not significantly associated with AIH, the frequency
      of the rs9277534G allele was significantly higher in AIH patients compared with
      healthy subjects (P = 0.002, odds ratio [OR] = 1.56). Logistic regression
      analysis revealed that the HLA-DRB1*04:05 allele (P < 0.001, OR = 4.61) and
      rs9277534 (P = 0.004, OR = 1.67) were independently associated with AIH
      susceptibility. rs9277534G in the HLA-DP gene is an eQTL that affects gene
      expression and may contribute to AIH susceptibility.

PMID- 30093646
TI  - A Late Cretaceous amber biota from central Myanmar.
AB  - Insect faunas are extremely rare near the latest Cretaceous with a 24-million
      year gap spanning from the early Campanian to the early Eocene. Here, we report a
      unique amber biota from the Upper Cretaceous (uppermost Campanian ~72.1 Ma) of
      Tilin, central Myanmar. The chemical composition of Tilin amber suggests a tree
      source among conifers, indicating that gymnosperms were still abundant in the
      latest Campanian equatorial forests. Eight orders and 12 families of insects have
      been found in Tilin amber so far, making it the latest known diverse insect
      assemblage in the Mesozoic. The presence of ants of the extant subfamilies
      Dolichoderinae and Ponerinae supports that tropical forests were the cradle for
      the diversification of crown-group ants, and suggests that the turnover from stem
      groups to crown groups had already begun at ~72.1 Ma. Tilin amber biota fills a
      critical insect faunal gap and provides a rare insight into the latest Campanian
      forest ecosystem.

PMID- 30093648
TI  - Tetrahedral honeycomb surface reconstructions of quartz, cristobalite and
      stishovite.
AB  - Crystalline silica (SiO2) is a major material used in many technologies, yet the
      exact surface structures of silica polymorphs are still mostly unknown. Here we
      perform a comprehensive study of surface reconstructions of alpha-cristobalite
      (001), alpha-quartz (001) and stishovite (110) and (100) using evolutionary
      algorithm USPEX in conjunction with ab initio calculations. We found the well
      known "dense surface" to be among low-energy reconstructions of alpha-quartz
      (001), as well as its previously proposed distorted version, which we call
      "shifted surface". For cristobalite and stishovite we show the formation of
      reconstructions without dangling bonds which share common features with well
      known "dense surface" of alpha-quartz (001). We call them "dense cristobalite"
      and "dense stishovite" - all of these have honeycomb arrangements of corner
      sharing SiO4-tetrahedra in the surface layers. These tetrahedral honeycombs have
      very low surface energies, and such tetrahedral surface pattern is observed even
      in stishovite (the bulk structure of which has SiO6-octahedra, rather than SiO4
      tetrahedra).

PMID- 30093650
TI  - Author Correction: Metabolomics profiling reveals differential adaptation of
      major energy metabolism pathways associated with autophagy upon oxygen and
      glucose reduction.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30093649
TI  - Topical administration of EGF suppresses immune response and protects skin
      barrier in DNCB-induced atopic dermatitis in NC/Nga mice.
AB  - Atopic dermatitis (AD) is a common inflammatory skin disease characterized by a
      complex, heterogeneous pathogenesis including skin barrier dysfunction,
      immunology, and pruritus. Although epidermal growth factor (EGF) is essential for
      epithelial homeostasis and wound healing, the effect of EGF on AD remains to be
      explored. To develop a new therapy for AD, the anti-AD potential of EGF was
      investigated by inducing AD-like skin lesions in NC/Nga mice using 2,4
      dinitrochlorobenzene (DNCB). EGF was administrated to NC/Nga mice to evaluate its
      therapeutic effect on DNCB-induced AD. EGF treatment improved dermatitis score,
      ear thickness, epidermal hyperplasia, serum total immunoglobulin E level, and
      transepidermal water loss in NC/Nga mice with DNCB-induced AD. In addition,
      levels of skin barrier-related proteins such as filaggrin, involucrin, loricrin,
      occludin, and zonula occludens-1 (ZO-1) were increased by EGF treatment. These
      beneficial effects of EGF on AD may be mediated by EGF regulation of Th1/Th2
      mediated cytokines, mast cell hyperplasia, and protease activated receptor-2 (PAR
      2) and thymic stromal lymphopoietin (TSLP), which are triggers of AD. Taken
      together, our findings suggest that EGF may potentially protect against AD
      lesional skin via regulation of skin barrier function and immune response.

PMID- 30093643
TI  - Gene therapy for neurological disorders: progress and prospects.
AB  - Adeno-associated viral (AAV) vectors are a rapidly emerging gene therapy platform
      for the treatment of neurological diseases. In preclinical studies, transgenes
      encoding therapeutic proteins, microRNAs, antibodies or gene-editing machinery
      have been successfully delivered to the central nervous system with natural or
      engineered viral capsids via various routes of administration. Importantly,
      initial clinical studies have demonstrated encouraging safety and efficacy in
      diseases such as Parkinson disease and spinal muscular atrophy, as well as
      durability of transgene expression. Here, we discuss key considerations and
      challenges in the future design and development of therapeutic AAV vectors,
      highlighting the most promising targets and recent clinical advances.

PMID- 30093652
TI  - Clock gene expression and locomotor activity predict death in the last days of
      life in Drosophila melanogaster.
AB  - The importance of the circadian clock for the regulation of behaviour and
      physiology, and the molecular control of these rhythms by a set of clock genes
      are well defined. The circadian clock deteriorates with advancing age but the
      mechanism underlying is unclear. Here we recorded the expression of two key clock
      genes in young, middle-aged and old Drosophila using transgenic luciferase lines
      reporting period and timeless in vivo. We report a novel marker of imminent death
      in the expression of TIMELESS. In the days immediately preceding death TIMELESS
      expression increased to at least 150% of previous acrophase values (88.0% of n =
      217) and lost circadian rhythmicity, which predicted death equally well in flies
      of different ages and under light and temperature cycles. We suggest this
      transient aberrant clock-gene expression is central to the mechanism of the
      disturbance in circadian behaviour before death (82.7% of n = 342). We also find
      that PERIOD expression in central-clock neurons remained robust with age, however
      PERIOD and TIMELESS in peripheral clocks showed a reduction in both expression
      level and rhythmicity. In conclusion, as flies age the molecular clock gradually
      declines at the peripheral level but continues to function at the central until
      days before death.

PMID- 30093651
TI  - Genome wide identification and experimental validation of Pseudomonas aeruginosa
      Tat substrates.
AB  - In bacteria, the twin-arginine translocation (Tat) pathway allows the export of
      folded proteins through the inner membrane. Proteins targeted to this system are
      synthesized with N-terminal signal peptides bearing a conserved twin-arginine
      motif. The Tat pathway is critical for many bacterial processes including
      pathogenesis and virulence. However, the full set of Tat substrates is unknown in
      many bacteria, and the reliability of in silico prediction methods largely
      uncertain. In this work, we performed a combination of in silico analysis and
      experimental validation to identify a core set of Tat substrates in the
      opportunistic pathogen Pseudomonas aeruginosa. In silico analysis predicted 44
      putative Tat signal peptides in the P. aeruginosa PA14 proteome. We developed an
      improved amidase-based Tat reporter assay to show that 33 of these are real Tat
      signal peptides. In addition, in silico analysis of the full translated genome
      revealed a Tat candidate with a missassigned start codon. We showed that it is a
      new periplasmic protein in P. aeruginosa. Altogether we discovered and validated
      34 Tat substrates. These show little overlap with Escherichia coli Tat
      substrates, and functional analysis points to a general role for the P.
      aeruginosa Tat system in the colonization of environmental niches and
      pathogenicity.

PMID- 30093653
TI  - Exploring the possibilities of dynamical quantum phase transitions in the
      presence of a Markovian bath.
AB  - We explore the possibility of dynamical quantum phase transitions (DQPTs)
      occurring during the temporal evolution of a quenched transverse field Ising
      chain coupled to a particle loss type of bath (local in Jordan-Wigner fermion
      space) using two versions of the Loschmidt overlap (LO), namely, the fidelity
      induced LO and the interferometric phase induced LO. The bath, on the one hand,
      dictates the dissipative evolution following a sudden quench and on the other,
      plays a role in dissipative mixed state preparation in the later part of the
      study. During a dissipative evolution following a sudden quench, no trace of
      DQPTs are revealed in both the fidelity and the interferometric phase approaches;
      however, remarkably the interferometric phase approach reveals the possibility of
      inter-steady state DQPTs in passage from one steady state to the other when the
      system is subjected to a quench after having reached the first steady state. We
      further probe the occurrences of DQPTs when the system evolves unitarily after
      being prepared in a mixed state of engineered purity by ramping the transverse
      field in a linear fashion in the presence of the bath. In this case though the
      fidelity approach fails to indicate any DQPT, the interferometric approach indeed
      unravels the possibility of occurrence of DQPTs which persists even up to a
      considerable loss of purity of the engineered initial state as long as a
      constraint relation involving the dissipative coupling and ramping time (rate) is
      satisfied. This constraint relation also marks the boundary between two
      dynamically inequivalent phases; in one the LO vanishes for the critical momentum
      mode (and hence DQPTs exist) while in the other no such critical mode can exist
      and hence the LO never vanishes.

PMID- 30093654
TI  - Functional Nano-Coating Materials by Michael Addition and Ring-opening
      Polymerization: Reactivity, Molecular Architecture and Refractive index.
AB  - Understanding the molecular interaction and morphology of organic-inorganic
      hybrid materials is an important and fundamental assignment to develop novel high
      performance materials. In this work, we developed two types of hybrid coating
      materials by using different silane coupling agents via Michael addition reaction
      and ring-opening polymerization. The changes in molecular interaction and
      morphology of the hybrid coatings due to chemical composition and curing
      temperature were studied by electron microscopy, spectroscopy and solid state
      29Si nuclear magnetic resonance analysis. Fundamental differences were observed
      in HYBRID I and HYBRID II coatings during the nucleation stage that was dependent
      on the curing temperature. Higher curing temperature of the hybrid coatings
      resulted in improved uniformity and greater crystallinity of dispersed phases,
      and better control of the morphology compared with coatings cured at lower
      temperatures. The higher curing temperature provided more consistent nucleation
      sites for the growth of larger nanostructures of desired characteristics (e.g.,
      size and surface features). There is great flexibility in synthesizingg these
      hybrid materials where different structure and morphology can be achieved to
      produce materials whose applications can range from adhesives to protective
      coatings. Refractive index results revealed that HYBRID I (90  degrees C) coating
      showed higher refractive index than HYBRID II (90  degrees C) coating.

PMID- 30093656
TI  - Dysregulation in Actin Cytoskeletal Organization Drives Increased Stiffness and
      Migratory Persistence in Polyploidal Giant Cancer Cells.
AB  - Polyploidal giant cancer cells (PGCCs) have been observed by pathologists in
      patient tumor samples and are especially prominent in late stage, high grade
      disease or after chemotherapy. However, they are often overlooked due to their
      apparent dormancy. Recent research has shown PGCCs to be chemoresistant and
      express stem-like features, traits associated with disease progression and
      relapse. Here, we show the preferential survival of PGCCs during Paclitaxel (PTX)
      treatment and used multiple particle tracking analysis to probe their unique
      biophysical phenotype. We show that PGCCs have higher inherent cytoplasmic and
      nuclear stiffness in order to withstand the mechanical stress associated with
      their increased size and the chemical stress from PTX treatment. Inhibitor
      studies show the involvement of a dysregulated RhoA-Rock1 pathway and overall
      actin cytoskeletal network as the underlying mechanism for the altered
      biophysical phenotype of PGCCs. Furthermore, PGCCs exhibit a slow but persistent
      migratory phenotype, a trait commonly associated with metastatic dissemination
      and invasiveness. This work demonstrates the clinical relevance and the need to
      study this subpopulation, in order to devise therapeutic strategies to combat
      disease relapse. By highlighting the unique biophysical phenotype of PGCCs, we
      hope to provide unique avenues for therapeutic targeting of these cells in
      disease treatment.

PMID- 30093655
TI  - Arsenic targets Pin1 and cooperates with retinoic acid to inhibit cancer-driving
      pathways and tumor-initiating cells.
AB  - Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) combination safely
      cures fatal acute promyelocytic leukemia, but their mechanisms of action and
      efficacy are not fully understood. ATRA inhibits leukemia, breast, and liver
      cancer by targeting isomerase Pin1, a master regulator of oncogenic signaling
      networks. Here we show that ATO targets Pin1 and cooperates with ATRA to exert
      potent anticancer activity. ATO inhibits and degrades Pin1, and suppresses its
      oncogenic function by noncovalent binding to Pin1's active site. ATRA increases
      cellular ATO uptake through upregulating aquaporin-9. ATO and ATRA, at clinically
      safe doses, cooperatively ablate Pin1 to block numerous cancer-driving pathways
      and inhibit the growth of triple-negative breast cancer cells and tumor
      initiating cells in cell and animal models including patient-derived orthotopic
      xenografts, like Pin1 knockout, which is substantiated by comprehensive protein
      and microRNA analyses. Thus, synergistic targeting of Pin1 by ATO and ATRA offers
      an attractive approach to combating breast and other cancers.

PMID- 30093658
TI  - Universal molecular structures in natural dissolved organic matter.
AB  - Natural dissolved organic matter (DOM) comprises a broad range of dissolved
      organic molecules in aquatic systems and is among the most complex molecular
      mixtures known. Here we show, by comparing detailed structural fingerprints of
      individual molecular formulae in DOM from a set of four marine and one freshwater
      environments, that a major component of DOM is molecularly indistinguishable in
      these diverse samples. Molecular conformity was not only apparent by the co
      occurrence of thousands of identical molecular formulae, but also by identical
      structural features of those isomers that collectively represent a molecular
      formula. The presence of a large pool of compounds with identical structural
      features in DOM is likely the result of a cascade of degradation processes or
      common synthetic pathways that ultimately lead to the formation of a universal
      background, regardless of origin and history of the organic material. This novel
      insight impacts our understanding of long-term turnover of DOM as the underlying
      mechanisms are possibly universal.

PMID- 30093657
TI  - PI3Kdelta hyper-activation promotes development of B cells that exacerbate
      Streptococcus pneumoniae infection in an antibody-independent manner.
AB  - Streptococcus pneumoniae is a major cause of pneumonia and a leading cause of
      death world-wide. Antibody-mediated immune responses can confer protection
      against repeated exposure to S. pneumoniae, yet vaccines offer only partial
      protection. Patients with Activated PI3Kdelta Syndrome (APDS) are highly
      susceptible to S. pneumoniae. We generated a conditional knock-in mouse model of
      this disease and identify a CD19+B220- B cell subset that is induced by PI3Kdelta
      signaling, resides in the lungs, and is correlated with increased susceptibility
      to S. pneumoniae during early phases of infection via an antibody-independent
      mechanism. We show that an inhaled PI3Kdelta inhibitor improves survival rates
      following S. pneumoniae infection in wild-type mice and in mice with activated
      PI3Kdelta. These results suggest that a subset of B cells in the lung can promote
      the severity of S. pneumoniae infection, representing a potential therapeutic
      target.

PMID- 30093659
TI  - Comparison between transoral laser surgery and radiotherapy in the treatment of
      early glottic cancer: A systematic review and meta-analysis.
AB  - A therapeutic decision in the treatment of Tis/T1a glottic carcinoma with
      radiotherapy (RT) or transoral laser surgery (TOS) is still an open issue.
      Oncologic outcome and voice quality may support the choice for the latter To
      conduct a systematic review and meta-analysis to compare oncologic and functional
      outcomes of TOS and RT as treatment options for Tis/T1a glottic cancer.
      Literature research on online databases was carried out. Potentially eligible
      articles were reviewed. Relevant articles were selected and evaluated. There was
      statistical significance favoring patients initially treated with TOS when it
      comes to overall survival, disease-specific survival and larynx preservation. No
      difference in local control was found. TMF, Jitter and Shimmmer measurements
      presented statistically significant results in favor of RT. Self-assessment of
      voice quality (VHI) and f0 showed no statistically significant differences.
      Maximum Phonation Time (MPT) had a better response to RT. There is a trend in
      favor of RT. Tis/T1a glottic cancer patients submitted to TOS had significant
      overall and disease specific survival and had fewer risks of having a total
      laryngectomy, when compared to the radiotherapy group. The self-assessment of
      voice quality and f0 did not show any difference; however, Jitter, Shimmer and
      MPT measurements favored radiotherapy.

PMID- 30093661
TI  - Impact of scribing history and physical notes and procedure reports on
      endoscopist efficiency during routine procedures: a proof-of-concept study.
AB  - BACKGROUND: Efficiency is an important aspect of endoscopic practice that has
      received limited study. We evaluated the impact of scribing electronic pre
      procedure history and physical examinations, and electronic procedure reports on
      endoscopist efficiency. METHODS: We used a stopwatch to measure the time between
      the procedures (scope out to scope in), pre-procedure patient assessment time,
      and procedure report generation time for 180 consecutive procedures performed by
      a single endoscopist with or without a scribe for recording history and physical
      and procedure reports. Schedulers were unaware of whether a scribe would be
      present. RESULTS: Mean times for recording the pre-procedure history and physical
      and procedure reports were reduced by 34% (p = 0.001) and 71% (p < 0.0001),
      respectively, when scribes were used. The mean time saved by the endoscopist from
      scribing the history and the physical and procedure reports was 2.12 and 1.59
      min, respectively. When both processes were scribed, the endoscopist spent 42% (p
      = 0.033) longer in the recovery area (absolute mean increase 1.01 min) compared
      with when no scribes were utilized. The total time saved per 6.5-h procedure
      block with both scribes averaged to 41.7 min. CONCLUSION: The use of scribes to
      record history and physical examination notes and procedure reports saved enough
      endoscopist time to allow additional procedures or longer procedures, or to free
      the time for other tasks.

PMID- 30093660
TI  - Gauss's law for networks directly reveals community boundaries.
AB  - The study of network topology provides insight into the function and behavior of
      physical, social, and biological systems. A natural step towards discovering the
      organizing principles of these complex topologies is to identify a reduced
      network representation using cohesive subgroups or communities. This procedure
      often uncovers the underlying mechanisms governing the functional assembly of
      complex networks. A community is usually defined as a subgraph or a set of nodes
      that has more edges than would be expected from a simple, null distribution of
      edges over the graph. This view drives objective such as modularity. Another
      perspective, corresponding to objectives like conductance or density, is that
      communities are groups of nodes that have extremal properties with respect to the
      number of internal edges and cut edges. Here we show that identifying community
      boundaries rather than communities results in a more accurate decomposition of
      the network into informative components. We derive a network analog of Gauss's
      law that relates a measure of flux through a subgraph's boundary to the
      connectivity among the subgraph's nodes. Our Gauss's law for networks naturally
      characterizes a community as a subgraph with high flux through its boundary.
      Aggregating flux over these boundaries gives rise to a Laplacian and forms the
      basis of our "Laplacian modularity" quality function for community detection that
      is applicable to general network types. This technique allows us to determine
      communities that are both overlapping and hierarchically organized.

PMID- 30093662
TI  - A simple and inexpensive quantitative technique for determining chemical
      sensitivity in Saccharomyces cerevisiae.
AB  - Chemical sensitivity, growth inhibition in response to a chemical, is a powerful
      phenotype that can reveal insight into diverse cellular processes. Chemical
      sensitivity assays are used in nearly every model system, however the yeast
      Saccharomyces cerevisiae provides a particularly powerful platform for discovery
      and mechanistic insight from chemical sensitivity assays. Here we describe a
      simple and inexpensive approach to determine chemical sensitivity quantitatively
      in yeast in the form of half maximal inhibitory concentration (IC50) using common
      laboratory equipment. We demonstrate the utility of this method using chemicals
      commonly used to monitor changes in membrane traffic. When compared to
      traditional agar-based plating methods, this method is more sensitive and can
      detect defects not apparent using other protocols. Additionally, this method
      reduces the experimental protocol from five days to 18 hours for the toxic amino
      acid canavanine. Furthermore, this method provides reliable results using lower
      amounts of chemicals. Finally, this method is easily adapted to additional
      chemicals as demonstrated with an engineered system that activates the spindle
      assembly checkpoint in response to rapamycin with differing efficiencies. This
      approach provides researchers with a cost-effective method to perform chemical
      genetic profiling without specialized equipment.

PMID- 30093663
TI  - Hybrid nanodiamond quantum sensors enabled by volume phase transitions of
      hydrogels.
AB  - Diamond nitrogen-vacancy (NV) center-based magnetometry provides a unique
      opportunity for quantum bio-sensing. However, NV centers are not sensitive to
      parameters such as temperature and pressure, and immune to many biochemical
      parameters such as pH and non-magnetic biomolecules. Here, we propose a scheme
      that can potentially enable the measurement of various biochemical parameters
      using diamond quantum sensing, by employing stimulus-responsive hydrogels as a
      spacing transducer in-between a nanodiamond (ND, with NV centers) and magnetic
      nanoparticles (MNPs). The volume phase transition of hydrogel upon stimulation
      leads to sharp variation in the separation distance between the MNPs and the ND.
      This in turn changes the magnetic field that the NV centers can detect
      sensitively. We construct a temperature sensor under this hybrid scheme and show
      the proof-of-the-principle demonstration of reversible temperature sensing.
      Applications in the detection of other bio-relevant parameters are envisioned if
      appropriate types of hydrogels can be engineered.

PMID- 30093664
TI  - Inhibiting the CD8+ T cell infiltration in the tumor microenvironment after
      radiotherapy is an important mechanism of radioresistance.
AB  - Endogenous immune response participates in tumor control, and radiotherapy has
      immune modulatory capacity, but the role of immune modulation in the tumor
      microenvironment invoked by radiotherapy in radiosensitivity is poorly defined.
      In the present study, a radio-resistant melanoma cell line was obtained after
      repeated irradiation to the parental tumor in C57BL/6 mice. Radiotherapy resulted
      in aggregation of CD8+ and CD3+ T cells, and decrease of myeloid-derived
      suppressor cells and dendritic cells in the parental tumor, but not in the
      resistant tumors. CD4+ T cells and B cells did not change significantly. The CD8+
      T cell infiltration after radiotherapy is important for tumor response, because
      in the nude mice and CD8+ T cell-depleted C57BL/6 mice, the parental and
      resistant tumor has similar radiosensitivity. Patients with good radiation
      response had more CD8+ T cells aggregation after radiotherapy. Radiotherapy
      resulted in robust transcription of T cell chemoattractant in the parental cells,
      and the expression of CCL5 was much higher. These results reveal a novel
      mechanism of radioresistance, tumor cells inhibit the infiltration of CD8+ T cell
      after radiotherapy and become radioresistant. Increasing CD8+ T cell infiltration
      after RT may be an effective way to improve tumor radiosensitivity.

PMID- 30093666
TI  - New locus reveals the genetic architecture of sex reversal in the Chinese tongue
      sole (Cynoglossus semilaevis).
AB  - Sex reversal in insects, amphibians, reptiles, and fishes is a complicated and
      interesting biological phenomenon. Sex reversal changes the sex ratio of
      populations and may complicate breeding schemes. In the Chinese tongue sole
      (Cynoglossus semilaevis), genetic females may change into pseudomales, thereby
      increasing aquaculture costs because of the lower growth rate of the males than
      that of the females. Here we identify a new locus associated with sex reversal;
      this single nucleotide polymorphism (SNP) is located in the third intron of the
      doublesex and mab-3 related transcription factor 1 (Dmrt1) gene on the Z
      chromosome (named Cyn_Z_8564889) and has two alleles, A and G. Cyn_Z_8564889
      regulates sex reversal interactively with our previously detected SNP
      (Cyn_Z_6676874), with the genetic females simultaneously carrying the T allele of
      Cyn_Z_6676874 and the A allele of Cyn_Z_8564889 changing into pseudomales. Other
      Dmrt1 polymorphisms were detected, which formed two haplotypes. Two SNPs in the
      second exon of Dmrt1 result in amino acid changes, suggesting that Dmrt1 is
      essential in sex reversal. We also verified that pseudomales produce no or little
      W sperm. The interaction and linkage between Cyn_Z_6676874 and Cyn_Z_8564889 and
      the absence of W sperm from pseudomales unravel the genetic architecture of sex
      reversal in C. semilaevis.

PMID- 30093665
TI  - Role of VTA dopamine neurons and neuroligin 3 in sociability traits related to
      nonfamiliar conspecific interaction.
AB  - Atypical habituation and aberrant exploration of novel stimuli have been related
      to the severity of autism spectrum disorders (ASDs), but the underlying neuronal
      circuits are unknown. Here we show that chemogenetic inhibition of dopamine (DA)
      neurons of the ventral tegmental area (VTA) attenuates exploration toward
      nonfamiliar conspecifics and interferes with the reinforcing properties of
      nonfamiliar conspecific interaction in mice. Exploration of nonfamiliar stimuli
      is associated with the insertion of GluA2-lacking AMPA receptors at excitatory
      synapses on VTA DA neurons. These synaptic adaptations persist upon repeated
      exposure to social stimuli and sustain conspecific interaction. Global or VTA DA
      neuron-specific loss of the ASD-associated synaptic adhesion molecule neuroligin
      3 alters the behavioral response toward nonfamiliar conspecifics and the
      reinforcing properties of conspecific interaction. These behavioral deficits are
      accompanied by an aberrant expression of AMPA receptors and an occlusion of
      synaptic plasticity. Altogether, these findings link impaired exploration of
      nonfamiliar conspecifics to VTA DA neuron dysfunction in mice.

PMID- 30093668
TI  - Behavioural patterns of electrolyte repletion in intensive care units: lessons
      from a large electronic dataset.
AB  - Repletion of electrolytes often depends on provider-specific behavior and
      hospital policy. We examined the pattern of electrolyte repletion across several
      intensive care units (ICU) in a large healthcare system from 2010-2015. This
      included 109 723 potassium repletions, 51 833 magnesium repletions, 2 306 calcium
      repletions, 8 770 phosphate repletions, and 3 128 249 visit-days over 332 018
      visits. Potassium, magnesium, and calcium were usually repleted within the
      institutional reference range. In contrast, the bulk of phosphate repletion was
      done with pre-repletion serum level below the reference range. The impact of
      repletion on post-repletion levels was significant but uniformly small. The pre
      repletion serum level had a significant inverse correlation with the post
      repletion level of each electrolyte. Potassium, magnesium and phosphate follow-up
      labs were scheduled in 9-10 hours after their repletion. In contrast, calcium was
      rechecked in less than 20 minutes. Routine repletion of potassium, magnesium and
      calcium had no effect on the incidence of tachyarrhythmias. We estimated the
      expense from electrolyte repletion within the reference range was approximately
      $1.25 million. Absent a specific clinical indication, repleting electrolytes when
      the serum concentration are within normative values may represent an avenue for
      cost savings, staff burden unload and potential reduction in frequency of
      complications in the ICUs.

PMID- 30093667
TI  - Dual stimuli-responsive rotaxane-branched dendrimers with reversible dimension
      modulation.
AB  - With the aim of mimicking biological machines, in which the delicate arrangement
      of nanomechanical units lead to the output of specific functions upon the
      external stimulus, the construction of dual stimuli-responsive rotaxane-branched
      dendrimers was realized in this study. Starting from a switchable organometallic
      [2]rotaxane precursor, the employment of a controllable divergent approach
      allowed for the successful synthesis of a family of rotaxane-branched dendrimers
      up to the third generation with 21 switchable rotaxane moieties located on each
      branch. More importantly, upon the addition and removal of dimethylsulfoxide
      (DMSO) molecule or acetate anion as the external stimulus, the amplified
      responsiveness of the switchable rotaxane units endowed the resultant rotaxane
      branched dendrimers the solvent- or anion-controlled molecular motions, thus
      leading to the dimension modulation. Therefore, we successfully constructed a
      family of rotaxane-branched dendrimers with dual stimuli-responsiveness that will
      be a privileged platform for the construction of dynamic supramolecular
      materials.

PMID- 30093669
TI  - Small molecule inhibitors of RAS-effector protein interactions derived using an
      intracellular antibody fragment.
AB  - Targeting specific protein-protein interactions (PPIs) is an attractive concept
      for drug development, but hard to implement since intracellular antibodies do not
      penetrate cells and most small-molecule drugs are considered unsuitable for PPI
      inhibition. A potential solution to these problems is to select intracellular
      antibody fragments to block PPIs, use these antibody fragments for target
      validation in disease models and finally derive small molecules overlapping the
      antibody-binding site. Here, we explore this strategy using an anti-mutant RAS
      antibody fragment as a competitor in a small-molecule library screen for
      identifying RAS-binding compounds. The initial hits are optimized by structure
      based design, resulting in potent RAS-binding compounds that interact with RAS
      inside the cells, prevent RAS-effector interactions and inhibit endogenous RAS
      dependent signalling. Our results may aid RAS-dependent cancer drug development
      and demonstrate a general concept for developing small compounds to replace
      intracellular antibody fragments, enabling rational drug development to target
      validated PPIs.

PMID- 30093672
TI  - Paul Delos Boyer (1918-2018).

PMID- 30093670
TI  - Control of transmembrane charge transfer in cytochrome c oxidase by the membrane
      potential.
AB  - The respiratory chain in mitochondria is composed of membrane-bound proteins that
      couple electron transfer to proton translocation across the inner membrane. These
      charge-transfer reactions are regulated by the proton electrochemical gradient
      that is generated and maintained by the transmembrane charge transfer. Here, we
      investigate this feedback mechanism in cytochrome c oxidase in intact inner
      mitochondrial membranes upon generation of an electrochemical potential by
      hydrolysis of ATP. The data indicate that a reaction step that involves proton
      uptake to the catalytic site and presumably proton translocation is impaired by
      the potential, but electron transfer is not affected. These results define the
      order of electron and proton-transfer reactions and suggest that the proton pump
      is regulated by the transmembrane electrochemical gradient through control of
      internal proton transfer rather than by control of electron transfer.

PMID- 30093671
TI  - MLL1 is essential for retinal neurogenesis and horizontal inner neuron integrity.
AB  - Development of retinal structure and function is controlled by cell type-specific
      transcription factors and widely expressed co-regulators. The latter includes the
      mixed-lineage leukemia (MLL) family of histone methyltransferases that catalyze
      histone H3 lysine 4 di- and tri-methylation associated with gene activation. One
      such member, MLL1, is widely expressed in the central nervous system including
      the retina. However, its role in retinal development is unknown. To address this
      question, we knocked out Mll1 in mouse retinal progenitors, and discovered that
      MLL1 plays multiple roles in retinal development by regulating progenitor cell
      proliferation, cell type composition and neuron-glia balance, maintenance of
      horizontal neurons, and formation of functional synapses between neuronal layers
      required for visual signal transmission and processing. Altogether, our results
      suggest that MLL1 is indispensable for retinal neurogenesis and function
      development, providing a new paradigm for cell type-specific roles of known
      histone modifying enzymes during CNS tissue development.

PMID- 30093674
TI  - Monetary Incentives Modulate Feedback-related Brain Activity.
AB  - Previous research has shown that feedback evaluation is sensitive to monetary
      incentive. We investigated whether this sensitivity is driven by motivational
      salience (the difference between both rewarding and punishing events versus
      neutral events) or by motivational valence (the difference between rewarding and
      punishing events). Fifty-seven participants performed a monetary incentive delay
      task under a gain context, a loss context, and a neutral context with their
      electroencephalogram recorded. During the time domain, the feedback-related
      negativity (FRN) showed a motivational salience effect whereas the P3 displayed a
      reward valence effect. During the time-frequency domain, we observed a
      motivational salience effect for phase-locked theta power regardless of
      performance feedback, but a reward valence effect for non-phase-locked theta
      power in response to unsuccessful feedback. Moreover, we found a reward valence
      effect for phase-locked delta. These findings thus suggest that the affective
      modulation on feedback evaluation can be driven either by motivational valence or
      by motivational salience, which depends on the temporal dynamics (the FRN vs. the
      P3), the frequency dynamics (theta vs. delta power), as well as the phase
      dynamics (evoked vs. induced power).

PMID- 30093675
TI  - c-Src regulates cargo transit via the Golgi in pancreatic acinar cells.
AB  - The exocrine pancreatic acinar cell is unique for its rapid protein synthesis and
      packaging in zymogen granules (ZGs). However, while crucial to the pathogenesis
      of pancreatitis, the signaling involved in the transit of proteins via the Golgi
      is poorly understood in these cells. Noting the evidence of c-Src in regulating
      transit of cargo via the Golgi in other systems, we explored this in acinar
      cells. Stimulation of ZG formation with dexamethasone activated Src and increased
      the Golgi area in acinar cells. c-Src localized to the microsomes of acinar cells
      on immunofluorescence and subcellular fractionation. While other Src family
      members had no effect on the Golgi markers P115 and GM130, active c-Src increased
      the Golgi area these stained, extending them into the ER. Src inhibition reduced
      amylase staining outside the Golgi and increased it in a stack like Golgi
      morphology. In vivo pharmacologic inhibition or acinar specific genetic deletion
      of c-Src reduced ZG number and staining of amylase in ZGs along with increasing
      amylase retention in the microsomal fraction. Morphologically this was associated
      with smaller Golgi stacks, and dilation of the endoplasmic reticulum. Therefore
      the role c-Src regulated Golgi function, ZG formation and microsomal zymogen
      transit in acinar cells needs to be explored in pancreatitis.

PMID- 30093673
TI  - Structure of the essential peptidoglycan amidotransferase MurT/GatD complex from
      Streptococcus pneumoniae.
AB  - The universality of peptidoglycan in bacteria underlies the broad spectrum of
      many successful antibiotics. However, in our times of widespread resistance, the
      diversity of peptidoglycan modifications offers a variety of new antibacterials
      targets. In some Gram-positive species such as Streptococcus pneumoniae,
      Staphylococcus aureus, or Mycobacterium tuberculosis, the second residue of the
      peptidoglycan precursor, D-glutamate, is amidated into iso-D-glutamine by the
      essential amidotransferase MurT/GatD complex. Here, we present the structure of
      this complex at 3.0 A resolution. MurT has central and C-terminal domains similar
      to Mur ligases with a cysteine-rich insertion, which probably binds zinc,
      contributing to the interface with GatD. The mechanism of amidation by MurT is
      likely similar to the condensation catalyzed by Mur ligases. GatD is a
      glutaminase providing ammonia that is likely channeled to the MurT active site
      through a cavity network. The structure and assay presented here constitute a
      knowledge base for future drug development studies.

PMID- 30093676
TI  - Greenland ice mass loss during the Younger Dryas driven by Atlantic Meridional
      Overturning Circulation feedbacks.
AB  - Understanding feedbacks between the Greenland Ice Sheet (GrIS) and the Atlantic
      Meridional Overturning Circulation (AMOC) is crucial for reducing uncertainties
      over future sea level and ocean circulation change. Reconstructing past GrIS
      dynamics can extend the observational record and elucidate mechanisms that
      operate on multi-decadal timescales. We report a highly-constrained last glacial
      vertical profile of cosmogenic isotope exposure ages from Sermilik Fjord, a
      marine-terminating ice stream in the southeast sector of the GrIS. Our
      reconstruction reveals substantial ice-mass loss throughout the Younger Dryas
      (12.9-11.7 ka), a period of marked atmospheric and sea-surface cooling. Earth
      system modelling reveals that southern GrIS marginal melt was likely driven by
      strengthening of the Irminger Current at depth due to a weakening of the AMOC
      during the Younger Dryas. This change in North Atlantic circulation appears to
      have drawn warm subsurface waters to southeast Greenland despite markedly cooler
      sea surface temperatures, enhancing thermal erosion at the grounding lines of
      palaeo ice-streams, supporting interpretation of regional marine-sediment cores.
      Given current rates of GrIS meltwater input into the North Atlantic and the
      vulnerability of major ice streams to water temperature changes at the grounding
      line, this mechanism has important implications for future AMOC changes and
      northern hemisphere heat transport.

PMID- 30093677
TI  - Bifidobacterium adolescentis is intrinsically resistant to antitubercular drugs.
AB  - Multiple mutations in the beta subunit of the RNA polymerase (rpobeta) of
      Mycobacterium tuberculosis (Mtb) are the primary cause of resistance to rifamycin
      (RIF). In the present study, bifidobacterial rpobeta sequences were analyzed to
      characterize the mutations that contribute to the development of intrinsic
      resistance to RIF, isoniazid, streptomycin and pyrazinamide. Sequence variations,
      which mapped to cassettes 1 and 2 of the rpobeta pocket, are also found in
      multidrug-resistant Mtb (MDR Mtb). Growth curves in the presence of osmolytes and
      different concentrations of RIF showed that the bacteria adapted rapidly by
      shortening the growth curve lag time. Insight into the adapted rpobeta DNA
      sequences revealed that B. adolescentis harbored mutations both in the RIF pocket
      and in regions outside the pocket. The minimum inhibitory concentrations (MICs)
      and mutant prevention concentrations (MPCs) indicated that B. longum, B.
      adolescentis and B. animalis are resistant to antitubercular drugs. 3D-homology
      modeling and binding interaction studies using computational docking suggested
      that mutants had reduced binding affinity towards RIF. RIF-exposed/resistant
      bacteria exhibited variant protein profiles along with morphological differences,
      such as elongated and branched cells, surface conversion from rough to smooth,
      and formation of a concentrating ring.

PMID- 30093679
TI  - Late Cenozoic unification of East and West Antarctica.
AB  - The kinematic evolution of the West Antarctic rift system has important
      consequences for regional and global geodynamics. However, due to the lack of
      Neogene seafloor spreading at the plate boundary and despite being poorly
      resolved, East-West Antarctic motion was assumed to have ended abruptly at 26
      million years ago. Here we present marine magnetic data collected near the
      northern edge of the rift system showing that motion between East and West
      Antarctica lasted until the middle Neogene (~11 million years ago), long after
      the cessation of the known mid-Cenozoic pulse of motion. We calculate new
      rotation parameters for the early Neogene that provide the kinematic framework to
      understand the varied lithospheric settings of the Transantarctic Mountains and
      the tectono-volcanic activity within the rift. Incorporation of the Antarctic
      plate motion into the global plate circuit has major implications for the
      predicted Neogene motion of the Pacific Plate relative to the rest of the plates.

PMID- 30093678
TI  - Reassessment of pre-industrial fire emissions strongly affects anthropogenic
      aerosol forcing.
AB  - Uncertainty in pre-industrial natural aerosol emissions is a major component of
      the overall uncertainty in the radiative forcing of climate. Improved
      characterisation of natural emissions and their radiative effects can therefore
      increase the accuracy of global climate model projections. Here we show that
      revised assumptions about pre-industrial fire activity result in significantly
      increased aerosol concentrations in the pre-industrial atmosphere. Revised global
      model simulations predict a 35% reduction in the calculated global mean cloud
      albedo forcing over the Industrial Era (1750-2000 CE) compared to estimates using
      emissions data from the Sixth Coupled Model Intercomparison Project. An estimated
      upper limit to pre-industrial fire emissions results in a much greater (91%)
      reduction in forcing. When compared to 26 other uncertain parameters or inputs in
      our model, pre-industrial fire emissions are by far the single largest source of
      uncertainty in pre-industrial aerosol concentrations, and hence in our
      understanding of the magnitude of the historical radiative forcing due to
      anthropogenic aerosol emissions.

PMID- 30093680
TI  - Virtual Recovery of Content from X-Ray Micro-Tomography Scans of Damaged Historic
      Scrolls.
AB  - There is a large body of historical documents that are too fragile to be opened
      or unrolled, making their contents inaccessible. Recent improvements in X-ray
      scanning technology and computer vision techniques make it possible to perform a
      "virtual" unrolling of such documents. We describe a novel technique to process a
      stack of 3D X-ray images to identify the surface of parchment scrolls, unroll
      them, and create a visualization of their written contents. Unlike existing
      techniques, we can handle even challenging cases with minimal manual interaction.
      Our novel approach was deployed on two 15th and 16th century damaged historic
      scrolls from the manors of Bressingham and Diss Heywood. The former has become
      fused, probably due to exposure to moisture, and cannot be fully unrolled. The
      latter was severely burnt several hundred years ago, becoming thoroughly charred,
      heat-shrunken, and distorted, with all the sheets now brittle and fused together.
      Our virtual unrolling revealed text that has been hidden for centuries.

PMID- 30093681
TI  - Tamibarotene maintenance improved relapse-free survival of acute promyelocytic
      leukemia: a final result of prospective, randomized, JALSG-APL204 study.
AB  - Between April 2004 and December 2010, we conducted a prospective randomized
      controlled study comparing tamibarotene with all-trans retinoic acid (ATRA) in
      the maintenance therapy of newly diagnosed acute promyelocytic leukemia (APL),
      and here report the final results of this study with a median follow-up of 7.3
      years. Of 344 eligible patients who had received ATRA and chemotherapy, 319 (93%)
      achieved complete remission (CR). After completion of three courses of
      consolidation chemotherapy, 269 patients in molecular remission underwent
      maintenance randomization, 135 to ATRA (45 mg/m2 daily), and 134 to tamibarotene
      (6 mg/m2 daily) for 14 days every 3 months for 2 years. The primary endpoint was
      relapse-free survival (RFS). The 7-year RFS was 84% in the ATRA arm and 93% in
      the tamibarotene arm (p = 0.027, HR = 0.44, 95% CI, 0.21 to 0.93). The difference
      was prominent in high-risk patients with initial leukocytes >= 10.0 * 109/L (62%
      vs. 89%; p = 0.034). Tamibarotene was significantly superior to ATRA by
      decreasing relapse in high-risk patients. Overall survival after randomization
      did not differ (96% vs. 97%; p = 0.520). Secondary hematopoietic disorders
      developed in nine patients, secondary malignancies in 11, and grade 3 or more
      late cardiac comorbidities in three. These late complications did not differ
      between the two arms.

PMID- 30093682
TI  - Isolation and characterisation of alveolar type II pneumocytes from adult bovine
      lung.
AB  - Alveolar type II (ATII) cells play a key role as part of the distal lung
      epithelium, including roles in the innate immune response and as self-renewing
      progenitors to replace alveolar type I (ATI) cells during regeneration of the
      alveolar epithelium. Their secretion of surfactant protein helps to maintain
      homeostasis in the distal lung and exert protective, antimicrobial properties.
      Despite the cell's crucial roles, they remain difficult to study, in part due to
      inefficient and expensive isolation methods, a propensity to differentiate into
      alveolar type I cells in culture and susceptibility to fibroblast overgrowth from
      primary isolations. Published methods of isolation often require specialist
      technology, negatively impacting the development of in vitro models of disease,
      including bovine tuberculosis (BTB), a serious re-emerging disease in both
      animals and humans worldwide. We present here a simple and cost-effective method
      that may be utilised in the generation of bovine primary ATII cells. These
      exhibit an ATII phenotype in 2D and 3D culture in our studies and are conducive
      to further study of the role of ATII cells in bovine respiratory diseases.

PMID- 30093683
TI  - Low temperature a/b nanotwins in Ni50Mn25+xGa25-x Heusler alloys.
AB  - We have found low temperature a/b nanotwins having (110) twinning plane in a five
      layered modulated martensite phase of Ni50Mn25+xGa25-x (at. %) Heusler alloys and
      identified the particular region in phase diagram where the nanotwinning occurs.
      Evolution of the structure with decreasing temperature was studied by X-ray
      diffraction using single crystals exhibiting magnetic shape memory effect. The
      merging of (400) and (040) lines upon cooling for 2.6 < x < 3.5 indicated a/b
      nanotwinning originating from the refinement of initially coarse a/b twins.
      Refinement of the twins with decreasing temperature was observed directly using
      scanning electron microscopy. The prerequisite for nanotwinning is an extremely
      low twin boundary energy, which we estimated using first-principles calculations
      to be 0.16 meV/A2. As the nanotwinning distorts the relation between the crystal
      lattice and the X-ray diffraction pattern, it should be taken into consideration
      in structural studies of Ni-Mn-Ga Heusler alloys.

PMID- 30093684
TI  - Schistosomiasis.
AB  - Schistosomiasis (bilharzia) is a neglected tropical disease caused by parasitic
      flatworms (blood flukes) of the genus Schistosoma, with considerable morbidity in
      parts of the Middle East, South America, Southeast Asia and, particularly, in sub
      Saharan Africa. Infective larvae grow in an intermediate host (fresh-water
      snails) before penetrating the skin of the definitive human host. Mature adult
      worms reside in the mesenteric (Schistosoma mansoni and Schistosoma japonicum) or
      pelvic (Schistosoma haematobium) veins, where female worms lay eggs, which are
      secreted in stool or urine. Eggs trapped in the surrounding tissues and organs,
      such as the liver and bladder, cause inflammatory immune responses (including
      granulomas) that result in intestinal, hepato-splenic or urogenital disease.
      Diagnosis requires the detection of eggs in excreta or worm antigens in the
      serum, and sensitive, rapid, point-of-care tests for populations living in
      endemic areas are needed. The anti-schistosomal drug praziquantel is safe and
      efficacious against adult worms of all the six Schistosoma spp. infecting humans;
      however, it does not prevent reinfection and the emergence of drug resistance is
      a concern. Schistosomiasis elimination will require a multifaceted approach,
      including: treatment; snail control; information, education and communication;
      improved water, sanitation and hygiene; accurate diagnostics; and surveillance
      response systems that are readily tailored to social-ecological settings.

PMID- 30093685
TI  - Systematic identification of non-coding pharmacogenomic landscape in cancer.
AB  - Emerging evidence has shown long non-coding RNAs (lncRNAs) play important roles
      in cancer drug response. Here we report a lncRNA pharmacogenomic landscape by
      integrating multi-dimensional genomic data of 1005 cancer cell lines and drug
      response data of 265 anti-cancer compounds. Using Elastic Net (EN) regression,
      our analysis identifies 27,341 lncRNA-drug predictive pairs. We validate the
      robustness of the lncRNA EN-models using two independent cancer pharmacogenomic
      datasets. By applying lncRNA EN-models of 49 FDA approved drugs to the 5605 tumor
      samples from 21 cancer types, we show that cancer cell line based lncRNA EN
      models can predict therapeutic outcome in cancer patients. Further lncRNA-pathway
      co-expression analysis suggests lncRNAs may regulate drug response through drug
      metabolism or drug-target pathways. Finally, we experimentally validate that
      EPIC1, the top predictive lncRNA for the Bromodomain and Extra-Terminal motif
      (BET) inhibitors, strongly promotes iBET762 and JQ-1 resistance through
      activating MYC transcriptional activity.

PMID- 30093688
TI  - Does tau pathology activate jumping genes?

PMID- 30093686
TI  - Resistance to retinopathy development in obese, diabetic and hypertensive ZSF1
      rats: an exciting model to identify protective genes.
AB  - Diabetic retinopathy (DR) is one of the major complications of diabetes, which
      eventually leads to blindness. Up to date, no animal model has yet shown all the
      co-morbidities often observed in DR patients. Here, we investigated whether obese
      42 weeks old ZSF1 rat, which spontaneously develops diabetes, hypertension and
      obesity, would be a suitable model to study DR. Although arteriolar tortuosity
      increased in retinas from obese as compared to lean (hypertensive only) ZSF1
      rats, vascular density pericyte coverage, microglia number, vascular morphology
      and retinal thickness were not affected by diabetes. These results show that,
      despite high glucose levels, obese ZSF1 rats did not develop DR. Such
      observations prompted us to investigate whether the expression of genes, possibly
      able to contain DR development, was affected. Accordingly, mRNA sequencing
      analysis showed that genes (i.e. Npy and crystallins), known to have a protective
      role, were upregulated in retinas from obese ZSF1 rats. Lack of retina damage,
      despite obesity, hypertension and diabetes, makes the 42 weeks of age ZSF1 rats a
      suitable animal model to identify genes with a protective function in DR. Further
      characterisation of the identified genes and downstream pathways could provide
      more therapeutic targets for the treat DR.

PMID- 30093687
TI  - Identification of recurrent USP48 and BRAF mutations in Cushing's disease.
AB  - Cushing's disease results from corticotroph adenomas of the pituitary that
      hypersecrete adrenocorticotropin (ACTH), leading to excess glucocorticoid and
      hypercortisolism. Mutations of the deubiquitinase gene USP8 occur in 35-62% of
      corticotroph adenomas. However, the major driver mutations in USP8 wild-type
      tumors remain elusive. Here, we report recurrent mutations in the deubiquitinase
      gene USP48 (predominantly encoding p.M415I or p.M415V; 21/91 subjects) and BRAF
      (encoding p.V600E; 15/91 subjects) in corticotroph adenomas with wild-type USP8.
      Similar to USP8 mutants, both USP48 and BRAF mutants enhance the promoter
      activity and transcription of the gene encoding proopiomelanocortin (POMC), which
      is the precursor of ACTH, providing a potential mechanism for ACTH overproduction
      in corticotroph adenomas. Moreover, primary corticotroph tumor cells harboring
      BRAF V600E are sensitive to the BRAF inhibitor vemurafenib. Our study thus
      contributes to the understanding of the molecular mechanism of the pathogenesis
      of corticotroph adenoma and informs therapeutic targets for this disease.

PMID- 30093690
TI  - Quantum phases for moving charges and dipoles in an electromagnetic field and
      fundamental equations of quantum mechanics.
AB  - We analyze the quantum phase effects for point-like charges and electric
      (magnetic) dipoles under a natural assumption that the observed phase for a
      dipole represents the sum of corresponding phases for charges composing this
      dipole. This way we disclose two novel quantum phases for charged particles,
      which we named as complementary electric Aharonov-Bohm (A-B) phase and
      complementary magnetic A-B phase, respectively. We reveal that these phases are
      derived from the Schrodinger equation only in the case, where the operator of
      momentum is re-defined via the replacement of the canonical momentum of particle
      by the sum of its mechanical momentum and interactional field momentum for a
      system of charged particles. The related alteration should be introduced to Klein
      Gordon and Dirac equations, too, and implications of this modification are
      discussed.

PMID- 30093689
TI  - A single N1-methyladenosine on the large ribosomal subunit rRNA impacts locally
      its structure and the translation of key metabolic enzymes.
AB  - The entire chemical modification repertoire of yeast ribosomal RNAs and the
      enzymes responsible for it have recently been identified. Nonetheless, in most
      cases the precise roles played by these chemical modifications in ribosome
      structure, function and regulation remain totally unclear. Previously, we
      demonstrated that yeast Rrp8 methylates m1A645 of 25S rRNA in yeast. Here, using
      mung bean nuclease protection assays in combination with quantitative RP-HPLC and
      primer extension, we report that 25S/28S rRNA of S. pombe, C. albicans and humans
      also contain a single m1A methylation in the helix 25.1. We characterized
      nucleomethylin (NML) as a human homolog of yeast Rrp8 and demonstrate that NML
      catalyzes the m1A1322 methylation of 28S rRNA in humans. Our in vivo structural
      probing of 25S rRNA, using both DMS and SHAPE, revealed that the loss of the Rrp8
      catalyzed m1A modification alters the conformation of domain I of yeast 25S rRNA
      causing translation initiation defects detectable as halfmers formation, likely
      because of incompetent loading of 60S on the 43S-preinitiation complex.
      Quantitative proteomic analysis of the yeast Deltarrp8 mutant strain using 2D
      DIGE, revealed that loss of m1A645 impacts production of specific set of proteins
      involved in carbohydrate metabolism, translation and ribosome synthesis. In
      mouse, NML has been characterized as a metabolic disease-associated gene linked
      to obesity. Our findings in yeast also point to a role of Rrp8 in primary
      metabolism. In conclusion, the m1A modification is crucial for maintaining an
      optimal 60S conformation, which in turn is important for regulating the
      production of key metabolic enzymes.

PMID- 30093691
TI  - Quantum coherence of multiple excitons governs absorption cross-sections of
      PbS/CdS core/shell nanocrystals.
AB  - Multiple excitons in semiconductor nanocrystals have been extensively studied
      with respect to unique carrier dynamics including quantized Auger recombination
      and implementation in optoelectronic devices such as solar cells and
      photodetectors. However, the generation mechanism of multiple excitons still
      remains unclear. Here, we study instantaneous and delayed multiple exciton
      generation processes in PbS/CdS core/shell nanocrystals. The absorption cross
      sections of biexcitons and triexcitons are identical to that of single excitons
      under instantaneous excitation with a single pulse. In contrast, the delayed
      excitation using double pulses shows a reduction of the biexciton and triexciton
      absorption cross-sections. Our theoretical analysis reveals that the excitonic
      coherence assists the generation of multiple excitons and that the reduction of
      multiple exciton absorption cross-sections is caused by the reduction of coherent
      excitation pathways. We clarify that exciton coherences play a key role in
      multiple exciton generation processes and seamlessly connect the identical and
      reduced multiple exciton absorption cross-sections.

PMID- 30093693
TI  - Yu-Shiba-Rusinov bound states induced by a spin flipper in the vicinity of a s
      wave superconductor.
AB  - We theoretically study the formation and characteristics of Yu-Shiba-Rusinov
      bound states within the superconducting gap using a BTK approach in presence of a
      spin flipper (high spin magnetic impurity). We focus on the zero energy in the
      conductance spectra and show how a peak is formed at E = 0 due to flipping of the
      magnetic impurity spin, but for no flip case a dip forms at E = 0 in the
      conductance spectra. This E = 0 conductance peak is almost quantized at 2e2/h
      values, however it arises due to non-topological reasons in contrast to the E = 0
      peak formed due to Majorana states.

PMID- 30093692
TI  - The functional relations among motor-based prediction, sensory goals and feedback
      in learning non-native speech sounds: Evidence from adult Mandarin Chinese
      speakers with an auditory feedback masking paradigm.
AB  - Previous studies in speech production and acquisition have mainly focused on how
      feedback vs. goals and feedback vs. prediction regulate learning and speech
      control. The present study investigated the less studied mechanism-prediction vs.
      goals in the context of adult Mandarin speakers' acquisition of non-native
      sounds, using an auditory feedback masking paradigm. Participants were asked to
      learn two types of non-native vowels: /o/ and /o/-the former being less similar
      than the latter to Mandarin vowels, either in feedback available or feedback
      masked conditions. The results show that there was no significant improvement in
      learning the two targets when auditory feedback was masked. This suggests that
      motor-based prediction could not directly compare with sensory goals for adult
      second language acquisition. Furthermore, auditory feedback can help achieve
      learning only if the competition between prediction and goals is minimal, i.e.,
      when target sounds are distinct from existing sounds in one's native speech. The
      results suggest motor-based prediction and sensory goals may share a similar
      neural representational format, which could result in a competing relation in
      neural recourses in speech learning. The feedback can conditionally overcome such
      interference between prediction and goals. Hence, the present study further
      probed the functional relations among key components (prediction, goals and
      feedback) of sensorimotor integration in speech learning.

PMID- 30093694
TI  - Schistosomiasis.

PMID- 30093695
TI  - Mregs kick-start transplant tolerance.

PMID- 30093696
TI  - Radiocarbon analysis of modern olive wood raises doubts concerning a crucial
      piece of evidence in dating the Santorini eruption.
AB  - Charred olive wood is abundant in the archaeological record, especially around
      the Mediterranean. As the outermost ring closest to the bark is assumed to
      represent the latest time that the tree was alive, the radiocarbon date obtained
      from the outermost rings of an olive branch buried during the Santorini volcanic
      eruption is regarded as crucial evidence for the date of this cataclysmic event.
      The date of this eruption has far reaching consequences in the archaeology of the
      Aegean, Egypt and the Levant, and the understanding of their interconnections. We
      analyzed the radiocarbon concentrations in cross-sections from a modern olive
      tree trunk as well as from a living branch, and obtained near-annual resolution
      dates using the radiocarbon "bomb peak". In both cases we show that radiocarbon
      dates of the last formed wood along the circumference are not chronologically
      homogenous, and can differ by up to a few decades. Thus the outermost wood layer
      does not necessarily represent the date of the last year of growth. These
      findings challenge the interpretation of the results obtained from dating the
      olive branch from the Santorini volcanic eruption, as it could predate the
      eruption by a few decades. In addition, our results are also significant for any
      future studies based on archaeologically preserved olive wood.

PMID- 30093697
TI  - TPA-023 attenuates subchronic phencyclidine-induced declarative and reversal
      learning deficits via GABAA receptor agonist mechanism: possible therapeutic
      target for cognitive deficit in schizophrenia.
AB  - GABAergic drugs are of interest for the treatment of anxiety, depression, bipolar
      disorder, pain, cognitive impairment associated with schizophrenia (CIAS), and
      other neuropsychiatric disorders. Some evidence suggests that TPA-023, (7-(1,1
      dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4
      triazolo[4,3-b] pyridazine), a GABAA alpha2,3 subtype-selective GABAA partial
      agonist and alpha1/5 antagonist, and the neurosteroid, pregnenolone sulfate, a
      GABAA antagonist, may improve CIAS in pilot clinical trials. The goal of this
      study was to investigate the effect of TPA-023 in mice after acute or subchronic
      (sc) treatment with the N-methyl-D-aspartate receptor (NMDAR) antagonist,
      phencyclidine (PCP), on novel object recognition (NOR), reversal learning (RL),
      and locomotor activity (LMA) in rodents. Acute TPA-023 significantly reversed
      scPCP-induced NOR and RL deficits. Co-administration of sub-effective dose (SED)
      TPA-023 with SEDs of the atypical antipsychotic drug, lurasidone, significantly
      potentiated the effect of TPA-023 in reversing the scPCP-induced NOR deficit.
      Further, scTPA-023 co-administration significantly prevented scPCP-induced NOR
      deficit for 5 weeks. Also, administration of TPA-023 for 7 days following scPCP
      reversed the NOR deficit for 1 week. However, TPA-023 did not blunt acute PCP
      induced hyperactivity, suggesting lack of efficacy as a treatment for psychosis.
      Systemic TPA-023 significantly blocked lurasidone-induced increases in cortical
      acetylcholine, dopamine, and glutamate without affecting increases in
      norepinephrine and with minimal effect on basal release of these
      neurotransmitters. TPA-023 significantly inhibited PCP-induced cortical and
      striatal dopamine, serotonin, norepinephrine, and glutamate efflux. These results
      suggest that TPA-023 and other GABAA agonists may be of benefit to treat CIAS.

PMID- 30093698
TI  - Efficacy of typical and atypical antipsychotic medication on hostility in
      patients with psychosis-spectrum disorders: a review and meta-analysis.
AB  - As violence against self and others is an important outcome in the treatment of
      patients with psychosis-spectrum disorders and hostility is an important
      indicator for violence, we set out to evaluate the effects of different types of
      antipsychotic agents in reducing hostility. We performed a systematic literature
      search, which provided 18 suitable randomized studies comparing typical to
      atypical antipsychotics for at least 4 weeks in patients with psychotic
      disorders. Results showed a small (0.26) but significant effect for atypical as
      compared to typical antipsychotics, with high heterogeneity, even though the mean
      dose of typical antipsychotics was higher. This effect size remained similar when
      separately analyzing sponsored and non-sponsored studies. When differentiating
      between high and low-dose studies, the high-dose group showed a significant
      difference between typical and atypical antipsychotics whereas the low-dose group
      did not. An analysis comparing clozapine to typical antipsychotics showed a
      moderate effect size (0.415), with low heterogeneity. These results are important
      for clinicians to help their shared decision making with patients when choosing
      maintenance treatment, as next to efficacy for psychosis and tolerability, safety
      for the patient and their environment is an important outcome.

PMID- 30093699
TI  - Striatal activity correlates with stimulant-like effects of alcohol in healthy
      volunteers.
AB  - Individuals who experience greater stimulation and less sedation from alcohol are
      at increased risk for alcohol-related problems. However, little is known
      regarding the neurobiological mechanisms underlying subjective response to
      alcohol. The current study examined the degree to which alcohol-induced brain
      activation correlates with ratings of stimulation and sedation, using a within
      subjects, double-blind, placebo-controlled design. Participants (N = 34 healthy
      adults with no history of alcohol use disorder) completed three sessions: a
      calibration session to determine the duration of infusion needed to bring the
      breath alcohol to 80 mg/dl for each subject, and two counterbalanced fMRI
      sessions with placebo and alcohol administration. During the fMRI sessions,
      participants underwent 50 min scans, which included a 10 min baseline period, the
      IV infusion period needed to bring breath alcohol concentration (BrAC) to a peak
      80 mg/dl (on the alcohol session), followed by a post-peak decline period.
      Participants rated their subjective stimulation and sedation at regular intervals
      throughout the scan. A priori VOI analyses showed that the time course of
      stimulation correlated with BOLD signal in the striatum. The time course of
      sedation did not correlate with BOLD signal in any VOIs. There were no
      correlations in primary visual cortex, which served as a control. These findings
      are the first to show that alcohol effects in the striatum are linked to the
      positive, stimulant-like effects of the drug and advance our understanding of the
      neurobiological mechanisms underlying individual differences in subjective
      responses to alcohol, and more broadly, risk for alcohol use disorders.

PMID- 30093700
TI  - Author Correction: Androgen receptor is a potential novel prognostic marker and
      oncogenic target in osteosarcoma with dependence on CDK11.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30093701
TI  - Neural network identification of people hidden from view with a single-pixel,
      single-photon detector.
AB  - Light scattered from multiple surfaces can be used to retrieve information of
      hidden environments. However, full three-dimensional retrieval of an object
      hidden from view by a wall has only been achieved with scanning systems and
      requires intensive computational processing of the retrieved data. Here we use a
      non-scanning, single-photon single-pixel detector in combination with a deep
      convolutional artificial neural network: this allows us to locate the position
      and to also simultaneously provide the actual identity of a hidden person, chosen
      from a database of people (N = 3). Artificial neural networks applied to specific
      computational imaging problems can therefore enable novel imaging capabilities
      with hugely simplified hardware and processing times.

PMID- 30093702
TI  - Silkworms suppress the release of green leaf volatiles by mulberry leaves with an
      enzyme from their spinnerets.
AB  - In response to herbivory, plants emit a blend of volatile organic compounds that
      includes green leaf volatiles (GLVs) and terpenoids. These volatiles are known to
      attract natural enemies of herbivores and are therefore considered to function as
      an indirect defense. Selection should favor herbivores that are able to suppress
      these volatile emissions, and thereby make themselves less conspicuous to natural
      enemies. We tested this possibility for silkworms, which were observed to leave
      secretions from their spinnerets while feeding on mulberry leaves. When we
      ablated the spinnerets of silkworms, no secretions were observed. Leaves infested
      by intact silkworms released smaller amounts of GLVs than leaves infested by
      ablated silkworms, indicating that the spinneret secretion suppressed GLV
      production. This difference in GLV emissions was also reflected in the behavioral
      response of Zenillia dolosa (Tachinidae), a parasitoid fly of silkworms. The
      flies laid fewer eggs when exposed to the volatiles from intact silkworm-infested
      leaves than when exposed to the volatiles from ablated silkworm-infested leaves.
      We identified a novel enzyme in the secretion from the spinneret that is
      responsible for the GLV suppression. The enzyme converted 13(S)-hydroperoxy
      (9Z,11E,15Z)-octadecatrienoic acid, an intermediate in the biosynthetic pathway
      of GLVs, into its keto-derivative in a stereospecific manner. Taken together,
      this study shows that silkworms are able to feed on mulberry in a stealthy manner
      by suppressing GLV production with an enzyme in secretions of their spinnerets,
      which might be a countermeasure against induced indirect defense by mulberry
      plants.

PMID- 30093704
TI  - Feasibility and pilot studies pave the way for definitive trials.

PMID- 30093703
TI  - Validation of an algorithm to reveal the U wave in atrial fibrillation.
AB  - Major cardiac organisations recommend U wave abnormalities should be reported
      during ECG interpretation. However, U waves cannot be measured in patients with
      atrial fibrillation (AF) due to the obscuring fibrillatory wave. The aim was to
      validate a U wave measurement algorithm for AF patients. Multi-beat averaging was
      applied to ECGs of 25 patients during paroxysms of AF and the presence of U waves
      compared to those from the same patients during sinus rhythm (SR). In a further
      database of 10 long-term AF recordings, the number of beats for effective U wave
      extraction by the algorithm was calculated. U waves were revealed in all AF
      recordings and there was no significant difference between the presence of U
      waves in AF and SR (p = 0.88). U wave amplitude was significantly increased in AF
      (mean (s.d.) amplitude 55 (39) AF vs 37 (28) MUV SR, p = 0.005). The presence of
      U waves could easily be discerned when as few as 10 beats were used in the
      algorithm. The study demonstrates the validity of the algorithm to reveal U waves
      in AF recordings. The algorithm offers the potential to detect U wave
      abnormalities in patients with AF.

PMID- 30093705
TI  - Fenbendazole acts as a moderate microtubule destabilizing agent and causes cancer
      cell death by modulating multiple cellular pathways.
AB  - Drugs that are already clinically approved or experimentally tested for
      conditions other than cancer, but are found to possess previously unrecognized
      cytotoxicity towards malignant cells, may serve as fitting anti-cancer
      candidates. Methyl N-(6-phenylsulfanyl-1H benzimidazol-2-yl) carbamate
      [Fenbendazole, FZ], a benzimidazole compound, is a safe and inexpensive
      anthelmintic drug possessing an efficient anti-proliferative activity. In our
      earlier work, we reported a potent growth-inhibitory activity of FZ caused
      partially by impairment of proteasomal function. Here, we show that FZ
      demonstrates moderate affinity for mammalian tubulin and exerts cytotoxicity to
      human cancer cells at micromolar concentrations. Simultaneously, it caused
      mitochondrial translocation of p53 and effectively inhibited glucose uptake,
      expression of GLUT transporters as well as hexokinase (HK II) - a key glycolytic
      enzyme that most cancer cells thrive on. It blocked the growth of human
      xenografts in nu/nu mice model when mice were fed with the drug orally. The
      results, in conjunction with our earlier data, suggest that FZ is a new
      microtubule interfering agent that displays anti-neoplastic activity and may be
      evaluated as a potential therapeutic agent because of its effect on multiple
      cellular pathways leading to effective elimination of cancer cells.

PMID- 30093706
TI  - Significant enhancement of nitrous oxide energy yields from wastewater achieved
      by bioaugmentation with a recombinant strain of Pseudomonas aeruginosa.
AB  - Nitrous oxide (N2O) is formed during wastewater nitrogen removal processes. It is
      a strong greenhouse gas, however, if properly captured it can also be used as a
      renewable energy source. In this study, a nosZ-deficient strain of Pseudomonas
      aeruginosa was constructed. During growth under denitrifying conditions, the nosZ
      deficient strain was more highly transcribing other genes from the
      denitrification pathway (narG, nirS, and norB) than the wild-type strain. This
      strain could also convert 85% of NO2--N to N2O when it was grown with acetate
      compared to <0.6% by the wild-type strain. When a bioreactor treating synthetic
      wastewater with high NO2--N concentrations (700 mg/L) was inoculated with this
      strain, the N2O conversion efficiencies were >73% and N2O comprised 73~81% of the
      biogas being generated. The energy yield from wastewater in bioaugmented reactors
      also reached levels as high as 1260 kJ/m3. These results are significant and show
      that bioaugmentation of reactors during denitrification treatment processes with
      nosZ-deficient strains of Pseudomonas or other core denitrifying bacteria might
      be an effective way to enhance N2O recovery.

PMID- 30093708
TI  - Paradigm shifts in newborn screening?

PMID- 30093707
TI  - T cell-intrinsic IL-1R signaling licenses effector cytokine production by memory
      CD4 T cells.
AB  - Innate cytokines are critical drivers of priming and differentiation of naive CD4
      T cells, but their functions in memory T cell response are largely undefined.
      Here we show that IL-1 acts as a licensing signal to permit effector cytokine
      production by pre-committed Th1 (IFN-gamma), Th2 (IL-13, IL-4, and IL-5) and Th17
      (IL-17A, IL-17F, and IL-22) lineage cells. This licensing function of IL-1 is
      conserved across effector CD4 T cells generated by diverse immunological insults.
      IL-1R signaling stabilizes cytokine transcripts to enable productive and rapid
      effector functions. We also demonstrate that successful lineage commitment does
      not translate into productive effector functions in the absence of IL-1R
      signaling. Acute abrogation of IL-1R signaling in vivo results in reduced IL-17A
      production by intestinal Th17 cells. These results extend the role of innate
      cytokines beyond CD4 T cell priming and establish IL-1 as a licensing signal for
      memory CD4 T cell function.

PMID- 30093709
TI  - The New York pilot newborn screening program for lysosomal storage diseases:
      Report of the First 65,000 Infants.
AB  - PURPOSE: We conducted a consented pilot newborn screening (NBS) for Pompe,
      Gaucher, Niemann-Pick A/B, Fabry, and MPS 1 to assess the suitability of these
      lysosomal storage disorders (LSDs) for public health mandated screening. METHODS:
      At five participating high-birth rate, ethnically diverse New York City
      hospitals, recruiters discussed the study with postpartum parents and documented
      verbal consent. Screening on consented samples was performed using multiplexed
      tandem mass spectrometry. Screen-positive infants underwent confirmatory
      enzymology, DNA testing, and biomarker quantitation when available. Affected
      infants are being followed for clinical management and long-term outcome.
      RESULTS: Over 4 years, 65,605 infants participated, representing an overall
      consent rate of 73%. Sixty-nine infants were screen-positive. Twenty-three were
      confirmed true positives, all of whom were predicted to have late-onset
      phenotypes. Six of the 69 currently have undetermined disease status. CONCLUSION:
      Our results suggest that NBS for LSDs is much more likely to detect individuals
      at risk for late-onset disease, similar to results from other NBS programs. This
      work has demonstrated the feasibility of using a novel consented pilot NBS study
      design that can be modified to include other disorders under consideration for
      public health implementation as a means to gather critical evidence for evidence
      based NBS practices.

PMID- 30093710
TI  - Medical genetics in developing countries in the Asia-Pacific region: challenges
      and opportunities.
AB  - Advances in genetic and genomic technology changed health-care services rapidly
      in low and middle income countries (LMICs) in the Asia-Pacific region. While
      genetic services were initially focused on population-based disease prevention
      strategies, they have evolved into clinic-based and therapeutics-oriented
      service. Many LMICs struggled with these noncommunicable diseases and were
      unprepared for the needs of a clinical genetic service. The emergence of a middle
      class population, the lack of regulatory oversight, and weak capacity-building in
      medical genetics expertise and genetic counseling services led to a range of
      genetic services of variable quality with minimal ethical oversight. Some of the
      current shortcomings faced include the lack of awareness of cultural values in
      genetic health care, the variable stages of socioeconomic development and
      educational background that led to increased demand and abuse of genetics, the
      role of women in society and the crisis of gender selection, the lack of
      preventive and care services for genetic and birth defects, the issues of gene
      ethics in medicine, and the lack of understanding of some religious
      controversies. These challenges provide opportunities for both developing and
      developed nations to work together to reduce the inequalities and to ensure a
      caring, inclusive, ethical, and cost-effective genetic service in the region.

PMID- 30093713
TI  - Frequency of vitamin K oxidoreductase complex subunit-1 (VKORC1) polymorphisms
      and warfarin dose management in patients with venous thromboembolism.
AB  - Warfarin works by inhibiting VKORC1, so polymorphisms of this gene modify the
      required drug dose. The aim of this study is to examine the relation between
      therapeutic weekly dose of warfarin and C1173T/G1639A polymorphism of VKORC1 in
      patients with VTE. Seventy-five patients with VTE were enrolled. Weekly warfarin
      doses and time (day) to reach therapeutic INR were evaluated retrospectively
      along with VKORC1-C1173T and G1639A alleles. The mean weekly warfarin dose was
      lower and time to reach therapeutic INR was shorter in homozygote alleles (AA and
      TT) (p < 0.05). The multivariate regression model was produced, R2 = 0.05% for
      age (p = 0.04), R2 = 6% for VKORC1 (p = 0.03), the model for estimating warfarin
      dose R2 = 17% (p > 0.05). In particular, patients who need overdose of warfarin
      or whose bleeding score is high, study of these polymorphisms can be considered.

PMID- 30093712
TI  - Retention and losses of ultraviolet-sensitive visual pigments in bats.
AB  - Ultraviolet (UV)-sensitive visual pigment and its corresponding ability for UV
      vision was retained in early mammals from their common ancestry with sauropsids.
      Subsequently, UV-sensitive pigments, encoded by the short wavelength-sensitive 1
      (SWS1) opsin gene, were converted to violet sensitivity or have lost function in
      multiple lineages during the diversification of mammals. However, many mammalian
      species, including most bats, are suggested to retain a UV-sensitive pigment.
      Notably, some cave-dwelling fruit bats and high duty cycle echolocating bats have
      lost their SWS1 genes, which are proposed to be due to their roosting ecology and
      as a sensory trade-off between vision and echolocation, respectively. Here, we
      sequenced SWS1 genes from ecologically diverse bats and found that this gene is
      also non-functional in both common vampire bat (Desmodus rotundus) and white
      winged vampire bat (Diaemus youngi). Apart from species with pesudogenes, our
      evolutionary and functional studies demonstrate that the SWS1 pigment of bats are
      UV-sensitive and well-conserved since their common ancestor, suggesting an
      important role across major ecological types. Given the constrained function of
      SWS1 pigments in these bats, why some other species, such as vampire bats, have
      lost this gene is even more interesting and needs further investigation.

PMID- 30093714
TI  - Polymorphisms in CEP68 gene associated with risk of immediate selective reactions
      to non-steroidal anti-inflammatory drugs.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are the main triggers of drug
      hypersensitivity reactions. Such reactions can be pharmacologically or
      immunologically mediated, but in both cases individual susceptibility can be
      influenced by genetic factors. Polymorphisms in centrosomal protein of 68 kDa
      (CEP68) have been associated with pharmacologically mediated NSAIDs reactions.
      Here, we evaluated this gene in immunologically mediated single-NSAID-induced
      urticaria/angioedema or anaphylaxis (SNIUAA) by analyzing 52 single nucleotide
      polymorphisms in CEP68 in 176 patients and 363 NSAIDs-tolerant controls. Two
      intronic variants (rs2241160 and rs2241161) were significantly associated with an
      increased risk of SNIUAA, suggesting CEP68 to be a key player in both types of
      NSAIDs hypersensitivity. However, we found no overlap with genetic variants
      previously associated with pharmacologically mediated hypersensitivity, pointing
      to a complex role for this gene and its potential use in the development of
      biomarkers of clinical utility to diagnose patients at risk of these reactions
      and to differentiate entities.

PMID- 30093715
TI  - Cross-ethnicity tagging SNPs for HLA alleles associated with adverse drug
      reaction.
AB  - Reduction of adverse drug reaction (ADR) incidence through screening of
      predisposing human leucocyte antigen (HLA) alleles is a promising approach for
      many widely used drugs. However, application of these associations has been
      limited by the cost burden of HLA genotyping. Use of single nucleotide
      polymorphisms (SNPs) that can approximate ('tag') HLA alleles of interest has
      been proposed as a cost-effective and simple alternative to conventional
      genotyping. However, most reported SNP tags have not been validated and there is
      concern regarding clinical utility of this approach due to tagging inconsistency
      across different populations. We assess the ability of 67 previously reported and
      378 novel tagging SNPs, identified here in 5 HLA reference panels, to tag 15 ADR
      associated HLA alleles in a panel of 955 ethnically diverse samples. Tags for 8
      HLA alleles of interest were identified with 100% sensitivity and >95%
      specificity. These SNPs may act as a reliable genotyping approach for the routine
      screening of patients, without the need to account for patient ethnicity.

PMID- 30093716
TI  - Identification of influential spreaders in complex networks using HybridRank
      algorithm.
AB  - Identifying the influential spreaders in complex networks is crucial to
      understand who is responsible for the spreading processes and the influence
      maximization through networks. Targeting these influential spreaders is
      significant for designing strategies for accelerating the propagation of
      information that is useful for various applications, such as viral marketing
      applications or blocking the diffusion of annoying information (spreading of
      viruses, rumors, online negative behaviors, and cyberbullying). Existing methods
      such as local centrality measures like degree centrality are less effective, and
      global measures like closeness and betweenness centrality could better identify
      influential spreaders but they have some limitations. In this paper, we propose
      the HybridRank algorithm using a new hybrid centrality measure for detecting a
      set of influential spreaders using the topological features of the network. We
      use the SIR spreading model for simulating the spreading processes in networks to
      evaluate the performance of our algorithm. Empirical experiments are conducted on
      real and artificial networks, and the results show that the spreaders identified
      by our approach are more influential than several benchmarks.

PMID- 30093711
TI  - The landscape of epilepsy-related GATOR1 variants.
AB  - PURPOSE: To define the phenotypic and mutational spectrum of epilepsies related
      to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative
      regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of
      73 novel probands (familial and sporadic) with epilepsy-related variants in
      GATOR1-encoding genes and proposed new guidelines for clinical interpretation of
      GATOR1 variants. RESULTS: The GATOR1 seizure phenotype consisted mostly in focal
      seizures (e.g., hypermotor or frontal lobe seizures in 50%), with a mean age at
      onset of 4.4 years, often sleep-related and drug-resistant (54%), and associated
      with focal cortical dysplasia (20%). Infantile spasms were reported in 10% of the
      probands. Sudden unexpected death in epilepsy (SUDEP) occurred in 10% of the
      families. Novel classification framework of all 140 epilepsy-related GATOR1
      variants (including the variants of this study) revealed that 68% are loss-of
      function pathogenic, 14% are likely pathogenic, 15% are variants of uncertain
      significance and 3% are likely benign. CONCLUSION: Our data emphasize the
      increasingly important role of GATOR1 genes in the pathogenesis of focal
      epilepsies (>180 probands to date). The GATOR1 phenotypic spectrum ranges from
      sporadic early-onset epilepsies with cognitive impairment comorbidities to
      familial focal epilepsies, and SUDEP.

PMID- 30093717
TI  - Differential association of ezetimibe-simvastatin combination with major adverse
      cardiovascular events in patients with or without diabetes: a retrospective
      propensity score-matched cohort study.
AB  - Clinical trials suggested that the benefits of ezetimibe-statin combination
      therapy on major adverse cardiovascular events (MACE) might be greater in
      patients with diabetes. We aimed to investigate the differential association of
      ezetimibe-statin combination with incident MACE by presence of diabetes. In this
      retrospective cohort study, subjects treated with simvastatin 20 mg plus
      ezetimibe 10 mg (S + E) or simvastatin 20 mg alone (S) between 2005 and 2015 were
      1:1 matched using propensity score as stratified by diabetes. Primary outcome was
      newly-developed MACE composed of cardiovascular death, ACS, coronary
      revascularization, or non-hemorrhagic stroke. During 5,077 and 12,439 person
      years, the incidence rates of MACE were 24.9, 20.1, 35.3, and 22.8/1000 person
      years among no diabetes S, no diabetes S + E, diabetes S, and diabetes S + E,
      respectively. Relative to no diabetes S, adjusted HR (aHR) for MACE in diabetes S
      was 1.23 (p = 0.086), whereas S + E was associated with a lower risk of MACE in
      both non-diabetic patients (aHR 0.76, p = 0.047) and diabetic patients (aHR 0.60,
      p = 0.007) with significant difference (relative excess risk due to interaction =
      -0.39, p = 0.044). In conclusion, reduction of MACE risk associated with
      ezetimibe plus simvastatin therapy relative to simvastatin alone was greater in
      patients with diabetes than in patients without diabetes.

PMID- 30093718
TI  - A nuclear-encoded protein, mTERF6, mediates transcription termination of rpoA
      polycistron for plastid-encoded RNA polymerase-dependent chloroplast gene
      expression and chloroplast development.
AB  - The expression of plastid genes is regulated by two types of DNA-dependent RNA
      polymerases, plastid-encoded RNA polymerase (PEP) and nuclear-encoded RNA
      polymerase (NEP). The plastid rpoA polycistron encodes a series of essential
      chloroplast ribosome subunits and a core subunit of PEP. Despite the functional
      importance, little is known about the regulation of rpoA polycistron. In this
      work, we show that mTERF6 directly associates with a 3'-end sequence of rpoA
      polycistron in vitro and in vivo, and that absence of mTERF6 promotes read
      through transcription at this site, indicating that mTERF6 acts as a factor
      required for termination of plastid genes' transcription in vivo. In addition,
      the transcriptions of some essential ribosome subunits encoded by rpoA
      polycistron and PEP-dependent plastid genes are reduced in the mterf6 knockout
      mutant. RpoA, a PEP core subunit, accumulates to about 50% that of the wild type
      in the mutant, where early chloroplast development is impaired. Overall, our
      functional analyses of mTERF6 provide evidence that it is more likely a factor
      required for transcription termination of rpoA polycistron, which is essential
      for chloroplast gene expression and chloroplast development.

PMID- 30093720
TI  - Bundles of Brain Microtubules Generate Electrical Oscillations.
AB  - Microtubules (MTs) are long cylindrical structures of the cytoskeleton that
      control cell division, intracellular transport, and the shape of cells. MTs also
      form bundles, which are particularly prominent in neurons, where they help define
      axons and dendrites. MTs are bio-electrochemical transistors that form nonlinear
      electrical transmission lines. However, the electrical properties of most MT
      structures remain largely unknown. Here we show that bundles of brain MTs
      spontaneously generate electrical oscillations and bursts of electrical activity
      similar to action potentials. Under intracellular-like conditions, voltage
      clamped MT bundles displayed electrical oscillations with a prominent fundamental
      frequency at 39 Hz that progressed through various periodic regimes. The
      electrical oscillations represented, in average, a 258% change in the ionic
      conductance of the MT structures. Interestingly, voltage-clamped membrane
      permeabilized neurites of cultured mouse hippocampal neurons were also capable of
      both, generating electrical oscillations, and conducting the electrical signals
      along the length of the structure. Our findings indicate that electrical
      oscillations are an intrinsic property of brain MT bundles, which may have
      important implications in the control of various neuronal functions, including
      the gating and regulation of cytoskeleton-regulated excitable ion channels and
      electrical activity that may aid and extend to higher brain functions such as
      memory and consciousness.

PMID- 30093719
TI  - Metabolomic changes in the mouse retina after optic nerve injury.
AB  - In glaucoma, although axonal injury drives retinal ganglion cell (RGC) death,
      little is known about the underlying pathomechanisms. To provide new mechanistic
      insights and identify new biomarkers, we combined latest non-targeting
      metabolomics analyses to profile altered metabolites in the mouse whole retina 2,
      4, and 7 days after optic nerve crush (NC). Ultra-high-performance liquid
      chromatography quadrupole time-of-flight mass spectrometry and liquid
      chromatography Fourier transform mass spectrometry covering wide spectrum of
      metabolites in combination highlighted 30 metabolites that changed its
      concentration after NC. The analysis displayed similar changes for purine
      nucleotide and glutathione as reported previously in another animal model of
      axonal injury and detected multiple metabolites that increased after the injury.
      After studying the specificity of the identified metabolites to RGCs in
      histological sections using imaging mass spectrometry, two metabolites, i.e., L
      acetylcarnitine and phosphatidylcholine were increased not only preceding the
      peak of RGC death in the whole retina but also at the RGC layer (2.3-fold and 1.2
      fold, respectively). These phospholipids propose novel mechanisms of RGC death
      and may serve as early biomarkers of axonal injury. The combinatory metabolomics
      analyses promise to illuminate pathomechanisms, reveal biomarkers, and allow the
      discovery of new therapeutic targets of glaucoma.

PMID- 30093723
TI  - FOXP2 tells a cautionary tale.

PMID- 30093724
TI  - Lessons from 1 million genomes.

PMID- 30093722
TI  - The impacts of delivery mode on infant's oral microflora.
AB  - This study investigated the effects of different delivery modes on oral
      microflora in healthy newborns immediately post-partum, and provided evidence for
      microbial colonization disruption induced by medical procedures. Eighteen infants
      delivered by cesarean section and 74 by vaginal delivery were included in the
      study. High-throughput sequencing of 16S bacterial rRNA was performed on oral
      samples collected immediately after birth. All data were analyzed using
      bioinformatics approaches. Our results indicated that different oral bacteria
      were found between infants delivered by cesarean section compared to vaginal
      delivery group. Lactobacillus, Prevotella and Gardnerella were the most abundant
      genera in the vaginal group, while Petrimonas, Bacteroides, Desulfovibrio,
      Pseudomonas, Staphylococcus, Tepidmicrobium, VadinCA02, and Bifidobacterium were
      dominant bacteria in the cesarean section (C-section) group. Furthermore,
      bacteria isolated from 27 vaginally-delivered infants were not clustered into the
      vaginal group. Most of them spent more than 24 hours in the delivery room and
      this led to repeated sterilization procedures. We hypothesized that repeated
      sterilization might have influenced oral microflora in those cases. To conclude,
      this study suggested that different modes of birth delivery affect oral
      microflora in healthy infants. In addition, attention shall be paid to the
      clinical practice of repeated sterilization of the vulva that possibly obstructs
      the colonization of vaginal bacterial.

PMID- 30093721
TI  - Functional near-infrared spectroscopy for monitoring macaque cerebral motor
      activity during voluntary movements without head fixation.
AB  - We developed an fNIRS system for monitoring macaque cerebral motor activity
      during voluntary movements without head fixation. fNIRS data at 27 channels in
      7.5 mm spatial interval were calibrated by simulating light propagation through
      the macaque cranial tissues. The subject was instructed to repeatedly (75 times)
      retrieve a food pellet with alternating left or right hands from a food well for
      each session. We detected significant increases in oxygenated hemoglobin (Hb) and
      decrease in deoxygenated Hb in the primary motor area (M1) contralateral to the
      hand used. In more rostral and ventral regions in both hemispheres, the
      hemodynamic similarly changed regardless of used hand. Direct feeding to the
      mouth eliminated activity in the hand M1 whereas that at bilateral ventral
      regions (mouth M1 area) remained. Statistical analyses for the hemodynamics
      between left/right-hand use revealed the location of each hand M1 in either
      hemisphere. In these regions, the maximum amplitude and time of the maximum
      amplitude in the hemodynamic response evoked by food retrieval were highly
      correlated with the time associated with food retrieval. We could assign each
      channel to an appropriate functional motor area, providing proof of principle for
      future studies involving brain damage models in freely moving macaque monkeys.

PMID- 30093725
TI  - Perturbation to the nitrogen cycle during rapid Early Eocene global warming.
AB  - The degree to which ocean deoxygenation will alter the function of marine
      communities remains unclear but may be best constrained by detailed study of
      intervals of rapid warming in the geologic past. The Paleocene-Eocene Thermal
      Maximum (PETM) was an interval of rapid warming that was the result of increasing
      contents of greenhouse gases in the atmosphere that had wide ranging effects on
      ecosystems globally. Here, we present stable nitrogen isotope data from the
      Eastern Peri-Tethys Ocean that record a significant transition in the nitrogen
      cycle. At the initiation of the PETM, the nitrogen isotopic composition of
      sediments decreased by ~60/00 to as low as -3.40/00, signaling reorganization of
      the marine nitrogen cycle. Warming, changes in ocean circulation, and
      deoxygenation caused a transition to nitrogen cycle to conditions that were most
      similar to those experienced during Oceanic Anoxic Events of the Mesozoic.

PMID- 30093726
TI  - Lysyl hydroxylases are transcription targets for GATA3 driving lung cancer cell
      metastasis.
AB  - Metastasis associates with late stages of lung cancer progression and remains the
      main cause of patient death due to the lack of clinically effective therapeutics.
      Here we report that the transcription factor GATA3 and its co-factor FOG2
      commonly promote the expression of the lysyl hydroxylase (LH) family members,
      including LH2 and LH3, which in turn drive lung adenocarcinoma cell migration,
      invasion, and metastasis. We show evidence that both LH2 and LH3 are direct
      transcription targets for GATA3. Knockdown of either LH2 or LH3 suppresses
      migration and invasion; on the contrary, forced expression of LH2 or LH3 promotes
      growth and migration, suggesting that the two LHs exert redundant oncogenic
      functions. Importantly, re-expression of LH2 is sufficient to restore the
      metastatic capacity of GATA3-depleted cells, suggesting a role for LHs as the
      downstream mediators of GATA3. Collectively, our data reveal a pro-metastatic
      GATA3-LHs axis for lung cancer, supporting the notion that targeting LHs may be
      useful for treating lung cancer.

PMID- 30093728
TI  - New aspects of longitudinal instabilities in electron storage rings.
AB  - Novel features of the longitudinal instability of a single electron bunch
      circulating in a low-emittance electron storage ring are discussed. Measurements
      and numerical simulations, performed both in time and frequency domain, show a
      non-monotonic increase of the electron beam energy spread as a function of single
      bunch current, characterized by the presence of local minima and maxima, where a
      local minimum of the energy spread is interpreted as a higher-order microwave
      instability threshold. It is also shown that thresholds related to the same zero
      intensity bunch length depend linearly on the accelerating radio frequency
      voltage. The observed intensity-dependent features of the energy spread,
      confirmed by measurements with two independent diagnostics methods, i.e.
      horizontal beam profile measurements by a synchrotron light monitor and photon
      energy spectrum measurements of undulator radiation, are given a theoretical
      interpretation by applying a novel eigenvalue analysis based on the linearized
      Vlasov equation.

PMID- 30093729
TI  - Publisher Correction: Global characterization of T cells in non-small-cell lung
      cancer by single-cell sequencing.
AB  - In the version of this article originally published, the P statistic described in
      Fig. 3d was incorrect. It was described as "P < 22 * 10-16". It should have been
      "P < 2.2 * 10-16". Also, the "CD8+ Treg" label in Fig. 4f was incorrect. It
      should have been "CD4+ Treg". The errors have been corrected in the HTML and PDF
      versions of this article.

PMID- 30093727
TI  - Mechanisms of wheat (Triticum aestivum) grain storage proteins in response to
      nitrogen application and its impacts on processing quality.
AB  - Basis for the effects of nitrogen (N) on wheat grain storage proteins (GSPs) and
      on the establishment of processing quality are far from clear. The response of
      GSPs and processing quality parameters to four N levels of four common wheat
      cultivars were investigated at two sites over two growing seasons. Except gluten
      index (GI), processing quality parameters as well as GSPs quantities were
      remarkably improved by increasing N level. N level explained 4.2~59.2% and
      10.4~80.0% variability in GSPs fractions and processing quality parameters,
      respectively. The amount of N remobilized from vegetative organs except spike was
      significantly increased when enhancing N application. GSPs fractions and
      processing quality parameters except GI were only highly and positively
      correlated with the amount of N remobilized from stem with sheath. N
      reassimilation in grain was remarkably strengthened by the elevated activity and
      expression level of glutamine synthetase. Transcriptome analysis showed the
      molecular mechanism of seeds in response to N levels during 10~35 days post
      anthesis. Collectively, we provided comprehensive understanding of N-responding
      mechanisms with respect to wheat processing quality from N source to GSPs
      biosynthesis at the agronomic, physiological and molecular levels, and screened
      candidate genes for quality breeding.

PMID- 30093730
TI  - Author Correction: Targeting wild-type KRAS-amplified gastroesophageal cancer
      through combined MEK and SHP2 inhibition.
AB  - In the Supplementary Information originally published with this article, a lane
      was missing in the beta-actin blot in Supplementary Fig. 2. The lane has been
      added. The error has been corrected in the Supplementary Information associated
      with this article.

PMID- 30093731
TI  - Publisher Correction: Molecular phenomics and metagenomics of hepatic steatosis
      in non-diabetic obese women.
AB  - In the version of this article originally published, the received date was
      missing. It should have been listed as 2 January 2018. The error has been
      corrected in the HTML and PDF versions of this article.

PMID- 30093734
TI  - Index Volume 80 (2013).

PMID- 30093733
TI  - Crystallization of Tyrian Purple (6,6'-Dibromoindigo) Thin Films: The Impact of
      Substrate Surface Modifications.
AB  - The pigment 6,6'-dibromoindigo (Tyrian purple) shows strong intermolecular
      hydrogen bonds and the film formation is, therefore, expected to be influenced by
      the polar character of the substrate surface. Thin films of Tyrian purple were
      prepared by physical vapor deposition on a variety of substrates with different
      surface energies: from highly polar silicon dioxide surfaces to hydrophobic
      polymer surfaces. The crystallographic properties were investigated by X-ray
      diffraction techniques such as X-ray reflectivity and grazing incidence X-ray
      diffraction. In all cases, crystallites with "standing" molecules relative to the
      substrate surface were observed independently of the substrate surface energy. In
      the case of polymer surfaces, additional crystallites are formed containing
      "lying" molecules with their aromatic planes parallel to the substrate surface.
      Small differences in the crystallographic lattice constants were observed as a
      function of substrate surface energy, the corresponding small changes in the
      molecular packing are explained by a variation of the hydrogen bond geometries.
      This work reveals that despite the limited influence of the surface energy on the
      molecular orientation, the crystalline packing of Tyrian purple within thin films
      is altered and slightly different structures form.

PMID- 30093735
TI  - On the Specification of Upward-Propagating Tides for ICON Science Investigations.
AB  - The National Center for Atmospheric Research (NCAR) Thermosphere Ionosphere
      Electrodynamics General Circulation Model (TIEGCM) will provide a physics-based
      context for the interpretation of ICON measurements. To optimize the realism of
      the model simulations, ICON wind and temperature measurements near the ~97 km
      lower boundary of the TIEGCM will be used to specify the upward-propagating tidal
      spectrum at this altitude. This will be done by fitting a set of basis functions
      called Hough Mode Extensions (HMEs) to 27-day mean tidal winds and temperatures
      between 90 and 105 km altitude and between 12 degrees S and 42 degrees N latitude
      on a day-by-day basis. The current paper assesses the veracity of the HME fitting
      methodology given the restricted latitude sampling and the UT-longitude sampling
      afforded by the MIGHTI instrument viewing from the ICON satellite, which will be
      in a circular 27 degrees  inclination orbit. These issues are investigated using
      the output from a reanalysis-driven global circulation model, which contains
      realistic variability of the important tidal components, as a mock data set. ICON
      sampling of the model reveals that the 27-day mean diurnal and semidiurnal tidal
      components replicate well the 27-day mean tidal components obtained from full
      synoptic sampling of the model, but the terdiurnal tidal components are not
      faithfully reproduced. It is also demonstrated that reconstructed tidal
      components based on HME fitting to the model tides between 12 degrees S and 42
      degrees N latitude provide good approximations to the major tidal components
      expected to be encountered during the ICON mission. This is because the
      constraints provided by fitting both winds and temperatures over the 90-105 km
      height range are adequate to offset the restricted sampling in latitude. The
      boundary conditions provided by the methodology described herein will greatly
      enhance the ability of the TIEGCM to provide a physical framework for
      interpreting atmosphere-ionosphere coupling in ICON observations due to
      atmospheric tides.

PMID- 30093732
TI  - Diabetes induces fibrotic changes in the lung through the activation of TGF-beta
      signaling pathways.
AB  - In the long term, diabetes profoundly affects multiple organs, such as the
      kidney, heart, brain, liver, and eyes. The gradual loss of function in these
      vital organs contributes to mortality. Nonetheless, the effects of diabetes on
      the lung tissue are not well understood. Clinical and experimental data from our
      studies revealed that diabetes induces inflammatory and fibrotic changes in the
      lung. These changes were mediated by TGF-beta-activated epithelial-to-mesenchymal
      transition (EMT) signaling pathways. Our studies also found that glucose
      restriction promoted mesenchymal-to-epithelial transition (MET) and substantially
      reversed inflammatory and fibrotic changes, suggesting that diabetes-induced EMT
      was mediated in part by the effects of hyperglycemia. Additionally, the
      persistent exposure of diabetic cells to high glucose concentrations (25 mM)
      promoted the upregulation of caveolin-1, N-cadherin, SIRT3, SIRT7 and lactate
      levels, suggesting that long-term diabetes may promote cell proliferation. Taken
      together, our results demonstrate for the first time that diabetes induces
      fibrotic changes in the lung via TGF-beta1-activated EMT pathways and that
      elevated SMAD7 partially protects the lung during the initial stages of diabetes.
      These findings have implications for the management of patients with diabetes.

PMID- 30093736
TI  - Injustice in Mobile Leisure: A Conceptual Exploration of Pokemon Go.
AB  - In augmented reality, video games and the physical world converge as individuals
      participate in digital leisure overlaid on physical spaces. In Pokemon Go, game
      play in the physical world is impacted by constraints that limit access and play
      of marginalized groups. Global popularity of Pokemon Go created an opportunity to
      explore experiences of marginalized groups participating in augmented reality
      game play. Grey literature surrounding Pokemon Go is rich with accounts of
      constraints experienced by marginalized groups, particularly individuals self
      identifying as White women, Black women, or Black men. Their experiences with
      Pokemon Go illustrate the need for social justice in digital leisure. Because the
      lifespan of mobile applications is limited, the gradual process from research to
      social change may be insufficient in addressing ever evolving digital platforms.
      Researchers need to strategically work with industry partners to identify needs
      for social justice during the planning and designing stages.

PMID- 30093738
TI  - Involuntary Hospitalization: The Conflict Zone of Psychiatry and Law (Revisiting
      Section 19 of Mental Health Act 1987).

PMID- 30093737
TI  - Nonparametric Adjustment for Measurement Error in Time-to-Event Data: Application
      to Risk Prediction Models.
AB  - Mismeasured time to event data used as a predictor in risk prediction models will
      lead to inaccurate predictions. This arises in the context of self-reported
      family history, a time to event predictor often measured with error, used in
      Mendelian risk prediction models. Using validation data, we propose a method to
      adjust for this type of error. We estimate the measurement error process using a
      nonparametric smoothed Kaplan-Meier estimator, and use Monte Carlo integration to
      implement the adjustment. We apply our method to simulated data in the context of
      both Mendelian and multivariate survival prediction models. Simulations are
      evaluated using measures of mean squared error of prediction (MSEP), area under
      the response operating characteristics curve (ROC-AUC), and the ratio of observed
      to expected number of events. These results show that our method mitigates the
      effects of measurement error mainly by improving calibration and total accuracy.
      We illustrate our method in the context of Mendelian risk prediction models
      focusing on misreporting of breast cancer, fitting the measurement error model on
      data from the University of California at Irvine, and applying our method to
      counselees from the Cancer Genetics Network. We show that our method improves
      overall calibration, especially in low risk deciles.

PMID- 30093739
TI  - How do Our Patients Respond to the Concept of Psychiatric Advance Directives? An
      Exploratory Study From India.
AB  - Background: Psychiatric advance directives have been incorporated in the Mental
      Health Care Act 2017 despite strong concerns about their feasibility and utility
      in the Indian patient population. Data on its utility in India is very scarce.
      Aims: To determine the possible treatment options our clients make as a part of
      psychiatric advance directives. Materials and Methods: Fifty consecutive
      individuals with severe mental illness were interviewed using a self-designed
      semi-structured tool to find out the possible choices they make as part of
      advance directives and the factors affecting their choices. Results: About 10% of
      the participants failed to understand the concept of advance directives. Of those
      who understood, 89% were willing to make advance directives, 15% refused future
      hospitalizations, 47% refused future electroconvulsive therapies (ECTs), and 62%
      refused physical restraints in future. Conclusion: The majority of the
      participants agreed to make advance directives. The majority of those who agreed
      to make advance directives refused to undergo ECTs and physical restraints in
      future episodes of illness. Approximately 10% of the patients could not
      understand the concept of advance directives.

PMID- 30093740
TI  - Cognitive Functions among Recently Detoxified Patients with Alcohol Dependence
      and Their Association with Motivational State to Quit.
AB  - Context: Cognitive impairments are common among patients with alcohol dependence.
      It may involve frontal executive dysfunction, global cognitive impairments, or
      both. Motivation to quit alcohol involves recognition of alcohol use as a
      problem. This ability may be construed as a cognitive symptom. Aims: The aim is
      to study the frequency of cognitive dysfunction among patients with alcohol
      dependence and to study the association between cognitive dysfunction and the
      motivation to quit alcohol. Materials and Methods: Fifty-six adult males with
      alcohol dependence (International Classification of Diseases-10) who had
      completed a course of detoxification and who did not have active withdrawal
      symptoms or acute medical illnesses were recruited for this study. Their
      cognitive functions were tested using the Montreal Cognitive Assessment (MoCA)
      and Frontal Assessment Battery (FAB). Their motivation levels were assessed using
      the Stages of Change Readiness and Treatment Eagerness Scale. Clinical details
      were collected using a semi-structured pro forma. Results: Global cognitive
      impairment (MoCA < 26) was seen in 81% and frontal executive dysfunction (FAB <
      12) in 16% of patients. Higher MoCA and FAB scores correlated with better
      education, while lower FAB scores correlated with higher age. The 14 patients
      (25%) with good motivation did not differ in age, education, years of dependence,
      or MoCA or FAB scores from poorly motivated patients. FAB scores, but not MoCA,
      were associated with poor motivation. All nine patients with FAB < 12 were poorly
      motivated to quit alcohol; likelihood score = 5.731, P = 0.017. Conclusions: Four
      fifths of patients with alcohol dependence had global cognitive impairments after
      the detoxification period. One-sixth had frontal executive dysfunction. Cognitive
      functions were not significantly correlated with the duration of dependence.
      Presence of frontal executive dysfunction was associated with almost six times
      likelihood that the patient will be poorly motivated to quit alcohol.

PMID- 30093741
TI  - Relationship between Craving and Early Relapse in Alcohol Dependence: A Short
      Term Follow-up Study.
AB  - Background: The role of craving in alcohol dependence and its relationship with
      relapse has been studied widely in the past decade. The present study was
      undertaken to assess the role of craving in short-term relapse of patients
      seeking treatment for alcohol dependence and changes in craving score at the end
      of detoxification and at follow-up. Materials and Methods: A total of 34 male
      individuals with alcohol dependence (excluding comorbid drug dependence, organic
      or psychiatric disorder), after detoxification and discharge, consented. No
      anticraving medicine, aversive or psychotherapy, was advised. They were diagnosed
      on the International Statistical Classification of Diseases-10 using Diagnostic
      Interview for Genetic Studies. Severity of Alcohol Dependence Questionnaire
      (SADQ) and Clinical Institute Withdrawal Assessment Scale-Alcohol-Revised (CIWA
      AR) were administered at the time of admission. Penn Alcohol Craving Scale (PACS)
      was applied at the time of discharge and follow-up to measure craving for
      alcohol. Results: Out of a total of thirty patients analyzed after dropout, 21
      relapsed at the end of 1 month. On comparing PACS scores between relapsed and
      nonrelapsed patients, the difference was significant at both time points, i.e.,
      at discharge and follow-up (t = 4.15, P < 0.0001 and t = 4.01, P < 0.001,
      respectively). In the total sample, SADQ and CIWA-AR scores were positively
      correlated (r = 0.47, P = 0.009). PACS at discharge was compared with PACS at
      follow-up, of which the correlation was high (r = 0.832, P < 0.0001). Conclusion:
      Craving seems to be a main factor related to relapse. Its measurement with PACS
      can be a useful tool to predict subsequent drinking and to identify individual
      risk for relapse during treatment.

PMID- 30093742
TI  - Experience of Domestic Violence and Psychological Morbidity in Spouses of Alcohol
      Dependent Males.
AB  - Background: Prevalence of both domestic violence (DV) and alcohol use is reported
      to be high in Kerala. The prevalence of DV and psychological morbidity in spouses
      of alcohol-dependent males has not been studied objectively. Methods: This cross
      sectional study was undertaken to study the occurrence of DV and psychological
      morbidity-major depressive disorder (MDD), anxiety disorders, and adjustment
      disorders-in spouses of alcohol-dependent males attending the de-addiction center
      of a tertiary care hospital in South India. Sixty consecutive cases, aged 18-55
      years, were recruited after getting informed consent. They were assessed using
      Domestic Violence Questionnaire (DVQ), Mini International Neuropsychiatric
      Interview Schedule, and a questionnaire to assess adjustment disorder. The
      association of DV with psychological morbidities was also studied. Results: DV
      was reported by 41 (68.3%, 95% confidence interval [CI] = 55.0-79.7) cases. At
      least one psychiatric morbidity was observed in 51 (85.0%, 95% CI = 72.9-92.5)
      cases-MDD in 15 (25.0%, 95% CI = 15.1-38.1), anxiety disorders in 6 (10%, 95% CI
      = 4.1-21.2), and adjustment disorder in 32 (53.3%, 95% CI = 40.1-66.1) cases
      each. No statistically significant association was observed between DV and any of
      the psychiatric disorders. However, DVQ scores showed significant correlation
      with years of marriage (Pearson's r = 0.268, P < 0.05) and with stressful life
      events over the past 1 year (Pearson's r = 0.424, P < 0.05). Conclusions: High
      rates of DV and psychological morbidity were seen in spouses of alcohol-dependent
      males.

PMID- 30093743
TI  - Quality of Life and Explanatory Models of Illness in Patients with Schizophrenia.
AB  - Background: Patients with schizophrenia hold a variety of explanatory models of
      illness that influence different aspects of their life including their
      understanding of the disease, ability to cope and sense of well-being. Aim: To
      study the association of explanatory models and quality of life in patients with
      schizophrenia. Materials and Methods: One hundred and thirty consecutive patients
      with schizophrenia attending a psychiatric outpatient clinic were recruited in
      the study and administered the Positive and Negative Symptom Scale (PANSS), the
      modified Short Explanatory Model Interview (SEMI) and the World Health
      Organization Quality of Life-BREF (WHOQOL-BREF) Scale to assess severity of
      psychosis, explanatory models of illness, and quality of life. Sociodemographic
      and clinical details of patients were also recorded. Standard bivariate and
      multivariable statistics were employed. Results: Higher quality of life scores
      were associated with better socioeconomic conditions and lower scores on negative
      and general psychopathology subscales of PANSS. Quality-of-life scores were
      significantly higher in patients who did not perceive their illness to have
      negative effects on the different domains of their functioning. Conclusion:
      Explanatory models of illness are associated with perceived quality of life in
      patients with schizophrenia. There is a need to focus on attitudes, perceptions
      and functioning, rather than symptom reduction alone, to enhance the quality of
      life in schizophrenia.

PMID- 30093744
TI  - A Prospective Study to Evaluate the Effect of CYP2D6 Polymorphism on Plasma level
      of Risperidone and its Metabolite in North Indian Patients with Schizophrenia.
AB  - Background: Risperidone is one of commonly utilized antipsychotic in clinical
      practice. Various metabolizing enzymes effect the plasma levels of risperidone
      and its active metabolite and thus its clinical efficacy. So, we attempted to
      evaluate the relationship between CYP2D6*10 (rs1065852) and CYP2D6*4 (rs3892097)
      gene polymorphism and the plasma concentration of risperidone and its metabolite
      in patients with schizophrenia. Methodology: It was a 12-week prospective study
      carried out in patients diagnosed with schizophrenia. The dose of risperidone was
      increased weekly by 1 mg and rating of psychopathology was done using Positive
      and Negative Syndrome Scale (PANSS). Quantification of plasma level of
      risperidone and 9-hydroxyrisperidone was carried out at week 6 and 12 of
      treatment. The *4 and *10 alleles of CYP2D6 were genotyped and their effect on
      metabolism of risperidone was assessed. Results: The number of CYP2D6*4 alleles
      affected the plasma levels of risperidone, 9-hydroxyrisperidone at 6 weeks of
      treatment but not at 12 weeks. On the other hand, the number of mutated alleles
      for CYP2D6*10 influenced the dose corrected plasma concentration of risperidone
      and active moiety at 12 weeks of treatment. The ratio of plasma concentration of
      risperidone and 9-hydroxyrisperidone was more than one in all study participants,
      thus, suggesting that they were poor metabolizers of risperidone. Conclusion: The
      polymorphism of CYP2D6*10 affects the steady state plasma concentration of
      risperidone in Indian patients with schizophrenia.

PMID- 30093745
TI  - Screening for Mental Health Disorders among Pregnant Women Availing Antenatal
      Care at a Government Maternity Hospital in Bengaluru City.
AB  - Introduction: Antepartum anxiety and depression are two of the most common risk
      factors for the development of postpartum depression. Women are at a higher risk
      of developing depression and suffering from mental disorders during pregnancy and
      the postnatal period. Psychopathological symptoms during pregnancy have
      physiological consequences for the fetus, such as impaired blood flow leading to
      low birth weight, as well as cognitive delay and behavioral problems. Objectives:
      To screen antenatal women for common mental health disorders and to determine the
      factors associated with mental health disorders during pregnancy. Methods: A
      cross-sectional study among 208 pregnant mothers in the third trimester attending
      the antenatal clinic at a Government Maternity Home in a low-income urban area of
      Bengaluru was conducted using clinical interview schedule-revised (CIS-R)
      questionnaire as a screening tool for detecting the presence of mental morbidity.
      Data collected were analyzed using SPSS version 16. Results: In the study
      population, 12 (5.8%) screened positive for antepartum mental morbidities, of
      which depression was the most common. 3.8% of all women screened positive for
      depression, with 15.4% demonstrating depressive symptoms. Overall, 82 (39.4%) had
      the presence of one or more psychological symptoms, including fatigue,
      irritability, anxiety, and problems with sleep and concentration but scored less
      than the CIS-R cutoff score of 12. Factors associated with the presence of
      antepartum mental morbidities included poor relationships with their spouse,
      poor/satisfactory relationship with siblings or in-laws, as well as the desire to
      have a male child. Conclusion: In the study population, 12 (5.8%) screened
      positive for antepartum mental morbidities. Considering the effects on quality of
      life for these women as well as poor fetal outcomes associated with maternal
      mental morbidity, it is important to include screening and treatment of mental
      morbidity as a part of routine antenatal care.

PMID- 30093747
TI  - Challenges in Taking Sexual History: A Qualitative Study of Indian Postgraduate
      Psychiatry Trainees.
AB  - Context: In India, psychiatrist is an important point of helpseeking for sexual
      complaints. A detailed sexual history can go a long way in understanding sexual
      difficulties. In this background, there is inadequate information on the
      difficulties that psychiatry postgraduate trainees experience while taking a
      sexual history as part of a routine mental health evaluation. Aims: The aim was
      to study the difficulties experienced by postgraduate psychiatry trainees while
      taking sexual history as a part of routine mental health evaluation. Setting:
      This study was conducted in an Indian medical college general hospital psychiatry
      setting. Materials and Methods: This is a qualitative study using focus group
      discussions and in-depth interviews with postgraduate psychiatry trainees.
      Statistical Analysis: Content analysis was used to identify direct and latent
      themes. Results: Thematic saturation was achieved with 17 participants. Major
      themes of difficulties that emerged included trainee-related factors such as
      gender and sociocultural background of the trainee; patient-related factors such
      as age, gender, and sexual orientation; setting-related factors; and language
      related difficulties. Conclusions: Specific and regular training in taking a
      sexual history is essential in addressing the difficulties faced by postgraduate
      psychiatry trainees in India.

PMID- 30093746
TI  - The Pattern of Psychiatric Morbidity in an Outpatient Child Psychiatry Clinic: A
      Cross-sectional, Descriptive Study from a Tertiary Care Hospital in Kashmir,
      North India.
AB  - Background: Psychiatric disorders are ubiquitous and affect not only adults but
      also children and adolescents. The age factor plays an important role in the
      pattern of these psychiatric disorders. The objective of our study was to find
      the pattern of psychiatric morbidity in children and adolescents at the child and
      adolescent outpatient service of a tertiary care hospital. Materials and Methods:
      A semi-structured questionnaire was used to record the sociodemographic status.
      The state of mental health and psychiatric morbidity was assessed after a
      thorough clinical assessment. Intelligence quotient was assessed by a clinical
      psychologist as and when needed. All the diagnoses were made on the basis of
      Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision
      criteria. Results: A total of 529 patients were included. Most patients belonged
      to the age group of 6-16 years (70.5%). Boys (67.9%) outnumbered girls. Most of
      the patients were from rural background (56.7%) and from nuclear families (53%).
      Attention-deficit hyperactivity disorder (31%) and mental retardation (29%) were
      the most frequent diagnoses, followed by pervasive developmental disorders (10%).
      Comorbidity was present in about 18% of our patients. Conclusion: The child
      psychiatry is gaining acceptance, and children and adolescents with minor mental
      health issues are being identified and referred for specialized services.

PMID- 30093749
TI  - Alopecia Associated with Use of Methylphenidate: A Case Series.
AB  - In this case series, we report three cases of alopecia associated with use of
      methylphenidate for ADHD (Attention deficit hyperactivity disorder), that
      reversed with discontinuation of methylphenidate.

PMID- 30093748
TI  - An Epidemiological Study on Empathy and its Correlates: A Cross-sectional
      Assessment among Medical Students of a Government Medical College of India.
AB  - Background: Empathy is a desirable quality in every clinician. It is a crucial
      determinant of patient-physician communication and relation. There are very few
      existent Indian studies on empathy of medical students and its correlates. Aim:
      The aim of the study was to assess empathy level of medical students and its
      correlates. Methodology: It was a cross-sectional, hospital-based, analytical
      observational study conducted from July to November 2017. In total, 249
      undergraduate medical students of a medical college of Kolkata were interviewed
      with a structured schedule. The schedule comprised of the sociodemographic
      questionnaire, career satisfaction, future career choice, and Jefferson Scale of
      Empathy. Results: The mean empathy score was 98.5 +/- 12.5. Third-semester
      students had higher empathy scores (102.4 +/- 12.4) compared to fifth (97.2 +/-
      12.9) and seventh semester (95.0 +/- 10.9) students. The difference between the
      mean scores of different semesters was statistically significant. Female students
      were more empathic than male students. In the multivariable linear regression
      model, sex, semester, residence, career satisfaction, future career choice, and
      current place of living were significant predictors of empathy scores.
      Conclusion: Empathy level of medical students of our study was quite low compared
      to other studies conducted outside India. Empathy eroded with semester, which
      supports earlier pieces of evidence in this regard.

PMID- 30093750
TI  - A Rare Presentation of Psychotic Depression with Suicidality in a Case of
      Papillon-Lefevre Syndrome.
AB  - Papillon-Lefevre syndrome (PLS) is an autosomal recessive disorder that presents
      with palmoplantar hyperkeratosis and childhood-onset progressive loss of all
      dentition. Mental retardation is the only neurodevelopmental disorder reported
      with this condition till date. We report the first ever case in the literature of
      PLS presenting with psychotic depression and suicidal intention. A 40-year-old,
      never married, unemployed woman presented for psychiatric consultation and was
      given an International Classification of Diseases version 10 diagnosis of severe
      depression with psychotic symptoms. Physical examination warranted dermatological
      and dental evaluation before electroconvulsive therapy (ECT) could be
      administered. She was diagnosed with PLS and pseudoainhum by the skin and dental
      specialists. Karyotyping study was normal, and histopathology of the palmar
      tissue showed hyperkeratinization. She was treated with ECT, duloxetine and
      olanzapine, and she achieved full remission of her depression. She was prescribed
      oral retinoids and emollients for the skin disorder, and there was a good
      improvement. The dental prosthesis was fixed, and she was able to eat and feel
      better than before. Early diagnosis of this condition and rehabilitation would be
      important in improving wellbeing.

PMID- 30093751
TI  - Clozapine-induced Insulin-resistant Hyperglycemia in a Diabetic Patient.
AB  - Clozapine is superior to all other antipsychotics in treatment-resistant
      schizophrenia. However, metabolic side effects are common while treating patients
      with clozapine. Administering clozapine in a patient who already is diabetic
      involves careful weighing of risks and benefits. Here, we report our experience
      of starting clozapine in a known diabetic patient. Clozapine was started in a
      patient with treatment-resistant psychosis in view of suicidal risk. Her diabetes
      mellitus was under good control with oral medications. After initiation of
      clozapine, blood sugars increased several fold within few days. Blood glucose
      continued to increase even with high doses of insulin and insulin infusion.
      Finally, blood sugars came under control only after discontinuation of clozapine.
      Precautionary measures while initiating clozapine in a diabetic patient are
      suggested - close monitoring of blood sugar during the initial few days and
      intensive intervention if blood sugar levels increase. Discontinuation of
      clozapine should also be kept in mind as a last resort.

PMID- 30093752
TI  - Lithium-induced Symptomatic Hypercalcemia and Hyperparathyroidism in a Patient
      with Bipolar Affective Disorder: A Case Report and Review of Literature.
AB  - Lithium induced primary hyperparathyroidism is an uncommon endocrine side effect
      of long term lithium therapy. We studied the case of a 67-year-old female patient
      on long term lithium therapy for bipolar affective disorder, who developed
      resistant hypercalcaemia and parathyroid adenoma which required
      parathyroidectomy. Furthermore, the effect of chronic lithium therapy on
      parathyroid glands and serum calcium levels, its pathogenesis, and management
      were reviewed. Periodic monitoring of serum calcium levels in patients on long
      term lithium therapy should be practiced. Surgical removal of the affected
      parathyroid gland is an effective treatment modality in selected patients with
      resistant hypercalcaemia and parathyroid adenoma and/or hyperplasia. However,
      regular post-operative follow up is needed for early identification of recurrence
      in such patients.

PMID- 30093753
TI  - Empowering People with Disabilities.

PMID- 30093754
TI  - Clozapine-induced Weight Loss and Stuttering in a Patient with Schizophrenia.

PMID- 30093755
TI  - Psychological Interventions During Nipah Viral Outbreak in Kozhikode District,
      2018.

PMID- 30093757
TI  - A Comment on "Blue Whale Challenge: Perceptions of First Responders in Medical
      Profession".

PMID- 30093756
TI  - Off-label Psychotropics Use: Isn't it Now an Inevitable and a "Norm" in
      Psychiatry?

PMID- 30093758
TI  - Comments on "Efficacy of Transcranial Direct Current Stimulation in the
      Treatment: Resistant Patients Who Suffer from Severe Obsessive-compulsive
      Disorder".

PMID- 30093759
TI  - Prenatal Depression and Infant Health: The Importance of Inadequately Measured,
      Unmeasured, and Unknown Confounds.
AB  - A recent study found that maternal antenatal depressive symptoms were associated
      with adverse infant general health outcomes and that gestational age, birth
      weight, and breastfeeding did not mediate the observed relationship. The authors
      suggested that antenatal depression can have a harmful effect on infant health
      through disturbed fetal programming driven by maternal symptoms and behaviors
      that influence the maternal and hence the fetal internal environment. The authors
      implied that interventions to diagnose and treat maternal depression can have a
      protective effect against disturbances in infant health. However, because of the
      observational nature of the study, cause-effect relationships cannot be
      conclusively stated. This is especially so because there were many confounds that
      the authors did not consider. The present article provides examples and
      explanations of how inadequately measured, unmeasured, and unknown confounds can
      explain observed relationships between explanatory and outcome variables, thereby
      negating cause-effect interpretations of study findings. It is important to
      minimize confounding when conducting observational studies, and this can only be
      done by comprehensively listing and efficiently measuring potential confounders
      in advance.

PMID- 30093760
TI  - Erratum: Diagnostic Apraxia and Ictal Alien Hand.
AB  - [This corrects the article on p. 284 in vol. 40, PMID: 29875540.].

PMID- 30093761
TI  - Tuberculosis diagnosis in resource limited settings.

PMID- 30093762
TI  - Brain stem death certification protocol.
AB  - Transplantation of Human Organs is guided by laid down specific Laws in India.
      The organs which are targeted to be transplanted are liver, kidney and cornea.
      The waiting list is enormous but the donor pool is meagre. This document has been
      made with a view that the donor pool can be enlarged by identifying patients who
      are 'Brain Dead' while still not having 'Cardiac Death'. The steps include the
      prerequisite conditions which must be satisfied by patients who have suspicion of
      being brain dead, detailed examination of the patient, confirmation of the Brain
      Death and Counselling of the relatives for organ donation.

PMID- 30093763
TI  - Knowledge of breastfeeding practices in doctors and nurses: A questionnaire-based
      survey.
AB  - Background: As the primary physicians and nurses in hospitals are the first
      contact with the mothers, we carried out a questionnaire-based survey to assess
      the knowledge of the MBBS nonspecialist doctors and general duty nurses regarding
      breastfeeding of normal newborns. Methods: Thirty-four MBBS, nonspecialist
      doctors and ninety-seven general duty nurses were enrolled in the study between
      August 2016 and September 2016 in a tertiary care teaching hospital, and a
      questionnaire comprising of 10 questions on breastfeeding was provided to each.
      Results: All doctors (100%) and nurses (100%) agreed that breastfeeding must be
      started within 1 h of birth and all nurses (100%) agreed that breastfeeding alone
      is sufficient for a newborn baby during the first 2-3 days of life. However,
      58.8% of the doctors and 25.7% of the nurses believed that after 6 months of
      life, the mother must give her infant cow's milk or formula for better growth.
      Only 52.9% of doctors and 40.2% of nurses agreed that breastfeeding should be
      advised to be continued for 2 years and beyond. Among doctors only 67.6% believed
      that breastfeeding for a normal newborn should be on demand only and not by
      clock. Conclusion: There is scope of improvement regarding knowledge of
      breastfeeding in both doctors and nurses. All healthcare providers must provide
      correct information to mothers to help them in successful breastfeeding.

PMID- 30093764
TI  - Evaluation of manual Mycobacterium growth indicator tube for isolation and
      susceptibility testing of Mycobacterium tuberculosis for implementation in low
      and medium volume laboratories.
AB  - Background: Manual Mycobacterium growth indicator tube (MGIT) was evaluated for
      isolation and drug susceptibility testing (DST) of Mycobacterium tuberculosis
      (MTB) for its implementation in laboratories with low and medium volume. Methods:
      1018 consecutive clinical specimens were processed using manual MGIT and
      conventional Lowenstein-Jensen (LJ) culture. Results obtained for culture
      positivity were analyzed taking combined reference of positivity by either solid
      or liquid culture. All positive cultures were identified and DST to first line
      drugs was performed by manual MGIT and 1% proportional method on LJ media.
      Performance of manual MGIT for DST was compared to conventional DST on LJ media.
      Result: Of the total 220 culture positive samples 93.9% were isolated in MGIT
      while 75.7% in LJ taking combined reference of positivity by either solid or
      liquid culture. Turn around time for isolation of MTB was significantly less for
      MGIT as compared to LJ. There was good agreement between manual MGIT and 1%
      proportional method on LJ media for DST to first line drugs. Turnaround time from
      inoculation to DST results for smear positive and smear negative cases using
      manual MGIT was 20.2 and 30.1 days respectively. The total cost for isolation,
      identification and DST in manual MGIT for smear positive and smear negative cases
      was INR 2350 and INR 2700 respectively. Conclusion: It is feasible to implement
      manual MGIT in low to medium volume laboratory that already has experience with
      culture provided adequate biosafety measures and appropriate training of
      laboratory staff are taken care of.

PMID- 30093765
TI  - Ultrasound evaluation of cervical lymphadenopathy: Can it reduce the need of
      histopathology/cytopathology?
AB  - Background: The differentiation between the causes of cervical lymphadenopathy is
      of paramount importance as these have different modalities of treatment with
      varying prognosis. The aim of this study was to evaluate the efficacy of B Mode
      and colour Doppler ultrasound (CDUS) to differentiate between benign and
      metastatic lymph nodes. Methods: 100 patients of clinically palpable lymph nodes
      were evaluated with B Mode and CDUS. B Mode assessment included short-long (S:L)
      axis ratio, hilum, nodal border, echogenicity, intranodal necrosis and ancillary
      features. CDUS assessment included distribution of vascularity, resistive index
      (RI) and pulsatility index (PI). Statistical analysis was carried out with
      histopathological or cytological diagnosis as gold standard. Results: B-Mode US
      correctly diagnosed 22/25 (88%) of the reactive lymph nodes giving it a
      sensitivity of 88% and specificity of 97.3%. Colour Doppler US diagnosed 23/25
      (92%) reactive lymph nodes with a sensitivity of 92% and specificity of 97.3%. B
      Mode underdiagnosed one case each of granulomatous disease and metastasis as
      reactive node while CDUS missed out two cases of granulomatous disease as
      reactive lymph node. Conclusion: Individual parameters of B Mode when used alone
      were not found to be very effective in differentiating benign and malignant lymph
      nodes. However features of B-Mode combined together as well as color Doppler
      ultrasound, help in the detection of reactive lymph nodes and can be used as a
      diagnostic tool with good accuracy. However, they cannot be used as a diagnostic
      method for metastatic or tubercular nodes and cytopathology/histopathology
      remains the gold standard in such situations.

PMID- 30093766
TI  - Iron deficiency anemia in children with cyanotic congenital heart disease and
      effect on cyanotic spells.
AB  - Background: Iron deficiency anemia (IDA) in cyanotic congenital heart disease
      (CCHD) and its association with cyanotic spells has been documented in
      literature. However, Indian data especially in the pediatric age group is scarce.
      This study was conducted to find out the prevalence of IDA in this population.
      Methods: An observational study was conducted in a tertiary care hospital.
      Children with CCHD in the age group of birth-12 years were included in the study.
      Hematological parameters of these patients were determined and compared. An
      assessment of the incidence of cyanotic spells in the iron-deficient and iron non
      deficient children was also done. Data analysis was done using Fischer's exact
      test. Results: The prevalence of IDA was 47.06% in the study population. The
      study also showed that hemoglobin and hematocrit levels were paradoxically higher
      in the iron-deficient group as compared to the non-deficient, though the iron
      studies revealed the iron deficiency. The incidence of cyanotic spells was higher
      in the iron-deficient group. The mean corpuscular volume (MCV), red cell
      distribution width (RDW), serum ferritin, serum iron, total iron binding capacity
      (TIBC), and transferrin saturation (TS) values were the parameters, which were
      found to be statistically significant to differentiate the study groups.
      Conclusion: The prevalence of IDA in children with CCHD was found to be high.
      Iron-deficient group had an increased frequency of cyanotic spells as compared to
      the non-deficient group, which was statistically significant.

PMID- 30093768
TI  - Prevalence and the risk factors of gastro-esophageal reflux disease in medical
      students.
AB  - Background: Gastroesophageal reflux disease (GERD) is a commonly prevalent
      gastrointestinal disorder in adults. Very few studies on magnitude of GERD in
      student community have been done and there is none so far from India. Rigorous
      MBBS curriculum makes medical students prone for reflux symptoms. Hence, this
      study was conducted to determine the prevalence of GERD in medical students and
      the potential risk factors associated with it. Methods: This was a cross
      sectional observational study conducted on medical students in a premier medical
      college of India. All participants were interviewed for GERD symptoms using the
      validated questionnaire on frequency scale for the symptoms of GERD. Additional
      11 questions include enquiries on medical history and lifestyle factors. Results:
      Of the 600 students, 150 (25%) had GERD symptoms. Of these, 88 (58.6%) had mild,
      58 (38.6%) moderate, and 4 (2.7%) severe reflux symptoms. Fifty eight (38.6%) of
      students with GERD had associated dyspepsia. On univariate analysis higher BMI,
      final years of MBBS course, use of NSAID or alcohol, inadequate sleep, sleeping
      within one hour of taking dinner, missing breakfast regularly and quick eating
      were significantly associated with GERD (p < 0.05). Conclusions: Prevalence of
      symptoms of GERD in medical students is 25%, majority had mild symptoms.
      Associated dyspeptic symptoms were present in 38.6%. Factors predisposing to GERD
      in them are higher BMI, final years of MBBS course, use of NSAID, inadequate
      sleep, sleeping within one hour of taking dinner, missing breakfast on regular
      basis and quick eating.

PMID- 30093767
TI  - Determinants of adverse treatment outcomes among patients treated under Revised
      National Tuberculosis Control Program in Wardha, India: Case-control study.
AB  - Background: Tuberculosis (TB) leads to a considerable loss of lung functions and
      Quality Adjusted Life Years. Several factors are associated with adverse
      treatment outcomes from TB which further increases this loss. We undertook the
      study to study the determinants of adverse treatment outcomes among tuberculosis
      patients treated under the Revised National Tuberculosis Control Program in a
      tuberculosis unit in India. Methods: 88 cases and 187 controls from among
      patients registered in Wardha Tuberculosis Unit in the year 2014 were interviewed
      to study the determinants of adverse treatment outcomes of tuberculosis. All
      patients with adverse treatment outcomes were taken as cases. Controls were
      chosen from relapse free successfully treated patients using simple random
      sampling. Results: On multivariate analysis indoor air pollution, pulmonary TB,
      discrimination due to TB and poor satisfaction with services significantly
      increased the odds of adverse treatment outcomes whereas the senior treatment
      supervisor visiting the patients during treatment was protective. Conclusion:
      Appropriate new interventions and strengthening of the existing mechanisms to
      reduce treatment interruptions along with proper implementation of the program
      will help in reducing the adverse treatment outcomes and improving program
      performance.

PMID- 30093769
TI  - Comparison of balloon dacryocystorhinostomy with conventional endonasal
      endoscopic dacryocystorhinostomy for relief of acquired distal nasolacrimal
      drainage obstruction and its impact on quality of life: A prospective,
      randomized, controlled study.
AB  - Background: We compared balloon dacryocystorhinostomy with conventional
      endoscopic dacryocystorhinostomy for the management of acquired distal
      nasolacrimal obstruction and the quality of life post procedure. Methods: 98
      patients, aged 10-73 years, were recruited and randomized into 2 groups of 49
      each who underwent conventional endoscopic dacryocystorhinostomy (group 1) and 9
      mm balloon assisted endoscopic dacryocystorhinostomy (group 2). Follow-up
      sessions were conducted at 3, 6 and 12 months post-op. Results: Group 2 showed
      significantly shorter mean operative time (25.10 min versus 29.82; p < 0.001),
      lesser pain in the post-op evening (mean 2.12 versus 2.9 on NRS-11 pain scale; p
      < 0.001) as well as on first post-op day (mean 1.08 versus 1.73; p < 0.001).
      Success was achieved in 89.79% in group 1 and 93.87% in group 2 at 3 months (p =
      0.46) which declined due to recurrences to 85.71% and 87.75% respectively at 12
      months (p = 0.76). Complications occurred in 14 cases in group 1 and in 10 cases
      in group 2 (p = 0.34). All were minor. Mean GBI scores (for quality of life
      assessment) at 12 months follow-up were 27.20 and 28.38 respectively (p = 0.08).
      Conclusion: The efficacy, safety and quality of life of balloon
      dacryocystorhinostomy and conventional endoscopic dacryocystorhinostomy were
      comparable. In addition, balloon dacryocystorhinostomy had significantly shorter
      operative time and lesser post-op pain.

PMID- 30093770
TI  - Evaluation of cases of membranoproliferative glomerulonephritis according to
      newer classification: A retrospective record-based study.
AB  - Background: Membranoproliferative glomerulonephritis (MPGN) has traditionally
      been classified on electron microscopy (EM) into different types based on the
      location of the immune complexes. Sethi et al. subsequently suggested a more
      relevant etiology-based and clinically useful classification based on
      immunofluorescence. Methods: In this retrospective study, 18 diagnosed cases of
      MPGN over a one-year period for which direct immunofluorescence (DIF) study
      results were available, were selected. Cases without archived records of
      immunofluorescence photographs/reports were excluded. Histological diagnosis of
      MPGN was confirmed and DIF results were analyzed with reference to antibodies to
      IgG, IgA, IgM, C3, C1q, kappa, and lambda light chains. Results: Evaluation of
      cases revealed 8 males and 10 females with age range from 11 to 66 years. Fifteen
      cases presented with nephrotic syndrome. On evaluation, 88.89% cases (16/18) were
      immune complex mediated while two (11.11%) were of complement mediated type of
      MPGN. Among immune complex-mediated cases, a single case of monoclonal gammopathy
      associated or light chain mediated MPGN was present. Conclusion: The
      classification described by Sethi et al. is easy to use since it relies on DIF
      instead of EM which is not readily available. Most of the cases were immune
      complex mediated whereas incidence of complement mediated MPGN, that is, C3
      glomerulopathy was low (11.11%). Application of the new classification allows
      more relevant categorization of cases based on etiology and without the
      requirement of EM.

PMID- 30093772
TI  - Ocular surface squamous neoplasia.

PMID- 30093771
TI  - Cutaneous myiasis: Think beyond furunculosis.
AB  - Background: Cutaneous myiasis is the infestation of the skin by larvae (maggots)
      of the order Diptera (two winged). Being an imported and sporadic illness,
      furuncular myiasis often poses a diagnostic challenge to the treating physician.
      This traditionally endemic entity is being more frequently reported worldwide as
      'vacation' disease in travellers returning from these regions. However, there is
      a paucity of large scale study, especially on individuals occupationally
      stationed for longer periods of time in these endemic geographic locations.
      Methods: Sixteen Indian male patients with cutaneous furuncular myiasis
      presenting to dermatology outpatient department at a tertiary care field hospital
      deployed in a United Nations peacekeeping mission in Central Africa were studied
      for clinical presentation, sites involved, larvae/maggot extracted, period of
      resolution and complications if any. Results: Average age of patients was 29
      years. The average duration of infestation was 4 days. All lesions were found to
      be confined to sites over body normally covered with clothing, commonest being
      anterior abdomen in 9 (56.25%) patients followed by chest in 6 (37.5%) patients.
      The lesion count was also highest on anterior abdomen with 39 lesions. The
      average time to resolution following extraction of larvae (Cordylobia
      anthropophaga) was 6 days. Conclusion: The purpose of this study was to
      familiarize oneself with an endemic infestation which often masquerades itself as
      pyoderma to the naive physician, more so in an imported case or more importantly,
      an 'exported' health care professional.

PMID- 30093773
TI  - A case of spermatocytic seminoma in young individual.

PMID- 30093774
TI  - Idiopathic CD4 lymphocytopenia presenting with progressive disseminated
      histoplasmosis.

PMID- 30093775
TI  - Simulum fly bites.

PMID- 30093776
TI  - Artery first approach for resecting ganglioneuroma encasing superior mesenteric
      artery.

PMID- 30093777
TI  - Non-traumatic rupture of eventration of diaphragm in a child.

PMID- 30093778
TI  - Pericardial tamponade: Rare complication of subclavian vein cannulation.

PMID- 30093779
TI  - Episiotomy scar endometriosis.

PMID- 30093780
TI  - A case of 'blue skin' and 'dark urine'.
AB  - A 60-year-old female presented with a 20-year history of progressive dark bluish
      discoloration of skin and passage of dark colored urine, painful arthritis and a
      recent history of invasive ductal carcinoma of right breast. Skin biopsy revealed
      hyaline material which was Periodic-Acid-Schiff stain positive and Congo-red
      stain negative, urine analysis revealed dark urine with presence reducing
      substance and radio-imaging showed intervertebral ossification and joint
      ankyloses. The patient was managed symptomatically with physiotherapy and
      acetaminophen on as required basis. This image is reported as a classic case of
      Alkaptonuria with clinical, histopathological and radio-imaging findings and the
      presence of invasive ductal breast carcinoma in the same patient.

PMID- 30093781
TI  - MR Geyser Sign in chronic rotator cuff tears.
AB  - Acromio-clavicular (AC) joint cysts are rare presentation of chronic shoulder
      pathology. These cysts may be observed secondary to either degenerative changes
      in the AC joint with an intact rotator cuff (type 1 cyst) or following a chronic
      rotator cuff tear (type 2 cyst). The latter phenomenon is known as Geyser Sign
      and is described by ultrasound, conventional arthrogram and magnetic resonance
      imaging (MRI). We present a case of chronic rotator cuff tear presenting with a
      large type 2 cyst and Geyser Sign on MRI.

PMID- 30093782
TI  - Dental implant rehabilitation: From fail to pass..!!

PMID- 30093783
TI  - Qualitative ultrasonography for bone health: Are we there yet?

PMID- 30093784
TI  - Role of pathology peer review in interpretation of the comet assay.
AB  - When a comet assay, an increasingly popular in vivo genotoxicity test, shows a
      positive test result, interpretation of that response requires ruling out any
      confounding tissue site toxicity. Since the comet assay typically uses only two
      or three daily doses of test agent, precursor tissue changes indicative of
      toxicity may be easily overlooked. Using case examples for two flavoring agents,
      perillaldehyde and 4,5-epoxydec-2(trans)-enal, we highlight the role of pathology
      peer review in verifying precursor tissue changes indicative of tissue site
      toxicity, thereby increasing confidence in final interpretation of comet assay
      results. Given global deliberation regarding safety assessment of compounds
      entering the marketplace, we recommend consideration of pathology peer review for
      equivocal and positive comet assays so that interpretations are universally
      consistent.

PMID- 30093785
TI  - gammaH2AX is immunohistochemically detectable until 7 days after exposure of N
      bis (2-hydroxypropyl) nitrosamine (DHPN) in rat lung carcinogenesis.
AB  - It is known that gammaH2AX, which is formed when there is a double-strand break
      in DNA, can act as a sensitive marker of genomic instability. In this experiment,
      the time-course manner of the expression of gammaH2AX in the lung was examined in
      the early phase after treatment with a lung carcinogen, N-bis (2-hydroxypropyl)
      nitrosamine (DHPN). The expression of gammaH2AX is expected to be one of the
      useful markers for lung carcinogenesis in early stages. Rats were separated into
      10 groups of 5 rats. The DHPN groups were administered 0.1% DHPN in drinking tap
      water for two weeks, while the control group received drinking tap water. At 0,
      1, 3, 7, and 14 days after finishing DHPN treatment, one group each from the DHPN
      and control groups was sacrificed. The removed lung tissues were examined for
      immunostaining of gammaH2AX and PCNA, and positive cells were counted. The
      gammaH2AX levels of the DHPN-treated groups were found to be increased
      significantly at 0, 1, 3, and 7 days (4.4 +/- 1.4, 5.1 +/- 2.7, 3.3 +/- 1.0, and
      4.1 +/- 1.3%, respectively), and they dropped significantly on day 14 (1.1 +/-
      0.4%). The experiment showed that the gammaH2AX-positive score could be
      effectively measured for up to 7 days after exposure, as a significance
      difference was observed between the treated group and the control group. It can
      be deduced that gammaH2AX is an effective marker for DHPN-induced double-strand
      breaks in pulmonary epithelial cells.

PMID- 30093786
TI  - Role of oxidative stress in the chemical structure-related genotoxicity of
      nitrofurantoin in Nrf2-deficient gpt delta mice.
AB  - Despite its antimicrobial activity, nitrofurantoin (NFT) is a renal carcinogen in
      rats. Oxidative stress induced by reduction of the nitro group of NFT may
      contribute to its genotoxicity. This is supported by our recent results
      indicating that the structure of the nitrofuran plays a key role in NFT-induced
      genotoxicity, and oxidative DNA damage is involved in renal carcinogenesis.
      Nuclear factor erythroid 2-related factor 2 (NRF2) regulates cellular responses
      to oxidative stress. To clarify the role of oxidative stress in the chemical
      structure-related genotoxic mechanism of NFT, we performed reporter gene mutation
      assays for NFT and 5-nitro-2-furaldehyde (NFA) using Nrf2-proficient and Nrf2
      deficient gpt delta mice. NFT administration for 13 weeks resulted in a
      significant increase in 8-hydroxydeoxyguanosine (8-OHdG; a marker of oxidative
      stress) and gpt mutant frequency only in the kidneys of Nrf2-/- mice. The
      mutation spectrum, characterized by increased substitutions at guanine bases,
      suggested that oxidative stress is involved in NFT-induced genotoxicity. However,
      NFA did not increase the mutation frequency in the kidneys, despite the increased
      8-OHdG in NFA-treated Nrf2-/- mice. Thus, it is unlikely that oxidative stress is
      involved in the genotoxic mechanism of NFA. These results imply that nitro
      reduction plays a key role in the genotoxicity of NFT, but the lack of a role of
      oxidative stress in the genotoxicity of NFA indicates a potential role of side
      chain interactions in oxidative stress caused by nitro reduction. These findings
      provide a basis for the development of safe nitrofurans.

PMID- 30093787
TI  - Mechanisms of oxidative stress-induced in vivo mutagenicity by potassium bromate
      and nitrofurantoin.
AB  - Oxidative stress is well known as a key factor of chemical carcinogenesis.
      However, the actual role of oxidative stress in carcinogenesis, such as oxidative
      stress-related in vivo mutagenicity, remains unclear. It has been reported that 8
      hydroxydeoxyguanosine (8-OHdG), an oxidized DNA lesion, might contribute to
      chemical carcinogenesis. Potassium bromate (KBrO3) and nitrofurantoin (NFT) are
      known as renal carcinogens in rats. Our previous studies showed an increase in
      mutant frequencies accompanied by an increased level of 8-OHdG in the kidneys of
      rodents following KBrO3 or NFT exposure. Furthermore, KBrO3 and NFT induced
      different types of gene mutations. Thus, in the present study, we performed
      reporter gene mutation assays and 8-OHdG measurements following KBrO3 or NFT
      exposure using Nrf2-proficient and Nrf2-deficient mice to clarify the
      relationship between KBrO3- or NFT-induced oxidative stress and subsequent
      genotoxicity. Administration of 1,500 ppm of KBrO3 in drinking water resulted in
      an increase in deletion mutations accompanied by an increase in 8-OHdG level, and
      administration of 2,500 ppm of NFT in diet induced an increase in guanine base
      substitution mutations without elevation of the 8-OHdG level in Nrf2-deficient
      mice. These results demonstrated that the formation of 8-OHdG, which resulted
      from the oxidizing potential of KBrO3, was directly involved in the increase in
      deletion mutations, although factors related to oxidative stress other than 8
      OHdG might be crucial for NFT-induced guanine base substitution mutations. The
      present study provides new insight into oxidative stress-related in vivo
      mutagenicity.

PMID- 30093788
TI  - A case of rapid recurrence of apocrine ductal carcinoma originating from the oral
      scent gland of a Richardson's ground squirrel (Urocitellus richardsonii).
AB  - A 3-year-old female Richardson's ground squirrel developed a subcutaneous mass at
      the left oral angle. Seven days after removal of the mass, the mass recurred and
      metastasized to the cervical lymph node. Histologically, the primary mass was
      subdivided by fibrous trabeculae into various-sized neoplastic cell lobules
      showing a solid growth pattern with frequent mitoses and sometimes forming
      intracytoplasmic lumina. Large to medium-sized lobules formed a central cyst
      plugged by comedo necrosis. Neoplastic cells showed infiltrative subcutaneous
      growth. In the recurrent tumor, tubular structures lacking apparent apocrine
      secretion appeared within the solid growth portion. Neutrophil infiltration was
      evident within the tubules and intracytoplasmic lumina. Neoplastic cells were
      diffusely immunopositive for AE1/AE3 pan-cytokeratin (CK) in all lobules and
      focally positive for CAM5.2 CK in the lobules forming a central cyst and/or
      tubular structures, but they entirely lacked positivity for the periodic acid
      Schiff reaction. Ki-67-positive proliferating neoplastic cells were higher in
      numbers with the recurrent tumor than with the primary tumor. In addition,
      phosphorylated c-MYC immunoreactivity was observed in neoplastic cell nuclei,
      distinctly at the portion of invasive growth. Thus, the present case was
      diagnosed as apocrine ductal carcinoma originating from the oral scent gland,
      which typically shows highly aggressive biological behavior.

PMID- 30093789
TI  - Spontaneous pulmonary co-metastasis of hepatoblastoma arising within a
      hepatocellular carcinoma in an aged C57BL/6J mouse.
AB  - Murine hepatoblastoma (HB) is a rare spontaneous tumor with controversial
      histogenesis. It mainly occurs in aged males, frequently in close association
      with preexisting hepatocellular neoplasms. The present work describes a
      spontaneous HB arising within a hepatocellular carcinoma (HCC) in a 22-month-old
      male C57BL/6J mouse. The mouse also developed pulmonary co-metastases with either
      tumor components physically associated within the same metastatic foci.
      Microscopically, the HB consisted of a densely cellular neoplastic growth
      composed of palisades and perivascular pseudorosettes of poorly differentiated
      primitive cells, with a scant amount of cytoplasm, elongated hyperchromatic
      nuclei, and a high mitotic rate, whereas the hepatocellular carcinoma was
      composed of solid areas of neoplastic hepatocytes. Both in primary tumors and
      their metastases, beta-catenin immunohistochemistry revealed a strong
      nucleocytoplasmic signal in HB cells, while neoplastic hepatocytes displayed a
      delicate membranous staining pattern. These findings suggest that the Wnt/beta
      catenin oncogenic pathway is upregulated in murine HB but not in the co-existing
      HCC, thus providing some insights into their divergent pathogenesis. Coexisting
      murine HB and HCC have been demonstrated to be completely distinct entities
      including origin, mutational landscape, and molecular profile. In this context,
      they might be regarded as collision tumors because of their intimate association,
      unique histologic features, and distinct immunohistochemical patterns.
      Nevertheless, the nature of their coevolution and progression to a co-metastatic
      phenotype reflects a close interdependence and support the overall idea that HB's
      origin and progression might be promoted by not otherwise specified paracrine
      stimuli provided by the concurrent hepatocellular tumor (the so called
      "interaction theory").

PMID- 30093790
TI  - Improved fixation of the whole bodies of fish by a double-fixation method with
      formalin solution and Bouin's fluid or Davidson's fluid.
AB  - To prevent fixation defects or artifacts in the whole bodies of fish caused by
      conventional fixatives, such as formalin solution, Bouin's fluid (BF), and
      Davidson's fluid (DF), the optimal fixatives and fixing method were examined. An
      improved method of fixing the whole bodies of fish was examined that makes use of
      a combination of 20% formalin and BF or DF. The fixatives were examined with four
      representative tissues, i.e., the gill, liver, intestinal tract, and kidney, to
      evaluate end points including the appearance of degraded tissues and artifacts
      caused by each fixative, overall morphological clarity of nuclei, staining
      intensity, and integrity of the other tissues. The best results were obtained
      when the fresh whole bodies were initially fixed in 20% formalin (primary
      fixation) at 4 degrees C for 1 h and subsequently fixed in BF for 5 h at 4
      degrees C (secondary fixation). Therefore, the current findings led the authors
      to conclude that the combination of primary fixation with 20% formalin at 4
      degrees C for 1 h and secondary fixation with BF at 4 degrees C for 5 h was
      suitable for fixation of the whole bodies of fish.

PMID- 30093791
TI  - Immunohistochemical analyses of the kinetics and distribution of macrophages in
      the developing rat kidney.
AB  - Macrophages are required during kidney development and appear in the initiation
      and propagation of renal injury. To establish baseline data, we analyzed the
      kinetics of the macrophage with different immunophenotypes in the developing rat
      kidney (fetus at 18 and 20 days, neonate at 1-21 days, and adult at 7-weeks old).
      Macrophages reacting to CD68, CD163, and MHC class II were identified in the
      cortex and medulla of the developing rat kidney. CD68+ macrophages appeared in
      the fetal kidney as early as fetal day 18, and the number increased gradually in
      the neonatal kidney, whereas MHC class II+ and CD163+ macrophages first appeared
      on neonatal days 4 and 8, respectively. Apoptotic bodies were seen in the fetal
      kidney and early stages of the neonatal kidney (days 1-4), and simultaneously
      CD68+ macrophages appeared, indicating that CD68+ macrophages may have roles in
      phagocytosis of apoptotic bodies and contribute to renal tissue maturation.
      Colony stimulating factor 1 and insulin growth factor 1 mRNAs were increased in
      the late stage of renal development (neonatal day 12 or later), and
      simultaneously CD163+ and MHC class II+ cells appeared, suggesting that these
      cells may be a source of these growth factors and participate in renal tissue
      modeling. Generally, the CD163+ and MHC class II+ cell number was much smaller
      than that of CD68+ cells in the developing neonatal kidney. Therefore, the
      obtained findings provide valuable information on the participation of
      macrophages in the developing rat kidney. This information may be useful for
      evaluation of renal toxicity when macrophages are involved in the development of
      renal injury.

PMID- 30093792
TI  - PAXgene-fixed paraffin-embedded sample is applicable to laser capture
      microdissection with well-balanced RNA quality and tissue morphology.
AB  - Assessing how gene expression analysis by RNA sequencing (RNA-Seq) correlates to
      a unique morphology is increasingly necessary, and laser capture microdissection
      (LCM) is a critical research tool for discovering the genes responsible in a
      region of interest (ROI). Because RNA-Seq requires high-quality RNA, a sample
      preparation procedure that can preserve morphology and give the required quality
      of RNA is essential. A PAXgene(r)-fixed paraffin-embedded (XFPE) block can
      satisfy the need for high-quality RNA, but there are few reports on adapting the
      method for LCM, such as how small an ROI is analyzable by RNA-Seq. In this study,
      we confirmed the morphology and preservation of RNA in XFPE and then assessed the
      relationship between the size of pieces cut by LCM and their RNA quality. In
      XFPE, the morphology was similar to that in alcohol-based fixed samples, the
      quality of the RNA extracted from a whole sample was excellent, that is
      equivalent to that of a fresh frozen sample, and the quality was maintained over
      one year later. Three sizes of pieces-large (25,000 um2), medium (5,000 um2), and
      small (1,000 um2)-were cut by LCM so that the total areas of the sections cut per
      size were the same. RNA quality was found to be best preserved when tissue was
      cut into pieces of over 5,000 um2. In summary, XFPE exhibits good morphology and
      excellent preservation of RNA quality. Furthermore, it can be a good tool when
      used with LCM and RNA-Seq, giving well-balanced RNA quality and tissue morphology
      in the ROI.

PMID- 30093793
TI  - Imaging mass spectrometry for toxicity assessment: a useful technique to confirm
      drug distribution in histologically confirmed lesions.
AB  - To evaluate the usefulness of imaging mass spectrometry (IMS) technology for
      assessing drug toxicity, we analyzed animal tissues in an amiodarone (AMD)
      induced phospholipidosis model by IMS and confirmed the relationship between the
      distribution of AMD, its metabolites, and representative phospholipids
      (phosphatidylcholine, PC) and histological changes. AMD was administered to rats
      for 7 days at 150 mg/kg/day. The lung, spleen, and mesenteric lymph node were
      histologically examined and analyzed using IMS. The detection intensities of AMD,
      its metabolites, and typical PCs were higher in regions infiltrated by foamy
      macrophages compared with normal areas. This tendency was common in all three
      organs analyzed in this study. For the spleen, signals for AMD, its metabolites,
      and typical PCs were significantly more intense in the marginal zone, where foamy
      macrophages and vacuolated lymphocytes are abundant, than in the other areas.
      These results indicate that AMD, its metabolites, and PCs accumulate together in
      foamy or vacuolated cells, which is consistent with the mechanism of AMD-induced
      phospholipidosis. They also indicate that IMS is a useful technique for
      evaluating the distribution of drugs and biological components in the elucidation
      of toxicity mechanisms.

PMID- 30093794
TI  - Seeing Beyond the Margins: Challenges to Informed Inclusion of Vulnerable
      Populations in Research.

PMID- 30093796
TI  - Sequential Experimental Design for Optimal Structural Intervention in Gene
      Regulatory Networks Based on the Mean Objective Cost of Uncertainty.
AB  - Scientists are attempting to use models of ever-increasing complexity, especially
      in medicine, where gene-based diseases such as cancer require better modeling of
      cell regulation. Complex models suffer from uncertainty and experiments are
      needed to reduce this uncertainty. Because experiments can be costly and time
      consuming, it is desirable to determine experiments providing the most useful
      information. If a sequence of experiments is to be performed, experimental design
      is needed to determine the order. A classical approach is to maximally reduce the
      overall uncertainty in the model, meaning maximal entropy reduction. A recently
      proposed method takes into account both model uncertainty and the translational
      objective, for instance, optimal structural intervention in gene regulatory
      networks, where the aim is to alter the regulatory logic to maximally reduce the
      long-run likelihood of being in a cancerous state. The mean objective cost of
      uncertainty (MOCU) quantifies uncertainty based on the degree to which model
      uncertainty affects the objective. Experimental design involves choosing the
      experiment that yields the greatest reduction in MOCU. This article introduces
      finite-horizon dynamic programming for MOCU-based sequential experimental design
      and compares it with the greedy approach, which selects one experiment at a time
      without consideration of the full horizon of experiments. A salient aspect of the
      article is that it demonstrates the advantage of MOCU-based design over the
      widely used entropy-based design for both greedy and dynamic programming
      strategies and investigates the effect of model conditions on the comparative
      performances.

PMID- 30093795
TI  - Variants in the ABCA4 gene in a Brazilian population with Stargardt disease.
AB  - Purpose: The aim of this study was to analyze and report pathogenic variants in
      the ABCA4 gene in Brazilian patients with a clinical diagnosis of Stargardt
      disease. Methods: This retrospective study evaluated variants in the ABCA4 gene
      in Brazilian patients with Stargardt disease. The patients' visual acuity and age
      of symptom onset were obtained from previous medical records. The patients were
      classified according to the autofluorescence patterns. Results: Fifty patients
      aged between 10 and 65 years from 44 families were included in the study. Among
      these cases, the mean age of symptom onset was 14 years (range, 5-40 years).
      ABCA4 gene sequencing was conclusive in 40 patients (80%), negative in two
      patients (4%), and inconclusive in eight patients (16%). Four families carried
      homozygous pathogenic variants. Segregation analysis results were available for
      23 families. One novel variant was found: p.Ala2084Pro. The most frequent
      pathogenic variant in this group was p.Arg602Trp (12/100 alleles). Based on the
      phenotypic characteristics assessed with fundus autofluorescence imaging, 12
      patients were classified as having type I phenotype, 16 as having type II, and 18
      patients as having type III. The cases classified as type III phenotype included
      patients who were homozygous for the p.Asn96Asp and p.Arg2030* variants. One
      patient with a type I phenotype carried the homozygous intronic variant
      c.3862+1G>A. Conclusions: Next-generation sequencing was effective for the
      molecular diagnosis of genetic diseases and specifically allowed a conclusive
      diagnosis in 80% (40/50) of the patients. As the ABCA4 gene does not show a
      preferential region for pathogenic variants, the diagnosis of Stargardt disease
      depends on broader analysis of the gene. The most common pathogenic variants in
      the ABCA4 gene described in the literature were also found in these Brazilian
      patients. Although some genotype-phenotype correlations were found, more studies
      regarding the progression of Stargardt disease will help increase our
      understanding of the pathogenicity of these gene variants.

PMID- 30093798
TI  - Students Who Limit Their Drinking, as Recommended by National Guidelines, Are
      Stigmatized, Ostracized, or the Subject of Peer Pressure: Limiting Consumption Is
      All But Prohibited in a Culture of Intoxication.
AB  - There is an unquestionable need to address drinking patterns in subcultures where
      excessive drinking is normative. Regulatory bodies advocate moderating alcohol
      consumption but it is unclear whether individuals have agency to do so,
      particularly when excessive consumption is the norm. This study aimed to address
      this gap by examining student's perceptions of limiting consumption, as
      recommended by government guidelines, in one university in New Zealand. Using a
      qualitative social science approach, university students surveyed and interviewed
      their heavy-drinking peers (n = 201) to investigate perceptions of 3 drinking
      behaviors (Heavy, Moderation, and Abstinence). Thematic analysis revealed that
      students who drink heavily are labeled positively and viewed as sociable (Dr
      Froth, Liver of Steel, Trooper, Champion, Hero, Good Alcoholic, popular, a
      friend). Students who limit drinking, on the other hand, were viewed similar to
      those who abstain, labeled using explicit, emotive, and derogative terminology
      (eg, Fag, Vagina, Grandma, Weirdo, Coward, Killjoy) and excluded, ostracized, or
      the subject of peer pressure. They were also expected to provide a justification
      for moderating their drinking (eg, being an athlete, broke). Although individuals
      who moderated their consumption were perceived to have strong willpower and
      maturity (eg, self-aware, brave, sophisticated), these positive attributes were
      mentioned less frequently and involved less emotive language than were labels
      linking moderation to a negative social identity. The method employed in this
      study provided a frank insight into a student culture of intoxication and the
      barriers facing students who try to drink in moderation. Our findings reveal that
      limiting consumption, even occasionally, threatens students' social identity and
      inclusion in the student drinking culture. These results suggest that
      individualistic harm minimization strategies are unlikely to be effective.
      Instead, the findings underscore the need to develop alternative cultures
      emphasizing extracurricular activities which may facilitate students' agency to
      go against the norm and moderate their drinking.

PMID- 30093797
TI  - Is Procalcitonin Useful in Pediatric Critical Care Patients?
AB  - This review examines the use of procalcitonin in different clinical situations in
      the pediatric patient, with special emphasis on those requiring intensive care.
      We review the latest articles on its potency as a biomarker in both infectious
      processes at diagnosis and on the response to treatment.

PMID- 30093799
TI  - Effects of Resonance Voice Therapy on Hormone-Related Vocal Disorders in
      Professional Singers: A Pilot Study.
AB  - Background: Menstruation-related hormonal alteration can be detrimental to the
      professional singing voice of women. Resonance Voice Therapy (RVT) has been
      proven to improve vocal production. However, no research to date has been
      conducted examining the subjective, acoustic, and stroboscopic effects of RVT on
      professional female singers having premenstrual or postmenopausal voice
      disorders. Aim: The aim of this study is to compare the vocal effects of RVT with
      a control cervical-thoracic intervention in healthy female singers during the
      premenstrual phase as well as in postmenopausal singers and to evaluate which
      intervention will allow singers to improve vocal performance regardless of
      changes in hormonal status. Design: A randomized study was designed for this
      research. The research subjects were 20 professional female singers from the
      Southern California area, USA, with 10 premenstrual subjects in one group and 10
      postmenopausal subjects in the other group. Among each group, 5 subjects were
      randomly selected to receive RVT and the remaining subjects received cervical
      thoracic-focused exercises. The therapies consisted of 1 month of daily 15-minute
      sessions. For premenstrual subjects, voice data were collected at days 25 to 27
      of the premenstrual phase during a scheduled initial voice evaluation. Follow-up
      data were collected during the same phase of the menstrual cycle (days 25-27)
      after 1 month of exercises. For postmenopausal subjects, voice data were
      collected at an initial voice evaluation with follow-up after 1 month of the
      assigned voice treatment. Outcomes were assessed with the singer's voice handicap
      index (VHI), laryngeal videostroboscopic examination, maximum phonation time
      (MPT), relative average perturbation (RAP), and pitch range before and following
      completion of therapies. Alleviation or deterioration percentages were used for
      statistical analysis. Student t test was used for statistical comparison between
      therapies. Results: The RVT decreased singer's VHI for both premenstrual and
      postmenopausal subjects by an average of 67%, compared with 7.8% for the cervical
      thoracic therapy. The RVT also effectively decreased RAP by an average of 57%
      when combining the premenstrual and postmenopausal groups. The RVT increased MPT
      and pitch range among both premenstrual and postmenopausal subjects. The
      stroboscopic examination did not detect any significant differences between the 2
      interventions. Conclusions: The RVT is effective for professional female singers
      with hormone-related premenstrual and postmenopausal vocal changes. The RVT is
      suggested as one of the therapeutic approaches for vocal abnormalities in such a
      population. A larger cohort may be needed for future research. Level of Evidence:
      1b.

PMID- 30093801
TI  - Medico-legal aspect of dental practice.
AB  - Law influences every aspect of human activity, and dentistry in this regard is no
      exception. Ethical standards of the dental profession are seeing a steady
      decline, altruistic concepts being overridden by a market driven system. A
      deficient knowledge regarding the medico-legal aspects halts the effective
      implementation and delivery of efficient services. The review thus provides an
      overview of ethical standards, consents and their types, negligence,,
      determination of negligence, liabilities of dental practitioners and solicitors
      in dental practices, which comprehensively form an integral part of the medico
      legal aspect of dental practice.

PMID- 30093800
TI  - Early Clinical Outcomes, Patterns of Failure, and Acute Haematologic Toxicity of
      Image-Guided Volumetric Modulated Arc Therapy (IG-VMAT) in the Definitive
      Treatment of Locally Advanced Carcinoma Cervix.
AB  - Purpose: To evaluate clinical outcomes and failure patterns in patients with
      locally advanced cervical cancer (LACC) treated definitively using image-guided
      volumetric-modulated arc therapy (IG-VMAT). Methods and materials: This
      retrospective review included 18 consecutively treated patients with LACC.
      Treatment consisted of IG-VMAT and concurrent chemotherapy followed by
      intracavitary radiotherapy. The primary end points were overall survival (OS) and
      disease-free survival (DFS). Acute haematologic toxicity was evaluated using
      Radiation Therapy Oncology Group (RTOG) criteria. Results: A total of 16 patients
      were either stage IIB or IIIB and the median follow-up was 30.5 months
      (interquartile range: 13-36.25 months). The 2-year DFS was 63.3% (95% confidence
      interval [CI]: 52.8%-72.4%) and 2-year OS was 72.2% (95% CI: 62.1%-80.5%). There
      were 7 treatment failures, predominantly in-field. Acute haematologic toxicity
      was low. Conclusions: IG-VMAT is associated with favourable outcomes for patients
      with LACC.

PMID- 30093802
TI  - Fecal transplantation: digestive and extradigestive clinical applications.
AB  - Background and aim: Fecal transplantation or fecal material transplantation (FMT)
      became a hot topic in gastroenterology in recent years. Therefore it is important
      to disseminate the up-to-date information on FMT. The aim of the paper is to
      review the knowledge on FMT and its clinical applications. Methods: An extensive
      review of the literature was carried out. Titles from Pubmed were searched and
      analyzed. A narrative review has been written with emphasis on indications of FMT
      in different conditions. Results: The guidelines recommend FMT in relapsing
      infection with Clostridium difficile. Several attempts to use FMT in other
      conditions have been analyzed. Attempts were recorded in other bowel disorders
      like IBD, IBS, chronic constipation and even colorectal cancer. The attempt to
      change the microbiota by FMT in diabetes and obesity represent challenges for the
      future. Conclusions: Fecal transplantation represents an important therapeutic
      method, intensively investigated these years. Beside the indication for
      persistent and recurrent Clostridium difficile infection, several attempts were
      undertaken in other intestinal diseases and in metabolic conditions. The
      efficiency of these applications has to be demonstrated.

PMID- 30093803
TI  - Nurses and internet health-related information: review on access and utility.
AB  - Purpose: To review literature on the nurses' use and access to Internet Health
      Related Information (HRI). There is relatively little evidence in published
      literature on barriers, attitudes and how nurses utilize online health-related
      information. Methods: Literature search was carried-out on Cumulative Indexes to
      Nursing and Allied Health Literature (CINAHL), MEDLINE, Google Scholar, Springer
      and Sage publications. The search timeframe has focused on the outburst of
      Internet usage between the years 2000 and 2014. Results: Quality of available
      websites and databases containing health-related information vary widely in their
      accuracy, validity and reliability that require nurses to continuously evaluate
      their relevance. Conclusion: Emphasis on the necessity for training in the use of
      information technology is important to the nurses' continuous professional
      development. Literature showed a strong evidence of the increased access to the
      Internet by nurses to retrieve information related to clinical practice, which in
      turns enhance the quality of care and communication among nurses.

PMID- 30093806
TI  - Ferritin level changes and erythroid improvement in a group of adult
      polytransfused patients treated with Deferasirox.
AB  - Background and aims: Chelating agents therapy is recommended for polytransfused
      patients that have evidence of iron overload (an elevated serum ferritin or
      received over 20 units of red blood cell transfusions). Deferasirox showed
      efficacy and safety in maintaining or reducing body iron. Iron chelation therapy
      was associated with hematopoiesis improvement in transfusion-dependent
      patients.Our objectives were to analyze differences in ferritin level in adult
      polytransfused patients treated with Deferasirox, to estimate the erythroid
      improvement and variation of the number of red blood cell transfusion after
      introducing Deferasirox, to evaluate the side effects of the treatment. Methods:
      Retrospective study including all the adult polytransfused patients treated with
      Deferasirox in Hematology Departments of three county hospitals in the North-West
      of Romania. Results: We included 40 polytransfused patients treated with
      Deferasirox in standard doses. There was a significant reduction in serum
      ferritine from baseline for all the patients (Friedman test, chi2(2)=26.82,
      p<0.001). Safety profile of Deferasirox was good (three digestive side effects).
      RBCT were administered before (mean 2.43+/-1.09 units/month) and after starting
      Deferasirox (mean 1.40+/-0.97 units/month), the difference is statistically
      significant (Student Test, t(39)=6.98, p<0.001). Conclusions: Deferasirox proves
      to be an effective iron chelator, the serum level of ferritine decreased for all
      the patients during the treatment and 22.5 % of the patients developed an
      erythroid improvement. Safety and compliance were good.

PMID- 30093804
TI  - Current perspectives regarding the application and incorporation of silver
      nanoparticles into dental biomaterials.
AB  - Introduction: The key idea of nanotechnology is to construct and preserve
      functional structures by means of exploiting atoms and molecules. Nanotechnology
      has proven to be crucial in pharmacological medicine, tissue engineering,
      clinical diagnosis, long term conservation of biological tissues in a cryogenic
      state, protein detection, tumor destruction and magnetic resonance imaging.The
      aim of this paper is to review the literature on the specific characteristics of
      nanostructured materials, their applications and advantages that they bring to
      dentistry. Method: We conducted an electronic scientific database research that
      included PubMed, Cochrane and Medline. The following keywords were used:
      nanotechnology, nanodentistry and silver nanoparticles. Initially 1650 original
      articles were retrieved from the these mentioned international databases, which
      were screened in detail. We included literature reviews that dealt with the
      comprehensive applications of nanostructured particles and silver nanoparticles
      in particular, in all fields of contemporary dentistry. Case reports, clinical
      trials, editorials and opinion letters were excluded in the first phase of our
      research. Fifty two articles met all the selection criteria and were ultimately
      selected and reviewed. Results: Nanotechnology deals with the production of
      various types of nanomaterials with potential applications in the field of
      biomedicine. Silver nanoparticles have the capacity to eliminate dental caries
      producing bacteria or repair teeth enamel with signs of dental decay.
      Nanodentistry will allow better oral health by use of nanostructured materials.
      Treatment opportunities that nanotechnology has to offer in contemporary
      dentistry include local anesthesia, permanent treatment of dental
      hypersensitivity, orthodontic and oral health care with nanorobotic dentifrice.
      Conclusion: The studies that we reviewed are largely in favor of nanotechnology
      and nanostructured materials, highlighting their qualities and enhancements they
      bring to the field of dentistry. Although many of these products that benefit
      from silver nanoparticles properties are still expensive and exclusive, we can
      foresee major improvements and demand regarding dental biomaterials with
      nanoparticles incorporated in the near future.

PMID- 30093805
TI  - Imaging modalities for temporomandibular joint disorders: an update.
AB  - The diagnosis and management of temporomandibular disorders (TMD) require both
      clinical and imaging examinations of the temporomandibular joint (TMJ). A variety
      of modalities can be used to image the TMJ, including magnetic resonance imaging
      (MRI), computed tomography (CT), cone beam CT, ultrasonography, conventional
      radiography. The present review outlines the indications of the most frequently
      used imaging techniques in TMD diagnosis. Because of the anatomic complexity of
      the TMJ, imaging can be difficult. Choosing the proper imaging technique is
      essential. Conventional radiography, nowadays, is of limited interest. The use of
      flat plane films for TMJ pathology is not sufficient, because this joint requires
      three dimensional imaging views. Osseous changes are better visualized with CT
      and cone beam CT. Cone beam CT provides high-resolution multiplanar
      reconstruction of the TMJ, with a low radiation dose, without superimposition of
      the bony structures. MRI is a noninvasive technique, considered to be the gold
      standard in imaging the soft tissue components of the TMJ. MRI is used to
      evaluate the articular disc in terms of location and morphology. Moreover, the
      early signs of TMD and the presence of joint effusion can be determined. High
      resolution ultrasonography is a noninvasive, dynamic, inexpensive imaging
      technique, which can be useful in diagnosing TMJ disc displacements. The
      diagnostic value of high-resolution ultrasonography is strictly dependent on the
      examiner's skills and on the equipment used.

PMID- 30093807
TI  - Incidental findings during follow-up scans in oncological patients.
AB  - Background and aim: To assess the prevalence of incidental findings during follow
      up scans of patients with oncologic pathology. Methods: 499 follow-up scans from
      different patients with cancer pathology were retrospectively analyzed. Findings
      which were not suspected by the clinician or known from previous scans were
      considered as incidental lesions. We excluded lesions that were already suspected
      by the clinician or were already recorded in the patient's history before the
      initial computed tomography (CT) scan. The CT scans were performed on two
      different machines ("Siemens Somatom Sensation, 64 slices, Erlangen, Germany" and
      "Siemens Somatom Emotion, 16 slices, Erlangen, Germany").Most of the patients had
      a native scan followed by a thoraco-abdominal-pelvic image acquisition after the
      injection of intravenous contrast media. Results: 28% of the patients had
      unsuspected incidental findings. The prevalence of incidental findings was
      similar: 56.6% of them were found in men and 43.4% in female patients. In 6 cases
      (1.2%) the presence of unsuspected pulmonary embolism was discovered. From these
      cases, 5 (83.3%) had metastatic disease at the moment of the follow-up CT scan
      and 1 (16.6%) had metastasis-free disease. In 17 patients out of 499 (3.4%) we
      incidentally made an important discovery which either changed the cancer therapy
      or required immediate treatment. Conclusion: Incidental findings are not rare in
      oncological patients and the radiologist has to be aware of their presence in
      order not to overlook them and to correctly diagnose them.

PMID- 30093809
TI  - Improving communication within the interdisciplinary team monitoring young women
      with onco-gynecological pathology in Romania.
AB  - Background: The quality of medical care, as well as the application of effective
      treatments in the management of patients with gynecologic neoplasm, is of great
      importance. Finding new and efficient ways of communication between the doctors
      involved in the multidisciplinary team for the management of the disease, from
      the diagnosis to the reintegration into society, would help improve the quality
      of comprehensive patient care. Objective: The objective of the study was to
      assess the collaboration of family physicians with specialists treating patients
      suffering from gynecologic cancer, in order to improve the relationship between
      them via electronic communication. Study design: We conducted a descriptive,
      transversal study on 353 family physicians and 37 specialist doctors from
      Romania, between January and June 2015. For statistical data analysis, R for Data
      Analysis and Graphics version 3.2.1 was used. Results: Most of the family
      physicians and specialist doctors believed that they provided the best care that
      they could, but consider that a multidisciplinary approach using online
      communication methods, in which doctors collaborate among each other, is needed.
      Conclusions: Finding a simple, efficient and modern means of communication is
      essential in order to increase the efficiency of medical care overall.

PMID- 30093808
TI  - Relationship of internet addiction with depression and academic performance in
      Indian dental students.
AB  - Background and aims: Internet addiction (IA) has negative consequences on the
      mental health and affects daily activities. This study was conducted with the aim
      to assess the prevalence of Internet addiction among dental university students
      and to determine if there is any relationship of excessive Internet use with
      depression and academic performance among students. Methods: This was a cross
      sectional study which included 384 dental students from different academic years.
      A questionnaire was prepared that collected information on demographic
      characteristics, pattern of Internet use, duration of use, and most common mode
      of Internet access. Internet addiction was assessed using Youngs Internet
      Addiction test. Depression was assessed using Becks depression inventory [BDI-1].
      Results: The prevalence of Internet addiction and depression was found to be 6%
      and 21.5% respectively. The first year students showed the highest mean Internet
      addiction (17.42+/-12.40) score. Chatting was the main purpose for Internet use.
      Logistic regression analysis showed that individuals who were depressed (Odds
      Ratio=6.00, p value<0.0001*) and scored less than 60% marks (Odds Ratio=6.71, p
      value<0.0001*) were more likely to be addicted to Internet. Conclusion: The
      addiction to internet has negative impact on mental health and academic
      performance. These high risk group students should be identified and
      psychological counseling should be provided.

PMID- 30093810
TI  - Lifestyle and psychosocial factors in musicians.
AB  - Background and aim: Musicians face professional challenges that may lead them to
      adopt unhealthy lifestyles. They also may present performance-related anxiety. We
      investigated anxiety and lifestyle patterns in musicians, both professional and
      trainees. Methods: A prospective controlled protocol was developed. Musicians
      (employed or students) and matched controls (also employed and students) were
      surveyed with several questionnaires on lifestyle and some psychological factors:
      anxiety and music performance anxiety. Results: General anxiety and music
      performance anxiety are higher in music students compared with trained musicians.
      Musicians have also higher anxiety scores than their matched controls. Soloists
      have higher scores of anxiety, also percussion and keyboard students. Musicians
      smoke less than controls, but sleep also less, a factor perceived as an index for
      stress. BMI was also higher in musicians. Conclusions: Performing music is
      associated with anxiety levels that are higher than in control population.
      Trainees have higher scores than the employed musicians.

PMID- 30093811
TI  - Association between different blood groups, depression and oral health status of
      dental students.
AB  - Introduction: Knowledge of blood groups and their association with oral diseases
      and depression is very important, as it may help in early diagnosis and treatment
      strategies. Method: A cross sectional descriptive study was conducted among
      dental students of a private dental college. The study was conducted in two
      phases, in the first phase the blood samples of each student were collected and
      sent for blood group examination in laboratory. Data for oral health status was
      collected by recording oral hygiene, dental caries and questions regarding oral
      hygiene habits and adverse oral habits. Depression level was recorded using a pre
      validated, 21 item close ended questionnaire. Data thus collected was subjected
      to statistical analysis using chi-square and frequency distribution test using
      SPSS software. Results: The total study subjects were 315, 95 males and 220
      females. On applying chi-square test between blood group and Decayed, Missing and
      Filled Teeth (DMFT) score, a highly significant association (p=0.00) was
      observed. A non-significant association p=0.217 and p=0.668 was observed between
      gender and DMFT and Oral hygiene index-simplified and Blood group respectively.
      When comparing blood group and Depression score, a non-significant association
      (p=0.74) was observed. Conclusion: DMFT score varies in different blood groups
      and this might suggest a positive association between blood groups and DMFT
      score, while depression, oral hygiene and gender might not be affected by the
      different blood groups.

PMID- 30093812
TI  - Electrolyzed saline... an alternative to sodium hypochlorite for root canal
      irrigation.
AB  - Objectives: The aim of this study is to evaluate electrolyzed saline, produced
      from a custom-made chair side apparatus for its cleaning effect on root canal
      walls. Methods: A chair side apparatus has been designed to produce and dispense
      electrolytically activated solutions (Electrolyzed saline) for the purpose of
      root canal irrigation. Two different solutions, one, which is oxidizing in
      nature, consisting primarily of Chlorine derivatives and another, reducing in
      nature, consisting primarily of sodium hydroxide, are obtained. A combination of
      these two solutions was used for root canal irrigation in extracted teeth. Root
      canals were split and the samples were subjected to Scanning electron microscopic
      evaluation. Results: Under the conditions of this study, electrolyzed saline
      significantly cleaned the root canal surfaces well, opening the dentinal tubules
      and removing the smear layer. Significance: There has been a constant search for
      the ideal root canal irrigant. Sodium hypochlorite has been vastly used but its
      toxicity and storage risks are of concern. Electrolyzed saline has been produced
      from saline and the apparatus prepares and dispenses the solution chair side,
      obviating storage needs.

PMID- 30093813
TI  - Prevalence of traumatic dental injuries and their relation with predisposing
      factors among 8-15 years old school children of Indore city, India.
AB  - Background: Dental injuries result in functional, esthetic and psychological
      disturbances accompanied by great concern from the child, the parent and the
      dentist. Oral injuries are fourth most common area of bodily injuries among 7-30
      year-old individuals. Aim: a) To assess the prevalence of traumatic dental
      injuries (TDI) and their relation with predisposing factors among 8-15 years old
      school children in Indore city, India.b) To collect baseline data as there have
      been no reported studies of TDI in central India to this date. Methods: A cross
      sectional study was carried out among 4000 children of 60 schools in Indore using
      multistage random sampling method. Examination of permanent incisor teeth was
      done in accordance with the modified Elli's and Davey Classification using a
      standard mouth mirror and probe. Subjects who had clinical evidence of trauma
      were interviewed for details of the injury event by using structured
      questionnaire. Chi square test was used to analyze the distribution of all the
      measurement in this study at the statistical significance of 0.05. Results: Among
      the 4000 children of 60 schools examined, 10.2% experienced TDI. 68.38% boys
      experienced TDI, which was approximately twice as higher in females being 31.62%.
      The most commonly affected teeth were maxillary central incisors. A higher number
      of children with incisal overjet greater than 3 mm had TDI than those with less
      than 3 mm, although this difference was not statistically significant. Lip
      closure incompetence was found to be more common in subjects having a TDI. Fall
      was the most common cause for TDI and place of occurrence was home. Most common
      type of fracture was class I and most of them were untreated. Conclusion: The
      high level of dental trauma and low percentage of children with trauma seeking
      treatment stresses the need for increased awareness in Indore population.

PMID- 30093814
TI  - Psycho-social impact of orthodontic treatment in Romanian teenagers and young
      adults.
AB  - Background and aims: This survey evaluated the psycho-social impact of oral
      health on the quality of life in Romanian teenage and young adult orthodontic
      patients. Methods: Of the 300 standard questionnaires distributed in four dental
      offices, 125 questionnaires were returned. Each questionnaire contained 110
      items, focusing on aspects like patients' satisfaction, self-confidence,
      school/work performances and aesthetic concern, in relation to oral health. The
      patients were 16-25 years of age and all were undergoing or had undergone
      orthodontic treatment in the previous two years. Data analysis was performed
      using the Statistical Package for the Social Science software (SPSS), version
      19.0. Results: 57.90% of the orthodontic patients participating in this study
      were happy about their dental status, 56.52% declared themselves not shy because
      of their oral health issues, 52.33% considered themselves as attractive to other
      people, and 57.29% replied (awarding a score between 8 and 10) that they were
      confident when smiling. Regarding self-confidence and school/work performances,
      58% of the participants declared they avoided speaking in public because of the
      aspect of their teeth and 47.42% considered that their school/work performances
      during the fix appliance therapy stayed the same as before appliance.
      Nevertheless, the self-perceived facial aspect improved during orthodontic
      treatment (64.74% of replies had scores between 8 and 10 during the treatment
      versus 24.67% before the treatment). Several correlations were found between
      aspects such as psycho-social and functional variables, physical self-evaluation,
      and oral health issues. Conclusion: Patients' satisfaction was improved during
      and after appliance therapy, for more than half of the participants. Self
      confidence was low in relation to school/work performances; almost half of the
      patients reported stagnation in their school/work performances during the fix
      appliance therapy. However, more than 64% of the patients participating in this
      study were quite satisfied about their facial aspect during and after the
      orthodontic treatment. Thus, the common concerns of the patients anxious about
      their aspect during appliance therapy are not supported by the findings of this
      study.

PMID- 30093815
TI  - Atrioventricular conduction defect associated with severe hyponatremia.
AB  - Hyponatremia is the most common electrolyte disorder among hospitalized patients
      and in the clinical setting. Patients with hyponatremia may develop a variety of
      symptoms, primarily neurological and gastrointestinal. Hyponatremia is more
      frequently encountered in patients with an underlying heart disease, particularly
      in the elderly. We hereby present a case of complete atrioventricular block in an
      elderly patient who had undergone aortic valve replacement and had been using
      thiazide. Complete atrioventricular block improved after sodium replacement
      therapy and no other cause of electrolyte disorder was documented.

PMID- 30093816
TI  - Retroperitoneal laparoendoscopic single-site approach for renal cyst
      decortication - first experience and a review of literature.
AB  - Laparoendoscopic single-site (LESS) approach has been successfully employed for a
      number of urologic procedures. The retroperitoneal approach further limits the
      working space and instrument movement during LESS surgery, but has the advantage
      of a faster post-operative recovery and lower complications rate. We present our
      first experience using retroperitoneal LESS approach for a renal cyst
      decortication in a 40-year-old patient. The operative time was 40 minutes, the
      blood loss was minimal and we did not encounter significant conflicts between the
      instruments. The patient was discharged 2 days after the procedure and returned
      to full normal activity within one week. We consider that the retroperitoneal
      LESS approach is feasible for upper tract urologic surgery. Pre-bent instruments
      might further improve surgical gestures and extend the indications for more
      complex procedures. Nevertheless, the advent of reusable devices is expected to
      increase the cost-effectiveness of LESS and expand its use.

PMID- 30093817
TI  - Cutaneous dental sinus of submental region: an eight years follow-up.
AB  - A 22-year-old female patient had a history of a 7-month recurrent pus discharge
      from her chin. She had been previously treated by physicians, dermatologist, and
      surgeons. The sinus kept re-occurring and she was referred to dental hospital for
      opinion. The patient had cutaneous opening of size 5 mm * 6 mm with purulent
      discharge in submental region. Patient had undergone three surgical excisions and
      multiple antibiotic regimens. Patient had a history of trauma due to fall six
      years back. A 30 number standard gutta-percha was used to trace the sinus tract
      and dental origin was confirmed radiographically. The tract led to in-between the
      root canal apices of both mandibular incisors. Treatment included non-surgical
      endodontic treatment with both mandibular central incisors and antibiotic
      coverage following bacterial culture of discharge. The pus culture showed
      Streptococcus anginosus which was found to be sensitive to penicillin. Patient
      was kept on 1-week course of oral amoxicillin-clavulanate along with root canal
      therapy. The cutaneous sinus healed following root canal treatment and antibiotic
      coverage. On an 8-year follow-up skin of sub-mental region appeared normal and
      peri-apical healing with both mandibular central incisors was evident
      radiographically. Cutaneous lesions on face may be of dental origin. A cross
      referral between dentists, physicians, surgeons, and dermatologists should be
      considered in such cases.

PMID- 30093818
TI  - Gheorghe Barlea MD, PhD, pupil and collaborator of Professor Bilascu.
AB  - Being the first collaborator and assistant of Professor Gheorghe Bilascu, the
      founder of Cluj and National School of Dentistry, Dr. Gheorghe Barlea kept very
      close to his master in developing the Dental Medicine in Cluj and in Romania,
      from 1908 to 1936. From the beginning of his career, he was involved in the
      establishment of the new Dental Clinic in the University of Superior Dacia as
      well as in the compilation of the teaching curriculum at the level of the avant
      garde universities at that time. He was deeply involved in the recognition of
      Dentistry as discipline and medical practice and in the official achievement of
      the law and practice of this profession in Romania. Dr. Barlea devoted his life
      and wotk to the cultural and social life of the Romanians, his efforts
      contributing to the Great Union of Romania. Passing away at an early age, Dr.
      Barlea left Romanian dental profession without an important support.

PMID- 30093820
TI  - Assessing high-impact spots of climate change: spatial yield simulations with
      Decision Support System for Agrotechnology Transfer (DSSAT) model.
AB  - Drybeans (Phaseolus vulgaris L.) are an important subsistence crop in Central
      America. Future climate change may threaten drybean production and jeopardize
      smallholder farmers' food security. We estimated yield changes in drybeans due to
      changing climate in these countries using downscaled data from global circulation
      models (GCMs) in El Salvador, Guatemala, Honduras, and Nicaragua. We generated
      daily weather data, which we used in the Decision Support System for
      Agrotechnology Transfer (DSSAT) drybean submodel. We compared different
      cultivars, soils, and fertilizer options in three planting seasons. We analyzed
      the simulated yields to spatially classify high-impact spots of climate change
      across the four countries. The results show a corridor of reduced yields from
      Lake Nicaragua to central Honduras (10-38 % decrease). Yields increased in the
      Guatemalan highlands, towards the Atlantic coast, and in southern Nicaragua (10
      41 % increase). Some farmers will be able to adapt to climate change, but others
      will have to change crops, which will require external support. Research
      institutions will need to devise technologies that allow farmers to adapt and
      provide policy makers with feasible strategies to implement them.

PMID- 30093819
TI  - Mothers' Opisthorchis viverrini infection status and raw fish dish consumption in
      Lao People's Democratic Republic: determinants of child infection status.
AB  - Background: Opisthorchis viverrini (Ov) infection is one of the foodborne
      trematodiases, which is highly endemic in Lao People's Democratic Republic (PDR).
      The infection occurs especially when people eat raw fish containing Ov
      metacercariae. As eating raw fish is a traditional culture in Lao PDR, changing
      this behavior is difficult. A new approach is necessary to control Ov infection
      because people easily get re-infected even after taking praziquantel unless they
      change their behaviors. This study aimed to explore factors associated with Ov
      infection among children and to identify the existing behaviors and perception
      that might contribute to the control of Ov infection in Lao PDR. We conducted a
      cross-sectional study in Yommalath district, Khammouane province, in Lao PDR in
      August and September 2015. In this cross-sectional study, we used a semi
      structured questionnaire and interviewed 348 mothers who had a child aged 5-15
      years. We also collected the fecal samples from each mother-child pair and used
      the Kato-Katz method (three slides/sample) to detect Ov eggs. Results: Of 284
      children, 82.8% were infected with Ov. The children were more likely to be
      infected with Ov when their mothers were infected with Ov (adjusted odds ratio
      [AOR] 10.45, 95% confidence interval [CI] 3.13-34.86) or when their mothers liked
      raw fish dishes (AOR 2.47, 95% CI 1.07-5.69). Even though most mothers are
      primarily in charge of cooking family meals, fathers were also involved in the
      preparation of raw fish dishes. Conclusion: This study suggests that a new
      approach to control Ov infection should target families or communities, rather
      than children only. Cooking or food preparation behaviors should be investigated
      in more depth.

PMID- 30093821
TI  - From site-level to regional adaptation planning for tropical commodities: cocoa
      in West Africa.
AB  - The production of tropical agricultural commodities, such as cocoa (Theobroma
      cacao) and coffee (Coffea spp.), the countries and communities engaged in it, and
      the industries dependent on these commodities, are vulnerable to climate change.
      This is especially so where a large percentage of the global supply is grown in a
      single geographical region. Fortunately, there is often considerable spatial
      heterogeneity in the vulnerability to climate change within affected regions,
      implying that local production losses could be compensated through
      intensification and expansion of production elsewhere. However, this requires
      that site-level actions are integrated into a regional approach to climate change
      adaptation. We discuss here such a regional approach for cocoa in West Africa,
      where 70 % of global cocoa supply originates. On the basis of a statistical model
      of relative climatic suitability calibrated on West African cocoa farming areas
      and average climate projections for the 2030s and 2050s of, respectively, 15 and
      19 Global Circulation Models, we divide the region into three adaptation zones:
      (i) a little affected zone permitting intensification and/or expansion of cocoa
      farming; (ii) a moderately affected zone requiring diversification and agronomic
      adjustments of farming practices; and (iii) a severely affected zone with need
      for progressive crop change. We argue that for tropical agricultural commodities,
      larger-scale adaptation planning that attempts to balance production trends
      across countries and regions could help reduce negative impacts of climate change
      on regional economies and global commodity supplies, despite the institutional
      challenges that this integration may pose.

PMID- 30093822
TI  - Impacts of land use, restoration, and climate change on tropical peat carbon
      stocks in the twenty-first century: implications for climate mitigation.
AB  - The climate mitigation potential of tropical peatlands has gained increased
      attention as Southeast Asian peatlands are being deforested, drained and burned
      at very high rates, causing globally significant carbon dioxide (CO2) emissions
      to the atmosphere. We used a process-based dynamic tropical peatland model to
      explore peat carbon (C) dynamics of several management scenarios within the
      context of simulated twenty-first century climate change. Simulations of all
      scenarios with land use, including restoration, indicated net C losses over the
      twenty-first century ranging from 10 to 100 % of pre-disturbance values. Fire can
      be the dominant C-loss pathway, particularly in the drier climate scenario we
      tested. Simulated 100 years of oil palm (Elaeis guineensis) cultivation with an
      initial prescribed burn resulted in 2400-3000 Mg CO2 ha-1 total emissions.
      Simulated restoration following one 25-year oil palm rotation reduced total
      emissions to 440-1200 Mg CO2 ha-1, depending on climate. These results suggest
      that even under a very optimistic scenario of hydrological and forest restoration
      and the wettest climate regime, only about one third of the peat C lost to the
      atmosphere from 25 years of oil palm cultivation can be recovered in the
      following 75 years if the site is restored. Emissions from a simulated land
      degradation scenario were most sensitive to climate, with total emissions ranging
      from 230 to 10,600 Mg CO2 ha-1 over 100 years for the wettest and driest dry
      season scenarios, respectively. The large difference was driven by increased fire
      probability. Therefore, peat fire suppression is an effective management tool to
      maintain tropical peatland C stocks in the near term and should be a high
      priority for climate mitigation efforts. In total, we estimate emissions from
      current cleared peatlands and peatlands converted to oil palm in Southeast Asia
      to be 8.7 Gt CO2 over 100 years with a moderate twenty-first century climate.
      These emissions could be minimized by effective fire suppression and hydrological
      restoration.

PMID- 30093823
TI  - A methodological framework to operationalize climate risk management: managing
      sovereign climate-related extreme event risk in Austria.
AB  - Despite considerable uncertainties regarding the exact contribution of
      anthropogenic climate change to disaster risk, rising losses from extreme events
      have highlighted the need to comprehensively address climate-related risk. This
      requires linking climate adaptation to disaster risk management (DRM), leading to
      what has been broadly referred to as climate risk management (CRM). While this
      concept has received attention in debate, important gaps remain in terms of
      operationalizing it with applicable methods and tools for specific risks and
      decision-contexts. By developing and applying a methodological approach to CRM in
      the decision context of sovereign risk (flooding) in Austria we test the
      usefulness of CRM, and based on these insights, inform applications in other
      decision contexts. Our methodological approach builds on multiple lines of
      evidence and methods. These comprise of a broad stakeholder engagement process,
      empirical analysis of public budgets, and risk-focused economic modelling. We
      find that a CRM framework is able to inform instrumental as well as reflexive and
      participatory debate in practice. Due to the complex interaction of social
      ecological systems with climate risks, and taking into account the likelihood of
      future contingent climate-related fiscal liabilities increasing substantially as
      a result of socioeconomic developments and climate change, we identify the need
      for advanced learning processes and iterative updates of CRM management plans. We
      suggest that strategies comprising a portfolio of policy measures to reduce and
      manage climate-related risks are particularly effective if they tailor individual
      instruments to the specific requirements of different risk layers.

PMID- 30093824
TI  - The effect of increasing lifespan and recycling rate on carbon storage in wood
      products from theoretical model to application for the European wood sector.
AB  - The use of wood products is often promoted as a climate change mitigation option
      to reduce atmospheric carbon dioxide concentrations. In previous literature, we
      identified longevity and recycling rate as two determining factors that influence
      the carbon stock in wood products, but no studies have predicted the effect of
      improved wood use on carbon storage over time. In this study, we aimed at
      evaluating changes in the lifespan and the recycling rate as two options for
      enhancing carbon stock in wood products for different time horizons. We first
      explored the behaviour over time of both factors in a theoretical simulation, and
      then calculated their effect for the European wood sector of the future. The
      theoretical simulation shows that the carbon stock in wood products increases
      linearly when increasing the average lifespan of wood products and exponentially
      when improving the recycling rate. The emissions savings under the current use of
      wood products in Europe in 2030 were estimated at 57.65 Mt carbon dioxide (CO2)
      per year. This amount could be increased 5 Mt CO2 if average lifespan increased
      19.54 % or if recycling rate increased 20.92 % in 2017. However, the combination
      of both strategies could increase the emissions saving almost 5 Mt CO2 more by
      2030. Incrementing recycling rate of paper and paperboard is the best short-term
      strategy (2030) to reduce emissions, but elongating average lifespan of wood
      based panels is a better strategy for longer term periods (2046).

PMID- 30093825
TI  - Evaluating multiple emission pathways for fixed cumulative carbon dioxide
      emissions from global-scale socioeconomic perspectives.
AB  - Recent climate modeling studies have concluded that cumulative carbon emissions
      determine temperature increase, regardless of emission pathways. Accordingly, the
      optimal emission pathway can be determined from a socioeconomic standpoint. To
      access the path dependence of socioeconomic impacts for cumulative carbon
      emissions, we used a computable general equilibrium model to analyze impacts on
      major socioeconomic indicators on a global scale for 30-50 pathways with
      different emission reduction starting years, different subsequent emission
      pathways, and three different cumulative 2100 emission scenarios (emissions that
      meet the 2  degrees C target, the 2  degrees C target emissions plus 10 %, and
      emissions producing radiative forcing of 4.5 W/m2). The results show that even
      with identical cumulative emission figures, the resulting socioeconomic impacts
      vary by the pathway realized. For the United Nations 2  degrees C target, for
      example, (a) the 95 % confidence interval of cumulative global gross domestic
      product (GDP) is 1355-1363 trillion US dollars (2010-2100, discount rate = 5 %),
      (b) the cumulative GDP of pathways with later emission reduction starting years
      grows weaker (5 % significance level), and (c) emissions in 2100 have a moderate
      negative correlation with cumulative GDP. These results suggest that GDP loss is
      minimized with pathways with earlier emission reduction followed by more moderate
      reduction rates to achieve lower emission levels. Consequently, we suggest an
      early emission peak to meet the stringent target. In our model setting, it is
      desirable for emissions to peak by 2020 to reduce mitigation cost and by 2030 at
      the latest to meet the 2  degrees C target.

PMID- 30093826
TI  - Gaps in the capacity of modern forage crops to adapt to the changing climate in
      northern Europe.
AB  - The within-species diversity in response to weather and the gaps in the response
      diversity in the modern set of forage crop cultivars were determined using an
      approach that assessed the adaptive capacity under global climate change. The
      annual dry matter (DM) yields were recorded in multi-location MTT (Maa- ja
      elintarviketalouden tutkimuskeskus) Agrifood Research Official Variety Trials in
      Finland for modern forage crop cultivars from 2000 to 2012, as a response to
      agroclimatic variables critical to yield based on the year-round weather data.
      The effect and interaction of cultivars and agroclimatic variables were analysed
      using mixed model. The relatively low adaptive capacity of timothy (Phleum
      pratense L.) and meadow fescue (Festuca pratensis Huds.) indicates that
      diversification of the breeding material is warranted, particularly for
      resistance to high temperatures during primary growth and to high temperature sum
      7 days after the first cut. All red clover cultivars (Trifolium pratense L.)
      suffered from both low and high accumulation of warm winter temperatures. Except
      for the red clover cultivars, cold stress during winter and lack of warm winter
      temperatures consistently reduced the yields of all species and cultivars. All
      tall fescue (Festuca arundinacea Schreb.) cultivars suffered from low
      precipitation during the fall hardening period. Although the set of festulolium
      (Festulolium pabulare) cultivars was also sensitive to low precipitation during
      the fall, festulolium was a good example of enhanced capacity to adapt to climate
      change with high response diversity because the cultivar germplasm base was
      diversified. Foreign origin in a cultivar pool was apparently not sufficient or
      necessary to ensure added value for a diversity of responses to climate change.
      Similar analyses to those used in this study, applied as practical tools for
      breeders, farmers and public actors, are important to secure the adaptive
      capacity of crops worldwide under global climate change.

PMID- 30093827
TI  - Flood protection and endogenous sorting of households: the role of credit
      constraints.
AB  - Human migration is increasingly seen as a promising climate change adaptation and
      flood risk reduction strategy. The purpose of this paper is to investigate how
      spatial differences in flood risk, due to differences in flood protection, reduce
      the mobility of vulnerable households through a credit constraint mechanism.
      Using an equilibrium model with two households types and endogenous sorting, we
      show how spatial differences in flood protection lead to clustering of vulnerable
      households in a risky region, in a real-world setting of common United States
      (US) flood zones. We find clustering effects of some size for flood zones with
      return periods of less than 30 years.

PMID- 30093828
TI  - Urban heat indicator map for climate adaptation planning.
AB  - By 2050, 75 % of the world's population will live in cities and the occurrence of
      heat wave events might have doubled. Mapping the climate and land use change
      impact for urban heat events should set the agenda for adaptation planning at the
      local scale. Literature on urban heat mapping does not reveal a clear indicator
      to visualise the urban heat impacts that includes consequences of land use and
      climate changes for planning purposes. This paper introduces a stepwise approach
      to develop a single complex indicator to map the urban heat impact for local
      climate adaptation planning processes. Information on climatic drivers and land
      use characteristics are combined and projected for future land use and climate
      change impacts. Next, several visualisation techniques are developed to
      investigate which techniques are most effective to visualise complex information
      with multiple variables in one visualisation. A usability test is performed to
      investigate how indicator and map meet the information and communication needs of
      policy makers. Our findings reveal that it is important to add information on
      future impacts to set the agenda for adaptation planning at the local scale.
      Applying cartographic techniques in a map series presentation has proven to be
      effective to map complex information in a single image and fulfil most of the
      identified information needs. Based on our finding, we introduce the information
      enrichment chain as a promising approach to support local adaptation planning.

PMID- 30093829
TI  - Towards a framework to assess, compare and develop monitoring and evaluation of
      climate change adaptation in Europe.
AB  - Adaptation is increasingly recognised as essential when dealing with the adverse
      impacts of climate change on societies, economies and the environment. However,
      there is insufficient information about the effectiveness of adaption policies,
      measures and actions. For this reason, the establishment of monitoring programmes
      is considered to be necessary. Such programmes can contribute to knowledge,
      learning and data to support adaptation governance. In the European Union (EU),
      member states are encouraged to develop National Adaptation Strategies (NASs).
      The NASs developed so far vary widely because of differing views, approaches and
      policies. A number of member states have progressed to monitoring and evaluating
      the implementation of their NAS. It is possible to identify key elements in these
      monitoring programmes that can inform the wider policy learning process. In this
      paper, four generic building blocks for creating a monitoring and evaluation
      programme are proposed: (1) definition of the system of interest, (2) selection
      of a set of indicators, (3) identification of the organisations responsible for
      monitoring and (4) definition of monitoring and evaluation procedures. The
      monitoring programmes for NAS in three member states-Finland, the UK and Germany
      were analysed to show how these elements have been used in practice, taking into
      account their specific contexts. It is asserted that the provision of a common
      framework incorporating these elements will help other member states and
      organisations within them in setting up and improving their adaptation monitoring
      programmes.

PMID- 30093830
TI  - Indonesia's forest conversion moratorium assessed with an agent-based model of
      Land-Use Change and Ecosystem Services (LUCES).
AB  - The Indonesian government recently confirmed its Intended Nationally Determined
      Contributions (INDCs) to mitigate global climate change. A forest moratorium
      policy that protects forest and peatland is a significant part of the INDCs;
      however, its effectiveness is unclear in the face of complex land-use and land
      cover change. This study aims to assess the dynamics of land-use change and
      ecosystem service supply as a function of local decision-making. We developed an
      agent-based model, Land-Use Change and Ecosystem Services (LUCES), and used it to
      explore the possible effects of the forest moratorium policy on the land-use
      decisions of private companies and communities. Our simulations for two districts
      in Central Kalimantan show that the current implementation of the forest
      moratorium policy is not effective in reducing forest conversion and carbon
      emissions. This is because companies continue to invest in converting secondary
      forest on mineral soils and the moratorium does not affect community decision
      making. A policy that combines a forest moratorium with livelihood support and
      increases farm-gate prices of forest and agroforestry products could increase the
      local communities' benefits from conservation. Forest and agroforestry areas that
      are profitable and competitive are more likely to be conserved and reduce
      potential carbon emission by about 36 %. The results for the two districts, with
      different pressures on local resources, suggest that appropriate additional
      measures require local fine-tuning. The LUCES model could be an ex ante tool to
      facilitate such fine-tuning and help the Indonesian government achieve its INDC
      goals as part of a wider sustainable development policy.

PMID- 30093831
TI  - Climate change mitigation strategies in the forest sector: biophysical impacts
      and economic implications in British Columbia, Canada.
AB  - Managing forests to increase carbon sequestration or reduce carbon emissions and
      using wood products and bioenergy to store carbon and substitute for other
      emission-intensive products and fossil fuel energy have been considered effective
      ways to tackle climate change in many countries and regions. The objective of
      this study is to examine the climate change mitigation potential of the forest
      sector by developing and assessing potential mitigation strategies and portfolios
      with various goals in British Columbia (BC), Canada. From a systems perspective,
      mitigation potentials of five individual strategies and their combinations were
      examined with regionally differentiated implementations of changes. We also
      calculated cost curves for the strategies and explored socio-economic impacts
      using an input-output model. Our results showed a wide range of mitigation
      potentials and that both the magnitude and the timing of mitigation varied across
      strategies. The greatest mitigation potential was achieved by improving the
      harvest utilization, shifting the commodity mix to longer-lived wood products,
      and using harvest residues for bioenergy. The highest cumulative mitigation of
      421 MtCO2e for BC was estimated when employing the strategy portfolio that
      maximized domestic mitigation during 2017-2050, and this would contribute 35% of
      BC's greenhouse gas emission reduction target by 2050 at less than $100/tCO2e and
      provide additional socio-economic benefits. This case study demonstrated the
      application of an integrated systems approach that tracks carbon stock changes
      and emissions in forest ecosystems, harvested wood products (HWPs), and the
      avoidance of emissions through the use of HWPs and is therefore applicable to
      other countries and regions.

PMID- 30093832
TI  - Beyond opportunity costs: who bears the implementation costs of reducing
      emissions from deforestation and degradation?
AB  - Reducing Emissions from Deforestation and Degradation (REDD+) in developing
      countries is based on the premise that conserving tropical forests is a cost
      effective way to reduce carbon emissions and therefore can be fully funded by
      international actors with obligations or interests in reducing emissions.
      However, concerns have repeatedly been raised about whether stakeholders in REDD+
      host countries will actually end up bearing the costs of REDD+. Most prior
      analyses of the costs of REDD+ have focused on the opportunity costs of foregone
      alternative uses of forest land. We draw on a pan-tropical study of 22
      subnational REDD+ initiatives in five countries to explore patterns in
      implementation costs, including which types of organizations are involved and
      which are sharing the costs of implementing REDD+. We find that many
      organizations involved in the implementation of REDD+, particularly at the
      subnational level and in the public sector, are bearing implementation costs not
      covered by the budgets of the REDD+ initiatives. To sustain this level of cost
      sharing, REDD+ must be designed to deliver local as well as global forest
      benefits.

PMID- 30093833
TI  - Major challenges of integrating agriculture into climate change mitigation policy
      frameworks.
AB  - Taking the European Union (EU) as a case study, we simulate the application of
      non-uniform national mitigation targets to achieve a sectoral reduction in
      agricultural non-carbon dioxide (CO2) greenhouse gas (GHG) emissions. Scenario
      results show substantial impacts on EU agricultural production, in particular,
      the livestock sector. Significant increases in imports and decreases in exports
      result in rather moderate domestic consumption impacts but induce production
      increases in non-EU countries that are associated with considerable emission
      leakage effects. The results underline four major challenges for the general
      integration of agriculture into national and global climate change mitigation
      policy frameworks and strategies, as they strengthen requests for (1) a targeted
      but flexible implementation of mitigation obligations at national and global
      level and (2) the need for a wider consideration of technological mitigation
      options. The results also indicate that a globally effective reduction in
      agricultural emissions requires (3) multilateral commitments for agriculture to
      limit emission leakage and may have to (4) consider options that tackle the
      reduction in GHG emissions from the consumption side.

PMID- 30093834
TI  - Subsistence over symbolism: the role of transnational municipal networks on
      cities' climate policy innovation and adoption.
AB  - Urban areas account for the majority of global greenhouse gas emissions, and
      increasingly, it is city governments that are adopting and implementing climate
      mitigation policies. Many municipal governments have joined two different global
      city networks that aim to promote climate policy development at the urban scale,
      and there is qualitative evidence that such networks play an important role in
      motivating cities to adopt climate policies and helping them to implement them.
      Our study objective is to test this proposition quantitatively, making use of a
      global database on cities' environmental policy adoption, and also taking into
      account a large number of other factors that could play a role in climate policy
      adoption. Controlling for these other factors, we find that network membership
      does make a significant difference in the number of different measures that city
      governments adopt. We also find that there are significant differences between
      the two different networks, suggesting that the nature of the services that such
      networks offer their members can play an important role. Our findings lead to the
      provision of a set of global mitigation strategies: First of all, joining the
      city networks can lead to a generation of global strategies which can result into
      climate mitigation benefits. However, cities are required to select the network
      which provides proper tailor made policies. Second, in the absence of concrete
      international commitments at the local level, city networks lay the ground for
      global governance and enable cities to adopt policies independently and
      proactively. Third, consideration of co-benefits of climate policies can optimize
      the development of global strategies.

PMID- 30093835
TI  - Identifying high-yield low-emission pathways for the cereal production in South
      Asia.
AB  - Increasing agricultural production to meet the growing demand for food whilst
      reducing agricultural greenhouse gas (GHG) emissions is the major challenge under
      the changing climate. To develop long-term policies that address these
      challenges, strategies are needed to identify high-yield low-emission pathways
      for particular agricultural production systems. In this paper, we used bio
      physical and socio-economic models to analyze the impact of different management
      practices on crop yield and emissions in two contrasting agricultural production
      systems of the Indo-Gangetic Plain (IGP) of India. The result revealed the
      importance of considering both management and socio-economic factors in the
      development of high-yield low-emission pathways for cereal production systems.
      Nitrogen use rate and frequency of application, tillage and residue management
      and manure application significantly affected GHG emissions from the cereal
      systems. In addition, various socio-economic factors such as gender, level of
      education, training on climate change adaptation and mitigation and access to
      information significantly influenced the adoption of technologies contributing to
      high-yield low-emission pathways. We discussed the policy implications of these
      findings in the context of food security and climate change.

PMID- 30093836
TI  - Climate change control: the Lindahl solution.
AB  - The main purpose of this paper is to evaluate different burden sharing rules with
      respect to abatement of carbon emissions. We evaluate seven different rules both
      in terms of their redistributive impact and by the extent to which they realize
      the aim of optimal abatement. We show that the Lindahl solution, where the burden
      sharing rule of carbon abatement is determined by each region's willingness to
      pay, is to be preferred above the non-cooperative Nash outcome. Poor regions
      however would prefer the social planner outcome with a global permit market,
      because then the burden sharing rule has a secondary role of income
      redistribution by means of transfers from rich to poor, on top of its primary
      role of assigning abatement burdens. Based on these findings, we argue that in
      order to control global greenhouse gas emissions, the level of individual country
      emission abatement effort should be a function of their willingness to pay to
      curb climate change, rather than their historical emissions or ability to abate.

PMID- 30093837
TI  - Adaptation of land management in the Mediterranean under scenarios of irrigation
      water use and availability.
AB  - Meeting the growing demand for food in the future will require adaptation of
      water and land management to future conditions. We studied the extent of
      different adaptation options to future global change in the Mediterranean region,
      under scenarios of water use and availability. We focused on the most significant
      adaptation options for semiarid regions: implementing irrigation, changes to
      cropland intensity, and diversification of cropland activities. We used
      Conversion of Land Use on Mondial Scale (CLUMondo), a global land system model,
      to simulate future change to land use and land cover, and land management. To
      take into account future global change, we followed global outlooks for future
      population and climate change, and crop and livestock demand. The results
      indicate that the level of irrigation efficiency improvement is an important
      determinant of potential changes in the intensity of rain-fed land systems. No or
      low irrigation efficiency improvements lead to a reduction in irrigated areas,
      accompanied with intensification and expansion of rain-fed cropping systems. When
      reducing water withdrawal, total crop production in intensive rain-fed systems
      would need to increase significantly: by 130% without improving the irrigation
      efficiency in irrigated systems and by 53% under conditions of the highest
      possible efficiency improvement. In all scenarios, traditional Mediterranean
      multifunctional land systems continue to play a significant role in food
      production, especially in hosting livestock. Our results indicate that
      significant improvements to irrigation efficiency with simultaneous increase in
      cropland productivity are needed to satisfy future demands for food in the
      region. The approach can be transferred to other similar regions with strong
      resource limitations in terms of land and water.

PMID- 30093839
TI  - Tryptase as a marker of severity of aortic valve stenosis.
AB  - Background: Severe aortic valve stenosis is one of the most common cause of
      mortality in adult patients affected with metabolic syndrome, a condition
      associated with an active inflammatory process involving also mast cells and
      their mediators, in particular tryptase. The aim of this study was to
      characterize the possible long-term prognostic role of tryptase in severe aortic
      valve stenosis. Case presentation: The baseline serum tryptase was measured in 5
      consecutive patients admitted to our Hospital to undergo aortic valve replacement
      for severe acquired stenosis. Within 2 years after, the patients were evaluated
      for the occurrence of major cardiovascular events (MACE). The tryptase
      measurements were higher in patients experiencing MACE (10.9, 11.7 and 9.32
      ng/ml) than in non-MACE ones (5.69 and 5.58 ng/ml). Conclusions: In patients
      affected with severe aortic stenosis, baseline serum tryptase may predict
      occurence of MACE. Further studies are needed to demonstrate the long-term
      prognostic role of this biomarker.

PMID- 30093840
TI  - Targeting of HER3 with Functional Cooperative miRNAs Enhances Therapeutic
      Activity in HER2-Overexpressing Breast Cancer Cells.
AB  - Background: The HER3 receptor functions as a major cause of drug resistance in
      cancer treatment. It is believed that therapeutic targeting of HER3 is required
      to improve patient outcomes. It is not clear whether a novel strategy with two
      functional cooperative miRNAs would effectively inhibit erbB3 expression and
      potentiate the anti-proliferative/anti-survival effects of a HER2-targeted
      therapy (trastuzumab) and chemotherapy (paclitaxel) on HER2-overexpressing breast
      cancer cells. Results: Combination of miR-125a and miR-205, as compared to either
      miRNA alone, potently inhibited expression of HER3 in HER2-overexpressing breast
      cancer BT474 cells. Co-expression of the two miRNAs not only reduced the levels
      of phosphorylated erbB3 (P-erbB3), Akt (P-Akt), and Src (P-Src), it also
      inhibited cell proliferation and increased cells at G1 phase. A multi-miRNA
      lentiviral vector - the cluster of miR-125a and miR-205 - was constructed to
      simultaneously express the two miRNAs in HER2-overexpressing breast cancer cells.
      Concurrent expression of miR-125a and miR-205 via the miRNA cluster transfection
      significantly enhanced trastuzumab-mediated growth inhibition and cell cycle G1
      arrest in BT474 cells and markedly increased paclitaxel-induced apoptosis in
      another HER2-overexpressing breast cancer cell line HCC1954. Conclusions: Here,
      we showed that functional cooperative miRNAs effectively suppressed erbB3
      expression. This novel approach targeting of HER3 was able to enhance the
      therapeutic efficacy of trastuzumab and paclitaxel against HER2-overexpressing
      breast cancer.

PMID- 30093838
TI  - Clinicopathological and prognostic significance of long noncoding RNA MALAT1 in
      human cancers: a review and meta-analysis.
AB  - Background: The aberrant regulation of MALAT1 has been indicated to be involved
      in various carcinogenic pathways contributing to the tumourigenesis and
      progression of cancers. The current meta-analysis summarized the research
      advances of MALAT1 functions and analyzed its prognostic value among multiple
      types of cancers. Methods: Eligible studies were identified through retrieving
      the PubMed, Web of Science, and CNKI databases, up to Mar 1, 2018. 28 studies of
      5436 patients and 36 studies of 3325 patients were enrolled in the meta-analysis
      to evaluate the association of MALAT1 expression with survival outcomes and
      clinical parameters. Results: The results demonstrated that over-expression of
      MALAT1 may predict lymph node metastasis (pooled OR = 2.335, 95% CI 1.606-3.395,
      P = 0.000) and distant metastasis (pooled OR = 2.456, 95% CI 1.407-4.286, P =
      0.002). Moreover, MALAT1 was also related with tumour size (pooled OR = 1.875,
      95% CI 1.257-2.795, P = 0.002) and TNM stage (pooled OR = 2.034, 95% CI 1.111
      3.724, P = 0.021). Additionally, elevated MALAT1 expression could predict poor OS
      (pooled HR = 2.298, 95% CI 1.953-2.704, P = 0.000), DFS (pooled HR = 2.036, 95%
      CI 1.240-3.342, P = 0.005), RFS (pooled HR = 2.491, 95% CI 1.505-4.123, P =
      0.000), DSS (pooled HR = 2.098, 95% CI 1.372-3.211, P = 0.001) and PFS (pooled HR
      = 1.842, 95% CI 1.138-2.983, P = 0.013) in multivariate model. Importantly,
      subgroup analyses disclosed that increased MALAT1 expression had a poor OS among
      different cancer types (Estrogen-dependent cancer: pooled HR = 2.656, 95% CI
      1.560-4.523; urological cancer: pooled HR = 1.952, 95% CI 1.189-3.204; glioma:
      pooled HR = 2.315, 95% CI 1.643-3.263; digestive cancer: pooled HR = 2.451, 95%
      CI 1.862-3.227). Conclusions: The present findings demonstrated that MALAT1 may
      be a novel biomarker for predicting survival outcome, lymph node metastasis and
      distant metastasis.

PMID- 30093842
TI  - Don't Blame the System; They've Chosen the Wrong One.
AB  - While trying to represent patients in the design of integrated care, I have heard
      the words system, systemic and holism used frequently. Few of those using the
      words seem to be aware of the history of systems thinking, or its principles.
      Health interventions are instead designed using logic modelling, which is
      aholistic and disintegrative. This concern is illustrated in relation to the UK's
      Better Care Fund, which was an attempt to reduce hospital admissions by co
      ordinating care. Systems thinking is then used to provide a possible distinction
      between three operating systems for the UK's National Health Service (NHS). The
      first, an ideal market operating system, is inherently fantastic, and doubly so
      when it is impossible to determine who has contributed what to which outcomes.
      The accountable professional operating system may re-emerge as the rational
      option. However, weak analysis can lead to the emergence of a quasi-market
      operating system, which lacks the capacity to integrate the essential elements of
      a viable system. The fault lies not with systems thinking, but with the failure
      to study how viable systems are constructed.

PMID- 30093843
TI  - Policies Make Coherent Care Pathways a Personal Responsibility for Clinicians: A
      Discourse Analysis of Policy Documents about Coordinators in Hospitals.
AB  - Introduction: In response to increase of patients with complex conditions,
      policies prescribe measures for improving continuity of care. This study
      investigates policies introducing coordinator roles in Norwegian hospitals that
      have proven challenging to implement. Methods: This qualitative study of policy
      documents employed a discourse analysis inspired by Carol Bacchi's 'What's the
      problem represented to be?'. We analysed six legal documents (2011-2016) and
      selected parts of four whitepapers presenting the statutory patient care
      coordinator and contact physician roles in hospitals. Results: The 'problem'
      represented in the policies is lack of coherent pathways and lack of stable
      responsible professionals. Extended personal responsibility for clinical
      personnel as coordinators is the prescribed solution. Their duties are described
      in terms of ideals for coherent pathways across conditions and contexts. System
      measures to support and orchestrate the individual patient's pathway (e.g.
      resources, infrastructure) are scarcely addressed. Conclusions and Discussion: We
      suggest that the policies' construction of the 'problem' as a responsibility
      issue, result in that neither diversity of patients' coordination needs, nor
      heterogeneity of hospital contexts regarding necessary system support for
      coordinators, is set on the agenda. Adoption of rhetoric from diagnosis-specific
      standardized pathways obscures unique challenges in creating coherent pathways
      for patients with complex needs.

PMID- 30093841
TI  - Influence of Individual Radiosensitivity on the Adaptive Response Phenomenon:
      Toward a Mechanistic Explanation Based on the Nucleo-Shuttling of ATM Protein.
AB  - The adaptive response (AR) phenomenon generally describes a protective effect
      caused by a "priming" low dose (dAR) delivered after a period of time (DeltatAR)
      before a higher "challenging" dose (DAR). The AR is currently observed in human
      cells if dAR, DeltatAR, and DAR belong to (0.001-0.5 Gy), (2-24 hours), (0.1-5
      Gy), respectively. In order to investigate the molecular mechanisms specific to
      AR in human cells, we have systematically reviewed the experimental AR protocols,
      the cellular models, and the biological endpoints used from the 1980s. The AR
      appears to be preferentially observed in radiosensitive cells and is strongly
      dependent on individual radiosensitivity. To date, the model of the nucleo
      shuttling of the ATM protein provides a relevant mechanistic explanation of the
      AR molecular and cellular events. Indeed, the priming dose dAR may result in the
      diffusion of a significant amount of active ATM monomers in the nucleus. These
      ATM monomers, added to those induced directly by the challenging dose DAR, may
      increase the efficiency of the response to DAR by a better ATM-dependent DNA
      damage recognition. Such mechanistic model would also explain why AR is not
      observed in radioresistant or hyperradiosensitive cells. Further investigations
      at low dose are needed to consolidate our hypotheses.

PMID- 30093845
TI  - Understanding the Impact of Chronic Obstructive Pulmonary Disease and Intervening
      to Improve Self-Management in the Context of Multi-morbidity.

PMID- 30093844
TI  - Organizing Health Care Networks: Balancing Markets, Government and Civil Society.
AB  - Much is changing in health care organization today. A perspective or paradigm
      that is gaining ever increasing momentum is that of translational, extramural and
      integrated care. Current research suggests many potential benefits for integrated
      care and health care networks but the ethical issues are less frequently
      emphasized. Showing that integrated care can be beneficial, does not mean it is
      automatically ethically justified. We will argue for three ethical requirements
      such health care networks should meet. Subsequently we will look at the
      mechanisms driving the formation of networks and examine how these can cause
      networks to meet or fail to meet these ethical requirements or obligations. The
      three mechanisms we will examine are government, civil society and market
      mechanisms, which, we argue, should be balanced properly. Each mechanism is able
      to provide a relevant ethical perspective to health care networks. However, when
      the balance is skewed towards a single mechanism, health care networks might fail
      to promote one or more of the ethical requirements.

PMID- 30093846
TI  - Income Difference in Attitudes towards Cancer in General Population: Findings
      from a National Survey.
AB  - Background: To better understand cancer-related health behaviors, it is critical
      to know how general populations with different socioeconomic and demographic
      backgrounds perceive cancer. The current paper explored differences in general
      attitudes and beliefs towards cancer among Koreans. Methods: A cross-sectional
      national survey was conducted for 1,000 Korean participants who were not cancer
      patients and did not have immediate family members with cancer via proportional
      quota random sampling. General attitudes and beliefs about cancer were measured
      by face-to-face interview using the awareness and beliefs about cancer (ABC)
      measure. Results: Most respondents (84.8%-88.5%) had optimistic attitudes towards
      cancer. However, 35.6% to 87.7% agreed with negative cancer beliefs across all
      age groups simultaneously. Socioeconomic disparity of positive cancer beliefs was
      not evident. Unexpectedly, the highest income group agreed more strongly with the
      negatively framed statements that cancer treatment is worse than the cancer
      itself (odds ratio [OR], 2.68; 95% confidence interval [CI], 1.31-5.53), that
      they would not want to know if they have cancer (OR, 1.61; 95% CI, 0.94-2.75),
      and that a cancer diagnosis is a death sentence (OR, 2.32; 95% CI, 1.34-4.01),
      than the lowest income group. Conclusion: The present results imply a complicated
      context of cancer beliefs in Korea, unlike those shown in the studies of western
      populations. While the contradictory attitudes toward cancer can be attributable
      to the dual nature of information processing, social environment might have
      played a role. The association between socioeconomic status and negative
      attitudes toward cancer may vary depending on the diversity of the contexts.

PMID- 30093847
TI  - Oral Allergy Syndrome in Birch Pollen-Sensitized Patients from a Korean
      University Hospital.
AB  - Background: Oral allergy syndrome (OAS) is a type of allergic reaction that
      mainly occurs on oral contact with raw fruit, vegetables, or nuts. The most
      common type of OAS is birch pollen-related food allergy. Although OAS is a common
      food allergy in adults, only few epidemiologic studies have been reported in
      Korea. Here we investigate the prevalence and triggers of birch pollen-related
      food allergy. Methods: We conducted a retrospective chart review of 1,427
      patients who underwent a skin prick test for inhalant allergens at the Asthma and
      Allergy Clinic in Seoul National University Bundang Hospital from January 2011 to
      December 2016. Results: Of 1,427 patients, 125 (8.7%) were sensitized to birch
      pollen. Among them, 20.0% developed OAS, which was the most common food allergy
      (96.2%). The prevalence of OAS was higher in females, and was 18.2% in birch
      pollen-sensitized allergic rhinoconjunctivitis patients. Further, 72.0% OAS
      patients had rhinoconjunctivitis, 20.0% had asthma, and 12.0% had chronic
      urticaria. Apple (68.0%), peach (56.0%), nuts (36.0%), kiwi (20.0%), persimmon
      (20.0%), plum (16.0%), and cherry (16.0%) were frequent triggers; however,
      Chinese yam, kudzu vine, bellflower root, codonopsis, and ginseng were also
      revealed as triggers. Patients (60.0%) showed OAS with >= 3 foods at the same
      time. Only 3 patients showed mono-sensitivity to birch pollen, while others were
      multi-sensitized to trees, grasses, weed, or house dust mite allergens.
      Conclusion: OAS was the most common food allergy in birch pollen-sensitized
      patients. This study revealed the unique triggers of OAS in Korea in addition to
      well-known triggers.

PMID- 30093848
TI  - Marker Pen Device with Concentration Gradient Nib for Antibiotic Susceptibility
      Testing.
AB  - Background: Pen-based devices have emerged as useful tools for measuring pH and
      glucose, and for fabricating microchannels and microarrays. Pen-based devices
      take advantage of flexible patterning, inexpensive costs, and small volumes,
      thereby saving time and increasing efficiency. We have developed a gradient nib
      marker pen device that generated simultaneously different antibiotic
      concentrations in bacteria antibiotic susceptibility testing (AST). Methods: The
      device can deposit on the target surface with the antibiotic gradient. The
      designed polyester fiber nibs are a highly uniform porosity with unidirectional
      orientation and produce a visible gradient pattern. Results: We have demonstrated
      and quantitatively analyzed bacterial growth after antibiotic marking. The
      antibiotic marking produces an inhibition zone of bacterial growth. The
      inhibition zones of bacterial growth are captured and converted to 8-bit
      grayscale images, and then quantified by gray values using the Image J program. A
      profile of the inhibition zone showed different gray values in response to
      bacterial viability. Conclusion: The gradient nib marker pen device can be used
      to determine the quantitative antibiotic concentration based on the relationship
      between gray values and bacterial density conveniently without requiring a series
      of dilution tubes, including nutrient medium, and diversely diluted antibiotics.

PMID- 30093849
TI  - Erratum: Correction of Phrase: Risk Factors Associated with Estimated Glomerular
      Filtration Rate in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis
      after Treatment with Biological Disease Modifying Anti-Rheumatic Drugs.
AB  - [This corrects the article e214 in vol. 33, PMID: 30034307.].

PMID- 30093850
TI  - Comparison of ELISA and Urine Microscopy for Diagnosis of Schistosoma haematobium
      Infection.
AB  - Background: Schistosoma haematobium which causes urogenital schistosomiasis (UGS)
      is highly prevalent in African countries. Urine microscopy (UM) is the first-line
      diagnostic method of UGS. Enzyme-linked immunosorbent assay (ELISA) is a common
      method for screening many parasite infections primarily or alternatively. The
      present study established an in-house diagnostic system by ELISA and evaluated
      its diagnostic efficacy in comparison with UM for screening UGS in White Nile
      State, Republic of Sudan, 2011-2013. Methods: A total of 490 participants were
      screened by UM or ELISA, and 149 by both. The in-house ELISA system was
      established employing soluble egg antigen of S. haematobium and the cut-off
      absorbance was set at 0.270. Results: Of the 149 subjects, 58 participants
      (38.9%) were positive by UM, 119 (79.9%) were positive by ELISA and 82 (55.0%)
      showed consistently positive or negative results by both methods. The diagnostic
      sensitivity of ELISA was 94.8% and specificity was 29.7% based on UM results. The
      ELISA positive serum samples also cross-reacted with egg antigens of Schistosoma
      mansoni and Schistosoma japonicum. Conclusion: We have established in-house ELISA
      for screening serum immunoglobulin (Ig) G antibodies by employing soluble egg
      antigen of S. haematobium for diagnosis of UGS with 94.8% sensitivity and 29.7%
      specificity. The ELISA system can supplement the conventional diagnosis by UM.

PMID- 30093851
TI  - Palladium-Catalyzed Triarylation of sp3 C-H Bonds in Heteroarylmethanes:
      Synthesis of Triaryl(heteroaryl)methanes.
AB  - A straightforward method for the palladium-catalyzed triarylation of
      heteroarylmethanes at the methyl group has been developed. The reaction works
      with a variety of aryl halides, enabling the rapid synthesis of
      triaryl(heteroaryl)methanes in moderate to excellent yields.

PMID- 30093852
TI  - An in Vivo Mouse Model to Investigate the Effect of Local Anesthetic
      Nanomedicines on Axonal Conduction and Excitability.
AB  - Peripheral nerve blocks (PNBs) using local anesthetic (LA) are superior to
      systemic analgesia for management of post-operative pain. An insufficiently short
      PNB duration following single-shot LA can be optimized by development of extended
      release formulations among which liposomes have been shown to be the least toxic.
      In vivo rodent models for PNB have focused primarily on assessing behavioral
      responses following LA. In a previous study in human volunteers, we found that it
      is feasible to monitor the effect of LA in vivo by combining conventional
      conduction studies with nerve excitability studies. Here, we aimed to develop a
      mouse model where the same neurophysiological techniques can be used to
      investigate liposomal formulations of LA in vivo. To challenge the validity of
      the model, we tested the motor PNB following an unilamellar liposomal
      formulation, filled with the intermediate-duration LA lidocaine. Experiments were
      carried out in adult transgenic mice with fluorescent axons and with fluorescent
      tagged liposomes to allow in vivo imaging by probe-based confocal laser
      endomicroscopy. Recovery of conduction following LA injection at the ankle was
      monitored by stimulation of the tibial nerve fibers at the sciatic notch and
      recording of the plantar compound motor action potential (CMAP). We detected a
      delayed recovery in CMAP amplitude following liposomal lidocaine, without
      detrimental systemic effects. Furthermore, CMAP threshold-tracking studies of the
      distal tibial nerve showed that the increased rheobase was associated with a
      sequence of excitability changes similar to those found following non
      encapsulated lidocaine PNB in humans, further supporting the translational value
      of the model.

PMID- 30093854
TI  - Correction: Neurophysiological Basis of Multi-Scale Entropy of Brain Complexity
      and Its Relationship With Functional Connectivity.
AB  - [This corrects the article DOI: 10.3389/fnins.2018.00352.].

PMID- 30093855
TI  - Gender Differences in Processing Fearful and Angry Body Expressions.
AB  - Previous studies have demonstrated differential perception of body expressions
      between males and females. However, only two recent studies (Kret et al., 2011;
      Kruger et al., 2013) explored the interaction effect between observer gender and
      subject gender, and it remains unclear whether this interaction between the two
      gender factors is gender-congruent (i.e., better recognition of emotions
      expressed by subjects of the same gender) or gender-incongruent (i.e., better
      recognition of emotions expressed by subjects of the opposite gender). Here, we
      used event-related potentials (ERPs) to investigate the recognition of fearful
      and angry body expressions posed by males and females. Male and female observers
      also completed an affective rating task (including valence, intensity, and
      arousal ratings). Behavioral results showed that male observers reported higher
      arousal rating scores for angry body expressions posed by females than males. ERP
      data showed that when recognizing angry body expressions, female observers had
      larger P1 for male than female bodies, while male observers had larger P3 for
      female than male bodies. These results indicate gender-incongruent effects in
      early and later stages of body expression processing, which fits well with the
      evolutionary theory that females mainly play a role in care of offspring while
      males mainly play a role in family guarding and protection. Furthermore, it is
      found that in both angry and fearful conditions male observers exhibited a larger
      N170 for male than female bodies, and female observers showed a larger N170 for
      female than male bodies. This gender-incongruent effect in the structural
      encoding stage of processing may be due to the familiarity of the body configural
      features of the same gender. The current results provide insights into the
      significant role of gender in body expression processing, helping us understand
      the issue of gender vulnerability associated with psychiatric disorders
      characterized by deficits of body language reading.

PMID- 30093856
TI  - Inhibit My Disinhibition: The Role of the Inferior Frontal Cortex in Sexual
      Inhibition and the Modulatory Influence of Sexual Excitation Proneness.
AB  - Sexual behaviour is the result of an interplay between distinct neural inhibitory
      and excitatory mechanisms. Individual differences in sexual excitation and sexual
      inhibition are proposed to play an important role in the processes sustaining the
      regulation of sexual behaviour. While much research has focused on the neural
      correlates of response inhibition, highlighting a prominent role of the inferior
      frontal gyrus (IFG), very little is known regarding the neural mechanisms
      underlying different aspects of sexual inhibition. Here, we experimentally
      combined functional magnetic resonance imaging (fMRI) and transcranial magnetic
      stimulation (TMS) to: (i) test the functional role of IFG during motivational and
      cognitive sexual inhibition; and (ii) reveal whether this IFG involvement in
      sexual inhibitory processes depends on sexual excitation and sexual inhibition as
      traits. Twenty-two participants performed an Approach-Avoidance (AA) and a
      Negative Affective Priming (NAP) paradigm to assess motivational and cognitive
      sexual inhibition respectively. Our fMRI study showed IFG being selectively
      activated during cognitive but not motivational sexual inhibition. Importantly,
      the level of this neural activity was modulated by individual sexual excitation
      scores. Interestingly, a transient disruption of IFG activity using TMS led to an
      improvement in cognitive, not motivational, sexual inhibition, but only when
      accounting for individual sexual excitation scores. These findings clearly
      document that sexual excitation modulates IFG activity levels during cognitive
      sexual inhibition, and at the same time determines the effects of TMS on IFG by
      improving cognitive control exclusively for individuals with high sexual
      excitation scores. These findings provide new insights regarding the functional
      role of IFG, and underscore the relevance of individual psychological differences
      in understanding the brain mechanisms underlying socioaffective processes.

PMID- 30093857
TI  - Movement-Based Control for Upper-Limb Prosthetics: Is the Regression Technique
      the Key to a Robust and Accurate Control?
AB  - Due to the limitations of myoelectric control (such as dependence on muscular
      fatigue and on electrodes shift, difficulty in decoding complex patterns or in
      dealing with simultaneous movements), there is a renewal of interest in the
      movement-based control approaches for prosthetics. The latter use residual limb
      movements rather than muscular activity as command inputs, in order to develop
      more natural and intuitive control techniques. Among those, several research
      works rely on the interjoint coordinations that naturally exist in human upper
      limb movements. These relationships are modeled to control the distal joints
      (e.g., elbow) based on the motions of proximal ones (e.g., shoulder). The
      regression techniques, used to model the coordinations, are various [Artificial
      Neural Networks, Principal Components Analysis (PCA), etc.] and yet, analysis of
      their performance and impact on the prosthesis control is missing in the
      literature. Is there one technique really more efficient than the others to model
      interjoint coordinations? To answer this question, we conducted an experimental
      campaign to compare the performance of three common regression techniques in the
      control of the elbow joint on a transhumeral prosthesis. Ten non-disabled
      subjects performed a reaching task, while wearing an elbow prosthesis which was
      driven by several interjoint coordination models obtained through different
      regression techniques. The models of the shoulder-elbow kinematic relationship
      were built from the recordings of fifteen different non-disabled subjects that
      performed a similar reaching task with their healthy arm. Among Radial Basis
      Function Networks (RBFN), Locally Weighted Regression (LWR), and PCA, RBFN was
      found to be the most robust, based on the analysis of several criteria including
      the quality of generated movements but also the compensatory strategies exhibited
      by users. Yet, RBFN does not significantly outperform LWR and PCA. The regression
      technique seems not to be the most significant factor for improvement of
      interjoint coordinations-based control. By characterizing the impact of the
      modeling techniques through closed-loop experiments with human users instead of
      purely offline simulations, this work could also help in improving movement-based
      control approaches and in bringing them closer to a real use by patients.

PMID- 30093858
TI  - BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines.
AB  - Beta-site amyloid-precursor-protein cleaving enzyme 1 (BACE1) is the rate
      limiting protease in the production of the amyloid-beta peptide (Abeta), which is
      considered to be the causative agent in the pathogenesis of Alzheimer's Disease
      (AD). Therefore, the therapeutic potential of pharmacological BACE1 inhibitors is
      currently tested in clinical trials for AD treatment. To ensure a positive
      clinical outcome it is crucial to identify and evaluate adverse effects
      associated with BACE1 inhibition. Preclinical studies show that chronic blockade
      of BACE1 activity alters synaptic functions and leads to loss of dendritic
      spines. To assess the mechanism of synapse loss, dendritic spine dynamics of
      pyramidal layer V cells were monitored by in vivo two-photon microscopy in the
      somatosensory cortex of mice, treated with the BACE1 inhibitor MK-8931. MK-8931
      treatment significantly reduced levels of Abeta40 and density of dendritic spines
      in the brain. However, the steady decline in dendritic spine density specifically
      resulted from a diminished formation of new spines and not from a loss of stable
      spines. Furthermore, the described effects on spine formation were transient and
      recovered after inhibitor withdrawal. Since MK-8931 inhibition did not completely
      abolish spine formation, our findings suggest that carefully dosed inhibitors
      might be therapeutically effective without affecting the structural integrity of
      excitatory synapses if given at an early disease stage.

PMID- 30093853
TI  - Immune and Neuroprotective Effects of Physical Activity on the Brain in
      Depression.
AB  - Physical activity-a lifestyle factor that is associated with immune function,
      neuroprotection, and energy metabolism-modulates the cellular and molecular
      processes in the brain that are vital for emotional and cognitive health,
      collective mechanisms that can go awry in depression. Physical activity optimizes
      the stress response, neurotransmitter level and function (e.g., serotonergic,
      noradrenergic, dopaminergic, and glutamatergic), myokine production (e.g.,
      interleukin-6), transcription factor levels and correlates [e.g., peroxisome
      proliferator-activated receptor C coactivator-1alpha [PGC-1alpha], mitochondrial
      density, nitric oxide pathway activity, Ca2+ signaling, reactive oxygen specie
      production, and AMP-activated protein kinase [AMPK] activity], kynurenine
      metabolites, glucose regulation, astrocytic health, and growth factors (e.g.,
      brain-derived neurotrophic factor). Dysregulation of these interrelated processes
      can effectuate depression, a chronic mental illness that affects millions of
      individuals worldwide. Although the biogenic amine model has provided some
      clinical utility in understanding chronic depression, a need remains to better
      understand the interrelated mechanisms that contribute to immune dysfunction and
      the means by which various therapeutics mitigate them. Fortunately, convergent
      evidence suggests that physical activity improves emotional and cognitive
      function in persons with depression, particularly in those with comorbid
      inflammation. Accordingly, the aims of this review are to (1) underscore the link
      between inflammatory correlates and depression, (2) explicate immuno
      neuroendocrine foundations, (3) elucidate evidence of neurotransmitter and
      cytokine crosstalk in depressive pathobiology, (4) determine the immunomodulatory
      effects of physical activity in depression, (5) examine protocols used to
      effectuate the positive effects of physical activity in depression, and (6)
      highlight implications for clinicians and scientists. It is our contention that a
      deeper understanding of the mechanisms by which inflammation contributes to the
      pathobiology of depression will translate to novel and more effective treatments,
      particularly by identifying relevant patient populations that can benefit from
      immune-based therapies within the context of personalized medicine.

PMID- 30093859
TI  - A Scoping Review of the Quality and the Design of Evaluations of Mobile Health,
      Telehealth, Smart Pump and Monitoring Technologies Performed in a Pharmacy
      Related Setting.
AB  - Background: There is currently a need for high quality evaluations of new mobile
      health, telehealth, smart pump and monitoring technologies undertaken in a
      pharmacy-related setting. We aim to evaluate the use of these monitoring
      technologies performed in this setting. Methods: A systematic searching of
      English articles that examined the quality and the design of technologies
      conducted in pharmacy-related facilities was performed using the following
      databases: MEDLINE and Cumulative index to Nursing and Allied Health Literature
      (CINAHL) to identify original studies examining the quality and the design of
      technologies and published in peer-reviewed journals. Extraction of articles and
      quality assessment of included articles were performed independently by two
      authors. Quality scores over 75% are classed as being acceptable using a
      "relatively conservative" quality benchmark. Scores over 55% are included using a
      "relatively liberal" cut-off point. Results: Screening resulted in the selection
      of 40 formal evaluations. A substantial number of studies (32, 80.00%) were
      performed in the United States, quantitative in approach (33, 82.50%) and
      retrospective cohort (24, 60.00%) in study design. The most common pharmacy
      related settings were: 22 primary care (55.00%); 10 hospital pharmacy (25.00%); 7
      community pharmacy (17.50%); one primary care and hospital pharmacy (2.50%). The
      majority of the evaluations (33, 82.50%) reported clinical outcomes, six (15.00%)
      measured clinical and economic outcomes, and one (2.50%) economic only. Twelve
      (30.00%) quantitative studies and no qualitative study met objective criteria for
      "relatively conservative" quality. Using a lower "relatively liberal" benchmark,
      27 quantitative (81.82%) and four qualitative (57.41%) studies met the lower
      quality criterion. Conclusion: Worldwide, few evaluations of mobile health,
      telehealth, smart pump and monitoring technologies in pharmacy-related setting
      have been published.Their quality is often below the standard necessary for
      inclusion in a systematic review mainly due to inadequate study design.

PMID- 30093860
TI  - Optimal Regimens and Cutoff Evaluation of Tildipirosin Against Pasteurella
      multocida.
AB  - Pasteurella multocida (PM) can invade the upper respiratory tract of the body and
      cause death and high morbidity. Tildipirosin, a new 16-membered-ring macrolide
      antimicrobial, has been recommended for the treatment of respiratory diseases.
      The objective of this research was to improve the dose regimes of tildipirosin to
      PM for reducing the macrolides resistance development with the
      pharmacokinetic/pharmacodynamic (PK/PD) modeling approach and to establish an
      alternate cutoff for tildipirosin against PM. A single dose (4 mg/kg body weight)
      of tildipirosin was administered via intramuscular (i.m.) and intravenous (i.v.)
      injection to the pigs. The minimum inhibitory concentration (MIC) values of
      clinical isolates (112) were measured in the range of 0.0625-32 MUg/ml, and the
      MIC50 and MIC90 values were 0.5 and 2 MUg/ml, respectively. The MIC of the
      selected PM04 was 2 and 0.5 MUg/ml in the tryptic soy broth (TSB) and serum,
      respectively. The main pharmacokinetic (PK) parameters including the area under
      the curve at 24 h (AUC24 h), AUC, terminal half-life (T1/2), the time to peak
      concentration (Tmax), peak concentration (Cmax), relative total systemic
      clearance (CLb), and the last mean residence time (MRTlast) were calculated to be
      7.10, 7.94 MUg*h/ml, 24.02, NA h, NA MUg/ml, 0.46 L/h*kg, 8.06 h and 3.94, 6.79
      MUg*h/ml, 44.04, 0.25 h, 0.98 MUg/ml, 0.43 L/h*kg, 22.85 h after i.v. and i.m.
      induction, respectively. Moreover, the bioavailability of i.m. route was 85.5%,
      and the unbinding of tildipirosin to serum protein was 78%. The parameters AUC24
      h/MIC in serum for bacteriostatic, bactericidal, and elimination activities were
      calculated as 18.91, 29.13, and 34.03 h based on the inhibitory sigmoid Emax
      modeling. According to the Monte Carlo simulation, the optimum doses for
      bacteriostatic, bactericidal, and elimination activities were 6.10, 9.41, and
      10.96 mg/kg for 50% target and 7.86, 12.17, and 14.57 mg/kg for 90% target,
      respectively. The epidemiological cutoff value (ECV) was calculated to be 4
      MUg/ml which could cover 95% wild-type clinical isolates distribution. The PK-PD
      cutoff (COPD) was analyzed to be 0.25 MUg/ml in vitro for tildipirosin against PM
      based on the Monte Carlo simulation. Compared with these two cutoff values, the
      finial susceptible breakpoint was defined as 4 MUg/ml. The data presented now
      provides the optimal regimens (12.17 mg/kg) and susceptible breakpoint (4 MUg/ml)
      for clinical use, but these predicted data should be validated in the clinical
      practice.

PMID- 30093861
TI  - Enhancement of Tumor Cell Death by Combining gef Gene Mediated Therapy and New
      1,4-Benzoxazepin-2,6-Dichloropurine Derivatives in Breast Cancer Cells.
AB  - New treatment modalities are urgently needed to better manage advanced breast
      cancer. Combination therapies are usually more effective than monotherapy. In
      this context, the use of cyclic and acyclic O,N-acetals derivative compounds in
      combination with the suicide gef gene shown a potent anti-tumor activity and
      represent a new generation of anticancer agents. Here, we evaluate the use of the
      gef gene to promote and increase the anti-tumor effect of cyclic and acyclic O,N
      acetals purine derivatives and elucidate their mechanisms of action. Among all
      compounds tested, those with a nitro group and a cyclic pattern structures (FC
      30b2, FC-29c, and bozepinib) are the most benefited from the gef gene effect.
      These compounds, in combination with gef gene, were able to abolish tumor cell
      proliferation with a minimal dose leading to more effective and less toxic
      chemotherapy. The effect of this combined therapy is triggered by apoptosis
      induction which can be found deregulated in the later stage of breast cancer.
      Moreover, the combined therapy leads to an increase of cell post-apoptotic
      secondary necrosis that is able to promote the immunogenicity of cancer cells
      leading to a successful treatment. This data suggests that this novel combination
      therapy represents a promising candidate for breast cancer treatment.

PMID- 30093862
TI  - Anti-endometriosis Mechanism of Jiawei Foshou San Based on Network Pharmacology.
AB  - Jiawei Foshou San (JFS) is the new formula originated from classic Foshou San
      formula, composed with ligustrazine, ferulic acid, and tetrahydropalmatine.
      Previously JFS inhibited the growth of endometriosis (EMS) with unclear
      mechanism, especially in metastasis, invasion, and epithelial-mesenchymal
      transition. In this study, network pharmacology was performed to explore
      potential mechanism of JFS on EMS. Through compound-compound target and compound
      target-EMS target networks, key targets were analyzed for pathway enrichment. MMP
      TIMP were uncovered as one cluster of the core targets. Furthermore, autologous
      transplantation of EMS rat's model were used to evaluate in vivo effect of JFS on
      invasion, metastasis and epithelial-mesenchymal transition. JFS significantly
      suppressed the growth, and reduced the volume of ectopic endometrium, with
      modification of pathologic structure. In-depth study, invasion and metastasis
      were restrained after treating with JFS through decreasing MMP-2 and MMP-9,
      increasing TIMP-1. Meanwhile, JFS promoted E-cadherin, and attenuated N-cadherin,
      Vimentin, Snail, Slug, ZEB1, ZEB2, Twist. In brief, anti-EMS effect of JFS might
      be related to the regulation of epithelial-mesenchymal transformation, thereby
      inhibition of invasion and metastasis. These findings reveal the potential
      mechanism of JFS on EMS and the benefit for further evaluation.

PMID- 30093863
TI  - Triptolide Induces Apoptosis Through Fas Death and Mitochondrial Pathways in
      HepaRG Cell Line.
AB  - Triptolide isolated from the traditional Chinese herb Tripterygium wilfordii Hook
      F., possesses anti-tumor, anti-fertility, and anti-inflammatory properties.
      Triptolide-induced hepatotoxicity has continued to engage the attention of
      researchers. However, not much is yet known about the cytotoxicity of triptolide,
      and the precise mechanisms involved. In the present study, we investigated the
      cytotoxicity of triptolide and its underlying mechanisms, using the in vitro
      model (HepaRG cell). The results demonstrated that triptolide significantly
      reduced cell viability and induced apoptosis in HepaRG cells in a dose- and time
      dependent manner. Triptolide treatment also provoked reactive oxygen species
      (ROS) generation and depolarization of mitochondrial membrane potential (MMP).
      Moreover, triptolide dose-dependently increased the protein expression levels of
      Fas, Bax, p53, p21, cyclin E, cleaved caspase-3, 8, and 9; and subsequent
      cleavage of poly (ADP-ribose) polymerase (PARP). However, the protein expression
      of Bcl-2, cyclin A, and CDK 2 were significantly decreased. These results suggest
      that triptolide inhibits cell proliferation and induces apoptosis via the Fas
      death pathway and the mitochondrial pathway.

PMID- 30093864
TI  - Danhong Injection Enhances the Therapeutic Efficacy of Mesenchymal Stem Cells in
      Myocardial Infarction by Promoting Angiogenesis.
AB  - Stem cell-based therapies have the potential to dramatically transform the
      treatment and prognosis of myocardial infarction (MI), and mesenchymal stem cells
      (MSCs) have been suggested as a promising cell population to ameliorate the heart
      remodeling in post-MI. However, poor implantation and survival in ischemic
      myocardium restrict its efficacy and application. In this study, we sought to use
      the unique mode of action of Chinese medicine to improve this situation.
      Surrounding the myocardial infarct area, we performed a multi-point MSC
      transplantation and administered in conjunction with Danhong injection, which is
      mainly used for the treatment of MI. Our results showed that the MSC survival
      rate and cardiac function were improved significantly through the small animal
      imaging system and echocardiography, respectively. Moreover, histological
      analysis showed that MSC combined with DHI intervention significantly reduced
      myocardial infarct size in myocardial infarcted mice and significantly increased
      MSC resident. To investigate the mechanism of DHI promoting MSC survival and cell
      migration, PCR and WB experiments were performed. Our results showed that DHI
      could promote the expression of CXC chemokine receptor 4 in MSC and enhance the
      expression of stromal cell-derived factor-1 in myocardium, and this effect can be
      inhibited by AMD3100 (an SDF1/CXCR4 antagonist). Additionally, MSC in combination
      with DHI interfered with MI in mice and this signifies that when combined, the
      duo could the expression of vascular endothelial growth factor (VEGF) in the
      marginal zone of infarction compared with when either MSC or DHI are used
      individually. Based on these results, we conclude that DHI enhances the residence
      of MSCs in cardiac tissue by modulating the SDF1/CXCR4 signaling pathway. These
      findings have important therapeutic implications for Chinese medicine-assisted
      cell-based therapy strategies.

PMID- 30093866
TI  - One-Year Consumption of a Mediterranean-Like Dietary Pattern With Vitamin D3
      Supplements Induced Small Scale but Extensive Changes of Immune Cell Phenotype,
      Co-receptor Expression and Innate Immune Responses in Healthy Elderly Subjects:
      Results From the United Kingdom Arm of the NU-AGE Trial.
AB  - Amongst the major features of aging are chronic low grade inflammation and a
      decline in immune function. The Mediterranean diet (MedDiet) is considered to be
      a valuable tool to improve health status, and although beneficial effects have
      been reported, to date, immunological outcomes have not been extensively studied.
      We aimed to test the hypothesis that 1 year of a tailored intervention based on
      the MedDiet with vitamin D (10 MUg/day) would improve innate immune responses in
      healthy elderly subjects (65-79 years) from the English cohort (272 subjects
      recruited) of the NU-AGE randomized, controlled study (clinicaltrials.gov,
      NCT01754012). Of the 272 subjects forming the United Kingdom cohort a subgroup of
      122 subjects (61 in the intervention group and 61 in the control group) was used
      to evaluate ex vivo innate immune response, phenotype of circulating immune
      cells, and levels of pro- and anti-inflammatory markers. Odds Ratio (OR) was
      calculated for all the parameters analyzed. After adjustment by gender, MedDiet
      females with a BMI < 31 kg/m2 had a significant upregulation of circulating
      CD40+CD86+ cells (OR 3.44, 95% CI 1.01-11.75, P = 0.0437). Furthermore, in all
      MedDiet subjects, regardless of gender, we observed a MedDiet-dependent changes,
      although not statistically significant of immune-critical parameters including T
      cell degranulation, cytokine production and co-receptor expression. Overall, our
      study showed that adherence to an individually tailored Mediterranean-like
      dietary pattern with a daily low dose of vitamin D3 supplements for 1 year
      modified a large variety of parameters of immune function in healthy, elderly
      subjects. We interpreted these data as showing that the MedDiet in later life
      could improve aspects of innate immunity and thus it could aid the design of
      strategies to counteract age-associated disturbances. Clinical Trial
      Registration: clinicaltrials.gov, NCT01754012.

PMID- 30093865
TI  - Comprehensive Transcriptome Analysis Reveals Competing Endogenous RNA Networks
      During Avian Leukosis Virus, Subgroup J-Induced Tumorigenesis in Chickens.
AB  - Avian leukosis virus subgroup J (ALV-J) is an avian oncogenic retrovirus that
      induces myeloid tumors and hemangiomas in chickens and causes severe economic
      losses with commercial layer chickens and meat-type chickens. High-throughput
      sequencing followed by quantitative real-time polymerase chain reaction and
      bioinformatics analyses were performed to advance the understanding of regulatory
      networks associated with differentially expressed non-coding RNAs and mRNAs that
      facilitate ALV-J infection. We examined the expression of mRNAs, long non-coding
      RNAs (lncRNAs), and miRNAs in the spleens of 20-week-old chickens infected with
      ALV-J and uninfected chickens. We found that 1723 mRNAs, 7,883 lncRNAs and 13
      miRNAs in the spleen were differentially expressed between the uninfected and
      infected groups (P < 0.05). Transcriptome analysis showed that, compared to mRNA,
      chicken lncRNAs shared relatively fewer exon numbers and shorter transcripts.
      Through competing endogenous RNA and co-expression network analyses, we
      identified several tumor-associated or immune-related genes and lncRNAs. Along
      transcripts whose expression levels significantly decreased in both ALV-J
      infected spleen and tumor tissues, BCL11B showed the greatest change. These
      results suggest that BCL11B may be mechanistically involved in tumorigenesis in
      chicken and neoplastic diseases, may be related to immune response, and
      potentially be novel biomarker for ALV-J infection. Our results provide new
      insight into the pathology of ALV-J infection and high-quality transcriptome
      resource for in-depth study of epigenetic influences on disease resistance and
      immune system.

PMID- 30093867
TI  - Autophagy Dysfunction and Oxidative Stress, Two Related Mechanisms Implicated in
      Retinitis Pigmentosa.
AB  - Retinitis pigmentosa (RP) is one of the most common clinical subtypes of retinal
      degeneration (RD), and it is a neurodegenerative disease that could cause
      complete blindness in humans because it ultimately affects the photoreceptors
      viability. RP afflicts an estimated 1.5 million patients worldwide. The retina is
      highly susceptible to oxidative stress which can impair mitochondrial function.
      Many retina pathologies, such as diabetic retinopathy and secondary cone
      photoreceptor death in RP, have been related directly or indirectly with
      mitochondrial dysfunction. The possible role of autophagy in retina and cell
      differentiation is described and also the implications of autophagy dysregulation
      in RP. The present review shows the crucial role of autophagy in maintaining the
      retina homeostasis and possible therapeutic approaches for the treatment of RP.

PMID- 30093871
TI  - Expectations in the Ultimatum Game: Distinct Effects of Mean and Variance of
      Expected Offers.
AB  - Being treated fairly by others is an important need in everyday life.
      Experimentally, fairness can be studied using the Ultimatum Game, where the
      decision to reject a low, but non-zero offer is seen as a way to punish the other
      player for an unacceptable offer. The canonical explanation of such behavior is
      inequity aversion: people prefer equal outcomes over personal gains. However,
      there is abundant evidence that people's decision to reject a low offer can be
      changed by contextual factors and their emotional state, which cannot be
      explained by the inequity aversion model. Here, we expand a recent alternative
      explanation: rejections are driven by deviations from expectations: the larger
      the difference between the actual offer and the expected offer, the more likely
      one is to reject the offer. Specifically, we provided participants with explicit
      information on what kind of offers to expect using histograms depicting
      distribution of offers given in a previous experiment by the same proposers.
      Crucially, we showed four different distributions, manipulating both the mean and
      the variance of these expected sets of offers. We found that 50% of our
      participants clearly and systematically changed their behavior as a function of
      their expectations (11% followed the standard-economic model of pure self
      interest and 39% where not distinguishable from the inequity-aversion model).
      Using a logistic mixed-model analysis, we found that the mean and variance
      differently affect the decision to reject an offer. Specifically, the mean
      expected offer affected the threshold of what offers are acceptable, while the
      expected variance of offers changed how strict participants were about this
      threshold. Together, these results suggest that social expectations have a more
      complex nature as current theories propose.

PMID- 30093872
TI  - Language Dominance Affects Bilingual Performance and Processing Outcomes in
      Adulthood.
AB  - This study examines the role of language dominance (LD) on linguistic competence
      outcomes in two types of early bilinguals: (i) child L2 learners of Catalan (L1
      Spanish-L2 Catalan and, (ii) child Spanish L2 learners (L1 Catalan-L2 Spanish).
      Most child L2 studies typically focus on the development of the languages during
      childhood and either focus on L1 development or L2 development. Typically, these
      child L2 learners are immersed in the second language. We capitalize on the
      unique situation in Catalonia, testing the Spanish and Catalan of both sets of
      bilinguals, where dominance in either Spanish or Catalan is possible. We examine
      the co-occurrence of Sentential Negation (SN) with a Negative Concord Item (NCI)
      in pre-verbal position (Catalan only) and Differential Object Marking (DOM)
      (Spanish only). The results show that remaining dominant in the L1 contributes to
      the maintenance of target-like behavior in the language.

PMID- 30093873
TI  - Recycling Alone or Protesting Together? Values as a Basis for Pro-environmental
      Social Change Actions.
AB  - Social change can be pursued by participating in a public protest, joining a
      community gardening initiative, or recycling at home. However, little research
      has investigated how individual differences in values relate to people's
      engagement in different types of social change actions in the context of pro
      environmental behavior. We hypothesized that values would be differentially
      related to different types of social change actions, based on different goals
      that each of these actions may have (e.g., changing one's own behavior or
      influencing others). A survey among people engaged in pro-environmental activism
      during the 2015 United Nations Climate Change Conference supported our
      predictions. Specifically, we found that individual behavior and community-based
      actions were uniquely related to biospheric values (i.e., a key concern for
      nature and the environment). However, other social change actions (e.g., public
      protest) were uniquely related to altruistic values (i.e., a key concern for the
      welfare of all people), and pro-environmental lobbying was positively related to
      egoistic values (i.e., a key concern for power and achievement). Our findings
      suggest that different behaviors directed at pro-environmental social change may
      be based on different values. We discuss the theoretical and practical
      implications of these findings.

PMID- 30093870
TI  - Neural and Behavioral Predictors of Treatment Efficacy on Mood Symptoms and
      Cognition in Mood Disorders: A Systematic Review.
AB  - Background: The clinical and etiological heterogeneity of mood disorders impede
      identification of effective treatments for the individual patient. This
      highlights a need for early neuronal and behavioral biomarkers for treatment
      efficacy, which can provide a basis for more personalized treatments. The present
      systematic review aimed to identify the most consistent neuronal and behavioral
      predictors of treatment efficacy on mood symptoms and cognitive impairment in
      mood disorders. Methods: We identified and included 60 original peer-reviewed
      studies investigating neuroimaging and behavioral predictors of treatment
      efficacy within the domains of emotional and non-emotional cognition, structural
      neuroimaging, and resting state functional connectivity in patients with unipolar
      or bipolar disorder. Results: Lower baseline responsivity in limbic regions
      coupled with heightened medial and dorsal prefrontal responses to emotional
      stimuli were the most consistent predictors of response to pharmacotherapy for
      depression. In contrast, heightened limbic and ventral prefrontal reactivity to
      emotional stimuli seemed to predict efficacy of psychological interventions.
      Early modulation of fronto-limbic activity and reduction in negative bias were
      also associated with treatment response. Better performance on non-emotional
      tests at baseline was relatively consistently associated with efficacy on mood
      symptoms, whereas the association between neural activity during non-emotional
      tests and treatment response was less clear. Other baseline factors associated
      with treatment response were greater white matter integrity, resting state
      functional connectivity, more prefrontal gray matter volume as well as an early
      increase following short administered treatment. Finally, emerging evidence
      indicates that baseline cognitive deficits are associated with greater chances of
      achieving treatment efficacy on cognition. Conclusions: Patients' profile of
      emotional and non-emotional cognition and neural activity-and the early treatment
      associated changes in neural and cognitive function-may be useful for guiding
      treatments for depression. While cognitive deficits at baseline seem to improve
      chances of treatment efficacy on cognition, more studies of this association are
      urgently needed.

PMID- 30093868
TI  - Inositol 1,4,5-Trisphosphate Receptors in Hypertension.
AB  - Chronic hypertension remains a major cause of global mortality and morbidity. It
      is a complex disease that is the clinical manifestation of multiple genetic,
      environmental, nutritional, hormonal, and aging-related disorders. Evidence
      supports a role for vascular aging in the development of hypertension involving
      an impairment in endothelial function together with an alteration in vascular
      smooth muscle cells (VSMCs) calcium homeostasis leading to increased myogenic
      tone. Changes in free intracellular calcium levels ([Ca2+] i ) are mediated
      either by the influx of Ca2+ from the extracellular space or release of Ca2+ from
      intracellular stores, mainly the sarcoplasmic reticulum (SR). The influx of
      extracellular Ca2+ occurs primarily through voltage-gated Ca2+ channels (VGCCs),
      store-operated Ca2+ channels (SOC), and Ca2+ release-activated channels (CRAC),
      whereas SR-Ca2+ release occurs through inositol trisphosphate receptor (IP3R) and
      ryanodine receptors (RyRs). IP3R-mediated SR-Ca2+ release, in the form of Ca2+
      waves, not only contributes to VSMC contraction and regulates VGCC function but
      is also intimately involved in structural remodeling of resistance arteries in
      hypertension. This involves a phenotypic switch of VSMCs as well as an alteration
      of cytoplasmic Ca2+ signaling machinery, a phenomena tightly related to the aging
      process. Several lines of evidence implicate changes in expression/function
      levels of IP3R isoforms in the development of hypertension, VSMC phenotypic
      switch, and vascular aging. The present review discusses the current knowledge of
      these mechanisms in an integrative approach and further suggests potential new
      targets for hypertension management and treatment.

PMID- 30093874
TI  - A Role Theory Perspective on How and When Goal-Focused Leadership Influences
      Employee Voice Behavior.
AB  - Despite an increasing number of studies that identify leaders' role in promoting
      employees' voice behavior, little is known about the role that supervisors' goal
      focused leadership plays in this. The current study aims to address this research
      gap by using the role theory to explain how supervisors' goal-focused leadership
      influences employees' voice behavior and the conditions under which supervisors'
      have maximum impact on employee voice. A field study of 197 employees and their
      immediate supervisors offered support for our model. The results indicated a
      positive association between goal-focused leadership and employees' voice
      behavior that was mediated by leaders' omission of reward and punishments. We
      also found that perceived helping and support from coworkers positively moderated
      the relationship between leaders' reward and punishment omission and employees'
      voice behavior such that the relationship was weaker when coworker helping and
      support was higher. The findings provide more comprehensive picture of the
      process by which goal-focused leadership influences employee voice and highlight
      how coworkers can buffer the negative effect of ineffective managerial reward and
      punishment omission. The practical implications of this research, its limitations
      and directions for future research are also discussed.

PMID- 30093869
TI  - Biological Predictors of Clozapine Response: A Systematic Review.
AB  - Background: Clozapine is the recommended antipsychotic for treatment-resistant
      schizophrenia (TRS) but there is significant variability between patients in the
      degree to which clozapine will improve symptoms. The biological basis of this
      variability is unknown. Although clozapine has efficacy in TRS, it can elicit
      adverse effects and initiation is often delayed. Identification of predictive
      biomarkers of clozapine response may aid initiation of clozapine treatment, as
      well as understanding of its mechanism of action. In this article we
      systematically review prospective or genetic studies of biological predictors of
      response to clozapine. Methods: We searched the PubMed database until 20th
      January 2018 for studies investigating "clozapine" AND ("response" OR "outcome")
      AND "schizophrenia." Inclusion required that studies examined a biological
      variable in relation to symptomatic response to clozapine. For all studies except
      genetic-studies, inclusion required that biological variables were measured
      before clozapine initiation. Results: Ninety-eight studies met the eligibility
      criteria and were included in the review, including neuroimaging, blood-based,
      cerebrospinal fluid (CSF)-based, and genetic predictors. The majority (70) are
      genetic studies, collectively investigating 379 different gene variants, however
      only three genetic variants (DRD3 Ser9Gly, HTR2A His452Tyr, and C825T GNB3) have
      independently replicated significant findings. Of the non-genetic variables, the
      most consistent predictors of a good response to clozapine are higher prefrontal
      cortical structural integrity and activity, and a lower ratio of the dopamine and
      serotonin metabolites, homovanillic acid (HVA): 5-hydroxyindoleacetic acid (5
      HIAA) in CSF. Conclusions: Recommendations include that future studies should
      ensure adequate clozapine trial length and clozapine plasma concentrations, and
      may include multivariate models to increase predictive accuracy.

PMID- 30093875
TI  - Measuring Intimate Partner Violence and Traumatic Affect: Development of VITA, an
      Italian Scale.
AB  - In a global context where the percentage of women who are victim of violence is
      still high (World Health Organization, 2013), intimate partner violence (IPV) can
      be considered the most widespread form of violence against women: in such cases
      violent attacks are perpetuated or threatened by a partner or ex-partner within
      an intimate relationship, which makes its recognition more difficult. IPV
      requires specific tools and, although the literature has highlighted the specific
      role played by some emotions (such as shame, guilt, and fear) that keep women
      experiencing this violence in a state of passivity and confusion, to date too
      little attention has been given to the construction of sound instruments able to
      detect post-traumatic affectivity. Such instruments could facilitate women who
      have suffered from IPV in recognizing it and in making the responses of women's
      health services more sensitive and structured. This study illustrates a
      sequential item development process to elaborate a new self-report instrument
      (VITA Scale: Intimate Violence and Traumatic Affects Scale) for assessing the
      intensity of post-traumatic affect derived from IPV. Within a psychodynamic
      perspective, the scale is characterized by four affects: fear, as a state of
      alarm elicited by the avoidance of the danger; terror, as a paralyzing state that
      hinders an active process of reaction; shame as a strong exposure to the other
      that disarms the individual and the guilt as a defensive dimension aiming at the
      restoring of the link with the abusive partner. Trough specific methodological
      steps, a 28-item set was selected and administered to a sample of 302 Italian
      women who declared themselves as having suffered from IPV. Explorative and
      confirmatory factor analysis, as well as correlations with well-established
      concurrent tools were computed in order to investigate its psychometric property.
      A factorial structure composed of four factors, consistent with theoretical
      scales and a good internal consistency (Cronbach's alphas from 0.80 to 0.90)
      emerged. The VITA Scale could be a useful tool for clinicians and researchers to
      investigate the intensity of the affective state of the woman suffered from IPV.
      It could be useful to better address the clinical practice and therapeutic
      intervention planning.

PMID- 30093876
TI  - Generalized Trust and Financial Risk-Taking in China - A Contextual and
      Individual Analysis.
AB  - Previous evidence from developed nations has suggested that more trusting
      individuals are more likely to take financial risks, such as investing in the
      stock market. Previous studies have found that Chinese citizens have particularly
      high generalized trust and are more risk-seeking in investment compared with
      Americans, which makes China an interesting case. The current study examines the
      relation between generalized trust and stock market participation in China at
      both a contextual and individual level. Across provinces, a lower level of
      generalized trust was associated with stock market participation. For example,
      the stock market participation was four times higher in provinces with the lowest
      level of perceived fairness than in provinces with the highest level of perceived
      fairness. The contextual effects of less generalized trust suggest an association
      between risk-taking behaviors and societal level inequality. At the individual
      level, trust of strangers was associated with risk preference in highly educated
      and wealthy people but its effect on risk behaviors was not clear. The findings
      suggest that trust may affect financial risk-taking behavior at different levels
      through different pathways, and that cultural differences in understanding of
      trust also need to be considered.

PMID- 30093879
TI  - Structural Brain Network Alteration and its Correlation With Structural
      Impairments in Patients With Depression in de novo and Drug-Naive Parkinson's
      Disease.
AB  - Purpose: Depression is common in Parkinson's disease (PD) and is correlated with
      the severity of motor deficits and quality of life. The present study aimed to
      investigate alterations in the structural brain network related to depression in
      Parkinson's disease (d-PD) and their correlations with structural impairments of
      white matter (WM). Materials and Methods: Data were acquired from the Parkinson
      Progression Markers Initiative (PPMI) database. A total of 84 de novo and drug
      naive PD patients were screened and classified into two groups according to the
      15-item Geriatric Depression Scale (GDS-15): d-PD (n = 28) and nondepression in
      PD (nd-PD, n = 56). Additionally, 37 healthy controls (HC) were screened. All
      subjects underwent DTI and 3D-T1WI on a 3.0 T MR scanner. Individual structural
      brain networks were constructed and analyses were performed using graph theory
      and network-based statistics (NBS) at both global and local levels. Differences
      in global topological properties were explored among the three groups. The
      association models between node and edge changes and the GDS-15 were constructed
      to detect regions that were specifically correlated with d-PD. Tract-based
      spatial statistics (TBSS) was used to detect structural impairments of WM between
      the d-PD and nd-PD groups. The correlations between altered global topological
      properties and structural impairments were analyzed in the d-PD group. Results:
      The global efficiency and characteristic path length of the structural brain
      network were impaired in the d-PD group compared with those in the nd-PD and HC
      groups. Thirteen nodes and 1 subnetwork with 10 nodes and 12 edges specifically
      correlated with d-PD were detected. The left hippocampus, left parahippocampal,
      left lingual, left middle occipital, left inferior occipital, left fusiform, left
      middle temporal, and left inferior temporal regions were all involved in the
      results of node and edge analysis. No WM microstructural impairments were
      identified in the d-PD group. Conclusion: Our study suggests that the integration
      of the structural brain network is impaired with disrupted connectivity of limbic
      system and visual system in the de novo and drug-naive d-PD patients.The
      topological properties assessing integration of the structural brain network can
      serve as a potential objective neuroimaging marker for early diagnosis of d-PD.

PMID- 30093878
TI  - Primary cCT Imaging Based Clinico-Neurological Assessment-Calling for Addition of
      Telestroke Video Consultation in Patients With Intracerebral Hemorrhage.
AB  - Background and Purpose: Intracerebral hemorrhage (ICH) requires rapid decision
      making to decrease morbidity and mortality although time frame and optimal
      therapy are still ill defined. Ideally, specialized neurologists, neurosurgeons,
      and (neuro-) radiologists who know the patient's clinical status and their
      cerebral computed tomography imaging (cCT) make a joint decision on the clinical
      management. However, in telestroke networks, a shift toward cCT imaging criteria
      used for decision making can be observed for practical reasons. Here we
      investigated the "reverse correlation" from cCT imaging to the actual clinical
      presentation as evaluated by the Glasgow Coma Scale (GCS) and the National
      Institutes of Health Stroke Scale (NIHSS). Methods: CCT images and basic
      information (age, sex, and time of onset) of 50 patients with hypertensive and
      lobar ICH were presented to 14 experienced neurologists and 15 neurosurgeons.
      Based on this information, the NIHSS and GCS scores were estimated for each
      patient. The differences between the actual GCS and NIHSS scores and the cCT
      imaging-based estimated scores were plotted in a bland-Altman plot. Results: The
      average estimated GCS score mainly based on cCT imaging was 12. 4 +/- 2.8 (actual
      value: 13.0 +/- 2.5; p = 0.100), the estimated NIHSS score was 13.9 +/- 9.1
      (actual value: 10.8 +/- 7.3; p < 0.001). Thus, in cCT-imaging-based evaluation,
      the neurological status of patients especially employing the NIHSS was estimated
      poorer, particularly in patients with lobar ICH. "Reverse clinical" evaluation
      based on cCT-imaging alone may increase the rate of intubation and secondary
      transferal and neurosurgical treatment. Telestroke networks should consider both,
      videoassessment of the actual clinical picture and cCT-imaging findings to make
      appropriate acute treatment decisions.

PMID- 30093877
TI  - Disruption of Inferior Longitudinal Fasciculus Microstructure in Parkinson's
      Disease: A Systematic Review of Diffusion Tensor Imaging Studies.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder accompanied by a series
      of pathological mechanisms which contribute to a variety of motor and non-motor
      symptoms. Recently, there has been an increasing interest in structural diffusion
      tensor imaging (DTI) in PD which has shed light on our understanding of
      structural abnormalities underlying PD symptoms or its associations with
      pathological mechanisms. One of the white matter tracts shown to be disrupted in
      PD with a possible contribution to some PD symptoms is the inferior longitudinal
      fasciculus (ILF). On the whole, lower ILF integrity contributes to thought
      disorders, impaired visual emotions, cognitive impairments such as semantic
      fluency deficits, and mood disorders. This review outlines the microstructural
      changes in ILF associated with systemic inflammation and various PD symptoms like
      cognitive decline, facial emotion recognition deficit, depression, color
      discrimination deficit, olfactory dysfunction, and tremor genesis. However, few
      studies have investigated DTI correlates of each symptom and larger studies with
      standardized imaging protocols are required to extend these preliminary findings
      and lead to more promising results.

PMID- 30093881
TI  - Corpus Callosum Radiomics-Based Classification Model in Alzheimer's Disease: A
      Case-Control Study.
AB  - Background: Alzheimer's disease (AD) is a progressive neurodegenerative disease
      that causes the decline of some cognitive impairments. The present study aimed to
      identify the corpus callosum (CC) radiomic features related to the diagnosis of
      AD and build and evaluate a classification model. Methods: Radiomics analysis was
      applied to the three-dimensional T1-weighted magnetization-prepared rapid
      gradient echo (MPRAGE) images of 78 patients with AD and 44 healthy controls
      (HC). The CC, in each subject, was segmented manually and 385 features were
      obtained after calculation. Then, the feature selection were carried out. The
      logistic regression model was constructed and evaluated according to identified
      features. Thus, the model can be used for distinguishing the AD from HC subjects.
      Results: Eleven features were selected from the three-dimensional T1-weighted
      MPRAGE images using the LASSO model, following which, the logistic regression
      model was constructed. The area under the receiver operating characteristic curve
      values (AUC), sensitivity, specificity, accuracy, precision, and positive and
      negative predictive values were 0.720, 0.792, 0.500, 0.684, 0.731, 0.731, and
      0.583, respectively. Conclusion: The results demonstrated the potential of CC
      texture features as a biomarker for the diagnosis of AD. This is the first study
      showing that the radiomics model based on machine learning was a valuable method
      for the diagnosis of AD.

PMID- 30093880
TI  - Association of Visual Tracking Metrics With Post-concussion Symptomatology.
AB  - Attention impairment may provide a cohesive neurobiological explanation for
      clusters of clinical symptoms that occur after a concussion; therefore, objective
      quantification of attention is needed. Visually tracking a moving target is an
      attention-dependent sensorimotor function, and eye movement can be recorded
      easily and objectively to quantify performance. Our previous work suggested the
      utility of gaze-target synchronization metrics of a predictive visual tracking
      task in concussion screening and recovery monitoring. Another objectively
      quantifiable performance measure frequently suggested for concussion screening is
      simple visuo-manual reaction time (simple reaction time, SRT). Here, we used
      visual tracking and SRT tasks to assess changes between pre- and within-2-week
      post-concussion performances and explore their relationships to post-concussion
      symptomatology. Athletes participating in organized competitive sports were
      recruited. Visual tracking and SRT records were collected from the recruited
      athlete pool as baseline measures over a 4-year period. When athletes experienced
      a concussion, they were re-assessed within 2 weeks of their injury. We present
      the data from a total of 29 concussed athletes. Post-concussion symptom burden
      was assessed with the Rivermead Post-Concussion Symptoms Questionnaire and
      subscales of the Brain Injury Screening Questionnaire. Post-concussion changes in
      visual tracking and SRT performance were examined using a paired t-test.
      Correlations of changes in visual tracking and SRT performance to symptom burden
      were examined using Pearson's coefficients. Post-concussion changes in visual
      tracking performance were not consistent among the athletes. However, changes in
      several visual tracking metrics had moderate to strong correlations to symptom
      scales (r up to 0.68). On the other hand, while post-concussion SRT performance
      was reduced (p < 0.01), the changes in the performance metrics were not
      meaningfully correlated to symptomatology (r <= 0.33). Results suggest that
      visual tracking performance metrics reflect clinical symptoms when assessed
      within 2 weeks of concussion. Evaluation of concussion requires assessments in
      multiple domains because the clinical profiles are heterogeneous. While most
      individuals show recovery within a week of injury, others experience prolonged
      recovery periods. Visual tracking performance metrics may serve as a biomarker of
      debilitating symptoms of concussion implicating attention as a root cause of such
      pathologies.

PMID- 30093882
TI  - Up-To-Date Review About Minipuberty and Overview on Hypothalamic-Pituitary
      Gonadal Axis Activation in Fetal and Neonatal Life.
AB  - Minipuberty consists of activation of the hypothalamic-pituitary-gonadal (HPG)
      axis during the neonatal period, resulting in high gonadotropin and sex steroid
      levels, and occurs mainly in the first 3-6 months of life in both sexes. The rise
      in the levels of these hormones allows for the maturation of the sexual organs.
      In boys, the peak testosterone level is associated with penile and testicular
      growth and the proliferation of gonadic cells. In girls, the oestradiol levels
      stimulate breast tissue, but exhibit considerable fluctuations that probably
      reflect the cycles of maturation and atrophy of the ovarian follicles.
      Minipuberty allows for the development of the genital organs and creates the
      basis for future fertility, but further studies are necessary to understand its
      exact role, especially in girls. Nevertheless, no scientific study has yet
      elucidated how the HPG axis turns itself off and remains dormant until puberty.
      Additional future studies may identify clinical implications of minipuberty in
      selected cohorts of patients, such as premature and small for gestational age
      infants. Finally, minipuberty provides a fundamental 6-month window of the
      possibility of making early diagnoses in patients with suspected sexual
      reproductive disorders to enable the prompt initiation of treatment rather than
      delaying treatment until pubertal failure.

PMID- 30093883
TI  - The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous
      Activity.
AB  - The EMPA-REG OUTCOME study revealed that a sodium-glucose cotransporter 2 (SGLT2)
      inhibitor, empagliflozin, can remarkably reduce cardiovascular (CV) mortality and
      heart failure in patients with high-risk type 2 diabetes. Recently, the CANVAS
      program also showed that canagliflozin, another SGLT2 inhibitor, induces a lower
      risk of CV events. However, the precise mechanism by which an SGLT2 inhibitor
      elicits CV protective effects is still unclear. Possible sympathoinhibitory
      effects of SGLT2 inhibitor have been suggested, as significant blood pressure
      (BP) reduction, following treatment with an SGLT2 inhibitor, did not induce
      compensatory changes in heart rate (HR). We have begun to characterize the
      effects of SGLT2 inhibitor on BP and sympathetic nervous activity (SNA) in salt
      treated obese and metabolic syndrome rats, who develop hypertension with an
      abnormal circadian rhythm of BP, a non-dipper type of hypertension, and do not
      exhibit a circadian rhythm of SNA. Treatment with SGLT2 inhibitors significantly
      decreased BP and normalized circadian rhythms of both BP and SNA, but did not
      change HR; this treatment was also associated with an increase in urinary sodium
      excretion. Taken together, these data suggest that an SGLT2 inhibitor decreases
      BP by normalizing the circadian rhythms of BP and SNA, which may be the source of
      its beneficial effects on CV outcome in high-risk patients with type 2 diabetes.
      In this review, we briefly summarize the effects of SGLT2 inhibitors on BP and
      HR, with a special emphasis on SNA.

PMID- 30093884
TI  - Molecular Mechanisms of Syndromic Cryptorchidism: Data Synthesis of 50 Studies
      and Visualization of Gene-Disease Network.
AB  - Background: Cryptorchidism is one of the most frequent congenital birth defects
      in male children and is present in 2-4% of full-term male births. It has several
      possible health effects including reduced fertility, increased risk for
      testicular neoplasia, testicular torsion, and psychological consequences.
      Cryptorchidism is often diagnosed as comorbid; copresent with other diseases. It
      is also present in clinical picture of several syndromes. However, this field has
      not been systematically studied. The aim of the present study was to catalog
      published cases of syndromes which include cryptorchidism in the clinical picture
      and associated genomic information. Methods: The literature was extracted from
      Public/Publisher MEDLINE and Web of Science databases, using the keywords
      including: syndrome, cryptorchidism, undescended testes, loci, and gene. The
      obtained data was organized in a table according to the previously proposed
      standardized data format. The results of the study were visually represented
      using Gephi and karyotype view. Results: Fifty publications had sufficient data
      for analysis. Literature analysis resulted in 60 genomic loci, associated with 44
      syndromes that have cryptorchidism in clinical picture. Genomic loci included 38
      protein-coding genes and 22 structural variations containing microdeletions and
      microduplications. Loci, associated with syndromic cryptorchidism are located on
      16 chromosomes. Visualization of retrieved data is presented in a gene-disease
      network. Conclusions: The study is ongoing and further studies will be needed to
      develop a complete catalog with the data from upcoming publications. Additional
      studies will also be needed for revealing of molecular mechanisms associated with
      syndromic cryptorchidism and revealing complete diseasome network.

PMID- 30093885
TI  - Improved Cardiovascular and Cardiometabolic Risk in Patients With Type 1 Diabetes
      and Autoimmune Polyglandular Syndrome Switched From Glargine to Degludec Due to
      Hypoglycaemic Variability.
AB  - Background: Cardiovascular disease is a frequent complication of type 1 diabetes
      (T1D). We evaluated the effectiveness of switching from glargine to degludec in
      reducing the cardiovascular risk factors, the Framingham risk score (FRS) and
      visceral adiposity index (VAI) in patients with T1D and autoimmune polyglandular
      syndrome (APS). Methods: We selected 66 T1D outpatients who had been on stable
      treatment with glargine for at least 5 years. Among them, 30 patients maintained
      glargine (group A), while 36 were switched to degludec (group B) for 12 months.
      At baseline and after 12 months of observation, clinical and metabolic
      parameters, insulin dose, 30-days blood glucose (BG) self monitoring, VAI and FRS
      were obtained. Results: At baseline, patients in group B had more hypoglycaemic
      episodes and prevalence of hypertension than those in group A. After 12 months on
      degludec, patients in group B had a significant decrease in BMI (p = 0.003),
      waist circumference (p < 0.001), total daily insulin as U/day and U/kg (p = 0.001
      for both), basal insulin as U/day and U/kg (p = 0.001 for both), HbA1c (p <
      0.001), mean (p = 0.035) and standard deviation of daily BG (p = 0.017), mean pre
      meal BG (p = 0.016), number of hypoglycaemic episodes (p = 0.001), VAI (p =
      0.012) and FRS (p = 0.019) and a significant increase in HDL-C (p < 0.001),
      compared to baseline. At 12 months of treatment a significant decrease in BMI (p
      = 0.017), WC (p = 0.003), SBP (p = 0.001), DBP (p = 0.005), basal insulin as
      U/day (p = 0.018) and U/kg (p = 0.045), HbA1c (p = 0.040) and FRS (p = 0.010) was
      observed in group B compared to group A. Conclusions: Our preliminary data
      suggest that 12 months' treatment with degludec is associated with an improvement
      of glycaemic control, cardiometabolic and cardiovascular risk, compared to
      glargine, in patients with T1D and APS.

PMID- 30093887
TI  - A Comprehensive Research on Antibiotic Resistance Genes in Microbiota of Aquatic
      Animals.
AB  - The occurrence of antibiotic resistance genes (ARGs) as emerging contaminants is
      of continued concern for human health. Antibiotics used in aquaculture have
      promoted the evolution and spread of ARGs. This study aimed to investigate the
      occurrence of 37 ARGs conferring resistance to six classes of antibiotics in 94
      aquatic animals from five cities in southeast coast of China. The results showed
      that floR, sulII, sulI, strB, strA, aadA, and tetS were identified as the
      prominent ARGs with the high detection frequencies ranging from 30.9 to 51.1% in
      total samples. Then relative expression amount of seven prominent ARGs quantified
      by qPCR, ranging from 0.003 to 0.065. The tetS was the most abundant ARG among
      the seven ARGs. Though aadA was the second highest detection frequency of ARGs,
      it was the lowest expression amount ARG. The occurrences and abundances of ARGs
      in freshwater aquatic animals were greater than those in marine, reflecting the
      discrepancy of cultivation pattern between the freshwater and marine aquaculture.
      Shanghai was considered as the most prevalent site with 16 ARGs, and Ningbo
      merely contained 9 ARGs without of beta-lactam ARGs and quinolone ARGs, showing
      variations of ARGs with geographical location. Eight kinds of sulfonamides and
      one chloramphenicol residues were further measured in samples from Shanghai.
      Interestingly, no target antibiotics were found, but sulfonamides resistance
      genes (sulI, sulII) and chloramphenicol resistance genes (floR) persisted at
      aquatic animals in the absence of selection pressure. Our research firstly shows
      comprehensive information on the ARGs in skin microbiota of aquatic animals,
      which could provide useful information and a new insight for better understanding
      on the ARGs dissemination in aquatic animals.

PMID- 30093886
TI  - Study the Features of 57 Confirmed CRISPR Loci in 38 Strains of Staphylococcus
      aureus.
AB  - Staphylococcus aureus is a foodborne pathogen that causes food contamination and
      food poisoning, which poses great harm to health, agriculture and other hosts.
      Clustered regularly interspaced short palindromic repeats (CRISPR) are a recently
      discovered bacterial immune system that resists foreign genes such as phage DNA.
      This system inhibits the transfer of specific movable genetic elements that match
      the CRISPR spacer sequences, thereby preventing the spread of drug-resistant
      genes between pathogens. In this study, 57 CRISPR loci were screened from 38
      strains of S. aureus based on the CRISPR database, and bioinformatics tools were
      used to investigate the structural features and potential functions of S. aureus
      CRISPR loci. The results showed that most strains contained only one CRISPR
      locus, a few strains contained multiple loci with sparsely distributed sites.
      These loci mainly included highly conserved direct repeat sequences and highly
      variable spacer sequences, as well as polymorphic cas genes. In addition, the
      analysis of secondary structure of direct repeat RNA showed that all sites can
      form stable RNA secondary structure. The results of constructing phylogenetic
      tree based on spacer sequence showed that some strains contained a high degree of
      phylogenetic relationship, while the differences among other strains in
      evolutionary processes were quite obvious. Of the 57 CRISPR loci identified, only
      the cas gene was found near the 4 CRISPR loci.

PMID- 30093888
TI  - Tucuma Oil Shifted Ruminal Fermentation, Reducing Methane Production and Altering
      the Microbiome but Decreased Substrate Digestibility Within a RUSITEC Fed a Mixed
      Hay - Concentrate Diet.
AB  - Tucuma oil is sourced from the fruit pulp of the tucuma tree and contains high
      concentrations of unsaturated fatty acids and carotenoids. Due to these
      properties it may have the potential to decrease enteric methane (CH4) from
      ruminants when included in the diet. The objective of this study was to determine
      the effect of oil mechanically extracted from the fruit pulp of tucuma on
      fermentation characteristics, CH4 production and the microbial community using
      the rumen stimulation technique. Treatments consisted of a control diet
      (forage:concentrate; 70:30), and tucuma oil included at 0.5 or 1.0% (v/v).
      Addition of tucuma oil linearly decreased (P < 0.01) dry matter disappearance.
      Total gas (mL/d) and carbon dioxide (CO2) production (mL/d, mL/g DM) were
      unaffected (P >= 0.36) to increasing addition of tucuma oil where 0.5% (v/v) of
      Tucuma oil numerically increased both variables. Acetate and butyrate percentages
      of total VFA were linearly decreased (P <= 0.01) and propionate and valerate
      percentages of total VFA were linearly increased (P < 0.01) by increasing
      concentrations of tucuma oil added to the substrate. The ratio of acetate to
      propionate was linearly decreased (P < 0.01) with increasing concentration of
      tucuma oil. Methane production (mL/d) was linearly decreased (P = 0.04) with
      increasing addition of tucuma oil to the substrate. Tucuma oil reduced the
      bacterial richness and diversity when included at 1.0% (v/v) in both solid- and
      liquid- associated microbes. The abundance of the genera Fibrobacter and
      Rikenellaceae RC9 gut group were decreased and Pyramidobacter, Megasphaera,
      Anaerovibrio, and Selenomonas were enriched by the addition of 1.0% tucuma oil.
      In conclusion, tucuma oil resulted in the favorable shift in fermentation
      products away from acetate toward propionate, decreasing the production of CH4
      when tucuma oil was included at 1.0% (v/v), however, substrate digestibility was
      also inhibited. The rumen microbiota was also altered by the addition of tucuma
      oil.

PMID- 30093889
TI  - Heterologous Expression of Biopreservative Bacteriocins With a View to Low Cost
      Production.
AB  - Bacteriocins, a heterogenous group of antibacterial ribosomally synthesized
      peptides, have potential as bio-preservatives in in a wide range of foods and as
      future therapeutics for the inhibition of antibiotic-resistant bacteria. While
      many bacteriocins have been characterized, several factors limit their production
      in large quantities, a requirement to make them commercially viable for food or
      pharma applications. The identification of new bacteriocins by database mining
      has been promising, but their potential is difficult to evaluate in the absence
      of suitable expression systems. E. coli has been used as a heterologous host to
      produce recombinant proteins for decades and has an extensive set of expression
      vectors and strains available. Here, we review the different expression systems
      for bacteriocin production using this host and identify the most important
      features to guarantee successful production of a range of bacteriocins.

PMID- 30093890
TI  - Low Affinity DnaA-ATP Recognition Sites in E. coli oriC Make Non-equivalent and
      Growth Rate-Dependent Contributions to the Regulated Timing of Chromosome
      Replication.
AB  - Although the mechanisms that precisely time initiation of chromosome replication
      in bacteria remain unclear, most clock models are based on accumulation of the
      active initiator protein, DnaA-ATP. During each cell division cycle, sufficient
      DnaA-ATP must become available to interact with a distinct set of low affinity
      recognition sites in the unique chromosomal replication origin, oriC, and
      assemble the pre-replicative complex (orisome) that unwinds origin DNA and helps
      load the replicative helicase. The low affinity oriC-DnaA-ATP interactions are
      required for the orisome's mechanical functions, and may also play a role in
      timing of new rounds of DNA synthesis. To further examine this possibility, we
      constructed chromosomal oriCs with equal preference for DnaA-ADP or DnaA-ATP at
      one or more low affinity recognition sites, thereby lowering the DnaA-ATP
      requirement for orisome assembly, and measured the effect of the mutations on
      cell cycle timing of DNA synthesis. Under slow growth conditions, mutation of any
      one of the six low affinity DnaA-ATP sites in chromosomal oriC resulted in
      initiation earlier in the cell cycle, but the shift was not equivalent for every
      recognition site. Mutation of tau2 caused a greater change in initiation age,
      suggesting its occupation by DnaA-ATP is a temporal bottleneck during orisome
      assembly. In contrast, during rapid growth, all origins with a single mutated
      site displayed wild-type initiation timing. Based on these observations, we
      propose that E. coli uses two different, DnaA-ATP-dependent initiation timing
      mechanisms; a slow growth timer that is directly coupled to individual site
      occupation, and a fast growth timer comprising DnaA-ATP and additional factors
      that regulate DnaA access to oriC. Analysis of origins with paired mutated sites
      suggests that Fis is an important component of the fast growth timing mechanism.

PMID- 30093891
TI  - High-Throughput Analysis Reveals Seasonal Variation of the Gut Microbiota
      Composition Within Forest Musk Deer (Moschus berezovskii).
AB  - The gut microbiota plays a key role in the nutritional ecology of ruminants, and
      host diet has a significant effect on these microbial communities. Longitudinal
      studies assessing variation of seasonal microbiota in animals can provide a
      comparative context for interpreting the adaptive significance of such changes.
      However, few studies have investigated the effects of seasonally-related dietary
      shifts on the gut microbial communities of endangered forest musk deer (FMD), and
      the national breeding programs need this information to promote the growth of
      captive populations. The present study applied bacterial 16S rRNA genes based on
      high-throughput sequencing to profile the fecal microbial communities of FMD
      across four seasons. Microbial diversity was higher in seasons with dry leaf
      diets (winter and spring) compared to seasons with fresh leaf diets (summer and
      autumn). The dominant microbial phyla were Firmicutes and Bacteroidetes, and the
      core bacterial taxa also comprised mostly (94.40% of shared OTUs) Firmicutes (37
      taxa) and Bacteroidetes (6 taxa), which were relatively stable across different
      seasons. The Firmicutes-Bacteroidetes ratio declined in seasons with fresh leaf
      diets relative to seasons with dry leaf diets, and the dominant genera among the
      four seasons showed no significant variation in abundance. This work explores the
      seasonal variation in the microbial communities of FMD for the first time, and
      reveals how gut microbial community dynamics vary seasonally in accordance with
      differences in dietary plants (fresh and dry leaf). These results indicate that
      the annual cyclic reconfiguration of FMD gut microbiota could be associated with
      shifts in dietary nutrients, which is important information to inform captive FMD
      management.

PMID- 30093892
TI  - Identification of a Torque Teno Mini Virus (TTMV) in Hodgkin's Lymphoma Patients.
AB  - At least 12% of human cancers are caused by virus infection. To understand
      whether other viruses are associated with human cancers, a viral metagenomics
      approach was used to analyze the composition of the viral communities of the
      serum of the patients with Hodgkin's lymphoma (HL) and non-Hodgkin lymphoma. In
      this report, a human anellovirus TTMV named TTMV-SH was discovered from three
      patients with HL. The complete genome of TTMV-SH is 2812nt in length.
      Phylogenetic analysis based on ORF1 indicated that TTMV-SH of the 11 isolates
      cluster with TTMV strain TLMV-CBD231 sharing only 60.3-62% sequence similarity,
      and the sequences divergence is 41.5-43.1%, which indicates that TTMV-SH is a
      novel species. The TTMV-SH prevalence in HL group, especially in nodular
      sclerosing Hodgkin's lymphomas (NSHL), was significantly higher than in the
      healthy group implicated that the TTMV-SH may be associated with HL, especially
      NSHL.

PMID- 30093893
TI  - Negative Binomial Mixed Models for Analyzing Longitudinal Microbiome Data.
AB  - The metagenomics sequencing data provide valuable resources for investigating the
      associations between the microbiome and host environmental/clinical factors and
      the dynamic changes of microbial abundance over time. The distinct properties of
      microbiome measurements include varied total sequence reads across samples, over
      dispersion and zero-inflation. Additionally, microbiome studies usually collect
      samples longitudinally, which introduces time-dependent and correlation
      structures among the samples and thus further complicates the analysis and
      interpretation of microbiome count data. In this article, we propose negative
      binomial mixed models (NBMMs) for longitudinal microbiome studies. The proposed
      NBMMs can efficiently handle over-dispersion and varying total reads, and can
      account for the dynamic trend and correlation among longitudinal samples. We
      develop an efficient and stable algorithm to fit the NBMMs. We evaluate and
      demonstrate the NBMMs method via extensive simulation studies and application to
      a longitudinal microbiome data. The results show that the proposed method has
      desirable properties and outperform the previously used methods in terms of
      flexible framework for modeling correlation structures and detecting dynamic
      effects. We have developed an R package NBZIMM to implement the proposed method,
      which is freely available from the public GitHub repository
      http://github.com//nyiuab//NBZIMM and provides a useful tool for analyzing
      longitudinal microbiome data.

PMID- 30093894
TI  - Heterologous Biosynthesis, Modifications and Structural Characterization of
      Ruminococcin-A, a Lanthipeptide From the Gut Bacterium Ruminococcus gnavus E1, in
      Escherichia coli.
AB  - Ruminococcin A (RumA) is a lanthipeptide with high activity against pathogenic
      clostridia and is naturally produced by the strict anaerobic bacterium
      Ruminococcus gnavus E1, isolated from human intestine. Cultivating R. gnavus E1
      is challenging, limiting high-quality production, further biotechnological
      development and therapeutic exploitation of RumA. To supply an alternative
      production system, the gene encoding RumA-modifying enzyme (RumM) and the gene
      encoding the unmodified precursor peptide (preRumA) were amplified from the
      chromosome of R. gnavus E1 and coexpressed in Escherichia coli. Our results show
      that the ruminococcin-A lanthionine synthetase RumM catalyzed dehydration of
      threonine and serine residues and subsequently installed thioether bridges into
      the core structure of a mutant version of preRumA (preRumA*). These modifications
      were achieved when the peptide was expressed as a fusion protein together with
      green fluorescence protein (GFP), demonstrating that a larger attachment to the N
      terminus of the leader peptide does not obstruct in vivo processivity of RumM in
      modifying the core peptide. The leader peptide serves as a docking sequence which
      the modifying enzyme recognizes and interacts with, enabling its catalytic role.
      We further investigated RumM catalysis in conjunction with the formation of
      complexes observed between RumM and the chimeric GFP fusion protein. Results
      obtained suggested some insights into the catalytic mechanisms of class II
      lanthipeptide synthetases. Our data further indicated the presence of three
      thioether bridges, contradicting a previous report whose findings ruled out the
      possibility of forming a third ring in RumA. Modified preRumA* was activated in
      vitro by removing the leader peptide using trypsin and biological activity was
      achieved against Bacillus subtilis ATCC 6633. A production yield of 6 mg of pure
      modified preRumA* per liter of E. coli culture was attained and considering the
      size ratio of the leader-to-core segments of preRumA*, this amount would generate
      a final yield of approximately 1-2 mg of active RumA when the leader peptide is
      removed. The yield of our system exceeds that attainable in the natural producer
      by several 1000-fold. The system developed herein supplies useful tools for
      product optimization and for performing in vivo peptide engineering to generate
      new analogs with superior anti-infective properties.

PMID- 30093895
TI  - Spatial Patterns and Drivers of Microbial Taxa in a Karst Broadleaf Forest.
AB  - Spatial patterns and drivers of soil microbial communities have not yet been well
      documented. Here, we used geostatistical modeling and Illumina sequencing of 16S
      rRNA genes to explore how the main microbial taxa at the phyla level are
      spatially distributed in a 25-ha karst broadleaf forest in southwest China.
      Proteobacteria, dominated by Alpha- and Deltaproteobacteria, was the most
      abundant phylum (34.51%) in the karst forest soils. Other dominating phyla were
      Actinobacteria (30.73%), and Acidobacteria (12.24%). Soil microbial taxa showed
      spatial dependence with an autocorrelation range of 44.4-883.0 m, most of them
      within the scope of the study plots (500 m). An increasing trend was observed for
      Alphaproteobacteria, Deltaproteobacteria, and Chloroflexi from north to south in
      the study area, but an opposite trend for Actinobacteria, Acidobacteira, and
      Firmicutes was observed. Thaumarchaeota, Bacteroidetes, Gemmatimonadetes, and
      Verrucomicrobia had patchy patterns, Nitrospirae had a unimodal pattern, and
      Latescibacteria had an intermittent pattern with low and high value strips.
      Location, soil total phosphorus, elevation, and plant density were significantly
      correlated with main soil bacterial taxa in the karst forest. Moreover, the total
      variation in soil microbial communities better explained by spatial factors than
      environmental variables. Furthermore, a large part of variation (76.8%) was
      unexplained in the study. Therefore, our results suggested that dispersal
      limitation was the primary driver of spatial pattern of soil microbial taxa in
      broadleaved forest in karst areas, and other environmental variables (i.e., soil
      porosity and temperature) should be taken into consideration.

PMID- 30093897
TI  - Non-toxigenic Clostridioides (Formerly Clostridium) difficile for Prevention of
      C. difficile Infection: From Bench to Bedside Back to Bench and Back to Bedside.
AB  - The beneficial effect of colonization of the gastrointestinal tract by non
      toxigenic Clostridioides difficile (NTCD) strains as a preventive of toxigenic C.
      difficile infection (CDI) has been known since the early 1980s. Investigators in
      both the USA and United Kingdom demonstrated that prior colonization by randomly
      selected NTCD strains provided prevention against infection by toxigenic C.
      difficile in hamsters, albeit with limited durability. In the 1980s two patients
      with multiply recurrent CDI in the UK were treated with vancomycin followed by
      NTCD to prevent further recurrences, with one success and one failure.
      Epidemiologic studies of hospitalized patients using weekly rectal swab cultures
      demonstrated that asymptomatic colonization of patients by toxigenic C. difficile
      was much more common than CDI, but also that the rate of asymptomatic NTCD
      colonization of patients was unexpectedly high. Development of molecular strain
      typing of C. difficile was instrumental in characterizing different strains of
      both toxigenic C. difficile and NTCD leading to identification of NTCD strains
      that were effective human colonizers. These strains were reintroduced in hamsters
      in the 1990s and shown to prevent CDI efficiently and durably when challenged
      with epidemic toxigenic C. difficile strains. One strain of NTCD, NTCD-M3, was
      manufactured under cGMP standards and was demonstrated to be safe in a phase 1
      volunteer trial. NTCD-M3 was then tested in a phase 2 double-blind placebo
      controlled trial for the prevention of recurrent CDI in patients experiencing
      their first CDI episode or first CDI recurrence. NTCD-M3 was given at doses of
      104 or 107 spores per day orally for 7 or 14 days following successful treatment
      of CDI with vancomycin and/or metronidazole. CDI recurred in 30% of placebo
      patients and 11% of all NTCD-M3 patients (p = 0.006); recurrence rate for the
      best dose, 107 spores/d * 7 days, was 5% (p = 0.01 vs. placebo). Detection of
      colonization predicted prevention success; among the 86 patients who were
      colonized with NTCD-M3 the recurrence rate was 2% vs. 31% in patients who
      received NTCD-M3 but were not colonized (p < 0.001). Additional trials of NTCD-M3
      for primary prevention of CDI and prevention of CDI recurrence seem warranted by
      these promising results.

PMID- 30093896
TI  - Traits-Based Integration of Multi-Species Inoculants Facilitates Shifts of
      Indigenous Soil Bacterial Community.
AB  - Microbial co-inoculation is considered to be an innovative approach and had been
      applied worldwide. However, the underlying mechanisms of microbial co-inoculants
      constructions, especially the trait-based combination of distinctly different
      microbial species remains poorly understood. In this study, we constructed two
      microbial co-inoculants with the same three strains with emphasis on the
      microbial, soil and plant traits. Microbial co-inoculants 1 (M1) were constructed
      according to soil fertility, microbial activity and cucumber nutrient requirement
      with a 2:1:2 ratio (Ensifer sp. NYM3, Acinetobacter sp. P16 and Flavobacterium
      sp. KYM3), while microbial co-inoculants 2 (M2) were constructed according to
      soil fertility and cucumber nutrient requirement with a 1:10:1 ratio without
      considering the difference in the nutrient supply capability of microbial
      species. The results showed that M1 and M2 both obviously increased cucumber
      yields. The M1 had significant highest pH value, total nitrogen (TN) and
      invertase activity (IA). The M2 had significant highest available phosphate (AP),
      NO3-N, urea activity (UA), and alkaline phosphatase activity (APA).
      Gammaproteobacteria, Acidobacteria, Nitrospirae, and Armatimonadetes were
      significantly increased, while Actinobacteria and Firmicutes were significantly
      decreased by microbial co-inoculations (M1 and M2). The bacterial lineages
      enriched in M1 were Gammaproteobacteria and TM7. Acidobacteria, Bacteroidetes,
      and Deltaproteobacteria were enriched in M2. Principal coordinate analysis (PCoA)
      analysis showed that the bacterial communities were strongly separated by the
      different microbial inoculation treatments. The functional groups of
      intracellular_parasites were highest in M1. The functional groups of phototrophy,
      photoautotrophy, nitrification, fermentation, cyanobacteria,
      oxygenic_photoautotrophy, chitinolysis and animal_parasites_or_symbionts were
      highest in M2. Based on correlation analysis, it inferred that the M1 and M2
      might promote cucumber yields by mediating bacterial community structure and
      function about nitrogen fixing and urea-N hydrolysis, respectively. Collectively,
      these results revealed that microbial co-inoculants had positive effects on
      cucumber yields. Trait-based integration of different microbial species had
      significant effects on soil properties and bacterial communities. It indicated
      that microbial activity should be considered in the construction of microbial co
      inoculants. This will expand our knowledge in bacteria interaction, deepen
      understanding of microbial inoculants in improving plant performance, and will
      guide microbial fertilizer formulation and application in future.

PMID- 30093898
TI  - Order Parameter in Bacterial Biofilm Adaptive Response.

PMID- 30093899
TI  - Trichinella spiralis Infection Mitigates Collagen-Induced Arthritis via
      Programmed Death 1-Mediated Immunomodulation.
AB  - Helminth infection induces Th2-biased immune responses and inhibitory/regulatory
      pathways that minimize excessive inflammation to facilitate the chronic infection
      of helminth in the host and in the meantime, prevent host hypersensitivity from
      autoimmune or atopic diseases. However, the detailed molecular mechanisms behind
      modulation on inflammatory diseases are yet to be clarified. Programmed death 1
      (PD-1) is one of the important inhibitory receptors involved in the balance of
      host immune responses during chronic infection. Here, we used the murine model to
      examine the role of PD-1 in CD4+ T cells in the effects of Trichinella spiralis
      infection on collagen-induced arthritis (CIA). Mice infected with T. spiralis
      demonstrated higher expression of PD-1 in the spleen CD4+ T cells than those
      without infection. Mice infected with T. spiralis 2 weeks prior to being
      immunized with type II collagen displayed lower arthritis incidence and
      significantly attenuated pathology of CIA compared with those of uninfected mice.
      The therapeutic effect of T. spiralis infection on CIA was reversed by blocking
      PD-1 with anti-PD-1 antibody, associated with enhanced Th1/Th17 pro-inflammatory
      responses and reduced Th2 responses. The role of PD-1 in regulating CD4+ T cell
      differentiation and proliferation during T. spiralis infection was further
      examined in PD-1 knockout (PD-1-/-) C57BL/6 J mice. Interestingly, T. spiralis
      induced alteration of attenuated Th1 and enhanced Th2/regulatory T cell
      differentiation in wild-type (WT) mice was effectively diminished in PD-1-/- mice
      characterized by recovered Th1 cytokine levels, reduced levels of Th2 and
      regulatory cytokines and CD4+CD25+Foxp3+ cells. Moreover, T. spiralis-induced
      CD4+ T cell proliferation suppression in WT mice was partially restored in PD-1-/
      mice. This study introduces the first evidence that PD-1 plays a critical role
      in helminth infection-attenuated CIA in a mouse model by regulating the CD4+ T
      cell function, which may provide the new insights into the mechanisms of helminth
      induced immunomodulation of host autoimmunity.

PMID- 30093900
TI  - Quantitative Measurement of Naive T Cell Association With Dendritic Cells, FRCs,
      and Blood Vessels in Lymph Nodes.
AB  - T cells play a vital role in eliminating pathogenic infections. To activate,
      naive T cells search lymph nodes (LNs) for dendritic cells (DCs). Positioning and
      movement of T cells in LNs is influenced by chemokines including CCL21 as well as
      multiple cell types and structures in the LNs. Previous studies have suggested
      that T cell positioning facilitates DC colocalization leading to T:DC
      interaction. Despite the influence chemical signals, cells, and structures can
      have on naive T cell positioning, relatively few studies have used quantitative
      measures to directly compare T cell interactions with key cell types. Here, we
      use Pearson correlation coefficient (PCC) and normalized mutual information (NMI)
      to quantify the extent to which naive T cells spatially associate with DCs,
      fibroblastic reticular cells (FRCs), and blood vessels in LNs. We measure spatial
      associations in physiologically relevant regions. We find that T cells are more
      spatially associated with FRCs than with their ultimate targets, DCs. We also
      investigated the role of a key motility chemokine receptor, CCR7, on T cell
      colocalization with DCs. We find that CCR7 deficiency does not decrease naive T
      cell association with DCs, in fact, CCR7-/- T cells show slightly higher DC
      association compared with wild type T cells. By revealing these associations, we
      gain insights into factors that drive T cell localization, potentially affecting
      the timing of productive T:DC interactions and T cell activation.

PMID- 30093903
TI  - Optimized Threshold Inference for Partitioning of Clones From High-Throughput B
      Cell Repertoire Sequencing Data.
AB  - During adaptive immune responses, activated B cells expand and undergo somatic
      hypermutation of their B cell receptor (BCR), forming a clone of diversified
      cells that can be related back to a common ancestor. Identification of B cell
      clones from high-throughput Adaptive Immune Receptor Repertoire sequencing (AIRR
      seq) data relies on computational analysis. Recently, we proposed an automated
      method to partition sequences into clonal groups based on single-linkage
      hierarchical clustering of the BCR junction region with length-normalized Hamming
      distance metric. This method could identify clonal sequences with high confidence
      on several benchmark experimental and simulated data sets. However, determining
      the threshold to cut the hierarchy, a key step in the method, is computationally
      expensive for large-scale repertoire sequencing data sets. Moreover, the
      methodology was unable to provide estimates of accuracy for new data. Here, a new
      method is presented that addresses this computational bottleneck and also
      provides a study-specific estimation of performance, including sensitivity and
      specificity. The method uses a finite mixture model fitting procedure for
      learning the parameters of two univariate curves which fit the bimodal
      distribution of the distance vector between pairs of sequences. These
      distributions are used to estimate the performance of different threshold choices
      for partitioning sequences into clones. These performance estimates are validated
      using simulated and experimental data sets. With this method, clones can be
      identified from AIRR-seq data with sensitivity and specificity profiles that are
      user-defined based on the overall goals of the study.

PMID- 30093904
TI  - Inhibition of Lipopolysaccharide- and Lipoprotein-Induced Inflammation by
      Antitoxin Peptide Pep19-2.5.
AB  - The most potent cell wall-derived inflammatory toxins ("pathogenicity factors")
      of Gram-negative and -positive bacteria are lipopolysaccharides (LPS)
      (endotoxins) and lipoproteins (LP), respectively. Despite the fact that the
      former signals via toll-like receptor 4 (TLR4) and the latter via TLR2, the
      physico-chemistry of these compounds exhibits considerable similarity, an
      amphiphilic molecule with a polar and charged backbone and a lipid moiety. While
      the exterior portion of the LPS (i.e., the O-chain) represents the serologically
      relevant structure, the inner part, the lipid A, is responsible for one of the
      strongest inflammatory activities known. In the last years, we have demonstrated
      that antimicrobial peptides from the Pep19-2.5 family, which were designed to
      bind to LPS and LP, act as anti-inflammatory agents against sepsis and endotoxic
      shock caused by severe bacterial infections. We also showed that this anti
      inflammatory activity requires specific interactions of the peptides with LPS and
      LP leading to exothermic reactions with saturation characteristics in calorimetry
      assays. Parallel to this, peptide-mediated neutralization of LPS and LP involves
      changes in various physical parameters, including both the gel to liquid
      crystalline phase transition of the acyl chains and the three-dimensional
      aggregate structures of the toxins. Furthermore, the effectivity of
      neutralization of pathogenicity factors by peptides was demonstrated in several
      in vivo models together with the finding that a peptide-based therapy sensitizes
      bacteria (also antimicrobial resistant) to antibiotics. Finally, a significant
      step in the understanding of the broad anti-inflammatory function of Pep19-2.5
      was the demonstration that this compound is able to block the intracellular
      endotoxin signaling cascade.

PMID- 30093902
TI  - Interleukin (IL)-2 Is a Key Regulator of T Helper 1 and T Helper 2 Cytokine
      Expression in Fish: Functional Characterization of Two Divergent IL2 Paralogs in
      Salmonids.
AB  - Mammalian interleukin (IL)-2 is a cytokine centrally involved in the
      differentiation and survival of CD4+ T helper subsets and CD4+ T regulatory cells
      and in activation of cytotoxic effector lymphocytes. In bony fish, IL2 orthologs
      have been identified with an additional divergent IL2-Like gene on the same locus
      present in several fish species. We report here two divergent IL2 paralogs, IL2A
      and IL2B, in salmonids that originated from the whole genome duplication event in
      this fish lineage. The salmonid IL2 paralogs differ not only in sequence but also
      in exon sizes. The IL-2 isoforms that are encoded have disparate pI values and
      may have evolved to preferentially bind specific IL-2 receptors. Rainbow trout
      IL2 paralogs are highly expressed in thymus, spleen, gills, kidney and intestine,
      important tissues/organs in fish T cell development and function. Their
      expression in peripheral blood leukocytes (PBL) is low constitutively but can be
      upregulated by the mixed leukocyte reaction, by the T cell mitogen
      phytohemagglutinin and by signal mimics of T cell activation (phorbol 12
      myristate 13-acetate and calcium ionophore). Both trout IL-2 isoforms promoted
      PBL proliferation and sustained high-level expression of CD4 and CD8, suggesting
      that trout IL-2 isoforms are T cell growth/survival factors mainly expressed by
      activated T cells. The recombinant proteins for these two trout IL2 paralogs have
      been produced in E. coli and possess shared but also distinct bioactivities. IL
      2A, but not IL-2B, induced IL12P35A1 and CXCR1 expression in PBL. IL-2B had a
      stronger effect on upregulation of the T helper 1 (Th1) cytokine interferon-gamma
      (IFNgamma) and could sustain CD8alpha and CD8beta expression levels.
      Nevertheless, both cytokines upregulated key Th1 (IFNgamma1, IFNgamma2, TNFalpha2
      and IL12) and T helper 2 (Th2) cytokines (IL4/13B1 and IL4/13B2), cytokine and
      chemokine receptors and the antimicrobial peptide cathelicidin-1 but had limited
      effects on T helper 17 cytokines and TGFbeta1 in PBL. They could also enhance PBL
      phagocytosis. These results suggest, for the first time in fish, that IL-2
      isoforms may have an important role in regulating Th1 and Th2 cell development,
      and innate and adaptive host defenses in fish, and shed light on lineage-specific
      expansion, evolution, and functional diversification of IL2 in vertebrates.

PMID- 30093905
TI  - Microglia-Specific Expression of Olfml3 Is Directly Regulated by Transforming
      Growth Factor beta1-Induced Smad2 Signaling.
AB  - Microglia maturation takes place during the postnatal weeks and is characterized
      by the establishment of a unique microglia-specific gene expression pattern.
      Tmem119, Fcrls, Hexb, and Olfml3 have been identified among these microglia
      specific genes. Transforming growth factor beta1 (TGFbeta1) has been reported as
      a critical factor for microglia maturation and maintenance and active TGFbeta
      signaling precedes the inductions of microglial gene expression. In this study,
      we demonstrate Olfml3 expression in adult microglia and further provide evidence
      that TGFbeta1 induces upregulation of Olfml3 expression in postnatal microglia.
      Using chromatin immunoprecipitation and microglia-specific silencing of TGFbeta
      signaling in vitro and in vivo, we in clearly show that Olfml3 is a direct
      TGFbeta1/Smad2 target gene. Together, our data underline the importance of
      TGFbeta1 as a critical regulator of microglia functions and microglia maturation
      and further broaden our understanding of TGFbeta1-mediated effects on the
      resident immune cells of the central nervous system.

PMID- 30093901
TI  - Mass Cytometry for the Assessment of Immune Reconstitution After Hematopoietic
      Stem Cell Transplantation.
AB  - Mass cytometry, or Cytometry by Time-Of-Flight, is a powerful new platform for
      high-dimensional single-cell analysis of the immune system. It enables the
      simultaneous measurement of over 40 markers on individual cells through the use
      of monoclonal antibodies conjugated to rare-earth heavy-metal isotopes. In
      contrast to the fluorochromes used in conventional flow cytometry, metal isotopes
      display minimal signal overlap when resolved by single-cell mass spectrometry.
      This review focuses on the potential of mass cytometry as a novel technology for
      studying immune reconstitution in allogeneic hematopoietic stem cell transplant
      (HSCT) recipients. Reconstitution of a healthy donor-derived immune system after
      HSCT involves the coordinated regeneration of innate and adaptive immune cell
      subsets in the recipient. Mass cytometry presents an opportunity to investigate
      immune reconstitution post-HSCT from a systems-level perspective, by allowing the
      phenotypic and functional features of multiple cell populations to be assessed
      simultaneously. This review explores the current knowledge of immune
      reconstitution in HSCT recipients and highlights recent mass cytometry studies
      contributing to the field.

PMID- 30093906
TI  - Construction of a Protective Vaccine Against Lipopolysaccharide-Heterologous
      Pseudomonas aeruginosa Strains Based on Expression Profiling of Outer Membrane
      Proteins During Infection.
AB  - Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen, which causes
      infectious disease in patients with cystic fibrosis and compromised immunity. P.
      aeruginosa is difficult to eradicate because of its intrinsic resistance to most
      traditional antibiotics as well as acquired resistance mechanisms after decades
      of antibiotic usage. A full understanding of the P. aeruginosa pathogenesis
      mechanisms is necessary for the development of novel prevention and treatment
      strategies. To identify novel vaccine candidates, here we comprehensively
      examined the expression levels of all the known outer membrane proteins in two P.
      aeruginosa strains in a murine acute pneumonia model. OprH was one of the most
      highly expressed proteins during infection. In addition, OprH is known to be
      highly immunogenic and accessible by host proteins. Thus, it was chosen as a
      vaccine candidate. To further identify vaccine candidates, 34 genes highly
      expressed during infection were evaluated for their contributions in virulence by
      testing individual transposon insertion mutants. Among them, fpvA, hasR, and foxA
      were found essential for bacterial virulence and therefore included in vaccine
      construction. Immunization with a mixture of FpvA, HasR, and FoxA rendered no
      protection, however, while immunization by OprH refolded in liposomes elicited
      specific opsonic antibodies and conferred protection against two
      lipopolysaccharide-heterologous P. aeruginosa strains (PA14 and PA103). Overall,
      by studying the expression profile of the P. aeruginosa outer membrane proteins
      during infection, we identified OprH as a potential vaccine candidate for the
      prevention of lung infection by P. aeruginosa.

PMID- 30093907
TI  - Resident Memory-Like Tumor-Infiltrating Lymphocytes (TILRM): Latest Players in
      the Immuno-Oncology Repertoire.
AB  - Resident memory T cells (TRM) are a recently identified subset of long-lived
      memory T cells that are characterized in terms of their unique surface phenotype
      combined with a non-recirculating pattern of localization to non-lymphoid,
      peripheral tissues. TRM have quickly become a key area of focus in understanding
      immune responses to microbial infection in so-called "barrier" tissues, and
      appear to be particularly critical for protection against repeat exposure at the
      same site. More recently, tumor-infiltrating T cells with canonical TRM features
      are being identified in human cancers, in particular cancers of epithelial
      origin, and their presence is broadly found to be associated with favorable long
      term prognosis. Moreover, recent studies have shown that these "resident memory
      like" tumor-infiltrating lymphocytes (referred to herein as TILRM) are uniquely
      activated in melanoma patients undergoing PD-1 directed checkpoint blockade
      therapy. Accordingly, there is much interest at present regarding the biology of
      these cells and their precise role in anti-cancer immunity. Herein, we review the
      current state of the literature regarding TILRM with a specific emphasis on their
      specificity, origins, and relationship to conventional pathogen-specific TRM and
      speculate upon the way(s) in which they might contribute to improved prognosis
      for cancer patients. We discuss the growing body of evidence that suggests TILRM
      may represent a population of bona-fide tumor-reactive T cells and the attractive
      possibility of leveraging this cell population for future immunotherapy.

PMID- 30093909
TI  - Developing New Oligo Probes to Distinguish Specific Chromosomal Segments and the
      A, B, D Genomes of Wheat (Triticum aestivum L.) Using ND-FISH.
AB  - Non-denaturing FISH (ND-FISH) technology has been widely used to study the
      chromosomes of Triticeae species because of its convenience. The oligo probes for
      ND-FISH analysis of wheat (Triticum aestivum L.) chromosomes are still limited.
      In this study, the whole genome shotgun assembly sequences (IWGSC WGA v0.4) and
      the first version of the reference sequences (IWGSC RefSeq v1.0) of Chinese
      Spring (T. aestivum L.) were used to find new tandem repeats. One hundred and
      twenty oligo probes were designed according to the new tandem repeats and used
      for ND-FISH analysis of chromosomes of wheat Chinese Spring. Twenty nine of the
      120 oligo probes produce clear or strong signals on wheat chromosomes. Two of the
      29 oligo probes can be used to conveniently distinguish wheat A-, B-, and D
      genome chromosomes. Sixteen of the 29 oligo probes only produce clear or strong
      signals on the subtelomeric regions of 1AS, 5AS, 7AL, 4BS, 5BS, and 3DS arms, on
      the telomeric regions of 1AL, 5AL, 2BS, 3BL, 6DS, and 7DL arms, on the
      intercalary regions of 4AL and 2DL arms, and on the pericentromeric regions of
      3DL and 6DS arms. Eleven of the 29 oligo probes generate distinct signal bands on
      several chromosomes and they are different from those previously reported. In
      addition, the short and long arms of 6D chromosome have been confirmed. The new
      oligo probes developed in this study are useful and convenient for distinguishing
      wheat chromosomes or specific segments of wheat chromosomes.

PMID- 30093908
TI  - Genome-Wide Analysis of CDPK Family in Foxtail Millet and Determination of
      SiCDPK24 Functions in Drought Stress.
AB  - Plant calcium-dependent protein kinases (CDPKs) were reported to play important
      roles in plant resistance to abiotic stress. Foxtail millet cultivation "H138"
      was used for RNA-seq analysis. The data from drought-induced de novo
      transcriptomic sequences of foxtail millet showed that CDPKs were up- or down
      regulated by drought to different degrees. In this study, 29 foxtail millet CDPKs
      were classified into four subgroups. These genes were unevenly distributed on
      nine foxtail millet chromosomes, and chromosomes 2, 3, and 9 contained the most
      SiCDPK members. Analysis of putative cis-acting elements showed that most foxtail
      millet CDPK genes contained the ABRE, LTR, HSE, MYB, MYC, DRE, CGTCA-motif, and
      TGACG-motif cis-acting elements, which could be activated by abiotic stresses.
      Real-time PCR analysis indicated that 29 SiCDPK genes experienced different
      degrees of induction under drought and ABA stresses. SiCDPK24 had the highest
      expression levels at 6 and 12 h of drought treatment and was chosen for further
      analysis. SiCDPK24 localized to the cell membrane and the nucleus of Arabidopsis
      mesophyll protoplasts. Western blot analysis showed that SiCDPK24 protein had
      autophosphorylation activity. Overexpression of SiCDPK24 in Arabidopsis enhanced
      drought resistance and improved the survival rate under drought stress. It also
      activated the expressions of nine stress-related genes, namely RD29A, RD29B,
      RD22, KIN1, COR15, COR47, LEA14, CBF3/DREB1A, and DREB2A. These genes are
      involved in resistance to abiotic stresses in Arabidopsis. These results indicate
      that foxtail millet CDPK genes play important roles in resisting drought stress.

PMID- 30093910
TI  - Overview of the structure-based non-genomic effects of the nuclear receptor
      RXRalpha.
AB  - The nuclear receptor RXRalpha (retinoid X receptor-alpha) is a transcription
      factor that regulates the expression of multiple genes. Its non-genomic function
      is largely related to its structure, polymeric forms and modification. Previous
      research revealed that some non-genomic activity of RXRalpha occurs via formation
      of heterodimers with Nur77. RXRalpha-Nur77 heterodimers translocate from the
      nucleus to the mitochondria in response to certain apoptotic stimuli and this
      activity correlates with cell apoptosis. More recent studies revealed a
      significant role for truncated RXRalpha (tRXRalpha), which interacts with the
      p85alpha subunit of the PI3K/AKT signaling pathway, leading to enhanced
      activation of AKT and promoting cell growth in vitro and in animals. We recently
      reported on a series of NSAID sulindac analogs that can bind to tRXRalpha through
      a unique binding mechanism. We also identified one analog, K-80003, which can
      inhibit cancer cell growth by inducing tRXRalpha to form a tetramer, thus
      disrupting p85alpha-tRXRalpha interaction. This review analyzes the non-genomic
      effects of RXRalpha in normal and tumor cells, and discusses the functional
      differences based on RXRalpha protein structure (structure source: the RCSB
      Protein Data Bank).

PMID- 30093912
TI  - Switching from a high-fat cellulose diet to a high-fat pectin diet reverses
      certain obesity-related morbidities.
AB  - Background: Reducing caloric intake is a proven intervention for mitigating and
      modulating morbidities associated with overnutrition. Caloric restriction is
      difficult to affect clinically, therefore, dietary interventions that ameliorate
      the adverse consequences of overnutrition in the presence of a high-calorie diet
      would be of value. Methods: Mice were fed an obesogenic diet containing 60% fat +
      10% cellulose (HFC), or a control diet containing 10% fat + 10% cellulose (LFC)
      for 12 wks. Subgroups of mice were then switched from HFC to each of the
      following diets for an additional 5 wks: 1) 60% fat + 10% pectin (HFP), 2) LFC or
      3) 10% fat + 10% pectin (LFP). To test for statistical differences, one-way or
      two-way ANOVAs were used with or without repeated measurements as needed.
      Results: In comparison to HFC, HFP prevented additional weight gain while LFC and
      LFP triggered weight loss of 22.2 and 25.4%, respectively. Mice continued on HFC
      experienced a weight increase of 26% during the same 5 wk. interval. After 12
      wks, HFC decreased mouse locomotion by 18% when compared to control diet, but a
      diet switch to LFC or LFP restored mouse movement. Importantly, HFP, LFC, and LFP
      reduced fasting blood glucose when compared to HFC. Likewise, HFP, LFC and LFP
      improved glucose tolerance and decreased fatty liver by 37.9, 49.8, 53.6 and
      20.2%, 37.2, 43.7%, respectively. Conclusions: Taken together, the results
      indicate that the dietary fiber pectin can mitigate some adverse consequences of
      overnutrition even in the presence of high-fat.

PMID- 30093911
TI  - Virtual memory cells make a major contribution to the response of aged influenza
      naive mice to influenza virus infection.
AB  - Background: A diverse repertoire of naive T cells is thought to be essential for
      a robust response to new infections. However, a key aspect of aging of the T cell
      compartment is a decline in numbers and diversity of peripheral naive T cells. We
      have hypothesized that the age-related decline in naive T cells forces the immune
      system to respond to new infections using cross-reactive memory T cells generated
      to previous infections that dominate the aged peripheral T cell repertoire.
      Results: Here we confirm that the CD8 T cell response of aged, influenza-naive
      mice to primary infection with influenza virus is dominated by T cells that
      derive from the memory T cell pool. These cells exhibit the phenotypic
      characteristics of virtual memory cells rather than true memory cells.
      Furthermore, we find that the repertoire of responding CD8 T cells is constrained
      compared with that of young mice, and differs significantly between individual
      aged mice. After infection, these virtual memory CD8 T cells effectively develop
      into granzyme-producing effector cells, and clear virus with kinetics comparable
      to naive CD8 T cells from young mice. Conclusions: The response of aged,
      influenza-naive mice to a new influenza infection is mediated largely by memory
      CD8 T cells. However, unexpectedly, they have the phenotype of VM cells. In
      response to de novo influenza virus infection, the VM cells develop into granzyme
      producing effector cells and clear virus with comparable kinetics to young CD8 T
      cells.

PMID- 30093914
TI  - Health care seeking behavior for depression in Northeast Ethiopia: depression is
      not considered as illness by more than half of the participants.
AB  - Background: Depression is one of the most disabling and chronic mental illnesses.
      Despite its high burden, many people suffering from depression did not perceive
      that they had a treatable illness and consequently most of them did not seek
      professional help. The aim of this study was to assess the level of professional
      help-seeking behavior and associated factors among individuals with depression.
      Methods and materials: The community-based cross-sectional study was conducted
      among residents of Dessie, Northeast Ethiopia. First, 1165 residents were
      screened for depression using patient health questionnaire and then 226
      individuals who were screened positive for probable depression were interviewed
      with General Help-Seeking Questionnaire to assess the professional help-seeking
      behavior of participants with depression. Major associated variables were
      identified using logistic regression with 95% confidence interval (CI), and
      variables with a p value less than 0.05 were considered statistically
      significant. Results: Among the total participants with depressive symptoms, only
      25.66% of them did seek professional help. Being female [adjusted odds ratio
      (AOR) = 2.769, 95% CI (1.280, 5.99)], current alcohol drinking [AOR = 2.74, 95%
      CI (1.265, 5.940)], co-morbid medical-surgical illness [AOR = 4.49, 95% CI
      (1.823, 11.071)], perceiving depression as illness [AOR = 2.44, 95% CI (1.264,
      4.928)], having moderate depressive symptoms [AOR = 2.54, 95% CI (1.086, 5.928)]
      and moderately severe depressive symptoms [AOR = 7.67, 95% CI (2.699, 21.814)]
      were significantly associated with help seeking behavior of participants.
      Conclusions: Level of professional help-seeking behavior is as low as previous
      studies in different countries. The severity of depressive symptoms, co-morbidity
      of medical-surgical illness, current drinking of alcohol, being female, and
      perceiving depression as illness were significantly associated with professional
      help-seeking behavior for depressive symptoms. Working on mental health literacy
      in the community is important to increase help-seeking behavior.

PMID- 30093915
TI  - Lost in transition? Perceptions of health care among young people with mental
      health problems in Germany: a qualitative study.
AB  - Background: The transitioning of young patients from child and adolescent to
      adult mental health services when indicated often results in the interruption or
      termination of service. The personal views of young service users on current
      clinical practice are a valuable contribution that can help to identify service
      gaps. The purpose of this qualitative study was to explore the perceptions of
      health care of young people with mental health problems in the transition age
      range (16-25 years), and to better understand health behaviour, care needs and
      the reasons for disengaging from care at this point in time. Methods: Seven group
      discussions and three interviews were conducted with 29 young people in this age
      range. Discussions were audio-taped, transcribed verbatim and analysed following
      the reconstructive approach of R. Bohnsack's documentary method. Results: An
      overarching theme and nine subthemes emerged. Participants displayed a
      pessimistic and disillusioned general attitude towards professional mental health
      services. The discussions highlighted an overall concern of a lack of compassion
      and warmth in care. When they come into contact with the system they often
      experience a high degree of dependency which contradicts their pursuit of
      autonomy and self-determination in their current life stage. In the discussions,
      participants referred to a number of unmet needs regarding care provision and
      strongly emphasised relationship issues. As a response to their care needs not
      being met, they described their own health behaviour as predominantly passive,
      with both an internal and external withdrawal from the system. Conclusions:
      Research and clinical practice should focus more on developing needs-oriented and
      autonomy-supporting care practice. This should include both a shift in staff
      training towards a focus on communicative skills, and the development of skills
      training for young patients to strengthen competences in health literacy.

PMID- 30093913
TI  - Vitamin D supplementation and serum heat shock protein 60 levels in patients with
      coronary heart disease: a randomized clinical trial.
AB  - Background: The aim in this study was to investigate the effect of vitamin D
      (25(OH)D3) supplementation on heat shock protein 60 (HSP 60) and other
      inflammatory markers (IL-17, TNF-alpha, PAB) in patients with coronary heart
      disease (CHD). Methods: In this double-blind, randomized clinical trial, we
      recruited 80 male and female patients aged 30-60 with CHD and 25(OH)D3 serum
      levels < 30 ng/ml from Rasool-e-Akram Hospital in Tehran, Iran. Serum levels of
      HSP 60 as primary outcome, and 25(OH)D3, IL-17, TNF-alpha, PAB, lipid profiles
      and parathyroid hormone (PTH) as secondary outcomes were measured at baseline and
      post-intervention. We randomly assigned eligible participants to a placebo group
      (N = 40) or an intervention group (N = 40) (50,000 IU/wk. vitamin D supplement)
      for eight weeks. Results: The results demonstrated that vitamin D supplementation
      resulted in a significant increase in 25(OH) D3 serum levels in the intervention
      group compared to the placebo group (46.86 vs. 7.28 ng/ml). PTH levels decreased
      in the intervention group compared to the placebo group (- 19.81 vs. 2.92 pg/ml)
      after eight weeks of supplementation. Furthermore, we observed a significant
      change in waist circumference (- 0.97 vs. -0.26 cm), fat percentage (-.13 vs.
      0.1%), systolic blood pressure (- 3.85 vs. -2.11 mmHg) and diastolic blood
      presure (- 4 vs. -1.86 mmHg) in the vitamin D group compared to the placebo group
      (all P values < 0.05). Other variables did not significantly change after the
      intervention. Conclusion: Based on our findings, weekly vitamin D supplementation
      of 50,000 IU for eight weeks in patients with CHD resulted in decreased systolic
      and diastolic blood pressure, waist circumference and fat percentage. No
      significant effect on HSP 60, inflammatory markers or lipid profiles was
      observed. Trial registration: IRCT, IRCT201612122365N14. Registered 12 December
      2016.

PMID- 30093917
TI  - Survival probabilities and trends for lip, oral cavity and oropharynx cancers in
      Northern Portugal in the period 2000-2009.
AB  - Background: Oral cancer represents a serious public health problem worldwide. Our
      aim was to analyse the survival probabilities and trends of patients presenting
      with lip, oral cavity and oropharynx cancers, who were residents in the north of
      Portugal. Methods: Using cancer-registry data, we conducted a population-based
      study of lip, oral cavity and oropharynx cancers diagnosed in the period 2000
      2009, among residents in the north of Portugal. Net survival was estimated using
      the Pohar-Perme estimator. Excess hazard ratios (for gender, age group, tumour
      location, stage, residence area and period of diagnosis) were estimated using
      flexible parametric models. Results: A total of 2,947 cases (79.5% males) were
      included of which 18.5% were located on the lip, 56.2% in the oral cavity and
      25.3% in the oropharynx. A large proportion of patients were diagnosed in stages
      III and IV (18.6% and 48.7%, respectively). The 5-year net survival (5yr-NS) for
      all three cancer sites together was 46% (95%CI 44-48), being 88% (95%CI 83-94),
      41% (95%CI 38-43) and 27% (95%CI 23-30) for lip, oral cavity and oropharynx
      cancer, respectively. The 5yr-NS stratified by tumour stage was 84% (95%CI 78-90)
      for stage I, 69% (95%CI 63-76) for stage II, 42% (95%CI 37-47) for stage III and
      19% (95%CI 16-21) for stage IV. When comparing the periods 2000-4 and 2005-9, no
      overall improvements in survival were observed. However, when analysed by stage,
      a significant reduction in the adjusted excess mortality was observed for stages
      II (p = 0.021) and III (p < 0.001). Conclusion: More than half of the oral cavity
      and oropharynx cancers were diagnosed in advanced stages of the disease, having a
      low survival probability. Improvements in survival in the first decade of this
      century were limited to stages II and III, which were the result of changes in
      hospital cancer care practices.

PMID- 30093916
TI  - Nurse-led active surveillance for prostate cancer is safe, effective and
      associated with high rates of patient satisfaction-results of an audit in the
      East of England.
AB  - Introduction: Active surveillance (AS) is an option in the management of men with
      low-stage, low-risk prostate cancer. These patients, who often require prolonged
      follow-up, can put a strain on outpatient resources. Nurses are ideally placed to
      develop advanced roles to help meet this increased demand-a model we have
      utilised since 2014. We set about to comprehensively evaluate our nurse-led AS
      (NLAS) programme. Patients and methods: An audit of patient notes was carried out
      to assess compliance with trust and national guidelines. A questionnaire was
      designed to capture patients' experiences of NLAS. This was piloted and then
      distributed to all patients in our NLAS programme. A second questionnaire was
      designed to assess the views of stakeholders within the department. Results:
      Compliance with various aspects of local guidelines ranged from 88.8% to 100%.
      143 patients are currently in the programme with a mean duration of AS of 37.03
      months. 104 questionnaires were returned. Most of the patients were aware of the
      role of the nurse prior to their visit, and all were happy to meet with a nurse.
      All of the patients indicated their confidence in the nurse monitoring their
      prostate-specific antigen. Among those requiring further investigations, 85.3%
      were happy with the information they received prior to their tests. Overall,
      96.2% were either very satisfied or satisfied with NLAS. All stakeholders held
      positive views about NLAS. Conclusions: NLAS is safe and effective. Patients and
      stakeholders alike held positive views of the programme.

PMID- 30093918
TI  - Accountability in the NHS: the impact on cancer care.
AB  - Accountability of service delivery is becoming increasingly complex and never has
      this been more apparent than in the field of Oncology. Cancer care has an
      unrivalled level of complexity not only in the heterogeneity of management of the
      disease itself but increasingly in the myriad of service providers, specialities,
      policymakers and regulatory bodies overseeing its delivery. The stepwise series
      of changes to NHS structures over recent decades has had an enormous impact on
      our ability to answer key questions which lie at the heart of accountability: who
      is making the key decisions about changes to cancer care delivery? What are these
      reforms achieving? How can they be influenced? It is only through clear and
      transparent decision-making that we may have any hope of implementing, monitoring
      and influencing the effects of evidence-based change. However, with growing
      complexity of service structures and an increasing number of bodies developing
      ambitious and complex strategies, in a context of resource restraint and system
      pressures, it has become very difficult to answer these questions clearly. This
      increasing lack of clarity and transparency around such fundamental questions may
      mean that, despite there being such a pressing need and apparent desire for
      accountability in cancer care, paradoxically we may actually be deviating further
      and further away from this. Perhaps it is time for less complexity and for the
      decision-makers to get back to some fundamental principles which clinicians have
      embraced in evidence-based medicine: what is being done and by whom? Is this
      change beneficial and if not how can we influence change?

PMID- 30093919
TI  - Breath biopsy for early detection and precision medicine in cancer.
AB  - Breath biopsy enables the non-invasive collection and analysis of volatile
      organic compounds (VOCs) in exhaled breath, providing valuable information about
      disease processes occurring in the body. Metabolic changes occur in cancer cells
      at the earliest stages of disease. We discuss progress in the use of breath
      biopsy for discovery of breath-based biomarkers for early detection of cancer,
      and potential applications for breath biopsy in enabling precision medicine in
      cancer.

PMID- 30093921
TI  - Synchronous liver metastases in patients with rectal cancer: can we establish
      which treatment first?

PMID- 30093922
TI  - Progression-free survival as a surrogate endpoint for overall survival in modern
      ovarian cancer trials: a meta-analysis.
AB  - Background: Progression-free survival (PFS) has been adopted as the primary
      endpoint in many randomized controlled trials, and can be determined much earlier
      than overall survival (OS). We investigated whether PFS is a good surrogate
      endpoint for OS in trials of first-line treatment for epithelial ovarian cancer
      (EOC), and whether this relationship has changed with the introduction of new
      treatment types. Methods: In a meta-analysis, we identified summary data [hazard
      ratio (HR) and median time] from published randomized controlled trials. Linear
      regression was used to assess the association between treatment effects on PFS
      and OS overall, and for subgroups defined by treatment type, postprogression
      survival (PPS) and established prognostic factors. Results: Correlation between
      HRs for PFS and OS, in 26 trials with 30 treatment comparisons comprising 24,870
      patients, was modest (r2 = 0.52, weighted by trial sample size). The correlation
      diminished with recency: preplatinum/paclitaxel era, r2= 0.66;
      platinum/paclitaxel, r2= 0.44; triplet combinations, r2= 0.22; biologicals, r2=
      0.30. The median PPS increased over time for the experimental (Ptrend = 0.03) and
      control arms (Ptrend = 0.003). The difference in median PPS between treatment
      arms strongly correlated with the difference in median OS (r2 = 0.83). In trials
      where the control therapy had median PPS of less than 18 months, correlation
      between PFS and OS was stronger (r2 = 0.64) than where the median PPS was longer
      (r2 = 0.48). Conclusions: In EOC, correlation in the relative treatment effect
      between PFS and OS in first-line platinum-based chemotherapy randomized
      controlled trials is moderate and has weakened with increasing availability of
      effective salvage therapies.

PMID- 30093920
TI  - Inflammatory molecules might become both biomarkers and therapeutic targets for
      stroke management.
AB  - Stroke is the fifth leading cause of death and the most frequent cause of
      disability worldwide. Currently, stroke diagnosis is based on neuroimaging;
      therefore, the lack of a rapid tool to diagnose stroke is still a major concern.
      In addition, therapeutic approaches to combat ischemic stroke are still scarce,
      since the only approved therapies are directed toward restoring blood flow to the
      affected brain area. However, due to the reduced time window during which these
      therapies are effective, few patients benefit from them; therefore, alternative
      treatments are urgently needed to reduce stroke brain damage in order to improve
      patients' outcome. The inflammatory response triggered after the ischemic event
      plays an important role in the progression of stroke; consequently, the study of
      inflammatory molecules in the acute phase of stroke has attracted increasing
      interest in recent decades. Here, we provide an overview of the inflammatory
      processes occurring during ischemic stroke, as well as the potential for these
      inflammatory molecules to become stroke biomarkers and the possibility that these
      candidates will become interesting neuroprotective therapeutic targets to be
      blocked or stimulated in order to modulate inflammation after stroke.

PMID- 30093924
TI  - Change in cost and affordability of a typical and nutritionally adequate diet
      among socio-economic groups in rural Nepal after the 2008 food price crisis.
AB  - Diet quality is an important determinant of nutrition and food security and
      access can be constrained by changes in food prices and affordability. Poverty,
      malnutrition, and food insecurity are high in Nepal and may have been aggravated
      by the 2008 food price crisis. To assess the potential impact of the food price
      crisis on the affordability of a nutritionally adequate diet in the rural plains
      of Nepal, data on consumption patterns and local food prices were used to
      construct typical food baskets, consumed by four different wealth groups in
      Dhanusha district in 2005 and 2008. A modelled diet designed to meet household
      requirements for energy and essential nutrients at minimum cost, was also
      constructed using the 'Cost of Diet' linear programming tool, developed by Save
      the Children. Between 2005 and 2008, the cost of the four typical food baskets
      increased by 19% - 26% and the cost of the nutritionally adequate modelled diet
      increased by 28%. Typical food baskets of all wealth groups were low in macro and
      micronutrients. Income data for the four wealth groups in 2005 and 2008 were used
      to assess diet affordability. The nutritionally adequate diet was not affordable
      for poorer households in both 2005 and 2008. Due to an increase in household
      income levels, the affordability scenario did not deteriorate further in 2008.
      Poverty constrained access to nutritionally adequate diets for rural households
      in Dhanusha, even before the 2008 food price crisis. Despite increased income in
      2008, households remain financially unable to meet their nutritional
      requirements.

PMID- 30093923
TI  - Intra-rater reliability of hip abductor isometric strength testing in a standing
      position in older fallers and non-fallers.
AB  - Background: Reduced hip muscle strength has been shown to be a major factor
      related to falls in older persons. However, comprehensive assessment of hip
      abduction strength in the clinical setting is challenging. The aim of this study
      was to investigate the feasibility and intra-rater reliability of a quick and
      simple hip abductor strength test in a functional standing position. Methods:
      Individuals over 65 years of age were recruited from the geriatric department of
      a university hospital and an outpatient clinic. Thirty-two older subjects,
      including 16 fallers (>=1 fall during the last 12 months) and 16 non-fallers were
      included. Maximum voluntary isometric strength (MVIS) and rate of force
      generation (RFG) of the hip abductors of the right leg were evaluated in a
      standing position using a hand-held dynamometer. Two test-sessions were carried
      out. All hip strength values were normalized to participants' weight. Reliability
      was determined using the intra-class correlation coefficient agreement
      (ICCagreement), the standard error of measurement (SEM) and a Bland and Altman
      analysis (BA). Results: All participants completed the strength tests, which took
      a mean 2.47 +/- 0.49 min (one limb). Intra-rater reliability was higher for MVIS
      (0.98[0.95-0.99]) than RFG (ICC = 0.93[0.87-0.97]) for the entire sample. In the
      non-fallers, ICC was 0.98[0.95-1.00] (SEM = 0.08 N.kg- 1) for MVIS and 0.88[0.75
      0.96] for RFG (SEM = 1.34 N.kg-1.s-1). In the fallers, ICC was 0.94[0.89-0.98]
      (SEM = 0.11 N.kg- 1) for MVIS and 0.93[0.84-0.98] (SEM = 1.12 N.kg- 1.s- 1) for
      RFG. The BA plot showed that the MVIS and RFG values did not differ across test
      sessions, showing that no learning effect occurred (no systematic effect). The
      mean differences between test-sessions were larger and the LOA smaller in the
      fallers than in the non-fallers. Conclusion: Assessment of hip strength in a
      standing position is feasible, rapid and reliable. We therefore recommend this
      position for clinical practice. Future studies should investigate the diagnostic
      value of hip abductor strength in standing to discriminate between fallers and
      non-fallers, and to determine if change in strength following a falls prevention
      program reduces the risk of falls.

PMID- 30093926
TI  - Congenital anterior shoulder dislocation in a newborn treated with closed
      reduction.
AB  - Case: This rare case presents an isolated congenital shoulder dislocation in a
      twin delivery, without traumatic delivery. Delivered by emergent cesarean section
      at 33 weeks gestation, the infant presented with a lateral shoulder crease with x
      rays showing anterior and inferior dislocation. Treatment included prompt
      reduction and stabilization, with follow-up ultrasound demonstrating a physeal
      injury. Conclusions: This case report presents the only published congenital
      shoulder dislocation in an infant after an atraumatic twin cesarean delivery.
      Prompt reduction, stabilization, and ultrasound imaging to assess for physeal
      injury is our recommended management for this scenario.

PMID- 30093927
TI  - Technetium-99m pyrophosphate cardiac SPECT in endomyocardial biopsy negative
      cardiac amyloidosis.
AB  - Cardiac amyloidosis is an under-appreciated cause of heart failure. Establishing
      a diagnosis is important because traditional heart failure treatment regimens can
      worsen left ventricular failure in this disease. Endomyocardial biopsy is the
      gold standard for diagnosis; however, scintigraphy with radiolabeled phosphate
      derivatives and cardiac magnetic resonance imaging have been shown to have high
      sensitivity and specificity in diagnosing cardiac amyloidosis. Furthermore,
      cardiac scintigraphy can reliably differentiate amyloid subtypes. We present a
      case of transthyretin-related cardiac amyloidosis with a negative endomyocardial
      biopsy but positive 99m-technetium pyrophosphate single photon emission computed
      tomography scan and cardiac magnetic resonance imaging. We discuss the utility of
      99m-technetium pyrophosphate imaging in cardiac amyloidosis and the role of
      single photon emission computed tomography. Finally, we review the several forms
      of cardiac amyloidosis and how they pertain to cardiac scintigraphy.

PMID- 30093925
TI  - Investigating Tick-borne Flaviviral-like Particles as a Delivery System for Gene
      Therapy.
AB  - Background: Research on the biogenesis of tick-borne encephalitis virus (TBEV)
      would benefit gene therapy. Due to specific arrangements of genes along the TBEV
      genome, its viral-like particles (VLPs) could be exploited as shuttles to deliver
      their replicon, which carries therapeutic genes, to immune system cells.
      Objective: To develop a flaviviral vector for gene delivery as a part of gene
      therapy research that can be expressed in secretable VLP suicidal shuttles and
      provide abundant unique molecular and structural data supporting this gene
      therapy concept. Method: TBEV structural gene constructs of a Swedish Toro strain
      were cloned into plasmids driven by the promoters CAG and CMV and then
      transfected into various cell lines, including COS-1 and BHK-21. Time-course
      sampling of the cells, culture fluid, cell lysate supernatant, and pellet
      specimens were performed. Western blotting and electron microscopy analyses of
      collected specimens were used to investigate molecular and structural processing
      of TBEV structural proteins. Results: Western blotting analysis showed
      differences between promoters in directing the gene expression of the VLPs
      constructs. The premature flaviviral polypeptides as well as mature VLPs could be
      traced. Using electron microscopy, the premature and mature VLP accumulation in
      cellular compartments-and also endoplasmic reticulum proliferation as a virus
      factory platform-were observed in addition to secreted VLPs. Conclusions: The
      abundant virologic and cellular findings in this study show the natural
      processing and safety of inserting flaviviral structural genes into suicidal VLP
      shuttles. Thus, we propose that these VLPs are a suitable gene delivering system
      model in gene therapy.

PMID- 30093928
TI  - Torsion of a giant antimesenteric lipoma of the sigmoid: a rare cause of acute
      abdomen.
AB  - Lipomas of the gastrointestinal tract are uncommon benign tumors of mature
      adipocytes and may occur in any portion along the gut. Depending on location they
      may have a variety of clinical presentations and even simulate malignant
      neoplasms. We report a case of a 58-year-old woman who presented with acute
      pelvic pain. An emergency sonogram detected a hyperechogenic mass in the left
      adnexal region, with no vascularization on Doppler. A computed tomography
      confirmed the hypothesis of a fat containing tumor with signals of torsion. The
      patient underwent laparoscopy which depicted a mass over the antimesenteric side
      of the sigmoid with signs of ischemia and twisted vascular pedicle. The lesion
      was resected, and the microscopy confirmed the diagnosis of lipoma. The
      multidisciplinary team in the emergency room must be aware of these possible
      complications in order to optimize patient care.

PMID- 30093929
TI  - Bilateral hyperdense middle cerebral arteries: Stroke sign or not?
AB  - Hyperdense middle cerebral artery (MCA) is a classic sign of acute thromboembolic
      disease. Simultaneous bilateral occurrence is uncommon and traditionally
      attributed to physiological hemoconcentration or attributable to imaging
      artifact. We present the case of a 71-year-old man whose admission noncontrast
      computed tomography (CT) demonstrated bilateral hyperdense middle cerebral
      arteries without other radiographic evidence of acute stroke. CT angiography
      confirmed bilateral MCA, M1 segment vascular occlusion and follow-up noncontrast
      CT demonstrated MCA territory infarctions.

PMID- 30093930
TI  - Computational Design of Two-Dimensional Perovskites with Functional Organic
      Cations.
AB  - Two-dimensional (2D) halide perovskites are a class of materials in which 2D
      layers of perovskite are separated by large organic cations. Conventionally, the
      2D perovskites incorporate organic cations as spacers, but these organic cations
      also offer a route to introduce specific functionality in the material. In this
      work, we demonstrate, by density functional theory calculations, that the
      introduction of electron withdrawing and electron donating molecules leads to the
      formation of localized states, either in the organic or the inorganic part.
      Furthermore, we show that the energy of the bands located in the organic and
      inorganic parts can be tuned independently. The organic cation levels can be
      tuned by changing the electron withdrawing/donating character, whereas the energy
      levels in the inorganic part can be modified by varying the number of inorganic
      perovskite layers. This opens a new window for the design of 2D perovskites with
      properties tuned for specific applications.

PMID- 30093932
TI  - Brooke-Spiegler Syndrome.

PMID- 30093931
TI  - Computational Screening of Metal-Organic Frameworks for Membrane-Based CO2/N2/H2O
      Separations: Best Materials for Flue Gas Separation.
AB  - It has become a significant challenge to select the best metal-organic frameworks
      (MOFs) for membrane-based gas separations because the number of synthesized MOFs
      is growing exceptionally fast. In this work, we used high-throughput
      computational screening to identify the top MOF membranes for flue gas
      separation. Grand canonical Monte Carlo and molecular dynamics simulations were
      performed to assess adsorption and diffusion properties of CO2 and N2 in 3806
      different MOFs. Using these data, selectivities and permeabilities of MOF
      membranes were predicted and compared with those of conventional membranes,
      polymers, and zeolites. The best performing MOF membranes offering CO2/N2
      selectivity > 350 and CO2 permeability > 106 Barrer were identified. Ternary
      CO2/N2/H2O mixture simulations were then performed for the top MOFs to unlock
      their potential under industrial operating conditions, and results showed that
      the presence of water decreases CO2/N2 selectivity and CO2 permeability of some
      MOF membranes. As a result of this stepwise screening procedure, the number of
      promising MOF membranes to be investigated for flue gas separation in future
      experimental studies was narrowed down from thousands to tens. We finally
      examined the structure-performance relations of MOFs to understand which
      properties lead to the greatest promise for flue gas separation and concluded
      that lanthanide-based MOFs with narrow pore openings (<4.5 A), low porosities
      (<0.75), and low surface areas (<1000 m2/g) are the best materials for membrane
      based CO2/N2 separations.

PMID- 30093933
TI  - Cell-free DNA in blood and urine as a diagnostic tool for bladder cancer: a meta
      analysis.
AB  - OBJECTIVE: To assess the diagnostic performance of cell-free DNA assays in the
      detection of bladder cancer. PATIENTS AND METHODS: The quality of the studies
      included in this meta-analysis was assessed using the Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS-2) tool. Statistical analyses were performed
      using the software RevMan 5.3 and Stata 14.0. We assessed the pooled sensitivity
      and specificity, positive/negative likelihood ratios (PLRs/NLRs), diagnostic odds
      ratios (DORs), and corresponding 95% confidence intervals (95% CIs). Summary
      receiver operating characteristic curve (ROC curve) and area under the curve
      (AUC) were used to summarize the overall test performance. Heterogeneity and
      publication bias were also examined. RESULTS: Eleven studies included 802 bladder
      cancer patients and 668 controls met the eligibility criteria. The overall
      diagnostic accuracy was measured as follows: sensitivity 0.71 (95% CI = 0.64
      0.77), specificity 0.78 (95% CI = 0.70-0.85), PLR 3.3 (95% CI = 2.4-54.5), NLR
      0.37 (95% CI = 0.30-0.46), DOR 9 (95% CI = 6-14), and AUC 0.80 (95% CI = 0.77
      0.83). Subgroup analysis suggested that ethnicity significantly accounted for the
      heterogeneity of specificity. The Deeks' funnel plot asymmetry test (P = 0.97)
      suggested no potential publication bias. CONCLUSIONS: Cell-free DNA has a high
      diagnostic value in bladder cancer.

PMID- 30093934
TI  - Gankyrin as a potential target for tumor therapy: evidence and perspectives.
AB  - Gankyrin (also known as PSMD10 or p28GANK), engages in diverse biological
      processes, including cellular growth, proliferation and invasion. Several studies
      have demonstrated that Gankyrin is a candidate oncogene. In parallel, the
      dysregulation of Gankyrin has been observered in a variety of human cancer.
      Overexpression of Gankyrin is involved in tumor initiation and progression by
      regulating several signaling pathways that control cell-cycle process, cell
      growth, apoptosis, et al. On the contrary, downregulation of Gankyrin
      significantly inhibits cell growth, proliferation and metastasis. Therefore,
      Gankyrin appears to be a potential target for tumor therapy. Herein, this review
      summarizes the current knowledge in understanding the biological functions and
      oncogenic role of Gankyrin in human cancers from the perspective of clinical
      pathological significances, aiming to provide guidance for the development of
      Gankyrin-targeted therapy.

PMID- 30093936
TI  - Valproic acid regulates Ang II-induced pericyte-myofibroblast trans
      differentiation via MAPK/ERK pathway.
AB  - Myocardial fibrosis (MF) plays an important part in cardiovascular diseases. The
      main cytological characteristics of MF is the increased number of myofibroblasts,
      which have multiple sources such as EMT, EndMT, myeloid progenitors, monocytes,
      and fibrocytes. Recent data showed that pericytes may represent a major source of
      myofibroblasts in kidney fibrosis. Valproic acid (VPA) is a kind of short-chain
      fatty acid. It was reported in recent studies that VPA regulates gene expression
      and influences various signal pathways. HDACs inhibitors can hinder the growth of
      tumor cells and differentiation of stem cells. And little is known about the
      effects of HDACs inhibitors on myofibroblasts transdiffererntiaton. This study
      focused on the role of HDACs in pericyte-myofibroblast trans-differentiation and
      how HDACs inhibitor VPA influenced proliferation, migration, viability and
      myofibroblast trans-differentiation of pericytes for the first time. Rat cardiac
      fibrosis model was induced by Ang II. Immunohistochemistry was employed to
      examine cardiac fibrosis and flow cytometry was used to analyze whether
      inflammatory cells involve VPA-induced trans-differentiation. Pericytes
      proliferation, migration and differentiation to myofibroblasts were performed to
      examine the role of VPA on pericyte trans-differentiation. Immunoblot and qPCR
      were applied to identify the signal transduction involving in VPA-induced trans
      differentiation. In vivo study showed that HDAC inhibitor VPA blocks cardiac
      fibrosis, and inflammation inhibition was not involved in this process. VPA
      treatment inhibited Ang II pericyte proliferation, migration and
      transdifferentiation to myofibroblast. Furthermore, the inhibition of alpha-SMA
      expression by VPA was related to reduce phosphorylation of ERK, and a
      pharmacological inhibitor of MEK suppressed Ang II-induced alpha-SMA expression.
      HDAC4 knockdown resulted in inhibiting Ang II-mediated alpha-SMA expression as
      well as the phosphorylation of ERK. Moreover, the inhibitors of protein
      phosphatase 2A and 1 (PP2A and PP1) restored the Ang II-stimulated alpha-SMA
      expression from the inhibitory effect of VPA. Together, the current data indicate
      that the differentiation of pericytes to myofibroblasts is HDAC4 dependent and
      requires phosphorylation of ERK.

PMID- 30093935
TI  - Resveratrol alleviates sepsis-induced acute lung injury by suppressing
      inflammation and apoptosis of alveolar macrophage cells.
AB  - Sepsis is a major cause of death in intensive care units. The purpose of this
      study was to investigate the effect of resveratrol (RSV) on sepsis-induced acute
      lung injury (ALI). The underlying molecular mechanisms were deciphered by both in
      vitro and in vivo experiments. Polymicrobial sepsis was induced in C57BL/6 mice
      by cecal ligation and puncture (CLP). RSV pretreatment significantly attenuated
      CLP-induced acute lung injury, which was associated with enhanced expression of
      VEGF-B. The protective properties of RSV were assayed in lipopolysaccharide (LPS)
      stimulated MH-S cells. We determine that RSV administration inhibited the
      increased production of TNF-alpha, IL-6, and IL-1beta in LPS-stimulated MH-S
      cells, which was associated with inhibition of the nuclear factor-kappaB, P38,
      and ERK signaling pathways. We also provide evidence that RSV administration
      reduced LPS-induced apoptosis of MH-S cells by altering the unbalance of Bax/Bcl
      2 and inhibiting LPS-induced autophagy. The inhibitory effects of RSV on cytokine
      levels and apoptosis of alveolar macrophages were both blocked by VEGF-B siRNA.
      Furthermore, RSV administration regulated LPS-induced C5aR and C5L2 expression,
      revealing an additional mechanism underlying RSV's anti-inflammatory and anti
      apoptosis effects. Collectively, these results demonstrated that RSV was able to
      protect against sepsis-induced acute lung injury by activating the VEGF-B
      signaling pathway.

PMID- 30093937
TI  - SiRNA silencing of VEGF, IGFs, and their receptors in human retinal microvascular
      endothelial cells.
AB  - Vascular endothelial growth factor (VEGF) is a potent mitogen that regulates
      proliferation, migration, and tube formation of endothelial cells (EC). VEGF has
      recently become a target for severe retinopathy of prematurity (ROP) therapy. We
      tested the hypothesis that a specific VEGF isoform and/or receptor acts
      synergistically with insulin-like growth factor (IGF)-I to alter normal retinal
      microvascular EC angiogenesis and RNA interference can be used to reverse VEGF
      effects. We used small interfering RNA (SiRNA) transfection to target VEGF
      isoforms, IGFs, and their receptors in human retinal microvascular endothelial
      cells (HRECs). Media was collected at 24 and 48 hours post transfection for
      measurement of VEGF, sVEGFR-1 and IGF-1 levels; and HRECs were assessed for
      migration, tube formation, VEGF signaling genes, oxidative stress, and immune
      reactivity. At 24 hours post transfection VEGF increased with VEGFR-2; sVEGFR-1
      decreased with VEGF165, VEGFR-2, and IGF-1R; and IGF-I increased with VEGF189,
      VEGFR-1, IGF-2R, IGF+VEGF165, and IGF+VEGF121. IGF-I transfection with each VEGF
      isoform reduced sphere- forming and migration capacities with robust upregulation
      of caspase-9, COX-2, MAPK, PKC, and VEGF receptors. At 48 hours, the effects were
      reversed with a majority of genes downregulated, except with IGF-I and NP-1
      transfection. Using RNA interference for targeted inhibition of VEGF isoforms in
      conjunction with IGF-I may be preferable for suppression of HREC overgrowth in
      vasoproliferative retinopathies such as ROP.

PMID- 30093938
TI  - Prognosis of patients with TX stage differentiated thyroid cancer: propensity
      scored matching analysis of the SEER database 2004-2013.
AB  - In differentiated thyroid cancer (DTC), TX stage is defined as 'primary tumour
      cannot be assessed'. The prognosis of patients with TX stage remains unclear. The
      aim of this study was to investigate the prognosis of TX stage and provide a
      perspective on treatment guidelines. We investigated a large cohort of DTC
      patients from the Surveillance, Epidemiology, and End Results database between
      2004 and 2013. Patient mortality was examined by Kaplan-Meier analyses with log
      rank tests and Cox proportional hazards regression analyses. The rate of cancer
      specific mortality per 1000 person-years for patients with TX stage was higher
      than for patients with T1-T3 stage, but lower than for patients with T4 stage.
      The all-cause mortality per 1000 person-years for TX stage patients was also
      higher than for T1-T3 stage patients, but lower than for T4 stage patients. TX
      stage showed significant risk for cancer-specific mortality compared to T1 and T4
      stages, but not T2 and T3 stages, after adjusting for influential risk factors.
      TX stage patients showed no significant risk for all-cause mortality compared to
      T2-T3 stage patients, but were different than T1 and T4 stage patients. These
      results provide new implications for the treatment of TX stage DTC patients.

PMID- 30093939
TI  - Diabetes aggravates acute pancreatitis possibly via activation of NLRP3
      inflammasome in db/db mice.
AB  - Clinical studies have confirmed that patients with diabetes had an elevated risk
      of acute pancreatitis (AP) and diabetes was associated with increased severity
      and mortality in patients with AP. However, these studies failed to prove a cause
      and-effect relationship between diabetes and AP. In the present study, we for the
      first time have evaluated the effects of diabetes on AP by adopting a type 2
      diabetes animal model db/db mice and investigated the possible underlying
      mechanisms. The results showed that in comparison to wide type (WT) mice, db/db
      mice showed exacerbated pancreatic and pulmonary injuries, elevated serum amylase
      and lipase levels, increased myeloperoxidase (MPO) expressions in pancreatic and
      pulmonary tissues as well as increased apoptotic acinar cells after AP induction.
      Furthermore, we observed that NLRP3 inflammasome in pancreatic tissues was
      remarkably activated in db/db mice compared with WT mice. In addition, we also
      found that diabetes could increase the susceptibility of mice to AP. Taken
      together, our results indicated that diabetes could predispose and aggravate the
      disease severity of AP potentially via promoting the activation of NLRP3
      inflammasome pathway.

PMID- 30093940
TI  - Exosomes derived from human umbilical cord mesenchymal stem cells alleviate
      inflammatory bowel disease in mice through ubiquitination.
AB  - Exosomes released from mesenchymal stem cells (MSCs) have an anti-inflammatory
      effect and can repair tissue injuries. Ubiquitination plays an important role in
      the regulation of various biological functions, including the regulation of
      inflammation. However, it remains unknown whether exosomes from human umbilical
      cord mesenchymal stem cells (hucMSC-ex) may cure the mice of DSS-induced
      inflammatory bowel disease (IBD) through the ubiquitin modification. In this
      study, we aimed to investigate the therapeutic effect and probe the mechanism
      relating to ubiquitination underlying the hucMSC-ex treatment in DSS-induced IBD
      of mice. HucMSC-ex significantly improved the symptoms of IBD in mice. In the IBD
      group, the gene expression levels of TNF-alpha, IL-1beta, IL-6, NAe1, E2M and
      Uba3 dramatically increased while those of IL-10 and IP-10 decreased. The gene
      expression level in the group of hucMSC-ex treatment was adversed to that in the
      group of IBD. In the hucMSC-ex treated group, western blot results showed that
      the protein expressions of K48, K63 and FK2 have significantly decreased.
      Compared with that in the IBD mice, the mice treated by hucMSC-ex could recover
      the integrity of tissue structure. Our results indicated that exosomes from
      hucMSCs have profound effects on alleviating DSS-induced IBD and may exert their
      function by regulating the ubiquitin modification level.

PMID- 30093941
TI  - Edaravone ameliorates experimental autoimmune thyroiditis in rats through HO-1
      dependent STAT3/PI3K/Akt pathway.
AB  - Autoimmune thyroiditis is among the most prevalent of all the autoimmunities in
      population. It is characterized as both cellular immune responses with T, B cells
      infiltrating to the thyroid gland followed by hypothyroidism as a result of
      destruction of the thyroid follicles and fibrous replacement of the parenchymal
      tissue, as well as immune response for TPO and Tg-antibody production.
      Experimental autoimmune thyroiditis (EAT) has been proven to be an ideal model to
      study autoimmune thyroiditis. In the present study, we induced an EAT model in
      rats and examined the effect of edaravone, a hydroxyl radical scavenging agent,
      on EAT severity and explored the mechanism. The results showed that edaravone
      reduced the severity score of thyroiditis dose-dependently and the levels of
      serum TPOAb, TgAb, T3 and T4. Edaravone significantly decreased the mRNA level of
      IL-17, but increased the mRNA level of IL-10, IL-4, TNF-alpha and IFN-gamma. EAT
      model significantly induced oxidative stress, which was inhibited by the
      treatment of 10 mg/kg, 20 mg/kg or 40 mg/kg of edaravone. The EAT model
      significantly increased the Akt and STAT3 phosphorylation, but when rats were
      treated with 20 mg/kg or 40 mg/kg edaravone, they were significantly inhibited.
      The HO-1 expression was greatly increased by 20 mg/kg or 40 mg/kg edaravone. The
      PI3K inhibitor LY294002, Akt inhibitor triciribine or STAT3 inhibitor WP1066 all
      significantly decreased the severity score of thyroiditis in the EAT model group,
      while the HO-1 inhibitor ZnPP-IX increased the severity score of thyroiditis.
      These results confirm the invlovment of ROS and HO-1-dependent STAT3/PI3K/Akt
      pathway in the process of Hashimoto's thyroiditis and suggest the potential usage
      of edaravone in the therapy of it.

PMID- 30093942
TI  - pre-B cell colony enhancing factor negatively regulates Na+ and fluid transport
      in lung epithelial cells.
AB  - : This study was undertaken to investigate the effect of pre-B cell colony
      enhancing factor (PBEF) on Na+ and fluid transport in lung epithelial cells.
      METHODS: Type 1 and 2 cells were isolated from lung epithelium. After hypoxia
      reoxygenation treatment, the primary cell cultures were transfected with a
      plasmid over-expressing PBEF. Sodium-potassium ATPase (NKA), epithelial sodium
      channel (ENaC), type I cell marker rT140, surfactant protein (SP) and PBEF
      protein were analyzed at mRNA and protein levels using PCR and Western blot
      analysis. Immunofluorescence assays showed type 1 and 2 cells were successfully
      isolated. After the transfection with PBEF over-expression vector, PBEF and RTI40
      levels were increased, while ENaC and SP as well as NKA, were decreased in both
      cells. It is clear that PBEF negatively regulates the expression of ENaC and NKA
      in the Na+ and fluid transport in lung epithelial cells.

PMID- 30093943
TI  - The molecular mechanism and clinical significance of LDHA in HER2-mediated
      progression of gastric cancer.
AB  - OBJECTIVE: The use of human epidermal growth factor receptor-2 (HER2) as a
      biomarker for gastric cancer (GC) has greatly helped some patients receive
      benefit from HER2-targeted therapy. However, the correlation between HER2 and
      other biochemical markers is unclear. The aim of this study was to examine the
      relationship between HER2 and lactate dehydrogenase A (LDHA) in GC tissues and GC
      cells. METHODS: The correlation between clinicopathological features and HER2 was
      analyzed in 179 cases of GC. The expression of HER2 and LDHA was examined by
      immunohistochemical staining in 12 pairs of GC tissues and by western blotting in
      seven pairs of fresh GC tissues and adjacent normal tissues. Wound healing,
      transwell migration assay, quantitative real-time reverse-transcription
      polymerase chain reaction (RT-PCR), and LDH activity assays were performed with
      GC cells. RESULTS: HER2 expression and serum LDH levels were closely correlated
      (P = 0.027) in 179 GC patient cases. Immunohistochemical staining demonstrated a
      positive correlation between HER2 and LDHA in 12 pairs of GC tissues (P =
      0.0308). Knocking down LDHA suppressed cell migration and invasion in GC cells.
      In addition, HER2 positively regulated hypoxia-inducible factor-1alpha (HIF
      1alpha) and LDHA. Furthermore, the expressions of HER2, HIF-1alpha, and LDHA were
      consistent in 5/7 pairs of fresh GC tissues and adjacent normal tissues as well
      as in GC cell lines. CONCLUSIONS: The HER2-HIF-1alpha-LDHA axis may serve as the
      basis for new methods and strategies for the treatment of GC.

PMID- 30093945
TI  - Celastrol aggravates LPS-induced inflammation and injuries of liver and kidney in
      mice.
AB  - Sepsis, a life-threatening syndrome with uncontrolled inflammatory response,
      causes high morbidity and mortality worldwide. Currently, satisfactory treatments
      on sepsis are still lacking in clinic. Thus, new therapeutic strategies are
      urgently required. Recently, celastrol, a pentacyclic triterpene extracted from
      the traditional Chinese medicine Tripterygium Wilfordi plant, attracted great
      interest for its properties of anti-inflammation, anti-oxidative stress, and
      metabolism remodeling. However, the effect of celastrol on sepsis is still
      unclear. In this study, we investigated the effect of celastrol on
      lipopolysaccharides (LPS)-induced inflammation and organ injuries in mice.
      Following celastrol pretreatment, mice showed increased mortality rate and
      aggravated inflammation evidenced by further enhanced inflammatory markers of IL
      6, IL-1beta, TNF-alpha, IL-18, MCP-1, and ICAM-1 in circulation, liver, and
      kidney after LPS treatment. The serum levels of ALT, AST, and LDH were further
      increased in parallel with the deteriorated liver morphological damage (H&E) and
      oxidative stress in celastrol-treated mice, indicating an aggravated liver
      injury. In kidney, the expressions of tubular injury markers of kidney injury
      molecule-1 (KIM-1) and gelatinase-associated lipocalin (NGAL) were further
      upregulated along with higher levels of blood urea nitrogen (BUN), creatinine
      (Cr), and MDA in celastrol-treated mice. These findings not only indicated a
      detrimental role of celastrol therapy in LPS-induced inflammation and organ
      injuries but also suggested the restriction of celastrol usage in sepsis
      patients.

PMID- 30093944
TI  - Comparative study of nanostructured carriers of calcium phosphate and magnesium
      phosphate loaded with SRT1720 for the protection of H2O2-induced senescent
      endothelium.
AB  - Nanostructured calcium phosphate (CaP) and magnesium phosphate (MgP) are
      promising for the application as the nanocarriers in drug delivery. However, the
      difference between CaP and MgP nanocarriers in drug delivery is rarely
      investigated. In this work, we comparatively investigated nanostructured CaP, MgP
      and calcium magnesium phosphate (CMP) for the delivery of SRT1720, which is a
      silent information regulator (SIRT1) specific activator with pro-angiogenic and
      anti-aging properties in response to hydrogen peroxide (H2O2)-induced endothelial
      senescence. The protection of SRT1720-loaded CaP nanospheres, MgP nanosheets and
      CMP microspheres on the H2O2-induced senescent endothelium was examined by using
      human umbilical vein endothelial cells (HUVECs), demonstrating the improved cell
      viability, anti-aging, tube formation and migration. In addition, the SRT1720
      loaded CaP nanospheres, MgP nanosheets and CMP microspheres can rescue the
      impaired angiogenic potential of HUVECs via activation of Akt/eNOS/VEGF pathway.
      The SRT1720-loaded MgP nanosheets and CMP microspheres have a similar protective
      effect compared with the pure SRT1720, while the SRT1720-loaded CaP nanospheres
      decrease the protective capability of SRT1720. These results lead us to figure
      out both MgP nanosheets and CMP microspheres are suitable and effective delivery
      for SRT1720 and this system can be further applied in vivo treatment.

PMID- 30093946
TI  - The change of synovial fluid proteome in rabbit surgery-induced model of knee
      osteoarthritis.
AB  - The aims of this study were to explore the change of synovial fluid (SF) proteome
      in a knee osteoarthritis (KOA) rabbit model, and to provide a new target for the
      treatment of knee osteoarthritis at the proteomic level. Sixteen New Zealand
      rabbits were randomly and equally divided into two groups. Group A rabbits were
      subjected to right anterior cruciate ligament transection (ACLT), while group B
      rabbits were subjected to sham ACLT. Six weeks later, the proteomes of knee joint
      SF from group A and B rabbits were analyzed using a label-free quantitative
      proteomic analysis method. We extracted 944 relevant items from GO BlastGO2 for
      the 23 proteins differentially expressed between the two groups. The final
      annotation results were 23 protein sequences annotated by 462 GO items. According
      to the KEGG gene database of rabbit protein sequences, as well as annotation of
      the KO numbers of homologous/similar proteins to the relevant 64 KEGG pathways,
      we extracted the sequences of 16 significantly differently expressed proteins
      among the relevant 64 KEGG messages/metabolism pathways. These included
      adiponectin, pyruvate kinase, bisphosphoglycerate mutase, HtpG/heat shock
      proteins, hemoglobin subunit alpha-1 2, VCP (CDC48), 14-3-3 protein
      beta/theta/zeta, and ferritin heavy chain, whose levels were decreased in group
      A. The other proteins were fibrinogen alpha/beta/gamma chain, carboxylesterase 2,
      paraoxonase/arylesterase 1, apolipoprotein A-I, immunoglobulin heavy chain, and
      transferrin, whose levels were increased in group B. The identified
      differentially expressed proteins indicate the change of SF proteomic expression
      in KOA and may provide protein targets for treating this condition.

PMID- 30093947
TI  - Effects of human amnion-derived mesenchymal stem cells and conditioned medium in
      rats with sclerosing cholangitis.
AB  - Mesenchymal stem cells (MSCs) represent a valuable cell source in regenerative
      medicine, and large numbers of MSCs can be isolated from the amnion
      noninvasively. Sclerosing cholangitis is a chronic cholestatic disease and
      characterized by progressive biliary destruction leading to cirrhosis. Many
      factors are involved in the development of sclerosing cholangitis; however,
      effective medical therapy is not established. We investigated the effects of
      human amnion-derived MSCs (hAMSCs) and conditioned medium (CM) obtained from
      hAMSC cultures in rats with sclerosing cholangitis. Sclerosing cholangitis was
      induced via the intragastric administration of 100 mg/kg alpha
      naphthylisothiocyanate (ANIT) twice weekly for 4 weeks. One million hAMSCs or 200
      MUL of CM were intravenously administered on days 15 and 22. Rats were sacrificed
      on day 29 and evaluated via histological, immunohistochemical, and mRNA
      expression analyses. hAMSC transplantation and CM administration significantly
      improved the histological score. In addition, these two interventions
      significantly improved biliary hyperplasia, peribiliary fibrosis, and
      inflammation in Glisson's sheath. Accordingly, CK19, MMP-9, and TNF-alpha, and
      MCP-1 expression in the liver was also decreased by hAMSC and CM administration.
      In conclusion, hAMSC and CM administration ameliorated biliary hyperplasia,
      peribiliary fibrosis, and inflammation in a rat model of sclerosing cholangitis.
      hAMSCs and CM may represent new modalities for treating sclerosing cholangitis.

PMID- 30093948
TI  - Urinary proteomics analysis based on mass spectrometry and identification of
      therapeutic targets of Shenkangling interventions in rats with adriamycin
      nephropathy using iTRAQ.
AB  - OBJECTIVE: The isobaric tags for relative and absolute quantification (iTRAQ)
      technique for proteomic analysis was employed to identify diagnostic markers and
      therapeutic targets of Shenkangling intervention or prednisone tablets in rats
      with adriamycin nephropathy (AN). METHODS: Fifty healthy, clean-grade Sprague
      Dawley rats were selected, with 10 rats in the normal group and the remaining 40
      rats receiving a tail vein injection of 5.5 mg/kg of adriamycin (ADR) to induce
      AN. Treatment began 1 week later. The normal group received gastric
      administration of normal saline. Forty rats with induced AN were further randomly
      divided into the AN modeling group (n = 10), AN modeling + prednisone treatment
      group (n = 10), AN modeling + Shenkangling intervention group (n = 10), and AN
      modeling + prednisone + Shenkangling intervention group (n = 10). iTRAQ was
      employed in combination with mass spectrometry to analyze the differentially
      expressed proteins in the urine after 3 weeks of treatment (in the fourth week of
      the experiment). RESULTS: Compared with normal rats, AN rats had 6 down-regulated
      proteins and 1 upregulated protein. Compared with AN rats, prednisone rats had 2
      down-regulated and 6 upregulated proteins. Compared with AN rats, combined
      treatment rats had 2 down-regulated and 8 upregulated proteins. Compared with the
      AN model group, the Shenkangling treatment group had 3 down-regulated and 9
      upregulated proteins. Gro, Afamin, Cystatin-related protein 2, Afamin, and
      isoform CRA_a were considered diagnostic markers of primary nephrotic syndrome
      (PNS). Telomerase was considered the therapeutic target of prednisone. Urinary
      protein 2, Apolipoprotein A-II, 45 kDa calcium-binding protein, Vitronectin, and
      Osteopontin were the therapeutic targets of the Shenkangling intervention.
      Afamin, isoform CRA_a, Apolipoprotein A-IV, Coagulation factor XII, Prolactin
      induced protein, and Coagulation factor XII were the therapeutic targets of the
      Shenkangling intervention combined with prednisone. CONCLUSION: The feasibility
      of urinary proteomics analysis in rats using a large number of proteins with
      finite molecular weights is controversial. The markers screened in this study may
      be of clinical value for the diagnosis and treatment of nephropathy. However,
      these findings should be confirmed in future cohort studies.

PMID- 30093949
TI  - Bioinformatics-based analysis of the involvement of AC005550.3, RP11-415D17.3,
      and RP1-140K8.5 in homocysteine-induced vascular endothelial injury.
AB  - This study aimed to explore the role of certain genes and long non-coding RNAs
      (lncRNAs) in homocysteine (HCY)-induced vascular endothelial injury. HUVECs were
      treated with HCY, then cell cycle and apoptosis were analyzed by flow cytometry.
      HUVECs were then sequenced and analyzed using bioinformatics, with a focus on
      differentially expressed genes/lncRNA (DEGs/DEL), protein-protein interaction
      (PPI), functional enrichment analyses, and lncRNA-target prediction. Although HCY
      did not affect the cell cycle, it significantly increased the number of apoptotic
      cells. In total, 382 DEGs and 147 DELs were identified; DEGs such as CD34, FGF2,
      and SERPINE1 were the hub nodes in the PPI network, in addition to being the
      targets of AC005550.3, RP11-415D17.3, and RP1-140K8.5, respectively. Functional
      enrichment analysis showed that the targets of downregulated AC005550.3 and RP11
      415D17.3 were significantly enriched in blood vessel development and those of
      upregulated RP1-140K8.5 were enriched in fibrinolysis. RT-qPCR showed that the
      mRNA levels of AC005550.3, RP11-415D17.3, and RP1-140K8.5 were consistent with
      the results predicted by our bioinformatics analysis. In conclusion,
      downregulated AC005550.3 and RP11-415D17.3 targeting CD34 and FGF2 and
      upregulated RP1-140K8.5 targeting SERPINE1 may play an important role in HCY
      induced vascular endothelial injury by regulating blood vessel development and
      fibrinolysis, respectively.

PMID- 30093950
TI  - Uremia induces upregulation of cerebral tissue oxidative/inflammatory cascade,
      down-regulation of Nrf2 pathway and disruption of blood brain barrier.
AB  - Chronic kidney disease (CKD) results in various central nervous systems (CNS)
      disorders including cognitive dysfunction, depression, anxiety, movement
      disorders, seizures and encephalopathy. Uremic retention products, oxidative
      stress, inflammation and impaired blood-brain barrier have been implicated as the
      major mediators of CKD-induced CNS disorders. However, mechanisms of CKD-induced
      cerebral tissue oxidative stress, inflammation and impaired blood brain barrier
      have not been fully elucidated and were explored. Male Sprague Dawley rats
      underwent sham operation or 5/6 nephrectomy and were observed for 10 weeks.
      Arterial pressure, body weight, and renal function were monitored. Under general
      anesthesia the animals' cerebral cortex was harvested. Nuclear translocations of
      NF-kappaB and Nrf2 and their key target gene products, neuronal, endothelial and
      inducible NO synthase (NOS) isoforms, markers of oxidative, nitrosative and
      myeloperoxidase reactions, fibrosis mediators and key protein constituents of
      capillary endothelial junctional complex were determined by Western blot
      analysis. The CKD rats exhibited reduced body weight, hypertension, elevated
      serum urea and creatinine concentrations. Compared to control group cerebral
      cortex of the CKD group showed activation (increased nuclear translocation) of NF
      kappaB, elevation of pro-oxidant and pro-inflammatory molecules, diminished
      nuclear translocation of Nrf2 and expression of cytoprotective antioxidant
      molecules and depletion of the key protein constituents of endothelial junctional
      complex. In conclusion CKD results in the cerebral tissue activation of
      inflammatory and oxidative pathways, inhibition of antioxidant and cytoprotective
      system and erosion of cerebral capillary junctional complex, events that
      contribute to CNS dysfunction and impaired blood brain barrier.

PMID- 30093952
TI  - Use of expanded deltopectoral skin flaps for facial reconstruction after sizeable
      benign tumor resections.
AB  - The overall unsightliness of expansive benign facial tumors imposes both physical
      and mental suffering. Although excision is generally the optimal recourse in such
      instances, reconstructing the subsequent surgical defects is always a critical
      issue. Herein, we have described our experiences using expanded deltopectoral
      skin flaps to manage large facial wounds after excising benign tumors. Our
      endeavor called for retrospective review of 22 patients presenting between July
      2007 and March 2017 with various facial growths, including hemangiomas, nevi, and
      neurofibromas. Depending upon areas of facial involvement, unilateral or
      bilateral deltopectoral skin flaps were expanded. The stepwise process was as
      follows: expander implantation, flap transfer, pedicle delay, and eventual
      separation. Ultimately, all 22 patients undergoing this procedure expressed
      satisfaction with the results in terms of skin texture, color, and flexibility.
      This particular method may thus be a reasonable choice for repairing sizeable
      defects in the wake of benign facial tumor excisions.

PMID- 30093951
TI  - Emerging role of C5a/C5aR IL-17A axis in cGVHD.
AB  - Chronic graft-versus-host disease (cGVHD) manifests with features characteristic
      of autoimmune disease with organs attacked by pathogenic Th17 cells. However, the
      mechanism of Th17 cells generation in the setting of cGVHD is still unclear. Here
      we defined C5a/C5aR-IL-17Aaxis as a novel signaling that required in the
      pathologies of cGVHD. We firstly found a positive link between complement
      activation and the Th17 cells in patients with cGVHD. C5a, a critical component
      of complements, promoted the generation of Th17 cells in vitro and inhibition of
      the receptor for C5a (C5aR) reduced the Th17-bias response. Of note, C5aR
      blockade by PMX53 could suppress the generation of IL-17A-expressing Th17 cells
      and retard the onset and progression of cGVHD in vivo. Overall, our results
      provide new mechanistic insights that activation of C5a-C5aR signaling was
      required for IL-17A-induced immune responses in cGVHD and define novel molecular
      targets for developing effective therapeutics for cGVHD.

PMID- 30093954
TI  - Clinical efficacy of ticagrelor in patients undergoing emergency intervention for
      acute myocardial infarction and its impact on platelet aggregation rate.
AB  - OBJECTIVE: This study aims to investigate the clinical efficacy of ticagrelor in
      patients who underwent emergency percutaneous coronary intervention (PCI) for
      acute myocardial infarction (AMI), and its impact on platelet aggregation rate.
      METHODS: A total of 257 AMI patients who underwent emergency PCI in our hospital
      were included in the present study. These patients were randomly divided into two
      groups: ticagrelor group (n = 129), patients took 180 mg of ticagrelor (qd)
      before the intervention, and subsequently took 90 mg of ticagrelor (bid) for
      maintenance; clopidogrel group (n = 128), patients took 300 mg of clopidogrel
      (qd) before PCI, and subsequently took 75 mg of clopidogrel (qd) for maintenance.
      Patients in both groups took 100 mg of aspirin. The major adverse cardiovascular
      events (MACE) within one year, changes in LVEF and LVEDD, platelet aggregation
      rate and drug safety before PCI and at one week and 30 days after PCI were
      observed in these two groups. RESULTS: The differences in baseline data between
      these two groups were not statistically significant. Within one year after the
      intervention, in the ticagrelor group, the total incidence of MACE was lower (P <
      0.05), LVEF and LVEDD was improved (P < 0.05), and the decrease in platelet
      aggregation rate after the intervention was more significant (P < 0.05).
      Furthermore, the incidence of bleeding events was higher in the ticagrelor group
      than in the clopidogrel group (P < 0.05). CONCLUSIONS: Compared with clopidogrel,
      ticagrelor decreases the incidence of adverse cardiovascular events in AMI
      patients who underwent emergency PCI, does better in improving the fluctuation
      level of LVEF and LVEDD, and strongly inhibits platelet aggregation. Some
      patients encountered adverse drug events, but drug withdrawal or medication
      change did not occur.

PMID- 30093953
TI  - Assessing the impact of cigarette smoking on beta-cell function and risk for type
      2 diabetes in a non-diabetic Chinese cohort.
AB  - Although the impact of cigarette smoking on glucose homeostasis has been
      extensively studied, the results, however, are still not conclusive. We,
      therefore, conducted a cross-sectional analysis of a non-diabetic Chinese cohort
      collected by the China Health and Nutrition Survey (CHNS 2009) to comprehensively
      assess the relationship between smoking, Hemoglobin A1c, beta-cell function and
      insulin sensitivity. The cohort included a total of 5965 individuals (47.4% male)
      with a mean age of 49.23 years, and 4140 of which were non-smokers (69.4%), 834
      were current light smokers (13.9%) and 991 were current heavy smokers (16.6%).
      Current smokers were predominantly males (93.6%) with a lower BMI (22.95 versus
      23.42 kg/m2). HbA1c levels were dose-dependently increased with smoking exposure
      (5.39%, 5.42% and 5.45%, respectively, P = 0.007). Non-smokers were served as a
      referent, the adjusted ORs for type 2 diabetes were 1.12 (P = 0.256, light
      smokers) and 1.26 (P = 0.014, heavy smokers), indicating a positive relationship
      between cigarette smoking and incidence of diabetes. HOMA%B was decreased in a
      dose-responsive manner with cigarette smoking (4.80, 4.79 and 4.76, P = 0.036),
      suggesting an adverse effect of smoking on beta-cell function. Collectively,
      cigarette smoking is dose-dependently associated with decreased HOMA%B, and
      current smokers were clearly in a higher risk for diabetes as manifested by the
      elevated HbA1c.

PMID- 30093955
TI  - Evaluation of the safety and tolerability of tamoxifen for ischemia-incited renal
      injury in mice.
AB  - Tamoxifen is used to activate tamoxifen-dependent Cre recombinase (CreER) to
      generate time- and tissue-specific genetically mutant mice. However, tamoxifen is
      also an active estrogen analogue that binds with higher affinity to estrogen
      receptors and exhibits anti-apoptosis, anti-inflammation, and antifibrotic
      properties. Renal ischemia reperfusion (I/R) injury is characterized by increased
      apoptosis and inflammation, so optimal utility of tamoxifen-inducible CreER
      genetic systems in I/R model is important. The purpose of this study was to
      optimize the tamoxifen dose and evaluate its safety and tolerability in the
      development of mouse I/R injury. Seven-week-old C57/B6 mice were subjected to
      moderate reversible unilateral I/R and then injected intraperitoneally daily for
      5 days with tamoxifen at doses of 50, 100, or 200 mg/kg/day. Regardless of the
      time of sacrifice, at 5 day or 28 day after I/R injury, there were no differences
      in pathological damage, apoptosis, inflammation, or the extent of fibrosis
      between untreated and treated mice from the time point of acute kidney injury
      (AKI) to subsequently chronic kidney disease. Data above indicated that tamoxifen
      with a dose among 0 to 200 mg/kg/day was safe and tolerable for mice, without
      influencing I/R induced kidney injury in mice. The results suggest that tamoxifen
      inducible CreER genetic systems can be safely used in the mouse I/R model.

PMID- 30093956
TI  - Vincamine prevents lipopolysaccharide induced inflammation and oxidative stress
      via thioredoxin reductase activation in human corneal epithelial cells.
AB  - Lipopolysaccharide (LPS) induced keratitis is a progressive infectious ocular
      disease in which innate inflammatory responses often cause clinical tissue damage
      and vision loss. In this study, the potential protective effects of vincamine, a
      plant alkaloid used clinically as a peripheral vasodilator, against LPS induced
      inflammation and oxidative stress were investigated on human corneal epithelial
      cells (HCECs). HCECs were treated with LPS and vincamine at various
      concentrations. Cell viability, reactive oxygen species (ROS) levels, and the
      gene expression levels of interleukin-6 (IL-6), IL-8, IL-1beta, TNF-alpha,
      transforming growth factor-beta (TGF-beta) in HCECs, were assessed. The
      antioxidant potential of vincamine was evaluated by measuring the levels of
      malondialdehyde (MDA), total antioxidant capacity (T-AOC), and superoxide
      dismutase (SOD). The effects of vincamine on intracellular activities of
      thioredoxin reductase (TrxR) as well as other anti-oxidant proteins were also
      investigated in LPS treated HCECs. The results showed that vincamine protected
      HCECs from LPS induced cell viability reduction and ameliorated the inflammation.
      Vincamine exhibited a strong antioxidant activity, decreasing ROS levels and
      regulating the levels of SOD, T-AOC and MDA. Vincamine also exerted anti
      inflammatory activities by decreasing IL-6, IL-8, IL-1beta, TNF-alpha, TGF-beta
      expression. Intracellular TrxR activity was significantly activated by vincamine.
      These findings suggest that vincamine exerts positive effects against LPS induced
      oxidative stress and inflammation and may be useful in protecting corneal
      epithelial cells from LPS induced keratitis.

PMID- 30093957
TI  - A novel probe for measuring tissue bioelectrical impedance to enhance pedicle
      screw placement in spinal surgery.
AB  - Posterior spinal reconstruction with rods and pedicle screws has been widely used
      to corrects coliosis and other forms of degenerative spinal deformities. However,
      insertion of pedicle screwsis often clinically challenging, particularlyin
      patients with severe deformity. Bioelectrical impedance analysis is a technique
      that exploits the electrical properties of biological organs and tissues to
      indicate their compositions. Bioelectrical impedance measurement is non-invasive,
      simple, with adequate repeatability, and at a relatively low cost. In our study,
      we designed a bioelectrical impedance pedicle probe and use it to determine the
      bioelectrical impedance values in vitro and in vivo of different tissues relevant
      to pedicle screw insertion. We measured the bioelectrical impedance of different
      tissues relevant to pedicle screw placement in vitro and in vivo and explored the
      use of a prototype bioelectrical impedance pedicle probein guiding pedicle screw
      placement during spine surgery in animals. These data suggested that this novel
      bioelectrical impedance pedicle probe may be a new technique that has potential
      to offer accurate and safe placement of pedicle screws in spine surgery.

PMID- 30093959
TI  - Erratum: Protease activated receptor 2 in diabetic nephropathy: a double edged
      sword.
AB  - [This corrects the article on p. 4512 in vol. 9, PMID: 29118913.].

PMID- 30093958
TI  - Research progress of the relationship between pyroptosis and disease.
AB  - Pyroptosis, characterized by proinflammation, has been defined as a new type of
      programmed cell death in recent years. Inflammasomes are activated by the
      corresponding pathogen-associated molecular patterns (PAMPS) or damage-associated
      molecular patterns (DAMPS), followed up by the cleavage of pro-interleukin-1beta
      (pro-IL-1beta), pro-interleukin-18 (pro-IL-18) and gasdermin D. The N-terminal
      fragment of gasdermin D gives rise to the destruction of cell membrane, leading
      to cell rupture as well as the efflux of proinflammatory cytokines. Recent
      studies have shown that pyroptosis is associated with a variety of diseases due
      to its proinflammation effect and the dysfunction of related cells. The
      relationship between pyroptosis and associated diseases is described in this
      review.

PMID- 30093960
TI  - Erratum: Exogenous glutathione contributes to cisplatin resistance in lung cancer
      A549 cells.
AB  - [This corrects the article on p. 1295 in vol. 10, PMID: 29887946.].

PMID- 30093961
TI  - USING DEEP NEURAL NETWORKS FOR RADIOGENOMIC ANALYSIS.
AB  - Radiogenomic studies have suggested that biological heterogeneity of tumors is
      reflected radiographically through visible features on magnetic resonance (MR)
      images. We apply deep learning techniques to map between tumor gene expression
      profiles and tumor morphology in pre-operative MR studies of glioblastoma
      patients. A deep autoencoder was trained on 528 patients, each with 12,042 gene
      expressions. Then, the autoencoder's weights were used to initialize a supervised
      deep neural network. The supervised model was trained using a subset of 109
      patients with both gene and MR data. For each patient, 20 morphological image
      features were extracted from contrast-enhancing and peritumoral edema regions. We
      found that neural network pre-trained with an autoencoder and dropout had lower
      errors than linear regression in predicting tumor morphology features by an
      average of 16.98% mean absolute percent error and 0.0114 mean absolute error,
      where several features were significantly different (adjusted p-value < 0.05).
      These results indicate neural networks, which can incorporate nonlinear,
      hierarchical relationships between gene expressions, may have the
      representational power to find more predictive radiogenomic associations than
      pairwise or linear methods.

PMID- 30093962
TI  - The recent landscape of cancer research worldwide: a bibliometric and network
      analysis.
AB  - The aim of this paper is to map the scientific landscape related to cancer
      research worldwide between 2012 and 2017. We use scientific publication data from
      Web of Science Core Collection and combine bibliometrics and social network
      analysis techniques to identify the most relevant journals, research areas,
      countries and research organizations in cancer scientific landscape. The results
      show: Oncotarget as the journal with most publications; a significant increase in
      China's publications, reaching United States' publications in 2017; MD Cancer
      Center, University of California and Harvard University as organizations with
      most publications; cell biology as the most frequent research area; breast, lung
      and colorectal cancer as the most frequent keywords; high density of co
      authorship between organizations in the West, especially in the US, and low
      density between organizations in Asian and lower and medium income countries. Our
      findings can be used to guide a global knowledge platform guiding policy,
      planning and funding decisions as well as to establish new institutional
      collaborations.

PMID- 30093963
TI  - MicroRNA profiling and their pathways in South African individuals with
      prediabetes and newly diagnosed type 2 diabetes mellitus.
AB  - Early identification of individuals with elevated risk of developing diabetes
      mellitus, followed by the implementation of effective prevention interventions
      can delay the onset of the disease and related complications. In this regard,
      recent studies have shown that miRNAs are useful as early markers of certain
      disease types, including diabetes. We used high throughput sequencing to assess
      miRNA expression profiles from whole blood of 12 individuals with screen-detected
      diabetes, 12 with prediabetes and 12 with normal glucose tolerance, matched for
      age, blood pressure, smoking and body mass index. We identified a total of 261
      (57 novel) differentially expressed miRNA profiles between the study groups.
      Comparison of the miRNA expression profiles between prediabetess and diabetes
      revealed 25 common miRNA, but highlighted some interesting differences. For
      instance, three miRNAs (miR-126-3p, miR-28-3p miR-486-5p) were dysregulated in
      prediabetes compared to screen-detected diabetes. Target gene analysis showed
      thousands of potential genes and KEGG pathway analysis revealed 107 significant
      pathways of which some are involved signal transduction, cell-cell
      communications, cell growth and death, immune response, endocrine system and
      metabolic diseases. This first detailed African study has shown both known and
      novel differentially expressed miRNAs in relation to glucose tolerance.

PMID- 30093964
TI  - Targeted next generation sequencing identified a high frequency genetic mutated
      profile in wood smoke exposure-related lung adenocarcinoma patients.
AB  - Background: Wood smoke exposure (WSE) has been associated with an increased risk
      of lung cancer development. WSE has been related with high frequency of EGFR
      mutations and low frequency of KRAS mutations. The aim of this study was to
      evaluate large scale genomic alterations in lung adenocarcinomas associated with
      WSE using targeted next generation sequencing. Methods: DNA multi-targeted
      sequencing was performed in 42 fresh-frozen samples of advanced lung
      adenocarcinomas. The TruSeQ Cancer Panel (Illumina) was used for genomic library
      construction and sequencing assays. Results: WSE rate was higher in women
      (p=0.037) and non-smokers (p=0.001). WSE correlated with mutations in the genes
      SMARCB1 (p=0.002), Ataxia telangiectasia mutated (p=0.004), Kinase Insert Domain
      Receptor (p=0.006), and were borderline significant in RET and EGFR exon. Genomic
      alterations significantly co-occurred in the tumor suppressor gene ATM with the
      following genes: SMARCB1, EGFR exon 7, RET and KDR. Clinical factors associated
      with poor prognosis were ECOG >= 2 (p= 0.014), mutations in KDR (p= 0.004) and
      APC genes (p < 0.001). Conclusions: Lung adenocarcinoma patients with WSE showed
      a distinctive mutated profile for the SMARCB1, ATM, EGFR exon 7, RET and KDR
      genes. ECOG status and KDR gene mutations were significantly associated with poor
      prognosis.

PMID- 30093966
TI  - Preclinical, non-genetic models of lung adenocarcinoma: a comparative survey.
AB  - Lung cancer is the leading cause of cancer-related mortality worldwide. Animal
      models are key in analyzing cancer biology and therapy evaluation. We here
      compared relevant non-genetic lung cancer models with regard to tumor induction
      period, incidence, morbidity and mortality rate and the immunological composition
      of primary tumors and the occurrence of tertiary lymphoid organs (TLO): (I)
      intraperitoneal Urethane injection (1g/kg), (II) Lewis lung carcinoma (LLC) cell
      line model (intravenous or subcutaneous), and (III) ex vivo three-dimensional
      (3D) primary cell culture model established from subcutaneously developed LLC
      induced tumors. The incidence of Urethane induced lung tumors was 100% in both,
      C57BL/6 and BALB/c strains without morbidity or mortality at twenty weeks after
      injection. The mean size of tumor nodules after Urethane injection was
      significantly larger in BALB/c mice vs. C57BL/6 (p<0.01). Three times of Urethane
      injection produced significantly more tumor nodules in both mouse strains
      compared to one injection (BALB/c: p<0.01; C57BL/6: p<0.05). TLOs were only found
      in the Urethane-induced model. Although the cell line models also showed 100%
      induction rate, morbidity was high due to skin ulceration on the inoculation site
      and the development of pleural effusions in the subcutaneous model and the
      intravenous model, respectively. Tendencies, but no significant differences
      (p>0.05) could be found in the count of CD4+, CD8+, F4/80+ and NKp46+ cells in a
      tumor nodule among investigated models. All discussed models provided a high
      tumor incidence rate. TLOs were exclusively found in the Urethane-induced model.
      No significant difference could be found regarding immune cells across models.

PMID- 30093965
TI  - APOBEC3B gene expression as a novel predictive factor for pathological complete
      response to neoadjuvant chemotherapy in breast cancer.
AB  - Background: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B
      (APOBEC3B) is a gene editing enzyme with cytidine deaminase activity and high
      expression of its mRNA in breast tumors have been shown to be associated with
      progressive cases and poor prognosis. In this study, we aimed to examine the
      relationship between the expression of APOBEC3B and the effect of neoadjuvant
      chemotherapy (NAC) using pretreatment biopsy tissue, and examined whether the
      expression of APOBEC3B influenced chemotherapy efficacy. Methods: We
      retrospectively selected a total of 274 patients with primary breast cancer who
      received NAC in more than 4 courses and underwent surgery at our institute. We
      assessed the expression of APOBEC3B mRNA using pretreatment biopsy specimens of
      NAC by quantitative real-time PCR (qRT-PCR) and examined the relationship between
      APOBEC3B mRNA expression and sensitivity to chemotherapy using pathological
      complete response (pCR) as an indicator. Further, we assessed the prognostic
      value of APOBEC3B in the patients receiving NAC. Results: APOBEC3B mRNA
      expression levels were successfully assessed in 173 (63.1%) of the 274 specimens.
      The total pCR rate was 36.4% (n = 63). An association between APOBEC3B expression
      levels and pCR was observed (Wilcoxon test, P <= 0.0001). The patients were
      divided into two groups, low (n = 66) and high (n = 107), according to the
      APOBEC3B expression levels, using the cut-off value calculated by the receiver
      operating characteristics (ROC) curve for pCR. The rate of pCR was significantly
      higher among the patients in the high group than among those in the low group
      (47.7% vs 18.2%, P <= 0.0001). High APOBEC3B expression was significantly
      associated with high nuclear grade (P = 0.0078), high Ki-67 labeling index (P =
      0.0087), estrogen receptor (ER) negativity (P <= 0.0001) and human epidermal
      growth factor receptor 2 (HER2) negativity (P = 0.032). Tumor size (P = 0.011),
      ER (P <= 0.0001), HER2 (P = 0.0013) and APOBEC3B expression (P = 0.037) were
      independent predictive factors for pCR in multivariate analysis. However, there
      was no association between APOBEC3B expression and prognosis. Conclusions: Our
      study showed that APOBEC3B mRNA expression correlated with sensitivity to NAC in
      breast cancer patients. In contrast to previous studies, APOBEC3B mRNA expression
      was not associated with breast cancer prognosis in patients receiving NAC.

PMID- 30093968
TI  - The prognostic significance of high/positive expression of tissue VEGF in ovarian
      cancer.
AB  - Background & aim: At present, numerous reports have shown that high/positive
      expression of tissue vascular endothelial growth factor (VEGF) may be associated
      with the prognosis of patients with ovarian cancer. However, their results still
      remained controversy. Thus, this meta-analysis was designed to analyze and assess
      the prognostic value of tissue VEGF expression in patients with ovarian cancer.
      Method: We searched PubMed, Embase, Cochrane Library and Web of Science to
      October, 2017. Hazard Ratio (HR) with its 95% confidence intervals (CIs) was used
      to evaluate the association between high/positive expression of tissue VEGF and
      the prognosis of ovarian cancer patients. All statistical analyses were performed
      using standard statistical procedures provided in RevMan 5.2. Result: A total of
      18 studies (including 1145 patients) were included for this meta-analysis. The
      positive/high expression of tissue VEGF had an obvious association with overall
      survival (OS) (HR 2.24, 95% CI 1.36-3.70; P=0.002), progression-free survival
      (PFS) (HR 1.60, 95% CI 1.11-2.31; P=0.01) and disease-free survival (DFS) (HR
      3.49, 95% CI 1.27-9.56; P=0.02) of patients with ovarian cancer respectively.
      Conclusion: The present meta-analysis indicated that positive/high expression of
      tissue VEGF may have a close association with survival of ovarian cancer.

PMID- 30093967
TI  - A diagnostic autoantibody signature for primary cutaneous melanoma.
AB  - Melanoma is an aggressive form of skin cancer that is curable by surgical
      excision in the majority of cases, if detected at an early stage. To improve
      early stage melanoma detection, the development of a highly sensitive diagnostic
      test is of utmost importance. Here we aimed to identify antibodies to a panel of
      tumour associated antigens that can differentiate primary melanoma patients and
      healthy individuals. A total of 245 sera from primary melanoma patients and
      healthy volunteers were screened against a high-throughput microarray platform
      containing 1627 functional proteins. Following rigorous statistical analysis, we
      identified a combination of 10 autoantibody biomarkers that, as a panel, displays
      a sensitivity of 79%, specificity of 84% and an AUC of 0.828 for primary melanoma
      detection. This melanoma autoantibody signature may prove valuable for the
      development of a diagnostic blood test for routine population screening that,
      when used in conjunction with current melanoma diagnostic techniques, could
      improve the early diagnosis of this malignancy and ultimately decrease the
      mortality rate of patients.

PMID- 30093969
TI  - Colorectal tumor prevention by the progestin medroxyprogesterone acetate is
      critically dependent on postmenopausal status.
AB  - The large randomized placebo controlled trials of the Women's Health Initiative
      have shown that the combination of estrogen and progestin medroxyprogesterone
      acetate (MPA) protects from colorectal cancer in postmenopausal women. No effect
      was observed in women treated with estrogen alone. This suggests that
      progesterone, or more specifically the progestin MPA may have chemopreventive
      activity. The effect of MPA on colorectal carcinogenesis has been difficult to
      study in animal models. Most models are not affected by either depleting female
      hormones by ovariectomy or treatment with MPA. Importantly, an ovariectomy fails
      to reproduce one of the hall marks of the postmenopausal state in women with
      intact ovaries. That is, the continued production of androgens by the atrophic
      postmenopausal ovaries. Here we show that adenoma incidence is increased in the
      vinyl cylcohexene diepoxide (VCD) mouse model of the menopause compared to age
      matched fertile female mice. Treatment with MPA protected VCD treated mice from
      adenomagenesis, but had no effect on adenoma numbers in age-matched fertile
      female mice. Our data show that the protective effect of MPA depends on the
      postmenopausal state and suggest that MPA monotherapy may be studied as a
      chemopreventive agent in postmenopausal women.

PMID- 30093971
TI  - Detection of identical T cell clones in peritumoral pleural effusion and
      pneumonitis lesions in a cancer patient during immune-checkpoint blockade.
AB  - Although immune-related adverse events (irAEs) of treatment with immune
      checkpoint inhibitors may be due to cellular immunity mediated by T lymphocytes,
      their pathogenesis has remained unknown. Here we collected bronchoalveolar lavage
      fluid (BALF) from a cancer patient with nivolumab-induced pneumonitis and
      isolated mononuclear cells for next-generation sequencing of the complementarity
      determining region of the T cell receptor (TCR) beta chain. Mononuclear cells in
      peritumoral pleural effusion isolated from the patient were similarly analyzed,
      and the results obtained for the two specimens were compared. A substantial
      number of TCRbeta clones in BALF were also identified among lymphocytes in the
      peritumoral pleural effusion. Such a correlation was not apparent between TCRbeta
      clones in BALF and those in peripheral blood. Moreover, many tumor-associated
      clones with a read frequency of >=0.10% were also present in BALF. Our data
      suggest that irAEs might be induced by drug-activated lymphocytes originating
      from tumor tissue. Deep sequencing will thus be indispensable for investigations
      of the immune-based pathogenesis of, and the development of optimal treatments
      for, irAEs.

PMID- 30093970
TI  - A k-mer based transcriptomics approach for antisense drug discovery targeting the
      Ewing's family of tumors.
AB  - Ewing's sarcoma treatment failures are associated with high mortality indicating
      a need for new therapeutic approaches. We used a k-mer counting approach to
      identify cancer-specific mRNA transcripts in 3 Ewing's Family Tumor (EFT) cell
      lines not found in the normal human transcriptome. Phosphorodiamidate morpholino
      oligomers targeting six EFT-specific transcripts were evaluated for cytotoxicity
      in TC-32 and CHLA-10 EFT lines and in HEK293 renal epithelial control cells.
      Average morpholino efficacy (EC50) was 0.66 +/- 0.13 in TC-32, 0.25 +/- 0.14 in
      CHLA-10 and 3.07 +/- 5.02 uM in HEK293 control cells (ANOVA p < 0.01). Synergy
      was observed for a cocktail of 12 morpholinos at low dose (0.3 uM) in TC-32
      cells, but not in CHLA-10 cells. Paired synergy was also observed in both EFT
      cell lines when the PHGDH pre-mRNA transcript was targeted in combination with
      XAGE1B or CYP4F22 transcripts. Antagonism was observed when CCND1 was targeted
      with XAGE1B or CYP4F22, or when IGFBP-2 was targeted with CCND1 or RBM11. This
      transcriptome profiling approach is highly effective for cancer drug discovery,
      as it identified new EWS-specific target genes (e.g. CYP4F22, RBM11 and IGBP-2),
      and predicted effective antisense agents (EC50 < 1 uM) that demonstrate both
      synergy and antagonism in combination therapy.

PMID- 30093972
TI  - Positive crosstalk between EGFR and the TF-PAR2 pathway mediates resistance to
      cisplatin and poor survival in cervical cancer.
AB  - Cisplatin-based chemoradiation is the standard treatment for cervical cancer, but
      chemosensitizing strategies are needed to improve patient survival. EGFR
      (Epidermal Growth Factor Receptor) is an oncogene overexpressed in cervical
      cancer that is involved in chemoresistance. Recent studies showed that EGFR
      upregulates multiple elements of the coagulation cascade, including tissue factor
      (TF) and the protease-activated receptors (PAR) 1 and 2. Moreover, many G protein
      coupled receptors, including PARs, have been implicated in EGFR transactivation.
      However, the role of coagulation proteins in the progression of cervical cancer
      has been poorly investigated. Herein we employed cervical cancer cell lines and
      The Cancer Genome Atlas (TCGA) database to evaluate the role of EGFR, TF and PAR2
      in chemoresistance. The SLIGKL-NH2 peptide (PAR2-AP) and coagulation factor VIIa
      (FVIIa) were used as PAR2 agonists, while cetuximab was used to inhibit EGFR. The
      more aggressive cell line CASKI showed higher expression levels of EGFR, TF and
      PAR2 than that of C33A. PAR2 transactivated EGFR, which further upregulated
      cyclooxygenase-2 (COX2) expression. PAR2-AP decreased cisplatin-induced apoptosis
      through an EGFR- and COX2-dependent mechanism. Furthermore, treatment of CASKI
      cells with EGF upregulated TF expression, while treatment with cetuximab
      decreased the TF protein levels. The RNA-seq data from 309 TCGA samples showed a
      strong positive correlation between EGFR and TF expression (P = 0.0003). In
      addition, the increased expression of EGFR, PAR2 or COX2 in cervical cancer
      patients was significantly correlated with poor overall survival. Taken together,
      our results suggest that EGFR and COX2 are effectors of the TF/FVIIa/PAR2
      signaling pathway, promoting chemoresistance.

PMID- 30093973
TI  - Serum N-glycome alterations in colorectal cancer associate with survival.
AB  - Proteins are routinely measured in clinical laboratories for diagnosis, prognosis
      and therapy monitoring. Nevertheless, both test improvements (performance) and
      innovations (biomarkers) are needed, and protein N-glycosylation offers a rich
      source of potential markers. Here, we have analyzed the total serum N-glycome in
      a matched case-control study (124 cases versus 124 controls) of colorectal cancer
      patients. The results were validated in an independent sample cohort (both 61
      cases versus 61 controls) and further tested in post-operative samples of cured
      patients. Our results revealed significant differences between patients and
      controls, with increased size (antennae) and sialylation of the N-glycans in the
      colorectal cancer patient sera as compared to mainly di-antennary N-glycans in
      sera from controls. Furthermore, glycan alterations showed strong associations
      with cancer stage and survival: The five-year survival rate largely varied
      between patients with an altered serum N-glycome (46%) and an N-glycome similar
      to controls (87%). Importantly, the total serum N-glycome showed prognostic value
      beyond age and stage. This clinical glycomics study provides novel serum
      biomarker candidates and shows the potential of total serum N-glycans as a
      prognostic panel. Moreover, serum N-glycome changes reverted to a control-like
      profile after successful treatment as was demonstrated from pre- and post
      operative samples.

PMID- 30093974
TI  - The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling
      protein (KMT2C), in osteosarcoma.
AB  - Osteosarcoma is the most common paediatric primary non-hematopoietic bone tumor;
      the survival is related to the response to chemotherapy and development of
      metastases. KMT2C is a chromatin-modifying and remodelling protein and its
      expression has never been studied in osteosarcoma. The aim of this study was to
      understand the role of KMT2C in the osteosarcoma carcinogenesis and metastatic
      progression to identify a new molecular target and to provide new therapeutic
      approach. We performed the immunohistochemical and gene expression analysis of
      KMT2C in 32 samples of patients with diagnosis of osteosarcoma with known clinic
      pathological data and we analysed the expression of genes involved in the
      metastatic pathway in four osteosarcoma cell lines by blocking the KMT2C
      expression using siRNA. We found a nuclear-cytoplamic trafficking of KMT2C and
      the cytoplasmic localization was higher than the nuclear localization (p <
      0.0001). Moreover, the percentage of cells with cytoplasmic positivity increased
      from low grade primary tissue to metastatic tissues. The cytoplasmic localization
      of KMT2C could lead to a change in its function supporting osteosarcoma
      carcinogenesis and progression. Our hypothesis is that KMT2C could affect the
      enhancer activity of genes influencing the invasive properties and metastatic
      potential of osteosarcoma.

PMID- 30093975
TI  - Extracellular ATP is a danger signal activating P2X7 receptor in a LPS mediated
      inflammation (ARDS/ALI).
AB  - Acute respiratory distress syndrome (ARDS) is a life-threating lung condition
      resulting from a direct and indirect injury to the lungs [1, 2].
      Pathophysiologically it is characterized by an acute alveolar damage, an
      increased permeability of the microvascular-barrier, leading to protein-rich
      pulmonary edema and subsequent impairment of arterial oxygenation and respiratory
      failure [1]. This study examined the role of extracellular ATP in recruiting
      inflammatory cells to the lung after induction of acute lung injury with
      lipopolysaccharide (LPS). However, the precise mechanism is poorly understood.
      Our objective was to investigate the functional role of the P2X7 receptor in the
      pathogenesis of acute respiratory distress syndrome (ARDS/ acute lung injury
      (ALI)) in vitro and in vivo. We show that intratracheally applied LPS causes an
      acute accumulation of ATP in the BALF (bronchoalveolar lavage) and lungs of mice.
      Prophylactic and therapeutic inhibition of P2X7R signalling by a specific
      antagonist and knock-out experiments was able to ameliorate the inflammatory
      response demonstrated by reduced ATP-levels, number of neutrophils and
      concentration of pro-inflammatory cytokine levels in the BALF. Experiments with
      chimeric mice showed that P2X7R expression on immune cells was responsible for
      the observed effect. Consistently, the inflammatory response is diminished only
      by a cell-type specific knockdown of P2X7 receptor on non-stationary immune
      cells. Since the results of BALF from patients with acute ARDS or pneumonia
      simulated the in vivo data after LPS exposure, the P2X7 receptor may be a new
      therapeutic target for treatment in acute respiratory distress syndrome
      (ARDS/ALI).

PMID- 30093976
TI  - Clinical genetic testing outcome with multi-gene panel in Asian patients with
      multiple primary cancers.
AB  - Background: Developing multiple cancers is an indicator of underlying hereditary
      cancer predisposition, but there is a paucity of data regarding the clinical
      genetic testing outcomes of these patients. Methods: We compared cancer index
      patients with >=2 primary malignancies versus 1 primary cancer who underwent
      clinical evaluation and testing with multi-gene panels comprising up to 49 genes
      from 1998-2016. Results: Among 1191 cancer index patients, 80.6%, 17.2%, and 2.2%
      respectively had 1, 2, and >=3 primary malignancies. For patients with 2 primary
      cancers (n=205), the most common cancer pairs were bilateral breast (37.5%),
      breast-ovary (11.7%), endometrium-ovary (9.2%), colon-endometrium (3.9%) and
      colon-colon (3.4%). 42.3% patients underwent gene testing including 110/231
      (47.6%) with multiple malignancies. Pathogenic variants were found more
      frequently in younger patients, in those with a family history of cancer related
      to the suspected syndrome, and a trend towards significance in those with
      multiple primary cancers (35.5% vs. 25.6%, p = 0.09). In patients with multiple
      cancers, pathogenic variants were most commonly identified in BRCA1 (38.5%),
      BRCA2 (17.9%), and the mismatch repair genes (20.5%), while 23.1% of pathogenic
      mutations were in other moderate- to high-penetrance cancer predisposition genes
      including APC, ATM, MUTYH, PALB2, RAD50 and TP53. Conclusion: Patients with
      multiple cancers were more likely to carry pathogenic mutations than those with
      single cancer. About three-quarters of deleterious mutations in patients with
      multiple primary cancers were in BRCA1/2 and the mismatch repair genes, but multi
      gene panel testing facilitated the detection of mutations in another 6 genes and
      is warranted in this high-risk population.

PMID- 30093977
TI  - SIRT1-dependent epigenetic regulation of H3 and H4 histone acetylation in human
      breast cancer.
AB  - Breast cancer is the most frequently diagnosed malignancy in women worldwide. It
      is well established that the complexity of carcinogenesis involves profound
      epigenetic deregulations that contribute to the tumorigenesis process.
      Deregulated H3 and H4 acetylated histone marks are amongst those alterations.
      Sirtuin-1 (SIRT1) is a class-III histone deacetylase deeply involved in
      apoptosis, genomic stability, gene expression regulation and breast
      tumorigenesis. However, the underlying molecular mechanism by which SIRT1
      regulates H3 and H4 acetylated marks, and consequently cancer-related gene
      expression in breast cancer, remains uncharacterized. In this study, we
      elucidated SIRT1 epigenetic role and analyzed the link between the latter and
      histones H3 and H4 epigenetic marks in all 5 molecular subtypes of breast cancer.
      Using a cohort of 135 human breast tumors and their matched normal tissues, as
      well as 5 human-derived cell lines, we identified H3k4ac as a new prime target of
      SIRT1 in breast cancer. We also uncovered an inverse correlation between SIRT1
      and the 3 epigenetic marks H3k4ac, H3k9ac and H4k16ac expression patterns. We
      showed that SIRT1 modulates the acetylation patterns of histones H3 and H4 in
      breast cancer. Moreover, SIRT1 regulates its H3 acetylated targets in a subtype
      specific manner. Furthermore, SIRT1 siRNA-mediated knockdown increases histone
      acetylation levels at 6 breast cancer-related gene promoters: AR, BRCA1, ERS1,
      ERS2, EZH2 and EP300. In summary, this report characterizes for the first time
      the epigenetic behavior of SIRT1 in human breast carcinoma. These novel findings
      point to a potential use of SIRT1 as an epigenetic therapeutic target in breast
      cancer.

PMID- 30093978
TI  - Is water exchange superior to water immersion in detecting adenomas during
      colonoscopies? Results from a Bayesian network meta-analysis.
AB  - Aim: Water-assisted colonoscopy (water exchange [WE] and water immersion [WI])
      has been shown to improve the adenoma detection rate. However, few studies have
      compared these two methods head-to-head. Thus, we conducted a network meta
      analysis to integrate both direct and indirect evidence comparing the
      effectiveness of these two procedures. Method: We searched PubMed, Web of
      Science, and the Cochrane Central Register of Controlled Trials for original
      papers and abstracts published up to March 2018. Randomized controlled trials
      (RCTs) reporting data in accordance with the eligibility criteria were included
      in this study. We performed a Bayesian random effects network meta-analysis with
      mixed comparisons. Results: Twenty-nine studies (n = 11464 patients) including 6
      direct and 23 indirect comparisons were included in this network meta-analysis.
      There was a statistically significant difference in the efficacy of adenoma
      detection when WE was compared with WI (risk ratio [RR]: 1.2, 95% credible
      interval [CrI]: 1.1-1.3), air insufflation (AI; RR: 1.3, 95% CrI: 1.1-1.4), and
      carbon dioxide (CO2) insufflation (RR: 1.2, 95% CrI: 1.1-1.5). The different
      methods were ranked in order from the most to least effective in adenoma
      detection as follows: WE, WI, AI, and CO2. Moreover, although there were no
      significant differences in pain scores, willingness to repeat, caecal intubation
      rate, or total procedure time between WI and WE colonoscopy, WE required a longer
      caecal intubation time than WI. Conclusion: This network meta-analysis supposes
      that WE may be superior to WI in detecting adenomas during colonoscopies without
      affecting other technical features or patient acceptance.

PMID- 30093979
TI  - Dry eye syndrome and the subsequent risk of chronic fatigue syndrome-a
      prospective population-based study in Taiwan.
AB  - Background and Aim: The clinical association between dry eye syndrome (DES) and
      chronic fatigue syndrome (CFS) remain unclear with less evidences. We aimed to
      investigate the relationship between CFS and DES using a national insurance and
      prospective cohort study. Methods: Data from the Longitudinal Health Insurance
      Database 2000 was applied to estimate the incidence of CFS among patients with
      DES, and their age- and sex-matched controls without DES over a long-term follow
      up period. All participants were CFS free at baseline, before the interval (2005
      2007), but were later diagnosed with CFS. DES patients and its relative matched
      controls were excluded prevalent CFS before the same interval. Results: We
      identified 884 patients with DES and 3,536 matched controls in baseline and
      estimated the hazard ratios for incident CFS in the follow-up period. Patients
      with DES had a 2.08-fold considerably increasing risk of developing CFS, compared
      to non-DES group. An elevated risk of developing CFS remained (1.61-fold risk)
      even after adjusting for age, sex, and comorbidities. There was a presence of
      increasing risk in DES-related CFS when CFS-related comorbidities existing
      (adjusted hazard ratio, 1.98, 95% confidence interval, 1.19-3.29; p < 0.01). The
      subsequent risk for CFS between DES and non-DES patients was significant
      increased with three or more annual medical visits, the adjusted risk for CFS was
      4.88-fold risk (95% CI, 2.26-10.58, p < 0.001). Conclusion: We recommended that
      physicians should be aware of the increased risk of CFS among DES patients and
      adequately assess the health impacts among these patients.

PMID- 30093981
TI  - Correction: Upregulation of microRNA135a-3p and death receptor 5 plays a critical
      role in Tanshinone I sensitized prostate cancer cells to TRAIL induced apoptosis.
AB  - [This corrects the article DOI: 10.18632/oncotarget.2152.].

PMID- 30093982
TI  - Clinical development of RET inhibitors in RET-rearranged non-small cell lung
      cancer: Update.
AB  - Precision oncology is now the evidence-based standard of care for the management
      of many advanced non-small cell lung cancers (NSCLC). Notably, new molecular
      profiling technologies have permitted dynamic growth in the identification of
      actionable driver oncogenes including RET rearrangements. RET oncogenes cannot be
      adequately detected by immunohistochemistry, although fluorescence in situ
      hybridization, reverse transcriptase polymerase chain reaction and next
      generation sequencing are complementary diagnostic tools. In the clinical
      setting, the benefit of the most developed RET inhibitors, i.e., cabozantinb,
      vandetanib and lenvatinb, in terms of response and median progressionfree
      survival has been demonstrated. The absence of striking clinical results of RET
      inhibitors underscores the clear need for development of more selective and
      potent RET inhibitors. This paper reviews the clinical data available on RET
      inhibitors in RET-associated NSCLC.

PMID- 30093984
TI  - Don't cancel the surgery just yet! A case report of positive preoperative
      pregnancy test due to a soft tissue sarcoma production of ectopic beta human
      chorionic gonadotropin.
AB  - Soft tissue sarcomas are a rare group of mesenchymal malignancies which can range
      from low to high grade. These tumors have different clinical, radiographic, and
      histopathological characteristics. Beta human chorionic gonadotropin is a
      naturally secreted hormone by placental syncytiotrophoblast cells during
      pregnancy. On very rare occasions, sarcomas can develop the ability to
      ectopically produce human chorionic gonadotropin. Very few cases exist in the
      literature of soft tissue sarcomas expressing this hormone. We report the case of
      a 55-year-old female who presented with a posterior thigh soft tissue sarcoma who
      on the day of surgical resection was found to have an unusually elevated serum
      human chorionic gonadotropin. Positive immunohistochemical staining of the
      resected mass confirmed the sarcoma as the source of the beta human chorionic
      gonadotropin.

PMID- 30093983
TI  - Testosterone, prolactin, and oncogenic regulation of the prostate gland. A new
      concept: Testosterone-independent malignancy is the development of prolactin
      dependent malignancy!
AB  - Hormone-independent malignancy is a major issue of morbidity and deaths that
      confronts prostate cancer. Despite decades of research, the oncogenic and
      hormonal implications in the development and progression of prostate malignancy
      remain mostly speculative. This is largely due to the absence and/or lack of
      consideration by contemporary clinicians and biomedical investigators regarding
      the established implications of the co-regulation of testosterone and prolactin
      in the development, maintenance, metabolism and functions of the prostate gland.
      Especially relevant is the major metabolic function of production of high levels
      of citrate by the peripheral zone acinar epithelial cells. Citrate production,
      along with growth and proliferation by these cells, is regulated by co-existing
      testosterone and prolactin signaling pathways; and by the oncogenic down
      regulation of ZIP1 transporter/zinc/citrate in the development of malignancy.
      These relationships had not been considered in the issues of hormonedependent
      malignancy. This review provides the relevant background that has established the
      dual role of testosterone and prolactin regulation of the prostate gland; which
      is essential to address the implications in the oncogenic development and
      progression of hormone-dependent malignancy. The oncogenic factor along with
      testosterone-dependent and prolactin-dependent relationships leads to the
      plausible concept that androgen ablation for the treatment of
      testosteronedependent malignancy results in the development of prolactindependent
      malignancy; which is testosterone-independent malignancy. Consequently, both
      testosterone ablation and prolactin ablation are required to prevent and/or abort
      terminal hormonedependent prostate cancer.

PMID- 30093986
TI  - Intraductal papillary mucinous neoplasm originating from a heterotopic pancreas
      within the jejunum: a case report.
AB  - We report a case of intraductal papillary mucinous neoplasm arising within the
      heterotopic pancreatic tissue which was found incidentally in the jejunum during
      surgery for bowel obstruction. A 54-year-old female patient was admitted to our
      hospital due to sudden abdominal pain. In preoperative findings, we diagnosed
      bowel obstruction and performed surgery. Intra-operative findings showed adhesive
      intestinal obstruction, we performed synechiotomy for adhesion release. During
      surgery, when searching the small intestine, we coincidentally found a tumor in
      the jejunum and partial resected the jejunum. Pathological examination revealed a
      1.2 cm * 1.0 cm * 1.0 cm white yellow nodule with cystic spaces. Histological
      examination demonstrated heterotopic pancreatic tissue consisting of well-formed
      lobules of pancreatic acini and cystically dilated ducts containing intraductal
      papillary neoplasm. Moreover, in immunohistochemical staining, MUC5AC was
      diffusely expressed, but not MUC1, MUC2 and MUC6.

PMID- 30093980
TI  - Programmed cell death: the battlefield between the host and alpha-herpesviruses
      and a potential avenue for cancer treatment.
AB  - Programed cell death is an antiviral mechanism by which the host limits viral
      replication and protects uninfected cells. Many viruses encode proteins resistant
      to programed cell death to escape the host immune defenses, which indicates that
      programed cell death is more favorable for the host immune defense. Alpha
      herpesviruses are pathogens that widely affect the health of humans and animals
      in different communities worldwide. Alpha-herpesviruses can induce apoptosis,
      autophagy and necroptosis through different molecular mechanisms. This review
      concisely illustrates the different pathways of apoptosis, autophagy, and
      necroptosis induced by alpha-herpesviruses. These pathways influence viral
      infection and replication and are a potential avenue for cancer treatment. This
      review will increase our understanding of the role of programed cell death in the
      host immune defense and provides new possibilities for cancer treatment.

PMID- 30093985
TI  - Maintenance of chondrocyte phenotype during expansion on PLLA microtopographies.
AB  - Articular chondrocytes are difficult to grow, as they lose their characteristic
      phenotype following expansion on standard tissue culture plates. Here, we show
      that culturing them on surfaces of poly(L-lactic acid) of well-defined
      microtopography allows expansion and maintenance of characteristic chondrogenic
      markers. We investigated the dynamics of human chondrocyte dedifferentiation on
      the different poly(L-lactic acid) microtopographies by the expression of collagen
      type I, collagen type II and aggrecan at different culture times. When seeded on
      poly(L-lactic acid), chondrocytes maintained their characteristic hyaline
      phenotype up to 7 days, which allowed to expand the initial cell population
      approximately six times without cell dedifferentiation. Maintenance of cell
      phenotype was afterwards correlated to cell adhesion on the different substrates.
      Chondrocytes adhesion occurs via the alpha5beta1 integrin on poly(L-lactic acid),
      suggesting cell-fibronectin interactions. However, alpha2beta1 integrin is mainly
      expressed on the control substrate after 1 day of culture, and the characteristic
      chondrocytic markers are lost (collagen type II expression is overcome by the
      synthesis of collagen type I). Expanding chondrocytes on poly(L-lactic acid)
      might be an effective solution to prevent dedifferentiation and improving the
      number of cells needed for autologous chondrocyte transplantation.

PMID- 30093987
TI  - Cutaneous resurfacing around a permanent tracheostoma with an internal mammary
      artery perforator flap.
AB  - When soft tissue reconstruction near a permanent tracheostoma is needed, transfer
      of a thin and pliable flap is preferable in order to avoid occlusion of the newly
      created tracheostomal opening. Although microsurgical fasciocutaneous flap
      transfer may be desirable for such reconstruction, it is not always an option due
      to lack of recipient vessels for vascular anastomosis or a patient's poor medical
      condition that would prohibit a lengthy procedure. An alternative option is the
      internal mammary artery perforator flap, which is easy to elevate, has a long arc
      of rotation, and has a reliable blood supply. Here, we report three cases of
      cutaneous resurfacing around a permanent tracheostoma with an internal mammary
      artery perforator flap.

PMID- 30093988
TI  - Thyroid paraganglioma: a case series of a rare head and neck tumor.
AB  - Thyroid paragangliomas are rare neuroendocrine tumors. We present two cases
      analyzing their clinical presentation and pathology findings. A 44-year-old woman
      presented with a 33 mm left thyroid lobe mass. A 27-year-old male presented with
      a 27-mm right thyroid lobe mass and a FNA biopsy suggesting a follicular thyroid
      tumor. Both patients underwent total thyroidectomy. Vigorous bleeding was noted
      on the first case. Histologic sections revealed encapsulated tumors, whereas
      immunochemical stains were positive for chromogranin A, synaptophysin and NSE and
      negative for thyroglobulin, calcitonin, CEA and S-100. After an 18- and 12-month
      follow-up, respectively, both patients have no signs of local recurrence or
      distant metastasis. Preoperative diagnosis of thyroid paragangliomas was never
      attained in this series. Immunohistochemistry is mandatory for proper
      differential diagnosis. For the surgeon, the operation is technically demanding
      mainly due to the increased vascularity and friability of the tumor.

PMID- 30093989
TI  - An unusual presentation of Merkel cell carcinoma: a case report.
AB  - Merkel cell carcinoma (MCC) is a rare, aggressive carcinoma that usually arises
      in sun-exposed regions. MCC is a primary neuroendocrine tumor that arises in the
      skin. This report describes an unusual case of MCC on the buttocks that was
      treated with excision, radiation and chemotherapy. Physicians should consider MCC
      as a differential diagnosis when encountering a rapidly growing, painless lesion.
      Early diagnosis and treatment may improve patient survival rates.

PMID- 30093990
TI  - Sepsis caused by acute phlegmonous gastritis based on a group A Streptococcus.
AB  - We present a case of 45-year-old male with acute phlegmonous gastritis (APG)
      based on a hemolytic group A Streptococcus. APG is a rare and often a potentially
      fatal disease, which is characterized by a severe bacterial infection of the
      gastric wall. Because APG is a rapidly progressive disease, it comes with high
      mortality rates. Patients with an early diagnosis may undergo successful
      treatment and have a survival benefit. As soon as the diagnosis of APG is
      suspected, aggressive and adequate antibiotic treatment in combination with
      surgical intervention should be considered.

PMID- 30093991
TI  - Primary dural lymphoma mimicking meningioma: a clinical and surgical case report.
AB  - INTRODUCTION: Primary central nervous system lymphoma and its subtype, primary
      dural lymphoma, are types of non-Hodgkin's lymphoma that only occur in the
      central nervous system without any dissemination. They are extremely rare cases
      of extra nodal lymphomas accounting for 1--5% of intracranial tumors. CASE
      REPORT: We present a patient diagnosed with primary dural lymphoma in right
      frontal brain region who underwent surgical resection. Histopathological analysis
      revealed diffuse B-type large cell non-Hodgkin lymphoma. Patient underwent four
      cycles of R-CHOP and intrathecal methotrexate protocol. Six months postoperative,
      no signs of newly onset infiltration were present. DISCUSSION: Primary dural
      lymphoma most likely presents with unusual radiological signs, which can easily
      be mistaken for meningioma, the main differential diagnosis. A thorough
      immunological, histopathological and clinical patients profile should be
      conducted in order to establish the certainty of diagnosis. Although there are
      few treatment options: surgery, radiotherapy or chemotherapy, there is no
      established treatment protocol.

PMID- 30093992
TI  - Pneumoperitoneum caused by tubo-ovarian abscess in an elderly patient.
AB  - Perforation of the gastrointestinal tract may present with abdominal pain and
      imaging demonstrating pneumoperitoneum. These findings usually require
      exploratory laparotomy for diagnosis and treatment. Tubo-ovarian abscess (TOA) is
      a complication of pelvic inflammatory disease presenting as an encapsulated
      inflammatory mass, but it can occasionally involve other pelvic organs. TOA is
      most commonly seen in females of reproductive age. Here we report a case of a 63
      year-old female presenting with abdominal pain, fever and vomiting. Chest x rays
      and computed tomography scan revealed pneumoperitoneum. Emergent exploratory
      laparotomy was performed, and the findings were consistent with TOA and intact
      bowel. The patient recovered well after surgery with antibiotic therapy. In
      conclusion, while pneumoperitoneum is mostly caused by perforation of the
      gastrointestinal tract, other possibilities such as gynecological complications
      should be considered.

PMID- 30093993
TI  - 'No visible lesions?'-an unusual case of Intestinal metaplasia of the bladder.
AB  - Intestinal metaplasia (IM) of the bladder is an extremely rare benign condition.
      The clinical features are similar to other bladder tumours. Its pathogenesis is
      unclear and its role as a precursor of adenocarcinoma has long been debated.
      Transurethral resection is the main form of treatment for IM. We report the case
      of a 49-year-old gentleman who presented with visible haematuria. He was
      submitted to multiple cystoscopies which showed no macroscopic irregularities.
      Radiological (CT urogram and multiparametric MRI) imaging revealed abnormalities
      within the bladder neck, suspicious of a neoplastic lesion. Following
      transurethral resection of his trigonal area, pathology demonstrated IM occurring
      on a background of cystitis glandularis. This case highlights the unusual
      difficulty in macroscopically diagnosing IM of the bladder compared to other
      neoplasms of the bladder. Therefore, in patients with persistent visible
      haematuria there should be a low threshold to perform biopsies.

PMID- 30093994
TI  - A case of extensive hepatic adenomatosis in a renal transplant patient.
AB  - Hepatic adenomatosis (HA) is a rare condition that is traditionally associated
      with oral contraceptive use, glycogen storage diseases or metabolic syndrome.
      Here we present a renal transplant recipient that was diagnosed with HA and has
      none of the traditional risk factors. We review the literature on diagnosing and
      managing HA.

PMID- 30093995
TI  - Penoscrotal swelling-an unusual occurrence in a patient with an anastomotic leak
      following ileostomy closure.
AB  - Diverting loop ileostomy is a frequently done procedure accompanying colorectal
      surgeries. Dreaded complication is anastomotic leak. Early identification of
      anastomotic leak and apt management is required for better outcomes. Most often
      leak presents with fever, abdominal pain, rigidity, fever and hemodynamic
      instability. We report a rare occurrence of penoscrotal oedema in a patient with
      anastomotic leak and spontaneously subsiding with drainage of leaked contents.

PMID- 30093996
TI  - Necrotizing fasciitis of the lower extremity caused by perforated sigmoid
      diverticulitis-a case report.
AB  - Diverticulosis of the sigmoid colon is a common condition and occurs more often
      in elderly patients. A well-known complication is infection or even perforation
      which often requires surgery. Necrotizing fasciitis as a complication of
      perforated diverticulitis is very rare. Here, we present a case of a covered
      perforated diverticulitis in an immunosuppressed patient leading to life
      threatening necrotizing fasciitis requiring extracorporeal membrane oxygenation.
      Either hematogenous or local dissemination via the inguinal canal seemed the most
      probable mechanism of leg infection leading to hip articulation.

PMID- 30093997
TI  - Conservative management of pelvic sepsis with severe shock and multiple organ
      dysfunction syndrome after rubber-band ligation of internal haemorrhoids: surgery
      is not the only option.
AB  - Rubber-band ligation (RBL) is a safe and cost-effective approach to internal
      haemorrhoids. Potential side effects include pain, bleeding, urinary retention
      and occasionally pelvic sepsis and systemic inflammatory response syndrome
      (SIRS). At-risk patients are mainly those with immunocompromising conditions.
      Although aggressive surgical debridement or diverting colostomy appear to be
      obvious options when patients' life is threatened, their superiority to
      conservative measures has not been proven. We present the case of a 58-year-old
      female patient who presented 48 h after a RBL with pelvic pain, dysuria and
      leukocytosis. Her condition deteriorated rapidly that ventilator and inotropic
      support were required for a severe SIRS for almost 10 days. Laparoscopic
      exploration and imaging showed a rectosigmoiditis, ascites and superficial rectal
      necrosis with no transmural damage requiring an emergent surgery. Conservative
      management could possibly be a valid option in post-RBL pelvic sepsis even when
      severe associated multiple organ failure is present.

PMID- 30093998
TI  - Tracheal segmental resection for tracheal cancer: comparison of cervical collar
      incision with median sternotomy and posterolateral incision.
AB  - We compare two surgical approaches for segmental tracheal resection for tracheal
      cancer: cervical collar incision with median sternotomy and right posterolateral
      incision. In case one, a 46-year-old woman presented with adenoid cystic
      carcinoma, measuring 4.5 cm longitudinally, located at the junction of the
      cervical and mediastinal trachea. Cervical collar incision with median sternotomy
      provided a good exposure of the entire trachea. Although a relatively long
      tracheal resection (5.0 cm) was required, sufficient mobilization of the entire
      trachea facilitated low-tension anastomosis. In case 2, a 39-year-old man
      presented with squamous cell carcinoma, measuring 1.8 cm longitudinally, located
      at the lower trachea 1.8 cm from the carina to the proximal side. Right
      posterolateral incision provided a good exposure of the lower trachea. Although
      the required tracheal resection was relatively short (3.0 cm), the anastomotic
      tension was high. The high anastomotic tension was likely attributed to the
      limited mobilization of the proximal trachea.

PMID- 30093999
TI  - Fulminant descending mediastinitis secondary to infectious mononucleosis.
AB  - Descending mediastinitis is a rare, life-threatening condition caused by
      contiguous spread of oropharyngeal or cervical infection into the mediastinum.
      Infectious mononucleosis generally results in a self-limited illness
      characterized by fever, pharyngitis and lymphadenopathy. We present an
      exceptional case of an 18-year-old with infectious mononucleosis complicated by
      progressive bacterial superinfection and fulminant descending mediastinitis.
      After resuscitation, broad spectrum antibiotics, critical care support and
      definitive surgical management, they made a full recovery.

PMID- 30094001
TI  - Subacute carbon monoxide poisoning presenting as vertigo and fluctuating low
      frequency hearing loss.
AB  - It is estimated that up to 25 000 UK residents are exposed to small amounts of
      carbon monoxide (CO) annually. Symptoms of chronic exposure to CO are vague and
      non-specific and include dizziness and hearing loss. We describe a case of 38
      year-old lady presenting with a 4-month history of vertigo and hearing loss.
      Initially diagnosed as Meniere's disease, the patient was investigated and
      followed up in the clinic. She reported leakage of carbon monoxide from her gas
      fire identified during a routine safety check. Her symptoms fully resolved after
      disconnecting the faulty gas fire. A rare cause of fluctuating hearing loss and
      vertigo is described, and the diagnostic challenges are discussed.

PMID- 30094000
TI  - Adenomyomatous hyperplasia of distal common bile duct: a case report and review
      of the literature.
AB  - Adenomyomatous hyperplasia (AH) is commonly found in the gallbladder and is
      considered a tumor-like inflammatory lesion arising from Rokitansky-Aschoff
      sinus. It is extremely rare in the extrahepatic bile duct and only 15 cases have
      been reported to date. We describe a 63-year-old male patient who presented with
      cholangitis, underwent an extensive diagnostic workup, and ultimately had a
      Whipple procedure. Final pathology showed a 2.0 * 1.5 * 0.5 cm3 granular lesion
      in the distal common bile duct. There was prominent biliary epithelial
      proliferation with tubular-papillary architecture and minimal nuclear atypia in
      association with chronic inflammation, stroma reaction and smooth muscle
      proliferation. AH of the extrahepatic bile duct is a benign process but often
      requires a major operation to definitively diagnose.

PMID- 30094002
TI  - Primary greater omental torsion as a cause of acute abdomen-a rare case report.
AB  - Greater omental torsion is a rare entity that can cause acute abdominal pain, may
      mimick other abdominal pathologies, and is difficult to be diagnosed
      preoperatively. We present a case of a male patient with greater omental torsion
      mimicking the symptoms of acute appendicitis. A 31-year-old male patient
      presented with right scrotal pain, initially treated by the urologists, however,
      24 h later, he presented right lower quadrant pain, with characteristics of acute
      appendicitis. After finding in ischemic inflammatory mass on McBurney incision,
      an exploratory laparotomy was performed, revealing torsion of the greater
      omentum. Torsion of the greater omentum can be a cause of acute abdomen and could
      be misdiagnosed with acute appendicitis. Preoperative diagnosis is not easy and
      resection of the affected tissue is the preferred treatment of choice.

PMID- 30094003
TI  - Acute appendicitis as the first presentation of appendiceal metastasis of gastric
      cancer-report of a rare case.
AB  - Metastatic tumors of the appendix is a rare entity, whereas only limited data
      involving metastasis arising from gastric cancer has been reported. Herein, the
      case of gastric adenocarcinoma metastasis presenting as acute appendicitis is
      reported. A 53-year-old male, with a history of subtotal gastrectomy due to
      gastric adenocarcinoma 3 years before, was referred to the Emergency Department
      with symptoms of acute appendicitis. While this condition was confirmed
      intraoperatively, histology examination and comparison with the previously
      excised gastric specimen indicated that metastasis of gastric adenocarcinoma to
      the appendix was present. Metastatic appendiceal carcinoma arising from the
      stomach is an extremely rare condition, associated with poor prognosis.
      Aggressive treatment of the solitary lesion may present favorable results.

PMID- 30094004
TI  - The Euphausia superba transcriptome database, SuperbaSE: An online, open resource
      for researchers.
AB  - Antarctic krill (Euphausia superba) is a crucial component of the Southern Ocean
      ecosystem, acting as the major link between primary production and higher trophic
      levels with an annual predator demand of up to 470 million tonnes. It also acts
      as an ecosystem engineer, affecting carbon sequestration and recycling iron and
      nitrogen, and has increasing importance as a commercial product in the
      aquaculture and health industries. Here we describe the creation of a de novo
      assembled head transcriptome for E. superba. As an example of its potential as a
      molecular resource, we relate its exploitation in identifying and characterizing
      numerous genes related to the circadian clock in E. superba, including the major
      components of the central feedback loop. We have made the transcriptome openly
      accessible for a wider audience of ecologists, molecular biologists, evolutionary
      geneticists, and others in a user-friendly format at SuperbaSE, hosted at
      http://www.krill.le.ac.uk.

PMID- 30094007
TI  - The Friday evening case of acute kidney injury: a crystal dilemma.
AB  - We report a case of acute kidney injury (AKI) induced by amoxycillin crystalluria
      suggested by massive amounts of urinary crystals of unusual morphology. This
      hypothesis was further reinforced by a particular solubility pattern when the
      urine sample was exposed to various temperatures, alkali, acids and alcohol. We
      therefore suspended amoxycillin, which produced a rapid and complete recovery of
      kidney function. Infrared spectroscopy later confirmed the amoxycillin
      composition of the crystals. Since infrared spectroscopy is not easily available,
      we propose that these solubility tests of urinary crystals be used as a first
      step investigation when amoxycillin crystalluria is suspected.

PMID- 30094005
TI  - Myroides odoratimimus urinary tract infection in an immunocompromised patient: an
      emerging multidrug-resistant micro-organism.
AB  - Background: Myroides spp. are common environmental organisms and they can be
      isolated predominantly in water, soil, food and in sewage treatment plants. In
      the last two decades, an increasing number of infections such as urinary tract
      infections and skin and soft tissue infections, caused by these microorganisms
      has been reported. Selection of appropriate antibiotic therapy to treat the
      infections caused by Myroides spp. is difficult due to the production of a
      biofilm and the organism's intrinsic resistance to many antibiotic classes. Case
      presentation: We report the case of a 69-year-old immunocompromised patient who
      presented with repeated episodes of macroscopic haematuria, from Northern Italy.A
      midstream urine sample cultured a Gram negative rod in significant amounts (> 105
      colony-forming units (cfu)/mL), which was identified as Myroides odoratimimus.
      The patient was successfully treated with trimethoprim/sulfamethoxazole after
      antibiotic susceptibility testing confirmed its activity. Conclusion: This case
      underlines the emergence of multidrug resistant Myroides spp. which are
      ubiquitous in the environment and it demands that clinicians should be more
      mindful about the role played by atypical pathogens, which may harbour or express
      multidrug resistant characteristics, in immunocompromised patients or where there
      is a failure of empiric antimicrobial therapy.

PMID- 30094006
TI  - Acute kidney injury among adult patients undergoing major surgery in a tertiary
      hospital in Nigeria.
AB  - Background: Acute kidney injury (AKI) is an underreported but major cause of
      morbidity and mortality among patients undergoing major surgical interventions in
      sub-Saharan Africa (SSA). Whereas AKI is often seen following major cardiac
      surgery in high-income countries, a similar spectrum of surgical diseases and
      interventions is not seen in developing countries. The impacts on surgical
      outcomes have also not been well characterized in SSA. This study aimed at
      identifying risk factors, incidence and determinants and short-term outcomes of
      AKI among patients undergoing major surgery. Methods: This was a cohort study of
      adult patients undergoing major surgery at the University College Hospital,
      Ibadan, Nigeria. Data obtained were sociodemographic details, risk factors for
      AKI, details of surgery, anaesthesia and intra-operative events and short-term
      outcomes. Blood samples were obtained for pre-operative (pre-op) full blood
      count, serum electrolytes, blood urea and creatinine (SCr). Post-operatively
      (Post-op) SCr was determined at 24 h, Day 7 post-op and weekly until each patient
      was discharged. Results: A total of 219 subjects who had major surgery (86.3%
      elective) were enrolled. The median age of the patients was 46 (range 18-73)
      years and 72.6% were females. The surgeries performed were mostly simple
      mastectomies (37.4%), exploratory laparotomies (22.8%) and total thyroidectomies
      (16.4%). The incidences of AKI were 18.7% at 24 h and 17.4% at Day 7 post-op,
      while cumulative AKI incidence was 22.5% at 1-week post-op. Pre-op elevated SCr
      [odds ratio (OR) 3.86], sepsis (OR 2.69), anaemia (OR 2.91) and duration of
      surgery >120 min (OR 1.75) were independently associated with AKI. In-patient
      mortality was 20.4% in individuals with AKI and 5.3% in those without AKI (P <
      0.01). Conclusion: Peri-operative risk factors for AKI are common among patients
      undergoing major surgery in SSA hospitals. The cumulative incidence of AKI was
      high and independently associated with pre-op sepsis, anaemia, pre-existing
      kidney dysfunction and duration of surgery >120 min.

PMID- 30094008
TI  - Exocrine pancreatic dysfunction is common in hepatocyte nuclear factor 1beta
      associated renal disease and can be symptomatic.
AB  - Background: Heterozygous mutations in the HNF1B gene are the most common
      monogenic cause of developmental kidney disease. Extrarenal phenotypes frequently
      occur, including diabetes mellitus and pancreatic hypoplasia; the latter is
      associated with subclinical exocrine dysfunction. We measured faecal elastase-1
      in patients with HNF1B-associated disease regardless of diabetes status and
      assessed the degree of symptoms associated with pancreatic exocrine deficiency.
      Methods: Faecal elastase-1 was measured in 29 patients with a known HNF1B
      mutation. We defined a low faecal elastase-1 concentration based on the 2.5
      percentile of 99 healthy control individuals (410 MUg/g stool). Symptoms related
      to pancreatic exocrine dysfunction were assessed and a subset of the HNF1B cohort
      (n  =  6) underwent pancreatic imaging. Results: Faecal elastase-1 was below the
      2.5 percentile of the control cohort in 18/29 (62%) patients with HNF1B
      associated renal disease. A total of 8/29 (28%) had a measurement suggestive of
      exocrine pancreatic insufficiency at  <200 MUg/g stool; of these, 3 suffered with
      abdominal pain, loose stools and/or unintentional weight loss. All three
      experienced symptomatic improvement and weight gain after commencing pancreatic
      enzyme replacement therapy. Faecal elastase-1 was low in 7/15 (47%) HNF1B
      patients without diabetes compared with 11/14 (79%) of those with diabetes (P  = 
      0.1). Conclusions: Faecal elastase-1 deficiency is a common feature of HNF1B
      associated renal disease even when diabetes is not present and pancreatic
      exocrine deficiency may be more symptomatic than previously suggested. Faecal
      elastase-1 should be measured in all patients with known HNF1B-associated disease
      complaining of chronic abdominal pain, loose stools or unintentional weight loss.
      The discovery of a low faecal elastase-1 concentration in individuals with
      developmental kidney disease of uncertain cause should prompt referral for HNF1B
      genetic testing.

PMID- 30094009
TI  - Two brothers with identical variants of the CLCN5 gene-one developing Dent's
      disease.
AB  - Dent's disease is characterized by manifestations of proximal tubule dysfunction
      including hypercalciuria, kidney stones, proteinuria, rickets and progressively
      declining kidney function. The diagnosis is based on the presence of low
      molecular-weight proteinuria, hypercalciuria and at least one of the following:
      nephrocalcinosis, kidney stones, haematuria, hypophosphataemia or renal
      insufficiency. Dent's disease is a hereditary condition that is caused by
      variants in the CLCN5 gene or the OCRL1 gene and affects only males. Herein, we
      report on two brothers who were found to have a previously reported disease
      causing variant in the CLCN5 gene. One sibling had nephrocalcinosis, proteinuria
      and hypercalciuria, whereas the other sibling was asymptomatic and had normal
      laboratory findings.

PMID- 30094010
TI  - Seasonal variations in the onset of positive and negative renal ANCA-associated
      vasculitis in Spain.
AB  - Background: The closure of long-standing gaps in our knowledge of aetiological
      factors behind anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis
      (AAV) is a major challenge. Descriptive and analytical epidemiological studies
      can improve our understanding of environmental influences. Reported seasonal
      variations in AAV, mainly related to Wegener's disease, have shown an increasing
      number of cases in the winter months, which could be related to an extrinsic
      factor underlying infection. The objective of this paper was to study seasonal
      variations in AAV with respect to renal affectation diagnosed in Catalonia,
      Spain. Methods: Two hundred and thirty-four patients diagnosed for renal AAV
      between 2001 and 2014 in eight hospitals in Catalonia were included in the study.
      We used medical records to retrospectively analyse the date of the first symptoms
      attributed to the AAV, ANCA subtypes, the degree of renal impairment and renal
      histology. Results: Of the 234 patients studied, 49.2% were male and 50.8%
      female. For ANCA status, 8.5% were positive, 15.9% were proteinase-3-positive and
      75.6% were myeloperoxidase-positive. In relation to histological classification,
      17.8% were sclerotic, 11.7% focal, 38.8% crescentic and 31.7% mixed. Regarding
      seasonal distribution, we observed a clear seasonal periodicity with a
      significantly higher incidence of cases in the winter. Applying an Eigen
      decomposition, we observed a periodic fluctuation of frequencies around the
      annual cycle with peaks every 10-12 months, and higher incidence of AAV cases in
      February. Conclusions: Our results confirm, in Catalonia, the seasonal
      periodicity of AAV with a higher incidence in the winter, as formerly described
      in the literature for other regions. An environmental factor, likely one that is
      infectious, may explain this finding.

PMID- 30094011
TI  - Study protocol: responding to the needs of patients with IgA nephropathy, a
      social media approach.
AB  - Background: IgA nephropathy is the most common cause of glomerulonephritis in the
      Western world and predominantly affects young adults. Demographically these
      patients are the biggest users of social media. With increasing numbers of
      patients turning to social media to seek information and support in dealing with
      their disease, analysis of social media streams is an attractive modern strategy
      for understanding and responding to unmet patient need. Methods: To identify
      unmet patient need in this population, a framework analysis will be undertaken of
      prospectively acquired social media posts from patients with IgA nephropathy,
      acquired from a range of different social media platforms. In collaboration with
      patients and members of the clinical multidisciplinary team, resources will be
      created to bridge gaps in patient knowledge and education identified through
      social media analysis and returned to patients via social media channels and
      bespoke websites. Analysis of the impact of these resources will be undertaken
      with further social media analysis, surveys and focus groups. Conclusions:
      Patients with chronic diseases are increasingly using social networking channels
      to connect with others with similar diseases and to search for information to
      help them understand their condition. This project is a 21st century digital
      solution to understanding patient need and developing resources in partnership
      with patients, and has wide applicability as a future model for understanding
      patient needs in a variety of conditions.

PMID- 30094013
TI  - Meso-American nephropathy: what we have learned about the potential genetic
      influence on chronic kidney disease development.
AB  - Chronic kidney disease of unknown aetiology (CKDu) refers to the epidemic level
      of incidence of CKD in several low- and middle-income countries, usually near the
      equator, for which the aetiology has not been identified. CKDu represents a form
      of CKD hotspot, defined as a country, region, community or ethnicity with a
      higher than average incidence of CKD. In terms of the number of persons affected,
      the so-called hypertensive nephropathy of African Americans probably represents
      the largest CKD hotspot, which is largely driven by variants of the APOL1 gene,
      questioning the very existence of hypertensive nephropathy and illustrating how
      kidney disease driven by genetic predisposition may underlie some forms of
      hypertension. For CKDu, hard physical work leading to dehydration (the first
      global warming-related disease?) and local toxins are leading aetiological
      candidates. Meso-American nephropathy is probably the best-characterized CKDu. In
      this issue of CKJ, a systematic review and meta-analysis by Gonzalez et al.
      identified positive associations between Meso-American nephropathy and male
      gender, family history of CKD, high water intake and lowland altitude. We now
      discuss the potential relationship of family history to genetic predisposition
      and how a better understanding of CKDu may help advance the aetiological
      characterization of the nearly 50% of end-stage renal disease patients worldwide
      that have no known cause for CKD or have been assigned non-specific diagnoses.

PMID- 30094012
TI  - Membranoproliferative glomerulonephritis and C3 glomerulopathy in children:
      change in treatment modality? A report of a case series.
AB  - Background: Membranoproliferative glomerulonephritis (MPGN) with immune complexes
      and C3 glomerulopathy (C3G) in children are rare and have a variable outcome,
      with some patients progressing to end-stage renal disease (ESRD). Mutations in
      genes encoding regulatory proteins of the alternative complement pathway and of
      complement C3 (C3) have been identified as concausative factors. Methods: Three
      children with MPGN type I, four with C3G, i.e. three with C3 glomerulonephritis
      (C3GN) and one with dense deposit disease (DDD), were followed. Clinical,
      autoimmune data, histological characteristics, estimated glomerular filtration
      rate (eGFR), proteinuria, serum C3, genetic and biochemical analysis were
      assessed. Results: The median age at onset was 7.3 years and the median eGFR was
      72 mL/min/1.73 m2. Six children had marked proteinuria. All were treated with
      renin-angiotensin-aldosterone system (RAAS) blockers. Three were given one or
      more immunosuppressive drugs and two eculizumab. At the last median follow-up of
      9 years after diagnosis, three children had normal eGFR and no or mild
      proteinuria on RAAS blockers only. Among four patients without remission of
      proteinuria, genetic analysis revealed mutations in complement regulator proteins
      of the alternative pathway. None of the three patients with immunosuppressive
      treatment achieved partial or complete remission of proteinuria and two
      progressed to ESRD and renal transplantation. Two patients treated with
      eculizumab revealed relevant decreases in proteinuria. Conclusions: In children
      with MPGN type I and C3G, the outcomes of renal function and response to
      treatment modality show great variability independent from histological diagnosis
      at disease onset. In case of severe clinical presentation at disease onset, early
      genetic and biochemical analysis of the alternative pathway dysregulation is
      recommended. Treatment with eculizumab appears to be an option to slow disease
      progression in single cases.

PMID- 30094014
TI  - What do epidemiological studies tell us about chronic kidney disease of
      undetermined cause in Meso-America? A systematic review and meta-analysis.
AB  - Background: The aim of this systematic review is to examine the epidemiological
      knowledge and gaps in understanding of the potential causes of chronic kidney
      disease of undetermined cause (CKDu) in Meso-America. Methods: A systematic
      literature search of epidemiological studies of CKDu was conducted in PubMed,
      Embase and Web of Science from January 2000 to January 2017. Study quality was
      assessed by adapting the tool from Higgins et al. for observational studies.
      Where applicable, the summary prevalence odds ratio (POR) and 95% confidence
      interval (CI) were calculated using a random effects model. Results: Twenty-five
      epidemiological studies were included in the analysis of risk factors for CKDu.
      The quality assessment of each occupational and community study was medium. The
      PORs for CKDu were males versus females 2.42 (95% CI 1.76-3.08), family history
      of CKD (versus none) 1.84 (95% CI 1.37-2.30), high water intake (versus low) 1.61
      (95% CI 1.01-2.21) and low altitude (versus highland) 2.09 (95% CI 1.00-3.17).
      There were no significant associations between CKDu and pesticide exposure
      (versus no) 1.17 (95% CI 0.87-1.46), alcohol consumption (versus no) 1.34 (95% CI
      0.84-1.84), non-steroidal anti-inflammatory drugs (versus no) 0.99 (95% CI 0.60
      1.39) and heat stress (versus no) 1.52 (95% CI -0.91 - 3.95). Conclusion: Our
      meta-analysis showed positive associations for males (versus females) and family
      history of CKD, water intake, lowland altitude and CKDu. There were no
      significant associations with pesticide exposure, non-steroidal anti-inflammatory
      drugs intake, heat stress and alcohol consumption.

PMID- 30094015
TI  - Adherence to medication in patients with chronic kidney disease: a systematic
      review of qualitative research.
AB  - Non-adherence to multipharmacological treatment increases the risk of morbidity,
      mortality and hospitalization. We know little about the perspective of patients
      with chronic kidney disease regarding factors influencing medicine taking. This
      study aimed to synthesize findings from qualitative studies of patients'
      experiences of factors that facilitate and hinder adherence to medication. A
      systematic review of qualitative studies adhering to the Enhancing transparency
      in reporting the synthesis of qualitative research (ENTREQ) framework. Systematic
      searches were conducted in several databases. We used thematic synthesis and the
      Confidence in the Evidence from Reviews of Qualitative Research (CERQual)
      approach to assess the confidence of the evidence. Nineteen studies involving 381
      patients with chronic kidney disease were included. We identified three
      analytical themes; logistics, benchmarking the need for medication; and the
      quality of the patient-physician relationship, with seven descriptive sub-themes
      as factors influencing patients' adherence to medications. Helping patients to
      map their everyday activities and motivating them to associate medications with
      everyday activities may facilitate adherence to medications. Addressing patient
      beliefs about medications, supporting patients in coping with side effects of
      medications and eliciting patients' wishes for involvement in treatment decisions
      may also facilitate adherence. Barriers to adherence were the costs of buying
      medications, and lacking understanding of the indications and effects of
      medications. The findings in this synthesis resonate with previous research and
      extend the known literature by synthesizing and formally assessing confidence in
      the evidence.

PMID- 30094016
TI  - Calciphylaxis in a dialysis patient successfully treated with high-dose vitamin K
      supplementation.
AB  - Calciphylaxis has high mortality. Vitamin K deficiency is common in haemodialysis
      patients and may be a trigger for calciphylaxis due to its role in activating
      matrix Gla protein (a tissue inhibitor of calcification). We report the case of a
      43-year-old female haemodialysis patient who developed calciphylaxis. Two months
      prior to the diagnosis she was found to have an undetectable plasma vitamin K
      concentration. The calciphylaxis completely resolved with vitamin K
      supplementation and an increase in haemodialysis frequency. She did not receive
      sodium thiosulphate or bisphosphonates. Supplementation of vitamin K in deficient
      patients may improve the outcome of this condition.

PMID- 30094017
TI  - Ascorbic acid: a promising agent in chronic kidney disease?
AB  - Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase
      inhibitor, is related with impaired endothelial function and poor outcomes in
      chronic kidney disease (CKD) patients. In addition, oxidative stress and
      inflammation are also a common problem in CKD patients, and both have an
      important role in the development and progression of atherosclerosis and
      increased cardiovascular events in CKD. Ascorbic acid might be a promising agent
      in CKD for improving outcome by decreasing oxidative stress and ADMA levels.

PMID- 30094018
TI  - Ascorbic acid lowers central blood pressure and asymmetric dimethylarginine in
      chronic kidney disease.
AB  - Background: Premature cardiovascular disease in patients with chronic kidney
      disease (CKD) is not explained by traditional risk factors and oxidative stress
      may contribute via endothelial and vascular dysfunction. We investigated the
      effect of ascorbic acid on oxidative stress and vascular function in CKD patients
      compared with controls with hypertension (HTN). Methods: A crossover study of
      intravenous saline and ascorbic acid was conducted. Biomarkers of oxidative
      stress were measured, while pulse wave analysis and brachial flow-mediated
      dilatation were performed to assess large artery and endothelial function.
      Results: Twenty HTN and 30 CKD patients Stages 3-5 were recruited. Serum ascorbic
      acid was significantly lower in patients with CKD. In both groups, ascorbic acid
      significantly increased total antioxidant potential and superoxide. Asymmetric
      dimethylarginine (ADMA) was reduced significantly by ascorbic acid in the CKD
      group and on multivariate regression analysis, age and the presence of CKD were
      predictors of ADMA response to ascorbic acid. Although no effect on FMD was
      observed, central blood pressure and augmentation index were reduced
      significantly in both groups. Conclusions: Ascorbic acid has pro- and antioxidant
      effects, reducing central blood pressure and augmentation index in HTN and CKD.
      Ascorbic acid reduces serum ADMA in CKD, which may have longer-term benefits.

PMID- 30094019
TI  - Acceptability of a multilevel intervention to improve blood pressure control
      among patients with chronic kidney disease in a public health care delivery
      system.
AB  - Background: The Kidney Awareness Registry and Education (KARE) trial examined the
      impact of a multilevel intervention on blood pressure control among patients with
      chronic kidney disease (CKD) in a public health care delivery system. KARE
      consisted of a clinic-based intervention (a primary care CKD registry with point
      of-care provider notifications and quarterly feedback related to CKD management)
      and a patient-directed intervention [a CKD self-management support (CKD-SMS)
      program that included low literacy educational materials, automated telephone
      administered self-management modules and telephone health coaching]. We explored
      the acceptability of these interventions among end users. Methods: At trial
      conclusion, we surveyed 39 primary care providers (PCPs) to identify preferences
      about components of the clinic intervention, conducted two focus groups among non
      PCP staff to elicit in-depth attitudes and experiences with operationalizing the
      team-based CKD registry, and conducted eight focus groups with English- and
      Spanish-speaking patients to hear about their experiences with the CKD-SMS
      program. Focus group transcripts were analyzed using thematic analysis. Self
      reported participation and data from the automated telephone program were used to
      evaluate patient engagement. Results: Most PCPs (94%) believed that the point-of
      care notifications benefited clinic workflow and agreed that quarterly feedback
      enhanced their ability to identify (89.5%) and manage (73.7%) CKD. Staff
      confirmed usefulness of point-of-care notifications. Patients suggested the
      automated telephone system was impersonal, though easy to use; that frequent
      automated calls were helpful to reinforce self-management behaviors; and that
      telephone health coaching was convenient. Nearly 40% of patients completed >80%
      of automated phone calls, 95% participated in calls with their health coach and
      77% created at least one action plan. Conclusions: A CKD registry is acceptable
      to primary care health care teams and has potential to enhance identification and
      management of CKD in primary care. Low-income patients appreciated and engaged
      with a telephone-based CKD-SMS program, demonstrating its potential for
      increasing awareness and health engagement among populations with CKD within a
      public health care delivery system.

PMID- 30094020
TI  - Outcomes of fluoroscopic and ultrasound-guided placement versus laparoscopic
      placement of peritoneal dialysis catheters.
AB  - Background: Several peritoneal dialysis catheter (PDC) placement techniques have
      been described. The objective of this study was to compare the fluoroscopy and
      ultrasound guidance technique with the laparoscopic technique. Methods: We
      retrospectively reviewed the medical records of 260 patients who had their first
      PDC placed between January 2005 and June 2016. We compared the outcomes of the
      fluoroscopic and ultrasound-guided catheter placement technique (radiologic
      group, n = 50) with the laparoscopic catheter placement technique (laparoscopic
      group, n = 190). The primary endpoint was complication-free catheter survival at
      365 days. Secondary endpoints were complication-free catheter survival at 90
      days, overall catheter survival at 90 and 365 days, median days to first
      complication and median days to catheter removal. Results: In the radiologic
      group, the complication-free catheter survival at 90 and 365 days was 64% and
      48%, respectively, while in the laparoscopic group it was 71% (P = 0.374) and 53%
      (P = 0.494), respectively. Catheter malfunction was significantly higher in the
      laparoscopic group (30%) compared with the radiologic group (16%, P = 0.048). The
      overall catheter survival at 90 and 365 days was 76% and 52%, respectively, in
      the radiologic group, while in the laparoscopic group it was 88% (P = 0.0514) an
      48% (P = 0.652), respectively. There was no significant difference in the median
      days to first complication and the median days to catheter removal between the
      two groups (P = 0.71). Conclusion: The technique of fluoroscopic and ultrasound
      guided PDC placement is a clinically effective and safe alternative to
      laparoscopic catheter placement with similar survival and complication rates.

PMID- 30094021
TI  - Online patient resources for deceased donor and live donor kidney recipients: a
      comparative analysis of readability.
AB  - Background: The Internet has extensive resources for kidney transplantation
      recipients. Half of the population reads below a seventh-grade level. Previous
      studies showed that living donor recipients have higher health literacy rates
      compared with deceased donor recipients. There has been no study comparing the
      readability of online living donor recipient materials versus deceased donor
      recipient materials. Methods: Analysis was performed using eight readability
      scales on the top 10 websites for live donor and deceased donor kidney
      transplantation. Analysis was performed through the Readability Studio Software.
      USA reading grade level was determined for each site. Results: Overall, the mean
      reading level for the living donor materials was 12.54 (range 9.2-17) and for the
      deceased donor materials, 12.87 (range 8.7-17, P = 0.73), corresponding to a
      university level. None of the sites met the seventh-grade level recommended by
      the National Institute of Health. Conclusions: The readability of online
      materials remains too high for the corresponding health literacy rates among
      patients requiring kidney transplantation. Specifically, the lower health
      literacy rates among deceased donor recipients does not mirror the readability of
      online materials provided at a university level. This may affect decision-making,
      contributing to a smaller proportion of patients of a lower socioeconomic status
      and those with poor English language skills pursuing live donor organs.

PMID- 30094022
TI  - High frequency of valganciclovir underdosing for cytomegalovirus prophylaxis
      after renal transplantation.
AB  - Background: The correct valganciclovir dose for cytomegalovirus (CMV) prophylaxis
      depends on renal function estimated by the Cockcroft-Gault (CG) estimated
      creatinine clearance (CG-CrCl) formula. Patients with delayed or rapidly changing
      graft function after transplantation (tx) will need dose adjustments. Methods: We
      performed a retrospective investigation of valganciclovir dosing in renal
      transplant patients receiving CMV prophylaxis between August 2003 and August
      2011, and analysed valganciclovir dosing, CG-CrCl, CMV viraemia (CMV-PCR <750
      copies/mL), leucopenia (<3500/uL) and neutropenia (<1500/uL) in the first year
      post-transplant. On Days 30 and 60 post-transplant, dosing pattern in relation to
      estimated creatinine clearance was analysed regarding CMV viraemia, leucopenia
      and neutropenia. Results: Six hundred and thirty-five patients received
      valganciclovir prophylaxis that lasted 129 +/- 68 days with a mean dose of 248 +/
      152 mg/day of whom 112/635 (17.7%) developed CMV viraemia, 166/635 (26.1%)
      leucopenia and 48/635 (7.6%) neutropenia. CMV resistance within 1 year post
      transplant was detected in three patients. Only 137/609 (22.6%) patients received
      the recommended dose, while n = 426 (70.3%) were underdosed and n = 43 (7.1%)
      were overdosed at Day 30 post-tx. Risk factors for CMV viraemia were donor
      positive D (+)/receptor negative R (-) status and short prophylaxis duration, but
      not low valganciclovir dose. Risk factors for developing leucopenia were D+/R-
      status and low renal function. No significant differences in dosing frequency
      were observed in patients developing neutropenia or not (P = 0.584). Conclusion:
      Most patients do not receive the recommended valganciclovir dose. Despite obvious
      underdosing in a large proportion of patients, effective prophylaxis was
      maintained and it was not associated as a risk factor for CMV viraemia or
      leucopenia.

PMID- 30094023
TI  - Hyponatremia in kidney transplant patients: its pathophysiologic mechanisms.
AB  - Kidney transplant patients (KTPs), and particularly those with advanced chronic
      kidney rejection, may be affected by opportunistic infections, metabolic
      alterations and vascular and oncologic diseases that promote clinical conditions
      that require a variety of treatments, the combinations of which may predispose
      them to hyponatremia. Salt and water imbalance can induce abnormalities in
      volemia and/or serum sodium depending on the nature of this alteration (increase
      or decrease), its absolute magnitude (mild or severe) and its relative magnitude
      (body sodium:water ratio). Hyponatremia appears when the body sodium:water ratio
      is reduced due to an increase in body water or a reduction in body sodium.
      Additionally, hyponatremia is classified as normotonic, hypertonic and hypotonic
      and while hypotonic hyponatremia is classified in hyponatremia with normal, high
      or low extracellular fluid. The main causes of hyponatremia in KTPs are hypotonic
      hyponatremia secondary to water and salt contraction with oral hydration
      (gastroenteritis, sepsis), free water retention (severe renal failure, syndrome
      of inappropriate antidiuretic hormone release, hypothyroidism), chronic
      hypokalemia (rapamycin, malnutrition), sodium loss (tubular dysfunction secondary
      to nephrocalcinosis, acute tubular necrosis, tubulitis/rejection, interstitial
      nephritis, adrenal insufficiency, aldosterone resistance, pancreatic drainage,
      kidney-pancreas transplant) and hyponatremia induced by medication (opioids,
      cyclophosphamide, psychoactive, potent diuretics and calcineurinic inhibitors).
      In conclusion, KTPs are predisposed to develop hyponatremia since they are
      exposed to immunologic, infectious, pharmacologic and oncologic disorders, the
      combinations of which alter their salt and water homeostatic capacity.

PMID- 30094024
TI  - A systematic recurrent theme analysis of the reported limitations of facial
      electromyography.
AB  - Background: Advances in digital technology hold promise in expanding the clinical
      and consumer applications of facial electromyography (EMG) through thedevelopment
      of wireless pervasive systems capable of operating in a nonclinical environment.
      This systematic review aims to appraise the most commonly reported limitations of
      the technology in clinical research and practice. Methods: A systematic search
      for clinical facial EMG literature was performed using MEDLINE, EMBASE, PsychINFO
      and CINAHL. No language limits were applied. Search results were screened using
      defined criteria by two authors with disagreements resolved by a third. Practical
      limitations in the technology, as reported by the authors, were recorded and
      characterised using recurrent theme analysis. Results: A total of 4,983 records
      were identified. Of those, 1,061 articles met eligibility criteria and were
      subsequently reviewed. In the medical domain, the most common area of application
      was in psychosocial studies (28% of medical studies); in the surgical domain
      monitoring of facial nerve integrity was the most common application of facial
      electromyography (27% of surgical studies). Collectively, the three most commonly
      reported limitations were motion artefact (13.7%), inter-subject variability in
      response and anatomy (13.1%), and muscle crosstalk (12.0%). Conclusions: This is
      the first study to evaluate the limitations of facial EMG using a systematic
      analysis of author reports. Highlighting technology limitations in this non
      biased manner raises awareness to users key issues and reliably informs the
      development of future systems.

PMID- 30094025
TI  - Burnout among house officers in Myanmar: A cross-sectional study.
AB  - Background: Burnout can result in a serious negative impact on a doctor's life,
      the quality of patient care, and the healthcare organization. This study aims to
      determine the prevalence of burnout and factors affecting burnout among the house
      officers in Myanmar. Materials and methods: An exploratory cross-sectional
      quantitative survey study was conducted using a self-administered, web-based
      survey. House officers working in any of the government hospitals in Myanmar were
      invited to participate in the study. The survey link was distributed online via
      Facebook. To measure burnout, we utilised a non-proprietary single-item measure,
      validated to serve as a reliable substitute for the Maslach Burnout Inventory
      Emotional Exhaustion (MBI:EE). To measure global life satisfaction, the validated
      Satisfaction with Life Scale (SWLS) was used. The questions for the scales
      regarding the psychosocial environment were extracted from the long version of
      the validated Copenhagen Psychosocial Questionnaire (COPSOQ II). The scales
      selected were "possibilities for the development", "meaning of work", "commitment
      to workplace", "recognition", "social support from colleagues" and "social
      support from supervisors". Multiple logistic regression method was applied to
      determine the factors associated with burnout. Results: Regarding the prevalence
      of burnout, out of 159 participants, 42.8% (n = 68) of the participants had no
      symptoms of burnout. 57.2% (n = 91) had one or more symptoms of burnout.
      Multivariate analysis showed that the only significant factor associated with
      burnout was "recognition" (OR 0.96, 95% CI: 0.94-0.97, P < 0.001). Conclusion:
      From this study, we have determined the relatively high burnout prevalence and
      that recognition is the only preventive factor; increase in recognition will
      decrease the odds of burnout. Hence, urgent interventions are recommended to
      prevent undesirable effects on both health professionals and patients.
      Recognition for work done should always be in the heart of the health authorities
      and medical community in Myanmar.

PMID- 30094027
TI  - Evolutionary medicine: Why does prevalence of myopia significantly increase?

PMID- 30094026
TI  - European Core Health Indicators - status and perspectives.
AB  - Background: The European Core Health Indicators (ECHI) are a key source of
      comparable health information for the European Union (EU) and its Member States
      (MS). The ECHI shortlist contains 88 indicators which were developed by experts
      from MS and international organisations. Most indicators are derived from data
      sources at the EU's statistical office (Eurostat), the World Health Organisation
      (WHO) and the Organisation for Economic Co-operation and Development (OECD) and
      are available for most MS. The remaining indicators on the shortlist are at
      different stages of conceptual and/or methodological development. The indicators
      have been reviewed in the past against scientific developments, changes in data
      collections and emerging policy needs, yet not as part of a systematic and
      sustainable procedure. There is also no regular inventory of problems met by the
      MS in collecting the necessary data. Work package 4 of the BRIDGE Health project
      aimed at updating and improving the existing ECHI-indicator knowledge and
      expertise and at strengthening the scientific base that supports the effective
      development and use of health indicators for health policy evaluation and
      prioritization by the EU and its MS. The aim of this paper is to present a first
      overview of its outcomes and to explore issues concerning the ECHI data
      availability, content and policy relevance, update process and accessibility to
      stakeholders, in light of working towards a sustainable future. Methods: Two
      surveys were conducted within the framework of the BRIDGE Health project to
      reassess the status of the ECHI shortlist. The first survey focused on data
      availability in EU MS, candidate countries and European Free Trade Association
      (EFTA) countries. The second survey evaluated current needs and criteria with
      respect to content and policy relevance of the ECHI shortlist. Exploring
      potential new indicator topics was part of both surveys. All evaluations were
      supported by an advisory network of national and international experts. Results:
      Of the 36 countries (EU MS, candidate and EFTA countries) contacted for the data
      availability mapping, 23 countries (63%) participated in the survey. Data
      availability from preferred data sources varied between chapters. Availability
      was highest for the chapter on demography and socio-economic situation, followed
      by the chapter on health status, where data were available for most indicators
      from more than 90% of the participating countries. Problems experienced by MS
      relating to the incorporation of ECHI into their health systems were also
      identified through the survey. Findings from the survey on policy relevance point
      at the need for strengthening the links with policy (priorities) and for
      exploring a possible format change of the list to accommodate actionability. It
      also showed support for embedding ECHI in a sustainable health information
      structure; this may practically be aided by a web-based single point of access to
      an information repository. Conclusion: Policy relevance is an essential but not
      systematically developed criterion for the inclusion of indicators into the ECHI
      shortlist. Data availability is crucial for the actual implementation of
      indicators and has considerably increased for ECHI in the last decade. The data
      availability mapping provides a structured overview of the current status of data
      availability for implemented indicators. The ECHI shortlist can contribute to the
      collection of comparable policy-relevant health data in Europe, foster evidence
      based public health and contribute to Member States learning from each other.
      Flexible and systematic incorporation of policy relevance in the ECHI shortlist
      review and revision process may substantiate ECHI as a core component of a future
      sustainable European health information infrastructure.

PMID- 30094028
TI  - Pembrolizumab-induced myasthenia gravis with myositis in a patient with lung
      cancer.
AB  - In the new era of cancer immunotherapy, clinical research has uncovered diverse
      and unpredictable immune-related adverse events. Here, we report the first case
      of pembrolizumab-induced myasthenia gravis (MG) and myositis in a patient with
      lung cancer. The patient developed symptoms after the second infusion of
      pembrolizumab and was successfully treated with systemic corticosteroid therapy.
      With the accelerated development of immune checkpoint inhibitors as mono- or
      combination therapies for various malignancies, clinicians should closely monitor
      patients for important immune-related adverse events, such as MG, especially
      during the early phase of the treatment.

PMID- 30094029
TI  - Exogenous lipoid pneumonia: an important cause of interstitial lung disease in
      infants.
AB  - Exogenous lipoid pneumonia (ELP), an important cause of interstitial lung
      disease, often goes unrecognized. We conducted a retrospective study of children
      with histologically confirmed ELP at Red Cross Children's Hospital, South Africa.
      Twelve children of Zimbabwean heritage aged 2.1-10.8 months were identified
      between 2012 and 2017. Repeated oral administration of plant-based oil for
      cultural reasons was reported by 10 of 11 caregivers. Cough (12/12), tachypnoea
      (11/12), hypoxia (9/12), and diffuse alveolar infiltrates on chest radiography
      (12/12) were common at presentation. Chest computed tomography revealed ground
      glass opacification with lower zone predominance (9/9) and interlobular septal
      thickening (8/9). Bronchoalveolar lavage specimens appeared cloudy/milky, with
      abundant lipid-laden macrophages and extracellular lipid on Oil-Red-O staining
      (12/12), with polymicrobial (6/12) and Mycobacterium abscessus (2/12) co
      infection. Antibiotics, systemic corticosteroids, and therapeutic lavage were
      interventions in all eight and five patients, respectively. Clinicians should
      consider ELP in children with non-resolving pneumonia in settings with similar
      practices.

PMID- 30094030
TI  - Preliminary guideline- and pathophysiology-based protocols for neurocritical
      care.
AB  - Background: Because of the complex pathophysiological processes involved,
      neurocritical care has been driven by anecdotal experience and physician
      preferences, which has led to care variation worldwide. Standardization of
      practice has improved outcomes for many of the critical conditions encountered in
      the intensive care unit. Main body: In this review article, we introduce
      preliminary guideline- and pathophysiology-based protocols for (1) prompt
      shivering management, (2) traumatic brain injury and intracranial pressure
      management, (3) neurological prognostication after cardiac arrest, (4) delayed
      cerebral ischemia after subarachnoid hemorrhage, (5) nonconvulsive status
      epilepticus, and (6) acute or subacute psychosis and seizure. Conclusion: These
      tentative protocols may be useful tools for bedside clinicians who need to
      provide consistent, standardized care in a dynamic clinical environment. Because
      most of the contents of presented protocol are not supported by evidence, they
      should be validated in a prospective controlled study in future. We suggest that
      these protocols should be regarded as drafts to be tailored to the systems,
      environments, and clinician preferences in each institution.

PMID- 30094032
TI  - Perceptions of the Malaysian general public on community pharmacy-based weight
      management services.
AB  - Background: Obesity is now widely regarded as a main contributor to poor health.
      Involvement of community pharmacists can be a valuable tool in obesity
      management. However, there is still a lack of data in Malaysia on the potential
      involvement of and opportunities for community pharmacists in providing weight
      management services. Thus, it is essential to investigate the perceptions of the
      general public on weight management services in the community pharmacy setting.
      To evaluate the general public's perceptions on weight management services by
      community pharmacists in terms of perceived availability, utilization and factors
      influencing acceptability of services. Methods: A descriptive, cross sectional
      survey was conducted using a self-administered questionnaire comprising of
      sections that focused on public preferences and options on weight management
      approaches, perceived availability of extended services and resources provided by
      community pharmacists in relation to weight management, utilization of these
      services and resources, and factors influencing acceptability of weight
      management services provided by community pharmacists. The questionnaires were
      distributed to the general public aged 18 years and above in Klang Valley,
      Malaysia. Results: A total of 730 respondents with a median age of 31 years
      participated in this study. Majority of respondents ranked dieticians as their
      preferred first line of consultation, with only about a quarter of respondents
      ranking community pharmacists as their preferred first or second line of
      consultation. Although more than half show of the study respondents perceived
      that community pharmacies they had visited offered services for measuring weight,
      height, blood pressure, blood glucose and blood cholesterol, fewer perceived that
      community pharmacies provided advice on physical activity and healthy eating to
      achieve weight loss. Additionally, majority of the respondents indicated that
      they had not utilized these services. However, most respondents perceived that
      community pharmacists should provide weight management services. The main factors
      influencing acceptability show of services included training of pharmacists,
      payment, waiting time and the issue of privacy. Conclusion: The findings of this
      study demonstrated that the majority of respondents were in support of weight
      management services in community pharmacy; however only a low percentage reported
      utilizing these services. Factors influencing acceptability of services included
      payment, waiting time and the issue of privacy. With adequate training among
      pharmacists and increased awareness of services among the public, community
      pharmacists could play a larger and important role in addressing the issue of
      obesity in Malaysia.

PMID- 30094031
TI  - Pathogenicity locus determinants and toxinotyping of Clostridioides difficile
      isolates recovered from Iranian patients.
AB  - Little is known about the toxin profiles, toxinotypes and variations of toxin
      Clostridioides difficile C (tcdC) in Iranian C. difficile isolates. A total of
      818 stool specimens were obtained from outpatients (n = 45) and hospitalized
      patients (n = 773) in Tehran, Iran, from 2011 to 2017. The 44 C. difficile
      isolates were subjected to PCR of toxin C. difficile A (tcdA), toxin C. difficile
      B (tcdB), tcdA 3'-end deletion, toxinotyping and sequencing of the tcdC gene.
      Thirty-eight isolates (86.36%) were identified as tcdA and tcdB positive, and the
      remaining six isolates (13.63%) were nontoxigenic. All tcdA- and tcdB-positive
      isolates yielded an amplicon of 2535 bp by PCR for the tcdA 3' end. Fourteen
      (36.84%), seventeen (44.73%) and seven (18.43%) isolates belonged to wild-type,
      toxin C. difficile C subclone3 (tcdC-sc3) and tcdC-A genotype of tcdC,
      respectively. Thirty-one isolates (81.57%) belonged to toxinotype 0, and seven
      isolates (18.42%) were classified as toxinotype V. This study provides evidence
      for the circulation of historical and hypervirulent isolates in the healthcare
      and community settings. Furthermore, it was also demonstrated that the tcdC-A
      genotype and toxinotype V are not uncommon among Iranian C. difficile isolates.

PMID- 30094033
TI  - The roles of doctors, nurses, and industrial hygienists in the healthcare
      management services in Korea: a comparison of the opinions of specialized health
      management institutions and entrusted enterprises.
AB  - Background: This study aimed to identify the difference of perception about the
      role of appointing health officers by comparing and analyzing the response of
      entrustment workplace (EW) and specialized health management institution (SI).
      This is considered an important aspect of an institutional assessment to improve
      the quality of health management services. Methods: A survey questionnaire was
      mailed to 122 SIs and 319 EWs nationwide. The questionnaire survey was about the
      general characteristics of SIs and EWs and main occupations for each evaluation
      item. In total, 81 SIs (66.4%) and 30 EWs responded to the questionnaire. A
      logistic regression analysis was performed to compare the opinions of SI and EW.
      Results: Based on the analysis, the items showing statistically significant
      differences were as follows. Doctors' main tasks survey: "Guidance on their
      wearing personal protective equipment (PPE)" (OR: 4.58), "Guidance of improvement
      of work environment (WE)" (OR: 3.33), etc.; Nurses' main tasks survey: "Guidance
      on their wearing PPE" (OR: 3.86), "Guidance for programs on health process in
      confined space (CS)" (OR: 0.36), "Guidance on the hearing conservation program
      (HCP)" (OR: 0.28), etc.; Industrial hygienist (IH)'s main tasks survey: "Guidance
      of work through inspection (WTI)" (OR: 0.15), "Guidance on the improvement of WE"
      (OR: 0.32), "Management confirmation of substances used by process and Material
      Safety Data Sheet (MSDS)" (OR: 0.08), "Guidance on posting or keeping of MSDS and
      warning signs" (OR: 0.03), "Prevention of dust-induced medical problems" (OR:
      0.28), "Guidance for programs of health process in CS" (OR: 0.39), etc.
      Conclusions: It is necessary to educate the EWs to recognize the need for
      physicians to perform tasks, such as wearing a PPE, and instruction to improve
      WE. As for nurses' tasks, such as education about the CS and the noise work,
      educating the nurses of the SI is regarded necessary as the demand of the EWs is
      considered. With respect to the unique tasks of IH, such as WE management and
      instructions for wearing PPE, among several other tasks of IH, training should be
      provided for improved IH recognition.

PMID- 30094034
TI  - Cardiotoxicity: precision medicine with imprecise definitions.

PMID- 30094036
TI  - Transcatheter aortic valve implantation in decompensated aortic stenosis within
      the same hospital admission: early clinical experience.
AB  - Objective: Severe decompensated aortic valve stenosis is associated with
      noticeable reduction in survival. Until recently the options for such patients
      were either high-risk surgery or percutaneous balloon valvuloplasty and medical
      therapy which does not add any survival benefits and associated with high rate of
      complications. We present our experience in the use of transcatheter aortic valve
      implantation (TAVI) in patients with decompensated severe aortic stenosis
      requiring urgent intervention in the same hospital admission. Methods: In this
      observational study, all patients who were admitted with decompensated severe
      aortic stenosis were enrolled. Elective patients were excluded from the study.
      Perioperative records were analysed and clinical, echocardiographic and survival
      data were presented. Results: 76 patients with a mean age of 81+/-6 years were
      enrolled. All patients presented with New York Heart Association (NYHA) IV
      status. Femoral approach was performed in 86.8%. Median postoperative hospital
      stay was 6 days and intensive care unit admission rate was 15%. At follow-up,
      61.8% of patients were in NYHA status I/II. Moderate or more paravalvular leak
      occurred in 5.2% of patients. Permanent pacemaker was required in 14.4% of
      patients. The incidence of in-hospital death was 2.6%. Kaplan-Meier analysis
      indicated a survival rate of 81% at 1 year. Conclusions: Urgent in-hospital TAVI
      is feasible as the first-line treatment in decompensated severe aortic stenosis.
      In our cohort, it showed to be safe and achieved satisfactory survival rates and
      symptom control.

PMID- 30094035
TI  - Contemporary outcomes of isolated bioprothestic mitral valve replacement for
      mitral regurgitation.
AB  - Background: Early experience with transcatheter mitral valve replacement (TMVR)
      highlighted several investigational challenges related to this novel therapy.
      Conclusive randomised clinical trials in the field may, therefore, be years
      ahead. In the interim, contemporary outcomes of isolated surgical bioprosthetic
      mitral valve replacement (MVR) can be used as a benchmark for the emerging TMVR
      therapies. Methods: We used the nationwide inpatient sample to examine recent
      trends and outcomes of surgical bioprosthetic MVR for mitral regurgitation
      (isolated and combined). Results: 21 007 patients who had bioprosthetic MVR
      between 2003 and 2014 were included. Of those, 30% had isolated MVR and 70% had
      concomitant cardiac surgical procedure(s). In patients who underwent isolated
      bioprothestic MVR, mean age was 68+/-13, and females were the majority (58.4%).
      Most of these procedures were performed at teaching institutions (71.3%) and
      during an elective admission (64%). In-hospital mortality improved during the
      study period (7.8% in 2003 to 4.7% in 2014, p trend=0.016). Postoperative
      morbidities were common; permanent pacemaker 11.7%, stroke 2.4%, new dialysis
      4.9% and blood transfusion 41.6%. Mean length of stay was 13+/-12 days, and 27.2%
      of patients were discharged to an intermediate care of rehabilitation facility.
      Cost of hospitalisation was $62 443+/-50 997. Conclusions: Isolated bioprosthetic
      MVR for mitral regurgitation is performed infrequently but is associated with
      significant in-hospital morbidity and mortality and cost in contemporary
      practice. These data are useful as benchmarks for the evolving TMVR therapies.

PMID- 30094037
TI  - Applying the ordinal model of atherosclerosis to imaging science: a brief review.
AB  - Atherogenesis has been well demonstrated to proceed in an ordinal fashion.
      Imaging technologies have advanced substantially in recent decades, enabling
      early detection of atherosclerosis. Some modalities, such as coronary CT, have
      seen broad clinical adaptation. In contrast, others, such as flow-mediated
      dilatation, remain predominantly research-based. Optimal and appropriate usage of
      these technologies remains an area of active investigation. We hypothesise that
      investigators ought to consider which stage of atherosclerosis is under
      investigation when choosing imaging modalities. Additionally, when assessing the
      efficacy of a particular treatment, some imaging modalities may be more
      appropriate than others. We review the most important available imaging
      modalities and suggest stages at which each may or may not be well used.
      Conceptual application of the classic stages of atherosclerosis model to the
      variety of modern imaging modalities available will result in more effective
      investigation and treatment of cardiovascular disease.

PMID- 30094038
TI  - Effects of dietary fats on blood lipids: a review of direct comparison trials.

PMID- 30094039
TI  - Measuring lupus arthritis activity using contrasted high-field MRI. Associations
      with clinical measures of disease activity and novel patterns of disease.
AB  - Objective: Arthritis in SLE is poorly described, and there is no objective
      measure for quantification of arthritis. In this pilot study, we aim to assess
      the utility of the Rheumatoid Arthritis MRI Scoring System (RAMRIS) for the
      quantification of lupus arthritis. Methods: Patients were eligible for entry into
      the study if they were evaluated at the Medical University of South Carolina
      Lupus Center and determined by their treating rheumatologist to have active hand
      arthritis due to SLE. Standard of care lupus activity measures were collected,
      along with a detailed physical exam. MRIs were obtained using standard
      musculoskeletal sequences with gadolinium contrast. Semiquantitative scoring of
      the images used the Outcome Measures in Rheumatology Clinical Trials RAMRIS
      system. Results: RAMRIS demonstrates large amounts of synovitis, tenosynovitis,
      bone marrow oedema and erosive disease in only a minority of patients. Some
      patients were not scored as having any synovitis or tenosynovitis. We describe
      potential features of lupus arthritis that are not captured in the RAMRIS scores
      and may be contributing to symptoms. Conclusion: Lupus arthritis is an entity
      separate from rheumatoid arthritis and requires the development of new
      quantitative methods to describe and quantitate it. MRI findings suggest the
      inadequacy of a typical lupus musculoskeletal measure including swollen/tender
      joint counts to assess the level of disease activity.

PMID- 30094040
TI  - Myocarditis in systemic lupus erythematosus diagnosed by 18F-fluorodeoxyglucose
      positron emission tomography.
AB  - Objectives: Cardiovascular diseaseand heart failure (CHF) are leading causes of
      death in systemic lupus erythematosus (SLE). The underlying mechanisms for
      increased CHF in SLE are unclear but myocardial inflammation and lupus
      myocarditis (LM) may play a role. We propose that 18F-fluorodeoxyglucose-positron
      emission tomography (18F-FDG-PET)/CT can help diagnose LM. Methods: This report
      describes eight patients with presumed LM; five patients were evaluated due to
      active cardiorespiratory symptoms and three patients were participating in a
      pilot study to determine the prevalence of subclinical myocarditis in SLE.
      Clinical characteristics, laboratory and cardiac testing including
      electrocardiography (ECG), transthoracic echocardiogram (TTE), coronary artery
      evaluation as well as 18F-FDG-PET/CT imaging are discussed. Results: Four
      patients were African American and the others were Hispanic. Half presented with
      chest pain; 37% had dyspnoea and 25% were asymptomatic. The median SLE Disease
      Activity Index (SLEDAI-2K) was 5 (2-18) and SLICC Damage Index (SDI) 0.5 (0-5).
      The median troponin level was 0.08 ng/mL (0-0.9). The most common ECG findings
      were non-specific ST-T wave abnormalities (n=5). Fifty per cent of the patients
      had a decreased ejection fraction on TTE and all patients had diffuse myocardial
      FDG uptake on 18F-FDG-PET/CT consistent with myocardial inflammation. Conclusion:
      This case series is the first to describe the use of 18F-FDG-PET/CT in the
      diagnosis of LM and discuss the clinical characteristics and cardiac findings of
      eight patients with LM supporting the role for cardiac 18F-FDG-PET/CT in its
      diagnosis.

PMID- 30094042
TI  - Case report: the role of OCT in examination of a patient with topiramate-induced
      acute angle closure, acute myopia and macular striae.
AB  - This work reports on a clinical case of a female who presented with headache,
      bilateral eye pain and vision loss. Intraocular pressures were 40 mm Hg in the
      right eye and 45 mm Hg in the left eye. Optical Coherence Tomography examination
      shows the iridocorneal angle was collapsed and macular striae were also observed.
      The patient had been on topiramate due to migraines 7 days before presentation.
      Diagnosis for topiramate-induced acute angle closure was made in both eyes. The
      patient showed improvement in symptoms a few days after treatment initiation and
      images confirmed that the iridocorneal angle had been enlarged and macular striae
      had disappeared.

PMID- 30094043
TI  - The nerve of legal entrapment.
AB  - Chordomas are a rare type of bone tumor that arises from the embryological
      remnant of the notochord. They originate at any point along the axial spine with
      the sacrum and the skull based region being the most commonly affected sites.
      Chordomas are slowly growing, indolent tumors, presenting insidiously, but also
      carry a high recurrence rate with a tendency to invade contiguous structure
      making their treatment challenging. The current standard of care for localized
      chordoma is aggressive cytoreductive surgery followed by high dose adjuvant
      radiotherapy. We present a unique case of a 72-year-old lawyer with a skull base
      chordoma invading into the hypoglossal canal and causing isolated hypoglossal
      nerve paralysis.

PMID- 30094044
TI  - Three vessel coronary artery-left ventricular multiple micro-fistulas: a rare
      angiographic finding.
AB  - A 54-year-old woman presents with a long history exertional chest pain and was
      found to have left ventricular systolic dysfunction on trans-thoracic
      echocardiogram. Coronary angiography revealed no evidence of atherosclerotic
      coronary artery disease and showed multiple micro-fistulae draining from all
      three major coronary arteries to the left ventricle. This rare abnormality is the
      result of failure of obliteration of intra-trabecular embryonic sinusoids and may
      cause myocardial ischemia through the coronary steal mechanism.

PMID- 30094041
TI  - DNA methylation 101: what is important to know about DNA methylation and its role
      in SLE risk and disease heterogeneity.
AB  - SLE is a complex autoimmune disease that results from the interplay of genetics,
      epigenetics and environmental exposures. DNA methylation is an epigenetic
      mechanism that regulates gene expression and tissue differentiation. Among all
      the epigenetic modifications, DNA methylation perturbations have been the most
      widely studied in SLE. It mediates processes relevant to SLE, including
      lymphocyte development, X-chromosome inactivation and the suppression of
      endogenous retroviruses. The establishment of most DNA methylation marks occurs
      in utero; however, a small percentage of epigenetic marks are dynamic and can
      change throughout a person's lifetime and in relation to exposures. In this
      review, we discuss the current understanding of the biology of DNA methylation
      and its regulators, the measurement and interpretation of methylation marks, the
      effects of genetics on DNA methylation and the role of environmental exposures
      with relevance to SLE. We also summarise research findings associated with SLE
      disease risk and heterogeneity. The robust finding of hypomethylation of
      interferon-responsive genes in patients with SLE and new associations beyond
      interferon-responsive genes such as cell-specific methylation abnormalities are
      described. We also discuss methylation changes associated with lupus nephritis,
      autoantibody status and disease activity. Lastly, we explore future research
      directions, emphasising the need for longitudinal studies, cell tissue and
      context-specific profiling, as well as integrative approaches. With new
      technologies, DNA methylation perturbations could be targeted and edited,
      offering novel therapeutic approaches.

PMID- 30094046
TI  - Neurocognitive functioning is associated with functional independence in newly
      diagnosed patients with temporal lobe glioma.
AB  - Background: Cancer and treatment-related neurocognitive dysfunction has the
      potential to significantly disrupt the lives of survivors. While neurocognitive
      functioning is known to predict aspects of patient-reported quality of life in
      individuals with glioma, little is known regarding the association between
      neurocognitive functioning and clinician-rated functional independence. Methods:
      Newly diagnosed patients with glioma in the left (n = 73; 49% glioblastoma) or
      right (n = 30; 57% glioblastoma) temporal lobe completed comprehensive
      neuropsychological testing. Clinicians rated patient functional independence
      using the Functional Independence Measure (FIM) and Karnofsky Performance Status
      (KPS) scale. Correlational and regression analyses were conducted to determine
      relationships between neurocognitive functioning and functional independence.
      Results: Tests of verbal learning, executive function, and language comprehension
      were moderately to strongly associated with clinician-rated functional
      independence, particularly for items pertaining to need for assistance with
      memory, problem-solving, and language functions. Stepwise linear regression
      showed that tests of verbal learning, executive functioning, and language
      comprehension predicted FIM ratings, together accounting for 40% of variance (P <
      .001). A test of executive functioning also predicted KPS scores and accounted
      for 19% of variance (P < .001). Conclusions: In patients with newly diagnosed
      temporal lobe glioma, neurocognitive functioning is associated with functional
      independence. Verbal learning, executive functioning, and language comprehension
      demonstrated the strongest associations across both measures of functional
      independence. These findings provide support for the ecological validity of
      neuropsychological assessment by demonstrating the real-world clinical
      significance of objectively assessed neurocognitive functioning in glioma
      patients.

PMID- 30094045
TI  - Incidence trends, rates, and ethnic variations of primary CNS tumors in Texas
      from 1995 to 2013.
AB  - Background: Although rare, primary central nervous system (CNS) tumors are
      associated with significant morbidity and mortality. Texas is a representative
      sample of the United States population given its large population, ethnic
      disparities, geographic variations, and socio-economic differences. This study
      used Texas data to determine if variations in incidence trends and rates exist
      among different ethnicities in Texas. Methods: Data from the Texas Cancer
      Registry from 1995 to 2013 were examined. Joinpoint Regression Program software
      was used to obtain the incidence trends and SEER*Stat software was used to
      produce average annual age-adjusted incidence rates for both nonmalignant and
      malignant tumors in Texas from 2009 to 2013. Results: The incidence trend of
      malignant primary CNS tumors in whites was stable from 1995 to 2002, after which
      the annual percent change decreased by 0.99% through 2013 (95% CI, -1.4, -0.5; P
      = .04). Blacks and Asian/Pacific Islanders showed unchanged incidence trends from
      1995 to 2013. Hispanics had an annual percent change of -0.83 (95% CI, -1.4, 
      0.2; P = .009) per year from 1995 through 2013. From 2009 to 2013, the incidence
      rates of nonmalignant and malignant primary CNS tumors were highest among blacks,
      followed by whites, Hispanics, Asians, and American Indians/Alaskan Natives.
      Conclusions: Consistent with the 2016 Central Brain Tumor Registry of the United
      States report, the black population in Texas showed the highest total incidence
      of CNS tumors of any other race studied. Many factors have been proposed to
      account for the observed differences in incidence rate including geography,
      socioeconomic factors, and poverty factors, although the evidence for these
      external factors is lacking.

PMID- 30094047
TI  - Returning research results: caregivers' reactions following computerized
      cognitive training among childhood cancer survivors.
AB  - Background: Few researchers routinely disseminate results to participants;
      however, there is increasing acknowledgment that benefits of returning results
      outweigh potential risks. Our objective was to determine whether use of specific
      guidelines developed by the Children's Oncology Group (COG) when preparing a lay
      summary would aid in understanding results. Specifically, to determine if
      caregivers of childhood cancer survivors found a lay summary comprehensive, easy
      to understand, and helpful following participation in a computerized cognitive
      training program. Methods: In a previous study, 68 childhood survivors of acute
      lymphoblastic leukemia or brain tumor with identified cognitive deficits were
      randomly assigned to participate in a computerized cognitive intervention or
      assigned to a wait list. Following conclusion of this study, participants'
      caregivers were contacted and provided with a summary of results based on COG
      guidelines and survey. Forty-three participants returned the surveys, examining
      caregivers' interpretation of the summary, reaction to the results, and
      information regarding preference for receiving results. Results: Caregivers
      reported results as important (93%), helpful (93%), easy to understand (98%), and
      relevant to their child (91%). They interpreted the results as generally
      positive, with many caregivers endorsing satisfaction (84%); however, concern of
      long-term implications was expressed (25%). Most preferred receiving results
      through postal letter (88%) or email (47%). Conclusions: Benefits of returning
      research results to families appear to outweigh potential negative consequences.
      Returning results may help inform families when making future health care-related
      decisions. There is a great need to develop and assess the utility of guidelines
      for returning research results.

PMID- 30094048
TI  - Women's experiences of managing digitation: do we ask enough in primary care?
AB  - The aim of this paper was to consider the available evidence for the current
      management of pelvic organ prolapse, which is a common presentation in primary
      care. However, not all women will present, only presenting when symptoms become
      bothersome. Particular attention was paid to understanding the problem of
      rectocele and its influence on obstructive defaecation symptoms. The burden of
      rectocele and its consequences are not truly known. Furthermore, healthcare
      professionals may not always enquire about bowel symptoms and patients may not
      disclose them. Complex emotions around coping and managing stress add to the
      challenges with seeking healthcare. Therefore, the impact on the lived experience
      of women who have difficulty with rectal emptying can be significant. The review
      identified a dearth of knowledge about women living with the problem of
      obstructive defaecation resulting in the use of digitation. Improving the
      management of digitation, an under-reported problem, is necessary to improve the
      quality of life for women. Primary care needs to increase access to conservative
      measures for women struggling with bothersome symptoms, such as constipation, the
      need to digitate or anxiety.

PMID- 30094050
TI  - Late-Onset Systemic Lupus Erythematosus With Lupus Nephritis in a 74-Year-Old
      Male: A Brief Case and Review.
AB  - Rationale: Late-onset systemic lupus erythematosus (SLE) represents a specific
      subgroup of SLE, and although there is no strict age cut-off, 50 years is
      commonly used as the minimum age for disease onset. In this report, we present a
      case of a 74-year-old male with late-onset SLE and biopsy-proven lupus nephritis
      (LN). Presenting concerns of the patient: A 74-year-old male was referred to the
      nephrology clinic with a rapidly rising creatinine from a baseline of 60 umol/L
      to 176 umol/L. His labs showed pancytopenia, a positive antinuclear antibodies
      (ANA), and hypocomplementemia. Diagnoses: Renal biopsy showed focal proliferative
      glomerulonephritis that was immune-mediated and immunofluorescence showed C3,
      IgM, IgA, IgG, lambda, and C1q diffuse mesangial and glomerular basement membrane
      staining. Together these findings were in keeping with a diagnosis of stage III
      LN. Interventions: Treatment included hemodialysis and induction with pulse
      methylprednisone and cyclophosphamide. He was then placed on the Euro-Lupus
      Protocol. Outcomes: One year after the diagnosis, he was off dialysis, had no
      signs of fluid retention or uremia, and his creatinine had stabilized at ~ 330
      umol/L. Lessons learned: To the best of our knowledge, this case represents the
      oldest known biopsy-confirmed case of late-onset SLE and LN. Late-onset SLE is
      uncommon and often overlooked as classical symptoms such as malar rash or
      photosensitivity may not be present. The American College of Rheumatology (ACR)
      guidelines for treatment of LN can be applied to these patients but physicians
      should be cognizant of the fact that these patients may not tolerate
      immunosuppressive therapy as well as younger patients.

PMID- 30094049
TI  - Prediction of Acute Kidney Injury With a Machine Learning Algorithm Using
      Electronic Health Record Data.
AB  - Background: A major problem in treating acute kidney injury (AKI) is that
      clinical criteria for recognition are markers of established kidney damage or
      impaired function; treatment before such damage manifests is desirable.
      Clinicians could intervene during what may be a crucial stage for preventing
      permanent kidney injury if patients with incipient AKI and those at high risk of
      developing AKI could be identified. Objective: In this study, we evaluate a
      machine learning algorithm for early detection and prediction of AKI. Design: We
      used a machine learning technique, boosted ensembles of decision trees, to train
      an AKI prediction tool on retrospective data taken from more than 300 000
      inpatient encounters. Setting: Data were collected from inpatient wards at
      Stanford Medical Center and intensive care unit patients at Beth Israel Deaconess
      Medical Center. Patients: Patients older than the age of 18 whose hospital stays
      lasted between 5 and 1000 hours and who had at least one documented measurement
      of heart rate, respiratory rate, temperature, serum creatinine (SCr), and Glasgow
      Coma Scale (GCS). Measurements: We tested the algorithm's ability to detect AKI
      at onset and to predict AKI 12, 24, 48, and 72 hours before onset. Methods: We
      tested AKI detection and prediction using the National Health Service (NHS)
      England AKI Algorithm as a gold standard. We additionally tested the algorithm's
      ability to detect AKI as defined by the Kidney Disease: Improving Global Outcomes
      (KDIGO) guidelines. We compared the algorithm's 3-fold cross-validation
      performance to the Sequential Organ Failure Assessment (SOFA) score for AKI
      identification in terms of area under the receiver operating characteristic
      (AUROC). Results: The algorithm demonstrated high AUROC for detecting and
      predicting NHS-defined AKI at all tested time points. The algorithm achieves
      AUROC of 0.872 (95% confidence interval [CI], 0.867-0.878) for AKI detection at
      time of onset. For prediction 12 hours before onset, the algorithm achieves an
      AUROC of 0.800 (95% CI, 0.792-0.809). For 24-hour predictions, the algorithm
      achieves AUROC of 0.795 (95% CI, 0.785-0.804). For 48-hour and 72-hour
      predictions, the algorithm achieves AUROC values of 0.761 (95% CI, 0.753-0.768)
      and 0.728 (95% CI, 0.719-0.737), respectively. Limitations: Because of the
      retrospective nature of this study, we cannot draw any conclusions about the
      impact the algorithm's predictions will have on patient outcomes in a clinical
      setting. Conclusions: The results of these experiments suggest that a machine
      learning-based AKI prediction tool may offer important prognostic capabilities
      for determining which patients are likely to suffer AKI, potentially allowing
      clinicians to intervene before kidney damage manifests.

PMID- 30094051
TI  - Exhaled biomarkers in childhood asthma: old and new approaches.
AB  - Background: Asthma is a chronic condition usually characterized by underlying
      inflammation. The study of asthmatic inflammation is of the utmost importance for
      both diagnostic and monitoring purposes. The gold standard for investigating
      airway inflammation is bronchoscopy, with bronchoalveolar lavage and bronchial
      biopsy, but the invasiveness of such procedures limits their use in children. For
      this reason, in the last decades there has been a growing interest for the
      development of noninvasive methods. Main body: In the present review, we describe
      the most important non-invasive methods for the study of airway inflammation in
      children, focusing on the measure of the fractional exhaled nitric oxide (feNO),
      on the measure of the exhaled breath temperature (EBT) and on the analysis of
      both exhaled breath condensate (EBC) and exhaled air (Volatile Organic Compounds,
      VOCs), using targeted and untargeted approaches. We summarize what is currently
      known on the topic of exhaled biomarkers in childhood asthma, with a special
      emphasis on emerging approaches, underlining the role of exhaled biomarkers in
      the diagnosis, management and treatment of asthma, and their potential for the
      development of personalized treatments. Conclusion: Among non-invasive methods to
      study asthma, exhaled breath analysis remains one of the most interesting
      approaches, feNO and "-omic" sciences seem promising for the purpose of
      characterizing biomarkers of this disease.

PMID- 30094052
TI  - Recent trends, risk factors, and disparities in low birth weight in California,
      2005-2014: a retrospective study.
AB  - Background: Low birth weight (LBW) is a leading risk factor for infant morbidity
      and mortality in the United States. There are large disparities in the prevalence
      of LBW by race and ethnicity, especially between African American and White
      women. Despite extensive research, the practice of clinical and public health,
      and policies devoted to reducing the number of LBW infants, the prevalence of LBW
      has remained unacceptably and consistently high. There have been few detailed
      studies identifying the factors associated with LBW in California, which is home
      to a highly diverse population. The aim of this study is to investigate recent
      trends in the prevalence of LBW infants (measured as a percentage) and to
      identify risk factors and disparities associated with LBW in California. Methods:
      A retrospective cohort study included data on 5,267,519 births recorded in the
      California Birth Statistical Master Files for the period 2005-2014. These data
      included maternal characteristics, health behaviors, information on health
      insurance, prenatal care use, and parity. Logistic regression models identified
      significant risk factors associated with LBW. Using gestational age based on
      obstetric estimates (OA), small for gestational age (SGA), appropriate for
      gestational age (AGA) and large for gestational age (LGA) infants were identified
      for the periods 2007-2014. Results: The number of LBW infants declined, from
      37,603 in 2005 to 33,447 in 2014. However, the prevalence of LBW did not change
      significantly (6.9% in 2005 to 6.7% in 2014). The mean maternal age at first
      delivery increased from 25.7 years in 2005 to 27.2 years in 2014. The adjusted
      odds ratio showed that women aged 40 to 54 years were twice as likely to have an
      LBW infant as women in the 20 to 24 age group. African American women had a
      persistent 2.4-fold greater prevalence of having an LBW infant compared with
      white women. Maternal age was a significant risk factor for LBW regardless of
      maternal race and ethnicity or education level. During the period 2017-2014, 5.4%
      of the singleton births at 23-41 weeks based on OE of gestational age were SGA
      infants (preterm SGA + term SGA). While all the preterm SGA infants were LBW,
      both preterm AGA and term SGA infants had a higher prevalence of LBW.
      Conclusions: In California, during the 10 years from 2005 to 2014, there was no
      significant decline in the prevalence of LBW. However, maternal age was a
      significant risk factor for LBW regardless of maternal race and ethnicity or
      education level. Therefore, there may be opportunities to reduce the prevalence
      of LBW by reducing disparities and improving birth outcomes for women of advanced
      maternal age.

PMID- 30094053
TI  - Risk factors for oxaliplatin-induced vascular pain in patients with colorectal
      cancer and comparison of the efficacy of preventive methods.
AB  - Background: Vascular pain is a common adverse drug reaction in colorectal cancer
      patients receiving peripheral venous administration of oxaliplatin. The aim of
      this work was to identify risk factors for vascular pain, and to examine whether
      currently used treatments reduce its incidence. Methods: We conducted a
      multicenter retrospective study in Japanese colorectal cancer patients receiving
      peripheral venous administration of oxaliplatin. The effects of various
      treatments (administration of analgesics, addition of dexamethasone to the
      infusion solution for pH adjustment, dilution of the infusion solution, or use of
      hot gel for warming the injection site) on the incidence of vascular pain were
      assessed. Risk factors for vascular pain were identified by multiple logistic
      regression analysis. Results: One hundred and ninety patients who had received an
      oxaliplatin-containing regimen via a peripheral venous route were analyzed. None
      of the preventive methods examined significantly reduced the incidence of
      vascular pain. BMI (BMI < 22), clinical stage (I-III) and oxaliplatin dosage (130
      mg/m2 versus dose reduction) were identified as independent risk factors for
      development of vascular pain. The incidence of oxaliplatin-induced vascular pain
      was significantly higher in patients who had two or more risk factors.
      Conclusions: BMI, clinical stage and oxaliplatin dosage were identified as
      independent predictive markers for oxaliplatin-induced vascular pain. Existing
      treatments for vascular pain are not effective in reducing its incidence.

PMID- 30094054
TI  - Imported leishmaniasis cases in Cuba (2006-2016): what have we learned.
AB  - Background: Leishmaniasis is a neglected parasitic disease caused by Leishmania
      spp., which is not endemic in Cuba. However, several factors (such as human
      activities, climate changes, and tourism) have led to an increase in the number
      of leishmaniasis cases in all regions, raising diagnosis and surveillance issues.
      We aim to present the retrospective analysis of 16 human cases suspicious of
      leishmaniasis, which were received during 2006-2016 for diagnosis at the
      Department of Parasitology from the Institute of Tropical Medicine Pedro Kouri,
      Cuba. Methods: Clinical samples were collected and analyzed via different
      diagnostic assays, including direct smear, cultivation, histological analysis,
      and molecular analysis. Epidemiology and background of infection, clinical
      features, sex and age from each patient was recorded. Results: From the 16
      suspicious cases, 5 cases were confirmed for Leishmania infection, based on at
      least two positive results using different methods: PCR-based diagnosis [18S rRNA
      (5/5), hsp20 gene (4/5), hsp70 gene (3/5)], histopathology evaluation (2/3),
      parasite cultivation (2/3), or direct smears (2/3). L. braziliensis and L.
      mexicana were identified as the involving species in two cases, according to
      hsp70 PCR-RFLP protocols. Demographic and clinical features, as well as treatment
      and follow up, are described for every case. Conclusions: The combination of
      parasitological and molecular methods allowed proper diagnosis of imported
      leishmaniasis cases in Cuba. The utility and advantages of molecular diagnosis
      assays in non-endemic countries like Cuba are discussed.

PMID- 30094055
TI  - Multidisciplinary rehabilitation treatment is not effective for myalgic
      encephalomyelitis/chronic fatigue syndrome: A review of the FatiGo trial.
AB  - The FatiGo trial concluded that multidisciplinary rehabilitation treatment is
      more effective for chronic fatigue syndrome/myalgic encephalomyelitis in the long
      term than cognitive behaviour therapy and that multidisciplinary rehabilitation
      treatment is more cost-effective for fatigue and cognitive behaviour therapy for
      quality of life. However, FatiGo suffered from a number of serious methodological
      flaws. Moreover, it ignored the results of the activity metre, its only objective
      outcome. This jeopardizes the validity of FatiGo. Its analysis shows that there
      was no statistically significant difference between multidisciplinary
      rehabilitation treatment and cognitive behaviour therapy and neither are (cost
      )effective. FatiGo's claims of efficacy of multidisciplinary rehabilitation
      treatment and cognitive behaviour therapy for chronic fatigue syndrome/myalgic
      encephalomyelitis are misleading and not justified by their results.

PMID- 30094056
TI  - 'It's been a long haul, a big haul, but we've made it': hepatitis C virus
      treatment in post-transplant patients with virus recurrence: An interpretative
      phenomenological analysis.
AB  - The lived experience of both interferon-based and new interferon-free treatments
      in patients with hepatitis C virus remains understudied. To explore their journey
      through hepatitis C virus treatment, we interviewed seven post-transplant
      patients with recurrent hepatitis C virus. Three themes were identified using
      interpretative phenomenological analysis. Participants reported an ongoing sense
      of ontological uncertainty characterized by lack of control over their condition
      and treatment. Furthermore, an apposition of scepticism and hope accompanying
      each stage of hepatitis C virus treatment was described. A staged approach to
      psychological intervention tailored to the needs of the patient and their
      associated 'stage' of hepatitis C virus treatment was recommended.

PMID- 30094058
TI  - Hesitant steps from the artificial skin to organ regeneration.
AB  - This is a historical account of the steps, both serendipitous and rational, that
      led my group of students and colleagues at MIT and Harvard Medical School to
      discover induced organ regeneration. Our research led to methods for growing back
      in adult mammals three heavily injured organs, skin, peripheral nerves and the
      conjunctiva. We conclude that regeneration in adults is induced by a modification
      of normal wound healing.

PMID- 30094057
TI  - Cerebrospinal fluid GAP-43 in early multiple sclerosis.
AB  - Background/Objective: Novel biomarkers identifying and predicting disease
      activity in multiple sclerosis (MS) would be valuable for primary diagnosis and
      as outcome measures for monitoring therapeutic effects in clinical trials. Axonal
      loss is present from the earliest stages of MS and correlates with disability
      measures. Growth-associated protein 43 (GAP-43) is a presynaptic protein with
      induced expression during axonal growth. We hypothesized this protein could serve
      as a biomarker of axonal regeneration capacity in MS. Methods: We developed a
      novel GAP-43 enzyme-linked immunosorbent assay for quantification in
      cerebrospinal fluid (CSF) and measured GAP-43 levels in 71 patients with
      clinically isolated syndrome, 139 MS patients and 51 controls. Results: GAP-43
      concentrations were similar in patients and controls. Nevertheless, GAP-43 levels
      were higher in patients with >10 T2-magnetic resonance imaging (MRI) lesions (p =
      0.005). CSF GAP-43 concentrations correlated with CSF mononuclear cell counts (p
      = 0.031) and were inversely correlated with patient age (p = 0.038) with a trend
      for higher CSF GAP-43 concentrations in patients with gadolinium-enhancing MRI
      lesions and positive CSF oligoclonal immunoglobulin G status. Conclusion: Our
      results suggest that axonal regeneration capacity is relatively preserved in
      early MS. CSF GAP-43 concentration is positively associated with markers of
      inflammation, suggesting possible inflammatory-driven expression of this growth
      associated protein in early MS.

PMID- 30094060
TI  - Tissue engineering using 3D printed nano-bioactive glass loaded with NELL1 gene
      for repairing alveolar bone defects.
AB  - The purposes of this study were to construct a novel tissue engineered bone
      composed of 3D-printed bioactive glass block/chitosan nanoparticles (BD/CSn)
      composites loaded with Nel-like Type I molecular-1 DNA (pDNA-NELL1) and/or bone
      marrow mesenchymal stem cells (BMSCs), and study their osteogenic activities by
      repairing bone defects in rhesus monkeys. CSn with NELL1 gene plasmid and rhesus
      monkey BMSCs were composited with a BD scaffold to prepare the tissue-engineered
      bone. Four adult female rhesus monkeys with 10- to 12-years old and 5-7 kg in
      weight were used in animal experiments. The first and second premolar teeth from
      four regions of each monkey were removed to form bone defects with size of 10 *
      10 * 5 mm, which were then implanted with above-mentioned tissue engineered bone.
      At 12 weeks after the implantation, gross observations, X-ray and micro-CT
      observations revealed that the new bone was extremely close to normal bone in
      mass, density, hardness, and structure. The bony cortex was smooth and closely
      connected to the surrounding normal bone. Histological observations revealed
      moderate inflammation in the repair area, and the new bone tissues were similar
      to normal ones. In conclusion, tissue engineered bone of this study exhibited
      good osteoconductivity for promoting the formation of new alveolar bone tissue,
      and NELL1 gene played a promotional role in bone regeneration.

PMID- 30094059
TI  - Bone tissue engineering via growth factor delivery: from scaffolds to complex
      matrices.
AB  - In recent years, bone tissue engineering has emerged as a promising solution to
      the limitations of current gold standard treatment options for bone related
      disorders such as bone grafts. Bone tissue engineering provides a scaffold design
      that mimics the extracellular matrix, providing an architecture that guides the
      natural bone regeneration process. During this period, a new generation of bone
      tissue engineering scaffolds has been designed and characterized that explores
      the incorporation of signaling molecules in order to enhance cell recruitment and
      ingress into the scaffold, as well as osteogenic differentiation and
      angiogenesis, each of which is crucial to successful bone regeneration. Here, we
      outline and critically analyze key characteristics of successful bone tissue
      engineering scaffolds. We also explore candidate materials used to fabricate
      these scaffolds. Different growth factors involved in the highly coordinated
      process of bone repair are discussed, and the key requirements of a growth factor
      delivery system are described. Finally, we concentrate on an analysis of scaffold
      based growth factor delivery strategies found in the recent literature. In
      particular, the incorporation of two-phase systems consisting of growth factor
      loaded nanoparticles embedded into scaffolds shows great promise, both by
      providing sustained release over a therapeutically relevant timeframe and the
      potential to sequentially deliver multiple growth factors.

PMID- 30094061
TI  - Application of osteoinductive calcium phosphate ceramics in children's endoscopic
      neurosurgery: report of five cases.
AB  - This work aimed at investigating the possibility and effectiveness of
      osteoinductive calcium phosphate (CaP) ceramics to close the drilled skull holes
      and prevent the postoperative cerebrospinal fluid (CSF) leaking in children's
      endoscopic neurosurgery. Five children patients (four boys and one girl, 3- to 8
      years old) underwent the surgery, in which the endoscopic third ventriculostomy
      (ETV) was operated in four cases of hydrocephalus, and biopsy and ETV were both
      performed in one case of pineal tumor. The drilled skull holes were filled with
      the commercial osteoinductive CaP ceramics. The patients were followed up by CT
      scan at 1, 7 days, 3 and 6 months postoperatively. All the five cases were
      successful, and the holes were closed well after filled with the ceramics. The
      follow-up survey showed that no CSF leaking or rejection reaction was found. The
      CT scan indicated that the drilled holes began healing at 7 days postoperatively,
      and a relatively complete healing happened at 6 months postoperatively. The
      excellent ability of the CaP ceramics to induce bone regeneration was also
      confirmed by repairing the skull defects in a monkey model. The results of MU-CT
      and histological analysis showed that a bony structure with irregular array
      occurred at the defect area, and the newly formed bone volume density reached
      65.7%. In conclusion, the osteoinductive CaP ceramics could be an ideal material
      to treat the drilled skull holes in children's endoscopic neurosurgery and
      prevent CSF leaking afterwards. However, further investigation with more cases
      and longer follow-up was required to evaluate the clinical effect.

PMID- 30094062
TI  - Incorporation of silica nanoparticles to PLGA electrospun fibers for osteogenic
      differentiation of human osteoblast-like cells.
AB  - The development of bone tissue engineering scaffolds still remains a challenging
      field, although various biomaterials have been developed for this purpose.
      Electrospinning is a promising approach to fabricate nanofibers with an
      interconnected porous structure, which can support cell adhesion, guide cell
      proliferation and regulate cell differentiation. The aim of this study is to
      fabricate composite fibers composed of poly(lactic-co-glycolic acid) (PLGA) and
      silica nanoparticles (NPs) via electrospinning and investigate the effect of
      PLGA/SiO2 composite fibers on the cellular response of osteoblast-like cells
      (SaOS-2 cells). SEM and EDX analysis showed that silica NPs were homogenously
      dispersed in the composite fibers. The mechanical behavior of the fibers showed
      that silica NPs acted as reinforcements at concentrations of 2.5 and 5 mg/ml. The
      incorporation of silica NPs led to enhancement of cell attachment and spreading
      on PLGA/SiO2 composite fibers. SaOS-2 cells cultured on PLGA/SiO2 composite
      fibers exhibited increased alkaline phosphatase activity, collagen secretion and
      bone nodules formation. The bone nodules formation of SaOS-2 cells increased
      along with the amount of incorporated silica NPs. The present findings indicate
      that PLGA/SiO2 composite fibers can stimulate osteogenic differentiation of SaOS
      2 cells and may be a promising candidate scaffold for bone tissue engineering.

PMID- 30094063
TI  - Construction and evaluation of fibrillar composite hydrogel of collagen/konjac
      glucomannan for potential biomedical applications.
AB  - Konjac glucomannan (KGM) is recognized as a safe material for its health
      promoting benefits and thus widely used in various fields including
      pharmaceutical industry. In recent decades, the combination of collagen and KGM
      attracts more attentions for biomedical purpose, especially the hybrid films of
      collagen-KGM or collagen-KGM-polysaccharide. In this study, to further and deeply
      develop the intrinsic values of both collagen and KGM as biomaterials, a novel
      kind of composite hydrogel comprising collagen and KGM at a certain ratio was
      fabricated under mild conditions via fibrillogenesis process of the aqueous
      blends of collagen and KGM that experienced deacetylation simultaneously. The
      chemical composition, microcosmic architectures, swelling behavior,
      biodegradation and dynamic mechanic properties of such resulted composite
      hydrogels were systematically investigated. Biologic experiments, including cell
      culture in vitro and hypodermic implantation in vivo, were also conducted on
      these collagen/KGM composite hydrogels to evaluate their biologic performances.
      The relevant results prove that, based on collagen self-assembly behavior, this
      synthesis strategy is efficient to construct a composite hydrogel of collagen/KGM
      with improved mechanical properties, biodegradability, excellent biocompatibility
      and bioactivity, which are promising for potential biomedical applications such
      as tissue engineering and regenerative medicine.

PMID- 30094065
TI  - Low-dose nivolumab can be effective in non-small cell lung cancer: alternative
      option for financial toxicity.
AB  - Objectives: Nivolumab is used at 3 mg/kg or fixed doses of 240 mg every 2 weeks.
      There was no dose-response/toxicity relationship of nivolumab. This study
      evaluated the efficacy of low-dose nivolumab as an alternative to the financial
      toxicity of standard-dose nivolumab in treatment of non-small cell lung cancer
      (NSCLC). Methods: Outcomes of patients with NSCLC treated with nivolumab as a
      routine practice at two tertiary hospitals in Korea were retrospectively
      analysed. Patients who could not afford standard nivolumab treatment received low
      dose nivolumab (20 or 100 mg fixed dose every 3 weeks). Others received standard
      dose of 3 mg/kg every 2 weeks. Progression-free survival (PFS) and overall
      survival (OS) were measured and compared between low-dose and standard-dose
      groups in overall and stratified analyses according to programmed death-ligand 1
      (PD-L1) status. Results: Among the 47 patients with NSCLC, 18 received low-dose
      nivolumab. PD-L1 positivity was observed in 13 (27.7%) patients and did not
      differ between the groups. During 5.2 months of follow-up, the objective response
      rate was 13.8% in the standard-dose group and 16.7% in the low-dose group
      (p=0.788). Dosing of nivolumab or PD-L1 expression did not significantly affect
      PFS or OS. Conclusion: Low-dose nivolumab can be effective in NSCLC and is worth
      considering as an alternative option to reducing financial toxicity. The efficacy
      of low-dose nivolumab requires study.

PMID- 30094066
TI  - High incidence of cetuximab-related infusion reactions in head and neck patients.
AB  - Background: Cetuximab is crucial in the management of squamous cell carcinoma of
      the head and neck of patients. Grade 3-4 cetuximab-induced infusion reactions (CI
      IRs) occur in 2% of patients with colorectal cancer. Despite the 2.7% CI-IR rate
      in the EXTREME trial, higher rates were reported in small series of patients with
      head and neck squamous cell carcinoma (HNSCC) (6%-18%). There is an urgent need
      to better appraise the natural history and the predictive factors for CI-IRs in
      patients with HNSCC exposed to cetuximab. Methods: The medical records from
      patients with HNSCC (n=428) treated by cetuximab at Gustave Roussy from January
      2013 to December 2015 were reviewed. The impact of potential risk factors was
      analysed. Results: Out of 428 patients, 24 patients (5.4%) presented CI-IR,
      including grade 3-4 (95.7%); about 21% (5/24) requiring intensive care unit
      referral and quasi all occurred within the first cycle (21/24). In a multivariate
      analysis, the occurrence of grade 3-4 CI-IR was associated with tobacco and
      alcohol history (p=8.5e-3) and with prior allergy history (p=2.9e-3). CI-IRs
      tended to be associated with poor overall survival in patients with recurrent and
      metastatic HNSCC and with a higher number of further lines of chemotherapy.
      Conclusion: In real life, CI-IRs appear far more common in patients with HNSCC
      (5.4%) than reported in prospective trials. This is the largest series of
      patients ever focusing on the risk of CI-IR in patients with HNSCC. Prior allergy
      history and tobacco history are associated with CI-IR and could be used to better
      allocate treatment. Further prospective data are required to confirm these
      findings.

PMID- 30094064
TI  - Comparative genetic and genomic analysis of the novel fusellovirus Sulfolobus
      spindle-shaped virus 10.
AB  - Viruses that infect thermophilic Archaea are unique in both their structure and
      genetic makeup. The lemon-shaped fuselloviruses-which infect members of the order
      Sulfolobales, growing optimally at 80  degrees C and pH 3-are some of the most
      ubiquitous and best studied viruses of the thermoacidophilic Archaea.
      Nonetheless, much remains to be learned about these viruses. In order to
      investigate fusellovirus evolution, we have isolated and characterized a novel
      fusellovirus, Sulfolobus spindle-shaped virus 10 (formerly SSV-L1). Comparative
      genomic analyses highlight significant similarity with both SSV8 and SSV9, as
      well as conservation of promoter elements within the Fuselloviridae. SSV10
      encodes five ORFs with no homology within or outside of the Fuselloviridae, as
      well as a putatively functional Cas4-like ORF, which may play a role in evading
      CRISPR-mediated host defenses. Moreover, we demonstrate the ability of SSV10 to
      withstand mutation in a fashion consistent with mutagenesis in SSV1.

PMID- 30094067
TI  - CSF-1 and Ang-2 serum levels - prognostic and diagnostic partners in non-small
      cell lung cancer.
AB  - Background: Lung cancer is the most incident and lethal form of cancer, with late
      diagnosis as a major determinant of its bad prognosis. Immunotherapies targeting
      immune checkpoints improve survival, but positive results encompass only 30%-40%
      of the patients, possibly due to alternative pathways to immunosuppression,
      including tumour-associated macrophages (TAM). Colony stimulating factor-1 (CSF
      1) is implicated in TAM differentiation and recruitment to tumours and in tumour
      angiogenesis, through a special setting of Tie-2-expressing macrophages, which
      respond to angiopoietin-2 (Ang-2). We evaluated the role of serum levels of CSF-1
      in non-small cell lung cancer (NSCLC) prognosis and whether these could serve as
      biomarkers for NSCLC detection, along with Ang-2. Participants and methods: We
      prospectively studied an unselected cohort of 145 patients with NSCLC and a group
      of 30 control individuals. Serum levels of Ang-2 and CSF-1 were measured by ELISA
      prior to treatment. Results: Serum levels of CSF-1 and Ang-2 are positively
      correlated (p<0.000001). Individuals with high serum levels of CSF-1 have a 17
      fold risk for NSCLC presence and patients with combined High Ang-2/CSF-1 serum
      levels present a 5-fold increased risk of having NSCLC. High Ang-2/CSF-1
      phenotype is also associated with worst prognosis in NSCLC. Conclusions: Combined
      expression of CSF-1 and Ang-2 seems to contribute to worst prognosis in NSCLC and
      it is worthy to understand the basis of this unexplored partnership. Moreover, we
      think CSF-1 could be included as a biomarker in NSCLC screening protocols that
      can improve the positive predictive value of the current screening modalities,
      increase overall cost effectiveness and potentially improve lung cancer survival.

PMID- 30094069
TI  - PHOTOSTENT-02: porfimer sodium photodynamic therapy plus stenting versus stenting
      alone in patients with locally advanced or metastatic biliary tract cancer.
AB  - Background: Endobiliary stenting is standard practice for palliation of
      obstructive jaundice due to biliary tract cancer (BTC). Photodynamic therapy
      (PDT) may also improve biliary drainage and previous small studies suggested
      survival benefit. Aims: To assess the difference in outcome between patients with
      BTC undergoing palliative stenting plus PDT versus stenting alone. Methods: 92
      patients with confirmed locally advanced or metastatic BTC, ECOG performance
      status 0-3 and adequate biliary drainage were randomised (46 per group) to
      receive porfimer sodium PDT plus stenting or stenting alone. The primary end
      point was overall survival (OS). Toxicity and progression-free survival (PFS)
      were secondary end points. Treatment arms were well balanced for baseline factors
      and prior therapy. Results: No significant differences in grade 3-4 toxicities
      and no grade 3-4 adverse events due to PDT were observed. Thirteen (28%) PDT
      patients and 24 (52%) stent alone patients received subsequent palliative
      chemotherapy. After a median follow-up of 8.4 months, OS and PFS were worse in
      patients receiving PDT compared with stent alone group (OS median 6.2 vs 9.8
      months (HR 1.56, 95% CI 1.00 to 2.43, p=0.048) and PFS median 3.4 vs 4.3 months
      (HR 1.43, 95% CI: 0.93 to 2.18, p=0.10), respectively). Conclusion: In patients
      with locally advanced or metastatic BTC, PDT was associated with worse outcome
      than stenting alone, explained only in part by the differences in chemotherapy
      treatments. We conclude that optimal stenting remains the treatment of choice for
      malignant biliary obstruction and the use of PDT for this indication cannot be
      recommended outside of clinical trials. Trial registration number: ISRCTN
      87712758; EudraCT 2005-001173-96; UKCRN ID: 1461.

PMID- 30094068
TI  - Real-world features associated with cancer-related venous thromboembolic events.
AB  - Background: The incidence of venous thromboembolism (VTE) is 1-2/1000
      individuals. Patients with cancer, especially during chemotherapy, are at
      enhanced risk, but real-world data on factors associated with VTE events are
      still scarce. Aim: The aim of this retrospective study was to survey the
      incidence of VTE based on a large hospital database, and to identify
      comorbidities and features associated with VTE events. We focused on cancer
      related VTE events and on factors indicating increased VTE risk during
      chemotherapy. Methods: The cohort included patients treated at Turku University
      Hospital during years 2005-2013. Health information was derived and analysed from
      multiple electronic databases. The diagnoses of VTE and all comorbidities,
      including type of cancer, were based on International Classification of Diseases
      10th Revision coding. For further analysis, we focused on 16 common types of
      cancers treated with chemotherapy. Age, gender, surgery, radiotherapy, distant
      metastasis, available laboratory values and platinum-based chemotherapy were
      evaluated for VTE group, and associations were estimated by Cox regression
      analyses. Results: The entire database contained information from 495 089
      patients, of whom 5452 (1.1%) had a VTE diagnosis. Among individuals with VTE,
      1437 (26.4%) had diagnosis of coronary heart disease and 1467 (26.9%) had cancer
      diagnosis. Among 7778 patients with cancer treated with chemotherapy, 282 (3.6%)
      had a VTE, platinum-based chemotherapy being a major risk factor (HR 1.77, 95% CI
      1.40 to 2.24, p<0.001). In multivariate analysis, elevated blood neutrophil
      counts (>3.25*109 cells/L, HR 1.96, 95% CI 1.33 to 2.89, p<0.001) and plasma
      creatinine (>62.5 MUmol/L; HR 1.60, 95% CI 1.21 to 2.13, p=0.001) values were
      independent indicators of increased VTE risk during chemotherapy. Conclusions:
      Longitudinal electronic health record analysis provides a powerful tool to gather
      meaningful real-world information to study clinical associations, like
      comorbidities, and to identify markers associated with VTE. The combination of
      various clinical and laboratory variables could be used for VTE risk evaluation
      and targeted prevention.

PMID- 30094071
TI  - Challenge of implementing clinical practice guidelines. Getting ESMO's guidelines
      even closer to the bedside: introducing the ESMO Practising Oncologists'
      checklists and knowledge and practice questions.

PMID- 30094072
TI  - Benefit of adjuvant chemotherapy based on lymph node involvement for oesophageal
      cancer following trimodality therapy.
AB  - Background: Oesophageal cancer (OC) survival rates have improved since the
      widespread adoption of neoadjuvant chemoradiation therapy (NACRT) followed by
      oesophagectomy (trimodality therapy). Unfortunately, the overall prognosis for
      patients with locally advanced disease remains poor. In this study, we sought to
      assess the effect of adjuvant chemotherapy (AC) in patients treated with
      trimodality therapy. Methods: Using the National Cancer Database we
      retrospectively identified 6785 patients with locally advanced (cT1b-T4a, N0-N+,
      M0) OC who were treated with trimodality therapy from 2006 to 2014. Patients were
      separated based on receipt of AC (n=463), as well as clinical and pathological
      lymph node involvement. Overall survival (OS) between groups was compared using
      the Kaplan-Meier method and Cox proportional hazard modelling. Results: Based on
      multivariate analysis, AC was associated with a statistically significantly
      reduced risk of death (HR 0.77, p<0.001). Subgroup analysis revealed that AC was
      associated with reduced risk of death compared with NACRT alone in the cN+/pN0
      (median OS 64 vs 43 months; p=0.019) and the cN+/pN+ (median OS 27 vs 22 months;
      p=0.010) groups, but not in the cN0/pN0 (median OS 48 vs 49 months; p=0.253) or
      cN0/pN+ (median OS 31 vs 24 months; p=0.077) groups. Conclusion: AC following
      trimodality therapy may improve survival in patients with locally advanced OC.
      Patients who undergo lymph node downstaging may be the most likely to benefit
      from AC. Prospective studies are needed to confirm this finding.

PMID- 30094070
TI  - Association of homogeneous inflamed gene signature with a better outcome in
      patients with metastatic melanoma treated with MAGE-A3 immunotherapeutic.
AB  - Purpose: This study assessed clinical activity, safety and immunogenicity of MAGE
      A3 immunotherapeutic in patients with MAGE-A3-positive metastatic melanoma.
      Patients and methods: In this open-label, multicentre, uncontrolled, Phase II
      study (ClinicalTrials.gov NCT00896480), patients received <=24 doses of MAGE-A3
      immunotherapeutic (4-cycle schedule). At screening, two skin lesions were
      biopsied for MAGE-A3 expression analysis and presence/absence of a previously
      identified gene signature (GS) associated with favourable clinical outcome.
      Clinical activity was assessed in terms of clinical response, time-to-treatment
      failure (TTF) and progression-free survival (PFS). Adverse events (AEs) and
      serious AEs (SAEs) were recorded. MAGE-A3-specific immune responses were
      assessed. Clinical activity and immunogenicity were analysed overall and
      separately in patients with 2/2 (GS+/+), 1/2 (GS+/-) or 0/2 (GS-/-) biopsies
      presenting GS. Results: Of 49 screened patients, 32 had MAGE-A3-positive tumours;
      24 (8 GS+/+, 8 GS+/-, 8 GS-/-) were treated. Two complete (GS+/+ patients) and
      two partial responses (one GS+/+, one GS+/-) were reported; of note, one of the
      two complete responses was unlikely to be related to the study treatment. Median
      TTF and PFS were 14.8 and 7.2 months for GS+/+, 2.3 and 2.8 months for GS+/- and
      2.4 and 2.9 months for GS-/- patients. Three grade 3 AEs and two SAEs unrelated
      to treatment were reported. All patients were seropositive for MAGE-A3 antibodies
      on vaccination with no differences between the different GS profiles. MAGE-A3
      specific CD4+ and CD8+ T cell immunogenicity was detected; 12/16 (75.0%) of
      patients presented CD4+ T cell responses. Conclusion: Treatment with MAGE-A3
      immunotherapeutic showed signs of clinical activity in GS+/+ patients. Treatment
      was well tolerated and immunogenic. No differences in immune responses according
      to GS status were observed. Trial registration number: NCT00896480 (Results).

PMID- 30094073
TI  - Phase I, open-label study of pasireotide in patients with BRAF-wild type and NRAS
      wild type, unresectable and/or metastatic melanoma.
AB  - Introduction: Somatostatin analogues exert antitumour activity via direct and
      indirect mechanisms. The present study was designed to assess the safety and
      efficacy of pasireotide in patients with BRAF-wild type (WT) and NRAS-WT
      metastatic melanoma. Patients and methods: Patients with unresectable and/or
      metastatic melanoma or Merkel cell carcinoma were eligible. Pasireotide was
      administered at different doses for <=8 weeks in dose-escalation phase, followed
      by long-acting pasireotide 80 mg or lower dose in case of toxicity in follow-up
      phase up to six additional months. Primary endpoint was safety in the first 8
      weeks of dose-escalation phase. Results: The study was terminated early due to
      slow recruitment. Of the 10 patients with metastatic melanoma enrolled, only four
      reached the high dose level: two patients reached 3600 ug in dose-escalation and
      follow-up phases and two patients reached 3600 ug in dose-escalation and long
      acting pasireotide 80 mg in follow-up phases and were stable for >5 months. Most
      common adverse events (AEs) during dose-escalation phase in >=2 patients (20%)
      were: diarrhoea (50%), nausea (50%), fatigue (20%), hyperglycaemia (20%),
      hypophosphatemia (20%), chills (20%) and tumour pain (20%). Grade 3 or 4 study
      drug-related AEs were diarrhoea and nausea, reported in one patient. Partial
      response was documented in one patient and stable disease in another.
      Conclusions: Pasireotide was well tolerated, and safety results were similar to
      those previously reported in other indications. Further studies are needed to
      evaluate its antitumour activity alone and in combination with other drugs in
      melanoma.

PMID- 30094074
TI  - Phase II study assessing the benefit of cisplatin re-introduction (stop-and-go
      strategy) in patients with advanced non-squamous non-small cell lung cancer: the
      IFCT-1102 BUCiL study (a Better Use of Cisplatin in Lung cancer).
AB  - Introduction: This single-arm phase II trial aimed to evaluate a stop-and-go
      strategy with cisplatin-based chemotherapy and bevacizumab in advanced non
      squamous non-small cell lung cancer (NSCLC). Methods: Patients were initially
      treated with three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 1)
      followed by bevacizumab maintenance and after progression, re-introduction of
      three cycles of pemetrexed, cisplatin plus bevacizumab (sequence 2) and
      pemetrexed plus bevacizumab maintenance. The primary endpoint was the proportion
      of patients with advanced non-squamous NSCLC receiving the complete sequence 2
      without platinum dose reduction (hypothesis >=75%). Results: 120 patients with
      performance status <=1 were included. Of 113 patients evaluable for efficacy, 65
      (57.5%) entered in sequence 2 and 56 (86%) received the three planned cycles
      including 37 (56.9%, 95% CI 45.1 to 73.6) without platinum dose reduction. The
      median progression-free survival 1 (PFS1; inclusion to progression 1) was 5.6
      months (95% CI 5.0 to 6.3) and median PFS2 (progression 1 to progression 2) was
      6.8 months (95% CI 5.8 to 8.8). The median disease control duration (PFS1+PFS2;
      n=65) was 12.4 months (95% CI 11.2 to 14.9). The median overall survival was 17.7
      months (95% CI 13.1 to 21.6) and 20.5 months (95% CI 16.9 to 26.9) for patients
      reaching the sequence 2 (n=65). Conclusion: Although the stringent primary
      endpoint was not met, this stop-and-go strategy with platinum-based chemotherapy
      plus bevacizumab continuation beyond progression compares favourably with
      standard schedule, deserving to be further studied in advanced non-squamous
      NSCLC.

PMID- 30094076
TI  - Patient-reported outcomes in a phase II study of alectinib.

PMID- 30094077
TI  - Editorial: Special Issue: Biotechnological and medical relevance of ureases.

PMID- 30094075
TI  - Multidisciplinary molecular tumour board: a tool to improve clinical practice and
      selection accrual for clinical trials in patients with cancer.
AB  - Background: The complexity of delivering precision medicine to oncology patients
      has led to the creation of molecular tumourboards (MTBs) for patient selection
      and assessment of treatment options. New technologies like the liquid biopsy are
      augmenting available therapeutic opportunities. This report aims to analyse the
      experience of our MTB in the implementation of personalised medicine in a cancer
      network. Materials and methods: Patients diagnosed with solid tumours progressing
      to standard treatments were referred to our Phase I unit. They underwent
      comprehensive next generation sequencing (NGS) of either tumour tissue or cell
      free circulating tumour DNA (ctDNA) or both. The MTB expressed either a positive
      or negative opinion for the treatment of the patients with discovered druggable
      alterations inside a clinical trial, in an expanded access programme, with a
      compassionate use. Afterwards, discovered alterations were matched with OncoKB
      levels of evidence for the choice of alteration-specific treatments in order to
      compare MTB outcomes with a standardised set of recommendations. Results: NGS was
      performed either on ctDNA or tumour tissue or in both of them in 204 patients.
      The MTB evaluated 173 of these cases. Overall, the MTB proposed alteration
      specific targeted therapy to 72 patients (41.6%). 49 patients (28.3% of the total
      evaluated) were indicated to enter a clinical trial. In 29 patients with matched
      liquid biopsy NGS (lbNGS), tumour tissue NGS (ttNGS) and MTB evaluation, the MTB
      changed the treatment strategy coming from standardised recommendations based on
      lbNGS and ttNGS alone in 10 patients (34.5%), thanks to the evaluation of other
      clinical parameters. In our cohort, lbNGS was more likely, compared with ttNGS,
      to detect point mutations (OR 11, 95% CI 2.9 to 24.1, p<0.001) and all-type
      alterations (OR 13.6, 95% CI 5.5 to 43.2, p<0.001) from the same genes of matched
      patients. Conclusions: Our MTB allows patients with refractory cancer to be
      included in clinical trials and improves the precision of clinical decisions
      compared with a standardised set of mutation-driven recommendations.

PMID- 30094079
TI  - Agronomic efficiency of NBPT as a urease inhibitor: A review.
AB  - Urea is the most widely used nitrogen (N) fertilizer, with a projected increase
      in annual demand of 1.5% in the coming years. After its application to soil, urea
      undergoes hydrolysis via the urease enzyme, causing increases in the soil pH in
      the surrounding area of the granules and resulting in NH3 losses that average 16%
      of N applied worldwide and can reach 40% or more in hot and humid conditions. The
      use of urease inhibitors is an effective way to reduce NH3 losses. Several
      compounds act as urease inhibitors, but only N-(n-butyl) thiophosphoric triamide
      (NBPT) has been used worldwide, being the most successful in a market that has
      grown 16% per year in the past 10 years. Only in the past three years other
      compounds are being commercially launched. In comparison to urea, NBPT-treated
      urea reduces NH3 loss by around 53%. Yield gain by NBPT usage is of the order of
      6.0% and varies from -0.8 to 10.2% depending on crop species. Nitrification
      inhibitors usually increase NH3 volatilization and mixing them with urease
      inhibitors partially offsets the benefits of the latter in reducing NH3 loss. The
      efficacy of NBPT to reduce NH3 loss is well documented, but there is a need for
      further improvement to increase the period of inhibition and the shelf life of
      NBPT-treated urea.

PMID- 30094080
TI  - A minireview on what we have learned about urease inhibitors of agricultural
      interest since mid-2000s.
AB  - World population is expected to reach 9.7 billion by 2050, which makes a great
      challenge the achievement of food security. The use of urease inhibitors in
      agricultural practices has long been explored as one of the strategies to
      guarantee food supply in enough amounts. This is due to the fact that urea, one
      of the most used nitrogen (N) fertilizers worldwide, rapidly undergoes urease
      driven hydrolysis on soil surface yielding up to 70% N losses to environment.
      This review provides with a compilation of what has been done since 2005 with
      respect to the search for good urease inhibitors of agricultural interests. The
      potential of synthetic organic molecules, such as phosphoramidates, hydroquinone,
      quinones, (di)substituted thioureas, benzothiazoles, coumarin and phenolic
      aldehyde derivatives, and vanadium-hydrazine complexes, together with B, Cu, S,
      Zn, ammonium thiosulfate, silver nanoparticles, and oxidized charcoal as urease
      inhibitors was presented from experiments with purified jack bean urease,
      different soils and/or plant-soil systems. The ability of some urease inhibitors
      to mitigate formation of greenhouse gases is also discussed.

PMID- 30094081
TI  - Ureases in the gastrointestinal tracts of ruminant and monogastric animals and
      their implication in urea-N/ammonia metabolism: A review.
AB  - Urea in diets of ruminants has been investigated to substitute expensive animal
      and vegetable protein sources for more than a century, and has been widely
      incorporated in diets of ruminants for many years. Urea is also recycled to the
      fermentative parts of the gastrointestinal (GI) tracts through saliva or direct
      secretory flux from blood depending upon the dietary situations. Within the GI
      tracts, urea is hydrolyzed to ammonia by urease enzymes produced by GI
      microorganisms and subsequent ammonia utilization serves the synthesis of
      microbial protein. In ruminants, excessive urease activity in the rumen may lead
      to urea/ammonia toxicity when high amounts of urea are fed to animals; and in non
      ruminants, ammonia concentrations in the GI content and milieu may cause damage
      to the GI mucosa, resulting in impaired nutrient absorption, futile energy and
      protein spillage and decreased growth performance. Relatively little attention
      has been directed to this area by researchers. Therefore, the present review
      intends to discuss current knowledge in ureolytic bacterial populations, urease
      activities and factors affecting them, urea metabolism by microorganisms, and the
      application of inhibitors of urease activity in livestock animals. The
      information related to the ureolytic bacteria and urease activity could be useful
      for improving protein utilization efficiency in ruminants and for the reduction
      of the ammonia concentration in GI tracts of monogastric animals. Application of
      recent molecular methods can be expected to provide rationales for improved
      strategies to modulate urease and urea dynamics in the GI tract. This would lead
      to improved GI health, production performance and environmental compatibility of
      livestock production.

PMID- 30094082
TI  - Helicobacter pylori urease for diagnosis of Helicobacter pylori infection: A mini
      review.
AB  - The stomach contents contain of both acid and proteolytic enzymes. How the
      stomach digests food without damaging itself remained a topic of investigation
      for decades. One candidate was gastric urease, which neutralized acid by
      producing ammonia from urea diffusing from the blood and potentially could
      protect the stomach. Discovery that gastric urease was not mammalian resulted in
      a research hiatus until discovery that gastric urease was produce by Helicobacter
      pylori which caused gastritis, peptic ulcer and gastric cancer. Gastric urease
      allows the organism to colonize the acidic stomach and serves as a biomarker for
      the presence of H. pylori. Important clinical tests for H. pylori, the rapid
      urease test and urea breath test, are based on gastric urease. Rapid urease tests
      use gastric biopsies or mucus placed in a device containing urea and an indicator
      of pH change, typically phenol red. Urea breath tests measure the change in
      isotope enrichment of 13C- or 14CO2 in breath following oral administration of
      labeled urea. The urea breath test is non-invasive, convenient and accurate and
      the most widely used test for non-invasive test for detection of active H. pylori
      infection and for confirmation of cure after eradication therapy.

PMID- 30094078
TI  - Ureases: Historical aspects, catalytic, and non-catalytic properties - A review.
AB  - Urease (urea amidohydrolase, EC 3.5.1.5) is a nickel-containing enzyme produced
      by plants, fungi, and bacteria that catalyzes the hydrolysis of urea into ammonia
      and carbamate. Urease is of historical importance in Biochemistry as it was the
      first enzyme ever to be crystallized (1926). Finding nickel in urease's active
      site (1975) was the first indication of a biological role for this metal. In this
      review, historical and structural features, kinetics aspects, activation of the
      metallocenter and inhibitors of the urea hydrolyzing activity of ureases are
      discussed. The review also deals with the non-enzymatic biological properties,
      whose discovery 40 years ago started a new chapter in the study of ureases. Well
      recognized as virulence factors due to the production of ammonia and
      alkalinization in diseases by urease-positive microorganisms, ureases have pro
      inflammatory, endocytosis-inducing and neurotoxic activities that do not require
      ureolysis. Particularly relevant in plants, ureases exert insecticidal and
      fungitoxic effects. Data on the jack bean urease and on jaburetox, a recombinant
      urease-derived peptide, have indicated that interactions with cell membrane
      lipids may be the basis of the non-enzymatic biological properties of ureases.
      Altogether, with this review we wanted to invite the readers to take a second
      look at ureases, very versatile proteins that happen also to catalyze the
      breakdown of urea into ammonia and carbamate.

PMID- 30094083
TI  - Urease-aided calcium carbonate mineralization for engineering applications: A
      review.
AB  - Inducing calcium carbonate precipitation is another important function of urease
      in nature. The process takes advantage of the supply of carbonate ions derived
      from urea hydrolysis and of an increase in pH generated by the reaction, effects
      that in the presence of Ca2+ ions lead to the precipitation of CaCO3. Further to
      its importance in nature, if performed in a biomimetic manner, the urease-aided
      CaCO3 mineralization offers enormous potential in innovative engineering
      applications as an eco-friendly technique operative under mild conditions, to be
      used for remediation and cementation/deposition in field applications in situ.
      These include among others, the strengthening and consolidation of soil/sand, the
      protection and restoration of stone and concrete structures, conservation of
      stone cultural heritage materials, cleaning waste- and groundwater of toxic
      metals and radionuclides, and plugging geological formations for the enhancement
      of oil recovery and geologic CO2 sequestration. In view of the potential of this
      newly emerging interdisciplinary branch of engineering, this article presents the
      principles of urease-aided calcium carbonate mineralization apposed to other
      biomineralization processes, and reviews the advantages and limitations of the
      technique compared to the conventional techniques presently in use. Further, it
      presents areas of its existing and potential applications, notably in
      geotechnical, construction and environmental engineering, and its future
      perspectives.

PMID- 30094085
TI  - Recent advances in design of new urease inhibitors: A review.
AB  - Urease is a nickel-dependent metalloenzyme found in plants, some bacteria, and
      fungi. Bacterial enzyme is of special importance since it has been demonstrated
      as a potent virulence factor for some species. Especially it is central to
      Helicobacter pylori metabolism and virulence being necessary for its colonization
      of the gastric mucosa, and is a potent immunogen that elicits a vigorous immune
      response. Therefore, it is not surprising that efforts to design, synthesize and
      evaluate of new inhibitors of urease are and active field of medicinal chemistry.
      In this paper recent advances on this field are reviewed.

PMID- 30094086
TI  - Schiff bases and their metal complexes as urease inhibitors - A brief review.
AB  - Schiff bases, an aldehyde- or ketone-like compounds in which the carbonyl group
      is replaced by an imine or azomethine, are some of the most widely used organic
      compounds. Indeed, they are widely used for industrial purposes and also exhibit
      a broad range of biological activities, including anti-urease activity. Ureases,
      enzymes that catalyze urea hydrolysis, have received considerable attention for
      their impact on living organisms' health, since the persistence of urease
      activity in human and animal cells can be the cause of some diseases and pathogen
      infections. This short review compiles examples of the most antiurease Schiff
      bases (0.23 MUM < IC50 < 37.00 MUM) and their metal complexes (0.03 MUM < IC50 <
      100 MUM). Emphasis is given to ureases of Helicobacter pylori and Canavalia
      ensiformis, although the active site of this class of hydrolases is conserved
      among living organisms.

PMID- 30094087
TI  - Food safety impacts of antimicrobial use and their residues in aquaculture.
AB  - Background: Residues of antimicrobials in food have received much attention in
      recent years because of growing food safety and public health concerns. Their
      presence in food of animal origin constitutes socioeconomic challenges in
      international trade in animal and animal products. The major public health
      significances of antimicrobial residues include the development of antimicrobial
      drug resistance, hypersensitivity reaction, carcinogenicity, mutagenicity,
      teratogenicity, bone marrow depression, and disruption of normal intestinal
      flora. Indiscriminate use of antimicrobials in aquaculture resulting in
      occurrence of residues in aquaculture products and associated harmful health
      effects in humans requires control measures to ensure consumer protection. Main
      body: This article focuses on factors contributing to the presence of
      antimicrobial residues in aquaculture products and their implications on
      consumers' safety. Regulatory actions aimed at prudent use of veterinary drugs in
      food-producing animals with emphasis on aquaculture for safe and wholesome food
      production are also reviewed. Conclusion: Prudent use of antibiotics in
      aquaculture under veterinary supervision is critical in ensuring safety of
      aquaculture products. Good animal husbandry practices as well as the use of
      alternatives to antibiotics such as vaccination, probiotics, phage therapy, and
      essential oils are recommended panaceas to reducing the use of antimicrobial
      residues in aquaculture and consequent food safety effects.

PMID- 30094084
TI  - A review on the development of urease inhibitors as antimicrobial agents against
      pathogenic bacteria.
AB  - Ureases are enzymes that hydrolyze urea into ammonium and carbon dioxide. They
      have received considerable attention due to their impacts on living organism
      health, since the urease activity in microorganisms, particularly in bacteria,
      are potential causes and/or factors contributing to the persistence of some
      pathogen infections. This review compiles examples of the most potent antiurease
      organic substances. Emphasis was given to systematic screening studies on the
      inhibitory activity of rationally designed series of compounds with the
      corresponding SAR considerations. Ureases of Canavalia ensiformis, the usual
      model in antiureolytic studies, are emphasized. Although the active site of this
      class of hydrolases is conserved among bacteria and vegetal ureases, the same is
      not observerd for allosteric site. Therefore, inhibitors acting by participating
      in interactions with the allosteric site are more susceptible to a potential lack
      of association among their inhibitory profile for different ureases. The
      information about the inhibitory activity of different classes of compounds can
      be usefull to guide the development of new urease inhibitors that may be used in
      future in small molecular therapy against pathogenic bacteria.

PMID- 30094092
TI  - A novel positive feedback regulation between long noncoding RNA UICC and IL
      6/STAT3 signaling promotes cervical cancer progression.
AB  - Long noncoding RNAs (lncRNAs), a novel class of transcripts that have critical
      roles in carcinogenesis and progression, have emerged as important gene
      expression modulators. However, the pathophysiological contributions and the
      underlying mechanisms of specific lncRNAs in cervical cancer remain largely
      unknown. Here, using transcriptome microarray analysis, we identified a novel
      lncRNA termed lncRNA upregulated in cervical cancer (lnc-UICC) that was highly
      expressed in cervical cancer tissue. lnc-UICC expression in cervical cancer was
      associated with FIGO stage, lymph node metastasis and prognosis. Through gain-
      and loss-of-lnc-UICC expression, we found lnc-UICC could significantly promote
      tumor growth and metastasis in vitro and in vivo. Mechanistically, lnc-UICC
      promoted STAT3 activation through two complementary ways. lnc-UICC could regulate
      the IL-6 transcription through binging to IL-6 promoter. lnc-UICC also directly
      interacted with the phospho-STAT3, and increased its protein stability by
      protecting it from proteasome-dependent degradation. Moreover, we revealed that
      lnc-UICC was a STAT3-responsive lncRNA, as STAT3 could bind to the lnc-UICC
      promoter to enhance its transcription, suggesting that there exists a positive
      feedback loop between lnc-UICC and IL-6/STAT3 signaling. In sum, therefore, we
      have identified an lncRNA-based IL-6/STAT3 signaling regulatory circuit that
      promotes tumorigenesis and metastasis in cervical cancer cells, highlighting the
      role that lncRNAs can play in tumor progression.

PMID- 30094088
TI  - The animal nuclear factor Y: an enigmatic and important heterotrimeric
      transcription factor.
AB  - Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor with the ability
      to bind to CCAAT boxes in nearly all eukaryotes and has long been a topic of
      interest since it is first identified. In plants, due to each subunit of NF-Y is
      encoded by multiple gene families, there are a wide variety NF-Y complex
      combinations that fulfill many pivotal functions. However, the animal NF-Y
      complex usually has only one type of combination, as each subunit is generally
      encoded by a single gene. Even though, mounting evidence points to that the
      animal NF-Y complex is also essential for numerous biological processes involved
      in proliferation and apoptosis, cancer and tumor, stress responses, growth and
      development. Therefore, a relatively comprehensive functional dissection of
      animal NF-Y will enable a deeper comprehension of how lesser combinations of the
      NF-Y complex regulate diverse aspects of biology processes in animal. Here, we
      focus mainly on reviewing recent advances related to NF-Y in the animal field,
      including subunit structural characteristics, expression regulation models and
      biological functions, and we also discuss future directions.

PMID- 30094090
TI  - Circular RNAs in digestive system cancer: potential biomarkers and therapeutic
      targets.
AB  - Circular RNAs (circRNAs) are a series of special closed circular RNA molecules
      with stability and conservatism. In recent years, advances in high-throughput RNA
      sequencing technology have led to explosive discovery of circRNAs in different
      types of species and cells. Moreover, circRNAs can accomplish a remarkable
      multitude of biological functions, such as regulating transcription or splicing,
      serving as miRNA sponges, interacting with RNA-binding proteins, and translating
      proteins. Meanwhile, circRNAs involve in the biogenesis and development of many
      diseases, including cardiovascular disorders, nervous system disorders, cancers,
      etc. Herein, we discuss the latest research progress of circRNA, as well as their
      diagnostic and prognostic significance in digestive system cancers. In addition,
      this paper highlights that circRNAs might serve as potential therapeutic targets
      for novel drugs by taking digestive system cancer as an illustrative example.

PMID- 30094093
TI  - A deficiency in cathelicidin reduces lung tumor growth in NNK/NTHi-induced A/J
      mice.
AB  - Cathelicidin is an antimicrobial peptide that plays an essential role in cell
      proliferation, angiogenesis, and also has been indicated in tumor promotion.
      However, it is unclear how cathelicidin causes tumor growth, and the pathogenic
      mechanisms based on gain or loss of function have not been proposed. Here, a
      cathelicidin related antimicrobial peptide (CRAMP) knockout mouse was generated
      using an A/J background (A/J-CRAMP-/- mice), and lung carcinoma growth was
      induced using 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and Non
      typeable Haemophilus influenzae (NTHi). Compared with A/J mice, A/J-CRAMP-/- mice
      were found to have a lower tumor burden and longer survival times, with a
      significant reduction in both PCNA and Ki-67 positive cells. However, there was
      no difference between the number of apoptotic lung-cancer cells between the A/J
      and A/J-CRAMP-/- mice. This indicated cathelicidin might be a tumor growth factor
      for lung cancer, which was associated for proliferation of tumor cells. In the
      future, this animal model will be useful to study the distinct role of
      cathelicidin in induced-lung cancer development.

PMID- 30094089
TI  - MicroRNA regulation of liver cancer stem cells.
AB  - MicroRNAs (miRNAs), a class of emerging small non-coding RNAs, serve as vital
      players in modulating multiple biological processes via the post-transcriptional
      regulation of gene expression. Dysregulated expression of miRNAs in liver cancer
      is well documented, and the involvement of miRNAs in liver cancer initiation and
      progression has also been described. Cancer stem cells (CSCs) are a subset of
      cells known to be at the root of cancer recurrence and resistance to therapy. In
      this review, we highlight recent reports indicating that miRNAs participate in
      the regulation of liver cancer stem cells (LCSCs). The Wnt signaling pathway, TGF
      beta signaling pathway, JAK/STAT signaling pathway and epithelial-mesenchymal
      transition (EMT) are all closely correlated with the miRNA modulation of LCSCs.
      In addition, several miRNAs have been demonstrated to be involved in the
      regulation of LCSCs in response to therapy sensitivity. Targeting LCSCs by
      regulating the expression of these miRNAs represents a potential therapeutic
      strategy for treating cancer drug resistance, metastasis and recurrence in the
      near future.

PMID- 30094091
TI  - When human cells meet bacteria: precision medicine for cancers using the
      microbiota.
AB  - The human microbiota interacts with the host immune system in multiple ways to
      influence the development of diseases, including cancers; however, a detailed
      understanding of their relationship is unavailable. Accumulating evidence has
      only revealed an association rather than a causal link between microbial
      alterations and carcinogenesis. The regulatory loops among the microbiome, human
      cells and the immune system are far more complicated and require further studies
      to be revealed. In this review, we discuss the impact of the microbiota on cancer
      initiation, development and progression in different types of human cells, mainly
      focusing on the clinical translation from microbiome research to an accurate
      diagnosis, subtype classification and precision medicine.

PMID- 30094094
TI  - DLC2 inhibits development of glioma through regulating the expression ratio of
      TAp73alpha/TAp73beta.
AB  - To date, the anti-tumor mechanism of the deleted in liver cancer 2 (DLC2) in
      gliomas is still unclear. The study shows that TAp73alpha expression and
      TAp73alpha/TAp73beta ratio are frequently high in gliomas and that TAp73alpha and
      TAp73beta have opposite roles in regulating proliferation and apoptosis of glioma
      cells. Moreover, DLC2 is low-expressed in gliomas, which negatively correlates
      with TAp73alpha expression and TAp73alpha/TAp73beta ratio. More importantly, DLC2
      inhibits development of glioma by decreasing expression of TAp73alpha, which
      changes the expression ratio of TAp73alpha/TAp73beta in glioma cells.
      Mechanically, DLC2 interacts directly with TAp73alpha and induces TAp73alpha
      ubiquitination and degradation, which is mediated through SAM domain of DLC2 and
      TAp73alpha. In detail, DLC2 with SAM domain deletion fails to interact with
      TAp73alpha and induce TAp73alpha ubiquitination and degradation, and SAM deletion
      decreased tumorigenesis-inhibition effect of DLC2. In conclusion, DLC2 inhibits
      glioma development by inducing TAp73alpha degradation and subsequent change of
      TAp73alpha/TAp73beta expression ratio.

PMID- 30094095
TI  - Aryl hydrocarbon receptor activated by benzo (a) pyrene promotes SMARCA6
      expression in NSCLC.
AB  - Recent studies suggest that individual subunits of chromatin-remodeling complexes
      generate epigenetically specific signaling in tumorigenicity. The impact of
      environmental factors on the chromatin-remodeling factor has not been thoroughly
      elucidated to date. We detected the expression level of SMARCA6 (SWI/SNF2
      Related, Matrix-Associated, Actin-Dependent Regulator of Chromatin, Subfamily A,
      Member 6) in NSCLC (Non-small-cell lung carcinoma) and measured it through
      quantitative real-time PCR (qRT-PCR) and immunohistochemistry. The effects of BaP
      on proliferation and cell cycle progression were evaluated using MTT, colony
      formation and FACS analyses. Tumor growth in vivo was observed in a xenograft
      model. ChIP and qPCR were performed to validate that SMARCA6 was a potential
      target of AhR in NSCLC. As a result, BaP increased SMARCA6 expression. Smoking
      was linked with elevated SMARCA6 expression in NSCLC. BaP promoted cancer
      progression in vitro and in vivo. ChIP assay confirmed that BaP increases SMARCA6
      expression via recruitment of AhR and induces SMARCA6 expression by facilitating
      AhR translocation to the nucleus. Furthermore, inhibition of AhR expression
      decreases SMARCA6 expression in NSCLC. Finally, knockdown of SMARCA6 attenuates
      BaP-induced cancer progression. This study demonstrates that BaP promotes
      proliferation by activation of AhR, which promotes SMARCA6 expression, and may
      identify new diagnostic and therapeutic targets in lung cancer.

PMID- 30094096
TI  - MicroRNA-1292-5p inhibits cell growth, migration and invasion of gastric
      carcinoma by targeting DEK.
AB  - Gastric cancer ranks as the third most lethal cancer worldwide. Although many
      efforts have been made to identify novel markers for early diagnosis and
      effective drugs for the treatment of gastric cancer, the outcome is still poor
      due to delayed diagnosis and lack of therapeutic options. MicroRNAs (miRNAs) play
      crucial roles during tumorigenesis, and several miRNAs were found to be critical
      for gastric cancer development, offering promise as therapeutic targets. The
      results of this study indicate that a novel miRNA, miR-1292-5p, is downregulated
      both in gastric carcinoma in vivo and in gastric cancer cell lines in vitro. In
      addition, we showed that attenuation of miR-1292-5p inhibited the growth,
      migration and invasion of the AGS and SGC-7901 gastric cancer cell lines.
      Importantly, our results demonstrate that the proto-oncogenic protein DEK is a
      direct target of miR-1292-5p in gastric carcinoma. Our results therefore
      demonstrate a tumor suppressor role of miR-1292-5p in gastric carcinoma and hint
      at the diagnostic and therapeutic potential of the miR-1292-5p/DEK pathway in
      gastric cancer.

PMID- 30094097
TI  - Trametinib suppresses chemotherapy-induced cold and mechanical allodynia via
      inhibition of extracellular-regulated protein kinase 1/2 activation.
AB  - Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of
      some anti-cancer drugs and leads to discontinuation of chemotherapy and
      detrimental dose reductions, thereby affecting the quality of life of cancer
      patients. Currently, no treatment can effectively prevent or treat chemotherapy
      induced neuropathy. Therefore, understanding its underlying molecular mechanisms
      may help to identify novel therapies for treating it. Some disease-induced
      neuropathy involve the activation of mitogen-activated protein kinases (MAPKs),
      such as extracellular-regulated protein kinase 1/2 (ERK1/2). In the present
      study, we investigated whether ERK1/2 inhibition can prevent chemotherapy-induced
      neuropathy. We found that trametinib, an MEK inhibitor, suppressed oxaliplatin-,
      paclitaxel-, vincristine-, and bortezomib-induced cold and mechanical allodynia
      in mice. In addition, treatment with oxaliplatin, paclitaxel, vincristine, or
      bortezomib enhanced ERK1/2 and c-Jun N-terminal kinase (JNK) phosphorylation in
      the spinal cord lumbar segments 4-6, and when combined with trametinib, can
      prevent chemotherapy-induced neuropathy via the suppression of ERK1/2 activation,
      but does not affect JNK activation. In conclusion, we demonstrated that the
      disruption of this pathway by MEK inhibitors suppresses oxaliplatin-, paclitaxel
      , vincristine-, and bortezomib-induced neuropathy. This suggests that inhibition
      of the MEK/ERK pathway could prevent chemotherapy-induced neuropathy and MEK
      inhibitors could be used in combination with anti-tumor drugs during
      pharmacotherapy.

PMID- 30094098
TI  - Downregulation of CEACAM6 gene expression in laryngeal squamous cell carcinoma is
      an effect of DNA hypermethylation and correlates with disease progression.
AB  - We have turned our attention to CEACAM6 gene, already described as deregulated in
      various types of cancer. By using the expression microarrays performed on the set
      of 16 laryngeal squamous cell carcinoma (LSCC) samples: 11 cell lines and 5
      primary tumors we have shown downregulation of CEACAM6 gene as compared to non
      cancer controls from head and neck region. CEACAM6 gene downregulation, further
      confirmed by quantitative PCR on 25 LSCC cell lines, was observed in cell lines
      derived from recurrent tumors in comparison to controls. A significant gene
      downregulation was observed in cell lines derived from advanced, high grade
      tumors in comparison to controls. Intrigued by the recurrent transcriptional loss
      of CEACAM6 we searched for the mechanism potentially responsible for its
      downregulation and hence we analyzed DNA copy number changes (a-CGH), promoter
      DNA methylation status and occurrence of gene mutations (in silico). Neither the
      analysis of gene copy number, nor the mutation screen has shown recurrent
      deletions or mutations, that could contribute to the observed downregulation of
      the gene. However, by using bisulfite pyrosequencing, we have shown DNA
      hypermethylation (mean DNA methylation > 78%) of CEACAM6 promoter region in 9/25
      (36%) LSCC cell lines. Importantly, the 5-aza-2-deoxycytidine-induced inhibition
      of DNA methylation resulted in restoration of CEACAM6 expression in the two LSCC
      cell lines on mRNA level. In summary, we have shown that recurrent downregulation
      of CEACAM6 in LSCC is dependent on the gene's promoter DNA methylation and is
      observed predominantly in large, poorly differentiated tumors and recurrences.

PMID- 30094099
TI  - Impact of first-line treatment on outcomes of Ewing sarcoma of the spine.
AB  - The optimal first-line treatment for primary Ewing sarcoma (ES) of the spine is
      unclear, especially when the patients present with acute neurological deficits.
      This study aimed to retrospectively analyze the effect of first-line treatment
      with surgery or chemotherapy on neurological and survival outcomes of ES of the
      spine. 39 patients treated between January 2005 and December 2016 were included
      in the present analysis. 29 (74.4%) presented with symptomatic spinal cord
      compression at diagnosis. 21 patients were submitted to primary surgery followed
      by chemotherapy and local radiotherapy, while 18 patients received induction
      chemotherapy before surgery and/or local radiotherapy. Neurological deficit
      before and after treatment, event-free survival and overall survival were
      analyzed. The results indicated that chemotherapy as the first-line treatment
      could achieve similar results as primary surgery in preserving neurological
      function, even in case of major neurological deficits. Compared with primary
      surgery, induction chemotherapy contributed to a higher rate of en bloc resection
      with a microscopic negative margin (R0) of primary tumor (72.7% vs. 28.6%, P <
      0.05). Multivariate Cox regression analyses revealed that initial chemotherapy
      was a favorable independent prognostic factor of event-free survival (hazard
      ratio, 0.215; 95% confidence interval, 0.077-0.596; P = 0.003) and overall
      survival (hazard ratio, 0.288, 95% confidence interval, 0.098-0.852; P = 0.024).
      In conclusion, our study suggests that first-line treatment of ES of the spine
      should be induction chemotherapy, even in case of major neurological deficits.

PMID- 30094100
TI  - Long non-coding RNA LINC00673 promotes breast cancer proliferation and metastasis
      through regulating B7-H6 and epithelial-mesenchymal transition.
AB  - BACKGROUND: Long non-coding RNAs (LncRNAs) have been reported as key regulators
      of tumor progression in recent decades. However, the potential molecular
      mechanisms of breast cancer are still unclear. With the development of sequencing
      technology, we discovered that LINC00673 is upregulated in tumor tissues. But the
      main role of LINC00673 in breast cancer has yet to be confirmed. MATERIALS AND
      METHODS: 35 pairs of breast tumors and normal tissues were selected to real-time
      quantitative polymerase chain reaction (RT-qPCR) to validate LINC00673 is
      overexpressed in tumor tissues. We conducted proliferation, colony formation,
      migration, invasion assays, and EMT-related phenotype to determine the specific
      role of LINC00673 in breast cancer cell lines (MDA-MB-231, BT-549, and MCF-7)
      transfected with small interfering RNA. Gene expression profiling was conducted
      to found LINC00673-associated gene transcriptional changes. RESULTS: We
      discovered that LINC00673 is significantly upregulated in breast cancer tissues
      compared to paired adjacent non-tumor tissues by RT-qPCR and highly expressed
      LINC00673 is positively correlated with lymph node metastasis and clinical stage
      in the validated cohort. Knocking down LINC00673 inhibited cell proliferation and
      metastasis, whereas upregulated LINC00673 had the opposite effect. Gene
      expression profiling results indicated that LINC00673 could influence NCR3LG1(B7
      H6) expression in transcriptional level. Western Blot showed us that LINC00673
      could regulate epithelial-mesenchymal transition (EMT) and B7-H6 in protein
      level. Then we demonstrated that knocking down B7-H6 could decrease breast cancer
      cell proliferation and metastasis. CONCLUSION: In this study, we identified the
      role of LINC00673 in inducing proliferation and metastasis of breast cancer cell
      lines and it might act as an underlying therapeutic target for breast cancer.

PMID- 30094101
TI  - Bufalin inhibits glycolysis-induced cell growth and proliferation through the
      suppression of Integrin beta2/FAK signaling pathway in ovarian cancer.
AB  - Bufalin is the major digoxin-like component of the traditional Chinese medicine
      Chansu and has obvious anti-tumor effect in major malignancies, but the role of
      bufalin in glucose metabolism in ovarian cancer remains illustrated. Here, we
      sought to elucidate the regulatory function of bufalin on cell glucose metabolism
      in ovarian cancer. The treatment of bufalin on ovarian cancer cells effectively
      inhibited glucose uptake and lactate production in ovarian cancer cells. The
      expression levels of glycolysis-related proteins, including GLUT4, LDHB and HK2,
      were decreased by the treatment of bufalin detected by qRT-PCR and
      immunoblotting. Mechanistically, bufalin exerted its anti-tumor effect by
      targeting ITGB2/FAK signaling pathway in vitro and in vivo, which could be
      rescued by the introduction of ITGB2 cDNA in ovarian cancer cells. These findings
      provide evidence that bufalin inhibited cellular glycolysis-induced cell growth
      and proliferation through repression of the ITGB2/FAK pathway, indicating that
      bufalin may be developed as a chemotherapeutic agent to treat ovarian cancer.

PMID- 30094103
TI  - Inhibition of ATR downregulates PD-L1 and sensitizes tumor cells to T cell
      mediated killing.
AB  - The ataxia telangiectasia and Rad3-related (ATR) kinase plays a crucial role in
      maintaining genome stability in response to DNA damage. Once activated, ATR acts
      via its downstream target to arrest the cell cycle, promote DNA repair, and
      enhance cell survival. Therefore, ATR has become an attractive therapeutic target
      in cancer therapy. Multiple clinical studies have demonstrated that ATR
      inhibitors can sensitize cancer cells to conventional DNA damaging agents.
      However, the potential effects of ATR inhibitors on immune response in the tumor
      microenvironment, especially on the expression of immune checkpoint-related
      proteins, remain elusive. Here we show that DNA damaging agents, such as ionizing
      radiation and cisplatin, significantly induce cell surface PD-L1 expression in
      various cancer cell types. This effect is blocked by depletion or pharmacological
      inhibition of ATR, suggesting the essential role of ATR in DNA damage-induced PD
      L1 expression. Mechanistically, we show that disruption of ATR destabilizes PD-L1
      in a proteasome-dependent manner. Furthermore, clinical ATR kinase inhibitor
      downregulates PD-L1 expression to attenuate PD-L1/PD-1 interaction and sensitize
      cancer cells to T cell killing. Collectively, our findings indicate that in
      addition to potentiating DNA damage, ATR inhibitor concurrently downregulates PD
      L1 levels and enhances anti-tumor immune responses. Moreover, our data reveal a
      potential crosstalk between DNA damage response signaling and immune checkpoints,
      providing a rationale for the combination therapy of ATR inhibitor and immune
      checkpoint blockade.

PMID- 30094102
TI  - Cabazitaxel, a novel chemotherapeutic alternative for drug-resistant
      hepatocellular carcinoma.
AB  - The prognosis of advanced hepatocellular carcinoma (HCC) patients remains
      extremely poor, partially due to the development of acquired resistance to
      sorafenib and chemotherapy. Cabazitaxel, a semisynthetic taxane, has been
      approved for the therapy of docetaxel-resistant prostate cancer. However, no
      studies have been performed on the effect of cabazitaxel on HCC, and whether
      cabazitaxel remains sensitive in chemotherapy-resistant and sorafenib-resistant
      HCC cells is not clear. Our results demonstrate that cabazitaxel is highly toxic
      to HCC cell lines in a time- and dose-dependent manner by inducing G2/M phase
      arrest and apoptosis in vitro. Cabazitaxel also significantly suppresses HCC
      tumor growth in vivo. In chemotherapy-resistant HCC cell Huh-TS-48 with P-gp
      overexpression, cabazitaxel shows less cross-resistant to other chemotherapeutic
      agents. The resistance fold of cabazitaxel, doxorubicin, paclitaxel, docetaxel
      and vinorelbine is 1.53, 8.60, 38.58, 15.53 and 18.06 respectively. Furthermore,
      sorafenib-resistant HCC cell SK-sora-5 is still sensitive to cabazitaxel. The
      IC50 values of cabazitaxel after 72 h exposure for parental cell SK-hep-1 and
      resistant cell SK-sora-5 are 0.84 and 0.73 nM. The results indicate that
      cabazitaxel is a potential agent to treat HCC after developing chemotherapy
      resistance caused by overexpression of P-gp and acquired resistance to sorafenib,
      and might improve prognosis in advanced HCC patients.

PMID- 30094105
TI  - Lessons Learnt from Epidemiological Investigation of Lassa Fever Outbreak in a
      Southwest State of Nigeria December 2015 to April 2016.
AB  - INTRODUCTION: An outbreak of Lassa Fever (LF) reported and confirmed in Ondo
      state, Southwest Nigeria in January 2016 was investigated. This paper provides
      the epidemiology of the LF and lessons learnt from the investigation of the
      outbreak. METHODS: The incidence management system (IMS) model was used for the
      outbreak coordination. Cases and deaths were identified through the routine
      surveillance system using standard definitions for suspected and confirmed cases
      and deaths respectively. Blood specimens collected from suspect cases were sent
      for confirmation at a WHO accredited laboratory. Active case search was
      intensified, and identified contacts of confirmed cases were followed up for the
      maximum incubation period of the disease. Other public health responses included
      infection prevention and control, communication and advocacy as well as case
      management. Data collected were analysed using SPSS 20, by time, place and
      persons and important lessons drawn were discussed.   Results: We identified 90
      suspected LF cases of which 19 were confirmed by the laboratory. More than half
      (52.6%) of the confirmed cases were females with majority (73.7%) in the age
      group >= 15 years. The Case Fatality Rate (CFR) of 63.2% among the laboratory
      confirmed positive cases where 9 of 19 cases died, was significantly higher
      compared to the laboratory confirmed negative cases where 6 of the 65 cases died
      ( CFR; 8.5%) p <= 0.05. Two hundred and eighty-seven contacts of the confirmed
      cases were identified, out of which 267(93.0%) completed  the follow-up without
      developing any symptoms and 2 (0.7%) developed symptoms consistent with LF and
      were confirmed by the laboratory. More than half of the contacts were females
      (64.5%) with most of them (89.2%) in the age group >= 25 years.   Discussion: One
      key lesson learnt from the investigation was that the confirmed cases were mainly
      primary cases; hence the needs to focus on measures of breaking the chain of
      transmission in the animal-man interphase during Lassa fever epidemic
      preparedness and response. In addition, the high case fatality rate despite early
      reporting and investigation suggested the need for a review of the case
      management policy and structure in the State. Key Words: Lassa fever, Outbreak
      Response, Incident Management System, Nigeria.

PMID- 30094107
TI  - Mycobacterium Chimaera: A Rare Presentation.
AB  - Mycobacterium chimaera is an indolent nontuberculous mycobacterium which is
      abundant in soil, dust, and water. Although lacking recognition garnered by other
      mycobacteria (i.e., M. tuberculosis), it has been recognized as an emerging
      opportunistic threat to patients undergoing coronary bypass surgery and open
      heart procedures requiring extracorporeal devices. Here, we present a case of an
      individual initially seen in the inpatient setting without a history of such
      procedures or other risk factors commonly associated with mycobacterium-laden
      infections.

PMID- 30094106
TI  - Surgical planning for living donor liver transplant using 4D flow MRI,
      computational fluid dynamics and in vitro experiments.
AB  - This study used magnetic resonance imaging (MRI), computational fluid dynamics
      (CFD) modeling, and in vitro experiments to predict patient-specific alterations
      in hepatic hemodynamics in response to partial hepatectomy in living liver
      donors. 4D Flow MRI was performed on three donors before and after hepatectomy
      and models of the portal venous system were created. Virtual surgery was
      performed to simulate (1) surgical resection and (2) post-surgery vessel
      dilation. CFD simulations were conducted using in vivo flow data for boundary
      conditions. CFD results showed good agreement with in vivo data, and in vitro
      experimental values agreed well with imaging and simulation results. The post
      surgery models predicted an increase in all measured hemodynamic parameters, and
      the dilated virtual surgery model predicted post-surgery conditions better than
      the model that only simulated resection. The methods used in this study have
      potential significant value for the surgical planning process for the liver and
      other vascular territories.

PMID- 30094104
TI  - Chemoresistance and targeting of growth factors/cytokines signalling pathways:
      towards the development of effective therapeutic strategy for endometrial cancer.
AB  - Endometrial cancer tends to be an aggressive malignancy. Although the disease
      prognosis can be good at the early stages of disease, the advanced condition is
      not curable. Chemotherapy regimens and hormone-based therapy in combination with
      surgery are major approaches for the management of endometrial cancers. However,
      intrinsic chemoresistance reduces the success rate and increases the possibility
      of disease relapse. Investigation of underlying mechanisms revealed altered
      activation of PI3K/AKT, MAPK, fibroblast growth factor (FGF), mTOR and WNT
      pathways and reduced gene expression of tumor suppressor p53 in recurrent
      endometrial cancer. A PTEN mutation, deletion or degradation induces positive p
      AKT expression, while PI3K knock-down increases the level of pro-apoptotic
      proteins and decreases the level of anti-apoptotic ones in cancerous cells.
      Additionally, RAS proteins trigger both the RAF-MEK-ERK and PI3K-PTEN-AKT
      signalling mechanisms, thus conferring resistance to anti-tumor agents. FGF up
      regulates angiogenesis via receptor-mediated tyrosine kinase activation. Single
      nucleotide polymorphism, gene amplification or missense mutations of FGFR2 are
      associated with endometrial cancer. The mTOR complex integrates the nutrient and
      mitogen signals via AMPKs, S6 kinase 1 (S6K1) and eukaryotic initiation factors,
      causing unrestricted endometrial cellular proliferation. WNT signalling
      molecules, such as frizzled receptors, beta-catenin, PORCN, RSPO3 and DKK1
      undergo dysregulation, and drugs targeting these pathways are under clinical
      trials in patients with endometrial cancer. Common therapies for endometrial
      tumor include platinum-based anti-neoplastics, taxanes, nucleoside analogues,
      immune modulators, FGFR and tyrosine kinase inhibitors, small-molecule mTOR
      inhibitors and drugs that trigger cell cycle arrest in the G1 phase. Taken
      together, the current review elucidates the mechanism underlying endometrial
      cancer, existing therapies and chemoresistance, and points towards the need for
      novel therapeutics that may promote disease-free survival.

PMID- 30094108
TI  - Recurrent Mesenteric Ischemia from Celiomesenteric Trunk Stenosis.
AB  - A common origin of the celiac trunk and superior mesenteric artery (SMA), also
      termed as celiomesenteric trunk (CMT), is a rare occurrence. We report a rare
      case of symptomatic CMT stenosis requiring multiple interventions. The patient
      underwent an initial superior mesenteric artery bypass graft but required a
      subsequent endoluminal intervention. We present this case for the rarity of CMT
      stenosis and its potential to cause recurrent mesenteric ischemia. The treatment
      outcome in this patient suggests that revascularization of the SMA alone can
      result in adequate perfusion of the entire mesenteric bed and resolve symptoms of
      mesenteric ischemia including weight loss and food avoidance.

PMID- 30094110
TI  - Primary Herpes Simplex Virus Infection Mimicking a Cervical Malignancy in an
      Immunocompetent Individual.
AB  - Herpes simplex virus (HSV) is a common sexually transmitted infection. Although
      primary HSV typically presents with ulcerations, atypical presentations are
      possible. Only one other case report of HSV manifesting as a cervical mass
      exists. A 35-year-old immunocompetent female with dysuria was found to have a
      cervical mass concerning for cancer. She had a history of abnormal pap smears and
      a loop electrosurgical excision procedure (LEEP) with poor follow-up. The patient
      was taken to the operating room for biopsies and staging and was found to have
      new vulvar ulcers. The biopsies confirmed an HSV infection with cervical,
      bladder, and vulvar involvement and were negative for cervical neoplasia. This
      report examines an atypical presentation of a primary HSV infection and reviews
      the literature regarding the association of HSV with cervical cancer.

PMID- 30094109
TI  - A Case of Brugada Pattern Associated with Adrenal Insufficiency.
AB  - Brugada syndrome (BrS) is an inherited channelopathy disease, caused by genetic
      changes in transmembrane ion channels. It has an increased risk of sudden cardiac
      death (SCD) in the absence of a structural heart disease. We report a case in
      which the presenting electrocardiogram (EKG) exhibited a type 1 Brugada-like
      pattern during an adrenal crisis with transformation into a type 2 Brugada-like
      pattern as the crisis improved.

PMID- 30094111
TI  - Diagnosing Necrotizing Fasciitis Using Procalcitonin and a Laboratory Risk
      Indicator: Brief Overview.
AB  - Necrotizing fasciitis is a progressive inflammatory disease that requires an
      early diagnosis to avoid limb salvage and other deadly manifestations. The
      current protocol is the microbiological and histopathological sampling of the
      tissue. Once the diagnosis is made, it should be managed with antimicrobial
      therapy, debridement, and surgical interventions. Such interventions can be
      invasive and increase the time to treat, which may increase morbidity. Our
      article discusses procalcitonin, C-reactive protein, and other markers, such as
      "pain out of proportion," lactate, creatinine, and creatine kinase, to make a
      quicker diagnosis before proceeding with invasive procedures. We discussed a
      similar non-invasive approach called the "Laboratory Risk Indicator for
      Necrotizing Fasciitis" scoring system that can aid in the early diagnosis of
      necrotizing fasciitis, which can prompt rapid empiric therapy, reducing the
      chances of morbidity. This scoring system comprises C-reactive protein, white
      blood cell count, hemoglobin level, creatinine, sodium, and glucose. Such non
      invasive, bedside, and quick tests can help in reducing the time required to make
      the diagnosis and can affect the course of the disease, hence, improving patient
      outcomes.

PMID- 30094112
TI  - A Summary of the Anatomy and Current Regional Anesthesia Practices for
      Postoperative Pain Management in Total Knee Arthroplasty.
AB  - The planning and implementation of an effective postoperative pain management
      program depend on the surgical technique for total knee arthroplasty (TKA), the
      type of regional anesthesia, and the multimodal analgesia regimen. It is
      imperative to understand the surgical anatomy of TKA and the relevant nerve
      supply of the knee for optimum perioperative patient satisfaction with respect to
      pain management in the patient undergoing TKA. The commonly used regional
      techniques have their own specific benefits and limitations. The ideal
      postoperative pain management should be customized for a patient to achieve the
      goals of effective pain control, early ambulation, faster recovery, and
      discharge.

PMID- 30094113
TI  - Sugar Beverages and Dietary Sodas Impact on Brain Health: A Mini Literature
      Review.
AB  - Sugar-sweetened beverages containing caffeine are widely used among humans
      nowadays and can have negative consequences on the overall health. Our study aims
      to discuss the effects of these sugar-sweetened beverages (SSB) and how they can
      impact the health in different ways particularly on the brain. Some of the
      mechanisms by which soft drinks can exert adverse effects include an increase in
      glutathione-6-dehydrogenase level, increased levels of gamma-aminobutyric acid
      (GABA), glutamate and dopamine alteration in brain waves on
      electroencephalography (EEG) eventually leading to stroke and dementia. They can
      increase the oxidative stress by a decreasing monoamine oxidase and acetylcholine
      esterase and antioxidants such as glutathione and catalase. The sleep quality and
      duration of sleep is also significantly affected by their increased consumption.
      Also, the consumption of sodium benzoate (found in beverages) on impairing
      memory, motor coordination, affecting reduced glutathione (GSH), increasing the
      malondialdehyde (MDA) level in the brain and producing attention deficit
      hyperactivity disorder (ADHD) in children is emphasized. Finally, we will
      highlight how diet drinks can also be harmful and the maternal consumption of
      chocolate or soft drinks during pregnancy and postnatal period can be linked to
      cognitive impairment and child obesity.

PMID- 30094114
TI  - Gastrointestinal Bleed from Erosive Gastritis and Duodenitis: A Sentinel Event of
      Invasive Lobular Carcinoma of the Breast and a Diagnostic Dilemma.
AB  - Metastasis from breast cancer to the gastrointestinal (GI) tract is uncommon, and
      such events presenting as GI bleeding are exceedingly rare. In some individuals,
      the absence of classical findings of primary breast cancer coupled with the non
      specific nature of GI symptoms may make early detection and diagnosis
      challenging. Our patient is a 75-year-old female who presented with symptomatic
      anemia manifesting as progressive dizziness, weakness, and early satiety that
      developed eight days after right knee arthroplasty. She had a remote history of
      acid reflux disease and reported regular use of non-steroidal anti-inflammatory
      drugs (NSAIDs). Physical examination was notable for pallor and tachycardia; the
      cardiopulmonary examination was otherwise unremarkable and the abdominal
      examination was normal. A fecal occult blood test was positive. Subsequent
      esophagogastroduodenoscopy demonstrated significant erosive gastritis and
      duodenitis that was initially attributed to the patient's NSAID use. However,
      biopsy showed signet ring carcinoma. No gastric primary tumor was identified on
      work up. Extensive evaluation ultimately revealed invasive lobular carcinoma of
      the breast. Notably, no primary breast lesion had been detected on physical
      examination or breast mammography or magnetic resonance imaging (MRI). Therapy
      for invasive lobular carcinoma of the breast is substantially different from
      gastric carcinoma and thus it is important to accurately diagnose the condition
      early in its course to optimize patient outcomes.

PMID- 30094115
TI  - A Rare Case of Severe Idiopathic Stuttering Priapism in a Young Healthy Man.
AB  - Priapism, a persistent erection of the penis which has no association with sexual
      activity and lasts longer than four hours, is a urologic emergency. It can be
      classified into ischemic, nonischemic, and stuttering categories. The
      pathophysiology of stuttering priapism is not well understood; however, the
      dysregulation of nitric oxide and phosophodiesterase-5 (PDE5) has been put
      forward as a possible mechanism. A 35-year-old male with a history of recurrent
      priapism presented with continuous penile erection for more than 48 hours. In the
      emergency room, penile aspiration and an intracavernous phenylephrine injection
      were attempted which did not help. Subsequently, a distal penile shunt was
      surgically created; however, the patient's symptoms still persisted. A second
      round of penile irrigation, aspiration, and an intracavernous phenylephrine
      injection were attempted, but it was not helpful. Finally, another surgical shunt
      was created bilaterally between the corpora cavernosa and corpus spongiosum,
      which led to complete resolution of symptoms in the next 24 hours. The patient
      received an injection of lupron, and he was discharged.

PMID- 30094116
TI  - Inter-surgeon Variability in Cystic Artery Lymph Node Excision during
      Laparoscopic Cholecystectomy.
AB  - Introduction Expert opinion recommends that surgeons perform a laparoscopic
      cholecystectomy (LC) in a standardized manner by dissecting the hepatobiliary
      triangle lateral to the cystic artery lymph node (LN) to minimize the rate of a
      major bile duct injury. Methods To determine whether surgeons performed a
      laparoscopic cholecystectomy in a standardized manner, the study assessed the
      variability in the frequency of an LN excision. All LCs that were performed at a
      single hospital were identified from a prospective dataset. The presence of an LN
      was retrospectively determined from the histology report. Results Twenty-seven
      surgeons were recorded to have performed 2332 laparoscopic cholecystectomies. Out
      of the total number of patients, 76.8% were female. The median patient age was
      42.4 years. About 60.8% of the LCs were elective, while 39.2% of them were acute.
      Nineteen pathologists reported that in 99% of the specimens - the LN status of
      1831 (78.5%) gallbladders was reported and analyzed. Overall, the LN yield per
      surgeon varied from 0% to 50% (mean 18.7%). Conclusion  The high inter-surgeon
      variability in the rate of LN excision during laparoscopic cholecystectomy shows
      that surgeons dissect the hepatobiliary triangle differently. The LN yield may
      also represent a surrogate marker of surgical technique (which is easy to
      measure).

PMID- 30094117
TI  - Syncopal Episodes of Arrhythmogenic Right Ventricular Cardiomyopathy in a Patient
      with Pre-existing Seizure Disorder.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC), is a heritable condition
      that is an important, and under-recognized cause of sudden cardiac death.
      Microscopically, it is represented by fibrofatty replacement of myocardium
      involving the right ventricular inflow area, apex, and infundibulum. Common
      clinical manifestations of ARVC include palpitations, syncope, chest pain,
      dyspnea, and sudden cardiac death. This is a case of a 25-year-old male with a
      history of thalassemia, and tonic-clonic seizure status post head trauma with
      cystic encephalomalacia in left parietal lobe who described recurrent syncope. He
      was followed by neurology and maintained only on Lamotrigine. Episodes occurred
      within the span of four weeks and were without prodrome, lasting only a few
      seconds. On evaluation, blood pressure was 123/69 mmHg. Neurologic exam was
      grossly normal. Heart was regular rate and rhythm without gallops, murmur, or
      rub. An EKG showed normal sinus rhythm with an incomplete right bundle branch
      block and Epsilon waves in leads V1 and V2 without evidence of Brugada syndrome.
      The patient was admitted and had a 24-hour electroencephalogram that showed no
      seizure activity. A 2D Echo showed normal left ventricular function and no
      valvular disease. Eventual cardiac magnetic resonance imaging (MRI) showed small
      focal outpouchings of the right ventricular free wall. A diagnosis of ARVC was
      achieved, and the patient underwent electrophysiology (EP) study and successful
      implantation of a dual-chamber cardioverter defibrillator.

PMID- 30094118
TI  - Same-day Smear Method Compared with Conventional Sputum Method for Diagnosing
      Pulmonary Tuberculosis.
AB  - Background Patient compliance with the two-day Revised National Tuberculosis
      Control Programme's (RNTCP) diagnostic process for pulmonary tuberculosis (TB) is
      poor in high case load settings, with a high dropout rate observed on the second
      day. Hence, the World Health Organization (WHO) has recommended the same-day
      (spot-spot) sputum test for high-burden TB countries to help reduce diagnostic
      dropouts. This study addresses the paucity of comparative data on the accuracy
      and agreement of the two methods, while the WHO recommendations are yet to be
      implemented by the RNTCP. The objective of this study was to assess and compare
      the smear positivity rates of the same-day and conventional sputum examination
      methods for the diagnosis of sputum smear-positive pulmonary TB. Methodology We
      conducted a cross-sectional, analytical, nonrandomized comparative study on
      presumptive TB patients attending a designated microscopy center in a tertiary
      care hospital. Three sputum samples were collected: a first spot, a second spot
      (one hour after the first spot), and an early morning sample taken on the
      following day. The first and the second spot samples taken one hour apart were
      included for microscopic analysis. The conventional (i.e., two-day sputum) method
      used the first spot and the early morning sputum sample taken on the following
      day. A positive result from any one of the three sputum samples was recorded as a
      proven TB case. We then compared the results of the smear microscopy obtained by
      the two methods. Results The same-day sputum microscopic method diagnosed 181 out
      of a total 189 TB cases. The conventional method diagnosed 188 cases. Thus, same
      day sputum microscopy missed eight cases, whereas the conventional method missed
      only one case. The sputum positivity rate was 18.8% in the same-day sputum
      microscopy samples and 19.5% in the conventional method samples. The incremental
      yield of the second sputum sample in the same-day (second spot) sample was five
      cases (2.7%). In the conventional method (early morning sample), the yield was 12
      cases (6.3%). The sensitivity of the same-day microscopy and conventional methods
      were 95.76% and 99.5%, respectively. Conclusion The conventional method of
      diagnosing sputum-positive pulmonary TB had more sensitivity compared to the same
      day sputum microscopy approach.

PMID- 30094119
TI  - Challenges in Hip Replacement in Hip Dysplasia Cases and the "Happy Elephant
      Sign.
AB  - Hip dysplasia is an abnormal development of the hip that consists of a spectrum
      of different abnormalities featuring an abnormal relation of the femoral head to
      the acetabulum. It can be treated in early childhood when it is diagnosed. Later
      in adult life, it is more challenging. We present a case of a 50-year-old woman
      who presented to us with adult hip dysplastic changes; we undertook the care of
      her left hip and treated her surgically.

PMID- 30094120
TI  - Stimulation of murine cell-mediated immunity by dietary administration of a cell
      preparation of Enterococcus faecalis strain KH-2 and its possible activity
      against tumour development in mice.
AB  - It is well known that dietary lactic acid bacteria (LAB) stimulate cell-mediated
      immunity such as natural killer (NK) activity in mice. Here, we aimed to assay
      the immunomodulatory effects of a cell preparation of Enterococcus faecalis
      strain KH-2 (CPEF). We further evaluated the possibility of antitumour activity
      caused by CPEF administration, because NK cells actively participate in the
      prevention of tumour formation. NK cell activity and gene expression of IFN-gamma
      and Perforin 1, which were induced most likely by a synergetic action of their
      cytotoxic activity, were higher in splenocytes of CPEF-administered mice than
      they were in control mice. Moreover, unlike those of control mice, the
      splenocytes of CPEF-administered mice had significantly higher CD28+CD69+/CD4+
      and CD28+CD69+/CD8+ ratios that resulted in a survival rate with a tendency
      toward improvement after 47 days of CPEF administration (p=0.1) in Meth-A
      fibrosarcoma-bearing mice. In conclusion, we showed that CPEF might be effective
      in treating Meth-A fibrosarcoma in mice, as it helped increase their survival
      rate via stimulation of an immune response in splenocytes, which involved
      systemic cellular immunity processes such as cytotoxic activity, and active T
      cells.

PMID- 30094121
TI  - Effects of heat-killed Lactobacillus casei subsp. casei 327 intake on defecation
      in healthy volunteers: a randomized, double-blind, placebo-controlled, parallel
      group study.
AB  - Lactobacillus casei subsp. casei 327 (L. casei 327) was isolated from brown rice.
      A preliminary study showed that intake of 50 mg of heat-killed L. casei 327 is
      effective in improving defecation. In this study, we conducted a randomized,
      double-blind, placebo-controlled, parallel-group trial to investigate the effect
      of intake of heat-killed L. casei 327 (25 mg: approximately 5 * 1010 bacteria) on
      defecation in healthy volunteers with relatively low defecation frequencies. We
      selected 104 healthy Japanese adults with relatively low defecation frequencies
      (approximately 3-5 times a week) by screening and pretrial tests. Subjects (n=52
      in each group) were randomly given a tablet containing L. casei 327 (group A) or
      a placebo tablet (group P) daily for 2 weeks. After eliminating data for 9
      subjects who met the exclusion criteria for efficacy analysis, data for 95
      subjects were analyzed. The defecation frequency and number of defecation days
      during the intake period and their changes from the pretrial period were
      significantly higher in group A than in group P. The fecal volume during the
      intake period was higher in group A than group P, but the difference was not
      statistically significant. However, the change from the pretrial period was
      significantly higher in group A than in group P. There were no significant
      differences between groups in the values of fecal shape, color, odor, and feeling
      after defecation. These results suggested that intake of L. casei 327 improves
      defecation in healthy adults who have relatively low defecation frequencies.

PMID- 30094123
TI  - Intrinsic Dynamic Nature of Neutral Hydrogen Bonds Elucidated with QTAIM Dual
      Functional Analysis: Role of the Compliance Force Constants and QTAIM-DFA
      Parameters in Stability.
AB  - Invited for this month's cover picture is Professor Satoko Hayashi's group from
      the Faculty of Systems Engineering at Wakayama University (Japan). The cover
      picture shows Japanese lanterns for the Bon festival dance dangling on two ropes,
      and several molecular graphs with contour maps for hydrogen bonds (HBs) emerging
      from the lanterns. The curves of the ropes may correspond to the DeltaE (energy
      of formation) and Cij (compliance constant) values for HBs, for which the product
      will be constant. Read the full text of their Full Paper at
      https://doi.org/10.1002/open.201800051.

PMID- 30094122
TI  - Effects of Bifidobacterium breve B-3 on body fat reductions in pre-obese adults:
      a randomized, double-blind, placebo-controlled trial.
AB  - Accumulating evidence suggests a relationship between the gut microbiota and the
      development of obesity, indicating the potential of probiotics as a therapeutic
      approach. Bifidobacterium breve B-3 has been shown to exert anti-obesity effects
      in high-fat diet-induced obese mice. In the present study, the anti-obesity
      effects of the consumption of B. breve B-3 by healthy pre-obese (25 <= BMI < 30)
      adults were investigated in a randomized, double-blind, placebo-controlled trial
      (trial registration: UMIN-CTR No. 000023919; preregistered on September 2, 2016).
      Eighty participants were randomized to receive placebo or B. breve B-3 capsules
      (2 * 1010 CFU/day) daily for 12 weeks. The visceral fat area significantly
      increased at weeks 4 and 8 in the placebo group only; no significant change was
      observed in the B-3 group. Body fat mass and percent body fat were significantly
      lower in the B-3 group than in the placebo group at weeks 8 and 12 (p<0.05,
      ANCOVA adjusted with baseline values). Although no significant differences were
      observed in blood parameters between the groups, the intake of B. breve B-3
      slightly decreased triglyceride levels and improved HDL cholesterol from the
      baseline. No serious adverse effects were noted in either group. These results
      suggest that the probiotic strain B. breve B-3 has potential as a functional food
      ingredient to reduce body fat in healthy pre-obese individuals.

PMID- 30094124
TI  - Intrinsic Dynamic Nature of Neutral Hydrogen Bonds Elucidated with QTAIM Dual
      Functional Analysis: Role of the Compliance Force Constants and QTAIM-DFA
      Parameters in Stability.
AB  - The dynamic and static nature of various neutral hydrogen bonds (nHBs) is
      elucidated with quantum theory of atoms-in-molecules dual functional analysis
      (QTAIM-DFA). The perturbed structures generated by using the coordinates derived
      from the compliance force constants (Cij ) of internal vibrations are employed
      for QTAIM-DFA. The method is called CIV. The dynamic nature of CIV is described
      as the "intrinsic dynamic nature", as the coordinates are invariant to the choice
      of the coordinate system. nHBs are, for example, predicted to be van der Waals
      (H2Se-?-HSeH; ?=bond critical point), t-HBnc (typical-HBs with no covalency: HI-?
      HI), t-HBwc (t-HBs with covalency: H2C=O-?-HI), CT-MC [molecular complex
      formation through charge transfer (CT): H2C=O-?-HF], and CT-TBP (trigonal
      bipyramidal adduct formation through CT: H3N-?-HI) in nature. The results with
      CIV were the same as those with POM in the calculation errors, for which the
      perturbed structures were generated by partial optimization, and the interaction
      distances in question were fixed suitably in POM. The highly excellent
      applicability of CIV for QTAIM-DFA was demonstrated for the various nHBs, as well
      as for the standard interactions previously reported. The stability of the HBs,
      evaluated by DeltaE, is well correlated with Cij (DeltaE*Cij =constant value of 
      165.64), and the QTAIM parameters, although a few deviations were detected.

PMID- 30094125
TI  - Mechanochemical Synthesis of Iron and Cobalt Magnetic Metal Nanoparticles and
      Iron/Calcium Oxide and Cobalt/Calcium Oxide Nanocomposites.
AB  - We report an environmentally benign and cost-effective method to produce Fe and
      Co magnetic metal nanoparticles as well as the Fe/Cao and Co/CaO nanocomposites
      by using a novel, dry mechanochemical process. Mechanochemical milling of metal
      oxides with a suitable reducing agent resulted in the production of magnetic
      metal nanoparticles. The process involved grinding and consequent reduction of
      low-costing oxide powders, unlike conventional processing techniques involving
      metal salts or metal complexes. Calcium granules were used as the reducing agent.
      Magnetometry measurements were performed over a large range of temperatures, from
      10 to 1273 K, to evaluate the Curie temperature, blocking temperature,
      irreversibility temperature, saturation magnetization, and coercivity. The
      saturation magnetizations of the iron and cobalt nanoparticles were found to be
      191 and 102 emu g-1, respectively. The heating abilities of these nanoparticles
      suspended in several liquids under alternating magnetic fields were measured and
      the specific loss power was determined. Our results suggest that the dry
      mechanochemical process is a robust method to produce metallic nanoparticles and
      nanocomposites.

PMID- 30094126
TI  - Synthesis of Hollow Co-Fe Prussian Blue Analogue Cubes by using Silica Spheres as
      a Sacrificial Template.
AB  - Herein, we report a novel method for the formation of hollow Prussian blue
      analogue (CoFe-PBA) nanocubes, using spherical silica particles as sacrificial
      templates. In the first step, silica cores are coated by a CoFe-PBA shell and
      then removed by etching with hydrofluoric acid (HF). The cubic shape of CoFe-PBA
      is well-retained even after the removal of the silica cores, resulting in the
      formation of hollow CoFe-PBA cubes. The specific capacity of the hollow CoFe-PBA
      nanocubes electrodes is about two times higher than that of solid CoFe-PBA
      nanocubes as storage materials for sodium ions. Such an improvement in the
      electrochemical properties can be attributed to their hollow internal
      nanostructure. The hollow architecture can offer a larger interfacial area
      between the electrolyte and the electrode, leading to an improvement in the
      electrochemical activity. This strategy can be applied to develop PBAs with
      hollow interiors for a wide range of applications.

PMID- 30094127
TI  - Individual and environmental correlates of school-based recess engagement.
AB  - The purpose of this study was to examine individual variables associated with
      children's levels of recess physical activity (PA), as well as environmental
      influences that influence children's engagement during recess. Participants (n =
      146) were 4-6th grade students across seven schools. PA data were collected using
      the Fitbit Flex. Psychological need satisfaction at recess data were collected
      with a basic psychological need satisfaction for recess PA survey. Observations
      of recess activity engagement and the quality of the recess environment were also
      collected at 134 recess periods (n = 8340 children) across nine schools. Results
      of multi-level regression analyses indicated that gender and recess time were
      significant predictors of physical activity during recess. In examination of the
      environmental level factors, multi-level regression analyses revealed that 'adult
      engagement and supervision' was the only significant predictor for recess
      engagement in boys and girls. These findings suggest the amount of time
      allocated, and the quality of the recess environment must be included in
      evaluation of the critical factors relevant to engagement of students in
      physically active recesses.

PMID- 30094128
TI  - A case of pulmonary cryptococcoma due to Cryptococcus gattii in the United
      Kingdom.
AB  - We report a case of Cryptococcus gattii infection in the UK in a 76-year-old
      woman on biologic therapy for intra-abdominal non-Hodgkin lymphoma. An incidental
      nodular lung lesion was found on a chest imaging and histology, culture and
      molecular mycology studies of the lobectomy specimen revealed the presence of C.
      gattii.

PMID- 30094129
TI  - Incidental findings of blastomycosis lung nodules in five asymptomatic patients.
AB  - Asymptomatic blastomycosis infections are rarely identified or described in the
      literature, but are believed to comprise 50% of cases. In this report we describe
      five sporadic cases of blastomycosis in asymptomatic patients. All of these cases
      were initially identified as incidental findings of lung nodules on CXR or CT. To
      our knowledge, these are the first detailed descriptions of asymptomatic
      blastomycosis, occurring as sporadic disease, in the literature.

PMID- 30094130
TI  - T2Candida(r) to guide antifungal and lengh of treatment of candidemia in a
      pediatric multivisceral transplant recipient.
AB  - A case of 1-year- old male multivisceral transplant recipient with candidemia
      diagnosed by the T2Candida(r) test is presented. Optimal management of the
      candidemia complemented the treatment of the global clinical episode. Duration of
      treatment might be established much more precisely with the T2Candida(r) test
      than with blood cultures.

PMID- 30094131
TI  - Late-onset isavuconazole-induced liver injury.
AB  - Antifungal agents account for approximately 3% of Drug-Induced Liver Injury
      (DILI) cases. Isavuconazole is a novel triazole, and experience with long-term
      use of it is lacking. We report a case of late-onset DILI occurring after 11
      months of isavuconazole therapy in a 55-year old man of Angolan descent on long
      term antifungal therapy for the management of chronic pulmonary aspergillosis
      complicating previously treated pulmonary tuberculosis. The DILI could be
      described as idiosyncratic as it was not associated with high isavuconazole serum
      levels and his liver function tests returned to normal following treatment
      discontinuation.

PMID- 30094132
TI  - Bilateral Candida keratitis in an HIV patient with asymptomatic genitourinary
      candidiasis in Uganda.
AB  - A 35-year-old male presented with Candida keratitis in the left eye. He was HIV
      positive with a CD4 of 352 cells/uL. The eye quickly deteriorated, despite
      intensive antifungal treatment and was eviscerated. Five months later, he re
      presented with Candida keratitis in his right eye. A focal source of Candida
      infection was suspected and a urine culture identified Candida spp, despite being
      asymptomatic for genitourinary candidiasis. He was subsequently treated with good
      outcome (max. 75 words).

PMID- 30094133
TI  - Cutaneotrichosporon (Cryptococcus) cyanovorans, a basidiomycetous yeast, isolated
      from the airways of cystic fibrosis patients.
AB  - Cystic fibrosis (CF) patients are colonized with a multitude of bacteria and
      fungi. From respiratory samples of two CF patients in our institute, a difficult
      to identify yeast was isolated repeatedly. This yeast was eventually identified
      as Cutaneotrichosporon (Cryptococcus) cyanovorans by internal transcribed spacer
      (ITS) and ribosomal large subunit (LSU) sequencing. C. cyanovorans is a
      basidiomycetous yeast originally reported as environmental isolate from South
      African soil and has not been described before as clinical isolate from CF
      patients.

PMID- 30094134
TI  - Kodamaea ohmeri fungemia in severe burn: Case study and literature review.
AB  - Kodamaea ohmeri is a relatively rare yeast isolated form clinical specimens, and
      it is known to be a causative fungus of severe invasive infectious diseases in
      immunocompromised hosts. Herein, we describe fungemia due to K. ohmeri in a
      patient with a severe extended burn. The isolate was obtained from not only blood
      specimens but also skin lesions. We should be aware of risk for fungemia
      including K. ohmeri in case of severe burn.

PMID- 30094135
TI  - Donor-derived invasive aspergillosis after kidney transplant.
AB  - The risk of transmission of infectious diseases from allograft to recipient is
      well known. Viruses and bacteria are the most frequent causes of transmissible
      infections. Donor-derived invasive aspergillosis is rare and occurred under
      particular circumstances. We report 2 cases of kidney transplant recipients who
      acquired aspergillosis from a single donor.

PMID- 30094137
TI  - The West Point Knot: A Sliding-Locking Arthroscopic Knot.
AB  - Despite the advent of sutureless technology, knot tying remains an important
      skill for any arthroscopist. When one is choosing which knot to tie, there are a
      variety of options, with each possessing its own inherent strengths and
      weaknesses. The West Point knot is a sliding-locking arthroscopic knot that is
      relatively easy to learn and has excellent knot security. This article details
      the appropriate manner in which to tie this knot.

PMID- 30094136
TI  - Thermal effect of percutaneous radiofrequency ablation with a clustered electrode
      for vertebral tumors: In vitro and vivo experiments and clinical application.
AB  - Purpose: To investigate effects and heat distribution of radiofrequency ablation
      (RFA) on vertebral tumors in vitro and in vivo swine experiments and its clinical
      application. Materials and methods: RFA was performed on the swine spine in vitro
      and in vivo for 20 min at 90  degrees C at the electrode tip, and the temperature
      at the electrode tip and surrounding tissues were recorded. Clinical application
      of ablation combined with vertebroplasty was subsequently performed in 4 patients
      with spinal tumors. Results: In the in vitro study, the mean temperature at the
      front and ventral wall of the spinal canal was 50.8  degrees C and 43.6  degrees
      C, respectively, at 20 mm significantly greater than 37.7  degrees C and 33.7 +/-
      1.7  degrees C, respectively, at 10 mm ablation depth. The coagulative necrosis
      area was significantly (P < 0.0001) greater at 20 mm depth than at 10 mm depth
      (mean 17.0 * 20.7 mm2 vs. 14.2 * 16.6 mm2). In the in vivo experiment, the local
      temperature increased significantly (P < 0.05) from around 36  degrees C before
      ablation to over 41  degrees C at 20 min after ablation, with the temperature at
      the electrode tip (90.4  degrees C) and within the vertebral body (67.0  degrees
      C) significantly (P < 0.05) greater than at the posterior (41.9  degrees C) and
      lateral wall (41.8  degrees C). From 2 to 5 weeks, bone remodeling began.
      Clinically, all four patients had successful RFA and vertebroplasty, with no
      neurological deficits. The pain scores were significanlty (P < 0.05) improved
      before (4.5-10, mean 8.0) compared with at four weeks (0-1.8, mean 1.8).
      Conclusion: The clustered electrode can be efficiently and safely applied in the
      treatment of spinal tumors without damaging the spinal cord and adjacent nerves
      by heat distribution.

PMID- 30094138
TI  - Endoscopic Shelf Acetabuloplasty for Treating Acetabular Large Bone Cyst in
      Patient With Dysplasia.
AB  - Acetabular bone cyst is usually associated with dysplastic secondary
      osteoarthritis of the hip joint. Acetabular reorientation osteotomy is one of the
      most common therapeutic options for treating patients with hip dysplasia.
      However, it may be too invasive for athletes and can also lead to some
      complications including intraoperative fracture and postoperative bone necrosis
      especially in patients with acetabular large bone cysts. Endoscopic shelf
      acetabuloplasty offers a less invasive option for athletic patients with
      dysplasia of severity greater than those indicated for isolated hip arthroscopy.
      This Technical Note demonstrates endoscopic shelf acetabuloplasty with bone
      grafting, simultaneously addressing a large bone cyst and acetabular
      undercoverage, as part of a comprehensive approach addressing chondrolabral
      pathology while restoring capsular integrity in an athlete with moderate
      dysplasia.

PMID- 30094139
TI  - Using the Long Head of Biceps Tendon Autograft as an Anatomical Reconstruction of
      the Rotator Cable: An Arthroscopic Technique for Patients With Massive Rotator
      Cuff Tears.
AB  - The treatment of massive rotator cuff tears (MRCT) is challenging. Insufficient
      tissue quality, size, and retraction of the cuff often lead to failures of
      repair. Different techniques like direct repair, partial repair, and graft
      applications have been developed, but results are not yet predictable. In this
      arthroscopic technique the objective is not to reconstruct the rotator cuff as a
      tissue layer but to restore the biomechanical function of the rotator cable with
      an autograft of the long head of the biceps tendon. After glenohumeral
      inspection, the long head of the biceps tendon is harvested and the retracted
      cuff is released and, if possible, closed partially side-to-side. The biceps
      graft is positioned from the posterior aspect of the greater tubercle to the
      superior part of the lesser tubercle and fixed with 2 biotenodesis anchors.
      Finally, the cuff remnants are securely sutured to the biceps graft with standard
      cuff repair sutures. This arthroscopic technique has several advantages because
      the biceps autograft is easily harvested, autologous, and rich in collagen.
      Previous studies show use of the biceps tendon differently for reconstruction of
      the rotator cuff, with promising results. Future studies are needed to evaluate
      clinical outcomes.

PMID- 30094140
TI  - Elbow Arthroscopy for Treatment of Valgus Extension Overload.
AB  - Valgus extension overload syndrome (VEO) is the result of supraphysiologic
      stresses placed across the posterior elbow during pitching. Following failure of
      nonoperative measures, surgical options consist of arthroscopic or limited
      incision posteromedial decompression. Although technically challenging,
      arthroscopic treatment offers many advantages over open treatment, including
      improved joint visualization, decreased soft-tissue dissection, decreased
      postoperative pain, and quicker rehabilitation. Arthroscopic treatment of VEO
      consists of soft tissue and bony debridement, loose body removal, and osteophyte
      resection. This technique report details the steps of arthroscopic treatment of
      VEO in a patient with a subluxating ulnar nerve.

PMID- 30094141
TI  - Modified Latarjet Procedure Without Capsulolabral Repair for Failed Previous
      Operative Stabilizations.
AB  - The optimal management of recurrent anterior shoulder instability with
      significant glenoid bone loss continues to be a challenge. The high recurrence
      rates seen in arthroscopic Bankart repair in the presence of significant glenoid
      bone loss have led many surgeons to choose bony reconstructions to manage these
      injuries. The Latarjet procedure acts through the combination of 3 different
      mechanisms: the coracoid bone graft restores and extends the glenoid articular
      arc, the conjoint tendon acts as a dynamic sling on the inferior subscapularis
      and anteroinferior capsule when the arm is abducted and externally rotated, and
      the effect of repairing the capsule to the stump of the coracoacromial ligament.
      However, in patients with multiple recurrences and previous surgeries, the
      anteroinferior labrum and capsule are often very deficient or practically
      destroyed. This Technical Note provides a detailed description of the modified
      Latarjet procedure without capsulolabral repair for patients with failed previous
      operative stabilizations.

PMID- 30094142
TI  - Avoiding Neurological Complications of Elbow Arthroscopy.
AB  - Elbow arthroscopy is an increasingly common procedure performed in orthopaedic
      surgery. However, because of the presence of several major neurovascular
      structures in close proximity to the operative portals, it can have potentially
      devastating complications. The largest series of elbow arthroscopies to date
      described a 2.5% rate of postoperative neurological injury. All of these injuries
      were transient nerve injuries resolved without intervention. A recent report of
      major nerve injuries after elbow arthroscopy demonstrated that these injuries are
      likely under-reported in literature. Because of the surrounding neurovascular
      structures, familiarity with normal elbow anatomy and portals will decrease the
      risk of damaging important structures. The purpose of this Technical Note is to
      review important steps in performing elbow arthroscopy with an emphasis on
      avoiding neurovascular injury. With a sound understanding of the important bony
      anatomic landmarks, sensory nerves, and neurovascular structures, elbow
      arthroscopy can provide both diagnostic and therapeutic intervention with little
      morbidity.

PMID- 30094143
TI  - Application of a Beta-Tricalcium Phosphate Graft to Minimize Bony Defect in Bone
      Patella Tendon-Bone Anterior Cruciate Ligament Reconstruction.
AB  - Anterior cruciate ligament (ACL) reconstruction with a bone-patellar tendon-bone
      autograft yields good clinical outcomes. Despite appropriate clinical outcomes,
      the most common complaint after reconstruction with a bone-patellar tendon-bone
      autograft is anterior knee pain at the donor graft sites. Synthetic bone grafts,
      such as beta-tricalcium phosphate (beta-TCP), have been previously used to fill
      the bony defect in fractures as well as removal of bony tumors, and have shown
      positive utility in improving anterior knee pain after ACL reconstruction. In
      this Technical Note, we describe the technique of placing a beta-TCP graft in the
      donor graft site after bone-patellar tendon-bone ACL reconstruction. After
      standard arthroscopic ACL reconstruction, the beta-TCP is appropriately sized
      with an osteotome and sagital saw before being placed into the patellar and
      tibial donor sites. A 0-Vicryl suture is used to suture the periosteum to secure
      the beta-TCP graft at the donor sites. This described technique allows for
      appropriate sizing and secure placement of the graft to maximize bone
      regeneration at the donor site.

PMID- 30094144
TI  - "Over the Top" Augmentation for Partial Anterior Cruciate Ligament Tears Using
      Suspension Device for Tibial Fixation.
AB  - A technique for augmentation of the partial anterior cruciate ligament is
      presented. The patient is positioned supine with the knee flexed 90 degrees .
      After addressing intra-articular injuries, the autologous semitendinosus tendon
      is harvested and measured in a doubled manner; after that, the tibial tunnel is
      performed in the outside-in direction, of the same diameter of the doubled graft.
      Both ends of the graft are sutured together, after inserting it through the loop
      of a suspension device, which is attached in its augmentation piece. A lateral
      femoral incision is made, to approach the joint through the "over the top"
      position. A looped thread is introduced inside the joint with the aid of a hook.
      This thread pulls the graft's sutures through the "over the top" position. A
      femoral tunnel is then drilled in the lateromedial and caudocranial direction.
      The suspension device is attached to the anterior tibial cortex and the graft is
      pulled in the caudocranial direction to the femoral tunnel, where an interference
      screw is used for fixation.

PMID- 30094145
TI  - Posterior Glenohumeral Capsular Reconstruction Using an Acellular Dermal
      Allograft.
AB  - Posterior shoulder instability is an uncommon and challenging cause of shoulder
      pain and dysfunction. Surgical management has less reliable results and higher
      failure rates compared with techniques for anterior shoulder instability. The
      presence of generalized ligamentous laxity further complicates options for
      surgical management. If primary capsulolabral repair fails, controversy exists as
      to the optimal revision procedure. This technical description and video present
      an arthroscopic technique for reconstruction of the posterior glenohumeral
      capsule with an acellular dermal allograft to treat posterior instability in a
      patient with Ehlers-Danlos syndrome and a previously failed posterior capsular
      plication.

PMID- 30094146
TI  - Anterior Cruciate Ligament Repair Using Independent Suture Tape Reinforcement.
AB  - Recently there has been renewed interest in primary repair of the anterior
      cruciate ligament (ACL). Repair of the acute proximal ruptured ACL can be
      achieved with the independent suture tape reinforcement ACL repair technique. The
      independent suture tape reinforcement technique reinforces the ligament as a
      secondary stabilizer, encouraging natural healing of the ligament by protecting
      it during the healing phase and supporting early mobilization. The purpose of
      this article is to describe, with video illustration, this ACL repair technique.

PMID- 30094147
TI  - Suture Anchor Repair for a Medial Meniscus Posterior Root Tear Combined With
      Arthroscopic Meniscal Centralization and Open Wedge High Tibial Osteotomy.
AB  - Medial meniscus posterior root tear (MMPRT) is now attracting increased attention
      as a risk factor for the development of osteoarthritis. However, the healing rate
      after root repair by the suture anchor technique or the pull-out technique is
      still low. Here we report on a technique of MMPRT repair using suture anchor
      combined with arthroscopic meniscal centralization and open wedge high tibial
      osteotomy (OWHTO). The purposes of this technique are (1) to distribute the
      meniscal hoop tension between the root repair site and the centralization site
      and (2) to reduce the load on medial meniscus by OWHTO. The routine exposure for
      OWHTO with superficial medial collateral ligament release creates good
      visualization for arthroscopic root repair. The first anchor is inserted on the
      medial edge of the medial tibial plateau, and the second anchor is inserted on
      the root attachment through a posteromedial portal. After tying the knots, OWHTO
      could be performed without interference between the suture anchors and the screws
      of the plate for fixing the osteotomy. Although further follow-up is required,
      this technique could improve the outcomes after root repair, as well as have some
      technical advantages.

PMID- 30094148
TI  - Quantitative Arthroscopic Assessment of Articular Cartilage Quality by Means of
      Cartilage Electromechanical Properties.
AB  - Arthroscopic surgery has grown rapidly in recent decades. Despite accurately
      diagnosed clinical cases, the previous pain is retained in some patients after
      the operation, even though no visible chondral lesions are found during the
      procedure. A minimally invasive arthroscopic method of measuring articular
      cartilage electromechanical properties enables rapid and reliable intraoperative
      articular cartilage quality evaluation.

PMID- 30094149
TI  - Percutaneous Medial Ligament Reconstruction for Valgus Knee Instability.
AB  - Injuries to stabilizing elements on the medial side of the knee are one of the
      most common knee ailments. Because of the good healing capacity of these
      structures, acute injuries are typically treated conservatively. However, valgus
      laxity near full extension can persist in some patients. This laxity may be the
      source of instability due to medial joint space opening, which then requires
      surgical treatment. Various procedures have been described that aim to reproduce
      the anatomy of the medial collateral ligament (MCL) and the posterior oblique
      ligament (POL), which work together to stabilize the medial aspect of the knee.
      However, these are complex open surgical procedures, technically demanding to
      achieve the favorable isometry, which prevent joint contracture or recurrence of
      laxity. The purpose of this study was to describe a short construct that
      minimizes the risk of secondary loss of tension and complies with the principle
      of favorable anisometry. The graft is positioned in the joint opening axis,
      between the deep bundle of the MCL and the POL.

PMID- 30094150
TI  - Arthroscopic Remplissage Using a Double-Pulley System for Hill-Sachs Lesions for
      Recurrent Shoulder Instability.
AB  - Hills-Sachs lesions are bony lesions in the humeral head that occur as a result
      of an anterior shoulder dislocation. These lesions often happen in conjunction
      with tears of the labrum, and large, engaging lesions must be addressed in order
      to avoid recurrent instability. Moderate to large (>=3 mm deep) Hill-Sachs
      defects can be treated using arthroscopic remplissage to reduce the rotator cuff
      down into the lesion. We describe in this Technical Note and accompanying video
      an adaptation of the classic arthroscopic remplissage that uses a knotless double
      pulley technique with 2 suture anchors, which increases the footprint of
      fixation, reduces the technical difficulty of the procedure, and minimizes the
      number of portals that need to be made.

PMID- 30094151
TI  - Modified Shelf Acetabuloplasty Endoscopic Procedure With Allograft for
      Developmental Hip Dysplasia Treatment.
AB  - Hip dysplasia has been identified as one of the leading causes of osteoarthritis.
      However, hip arthroscopy alone, in the setting of hip dysplasia, remains
      controversial. In borderline hip dysplasia, with lateral center-edge angle (LCEA)
      between 18 degrees  and 25 degrees , good outcomes have been reported with
      appropriate capsular and labral management. However, in severe hip dysplasia,
      with LCEA below 18 degrees , there is an acetabular bony structural deficiency
      that must be addressed. Even with the potential benefit of hip arthroscopy in
      addressing intra-articular injuries related to the instability, it cannot be used
      for soft-tissue procedures. Periacetabular osteotomy remains the gold standard to
      address that matter; however, its invasive nature along with the long recovery
      time leaves some patients unwilling to undergo this procedure. New minimally
      invasive endoscopic procedures, derived from open techniques, describe acetabular
      autologous bone grafting as an alternative. Donor-side morbidity is always a
      concern when using autografts; we believe that the use of bone allograft will
      decrease this potential issue and make the procedure itself less invasive. This
      Technical Note will describe a type of endoscopic shelf acetabuloplasty using an
      allograft iliac bone graft.

PMID- 30094152
TI  - Endoscopic Release of the Piriformis Tendon and Sciatic Nerve Exploration by the
      Lateral Decubitus Approach Through an Incision on the Iliotibial Band.
AB  - Entrapment of the sciatic nerve is considered a challenging problem for
      orthopaedic surgeons. Many surgical interventions (open or endoscopic) have been
      described as treatments. We describe an endoscopic technique for release of the
      piriformis tendon and sciatic nerve exploration by the lateral approach through
      an incision on the iliotibial band.

PMID- 30094153
TI  - Isolated colonic metastasis two years after resection of stage IA primary
      adenocarcinoma of the lung: A case report.
AB  - Colonic metastasis from lung cancer is rare, generally asymptomatic and usually
      develop at advanced cancer stages. Here, we report a case with a resected stage
      IA lung adenocarcinoma in a 51yo male patient that presented two years later with
      mild abdominal pain due to intestinal obstruction caused by a metastatic colon
      tumor. The patient underwent colonoscopy followed by surgical resection and the
      pathologic report was adenocarcinoma which was the same as that from a lung
      nodule that was excised two years earlier. Immunohistochemistry was cytokeratin 7
      (CK7) positive, thyroid transcription factor 1 (TTF1) focally positive and
      cytokeratin 20 (CK20), caudal-related homeobox transcription factor 2 (CDX2)
      negative on both lung biopsy and colon surgical specimens. Interestingly there
      was no obvious lung cancer recurrence both at the time of metastasis and one year
      following chemotherapy.

PMID- 30094154
TI  - Papillary lung adenocarcinoma with psammomatous calcifications.
AB  - We present the case of a 71 y/o man with chronic obstructive pulmonary disease
      (COPD) who presented with 3 weeks of cough, phlegm, fever, and failed outpatient
      antibiotic therapy for pneumonia. CT of the chest showed unilateral interstitial
      changes and bronchoscopic biopsies demonstrated primary lung papillary
      adenocarcinoma and extensive concentric psammomatous calcifications.

PMID- 30094155
TI  - Recurrent diffuse lung disease due to surfactant protein C deficiency.
AB  - Surfactant protein C (SP-C) deficiency causes diffuse lung disease with variable
      prognosis and severity that usually presents in infancy. We present the case of a
      patient with diffuse lung disease who was successfully treated with
      hydroxychloroquine and steroids in infancy, who presented again as a young adult
      with respiratory symptoms. Exome sequencing identified a novel de novo SFTPC
      mutation (c.397A > C p.S133R). Mutated SP-C accumulates and leads to injury of
      alveolar type II cells, which normally replenish alveolar type I cells after
      injury. This may explain the symptom recurrence after lung injury in young
      adulthood. Although hydroxychloroquine has been hypothesized to interfere with
      mutated SP-C accumulation, data on long term outcome remains limited.

PMID- 30094156
TI  - Post-primary pulmonary TB haemoptysis - When there is more than meets the eye.
AB  - Haemoptysis is concerning for both patient and healthcare provider and points to
      the presence of severe underlying lung disease warranting investigation.
      Approximately 8% of patients with pulmonary tuberculosis (PTB) infection will
      experience haemoptysis at some point during their life [1;2]. The aetiology of
      haemoptysis in the setting of PTB is diverse and may occur during active or
      following prior PTB infection due to pulmonary complications. We describe the
      case of a 33-year-old female who presented with massive haemoptysis on two
      separate occasions within a five-month period. Her background history included
      PTB 6 years prior and subsequent post-TB bronchiectasis with a destroyed left
      lung, and the development of apical mycetoma's. Despite numerous pre-existing
      aetiologies that could account for haemoptysis in this patient, on this
      admission, a newly identified ruptured Rasmussen's aneurysm was identified by
      angiography and successfully treated with arterial embolization. This report
      serves to highlight the multitude of reasons for haemoptysis in a patient with
      post PTB lung destruction and the associated diagnostic challenges that may be
      present. In particular, we highlight the Rasmussen's aneurysm, a rare entity, as
      a hidden cause of haemoptysis, where despite extensive parenchymal lung disease
      identified on chest radiography, specialised imaging is needed to confirm the
      diagnosis.

PMID- 30094157
TI  - Multi-component relaxation in clinically isolated syndrome: Lesion myelination
      may predict multiple sclerosis conversion.
AB  - We performed a longitudinal case-control study on patients with clinically
      isolated syndrome (CIS) with the aid of quantitative whole-brain myelin imaging.
      The aim was (1) to parse early myelin decay and to break down its distribution
      pattern, and (2) to identify an imaging biomarker of the conversion into
      clinically definite Multiple Sclerosis (MS) based on in vivo measurable changes
      of myelination. Imaging and clinical data were collected immediately after the
      onset of first neurological symptoms and follow-up explorations were performed
      after 3, 6, and, 12 months. The multi-component Driven Equilibrium Single Pulse
      Observation of T1/T2 (mcDESPOT) was applied to obtain the volume fraction of
      myelin water (MWF) in different white matter (WM) regions at every time-point.
      This measure was subjected to further voxel-based analysis with the aid of a
      comparison of the normal distribution of myelination measures with an age and sex
      matched healthy control group. Both global and focal relative myelination content
      measures were retrieved. We found that (1) CIS patients at the first clinical
      episode suggestive of MS can be discriminated from healthy control WM conditions
      (p < 0.001) and therewith reproduced our earlier findings in late CIS, (2) that
      deficient myelination in the CIS group increased in T2 lesion depending on the
      presence of gadolinium enhancement (p < 0.05), and (3) that independently the CIS
      T2 lesion relative myelin content provided a risk estimate of the conversion to
      clinically definite MS (Odds Ratio 2.52). We initially hypothesized that normal
      appearing WM myelin loss may determine the severity of early disease and the
      subsequent risk of clinically definite MS development. However, in contrast we
      found that WM lesion myelin loss was pivotal for MS conversion. Regional
      myelination measures may thus play an important role in future clinical risk
      stratification.

PMID- 30094158
TI  - Disruption, emergence and lateralization of brain network hubs in mesial temporal
      lobe epilepsy.
AB  - Hubs of brain networks are brain regions exhibiting denser connections than
      others, promoting long-range communication. Studies suggested the reorganization
      of hubs in epilepsy. The patterns of connector hub abnormalities specific to
      mesial temporal lobe epilepsy (mTLE) are unclear. We wish to quantify connector
      hub abnormalities in mTLE and identify epilepsy-related resting state networks
      involving abnormal connector hubs. A recently developed sparsity-based analysis
      of reliable k-hubness (SPARK) allowed us to address this question by using
      resting state functional MRI in 20 mTLE patients and 17 healthy controls.
      Handling the multicollinearity of functional networks, SPARK measures a new
      metric of hubness by counting the number (k) of networks involved in each voxel,
      and identifies which networks are actually associated to each connector hub. This
      measure provides new information about the network architecture involving
      connector hubs and a realistic range of k-hubness. We quantified the disruption
      and emergence of connector hubs in individual epileptic subjects and assessed the
      lateralization of networks involving connector hubs. In mTLE, we found
      pathological disruptions of normal connector hubs in the mTL and within the
      default mode network. Right mTLE had remarkably higher emergence of new connector
      hubs in the mTL than left mTLE. Different patterns of lateralization of the
      salience network involving the abnormal hippocampus were found in right versus
      left mTLE. The temporal, cerebellar, default mode, subcortical and motor networks
      also contributed to the lateralization of hippocampal networks. We finally
      observed an asymmetrical connector hub reorganization and overall regularization
      of epilepsy-related resting state networks in mTLE, characterized by the
      disruption of distant connections and the emergence of local connections.

PMID- 30094160
TI  - Ketamine normalizes brain activity during emotionally valenced attentional
      processing in depression.
AB  - Background: An urgent need exists for faster-acting pharmacological treatments in
      major depressive disorder (MDD). The glutamatergic modulator ketamine has been
      shown to have rapid antidepressant effects, but much remains unknown about its
      mechanism of action. Functional MRI (fMRI) can be used to investigate how
      ketamine impacts brain activity during cognitive and emotional processing.
      Methods: This double-blind, placebo-controlled, crossover study of 33 unmedicated
      participants with MDD and 26 healthy controls (HCs) examined how ketamine
      affected fMRI activation during an attentional bias dot probe task with emotional
      face stimuli across multiple time points. A whole brain analysis was conducted to
      find regions with differential activation associated with group, drug session, or
      dot probe task-specific factors (emotional valence and congruency of stimuli).
      Results: A drug session by group interaction was observed in several brain
      regions, such that ketamine had opposite effects on brain activation in MDD
      versus HC participants. Additionally, there was a similar finding related to
      emotional valence (a drug session by group by emotion interaction) in a large
      cluster in the anterior cingulate and medial frontal cortex. Conclusions: The
      findings show a pattern of brain activity in MDD participants following ketamine
      infusion that is similar to activity observed in HCs after placebo. This suggests
      that ketamine may act as an antidepressant by normalizing brain function during
      emotionally valenced attentional processing. Clinical trial: NCT#00088699:
      https://www.clinicaltrials.gov/ct2/show/NCT00088699.

PMID- 30094159
TI  - Aberrant oscillatory dynamics during somatosensory processing in HIV-infected
      adults.
AB  - While the arrival of combination antiretroviral therapy significantly decreased
      the prevalence of HIV-associated dementia, between 35 and 70% of all infected
      adults continue to develop some form of cognitive impairment. These deficits
      appears to affect multiple neural subsystems, but the mechanisms and extent of
      damage are not fully understood. In the current study, we utilized
      magnetoencephalography (MEG), advanced oscillatory analysis methods, and a paired
      pulse somatosensory stimulation paradigm to interrogate pre-attentive inhibitory
      processing in 43 HIV-infected adults and 28 demographically-matched uninfected
      controls. MEG responses were imaged using a beamformer, and time series data were
      extracted from the peak voxel in grand-averaged functional brain images to
      quantify the dynamics of sensory gating, oscillatory power, spontaneous power,
      and other neural indices. We found a significantly weakened response to the
      second stimulation compared to the first across groups, indicating significant
      sensory gating irrespective of HIV-infection. Interestingly, HIV-infected
      participants exhibited reduced neural responses in the 20-75 Hz gamma range to
      each somatosensory stimulation compared to uninfected controls, and exhibited
      significant alterations in peak gamma frequency in response to the second
      stimulation. Finally, HIV-infected participants also had significantly stronger
      spontaneous activity in the gamma range (i.e., 20-75 Hz) during the baseline
      period before stimulation onset. In conclusion, while HIV-infected participants
      had the capacity to efficiently gate somatosensory input, their overall
      oscillatory responses were weaker, spontaneous baseline activity was stronger,
      and their response to the second stimulation had an altered peak gamma frequency.
      We propose that this pattern of deficits suggests dysfunction in the
      somatosensory cortices, which is potentially secondary to accelerated aging.

PMID- 30094161
TI  - Hippocampal functional connectivity is related to self-reported cognitive
      concerns in breast cancer patients undergoing adjuvant therapy.
AB  - Nearly three out of four survivors experience Cancer-Related Cognitive Impairment
      (CRCI) for months or years following treatment. Both clinical and animal studies
      point to the hippocampus as a likely brain region affected in CRCI, however no
      previous study has investigated the functional connectivity of the hippocampus in
      CRCI. We compared hippocampal connectivity in cancer survivors and healthy
      controls and tested the relationship between functional connectivity differences
      and measures of objective and subjective cognition. Exploratory analysis of
      inflammatory markers was conducted in a small subset of participants as well.
      FMRI data were acquired during a memory task from 16 breast cancer survivors and
      17 controls. The NIH Toolbox was used to assess cognitive performance and Neuro
      QoL was used to measure self-reported cognitive concerns. Whole-brain group-level
      comparisons identified clusters with different connectivity to the hippocampus in
      survivors versus controls during task. Average connectivity was extracted from
      clusters of significant difference between the groups and correlated with
      cognitive performance and subjective report. Survivors performed worse on a test
      of episodic memory and reported greater cognitive concern than controls.
      Exploratory analysis found higher IL6 in cancer survivors compared to controls.
      Cancer survivors demonstrated higher connectivity of hippocampus with left
      cuneus, left lingual, left precuneus, and right middle prefrontal gyrus compared
      with controls. In survivors, higher task-related hippocampal-cortical
      connectivity was related to worse subjective measures of cognitive concern. Of
      the four significant clusters, higher connectivity of the precuneus with
      hippocampus was significantly associated with worse cognitive concern in
      survivors. The observed greater hippocampal-cortical connectivity in survivors
      compared to controls is the first reported fMRI biomarker of subjective concern,
      and may represent a compensatory response to cancer and its treatments. This
      compensation could explain, in part, the subjective feelings of cognitive
      impairment that were reported by survivors.

PMID- 30094162
TI  - fMRI correlates of jumping-to-conclusions in patients with delusions:
      Connectivity patterns and effects of metacognitive training.
AB  - Background: Reasoning biases such as the jumping-to-conclusions bias (JTC) are
      thought to contribute to delusions. Interventions targeting these biases such as
      metacognitive training (MCT) may improve delusions. So far, it is not clear
      whether JTC depends on dopaminergic reward areas that constitute the main action
      locus of antipsychotic drugs, or on additional cortical areas. The present study
      aimed to investigate fMRI activation and functional connectivity patterns
      underlying JTC, and their changes following MCT, in patients with delusions.
      Methods: Participants were 25 healthy individuals and 26 patients with current
      delusions who were either medication-free or on stable medication without
      sufficient response. We assessed (1) BOLD activity in the task-positive (TPN),
      task-negative (TNN), and subcortical reward network (RN); (2) Psychophysiological
      interactions (PPI) of peak activation areas. Results: Presence of JTC
      (irrespective of group) was associated with lower RN activity during conclusion
      events, and with increased effective connectivity between TPN and TNN during draw
      events. Following MCT, changes were observed in TPN activity and in effective
      connectivity of inferior parietal cortex (part of the TPN) with all three target
      networks. Conclusion: JTC is associated not only with reward system areas that
      constitute the main target of antipsychotic drugs, but also with cortical areas,
      particularly of the TPN.

PMID- 30094164
TI  - Low-dose CT for the spatial normalization of PET images: A validation procedure
      for amyloid-PET semi-quantification.
AB  - The reference standard for spatial normalization of brain positron emission
      tomography (PET) images involves structural Magnetic Resonance Imaging (MRI)
      data. However, the lack of such structural information is fairly common in
      clinical settings. This might lead to lack of proper image quantification and to
      evaluation based only on visual ratings, which does not allow research studies or
      clinical trials based on quantification. PET/CT systems are widely available and
      CT normalization procedures need to be explored. Here we describe and validate a
      procedure for the spatial normalization of PET images based on the low-dose
      Computed Tomography (CT) images contextually acquired for attenuation correction
      in PET/CT systems. We included N = 34 subjects, spanning from cognitively normal
      to mild cognitive impairment and dementia, who underwent amyloid-PET/CT (18F
      Florbetaben) and structural MRI scans. The proposed pipeline is based on the
      SPM12 unified segmentation algorithm applied to low-dose CT images. The
      validation of the normalization pipeline focused on 1) statistical comparisons
      between regional and global 18F-Florbetaben-PET/CT standardized uptake value
      ratios (SUVrs) estimated from both CT-based and MRI-based normalized PET images
      (SUVrCT, SUVrMRI) and 2) estimation of the degrees of overlap between warped gray
      matter (GM) segmented maps derived from CT- and MRI-based spatial
      transformations. We found negligible deviations between regional and global SUVrs
      in the two CT and MRI-based methods. SUVrCT and SUVrMRI global uptake scores
      showed negligible differences (mean +/- sd 0.01 +/- 0.03). Notably, the CT- and
      MRI-based warped GM maps showed excellent overlap (90% within 1 mm). The proposed
      analysis pipeline, based on low-dose CT images, allows accurate spatial
      normalization and subsequent PET image quantification. A CT-based analytical
      pipeline could benefit both research and clinical practice, allowing the
      recruitment of larger samples and favoring clinical routine analysis.

PMID- 30094163
TI  - Short timescale abnormalities in the states of spontaneous synchrony in the
      functional neural networks in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a prevalent neurodegenerative condition that can lead
      to severe cognitive and functional deterioration. Functional magnetic resonance
      imaging (fMRI) revealed abnormalities in AD in intrinsic synchronization between
      spatially separate regions in the so-called default mode network (DMN) of the
      brain. To understand the relationship between this disruption in large-scale
      synchrony and the cognitive impairment in AD, it is critical to determine whether
      and how the deficit in the low frequency hemodynamic fluctuations recorded by
      fMRI translates to much faster timescales of memory and other cognitive
      processes. The present study employed magnetoencephalography (MEG) and a Hidden
      Markov Model (HMM) approach to estimate spontaneous synchrony variations in the
      functional neural networks with high temporal resolution. In a group of
      cognitively healthy (CH) older adults, we found transient (mean duration of 150
      250 ms) network activity states, which were visited in a rapid succession, and
      were characterized by spatially coordinated changes in the amplitude of source
      localized electrophysiological oscillations. The inferred states were similar to
      those previously observed in younger participants using MEG, and the estimated
      cortical source distributions of the state-specific activity resembled the
      classic functional neural networks, such as the DMN. In patients with AD,
      inferred network states were different from those of the CH group in short-scale
      timing and oscillatory features. The state of increased oscillatory amplitudes in
      the regions overlapping the DMN was visited less often in AD and for shorter
      periods of time, suggesting that spontaneous synchronization in this network was
      less likely and less stable in the patients. During the visits to this state, in
      some DMN nodes, the amplitude change in the higher-frequency (8-30 Hz)
      oscillations was less robust in the AD than CH group. These findings highlight
      relevance of studying short-scale temporal evolution of spontaneous activity in
      functional neural networks to understanding the AD pathophysiology. Capacity of
      flexible intrinsic synchronization in the DMN may be crucial for memory and other
      higher cognitive functions. Our analysis yielded metrics that quantify distinct
      features of the neural synchrony disorder in AD and may offer sensitive
      indicators of the neural network health for future investigations.

PMID- 30094166
TI  - Volume alteration of hippocampal subfields in first-episode antipsychotic-naive
      schizophrenia patients before and after acute antipsychotic treatment.
AB  - The nature of hippocampal changes in schizophrenia before first treatment, and
      whether hippocampal subfields are affected by antipsychotic treatment are
      important questions for schizophrenia research. Forty-one first-episode
      antipsychotic-naive acutely ill schizophrenia inpatients had MRI scans before and
      six weeks after antipsychotic treatment. Thirty-nine matched healthy controls
      were also scanned, twenty-two of which were scanned a second time six weeks
      later. Volumes of hippocampal subfields were measured via FreeSurfer v6.0 using a
      longitudinal analysis pipeline. Before treatment, schizophrenia patients had no
      significant changes in total hippocampal volume but exhibited significantly
      greater subfield volumes than controls in bilateral molecular layers of the
      hippocampus (ML), bilateral granular cell layers of the dentate gyrus (GC-DG),
      and bilateral cornu ammonis area 4 (CA4). After six weeks of antipsychotic
      treatment, patients showed volume reductions compared with pretreatment scans in
      total hippocampus bilaterally, with subfield volume reduction noted in previously
      enlarged subfields (i.e., bilateral ML, GC-DG and CA4) and in bilateral
      hippocampal tails, left CA1, CA3, and fimbria. Subfields with volume increases
      before treatment were reduced to the level of healthy controls (bilateral ML and
      GC-DG) or near to it (bilateral CA4) after treatment. These results indicate
      subfield-specific hippocampal hypertrophy prior to treatment, and that these
      abnormalities were reduced after acute antipsychotic therapy in a dose-related
      manner together with volume reductions in other areas that were not hypertrophic
      before treatment.

PMID- 30094165
TI  - Magnetic resonance markers of tissue damage related to connectivity disruption in
      multiple sclerosis.
AB  - Patients with multiple sclerosis (MS) display reduced structural connectivity
      among brain regions, but the pathogenic mechanisms underlying network disruption
      are still unknown. We aimed to investigate the association between the loss of
      diffusion-based structural connectivity, measured with graph theory metrics, and
      magnetic resonance (MR) markers of microstructural damage. Moreover, we evaluated
      the cognitive consequences of connectivity changes. We analysed the
      frontoparietal network in 102 MS participants and 25 healthy volunteers (HV). MR
      measures included radial diffusivity (RD), as marker of demyelination, and ratios
      of myo-inositol, N-acetylaspartate and glutamate+glutamine with creatine in white
      (WM) and grey matter as markers of astrogliosis, neuroaxonal integrity and
      glutamatergic neurotoxicity. Patients showed decreased global and local
      efficiency, and increased assortativity (p < 0.01) of the network, as well as
      increased RD and myo-inositol, and decreased N-acetylaspartate in WM compared
      with HV (p < 0.05). In patients, the age-adjusted OR of presenting abnormal
      global and local efficiency was increased for each increment of 0.01 points in RD
      and myo-inositol, while it was decreased for each increment of 0.01 points in N
      acetylaspartate (the increase of N-acetylaspartate reduced the risk of having
      abnormal connectivity), all in WM. In a multiple logistic regression analysis,
      the OR of presenting abnormal global efficiency was 0.95 (95% confidence
      interval, CI: 0.91-0.99, p = 0.011) for each 0.01 increase in N-acetylaspartate,
      and the OR of presenting abnormal local efficiency was 1.39 (95% CI: 1.14-1.71, p
      = 0.001) for each 0.01 increase in RD. Patients with abnormal efficiency had
      worse performance in attention, working memory and processing speed (p < 0.05).
      In conclusion, patients with MS exhibit decreased structural network efficiency
      driven by diffuse microstructural impairment of the WM, probably related to
      demyelination, astroglial and neuroaxonal damage. The accumulation of neuroaxonal
      pathological burden seems to magnify the risk of global network collapse, while
      demyelination may contribute to the regional disorganization. These network
      modifications have negative consequences on cognition.

PMID- 30094167
TI  - A functional limitation to the lower limbs affects the neural bases of motor
      imagery of gait.
AB  - Studies on athletes or neurological patients with motor disorders have shown a
      close link between motor experience and motor imagery skills. Here we evaluated
      whether a functional limitation due to a musculoskeletal disorder has an impact
      on the ability to mentally rehearse the motor patterns of walking, an overlearned
      and highly automatic behaviour. We assessed the behavioural performance (measured
      through mental chronometry tasks) and the neural signatures of motor imagery of
      gait in patients with chronic knee arthrosis and in age-matched, healthy
      controls. During fMRI, participants observed (i) stationary or (ii) moving videos
      of a path in a park shown in the first-person perspective: they were asked to
      imagine themselves (i) standing on or (ii) walking along the path, as if the
      camera were "their own eyes" (gait imagery (GI) task). In half of the trials,
      participants performed a dynamic gait imagery (DGI) task by combining foot
      movements with GI. Behavioural tests revealed a lower degree of isochrony between
      imagined and performed walking in the patients, indicating impairment in the
      ability to mentally rehearse gait motor patterns. Moreover, fMRI showed
      widespread hypoactivation during GI in motor planning (premotor and parietal)
      brain regions, the brainstem, and the cerebellum. Crucially, the performance of
      DGI had a modulatory effect on the patients and enhanced activation of the
      posterior parietal, brainstem, and cerebellar regions that the healthy controls
      recruited during the GI task. These findings show that functional limitations of
      peripheral origin may impact on gait motor representations, providing a rationale
      for cognitive rehabilitation protocols in patients with gait disorders of
      orthopaedic nature. The DGI task may be a suitable tool in this respect.

PMID- 30094169
TI  - Post-traumatic stress disorder and chronic hyperconnectivity in emotional
      processing.
AB  - Post-traumatic stress disorder (PTSD) is associated with heightened responses to
      threatening stimuli, particularly aggression-related emotional facial
      expressions. The stability over time of this neurophysiological 'hyperactive'
      threat response has not been determined. We studied implicit emotional face
      processing in soldiers with and without PTSD at two time-points (roughly 2 years
      apart) using magnetoencephalography to determine the response of oscillations and
      synchrony to happy and angry faces, and the reliability of this marker for PTSD
      over time. At the initial time-point we had 20 soldiers with and 25 without PTSD;
      35 returned for follow-up testing 2 years later, and included 13 with and 22
      without PTSD. A mixed-effects analysis was used. There were no significant
      differences (albeit a slight reduction) in the severity of PTSD between the two
      time-points. MEG contrasts of the neurophysiological networks involved in the
      processing of angry vs. happy faces showed that the PTSD group had elevated
      oscillatory connectivity for angry faces. Maladaptive hypersynchrony in PTSD for
      threatening faces was seen in subcortical regions, including the thalamus, as
      well as the ventromedial prefrontal cortex, cingulum gyri, inferior temporal and
      parietal regions. These results are generally consistent with prior studies and
      our own, and we demonstrate that this hyperconnectivity was stable over a two
      year period, in line with essentially stable symptomatology. Together, these
      results are consistent with the theory that hypervigilance in PTSD is driven by
      bottom-up, rapid processing of threat-related stimuli that engage a widespread
      network working in synchrony.

PMID- 30094168
TI  - Single-subject classification of presymptomatic frontotemporal dementia mutation
      carriers using multimodal MRI.
AB  - Background: Classification models based on magnetic resonance imaging (MRI) may
      aid early diagnosis of frontotemporal dementia (FTD) but have only been applied
      in established FTD cases. Detection of FTD patients in earlier disease stages,
      such as presymptomatic mutation carriers, may further advance early diagnosis and
      treatment. In this study, we aim to distinguish presymptomatic FTD mutation
      carriers from controls on an individual level using multimodal MRI-based
      classification. Methods: Anatomical MRI, diffusion tensor imaging (DTI) and
      resting-state functional MRI data were collected in 55 presymptomatic FTD
      mutation carriers (8 microtubule-associated protein Tau, 35 progranulin, and 12
      chromosome 9 open reading frame 72) and 48 familial controls. We calculated grey
      and white matter density features from anatomical MRI scans, diffusivity features
      from DTI, and functional connectivity features from resting-state functional MRI.
      These features were applied in a recently introduced multimodal behavioural
      variant FTD (bvFTD) classification model, and were subsequently used to train and
      test unimodal and multimodal carrier-control models. Classification performance
      was quantified using area under the receiver operator characteristic curves
      (AUC). Results: The bvFTD model was not able to separate presymptomatic carriers
      from controls beyond chance level (AUC = 0.570, p = 0.11). In contrast, one
      unimodal and several multimodal carrier-control models performed significantly
      better than chance level. The unimodal model included the radial diffusivity
      feature and had an AUC of 0.646 (p = 0.021). The best multimodal model combined
      radial diffusivity and white matter density features (AUC = 0.680, p = 0.005).
      Conclusions: FTD mutation carriers can be separated from controls with a modest
      AUC even before symptom-onset, using a newly created carrier-control
      classification model, while this was not possible using a recent bvFTD
      classification model. A multimodal MRI-based classification score may therefore
      be a useful biomarker to aid earlier FTD diagnosis. The exclusive selection of
      white matter features in the best performing model suggests that the earliest FTD
      related pathological processes occur in white matter.

PMID- 30094171
TI  - Type and timing of childhood maltreatment and reduced visual cortex volume in
      children and adolescents with reactive attachment disorder.
AB  - Reactive attachment disorder (RAD) is a severe social functioning disorder
      associated with early childhood maltreatment where the child displays emotionally
      withdrawn/inhibited behaviors toward caregivers. Brain regions develop at
      different rates and regions undergoing rapid change may be particularly
      vulnerable during these times to stressors or adverse experiences. The aim of
      this study was to investigate the effect of type and timing of childhood
      adversities on structural alterations in regional gray matter (GM) volume in
      maltreated children with RAD. High-resolution magnetic resonance imaging datasets
      were obtained for children and adolescents with RAD (n = 21; mean age = 12.76
      years) and typically developing (TD) control subjects (n = 22; mean age = 12.95
      years). Structural images were analyzed using a whole-brain voxel-based
      morphometry approach and the type and timing of maltreatment, which may be more
      strongly associated with structural alterations, was assessed using random forest
      regression with conditional inference trees. Our findings revealed that there is
      a potential sensitive period between 5 and 7 years of age for GM volume reduction
      of the left primary visual cortex (BA17) due to maltreatment. We also found that
      the number of types of maltreatment had the most significant effect on GM volume
      reduction and that the second most significant variable was exposure to neglect.
      The present study provides the first evidence showing that type and timing of
      maltreatment have an important role in inducing structural abnormalities in
      children and adolescents with RAD.

PMID- 30094170
TI  - Regional cortical thickness changes accompanying generalized tonic-clonic
      seizures.
AB  - Objective: Generalized tonic-clonic seizures are accompanied by cardiovascular
      and respiratory sequelae that threaten survival. The frequency of these seizures
      is a major risk factor for sudden unexpected death in epilepsy (SUDEP), a leading
      cause of untimely death in epilepsy. The circumstances accompanying such fatal
      events suggest a cardiovascular or respiratory failure induced by unknown neural
      processes rather than an inherent cardiac or lung deficiency. Certain cortical
      regions, especially the insular, cingulate, and orbitofrontal cortices, are key
      structures that integrate sensory input and influence diencephalic and brainstem
      regions regulating blood pressure, cardiac rhythm, and respiration; output from
      those cortical regions compromised by epilepsy-associated injury may lead to
      cardiorespiratory dysregulation. The aim here was to assess changes in cortical
      integrity, reflected as cortical thickness, relative to healthy controls.
      Cortical alterations in areas that influence cardiorespiratory action could
      contribute to SUDEP mechanisms. Methods: High-resolution T1-weighted images were
      collected with a 3.0-Tesla MRI scanner from 53 patients with generalized tonic
      clonic seizures (Mean age +/- SD: 37.1 +/- 12.6 years, 22 male) at Case Western
      Reserve University, University College London, and the University of California
      at Los Angeles. Control data included 530 healthy individuals (37.1 +/- 12.6
      years; 220 male) from UCLA and two open access databases (OASIS and IXI).
      Cortical thickness group differences were assessed at all non-cerebellar brain
      surface locations (P < 0.05 corrected). Results: Increased cortical thickness
      appeared in post-central gyri, insula, and subgenual, anterior, posterior, and
      isthmus cingulate cortices. Post-central gyri increases were greater in females,
      while males showed more extensive cingulate increases. Frontal and temporal
      cortex, lateral orbitofrontal, frontal pole, and lateral parietal and occipital
      cortices showed thinning. The extents of thickness changes were sex- and
      hemisphere-dependent, with only males exhibiting right-sided and posterior
      cingulate thickening, while females showed only left lateral orbitofrontal
      thinning. Regional cortical thickness showed modest correlations with seizure
      frequency, but not epilepsy duration. Significance: Cortical thickening and
      thinning occur in patients with generalized tonic-clonic seizures, in
      cardiovascular and somatosensory areas, with extent of changes sex- and
      hemisphere-dependent. The data show injury in key autonomic and respiratory
      cortical areas, which may contribute to dysfunctional cardiorespiratory patterns
      during seizures, as well as to longer-term SUDEP risk.

PMID- 30094172
TI  - Anxiety, depression, impulsivity, and brain structure in children and
      adolescents.
AB  - The unique neuroanatomical underpinnings of internalizing symptoms and
      impulsivity during childhood are not well understood. In this study, we examined
      associations of brain structure with anxiety, depression, and impulsivity in
      children and adolescents. Participants were 7- to 21-year-olds (N = 328) from the
      Pediatric Imaging, Neurocognition, and Genetics (PING) study who completed high
      resolution, 3-Tesla, T1-weighted MRI and self-report measures of anxiety,
      depression, and/or impulsivity. Cortical thickness and surface area were examined
      across cortical regions-of-interest (ROIs), and exploratory whole-brain analyses
      were also conducted. Gray matter volume (GMV) was examined in subcortical ROIs.
      When considered separately, higher depressive symptoms and impulsivity were each
      significantly associated with reduced cortical thickness in ventromedial
      PFC/medial OFC, but when considered simultaneously, only depressive symptoms
      remained significant. Higher impulsivity, but not depressive symptoms, was
      associated with reduced cortical thickness in the frontal pole, rostral middle
      frontal gyrus, and pars orbitalis. No differences were found for regional surface
      area. Higher depressive symptoms, but not impulsivity, were significantly
      associated with smaller hippocampal GMV and larger pallidal GMV. There were no
      significant associations between anxiety symptoms and brain structure. Depressive
      symptoms and impulsivity may be linked with cortical thinning in overlapping and
      distinct regions during childhood and adolescence.

PMID- 30094173
TI  - Lateral parietal contributions to memory impairment in posterior cortical
      atrophy.
AB  - Objective: Posterior cortical atrophy (PCA) is a neurodegenerative syndrome
      characterised by progressive impairment in visuospatial and perceptual function.
      Recent findings show that memory functioning can also be compromised early in the
      course of disease. In this study, we investigated the neural basis of memory
      impairment in PCA, and hypothesised that correlations would be observed with
      parietal cortex rather than classic medial temporal memory structures. Methods:
      Eighteen PCA patients, 15 typical Alzheimer's disease (tAD) patients and 21
      healthy controls underwent memory testing with the Rey Auditory Verbal Learning
      Test (RAVLT) word list and MRI. Voxel-based morphometry (VBM) was used to
      identify regions in the parietal and medial temporal lobes that correlated with
      memory performance. Results: Compared with controls, PCA patients were impaired
      at learning, immediate and delayed recall and recognition of the RAVLT. Learning
      rate and immediate recall was significantly better in PCA compared to tAD,
      whereas there was no difference in delayed recall. Recognition memory also was
      not statistically different between patient groups, but PCA patients made
      significantly more false positive errors than tAD patients. VBM analysis in the
      PCA patients revealed a significant correlation between total learning and grey
      matter density in the right supramarginal gyrus, right angular gyrus and left
      postcentral gyrus. The left post central gyrus also significantly correlated with
      immediate and delayed recall and with recognition memory. No correlations were
      detected in the medial temporal lobe. Conclusions: The findings provide novel
      evidence that early verbal memory impairment is frequently observed in PCA, and
      is associated with damage to lateral parietal structures. The results have
      implications for the diagnosis and management of PCA.

PMID- 30094174
TI  - Subdivisions of the posteromedial cortex in disorders of consciousness.
AB  - Evidence suggests that disruptions of the posteromedial cortex (PMC) and
      posteromedial corticothalamic connectivity contribute to disorders of
      consciousness (DOCs). While most previous studies treated the PMC as a whole,
      this structure is functionally heterogeneous. The present study investigated
      whether particular subdivisions of the PMC are specifically associated with DOCs.
      Participants were DOC patients, 21 vegetative state/unresponsive wakefulness
      syndrome (VS/UWS), 12 minimally conscious state (MCS), and 29 healthy controls.
      Individual PMC and thalamus were divided into distinct subdivisions by their
      fiber tractograpy to each other and default mode regions, and white matter
      integrity and brain activity between/within subdivisions were assessed. The
      thalamus was represented mainly in the dorsal and posterior portions of the PMC,
      and the white matter tracts connecting these subdivisions to the thalamus had
      less integrity in VS/UWS patients than in MCS patients and healthy controls. In
      addition, these tracts had less integrity in DOC patients who did not recover
      after 12 months than in patients who did. The structural substrates were
      validated by resting state fMRI finding impaired functional activity within these
      PMC subdivisions. This study is the first to show that tracts from dorsal and
      posterior subdivisions of the PMC to the thalamus contribute to DOCs.

PMID- 30094175
TI  - Morphological and molecular characterization of Cystoisospora sp. from Asian
      small-clawed otters Aonyx cinereus.
AB  - In this study, we provide the first description of Cystoisospora infection in
      Asian small-clawed otters (Aonyx cinereus). In July 2017, three juvenile otters
      recently imported from the Republic of Indonesia showed severe diarrhea and were
      diagnosed with coccidial infection; two of them eventually died. Fecal
      examination revealed the presence of numerous oocysts. Sporulated oocysts showed
      typical Cystoisospora features, measuring 24.6 +/- 1.6 (22.0-27.0) * 21.8 +/- 1.4
      (19.0-25.0) MUm, with an oocyst length/width ratio of 1.1 +/- 0.1 (1.0-1.3). Each
      sporocyst contained four sporozoites in a head-to-tail arrangement. The Stieda
      body was absent, and the sporocyst residuum was present. These morphological
      characteristics differentiated this species from the other valid Cystoisospora
      species described from mustelids. Molecular analysis was conducted at two loci:
      the nuclear 18S ribosomal RNA and mitochondrial cytochrome c oxidase subunit I
      genes. The 18S sequence showed high similarity with canine Cystoisispora
      ohioensis (1-bp difference, 1422/1423 [99.9%]). At the cytochrome c oxidase
      subunit I gene locus, the sequence from otters was identical to that of feline
      Cystoisospora rivolta (847/847 [100%]). Phylogenetic analyses using concatenated
      data demonstrated that Cystoisospora sp. from otters and C. rivolta grouped
      together in the same Cystoisospora clade. Based on these data, we concluded that
      Cystoisospora sp. detected from otters appeared to be highly similar to C.
      rivolta.

PMID- 30094176
TI  - Debilitating disease in a polyparasitised woylie (Bettongia penicillata): A
      diagnostic investigation.
AB  - During monitoring of critically endangered woylie (Bettongia penicillata)
      populations within the south-west of Western Australia, an adult female woylie
      was euthanased after being found in extremely poor body condition with diffuse
      alopecia, debilitating skin lesions and severe ectoparasite infestation.
      Trypanosoma copemani G2 and Sarcocystis sp. were detected molecularly within
      tissue samples collected post-mortem. Potorostrongylus woyliei and
      Paraustrostrongylus sp. nematodes were present within the stomach and small
      intestine, respectively. Blood collected ante-mortem revealed the presence of
      moderate hypomagnesaemia, mild hypokalaemia, mild hyperglobulinaemia and mild
      hypoalbuminaemia. Diffuse megakaryocytic hypoplasia was evident within the bone
      marrow. We propose various hypotheses that may explain the presence of severe
      ectoparasite infection, skin disease and poor body condition in this woylie.
      Given the potential deleterious effects of parasite infection, the importance of
      monitoring parasites cannot be over-emphasised.

PMID- 30094177
TI  - Transuterine infection by Baylisascaris transfuga: Neurological migration and
      fatal debilitation in sibling moose calves (Alces alces gigas) from Alaska.
AB  - Larval Baylisascaris nematodes (L3), resulting from transuterine infection and
      neural migration, were discovered in the cerebrum of sibling moose calves (Alces
      alces gigas) near 1-3 days in age from Alaska. We provide the first definitive
      identification, linking morphology, biogeography, and molecular phylogenetics, of
      Baylisascaris transfuga in naturally infected ungulates. Life history and
      involvement of paratenic hosts across a broader assemblage of mammals, from
      rodents to ungulates, in the transmission of B. transfuga remains undefined.
      Neural infections, debilitating young moose, may seasonally predispose calves to
      predation by brown bears, facilitating transmission to definitive hosts.
      Discovery of fatal neurological infections by L3 of B. transfuga in mammalian
      hosts serves to demonstrate the potential for zoonotic infection, as widely
      established for B. procyonis, in other regions and where raccoon definitive hosts
      are abundant. In zones of sympatry for multi-species assemblages of Baylisascaris
      across the Holarctic region presumptive identification of B. procyonis in cases
      of neurological larval migrans must be considered with caution. Diagnostics in
      neural and somatic larval migrans involving species of Baylisascaris in mammalian
      and other vertebrate hosts should include molecular-based and authoritative
      identification established in a phylogenetic context.

PMID- 30094179
TI  - Sign and magnitude scaling properties of heart rate fluctuations following vagus
      nerve stimulation in a patient with drug-resistant epilepsy.
AB  - Vagus nerve stimulation (VNS) therapy has been recently incorporated in Latin
      America as a treatment for drug-resistant epilepsy. In particular, it is known
      that linear analysis and fractal parameters of heart rate variability (HRV) are
      able to indirectly measure cardiac autonomic activity. This case report presents
      a 17-year-old female with drug-resistant epilepsy implanted with a VNS device. In
      order to explore cardiac autonomic changes due to VNS, linear and fractal HRV
      indices were calculated in the presence and absence of neurostimulation. Novel
      fractal scaling exponents from HRV analysis were obtained from this patient and
      from a healthy control subject. Our results indicate that fractal indices of HRV,
      such as short-term scaling parameters from magnitude and sign analyses seem to be
      sensitive to the presence or absence of VNS, being confirmed by linear classical
      methods. This study shows that VNS therapy increases the complexity of cardiac
      fluctuations in a patient with drug-resistant epilepsy, reflecting an augmented
      HRV non-linearity and a diminished anticorrelated pattern in heart rate
      fluctuations. A potential clinical use of these parameters includes the early
      identification of bradycardia, sudden unexpected death (SUDEP) risk and
      preoperative VNS approaches. Thus, the scaling and magnitude properties of HRV
      have potential importance as a non-invasive and easy method for adequate
      diagnostic/prognostic implications in epilepsy treatment.

PMID- 30094178
TI  - The wild world of Guinea Worms: A review of the genus Dracunculus in wildlife.
AB  - Nematodes are an extremely diverse and speciose group of parasites. Adult
      dracunculoid nematodes (Superfamily Dracunculoidea) occur in the tissues and
      serous cavities of mammals, fish, reptiles, amphibians and birds. Of the
      dracunculid group, perhaps best known is Dracunculus medinensis, the human Guinea
      Worm. Considerable work has been done on D. medinensis; however recent infections
      in peri-domestic dogs and the finding of naturally-infected paratenic hosts
      (previously unreported for D. medinensis) indicate we still have much to learn
      about these parasites. Furthermore, among eight species in the Old World and six
      species in the New World there is a lack of general life history knowledge as
      well as questions on species occurrence, host diversity, and transmission
      dynamics. Herein, we provide a comprehensive review of the genus Dracunculus, in
      order of a theoretical evolutionary progression from reptilian to mammalian
      hosts. Species descriptions, where available, are provided but also show where
      gaps occur in our knowledge of various species. Additionally, many first reports
      of Dracunculus spp. were done prior to the development and use of molecular
      tools. This is especially important for this group of parasites as speciation
      based on morphology is only applicable to males of the genus, and males, given
      their size, are notoriously difficult to recover from definitive hosts.
      Therefore, we also discuss current molecular tools used in the investigation of
      this group of parasites. Given recent host-switching events, the dracunculids are
      of increasing importance and require further work to expand our understanding of
      this genus.

PMID- 30094180
TI  - Working memory deficit in drug-resistant epilepsy with an amygdala lesion.
AB  - This study compared temporal lobe epilepsy (TLE) patients with amygdala lesion
      (AL) without hippocampal sclerosis (HS) (TLE-AL) with patients with TLE and HS
      without AL (TLE-HS). Both subtypes of TLE arose from the right hemisphere. The
      TLE-AL group exhibited a lower Working Memory Index (WMI) on the Wechsler Adult
      Intelligence Scale, third edition (WAIS-III), indicating that the amygdala in the
      right hemisphere is involved in memory-related function. [18F]fluorodeoxyglucose
      positron emission topography (FDG-PET) showed glucose hypometabolism limited to
      the right uncus for the TLE-AL group. The results suggest the importance of
      considering cognitive functions in the non-dominant hemisphere to prevent
      impairment after surgery.

PMID- 30094181
TI  - All osteoporotically deformed vertebrae with >34% height loss have
      radiographically identifiable endplate/cortex fracture.

PMID- 30094182
TI  - Axial and shear pullout forces of composite, porcine and human metatarsal and
      cuboid bones.
AB  - Objectives: The varying mechanical properties of human bone have influence on the
      study results. Pullout and shear forces of human bone were compared to different
      substitutes to evaluate their suitability for biomechanical studies. Methods:
      After bone mineral density (BMD) determination, axial pullout tests were
      performed with cortical 3.5 mm nonlocking (NL) and 2.7 mm head locking (HL)
      screws on human, porcine and polyurethane composite bones. Porcine and human
      constructs were additionally loaded in shear direction. Results: Apparent BMD was
      significantly lower in osteoporotic (159 mgHA/ccm +/- 56) and nonosteoporotic
      (229 mgHA/ccm +/- 25) human bone than that in porcine bone (325 mgHA/ccm +/- 42;
      p < 0.01). Axial construct stiffness and ultimate pullout force of porcine bone
      (NL: 666N/mm +/- 226, 910N +/- 140; HL: 309N/mm +/- 88, 744N +/- 185) was
      significantly different from composite bone (NL: 1284N/mm +/- 161; 1175N +/- 116;
      HL: 1241N/mm +/- 172, 1185N +/- 225) and osteoporotic human bone (NL: 204N/mm +/-
      121, 185N +/- 113; HL: 201N/mm +/- 65; 189N +/- 58) but not from nonosteoporotic
      human bone (NL: 620N/mm +/- 205, 852N +/- 281; HL: 399N/mm +/- 224; 567N +/-
      242). Porcine bone exhibited an ultimate shear force (NL: 278N +/- 99; HL: 431N
      +/- 155) comparable to nonosteoporotic human bone (NL: 207 +/- 68: HL: 374N +/-
      137). Conclusion: Screw pullout and shear forces of porcine bone are close to
      nonosteoporotic human bone. The translational potential of this article: Human
      bone specimens used in biomechanical studies are predominantly of osteoporotic
      bone quality. Conclusions on nonosteoporotic human bone behaviour are difficult.
      Alternatives such as porcine bone and composite bone were investigated, and it
      could be shown that screw pullout and screw shear forces of porcine bone are
      close to nonosteoporotic human bone.

PMID- 30094184
TI  - Double dose alglucosidase-alpha doubles benefit?

PMID- 30094183
TI  - Expanding the spectrum of PEX16 mutations and novel insights into disease
      mechanisms.
AB  - Zellweger syndrome spectrum disorders are caused by mutations in any of at least
      12 different PEX genes. This includes PEX16, an important regulator of peroxisome
      biogenesis. Using whole genome sequencing, we detected previously unreported,
      biallelic variants in PEX16 [NM_004813.2:c.658G>A, p.(Ala220Thr) and
      NM_004813.2:c.830G>A, p.(Arg277Gln)] in an individual with leukodystrophy,
      spastic paraplegia, cerebellar ataxia, and craniocervical dystonia with normal
      plasma very long chain fatty acids. Using olfactory-neurosphere derived cells, a
      population of neural stem cells, we showed patient cells had reduced peroxisome
      density and increased peroxisome size, replicating previously reported findings
      in PEX16 cell lines. Along with alterations in peroxisome morphology, patient
      cells also had impaired peroxisome function with reduced catalase activity.
      Furthermore, patient cells had reduced oxidative stress levels after exposure to
      hydrogen-peroxide (H2O2), which may be a result of compensation by H2O2
      metabolising enzymes other than catalase to preserve peroxisome-related cell
      functions. Our findings of impaired catalase activity and altered oxidative
      stress response are novel. Our study expands the phenotype of PEX16 mutations by
      including dystonia and provides further insights into the pathological mechanisms
      underlying PEX16-associated disorders. Additional studies of the full spectrum of
      peroxisomal dysfunction could improve our understanding of the mechanism
      underlying PEX16-associated disorders.

PMID- 30094185
TI  - Clinical and molecular characteristics of colombian patients with
      mucopolysaccharidosis IVA, and description of a new galns gene mutation.
AB  - A study published in 2012 estimated incidence of MPS IVA, in 0.68 cases per 100,
      000 live births in Colombia, and according to the Colombian Fund for High-Cost
      Diseases, in 2014 there were 15 people diagnosed with MPS IV. To enhance the
      knowledge of the disease in the country, we aimed to characterize clinical and
      molecular findings in 12 MPS IVA patients. Twelve patients were included in the
      study, with most patients of female gender (n = 7, 58,3%), age range 2 to 28
      years, average weight 26 kg (17.6-43 kg), average height 97 cm (92-104 cm),
      average BMI 27.6 kg/m2 (19.92-47.65 kg/m2). Clinical findings were similar to
      those described in the literature. GALNS gene molecular analysis showed five
      homozygous missense mutations in exon 11 c.1156C > T or p.R386C, a single
      nonsense mutation in the heterozygous state c.974G > A p.W325, and heterozygous
      in exon 9 mutation of exon 3 c.280C > T p.R94C, missense variant reported by
      Ogawa in 1995 [17]. There was only one patient that presented a homozygous
      missense mutation in exon 9 c.901G > T p.G301C and four patients showed the
      heterozygous form. A heterozygous missense mutation in exon 5 c.425A > T p.H142L,
      which has not been previously reported, was found in a female patient, 2 years 11
      months of age. The diagnosis algorithms that include molecular analysis,
      bioinformatic predictive tools, pharmacogenomics, and proteomics helps to improve
      the diagnosis, treatment, and prognosis of patients affected by MPS IVA.

PMID- 30094186
TI  - Morquio B patient/caregiver survey: First insight into the natural course of a
      rare GLB1 related condition.
AB  - Morquio B disease (MBD) or Mucopolysaccharidosis type IV B (MPS IV B) is caused
      by particular GLB1 mutations specifically affecting the affinity of beta
      galactosidase to keratan sulphate, resulting in dysostosis multiplex resembling
      Morquio A (MPS IV A) disease (GALNS deficiency). Additional neuronopathic
      features of GM1 II/III (juvenile/adult) gangliosidosis have been reported in some
      patients. Our patient/caregiver online survey was aimed at elucidating the
      clinical manifestations of this ultra-rare condition. Comparing to previously
      published data on MPS IV A, the 30 respondents in our MBD group presented with
      greater growth chart values (weight and height) and with lesser effects of
      odontoid hypoplasia. The most common concerns are: (1) mobility issues - 84%
      having difficulty walking; (2) chronic pain - 96%; (3) surgeries - average 3 per
      person, 80% for hip problems; (4) hip dysplasia, knee/ankle concerns, and
      scoliosis. Approximately 50% of MBD participants live independently and actively
      contributing to society. Evidence from our survey results supports the notion
      that skeletal manifestations in MBD are milder than in the majority of patients
      with MPS IV A. The data collected will help with the establishment of clinically
      meaningful outcomes for future therapeutic trials, and with the counseling of
      newly diagnosed patients about their health expectations.

PMID- 30094189
TI  - TRUS-guided needle drainage of a prostatic cyst for treatment of male
      infertility.

PMID- 30094187
TI  - A step closer in defining glycosylphosphatidylinositol anchored proteins role in
      health and glycosylation disorders.
AB  - Glycosylphosphatidylinositol anchored proteins (GPI-APs) represent a class of
      soluble proteins attached to the external leaflet of the plasma membrane by a
      post-translation modification, the GPI anchor. The 28 genes currently involved in
      the synthesis and remodelling of the GPI anchor add to the ever-growing class of
      congenital glycosylation disorders. Recent advances in next generation sequencing
      technology have led to the discovery of Mabry disease and CHIME syndrome genetic
      aetiology. Moreover, with each described mutation known phenotypes expand and new
      ones emerge without clear genotype-phenotype correlation. A protein database
      search was made for human GPI-APs with defined pathology to help building-up a
      physio-pathological mechanism from a clinical perspective. GPI-APs function in
      vitamin-B6 and folate transport, nucleotide metabolism and lipid homeostasis.
      Defining GPI-APs role in disease bears significant clinical implications.

PMID- 30094190
TI  - SGLT2 inhibitors and amputation risk: Real-world data from a diabetes foot wound
      clinic.

PMID- 30094188
TI  - Pathogenic and rare deleterious variants in multiple genes suggest oligogenic
      inheritance in recurrent exertional rhabdomyolysis.
AB  - Exertional rhabdomyolysis is a metabolic event characterized by the release of
      muscle content into the circulation due to exercise-driven breakdown of skeletal
      muscle. Recurrent exertional rhabdomyolysis has been associated with metabolic
      myopathies and mitochondrial disorders, a clinically and genetically
      heterogeneous group of predominantly autosomal recessive, monogenic conditions.
      Although genetics factors are well recognized in recurrent rhabdomyolysis, the
      underlying causes and mechanisms of exercise-driven muscle breakdown remain
      unknown in a substantial number of cases. We present clinical and genetic study
      results from seven adult male subjects with recurrent exertional rhabdomyolysis.
      In all subject, whole exome sequencing identified multiple heterozygous variants
      in genes associated with monogenic metabolic and/or mitochondrial disorders.
      These variants consisted of known pathogenic and/or new likely pathogenic
      variants in combination with other rare deleterious alleles. The presence of
      heterozygous pathogenic and rare deleterious variants in multiple genes suggests
      an oligogenic inheritance for exertional rhabdomyolysis etiology. Our data imply
      that exertional rhabdomyolysis can reflect cumulative effects or synergistic
      interactions of deleterious variants in multiple genes that are likely to
      compromise muscle metabolism under the stress of exercise.

PMID- 30094191
TI  - Evaluation of selenium nanoparticles and doxorubicin effect against
      hepatocellular carcinoma rat model cytogenetic toxicity and DNA damage.
AB  - The present study aimed to demonstrate the potent role of nanoselenium and
      Doxorubicin in retrogression of genotoxicity induced in hepatocellular carcinoma
      rat model by studying chromosomal aberration, micronuclei formation, DNA
      fragmentation as well as comet assay. Male rats hepatocellular carcinoma model
      were treated with Se-Nanoparticles, Doxurobicin (DOX) and the combination of
      both. The results revealed the protective effect of nanoselenium, Doxorubicin and
      their combination on bone marrow cytogenetic toxicity by decreasing chromosomal
      aberrations and micronuclei formation as well as their effects on rat's liver by
      decreasing DNA damage. Nevertheless, the treatment with nanoselenium either alone
      or in combination with Doxorubicin was more effective than treatment with
      doxorubicin alone.

PMID- 30094192
TI  - Microsurgical sequestectomy at 36 weeks of pregnancy: A case report.
AB  - About 30% of pregnant women experience lower back pain. The cause is usually
      increased mechanical stress combined with the ligament laxity induced by relaxin.
      Rarely, lower back pain is related to disc herniation. We report such a case,
      where microsurgical sequestectomy was performed at 36 weeks and three days of
      gestation because of severe extensor paresis of the left foot and big toe. The
      case shows that microsurgical treatment during pregnancy is safe. After treatment
      the patient regained full motor function and her pain regressed. She had a
      spontaneous vaginal delivery at 38 weeks.

PMID- 30094193
TI  - Superior vena cava syndrome related to mediastinal lymphoma in late pregnancy: A
      case report.
AB  - We report the initial diagnosis in a 28-year-old nulliparous woman of a primary
      mediastinal B-cell lymphoma in late pregnancy. For several weeks the patient had
      had symptoms of mediastinal obstruction, such as dyspnea, cough, swelling of the
      face and upper limbs. However, these symptoms had been misattributed to the
      pregnancy and a common cold. Due to a rapid decline in the patient's
      cardiovascular performance, she was transferred to the closest perinatal center
      in the 34th week of pregnancy, whereupon a cesarean section was performed. The
      diagnosis of a primary mediastinal B-cell lymphoma was made postpartum from a
      biopsy. This case emphasizes the importance of timely antenatal investigation in
      pregnant women with symptoms consistent with mediastinal obstruction. Thoracic
      ultrasonography can be a valuable tool for the detection of tumor-associated
      pleural and pericardial effusions.

PMID- 30094195
TI  - Ruptured ectopic pregnancy following a cycle of freeze-all in vitro
      fertilization: A case report.
AB  - Patients undergoing assisted reproduction are advised to abstain from intercourse
      to prevent the possibility of multiple pregnancy. If patients do not follow this
      advice, multiple dizygotic pregnancy or even a heterotopic pregnancy can result.
      We report the case of a 28-year-old nulliparous female with unexplained
      infertility who underwent freeze-all vaginal oocyte retrieval. Twenty-one days
      later she presented with vaginal bleeding (similar to menstruation) and right
      lower-quadrant pain. The results of ultrasound scanning and a laboratory work-up
      were consistent with an ectopic pregnancy. She underwent laparoscopic right
      salpingectomy for a tubal ectopic pregnancy. We recommend sexual abstinence
      during assisted reproduction to lower the risk of multiple pregnancy and
      especially of heterotopic pregnancy.

PMID- 30094194
TI  - Rupture of a myomectomy site in the third trimester of pregnancy after
      myomectomy, septoplasty and cesarean section: A case report.
AB  - Uterine rupture during pregnancy is a rare but dangerous complication. A history
      of cesarean section is known to be a risk factor, but other types of uterine
      surgery can also increase the risk. We report a case of rupture of a myomectomy
      site in the third trimester of pregnancy without uterine contractions in a woman
      who had previously undergone myomectomy, septoplasty and cesarean section. The 39
      year-old woman (gravida 2, para 2) presented at 29 weeks' gestation with uterine
      contractions. She was successfully treated with tocolytics. At 32 weeks of
      pregnancy, in the absence of contractions, the patient complained of severe
      abdominal pain and she became hypotensive. Emergency laparotomy and cesarean
      section were performed, resulting in the delivery of a live infant. The
      myomectomy site was found to have ruptured but the cesarean and septoplasty scars
      were intact. This case suggests that myomectomy scars are at greater risk of
      rupture during pregnancy than those resulting from cesarean section and
      septoplasty.

PMID- 30094196
TI  - Angular vs. interstitial pregnancy: A case report highlighting diagnostic nuances
      with stark management differences.
AB  - Background: In the literature, the terms "angular", "interstitial" and "cornual"
      have often been inappropriately interchanged. The consequence is under
      recognition of their differences as well as inaccurate imaging guidelines which
      do not reliably distinguish them as distinct entities. Angular pregnancies should
      be considered viable and may be managed to term. Case: A woman at 7w5d was
      transferred for surgical management of a presumed interstitial ectopic pregnancy.
      Sonography and MRI confirmed an eccentric fundal pregnancy with a thin myometrial
      mantle of 2-5 mm; the diagnosis of interstitial pregnancy was favored. Upon
      laparoscopy, the round ligament was displaced lateral to the pregnancy bulge and
      the diagnosis of angular pregnancy was thus apparent. The pregnancy was continued
      to term and delivered via repeat cesarean section without incident. Conclusion:
      Angular and interstitial pregnancies are different entities which cannot always
      be reliably distinguished via imaging alone. Diagnostic laparoscopy may be a
      final step in determining pregnancy location. Angular pregnancies should be
      considered potentially viable and may be managed to term.

PMID- 30094197
TI  - Case report on rhabdomyolysis after minimally invasive surgery for squamous cell
      carcinoma of the uterine cervix and adhesions due to deep infiltrating
      endometriosis.
AB  - Rhabdomyolysis is a rare clinical condition resulting from severe muscle damage
      that can cause potentially life-threatening complications. Amongst other causes,
      muscle compression due to patient positioning during prolonged surgery may result
      in extensive skeletal muscle breakdown. We report on a 39-year-old nulligravida
      who developed rhabdomyolysis after prolonged laparoscopic surgery for cervical
      cancer and adhesions due to deep infiltrating endometriosis. Minimally invasive
      surgical procedures offer major advantages in gynecologic cancer surgery, and
      preventive methods provide effective pressure reduction and play a crucial role
      in avoiding physical harm after surgical positioning. Nevertheless, a combination
      of surgical and patient-related risk factors may increase the risk of
      postsurgical onset of rhabdomyolysis. Immediate referral to a specialist center
      is necessary to ensure prevention of serious complications.

PMID- 30094198
TI  - Prenatal diagnosis of fetal cardiac rhabdomyoma associated with tuberous
      sclerosis: A case report.
AB  - Cardiac tumors are rarely diagnosed in utero. Rhabdomyomas are the most common
      fetal cardiac tumors. They are usually diagnosed during the first year of life
      after obstruction of a valve orifice or a cardiac chamber; but they can be
      detected by echocardiography as early as the second trimester. Rhabdomyomas are
      usually small. Fetal hydrops and pericardial effusion are rare. The most
      important indication of tuberous sclerosis in the prenatal period is cardiac
      rhabdomyoma. Early diagnosis of cardiac rhabdomyoma is thus important for early
      diagnosis of tuberous sclerosis. This case report concerns the prenatal diagnosis
      of both multiple fetal cardiac rhabdomyomas and tuberous sclerosis.

PMID- 30094199
TI  - Treatment-refractory vulvodynia from nutcracker syndrome: A case report.
AB  - Background: Pelvic venous disorders are often undiagnosed due to the symptom
      variability and similarity to other disease presentations. 'Pelvic congestion
      syndrome' is a term often used as a diagnosis of exclusion, since there is
      currently no standardized diagnostic approach for pelvic venous disorders, which
      further delays treatment. Case: A 25-year-old woman with treatment-refractory
      vulvodynia presented with symptoms that included left-sided vaginal wall pain,
      pruritis, dysmenorrhea, dyspareunia, muscle tension, and a chronic vaginal
      ulceration. Abnormal pelvic varices were discovered, and she was referred to
      vascular surgery for treatment of nutcracker syndrome causing ovarian vein reflux
      and abnormal engorgement of pelvic varices. Conclusion: Patients presenting with
      signs of pelvic venous insufficiency such as vaginal pruritis, irritation, pain,
      recurrent vaginitis, or chronic ulcerations should be examined for pelvic venous
      disorders.

PMID- 30094200
TI  - A practical method to control spatiotemporal confounding in environmental impact
      studies.
AB  - Separating natural spatiotemporal variation from the impact of human activities
      has long been a challenge in environmental impact studies. To overcome this
      problem, a causal modelling method based on spatiotemporal data, integrated with
      existing statistical methods such as multivariate redundancy analysis, multiple
      regression and, ordination was used for inferring causal effects of wastewater on
      biotic ecosystems. The causal modelling techniques were structural equation
      modelling (SEM) and Bayesian Networks (BNs); SEM, with the help of statistical
      analysis, was used for building deterministic models while the composite
      hypothesis underlying the models was checked based on the principle of BNs. Both
      spatial and temporal variations were considered in the design of the study so
      that spatiotemporal confounding could be controlled by adjusting for 'time' and
      'distance' in the models. This improved the external validity of the models, so
      they could be used for predicting the effect of interventions, e.g. manipulating
      the discharge loads. This could be possible where time-varying variables such as
      quantity of discharge effluent were included in the models. Models can be used
      for prediction the effect of an intervention in situations understood as causal.
      Thus, the causal structure of composite hypotheses of the study was tested using
      both local and global tests.

PMID- 30094201
TI  - Feldspar flotation as a quartz-purification method in cosmogenic nuclide dating:
      A case study of fluvial sediments from the Pamir.
AB  - Cosmogenic nuclide (CN) dating relies on specific target minerals such as quartz
      as markers to identify geologic events, including the timing of landscape
      evolution. The presence of feldspar in sediment samples poses a challenge to the
      separation of quartz and affects the chemical procedures for extracting the
      radioactive CNs 10Be and 26Al. Additionally, feldspar contamination reduces the
      26Al/27Al ratio, thus hinders the accurate determination of 26Al by accelerator
      mass spectrometry (AMS). Using fluvial sediment samples from Central Asia, which
      contain 16-50 weight percent (wt.%) of feldspar, we show that the standard
      physical separation and chemical cleaning-up procedures for quartz-enrichment
      reduces the feldspar content to only 9-47 wt.%. We present a new froth flotation
      mineral-separation device and procedure that allows for very effective quartz
      enrichment before CN chemistry. Our flotation cell, which has a volume of 600
      cm3, is built of borosilicate glass, holds up to 90 g of sample, and achieves
      quartz and feldspar separation in <=2 h for very feldspar-rich samples. We trace
      the stepwise enrichment of quartz to 95-100% purity with our procedure by X-ray
      diffraction analysis.

PMID- 30094202
TI  - Determining the distribution of granule diameter from biological sludge.
AB  - Anaerobic granule sizes from various types of anaerobic biological wastewater
      treatments were investigated in order to understand the influence of this
      characteristic on the performance of the treatment system. To date, there is no
      standardised methodology in the current literature, which provides details of a
      process to obtain data, such as a suitable sample volume, a description of the
      precision and limitations of the techniques used. Therefore, the aim of this
      protocol is to standardise the granulometry assay that can measure granule sizes
      accurately and quickly. In addition, the proposed methodology comprises about
      1500-3000 granules in a single sample, a representative number compared to the
      currently applied methodologies.

PMID- 30094203
TI  - One-phase phenol-free method for microRNA isolation from blood plasma.
AB  - MicroRNA extraction is an essential procedure when discovering MicroRNA-based
      biomarkers and approaches. Here we describe a new method for microRNA isolation
      from human blood plasma, based on isopropanol precipitation from the one-phase
      lysate. We demonstrate that the use of more than four volumes of lysis buffer
      based on 5 M guanidine isothiocyanate prevents the formation of large, viscous,
      and hardly soluble precipitate. Applying widely used linear polyacrylamide (LPAA)
      as the only precipitating agent proved ineffective. At the same time, adding
      poly(A)RNA or tRNA with LPAA significantly increased the amount of microRNA
      obtained. Replacing beta-mercaptoethanol with less volatile dithiothreitol in
      lysis buffer did not lead to a decrease in the yield. We compared the method
      proposed with miRNeasy Mini Kit (Qiagen) for isolation of microRNA from human
      blood plasma. MicroRNA yield was evaluated by the difference in median Ct values
      obtained for exogenous cel-238 and endogenous microRNA-21 cDNA amplification. For
      both tested microRNA, the precipitation from one-phase lysate provided better
      recovery with lower Ct values (Delta median Ct 4.94 for cel-238, r = 1,0E-04 and
      Delta median Ct 2.18 for microRNA-21, r = 9,0E-04). Thus, the method we described
      showed high yield and operating convenience because it can be applied without
      special equipment.

PMID- 30094204
TI  - A unifying framework for fast randomization of ecological networks with fixed
      (node) degrees.
AB  - The Curveball algorithm is an efficient and unbiased procedure for randomizing
      bipartite networks (or their matrix counterpart) while preserving node degrees.
      Here we introduce two extensions of the procedure, making it capable to randomize
      also unimode directed and undirected networks. We provide formal mathematical
      proofs that the two extensions, as the original Curveball, are fast and unbiased
      (i.e. they sample uniformly from the universe of possible network
      configurations).

PMID- 30094205
TI  - Optimized alamarBlue assay protocol for drug dose-response determination of 3D
      tumor spheroids.
AB  - The assessment of drug-dose responses is vital for the prediction of unwanted
      toxicological effects in modern medicine. Three-dimensional (3D) cell cultures
      techniques can provide in vivo-like spheroids and microtissues that resemble
      natural tumor function. However, formation of necrotic core and diffusion
      limitation of chemical compounds within these models can reduce the
      reproducibility and precision of standard bioassay protocols used to test two
      dimensional (2D) cell cultures. Nonetheless, the accurate prediction of
      detrimental effects of test compounds based on functional bioassays is essential
      for the development of new efficient therapeutic strategies. For instance,
      alamarBlue(r) is a widely-used commercially available redox indicator dye that
      can evaluate metabolic activity and cellular health status in a single-step
      procedure however, suitability and optimization of this bioassay must be
      determined for each individual application scenario. Here, we optimized the
      standard alamarBlue(r) proliferation/viability protocol for tumor spheroid
      cultures to enhance assay precision during toxicological drug screening. We
      optimized the original protocol of alamarBlue(r) assay that usually suggests an
      incubation time of 2-4 hours. The key modifications of the protocol for spheroid
      cultures are as follows: *Aspiration of cell culture medium before drug
      exposure.*Replacement of drug-supplemented medium with 10% (v/v) alamarBlue(r)
      reagent mixed with culture medium.*Increase of incubation period to 24 h at 37 
      degrees C protected from light.

PMID- 30094206
TI  - An optimized method for the bio-harvesting of microalgae, Botryococcus braunii,
      using Aspergillus sp. in large-scale studies.
AB  - The use of fossil fuels which are derived from non-renewable sources has been
      linked to global warming, adverse human health effects and environmental
      pollution. Consequently, there is a need to develop alternative sources of fuel
      that are renewable and more environment-friendly. Biofuel (biodiesel), produced
      from microalgae such as Botryococcus braunii is an alternative energy source,
      that is renewable (because algae can be cultured as needed), more biodegradable
      with lower global warming potential compared to fossil fuels. However, the use of
      microalgae is hampered by high costs associated with the production and
      harvesting of microalgal biomass in large-scale studies. In this article; *A
      robust and cost-effective method was developed for harvesting B.
      braunii*Optimized Aspergillus sp.: B. braunii ratio (1:40) was used to bio
      flocculate up to 97% of cultured microalgae in both small and large-scale studies
      (250 L)*No damage to the harvested microalgal biomass (validated by pyrolysis)
      was observed with the harvested biomass being suitable for any desired downstream
      application.

PMID- 30094207
TI  - Ruthenium nanoparticles stabilized by mercaptan and acetylene derivatives with
      supercapacitor application.
AB  - Ruthenium nanoparticles (RuHT, RuPET and RuPA) were prepared by hydrazine hydrate
      reduction of RuCl3 and stabilized by the self-assembly of organic molecules
      (hexanethiol, phenylethanethiol and phenylacetylene). The sizes of these Ru
      nanoparticles were carried out by transmission electron microscopic measurement,
      with the average core sizes of 2.84 +/- 0.55 nm, 3.06 +/- 1.22 nm, and 3.10 +/-
      1.08 nm, respectively. The structures and properties of these Ru nanoparticles
      were further examined and verified by UV-vis, FTIR, 1HNMR, XPS and fluorescent
      measurements. The performance of the supercapacitor was characterized by cyclic
      voltammetry and constant-current charge-discharge analysis. Ru nanoparticles
      exhibited enhanced supercapacitor behaviors as compared with blank electrodes.
      The Ru nanoparticles for supercapacitors in the H2SO4 electrolyte exhibited areal
      capacitances of 347.8, 304.9 and 229.1 mF cm-2 for RuPET, RuPA and RuHT at a scan
      rate of 10 mV s-1, and specific capacitances for 344.4, 249.3, 230.0 F g-1 for
      RuPET, RuPA and RuHT at a current density of 0.5 A g-1, respectively. The
      interfacial bonding between ruthenium and the outlayer organic ligands and varied
      ratio of ruthenium in high valence might be the reasonable explanation for the
      capacitance difference.

PMID- 30094208
TI  - Cloning and characterization of a chitinase from Thermobifida fusca reveals
      Tfu_0580 as a thermostable and acidic endochitinase.
AB  - Being capable of hydrolyzing chitin, chitinases have various applications such as
      production of N-acetylchitooligosaccharides (COSs) and N-acetylglucosamine
      (GlcNAc), degrading chitin as a consolidated bioprocessing, and bio-control of
      fungal phytopathogens. Here, a putative chitinase in Thermobifida fusca,
      Tfu_0580, is characterized. Tfu_0580 was purified by homogeneity with a molecular
      weight of 44.9 kDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis
      (SDS-PAGE) analysis. Tfu_0580 displayed a clear activity against colloidal
      chitin, which is comparable to a commercial Streptomyces griseus chitinase.
      Enzyme activities against p-nitrophenyl beta-D-N,N',N''-triacetylchitotriose (p
      NP-(GlcNAc)3), N,N'-diacetyl-beta-D-chitobioside (p-NP-(GlcNAc)2) and p
      nitrophenyl N-acetyl-beta-D-glucosaminide (p-NP-(GlcNAc)) showed that Tfu_0580
      exhibited highest activity against p-NP-(GlcNAc)3. Further optimization of the
      enzyme activity conditions showed: 1) an optimum catalytic activity at pH 6.0 and
      30  degrees C; 2) activity over broad pH (4.8-7.5) and temperature (20-55 
      degrees C); 3) stimulation of activity by the metallic ions Ca2+ and Mn2+.

PMID- 30094209
TI  - Percutaneous coronary intervention versus coronary bypass surgery for unprotected
      left main disease: a meta-analysis of randomized controlled trials.
AB  - Background: This meta-analysis of randomized controlled trials (RCTs) was aimed
      at comparing coronary artery bypass grafting (CABG) with percutaneous coronary
      intervention (PCI) for the treatment of unprotected left main coronary disease.
      Methods: All RCTs randomizing patients to any type of PCI with stents vs. CABG
      for left main disease (LMD) were included. Primary outcome was a composite of
      follow-up death/myocardial infarction/stroke/repeat revascularization. Secondary
      outcomes were peri-procedural mortality and the individual components of the
      primary outcome. Incidence rate ratio (IRR) or odds ratio (OR) and 95% confidence
      intervals (CIs) were pooled using a generic inverse variance method with random
      effects model. Subgroup analyses were done based on: (I) type of PCI [bare metal
      stents (BMS) vs. drug-eluting stents (DES)] and; (II) mean SYNTAX score tertiles.
      Leave one-out analysis and meta-regression were performed. Results: Six trials
      were included (4,700 patients; 2,349 PCI and 2,351 CABG). Follow-up ranged from
      2.33 to 5 years. PCI was associated with higher risk of follow-up
      death/myocardial infarction/stroke/repeat revascularization (IRR =1.328, 95% CI,
      1.114-1.582, P=0.002) and of repeated revascularization (IRR =1.754, 95% CI,
      1.470-2.093, P<0.001). The risk of peri-procedural mortality (OR =0.866, 95% CI,
      0.460-1.628, P=0.654), follow-up mortality (IRR =0.947, 95% CI, 0.711-1.262,
      P=0.712), myocardial infarction (IRR =1.342, 95% CI, 0.827-2.179, P=0.234) and
      stroke (IRR =0.800, 95% CI, 0.374-1.710, P=0.565) were similar between groups. No
      differences were found between DES and BMS subgroups. The risk of follow-up
      death/myocardial infarction/stroke/repeat revascularization with PCI was higher
      in all SYNTAX tertiles, with a progressive increase from the 1st to the 3rd
      tertile. At meta-regression, higher mean SYNTAX score was associated with higher
      risk for the primary outcome in the PCI group (beta =0.02, P=0.05), whereas no
      association was found with female gender, mean age, or diabetes. Conclusions:
      CABG remains the therapy of choice for the treatment of unprotected LMD,
      especially for patients with a high SYNTAX score.

PMID- 30094210
TI  - Incomplete revascularization: what the surgeon needs to know.
AB  - For many years, the concept of "complete revascularization" (CR) was considered
      an absolute truth in coronary surgery with improved long-term survival and a
      lower rate of reintervention. This was derived from early publications which
      showed a survival benefit for patients undergoing coronary artery bypass grafting
      (CABG) who received CR. Many advances in the field of coronary revascularization
      have been made in the years that passed since those publications, including more
      frequent use of percutaneous coronary intervention (PCI) in patients with
      multivessel disease (MVD). This has led some to question the importance of CR and
      raise the option of "reasonable incomplete revascularization" (IR) for selected
      patients. The definition of CR is variable in the literature with the two most
      common definitions being an anatomical (revascularization of all coronary
      segments with stenosis and larger than a predefined size) and a functional
      definition (where revascularization is considered complete if all ischemic and
      viable territories are reperfused). No randomized control trials have been
      conducted to compare complete versus IR, and a significant proportion of data is
      based on post hoc analysis of data from randomized control trials and registries.
      Multiple studies have proven that CR is achieved more frequently with CABG then
      with PCI. A review of the available data from the past three to four decades
      shows a trend toward improved results with CR, regardless of the reperfusion
      strategy chosen. This should impact the heart team discussion when choosing a
      revascularization strategy and impact the surgical decision making while
      preforming CABG. IR can be part of a hybrid revascularization strategy or be
      reserved for rare cases where the cost of achieving CR much outweighs the
      benefit.

PMID- 30094211
TI  - SYNTAX II and SYNTAX III trials: what is the take home message for surgeons?
AB  - Percutaneous coronary intervention (PCI) has evolved greatly in the last 40 years
      since its introduction by Andreas Gruntzig in 1977. Since then, we've observed an
      evolution in balloons, the development of stents, changes in stent structure,
      development of drug eluting stents, improvements in strut design, thickness and
      even their polymeric coating. Most recently we saw the rise and "fall" of
      bioabsorbable scaffolds for PCI. Trials with the most diverse devices for PCI and
      diagnostic techniques have been conducted. Two of the most recent trials were
      reported in the last year and deserve special attention-SYNTAX II and SYNTAX III.
      These trials are completely different in design but present valuable information
      for doctors managing coronary artery disease (CAD). Both trials take into account
      contemporary technology for assessing and treating CAD. The first uses so-called
      "state-of-the-art" PCI and compares the outcomes of that approach with the
      outcomes of the PCI arm of the pivotal SYNTAX trial. SYNTAX III Revolution on the
      other hand does not focus on clinical endpoints: it is a blinded trial that does
      not randomize patients but randomizes doctors ("the heart team") to make a
      decision on the best treatment for complex CAD. This decision was based either on
      multi-slice CT with physiological assessment using FFRCT or on conventional
      angiography. In this review we bring the most important aspects of those trials
      and the key messages for surgeons together; also, what the surgeon may expect in
      the future after the publication of these interesting concepts.

PMID- 30094212
TI  - Off-pump coronary artery bypass surgery with bilateral internal thoracic
      arteries: the Leipzig experience.
AB  - Background: Contrasting results of recent randomized controlled trials (RCTs)
      comparing off-pump and on-pump coronary artery bypass graft (CABG) surgery, as
      well as the lack of evidence for any survival benefit of bilateral internal
      thoracic artery (ITA) grafting over single ITA use, has intensified the debate
      about the role of the off-pump technique and bilateral ITA use in CABG surgery.
      We therefore investigated our 15-year experience in off-pump CABG with bilateral
      ITA grafting and evaluated temporal trends in preoperative characteristics and
      postoperative outcomes. Methods: Demographic, intra-operative, and outcome data
      of 1,199 consecutive patients undergoing off-pump CABG with bilateral ITA
      grafting was prospectively collected in a computerized database. Patients who
      underwent on-pump cardiac procedures and other extra-cardiac procedures were
      excluded from this study. Assessment of changes in perioperative characteristics
      and parameters with time was performed by dividing the whole cohort into three
      groups (2003-2007, 2008-2012, and 2013-2017) based on the year of surgery.
      Results: The overall 30-day mortality was 0.6%, with no differences observed
      between the three time cohorts (0.6%, 0.7%, 0.5%; P=0.8). The perioperative
      stroke rate for whole cohort was 0.6% and demonstrated a significant reduction in
      the last two time cohorts (1%, 0.5%, 0.5%; P<0.0001). The overall incidence of
      deep sternal wound infections was 0.7%, but was marginally higher in the last
      time-cohort (0.6%, 0.5%, 0.9%; P=0.7). Overall survival for the entire cohort was
      92.9%+/-1% and 78.9%+/-4% at 5 and 10 years follow-up, respectively. Older age at
      surgery and presence of peripheral vascular disease were the only predictors of
      late mortality. Conclusions: Off-pump CABG with bilateral skeletonized ITAs is a
      safe operation and is associated with a low mortality and morbidity, which can be
      maintained in high volume center unit over a long period of time. The long-term
      survival of patients undergoing such an operation is excellent.

PMID- 30094213
TI  - The radial artery is protective in women and men following coronary artery bypass
      grafting-a substudy of the radial artery patency study.
AB  - Background: Studies have demonstrated that female sex is an adverse risk factor
      in CABG. The primary aim of this study was to determine whether the radial artery
      (RA) was associated with reduced angiographic occlusion compared to the saphenous
      vein graft (SVG) stratified by sex in the multi-centered Radial Artery Patency
      Study (NCT00187356). Methods: Between 1996-2001, 529 patients less than 80 years,
      with graftable triple-vessel disease underwent isolated CABG across 11 centers
      with late angiographic and clinical follow-up. The primary objective was to
      compare complete occlusion of RA and SVG with respect to sex. The secondary
      objective was to determine cumulative patency of both grafts along with
      predictors of late graft occlusion stratified by sex. The additional objective
      was to compare major adverse cardiac events (MACE, defined as cardiac mortality,
      myocardial infarction or re-intervention) between women and men. Results: Of the
      529 enrolled patients (13.4% women), 269 (women: n=41, 15.2%) underwent late
      angiography at a mean of 7.7+/-1.5 years after CABG. Women were older (64.1+/-6.7
      versus 59.1+/-8.0 years, P<0.01) with a higher rate of diabetes (43.9% versus
      28.5%, P=0.05). Smoking history was less common (48.8% versus 75.4%, P<0.01)
      while the mean number of grafts per patient were similar (women: 3.8+/-0.7, men:
      3.8+/-0.6, P=0.65). RA occlusions were lower than SVG in women (RA: 9.8%, SVG:
      26.8%, P=0.05) and in men (RA: 8.8%, SVG: 17.1%, P=0.01). The rate of RA and SVG
      occlusion was not statistically different between women and men, and cumulative
      patency curves were also similar between sexes for the RA and study SVG.
      Multivariable modeling showed that having a RA (versus SVG) was protective in
      women [odds ratio (OR) 0.15, P=0.04] and men: (OR 0.49, P=0.02). MACE (P=0.15)
      and event-free cardiac survival (log-rank P=0.14) were similar between women and
      men. Conclusions: Radial arteries are protective in both women and men with
      comparable burden of coronary disease and revascularization.

PMID- 30094214
TI  - Hybrid coronary revascularization for the treatment of multivessel coronary
      artery disease.
AB  - Coronary artery disease (CAD) has typically been treated either medically, with
      percutaneous coronary intervention (PCI), or with coronary artery bypass grafting
      (CABG). As advances in stent technology and minimally invasive surgery have
      developed, a third option has emerged: hybrid coronary revascularization (HCR).
      In HCR, minimally invasive CABG and PCI are both employed to treat a single
      patient, often during the same hospital stay. Patients appropriate for this
      technique vary widely, from low-risk patients with low SYNTAX lesions outside the
      left anterior descending artery (LAD), to high-risk patients with multiple
      comorbidities who are felt by the heart team to benefit most by avoiding a
      sternotomy. Across both our experience and other series in the literature,
      mortality with HCR is around 1%. Hospital length of stay is less than one week,
      and typically less than after conventional CABG, but longer than with isolated
      PCI. Return to baseline activity is substantially shorter after minimally
      invasive CABG compared to conventional CABG due to the avoidance of a sternotomy;
      deep sternal wound infections are entirely avoided. Mid-term need for repeat
      revascularization may be higher with HCR, though randomized data are lacking. In
      conclusion, HCR is an evolving method to treat multivessel CAD with favorable
      early results in high volume centers, though growth in the field is limited by
      surgical experience and success with minimally invasive techniques.

PMID- 30094215
TI  - Coronary artery bypass grafting (CABG) vs. percutaneous coronary intervention
      (PCI) in the treatment of multivessel coronary disease: quo vadis? -a review of
      the evidences on coronary artery disease.
AB  - The optimal treatment of ischemic coronary artery disease (CAD) is still
      controversial. A number of randomized controlled trials (RCT) and several meta
      analyses have been performed and are inspiring the current guidelines. However, a
      univocal consensus on the optimal therapeutic strategy for multivessel disease
      has still not been reached yet. We reviewed the current evidence on this topic,
      focusing on both RCT and meta-analyses. From both short and long-term studies, it
      emerges that in patients with multivessel disease, coronary artery bypass
      grafting (CABG) is associated with better survival, lower rates of major
      cardiovascular events (specifically myocardial infarction or stroke) and repeat
      revascularization as compared with percutaneous coronary intervention (PCI) with
      drug-eluting stents.

PMID- 30094216
TI  - Coronary artery bypass grafting-fifty years of quality initiatives since
      Favaloro.
AB  - Coronary artery bypass grafting (CABG) remains one of the most commonly performed
      major surgical procedures worldwide and the most common procedure performed by
      cardiac surgeons. Rene Favaloro is widely credited with recognizing the true
      potential of CABG and subsequently popularizing the technique in a broad manner.
      Since the era of Favaloro in the late 1960s, the evolution of CABG can be
      understood through a series of quality initiatives that have defined which
      patients can benefit from the procedure and via which technique(s) they will
      derive the greatest benefit. Herein, we will review some of the key developments
      in CABG over the last 50 years with a focus on ongoing quality initiatives that
      will continue to refine the optimal applications and outcomes of CABG for the
      next 50 years.

PMID- 30094217
TI  - Percutaneous coronary intervention in left main disease: SYNTAX, PRECOMBAT, EXCEL
      and NOBLE-combined cardiology and cardiac surgery perspective.
AB  - Although coronary-artery bypass grafting (CABG) is the standard choice of
      revascularization for significant left main coronary artery (LMCA) disease,
      percutaneous coronary intervention (PCI) for LMCA disease has been widely
      expanded with adoption of drug-eluting stents (DES). Several small- and moderate
      sized trials of CABG and first-generation DES showed that PCI might be a good
      alternative for selected patients with LMCA disease. However, these early trials
      were relatively underpowered and comparative results of contemporary DES and CABG
      were clearly required. Subsequently, two large-sized trials comparing CABG and
      contemporary DES (EXCEL and NOBLE) were conducted, but these trials showed
      conflicting results with regards to the effects of PCI and CABG on clinical
      outcomes, which raises further uncertainty on the optimal revascularization for
      LMCA disease. This article serves to summarize the key findings of landmark
      clinical trials, to share our knowledge and experience and to express personal
      opinions on current controversies in the treatment of LMCA disease.

PMID- 30094218
TI  - Pivotal contemporary trials of percutaneous coronary intervention vs. coronary
      artery bypass grafting: a surgical perspective.
AB  - Coronary artery bypass grafting (CABG) and percutaneous coronary intervention
      (PCI) are the two revascularization strategies for patients with coronary artery
      disease (CAD). While CABG continues to be the gold standard for
      revascularization, advancements in PCI technology have triggered numerous, often
      industry-funded investigations to challenge this role. This perspective will
      provide a summary of previous RCTs comparing CABG vs. PCI. The recently published
      NOBLE and EXCEL trials will be discussed in depth. Future directions of research
      pertaining to CABG vs. PCI will be briefly discussed in this document.

PMID- 30094219
TI  - What the surgeon needs to know about percutaneous coronary intervention treatment
      of chronic total occlusions.
AB  - Chronic total occlusion (CTO) accounts for 10-20% of lesions identified in
      coronary artery disease (CAD) patients. CTO percutaneous coronary intervention
      (PCI) is one of the most challenging of lesion subsets due to its technical
      difficulty, requiring specific operator expertise and equipment. There has been
      increased interest on CTO PCI evolving with the development of novel techniques
      and dedicated devices. Furthermore, in order to effectively and systematically
      utilize these techniques and devices, CTO PCI algorithms have been established.
      All of these developments have resulted in procedural success rates increasing to
      approximately 90%. In this review, we outline the evidence base for CTO PCI,
      conventional and contemporary CTO PCI techniques, CTO algorithms and outline
      integrated management strategies between cardiac surgeons and interventional
      cardiologists.

PMID- 30094220
TI  - Is there a role for fractional flow reserve in coronary artery bypass graft
      (CABG) planning?
AB  - The concept of significant lesions has substantially evolved over the last
      decade. With growing evidence for use of fractional flow reserve (FFR) as a
      determinant of lesion-specific ischemia and its superiority to angiography-guided
      revascularization and medical therapy, the field of percutaneous
      revascularization has shifted to rely exclusively on FFR instead of luminal
      stenosis alone in guiding revascularization. This transition to physiological
      assessment has not yet made it to the realm of surgical revascularization. FFR
      guided therapy has been shown to be superior to angiography-guided therapy mainly
      by safe deferral of about 1/3rd of lesions, leading to less periprocedural events
      and better outcomes. Is it possible that utilization of FFR-guided CABG would
      lead to less complicated procedures, shorter operating times, more frequent off
      pump CABG procedures and more hybrid procedures? Can FFR-guided CABG improve the
      cardiovascular outcomes as compared to current standard of practice? In the
      following paragraphs we review the concept of FFR, the evidence behind FFR-guided
      therapy, the emerging data regarding use FFR-guided CABG and discuss where the
      revascularization field is headed.

PMID- 30094222
TI  - On-pump total arterial revascularization.

PMID- 30094223
TI  - Multiple arterial, minimally invasive coronary surgery (MA-MICS).

PMID- 30094221
TI  - Dual inflow, total-arterial, anaortic, off-pump coronary artery bypass grafting:
      how to do it.
AB  - Coronary surgery performed on an arrested heart, using one internal mammary
      artery and a saphenous vein carries two main potential drawbacks: the known
      failure rate of vein grafts and the relatively high rate of neurologic injury. To
      address these concerns, we describe a technique that achieves complete
      revascularization without manipulating the ascending aorta (anaortic, off-pump)
      and utilizing total arterial grafts. All patients undergo thorough preoperative
      investigation, including bilateral carotid, vertebral and subclavian artery
      Duplex ultrasounds. A pulmonary artery catheter, transoesophageal
      echocardiography, and point-of-care coagulation testing are used in each case.
      The left and right internal mammary arteries and non-dominant radial artery are
      harvested using a fully skeletonised technique. Wide bilateral extrapleural
      retrothymic tunnels are developed and the pericardium is opened widely to
      facilitate cardiac positioning. A tandem graft is constructed with the right
      internal mammary artery (RIMA) in situ and radial artery using an end-to-end
      anastomosis. This graft is brought into the pericardium and through the
      transverse sinus in order to graft the lateral and inferior walls with multiple
      sequential distal anastomoses. The left internal mammary artery (LIMA) in situ is
      used to graft the anterior wall. Four main cardiac positions (high and low
      lateral walls, inferior and anterior walls) are obtained using a combination of
      off-pump stabilizer positioning, alternate tension on pericardial 'heart
      strings', table tilting and folded wet sponges. All distal anastomoses are
      performed using silastic intracoronary shunts and an off-pump myocardial
      stabilizer. All grafts are checked using transit-flow time measurements.
      Milrinone is continued overnight and dual antiplatelet therapy is continued for 3
      months postoperatively.

PMID- 30094224
TI  - The Prevention of Brain Metastases in Non-Small Cell Lung Cancer by Prophylactic
      Cranial Irradiation.
AB  - Background: Non-small cell lung cancer (NSCLC) patients frequently develop brain
      metastases (BM), even though the initial imaging with brain CT or MRI was
      negative. Stage III patients have the highest risk to develop BM, with an
      incidence of approximately 30%. BM can lead to neurocognitive disorders, loss of
      quality of life (QoL), and they are the most important factors influencing
      patient's overall survival (OS). Although a radical local treatment of BM may be
      possible with primary radiosurgery or after resection, the prognosis often
      remains poor. Preventing the development of BM through prophylactic cranial
      irradiation (PCI) may improve the outcome of these patients. Methods: Data from
      published randomized trials comparing PCI with non-PCI were sought using
      electronic database (PubMed) searching, hand searching, and by contacting
      experts. Trials were included if they considered a randomized comparison of PCI
      and non-PCI, enrolled NSCLC patients, excluded patients with recurrent or
      metastatic disease, and reported results on BM occurrence. Each randomized
      controlled trial (RCT) was assessed for methodological quality using the Cochrane
      collaboration's tool for the assessment of risk of bias. Study estimates were
      pooled using a fixed effects sample-weighted meta-analysis approach to calculate
      an overall estimate and 95% confidence interval (CI). Results on PCI-related
      toxicity, QoL, and OS were only reported descriptively. Results: Seven RCTs were
      included in the meta-analysis. In total, 1,462 patients were analyzed, including
      717 patients who received PCI and 745 patients who did not. The risk of
      developing BM was significantly decreased through PCI (13% reduction, RR 0.33;
      95% CI 0.22-0.45). PCI-related toxicity and QoL data were limited. Acute toxicity
      mostly included fatigue, skin-related toxicity, and nausea or vomiting. Late
      toxicities such as headache, dyspnea, lethargy, and low grade cognitive
      impairments were also reported in some of the included RCTs. Results on OS were
      inconclusive. Conclusion: The risk of developing BM was reduced in patients who
      received PCI compared to patients who did not. To implement PCI as the standard
      treatment for patients with NSCLC, the impact of PCI-related toxicity on QoL
      should be further investigated, as well as long-term OS. A future individual
      patient data meta-analysis could produce definitive answers to this clinical
      question.

PMID- 30094225
TI  - The Human Centrosomal Protein CCDC146 Binds Chlamydia trachomatis Inclusion
      Membrane Protein CT288 and Is Recruited to the Periphery of the Chlamydia
      Containing Vacuole.
AB  - Chlamydia trachomatis is an obligate intracellular human pathogen causing mainly
      ocular and genital infections of significant clinical and public health impact.
      C. trachomatis multiplies intracellularly in a membrane bound vacuole, known as
      inclusion. Both extracellularly and from within the inclusion, C. trachomatis
      uses a type III secretion system to deliver several effector proteins into the
      cytoplasm of host cells. A large proportion of these effectors, the inclusion
      membrane (Inc) proteins, are exposed to the host cell cytosol but possess a
      characteristic hydrophobic domain mediating their insertion in the inclusion
      membrane. By yeast two-hybrid, we found that C. trachomatis Inc CT288 interacts
      with the human centrosomal protein CCDC146 (coiled-coil domain-containing protein
      146). The interaction was also detected by co-immunoprecipitation in mammalian
      cells either ectopically expressing CCDC146 and CT288 or ectopically expressing
      CCDC146 and infected by a C. trachomatis strain expressing epitope-tagged and
      inclusion membrane-localized CT288. In uninfected mammalian cells, ectopically
      expressed full-length CCDC146 (955 amino acid residues) localized at the
      centrosome; but in cells infected by wild-type C. trachomatis, its centrosomal
      localization was less evident and CCDC146 accumulated around the inclusion.
      Recruitment of CCDC146 to the inclusion periphery did not require intact host
      Golgi, microtubules or microfilaments, but was dependent on chlamydial protein
      synthesis. Full-length CCDC146 also accumulated at the periphery of the inclusion
      in cells infected by a C. trachomatis ct288 mutant; however, a C-terminal
      fragment of CCDC146 (residues 692-955), which interacts with CT288, showed
      differences in localization at the periphery of the inclusion in cells infected
      by wild-type or ct288 mutant C. trachomatis. This suggests a model in which
      chlamydial proteins other than CT288 recruit CCDC146 to the periphery of the
      inclusion, where the CT288-CCDC146 interaction might contribute to modulate the
      function of this host protein.

PMID- 30094226
TI  - Artemisinin Derivatives and Synthetic Trioxane Trigger Apoptotic Cell Death in
      Asexual Stages of Plasmodium.
AB  - Although over the last 15 years, prevalence of malaria became reduced by over
      half but developing resistance against artemisinin derivatives and its
      combinations, which are only ray of hope to treat resistant malaria set back the
      control efforts and the key hinderence to achieve the goal of malaria elimination
      till 2030. In spite these artemisinins are precious antimalarials, their action
      mechanism is yet to be fully understood. Reactive oxygen species (ROS) produces
      by cleavage of endoperoxide bridge of artemisinin derivatives are known to be its
      antimalarial efficacy. Since ROS could induce apoptosis, here we had explored the
      effect of artemisinin derivatives on apoptotic machinery of malaria parasite,
      Plasmodium falciparum and its survival. We have studied the effect of a/beta
      arteether, artesunate and a synthetic 1, 2, 4 trioxane on mitochondria, caspase
      activity and DNA during asexual blood stages of Plasmodium falciparum 3D7.
      Results have shown that cleavage of peroxide bridge of artemisinin derivatives
      and 1,2,4 trioxane generate reactive oxygen species which depolarize
      mitochondrial membrane potential and make it permeable which further followed by
      activation of caspase like enzyme and DNA fragmentation, which are hallmark of
      apoptotic cell death. These findings suggest that artemisinin derivatives and
      synthetic trioxane induce apoptosis like phenomena in erythrocytic stage of
      malaria parasite; Plasmodium falciparum.

PMID- 30094227
TI  - Anatomical study of the location of the antilingula, lingula, and mandibular
      foramen for vertical ramus osteotomy.
AB  - Background: The purpose of this study was to identify the location of the
      antilingula, lingula, and mandibular foramen in Korean cadavers and to promote
      safe and accurate surgery without damage to the inferior alveolar neurovascular
      bundle (IANB) when performing a vertical ramus osteotomy (VRO). Methods: This
      study was conducted on the dried mandibles of 20 adult cadavers. Digital calipers
      were used to measure the distances from the anatomical reference points
      (antilingula, lingula, and mandibular foramen). Result: The antilingula was
      located at the anterior 44% and superior 31% in the ramus. The lingula was
      located at the anterior 55% and superior 30% in the ramus. The mandibular foramen
      was located at the anterior 58% and superior 46% in the ramus. Regarding the
      positional relationship with the antilingula, the lingula was located 0.54 mm
      superior and 4.19 mm posterior, and the mandibular foramen was located 6.95 mm
      inferior and 4.98 mm posterior. The results suggested that in order to prevent
      damage to the IANB, osteotomy should be performed in the posterior region of
      ramus at least 29% of the total horizontal length of the ramus. Conclusion: Using
      only the antilingula as a reference point is not guaranteed to IANB injury.
      However, it is still important as a helpful reference point for the surgeon in
      the surgical field.

PMID- 30094228
TI  - The Incidence of Road Traffic Crashes Among Young People Aged 15-20 Years:
      Differences in Behavior, Lifestyle and Sociodemographic Indices in the Galilee
      and the Golan.
AB  - Background: Adolescent injuries and fatalities constitute a world health concern
      and present a major public health burden. Of all childhood injuries in Israel
      61.8% occur during road traffic crashes. The risk of being injured or killed in a
      road traffic crash is especially high among individuals deemed to have a low
      socio-economic status, but, there also exist crucial risk factors for road
      traffic crashes that are intrinsic social determinants of health, including
      behavior, lifestyle, education and employment. These associations are explored in
      this study. Aim: To examine the contribution of socioeconomic inequalities to the
      incidence of road traffic crashes among adolescents living in the Galilee and the
      Golan. Methods: A large retrospective study of trauma records (N = 3293) of 15-20
      year-old patients who were injured in road traffic crashes and admitted to Ziv
      Medical Center between 2004 and 2015 was performed. These patients were
      subcategorized according to their home address. Using census data and other
      databases associations between socioeconomic inequalities, intrinsic social
      determinants and the prevalence of road crashes were investigated. Results: Road
      traffic crashes in the Galilee and the Golan are more frequent among residents of
      low socioeconomic areas. Fifty-five percent of drivers are from the areas of
      lowest socioeconomic level (levels 2 to 4) and are responsible for 60% of the
      road traffic injuries admitted to Ziv Medical Center (p < 0.001). In contrast,
      42% of drivers are from areas of medium socioeconomic level (levels 5 and 6) but
      are responsible for only 35% of road traffic injuries (p < 0.001). Young women in
      the Galilee and the Golan are less likely to be involved in road traffic crashes
      35.8% compared to 64.2% in young men. Conclusions: This research has shown that
      youth, male gender, socioeconomic status, education level and the quality of road
      infrastructure are important factors in the incidence of road traffic crashes in
      the Galilee and the Golan. This should be taken into consideration by policy
      makers in order to develop appropriate interventions in road safety targeted at
      multiple levels.

PMID- 30094229
TI  - Metamizole Utilization and Expenditure During 6-Year Period: Serbia vs. Croatia.
AB  - Background: Metamizole is a medication with analgesic, antipyretic, spasmolytic,
      and weak anti-inflammatory effects. The aim of our study was to evaluate a six
      year trend in the utilization and expenditure of metamizole in comparison to
      other group of licensed non-opioid analgesics in Serbia and Croatia, in order to
      rationalize its use and prescribing in these countries. Methods: The data of
      metamizole vs. all other non-opioid analgesics utilization and expenditure in
      Serbia and Croatia was analyzed according to the WHO methodology and expressed as
      defined daily doses per 1,000 inhabitants per day (DDD/1,000 inhabitants/per day)
      and total costs, respectively, during the 6-year period from 2010 to 2015.
      Results: In the observed period, utilization of metamizole was 3.31 fold higher
      in Serbia than in Croatia (median in Serbia was 2.238 vs. 0.675 in Croatia
      DDD/1,000 inhabitants/per day/per year). Expenditure of metamizole in the same
      period was 5.29-fold higher in Serbia than in Croatia (median in Serbia was
      1,738,192.51 ?/per year vs. 328,355.03 ?/per year in Croatia). Conclusion:
      Utilization and expenditure of non-opioid analgesics, including metamizole, in
      Serbia was significantly higher comparing with Croatia.Further research is needed
      to determine whether the current analgesic consumption in Serbia meets the needs
      of the patient. The benefits of metamizole should be weighed against the risk of
      metamizole-induced adverse effects. Until then, its prescribing should be based
      on indications and the appropriate duration of therapy.

PMID- 30094230
TI  - Tuning the Catalytic Activity of Ir@Pt Nanoparticles Through Controlling Ir Core
      Size on Cathode Performance for PEM Fuel Cell Application.
AB  - Pulse electrochemically synthesis of a series of core-shell structured Ir@Pt/C
      catalysts in cathode catalysts layer are achieved to fabricate membrane electrode
      assemblies (MEA) with cathode ultra-low Pt loading. The single cell performance
      of the MEAs in a H2/air PEMFC greatly rely on the sizes of the Ir core
      nanoparticle, and the optimum activity occurs with Ir core size of 4.1 nm. The
      cathode MEA with core-shell structured catalysts with optimal Ir core size
      exhibited excellent performance in a H2/air single fuel cell, comparable to that
      of a commercial Pt/C MEA (Johnson Matthey 40% Pt), even though the Pt loading in
      Ir@Pt was only 40% that of the commercial Pt cathode (0.04 vs. 0.1 mg cm-2). The
      catalysts were characterized by X-ray diffraction, X-ray photoelectron
      spectroscopy (XPS) and scanning transmission electron microscopy. Based on the
      characterization results, especially from XPS, we suggest that the effect of Ir
      core particle size on MEA performance may arise from the interactions between the
      Pt shell and the Ir core. The XPS results showed that the Ir@Pt/C-300 catalyst
      has the highest Pt0 fraction among the four tested samples. This work
      demonstrates the alternative to enhance the cathode performance in single cell of
      Pt-based core-shell structured catalysts by varying size of the core metal under
      the Pt shell.

PMID- 30094231
TI  - Efficient Non-fullerene Organic Solar Cells Enabled by Sequential Fluorination of
      Small-Molecule Electron Acceptors.
AB  - Three small-molecule non-fullerene electron acceptors containing different
      numbers of fluorine atoms in their end groups were designed and synthesized. All
      three acceptors were found to exhibit relatively narrow band gaps with absorption
      profiles extending into the near-infrared region. The fluorinated analog
      exhibited enhanced light-harvesting capabilities, which led to improved short
      circuit current densities. Moreover, fluorination improved the blend film
      morphology and led to desirable phase separation that facilitated exciton
      dissociation and charge transport. As a result of these advantages, organic solar
      cells based on the non-fullerene acceptors exhibited clearly improved short
      circuit current densities and power conversion efficiencies compared with the
      device based on the non-fluorinated acceptor. These results suggest that
      fluorination can be an effective approach for the molecular design of non
      fullerene acceptors with near-infrared absorption for organic solar cells.

PMID- 30094232
TI  - The Metabolome of a Cyanobacterial Bloom Visualized by MS/MS-Based Molecular
      Networking Reveals New Neurotoxic Smenamide Analogs (C, D, and E).
AB  - Members of the cyanobacterial genus Trichodesmium are well known for their
      substantial impact on nitrogen influx in ocean ecosystems and the enormous
      surface blooms they form in tropical and subtropical locations. However, the
      secondary metabolite composition of these complex environmental bloom events is
      not well known, nor the possibility of the production of potent toxins that have
      been observed in other bloom-forming marine and freshwater cyanobacteria species.
      In the present work, we aimed to characterize the metabolome of a Trichodesmium
      bloom utilizing MS/MS-based molecular networking. Furthermore, we integrated
      cytotoxicity assays in order to identify and ultimately isolate potential
      cyanotoxins from the bloom. These efforts led to the isolation and identification
      of several members of the smenamide family, including three new smenamide analogs
      (1-3) as well as the previously reported smenothiazole A-hybrid polyketide
      peptide compounds. Two of these new smenamides possessed cytotoxicity to neuro-2A
      cells (1 and 3) and their presence elicits further questions as to their
      potential ecological roles. HPLC profiling and molecular networking of
      chromatography fractions from the bloom revealed an elaborate secondary
      metabolome, generating hypotheses with respect to the environmental role of these
      metabolites and the consistency of this chemical composition across genera, space
      and time.

PMID- 30094233
TI  - Structural and Biochemical Properties of Duckweed Surface Cuticle.
AB  - The plant cuticle, which consists of cutin and waxes, forms a hydrophobic coating
      covering the aerial surfaces of all plants. It acts as an interface between
      plants and their surrounding environment whilst also protecting them against
      biotic and abiotic stresses. In this research, we have investigated the
      biodiversity and cuticle properties of aquatic plant duckweed, using samples
      isolated from four different locations around Hongze lake in Jiangsu province,
      China. The samples were genotyped using two chloroplast markers and nuclear
      ribosomal DNA markers, which revealed them as ecotypes of the larger duckweed,
      Spirodela polyrhiza. Duckweed cuticle properties were investigated by
      compositional analysis using Gas Chromatography coupled with Mass Spectroscopy
      (GC-MS) Flame Ionization Detector (GC-FID), and ultrastructural observation by
      cryo-Scanning Electron Microscopy (cryo-SEM). Cuticle compositional analysis
      indicated that fatty acids and primary alcohols, the two typical constituents
      found in many land plant cuticle, are the major duckweed wax components. A large
      portion of the duckweed wax fraction is composed of phytosterols, represented by
      campesterol, stigmasterol, sitosterol and their common precursor squalene. The
      cryo-SEM observation uncovered significant differences between the surface
      structures of the top air-facing and bottom water-facing sides of the plant
      fronds. The top side of the fronds, containing multiple stomata complexes,
      appeared to be represented by a rather flat waxy film sporadically covered with
      wax crystals. Underneath the waxy film was detected a barely distinguished
      nanoridge net, which became distinctly noticeable after chloroform treatment. On
      the bottom side of the fronds, the large epidermal cells were covered by the well
      structured net, whose sections became narrower and sharper under cryo-SEM
      following chloroform treatment. These structural differences between the abaxial
      and adaxial sides of the fronds evidently relate to their distinct physiological
      roles in interacting with the contrasting environments of sunlight/air and
      nutrients/water. The unique structural and biochemical features of Spirodela
      frond surfaces with their rapid reproductive cycle and readily availability
      genome sequence, make duckweed an attractive monocot model for studying the
      fundamental processes related to plant protection against ultraviolet
      irradiation, pathogens and other environmental stresses.

PMID- 30094234
TI  - Comparison of 2-Aminobenzamide, Procainamide and RapiFluor-MS as Derivatizing
      Agents for High-Throughput HILIC-UPLC-FLR-MS N-glycan Analysis.
AB  - Rising awareness of the universal importance of protein N-glycosylation governs
      the development of further advances in N-glycan analysis. Nowadays it is well
      known that correct glycosylation is essential for proper protein function, which
      emanates from its important role in many physiological processes. Furthermore,
      glycosylation is involved in pathophysiology of multiple common complex diseases.
      In the vast majority of cases, N-glycosylation profiles are analyzed from
      enzymatically released glycans, which can be further derivatized in order to
      enhance the sensitivity of the analysis. Techniques wherein derivatized N-glycans
      are profiled using hydrophilic interaction chromatography (HILIC) with
      fluorescence (FLR) and mass spectrometry (MS) detection are now routinely
      performed in a high-throughput manner. Therefore, we aimed to examine the
      performance of frequently used labeling compounds -2-aminiobenzamide (2-AB) and
      procainamide (ProA), and the recently introduced RapiFluor-MS (RF-MS) fluorescent
      tag. In all experiments N-glycans were released by PNGase F, fluorescently
      derivatized, purified by HILIC solid phase extraction and profiled using HILIC
      UPLC-FLR-MS. We assessed sensitivity, linear range, limit of quantification
      (LOQ), repeatability and labeling efficiency for all three labels. For this
      purpose, we employed in-house prepared IgG and a commercially available IgG as a
      model glycoprotein. All samples were analyzed in triplicates using different
      amounts of starting material. We also tested the performance of all three labels
      in a high-throughput setting on 68 different IgG samples, all in duplicates and
      22 identical IgG standards. In general, ProA labeled glycans had the highest FLR
      sensitivity (15-fold and 4-fold higher signal intensities compared to 2-AB and RF
      MS respectively) and RF-MS had the highest MS sensitivity (68-fold and 2-fold
      higher signal intensities compared to 2-AB and ProA, respectively). ProA and RF
      MS showed comparable limits of quantification with both FLR and MS detection,
      whilst 2-AB exhibited the lowest sensitivity. All labeling procedures showed good
      and comparable repeatability. Furthermore, the results indicated that labeling
      efficiency was very similar for all three labels. In conclusion, all three labels
      are a good choice for N-glycan derivatization in high-throughput HILIC-UPLC-FLR
      MS N-glycan analysis, although ProA and RF-MS are a better option when higher
      sensitivity is needed.

PMID- 30094236
TI  - Surgical Approaches and Their Outcomes in the Treatment of Cubital Tunnel
      Syndrome.
AB  - Purpose: This review was undertaken in order to provide an updated summary of the
      current literature on outcomes for various surgical treatments for cubital tunnel
      syndrome. Methods: Studies reporting outcomes for surgical treatment of cubital
      tunnel syndrome were collected through the PubMed database. Study structure,
      number of participants/procedures, mean follow-up times, scoring scales, and
      outcomes were collected according to the type of surgery: open decompression,
      endoscopic decompression, minimal incision, subcutaneous transposition,
      intramuscular transposition, and submuscular transposition. Results: Our findings
      indicate varying but comparable levels of success among all surgical techniques
      reviewed. Many different scoring scales were utilized, limiting direct
      quantitative comparison between most studies. Discussion: While some studies
      directly compared two or more techniques, there was rarely a statistically
      significant difference between groups. In comparisons that did reach
      statistically significant differences, there were others yet that found no
      difference in comparing the same techniques. Conclusions: None of the techniques
      in this review has demonstrated universal superiority above all others, but all
      appear to be effective in the treatment of cubital tunnel syndrome. The only
      consensus seems to be that transposition is preferred where the ulnar nerve tends
      to subluxate either on preoperative or intraoperative examination.

PMID- 30094235
TI  - Skin Tissue Substitutes and Biomaterial Risk Assessment and Testing.
AB  - Tremendous progress has been made over the past few decades to develop skin
      substitutes for the management of acute and chronic wounds. With the advent of
      tissue engineering and the ability to combine advanced manufacturing technologies
      with biomaterials and cell culture systems, more biomimetic tissue constructs
      have been emerged. Synthetic and natural biomaterials are the main constituents
      of these skin-like constructs, which play a significant role in tissue grafting,
      the body's immune response, and the healing process. The act of implanting
      biomaterials into the human body is subject to the body's immune response, and
      the complex nature of the immune system involves many different cell types and
      biological processes that will ultimately determine the success of a skin graft.
      As such, a large body of recent studies has been focused on the evaluation of the
      performance and risk assessment of these substitutes. This review summarizes the
      past and present advances in in vitro, in vivo and clinical applications of
      tissue-engineered skins. We discuss the role of immunomodulatory biomaterials and
      biomaterials risk assessment in skin tissue engineering. We will finally offer a
      roadmap for regulating tissue engineered skin substitutes.

PMID- 30094237
TI  - Insect Arylalkylamine N-Acyltransferases: Mechanism and Role in Fatty Acid Amide
      Biosynthesis.
AB  - Arylalkylamine N-acyltransferases (AANATs) catalyze the formation of an N
      acylamide from an acyl-CoA thioester and an amine. One well known example is the
      production of N-acetylserotonin from acetyl-CoA and serotonin, a reaction in the
      melatonin biosynthetic pathway from tryptophan. AANATs have been identified from
      a variety of vertebrates and invertebrates. Considerable efforts have been
      devoted to the mammalian AANAT because a cell-permeable inhibitor specifically
      targeted against this enzyme could prove useful to treat diseases related to
      dysfunction in melatonin production. Insects are an interesting model for the
      study of AANATs because more than one isoform is typically expressed by a
      specific insect and the different insect AANATs (iAANATs) serve different roles
      in the insect cell. In contrast, mammals express only one AANAT. The major role
      of iAANATs seem to be in the production of N-acetyldopamine, a reaction important
      in the tanning and sclerotization of the cuticle. Metabolites identified in
      insects including N-acetylserotonin and long-chain N-fatty acyl derivatives of
      dopamine, histidine, phenylalanine, serotonin, tyrosine, and tryptophan are
      likely produced by an iAANAT. In vitro studies of specific iAANATs are consistent
      with this hypothesis. In this review, we highlight the current metabolomic
      knowledge of the N-acylated aromatic amino acids and N-acylated derivatives of
      the aromatic amino acids, the current mechanistic understanding of the iAANATs,
      and explore the possibility that iAANATs serve as insect "rhymezymes" regulating
      photoperiodism and other rhythmic processes in insects.

PMID- 30094238
TI  - Precision Medicine for Neonatal Sepsis.
AB  - Neonatal sepsis remains a significant cause of morbidity and mortality especially
      in the preterm infant population. The ability to promptly and accurately diagnose
      neonatal sepsis based on clinical evaluation and laboratory blood tests remains
      challenging. Advances in high-throughput molecular technologies have increased
      investigations into the utility of transcriptomic, proteomic and metabolomic
      approaches as diagnostic tools for neonatal sepsis. A systems-level understanding
      of neonatal sepsis, obtained by using omics-based technologies (at the
      transcriptome, proteome or metabolome level), may lead to new diagnostic tools
      for neonatal sepsis. In particular, recent omic-based studies have identified
      distinct transcriptional signatures and metabolic or proteomic biomarkers
      associated with sepsis. Despite the emerging need for a systems biology approach,
      future studies have to address the challenges of integrating multi-omic data with
      laboratory and clinical meta-data in order to translate outcomes into precision
      medicine for neonatal sepsis. Omics-based analytical approaches may advance
      diagnostic tools for neonatal sepsis. More research is needed to validate the
      recent systems biology findings in order to integrate multi-dimensional data
      (clinical, laboratory and multi-omic) for future translation into precision
      medicine for neonatal sepsis. This review will discuss the possible applications
      of omics-based analyses for identification of new biomarkers and diagnostic
      signatures for neonatal sepsis, focusing on the immune-compromised preterm infant
      and considerations for clinical translation.

PMID- 30094240
TI  - Commentary: Decomposition of Heart Rate Variability Spectrum into a Power-Law
      Function and a Residual Spectrum.

PMID- 30094239
TI  - Structural Components for Amplification of Positive and Negative Strand VEEV
      Splitzicons.
AB  - RNA is a promising nucleic acid technology for both vaccines and therapeutics,
      and replicon RNA has gained traction as a next-generation RNA modality. Replicon
      RNA self-amplifies using a replicase complex derived from alphaviral non
      structural proteins and yields higher protein expression than a similar dose of
      messenger RNA. Here, we debut RNA splitzicons; a split replicon system wherein
      the non-structural proteins (NSPs) and the gene of interest are encoded on
      separate RNA molecules, but still exhibit the self-amplification properties of
      replicon RNA. We designed both positive and negative strand splitzicons encoding
      firefly luciferase as a reporter protein to determine which structural
      components, including the 5' untranslated region (UTR), a 51-nucleotide conserved
      sequence element (CSE) from the first nonstructural protein, the subgenomic
      promoter (SGP) and corresponding untranslated region, and an internal ribosomal
      entry site (IRES) affect amplification. When paired with a NSP construct derived
      from the whole, wild type replicon, both the positive and negative strand
      splitzicons were amplified. The combination of the 51nt CSE, subgenomic promoter
      and untranslated region were imperative for the positive strand splitzicon, while
      the negative strand was amplified simply with inclusion of the subgenomic
      promoter. The splitzicons were amplified by NSPs in multiple cell types and show
      increasing protein expression with increasing doses of NSP. Furthermore, both the
      positive and negative strand splitzicons continued to amplify over the course of
      72 h, up to >100,000-fold. This work demonstrates a system for screening the
      components required for amplification from the positive and negative strand
      intermediates of RNA replicons and presents a new approach to RNA replicon
      technology.

PMID- 30094241
TI  - Characteristics and Prognosis of Exercise-Related Sudden Cardiac Arrest.
AB  - Introduction: The previous studies about exercise-related sudden cardiac arrest
      (SCA) have mainly focused on sports activity, but information related to SCA in
      other forms of physical exercise is lacking. Our aim was to identify
      characteristics and prognosis of SCA victims in the general population who
      suffered SCA during physical activity. Methods and results: We collected
      retrospectively all cases of attempted resuscitation in Oulu University Hospital
      Area between 2007 and 2012. A total of 300 cases were of cardiac origin. We only
      included witnessed cases with Emergency Medical System arrival time <=15 min.
      Cases of low-intensity physical activity were excluded. A total of 47 SCAs
      occurred during moderate-to-vigorous physical activity (exercise-group) and 43
      cases took place at rest (rest-group). The subjects in exercise-group were
      younger compared to the rest-group (60 +/- 14 years vs. 67 +/- 14 years, p =
      0.016). The initial rhythm recorded was more often ventricular fibrillation (VF)
      in exercise-group compared to the rest-group (77 vs. 50%, p = 0.010). Pulseless
      electrical activity (PEA) was rare in exercise-group compared to the rest -group
      (2.1 vs. 14%, p = 0.033, respectively). Bystander cardiopulmonary resuscitation
      (CPR) was more often performed when SCA took place during physical exercise (47
      vs. 23 %, p = 0.020). Survival rates to hospital discharge were higher in the
      exercise-group compared to the rest -group (49 vs. 9.3%, p < 0.0001).
      Conclusions: SCA occurring during physical activity is more frequently a result
      of VF and bystander CPR is more often performed. There is also a notably better
      survival rate to hospital discharge.

PMID- 30094242
TI  - Repellent and Lethal Activities of Extracts From Fruits of Chinaberry (Melia
      azedarach L., Meliaceae) Against Triatoma infestans.
AB  - Triatoma infestans is the principal vector of Trypanosoma cruzi, parasite
      responsible of Chagas's Disease transmission in Argentina. Pyrethroids have
      become common pesticides for the control of T. infestans but increasing
      resistance encourages the search of new alternatives and the use of natural
      products for biological control arises as a new strategy. Melia azedarach L. is
      originated from the Himalaya's region and several compounds are part of its rich
      phytochemistry. Folk medicine of the plant is due to its repellent and
      insecticidal activities. Aims of this work were to evaluate the repellent
      activity of methanolic and acetonic extracts from fruits of M. azedarach by means
      of the area preference method of fifth and first nymph stages as well as to test
      the acute lethal effect of the more repellent extract by means of direct
      application on cuticle on both stages. For repellence, qualitative filter papers
      were divided into two halves, one treated with methanolic (ME) or acetonic (AC)
      extract and the other without treatment. Controls were impregnated half with
      methanol or acetone and half without the solvents. One nymph was located in each
      Petri or well and repellence percentage was determined. For the lethal effect,
      fasted and fed to repletion 5th stage nymphs were topically administered with
      different concentrations of AC and deaths were registered after 24, 48, 72, 96,
      and 120 h. Phytochemical analysis of extracts was performed as well. AC
      demonstrated high repellent activity (100%, both stages), whereas ME extract
      activity was slight (10-21%). AC extract was selected for lethal assays due to
      early repellent activity. Fed to repletion nymphs were more sensitive to the
      lethal activity of the extract when compared to fasted nymphs (LD50: 11.5 vs.
      23.1 MUg/insect, respectively). Phytochemistry assays of extracts showed a higher
      concentration of flavonoids, alkaloids and triterpenes for AC. Considering these
      results, next assays will include the test of Melia azedarach extract on T.
      infestans that are resistant to pyrethroids for a possible synergism between AC
      and the pesticides.

PMID- 30094244
TI  - Quality in gastrointestinal endoscopy: the preface.

PMID- 30094243
TI  - The Distribution of Bovine Tuberculosis in Cattle Farms Is Linked to Cattle Trade
      and Badger-Mediated Contact Networks in South-Western France, 2007-2015.
AB  - Bovine tuberculosis (bTB), mainly caused by Mycobacterium bovis, can affect
      domestic and wild animals as well as humans. Identifying the major transmission
      mechanisms in an area is necessary for disease control and management. In this
      study, we aimed to evaluate the involvement of different types of contact in M.
      bovis transmission between cattle farms of south-western France between 2007 and
      2015. We analyzed an empirical contact network of cattle farms as nodes, with
      known infection status and molecular types (16 circulated during the study period
      of which 14 affected only cattle and two both badgers and cattle). Edges were
      based on cattle trade data (T-edges) and on spatial neighborhood relationships
      between farms, either direct (P-edges) or badger-mediated, when two farms
      neighbored the same badger home range (B-edges), or two distinct but neighboring
      badger home ranges (D-edges). Edge types were aggregated so that the contact
      network contained only unique edges labeled by one or several edge types. The
      association between the contact network structure and bTB infection status was
      assessed using a non-parametric test, each molecular type being considered a
      marker of an independent epidemic. Using a logistic regression model, we
      estimated the contribution of each edge type to the probability for an edge
      originating from an infected farm to end at another infected farm. A total number
      of 1946 cattle farms were included in the study and were linked by 54,243 edges.
      Within this contact network, infected farms (whatever the molecular type) always
      belonged to the same component, suggesting the contact network may have supported
      bTB spread among those farms. A significant association between the pattern of
      bTB-infected farms and the structure of the contact network was observed when all
      the molecular types were simultaneously considered. The logistic regression model
      showed a significant association between M. bovis infection in direct neighbors
      of infected farms and the connection by T-, B- and D-edges, with odds-ratios of
      7.4, 1.9, and 10.4, respectively. These results indicate a multifactorial M.
      bovis transmission between cattle farms of the studied area, with varying
      implication levels of the trade, pasture and badger networks according to the
      molecular type.

PMID- 30094245
TI  - Critical appraisal of guidelines for screening and surveillance of Barrett's
      esophagus.
AB  - Esophageal adenocarcinoma (EAC) arising on Barrett esophagus (BE) has become the
      most frequent type of esophageal malignancy in the Western world. BE is a
      frequent condition but progression to EAC is rare. Scientific societies publish
      guidelines in order to improve patients' care. However, there are fields where
      evidence is lacking or there are many controversies. We aimed to spotlight the
      most important changes, as well as the points of controversy in the recently
      published guidelines for BE. For most, a length >=1 cm of a salmon-pink mucosa
      extending above the eso-gastric junction is required in order to define BE,
      accompanied with the presence of intestinal metaplasia (IM) at histology.
      Screening with endoscopy for the general population is not recommended while
      there is no proof of the efficacy of screening for targeted high risk
      populations. New techniques permitting a cytologic examination are under
      evaluation and may change this strategy. The use of high-resolution endoscopes
      coupled with a careful inspection of the mucosa are required during surveillance
      of BE. New studies are necessary in order to clarify the real benefit from the
      use of advanced techniques, such as virtual chromoendoscopy. Length of non
      dysplastic BE plays a role for the interval time determination between
      endoscopies during surveillance. Indefinite for dysplasia and even more low grade
      dysplasia (LGD) are debatable issues in the matter of BE. There are compelling
      data suggesting that a definite LGD, defined as a permanent lesion confirmed by a
      specialist pathologist in BE, has a more dismal prognosis than previously
      reported and an ablative intervention may be offered in this case. However, most
      (75-85%) cases with LGD were downstaged in published studies and it remains
      unknown if in real life, percentages of downstaging are approaching those of
      studies or there is an over-treatment of pseudo-LGD. Biomarkers such as p53
      immunohistochemistry may aid better identification of patients at higher risk.
      For high grade dysplasia (HGD) visible lesions should be resected with Endoscopic
      Mucosal Resection (EMR) while flat lesions ablated, for most, nowadays, with
      radiofrequency ablation (RFA). Endoscopic submucosal dissection (ESD) has not
      proved superior compared to EMR in BE. It has to be underlined that most studies
      leading to the new guidelines for BE are not considered of high quality and new
      guidelines may emerge in the near future.

PMID- 30094248
TI  - Ten quality indicators for endoscopic submucosal dissection: what should be
      monitored and reported to improve quality.
AB  - In the last decade, endoscopic submucosal dissection (ESD) has become more
      popular in Asia and, more recently, also in Europe and North America, however the
      issue of quality control has never been raised. Therefore, there is an urgent
      need to identify possible quality indicators to monitor as part of internal audit
      process. This is particularly compelling, since the diffusion of ESD outside
      Asian, super-expert, high-volume, tertiary referral centers. In the current
      review, we raised the issue of quality control for ESD and proposed a list of ten
      possible quality indicators that should be monitored by each endoscopist and
      reported in every study reporting results on ESD procedures. We feel that these
      quality indicators should be used in clinical practice by endoscopists to
      benchmark the data with the internationally recommended standards.

PMID- 30094247
TI  - Quality in upper gastrointestinal endoscopic submucosal dissection.
AB  - Progress in the endoscopy technology field led to an increase in the diagnosis of
      early gastrointestinal (GI) superficial lesions and to an improvement of their
      treatment. Endoscopic submucosal dissection (ESD) has been developed in Japan
      with the aim of removing such lesions in one piece, in order to obtain a curative
      resection and to minimize the risk of local recurrence, and to preserve the
      native organ. ESD is widely used in Asia for the treatment of early upper and
      lower GI lesions and is currently gaining attention in Western countries too.
      However, ESD can be safely performed only by expert endoscopists and in specific
      clinical settings. Therefore, prior to decide whether ESD is feasible or not, the
      target lesion must be carefully assessed, in order to understand whether or not
      it is eligible for submucosal dissection. The aim of this paper is to review
      indications, limitations and technical aspects of upper GI ESD.

PMID- 30094246
TI  - What defines quality in small bowel capsule endoscopy.
AB  - Small bowel capsule endoscopy is considered a first-line diagnostic tool for the
      investigation of small bowel diseases. Gastroenterological and endoscopic
      societies have proposed and established measures known as quality indicators,
      quality measures or performance measures for the majority of endoscopic
      procedures, in order to ensure competence, healthcare quality and define areas
      requiring improvement. However, there is a paucity of publications describing
      small bowel capsule endoscopy quality indicators. Hereby, we attempt to identify
      and describe a number of pre-procedure, intra-procedure and post-procedure
      quality indicators, regarding process measures in small bowel capsule endoscopy,
      after a comprehensive review of the literature.

PMID- 30094250
TI  - Quality in endoscopy training-the endoscopic retrograde cholangiopancreatography
      case.
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most advanced
      therapeutic procedures in gastrointestinal endoscopy. It is highly operator
      dependent procedure requiring specific, knowledge-based training in order to
      achieve competence. Strategies for assessing competency of trainees and those in
      practice include numbers of procedures performed, and subjective or objective
      assessment by a mentor or self-assessment by the trainee. However, it is still
      not clear how to measure the quality in (ERCP) training in an objective and
      reproducible way, so far. Thus, in this article, we will discuss issues related
      to training in ERCP and provide experience based discussion on how to best
      approach and master this complex and risky procedure.

PMID- 30094249
TI  - Monitoring of colonoscopy quality indicators in an academic endoscopy facility
      reveals adherence to international recommendations.
AB  - Background: We monitor colonoscopy service quality biannually, by measuring
      sedation administration, colonoscopy completion, adenoma detection and early
      complications rates (CR). We herein present our audit results for the years 2013
      and 2015. Methods: In our endoscopy facility, five rotating senior
      gastroenterologists perform colonoscopies, on a daily basis. We measured the
      quality indicators in three cohorts: A, intention for total colonoscopy cases; B,
      cohort A excluding bowel obstruction cases; C, colorectal cancer (CRC) screening
      cases. Results: In 2015, overall sedation administration rate (SAR) was 93.0%
      (91.6-94.4%), achieving our target to give conscious sedation to >90% of patients
      undergoing colonoscopy in all three cohorts. Colonoscopy completion rate (CCR)
      increased significantly (P<0.0001) from 94.8% (93.4-96.2%) to 98.1% (97.3-98.9%)
      in cohort B and numerically from 96.6% (94.4-98.8%) to 98.6% (97.4-99.7%) in
      cohort C, at the same periods. In cohort C, adenoma detection rates (ADR) were
      similar-27.1% (21.7-32.5%) and 27% (22.7-31.3%)-in the two periods. There were
      only two serious early complications: one cardiorespiratory event and one
      perforation in 2013 and 2015, respectively. While significant variability
      regarding SAR (ranging from 80% to 100%) was detected among the participating
      endoscopists, all but one of them constantly achieved [judged by the lower
      confidence interval (CI) of the quality indicator] CCRs higher than the
      recommended by international guidelines. On the contrary ADR was variable among
      endoscopists during the studied periods. Conclusions: Although there is certain
      variability in endoscopists' performance, the overall colonoscopy quality
      indicators meet or exceed the internationally recommended standards, in our
      endoscopy facility.

PMID- 30094251
TI  - How to measure quality in endoscopic retrograde cholangiopancreatography (ERCP).
AB  - Endoscopic retrograde cholangiopancreatography (ERCP) is invasive therapeutic
      procedure demanding specific individual approach for learning and mastering. It
      is associated with greater morbidity and mortality than any other procedure in
      gastroenterology. The risk for complications and harm for patient inevitably
      require strict guidelines to be followed regarding training, certification and
      proficiency. In an attempt to reduce the risk of complications, various
      endoscopic societies worldwide have established so called "Quality measures"
      which proved to be the back bone for safety and quality in ERCP. Recently
      developed ERCP quality network allowing data comparison between endoscopist is
      the key of reducing complications and creating a state of the art teaching
      program for beginner endoscopist. Further research is required regarding quality
      measures improvement and information exchange in the global ERCP quality network.

PMID- 30094252
TI  - How to measure quality in endoscopic ultrasound.
AB  - Quality is a key focus for gastrointestinal endoscopy and main international
      gastroenterology societies instituted specific task forces focused on this issue.
      Endoscopic ultrasound (EUS) represents one of the most fascinating fields to
      explore in gastrointestinal endoscopy due to its relatively limited availability
      out of high-volume centers. This leads to a particular need to define widely
      accepted quality indicators (QIs) and the ways to measure them. The current
      manuscript reviews these indicators in light of their impact on common clinical
      practice.

PMID- 30094253
TI  - Full spectrum endoscopy for an easy and adequate visualization of Vater's
      papilla.
AB  - Patients with classical familial adenomatous polyposis (FAP) are at high risk for
      developing colorectal cancer (CRC) and duodenal adenomas. Current guidelines
      recommend to start duodenal screening at the age of 25-30 years and standard
      upper gastrointestinal (GI) endoscopy is considered inadequate for an optimal
      visualization of the duodenum. We used the Full-Spectrum Endoscopy(r) (FUSE(r);
      EndoChoice Inc., Atlanta, GA, USA) esophagogastroduodenoscope (FUSE-EGD) for an
      upper GI screening procedure of a 20-year-old Caucasian male with classical FAP.
      The pioneer design of the FUSE-EGD allowed an easy and accurate examination of
      the ampulla with standard scope manipulation maneuvers.

PMID- 30094254
TI  - Adhering to quality medical care: a case report of upper gastrointestinal
      bleeding due to self-expandable metal stent placed for benign duodenal
      obstruction.
AB  - Endoscopic placement of self-expandable metal stent (SEMS) is an efficient method
      for the palliative decompression of malignant gastro duodenal obstruction.
      However, its role in treating benign obstructive conditions is controversial. We
      herein present an unusual case of recurrent upper gastrointestinal (GI) bleeding
      episodes due to ischemic lesions induced by an uncovered SEMS placed several
      years before to treat post peptic ulcer pyloric obstruction. Patient's advanced
      age precluded any attempt for endoscopic or surgical removal of the stent and the
      patient was successfully treated only with proton pump inhibitors, remaining
      uneventful on the long term. This case speaks to the need for rational use of
      innovative treatment modalities for quality of care provision.

PMID- 30094256
TI  - Health-related quality of life measure distinguishes between low and high
      clinical T stages in esophageal cancer.
AB  - Background: Functional Assessment of Cancer Therapy-Esophagus (FACT-E) is a
      health-related quality of life (HRQOL) instrument validated in patients with
      esophageal cancer. It is made up of both a general component and an esophageal
      cancer subscale (ECS). Our objective was to explore the relationship between
      baseline FACT-E, ECS and clinically determined T-stage in patients with stage II
      IV cancer of the gastroesophageal junction or thoracic esophagus. Methods: Data
      from four prospective studies in Canadian academic hospitals were combined. These
      were consecutive and eligible patients treated between 1996 and 2014 with
      clinical stage II-IV cancer of the gastroesophageal junction or thoracic
      esophagus. All patients completed pre-treatment FACT-E. Parametric (ANOVA) and
      non-parametric (Kruskal-Wallis) analyses were performed. Results: Of the 135
      patients that were deemed eligible, the T-stage distribution determined
      clinically was: 10 (7.4%) T1, 33 (24.4%) T2, 79 (58.5%) T3 and 13 (9.6%) T4.
      Parametric analysis showed no significant association between FACT-E & T-stage,
      although there was a trend towards significance (P=0.08). Non-parametric analysis
      showed a significant association between FACT-E and T-stage (P=0.05). Post-hoc
      tests identified that the most significant differences in FACT-E scores were
      between T1 and T3 patients. Both parametric (P=0.002) and non-parametric
      (P=0.003) analyses showed an association between ECS & T-stage. Post-hoc analyses
      showed significant differences in ECS scores between T1 and higher T-stages
      (P<0.01). Conclusions: Patient-reported HRQOL scores appear to be significantly
      different in patients with clinical T1 esophageal cancer as compared to those
      with higher clinical T stages. Since distinguishing T1 from T2/T3 lesions is
      important in guiding the most appropriate treatment modality and since EUS
      appears to have difficulties reliably making such T-stage distinctions, FACT-E
      and ECS scores may be helpful as an adjunct to guide decision-making.

PMID- 30094255
TI  - Use of lung-protective strategies during one-lung ventilation surgery: a multi
      institutional survey.
AB  - Background: Limited evidence suggests that intraoperative lung-protective
      ventilation (LPV) during one-lung ventilation (OLV) may reduce respiratory
      complications after thoracic surgery. Little is known about LPV practices during
      OLV. Our purpose was to assess the state of practice/perspectives of
      anesthesiologists regarding LPV during elective OLV. Methods: We conducted a
      multi-institutional cross-sectional survey of anesthesiologists performing OLV at
      high-volume Canadian tertiary/university centers. The survey was designed,
      refined and distributed by a multi-disciplinary team using the Dillman method.
      Univariable and multivariable analyses were used. Results: Seventy-five (63%) of
      120 eligible respondents completed the survey. Although the critical care
      literature focuses on minimizing tidal volume (TV) as the central strategy of
      LPV, most respondents (89%, n=50/56) focused on minimizing peak airway pressure
      (PAP) as their primary strategy of intraoperative LPV. Only 64% (n=37/58)
      reported actively trying to minimize TV. While 32% (n=17/54) were unsure about
      the current evidence regarding LPV, 67% (n=36/54) believed that the evidence
      favoured their use during OLV. Perceived clinical and institutional barriers were
      the only predictors of reduced attempts to minimize TV on univariate analyses. In
      multivariable/adjusted analyses, perceived institutional barriers were the only
      predictors of reduced attempts to minimize TV with adjusted odds ratio of 0.1
      (95% CI: 0.03-0.6). Conclusions: Most anesthesiologists defined low PAP as the
      primary strategy of LPV during OLV and attempted to minimize it. This study is
      the first to assess the practice/perspectives of anesthesiologists regarding LPV
      during OLV and also the first to explore predictors of LPV use. Randomized trials
      are currently ongoing. However, this study suggests that institutional barriers
      may subvert future knowledge translation and need to be addressed.

PMID- 30094257
TI  - DUSP2 methylation is a candidate biomarker of outcome in head and neck cancer.
AB  - Background: Biomarkers predictive of response to chemoradiotherapy (CRT) regimens
      for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are
      urgently required to identify patients in whom this approach is likely to be
      effective. TP53 mutations and epidermal growth factor (EGFR) overexpression are
      common markers of disease. Dual-specificity-phosphatase-2 (DUSP2) has an
      essential role in cell proliferation, cancer and immune responses. Methods:
      Aberrant DUSP2 methylation was investigated by pyrosequencing in 5 HNSCC cell
      lines, 112 LA-HNSCC tumours. EGFR was investigated by immunohistochemistry and
      TP53 was analysed by sequencing. Results: We demonstrate methylation-dependent
      transcriptional silencing of DUSP2 in HNSCC cell lines. In LA-HNSCC patients,
      aberrant methylation in the DUSP2 CpG island was present in 51/112 cases (45.5%).
      LA-HNSCC cases with wild-type TP53, overexpression of EGFR and unmethylated DUSP2
      had the worst overall survival (P<=0.001). Conclusions: DUSP2 methylation, when
      combined with EGFR and TP53, is a candidate biomarker of clinical outcome in LA
      HNSCC treated with CRT.

PMID- 30094259
TI  - Professor Sebastian Brandner: the next frontiers of molecular diagnostics of
      brain tumours-interrogating epigenetic profiles of brain tumours.

PMID- 30094258
TI  - Management of ruptured liver segment IV hepatocellular carcinoma: is
      transarterial embolization (TAE) superior to chemoembolization (TACE)?-the jury
      is still out.
AB  - HCC rupture is a potentially life-threatening complication owing to underlying
      vascular dysfunction and coagulopathy. There is still a debate in the literature
      concerning the best approach in patients presenting in the emergency setting with
      shock due to spontaneous HCC rupture. In the current report, we describe the case
      of a 66-year-old female patient with ruptured HCC who was treated successfully by
      emergency transarterial embolization (TAE) with complete response proved by
      gradual shrinkage of the tumor. This impressive complete response suggests that
      TAE followed by elective hepatectomy could be an efficient approach for patients
      with Child-Pugh class A liver function and adequate liver remnant. More studies
      are needed in order to construct specific guidelines for the treatment of rHCC
      that will be based on the disease severity and the patient status.

PMID- 30094260
TI  - Professor Bing Peng: there is no shortcut to anywhere you want to go.

PMID- 30094261
TI  - "Remote" myokine protects from pulmonary ischemia/reperfusion injury by a
      surprising "proximal" control mechanism.

PMID- 30094262
TI  - The role of dobutamine stress echocardiography based projected aortic valve area
      in assessing patients with classical low-flow low-gradient aortic stenosis.

PMID- 30094263
TI  - Suppression of monocyte inflammatory and coagulopathy responses in HIV infection.

PMID- 30094265
TI  - DIAMOND study: an additional evidence of the interest of being proactive in IBD.

PMID- 30094264
TI  - Is there a beneficial effect of adding azathioprine to adalimumab in Crohn's
      disease patients?

PMID- 30094266
TI  - Telomere length: is the future in our "ends"?
AB  - Telomeres, repetitive nucleotide sequences located at the end of each chromosome,
      play the important function of preserving chromosome stability and preventing
      molecular contact with neighboring chromosomes. Albeit the concept that telomere
      length may be a marker of health and disease seems hence counterintuitive, the
      translation of this clear-cut concept from the bench to the beside has appeared
      so far less straightforward. In particular, controversial evidence has emerged so
      far about the fact that telomere length may actually predict morbidity and
      mortality across many clinical settings. This uncertainty is actually due to a
      kaleidoscope of biological and technical factors, including preanalytical issues
      (e.g., sample matrix), poor standardization of techniques used for their
      assessment, and dependence of telomere structure upon genetics, epigenetics,
      environment and behavioral attitudes, which may be present at a variable extent
      in various physiological or pathological conditions. Therefore, although it is
      now undeniable that our future is largely in our "hands" (i.e., genotype, diet,
      exposure to environmental factors and so forth), larger and more solid evidence
      will be necessary before concluding that the future is also written in our
      (chromosome) "ends".

PMID- 30094267
TI  - Distraction ligamentotaxis for complex proximal interphalangeal joint fracture
      dislocations: a clinical study and the modified pins rubber band traction system
      revisited.
AB  - Background: The purpose of this study is to present our experience with the
      modified pins and rubber band traction system, discuss problems encountered, and
      make recommendations to optimize outcomes. Methods: Data was collected
      prospectively from November 2013 to March 2017 at a tertiary referral hospital in
      Melbourne, Australia. Patients with closed complex proximal interphalangeal joint
      fracture dislocations that were considered unsuitable for other surgical options
      were included in the study. Patients underwent dynamic skeletal distraction using
      the modified (Deshmukh) pins rubber band traction system. Outcomes were measured
      using the Nominal Rating Scale for pain; Disabilities of the Arm, Shoulder, and
      Hand (DASH) score; active and passive range of motion; patient rating scale; and
      complications. Results: Twenty patients underwent the procedure, and 19 were
      included in analyses. At the final follow-up assessment, an average of 62 degrees
      and 77 degrees  was achieved for proximal interphalangeal joint active and
      passive range of motion, respectively. Pain levels were low (median score of 0 at
      rest and 1 ranging, out of 10). Four patients suffered minor pin site infections.
      Conclusion: Distraction ligamentotaxis is a useful part of the armamentarium,
      especially in the absence of more suitable procedures. It is important to select
      appropriate patients, educate, and ensure adherence to postoperative therapy.
      Employing the Deshmukh frame modification streamlines the theatre processes, and
      removal of wires at approximately 4 weeks minimizes risk of pin site infection.

PMID- 30094268
TI  - Simultaneous Bilateral Spontaneous Pneumothorax in an Adult Patient With
      Pulmonary Langerhans Cell Histiocytosis: A Case Report.
AB  - We report a case of a young female with known history of pulmonary Langerhans
      cell histiocytosis who was initially presented in the emergency department of a
      university hospital with respiratory distress. Clinical assessment and diagnostic
      workup revealed left hemithorax subcutaneous emphysema, bilateral pneumothorax,
      and atelectasis in both lower lung lobes. The patient was treated with bilateral
      staged thoracoscopic bullectomy and mechanical abrasion of the parietal pleura
      combined with chemical pleurodesis with talc. A new occurrence of right-sided
      pneumothorax was noticed 3 days after surgery, which was treated with chest tube
      insertion and chemical pleurodesis. The aforementioned surgical approach resulted
      in complete lung expansion and the patient's full recovery. A review of pulmonary
      Langerhans cell histiocytosis and treatment options in cases of pneumothorax due
      to lung histiocytosis is also presented in this report.

PMID- 30094269
TI  - Magnetic Resonance Imaging Parameters at 1 Year Correlate With Clinical Outcomes
      Up to 17 Years After Autologous Chondrocyte Implantation.
AB  - Background: The ability to predict the long-term success of surgical treatment in
      orthopaedics is invaluable, particularly in clinical trials. The quality of
      repair tissue formed 1 year after autologous chondrocyte implantation (ACI) in
      the knee was analyzed and compared with clinical outcomes over time. Hypothesis:
      Better quality repair tissue and a better appearance on magnetic resonance
      imaging (MRI) 1 year after ACI lead to improved longer-term clinical outcomes.
      Study Design: Cohort study; Level of evidence, 3. Methods: Repair tissue quality
      was assessed using either MRI (11.5 +/- 1.4 [n = 91] or 39.2 +/- 18.5 [n = 76]
      months after ACI) or histology (16.3 +/- 11.0 months [n = 102] after ACI). MRI
      scans were scored using the whole-organ magnetic resonance imaging score (WORMS)
      and the magnetic resonance observation of cartilage repair tissue (MOCART) score,
      with additional assessments of subchondral bone marrow and cysts. Histology of
      repair tissue was performed using the Oswestry cartilage score (OsScore) and the
      International Cartilage Repair Society (ICRS) II score. Clinical outcomes were
      assessed using the modified Lysholm score preoperatively, at the time of MRI or
      biopsy, and at a mean 8.4 +/- 3.7 years (maximum, 17.8 years) after ACI. Results:
      At 12 months, the total MOCART score and some of its individual parameters
      correlated significantly with clinical outcomes. The degree of defect fill,
      overall signal intensity, and surface of repair tissue at 12 months also
      significantly correlated with longer-term outcomes. The presence of cysts or
      effusion (WORMS) significantly correlated with clinical outcomes at 12 months,
      while the presence of synovial cysts/bursae preoperatively or the absence of
      loose bodies at 12 months correlated significantly with long-term clinical
      outcomes. Thirty percent of repair tissue biopsies contained hyaline cartilage,
      65% contained fibrocartilage, and 5% contained fibrous tissue. Despite no
      correlation between the histological scores and clinical outcomes at the time of
      biopsy, a lack of hyaline cartilage or poor basal integration was associated with
      increased pain; adhesions visible on MRI also correlated with significantly
      better histological scores. Conclusion: These results demonstrate that MRI at 12
      months can predict longer-term clinical outcomes after ACI. Further investigation
      regarding the presence of cysts, effusion, and adhesions and their relationship
      with histological and clinical outcomes may yield new insights into the
      mechanisms of cartilage repair and potential sources of pain.

PMID- 30094270
TI  - Predictors of Pain and Functional Outcomes After the Nonoperative Treatment of
      Rotator Cuff Tears.
AB  - Background: Optimal patient selection is key to the success of nonoperative
      treatment for rotator cuff tears. Purpose: To assess the predictors of pain and
      functional outcomes in a longitudinal cohort of patients undergoing nonoperative
      treatment. Study Design: Cohort study; Level of evidence, 2. Methods: A
      multicenter cohort of patients with rotator cuff tears undergoing nonoperative
      treatment was recruited from March 2011 to February 2015. Patients completed a
      detailed health questionnaire, completed standardized shoulder questionnaires
      including the Shoulder Pain and Disability Index (SPADI), and underwent magnetic
      resonance imaging. In addition to baseline assessments, patients received follow
      up questionnaires at 3, 6, 12, and 18 months. Longitudinal mixed models were used
      to test predictors of the SPADI score, and interactions with time were assessed.
      Results: In our cohort of 70 patients, being married as compared with being
      single/divorced/widowed (P = .02), a shorter duration of symptoms (P = .02),
      daily shoulder use at work that included light or no manual labor versus moderate
      or heavy manual labor (P = .04), alcohol use of 1 to 2 times per week or more as
      compared with 2 to 3 times per month or less (P = .007), and absence of fatty
      infiltration (P = .0009) were significantly associated with decreased SPADI
      scores (improved shoulder pain and disability) over time. When interactions with
      time were assessed, having a college level of education or higher compared with
      less than a college education showed a differential effect over time, with those
      with a college level of education or more having lower SPADI scores (P = .004).
      Partial-thickness tear versus full-thickness tear also had an interaction with
      follow-up duration, such that those with a partial-thickness tear had lower SPADI
      scores (P = .0002). Conclusion: Longitudinal predictors of better outcomes of the
      nonoperative treatment of rotator cuff tears included being married, having at
      least a college education, shorter duration of symptoms, light or manual labor in
      daily work, alcohol use of 1 to 2 times per week or more, partial-thickness tear,
      and absence of fatty infiltration of the rotator cuff. Our results suggest that
      nonoperative treatment should be performed early for optimal outcomes. These data
      can be used to select optimal candidates for the nonoperative treatment of
      rotator cuff tears and to assist with patient education and expectations before
      treatment.

PMID- 30094271
TI  - Patient- and Procedure-Specific Variables Driving Total Direct Costs of
      Outpatient Anterior Cruciate Ligament Reconstruction.
AB  - Background: Few studies have investigated the influence of patient-specific
      variables or procedure-specific factors on the overall cost of anterior cruciate
      ligament reconstruction (ACLR) in an ambulatory surgery setting. Purpose: To
      determine patient- and procedure-specific factors influencing the overall direct
      cost of outpatient arthroscopic ACLR utilizing a unique value-driven outcomes
      (VDO) tool. Study Design: Cohort study (economic and decision analysis); Level of
      evidence, 3. Methods: All ACLRs performed by 4 surgeons over 2 years were
      retrospectively reviewed. Cost data were derived from the VDO tool. Patient
      specific variables included age, body mass index, comorbidities, American Society
      of Anesthesiologists (ASA) classification, smoking status, preoperative Patient
      Reported Outcomes Measurement Information System (PROMIS) Physical Function
      Computerized Adaptive Testing (PF-CAT) score, and preoperative Single Assessment
      Numeric Evaluation (SANE) score. Procedure-specific variables included graft
      type, revision status, associated injuries and procedures, time from injury to
      ACLR, surgeon, and operating room (OR) time. Multivariate analysis determined
      patient- and procedure-related predictors of total direct costs. Results: There
      were 293 autograft reconstructions, 110 allograft reconstructions, and 31 hybrid
      reconstructions analyzed. Patient-specific factors did not significantly
      influence the ACLR cost. The mean OR time was shorter for allograft
      reconstruction (P < .001). Predictors of an increased direct cost included the
      use of an allograft or hybrid graft (44.5% and 33.1% increase, respectively; P <
      .001), increased OR time (0.3% increase per minute; P < .001), surgeon 3 or 4
      (9.1% or 5.9% increase, respectively; P < .001 or P = .001, respectively), and
      concomitant meniscus repair (24.4% increase; P < .001). Within the meniscus
      repair cohort, all-inside, root, and combined repairs correlated with a 15.5%,
      31.4%, and 53.2% increased mean direct cost, respectively, compared with inside
      out repairs (P < .001). Conclusion: This study failed to identify modifiable
      patient-specific factors influencing direct costs of ACLR. Allografts and hybrid
      grafts were associated with an increased total direct cost. Meniscus repair
      independently predicted an increased direct cost, with all-inside, root, and
      combined repairs being costlier than inside-out repairs. The time-saving
      potential of all-inside meniscus repair was not realized in this study, making
      implant use a significant factor in the overall cost of ACLR with meniscus
      repair.

PMID- 30094273
TI  - The development of methods to measure exposure to a major rabbit allergen (Ory c
      1).
AB  - Rabbits are used as laboratory animal models and are also popular domestic pets.
      Allergic responses to rabbit allergens have been documented in both settings, and
      several rabbit allergens identified. We have purified an 18 kD protein extracted
      from rabbit fur that was shown by N-terminal sequencing and mass spectrometry
      (MS) to be a lipocalin, identical to that identified as an odorant binding
      protein and an allergen with the formal nomenclature of Ory c 1. De novo
      sequencing of the MS peptide fragments gave additional primary sequence data of
      this protein. Polyclonal antisera were raised against the purified protein and
      used to develop two types of immunoassay. Ory c 1 content was measured in used
      rabbit bedding and household dust samples from homes keeping rabbits as pets.
      Atmospheric sampling was also undertaken in an animal facility undertaking rabbit
      experimental work. Ory c 1 levels in house dust where rabbits were kept as pets
      were between undetectable-41,290 ng.g-1, and in used bedding between 370-26,740
      ng.g-1. Significantly higher house dust levels were found where rabbits spent
      large amounts, or all of, their time indoors. Personal air sampler levels within
      the animal facility were between 65-216 ng.m-3. Low levels (0.8-2 ng.m-3) were
      found in the facility's changing rooms, but undetected in the entrance lobby,
      office and laundry. We believe that these immunochemical assays may be used to
      identify activities in the occupational and domestic setting which produce higher
      levels of exposure to rabbit allergens, and where measures to control exposure
      may be warranted to reduce potential risk of allergic outcomes.

PMID- 30094274
TI  - Individual movements and contact patterns in a Canadian long-term care facility.
AB  - Contact networks of individuals in healthcare facilities are poorly understood,
      largely due to the lack of spatio-temporal movement data. A better understanding
      of such networks of interactions can help improve disease control strategies for
      nosocomial outbreaks. We sought to determine the spatio-temporal patterns of
      interactions between individuals using movement data collected in the largest
      veterans long-term care facility in Canada. We processed close-range contact data
      generated by the exchange of ultra-low-power radio signals, in a prescribed
      proximity, between wireless sensors worn by the participants over a two-week
      period. Statistical analyses of contact and movement data were conducted. We
      found a clear dichotomy in the contact network and movement patterns between
      residents and healthcare workers (HCWs) in this facility. Overall, residents tend
      to have significantly more distinct contacts with the mean of 17.3 (s.d. 3.6)
      contacts, versus 3.5 (s.d. 2.3) for HCWs (p-value < 10-12), for a longer duration
      of time (with mean contact duration of 8 minutes for resident-resident pair
      versus 4.6 minutes for HCW-resident pair) while being less mobile than HCWs.
      Analysis of movement data and clustering coefficient of the hourly aggregated
      network indicates that the contact network is loosely connected (mean clustering
      coefficient: 0.25, interquartile range 0-0.40), while being highly structured.
      Our findings bring quantitative insights regarding the contact network and
      movements in a long-term care facility, which are highly relevant to infer direct
      human-to-human and indirect (i.e., via the environment) disease transmission
      processes. This data-driven quantification is essential for validating disease
      dynamic models, as well as decision analytic methods to inform control strategies
      for nosocomial infections.

PMID- 30094272
TI  - Comparing imaging capabilities of spectral domain and swept source optical
      coherence tomography angiography in healthy subjects and central serous
      retinopathy.
AB  - Background: There are two forms of system implementation of optical coherence
      tomography angiography (OCTA) in ophthalmic imaging, i.e., spectral domain (SD-)
      and swept source OCTA (SS-OCTA). The purpose of this paper is to compare the SD
      OCTA and SS-OCTA for elucidating structural and vascular features associated with
      central serous retinopathy (CSR), and to evaluate the effects of CSR on SD- and
      SS-OCTA's imaging capabilities. Methods: Normal subjects and CSR patients were
      imaged by SD- and SS-OCTA using 3 * 3 mm and 6 * 6 mm scan patterns. OCT signal
      strengths at the superficial retina, deep retina, Sattler's layer and Haller's
      layer were used to compare the ability of SD- and SS-OCTA to image structural
      features. In addition, the ability to acquire angiograms were discussed by
      evaluating retinal vessel density. Central serous volume (CSV) was measured and
      it was correlated with difference in signal strengths (?S) between two OCTA
      devices. Results: Seven normal eyes and seven diseased eyes were recruited.
      Results showed no significant differences between SD- and SS-OCT in detecting
      structural features of the retinal layer according to the paired t-test. However,
      when imaging the Sattler's layer for normal eyes, a significant difference is
      found between SD- and SS-OCT (p < 0.0001 for 3 * 3 mm scan, and p = 0.0002 for 6
      * 6 mm); while for CSR eyes, the corresponding values were p < 0.0001 and p =
      0.0003, respectively. At Haller's layer for normal eyes, the corresponding values
      were p = 0.0004 and p = 0.0014; and for CSR eyes, p = 0.0004 and p < 0.0001,
      respectively. A strong correlation between ?S and CSV was observed in the
      Sattler's layer (3 * 3 mm - p = 0.0031 and R2  = 0.951; 6 * 6 mm - p = 0.0075 and
      R2  = 0.911) and Haller's layer (3 * 3 mm - p = 0.0026 and R2  = 0.955; 6 * 6 mm 
      p = 0.0013 and R2  = 0.972). Conclusions: The results suggest no differences
      between SD- and SS-OCTA for imaging the retinal layers however, when imaging
      beyond retinal layers, SS-OCTA appears advantageous in detecting returning
      signals. In CSR cases, the CSV may have an impact on sub-CSR tissue imaging and
      appears to have more impact on SD- than SS-OCTA.

PMID- 30094275
TI  - African American women perceptions of physician trustworthiness: A factorial
      survey analysis of physician race, gender and age.
AB  - Background/Objective: Physical concordance between physicians and patients is
      advocated as a solution to improve trust and health outcomes for racial/ethnic
      minorities, but the empirical evidence is mixed. We assessed women's perceptions
      of physician trustworthiness based on physician physical characteristics and
      context of medical visit. Methods: A factorial survey design was used in which a
      community-based sample of 313 African American (AA) women aged 45+ years
      responded to vignettes of contrived medical visits (routine versus serious
      medical concern visit) where the physician's race/ethnicity, gender, and age were
      randomly manipulated. Eight physician profiles were generated. General linear
      mixed modeling was used to assess separately and as an index, trust items of
      fidelity, honesty, competence, confidentiality, and global trust. Trust scores
      were based on a scale of 1 to 5, with higher scores indicating higher trust. Mean
      scores and effect sizes (ES) were used to assess magnitude of trust ratings.
      Results: No significant differences were observed on the index of trust by
      physician profile characteristics or by medical visit context. However, the white
      older-male was rated higher than the AA-older-female on fidelity (4.23 vs. 4.02;
      ES = 0.215, 95% CI: 0.001-0.431), competence (4.23 vs. 3.95; ES = 0.278, 95% CI:
      0.062-0.494) and honesty (4.39 vs. 4.19, ES = 0.215, 95% CI: 0.001-0.431). The AA
      older male was rated higher than the AA-older-female on competence (4.20 vs.
      3.95; ES = 0.243, 95% CI: 0.022-0.464) and honesty (4.44 vs. 4.19; ES = 0.243,
      95% CI: 0.022-0.464). The AA-young male was rated higher than AA-older-female on
      competence (4.16 vs. 3.95; ES = 0.205, 95% CI: 0.013-0.423). Conclusions:
      Concordance may hold no salience for some groups of older AA women with regards
      to perceived trustworthiness of a physician. Policies and programs that promote
      diversity in the healthcare workforce in order to reduce racial/ethnic
      disparities should emphasize cultural competency training for all physicians,
      which is important in understanding patients and to improving health outcomes.

PMID- 30094276
TI  - Paediatric acute rheumatic fever in developed countries: Neglected or negligible
      disease? Results from an observational study in Lombardy (Italy).
AB  - Introduction: Acute Rheumatic Fever (ARF) is a multisystemic disease that results
      from an autoimmune reaction due to group A streptococcal infection. The disease
      affects predominantly children aged 5 to 15 years and although its incidence in
      developed Countries declined since the early 1900s, to date there is a paucity of
      data that confirm this epidemiological trend. Objective: The study aimed to
      assess the burden of ARF in term of hospitalization and to describe the
      characteristics of acute rheumatic fever (ARF) in the paediatric population of
      Lombardy. Study design: The study was carried out by analyzing hospital discharge
      records of patients resident of Lombardy and aged 0-17 years old who, from 2014
      to 2016, were hospitalized with the diagnosis of ARF. The following variables
      have been studied: age, sex, municipality of residence, date of diagnosis of each
      patient, hospital of admission, and presentation of the disease. Results: From
      2014 to 2016, 215 patients were found to meet the inclusion criteria and
      diagnosed as affected from Acute Rheumatic Fever. The rate of hospitalization
      showed a slightly increasing trend from 3.42 in 2014 to about 5.0 in 2016.
      Moreover, ARF presented a typical seasonal trend with lower cases in the autumn
      and a peak of hospitalization in the spring. Conclusion: To date, ARF seems to be
      a rare but not negligible disease in southern central European countries, and in
      Lombardy we estimated an annual hospitalization rate of 4.24 cases per 100,000
      children. The increasing trend found in our study suggests that the burden of the
      disease could be reduced by involving multidisciplinary health professionals who,
      in addition to the paediatrician of free choice, would promote evidence based
      medicine management of the disease during all its clinical phases.

PMID- 30094277
TI  - Estimating physical activity trends among blacks in the United States through
      examination of four national surveys.
AB  - Physical activity is essential for overall good health and aids in the prevention
      and reduction of many diseases. In 2008, the U.S. Department of Health and Human
      Services (DHHS) issued the Physical Activity Guidelines for Americans to foster
      appropriate levels of physical activity at various ages of development. Despite
      these guidelines and the known benefit to being physically active; physical
      activity levels are significantly lower in Blacks, contributing to higher
      prevalence of poor health outcomes. Therefore, the purpose of this paper was to
      look at four national datasets [Youth Risk Behavior Survey (YRBS), Behavioral
      Risk Factor Surveillance System (BRFSS), The National Health and Nutrition
      Examination Survey (NHANES), and National Health Interview Survey (NHIS)] to
      identify any patterns and trends that could be used to improve physical activity
      behavior within this population. These national datasets were used to estimate
      the proportion of Black adults and youth meeting national physical activity
      recommendations overall-stratified by age, gender and other demographic
      characteristics, to help identify patterns. The proportion of Black youth
      reporting regular physical activity ranged from 33% to 52%; and of Black adults,
      27% to 52%. Physical activity was highest among men, younger age groups, highest
      education and income groups, and those who were employed or married. Trends were
      consistent across surveys. Among Black youth, physical activity decline with
      increasing grade level, and improvements over the past 10 years have been
      minimal. The percentage of Black adults achieving physical activity guidelines
      has improved slightly over the last ten years, but physical activity
      participation is still low and continues to decline with age. Trends identified
      from examining these national datasets can be used to inform development of
      physical activity interventions aimed at promoting and maintaining regular
      physical activity behavior among high risk subgroups across the life span.

PMID- 30094278
TI  - A survey of Greek women's satisfaction of postnatal care.
AB  - Background: The research described in this paper is a cross-sectional study which
      surveys women who delivered their babies in a regional hospital in Greece to
      investigate their satisfaction with their postnatal care. This is the first
      published study which measures satisfaction of postnatal services in Greece. The
      aim of this study is to determine which factors most influence postnatal
      satisfaction, which areas are lacking and therefore identify specific areas which
      should be targeted to improve the performance of health services. Methods: A
      cross sectional, quantitative study of 300 women who gave birth in a regional
      Greek hospital between January 2015 and July 2017 were surveyed 40 days after
      birth using a self-administered questionnaire. The questionnaire contained
      sociodemographic and clinical characteristic questions and a selection of
      questions from the WOMen's views of Birth Postnatal Satisfaction Questionnaire
      (WOMBPNSQ). Results: This study found that the dimensions with the higher
      satisfaction scores were "Professional support" and "Continuity". The lower
      satisfaction scores were for the dimensions "Woman's health", "Contraceptive
      advice" and "Social support" indicating that these are areas for improvement. The
      three dimensions most correlated with general satisfaction were "Time with
      woman", "Feeding baby" and "Professional support". Conclusions: This study
      highlights the important role of health professionals showing that they can
      enhance postnatal satisfaction by spending time with the women, giving guidance
      on the care of the newborn and baby feeding. Focusing on improving these areas is
      expected to enhance the quality of postnatal care.

PMID- 30094279
TI  - Promoting aging migrants' capabilities: A randomized controlled trial concerning
      activities of daily living and self-rated health.
AB  - The aim was to evaluate the 6-month and 1-year effects of a person-centered group
      based health-promoting intervention on independence in daily activities and self
      rated health. The study was an RCT with follow-ups at 6 months and 1 year. A
      total of 131 independent living people (70+) who have migrated to Sweden from
      Finland or Western Balkan region were included. Participants were independent in
      activities of daily living and cognitively intact. They were randomized to an
      intervention group receiving four weekly group-meetings and a follow-up home
      visit, or a control group (no intervention). An overall chi-squared test was
      performed and the odds ratio calculated. A high proportion of the participants
      maintained independence in activities of daily living and improved or maintained
      self-rated health. However, no significant differences were found between the
      groups. The result indicates that the intervention was offered too early in the
      aging process to be able to detect effects. Methodological challenges were met
      during both the recruitment and implementation phases. In response to lessons
      learned, a multicenter design is recommended for future research in order to
      strengthen the findings. Furthermore, this study has contributed with experiences
      on both opportunities and challenges in terms of research with and about older
      people aging in the context of migration, as is discussed.

PMID- 30094280
TI  - Community pharmacists' attitudes towards patient leaflets: Exploring perceptions
      underlying an electronic local production of tailored written information.
AB  - Introduction: Low health literacy in Portugal, revealed by limited patients'
      knowledge of their medication, may be improved by written information that is
      individually tailored for each patient. Tailored content can be produced through
      computer software and delivered by community pharmacies to patients. Objective:
      To assess community pharmacists' real-life management, usage and perceived
      utility of software developed to produce individually tailored patient leaflets
      at community pharmacies. Methods: The software contained five different
      pharmacist-selected clinical information fields which allows for the adjustment
      of information to each patient's information needs. Using an exploratory study
      design, community pharmacists' perceptions were purposively selected and
      qualitatively assessed. Interviews were recorded, transcribed verbatim and
      iteratively coded using a thematic approach outlined by attitudinal theory.
      Results: Eight participants took part in the study. Emerging codes led to the
      construction of two main themes: Current PLs usage in Portuguese community
      pharmacy; and Tailored PLs usage in Portuguese community pharmacy. Pharmacists
      exhibited a generally positive attitude concerning the relevance and use of
      patient leaflets to address individual patient's information needs, including an
      improvement in health literacy. The model was considered effective, functional,
      satisfying and user-friendly. Conclusion: Although additional studies are needed,
      the introduction of a leaflet-tailoring software in Portuguese community
      pharmacies seems to be feasible as an additional resource to improve the quality
      of patient information and counselling. The next research steps should address
      the impact on patients' medicines-related information, including the level to
      which patients are able to correctly interpret the information and to adjust
      accordingly their health behaviours. Practice implications: The software fits
      present community pharmacy practice and routines, bringing advantages to
      pharmacists' willingness to deliver meaningful written information to patients,
      thus contributing to improved patient health literacy.

PMID- 30094281
TI  - Assessing the Status Quo of EHR Accessibility, Usability, and Knowledge
      Dissemination.
AB  - Aim: This study was performed to better characterize accessibility to electronic
      health records (EHRs) among informatics professionals in various roles, settings,
      and organizations across the United States and internationally. Background: The
      EHR landscape has evolved significantly in recent years, though challenges remain
      in key areas such as usability. While patient access to electronic health
      information has gained more attention, levels of access among informatics
      professionals, including those conducting usability research, have not been well
      described in the literature. Ironically, many informatics professionals whose aim
      is to improve EHR design have restrictions on EHR access or publication, which
      interfere with broad dissemination of findings in areas of usability research.
      Methods: To quantify the limitations on EHR access and publication rights, we
      conducted a survey of informatics professionals from a broad spectrum of roles
      including practicing clinicians, researchers, administrators, and members of
      industry. Results were analyzed and levels of EHR access were stratified by role,
      organizational affiliation, geographic region, EHR type, and restrictions with
      regard to publishing results of usability testing, including screenshots.
      Results: 126 respondents completed the survey, representing all major geographic
      regions in the United States. 71.5 percent of participants reported some level of
      EHR access, while 13 percent reported no access whatsoever. Rates of no-access
      were higher among faculty members and researchers (19 percent). Among faculty
      members and researchers, 72 percent could access the EHR for usability and/or
      research purposes, but, of those, fewer than 1 in 3 could freely publish
      screenshots with results of usability testing and half could not publish such
      data at all. Across users from all roles, only 21 percent reported the ability to
      publish screenshots freely without restrictions. Conclusions: This study offers
      insight into current patterns of EHR accessibility among informatics
      professionals, highlighting restrictions that limit dissemination of usability
      research and testing. Further conversations and shared responsibility among the
      various stakeholders in industry, government, health care organizations, and
      informatics professionals are vital to continued EHR optimization.

PMID- 30094282
TI  - Measuring the Delivery of Complex Interventions through Electronic Medical
      Records: Challenges and Lessons Learned.
AB  - Background: Health services and implementation researchers often seek to capture
      the implementation process of complex interventions yet explicit guidance on how
      to capture this process is limited. Medical record review is a commonly used
      methodology, especially when used as a proxy for provider behavior, with
      recognized benefits and limitations. The purpose of this study was to test the
      feasibility of chart review to measure implementation and offer recommendations
      for future researchers using this method to capture the implementation process.
      Methods: Grounded in qualitative research methods, we measured the implementation
      of a transitional care intervention for older adults with dementia being
      discharged from the hospital. We adapted the operationalization of the
      intervention's components to suit chart review methods, sought input from
      hospital providers before and after data collection, and assessed the agreement
      between the results of our chart review and provider-report. Findings: We believe
      chart review can be used effectively as a method for capturing the implementation
      process and provide future researchers with a list of recommendations based on
      our experience including understanding the nuance between data extraction versus
      data abstraction, allowing for large amounts of data not pre-specified in the
      data collection instrument to be collected, and purposefully and iteratively
      engaging the providers who are entering data into the chart. Major Themes:
      Measuring the implementation of complex interventions is a cornerstone in health
      services research and with the relative convenience and low costs of using chart
      data, we believe with more use and refinement this methodology could emerge as a
      valuable and widely used method in the field.

PMID- 30094283
TI  - A Query Workflow Design to Perform Automatable Distributed Regression Analysis in
      Large Distributed Data Networks.
AB  - Introduction: Patient privacy and data security concerns often limit the
      feasibility of pooling patient-level data from multiple sources for analysis.
      Distributed data networks (DDNs) that employ privacy-protecting analytical
      methods, such as distributed regression analysis (DRA), can mitigate these
      concerns. However, DRA is not routinely implemented in large DDNs. Objective: We
      describe the design and implementation of a process framework and query workflow
      that allow automatable DRA in real-world DDNs that use PopMedNetTM, an open
      source distributed networking software platform. Methods: We surveyed and
      catalogued existing hardware and software configurations at all data partners in
      the Sentinel System, a PopMedNet-driven DDN. Key guiding principles for the
      design included minimal disruptions to the current PopMedNet query workflow and
      minimal modifications to data partners' hardware configurations and software
      requirements. Results: We developed and implemented a three-step process
      framework and PopMedNet query workflow that enables automatable DRA: 1)
      assembling a de-identified patient-level dataset at each data partner, 2)
      distributing a DRA package to data partners for local iterative analysis, and 3)
      iteratively transferring intermediate files between data partners and analysis
      center. The DRA query workflow is agnostic to statistical software, accommodates
      different regression models, and allows different levels of user-specified
      automation. Discussion: The process framework can be generalized to and the query
      workflow can be adopted by other PopMedNet-based DDNs. Conclusion: DRA has great
      potential to change the paradigm of data analysis in DDNs. Successful
      implementation of DRA in Sentinel will facilitate adoption of the analytic
      approach in other DDNs.

PMID- 30094284
TI  - The Imperative for Patient-Centered Clinical Decision Support.
AB  - This commentary introduces the Patient-Centered Clinical Decision Support (PCCDS)
      Learning Network, which is collaborating with AcademyHealth to publish "Better
      Decisions Together" as part of eGEMs. Patient-centered clinical decision support
      (CDS) is an important vehicle to address broad issues in the U.S. health care
      system regarding quality and safety while also achieving better outcomes and
      better patient and provider satisfaction. Defined as CDS that supports individual
      patients and their care givers and/or care teams in health-related decisions and
      actions, PCCDS is an important step forward in advancing endeavors to move
      patient-centered care forward. The PCCDS Learning Network has developed a
      framework, referred to as the Analytic Framework for Action (AFA), to organize
      thinking and activities around PCCDS. A wide array of activities the PCCDS
      Learning Network is engaging in to inform and connect stakeholders is discussed.

PMID- 30094285
TI  - Architecture and Implementation of a Clinical Research Data Warehouse for
      Prostate Cancer.
AB  - Background: Electronic health record (EHR) based research in oncology can be
      limited by missing data and a lack of structured data elements. Clinical research
      data warehouses for specific cancer types can enable the creation of more robust
      research cohorts. Methods: We linked data from the Stanford University EHR with
      the Stanford Cancer Institute Research Database (SCIRDB) and the California
      Cancer Registry (CCR) to create a research data warehouse for prostate cancer.
      The database was supplemented with information from clinical trials, natural
      language processing of clinical notes and surveys on patient-reported outcomes.
      Results: 11,898 unique prostate cancer patients were identified in the Stanford
      EHR, of which 3,936 were matched to the Stanford cancer registry and 6153 in the
      CCR. 7158 patients with EHR data and at least one of SCIRDB and CCR data were
      initially included in the warehouse. Conclusions: A disease-specific clinical
      research data warehouse combining multiple data sources can facilitate secondary
      data use and enhance observational research in oncology.

PMID- 30094286
TI  - Generation and Implementation of a Patient-Centered and Patient-Facing Genomic
      Test Report in the EHR.
AB  - Context: Communication of genetic laboratory results to patients and providers is
      impeded by the complexity of results and reports. This can lead to
      misinterpretation of results, causing inappropriate care. Patients often do not
      receive a copy of the report leading to possible miscommunication. To address
      these problems, we conducted patient-centered research to inform design of
      interpretive reports. Here we describe the development and deployment of a
      specific patient-centered clinical decision support (CDS) tool, a multi-use
      patient-centered genomic test report (PGR) that interfaces with an electronic
      health record (EHR). Implementation Process: A PGR with a companion provider
      report was configured for implementation within the EHR using locally developed
      software (COMPASSTM) to manage secure data exchange and access. Findings: We
      conducted semi-structured interviews with patients, family members, and
      clinicians that showed they sought clear information addressing findings, family
      implications, resources, prognosis and next steps relative to the genomic result.
      Providers requested access to applicable, available clinical guidelines. Initial
      results indicated patients and providers found the PGR contained helpful,
      valuable information and would provide a basis for result-related conversation
      between patients, providers and family. Major Themes: Direct patient involvement
      in the design and development of a PGR identified format and presentation
      preferences, and delivery of relevant information to patients and providers,
      prompting the creation of a CDS tool. Conclusions: Research and development of
      patient-centered CDS tools designed to support improved patient outcomes, are
      enhanced by early and substantial engagement of patients in contributing to all
      phases of tool design and development.

PMID- 30094287
TI  - Methods for Patient-Centered Interface Design of Test Result Display in Online
      Portals.
AB  - Objectives: Patients have unique information needs to help them interpret and
      make decisions about laboratory test results they receive on web-based portals.
      However, current portals are not designed in a patient-centered way and little is
      known on how best to harness patients' information needs to inform user-centered
      interface design of portals. We designed a patient-facing laboratory test result
      interface prototype based on requirement elicitation research and used a mixed
      methods approach to evaluate this interface. Methods: After designing an initial
      test result display prototype, we used multiple evaluation methods, including
      focus group review sessions, expert consultation, and user testing, to make
      iterative design changes. For the user testing component, we recruited 14 patient
      users to collect and analyze three types of data: comments made during testing
      sessions, responses to post-session questionnaires, and system usability scores.
      Results: Our initial patient-centered interface design included visual ranges of
      laboratory values, nontechnical descriptions of the test and result, and access
      to features to help patients interpret and make decisions about their results.
      Findings from our evaluation resulted in 6 design iterations of the interface.
      Results from user testing indicate that the later versions of the interface
      fulfilled patient's information needs, were perceived as usable, and provided
      access to information and techniques that facilitated patient's ability to derive
      meaning from each test result. Conclusions: Requirement elicitation studies can
      inform the design of a patient-facing test result interface, but considerable
      user-centered design efforts are necessary to create an interface that patients
      find useful. To promote patient engagement, health information technology
      designers and developers can use similar approaches to enhance user-centered
      software design in patient portals.

PMID- 30094288
TI  - Delivering Patient Data to Patients Themselves.
AB  - Physicians need nearly a decade of training to understand complex patient data
      such as laboratory tests and genomic data. How can these data possibly be
      delivered to patients in ways that they can understand and use?

PMID- 30094289
TI  - Understanding the Impact of Variations in Measurement Period Reporting for
      Electronic Clinical Quality Measures.
AB  - Objective: To understand the impact of varying measurement period on the
      calculation of electronic Clinical Quality Measures (eCQMs). Background: eCQMs
      have increased in importance in value-based programs, but accurate and timely
      measurement has been slow. This has required flexibility in key measure
      characteristics, including measurement period, the timeframe the measurement
      covers. The effects of variable measurement periods on accuracy and variability
      are not clear. Methods: 209 practices were asked to extract and submit four eCQMs
      from their Electronic Health Records on a quarterly basis using a 12-month
      measurement period. Quarterly submissions were collected via REDCap. The
      measurement periods of the survey data were categorized into non-standard (3, 6,
      9 months and other) and standard periods (12 months). For comparison, patient
      level data from three clinics were collected and calculated in an eCQM registry
      to measure the impact of varying measurement periods. We assessed the central
      tendency, shape of the distributions, and variability across the four measures.
      Analysis of variance (ANOVA) was conducted to analyze the differences among
      standard and non-standard measurement period means, and variation among these
      groups. Results: Of 209 practices, 191 (91 percent) submitted data over three
      quarters. Of the 546 total submissions, 173 had non-standard measurement periods.
      Differences between measures with standard versus non-standard periods ranged
      from -3.3 percent to 14.2 percent between clinics (p < .05 for 3 of 4), using the
      patient-level data yielded deltas of -1.6 percent to 0.6 percent when comparing
      non-standard and standard periods. Conclusion: Variations in measurement periods
      were associated with variation in performance between clinics for 3 of the 4
      eCQMs, but did not have significant differences when calculated within clinics.
      Variations from standard measurement periods may reflect poor data quality and
      accuracy.

PMID- 30094290
TI  - Measuring Early Hearing Detection and Intervention (EHDI) Quality across the
      Continuum of Care.
AB  - Improving quality measurement while reducing costs helps public health programs
      identify and better support critical aspects of the care and services delivered
      to the patients they serve. This is true for state-based early hearing detection
      and intervention (EHDI) programs as they strive to develop robust clinical
      quality measures to help track the quality of hearing health services provided
      during the EHDI processes. Leveraging today's electronic health records and
      public health surveillance system functionalities, state reporting requirements
      facilitate and yield efficient collection and analysis of data for quality
      measurement. In this study, we tested three EHDI quality measures endorsed by the
      National Quality Forum using a retrospective sample of more than 1,100,000
      newborns from 3 states using electronic health data available in the state EHDI
      Information Systems (EHDI-IS). The results of the analysis reported herein from a
      large multi-state cohort provide a "real life" benchmark for future quality
      improvement projects and of where EHDI stands today. Reflecting on these
      findings, suggestions are posed for enhancing the EHDI quality measures in future
      updates.

PMID- 30094291
TI  - Using Immediate Response Technology to Gather Electronic Health Data and Promote
      Telemental Health Among Youth.
AB  - Introduction: A sizeable number of youth are currently struggling with anxiety,
      depression, and suicidal thoughts, yet many will not receive treatment. We sought
      to better understand if immediate response technology (IRT) could be used to
      gather mental health care data and educate youth on telemental health (TMH)
      resources. Methods: Using an IRT imbedded within an interactive, media-rich
      school-based presentation, we gathered mental health history and preferences for
      TMH resources from 2,789 adolescents with a wide range of demographic and
      psychological characteristics. Results: More than 80 percent of adolescents
      satisfied inclusion criteria for survey completion, and responses were
      statistically comparable across four diverse high school settings. Using Chi
      squared analyses, we found that less than 10 percent of adolescents, especially
      girls and those with high depression/anxiety scores, had previously used TMH
      resources. After interacting with the IRT, many more (29 percent to 43 percent)
      expressed willingness to use these resources. Discussion: The IRT system was
      effective in gathering mental electronic health data, delivering targeted mental
      health education, and promoting positive attitudes towards TMH among adolescents.
      Conclusions: IRTs and other non-formalized technologies should be explored as
      cost-effective, easy-to-implement resources for electronic health data gathering
      and health care education.

PMID- 30094293
TI  - Infectious Complications of Multiple Sclerosis Therapies: Implications for
      Screening, Prophylaxis, and Management.
AB  - Multiple sclerosis therapies include interferons, glatiramer, and multiple
      immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs
      requires understanding their mechanisms of action and analyzing interventional
      studies and postmarketing observational data. Though identical immunosuppressive
      therapies are sometimes used in non-neurologic conditions, infectious risks may
      differ in this population. Screening for and treatment of latent tuberculosis
      (TB) infection should be prioritized for patients receiving alemtuzumab;
      ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B
      virus (HBV) reactivation can be devastating for patients treated with ocrelizumab
      and alemtuzumab, whereas the small molecule oral agents do not likely pose
      substantial risk of HBV. Progressive multifocal leukoencephalopathy is a
      particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and
      fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual
      opportunistic infections have been described. Vaccination is an important tool in
      preventing infections, though vaccine timing and contraindications can be
      complex.

PMID- 30094292
TI  - Detrimental Outcomes of Unmasking Cryptococcal Meningitis With Recent ART
      Initiation.
AB  - Background: Increased antiretroviral therapy (ART) availability has been
      associated with more patients developing cryptococcosis after ART initiation.
      Despite this changing epidemiology, data regarding cryptococcal meningitis in
      those already receiving ART are limited. We compared clinical presentations and
      outcomes among ART-naive and ART-experienced Ugandans. Methods: We prospectively
      enrolled 605 HIV-infected persons with first-episode cryptococcal meningitis from
      August 2013 to May 2017 who received amphotericin-based combination therapy. We
      classified participants by ART status and ART duration and compared groups for 2
      week survival. Results: Overall, 46% (281/605) of participants were receiving ART
      at presentation. Compared with those not receiving ART, those receiving ART had
      higher CD4 counts (P < .001) and lower cerebrospinal fluid fungal burdens (P <
      .001). Of those receiving ART, 56% (156/281) initiated ART within 6 months, and
      18% (51/281) initiated ART within 14 days. Two-week mortality did not differ by
      ART status (27% in both ART-naive and ART-experienced%; P > .99). However, 47%
      (24/51) of those receiving ART for <=14 days died within 2 weeks, compared with
      19% (20/105) of those receiving ART for 15-182 days and 26% (32/125) of those
      receiving ART for >6 months (P < .001). Among persons receiving ART for >6
      months, 87% had HIV viral loads >1000 copies/mL. Conclusions: Cryptococcosis
      after ART initiation is common in Africa. Patients initiating ART who unmask
      cryptococcal meningitis are at a high risk of death. Immune recovery in the
      setting of central nervous system infection is detrimental, and management of
      this population requires further study. Implementing pre-ART cryptococcal antigen
      screening is urgently needed to prevent cryptococcal meningitis after ART
      initiation.

PMID- 30094295
TI  - Special Section Guest Editorial: Medical Image Perceptions and Observer
      Performance.
AB  - This guest editorial introduces the special section on Medical Image Perceptions
      and Observer Performance.

PMID- 30094296
TI  - Is there a role for perfusion imaging in assessing treatment response following
      ablative therapy of small renal masses-A systematic review.
AB  - Aims: Ablation therapies are an innovative nephron-sparing alternative to radical
      nephrectomy for early stage renal cancers, although determination of treatment
      success is challenging. We aimed to undertake a systematic review of the
      literature to determine whether assessment of tumour perfusion may improve
      response assessment or alter clinical management when compared to standard
      imaging. Material and Methods: Two radiologists performed independent primary
      literature searches for perfusion imaging in response assessment following
      ablative therapies (radiofrequency ablation and cryotherapy) focused on renal
      tumours. Results: 5 of 795 articles were eligible, totaling 110 patients. The
      study designs were heterogeneous with different imaging techniques, perfusion
      calculations, reference standard and follow-up periods. All studies found lower
      perfusion following treatment, with a return of 'high grade' perfusion in the
      7/110 patients with residual or recurrent tumour. One study found perfusion
      curves were different between successfully ablated regions and residual tumour.
      Conclusions: Studies were limited by small sample size and heterogeneous
      methodology. No studies have investigated the impact of perfusion imaging on
      management. This review highlights the current lack of evidence for perfusion
      imaging in response assessment following renal ablation, however it suggests that
      there may be a future role. Further prospective research is required to address
      this.

PMID- 30094294
TI  - An Introduction to the Analysis of Single-Cell RNA-Sequencing Data.
AB  - The recent development of single-cell RNA sequencing has deepened our
      understanding of the cell as a functional unit, providing new insights based on
      gene expression profiles of hundreds to hundreds of thousands of individual
      cells, and revealing new populations of cells with distinct gene expression
      profiles previously hidden within analyses of gene expression performed on bulk
      cell populations. However, appropriate analysis and utilization of the massive
      amounts of data generated from single-cell RNA sequencing experiments are
      challenging and require an understanding of the experimental and computational
      pathways taken between preparation of input cells and output of interpretable
      data. In this review, we will discuss the basic principles of these new
      technologies, focusing on concepts important in the analysis of single-cell RNA
      sequencing data. Specifically, we summarize approaches to quality-control
      measures for determination of which single cells to include for further
      examination, methods of data normalization and scaling to overcome the relatively
      inefficient capture rate of mRNA from each cell, and clustering and visualization
      algorithms used for dimensional reduction of the data to a two-dimensional plot.

PMID- 30094300
TI  - Circinate oral and genital mucositis.

PMID- 30094299
TI  - Genital ulcers in an immunocompromised man.

PMID- 30094297
TI  - Characteristics of bone strength and metabolism in type 2 diabetic model Tsumura,
      Suzuki, Obese Diabetes mice.
AB  - Objective: Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized
      by hyperglycemia, hyperinsulinemia, and complications such as obesity and
      osteoporosis. The Tsumura, Suzuki, Obese Diabetes (TSOD) mouse is an animal model
      of spontaneous obese T2DM. However, bone metabolism in TSOD mice is yet to be
      investigated. The objective of the present study was to investigate the effects
      of T2DM on bone mass, metabolism, microstructure, and strength in TSOD mice.
      Methods: We determined the following parameters in TSOD mice and Tsumura, Suzuki,
      Non-obesity (TSNO) mice (as controls): serum glucose levels; serum insulin
      levels; bone mass; bone microstructure; bone metabolic markers; and bone
      strength. We also performed the oral glucose tolerance test and examined
      histological sections of the femur. We compared these data between both groups at
      pre-diabetic (10 weeks) and established (20 weeks) diabetic conditions. Results:
      Bone strength, such as extrinsic mechanical properties, increased with age in the
      TSOD mice and intrinsic material properties decreased at both 10 weeks and 20
      weeks. Bone resorption marker levels in TSOD mice were significantly higher than
      those in the control mice at both ages, but there was no significant difference
      in bone formation markers between the groups. Bone mass in TSOD mice was lower
      than that in controls at both ages. The trabecular bone volume at the femoral
      greater trochanter increased with age in the TSOD mice. The femoral mid-diaphysis
      in TSOD mice was more slender and thicker than that in TSNO mice at both ages.
      Conclusions: Bone mass of the femur was lower in TSOD mice than in TSNO mice
      because hyperinsulinemia during pre-diabetic and established diabetic conditions
      enhanced bone resorption due to high bone turnover. In addition, our data suggest
      that the bone mass of the femur was significantly reduced as a result of chronic
      hyperglycemia during established diabetic conditions in TSOD mice. We suggest
      that bone strength in the femur deteriorated due to the reduction of bone mass
      and because the femoral mid-diaphysis was more slender in TSOD mice.

PMID- 30094298
TI  - Polyethylene particles inserted over calvarium induce cancellous bone loss in
      femur in female mice.
AB  - Focal bone resorption (osteolysis) induced by wear particles contributes to long
      term orthopedic joint failure. However, the impact of focal osteolysis on remote
      skeletal sites has received less attention. The goal of this study was to
      determine the effects of polyethylene particles placed over calvaria on
      representative axial and appendicular skeletal sites in female mice. Because
      recent work has identified housing temperature as an important biological
      variable in mice, response to particle treatment was measured in animals housed
      at room (22  degrees C) and thermoneutral (32  degrees C) temperature. Osteolysis
      was evident in skeletal tissue adjacent to particle insertion. In addition,
      cancellous bone loss was observed in distal femur metaphysis. The bone loss was
      associated with lower osteoblast-lined perimeter and lower mineralizing perimeter
      in distal femur, lower osteocalcin gene expression in tibia, and lower serum
      osteocalcin, suggesting the response was due, at least in part, to reduced bone
      formation. Mild cold stress induced by sub-thermoneutral housing resulted in
      cancellous bone loss in distal femur and lumbar vertebra but did not influence
      skeletal response to particles. In summary, the results indicate that focal
      inflammation induced by polyethylene particles has the potential to result in
      systemic bone loss. This is significant because bone loss is a risk factor for
      fracture.

PMID- 30094301
TI  - Papules developing in an old tattoo.

PMID- 30094302
TI  - Correction of cicatricial and involutional lower eyelid ectropion with hyaluronic
      acid.

PMID- 30094303
TI  - Multiple granuloma annulare lesions presenting simultaneously with herpes zoster
      infection: Wolf's isotopic response.

PMID- 30094304
TI  - Linear basal cell carcinoma of the lower eyelid: Reconstruction with a
      musculocutaneous transposition flap.

PMID- 30094305
TI  - Programmed cell death protein-1 inhibitor-induced granuloma annulare and
      hypertrophic lichen planus masquerading as squamous cell carcinoma.

PMID- 30094306
TI  - Brachioradial pruritus treated with computed tomography-guided cervical nerve
      root block: A case series.

PMID- 30094307
TI  - Acute localized exanthematous pustulosis (ALEP) caused by lamotrigine.

PMID- 30094308
TI  - Two cases of treatment with aromatase inhibitors and development of miliary
      osteoma cutis-Is there an association?

PMID- 30094309
TI  - Peripheral T-cell lymphoma, not otherwise specified, presenting with generalized
      ulcerated plaques and hypereosinophilia.

PMID- 30094310
TI  - Methods of phenotypic identification of non-tuberculous mycobacteria.
AB  - Non-tuberculous mycobacteria (NTM) are composed of mycobacterial species other
      than the Mycobacterium tuberculosis complex. Initially thought to be mere
      contaminants when isolated from clinical specimens, literature is increasing by
      the day showing NTM as proven pathogens. Due to the difference in antimicrobial
      susceptibility of different species, it becomes imperative for the microbiology
      laboratory to identify them to the species level. Molecular methods are available
      for rapid and accurate identification, but in a resource limited nation,
      phenotypic methods, albeit time consuming, are of paramount importance. By means
      of this article, the authors intend provide a concise summary of the basic
      biochemical reactions which can be done to identify most commonly isolated NTM.

PMID- 30094311
TI  - Imaging and cancer of the cervix in low- and middle-income countries.
AB  - Cervix cancer is the fourth most common cancer globally but the second most
      cancer in women in resource-limited countries. It has remained a clinically
      staged neoplasm as per the International Federation of Gynecology and Obstetrics
      staging classification. As the imaging machines are becoming more available
      worldwide, the resource-stratified guidelines recommended the inclusion of
      imaging whenever possible to guide treatment planning. In this report, the
      utility of imaging in low- and middle-income countries for diagnosis and
      treatment of cancer of the cervix will be reviewed.

PMID- 30094312
TI  - Simultaneous resection of endometrial cancer and high-level paraaortic
      paraganglioma using retroperitoneoscopic surgery.
AB  - *Paraganglioma is sometimes suspected as lymph node metastasis or lymph node
      recurrence of various malignant tumors.*Retroperitoneoscopic surgery is a valid
      approach to treat the tumor, located above the renal vein.*Resection using
      retroperitoneoscopic surgery without catecholamine-related complications is
      possible.

PMID- 30094313
TI  - Two types of small cell carcinoma of the ovary: Two typical case reports.
AB  - *This report shows very rare cases of small cell carcinoma of the ovary,
      hypercalcemic type and pulmonary type.*Their chemo sensitivity is quite
      different. These two cases followed opposite clinical courses.*The first case
      (SCOHT) progressed rapidly, and showed resistance to chemotherapy and
      radiotherapy.*The second case (SCOPT) showed sensitivity to chemotherapy and
      radiotherapy although recurrence was repeated.

PMID- 30094314
TI  - The best of intentions: Prenatal breastfeeding intentions and infant health.
AB  - Health organizations recommend that mothers exclusively breastfeed infants for
      the first six months of life. The current study contributes to a growing body of
      research that examines whether the purported benefits of breastfeeding are
      causal. We systematically evaluated the role of an expectant mother's prenatal
      breastfeeding intentions, which reflect not only demographic characteristics, but
      also knowledge, attitudes, and social norms about infant feeding, and therefore
      serve as a proxy for positive maternal selection into breastfeeding. We used the
      Infant Feeding Practices Study (IFPS) II (n = 1008) to examine a heretofore
      overlooked group of mothers-those who intended to breastfeed but did not actually
      breastfeed. Results suggest that mothers who intended to breastfeed had infants
      with fewer ear infections and respiratory syncytial viruses, and used fewer
      antibiotics in the first year of life compared to infants whose mothers did not
      intend to breastfeed, irrespective of whether they actually breastfed. Because
      breastfeeding intention is a confounding characteristic that proxies for positive
      maternal selection and does not represent a causal mechanism for infant health,
      we further examined how mothers who intended to breastfeed differed from mothers
      who did not intend to breastfeed. Results suggest that mothers who intended to
      breastfeed had more knowledge about potential food contaminants and consulted
      more sources of information about nutrition and diet than mothers who did not
      intend to breastfeed. Taken together, our results underscore the need for new
      policy interventions aimed at improving infant health.

PMID- 30094315
TI  - Mind the gap: Temporal trends in inequalities in infant and child mortality in
      India (1992-2016).
AB  - *Temporal trends in inequalities in infant and child mortality over two and half
      decades in India.*Relative change in inequalities in child mortality over survey
      periods.*Scatter plots to identify states with largest inequalities among wealth
      index groups.*Concentration Index by various background characteristics and
      decomposition analysis to identify factors contributing in inequality in infant
      mortality between richest and poorest groups.*Gap between the poorest and richest
      groups has narrowed in most states in India in recent years.

PMID- 30094316
TI  - Weighed down by discriminatory policing: Perceived unfair treatment and black
      white disparities in waist circumference.
AB  - Police maltreatment, whether experienced personally or indirectly through one's
      family or friends, represents a potentially harmful stressor, particularly for
      minority populations. We address this issue by investigating: (1) how waist
      circumference (WC) varies by personal and vicarious exposure to unfair treatment
      by police (UTBP); and (2) to what extent exposure to UTBP explains the black
      white disparity in WC. We employed data collected from a community-based sample
      of black (n = 601) and white (n = 608) adults living in Nashville-Davidson county
      Tennessee to address these questions. Results from our final linear regression
      model showed that those who reported vicarious UTBP had WCs that were
      approximately 2 in. greater than those who did not (b = 2.03; p = 0.003). While
      personal UTBP was not linked to higher WC, a post-hoc analysis suggested that our
      ability to detect an association was complicated by selection. Binary mediation
      analysis revealed that differential exposure to vicarious UTBP accounted for
      approximately 12% of the black-white WC disparity among women. We found no black
      white differences in WC among men. The association between vicarious UTBP and WC
      did not vary by age, race, or gender. Overall, our findings point toward the role
      of discriminatory policing as a potential upstream contributor to racial
      disparities in health.

PMID- 30094317
TI  - Decomposition of age- and cause-specific adult mortality contributions to the
      gender gap in life expectancy from census and survey data in Zambia.
AB  - In the context of high adult mortality and an immense impact on the health burden
      of Zambia, a decomposition analysis of age- and cause-specific mortality in age
      group 15-59 was performed to determine the contributions to the gap in life
      expectancy at birth between males and females. Previous studies on decomposition
      have examined income groups, ethnicity, and regional differences' contributions
      to gaps in life expectancy, but not the adult mortality age group 15-59. These
      studies focus on developed countries and few on developing countries. Arriaga's
      decomposition method was applied to 2010 census and 2010-2012 sample vital
      registration with verbal autopsy survey (SAVVY) data to decompose contributions
      of age- and cause-specific adult mortality to the gap in life expectancy at birth
      between males and females. The decomposition analysis revealed that mortality was
      higher among males than females and concentrated in age groups 20-49. Age- and
      cause-specific adult mortality contributed positively, 50% of the years to the
      gap in life expectancy at birth between males and females. Major cause-specific
      mortality contributors to the gap in life expectancy were infectious and
      parasitic diseases (1.17 years, 26.3%), accidents and injuries (0.54 years,
      12.2%), suicide and violence (0.30 years, 6.8%). Female HIV mortality offset male
      mortality. Neoplasms deaths among females contributed negatively to the gap in
      life expectancy (-0.22 years, -5.4%). Accidents, injuries, suicide, and violence
      are emerging major causes of death in age group 20-49 in Zambia which health
      policy and programmes should target.

PMID- 30094318
TI  - Perceived neighborhood disorder, racial-ethnic discrimination and leading risk
      factors for chronic disease among women: California Behavioral Risk Factor
      Surveillance System, 2013.
AB  - Social environmental factors are theoretically identified as influential drivers
      of health behaviors - tobacco smoking, alcohol consumption, and physical activity
      - related to chronic disease disparities. Empirical studies investigating
      relationships involving social environmental factors have found that either
      greater interpersonal racial-ethnic discrimination or perceived neighborhood
      disorder were associated with adverse health behaviors, with potentially larger
      effects among women. We simultaneously tested whether measures of perceived
      racial-ethnic discrimination and perceived neighborhood disorder were associated
      with physical activity, alcohol consumption and tobacco smoking; lifestyle risk
      factors of major chronic disease among women. Data were from the 2013 California
      Behavioral Risk Factor Surveillance System. In addition to demographic and
      socioeconomic factors, women self-reported experiences with racial-ethnic
      discrimination and perception of neighborhood disorder (i.e., crime safety,
      traffic safety, and aesthetics/physical disorder). Survey-, and inverse
      probability of censoring-weighted regression models of each chronic disease risk
      factor were used to investigate associations involving racial-ethnic
      discrimination and neighborhood disorder, controlling for potential confounders.
      Perceiving racial-ethnic discrimination and greater neighborhood disorder were
      associated with a greater tobacco smoking prevalence. Experiences of racial
      ethnic discrimination were associated with greater alcohol consumption among
      African American and Latino women, but not White women. Similarly, African
      American women reporting experiences with racial-ethnic discrimination report
      engaging in physical activity about half as much time as women reporting no
      racial-ethnic discrimination. Increases in perceived neighborhood disorder were
      associated with increases in alcohol consumption. All associations with social
      environmental factors were adjusted for potential confounders and each other.
      Neighborhood disorder and racial-ethnic discrimination may be important,
      independent contributors to chronic disease risk through relationships with
      tobacco smoking, alcohol consumption, and physical activity.

PMID- 30094319
TI  - The rise and fall of mortality inequality in South Africa in the HIV era.
AB  - Post-apartheid South Africa has seen an unprecedented rise and fall of mortality
      in less than two decades as a result of the HIV/AIDS epidemic and the subsequent
      rollout of free antiretroviral therapy (ART). Since the incidence of both was not
      equal for rich and poor, it is likely to also have affected disparities in health
      and survival chances by income. We use large nationwide surveys for 2001, 2007
      and 2011 to obtain estimates of average income and mortality at the aggregate
      level of a municipality, and then to examine changes in mortality - and in
      inequality in mortality by income ? over time. Using concentration indices to
      measure health inequality, we demonstrate that both the mean mortality level and
      absolute inequality in mortality by income rose rapidly until 2006, and declined
      again sharply since the rollout of free ART. Relative inequalities in mortality
      by income, however, remained fairly stable over the 2001-2011 period. The
      analysis of age-sex-specific mortality rates shows that it was in particular for
      adults aged 18-59 years that mortality and absolute inequality increased
      substantially between 2001 and 2006, followed by a rapid drop thereafter. These
      trends were far more pronounced for males than females. This means that the
      HIV/AIDS epidemic has taken a serious death toll, which was concentrated
      disproportionately among the poorest segments of the population and especially
      affected (older) males. While South Africa has been very successful in curbing
      the overall mortality trend since 2006, large disparities in survival prospects
      by income, race and gender continue to exist. Targeted efforts are required if it
      wants to further reduce the very unequal chances of living to old age for richer
      and poorer population groups of all ages.

PMID- 30094320
TI  - Wide educational disparities in young adult cardiovascular health.
AB  - Widening educational differences in overall health and recent stagnation in
      cardiovascular disease mortality rates highlight the critical need to describe
      and understand educational disparities in cardiovascular health (CVH) among U.S.
      young adults. We use two data sets representative of the U.S. population to
      examine educational disparities in CVH among young adults (24-34) coming of age
      in the 21st century: the National Health and Nutrition Examination Survey (2005
      2010; N= 689) and the National Longitudinal Study of Adolescent to Adult Health
      (2007-2008; N=11,200). We employ descriptive statistics and regression analysis.
      The results show that fewer than one in four young adults had good CVH (at least
      5 out of 7 ideal cardiovascular indicators). Young adults who had not attained a
      college degree demonstrate particularly disadvantaged CVH compared with their
      college-educated peers. Such educational disparities persist after accounting for
      a range of confounders, including individuals' genetic propensity to develop
      coronary artery disease. The results indicate that the CVH of today's young
      adults is troubling and especially compromised for individuals with lower levels
      of educational attainment. These results generate substantial concern about the
      future CVH of the US population, particularly for young adults with a low level
      of education.

PMID- 30094322
TI  - Intrinsic and instrumental perspectives to sanitation.
AB  - Public health interventions are often implemented because they are a means to an
      end. For example, improving population-level health outcomes is a key step
      towards improving social and economic outcomes, too. But what is often overlooked
      is the fact that a given public health intervention might be the end in itself.
      In other words, a given intervention might be worth investing in even if there
      are zero returns from investing in it. This intrinsic value, however, is often
      overlooked. In this commentary, we look specifically at sanitation, and why the
      development community should motivate sanitation interventions using an intrinsic
      value perspective. We also extend the conversation to why there needs to be a
      fundamental shift away from demand-side interventions to supply-side
      interventions. In doing so, we hope to offer a more equitable perspective to
      health and development.

PMID- 30094321
TI  - The association between women's sanitation experiences and mental health: A cross
      sectional study in Rural, Odisha India.
AB  - Emerging qualitative research suggests women's sanitation experiences may impact
      mental health. However, specific associations remain unclear. We aimed to
      determine if sanitation access and sanitation experiences were associated with
      mental health among women in rural Odisha, India. Using a cross-sectional design,
      we evaluated the association between sanitation access and sanitation experiences
      and selected mental health outcomes. Data were collected from 1347 randomly
      selected women across four life course stages in 60 rural communities (December
      2014-February 2015). Our four primary outcomes included: mental well-being, and
      symptoms of anxiety, depression, and distress. The primary exposures were (1)
      access to a functional latrine within the household compound and (2) sanitation
      insecurity (SI), evaluated using a seven domain measure assessing women's
      negative sanitation experiences and concerns. We used hierarchical linear
      modeling to determine associations between the exposures and mental health
      outcomes, adjusting for covariates (life stage, poverty, current health status,
      social support). Mean well-being scores were moderate and mean anxiety,
      depression, and distress scores were above a threshold indicating the potential
      presence of any of the three conditions. Access to a functional household latrine
      was associated with higher well-being scores, but not with anxiety, depression or
      distress. Women's SI domains were associated with all four outcomes: four domains
      were significantly associated with lower well-being scores, two were
      significantly associated with higher anxiety scores, three were significantly
      associated with higher depression scores, and three were significantly associated
      with higher distress scores, all independent of functional household latrine
      access. Women in rural Odisha, India may suffer assaults to their well-being and
      have higher symptoms of anxiety, depression, and distress when urinating and
      defecating, even if they have an available facility. These findings suggest that
      sanitation-related interventions should consider how to accommodate women's
      experiences beyond excreta management to comprehensively impact health.

PMID- 30094323
TI  - Drinking wine to "get high": The influence of awareness of the negative effects
      among young adults.
AB  - Introduction: In a group of university students, the current study investigated
      the relationship between drinking wine to get high and the awareness about its
      characteristics, composition, positive and negative effects on health. Methods:
      Through a web-based survey, 1685 students at the University of Siena completed a
      self-report questionnaire to assess consumption behaviours, knowledge about wine
      and the awareness about its effects. Results: Seventy-three percent reported
      drinking wine. Males were more frequently wine consumers (p = 0.037). Among the
      students who reported drinking, 69.3% engaged this habit during the weekend.
      Almost 12% reported drinking wine to get high. Drinking wine to get high
      correlated with the consideration of its consumption: using this beverage to get
      high was strongly associated with considering wine like other spirits (p =
      0.033). Conclusions: Older age, female gender, and considering wine as a part of
      the diet were found to be protective factors against wine drinking-to get high.
      In contrast with some literature, awareness of the negative effects correlated
      with higher propensity to use wine to get high. Potential interpretations and
      limitations are addressed.

PMID- 30094324
TI  - Long-term smoking cessation rates in elderly versus other adult smokers: A 3-year
      follow-up study in Taiwan.
AB  - Introduction: Smoking cessation improves life expectancy at any age. There is
      some evidence that elderly smokers have at least as good a chance of successfully
      stopping as other smokers but direct comparisons with long-term follow up are
      rare. This study aimed to compare success rates up to 3 years in smokers aged 65+
      versus other adult smokers with and without adjustment for a range of other
      smoker characteristics. Methods: This was a prospective study of 1065 smokers who
      attended a stop-smoking clinic in Taiwan. Participants (896 < 65 years, 169 65+
      years) were followed up by telephone 3, 6, 12 and 36 months after the initial
      quit date. Prolonged abstinence (abstinent at all follow-ups) and point
      prevalence abstinence (7 days prior to final follow up) were compared between
      'elderly' participants aged 65+ years versus 'non-elderly' participants aged <65
      years with and without adjustment for a range of baseline smoker characteristics
      (sex, educational level, previous quit attempts, cigarette dependence score). Non
      responders were considered to be smoking. Results: Prolonged 36-month abstinence
      rates were 20.1% (N = 34) and 15.3% (N = 137) in the elderly and non-elderly
      participants respectively (p = 0.137). Point prevalence 36-month abstinence rates
      were 37.3% (N = 63) and 26.5% (N = 237) in the elderly and non-elderly
      participants respectively (p = 0.005). The odds ratios comparing elderly versus
      non-elderly abstinence rates after adjustment for baseline variables were 1.17
      (95%CI = 0.75-1.83) and 1.52 (95%CI = 1.05-2.20) for prolonged abstinence and
      point prevalence abstinence respectively. Conclusions: Elderly smokers attending
      smoker clinics in Taiwan appear to be at least as likely to achieve long-term
      abstinence as other adult smokers.

PMID- 30094325
TI  - Access to information in school and the use of psychoactive substances in
      Brazilian students - A multilevel study.
AB  - Introduction: Use of tobacco, alcohol and other drugs can be considered a global
      health problem, which typically begins in adolescence. Unsupervised access to
      information may arouse the adolescent's interest and predispose the use of drugs.
      Methodology: This is a cross-sectional study using data from National School
      based Health Survey (PeNSE, 2012), with sample of 109,104 Brazilian students in
      42.717 schools. Outcomes were: self-reported use of alcohol, tobacco, and other
      drugs in the past 30 days. Main exposures were contextual and included: library
      and media resources availability, computer room and internet available at school.
      Data analysis included multilevel logistic regression. Results: Prevalence of
      alcohol use was 25.2% (IC95% 24.7-25.6), tobacco use was 5.3% (IC95% 5.1-5.5) and
      use of other drugs was 2.6% (IC95% 2.5-2.7). Multilevel analysis showed that
      recent use of alcohol and tobacco was associated to the presence of computer room
      and internet, while the use of other drugs presented an association with all
      media. Conclusion: Results indicate that supervision in access to information and
      communication resources may play a role on the prevention of alcohol, tobacco and
      other drugs use by students.

PMID- 30094326
TI  - Relationship between frailty and Alzheimer's disease biomarkers: A scoping
      review.
AB  - Introduction: Frailty and dementia appear to be closely linked, although
      mechanisms remain unclear. The objective was to conduct a scoping review of the
      association between frailty and Alzheimer's disease (AD) biomarkers in humans.
      Methods: Three databases, PubMed, PsycINFO, and Embase, were searched for
      articles using the following search terms: "frail elderly", "Alzheimer's
      disease", "dementia biomarkers" and their synonyms. Inclusion was limited to
      original research in humans published before 2017, which included a frailty
      measure and AD biomarker (fluid markers, neuroimaging, and neuropathology).
      Results: Five hundred twenty-two articles were identified and screened; 10 were
      included. Most were cross-sectional (n = 6), measured the frailty phenotype (n =
      6), and included people with dementia (n = 7). Biomarkers examined were
      postmortem AD pathology (n = 3), brain atrophy (n = 5), and in vivo fluid markers
      (n = 2). Eight studies reported that increased frailty was associated with at
      least one biomarker abnormality. Discussion: Evidence is limited and suffers from
      design limitations but suggests that frailty and AD biomarkers are closely
      linked. Longitudinal research examining multiple biomarkers and frailty is
      warranted.

PMID- 30094327
TI  - Better prognostic accuracy in younger mild cognitive impairment patients with
      more years of education.
AB  - Introduction: Age and years of education influence the risk of dementia and may
      impact the prognostic accuracy of mild cognitive impairment subtypes. Methods:
      Memory clinic patients without dementia (N = 358, age 64.0 +/- 7.9) were
      stratified into four groups based on years of age (<=64 and >=65) and education
      (<=12 and >=13), examined with a neuropsychological test battery at baseline and
      followed up after 2 years. Results: The prognostic accuracy of amnestic multi
      domain mild cognitive impairment for dementia was highest in younger patients
      with more years of education and lowest in older patients with fewer years of
      education. Conversely, conversion rates to dementia were lowest in younger
      patients with more years of education and highest in older patients with fewer
      years of education. Discussion: Mild cognitive impairment subtypes and
      demographic information should be combined to increase the accuracy of prognoses
      for dementia.

PMID- 30094328
TI  - Amyloid positron emission tomography candidates may focus more on benefits than
      risks of results disclosure.
AB  - Introduction: Given mounting calls to disclose biomarker test results to research
      participants, we explored factors underlying decisions by patients with mild
      cognitive impairment to receive amyloid imaging results. Methods: Prospective,
      qualitative interviews were conducted with 59 participants (30 = mild cognitive
      impairment patients, 29 = care partners) from the scan arm of a randomized
      controlled trial on the effects of amyloid PET results disclosure in an Alzheimer
      Disease Research Center setting. Results: Sixty-three percent of the participants
      were female, with an average age of 72.9 years, and most had greater than a high
      school level of education (80%). Primary motivations included: (1) better
      understanding one's mild cognitive impairment etiology and prognosis to plan
      ahead, and (2) learning one's brain amyloid status for knowledge's sake,
      regardless of whether the information is actionable. Most participants
      demonstrated an adequate understanding of the scan's limitations, yet instances
      of characterizing amyloid PET as a definitive test for Alzheimer's disease
      occurred. Mention of potential drawbacks, such as negative psychological
      outcomes, was minimal, even among care partners. Discussion: Findings demonstrate
      a risk of disproportionate focus on possible benefits of testing among amyloid
      scan candidates and suggest a need to clearly emphasize the limitations of
      amyloid PET when counseling cognitively impaired patients and their families
      before testing. Future research should examine whether minimizing drawbacks at
      the pre-imaging stage has adverse consequences on results disclosure.

PMID- 30094330
TI  - Intranasal rifampicin for Alzheimer's disease prevention.
AB  - Introduction: Oral rifampicin has been shown to significantly reduce amyloid beta
      (Abeta) and tau pathologies in mice. However, it shows occasional adverse effects
      such as liver injury in humans, making its use difficult for a long period.
      Methods: To explore safer rifampicin treatment, APPOSK mice, a model of
      Alzheimer's disease, were treated with rifampicin for 1 month via oral,
      intranasal, and subcutaneous administration, and its therapeutic efficacy and
      safety were compared. Results: Intranasal or subcutaneous administration of
      rifampicin improved memory more effectively than oral administration. The
      improvement of memory was accompanied with the reduction of neuropathologies,
      including Abeta oligomer accumulation, tau abnormal phosphorylation, and synapse
      loss. Serum levels of a liver enzyme significantly rose only by oral
      administration. Pharmacokinetic study revealed that the level of rifampicin in
      the brain was highest with intranasal administration. Discussion: Considering its
      easiness and noninvasiveness, intranasal administration would be the best way for
      long-term dosing of rifampicin.

PMID- 30094329
TI  - The My Active and Healthy Aging (My-AHA) ICT platform to detect and prevent
      frailty in older adults: Randomized control trial design and protocol.
AB  - Introduction: Frailty increases the risk of poor health outcomes, disability,
      hospitalization, and death in older adults and affects 7%-12% of the aging
      population. Secondary impacts of frailty on psychological health and
      socialization are significant negative contributors to poor outcomes for frail
      older adults. Method: The My Active and Healthy Aging (My-AHA) consortium has
      developed an information and communications technology-based platform to support
      active and healthy aging through early detection of prefrailty and provision of
      individually tailored interventions, targeting multidomain risks for frailty
      across physical activity, cognitive activity, diet and nutrition, sleep, and
      psychosocial activities. Six hundred adults aged 60 years and older will be
      recruited to participate in a multinational, multisite 18-month randomized
      controlled trial to test the efficacy of the My-AHA platform to detect prefrailty
      and the efficacy of individually tailored interventions to prevent development of
      clinical frailty in this cohort. A total of 10 centers from Italy, Germany,
      Austria, Spain, United Kingdom, Belgium, Sweden, Japan, South Korea, and
      Australia will participate in the randomized controlled trial. Results: Pilot
      testing (Alpha Wave) of the My-AHA platform and all ancillary systems has been
      completed with a small group of older adults in Europe with the full randomized
      controlled trial scheduled to commence in 2018. Discussion: The My-AHA study will
      expand the understanding of antecedent risk factors for clinical frailty so as to
      deliver targeted interventions to adults with prefrailty. Through the use of an
      information and communications technology platform that can connect with multiple
      devices within the older adult's own home, the My-AHA platform is designed to
      measure an individual's risk factors for frailty across multiple domains and then
      deliver personalized domain-specific interventions to the individual. The My-AHA
      platform is technology-agnostic, enabling the integration of new devices and
      sensor platforms as they emerge.

PMID- 30094332
TI  - Community-based serious illness care for patients with dementia.

PMID- 30094331
TI  - TOMMORROW neuropsychological battery: German language validation and normative
      study.
AB  - Introduction: Assessment of preclinical Alzheimer's disease (AD) requires
      reliable and validated methods to detect subtle cognitive changes. The battery of
      standardized cognitive assessments that is used for diagnostic criteria for mild
      cognitive impairment due to AD in the TOMMORROW study have only been fully
      validated in English-speaking countries. We conducted a validation and normative
      study of the German language version of the TOMMORROW neuropsychological test
      battery, which tests episodic memory, language, visuospatial ability, executive
      function, and attention. Methods: German-speaking cognitively healthy controls
      (NCs) and subjects with AD were recruited from a memory clinic at a Swiss medical
      center. Construct validity, test-retest, and alternate form reliability were
      assessed in NCs. Criterion and discriminant validities of the cognitive measures
      were tested using logistic regression and discriminant analysis. Cross-cultural
      equivalency of performance of the German language tests was compared with English
      language tests. Results: A total of 198 NCs and 25 subjects with AD (aged 65-88
      years) were analyzed. All German language tests discriminated NCs from persons
      with AD. Episodic memory tests had the highest potential to discriminate with
      almost twice the predictive power of any other domain. Test-retest reliability of
      the test battery was adequate, and alternate form reliability for episodic memory
      tests was supported. For most tests, age was a significant predictor of group
      effect sizes; therefore, normative data were stratified by age. Validity and
      reliability results were similar to those in the published US cognitive testing
      literature. Discussion: This study establishes the reliability and validity of
      the German language TOMMORROW test battery, which performed similarly to the
      English language tests. Some variations in test performance underscore the
      importance of regional normative values. The German language battery and
      normative data will improve the precision of measuring cognition and diagnosing
      incident mild cognitive impairment due to AD in clinical settings in German
      speaking countries.

PMID- 30094334
TI  - Conventional Troponin-I versus high-sensitivity troponin-T: Performance and
      incremental prognostic value in non-ST-elevation acute myocardial infarction
      patients with negative CK-MB based on a real-world multicenter cohort.

PMID- 30094333
TI  - Liver stiffness and arterial stiffness/abnormal central hemodynamics in the early
      stage of heart failure.
AB  - Background: It remains to be clarified whether liver stiffness is a direct risk
      factor for heart failure (HF) or whether its association with HF is mediated by
      vascular damage. We conducted cross-sectional and prospective longitudinal
      studies to examine whether fibrosis 4 score (FIB-4 score) is directly associated
      with the serum NT-pro-BNP levels or the association is mediated by arterial
      stiffness and/or abnormal central hemodynamics. Methods and results: In 3040
      health Japanese subjects with serum NT-pro-BNP levels < 125 pg/ml, the FIB-4
      score was calculated, and the serum NT-pro-BNP levels, brachial-ankle pulse wave
      (baPWV) velocity and radial augmentation index (rAI) were measured. These
      parameters were measured again after a 3-year interval in 2135 subjects.
      Multivariate linear regression analysis demonstrated a significant cross
      sectional association of the FIB-4 scores with the log-transformed the serum NT
      pro-BNP levels (beta = 0.08, p < 0.01), but not with the baPWV or rAI. The change
      of serum NT-pro BNP levels during the study period was significantly higher in
      subjects with increase of the FIB-4 score during the study period (8.2 +/- 22.5
      pg/ml) than that in those with decrease/no change (5.4 +/- 22.3 pg/ml) (p <
      0.05). Conclusion: Liver stiffness may have a significant direct association with
      the development of HF from the early stage, without the mediation of arterial
      stiffness and/or abnormal central hemodynamics. Therefore, the FIB-4 score
      appears to serve as a direct risk factor for HF from the early stage, and its
      association with HF may not be mediated by vascular damages.

PMID- 30094337
TI  - Robotic Kidney Transplantation from a Brain-Dead Deceased Donor in a Patient with
      Autosomal Dominant Polycystic Kidney Disease: First Case Report.
AB  - Background: Autosomal dominant polycystic kidney disease (ADPKD) is a common
      cause of end-stage renal disease (ESRD) and may pose significant technical
      challenges for kidney transplantation. Recently, robot-assisted kidney
      transplantation (RAKT) has been shown to achieve excellent patient and graft
      outcomes while reducing surgical morbidity. However, the vast majority of RAKT
      performed so far were from living donors and no studies reported the outcomes of
      RAKT in patients with ADPKD. Case Presentation: Herein, we describe the first
      successful case of RAKT from a brain-dead deceased donor in a 37-year-old patient
      with ESRD due to ADPKD. Conclusion: Our case highlights that RAKT can be safely
      performed by experienced robotic surgeons even in selected complex recipients
      such as patients with ADPKD and using grafts from deceased donors.

PMID- 30094336
TI  - Necrotic Lesions Following Elective Urological Surgery in an Infant.
AB  - Case Report  An 11-month-old female infant presented on the first postoperative
      (PO) day following an elective pyeloplasty, a dark bluish erythema of her
      lumbotomy wound, plus a satellite lesion of the same characteristics. Fever and
      sepsis developed, and despite broad spectrum antibiotics (meropenem and
      vancomycin) were started, a diagnosis of necrotizing soft-tissue infection (NSTI
      or necrotizing fasciitis) was established. Surgical debridement of both lesions
      was performed on day 3 PO, and a surgical contamination (ring retractor blade)
      was suspected, due to the particular geography of the lesion. Urine and blood
      cultures yielded no bacteria, but tissue culture grew Pseudomonas aeruginosa . At
      PO 6th day, lesions still appeared exudative and poorly perfused, so vacuum
      assisted therapy (VAT) treatment was started. Exudate control, perfusion, and
      granulation improved in consecutive days, which permitted direct closure (no
      graft needed) at PO day 12. Discussion   P. aeruginosa can be a fatal cause of
      type I NSTI. It has been reported rarely in adult series, with a prevalence of
      4%, but it can be a major pathogen in pediatric NSTI. Added to an early
      recognition, aggressive surgery and debridement are required, in combination with
      antibiotic therapy, to limit the spread of the infection. In our case, despite
      surgical debridement being performed on day 3 PO, both wounds maintained scarce
      perfusion, and debris and exudate were poorly controlled with usual silver foams
      and daily nursery cures. VAT pediatric device was then added, which rapidly
      improved surgical bed, enhancing tissue perfusion and granulation in the
      following days.

PMID- 30094338
TI  - Correlates of Not Using Antiretroviral Therapy Among Transwomen Living with HIV:
      The Unique Role of Personal Competence.
AB  - Purpose: This study tested three psychosocial measures for their potential to
      serve as counseling goals for promoting ART to transgender women living with HIV
      (TWLH). Methods: Among 69 TWLH, 17.4% were not taking ART; these volunteers were
      compared to the remainder using multivariate regression analyses. Results: Only
      one psychosocial measure achieved significance: Personal Competence (Adjusted
      Odds Ratio = 0.80, 95% CI = 0.67-0.97, P = 0.02). Because this was a continuous
      measure, assessed on a 7-point scale, the protective adjusted odds ratio of 0.80
      represents a 20% reduction in the odds of not taking ART for each unit of
      increase in this construct. Conclusion: Findings suggest a potential counseling
      goal for TWLH not taking ART.

PMID- 30094339
TI  - Molecular Karyotyping in Children and Adolescents with Gender Dysphoria.
AB  - Purpose: The presence of a disorder of sexual development (DSD) acts as a
      diagnostic specifier for gender dysphoria (GD) under DSM-5, while the
      International Classification of Diseases (ICD)-10 specifically states that its
      equivalent diagnosis, gender identity disorder (GID), must not be the result of a
      chromosomal abnormality. For these reasons, routine karyotyping has been
      previously advocated in the clinical work-up of children and adolescents with
      suspected GD or GID. However, the utility of such testing remains unclear.
      Methods: The results of routine molecular karyotyping were analyzed in 128
      patients attending our Australian statewide pediatric gender service from 2013 to
      2016. Karyotyping was performed using an Illumina BeadChip platform and provided
      information on both sex chromosome composition and copy number variation (CNV).
      Results: No sex chromosome abnormalities directly suggestive of a DSD were
      discovered. The rate of CNVs among our patient cohort was 8.6% (11/128), similar
      to that previously reported for the general population. Unexpectedly, three trans
      male patients shared the same CNV, involving an almost identical 400 kbp deletion
      on chromosome 15q11.2. The frequency of this deletion within birth-assigned
      females in our cohort (3/69; 4.3%) was significantly higher than that within
      local control populations (0.3%; Fisher's exact test p-value=0.002), suggesting a
      possible association between 15q11.2 deletions and trans male identity.
      Conclusion: Routine molecular karyotyping failed to detect any occult DSD and
      indicated that the rate of CNVs was similar to that of the general population.
      Given these findings, we suggest that molecular karyotyping has minimal clinical
      utility in the routine management of children and adolescents with GD.

PMID- 30094340
TI  - Effect of an elongation bending derotation brace on the infantile or juvenile
      scoliosis.
AB  - Background: A wide variety of braces are commercially available designed for the
      adolescent idiopathic scoliosis (AIS), but very few braces for infantile
      scoliosis (IS) or juvenile scoliosis (JS). The goals of this study were: 1) to
      briefly introduce an elongation bending derotation brace (EBDB) in the treatment
      of IS or JS; 2) to investigate changes of Cobb angles in the AP view of X-ray
      between in and out of the EBDB at 0, 3, 6, 9, and 12 months; 3) to compare
      differences of Cobb angles (out of brace) in 3, 6, 9, and12 month with the
      baseline; 4) to investigate changes (out of brace) in JS and IS groups
      separately. Methods: Thirty-eight patients with IS or JS were recruited
      retrospectively for this study. Spinal manipulation was performed using a
      stockinet. This was done simultaneously with a surface topography scan. The
      procedure was done in the operating room for IS, or in a clinical setting for JS.
      The brace was edited and fabricated using CAD/CAM method. Radiographs were
      recorded in and out of bracing approximately every 3 months from baseline to 12
      months. A linear mixed effects model was used to compare in and out of bracing,
      and out of brace Cobb angle change over the 12 month period. Results: Overall,
      37.5% of curves are corrected and 37.5% stabilized after 12 months (Thoracic
      curves 48% correction, 19% stabilization; thoracolumbar curves 33% correction,
      56% stabilization and lumbar curves 29% correction, 50% stabilization). The
      juvenile group had 25.7% correction and 42.9% stabilization, while the infantile
      group had 50% correction and 32.1% stabilization. There was a significant Cobb
      angle in-brace reduction in the thoracic (11 degrees ), thoracolumbar (12 degrees
      ), and lumbar (12 degrees ) (p < 0.001). There was no statistically significant
      change in out of brace Cobb angle from baseline to month 12 (p > 0.05). No
      patients required surgery within the 12 month span. Conclusions: This study
      describes a new clinical protocol in the development of the EBDB. Short-term
      results show brace is effective in preventing IS or JS curve progression over a
      12 month span.

PMID- 30094335
TI  - Neuro-Cognitive Effects of Acute Tyrosine Administration on Reactive and
      Proactive Response Inhibition in Healthy Older Adults.
AB  - The aging brain is characterized by altered dopamine signaling. The amino acid
      tyrosine, a catecholamine precursor, is known to improve cognitive performance in
      young adults, especially during high environmental demands. Tyrosine
      administration might also affect catecholamine transmission in the aging brain,
      thereby improving cognitive functioning. In healthy older adults, impairments
      have been demonstrated in two forms of response inhibition: reactive inhibition
      (outright stopping) and proactive inhibition (anticipatory response slowing)
      under high information load. However, no study has directly compared the effects
      of a catecholamine precursor on reactive and load-dependent proactive inhibition.
      In this study we explored the effects of tyrosine on reactive and proactive
      response inhibition and signal in dopaminergically innervated fronto-striatal
      regions. Depending on age, tyrosine might lead to beneficial or detrimental
      neurocognitive effects. We aimed to address these hypotheses in 24 healthy older
      human adults (aged 61-72 years) using fMRI in a double blind, counterbalanced,
      placebo-controlled, within-subject design. Across the group, tyrosine did not
      alter reactive or proactive inhibition behaviorally but did increase fronto
      parietal proactive inhibition-related activation. When taking age into account,
      tyrosine affected proactive inhibition both behaviorally and neurally.
      Specifically, increasing age was associated with a greater detrimental effect of
      tyrosine compared with placebo on proactive slowing. Moreover, with increasing
      age, tyrosine decreased fronto-striatal and parietal proactive signal, which
      correlated positively with tyrosine's effects on proactive slowing. Concluding,
      tyrosine negatively affected proactive response slowing and associated fronto
      striatal activation in an age-dependent manner, highlighting the importance of
      catecholamines, perhaps particularly dopamine, for proactive response inhibition
      in older adults.

PMID- 30094341
TI  - Managing alarm systems for quality and safety in the hospital setting.
AB  - Objective: To provide an overview of documented studies and initiatives that
      demonstrate efforts to manage and improve alarm systems for quality in healthcare
      by human, organisational and technical factors. Methods: A literature review, a
      grey literature review, interviews and a review of alarm-related standards (IEC
      60601-1-8, IEC 62366-1:2015 and ANSI/Advancement of Medical Instrumentation HE
      75:2009/2013) were conducted. Qualitative analysis was conducted to identify
      common themes of improvement elements in the literature and grey literature
      reviews, interviews and the review of alarm-related standards. Results: 21
      articles and 7 publications on alarm quality improvement work were included in
      the literature and grey literature reviews, in which 10 themes of improvement
      elements were identified. The 10 themes were categorised into human factors
      (alarm training and education, multidisciplinary teamwork, alarm safety culture),
      organisational factors (alarm protocols and standard procedures, alarm assessment
      and evaluation, alarm inventory and prioritisation, and sharing and learning) and
      technical factors (machine learning, alarm configuration and alarm design). 26
      clinicians were interviewed. 9 of the 10 themes were identified from the
      interview responses. The review of the standards identified 3 of the 10 themes.
      The study findings are also presented in a step-by-step guide to optimise
      implementation of the improvement elements for healthcare organisations.
      Conclusions: Improving alarm safety can be achieved by incorporating human,
      organisational and technical factors in an integrated approach. There is still a
      gap between alarm-related standards and how the standards are translated into
      practice, especially in a clinical environment that uses multiple alarming
      medical devices from different manufacturers. Standardisation across devices and
      manufacturers and the use of machine learning in improving alarm safety should be
      discussed in future collaboration between alarm manufacturers, end users and
      regulators.

PMID- 30094342
TI  - Optimising the mandatory reporting process for drivers admitted to an inpatient
      stroke rehabilitation unit.
AB  - Ontario physicians are legally obligated to report patients who may be medically
      unfit to drive to the Ministry of Transportation of Ontario (MTO). Currently at
      Toronto Rehabilitation Institute (TRI), there are no standardised processes for
      MTO reporting, resulting in inconsistent communication regarding driving with
      patients and between healthcare providers, redundant assessments and ultimately
      reduced patient satisfaction. TRI received 10 patient complaints regarding the
      driving reporting process in the 5 years prior to this project and a large number
      of patients were not being reported appropriately. The project aim was to use
      Lean Methods to achieve 100% reporting and optimise communication and education
      of drivers admitted to a 23-bed inpatient stroke rehabilitation unit.
      Interventions included process mapping, identification of wasteful steps and
      implementation of a standard work. Chart audits before and after implementation
      were performed. Value stream process mapping identified inconsistent reporting
      procedures and lack of use of the government-issued driver reporting form.
      Following implementation of standard work processes, use of the MTO Medical
      Conditions Report Form increased from 0% to 100%. Indication of whether drivers
      were reported to the MTO in Physical Medicine & Rehabilitation consultation notes
      increased from 50% to 91%. Identifying reported drivers in the discharge summary,
      of which patients receive a copy at the time of discharge, increased from 0% to
      90%. Physician satisfaction with the new standard work process was qualitatively
      assessed to be high, with no negative impacts reported. Lean methodology was
      effective for increasing the usage of the MTO Medical Conditions Report Form,
      documenting driver status in the initial Physical Medicine & Rehabilitation
      consultation and indicating MTO reporting status in the discharge summary.
      Communication between healthcare providers regarding patients' driving status has
      been successfully standardised, resulting in improved coordination of care and a
      reduction in patient complaints to zero in the 14 months since implementation.

PMID- 30094343
TI  - Making the weekend work: a local quality improvement project to establish and
      improve the quality of weekend handover.
AB  - Handover is widely identified by the National Confidential Enquiry into Patient
      Outcome and Death, the Royal College of Physicians (RCP) and Health Foundation as
      an area that can lead to shortcomings in patient care. We recognised that the
      current weekend handover process in the Trauma and Orthopaedics department at
      Frimley Park Hospital was dated, time-consuming and did not promote handover of
      sufficient patient details. The Royal College of Surgeons, British Medical
      Association and RCP have guidelines on handover. Our aim was to use these to
      establish the quality of handovers and introduce methods to better the accuracy
      and effectiveness of weekend handover in the department, thus improving patient
      care and safety. Initially, we measured the quality of the existing handover
      documentation for how comprehensively it was completed. We then implemented a two
      step change, reauditing each step, resulting in a handover tool on the trust
      intranet. Finally, we repeated our audit to monitor sustainability. The 10
      categories measured were: 'Patient name', 'Date of birth', 'Hospital number',
      'Date of admission', 'Location', 'Consultant', 'Admission reason', 'Date of
      operation', 'Frequency of review' and discharge paperwork ('TTO'). The original
      handover documentation had good compliance with 'Patient name' (99%), 'Hospital
      number' (94%) and 'Admission reason' (91%) but was poor in all other categories,
      ranging from 12% to 84%. The only category that met its standard was 'Admission
      reason'. Almost every category improved with the new intranet tool. Five areas
      met their standard ('Patient name', 'Location', 'Consultant', 'Admission reason'
      and 'Frequency of review'). Specific prompts resulted in 100% compliance for
      'Frequency of review'. The poorest compliance was again seen for 'TTO' (18%). In
      a short four months, we created an intranet handover tool that resulted in
      significant and sustainable improvements in the quality, detail and accuracy of
      handovers, making identification of sick patients safer and more efficient.

PMID- 30094344
TI  - Implementation of a skilled nursing facility readmission review process.
AB  - 30-day readmissions for patients at skilled nursing facilities (SNF) are common
      and preventable. We implemented a readmission review process for patients
      readmitted from two SNFs, involving an electronic review tool and monthly
      conferences. The electronic review tool captures information related to
      preventability and factors contributing to readmission. The study included 128
      patients, readmitted within 30 days from 1 October 2015 through 1 May 2017, at a
      tertiary care academic medical centre in Boston, MA, and two partnering SNFs.
      There was a discrepancy in preventability rating between SNF and hospital
      reviewers, with 79.7% of cases rated not preventable by the SNF, and 58.6% by the
      hospital. There was moderate positive correlation between the hospital's and
      SNFs' preventability ratings (rs=0.652, p<0.001). In most cases, the SNF
      reviewers felt that no factors contributed (57.8%), and hospital reviewers felt
      that issues with end-of-life planning (14.1%) and medical complexity (12.5%) were
      major factors. Despite the lack of strong correlation between SNF and hospital
      responses, several cross-continuum quality improvement projects were developed.
      We found that implementation of a SNF readmission review process employing
      bidirectional review by SNF and hospital was feasible, and facilitated systems
      based improvement in the transition from hospital to postacute care.

PMID- 30094345
TI  - Increasing contraception use among women receiving teratogenic medications in a
      rheumatology clinic.
AB  - Teratogenic medications are often prescribed to women of childbearing age with
      autoimmune diseases. Literature suggests that appropriate use of contraception
      among these women is low, potentially resulting in high-risk unintended
      pregnancies. Preliminary review in our clinic showed suboptimal documentation of
      women's contraceptive use. We therefore designed a quality improvement initiative
      to target three process measures: documentation of contraception usage and type,
      contraception counselling and provider action after counselling. We reviewed
      charts of rheumatology clinic female patients aged 18-45 over the course of 10
      months; for those who were on teratogenic medications (methotrexate, leflunomide,
      mycophenolate and cyclophosphamide), we looked for evidence of documentation of
      contraception use. We executed multiple plan-do-study-act (PDSA) cycles to
      develop and evaluate interventions, which centred on interprofessional provider
      education, modification of electronic medical record (EMR) templates, periodic
      provider reminders, patient screening questionnaires and frequent feedback to
      providers on performance. Among eligible patients (n=181), the baseline rate of
      documentation of contraception type was 46%, the rate of counselling was 30% and
      interventions after counselling occurred in 33% of cases. Averaged intervention
      data demonstrated increased provider performance in all three domains:
      documentation of contraception type increased to 64%, counselling to 45% and
      provider action to 46%. Of the patients with documented contraceptives, 50% used
      highly effective, 27% used effective and 23% used ineffective contraception
      methods. During this project, one unintentional pregnancy occurred in a patient
      on methotrexate not on contraception. Our interventions improved three measures
      related to contraception counselling and documentation, but there remains a need
      for ongoing quality improvement efforts in our clinic. This high-risk population
      requires increased provider engagement to improve contraception compliance,
      coupled with system-wide EMR changes to increase sustainability.

PMID- 30094346
TI  - Improving access to services through a collaborative learning system at East
      London NHS Foundation Trust.
AB  - Early intervention following initial referral into healthcare services can have a
      significant impact on the prognosis and outcomes of patients. Long waiting times
      and non-attendance can have an immediate and enduring negative impact on patients
      and healthcare service providers. The traditional management options in reducing
      waiting times have largely revolved around setting performance targets, providing
      financial incentives or additional resourcing. This large-scale quality
      improvement project aimed to reduce waiting times from referral to first
      appointment and non-attendance for a wide range of services providing primary and
      secondary care mental health and community health services at East London NHS
      Foundation Trust (ELFT). Fifteen community-based teams across ELFT came together
      with the shared goal of improving access. These teams were diverse in both nature
      and geography and included adult community mental health teams, child and
      adolescent mental health services, secondary care psychological therapy services,
      memory services, a musculoskeletal physiotherapy service and a sickle cell
      service. A collaborative learning system was developed to support the teams to
      come together at regular intervals, share data, test and scale-up ideas through
      quality improvement and have access to coaching from skilled improvement advisors
      in the ELFT central quality improvement team. Over the course of the 2-year
      project, waiting time from referral to first face-to-face appointment reduced
      from an average of 60.6 days to 46.7 days (a 23% reduction), non-attendance at
      first face-to-face appointment reduced from an average of 31.7% to an average of
      20.5% (a 36% reduction), while referral volume increased from an average of 1021
      per month to an average of 1280 per month (a 25% increase).

PMID- 30094347
TI  - Effect of a Physical Activity Consultation in the Management of Adolescent
      Overweight (the PAC-MAnO project): study rationale, design and methods.
AB  - Background: Adolescent overweight is a major public health concern, as it is
      associated with several short-run and long-run adverse health outcomes.
      Inappropriate health behaviours may be at the front of this epidemic. There is
      widespread need for new strategies that may positively influence dietary and
      physical activity behaviours. This trial (NCT02941770) was designed to
      investigate the impact of a physical activity consultation, based on motivational
      interview technique, on physical activity behaviour and weight status among
      overweight adolescents followed at a tertiary paediatric care centre.
      Methods/Design: This is an ongoing non-randomised controlled clinical trial with
      a 6-month duration and follow-up at month 12. It is expected to be concluded in
      December 2018. Adolescents (n=129) aged 12-18 with a body mass index >=p85 are
      recruited and allocated into three groups: (1) control group: standard care
      (paediatric and nutrition consultations, n=43); (2) experimental group I:
      standard care plus physical activity consultation (n=43); and (3) experimental
      group II: exposure to two sessions/week of structured physical exercise, in
      addition to the standard care plus physical activity consultations (n=43). Sample
      size was calculated according to power analysis. Participants undergo a set of
      socioeconomic, anthropometric, body composition, clinical and behavioural
      (dietary and physical activity) assessments. Discussion: Adolescence is a
      critical period for the acquisition of a healthy lifestyle. The promotion of an
      active lifestyle may influence adolescents' weight status and further prevent
      multiple comorbidities. The findings of our study will provide further
      understanding on the impact of a physical activity consultation on physical
      activity behaviour and weight reduction/maintenance among overweight adolescents.
      Trial registration number: NCT02941770.

PMID- 30094348
TI  - Associations between parental mental health and other family factors and
      healthcare utilisation among children and young people: a retrospective, cross
      sectional study of linked healthcare data.
AB  - Objective: To identify the degree to which parental diagnosis of depression or
      other long-term conditions, parental health-seeking behaviours and household
      factors were associated with a healthcare utilisation among children and young
      people (CYP) (0-15 years). Design: Retrospective, cross-sectional study of
      electronic health records, from 25 252 patients registered at a large, London
      based primary care provider. The associations between children's healthcare
      utilisation and the characteristics of the child, their parents/carers and their
      household structure were examined using multivariable regression. Results:
      Controlling for parental utilisation, parental depression (vs not) was
      significantly associated with increased healthcare utilisation for CYP. Odds
      ratios for CYP with siblings=1.41 (95% CI 1.10 to 1.80) for emergency department
      (ED) attendances, 1.67 (95% CI 1.32 to 2.11) for outpatient appointments, 1.47
      (95% CI 1.07 to 2.03) for inpatient admission, and rate rato=1.28 (95% CI 1.04 to
      1.78) for general practitioner (GP) consultations.After adjusting for child and
      parental characteristics, parental general practice attendance (+1 from mean) was
      predictive of increased CYP general practice attendance, rate ratio 1.07 (95% CI
      1.06 to 1.08) for CYP with siblings. Parental ED attendance also increased the
      risk of CYP ED attendance, with OR 1.27 (95% CI 1.12 to 1.44) for CYP with
      siblings. Conclusions: Parental depression is associated with increased
      utilisation of ED, outpatient and inpatient services by CYP, as well as with
      increased GP consultations among adolescents. Our results demonstrate that
      healthcare utilisation by CYP is associated with the health-seeking behaviour of
      adults in their household.

PMID- 30094350
TI  - Correction: Drakenstein Child Health Study (DCHS): investigating determinants of
      early child development and cognition.
AB  - [This corrects the article DOI: 10.1136/bmjpo-2018-000282.].

PMID- 30094349
TI  - Testing of a synthetic phonics-based targeted reading intervention for students
      with reading difficulties in Year 1: protocol for an efficacy randomised
      controlled trial.
AB  - Introduction: Literacy is fundamental for educational achievement, and in the
      longer term contributes substantially to a range of life skills. Literacy
      difficulties during the early years of school are associated with long-term
      impacts on academic success, with differences in academic achievement sustained
      through children's schooling. Therefore, addressing literacy difficulties during
      the early years of school is essential in reducing the risk of children
      progressing onto negative academic, psychosocial and vocational trajectories.
      This trial will determine whether a phonics-based reading intervention can
      improve the reading comprehension of students identified as low-progress readers
      in the second year of primary school. Methods/design: We recruited 236 students
      fromnine schools after screening for reading difficulties in the second year of
      primary school (Year 1). Schools in Sydney and Central Coast of New South Wales
      will be invited to participate via an opt-out consent process. All children
      identified as being in the bottom 25th percentile using the Wheldall Assessment
      of Reading Lists will be eligible for the trial. These children will be
      randomised into either 'usual teaching' or 'intervention' groups. Trained school
      support teachers will deliver the MiniLit intervention. Intervention: In groups
      of four, children will complete a daily 1-hour lesson with their MiniLit teacher
      over 20 school weeks. Follow-up: Immediately after intervention completion and 6
      months later using child face-to-face assessments. Primary outcome: Reading
      comprehension at 6 months after intervention completion. The study will have an
      embedded process and cost-effectiveness evaluation. Discussion: The Building
      Better Readers trial will be the first efficacy randomised controlled trial
      comparing usual teaching with a phonics-based reading intervention for children
      with reading difficulties in Year 1 of primary school in Australia. The
      randomised design will limit the effect of bias on outcomes seen in other
      studies. Trial registration number: ACTRN12617000179336.

PMID- 30094351
TI  - Live cell imaging of X chromosome reactivation during somatic cell reprogramming.
AB  - Generation of induced pluripotent stem cells (iPSCs) with naive pluripotency is
      important for their applications in regenerative medicine. In female iPSCs,
      acquisition of naive pluripotency is coupled to X chromosome reactivation (XCR)
      during somatic cell reprogramming, and live cell monitoring of XCR is potentially
      useful for analyzing how iPSCs acquire naive pluripotency. Here we generated
      female mouse embryonic stem cells (ESCs) that carry the enhanced green
      fluorescent protein (EGFP) and humanized Kusabira-Orange (hKO) genes inserted
      into an intergenic site near either the Syap1 or Taf1 gene on both X chromosomes.
      The ESC clones, which initially expressed both EGFP and hKO, inactivated one of
      the fluorescent protein genes upon differentiation, indicating that the EGFP and
      hKO genes are subject to X chromosome inactivation (XCI). When the derived
      somatic cells carrying the EGFP gene on the inactive X chromosome (Xi) were
      reprogrammed into iPSCs, the EGFP gene on the Xi was reactivated when
      pluripotency marker genes were induced. Thus, the fluorescent protein genes
      inserted into an intergenic locus on both X chromosomes enable live cell
      monitoring of XCI during ESC differentiation and XCR during reprogramming. This
      is the first study that succeeded live cell imaging of XCR during reprogramming.

PMID- 30094353
TI  - Helping patients make informed decisions. Two-year evaluation of the Gustave
      Roussy prostate cancer multidisciplinary clinic.
AB  - Objectives: The initial treatment decision for newly diagnosed non-metastatic
      prostate cancer is complex. Multiple valid approaches exist, without a clear and
      absolute consensus for every clinical scenario, and therefore specialist opinions
      may vary. Multidisciplinary consultations focusing on shared decision-making aim
      to provide an apposite tool for the initial treatment decision. We have evaluated
      the first two years of activity of the Gustave Roussy Prostate Cancer
      Multidisciplinary Clinic (PCMC), dedicated to the initial decision-making for non
      metastatic prostate cancer. Methods: PCMC consists of two consecutive specialist
      consultations with a urological surgeon and a radiation oncologist, followed by a
      dedicated Tumor Board discussion. A study questionnaire was addressed to all PCMC
      patients via postal mail. Medical notes and questionnaire responses of 195
      eligible patients were analyzed. Results: The questionnaire response rate was 69%
      (134 patients). Complete satisfaction rate was high (114 of 118 responders, 97%).
      Patients were offered new treatment options in 55% of cases, and felt better
      informed in 98% (122 of 125 responders). The double consultation was considered
      useful (124 of 129 responders, 96%). Reported feeling of active participation was
      significantly elevated (117 of 131 responders, 89%), while 46% of patients (57 of
      125) modified their decision on the management of their prostate cancer following
      their PCMC consultation. Conclusions: The experience of a multidisciplinary
      consultation in the initial management of non-metastatic prostate cancer renders
      high patient satisfaction, improves their appreciation of feeling better
      informed, promotes active participation and shared decision-making and strongly
      influences their final decision.

PMID- 30094352
TI  - Verification of HE-based CTV in laryngeal and hypopharyngeal cancer using pan
      cytokeratin.
AB  - Background: For accurate target definition, we determined margins for the
      clinical target volume (CTV) for laryngeal and hypopharyngeal cancer in computed
      tomography (CT, 4.3 mm), magnetic resonance imaging (MR, 6.1 mm) and
      fluorodeoxyglucose (FDG)-positron emission tomography (PET, 5.2 mm). Previously,
      we used Hematoxylin-eosin (HE) stained whole-mount sections of total laryngectomy
      specimens as gold standard to define CTV margins. In the present study, we
      verified the HE-based tumor delineation with staining for pan-cytokeratin,
      specific for squamous cell carcinoma. Methods: Twenty-seven patients with a T3/T4
      laryngeal hypopharyngeal tumor were included. From each patient, a total
      laryngectomy specimen was obtained. Four subsequent 3-mm thick slices containing
      tumor were selected of which 4-um thick whole-mount sections were obtained and
      stained with HE and for pan-cytokeratin CK-AE1/3. Tumors were microscopically
      delineated on both sections by an experienced head-and-neck pathologist. Tumor
      delineations were compared using the conformity index (CI) and the distance
      between both contours. Results: The CI between HE-based and CK-AE1/3-based tumor
      delineations was 0.87. The maximum and 95th percentile (p95) extent of the HE
      based tumor delineations from the CK-AE1/3-based tumor delineations were 1.7 mm
      and 0.7 mm, respectively. The maximum and p95 extent of the CK-AE1/3-based tumor
      delineations from the HE-based tumor delineations was 1.9 mm and 0.8 mm,
      respectively. Conclusions: Histopathological assessment of tumor outline on
      standard HE-stained sections is comparable to microscopic tumor extent based on
      squamous cell specific pan-cytokeratin staining. Therefore, CTV margins based on
      HE based tumor contour will be adequate.

PMID- 30094355
TI  - Painful Blue Finger-Achenbach's Syndrome: Two Case Reports.
AB  - Introduction: Herein, two cases of a rare, self resolving condition are
      described. Vascular surgeons are often called to see patients with spontaneous
      discolouration of extremities and digits. Often after extensive investigations no
      diagnosis can be ascertained and the condition resolves spontaneously. Report:
      Two cases are described here, which presented with spontaneous onset of this
      condition and after extensive testing no cause was ascertained. The condition
      resolved spontaneously. Discussion: Achenbach's syndrome is a benign, self
      limiting condition of unknown aetiology and clinicians should be aware of it to
      avoid unnecessary time consuming and expensive investigations.

PMID- 30094356
TI  - Restenosis of Aorto-renal Venous Grafts: Report of Two Patients Treated by
      Endovascular Stenting.
AB  - Introduction: Renal venous graft restenosis is an uncommon event usually
      associated with significant clinical impact. Its treatment by endovascular
      stenting is seldom reported in the literature. Report: Two cases of successful
      stenting for restenosis in aorto-renal venous grafts are described, detailing the
      technique and in one case reporting for the first time the use of a covered stent
      in this condition. Discussion: Technical success may be achieved with proper
      material selection for the patient's anatomy and with dilation at relatively high
      pressures. The use of a covered stent may provide extra safety when treating vein
      grafts.

PMID- 30094354
TI  - Physicochemical, biological, functional and toxicological characterization of the
      European follow-on glatiramer acetate product as compared with Copaxone.
AB  - For more than 20 years, Copaxone (glatiramer acetate, Teva), a non-biological
      complex drug, has been a safe and effective treatment option for multiple
      sclerosis. In 2016, a follow-on glatiramer acetate product (FOGA, Synthon) was
      approved in the EU. Traditional bulk-based methods and high-resolution assays
      were employed to evaluate the physicochemical, functional, and bio-recognition
      attributes, as well as the in vivo toxicity profile of the active substances in
      Copaxone and Synthon EU FOGA lots. These tests included quality control tests
      applied routinely in release of Copaxone lots, as well as additional
      characterization assays, gene expression studies and a rat toxicity study. Even
      though the Synthon FOGA was designed to copy and compete with Copaxone, the
      active substances were found to be similar in only 7 of the tested 14 (50%)
      methods (similar is defined as within approved specifications or within the
      inherent microheterogeneity range of tested Copaxone batches, or not showing
      statistically significant differences). With additional methods applied,
      consistent compositional differences in attributes of surface charge
      distribution, molecular size, and spatial arrangement were observed. These marked
      differences were concordantly observed with higher biological activity of some of
      the Synthon EU FOGA lots compared with Copaxone lots, including potency and
      cytotoxicity activities as well as gene expression of pathways that regulate
      apoptosis, IL-2, and inflammation signaling. These observations raise concerns
      for immunogenicity differences, particularly in (repeated) substitution settings.
      Another orthogonal finding demonstrated increased frequency of injection-site
      local toxicity observations for the Synthon EU FOGA in an in vivo daily dosing
      rat study, thus warranting further qualification of the link between
      compositional and functional differences in immunogenicity, and potential impact
      on long-term efficacy and safety.

PMID- 30094358
TI  - Comparative 3-dimensional kinematic analysis of snatch technique between top
      elite and sub-elite male weightlifters in 69-kg category.
AB  - Objective: The purpose of this study was to determine the differences in
      technical characteristics between top-elite and sub-elite male weightlifters
      performing the snatch style in the 69-kg category. The obtained results can
      provide valuable information for lower level lifters and coaches to achieve
      better competition performance by altering their training methods accordingly.
      Methods: Six top-elite and six sub-elite weightlifters participated in this
      study. The heaviest successful snatch lift from the three attempts of each
      subject was analyzed. The video data were recorded under competition conditions
      at China National Weightlifting Championship and China Olympic Trial, which were
      analyzed by SIMI degrees Motion7.50 3D analysis system. Results: The results
      showed that the maximum vertical- and relative vertical height (normalized by
      athletes' height) of the barbell, the maximal vertical linear velocity and
      acceleration of the barbell were significantly greater in top-elite lifters (p <
      0.05). In addition, the flexion angles of the knee joint were significantly
      greater in top-elite lifters during the first phase and the third phase of the
      snatch lift. Sub-elite lifters showed less flexion and significantly slower
      angular velocity in knee joint than top-elite lifters during the second phase of
      the snatch lift (p < 0.05). Conclusion: The findings of the present study
      demonstrated the differences in technical characteristics between the two levels.
      According to these findings, coaches of sub-elite lifters should focus on
      exercises suitable to the strength characteristics of the first and the third
      phase of the snatch lift. In addition, the flexor muscles of knee joint among the
      sub-elite lifters should be strengthened and the ability of generating and
      utilizing elastic energy during the second phase of the snatch lift should be
      improved.

PMID- 30094357
TI  - Mitochondrial manipulation in fertility clinics: Regulation and responsibility.
AB  - The clinical uses of cytoplasmic transfer and pronuclear transfer for infertility
      treatment have raised concerns, leading to restrictive regulatory responses in
      both the USA and China. In 2015, the UK legalized nuclear transfer from oocytes
      and zygotes to prevent the onset of serious mitochondrial disease in the children
      of affected mothers. A research team in the USA then performed egg nuclear
      transfer, with subsequent embryo transfer in Mexico, to prevent mitochondrial
      disease. A live birth resulted, but the cross-border activity attracted attention
      from regulatory authorities. In order to respond appropriately to the likelihood
      of the wider use of such mitochondrial manipulation techniques (MMT), the present
      study first surveyed countries where MMT have been clinically implemented or
      where such experimental procedures are advertised on the internet. Sixteen
      countries were selected for an analysis of the legal position regarding germline
      genetic modification and egg donation. It was found that regulation of the
      clinical use of MMT could be broken down into three categories: (i) largely
      prohibited (USA and China), (ii) not regulated (Northern Cyprus and Ukraine), and
      (iii) insufficiently regulated (the remaining 12 countries, including Mexico).
      The reasons for no or insufficient regulation included no intention to oversee
      experimental procedures, no consideration of the manipulation in eggs, unclear
      technical terms and ambiguous medical purposes. To protect future children, this
      study underscores the pressing need for regulatory frameworks with policies that
      cover MMT. Wider implications regarding the responsible implementation of
      procedures in experimental reproductive medicine are discussed.

PMID- 30094361
TI  - The effect of titanium dioxide synthesis technique and its photocatalytic
      degradation of organic dye pollutants.
AB  - Nanostructured mesoporous titanium dioxide (TiO2) particles with high specific
      surface area and average crystallite domain sizes within 2 nm and 30 nm have been
      prepared via the sol-gel and hydrothermal procedures. The characteristics of
      produced nanoparticles have been tested using X-Ray Diffraction (XRD), Brunauer
      Emmett-Teller (BET) surface area analysis, Scanning Electron Microscopy (SEM),
      Fourier Transform Infra-Red (FTIR), and Raman Spectroscopy as a function of
      temperature for their microstructural, porosity, morphological, structural and
      absorption properties. The as-synthesized TiO2 nanostructures were attempted as
      catalysts in Rhodamine B and Sudan III dyes' photocatalytic decomposition in a
      batch reactor with the assistance of Ultra Violet (UV) light. The results show
      that for catalysts calcined at 300  degrees C, ~100 % decomposition of Sudan III
      dye was observed when Hydrothermal based catalyst was used whiles ~94 %
      decomposition of Rhodamine B dye was observed using the sol-gel based catalysts.
      These synthesized TiO2 nanoparticles have promising potential applications in the
      light aided decomposition of a wide range of dye pollutants.

PMID- 30094360
TI  - Screening of microbial communities associated with endive lettuce during
      postharvest processing on industrial scale.
AB  - In this study, the composition of the microbial community on endive lettuce
      (Cichorium endivia) was evaluated during different postharvest processing steps.
      Microbial community structure was characterized by culture-dependent and culture
      independent methods. Endive lettuce was sampled exemplarily at four different
      stages of processing (raw material, cut endive lettuce, washed endive lettuce,
      and spin-dried (ready to pack) endive lettuce) and analysed by plate count
      analysis using non-selective and selective agar plates with subsequent
      identification of bacteria colonies by matrix-assisted laser
      desorption/ionization time-of light mass spectrometry (MALDI-TOF MS).
      Additionally, terminal-restriction fragment length polymorphism (TRFLP) analysis
      and 16S rRNA gene nucleotide sequence analysis were conducted. The results
      revealed structural differences in the lettuce microbiomes during the different
      processing steps. The most predominant bacteria on endive lettuce were detected
      by almost all methods. Bacterial species belonging to the families
      Pseudomonadaceae, Enterobacteriaceae, Xanthomonadaceae, and Moraxellaceae were
      detected in most of the examined samples including some unexpected potentially
      human pathogenic bacteria, especially those with the potential to build
      resistance to antibiotics (e.g., Stenotrophomonas maltophilia (0.9 % in cut
      sample, 0.4 % in spin-dried sample), Acinetobacter sp. (0.6 % in raw material,
      0.9 % in cut sample, 0.9 % in washed sample, 0.4 % in spin-dried sample),
      Morganella morganii (0.2 % in cut sample, 3 % in washed sample)) revealing the
      potential health risk for consumers. However, more seldom occurring bacterial
      species were detected in varying range by the different methods. In conclusion,
      the applied methods allow the determination of the microbiome's structure and its
      dynamic changes during postharvest processing in detail. Such a combined approach
      enables the implementation of tailored control strategies including hygienic
      design, innovative decontamination techniques, and appropriate storage conditions
      for improved product safety.

PMID- 30094363
TI  - A discrete algebraic framework for stochastic systems which yield unique and
      exact solutions.
AB  - Many physical systems exhibit random or stochastic components which shape or even
      drive their dynamic behavior. The stochastic models and equations describing such
      systems are typically assessed numerically, with a few exceptions allowing for a
      mathematically more rigorous treatment in the framework of stochastic calculus.
      However, even if exact solutions can be obtained in special cases, some results
      remain ambiguous due to the analytical foundation on which this calculus rests.
      In this work, we set out to identify the conceptual problem which renders
      stochastic calculus ambiguous, and exemplify a discrete algebraic framework
      which, for all practical intents and purposes, not just yields unique and exact
      solutions, but might also be capable of providing solutions to a much wider class
      of stochastic models.

PMID- 30094359
TI  - The impact of photofunctionalized gold nanoparticles on osseointegration.
AB  - Objectives: The aims of this study were to create a new surface topography using
      simulated body fluids (SBF) and Gold Nanoparticles (GNPs) and then to assess the
      influence of UV Photofunctionalization (PhF) on the osteogenic capacity of these
      surfaces. Materials and methods: Titanium plates were divided into six groups All
      were acid etched with 67% Sulfuric acid, 4 were immersed in SBF and 2 of these
      were treated with 10 nm GNPs. Half of the TiO2 plates were photofunctionalized to
      be compared with the non-PhF ones. Rat's bone marrow stem cells were seeded into
      the plates and then CCK8 assay, cell viability assay, immunofluorescence, and
      Scanning electron microscopy (SEM) were done after 24 hours. Gene expression
      analysis was done using real time quantitative PCR (qPCR) one week later to check
      for the mRNA expression of Collagen-1, Osteopontin and Osteocalcin. Alkaline
      phosphatase (ALP) activity was assessed after 2 weeks of cell seeding. Results:
      Our new topography has shown remarkable osteogenic potential. The new surface was
      the most biocompatible, and the 10 nm GNPs did not show any cytotoxicity. There
      was a significant increase in bioactivity, enhanced gene expressions and ALP
      activity. Conclusions: GNPs enhances osteogenic differentiation of stem cells and
      Photofunctionalizing GNPs highly increases this. We have further created a novel
      highly efficient topography which highly enhances the speed and extent of
      osseointegration. This may have great potential for improving treatment outcomes
      for implant, maxillofacial as well as orthopedic patients.

PMID- 30094364
TI  - Assessment and remediation of pollutants in Ghana's Kete-Krachi District Hospital
      effluents using granular and smooth activated carbon.
AB  - The need for simple, cheaper and high performance hospital effluent treatment
      system in Kete-Krachi District which is adjacent to the Lake Volta has
      necessitated this study. This study focuses on assessing, and treating Kete
      Krachi District Hospital effluent using packed granular (GAC) and smooth
      activated carbon (SAC). The use of activated carbon is due to its less expensive
      method of operation, the ease to prepare from local raw materials, high
      availability, and effectiveness for treating hospital effluent. The dissolved
      oxygen (DO), chemical oxygen demand (COD), biochemical oxygen demand (BOD),
      nutrient compounds (P-PO4, N-NO3), turbidity, pH, conductivity and total coliform
      parameters were investigated and later treated with the activated carbon. The
      average conductivity and P-PO4 removals were <50%. The average BOD5, COD,
      coliform, N-NO3, and turbidity removals for all the SAC treatments were 58.36%,
      62.26%, 84.39%, 83.86%, and 50.74%, respectively. The DO also improved 3.8 times
      on the average. The pH of the raw and treated samples was within the limit 6.5-9.
      The results of this study suggest that the SAC is predominantly effective for
      reducing the pollutants concentrations of the hospital effluent which can result
      in oxygen depletion, eutrophication, algal bloom and ecosystem disturbance in the
      Lake Volta. It will also decrease the susceptibility of the Kete-Krachi residents
      to waterborne diseases as the effluents seep into the Lake.

PMID- 30094362
TI  - Mindfulness-based training with transcranial direct current stimulation modulates
      neuronal resource allocation in working memory: A randomized pilot study with a
      nonequivalent control group.
AB  - Mindfulness-based training (MBT) and transcranial electrical stimulation (TES)
      methods such as direct current stimulation (tDCS) have demonstrated promise for
      the augmentation of cognitive abilities. The current study investigated the
      potential compatibility of concurrent "electrical" MBT and tDCS (or eMBT) by
      testing its combined effects on behavioral and neurophysiological indices of
      working memory (WM) and attentional resource allocation. Thirty-four healthy
      participants were randomly assigned to either a MBT task with tDCS group (eMBT)
      or an active control training task with sham tDCS (Control) group. Training
      lasted 4-weeks, with up to twenty MBT sessions and with up to eight of those
      sessions that were eMBT sessions. Electroencephalography was acquired during
      varying WM load conditions using the n-back task (1-, 2-, 3-back), along with
      performance on complex WM span tasks (operation and symmetry span) and fluid
      intelligence measures (Ravens and Shipley) before and after training. Improved
      performance was observed only on the 3-back and spatial span tasks for eMBT but
      not the Control group. During 3-back performance in the eMBT group, an increase
      in P3 amplitude and theta power at electrode site Pz was also observed, along
      with a simultaneous decrease in frontal midline P3 amplitude and theta power
      compared to the Control group. These results are consistent with the neural
      efficiency hypothesis, where higher cognitive capacity was associated with more
      distributed brain activity (i.e., increase in parietal and decrease in frontal
      amplitudes). Future longitudinal studies are called upon to further examine the
      direct contributions of tDCS on MBT by assessing the differential effects of
      electrode montage, polarity, current strength and a direct contrast between the
      eMBT and MBT conditions on performance and neuroimaging outcome data. While
      preliminary, the current results provided evidence for the potential
      compatibility of using eMBT to modulate WM capacity through the allocation of
      attention and its neurophysiological correlates.

PMID- 30094365
TI  - The role of zyxin in regulation of malignancies.
AB  - Focal adhesions are highly dynamic multi-protein complexes found at the cell
      surface and effectively link the cell's internal cytoskeleton to a complex
      mixture of macromolecules known as the extracellular matrix and mediate
      transmission of signals from the extracellular matrix to the nucleus. Zyxin is
      one of the key focal adhesion proteins and is also found to shuttle in the
      nucleus. Although the mechanism of shuttling to the nucleus unclear, it moves out
      from the nucleus through a leucine-rich nuclear export signal sequence. It is
      known to contribute to fundamental cellular activities such as cell migration,
      adhesion and proliferation by interacting with a variety of cellular proteins. It
      is also linked with a number of cancers such as melanoma, hepatocellular
      carcinoma, oral squamous-cell carcinoma, Ewing sarcoma and prostate cancer.
      However, in many cases, the precise mechanisms by which the absence or presence
      of zyxin contributes to cancer progression or suppression is unknown. Thus, more
      work is required to gain insights into how zyxin modulates cellular functions in
      relationship to cancer. This review summarises the role of zyxin in cancer, with
      an emphasis on conflicting roles in prostate cancer.

PMID- 30094366
TI  - 'My Own House, Car, My Husband, and Children': meanings of success among
      Ghanaians.
AB  - The purpose of the study was to explore the extent to which contemporary social,
      economic, and religious developments inform social constructions of success in
      Ghana. Participants, consisting of 21 females and 39 males, aged between 20 and
      70, from different educational and occupational backgrounds were interviewed
      about what they consider as success. Participants belonged to either
      Traditionally Western Mission Churches or Charismatic Christian denominations and
      were selected from three regions of Ghana. Thematic analysis revealed four
      dimensions of success: (1) Social (including marriage, children, social
      recognition, and social contribution to society); (2) Material (comprising
      meeting basic needs; economic independence; material wealth); (3) Educational;
      and (4) Religious (e.g., God's work, relationship with God). Three pathways to
      success were also observed in the data: (a) Divine blessings; (b) Adaptability;
      and (c) Striving. Discussion focuses on social, policy, counselling, and research
      implications.

PMID- 30094367
TI  - A feasibility randomised controlled trial to evaluate the effectiveness of a
      novel neuromuscular electro-stimulation device in preventing the formation of
      oedema following total hip replacement surgery.
AB  - Aim: The aim of this feasibility study was to investigate the potential role of a
      novel neuromuscular electrical stimulation (NMES) device in preventing the
      formation of oedema following total hip replacement (THR). Methods: Successive
      primary THR patients were recruited into a randomised controlled trial.
      Participants were randomised to wear either the NMES device or compression
      stockings continually from post-surgery until discharge.The main outcome measure
      was presence of lower limb oedema, assessed by taking measurements of the
      circumference of the ankle, knee and thigh on the operated leg and non-operated
      leg, pre-operatively, post-operatively, at two days post-operatively and every
      day until discharge. Secondary objectives were to compare adverse events, the
      presence of asymptomatic and symptomatic deep vein thrombosis (DVT) and device
      tolerability between groups. Results: Data from 40 participants were analysed
      (NMES (n = 20), compression stockings (n = 20)). The NMES group had significantly
      less oedema and the device was found to be tolerable and safe. Conclusion: The
      results of this study suggest that the NMES is a safe and well tolerated
      alternative to compression stockings, which should be considered by clinicians
      seeking the additional benefit of reducing post-operative oedema. In addition the
      NMES device should be considered as part of a DVT prophylaxis.

PMID- 30094368
TI  - Experimental and numerical modeling of creep in different types of concrete.
AB  - Creep in concrete, play a critical role in estimating losses in prestressed
      concrete structures, such as bridge girders, nuclear containment vessels, etc.
      The present study aims at investigating the creep under various environmental
      conditions in different types of concrete made with different ingredients using
      an experimental and numerical approach. Seven different concrete mixes have been
      made for this purpose and among the seven mixes, three mixes are self compacted
      concrete mixes (35 MPa, 55 MPa and 70 MPa), a high volume fly ash concrete mix
      (45 MPa), two mixes of normally vibrated ordinary Portland cement (OPC) concrete
      mixes (35 MPa and 45 MPa) and a heavy density concrete (25 MPa). Studies have
      been carried out at temperature of 25  degrees C and two relative humidity (RH)
      conditions (RH of 60% and 70%). An analytical model has been developed to
      simulate the drying phenomena in concrete based on a poromechanics approach. The
      hydration effects in blended cements (containing mineral admixture) is considered
      while developing the model. The proposed model is capable of predicting the
      degree of hydration, temperature and relative humidity (RH) over the continuum
      that required for estimating the creep strain. Micro prestress solidification
      (MPS) is used to estimate the creep strain. It is found that the proposed model
      is able to predict the drying phenomena and creep strain in various concretes,
      and which is in good agreement with the corresponding experimental results. It is
      found that heavy density concrete shows a higher creep strain than the other
      concretes. This may be due to the lower porosity of hematite aggregate. Further
      adding fly ash as a mineral admixture to concrete mix reduces the creep. Creep in
      a reinforced concrete (RCC) beam tested under sustained loading and reported in
      the literature is simulated using the present model and it is seen that the model
      predictions are in good agreement with the test data.

PMID- 30094369
TI  - Factors that influence quality and yield of circulating-free DNA: A systematic
      review of the methodology literature.
AB  - Background: Circulating-free DNA (cfDNA) is under investigation as a liquid
      biopsy of cancer for early detection, monitoring disease progression and
      therapeutic response. This systematic review of the primary cfDNA literature aims
      to identify and evaluate factors that influence recovery of cfDNA, and to outline
      evidence-based recommendations for standardization of methods. Methods: A search
      of the Ovid and Cochrane databases was undertaken in May 2018 to obtain relevant
      literature on cfDNA isolation and quantification. Retrieved titles and abstracts
      were reviewed by two authors. The factors evaluated include choice of specimen
      type (plasma or serum); time-to-processing of whole blood; blood specimen tube;
      centrifugation protocol (speed, time, temperature and number of spins); and
      methods of cfDNA isolation and quantification. Findings: Of 4,172 articles
      identified through the database search, 52 proceeded to full-text review and 37
      met the criteria for inclusion. A quantitative analysis was not possible, due to
      significant heterogeneity in methodological approaches between studies.
      Therefore, included data was tabulated and a textual qualitative synthesis
      approach was taken. Interpretation: This is the first systematic review of
      methodological factors that influence recovery and quantification of cfDNA,
      enabling recommendations to be made that will support standardization of
      methodological approaches towards development of blood-based cancer tests.

PMID- 30094370
TI  - DTI-based upper limit of voxel free water fraction.
AB  - Background: Free water (FW) in neuroimaging is non-flowing extracellular water in
      the cranium and brain tissue, and includes both cerebral spinal fluid (CSF) and
      fluid in intercellular space or edema. For a region such as a voxel (spatial unit
      of measurement in neuroimaging), the FW fraction is defined as the volume
      fraction of FW within that volume. Quantifying the FW fraction allows estimating
      contamination by fluid of neuroimaging or magnetic resonance spectroscopy
      measurements within a voxel. New method: An upper limit to the fraction of FW
      within a voxel, based on any diffusion tensor imaging (DTI) sequence including a
      standard single shell at one b-value, can be derived from the standard diffusion
      tensor by scaling the third eigenvalue of the diffusion tensor. Assuming a two
      compartment model, the diffusivity of a voxel is a combination of tissue and FW
      diffusivity. FW fraction is FW volume divided by voxel volume. Assuming FW
      diffuses equally in all directions, the diffusivity component is representable by
      a single, non-tensor diffusivity value. Since the diffusivity of water is known
      for a given temperature, and brain temperature is relatively constant, the FW
      diffusivity value can be assumed constant. The third eigenvector of the voxel
      diffusion tensor is the direction of least diffusivity and since the FW component
      of diffusivity is equal in all directions, we show that FW diffusivity cannot be
      lower than the third eigenvalue. Assuming FW contributes proportionally to voxel
      diffusivity, we show that the third eigenvalue divided by water diffusivity (as a
      constant based on known water diffusivity at 36.7  degrees C) forms an upper
      limit on the FW-fraction (fUL ). Results: We calculated fUL for 384 subjects from
      the IXI dataset. Values mostly ranged from 0.1 to 0.6, and were closely related
      to radial diffusivity.Comparison with Existing Methods:fUL is easily calculated
      from any DTI data, but is not a true estimate of FW-fraction. Conclusions: The
      fUL measure offers a starting point in calculating the true FW-fraction of a
      voxel, or an easy-to-calculate voxel characteristic.

PMID- 30094372
TI  - Total cost of risk for privatized electric power generation under pipeline
      vandalism.
AB  - Gas pipeline vandalism is a huge threat factor to steady electricity generation
      and energy materials flow in the power sector of Nigeria. It imposes huge cost of
      risk to that sector. Due to incessant pipeline vandalism, power availability is
      subject to elements of chance and with undesired out comes that adversely impact
      on power generation value chain. To this end, this study seeks to develop a model
      for estimating the cost of risk to a power generation company (Genco) and
      calculating plant unavailability indices by applying the dispersion technique.
      Applying the dispersion technique is innovative and differentiates the current
      methodology from other works on the subject area concerned. The probability and
      impact of failure alongside the variances and standard deviations of the
      parameters were derived. Cost to the Genco was obtained by multiplying fuel
      utilization ratio by unsupplied power and associated differential between price
      of electricity (output) and price of its primary fuel. Results showed that the
      lost megawatt hours (MWh) standard deviation, delta, of the case study plant is
      48,176.776 MWh. During the 2010 to 2012 periods, the resultant risk to the Genco
      was estimated to be ? 45,399 per MWh, ? 42,022 per MWh and ? 42,832 per MWh with
      the exchange rate as ?150/$, ?155/$ and ?159/$ respectively. To bridge a research
      gap based on literature, total cost index and model have been developed for
      measurement of impact or loss suffered as a result of vandalism. Inclusion of
      reliability index in the algorithm is a novelty as it allows measurement of level
      of system performance and its vulnerability to vandalization. The information
      will be of immense benefit to private investors in the power sector who have to
      make decisions over management of electricity generation in Nigeria based on
      imperfect information, following the privatization exercise.

PMID- 30094373
TI  - Thrust and torque force analysis in the drilling of aramid fibre-reinforced
      composite laminates using RSM and MLPNN-GA.
AB  - Aramid Fibre Reinforced Plastic composites are difficult to be drilled due to
      anisotropic material properties. Currently, soft computing techniques are used as
      alternatives to conventional mathematical models, which is robust and can deal
      with inaccuracy and uncertainty. In this paper, drilling of Aramid Fibre
      Reinforced Plastics (AFRPs) was carried out using Taguchi L54 experimental
      layout. Drilling tool used in this experiment was solid carbide. The purpose of
      this study was to find optimum combination of drilling parameters to obtain
      minimum thrust and torque force to reduce the delamination. Also, this paper
      proposed a prediction model of Multilayer Perception Neural Network optimized by
      Genetic Algorithm (MLPNN-GA). Moreover, RSM technique was used to evaluate the
      influence of process parameters (spindle speed, feed rate, drill point angle and
      drill diameter on thrust force and torque. The prediction capability of both RSM
      and MLPNN-GA was compared with Response optimizer for thrust force and torque.
      The investigation demonstrated that drill point angle is the primary factor
      affecting thrust force and drill diameter influences the torque force on the
      drill bit. Overall, this study recommends the use of high speed and low feed
      combination and drill point angles of 90 degrees -118 degrees  to reduce the
      delamination of the materials in the drilling of AFRP composites.

PMID- 30094371
TI  - Role of the vacuolar ATPase in the Alphavirus replication cycle.
AB  - We have shown that Alphaviruses can enter cells by direct penetration at the
      plasma membrane (R. Vancini, G. Wang, D. Ferreira, R. Hernandez, and D. Brown, J
      Virol, 87:4352-4359, 2013). Direct penetration removes the requirement for
      receptor-mediated endocytosis exposure to low pH and membrane fusion in the
      process of RNA entry. Endosomal pH as well as the pH of the cell cytoplasm is
      maintained by the activity of the vacuolar ATPase (V-ATPase). Bafilomycin is a
      specific inhibitor of V-ATPase. To characterize the roll of the V-ATPase in viral
      replication we generated a Bafilomycin A1(BAF) resistant mutant of Sindbis virus
      (BRSV). BRSV produced mature virus and virus RNA in greater amounts than parent
      virus in BAF-treated cells. Sequence analysis revealed mutations in the E2
      glycoprotein, T15I/Y18H, were responsible for the phenotype. These results show
      that a functional V-ATPase is required for efficient virus RNA synthesis and
      virus maturation in Alphavirus infection.

PMID- 30094374
TI  - Influence of alternative soil amendments on mycorrhizal fungi and cowpea
      production.
AB  - Alternative soil amendments (worm compost, pyrolyzed carbon [biochar]) and crop
      symbioses with arbuscular mycorrhizal (AM) fungi have the potential to reduce
      food production costs while promoting sustainable agriculture by improving soil
      quality and reducing commercial (N and P) fertilizer use. Our greenhouse studies
      investigated the influence of alternative soil amendments on AM fungi associated
      with cowpea (Vigna unguiculata [L.] Walp.) and common bean (Phaseolus vulgaris
      L.) by examining productivity and plant nutrition. We conducted an experiment to
      select a cowpea or common bean genotype based on AM fungal colonization, seed
      production, and seed nutritional content. We then grew the selected cowpea
      genotype (Resina) in low-fertility soil with 10 different soil amendments
      (combinations of biochar, worm compost, and/or commercial fertilizers) plus a non
      amended control. There were no significant differences in AM fungal colonization
      of cowpea plants grow with different soil amendments. However, an amendment blend
      containing worm compost, biochar, and 50% of the typically recommended commercial
      fertilizer rate produced plants with similar aboveground biomass, protein
      concentration, and total protein production, with increased tissue K, P, and Zn
      concentration and total content, compared to plants receiving only the
      recommended (100%) rate of commercial fertilizer. As previous research links
      uptake of P and Zn with plant-mycorrhizal symbioses, our results indicate cowpea
      nutritional benefits may be derived from AM partnership and alternative soil
      amendments. These synergies between alternative soil amendments and AM fungi may
      help reduce farm costs while maintaining or improving crop yield and nutrition,
      thus increasing global food and nutrition security.

PMID- 30094375
TI  - afpCOOL: A tool for antifreeze protein prediction.
AB  - Various cold-adapted organisms produce antifreeze proteins (AFPs), which prevent
      the freezing of cell fluids by inhibiting the growth of ice crystals. AFPs are
      currently being recognized in various organisms, living in extremely low
      temperatures. AFPs have several important applications in increasing freeze
      tolerance of plants, maintaining the tissue in frozen conditions and producing
      cold-hardy plants by applying transgenic technology. Substantial differences in
      the sequence and structure of the AFPs, pose a challenge for researchers to
      identify these proteins. In this paper, we proposed a novel method to identify
      AFPs, using supportive vector machine (SVM) by incorporating 4 types of features.
      Results of the two used benchmark datasets, revealed the strength of the proposed
      method in AFP prediction. According to the results of an independent test setup,
      our method outperformed the current state-of-the-art methods. In addition, the
      comparison results of the discrimination power of different feature types
      revealed that physicochemical descriptors are the most contributing features in
      AFP detection. This method has been implemented as a stand-alone tool, named
      afpCOOL, for various operating systems to predict AFPs with a user friendly
      graphical interface.

PMID- 30094376
TI  - An RNA-binding protein Blanks plays important roles in defining small RNA and
      mRNA profiles in Drosophila testes.
AB  - Drosophila Blanks is a testes-specific RNA-binding protein required for post
      meiotic spermiogenesis. However, Blanks's role in regulating RNA populations in
      the testes remains unknown. We performed small RNA and mRNA high-throughput
      sequencing in blanks mutant testes and controls. We identified two miRNAs, one
      siRNA, and hundreds of mRNAs that are significantly upregulated or downregulated
      in blanks mutant testes. Pathway analysis revealed that differentially expressed
      mRNAs are involved in catabolic and metabolic processes, anion and cation
      transport, mating, and reproductive behavior. Our results reveal that Blanks
      plays important roles in defining testicular small RNA and mRNA profiles.

PMID- 30094377
TI  - Treatment resistant depression incidence estimates from studies of health
      insurance databases depend strongly on the details of the operating definition.
AB  - Background: Health services databases provide population-based data that have
      been used to describe the epidemiology and costs of treatment resistant
      depression (TRD). This retrospective cohort study estimated TRD incidence and,
      via sensitivity analyses, assessed the variation of TRD incidence within the
      range of implementation choices. Methods: In three US databases widely used for
      observational studies, we defined TRD as failure of two medications as evidenced
      by their replacement or supplementation by other medications, and set maximum
      durations (caps) for how long a medication regimen could remain in use and still
      be eligible to fail. Results: TRD incidence estimates varied approximately 2-fold
      between the two databases (CCAE, Medicaid) that described socioeconomically
      different non-elderly populations; for a given cap varied 2-fold to 4-fold within
      each database across the other implementation choices; and if the cap was also
      allowed to vary, varied 6-fold or 7-fold within each database. Limitations: The
      main limitations were typical of studies from health services databases and
      included the lack of complete -rather than recent - medical histories, the
      limited amount of clinical information, and the assumption that medication
      dispensed was consumed as directed. Conclusion: In retrospective cohort studies
      from health services databases, TRD incidence estimates vary widely depending on
      the implementation choices. Unless a firm basis for narrowing the range of these
      choices can be found, or a different analytic approach not dependent on such
      choices is adopted, TRD incidence and prevalence estimates from such databases
      will be difficult to compare or interpret.

PMID- 30094378
TI  - LLC tumor cells-derivated factors reduces adipogenesis in co-culture system.
AB  - Cancer cachexia (CC) is a multifactorial syndrome with an unknown etiology. The
      primary symptom is the progressive reduction of the body weight. Recently, down
      regulation of adipogenic and lipogenic genes were demonstrated to be early
      affected during cachexia progression in adipose tissue (AT), resulting in AT
      remodeling. Thus, this study aimed to evaluate in a co-culture system the
      influence of the Lewis Lung Carcinoma (LLC) tumor cells (c/c-LLC) in an
      established pre-adipocyte cell line 3T3-L1 adipogenic capacity. c/c-LLC in the
      presence of 3T3-L1 caused a reduction in lipids accumulation, suggesting that
      secretory tumor cells products may affect adipogenesis. Interestingly, a very
      early (day 2) down-regulation of proliferator-activated receptor gamma
      (PPARgamma) and CCAAT/enhancer-binding protein alpha (C/EBPalpha), followed by
      late genes (day 4 and 8), adiponectin, perilipin, and fatty acid-binding protein
      4 (FABP4). Caspase-3 expression was increased on the last day of cell
      differentiation; it occurred in the expression of pro-inflammatory cytokines
      interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha). Overall, our
      results suggest that LLC secretory products impair adipocyte differentiation in a
      co-culture system and increased apoptosis. In summary, our study has shown the
      inhibition of the adipogenic process in the 3T3-L1 co-culture system with LLC
      cells.

PMID- 30094380
TI  - Chemical weathering in central Vietnam from clay mineralogy and major-element
      geochemistry of sedimentary rocks and river sediments.
AB  - Clay mineralogy and major-element geochemistry of Miocene sedimentary rock and
      modern river sediment samples collected from the Ba River basin in central
      Vietnam are used to evaluate the chemical weathering processes during the Miocene
      and the present time. The results show that Miocene andesitic sedimentary rocks
      consist of high smectite (average 72%) with moderate kaolinite (24%), while
      Miocene felsic sedimentary rocks display abundant kaolinite (65%) with moderate
      smectite (25%). In comparison, modern river sediments are characterized by
      moderate smectite (43%) and kaolinite (37%). The typical distribution of clay
      minerals in the Ba River basin can be resulted from abundant occurrence of felsic
      intrusive rocks and volcanic rocks along with weak tectonic uplift and the
      tropical East Asian monsoon climate during the Miocene and in the present time.
      Despite their different clay mineralogical compositions, major elements of these
      Miocene sedimentary rocks and modern river sediments display stronger depletion
      of Ca, Na and Mg than of K and Si during the chemical weathering. The chemical
      index of alteration (CIA) combined with kaolinite/illite ratio demonstrated
      moderate chemical weathering during the Miocene and in the present time in
      central Vietnam, demonstrating similar tectonic activity and climatic conditions
      occurred during these two periods.

PMID- 30094379
TI  - PIAS-family proteins negatively regulate Glis3 transactivation function through
      SUMO modification in pancreatic beta cells.
AB  - Gli-similar 3 (Glis3) is Kruppel-like transcription factor associated with the
      transcriptional regulation of insulin. Mutations within the Glis3 locus have been
      implicated in a number of pathologies including diabetes mellitus and
      hypothyroidism. Despite its clinical significance, little is known about the
      proteins and posttranslational modifications that regulate Glis3 transcriptional
      activity. In this report, we demonstrate that the SUMO-pathway associated
      proteins, PIASy and Ubc9 are capable of regulating Glis3 transactivation function
      through a SUMO-dependent mechanism. We present evidence that SUMOylation of Glis3
      by PIAS-family proteins occurs at two conserved lysine residues within the Glis3
      N-terminus and modification of Glis3 by SUMO dramatically inhibited insulin
      transcription. Finally, we provide evidence that Glis3 SUMOylation increases
      under conditions of chronically elevated glucose and correlates with decreased
      insulin transcription. Collectively, these results indicate that SUMOylation may
      serve as a mechanism to regulate Glis3 activity in beta cells.

PMID- 30094381
TI  - Educational attainment modifies the association of wealth status with elevated
      blood pressure in the Ghanaian population.
AB  - The relationship between wealth and blood pressure (BP) in developing countries
      is unclear and it is important to understand how the socioeconomic environment
      influences BP in an African setting. Our objective was to determine the wealth
      differences in BP in the Ghanaian population and to clarify whether the
      relationship is modified by education level. Data from the 2014 Ghana Demographic
      and Health Survey was analyzed. A total of 9396 women and 4388 men were sampled
      nationwide and interviewed for the survey. Prevalence of hypertension in the
      population was low (10.4%). Systolic BP, diastolic BP, and odds of elevated BP
      increased with increasing wealth status. A linear trend was noted. Richest
      respondents recorded a 2.65 mmHg (95% CI: 1.09, 4.21) and 3.14 mmHg (95% CI:
      1.97, 4.31) excess in systolic BP and diastolic BP, respectively and also, a 151%
      (AOR = 2.51, 95% CI: 1.80, 3.48) increased odds of elevated BP compared with the
      poorest. The wealth trend in BP was strongest among primary educated respondents
      (Interaction p = 0.0007). We found evidence of a consistent increase in elevated
      BP with increasing wealth status in this African population, a trend that is
      contrary to what is seen in high income countries.

PMID- 30094382
TI  - Corrigendum to "Removal of chromium (VI) from aqueous solution using vesicular
      basalt: A potential low cost wastewater treatment system" [Heliyon 4(7) (July
      2018), Article e00682].
AB  - [This corrects the article DOI: 10.1016/j.heliyon.2018.e00682.].

PMID- 30094383
TI  - The association between the perception of crime and walking in gated and non
      gated neighbourhoods of Asian developing countries.
AB  - It has been reported in the literature that the perception of crime at the
      neighbourhood level inversely affects the walking behaviour of individuals. On
      the other hand, the gated neighbourhoods are considered safe from crime, however,
      there is a lack of research on the association of the perception of crime and
      walking in gated neighbourhoods. Therefore, the objectives of the study reported
      in this paper were to investigate the association between the perception of crime
      and walking in gated and non-gated neighbourhoods. A questionnaire was used to
      collect the data on walking and the perception of crime in 16 neighbourhoods of
      Karachi Pakistan, 8 out of which were gated. Independent sample t-test and gamma
      tests were used for the data analysis. The results show that although there is a
      lower perception of crime in the gated neighbourhoods, yet the inhabitants of
      gated neighbourhoods engage in less physical activity comprising of walking. In
      spite of a greater perception of crime in non-gated neighbourhoods, higher values
      of walking were reported by the residents of those neighbourhoods. Therefore, it
      has been concluded that there does not exist a definite relationship between the
      perception of crime and walking behaviour at the neighbourhood level and the
      perceived safety from crime claimed by the proponents of the gated neighbourhoods
      does not encourage walking among the residents.

PMID- 30094384
TI  - The impact of trade with the United States on electric loads in Mexico.
AB  - We quantify the relationship between trade with the U.S. and electric loads in
      Mexico. Exports to the U.S. are highly statistically significant in explaining
      energy loads and significant in explaining peak loads, both in the presence and
      the absence of a deterministic trend in loads. These results support the
      hypothesis that trade impacts industrial load disproportionately. We conclude
      that a failure to renegotiate NAFTA is an important regulatory risk for buyers
      and sellers of electricity in Mexico. We offer an approach to adjusting forecasts
      accordingly.

PMID- 30094385
TI  - Laboratory-confirmed hospital-acquired infections: An analysis of a hospital's
      surveillance data in Nigeria.
AB  - Objective: Hospital-acquired infections (HAI) are a global problem and a major
      public health concern in hospitals throughout the world. Quantification of HAI is
      needed in developing countries; hence we describe the results of a 2-year
      surveillance data in a tertiary hospital in Nigeria. Methodology: This study is a
      2-year review using secondary data collected at a tertiary referral center in
      northwestern Nigeria. The data was collected using surveillance forms modeled
      based on the Centre for Disease Control (CDC) protocol. Descriptive statistics
      were used to present results as frequencies and percentages. Result: 518 patients
      developed HAI out of 8216 patients giving an overall prevalence of 6.3%. The mean
      age of the patients was 35.98 years (+/-15.92). Males constituted 281 (54.2%).
      UTI 223 (43.1%) was the most prevalent HAI. Overall, E. coli 207 (40.0%) was the
      most frequent isolates followed by P. aerugenosa 80 (15.4%). There was a high
      prevalence of cloxacillin resistant S. aureus (67.9%) and gram-negative rods
      resistant to third-generation cephalosporins. Trimethoprim-sulfamethoxazole
      resistance across the board was more than 90%. Conclusion: There is a high burden
      of HAI especially UTI in our hospital with resistance to commonly used
      antibiotics documented.

PMID- 30094387
TI  - Building clinical trials around patients: Evaluation and comparison of
      decentralized and conventional site models in patients with low back pain.
AB  - Clinical trials are slow and costly, built around the research centers that study
      local participants. Building clinical trials around patients in their homes and
      community through remote visits and monitoring could enhance recruitment and
      increase convenience for participants. This study evaluated different trial
      settings, a decentralized arm via telemedicine center (virtual study conduct), a
      conventional arm via health clinic (onsite study conduct) and a mixed model arm.
      Acute low-back pain patients (20-65 years) were recruited to this non
      interventional trial in Switzerland. The study consisted of a screening period
      and a 2-week data collection period using direct data capture (eSource),
      electronic informed consent form (eICF), electronic diary (eDiary) and wearable
      actigraphy sensor. A higher number of patients were enrolled in the decentralized
      arm (N = 18) compared to the conventional arm (N = 5) and none in the mixed model
      arm. The decentralized arm consisted of a diverse population with increased
      participation from rural areas. In the decentralized arm 89% of enrolled patients
      completed the study compared to 60% in the conventional arm. All the patients
      reported satisfaction with the use of eICF, eDiary and remote visits; whereas
      patients reported a lower level of satisfaction with the wearable sensor. The
      decentralized setting was operationally feasible and well accepted by patients.
      Faster recruitment and improved access to patients was observed in the
      decentralized arm. This study supports broader adoption of the decentralized
      model in clinical trials, though further investigations in larger interventional
      trials are needed to confirm the benefits from this patient-centric approach.

PMID- 30094386
TI  - Recruitment & retention program for the NeuroNEXT SMA Biomarker Study: Super
      Babies for SMA!
AB  - Background/Aims: Recruitment and retention of research participants are
      challenging and critical components of successful clinical trials and natural
      history studies. Infants with spinal muscular atrophy (SMA) have been a
      particularly challenging population to study due to their fragile and complex
      medical issues, poor prognosis and, until 2016, a lack of effective therapies.
      Recruitment of healthy infants into clinical trials and natural history studies
      is also challenging and sometimes assumed to not be feasible. Methods: In 2011,
      our group initiated a two-year, longitudinal natural history study of infants
      with SMA and healthy infant controls to provide data to assist in the analysis
      and interpretation of planned clinical trials in infants with SMA. The
      recruitment goal was to enroll 27 infants less than 6 months of age with SMA and
      27 age-matched healthy infants within the two-year enrollment period. A detailed
      recruitment and retention plan was developed for this purpose. In addition, a
      survey was administered to participant families to understand the determinants of
      participation in the study. Results: All healthy infants were recruited within
      the study's first year and 26 SMA infants were recruited within the two-year
      recruitment period. Thirty-eight participant families responded to the
      recruitment determinants survey. Nearly half of respondents (18/38, 48%) reported
      that they first heard of the study from their physician or neurologist. The most
      common reason to decide to enroll their infant (22/38, 58%) and to remain in the
      study (28/38, 74%) was their understanding of the importance of the study.
      Thematic recruitment tools such as a study brochure, video on social media, and
      presentations at advocacy meetings were reported to positively influence the
      decision to enroll. Conclusions: A proactive, thematic and inclusive recruitment
      and retention plan that effectively communicates the rationale of a clinical
      study and partners with patients, advocacy groups and the local communities can
      effectively recruit participants in vulnerable populations. Recommendations for
      the proactive integration of recruitment and retention plans into clinical trial
      protocol development are provided.

PMID- 30094389
TI  - Physical Activity and Community Engagement (PACE) to facilitate community
      reintegration among returning veterans: Study protocol for a randomized
      controlled trial.
AB  - There is a surprising lack of disseminable, community-based interventions for
      veterans experiencing difficulties during the reintegration process from military
      to civilian life. Physical Activity and Community Engagement (PACE) is a program
      which combines routine vigorous-intensity exercise with community engagement. The
      program builds on emergent evidence supporting the benefits of routine vigorous
      intensity exercise among and establishing social connection. Using a randomized
      controlled trial (N = 60), we will obtain feasibility data and initial effect
      sizes for the early effects of PACE on reintegration difficulties.

PMID- 30094388
TI  - Harmonization, data management, and statistical issues related to prospective
      multicenter studies in Ankylosing spondylitis (AS): Experience from the
      Prospective Study Of Ankylosing Spondylitis (PSOAS) cohort.
AB  - Ankylosing spondylitis (AS) is characterized by inflammation of the spine and
      sacroiliac joints causing pain and stiffness and, in some patients, ultimately
      new bone formation, and progressive joint ankyloses. The classical definition of
      AS is based on the modified New York (mNY) criteria. Limited data have been
      reported regarding data quality assurance procedure for multicenter or multisite
      prospective cohort of patients with AS. Since 2002, 1272 qualified AS patients
      have been enrolled from five sites (4 US sites and 1 Australian site) in the
      Prospective Study Of Ankylosing Spondylitis (PSOAS). In 2012, a Data Management
      and Statistical Core (DMSC) was added to the PSOAS team to assist in study
      design, establish a systematic approach to data management and data quality, and
      develop and apply appropriate statistical analysis of data. With assistance from
      the PSOAS investigators, DMSC modified Case Report Forms and developed database
      in Research Electronic Data Capture (REDCap). DMSC also developed additional data
      quality assurance procedure to assure data quality. The error rate for various
      forms in PSOAS databases ranged from 0.07% for medications data to 1.1% for
      arthritis activity questionnaire-Global pain. Furthermore, based on data from a
      sub study of 48 patients with AS, we showed a strong level (90.0%) of agreement
      between the two readers of X-rays with respect to modified Stoke Ankylosing
      Spondylitis Spine Score (mSASSS). This paper not only could serve as reference
      for future publications from PSOAS cohort but also could serve as a basic guide
      to ensuring data quality for multicenter clinical studies.

PMID- 30094391
TI  - A case of bilateral vasculitis associated with pineal germinoma.
AB  - Purpose: To report a rare case of bilateral periphlebitis associated with a
      pineal germinoma. Observations: A 17-year-old male teenager presented at a local
      clinic complaining of blurred vision in both eyes. The treating physician
      identified bilateral uveitis, and prescribed the patient with a local steroid
      treatment. However, the inflammatory findings did not improve with the treatment,
      and the patient was referred to our hospital for further examination. At the
      first visit, his best-corrected visual acuities were 0.3 for the right eye and
      0.06 for the left eye; we found no inflammation in the anterior ocular segment,
      but observed bilateral retinal periphlebitis and a proliferative membrane from
      the papilla to the macula in the ocular fundus. In addition, we found a
      tractional serous retinal detachment in the macula. We suspected tuberculous
      uveitis clinically and initiated treatment with an antituberculous drug. However,
      the condition of the patient did not improve. Two months after our initial
      examination, left optic neuritis appeared, and we initiated a steroid pulse
      therapy. Although the periphlebitis remained, the left optic nerve findings and
      the visual acuity of both eyes improved. Thus, we reduced the oral steroid dose
      gradually. However, two months after initiating the dose reduction, the patient
      suffered a consciousness disturbance, and we detected a pineal tumor by magnetic
      resonance imaging (MRI). The patient was diagnosed as having a germ cell tumor by
      pathological examination and underwent radiation and chemotherapy. We noted
      marked improvements in both the periphlebitis findings and in the visual acuity
      following the treatment for the pineal tumor. Conclusions and importance: Cases
      of pineal tumor accompanied with retinal periphlebitis have been reported rarely.
      Because juvenile retinal vasculitis cases of unknown cause can be associated with
      pineal germinomas, we recommend brain MRI examinations for such cases.

PMID- 30094390
TI  - An analysis of adaptations to multi-level intervention strategies to enhance
      implementation of clinical practice guidelines for treating tobacco use in dental
      care settings.
AB  - Introduction: Our team conducted a cluster randomized controlled trial (DUET)
      that compared the effectiveness of three theory-driven, implementation strategies
      on dental provider adherence to tobacco dependence treatment guidelines (TDT). In
      this paper we describe the process of adapting the implementation strategies to
      the local context of participating dental public health clinics in New York City.
      Methods: Eighteen dental clinics were randomized to one of three study arms
      testing several implementation strategies: Current Best Practices (CBP) (i.e.
      staff training, clinical reminder system and Quitline referral system); CBP +
      Performance Feedback (PF) (i.e. feedback reports on provider delivery of TDT);
      and CBP + PF + Pay-for-Performance (i.e. financial incentives for provision of
      TDT). Through an iterative process, we used Stirman's modification framework to
      classify, code and analyze modifications made to the implementation strategies.
      Results: We identified examples of six of Stirman's twelve content modification
      categories and two of the four context modification categories. Content
      modifications were classified as: tailoring, tweaking or refining (49.8%), adding
      elements (14.1%), departing from the intervention (9.3%), loosening structure
      (4.4%), lengthening and extending (4.4%) and substituting elements (4.4%).
      Context modifications were classified as those related to personnel (7.9%) and to
      the format/channel (8.8%) of the intervention delivery. Common factors associated
      with adaptations that arose during the intervention included staff changes, time
      constraints, changes in leadership preferences and functional limitations of to
      the Electronic Dental Record. Conclusions: This study offers guidance on how to
      capture intervention adaptation in the context of a multi-level intervention
      aimed at implementing sustainable changes to optimize TDT in varying public
      health dental settings.

PMID- 30094393
TI  - Amalric triangular sign in a case of central retinal artery occlusion combined
      with posterior ciliary artery occlusion - Case report.
AB  - Purpose: Amalric triangular sign is a rare phenomenon indicating choroidal
      ischemia. In this study, we reported a typical Amalric triangular sign in a case
      of central retinal artery occlusion (CRAO) combined with posterior ciliary artery
      (PCA) occlusion. Observations: A 49-year-old women developed sudden visual loss
      in her left eye for one day. Ocular examination revealed rubeosis iridis, macular
      retinal edema followed by multiple whitish triangular patches in the peripheral
      four days later. Fluorescein angiography (FAG) revealed delayed choroidal filling
      time, delayed arteriovenous transit time, choroidal non-perfusion areas and
      triangular lesions of hyperfluorescent corresponding to the hypopigmented patches
      on the fundus. Carotid Doppler and magnetic resonance angiography (MRA) then
      disclosed 90% stenosis of left internal carotid artery (ICA), causing ischemia of
      the central retinal artery and posterior ciliary artery. Conclusions and
      importance: The Amalric triangular sign indicates the occlusion on the main truck
      of PCA. The sign might combine with CRAO or branch retinal artery occlusion
      (BRAO) as presented in our case and therefore is a strong indication of possible
      systemic vascular risk.

PMID- 30094392
TI  - Molecular diagnosis and ocular imaging of varicella zoster virus associated
      neuroretinitis.
AB  - Purpose: To report a case of varicella zoster virus associated neuroretinitis
      confirmed via polymerase chain reaction analysis of ocular fluid. Observations: A
      30-year-old man presented with a 1-week history of decreased vision in his left
      eye and ulcerative skin lesions above his left eyebrow. On exam, he had clinical
      findings consistent with neuroretinitis characterized by optic disc edema and
      formation of a macular star. Polymerase chain reaction analysis of aqueous fluid
      was positive for varicella zoster virus. He was treated with oral valacyclovir
      with excellent resolution of his symptoms and clinical findings. Conclusions and
      importance: Varicella zoster virus is a rare cause of neuroretinitis. We report
      for the first time a case of varicella zoster virus associated neuroretinitis
      confirmed by polymerase chain reaction analysis of ocular fluid. Molecular
      testing of ocular tissue may lead to a definitive diagnosis.

PMID- 30094394
TI  - Advanced coats-like retinopathy as the initial presentation of Familial Retinal
      Arterial Macroaneurysms.
AB  - Purpose: To describe two young Saudi brothers with bilateral progressive retinal
      arterial aneurysms and a subtotal exudative retinal detachment with Coats-like
      presentation in the older sibling as the initial presentation of Familial Retinal
      Arterial Macroaneurysms (FRAM). Observations: Two young Saudi brothers with a
      family history of consanguinity presented with the classic clinical presentation
      and genetic identification of FRAM. In this report, we describe the presence of
      prominent peripheral retinal capillary changes mimicking Coats' disease.
      Conclusions and importance: FRAM can present similar to bilateral Coats' disease
      and should be considered in the differential diagnosis of Coats-like retinopathy.
      The diagnosis of FRAM may have a significant implication because of the
      associated cardiac abnormality, such as supravalvular pulmonary stenosis, which
      should be evaluated by echocardiography and managed accordingly.

PMID- 30094395
TI  - Orbital and chorioretinal manifestations of Erdheim-Chester disease treated with
      vemurafenib.
AB  - Purpose: We report a patient with severe multi-organ dysfunction of unknown
      origin who presented with bilateral orbital and chorioretinal manifestations that
      led to the diagnosis of Erdheim-Chester Disease (ECD). Observations: ECD is a
      rare, histiocytic, proliferative disorder characterized by multi-systemic organ
      involvement that has historically lacked effective therapy. Our patient underwent
      genetic testing that was positive for the BRAF V600E mutation; therefore, the
      patient was treated with vemurafenib. Conclusions and importance: This case
      demonstrates the rare orbital and intraocular manifestations of ECD and the
      unfortunate impact of a delayed diagnosis, the importance of early gene therapy
      testing for management decisions, and the utilization of targeted directed
      therapy to improve visual outcomes and quality of life.

PMID- 30094396
TI  - Fibrous histiocytoma as first presentation in systemic lupus erythematosus and
      sero-positive Sjogren's syndrome.
AB  - Purpose: To describe a triad of fibrous histiocytoma, Systemic Lupus
      Erythematosus and Sero-positive Sjogren's Syndrome. Observations: This case was
      diagnosed first as bilateral fibrous histiocytoma of cheeks, which on further
      investigations proved to be a triad of Systemic Lupus Erythematosus, Fibrous
      histiocytoma and Sero-positive Sjogren's Syndrome. Conclusions and importance:
      Association between fibrous histiocytoma, Systemic Lupus Erythematosus and Sero
      positive Sjogren's Syndrome has been known before, but fibrous histiocytoma as
      first presentation in the triad has not been reported.

PMID- 30094397
TI  - Bilateral BrightOcular iris implants necessitating explantation and subsequent
      endothelial keratoplasty.
AB  - Purpose: To demonstrate the dangers associated with the BrightOcular iris
      implant, a model that had initially been touted as safer than its predecessors.
      Observations: A 41-year-old male presented with decreased vision in both eyes,
      approximately two years following bilateral BrightOcular cosmetic iris
      implantation performed in Mexico. On initial consultation, he was found to have
      bilateral corneal decompensation with stromal edema and a significantly reduced
      endothelial cell count (ECC). On follow up 5 weeks later, his vision and corneal
      edema had further detriorated. In the following month, he underwent explantation
      of the cosmetic iris implants in both eyes. Significant corneal edema persisted
      in the right eye several months post-operatively, to the point of necessitating
      endothelial keratoplasty. Conclusions and importance: Despite numerous reports in
      the literature of the significant ocular complications that can arise secondary
      to cosmetic iris implantation, individuals continue to willingly undergo this
      surgery. Our intention with presenting this case to the ophthalmologic community
      is two-fold: to highlight the ongoing clinical risk that BrightOcular devices
      pose, despite being marketed as safer than the older NewColourIris models, and to
      stress the urgency with which cosmetic iris implants should be removed from the
      eye.

PMID- 30094398
TI  - Sydney Chung.

PMID- 30094399
TI  - Association of Hepatic Steatosis With Subclinical Atherosclerosis: Systematic
      Review and Meta-Analysis.
AB  - Nonalcoholic fatty liver disease (NAFLD) is becoming common in the United States
      and throughout the world and can progress to cirrhosis, hepatocellular carcinoma,
      and death. There is a strong association between coronary artery disease and
      NAFLD due to common risk factors, such as metabolic syndrome, obesity, and
      diabetes mellitus. Subclinical atherosclerosis, defined as coronary artery
      calcification in asymptomatic patients, has been shown to have a higher incidence
      in patients with NAFLD. We performed a meta-analysis to examine the association
      of NAFLD with subclinical atherosclerosis measured by coronary artery calcium
      (CAC) scoring. Data were extracted from 12 studies selected using a predefined
      search strategy. NAFLD was diagnosed by abdominal ultrasound or computed
      tomography scans. The rate of coronary artery calcification was analyzed using
      random effects models, and publication bias was assessed using Egger's regression
      test. A total of 42,410 subjects were assessed, including 16,883 patients with
      NAFLD. Mean CAC score was significantly higher in subjects with NAFLD compared to
      those without NAFLD (odds ratio with random effects model, 1.64; 95% confidence
      inteval, 1.42-1.89). This association remained significant through subgroup
      analyses for studies with >1,000 subjects and a higher CAC score cutoff of >100.
      Higher aspartate aminotransferase levels were also associated with increased
      subclinical atherosclerosis (mean difference 1.77; 95% confidence interval, 1.19
      2.34). Conclusion: There is an increased prevalence of subclinical
      atherosclerosis in patients with NAFLD, where subclinical atherosclerosis is
      defined using a "real world" clinical biomarker, namely the CAC score.
      Prospective studies are needed to establish a causative link between NAFLD and
      coronary artery disease. (Hepatology Communications 2018; 00:000-000).

PMID- 30094400
TI  - Liver Fibrosis Is Associated With Corrected QT Prolongation During
      Ledipasvir/Sofosbuvir Treatment for Patients With Chronic Hepatitis C.
AB  - Combination treatment of ledipasvir and sofosbuvir (LDV/SOF) is first-line
      treatment for patients with chronic hepatitis C genotype 1 in the United States,
      Europe, and Japan. However, the influence of LDV/SOF on the cardiovascular system
      is poorly characterized. A total of 470 chronic hepatitis C patients who started
      LDV/SOF treatment between September 2015 and February 2016 at nine hospitals in
      Japan were prospectively enrolled in this study. Corrected QT (QTc) prolongation
      was defined as a QTc interval >=450 milliseconds. The sustained virologic
      response rate was 96.0% (451/470), and the discontinuance rate due to adverse
      effects was 0.9% (4/470). Among 395 patients whose electrocardiogram was
      evaluated over time and compared with baseline, the QTc interval was
      significantly prolonged during treatment and returned to baseline levels 12 weeks
      after the end of treatment. Twenty-four of 376 patients with baseline QTc
      intervals <450 milliseconds experienced on-treatment QTc prolongation. Higher
      aspartate aminotransferase-to-platelet ratio index scores (>=0.76; odds ratio,
      4.375; P = 0.005) and longer QTc intervals (>=416 milliseconds; odds ratio,
      4.823; P = 0.003) at baseline were significantly associated with on-treatment QTc
      prolongation on multivariate analysis. Patients with cirrhosis showed
      significantly longer QTc intervals than those without cirrhosis during treatment
      but not at baseline, and they developed on-treatment QTc prolongation at a higher
      rate than patients without cirrhosis. No cardiovascular events occurred, except
      for 1 patient who developed paroxysmal supraventricular tachycardia. Conclusion:
      Newly developed QTc prolongation was observed in 6.4% of Japanese patients during
      treatment and was associated with more advanced fibrosis. (Hepatology
      Communications 2018; 00:000-000).

PMID- 30094402
TI  - L-Carnitine Suppresses Loss of Skeletal Muscle Mass in Patients With Liver
      Cirrhosis.
AB  - Liver cirrhosis (LC) is a major cause of secondary sarcopenia. Sarcopenia makes
      the prognosis worse; thus, novel therapeutic options for sarcopenia in patients
      with LC are urgently required as they are currently limited. In this
      retrospective study, 158 patients with LC were screened, and 35 of those patients
      who were treated with L-carnitine for more than 6 months and for whom skeletal
      muscle mass changes could be evaluated by computer tomography were enrolled. Of
      the 158 patients, 79 patients who did not receive L-carnitine supplementation
      served as controls. Cases and controls were propensity score matched for age,
      sex, presence of hepatocellular carcinoma, and branched chain amino acid
      administration, and changes in skeletal muscle mass and clinical data were
      compared. The 35 patients who received L-carnitine supplementation and 35
      propensity score-matched patients who did not receive carnitine supplementation
      comprised the final enrollment. Compared with control patients, patients who
      received L-carnitine had significantly worse liver function, which is associated
      with rapid progress of skeletal muscle depletion. However, loss of skeletal
      muscle mass was significantly suppressed in patients receiving L-carnitine, and a
      significant effect was observed in patient subgroups stratified by age, sex,
      presence of hepatocellular carcinoma, and branched chain amino acid
      administration. The change ratios of most laboratory data, including vitamin D
      and insulin-like growth factor 1 levels, were similar in the two groups, but
      ammonia levels were significantly less in those receiving L-carnitine. However,
      even in patients receiving L-carnitine but not showing an ammonia decrease, loss
      of skeletal muscle was significantly suppressed. Conclusion: L-carnitine
      suppresses loss of skeletal muscle mass and may therefore be a novel therapeutic
      option for sarcopenia in patients with LC. (Hepatology Communications 2018;
      00:000-000).

PMID- 30094401
TI  - A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease
      With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary
      Care.
AB  - Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score
      [NFS], fibrosis 4 score [FIB-4], or enhanced liver fibrosis [ELF] test) are
      recommended as first-line tools to determine the risk of advanced fibrosis in
      nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic
      approach to screening for clinically significant fibrosis in primary care and
      diabetes clinics. We recruited 252 patients from an endocrine clinic or primary
      care facility. Anthropometric measurements, ELF test, ultrasound, and liver
      stiffness measurements (LSMs) were performed. Clinically significant fibrosis was
      defined as LSM >=8.2 kPa or ELF >=9.8. A subgroup of patients underwent liver
      biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were
      57.3 +/- 12.3 years old with a high prevalence of metabolic syndrome (84.5%),
      type 2 diabetes (82.5%), and body mass index (BMI) >=40 kg/m2 (21.8%). LSM met
      quality criteria in 230 (91.3%) patients. NFS and FIB-4 combined had a high
      negative predictive value (90.0%) for excluding LSM >=8.2 kPa. However, 84.1% of
      patients had indeterminate or high NFS or FIB-4 scores requiring further
      assessment. LSM >=8.2 kPa and ELF >=9.8 were present in 31.3% and 28.6% of
      patients, respectively. Following adjustment for age, BMI, sex, and presence of
      advanced fibrosis, older age was independently associated with ELF >=9.8
      (adjusted odds ratio, 1.14; 95% confidence interval, 1.06-1.24), whereas
      increasing BMI was independently associated with LSM >=8.2 kPa (adjusted odds
      ratio, 1.15; 95% confidence interval, 1.01-1.30). Concordant LSM <8.2 kPa and ELF
      <9.8 and concordant LSM >=8.2 kPa and ELF >=9.8 had a high negative predictive
      value (91.7%) and positive predictive value (95.8%) for excluding and identifying
      clinically significant fibrosis, respectively. Conclusion: Simple scoring tools
      alone lack accuracy. LSM accuracy is influenced by severe obesity, whereas age
      impacts the ELF test. Further studies are required to confirm whether combining
      LSM and ELF may enhance accuracy and confidence in identifying clinically
      significant fibrosis. (Hepatology Communications 2018; 00:000-000).

PMID- 30094403
TI  - Spleen and Liver Volumetrics as Surrogate Markers of Hepatic Venous Pressure
      Gradient in Patients With Noncirrhotic Portal Hypertension.
AB  - Noncirrhotic portal hypertension (NCPH) is a rare disease that may lead to
      serious clinical consequences. Currently, noninvasive tools for the assessment of
      NCPH are absent. We investigated the utility of spleen and liver volumetrics as a
      marker of the presence and severity of portal hypertension in this population. A
      cohort of NCPH patients evaluated between 2003 and 2015 was retrospectively
      studied. The association of spleen and liver volumes with the hepatic venous
      pressure gradient (HVPG) level was evaluated using locally weighted scatterplot
      smoothing curves. A cohort of patients with viral hepatitis-related liver disease
      was used as controls. Of the 86 patients with NCPH evaluated during the study
      period, 75 (mean age, 35 +/- 17; 73% males) were included in the final analysis.
      Patients with portal hypertension had significantly higher spleen and liver to
      body mass index (BMI) ratios compared to patients with HVPG <5 mm Hg (39.5 +/-
      27.9 versus 22.8 +/- 10.6 cm3/kg/m2, P = 0.003; 91.1 +/- 40.1 versus 71.4 +/-
      16.7 cm3/kg/m2, P = 0.014, for spleen/BMI and liver/BMI, respectively). In
      contrast to the patients with viral hepatitis, a positive linear correlation was
      observed in the NCPH cohort between spleen/BMI and liver/BMI (above a cutoff of
      25 and 80 cm3/kg/m2, respectively) and HVPG level. Additionally, only in the NCPH
      cohort was an increase in spleen/BMI range quartile predictive of a higher
      prevalence of portal hypertension and clinically significant portal hypertension
      (trend, P = 0.014 and 0.031, respectively). Conclusion: Spleen and liver
      volumetrics may have utility in the assessment of NCPH as a noninvasive biomarker
      that can be performed using routine radiologic examinations. Further studies are
      needed to validate these findings. (Hepatology Communications 2018; 00:000-000).

PMID- 30094404
TI  - Prognostic Significance of Controlled Attenuation Parameter in Patients With
      Compensated Advanced Chronic Liver Disease.
AB  - Obesity and steatosis have been associated with liver disease progression in
      patients with compensated advanced chronic liver disease (cACLD) (liver stiffness
      measurement [LSM] >= 10 kPa). The controlled attenuation parameter (CAP)
      estimates steatosis during LSM by transient elastography. We aimed to evaluate
      whether CAP is associated with the development of clinically relevant events in
      cACLD. Consecutive patients with cACLD and CAP measurements observed between
      September 2013 and September 2015 were retrospectively studied. Classical
      decompensation and severe bacterial infections on follow-up were recorded. A
      predefined CAP cut-off for steatosis was used (220 dB/m; 90% sensitivity). The
      association among LSM, CAP, and events was assessed by univariate and
      multivariate Cox regression. Among the 193 patients (viral etiology = 58%; median
      Child score = 5; LSM = 15.1 kPa; CAP = 255 +/- 62 dB/m) who were followed up in
      median for 18 months, 18 developed clinically relevant events (11 liver
      decompensation, 7 severe bacterial infections). Patients developing events had
      higher LSM (median: 30.8 versus 14.3 kPa, P < 0.001) and showed trends for higher
      CAP (275 +/- 46 versus 252 +/- 63 dB/m, P = 0.07), lower platelet count (134 +/-
      74 versus 167 +/- 74 G/L, P = 0.07), and worse liver function versus patients
      remaining compensated. Body mass index was similar in the two groups. All events
      were more frequent in patients with CAP being greater than or equal to 220 dB/m
      (12.9% versus 1.6% in CAP < 220; P = 0.013), and 10 of 11 episodes of liver
      decompensation occurred in patients with CAP being greater than or equal to 220
      dB/m. Following multivariate analysis, LSM and CAP greater than or equal to 220
      dB/m remained independently associated with clinical events in the whole
      population and in patients with clinically significant portal hypertension.
      Conclusion: The CAP being greater than or equal to 220 dB/m is associated with
      increased risk of clinical decompensation and bacterial infections independent of
      LSM in patients with cACLD and allows refining the noninvasive risk
      stratification in this population. (Hepatology Communications 2018; 00:000-000).

PMID- 30094405
TI  - A Survey of Molecular Heterogeneity in Hepatocellular Carcinoma.
AB  - Understanding the heterogeneity of dysregulated pathways associated with the
      development of hepatocellular carcinoma (HCC) may provide prognostic and
      therapeutic avenues for disease management. As HCC involves a complex process of
      genetic and epigenetic modifications, we evaluated expression of both
      polyadenylated transcripts and microRNAs from HCC and liver samples derived from
      two cohorts of patients undergoing either partial hepatic resection or liver
      transplantation. Copy number variants were inferred from whole genome low-pass
      sequencing data, and a set of 56 cancer-related genes were screened using an
      oncology panel assay. HCC was associated with marked transcriptional deregulation
      of hundreds of protein-coding genes. In the partially resected livers, diminished
      transcriptional activity was observed in genes associated with drug catabolism
      and increased expression in genes related to inflammatory responses and cell
      proliferation. Moreover, several long noncoding RNAs and microRNAs not previously
      linked with HCC were found to be deregulated. In liver transplant recipients,
      down-regulation of genes involved in energy production and up-regulation of genes
      associated with glycolysis were detected. Numerous copy number variants events
      were observed, with hotspots on chromosomes 1 and 17. Amplifications were more
      common than deletions and spanned regions containing genes potentially involved
      in tumorigenesis. Colony stimulating factor 1 receptor (CSF1R), fibroblast growth
      factor receptor 3 (FGFR3), fms-like tyrosine kinase 3 (FLT3), nucleolar
      phosphoprotein B23 (NPM1), platelet-derived growth factor receptor alpha
      polypeptide (PDGFRA), phosphatase and tensin homolog (PTEN), G-protein-coupled
      receptors-like receptor Smoothened (SMO), and tumor protein P53 (TP53) were
      mutated in all tumors; another 26 cancer-related genes were mutated with variable
      penetrance. Conclusion: Our results underscore the marked molecular heterogeneity
      between HCC tumors and reinforce the notion that precision medicine approaches
      are needed for management of individual HCC. These data will serve as a resource
      to generate hypotheses for further research to improve our understanding of HCC
      biology. (Hepatology Communications 2018; 00:000-000).

PMID- 30094406
TI  - Gut and Liver B Cells of Common Clonal Origin in Primary Sclerosing Cholangitis
      Inflammatory Bowel Disease.
AB  - B cells express an antigen-specific B-cell receptor (BCR) and may contribute to
      liver inflammation by recognizing shared antigens in the gut and liver. Herein,
      we used high-throughput BCR sequencing of the immunoglobulin heavy chain,
      specifically the complementarity-determining region 3 (CDR3), to characterize the
      B-cell repertoire of freshly-frozen paired gut and liver tissue samples from
      patients with primary sclerosing cholangitis (PSC) and concurrent inflammatory
      bowel disease (IBD) (PSC-IBD, n = 10) and paired formalin-fixed paraffin-embedded
      (FFPE) tumor-adjacent normal colon and liver tissue from patients with colorectal
      liver metastases (controls, n = 10). We observed significantly greater numbers of
      B cells (P < 0.01) and unique B-cell clonotypes (P < 0.05) in gut samples
      compared to liver samples of patients with PSC-IBD, whereas BCR sequences in FFPE
      normal gut and liver samples were nearly absent (14 +/- 5 clonotypes; mean +/-
      SD; n = 20). In PSC-IBD, an average of 8.3% (range, 1.6%-18.0%) of B-cell
      clonotypes were found to overlap paired gut and liver samples following the
      exclusion of memory clonotypes reported in the blood of healthy controls.
      Overlapping gut and liver clonotypes showed stronger evidence of antigen-driven
      activation compared to non-overlapping clonotypes, including shorter CDR3 lengths
      and higher counts of somatic hypermutation (P < 0.0001). Conclusion: A proportion
      of gut and liver B cells originate from a common clonal origin (i.e., likely to
      recognize the same antigen) in patients with PSC which suggests B-cell antigens
      are shared across the gut-liver axis. (Hepatology Communications 2018; 00:000
      000).

PMID- 30094407
TI  - Immune Alterations in Patients With Type 1 Autoimmune Hepatitis Persist Upon
      Standard Immunosuppressive Treatment.
AB  - Autoimmune hepatitis (AIH) is a rare disease characterized by an immune attack of
      the liver. This study consists of a comprehensive analysis of immune alterations
      related to AIH at diagnosis, and during remission phase under treatment. A total
      of 37 major lymphocyte populations were analyzed from the peripheral blood of new
      onset AIH patients (AIHn; n = 14), AIH patients with controlled disease (n = 11),
      and healthy subjects (n = 14). Liver biopsy analyses were performed to complete
      the blood phenotypic analysis. Four blood lymphocyte populations were
      significantly altered in AIHn patients at diagnosis compared with healthy
      subjects. Levels of mucosal-associated invariant T cells (MAIT), Type 1/Type 17
      helper (Th1/ Th17) cells, clusters of differentiation (CD4) T cells, and
      invariant natural killer T cells were decreased, whereas MAIT granzyme B+ (GrB)
      cells were increased. A trend toward an increase of CD8+CD161+GrB+ cells was also
      observed. These alterations were not restored with standard immunosuppressive
      treatments. In the liver of AIHn patients, CD4, forkhead box P3 (Foxp3), and MAIT
      cell markers were enriched in the portal tract, and CD8, CD161, and GrB markers
      were enriched in the hepatic lobule. During remission, the hepatic lobule was
      clear of infiltrating T cells, but residual CD4 and MAIT cells were found in the
      portal tract, where Foxp3 was decreased, as previously described. In vitro, MAIT
      cells were functionally altered in AIH patients. Ex vivo MAIT cell activity (GrB)
      was linked to severe fibrosis. Conclusion: Our work proposes a global view of the
      lymphocyte alterations from diagnosis to remission phase in AIH patients. The
      absence of blood immune homeostasis restoration and the persistence of a CD4
      infiltrate in the liver under standard immunosuppression could form the basis of
      the high risk of relapse observed in AIH. (Hepatology Communications 2018; 00:000
      000).

PMID- 30094408
TI  - "I Miss My Liver." Nonmedical Sources in the History of Hepatocentrism.
AB  - Hepatocentrism was a medical doctrine that considered the liver the center of the
      whole human being. It originated in ancient populations (Mesopotamic
      civilization) and persisted in Western countries until the seventeenth century.
      Hidden references to hepatocentrism may be found in artistic representations and
      literary works, from the myth of Prometheus in the Greco-Roman world to the
      crucifixion iconography throughout the Middle Ages. In the mid-1600s, fundamental
      discoveries irrefutably demonstrated the central role of the heart in human
      physiology, which laid the foundations for creating cardiocentrism, shifting the
      life's center from the liver to the heart. The advent of cardiocentrism
      immediately restricted the importance given to the liver, favoring the heart in
      the fine arts. Nevertheless, the liver maintained its importance in literature
      and popular belief as is evidenced by the widely acclaimed literary texts "Snow
      White" by the Brothers Grimm, "Moby Dick" by Herman Melville, and "Ode to the
      Liver" by Pablo Neruda. Our aim is to analyze the most significant artistic
      representations and literary works that contain references to hepatocentrism,
      evaluating the changing ideas and beliefs regarding the role and function of the
      liver throughout history. We want to underline the tight relationship between art
      and medicine; fine art and literature could be a valuable source for
      understanding the history of hepatology. (Hepatology Communications 2018; 00:000
      000).

PMID- 30094410
TI  - Does Sex Bias Play a Role for Dissatisfied Patients With Hypothyroidism?
AB  - The current state of the diagnosis and management of thyroid disease cannot be
      separated from the larger context of women's health for the following reasons:
      (1) the disproportionate incidence and prevalence of functional and structural
      thyroid diseases among women vs men; (2) the role of thyroid health on fertility,
      pregnancy, and postpartum; and (3) the challenge posed in managing the
      nonspecific symptoms of functional thyroid disease in the context of menopause.
      Here, we explore the hypothesis that sex bias has played a role in the management
      of thyroid diseases historically and has extended into the modern medical era.
      Once knowledge gaps that may have resulted from sex bias are recognized, we can
      strive to overcome this bias and develop better treatments to improve patient
      outcomes universally.

PMID- 30094409
TI  - Serum IL-1 Receptor Antagonist Concentrations Associate With Unfavorable
      Metabolic Features in 12-Year-Old Children.
AB  - Context: Elevated IL-1 receptor antagonist (IL-1Ra) concentrations are associated
      with obesity, insulin resistance, and cardiovascular disease (CVD) risk in
      adults. Objective: To determine if serum IL-1Ra and high-sensitivity C-reactive
      protein (hs-CRP) levels are associated with markers of reduced insulin
      sensitivity (IS) and serum lipids in 12-year-old children. Design and
      Participants: Of 191 children (n = 109 girls), 78 were categorized as having had
      birth weight and length appropriate for gestational age (AGA), 69 were small for
      gestational age, and 44 were AGA and from preeclamptic pregnancies. Serum markers
      of low-grade inflammation, IS, and lipids were measured. Quantitative Insulin
      Sensitivity Check Index (QUICKI) was calculated. Results: Mean serum IL-1Ra
      levels did not differ between the sexes or among the gestational categories.
      Children in the highest IL-1Ra tertile had lower QUICKI, IGF-binding protein-1,
      SHBG, and high-density lipoprotein cholesterol values; and higher body mass index
      (BMI), waist circumference to height ratio (WHtR), and serum insulin, hs-CRP,
      leptin, and triglyceride concentrations than those in the lowest IL-1Ra tertile.
      Logistic regression analysis showed higher serum hs-CRP and leptin levels, and
      WHtR were associated with high serum IL-1Ra levels. IL-1Ra concentration could be
      used to discriminate the children with lowest IS (area under the curve, 0.68; P <
      0.001); hs-CRP level could not. Conclusion: Children with the highest IL-1Ra
      levels had lower IS, higher hs-CRP levels and BMI, and a less favorable lipid
      profile than those with the lowest IL-1Ra levels, suggesting that high IL-1Ra
      concentrations may be associated with increased CVD risk in 12-year-old children.

PMID- 30094413
TI  - Acute Abdomen with Periumbilical Erythema.
AB  - A 33-year-old man with a history of a Malone Antegrade Continence Enema Procedure
      presented to the Emergency Department with right lower abdominal pain. Computed
      Tomography (CT) of the abdomen revealed an appendicitis of the appendicostomy
      with an associated appendicolith.

PMID- 30094412
TI  - Targeting the HGF/MET Axis Counters Primary Resistance to KIT Inhibition in KIT
      Mutant Melanoma.

PMID- 30094411
TI  - GC/MS in Recent Years Has Defined the Normal and Clinically Disordered
      Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?
AB  - Gas chromatography/mass spectrometry (GC/MS) has been used for steroid analysis
      since the 1960s. The advent of protective derivatization, capillary columns, and
      inexpensive electron ionization bench-top single quadrupole soon made it the
      method of choice for studying disorders of steroid synthesis and metabolism.
      However, the lengthy sample workup prevented GC/MS from becoming routine for
      steroid hormone measurement, which was dominated by radioimmunoassay. It was the
      emergence of liquid chromatography/tandem MS (LC/MS/MS) that sparked a renewed
      interest in GC/MS for the multicomponent analysis of steroids. GC/MS is excellent
      at providing an integrated picture of a person's steroid metabolome, or
      steroidome, as we term it. We review the recent work on newly described disorders
      and discuss the technical advances such as GC coupling to triple quadrupole and
      ion trap analyzers, two-dimensional GC/MS, and alternative ionization and
      detection systems such as atmospheric pressure chemical ionization (APCI) and
      time of flight. We believe that no novel GC/MS-based technique has the power of
      GC(electron ionization)/MS/MS as a "discovery tool," although APCI might provide
      ultimate sensitivity, which might be required in tissue steroidomics. Finally, we
      discuss the role of LC/MS/MS in steroidomics. This remains a challenge but offers
      shorter analysis times and advantages in the detection and discovery of steroids
      with a known structure. We describe recent advances in LC/MS steroidomics of
      hydrolyzed and intact steroid conjugates and suggest the technique is catching up
      with GC/MS in this area. However, in the end, both techniques will likely remain
      complementary and both should be available in advanced analytical laboratories.

PMID- 30094414
TI  - Isolated Periosteal Avulsion Fracture of the Teres Major in a Rugby Player.
AB  - We describe a case of an isolated periosteal avulsion fracture of the teres major
      tendon. A 29-year-old rugby player presented following a direct hit with his
      opponent followed by a fall on the ground. Clinical examination showed a limited
      and painful abduction of his left arm. MR-arthrography showed no capsulolabral
      lesions but revealed an extra-articular lesion at the origin of the teres major
      tendon. Follow-up radiography and CT showed progressive ossification of the
      lesion. To the best of our knowledge, this is the first case of a distal avulsion
      fracture of the teres major tendon reported in the imaging literature.

PMID- 30094415
TI  - Carotidynia Alias Transient Perivascular Inflammation of the Carotid Artery
      (TIPIC Syndrome).

PMID- 30094417
TI  - Ruthenium(ii)-catalyzed selective C-H difluoroalkylation of aniline derivatives
      with pyrimidyl auxiliaries.
AB  - A ruthenium-catalyzed alternative para- and meta-difluoroalkylation of anilines
      is herein reported. The reaction tolerates a broad range of aniline derivatives
      and provides a convenient approach for accessing the corresponding para/meta
      selective difluoroalkylated products. Mechanism studies demonstrated that the
      initial CAr-H and N-H cycloruthenation is the pivotal step in achieving remote C
      H difluoroacetylation.

PMID- 30094418
TI  - Elucidation of the two-step relaxation processes of a tetranuclear dysprosium
      molecular nanomagnet through magnetic dilution.
AB  - A new centrosymmetric tetranuclear aggregate [Dy4(L)2(OAc)8(CH3OH)2] (1) was
      assembled using a unique symmetrical Schiff base ligand 1,5-bis(salicylidene)
      carbohydrazide (H2L). Magnetic studies reveal ferromagnetic interactions between
      dysprosium ions and two obvious relaxation processes under zero dc field with
      effective energy barriers Ueff of 38 K and 223 K, the highest among the reported
      tetranuclear dysprosium molecular nanomagnets. To obtain further evidence on the
      origination of the slow magnetic relaxation, a diamagnetic yttrium analogue
      [Y4(L)2(OAc)8(CH3OH)2] (2) and a diluted sample
      [(Dy0.06Y0.94)4(L)2(OAc)8(CH3OH)2] (3) were synthesized. Further magnetic studies
      on the diluted sample combined with theoretical calculations indicate that the
      two-step magnetic relaxation processes in complex 1 originate from the single-ion
      magnetic behaviors of dysprosium ions with different coordination environments.

PMID- 30094416
TI  - T1- and T2-weighted Magnetic Resonance Dual Contrast by Single Core Truncated
      Cubic Iron Oxide Nanoparticles with Abrupt Cellular Internalization and Immune
      Evasion.
AB  - Conventional T1- or T2-weighted single mode contrast-enhanced magnetic resonance
      imaging (MRI) may produce false results. Thereby, there is a need to develop dual
      contrast agents, T1- and T2-weighted, for more accurate MRI imaging. The dual
      contrast agents should possess high magnetic resonance (MR) relaxivities,
      targeted tumor linking, and minimum recognition by the immune system. We have
      developed nitrodopamine-PEG grafted single core truncated cubic iron oxide
      nanoparticles (ND-PEG-tNCIOs) capable of producing marked dual contrasts in MRI
      with enhanced longitudinal and transverse relaxivities of 32 +/- 1.29 and 791 +/-
      38.39 mM-1 s-1, respectively. Furthermore, the ND-PEG-tNCIOs show excellent
      colloidal stability in physiological buffers and higher cellular internalization
      in cancerous cells than in phagocytic cells, indicating the immune evasive
      capability of the nanoparticles. These findings indicate that tNCIOs are strong
      candidates for dual contrast MRI imaging, which is vital for noninvasive real
      time detection of nascent cancer cells in vivo and for monitoring stem cells
      transplants.

PMID- 30094419
TI  - Palladium-catalyzed enantioselective carboannulation of 1,3-dienes with aryl
      iodides enables access to chiral indanes.
AB  - A palladium-catalyzed enantioselective carboannulation of 1,3-dienes and aryl
      iodides has been established by using a BINOL-based phosphoramidite ligand. This
      reaction proceeded via a tandem Heck-type insertion and asymmetric intramolecular
      Tsuji-Trost allylic alkylation, providing indane derivatives with high levels of
      enantioselectivity (up to >99% ee).

PMID- 30094421
TI  - A domino reaction of 2-isocyanophenyloxyacrylate and aryne to synthesize arenes
      with vicinal olefin and benzoxazole.
AB  - An unusual domino reaction of 2-isocyanophenyloxyacrylate and aryne has been
      disclosed. The present strategy experiences nucleophilic addition, Michael
      addition, carbon-oxygen cleavage, and cyclization, thus enabling the quick aryne
      vicinal difunctionalization by the installation of a benzoxazole and an olefin.

PMID- 30094422
TI  - o-Nitrobenzyl photoremovable groups with fluorescence uncaging reporting
      properties.
AB  - o-Nitrobenzyl (o-NB) derivatives are the most widely applied photoremovable
      groups for the study of dynamic biological processes. By introducing different
      substituents to the benzylic position we were able to generate a fluorescence
      signal upon irradiation. This signal originates from the formation of a
      nitrosoketone by-product able to achieve a keto-enol tautomerism leading to pi
      conjugated alpha-hydroxystilbene derivatives. These o-NB caging groups can be
      used to directly monitor the uncaging event by the release of a detectable
      fluorescent side-product.

PMID- 30094420
TI  - Directed evolution of excited state lifetime and brightness in FusionRed using a
      microfluidic sorter.
AB  - Green fluorescent proteins (GFP) and their blue, cyan and red counterparts offer
      unprecedented advantages as biological markers owing to their genetic
      encodability and straightforward expression in different organisms. Although
      significant advancements have been made towards engineering the key photo
      physical properties of red fluorescent proteins (RFPs), they continue to perform
      sub-optimally relative to GFP variants. Advanced engineering strategies are
      needed for further evolution of RFPs in the pursuit of improving their photo
      physics. In this report, a microfluidic sorter that discriminates members of a
      cell-based library based on their excited state lifetime and fluorescence
      intensity is used for the directed evolution of the photo-physical properties of
      FusionRed. In-flow measurements of the fluorescence lifetime are performed in a
      frequency-domain approach with sub-millisecond sampling times. Promising clones
      are sorted by optical force trapping with an infrared laser. Using this
      microfluidic sorter, mutants are generated with longer lifetimes than their
      precursor, FusionRed. This improvement in the excited state lifetime of the
      mutants leads to an increase in their fluorescence quantum yield up to 1.8-fold.
      In the course of evolution, we also identified one key mutation (L177M), which
      generated a mutant (FusionRed-M) that displayed ~2-fold higher brightness than
      its precursor upon expression in mammalian (HeLa) cells. Photo-physical and
      mutational analyses of clones isolated at the different stages of mutagenesis
      reveal the photo-physical evolution towards higher in vivo brightness.

PMID- 30094423
TI  - In situ synthesis and macroscale alignment of CsPbBr3 perovskite nanorods in a
      polymer matrix.
AB  - We report an in situ catalyst-free strategy to synthesize inorganic CsPbBr3
      perovskite nanorods in a polymer matrix (NRs-PM) with good dimensional control,
      outstanding optical properties and ultrahigh environmental stability.
      Polarization photoluminescence (PL) imaging with high spatial resolution was
      carried out for the first time on single nanorod (NR) and shows a relatively high
      local polarization ratio (~0.4) consistent with theoretical predictions based on
      a dielectric contrast model. We further demonstrate that macroscale alignment of
      the CsPbBr3 nanorods can be achieved through mechanically stretching the NRs-PM
      films at elevated temperature, without deteriorating the optical quality of the
      NRs. A polarization ratio of 0.23 is observed for these aligned NRs-PM films,
      suggesting their potential as polarized down-converters to increase the light
      efficiency in liquid crystal display (LCD) backlights.

PMID- 30094424
TI  - Pyridinic-N-dominated carbon frameworks with porous tungsten trioxide nano
      lamellae as a promising bi-functional catalyst for Li-oxygen batteries.
AB  - The rational design and synthetic route to fabricate hybrid materials with
      desirable electrocatalytic functionalities remain critical but still challenging
      for sustainable energy devices. Here, we constructed a tungsten trioxide nano
      lamellae chemically anchored with pyridinic-N-dominated doped CNT/graphene
      frameworks (W-NCG) via a general solution-based synthesis method. The detailed
      results indicated that this hybrid structure is composed of vacancy-defect
      abundant WO3 porous nanoflakes anchoring through or onto a 3D N-doped carbon
      matrix. After a facile post-annealing treatment, the W-NCG sample is utilized as
      a bi-functional catalyst for rechargeable lithium-oxygen batteries. The optimized
      sample with a large BET surface exhibits unprecedented ORR/OER activity in the
      cell, and satisfying specific capacity (~7850 mA h g-1) and cycling stability.
      This excellent electrochemical performance can be ascribed to the pseudo 3D
      structure with sufficient microspace and good electrical conductivity, which
      facilitate the high dispersion of active components and effectivly relieve the
      formation of large/irreversible Li2O2. As such, this porous W-NCG framework is a
      prospective high-performance cathode material for Li-O2 batteries.

PMID- 30094426
TI  - Synthesis of imidazopyridine-fused indoles via one-pot sequential Knoevenagel
      condensation and cross dehydrogenative coupling.
AB  - A simple and efficient strategy for the synthesis of imidazopyridine-fused
      indoles has been developed that involves one-pot sequential Knoevenagel
      condensation of readily available active methylene azoles with N-substituted-1H
      indole-3-carboxaldehydes or N-substituted-1H-indole-2-carboxaldehydes followed by
      palladium-catalyzed intramolecular cross dehydrogenative coupling reaction. A
      series of 36 derivatives was prepared by using this strategy. The products were
      obtained in moderate to excellent (32-94%) yields and showed broad substrate
      scope with tolerance of various functional groups and was amiable for gram scale
      preparation without problems.

PMID- 30094425
TI  - Pushing the limits of sensitivity and resolution for natural abundance 43Ca NMR
      using ultra-high magnetic field (35.2 T).
AB  - Natural abundance 43Ca solid state NMR experiments are reported for the first
      time at ultra-high magnetic field (35.2 T) on a series of Ca-(pyro)phosphate and
      Ca-oxalate materials, which are of biological relevance in relation to
      biomineralization processes and the formation of pathological calcifications. The
      significant gain in both sensitivity and resolution at 35.2 T leads to
      unprecedented insight into the structure of both crystalline and amorphous
      phases.

PMID- 30094427
TI  - The chameleonic reactivity of dilithio bis(alkylamido)cyclodiphosph(iii)azanes
      with chlorophosphines.
AB  - To synthesize a bis(diphosphinylamine) ligand for use in late-metal catalysis
      dilithio bis(tert-butylamido)cyclodiphosph(iii)azane was treated with two
      equivalents of (Ph)2PCl. The chlorodiphenylphosphine attacked the dilithium salt
      kinetically at phosphorus, followed by a rearrangement to an unsymmetrical P, N
      di-substituted product. Solid-state structures of both products were determined,
      and the activation energy for the rearrangement was measured. To gain further
      insight into the location of chlorophosphine attack (N versus P) on lithium
      diamides, dilithio bis(cyclohexylamido)cyclodiphosph(iii)azane or dilithio
      bis(tert-butylamido)cyclodisilazane was treated with two equivalents of PCl3. In
      each case only the symmetrically N,N'-substituted bis(PCl2) product was obtained
      and characterized by X-ray analysis. The structures of these latter compounds are
      unusual, because in both cases a bicyclic compound with a bis(amido) chelated,
      central P-Cl moiety was expected based on precedent. The two proximal and
      juxtaposed PCl2 groups may provide a starting point for potentially novel
      reactivity studies.

PMID- 30094428
TI  - Interband transitions in closed-shell vacancy containing graphene quantum dots
      complexed with heavy metals.
AB  - High-performance optical detection of toxic heavy metals by using graphene
      quantum dots (GQDs) requires a strong interaction between the metals and GQDs,
      which can be reached through a functionalization/immobilization procedure or
      doping effect. However, commonly used surface activation approaches induce
      toxicity into the analysis system and, therefore, are ineligible from the
      environmental point of view. Here, we show that artificial creation of vacancy
      type defects in GQDs can be a helpful means of intentional control of the active
      sites available for reaction with cadmium (Cd), mercury (Hg) and lead (Pb). Using
      restricted density functional theory (DFT) and time-dependent DFT (TD-DFT)
      methods, we predict the effect of vacancy complexes not previously studied to
      describe the binding ability of GQDs towards metal adsorbates. We also show that
      the interband absorption in closed-shell GQDs complexed with Cd, Hg and Pb is
      strongly dependent on the vacancy type and can be efficiently tuned to attain the
      desired coloration of the analysis system. The results suggest that the vacancy
      defects play an important role in governing the hybridization between locally
      excited (LE) and charge-transfer (CT) states of the GQDs. Based on the molecular
      orbital analysis and in-depth knowledge of excited states, the mechanisms
      underlying the interband absorption are discussed.

PMID- 30094429
TI  - Using polyoxometalates to enhance the capacity of lithium-oxygen batteries.
AB  - The Keggin-type polyoxometalate alpha-SiW12O404- increases the discharge capacity
      and potential of lithium-oxygen batteries, by facilitating the reduction of O2 to
      Li2O2, as confirmed by in situ electrochemical pressure measurements and XRD.
      Compared to organic redox mediators, polyoxometalates have higher chemical and
      structural stability, which could lead to longer cycling lithium-oxygen
      batteries.

PMID- 30094430
TI  - Free-standing nanostructured vanadium pentoxide films for metal-ion batteries.
AB  - Owing to their unique layer structure, high aspect ratio and intercalation
      capability, vanadium pentoxide (V2O5) nanofibers are close-to-ideal building
      blocks for high performance electrodes for metal-ion batteries. However, thus far
      investigated electrodes composed of V2O5 nanofibers mostly contain binders and
      conductive agents, which reduce the electrodes' gravimetric capacity. Here we
      demonstrate self-supporting V2O5 nanofiber-based films that combine high
      mechanical flexibility and stability with good electrical conductivity. This has
      been achieved by suitable adjustment of the nanofiber length, in combination with
      a suitable humidity controlled post-treatment, to ensure an effective nanofiber
      interconnection and aging of the films. The optimization of these two parameters
      allows for an impressive 81%, 184%, and 281% enhancement in Young's modulus,
      tensile strength and toughness respectively, along with an increase of electrical
      conductivity by up to 165%. Such films can reach storage capacities of up to 150
      mA h g-1 without the support of conductive agents and binders. Our findings
      provide fundamental design guidelines for advanced binder-free electrode
      materials, which unite high specific storage capacity, excellent mechanical
      stability and good intrinsic electrical conductivity - the key to technologically
      advanced battery performance and lifetime.

PMID- 30094431
TI  - How does the electric current propagate through fully-hydrogenated borophene?
AB  - We study the electronic transport properties of two-dimensional (2D) fully
      hydrogenated borophene (namely, borophane), using density functional theory and
      non-equilibrium Green's function approaches. Borophane shows a perfect electrical
      transport anisotropy and is promising for applications. Along the peak- or
      equivalently the valley-parallel direction, 2D borophane exhibits a metallic
      characteristic and its current-voltage (I-V) curve shows a linear behavior,
      corresponding to the ON state in borophane-based nano-switches. In this case,
      electrons mainly propagate via the B-B bonds along the linear boron chains. In
      contrast, electron transmission is almost forbidden along the perpendicular
      buckled direction (i.e., the OFF state), due to its semi-conductor property. Our
      work demonstrates that 2D borophane could combine metal and semiconductor
      features and may be a promising candidate for nano-switching materials with a
      stable structure and high ON/OFF ratio.

PMID- 30094432
TI  - Novel quinoxalinone-based push-pull chromophores with highly sensitive emission
      and absorption properties towards small structural modifications.
AB  - The photophysical properties of a series of novel push-pull quinoxalinone-based
      chromophores that strongly absorb and emit light in the broad visible spectrum
      were comprehensively studied both experimentally and through quantum chemical
      methods. The drastic influence of the position of the electron-donor
      dimethylaminostyryl (DMAS) in the quinoxalinone core on its absorption and
      emission intensities as well as on the solvatochromic behavior of the concerned
      isomers has been established. No dependence of the photophysical properties of
      the chromophores on the conformation of the DMAS group was found. Quantum
      chemical computations provided a reliable theoretical rationalization of the
      observed spectral features, in particular, the important one related to Stokes
      shift. The local or intramolecular charge-transfer (ICT) character of the key
      electronic transitions has been assessed using a quantitative natural transition
      orbitals analysis and based on the novel topological descriptors of the
      electronic density rearrangement. This study shows that the ICT effects are not
      the primary factors contributing to the drastic difference in the emission
      efficiency of push-pull chromophores that are structurally very similar.

PMID- 30094433
TI  - Repulsion-dispersion parameters for the modelling of organic molecular crystals
      containing N, O, S and Cl.
AB  - In lattice energy models that combine ab initio and empirical components, it is
      important to ensure consistency between these components so that meaningful
      quantitative results are obtained. A method for deriving parameters of atom-atom
      repulsion dispersion potentials for crystals, tailored to different ab initio
      models, is presented. It is based on minimization of the sum of squared
      deviations between experimental and calculated structures and energies. The
      solution algorithm is designed to avoid convergence to local minima in the
      parameter space by combining a deterministic low-discrepancy sequence for the
      generation of multiple initial parameter guesses with an efficient local
      minimization algorithm. The proposed approach is applied to derive transferable
      exp-6 potential parameters suitable for use in conjunction with a distributed
      multipole electrostatics model derived from isolated molecule charge densities
      calculated at the M06/6-31G(d,p) level of theory. Data for hydrocarbons,
      azahydrocarbons, oxohydrocarbons, organosulphur compounds and chlorohydrocarbons
      are used for the estimation. A good fit is achieved for the new set of parameters
      with a mean absolute error in sublimation enthalpies of 4.1 kJ mol-1 and an
      average rmsd15 of 0.31 A. The parameters are found to perform well on a separate
      cross-validation set of 39 compounds.

PMID- 30094434
TI  - Distributed fibre optofluidic laser for chip-scale arrayed biochemical sensing.
AB  - Optofluidic lasers (OFLs) are an emerging technological platform for biochemical
      sensing, and their good performance especially high sensitivity has been
      demonstrated. However, high-throughput detection with an OFL remains a major
      challenge due to the lack of reproducible optical microcavities. Here, we
      introduce the concept of a distributed fibre optofluidic laser (DFOFL) and
      demonstrate its potential for high-throughput sensing applications. Due to the
      precise fibre geometry control via fibre drawing, a series of identical optical
      microcavities uniformly distributed along a hollow optical fibre (HOF) can be
      achieved to obtain a one-dimensional (1D) DFOFL. An enzymatic reaction catalysed
      by horseradish peroxidase (HRP) can be monitored over time, and the HRP
      concentration is detected by DFOFL-based arrayed colorimetric detection.
      Experimentally, five-channel detection in parallel with imaging has been
      demonstrated. Theoretically, spatial multiplexing of hundreds of channels is
      achievable with DFOFL-based detection. The DFOFL wavelength is tuned over
      hundreds of nanometers by optimizing the dye concentration or reconfiguring the
      liquid gain materials. Extending this concept to a two-dimensional (2D) chip
      through wavelength multiplexing can further enhance its multi-functionality,
      including multi-sample detection and spectral analysis. This work opens the door
      to high-throughput biochemical sensing.

PMID- 30094435
TI  - Electronic effects of the Bernal stacking of graphite on self-assembled aromatic
      adsorbates.
AB  - We compare by Scanning Tunneling Microscopy (STM) self-organized honeycomb
      monolayers of aromatic molecules formed either on graphite or on graphene. A
      differential contrast between the adsorption sites observed exclusively on
      graphite evidences the electronic effects of the symmetry breaking by the
      staggered atomic layers forming this substrate.

PMID- 30094437
TI  - Effects of oat protein supplementation on skeletal muscle damage, inflammation
      and performance recovery following downhill running in untrained collegiate men.
AB  - The positive influence of animal-based protein supplementation during muscle
      damaging exercise has been widely studied. However, the effects of plant-based
      proteins remain unclear and require further clarification. This study
      investigated the protective role of oat protein against exercise induced muscle
      damage (EIMD), subsequent inflammation, and loss of performance induced by
      downhill running. Subjects consumed either oat protein (25 g protein) or a
      placebo for 14 days prior to a downhill running test and then for 4 days
      thereafter. Treatments with oat protein for 19 days markedly alleviated eccentric
      exercise induced skeletal muscle soreness, and reduced the elevation of plasma IL
      6 concentrations and serum creatine kinase, myoglobin and C reactive protein
      contents. In addition, oat protein supplementation significantly inhibited limb
      edema following damaging exercise, and the adverse effects on muscle strength,
      knee-joint range of motion, and vertical jump performance were lessened.
      Furthermore, the administration of oat protein facilitated recovery from
      exhaustive downhill running in this study. These findings demonstrated that oat
      protein supplementation has the potential to alleviate the negative effects of
      eccentric exercise in untrained young males.

PMID- 30094438
TI  - Cu-Catalyzed/mediated synthesis of N-fluoroalkylanilines from arylboronic acids:
      fluorine effect on the reactivity of fluoroalkylamines.
AB  - An oxidative coupling reaction of fluoroalkylamines with arylboronic acids has
      been achieved for the first time. Fluorine has profound influence on the
      reactivity and fluoroalkylated amines have the following reactivity trend:
      difluoroethylamine > trifluoroethylamine > pentafluoropropylamine ~
      heptafluorobutylamine.

PMID- 30094436
TI  - A cytotoxic tantalum(v) half-sandwich complex: a new challenge for metal-based
      anticancer agents.
AB  - Despite the biological relevance of complexes of various transition metals,
      tantalum complexes have long been neglected by bioinorganic chemists. Herein, we
      demonstrate potential chemotherapeutic applicability of the [Ta(eta5
      Cp*)Cl2(salaph)] (1) complex, containing deprotonated Schiff base 2-{(E)-[(2
      hydroxyphenyl)imino]methyl}phenol (H2salaph), which shows strong cytotoxicity in
      cancer cells, related to the induction of apoptosis and apoptosis-related
      processes, but shows low cytotoxicity in healthy cells.

PMID- 30094439
TI  - Theory as a driving force to understand reactions on nanoparticles: general
      discussion.

PMID- 30094440
TI  - Cofacial porphyrin dimers assembled from N-heterocyclic carbene-metal bonds.
AB  - A porphyrin bearing four imidazolium rings on the meso positions was used as an N
      heterocyclic carbene (NHC) precursor for the synthesis of porphyrin dimers with
      face-to-face orientations. The porphyrins are connected through the formation of
      eight M-CNHC bonds, with M = AgI or AuI.

PMID- 30094441
TI  - Inflating face-capped Pd6L8 coordination cages.
AB  - Tritopic metalloligands were used to form two Pd6L8-type coordination cages. With
      molecular weights of more than 15 kDa and PdPd distances of up to 4.2 nm, these
      complexes are among the largest palladium cages described to date.

PMID- 30094442
TI  - Designed formation of Co3O4/ZnCo2O4/CuO hollow polyhedral nanocages derived from
      zeolitic imidazolate framework-67 for high-performance supercapacitors.
AB  - Zeolitic imidazolate frameworks have stimulated great attention due to their
      potential applications in energy storage, catalysis, gas sensing, drug delivery
      etc. In this paper, the three-dimensional porous nanomaterial Co3O4/ZnCo2O4/CuO
      with hollow polyhedral nanocage structures and highly enhanced electrochemical
      performances was synthesized successfully by a zeolitic imidazolate framework-67
      route. The composites hold the shape of the ZIF-67 templates well and the shell
      has multiple compositions. In the process, we first synthesized the nanostructure
      hydroxide precursors and then transformed them into the corresponding metal oxide
      composites by thermal annealing in air. In addition, the mass ratio of Zn to Cu
      in this material is discussed and optimized. We found that when the mass ratio is
      3, the composite material has better electrochemical properties. When applied as
      an electrode material, Co3O4/ZnCo2O4/CuO-1 shows enhanced pseudocapacitive
      properties and good cycling stability compared with Co3O4/ZnCo2O4, Co3O4/CuO and
      Co3O4/ZnCo2O4/CuO-2, and Co3O4/ZnCo2O4/CuO-3. The assembled Co3O4/ZnCo2O4/CuO
      1//AC hybrid device can be reversibly cycled in a large potential range of 0-1.6
      V and can deliver a high energy density of 35.82 W h kg-1 as well as the maximum
      power density of 4799.25 W kg-1.

PMID- 30094444
TI  - Hydrogen bond induced enhancement of Fermi resonances in N-HN hydrogen bonded
      complexes of anilines.
AB  - The hydrogen-bonded complexes of aniline, 4-fluoroaniline and 4-ethynylaniline
      with ammonia, methylamine, dimethylamine, trimethylamine and triethylamine, were
      investigated using IR-UV double resonance spectroscopy. The formation of N-HN
      hydrogen bonded complexes with anilines as donors and alkylamines as acceptors
      was inferred from the appearance of the spectra. Two bands appearing in the 3100
      3400 cm-1 region were found to be originating from the Fermi resonance coupling
      between the hydrogen-bonded NH2 stretching and NH2 bend-overtone vibrations. A
      two-state de-perturbation analysis yields the zero-order (unperturbed)
      vibrational states and the coupling constant. An inverse correlation between the
      zero-order hydrogen-bonded NH2 stretching and NH2 bend-overtone was observed due
      to a switch in the relative contributions of hydrogen-bonded NH2 stretching and
      NH2 bend-overtone vibrations to the Fermi resonance bands. These results lead to
      the reassignment of the hydrogen-bonded N-H stretching frequencies of aniline
      complexes reported earlier. Furthermore, the stretch-bend Fermi-resonance
      coupling constant for the NH2 group is around 50 cm-1, which is independent of
      the nature of the parent donor molecule and the acceptor, and is intrinsic to the
      NH2 group.

PMID- 30094443
TI  - Development of a novel inducer of protein-protein interactions based on
      aplyronine A.
AB  - An aplyronine A-swinholide A hybrid, consisting of the macrolactone part of
      aplyronine A and the side chain part of swinholide A, was designed, synthesized,
      and evaluated for biological activities. The hybrid retained strong cytotoxicity
      and actin-depolymerizing activity. In addition, the hybrid induced protein
      protein interactions (PPI) between actin and tubulin in the manner of aplyronine
      A.

PMID- 30094445
TI  - Atomistic reverse nonequilibrium molecular dynamics simulation of the viscosity
      of ionic liquid 1-n-butyl 3-methylimidazolium bis(trifluoromethylsulfonyl)imide
      [bmim][Tf2N].
AB  - The shear viscosity of room-temperature ionic liquid (IL) 1-n-butyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide [bmim][Tf2N] is calculated
      over a temperature range 298-353 K, using the reverse nonequilibrium molecular
      dynamics simulation technique. The results of this work show that while the use
      of equilibrium molecular dynamics simulation techniques might be inefficient for
      viscosity calculations of ILs, the reverse nonequilibrium molecular dynamics
      technique is an efficient tool for this purpose. Our findings indicate that the
      shear rate for crossover from the Newtonian plateau to the shear thinning regime,
      corresponds to the relaxation time for the slowest microscopic scale motions,
      i.e., exchange of counterions in an ion's solvation shell (ion-pair relaxation
      time). The closeness of the time scales and activation energies for zero-shear
      rate viscosities to the relaxation times and the corresponding activation
      energies for ion-pair formation/rupture, connects macroscopic dynamic properties
      with local atomic-level motions of the IL. The calculated viscosity coefficients
      and relaxation times for reorientations of the cation and anion as well as their
      corresponding activation energies are in very good agreement with experimental
      data.

PMID- 30094446
TI  - New opportunities for efficient N2 fixation by nanosheet photocatalysts.
AB  - Catalytic ammonia synthesis from dinitrogen (N2) under mild conditions has been
      considered to be the "holy grail" of N2 fixation, which is one of the most
      important chemical processes in the agriculture, biological and industrial
      fields. Given that current artificial N2 fixation is still dominated by the
      energy-intensive Haber-Bosch process, solar N2 fixation represents an encouraging
      and fascinating route for carbon-free and energy-saving N2 fixation. However, its
      practical application is seriously hampered by surface sluggish reaction
      kinetics. In this minireview, we share our perspectives on the use of two
      dimensional (2D) nanosheets for the manipulation of photocatalytic N2 fixation.
      Nanosheet photocatalysts serve as the perfect platform for the engineering of
      surface active sites, including defects and iron, all of which can not only
      bolster photon-exciton interaction toward robust charge carriers generation upon
      light absorption, but also mimic the function schemes of MoFe-cofactor in
      nitrogenase toward sufficient N2 binding and activation. These merits endowed by
      nanosheets photocatalysts provide instructive information on exploring the rich
      nitrogen photochemistry on solid surfaces and offer new opportunities for the
      design of novel photocatalysts towards efficient N2 fixation.

PMID- 30094447
TI  - Effects of hydrogen bonding on the gas-phase reactivity of
      didehydroisoquinolinium cation isomers.
AB  - Two previously unreported isomeric biradicals with a 1,4-radical topology, the
      1,5-didehydroisoquinolinium cation and the 4,8-didehydroisoquinolinium cation,
      and an additional, previously reported isomer, the 4,5-didehydroisoquinolinium
      cation, were studied to examine the importance of the exact location of the
      radical sites on their reactivities in the gas phase. The experimental results
      suggest that hydrogen bonding in the transition state enhances the reactivity of
      the 1,5-didehydroisoquinolinium cation towards tetrahydrofuran but not towards
      allyl iodide, dimethyl disulfide or tert-butyl isocyanide. The observation of no
      such enhancement of reactivity towards tetrahydrofuran for the 4,8
      didehydroisoquinolinium and 4,5-didehydroisoquinolinium cations supports this
      hypothesis as these two biradicals are not able to engage in hydrogen bonding in
      their transition states for hydrogen atom abstraction from tetrahydrofuran.
      Quantum chemical transition state calculations indicate that abstraction of a
      hydrogen atom from tetrahydrofuran by the 1,5-didehydroisoquinolinium cation
      occurs at the C-1 radical site and that the transition state is stabilized by
      hydrogen bonding.

PMID- 30094449
TI  - Crystallization kinetics of water on graphite.
AB  - Graphite is hydrophobic in nature, but the crystallization kinetics and dewetting
      transition of thin water films deposited onto graphite are distinct from those on
      typical hydrophobic substrates. To clarify the origin of these behaviors, we
      investigated the crystallization kinetics of thin water films on graphite in
      terms of the initial film thickness, deposition temperature, and template effects
      of adspecies based on reflection high-energy electron diffraction (RHEED) images;
      the film morphology change was analyzed using time-of-flight secondary ion mass
      spectrometry (TOF-SIMS). The water monolayer nucleates after surface diffusivity
      occurs at ca. 120 K; the nucleation temperature and time increase with increasing
      initial film thickness. Crystallites of cubic and hexagonal ices are formed,
      having preferred orientation [cubic (111) or hexagonal (001)] along the surface
      normal direction; their relative quantity depends on the initial film thickness
      and the way of crystallization. Randomly oriented crystallites finally grow via
      spontaneous nucleation when the film thickness exceeds 7-10 monolayers. The
      template ordering effects of graphite are quenched when a monolayer of ordered n
      octane preexists at the substrate interface. The crystalline ice tends to wet the
      graphite substrate immediately after nucleation, and the film morphology changes
      gradually at 130 K because of premelting. The crystallites are ripened via
      molecular transport through the quasiliquid layer formed at the free surface,
      grain boundaries, and substrate.

PMID- 30094450
TI  - Preparation of gas phase naked silver cluster cations outside a mass spectrometer
      from ligand protected clusters in solution.
AB  - Gas phase clusters of noble metals prepared by laser desorption from the bulk
      have been investigated extensively in a vacuum using mass spectrometry. However,
      such clusters have not been known to exist under ambient conditions to date. In
      our previous work, we have shown that in-source fragmentation of ligands can be
      achieved starting from hydride and phosphine co-protected silver clusters leading
      to naked silver clusters inside a mass spectrometer. In a recent series of
      experiments, we have found that systematic desorption of ligands of the monolayer
      protected atomically precise silver cluster can also occur in the atmospheric gas
      phase. Here, we present the results, wherein the [Ag18H16(TPP)10]2+ (TPP =
      triphenylphosphine) cluster results in the formation of the naked cluster, Ag17+
      along with Ag18H+ without mass selection, outside the mass spectrometer, in air.
      These cationic naked metal clusters are prepared by passing electrosprayed ligand
      protected clusters through a heated tube, in the gas phase. Reactions with oxygen
      suggest Ag17+ to be more reactive than Ag18H+, in agreement with their electronic
      structures. The more common thiolate protected clusters produce fragments of
      metal thiolates under identical processing conditions and no naked clusters were
      observed.

PMID- 30094448
TI  - Effect of polymer charge on functional reconstitution of membrane proteins in
      polymer nanodiscs.
AB  - Although there is a growing interest in using polymer lipid-nanodiscs, the
      polymer charge poses limitations for studies on membrane proteins. Here, we
      demonstrate the functional reconstitution of a large soluble-domain containing
      positively-charged ~57 kDa cytochrome-P450 and negatively-charged ~16 kDa
      cytochrome-b5 in lipid-nanodiscs, and the role of the polymer charge for high
      resolution studies on membrane proteins.

PMID- 30094451
TI  - Coordination of a stibine oxide to a Lewis acidic stiborane at the upper rim of
      the biphenylene backbone.
AB  - Our interest in bifunctional antimony Lewis acids has led us to synthesize 1,8
      bis(diphenylstibino)biphenylene (2) by reaction of 1,8
      bis(trimethylstannyl)biphenylene (1) with Ph2SbCl. Oxidation of this distibine
      with o-chloranil, followed by work-up in air afforded a biphenylene derivative
      (3) featuring a triarylstibine oxide connected via an Sb[double bond, length as m
      dash]O -> Sb bridge to the neighbouring antimony(v) center.

PMID- 30094452
TI  - A spectroscopic and ab initio study of the hydrogen peroxide-formic acid complex:
      hindering the internal motion of H2O2.
AB  - The microwave spectrum of the hydrogen-bonded hydrogen peroxide-formic acid
      complex was measured in the range from 4 to 17 GHz. Assignment of transitions and
      analyses of the spectrum were supported by ab initio wavefunction and density
      functional calculations. The detected conformer features a seven-membered
      hydrogen-bonded ring, in which the H-atom of one hydroxyl group of H2O2 and the O
      atom of the other OH group are a hydrogen bond donor and acceptor, respectively,
      to the carboxyl group of formic acid. The rotational transitions show a
      tunnelling splitting, which is attributed to a wagging-like motion of the free H
      atom of H2O2 from above to below the heavy atom plane of formic acid. Transitions
      between tunneling states are driven by the change in dipole moment accompanying
      this motion and were measured and analyzed. Ab initio analyses of the tunneling
      path reveal an asymmetric potential, which reflects the (transiently) chiral
      nature of the complex.

PMID- 30094454
TI  - Facile synthesis of silver nanowire-zeolitic imidazolate framework 67 composites
      as high-performance bifunctional oxygen catalysts.
AB  - The development of inexpensive, highly active, bifunctional electrocatalysts for
      oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) is required
      for many energy conversion systems, including water splitting, fuel cells, and
      metal-air batteries. This study reports silver nanowires-zeolitic imidazolate
      framework (Ag NWs-ZIF67) composites as bifunctional electrocatalysts for OER and
      ORR. The synergistic effects of Co2+, organic ligands, and Ag NWs enhance the
      bifunctional electrocatalytic properties. Ag NWs improved the electrical
      conductivity of the Ag NWs-ZIF67 composite toward OER, and porous ZIF-67 on the
      exterior of this product enabled O2 to fully react with Ag NWs for the ORR
      because O2 molecules were easily deflected from a planar electrode surface. This
      study provides valuable insights into the rational design of bifunctional oxygen
      catalysts having advantages of high performance and low cost.

PMID- 30094453
TI  - Transient DNA damage following exposure to gold nanoparticles.
AB  - Due to their interesting physicochemical properties, gold nanoparticles (Au-NPs)
      are the focus of increasing attention in the field of biomedicine and are under
      consideration for use in drug delivery and bioimaging, or as radiosensitizers and
      nano-based vaccines. Thorough evaluation of the genotoxic potential of Au-NPs is
      required, since damage to the genome can remain undetected in standard hazard
      assessments. Available genotoxicity data is either limited or contradictory.
      Here, we examined the influence of three surface modified 3-4 nm Au-NPs on human
      A549 cells, according to the reactive oxygen species (ROS) paradigm. After 24 h
      of Au-NP treatment, nanoparticles were taken up by cells as agglomerates;
      however, no influence on cell viability or inflammation was detected. No increase
      in ROS production was observed by H2-DCF assay; however, intracellular
      glutathione levels reduced over time, indicating oxidative stress. All three
      types of Au-NPs induced DNA damage, as detected by alkaline comet assay. The
      strongest genotoxic effect was observed for positively charged Au-NP I. Further
      analysis of Au-NP I by neutral comet assay, fluorimetric detection of alkaline
      DNA unwinding assay, and gammaH2AX staining, revealed that the induced DNA
      lesions were predominantly alkali-labile sites. As highly controlled repair
      mechanisms have evolved to remove a wide range of DNA lesions with great
      efficiency, it is important to focus on both acute cyto- and genotoxicity,
      alongside post-treatment effects and DNA repair. We demonstrate that Au-NP
      induced DNA damage is largely repaired over time, indicating that the observed
      damage is of transient nature.

PMID- 30094455
TI  - Low-field giant magneto-ionic response in polymer-based nanocomposites.
AB  - The future of magnetoelectric (ME) materials is closely linked to the
      optimization of the ME response on nanocomposites or to the introduction of new
      effects to achieve higher ME performance from low magnetic fields. Here, we
      report a P(VDF-TrFE)/[C4mim][FeCl4] nanocomposite with a magneto-ionic response
      that produces giant magnetoelectric coefficients up to ~10 V cm-1 Oe-1. This
      response comprises a magnetically triggered ionic/charge movement within the
      porous structure of the polymer, being this a novel phenomenon never
      experimentally observed or explored in magnetoelectric composites. This work
      successfully demonstrates the concept of exploring magnetic ionic liquids, such
      as [C4mim][FeCl4], in polymer-based magnetoelectric nanocomposites, suitable for
      low-field magnetic sensing devices. Such nanocomposites have remarkable potential
      for applications, not only because they exhibit a high ME response with scalable
      production and with good reproducibility but also because this coupling between
      magnetic order and electric order via ionic effects can lead to additional novel
      effects.

PMID- 30094456
TI  - Mapping a gene on wheat chromosome 4BL involved in a complementary interaction
      with adult plant leaf rust resistance gene LrSV2.
AB  - KEY MESSAGE: A complementary gene to LrSV2 for specific adult plant leaf rust
      resistance in wheat was mapped on chromosome 4BL, tightly linked to Lr12 / 31.
      LrSV2 is a race-specific adult plant leaf rust (Puccinia triticina) resistance
      gene on subdistal chromosome 3BS detected in the cross of the traditional
      Argentinean wheat (Triticum aestivum) variety Sinvalocho MA and the experimental
      line Gama6. The analysis of the cross of R46 [recombinant inbred line (RIL)
      derived from Sinvalocho MA carrying LrSV2 gene and the complementary gene Lrc-SV2
      identified in the current paper] and the commercial variety Relmo Siriri (not
      carrying neither of these two genes) allowed the detection of the unlinked
      complementary gene Lrc-SV2 because the presence of one dominant allele of both is
      necessary to express the LrSV2-specific adult plant resistance. Lrc-SV2 was
      mapped within a 1-cM interval on chromosome 4BL using 100 RILs from the cross
      Sinvalocho MA * Purple Straw. This genetic system resembles the Lr27+31 seedling
      resistance reported in the Australian varieties Gatcher and Timgalen where
      interacting genes map at similar chromosomal positions. However, in high
      resolution maps, Lr27 and LrSV2 were already mapped to adjacent intervals on 3BS
      and Lrc-SV2 map position on 4BL is distal to the reported Lr12/31-flanking
      microsatellites.

PMID- 30094459
TI  - Healing the web of life: on the meaning of environmental and health equity.

PMID- 30094457
TI  - Novel gene Sen2 conferring broad-spectrum resistance to Synchytrium endobioticum
      mapped to potato chromosome XI.
AB  - Key message Sen2 gene for potato wart resistance, located on chromosome XI in a
      locus distinct from Sen1 , provides resistance against eight wart pathotypes,
      including the virulent ones important in Europe. Synchytrium endobioticum causes
      potato wart disease imposing severe losses in potato production, and as a
      quarantine pathogen in many countries, it results in lost trade markets and land
      for potato cultivation. The resistance to S. endobioticum pathotype 1(D1) is
      widespread in potato cultivars but new virulent pathotypes appear and the problem
      re-emerges. To characterize and map a new gene for resistance to potato wart, we
      used diploid F1 potato population from a cross of potato clone resistant to S.
      endobioticum pathotype 1(D1) and virulent pathotypes: 2(G1), 6(O1), 8(F1),
      18(T1), 2(Ch1), 3(M1) and 39(P1) with a potato clone resistant to pathotype 1(D1)
      only. The 176 progeny clones were tested for resistance to eight wart pathotypes
      with a modified Glynne-Lemmerzahl method. Bimodal distributions and co
      segregation of resistance in the population show that a single resistance gene,
      Sen2, underlies the resistance to eight pathotypes. Resistance to pathotype 1(D1)
      was additionally conferred by the locus Sen1 inherited from both parents. Sen2
      was mapped to chromosome XI using DArTseq markers. The genetic and physical
      distances between Sen1 and Sen2 loci were indirectly estimated at 63 cM and 32
      Mbp, respectively. We developed PCR markers co-segregating with the Sen2 locus
      that can be applied in marker-assisted selection of potatoes resistant to eight
      important pathotypes of S. endobioticum. Wide spectrum of the Sen2 resistance may
      be an indication of durability which can be enhanced by the pyramiding of the
      Sen2 and Sen1 loci as in 61 clones selected within this study.

PMID- 30094461
TI  - Diagnostic performance of choline PET for detection of hyperfunctioning
      parathyroid glands in hyperparathyroidism: a systematic review and meta-analysis.
AB  - PURPOSE: Hyperparathyroidism (HPT) is a common endocrine disorder caused by
      hyperfunctioning parathyroid glands (HP). The correct detection and localization
      of HP is challenging but crucial, as it may guide surgical treatment,
      particularly in patients with primary HPT. There is a growing body of data
      regarding the role of radiolabelled choline positron emission tomography (PET) in
      this setting. Therefore, we performed a systematic review and meta-analysis of
      the diagnostic performance of this method in detecting HP in patients with HPT.
      METHODS: This systematic review and meta-analysis was carried out according to
      PRISMA guidelines. A comprehensive computer literature search of PubMed/MEDLINE,
      EMBASE and Cochrane Library databases for studies published through May 2018 was
      performed using the following search algorithm: (a) "choline" or "fluorocholine"
      or "F-choline" or "C-choline" or "FCH" or "CH" or "FECH" or "FMCH" and (b) "PET"
      or "positron emission tomography" and (c) "parathyroid" or "hyperparathyroidism".
      The diagnostic performance of radiolabelled choline PET was expressed as
      sensitivity and positive predictive value (PPV) on a per-patient and per-lesion
      basis and as detection rate (DR) on a per-patient basis, with pooled proportion
      and 95% confidence interval (95% CI) obtained using a random-effects model.
      RESULTS: Eighteen studies were included in the systematic review. Fourteen
      articles (517 patients) were selected for the meta-analysis. The meta-analysis
      provided the following results on a per-patient analysis analysis: sensitivity
      95% (95% CI: 92-97%), PPV 97% (95% CI: 95-98%) and DR 91% (95% CI: 87-94%). On a
      per-lesion analysis, pooled sensitivity and PPV were 92% (95% CI: 88-96) and 92%
      (95% CI: 89-95%), respectively. No significant heterogeneity was found among the
      selected studies. CONCLUSIONS: Radiolabelled choline PET demonstrated excellent
      diagnostic performance in detecting HP in patients with HPT. Large multicentre
      studies and cost-effectiveness analyses are needed to better define the role of
      this imaging method in this setting.

PMID- 30094460
TI  - Radiomics analysis of pre-treatment [18F]FDG PET/CT for patients with metastatic
      colorectal cancer undergoing palliative systemic treatment.
AB  - BACKGROUND: The aim of this study was to assess radiomics features on pre
      treatment [18F]FDG positron emission tomography (PET) as potential biomarkers for
      response and survival in patients with metastatic colorectal cancer (mCRC).
      METHODS: Patients with mCRC underwent [18F]FDG PET/computed tomography (CT) prior
      to first- or third-line palliative systemic treatment. Tumour lesions were
      semiautomatically delineated and standard uptake value (SUV), metabolically
      active tumour volume (MATV), total lesion glycolysis (TLG), entropy, area under
      the curve of the cumulative SUV-volume histogram (AUC-CSH), compactness and
      sphericity were obtained. RESULTS: Lesions of 47 patients receiving third-line
      systemic treatment had higher SUVmax, SUVpeak, SUVmean, MATV and TLG, and lower
      AUC-CSH, compactness and sphericity compared to 52 patients receiving first-line
      systemic treatment. Therefore, first- and third-line groups were evaluated
      separately. In the first-line group, anatomical changes on CT correlated
      negatively with TLG (rho = 0.31) and MATV (rho = 0.36), and positively with
      compactness (rho = -0.27) and sphericity (rho = -0.27). Patients without benefit
      had higher mean entropy (p = 0.021). Progression-free survival (PFS) and overall
      survival (OS) were worse with a decreased mean AUC [hazard ratio (HR) 0.86, HR
      0.77] and increase in mean MATV (HR 1.15, HR 1.22), sum MATV (HR 1.14, HR 1.19),
      mean TLG (HR 1.16, HR 1.22) and sum TLG (HT1.12, HR1.18). In the third-line
      group, AUC-CSH correlated negatively with anatomical change (rho = 0.21). PFS and
      OS were worse with an increased mean MATV (HR 1.27, HR 1.68), sum MATV (HR 1.35,
      HR 2.04), mean TLG (HR 1.29, HR 1.52) and sum TLG (HT 1.27, HR 1.80). SUVmax and
      SUVpeak negatively correlated with OS (HR 1.19, HR 1.21). Cluster analysis of the
      10 radiomics features demonstrated no complementary value in identifying
      aggressively growing lesions or patients with impaired survival. CONCLUSION: We
      demonstrated an association between improved clinical outcome and pre-treatment
      low tumour volume and heterogeneity as well as high sphericity on [18F]FDG PET.
      Future PET imaging research should include radiomics features that incorporate
      tumour volume and heterogeneity when correlating PET data with clinical outcome.

PMID- 30094462
TI  - Amyloid imaging for differential diagnosis of dementia: incremental value
      compared to clinical diagnosis and [18F]FDG PET.
AB  - PURPOSE: Cerebral beta-amyloid and regional glucose metabolism assessed by
      positron emission tomography (PET) are used as diagnostic biomarkers for
      Alzheimer's disease (AD). The present study validates the incremental diagnostic
      value of amyloid PET in addition to clinical diagnosis and [18F]FDG PET in a real
      life memory clinic population. METHODS: Of 138 consecutive patients with
      cognitive impairment who received combined [18F]FDG and [11C]PIB PET, 84 were
      diagnosed with major neurocognitive disorder (DSM-5) and included. Baseline
      clinical and [18F]FDG PET diagnoses were independently established with and
      without access to amyloid PET results and were dichotomized into AD or non-AD
      disorders. The incremental value of amyloid PET was evaluated in terms of: (1)
      the change in clinical and [18F]FDG PET diagnoses, (2) the change in agreement
      between clinical and [18F]FDG PET diagnoses, and (3) diagnostic accuracy using an
      interdisciplinary consensus diagnosis after an extended follow-up (2.4 +/- 1.3
      years after PET) as the reference. RESULTS: After disclosure of the amyloid PET
      results, clinical and [18F]FDG PET diagnoses changed in 23% and 18% of patients,
      respectively, and agreement between both ratings increased from 62% to 86% (p <
      0.001). The accuracy of clinical and [18F]FDG PET diagnoses improved from 71% to
      89% (p < 0.01) and from 76% to 94% (p < 0.001), respectively. The additional
      value of amyloid PET was rather uniform in relation to age at onset and
      consistency with appropriate use criteria. CONCLUSION: Amyloid PET provides
      significant incremental diagnostic value beyond clinical and [18F]FDG PET
      diagnoses of AD. Given the high diagnostic accuracy of combined clinical and
      amyloid PET assessment, further studies are needed to clarify the role of an
      additional [18F]FDG PET scan in these patients.

PMID- 30094458
TI  - DPCPX, a selective adenosine A1 receptor antagonist, enhances the antidepressant
      like effects of imipramine, escitalopram, and reboxetine in mice behavioral
      tests.
AB  - The main goal of the present study was to evaluate the influence of the adenosine
      A1 receptor (A1R) antagonist - DPCPX - on depressive-like behavior in mice, as
      well as the effect of DPCPX on the activity of imipramine, escitalopram, and
      reboxetine, each at non-effective doses. The influence of DPCPX on behavior and
      its influence on the activity of selected antidepressants was evaluated in the
      forced swim test (FST) and the tail suspension test (TST) in mice. Locomotor
      activity was measured to verify and exclude false-positive data obtained in the
      FST and TST. Moreover, serum and brain concentrations of tested antidepressants
      were determined using HPLC. DPCPX, at doses of 2 and 4 mg/kg, exhibited
      antidepressant activity in the FST and TST, which was not related to changes in
      the spontaneous locomotor activity. Co-administration of DPCPX with imipramine,
      escitalopram, or reboxetine, each at non-active doses, significantly reduced the
      immobilization period in the FST and TST in mice, which was not due to the
      increase in locomotor activity. Both antagonists of 5-HT receptors (WAY 100635
      and ritanserin) completely antagonized the effect elicited by DPCPX in the
      behavioral tests. Results of assessment of the nature of the interaction between
      DPCPX and test drugs show that in the case of DPCPX and imipramine or reboxetine,
      there were pharmacodynamic interactions, whereas the DPCPX-escitalopram
      interaction is at least partially pharmacokinetic in nature. Presented outcomes
      indicate that an inhibition of A1Rs and an increase of monoaminergic transduction
      in the CNS may offer a novel strategy for the development of antidepressant
      drugs.

PMID- 30094463
TI  - Fifteenth Meeting of the Network Italiano per la Bioterapia dei Tumori (NIBIT) on
      Cancer Bio-Immunotherapy, Siena, Italy, October 5-7, 2017.

PMID- 30094465
TI  - BTBR ob/ob mouse model of type 2 diabetes exhibits early loss of retinal function
      and retinal inflammation followed by late vascular changes.
AB  - AIMS/HYPOTHESIS: Diabetic retinopathy is increasing in prevalence worldwide and
      is fast becoming a global epidemic and a leading cause of visual loss. Current
      therapies are limited, and the development of effective treatments for diabetic
      retinopathy requires a greater in-depth knowledge of disease progression and
      suitable modelling of diabetic retinopathy in animals. The aim of this study was
      to assess the early pathological changes in retinal morphology and neuronal,
      inflammatory and vascular features consistent with diabetic retinopathy in the
      ob/ob mouse model of type 2 diabetes, to investigate whether features similar to
      those in human diabetic retinopathy were present. METHODS: Male and female wild
      type (+/+), heterozygous (+/-) and homozygous (-/-) BTBR ob/ob mice were examined
      at 6, 10, 15 and 20 weeks of age. Animals were weighed and blood glucose was
      measured. TUNEL and brain-specific homeobox/POU domain protein 3A (BRN3A) markers
      were used to examine retinal ganglion cells. We used immunostaining (collagen IV
      and platelet endothelial cell adhesion molecule [PECAM]/CD31) to reveal retinal
      vessel degeneration. Spectral domain optical coherence tomography was used to
      reveal changes in the thickness and structure of the retinal layer. Vitreous
      fluorophotometry was used to investigate vascular permeability. A-waves, b-waves
      and oscillatory potentials were measured under photopic and scotopic conditions.
      Concanavalin A leucostasis and immunostaining with glial fibrillary acidic
      protein (GFAP) and ionised calcium-binding adapter molecule 1 (IBA-1) identified
      differences in inflammatory status. Paraffin sections and transmission electron
      microscopy were used to reveal changes in the thickness and structure of the
      retinal layer. RESULTS: Following the development of obesity and hyperglycaemia
      in 2-week-old and 3-week-old ob-/ob- mice, respectively (p < 0.001), early
      functional deficits (p < 0.001) and thinning of the inner retina (p < 0.001) were
      identified. Glial activation, leucostasis (p < 0.05) and a shift in
      microglia/macrophage phenotype were observed before microvascular degeneration (p
      < 0.05) and elevated vascular permeability occurred (p < 0.05).
      CONCLUSIONS/INTERPRETATION: The present characterisation of the development of
      diabetic retinopathy in the ob/ob mouse represents a platform that will enable
      the development of new therapies, particularly for the early stages of disease.

PMID- 30094466
TI  - Excess risk of hospitalisation for heart failure among people with type 2
      diabetes.
AB  - AIMS/HYPOTHESIS: Type 2 diabetes is an established risk factor for heart failure,
      but age-specific data are sparse. We aimed to determine excess risk of heart
      failure, based on age, glycaemic control and kidney function in comparison with
      age- and sex-matched control individuals from the general population. METHODS:
      Individuals with type 2 diabetes registered in the Swedish National Diabetes
      Registry 1998-2012 (n = 266,305) were compared with age-, sex- and county-matched
      control individuals without diabetes (n = 1,323,504), and followed over a median
      of 5.6 years until 31 December 2013. RESULTS: We identified 266,305 individuals
      with type 2 diabetes (mean age 62.0 years, 45.3% women) and 1,323,504 control
      individuals. Of the individuals with type 2 diabetes and control individuals,
      18,715 (7.0%) and 50,157 (3.8%) were hospitalised with a diagnosis of heart
      failure, respectively. Comparing individuals with diabetes with those in the
      control group, men and women with type 2 diabetes who were younger than 55 years
      of age had HRs for hospitalisation for heart failure of 2.07 (95% CI 1.73, 2.48)
      and 4.59 (95% CI 3.50, 6.02), respectively, using analyses adjusted for
      socioeconomic variables and associated conditions. Younger age, poorer glycaemic
      control and deteriorating renal function were all associated with increased
      excess risk of heart failure in those with type 2 diabetes compared with the
      control group. However, people with diabetes who were >=75 years and without
      albuminuria or with good glycaemic control (HbA1c <=52 mmol/mol [<=6.9%]) had a
      similar risk of hospitalisation for heart failure as control individuals in the
      same age group. CONCLUSIONS/INTERPRETATION: Men and women aged <55 years with
      type 2 diabetes are at markedly elevated excess risk of heart failure. The excess
      risk declined with age, but persisted even with good glycaemic control. However,
      among those who were 75 years and older, diabetic individuals with well
      controlled glucose levels or without albuminuria had a risk of heart failure that
      was on a par with individuals without diabetes.

PMID- 30094464
TI  - A clinical-pathogenetic approach on associated anomalies and chromosomal defects
      supports novel candidate critical regions and genes for gastroschisis.
AB  - BACKGROUND: Gastroschisis has been assumed to have a low rate of syndromic and
      primary malformations. We aimed to systematically review and explore the
      frequency and type of malformations/chromosomal syndromes and to identify
      significant biological/genetic roles in gastroschisis. METHODS: Population-based,
      gastroschisis-associated anomalies/chromosomal defects published 1950-2018
      (PubMed/MEDLINE) were independently searched by two reviewers. Associated
      anomalies/chromosomal defects and selected clinical characteristics were
      subdivided and pooled by race, system/region, isolated, and associated cases
      (descriptive analysis and chi-square test were performed). Critical regions/genes
      from representative chromosomal syndromes including an enrichment analysis using
      Gene Ontology Consortium/Panther Classification System databases were explored.
      Fisher's exact test with False Discovery Rate multiple test correction was
      performed. RESULTS: Sixty-eight articles and 18525 cases as a base were
      identified (prevalence of 17.9 and 3% for associated anomalies/chromosomal
      defects, respectively). There were 3596 associated anomalies, prevailing those
      cardiovascular (23.3%) and digestive (20.3%). Co-occurring anomalies were
      associated with male, female, American Indian, Caucasian, prenatally diagnosed,
      chromosomal defects, and mortality (P < 0.00001). Gene clusters on 21q22.11 and
      21q22.3 (KRTAP), 18q21.33 (SERPINB), 18q22.1 (CDH7, CDH19), 13q12.3 (FLT1),
      13q22.1 (KLF5), 13q22.3 (EDNRB), and 13q34 (COL4A1, COL4A2, F7, F10) were
      significantly related to biological processes: blood pressure regulation and/or
      vessel integrity, angiogenesis, coagulation, cell-cell and/or cell-matrix
      adhesion, dermis integrity, and wound healing (P < 0.05). CONCLUSIONS: Our
      findings suggest that gastroschisis may result from the interaction of several
      chromosomal regions in an additive manner as a pool of candidate genes were
      identified from critical regions supporting a role for vascular disruption,
      thrombosis, and mesodermal deficiency in the pathogenesis of gastroschisis.

PMID- 30094467
TI  - Toll-like receptor 9 negatively regulates pancreatic islet beta cell growth and
      function in a mouse model of type 1 diabetes.
AB  - AIMS/HYPOTHESIS: Innate immune effectors interact with the environment to
      contribute to the pathogenesis of the autoimmune disease, type 1 diabetes.
      Although recent studies have suggested that innate immune Toll-like receptors
      (TLRs) are involved in tissue development, little is known about the role of TLRs
      in tissue development, compared with autoimmunity. We aimed to fill the knowledge
      gap by investigating the role of TLR9 in the development and function of islet
      beta cells in type 1 diabetes, using NOD mice. METHODS: We generated Tlr9-/- NOD
      mice and examined them for type 1 diabetes development and beta cell function,
      including insulin secretion and glucose tolerance. We assessed islet and beta
      cell number and characterised CD140a expression on beta cells by flow cytometry.
      We also tested beta cell function in Tlr9-/- C57BL/6 mice. Finally, we used TLR9
      antagonists to block TLR9 signalling in wild-type NOD mice to verify the role of
      TLR9 in beta cell development and function. RESULTS: TLR9 deficiency promoted
      pancreatic islet development and beta cell differentiation, leading to enhanced
      glucose tolerance, improved insulin sensitivity and enhanced first-phase insulin
      secretory response. This was, in part, mediated by upregulation of CD140a (also
      known as platelet-derived growth factor receptor-alpha [PDGFRalpha]). In the
      absence of TLR9, induced by either genetic targeting or treatment with TLR9
      antagonists, which had similar effects on ontogenesis and function of beta cells,
      NOD mice were protected from diabetes. CONCLUSIONS/INTERPRETATION: Our study
      links TLR9 and the CD140a pathway in regulating islet beta cell development and
      function and indicates a potential therapeutic target for diabetes prevention
      and/or treatment.

PMID- 30094469
TI  - [Drug safety in pregnancy-a particular challenge].
AB  - Drug safety in pregnancy is of utmost importance because prenatal exposure to the
      unborn child may result in side effects with life-long consequences. Data on
      their risks in pregnancy are scarce for many drugs. Furthermore, there is often
      uncertainty how to translate risk data into practice.This article aims to
      identify tools to improve data ascertainment on exposed pregnancies and their
      outcome. Using the example of the German Embryotox institute, it is demonstrated
      how to disseminate drug safety knowledge to healthcare professionals and patients
      for clinical decision-making.Observational data are the most important basis for
      drug risk assessment in pregnancy. Such data are collected by Embryotox through
      the risk consultation process. Prospective cohort studies with comparison cohorts
      allow to estimate relative risks for birth defects, pregnancy loss, and other
      developmental anomalies. Retrospectively ascertained adverse drug reactions
      contribute to identification of distinct pattern of congenital anomalies.Drugs in
      pregnancy counselling require risk characterization dependent on the individual
      clinical setting: recommendation of treatment of choice (comparative risk
      assessment between effective drugs), individual risk estimation after
      (inadvertent) exposure, and assessment of causal relationship in cases of
      congenital anomalies. Combining counselling and protocols of pregnancy outcome
      after drug exposure is optimal to cost-efficiently ascertain data of high
      quality.Using acetaminophen, valproic acid, AT1-receptor blockers and retinoids
      as examples, recent discussions on drug risks in pregnancy and their clinical
      implications are presented.

PMID- 30094468
TI  - Reuse of bladder mucosa explants provides a long lasting source of urothelial
      cells for the establishment of differentiated urothelia.
AB  - Organ explant cultures are well-established in vitro models that are used to
      study normal cell biological and regeneration processes as well as
      carcinogenesis. Primary urothelial cultures from bladder mucosa explants are
      highly differentiated and are thus broadly used as in vitro experimental
      equivalents of native urothelial tissue. Since experiments on differentiated
      urothelial cultures from bladder mucosa explants currently allow only a single
      use of explants, establishment of sufficient quantities of cultures requires
      large numbers of sacrificed animals. There is thus a great need for a cheaper
      approach with less ethical dilemmas. Herein, we demonstrate that mouse bladder
      mucosa explants can be reused. Reused explants produce outgrowths with highly
      differentiated urothelia, just like primary explants. Even after being recycled
      ten times, urothelial outgrowths have the supramolecular and ultrastructural
      features that are comparable to the native urothelium. Ten times reused explants
      produce superficial urothelial cells that express uroplakins in the apical plasma
      membrane, claudin-8 in the tight junctions, and have a subapical network of
      cytokeratin 20. Basal urothelial cells in urothelial outgrowths of ten times
      reused explants express p63 which indicates that these urothelial outgrowths have
      a persistent proliferative capacity. Using our approach, one can perform
      experiments that were previously not feasible due to low quantities of donor
      tissue. The method also offers opportunity for effective use of scarce healthy
      human urothelial tissue.

PMID- 30094470
TI  - [Fostering medication safety by and for patients].
AB  - The overall goal of all measures for medication safety is the optimization of
      drug treatment and the prevention of unnecessary risk that potentially endangers
      patients. Per definition, the goal of medication safety is a beneficial patient
      outcome. Particularly in primary care, the success of many medication safety
      strategies will depend on the active participation of patients, as in this
      healthcare sector the patient is responsible for many substeps of the medication
      process.From a healthcare systems perspective, a number of medication safety
      strategies have been developed that aim to support the patient in their active
      role in the medication process. These strategies intend to safeguard the
      processes of care including transfer of information, but also aim to prevent
      intentional and unintentional nonadherence. The prerequisites for successful
      implementation are targeted awareness-raising measures to sensitize all
      participants for potential risks in the medication process. Moreover, readily
      available medication safety strategies must be easily accessible and promoted
      both to patients and healthcare providers.

PMID- 30094471
TI  - Electrocardiographic criteria of epicardial ventricular tachycardia with anterior
      origin.
AB  - BACKGROUND: ECG criteria for identifying an epicardial origin of ventricular
      tachycardia (VT) have mainly been described for VTs with basal-superior and
      lateral origin. OBJECTIVE: The aim of this study was to determine ECG criteria
      for epicardial VTs with anterior origin as a guide for trans-pericardial
      ablation. RESULTS: Among 22 patients undergoing successful ablation of VTs from
      the anterior myocardial wall, 14 patients underwent endocardial ablation and 8
      patients underwent epicardial ablation. VTs with anterior origin ablated
      epicardially had widened QS complexes in precordial leads with staircase-shaped
      notching and slowing of the descent to the nadir of S. In comparison, endocardial
      VTs with anterior origin usually had narrower QS complexes with a smooth and fast
      downstroke to the nadir of S. The duration of the negative pseudodelta wave was
      longer in epicardial VTs (55 +/- 12 ms) compared to endocardial VTs (22 +/- 12
      ms). The interval "time to the nadir of S" in patients with anterior VT origin
      was longer in epicardial VTs (121 +/- 16 ms) than in endocardial VTs (80 +/- 22
      ms). The QRS duration was also longer in patients with epicardial origin (212 +/-
      19 ms) than with endocardial VT origin (166 +/- 30 ms). CONCLUSIONS: Epicardial
      origin of VTs arising from the anterior myocardial wall produces a slowing,
      widening and staircase-shaped notching in the initial VT-QS complex. Thus, the
      morphology of the initial part of the QS complex in precordial leads can be used
      as a guide for trans-pericardial ablation of VTs with anterior origin.

PMID- 30094472
TI  - Polymer coatings based on sulfonated-poly-ether-ether-ketone films for implant
      dentistry applications.
AB  - Poly-ether-ether-ketone (PEEK) is one of the most important biocompatible
      polymers and its sulfonation has been studied for biomedical applications. The
      aim of the present study is to produce, to characterize and to assess bioactivity
      of PEEK coatings with sulfonated PEEK (SPEEK) films. Biomedical grade PEEK
      (Invibio(r), Batch: D0602, grade: NI1) was functionalized using sulfuric acid
      98%. SPEEK was dissolved into DMSO or into DMF, both at 10% mass/volume. PEEK
      bars (N = 18) and cylinders (N = 27) were manufactured by compression molding and
      heating. SPEEK/DMSO and SPEEK/DMF were drop casted at PEEK bars and dip coated at
      PEEK cylinders (PEEK + SPEEK/DMSO and PEEK + SPEEK/DMF). Characterization was
      performed through Fourier Transform Infrared Spectroscopy (FTIR), X-Ray
      Diffraction (XRD), Scanning Electron Microscope (SEM) and contact angle
      measurements. Bioactivity was assessed by immersion of samples at SBF for 1, 7
      and 21 days, followed by SEM, energy-dispersive analysis (EDX) and FTIR analysis.
      Statistical analysis was carried out by one-way analysis of variance (ANOVA) (p =
      0.05). Characteristic bands of PEEK and SPEEK, were identified through FTIR
      spectrum analysis, while semicrystallinity was confirmed by XRD. PEEK + SPEEK/DMF
      showed more evident physicochemical modifications. PEEK + SPEEK/DMSO provided a
      more regular and hydrophobic surface, observed through SEM and contact angle
      measurements. SEM/EDX showed that precipitates of calcium were formed at PEEK +
      SPEEK/DMSO and PEEK + SPEEK/DMF at all experimental times, but materials were not
      considered bioactive. Interesting surface properties were achieved with SPEEK
      coatings but the production of SPEEK films at PEEK surface has to be further
      improved and biologically tested. Schematic diagram showing the methodology
      applied in this study to prepare PEEK and SPEEK samples, as well as the promising
      application of the material.

PMID- 30094473
TI  - Activating transcription factor 3 in cardiovascular diseases: a potential
      therapeutic target.
AB  - Cardiovascular diseases (CVDs) are the primary causes of death worldwide. Among
      the numerous signaling molecules involved in CVDs, transcriptional factors
      directly influence gene expression and play a critical role in regulating cell
      function and the development of diseases. Activating transcription factor (ATF) 3
      is an adaptive-response gene in the ATF/cAMP responsive element-binding (CREB)
      protein family of transcription factors that acts as either a repressor or an
      activator of transcription via the formation of homodimers or heterodimers with
      other ATF/CREB members. A appropriate ATF3 expression is important for the normal
      physiology of cells, and dysfunction of ATF3 is associated with various
      pathophysiological responses such as inflammation, apoptosis, oxidative stress
      and endoplasmic reticulum stress, and diseases, including CVDs. This review
      focuses on the role of ATF3 in cardiac hypertrophy, heart failure,
      atherosclerosis, ischemic heart diseases, hypertension and diabetes mellitus to
      provide a novel therapeutic target for CVDs.

PMID- 30094474
TI  - Terahertz Electric Field-Induced Membrane Electroporation by Molecular Dynamics
      Simulations.
AB  - In this paper, the membrane electroporation induced by the terahertz electric
      field is simulated by means of the molecular dynamics method. The influences of
      the waveform and frequency of the applied terahertz electric field on the
      electroporation and the unique features of the process of the electroporation
      with the applied terahertz electric field are given. It shows that whether the
      electroporation can happen depends on the waveform of the applied terahertz
      electric field when the magnitude is not large enough. No pore appears if the
      terahertz electric field direction periodically reverses, and dipole moments of
      the interfacial water and the bulk water keep reversing. The nm-scale single pore
      forms with the applied terahertz trapezoidal electric field. It is found that the
      average pore formation time is strongly influenced by the terahertz electric
      field frequency. An abnormal variation region that shows decline exists on the
      correlation curve of the average pore formation time and the trapezoidal electric
      field frequency, whereas the overall trend of the curve is increasing. The
      decrease of the water oriented polarization degree results in the increase of the
      electroporation time, and the abnormal variation region appearance may be related
      to the drastic change of average water hydrogen bond number that is resulted from
      the resonance of water hydrogen bond network and the applied electric field.
      Compared to the nanosecond electric pulse and constant electric field, the
      numbers of the water protrusions and the water bridges are smaller and the pore
      formation time is relatively longer with the applied terahertz electric field.

PMID- 30094475
TI  - Mechanosensitivity of the BK Channels in Human Glioblastoma Cells: Kinetics and
      Dynamical Complexity.
AB  - BK channels are potassium selective and exhibit large single-channel conductance.
      They play an important physiological role in glioma cells: they are involved in
      cell growth and extensive migrating behavior. Due to the fact that these
      processes are accompanied by changes in membrane stress, here, we examine
      mechanosensitive properties of BK channels from human glioblastoma cells (gBK
      channels). Experiments were performed by the use of patch-clamp method on excised
      patches under membrane suction (0-40 mmHg) at membrane hyper- and depolarization.
      We have also checked whether channel's activity is affected by possible changes
      of membrane morphology after a series of long impulses of suction.
      Unconventionally, we also analyzed internal structure of the experimental signal
      to make inferences about conformational dynamics of the channel in stressed
      membranes. We examined the fractal long-range memory effect (by R/S Hurst
      analysis), the rate of changes in information by sample entropy, or correlation
      dimension, and characterize its complexity over a range of scales by the use of
      Multiscale Entropy method. The obtained results indicate that gBK channels are
      mechanosensitive at membrane depolarization and hyperpolarization. Prolonged
      suction of membrane also influences open-closed fluctuations-it decreases
      channel's activity at membrane hyperpolarization and, in contrary, increases
      channel's activity at high voltages. Both membrane strain and its "fatigue"
      reduce dynamical complexity of channel gating, which suggest decrease in the
      number of available open conformations of channel protein in stressed membranes.

PMID- 30094476
TI  - The History of Psoriatic Arthritis (PsA): From Moll and Wright to Pathway
      Specific Therapy.
AB  - PURPOSE OF REVIEW: Psoriatic arthritis is a distinct disorder, separate from
      rheumatoid arthritis, and first recognized in a thirteenth century Saxon
      skeleton. It was, however, the monumental work of Verna Wright in the 1950s that
      led to the acceptance by the American Rheumatism Association (now American
      College of Rheumatology) in 1964 as a distinct entity. Wright's work provided the
      framework for a better understanding of the pathogenic mechanisms operating on
      this condition, and eventually led to the development of targeted therapy that
      has proven to be more effective and safe than conventional therapy. RECENT
      FINDINGS: Pathogenesis of psoriatic arthritis has been better delineated in
      recent years, as well as the use of biological therapy. Recent findings are
      discussed in detail. Historical aspects of psoriatic arthritis, recent
      developments in pathogenesis, and therapy are discussed, and the contributions of
      Verna Wright to our understanding of the disorder are presented.

PMID- 30094477
TI  - Adenylyl cyclase 6 is involved in the hyposecretory status of experimental
      colitis.
AB  - One of the cardinal symptoms of intestinal inflammation is diarrhea. Acute
      intestinal inflammation is associated with inhibition of ion absorption and
      increased secretion, along with fluid leakage due to epithelial injury and
      changes in permeability. However, in the chronic situation, a downregulation of
      both absorptive and secretory transport has been reported. We investigated how
      experimental colitis reduces cAMP levels in intestinal epithelial cells through
      modulation of adenylyl cyclases (AC). Primary colonic epithelial cells obtained
      from rats with trinitrobenzenesulfonic acid colitis and non-colitic controls were
      analyzed for AC expression by RT-qPCR and Western blot, following a preliminary
      microarray analysis. AC6 and AC5 were found to be expressed in colonocytes, and
      downregulated by inflammation, with the former exhibiting considerably higher
      mRNA levels in both cases. To test the hypothesis that inflammatory cytokines may
      account for this effect, Caco 2 cells were treated with IL-1beta, TNF-alpha, or
      IFN-gamma. All three cytokines inhibited forskolin evoked short-circuit currents
      in Ussing chambers and lowered intracellular cAMP, but failed to alter AC6 mRNA
      levels. AC5/AC6 expression was however inhibited in mouse jejunal organoids
      treated with IFN-gamma and TNF-alpha, but not IL-1beta. Gene knockdown of AC6
      resulted in a significant decrease of ion secretion in T84 cells. We conclude
      that the disturbances in ion secretion observed in rat TNBS colitis are
      associated with low intracellular levels of cAMP in the epithelium, which may be
      explained in part by the downregulation of AC5/AC6 expression by proinflammatory
      cytokines.

PMID- 30094478
TI  - Electroacupuncture induces antihyperalgesic effect through endothelin-B receptor
      in the chronic phase of a mouse model of complex regional pain syndrome type I.
AB  - Complex regional pain syndrome (CRPS) is a disorder that involves abnormal
      inflammation and nerve dysfunction frequently resistant to a broad range of
      treatments. Peripheral nerve stimulation with electroacupuncture (EA) has been
      widely used in different clinical conditions to control pain and inflammation;
      however, the use of EA in the treatment of CRPS is under investigation. In this
      study, we explore the effects of EA on hyperalgesia and edema induced in an
      animal model of chronic post-ischemia pain (CPIP model) and the possible
      involvement of endothelin receptor type B (ETB) in this effect. Female Swiss mice
      were subjected to 3 h hind paw ischemia/reperfusion CPIP model. EA treatment
      produced time-dependent inhibition of mechanical and cold hyperalgesia, as well
      as edema in CPIP mice. Peripheral administration (i.pl.) of BQ-788 (10 nmol), an
      ETB antagonist, prevented EA-induced antihyperalgesia while intrathecal
      administration prolonged EA's effect. Additionally, peripheral pre-treatment with
      sarafotoxin (SRTX S6c, 30 pmol, ETB agonist) increased EA anti-hyperalgesic
      effect. Furthermore, the expression of peripheral ETB receptors was increased
      after EA treatments, as measured by western blot. These results may suggest that
      EA's analgesic effect is synergic with ETB receptor activation in the periphery,
      as well as central (spinal cord) ETB receptor blockade. These data support the
      use of EA as a nonpharmacological approach for the management of CRPS-I, in an
      adjuvant manner to ETB receptor targeting drugs.

PMID- 30094479
TI  - [Isolated iliac artery aneurysms : Interventional treatment].
AB  - CLINICAL ISSUE: Isolated iliac artery aneurysms occur considerably less often
      than abdominal aortic aneurysms. Mainly older men are affected by this disease.
      Most of these aneurysms are asymptomatic and are incidentally detected during
      cross-sectional imaging. Iliac aneurysms with a diameter larger than 3 cm are at
      risk for rupture, which is associated with high morbidity and mortality. STANDARD
      TREATMENT: To prevent their rupture as well as for symptomatic or ruptured
      aneurysms, endovascular treatment has recently been established as the primary
      approach due to the decreased morbidity and mortality compared to open repair.
      Endovascular aneurysm exclusion is performed with stent grafts, and depending on
      the anatomy, by adjunctive internal iliac artery embolization. TREATMENT
      INNOVATIONS: Up to a quarter of treated patients will require additional
      endovascular revisions during the long term. Reliable imaging follow-up likely
      increases the safety of elective or emergent endovascular iliac artery aneurysm
      repair.

PMID- 30094480
TI  - [Aortic bifurcation reconstruction : Endovascular repair and alternatives].
AB  - CLINICAL ISSUE: Aortic bifurcation disease is a manifestation of arteriosclerosis
      in about 95% of cases. Stenotic disease of the aortic bifurcation is a special
      form of peripheral arterial occlusive disease (PAOD). Men older than 60 years are
      particularly affected. STANDARD TREATMENT: The potential of endovascular therapy
      has continued to increase. Hereby, the increased availability of hybrid operating
      suites which allow for a combined use of endovascular techniques and open surgery
      plays an important role. DIAGNOSTIC WORK-UP: For the decision on the type of
      therapy and the sizing of the prosthesis, thin-slice CT angiography (CTA) of the
      abdominal aorta and the iliac arteries including multiplanar reconstructions in
      the sagittal and coronal planes is sufficient. The inguinal arteries have to be
      included in the CTA volume. PERFORMANCE: Compared to open surgery, endovascular
      therapy of aortic bifurcation disease has the advantage of reduced invasiveness.
      ACHIEVEMENTS: Treatment of aortic bifurcation disease continues to change. In
      daily practice, the standard treatment of complex aortic bifurcation disease is
      still open surgery. However, an increasing number of studies indicate that
      endovascular therapy and open surgery should be considered equivalent,
      complementary methods. PRACTICAL RECOMMENDATIONS: Good quality preinterventional
      CTA is important for intervention planning. If you want to offer endovascular
      therapy as a radiologist, knowledge of interventional skills and close
      cooperation with clinical colleagues, particularly the vascular surgeon, is
      mandatory.

PMID- 30094481
TI  - Threats to Belonging, Immune Function, and Eating Behavior: an Examination of Sex
      and Gender Differences.
AB  - PURPOSE OF REVIEW: The first goal of this review is to discuss the evidence
      linking belonging threats to immune function and food intake. The second goal is
      to evaluate whether the links among belonging threats, immune function, and
      eating behavior differ based on gender. RECENT FINDINGS: Threats to belonging are
      linked to elevated herpesvirus antibody titers, dysregulated appetite-relevant
      hormones, and increased food consumption. Furthermore, these relationships are
      largely consistent for both men and women. Threats to belonging are also linked
      to elevated inflammation. However, some studies showed that these effects were
      stronger among women, others demonstrated that they were stronger among men, and
      others determined that the links were consistent for men and women. Understanding
      why belonging threats are inconsistently linked to inflammation across men and
      women is an important next step. We conclude the review with four concrete
      recommendations for researchers studying belonging threats, immune function, and
      eating behavior.

PMID- 30094482
TI  - Underemployment, overemployment and deterioration of mental health: the role of
      job rewards.
AB  - OBJECTIVES: Working more (overemployment) or less (underemployment) than
      preferred has been associated with poor mental health in cross-sectional studies,
      but longitudinal evidence is scarce. We investigate whether under- and
      overemployment is associated with 2-year changes of mental health and whether
      associations vary by job rewards (i.e. high earnings, job security, promotion
      prospects and occupational prestige). METHODS: We used two waves of the German
      Socio-Economic Panel (GSOEP), with information on mental health collected in 2006
      and 2008. Workers in paid employment (3266 men and 3139 women) who did not change
      jobs between 2006 and 2008, aged 20-60 years were selected. Under- and
      overemployment was assessed using the discrepancy between the actual and
      preferred working hours. Mental health was assessed using the Mental Component
      Summary (MCS) score, a subscale from the Short Form 12 Health Survey. Questions
      on rewards at work were added and divided into tertiles. Conditional change
      models were estimated to predict change in MCS. RESULTS: Findings indicate that
      overemployment and low reward at work (for men and women) were linked to a
      reduction in mental health. Underemployment was not related to a reduction in
      mental health. Albeit associations between under-/overemployment and mental
      health slightly differed across levels of reward, interactions did not reach
      statistical significance. CONCLUSIONS: Our findings demonstrate that
      overemployment was related to negative mental health change, and that this
      relationship held true both for people with high and with low reward at work.

PMID- 30094483
TI  - [Borderline personality : Alterations to brain structure and function through
      psychotherapy].
AB  - BACKGROUND: There are now several scientifically evaluated psychotherapeutic
      methods for borderline personality disorder (BPD), all of which aim to improve
      the ability to regulate emotions. In recent years, there have been first studies
      on the neuronal correlates of the mechanisms of emotion regulation and of changes
      caused by psychotherapeutic interventions. METHODS: This article reviews the data
      on functional and structural imaging studies that examine facets of disturbed
      emotion regulation before and after psychotherapy. RESULTS: Although the overall
      database is still sparse, clinical improvement in psychotherapy appears to be
      associated with modulation of brain structure and function. Frontolimbic
      regulation circuits including the amygdala, insula, anterior cingulate cortex
      (ACC) and other prefrontal areas appear to be involved in these changes. An
      important finding is the reduction of initially increased amygdala activity after
      successful Dialectical Behavior Therapy (DBT). CONCLUSION: The changes shown here
      most probably reflect an improvement in emotion regulation capacities in BPD and
      demonstrate the possibility of modulating disturbed emotion regulation processes.
      Since long-term follow-up data are still missing, the sustainability of the
      suggestive improvements still has to be proven in further studies.

PMID- 30094484
TI  - Breast Cancers of Special Histologic Subtypes Are Biologically Diverse.
AB  - BACKGROUND/OBJECTIVE: Cancers classified as "special histologic subtypes" are
      felt to have a good prognosis. We used the 21-gene Oncotype DX Breast Recurrence
      Score(r) multigene assay to examine prognostic variation within special
      histologic subtypes. We also examined the Recurrence Score(r) (RS) distribution
      among the more common ductal (IDC) and lobular (ILC) cancers. METHODS: 610,350
      tumor specimens examined in the Genomic Health clinical laboratory from 2/2004 to
      8/2017 were included. Specimen histology was classified centrally using a single
      H&E slide and World Health Organization criteria. RS distribution (low < 18,
      intermediate 18-30, and high >= 31) was compared among histologic subtypes.
      RESULTS: Median patient age was 60 years (IQR 51-67); 80% were node negative.
      Most patients had low RS results (59.2%); only 9.5% had high results. The lowest
      mean RS was seen in the papillary subtype (11); the highest in the IDC group
      (18.4). Mean RS for all special subtypes was lower than that of IDC patients.
      When the high RS threshold was decreased from 31 to 25, as used in the TAILORx
      and RxPONDER trials, the number of high RS-result patients increased from 9.5% to
      16.8%. Patients with ILC had a lower mean RS result than patients with IDC, 16.5
      versus 18.4. CONCLUSION: There is substantial diversity in predicted prognosis
      among patients with cancers classified as special histologic subtypes, with 12
      25% having intermediate RS results and 0.5-9% having high RS results. Pending
      further definition of the role of chemotherapy for patients with intermediate RS
      results by TAILORx and RxPONDER, the RS result may help to inform systemic
      therapy decisions in these patients.

PMID- 30094485
TI  - Analysis of GJB2 mutations and the clinical manifestation in a large Hungarian
      cohort.
AB  - PURPOSE: Pathogenic variants of the gap junction beta 2 (GJB2) gene are
      responsible for about 50% of hereditary non-syndromic sensorineural hearing loss
      (NSHL). In this study, we report mutation frequency and phenotype comparison of
      different GJB2 gene alterations in Hungarian NSHL patients. METHODS: The total
      coding region of the GJB2 gene was analyzed with Sanger or NGS sequencing for 239
      patients with NSHL and 160 controls. RESULTS: Homozygous and compound
      heterozygous GJB2 mutations were associated with early onset serious clinical
      phenotype in 28 patients. In 24 patients, two deletion or nonsense mutations were
      detected in individuals with mainly prelingual NSHL. In compound heterozygous
      cases, a combination of deletion and missense mutations associated with milder
      postlingual NSHL. A further 25 cases harbored single heterozygous GJB2 mutations
      mainly associated with later onset, milder clinical phenotype. The most common
      mutation was the c.35delG deletion, with 12.6% allele frequency. The hearing loss
      was more severe in the prelingual groups. CONCLUSION: The mutation frequency of
      GJB2 in the investigated cohort is lower than in other European cohorts. The most
      serious cases were associated with homozygous and compound heterozygous
      mutations. In our cohort the hearing impairment and age of onset was not altered
      between in cases with only one heterozygous GJB2 mutation and wild type genotype,
      which may exclude the possibility of autosomal dominant inheritance. In early
      onset, severe to profound hearing loss cases, if the GJB2 analysis results in
      only one heterozygous alteration further next generation sequencing is highly
      recommended.

PMID- 30094487
TI  - Nuts and Cardiovascular Disease Prevention.
AB  - PURPOSE OF REVIEW: We review recent epidemiological and clinical studies
      investigating the consumption of tree nuts and peanuts and cardiovascular disease
      (CVD) mortality as well as CVD risk factors. RECENT FINDINGS: A greater
      consumption of tree nuts and peanuts is associated with a reduced risk of CVD
      mortality, as well as lower CVD events. Furthermore, risk factors associated with
      the development of CVD such as dyslipidemia, impaired vascular function, and
      hypertension are improved with regular tree nut and peanut consumption through a
      range of mechanism associated with their nutrient-rich profiles. There is weak
      inconsistent evidence for an effect of nut consumption on inflammation. There is
      emerging evidence that consuming tree nuts reduces the incidence of non-alcoholic
      fatty liver disease (NAFLD) and promotes diversity of gut microbiota, which in
      turn may improve CVD outcomes. Evidence for CVD prevention is strong for some
      varieties of tree nuts, particularly walnuts, and length of supplementation and
      dose are important factors for consideration with recommendations.

PMID- 30094489
TI  - Grapevine leafroll disease alters leaf physiology but has little effect on plant
      cold hardiness.
AB  - MAIN CONCLUSION: Foliar sugar accumulation in grapevines with leafroll disease
      was correlated with lower photosynthesis, likely due to feedback inhibition.
      However, cold acclimation of dormant tissues remained unaffected by the virus
      status. Grapevine leafroll-associated viruses (GLRaV) contribute to losses in
      fruit yield and quality worldwide. Visually, leafroll disease symptoms appear
      similar to those associated with an imbalance in source/sink relations and a
      concomitant feedback inhibition of photosynthesis, which is often caused by an
      impasse in sugar translocation. In order to test this potential relationship and
      related physiological responses, leaf water status, gas exchange, non-structural
      carbohydrates, and dormant tissue cold hardiness were examined over 2 years in
      healthy and GLRaV-3-infected, field-grown Merlot grapevines. Diurnal and seasonal
      changes in leaf water status and gas exchange were dominated by variations in
      water availability, temperature, and leaf age, while GLRaV-3 infection
      contributed less to the overall variation. By contrast, foliar carbohydrates
      increased markedly in infected plants, with starch accumulating early in the
      growing season, followed by soluble sugar accumulation, leaf reddening, and
      declining gas exchange. Photosynthesis correlated negatively with leaf sugar
      content. However, dormant-season cold hardiness of buds and cane vascular tissues
      was similar in healthy and infected vines. These findings support the idea that
      visible symptoms of grapevine leafroll disease are a consequence of carbohydrate
      accumulation which, in turn, may lead to feedback inhibition of photosynthesis.
      In addition, this study provided evidence that GLRaV-3 infection is unlikely to
      alter the susceptibility to moderate water deficit and winter damage in mature
      Merlot grapevines.

PMID- 30094488
TI  - Sugar transport played a more important role than sugar biosynthesis in fruit
      sugar accumulation during Chinese jujube domestication.
AB  - MAIN CONCLUSION: Sugar transport, including the symplasmic pathway in
      plasmodesmata and apoplasmic pathway mediated by sugar transporters, accelerated
      sugar accumulation in cultivated jujube, while sugar metabolism-related genes
      played weak roles in jujube domestication. The fruit of Chinese jujube (Ziziphus
      jujuba Mill.) is high in sugar concentration. By contrast, wild type-sour jujube
      (Z. jujuba Mill. var. spinosa Hu) contains markedly less sugar. It is unknown
      whether sugar transport or sugar metabolism drove sugar accumulation during
      jujube domestication. Using a combination of ultrastructural observations,
      phylogenetic analysis, testing for soluble sugars, and transcriptional analysis,
      the sugar accumulation mechanism was studied in the developmental stages of
      cultivated jujube and sour jujube. Our results indicate that the symplasmic
      transport pathway in plasmodesmata is present in cultivated jujube, but not in
      sour jujube. Sugar transporter genes have higher frequencies of duplication than
      sugar metabolism-related genes. Gene expression patterns indicate that sugar
      transporter genes, especially ZjSUT2, ZjSWEET1, ZjSWEET7, ZjSWEET11, ZjSTP3, and
      ZjSTP13a, rather than sugar metabolism-related genes showed higher expression
      levels in cultivated jujube versus sour jujube during fruit sugar accumulation.
      These findings suggest that sugar transport, including apoplasmic and symplasmic
      transport, rather than sugar biosynthesis, is associated with the difference in
      sugar accumulation between jujube and sour jujube, and that it may drive jujube
      domestication. This study provides valuable genetic information for jujube
      improvement, and offers new insights into fruit tree domestication related to
      sugar accumulation.

PMID- 30094486
TI  - Approach to cervicogenic dizziness: a comprehensive review of its aetiopathology
      and management.
AB  - PURPOSE: Though there is abundant literature on cervicogenic dizziness with at
      least half a dozen of review articles, the condition remains to be enigmatic for
      clinicians dealing with the dizzy patients. However, most of these studies have
      studied the cervicogenic dizziness in general without separating the constitute
      conditions. Since the aetiopathological mechanism of dizziness varies between
      these cervicogenic causes, one cannot rely on the universal conclusions of these
      studies unless the constitute conditions of cervicogenic dizziness are separated
      and contrasted against each other. METHODS: This narrative review of recent
      literature revisits the pathophysiology and the management guidelines of various
      conditions causing the cervicogenic dizziness, with an objective to formulate a
      practical algorithm that could be of clinical utility. The structured discussion
      on each of the causes of the cervicogenic dizziness not only enhances the
      readers' understanding of the topic in depth but also enables further research by
      identifying the potential areas of interest and the missing links. RESULTS:
      Certain peculiar features of each condition have been discussed with an emphasis
      on the recent experimental and clinical studies. A simple aetiopathological
      classification and a sensible management algorithm have been proposed by the
      author, to enable the identification of the most appropriate underlying cause for
      the cervicogenic dizziness in any given case. However, further clinical studies
      are required to validate this algorithm. CONCLUSIONS: So far, no single clinical
      study, either epidemiological or interventional, has incorporated and isolated
      all the constitute conditions of cervicogenic dizziness. There is a need for such
      studies in the future to validate either the reliability of a clinical test or
      the efficacy of an intervention in cervicogenic dizziness.

PMID- 30094491
TI  - Discriminant value of IEL counts and distribution pattern through the spectrum of
      gluten sensitivity: a simple diagnostic approach.
AB  - Intraepithelial lymphocytosis (IELosis) with or without villous abnormality is a
      characteristic feature of gluten sensitivity (GS) including celiac disease (CD)
      and non-celiac-GS, although various conditions may also be associated with
      IELosis. In order to distinguish GS from the other causes of IELosis, a threshold
      for IEL counts is necessary. We aimed to determine a cut-off value for IELs and
      monitor its value in the spectrum of GS in a large cohort. For this purpose, the
      duodenal biopsies from four groups of individuals including Types 1 (n = 88) and
      3 (n = 92) CD, non-CD IELosis (n = 112), and control (n = 82) cases, all strictly
      defined by their clinical, laboratory, and serologic features, were evaluated.
      The number of IELs/100 enterocytes and their distribution pattern on H&E- and CD3
      immunostained sections were assessed for each group. Kruskal-Wallis test and ROC
      curve analysis for discriminant value were employed for statistics. The IEL
      counts showed an increasing trend through the spectrum of mucosal pathology
      including controls (12.06; 21.40), non-CD IELosis (28.62; 39.46), Type 1 CD
      (49.27; 60.15), and Type 3 CD (58.53; 71.74) both on H&E- and CD3-immunostained
      sections, respectively (p < 0.001). ROC analysis revealed 20.5 on H&E and 28.5 on
      CD3 as the IEL cut-off values with a sensitivity of 95.9 and 87.7% and a
      specificity of 98.8% and 93.9%, respectively, for controls. IELs showed a diffuse
      distribution pattern per biopsy piece and per villus (90.9%, 100%, respectively)
      in nearly all of Type 1 CD cases (p < 0.001). An IEL cut-off value of 20.5 on H&E
      together with a diffuse distribution pattern seem to be the most discriminant
      features for the diagnosis of CD, even for the milder forms of the disease.

PMID- 30094490
TI  - Response of cell-wall composition and RNA-seq transcriptome to methyl-jasmonate
      in Brachypodium distachyon callus.
AB  - MAIN CONCLUSION: Methyl-jasmonate induces large increases in p-coumarate linked
      to arabinoxylan in Brachypodium and in abundance of GT61 and BAHD family
      transcripts consistent with a role in synthesis of this linkage. Jasmonic acid
      (JA) signalling is required for many stress responses in plants, inducing large
      changes in the transcriptome, including up-regulation of transcripts associated
      with lignification. However, less is known about the response to JA of grass cell
      walls and the monocot-specific features of arabinoxylan (AX) synthesis and
      acylation by ferulic acid (FA) and para-coumaric acid (pCA). Here, we show that
      methyl-jasmonate (MeJA) induces moderate increases in FA monomer, > 50% increases
      in FA dimers, and five-sixfold increases in pCA ester-linked to cell walls in
      Brachypodium callus. Direct measurement of arabinose acylated by pCA (Araf-pCA)
      indicated that most or all the increase in cell-wall pCA was due to pCA ester
      linked to AX. Analysis of the RNA-seq transcriptome of the callus response showed
      that these cell-wall changes were accompanied by up-regulation of members of the
      GT61 and BAHD gene families implicated in AX decoration and acylation; two BAHD
      paralogues were among the most up-regulated cell-wall genes (seven and fivefold)
      after 24 h exposure to MeJA. Similar responses to JA of orthologous BAHD and GT61
      transcripts are present in the RiceXPro public expression data set for rice
      seedlings, showing that they are not specific to Brachypodium or to callus. The
      large response of AX-pCA to MeJA may, therefore, indicate an important role for
      this linkage in response of primary cell walls of grasses to JA signalling.

PMID- 30094495
TI  - Cauda equina syndrome in a patient diagnosed with type 1 Gaucher disease: a rare
      case.
AB  - BACKGROUND: Gaucher disease is a rare hereditary glycolipid storage disease. One
      of the rare complications is neurodeficits due to vertebral involvement. CASE
      PRESENTATION: An 18-year-old female patient presented to the outpatient clinic
      with cauda equina syndrome due to sacral involvement of type 1 GD. Bilateral
      laminectomy via posterior approach without posterior stabilization was performed.
      CONCLUSION: Maximum excision of the mass avoiding destabilization of the spinal
      column can provide long-term vertebral stability and improvement in
      neurodeficits.

PMID- 30094494
TI  - Endovascular management of a giant petrous internal carotid artery aneurysm in a
      child. Case report and literature review.
AB  - BACKGROUND: Aneurysms of the petrosal segment of the internal carotid artery are
      rare in children and are usually found secondary to trauma and infection or can
      have a congenital origin. Management includes endovascular therapy, surgery, and
      in rare cases observation. DISCUSSION: Here, we report our experience with a
      giant petrous internal carotid artery aneurysm in a 16-year-old boy successfully
      managed endovascularly by parent artery occlusion.

PMID- 30094492
TI  - Dual staining for p16/Ki67 is a more specific test than cytology for triage of
      HPV-positive women.
AB  - Globally, cervical cancer (CC) screening is moving from cytology-based to HPV
      screening or a combination of both (co-testing). Most HPV-positive women clear
      the virus and do not develop relevant disease. Additional triage approaches are
      needed to reduce unnecessary colposcopy referrals. The p16/Ki67 dual stain
      cytology test (DSCT) is one of the most promising, but it has not (yet) been
      included as a recommendation in European guidelines. Previous studies in Spain on
      this issue are lacking. We studied the performance of p16/Ki67 DSCT for the
      triage of HPV-positive women in Navarra to detect precursor lesions (PLs) and CC
      compared to cytology only. We selected 1865 HPV-positive women with p16/Ki67 DSCT
      results and 304 women with an available biopsy result. Sensitivity, specificity
      and predictive values of the p16/Ki67 DSCT to detect underlying PLs and CC
      compared to cytology were calculated, using the biopsy as the gold standard.
      Cytology and p16/Ki67 DSCT showed similar sensitivity (99.0% vs. 98.0%), but
      cytology had significantly lower specificity (6.9 vs. 39.1%). Of the CIN2+/HPV+
      women, triage using cytology only would have resulted in 40.2% true PLs and CC,
      while using p16/Ki67 DSCT this was 98.0% qualifying the women for colposcopy
      referral. Our results show that p16/Ki67 DSCT detects more than twice as many
      true PLs and CC than cytology only in this population. Thus, this test can be
      considered as an important additional tool in HPV testing-based screening
      strategies, to avoid unnecessary colposcopy referrals and to reduce health care
      costs.

PMID- 30094496
TI  - Sir Richard Owen (1804-1892) and his work on the developing skull.

PMID- 30094493
TI  - Activating human epidermal growth factor receptor 2 (HER2) gene mutation in bone
      metastases from breast cancer.
AB  - In addition to amplification, point mutations of the human epidermal growth
      factor receptor 2 (HER2) gene (ERBB2) have been shown to activate the
      corresponding signaling pathway in breast cancer. The prevalence of ERBB2/HER2
      mutation in bone metastasis of breast cancer and the associated phenotype are not
      known. In this study, bone metastases from breast cancer patients (n = 231) were
      analyzed for ERBB2/HER2 mutation. In 7 patients (3%; median age 70 years, range
      50-83 years), gain-of-function mutations of ERBB2/HER2 were detected. The most
      frequent mutation was p.L755S (71%). In 29% of mutated cases, p.V777L was found.
      Lobular breast cancer was present in 71% of mutated cases (n = 5) and in 49% of
      all samples (n = 231; p = 0.275). Mutation frequency was 4.4% in the lobular
      subgroup and 17.4% in the pleomorphic subtype of lobular cancer (n = 23),
      respectively. All but one mutated lobular cancers were of the pleomorphic subtype
      (p = 0.006). Mutated cancers belonged either to the luminal (n = 4) or to the
      triple-negative types (n = 3). With regard to protein expression and gene
      amplification, HER2 was negative in all mutated cases. Among the 14% of
      metastatic luminal cancers with estrogen receptor gene (ESR1) mutation, conveying
      resistance against aromatase inhibitors, no concomitant ERBB2/HER2 mutation
      occurred. We conclude that activating HER2 mutation is present in about 3% of
      bone metastases from breast cancers, with significantly higher rates in the
      pleomorphic subtype of lobular cancer. Since mutated cases appear to be HER2
      negative by conventional testing, the opportunity for specific anti-HER2 therapy
      may be missed.

PMID- 30094498
TI  - Posterior capsular release is a biomechanically safe procedure to perform in
      total knee arthroplasty.
AB  - PURPOSE: Surgeons may attempt to strip the posterior capsule from its femoral
      attachment to overcome flexion contracture in total knee arthroplasty (TKA);
      however, it is unclear if this impacts anterior-posterior (AP) laxity of the
      implanted knee. The aim of the study was to investigate the effect of posterior
      capsular release on AP laxity in TKA, and compare this to the restraint from the
      posterior cruciate ligament (PCL). METHODS: Eight cadaveric knees were mounted in
      a six degree of freedom testing rig and tested at 0 degrees , 30 degrees , 60
      degrees  and 90 degrees  flexion with +/- 150 N AP force, with and without a 710
      N axial compressive load. After the native knee was tested, a deep dished
      cruciate-retaining TKA was implanted and the tests were repeated. The PCL was
      then cut, followed by releasing the posterior capsule using a curved osteotome.
      RESULTS: With 0 N axial load applied, cutting the PCL as well as releasing the
      posterior capsule significantly increased posterior laxity compared to the native
      knee at all flexion angles, and CR TKA states at 30 degrees , 60 degrees  and 90
      degrees  (p < 0.05). However, no significant increase in laxity was found between
      cutting the PCL and subsequent PostCap release (n.s.). In anterior drawer, there
      was a significant increase of 1.4 mm between cutting the PCL and PostCap release
      at 0 degrees , but not at any other flexion angles (p = 0.021). When a 710 N
      axial load was applied, there was no significant difference in anterior or
      posterior translation across the different knee states (n.s.). CONCLUSIONS:
      Posterior capsular release only caused a small change in AP laxity compared to
      cutting the PCL and, therefore, may not be considered detrimental to overall AP
      stability if performed during TKA surgery. LEVEL OF EVIDENCE: Controlled
      laboratory study.

PMID- 30094497
TI  - Flexed femoral component improves kinematics and biomechanical effect in
      posterior stabilized total knee arthroplasty.
AB  - PURPOSE: The kinematics and biomechanics of the knee joint are important in
      ensuring patient satisfaction and functional ability after total knee
      arthroplasty (TKA). There has been no study on knee joint mechanics with regard
      to the sagittal alignment of the femoral component. The objective of this study
      is to determine the extent of the impact of the femoral component's sagittal
      alignment on kinematics and biomechanics. METHODS: A validated computational TKA
      model was used. The femoral component was simulated at - 3 degrees , 0 degrees ,
      5 degrees , and 7 degrees  of flexion in the sagittal plane. This study evaluated
      the tibiofemoral (TF) joint kinematics, contact point, quadriceps force, and
      contact stress on the patellofemoral (PF) joint under a deep-knee-bend condition.
      RESULTS: The kinematics of the TF joint in the posterior direction increased with
      the flexion of the femoral component position. For all tasks, the overall
      posterior locations of the TF contact points were observed in the medial and
      lateral compartments as the femoral component flexion angle increased. The
      quadriceps force and contact stress on the PF joint decreased with the femoral
      component flexion. CONCLUSION: This study found that the femoral component
      sagittal position is an important factor in knee joint mechanics. In this study,
      the flexion of femoral component showed a stable reconstruction of the knee
      extensors' mechanism. Surgeons may consider neutral-to-mild flexed femoral
      component position, without concerns of anterior notching of the femoral cortex.

PMID- 30094499
TI  - Depression and glioblastoma, complicated concomitant diseases: a systemic review
      of published literature.
AB  - Glioblastoma multiforme (GBM) is the most common primary brain cancer. Depression
      is a common co-morbidity of this condition. Despite this common interaction,
      relatively little research has been performed on the development of GBM
      associated depression. We performed a literary search of the PubMed database for
      articles published relating to GBM and depression. A total of 85 articles were
      identified with 46 meeting inclusion criteria. Depression significantly impacts
      care, decreasing medication compliance, and patient survival. Diagnostically,
      because depression and GBM share intricate neuro-connectivity in a way that
      effect functionality, these diseases can be mistaken for alternative
      psychological or pathological disorders, complicating care. Therapeutically, anti
      depressants have anti-tumor properties; yet, some have been shown to interfere
      with GBM treatment. One reason for this is that the pathophysiological
      development of depression and GBM share several pathways including altered
      regulation of the 5-HT receptor, norepinephrine, and 3':5'-cyclic monophosphate.
      Over time, depression can persist after GBM treatment, affecting patient quality
      of life. Together, depression and GBM are complicated concomitant diseases.
      Clinicians must be aware of their co-existence. Because of overlapping molecular
      pathways involved in both diseases, careful medication selection is imperative to
      avoid potential adverse interactions. Since GBMs are the most common primary
      brain cancer, physicians dealing with this disease should be prepared for the
      development of depression as a potential sequela of this condition, given the
      related pathophysiology and the known poor outcomes.

PMID- 30094500
TI  - Correction to: Acute phenylalanine/tyrosine depletion of phasic dopamine in the
      rat brain.
AB  - After publication of this paper, the authors determined an error in the
      calculation of the norepinephrine standard concentrations for the HPLC
      calibration curves.

PMID- 30094501
TI  - Design, synthesis, and in silico studies of novel eugenyloxy propanol azole
      derivatives having potent antinociceptive activity and evaluation of their beta
      adrenoceptor blocking property.
AB  - The design, synthesis, antinociceptive and beta-adrenoceptor blocking activities
      of several eugenyloxy propanol azole derivatives have been described. In this
      synthesis, the reaction of eugenol with epichlorohydrin provided adducts 3 and 4
      which were N-alkylated by diverse azoles to obtain the eugenyloxy propanol azole
      analogues in good yields. Adducts 3 and 4 were also reacted with azide ion to
      obtain the corresponding azide 6. The 'Click' Huisgen cycloaddition reaction of 6
      with diverse alkynes afforded the title compounds in good yields. The synthesized
      eugenyloxy propanol azole derivatives were in vivo studied for the acute
      antinociception on male Spargue Dawley rats using tail-flick test. Compounds 5f,
      5g, 7b and 11a exhibited potent analgesic properties in comparison with eugenol
      as a standard drug. In addition, all compounds were ex vivo tested for beta
      adrenoceptor blocking properties on isolated left atrium of male rats which
      exhibited partial antagonist or agonist behaviour compared to the standard drugs.
      The molecular docking study on the binding site of transient receptor potential
      vanilloid subtype 1 (TRPV1) has indicated that like capsaicin, eugenyloxy
      propanol azole analogues exhibited the strong affinity to bind at site of TPRV1
      in a "tail-up, head-down" conformation and the presence of triazolyl moieties has
      played undeniable role in durable binding of these ligands to TRPV1. The in
      silico pharmacokinetic profile, drug likeness and toxicity predictions carried
      out for all compounds determined that 5g can be considered as potential
      antinociceptive drug candidate for future research.

PMID- 30094503
TI  - [Diagnosis and stage-adapted treatment of acute pancreatitis].
AB  - Acute pancreatitis is a potentially life-threatening disease, which is
      morphologically classified into interstitial edematous or necrotizing
      pancreatitis. According to the revised Atlanta classification, mild, moderate and
      severe clinical courses are differentiated regarding local and systemic
      complications as well as concomitant organ failure. In the initial disease phase,
      the therapeutic measures are focused on (aggressive) volume replacement, early
      enteral nutrition and adequate analgesia. Characteristic in the course of severe
      acute pancreatitis are abdominal necroses, which require individualized and
      interdisciplinary treatment with antibiotic therapy, drainage and definitive
      necrosectomy. Necrosectomy should be planned as a "step-up approach" using
      interventional-radiological, endoscopic and minimally invasive surgical
      procedures.

PMID- 30094502
TI  - [Interactions between lung and kidney in the critically ill].
AB  - Interactions between lung and kidney can significantly affect the course of acute
      diseases, a phenomenon that was first observed in the 1950s by describing
      pulmonary dysfunction in uremic patients. From animal experiments there is ample
      evidence for remote lung injury following acute kidney injury (AKI), with an
      increased risk for the development of pulmonary edema and acute respiratory
      distress syndrome (ARDS). Coincident ARDS and AKI are associated with higher
      rates of intubation and mechanical ventilation, significantly prolonged weaning
      from mechanical ventilation and increased mortality. On the other hand, acute
      lung diseases and mechanical ventilation can promote the development of AKI and
      are associated with increased mortality when AKI is also present. These
      bidirectional interactions may include hemodynamic adverse effects during
      mechanical ventilation or volume overload as well as the release or decreased
      clearance and metabolism of proinflammatory mediators (e.g., interleukin-6 and
      tumor necrosis factor-alpha), which may induce and aggravate distant organ
      injury. The aim of this work is to examine the interactions between lung and the
      kidney in critically ill patients, as well as discuss potential preventive
      approaches.

PMID- 30094504
TI  - Transverse microvibrations-based guide wires drag reduction evaluation for
      endovascular interventional application.
AB  - When conducting endovascular interventional surgery, doctors usually experience
      high viscous resistance resulting from direct contact with blood when operating
      the guide wire in blood vessels, which reduces the operational efficiency.
      Improper operation can cause vascular injuries and greatly reduce surgical
      safety, sometimes leading to the death of the patient. This paper presents a new
      method that applies transverse microvibrations at the proximal end of a
      conventional passive guide wire to reduce viscous resistance. The effect of the
      proposed method in reducing the viscous resistance in the fluid is studied. The
      influences of the tube diameter, medium density, and applied vibration frequency
      on the viscous force are investigated. Finally, for endovascular therapy, a
      mathematical model of the viscous force of the guide wire based on the proposed
      method is established in the environment of human blood vessels to predict the
      magnitude of the viscous force exerted on the guide wire and analyze the drag
      reduction effect of the proposed method. The effectiveness of the proposed method
      in drag reduction and its feasibility in improving surgical safety are
      experimentally demonstrated. The experimental results indicate that the proposed
      method can assist the doctor during complicated and variable operation
      conditions.

PMID- 30094505
TI  - A combined approach for the development of novel sutures with antibacterial and
      regenerative properties: the role of silver and silk sericin functionalization.
AB  - Chronic wounds and related infections cause physical and psychological distress
      in patients, increased mortality, disability and high health care costs. The
      healing process can be delayed by several factors and in particular by the risk
      of infections, which can be further complicated by the increasing number of
      antibiotic-resistant microorganisms. New approaches in wounds management have
      been encouraged, aiming at preventing infections and improving wound healing. In
      this scenario, silver has emerged as an ideal antimicrobial agent due to its
      recognized efficacy against bacteria, viruses and fungi. Moreover, silk and in
      particular silk sericin from Bombyx mori has demonstrated excellent biological
      properties and can be considered a good candidate for skin tissue engineering. In
      this study absorbable PLGA sutures were functionalized with silk sericin and,
      then, they were treated with silver through an in situ photochemical deposition
      technology in order to develop an antibacterial and regenerative biomedical
      device. Morphological analysis was performed by Scanning Electron Microscopy and
      Energy Dispersive X-Ray Spectroscopy (SEM-EDX) in order to evaluate the presence
      and distribution of silver deposited on the sutures. The stability and durability
      of the sericin/silver coatings were tested and the results were related to both
      antibacterial properties and sample degradation. The biological analyses also
      aimed at studying the biocompatibility and wound healing properties of the
      device, evaluating the synergistic effect between sericin and silver.

PMID- 30094506
TI  - Body and organ metabolic rates of a cave fish, Triplophysa rosa: influence of
      light and ontogenetic variation.
AB  - Triplophysa rosa is a typical species of cave-dwelling fish distributed
      throughout Wulong County, Chongqing, China. This study aimed to test whether T.
      rosa has a low metabolic level as a cave species and how the metabolic rate of
      this fish responds to light stimulation. The whole body and organ (including
      brain, heart, and liver) oxygen consumption rates ([Formula: see text]) and
      several blood parameters related to oxygen carrying were compared between T. rosa
      acclimated in constant dark and those in regular photoperiod conditions. No
      significant changes in any variables were observed between the regular
      photoperiod fish and the dark fish, suggesting that the metabolic consumption of
      T. rosa is not light sensitive, which may be attributed to the highly degraded
      eyes of this cave species. The average mass-specific resting [Formula: see text]
      of T. rosa was 38.3 mgO2 kg- 1 h- 1 and was lower than many other fish species.
      One possible explanation for the low metabolic level of T. rosa can be due to its
      highly degraded eyes and small brain size. Whole-organ [Formula: see text] of the
      brain, heart, and liver were on average responsible for 8.18%, 3.55%, and 8.61%
      of the body resting [Formula: see text], respectively. Both heart mass and liver
      mass increased with increasing body mass; however, brain mass did not correlate
      with body mass. Maintaining a small brain size throughout ontogeny suggests
      energy-saving advantages for this cave species.

PMID- 30094508
TI  - Identification of reference genes suitable for RT-qPCR studies of murine
      gastrulation and patterning.
AB  - Quantitative reverse transcriptase PCR (RT-qPCR), a powerful and efficient means
      of rapidly comparing gene expression between experimental conditions, is
      routinely used as a phenotyping tool in developmental biology. The accurate
      comparison of gene expression across multiple embryonic stages requires
      normalisation to reference genes that have stable expression across the time
      points to be examined. As the embryo and its constituent tissues undergo rapid
      growth and differentiation during development, reference genes known to be stable
      across some time points cannot be assumed to be stable across all developmental
      stages. The immediate post-implantation events of gastrulation and patterning are
      characterised by a rapid expansion in cell number and increasing specialisation
      of cells. The optimal reference genes for comparative gene expression studies at
      these specific stages have not been experimentally identified. In this study, the
      expression of five commonly used reference genes (H2afz, Ubc, Actb, Tbp and
      Gapdh) was measured across murine gastrulation and patterning (6.5-9.5 dpc) and
      analysed with the normalisation tools geNorm, Bestkeeper and Normfinder. The
      results, validated by RT-qPCR analysis of two genes with well-documented
      expression patterns across these stages, indicated the best strategy for RT-qPCR
      studies spanning murine gastrulation and patterning utilises the concurrent
      reference genes H2afz and Ubc.

PMID- 30094509
TI  - PEG10 counteracts signaling pathways of TGF-beta and BMP to regulate growth,
      motility and invasion of SW1353 chondrosarcoma cells.
AB  - Recently, we reported highly active transforming growth factor (TGF)-beta and
      bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and
      concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10
      expression was suppressed by TGF-beta signaling, and PEG10 interfered with the
      TGF-beta and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of
      PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report
      that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-beta1
      mediated suppression. In contrast, PEG10 knockdown augments the TGF-beta1-induced
      motility of SW1353 cells. Individually, TGF-beta1 and PEG10 siRNA increase AKT
      phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10
      silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which
      was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by
      inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, 
      3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further
      upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced
      phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and
      MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206
      impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of
      MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating
      cell growth by suppressing TGF-beta signaling and inhibiting cell motility and
      invasion by interfering with TGF-beta and BMP signaling via the AKT and p38
      pathways, respectively. Thus, PEG10 might be a molecular target for suppressing
      the aggressive phenotypes of chondrosarcoma cells.

PMID- 30094510
TI  - Heart Transplantation and Mechanical Circulatory Support in Adults with
      Congenital Heart Disease.
AB  - PURPOSE OF REVIEW: To assess current management strategies for advanced heart
      failure in adults with congenital heart disease, including heart transplantation
      and mechanical circulatory support. RECENT FINDINGS: Current data demonstrate
      that adults with CHD generally experience higher short-term mortality after heart
      transplantation and MCS implantation, but enjoy superior long-term survival. Such
      patients are nonetheless less likely to receive a transplant than non-ACHD peers
      due to a variety of factors, including lack of applicability of current listing
      criteria to HF in ACHD. MCS is underutilized in ACHD, but provides similar
      quality of life benefits for ACHD and non-ACHD patients alike. Heart failure in
      ACHD is complex and difficult to treat, and both heart transplantation and
      mechanical circulatory support are often challenging to implement in this patient
      population. However, long-term results are encouraging, and existing data
      supports increasing use of MCS and transplant earlier in their disease course.
      Multidisciplinary care is critical to success in these complex patients.

PMID- 30094511
TI  - Radiation therapy in indolent primary cutaneous B cell lymphoma: a single
      institute experience.
AB  - To report the clinical results after definitive radiotherapy (RT) for indolent
      primary cutaneous B cell lymphoma (pcBCL). The data concerning all patients
      treated for indolent pcBCL with RT with a curative intent between 1992 and 2012
      were reviewed. All cases were (re)classified according to the World Health
      Organization (WHO) guidelines. A total of 42 patients with biopsy-proven primary
      cutaneous follicle center lymphoma (pcFCL) and primary cutaneous marginal zone
      lymphoma (pcMZL) were included. The median follow-up is 9.5 years. Treatment with
      RT resulted in complete response (CR) in all patients. Eight patients showed one
      or multiple relapses confined to the skin. No in-field recurrences were observed.
      For the entire cohort, the 10-year relapse-free survival (RFS) and overall
      survival (OS) were 71.1% and 87.1%, respectively. Univariate (UA) and
      multivariate (MA) analysis revealed extra-trunk primary lesion (MA) and multiple
      lesions (UA) as unfavorable prognostic factors. The 5-year RFS rate for patients
      with trunk lesion was 89.4% versus 66.9% for those with other location (p =
      0.02). The 5-year RFS rates were 83.5 and 57.1% in case of single and multiple
      lesions (p = 0.04). An excellent survival can be achieved with definitive RT in
      indolent pcBCL. Patients with multiple and extra-trunk primary cutaneous lesions
      probably warrants intensification of therapy. Prospective studies are mandatory.

PMID- 30094507
TI  - Human hyper-IgE syndrome: singular or plural?
AB  - Spectacular progress has been made in the characterization of human hyper-IgE
      syndrome (HIES) over the last 50 years. HIES is a primary immunodeficiency
      defined as an association of atopy in a context of very high serum IgE levels,
      characteristic bacterial and fungal diseases, low-level clinical and biological
      inflammation, and various non-hematopoietic developmental manifestations.
      Somewhat arbitrarily, three disorders were successively put forward as the
      underlying cause of HIES: autosomal dominant (AD) STAT3 deficiency, the only
      disorder corresponding to the original definition of HIES, and autosomal
      recessive (AR) DOCK8 and PGM3 deficiencies, in which atopy and high serum IgE
      levels occur in a context of manifestations not seen in patients with typical
      HIES. Indeed, these three disorders disrupt different molecular pathways, affect
      different cell types, and underlie different clinical phenotypes. Surprisingly,
      several other inherited inborn errors of immunity in which serum IgE levels are
      high, sometimes almost as high as those in HIES patients, are not considered to
      belong to the HIES group of diseases. Studies of HIES have been further
      complicated by the lack of a high serum IgE phenotype in all mouse models of the
      disease other than two Stat3 mutant strains. The study of infections in mutant
      mice has helped elucidate only some forms of HIES and infection. Mouse models of
      these conditions have also been used to study non-hematopoietic phenotypes for
      STAT3 deficiency, tissue-specific immunity for DOCK8 deficiency, and cell lineage
      maturation for PGM3 deficiency. We review here the history of the field of HIES
      since the first clinical description of this condition in 1966, together with the
      three disorders commonly referred to as HIES, focusing, in particular, on their
      mouse models. We propose the restriction of the term "HIES" to patients with an
      AD STAT3-deficiency phenotype, including the most recently described AR ZNF341
      deficiency, thus excluding AR DOCK8 and PGM3 deficiencies from the definition of
      this disease.

PMID- 30094513
TI  - Complete genome sequence of a novel virus, classifiable within the Potyviridae
      family, which infects passion fruit (Passiflora edulis).
AB  - We report the complete nucleotide sequence of a new member of the Potyviridae
      family isolated from passion fruit plants grown in Israel, called Passiflora
      edulis symptomless virus (PeSV). The PeSV genome is 9,928 nucleotides long and
      encodes a 3,173 amino acids polyprotein that is predicted to be proteolytically
      cleaved into 10 mature peptides. Our phylogenetic analysis shows that PeSV
      represents a new species, and is most closely related to rose yellow mosaic virus
      (RoYMV). According to currently accepted criteria for genus demarcation, both
      viruses should be assigned as representative isolates of new species in the
      recently approved genus, Roymovirus, in the Potyviridae family.

PMID- 30094512
TI  - Adaptation and tolerance mechanisms developed by mycorrhizal Bipinnula fimbriata
      plantlets (Orchidaceae) in a heavy metal-polluted ecosystem.
AB  - The adaptation and performance of orchid mycorrhizae in heavy metal-polluted
      soils have been poorly explored. In the present study, proteomic and metabolic
      approaches were used to detect physiological changes in orchid roots established
      in a heavy metal-polluted soil and to ascertain whether mycorrhizal fungi affect
      the metabolic responses of roots. Young Bipinnula fimbriata plantlets were
      established in control and heavy metal-polluted soils in a greenhouse. After 14
      months, exudation of root organic acids, phenolics, percentage of mycorrhization,
      mineral content, and differential protein accumulation were measured. More root
      biomass, higher root colonization, and higher exudation rates of citrate,
      succinate, and malate were detected in roots growing in heavy metal-polluted
      soils. Higher accumulation of phosphorus and heavy metals was found inside
      mycorrhizal roots under metal stress. Under non-contaminated conditions, non
      mycorrhizal root segments showed enhanced accumulation of proteins related to
      carbon metabolism and stress, whereas mycorrhizal root segments stimulated
      protein synthesis related to pathogen control, cytoskeleton modification, and
      sucrose metabolism. Under heavy metal stress, the proteome profile of non
      mycorrhizal root segments indicates a lower induction of defense mechanisms,
      which, together with the stimulation of enzymes related to carotenoid
      biosynthesis and cell wall organization, may positively influence mycorrhizal
      fungi colonization. The results point to different metabolic strategies in
      mycorrhizal and non-mycorrhizal root segments that are exposed to heavy metal
      stress. The results indicate that root colonization by mycorrhizal fungi is
      stimulated to alleviate the negative effects of heavy metals in the orchids.

PMID- 30094514
TI  - Complete genome analysis of bacteriophage AsXd-1, a new member of the genus
      Hk97virus, family Siphoviridae.
AB  - AsXd-1, a bacteriophage that infects Aeromonas salmonicida, was isolated from the
      wastewater of a seafood market in Shenzhen, China. The 39,014-bp genome of this
      phage contains 52 open reading frames (ORFs), 30 of which were found to be
      homologous to reference sequences that putatively encode functional phage
      proteins. Nine out of the remaining 22 ORFs with unknown functions were unique to
      AsXd-1. Gene annotation suggests that AsXd-1 has both lysogenic and lytic life
      cycles. Furthermore, both phylogenetic analysis based on the large subunit of
      terminase and genome sequence comparisons show that AsXd-1 is closely related to
      phages belonging to the genus Hk97virus. We thus propose AsXd-1 as a new member
      of the genus Hk97virus within the family Siphoviridae.

PMID- 30094515
TI  - Approaches to Eliminate Radiation Exposure in the Management of Pediatric
      Urolithiasis.
AB  - PURPOSE OF REVIEW: Traditional management of pediatric urolithiasis has been
      associated with a significant amount of radiation exposure. The steady increase
      in pediatric urolithiasis in recent years has raised concerns of long-term
      consequences in this special population. This review seeks to highlight the newer
      insights towards eliminating radiation exposure in pediatric urolithiasis from
      contemporary literature. RECENT FINDINGS: Establishing a clinical care pathway
      restricting usage of computed tomography in emergency rooms in suspected
      pediatric urolithiasis can eliminate unnecessary radiation exposure. Ultrasound
      can successfully replace fluoroscopy at ureteroscopy and percutaneous
      nephrolithotomy. Accredited technicians who use optimized settings combined with
      dose monitoring can significantly reduce fluoroscopic radiation. Radiation
      exposure in pediatric urolithiasis can be significantly reduced and potentially
      eliminated by employing standard protocols during workup, intervention, and
      follow-ups. Larger studies can support the feasibility of routinely performing
      ultrasound-guided surgeries instead of fluoroscopy. There is a need for
      development of consensus towards standardization of the management of pediatric
      urolithiasis.

PMID- 30094516
TI  - Disgust in Anxiety and Obsessive-Compulsive Disorders: Recent Findings and Future
      Directions.
AB  - PURPOSE OF REVIEW: In the past 20 years, the role of disgust in anxiety disorders
      and obsessive-compulsive disorder (OCD) has been investigated with increasing
      precision. In this review, we examine recent evidence implicating disgust in
      anxiety and OCD, highlighting recent measurement and methodological improvements.
      Specific emphasis is placed on understanding the mechanisms that may account for
      the role of disgust in OCD and related disorders. RECENT FINDINGS: Recent
      developments include clarification of the role of distinct disgust-relevant
      vulnerabilities in the etiology of anxiety and OCD, an improved understanding of
      the neurobiology of disgust processing in OCD, and an increased focus on disgust
      related mechanisms that contribute to psychopathology, such as disgust-based
      learning and emotion regulation. Disgust proneness is increasingly linked with
      symptoms of anxiety and OCD. However, further examination of the mechanisms that
      account for the roles of distinct disgust-relevant vulnerabilities is needed, and
      studies that directly examine disgust during the course of treatment are limited.
      Increasingly, the field has moved toward experimental investigation of specific
      disgust-relevant mechanisms that influence the etiology and treatment of OCD and
      related anxiety disorders.

PMID- 30094517
TI  - Intracortical facilitation within the migraine motor cortex depends on the
      stimulation intensity. A paired-pulse TMS study.
AB  - INTRODUCTION: Connectivity within the primary motor cortex can be measured using
      the paired-pulse transcranial magnetic stimulation (TMS) paradigm. This evaluates
      the effect of a first conditioning stimulus on the motor evoked potential (MEP)
      elicited by a second test stimulus when different interstimulus intervals are
      used. Aim of the present study was to provide, in patients suffering from
      migraine without aura (MwoA), additional information on intracortical
      facilitation (ICF), short intracortical inhibition (SICI), and long intracortical
      inhibition (LICI), using different intensities of the test stimulus (TS).
      METHODS: We enrolled 24 patients with episodic MwoA and 24 age- and sex-matched
      healthy volunteers. Both patients and controls were randomly assigned to two
      different experimental groups: the first group underwent evaluation of ICF, while
      in the second group we assessed SICI and LICI. All these measures were assessed
      by using three different suprathreshold intensities of the TS (110%, 130% and
      150% of the resting motor threshold, RMT). Interstimulus intervals (ISIs) of 10
      ms were used for testing ICF, while SICI and LICI were carried out by using 2 ms
      and 100 ms ISIs respectively. All migraine patients underwent the experimental
      protocol while in the interictal pain-free state. RESULTS: A main finding of the
      study was that an increased ICF could be seen in migraineurs as compared to the
      healthy subjects only by using a 110% intensity of the TS. Instead, no
      significant differences were observed between patients and controls as regards
      both measures of intracortical inhibition. CONCLUSION: We show that
      hyperresponsivity of the glutamatergic intracortical circuits can be detected in
      the migraine motor cortex only by applying a low suprathreshold intensity of
      stimulation. Our results strengthen the notion that, to be reliable, the
      assessment of cortical excitability in migraine should always include evaluation
      of the cortical response to different stimulation intensities.

PMID- 30094519
TI  - Be True to Our Schools-Models of Care in College Mental Health.
AB  - PURPOSE OF REVIEW: To review and synthesize the previous, current, and proposed
      models of care in college mental health in order to identify best practices that
      will address the mental health needs of today's students. To highlight data that
      supports existing or proposed models and describe areas where more data is
      needed. RECENT FINDINGS: Despite the potentially appealing attributes of
      integrated care, empirical evidence supporting these systems and structures in
      campus settings is mixed. Recent surveys show less than half of campuses have an
      integrated mental health care model. Overall, there is only partial consensus on
      optimal models of campus mental health care. Mental health needs in college
      student populations are greater and more complex than ever. While the resources
      available are vast and varied, there is limited evidence to support which models
      and programs can best meet students' needs.

PMID- 30094518
TI  - Which Comes First? An Examination of Associations and Shared Risk Factors for
      Eating Disorders and Suicidality.
AB  - PURPOSE OF REVIEW: This narrative review evaluates recent literature on the
      associations between eating disorders and suicidality and discusses potential
      shared mechanisms that may account for these relationships. Additionally, the
      review highlights shortcomings with the literature to date and suggests avenues
      for future research. RECENT FINDINGS: Individuals with anorexia nervosa, bulimia
      nervosa, and binge eating disorder experience elevated rates of suicidality
      compared to the general population. Suicide risk is higher when eating disorders
      occur with other psychological conditions. Additionally, genetic factors, emotion
      dysregulation, trauma, stressful life events, and lack of body regard may have
      roles in the development of both eating disorders and suicidality. Much of the
      risk for suicidality in eating disorders appears to be driven by comorbid
      psychopathology and genetic factors. However, the lack of longitudinal research
      makes it difficult to draw conclusions about the directionality or temporality of
      these relations; thus, novel methods are needed.

PMID- 30094520
TI  - Neuroactive Steroids and Perinatal Depression: a Review of Recent Literature.
AB  - PURPOSE OF REVIEW: The purpose of this review is to provide a theoretical
      explanation and a review of the recent literature concerning the role of
      neuroactive steroids in perinatal depression, and to use this information to
      suggest future directions of research. RECENT FINDINGS: The bulk of the evidence
      on neuroactive steroids in perinatal depression concerns allopregnanolone. Recent
      studies have been mixed, with some studies finding a direct correlation between
      lower levels of allopregnanolone and increased depressive symptoms but other
      studies finding no relationship. Evidence concerning other neuroactive steroids
      and perinatal depression is sparse. Additional research is needed with larger
      sample sizes and better characterization across the perinatal period (rather than
      cross-sectionally). Because some studies point to a lag between neuroactive
      steroid dysregulation and subsequent symptoms, future research should consider
      interactions with other aspects of neuroactive steroid physiology, such as
      synthetic enzymes or receptor plasticity.

PMID- 30094521
TI  - Strain variation and antigenic divergence among Bordetella pertussis circulating
      strains isolated from patients in Iran.
AB  - Despite global efforts and widespread vaccination to control whooping cough
      (pertussis) caused by B. pertussis, the re-emergence of pertussis still is being
      reported all over the world. Antigenic divergence in B. pertussis virulence
      factors is one of the reasons of pertussis resurgence, resulting in dissimilarity
      of local and vaccine strains. In this study, clonal spread and variation of B.
      pertussis virulence factor in isolated strains from Iranian patients have been
      analyzed. A total of 100 B. pertussis isolates were obtained from Pertussis
      Reference Laboratory of Pasteur Institute of Iran. Real-time PCR were performed
      to confirm the B. pertussis strains. The genomic patterns of B. pertussis strains
      were analyzed by pulsed-field gel electrophoresis (PFGE). Predominant alleles of
      local strains were ptxP3, ptxA1, prn2, fim 2-1, fim3-2, and cya2. PFGE results
      showed 25 patterns clustered into 18 PFGE groups. A few similarities between the
      circulating isolates, vaccine, and standard strains were obtained. Significantly,
      48% of the isolates showed dominant pattern with different allelic profiles from
      vaccine strains. According to the genomic profiles, the clonal spread was
      observed among the circulating strains. Predominant virulence factor profile was
      also comparable with other countries. It may be suggested that strain variation
      between vaccine and local strains may have an effect on pertussis resurgence in
      Iran like other parts of the world.

PMID- 30094523
TI  - Concomitant transient global amnesia and takotsubo cardiomyopathy following a
      stressful event.

PMID- 30094522
TI  - Multicenter performance evaluation of the Unyvero IAI cartridge for detection of
      intra-abdominal infections.
AB  - Intra-abdominal infections (IAIs) are one of the most common type of infections
      in patients with sepsis and an important cause of death in intensive care units.
      Early detection and treatment are necessary to reduce patient complications and
      improve outcomes. The Unyvero IAI Application (Curetis GmbH) is the first
      automated assay to rapidly and simultaneously identify a large panel of bacteria,
      fungi, toxins, and antibiotic resistance markers directly from IAI-related
      samples. The assay was evaluated in four European clinical laboratories in
      comparison to routine microbiological practices. A total of 300 clinical samples
      were tested with an overall sensitivity of 89.3% and specificity of 99.5%, while
      time to results was reduced by an average of about 17 h compared to
      identification (ID) results and 41 h compared to full antibiotic susceptibility
      testing (AST) results. The Unyvero IAI was able to detect additional
      microorganisms compared with culture, in particular anaerobes, with most
      detections confirmed by sequencing. The most frequent resistance markers detected
      were mecA/mecC (n = 25), aacA4 (n = 20), and blaCTX-M (n = 17) and carbapenemase
      genes were identified in nine specimens. Further studies are now required to
      determine the clinical impact of this new rapid test which could play a role in
      the successful treatment of IAI.

PMID- 30094524
TI  - Using Clinical PK/PD Studies to Support No Clinically Meaningful Differences
      Between a Proposed Biosimilar and the Reference Product.

PMID- 30094525
TI  - WWOX-associated encephalopathies: identification of the phenotypic spectrum and
      the resulting genotype-phenotype correlation.
AB  - Epileptic encephalopathies are a group of disorders in which epileptiform
      abnormalities cause progressive deterioration in cerebral function. Genetic
      causes have been described in several of the epileptic encephalopathies, and many
      previously unknown genes have been identified. WW domain-containing
      oxidoreductase (WWOX) has recently been implicated in autosomal recessive
      spinocerebellar ataxia type 12 (SCAR12) and severe early-onset epileptic
      encephalopathy. With whole-exome sequencing, we identified a homozygous WWOX
      missense mutation, p.Leu239Arg, in a girl from a consanguineous family with
      psychomotor developmental delay, acquired microcephaly, and epileptic seizures.
      WWOX-related epileptic encephalopathy is a rare condition but it should be
      considered in cases having early epileptic spasms and parental consanguinity.

PMID- 30094526
TI  - Diastolic heart dysfunction is correlated with CTG repeat length in myotonic
      dystrophy type 1.
AB  - The aims of this study were to investigate the correlations of tri-nucleotide
      (CTG) repeat length with detailed echocardiography (ECHO) parameters that
      represent myocardial function and to find a relationship between heart function
      and CTG repeat length in adult-onset myotonic dystrophy type 1 (DM1). In this
      study, clinical data for patients with DM1, including age, onset age, CTG repeat
      length, Medical Research Council sum score (MRCSS), and 6-min walking test
      (6MWT), were recorded. In addition, ECHO parameters and cardiac conduction
      abnormalities were evaluated. Among the cardiac parameters, the EA ratio and left
      ventricular end-diastolic dimension (LVEDD) were significantly correlated with
      the CTG repeat length (p < 0.05). Interventricular septal thickness at end
      diastole was also significantly correlated with the 6MWT in a multivariate linear
      regression model (p < 0.05). In conclusion, motor function (MRCSS and 6MWT) and
      CTG repeat length significantly correlated with LV diastolic dysfunction in
      patients with DM1. More emphasis should be given to diastolic dysfunction, which
      is currently under-recognized, when evaluating patients with DM1 with no
      abnormalities in routine electrocardiography studies. Lastly, well-designed and
      longitudinal studies are warranted to characterize and understand the
      pathophysiology of diastolic dysfunction in DM1.

PMID- 30094527
TI  - Moyamoya complicated by thrombotic cerebrovascular accident in a Caucasian woman
      with collagenous colitis.

PMID- 30094528
TI  - A case of recurrent transient ischemic attacks: carotid stump syndrome or
      posterior cerebral artery syndrome?

PMID- 30094530
TI  - Elevating mothers' voices: recommendations for improved patient-centered
      postpartum.
AB  - The weeks and months after birth are vital not only for infant health but also
      for the health and well-being of women and families as a whole. The first 12
      weeks postpartum, also known as the 4th trimester, is part of a continuum of
      pregnancy to recovery and family adjustment. In the United States, this
      transitional period has been a neglected area for women's health, especially
      considering the inherent biological, physical, and social changes experienced by
      millions of women each year. The Patient-Centered Outcomes Research Institute
      supported the 4th Trimester Project to partner with new mothers, health care
      providers, and health advocates to better describe and understand unmet maternal
      postpartum health needs. Through woman-centered engagement, the patient
      researcher-clinician-advocate team co-developed priority areas for research,
      policy, communication, and health care service delivery.

PMID- 30094529
TI  - Biopolymers: Applications in wound healing and skin tissue engineering.
AB  - Wound is a growing healthcare challenge affecting several million worldwide.
      Lifestyle disorders such as diabetes increases the risk of wound complications.
      Effective management of wound is often difficult due to the complexity in the
      healing process. Addition to the conventional wound care practices, the bioactive
      polymers are gaining increased importance in wound care. Biopolymers are
      naturally occurring biomolecules synthesized by microbes, plants and animals with
      highest degree of biocompatibility. The bioactive properties such as
      antimicrobial, immune-modulatory, cell proliferative and angiogenic of the
      polymers create a microenvironment favorable for the healing process. The
      versatile properties of the biopolymers such as cellulose, alginate, hyaluronic
      acid, collagen, chitosan etc have been exploited in the current wound care
      market. With the technological advances in material science, regenerative
      medicine, nanotechnology, and bioengineering; the functional and structural
      characteristics of biopolymers can be improved to suit the current wound care
      demands such as tissue repair, restoration of lost tissue integrity and scarless
      healing. In this review we highlight on the sources, mechanism of action and
      bioengineering approaches adapted for commercial exploitation.

PMID- 30094531
TI  - Physical Activity Patterns and Correlates of 9-Month-Old Chinese Infants in the
      Macau Population.
AB  - Objectives Many obesity-related chronic diseases originate from unhealthy
      childhood habits. The aim of this study was to describe 9-month-old infants'
      physical activity levels and patterns and to examine the correlates.
      Understanding these factors is necessary for improving the effectiveness of
      physical activity intervention programs for infants. Methods In total, 143 infant
      mother dyads from Macau, SAR China, participated in this study. Physical activity
      (PA) was assessed by using the Actigraph GT3X+ accelerometer and the demographic
      variables were collected by questionnaires. Results The most important findings
      were that: (1) infants had more screen time during weekdays (p = .044); (2)
      infants and mothers were least active at 8 a.m. (both weekdays and weekends) in
      the morning and most active at 7 p.m. (weekdays) and 8 p.m. (weekends) in the
      evening; (3) infants' PA levels significantly correlated with their mothers' PA
      intensities during the weekends (r = .192, p = .036), especially the mothers'
      lower intensities in the mornings and evenings; (4) maternal BMI predicted the PA
      levels of the 9-month-old infants' (R2 = .06, beta = 29.188, p = .009).
      Conclusions for Practice Physical activity promotion programs for infants should
      be time-specific starting from early infancy. This study was one of the first to
      examine 9-month-old infants' PA levels, patterns and correlates. The results may
      be helpful in improving the effectiveness of future healthy lifestyle
      intervention programs for infants in Macau and in the region in general.

PMID- 30094533
TI  - Hybrid receptor structure/ligand-based docking and activity prediction in ICM:
      development and evaluation in D3R Grand Challenge 3.
AB  - In context of D3R Grand Challenge 3 we have investigated several ligand activity
      prediction protocols that combined elements of a physics-based energy function
      (ICM VLS score) and the knowledge-based Atomic Property Field 3D QSAR approach.
      Activity prediction models utilized poses produced by ICM-Dock with ligand bias
      and 4D receptor conformational ensembles (LigBEnD). Hybrid APF/P (APF/Physics)
      models were superior to pure physics- or knowledge-based models in our
      preliminary tests using rigorous three-fold clustered cross-validation and later
      proved successful in the blind prediction for D3R GC3 sets, consistently
      performing well across four different targets. The results demonstrate that
      knowledge-based and physics-based inputs into the machine-learning activity model
      can be non-redundant and synergistic.

PMID- 30094534
TI  - Fragment of the aspartyl-tRNA synthetase applicable as a shared classification
      and phylogenetic marker in particular representatives of the order
      Lactobacillales.
AB  - The order Lactobacillales represents a morphologically, metabolically, and
      physiologically diverse group of bacteria. Lactic acid bacteria represent the
      core of this phylogenetic group. They are a part of epiphytic microflora,
      fermented dairy, meat, fruit and vegetable products, and the digestive tract of
      humans and animals. Despite the fact that these bacteria form a phenotypically
      and genotypically heterogeneous group, their phylogenetic relationship enables to
      propose a common genetic marker usable in classification, typing, and phylogeny.
      By creation of consensus sequence based on available genomic sequences of some
      representatives of order Lactobacillales, a specific primer-pair binding variable
      region of aspS gene (length of 615 nts) encoding the aspartyl-tRNA synthetase was
      designed. This gene has not yet been used in classification and phylogeny of the
      order Lactobacillales, although it meets the requirements of molecular markers
      (distribution and single copy in bacterial genomes, functional constancy and
      genetic stability, sequence variability among taxonomic units, irreplaceable role
      in proteosynthesis). Primers were applied on 54 type and wild Lactobacillales
      strains. Obtained sequences allowed to provide alignments for purpose of
      phylogenetic tree reconstructions that uncovered particular phylogenetic clusters
      of vagococci/enterococci, obligately homofermentative and heterofermentative
      lactobacilli. Although a relatively short fragment of the aspS gene
      (approximately 33% of the complete gene sequence) was evaluated, much higher
      sequence variability (61.8% of pairwise identity) among strains examined compared
      with 16S rRNA gene (90.7%, length of 1318 nt) provides a relatively simple and
      effective tool for classification and typing of selected representatives of the
      order Lactobacillales.

PMID- 30094532
TI  - Transcatheter aortic valve replacement in patients with severe aortic stenosis
      and heart failure.
AB  - Severe aortic stenosis (AS) and heart failure (HF) represent an important and
      high-risk group of patients who are often referred for transcatheter aortic valve
      replacement (TAVR) due to high risk for surgical intervention. Thus far,
      randomized controlled trials have shown comparable outcomes between TAVR and
      surgical aortic valve replacement in patients with severe AS and heart failure
      with reduced ejection fraction. In the current review, we will discuss (1) the
      pathophysiology of HF in patients with severe AS, (2) role of imaging modalities
      in management, (3) role of biomarkers of HF on prognosis, (4) impact of other
      valvular heart diseases, (5) evidence from the contemporary trials on the role of
      TAVR in patients with severe AS and HF, and (6) future directions and research.

PMID- 30094535
TI  - Clinical relevance of cytoskeleton associated proteins for ovarian cancer.
AB  - PURPOSE: Ovarian cancer has a high mortality rate and up to now no reliable
      molecular prognostic biomarkers have been established. During malignant
      progression, the cytoskeleton is strongly altered. Hence we analyzed if
      expression of certain cytoskeleton-associated proteins is correlated with
      clinical outcome of ovarian cancer patients. METHODS: First, in silico analysis
      was performed using the cancer genome atlas (TCGA), the human expression atlas
      and Pubmed. Selected candidates were validated on 270 ovarian cancer patients by
      qRT-PCR and/or by western blotting. RESULTS: In silico analysis revealed that
      mRNAs of 214 cytoskeleton-associated proteins are detectable in ovarian cancer
      tissue. Among these, we selected 17 proteins that participate in cancer disease
      progression and cytoskeleton modulation: KIF14, KIF20A, KIF18A, ASPM, CEP55,
      DLGAP5, MAP9, EB1, KATNA1, DIAPH1, ANLN, SCIN, CCDC88A, FSCN1, GSN, VASP and
      CDC42. The first ten candidates interact with microtubules (MTs) and the others
      bind to actin filaments. Validation on clinical samples of ovarian cancer
      patients revealed that the expression levels of DIAPH1, EB1, KATNA1, KIF14 and
      KIF18A significantly correlated with clinical and histological parameters of
      ovarian cancer. High DIAPH1, EB1, KATNA1 and KIF14 protein levels were associated
      with increased overall survival (OAS) of ovarian cancer patients, while high
      DIAPH1 and EB1 protein levels were also associated with low differentiation of
      respective tumors (G2/3). Moreover, DIAPH1 was the only protein, whose expression
      significantly correlated with increased recurrence-free interval (RFI).
      CONCLUSION: Mainly the expression levels of the MT-associated proteins analyzed
      in this study, correlated with prolonged survival of ovarian cancer patients.
      From > 200 genes initially considered, 17 cytoskeletal proteins are involved in
      cancer progression according to the literature. Among these, four proteins
      significantly correlated with improved survival of ovarian cancer patients.

PMID- 30094538
TI  - In vitro interaction between Plasmodium falciparum myosin B (PfMyoB) and myosin A
      tail interacting protein (MTIP).
AB  - Apicomplexan parasites, including Plasmodium falciparum, are obligate
      intracellular organisms that utilize a strategy termed "gliding" to move and
      invade host cells, causing disease. Gliding is carried out by a protein complex
      known as the glideosome, which includes an actin-myosin motor. To date, six
      myosins have been identified in P. falciparum (PfMyoA, B, C, D, E, and F), but
      only the role of PfMyoA, the myosin of the glideosome that is involved in the
      process of red blood cell and mosquito cell invasion, has been established. Based
      on previous observations, we speculated that PfMyoA and PfMyoB may have similar
      or redundant functions. To test this hypothesis, we searched for in vitro
      interactions between PfMyoB and MTIP (myosin A tail interacting protein), the
      myosin light chain of PfMyoA. A set of differentially tagged PfMyoA, PfMyoB, and
      MTIP recombinant proteins was employed to specifically and simultaneously detect
      each myosin in competition assays and inhibition assays using specific peptides.
      MTIP potentially acts as the light chain of PfMyoB.

PMID- 30094537
TI  - Locally advanced gastric cancer: total iodine uptake to predict the response of
      primary lesion to neoadjuvant chemotherapy.
AB  - PURPOSE: Pathologic response to neoadjuvant chemotherapy is a prognostic factor
      in many cancer types. However, the existing evaluative criteria are deficient. We
      sought to prospectively evaluate the total iodine uptake derived from dual-energy
      computed tomography (DECT) in predicting treatment efficacy and progression-free
      survival (PFS) time in gastric cancer after neoadjuvant chemotherapy. METHODS:
      From October 2012 to December 2015, 44 patients with locally advanced gastric
      cancer were examined with DECT 1 week before and three cycles after neoadjuvant
      chemotherapy. The percentage changes in tumor area (%DeltaS), diameter (%DeltaD),
      and density (%DeltaHU) were calculated to evaluate the WHO, RESCIST, and Choi
      criteria. The percentage changes in tumor volume (%DeltaV) and total iodine
      uptake of portal phase (%DeltaTIU-p) were also calculated to determine cut-off
      values by ROC curves. The correlation between the different criteria and
      histopathologic tumor regression grade (Becker score) or PFS were statistically
      analyzed. RESULTS: Forty-four patients were divided into responders and non
      responders according to 43.34% volume reduction (P = 0.002) and 63.87% (P =
      0.002) TIU-p reduction, respectively. The %DeltaTIU-p showed strong (r = 0.602, P
      = 0.000) and %DeltaV showed moderate (r = 0.416, P = 0.005), while the WHO (r =
      0.075, P = 0.627), RECIST (r = 0.270, P = 0.077) and Choi criteria (r = 0.238, P
      = 0.120) showed no correlation with the Becker score. The differences in PFS time
      between the responder and non-responder groups were significant according to
      %DeltaTIU-p and Choi criteria (P = 0.001 and P = 0.013, respectively).
      CONCLUSIONS: The TIU-p can help predict pathological regression in advanced
      gastric cancer patients after neoadjuvant chemotherapy. In addition, the
      %DeltaTIU-p could be one of the potentially valuable predictive parameters of the
      PFS time.

PMID- 30094539
TI  - The discovery of Varroa destructor on drone honey bees, Apis mellifera, at drone
      congregation areas.
AB  - Varroa is an external parasitic mite of honey bees and is a vector of multiple
      viruses that can severely weaken or cause the failure of western honey bee
      colonies if untreated. Effective Varroa control is dependent upon a thorough
      understanding of Varroa biology, including how Varroa move between host colonies.
      Here, we highlight that drone (male) honey bees may also play a role in Varroa
      dispersal. Drones were collected and the number of Varroa per 100 drones was
      calculated for each of five drone congregation areas (mating sites). This study
      is the first to confirm that drones present at drone congregation areas do carry
      Varroa. Further experimentation is needed to determine the extent to which drone
      mediated movement may play a role in Varroa life history and/or to develop
      practical management strategies to limit drone-mediated movement of Varroa
      between honey bee hives.

PMID- 30094540
TI  - Lyophilisation as a simple and safe method for long-term storage of free-living
      amoebae at ambient temperature.
AB  - Free-living amoebae (FLA) are protozoa ubiquitously found in nature. As some
      species or strains of these FLA are pathogenic for humans and animals, they
      represent objects of medical and parasitological research worldwide. Storage of
      valuable FLA strains in laboratories is often time- and energy-consuming and
      expensive. The shipment of such strains as frozen stocks is cumbersome and
      challenging in terms of cooling requirements as well as of transport regulations.
      To overcome these difficulties and challenges in maintenance and transport, we
      present a new method to generate lyophilised samples of non-cyst-forming FLA
      (Ripella (Vannella) spp.) and cyst-forming FLA (Acanthamoeba spp.) strains which
      guarantees a simple mechanism for long-term storage at ambient temperature, as
      well as easy handling and/or shipment. The survival rate of all FLA lyophilisates
      after short-term storage (2 months) was comparable to the survival rate of freeze
      cultures of the respective strains. Furthermore, the viability of Acanthamoeba
      spp. cysts after storage for 29 months was 20 to 40% following lyophilisation and
      rehydration, with strain variation.

PMID- 30094536
TI  - Melanoma treatment: from conventional to nanotechnology.
AB  - INTRODUCTION: Melanoma is the most serious form of skin cancer causing most of
      the skin cancer-related deaths. The incidence of melanoma has risen so
      dramatically over past few years that no other solid or blood malignancy comes
      close to it in terms of increased incidence. The main problem associated with the
      treatment of melanoma is low response rate to the existing treatment modalities,
      which in turn is due to the incomplete response by chemotherapeutic agents and
      inherent resistance of melanoma cells. MATERIALS AND METHODS: Conventional
      therapeutic strategies, as well as, recent literature on melanoma have been
      thoroughly studied. This review summarizes the base of anti-melanoma treatment
      with conventional chemotherapeutic drugs, followed by an account of recent
      studies which explored the potential of nanotechnology and newer strategies and
      agents in melanoma treatment. CONCLUSION: Although melanoma is curable if
      detected in its early localized form, metastatic melanoma continues to be a
      therapeutic challenge. Metastatic melanoma has a very poor prognosis and
      conventional therapies have not improved the outcomes of the treatment so far.
      For this reason, newer combinations of anti-melanoma drugs and newer strategies
      utilizing nanotechnology have been constantly explored.

PMID- 30094541
TI  - Contact lens-related polymicrobial keratitis: Acanthamoeba spp. genotype T4 and
      Candida albicans.
AB  - A 31-year-old female daily user of contact lenses sought medical attention,
      reporting blurred vision and irritation of the left eye. Slit-lamp examination
      revealed hyperemia and an irregular corneal epithelium surface, and empirical
      treatment was started. A corneal scrape was obtained and examined for the
      presence of fungi, bacteria, and Acanthamoeba spp. The results of the microbial
      culture revealed growth of Acanthamoeba spp. and Candida albicans. The
      Acanthamoeba isolate was characterized by cyst morphology as belonging to group
      II according to Pussard and Pons. Sequencing of the diagnostic fragment 3 (DF3)
      region located on the 18S ribosomal DNA identified the isolate as genotype T4.
      The patient was treated with chlorhexidine 0.02% and polyhexamethylene biguanide
      (PHMB) 0.02% drops for 5 months until the infection resolved. Lately, rare cases
      of polymicrobial keratitis associated with Acanthamoeba and Candida albicans have
      been reported. Cases of co-infection are more difficult to treat, since the
      specific treatment depends on precise identification of the agents involved.

PMID- 30094542
TI  - Use of radiation dose index monitoring software in a multicenter environment for
      CT dose optimization.

PMID- 30094543
TI  - The influence of semantic associations on sentence production in schizophrenia:
      an fMRI study.
AB  - One of the most prominent symptoms of schizophrenia is thought disorder, which
      manifests itself in language production difficulties. In patients with thought
      disorders the associations are loosened and sentence production is impaired. The
      determining behavioral and neural mechanisms of sentence production are still an
      important subject of recent research and have not yet been fully understood. The
      aim of the current study was to examine the influence of associative relations
      and distractor modalities on sentence production in healthy participants and
      participants with schizophrenia. Therefore, reaction times and neural activation
      of 12 healthy subjects and 13 subjects with schizophrenia were compared in an
      adapted picture word interference paradigm (PWI). No significant group
      differences were found, neither on the behavioral nor on the neural level. On the
      behavioral level, for the entire group incremental sentence processing was found,
      i.e. processing of the second noun only starts after the first noun was
      processed. At the neural level, activation was discovered in the bilateral
      caudate nuclei and the cerebellum. Those activations could be related to response
      enhancement and suppression as well as to the modulation of cognitive processes.

PMID- 30094544
TI  - Brain responses to pictures of children in men with pedophilic disorder: a
      functional magnetic resonance imaging study.
AB  - Structural and functional neuroimaging techniques have recently been used to
      investigate the mechanisms of sexual attraction to children, a hallmark of
      pedophilic disorder, and have reported many contradictory or non-replicated
      findings. Here, our purpose was to identify through functional magnetic resonance
      imaging the brain responses of 25 male outpatients with pedophilic disorder to
      visual stimuli depicting children (VSc) and to compare them with 24 male healthy
      controls matched on sexual orientation (to female or male adults), age, and
      handedness. No region was differentially activated across the two groups in
      response to VSc. However, as shown by a random-effects statistical analysis
      (cluster-level pFWE-corrected < 0.05), in patients with pedophilia, but not in
      controls, the presentation of VSc induced a bilateral activation in the lateral
      occipital and temporal cortices, in particular in the right inferior temporal
      gyrus, as well as an activation in the declive of the cerebellar vermis. In
      addition, in patients the level of bilateral activation in the above-mentioned
      regions was positively correlated with ratings of perceived sexual arousal
      elicited by VSc. These results implicate these regions as possible candidate
      areas mediating sexual arousal in patients with pedophilic disorder.

PMID- 30094546
TI  - Predictive value of primary tumor parameters using 18F-FDG PET/CT for occult
      lymph node metastasis in breast cancer with clinically negative axillary lymph
      node.
AB  - OBJECTIVE: This study aimed to demonstrate the clinical significance of total
      lesion glycolysis (TLG) of primary breast cancer using 18F-FDG PET/CT to predict
      axillary lymph node (ALN) metastasis in invasive ductal breast cancer (IDC) with
      a clinically negative axillary lymph node (cN-ALN). METHODS: 135 patients, newly
      diagnosed with IDC with CN-ALN between July 2016 and October 2017, were
      retrospectively enrolled. We estimated primary tumor PET/CT parameters including
      the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and
      TLG, as well as clinicopathologic findings. All patients received breast surgery
      followed by pathologic axillary lymph node examination. RESULTS: Of the 135
      patients, 31 (23.0%) were diagnosed with pathologically proven metastatic ALN. In
      univariate analysis, SUVmax, MTV, and TLG of the primary breast tumor were
      correlated with metastatic ALN along with tumor size, lymphovascular invasion,
      CD34, and D2-40. On multivariate analysis, TLG (> 5.74, p = 0.009) had
      independent significance for predicting ALN metastasis in IDC with cN-ALN.
      CONCLUSION: We demonstrated that TLG of primary tumors can be useful in
      predicting pathologic ALN metastasis in IDC patients with cN-ALN.

PMID- 30094545
TI  - Randomized phase III trial to evaluate radiopharmaceuticals and zoledronic acid
      in the palliation of osteoblastic metastases from lung, breast, and prostate
      cancer: report of the NRG Oncology RTOG 0517 trial.
AB  - BACKGROUND: Skeletal-related events (SREs), common sequelae of metastatic cancer,
      are reduced by bisphosphonates. In this study, it was postulated that
      radiopharmaceuticals, added to bisphosphonates, could further decrease the
      incidence of SREs. METHODS: NRG Oncology RTOG 0517 randomized patients with
      breast, lung, and prostate cancer and blastic bone metastases to either
      zoledronic acid (ZA) alone or ZA plus radiopharmaceuticals (Sr-89 or Sm-153). The
      primary endpoint was time to development of SREs. Secondary objectives included
      quality of life (QOL), pain control, overall survival (OS), and toxicity.
      RESULTS: 261 patients (median age 68; 62% male; 55% prostate, 35% breast, 10%
      lung) were accrued between July 2006 and February 2011. The study closed early
      due to a lower than expected rate of SREs. 52 (42%) patients in the ZA arm and 49
      (40%) in the radiopharmaceutical arm experienced an SRE. Median time free of SREs
      was 29.9 and 27.4 months, respectively (p = 0.84). Median OS in the ZA arm and
      radiopharmaceutical arms was 32.1 and 26.9 months, respectively (p = 0.37). Cox
      proportional hazards regression model showed that primary disease site (lung) and
      number of bone metastases (> 2) had a negative impact on OS (p < 0.0001, p =
      0.01, respectively). The addition of radiopharmaceuticals to ZA led to a
      significant reduction in pain at 1 month based on BPI worst score (p = 0.02). No
      other group differences were noted for QOL or toxicity. CONCLUSION: The addition
      of radiopharmaceuticals to bisphosphonates did not alter time to SREs or OS for
      patients with breast, lung, prostate cancers and blastic bone metastases,
      although it was associated with significant pain reduction at 1 month. CLINICAL
      TRIAL REGISTRY: This protocol (RTOG 0517) is registered with ClinicalTrials.gov
      (NCT00365105), and may be viewed online at
      http://www.clinicaltrials.gov/ct2/show/NCT00365105?term=RTOG+0517&rank=1 .

PMID- 30094549
TI  - Clinical Characteristics of Asymmetric Bilateral Gynecomastia: Suggestion of
      Desirable Surgical Method Based on a Single-Institution Experience.

PMID- 30094548
TI  - The metabolic fate of fenclozic acid in chimeric mice with a humanized liver.
AB  - The metabolic fate of the human hepatotoxin fenclozic acid ([2-(4-chlorophenyl)
      1,3-thiazol-4-yl]acetic acid) (Myalex) was studied in normal and bile-cannulated
      chimeric mice with a humanized liver, following oral administration of 10 mg/kg.
      This in vivo animal model was investigated to assess its utility to study "human"
      metabolism of fenclozic acid, and in particular to explore the formation of
      electrophilic reactive metabolites (RMs), potentially unique to humans.
      Metabolism was extensive, particularly involving the carboxylic acid-containing
      side chain. Metabolism resulted in the formation of a large number of metabolites
      and involved biotransformation via both oxidative and conjugative routes. The
      oxidative metabolites detected included a variety of hydroxylations as well as
      cysteinyl-, N-acetylcysteinyl-, and cysteinylglycine metabolites. The latter
      resulted from the formation of glutathione adducts/conjugates providing evidence
      for the production of RMs. The production of other classes of RMs included acyl
      glucuronides, and the biosynthesis of acyl carnitine, taurine, glutamine, and
      glycine conjugates via potentially reactive acyl-CoA intermediates was also
      demonstrated. A number of unique "human" metabolites, e.g., those providing
      evidence for side-chain extension, were detected in the plasma and excreta of the
      chimeric liver-humanized mice that were not previously characterised in, e.g.,
      the excreta of rat and C57BL/6 mice. The different pattern of metabolism seen in
      these chimeric mice with a humanized liver compared to the conventional rodents
      may offer clues to the factors that contributed to the drug-induced liver injury
      seen in humans.

PMID- 30094547
TI  - A silver renaissance in dentistry.
AB  - AIMS: Recently, there has been interest in biological approaches for caries
      management, with techniques such as interim therapeutic restorations and Hall
      technique crowns showing comparative effectiveness against conventional
      restorative methods. One of these approaches is the use of silver diamine
      fluoride (SDF) as a restorative option. In this invited review, the aim was to
      critically appraise the currently available literature with regards to the
      indication, technique and outcome of SDF. METHODS: A review of the literature on
      SDF with a focus on its use in the primary dentition was conducted. RESULTS:
      There has been a recent explosion in the literature regarding the use of SDF,
      from in vitro studies on the mechanism to clinical studies on the effectiveness
      and patient acceptance of the technique. A systematic review in 2016 concluded
      that SDF application resulted in caries arrest in 81% of active lesions in
      primary teeth over 30 months. Additionally, over 60% of parents reported being
      satisfied with the aesthetic outcome with most children finding the procedure to
      be acceptable, comfortable and relatively pain-free. CONCLUSIONS: Silver diamine
      fluoride is a safe and effective alternative technique to caries management in
      the paediatric population. Given the ongoing worldwide debate on cost
      effectiveness of biological approaches coupled with the increasing concerns and
      limited accessibility of treatment under general analgesia, SDF should form an
      important addition to every dentist's armamentarium.

PMID- 30094550
TI  - Breast Implant-Associated Anaplastic Large Cell Lymphoma: Immediate or Delayed
      Implant Replacement?
AB  - INTRODUCTION: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)
      is a rare and recently described type of peripheral T-cell lymphoma. Fewer than
      550 cases have been reported worldwide. Although BIA-ALCL is usually indolent,
      early diagnosis and treatment have been shown to improve outcome. CASE
      DESCRIPTION: This case report describes the management of a 50-year-old healthy
      Caucasian woman presenting with rapid painful enlargement of the left breast.
      Imaging revealed findings consistent with BIA-ALCL. This diagnosis was confirmed
      by fine needle aspiration cytology and subsequent pathological analysis.
      Bilateral removal of implants, complete left capsulectomy and immediate bilateral
      implant exchange were performed. CONCLUSION: No consensus currently exists
      regarding optimal time of implant exchange and management of the contralateral
      capsule. The immediate replacement with smooth implants was thoroughly discussed
      with the patient and endorsed by expert opinion, given complete removal of the
      disease. There was no sign of recurrence at 6 months. Close clinical and
      radiological visits are planned for the next years. LEVEL OF EVIDENCE V: This
      journal requires that authors assign a level of evidence to each article. For a
      full description of these Evidence-Based Medicine ratings, please refer to the
      Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PMID- 30094552
TI  - Racial disparities in chemotherapy administration for early-stage breast cancer:
      a systematic review and meta-analysis.
AB  - PURPOSE: We conducted a systematic review and meta-analysis to measure the extent
      to which race is associated with delayed initiation or receipt of inadequate
      chemotherapy among women with early-stage breast cancer. METHODS: We performed a
      systematic search of all articles published from January 1987 until June 2017
      within four databases: PubMed/Medline, EMBASE, CINAHL, and Cochrane CENTRAL.
      Eligible studies were US-based and examined the influence of race on chemotherapy
      delays, cessation, or dose reductions among women with stage I, II, or III breast
      cancer. Data were pooled using a random effects model. RESULTS: A total of twelve
      studies were included in the quantitative analysis. Blacks were significantly
      more likely than whites to have delays to initiation of adjuvant therapy of 90
      days or more (OR 1.41, 95% CI 1.06-1.87; X2 = 31.05, p < 0.00001; I2 = 90%).
      There was no significant association between race and chemotherapy dosing. Due to
      overlap between studies assessing the relationship between race and completion of
      chemotherapy, we conducted two separate analyses. Black patients were
      significantly more likely to discontinue chemotherapy, however, this was no
      longer statistically significant when larger numbers of patients with more
      advanced (stage III) breast cancer were included. CONCLUSIONS: These results
      suggest that black breast cancer patients experience clinically relevant delays
      in the initiation of adjuvant chemotherapy more often than white patients, which
      may in part explain the increased mortality observed among black patients.

PMID- 30094551
TI  - Letrozole concentration is associated with CYP2A6 variation but not with
      arthralgia in patients with breast cancer.
AB  - PURPOSE: The aromatase inhibitor (AI) letrozole is a first-line drug in the
      adjuvant treatment of breast cancer in postmenopausal women. Adherence to AI
      therapy, including letrozole, remains problematic due to the development of
      debilitating AI-induced arthralgia. Letrozole is metabolized in the liver by
      CYP2A6. It remains unknown if plasma letrozole levels or CYP2A6 genetic variation
      is associated with the development of arthralgia. METHODS: We enrolled 126 female
      breast cancer patients initiated on letrozole therapy and prospectively collected
      blood samples at baseline and two follow-up time points to determine letrozole
      plasma concentrations and CYP2A6 genotype. At each visit, participants completed
      two validated questionnaires to assess the severity of arthralgia symptoms.
      RESULTS: More than half (55%) of patients experienced a significant increase in
      their arthralgia symptoms after initiation of treatment. The clinical variables
      of body mass index (P = 0.0003) and age (P = 0.0430) were negatively and
      positively associated with plasma letrozole concentrations, respectively. CYP2A6
      genotype was significantly associated with letrozole levels (P < 0.0001), and
      increased plasma letrozole levels were observed in patients with CYP2A6 reduced
      function genotypes. Plasma levels of letrozole and CYP2A6 genotype were not
      significantly associated with a change in pain score from baseline. CONCLUSIONS:
      CYP2A6 genotype was a significant predictor of letrozole plasma levels, but was
      not associated with the development of arthralgia.

PMID- 30094553
TI  - A comparison of the imaging features of pleomorphic and classical invasive
      lobular carcinoma.
AB  - PURPOSE: Pleomorphic invasive lobular carcinoma (pILC) is a distinct
      morphological variant of ILC with a poorer prognosis than classical ILC (cILC).
      The aim of this study was to ascertain whether the conventional imaging
      appearances of the two entities differ. METHODS: A single-center retrospective
      review of conventional imaging was undertaken in 150 consecutive patients with
      histopathologically confirmed ILC (38 pILC; 112 cILC) between April 2010 and July
      2015. Mammographic and sonographic findings were evaluated using the BI-RADS
      lexicon by a radiologist blinded to pathology, and the findings in the two groups
      were compared. The degree of discrepancy between imaging and pathological sizing
      in the two groups was evaluated. RESULTS: Lesions were mammographically occult in
      11% of pILC and 14% of cILC (p = 0.56). On mammography, skin or trabecular
      thickening and microcalcification were commoner in pILC than cILC (13% vs. 1%, p
      < 0.01; 25% vs. 5%, p < 0.01). Architectural distortion was more frequent in cILC
      than pILC (26% vs. 9%, p = 0.01). On ultrasound, pILC more frequently exhibited
      mixed echogenicity (28% vs. 13%; p = 0.04), skin thickening, subcutaneous or
      parenchymal edema (8% vs. 0%; p = 0.02), echogenic surrounding fat (33% vs. 9%; p
      < 0.01), and posterior acoustic enhancement (10% vs. 1%; p = 0.02) than cILC.
      CILC was more frequently manifested as a focal area of altered echogenicity (24%
      vs. 8%; p = 0.04). Mean elastography stiffness was higher for pILC (174.8 vs.
      124.6 kPa; p = 0.02). Imaging-pathological size disparity was similar for both
      subtypes. CONCLUSION: There are differences in the imaging features between pILC
      and cILC which reflect the more aggressive nature of pILC.

PMID- 30094554
TI  - Recurrence of cardiac myxoma in the right atrium with Carney complex following
      resection of myxomas in both ventricles.
AB  - We describe a case of Carney complex (CNC), a rare hereditary condition, that
      resulted in the development of cardiac myxomas. We would like to emphasize that
      we detected the first myxomas in both ventricles, followed by the second myxoma
      in the right atrium, although cardiac myxomas often originate in the left atrium.
      We highlight the heightened risk of recurrence and emphasize the importance of
      performing regular ultrasonic cardiac echography to preclude such outcomes.

PMID- 30094556
TI  - Dissociated effect and Chemosensitive enhancement of tumor spheroids influenced
      by an electric field in a microdevice.
AB  - The use of electric field for cancer therapy has been proposed for a novel non
      invasive cancer therapeutic approach that provides better quality of life for
      patients. However, argument of the efficacy hampers the therapeutic development
      for various cancer diseases. More scientific evidences are necessary to be
      addressed by basic research. The current in vitro cell culture study reports the
      responses of tumor spheroids after the application of an alternating electric
      field. Human hepatocarchinoma cells suspended in soft hydrogel were cultured in a
      cell culture device embedded with stimulating electrodes. Tumor spheroids
      gradually formed and alternating electric field was then applied during the
      culture course. Investigation of cell viability and cell cycle were conducted to
      optimize the treatment conditions. The results showed that the electric potential
      of 1.0 Vpp and frequency of 130 kHz was the minimal effective conditions for
      inhibiting tumor spheroids. Importantly, dissociation of tumor spheroids was
      observed after the treatment. The effectiveness of chemotherapeutic agents was
      shown to be enhanced while the electric filed was simultaneously applied to the
      tumor spheroids. These results provided solid foundation for developing the
      effective therapeutic strategies.

PMID- 30094555
TI  - Altered intra- and inter-hemispheric functional dysconnectivity in schizophrenia.
AB  - Despite convergent evidence suggesting that schizophrenia is a disorder of brain
      dysconnectivity, it remains unclear whether intra- or inter-hemispheric deficits
      or their combination underlie the dysconnection. This study examined the source
      of the functional dysconnection in schizophrenia. Resting-state fMRI was
      performed in 66 patients with schizophrenia and 73 matched healthy controls.
      Functional brain networks were constructed for each participant and further
      partitioned into intra- and inter-hemispheric connections. We examined how
      schizophrenia altered the intra-hemispheric topological properties and the inter
      hemispheric nodal strength. Although several subcortical and cingulate regions
      exhibited hemispheric-independent aberrations of regional efficiency, the optimal
      small-world properties in the hemispheric networks and their lateralization were
      preserved in patients. A significant deficit in the inter-hemispheric
      connectivity was revealed in most of the hub regions, leading to an inter
      hemispheric hypo-connectivity pattern in patients. These abnormal intra- and
      inter-hemispheric network organizations were associated with the clinical
      features of schizophrenia. The patients in the present study received different
      medications. These findings provide new insights into the nature of
      dysconnectivity in schizophrenia, highlighting the dissociable processes between
      the preserved intra-hemispheric network topology and altered inter-hemispheric
      functional connectivity.

PMID- 30094557
TI  - Pharmacovigilance workflow in Europe and Italy and pharmacovigilance terminology.
AB  - The terminology used in pharmacovigilance can cause confusion, because there are
      similar terms that describe different phenomena (e.g. adverse reactions, adverse
      drug reactions, and side effects). Incorrect use of terminology can have negative
      effects on the reporting of adverse drug reactions and on the interpretation of
      these reports. To explain the most common terms used in pharmacovigilance, this
      article first describes the pharmacovigilance workflow process in the European
      Union and, as an example, in Italy. Then, the article reviews common
      pharmacovigilance terms.

PMID- 30094558
TI  - EU pharmacovigilance regulatory requirements of anticancer biosimilar monoclonal
      antibodies.
AB  - An increasing number of innovative oncology monoclonal antibodies (mAbs) have
      been introduced into the global market, and biosimilar versions have now also
      been approved in Europe. Being complex to develop and difficult to manufacture,
      the biosimilar is a drug similar but not identical in physicochemical
      characteristics, efficacy, and safety to an original biological drug already
      approved in the European Union, for which marketing exclusivity rights have
      expired. Generally, the safety monitoring of biosimilars follows the same
      requirements that apply to all biologicals, even if specific pharmacovigilance
      measures exist and some of them are still being debated. The manufacturing
      process, immunogenicity, traceability, and extrapolation of indication are
      keywords which may impact on the achievement of additional knowledge about the
      safety of a biosimilar mAb. In this article, we aim to discuss elements that play
      a central role in the pharmacovigilance legislation of biosimilar mAbs.

PMID- 30094559
TI  - Healthcare professionals' knowledge, attitude and practice towards adverse drug
      reaction (ADR) reporting at the health center level in Ethiopia.
AB  - Background Adverse drug reactions (ADRs) are major health problems which are of
      global concern. Spontaneous reporting of adverse drug reactions constitutes a
      crucial contribution to patient care. Objective The purpose of this study was to
      assess the knowledge, attitudes, and practices of healthcare professionals
      towards adverse drug reaction reporting. Setting Health care professionals in
      Gondar, Ethiopia. Methods A cross-sectional study was conducted from March to May
      2017. Data were collected through self-administered questionnaires. The collected
      data were analyzed using SPSS version 20. Binary logistic regression analysis was
      performed to distinguish factors that affect adverse drug reaction reporting. A p
      value < 0.05 was considered as a statistically significant. Main outcome measure
      Factors affecting adverse drug reaction reporting of health care professionals.
      Results Of 102 healthcare professionals included in this study, 61 (59. 8%) were
      nurses, 16 (15.7%) health officers, and 25 (24.5%) pharmacy professionals. Nearly
      48 (47%) study participants had an inadequate level of knowledge towards adverse
      drug reaction reporting. The majority of participants 88 (86.3%) had a positive
      attitude, while more than half (51%) of study participants did not report the
      adverse drug reaction they encountered. Participants who had not taken adverse
      drug reaction reporting training (p = 0.037), health officers (p = 0.019), and
      nurse professionals (p = 0.001) showed a statistically significant association
      with an inadequate level of knowledge. Conclusion Even though the majority of
      healthcare professionals had a positive attitude, they had an inadequate level of
      knowledge and practice towards adverse drug reaction reporting.

PMID- 30094560
TI  - Bone density correlates with clinical outcomes after ankle fracture fixation.
AB  - INTRODUCTION: Osteoporosis and decreased bone density are known to increase
      fracture incidence and severity. Although much is known regarding the effects of
      bone density on fracture risk and the treatment options for prevention of
      fragility fractures, whether bone quality alters clinical outcomes after fracture
      fixation is unknown. The purpose of this study was to determine whether bone
      quality correlates with clinical outcomes after fracture fixation. MATERIALS AND
      METHODS: A prospective database of all operatively treated ankle fractures by a
      single surgeon from 2003 to 2013 was used to identify patients. All patients
      included in the study had preoperative computed tomography (CT) imaging of the
      injured ankle and postoperative CT imaging of the contralateral ankle. Hounsfield
      unit (HU) measurement values were determined by placing an elliptical region of
      interest confined to the cancellous metaphyseal region of the distal tibia and
      fibula. The primary and secondary clinical outcomes included Foot and Ankle
      Outcome Scores (FAOS) and ankle range of motion (ROM). Included patients had at
      least 12 months of clinical outcome data. RESULTS: Sixty-four patients met the
      inclusion criteria. Comparison of HU values from the injured and contralateral
      side demonstrated almost perfect agreement (ICC(2,1) = 0.938), suggesting that HU
      values can be accurately measured in the setting of a fracture. Increased HU
      values of the injured distal tibia and fibula significantly correlated with
      improved outcomes in four of five FAOS domains, including pain, activities of
      daily living, sports, and quality of life (beta = 0.285-0.344; P <= 0.05 for
      all). Range of motion outcomes did not significantly correlate with HU values.
      CONCLUSIONS: Our results suggest that decreased bone quality, as measured using
      preoperative CT, significantly correlates with inferior short-term clinical
      outcomes. These results have significant implications for integrating bone
      quality into treatment algorithms for fracture patients.

PMID- 30094561
TI  - Validity and responsiveness of Barthel index for measuring functional recovery
      after hemiarthroplasty for femoral neck fracture.
AB  - INTRODUCTION: To investigate the validity of Barthel Index (BI) compared with de
      Morton Mobility Index (DEMMI), EuroQol-visual analog scale (EQ-VAS), 2-min walk
      test (2MWT), and timed get-up-and-go test (TUG), and to evaluate the
      responsiveness of all outcome measures for assessing functional recovery in older
      patients who underwent hemiarthroplasty after femoral neck fracture. MATERIAL AND
      METHOD: Eighty-one femoral neck fracture patients who were enrolled in a study
      evaluating functional recovery after bisphosphonate therapy during 2013 to 2015,
      and who had data available at both baseline and 12 months after surgery were
      included in this study. RESULTS: All scores improved significantly from baseline
      to the 1-year follow-up. BI had moderate to strong correlation with DEMMI, 2MWT,
      and TUG (r-value: 0.490-0.843), and mild to moderate correlation with EQ-VAS (r
      value: 0.278-0.323). All outcome measurements had high effect estimates. The
      minimal clinically important difference (MCID) of BI at 12 months was 9.8 points.
      CONCLUSION: Since BI was shown to have good validity (moderate to strong
      correlation with DEMMI and performance-based tests, and mild to moderate
      correlation with EQ-VAS), BI can be used to accurately assess functional recovery
      in patients who undergo hemiarthroplasty after femoral neck fracture.

PMID- 30094562
TI  - For whom is social-network usage associated with anxiety? The moderating role of
      neural working-memory filtering of Facebook information.
AB  - Is Facebook usage bad for mental health? Existing studies provide mixed results,
      and direct evidence for neural underlying moderators is lacking. We suggest that
      being able to filter social-network information from accessing working memory is
      essential to preserve limited cognitive resources to pursue relevant goals.
      Accordingly, among individuals with impaired neural social-network filtering
      ability, enhanced social-network usage would be associated with negative mental
      health. Specifically, participants performed a novel electrophysiological
      paradigm that isolates neural Facebook filtering ability. Participants' actual
      Facebook behavior and anxious symptomatology were assessed. Confirming evidence
      showed that enhanced Facebook usage was associated with anxious symptoms among
      individuals with impaired neural Facebook filtering ability. Although less robust
      and tentative, additional suggestive evidence indicated that this specific
      Facebook filtering impairment was not better explained by a general filtering
      deficit. These results involving a neural social-network filtering moderator, may
      help understand for whom increased online social-network usage is associated with
      negative mental health.

PMID- 30094564
TI  - Risk of cardiac tachyarrhythmia in patients with repaired tetralogy of Fallot: a
      multicenter cardiac MRI based study.
AB  - Cardiac tachyarrhythmias are the leading cause of morbidity and mortality in
      patients with repaired tetralogy of Fallot (TOF). We evaluated risk factors for
      sustained ventricular tachyarrhythmia (VT) and atrial tachyarrhythmia (ATA) in
      these patients. Patients (n = 319) who underwent cardiac magnetic resonance (CMR)
      imaging at two tertiary centers between 2007 and 2016 were assessed. Potential
      risk markers, based on history, cardiac magnetic resonance imaging (CMR),
      electrocardiography (ECG) and echocardiography, were analyzed for prediction of
      the primary endpoint of VT, and the secondary endpoint of ATA. During a follow-up
      of 3.5 (0.9-6.1) years, 20 (6.3%) patients reached the primary endpoint, and 30
      (9.4%) the secondary endpoint. Multivariable cox hazards regression identified
      right ventricular (RV) end-diastolic volume (Hazard ratio [HR] 2.03, per 10 ml/m2
      increase; p = 0.02), RV end-systolic volume (HR 3.04, per 10 ml/m2 increase; p =
      0.04), RV mass (HR 1.88, per 10 g/m2 increase; p = 0.02), and RV ejection
      fraction (HR 6.06, per 10% decrease; p = 0.02) derived from CMR to be independent
      risk factors of VT. In addition, QRS-duration (HR 1.70, per 10 ms increase; p =
      0.001) and body mass index (BMI: HR 1.8, per 5 kg/m2 increase; p = 0.02) were
      independent markers of VT. Older age at TOF repair (HR 1.33, per 2 months
      increase; p = 0.03) and BMI (HR 1.76, per 5 kg/m2 increase; p < 0.001)
      independently predicted ATA. RV systolic dysfunction, hypertrophy and dilatation
      on CMR, together with QRS prolongation, and obesity are predictive of VT in TOF
      patients. Older age at TOF repair and obesity were associated with the occurrence
      of ATA.

PMID- 30094563
TI  - Electrophysiological correlates of emotional crossmodal processing in binge
      drinking.
AB  - Emotional crossmodal integration (i.e., multisensorial decoding of emotions) is a
      crucial process that ensures adaptive social behaviors and responses to the
      environment. Recent evidence suggests that in binge drinking-an excessive alcohol
      consumption pattern associated with psychological and cerebral deficits
      crossmodal integration is preserved at the behavioral level. Although some
      studies have suggested brain modifications during affective processing in binge
      drinking, nothing is known about the cerebral correlates of crossmodal
      integration. In the current study, we asked 53 university students (17 binge
      drinkers, 17 moderate drinkers, 19 nondrinkers) to perform an emotional
      crossmodal task while their behavioral and neurophysiological responses were
      recorded. Participants had to identify happiness and anger in three conditions
      (unimodal, crossmodal congruent, crossmodal incongruent) and two modalities (face
      and/or voice). Binge drinkers did not significantly differ from moderate drinkers
      and nondrinkers at the behavioral level. However, widespread cerebral
      modifications were found at perceptual (N100) and mainly at decisional (P3b)
      stages in binge drinkers, indexed by slower brain processing and stronger
      activity. These cerebral modifications were mostly related to anger processing
      and crossmodal integration. This study highlights higher electrophysiological
      activity in the absence of behavioral deficits, which could index a potential
      compensation process in binge drinkers. In line with results found in severe
      alcohol-use disorders, these electrophysiological findings show modified anger
      processing, which might have a deleterious impact on social functioning.
      Moreover, this study suggests impaired crossmodal integration at early stages of
      alcohol-related disorders.

PMID- 30094565
TI  - Presence of aortic root vortex formation after TAVI with CENTERA confirmed using
      4D-flow magnetic resonance imaging.

PMID- 30094567
TI  - Hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies
      using new hybrid CO2 system: preliminary experience in referral center.
AB  - The most frequent peritoneal surface malignancies originate principally by
      gastric cancer, colorectal cancer and ovarian cancer. Apart from the origin,
      peritoneal carcinosis (PC) is considered a negative prognostic factor. The
      hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in the treatment
      of peritoneal malignancies is considered an attractive method to deliver
      chemotherapy with enhanced effect directly at the tumor site. The use of such
      loco-regional approach has proved to improve prognosis of peritoneal
      carcinomatosis from different origins. Recently, new devices are suitable for
      loco-regional intraperitoneal chemotherapy as Peritoneal Recirculation System
      (PRS-1.0 Combat) with CO2 technology. This is a retrospective study with the aim
      to assess the perioperative outcomes using PRS. Seventeen patients were enrolled
      affected by colorectal or ovarian cancer. Complete cytoreduction (RT = 0) was
      achieved for all cases. Median operative time was 420 min (range: 335-665) and
      median drugs dose used for HIPEC was 137 mg/m2 (115-756). Median EBL was 200 ml
      (range 50-1000). Median post-operative hospital stay was 9 days (range: 4-24).
      Treatment-related early complications were recorded in 8 (47.0%) cases and were
      G1-G2 Major complications occurred in two (11.7%) cases. Considering our aim to
      test the PRS in different cases and in different pathologies, the results
      confirmed that the technique is feasible with good perioperative outcomes.

PMID- 30094568
TI  - Evaluation of oncogenic cysteinyl leukotriene receptor 2 as a therapeutic target
      for uveal melanoma.
AB  - Uveal melanoma is a rare, but deadly, form of eye cancer that arises from
      melanocytes within the uveal tract. Although advances have emerged in treatment
      of the primary tumour, patients are still faced with vision loss, eye enucleation
      and lethal metastatic spread of the disease. Approximately 50% of uveal melanoma
      patients develop metastases, which occur most frequently in the liver. Metastatic
      patients encounter an extremely poor prognosis; as few as 8% survive beyond 2
      years. Understanding of the genetic underpinnings of this fatal disease evolved
      in recent years with the identification of new oncogenic mutations that drive
      uveal melanoma pathogenesis. Despite this progress, the lack of successful
      therapies or a proven standard-of-care for uveal melanoma highlights the need for
      new targeted therapies. This review focuses on the recently identified CYSLTR2
      oncogenic mutation in uveal melanoma. Here, we evaluate the current status of
      uveal melanoma and investigate how to better understand the role of this CYSLTR2
      mutation in the disease and implications for patients harbouring this mutation.

PMID- 30094566
TI  - Association with right atrial strain with right atrial pressure: an invasive
      validation study.
AB  - Echocardiographic assessment of right atrial pressure (RAP) from inferior vena
      cava (RAPIVC) dimension may underestimate catheter-derived (RAPC). As right
      atrial (RA) deformation, measured by speckle tracking, is preload-dependent, we
      hypothesized that RA strain may improve estimation of RAPC. Right atrial strain
      components [RA reservoir function (ER), peak RA contraction (ECT) and RA conduit
      function (ECD)] were measured in 125 of 175 patients who had echocardiography and
      invasive measures of RAP (median difference 1 day). To determine whether RA
      strain measures differentiated patients with correct vs incorrect RAPIVC
      assessment, categories with RAPIVC values < 3, 8 and > 15 mmHg were compared with
      RAPC groups < 3, 4-7, 8-10, 11-14 and > 15 mmHg. Non-invasively determined RAP
      was significantly lower (p = 0.001) than invasively determined RAPC, with a weak
      correlation (r = 0.35, p < 0.001). RA strain components were associated with RA
      size, RV function and IVC size. In those with RAPIVC > 15 mmHg, half of patients
      were categorized into RAP < 10 mmHg. There were no significant differences in RA
      characteristics that differentiated patients in whom echocardiographic estimation
      of RAP was inaccurate. Right atrial strain measures were feasible, and had
      associations with RA size, RV systolic function and IVC size. Right atrial strain
      was significantly different between those with normal vs raised pressure, but it
      did not identify those with incorrect echocardiographic assessment of RAP.

PMID- 30094569
TI  - Triumph and tumult of matrix metalloproteinases and their crosstalk with
      eicosanoids in cancer.
AB  - Cancer development and metastasis are associated to perturbation in metabolic
      functions of tumor cells and surrounding inflammatory and stromal cell responses.
      Eicosanoids and lipid mediators, in this regard, attract potential attention
      during cancer development. Eicosanoids, which include prostaglandin,
      prostacyclin, thromboxane, and leukotriene, are synthesized from arachidonic acid
      when cells are stimulated by stress, cytokines, or other growth factors. However,
      the underlying mechanism of eicosanoids in cancer development, specially their
      interactions with proto-oncogene factors in tumor microenvironment, remain
      unexplored. On the other hand, matrix metalloproteinases (MMPs) are a group of
      zinc-dependent endopeptidases which are involved in degradation of different
      extracellular matrix (ECM) proteins. MMPs are associated with different
      physiological responses, including embryogenesis, vasculogenesis, and cellular
      remodeling, as well as different disease pathogenesis. Induced MMP responses are
      especially associated with cancer metastasis and secondary tumor development
      through proteolytic cleavage of several ECM and non-ECM proteins. Although both
      eicosanoids and MMPs are involved with cancer progression and metastasis, the
      interrelation between these two molecules are less explored. The present review
      discusses relevant studies that connect eicosanoids and MMPs and highlight the
      crosstalk between them offering novel therapeutic approach in cancer treatment.

PMID- 30094570
TI  - The roles of the COX2/PGE2/EP axis in therapeutic resistance.
AB  - Therapeutic resistance has been and remains to be the major challenge in
      developing successful treatments for different cancers and therefore,
      understanding the underlying mechanisms in the development of therapeutic
      resistance is crucial in combating cancers. Multiple mechanisms underlie the
      development of therapeutic resistance, and the signaling pathways involved in
      cancer stem cell repopulation, enhanced epithelial-mesenchymal transition (EMT),
      inflammatory infiltration, and immunosuppression play pivotal roles in this
      process. Accumulating evidence indicates that the COX2/PGE2/EP axis plays crucial
      roles not only in tumor development including initiation and progression but also
      in the development of therapeutic resistance. In this review, we will first
      dissect the relationship between the COX2/PGE2/EP axis and therapeutic resistance
      by focusing on the roles of the COX2/PGE2/EP axis in cancer stem cell
      repopulation, EMT, and anti-cancer immunity. Then, we will summarize the
      currently available compounds/drugs targeting each component of this axis as well
      as some of the underlying mechanisms. We hope that better understanding the
      underlying mechanisms of the functional compounds will be helpful in seeking
      additive and/or synergistic effects against therapeutic resistance without or
      with minimal adverse consequence.

PMID- 30094571
TI  - Data Assimilation Methods for Neuronal State and Parameter Estimation.
AB  - This tutorial illustrates the use of data assimilation algorithms to estimate
      unobserved variables and unknown parameters of conductance-based neuronal models.
      Modern data assimilation (DA) techniques are widely used in climate science and
      weather prediction, but have only recently begun to be applied in neuroscience.
      The two main classes of DA techniques are sequential methods and variational
      methods. We provide computer code implementing basic versions of a method from
      each class, the Unscented Kalman Filter and 4D-Var, and demonstrate how to use
      these algorithms to infer several parameters of the Morris-Lecar model from a
      single voltage trace. Depending on parameters, the Morris-Lecar model exhibits
      qualitatively different types of neuronal excitability due to changes in the
      underlying bifurcation structure. We show that when presented with voltage traces
      from each of the various excitability regimes, the DA methods can identify
      parameter sets that produce the correct bifurcation structure even with initial
      parameter guesses that correspond to a different excitability regime. This
      demonstrates the ability of DA techniques to perform nonlinear state and
      parameter estimation and introduces the geometric structure of inferred models as
      a novel qualitative measure of estimation success. We conclude by discussing
      extensions of these DA algorithms that have appeared in the neuroscience
      literature.

PMID- 30094572
TI  - Carbon paste electrodes modified with SnO2/CuS, SnO2/SnS and Cu@SnO2/SnS
      nanocomposites as voltammetric sensors for paracetamol and hydroquinone.
AB  - Several nanocomposites of tin oxide with CuS, SnS or Cu@SnS were prepared and
      used to modify carbon paste electrodes (CPEs). The structure and morphology of
      the materials were studied by XRD and SEM techniques. Cyclic voltammetry and
      electrochemical impedance spectroscopy were applied to investigate their
      electrochemical properties. The modified CPEs exhibit superior voltammetric
      response to paracetamol (PAT) and hydroquinone (HQ) (when compared to a bare CPE)
      in terms of onset oxidation potential and current density. The CPE modified with
      SnO2/SnS was applied to voltammetric determination of PAT (at a working potential
      of 0.55 V versus Ag/AgCl and with a 0.06 MUM detection limit), and of HQ (at 0.39
      V versus Ag/AgCl with a 0.2 MUM detection limit). The voltammetric responses were
      linear in the range from 1.0 to 36 MUM for PAT and from 1.0 to 85 MUM for HQ.
      Graphical abstract Carbon paste electrodes were modified with several new tin
      oxide and sulfidic nanocomposites and then exhibit superior properties in terms
      of detection of paracetamol and hydroquinone.

PMID- 30094574
TI  - From the Editor's Desk.

PMID- 30094575
TI  - In Response to: "The Outcome of Bariatric Surgery in Patients Aged 75 Years and
      Older".

PMID- 30094576
TI  - Reply Letter to the Editor "The Outcome of Bariatric Surgery in Patients Aged 75
      years and Older".

PMID- 30094573
TI  - A novel test for assessment of anterolateral rotatory instability of the knee:
      the tibial internal rotation test (TIR test).
AB  - BACKGROUND: Rotational instability of the knee may persist after anterior
      cruciate ligament (ACL) reconstruction, which may be due to insufficiency of
      anterolateral stabilizing structures. However, no reliable diagnostic tool or
      physical examination test is available for identifying patients with
      anterolateral rotatory instability (ALRI). As shown in cadaveric studies, static
      internal rotation of the knee is increased in higher flexion angles of the knee
      after severing the anterolateral structures. This might also be the case in
      patients with an ACL-deficient knee and concomitant damage to the anterolateral
      structures. The objective of this study is to assess anterolateral rotatory
      instability of the knee during physical examination with a tibial internal
      rotation test. METHODS: ACL-injured knees of 52 patients were examined by two
      examiners and side-to-side differences were compared. Both lower legs were
      internally rotated by applying manual internal rotation torque to both feet in
      prone position with the knees in 30 degrees , 60 degrees  and 90 degrees  of
      flexion. For quantification of the amount of rotation in degrees, a torque
      adapter on a booth was used. Intra-rater, inter-rater and rater-device agreement
      were determined by calculating kappa (kappa) for the tibial internal rotation
      test. RESULTS: Tibial internal rotation is increased in 19.2% of the patients
      with ACL injury according to the tibial internal rotation test. Good intra-rater
      agreement was found for the tibial internal rotation test, kappaC = 0.63 (95%CI 
      0.02-1.28), p = 0.015. Fair inter-rater agreement was found, kappaF = 0.29 (95%CI
      0.02-0.57), p = 0.038. Good rater-device agreement was found, kappaC = 0.62
      (95%CI 0.15-1.10), p = 0.001. CONCLUSION: The tibial internal rotation test shows
      increased tibial internal rotation in a small amount of patients with ACL injury.
      Even though no gold standard for assessment of increased tibial internal rotation
      of the knee is available yet, the test can be of additional value. It can be used
      for assessment of internal rotatory laxity of the knee as part of ALRI in
      addition to the pivot shift test. No clinical implications should yet be based on
      this test alone.

PMID- 30094577
TI  - Conversion of Sleeve Gastrectomy to Roux-en-Y Gastric Bypass.
AB  - INTRODUCTION: A subset of patients undergoing laparoscopic sleeve gastrectomy
      (SG) require eventual conversion to Roux-en-Y gastric bypass (RYGB) due to
      complications from SG or to enhance weight loss. The aim of this study is to
      characterize the indications for conversion and perioperative outcomes in a large
      cohort of these patients at a single institution. METHODS: Patients who underwent
      revisional surgery to convert SG to RYGB at our institution from January 2008
      through January 2017 were retrospectively reviewed. RESULTS: Eighty-nine patients
      with previous SG underwent conversion to RYGB as part of a planned two-stage
      approach to gastric bypass (n = 36), for weight recidivism (n = 11), or for
      complications related to SG (n = 42). Complications from SG that warranted
      conversion included refractory GERD (40.5%), sleeve stenosis (31.0%),
      gastrocutaneous (16.7%), or gastropleural (7.1%) fistula, and gastric torsion
      (4.1%). The mean (SD) age was 47.2 years (11.4 years) and median BMI at the time
      of revision was 43.2 kg/m2. A laparoscopic approach was successfully completed in
      76 patients (85.4%), with an additional of four completed robotically (4.5%). The
      median length of stay was 3 days. Twenty-eight patients (31.5%) had complications
      which included surgical site infection (20.2%), re-operation (6.7%), anastomotic
      stricture (3.4%), and one pulmonary embolism. There were no mortalities with a
      median follow-up of 15 months. CONCLUSIONS: Conversion of SG to RYGB is safe and
      technically feasible when performed for complications of SG or to enhance weight
      loss. This operation can be successfully performed laparoscopically with a low
      rate of conversion and reasonable complication profile.

PMID- 30094578
TI  - The Effects of Laparoscopic Sleeve Gastrectomy on Obesity-Related
      Hypertriglyceridemia-Induced Acute Pancreatitis.
AB  - BACKGROUND: Hypertriglyceridemia-induced acute pancreatitis (HTG-AP) is a
      significant clinical problem and is characterized by high recurrence rate
      compared with non-HTG-AP. The objective of this study was to investigate the
      effects of laparoscopic sleeve gastrectomy (LSG) on obesity-related HTG-AP.
      METHODS: Twenty-nine patients with obesity-related HTG-AP were admitted to our
      hospital and treated with the conventional therapy or LSG surgery according to
      the wishes of patients. Clinical data and the recurrence rate of AP were
      collected at baseline and at four different time points (3, 6, 9, and 12 months)
      after the treatments for all patients. RESULTS: Of the 29 patients, 28 patients
      (19 patients with conventional therapy and 9 patients with LSG surgery) completed
      the 12-month follow-up. Clinical data and the severity scores of AP were
      comparable at baseline when the patients were admitted to the intensive care
      unit. The LSG group experienced a large weight loss (percent total weight loss,
      26.87 +/- 1.44%; percent excess weight loss, 79.56 +/- 1.37%) and triglyceride
      reduction (from 15.77 +/- 1.02 to 1.36 +/- 0.09 mmol/L), and no recurrence was
      observed at 12 months after the surgery. In the conventional treatment group,
      however, body weight was not changed although triglyceride was significantly
      decreased (from 17.34 +/- 1.29 to 8.25 +/- 1.12 mmol/L), and more importantly,
      47.4% of the patients had at least one recurrence of AP in 12 months after the
      treatment. CONCLUSIONS: LSG might be an effective way to cure obesity-related HTG
      induced AP since it prevents the recurrence of this disease. Further randomized
      studies will be needed to standardize this way of treatment.

PMID- 30094579
TI  - Serum Coenzyme Q10 Is Associated with Clinical Neurological Outcomes in Acute
      Stroke Patients.
AB  - Disruption of prooxidant-antioxidant balance may lead to oxidative stress which
      is known as a mechanism contributing to ischemic stroke. Coenzyme Q10 (CoQ10) is
      an endogenous antioxidant that could be effective in preventing oxidative stress.
      However, the contribution of serum levels of CoQ10 in clinical neurological
      outcomes following ischemic stroke has not been clearly established. This study
      aims at measuring serum concentration of CoQ10 along with major indicators of
      antioxidant and oxidant among patients within 24 h after onset of the stroke
      symptoms, and investigating their relation with the clinical status of patients.
      Serum levels of CoQ10, superoxide dismutase (SOD), and malondialdehyde (MDA) were
      measured in 76 patients and 34 healthy individuals. Severity of the neurological
      deficit, functional disability, and cognitive status in ischemic subjects were
      respectively studied with the National Institutes of Health stroke scale (NIHSS),
      modified Rankin Scale (MRS), and Mini-Mental State Examination (MMSE). Stroke
      patients had significantly lower serum level of CoQ10 and SOD as compared to
      controls (27.34 +/- 35.40 ng/ml, 18.58 +/- 0.76 MU/ml, respectively; p < 0.05),
      whereas the serum MDA level was significantly higher (38.02 +/- 2.61 MUm, p <
      0.05). A significant negative correlation was detected between the serum CoQ10
      level and scores of NIHSS and MRS. A similar association was discerned between
      the SOD level and the neurological deficit score. The serum MDA level was also
      found to be strongly correlated with all three neurological scales. These
      findings suggest that the serum level of CoQ10 like other antioxidant and oxidant
      markers can significantly change early after ischemic stroke and they are
      substantially associated with clinical neurological outcomes.

PMID- 30094580
TI  - Altered Notch Signaling in Developing Molar Teeth of Pituitary Adenylate Cyclase
      Activating Polypeptide (PACAP)-Deficient Mice.
AB  - Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with
      neuroprotective and neurotrophic effects. This suggests its influence on the
      development of teeth, which are, similarly to the nervous system, ectoderm and
      neural crest derivatives. Our earlier studies have shown morphological
      differences between wild-type (WT) and PACAP-deficient mice, with upregulated
      sonic hedgehog (SHH) signaling in the lack of PACAP. Notch signaling is a key
      element of proper tooth development by regulating apoptosis and cell
      proliferation. In this study, our main goal was to evaluate the possible effects
      of PACAP on Notch signaling pathway. Immunohistochemical staining was performed
      of Notch receptors (Notch1, 2, 3, 4), their ligands [delta-like protein (DLL)1,
      3, 4, Jagged1, 2], and intracellular target molecules [CSL (CBF1 humans/Su (H)
      Drosophila/LAG1 Caenorhabditis elegans transcription factor); TACE (TNF-alpha
      converting enzyme), NUMB] in molar teeth of 5-day-old WT, and homozygous and
      heterozygous PACAP-deficient mice. We measured immunopositivity in the enamel
      producing ameloblasts and dentin-producing odontoblasts. Notch2 receptor and DLL1
      expression were elevated in ameloblasts of PACAP-deficient mice compared to those
      in WT ones. The expression of CSL showed similar results both in the ameloblasts
      and odontoblasts. Jagged1 ligand expression was elevated in the odontoblasts of
      homozygous PACAP-deficient mice compared to WT mice. Other Notch pathway elements
      did not show significant differences between the genotype groups. The lack of
      PACAP leads to upregulation of Notch pathway elements in the odontoblast and
      ameloblast cells. The underlying molecular mechanisms are yet to be elucidated;
      however, we propose SHH-dependent and independent processes. We hypothesize that
      this compensatory upregulation of Notch signaling by the lack of PACAP could
      represent a salvage pathway in PACAP-deficient animals.

PMID- 30094581
TI  - A paper-based photothermal array using Parafilm to analyze hyperthermia response
      of tumour cells under local gradient temperature.
AB  - Temperature is a critical extrinsic physical parameter that determines cell fate.
      Hyperthermia therapy has become an efficient treatment for tumor ablation. To
      understand the response of tumor cells under thermal shocks, we present a paper
      based photothermal array that can be conveniently coupled with commercial 96-well
      cell culture plates. This paper chip device was fabricated in one step using
      Parafilm(r) and Kimwipers(r) based on a heat lamination strategy. Liquid was
      completely adsorbed and confined within the cellulose fibres of hydrophilic
      regions. Then, Prussian blue nanoparticles (PB NPs) as the photothermal initiator
      were introduced into the loading wells, and thermal energy was generated via near
      infrared (NIR) laser irradiation. After assembling the paper device with a 96
      well plate, the temperature of each well could be individually controlled by
      varying the loading amount of PB NPs and laser irradiation time. As a proof-of
      concept study, the effects of local thermal shocks on HeLa cells were
      investigated using MTT cell viability assay and Live/Dead cell staining. The
      variation of cell viability could be monitored in situ with controllable
      temperature elevation. The proposed paper photothermal array loaded with thermal
      initiators represents an enabling tool for investigating the hyperthermia
      responses of biological cells. Moreover, the facile fabrication technique for
      paper patterning is advantageous for customizing high-throughput microfluidic
      paper-based analytical devices (MUPADs) with extremely low cost.

PMID- 30094582
TI  - Macropored microparticles with a core-shell architecture for oral delivery of
      biopharmaceuticals.
AB  - Microparticles (MPs) have been extensively researched as a potential drug
      delivery vehicle. Here, we investigated the fabrication of MPs with pH-responsive
      macropores and evaluated their potential applicability in developing solid oral
      drug formulations. Our previous study showed that macropored MPs, made of
      Eudragit(r) L100-55, could encapsulate 100 nm, 1 um, and 4 um sized fluorescent
      beads-model drugs that are mimicking vaccines, bacteria, and cells. In the
      present study, closed-pored MPs after freeze-drying were coated with a gastric
      soluble Eudragit(r) EPO layer to protect MPs in the simulated pregastric
      environment. Subsequently, drug encapsulated MPs maintained their intact closed
      pored structure in the simulated gastric environment and exhibited a rapid
      release in the simulated intestine environment. Our MP system was found to
      provide a significantly higher level of protection to the encapsulated lactase
      enzyme compared to the control sample (i.e. without using MPs). Real-time
      fluorescence microscopy analysis showed that macropored MPs released encapsulated
      drugs in a burst-release pattern and in a size-independent manner. This work
      shows that our proposed EPO-coated MPs with pH-responsive macropores can meet the
      challenges posed by the multiple physiological environments of the digestive
      tract and be used in developing highly effective solid oral drug/vaccine
      formulations.

PMID- 30094583
TI  - Risk factors associated with reproductive performance in small-scale dairy farms
      in Mexico.
AB  - Several studies suggest that reproductive performance in small-scale dairy farms
      is low reducing the farms' profitability. Therefore, identifying risk factors
      associated with low reproductive performance is a key step to implement an
      improved reproductive management program. Accordingly, the aim of the present
      study was to identify the main risk factors affecting the reproductive
      performance of cows in small-scale dairy farms. Ninety-six dairy farms were
      incorporated into this study, and data from 1263 lactations were collected with
      different events as potential risk factors. Logistic regression models were used
      to assess the association (odds ratio, OR) and impact (population attributable
      fraction, PAF) between the potential risk factors and the reproductive variables.
      The main risk factors associated with assisted calving were male calf and
      primiparous cows (OR = 1.7, PAF = 0.315 and OR = 1.5, PAF = 0.131, respectively),
      while for retained fetal membranes (RFM) were assisted calving and abortion (OR =
      4.5, PAF = 0.440 and OR = 8.1, PAF = 0.239, respectively). The main risk factors
      for days to first service over 70 days in milk were low body condition score at
      calving (BCS <= 2.5) and primiparous cows (OR = 2.2, PAF = 0.285 and OR = 1.4;
      PAF = 0.096, respectively), while for days open over 110 days in milk were low
      BCS at calving (BCS <= 2.5) and primiparous cows (OR = 1.7, PAF = 0.213 and OR =
      1.4; PAF = 0.096, respectively) The main risk factor for non-pregnant cows at
      first service was RFM (OR = 1.7; PAF = 0.059). In conclusion, assisted calving,
      male calf, BCS <= 2.5 and RFM were the main risk factors associated with reduced
      reproductive performance in small-scale dairy farms in tropical and subtropical
      regions of Mexico.

PMID- 30094585
TI  - Investigation of intraoperative dosing patterns of neuromuscular blocking agents.
AB  - There is a growing body of literature documenting the use of deep neuromuscular
      block (NMB) during surgery. Traditional definitions of depth of NMB rely on train
      of-four assessment, which can be less reliable in retrospective studies. The goal
      of our study was to investigate the real-world practice pattern of dosing of
      neuromuscular blocking agents (NMBA), utilizing the amount of NMBA used during
      the course of a case, adjusted for patient weight and case duration, as a
      surrogate measure of depth of NMB. We also aimed to identify case factors
      associated with larger NMBA doses. In this retrospective observational analysis
      of our anesthesia information management system, we analyzed all general
      endotracheal anesthesia cases from 2012 to 2015 in which an intermediate-acting
      NMBA was used. Cases using a long-acting NMBA or only succinylcholine were
      excluded. The expected duration of the case was calculated based on the
      cumulative dose of NMB used, normalized to the patient's ideal body weight and
      the ED95 of the drug. If the expected duration of the case was greater than the
      actual case duration documented in the case record, it was classified as higher
      dosing (HD). If the expected duration was equal to or less than the actual
      duration, it was considered predicted dosing (PD). Categorical comparisons
      between HD and PD groups were made for various patient, procedural, and provider
      factors. 72,684 cases were included in the final analysis, of which 46,358, or
      64% of cases, used HD. Cases with patients who were morbidly obese, younger than
      65 years, and who were lower ASA Physical Status classification (I or II) used
      more HD as opposed to PD. Cases that were non-open, used total intravenous
      anesthesia, emergent cases, or used non-rapid sequence anesthesia induction had
      higher rates of HD than their matched counterparts. All results were
      statistically significant. HD was more common in cases that documented train-of
      four and used the reversal agent neostigmine. Approximately two-thirds of general
      endotracheal anesthesia cases using an intermediate-acting NMBA used HD. Cases
      with higher rates of HD may be those that are traditionally technically complex
      or emergent, would benefit from greater paralysis, or do not use adjunctive
      medications for muscle relaxation. Age greater than 65 years was shown to have
      lower rates of HD, likely due to provider awareness of age-related changes in
      pharmacokinetics and pharmacodynamics. Intraoperative monitoring and NMB
      antagonism with neostigmine were used more frequently with HD.

PMID- 30094584
TI  - Women With Mental Illness Seeking Assisted Reproduction Considerations in Ethical
      Candidate Selection.
AB  - PURPOSE OF REVIEW: This review aims to provide guidance to clinicians facing
      requests for assisted reproduction from women with mental illness. RECENT
      FINDINGS: The paper explores the clinical and safety aspects of initiating
      fertility treatment in this context, including the use of psychotropic medication
      and the risk of untreated psychiatric mood or psychotic disorders. It also
      presents the ethical considerations involved in candidate selection, including
      treating similar cases equitably to avoid biased decisions based solely on "gut
      feelings," respect for women's reproductive autonomy, and an effort to protect
      patients and prospective fetuses/children from harm by employing optimal
      strategies regarding medication and psychosocial support. Clinicians ought to be
      informed regarding recent evidence related to the safety and efficacy of
      psychopharmacologic treatment of women during pregnancy and the post-partum. They
      should also carry out a thoughtful ethical analysis to ensure minimal violation
      of women's reproductive autonomy.

PMID- 30094587
TI  - Correction to: Down from the treetops: red langur (Presbytis rubicunda)
      terrestrial behavior.
AB  - In the original publication of this article, the Table 2 was published
      incorrectly. The revised Table 2 is given on the following page.

PMID- 30094586
TI  - The IMPDH inhibitors, ribavirin and mycophenolic acid, inhibit peste des petits
      ruminants virus infection.
AB  - Peste des petits ruminants virus (PPRV) causes highly contagious diseases in
      domestic and particular wild small ruminants, leading to substantial economic
      loss. The development of effective and cheap antiviral medications shall help to
      circumvent this emerging burden. In this study, we found that ribavirin, a
      competitive inosine-5'-monophosphate dehydrogenase (IMPDH) inhibitor,
      significantly inhibits the replication of PPRV. As IMPDH is a key enzyme in
      purine nucleotide synthesis, supplementation of exogenous guanosine attenuate the
      anti-PPRV effect of ribavirin. Interestingly, an uncompetitive IMPDH inhibitor,
      mycophenolic acid (MPA), exerted more potent antiviral effect again PPRV.
      Similarly, this effect was largely restored upon supplementation of guanosine.
      Thus, we have demonstrated that the IMPDH inhibitors ribavirin and MPA combat
      PPRV infection through purine nucleotide depletion. Because both regimens have
      been widely used in the clinic for treating viral infection or organ rejection in
      transplantation patients for decades, respectively, repurposing these existing
      safe and cheap medications may provide a new avenue for combating PPRV infection.

PMID- 30094588
TI  - The status and distribution of PCBs along the coast of Vietnam.
AB  - Polychlorinated biphenyls (PCBs), well-known as an important scientific
      achievement, are now considered as one of the most persistent organic pollutants
      (POPs) that need to be strictly controlled and forbidden worldwide (the Stockholm
      convention on POPs). Vietnam is one of the countries that encounters with serious
      issues from PCB contamination. This study presented a comprehensive review on the
      status and contamination of PCBs along the coast of Vietnam. The contaminated
      PCBs data in the water, sediment and biological samples from 18 provinces along
      Vietnam coastline were collected from various sources. A comparison in PCBs
      contamination between Vietnam and other Asian countries was included. The status
      on PCBs contamination in Vietnam since participated as a party of the Stockholm
      convention on POPs in 2002 was also assessed. The results showed that Vietnam is
      facing serious PCBs contamination problems as it evidences the spread and
      accumulation of PCBs in the marine environment. The implementation of the
      Stockholm convention on POPs (PCBs in particular) has not yet demonstrated
      significant effect on the reduction in PCBs contamination in the environment.
      This information on PCBs contamination in Vietnam urges government to strengthen
      the mechanism, policy and legislation, the management capacity for PCBs as well
      as applying advanced and modern technologies in reducing, disposing and
      eliminating PCBs from the environment.

PMID- 30094589
TI  - Evidence for complete nitrification in enrichment culture of tidal sediments and
      diversity analysis of clade a comammox Nitrospira in natural environments.
AB  - Complete ammonia oxidizers (comammox), as novel microbial communities, are
      predicted to play an important role in the nitrogen cycle. Here we reported the
      presence of complete nitrification in tidal sediments and examined the diversity
      and abundance of comammox in natural ecosystems. Metagenome and metatranscriptome
      of the enrichment culture from tidal sediments harbored the genes of comammox.
      Near-complete comammox AmoA/B/C- and Hao-like sequences showed close
      relationships to the known comammox (with sequence identity from 79 to 99%)
      rather than classical betaproteobacterial ammonia-oxidizing bacteria (beta-AOB)
      (57 to 66%) and ammonia-oxidizing archaea (AOA) (24 to 38%). To analyze the
      diversity of comammox in natural environments, a new primer set targeting clade A
      comammox Nitrospira (COM-A) amoA genes was designed based on sequences obtained
      in this study and sequences from published database. In silico evaluation of the
      primers showed the high coverage of 89 and 100% in the COM-A amoA database.
      Application of the primers in six different ecosystems proved their strong
      availability. Community composition of COM-A suggested a relatively higher
      diversity than beta-AOB in similar environments. Quantification results showed
      that COM-A amoA genes accounted for about 0.4-5.6% in total amoA genes. These
      results provide novel insight into our perception of the enigmatic comammox and
      have significant implications for profound understanding of complex nitrification
      process.

PMID- 30094591
TI  - Friction Cost Estimates of Productivity Costs in Cost-of-Illness Studies in
      Comparison with Human Capital Estimates: A Review.
AB  - Cost-of-illness (COI) studies often include the 'indirect' cost of lost
      production resulting from disease, disability, and premature death, which is an
      important component of the economic burden of chronic conditions assessed from
      the societal perspective. In most COI studies, productivity costs are estimated
      primarily as the economic value of production forgone associated with loss of
      paid employment (foregone gross earnings); some studies include the imputed value
      of lost unpaid work as well. This approach is commonly but imprecisely referred
      to as the human capital approach (HCA). However, there is a lack of consensus
      among health economists as to how to quantify loss of economic productivity. Some
      experts argue that the HCA overstates productivity losses and propose use of the
      friction cost approach (FCA) that estimates societal productivity loss as the
      short-term costs incurred by employers in replacing a lost worker. This review
      sought to identify COI studies published during 1995-2017 that used the FCA, with
      or without comparison to the HCA, and to compare FCA and HCA estimates from those
      studies that used both approaches. We identified 80 full COI studies (of which
      75% focused on chronic conditions), roughly 5-8% of all COI studies. The majority
      of those studies came from three countries, Canada, Germany, and the Netherlands,
      that have officially endorsed use of the FCA. The FCA results in smaller
      productivity loss estimates than the HCA, although the differential varied widely
      across studies. Lack of standardization of HCA and FCA methods makes productivity
      cost estimates difficult to compare across studies.

PMID- 30094594
TI  - Pyogenic granuloma of the ampulla of Vater: unexpected cause of gastrointestinal
      bleeding.
AB  - We describe the case of a previously healthy 8-year-old girl presenting with a 1
      year history of iron deficiency anemia. There was no report of hematemesis,
      abdominal pain or melena. Laboratory work-up excluded iron malabsorption as the
      underlying cause. Therefore, endoscopic evaluation was performed to exclude
      gastrointestinal blood loss, which revealed the presence of a 7 mm reddish lesion
      located within the ampulla of Vater. Capsule endoscopy excluded alternative
      diagnoses and concomitant lesions. Histopathological examination confirmed the
      diagnosis of pyogenic granuloma. The young age of the child and the benign nature
      of this lesion along with the absence of complications favored conservative
      management. Pyogenic granuloma is a benign vascular lesion that presents as a
      polypoid red mass. In the gastrointestinal tract, it is a rare condition and
      occurs more commonly in the elderly. The most common sites are the small
      intestine, esophagus, and colon, but they can occur throughout the entire
      gastrointestinal tract with a propensity to bleed that may cause iron deficiency
      anemia. In pediatric age patients, there are few reports of gastrointestinal
      pyogenic granulomas, most of which occur in the colon and rectum. Its
      identification and location in the ampulla of Vater is an exceptional finding.

PMID- 30094590
TI  - Heparin: role in protein purification and substitution with animal-component free
      material.
AB  - Heparin is a highly sulfated polysaccharide which belongs to the family of
      glycosaminoglycans. It is involved in various important biological activities.
      The major biological purpose is the inhibition of the coagulation cascade to
      maintain the blood flow in the vasculature. These properties are employed in
      several therapeutic drugs. Heparin's activities are associated with its
      interaction to various proteins. To date, the structural heparin-protein
      interactions are not completely understood. This review gives a general overview
      of specific patterns and functional groups which are involved in the heparin
      protein binding. An understanding of the heparin-protein interactions at the
      molecular level is not only advantageous in the therapeutic application but also
      in biotechnological application of heparin for downstreaming. This review focuses
      on the heparin affinity chromatography. Diverse recombinant proteins can be
      successfully purified by this method. While effective, it is disadvantageous that
      heparin is an animal-derived material. Animal-based components carry the risk of
      contamination. Therefore, they are liable to strict quality controls and the
      validation of effective good manufacturing practice (GMP) implementation. Hence,
      adequate alternatives to animal-derived components are needed. This review
      examines strategies to avoid these disadvantages. Thereby, alternatives for the
      provision of heparin such as chemical synthesized heparin, chemoenzymatic
      heparin, and bioengineered heparin are discussed. Moreover, the usage of other
      chromatographic systems mimetic the heparin effect is reviewed.

PMID- 30094595
TI  - Fluorescence-guided selective arterial clamping during RAPN provides better early
      functional outcomes based on renal scan compared to standard clamping.
AB  - To compare the functional and operative outcomes of robot-assisted partial
      nephrectomy with selective arterial clamping guided by near infrared fluorescence
      imaging (NIRF-RAPN) versus a cohort of patients who underwent standard RAPN
      without selective arterial clamping (S-RAPN). 62 consecutive patients underwent
      RAPN from January 2016 to May 2017: the last 20 patients underwent NIRF-RAPN.
      Preoperative and postoperative renal scan at 1 month were performed to evaluate
      the glomerular filtration rate (GFR) of the operated renal unit and total
      function. Functional and operative outcomes of cases were compared with a cohort
      of 42 patients undergoing S-RAPN. Selective clamping was performed in 15 patients
      (75%), whereas five (25%) cases were converted to S-RAPN, due to incomplete
      ischemic appearance of the tumor after selective clamping. Median tumor diameter
      was 40 mm in both groups. Median selective clamping was 24 min in both groups.
      Operative time (206' vs 190') and blood loss (200 vs 170 cc) were comparable. No
      major complications have been reported in the NIRF-RAPN group, whereas three
      acute hemorrhages with embolization were found in the S-RAPN group. The analysis
      of renal scan data revealed that a greater loss of GFR in the operated renal unit
      was observed after S-RAPN compared to NIRF-RAPN [21.5% vs. 5.5%; p = 0.046], as
      well as total GFR loss [8% vs 0%; p = 0.007]. The use of NIRF imaging was
      associated with improved short-term renal functional outcomes compared to RAPN
      without selective arterial clamping. To our knowledge, this is the first
      comparative study analyzing the GFR obtained from renal scan.

PMID- 30094593
TI  - The Intersection of Sex Differences, Tobacco Use, and Inflammation: Implications
      for Psychiatric Disorders.
AB  - PURPOSE OF REVIEW: Tobacco use, sex differences, and psychiatric disorders are
      associated with altered immune function. There are also sex differences in
      tobacco use and psychiatric disorders. This review summarizes findings from the
      small, but growing literature examining sex differences in the effects of tobacco
      use on inflammation and the implications for psychiatric disorders. RECENT
      FINDINGS: We identified four studies that tested the interaction between sex and
      tobacco/nicotine on inflammation. Although males and females generally exhibited
      differential tobacco-induced immune responses, the pattern varied depending on
      the sample (rodents vs. humans) and the method to evaluate inflammation. Evidence
      suggests that sex modulates the effects of tobacco smoke on inflammation. Many
      inflammation markers associated with sex differences and tobacco use are related
      to psychiatric disorders. We propose a model in which sex, tobacco use, and
      inflammation interact to increase risk for psychiatric disorders. Future studies
      are needed to examine the mechanisms that explain this relationship.

PMID- 30094596
TI  - Correction to: Risk factors for increased left ventricular hypertrophy in
      patients with chronic kidney disease: findings from the CKD-JAC study.
AB  - In the original publication, there were several errors identified after online
      publication.

PMID- 30094597
TI  - Non-invasive assessment of endarteritis in Marfan syndrome with aortic dissection
      after surgical treatment.

PMID- 30094592
TI  - Breast ultrasound: recommendations for information to women and referring
      physicians by the European Society of Breast Imaging.
AB  - : This article summarises the information that should be provided to women and
      referring physicians about breast ultrasound (US). After explaining the physical
      principles, technical procedure and safety of US, information is given about its
      ability to make a correct diagnosis, depending on the setting in which it is
      applied. The following definite indications for breast US in female subjects are
      proposed: palpable lump; axillary adenopathy; first diagnostic approach for
      clinical abnormalities under 40 and in pregnant or lactating women; suspicious
      abnormalities at mammography or magnetic resonance imaging (MRI); suspicious
      nipple discharge; recent nipple inversion; skin retraction; breast inflammation;
      abnormalities in the area of the surgical scar after breast conserving surgery or
      mastectomy; abnormalities in the presence of breast implants; screening high-risk
      women, especially when MRI is not performed; loco-regional staging of a known
      breast cancer, when MRI is not performed; guidance for percutaneous interventions
      (needle biopsy, pre-surgical localisation, fluid collection drainage); monitoring
      patients with breast cancer receiving neo-adjuvant therapy, when MRI is not
      performed. Possible indications such as supplemental screening after mammography
      for women aged 40-74 with dense breasts are also listed. Moreover, inappropriate
      indications include screening for breast cancer as a stand-alone alternative to
      mammography. The structure and organisation of the breast US report and of
      classification systems such as the BI-RADS and consequent management
      recommendations are illustrated. Information about additional or new US
      technologies (colour-Doppler, elastography, and automated whole breast US) is
      also provided. Finally, five frequently asked questions are answered. TEACHING
      POINTS: * US is an established tool for suspected cancers at all ages and also
      the method of choice under 40. * For US-visible suspicious lesions, US-guided
      biopsy is preferred, even for palpable findings. * High-risk women can be
      screened with US, especially when MRI cannot be performed. * Supplemental US
      increases cancer detection but also false positives, biopsy rate and follow-up
      exams. * Breast US is inappropriate as a stand-alone screening method.

PMID- 30094598
TI  - Fluoride imaging of atherosclerotic plaques: Moving from macro to
      microcalcifications?

PMID- 30094600
TI  - Inhibition of mitophagy decreases survival of Caenorhabditis elegans by
      increasing protein aggregation.
AB  - Autophagy of mitochondria, i.e., mitophagy, plays a crucial role in coping with
      stressors in the aging process, metabolic disturbances, and neurological
      disorders. Impairments of the process might consequently lead to enhanced
      accumulation of aged and aggregated proteins and reduced cellular integrity in
      response to stress. In the present study, we used the stress-sensitive mutant mev
      1 of Caenorhabditis elegans to assess the effects of the knockdown of mitophagy
      relevant genes on survival under heat stress, the amount of autophagosomes, and
      on protein aggregation. RNA interference for dct-1, drp-1, eat-3, fis-1, fzo1,
      glb-1, pink-1, and pgam-5 all resulted in a significant reduction of survival
      time at 37  degrees C. These effects were associated with a decrease in
      autophagosomal flux of proteins, as indicated by increased accumulation of GFP
      tagged SQST-1, and a reduced amount of lysosomes demonstrating that autophagy was
      hampered. Moreover, the gene knockdowns led to increased levels of reactive
      oxygen species in mitochondria and an enhanced protein aggregation. In
      conclusion, our studies show that mitophagy is of central importance to keep
      mitochondria functional in order to prevent production of excess reactive oxygen
      species and protein aggregation and finally a reduction of survival under heat
      stress.

PMID- 30094599
TI  - Preparation of menisdaurigenin and related compounds.
AB  - Menisdaurin (1), a cyano glucoside, was first isolated in 1978 from Menispermum
      dauricum (Menispermaceae) and named after the plant. It has been also isolated
      from several plant sources. The stereochemistry of the aglycone part was first
      reported as (Z,4R,6S)-enantiomer of (4,6-dihydroxy-2-cyclohexen-1
      ylidene)acetonitrile based on the CD spectrum of menisdaurilide (2), the
      alpha,beta-unsaturated gamma-lactone obtained by an acid hydrolysis of
      menisdaurin. Later, the absolute stereochemistry was revised as (Z,4S,6R) by X
      ray crystal analysis of 1 isolated from Saniculiphyllum guangxiens. The aglycone
      part of menisdaurin (1) has not been obtained from 1, because an acid hydrolysis
      of 1 gave menisdaurilide (2), and enzymatic hydrolysis with emulsin did not give
      the aglycone. On the other hand, a compound named coculauril (3) was isolated
      from Cocculus lauriforius. This compound has the same planner structure
      corresponding to the aglycone of 1, but the stereochemistry was reported to be
      (E,4R,6S). Here, we confirmed the absolute stereochemistry of 1 by Mosher's
      method to be (Z,4S,6R), and prepared the aglycone of 1, i.e., menisdaurigenin (4)
      by an enzymatic hydrolysis of 1. We also revealed that 4 is a different compound
      from 3 and unstable in water and MeOH.

PMID- 30094601
TI  - High-fat diet abolishes the cardioprotective effects of ischemic postconditioning
      in murine models despite increased thioredoxin-1 levels.
AB  - Ischemic postconditioning (PostC) reduces infarct size in healthy experimental
      models. However, if protective effects of PostC are abolished during early stages
      of atherosclerotic and if this is related with a disbalance in mitochondrial
      energetics and alterations in thioredoxin-1 (Trx1) is still unknown. The
      objectives were to generate a murine high-fat diet (HFD)-fed model that developed
      in a phenotype consistent with early stages of atherosclerosis to then evaluate
      whether HFD exposure increased oxidative stress and consequently abolished the
      cardioprotection conferred by PostC. We used C57/BL6 mice fed with control diet
      (CD) or HFD for 12 weeks. Isolated mice hearts were subjected to 30 min of
      ischemia and 120 min of reperfusion (I/R group). For PostC group, after ischemia,
      six cycles of reperfusion/ischemia were performed (10 s per cycle) at the onset
      of reperfusion. In CD group, the PostC reduced infarct size (CD-I/R: 52.14 +/-
      2.8 vs. CD-PostC: 36.58 +/- 1.8, P < 0.05) and increased phosphorylation of
      GSK3beta (CD-PostC: 2.341 +/- 1.03 vs. CD-Baseline: 0.923 +/- 0.41 AUOD, P <
      0.05), and this cardioprotection was abolished in HFD-exposed mice. HFD increased
      hydrogen peroxide levels, produced a shift towards an oxidized intracellular
      environment (GSSG/GSH2), and increased Trx1 expression with higher fractions of
      oxidized protein. State 3 mitochondrial oxygen consumption in basal conditions
      decreased 24% in HFD-exposed mice and PostC improved state 3 values only in CD
      mice. Cellular redox state and mitochondrial bioenergetics were altered in HFD
      exposed mice. We demonstrated that alterations in redox state at early stages of
      atherosclerosis abolished cardioprotective mechanisms, such as those induced by
      PostC, even with increased Trx1 levels.

PMID- 30094602
TI  - Synthesis of Ionic Liquids Originated from Natural Products.
AB  - In this chapter, preparation, basic properties, and some applications of ionic
      liquids composed of naturally-derived ions are summarized. There are many
      candidate ions in nature suitable for ionic liquid preparation. Physicochemical
      properties and preparation of some ionic liquids based on carboxylate anions,
      cholinium cation, and even amino acids are mentioned. Some interesting
      applications based on these ionic liquids composed of naturally-derived ions are
      also briefly introduced. Graphical Abstract.

PMID- 30094603
TI  - Contextual modulation of prime response retrieval processes: Evidence from
      auditory negative priming.
AB  - Contextual similarity between learning and test phase has been shown to be
      beneficial for memory retrieval. Negative priming is known to be caused by
      multiple processes; one of which is episodic retrieval. Therefore, the contextual
      similarity of prime and probe presentations should influence the size of the
      negative priming effect. This has been shown for the visual modality. In
      Experiment 1, an auditory four-alternative forced choice reaction time task was
      used to test the influence of prime-probe contextual similarity on negative
      priming and the processes underlying the modulation by context. The negative
      priming effect was larger when the auditory context was repeated than when it was
      changed from prime to probe. The modulation by context was exclusively caused by
      an increase in prime response retrieval errors in ignored repetition trials with
      context repetition, whereas repeating only the context but not the prime
      distractor did not lead to an increase in prime response retrieval. This exact
      pattern of results was replicated in Experiment 2. The findings suggest that
      contextual information is integrated with prime distractor and response
      information. Retrieval of the previous episode, including prime distractor, prime
      response, and context (event file), can be triggered when the former prime
      distractor is repeated, whereas a context cue alone does not retrieve the event
      file. This suggests an event file structure that is more complicated than its
      usually assumed binary structure.

PMID- 30094604
TI  - Fast prenatal development of the NPY neuron system in the neocortex of the
      European wild boar, Sus scrofa.
AB  - Knowledge on cortical development is based mainly on small rodents besides
      primates and carnivores, all being altricial nestlings. Ungulates are precocial
      and born with nearly mature sensory and motor systems. Almost no information is
      available on ungulate brain development. Here, we analyzed European wild boar
      cortex development, focusing on the neuropeptide Y immunoreactive (NPY-ir) neuron
      system in dorsoparietal cortex from E35 to P30. Transient NPY-ir neuron types
      including archaic cells of the cortical plate and axonal loop cells of the
      subplate which appear by E60 concurrent with the establishment of the ungulate
      brain basic sulcal pattern. From E70, NPY-ir axons have an axon initial segment
      which elongates and shifts closer towards the axon's point of origin until P30.
      From E85 onwards (birth at E114), NPY-ir neurons in cortical layers form basket
      cell-like local and Martinotti cell-like ascending axonal projections. The mature
      NPY-ir pattern is recognizable at E110. Together, morphologies are conserved
      across species, but timing is not: in pig, the adult pattern largely forms
      prenatally.

PMID- 30094605
TI  - PLP1 and CNTN1 gene variation modulates the microstructure of human white matter
      in the corpus callosum.
AB  - The corpus callosum is the brain's largest commissural fiber tract and is crucial
      for interhemispheric integration of neural information. Despite the high
      relevance of the corpus callosum for several cognitive systems, the molecular
      determinants of callosal microstructure are largely unknown. Recently, it was
      shown that genetic variations in the myelin-related proteolipid 1 gene PLP1 and
      the axon guidance related contactin 1 gene CNTN1 were associated with differences
      in interhemispheric integration at the behavioral level. Here, we used an
      innovative new diffusion neuroimaging technique called neurite orientation
      dispersion and density imaging (NODDI) to quantify axonal morphology in
      subsections of the corpus callosum and link them to genetic variation in PLP1 and
      CNTN1. In a cohort of 263 healthy human adults, we found that polymorphisms in
      both PLP1 and CNTN1 were significantly associated with callosal microstructure.
      Importantly, we found a double dissociation between gene function and
      neuroimaging variables. Our results suggest that genetic variation in the myelin
      related gene PLP1 impacts white matter microstructure in the corpus callosum,
      possibly by affecting myelin structure. In contrast, genetic variation in the
      axon guidance related gene CNTN1 impacts axon density in the corpus callosum.
      These findings suggest that PLP1 and CNTN1 gene variations modulate specific
      aspects of callosal microstructure that are in line with their gene function.

PMID- 30094606
TI  - Radial glial elements in the cerebral cortex of the lesser hedgehog tenrec.
AB  - We investigated astroglial cells in several areas of the telencephalic cortex of
      the lesser hedgehog tenrec (Echinops telfairi). Compared to other mammals, the
      cortex of the tenrec has a relatively large paleocortex and a low encephalization
      index. We stained sections from tenrec forebrains with structural and functional
      glia markers focusing on selected cortical areas, the paleocortex, rhinal cortex,
      neocortex and the dentate gyrus of the hippocampal formation. We found that in
      all parts of the tenrec forebrain cortex, radial processes exist which are
      positive for glial fibrillary acidic protein (GFAP) although with differential
      localization: in the rhinal cortex and neocortical region radial glial fibers are
      located in the subventricular regions, whereas in the dentate gyrus and
      paleocortex they appear to arise from the cells in the respective granular
      layers. The relatively high abundance of the radial fibers in layer III of the
      paleocortex was very conspicuous. Only few of these radial processes were also co
      labeled with doublecortin (DCX), yet most of the DCX-positive cells were negative
      for GFAP. The GFAP-positive radial fibers were in turn neither positive for
      glutamine synthetase, nor did they show immunoreactivity for the astroglia
      specific water channel aquaporin-4 (AQP4). Star-shaped astrocytes, however,
      displayed the typical perivascular and subpial expression patterns for AQP4. We
      conclude that the radial glia in the adult tenrec represents an immature form of
      astroglia that persists in these animals throughout life.

PMID- 30094607
TI  - Interactive histogenesis of axonal strata and proliferative zones in the human
      fetal cerebral wall.
AB  - Development of the cerebral wall is characterized by partially overlapping
      histogenetic events. However, little is known with regards to when, where, and
      how growing axonal pathways interact with progenitor cell lineages in the
      proliferative zones of the human fetal cerebrum. We analyzed the developmental
      continuity and spatial distribution of the axonal sagittal strata (SS) and their
      relationship with proliferative zones in a series of human brains (8-40 post
      conceptional weeks; PCW) by comparing histological, histochemical, and
      immunocytochemical data with magnetic resonance imaging (MRI). Between 8.5 and 11
      PCW, thalamocortical fibers from the intermediate zone (IZ) were initially
      dispersed throughout the subventricular zone (SVZ), while sizeable axonal
      "invasion" occurred between 12.5 and 15 PCW followed by callosal fibers which
      "delaminated" the ventricular zone-inner SVZ from the outer SVZ (OSVZ). During
      midgestation, the SS extensively invaded the OSVZ, separating cell bands, and a
      new multilaminar axonal-cellular compartment (MACC) was formed. Preterm period
      reveals increased complexity of the MACC in terms of glial architecture and the
      thinning of proliferative bands. The addition of associative fibers and the
      formation of the centrum semiovale separated the SS from the subplate. In vivo
      MRI of the occipital SS indicates a "triplet" structure of alternating
      hypointense and hyperintense bands. Our results highlighted the developmental
      continuity of sagittally oriented "corridors" of projection, commissural and
      associative fibers, and histogenetic interaction with progenitors, neurons, and
      glia. Histogenetical changes in the MACC, and consequently, delineation of the SS
      on MRI, may serve as a relevant indicator of white matter microstructural
      integrity in the developing brain.

PMID- 30094608
TI  - Short-term association between outdoor air pollution and osteoporotic hip
      fracture.
AB  - : This study examines the association of the levels of different airborne
      pollutants on the incidence of osteoporotic hip fracture in a southern European
      region. Association was detected between SO2 and NO2 and hospital admissions due
      to hip fracture. INTRODUCTION: To examine the short-term effects of outdoor air
      pollution on the incidence of osteoporotic hip fracture in a southern European
      region. METHODS: This is an ecological retrospective cohort study based on data
      obtained from three databases. In a time-series analysis, we examined the
      association between hip fracture incidence and different outdoor air pollutants
      (sulfur dioxide (SO2), monoxide (NO), nitrogen dioxide (NO2), ozone (O3), and
      particulate matter in suspension < 2.5 (PM2.5) and < 10-MUm (PM10) conditions by
      using general additive models (Poisson distribution). The incidence rate ratio
      (IRR), crude and adjusted by season and different weather conditions, was
      estimated for all parameters. Hip incidence was later analyzed by sex and age
      (under or over age 75) subgroups. The main outcome measure was daily hospital
      admissions due to fracture. RESULTS: Hip fracture incidence showed association
      with SO2 (IRR 1.11 (95% CI 1.04-1.18)), NO (IRR 1.01 (95% CI 1.01-1.02)), and NO2
      (IRR 1.02 (95% CI 1.01-1.04)). For O3 levels, this association was negative (IRR
      0.97 (95% CI 0.95-0.99)). The association persisted for SO2 and NO2 when the
      models were adjusted by season. After adjusting by season and weather conditions,
      the association persisted for NO2. When participants were stratified by age and
      sex, associations persisted only in women older than 75 years. CONCLUSIONS: A
      short-term association was observed with several indicators of air pollution on
      hip fracture incidence. This is the first study that shows these associations.

PMID- 30094609
TI  - Osteoporosis and osteopenia in the distal forearm predict all-cause mortality
      independent of grip strength: 22-year follow-up in the population-based Tromso
      Study.
AB  - : Low bone mineral density (BMD) gives an increased risk of fractures, which can
      lead to premature death. Can BMD of the wrist predict mortality? BMD consistent
      with osteopenia and osteoporosis gave a significantly increased risk of death for
      both men and women in a general population in Tromso, Norway. INTRODUCTION: To
      investigate if bone mineral density (BMD) levels of the distal forearm,
      consistent with osteopenia and osteoporosis, can predict mortality and if grip
      strength is an effect modifier. METHODS: The study population constituted 6565
      participants aged 50-79 years at baseline in the Tromso Study wave 4 conducted in
      1994-1995. Forearm BMD measured by SXA was categorized as "normal," "osteopenia,"
      or "osteoporosis" following WHO's definition. Cox regression with all-cause
      mortality as the outcome over 22 years of follow-up was performed for men and
      women separately, adjusting for health-related factors, as well as BMD by grip
      strength interaction. A secondary analysis with a 15-year follow-up also adjusted
      for hip fractures and osteoporotic fractures. RESULTS: During follow-up, 3176 of
      participants died (47%). Those categorized as osteoporotic had higher mortality
      hazard ratio (HR) compared to those with normal BMD; men HR = 1.37 (95%
      confidence interval (CI) 1.19, 1.58) and women HR = 1.32 (1.14, 1.53) were
      adjusted for age, body mass index, physical activity, smoking habits, education,
      health status, chronic diseases, and grip strength. Corresponding HRs for
      osteopenia were men HR = 1.13 (1.00, 1.27) and women HR = 1.17 (1.01, 1.35).
      Further adjustments for fractures did only marginally attenuate the results, and
      HRs were still significant. There was no grip strength by BMD interaction.
      CONCLUSION: Men and women with low distal forearm BMD values, consistent with
      osteoporosis or osteopenia, had an increased mortality compared to normal BMD
      participants. High grip strength did not modify this association, and the
      association remained after adjustment for a range of health-related factors.

PMID- 30094612
TI  - Eyelid injury after use of 3M DuraporeTM tape during general anesthesia.

PMID- 30094611
TI  - Development of the Utrecht Score for clavicle fractures: a short and complete
      clavicle score with patient-reported and objective measures.
AB  - PURPOSE: The purpose of this study was to develop a clavicle-specific
      questionnaire with patient-reported and objective measures. METHODS: The present
      study used data of DASH and Constant scores from a previously performed
      randomized-controlled trial comparing plate and intramedullary pin fixation of
      clavicle fractures. Exploratory factor analysis was used to identify the most
      relevant items and the underlying structure of the questionnaires. To optimize
      the applicability to patients with a clavicle fracture, the selected items were
      reformulated. If relevant themes were underexposed, an additional question was
      added. RESULTS: Based on the scree plot of eigenvalues and the parallel analysis,
      a seven-factor model with good factorability was constructed. Using exploratory
      factor analysis, 13 patient-reported and 2 objective measurements were
      identified. The internal consistency of the selected questions was excellent. An
      additional question was added to cover complaints relating to direct pressure on
      the clavicle and implants. CONCLUSION: The Utrecht Score for clavicle fractures
      is a compact yet complete tool that was developed to assess functional outcome
      specifically in patients with a clavicle fracture, consisting of patient-reported
      and objective measures. After external validation, the USC can be used for
      research purposes or clinical follow-up during rehabilitation in patients with a
      clavicle fracture.

PMID- 30094610
TI  - CXCL1 Derived from Mammary Fibroblasts Promotes Progression of Mammary Lesions to
      Invasive Carcinoma through CXCR2 Dependent Mechanisms.
AB  - With improved screening methods, the numbers of abnormal breast lesions diagnosed
      in women have been increasing over time. However, it remains unclear whether
      these breast lesions will develop into invasive cancers. To more effectively
      predict the outcome of breast lesions and determine a more appropriate course of
      treatment, it is important to understand the underlying mechanisms that regulate
      progression of non-invasive lesions to invasive breast cancers. A hallmark of
      invasive breast cancers is the accumulation of fibroblasts. Fibroblast
      proliferation and activation in the mammary gland is in part regulated by the
      Transforming Growth Factor beta1 pathway (TGF-beta). In animal models, TGF-beta
      suppression of CCL2 and CXCL1 chemokine expression is associated with metastatic
      progression of mammary carcinomas. Here, we show that transgenic overexpression
      of the Polyoma middle T viral antigen in the mouse mammary gland of C57BL/6 mice
      results in slow growing non-invasive lesions that progress to invasive carcinomas
      in a stage dependent manner. Invasive carcinomas are associated with accumulation
      of fibroblasts that show decreased TGF-beta expression and high levels of CXCL1,
      but not CCL2. Using co-transplant models, we show that decreased TGF-beta
      signaling in fibroblasts contribute to mammary carcinoma progression through
      enhancement of CXCL1/CXCR2 dependent mechanisms. Using cell culture models, we
      show that CXCL1 mediated mammary carcinoma cell invasion through NF-kappaB, AKT,
      Stat3 and p42/44MAPK dependent mechanisms. These studies provide novel
      mechanistic insight into the progression of pre-invasive lesions and identify new
      stromal biomarkers, with important prognostic implications.

PMID- 30094613
TI  - A cross-sectional study of the reporting quality of pilot or feasibility trials
      in high-impact anesthesia journals.
AB  - PURPOSE: Pilot trials inform the design and conduct of larger scale trials. Using
      the Consolidated Standards of Reporting Trials (CONSORT) pilot extension
      guidelines, we assessed reporting quality in five high-impact anesthesia journals
      and explored factors associated with reporting quality. METHODS: The five highest
      impact anesthesia journals were screened for randomized-controlled trials
      published as pilot or feasibility trials between 2006 and 2016. A pair of
      reviewers independently screened citations, extracted data, and assessed
      reporting quality using the CONSORT pilot trial extension checklists for
      abstracts and full texts. We reported the percentage adherence for each item,
      along with the median [interquartile range (IQR)] or mean (standard deviation
      [SD]) for all items. The factors considered to influence reporting were: 1) trial
      registration, 2) industry funding, 3) trial identification as a pilot or
      feasibility in the title or abstract, 4) primary objective as "feasibility", and
      5) the specific journal. The association was estimated using generalized
      estimating equations and reported as incidence rate ratios with 99% confidence
      intervals. RESULTS: Of 364 citations, 58 articles were eligible. The median [IQR]
      number of CONSORT abstract items reported was 5 [4-7], and the mean (SD) number
      of full text items reported was 13 (5). Significantly poor reporting was
      associated with "not registering the trial" (both abstracts and full texts),
      "trial not identified as a pilot" (abstracts), and "using clinical hypothesis as
      the primary objective" (full texts). CONCLUSION: The reporting quality of pilot
      trials published in leading anesthesia journals is poor. Journal editorial boards
      can encourage improved reporting by supporting adherence to the CONSORT extension
      for pilot trials.

PMID- 30094614
TI  - [Pulmonary fibrosis in rheumatic diseases].
AB  - Rheumatic diseases are frequently complicated by secondary pulmonary diseases,
      which often impair the quality of life and increase the mortality of patients. A
      correct classification of such pulmonary complications is important to ensure
      appropriate treatment and optimal prognosis. The diagnostic and therapeutic
      challenge is to find the precise diagnosis and appropriate therapy among the
      multitude of potential causes for respiratory symptoms. It is important to
      maintain a cautious approach to invasive diagnostics, even though the
      differential diagnostics of infections or toxic lung disease might be crucial.
      The situation is further complicated by the frequent lack of evidence for
      therapies. Especially in the case of pulmonary fibrosis which is comparable to
      cancer in its complexity and high mortality, the diagnostics and therapy should
      be discussed in appropriate interdisciplinary boards.

PMID- 30094615
TI  - Tissue Microbiome of Norway Spruce Affected by Heterobasidion-Induced Wood Decay.
AB  - Plants live in close association with microbial symbionts, which may affect the
      host fitness, productivity, and tolerance against biotic and abiotic stressors.
      The composition of plant microbial communities is influenced by many biotic and
      abiotic factors, but little is known about the effect of plant pathogens on the
      structure of these communities. In this study, we investigated the structure of
      bacterial communities associated with different tissues of asymptomatic and
      symptomatic (Heterobasidion-rotten) Norway spruce (Picea abies (L.) Karst.)
      trees. Our results demonstrated that each of the investigated anatomic tissues
      (root, bark, down stem, upper stem, and needles) harbored a unique bacterial
      assemblage. However, the health status of the host trees had little effect on the
      structure of bacterial communities, as the only significant differences among
      asymptomatic and symptomatic trees were found in the composition of the bacterial
      communities of needles. Proteobacteria was predominant in all anatomic regions
      with the highest abundance in needles (86.7%), whereas Actinobacteria showed an
      opposite trend, being more abundant in the woody tissues than in needles.
      Additionally, we performed profiling of terpenoid compounds present in spruce
      xylem and phloem. Total concentrations of monoterpenes and sesquiterpenes were
      considerably higher in asymptomatic trees. However, we found no significant
      correlations between terpenoid profiles of spruce trees and the composition of
      their bacterial communities. Our results provide an insight into the diversity of
      bacteria associated with Norway spruce tree tissues. At the same time, the health
      status and terpenoid content of host trees had a limited effect on the
      composition of bacterial communities in our survey.

PMID- 30094616
TI  - The Rosenzweig-MacArthur system via reduction of an individual based model.
AB  - The Rosenzweig-MacArthur system is a particular case of the Gause model, which is
      widely used to describe predator-prey systems. In the classical derivation, the
      interaction terms in the differential equation are essentially derived from
      considering handling time vs. search time, and moreover there exist derivations
      in the literature which are based on quasi-steady state assumptions. In the
      present paper we introduce a derivation of this model from first principles and
      singular perturbation reductions. We first establish a simple stochastic mass
      action model which leads to a three-dimensional ordinary differential equation,
      and systematically determine all possible singular perturbation reductions (in
      the sense of Tikhonov and Fenichel) to two-dimensional systems. Among the
      reductions obtained we find the Rosenzweig-MacArthur system for a certain choice
      of small parameters as well as an alternative to the Rosenzweig-MacArthur model,
      with density dependent death rates for predators. The arguments to obtain the
      reductions are intrinsically mathematical; no heuristics are employed.

PMID- 30094617
TI  - Prognostic significance of CEACAM5mRNA-positive circulating tumor cells in
      patients with metastatic colorectal cancer.
AB  - PURPOSE: Tauo evaluate the clinical relevance of CEACAM5mRNA-positive circulating
      tumor cells (CTCs) in patients with metastatic colorectal cancer (mCRC). METHODS:
      Peripheral blood was obtained from 436 patients with mCRC before the initiation
      of systemic therapy. A second sample was obtained on treatment assessment from
      296 (67.9%) patients. The detection of CEACAM5mRNA-positive CTCs was performed
      using a real-time PCR assay. RESULTS: The patients' median age was 67 years and
      PS (EGOG 0-1) 92%; KRAS exon 2 and BRAFV600E mutated primary tumors were
      identified in 31.9% and 6.4% of the tested patients, respectively, whereas
      metastasectomy was performed in 17.7% of the patients. Circulating CEACAM5mRNA
      positive CTCs were detected in 125 (28.7%) and 85 (28.7%) patients at baseline
      and on treatment assessment, respectively. The detection of CEACAM5mRNA-positive
      cells was revealed, in multivariate analysis, as an independent prognostic factor
      associated with decreased PFS (HR 1.6; 95% CI 1.1-2.5; p = 0.026) and OS (HR 2.2;
      95% CI 1.3-3.2; p < 0.001). The detection of CEACAM5mRNA-positive CTCs in
      patients with KRAS and BRAFV600E mutations was correlated with shorter PFS (p =
      0.041 and p = 0.022, respectively). Moreover, OS was significantly shorter in
      patients with CEACAM5+/KRAS mutations compared to those with CEACAM5+/KRAS wt
      tumors (p = 0.023). CONCLUSIONS: Detection of peripheral blood CEACAM5mRNA
      positive CTCs is an adverse prognostic factor correlated with poor clinical
      outcome in patients with mCRC, especially in patients with KRAS and BRAF mutated
      tumors.

PMID- 30094618
TI  - Correction to: DNA methylation-based reclassification of olfactory neuroblastoma.
AB  - In the original publication, the second name of the twentieth author was
      incorrect. It should read as 'Miguel Sainz-Jaspeado'. The original publication of
      the article has been updated to reflect the change. This correction was authored
      by Ulrich Schuller on behalf of all authors of the original publication.

PMID- 30094619
TI  - Correction to: Clopidogrel Pharmacogenetics in Iranian Patients Undergoing
      Percutaneous Coronary Intervention.
AB  - The original version of this article unfortunately contained a typo in the co
      author name.

PMID- 30094620
TI  - Influence of Obesity and Metabolic Abnormalities on the Risk of Developing
      Colorectal Neoplasia.
AB  - BACKGROUND: Obesity and metabolic syndrome are risk factors for colorectal
      neoplasia (CRN). However, the association between metabolically healthy obese
      (MHO) or metabolically unhealthy non-obese (MUNO) status and the risk of CRN
      remains unclear. AIMS: We aimed to elucidate the association between MHO or MUNO
      status and the risk of CRN. METHODS: A total of 139,023 asymptomatic subjects who
      underwent a primary screening colonoscopy were categorized into 4 groups
      according to obesity and metabolic status: metabolically healthy non-obese
      (MHNO), MHO, MUNO, and metabolically unhealthy obese (MUO). RESULTS: Mean
      participant age was 41.0 years, and the proportion of men was 65.3%. Among men,
      the risk of overall CRN increased in MHO (adjusted odds ratio [AOR] 1.22, 95%
      confidence intervals [CI] 1.12-1.33), MUNO (AOR 1.25, 95% CI 1.18-1.31), and MUO
      groups (AOR 1.47, 95% CI 1.40-1.54) compared with the MHNO group, whereas the
      risk of advanced CRN (ACRN) increased in MUNO (AOR 1.16, 95% CI 1.002-1.33) and
      MUO groups (AOR 1.49, 95% CI 1.31-1.70), but not in the MHO group (AOR 0.92, 95%
      CI 0.70-1.21). Moreover, among non-obese men, the risk of overall CRN and ACRN
      linearly increased with an increasing number of metabolic abnormalities. However,
      among women, only the MUO group had an increased risk of overall CRN (AOR 1.34,
      95% CI 1.21-1.47) and no other significant associations were observed.
      CONCLUSIONS: Poor metabolic health, regardless of obesity, is an independent risk
      factor for CRN in men. Our results suggest that men with metabolic abnormalities
      should be considered as a high-risk group for colorectal cancer, even if they are
      not obese.

PMID- 30094622
TI  - Influence of Ambulatory Triglyceride Levels on Risk of Recurrence in Patients
      with Hypertriglyceridemic Pancreatitis.
AB  - BACKGROUND AND AIMS: To evaluate impact of ambulatory triglyceride levels on risk
      of recurrent pancreatitis in patients with hypertriglyceridemic pancreatitis.
      METHODS: We conducted a longitudinal retrospective cohort study of patients with
      serum triglyceride level >= 500 mg/dL during index hospitalization for acute
      pancreatitis within a regional integrated healthcare system between 2006 and 2013
      (follow-up through 2015). Cases were identified based on combination of diagnosis
      codes and serum amylase/lipase. We used multivariable robust Poisson regression
      to determine independent effect of baseline (first outpatient) triglyceride
      measurement on risk of recurrent pancreatitis. Ambulatory triglyceride levels
      were categorized as normal (0-200 mg/dL), moderately elevated (201-500 mg/dL),
      and highly elevated (> 500 mg/dL). We further assessed factors related to
      likelihood of normalization of serum triglycerides (< 200 mg/dL) in the
      outpatient setting. RESULTS: One hundred and fifty-one patients met study
      inclusion criteria with median follow-up of 3 years. Overall, 45 (29.8%) patients
      experienced at least 1 recurrent attack with 25 (16.6%) experiencing multiple
      episodes. In multivariable analysis, patients that continued to have moderately
      elevated ((adjusted rate ratio RR 5.47 (95% CL 1.80, 16.65)) as well as highly
      elevated (RR 8.45 (2.55, 27.96)) triglycerides were at increased risk of disease
      recurrence compared to patients that achieved normalization. Patients with
      triglyceride measurement performed within 30 days from discharge were more likely
      to achieve normalization, 40 versus 26%, p = 0.03. CONCLUSIONS: For patients with
      hypertriglyceridemic pancreatitis, even modest elevation in subsequent
      triglyceride levels was associated with increased risk of recurrence. Future
      efforts should focus on ensuring timely care in the outpatient setting with a
      goal of normalizing triglycerides.

PMID- 30094621
TI  - Case-Control Study of Inflammatory Bowel Disease Patients with and without
      Clostridium difficile Infection and Poor Outcomes in Patients Coinfected with C.
      difficile and Cytomegalovirus.
AB  - BACKGROUND AND AIMS: Clostridium difficile infection (CDI) incidence and risk
      factors in patients with inflammatory bowel disease (IBD) have been extensively
      studied. However, data describing CDI in Chinese patients with IBD are limited.
      We investigated the cumulative incidence, risk factors, and outcomes of CDI in
      Chinese IBD patients. METHODS: We conducted a retrospective, case-control study
      of patients hospitalized with IBD and CDI at Peking Union Medical College
      Hospital from January 2010 to December 2015. CDI was diagnosed based on the
      presence of active symptoms and positive enzyme immunoassay-based stool test
      results for C. difficile toxin A or B (CDAB). Controls were selected from CDAB
      negative patients with IBD and matched by age, gender, phenotypes of IBD and the
      same time period of CDAB testing at a 1:2 or 1:3 ratio. RESULTS: We identified 60
      (7.41%) cases of CDI among 810 patients with IBD, and 137 control cases were
      selected. Univariate analysis revealed that IBD patients with CDI had higher
      rates of concurrent corticosteroid use, proton pump inhibitor, antibiotic use,
      recent hospitalization, parenteral nutrition support, and cytomegalovirus (CMV)
      coinfection (P < 0.05). Multivariate analysis revealed that concurrent
      corticosteroid use (odds ratio [OR] = 6.803, 95% confidence interval [CI] = 2.901
      15.954, P < 0.001) and hospitalization within 1 month (OR = 3.028, 95% CI = 1.225
      7.480, P = 0.016) were associated with CDI. CMV and C. difficile coinfection
      (hazard ratio [HR] = 4.185, 95% CI = 1.492-11.736, P = 0.007) as well as disease
      severity (HR 2.070, 95% CI = 1.006-4.261, P = 0.048) were independently
      associated with colectomy following CDI. CONCLUSIONS: IBD patients with
      concurrent corticosteroid use and recent hospitalization are at a higher risk of
      CDI. CMV and C. difficile coinfection is associated with poorer outcomes.

PMID- 30094623
TI  - Similar Sustained Virologic Response in Real-World and Clinical Trial Studies of
      Hepatitis C/Human Immunodeficiency Virus Coinfection.
AB  - BACKGROUND: Clinical trials evaluating efficacy of direct-acting antiviral (DAA)
      therapies demonstrate sustained virologic response (SVR) rates greater than 90%
      in patients infected with hepatitis C (HCV) and human immunodeficiency virus
      (HIV). However, generalizability of this data to real-world coinfected
      populations is unknown. AIM: We aim to compare efficacy data from clinical trials
      to effectiveness data of real-world observational studies that evaluate oral
      interferon-free HCV treatment regimens in patients infected with HIV and HCV.
      METHODS: We included English-language studies on PubMed and MEDLINE databases
      from inception until October 2017. Eight clinical trials and 11 observational
      studies reporting on efficacy data and effectiveness data, respectively, of
      interferon-free oral DAA regimens in HCV/HIV coinfected patients, were included.
      RESULTS: Of patients in the eight clinical trials evaluated, 93.1% (1218/1308)
      achieved SVR12; of the 11 real-world observational studies, 90.8% (2269/2499)
      achieved SVR12. Relative risk between those treated in clinical trials versus
      observational studies was 0.98. Patients with genotype 1 infection, African
      American patients, cirrhotic patients, and patients with prior HCV treatment
      experience had similar rates of SVR in real-world and clinical trial cohorts.
      CONCLUSION: SVR among real-world HCV/HIV coinfected populations treated with DAA
      regimens is similar to SVR of patients studied in clinical trials. Historically
      negative predictors of achieving SVR during the era of interferon-based
      treatments, such as those with cirrhosis, prior HCV treatment failure, GT1
      infection, and African-American race, are not associated with a significantly
      lower SVR in real-world populations treated with various DAA regimens.

PMID- 30094625
TI  - Plasma mtDNA Analysis Aids in Predicting Pancreatic Necrosis in Acute
      Pancreatitis Patients: A Pilot Study.
AB  - BACKGROUND: Specific plasma biomarkers in predicting pancreatic necrosis (PNec)
      are needed in treating acute pancreatitis (AP). AIMS: To investigate the
      prognostic value of plasma mitochondrial DNA fragments (mtDNA) in patient with AP
      for PNec. METHODS: AP patients with symptoms onset within 72 h were prospectively
      enrolled from June 2015 through June 2017 and were assessed for PNec using
      contrast-enhanced CT scan. Plasma mtDNA concentration (specific mitochondrial
      gene ND1) was measured using qRT-PCR. RESULTS: Of the 74 AP patients included,
      significant higher median level of plasma mtDNA was found in severe AP patients
      than in mild AP patients and healthy controls, but not in moderately severe AP
      patients. Patients with PNec had higher level of plasma mtDNA than those without
      PNec (774.2 [IQR 397.6-2205.0] vs. 169.5 [IQR 73.6-683.4] pg/ml, P < 0.05). The
      area under the receiver operator characteristic curve (ROC-AUC) of mtDNA for
      predicting PNec was higher than that of CRP (0.813 [95% CI 0.705-0.895] vs. 0.678
      [95% CI 0.558-0.783]). Using a cutoff value of 302.5 pg/ml, the sensitivity and
      specificity for diagnosing PNec were 90.9 and 68.3%, respectively. Finally,
      plasma mtDNA levels decreased significantly after continuous renal replacement
      therapy (717.7 [IQR 307.00-1370.00] vs. 237.5 [IQR 117.20-464.80] pg/ml, P <
      0.01). CONCLUSIONS: Elevated plasma mtDNA content in AP patients may be used as a
      more accurate early predictor of PNec in contrast to traditional CRP.

PMID- 30094627
TI  - Development and validation of a new score for measuring post-operative
      complications.
AB  - PURPOSE: Assigning a numerical value to post-operative morbidity may improve its
      usefulness as an outcome measure. The recently developed Comprehensive
      Complication Index (CCI) is a step forward in this process but assigns an
      inappropriately high score to a combination of complications. METHODS: We
      developed a new score called the complication severity score (CSS) using a
      mathematical process and compared it with the CCI using a questionnaire-based
      survey of 49 experienced gastrointestinal and hepato-pancreatico-biliary
      surgeons. The CSS was modified based on the results of this survey and was
      correlated with other patient-centered outcomes in a prospective cohort of
      consecutive patients undergoing elective surgery. RESULTS: Of the nine sets of
      scenarios, experienced surgeons' opinion matched with CSS in 6, CSS as well as
      CCI in 1, and neither CSS nor CCI in 2 scenarios. Of the total 441 responses, 281
      matched with CSS while 143 matched with CCI (p = 0.0001, odds ratio: 3.7; 95% CI:
      2.8 to 4.8). The modified CSS significantly correlated with the post-operative
      length of stay (r = 0.76; 95% CI: 0.68 to 0.82; p < 0.001), the length of ICU
      stay (r = 0.61; 95% CI: 0.50 to 0.70; p < 0.001) and with the difference between
      pre-operative and post-operative quality of life scores in the physical (r =
      0.29; 95% CI: 0.14 to 0.42; p < 0.001) and social (r = 0.29; 95% CI: 0.14 to
      0.43; p < 0.001) domains. CONCLUSIONS: The CSS more often matched the opinion of
      experienced senior surgeons compared to CCI. The modified CSS significantly
      correlated with other patient-centered outcomes.

PMID- 30094626
TI  - Optimal Omeprazole Dosing and Symptom Control: A Randomized Controlled Trial
      (OSCAR Trial).
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are potent inhibitors of acid secretion
      and are the mainstay of therapy for gastroesophageal reflux disease (GERD).
      Initially designed to be taken 30 min before the first daily meal, these agents
      are commonly used suboptimally, which adversely affects symptom relief. No study
      to date has assessed whether correcting dosing regimens would improve symptom
      control. The objective of this study was to determine whether patients with
      persistent GERD symptoms on suboptimal omeprazole dosing experience symptomatic
      improvement when randomized to commonly recommended dosing regimen and to
      evaluate the economic impact of suboptimal PPI dosing in GERD patients. METHODS:
      Patients with persistent heartburn symptoms >= 3 times per week treated with
      omeprazole 20 mg daily were enrolled and randomized to commonly recommended
      dosing or continued suboptimal dosing of omeprazole. The primary outcomes were
      changes in symptom, frequency, and severity, as determined using the
      Gastroesophageal Reflux Disease Symptom Assessment Scale (GSAS) 4 weeks after the
      intervention was administered. In secondary analysis, an alternative measure of
      symptom load was used to infer potential costs. RESULTS: Sixty-four patients were
      enrolled. GSAS symptom, frequency, and severity scores were significantly better
      when dosing was optimized for overall and heartburn-specific symptoms (P < 0.01
      for all parameters). Cost savings resulting from reduced medical care and
      workplace absenteeism were estimated to be $159.60 per treated patient, with cost
      savings potentially exceeding $4 billion annually in the USA. DISCUSSION: Low
      cost efforts to promote commonly recommended PPI dosing can dramatically reduce
      GERD symptoms and related economic costs. ClinicalTrials.gov, number:
      NCT02623816.

PMID- 30094624
TI  - Sleep Disturbances Are Commonly Reported Among Patients Presenting to a
      Gastroenterology Clinic.
AB  - BACKGROUND: Poor sleep quality is common among patients with gastrointestinal
      (GI) disorders. However, few studies have assessed the presence of insomnia or
      reported circadian preferences and none have directly compared sleep between
      common GI conditions. AIMS: To compare clinical sleep characteristics in patients
      presenting to a tertiary care GI clinic for irritable bowel syndrome (IBS),
      functional dyspepsia (FD), inflammatory bowel disease (IBD), gastroesophageal
      reflux disease (GERD), and celiac disease (CD). METHODS: Validated sleep measures
      were administered to consecutive patients if they were diagnosed with IBS, IBD in
      clinical remission, CD, FD, or GERD. Healthy Controls (HCs) with no reported GI
      diagnoses or symptoms were also recruited. RESULTS: A total of 212 eligible
      respondents completed this survey, 161 GI clinic patients (IBS (n = 48), GERD (n
      = 29), IBD in clinical remission (n = 44), CD (n = 40)), and 41 HCs. Only, 10
      respondents had a diagnosis of FD, and these were excluded. The IBS group had the
      highest frequency of poor sleep (72%) followed by CD (61%), GERD (60%), IBD
      (54%), and HC (39%). IBS patients also had the highest frequency of clinical
      insomnia (51%), followed by GERD (37%), CD (35%), IBD (27%), and HC (18%). 40% of
      IBS patients reported taking sleep medications at least once per week, compared
      to 32% of GERD, 23% IBD, 13% CD, and 15% HC. CONCLUSIONS: Patients presenting to
      a tertiary care GI clinic report poorer sleep than healthy controls. In general,
      patients with IBS report the highest rates of sleep difficulties compared to
      patients with other diagnoses.

PMID- 30094628
TI  - Hapke-based computational method to enable unmixing of hyperspectral data of
      common salts.
AB  - Environmental scientists are currently assessing the ability of hyper-spectral
      remote sensing to detect, identify, and analyze natural components, including
      minerals, rocks, vegetation and soil. This paper discusses the use of a nonlinear
      reflectance model to distinguish multicomponent particulate mixtures. Analysis of
      the data presented in this paper shows that, although the identity of the
      components can often be found from diagnostic wavelengths of absorption bands,
      the quantitative abundance determination requires knowledge of the complex
      refractive indices and average particle scattering albedo, phase function and
      size. The present study developed a method for spectrally unmixing halite and
      gypsum combinations. Using the known refractive indexes of the components, and
      with the assistance of Hapke theory and Legendre polynomials, the authors develop
      a method to find the component particle sizes and mixing coefficients for blends
      of halite and gypsum. Material factors in the method include phase function
      parameters, bidirectional reflectance, imaginary index, grain sizes, and
      iterative polynomial fitting. The obtained Hapke parameters from the best-fit
      approach were comparable to those reported in the literature. After the optical
      constants (n, the so-called real index of refraction and k, the coefficient of
      the imaginary index of refraction) are derived, and the geometric parameters are
      determined, single-scattering albedo (or omega) can be calculated and spectral
      unmixing becomes possible.

PMID- 30094629
TI  - Increased level of compleasomes in cerebrospinal fluid of patients with herpes
      simplex encephalitis.
AB  - Herpes simplex encephalitis (HSE) is a common cause of viral encephalitis (HSV-1)
      characterised by pronounced inflammation and elevated intracranial pressure. We
      have shown in a rat model that HSV-1 infection causes an interaction between
      complement factors and proteasomes, leading to formation of proteasome/complement
      complexes (compleasomes). Exposure of the proteasome regulatory subunit
      antisecretory factor 1 (AF1) leads to a decrease in intracranial pressure. The
      aim of this study was to evaluate the acute and prolonged formation of
      compleasomes in cerebrospinal fluid (CSF) from patients with HSE. Cerebrospinal
      fluid samples (n = 55) from 24 HSE patients were analysed for compleasome
      complexes. Samples from healthy controls (n = 23) and patient controls (n = 27)
      served as baseline information. Sandwich enzyme-linked immunosorbent assay
      (ELISA) for proteasomes and their complex formation with complement factor 3 or
      4, and Western blot for C3 activation were performed on CSF samples. Increased
      compleasome formation, both presenting as an initial formation and showing
      exposure of subunit AF1 in the compleasomes, was found in CSF samples drawn from
      patients with HSE compared with samples from the control groups (p < 0.0005). The
      total protein CSF concentration was equal in all groups. The levels were higher
      in the acute phase compared with late in the disease course (p < 0.0005).
      Complement 3 breakdown product iC3b was detected in CSF samples of the HSE
      patients. The early increased formation of compleasomes in CSF suggests that this
      complex may be involved in host defence against HSE.

PMID- 30094631
TI  - Both IRF3 and especially IRF7 play a key role to orchestrate an effective
      cerebral inflammatory response in a mouse model of herpes simplex virus
      encephalitis.
AB  - The impact of a deficiency in interferon regulatory factor (IRF)3 and IRF7 was
      evaluated in an herpes simplex virus encephalitis (HSE) model. Compared to wild
      type (WT), the mortality rates of infected IRF3-/- and IRF7-/- mice were higher
      and associated with increased brain viral titers. At a critical time post
      infection, IRF7-/- mice exhibited a deficit in IFN-beta production. At a later
      time point, levels of type I IFNs and cytokines were increased in brains of both
      deficient mice compared to WT. Our results suggest that IRF3, and especially
      IRF7, are important for an effective control of inflammatory responses during
      HSE.

PMID- 30094630
TI  - Alzheimer's disease neuropathology may not predict functional impairment in HIV:
      a report of two individuals.
AB  - With aging of HIV populations, there is concern that Alzheimer's disease (AD) may
      become prevalent and difficult to distinguish from HIV-associated neurocognitive
      disorders. To date, there are no reports documenting histologically verified
      Alzheimer's neuropathology in individuals with HIV and dementia. Herein, we
      report two antiretroviral-treated, virally suppressed, HIV-infected individuals
      autopsied by the Manhattan HIV Brain Bank. Subject A presented to study at 52
      years, already dependent in instrumental activities of daily living (ADLs), with
      severe cognitive impairment inclusive of learning and memory dysfunction. Her
      history was significant for educational disability and head trauma. She had rapid
      cognitive decline and, by death at age 59 years, was bed-bound, incontinent, and
      non-communicative. At autopsy, she exhibited severe AD neuropathologic change
      (NIA-AA score A3B3C3) and age-related tau astrogliopathy (ARTAG). She was
      homozygous for APOE epsilon3/epsilon3. No HIV DNA was detected in frontal lobe by
      nested polymerase chain reaction. Subject B was a community dwelling 81-year-old
      woman who experienced sudden death by pulmonary embolus. Prior to death, she was
      fully functional, living independently, and managing all ADLs. At autopsy, she
      displayed moderate amyloid and severe tau AD neuropathologic changes (A2B3C2),
      ARTAG, and cerebral congophilic angiopathy. She was an APOE epsilon3/epsilon4
      heterozygote, and HIV DNA, but not RNA, was detected in frontal lobe, despite 20
      years of therapy-induced viral suppression. We conclude that in the setting of
      HIV, AD neuropathology may occur with or without symptomatic cognitive
      dysfunction; as with seronegative individuals, there are likely to be complex
      factors in the generation of clinically relevant impairments.

PMID- 30094633
TI  - Does Distance Among Colonies and Resource Availability Explain the Intercolonial
      Aggressiveness in Nasutitermes aff. coxipoensis?
AB  - Aggressive behaviour can ensure animal access to local resources. To reduce
      constant costs in the defence of territories, species could save energy with
      conflicts avoiding aggression with neighbour or in situations with abundance of
      resources. In the present study, we analysed the effect of distance among
      colonies and resource availability on the aggression level and responses to
      chemical cues of Nasutitermes aff. coxipoensis (Holmgren) (Termitidae:
      Nasutitermitinae). Manipulation of resource offer was conducted in the field,
      where nests with different distances were kept without addition of baits
      (control), with addition of three or 16 sugarcane baits/nest. After 3 months,
      aggressiveness, linear and Y-shaped trail-following bioassays were carried out
      with all pairwise combinations of colonies in each treatment. Our results showed
      that aggressive index of N. aff. coxipoensis was affected by the resource
      availability. However, individuals from colonies with 0 and 3 baits/nest showed a
      higher number of fighting with neighbours than those from non-neighbours
      colonies. Termite workers from colonies without baits (control) followed shorter
      distance in the linear trails compared to those from colonies with addition of
      baits. In all treatments, there was no preference of workers in relation to the
      choice of chemical cues from own or other colonies. The response of intercolonial
      aggressiveness in N. aff. coxipoensis seems to be resource-dependent. These
      results may contribute to the comprehension of the use of space by N. aff.
      coxipoensis and could be useful to explain patterns of termite co-occurrence at
      different spatial scales, from local (inside the nest-e.g. cohabitation of nests
      by inquilines) to regional (e.g. around the nest).

PMID- 30094634
TI  - Additive or synergistic? Early ectomycorrhizal fungal community response to mixed
      tree plantings in boreal forest reclamation.
AB  - Ectomycorrhizal fungi are an important component to ecosystem function in the
      boreal forest. Underlying factors influencing fungal community composition and
      richness, such as host identity and soil type have been studied, but interactions
      between these factors have been less explored. Furthermore, mixed-species stands
      may have additive or synergistic effects on ectomycorrhizal fungi species
      richness, but this effect is challenging to test on natural sites due to
      difficulty in finding monospecific and mixed-species stands with similar site
      conditions and history. Forest reclamation areas can provide an opportunity to
      explore some of these fundamental questions, as site conditions and history are
      often known and managed, with the added benefit that knowledge emerging from
      these studies can be used to evaluate the recovery of degraded forest landscapes.
      Here, we compared the richness and composition of ectomycorrhizal fungi in young
      single- and mixed-species stands established on a reclamation area designed to
      inform strategies to restore upland boreal forests disturbed by oil sands mining.
      Seedlings of three host tree species (Populus tremuloides, Pinus banksiana, Picea
      glauca) were planted in single- and mixed-species stands on three different
      salvaged soils (forest floor material, peat, subsoil). After four growing
      seasons, there was no difference in total ectomycorrhizal fungi species richness
      and composition in mixed- versus combined single-species stands indicating that
      an additive effect of host tree species prevailed early in development. However,
      there were compositional shifts in fungal communities across both the host tree
      species and the salvaged soil type, with soil type being the strongest driver.

PMID- 30094632
TI  - A NEET distinction: youths not in employment, education or training follow
      different pathways to illness and care in psychosis.
AB  - PURPOSE: The early phases of psychosis, including the prodrome, often feature
      educational/occupational difficulties and various symptoms and signs, that can
      render or keep youths "Not in Employment, Education or Training" (NEET).
      Conversely, NEET status itself may increase risk for illness progression and
      impaired functioning, and impede access to appropriate services for psychosis. As
      these issues have not been investigated, we aimed to examine differences in the
      illness and care pathways and characteristics of youths with psychosis who are
      NEET and non-NEET. METHODS: Youths entering a catchment-based Canadian early
      intervention service for psychosis (N = 416) were assessed as being NEET or non
      NEET and compared on symptomatology, premorbid adjustment, prodrome and duration
      of untreated psychosis (DUP). RESULTS: Thirty-nine percent of the sample was
      NEET. Compared to non-NEET youths, NEET youths had 34% higher negative symptoms
      scores, longer prodromes (median of 52 weeks vs. 24 weeks), and were more often
      continuously ill after their first psychiatric change until the onset of
      psychosis (62% vs. 45%). Both groups had similar premorbid adjustment scores
      until late adolescence when scores were significantly worse for NEET youths.
      Accounting for other predictors, NEET youths had 23% longer DUPs on average,
      despite having made more help-seeking attempts. CONCLUSIONS: Despite being more
      narrowly defined, NEET status was thrice as prevalent in our sample as in the
      Canadian population. The NEET group followed a distinct trajectory of persistent
      symptoms and functional decline before presenting with a psychotic disorder. The
      systemic delays that NEET youths encountered indicate a need for better-targeted
      early identification efforts.

PMID- 30094636
TI  - Using local softness to reveal oxygen participation in redox processes in cathode
      materials.
AB  - In this paper, the use of chemical local softness s(r) is proposed as an
      alternative way of analyzing the initial redox processes that occur in cathode
      materials used for lithium-ion batteries. It is shown that the chemical local
      softness is a quantity able to capture the same effects as the standard analysis
      based on the projected density of states. Because of its own nature, the local
      softness reveals the atomic sites involved in charge-transfer events and allows a
      quantitative comparative analysis between different materials. As pointed out by
      Johannes et al. (Solid State Ion 286:83-89, 2016), this analysis can be used as
      an indicator of stability of cathode materials for Li-ion batteries.

PMID- 30094637
TI  - Assessment of the Correlation Between Preoperative and Immediate Postoperative
      Gastric Volume and Weight Loss After Sleeve Gastrectomy Using Computed Tomography
      Volumetry.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has achieved excellent results
      in treatment of morbid obesity. The present study aimed to evaluate the impact of
      the preoperative gastric volume, volume of the remaining gastric pouch, and
      volume of the resected stomach on weight loss after LSG. METHODS: Patients with
      morbid obesity who underwent LSG were investigated by CT volumetry before and 1
      week after LSG to measure the volume of the stomach before and after the
      procedure, and the volume of the resected stomach was also calculated. The
      percentage of excess weight loss (EWL) and decrease in body mass index (BMI) at 6
      months postoperatively were measured and correlated with preoperative and
      postoperative gastric volumes. RESULTS: Forty-seven patients (44 females) were
      included to the study. A significant decrease in the gastric volume and BMI after
      LSG was noted. Preoperative gastric volume was positively correlated with
      preoperative BMI (r = 0.723, p < 0.00001) but not correlated with %EWL at 6
      months. The volume of the remaining gastric pouch was positively correlated with
      BMI at 6 months postoperatively (r = 0.597, p < 0.00001) and negatively
      correlated with %EWL (r = -0.7495, p < 0.00001). The correlation between the size
      of resected stomach and %EWL was statistically insignificant, yet the mean
      percentage of the resected stomach was directly correlated to %EWL. CONCLUSION:
      The preoperative volume of the stomach was positively correlated with baseline
      BMI, but not correlated with %EWL. The size of the remaining gastric pouch and
      the percentage of the resected stomach had significant impact on %EWL after LSG.

PMID- 30094635
TI  - Solar and terrestrial radiations explain continental-scale variation in bird
      pigmentation.
AB  - Animals living on the earth's surface are protected from the damaging effects of
      solar ultraviolet (UV) radiation by melanin pigments that color their integument.
      UV levels that reach the earth's surface vary spatially, but the role of UV
      exposure in shaping clinal variations in animal pigmentation has never been
      tested. Here, we show at a continental scale in Europe that golden eagles Aquila
      chrysaetos reared in territories with a high solar UV-B radiation exposure
      deposit lower amounts of the sulphurated form of melanin (pheomelanin) in
      feathers and consequently develop darker plumage phenotypes than eagles from
      territories with lower radiation exposure. This clinal variation in pigmentation
      is also explained by terrestrial gamma radiation levels in the rearing
      territories by a similar effect on the pheomelanin content of feathers, unveiling
      natural radioactivity as a previously unsuspected factor shaping animal
      pigmentation. These findings show for the first time the potential of solar and
      terrestrial radiations to explain pigmentation phenotype diversity in animals,
      including humans, at large spatial scales.

PMID- 30094638
TI  - The Cost of Intramedullary Nailing Versus Skeletal Traction for Treatment of
      Femoral Shaft Fractures in Malawi: A Prospective Economic Analysis.
AB  - BACKGROUND: In many low- and middle-income countries, non-surgical management of
      femoral shaft fractures using skeletal traction is common because intramedullary
      (IM) nailing is perceived to be expensive. This study assessed the cost of IM
      nailing and skeletal traction for treatment of femoral shaft fractures in Malawi.
      METHODS: We used micro-costing methods to quantify the costs associated with IM
      nailing and skeletal traction. Adult patients who sustained an isolated closed
      femur shaft fracture and managed at Queen Elizabeth Central Hospital in Malawi
      were followed from admission to discharge. Resource utilization and time data
      were collected through direct observation. Costs were quantified for procedures
      and ward personnel, medications, investigations, surgical implants, disposable
      supplies, procedures instruments and overhead. RESULTS: We followed 38 nailing
      and 27 traction patients admitted between April 2016 and November 2017. Nailing
      patient's average length of stay (LOS) was 36.35 days (SD 21.19), compared to 61
      (SD 18.16) for traction (p = 0.0003). The total cost per patient was $596.97
      ($168.81) for nailing and $678.02 (SD $144.25) for traction (p = 0.02). Major
      cost drivers were ward personnel and overhead; both are directly proportional to
      LOS. Converting patients from traction to nailing is cost-saving up to day 23
      post-admission. CONCLUSION: Savings from IM nailing as compared with skeletal
      traction were achieved by shortened LOS. Although this study did not assess the
      effectiveness of either intervention, the literature suggests that traction
      carries a higher rate of complications than nailing. Investment in IM nailing
      capacity may yield substantial net savings to health systems, as well as improved
      clinical outcomes.

PMID- 30094639
TI  - Enhanced Recovery in Liver Transplantation: A Feasibility Study.
AB  - BACKGROUND: Enhanced Recovery After Surgery (ERAS) programmes after surgery are
      effective in reducing length of stay, functional recovery and complication rates
      in liver surgery (LS) with the indirect advantage of reducing hospitalisation
      costs. Preoperative comorbidities, challenging surgical procedures and complex
      post-operative management are the points that liver transplantation (LT) shares
      with LS. Nevertheless, there is little evidence regarding the feasibility and
      safety of ERAS programmes in LT. METHODS: We designed a pilot, small-scale,
      feasibility study to assess the impact on hospital stay, protocol compliance and
      safety of an ERAS programme tailored for LT. The ERAS arm was compared with a 1:2
      match paired control arm with similar characteristics. All patients with MELD <25
      were included. A dedicated LT-tailored protocol was derived from publications on
      ERAS liver surgery. RESULTS: Ten patients were included in the Fast-Trans arm. It
      was observed a 47% reduction of the total LOS, as compared to the control arm:
      9.5 (9.0-10.5) days versus 18.0 (14.3-24.3) days, respectively, p <0.001. The
      protocol achieved 72.9% compliance. No differences were observed in terms of post
      operative complications or readmission rates after discharge between the two
      arms. Overall, it was observed a reduction of length of stay in ICU and surgical
      ward in the Fast-Trans arm compared with the control arm. CONCLUSION: Considered
      the main points in common between LS and LT, this small-scale study suggests that
      the application of an ERAS programme tailored to the LT setting is feasible.
      Further testing will be appropriate to generalise these findings.

PMID- 30094641
TI  - CD8+ iT cell, a budding star for cancer immunotherapy.

PMID- 30094640
TI  - Glioblastoma radiomics: can genomic and molecular characteristics correlate with
      imaging response patterns?
AB  - PURPOSE: For glioblastoma (GBM), imaging response (IR) or pseudoprogression (PSP)
      is frequently observed after chemoradiation and may connote a favorable
      prognosis. With tumors categorized by the Cancer Genome Atlas Project
      (mesenchymal, classical, neural, and proneural) and by methylguanine
      methyltransferase (MGMT) methylation status, we attempted to determine if certain
      genomic or molecular subtypes of GBM were specifically associated with IR or PSP.
      METHODS: Patients with GBM treated at two institutions were reviewed. Kaplan
      Meier method was used to estimate overall survival (OS) and progression-free
      survival (PFS). Mantel-cox test determined effect of IR and PSP on OS and PFS.
      Fisher's exact test was utilized to correlate IR and PSP with genomic subtypes
      and MGMT status. RESULTS: Eighty-two patients with GBM were reviewed. The median
      OS and PFS were 17.9 months and 8.9 months. IR was observed in 28 (40%) and was
      associated with improved OS (median 29.4 vs 14.5 months p < 0.01) and PFS (median
      17.7 vs 5.5 months, p < 0.01). PSP was observed in 14 (19.2%) and trended towards
      improved PFS (15.0 vs 7.7 months p = 0.08). Tumors with a proneural component had
      a higher rate of IR compared to those without a proneural component (IR 60% vs
      28%; p = 0.03). MGMT methylation was associated with IR (58% vs 24%, p = 0.032),
      but not PSP (34%, p = 0.10). CONCLUSION: IR is associated with improved OS and
      PFS. The proneural subtype and MGMT methylated tumors had higher rates of IR.

PMID- 30094642
TI  - TAVR Vs. SAVR in Intermediate-Risk Patients: What Influences Our Choice of
      Therapy.
AB  - PURPOSE OF REVIEW: To determine what influences patients and physicians to choose
      between transcatheter aortic valve replacement (TAVR) or surgical aortic valve
      replacement (SAVR) in intermediate-surgical-risk patients with severe,
      symptomatic aortic stenosis. RECENT FINDINGS: Advances in transcatheter valve
      technology, techniques, and trials demonstrating non-inferiority compared to
      surgical aortic valve replacement (SAVR) have led to expanded eligibility of
      transcatheter aortic valve replacement (TAVR) to both intermediate-risk patients
      in clinical practice and low-risk patients in pivotal trials. Since lower-risk
      individuals tend to be younger and good operative candidates, concerns of valve
      durability, procedure-related morbidity, and patient survivability require
      careful consideration. Results from the PARTNER II intermediate risk trials and
      SURTAVI trials have given us insight into the benefits and potential risks of
      both treatment modalities. In this article, we review the brief yet remarkable
      history of TAVR and discuss its role in the treatment of intermediate-surgical
      risk patients.

PMID- 30094644
TI  - A simple prognostic index for Shigatoxin-related hemolytic uremic syndrome at
      onset: data from the ItalKid-HUS network.
AB  - Shigatoxin Escherichia coli-related hemolytic uremic syndrome (eHUS) is a severe
      thrombotic microangiopathy (TMA) burdened by life-threatening complications and
      long-term sequelae. Since hemoconcentration is associated with worse outcome, we
      tried to develop a reliable and easy-to-calculate index for predicting
      complications and sequelae based on hemoglobin (Hb) at presentation. The first
      laboratory examinations with signs of TMA in eHUS patients were analyzed in
      relation to the outcomes with the receiver operating characteristic curves and
      their areas under the curve (AUC) for Hb and creatinine (sCr). A total of 197
      eHUS patients were identified of whom 24% did not have anemia at presentation. Hb
      level was the best predictor of a poor outcome (AUC 0.67) but the combination of
      Hb with sCr, in the formula [(Hb in g/dL + (sCr in mg/dL * 2)], showed an even
      better AUC of 0.75. The described scoring system was also strongly associated and
      predictive of all complications and health care needs (8% of patients with
      scoring > 13 died or entered a permanent vegetative state compared with 0% of
      those with <= 13).Conclusion: The presented score is a simple and early predictor
      of both short- and long-term outcomes and identifies patients who should undergo
      rapid volume expansion to counteract hemoconcentration, the spreading of
      microvascular thrombosis, and the consequent increased organ damage. What is
      Known: * In eHUS, hemoconcentration is associated with worse short- and long-term
      outcome. * A prognostic index to identify patients at higher risk for
      complications at presentation is not available. What is New: * We developed a
      simple and early prognostic index for eHUS outcome with the combination of Hb and
      sCr at onset, in the following formula [(Hb in g/dL + (sCr in mg/dL * 2)]. * The
      proposed HUS Severity Score can promptly identify patients with good outcome and
      those with high risk of worse short- and long-term outcome.

PMID- 30094643
TI  - Enhanced biosynthesis of phenazine-1-carboxamide by Pseudomonas chlororaphis
      strains using statistical experimental designs.
AB  - Phenazine-1-carboxamide (PCN) is one of the major biocontrol agents produced by
      plant growth-promoting rhizosphere (PGPR) pseudomonads including Pseudomonas
      chlororaphis. In this study, a combined strategy of genetic modification and
      statistical experimental designs was applied to obtain mutants of P. chlororaphis
      strains with high-yield PCN production. To achieve this, the lon gene was knocked
      out in wild-type P. chlororaphis HT66 and the breeding mutant P3 strain with a
      non-scar deletion strategy. The resulting HT66Deltalon and P3Deltalon mutants
      produced a significantly higher PCN production in shake-flask cultures which was
      5- and  9-folds greater than their native counterparts. The potential ability of
      strain P3Deltalon for PCN production was further optimized by statistical
      designs. A two-level Plackett-Burman (PB) experimental design with six variables
      was employed to scrutinize medium components that significantly influence PCN
      production. Notably, glycerol, tryptone, and soy peptone were identified to be
      the most significant factors (p < 0.05). Response surface methodology (RSM) based
      on the central composite design (CCD) was adopted to determine these factors
      optimal levels and their interactive effects between culture components for PCN
      production. The predicted maximum PCN production was 9002 mg/L, whereas an actual
      PCN production of 9174 mg/L was recorded in the validation experiments using the
      optimal medium containing glycerol 37.08 mL/L, tryptone 20.00 g/L, and soy
      peptone 25.03 g/L, which was nearly threefolds higher than without optimization
      and 20-folds higher than the wild-type strain. In conclusion, the results
      revealed that P. chlororaphis display a high potential for industrial-scale
      production for phenazine biopesticides.

PMID- 30094646
TI  - Significant metabolic improvement by a water extract of olives: animal and human
      evidence.
AB  - PURPOSE: Dyslipidemia and impaired glucose metabolism are the main health issues
      of growing prevalence and significant high healthcare cost, requiring novel
      prevention and/or therapeutic approaches. Epidemiological and animal studies
      revealed that olive oil is an important dietary constituent, inducing
      normolipidemia. However, no studies have specifically investigated the polyphenol
      rich water extract of olives (OLWPE), generated during olive oil production.
      METHODS: In the present work, we initially examined the effect of OLPWE on
      animals' metabolic parameters. Rats fed with a high-fat diet were treated with
      three different doses of OLPWE for 4 months. Additionally, bioavailability was
      explored. Afterwards, OLWPE's metabolic effect was explored in humans. Healthy
      volunteers consumed microencapsulated OLWPE for 4 weeks, in a food matrix [one
      portion (30 g) of a meat product]. RESULTS: High-fat-fed rats developed a
      metabolic dysfunction, with increased LDL and insulin levels and decreased HDL;
      this syndrome was significantly impaired when treated with OLWPE. Treated rats
      had increased total plasma antioxidant capacity, while several phenolic compounds
      were detected in their blood. These findings were also verified in humans that
      consumed OLWPE, daily, for 4 weeks. Interestingly, in individuals with elements
      of cardio-metabolic risk, OLWPE consumption resulted in reduced glucose, insulin,
      total cholesterol, LDL and oxLDL levels. CONCLUSIONS: Our data clearly show that
      OLWPE can improve glucose and lipid profile, indicating its possible use in the
      design of functional food and/or therapeutic interventions.

PMID- 30094647
TI  - [Total hip replacement in avascular femoral head necrosis].
AB  - BACKGROUND: Avascular necrosis of the femoral head is a progressive perfusion
      disorder of the hip joint. Progress in avascular necrosis causes structural
      damage to the affected joint, often requiring total hip replacement. AIM: This
      article is intended to give the reader an overview of the current literature on
      total hip replacement of patients with an avascular necrosis of the femoral head.
      RESULTS: Before 1990, patients with avascular necrosis of the femoral head had
      significantly higher revision rates after total hip replacement. Recent studies,
      however, showed no significant differences in clinical outcomes after total hip
      replacement in femoral head necrosis and primary osteoarthritis. Despite the
      young age of the patients, good long-term clinical results can be expected even
      in patients with an avascular necrosis of the femoral head after total hip
      replacement.

PMID- 30094645
TI  - Prenatal Stress, Maternal Immune Dysregulation, and Their Association With Autism
      Spectrum Disorders.
AB  - PURPOSE OF REVIEW: While genetic factors are a major etiological contributor to
      autism spectrum disorder (ASD), evidence also supports a role for environmental
      factors. Herein, we will discuss two such factors that have been associated with
      a significant proportion of ASD risk: prenatal stress exposure and maternal
      immune dysregulation, and how sex and gender relate to these factors. RECENT
      FINDINGS: Recent evidence suggests that maternal stress susceptibility interacts
      with prenatal stress exposure to affect offspring neurodevelopment. Additionally,
      understanding of the impact of maternal immune dysfunction on ASD has recently
      been advanced by recognition of specific fetal brain proteins targeted by
      maternal autoantibodies, and identification of unique mid-gestational maternal
      immune profiles. Animal models have been developed to explore pathophysiology
      targeting both of these factors, with limited sex-specific effects observed.
      While prenatal stress and maternal immune dysregulation are associated with ASD,
      most cases of these prenatal exposures do not result in ASD, suggesting
      interaction with multiple other risks. We are beginning to understand the
      behavioral, pharmacopathological, and epigenetic effects related to these
      interactions, as well as potential mitigating factors. Sex differences of these
      risks have been understudied but are crucial for understanding the higher
      prevalence of ASD in boys. Continued growth in understanding of these mechanisms
      may ultimately allow for the identification of multiple potential points for
      prevention or intervention, and for a personalized medicine approach for this
      subset of environmental-associated ASD cases.

PMID- 30094649
TI  - Evaluation of a new tricalcium phosphate for guided bone regeneration: an
      experimental study in the beagle dog.
AB  - This study compared the in vivo behavior of two biomaterials, xenograft (Bio
      Oss(r)) and alloplastic tricalcium phosphate (Sil-Oss(r)), vs a control (no
      biomaterial) in beagle dogs treated with guided bone regeneration (GBR). Six male
      adult beagle dogs were included. The third and fourth mandibular premolars and
      first mandibular molars (3P3, 4P4 and 1M1) on both sides were extracted. After 12
      weeks of healing, Straumann implants (3.3 * 8 mm) were placed, performing
      standardized defects (3.3 * 6 mm) in the vestibular aspect of the alveolar bone.
      The defects were surgically treated by randomized placement of xenograft (Bio
      Oss(r)), alloplastic tricalcium phosphate (Sil-Oss(r)) or no biomaterial and
      covered with a resorbable collagen membrane (BioGide(r)). After an additional 12
      week healing period, the lower jaws were dissected. Total area regenerated in the
      region of interest, total volume, bone to implant contact in the regenerated
      area, and volumetric changes were measured through histological,
      histomorphometrical and microcomputed tomography (microCT) techniques. The
      negative control group showed bone ingrowth inside the defect, with a partial
      collapse of the buccal bone. This was not observed in the biomaterial-treated
      groups. Defects treated with the xenograft showed 51.40% (SD 19.83) newly
      mineralized tissue, while those treated with alloplastic tricalcium showed 62.54%
      (SD 11.54) newly mineralized tissue; the control showed 71.52% (SD 6.46).
      Alloplastic tricalcium phosphate modified with monetite and zinc showed similar
      features in alveolar regeneration of defects to those treated with the xenograft
      or conventional GBR, but it showed an ideally higher rate of new mineralized
      tissue formation and accelerated resorption.

PMID- 30094648
TI  - Swimming versus running: effects on exhaled breath condensate pro-oxidants and
      pH.
AB  - PURPOSE: The respiratory redox-state of swimmers can be affected by chronic
      exposures to chlorinated pools, and the effects of different exercises on it are
      unknown. Our aim was to compare two exercises performed at high-intensity and
      under habitual environmental conditions (swimming indoor vs. running outdoor) on
      the production of pro-oxidants (hydrogen peroxide and nitrite) and pH in exhaled
      breath condensate (EBC) and spirometry parameters in competitive swimmers
      chronically exposed to chlorinated pools. METHODS: Seventeen men and women (mean
      age +/- SD = 21 +/- 2 years) swam 3.5 km in an indoor pool treated with Cl2, and
      after 2-weeks, they ran 10 km outdoors. The pHEBC, [H2O2]EBC, [NO2-]EBC, [NO2
      ]EBC/[NO2-]Plasma and spirometry parameters were analyzed pre-exercise and 20 min
      and 24 h after exercise ended. RESULTS: Two mixed models were applied to compare
      EBC parameters between swimming and running. Lower levels of [H2O2]EBC and [NO2
      ]EBC (p = 0.008 and p = 0.018, respectively) were found 24-h post-swimming, and
      the same trend was observed for [NO2-]EBC/[NO2-]Plasma (p = 0.062). Correlations
      were found in both exercises between pre-exercise levels of pHEBC, [H2O2]EBC,
      [NO2-]EBC, and [NO2-]EBC/[NO2-]Plasma and their changes (Delta) after 24-h as
      well as between [H2O2]EBC and [NO2-]EBC for basal levels and for changes after 24
      h. A relationship was also found for running exercise between pulmonary
      ventilation and changes after 24 h in [H2O2]EBC. Spirometry data were unaffected
      in both types of exercise. CONCLUSION: In competitive swimmers, at 24-h acute
      post-exercise follow-up, swimming decreased and running increased pro-oxidant
      biomarkers of pulmonary origin, without changes in lung function.

PMID- 30094650
TI  - Effect of self-etch adhesives on the internal adaptation of composite
      restoration: a CP-OCT Study.
AB  - Despite improvements in dental adhesive materials, internal adaptation remains a
      challenge in bonded restorations. The aim of this study was to compare microgaps
      and internal floor adaptation between two different self-etch adhesives in class
      V cavities using cross-polarization optical coherence tomography (CP-OCT). In
      this in vitro study, standardized round class-V cavities were prepared in 20 non
      carious human upper central incisor teeth. They were randomly divided into two
      groups, TN and SE, with each group receiving a different dental adhesive. In TN
      group, the adhesive used was all-in-one Tetric N-Bond Self-Etch (TN;
      Ivoclar/Vivadent, Liechtenstein), while SE group was bonded with two-step self
      etch Clearfil SE Bond 2 adhesive (SE; Kuraray Noritake Dental Inc, Japan). The
      prepared cavities were restored with flowable composite and then stored in
      distilled water for 24 h. Next, they were immersed in silver nitrate, followed by
      immersion in a photo-developing solution. Optical comparison was carried out by
      CP-OCT to assess microgaps and composite adaptation at the cavity floor. A Mann
      Whitney test was applied to the data, which showed a statistically significant
      difference in composite adaptation among the two groups (p < 0.001) with the SE
      group showing superior adaptation. CP-OCT is a reliable tool for non-invasive
      imaging that gives an insight into composite performance. Better adaptation was
      found with the two-step self-adhesive for the composite used in this study.

PMID- 30094651
TI  - Multi-Modality Imaging in the Evaluation and Treatment of Tricuspid
      Regurgitation.
AB  - PURPOSE OF REVIEW: The goal of this review is to cover the epidemiology of
      tricuspid regurgitation (TR), anatomy of the tricuspid valve (TV), and the
      mechanisms and modern treatment of TR. The focus will be on the role of
      echocardiography, cardiac CT, and MRI to determine the mechanism, severity, and
      management strategies of TR. RECENT FINDINGS: The evaluation and management of TR
      is a rapidly growing field with significant advances in both imaging and
      interventions. Important advances have been made to understand TV anatomy and
      physiology in 3D echo, CT, and MRI. Additional understanding of the abnormal
      outcomes in both primary TR and secondary TR have been appreciated. Multiple
      transcatheter devices have reached the stage of early trials in high surgical
      risk cohorts with favorable initial findings. TR is a significant cardiovascular
      problem and vastly undertreated in the present era. There has been tremendous
      growth in knowledge of mechanisms of TR, its prognostic implications, timing of
      intervention, and development of novel treatment strategies. Multimodality
      imaging plays a key role in evaluation and treatment of this condition.

PMID- 30094653
TI  - Sparse Detector Configuration in SiPM Digital Photon Counting PET: a Feasibility
      Study.
AB  - PURPOSE: To investigate the minimum number of SiPM detectors required for solid
      state digital photon counting (DPC) oncologic whole-body 2-deoxy-2-[18F]fluoro-D
      glucose ([18F]FDG) positron emission tomography (PET)/X-ray computed tomography
      (CT). PROCEDURES: A DPC PET/CT (Vereos, Philips) with 23,040 1-to-1 crystal-to
      detector couplings was utilized. [18F]FDG PET/CT of a uniformity phantom and 10
      oncology patients selected by block randomization from a large clinical trial
      were included (457 +/- 38 MBq, 64 +/- 22 min p.i, body mass index (BMI) of 14
      41). Sparse-ring PET configurations with 50 % detector reduction in tangential
      and axial directions were analyzed and compared to the current full ring
      configuration. Resulting images were reviewed blindly and quantitatively over
      detectable lesions and the liver. RESULTS: One hundred twelve lesions (d = 10 to
      95 mm) were analyzed in the patient population. All lesions remained visible and
      were demonstrated without compromised image quality under all BMIs in the 50 %
      sparse detector configurations despite the DPC PET system sensitivity reduction
      to 1/4th. An excellent consistency of SUVmax measurements of lesions with an
      average of 5 % SUVmax difference was found between dPET of full and sparse
      configurations. CONCLUSIONS: The feasibility of either expanding the axial field
      of view (FOV) by a factor of two or halving the number of detectors was
      demonstrated for solid-state digital photon counting PET, thus either potentially
      enabling cost reduction or extended effective axial FOV without increased cost.

PMID- 30094656
TI  - A versatile hybrid agent-based, particle and partial differential equations
      method to analyze vascular adaptation.
AB  - Peripheral arterial occlusive disease is a chronic pathology affecting at least 8
      12 million people in the USA, typically treated with a vein graft bypass or
      through the deployment of a stent in order to restore the physiological
      circulation. Failure of peripheral endovascular interventions occurs at the
      intersection of vascular biology, biomechanics, and clinical decision making. It
      is our hypothesis that the majority of endovascular treatment approaches share
      the same driving mechanisms and that a deep understanding of the adaptation
      process is pivotal in order to improve the current outcome of the procedure. The
      postsurgical adaptation of vein graft bypasses offers the perfect example of how
      the balance between intimal hyperplasia and wall remodeling determines the
      failure or the success of the intervention. Accordingly, this work presents a
      versatile computational model able to capture the feedback loop that describes
      the interaction between events at cellular/tissue level and mechano-environmental
      conditions. The work here presented is a generalization and an improvement of a
      previous work by our group of investigators, where an agent-based model uses a
      cellular automata principle on a fixed hexagonal grid to reproduce the leading
      events of the graft's restenosis. The new hybrid model here presented allows a
      more realistic simulation both of the biological laws that drive the cellular
      behavior and of the active role of the membranes that separate the various layers
      of the vein. The novel feature is to use an immersed boundary implementation of a
      highly viscous flow to represent SMC motility and matrix reorganization in
      response to graft adaptation. Our implementation is modular, and this makes us
      able to choose the right compromise between closeness to the physiological
      reality and complexity of the model. The focus of this paper is to offer a new
      modular implementation that combines the best features of an agent-based model,
      continuum mechanics, and particle-tracking methods to cope with the multiscale
      nature of the adaptation phenomena. This hybrid method allows us to quickly test
      various hypotheses with a particular attention to cellular motility, a process
      that we demonstrated should be driven by mechanical homeostasis in order to
      maintain the right balance between cells and extracellular matrix in order to
      reproduce a distribution similar to histological experimental data from vein
      grafts.

PMID- 30094655
TI  - Dual-aptamer based electrochemical sandwich biosensor for MCF-7 human breast
      cancer cells using silver nanoparticle labels and a poly(glutamic acid)/MWNT
      nanocomposite.
AB  - This paper reports on a sensitive and selective method for the detection of
      Michigan Cancer Foundation-7 (MCF-7) human breast cancer cells and MUC1 biomarker
      by using an aptamer-based sandwich assay. A biocompatible nanocomposite
      consisting of multiwall carbon nanotubes (MWCNT) and poly(glutamic acid) is
      placed on a glassy carbon electrode (GCE). The sandwich assay relies on the use
      of a mucin 1 (MUC1)-binding aptamer that is first immobilized on the surface of
      modified GCE. Another aptamer (labeled with silver nanoparticles) is applied for
      secondary recognition of MCF-7 cells in order to increase selectivity and produce
      an amplified signal. Differential pulse anodic stripping voltammetry was used to
      follow the electrochemical signal of the AgNPs. Under the optimal condition, the
      sensor responds to MCF-7 cells in the concentration range from 1.0 * 102 to 1.0 *
      107 cells.mL-1 with a detection limit of 25 cells. We also demonstrate that the
      MUC1 tumor marker can be detected by the present biosensor. The assay is highly
      selective and sensitive, acceptably stable and reproducible. This warrants the
      applicability of the method to early diagnosis of breast cancer. Graphical
      abstract Schematic of the fabrication of an aptamer-based sandwich biosensor for
      Michigan Cancer Foundation-7 cells (MCF-7). A MWCNT-poly(glutamic acid)
      nanocomposite was used as a biocompatible matrix for MUC1-aptamer immobilization.
      Stripping voltammetry analysis of AgNPs was performed using aptamer conjugated
      AgNPs as signalling probe.

PMID- 30094652
TI  - On the Usage of Brain Atlases in Neuroimaging Research.
AB  - Brain atlases play a key role in modern neuroimaging analysis of brain structure
      and function. We review available atlas databases for humans and animals and
      illustrate common state-of-the-art workflows in neuroimaging research based on
      image registration. Advances in noninvasive imaging methods, 3D ex vivo
      microscopy, and image processing are summarized which will eventually close the
      current resolution gap between brain atlases based on conventional 2D histology
      and those based on 3D in vivo imaging.

PMID- 30094654
TI  - A mathematical model of CO2, O2 and N2 exchange during venovenous extracorporeal
      membrane oxygenation.
AB  - BACKGROUND: Venovenous extracorporeal membrane oxygenation (vv-ECMO) is an
      effective treatment for severe respiratory failure. The interaction between the
      cardiorespiratory system and the oxygenator can be explored with mathematical
      models. Understanding the physiology will help the clinician optimise therapy. As
      others have examined O2 exchange, the main focus of this study was on CO2
      exchange. METHODS: A model of the cardiorespiratory system during vv-ECMO was
      developed, incorporating O2, CO2 and N2 exchange in both the lung and the
      oxygenator. We modelled lungs with shunt fractions varying from 0 to 1, covering
      the plausible range from normal lung to severe acute respiratory distress
      syndrome. The effects on PaCO2 of varying the input parameters for the
      cardiorespiratory system and for the oxygenator were examined. RESULTS: PaCO2
      increased as the shunt fraction in the lung and metabolic CO2 production rose.
      Changes in haemoglobin and FIO2 had minimal effect on PaCO2. The effect of
      cardiac output on PaCO2 was variable, depending on the shunt fraction in the
      lung. PaCO2 decreased as extracorporeal circuit blood flow was increased, but the
      changes were relatively small in the range used clinically for vv-ECMO of > 2
      l/min. PaCO2 decreased as gas flow to the oxygenator rose and increased with
      recirculation. The oxygen fraction of gas flow to the oxygenator had minimal
      effect on PaCO2. CONCLUSIONS: This mathematical model of gas exchange during vv
      ECMO found that the main determinants of PaCO2 during vv-ECMO were pulmonary
      shunt fraction, metabolic CO2 production, gas flow to the oxygenator and
      extracorporeal circuit recirculation.

PMID- 30094657
TI  - Applying Social Cognitive Theory to Explore Relational Aggression across Early
      Adolescence: A Within- and Between-Person Analysis.
AB  - In the past two decades, there has been a significant amount of research on
      children's relational aggression, which has been found to be associated with
      psychosocial problems. Longitudinal studies have examined changes in relational
      aggression during early adolescence in relation to individual characteristics;
      however, most studies compare individual differences between people with regard
      to rates of relational aggression. A shortcoming to the current literature is the
      lack of studies that use a multilevel approach to examine individual differences
      (between-person) as well as the extent to which individuals deviate from their
      own typical levels (within-person) over time. In this study, within- and between
      person psychological and peer-related predictors of rates of relational
      aggression over time were examined. Participants included 1,655 students in 5th
      8th grade (mean age: 13.01) from four public middle schools in the Midwest, which
      consisted 828 females and 827 males. In terms of race and ethnicity, 819 (49.5%)
      were African Americans, followed by 571 (34.5%) Whites, and 265 (16%) Others.
      Longitudinal data were collected over four waves across two years of middle
      school. The findings indicated that contrary to the hypothesis that relational
      aggression would increase over time, there was no significant growth across time.
      Age, gender, and race were not associated with relational aggression over time;
      however, consistent with the Social Cognitive Theory, changes in within-person
      impulsivity, anger, and peer delinquency were all positively related to increases
      in relational aggression. At the between-person level of analysis, depressive
      symptoms and peer delinquency were related to relational aggression. Findings
      suggest that school-based programs that address anger management, impulsivity,
      empathy, and victimization could help prevent relational aggression.

PMID- 30094658
TI  - Self-Esteem and National Identification in Times of Islamophobia: A Study Among
      Islamic School Children in The Netherlands.
AB  - Despite strong debates about the role of Islamic education in Western societies,
      very little is known about the ways these schools can affect how Muslim children
      feel about these societies and themselves. This research examined how the self
      esteem and national identification of Islamic schools students in a non-Muslim
      country (N = 707; Mage = 10.02; SD = 1.25; 56.9% girls) depend on their
      perceptions of religious discrimination and the student-teacher relationship, as
      well as their teachers' religious background and implicit religious attitude.
      Children reported substantially more religious discrimination against their group
      than against themselves. Religious discrimination was associated with lower self
      esteem and weaker national identification, whereas a close bond with the teacher
      was associated with higher self-esteem and stronger national identification.
      Children with a non-Muslim teacher reported more national identification than
      students with a Muslim teacher, but less so if this teacher had a comparatively
      positive attitude toward Muslims. Results provide insights on how self-esteem and
      national identification can be encouraged within the context of Islamic
      education.

PMID- 30094659
TI  - [Coronary sinus mapping of the optimal LV electrode position].
AB  - Cardiac resynchronization therapy (CRT) is an established pillar of treatment for
      patients with chronic heart failure. However, 30% of patients do not respond
      adequately to this type of therapy. One possible reason for this is a nonoptimal
      left ventricular stimulation site. This review focuses on possibilities of
      visualization of the coronary vein anatomy and its role in the determination of
      the electrical and mechanical dyssynchrony to optimize the therapeutic success of
      the resynchronization therapy. In addition, the clinical implication and the
      perspectives of a dedicated mapping of the coronary vein are discussed. Finally,
      a brief outlook on current and future technologies for improving this form of
      therapy is given.

PMID- 30094661
TI  - ?

PMID- 30094660
TI  - Co-Delivery of Ciprofloxacin and Colistin in Liposomal Formulations with Enhanced
      In Vitro Antimicrobial Activities against Multidrug Resistant Pseudomonas
      aeruginosa.
AB  - PURPOSE: This study aims to develop liposomal formulations containing synergistic
      antibiotics of colistin and ciprofloxacin for the treatment of infections caused
      by multidrug-resistant Pseudomonas aeruginosa. METHODS: Colistin (Col) and
      ciprofloxacin (Cip) were co-encapsulated in anionic liposomes by ammonium sulfate
      gradient. Particle size, encapsulation efficiency, in vitro drug release and in
      vitro antibiotic activities were evaluated. RESULTS: The optimized liposomal
      formulation has uniform sizes of approximately 100 nm, with encapsulation
      efficiency of 67.0% (for colistin) and 85.2% (for ciprofloxacin). Incorporation
      of anionic lipid (DMPG) markedly increased encapsulation efficiency of colistin
      (from 5.4 to 67.0%); however, the encapsulation efficiency of ciprofloxacin was
      independent of DMPG ratio. Incorporation of colistin significantly accelerated
      the release of ciprofloxacin from the DMPG anionic liposomes. In vitro release of
      ciprofloxacin and colistin in the bovine serum for 2 h were above 70 and 50%. The
      cytotoxicity study using A549 cells showed the liposomal formulation is as non
      toxic as the drug solutions. Liposomal formulations of combinations had enhanced
      in vitro antimicrobial activities against multidrug resistant P. aeruginosa than
      the monotherapies. CONCLUSIONS: Liposomal formulations of two synergistic
      antibiotics was promising against multidrug resistant P. aeruginosa infections.

PMID- 30094662
TI  - Extravascular lung water index and Halperin score to predict outcome in
      critically ill patients.
AB  - OBJECTIVE: The aim of this study was to describe real world extravascular lung
      water index (EVLWI) measurements obtained by pulse index continuous cardiac
      output (PiCCO) on the day of admission. These were then related to a radiologic
      score for lung edema, Halperin score and both the Halperin score and EVLWI were
      assessed for prediction of in-hospital mortality in critically ill patients.
      METHODS AND RESULTS: A total of 311 patients admitted to a tertiary medical
      university hospital between February 2004 and December 2010 were included in this
      retrospective analysis and of these 177 patients were intubated. In-hospital
      mortality was assessed by logistic regression. In the overall cohort, EVLWI and
      the Halperin score correlated poorly (r = 0.17; p = 0.02). In intubated patients,
      EVLWI and Halperin score did not correlate (r = 0.09; p = 0.39), whereas in
      patients who were not intubated there was a moderate association (r = 0.30; p =
      0.007). In the overall cohort, (a) EVLWI (hazard ratio [HR] 1.10, 95% confidence
      interval [CI] 1.02-1.19; p = 0.01; area under the curve [AUC] 0.63, 95% CI 0.54
      0.71) but not (b) Halperin score (HR 1.00, 95% CI 0.996-1.004; p = 0.94; AUC
      0.52, 95% CI 0.45-0.58) was associated with in-hospital mortality There was a
      robust association of EVLWI (HR 1.12, 95% CI 1.01-1.25; p = 0.03) but not
      Halperin score (HR 1.003, 95% CI 0.997-1.009; p = 0.30) with mortality in non
      intubated patients. In intubated patients, neither EVLWI (HR 0.997 95% CI 0.990
      1.003; p = 0.33) nor Halperin score (HR 1.08; 95% CI 0.88-1.32; p = 0.47) was
      associated with mortality. CONCLUSION: The EVLWI correlated moderately with a
      radiologic score for lung edema, the Halperin score, in non-intubated but not in
      intubated patients. The EVLWI at admission was associated with in-hospital
      mortality in our patient collective of critically ill patients and might
      constitute not only a tool for risk stratification but most importantly a
      valuable treatment goal.

PMID- 30094663
TI  - Changes in health parameters in older lay volunteers who delivered a lifestyle
      based program to frail older people at home.
AB  - OBJECTIVE: To measure health effects in lay volunteers who made home visits
      consisting of social interaction, nutritional and physical exercise interventions
      to pre-frail and frail older people (trial registration ClinicalTrials.gov,
      NCT01991639). METHODS: After baseline, participants were followed-up at 12 (V1)
      and 24 (V2) weeks. A one-repetition maximum (1-RPM) and handgrip were measured
      with the Concept2(r)DYNO and a dynamometer. The Physical Activity Scale for the
      Elderly was used to assess physical activity, and Food Frequency Questionnaire
      and the Mediterranean Diet Adherence Screener for nutrition. Additionally,
      quality of life (QoL) was measured with the World Health Organization (WHO)
      quality of life brief questionnaire and anthropometric measurements were
      performed using bioelectrical impedance analysis. RESULTS: Handgrip values
      significantly increased from 32.14 +/- 7.94 kg to 33.69 +/- 6.72 kg at V1 and
      34.36 +/- 6.96 kg at V2. The 1-RPM on the leg press showed a significant increase
      from 72.47 +/- 25.37 kg to 78.12 +/- 23.77 kg and 80.85 +/- 27.99 kg,
      respectively. We observed a significant decrease of protein intake from 0.38 +/-
      0.26 g/kgBW/day to 0.32 +/- 0.19 g/kgBW/day and 0.26 +/- 0.16 g/kgBW/day,
      respectively. There were no changes in physical activity, QoL and anthropometric
      measurements. CONCLUSION: The findings indicate that projects involving aging
      healthy volunteers may have additional limited health benefits.

PMID- 30094664
TI  - Prioritizing information topics for relatives of critically ill patients : Cross
      sectional survey among intensive care unit relatives and professionals.
AB  - A patient's admission to an intensive care unit (ICU) has a significant impact on
      family members and other relatives. In order for them to be able to cope with
      such a stressful situation, the availability of appropriate understandable and
      accessible information is crucial. The information asymmetry between relatives
      and medical professionals may adversely affect satisfaction of relatives and
      their risk of subsequent anxiety, depression and stress symptoms. The aim of this
      study was therefore to understand which topics are most important to the
      relatives of ICU patients and to quantify the perceptions of medical
      professionals regarding the information needs of relatives. A cross-sectional
      survey was conducted in 2015. The survey had 42 questions, such as 'diagnosis',
      'treatment', 'comfort', 'family' and 'end of life'. In total, the survey was
      handed out to four different groups. A total of 336 persons answered the survey
      (26 relatives, 28 ICU physicians, 202 ICU nurses and 80 ICU medical professionals
      in a closed Facebook(c) group [Facebook, Menlo Park, California, USA]). Relatives
      ranked the five most important topics as follows: 'recent events (crisis)', 'my
      participation', 'contamination in hospital', 'physical pain', and 'probability'.
      Several significant differences (p<0.001) were detected, for example for the
      topics fever, medication, recent events (crisis), appointments, relapse, and
      investigations. Even the topic with the lowest ranking (religion) had a score of
      3.15 (min. 1.00, max. 5.00) among relatives. The ICU professionals appear to have
      divergent opinions regarding the most important topics for ICU relatives as
      compared to relatives themselves.

PMID- 30094665
TI  - Behavioral Genetics and Attributions of Moral Responsibility.
AB  - While considerable research has examined how genetic explanations for behavior
      impact assessments of moral responsibility, results across studies have been
      inconsistent. Some studies suggest that genetic accounts diminish ascriptions of
      responsibility, but others show no effect. Nonetheless, conclusions from behavior
      genetics are increasingly mobilized on behalf of defendants in court, suggesting
      a widespread intuition that this sort of information is relevant to assessments
      of blameworthiness. In this paper, we consider two sorts of reasons why this kind
      of intuition, if it exists, is not consistently revealed in empirical studies. On
      the one hand, people may have complex and internally conflicting intuitions about
      the relationship between behavior genetics and moral responsibility. On the other
      hand, it may be that people are motivated to think about the role of genetics in
      behavior differently depending on the moral valence of the actions in question.

PMID- 30094666
TI  - Nematicidal potential of Taraxacum officinale.
AB  - This study was aimed to investigate the activity of the Asteraceae species
      Taraxacum officinale against the root-knot nematode Meloidogyne incognita. Leaf
      and root extracts of T. officinale were tested in vitro at a range of 62.5-1000
      and 250-1000 MUg mL-1 concentrations on nematode juveniles and eggs,
      respectively, whereas treatments with 10-40 g kg-1 soil rates of dry leaf and
      root T. officinale biomass were applied to soil infested by M. incognita in
      greenhouse experiments on potted tomato. Peak 36 and 50% juvenile mortality and
      14.8 and 23.8% egg hatchability reduction were recorded at the maximum
      concentration of leaf and root extracts, respectively. Soil treatments with T.
      officinale leaf and root material strongly suppressed nematode multiplication and
      gall formation on tomato roots and significantly increased plant growth. Chicoric
      acid and 3-O- and 3,5-di-O-caffeoylquinic acid were found to be the main
      components of leaf and root extract, respectively, and proved, as the total
      hydroalcoholic extracts from T. officinale leaf and root material, for an
      antioxidant activity. Data from this study indicate the suitability of plant
      materials from T. officinale for a potential formulation of nematicidal products
      to include in sustainable nematode management strategies.

PMID- 30094668
TI  - Behavior and histopathology as biomarkers for evaluation of the effects of
      paracetamol and propranolol in the neotropical fish species Phalloceros harpagos.
AB  - Pharmaceutical drugs in the aquatic environment can induce adverse effects on
      nontarget organisms. This study aimed to assess the short-term effects of
      sublethal concentrations of both paracetamol and propranolol on the fish
      Phalloceros harpagos, specifically light/dark preference, swimming patterns, skin
      pigmentation, histopathology, and liver glycogen levels. Fish were acutely
      exposed to sublethal concentrations of both paracetamol (0.008, 0.08, 0.8, 8, 80
      mg L-1) and propranolol (0.0001, 0.001, 0.01, 0.1, 1 mg L-1) under controlled
      conditions. For scototaxis, a significant preference for the dark compartment was
      observed for the group exposed to the highest concentration of paracetamol (80 mg
      L-1). Propranolol exposure significantly altered the swimming pattern, especially
      in fish exposed to the 0.001 mg L-1 concentration. Pigmentation was reduced in
      propranolol-exposed fish (0.1, 1 mg L-1). The lowest concentration of propranolol
      (0.0001 mg L-1) induced a decrease of histochemical reaction for hepatic
      glycogen. These data demonstrate that pharmaceuticals can induce sublethal
      effects in nontarget organisms, even at low concentrations, compromising specific
      functions of the individual with ecological relevance, such as energy balance and
      behavior.

PMID- 30094667
TI  - Answers to the comments on "Air pollution, biological marker and lung function in
      children".

PMID- 30094669
TI  - Selenium and drinking water quality indicators in Mongolia.
AB  - Mongolia is characterized by restricted sources of drinking water and intensive
      water pollution due to high rates of urbanization, mining industry development,
      enormous amount of livestock, and ever-growing attempts in domestic production of
      cereals and vegetables. Among others, Se is the least studied element in
      Mongolian water resources. Based on fluorimetric method of analysis, the first
      results on Se levels in drinking water of five aimags, Ulaanbaatar, and Erdenet
      were obtained. Uneven distribution of Se in Mongolia was manifested, the highest
      Se concentrations being typical for the southern resources (up to 18,600 MUg/L)
      and the lowest, for the Northern ones (up to 0.022 MUg/L). ICP-MS data of Al, As,
      B, Ca, Cd, Co, Cr, Cu, Fe, Hg, I, K, Li, Mg, Mn, Na, Ni, P, Pb, Si, Sn, Sr, V,
      and Zn contents indicate poly-microelementosis existence in the South of Mongolia
      (Dorno-Gobi aimag) where ground water is characterized by elevated levels of As
      and extremely high levels of Se, Li, Na, F, Cl, B, and nitrates ions, exceeding
      maximum permissible levels by 1.86; 4.3; 3.1; 3.1; 2.7; 3.4; and 1.8 times
      respectively. Toxic concentrations of Se in groundwater of Dorno-Gobi aimag
      contradict with the published low human serum Se and low content of the element
      in horseflesh that suggests the possible effect of the above pollutants on Se
      bioavailability. Revealed phenomenon and mosaic distribution of heavy metals in
      areas with high and low Se content in water resources indicate the need of direct
      search for Se and other pollutant transfer in food chain in various ecological
      loading conditions, creation of a map of Se distribution in water resources of
      other Mongolian regions, and large-scale evaluation of the human poly-elemental
      status.

PMID- 30094670
TI  - Effects of biological clogging on 1,1,1-TCA and its intermediates distribution
      and fate in heterogeneous saturated bio-augmented permeable reactive barriers.
AB  - Biological clogging in porous media was an important concern in the design of bio
      augmented permeable reactive barriers (Bio-PRBs) that were used to remediate
      groundwater with dense non-aqueous phase liquids (DNAPLs). Here, we used
      laboratory sandbox experiments to develop and calibrate reactive transport models
      (C1 and C2) simulating 1,1,1-trichloroethane (1,1,1-TCA) change in heterogeneous
      saturated porous media. The routine (1,1,1-TCA chain kinetic reactions) and
      subroutine (the relationship between hydraulic conductivity (K) and time (t))
      were included in the model computer code. The simulation results suggested that
      the model C1 had the applicability for simulating contaminant transport and fate
      in bio-augmented flow field. By using the model C1 which was suitable for
      constant K condition, the performance of different types of Bio-PRBs was
      evaluated, and the regularity of contaminants chain kinetic reactions in
      different heterogeneous saturated porous media was obtained. The results
      demonstrated that Bio-PRBs in immobilized microorganism (IM) protocol were more
      superior to Bio-PRBs in free microorganism (FM) protocol. In addition, by using
      the model C2 (updated model C1) which was suitable for decreasing K condition,
      the different and optimized regularity of contaminants transport and
      transformation was obtained. The results showed that microbial growth which
      further decreased K was beneficial to preventing the transport of contaminants
      and accelerating the transformation of contaminants. However, the negative
      effects of biological clogging on hydraulic conductivity and relative hydraulic
      conductivity ratio in FM Bio-PRBs were significantly stronger than that in IM Bio
      PRBs. Deploying IM Bio-PRBs for groundwater remediation would be much more
      efficient and meet the design criteria. The research work had guiding
      significance to engineering and provided consultation for designing and
      optimizing Bio-PRBs system. To make the design and optimization of Bio-PRBs
      system convenient, it was very essential to choose the suitable mathematical
      model (C1 or C2).

PMID- 30094671
TI  - Response of soil phosphatase activities to contamination with two types of tar
      oil.
AB  - Tar oil is a complex mixture of hydrocarbon compounds obtained from high
      temperature distillation of coal tar. It has been used for over 100 years from
      now to protect wood and has been applied to wood products, primary utility poles,
      and railroad ties by pressure methods. Composition of the tar oil depends on the
      source and typically consists of 85% polycyclic aromatic hydrocarbons (PAHs), 10%
      phenolic compounds, and 5% heterocyclic compounds. In this research, we performed
      the laboratory experiment to compare two types of tar oil: C and GX-Plus, and
      their effects on P-cycling enzymes (phosphatases) in sandy loam and loamy sand.
      Tar oil was applied to soil samples at the following doses: 2, 10, and 50 g kg-1.
      Soil without tar oil was used as a control sample. The experiment showed that the
      contamination of soil with tar oil affects the enzyme activities measured and
      with this most probably the P-cycle in soil. Phosphomonoesterases were the most
      sensitive to the contamination of soil with both type of tar oil: typeC and type
      GX-Plus. Greater changes in the enzymatic activity were observed in the loamy
      sand. Moreover, the type C tar oil demonstrated higher toxicity for phosphatases
      than type GX-Plus.

PMID- 30094672
TI  - Air pollution, biological marker and lung function in children.

PMID- 30094673
TI  - Kinetics, isotherm, and optimization of the hexavalent chromium removal from
      aqueous solution by a magnetic nanobiosorbent.
AB  - Sorption is the most effective approach to the treatment of acid mine drainage
      (AMD) and wastewaters, but the removal of the adsorbents from water has always
      been a challenging problem which may be resolved by using magnetic separation. In
      this work, a magnetic bioadsorbent was prepared using low cost and high
      performance sources and applied in Cr(VI) removal from a synthetic solution.
      Initially, magnetite nanoparticles were synthesized from iron boring scraps by
      chemical co-precipitation method. Results of dynamic light scattering (DLS) and
      vibrating sample magnetometry (VSM) analyses showed that the synthesized
      nanoparticles were around 40 nm in size and had a significant magnetization.
      Then, the magnetite nanoparticles were attached to the dead and alkaline
      activated biomass of Aspergillus niger. Central composite design (CCD) was
      applied to determine the optimal condition of Cr(VI) adsorption on the produced
      magnetic nanobiocomposite. The maximum chromium removal (~ 92%) was achieved at
      pH 5.8, Cr concentration 23.4 mg/l, adsorbent dose 3.72 g/l, agitation rate 300
      rpm, and duration 11 min. Kinetic studies showed that regardless of temperature,
      the process was controlled by mass transfer and intraparticle diffusion with an
      equilibrium constant of 0.74 mg/g min1/2 at 40  degrees C. Also, the adsorption
      isotherms followed the Temkin model, which indicated the physical adsorption of
      Cr(VI) on the produced sorbent. Therefore, the magnetic nanobiocomposite has a
      perfect ability to be used as the chromium adsorbent and can be collected by a
      low external magnetic field. Graphical abstract Synthesis of the magnetic
      nanobiosorbent and its application in the removal of Cr(VI) from wastewaters.

PMID- 30094674
TI  - Tracing the sources of suspended sediment and particle-bound trace metal elements
      in an urban catchment coupling elemental and isotopic geochemistry, and fallout
      radionuclides.
AB  - The excessive supply of contaminants from urban areas to rivers during the last
      centuries has led to deleterious impacts on aquatic ecosystems. The sources, the
      behavior, and the dynamics of these contaminants must be better understood in
      order to reduce this excessive anthropogenic pollution. Accordingly, the current
      research investigated the particle-bound trace element (TE) contamination of the
      900-km2 Orge River (Seine basin, France) and the potential sources of these
      particles (agricultural or forest soils, channel banks, road deposited
      sediments), through the analysis of multiple fallout radionuclides, elemental
      geochemistry, and lead isotopic composition on suspended particulate matter (SPM)
      collected during a hydrological year at four stations following an increasing
      urbanization gradient (300 to 5000 inhab.km-2). Fallout radionuclide measurements
      showed an increasing contribution of recently eroded particles from urban areas
      to the SPM in downstream direction. However, this contribution varied depending
      on hydrological conditions. A greater contribution of particles originating from
      urban areas was observed during low stage periods. On the contrary, the
      contribution of agricultural soils and channel banks that are less enriched in
      contaminants and fallout radionuclides was higher during seasonal floods, which
      explained the dilution of radionuclide contents in sediment transiting the river
      during those events. Trace element contamination of SPM in Cu, Zn, Pb, and Sb
      increased from moderate to significant levels with urban pressure in downstream
      direction (with corresponding enrichment factors raising from 2 to 6). In
      addition, Pb isotopic ratios indicated that the main source of Pb corresponded to
      the "urban" signature found in road deposited sediments. The low variations in
      lead isotope ratios found in the SPM for contrasting hydrological conditions
      demonstrated the occurrence of a single source of Pb contamination. These results
      demonstrate the need to better manage urban runoff during both flood and low
      precipitation events to prevent the supply of diffuse particle-bound
      contamination to rivers draining urban areas.

PMID- 30094675
TI  - Development of hybrid processes for the removal of volatile organic compounds,
      plasticizer, and pharmaceutically active compound using sewage sludge, waste
      scrap tires, and wood chips as sorbents and microbial immobilization matrices.
AB  - This study evaluated the reutilization of waste materials (scrap tires, sewage
      sludge, and wood chips) to remove volatile organic compounds (VOCs)
      benzene/toluene/ethylbenzene/xylenes/trichloroethylene/cis-1,2-dichloroethylene
      (BTEX/TCE/cis-DCE), plasticizer di(2-ethylhexyl) phthalate (DEHP), and
      pharmaceutically active compound carbamazepine from artificially contaminated
      water. Different hybrid removal processes were developed: (1) 300 mg/L BTEX + 20
      mg/L TCE + 10 mg/L cis-DCE + tires + Pseudomonas sp.; (2) 250 mg/L toluene +
      sewage sludge biochar + Pseudomonas sp.; (3) 100 mg/L DEHP + tires +
      Acinetobacter sp.; and (4) 20 mg/L carbamazepine + wood chips + Phanerochaete
      chrysosporium. For the hybrid process (1), the removal of xylenes, TCE, and cis
      DCE was enhanced, resulted from the contribution of both physical adsorption and
      biological immobilization removal. The hybrid process (2) was also superior for
      the removal of DEHP and required a shorter time (2 days) for the bioremoval. For
      the process (3), the biochar promoted the microbial immobilization on its surface
      and substantially enhanced/speed up the bioremoval of toluene. The fungal
      immobilization on wood chips in the hybrid process (4) also improved the
      carbamazepine removal considerably (removal efficiencies of 61.3 +/- 0.6%)
      compared to the suspended system without wood chips (removal efficiencies of 34.4
      +/- 1.8%). These hybrid processes would not only be promising for the
      bioremediation of environmentally concerned contaminants but also reutilize waste
      materials as sorbents without any further treatment.

PMID- 30094677
TI  - Perceived Discrimination and Major Depression and Generalized Anxiety Symptoms:
      In Muslim American College Students.
AB  - Prior research has found that Muslim Americans' discrimination experiences are
      associated with increased risk of mental health problems. However, few studies
      have included Muslim American college students or identified moderators of this
      relationship. Among a sample of Muslim American college students (N = 141), the
      current study found that perceived discrimination was positively associated with
      MD and GAD symptom severity. Having a strong Muslim American identity exacerbated
      the relationship between perceived discrimination and GAD symptoms. The findings
      support practices to reduce discrimination toward Muslim American college
      students and the need for outreach to students with a strong Muslim American
      identity.

PMID- 30094676
TI  - The relationship between diabetes, prostate-specific antigen screening tests, and
      prostate cancer.
AB  - PURPOSE: Men with diabetes have been found to have a reduced risk of prostate
      cancer (PCa), potentially due to detection bias from lower prostate-specific
      antigen (PSA) levels or inhibition of tumor growth. Understanding if lower PCa
      rates are due to a lower risk of the disease or a detection bias from PSA testing
      can help inform the benefits and harms from prostate cancer screening. METHODS:
      We used data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Screening
      Trial to assess the impact of PSA screening on PCa in men with diabetes and the
      potential role of detection bias and/or slower tumor growth. Comparing men by
      diabetes status, we calculated age-adjusted incidence rates by tumor grade and
      compared screening results, PSA levels, and tumor characteristics. RESULTS: Men
      with diabetes had lower rates of PCa but was limited to low- and intermediate
      grade tumors. Men with diabetes were less likely to be biopsied after their first
      positive screening test and men diagnosed with low/intermediate-grade tumors had
      significantly more advanced tumors with higher PSA levels. CONCLUSIONS: Our
      findings provide additional evidence that detection bias is likely contributing
      to the lower rates of low- and intermediate-grade prostate cancers.

PMID- 30094678
TI  - A Qualitative Examination of VA Chaplains' Understandings and Interventions
      Related to Moral Injury in Military Veterans.
AB  - This study examines VA chaplains' understandings of moral injury (MI) and
      preferred intervention strategies. Drawing qualitative responses with a
      nationally-representative sample, content analyses indicated that chaplains'
      definitions of MI comprised three higher order clusters: (1) MI events, (2)
      mechanisms in development of MI, and (3) warning signs of MI. Similarly,
      chaplains' intervention foci could be grouped into three categories: (1)
      pastoral/therapeutic presence, (2) implementing specific interventions, and (3)
      therapeutic processes to promote moral repair. Findings are discussed related to
      emerging conceptualizations of MI, efforts to adapt existing evidence-based
      interventions to better address MI, and the potential benefits of better
      integrating chaplains into VA mental health service delivery.

PMID- 30094680
TI  - Interactive effects of temperature and salinity on the survival, oxidative
      stress, and Na+/K+-ATPase activity of newly hatched obscure puffer (Takifugu
      obscurus) larvae.
AB  - Obscure puffer (Takifugu obscurus) is an anadromous fish widely distributed
      around the coastal and inland rivers in East Asia. T. obscurus often encounters
      fluctuations in temperature and salinity. This study aimed to investigate the
      effect of the interactions of temperature and salinity on survival and oxidative
      stress response of newly hatched T. obscurus larvae. A combination of three
      temperatures (19, 25, and 31  degrees C) and three salinities (0, 10, and 20 ppt)
      was applied for 96 h under laboratory conditions. The newly hatched larvae could
      not tolerate 31  degrees C for 96 h. No death was recorded at other temperatures
      during this experiment. Malondialdehyde concentrations increased significantly
      after 6 h of exposure to high salinity (10 and 20 ppt) and then decreased until
      the end of the experiment at each temperature. The highest superoxide dismutase
      activity was observed under the exposure to 20 ppt for 24 h at 31  degrees C.
      Na+/K+-ATPase activity significantly increased as salinity increased, especially
      at low temperatures. With the prolong of exposure time, the integrated biomarker
      response (IBR) values showed an increase until 48 h and then declined at 96 h in
      most treatments. The largest IBR value appeared when larvae were exposed to the
      highest temperature and salinity for 24 h. Our study indicated that high
      temperature with high salinity may negatively affect the early development of T.
      obscurus and their combined effects should be considered in the larvae culture.

PMID- 30094681
TI  - The sbGnRH-GTH system in the female short mackerel, Rastrelliger brachysoma
      (Bleeker, 1851), during breeding season: implications for low gamete production
      in captive broodstock.
AB  - The short mackerel (Rastrelliger brachysoma) is one of the most economically
      important fish in Thailand; it is also a prime candidate for mariculture but
      unfortunately is plagued by reproductive problems that cause low production of
      gametes in captivity. An understanding of how the brain, pituitary, and gonad
      axis (BPG) from the neuroendocrine system are involved in the reproductive
      activity of wild and captive R. brachysoma should help clarify the situation. In
      this study, we investigated changes in the sea bream gonadotropin-releasing
      hormone (sbGnRH)-gonadotropin (GTH) system in the female short mackerel,
      Rastrelliger brachysoma (Bleeker, 1851), during breeding season. sbGnRH
      immunoreactive (ir) cell bodies were detected in the nucleus preopticus
      periventricularis including nucleus periventricularis (NPT), nucleus preopticus
      (Np), and nucleus lateralis tuberis (NLT). Additionally, the sbGnRH-ir fibers
      protruded into the proximal par distalis (PPD) where GTH (FSH and LH) cells were
      detected. The number of sbGnRH-ir cell bodies and GTH cells and level of LH mRNA
      were significantly higher in the breeding season than those in the non-breeding
      season. Moreover, the number of sbGnRH-ir cell bodies and GTH cells and levels of
      sbGnRH and GTH (FSH and LH) mRNA were significantly higher in the wild fish than
      those in the cultured broodstock. It is suggested that the wild fish tended to
      have better reproductive system than hatchery fishes. This could be related to
      the endocrinological dysfunction and the reproductive failure in the hatchery
      condition. Moreover, the changes of all of the hormonal level could potentially
      be applied to R. brachysoma aquaculture.

PMID- 30094679
TI  - Sex Differences in Insomnia: from Epidemiology and Etiology to Intervention.
AB  - PURPOSE OF REVIEW: Insomnia is approximately 1.5 times more common in women than
      in men. To date, research has advanced our knowledge about why women report
      significantly more sleep problems than men despite not being reflected in
      objective sleep measures. Precisely understanding the symptomatology and
      pathological mechanisms underlying sex differences is important for prevention
      and providing appropriate interventions. RECENT FINDINGS: Sex differences found
      in insomnia goes beyond simple explanations and have been proven to be a
      complicated interplay of biological, psychological, and social factors that play
      different roles throughout the life span. This paper will review sex differences
      in insomnia based on risk factors, mechanisms, and consequences, as well as
      treatment response. In addition, we will also discuss treatment recommendations
      when working with female populations at different stages in the life span that
      may be more vulnerable to insomnia. Future studies utilizing prospective,
      longitudinal designs are needed to understand the interactions of various factors
      that can explain existing sex differences in insomnia.

PMID- 30094682
TI  - Myocardial bridging, a trigger for Takotsubo syndrome.

PMID- 30094684
TI  - M2 macrophages and their role in rheumatic diseases.
AB  - As a component of the innate immune system, macrophages play a crucial role in
      host defense against a variety of microbes. Conventionally, macrophages have been
      classified as M1 and M2 depending on their phenotype and role in immune
      regulation. M1 macrophages are generally pro-inflammatory, while M2 (also known
      as alternatively activated macrophages) are anti-inflammatory. M1 macrophages
      release pro-inflammatory cytokines, reactive nitrogen, and oxygen intermediates,
      and kill pathogens, whereas their M2 counterparts participate in the resolution
      of inflammation, remodeling of tissue, angiogenesis, and tissue repair.
      Macrophages are also crucial in the pathogenesis of immune-inflammatory
      disorders, such as, arthritis. In this review, we discuss the markers of human M2
      macrophages, the role played by them in inflammation or progression of rheumatic
      diseases, their potential to act as biomarkers, and, finally, therapeutic
      strategies aiming at altering/enhancing the macrophage phenotype.

PMID- 30094683
TI  - SPICES: a particle-based molecular structure line notation and support library
      for mesoscopic simulation.
AB  - Simplified Particle Input ConnEction Specification (SPICES) is a particle-based
      molecular structure representation derived from straightforward simplifications
      of the atom-based SMILES line notation. It aims at supporting tedious and error
      prone molecular structure definitions for particle-based mesoscopic simulation
      techniques like Dissipative Particle Dynamics by allowing for an interplay of
      different molecular encoding levels that range from topological line notations
      and corresponding particle-graph visualizations to 3D structures with support of
      their spatial mapping into a simulation box. An open Java library for SPICES
      structure handling and mesoscopic simulation support in combination with an open
      Java Graphical User Interface viewer application for visual topological
      inspection of SPICES definitions are provided.

PMID- 30094686
TI  - The Risk of Takotsubo Cardiomyopathy in Acute Neurological Disease.
AB  - BACKGROUND: Case series have reported reversible left ventricular dysfunction,
      also known as stress cardiomyopathy or Takotsubo cardiomyopathy (TCM), in the
      setting of acute neurological diseases such as subarachnoid hemorrhage. The
      relative associations between various neurological diseases and Takotsubo remain
      incompletely understood. METHODS: We performed a cross-sectional study of all
      adults in the National Inpatient Sample, a nationally representative sample of US
      hospitalizations, from 2006 to 2014. Our exposures of interest were primary
      diagnoses of acute neurological disease, defined by ICD-9-CM diagnosis codes. Our
      outcome was a diagnosis of TCM. Binary logistic regression models were used to
      examine the associations between our pre-specified neurological diagnoses and TCM
      after adjustment for demographics. RESULTS: Among acute neurological diagnoses,
      the strongest associations were seen with subarachnoid hemorrhage (odds ratio
      [OR] 11.7; 95% confidence interval [CI] 10.2-13.4), status epilepticus (OR 4.9;
      95% CI 3.7-6.3), and seizures (OR 1.3; 95% CI 1.1-1.5). In a sensitivity analysis
      including secondary diagnoses of acute neurological diagnoses, associations were
      also seen with transient global amnesia (OR 2.3; 95% CI 1.5-3.6),
      meningoencephalitis (OR 2.1; 95% CI 1.7-2.5), migraine (OR 1.7; 95% CI 1.5-1.8),
      intracerebral hemorrhage (OR 1.3; 95% CI 1.1-1.5), and ischemic stroke (OR 1.2;
      95% CI 1.1-1.3). In addition, female sex was strongly associated with Takotsubo
      (OR 5.1; 95% CI 4.9-5.4). CONCLUSION: TCM appears to be associated with varying
      degrees with several acute neurological diseases besides subarachnoid hemorrhage.

PMID- 30094685
TI  - Ankylosing spondylitis causes high burden to patients and the healthcare system:
      results from a German claims database analysis.
AB  - To compare healthcare resource utilization and costs between ankylosing
      spondylitis (AS) patients and a matched sample from the general population
      without AS covered by the German Statutory Health Insurance (SHI) system, a non
      interventional retrospectively matched cohort analysis was conducted using
      anonymized SHI claims data. Data from January 1st, 2011 through December 31st,
      2014 were analyzed. Individuals with a coded diagnosis of AS during the
      enrollment period comprising the full year of 2013 were directly matched (1:5) to
      individuals without AS diagnosis in the whole study period by age, gender,
      hospitalizations, and comorbidities. All-cause healthcare resource utilization
      and direct costs were analyzed for the year 2013. Statistical tests were applied
      to compare the differences between the two sampled populations. In 2013, 10,208
      AS patients were identified and matched to a sample of 51,040 patients without AS
      from the general population. Healthcare resource utilization was significantly
      higher in all healthcare sectors (inpatient, outpatient, pharmaceuticals,
      remedies, devices and aids, and sick leave) in the AS cohort. Mean all-cause
      healthcare costs per patient were about ?2475 higher in the AS cohort compared to
      the general population. Most important cost drivers were hospitalizations and
      pharmaceuticals in terms of bDMARDs prescribed in 10% of the patients. Real-world
      data from this German claims database analysis showed that AS is associated with
      a substantial incremental economic burden to the healthcare system.

PMID- 30094688
TI  - Multi-Objective Cognitive Model: a Supervised Approach for Multi-subject fMRI
      Analysis.
AB  - In order to decode human brain, Multivariate Pattern (MVP) classification
      generates cognitive models by using functional Magnetic Resonance Imaging (fMRI)
      datasets. As a standard pipeline in the MVP analysis, brain patterns in multi
      subject fMRI dataset must be mapped to a shared space and then a classification
      model is generated by employing the mapped patterns. However, the MVP models may
      not provide stable performance on a new fMRI dataset because the standard
      pipeline uses disjoint steps for generating these models. Indeed, each step in
      the pipeline includes an objective function with independent optimization
      approach, where the best solution of each step may not be optimum for the next
      steps. For tackling the mentioned issue, this paper introduces Multi-Objective
      Cognitive Model (MOCM) that utilizes an integrated objective function for MVP
      analysis rather than just using those disjoint steps. For solving the integrated
      problem, we proposed a customized multi-objective optimization approach, where
      all possible solutions are firstly generated, and then our method ranks and
      selects the robust solutions as the final results. Empirical studies confirm that
      the proposed method can generate superior performance in comparison with other
      techniques.

PMID- 30094687
TI  - Use and Effectiveness of Antimicrobial Intravesical Treatment for Prophylaxis and
      Treatment of Recurrent Urinary Tract Infections (UTIs): a Systematic Review.
AB  - PURPOSE OF REVIEW: Intravesical antibiotics (IVA) has been used for prophylaxis
      and treatment of recurrent urinary tract infections (rUTIs). However, there is a
      lack of comprehensive evidence and consensus on its use. We conducted a
      systematic review to collect all available data about the effectiveness of IVA in
      prevention and treatment of rUTIs and to give an overview on the outcomes to
      date. METHODS: A systematic review was carried out for all English language
      articles from inception to August 2017, according to the Cochrane and PRISMA
      standards using MEDLINE, Scopus, Biomed Central, EMBASE, CINAHL, and Web of
      Science with references cross-checked and individual urology journals hand
      searched. RESULTS: After an initial identification of 658 studies, we screened 37
      abstracts and 18 full-text papers of which 11 were included in our final review.
      This included 285 patients with a mean age of 52 years and a female:male ratio of
      129:117. The IVA used was gentamicin, neomycin/polymyxin, neomycin or colistin
      and IVA was used for rUTIs as prophylaxis in 5 studies (n = 168) and treatment in
      6 studies (n = 117). Overall, a good reduction in symptomatic UTI was seen in
      78%, with a short-term success rate and discontinuation rates of 71% (120/168)
      and 8% (14/168) in the prophylaxis group and 88% (103/117) and 5% (6/117) in the
      treatment groups respectively. There was a change in the sensitivity of organisms
      in 30% (50/168) and 23% (27/117) in the treatment and prophylaxis groups
      respectively. Twenty patients discontinued their IVA instillations which were
      higher for the non-gentamicin group (11%) compared to the gentamicin group (5%).
      The side effects were minor and included allergy, suprapubic discomfort,
      autonomic dysreflexia, urinary tract infections and diarrhoea. Intravesical
      antimicrobial instillation seems to be a relatively safe and effective method for
      the prophylaxis and treatment of recurrent UTIs, especially in the short term. It
      gives clinicians an alternative treatment modality in high-risk patients
      predisposed to UTIs where all other forms of systemic treatments have failed.

PMID- 30094689
TI  - Successful recovery of sensation loss in upper brachial plexus injuries.
AB  - OBJECTIVE: Injuries of the upper trunk of the brachial plexus may trigger motor
      and sensory deficits. There exists a growing body of literature with respect to
      the reconstruction of motor deficits in upper trunk brachial plexus injuries by
      using nerve transfers; albeit to date, very few old reports have focused on the
      reconstruction of sensory loss resulting from upper trunk injuries. In this case
      series, we review six cases (five males and one female) with upper trunk brachial
      plexus injuries undergoing sensory nerve transfers. METHODS: Sensory
      reconstruction was carried out by using transfer of the ulnar to the median
      nerves, innervating adjacent aspects of the little and ring fingers (the fourth
      web space) and adjacent aspects of the thumb and the index finger (the first web
      space), respectively. RESULTS: The mean age of our six patients was 30.5 +/- 9
      years old (range 20-45). The mean time interval between the injury and subsequent
      surgery was 6.6 +/- 1.8 months (range 5-10). Five patients achieved S3 or S3+ in
      both the thumb and the index finger while the sixth one regained S2+ in the index
      finger while also achieving S3 in the thumb according to the Highet-Zachary
      system scoring scale. CONCLUSION: These results suggest that nerve transfers can
      achieve satisfactory outcomes in patients having sensory reconstruction after
      upper brachial plexus injuries, and thus, we lay emphasis on reviving the use of
      sensory nerve transfer techniques in such patients.

PMID- 30094690
TI  - Incidental finding of a mass fitting into a patent foramen ovale.

PMID- 30094691
TI  - Effects of elevated atmospheric CO2 and increased tidal flooding on leaf gas
      exchange parameters of two common mangrove species: Avicennia marina and
      Rhizophora stylosa.
AB  - In this study, we examined interactive effects of elevated atmospheric CO2,
      concentrations, and increased tidal flooding on two mangroves species, Avicennia
      marina and Rhizophora stylosa. Leaf gas-exchange parameters (photosynthesis,
      transpiration rates, water-use efficiency, stomatal conductance, and dark
      respiration rates) were measured monthly on more than 1000 two-year-old seedlings
      grown in greenhouses for 1 year. In addition, stomatal density and light curve
      responses were determined at the end of the experiment. Under elevated CO2
      concentrations (800 ppm), the net photosynthetic rates were enhanced by more than
      37% for A. marina and 45% for R. stylosa. This effect was more pronounced during
      the warm season, suggesting that an increase in global temperatures would further
      enhance the photosynthetic response of the considered species. Transpiration
      rates decreased by more than 15 and 8% for A. marina and R. stylosa,
      respectively. Consequently, water-use efficiency increased by 76% and 98% for A.
      marina and R. stylosa, respectively, for both species, which will improve drought
      resistance. These responses to elevated CO2 were minimized (by 5%) with longer
      flooding duration. Consequently, future increases of atmospheric CO2 may have a
      strong and positive effect on juveniles of A. marina and R. stylosa during the
      next century, which may not be suppressed by the augmentation of tidal flooding
      duration induced by sea-level rise. It is possible that this effect will enhance
      seedling dynamic by increasing photosynthesis, and therefore will facilitate
      their settlements in new area, extending the role of mangrove ecosystems in
      carbon sequestration and climate change mitigation.

PMID- 30094693
TI  - Results of weekday-on and weekend-off administration schedule of sunitinib
      therapy for advanced renal cell carcinoma.
AB  - BACKGROUND: Sunitinib is widely prescribed as first-line therapy for metastatic
      renal cell carcinoma. To reduce the ratio of severe adverse events and improve
      the relative dose intensity, we prospectively tried our own alternative
      medication schedule, which we called the "weekday-on and weekend-off regimen".
      Here we report the results of this regimen compared to the conventional
      medication schedule. METHODS: In total, 58 patients were enrolled in this study.
      Twenty patients were treated under the alternative schedule (group I: weekday-on
      and weekend-off regimen) and 38 patients were treated using the conventional
      schedule (group II: 4 weeks on and 2 weeks off regimen). The relative dose
      intensity (6W-RDI) and prognoses were compared between the two groups. RESULTS:
      Median 6W-RDI of all the patients was 75.0%. Group I patients demonstrated
      significantly higher 6W-RDI compared to group II (77.2 vs. 70.4%) (p = 0.019).
      Multivariate analysis showed that the alternative sunitinib administration
      schedule was significantly associated with maintaining 6W-RDI above 75% for RCC
      patients treated with sunitinib (OR 3.592, 95% CI 1.042-12.383, p = 0.043). On
      the other hand, there were no significant differences between 2 groups regarding
      occurrence rate of severe adverse events and prognosis by multivariate analysis.
      CONCLUSIONS: We report the results of an alternative medication schedule, the
      "weekday-on and weekend-off regimen", as a means of increasing 6W-RDI for
      metastatic RCC patients.

PMID- 30094692
TI  - Voltammetric aptasensor for thrombin by using a gold microelectrode modified with
      graphene oxide decorated with silver nanoparticles.
AB  - A sensitive electrochemical aptasensor was developed for the determination of
      thrombin. It is based on signal amplification by using graphene oxide (GO)
      decorated with silver nanoparticles (AgNP) and placed on a microelectrode. The
      graphene oxide decorated with silver nanoparticles (AgNP-GO) was synthesized by
      chemical reduction and then modified with a thrombin-binding aptamer 1 (TBA1; a
      29-mer) carrying a 3'-terminal thiol group. It was immobilized on the AgNP-GO by
      self-assembled monolayer technique to form the signaling probe (TBA1-AgNP-GO). A
      capture thrombin-binding aptamer 2 (TBA-2; a 15-mer) carrying a 3'-terminal thiol
      group was self-assembled onto the surface of the gold electrode. After binding of
      thrombin and the signaling probe, a sandwich of type TBA2-thrombin-TBA1-AgNP-GO
      is formed. The square wave voltammetric signal of the AgNP is then recorded. The
      electrochemical oxidation signal (measured at 0.21 V vs. Ag/AgCl) increases
      linearly with the concentration of thrombin in the range from 0.05 nmol.L-1 to 5
      nmol.L-1 with a detection limit of 0.03 nmol.L-1 (at S/N = 3). The aptasensor is
      highly specific and not affected by other proteins. It was successfully applied
      to the determination of thrombin in spiked human serum samples. Graphical
      abstract A sensitive electrochemical aptasensor for thrombin was developed based
      on the signal amplification of silver nanoparticles decorated graphene oxide at
      an ultramicroelectrode.

PMID- 30094694
TI  - Prognostic outcome and complications of sentinel lymph node navigation surgery
      for early-stage cervical cancer.
AB  - BACKGROUND: To evaluate the prognostic outcome and surgical complications in
      patients with early-stage cervical cancer who underwent sentinel node navigation
      surgery (SNNS) for hysterectomy or trachelectomy. METHODS: A total of 139
      patients who underwent SNNS using 99mTc phytate between 2009 and 2015 were
      evaluated. No further lymph node dissection was performed when intraoperative
      analysis of the sentinel lymph nodes (SLNs) was negative for metastasis. We
      compared the surgical complications between the SNNS group and 67 matched
      patients who underwent pelvic lymph node dissection (PLND) after SLN mapping
      between 2003 and 2008. We also examined the clinical outcomes in the SNNS group.
      RESULTS: The mean number of detected SLNs was 2.5 per patient. Fourteen of the
      139 patients in the SNNS group underwent PLND based on the intraoperative SLN
      results. The amount of blood loss, the operative time, and the number of
      perioperative complications were significantly less in the SNNS group than in the
      matched PLND group. There was no recurrence during a follow-up period ranging
      from 2 to 88 months (median 40 months) in the SNNS group. CONCLUSIONS: Using SNNS
      for early-stage cervical cancer is safe and effective and does not increase the
      recurrence rate. A future multicenter trial is warranted.

PMID- 30094696
TI  - Metachronous rectal metastasis from primary transverse colon cancer: a case
      report.
AB  - BACKGROUND: Colorectal metastases from primary colorectal cancers are very rare,
      and little is known about their epidemiological aspects or the best diagnostic
      and therapeutic strategies. Herein, we report a case of a 65-year-old woman with
      suspected metachronous metastasis to the rectum from primary transverse colon
      cancer. CASE PRESENTATION: The patient underwent a laparoscopic extended right
      hemicolectomy for primary transverse colon cancer. Histopathological examination
      showed moderately differentiated adenocarcinoma, and the tumor was diagnosed as
      stage IIA (T3, N0, M0). Fifteen months after her colectomy, a computed tomography
      scan demonstrated a rectal tumor and a right ovarian tumor. Colonoscopy revealed
      a superficial elevated lesion in the middle rectum, and histological analysis
      showed moderately differentiated adenocarcinoma. Laparoscopic low anterior
      resection preserving the left colic artery and bilateral adnexectomy were
      performed. Histological examination of the rectal tumor showed that
      adenocarcinoma was mainly present in the submucosa and muscularis propria, while
      the carcinoma-involved region of the mucosal layer had mucosal colonization
      representing the spread of metastatic tumor cells along the basement membrane of
      preexisting crypts and/or villi. The right ovarian tumor proved to be moderately
      differentiated adenocarcinoma that was positive for cytokeratin 20 and negative
      for cytokeratin 7 staining, indicating metastasis from the colorectal cancer. The
      rectal and ovarian tumors were similar to transverse colon cancer in
      architectural and cytological atypia. Both adenocarcinomas of the transverse
      colon and rectum were negative for p53 in immunohistochemical staining and RAS
      wild type in genetic assessment. These findings support a possible diagnosis of
      rectal and ovarian metastasis from the primary transverse colon cancer. The
      patient recovered well after surgery, and neither relapse nor metastasis was
      observed 18 months after surgery. CONCLUSION: Distinguishing primary from
      metastatic colorectal cancer can be challenging, but a comprehensive evaluation
      of histological features, clinical history, and tumor distribution can enable
      making a correct diagnosis and implementing optimal treatment.

PMID- 30094697
TI  - Examining grounded theory through the lens of rationalist epistemology.
AB  - The objective of scientific, or more broadly, academic knowledge is to provide an
      understanding of the social and natural world that lies beyond common sense and
      everyday thinking. Academics use an array of techniques, methods and conceptual
      apparatuses to achieve this goal. The question we explore in this essay is the
      following: Does the grounded theory approach, in the constructivist version
      developed by Kathy Charmaz, provide the necessary methodological tools for the
      creation of knowledge and theories beyond everyday thinking? To conduct our
      analysis, we have drawn on the rationalist epistemology originally developed by
      Gaston Bachelard and taken up a few decades later by Pierre Bourdieu and
      colleagues to look at the epistemological foundation of the CGT methods as
      defined by Charmaz. We focussed on two distinctive epistemological features
      characterising constructivist grounded theory (CGT): the use of inductive
      reasoning to generate interpretative theory; and the primacy of subjectivity over
      objectivity as the preferred path to knowledge making. While the usefulness of
      CGT for conducting qualitative research and understanding the perspective of
      social actors has been acknowledged by scholars in health professions education
      research and other research areas, the inductivist logic on which it draws raises
      questions concerning the nature of the knowledge yielded by this approach. As we
      argue in this article, it is still unclear in what way the interpretative theory
      generated by CGT is not a duplication of everyday thinking expressed through meta
      narratives. It is also unclear how the understanding of social phenomena can be
      refined if the use of inductive procedures logically implies the creation of a
      new theory each time a study is conducted. We engage with these questions to
      broaden the epistemological conversation within the health professions education
      research community. It is our hope that scholars in the field will engage in this
      epistemological conversation and advance it in new directions.

PMID- 30094698
TI  - Antibiotic Resistance Rates by Geographic Region Among Ocular Pathogens Collected
      During the ARMOR Surveillance Study.
AB  - INTRODUCTION: The Antibiotic Resistance Monitoring in Ocular micRoorganisms
      (ARMOR) study is an ongoing nationwide surveillance program that surveys in vitro
      antibiotic resistance rates and trends among ocular bacterial pathogens. We
      report resistance rates by geographic region for isolates collected from 2009
      through 2016. METHODS: Staphylococcus aureus, coagulase-negative staphylococci
      (CoNS), Streptococcus pneumoniae, Haemophilus influenzae, and Pseudomonas
      aeruginosa isolates from ocular infections were collected at clinical centers
      across the US and categorized by geographic region based on state. Minimum
      inhibitory concentrations (MICs) for various antibiotics were determined at a
      central laboratory, and isolates were classified as susceptible or resistant
      based on established breakpoints. Geographic differences in methicillin
      resistance among staphylococci were evaluated by chi2 test with multiple
      comparisons, whereas geographic differences in mean percentage antibiotic
      resistance were evaluated by one-way analyses of variance and Tukey's test.
      RESULTS: Overall, 4829 isolates (Midwest, 1886; West, 1167; Northeast, 1143;
      South, 633) were evaluated. Across all regions, azithromycin resistance was high
      among S. aureus (49.4-67.8%), CoNS (61.0-62.8%), and S. pneumoniae (22.3-48.7%),
      whereas fluoroquinolone resistance ranged from 26.1% to 47.8% among S. aureus and
      CoNS. Across all regions, all staphylococci were susceptible to vancomycin;
      besifloxacin MICs were similar to those of vancomycin. Geographic differences
      were observed for overall mean resistance among S. aureus, S. pneumoniae, and P.
      aeruginosa isolates (p <= 0.005); no regional differences were found among CoNS
      and H. influenzae isolates. Methicillin resistance in particular was higher among
      S. aureus isolates from the South and CoNS isolates from the Midwest (p <=
      0.006). CONCLUSION: This analysis of bacterial isolates from the ARMOR study
      demonstrated geographic variation in resistance rates among ocular isolates, with
      greater in vitro resistance apparent in the South and Midwest for some organisms.
      These data may inform clinicians in selecting appropriate treatment options for
      ocular infections. FUNDING: Bausch & Lomb, Inc.

PMID- 30094695
TI  - Correlates of Long-Term Opioid Abstinence After Randomization to Methadone Versus
      Buprenorphine/Naloxone in a Multi-Site Trial.
AB  - Opioid use disorder (OUD) is a chronic, relapsing condition with severe negative
      health consequences. Previous studies have reported that 5-year opioid abstinence
      is a good predictor of reduced likelihoods of relapse, but factors that shape
      long-term opioid abstinence are poorly understood. The present study is based on
      data from a prospective study of 699 adults with OUD who had been randomized to
      either methadone or buprenorphine/naloxone and who were followed for at least 5
      years. During the 5 years prior to the participants' last follow-up interview,
      232 (33.2%) had achieved 5-year abstinence from heroin. Of those 232, 145 (20.7%
      of the total) had remained abstinent from both heroin and other opioids (e.g.,
      hydrocodone, oxycodone, other opioid analgesics, excluding methadone or
      buprenorphine). Compared to non-abstinent individuals, those in both categories
      of opioid abstinence had lower problem severity in health and social functioning
      at the final follow-up. Logistic regression results indicated that cocaine users
      and injection drug users were less likely to achieve 5-year heroin abstinence,
      whereas Hispanics (vs. whites) and those treated in clinics on the West Coast
      (vs. East) were less likely to achieve 5-year abstinence from heroin and other
      opioids. For both abstinence category groups, abstinence was positively
      associated with older age at first opioid use, lower impulsivity, longer duration
      of treatment for OUD, and greater social support. Reducing cocaine use and
      injection drug use and increasing social support and retention in treatment may
      help maintain long-term abstinence from opioids among individuals treated with
      agonist pharmacotherapy.

PMID- 30094699
TI  - Injection of Onabotulinum Toxin A into the Bilateral External Oblique Muscle
      Attenuated Camptocormia: A Prospective Open-Label Study in Six Patients with
      Parkinson's Disease.
AB  - INTRODUCTION: Camptocormia (severe bending of the spine) is a debilitating
      complication of Parkinson's disease (PD) without established treatment. Botulinum
      toxin (BT) may be beneficial, but data is scarce regarding the efficacy of
      administration of BT into the bilateral external oblique (EO) muscle for
      treatment of camptocormia in PD. METHODS: Six patients with PD and camptocormia,
      with flexion of the thoracic spine, were enrolled in the study. BT (75 or 90
      units, onabotulinum toxin A) were injected into each EO bilaterally under
      sonographic guidance. Camptocormia angle (CA) was defined as the angle between
      the acromion-greater trochanter line and a vertical line. CA and disabling
      symptoms were evaluated during the treatment course. RESULTS: Two weeks after the
      injection of BT, the mean CA showed significant attenuation [median
      (interquartile range); 38 degrees  (23.5 degrees ) vs. 18 degrees  (21 degrees ),
      p = 0.028]. Subjective relief was present in cases 1-3 and 6, and absent in cases
      4 and 5. Cases 1-3 received repeated injections to maintain the amelioration; in
      cases 1 and 2, this was for 1 year or longer, while falls of case 3 limited the
      amelioration. CONCLUSION: Botulinum therapy into bilateral EO attenuated the
      angle of thoracic-level camptocormia in six patients with PD over the observation
      period of 2 weeks. The reproducibility of the results, long-term efficacy, and
      subjective relief of symptoms require further examination.

PMID- 30094702
TI  - Evaluation of 1294 Female Patients with Breast Pain: A Retrospective Study.
AB  - INTRODUCTION: Mastalgia, or breast pain, is one of the most important complaints
      referred to outpatient clinics. The objective of this study was to evaluate the
      factors causing mastalgia. All patients who presented to our clinic with
      complaints of mastalgia were assessed along with their type of mastalgia
      symptoms, menopausal status, and radiology results. METHODS: A total of 3157
      patients with mastalgia complaints visited our clinic between January 2015 and
      February 2018. Only 1294 of them were retrospectively screened. Age, sex,
      menopausal (premenopausal, postmenopausal) status, mastalgia type (cyclic, non
      cyclic), and imaging findings of the patients were examined. RESULTS: The mean
      age was 43.8 +/- 11.8 (13-86) years, with 453 (35%) patients younger than 40
      years and 841 (65%) older than 40. Cyclic mastalgia was found in 207 (16%)
      patients, and non-cyclic mastalgia was seen in 1087 (84%) patients. A total of
      786 (60.7%) patients were premenopausal, and 508 (39.3%) were postmenopausal.
      Mammography was used in 545 (42.1%) patients; 1190 (92.0%) women had breast
      ultrasonography. CONCLUSION: Although breast pain is a common symptom in women
      who are referred to breast outpatient clinics, we concluded that patients who
      complain of mastalgia should not be afraid of cancer. Despite this and for
      reassurance, clinical imaging may be necessary to alleviate these patients'
      suspicions.

PMID- 30094701
TI  - Communication With Children and Families About Disaster: Reviewing Multi
      disciplinary Literature 2015-2017.
AB  - PURPOSE OF REVIEW: To identify strategies for communicating with youth and
      children pre- and post-disaster in the context of a broader survey of child
      participation in disaster risk reduction as well as methods for communication
      with children. RECENT FINDINGS: Youth and children are capable of peer and
      community education and activism concerning disaster issues and such
      participation benefits the young actors. Family and sibling support are important
      in easing the impact of trauma on children. Contemporary forms of psychological
      first aid appear to do no harm and in line with current evidence. Generally, more
      evidence from evaluations is necessary to guide the development of communication
      strategies. Children are growing up in increasingly urban environments with less
      contact with nature and greater reliance on techno-social systems. Thus, young
      people may misunderstand natural hazards. Schools and conscious parenting can
      play important roles in building understanding and psychological resilience.

PMID- 30094700
TI  - Current Knowledge on Gene-Environment Interactions in Personality Disorders: an
      Update.
AB  - PURPOSE OF REVIEW: We review the existing literature on gene-environment
      interactions (G*E) and epigenetic changes primarily in borderline personality
      disorder (BPD) but also in antisocial, schizotypal, and avoidant personality
      disorders. RECENT FINDINGS: Research supports that susceptibility genes to BPD or
      its underlying traits may be expressed under certain environmental conditions
      such as physical or childhood sexual abuse. Epigenetic modifications of
      neurodevelopment- and stress-related genes are suggested to underlie the
      relationship between early life adversary and borderline personality disorder.
      Only limited studies have investigated the role of gene-environment interactions
      and epigenetic changes in the genesis of antisocial, schizotypal, and avoidant
      personality disorders. Considering the lack of pharmacological treatment for most
      personality disorders, the emerging evidence on the critical role of G*E and
      epigenetic changes in the genesis of personality disorders could help develop
      more biologically oriented therapeutic approaches. Future studies should explore
      the potential of this new therapeutic dimension.

PMID- 30094703
TI  - Disposition of ceftobiprole during continuous venous-venous hemodiafiltration
      (CVVHDF) in a single critically ill patient.

PMID- 30094704
TI  - Vomiting and constipation associated with tramadol and codeine: a comparative
      study in VigiBase(r).

PMID- 30094705
TI  - Identification and Field Evaluation of the Sex Pheromone of Orthaga achatina
      (Lepidoptera: Pyralidae).
AB  - Orthaga achatina (Lepidoptera: Pyralidae) is the most serious pest in south China
      of camphor trees, Cinnamomum camphora (L.) Presl, an important urban tree
      species. Gas chromatography-electroantennographic detection (GC-EAD) of the sex
      pheromone of O. achatina showed three EAD-active components. Coupled gas
      chromatography/mass spectrometry analyses identified these as (Z)-11-hexadecenol
      (Z11-16:OH), (Z)-11-hexadecenyl acetate (Z11-16:OAc), and (3Z,6Z,9Z,12Z,15Z)
      tricosapentaene (Z3,Z6,Z9,Z12,Z15-23:H). In field tests using different
      combinations of the three compounds, male moths were attracted to a mixture of
      Z11-16:OAc and Z3,Z6,Z9,Z12,Z15-23:H, but less attracted to other blends. Further
      field tests with different ratios of the two compounds determined the optimal
      ratio of the binary blend as 500:250. The addition of Z11-16:OH to Z11-16:OAc, or
      to the binary mixture of Z11-16: OAc and the pentaene did not yield higher
      catches. This shows that O. achatina uses a mixture of Type I and Type II sex
      pheromone components. Orthaga achatina is the third Pyraloidea species found to
      utilize Z3,Z6,Z9,Z12,Z15-23:H as a sex pheromone component.

PMID- 30094706
TI  - [Palliative therapy concepts for pancreatic carcinoma].
AB  - The majority of patients with ductal pancreatic adenocarcinoma are already in a
      locally advanced or metastatic stage at the time of diagnosis and require
      palliative therapy. Interventional and operative measures are available for the
      restoration of biliary outflow in bile duct obstruction and the continuity of the
      upper intestinal lumen in duodenal or gastric outlet obstruction. In the presence
      of tumor-related pain, pain therapy according to the World Health Organization
      (WHO) scheme or a truncus coeliacus blockade, in cachexia a nutritional therapy
      and in thromboembolic events an anticoagulant therapy are used. An individualized
      palliative chemotherapy regimen should be selected for each patient, taking into
      account the patient's general condition and the side effects profile of the
      chemotherapeutic agents. Radiochemotherapy and local ablative therapies should
      currently only be used within the framework of studies. A palliative resection is
      not recommended according to current knowledge.

PMID- 30094707
TI  - [Treatment approach for gall bladder and extrahepatic bile duct cancer].
AB  - BACKGROUND: Although the treatment and diagnostic regimens of gall bladder
      carcinoma and extrahepatic bile duct cancer have improved over the past years,
      the outcome and overall survival as prognostic values still remain poor. Early
      tumor stages of gall bladder carcinoma are the only exception. OBJECTIVE: This
      article focuses on the latest surgical therapy approaches including neoadjuvant,
      adjuvant and palliative therapy regimens. RESULTS: Neoadjuvant treatment concepts
      have so far been insufficiently evaluated and can therefore only be recommended
      within the framework of studies. In patients with primary resectable tumors there
      are so far no indications for improved results after neoadjuvant therapy. Radical
      R0 resection still remains the only curative treatment option; however, an
      advanced and inoperable stage is often already present at the time of diagnosis
      There are no uniform adjuvant treatment concepts and no standards evaluated by
      studies. Due to the currently available data, adjuvant radiochemotherapy and
      chemotherapy can also only be recommended within or as part of clinical trials.
      Palliative chemotherapy should only be used in advanced tumor stages and
      depending on the condition of the patient. CONCLUSION: To sustainably improve
      treatment strategies for advanced gall bladder carcinoma and extrahepatic bile
      duct cancer, uniform adjuvant as well as neoadjuvant therapy regimens need to be
      developed after evaluation in prospective randomized trials. This is the only way
      to improve the still poor prognosis of these tumor entities.

PMID- 30094708
TI  - Creatine Protects Against Cytosolic Calcium Dysregulation, Mitochondrial
      Depolarization and Increase of Reactive Oxygen Species Production in Rotenone
      Induced Cell Death of Cerebellar Granule Neurons.
AB  - Rotenone is a neurotoxin that is an active component of many pesticides which has
      been shown to induce Parkinsonism in animal models. We show that the cytotoxicity
      of exposure to nanomolar concentrations of rotenone in cultures of mature
      cerebellar granule neurons (CGN) in serum-free medium is not due to phagocytosis
      by glial contamination. A concentration as low as 5.65 +/- 0.51 nM of rotenone
      was enough to trigger 50% cell death of mature CGN in culture after 12 h. The
      addition of serum proteins to the culture medium attenuated rotenone
      neurotoxicity, and this can account at least in part for the requirement of
      higher rotenone concentrations to elicit neuronal cytotoxicity reported in
      previous works. Creatine partial protection against CGN death promoted by 5 nM
      rotenone correlated with creatine protection against rotenone-induced
      mitochondrial depolarization and oxidative stress. Furthermore, creatine largely
      attenuated the early dysregulation of cytosolic Ca2+ concentration after acute
      rotenone treatment. Noteworthy, our results also revealed that the sustained
      alteration of Ca2+ homeostasis induced by rotenone takes place at the onset of
      the enhancement of intracellular oxidative stress and before mitochondrial
      depolarization, pointing out that cytosolic Ca2+ dysregulation is a very early
      event in the rotenone toxicity to CGN.

PMID- 30094709
TI  - Diagnosis of Superficial Mycoses by a Rapid and Effective PCR Method from Samples
      of Scales, Nails and Hair.
AB  - Superficial mycoses are the most frequently diagnosed affections of the stratum
      corneum of the skin, nails and hair. It is generally caused by the presence of
      yeasts and dermatophytes. Onychomycosis is the most common infection with an
      incidence of 80-90% in Europe generally produced by Trichophyton rubrum. The aim
      of this study is to compare the traditional diagnostic techniques of superficial
      mycoses with a homemade and wide-spectrum fungal polymerase chain reaction (PCR)
      technique that amplifies a specific region of the 18S ribosomal RNA (rRNA)
      directly from samples of scales, nails and hair. A total of 626 clinical samples
      (obtained in the Basurto University Hospital, Bilbao, Spain) were analysed by
      traditional culture, microscopy and PCR. DNA extraction was carried out by using
      an extraction buffer and bovine serum, and amplification of samples and
      performance of the PCR were checked by conventional agarose gel electrophoresis
      with subsequent sequencing of amplified samples. A total of 211 samples (34%)
      resulted in positive diagnosis with at least one of the two applied methods:
      culture (21%) and PCR (22%). Despite the low percentage of identification
      achieved by the sequencing technique (40%), the value contributed by the
      amplification of the 18S region of the rRNA was considered important in the
      identification as it showed a high predictive values for both positive and
      negative diagnoses (90.9% and 94.6%, respectively). The proposed PCR method has
      been confirmed as a complementary, rapid, and effective method in the diagnosis
      of superficial mycoses. Additionally, it reduces the time to obtain satisfactory
      results from 4 weeks to 7 h.

PMID- 30094710
TI  - A reexamination on the deficiency of riboflavin accumulation in Malpighian
      tubules in larval translucent mutants of the silkworm, Bombyx mori.
AB  - A variety of insects accumulate high contents of riboflavin (vitamin B2) in their
      Malpighian tubules (MTs). Although this process is known to be genetically
      controlled, the mechanism is not known. In the 1940s and the 1950s, several
      studies showed that riboflavin contents were low in the MTs of some Bombyx mori
      (silkworm) mutants with translucent larval skin mutations (e.g., w-3, od, oa, and
      otm) and that genes responsible for these translucent mutations also affected
      riboflavin accumulation in the MTs. Since the 2000s, it has been shown that the w
      3 gene encodes an ABC transporter, whereas genes responsible for od, oa, and otm
      mutations encode for the biogenesis of lysosome-related organelles. These
      findings suggest that some genes of ABC transporters and biogenesis of lysosome
      related organelles may control the accumulation of riboflavin in MTs. Therefore,
      we reexamined the effects that translucent mutations have on the accumulation of
      riboflavin in MTs by using the translucent and wild-type segregants in mutant
      strains to measure the specific effect that each gene has on riboflavin
      accumulation (independent of genomic background). We used nine translucent
      mutations (w-3oe, oa, od, otm, Obs, oy, or, oh, and obt) even though the genes
      responsible for some of these mutations (Obs, oy, or, oh, and obt) have not yet
      been isolated. Through observation of larval MTs and measurements of riboflavin
      content using high-performance liquid chromatography, we found that the oa, od,
      otm, and or mutations were responsible for low contents of riboflavin in MTs,
      whereas the Obs and oy mutations did not affect riboflavin accumulation. This
      indicates that the molecular mechanism for riboflavin accumulation is similar but
      somewhat different than the mechanism responsible for uric acid accumulation in
      epidermal cells. We found that the genes responsible for oa, od, and otm
      mutations were consistent with those already established for uric acid
      accumulation in larval epidermis. This suggests that these three genes control
      riboflavin accumulation in MTs through a mechanism similar to that of uric acid
      accumulation, although we do not yet know why the or mutation also controls
      riboflavin accumulation.

PMID- 30094712
TI  - A Robust Statistical Approach to Analyse Population Pharmacokinetic Data in
      Critically Ill Patients Receiving Renal Replacement Therapy.
AB  - BACKGROUND AND AIM: Current approaches to antibiotic dose determination in
      critically ill patients requiring renal replacement therapy are primarily based
      on the assessment of highly heterogeneous data from small number of patients. The
      standard modelling approaches limit the scope of constructing robust confidence
      boundaries of the distribution of pharmacokinetics (PK) parameters, especially
      when the evaluation of possible association of demographic and clinical factors
      at different levels of the distribution of drug clearance is of interest.
      Commonly used compartmental models generally construct the inferences through a
      linear or non-linear mean regression, which is inadequate when the distribution
      is skewed, multi-modal or effected by atypical observation. In this study, we
      discuss the statistical challenges in robust estimation of the confidence
      boundaries of the PK parameters in the presence of highly heterogenous patient
      characteristics. METHODS: A novel stepwise approach to evaluate the confidence
      boundaries of PK parameters is proposed by combining PK modelling with mixed
      effects quantile regression (MEQR) methods. RESULTS: This method allows the
      assessment demographic and clinical factors' effects at any arbitrary quantiles
      of the outcome of interest, without restricting assumptions on the distributions.
      The MEQR approach allows us to investigate if the levels of association of the
      covariates are different at low, medium or high concentration. CONCLUSIONS: This
      methodological assessment is deemed as a background initial approach to support
      the development of a class of statistical algorithm in constructing robust
      confidence intervals of PK parameters which can be used for developing an
      optimised antibiotic dosing guideline for critically ill patients requiring renal
      replacement therapy.

PMID- 30094711
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Dabrafenib.
AB  - Dabrafenib is a potent and selective inhibitor of BRAF-mutant kinase that is
      approved, as monotherapy or in combination with trametinib (mitogen-activated
      protein kinase (MAPK) kinase (MEK) inhibitor), for unresectable or metastatic
      BRAF-mutated melanoma, advanced non-small cell lung cancer and anaplastic thyroid
      cancer harbouring the BRAFV600E mutation. The recommended dose of dabrafenib is
      150 mg twice daily (bid) under fasted conditions. After single oral
      administration of the recommended dose, the absolute oral bioavailability (F) of
      dabrafenib is 95%. Dabrafenib shows a time-dependent increase in apparent
      clearance (CL/F) following multiple doses, which is likely due to induction of
      its own metabolism through cytochrome P450 (CYP) 3A4. Therefore, steady state is
      reached only after 14 days of daily dose administration. Moreover, the extent of
      this auto-induction process is dependent on the dose, which explains why
      dabrafenib systemic exposure at steady state increases less than dose
      proportionally over the dose range of 75-300 mg bid. The main elimination route
      of dabrafenib is the oxidative metabolism via CYP3A4/2C8 and biliary excretion.
      Among the three major metabolites identified, hydroxy-dabrafenib appears to
      contribute to the pharmacological activity. Age, sex and body weight did not have
      any clinically significant influence on plasma exposure to dabrafenib. No dose
      adjustment is needed for patients with mild renal or hepatic impairment, whereas
      the impacts of severe impairment on dabrafenib pharmacokinetics remain unknown.
      Considering that dabrafenib is a substrate of CYP3A4/2C8 and is a CYP3A4/2B6/2C
      inducer, drug-drug interactions are expected with dabrafenib. The relationship
      between clinical outcomes and plasma exposure to dabrafenib and hydroxy
      dabrafenib should be investigated more deeply.

PMID- 30094713
TI  - Preventing incisional hernia: closing the midline laparotomy.

PMID- 30094714
TI  - Influence of increased letter spacing and font type on the reading ability of
      dyslexic children.
AB  - Recent research studies have shown that increased letter spacing has a positive
      effect on the reading ability of dyslexic individuals. This study aims to
      investigate the effect of spacing on the readability of different fonts for
      children with and without dyslexia. Results did not support the hypothesis of
      better performance among children with dyslexia when reading text in Dyslexie
      than in other fonts. They, however, revealed that only spacing plays a role in
      enhancing dyslexic individuals' reading performance because Dyslexie and the
      Times New Roman interspaced font have no difference. Furthermore, the negative
      effect of the unfriendly fonts Times New Roman Italic and Curlz MT was eliminated
      through increased interletter spacing.

PMID- 30094715
TI  - Adult perceptions of children with dyslexia in the USA.
AB  - This study examined adult perceptions of dyslexia among US adults. Participants
      (n = 623) answered survey questions pertaining to characteristics, views, and
      possible causes of DYS. Exploratory factor analysis revealed five distinct
      factors: (1) psychosocial causes, (2) external causes, (3) biological causes, (4)
      consequences, and (5) controllability. Three-way ANOVA's were conducted to
      determine the effects of ethnicity, gender, and parental status on how DYS was
      perceived. The results revealed ethnic, gender, and parental status differences.
      Males endorsed psychosocial causes and external causes more often than females.
      Those who self-identified as Asian viewed DYS as more controllable in comparison
      to Whites. Results also revealed a three-way interaction regarding
      controllability. Understanding the public's perceptions about developmental
      disorders helps distinguish true from erroneous beliefs, and understanding
      differences that may exist in particular groups can help implement targeted
      actions to improve awareness, care, and interventions for families.

PMID- 30094716
TI  - Inner retinal thickening in newly diagnosed choroidal neovascularization.
AB  - PURPOSE: Automated segmentation of retinal layers by spectral-domain optical
      coherence tomography (SD-OCT) is usually erroneous in the presence of retinal
      diseases. The purpose of this study is to report the changes in ganglion cell
      complex (GCC) comprising retina nerve fiber layer (RNFL), ganglion cell layer
      (GCL), and inner plexiform layer (IPL) in neovascular age-related macular
      degeneration (AMD) patients by manually correcting the automated segmentation
      errors. METHODS: Thirty eyes of 30 patients with new-onset choroidal
      neovascularization secondary to neovascular AMD and 30 eyes of 30 healthy
      subjects were included. The inner retinal thicknesses were measured using early
      treatment diabetic retinopathy circle in the central 1 mm (fovea) and surrounding
      3 mm diameter (parafovea) after checking the accuracy of automated segmentation
      lines. Manual segmentation was done to ensure the accurate segmentation, when
      needed. RESULTS: Neovascular AMD patients had thicker mean RNFL, GCL, IPL, and
      GCC thicknesses within the fovea compared to healthy eyes (p = 0.04, p = 0.001, p
      = 0.032, and p = 0.005, respectively). In the parafoveal area, among the
      thickness-related measurements, the only significant difference was a thicker
      mean RNFL (p = 0.002). CONCLUSION: Diffuse thickening of inner retinal layers in
      neovascular AMD may overestimate actual GCC thickness within fovea. This pseudo
      increase in GCC thickness and inner retinal layers in general likely does not
      reflect more cells or tissue, but rather diffuse edema which leads to a falsely
      increased reading of layer thickness. Such false readings may also make the
      assessment of other conditions that lead to reduced inner retinal layer thickness
      such as glaucoma, optic nerve disease, or retinovascular occlusions more
      difficult.

PMID- 30094717
TI  - Hospital volume in ureterorenoscopic stone treatment: 99 operations per year
      could increase the chance of a better outcome-results of the German prospective
      multicentre BUSTER project.
AB  - BACKGROUND: Despite the high utilisation of ureterorenoscopy (URS) in
      interventional stone treatment, there is little evidence of any link between
      annual hospital volume and outcome. METHODS: From January to April 2015, data
      from 307 URS patients were prospectively recorded in the multicentre
      observational BUSTER-Trial (Benchmarks of ureterorenoscopic stone treatment
      results in terms of complications, quality of life, and stone-free rates). The
      best threshold value for annual hospital volume with an independent effect on the
      outcome (measured on stone-free and complication rates) of our study group was
      established with logistic regression. RESULTS: In 38.4% of cases of renal and
      61.6% of ureteral stones, median stone size was 6 mm with an interquartile range
      (IQR) of 4-8 mm. The annual URS rate in the 14 participating hospitals ranged
      from 77 to 333 (median 144; IQR 109-208). The binary endpoint as a combination of
      completely stone-free or residual fragments small enough to pass spontaneously
      and a maximum complication severity of Clavien-Dindo grade 1 was attained in
      234/252 (92.9%) cases with a hospital volume of >= 99 URS compared with 43/55
      (78.2%) in < 99 URS (p = 0.002). Adjusted for patient-, stone- and physician
      related factors, an annual hospital URS volume of >= 99 increases the chance of
      an optimum outcome (OR = 3.92; 95% CI 1.46-10.51; p = 0.007). CONCLUSIONS: An
      independent effect of URS hospital volume on outcome quality in the 14
      participating hospitals was demonstrated. Threshold values for annual case
      numbers should be scientifically established irrespective of the considered
      procedure.

PMID- 30094718
TI  - Feasibility of dose escalation using intraoperative radiotherapy following
      resection of large brain metastases compared to post-operative stereotactic
      radiosurgery.
AB  - BACKGROUND AND PURPOSE: Post-operative SRS (stereotactic radiosurgery) for large
      brain metastases is challenged by risks of radiation necrosis that limit SRS
      dose. Intraoperative radiotherapy (IORT) is a potential alternative, however
      standard dose recommendations are lacking. METHODS AND MATERIALS: Twenty
      consecutive brain metastases treated with post-operative SRS were retrospectively
      compared to IORT plans generated for 10-30 Gy in 1 fraction to 0-5 mm by
      estimating the applicator size and distance from critical organs using pre
      operative and post-operative MRI. Additionally, 7 consecutive patients treated
      with IORT 30 Gy to surface were compared to retrospectively generated SRS plans
      using the post-operative MRI to 15-20 Gy and 30 Gy in 1 fraction marginal dose.
      RESULTS: For the 20 resection cavities treated with SRS and retrospectively
      compared to IORT, IORT from 10 to 30Gy resulted in lower or not significantly
      different doses to the optic apparatus and brainstem. Comparatively for the 7
      patients treated with IORT 30 Gy to retrospective SRS plans to standard 15-20 Gy
      and 30 Gy marginal dose, IORT resulted in significantly lower doses to the optic
      apparatus and brainstem. At a median follow-up of 6.2 months, 86% of patients
      treated with surgery and IORT achieved local control and 0% developed
      radiographic or symptomatic radiation necrosis. CONCLUSIONS: Critical organ
      dosimetry for IORT remains generally lower than that achieved with single
      fraction SRS following resection of large brain metastases. We recommend 30 Gy to
      surface as the preferred prescription, consistent with the dose recommendation
      for IORT in glioblastoma used in the ongoing INTRAGO-II phase-III trial. Early
      clinical outcomes appear promising for surgery and IORT.

PMID- 30094719
TI  - Oscillatory brain activity associates with neuroligin-3 expression and predicts
      progression free survival in patients with diffuse glioma.
AB  - INTRODUCTION: Diffuse gliomas have local and global effects on neurophysiological
      brain functioning, which are often seen as 'passive' consequences of the tumor.
      However, seminal preclinical work has shown a prominent role for neuronal
      activity in glioma growth: mediated by neuroligin-3 (NLGN3), increased neuronal
      activity causes faster glioma growth. It is unclear whether the same holds true
      in patients. Here, we investigate whether lower levels of oscillatory brain
      activity relate to lower NLGN3 expression and predict longer progression free
      survival (PFS) in diffuse glioma patients. METHODS: Twenty-four newly diagnosed
      patients with diffuse glioma underwent magnetoencephalography and subsequent
      tumor resection. Oscillatory brain activity was approximated by calculating
      broadband power (0.5-48 Hz) of the magnetoencephalography. NLGN3 expression in
      glioma tissue was semi-quantitatively assessed by immunohistochemistry. Peritumor
      and global oscillatory brain activity was then compared between different levels
      of NLGN3 expression with Kruskal-Wallis tests. Cox proportional hazards analyses
      were performed to estimate the predictive value of oscillatory brain activity for
      PFS. RESULTS: Patients with low expression of NLGN3 had lower levels of global
      oscillatory brain activity than patients with higher NLGN3 expression (P <
      0.001). Moreover, lower peritumor (hazard ratio 2.17, P = 0.008) and global
      oscillatory brain activity (hazard ratio 2.10, P = 0.008) predicted longer PFS.
      CONCLUSIONS: Lower levels of peritumor and global oscillatory brain activity are
      related to lower NLGN3 expression and longer PFS, corroborating preclinical
      research. This study highlights the important interplay between macroscopically
      measured brain activity and glioma progression, and may lead to new therapeutic
      interventions in diffuse glioma patients.

PMID- 30094721
TI  - Preparation of Sustained Release Tablet with Minimized Usage of Glyceryl Behenate
      Using Post-Heating Method.
AB  - The purpose of this study was to prepare sustained release (SR) matrix tablets
      using a direct compression incorporated with a post-heating process. Allopurinol
      was selected due to the water-soluble property and Compritol 888 ATO(r) (also
      known as glyceryl behenate) was used as an SR matrix-forming agent. The API, SR
      material, microcrystalline cellulose, and magnesium stearate (lubricant) were
      mixed and prepared into a tablet by a direct compression method. The compressed
      tablets were stored in a dry oven at four temperatures (60, 70, 80, and 90
      degrees C) and for three time periods (15, 30, 45 min). The DSC and PXRD data
      indicated that the crystallinity of the API was not altered by the post-heating
      method. However, SEM images demonstrated that Compritol 888 ATO(r) was melted by
      the post-heating method, and that the melted Compritol 888 ATO(r) could form a
      strong matrix. This strong matrix led to the significant sustained release
      behavior of hydrophilic APIs. As little as 3 mg of Compritol 888 ATO(r) (0.65% of
      total tablet weight), when heated at 80 degrees C for 15 min, showed sustained
      release over 10 h. The post-heating method exerted a significant influence on
      lipid-based matrix tablets and allowed a reduction in the amount of material
      required for a water-soluble drug. This will also provide a valuable insight into
      lipid-based SR tablets and will allow their application to higher quality
      products and easier processing procedures.

PMID- 30094722
TI  - Lacidipine Amorphous Solid Dispersion Based on Hot Melt Extrusion: Good
      Miscibility, Enhanced Dissolution, and Favorable Stability.
AB  - The present study aimed to increase the in vitro dissolution rate of lacidipine,
      a poorly water-soluble drug, by formulating amorphous solid dispersions (ASDs)
      using hot-melt extrusion (HME). Differential scanning calorimetry, powder X-ray
      diffraction, polarized light microscopy, and Fourier transform infrared were used
      to characterize the optimal formulations and evaluate the physical stability for
      the stress test. Film-casting method and hot-stage microscopy were applied to
      study the miscibility of lacidipine and the drug carriers. In vitro dissolution
      tests were conducted as the final evaluation index. The optimal formulations were
      successfully obtained with Soluplus and PVP VA64 at a drug/carrier ratio of 1:10
      (w/w), Fourier transform infrared studies revealed the hydrogen bonding between
      drug and polymers, and in vitro dissolution rates of the optimal formulations
      were extremely enhanced compared to bulk lacidipine and physical mixtures,
      similar with that of the commercial tablet. The ASD formulated with Soluplus
      showed better physical stability than that with PVP VA64. A strong hydrogen
      bonding and good drug-polymer miscibility were essential to hinder the
      recrystallization of lacidipine ASDs. In conclusion, the lacidipine ASD
      formulated with Soluplus showed a significant increase in in vitro dissolution
      rate and favorable physical stability in the stress test.

PMID- 30094724
TI  - Feasibility of Implementing Community Partnerships to Provide Diabetes Prevention
      Services to Youth.
AB  - Type 2 diabetes (T2D) in youth has increased as a result of the obesity epidemic.
      Diabetes prevention programming is needed for youth, at risk for T2D, and their
      families. However, there is a lack of diabetes prevention services for this
      population. There is evidence for the benefit of lifestyle modification for
      decreasing diabetes risk, however there are barriers for youth to access these
      services in a traditional clinical setting. Our Youth Diabetes Prevention Clinic
      (YDPC) created partnerships within the community to increase access to diabetes
      prevention services for at risk youth. YDPC personnel approached community
      organizations who had the expertise and capacity to partner in needed areas.
      These partnerships allowed for the development and facilitation of a community
      based diabetes prevention group. Youth and their families participated in a 12
      week diabetes prevention group. We measured attendance and participant
      satisfaction with the program. Families attended an average of 5.1 sessions from
      January to October 2016. Participant satisfaction was collected five times.
      Physical activity was rated as "awesome" or "good" by 88% of the respondents. The
      nutrition activities were rated as "awesome" or "good" by 97% of respondents.
      Physicians and families express a desire for diabetes prevention services,
      however barriers make it difficult for families to fully participate. Creating
      partnerships within the community allows for increased access to diabetes
      prevention services for high-risk, underserved families.

PMID- 30094723
TI  - Social Determinants of Sexual Behavior and Awareness of Sexually Transmitted
      Infections (STI) Among Low-Income HIV+ or STI At-Risk Hispanic Residents
      Receiving Care at the U.S.-Mexico Border.
AB  - U.S.-Mexico border communities are uniquely vulnerable to sexually transmitted
      infection (STI) transmission given the economic and social challenges these
      communities face. This study examines how marginalized statuses of U.S. border
      residents are associated with STI awareness and sexual behaviors. We surveyed low
      income residents receiving STI testing and/or HIV/AIDS care in the lower Rio
      Grande Valley of southernmost Texas. Respondents aged 18+ took a self
      administered survey available in English or Spanish in a clinic waiting room (N =
      282). Approximately 52% of respondents reported being HIV+, and 32% of
      respondents reported having a prior STI other than HIV. Although most respondents
      had heard of HPV (72%), awareness of the HPV vaccine was low across all subgroups
      (28%), including women (< 35%), reflecting previous findings that border
      residents are less knowledgeable about the HPV vaccine. Almost half of
      respondents reported always using a condom (45%), which is higher than elsewhere
      in the U.S. Male and non-Hispanic respondents had higher estimated prevalence
      ratios (PR) of lifetime partners [PR 1.39 (95% confidence interval 1.43-3.68), PR
      1.88 (1.04-3.41), respectively] and sexual partners met online [PR 3.73 (1.00
      14.06), PR 19.98 (5.70-70.10), respectively]. Sexual minority, non-Hispanic, and
      male respondents had higher adjusted odds ratios (AOR) of utilizing the internet
      to find sexual partners than their peers [AOR 2.45 (1.60-3.87), AOR 1.52 (1.11
      2.07), AOR 1.97 (1.20-3.24), respectively], placing them at greater STI
      transmission risk. We found diversity in dimensions of STI awareness and sexual
      behaviors in our sample. Results can help tailor public health interventions to
      the unique STI risks of marginalized groups in border communities.

PMID- 30094720
TI  - Expression of LC3B and FIP200/Atg17 in brain metastases of breast cancer.
AB  - BACKGROUND: Macroautophagy/autophagy is considered to play key roles in tumor
      cell evasion of therapy and establishment of metastases in breast cancer. High
      expression of LC3, a residual autophagy marker, in primary breast tumors has been
      associated with metastatic disease and poor outcome. FIP200/Atg17, a multi
      functional pro-survival molecule required for autophagy, has been implicated in
      brain metastases in experimental models. However, expression of these proteins
      has not been examined in brain metastases from patients with breast cancer.
      METHODS: In this retrospective study, specimens from 44 patients with brain
      metastases of infiltrating ductal carcinoma of the breast (IDC), unpaired samples
      from 52 patients with primary IDC (primary-BC) and 16 matched-paired samples were
      analyzed for LC3 puncta, expression of FIP200/Atg17, and p62 staining. RESULTS:
      LC3-puncta+ tumor cells and FIP200/Atg17 expression were detected in greater than
      90% of brain metastases but there were considerable intra- and inter-tumor
      differences in expression levels. High numbers of LC3-puncta+ tumor cells in
      brain metastases correlated with a significantly shorter survival time in triple
      negative breast cancer. FIP200/Atg17 protein levels were significantly higher in
      metastases that subsequently recurred following therapy. The percentages of LC3
      puncta+ tumor cells and FIP200/Atg17 protein expression levels, but not mRNA
      levels, were significantly higher in metastases than primary-BC. Meta-analysis of
      gene expression datasets revealed a significant correlation between higher
      FIP200(RB1CC1)/Atg17 mRNA levels in primary-BC tumors and shorter disease-free
      survival. CONCLUSIONS: These results support assessments of precision medicine
      guided targeting of autophagy in treatment of brain metastases in breast cancer
      patients.

PMID- 30094726
TI  - Emergence of polarized opinions from free association networks.
AB  - We developed a method that can identify polarized public opinions by finding
      modules in a network of statistically related free word associations.
      Associations to the cue "migrant" were collected from two independent and
      comprehensive samples in Hungary (N1 = 505, N2 = 505). The co-occurrence-based
      relations of the free word associations reflected emotional similarity, and the
      modules of the association network were validated with well-established measures.
      The positive pole of the associations was gathered around the concept of
      "Refugees" who need help, whereas the negative pole associated asylum seekers
      with "Violence." The results were relatively consistent in the two independent
      samples. We demonstrated that analyzing the modular organization of association
      networks can be a tool for identifying the most important dimensions of public
      opinion about a relevant social issue without using predefined constructs.

PMID- 30094725
TI  - Effect of vildagliptin versus glibenclamide on endothelial function and arterial
      stiffness in patients with type 2 diabetes and hypertension: a randomized
      controlled trial.
AB  - AIMS: Several trials have reported that dipeptidyl peptidase-4 (DPP-4)
      inhibitors, used to treat type 2 diabetes (T2DM), improve endothelial function.
      The current study investigated the effects of vildagliptin, a DPP-4 inhibitor,
      compared to glibenclamide on endothelial function, arterial stiffness, and blood
      pressure in patients with T2DM and hypertension. METHODS: Patients aged over 35
      years with T2DM and hypertension, but without cardiovascular disease, were
      randomly allocated to treatment with vildagliptin (n = 25) or glibenclamide (n =
      25). Both groups took metformin. Endothelial function was evaluated by peripheral
      artery tonometry (Endo-PAT 2000) to calculate the reactive hyperemia index (RHI)
      and arterial stiffness. Primary outcome was change in the RHI after 12 weeks of
      treatment. Twenty-four-hour non-invasive ambulatory blood pressure monitoring was
      performed using a Mobil-O-Graph(r) 24-h PWA monitor. Arterial stiffness was
      assessed using the augmentation index corrected for 75 bpm (AIx75), pulse wave
      velocity (PWV) and central systolic blood pressure (cSBP). RESULTS: There were no
      changes in the RHI in the vildagliptin group (before 2.35 +/- 0.59; after 2.24 +/
      0.60; p value = NS) or in the glibenclamide group (before 2.36 +/- 0.52; after
      2.34 +/- 0.50; p value = NS), with no differences between groups (p value = NS).
      There was also no difference between vildagliptin and glibenclamide treatment in
      respect to AIx75 (p value = NS), cSBP (p value = NS) or PWV (p value = NS).
      CONCLUSIONS: Vildagliptin and glibenclamide similarly do not change the
      endothelial function and arterial stiffness after 12 weeks of treatment in
      diabetic and hypertensive patients without cardiovascular disease. Thus,
      vildagliptin has a neutral effect on vascular function. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT02145611, registered on 11 Jun 2013.

PMID- 30094728
TI  - Physical activity and associations with treatment-induced adverse effects among
      prostate cancer patients.
AB  - PURPOSE: The present study aimed to determine the level of physical activity (PA)
      among prostate cancer (PCa) patients across treatment modalities and explore the
      association between PA and treatment-induced adverse effects (AEs). METHODS: The
      present study was based on a cross-sectional postal survey among members of the
      Norwegian Prostate Cancer Association. Patients were eligible for the present
      study if they had either (1) completed radical prostatectomy, (2) completed
      radiotherapy and (neo)-adjuvant androgen deprivation therapy (ADT), or (3) were
      undergoing lifelong ADT. Adverse effects were measured by the Expanded Prostate
      Cancer Index Composite for Clinical Practice. RESULTS: In total, 696 patients
      were included. There was no statistically significant difference in level of PA
      across treatment modalities. Bowel symptoms mainly related to radiotherapy
      decreased the odds of exercising >= 2 times per week, along with age >= 70 years,
      participation in the workforce, and BMI >= 25 kg/m2. Among patients who were
      undergoing ADT, 5 years or more since diagnosis reduced the odds of exercising >=
      2 times per week by almost 60%. CONCLUSION: The level of PA did not differ across
      PCa patients treated with different modalities. Increasing bowel symptoms reduced
      the likelihood of exercising >= 2 times per week. PCa patients should be educated
      about possible treatment-induced AEs affecting PA level, enabling them to
      counteract the development of physical inactivity.

PMID- 30094727
TI  - Yak and Tibetan sheep trampling inhibit reproductive and photosynthetic traits of
      Medicago ruthenica var. inschanica.
AB  - Livestock grazing affects grassland stability, resilience, and productivity owing
      to trampling, foraging, and excretion. Over time, trampling influences a wide
      range of grassland components and can have lasting effects. Trampling helps
      maintain grassland health but may also cause its degradation. In a field
      experiment over two growing seasons, we simulated yak and sheep trampling at
      different intensities and investigated their effects on the reproductive and
      photosynthetic characteristics of Medicago ruthenica var. inschanica in a Tianzhu
      alpine meadow in Gansu Province, China. Our results show that simulated trampling
      inhibited the asexual and sexual reproduction and growth of M. ruthenica. The
      root surface area, root volume, root biomass, pod length, pod number per unit
      area, number of seeds per pod, thousand-seed weight, and seed yield were
      significantly reduced under simulated trampling in the upper 30 cm of soil (P <
      0.05) but were not reduced in the deeper soil layers (> 30 cm). Light trampling
      by both yak and Tibetan sheep promoted photosynthesis, while heavy trampling by
      both species inhibited photosynthesis. Yak trampling inhibited photosynthesis
      more than Tibetan sheep trampling, and overall, the adverse effects of yak
      trampling on asexual and sexual reproduction and growth of M. ruthenica were
      greater than those of Tibetan sheep trampling. Thus, the effect of yak trampling
      is greater than the effect of trampling by Tibetan sheep, where the different
      trampling intensities of yak and Tibetan sheep can result in direct but varied
      influences on grasslands, potentially leading to grassland differentiation.

PMID- 30094729
TI  - Emotional distress and unmet supportive care needs in survivors of breast cancer
      beyond the end of primary treatment.
AB  - PURPOSE: Cancer patient survival rates are rapidly growing, and further data are
      needed on the impact of the disease beyond diagnosis and treatment phases. The
      aims of this study were to analyze the prevalence and sociodemographic and
      medical risk factors of clinical distress. Additionally, we also explore the
      relationship between unmet psychosocial needs and both clinical distress and
      subgroups of survival periods. METHODS: A cross-sectional study of 450 women who
      at least 1 month before had completed the primary treatment for breast cancer was
      conducted. The Brief Symptom Inventory 18 and the Cancer Survivors Unmet Needs
      measure were used. RESULTS: One in four women showed clinical distress related to
      unmet psychosocial needs. None of the sociodemographic and medical predictors was
      associated with clinical distress. Needs focused on the possibility of recurrence
      and its cognitive-emotional impact were the most frequent. Needs tended to
      decrease through periods of survival; however, there was a considerable level of
      unmet needs even among long-term survivors. CONCLUSIONS: The findings highlight
      the relevance of extending psychosocial care beyond the breast cancer primary
      medical treatment. Early and regular screen for distress and unmet supportive
      needs permits to identify high-risk groups that likely benefit from targeted
      preventive interventions.

PMID- 30094730
TI  - Safety and feasibility of electrical muscle stimulation in patients undergoing
      autologous and allogeneic stem cell transplantation or intensive chemotherapy.
AB  - : Intensive chemotherapy, with or without following autologous or allogeneic stem
      cell transplantation (HSCT), is often the only curative treatment option for
      patients with hematological malignancies and leave many survivors physically and
      psychologically impaired. Electrical muscle stimulation (EMS) is a proven tool to
      improve physical performance in seniors and patients with chronic diseases. We
      therefore investigated the safety and feasibility of EMS in 45 patients
      undergoing autologous HSCT (n = 13), allogeneic HSCT (n = 11) and intensive
      chemotherapy (n = 21). Furthermore, physical (assessed by 6-min walking distance
      (6MWD) and short physical performance battery (SPPB)) and psychological
      performance (assessed by multidimensional fatigue inventory (MFI) and the EORTC
      QOL-C30 questionnaire) were measured before chemotherapy (T1) and at discharge
      from hospital (T2). Four patients died due to septic shock, two withdrew consent
      before the start of EMS training and five stopped EMS training during the study
      because of chemotherapy-related complications, loss of motivation or loss of
      ability to use EMS autonomously. Thirty-four out of 45 (76%) patients used EMS
      throughout the study period and participated in physical and psychological tests
      at time points 1 and 2. EMS-related adverse events were hematoma (n = 1) and
      muscle pain (n = 2). No bleeding events > 1 according to the WHO bleeding scale
      occurred. Decline in 6MWD from T1 to T2 was 24 m. The SPPB score stayed the same
      with 11 points at T1 and T2. Most MFI subscales showed stable fatigue levels and
      quality of life (QoL) did not decrease significantly throughout therapy. EMS is
      feasible and safe in patients undergoing intensive chemotherapy. TRIAL
      REGISTRATION: NCT03467087.

PMID- 30094731
TI  - Concept domain validation and item generation for the Treatment-Induced
      Neuropathy Assessment Scale (TNAS).
AB  - PURPOSE: Treatment-induced peripheral neuropathy (TIPN) is a difficult problem
      experienced by patients with cancer that can interfere with their ability to
      receive optimal therapy. The Treatment-Induced Peripheral Neuropathy Scale (TNAS)
      is a patient-reported outcome (PRO) measure developed to assess TIPN symptom
      burden. However, PRO validation is an ongoing process. The aim of this
      qualitative study was to define the conceptual model, establish content domain
      validity, and refine items for the TNAS based on patient input. METHODS: Patients
      who received bortezomib, oxaliplatin, or platinum-taxane combination therapy
      reported their experience of TIPN in single qualitative audiotaped interviews.
      Themes of the TIPN experience were identified by descriptive analysis of the
      transcribed interviews. RESULTS: Three groups of 10 patients each who had
      received bortezomib, oxaliplatin, or platinum-taxane combination therapy, for a
      total of 30 patients, reported their experiences. Two themes reported by patients
      were TIPN sensations and functional interference. Five sensations (numbness,
      tingling, pain, heat or burning, and coldness) and five functional impacts (using
      hands, walking, maintaining balance or falling, wearing shoes, and sleeping) were
      reported by at least 20% of patients and were selected for inclusion in the TNAS
      v3.0 for additional psychometric testing. CONCLUSIONS: The assessment of TIPN
      must be convenient, reliable, and practical for patients, who are the most
      reliable source of information about symptoms. The TNAS, developed with direct
      patient input, provides an easily administered and conceptually valid method of
      patient report of TIPN burden for use in research and practice.

PMID- 30094732
TI  - Risk factors associated with chemotherapy-induced nausea and vomiting in the
      triplet antiemetic regimen including palonosetron or granisetron for cisplatin
      based chemotherapy: analysis of a randomized, double-blind controlled trial.
AB  - PURPOSE: The triplet antiemetic regimen is recommended for cisplatin-based highly
      emetogenic chemotherapy, in the current guidelines for antiemetic prophylaxis.
      Although risk factors related to chemotherapy-induced nausea and vomiting (CINV)
      have been identified by several prior studies, there are only few studies
      evaluating risk factors associated with the prophylactic triplet antiemetic
      therapy, particularly in palonosetron use. The present study aimed to reveal the
      risk factors related to CINV development in patients receiving cisplatin and to
      compare CINV risk factors between palonosetron and granisetron use. METHODS: In
      total, 825 patients in a phase III trial receiving palonosetron with graniestron
      were evaluated. Multivariate logistic regression models were used to predict risk
      factors associated with CINV development. Additionally, risk factors associated
      with CINV development were separately evaluated in each treatment group. RESULTS:
      Multivariate analysis of the entire study group revealed that sex, age, cisplatin
      dose, and granisetron use were significant and independent factors affecting CINV
      development in the overall phase. Similarly, sex and age were risk factors for
      CINV in both treatment groups. Kaplan-Meier curves classified by each treatment
      group showed no significant difference between the groups among patients without
      any risk factors for CINV (P = 0.353). Conversely, complete response rates for
      patients with at least one risk factor were higher in patients receiving
      palonosetron (P = 0.049). CONCLUSIONS: This analysis revealed the importance of
      previously reported CINV risk factors when using triplet antiemetics.
      Palonosetron might be preferred for patients with at least one risk factor.

PMID- 30094733
TI  - Palliative sedation in clinical scenarios: results of a modified Delphi study.
AB  - PURPOSE: To explore the consistency in international expert opinions about
      palliative sedation. METHODS: A modified electronic-Delphi procedure was carried
      out in two rounds. On hundred nine eligible experts were identified from their
      publications in MEDLINE related with terminal delirium, dyspnea and palliative
      sedation in the last 3 years. Delphi study included three vignettes of cancer
      patients and two non-cancer patients, with an estimated survival of days and
      severe suffering secondary to refractory complications. Experts were asked about
      whether they would perform continuous sedation and sedation level (described as
      Richmond Agitation Sedation Scale or defined as patient/family report of symptom
      relief). Consensus was considered when 70% or more of the experts agreed on a
      certain topic. RESULTS: Thirty-four and 27 panellists completed the 2 Delphi
      rounds, respectively. Participants were from the USA, Canada, Europe, Australia
      and Asia. One hundred per cent, 97% and 88% of the respondent agreed use of
      sedatives, continuously or temporary, in cases of refractory delirium, dyspnea
      secondary to lung cancer and GOLD IV-EPOC. There were discrepancies for cases of
      dementia and psycho-existential suffering. Expert selection of continuous
      palliative sedation was 93% for delirium, 41% for cancer dyspnea, 66% for EPOC
      dyspnea, 22% for agitation/pain in dementia and 19% for existential suffering.
      Responses about types and levels of sedation did not achieve consensus in any
      cases. CONCLUSIONS: The Delphi study failed to reach consensus in continuous
      palliative sedation and sedation levels for patients with refractory symptoms
      described in hypothetical clinical scenarios.

PMID- 30094734
TI  - Large-Scale EGFR Mutation Testing in Clinical Practice: Analysis of a Series of
      18,920 Non-Small Cell Lung Cancer Cases.
AB  - We make use of a very large dataset of non-small cell lung cancer specimens to
      examine the molecular epidemiology of EGFR mutations, particularly with respect
      to rare and compound mutations, and to non-adenocarcinoma histological subtypes.
      We also demonstrate the feasibility of large-scale EGFR mutation screening using
      the full range of specimens encountered in routine practice. We retrospectively
      reviewed 18,920 unselected EGFR mutation results from our centre between July
      2009 and October 2016, using Qiagen's therascreen EGFR RGQ PCR Kit. Mutation
      rates were correlated with patient demographics and tumour histology. Our testing
      success rate was 93.9%, with similar success rates using histological and
      cytological specimens. Rare, potentially-targetable mutations accounted for 9.5%
      of all mutations detected. We identified a 2.5% mutation rate in tumours
      diagnosed as squamous cell carcinomas. There was a trend towards increasing EGFR
      mutation rates with increasing age, and while Del19 was the commonest mutation in
      the young, L858R predominated in the elderly. We found that EGFR mutation
      heterogeneity is rare within tumours and between primary and metastatic deposits.
      Our data demonstrate that large-scale, reflex EGFR mutation testing is feasible
      and affordable in the context of a publicly-funded health system. Furthermore, we
      have shown that the use of techniques sensitive only to classical mutations and
      selection of patients on the grounds of age, sex and histology denies patients
      access to potentially beneficial TKI therapy.

PMID- 30094735
TI  - The Psychiatrist Writing for Popular Media.

PMID- 30094736
TI  - 'It's Like You Do It Without Knowing That You're Doing It': Practitioner
      Experiences with ACT Implementation.
AB  - Using a case study approach, this study explores the experiences of providers at
      three organizations identified by county mental health executives as exemplar
      programs that have received continued and competitive funding to deliver
      assertive community treatment (ACT) in a large urban county in California.
      Interviews were conducted with 37 participants including program directors (n =
      4), frontline staff (n = 31), and county mental health executives (n = 2).
      Frontline provider perspectives reveal that, in many ways, teams appear to be
      working within an ACT model in the absence of detailed explicit knowledge about
      ACT's core components, frequent or in-depth conversations about ACT, or awareness
      of fidelity monitoring. Integration of program director and county executive
      perspectives illustrates how inner and outer contextual information can explain
      these on-the-ground ACT implementation experiences. This study illustrates the
      nuanced ways that frontline staff might understand and define evidence-based
      practice (EBP) use and has implications for studying EBP implementation.

PMID- 30094737
TI  - An Academic and Practice Partnership to Assess the Behavioral Health Needs of
      Nebraska.
AB  - Schools of Public Health have a commitment to engage in practice-based research
      and be involved in collaborative partnerships. In 2016 the faculty, staff, and
      students from the University of Nebraska Medical Center College of Public Health
      and the Nebraska Department of Health and Human Services, Division of Behavioral
      Health collaborated to develop and administer a comprehensive assessment of the
      mental health and substance use disorder services provided by the Division of
      Behavioral Health. The purpose of this paper is to describe the process used to
      develop the trusting and mutually beneficial partnership and the data tools that
      were created and used to assess and determine the behavioral health needs. It is
      unrealistic to think that practitioners could undertake a project of this
      magnitude on their own. It is essential to have identified processes and systems
      in place for others to follow.

PMID- 30094738
TI  - Factors Associated with Rapid Readmission Among Nevada State Psychiatric Hospital
      Patients.
AB  - Rapid readmission (RR) of psychiatric patients within 30 days of discharge places
      a costly burden on state psychiatric facilities and may indicate suboptimal
      service provisions. Information regarding variables associated with RR of
      psychiatric patients is limited, particularly in Nevada. This study attempts to
      identify factors associated with RR at a Nevada state psychiatric hospital.
      Participants included 7177 patients admitted between May 2012 and April 2014.
      Using logistic regression, all admissions were reviewed and rapid readmits
      compared to counterparts who were not readmitted within 30 days. Nevada suffers
      from budget cuts in mental health care spending because of recent economic crisis
      and severe lack of bed space. This study demonstrates that it may be possible to
      reduce rates of costly RR by focusing on those with a history of RR and
      modifiable factors including social and financial support, as well as reliable
      and stable housing.

PMID- 30094739
TI  - Process Evaluation of a Pilot Intervention for Psychosocial Rehabilitation for
      Service Users with Schizophrenia in North West Province, South Africa.
AB  - This study investigated a non-specialist delivered programme for psychosocial
      rehabilitation for service users with schizophrenia in a low-resource South
      African setting. Forty-four service users with schizophrenia living in the
      community, receiving ongoing medication through primary care, participated in a
      structured support group. Quantitative measures (WHODAS 12 item, Brief
      Psychiatric Rating Scale and Internalized Stigma of Mental Illness Inventory)
      were assessed at baseline and 12 months. Sixteen service users were interviewed
      on their experiences. WHODAS data showed a small reduction. ISMI assessment
      showed a statistically significant reduction. Qualitative data revealed: improved
      self-esteem and increased illness knowledge, reduced risk taking, reduced social
      isolation and improved pro-social behavior, improved financial management and
      engagement in income generation activities as well as improved acceptance by the
      community. This study provides preliminary evidence on the benefits of this
      programme that warrant further study incorporating experimental methods.

PMID- 30094741
TI  - Transcriptional Study Revealed That Boron Supplementation May Alter the Immune
      Related Genes Through MAPK Signaling in Ostrich Chick Thymus.
AB  - The objective of this study is to construct a digital gene expression tag profile
      to identify genes potentially related to immune response in the ostrich. Exposure
      to boron leads to an immune response in the ostrich, although the underlying
      mechanism remains obscure. Thus, a dire need of biological resource in the form
      of transcriptomic data for ostriches arises to key out genes and to gain insights
      into the function of boron on the immune response of thymus. For this purpose,
      RNA-Seq analysis was performed using the Illumina technique to investigate
      differentially expressed genes in ostrich thymuses treated with different boric
      acid concentrations (0, 80, and 640 mg/L). Compared with the control group, we
      identified 309 upregulated and 593 downregulated genes in the 80 mg/L treated
      sample and 228 upregulated and 1816 downregulated genes in 640 mg/L treated
      sample, respectively. Trend analysis of these differentially expressed genes
      uncovers three statistically significant trends. Functional annotation analysis
      of the differentially expressed genes verifies multiple functions associated with
      immune response. When ostrich thymuses were treated with boron, expression
      changes were observed in genes predominantly associated with MAPK and calcium
      signaling pathways. The results of this study provide all-inclusive information
      on gene expression at the transcriptional level that further enhances our
      apprehension for the molecular mechanisms of boron on the ostrich immune system.
      The calcium and MAPK signaling pathways might play a pivotal role in regulating
      the immune response of boron-treated ostriches.

PMID- 30094744
TI  - A Flemish Kermis by Peeter Baltens: fashion or Peyronie's disease?

PMID- 30094743
TI  - PETC/CT with 18F-Choline localizes hyperfunctioning parathyroid adenomas equally
      well in normocalcemic hyperparathyroidism as in overt hyperparathyroidism.
AB  - PURPOSE: Identification of pathologic parathyroid glands in primary
      hyperparathyroidism, traditionally based on neck ultrasound (US) and/or 99mTc
      Sestamibi scintigraphy, can be challenging. PET/CT with 18F-Fluorocholine (18F
      FCH) might improve the detection of pathologic parathyroid glands. We aimed at
      comparing the diagnostic performance of 18F-FCH-PET/CT with that of dual-phase
      dual-isotope parathyroid scintigraphy and neck US. METHODS: Thirty-four
      consecutive patients with primary hyperparathyroidism were prospectively
      enrolled, 7 had normocalcemic hyperparathyroidism, and 27 had classic
      hypercalcemic hyperparathyroidism. All patients underwent high-resolution neck
      US, dual-phase dual-isotope 99mTc-Pertechnetate/99mTc-Sestamibi scintigraphy, and
      18F-FCH-PET/CT. RESULTS: In the whole patients' group, the detection rates of the
      abnormal parathyroid gland were 68% for neck US, 71% for 18F-FCH-PET/CT, and only
      15% for 99mTc-Sestamibi scintigraphy. The corresponding figures in normocalcemic
      and hypercalcemic hyperparathyroidism were 57 and 70% for neck US, 70 and 71% for
      18F-FCH-PET/CT, and 0 and 18% for 99mTc-Sestamibi scintigraphy, respectively. In
      the 17 patients in whom the abnormal parathyroid gland was identified, either at
      surgery or at fine needle aspiration cytology/biochemistry, the correct detection
      rate was 82% for neck US, 89% for 18F-FCH-PET/CT, and only 17% for 99mTc
      Sestamibi scintigraphy. CONCLUSIONS: 18F-FCH-PET/CT can be considered a first
      line imaging technique for the identification of pathologic parathyroid glands in
      patients with normocalcemic and hypercalcemic hyperparathyroidism, even when the
      parathyroid volume is small.

PMID- 30094740
TI  - An Overview of Conceptualizations of Eating Disorder Recovery, Recent Findings,
      and Future Directions.
AB  - PURPOSE OF REVIEW: This review delineates issues in the conceptualization and
      operationalization of eating disorder recovery, highlights recent findings about
      recovery (since 2016), and proposes future directions. RECENT FINDINGS: A
      longstanding problem in the field is that there are almost as many different
      definitions of recovery in eating disorders as there are studies on the topic.
      Yet, there has been a general shift to accepting that psychological/cognitive
      symptoms are important to recovery in addition to physical and behavioral
      indices. Further, several operationalizations of recovery have been proposed over
      the past two decades, and some efforts to validate operationalizations exist.
      However, this work has had limited impact and uptake, such that the field is
      suffering from "broken record syndrome," where calls are made for universal
      definitions time and time again. It is critical that proposed operationalizations
      be compared empirically to help arrive at a consensus definition and that
      institutional/organizational support help facilitate this. Themes in recent
      recovery research include identifying predictors, examining
      biological/neuropsychological factors, and considering severe and enduring
      anorexia nervosa. From qualitative research, those who have experienced eating
      disorders highlight recovery as a journey, as well as factors such as hope, self
      acceptance, and benefiting from support from others as integral to the process of
      recovery. The field urgently needs to implement a universal definition of
      recovery that is backed by evidence, that can parsimoniously be implemented in
      clinical practice, and that will lead to greater harmonization of scientific
      findings.

PMID- 30094742
TI  - Review of Biosimilar Trials and Data on Adalimumab in Rheumatoid Arthritis.
AB  - PURPOSE OF REVIEW: Adalimumab is one of the top-selling drugs worldwide. Its
      imminent patent expiration has seen the emergence of numerous biosimilar agents.
      In this article, we recap the evidence from bio-originator trials in rheumatoid
      arthritis (RA) to provide context for a critical review of biosimilar trial data.
      RECENT FINDINGS: Currently, three adalimumab biosimilars are approved in Europe
      and/or the USA: Amgen's ABP 501 (AMJEVITA/Solymbic), Boehringer Ingelheim's BI
      695501 (Cyltezo) and Samsung Bioepis's SB5 (Imraldi). All three agents met their
      pre-specified equivalence criteria. Subtle differences in adverse events and
      clinical responses between the reference and biosimilar products were noted. The
      introduction of adalimumab biosimilars will offer exciting opportunities in
      improving treatment access and increasing treatment options for RA and other
      licensed indications. Real-world data will further provide assurances on efficacy
      as well as safety.

PMID- 30094745
TI  - "Crucifixion" (1512) in the Benedictine Monastery of Brugora.

PMID- 30094746
TI  - Psychometric Models of Small Group Collaborations.
AB  - The social combination theory of group problem solving is used to extend existing
      psychometric models to collaborative settings. A model for pairwise group work is
      proposed, the implications of the model for assessment design are considered, and
      its estimation is addressed. The results are illustrated with an empirical
      example in which dyads work together on a twelfth-grade level mathematics
      assessment. In conclusion, attention is given to avenues of research that seem
      most fruitful for advancing current initiatives concerning the assessment of
      collaboration, teamwork, and related constructs.

PMID- 30094747
TI  - The Role of Physical Activity in Managing Fatigue in Cancer Survivors.
AB  - PURPOSE OF REVIEW: This review provides an up-to-date overview of the evidence
      relating to how physical inactivity ameliorates cancer-related fatigue. A summary
      of the postulated biological mechanisms underpinning the relationship is
      presented. RECENT FINDINGS: Systematic reviews and meta-analyses synthesising the
      results of randomised controlled trials of physical activity interventions to
      reduce fatigue broadly conclude that aerobic and combination exercise may be the
      most helpful, while resistance training alone is less efficacious. Further, light
      and moderate-intensity physical activity interventions appeared to reduce
      fatigue, whereas vigorous-intensity activity may exacerbate the condition.
      Physical activity interventions result in greater reductions in cancer-related
      fatigue when delivered post-treatment. Biological mechanisms that may explain how
      physical activity can improve different elements of cancer-related fatigue
      include inflammation; the hypothalamic-pituitary-adrenal (HPA) axis and circadian
      rhythm dysregulation; serotonin dysregulation; and alterations in ATP and muscle
      metabolism. Physical activity is well tolerated by cancer survivors and results
      in modest improvements in cancer-related fatigue. Much of the research in this
      field has been from small-scale feasibility trials. In order to help clinicians
      and allied health professionals tailor exercise prescriptions to individual
      needs, further research is required. New trials in this field should implement
      rigorous inclusion criteria, be fully powered to detect effects in sub-group
      analyses, incorporate multiple sites, and have well-defined control conditions.
      There is also a need to better understand how physical activity affects different
      subtypes of cancer-related fatigue.

PMID- 30094748
TI  - Epidemiology and management practices for childhood-onset systemic lupus
      erythematosus patients: a survey in Latin America.
AB  - To assess epidemiology and management practices of Latin America Pediatric
      Rheumatologists (LAPR) about childhood-onset systemic lupus erythematosus (cSLE).
      A cross-sectional study was performed in 288 LAPR PANLAR members based on online
      survey about cSLE practices. The response rate of web-based survey by LAPR was
      170/288(59%) and the majority worked in university hospitals (63%). The ACR
      and/or SLICC classification criteria (99%) and disease activity tools (97%) were
      almost universally used by LAPR, whereas damage index (70%) and CHAQ (58%)
      instruments were less frequently used. Laboratory exams, diagnostic imaging, and
      biopsies were generally available (> 75%), however low availability for
      densitometry (66%). Drug access was excellent for the most common prescribed
      medications (> 75%), except for belimumab (11%). Emerging mosquito-borne diseases
      were also reported: dengue (20%), chikungunya (11%), and Zika (8%). Groups were
      further divided in two, according to the median number of cSLE patients followed
      by LAPR in the last year: groups A and B (>= 25 and < 25, respectively).
      Frequencies of condom in combination with other contraceptive methods were
      significantly higher in group A than B (p = 0.01). The frequencies of reported
      pregnancy (p < 0.001) and non-adherence to therapy were significantly higher in
      group A (p = 0.023). Alcohol intake (p = 0.004) and illicit drug use (p = 0.007)
      were also reported more frequently by LAPR of group A in at least one cSLE
      patient. This first large web-based survey demonstrated an overall excellent
      access for diagnosis and therapy by LAPR, probably related to their high rate of
      practices in tertiary care of university hospitals. Adherence to therapy,
      pregnancy, and substance abuse was identified as major challenges in this
      population, particularly in larger centers.

PMID- 30094751
TI  - Non-albumin proteinuria as a parameter of tubulointerstitial inflammation in
      lupus nephritis.
AB  - Tubulointerstitial inflammation (TI) has prognostic significance in the renal
      outcomes of lupus nephritis. Here, we aimed to determine whether non-albumin
      proteinuria is associated with TI severity and with the renal response in lupus
      nephritis. We included patients with biopsy-confirmed lupus nephritis at a
      tertiary medical center in Korea from January 2011 to April 2017. Patients in
      whom the urine protein/creatinine ratio (uPCR) and the urine albumin/creatinine
      ratio (uACR) were measured simultaneously were included. Laboratory data and
      renal pathology were reviewed. Non-albumin proteinuria was calculated by
      subtracting uACR from uPCR. The renal response was assessed by the amount of
      proteinuria present at 6 months after treatment with immunosuppressants. Logistic
      regression analyses were performed to identify factors associated with TI
      severity and renal response. Out of 45 patients, 36 (80%) had no-to-mild TI,
      whereas 9 (20%) had moderate-to-severe TI. Proliferative (class III +/- V/IV +/-
      V) and nonproliferative (class II/V) glomerulonephritis (GN) were present in 38
      (84.4%) and 7 (15.6%) patients, respectively. In the logistic regression
      analyses, non-albumin proteinuria (uPCR - uACR) was associated with moderate-to
      severe TI (odds ratio [OR] 3.166, 95% confidence interval [95% CI] 1.145-8.757, p
      = 0.026) and was inversely associated with complete renal response (adjusted OR
      0.180, 95% CI 0.045-0.718, p = 0.015). In lupus nephritis, non-albumin
      proteinuria was associated with TI severity and with poor renal response after
      immunosuppressive treatment. Thus, the determination of non-albumin proteinuria
      can provide clinically valuable information on lupus nephritis.

PMID- 30094749
TI  - Prevalence, severity, and predictors of dry eye and dry mouth in Chinese patients
      with primary Sjogren syndrome.
AB  - Dry eye and dry mouth are typical clinical symptoms of primary Sjogren's syndrome
      (pSS), yet not considered in the assessment of severity and predictors in China.
      This study aimed to investigate the prevalence, severity, and potential
      predictors of dry eye/dry mouth among Chinese pSS patients. A cross-sectional
      study was conducted from the Affiliated Hospital of Nantong University. A series
      of questionnaires were applied: Ocular Surface Disease Index (OSDI), EULAR
      Sjogren's Syndrome Patient Reported Index (ESSPRI)-dry mouth items, fatigue
      severity scale (FSS), the 10 cm visual analog scale (VAS). Laboratory
      examinations were taken to obtain some biochemical indicators (i.e., C-reactive
      protein, erythrocyte sedimentation rate, anti-SSA/SSB antibody). Stepwise
      logistic/linear regression model was used to investigate the potential predictors
      of dry eye/dry mouth, respectively. Statistical analysis was performed using SPSS
      version 20.0. Two hundred twenty-four pSS patients were included in this study.
      Among them, 215 (95.98%) patients reported ESSPRI-dry mouth items score > 0, and
      the mean score was 4.92 +/- 2.43. In addition, according to the score of OSDI, 84
      (37.5%) subjects reported non-dry eye, whereas 140 (62.5%) subjects reported dry
      eye (44 mild, 31 moderate, 65 severe), and the mean of the total OSDI score was
      25.01 +/- 23.58. Then, using logistic regression and linear regression
      respectively, we found that age and fatigue were the potential predictors of dry
      eye, whereas dry mouth was predicted by age, fatigue, total pain, and ESR. The
      results of this study suggested that rheumatologists should pay attention to pSS
      patients' dry eye and dry mouth, especially those with older age, higher level of
      ESR, more severe fatigue, and pain.

PMID- 30094750
TI  - Angiotensin II type 1 receptor gene polymorphism and serum angiotensin-converting
      enzyme level in Egyptian children with systemic lupus erythematosus.
AB  - Angiotensin II, the major effective molecule of the renin-angiotensin system,
      plays a vital role in the development of systemic lupus erythematosus (SLE). To
      study angiotensin II type 1 receptor (AT1R) gene polymorphism at (A1166C) in
      Egyptian children with SLE and its correlation with serum ACE level and SLE
      manifestations. AT1R gene polymorphism (A1166C) was done in 123 children with SLE
      in comparison to 100 healthy controls using polymerase chain reaction-based
      restriction fragment length polymorphism method (PCR-RFLP) and the tetra-primer
      amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR)
      to confirm the results of the genotyping. Serum ACE level measurement was done
      using ELISA technique. The frequencies of C-containing genotypes (AC + CC) and C
      allele of AT1R (A1166C) were significantly higher in SLE patients compared to
      controls (p < 0.0001, OR = 4.9, 95% CI = 2.7-8.8; p ? 0.0001, OR = 3.6, 95% CI =
      2.2-5.9, respectively). Lupus nephritis (LN) patients had significantly higher
      frequency of (AC + CC) genotypes and C-allele compared with controls (p ? 0.0001,
      OR = 5.1, 95% CI = 2.7-9.7; p ? 0.0001, OR = 3.5, 95% CI = 2.1-6.02,
      respectively). Mean serum ACE levels were significantly higher in SLE patients
      compared to controls (p ? 0.0001). There were no associations between AT1R gene
      polymorphism and serum ACE level and the clinical manifestations of SLE. The AT1R
      gene polymorphism can be considered a risk factor for the development of SLE in
      Egyptian children.

PMID- 30094752
TI  - The impact of hospital volume on clinical and economic outcomes in ventral hernia
      repair: an analysis with national policy implications.
AB  - PURPOSE: The objectives of this study are to evaluate the associations between
      ventral hernia repair procedure volume and patient outcomes, including both
      clinical and economic outcomes. METHOD: The 2014 National Inpatient Sample was
      queried for patients who underwent elective, open ventral (incisional) hernia
      repair with or without mesh. Outcomes included occurrence of major or wound-based
      in-hospital complications, extended length of stay (> 4 days), and increased
      costs (> $12,816). High-volume hospitals were defined as the 90th percentile of
      case volume or higher (> 60 cases/year). Multivariate regression was performed to
      access the outcomes associated with high-volume hospitals. RESULTS: 54,075
      patients at 2049 hospitals were retrieved. 41.4 percent of patients were treated
      at high-volume hospitals. Patients treated at high-volume hospitals were less
      likely to experience a major complication (OR 0.88; 95% CI 0.82-0.96; p = 0.002)
      or wound-based complication (OR 0.84; 95% CI 0.76-0.92; p < 0.001). However, in
      terms of resource utilization, patients treated at high-volume hospitals were
      more likely to experience an extended length of stay (OR 1.14; 95% CI 1.09-1.12;
      p < 0.001) and an increase in costs (OR 1.23; 95% CI 1.17-1.29; p < 0.001).
      CONCLUSION: Hospitals that perform a larger number of ventral hernia repairs,
      despite caring for a more complex patient population, may be associated with
      better patient outcomes than lower volume hospitals. However, these same high
      volume centers demonstrate an extended length of stay and increased costs.
      Further research is needed to understand the reason for this gap in proper
      resource utilization in high-volume ventral hernia repair centers.

PMID- 30094754
TI  - Comparison of Swab Sampling Methods for Norovirus Recovery on Surfaces.
AB  - Human noroviruses (HuNoVs) can be easily transferred by the contacts of humans or
      fomites. Swab sampling methods are widely used for recovering HuNoVs from small
      surfaces of various fomites or hard-to-reach locations and swab sampling
      conditions are important for the accurate detection of HuNoVs, which have a low
      infectious dose and relatively long persistence under a range of environmental
      conditions. Therefore, to determine the suitable swab sampling method for
      recovering HuNoVs from various surfaces, we evaluated combinations of four swab
      materials (cotton, microdenier polyester [a type of microfiber], polyurethane
      foam, and rayon) and three elution buffer solutions (phosphate-buffered saline
      [PBS], PBS with 0.2% Tween-80, and 3% beef extract-50 mM glycine [pH 9.5]).
      First, we inoculated HuNoVs or murine noroviruses (MuNoVs), the surrogate of
      HuNoVs, onto test coupons (10 * 10 cm) consisting of three common surface
      materials (high-density polyethylene, stainless steel, and wood). Coupons were
      swabbed using a combination of each swab material and elution buffer, and the
      viral recovery was measured by real-time reverse transcription quantitative
      polymerase chain reaction (RT-qPCR) or plaque assay. By RT-qPCR, we confirmed
      that the cotton swab-PBS and microdenier polyester-PBS combinations had recovery
      efficiencies greater than 80% for viruses on plastic and stainless steel
      surfaces. The cotton swab-PBS combination had the highest recovery efficiency on
      all surface materials via the plaque assay. Therefore, a cotton or a microdenier
      polyester swab with PBS could be a useful method for sampling HuNoVs on various
      surfaces.

PMID- 30094755
TI  - Determination of geometric accuracy of radiotherapy fields by port film and DRR
      using Matlab graphical user interface.
AB  - The purpose of this study is to determine and verify the exact location of
      radiation therapy fields by using port-film and digital reconstruction radiograph
      (DRR) as a low-cost tool. Initially, an appropriate algorithm was written for the
      application of port film in the megavoltage beam irradiation. Detectable contrast
      was created for the image and then by using appropriate markers and developed
      written program by MATLAB as DRrPortRegistartion. Semi-automatic and automatic
      registration between port-film and DRR images were performed for pelvic and chest
      phantoms. Then, results were compared with electronic portal imaging device
      (EPID) images in similar conditions. By using this software, DRR and port film as
      treatment verification tools, the precision of treatment verification and the
      accuracy of radiation therapy fields were achieved in the extent of the
      millimeter. Validation results with EPID demonstrated that the mean absolute
      average error in angle is equal to 0.59 degrees, 1.70 mm in the X-direction, and
      2.42 mm in the Y-direction. The results of this study illustrated that using this
      software and suitable low-cost hardware in the machines without EPID can increase
      the precision of treatment verification to the millimeter and it can be
      introduced as a suitable alternative for EPID in centers for increasing treatment
      accuracy. Graphical abstract ?.

PMID- 30094753
TI  - A Narrative Review of Four Different New Techniques in Primary Anterior Cruciate
      Ligament Repair: "Back to the Future" or Another Trend?
AB  - Recently, four different operative techniques, referring to the primary anterior
      cruciate ligament (ACL) repair, were described. These are the dynamic
      intraligamentary stabilization (DIS) with LigamysTM, the Bridge-enhanced repair
      (BEAR), the use of internal brace, and the refixation with suture anchors. The
      purpose of this study was to assess the already-published, clinical, and pre
      clinical results of those techniques. A literature review was conducted and
      implemented by three independent researchers. Inclusion criteria were clinical or
      cadaveric or animal studies about patients suffering from ACL rupture, who were
      treated with one of those four different arthroscopic techniques of primary ACL
      repair. There were 10 clinical trials dealing with the different techniques of
      primary ACL repair and 12 cadaveric or animal studies. The majority of the
      published clinical trials investigated the dynamic intraligamentary stabilization
      (DIS), while only four studies referred to the three other surgical techniques.
      Most of the clinical trials suggested that primary ACL repair should be done
      during the first 14-21 days after a proximal ACL rupture and not later. Further
      clinical evidence is needed for the techniques of bridge-enhanced ACL repair,
      internal brace, and suture anchors ACL refixation in order to support the animal
      and cadaveric biomechanical studies. Till now, the existing clinical trials were
      not enough to establish the use of those techniques in the ACL-ruptured patients.
      On the contrary, the Dynamic intraligamentary stabilization with LigamysTM device
      demonstrated very promising results in different types of clinical studies.

PMID- 30094757
TI  - Deletion of the Transcription Factor PGC-1alpha in Mice Negatively Regulates Bone
      Mass.
AB  - Peroxisome proliferator-activated receptor-gamma coactivator (PGC1alpha) is a
      transcription coactivator that interacts with a broad range of transcription
      factors involved in several biological responses. Here, we show that PGC1alpha
      plays a role in skeletal homeostasis since aged PGC1alpha-deficient mice
      (PGC1alpha-/-) display impaired bone structure. Micro-CT of the tibial mid-shaft
      showed a marked decrease of cortical thickness in PGC1alpha-/- (- 11.9%, p <
      0.05) mice compared to wild-type littermate. Trabecular bone was also impaired in
      knock out mice which displayed lower trabecular thickness (Tb.Th) (- 5.9% vs
      PGC1alpha+/+, p < 0.05), whereas trabecular number (Tb.N) was higher than wild
      type mice (+ 72% vs PGC1alpha+/+, p < 0.05), thus resulting in increased (+ 31.7%
      vs PGC1alpha+/+, p < 0.05) degree of anisotropy (DA), despite unchanged bone
      volume fraction (BV/TV). Notably, these impairments of cortical and trabecular
      bone led to a dramatic ~ 48.4% decrease in bending strength (p < 0.01). These
      changes in PGC1alpha-/- mice were paralleled by a significant increase in
      osteoclast number at the cortical bone surface and in serum level of the bone
      resorption marker, namely, C-terminal cross-linked telopeptides of type I
      collagen (CTX-I). We also found that in cortical bone, there was lower expression
      of mRNA codifying for the key bone-building protein Osteocalcin (Ocn).
      Interestingly, Collagen I mRNA expression was reduced in mesenchymal stem cells
      from bone marrow of PGC1alpha-/-, thus indicating that differentiation of
      osteoblast lineage is downregulated. Overall, results presented herein suggest
      that PGC1alpha may play a key role in bone metabolism.

PMID- 30094756
TI  - Measuring acute stress response through physiological signals: towards a
      quantitative assessment of stress.
AB  - Social and medical problems associated with stress are increasing globally and
      seriously affect mental health and well-being. However, an effective stress-level
      monitoring method is still not available. This paper presents a quantitative
      method for monitoring acute stress levels in healthy young people using
      biomarkers from physiological signals that can be unobtrusively monitored. Two
      states were induced to 40 volunteers, a basal state generated with a relaxation
      task and an acute stress state generated by applying a standard stress test that
      includes five different tasks. Standard psychological questionnaires and
      biochemical markers were utilized as ground truth of stress levels. A
      multivariable approach to comprehensively measure the physiological stress
      response is proposed using stress biomarkers derived from skin temperature, heart
      rate, and pulse wave signals. Acute physiological stress levels (total-range 0
      100 au) were continuously estimated every 1 min showing medians of 29.06 au in
      the relaxation tasks, while rising from 34.58 to 47.55 au in the stress tasks.
      Moreover, using the proposed method, five statistically different stress levels
      induced by the performed tasks were also measured. Results obtained show that, in
      these experimental conditions, stress can be monitored from unobtrusive
      biomarkers. Thus, a more general stress monitoring method could be derived based
      on this approach. Graphical abstract Stress measurements of different healthy
      young people throughout a Stress Session that includes a pre-relax stage (BLs),
      memory test (ST and MT), stress anticipation time (SA), video display (VD) and
      arithmetic task.

PMID- 30094758
TI  - SB203580 attenuates acute lung injury and inflammation in rats with acute
      pancreatitis in pregnancy.
AB  - Acute pancreatitis in pregnancy (APIP) can lead to multiple maternal and fetal
      organ injury and mitogen-activated protein kinase (MAPK) signaling pathway may be
      involved in it; however, whether APIP can result in acute lung injury and P38MAPK
      signaling pathway is involved in the pathogenesis has not been elucidated. The
      present study was undertaken to investigate the participation of P38MAPK
      signaling pathway and the protective effect of SB203580, an inhibitor of P38MAPK
      on acute lung injury induced by APIP. Twenty-four late-gestation SD rats were
      randomly assigned to four groups: Sham operation (SO) group, SB302580 (SB) group,
      APIP group, and SB + APIP group. All the rats were killed 6 h after modeling. The
      severity of pancreatitis was evaluated by serum amylase (AMY) and lipase (LIPA)
      and histopathological changes. Histological assessment of the lung and
      inflammatory cell infiltration was performed by H&E and immunofluorescence assay.
      The lung wet/dry (W/D) weight ratio was determined, and the levels of tumor
      necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 were detected
      by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to
      detect the protein expression of phosphorylated and total P38, tumor necrosis
      factor (TNF)-alpha, and intercellular adhesion molecules 1 (ICAM-1) in lung
      tissues. Obvious pathological changes existed in pancreas and lung after the
      induction of APIP, and their pathological scores were significantly higher than
      that of control group. The results showed that the phosphorylation of P38MAPK was
      elevated in the lung of APIP rats. Compared with APIP group, the intervention of
      SB203580 alleviated the pathological injury of the pancreas and lungs, decreased
      serum AMY and LIPA, attenuated the secretion of TNF-alpha, IL-1beta, and IL-6 in
      lung, reduced the inflammatory cells' infiltration and lung W/D ratio and
      inhibited the activation of P38MAPK signaling pathway. These results suggest that
      APIP can lead to acute lung injury and inflammation and SB203580 can inhibit the
      lung injury by inhibiting the P38MAPK signaling pathway and blocking the
      inflammatory responses.

PMID- 30094759
TI  - In vitro fertilization with granulosa cell tumor: a report of two cases.

PMID- 30094761
TI  - The impact of specialization of hospitals on patient access to care; a queuing
      analysis with an application to a neurological hospital.
AB  - We study the impact of specialization on the operational efficiency of a multi
      hospital system. The mixed outcomes of recently increasing hospital mergers and
      system re-configuration initiatives have raised the importance of studying such
      organizational changes from all the relevant perspectives. We consider two
      configuration scenarios for a multi-hospital system. The first scenario assumes
      that all the hospitals in the system are general, which implies they can provide
      care to all types of patients. In the alternative configuration, we specialize
      each hospital in certain level of care, which means they serve only specific
      types of patients. By considering an extensive number of possible settings for a
      multi-hospital system, we characterize the situations in which one scenario
      outperforms the other in terms of extending access of patients to care. Our
      results show that whenever the percent of patients with shorter length of stay in
      the system increases, specialization of healthcare services can maximize the
      accessibility of care. Also, if the patient load is balanced between all
      hospitals in the system, it seems more likely that all hospitals benefit from
      specialization. We conclude that the strategic decision of designing a multi
      hospital system requires careful consideration of patient mix among arrivals,
      relative length of stay of patients, and distribution of patient load between
      hospitals.

PMID- 30094763
TI  - Is There a Role for Internal Medicine Residency Preparation Courses in the Fourth
      Year Curriculum? A Single-Center Experience.

PMID- 30094760
TI  - Respirometric reserve capacity of cumulus cell mitochondria correlates with
      oocyte maturity.
AB  - PURPOSE: Oocyte competence is critical in success of assisted reproduction.
      Metabolic signaling between oocyte and cumulus cells within the cumulus-oocyte
      complex procure oocyte development. This study evaluated the relationship between
      respirometric activity of cumulus cells and maturity of corresponding oocytes.
      METHODS: In prospective cohort study, 20 women of age 28-42 undergoing IVF
      procedure were involved. To evaluate oocyte maturity, the cumulus cells from
      individual oocytes were assessed flow cytometrically by double labeling of cells
      with mitochondria specific dyes. The respirometric stress analysis using ATPase
      inhibitor oligomycin was applied to assess mitochondria metabolic abnormalities.
      RESULTS: The cumulus cells from each of 327 oocytes were analyzed. The
      respirometric index of cumulus cells (O'R) strongly correlates with maternal
      ovarian reserve, showing to be higher in patients with higher AMH (p < 0.0017).
      Cumulus cells from immature oocytes had severe mitochondria deficiency, i.e., low
      O'R, than those from mature oocytes (p < 0.02). No significant difference in
      respirometric capacity was found between cumulus cells associated with good vs
      poor-quality embryos. CONCLUSIONS: The oocyte maturity is potentially related to
      the mitochondria activity of cumulus cells.

PMID- 30094762
TI  - Detectability, visualization, and DNA analysis of bloodstains after repainting
      the walls.
AB  - A recurrent observation in forensic casework is that culprits and/or their
      abettors attempt to remove or mask bloodstain patterns, e.g., by painting the
      walls. The present study was designed to elucidate whether luminol treatment of
      bloodstains on (a) plastered and (b) wallpapered walls may help with the
      visualization of respective patterns after being repainted beyond macroscopic
      recognition. Furthermore, wallpaper punches of luminol-positive spots were
      analyzed for DNA. The experiments showed that the prospects for visualization
      after a four- to sixfold paint application declined considerably as the drying
      time of the paint increased. A compelling explanation for this observation is
      that paint becomes increasingly resistant to water during the drying process
      after paint application. In these cases, moistening the surface in question with
      distilled water for 15 min has been proven to be a promising pretreatment before
      luminol application. DNA analysis revealed full STR profiles in 74% of luminol
      positive wallpaper punches, whereas rubs of the aforementioned positively tested
      regions (luminol and human blood pretests) demonstrated negative results.

PMID- 30094765
TI  - Indirect Doppler ultrasound abnormalities of significant portal vein stenosis
      after liver transplantation.
AB  - PURPOSE: To determine indirect Doppler ultrasound (DUS) abnormalities associated
      with significant portal vein (PV) stenosis (PVS) in recipients of liver
      transplantation (LT). METHODS: This retrospective study was approved by our
      institutional review board. Between February 2006 and May 2017, 41 LT recipients
      were diagnosed with significant PVS, defined as having more than 50% narrowing of
      PV diameter for any reason, including thrombosis or flow disturbance associated
      with prominent collateral vessels on portal venography. We reviewed the DUS
      findings of hepatic arteries (HAs) as well as PVs of them, before and after
      treatment of PVS, and in comparison, with a one-to-one case-matched control.
      Inter-group comparison of frequency in DUS abnormalities was performed using Chi
      square (chi2) with Fisher's exact test and McNemar's test. Diagnostic values of
      each abnormal DUS finding and combinations were also evaluated. RESULTS: DUS of
      significant PVS showed "no demonstrable color flow," either at recipient PVs or
      anastomoses (26.7%), and showed turbulence (66.7%) and hepatofugal portal flow
      (HFPF; 20.0%) at the graft PVs. HFPF was more frequently observed in those with
      "no demonstrable color flow" at recipient PVs or anastomoses (p = 0.006). DUS of
      graft HAs revealed tardus-parvus waveforms (20.9%) and prolonged systolic
      acceleration times (16.3%), more commonly in the "no demonstrable color flow"
      group (p = 0.012). These indirect DUS abnormalities disappeared and resolved on
      follow-up DUS after treatment. In the control group, such Doppler abnormalities
      were less frequently shown than in the PVS group (p <= 0.01, respectively). When
      one of the portal-blood flow velocity (PFV)-related index abnormalities (such as
      increased time average velocity [TAV] at anastomosis and TAV ratio between
      recipient PV and anastomosis) or "no demonstrable color flow" were shown in DUS
      as well as one of the indirect DUS abnormalities, sensitivity, and specificity
      was 71.11 and 97.78%, respectively. CONCLUSION: In addition to PFV-related
      abnormalities, DUS occasionally shows "no demonstrable color flow" either at
      recipient PVs or anastomoses, and indirect Doppler abnormalities such as
      turbulence, HFPF at graft PVs, and abnormal waveforms at graft HAs in LT
      recipients with significant PVS. The combination of PFV-related abnormalities and
      indirect DUS abnormalities would be helpful for diagnosis of PVS.

PMID- 30094764
TI  - Land use/land cover change and its impacts on protected areas in Mengla County,
      Xishuangbanna, Southwest China.
AB  - Land use/land cover change (LUCC) in tropical areas threatens biodiversity and
      protected area integrity and then affects global ecosystem functions and
      services. In this study, the spatiotemporal patterns and processes of LUCC in
      Mengla County, Xishuangbanna, which is located on the northern edge of tropical
      Asia, were examined using a modified post-classification change detection
      technique based on random forest classifiers and Landsat images acquired at a 5
      year time interval (e.g., 1994, 1999, 2004, 2009, and 2014) from 1994 to 2014,
      with a special focus on protected areas and their surroundings. The overall
      accuracies of land use/land cover classification reached 90.13-97.90%, with kappa
      coefficients of 0.84-0.96. Massive but decelerating conversion from forests to
      artificial plantations has occurred in recent decades. From 1994 to 2014, the
      area of plantations increased by 1833.85 km2, whereas that of forests decreased
      by 1942.67 km2. The expanded areas of artificial plantations decreased from
      158.41 km2 per year in 1994-1999 to 59.70 km2 per year in 2009-2014. More
      considerable transformation from forests to artificial plantations occurred in
      lowland areas with elevations below 1000 m and at the edges of National Nature
      Reserves, which observed a forest loss rate of greater than 40% between 1994 and
      2014. This poses serious challenges for sustaining both protected areas and
      surrounding human communities and to solve the increasingly escalating human
      elephant conflicts. The complex food, biodiversity, and land use nexus in this
      region remain to be untangled in future study.

PMID- 30094767
TI  - Delayed hemopericardium due to non-penetrating chest trauma: a report of new case
      and literature review.
AB  - To our knowledge, only 15 cases of delayed traumatic hemopericardium resulting
      from non-penetrating chest trauma have been reported. We present the case of a 63
      year-old man with delayed hemopericardium, 2 months after striking the anterior
      chest on a mailbox when he fell down three steps during a postal delivery. Our
      case and review of the previously reported cases suggest that some cases might
      show quite slow progression of blood accumulation. Therefore, careful observation
      of patients who have experienced blunt trauma of the anterior chest is necessary.

PMID- 30094766
TI  - Prenatal findings of serpentine-like syndrome with congenital intrathoracic
      stomach: differential diagnosis from congenital diaphragmatic hernia.
AB  - Congenital rachischisis and brachioesophagus with secondary intrathoracic
      stomach, which is described as "serpentine-like syndrome", is a very rare
      condition. We report the prenatal findings of serpentine-like syndrome in a fetus
      at 18 weeks of gestation. The stomach was entirely elevated into the thoracic
      area, but the liver retained its normal position. Our initial diagnosis was
      isolated left congenital diaphragmatic hernia (CDH). At 20 weeks of gestation,
      the pregnancy was terminated, and a male newborn weighing 338 g was vaginally
      delivered. The autopsy findings revealed an extremely short esophagus, and the
      stomach was located in the posterior mediastinum as a result of congenital
      esophagus hiatal hernia. A severe case of rachischisis was identified from the
      cervical to thoracic vertebrae. The prognosis of congenital intrathoracic stomach
      associated with serpentine-like syndrome is extremely poor compared to the
      prognosis of isolated CDH. It is difficult to make a definite diagnosis by
      ultrasound alone; however, atypical findings, such as the presence of the entire
      intrathoracic stomach despite the normally located liver, may warrant further
      exploration. Obstetricians and neonatal clinicians presented with similar cases
      should be alerted to the significance of these prenatal findings and the
      differences in outcomes to ensure appropriate counseling of parents.

PMID- 30094769
TI  - Optimal Mating Strategies for Preferentially Outcrossing Simultaneous
      Hermaphrodites in the Presence of Predators.
AB  - The optimal timing for initiating reproduction (i.e., the age at first
      reproduction) is a critical life history trait describing aspects of an
      individual's resource-allocation strategy. Recent theoretical and empirical work
      has demonstrated that this trait is also tied to mating system expression when
      individuals have the opportunity to reproduce via both self-fertilization and
      cross-fertilization. A strategy of "delayed selfing" has emerged as a "best of
      both worlds" arrangement where, in the absence of a mate, an individual will
      delay reproduction (selfing) to "wait" for a mate. Herein, we extend previously
      developed predictive optimization models for the timing of reproduction to a
      situation where organisms can allocate their resources to size-dependent and size
      independent defensive strategies to counter the threat of predation. By
      incorporating inducible defenses into a predictive framework for analyzing life
      history expression and evolution, we can more accurately evaluate the role that
      allocation strategy plays in altering the optimal waiting time. We compare our
      model to previous models and empirical results highlighting that incorporation of
      inducible defenses into the model broadens the parameter space in which a waiting
      time is expected and often leads to a predicted waiting time that is longer than
      in the situation without inducible defenses. In particular, a waiting time is
      predicted to exist regardless of the strength of inbreeding depression in the
      population.

PMID- 30094768
TI  - The discourse on faith and medicine: a tale of two literatures.
AB  - Research and writing at the intersection of faith and medicine by now include
      thousands of published studies, review articles, books, chapters, and essays. Yet
      this emerging field has been described, from within, as disheveled on account of
      imprecision and lack of careful attention to conceptual and theoretical concerns.
      An important source of confusion is the fact that scholarship in this field
      constitutes two distinct literatures, or rather meta-literatures, which can be
      termed (a) faith as a problematic for medicine and (b) medicine as a problematic
      for faith. These categories represent distinct theoretical lenses for viewing the
      intersection of faith and medicine. Observations about these two approaches are
      offered, along with insights about why the discourse on faith and medicine should
      become better integrated into discussions of religion and science.

PMID- 30094770
TI  - A Stochastic Model for Reproductive Isolation Under Asymmetrical Mating
      Preferences.
AB  - More and more evidence shows that mating preference is a mechanism that may lead
      to a reproductive isolation event. In this paper, a haploid population living on
      two patches linked by migration is considered. Individuals are ecologically and
      demographically neutral on the space and differ only on a trait, a or A,
      affecting both mating success and migration rate. The special feature of this
      paper is to assume that the strengths of the mating preference and the migration
      depend on the trait carried. Indeed, patterns of mating preferences are generally
      asymmetrical between the subspecies of a population. I prove that mating
      preference interacting with frequency-dependent migration behavior can lead to a
      reproductive isolation. Then, I describe the time before reproductive isolation
      occurs. To reach this result, I use an original method to study the limiting
      dynamical system, analyzing first the system without migration and adding
      migration with a perturbation method. Finally, I study how the time before
      reproductive isolation is influenced by the parameters of migration and of mating
      preferences, highlighting that large migration rates tend to favor types with
      weak mating preferences.

PMID- 30094771
TI  - A Model for the Acrosome Reaction in Mammalian Sperm.
AB  - The acrosome reaction is a complex, calcium-dependent reaction that results in an
      exocytotic event required for successful fertilization of the egg. It has long
      been thought that the acrosome reaction occurs upon sperm binding to the zona
      pellucida, a viscoelastic layer surrounding the oocyte. Recent studies have
      suggested that the reaction may even occur before the sperm encounters the zona,
      perhaps mediated by progesterone or some other agonist. It has been particularly
      difficult to understand differences between progesterone-induced and zona-induced
      reactions experimentally and whether one substance is the more biologically
      relevant trigger. Until this present work, there has been little effort to
      mathematically model the acrosome reaction in sperm as a whole. Instead,
      attention has been paid to modeling portions of the pathways involved in other
      cell types. Here we present a base model for the acrosome reaction which
      characterizes the known biochemical reactions and behaviors of the system. Our
      model allows us to analyze several pathways that may act as a stabilizing
      mechanism for avoiding sustained oscillatory calcium responses often observed in
      other cell types. Such an oscillatory regime might otherwise prevent acrosomal
      exocytosis and therefore inhibit fertilization. Results indicate that the
      acrosome reaction may rely upon multiple redundant mechanisms to avoid entering
      an oscillatory state and instead maintain a high resting level of calcium, known
      to be required for successful acrosomal exocytosis and, ultimately, fertilization
      of the oocyte.

PMID- 30094772
TI  - Identifying Species Network Features from Gene Tree Quartets Under the Coalescent
      Model.
AB  - We show that many topological features of level-1 species networks are
      identifiable from the distribution of the gene tree quartets under the network
      multi-species coalescent model. In particular, every cycle of size at least 4 and
      every hybrid node in a cycle of size at least 5 are identifiable. This is a step
      toward justifying the inference of such networks which was recently implemented
      by Solis-Lemus and Ane. We show additionally how to compute quartet concordance
      factors for a network in terms of simpler networks, and explore some
      circumstances in which cycles of size 3 and hybrid nodes in 4-cycles can be
      detected.

PMID- 30094773
TI  - Monitoring Dose Response of Cyanide Antidote Dimethyl Trisulfide in Rabbits Using
      Diffuse Optical Spectroscopy.
AB  - INTRODUCTION: Cyanide (CN) poisoning is a serious chemical threat from accidental
      or intentional exposures. Current CN exposure treatments, including direct
      binding agents, methemoglobin donors, and sulfur donors, have several
      limitations. Dimethyl trisulfide (DMTS) is capable of reacting with CN to form
      the less toxic thiocyanate with high efficiency, even without the
      sulfurtransferase rhodanese. We investigated a soluble DMTS formulation with the
      potential to provide a continuous supply of substrate for CN detoxification which
      could be delivered via intramuscular (IM) injection in a mass casualty situation.
      We also used non-invasive technology, diffuse optical spectroscopy (DOS), to
      monitor physiologic changes associated with CN exposure and reversal. METHODS:
      Thirty-six New Zealand white rabbits were infused with a lethal dose of sodium
      cyanide solution (20 mg/60 ml normal saline). Animals were divided into three
      groups and treated with saline, low dose (20 mg), or high dose (150 mg) of DMTS
      intramuscularly. DOS continuously assessed changes in tissue hemoglobin
      concentrations and cytochrome c oxidase redox state status throughout the
      experiment. RESULTS: IM injection of DMTS increased the survival in lethal CN
      poisoning. DOS demonstrated that high-dose DMTS (150 mg) reversed the effects of
      CN exposure on cytochrome c oxidase, while low dose (20 mg) did not fully reverse
      effects, even in surviving animals. CONCLUSIONS: This study demonstrated
      potential efficacy for the novel approach of supplying substrate for non
      rhodanese mediated sulfur transferase pathways for CN detoxification via
      intramuscular injection in a moderate size animal model and showed that DOS was
      useful for optimizing the DMTS treatment.

PMID- 30094774
TI  - The Toxicology Investigators Consortium Case Registry-the 2017 Annual Report.
AB  - The Toxicology Investigators Consortium (ToxIC) Case Registry was established by
      the American College of Medical Toxicology in 2010. The Registry collects data
      from participating sites with the agreement that all bedside medical toxicology
      consultations will be entered. The objective of this eighth annual report is to
      summarize the Registry's 2017 data and activity with its additional 7577 cases.
      Cases were identified for inclusion in this report by a query of the ToxIC
      database for any case entered from 1 January to 31 December 2017. Detailed data
      was collected from these cases and aggregated to provide information which
      includes demographics (e.g., age, gender, race, ethnicity), reason for medical
      toxicology evaluation (e.g., intentional pharmaceutical exposure, envenomation,
      withdrawal from a substance), agent and agent class, clinical signs and symptoms
      (e.g., vital sign abnormalities, organ system dysfunction), treatments and
      antidotes administered, fatality, and life support withdrawal data. Females were
      involved in 50.4% of cases. Transgender demographic information collection was
      initiated in 2017 to better represent the population and there were 36 cases
      involving transgender patients. Adults aged 19-65 were the most commonly reported
      age group. Non-opioid analgesics were the most commonly reported agent class,
      with acetaminophen again the most common agent reported. There were 93 fatalities
      reported in 2017. Treatment interventions were frequently reported with 30.6%
      receiving specific antidotal therapy. Major trends in demographics and exposure
      characteristics remained similar to past years' reports. While treatment
      interventions were commonly required, fatalities were rare.

PMID- 30094776
TI  - Embryonal Rhabdomyosarcoma (Botryoid Subtype) Affecting the Buccal Mucosa.
AB  - Rhabdomyosarcoma (RMS) is a rare oral malignant soft tissue tumor whose
      pathological features may influence the clinical behavior, treatment and
      prognosis of the lesion. We report a case of a 13-year-old female patient,
      presenting an asymptomatic polypoid swelling in the left buccal mucosa that was
      approximately 2.5 cm in diameter and 3 months evolution. The presumptive
      diagnosis was fibrous hyperplasia and an excisional biopsy was carried out.
      Pathologic analysis revealed proliferation of predominantly ovoid cells, with
      eosinophilic cytoplasm and pleomorphic nuclei, arranged in subepithelial cambium
      layer. The mucosal surface presented a papillary-verrucous appearance.
      Immunohistochemical analysis revealed intense positivity for desmin, myogenin and
      Ki-67. The diagnosis was of embryonal RMS (botryoid variant). The patient was
      subjected to complementary chemotherapy and radiotherapy, with no evidence of
      recurrence or metastatic disease after 12 months follow-up. A discussion on the
      clinical, histopathological, immunohistochemical and therapeutic aspects of
      botryoid RMS will be provided.

PMID- 30094775
TI  - Environmental Drivers of Ranavirus in Free-Living Amphibians in Constructed
      Ponds.
AB  - Amphibian ranaviruses occur globally, but we are only beginning to understand
      mechanisms for emergence. Ranaviruses are aquatic pathogens which can cause > 90%
      mortality in larvae of many aquatic-breeding amphibians, making them important
      focal host taxa. Host susceptibilities and virulence of ranaviruses have been
      studied extensively in controlled laboratory settings, but research is needed to
      identify drivers of infection in natural environments. Constructed ponds,
      essential components of wetland restoration, have been associated with higher
      ranavirus prevalence than natural ponds, posing a conundrum for conservation
      efforts, and emphasizing the need to understand potential drivers. In this study,
      we analyzed 4 years of Frog virus 3 prevalence and associated environmental
      parameters in populations of wood frogs (Lithobates sylvaticus) and green frogs
      (Lithobates clamitans) in a constructed pond system. High prevalence was best
      predicted by low temperature, high host density, low zooplankton concentrations,
      and Gosner stages approaching metamorphosis. This study identified important
      variables to measure in assessments of ranaviral infection risk in newly
      constructed ponds, including effects of zooplankton, which have not been
      previously quantified in natural settings. Examining factors mediating diseases
      in natural environments, particularly in managed conservation settings, is
      important to both validate laboratory findings in situ, and to inform future
      conservation planning, particularly in the context of adaptive management.

PMID- 30094777
TI  - Development and internal validation of an aneurysm rupture probability model
      based on patient characteristics and aneurysm location, morphology, and
      hemodynamics.
AB  - PURPOSE: Unruptured cerebral aneurysms pose a dilemma for physicians who need to
      weigh the risk of a devastating subarachnoid hemorrhage against the risk of
      surgery or endovascular treatment and their complications when deciding on a
      treatment strategy. A prediction model could potentially support such treatment
      decisions. The aim of this study was to develop and internally validate a model
      for aneurysm rupture based on hemodynamic and geometric parameters, aneurysm
      location, and patient gender and age. METHODS: Cross-sectional data from 1061
      patients were used for image-based computational fluid dynamics and shape
      characterization of 1631 aneurysms for training an aneurysm rupture probability
      model using logistic group Lasso regression. The model's discrimination and
      calibration were internally validated based on the area under the curve (AUC) of
      the receiver operating characteristic and calibration plots. RESULTS: The final
      model retained 11 hemodynamic and 12 morphological variables, aneurysm location,
      as well as patient age and gender. An adverse hemodynamic environment
      characterized by a higher maximum oscillatory shear index, higher kinetic energy
      and smaller low shear area as well as a more complex aneurysm shape, male gender
      and younger age were associated with an increased rupture risk. The corresponding
      AUC of the model was 0.86 (95% CI [0.85, 0.86], after correction for optimism
      0.84). CONCLUSION: The model combining variables from various domains was able to
      discriminate between ruptured and unruptured aneurysms with an AUC of 86%.
      Internal validation indicated potential for the application of this model in
      clinical practice after evaluation with longitudinal data.

PMID- 30094778
TI  - Transfer learning with deep convolutional neural network for liver steatosis
      assessment in ultrasound images.
AB  - PURPOSE: The nonalcoholic fatty liver disease is the most common liver
      abnormality. Up to date, liver biopsy is the reference standard for direct liver
      steatosis quantification in hepatic tissue samples. In this paper we propose a
      neural network-based approach for nonalcoholic fatty liver disease assessment in
      ultrasound. METHODS: We used the Inception-ResNet-v2 deep convolutional neural
      network pre-trained on the ImageNet dataset to extract high-level features in
      liver B-mode ultrasound image sequences. The steatosis level of each liver was
      graded by wedge biopsy. The proposed approach was compared with the hepatorenal
      index technique and the gray-level co-occurrence matrix algorithm. After the
      feature extraction, we applied the support vector machine algorithm to classify
      images containing fatty liver. Based on liver biopsy, the fatty liver was defined
      to have more than 5% of hepatocytes with steatosis. Next, we used the features
      and the Lasso regression method to assess the steatosis level. RESULTS: The area
      under the receiver operating characteristics curve obtained using the proposed
      approach was equal to 0.977, being higher than the one obtained with the
      hepatorenal index method, 0.959, and much higher than in the case of the gray
      level co-occurrence matrix algorithm, 0.893. For regression the Spearman
      correlation coefficients between the steatosis level and the proposed approach,
      the hepatorenal index and the gray-level co-occurrence matrix algorithm were
      equal to 0.78, 0.80 and 0.39, respectively. CONCLUSIONS: The proposed approach
      may help the sonographers automatically diagnose the amount of fat in the liver.
      The presented approach is efficient and in comparison with other methods does not
      require the sonographers to select the region of interest.

PMID- 30094779
TI  - Preoperative liver registration for augmented monocular laparoscopy using
      backward-forward biomechanical simulation.
AB  - PURPOSE: Augmented reality for monocular laparoscopy from a preoperative volume
      such as CT is achieved in two steps. The first step is to segment the organ in
      the preoperative volume and reconstruct its 3D model. The second step is to
      register the preoperative 3D model to an initial intraoperative laparoscopy
      image. To date, there does not exist an automatic initial registration method to
      solve the second step for the liver in the de facto operating room conditions of
      monocular laparoscopy. Existing methods attempt to solve for both deformation and
      pose simultaneously, leading to nonconvex problems with no optimal solution
      algorithms. METHODS: We propose in contrast to break the problem down into two
      parts, solving for (i) deformation and (ii) pose. Part (i) simulates
      biomechanical deformations from the preoperative to the intraoperative state to
      predict the liver's unknown intraoperative shape by modeling gravity, the
      abdominopelvic cavity's pressure and boundary conditions. Part (ii) rigidly
      registers the simulated shape to the laparoscopy image using contour cues.
      RESULTS: Our formulation leads to a well-posed problem, contrary to existing
      methods. This is because it exploits strong environment priors to complement the
      weak laparoscopic visual cues. CONCLUSION: Quantitative results with in silico
      and phantom experiments and qualitative results with laparosurgery images for two
      patients show that our method outperforms the state-of-the-art in accuracy and
      registration time.

PMID- 30094780
TI  - Access to Linguistically Appropriate Information for Blood and Marrow Transplant
      Patients: Results from Transplant Center Staff Survey.
AB  - Blood or marrow transplant (BMT) is a potentially curative treatment for numerous
      cancers and non-malignant disorders. BMT is a resource-intense treatment process,
      requiring patients to comprehend difficult health information and navigate a
      complex healthcare system. Linguistic and cultural barriers create additional
      challenges for patients with limited English proficiency (LEP) who may need
      translated information and interpretive services to make an informed decision
      about treatment. To identify information needs and gaps in language services for
      BMT patients with LEP, the National Marrow Donor Program(r) (NMDP)/Be The
      Match(r) administered a cross-sectional, web-based survey to 139 transplant
      centers (TCs) across the United States (U.S.). The survey yielded a 59% response
      rate. Findings show a significant need for translated patient education
      materials, especially in Spanish, Chinese, and Arabic, and practice gaps in the
      use of appropriate interpreters. Nearly one third of respondents indicated using
      family and friends to interpret for patients. The inability to locate educational
      resources in a specific language, lack of available bilingual staff, lack of a
      formal, centralized tracking system, and outdated tracking systems also pose
      significant barriers to meeting the language needs of BMT patients with LEP.

PMID- 30094781
TI  - How Does the Death Conscious Culture of Iran Affect Experiences of Depression?
AB  - This paper is divided into two parts. First I argue for the existence of a death
      conscious culture in Iran, traceable in religious and literary texts, and
      manifested strongly in the discourse following the Iran-Iraq war. I then look at
      how this culture influences articulations and experiences of depression as felt
      by Iranian patients. Adopting a phenomenological perspective and drawing on
      empirical data, I show how death-consciousness, as a point of cultural divergence
      between the UK and Iran, can be used to account for some of the
      phenomenologically significant cultural variations in the experience of
      depression. These include attitudes towards suicide, the significance of feelings
      of hopelessness, and the existence of a sense of absurdity among Iranian
      patients.

PMID- 30094782
TI  - Homeostatic balance of histone acetylation and deconstruction of repressive
      chromatin marker H3K9me3 during adipocyte differentiation of 3T3-L1 cells.
AB  - Background Adipocyte differentiation is completed by changing gene expression.
      Chromatin is closely related to gene expression. Therefore, its structure might
      be changed for adipocyte differentiation. Mouse 3T3-L1 preadipocytes have been
      used as a cell model to study molecular mechanisms of adipogenesis. Objective To
      examine changes of chromatin modification and expression of histone modifying
      enzymes during adipocyte differentiation. Methods Microscopic analysis and Oil
      Red O staining were performed to determine distinct phenotype of adipocyte
      differentiation. RT-PCR and Western blot analysis were used to examine expression
      levels of histone modifying enzymes during adipocyte differentiation. Histone
      modifications were examined by immunostaining analysis. Results Expression levels
      of P300 and cbp were increased during adipocyte differentiation. However,
      acetylation of histones was not quantitatively changed postdifferentiation of 3T3
      L1 cells compared to that at pre-differentiation. RT-PCR and Western blot
      analyses showed that expression levels of hdac2 and hdac3 were increased during
      adipocyte differentiation, suggesting histone acetylation at chromatin level was
      homeostatically controlled by increased expression of both HATs and HDACs. Tri
      methylation level of H3K9 (H3K9me3), but not that of H3K27me3, was significantly
      decreased during adipocyte differentiation. Decreased expression of setdb1 was
      consistent with reduced pattern of H3K9me3. Knock-down of setdb1 induced
      adipocyte differentiation. This suggests that setdb1 is a key chromatin modifier
      that modulates repressive chromatin. Conclusion These results suggest that there
      exist extensive mechanisms of chromatin modifications for homeostatic balance of
      chromatin acetylation and deconstruction of repressive chromatin during adipocyte
      differentiation.

PMID- 30094783
TI  - Adverse Drug Events Associated with sitagliptin Versus canagliflozin for the
      Treatment of Patients with Type 2 Diabetes Mellitus: A Systematic Comparison
      Through a Meta-Analysis.
AB  - INTRODUCTION: In this meta-analysis, we aimed to systematically compare the
      adverse drug events associated with sitagliptin (100 mg) versus canagliflozin 100
      or 300 mg in patients who were treated for type 2 diabetes mellitus (T2DM).
      METHODS: Online databases were searched for relevant studies comparing
      sitagliptin (100 mg) versus canagliflozin. Adverse drug events were considered as
      the clinical endpoints. The analysis was carried out by RevMan software whereby
      risk ratios (RR) and 95% confidence intervals (CI) were generated. RESULTS: Five
      studies with a total number of 2322 patients were included. When sitagliptin (100
      mg) was compared with canagliflozin (100 mg), the endpoints of any adverse
      events, adverse events leading to drug discontinuation, serious adverse events,
      urinary tract infections, hypoglycemia, and adverse events related to hypovolemia
      were not significantly different: (RR 1.10, 95% CI 1.00-1.21; P = 0.05), (RR
      1.20, 95% CI 0.67-2.16; P = 0.54), (RR 0.90, 95% CI 0.49-1.66; P = 0.73), (RR
      1.26, 95% CI 0.77-2.08; P = 0.36), (RR 1.01, 95% CI 0.30-3.43; P = 0.99), and (RR
      1.76, 95% CI 0.52-5.94; P = 0.36), respectively. However, canagliflozin was
      associated with increased genital mycotic infection (RR 4.32, 95% CI 2.11-8.83; P
      = 0.0001). When genital mycotic infections associated with sitagliptin versus
      canagliflozin were compared in male and female patients separately, the risk was
      still significantly higher with canagliflozin: (RR 7.00, 95% CI 2.44-20.06; P =
      0.003) and (RR 4.02, 95% CI 2.22-7.27; P = 0.00001), respectively. The same
      results were obtained when sitagliptin (100 mg) was compared to canagliflozin 300
      mg. CONCLUSIONS: Canagliflozin was associated with a significantly higher risk of
      genital mycotic infections when compared to sitagliptin. However, the other
      adverse drug events were similarly manifested when sitagliptin 100 mg was
      compared to either canagliflozin 100 or 300 mg.

PMID- 30094784
TI  - Current Level of Glycemic Control and Clinical Inertia in Subjects Using Insulin
      for the Treatment of Type 1 and Type 2 Diabetes in the Czech Republic and the
      Slovak Republic: Results of a Multinational, Multicenter, Observational Survey
      (DIAINFORM).
AB  - INTRODUCTION: The aim of the study was to determine the level of metabolic
      control in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)
      patients in the Czech and Slovak Republics. METHODS: A non-interventional
      prospective (observational) study was conducted from January 2015 until April
      2016 in routine clinical practice settings at 141 centers in the Czech and Slovak
      Republics. Data were analyzed from a total of 425 patients with T1DM and 1034
      patients with T2DM, proportionally corresponding to the number of patients in
      both countries. The primary objective of the study was to determine the
      percentage of patients with HbA1c < 7% (53 mmol/mol). RESULTS: Patients with
      T1DM: In this group of patients (55.8% males, mean age 45.9 +/- 14.83 years, BMI
      25.8 +/- 4.21 kg/m2, diabetes duration 12.1 +/- 9.44 years), 29.9% reached HbA1c
      levels < 53 mmol/mol. Patients with T2DM: In this group of patients (50.3% male,
      mean age 63.9 +/- 9.65 years, BMI 31.0 +/- 5.19 kg/m2, diabetes duration 12.4 +/-
      7.47 years, duration of insulin therapy 5.8 +/- 4.71 years), 33.4% reached HbA1c
      levels < 53 mmol/mol. CONCLUSION: The overall percentage of patients with HbA1c <
      53 mmol/mol in the T1DM group was 29.9% and in the T2DM group was 33.4%. Despite
      an increasing number of treatment options, most patients still fail to reach the
      recommended HbA1c targets. FUNDING: Sanofi, Czech Republic.

PMID- 30094785
TI  - Successful Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar
      Status in an Infant with KCNJ11-Related Neonatal Diabetes Mellitus via Continuous
      Renal Replacement Therapy.
AB  - Neonatal diabetes mellitus (NDM) is a rare monogenic disorder presenting as
      uncontrolled hyperglycemia during the first 6 months of life. Hyperglycemic
      hyperosmolar state (HHS) is quite rare in NDM patients, and reported experience
      with this condition is limited. Continuous renal replacement therapy (CRRT) is
      frequently used as a mode of dialytic treatment in critically ill patients with
      acute renal failure, but has seldom been used in patients with diabetic
      ketoacidosis (DKA) and HHS. We report the case of a 2-month-old infant admitted
      to our hospital presenting with dyspnea and lethargy. Blood gas showed severe
      hyperosmotic DKA. After 21 h of fluid and insulin therapy, the baby presented
      with increased drowsiness and irregular respiration, which suggested cerebral
      edema. Moreover, the DKA and HHS were exacerbated. After 18 h of CRRT, the
      patient gradually recovered from DKA and HHS. The gene analysis revealed a de
      novo mutation (c.602G > A (p.R201H)) of the KCNJ11 gene, and oral glibenclamide
      successfully replaced insulin treatment in the patient.

PMID- 30094788
TI  - Aniline-based catalysts as promising tools to improve analysis of carbonyl
      compounds through derivatization techniques: preliminary results using
      dansylacetamidooxyamine derivatization and LC-fluorescence.
AB  - Derivatization techniques based on alpha-effect amines and H+ catalysis are
      commonly used for the measurement of carbonyl compounds (CCs), whether in
      environmental, food, or biological samples. Here, we investigated the potential
      of aniline-based catalysts to improve derivatization rates of selected carbonyls
      by using dansylacetamidooxyamine (DNSAOA) as a reagent. Kinetic experiments were
      performed in aqueous solutions by varying catalyst and CC concentrations and
      delivered insights into the reaction mechanism. Using anilinium acetate (AnAc),
      rate constants varied linearly with the catalyst concentration with rate
      enhancements toward H+-catalyzed reactions as high as ca. 90 and 200 for acetone
      and benzaldehyde, respectively. Owing to contamination problems when using AnAc,
      anilinium chloride (AnCl) was chosen for the optimized analysis of real samples
      at low concentration. Rate enhancements for derivatization reaction of 4.4
      (methylglyoxal), 6.0 (glyoxal), 12 (acetone), 20 (formaldehyde), and 47
      (hydroxyacetaldehyde) were obtained using 0.1 M AnCl. The optimized method was
      successfully applied to the determination of the above compounds in natural snow
      and meltwater samples. Limits of detection (LODs) and limits of quantification
      (LOQs) were in the 2-14 and 7-41 nM range, respectively, i.e., low enough to
      allow for the analysis of most natural samples. Satisfactory relative recoveries
      (92.8 +/- 3.8-118.3 +/- 4.4%) and intra-day precision (2.7-11.3%) were achieved.
      Finally, we think that this approach could be applied not only to every alpha
      effect nitrogen reagent-with the most evident profit of lowering derivatization
      times and particularly those required for low-reactive ketones-but also to the
      derivatization of CCs onto coated solid sorbents.

PMID- 30094789
TI  - Probing some organic ukiyo-e Japanese pigments and mixtures using non-invasive
      and mobile infrared spectroscopies.
AB  - Non-invasive identification of organic colourants in paintings still remains a
      challenging issue, especially in the case of extremely thin layers of paint on
      printed paper such as Japanese ukiyo-e prints. Because prints are fragile
      artworks, various non-invasive analytical methods need to be employed. The
      present work focuses on results obtained by combining fibre optic reflectance
      spectroscopy in the near-infrared range (FORS NIR) with mid-infrared (MIR)
      spectroscopy. The first step consists of identifying spectroscopic marker bands
      typical of some organic pigments (indigo, gamboge, cochineal, turmeric,
      safflower, dragon's blood). Some reference printouts involving paper substrate,
      binder and pigments (seldom used or as mixtures) were then investigated in order
      to establish a straightforward way to extract the marker bands of the pigments.
      Some data post-treatments were applied to the spectra, such as spectral
      subtraction, in order to abstract the signal from overlapping bands originating
      from both substrate and binder, and second derivative calculation to emphasise
      the pigment marker bands' frequency positions. These data treatments turned out
      to be relevant to extract information on the organic pigments of interest, even
      within complex mixtures.

PMID- 30094787
TI  - Fluorescence polarization immunoassay for rapid screening of the pesticides
      thiabendazole and tetraconazole in wheat.
AB  - Fluorescence polarization immunoassays (FPIAs) for thiabendazole and
      tetraconazole were first developed. Tracers for FPIAs of thiabendazole and
      tetraconazole were synthesized and the tracers' structures were confirmed by HPLC
      MS/MS. The 4-aminomethylfluorescein-labeled tracers allowed achieving the best
      assay sensitivity and minimum reagent consumption in comparison with
      aminofluorescein-labeled and alkyldiaminefluoresceinthiocarbamyl-labeled tracers.
      Measurements of fluorescence polarization were performed using a portable device.
      The developed FPIA methods were applied for the analysis of wheat. Fast and
      simple sample preparation technique earlier developed by authors for pesticides
      was adapted for thiabendazole and tetraconazole. The limits of detection of
      thiabendazole and tetraconazole in wheat were 20 and 200 MUg/kg, and the lower
      limits of quantification were 40 and 600 MUg/kg, respectively. The recovery test
      was performed by two methods-FPIA and HPLC-MS/MS. The results obtained by FPIA
      correlated well with those obtained by HPLC-MS/MS (r2 = 0.9985 for thiabendazole,
      r2 = 0.9952 for tetraconazole). Average recoveries of thiabendazole and
      tetraconazole were 74 +/- 4% and 72 +/- 3% by FPIA, and average recoveries of
      thiabendazole and tetraconazole were 86 +/- 2% and 74 +/- 1% by HPLC-MS/MS (n =
      15). Graphical abstract ?.

PMID- 30094790
TI  - Longitudinal investigation of the metabolome of 3D aggregating brain cell
      cultures at different maturation stages by 1H HR-MAS NMR.
AB  - The aim of the present study was to establish the developmental profile of
      metabolic changes of 3D aggregating brain cell cultures by 1H high-resolution
      magic angle spinning (HR-MAS) NMR spectroscopy. The histotypic 3D brain
      aggregate, containing all brain cell types, is an excellent model for mechanistic
      studies including OMICS analysis; however, their metabolic profile has not been
      yet fully investigated. Chemometric analysis revealed a clear separation of
      samples from the different maturation time points. Metabolite concentration
      evolutions could be followed and revealed strong and various metabolic
      alterations. The strong metabolite evolution emphasizes the brain modeling
      complexity during maturation, possibly reflecting physiological processes of
      brain tissue development. The small observed intra- and inter-experimental
      variabilities show the robustness of the combination of 1H-HR-MAS NMR and 3D
      brain aggregates, making it useful to investigate mechanisms of toxicity that
      will ultimately contribute to improve predictive neurotoxicology. Graphical
      Abstract ?.

PMID- 30094792
TI  - Evaluation of safety and efficacy of p53MVA vaccine combined with pembrolizumab
      in patients with advanced solid cancers.
AB  - BACKGROUND: Vaccination of cancer patients with p53-expressing modified vaccinia
      Ankara virus (p53MVA) has shown in our previous studies to activate p53-reactive
      T cells in peripheral blood but without immediate clinical benefit. We
      hypothesized that the immunological responses to p53MVA vaccine may require
      additional immune checkpoint blockade to achieve clinically beneficial levels. We
      therefore conducted a phase I trial evaluating the combination of p53MVA and
      pembrolizumab (anti-PD-1) in patients with advanced solid tumors. PATIENTS AND
      METHODS: Eleven patients with advanced breast, pancreatic, hepatocellular, or
      head and neck cancer received up to 3 triweekly vaccines in combination with
      pembrolizumab given concurrently and thereafter, alone at 3-week intervals until
      disease progression. The patients were assessed for toxicity and clinical
      response. Correlative studies analyzed p53-reactive T cells and profile of immune
      function gene expression. RESULTS: We observed clinical responses in 3/11
      patients who remained with stable disease for 30, 32, and 49 weeks. Two of these
      patients showed increased frequencies and persistence of p53-reactive CD8+ T
      cells and elevation of expression of multiple immune response genes. Borderline
      or undetectable p53-specific T cell responses in 7/11 patients were related to no
      immediate clinical benefit. The first study patient had a grade 5 fatal
      myocarditis. After the study was amended for enhanced cardiac monitoring, no
      additional cardiac toxicities were noted. CONCLUSION: We have shown that the
      combination of p53MVA vaccine with pembrolizumab is feasible, safe, and may offer
      clinical benefit in select group of patients that should be identified through
      further studies.

PMID- 30094791
TI  - Fractionation of cadmium in tobacco and cigarette smoke condensate using XANES
      and sequential leaching with ICP-MS/MS.
AB  - Fractionation data for cadmium in tobacco products, as obtained by sequential
      leaching of cadmium species with ICP-MS/MS analysis, and separately by X-ray
      absorption near edge structure (XANES) are presented here for the first time. The
      total amount of cadmium found in 3R4F cigarette cut tobacco was 1526 +/- 42 MUg
      kg-1, of which 5% was found in the smoke under ISO smoking conditions. XANES
      analysis showed that Cd in tobacco, cigarette smoke and ash was present in the +
      2 oxidation state. Examination of the gas-particle partitioning of smoke cadmium
      suggests that Cd in mainstream smoke is best viewed as semi-volatile, existing in
      both particulate and gas phases. Sequential extraction of trapped tobacco smoke
      was carried out to get a deeper insight into the chemistry of cigarette smoke
      cadmium compounds. Consecutive extractions with ultrapure water, dilute (1%)
      nitric acid and 10% nitric acid led to extraction of a total amount of Cd which
      agreed with that obtained after microwave digestion of the whole sample,
      suggesting that cadmium was quantitatively leachable into aqueous/acidic
      solutions. Most Cd (~ 90% of the total Cd in the smoke condensate) was extracted
      into dilute nitric acid (likely as CdO, Cd(OH)2 and CdCO3) with a minor
      percentage (3%) extracted into water (likely as CdCl2) and in 10% nitric acid
      (likely as CdS). Extraction of trapped mainstream smoke with pentane, followed by
      ICP-MS/MS analysis, to examine the possible presence of organocadmium in 3R4F
      tobacco smoke, did not show the presence of organocadmium compounds above the
      method LOQ (2 MUg kg-1), possibly due to their reactivity under the experimental
      conditions. The high selectivity with sufficient sensitivity achieved by ICP
      MS/MS was invaluable to quantify Cd (at low MUg kg-1levels) simultaneously with
      sulphur and chlorine in the tobacco smoke fractions of complex matrix. The
      cadmium chemistry in the smoke, identified in this study, is consistent with both
      relatively high lung absorption and DNA binding; both potentially important
      factors for disease progression in smokers. Graphical Abstract This paper
      provides quantitative fractionation data for cadmium in tobacco and smoke by
      using sequential leaching with ICPMS and XANES.

PMID- 30094793
TI  - Active study: undetected prevalence and clinical inertia in the treatment of
      breakthrough cancer pain (BTcP).
AB  - AIMS: To prove if there is clinical inertia in the identification and treatment
      of episodes of breakthrough cancer pain (BTcP), comparing actual results from
      clinical practice with clinical oncologists' prior perception. DESIGN:
      Observational and descriptive study, using information collected by practising
      medical oncologists, at three moments: (a) questionnaire regarding their
      professional judgement of the handling of patients with BTcP in their practice,
      (b) cross-sectional clinical screening, to detect possible existing cases of BTcP
      in a representative sample of their patients, (c) retrospective self-audit of
      clinical case histories of patients diagnosed with BTcP to find out about how it
      has been handled. PARTICIPANTS AND STUDY PERIOD: A random sample on a state level
      of 108 specialists in medical oncology. 540 patients who suffer some type of
      cancer pain on the designated study date for each specialist (July-December
      2016). RESULTS: The global prevalence of BTcP in the study sample covered 91.3%
      of the patients who were suffering some type of cancer pain. Barely 2% of the
      doctors surveyed suspected figures around this mark. 40.9% of the cases had not
      been previously detected as BTcP by their doctors. Although 90% of the patients
      who had previously been diagnosed with BTcP received a specific analgesic
      treatment for the symptoms, 42% of those patients with known BTcP were not able
      to control their episodes of pain. CONCLUSIONS: Clinical inertia is a serious
      problem in the handling of BTcP in medical oncology services, where it is the
      subject of a significantly low level of detection and treatment, despite the
      contrasting perception of specialists.

PMID- 30094786
TI  - Mass spectrometry-based shotgun lipidomics - a critical review from the technical
      point of view.
AB  - Over the past decade, mass spectrometry (MS)-based "shotgun lipidomics" has
      emerged as a powerful tool for quantitative and qualitative analysis of the
      complex lipids in the biological system. The aim of this critical review is to
      give the interested reader a concise overview of the current state of the
      technology, focused on lipidomic analysis by mass spectrometry. The pros and
      cons, and pitfalls associated with each available "shotgun lipidomics" method are
      discussed; and the new strategies for improving the current methods are
      described. A list of important papers and reviews that are sufficient rather than
      comprehensive, covering all the aspects of lipidomics including the workflow,
      methodology, and fundamentals is also compiled for readers to follow. Graphical
      abstract ?.

PMID- 30094795
TI  - Ventilator Weaning: How Far from the Final Quantum Leap?

PMID- 30094796
TI  - Bioaccumulation process and health risk assessment of toxic elements in tomato
      fruit grown under Zn nutrition treatment.
AB  - The aim of this work was to determine elements composition and bioaccumulation
      process in ripe tomato fruits influenced by zinc feeding of plants which was
      applied in three different doses. Macro- and microelement content in growing
      soil, seeds, and fruits was determined by ICP-OES method. Health risk assessment
      was calculated according to the presence of some toxic elements. It was found
      that predominant macroelements were phosphorus, potassium, calcium, and magnesium
      followed by other ten determined elements. The presence of five potentially toxic
      elements (cadmium, chromium, lead, nickel, and strontium) in seed and fruits was
      detected. Bioaccumulation differences (especially in case of potassium) for some
      elements in seed and fruit were established. In both cases, calcium and lead were
      the only elements with antagonistic effect towards zinc feeding process. Health
      risk assessment has shown that acute risk is low for all toxic elements
      (according to acute hazard quotient (HQ) calculation) except for cadmium in fruit
      seed, where it can be characterized as moderate. Long-term hazard quotient
      calculation showed moderate risk in the case of lead (fruit skin and seed) and
      low values for other toxic elements. Since the most part of toxic elements was
      accumulated in tomato fruit skin and seed, peeling of fruits can significantly
      reduce health risk. Graphical abstract ?.

PMID- 30094794
TI  - Transient Receptor Potential Channels and Chronic Airway Inflammatory Diseases: A
      Comprehensive Review.
AB  - Chronic airway inflammatory diseases remain a major problem worldwide, such that
      there is a need for additional therapeutic targets and novel drugs. Transient
      receptor potential (TRP) channels are a group of non-selective cation channels
      expressed throughout the body that are regulated by various stimuli. TRP channels
      have been identified in numerous cell types in the respiratory tract, including
      sensory neurons, airway epithelial cells, airway smooth muscle cells, and
      fibroblasts. Different types of TRP channels induce cough in sensory neurons via
      the vagus nerve. Permeability and cytokine production are also regulated by TRP
      channels in airway epithelial cells, and these channels also contribute to the
      modulation of bronchoconstriction. TRP channels may cooperate with other TRP
      channels, or act in concert with calcium-dependent potassium channels and calcium
      activated chloride channel. Hence, TRP channels could be the potential
      therapeutic targets for chronic airway inflammatory diseases. In this review, we
      aim to discuss the expression profiles and physiological functions of TRP
      channels in the airway, and the roles they play in chronic airway inflammatory
      diseases.

PMID- 30094800
TI  - Author's Reply to Goulet: Comment on: "Drinking Strategies: Planned Drinking
      Versus Drinking to Thirst''.

PMID- 30094797
TI  - Physical Activity Questionnaires for Pregnancy: A Systematic Review of
      Measurement Properties.
AB  - BACKGROUND: In order to assess physical activity (PA) during pregnancy, it is
      important to choose the instrument with the best measurement properties.
      OBJECTIVES: To systematically summarize, appraise, and compare the measurement
      properties of all self-administered questionnaires assessing PA in pregnancy.
      METHODS: We searched PubMed, Embase, and SPORTDiscus with the following inclusion
      criteria: (i) the study reported at least one measurement property (reliability,
      criterion validity, construct validity, responsiveness) of a self-administered
      questionnaire; (ii) the questionnaire intended to measure PA; (iii) the
      questionnaire was evaluated in healthy pregnant women; and (iv) the study was
      published in English. We evaluated results, quality of individual studies, and
      quality of evidence using a standardized checklist (Quality Assessment of
      Physical Activity Questionnaires [QAPAQ]) and the GRADE (Grading of
      Recommendation, Assessment, Development, and Evaluation) approach. RESULTS:
      Seventeen articles, reporting 18 studies of 11 different PA questionnaires (17
      versions), were included. Most questionnaire versions showed insufficient
      measurement properties. Only the French and Turkish versions of the Pregnancy
      Physical Activity Questionnaire (PPAQ) showed both sufficient reliability and
      construct validity. However, all versions of the PPAQ pooled together showed
      insufficient construct validity. The quality of individual studies was usually
      high for reliability but varied considerably for construct validity. Overall, the
      quality of evidence was very low to moderate. CONCLUSIONS: We recommend the PPAQ
      to assess PA in pregnancy, although the pooled results revealed insufficient
      construct validity. The lack of appropriate standards in data collection and
      processing criteria for objective devices in measuring PA during pregnancy
      attenuates the quality of evidence. Therefore, research on the validity of
      comparison instruments in pregnancy followed by consensus on validation reference
      criteria and standards of PA measurement is needed.

PMID- 30094798
TI  - Correction to: The Effect of Acute Caffeine Ingestion on Endurance Performance: A
      Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: Caffeine is a widely used ergogenic aid with most research
      suggesting it confers the greatest effects during endurance activities. Despite
      the growing body of literature around the use of caffeine as an ergogenic aid,
      there are few recent meta-analyses which quantitatively assess the effect of
      caffeine on endurance exercise. OBJECTIVES: To summarise studies which have
      investigated the ergogenic effects of caffeine on endurance time-trial
      performance and to quantitatively analyse the results of these studies to gain a
      better understanding of the magnitude of caffeine's ergogenic effect on endurance
      time-trial performance. METHODS: A systematic review was carried out on
      randomised placebo-controlled studies investigating the effects of caffeine on
      endurance performance and a meta-analysis was conducted to determine the
      ergogenic effect of caffeine on endurance time-trial performance. RESULTS: 44
      studies met the inclusion criteria and were included in the meta-analysis.
      Caffeine has a small but evident effect on endurance performance when taken in
      moderate doses (3-6 mg.kg-1) as well as an overall improvement following caffeine
      compared to placebo in mean power output (2.92 +/- 2.18%; Effect Size = 0.22 +/-
      0.15) and time-trial completion time (2.26 +/- 2.60%; Effect Size = 0.28 +/-
      0.12). However, differences in responses to caffeine ingestion have been shown,
      with two studies reporting slower time-trial performance while five studies
      reported lower mean power output during the time-trial. Caffeine can be used
      effectively as an ergogenic aid when taken in moderate doses, such as during
      sports when a small increase in endurance performance can lead to significant
      differences in placements as athletes are often separated by small margins.

PMID- 30094801
TI  - Comment on "Drinking Strategies: Planned Drinking Versus Drinking to Thirst''.

PMID- 30094802
TI  - On the link between phenomenal causality and personality dominance.
AB  - The present study investigated whether personality dominance is related to
      phenomenal causality. Recently, renewed attention has been given to dispositional
      theories, suggesting that the causal impression arises because people interpret
      collisions in terms of antagonistic action roles. Here, we examined the relation
      between personality dominance and the judgment of causality of ambiguous patterns
      of motion. The results revealed that dominance as a trait is associated with an
      increased tendency to infer causality in ambiguous displays. We found that
      participants with high dominance scores (measured by means of a questionnaire)
      gave significantly more causal judgments than participants with low dominance
      scores. Our findings highlight that people's understanding of causality is
      grounded in their experiences of action.

PMID- 30094799
TI  - The Effect of Angle and Velocity on Change of Direction Biomechanics: An Angle
      Velocity Trade-Off.
AB  - Changes of direction (CODs) are key manoeuvres linked to decisive moments in
      sport and are also key actions associated with lower limb injuries. During sport
      athletes perform a diverse range of CODs, from various approach velocities and
      angles, thus the ability to change direction safely and quickly is of great
      interest. To our knowledge, a comprehensive review examining the influence of
      angle and velocity on change of direction (COD) biomechanics does not exist.
      Findings of previous research indicate the biomechanical demands of CODs are
      'angle' and 'velocity' dependent and are both critical factors that affect the
      technical execution of directional changes, deceleration and reacceleration
      requirements, knee joint loading, and lower limb muscle activity. Thus, these two
      factors regulate the progression and regression in COD intensity. Specifically,
      faster and sharper CODs elevate the relative risk of injury due to the greater
      associative knee joint loading; however, faster and sharper directional changes
      are key manoeuvres for successful performance in multidirectional sport, which
      subsequently creates a 'performance-injury conflict' for practitioners and
      athletes. This conflict, however, may be mediated by an athlete's physical
      capacity (i.e. ability to rapidly produce force and neuromuscular control).
      Furthermore, an 'angle-velocity trade-off' exists during CODs, whereby faster
      approaches compromise the execution of the intended COD; this is influenced by an
      athlete's physical capacity. Therefore, practitioners and researchers should
      acknowledge and understand the implications of angle and velocity on COD
      biomechanics when: (1) interpreting biomechanical research; (2) coaching COD
      technique; (3) designing and prescribing COD training and injury reduction
      programs; (4) conditioning athletes to tolerate the physical demands of
      directional changes; (5) screening COD technique; and (6) progressing and
      regressing COD intensity, specifically when working with novice or previously
      injured athletes rehabilitating from an injury.

PMID- 30094803
TI  - Visual attention and its intimate links to spatial cognition.
AB  - It is almost universal to regard attention as the facility that permits an agent,
      human or machine, to give priority processing resources to relevant stimuli while
      ignoring the irrelevant. The reality of how this might manifest itself throughout
      all the forms of perceptual and cognitive processes possessed by humans, however,
      is not as clear. Here, we examine this reality with a broad perspective in order
      to highlight the myriad ways that attentional processes impact both perception
      and cognition. The paper concludes by showing two real-world problems that
      exhibit sufficient complexity to illustrate the ways in which attention and
      cognition connect. These then point to new avenues of research that might
      illuminate the overall cognitive architecture of spatial cognition.

PMID- 30094805
TI  - Systemic Inflammation Changes the Site of RAGE Expression from Endothelial Cells
      to Neurons in Different Brain Areas.
AB  - The receptor for advanced glycation endproducts (RAGE) is a transmembrane,
      immunoglobulin-like receptor that interacts with a broad repertoire of
      extracellular ligands. RAGE belongs to a family of cell adhesion molecules and is
      considered a key receptor in the inflammation axis and a potential contributor to
      the neurodegeneration. The present study aimed to investigate the content and
      cell localization of RAGE in the brain of Wistar rats subjected to systemic
      inflammation induced by a single dose of lipopolysaccharide (LPS, 5 mg/kg, i.p.).
      Fifteen days after LPS administration, the content of RAGE was analyzed in the
      prefrontal cortex (PFC), hippocampus (HIPP), cerebellum (CB), and substantia
      nigra (SN) were investigated. RAGE levels increased in all structures, except
      HIPP; however, immunohistochemistry analysis demonstrated that the cell site of
      RAGE expression changed from blood vessel-like structures to neuronal cells in
      all brain areas. Besides, the highest level of RAGE expression was found in SN.
      Immunofluorescence analysis in SN confirmed that RAGE expression was mainly co
      localized in endothelial cells (RAGE/PECAM-1 co-staining) in untreated animals,
      while LPS-treated animals had RAGE expression predominantly in dopaminergic
      neurons (RAGE/TH co-staining). Decreased TH levels, as well as increased pro
      inflammatory markers (TNF-alpha, IL-1beta, Iba-1, GFAP, and phosphorylated
      ERK1/2) in SN, occurred concomitantly to RAGE stimulation in the same site. These
      results suggest a role for RAGE in the establishment of a neuroinflammation
      neurodegeneration axis that develops as a long-term response to systemic
      inflammation by LPS.

PMID- 30094804
TI  - High methionine, low folate and low vitamin B6/B12 (HM-LF-LV) diet causes
      neurodegeneration and subsequent short-term memory loss.
AB  - Methionine is an essential amino acid found in rich quantities in average
      American diet such as meats, fish and eggs. Excessive consumption of such food
      often exceeds the normal requirement of the methionine in our body; which found
      to be related to the development of neurodegenerative disorders. However, the
      mechanistic pathways of methionine's influence on the brain are unclear. The
      present study is focus on the effects of high methionine, low folate and low
      vitamin B6/B12 (HM-LF-LV) diet on the dysfunction of neuronal and vascular
      specific markers in the brain. C57BL6/J male mice (8-10 week old) were fed with
      HM-LF-LV diet for a 6 week period. Cognitive function of mice was determine by
      measuring short-term memory using a Novel Object Recognition test (NORT).
      Neuronal dysfunction were evaluate by measuring the levels of Neuronal nuclear
      antigen (NeuN), Neuron-specific-enolase (NSE) and Fluoro-jade C(FJC)
      fluorescence; while cerebrovascular disruption were evaluate by assessing levels
      of endothelial junction proteins Vascular Endothelial-Cadherin (VE-Cadherin) and
      Claudin-5 in harvested brain tissue. Cerebrovascular permeability was assess by
      evaluating microvascular leakage of fluorescently labeled albumin in vivo.
      Endothelial and Neuronal Nitric Oxide Synthase (eNOS, nNOS) regulation and
      vascular inflammation (ICAM: intercellular adhesion molecules) were also evaluate
      in brain tissue. All assessments were conduct at weekly intervals throughout the
      study duration. NORT showed a significant temporal decrease in short-term memory
      of mice fed on HM-LF-LV diet for 6 weeks compared to the wild-type control group.
      Our experimental data showed that neuronal dysfunction (decreased NeuN levels and
      increased FJC positive neurons in brain) was more prominent in HM-LF-LV diet fed
      mice compared to normal diet fed control mice. In experimental mice,
      cerebrovascular disruption was found to be elevated as evident from increased
      pial venular permeability (microvascular leakage) and decreased in VE-Cadherin
      expression compared to control. Slight decrease in nNOS and increase in eNOS in
      experimental mice suggest a trend towards the decrease in potential for neuronal
      development due to the long-term HM-LF-LV diet fed. Collectively, our results
      suggest that a diet containing high methionine, low folate and low vitamin B6/B12
      results in increased neuronal degeneration and vascular dysfunction, leading to
      short-term memory loss. Interestingly, significant neuronal damage precedes
      vascular dysfunction.

PMID- 30094806
TI  - The Impact of Moving from EQ-5D-3L to -5L in NICE Technology Appraisals.
AB  - BACKGROUND: The EuroQol-5 Dimension (EQ-5D) instrument is the National Institute
      for Health and Care Excellence (NICE)'s preferred measure of health-related
      quality of life (QoL) in adults. The three-level (3L) value set is currently
      recommended for use, but the five-level (5L) set is increasingly being used in
      practice. OBJECTIVE: We aimed to explore the impact of moving from 3L to 5L in
      NICE appraisals. METHODS: We adapted our existing mapping for use with health
      state utility values derived from a population where the original distribution of
      utilities was unknown. We used this mapping to estimate 5L utilities for 21
      comparisons of interventions from models used in NICE technology appraisal
      decision making, covering a range of disease areas. RESULTS: All utilities
      increased using 5L, and the differences between highest and lowest utilities
      decreased. In ten oncology comparisons, using 5L generally increased the
      incremental quality-adjusted life-years (QALYs) as the benefit from improving
      survival increased. In four non-oncology comparisons where the intervention
      improved QoL only, the incremental QALYs decreased as the benefit of improving
      QoL was reduced. In seven non-oncology comparisons where interventions improved
      survival and QoL, there was a trade-off between increasing the benefit from
      survival and decreasing the benefit from improving QoL. CONCLUSION: 3L and 5L
      lead to substantially different estimates of incremental QALYs and cost
      effectiveness. The direction and magnitude of the change is not consistent across
      case studies. Using 5L instead of 3L may lead to different reimbursement
      decisions. NICE will face inconsistencies in decision making if it uses 3L and 5L
      concurrently.

PMID- 30094807
TI  - Comment on: Sensitivity Analysis for Not-at-Random Missing Data in Trial-Based
      Cost-Effectiveness Analysis: A Tutorial.

PMID- 30094808
TI  - Regulatory Frameworks in Times of Uncertainty.
AB  - Patient and public expectations on access to new types of medicines has changed
      the role of the regulator in granting marketing authorizations. Whether current
      regulatory frameworks can accommodate further advances in biomedical science
      remains a challenge, but suggestions are made as to how this may be possible.

PMID- 30094810
TI  - A Randomized Clinical Trial of Wheeled Mobility for Pressure Injury Prevention
      and Better Function.
AB  - OBJECTIVES: To evaluate the effectiveness of wheelchair assessment and
      configuration on pressure injury incidence, mobility, and functioning in a
      wheelchair. DESIGN: Randomized controlled trial with participants individually
      randomized into intervention and control groups. SETTING: Nursing home.
      PARTICIPANTS: Nursing home residents aged 60 and older who used wheelchairs and
      were at risk for pressure injuries (N=258). INTERVENTION: Treatment and
      evaluation, individually configured wheelchair and skin protection cushion;
      control and evaluation, facility-provided wheelchair and skin protection cushion.
      MEASUREMENTS: Pressure injury incidence, Nursing Home Life Space Diameter score,
      Functioning Every Day in a Wheelchair-Capacity (FEW-C) score, and Wheelchair
      Skills Test (WST) score. RESULTS: No differences in pressure injuries (p=.77)
      were found. Pelvic rotation (odds ratio (OR)=0.15, 95% confidence interval
      (CI)=0.03-0.70, p=.02) and Day 14 WST skill score (OR=0.74, 95% CI=0.60-0.91,
      p=.004) were significant predictors of pressure injuries. Significant differences
      were observed between groups in change in FEW-C independence scores between
      before randomization and endpoint (p=.03) and before randomization and 14 days
      (p=.04). CONCLUSION: Participants with individually configured wheelchairs
      improved more in the safe and effective use of their wheelchairs than residents
      with facility-provided wheelchairs. The outcomes indicated that nursing home
      residents functioned safely at a higher level in their wheelchairs if their
      devices were individually configured using a comprehensive wheelchair and seating
      assessment process. There was no difference in the incidence of pressure injuries
      between the two groups. TRIAL REGISTRATION: NCT01275313.

PMID- 30094809
TI  - Improving the ED-to-Home Transition: The Community Paramedic-Delivered Care
      Transitions Intervention-Preliminary Findings.
AB  - OBJECTIVES: To describe a novel model of care that uses community-based
      paramedics to deliver a modified version of the evidence-based hospital-to-home
      Care Transitions Intervention (CTI) to a new context: the emergency department
      (ED)-to-home transition. DESIGN: Single-blind randomized controlled trial.
      SETTING: Three EDs in 2 cities. PARTICIPANTS: Through June 2017, 422 individuals
      discharged home from the EDs who provided consent and were randomized to receive
      the modified CTI. INTERVENTION: We modified the hospital-to-home CTI, applying it
      to the ED-to-home transition and delivering services through community
      paramedics, allowing the program to benefit from the unique attributes of
      paramedics to deliver care. MEASUREMENTS: Through surveys of participants,
      medical record review, and documentation of activities by CTI coaches, we
      characterize the participants and program, including feasibility and
      acceptability. RESULTS: Median age of participants was 70.7, 241 (57.1%) were
      female, and 385 (91.2%) were white. Coaches successfully completed 354 (83.9%)
      home visits and 92.7% of planned telephone follow-up for call 1, 90.9% for call
      2, and 85.8% for call 3. We found high levels of acceptability among
      participants, with most participants (76.2%) and their caregivers (83.1%)
      reporting themselves likely or extremely likely to choose an ED featuring the CTI
      program in the future. Coaches reported delivering expected services during
      contact at least 88% of the time. CONCLUSION: Although final conclusions about
      program effectiveness must await the results of the randomized controlled trial,
      the findings reported here are promising and provide preliminary support for an
      ED-to-home CTI Program's ability to improve outcomes. The coaches' identity as
      community paramedics is particularly noteworthy, because this is a unique role
      for this provider type. J Am Geriatr Soc 66:2213-2220, 2018.

PMID- 30094811
TI  - Orthostatic intolerance in enhanced recovery laparoscopic colorectal resection.
AB  - BACKGROUND: Orthostatic hypotension (OH) and intolerance (OI) are common findings
      in the early postoperative period after major surgery and may delay early
      mobilization. The mechanism of impaired orthostatic competence and OI symptoms is
      not fully understood, and specific data after colorectal surgery with well
      defined perioperative care regimens and mobilization protocols are lacking. The
      aim of this study was to investigate the prevalence, possible risk factors and
      the impact of OI in patients undergoing elective minimal invasive colorectal
      cancer resection. METHODS: A prospective single-centre study with an optimal
      enhanced recovery program and multimodal analgesic treatment. OI and OH were
      evaluated using a well-defined mobilization protocol preoperatively and 6 hour
      and 24 hour postoperatively. RESULTS: A total of 100 patients were included in
      the data analysis. The overall median length of stay was 3 days (1-38). OI was
      observed in 53% of the patients 6 hour postoperatively and in 24% at 24 hour. OI
      at 6 hour postoperatively was associated with younger age, lower BMI, and female
      gender. At 24 hour postoperatively, female gender and ASA class >1 was associated
      with OI. Opioid consumption and intravenous fluid during the first 24 hour was
      not associated with OI. Postoperative complications were equally observed between
      patients with and without OI. Although not statistically significant, patients
      with OI at 24 hour postoperatively had prolonged LOS (mean 4.0 vs 7.5 days, P =
      0.069) compared with patients without OI. CONCLUSION: Postoperative orthostatic
      intolerance is a common problem during the first 24 hour following laparoscopic
      colorectal resection and may be followed by delayed recovery.

PMID- 30094812
TI  - Does your mindfulness benefit others? A systematic review and meta-analysis of
      the link between mindfulness and prosocial behaviour.
AB  - Mindfulness-based meditation practices have received substantial scientific
      attention in recent years. Mindfulness has been shown to bring many psychological
      benefits to the individual, but much less is known about whether these benefits
      extend to others. This meta-analysis reviewed the link between mindfulness - as
      both a personality variable and an intervention - and prosocial behaviour. A
      literature search produced 31 eligible studies (N = 17,241) and 73 effect sizes.
      Meta-analyses were conducted using mixed-effects structural equation models to
      examine pooled effects and potential moderators of these effects. We found a
      positive pooled effect between mindfulness and prosocial behaviour for both
      correlational (d = .73 CI 95% [0.51 to 0.96]) and intervention studies (d = .51
      CI 95% [0.37 to 0.66]). For the latter, medium-sized effects were obtained across
      varying meditation types and intensities, and across gender and age categories.
      Preliminary evidence is presented regarding potential mediators of these effects.
      Although we found that mindfulness is positively related to prosociality, further
      research is needed to examine the mediators of this link and the contexts in
      which it is most pronounced.

PMID- 30094813
TI  - No Evidence of a Causal Role of Antiepileptic Drug Treatment with Regard to the
      Development of Dementia.

PMID- 30094814
TI  - Association Between Frailty and Elder Abuse in Community-Dwelling Older Adults in
      Mexico City.
AB  - OBJECTIVES: To investigate the association between frailty and elder abuse in
      community-dwelling older adults. DESIGN: Secondary cross-sectional analysis of a
      prospective cohort. SETTING: The Frailty, Dynapenia and Sarcopenia in Mexican
      Adults study, a cohort of community-dwelling adults from 2 municipalities in
      Mexico City. PARTICIPANTS: Community-dwelling adults aged 60 and older (N=487,
      mean age 73.2 +/- 8.0, 80% female). MEASUREMENTS: Elder abuse was assessed using
      the Geriatric Mistreatment Scale and frailty using the Frailty Phenotype. Abuse
      was then classified as total abuse (any subtype), conflict abuse (physical,
      psychological, sexual abuse), financial abuse, and caregiver neglect. Information
      was also obtained on sociodemographic characteristics, comorbidities, mental
      status, nutritional status, disability, and polypharmacy. RESULTS: Prevalence of
      total abuse was 35.7%. Frailty was associated with total abuse (odds ratio
      (OR)=2.52, 95% confidence interval (CI)=1.22-5.21, p=.01) and conflict abuse
      (OR=2.50, 95% CI=1.18-5.33, p=.02) after adjusting for confounders but not with
      financial abuse or caregiver neglect. Depression was an effect modifier in the
      association between frailty and total abuse. Frailty was associated with total
      abuse in participants with depression (OR=5.23, 95% CI=1.87-14.56, p=.002) but
      not in those without (OR=0.55, 95% CI=0.10-2.87, p=.47). CONCLUSION: Frailty is
      associated with total and conflict abuse in community-dwelling older adults.
      Further studies are needed to elucidate the effect of frailty on elder abuse and
      investigate the effectiveness of interventions for primary and secondary
      prevention.

PMID- 30094815
TI  - Surrogate Endpoints in Pediatric Studies Submitted to the US FDA.
AB  - The 21st Century Cures Act was passed in December, 2016, and included a number of
      provisions to facilitate drug approval. Considerable discussion was generated
      related to some aspects of the Act, especially to the use of surrogate endpoints
      (SEs) as a means to shorten the time required prior to receiving US Food and Drug
      Administration (FDA) approval.1 The objective of this analysis was to identify
      the use and outcomes of SEs and clinical endpoints in pediatric drug development
      trials.

PMID- 30094816
TI  - Frailty and Resilience as Outcome Measures in Clinical Trials and Geriatric Care:
      Are We Getting Any Closer?

PMID- 30094819
TI  - Identifying Risk of Sleep Apnea and Major Hospital Events in an Older Inpatient
      Population.

PMID- 30094817
TI  - A Composite Measure of Caregiver Burden in Dementia: The Dementia Burden Scale
      Caregiver.
AB  - OBJECTIVES: To better capture the scope of caregiver burden by creating a
      composite of 3 existing measures that assess different health domains. DESIGN:
      Prospective follow-up study. SETTING: University-based dementia care management
      program. PARTICIPANTS: Caregivers of persons with dementia (PWD) (N=1,091).
      MEASUREMENTS: The composite measure (the Dementia Burden Scale-Caregiver (DBS
      CG)) was based on the Modified Caregiver Strain Index, Neuropsychiatric Inventory
      Questionnaire Distress Scale, and Patient Health Questionnaire (PHQ-9).
      Alternative factor structures were evaluated using 2 confirmatory factor analysis
      (CFA) models: a bifactor model and a 3 correlated factors model. Good model fit
      was defined as a root mean square error of approximation (RMSEA) of less than
      0.06 and comparative fit index (CFI) value greater than 0.95. Coefficient omega
      was used to estimate scale reliability. Minimally important differences (MIDs)
      were estimated by anchoring the magnitude of DBS-CG change to change in caregiver
      self-efficacy and functional ability of PWD. RESULTS: The bifactor CFA model fit
      best (RMSEA = 0.04, CFI = 0.95). Based on this model, a DBS-CG scale was created
      wherein all items were transformed to a possible range of 0 to 100 and then
      averaged. Higher scores indicate higher burden. Mean DBS-CG score was 27.3. The
      reliability was excellent (coefficient omega=0.93). MID estimates ranged from 4
      to 5 points (effect sizes: 0.20-0.49). CONCLUSION: This study provides support
      for the reliability and validity of the DBS-CG. It can be used as an outcome
      measure to assess the effect of interventions to reduce dementia caregiver
      burden.

PMID- 30094818
TI  - Degree of Implementation of the Interventions to Reduce Acute Care Transfers
      (INTERACT) Quality Improvement Program Associated with Number of
      Hospitalizations.
AB  - OBJECTIVES: To determine whether degree of implementation of the Interventions to
      Reduce Acute Care Transfers (INTERACT) program is associated with number of
      hospitalizations and emergency department (ED) visits of skilled nursing facility
      (SNF) residents. DESIGN: Secondary analysis from a randomized controlled trial.
      SETTING: SNFs from across the United States (N=264). PARTICIPANTS: Two hundred of
      the SNFs from the randomized trial that provided baseline and intervention data
      on INTERACT use. INTERVENTIONS: During a 12-month period, intervention SNFs
      received remote training and support for INTERACT implementation; control SNFs
      did not, although most control facilities were using various components of the
      INTERACT program before and during the trial on their own. MEASUREMENTS: INTERACT
      use data were based on monthly self-reports for SNFs randomized to the
      intervention group and pre- and postintervention surveys for control SNFs.
      Primary outcomes were rates of all-cause hospitalizations, potentially avoidable
      hospitalizations (PAHs), ED visits without admission, and 30-day hospital
      readmissions. RESULTS: The 65 SNFs (32 intervention, 33 control) that reported
      increases in INTERACT use had reductions in all-cause hospitalizations (0.427 per
      1,000 resident-days; 11.2% relative reduction from baseline, p<.001) and PAHs
      (0.221 per 1,000 resident-days; 18.9% relative reduction, p<.001). The 34 SNFs
      (12 intervention, 22 control) that reported consistently low or moderate INTERACT
      use had statistically insignificant changes in hospitalizations and ED visit
      rates. CONCLUSION: Increased reported use of core INTERACT tools was associated
      with significantly greater reductions in all-cause hospitalizations and PAHs in
      both intervention and control SNFs, suggesting that motivation and incentives to
      reduce hospitalizations were more important than the training and support
      provided in the trial in improving outcomes. Further research is needed to better
      understand the most effective strategies to motivate SNFs to implement and
      sustain quality improvement programs such as INTERACT.

PMID- 30094820
TI  - Replacement of Urinary Catheter for Urinary Tract Infections: A Prospective
      Observational Study.
AB  - OBJECTIVES: To assess whether catheter replacement is associated with better
      clinical outcomes in individuals with long-term urinary catheters. DESIGN:
      Prospective, noninterventional study. PARTICIPANTS: Individuals (mean age 79.2+/
      11.5) who had had an indwelling urinary catheter for longer than 7 days and a
      symptomatic urinary tract infection (UTI) (N=315). MEASUREMENTS: The exposure
      assessed was replacement of the indwelling urinary catheter within 6 hours. The
      primary outcome was clinical failure at day 7. We developed a propensity score
      model for catheter replacement to match participants. Multivariate analysis was
      conducted to adjust for other risk factors. RESULTS: The catheter was replaced in
      98 participants and not in 217. More than half of the participants resided in
      long-term care facilities and had high Charlson comorbidity scores. The rate of
      clinical failure on day 7 was 35.2% (108/306). The 30-day fatality rate was 30.8%
      (96/315). We found no statistically significant association between catheter
      replacement and clinical failure (propensity-adjusted odds ratio (OR)=0.90, 95%
      CI=0.50-1.63) or 30-day fatality (OR=0.76, 95% CI=0.40-1.44). CONCLUSION: We
      found no clinical benefit of replacing a long-term catheter at the onset of the
      catheter-associated UTI. Further research is needed through randomized controlled
      trials.

PMID- 30094821
TI  - The role of prehabilitation in frail surgical patients: A systematic review.
AB  - INTRODUCTION: Increasing emphasis is being placed on the detection of frailty in
      the pre-operative setting given its association with surgical morbidity and
      mortality. Prehabilitation seeks to increase the physiological reserve of frail
      patients, attenuating the risk of irreversible functional decline following
      surgery. AIM/HYPOTHESIS: This systematic review appraises the evidence available
      for prehabilitation in frail surgical patients. We proposed that exercise
      prehabilitation would especially benefit frail patients, with improvements in pre
      operative functional capacity, and reductions in complications and length of
      hospital stay. METHODS: A literature search was conducted in MEDLINE, PubMed and
      CINAHL databases. Studies were included if they consisted of a prehabilitation
      intervention in frail patients undergoing surgery and specified a frailty
      model/index. Eight studies were included for analysis, 2 of which are ongoing
      studies. RESULTS: In 3 studies, prehabilitation consisted of an exercise
      intervention alone. There was a high feasibility of prehabilitation and a trend
      to improved pre-operative function, however, no evidence of improved post
      operative functional recovery was there. In 2 studies, prehabilitation consisted
      of both exercise and nutritional interventions. Reductions in mortality and
      duration of hospital stay were reported, but the quality of evidence was judged
      to be very low. There was a lack of evidence of improved outcomes following pre
      operative inspiratory muscle training in frail patients. DISCUSSION: This
      systematic review focuses on prehabilitation in frail surgical patients and
      reports that evidence supporting any outcome is limited, despite high feasibility
      and acceptability. There is a need for large randomised controlled trials to
      better establish the effects of prehabilitation in frail patients.

PMID- 30094822
TI  - Reply to: Use of Antiepileptic Drugs and Dementia Risk-an Analysis of Finnish
      Health Register and German Health Insurance Data.

PMID- 30094825
TI  - Safety Threshold Considerations for Sunscreen Systemic Exposure: A Simulation
      Study.
AB  - Sunscreens are regulated as over-the-counter drugs in the United States. Some
      sunscreen ingredients are absorbed into the systemic circulation, which raises
      concerns about the safety of these drugs. There is limited information on the
      systemic exposure for most sunscreen ingredients. This report estimates the
      systemic absorption of two sunscreen active ingredients, oxybenzone and
      enzacamene, by developing a pharmacokinetic model from published sunscreen
      absorption data and compares the results with safety thresholds proposed by the
      US Food and Drug Administration and in the literature. Our analysis indicates
      that systemic absorption can be substantial, and evaluation of the systemic
      exposure of sunscreen ingredients is warranted to better assess any long-term
      risks of use.

PMID- 30094826
TI  - Unusual hair findings in a child with cardiofaciocutaneous syndrome.

PMID- 30094827
TI  - Reply to: Association Between Proton Pump Inhibitors and Alzheimer's Disease in
      Older Adults.

PMID- 30094823
TI  - Long-Term Nursing Home Entry: A Prognostic Model for Older Adults with a Family
      or Unpaid Caregiver.
AB  - OBJECTIVES: To comprehensively examine factors associated with long-term nursing
      home (NH) entry from 6 domains of older adult and family caregiver risk from
      nationally representative surveys and develop a prognostic model and a simple
      scoring system for use in risk stratification. DESIGN: Retrospective
      observational study. SETTING: National Long-Term Care Surveys 1999 and 2004 and
      National Health and Aging Trends Study 2011 and linked caregiver surveys.
      PARTICIPANTS: Community-living older adults receiving help with self-care
      disability and their primary family or unpaid caregiver (N=2,676). MEASUREMENTS:
      Prediction of long-term NH entry (>100 days or ending in death) by 24 months
      follow up, ascertained from Minimum Data Set assessments and dates of death from
      Medicare enrollment files. Risk factors were measured from survey responses.
      RESULTS: In total, 16.1% of older adults entered a NH. Our final model and risk
      scoring system includes 7 independent risk factors: older adult age (1 point/5
      years), living alone (5 points), dementia (3 points), 3 or more of 6 self-care
      activities (2 points), caregiver age (45-64: 1 point, 65-74: 2 points, >=75: 4
      points), caregiver help with money management (2 points), and caregiver report of
      moderate (2 points) or high (4 points) strain. Using this model, participants
      were assigned to risk quintiles. Long-term NH entry was 7.0% in the lowest
      quintile (0-6 points), 20.4% in the middle 3 quintiles (7-14 points), and 30.9%
      in the highest quintile (15-22 points). The model was well calibrated and
      demonstrated moderate discrimination (c-statistic=0.670 in the original data, c
      statistic=0.647 in bootstrapped samples, c-statistic=0.652 using the point
      scoring system). CONCLUSION: We developed a prognostic model and simple scoring
      system that may be used to stratify risk of long-term NH entry of community
      living older adults. Our model may be useful for population health and policy
      applications.

PMID- 30094824
TI  - Burden of Depressive Symptoms Over 2 Decades and Risk of Nursing Home Placement
      in Older Women.
AB  - OBJECTIVES: To determine the association between cumulative burden of depressive
      symptoms and risk of nursing home (NH) placement over 2 decades. DESIGN:
      Prospective cohort study with data linked to Medicare claims files. SETTING:
      Clinic sites in Baltimore, Maryland; Minneapolis, Minnesota; and the Monongahela
      Valley near Pittsburgh, Pennsylvania. PARTICIPANTS: Initially community-dwelling
      women aged 65 and older (N=3,646). MEASUREMENTS: Depressive symptom burden was
      determined using the Geriatric Depression Scale measured over 18 years to
      calculate accumulation of burden. NH placement was determined using Medicare
      claims data. RESULTS: In Fine-Gray proportional hazards analyses including
      demographic characteristics, medical comorbidities, functional impairment, and
      recent depression exposure and accounting for competing risk of death, women with
      low depressive symptom burden were twice as likely to experience NH placement as
      those with minimal burden (hazard ratio (HR) = 1.92, 95% confidence interval (CI)
      = 1.16-3.20), women with moderate burden were more than twice as likely (HR =
      2.62, 95% CI = 1.59-4.31), and women with high burden (HR = 3.08, 95% CI = 1.87
      5.08) were three times as likely. The addition of antidepressant use to this
      model attenuated the risk only slightly. CONCLUSION: In older women, cumulative
      burden of depressive symptoms over nearly 2 decades is associated with greater
      risk of transitioning from community-living to a NH irrespective of recent
      depression exposure, medical comorbidities, functional impairment, and the
      competing risk of death. This work supports the need for improving recognition,
      monitoring, and treatment of depressive symptoms early, which may reduce or delay
      NH placement.

PMID- 30094828
TI  - Burden of Invasive Methicillin-Resistant Staphylococcus aureus Infections in
      Nursing Home Residents.
AB  - OBJECTIVES: To describe the epidemiology and incidence of invasive methicillin
      resistant Staphylococcus aureus (MRSA) infections in nursing home (NH) residents,
      which has previously not been well characterized. DESIGN: Retrospective analysis
      of public health surveillance data. SETTING: Healthcare facilities in 33 U.S.
      counties. PARTICIPANTS: Residents of the surveillance area. MEASUREMENTS: Counts
      of NH-onset and hospital-onset (HO) invasive MRSA infections (cultured from
      sterile body sites) identified from the Centers for Disease Control and
      Prevention Emerging Infections Program (EIP) population-based surveillance from
      2009 to 2013 were compared. Demographic characteristics and risk factors of NH
      onset cases were analyzed. Using NH resident-day denominators from the Centers
      for Medicare and Medicaid Services Skilled Nursing Facility Cost Reports,
      incidence of NH-onset invasive MRSA infections from facilities in the EIP area
      was determined. RESULTS: A total of 4,607 NH-onset and 4,344 HO invasive MRSA
      cases were reported. Of NH-onset cases, median age was 74, most infections were
      bloodstream infections, and known risk factors for infection were common: 1,455
      (32%) had previous MRSA infection or colonization, 1,014 (22%) had decubitus
      ulcers, 1,098 (24%) had recent central venous catheters, and 1,103 (24%) were
      undergoing chronic dialysis; 2,499 (54%) had been discharged from a hospital in
      the previous 100 days. The in-hospital case-fatality rate was 19%. The 2013
      pooled mean incidence of NH-onset invasive MRSA infections in the surveillance
      area was 2.4 per 100,000 patient-days. CONCLUSION: More NH-onset than HO cases
      occurred, primarily in individuals with known MRSA risk factors. These data
      reinforce the importance of infection prevention practices during wound and
      device care in NH residents, especially those with a history of MRSA infection or
      colonization.

PMID- 30094829
TI  - Comment on: Use of Antiepileptic Drugs and Dementia Risk.

PMID- 30094830
TI  - Higher Quality, Lower Cost with an Innovative Geriatrics Consultation Service.
AB  - OBJECTIVES: To design a value-driven, interprofessional inpatient geriatric
      consultation program coordinated with systems-level changes and studied outcomes
      and costs. DESIGN: Propensity-matched case-control study of older adults
      hospitalized at an academic medical center (AMC) who did or did not receive
      geriatric consultation. SETTING: Single tertiary-care AMC in Portland, Oregon.
      PARTICIPANTS: Adults aged 70 and older who received an inpatient geriatric
      consultation (n=464) and propensity-matched controls admitted before development
      of the consultation program (n=2,381). Pre- and postintervention controls were
      also incorporated into cost difference-in-difference analyses. MEASUREMENTS:
      Daily charges, total charges, length of stay (LOS), 30-day readmission, intensive
      care unit (ICU) days, Foley catheter days, total medication doses per day, high
      risk medication doses per day, advance directive and Physician Orders for Life
      Sustaining Treatment (POLST) documentation, restraint orders, discharge to home,
      and mortality. RESULTS: On average, individuals who received a geriatric
      consultation had $611 lower charges per day than those without a consultation
      (p=.02). They spent on average 0.36 fewer days in the ICU (p<.001). They were
      less likely to have restraint orders (20.0% vs 27.9%, p<0.001), more likely to
      have a POLST (58.2% vs 44.6%, p<.001), and more likely to be discharged to home
      (33.4% vs 28.2%, p=.03). They received fewer doses of antipsychotics,
      benzodiazepines, and antiemetics (10, 5, and 7 fewer doses per 100 patient-days,
      respectively) and had lower in-hospital mortality (2.4% vs 4%, p=.01). There was
      no difference in hospital LOS or 30-day readmission. CONCLUSION: Our consultation
      program resulted in significant reductions in daily charges, ICU days,
      potentially inappropriate medication use, and use of physical restraints and
      increased end-of-life planning. This model has potential for dissemination to
      other institutions operating in resource-scarce, value-driven settings.

PMID- 30094831
TI  - Association Between Proton Pump Inhibitor Use and Alzheimer's Disease in Older
      Adults.

PMID- 30094832
TI  - Secondary syphilis presented with impetigo-like lesions: a rare case report.

PMID- 30094833
TI  - Vanillin biotechnology: the perspectives and future.
AB  - The biotechnological production of fragrances is a recent trend that has expanded
      rapidly in the last two decades. Vanillin is the second most popular flavoring
      agent after saffron and is extensively used in various applications, e.g., as a
      food additive in food and beverages and as a masking agent in various
      pharmaceutical formulations. It is also considered a valuable product for other
      applications, such as metal plating and the production of other flavoring agents,
      herbicides, ripening agents, antifoaming agents, and personal and home-use
      products (such as in deodorants, air fresheners, and floor-polishing agents). In
      general, three types of vanillin, namely natural, biotechnological, and
      chemical/synthetic, are available on the market. However, only natural and nature
      identical (biotechnologically produced from ferulic acid only) vanillins are
      considered as food-grade additives by most food-safety control authorities
      worldwide. In the present review, we summarize recent trends in fermentation
      technology for vanillin production and discuss the importance of the choice of
      raw materials for the economically viable production of vanillin. We also
      describe the key enzymes used in the biotechnological production of vanillin as
      well as their underlying genes. Research to advance our understanding of the
      molecular regulation of different pathways involved in vanillin production from
      ferulic acid is still ongoing. The enhanced knowledge is expected to offer new
      opportunities for the application of metabolic engineering to optimize the
      production of nature-identical vanillin. (c) 2018 Society of Chemical Industry.

PMID- 30094834
TI  - Hemoglobin as an indicator of disease activity in severe hidradenitis
      suppurativa.

PMID- 30094835
TI  - The effect of range overlap on ecological niche divergence depends on spatial
      scale in monkeyflowers.
AB  - Patterns of niche divergence and geographical range overlap of closely related
      species provide insights into the evolutionary dynamics of ecological niches.
      When ranges overlap, shared selective pressures may preserve niche similarity
      along coarse-scale macrohabitat axes (e.g., bioclimates). Alternatively,
      competitive interactions may drive greater divergence along local-scale
      microhabitat axes (e.g., micro-topographical features). We tested these
      hypotheses in 16 species pairs of western North American monkeyflowers
      (Erythranthe and Diplacus, formerly Mimulus) with estimations of species' niches,
      geographic ranges, and a robust phylogeny. We found that macrohabitat niche
      divergence decreased with increasing range overlap, consistent with convergent
      selection operating at a coarse scale. No significant relationship was detected
      for microhabitat niches. Additionally, niche divergence was greater for recently
      diverged pairs along all macrohabitat niche axes, but greater for distantly
      diverged pairs along one microhabitat axis related to vegetation cover. For
      species pairs with partially overlapping ranges, greater microhabitat divergence
      was detected in sympatry than in allopatry for at least one niche axis for three
      of four pairs, consistent with character displacement in sympatry. Thus, coarse-
      and local-scale niche divergence show dissimilar patterns in relation to range
      overlap and divergence time, perhaps because the relative importance of
      convergent versus divergent selection depends on spatial scale.

PMID- 30094836
TI  - YAP and TAZ, the conductors that orchestrate eye development, homeostasis, and
      disease.
AB  - Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding
      motif (TAZ) are transcriptional coactivators established as a nexus in numerous
      signaling pathways, notably in Hippo signaling. Previous research revealed
      multifarious function of YAP and TAZ in oncology and cardiovasology. Recently,
      the focus has been laid on their pivotal role in eye morphogenesis and
      homeostasis. In this review, we synthesize advances of YAP and TAZ function
      during eye development in different model organisms, introduce their function in
      different ocular tissues and eye diseases, and highlight the potential for
      therapeutic interventions.

PMID- 30094838
TI  - Pemphigus vulgaris with vegetating feature confined to the scalp.

PMID- 30094837
TI  - Comparative Assessment of Utilization and Hospital Outcomes of Veterans Receiving
      VA and Non-VA Outpatient Dialysis.
AB  - OBJECTIVE: Growing demand for VA dialysis exceeds its supply and travel distances
      prohibit many Veterans from receiving dialysis in a VA facility, leading to
      increased use of dialysis from non-VA providers. This study compared utilization
      and hospitalization outcomes among Veterans receiving chronic dialysis in VA and
      non-VA settings in 2008-2013. DATA SOURCES: VA, Medicare, and national disease
      registry data. STUDY DESIGN: National cohort of 27,301 Veterans initiating
      dialysis, observed for a period of 2 years after treatment initiation. We used
      multinomial logistic regression to examine associations between patient
      characteristics and dialysis use in VA, non-VA community settings via VA
      Purchased Care (VA-PC), community settings via Medicare, or Dual settings. Zero
      inflated negative binomial regression was used to compare risk of hospitalization
      and days spent in the hospital across dialysis settings. PRINCIPAL FINDINGS:
      Sixty-seven percent of Veterans obtained community-based dialysis exclusively via
      Medicare, 11 percent in the community via VA-PC, 4 percent in VA, and 18 percent
      in Dual settings. Financial and geographic access factors were important
      predictors of dialysis setting, but days spent in the hospital and risk of
      hospitalization did not differ meaningfully across settings. CONCLUSIONS: Most
      Veterans obtained dialysis in the community. Dialysis setting appeared to have
      little impact on risk of hospitalization among Veterans.

PMID- 30094839
TI  - Blends of lemongrass derivatives and lime for the preparation of mixed beverages:
      antioxidant, physicochemical, and sensory properties.
AB  - BACKGROUND: Lemongrass is an aromatic plant with antioxidant and antimicrobial
      properties, used for the preparation of medicinal tea and for essential oil
      production. Previous studies have shown that extracts of lemongrass leaves
      contain phenolic compounds associated with health benefits. Although essential
      oils have been widely used as flavoring agents, there is no scientific evidence
      regarding the use of lemongrass essential oils in beverages. Thus, the objectives
      of the present study were to develop blends with lemongrass derivatives (aqueous
      extract, lyophilized extract, and essential oil) and lime juice for the
      preparation of mixed beverages, to evaluate the antioxidant and physicochemical
      characteristics of blends, and to determine the sensory profile and acceptance of
      mixed beverages. RESULTS: The formulated blends showed favorable physicochemical
      characteristics such as acidity and color, and they contained bioactive compounds
      (phenolics and vitamin C) and important antioxidant properties. Mixed beverages
      prepared from blends containing aqueous extract or lyophilized extract plus
      essential oil, which showed higher intensity of lemongrass aroma and flavor, were
      more readily accepted. CONCLUSION: This study demonstrates that it is possible to
      make suitable blends with lemongrass derivatives and lime juice for the
      preparation of high-quality mixed beverages with sensory pleasantness, and
      potentially beneficial health components. (c) 2018 Society of Chemical Industry.

PMID- 30094840
TI  - Phytochemical profile, nutraceutical potential and functional properties of
      Cucumis melo L. seeds.
AB  - BACKGROUND: This study investigated the amino acids, phenolic compounds and
      volatile compounds in Maazoun melon seeds. The functional properties of melon
      seed flour, such as bulk density, swelling capacity, emulsifying capacity, and
      foaming capacity were also determined. RESULTS: The findings proved that the
      functional properties of melon seeds make them useful for incorporation into
      different food formulations to improve their functionality. The determination of
      the amino acid composition of melon seeds showed that glutamic acid (205.23 g kg
      1 ), arginine (130.44 g kg-1 ), and tryptophan (129.91 g kg-1 ) were the major
      amino acids of the protein fraction. Chromatographic analysis indicated that
      phenolic acids (47.78%) constituted the main phenolic class, followed by
      flavonoids (27.15%). Naringenin-7-O-glycoside and gallic acid were the most
      abundant phenolic compounds. Gas chromatography (GC) and gas chromatography-mass
      spectrometry (GC-MS) analyses of the volatile compounds demonstrated that esters
      and terpenoids were the main volatile groups. The study of histological
      structures showed that melon seeds consist of three distinguishable parts:
      tegument, endosperm cells, and almond. CONCLUSION: The results obtained revealed
      that melon (Cucumis melo L.) seeds may be a potential source of bioactive
      compounds and natural substances with nutritive value and functional properties
      of interest to industrial applications. (c) 2018 Society of Chemical Industry.

PMID- 30094841
TI  - Incidental diagnosis of blastic plasmacytoid dendritic cell neoplasm in skin
      excision for basal cell carcinoma.

PMID- 30094842
TI  - The Importance of Venous Return in Starling-Like Control of Rotary Ventricular
      Assist Devices.
AB  - Rotary ventricular assist devices (VADs) are less sensitive to preload than the
      healthy heart, resulting in inadequate flow regulation in response to changes in
      patient cardiac demand. Starling-like physiological controllers (SLCs) have been
      developed to automatically regulate VAD flow based on ventricular preload. An SLC
      consists of a cardiac response curve (CRC) which imposes a nonlinear relationship
      between VAD flow and ventricular preload, and a venous return line (VRL) which
      determines the return path of the controller. This study investigates the
      importance of a physiological VRL in SLC of dual rotary blood pumps for
      biventricular support. Two experiments were conducted on a physical mock
      circulation loop (MCL); the first compared an SLC with an angled physiological
      VRL (SLC-P) against an SLC with a vertical VRL (SLC-V). The second experiment
      quantified the benefit of a dynamic VRL, represented by a series of specific
      VRLs, which could adapt to different circulatory states including changes in
      pulmonary (PVR) and systemic (SVR) vascular resistance versus a fixed
      physiological VRL which was calculated at rest. In both sets of experiments, the
      transient controller responses were evaluated through reductions in preload
      caused by the removal of fluid from the MCL. The SLC-P produced no overshoot or
      oscillations following step changes in preload, whereas SLC-V produced 0.4 L/min
      (12.5%) overshoot for both left and right VADs. Additionally, the SLC-V had
      increased settling time and reduced controller stability as evidenced by
      transient controller oscillations. The transient results comparing the specific
      and standard VRLs demonstrated that specific VRL rise times were improved by
      between 1.2 and 4.7 s ( x- = 3.05 s), while specific VRL settling times were
      improved by between 2.8 and 16.1 seconds ( x- = 8.38 s) over the standard VRL.
      This suggests only a minor improvement in controller response time from a dynamic
      VRL compared to the fixed VRL. These results indicate that the use of a fixed
      physiologically representative VRL is adequate over a wide variety of
      physiological conditions.

PMID- 30094844
TI  - Micronutrient productivity: a comprehensive parameter for biofortification in
      rice (Oryza sativa L.) grain.
AB  - BACKGROUND: Enhancing the micronutrient content of staple crops such as rice will
      improve human nutrition and address the problem of hidden hunger globally. Rice
      grains consumed after polishing lack adequate amounts of micronutrients. The
      present study aims to reveal the effects of polishing on micronutrient content
      and to identify superior genotype(s) to improve yield and micronutrient content
      after polishing. RESULTS: AM65 exhibited the highest zinc content, and AM180 had
      the highest iron content, even after polishing. There was little or no difference
      between the genotypes for zinc content in bran, indicating a possible threshold
      for micronutrient accumulation in the aleurone layer. A comprehensive selection
      criterion called 'micronutrient productivity' was used to select for both yield
      and micronutrient parameters. AM65 and ARB6 showed high zinc and iron
      productivity indices. OsZIP4b and OsZIP6c markers showed an association with iron
      content on an agarose gel. Sequencing of markers revealed that OsYSL15 and
      OsZIP6c were associated with grain zinc content and OsZIP3b, OsMTP1a, and OsYSL4b
      with grain iron content. These markers can be used for selecting superior
      accessions. CONCLUSION: AM65 was loaded with micronutrients and manifested a
      positive correlation with the grain yield, and it is undoubtedly 'super elite'.
      Bran does not drain the grain but rather acts as gateway for micronutrient
      transportation to the endosperm. Micronutrient productivity is a comprehensive
      parameter for the biofortification of grain. (c) 2018 Society of Chemical
      Industry.

PMID- 30094845
TI  - Impact of steam treatment on shelf-life stability of a xanthone-rich green herbal
      tea (Cyclopia maculata Andrews Kies) - identifying quality changes during
      storage.
AB  - BACKGROUND: Steam treatment of shredded, fresh C. maculata (honeybush) plant
      material improves the aroma of this green herbal tea with a slight impact on
      color and phenolic content, but the effect on storage stability is not known.
      RESULTS: Steam-treated (60 s before drying) and untreated (control) dried plant
      material was stored under normal storage conditions in semi-permeable sachets at
      25  degrees C and 60% relative humidity. Reference samples of treated (steamed)
      and untreated (control) material were stored at 0  degrees C in impermeable
      pouches for maximum retention of quality. The stability of the herbal tea was
      assessed in terms of sensory profile, phenolic composition and color over a
      storage period of 6 months. Normal storage conditions resulted in a significant
      (P < 0.05) decrease in green color, especially in steamed samples. Intensities of
      fruity and sweet-associated aroma attributes increased progressively during
      storage, while the opposite was observed for vegetal and cereal-like attributes.
      These changes in the aroma profile were more pronounced in untreated (control)
      samples. Individual phenolic content remained stable during storage. CONCLUSIONS:
      Storage of 3 to 6 months may result in a more appealing aroma profile and
      enhanced product quality, despite loss of green color. (c) 2018 Society of
      Chemical Industry.

PMID- 30094843
TI  - Maternal plasma metabolic fingerprint indicative for fetal Down syndrome.
AB  - OBJECTIVE: The objective of the study was to perform maternal plasma metabolic
      fingerprinting to evaluate differences in plasma metabolites between healthy and
      Down syndrome (DS) pregnancies and to indicate novel non-invasive markers for DS
      prenatal diagnostics. METHODS: This was a case-control study of pregnancies
      between 15th and 18th gestational week. LC-MS-based metabolic fingerprinting of
      plasma samples was performed. RESULTS: Levels of five metabolites were
      significantly lower in the plasma of DS pregnancies. The majority of the
      statistically significant metabolites may be connected with fetal brain and
      central nervous system development (eg, fatty acid amides). According to the
      receiver operating characteristic (ROC), the combination of linoleamide and
      piperine has the highest diagnostic potential: area under the curve (AUC) =
      0.878, sensitivity of 100%, and specificity of 73.3%. CONCLUSIONS: The study
      indicates disturbances in maternal metabolic pathways evoked by fetal DS. Novel
      potential maternal plasma metabolomic markers for non-invasive prenatal
      diagnostics of fetal DS are proposed.

PMID- 30094847
TI  - Results and complications after removal of tibial tuberosity advancement cage for
      treatment of surgical site infections: A retrospective study.
AB  - OBJECTIVE: To describe the surgical technique and report the short-term results
      after removal of tibial tuberosity advancement (TTA) cages in dogs with surgical
      site infections (SSI). STUDY DESIGN: Retrospective clinical study. ANIMALS:
      Seventeen client-owned dogs. METHODS: Medical records of dogs treated for SSI by
      removal of a TTA cage between November 2012 and May 2015 were reviewed.
      Information collected included signalment, physical examination findings,
      affected stifle, cage size, date of SSI onset, time elapsed to implant removal,
      duration of procedure, culture results, any complications encountered, timing of
      follow-up recheck, and short-term results. RESULTS: Seventeen dogs (20 stifles)
      were included. Clinical signs related to SSI started at a mean of 403 days after
      TTA, and implants were removed 474 days (mean) after TTA. No intraoperative
      complications were reported. Postoperative complications occurred in 40% of dogs.
      Three dogs developed major complications, including a tibial tuberosity fracture.
      Eighty-five percent of owners reported complete resolution of clinical signs
      related to the SSI and were satisfied with the outcome. CONCLUSION: Surgical site
      infections were short- and long-term complications successfully treated by
      removal of the TTA cage in the majority of dogs in this study, although
      complications were common. CLINICAL SIGNIFICANCE: Removal of the TTA cage can be
      considered as an adjunct to treat SSI but has the potential for postoperative
      complications.

PMID- 30094846
TI  - Depressive symptoms and error-related brain activity in CPS-referred children.
AB  - Early adversity such as maltreatment is associated with increased risk for
      psychopathology and atypical neurological development in children. The present
      study examined associations between depressive symptoms and error-related brain
      activity (the error-related negativity, or ERN) among children involved with
      Child Protective Services (CPS) and among comparison children. Results indicate
      that the relation between depressive symptoms and ERN amplitude depends on CPS
      involvement, such that depressive symptoms were associated with blunted ERNs only
      for CPS-referred children. The present study can inform future research
      investigating the mechanisms by which experiences of adversity affect the
      association between symptoms and error-related brain activity.

PMID- 30094848
TI  - Leaf removal at veraison stage differentially affects qualitative attributes and
      bioactive composition of fresh and dehydrated grapes of two indigenous Cypriot
      cultivars.
AB  - BACKGROUND: The effect of leaf removal on postharvest performance of dehydrated
      grapes has been poorly analyzed. The aim of this study was to evaluate the effect
      of leaf removal at veraison stage on the metabolites of fresh and dehydrated
      grapes of two indigenous Cypriot cultivars ('Mavro' and 'Xynisteri'), which are
      destined for the production of 'Commandaria', a protected designation of origin
      (PDO) premium sweet wine. RESULTS: Leaf removal led to a reduction of soluble
      solids, titratable acidity, aroma potential and most of the phenolic groups in
      the musts of both cultivars. Dehydration led to a significant increase in all of
      these parameters in both cultivars, being more pronounced in cv. 'Mavro'.
      Interestingly, leaf removal indicated differential response in the dehydrated
      product of the cultivars examined; liquid chromatography (LC-DAD-qTOF-MS) data
      showed a significant decrease in phenolic compounds in 'Xynisteri' must (from
      66.73 to 44.15 mg L-1 ), while 'Mavro' must registered similar values of phenolic
      compounds (from 94.78 to 96.72 mg L-1 ), but with a different distribution among
      phenolic groups. Intriguingly, flavonols and flavan-3-ols that present
      significant health-promoting properties showed higher concentrations in the must
      from dehydrated 'Mavro' grapes that were subjected to preharvest leaf removal.
      CONCLUSIONS: Leaf removal at veraison stage followed by sun drying differentially
      affected the chemical composition of the examined cultivars. This preharvest
      application followed by postharvest dehydration was beneficial for cv. 'Mavro',
      while this was not the case for cv. 'Xynisteri'. The effects of leaf removal in
      other developmental stages (i.e. pre/post bloom stage) need to be dissected with
      the ultimate goal of providing an end product with high bioactive content. (c)
      2018 Society of Chemical Industry.

PMID- 30094849
TI  - Evaluation of the effects of initial water temperature and curing time on
      fiberglass cast strength.
AB  - OBJECTIVE: To determine the effects of water temperature and cure time on cast
      strength. STUDY DESIGN: Prospective randomized experimental study. METHODS: Two
      water temperatures were tested, 23 degrees C (cold) and 42 degrees C (warm). Cast
      constructs were made of 4-inch fiberglass casting material over a rubber mandrel.
      Each construct was divided into 3 segments and tested in 4-point bending at 0.5,
      1, and 24 hours. Stiffness and bending moment, cumulative energy, and angular
      deformation at yield and failure were recorded and analyzed by using repeated
      measures ANOVA. RESULTS: Mean time +/- SD to complete the construct was 2.2 +/-
      0.8 and 2.3 +/- 0.6 minutes for warm and cold water, respectively. Warm water and
      longer cure times produced constructs with greater stiffness (23.05 vs 20.88
      newton-meter degrees [Nm degrees ] at 0.5 hours), bending moment (121.75 vs
      107.31 Nm degrees  at 0.5 hours), and cumulative energy (557.33 vs 428.89 Nm
      degrees  at 1 hour) at yield and failure. Longer cure time significantly
      increased angular deformation of rods at failure; however, water temperature did
      not. In general, the strongest casts were produced with warm water and after
      curing for 24 hours. CONCLUSION: Fiberglass casts continued to gain strength for
      at least 24 hours. Use of warm water increased the rate of curing, resulting in
      stronger constructs at earlier time points. CLINICAL SIGNIFICANCE: Use of warm
      water is recommended to initiate fiberglass cast curing, especially if the casted
      limb will be loaded soon after cast application.

PMID- 30094850
TI  - Gluten-free sorghum pasta: starch digestibility and antioxidant capacity compared
      with commercial products.
AB  - BACKGROUND: The development of new products with a focus on nutrition, rather
      than other technical aspects, is essential to improve the quality of celiac
      diets. Nutritional attributes of white and brown sorghum gluten-free pasta
      developed in a previous work were analyzed. The extent and kinetics of starch in
      vitro digestion, estimated glycemic index (eGI), potentially bioaccessible and
      dialyzable polyphenols, and antioxidant activity were evaluated and compared with
      commercial products. RESULTS: Sorghum flour samples were used to obtain pasta
      with high protein (~170 g kg-1 ), dietary fiber (~80 g kg-1 ), polyphenols (2.6 g
      GA kg-1 pasta), and antioxidant activity. This sorghum pasta showed slower starch
      in vitro digestion than the other gluten-free pasta, with a high level of protein
      hydrolysis (76%). The highest eGI was observed in a rice sample (69.8) followed
      by a corn-based pasta (66.4). White and brown sorghum gluten-free pasta showed
      2.9 and 2.4 times, respectively, higher potentially bioaccessible polyphenol
      content compared to that in cooked pasta. No significant variation in antioxidant
      activity was found in sorghum pasta after digestion and around 48% and 36% of
      activity was detected in dialysate. CONCLUSION: Both types of sorghum gluten-free
      pasta have demonstrated their nutritional value and represent a good potential
      alternative to current commercial pasta. (c) 2018 Society of Chemical Industry.

PMID- 30094851
TI  - Thorough characterization and stability of HP-beta-cyclodextrin thymol inclusion
      complexes prepared by microwave technology: A required approach to a successful
      application in food industry.
AB  - BACKGROUND: The aims of the present study were to obtain a stable dry powder
      formulation of cyclodextrins (CDs) encapsulating thymol, for successful use as an
      ingredient on an industrial scale, and to characterize the thymol-CDs complexes
      using different techniques. RESULTS: Thymol was successfully solubilized in
      aqueous solutions and the Kc value increased with the pH of the media until the
      pH was neutral, giving the highest values (2583 +/- 176 L mol-1 ) for HP-beta
      cyclodextrins (HP-beta-CDs). The best encapsulation efficiency of thymol in solid
      complexes was obtained using the microwave (MWI) encapsulation method. The
      different characterization techniques have demonstrated the affinity of HP-beta
      CDs for thymol molecules, forming stable complexes. CONCLUSIONS: The results
      support the use of the MWI method in the preparation of solid HP-beta-CD-thymol
      complexes, due to greater encapsulation efficiency and technological and economic
      advantages for industrial applications. (c) 2018 Society of Chemical Industry.

PMID- 30094852
TI  - Effects of dietary zinc oxide nanoparticles supplementation on growth
      performance, zinc status, intestinal morphology, microflora population, and
      immune response in weaned pigs.
AB  - BACKGROUND: This study evaluated the effects of dietary zinc oxide nanoparticles
      (nano-ZnOs) on growth performance, zinc status, intestinal morphology, microflora
      population, and immune response in weaned piglets. A total of 150 weaned piglets
      (9.37 +/- 0.48 kg) were randomly allotted to five dietary treatments and fed with
      a basal diet (control), or the basal diet supplemented with nano-ZnOs at 150,
      300, or 450 mg kg-1 , and 3000 mg kg-1 ZnO for 21 days. After a feeding test, six
      pigs from the control, 450 mg kg-1 nano-ZnOs and 3000 mg kg-1 ZnO groups were
      slaughtered. RESULTS: Compared with the control, dietary supplements of nano-ZnOs
      and ZnO could improve (P < 0.05) average daily weight gain (ADG), average daily
      feed intake (ADFI), and villus height to crypt depth ratio in the duodenum and
      jejunum, and decrease (P < 0.05) diarrhea incidence. Zinc retention in the serum,
      heart, liver, spleen and kidney of pigs supplemented with nano-ZnOs and ZnO was
      increased (P < 0.05). Nano-ZnOs decreased (P < 0.05) the zinc excretion compared
      with conventional ZnO. Lower Escherichia coli counts in the cecum, colon, and
      rectum were observed (P < 0.05) in the nano-ZnOs group compared with the other
      groups. Compared with the control, ZnO and nano-ZnOs increased (P < 0.05) the
      serum concentration of IgA, IL-6, and TNF-alpha, and decreased (P < 0.05) the
      concentration of IgM. CONCLUSION: These results indicated that low doses of nano
      ZnOs can have beneficial effects on growth performance, intestinal morphology and
      microflora, and immunity in weanling pigs, which are similar to the effects of
      pharmacological dosages of conventional ZnO. Nano-ZnOs may reduce mineral
      excretion, which may reduce environmental challenges. (c) 2018 Society of
      Chemical Industry.

PMID- 30094853
TI  - Chromosomal microarray analysis on uncultured chorionic villus sampling can be
      complicated by confined placental mosaicism for aneuploidy and microdeletions.
AB  - OBJECTIVE: This study aims to establish the incidence and implications of
      confined placental mosaicism (CPM) in the context of prenatal chromosomal
      microarray analysis (CMA). METHODS: We retrospectively reviewed prenatal array
      data on 1382 consecutive chorionic villus sampling (CVS) specimens spanning the
      past 6 years, focusing on those for which whole CVS biopsy (both cytotrophoblast
      and mesenchymal cells) was used for CMA and cultured cells (primarily mesenchyme)
      was also analyzed or amniotic fluid (AF)/newborn blood was used for confirmation,
      to determine the frequency of mosaic abnormal findings that were the result of
      CPM. RESULTS: Out of a total of 1382 consecutive CVS cases, we identified 42
      (42/1382 = 3.0%) cases with abnormal array findings suggestive of mosaicism.
      Among them, 10 cases were unequivocally interpreted as CPM based on a normal
      AF/newborn blood confirmatory result. In addition, another 10 cases were
      interpreted as provisional CPM based on normal results on cultured cells.
      Notably, 40% (8/20) of the cases revealed complex findings, including multiple
      mosaic aneuploidies, mosaic submicroscopic copy number variation (CNV), and
      mosaic aneuploidy plus mosaic CNV. CONCLUSION: Abnormal CMA results from CVS
      specimens should be interpreted with caution when mosaicism is evident or
      suspected. Furthermore, confirmatory testing on amniotic fluid, which contains
      cells derived from the fetus, is recommended in these cases.

PMID- 30094855
TI  - Aneurysmal fibrous histiocytomas with recurrent rearrangement of the PRKCD gene
      and LAMTOR1-PRKCD fusions.

PMID- 30094854
TI  - Decreased rectal meconium signal on MRI in fetuses with open spinal dysraphism.
AB  - OBJECTIVE: To evaluate rectal meconium signal in fetuses with open spinal
      dysraphism and correlate findings with postnatal exam. METHODS: This is a single
      institution Institutional Review Board-approved Health Insurance Portability and
      Accountability Act (HIPAA) compliant retrospective analysis of fetal MRIs of open
      spinal dysraphism from 2004 to 2016. Fetuses with diagnostic T1-weighted images
      and postnatal follow-up at our institution were included. RESULTS: A total of 115
      fetuses (average gestational age 23.9 +/- 3.6 weeks) met inclusion criteria. Of
      these, 80% (92/115) had T1 hyperintense rectal meconium signal. Average height of
      the meconium column, measured from the base of the bladder to its most inferior
      extent, was 9.2 +/- 4.3 mm in fetuses >=20-week gestational age and 11.1 +/- 4.4
      mm in fetuses >=23-week gestational age (n = 110) . None had bowel dilation. One
      of 115 fetuses had a simple form of anorectal malformation allowing complete
      repair in the neonatal period, but this fetus had a normal meconium column height
      on fetal MRI of 22 mm. The remaining 23/115 fetuses with lack of normal rectal
      meconium signal were born without evidence of anorectal malformation. CONCLUSION:
      Decreased or absent T1-hyperintense rectal meconium signal in fetuses with open
      spinal dysraphism does not correlate with imperforate anus postnatal and may be a
      reflection of neurogenic bowel in this patient population.

PMID- 30094856
TI  - Reducing saccadic artifacts and confounds in brain imaging studies through
      experimental design.
AB  - Saccades constitute a major source of artifacts and confounds in brain imaging
      studies. Whereas some artifacts can be removed by omitting segments of data,
      saccadic artifacts cannot be typically eliminated by this method because of their
      high occurrence rate even during fixation (1-3 per second). Some saccadic
      artifacts can be alleviated by offline-correction algorithms, but these methods
      leave nonnegligible residuals and cannot mitigate the saccade-related visual
      activity. Here, we propose a novel yet simple approach for diminishing saccadic
      artifacts and confounds through experimental design. We suggest that specific
      tasks can lead to substantially less saccade occurrences around the time of
      stimulus presentation, starting from slightly before its onset and lasting for a
      few hundred milliseconds. In three experiments, we compared the frequency and
      size of saccades in a variety of tasks. Results of Experiment 1 showed that a
      foveal change-detection task reduced the number and sizes of saccades, relative
      to a parafoveal orientation-discrimination task. Experiment 2 replicated this
      finding with a parafoveal object recognition task. Experiment 3 showed that both
      foveal and parafoveal continuous change detection tasks induced fewer and smaller
      saccades than a discrete orientation-discrimination task. We conclude that adding
      a foveal or a parafoveal continuous task reduces saccades' number and size. This
      would lead to better artifact correction and enable the omission of contaminated
      data segments. This study may be the first step toward developing saccade-free
      experimental designs.

PMID- 30094857
TI  - Older (but not younger) preschoolers reject incorrect knowledge claims.
AB  - As epistemic and normative learners, children are dependent on their developing
      skills for evaluating others' claims. This competence seems particularly
      important in the current digital age in which children need to discern valid from
      invalid assertions about the world in both real-life and virtual interactions to
      ultimately gather and accumulate robust knowledge. We investigated whether
      younger and older preschoolers (N = 48) understand that a speaker's knowledge
      claim ('I know where X is') may be correct or incorrect given objectively
      accessible information (about whether the speaker had perceptual access to a
      critical event). We found that both younger and older preschoolers accepted
      correct knowledge claims that matched observable reality, but that only older
      preschoolers reliably rejected incorrect knowledge claims that did not match
      reality (the speaker lacked perceptual access). Nevertheless, a considerable
      proportion of younger preschoolers both rejected incorrect knowledge claims and
      gave valid explanations, suggesting that the ability to scrutinize epistemic
      claims develops gradually from around 3 to 4 years of age. These findings may
      help integrate research on children's norm and theory of mind development.
      Statement of contribution What is already known on this subject? Preschoolers
      understand that non-epistemic claims (e.g., 'This is an X!') may be correct or
      incorrect, and they track a speaker's relevant characteristics in testimonial
      situations. It is not known what preschoolers understand about the validity of
      epistemic (knowledge) claims (e.g., 'I know that X'). What does this study add?
      Younger and older preschoolers accepted correct knowledge claims (children
      observed that a speaker saw a critical event and was thus knowledgeable). Only
      older preschoolers reliably rejected incorrect knowledge claims (the speaker did
      not see the critical event). Nevertheless, a considerable proportion of younger
      preschoolers showed competence in their evaluation of, and reasoning about,
      incorrect knowledge claims. Findings suggest that the ability to evaluate
      epistemic claims develops gradually from around 3 to 4 years of age.

PMID- 30094858
TI  - Effect of selective versus nonselective cyclooxygenase inhibitors on gastric
      ulceration scores and intestinal inflammation in horses.
AB  - OBJECTIVE: To determine whether a cyclooxygenase (COX)-2 selective nonsteroidal
      anti-inflammatory drug (NSAID) would reduce gastric ulceration and
      gastrointestinal (GI) inflammation compared with a non-COX selective NSAID. STUDY
      DESIGN: Randomized block design. ANIMALS: Twenty-five healthy adult horses.
      METHODS: Horses were randomly assigned to receive placebo (n = 5), phenylbutazone
      (n = 10), or firocoxib (n = 10) administered daily for 10 days. Gastroscopy was
      performed on days 0 and 10, and both squamous and glandular ulcers were scored
      according to established scoring criteria. Fecal samples were collected on days
      0, 10, and 20 to test for fecal myeloperoxidase (MPO) concentration by enzyme
      linked immunosorbent assay. RESULTS: Both classes of NSAID induced GI injury as
      determined by gastric ulceration scores and fecal MPO. Glandular gastric
      ulceration scores and fecal MPO concentrations were higher in horses treated with
      phenylbutazone at day 10 (P < .001 and P = .0018, respectively). Increases in
      fecal MPO were significantly decreased 10 days following cessation of treatment
      for firocoxib but remained greater than baseline for the phenylbutazone group.
      CONCLUSION: Although both classes of NSAID induced gastric ulceration, the COX-2
      selective NSAID firocoxib induced less severe glandular ulceration. Although
      there were increases in fecal MPO in both groups after 10 days of treatment, this
      increase was significant only in horses receiving the nonselective COX inhibitor
      phenylbutazone. CLINICAL SIGNIFICANCE: These findings suggest that both classes
      of NSAID induce GI injury in horses; however, at the dosages used in this study,
      the COX-2 selective NSAID firocoxib resulted in less severe injury.

PMID- 30094859
TI  - Post-veraison trimming slow down sugar accumulation without modifying phenolic
      ripening in Sangiovese vines.
AB  - BACKGROUND: Vineyard strategies have recently been developed to combat the
      effects of global warming on grapevines, which is causing grapes to ripen
      quickly, excessive sugar accumulation in berries, and high alcohol levels in
      wines. We evaluate the effectiveness of post-veraison trimming as a means of
      slowing down sugar accumulation, without modifying phenolic ripening, in
      Sangiovese vines grown in highly fertile and well watered soil. RESULTS: The
      removal of about two-thirds of the leaf area by shoot trimming after veraison led
      to a reduction in sugar content without affecting yield. Total and extractable
      anthocyanins, skin, and seed tannins showed no significant variation at harvest
      after the treatment during the three-year trial, while the replenishment of
      carbohydrates in canes at the end of the trial was negatively affected.
      CONCLUSIONS: These results indicate that, in highly fertile and well-watered
      soil, post-veraison trimming may represent a powerful tool for decreasing sugar
      concentration during harvest without affecting yield or total and extractable
      phenolic compounds. However, the reduction in starch reserves compared to the
      control serves as a warning about repeated trimming over the years. (c) 2018
      Society of Chemical Industry.

PMID- 30094860
TI  - Ventral stabilization of thoracic kyphosis through bilateral intercostal
      thoracotomies using SOP (String of Pearls) plates contoured after a 3-dimensional
      print of the spine.
AB  - OBJECTIVE: To describe a novel vertebral body stabilization and report its
      outcome in dogs with thoracic kyphosis and secondary myelopathy. STUDY DESIGN:
      Case series. ANIMALS: Six pugs with thoracic kyphosis and secondary myelopathy.
      METHODS: Medical records (2012-2017) of dogs with chronic progressive pelvic limb
      ataxia and ambulatory proprioceptive paraparesis due to thoracic kyphosis were
      reviewed. Dogs were evaluated via MRI and computed tomography. A 3-dimensional
      print of the kyphotic vertebral segment was used to precontour the SOP (String of
      Pearls) plates. Bilateral double, dorsal intercostal thoracotomies were performed
      to place precontoured SOP on the vertebral bodies. Long-term (6-16 months)
      clinical outcome was determined on the basis of neurological scoring (NS) and
      owner questionnaire. RESULTS: The only intraoperative complication consisted of a
      lung laceration due to preexisting adhesions. Postoperative complications
      included seroma formation (n = 2) and incidental radiographic evidence of screw
      breakage (n = 2). NS at presentation ranged between 2 and 4 and improved to 1 at
      long-term follow-up in all dogs but 1 (NS = 2). All owners felt that their dog
      had excellent quality of life at follow-up. CONCLUSION: In spite of the
      challenging local anatomy, all dogs undergoing vertebral stabilization with SOP
      placement experienced a good clinical outcome. CLINICAL SIGNIFICANCE:
      Stabilization of vertebral bodies with precontoured SOP placed through bilateral
      thoracotomies may be considered as a treatment option for dogs with thoracic
      kyphosis and secondary myelopathy.

PMID- 30094861
TI  - Contact allergy in Danish children: Current trends.
AB  - BACKGROUND: Contact allergy is common in children, but may be underdiagnosed.
      Importantly, the clinical relevance of specific allergies is subject to constant
      change, and it is therefore important to continuously monitor the trends and
      changes of contact allergies in the paediatric population. OBJECTIVES: To
      identify possible changes in contact allergy and allergic contact dermatitis
      among Danish children referred for patch testing. METHODS: A retrospective study
      was performed based on patch test data from the Danish National Database of
      Contact allergy. The current data were compared with previously published data on
      Danish children referred for patch testing. RESULTS: Between 2012 and 2016, 1573
      children and adolescents were patch tested. Overall, 385 (24.5%) had at least 1
      positive patch test reaction. The overall prevalence was similar in boys and
      girls, across age groups, and in patients with and without atopic dermatitis.
      Statistically significant increases in contact allergy to fragrances and
      isothiazoliones were seen, whereas a decrease in nickel allergy was found.
      CONCLUSION: Allergic contact dermatitis continues to be a common disease in
      children, and is even significantly increasing for some allergens.

PMID- 30094863
TI  - Allergic contact dermatitis secondary to the use of a bandage impregnated with
      benzalkonium chloride.

PMID- 30094862
TI  - The Challenging Pathway Toward Heart Transplant Listing for Adult Congenital
      Heart Disease Patients.
AB  - Adult congenital heart disease (ACHD) patients are at risk for end-stage heart
      failure; heart transplantation (Htx) represents the only definitive therapy
      available although not easily achievable for all patients. The study aims to
      assess the pathway difficulties and outcomes of ACHD patients with end-stage
      heart failure referred for Htx evaluation. This is a single center retrospective
      study on ACHD patients with end-stage heart failure referred to Htx evaluation
      from 2004 to 2015. Demographic data, medical history, failure modality, and
      follow-up were obtained from patient charts. End-points were Htx list enrollment,
      transplant, and survival. Statistical analysis was performed comparing patients
      listed and not listed. There were 21 ACHD patients with end-stage heart failure
      referred to Htx evaluation. Transplant listing was declined for 12 (57%)
      meanwhile 9 patients were listed. Htx was successfully achieved in 3 patients
      after 24 and 36 months, respectively. Three patients are still on the wait list
      and three died while waiting, with a listed group mortality of 33.3% (3/9).
      Mortality occurred in first 18 months after Htx list enrollment. Not listed group
      mortality was 50% (6/12) and occurred after a median time of 17.5 months (IQR: 9
      23 months). There was no difference in survival (P = 0.574) between listed and
      not listed (89, 63, and 63% vs. 83, 56, and 47% at 12-24-48 months). Follow-up
      median duration was 27 months (IQR: 14-56 months). Heart transplant listing for
      ACHD patients with end-stage heart failure is hard to obtain. Almost 2/3 of the
      patients were declined. Survival for these patients is reduced severely either in
      waiting list for transplant or excluded indicating the potential need of
      mechanical circulatory support as bridge to transplant or as destination therapy
      to improve survival likelihood.

PMID- 30094865
TI  - Association of Interleukin-1 beta and tumor necrosis factor-alpha genetic
      polymorphisms with gastric cancer in India.
AB  - Interleukin 1 beta (IL-1beta) and Tumor necrosis factor alpha (TNF-alpha) are key
      inflammatory cytokines whose polymorphisms have been correlated with increased
      susceptibility to gastric cancer (GC). Since geographical and racial differences
      exist in cancer rates, our study was aimed to evaluate the first possible
      association of polymorphisms in these genes with GC risk in West Bengal, India.
      Polymorphisms in IL-1beta and TNF-alpha genes were genotyped in 120 GC patients
      and 135 healthy individuals. Combined effect of the SNPs in both genes with GC
      risk was determined through allele dosage analysis (ADA) and the survival data
      were analyzed by Log Rank Test. The study results revealed that IL-1beta
      rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30-2.63) and
      rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67-3.83) and TNF-alpha
      rs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54-3.46)
      polymorphisms significantly contributed toward GC risk. Moreover, ADA showed that
      carriage of 7 "effective" risk alleles conferred a risk of almost 10-fold in
      comparison to individuals carrying less than 3 "effective" risk alleles. Our
      survival analysis also indicated a significant association between IL-1beta
      rs1143627: T > C and rs16944: C > T and patient survivability. The presence of H.
      pylori enhanced the risk in individuals with IL-1beta rs1143627:CC and rs16944:TT
      genotypes. Further, meta-analysis revealed significant association of IL-1beta
      rs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18-14.65) and rs16944: C > T (p
      = 0.01; OR = 5.49; 95% CI 1.48-20.37) in presence of H. pylori with gastric
      cancer in Asian population though no significant difference (p > 0.05) was found
      when compared to absence of H. pylori Environ. Mol. Mutagen. 59:653-667, 2018.
      (c) 2018 Wiley Periodicals, Inc.

PMID- 30094864
TI  - Organochlorines, perfluoroalkyl substances, mercury, and egg incubation
      temperature in an Arctic seabird: Insights from data loggers.
AB  - In birds, incubation-related behaviors and brood patch formation are influenced
      by hormonal regulation such as prolactin secretion. Brood patch provides
      efficient heat transfer between the incubating parent and the developing embryo
      in the egg. Importantly, several environmental contaminants are already known to
      have adverse effects on avian reproduction. However, relatively little is known
      about the effect of contaminants on incubation temperature (Tinc ) in wild birds.
      By using temperature thermistors placed into artificial eggs, we investigated
      whether the most contaminated parent birds are less able to provide appropriate
      egg warming and thus less committed to incubating their clutch. Specifically, we
      investigated the relationships among 3 groups of contaminants (organochlorines,
      perfluoroalkyl substances [PFASs], and mercury [Hg]) with Tinc and also with
      prolactin concentrations and brood patch size in incubating Arctic black-legged
      kittiwakes (Rissa tridactyla). Our results reveal that among the organochlorines
      considered, only blood levels of oxychlordane, the main metabolite of chlordane,
      a banned pesticide, were negatively related to the minimum incubation temperature
      in male kittiwakes. Levels of PFASs and Hg were unrelated to Tinc in kittiwakes.
      Moreover, our study suggests a possible underlying mechanism: since we reported a
      significant and negative association between blood oxychlordane concentrations
      and the size of the brood patch in males. Finally, this reduced Tinc in the most
      oxychlordane-contaminated kittiwakes was associated with a lower egg hatching
      probability. Environ Toxicol Chem 2018;37:2881-2894. (c) 2018 SETAC.

PMID- 30094866
TI  - Challenges in the management of the transgender patient with sickle cell disease.

PMID- 30094867
TI  - The gut microbiome and aquatic toxicology: An emerging concept for environmental
      health.
AB  - The microbiome plays an essential role in the health and onset of diseases in all
      animals, including humans. The microbiome has emerged as a central theme in
      environmental toxicology because microbes interact with the host immune system in
      addition to its role in chemical detoxification. Pathophysiological changes in
      the gastrointestinal tissue caused by ingested chemicals and metabolites
      generated from microbial biodegradation can lead to systemic adverse effects. The
      present critical review dissects what we know about the impacts of environmental
      contaminants on the microbiome of aquatic species, with special emphasis on the
      gut microbiome. We highlight some of the known major gut epithelium proteins in
      vertebrate hosts that are targets for chemical perturbation, proteins that also
      directly cross-talk with the microbiome. These proteins may act as molecular
      initiators for altered gut function, and we propose a general framework for an
      adverse outcome pathway that considers gut dysbiosis as a major contributing
      factor to adverse apical endpoints. We present 2 case studies, nanomaterials and
      hydrocarbons, with special emphasis on the Deepwater Horizon oil spill, to
      illustrate how investigations into the microbiome can improve understanding of
      adverse outcomes. Lastly, we present strategies to functionally relate chemical
      induced gut dysbiosis with adverse outcomes because this is required to
      demonstrate cause-effect relationships. Further investigations into the toxicant
      microbiome relationship may prove to be a major breakthrough for improving animal
      and human health. Environ Toxicol Chem 2018;37:2758-2775. (c) 2018 SETAC.

PMID- 30094868
TI  - Sensitivity of multiple life stages of 2 freshwater mussel species (Unionidae) to
      various pesticides detected in Ontario (Canada) surface waters.
AB  - Freshwater mussels contribute important ecological functions to aquatic systems.
      The water filtered by mussel assemblages can improve water quality, and the
      mixing of sediments by burrowing mussels can improve oxygen content and release
      nutrients. However, nearly 70% of North American freshwater mussel species are
      listed as either endangered, threatened, or in decline. In Ontario, 28 species
      are in decline or in need of protection. Even though freshwater mussels have a
      heightened sensitivity to some contaminants, few studies have investigated the
      risks that various pesticide classes pose to one freshwater mussel species or
      among life stages. Lampsilis siliquoidea and Villosa iris were the focus of the
      present study, with the latter currently listed as of "special concern" in
      Canada. A potential risk to the recovery of freshwater mussel species is the
      presence and persistence of pesticides in Ontario surface waters. Acute (48 h)
      toxicity tests were performed with V. iris glochidia to determine the effect on
      viability (surrogate for survival) following exposure to 4 fungicides
      (azoxystrobin, boscalid, metalaxyl, and myclobutanil), 3 neonicotinoids
      (clothianidin, imidacloprid, and thiamethoxam), 2 carbamates (carbaryl and
      malathion), 1 organophosphate (chlorpyrifos), and 1 butenolide (flupyradifurone).
      Juvenile and adult L. siliquoidea were also exposed to azoxystrobin,
      clothianidin, imidacloprid (juvenile only), and carbaryl (adult only). Our study
      found in general that all life stages were insensitive to the pesticides tested,
      with median effect and lethal concentrations >161 ug/L. The pesticides tested
      likely represent a minimal risk (hazard quotients <5.4 * 10-3 ) to freshwater
      mussel viability and survival in acute (48 h) and subchronic (28 d) exposures,
      respectively, in Ontario streams where pesticide concentrations were considerably
      lower than those tested in the present study. Environ Toxicol Chem 2018;37:2871
      2880. (c) 2018 SETAC.

PMID- 30094869
TI  - Paediatric pulled elbow injury: more common and recurrent than you think.

PMID- 30094871
TI  - Boundaries of frequency and treatment time in conventional hemodialysis:
      Balancing convenience, economics, and health outcomes.
AB  - Since the inception of hemodialysis (HD) for patients with chronic kidney
      disease, the "perfect" dialysis prescription has remained elusive. Part of this
      may relate to the heterogeneity among populations, individual patients, and
      differences in access to health provision. The optimal balance between dialysis
      frequency and duration to achieve reductions in patient morbidity and mortality
      continues to be debated. The concept of dialysis adequacy originated from a post
      hoc mathematical analysis of the National Cooperative Study and has evolved to
      become a way of calculating dialysis dose and standardizing the dialysis
      prescription. In contrast, in its originally conceived sense, dialysis adequacy
      referred to the effective clearance of small solutes. Given the evolution of
      dialysis practice, we now aim to consider dialysis adequacy in a broader and more
      holistic manner particularly in view of our aging population and focus toward
      important patient-centered outcomes. While the traditional thrice weekly, HD
      regimen remains the default renal replacement modality, alternative strategies
      including short daily HD, long conventional HD, and long nocturnal HD are being
      widely implemented. We aim for optimal solute clearance, effective
      ultrafiltration to achieve normotension (while avoiding intradialytic symptoms)
      and maintenance of nutritional parameters all within the caveat that quality of
      life and autonomy are preserved.

PMID- 30094870
TI  - Duvelisib, an oral dual PI3K-delta,gamma inhibitor, shows clinical and
      pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic
      lymphoma in a phase 1 study.
AB  - Duvelisib (IPI-145), an oral, dual inhibitor of phosphoinositide-3-kinase (PI3K)
      delta and -gamma, was evaluated in a Phase 1 study in advanced hematologic
      malignancies, which included expansion cohorts in relapsed/refractory (RR)
      chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and treatment
      naive (TN) CLL. Per protocol, TN patients were at least 65 years old or had a
      del(17p)/TP53 mutation. Duvelisib was administered twice daily (BID) in 28-day
      cycles at doses of 8-75 mg in RR patients (n = 55) and 25 mg in TN patients (n =
      18.) Diarrhea was the most common nonhematologic AE (TN 78%, RR 47%);
      transaminase elevations the most frequent lab-abnormality AE (TN 33.3%, RR
      30.9%); and neutropenia the most common >=grade 3 AE (RR 44%, TN 33%). The
      overall response rates were 56.4% for RR patients (1.8% CR, 54.5% PR) and 83.3%
      for TN patients (all PRs); median response duration was 21.0 months in RR
      patients but was not reached for TN patients. Based upon phase 1 efficacy,
      pharmacodynamics, and safety, duvelisib 25 mg BID was selected for further
      investigation in a phase 3 study in RR CLL/SLL.

PMID- 30094873
TI  - Assisted gene expression-based clustering with AWNCut.
AB  - In the research on complex diseases, gene expression (GE) data have been
      extensively used for clustering samples. The clusters so generated can serve as
      the basis for disease subtype identification, risk stratification, and many other
      purposes. With the small sample sizes of genetic profiling studies and noisy
      nature of GE data, clustering analysis results are often unsatisfactory. In the
      most recent studies, a prominent trend is to conduct multidimensional profiling,
      which collects data on GEs and their regulators (copy number alterations,
      microRNAs, methylation, etc.) on the same subjects. With the regulation
      relationships, regulators contain important information on the properties of GEs.
      We develop a novel assisted clustering method, which effectively uses regulator
      information to improve clustering analysis using GE data. To account for the fact
      that not all GEs are informative, we propose a weighted strategy, where the
      weights are determined data-dependently and can discriminate informative GEs from
      noises. The proposed method is built on the NCut technique and effectively
      realized using a simulated annealing algorithm. Simulations demonstrate that it
      can well outperform multiple direct competitors. In the analysis of TCGA
      cutaneous melanoma and lung adenocarcinoma data, biologically sensible findings
      different from the alternatives are made.

PMID- 30094872
TI  - Indirect monitoring of TORC1 signalling pathway reveals molecular diversity among
      different yeast strains.
AB  - Saccharomyces cerevisiae is the main species responsible for the alcoholic
      fermentation in wine production. One of the main problems in this process is the
      deficiency of nitrogen sources in the grape must, which can lead to stuck or
      sluggish fermentations. Currently, yeast nitrogen consumption and metabolism are
      under active inquiry, with emphasis on the study of the TORC1 signalling pathway,
      given its central role responding to nitrogen availability and influencing growth
      and cell metabolism. However, the mechanism by which different nitrogen sources
      activates TORC1 is not completely understood. Existing methods to evaluate TORC1
      activation by nitrogen sources are time-consuming, making difficult the analyses
      of large numbers of strains. In this work, a new indirect method for monitoring
      TORC1 pathway was developed on the basis of the luciferase reporter gene
      controlled by the promoter region of RPL26A gene, a gene known to be expressed
      upon TORC1 activation. The method was tested in strains representative of the
      clean lineages described so far in S. cerevisiae. The activation of the TORC1
      pathway by a proline-to-glutamine upshift was indirectly evaluated using our
      system and the traditional direct methods based on immunoblot (Sch9 and Rps6
      phosphorylation). Regardless of the different molecular readouts obtained with
      both methodologies, the general results showed a wide phenotypic variation
      between the representative strains analysed. Altogether, this easy-to-use assay
      opens the possibility to study the molecular basis for the differential TORC1
      pathway activation, allowing to interrogate a larger number of strains in the
      context of nitrogen metabolism phenotypic differences.

PMID- 30094875
TI  - "Therapeutic applications of the 'NPGP' family of viral 2As".
AB  - Oligopeptide "2A" and "2A-like" sequences ("2As"; 18-25aa) are found in a range
      of RNA virus genomes controlling protein biogenesis through "recoding" of the
      host-cell translational apparatus. Insertion of multiple 2As within a single open
      reading frame (ORF) produces multiple proteins; hence, 2As have been used in a
      very wide range of biotechnological and biomedical applications. During
      translation, these 2A peptide sequences mediate a eukaryote-specific, self
      "cleaving" event, termed "ribosome skipping" with very high efficiency. A
      particular advantage of using 2As is the ability to simultaneously translate a
      number of proteins at an equal level in all eukaryotic systems although,
      naturally, final steady-state levels depend upon other factors-notably protein
      stability. By contrast, the use of internal ribosome entry site elements for co
      expression results in an unbalanced expression due to the relative inefficiency
      of internal initiation. For example, a 1:1 ratio is of particular importance for
      the biosynthesis of the heavy-chain and light-chain components of antibodies:
      highly valuable as therapeutic proteins. Furthermore, each component of these
      "artificial polyprotein" systems can be independently targeted to different sub
      cellular sites. The potential of this system was vividly demonstrated by
      concatenating multiple gene sequences, linked via 2A sequences, into a single,
      long, ORF-a polycistronic construct. Here, ORFs comprising the biosynthetic
      pathways for violacein (five gene sequences) and beta-carotene (four gene
      sequences) were concatenated into a single cistron such that all components were
      co-expressed in the yeast Pichia pastoris. In this review, we provide useful
      information on 2As to serve as a guide for future utilities of this co-expression
      technology in basic research, biotechnology, and clinical applications.

PMID- 30094874
TI  - Prediction of peripheral nerve stimulation thresholds of MRI gradient coils using
      coupled electromagnetic and neurodynamic simulations.
AB  - PURPOSE: As gradient performance increases, peripheral nerve stimulation (PNS) is
      becoming a significant constraint for fast MRI. Despite its impact, PNS is not
      directly included in the coil design process. Instead, the PNS characteristics of
      a gradient are assessed on healthy subjects after prototype construction. We
      attempt to develop a tool to inform coil design by predicting the PNS thresholds
      and activation locations in the human body using electromagnetic field
      simulations coupled to a neurodynamic model. We validate the approach by
      comparing simulated and experimentally determined thresholds for 3 gradient
      coils. METHODS: We first compute the electric field induced by the switching
      fields within a detailed electromagnetic body model, which includes a detailed
      atlas of peripheral nerves. We then calculate potential changes along the nerves
      and evaluate their response using a neurodynamic model. Both a male and female
      body model are used to study 2 body gradients and 1 head gradient. RESULTS: There
      was good agreement between the average simulated thresholds of the male and
      female models with the experimental average (normalized root-mean-square error:
      <10% and <5% in most cases). The simulation could also interrogate thresholds
      above those accessible by the experimental setup and allowed identification of
      the site of stimulation. CONCLUSIONS: Our simulation framework allows accurate
      prediction of gradient coil PNS thresholds and provides detailed information on
      location and "next nerve" thresholds that are not available experimentally. As
      such, we hope that PNS simulations can have a potential role in the design phase
      of high performance MRI gradient coils.

PMID- 30094876
TI  - CASC2: An emerging tumour-suppressing long noncoding RNA in human cancers and
      melanoma.
AB  - Deregulation of long noncoding RNAs (lncRNAs) has been implicated in
      tumourigenesis. Cancer Susceptibility Candidate 2 (CASC2) is a lncRNA
      downregulated in multiple cancer types, including endometrial, lung, gastric and
      colorectal cancers. CASC2 functions as a tumour-suppressive lncRNA though
      multiple mechanisms, such as sequestration of oncogenic microRNAs and repression
      of Wnt/beta-catenin signalling. Pertinent to clinical practice, the use of CASC2
      as a prognostic marker has been demonstrated in sporadic studies. These findings
      suggested that CASC2 might play an important role in human cancers and melanoma.
      More efforts are warranted to examine the function role of CASC2 in other cancer
      types. Further validation is also needed to promote its development to be a
      clinically utilizable prognostic biomarker.

PMID- 30094878
TI  - Who pays for the medical costs of obesity? New evidence from the employer
      mandate.
AB  - Theory suggests that the medical costs of obesity should be passed on to obese
      workers, in the form of lower wages, whenever health coverage is a part of
      employee compensation. In contrast to existing work on this topic, this paper
      illustrates that the medical expenditures caused by obesity among working adults
      are relatively small and that wage offsets should therefore be difficult to
      detect. The paper supports this claim by exploiting the variation provided by the
      Affordable Care Act's employer mandate. Findings suggest that obese workers tend
      to bear the approximate cost of their medical expenditures via lower wages.
      However, the observed effects are often insignificantly different from zero.

PMID- 30094877
TI  - Evaluation of national guidelines for bronchiolitis: AGREEments and
      controversies.
AB  - AIM: Bronchiolitis is a common respiratory illness and is a leading cause of
      hospitalisation in infancy. We aimed to appraise three recent national
      bronchiolitis guidelines produced by the Australasian Paediatric Research in
      Emergency Departments International Collaborative, the National Institute for
      Health and Care Excellence in the UK and the American Academy of Pediatrics.
      METHODS: A group of final-year medical students and one senior clinician used the
      AGREE II tool to appraise each guideline in two stages. First, two students
      appraised each guideline independently and presented their results. Second, two
      self-selected students met with the senior clinicians to review all scores to
      ensure completeness of the appraisal and consistency of AGREE II application.
      RESULTS: The guidelines scored well overall, with particular strengths in the
      domains of clarity of presentation, scope and purpose and rigour of development.
      Comparison of the recommendations across each guideline demonstrated a high
      degree of consistency. Notable differences included recommendations for the role
      of palivizumab in prevention of bronchiolitis, the use of continuous pulse
      oximetry monitoring in the hospitalised patient and the value of respiratory
      virus testing. CONCLUSIONS: Our appraisal of bronchiolitis guidelines from three
      high-income countries demonstrated that they were of high quality, with
      substantial areas of agreement. Most aspects of clinical practice should be
      uniform for this common paediatric condition. Areas of guideline weakness were in
      the domains of applicability and editorial independence. We identified three
      areas of controversy where further research is needed to support stronger
      evidence-based recommendations.

PMID- 30094879
TI  - Ionic Donor-Acceptor Chain Derived from an Electron-Transfer Reaction of a
      Paddlewheel-Type Diruthenium(II, II) Complex and N,N'-Dicyanoquinonediimine.
AB  - A new ionic donor-acceptor (D+ A- ) chain compound, [{Ru2 (2,6-(CF3 )2 PhCO2 )2
      (p-PhPhCO2 )2 }DMDCNQI] (1; 2,6-(CF3 )2 PhCO2- =2,6-bis(trifluoromethyl)benzoate;
      p-PhPhCO2- =4-biphenylcarboxylate; DMDCNQI=2,5-dimethyl-N,N'
      dicyanoquinonediimine) was isolated and structurally characterized. It represents
      the first of this type of ionic chain compounds.

PMID- 30094880
TI  - Analysis of factors related to the occurrence of important drug-specific
      postmarketing safety-related regulatory actions: A cohort study focused on first
      in-class drugs.
AB  - PURPOSE: First-in-class (FIC) drugs with novel modes of action pose concerns
      regarding important postmarketing safety issues. The purpose of this study was to
      analyze the factors related to the occurrence of postmarketing safety-related
      regulatory actions (PSRAs) for drugs approved in the United States (US), with a
      focus on FIC drugs. METHODS: New molecular entities and new therapeutic biologics
      approved in the United States between 1 January 2003 and 31 December 2013 were
      included in the analysis. Important drug-specific PSRAs were defined as market
      withdrawal or the addition of new black box warnings or warnings due to adverse
      drug reactions. The relationship between baseline characteristics and the
      occurrence of important drug-specific PSRAs was investigated using a multivariate
      logistic regression model. We also defined the event as the first important PSRA
      and estimated the time-to-event for each factor. RESULTS: ATC category L
      (antineoplastic and immunomodulating agents) and FIC drug classification were
      shown to be statistically significant factors, with odds ratios of 2.15 (95% CI:
      1.12-4.11; P = 0.0203) and 1.87 (95% CI: 1.06-3.31; P = 0.0309), respectively.
      ATC category L and FIC drugs were also significant factors for time to occurrence
      of the first event. CONCLUSION: FIC designation and ATC category L were
      identified as factors related to important drug-specific PSRAs. These factors
      were also associated with the time to occurrence of the first important drug
      specific PSRAs.

PMID- 30094881
TI  - Charge-Transfer Salts of 6,6-Dicyanopentafulvenes: From Topology to Charge
      Separation in Solution.
AB  - 6,6-Dicyanopentafulvene derivatives and metallocenes with redox potentials
      appropriate for forming their radical anions form highly persistent donor
      acceptor salts. The charge-transfer salts of 2,3,4,5-tetraphenyl-6,6
      dicyanofulvene with cobaltocene (1?Cp2 Co) and 2,3,4,5
      tetrakis(triisopropylsilyl)-6,6-dicyanofulvene with decamethylferrocene (2?Fc*)
      have been prepared. The X-ray structures of the two salts, formed as black
      plates, were obtained and are discussed herein. Compared with neutral
      dicyanopentafulvenes, the chromophores in the metallocene salts show substantial
      changes in bond lengths and torsional angles in the solid state. EPR, NMR, and
      optical spectroscopy, as well as superconducting quantum interference device
      (SQUID) measurements, reveal that charge-separation in the crystalline states and
      in frozen and fluid solutions depends on subtle differences of redox potentials,
      geometry, and on ion pairing. Whereas 1?Cp2 Co reveals paramagnetic character in
      the crystalline state and in solution, compound 2?Fc* shows a delicate balance
      between para- and diamagnetism, depending on the temperature and solvent
      characteristics.

PMID- 30094882
TI  - FBXW7 suppresses epithelial-mesenchymal transition and chemo-resistance of non
      small-cell lung cancer cells by targeting snai1 for ubiquitin-dependent
      degradation.
AB  - OBJECTIVES: FBXW7 acts as a tumour suppressor by targeting at various
      oncoproteins for ubiquitin-mediated degradation. However, the clinical
      significance and the involving regulatory mechanisms of FBXW7 manipulation of
      NSCLC regeneration and therapy response are not clear. MATERIALS AND METHODS:
      Immunohistochemical staining and qRT-PCR were applied to detect FBXW7 and Snai1
      expression in 100 samples of NSCLC and matched tumour-adjacent tissues. FBXW7
      manipulation of cancer biological functions were studied by using MTT assay,
      immunoblotting, flow cytometry, transwells, wound healing assay, and sphere
      formation assays. Immunofluorescence and co-immunoprecipitation were used to
      analyse the possible interaction between Snai1 and FBXW7. RESULTS: We detected
      the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7
      level was correlated with advanced TNM stage. Furthermore, those patients with
      decreased FBXW7 expression tend to have both poorer 5-year survival outcomes, and
      shorter disease-free survival, comparing to those with higher FBXW7 levels.
      Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by
      inducing cell growth arrest, increasing chemo-sensitivity and inhibiting
      Epithelial-mesenchymal Transition (EMT) progress. Results further showed that
      FBXW7 could interact with Snai1 directly to degrade its expression through
      ubiquitylating alternation in NSCLC, which could be partially abrogated by
      restoring Snai1 expression. CONCLUSIONS: FBXW7 conduction of tumour suppression
      was partly through degrading Snai1 directly for ubiquitylating regulation in
      NSCLC.

PMID- 30094883
TI  - Two Pairs of Chiral "Tower-Like" Ln4 Cr4 (Ln=Gd, Dy) Clusters: Syntheses,
      Structure, and Magnetocaloric Effect.
AB  - Two pairs of novel chiral chromium lanthanide compounds, formulated as l- and d
      [Gd4 Cr4 (IN)10 (MU3 -OH)4 (MU4 -O)4 (H2 O)12 ]?[IN]2 ?8 H2 O (1 and 3), and l-
      and d-[Dy4 Cr4 (IN)11 (MU3 -OH)4 (MU4 -O)4 (H2 O)8 ]?[IN]?1.5 H2 O (2 and 4)
      (HIN=isonicotinic acid) have been successfully synthesized and characterized.
      Structural analysis reveals that four Ln3+ ions and four Cr3+ ions connect with
      each other and yield a "tower-like" [Ln4 Cr4 ] skeleton. Apart from the above
      featuring an aesthetically charming structure, circular dichroism (CD) spectra
      confirm that compounds 1 and 3, 2 and 4 are enantiomers. To the best of our
      knowledge, these are the largest chiral chromium lanthanide compounds. In
      addition, magnetic interaction shows that Gd (the mixture of 1 and 3) exhibits
      significant cryogenic magnetocaloric effect (MCE) with -DeltaSm =18.08 J kg-1  K
      1 (34.69 mJ cm-3  K-1 ). Also, the observed second-harmonic generation
      efficiencies of [Gd4 Cr4 (IN)10 (MU3 -OH)4 (MU4 -O)4 (H2 O)12 ]?[IN]2 ?8 H2 O and
      [Dy4 Cr4 (IN)11 (MU3 -OH)4 (MU4 -O)4 (H2 O)8 ]?[IN]?1.5 H2 O are 0.3 and 0.4
      times that of urea, respectively.

PMID- 30094884
TI  - Successful laparotomy tumor resection and levonorgestrel-releasing intrauterine
      system for atypical polypoid adenomyoma.
AB  - Hysteroscopic transcervical resection (TCR) is often performed as fertility
      sparing treatment for atypical polypoid adenomyoma (APA) patients. However, TCR
      has the risk of uterine wall perforation, especially when the tumor extends
      deeply into the uterine muscle layer. We report an APA patient in whom it was
      impossible to completely resect the tumor by TCR, but laparotomy tumor resection
      followed by levonorgestrel-releasing intrauterine system (LNG-IUS) was
      successful. The patient was a 35-year-old nulligravida woman. We performed
      laparotomy tumor resection and inserted the LNG-IUS into uterine cavity just
      after surgery. Microscopic residual tumor was suspected based on
      histopathological findings. However, the patient has not relapsed for 26 months,
      even though the LNG-IUS was removed after 6 months. Laparotomy tumor resection
      may be one fertility sparing treatment option for APA patients. Furthermore, it
      may be effective to use the LNG-IUS after surgery for two purposes that are
      adhesion prevention and tumor disappearance.

PMID- 30094885
TI  - Effect of vaginal washing before intravaginal dinoprostone insertion for labor
      induction: A randomized clinical trial.
AB  - AIM: Prostaglandins have a dual action of cervical ripening and induction of
      uterine contraction. This study was designed to compare the effectiveness of
      vaginal washing just before insertion of intravaginal dinoprostone. METHODS: A
      randomized controlled trial was conducted at the Zeynep Kamil Women and
      Children's Health Training and Research Hospital. One hundred and ninety-one
      women with singleton, term pregnancy who underwent labor induction were randomly
      assigned to two groups: Group 1 consisted of 95 pregnant women with vaginal
      washing before intravaginal dinoprostone (Propess system for slow release system
      of 10 mg of dinoprostone) insertion (study group), and 96 pregnant women
      constituted the control group who did not undergo vaginal washing before
      intravaginal dinoprostone insertion. A parallel randomized controlled trial was
      conducted with an allocation ratio of 1:1 to compare the effectiveness of vaginal
      washing before intravaginal dinoprostone insertion. RESULTS: The groups had
      similar mean age, body mass index, gestational age, gravidity, parity and Bishop
      score before agent insertion (P > 0.05). Duration of dinoprostone kept
      intravaginally, duration from the beginning of dinoprostone insert vaginally to
      the active phase of labor and duration from the time of intravaginal dinoprostone
      insertion to delivery were significantly longer in the control group (P < 0.05).
      Uterine hyperstimulation rate was significantly higher in study group compared to
      control group (P < 0.05). Meconium passage, fetal infection and neonatal
      intensive care unit admission were significantly higher in the control group (P <
      0.05). CONCLUSION: Vaginal washing before intravaginal dinoprostone insertion may
      increase Prostaglandin E2 bioavailability as we found shorter duration and better
      outcome of labor induction in the present study.

PMID- 30094886
TI  - ISPAD Clinical Practice Consensus Guidelines 2018: Management of cystic fibrosis
      related diabetes in children and adolescents.

PMID- 30094887
TI  - p16/Ki67 dual staining improves the detection specificity of high-grade cervical
      lesions.
AB  - AIM: The goal of this study was to analyze the specificity of p16/Ki67 dual
      staining in the detection of high-grade cervical lesions. METHODS: A total of 223
      patients with an average age of 39 years old were enrolled in this study. All
      samples were analyzed by p16/Ki67 immunocytochemical dual staining, liquid-based
      cytology and high-risk human papillomavirus (HR-HPV) test. Diagnosis of each
      patient was verified by histopathological test. RESULTS: The specificity of
      p16/Ki67 dual staining was 68.33%, which was significantly higher than that of
      cytology (38.33%) and HR-HPV test (21.67%) (P < 0.05) for CIN2+ detection.
      p16/Ki67 dual staining had similar sensitivity with HR-HPV test for CIN2+
      detection (90.18% vs 93.87%, P = 0.286). In atypical squamous cells of
      undetermined significance (ASC-US) and low-grade squamous intraepithelial lesion
      (LSIL) cases, the specificity of p16/Ki67 dual staining was significantly higher
      than that of HPV test (66.67% vs 3.70%, P < 0.05) and its sensitivity was similar
      to that of HPV test for CIN2+ detection. The sensitivity and specificity of dual
      staining for CIN2+ detection in HR-HPV positive women were 90.85% and 70.21%,
      respectively, which were higher than those of cytology (83.01% and 42.55%) and
      HPV16/18 test (70.59% and 44.68%). CONCLUSIONS: p16/Ki67 dual staining could
      improve the specificity of high-grade cervical lesions detection and have similar
      sensitivity to HPV test for CIN2+ detection. When triaging women with ASC-US or
      LSIL liquid-based cytology, compared with positive HR-HPV, the specificity of
      CIN2+ lesion detection was increased by p16/Ki67 dual staining. p16/Ki67 dual
      staining could reduce colposcopy referrals and avoid excessive diagnosis and
      treatment.

PMID- 30094888
TI  - Day by day, hour by hour: Naturalistic language input to infants.
AB  - Measurements of infants' quotidian experiences provide critical information about
      early development. However, the role of sampling methods in providing these
      measurements is rarely examined. Here we directly compare language input from
      hour-long video-recordings and daylong audio-recordings within the same group of
      44 infants at 6 and 7 months. We compared 12 measures of language quantity and
      lexical diversity, talker variability, utterance-type, and object presence,
      finding moderate correlations across recording-types. However, video-recordings
      generally featured far denser noun input across these measures compared to the
      daylong audio-recordings, more akin to 'peak' audio hours (though not as high in
      talkers and word-types). Although audio-recordings captured ~10 times more awake
      time than videos, the noun input in them was only 2-4 times greater. Notably,
      whether we compared videos to daylong audio-recordings or peak audio times,
      videos featured relatively fewer declaratives and more questions; furthermore,
      the most common video-recorded nouns were less consistent across families than
      the top audio-recording nouns were. Thus, hour-long videos and daylong audio
      recordings revealed fairly divergent pictures of the language infants hear and
      learn from in their daily lives. We suggest that short video-recordings provide a
      dense and somewhat different sample of infants' language experiences, rather than
      a typical one, and should be used cautiously for extrapolation about common
      words, talkers, utterance-types, and contexts at larger timescales. If theories
      of language development are to be held accountable to 'facts on the ground' from
      observational data, greater care is needed to unpack the ramifications of
      sampling methods of early language input.

PMID- 30094889
TI  - Food addiction and other addictive behaviours in bariatric surgery candidates.
AB  - OBJECTIVE: The present study investigated the association between food addiction
      (FA) and other addictive behaviours in 216 bariatric surgery candidates (91.7%
      class 3 obesity; 80.1% women; age Mdn = 44.00 years, range 18-73). METHOD:
      Assessment included the Yale Food Addiction Scale 2.0 (YFAS 2.0) and standardized
      self-report questionnaires to measure symptoms of disorders related to substance
      use (alcohol and nicotine) and behavioural addictions (gambling, Internet-use,
      buying, hypersexual disorders, and exercise dependence). RESULTS: Bivariate
      correlations indicated a moderate relationship of YFAS 2.0 FA symptoms with
      buying disorder symptoms and a weak association with Internet-use disorder
      symptoms. Fifty-nine patients (27.3%) met the YFAS 2.0 threshold for FA, 1.9% for
      alcohol use disorder, 6.0% for nicotine use disorder, 17.3% for buying disorder,
      2.3% for Internet-use disorder, and 1.4% for hypersexual disorder. None of the
      patients scored above the respective questionnaire thresholds for gambling
      disorder or exercise dependence. Patients with versus without YFAS 2.0 FA
      diagnosis did not differ with regard to prevalence estimates of addictive
      behaviours. CONCLUSIONS: Clinical implications and potential limitations of the
      findings are discussed. Future studies should address the potential risk of
      postoperative addiction transfer using long-term follow-ups and controlled study
      designs.

PMID- 30094890
TI  - Quantifying Cognitive Dysfunction Across the Spectrum of End Stage Kidney Disease
      - A Systematic Review and Meta-Analysis.
AB  - IMPORTANCE: Cognitive dysfunction is reportedly highly prevalent among chronic
      kidney disease (CKD) patients. A variety of screening tools and neuropsychiatric
      batteries are utilized to quantify the magnitude and nature of this dysfunction
      in CKD patients. OBJECTIVE: To summarize the neurocognitive testing used and
      determine what degree cognitive dysfunction is reported in CKD patients. METHODS:
      Articles published in English containing consenting age of majority participants
      who were either: pre-dialysis patients, hemodialysis (HD) or peritoneal dialysis
      (PD) patients, or renal transplant recipients were considered. If comparative non
      CKD control participants were reported, this data was also collected. All study
      designs were included. The search period encompassed articles from 1980 until May
      2018. This review is registered with PROSPERO (CRD42018096568). RESULTS: Of the
      1,711 articles screened, 148 articles were relevant and used in the meta
      analysis. Commonly used assessments were: The Mini-Mental State Examination
      (MMSE), The Modified Mini-Mental State Examination (3MS), the Trails Making Tests
      (TMT) forms A and B, and components of the Wechsler Adult Intelligence Scale:
      Digit Span and Digit Symbol. The means for all assessments were adjusted using a
      random effects model to account for the differences in variance. Adjusted mean
      MMSE scores were significantly lower for both pre-dialysis (26.08, n=17,073) and
      HD (26.31, n=3,314) patients when compared to non-CKD controls (28.21, n=5,226).
      PD (58.01 seconds, n=859) and HD (56.04 seconds, n=2,344) patients also took
      significantly longer to complete the TMT-A than non-CKD controls (37.62 seconds,
      n=4,809). CONCLUSIONS: Patients with CKD, especially pre-dialysis and those
      requiring dialysis, are likely to exhibit impairments in cognition that can be
      identified with specific screening neuropsychological assessments. This article
      is protected by copyright. All rights reserved.

PMID- 30094891
TI  - Daily motor characteristics in children with developmental coordination disorder
      and in children with specific learning disorder.
AB  - An association between learning disorders and coordination problems has been
      reported in several studies over the last few decades. In this study, we have
      investigated daily motor characteristics in children with a diagnosis of specific
      learning disorder (SLD) and compared them with those of children with
      developmental coordination disorder (DCD) and those of typically developing
      controls. Ninety-six children aged 5 to 12 years were included: 29 with a
      diagnosis of SLD, 33 of DCD, and 34 controls. The Italian version of the
      Developmental Coordination Disorder Questionnaire 2007 (DCDQ-Italian) was used to
      measure children's coordination in everyday functional activities. The mean DCDQ
      Italian total score was significantly lower in both SLD and DCD groups as
      compared with controls. Regarding subscores, both clinical groups scored
      significantly lower than controls on "Fine motor/handwriting" skills and on
      "General coordination." The DCD group scored also significantly lower than
      controls on "Control during movement." Moreover, clinical groups differed from
      each other, with SLD children scoring significantly higher on "Control during
      movement" and "General coordination" subscores. SLD children diverged from
      typically developing children in some motor skills during ordinary activities,
      and although this discrepancy was not as severe as in DCD children, it could have
      an impact on self-esteem and sport inclusion.

PMID- 30094892
TI  - Self-Propelled Nanomotors for Thermomechanically Percolating Cell Membranes.
AB  - We report a near-infrared (NIR) light-powered Janus mesoporous silica nanomotor
      (JMSNM) with macrophage cell membrane (MPCM) cloaking that can actively seek
      cancer cells and thermomechanically percolate cell membrane. Upon exposure to NIR
      light, a heat gradient across the Janus boundary of the JMSNMs is generated by
      the photothermal effect of the Au half-shells, resulting in a self-thermophoretic
      force that propels the JMSNMs. In biological medium, the MPCM camouflaging can
      not only prevent dissociative biological blocks from adhering to JMSNMs but also
      improve the seeking sensitivity of the nanomotors by specifically recognizing
      cancer cells. The biofriendly propulsion and recognition capability enable JMSNMs
      to achieve the active seeking and bind to the membrane of cancer cells.
      Subsequent illumination with NIR then triggers the photothermal effect of
      MPCM@JMSNMs to thermomechanically perforate the cytomembranes for guest molecular
      injection. This approach integrates the functions of active seeking,
      cytomembranes perforating, and thermomechanical therapy in nanomotors, which may
      pave the way to apply self-propelled motors in biomedical fields.

PMID- 30094894
TI  - Relationship between brachycephalic airway syndrome and gastrointestinal signs in
      three breeds of dog.
AB  - OBJECTIVES: To assess the breed-specific prevalence of, and effects of corrective
      airway surgery on, gastrointestinal signs in French bulldogs, English bulldogs
      and pugs presenting with brachycephalic airway syndrome to a referral teaching
      hospital. MATERIALS AND METHODS: In this retrospective study, ptyalism,
      regurgitation and vomiting were graded at presentation using a previously
      established scoring system. Staphylectomy and nares resection were performed on
      all dogs. Gastrointestinal signs were re-assessed via telephone follow-up at
      least 6 weeks after surgery. RESULTS: Ninety-eight dogs were included: French
      bulldogs (n=43), English bulldogs (n=12) and pugs (n=43). Overall population
      prevalence of all gastrointestinal signs was 56%. Breed-specific prevalence for
      French bulldogs was 93%, English bulldogs 58% and pugs 16%. There was post
      surgical clinical improvement in gastrointestinal signs for the whole study
      population, especially in French bulldogs. CLINICAL SIGNIFICANCE: The prevalence
      of gastrointestinal signs in dogs presenting with brachycephalic airway syndrome
      and improvement in these clinical signs following corrective surgery may vary
      between breeds.

PMID- 30094893
TI  - Predictors of outcome among young adult patients with anorexia nervosa in a
      randomised controlled trial.
AB  - OBJECTIVE: The prognosis in cases of anorexia nervosa (AN) is unsatisfactory, and
      it is therefore important to examine pretreatment predictors of outcome. METHODS:
      Female AN patients (N = 74) included in a randomised controlled trial receiving
      individual cognitive behavioural therapy (CBT) or family-based treatment (FBT)
      were included. Predictors of the outcome were explored using pretreatment eating
      disorder psychopathology. RESULTS: In the CBT group, lower levels of emotional
      dysregulation and greater deficits in identifying and coping with inner states
      were predictors of weight increase, explaining 37.7% of the variance. In the FBT
      group, lower interoceptive deficits predicted an increase in weight (explaining
      17.7% of the variance), whereas bulimic behaviour (32.4%) and problems with
      emotional regulation (23.3%) were predictors of increased diagnostic symptoms.
      CONCLUSIONS: Bulimic symptoms and the ability to identify and cope with emotional
      states appear to be important aspects that should be addressed in the treatment
      of young adult patients with AN.

PMID- 30094895
TI  - Periodontal diseases and adverse pregnancy outcomes.
AB  - From last decade of the 20th century, numerous epidemiological studies and
      intervention trials have attempted to prove the relationships between maternal
      periodontal diseases and adverse pregnancy outcomes (APO). Periodontal diseases
      are considered a risk factor for APO, including preterm birth, fetal growth
      restriction, low birthweight, pre-eclampsia and gestational diabetes. However,
      the efficacy of periodontal treatment during pregnancy is controversial. Two
      pathogenic mechanisms might explain the potential effect of periodontal diseases
      on pregnancy outcomes. First, periodontal bacteria originating in the gingival
      biofilm directly affect the feto-placental unit subsequent to bacteremia. Second,
      inflammatory mediators secreted by the subgingival inflammatory site are carried
      to the feto-placental unit, where they then cause an inflammatory response. To
      elucidate these mechanisms, many researchers have been investigating the use of
      experimental animal models and in vitro models. In the present review, we
      summarize the current literature on the relationship between periodontal diseases
      and APO from epidemiological studies, animal models studies and in vitro studies,
      and speculate on the possible mechanism of periodontal diseases affecting
      pregnancy outcomes.

PMID- 30094896
TI  - Prognostic significance of microscopic tumor extension in local recurrence of
      myxofibrosarcoma and undifferentiated pleomorphic sarcoma.
AB  - Myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) frequently
      display infiltrative growth into the adjacent normal soft tissue. In this study,
      we aimed to determine whether the microscopic extension into surrounding normal
      tissue can influence the local recurrence of MFS and UPS. A total of 42 cases (22
      MFS and 20 UPS) were examined. The length of the microscopic extension was
      measured from the edge of the main tumor mass to the end of infiltration. The
      length of 5.5 mm was selected as the optimal cut-off value that could predict
      local recurrence using the receiver operating characteristic (ROC) curve and
      Youden index. Longer length of microscopic extension was significantly correlated
      with the status of resection margin (P = 0.032). The group with longer length of
      microscopic extension (>5.5 mm) had significantly worse recurrence-free survival
      than the group with shorter length of microscopic extension (<=5.5 mm) (P =
      0.000). Multivariate analysis revealed that the length of microscopic extension
      was independent predictors of recurrence-free survival (P = 0.018). In
      conclusion, microscopic extensions at the edge of the main mass into the
      surrounding normal tissue were observed in most MFS and UPS patients, and the
      length of microscopic extension was associated with local recurrence.

PMID- 30094897
TI  - Dedifferentiated liposarcoma of the spermatic cord with features of epithelioid
      rhabdomyosarcoma and a rapidly fatal outcome.

PMID- 30094898
TI  - Changes in the amount of sleep and daytime sleepiness: A follow-up study of
      schoolchildren from ages 10 to 15 years.
AB  - AIM: This study examines the amount of sleep and daytime sleepiness, and how
      these change in a follow-up cohort study of school-aged children. METHODS: A
      total of 1351 schoolchildren (aged 10) and their parents were invited to
      participate in the study and were studied again at ages 12 and 15 years. A survey
      put forth by the Health Behaviour of Schoolchildren research network was used.
      RESULTS: The amount of sleep during weekdays dropped significantly from age 10 to
      15. At weekends, the amount of sleep increased significantly. During weekdays,
      the proportion of children reporting having slept enough dropped from 71% at age
      10 to 19% at age 15. Frequent daytime sleepiness occurred in 13% of children at
      age 10 and increased to 24% at the age of 15. CONCLUSIONS: It is essential to
      promote adequate amount of sleep and prevent daytime sleepiness in children
      growing from age 10 to 15 years. Nurses and other health care professionals
      should systematically assess and promote healthy sleeping habits while caring for
      children between these ages.

PMID- 30094899
TI  - Direct Solar-to-Electrochemical Energy Storage in a Functionalized Covalent
      Organic Framework.
AB  - A covalent organic framework integrating naphthalenediimide and triphenylamine
      units (NT-COF) is presented. Two-dimensional porous nanosheets are packed with a
      high specific surface area of 1276 m2  g-1 . Photo/electrochemical measurements
      reveal the ultrahigh efficient intramolecular charge transfer from the TPA to the
      NDI and the highly reversible electrochemical reaction in NT-COF. There is a
      synergetic effect in NT-COF between the reversible electrochemical reaction and
      intramolecular charge transfer with enhanced solar energy efficiency and an
      accelerated electrochemical reaction. This synergetic mechanism provides the key
      basis for direct solar-to-electrochemical energy conversion/storage. With the NT
      COF as the cathode materials, a solar Li-ion battery is realized with decreased
      charge voltage (by 0.5 V), increased discharge voltage (by 0.5 V), and extra 38.7
      % battery efficiency.

PMID- 30094900
TI  - Neoplastic PD-L1 expression on interdigitating dendritic cell sarcoma: A
      supplementary study of a case report.

PMID- 30094901
TI  - Best intentions or best practice? A case study of the nutritional needs and
      outcomes of a person with dementia living in a residential aged care home.
AB  - AIMS: To evaluate the nutritional status and needs of a person with dementia
      living in an aged care home, including identification of barriers to, and
      effective strategies for, the provision of person-centred care. BACKGROUND:
      Nutrition and hydration care are integral to quality of life for adults with
      dementia, but there is little research on whether staff knowledge around
      effective care strategies for residents is translated into optimal care. DESIGN:
      Focused ethnographic single-case design. METHODS: The perspectives of the
      resident, her prime family member, and six care staff were triangulated through
      interviews, observation, document audit, and medical file review to investigate
      the resident's nutrition and hydration status and needs (October 2014-April
      2015). RESULTS: During 3 years in care, this resident had lost weight steadily.
      Staff appeared attentive but did not maintain a systematic record of body mass
      index. At meals, staff encouraged eating but used ineffective strategies. Food
      was not served in ways that facilitated active participation. Eating and drinking
      were structured as tasks to be completed rather than activities to be enjoyed.
      CONCLUSION: This instrumental case study identified a task-oriented, rather than
      person-centred, approach to nutrition and hydration care, adversely affecting the
      resident's nutritional health and capability to participate actively.

PMID- 30094902
TI  - Children bouncing to the emergency department: Changes in trampoline injury
      patterns.
AB  - AIM: To compare trampoline injuries and injury costs sustained at a commercial
      trampoline park versus private homes presenting to a major Australian children's
      hospital over a 12-month period. METHODS: Children presenting with a trampoline
      injury to the paediatric emergency department in 2015 were identified using a
      keyword search of triage information. A comparison of injuries sustained at a
      commercial trampoline park and private homes was performed. RESULTS: A total of
      392 children presented with injuries, and the majority of injuries (68.9%)
      occurred at a private home; 19.4% were from a commercial trampoline park.
      Significant differences were seen between patients from a private home and
      commercial park for median age (5.6 vs. 12.8 years; P < 0.001), gender (48.2 vs.
      61.8% female; P = 0.03) and season of injury. Of the injuries, 27.3% occurred
      when children fell off the trampoline, and fractures (39.5%) were the most common
      injury; 17.4% required hospital admission, and 12.8% required surgical
      intervention. Commercial park injuries had a significantly longer median length
      of stay (37.4 vs. 22.8 h; P = 0.03). The estimated total acute cost for these
      trampoline injuries in 1 year was $546 786. Commercial trampoline park injuries
      accounted for 21.7% of the estimated cost and private homes for 68.2%.
      CONCLUSIONS: Paediatric trampoline injuries remain a common source of hospital
      presentation and admission, despite the introduction of a Voluntary Australian
      Standard. Paediatric trampoline injuries usually occur in private homes; however,
      the increasing popularity of commercial trampoline parks contributes to a change
      in the profile of trampoline injuries. Commercial park injuries were more
      expensive to treat.

PMID- 30094903
TI  - Sublethal and transgenerational effects of thiamethoxam applied to cotton seed on
      Chrysoperla externa and Harmonia axyridis.
AB  - BACKGROUND: Thiamethoxam, when applied as a seed treatment, can contaminate plant
      products, such as extrafloral nectar, and have non-target effects on beneficial
      arthropods. This study assessed the non-target effects of thiamethoxam applied to
      cotton seed on the life history parameters of the predators Chrysoperla externa
      (Neuroptera: Chrysopidae) and Harmonia axyridis (Coleoptera: Coccinellidae).
      RESULTS: Exposure of C. externa larvae to plants grown from thiamethoxam-treated
      seeds caused sublethal and transgenerational effects. Thiamethoxam treatment
      doubled the proportion of pharate adults and reduced egg fertility in C. externa
      F0 and F1 generations. In addition, the insecticide prolonged pupal developmental
      time in the C. externa F1 generation. Thiamethoxam treatment also had a
      transgenerational effect on exposed H. axyridis larvae, reducing pupal survival
      in the F1 generation. In the adult bioassay, thiamethoxam treatment reduced egg
      fertility of C. externa, prolonged the larval period, and reduced both fecundity
      and egg fertility of the F1 generation. Thiamethoxam also caused
      transgenerational effect on H. axyridis adults, reducing larval survival of the
      F1 generation. CONCLUSION: Thiamethoxam seed treatment was harmful for both
      predators, but C. externa was more affected by the insecticide than H. axyridis.
      (c) 2018 Society of Chemical Industry.

PMID- 30094904
TI  - Alkyl Chain Introduction: In Situ Solar-Renewable Colorful Organic
      Mechanoluminescence Materials.
AB  - Mechanoluminescence (ML) materials are environmentally friendly and emit light by
      utilizing mechanical energy. This has been utilized in light sources, displays,
      bioimaging, and advanced sensors. Organic ML materials are strongly limited to
      application by in situ unrepeatable ML. Now, in situ solar-renewable organic ML
      materials can be formed by introducing a soft alkyl chain into an ML unit. For
      the first time, the ML from these polycrystalline thin films can be iteratively
      produced by simply recrystallizing the fractured crystal in situ after a
      contactless exposure to sunlight within a short time (<=60 s). Additionally,
      their ML color and lifetime can be also easily tuned by doping with organic
      luminescent dyes. Therefore, large-area sandwich-type organic ML devices can be
      fabricated, which can be repeatedly used in a colorful piezo-display, visual
      handwriting monitor, and sensitive optical sensor, showing a lowest pressure
      threshold for ML of about 5 kPa.

PMID- 30094905
TI  - The route and rate of thiamethoxam soil degradation in laboratory and outdoor
      incubated tests, and field studies following seed treatments or spray
      application.
AB  - BACKGROUND: The route and rate of degradation of thiamethoxam in the laboratory
      and field was investigated. The effect of dark incubation versus light/dark
      cycles, seed treatment versus spray, and watering-in for spray application was
      explored in side-by-side trials. RESULTS: Geometric mean DT50 values were 75.4
      days in OECD307 studies, and 18.3 (spray) and 16.5 (seed treatment) days in the
      field. In laboratory soil core studies DT50 values were 24.9 to 43.5 days, with
      the lowest value from the light/dark incubated soil core. Mean clothianidin
      formation was 19.7% applied thiamethoxam [mol/mol] in OECD307 studies and 17.5
      (spray) and 3.4% (seed) in field trials. CONCLUSION: Soil DT50 values decreased
      with increasingly realistic tests (laboratory OECD307 to soil cores to soil cores
      with a light/dark cycle to field trials). The majority of the differences were
      associated with the soil treatment in OECD307 studies which destroys soil
      structure and retards the degradation rate; and from the impact on soil pore
      water movement in light/dark conditions. Degradation rates in the field were
      comparable between spray application and seed treatments. Maximum clothianidin
      concentrations were four-fold lower for seed treatments than for spray
      application in field studies. (c) 2018 The Authors. Pest Management Science
      published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

PMID- 30094906
TI  - Rhodium-Catalyzed Regioselective N2 -Alkylation of Benzotriazoles with Diazo
      Compounds/Enynones via a Nonclassical Pathway.
AB  - A novel rhodium-catalyzed highly selective N2 -alkylation of benzotriazoles with
      diazo compounds/enynones is achieved, providing N2 -alkylated benzotriazoles in
      good to excellent yields and with excellent N2 selectivities. Importantly,
      different to traditional carbene insertion into X-H (X=N, O etc) bonds, DFT
      calculations disclose that this selective N2 -alkylation probably proceeds
      through a formal 1,3- rather than 1,2-H shift to give the final products.

PMID- 30094907
TI  - Acquired ornithine transcarbamylase deficiency in pediatric and adolescent
      patients with fibrolamellar hepatocellular carcinoma.
AB  - Ornithine transcarbamylase deficiency (OTCD) disrupts the metabolic pathway
      responsible for converting nitrogenous waste to urea, allowing for excretion.
      When impaired, ammonia levels accumulate in the blood resulting in severe,
      sometimes life-threatening toxicities. Abnormalities of the urea cycle are often
      inherited, though there are some rarer acquired forms. We describe two cases of
      acquired OTCD in pediatric patients with fibrolamellar hepatocellular carcinoma
      (FL-HCC). We detail its presentation and management, explore potential underlying
      pathophysiology, and propose a practice change to optimize care of FL-HCC
      patients.

PMID- 30094908
TI  - Gossypol-induced fitness gain and increased resistance to deltamethrin in beet
      armyworm, Spodoptera exigua (Hubner).
AB  - BACKGROUND: In plant-insect interactions, phytotoxins such as gossypol, exert a
      defensive role on behalf of the plant by interfering with the essential
      metabolic, biochemical and physiological pathways of herbivorous insects. The
      beet armyworm, Spodoptera exigua (Hubner), is a key pest for many important crops
      including a range of vegetables, ornamentals, and cotton. In this study, we
      investigated how resistance to deltamethrin relates to enzyme activity in
      gossypol-pretreated larvae of S. exigua. RESULTS: Following selection with
      deltamethrin insecticides on gossypol-pretreated larvae for 10 generations, the
      Gos-SEL population developed a 113.29-fold resistance. Under the same conditions,
      the Delta-SEL selected population showed a 69.76-fold increase in resistance
      along with corresponding levels of xenobiotic defense enzyme activity. Similarly,
      the fecundity of the Delta-SEL population together with male and female longevity
      were found to be significantly lower when compared with the Gos-SEL population
      and the laboratory susceptible-strain group (SS-Strain). In addition, the
      activities of cytochrome P450s in S. exigua were significantly enhanced when the
      insects were fed on a deltamethrin and gossypol-pretreated diet compared with
      being fed on deltamethrin alone. CONCLUSION: The reproductive capacity of S.
      exigua is significantly reduced in Delta-SEL and Gos-SEL populations compared
      with the control group (SS-Strain). Elevation of the major detoxification enzyme
      cytochrome P450 monooxygenase and esterase might have an important role in
      inducing tolerance to deltamethrin in gossypol-fed S. exigua populations. This
      study enhances our understanding of detoxification enzyme pathways for S. exigua
      gene expression and their role in responses to insecticides and plant secondary
      metabolites. (c) 2018 Society of Chemical Industry.

PMID- 30094909
TI  - Lithium Nitrate Solvation Chemistry in Carbonate Electrolyte Sustains High
      Voltage Lithium Metal Batteries.
AB  - The lithium metal anode is regarded as a promising candidate in next-generation
      energy storage devices. Lithium nitrate (LiNO3 ) is widely applied as an
      effective additive in ether electrolyte to increase the interfacial stability in
      batteries containing lithium metal anodes. However, because of its poor
      solubility LiNO3 is rarely utilized in the high-voltage window provided by
      carbonate electrolyte. Dissolution of LiNO3 in carbonate electrolyte is realized
      through an effective solvation regulation strategy. LiNO3 can be directly
      dissolved in an ethylene carbonate/diethyl carbonate electrolyte mixture by
      adding trace amounts of copper fluoride as a dissolution promoter. LiNO3 protects
      the Li metal anode in a working high-voltage Li metal battery. When a LiNi0.80
      Co0.15 Al0.05 O2 cathode is paired with a Li metal anode, an extraordinary
      capacity retention of 53 % is achieved after 300 cycles (13 % after 200 cycles
      for LiNO3 -free electrolyte) and a very high average Coulombic efficiency above
      99.5 % is achieved at 0.5 C. The solvation chemistry of LiNO3 -containing
      carbonate electrolyte may sustain high-voltage Li metal anodes operating in
      corrosive carbonate electrolytes.

PMID- 30094910
TI  - Factors associated with potentially harmful drug-drug interactions in older
      Korean people: A population-based study.
AB  - AIM: The present study investigated the status of potentially harmful drug-drug
      interactions (PHDI) in older adults, to obtain insight into factors that
      influence the risk of PHDI. METHODS: The present study included Korean people
      aged >=65 years who were prescribed one or more drugs included in the list of
      PHDI under the Beers Criteria 2015 from January to December, 2016 (n = 1 257
      317). PHDI were defined based on the Beers Criteria 2015. Among 10 PHDI, a
      prevalence of >5% was taken to be clinically significant, and the relationships
      between multiple variables and PHDI were examined. RESULTS: The most frequent
      PHDI was corticosteroids and non-steroidal anti-inflammatory drugs (n = 259 499,
      20.64%), followed by a combination of two or more anticholinergic drugs (n = 139
      622, 11.1%), and three or more drugs acting on the central nervous system (n = 86
      023, 6.84%). These three types of PHDI were more frequent in women (OR 1.066
      1.141) and medical aid beneficiaries (OR 1.095-1.510). The risk of PHDI increased
      in proportion to the number of healthcare institutions used by the participants
      and their outpatient visits during the year (OR 1.043-1.079, 1.008-1.010,
      respectively). The risk of PHDI was low when patients took no more than five
      medications in a single prescription (OR 0.017-0.791). CONCLUSIONS: The findings
      of the present study highlight the three most frequent PHDI in Korea according to
      the Beers Criteria 2015. Healthcare providers should take PHDI into account when
      treating female patients, medical aid beneficiaries, patients using multiple
      healthcare institutions, frequent outpatient visitors and patients prescribed
      more than six medications in a single prescription. Geriatr Gerontol Int 2018;
      18: 1378-1382.

PMID- 30094911
TI  - A Bayesian latent variable approach to aggregation of partial and top-ranked
      lists in genomic studies.
AB  - In genomic research, it is becoming increasingly popular to perform meta
      analysis, the practice of combining results from multiple studies that target a
      common essential biological problem. Rank aggregation, a robust meta-analytic
      approach, consolidates such studies at the rank level. There exists extensive
      research on this topic, and various methods have been developed in the past.
      However, these methods have two major limitations when they are applied in the
      genomic context. First, they are mainly designed to work with full lists, whereas
      partial and/or top-ranked lists prevail in genomic studies. Second, the component
      studies are often clustered, and the existing methods fail to utilize such
      information. To address the above concerns, a Bayesian latent variable approach,
      called BiG, is proposed to formally deal with partial and top-ranked lists and
      incorporate the effect of clustering. Various reasonable prior specifications for
      variance parameters in hierarchical models are carefully studied and compared.
      Simulation results demonstrate the superior performance of BiG compared with
      other popular rank aggregation methods under various practical settings. A non
      small-cell lung cancer data example is analyzed for illustration.

PMID- 30094912
TI  - Sparing subcutaneous septa avoids skin necrosis in the treatment of axillary
      bromhidrosis with suction-curettage shaving.
AB  - BACKGROUND: Surgical treatment of axillary bromhidrosis or hyperhidrosis involves
      the removal of apocrine glands. There are several methods to eliminate apocrine
      glands; however, many methods reported significant rates of skin necrosis. To
      avoid this problem while preserving comparable results, we used a modified method
      sparing several subcutaneous septa, which successfully avoided skin necrosis
      completely in our series of 19 consecutive cases. METHODS: This is a prospective
      case series in a single center by a single surgeon. Unlike other series using
      suction-curettage shaver, we preserved some septa. The skin flaps between septa
      were approximately shaved as thin as 2 mm. The patients rated their smell on a 0
      10 numeric rating scale (NRS-11) preoperatively and postoperatively. The results
      were analyzed with Mann-Whitney U test and Wilcoxon signed-rank test. RESULTS: A
      total of 19 consecutive patients were included. The mean degree of preoperative
      and postoperative smell on the NRS-11 scale was 7.200 and 2.825, respectively.
      There was only one patient who developed postoperative ecchymosis. No other
      complications, such as skin necrosis, hematoma, or infection were found.
      CONCLUSIONS: We modified the suction-curettage cartilage shaver to eliminate the
      complications. Our method reveals a satisfying result, and there were no
      significant complications.

PMID- 30094913
TI  - Prevalence and predictors of co-occurring diabetes and hypertension in community
      dwelling older adults.
AB  - AIM: The objectives of the present study were to estimate the prevalence of co
      occurring diabetes and hypertension among older adults, examine predictors of co
      occurring diabetes and hypertension, and ascertain whether predictors varied by
      race. METHODS: A retrospective analysis was carried out using a statewide survey
      of Alabama community-dwelling older adults (n = 1204). Measures of central
      tendency and frequency distributions were used for univariate analysis. Logistic
      regression was used to predict co-occurring diabetes and hypertension. RESULTS:
      The prevalence of co-occurring diabetes and hypertension among older adults was
      17%. African American race (OR 2.28, 95% CI 1.596-3.255), body mass index >=30
      (OR 2.45, 95% CI 1.732-3.463), heart disease (OR 1.93, 95% CI 1.355-2.756) and
      eye disease (OR 1.44, 95% CI 1.018-2.024) were associated positively with co
      occurring diabetes and hypertension. CONCLUSIONS: The prevalence of co-occurring
      diabetes and hypertension among older adults was alarmingly high. The notable
      difference in the likelihood of co-occurring diabetes and hypertension is
      representative of a racial health disparity that largely disfavors African
      American older adults. Findings from the present study highlight a need for
      identification of older adults who have and who are at risk of co-occurring
      diabetes and hypertension in the general population and in clinical settings, and
      the development and implementation of suitable interventions, particularly
      targeting older African American adults. Geriatr Gerontol Int 2018; 18: 1356
      1360.

PMID- 30094914
TI  - Association between dynapenia and decline in higher-level functional capacity in
      older men with diabetes.
AB  - AIM: The present study aimed to investigate an association between dynapenia or
      sarcopenia and higher-level functional capacity in older diabetes patients.
      METHODS: Diabetes outpatients aged >=65 years were prospectively enrolled.
      Dynapenia and sarcopenia were defined by criteria of the Asian Working Group for
      Sarcopenia, and higher-level functional capacity was assessed using the Tokyo
      Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). Multiple
      regression analysis included TMIG-IC scores as the dependent variable and
      dynapenia or sarcopenia as the explanatory variables. RESULTS: The present study
      included 204 patients. The regression coefficient of the relationship between
      dynapenia and covariance-adjusted TMIG-IC in men was -1.26 (95% confidence
      interval -2.35 to -0.17, P = 0.024), and that of sarcopenia and TMIG-CI adjusted
      for covariates was 0.65 (95% confidence interval -1.26 to 2.58, P = 0.500). We
      observed no significant correlation between TMIG-IC scores and dynapenia or
      sarcopenia in women. CONCLUSIONS: A statistically significant association was
      found between dynapenia and decline of higher-level functional capacity in older
      men with diabetes. Geriatr Gerontol Int 2018; 18: 1393-1397.

PMID- 30094916
TI  - How Lactobacillus plantarum shapes its transcriptome in response to contrasting
      habitats.
AB  - Triplets of Lactobacullus plantarum strains were isolated from nine contrasting
      habitats. Without any passage through other culture media, isolation and
      cultivation were on model media that strictly reproduced the chemical and
      physical conditions and stressors of the habitats of origin. Here, we
      demonstrated how L. plantarum regulates and shapes its transcriptome in response
      to contrasting habitats. Firstly, multivariate clustering analysis of
      transcriptional data (RNA-Seq), complemented with metabolomics and phenomics,
      grouped the strains according to the habitats of origin. Subsequently, selected
      strains from each habitat switched to repeated cultivation on MRS medium and
      transcriptomes homogenized into a unique cluster. Adaptation to this common
      medium mainly relied on activation of genes for phage- and prophage-related
      proteins and transposases. Finally, the comparison of growth across model media
      and with respect to MRS medium showed that 44% of the overall 3112 gene
      transcripts changed depending on the specific habitat. Regulation and shaping of
      transcriptomes mainly concerned carbohydrate acquisition, pyruvate catabolism,
      proteolytic system and amino acid, lipid and inorganic ion transport and
      metabolism, with contrasting responses for contrasting habitats. Pathways
      reconstruction demonstrated how the large genome size of L. plantarum imparts
      transcriptome and metabolic flexibility as the basic mechanism for a nomadic
      lifestyle.

PMID- 30094917
TI  - Liposome encapsulation and EDTA formulation of dsRNA targeting essential genes
      increase oral RNAi-caused mortality in the Neotropical stink bug Euschistus
      heros.
AB  - BACKGROUND: The Neotropical stink bug Euschistus heros is a major pest in soybean
      fields. Development of highly species-specific pesticides based on RNA
      interference (RNAi) could provide a new sustainable and environmentally friendly
      control strategy. RESULTS: Here, the potential of RNAi as a pest control tool
      against E. heros was assessed. First, target gene selection using a
      microinjection approach was performed. Seven of the 15 candidate genes tested
      exhibited > 95% mortality after hemolymph injection of 27.5 ng dsRNA.
      Subsequently, dsRNA was administered orally using different formulations: naked
      dsRNA, liposome-encapsulated-dsRNA and dsRNA formulated with EDTA. Liposome
      encapsulated dsRNA targeting vATPase A and muscle actin led to significant
      mortality after 14 days (45% and 42%, respectively), whereas EDTA-formulated
      dsRNA did so for only one of the target genes. Ex vivo analysis of the dsRNA
      stability in collected saliva indicated a strong dsRNA-degrading capacity by E.
      heros saliva, which could explain the need for dsRNA formulations. CONCLUSION:
      The results demonstrate that continuous ingestion of dsRNA with EDTA or liposome
      encapsulated dsRNA can prevent dsRNA from being degraded enzymatically and
      suggest great potential for using these formulations in dsRNA delivery to use
      RNAi as a functional genomics tool or for pest management of stink bugs. (c) 2018
      Society of Chemical Industry.

PMID- 30094915
TI  - A molecular signature for delayed graft function.
AB  - Chronic kidney disease and associated comorbidities (diabetes, cardiovascular
      diseases) manifest with an accelerated ageing phenotype, leading ultimately to
      organ failure and renal replacement therapy. This process can be modulated by
      epigenetic and environmental factors which promote loss of physiological function
      and resilience to stress earlier, linking biological age with adverse outcomes
      post-transplantation including delayed graft function (DGF). The molecular
      features underpinning this have yet to be fully elucidated. We have determined a
      molecular signature for loss of resilience and impaired physiological function,
      via a synchronous genome, transcriptome and proteome snapshot, using human renal
      allografts as a source of healthy tissue as an in vivo model of ageing in humans.
      This comprises 42 specific transcripts, related through IFNgamma signalling,
      which in allografts displaying clinically impaired physiological function (DGF)
      exhibited a greater magnitude of change in transcriptional amplitude and elevated
      expression of noncoding RNAs and pseudogenes, consistent with increased
      allostatic load. This was accompanied by increased DNA methylation within the
      promoter and intragenic regions of the DGF panel in preperfusion allografts with
      immediate graft function. Pathway analysis indicated that an inability to
      sufficiently resolve inflammatory responses was enabled by decreased resilience
      to stress and resulted in impaired physiological function in biologically older
      allografts. Cross-comparison with publically available data sets for renal
      pathologies identified significant transcriptional commonality for over 20 DGF
      transcripts. Our data are clinically relevant and important, as they provide a
      clear molecular signature for the burden of "wear and tear" within the kidney and
      thus age-related physiological capability and resilience.

PMID- 30094918
TI  - Prevalence and outcomes of accidental hypothermia among elderly patients in
      Japan: Data from the J-Point registry.
AB  - AIM: We aimed to evaluate the prevalence and outcomes of accidental hypothermia
      (AH) among elderly patients in Japan. METHODS: This was a multicenter chart
      review study of patients with AH (Japanese accidental hypothermia network
      registry; J-Point registry) that included patients with a body temperature <=35 
      degrees C and those aged >=18 years who visited the emergency department of 12
      institutions in Japan from 1 April 2011 to 31 March 2016. The patients were
      classified into three groups: adult (aged 18-64 years), young-old (aged 65-79
      years) and old-old (aged >=80 years). The association between each age category
      and in-hospital mortality from AH was examined through a multivariable logistic
      regression analysis. RESULTS: In total, 572 patients were registered in the J
      Point registry database, of which 537 were included. The proportion of
      individuals who developed AH in an indoor setting was higher in the old-old group
      than in the adult group (86.9% [226/260] vs 61.1% [87/113]). The in-hospital
      mortality rates of the adult, young-old and old-old groups were 15.0% (17/113),
      21.3% (35/164) and 30.4% (79/260), respectively. In the multivariable analysis,
      the in-hospital mortality rate was higher in the young-old and old-old groups
      than in the adult group (young-old vs adult, adjusted odds ratio: 2.31 and 95%
      confidence interval 1.16-4.64; old-old vs adult, adjusted odds ratio: 2.91 and
      95% confidence interval 1.41-6.02). CONCLUSIONS: Approximately 80% of patients
      with AH were aged >=65 years. The in-hospital mortality rate of patients aged
      >=65 years was significantly higher than that of those aged <65 years. Geriatr
      Gerontol Int 2018; 18: 1427-1432.

PMID- 30094919
TI  - Cold signaling in plants: Insights into mechanisms and regulation.
AB  - To survive under cold temperatures plants must be able to perceive a cold signal
      and transduce it into downstream components that induce appropriate defense
      mechanisms. In addition to inducing adaptive defenses, such as the production of
      osmotic factors to prevent freezing and the reprogramming of transcriptional
      pathways, cold temperatures induce changes in plant growth and development which
      can affect the plant life cycle. In this review, we summarize recent progress in
      characterizing cold-related genes and the pathways that allow transduction of the
      cold signal in plants, focusing primarily on studies in Arabidopsis thaliana and
      rice (Oryza sativa). We summarize cold perception and signal transduction from
      the plasma membrane to the nucleus, which involves cold sensors, calcium signals,
      calcium-binding proteins, mitogen-activated protein kinase cascades, and the C
      repeat binding factor/dehydration-responsive element binding pathways, as well as
      trehalose metabolism. Finally, we describe the balance between plant
      organogenesis and cold tolerance mechanisms in rice. This review encapsulates the
      known cold signaling factors in plants and provides perspectives for ongoing cold
      signaling research.

PMID- 30094920
TI  - The effects of temperature on the development, fecundity and mortality of
      Eretmocerus warrae: is Eretmocerus warrae better adapted to high temperatures
      than Encarsia formosa?
AB  - BACKGROUND: Eretmocerus warrae (Hymenoptera: Aphelinidae) is a parasitoid of the
      glasshouse whitefly, Trialeurodes vaporariorum (Hemiptera: Aleyrodidae). Here, we
      compare its potential as a biological control agent at high temperatures to that
      of Encarsia formosa (Hymenoptera: Aphelinidae), a wasp which is widely sold for
      control of T. vaporariorum. RESULTS: Eretmocerus warrae attained the highest
      estimated developmental rate at 31.4  degrees C and the maximum oviposition rate
      at 30.5  degrees C. Developmental times of E. warrae at fluctuating temperatures
      that simulate night-day patterns were similar to those predicted based on
      constant temperatures. Above the optimum temperature, E. warrae tolerated higher
      constant temperatures than En. formosa during development and as adults. Using a
      ramping temperature approach, the critical thermal maximum for adult E. warrae
      was significantly higher than that of adult En. formosa. CONCLUSION: Eretmocerus
      warrae is better adapted to high temperatures than En. formosa, and could
      therefore be a complementary or superior biological control agent during summer
      months in hot regions. (c) 2018 Society of Chemical Industry.

PMID- 30094921
TI  - Primary cutaneous adenoid cystic carcinoma mimicking dermal cylindroma: histology
      of the complete surgical excision as the key to diagnosis.

PMID- 30094922
TI  - Amphiphilic Carbazole-Containing Compounds with Lower Critical Solution
      Temperature Behavior for Supramolecular Self-Assembly and Solution-Processable
      Resistive Memories.
AB  - The self-organization and resistive memory performances of a series of newly
      synthesized water-soluble amphiphilic carbazole derivatives have been explored.
      Temperature-dependent UV/Vis absorption spectroscopy has been conducted to study
      the isodesmic self-assembly mechanism of the carbazole-containing compounds. This
      class of compounds also exhibits interesting lower critical solution temperature
      properties, which are sensitive to concentration and ionic additives. One of the
      compounds has been solution-processed and utilized as an active material in the
      engineering of resistive memory devices, exhibiting a switching voltage of about
      3.9 V, a constant ON/OFF current ratio of 106 , and a long retention time of 104 
      s. The present work demonstrates the versatile potential applications of water
      soluble amphiphilic carbazole-containing compounds in supramolecular chemistry
      and resistive memory devices.

PMID- 30094923
TI  - Quantitative Analysis of the Global Proteome in Peripheral Blood Mononuclear
      Cells from Patients with New-Onset Psoriasis.
AB  - Psoriasis is a common chronic autoimmune skin disease involving the activation of
      T cells. To explore the proteomic signature of peripheral blood mononuclear
      cells, a quantitative analysis of their global proteome was conducted in samples
      from Chinese patients with new-onset psoriasis (n = 31) and healthy controls (n =
      32) using an integrated quantitative approach with tandem mass tag labeling and
      LC-MS/MS. Protein annotation, unsupervised hierarchical clustering, functional
      classification, functional enrichment and cluster, and protein-protein
      interaction analyses were performed. A total of 5178 proteins were identified, of
      which 4404 proteins were quantified. The fold-change cutoff was set at 1.2
      (patients vs controls); 335 proteins were upregulated, and 107 proteins were
      downregulated. The bioinformatics analysis indicated that the differentially
      expressed proteins were involved in processes related to the activation of immune
      cells including the nuclear factor kappa-light-chain-enhancer of activated B
      cells (NF-kappaB) pathway, cellular energy metabolism, and proliferation. Three
      upregulated proteins and two phosphorylated proteins in the NF-kappaB pathway
      were verified or identified by Western blotting. These results confirm that the
      NF-kappaB pathway is critical to psoriasis. In addition, many differentially
      expressed proteins identified in this study have never before been associated
      with psoriasis, and further studies on these proteins are necessary.

PMID- 30094924
TI  - Gate Tunable Organic Light Emitting Diodes: Principles and Prospects.
AB  - This record summarizes our recent developments on gate-tunable organic light
      emitting diodes (OLEDs). The key point is to modulate the charge carrier
      injection barrier by the applied gate potential. One way is to electrochemically
      dope charge carrier injection layer through porous electrodes. The
      electrochemically doped charge carrier layer thus form gate-tunable contact with
      porous electrodes. Another way is to modulate the work-function of electrodes
      that can have varied charge carrier injection barriers following the applied gate
      potential. Gate-tunable OLEDs based on these two working principles have been
      fabricated, characterized and demonstrated for displaying simple digitals and
      letters. New materials including dielectric, porous electrodes, work function
      tunable electrodes, and charge carrier injection materials have been further
      explored for performance improvement.

PMID- 30094925
TI  - Assembly of Sub-Crystals on the Macroscale and Construction of Composite Building
      Units on the Microscale for SAPO-34.
AB  - The nucleation and growth of SAPO-34 crystals with triethylamine (TEA) as a
      single template was monitored with ex situ time-resolved characterization
      methods. The investigation focused on the evolution of the intermediate phases at
      different crystallization stages of SAPO-34. The morphology transformation of the
      intermediate phases at different crystallization times revealed the unique self
      assembly process of the sub-crystals. The cubic SAPO-34 crystals can be
      constructed from eight pyramidal subunits. Additionally, the construction order
      of cha cages and double-six-membered ring (d6r) units in the initial
      crystallization stage was determined. The appearance of cha cages prior to d6r
      units can be attributed to the structure-directing effect of protonated TEA,
      which is charge balanced with the negative charge of the framework from Si
      incorporation. Further analysis showed that Si species were incorporated into the
      framework by direct participation in the initial crystallization stage and
      substitution for framework P atoms during the later stage.

PMID- 30094926
TI  - The management of childhood cancer survivors at risk for stroke: A Delphi survey
      of regional experts.
AB  - BACKGROUND: Evidence is not available to guide management of childhood cancer
      survivors (CCS) at risk for radiation-associated cerebral vascular disease (CVD)
      and stroke. We propose to use a consensus-based methodology to describe the
      collective opinion of regional experts for the care of these patients and
      identify areas of controversy. PROCEDURE: Thirty physicians from the New England
      region who care for CCS participated in a Delphi panel querying their management
      approach (imaging, laboratory tests, medications, counseling, referrals) to a CCS
      treated with cranial radiation formatted as five clinical scenarios
      (asymptomatic, small- and large-vessel CVD, transient ischemia, stroke) in three
      rounds of anonymous questionnaires. Consensus defined as >=90% agreement.
      RESULTS: Response rate was 100% for all three rounds. Panelists reached consensus
      on laboratory tests to assess stroke risk factors, stroke risk and prevention
      counseling, brain imaging to monitor survivors with known CVD, and acute care for
      stroke symptoms. Only 67% panelists agreed with MRI screening asymptomatic
      survivors with no history of CVD, 87% endorsed aspirin as stroke prevention for
      large-vessel CVD and 57% for small-vessel CVD. There was no consensus on
      specialty referrals. Overall, panelists practicing at large institutions and
      neurology subspecialists were more likely to advocate for screening,
      interventions, and referrals. CONCLUSIONS: Despite lack of evidence to guide
      stroke prevention in CCS treated with cranial radiation, a panel of regional
      physicians reached consensus on managing most clinical scenarios. Controversial
      areas requiring further study are surveillance imaging for asymptomatic
      survivors, aspirin for stroke prevention, and indications for specialty referral.

PMID- 30094927
TI  - Benzoic acid in nursery diets increases the performance from weaning to finishing
      by reducing diarrhoea and improving the intestinal morphology of piglets
      inoculated with Escherichia coli K88.
AB  - A total of 224 weaned pigs (DanBred sows x PIC 337 sires) with an average body
      weight (BW) of 6.37 +/- 0.34 kg (21 days of age) were used to evaluate how
      different levels of benzoic acid fed to weaning pigs orally inoculated with
      Escherichia coli (K88+ ) affected the nursing and grow-finishing performance, the
      physicochemical properties of the intestine, the volatile fatty acid
      concentration in the caecum and the incidence of diarrhoea. Pigs were randomly
      allocated in an experimental design of randomized blocks in a 4 * 2 factorial
      design, and they were administered four levels of benzoic acid (0.00%, 0.25%,
      0.50% and 0.75%) and inoculated (or not) in two consecutive days with 1 ml
      solution containing 106 CFU/ml of E. coli (K88+ ). Seven replicates (pens) per
      treatment were used, and four animals were kept per pen. Supplementation with
      0.75% benzoic acid promoted better performance (p < 0.05) in the nursery phase as
      well as in the subsequent phases until slaughter, and it decreased the incidence
      of diarrhoea in piglets (p < 0.05). In the piglets fed the benzoic acid diet, the
      villus height in the jejunum and ileum was greater until 42 days of life (p <
      0.05), the crypt depth was decreased in the caecum (p < 0.05), and the butyric
      acid concentration was increased in the caecal content tendencially (p = 0.0708).
      In conclusion, supplementation with 0.75% benzoic acid has a positive effect on
      piglets by reducing diarrhoea, improving intestinal health and promoting the
      performance from weaning to finishing. Thus, benzoic acid can be considered a
      potential alternative that can replace growth-promoting antibiotics.

PMID- 30094929
TI  - Substantial recurrence risk after venous thromboembolism provoked by minor risk
      factors.

PMID- 30094930
TI  - Children with HbSbeta0 thalassemia have higher hemoglobin levels and lower
      incidence rate of acute chest syndrome compared to children with HbSS.
AB  - BACKGROUND: Based on the presumed clinical similarity between the two most severe
      sickle cell disease (SCD) genotypes, hemoglobin (Hb) Sbeta0 thalassemia and HbSS,
      randomized controlled trials (RCTs) have included both genotypes. Our group has
      demonstrated that healthcare providers inadequately distinguish the two diagnoses
      through clinical and laboratory parameters. PROCEDURE: In a retrospective cohort
      study utilizing data from the Silent Cerebral Infarct Transfusion trial
      (NCT00072761), we tested the hypothesis that children with genotypic diagnoses of
      HbSbeta0 thalassemia, when compared to HbSS, have significantly different rates
      of SCD comorbidities. Exclusion criteria included those with previous overt
      stroke or treatment with hydroxyurea or regular blood transfusion therapy.
      RESULTS: Among children with HbSbeta0 thalassemia (n = 22) and HbSS (n = 786),
      the mean hemoglobin was higher in children with HbSbeta0 thalassemia (9.2 g/dl)
      compared to HbSS (8.1 g/dl, P < 0.001). In children with HbSbeta0 thalassemia,
      when compared to HbSS, the incidence rate of acute chest syndrome (ACS) was 3.0
      and 14.4 events per 100 patient-years (P = 0.028), and mean transcranial Doppler
      (TCD) velocities were 112.6 and 135.6 cm/sec, respectively (P = 0.026). The
      number of children with HbSbeta0 thalassemia and HbSS with conditional TCD
      velocities were zero (0%) and 26 (4.9%), respectively (P = 1.00), and the number
      with silent cerebral infarcts were five (27.8%) and 209 (30.8%), respectively (P
      = 0.78). CONCLUSIONS: We have provided preliminary evidence that clinically
      relevant differences occur in ACS rates and TCD velocities between children with
      HbSbeta0 thalassemia and HbSS. Future SCD RCTs should consider balanced
      allocation of these SCD genotypes, particularly when ACS and abnormal TCD
      velocities are primary outcome measures.

PMID- 30094931
TI  - Adenoidzystisches Karzinom der Kopfhaut imitiert dermales Zylindrom: Histologie
      der Gesamtexzision als Schlussel zur Diagnose.

PMID- 30094928
TI  - Baseline characteristics and outcomes of children with cancer in the English
      speaking Caribbean: A multinational retrospective cohort.
AB  - BACKGROUND: English-speaking Caribbean (ESC) childhood cancer outcomes are
      unknown. PROCEDURE: Through the SickKids-Caribbean Initiative (SCI), we
      established a multicenter childhood cancer database across seven centers in six
      ESC countries. Data managers entered patient demographics, disease, treatment,
      and outcome data. Data collection commenced in 2013, with retrospective
      collection to 2011 and subsequent prospective collection. RESULTS: A total of 367
      children were diagnosed between 2011 and 2015 with a median age of 5.7 years
      (interquartile range 2.9-10.6 years). One hundred thirty (35.4%) patients were
      diagnosed with leukemia, 30 (8.2%) with lymphoma, and 149 (40.6%) with solid
      tumors. A relative paucity of children with brain tumors was seen (N = 58,
      15.8%). Two-year event-free survival (EFS) for the cohort was 48.5% +/- 3.2%; 2
      year overall survival (OS) was 55.1% +/- 3.1%. Children with acute lymphoblastic
      leukemia (ALL) and Wilms tumor (WT) experienced better 2-year EFS (62.1% +/- 6.4%
      and 66.7% +/- 10.1%), while dismal outcomes were seen in children with acute
      myeloid leukemia (AML; 22.7 +/- 9.6%), rhabdomyosarcoma (21.0% +/- 17.0%), and
      medulloblastoma (21.4% +/- 17.8%). Of 108 deaths with known cause, 58 (53.7%)
      were attributed to disease and 50 (46.3%) to treatment complications. Death
      within 60 days of diagnosis was relatively common in acute leukemia [13/98
      (13.3%) ALL, 8/26 (30.8%) AML]. Despite this, traditional prognosticators
      adversely impacted outcome in ALL, including higher age, higher white blood cell
      count, and T-cell lineage. CONCLUSIONS: ESC childhood cancer outcomes are
      significantly inferior to high-income country outcomes. Based on these data,
      interventions for improving supportive care and modifying treatment protocols are
      under way. Continued data collection will allow evaluation of interventions and
      ensure maximal outcome improvements.

PMID- 30094932
TI  - Multiple bloodstream infections in pediatric stem cell transplant recipients: A
      case series.
AB  - Bacterial bloodstream infections (BSIs) are associated with poor outcomes
      following stem cell transplantation (SCT). We describe the demographics,
      treatment, complications, and outcome of 23 pediatric SCT recipients who
      developed three or more BSIs in the first year after SCT at our center from 2011
      through 2016. The majority underwent allogeneic SCT (n = 22/23;96%), mainly from
      an unrelated donor (n = 19/22,86%); developed grade 2-4 graft versus host disease
      (GVHD; n = 14/23, 61%), all steroid refractory; and were diagnosed with
      thrombotic microangiopathy (n = 21/23, 91%). One-year overall survival was 56% (n
      = 13/23). We observed a high rate of transplant-associated thrombotic
      microangiopathy and steroid-refractory acute GVHD in patients with three or more
      BSIs.

PMID- 30094935
TI  - A new UROD mutation in childhood porphyria cutanea tarda after allogeneic stem
      cell transplantation for beta-thalassemia major.

PMID- 30094933
TI  - Honey bee neurogenomic responses to affiliative and agonistic social
      interactions.
AB  - Social interactions can be divided into two categories, affiliative and
      agonistic. How neurogenomic responses reflect these opposing valences is a
      central question in the biological embedding of experience. To address this
      question, we exposed honey bees to a queen larva, which evokes nursing, an
      affiliative alloparenting interaction, and measured the transcriptomic response
      of the mushroom body brain region at different times after exposure. Hundreds of
      genes were differentially expressed at distinct time points, revealing a dynamic
      temporal patterning of the response. Comparing these results to our previously
      published research on agonistic aggressive interactions, we found both shared and
      unique transcriptomic responses to each interaction. The commonly responding gene
      set was enriched for nuclear receptor signaling, the set specific to nursing was
      enriched for olfaction and neuron differentiation, and the set enriched for
      aggression was enriched for cytoskeleton, metabolism, and chromosome
      organization. Whole brain histone profiling after the affiliative interaction
      revealed few changes in chromatin accessibility, suggesting that the
      transcriptomic changes derive from already accessible areas of the genome.
      Although only one stimulus of each type was studied, we suggest that elements of
      the observed transcriptomic responses reflect molecular encoding of stimulus
      valence, thus priming individuals for future encounters. This hypothesis is
      supported by behavioral analyses showing that bees responding to either the
      affiliative or agonistic stimulus exhibited a higher probability of repeating the
      same behavior but a lower probability of performing the opposite behavior. These
      findings add to our understanding of the biological embedding at the molecular
      level.

PMID- 30094934
TI  - Association between high-sensitivity C-reactive protein, lipoprotein-associated
      phospholipase A2 and carotid atherosclerosis: A cross-sectional study.
AB  - High-sensitivity C-reactive protein (hs-CRP) and lipoprotein-associated
      phospholipase A2 (Lp-PLA2) have been reported to be independent predictors of
      atherosclerosis. However, whether the combination of these two markers can
      improve the prediction of atherosclerosis is unknown. This study aimed to
      evaluate the association between combining hs-CRP and Lp-PLA2 and predicting
      carotid atherosclerosis. A total of 1982 participants aged >=40 years were
      included in this study. Hs-CRP and Lp-PLA2 were measured by a high-sensitivity
      nephelometry assay and quantitative sandwich enzyme-linked immunosorbent assay,
      respectively. Ultrasonography was performed on the bilateral carotid arteries to
      evaluate stenosis and plaques. Multivariable logistic regression models were used
      to analyse the association between the combination of the hs-CRP and Lp-PLA2
      levels and carotid plaques and stenosis. A total of 1579 (79.7%) and 181 (9.1%)
      subjects had carotid plaques and carotid stenosis, respectively. The group with
      high hs-CRP and Lp-PLA2 levels had the highest prevalence of carotid plaques
      (90.6%) and stenosis (20.8%). A significant association was found between high hs
      CRP and Lp-PLA2 levels and carotid stenosis (adjusted odds ratio [OR]: 2.39; 95%
      confidence interval [CI]: 1.13-5.09), but this combination was not associated
      with carotid plaques (OR: 2.62, 95% CI: 0.93-7.38). The results suggested that
      the combination of hs-CRP and Lp-PLA2 were better predictors than either protein
      alone with regard to carotid atherosclerosis.

PMID- 30094936
TI  - A novel mutation in CYBB gene in a patient with chronic colitis and recurrent
      pneumonia due to X-linked chronic granulomatous disease.

PMID- 30094938
TI  - Micellar enhanced spectrofluorimetric approach for nanogram detection of certain
      alpha1 -blocker drugs: Application in pharmaceutical preparations and human
      plasma.
AB  - Alpha1-adrenergic-blocking drugs, namely; alfuzosin hydrochloride (ALF),
      doxazosin mesylate (DOX) and terazosin hydrochloride (TER) are effective as
      antihypertensive agents as well as in management of benign prostatic hypertrophy.
      In this study, a simple, very fast, highly sensitive and cheap technique was
      optimized for assay of these drugs in pure states and pharmaceutical tablets. The
      proposed method is dependent on enhancement of the native fluorescence of
      investigated drugs using the polyoxyethylene 50 stearate (POE50S) micellar
      system. The method showed excitation at 325, 340 and 250 nm for ALF, DOX and TER,
      respectively and an emission maxima at 382 nm. The fluorescence intensity
      concentration charts of studied drugs were attained utilizing concentration
      ranges (2.0-60.0 ng mL-1 ) for DOX and (4.0-100.0 ng mL-1 ) for ALF and TER with
      quantitation limits 2.9, 1.6 and 2.5 ng mL-1 for ALF, DOX and TER, respectively.
      The suggested technique was approved according to International Council for
      Harmonisation (ICH) standards and the United States Food and Drug Administration
      (US FDA) bioanalytical method validation and has been effectively applied for
      assay of these medications in their dosage forms as well as for content
      uniformity test. The developed procedure was also efficiently applied for
      determination of these drugs in real human plasma with high accuracy.

PMID- 30094937
TI  - Assessment of physical function in children with cancer: A systematic review.
AB  - BACKGROUND: Appropriate selection of robust assessment tools is essential to
      monitor physical function in children with cancer during and after treatment.
      This systematic review aims to identify and critically appraise the measurement
      properties of physical function measures currently used for children with cancer.
      PROCEDURE: Two systematic searches of seven electronic databases [Cumulative
      Index to Nursing and Allied Health Literature (CINHAL), Medline, PubMed,
      PsychINFO, Sportsdiscus, EMBASE, and Allied and Complementary Medicine Database
      (AMED)] were completed to identify physical function measures used in children
      with cancer and to evaluate their measurement properties. Methodological quality
      and the adequacy of measurement properties specific to populations of children
      with cancer were critically appraised using the COSMIN framework to ascertain
      which measures have evidence to support their use in children with cancer.
      RESULTS: One hundred and one physical function measures were identified across
      154 studies. Measurement property data were available for 12 measures. The
      measurement properties of only two outcome measures were assessed in more than
      one study. Despite some positive measurement property data, there was no
      assessment tool that had consistent and adequate evidence overall to recommend
      its use in childhood cancer populations. Poor methodological quality of the
      included studies was the main limiting factor. CONCLUSIONS: There is very limited
      population specific evidence to guide the selection of physical function measures
      in children with cancer. Further research into the reliability, validity and
      responsiveness of physical function measures in children with cancer is needed to
      provide a basis for more effective clinical assessment and management.

PMID- 30094939
TI  - Three-dimensional laparoscopy-assisted bowel resection for cavernous hemangioma
      of the rectum: Report of two cases.
AB  - The safety and feasibility of 3-D laparoscopy-assisted bowel resection were
      demonstrated in the management of rectal cancer. However, this procedure's role
      in the management of patients with diffuse cavernous hemangioma of the rectum has
      not been evaluated. Here, two patients were diagnosed with diffuse cavernous
      hemangioma of the rectum by colonoscopy and abdominal imaging. One case underwent
      pull-through transection and coloanal anastomosis in 3-D laparoscopy-assisted
      surgery. In another patient, 3-D laparoscopy-assisted abdominoperineal resection
      was performed. The operations were safely performed in both cases. The two
      patients recovered uneventfully, and satisfactory postoperative outcomes were
      demonstrated. This report shows that 3-D laparoscopy-assisted bowel resection may
      be safe and feasible for patients with diffuse cavernous hemangioma of the
      rectum.

PMID- 30094940
TI  - Microproteomic Profiling of High-Grade Squamous Intraepithelial Lesion of the
      Cervix: Insight into Biological Mechanisms of Dysplasia and New Potential
      Diagnostic Markers.
AB  - PURPOSE: High-grade squamous intraepithelial lesion (HSIL) is a known precursor
      for squamous cell carcinoma of uterine cervix. Although it is known that SILs are
      associated to infection by human papillomavirus, downstream biological mechanisms
      are still poorly described. In this study, we compared the microproteomic profile
      of HSIL to normal tissues: ectocervix (ectoC) and endocervix (endoC).
      EXPERIMENTAL DESIGN: Tissue regions of endoC, ectoC, and HSlL were collected by
      laser microdissection (3500 cells each) from five patients. Samples were
      processed and analyzed using our recently developed laser microdissection-based
      microproteomic method. Tissues were compared in order to retrieve HSIL's
      proteomic profile. Potentially interesting proteins for pathology were stained by
      immunohistochemistry. RESULTS: We identified 3072 proteins among the fifteen
      samples and 2386 were quantified in at least four out of the five biological
      replicates of at least one tissue type. We found 236 proteins more abundant in
      HSIL. Gene ontology enrichments revealed mechanisms of DNA replication and RNA
      splicing. Despite the squamous nature of HSIL, a common signature between HSIL
      and endoC could be found. Finally, potential new markers could support diagnosis
      of dysplasia in SILs. CONCLUSION AND CLINICAL RELEVANCE: This microproteomic
      investigation of HSIL gives insights into the biology of cervical precancerous
      lesions.

PMID- 30094941
TI  - Rheumatoid Arthritis of Knee Joints: MRI-Pathological Correlation.
AB  - OBJECTIVE: To evaluate the correlation between features of knee joint rheumatoid
      arthritis (RA) identified on MRI and histological examination as a means of
      elucidating the pathogenesis of joint destruction in RA. METHODS: This is a
      prospective analysis of 26 knee joints of 22 patients who underwent total knee
      arthroplasty (TKA) for the treatment of RA. Based on the degree of destruction of
      articular cartilage and the menisci, the occurrence of bone marrow edema and bone
      erosion, and synovial thickening, the stage of the knee joints were classified
      using MRI by two radiologists. Differences in the severity of destruction of the
      articular cartilage of the medial and lateral femoral condyles and medial and
      lateral tibial plateaus, the medial and lateral menisci, and bone were compared
      using analysis of variance with a post-hoc test, and the Mann-Whitney U-test.
      Samples of cartilage, subchondral bone, menisci, and synovium were obtained from
      the resected knee specimens during TKA and analyzed semiquantitatively using
      microscopy and immunohistochemistry. Histological differences between areas of
      bone erosion and bone marrow edema were evaluated using a Mann-Whitney U-test.
      RESULTS: The extent of articular destruction was classified as grade 4 for the
      medial and lateral femoral condyles and the medial and lateral tibial plateaus
      for most patients, with an average destruction grade of 3.6 (F = 5.455, P =
      0.002), with the least amount of destruction identified on the lateral femoral
      condyle. The majority of knee joints in the RA patients were at stage 3 (21/26,
      80.8%), followed by stage 4 (4/26, 15.4%). Fibrosis, thinning and destruction,
      and hyperplasia were the most severe pathological changes in cartilage. In a
      total of 26 specimens, 36 areas of bone marrow edema and 68 areas of bone erosion
      were identified, with fibrosis, a mosaic structure of bone, and lymphocyte
      infiltration being the most severe changes in these areas. The degree of meniscus
      destruction was classified as grade 4 in the majority patients for both the
      medial and lateral meniscus, with an average degree of meniscal destruction over
      all specimens of 3.85, and greater destruction of the medial meniscus than of the
      lateral meniscus (Z = 2.062, P = 0.039). Fibrosis and engulfing calcified debris
      were the most severe pathological manifestations. Synovitis was also identified
      in all 26 specimens, with hyperplasia of intima cells and lymphocyte and plasma
      cell infiltration being the most severe pathological manifestations. CONCLUSIONS:
      Severe destruction of the articular cartilage and menisci is a characteristic
      feature of RA. Bone marrow edema and bone erosion can both also be found, but are
      less characteristic. Synovial infiltration may be the triggering mechanism of the
      destruction of the cartilage, menisci, and bone marrow. However, the origin of
      bone marrow edema requires further investigation.

PMID- 30094943
TI  - Meeting public health needs in emergencies-World Health Organization guidelines.
AB  - The World Health Organization (WHO) is a leading source of trustworthy guidelines
      in public health, including in emergencies. In addition to standard guidelines
      produced in preparation for emergency response, WHO has processes and methods for
      issuing guidelines in the context of urgent public health need, including rapid
      advice guidelines (production time 2 to 3 months) and health emergency interim
      guidelines (days to weeks). There are numerous challenges to producing guidelines
      in response to an emergency in addition to the compressed timeline which
      necessitates truncating or modifying standard processes. There is frequently a
      lack of scientific data on the disease or situation at hand, especially early in
      the event timeline. Resources are limited, particularly the availability of WHO
      staff and external experts, and disease and emergency response experts may lack
      knowledge and experience in developing guidelines. Finally, the rapid production
      of new information and the resultant short shelf-life of recommendations pose a
      significant challenge to keeping guidelines up to date. In order to better meet
      end-users' needs, WHO must anticipate areas of uncertainty in emergency response
      and proactively develop relevant guidelines, explore optimal ways of
      communicating gaps in knowledge in the field to guideline developers, and promote
      and participate in research on the sources of bias in guideline development
      within compressed timeframes.

PMID- 30094942
TI  - 'I think we've had a health screen': New offshore screening, new refugee health
      guidelines, new Syrian and Iraqi cohorts: Recommendations, reality, results and
      review.
AB  - AIM: To examine refugee health assessments in Syrian and Iraqi children in the
      context of changes to offshore immigration screening, updated Australian refugee
      health guidelines and the primary care refugee health model in Victoria. METHODS:
      This is a retrospective audit of Syrian and Iraqi children aged 0-17 years
      attending a specialist immigrant health service from January 2015 to September
      2017. RESULTS: We saw 128 children (7 months-16 years, 64.8% male). Prior to
      arrival, 58.9% of children had experienced trauma, and 67.9% had missed at least
      1 year of school. Almost all children (93.3%) were linked with a regular general
      practitioner in Australia, and 23.6% children were linked with a refugee health
      nurse; offshore health records were infrequently available. Of school-aged
      children, 25% were not enrolled in school 3 months after arrival. Only 2 of 113
      (1.8%) children had completed a recommended refugee health assessment, and 55.1%
      had commenced appropriate catch-up vaccination in primary care. After screening
      completion, the most prevalent conditions were low vitamin D (63.6%);
      growth/nutrition (24.2%), neurological/metabolic (16.4%), learning/behaviour
      (15.6%) and mental health (12.5%) concerns; latent tuberculosis infection
      (11.8%); and developmental delay (10.2%). Sixteen children required surgery after
      arrival, and six children had life-threatening medical conditions on arrival -
      only one had an offshore critical alert; care for the other five children
      resulted in 133 unanticipated hospital admission days. CONCLUSIONS: There are
      substantial challenges with the current primary care screening model in Victoria.
      Disability, developmental and mental health concerns were prominent in this
      cohort, and many children had delays in education access, compounding prior
      disadvantage.

PMID- 30094944
TI  - Ramadan fasting alters sleep behavior in type 2 diabetes patients.

PMID- 30094945
TI  - Prevalence of functional GI disorders among pediatric patients with persistent
      asthma.
AB  - OBJECTIVE: Functional gastrointestinal (GI) disorders (FGIDs), such as irritable
      bowel syndrome, functional abdominal pain and dyspepsia, are common causes of
      chronic GI symptoms in children. Prior studies found high comorbidity of FGID and
      asthma. This study aimed to assess the prevalence and comorbidities of FGID among
      pediatric patients with asthma at a university-affiliated urban community
      hospital. METHODS: This prospective, cross-sectional study assessed FGID
      prevalence, asthma control and symptoms of anxiety among pediatric patients with
      persistent asthma. The pediatric ROME III questionnaire was used to assess FGID.
      The Asthma Control Test assessed asthma control. The Beck Anxiety Inventory
      assessed symptoms of anxiety. RESULTS: Of the 110 enrolled patients, 18 (16.4%)
      met the diagnostic criteria for FGID, of which 10 were consistent with the
      diagnosis of functional abdominal pain disorder. Patients with FGID had a
      significantly lower mean asthma control score than patients without FGID (11.5 +/
      4.9 vs 14.8 +/- 5.3, P = 0.03; Cohen's d = 0.6) and higher mean anxiety scores
      than those without FGID (P < 0.01). Asthma control predicted the presence of FGID
      (OR 0.90, 95% CI 0.80-0.99, P = 0.03). However, after adjusted for anxiety,
      asthma control no longer predicted FGID presence (adjusted OR 0.90, 95% CI 0.83
      1.05, P = 0.23). CONCLUSIONS: This study suggests a high prevalence of FGID among
      patients with persistent asthma. Moreover, patients with FGID had poor asthma
      control and increased anxiety. Clinicians should consider FGID in patients with
      poor asthma control and assess them for anxiety.

PMID- 30094946
TI  - Porcine Epidemic Diarrhoea Virus in Italy: Disease spread and the role of
      transportation.
AB  - Porcine Epidemic Diarrhoea Virus (PEDV) causes watery diarrhoea, dehydration, and
      a high mortality rate among suckling pigs. Recently, PEDV had a large negative
      economic impact on the swine industries in Asia and North America. In 2014, PEDV
      re-emerged in many European countries, but most countries only reported a few
      sporadic cases. Here, we report the epidemic wave that occurred in Italy from
      2015 to 2017. During this time, PEDV was detected by real-time PCR in 438 farms
      located mainly in the high-density pig production area in Northern Italy. Most of
      the outbreaks were in farrow-to-finish, farrow-to-wean and finisher farms.
      Clinical signs were observed mainly in suckling and fattening animals, while
      mortality rates were higher in piglets, reaching 50%. A sequence analysis showed
      that a PEDV strain, similar to the OH851 S-INDEL strain isolated in the USA in
      January 2014, was responsible for the outbreaks in Italy in 2015 and 2016.
      However, from January 2017, a recombinant variant strain, containing a portion of
      the Swine Enteric Coronavirus in the S1 gene, spread and almost completely
      outcompeted the previous nonrecombinant strain. In total, 14.1% of the
      environmental swabs collected from trucks at slaughterhouses after animals were
      unloaded tested positive for PEDV before the trucks were cleaned and disinfected,
      and 46% remained positive after cleaning and disinfection processes were
      performed. Moreover, environmental swabs indicated that 17.3% of the empty trucks
      arriving at the farms to load animals were PEDV-positive. This study indicates
      that trucks can have an important role in the spread of PEDV in Italy.

PMID- 30094947
TI  - Multiplanar reconstruction technique for difficult computed tomography-guided
      lung biopsy: Improved accuracy and safety.
AB  - We assessed the value of the multiplanar reconstruction technique (MRT) for
      computed tomography-guided lung biopsy. We evaluated 72 difficult biopsy cases
      (traditional method = 44; MRT = 28) to compare patient and lesion
      characteristics, diagnostic accuracy, complications, radiation dose, and
      procedure duration. Diagnostic accuracy was significantly higher using MRT than
      the traditional method (100% vs. 84.1%, respectively; P = 0.038). There were no
      severe complications in the MRT group, but one case each of severe pneumothorax
      and fatal hemothorax in the traditional method group. The dose-length product
      rate was lower and the procedure duration slightly higher in the MRT than in the
      traditional group (336.83 vs. 479.64 and 33.39 vs. 25.93 minutes, respectively).
      MRT using computed tomography-guided lung biopsy could improve diagnostic
      accuracy and avoid severe complications compared to the traditional method.

PMID- 30094948
TI  - Effects of depression on heart rate variability in elderly patients with stable
      coronary artery disease.
AB  - BACKGROUND: Depression is an independent risk factor in coronary artery disease
      (CAD). Our objective was to evaluate the impact of depression on heart rate
      variability (HRV) in patients with stable CAD. METHODS: This study included
      patients with a stable CAD who admitted to our hospital in the geriatric medical
      center from August 2016 to December 2016. All patients agreed to participate in
      the study and sign informed consent. The study group included 90 CAD patients
      with a diagnosis of depression and 99 CAD patients without depression. All study
      population underwent a 24-hour Holter recording for HRV. The depression was
      assessed by 5-Item Geriatric Depression. RESULTS: There was a linear correlation
      between age and HRV. There were no significant differences in heart rate
      variability between male and female patients, married and unmarried/widowed,
      smoking and nonsmoking, drinking and nondrinking groups. Multiple linear
      regression analysis showed that there were correlations between depression and
      HRV. beta-blockers were associated with SDNN, SDANN, SDNN index, and RMSSD in
      HRV. CONCLUSION: Depression is an important risk factor for heart rate
      variability in elderly patients with CAD. Clinicians should pay attention for
      evaluation of depressive patients with CAD.

PMID- 30094950
TI  - Glycopeptides as a Tool for Early Detection of Cancer.
AB  - Protein glycosylation, as one of the most common and complex posttranslational
      modifications, plays an important role in many biological processes. Along with
      the intensive progress in MS techniques and development of glycan search tools
      and databases, glycoproteomics has become a popular subject of studies. The
      possibility of simultaneous identification of amino acid sequence, glycosylation
      sites, and glycan composition enabled the monitoring of changes in glycosylation
      patterns in various pathological states. In this issue, Saraswat et al. describe
      MS-based investigations of glycopeptide changes in oral cavity squamous cell
      carcinoma (OSCC). Their findings indicate glycopeptides with changed expression
      levels and the presence of altered glycan forms observed in four proteins derived
      from OSCC patients' sera. Proteins carrying this distinctive pattern are in the
      group of the most abundant components of serum, IgG1, IgG4, HPT, and TRFE, which
      makes their identification more accessible. Described changes, characteristic for
      cancer serum samples, may be considered as potential diagnostic indicators of
      OSCC; however, there is still a need to establish a universal glycopeptide-based
      biomarkers database, where all glycoproteomic data can be collected from all
      types of cancer studies and evaluated using meta-analyses. Only then, early
      diagnosis of patients using MS-based approach will make sense, as those
      investigations are very convoluted, and all efforts made during sample
      preparation and analysis will pay off when comprehensive anticancer prevention
      will be achieved during single measurement.

PMID- 30094949
TI  - High-Performance Magnetic Refrigerant Featuring One-Dimensional Gd-O Chains and O
      Gd3 Triangles.
AB  - Magnetic cooling at low temperature has attracted intensive interest in
      cryogenics research, which may become important as cooling medium for long-wave
      photon detectors to support space exploration. Here, we report a Gd-based
      quaternary magnetic refrigerant material, Gd5 BSi2 O13 , containing chains of
      face-shared GdO9 polyhedra and geometrically frustrated OGd3 triangles. Magnetic
      measurements indicate that Gd5 BSi2 O13 exhibits a large magnetocaloric effect
      (MCE) about 1.74 times that of the practical magnetic refrigerant GGG (-DeltaSm
      =67.0 J kg-1  K-1 ). We analyzed the origin of the large MCE by comparing GdIII 
      containing compounds with different structures and concentrations of GdIII .

PMID- 30094951
TI  - Molecular Recognition of a Thomsen-Friedenreich Antigen Mimetic Targeting Human
      Galectin-3.
AB  - Overexpression of the Thomsen-Friedenreich (TF) antigen in cell membrane proteins
      occurs in 90 % of adenocarcinomas. Additionally, the binding of the TF antigen to
      human galectin-3 (Gal-3), also frequently overexpressed in malignancy, promotes
      cancer progression and metastasis. In this context, structures that interfere
      with this specific interaction have the potential to prevent cancer metastasis. A
      multidisciplinary approach combining the optimized synthesis of a TF antigen
      mimetic with NMR, X-ray crystallography methods, and isothermal titration
      calorimetry assays was used to unravel the molecular structural details that
      govern the Gal-3/TF mimetic interaction. The TF mimetic has a binding affinity
      for Gal-3 similar to that of the TF natural antigen and retains the binding
      epitope and bioactive conformation observed for the native antigen. Furthermore,
      from a thermodynamic perspective, a decrease in the enthalpic contribution was
      observed for the Gal-3/TF mimetic complex; however, this behavior is compensated
      by a favorable gain in entropy. From a structural perspective, these results
      establish our TF mimetic as a scaffold to design multivalent solutions to
      potentially interfere with Gal-3 aberrant interactions and for likely use in
      hampering Gal-3-mediated cancer cell adhesion and metastasis.

PMID- 30094953
TI  - Coral microbiome database: Integration of sequences reveals high diversity and
      relatedness of coral-associated microbes.
AB  - Coral-associated microorganisms are thought to play a fundamental role in the
      health and ecology of corals, but understanding of specific coral-microbial
      interactions are lacking. In order to create a framework to examine coral
      microbial specificity, we integrated and phylogenetically compared 21,100 SSU
      rRNA gene Sanger-produced sequences from bacteria and archaea associated with
      corals from previous studies, and accompanying host, location and publication
      metadata, to produce the Coral Microbiome Database. From this database, we
      identified 39 described and candidate phyla of Bacteria and two Archaea phyla
      associated with corals, demonstrating that corals are one of the most
      phylogenetically diverse animal microbiomes. Secondly, this new phylogenetic
      resource shows that certain microorganisms are indeed specific to corals,
      including evolutionary distinct hosts. Specifically, we identified 2-37 putative
      monophyletic, coral-specific sequence clusters within bacterial genera associated
      with the greatest number of coral species (Vibrio, Endozoicomonas and Ruegeria)
      as well as functionally relevant microbial taxa ("Candidatus Amoebophilus",
      "Candidatus Nitrosopumilus" and under recognized cyanobacteria). This
      phylogenetic resource provides a framework for more targeted studies of corals
      and their specific microbial associates, which is timely given the escalated need
      to understand the role of the coral microbiome and its adaptability to changing
      ocean and reef conditions.

PMID- 30094952
TI  - HIV viral suppression and longevity among a cohort of children initiating
      antiretroviral therapy in Eastern Cape, South Africa.
AB  - INTRODUCTION: There are limited data on viral suppression (VS) in children with
      HIV receiving antiretroviral therapy (ART) in routine care in low-resource
      settings. We examined VS in a cohort of children initiating ART in routine HIV
      care in Eastern Cape Province, South Africa. METHODS: The Pediatric Enhanced
      Surveillance Study enrolled HIV-infected ART eligibility children zero to twelve
      years at five health facilities from 2012 to 2014. All children received routine
      HIV care and treatment services and attended quarterly study visits for up to 24
      months. Time to VS among those starting treatment was measured from ART start
      date to first viral load (VL) result <1000 and VL <50 copies/mL using competing
      risk estimators (death as competing risk). Multivariable sub-distributional
      hazards models examined characteristics associated with VS and VL rebound
      following suppression among those with a VL >30 days after the VS date. RESULTS:
      Of 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12
      months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At
      study enrolment, median weight-for-age z-score (WAZ) was -1.7 (interquartile
      range (IQR):-3.1 to -0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative
      incidence of VS <1000 copies/mL at six, twelve and twenty-four months was 57.6%
      (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to
      87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to
      69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to
      56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95%
      CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable
      models, children with VL >1 million copies/mL at ART initiation were half as
      likely to achieve VS <50 copies/mL (adjusted sub-distributional hazards 0.50; 95%
      CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50
      to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months
      had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative
      risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.
      CONCLUSIONS: We found suboptimal VS among South African children initiating
      treatment and high proportions experiencing VL rebound, particularly among
      younger children. Greater efforts are needed to ensure that all children achieve
      optimal outcomes.

PMID- 30094955
TI  - Clinician attitudes towards borderline personality disorder: A 15-year
      comparison.
AB  - Stigma towards people with borderline personality disorder has been a common
      theme reported within mental health services staff. A longitudinal, mixed method
      design investigated attitudes of mental health staff working at the same public
      health service in 2000 and 2015. Participants from both the 2000 and 2015 samples
      completed a short 10-item version of the Attitude to Personality Disorders
      Questionnaire and identical qualitative questions. The 2015 sample also completed
      the Attitude to Deliberate Self-Harm Questionnaire and the Attitude and Skills
      Questionnaire. Qualitatively, the 2000 sample endorsed much more negative
      descriptions (e.g. 'attention seeking' and 'manipulative'), and the 2015 sample
      focused more on treatment approaches and skills (e.g. 'management plan' and
      'empathy'). Quantitatively, the 2015 sample endorsed more positive attitudes than
      the 2000 sample. This positive attitudinal shift is an encouraging step in
      successful treatment of borderline personality disorder and may reflect a
      changing landscape of the mental health system and greater awareness and use of
      effective treatments. (c) 2018 John Wiley & Sons, Ltd.

PMID- 30094954
TI  - Proteome Profiles of Head Kidney and Spleen of Rainbow Trout (Oncorhynchus
      Mykiss).
AB  - The head kidney and spleen are major lymphoid organs of the teleost fish. The
      authors identify proteome profiles of head kidney and spleen of rainbow trout
      (Oncorhynchus mykiss) using a shotgun proteomic approach. Gene ontology
      annotation of proteins is predicted using bioinformatic tools. This study
      represents detailed proteome profiles of head kidney and spleen of rainbow trout,
      with a total of 3241 and 2542 proteins identified, respectively. It is found that
      lymphoid organs are equipped with a variety of functional proteins related to
      defense, receptor, signal transduction, antioxidant, cytoskeleton, transport,
      binding, and metabolic processes. The identified proteome profiles will serve as
      a template for understanding lymphoid organ functions in salmonids and will
      increase the amount of spectra information of rainbow trout proteins in the
      public data repository PRIDE. This data can be accessed via ProteomeXchange with
      identifiers PXD008473 and PXD008478.

PMID- 30094956
TI  - Sperm cryopreservation of transgender individuals: trends and findings in the
      past decade.
AB  - OBJECTIVES: Awareness and acceptance of transgenderism have increased in the last
      two decades. There is limited literature regarding the incidence and semen
      characteristics of transwomen banking spermatozoa. We sought to assess the
      incidence of sperm cryopreservation of transgender individuals compared with the
      cisgender population in the last 10 years. Semen parameters were also compared
      between the two groups. MATERIALS AND METHODS: We performed a retrospective
      analysis of sperm cryopreservation performed at a single center from 2006 through
      2016. Using available data on indications for banking and prior hormonal therapy
      status, we isolated healthy transgender and cisgender cohorts for semen parameter
      comparison. Linear regression was used to compare the incidence trends. Semen
      parameters were compared using the generalized estimating equations method. The
      rates of semen parameter abnormality of each group were compared using chi-square
      test. Semen parameter abnormalities were defined using WHO 2010 reference values.
      RESULTS: We analyzed 194 transgender samples and 2327 cisgender samples for a
      total of 84 unique transgender sperm bankers and 1398 unique cisgender sperm
      bankers. The number of transgender sperm bankers increased relative to cisgender
      sperm bankers from 2006 to 2016. Following exclusion of cisgender sperm bankers
      with health issues that might impact semen quality and transgender sperm bankers
      with known prior hormonal therapy, we compared the semen parameters of 141
      healthy cisgender sperm bankers and 78 healthy transgender sperm bankers. The
      transgender sperm bankers demonstrated lower sperm concentration, total motile
      sperm count, and post-thaw sperm parameters. The transgender sperm bankers also
      demonstrated a higher incidence of oligozoospermia. CONCLUSIONS: This is the
      largest report to date on the incidence of transgender sperm cryopreservation and
      comparison of semen characteristics with cisgender sperm bankers. The data reveal
      an increased incidence of transgender sperm banking as well as poorer semen
      parameters of transgender individuals compared with cisgender controls.

PMID- 30094957
TI  - Long noncoding RNA MALAT1 regulates HDAC4-mediated proliferation and apoptosis
      via decoying of miR-140-5p in osteosarcoma cells.
AB  - Noncoding RNAs regulate the initiation and progression of osteosarcoma (OS). The
      role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1
      (MALAT1) playing in OS and whether the function it working out was achieved
      through HDAC4 pathway remain uncovered. In this study, we illustrated that MALAT1
      was upregulated and was correlated with poor prognosis in OS patients. Meanwhile,
      we demonstrated that a depression of MALAT1 suppressed proliferation and promoted
      apoptosis in OS cell line HOS and 143B. Further, we verified that MALAT1 exerting
      its function via upregulating of histone deacetylase 4 (HDAC4). Through an online
      prediction, a series of luciferase assays and RNA pull-down assays, we
      demonstrated that both MALAT1 and HDAC4 were the targets of microRNA-140-5p (miR
      140-5p) via sharing a similar microRNA responding elements. Even further, we
      revealed that MALAT1 served as a ceRNA of HDAC4 via decoying of miR-140-5p.
      Finally, we proved that MALAT1 promoted OS tumor growth in an in vivo animal
      study. In summary, the outcomes of this study demonstrated the complex ceRNA
      network among MALAT, miR-140-5p, and HDAC4-mediated proliferation and apoptosis
      in OS. This study might provide a new axial in molecular treatment of OS.

PMID- 30094958
TI  - Circulating monocytes from prostate cancer patients promote invasion and motility
      of epithelial cells.
AB  - BACKGROUND: Recruited myeloid cells are known to promote cancer initiation,
      malignant progression, metastasis, and resistance to therapy in the tumor niche.
      We tested the hypothesis that circulating blood monocytes from advanced prostate
      cancer (PCa) patients exhibit a protumor phenotype and directly influence the
      tumor microenvironment in response to tumor-derived signals. METHODS: Blood
      monocytes from advanced and stable PCa patients were cultured, and the
      conditioned media (CM) were collected and analyzed using standard invasion and
      wound closure assays to measure effects on invasion and motility of PCa tumor
      cells. We then identified the proteome profile of these monocytes using proteome
      array and ELISA. RESULTS: Conditioned media from circulating monocytes in
      patients with metastatic prostate cancer (PCa-M) increased invasion of epithelial
      PCa cells in vitro. Proteome Profiler Analysis revealed that monocyte-derived CM
      from metastatic castration-resistant (mCRPC) patients presented high levels of
      chitinase-3-like 1 (CHI3L1, YKL-40) when compared to patients with stable disease
      (PCa-N) and healthy control individuals (HC). The only described receptor for
      CHI3L1, interleukin-13 receptor alpha2 (IL-13Ralpha2), was significantly up
      regulated in the human metastatic PCa cell line, ARCaPM . Accordingly, we
      observed that the activation of IL-13Ralpha2 from PCa-M CM increased the
      invasiveness of ARCaPM cells while siRNA directed against this receptor
      significantly reduced invasiveness of these cells in the presence of CM from PCa
      M patients. CONCLUSIONS: Thus, we show that circulating monocytes from metastatic
      PCa patients exert a tumor-promoting role via the secretion of CHI3L1, and CHI3L1
      demands further exploration as a possible therapeutic target in advanced PCa.

PMID- 30094959
TI  - Prediction of readmissions and mortality in patients with heart failure: lessons
      from the IMPEDANCE-HF extended trial.
AB  - AIMS: Readmissions for heart failure (HF) are a major burden. We aimed to assess
      whether the extent of improvement in pulmonary fluid content (DeltaPC) during HF
      hospitalization evaluated by lung impedance (LI), or indirectly by other clinical
      and laboratory parameters, predicts readmissions. METHODS AND RESULTS: The
      present study is based on pre-defined secondary analysis of the IMPEDANCE-HF
      extended trial comprising 266 HF patients at New York Heart Association Class II
      IV and left ventricular ejection fraction <= 35% randomized to LI-guided or
      conventional therapy during long-term follow-up. Lung impedance-guided patients
      were followed for 58 +/- 36 months and the control patients for 46 +/- 34 months
      (P < 0.01) accounting for 253 and 478 HF hospitalizations, respectively (P <
      0.01). Lung impedance, N-terminal pro-brain natriuretic peptide, weight,
      radiological score, New York Heart Association class, lung rales, leg oedema, or
      jugular venous pressure were measured at admission and discharge on each
      hospitalization in both groups with the difference defined as DeltaPC. Average LI
      assessed DeltaPC was 12.1% vs. 9.2%, and time to HF readmission was 659 vs. 306
      days in the LI-guided and control groups, respectively (P < 0.01). Lung impedance
      based DeltaPC predicted 30 and 90 day HF readmission better than DeltaPC assessed
      by the other variables (P < 0.01). The readmission rate for HF was lower if
      DeltaPC > median compared with DeltaPC <= median for all parameters evaluated in
      both study groups with the most pronounced difference predicted by LI (P < 0.01).
      Net reclassification improvement analysis showed that adding LI to the
      traditional clinical and laboratory parameters improved the predictive power
      significantly. CONCLUSIONS: The extent of DeltaPC improvement, primarily the LI
      based, during HF-hospitalization, and study group allocation strongly predicted
      readmission and event-free survival time.

PMID- 30094961
TI  - Evaluation of continuous nonaffinity capture chromatography for a recombinant
      enzyme-optimization for a changing perfusion feedstream and comparison to batch
      processing.
AB  - This work presents the optimization and critical evaluation of continuous capture
      chromatography in the downstream process of a recombinant enzyme. For the
      upstream manufacturing of this molecule, a perfusion process was implemented due
      to benefits for product quality and productivity. This process is, however,
      characterized by low titer and significant changes over the course of the harvest
      duration in terms of active enzyme concentration and impurity content. We
      evaluated the feasibility and benefits of a continuous capture operation. This
      case study illustrates the design approach that can be utilized to address
      challenges presented by a changing feedstream, and the statistical measures that
      can be employed to characterize and optimize the operating space under material
      and time constraints. Process economic modeling in conjunction with Monte Carlo
      simulations indicate that even for a nonaffinity capture step utilizing a
      relatively cheap ion-exchange resin, the smaller column volume used in a
      continuous set-up results in cost savings compared to the batch process. We
      compare this option to the scenario of repeated processing using a small capture
      column in batch mode. Our analysis establishes that continuous processing becomes
      economically attractive for processes where only a small portion of the potential
      column lifetime can be utilized or for column steps with slow mass transport and
      shallow breakthrough curves. In cases where column breakthrough is sharp and
      resin lifetime is relatively short, continuous processing may offer an
      improvement over traditional batch processing, but much of the productivity and
      cost savings can be realized through repeated column cycling. (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 2018 (c) 2018 American
      Institute of Chemical Engineers Biotechnol. Prog., 34:1195-1204, 2018.

PMID- 30094960
TI  - Cryptotanshinone suppresses cell proliferation and glucose metabolism via
      STAT3/SIRT3 signaling pathway in ovarian cancer cells.
AB  - Ovarian cancer is the most malignant gynecologic cancer among women worldwide.
      Cryptotanshinone (CT), isolated from Salvia miltiorrhiza Bunge, has been
      identified as a potential therapeutic agent in treating several malignant tumors,
      but the molecular mechanism of CT in ovarian cancer still remains illustrated.
      Here, we sought to elucidate the regulatory function of CT on cell glucose
      metabolism in ovarian cancer. The treatment of CT on ovarian cancer cells
      effectively inhibited glucose uptake and lactate production in ovarian cancer
      cells. The expression levels of glycolysis-related proteins, such as GLUT1, LDHA,
      and HK2, were decreased by the treatment of CT detected by qRT-PCR and
      immunoblotting. Mechanistically, CT exerted its anti-tumor effect by targeting
      STAT3/SIRT3/HIF-1alpha signaling pathway in vitro and in vivo, which could be
      rescued by the introduction of SIRT3 shRNA in ovarian cancer cells. The clinical
      data showed that the expression level of STAT3 in ovarian cancer patients' sera
      and tissues was positively correlated with those of GLUT1, LDHA, HK2 and HIF
      1alpha, but negatively with that of SIRT3These findings provide evidence that CT
      inhibited cellular glycolysis-induced cell growth and proliferation through
      repression of STAT3/SIRT3/HIF-1alpha signaling pathway, indicating that CT may be
      developed as a chemotherapeutic agent to treat ovarian cancer.

PMID- 30094962
TI  - Most calbindin-immunoreactive neurons, but few calretinin-immunoreactive neurons,
      express the m1 acetylcholine receptor in the middle temporal visual area of the
      macaque monkey.
AB  - INTRODUCTION: Release of the neuromodulator acetylcholine into cortical circuits
      supports cognition, although its precise role and mechanisms of action are not
      well understood. Little is known about functional differences in cholinergic
      modulatory effects across cortical model systems, but anatomical evidence
      suggests that such differences likely exist because, for example, the expression
      of cholinergic receptors differs profoundly both within and between species.
      METHODS: In the primary visual cortex (V1) of macaque monkeys, cholinergic
      receptors are strongly expressed by inhibitory interneurons. Using dual
      immunofluorescence confocal microscopy, we examine m1 muscarinic acetylcholine
      receptor expression by two subclasses of inhibitory interneurons-identified by
      their expression of the calcium-binding proteins calbindin and calretinin-in the
      middle temporal extrastriate area (MT) of the macaque. RESULTS AND CONCLUSIONS:
      We find that the majority of calbindin-immunoreactive neurons (55%) and only few
      calretinin-immunoreactive neurons (10%) express the m1 acetylcholine receptor.
      These results differ from the pattern observed in V1 of the same species, lending
      further support to the notion that cholinergic modulation in the cortex is tuned
      such that different cortical compartments will respond to acetylcholine release
      in different ways.

PMID- 30094964
TI  - Gene network variation and alternative paths to convergent evolution in turtles.
AB  - Diversification of the turtle's shell comprises remarkable phenotypic
      transformations. For instance, two divergent species convergently evolved shell
      closing systems with shoulder blade (scapula) segments that enable coordinated
      movements with the shell. We expected these unusual structures to originate via
      similar changes in underlying gene networks, as skeletal segment formation is an
      evolutionarily conserved developmental process. We tested this hypothesis by
      comparing transcriptomes of scapula tissue across three stages of embryonic
      development in three emydid turtles from natural populations. We found that
      alternative strategies for skeletal segmentation were associated with
      interspecific differences in gene co-expression networks. Notably, mesenchyme
      homeobox 2 (MEOX2) and HOXA3-5 were central hubs driving the activity of 2,806
      genes in a candidate network for scapula segmentation, albeit in only one
      species. Even so, scapula muscle overgrowth corresponded to the activity of
      similar myogenic networks in both species. This and other derived developmental
      processes were not observed in the third species, which displayed the ancestral
      (unsegmented) scapula condition. Differential gene expression tests against this
      reference lineage supported histological and network analyses. Our findings
      illustrate that molecular underpinnings of convergent evolution, including during
      the diversification of the atypical turtle "body plan," are influenced by
      variation in underlying developmental processes.

PMID- 30094965
TI  - Comparing predictive abilities of longitudinal child growth models.
AB  - The Bill and Melinda Gates Foundation's Healthy Birth, Growth and Development
      knowledge integration project aims to improve the overall health and well-being
      of children across the world. The project aims to integrate information from
      multiple child growth studies to allow health professionals and policy makers to
      make informed decisions about interventions in lower and middle income countries.
      To achieve this goal, we must first understand the conditions that impact on the
      growth and development of children, and this requires sensible models for
      characterising different growth patterns. The contribution of this paper is to
      provide a quantitative comparison of the predictive abilities of various
      statistical growth modelling techniques based on a novel leave-one-out validation
      approach. The majority of existing studies have used raw growth data for
      modelling, but we show that fitting models to standardised data provide more
      accurate estimation and prediction. Our work is illustrated with an example from
      a study into child development in a middle income country in South America.

PMID- 30094967
TI  - Nutritional quality and organic matter degradability of Brachiaria spp.
      agronomically biofortified with selenium.
AB  - Selenium (Se) fertilisation in grazing systems can improve the quality of animal
      forage, but there are few studies addressing the influence of Se fertilisation on
      the chemical composition and ruminal degradability of forage fertilised with Se.
      The aim of this study was to evaluate the chemical composition and in vitro
      assays of truly degraded organic matter (TDOM), short-chain fatty acids (SCFA)
      total gas (GP) and methane (CH4 ) production of two harvests of Brachiaria
      brizantha cv. Marandu fertilised with urea coated with B, Cu and sodium selenate
      for 0, 10, 20, 40, 80 and 160 g/ha of Se. Selenium content in forage increased
      linearly with the different doses at 30 and 60 days after fertilisation. However,
      doses of 20 and 80 g/ha Se fertilisation yielded positive effects increasing Se
      content and truly degraded organic matter in vitro of Brachiaria brizantha cv.
      Marandu.

PMID- 30094966
TI  - Determination of selected emerging contaminants in freshwater invertebrates using
      a universal extraction technique and liquid chromatography accurate mass
      spectrometry.
AB  - A simple sample preparation method based on a modified liquid-phase extraction
      approach to extract selected pharmaceuticals and personal care products from
      freshwater organisms is described. Extracted samples were analysed using liquid
      chromatography with Q-Exactive plus hybrid quadrupole Orbitrap mass spectrometry,
      using 2.6 MUm C18 media. A 0.1% v/v acetic acid/acetonitrile mobile phase was
      applied over a 20 min gradient. Method detection limits in full scan mode were
      ca. 0.04-2.38 ng of analyte per g of sample. Linearity ranged from 0.9750 to
      0.9996 over the calibration range of 0.01-100 MUg/L; MS mass accuracy was <2 ppm
      for most analytes. This method was applied to quantify six pharmaceuticals and
      personal care products in seven invertebrate samples. For tandem mass
      spectrometry analysis, selection of precursor ions was performed for each
      pharmaceutical, with Mass Frontier software illustrating the fragmentation
      mechanism. Effects of collision energy on intensities of ions was further
      investigated. The tandem mass spectrometry condition resulting in the highest
      signal of respective selected product ion was selected to confirm each
      pharmaceutical, which was initially observed in the full scan mode. Results
      indicate that pharmaceuticals and personal care products found to be present in
      water-ways, may be incorporated into organisms that live in the environment of
      affected water streams.

PMID- 30094963
TI  - Detecting peripersonal space: The promising role of ultrasonics.
AB  - INTRODUCTION: The approach of an external stimulus to the peripersonal space
      (PPS) modifies some physiological measures, including the cerebral blood flow
      (CBF) in the supplementary motor area and premotor cortex. CBF measurement may be
      useful to assess brain activations when producing specific motor responses,
      likely mediated by cortical and subcortical neural circuits. METHODS: This study
      investigated PPS in 15 healthy humans by characterizing the hemodynamic responses
      (pulsatility index, PI; and heart rate, HR) related to different directions of
      movements of individual's hand toward and backward his/her own face, so to
      perturb PPS). RESULTS: We observed that the CBF and HR were enhanced more when
      the stimulated hand was inside the PPS of the face in the passive and active
      condition than when the hand was outside the PPS and during motor imagery task.
      CONCLUSIONS: These results suggest that the modulation of PPS-related brain
      responses depends on specific sensory-motor integration processes related to the
      location and the final position of a target in the PPS. We may thus propose TCD
      as a rapid and easy approach to get information concerning brain responses
      related to stimuli approaching the PPS. Understanding the modulations of brain
      activations during tasks targeting PPS can help to understand the results of
      psychophysical and behavioral trials and to plan patient-tailored cognitive
      rehabilitative training.

PMID- 30094968
TI  - Isolation characterization, virulence potential of Weissella ceti responsible for
      weissellosis outbreak in rainbow trout (Oncorhynchus mykiss) cultured in Mexico.
AB  - Weissella ceti, a Gram-positive nonmotile bacterium, is currently an emerging
      pathogen within rainbow trout (Oncorhynchus mykiss) farms in China, Brazil, the
      United States, and Japan. This study is the first to isolate, identify, and
      characterize W. ceti isolates from rainbow trout farmed in Mexico. In late 2015,
      a severe disease outbreak caused a 60% mortality rate among 20,000 fish. The
      diseased rainbow trout (100-300 g average) exhibited severe cachexia, body
      darkening, abdominal distension, exophthalmia, haemorrhages, and corneal opacity.
      Internally, diseased fish had pale gills; multifocal, disseminated whitish spots
      on the liver; haemorrhages in the swim bladder, ovary, and on the parietal
      surface of the muscle; and hearts with pseudo-membrane formation. Histologically,
      lesions were characterized by corneal oedema, degenerative and necrotic
      hepatitis, and meningitis. A brain (W-1) and kidney (W-2) isolate were identified
      as W. ceti through polyphasic taxonomy, which included phenotypic
      characterization and 16S rRNA sequencing. RAPD and ERIC-PCR analyses demonstrated
      genetic homogeneity among the Mexican isolates. Virulence tests in rainbow trout
      through intraperitoneal W. ceti injections at concentrations of 1 * 104 , 1 * 105
      , and 1 * 106 CFU per fish resulted in cumulative mortality rates of 25%, 62.5%,
      and 87.5%, respectively, as well as the same clinical signs of hemorrhagic
      septicaemia as were recorded for the natural outbreak. The present report is the
      first to confirm the presence of W. ceti in Mexico, thus extending the known
      geographical distribution of this pathogen across the Americas.

PMID- 30094970
TI  - Biomarkers of Individual Foods, and Separation of Diets Using Untargeted LC-MS
      based Plasma Metabolomics in a Randomized Controlled Trial.
AB  - SCOPE: Self-reported dietary intake does not represent an objective unbiased
      assessment. The effect of the new Nordic diet (NND) versus average Danish diet
      (ADD) on plasma metabolic profiles is investigated to identify biomarkers of
      compliance and metabolic effects. METHODS AND RESULTS: In a 26-week controlled
      dietary intervention study, 146 subjects followed either NND, a predominantly
      organic diet high in fruit, vegetables, whole grains, and fish, or ADD, a diet
      higher in imported and processed foods. Fasting plasma samples are analyzed with
      untargeted ultra-performance liquid chromatography-quadruple time-of-flight. It
      is demonstrated that supervised machine learning with feature selection can
      separate NND and ADD samples with an average test set performance of up to 0.88
      area under the curve. The NND plasma metabolome is characterized by diet-related
      metabolites, such as pipecolic acid betaine (whole grain), trimethylamine oxide,
      and prolyl hydroxyproline (both fish intake), while theobromine (chocolate) and
      proline betaine (citrus) were associated with ADD. Amino acid (i.e., indolelactic
      acid and hydroxy-3-methylbutyrate) and fat metabolism (butyryl carnitine)
      characterize ADD whereas NND is associated with higher concentrations of
      polyunsaturated phosphatidylcholines. CONCLUSIONS: The plasma metabolite profiles
      are predictive of dietary patterns and reflected good compliance while indicating
      effects of potential health benefit, including changes in fat metabolism and
      glucose utilization.

PMID- 30094969
TI  - Expression of vasa, piwi, and nanos during gametogenesis in Typosyllis antoni
      (Annelida, Syllidae).
AB  - Although model species have proven to be crucial for developmental biology, the
      evo-devo approach requires a broader picture across phylogeny. Herein, we try to
      expand the range of studied annelids by presenting a transcriptome of Typosyllis
      antoni as a tool for the study of developmental and evolutionary processes in
      Syllidae. Moreover, we provide homologs of the stem-cell markers vasa, piwi, and
      nanos, and investigate their expression patterns in gamete-producing individuals
      for the first time in this group. We found no expression in females, while there
      is a distinct expression pattern in males. Based on this data, we argue that
      spermatogenesis starts in the gonads and finishes in the coelomic cavity, and it
      occurs simultaneously in a large number of segments. Surprisingly, no expression
      of the stem-cell markers was found in the segment addition zone of these
      reproducing animals (stolonizing). Preliminary explanations like a lack of growth
      during stolonization, or the absence of a common genetic program between germ and
      somatic stem cells, are discussed. Finally, no reservoir of primordial cells has
      been detected, suggesting a possible epigenic origin of the Primordial Germ Cells
      of this species, though this hypothesis needs to be further investigated.

PMID- 30094971
TI  - United States feedlot operator willingness to pay for disposal capacity to
      address foreign animal disease risk.
AB  - Foreign animal diseases can cause severe and lasting economic impacts to
      producers, directly and indirectly. Understanding producer investment cost
      structures can provide industry and policy makers better tools to encourage
      biosecurity adoption. Consistent with the literature, many factors can contribute
      to an individual operator's decision to invest in biosecurity based on individual
      characteristics, perception of disease likelihood, or expected losses associated
      with a disease event. We used a producer survey and a one-and-one-half bound
      econometric model to estimate feedlot operator willingness to pay to invest in
      disposal capacity within the next 3 years. Results indicate an average
      willingness to pay of $14,310 for a one-time investment in on-farm disposal
      capacity to address carcass movement restrictions during a disease outbreak. We
      found several factors that contribute to and explain the heterogeneity between
      feedlots and their adoption decisions. Primarily, size of the feedlot and death
      loss rate significantly impact adoption, which both potentially speak to the
      financial liquidity and investment potential of a feedlot enterprise. While there
      is no failsafe in disease prevention, these results provide a better
      understanding for how to study and structure policy and cost structures to
      incentivize adoption of biosecurity.

PMID- 30094973
TI  - [Unraveling Mysteries of Correlation Between Meridians and Viscera in Connection
      Between Upper and Lower, Interior and Exterior of the Human Body].
AB  - The theory that meridians connect the upper and lower, interior and exterior of
      the whole human body comes from the clinical experience of acupuncture therapy
      mainly by choosing the acupoints of 12 regular meridians at the four limbs.
      During the process of merging the theories of meridians and Zangfu-organs
      (viscera), the expression of the intrinsic relationship of such connection
      gradually becomes more and more complicated. Therefore, the study on the
      correlation between the meridian and viscus should start from the characteristics
      of the meridian theory itself, and discriminate the "reasonable and unreasonable"
      components of the related theoretical descriptions in the literature in order to
      explore the scientific values of this correlation. Based on this viewpoint, the
      present article makes a brief analysis on this proposition from the following two
      angles of view: the understan-ding of such proposition and the historical
      evolution of the meridian theory.

PMID- 30094972
TI  - Needle-based optical coherence tomography for the detection of prostate cancer: a
      visual and quantitative analysis in 20 patients.
AB  - Diagnostic accuracy of needle-based optical coherence tomography (OCT) for
      prostate cancer detection by visual and quantitative analysis is defined. 106
      three-dimensional (3-D)-OCT data sets were acquired in 20 prostates after radical
      prostatectomy and precisely matched with pathology. OCT images were grouped per
      histological category. Two reviewers performed blind assessments of the OCT
      images. Sensitivity and specificity for malignancy detection were calculated.
      Quantitative analyses by automated optical attenuation coefficient calculation
      were performed. OCT can reliably differentiate between fat, cystic, and regular
      atrophy and benign glands. The overall sensitivity and specificity for malignancy
      detection was 79% and 88% for reviewer 1 and 88% and 81% for reviewer 2.
      Quantitative analysis for differentiation between stroma and malignancy showed a
      significant difference (4.6  mm  -  1 versus 5.0  mm  -  1 Mann-Whitney U-test p 
      <  0.0001). A Kruskal-Wallis test showed a significant difference in median
      attenuation coefficient between stroma, inflammation, Gleason 3, and Gleason 4
      (4.6, 4.1, 5.9, and 5.0  mm  -  1, respectively). However, attenuation
      coefficient varied per patient and a related-samples Wilcoxon signed-rank test
      showed no significant difference per patient (p  =  0.17). This study confirmed
      the one to one correlation of histopathology and OCT. Precise matching showed
      that most histological tissues categories in the prostate could be distinguished
      by their unique pattern in OCT images. In addition, the optical attenuation
      coefficient can play a role in the differentiation between stroma and malignancy;
      however, a per patient analysis of the optical attenuation coefficient did not
      show a significant difference.

PMID- 30094974
TI  - [Effect of Electroacupuncture at Different Acupoints on Expression of NGF and
      TrkA in Cerebral Cortex in Rats with Myocardial Ischemia].
AB  - OBJECTIVE: To compare the therapeutic effect of electroacupuncture (EA) of
      "Shenmen" (HT 7, Yuan point of the Heart Meridian), "Zhizheng" (SI 7, Luo point
      of the Small Intestine Meridian) and "Xinshu" (BL15, Back-shu point) on the
      expression of nerve growth factor (NGF) and its receptor, tyrosine kinase A
      (TrkA) in the cerebral cortex of myocardial ischemia (MI) rats. METHODS: A total
      of 70 male SD rats were randomized into sham operation (sham, n=10), model, HT 7,
      SI 7, and BL15 groups (n=15 in each of the latter 4 groups). The MI model was
      established by ligation of the anterior descending branch of the left coronary
      artery. EA (1 mA, 2 Hz) was respectively applied to HT 7, SI 7 and BL15 for 15
      min, once per day for 1 week. Immunohistochemistry and real-time fluorescent
      quantitative PCR were used to detect the expression of NGF and TrkA proteins and
      genes in the cerebral cortex. RESULTS: Compared with the sham group, no
      significant changes were found in the number of NGF immune-reaction (IR)-positive
      and TrkA IR-positive cells, and the expression levels of NGF mRNA and TrkA mRNA
      in the model group (P>0.05). After EA intervention, the number of NGF and TrkA IR
      positive cells and the expression of NGF mRNA and TrkA mRNA in each of the 3 EA
      groups were significantly increased relevant to the model group (P<0.01, P<0.05).
      The effect of EA at BL 15 was significantly superior to that of EA at HT 7 and SI
      7 in increasing the number of NGF and TrkA positive cells and up-regulating the
      expression of their mRNAs (P<0.01, P<0.05). CONCLUSION: EA at HT 7, SI 7 and BL
      15 can increase the levels of expression of NGF and TrkA proteins and mRNAs in
      the cerebral cortex of subacute MI rats and the effects of EA-BL 15 are obviously
      superior to those of EA-HT 7 and EA-SI 7, suggesting a relative specificity of
      the effect of EA at different acupoints.

PMID- 30094975
TI  - [Effect of Electroacupuncture at "Shenmen" (HT 7)- "Tongli" (HT 5) of Heart
      Meridian on Neuronal Activities in Paraventricular Nucleus of Hypothalamus in
      Myocardial Ischemia Rats].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of
      "Shenmen" (HT 7) - "Tongli" (HT 5) segment of the Heart Meridian on neuronal
      electrical activities of hypothalamic paraventricular nucleus (PVN) in rats with
      myocardial ischemia (MI), so as to investigate its possible mechanism underlying
      improvement of MI. METHODS: Thirty-two SD rats were randomly divided into sham
      control, model, HT 7-HT 5 and "Taiyuan" (LU 9)- "Lieque" (LU 7) groups (n=8 in
      each group). EA preconditioning (2 Hz, 1 V, 20 min) was applied to bilateral HT 7
      HT 5 and bilateral LU 9-LU 7, respectively, once everyday for 7 days. The
      electrical activities of the right PVN region were recorded by the implanted
      microelectrode array(2*4)and Plexon multi-channel acquisition system. Cluster
      analysis of neuronal signals was carried out by Offline Sorter software. The
      discharge waveforms, autocorrelation and cross-correlation of neuronal activities
      were analyzed by using Neuro Explorer software. RESULTS: Cluster analysis of
      neuronal signals showed that 2, 2, 1 and 1 interneuron in the sham, model, HT 7
      HT 5, and LU 9-LU 7 groups, and 3 pyramidal neurons in the HT 7-HT 5 were
      acquired. Cross correlation analysis showed that the SPK 02 a and SPK 02 b
      neurons of the HT 7-HT 5 group had an inhibitory relationship. The total
      discharge frequency was significantly increased in the model group relevant to
      the sham group (P<0.01), and was markedly lower in the HT 7-HT 5 group than in
      the model group and LU 9-LU 7 group (P<0.01). Real-time spectrum analysis showed
      that the local field potential spectrum energy of the HT 7-HT 5 group was
      significantly lower than that of the model group and the LU 9-LU 7 group.
      CONCLUSION: EA of HT 7-HT 5 segment of the Heart Meridian can inhibit the
      electrical activity of interneuron and activate the electrical activity of
      pyramidal neuron in PVN region, and an inhibitory relationship exists between the
      interneuron and pyramidal neuron in MI rats, which may be a mechanism of EA in
      regulating activities of the ischemic heart.

PMID- 30094976
TI  - [Neuronal Correlation Between Acupoint BL 23 and the Adrenal Gland in Rats].
AB  - OBJECTIVE: To explore the neuroanatomical basis of acupoint-visceral correlation
      by studying the distribution of the neurons associated with acupoint "Shenshu"
      (BL 23) area and adrenal gland in rats. METHODS: AF 488-CTB and AF 594-CTB were
      injected into the left side of BL 23 area and adrenal gland in the same rat
      respectively. Three days after injection, the dorsal root ganglions (DRG),
      sympathetic chain, and spinal cord were dissected out from the perfused rats. The
      neuronal labeling with AF 488/594-CTB was directly observed on the sections under
      a fluorescent microscope or a laser scanning confocal microscope. RESULTS: All
      neural labeling was observed in the injection side. The sensory neurons
      associated with both acupoint BL 23 and adrenal gland distributed from thoracic
      (T) 10 to lumbar (L) 2 DRG with high concentration in T 12-T 13 and T 11-T 12,
      respectively, in which some of them were simultaneously labeled with both AF
      488/594-CTB and located in T 12-L 1 DRG. For the sympathetic innervation, the
      postganglionic neurons correlated with BL 23 and adrenal gland were labeled with
      AF 488/594-CTB separately in the sympathetic chain at the lumbar segments, while
      the labeled preganglionic neurons were only observed at the lateral horn of T 11
      T 13 spinal segments in the cases of adrenal gland. In addition, the labeled
      motor neurons were mainly detected in the spinal ventral horn at cervical (C) 7-C
      8 and T 11-L 1 segments. CONCLUSION: These results indicate that there are
      segmental correlation between BL 23 and adrenal gland on the sensory and
      sympathetic innervations, and this correlation might be a neural pathway for
      modulating the function role of adrenal gland through BL 23 needling.

PMID- 30094977
TI  - [Electroacupuncture of "Tianshu" (ST 25) Suppresses Visceral Pain Possibly by
      Down-regulating Mast Cell Activation, and Tryptase and SP Expression in Rats with
      Post-infectious Irritable Bowel Syndrome].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25)
      on visceral pain and colonic mast cell (MCs) number and tryptase and SP
      expression in post-infectious irritable bowel syndrome (PI-IBS) rats, so as to
      reveal its mechanisms underlying improvement of PI-IBS. METHODS: Forty-five
      female Wistar rats were randomly divided into control, model and EA groups (15
      rats/ group, 3 rats/group used for H. E. staining, and 12 rats/group for
      immunohistochemistry). The PI-IBS model was established by intra-anal injection
      of mixed liquor of 50% ethyl alcohol and trinitro-benzene-sulfonic acid (TNBS).
      EA (2 Hz/15 Hz, 0.5-1.0 mA) was applied to bilateral "Tianshu" (ST 25) for 30
      min, once every day for 14 days. The visceral pain was measured by abdominal
      withdrawal reflex (AWR), for which the rectal implanted air balloon was dilated
      by infusion of normal saline. The histopathological changes of the colon tissue
      were observed after H. E. staining, and the colonic MCs were displayed by
      Toluidine blue staining. The expression of tryptase and SP proteins in the colon
      specimens were detected by immunohistochemistry. RESULTS: The AWR threshold was
      significantly lowered in the model group relevant to the control group (P<0.05)
      and considerably increased after EA intervention in comparison with the model
      group (P<0.05). The number of MCs and the expression levels of colonic tryptase
      and SP proteins in the colon tissues were significantly higher in the model group
      than in the control group (P<0.05), and obviously lower after EA intervention in
      the EA group than in the model group (P<0.05). CONCLUSION: EA of "Tianshu" (ST
      25) can inhibit visceral pain in PI-IBS rats, which may be associated with its
      effects in activating MCs and down-regulating the expression of tryptase and SP
      proteins in the colonic tissues.

PMID- 30094979
TI  - [Current Researches and Ideas Regarding Correlation Between Meridians and
      Viscera].
AB  - The correlation between meridians and viscera is the key content of the meridian
      theory in acupuncture medicine. This paper introduces the close relationship
      between the meridians running on the body surface and viscera from ancient lite
      rature, modern experimental studies (such as acupoint sensitization, neuro
      endocrine-immune networks, etc.), and clinical application in the treatment of
      various conditions with acupuncture, moxibustion, Guasha (scraping) therapies,
      etc. We also presented some related research ideas (i.e., taking the clinical
      treatment as the forerunner, paying more attention to multi-disciplinary
      integration, combining clinical and basic research together, doing research from
      tridimensional point of review, and making full use of advanced technology, etc.)
      in order to provide a possibly favorable help for researchers to further reveal
      the scientific mechanisms underlying correlation between the meridian and viscera
      in the future.

PMID- 30094978
TI  - [Analysis on Correlation Between Meridians and Viscera in Book The Yellow
      Emperor's Internal Classic].
AB  - The meridians and Zangfu-organs (viscera) are two major systems in the basic
      theory of traditional Chinese medicine (TCM). They were primarily emerged
      together in simple form possibly in the Han Dynasty shown by the unearthed silk
      manuscripts of Changsha Mawangdui Han Tomb, and became a systematic theory in
      classical book "Neijing" (The Yellow Emperor's Internal Classic). After
      classification of the meridians' disease manifestations described in book "Ling
      Shu-Jing Mai" (Miraculous Pivot: Meridians) we found that more than half of the
      manifestations appear along the running course of meridians. The symptoms and
      signs of disorders of the meridians correlated with viscera which have the same
      name in western medicine account for approximately 10%, and the rest pathologic
      manifestations correlated with the viscera in terms of TCM are approximately 30%.
      Current researches about meridian and viscera mainly focus on viscera,
      particularly on the stomach and heart. The researches on meridians and viscera
      that use real-time effects of acupuncture as indicators have a complicated
      relationship with the nerve segments, which presented as that "multiple meridians
      control one viscus" and the specificity of meridian. Our chronic experiment about
      blocking the meridians suggested an association between meridian and pathologic
      manifestations of viscera. Physical index measurement and mathematical analysis
      can verify certain patterns of meridian-physical appearances, which would be a
      direction for future meridian research. The stabilities of visceral functions
      rely on negative feedback regulation, which are probably realized by way of
      somatic and visceral afferent and efferent nerves and volume transmission of the
      tissue fluid channels of meridians. Therefore, signals of acupuncture stimulation
      of the distant acupoints might be transmitted to the central nervous system
      through neurohumor relay, open of the "negative feedback channels of meridians",
      achieving a bidirectional regulation, and at the same time, producing a
      phenomenon of "sensation propagated along the meridian" during signal
      transmission.

PMID- 30094981
TI  - [Manual Acupuncture Stimulation Regulates Expression of Receptor Activity
      modifying Protein 1 and 5-HT 1 D Receptor Proteins and Genes in Migraine Rats].
AB  - OBJECTIVE: To observe the effect of liver-soothing and mental-activity-regulating
      (LSMAR) needling on the expression of receptor activity-modifying protein 1 (RAMP
      1, receptor of calcitonin gene-related peptide), 5-hydroxytryptamine 1 D
      receptor(5-HT 1 DR) in the spinal trigeminal nucleus (STN) and midbrain in
      migraine rats, so as to explore its underlying mechanism in relieving migraine.
      METHODS: A total of 40 male Wistar rats were randomly divided into control,
      model, LSMAR and conventional needling groups (n=10 rats in each). The migraine
      model was established by subcutaneous injection of nitroglycerin at the posterior
      neck. LSMAR was applied to "Baihui" (GV 20), bilateral "Fengchi" (GB 20),
      "Neiguan" (PC 6) and "Taichong" (LR 3) in the LSMAR group and conventional
      needling was applied to "Baihui" (GV 20) and bilateral "Fengchi" (GB 20) in the
      conventional acupuncture group for 30 min, once a day for 8 days before modeling.
      The expression levels of RAMP 1 and 5-HT 1 DR proteins and mRNAs in the STN and
      mesencephalon were detected by real-time fluorescent quantitative PCR and Western
      blot, separately. RESULTS: Compared with the control group, the expression levels
      of RAMP 1 protein and mRNA in STN and mesencephalon were significantly increased
      (P<0.05) and those of 5-HT 1 DR protein and mRNA considerably decreased (P<0.05)
      in the model group. After the acupuncture treatment, the increased levels of RAMP
      1 protein and mRNA and the decreased levels of 5-HT 1 DR protein and mRNA in the
      STN and midbrain were obviously reversed in the LSMAR and conventional needling
      groups relevant to the model group (P<0.05). The effect of LSMAR needling was
      significantly superior to that of conventional needling in down-regulating the
      expression levels of RAMP 1 mRNA and protein in the STN and mesencephalon
      (P<0.05) and in up-regulating the expression levels of 5-HT 1 DR mRNA and protein
      in the two brain regions (P<0.05). CONCLUSION: Manual acupuncture stimulation of
      GV 20, GB 20, etc. can inhibit the expression of RAMP 1 protein and mRNA in the
      STN and midbrain, and up-regulate the expression of 5-HT 1 DR in the two brain
      regions of migraine rats, which may be related to its effect in relieving
      migraine.

PMID- 30094980
TI  - [Subcutaneous Metabolites Involving Acupoint Sensitization Induced by Myocardial
      Ischemia and Acupuncture Stimulation in Rabbits].
AB  - OBJECTIVE: The present study aimed at observing the profile of metabolites in
      sensitized acupoints induced by myocardial ischemia (MI) and the effect of
      acupuncture intervention on the changes of the metabolites so as to explore the
      material basis of acupoint sensitization. METHODS: A total of 20 New Zealand
      rabbits were randomly and equally divided into a control group and a model group.
      The MI model was established by occlusion of the anterior descending branch of
      the left coronary artery with a controllable air balloon inflation method for 5
      min/time, twice a day (4-hours' interval) for continuous 5 days (the first stage
      of MI). After one day's rest, another 5 days' occlusion was conducted again (the
      second stage of MI) in the same way. The rabbits of the control group were
      treated with the same procedures but without occlusion. Subcutaneous
      microdialysis fluid samples were collected from "Neiguan" (PC 6), "Shenmen" (HT
      7), "Xinshu" (BL 15), and "Taixi" (KI 3) regions on day 8(after recovery from
      operation), 14 (the first stage of MI), and 20 (the second stage of MI), as well
      as collected from PC 6 region during and post-acupuncture stimulation of PC 6,
      respectively. Manual acupuncture stimulation was applied to the right PC 6 for 30
      min. Partial least squares -linear discriminant analysis (PLS-DA) was used to
      identify different metabolism patterns of the microdialysis fluid sample between
      groups and at different time-points in the same one group, and the distinct
      metabolites as the potential markers between groups were weighted via the values
      of variable importance in the projection (VIP) in combination with t-test
      analysis. An area under the curve (AUC) >1.0 indicated a test exhibiting good
      discrimination between groups. RESULTS: Six metabolites identified to be
      significantly different between the control and model groups were L-glutamic
      acid, phenylalanine and 3-hydroxyisobutyric acid (which were significantly
      increased relevant to the control group), and L-histidine, octadecanedioic acid
      and 9-keto palmitic acid (significantly decreased relevant to the control group)
      in the microdialysate of PC 6, HT 7 and BL 15 regions. In the microdialysate of
      PC 6, 4 metabolites including L-glutamic acid, octadecanedioic acid and 8
      isohydroxy PGF 2 alpha (significantly increased), as well as L-histidine
      (markedly decreased) were identified to be considerably different between the
      model and control groups. After acupuncture for 30 min, the AUC level of L
      glutamic acid was further significantly increased (P<0.05), that of L-histidine
      obviously decreased, and those of octadecanedioic acid and 8-isohydroxy PGF 2
      alpha turned back nearly to the level of pre-MI. CONCLUSION: L-glutamic acid,
      phenylalanine, 3-hydroxyisobutyric acid, L-histidine, octadecanedioic acid and 9
      keto palmitic acid from PC 6, HT 7 and BL 15 regions may be used as the material
      biomarker for MI-induced sensitization of these acupoints. Manual acupuncture
      intervention of PC 6 induces a significant change of L-histidine and L-glutamic
      acid in the local subcutaneous tissues.

PMID- 30094982
TI  - [Electroacupuncture Improves Limb Locomotor Function Possibly by Suppressing Rho
      ROCK II Pathway Related Factors in Anterior Horns of Spinal Cord in Rats with
      Acute Spinal Cord Injury].
AB  - OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Jiaji" (EX-B 2)
      on limb locomotor function and expression of Ras homolog gene family member A
      (RhoA), Rho-associated kinase II (ROCK II) and myosin light chain (MLC) proteins
      in the anterior horn of spinal cord in acute spinal cord injury (ASCI) rats, so
      as to explore its mechanisms under-lying improvement of SCI-induced limb
      locomotor dysfunction. METHODS: Forty-eight female Wistar rats were randomly
      divided into sham operation (sham), ASCI model (model), EA EX-B 2 (EA) and ROCK
      inhibitor (Fasudil) groups which were further divided into 14 d and 28 d
      subgroups (n=6 in each). The ASCI model was made by using weight drop striking
      method. Three hours after modeling, EA (100 Hz, 0.4, 0.6 mA) was applied to EX-B
      2 (T 9, T 11) for 30 min, once daily for 14 d and 28 d, respectively. The ROCK
      inhibitor (hydrochloride Fasudil, 10 mg/kg) was administrated by intraperitoneal
      injection immediately after modeling, once a day, continuously for 14 d or 28 d.
      The expression of RhoA, ROCK II and MLC proteins in the spinal cord anterior horn
      tissue (T 10) was detected by immunohistochemistry. The rats' hindlimb locomotor
      function was assessed according to Basso, Beattie and Bresnahan (BBB) locomotor
      rating scale (21-points). RESULTS: After ASCI, the BBB scores were significantly
      lower in the model group than in the sham group on day 14 and 28 (P<0.05), and
      obviously higher in the EA and inhibitor groups than in the model group (P<0.05),
      suggesting an improvement of the hindlimb locomotor function after EA
      intervention or suppression of ROCK. Immunohistochemical results indicated that
      the numbers of RhoA, ROCK II and MLC immune-reaction positive cells in the
      anterior horn of spinal cord were significantly more in the model group than in
      the sham group (P<0.05), and remarkably decreased in both EA and inhibitor groups
      on day 14 and 28 relevant to the model group (P<0.05). The therapeutic effects of
      EA were markedly weaker than those of inhibitor Fasudil in up-regulating BBB
      score and down-regulating the number of RhoA, ROCK II and MLC positive cells
      (P<0.05). CONCLUSION: EA of EX-B 2 can improve the hindlimb locomotor function in
      ASCI rats, which may be associated with its effect in down-regulating the
      expression of RhoA, ROCK II and MLC proteins (i.e., inhibiting the RhoA/ROCK
      signaling pathway) in the anterior horn of spinal cord.

PMID- 30094983
TI  - [A Randomized Controlled Clinical Trial of Treatment of Moderate and Severe
      Persistent Allergic Rhinitis of Spleen Deficiency Pattern by Herbal Cake
      partitioned Moxibustion Combined with Rhinocort Nasal Spray].
AB  - OBJECTIVE: To evaluate the clinical effect of herbal cake-partitioned moxibustion
      combined with medication in the treatment of moderate and severe persistent
      allergic rhinitis (PAR) patients of spleen deficiency pattern. METHODS: Sixty
      patients with moderate and severe PAR of spleen deficiency pattern were
      randomized into medication (Rhinocort) group and herbal cake-partitioned
      moxibustion combined with medication group (combination group, n=30 cases in
      each). Medicinal cake-partitioned moxibustion was applied to Yintang (GV 29, for
      about 20 min), Shenque(CV 8, about 50 min), bilateral Zusanli (ST 36, about 40
      min)and Hegu(LI 4, about 40 min)once every other day for successive 8 weeks. All
      the patients received treatment with Rhinocort nasal spray, 2 jets/day for each
      nostril (64 ug/jet) for 8 weeks. The patients' conditions (symptoms of nasal
      sufferings, sleeping, sniffle, eye, emotion, etc.) were assessed by visual
      analogue scale (VAS) and rhino conjunctivitis quality of life questionnaire
      (RQLQ, 24 items of 7 aspects, 0-6 points/item), respectively. The spleen
      deficiency syndrome score was determined according to "Guiding Principles for
      Clinical Research of New Drugs of Chinese Materia Medica" (2002). The therapeutic
      effect was assessed by referring to "the Diagnostic and Therapeutic Principles
      and Recommended Schemes for Allergic Rhinitis" (2004). RESULTS: Following the
      treatment, the scores of VAS, RQLQ, spleen deficiency syndrome were significantly
      decreased on the 4thand the 8th week of treatment in both groups in comparison
      with those of their own individual pre-treatment (P<0.05, P<0.01). Four weeks'
      follow-up survey showed that the VAS score and RQLQ score of the combination
      group were obviously lower than those of the medication groups (P<0.05),
      suggesting a better post-effect of moxibustion. Of the two 30 cases in the
      medication and combination groups, 9 and 9 experienced marked improvement in
      their symptoms, 16 and 17 were effective, and 5 and 4 ineffective, with the
      effective rate being 83.3% and 86.7%, respectively. No significant differences
      were found between the two groups in the VAS and RQLQ scores on the 4th and 8th
      week during treatment and in the effective rate (P>0.05). CONCLUSION: Herbal cake
      partitioned moxibustion combined with hormone (Rhinocort) nasal spray is
      effective in relieving symptoms of moderate and severe PAR patients of spleen
      deficiency syndrome, and has a better post-effect.

PMID- 30094984
TI  - [Electroacupuncture of Hegu(LI 4) and Sanyinjiao(SP 6) Assists Medicinal
      Abortion].
AB  - OBJECTIVE: To observe the effectiveness of electroacupuncture (EA) therapy in
      promoting medicinal abortion. METHODS: Sixty participants with early pregnancy
      were randomly divided into medication (control) and EA+ medication groups (n=30
      in each). Participants in the control group were treated by regular medication
      (mifepristone and misoprostol tablets), and those of the EA group were treated by
      EA stimulation (2 Hz/100 Hz, a tolerable strength) of bilateral Hegu(LI 4) and
      Sanyinjiao(SP 6) for 25 min, and also by the same medication method mentioned in
      the control group. Participants of both groups were admitted to the hospital for
      observation on the 3rd day after taking medication. The abdominal pain was
      assessed by visual analogue scale (VAS) score, and the foetal sac discharge
      duration and the complete abortion rate were recorded. RESULTS: After the
      treatment, the VAS scores of both groups were significantly reduced in comparison
      with their own pre-treatment in each group (P<0.01), and the VAS score of the EA+
      medication group was significantly lower than that of the medication group
      (P<0.01). The foetal sac discharge duration was significantly shorter in the EA+
      medication group than in the medication group (P<0.01). The abortion rates showed
      no significant difference between the two groups (P>0.05). CONCLUSION: EA
      stimulation of Hegu(LI 4) and Sanyinjiao(SP 6) has a positive effect in assisting
      medicinal abortion in reducing abdominal pain and shortening foetal sac discharge
      duration.

PMID- 30094985
TI  - Correction: McDonald et al., Alterations in Cytosolic and Mitochondrial [U
      13C]Glucose Metabolism in a Chronic Epilepsy Mouse Model (eNeuro
      November/December 2017, 4(1) e0341-16.2017 1-11
      https://doi.org/10.1523/ENEURO.0341-16.2017).
AB  - [This corrects the article DOI: 10.1523/ENEURO.0341-16.2017.][This corrects the
      article DOI: 10.1523/ENEURO.0341-16.2017.].

PMID- 30094986
TI  - Voltage Control of Magnetic Anisotropy through Ionic Gel Gating for Flexible
      Spintronics.
AB  - In spite of recent rapid development of flexible electronics, voltage-tunable
      spintronic structures and devices on flexible substrates have been rarely
      studied. Here, voltage control of magnetic anisotropy (VCMA) is demonstrated via
      ionic gel (IG) gating on flexible polyimide substrates with a circuit operating
      voltage of 1.8 V. A reversible, nonvolatile VCMA switching of 114 Oe is achieved
      in Pt/Fe/Pt multilayer, where the spatial magnetic anisotropy distribution is
      determined quantitatively by electron spin resonance technique. This IG gating
      process is repeatable as the substrates are under different bending conditions.
      The voltage modulation of magnetic anisotropy through IG gating with excellent
      flexibility proposes potential applications in low-power wearable spintronic
      devices.

PMID- 30094987
TI  - Robust, Highly Visible, and Facile Bioconjugation Colloidal Crystal Beads for
      Bioassay.
AB  - High mechanical strength, highly visible, and admirable grafting molecular
      ability is the key challenge for colloidal photonic crystal (CPC) barcode beads
      in multiplex analysis fields. To achieve this goal, we proposed self-adhesion
      particles, polydopamine-coated SiO2 nanoparticles (PDA@SiO2), to construct CPC
      barcode beads by droplet-based microfluidic approach. Because of the adhesion,
      broad absorption of light, and "active" functional groups of PDA, the beads are
      endowed with high robustness, visibility, and excellent biomolecule
      immobilization. Ultrasonic treatment and compression experiments demonstrated
      that PDA@SiO2 CPC barcode beads have a high mechanical strength. Color analysis
      illustrated that PDA@SiO2 CPC beads exhibited a high visibility in color. The
      verification of fluorescent-tagged biomolecule conjugation together with the
      antigen detection stated that PDA@SiO2 CPC beads are capable of immobilizing
      biomolecule by covalent binding. With a sandwich format, the beads were applied
      to analyze the tumor makers including alpha fetal protein, carcinoembryonic
      antigen, and prostate specific antigen from practical clinical serum. The
      proposed suspension arrays using PDA@SiO2 CPC beads as a barcode showed
      acceptable accuracy and detection reproducibility.

PMID- 30094988
TI  - Bifunctional Role of LiNO3 in Li-O2 Batteries: Deconvoluting Surface and
      Catalytic Effects.
AB  - Out of the many challenges in the realization of lithium-O2 batteries (LOB), the
      major is to deal with the instability of the electrolyte and the cathode
      interface under the stringent environment of both oxygen reduction and evolution
      reactions. Lithium nitrate was recently proposed as a promising salt for LOB
      because of its capability to stabilize the lithium anode by the formation of a
      solid electrolyte interphase, its low level of dissociation in aprotic solvents,
      and its catalytic effect toward oxygen evolution reaction (OER) in rechargeable
      LOB. Nevertheless, a deeper understanding of the influence of nitrate on the
      stability and electrochemical response of the cathode in LOB is yet to be
      realized. Additionally, it is well accepted that carbon instability toward
      oxidation is a major reason for early failure of LOB cells; therefore, it is
      essential to investigate the effect of electrolyte components on this side of the
      battery. In the present work, we show that nitrate leads to interfacial changes,
      which result in the formation of a surface protection domain on the carbon
      scaffold of LOB cathode, which helps in suppressing the oxidative damage of the
      carbon. This effect is conjugated with an additional electrocatalytic effect of
      the nitrate ion on the OER. Using in operando online electrochemical mass
      spectroscopy, we herein deconvolute these two positive effects and show how they
      are dependent on nitrate concentration and the potential of cell operation. We
      show that a low amount of nitrate can exhibit the catalytic behavior; however, in
      order to harness its ability to suppress the oxidative damage and passivate the
      carbon surface, an excess of LiNO3 is required.

PMID- 30094989
TI  - Mechanical Reliability of Flexible Encapsulated Organic Solar Cells:
      Characterization and Improvement.
AB  - The encapsulation of organic photovoltaic (OPV) devices can help mitigate the
      degradation induced by environmental factors like water and oxygen and thus
      potential to increase OPV lifetime. Because flexibility is an important parameter
      for targeted OPV applications, this paper proposes a fundamental study on the
      impact of the roll-to-roll flexible encapsulation process. Both performance and
      mechanical reliability of encapsulated devices have been scouted. Furthermore, it
      has been demonstrated that a relatively simple peeling technique allows
      understanding the role of the interfaces inside a multilayered OPV device
      supported by a flexible poly(ethylene terephthalate) substrate. For this purpose,
      the peeling strengths between each layer were measured using a series of partial
      devices. This provided a quantitative analysis of the mechanical strength or
      quality of each interface. Two interfaces revealed pronounced weaknesses: active
      layer with hole transporting layer and transparent conducting electrode with
      electron transporting layer. Among various surface treatments applied to improve
      these interfaces, an optimized UV-ozone (UVO3) treatment proved to modify
      substantially the surface properties of used zinc oxide (ZnO) and thus improved
      its adhesion to the neighboring layers. The physicochemical and structural
      changes of ZnO have been confirmed by IR spectroscopy and contact angle
      measurements. It has also been shown that better interfaces within the device
      improve the overall performance of the devices and their resilience to roll-to
      roll encapsulation.

PMID- 30094990
TI  - Reconstituting Glioma Perivascular Niches on a Chip for Insights into
      Chemoresistance of Glioma.
AB  - In this work, we report the direct diagnosing chemoresistance of glioma stem
      cells (GSCs) during chemotherapy on a biomimetric microsystem that reconstitutes
      glioma perivascular niches on a chip. Glioma stem cells and endothelial cells
      were specially cocultured onto the biomimetric system to precisely control stem
      cell coculture for the proof-of-principle studies. The expression levels of 6- O
      methylguanine was confirmed by mass spectrometer, and Bmi-1 gene was also
      investigated to uncover the chemoresistance of GSCs. The results demonstrated
      that the formation of perivascular niches effectively maintains the glioma stem
      cells at a pluripotent status owing to their successful cellular interactions. A
      stronger chemoresistance of glioma stem cells was confirmed by the formation of
      the GSCs neurosphere, the expression levels of 6- O-methylguanine and Bmi-1 gene.
      The vital role of endothelial cells in chemoresistance was demonstrated. The
      chemoresistance reported in this work will contribute to glioma therapy.

PMID- 30094992
TI  - Assembly of Two Metal-Organic Frameworks Based on Distinct Cobalt Dimeric
      Building Blocks Induced by Ligand Modification: Gas Adsorption and Magnetic
      Properties.
AB  - Solvothermal reaction of 3,5-di(pyridin-4-yl) benzoic acid (HDPB) with Co(II)
      leads to a novel metal-organic framework, [Co2O(DPB)2(DMF)2]. xS (1), which
      represents a rare reo-type net with trigonal prismatic cobalt dimer,
      [Co2O(CO2)2N4], as building blocks to construct a 3D framework containing three
      different types of nanoscale M12L12 and M24L12 polyhedron cages. More
      interestingly, under the same condition, the assembly of 4-methyl-3,5-di(pyridin
      4-yl) benzoic acid (HMDPB) with Co(II) facilitates the formation of a cationic
      framework, [Co2(MDPB)3(DMF)](NO3). xS (2), with cobalt dimer, [Co2(CO2)3N4], as
      building blocks. Complex 2 represents the first example of a zeolite-like network
      with 48-nuclear SOD cage. The significant effect of subtle modification of ligand
      on the overall MOFs is discussed. Moreover, the gas adsorption studies reveal
      that 1 exhibits permanent porosity and selective CO2 uptake. Variable-temperature
      magnetic susceptibility measurements show that both 1 and 2 exhibit
      antiferromagnetic behavior.

PMID- 30094991
TI  - Designed Construction of Cluster Organic Frameworks from Lindqvist-type
      Polyoxovanadate Cluster.
AB  - Two unprecedented examples of cluster organic frameworks
      (TBA)3Cu[V6O13(L)2]2.4DEF (2) (TBA)Ag[V6O13(L)2] solvent (3) (TBA =
      tetrabutylammonium, H3L = tris(hydroxymethyl)-4-picoline, DEF = N, N'
      diethylformamide) based on Lindqvist-type polyoxometalate (POM) secondary
      building units (SBUs) have been constructed successfully. Compounds 2 and 3 are
      the second cases of cluster organic frameworks based on Lindqvist-type POM
      cluster SBUs. Furthermore, the cluster organic framework of 2 exhibits efficient
      electrocatalytic activity and strong durability in oxygen reduction reaction.

PMID- 30094993
TI  - Coupling of Carboxylic Acids with Ynamides and Subsequent Rearrangement for the
      Synthesis of Imides/Amides.
AB  - A coupling of carboxylic acids with ynamides and subsequent rearrangement for the
      synthesis of imides and amides is reported. The carboxylic acids could couple
      with ynamides to form alpha-acyloxyenamide followed by sulfonyl group migration
      and Mumm rearrangement to furnish the amides. Additionally, the products could be
      subjected to further rearrangement to deliver beta-keto amides. This metal-free
      process represents an interesting method for chemical bonds cleavage and
      regeneration. Furthermore, divergent transformation of products were conducted to
      deliver an array of compounds.

PMID- 30094994
TI  - A Cloud-Based Metabolite and Chemical Prioritization System for the
      Biology/Disease-Driven Human Proteome Project.
AB  - Targeted metabolomics and biochemical studies complement the ongoing
      investigations led by the Human Proteome Organization (HUPO) Biology/Disease
      Driven Human Proteome Project (B/D-HPP). However, it is challenging to identify
      and prioritize metabolite and chemical targets. Literature-mining-based
      approaches have been proposed for target proteomics studies, but text mining
      methods for metabolite and chemical prioritization are hindered by a large number
      of synonyms and nonstandardized names of each entity. In this study, we developed
      a cloud-based literature mining and summarization platform that maps metabolites
      and chemicals in the literature to unique identifiers and summarizes the
      copublication trends of metabolites/chemicals and B/D-HPP topics using Protein
      Universal Reference Publication-Originated Search Engine (PURPOSE) scores. We
      successfully prioritized metabolites and chemicals associated with the B/D-HPP
      targeted fields and validated the results by checking against expert-curated
      associations and enrichment analyses. Compared with existing algorithms, our
      system achieved better precision and recall in retrieving chemicals related to
      B/D-HPP focused areas. Our cloud-based platform enables queries on all biological
      terms in multiple species, which will contribute to B/D-HPP and targeted
      metabolomics/chemical studies.

PMID- 30094996
TI  - Risperidone and Intracranial Hypertension: A Case Report and Literature Review.

PMID- 30094997
TI  - Cancer is not associated with higher short or long-term mortality after
      successful resuscitation from out-of-hospital cardiac arrest when adjusting for
      prognostic factors.
AB  - OBJECTIVE: As the prevalence of malignancies in the general population increases,
      the odds of an out-of-hospital cardiac arrest (OHCA) patient having a history of
      cancer likewise increases, and the impact on post-cardiac arrest care and
      mortality is not well known. We aimed to investigate 30-day and 1-year mortality
      after successful resuscitation in patients with cancer prior to OHCA compared
      with OHCA patients without a previous cancer diagnosis. METHODS: A cohort of 993
      consecutive OHCA patients with successful resuscitation during 2007-2011 was
      included. Vital status was obtained from the Danish Civil Register, and cancer
      diagnoses from the Danish National Patient Register dating back to 1994. Primary
      endpoints were 30-day, 1-year and long-term mortality (no cancer: mean 811 days;
      cancer: mean 406 days), analysed by Cox regression. Functional status assessed by
      cerebral performance category at discharge and use of post-resuscitation care
      were secondary endpoints. RESULTS: A total of 119 patients (12%) were diagnosed
      with cancer prior to OHCA. Mortality was higher in patients with cancer (30-day
      69% vs. 58%, P=0.01); however, after adjustment for prognostic factors cancer was
      no longer associated with higher mortality (hazard ratio (HR)30 days 0.98, 95%
      confidence interval (CI) 0.76-1.27, P=0.88; HR1 year 0.99, 95% CI 0.78-1.27,
      P=0.96 HRend of follow-up 0.95, 95% CI 0.75-1.20, P=0.67). Favourable cerebral
      performance category scores in patients alive at discharge did not differ
      (cerebral performance category 1 or 2 n=310 (84%) vs. n=31 (84%), P=1).
      CONCLUSION: Cancer prior to OHCA was not associated with higher mortality in
      patients successfully resuscitated from OHCA when adjusting for confounders.
      Cancer prior to OHCA should be used with caution when performing prognostication
      after OHCA.

PMID- 30094995
TI  - DNA-Corralled Nanodiscs for the Structural and Functional Characterization of
      Membrane Proteins and Viral Entry.
AB  - Here we present a modular method for manufacturing large-sized nanodiscs using
      DNA-origami barrels as scaffolding corrals. Large-sized nanodiscs can be produced
      by first decorating the inside of DNA barrels with small lipid-bilayer nanodiscs,
      which open up when adding extra lipid to form large nanodiscs of diameters ~45 or
      ~70 nm as prescribed by the enclosing barrel dimension. Densely packed membrane
      protein arrays are then reconstituted within these large nanodiscs for potential
      structure determination. Furthermore, we demonstrate the potential of these
      nanodiscs as model membranes to study poliovirus entry.

PMID- 30094998
TI  - A Correlational Study of Acute Stress and Resilience Among Hospitalized Burn
      Victims Following the Taiwan Formosa Fun Coast Explosion.
AB  - Although the survival rate of burn patients in the Formosa Fun Coast Explosion
      disaster increased significantly, for patients facing long-term rehabilitation,
      there remained great stress. Therefore, the aim of this study was to explore the
      predictors of resilience among burn patients in this major disaster. We conducted
      a cross-sectional, descriptive study in a medical center in northern Taiwan, with
      a total of 30 burn patients enrolled. Patients' demographics were collected, and
      the Resilience Scale and Perceived Stress Scale were administered. Multivariate
      statistical analysis by stepwise and linear regression was used to test these
      predictors of resilience. The results showed that perceived stress was the key
      predictor of resilience in the stepwise regression analysis and by adjusting
      variables including stress level, gender, and education level. These results
      indicate that the stress level of burn patients should be determined first to
      provide more targeted methods for reducing stress and improving resilience.

PMID- 30094999
TI  - Evaluation of Neonates With Suspected Congenital Heart Disease: A New Cost
      Effective Algorithm.
AB  - We assessed the value of existing guidelines for the evaluation of suspected
      congenital heart disease (CHD) in term neonates and propose a revised algorithm.
      Retrospective chart review of newborns referred for cardiac evaluation at a
      tertiary care center was performed. A total of 777 newborns qualified for the
      study. Among these, 3 critical and 8 major CHD were identified. The sensitivity
      of the combination of abnormal physical examination and pulse oximetry screening
      for major and critical CHD was 100%. The cost to detect a case of critical CHD,
      based on echocardiograms done for all abnormal electrocardiograms, was 3.4 times
      more than that incurred for performing this test on the basis of abnormal pulse
      oximetry and physical examination. Adding electrocardiogram to CHD screening
      increases cost without adding diagnostic yield. Based on our findings, we propose
      a revised algorithm for a systematic cost-effective approach to cardiac
      evaluation of term newborns with suspected CHD.

PMID- 30095000
TI  - The Very Efficient Assessment of Need for Cognition: Developing a Six-Item
      Version.
AB  - The need for cognition refers to people's tendency to engage in and enjoy
      thinking and has become influential across social and medical sciences. Using
      three samples from the United States and the United Kingdom ( N = 1,596), we
      introduce a six-item short version of the Need for Cognition Scale (NCS-18).
      First, we reduced the number of items from 18 to 6 based on the items'
      discrimination values, threshold levels, measurement precision (item information
      curve), item-total correlations, and factor loadings. Second, we confirmed the
      one-factor structure and established measurement invariance across countries and
      gender. Finally, we demonstrated that while the NCS-6 provides significant time
      savings, it comes at a minimal cost in terms of its construct validity with
      external variables such as openness, cognitive reflection test, and need for
      affect. Overall, our findings indicate that the NCS-6 is a parsimonious,
      reliable, and valid measure of need for cognition.

PMID- 30095001
TI  - Comparison of Clinical Presentation and Surgical Outcomes Between Recurrent Acute
      Rhinosinusitis and Chronic Rhinosinusitis.
AB  - INTRODUCTION: The authors assessed clinical presentations and anatomic variants
      among patients with recurrent acute rhinosinusitis (RARS), chronic rhinosinusitis
      (CRS) without nasal polyps (CRSsNP), and CRS with nasal polyps (CRSwNP).
      Additionally, differences in the postoperative improvement of each category were
      evaluated. METHODS: The authors performed an analysis of 304 patients who
      underwent endoscopic sinus surgery. They were divided into groups with RARS,
      CRSsNP, and CRSwNP. Patients had to complete the Sino-Nasal Outcome Test (SNOT
      20) on surgery 1 day before and 6 months after surgery. Patient demographics and
      comorbidities were reviewed. We reviewed all patients' computed tomographic
      findings to analyze anatomic variants. RESULTS: No significant differences were
      found among the average preoperative SNOT-20 scores of the 3 groups. Patients
      with RARS were significantly more likely to show agger nasi cells, Haller cells,
      and septal deviation on computed tomography. Those with CRSwNP had significantly
      smaller mean infundibular widths. All groups showed significantly improved SNOT
      20 scores postoperatively. CONCLUSION: The different anatomic variants found
      among patients with RARS, CRSsNP, and CRSwNP can facilitate surgical prognostic
      evaluation.

PMID- 30095003
TI  - The Impact of Tissue Storage Conditions on Rat Olfactory Ensheathing Cell Yield
      and the Future Clinical Implications.
AB  - Trauma causes spinal cord injury, and the devastating consequences of the injury
      are due to the failure of the damaged central nervous system (CNS) axons to
      regenerate. Previous studies have shown that olfactory ensheathing cells (OECs)
      are a unique type of glial cell and they can promote regeneration of CNS axons to
      aid recovery after spinal cord injury. Transplantation of OECs, in particular
      from the olfactory bulb (OB), is considered one of the most promising therapeutic
      strategies for the repair of CNS injuries, including spinal cord injury.
      Transplantation of OECs can be autologous or allogenic. Here we focused on the
      less invasive and more error-proof allograft approach which needs a collection of
      donor OB tissue for OEC production. In this study, we investigated the effects on
      the yield and proportions of OECs and olfactory nerve fibroblasts (ONFs) from
      storing OB tissue in various media for periods of 24 and 48 hours. The OEC yield
      contributes to the viability of a successful cell transplant. We concluded that
      storing OB tissue for a period longer than 24 hours negatively impacted the total
      cell number and subsequently the OEC population. This study provides useful
      information for future clinical applications.

PMID- 30095005
TI  - Poststreptococcal Glomerulonephritis and Antibiotics: A Fresh Look at Old Data.

PMID- 30095002
TI  - Preconditioning Enhances the Therapeutic Effects of Mesenchymal Stem Cells on
      Colitis Through PGE2-Mediated T-Cell Modulation.
AB  - Mesenchymal stem cell (MSC)-based cell therapy has been demonstrated as a
      promising strategy in the treatment of inflammatory bowel disease (IBD), which is
      considered an immune disease. While the exact mechanisms underlying the
      therapeutic effect of MSCs are still unclear, MSCs display anti-inflammatory and
      immunomodulatory effects by interacting with various immunoregulatory cells. Our
      previous studies have shown that MSCs can be preconditioned and deconditioned
      with enhanced cell survival, differentiation and migration. In this study, we
      evaluated the effect of preconditioning on the immunoregulatory function of human
      umbilical cord-derived MSCs (hUCMSCs) and their therapeutic effect on treating
      IBD. Our results show that intraperitoneal administration of deconditioned
      hUCMSCs (De-hUCMSCs) reduces the disease activity index (DAI), histological
      colitis score and destruction of the epithelial barrier, and increases the body
      weight recovery more intensively than that of un-manipulated hUCMSCs. In
      addition, De-hUCMSCs but not hUCMSCs elicit anti-apoptotic effects via induction
      of the ERK pathway during the early stage of IBD development. In vitro co-culture
      studies indicate that De-hUCMSCs suppress T-cell proliferation and activation
      more markedly than hUCMSCs. Moreover, De-hUCMSCs block the induction of
      inflammatory cytokines such as tumor necrosis factor (TNF)alpha and interleukin
      (IL)-2, while promoting the secretion of the anti-inflammatory cytokine IL-10 in
      T-cells. Mechanically, we find that prostaglandin E2 (PGE2) secretion is
      significantly increased in De-hUCMSCs, the suppression of which dramatically
      abrogates the inhibitory effect of De-hUCMSCs on T-cell activation, implying that
      the crosstalk between De-hUCMSCs and T-cells is mediated by PGE2. Together, we
      have demonstrated that preconditioning enhances the immunosuppressive and
      therapeutic effects of hUCMSCs on treating IBD via increased secretion of PGE2.

PMID- 30095006
TI  - Analysis of "Use of Blood Glucose Meters Featuring Color Range Indicators
      Improves Glycemic Control and Patients With Diabetes in Comparison to Blood
      Glucose Meters Without Color (ACCENTS Study)".
AB  - Self-monitoring of blood glucose is a part of integral care of patients with
      diabetes mellitus. Understanding and appropriately responding to glucose levels
      is a fundamental part of self-management. Grady et al's work, published in the
      current issue of Journal of Diabetes Science and Technology, investigated whether
      switching people with diabetes from their usual meter to a meter featuring color
      range indicator (CRI) could improve glycemic control, by facilitating improved
      understanding of blood glucose targets. In this small but well-designed study,
      the authors have shown that meters with CRI features offer a potential advantage
      and may improve glucose control in patients with diabetes, both with T1D and T2D,
      across the therapy spectrum from oral agents to insulin therapy.

PMID- 30095004
TI  - An Ex Vivo Vessel Injury Model to Study Remodeling.
AB  - OBJECTIVE: Invasive coronary interventions can fail due to intimal hyperplasia
      and restenosis. Endothelial cell (EC) seeding to the vessel lumen, accelerating
      re-endothelialization, or local release of mTOR pathway inhibitors have helped
      reduce intimal hyperplasia after vessel injury. While animal models are powerful
      tools, they are complex and expensive, and not always reflective of human
      physiology. Therefore, we developed an in vitro 3D vascular model validating
      previous in vivo animal models and utilizing isolated human arteries to study
      vascular remodeling after injury. APPROACH: We utilized a bioreactor that enables
      the control of intramural pressure and shear stress in vessel conduits to
      investigate the vascular response in both rat and human arteries to intraluminal
      injury. RESULTS: Culturing rat aorta segments in vitro, we show that vigorous
      removal of luminal ECs results in vessel injury, causing medial proliferation by
      Day-4 and neointima formation, with the observation of SCA1+ cells (stem cell
      antigen-1) in the intima by Day-7, in the absence of flow. Conversely, when
      endothelial-denuded rat aortae and human umbilical arteries were subjected to
      arterial shear stress, pre-seeding with human umbilical ECs decreased the number
      and proliferation of smooth muscle cell (SMC) significantly in the media of both
      rat and human vessels. CONCLUSION: Our bioreactor system provides a novel
      platform for correlating ex vivo findings with vascular outcomes in vivo. The
      present in vitro human arterial injury model can be helpful in the study of EC
      SMC interactions and vascular remodeling, by allowing for the separation of
      mechanical, cellular, and soluble factors.

PMID- 30095007
TI  - Identifiability Analysis of Three Control-Oriented Models for Use in Artificial
      Pancreas Systems.
AB  - OBJECTIVE: Our aim is to analyze the identifiability of three commonly used
      control-oriented models for glucose control in patients with type 1 diabetes
      (T1D). METHODS: Structural and practical identifiability analysis were performed
      on three published control-oriented models for glucose control in patients with
      type 1 diabetes (T1D): the subcutaneous oral glucose minimal model (SOGMM), the
      intensive control insulin-nutrition-glucose (ICING) model, and the minimal model
      control-oriented (MMC). Structural identifiability was addressed with a
      combination of the generating series (GS) approach and identifiability tableaus
      whereas practical identifiability was studied by means of (1) global ranking of
      parameters via sensitivity analysis together with the Latin hypercube sampling
      method (LHS) and (2) collinearity analysis among parameters. For practical
      identifiability and model identification, continuous glucose monitor (CGM),
      insulin pump, and meal records were selected from a set of patients (n = 5) on
      continuous subcutaneous insulin infusion (CSII) that underwent a clinical trial
      in an outpatient setting. The performance of the identified models was analyzed
      by means of the root mean square (RMS) criterion. RESULTS: A reliable set of
      identifiable parameters was found for every studied model after analyzing the
      possible identifiability issues of the original parameter sets. According to an
      importance factor ([Formula: see text]), it was shown that insulin sensitivity is
      not the most influential parameter from the dynamical point of view, that is, is
      not the parameter impacting the outputs the most of the three models, contrary to
      what is assumed in the literature. For the test data, the models demonstrated
      similar performance with most RMS values around 20 mg/dl (min: 15.64 mg/dl, max:
      51.32 mg/dl). However, MMC failed to identify the model for patient 4. Also,
      considering the three models, the MMC model showed the higher parameter
      variability when reidentified every 6 hours. CONCLUSION: This study shows that
      both structural and practical identifiability analysis need to be considered
      prior to the model identification/individualization in patients with T1D. It was
      shown that all the studied models are able to represent the CGM data, yet their
      usefulness in a hypothetical artificial pancreas could be a matter of debate. In
      spite that the three models do not capture all the dynamics and metabolic effects
      as a maximal model (ie, our FDA-accepted UVa/Padova simulator), SOGMM and ICING
      appear to be more appealing than MMC regarding both the performance and parameter
      variability after reidentification. Although the model predictions of ICING are
      comparable to the ones of the SOGMM model, the large parameter set makes the
      model prone to overfitting if all parameters are identified. Moreover, the
      existence of a high nonlinear function like [Formula: see text] prevents the use
      of tools from the linear systems theory.

PMID- 30095008
TI  - Family Functioning in Pediatric Primary Care Patients.
AB  - INTRODUCTION: The purpose of this study was to pilot a brief measure of family
      functioning (Family Assessment Device-General Functioning [FAD_GF]) with
      caregivers of children aged 2 to 18 years, seen for routine pediatric primary
      care visits. METHODS: This study evaluated the psychometric properties of the
      FAD_GF in a pediatric primary care sample of 400 families. Confirmatory factor
      analysis was used to validate the FAD_GF using R, and WLSMV was used to estimate
      missing variables. RESULTS: The FAD_GF was found to be reliable with this sample,
      alpha = .90. The model fit was chi2(54) = 56.44, P = .38, with root mean square
      error of approximation = .01 and comparative fit index = .99. The 12 items were
      significantly predicted by family functioning, and family functioning explained
      more than 20% of the variance in the items, R2 > .25. Overall, 12.6% (n = 46) of
      families were identified as having clinically impaired family functioning.
      DISCUSSION: The FAD_GF provides clinicians the ability to make evidence-informed
      decisions regarding referrals to family therapists.

PMID- 30095009
TI  - Novel small self-assembled resveratrol-bearing cubosomes and hexosomes:
      preparation, charachterization, and ex vivo permeation.
AB  - The study aims to elaborate novel self-assembled liquid crystalline nanoparticles
      (LCNPs) of resveratrol which has neuro-protective, anti-aging, and anticancer
      activity. Resveratrol loaded LCNPs fabrication and optimization for transdermal
      delivery was assessed via a quality by design approach based on 23 full factorial
      designs. The cubic phase of LCNPs was successfully prepared using GMO (glyceryl
      monooleate) via the emulsification technique. Based on the factorial design, the
      independent operating variables significantly affected the five dependent
      responses. The cubosomes and hexosomes hydrodynamic diameters were in the
      nanometer range (135-256 nm) with narrow particle size distribution, high
      negative zeta potential >= -27.9 mV, and entrapment efficiency >=73.5%. The LCNPs
      succeeded in sustaining resveratrol release for almost 24 h, following a non
      fickian transport of drug diffusion mechanism. Ex-vivo study revealed a
      significant enhancement up to six folds in the transdermal permeation of
      resveratrol-loaded LCNPs compared to its suspension. The selected LCNPs exhibited
      a high physical stability while retaining the cubic structure for at least 3
      months. Quality by design approach successfully accomplished a predictable
      mathematical model permitting the development of novel LCNPs for sustained
      transdermal delivery of resveratrol.

PMID- 30095010
TI  - Pharmacotherapeutic approaches for transportation of anticancer agents via skin.
AB  - Cancer is the largest family of diseases that involve abnormal uncontrolled cell
      growth which metastasizes to other parts of the body. The most common type of
      cancers includes lung, liver, colorectal, prostate, stomach, breast and cervical
      cancer with skin cancer excluding melanoma (contribute up to 40% of the cases).
      The conventional treatment approaches like surgery, chemotherapy, etc., have
      several side effects such as severe inflammation and pain. Hence,
      pharmacotherapeutic approaches of antineoplastic agents can be advantageous for
      treating various forms of cancer through the skin. Novel transdermal techniques
      and preparations have been emerged to overcome the limitations of skin and to
      penetrate inside the cancerous cells by transporting through the deeper tissues
      of the skin. The transdermal penetration of drugs using different formulations
      such as nanocarriers, physical penetration enhancement techniques, chemical
      penetration enhancers and newer technologies such as gels, dendrimers, needle
      free injection jet etc., show improved patient compliance, abolition of scars and
      economic value. The topical delivery of antineoplastic agents is an attractive
      choice for increasing site-specific delivery, reducing side effects and improving
      therapeutic effects. The objective of this review is to present insights into
      pharmacotherapeutic techniques, which can be used for transdermal delivery of
      anticancer agents through skin due to its potential to create a new frontier in
      treatment of cancer.

PMID- 30095011
TI  - Young People Under Youth Justice Supervision With Varying Child Protection
      Histories: An Analysis of Group Differences.
AB  - There is now convincing evidence that childhood maltreatment is associated with
      youth offending; however, relatively little is known about the characteristics
      and needs of those who are involved in both the child protection and youth
      justice systems, and the extent to which these might differ according to level of
      child protection involvement. This study reports the characteristics and needs of
      2,045 young people who were under supervision in secure custody or detention in
      South Australia between 1995 and 2012 according to the level of exposure to the
      child protection system in an Australian jurisdiction. Five groups of young
      offenders were compared: (a) no known child protection notifications or
      substantiated experience of abuse and/or neglect, (b) notifications only, (c)
      substantiated notifications, (d) notifications or substantiations and subsequent
      placement in out-of-home care (OHC), and (e) placement in OHC only. The results
      indicate that young people who have a history of child protection system
      involvement have significantly greater and more complex needs than those who have
      no child protection experience. It is concluded that different service responses
      may be required to meet the diverse needs of these groups of young people under
      youth justice supervision.

PMID- 30095012
TI  - Modified PAMAM vehicles for effective TRAIL gene delivery to colon
      adenocarcinoma: in vitro and in vivo evaluation.
AB  - TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) gene therapy is
      considered as one of the promising approaches for cancer treatment.
      Polyamidoamine (PAMAM) is one of the most extensively applied polymeric vector in
      gene delivery. In the current study, PAMAM (G4 and G5) dendrimers were modified
      with alkyl-carboxylate chain, PEG and cholesteryl chloroformate in order to
      enhance transfection efficiency through overcoming extracellular and
      intracellular barriers while reducing PAMAM cytotoxicity. Gene delivery
      efficiency of synthetized vectors was evaluated by both GFP (green fluorescent
      protein) reporter gene and TRAIL plasmid in colon cancer cells, in vitro and in
      vivo. The obtained results demonstrated that PAMAM G4-alkyl-PEG (3%)-Chol (5%)
      TRAIL complexes at C/P ratio 4 could significantly increase cell death (29.45%)
      in comparison with unmodified PAMAM vector (15.5%). Moreover, in vivo study in
      C26 tumor-bearing BALB/c mice suggested that the prepared non-toxic safe vector
      could inhibit the tumor growth. This study represented the potent vehicle based
      on cholesterol-grafted PAMAM dendrimers with alkyl-PEG modification for efficient
      gene delivery in vitro and in vivo.

PMID- 30095013
TI  - Sexual Violence-Related Pregnancy Among Internally Displaced Women in an
      Internally Displaced Persons Camp in Northeast Nigeria.
AB  - Sexual violence is quite common in conflict situations and puts women at risk of
      unintended pregnancies. In the northeast region of Nigeria with the ongoing
      insurgency, a substantial number of women are kidnapped and subjected to forced
      marriages and repeated sexual assaults. This study set out to report on the
      disclosure and outcomes of sexual violence-related pregnancies (SVRPs) among
      women liberated from insurgents and relocated to one of largest Internally
      Displaced Persons (IDP) camps located in Borno State, northeast Nigeria. The
      clinic records of women with SVRP were reviewed. Forty-seven women with SVRP were
      identified by the health care providers using a snowball technique to reach as
      many of the women with SVRP as possible. The mean age of the participants was
      15.3 years ( SD = 3.4 years), and all the participants had spent 2 years or more
      in captivity. Most of the women first disclosed the pregnancy to their peers
      before disclosure to health care providers or family members. All the women
      initially requested to have the pregnancy terminated; however, abortion services
      are not offered in the clinic in line with the country's restrictive abortion
      laws. Following counseling and psychosocial support offered in the clinic, 19
      (40%) of the women continued with the pregnancy and were delivered in the camp
      clinic while the remaining 26 women left the camp shortly after disclosure and
      pregnancy outcomes are not known. SVRP is not uncommon in humanitarian settings
      with its associated stigma and unwillingness among the survivors to keep the
      pregnancy. There is a need for further studies to provide more insight into the
      extent of this problem and help-seeking for SVRPs especially for women in such
      difficult circumstances to provide needed empirical information to drive advocacy
      efforts for more comprehensive services.

PMID- 30095014
TI  - Early Correction of Distal Radius Partial Articular Malunion Leads to Good Long
      term Functional Recovery at Mean Follow-up of 4 Years.
AB  - BACKGROUND: Distal radius articular step-off or deformity may cause posttraumatic
      arthritis and poor functional outcome. The purpose of this study was to evaluate
      pain and functional outcomes in patients with malunited partial articular distal
      radius fractures who underwent corrective osteotomy. We hypothesized that
      anatomic restoration of distal radius articular surface after a malunited partial
      articular distal radius fracture results in improvement in pain and functional
      measures and delays the development of posttraumatic arthritis. METHODS: Seven
      consecutive patients with mean age of 38 years underwent corrective osteotomy via
      either a standard dorsal approach or combined dorsal and volar approach. Mean
      time from injury to corrective osteotomy was 10 weeks. Patients were assessed
      with respect to Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH),
      forearm and wrist range of motion, pain, and grip strength. RESULTS: At mean
      follow-up of 44 months, significant improvements in pain scores (7.1-0.9, P <
      .001), QuickDASH (38.7-11.6, P < .001), grip strength (21.4-30.0 kg, P = .01)
      were achieved. All range of motion measurements demonstrated significant
      improvements except forearm pronation. One patient demonstrated radiographic
      evidence of osteoarthritis but had no pain at final follow-up. No patients
      required secondary surgery for removal of symptomatic hardware. CONCLUSIONS:
      Based on these findings, we recommend that early corrective osteotomies should be
      considered in young patients with intra-articular distal radius malunions before
      considering salvage procedures such as partial or complete wrist arthrodesis.

PMID- 30095015
TI  - Comorbidity of Migraine and Epilepsy in Pediatrics: A Review.
AB  - Migraine and epilepsy are classified as chronic paroxysmal neurologic disorders
      sharing many clinical features, as well as possible treatment options. This
      review highlights the similarities between migraine and epilepsy in pediatrics,
      focusing on epidemiologic, pathophysiological, genetic, clinical, and
      pharmacologic aspects. Despite the fact that several syndromes share symptoms of
      both migraine and epilepsy, further research is needed to clarify the
      pathophysiological and genetic basis of their comorbidity. Drugs used for
      prophylactic therapy of migraine and epilepsy have similar pharmacologic
      properties. The role of epileptic pharmacotherapy in the prophylaxis of migraine
      is assessed, including the use of conventional antiepileptic drugs, calcium
      channel blockers, and nonpharmacologic methods such as dietary therapy,
      supplements, and vagal nerve stimulation. Further randomized, controlled clinical
      trials assessing pharmacologic and nonpharmacologic methods for the treatment of
      both disorders are essential, in order to initiate new therapeutic approaches.

PMID- 30095017
TI  - Missed Opportunities to Address Pregnancy Prevention With Young Men in Primary
      Care.
AB  - Young men (aged 15-24 years) have pregnancy prevention needs, yet little is known
      about whether they perceive they learn about pregnancy prevention in primary
      care. A sample of 190 young men seen in primary care in one city from April 2014
      to September 2016 were assessed on perceived learning about pregnancy prevention,
      background and visit characteristics, pregnancy prevention care receipt, and
      contraception needs at last sex. The majority of participants were non-Hispanic
      black (92%), aged 15 to 19 years (54%), seen for a physical examination (52%),
      and established patients (87%). Few participants perceived they learned about
      pregnancy prevention (32%), regardless of sexual activity (33% among sexually
      active participants, 26% among never sexually active). Poisson regression models
      determined that perceived learning about pregnancy prevention was independently
      associated with young men's pregnancy prevention care receipt and contraception
      needs at last sex. Findings highlight the need to improve providers' delivery of
      pregnancy prevention services to young men.

PMID- 30095016
TI  - Consumers' Perceptions About Pharmaceutical Care Provided by Community
      Pharmacists in China in Relation to Over-the-Counter Drugs: A Qualitative Study.
AB  - While patient-centered care is highly anticipated nowadays, investigation of
      consumers' perceptions and expectations about pharmacist's pharmaceutical care
      when providing over-the-counter (OTC) drugs is sparse. This article aimed to
      explore consumers' perceptions regarding the pharmaceutical care that community
      pharmacists provide in relation to OTC drugs. Semistructured interviews were
      conducted with consumers recruited (N = 97) in Yinchuan City, China. The 4 main
      themes that emerged were expectations on pharmaceutical care, attitude toward
      pharmacist's competence, experience of self-medication, and suggestions for
      improving pharmaceutical care. Most participants had high expectations on
      community pharmacists to recommend the right medicines, to advise them about the
      effective use of drug, to advise them about the safe use of drug, and to
      recommend economic drugs. However, their previous experiences at community
      pharmacy were far from satisfaction reportedly, leading to a general distrust in
      pharmacist's certification and qualification, knowledge, communication skills,
      and attitude. As a result, the participants turned to self-medication based on
      their personal experiences, their relatives' experiences, the information on drug
      label, and the information distributed in the mass media. Realizing the need to
      improve pharmaceutical care, the participants also made improvement suggestions
      specific to community pharmacist, community pharmacy, and the government.

PMID- 30095018
TI  - Endoscopic trans-nasal repair of basal encephalocele associated with morning
      glory syndrome.

PMID- 30095019
TI  - Upper gastrointestinal bleeding in critically ill patients: proton-pump
      inhibitors, histamine-2 receptor antagonists or placebo? Many questions remain
      unanswered.

PMID- 30095020
TI  - Modification of alpha-lactose monohydrate as a direct compression excipient using
      roller compaction.
AB  - Roller compaction was used to prepare a direct-compressed lactose excipient using
      crystalline alpha-lactose monohydrate. The effect of various roller compaction
      process parameters (compaction pressure, compaction repetition, and speed ratio)
      on the characteristics of compacted alpha-lactose monohydrate was investigated.
      Results were compared with data obtained using industrial spray-dried lactose and
      lactose samples with different degrees of crystallinity. XRPD analysis revealed
      that roller compaction reduced the crystallinity of alpha-lactose monohydrate,
      and the resulting material is similar to spray-dried lactose in behavior as a
      direct compression excipient. Roller compaction introduced desirable
      characteristics to the raw alpha-lactose monohydrate by inducing changes in
      crystallinity and particle morphology. Scanning electron microscopy results
      indicated that the compaction process converted some of the original torpedo
      shaped crystals of alpha-lactose monohydrate into a more cylindrical shape with
      rounded edges. Compaction pressure and repetition of compaction have a
      significant effect on the modification of the crystallinity of the processed, raw
      alpha-lactose monohydrate.

PMID- 30095021
TI  - Multifocal lumbar disc herniation at a single level: a potential pitfall for
      wrong side surgery.

PMID- 30095022
TI  - The effect of vitamin D2 supplementation on muscle strength in early
      postmenopausal women: a randomized, double-blind, placebo-controlled trial.
AB  - BACKGROUND: Low serum 25-hydroxyvitamin D [25(OH)D] has been shown to be
      associated with low muscle mass and loss of muscle strength, resulting in
      increased disability and frailty in older men and women. Vitamin D deficiency is
      common in postmenopausal women. The primary objective of the present study was to
      evaluate the effects of vitamin D supplementation on muscle strength in early
      postmenopausal women. The effects of vitamin D2 supplementation on muscle mass
      and muscle cross-sectional area (CSA) were secondarily investigated. METHODS: A
      12-week, prospective, randomized, double-blind, placebo-controlled trial was
      conducted in early postmenopausal women (45-60 years old) with vitamin D
      deficiency (serum 25(OH)D < 20 ng/ml). A total of 88 subjects were randomized
      into group I: vitamin D2 supplement 40 000 IU/week (n = 44), or group II: placebo
      (n = 44). Serum 25(OH)D level, muscle strength, muscle mass and muscle CSA were
      assessed at baseline and 12 weeks after the supplementation. RESULTS: After 12
      weeks of supplementation, 70% of women in group I achieved a sufficient level of
      serum 25(OH)D (>30 ng/ml). There were significant differences in changes of serum
      25(OH)D levels between the two groups (p < 0.05). Muscle strength and muscle CSA
      in group I increased significantly after 12 weeks (p = 0.015, 0.045,
      respectively). However, there were no significant differences in the mean changes
      of muscle strength, muscle mass and muscle CSA between the two groups (p = 0.16,
      0.89, 0.84, respectively). CONCLUSION: In this study, we found no obvious effect
      of vitamin D supplementation on the changes in muscle strength, muscle mass and
      muscle CSA when compared to placebo. However, there were significant changes in
      muscle strength and muscle CSA from baseline in the vitamin D supplementation
      group.

PMID- 30095023
TI  - Quantifying the economic impact of a digital self-care behavioral health platform
      on Missouri Medicaid expenditures.
AB  - AIM: The primary objective of this study is to estimate the economic benefits
      relative to return on investment (ROI) of a state-wide initiative to integrate
      digital behavioral health (BH) self-care into the community BH system. METHODS:
      The observational study reviewed claims data of 799 people who registered with
      the digital tool (myStrength) and 715 matched control study participants. The
      control group was formed via coarsened exact match with blocking variables,
      including presence on the claims file, volume of health care utilization,
      participation in a medical health home, BH diagnosis and volume of psychotherapy
      claims. The primary study analysis of cost differences for the BH self-care tool
      group versus the control group were calculated by cost setting and the ROI of the
      BH self-care tool was estimated. Cost settings assessed include inpatient,
      emergency services, general and psychiatric outpatient, and outpatient
      psychotherapy. RESULTS: An incremental annual difference in difference reduction
      of $382 per user was observed over the 11 month study period in the self-care
      tool group. Sensitivity analysis indicated an ROI of between 142% and 695%.
      CONCLUSIONS: Augmenting BH offerings to include digital BH self-care tools
      appears to generate positive ROI via reduced total cost of care.

PMID- 30095024
TI  - Self-Reported Lifetime Violence Exposure and Self-Compassion Associated With
      Satisfaction of Life in Historically Black College and University Students.
AB  - In the United States, approximately 25% of minors have witnessed a violent act,
      specifically physical assault. African Americans from under-served backgrounds
      are more likely than other racial and ethnic groups to be exposed to traumatic
      events. However, there is scant literature examining violence exposure, SC, and
      life satisfaction collectively, specifically in an African American college
      sample. The current study sought to determine the associations among violence
      exposure, SC components, and life satisfaction in an African American college
      sample. The current sample was comprised of 356 participants (80% female) with a
      mean age of 20.23 (SD = 1.70). Eighty-eight participants (25%) reported being
      exposed to violence in their lifetime. Employing logistic regression, we
      determined violence exposed individuals were less likely to report high
      satisfaction of life than their non-exposed counterparts (OR = 0.58, 95% CIs =
      0.33, 1.00). Individuals with high level of self-kindness were approximately two
      times more likely to have higher satisfaction of life (OR = 2.48; CI = 1.52,
      4.05) compared to their low level self-kindness counterparts and in the presence
      of demographic covariates. These findings may educate and increase awareness of
      the impacts of traumatic events. This education could lead to the implementation
      of interventions to build upon overall well-being in order increase life
      satisfaction in college students.

PMID- 30095025
TI  - Antiplanktonic, antibiofilm, antiswarming motility and antiquorum sensing
      activities of green synthesized Ag-TiO2, TiO2-Ag, Ag-Cu and Cu-Ag nanocomposites
      against multi-drug-resistant bacteria.
AB  - Fighting of current antibiotics against multidrug-resistant (MDR) bacteria has
      not been completely successful. In this study, the bio-synthesized Ag-TiO2, TiO2
      Ag, Ag-Cu and Cu-Ag nanocomposites (NCs) were used against MDR bacteria including
      Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 (gram negative)
      and Staphylococcus aureus ATCC 43300 (gram positive). Antiplanktonic,
      antibiofilm, antiswarming motility and antiquorum sensing activities of these
      four NCs were measured by assays of agar well diffusion, minimum
      inhibition/minimum bactericidal concentrations (MIC/MBC), biofilm formation,
      biofilm morphology and pyocyanin amounts. Agar well diffusion method illustrated
      higher inhibition zone diameter (IZD) of Ag-TiO2 NCs with 13 +/- 1, 16 +/- 1.73
      and 21.66 +/- 1.52 mm against E. coli ATCC 25922, S. aureus ATCC 43300 and P.
      aeruginosa ATCC 27853 respectively. Swarming motility of P. aeruginosa at
      presence of NCs demonstrated lower density than control samples. Ordering of
      antibiofilm strength for these NCs was Ag-TiO2 > TiO2-Ag > Cu-Ag > Ag-Cu. In
      addition, biofilm roughness and also pyocyanin synthesis as virulence factor
      related to quorum sensing mechanisms of P. aeruginosa ATCC 27853 was decreased
      under Ag-TiO2 NCs. In total, the present investigation illustrated eco-friendly
      and one-pot way to synthesize metal NCs with having significant antibacterial,
      antibiofilm and antiquorum sensing abilities.

PMID- 30095026
TI  - Effect of exogenous p51a gene on the growth and chemo sensitivity of human lung
      adenocarcinoma cell lines.
AB  - BACKGROUND: The dysfunction of p53-mediated apoptosis is the key to
      tumorigenesis, so most gene therapy programs concentrate on improving the
      expressing level of wild-type p53 in tumour cells. However, the p53 gene therapy
      has not yielded satisfactory results in tumours with normal p53 function. A new
      member of p53 gene family-p63, has provided new hopes. TAp63gamma (p51A)
      resembles p53 the most, thus it might become a new promising therapeutic gene of
      tumours. METHODS: We designed the primer pairs of p51A and amplified the p51A
      cDNA sequence from human skeletal muscle poly A + RNA to construct recombinant
      plasmid. It was then transfected into human lung adenocarcinoma cell lines A549
      and NCI-H1299. RT-PCR, Western blot, MTT, flow cytometry and colony formation
      assay were used to analyse the growth and chemosensitivity of tumour cells.
      RESULTS: The recombinant plasmid was constructed and transfected into tumour
      cells successfully. After transfection, p51A mRNA, P51A protein and P21 protein
      level raised significantly. Cell proliferation capacity and colony formation rate
      decreased while cell apoptosis rate and chemosensitivity to cisplatin and
      adriamycin increased significantly. CONCLUSIONS: Exogenous p51A gene can increase
      its expression in A549 and NCI-H1299 cells, suppress cell growth and induce cell
      apoptosis. Moreover, it can also cooperate with chemotherapy and reduce the dose
      and side-effect. p51A gene can suppress tumours in spite of p53 status and p21
      gene might be involved. It might become a new promising therapeutic gene of
      tumours, which will make up for the limitation of p53 gene therapy.

PMID- 30095027
TI  - Intimate Partner Homicides in the United States, 2003-2013: A Comparison of
      Immigrants and Nonimmigrant Victims.
AB  - Intimate partner homicide (IPH) is a significant public health issue that has
      negative consequences for families and communities. Evidence is needed to support
      heterogeneity among groups affected by IPHs. This study examined differences in
      characteristics of male-perpetrated and female-perpetrated killings of native
      born and foreign-born residents in the United States. We analyzed 2003-2013 IPH
      homicide data collected in 19 U.S. states by the National Violence Death
      Reporting System, Center for Disease Control and Prevention, comparing IPH cases
      where the victim was U.S.-born versus foreign-born. We examined characteristics
      associated with male-perpetrated female killings and female-perpetrated male
      killings. Among the total homicides ( n = 147,092), foreign-born victims were
      more likely than U.S.-born victims to be associated with intimate-partner
      violence-related deaths. Women were the victims in 77.4% of IPHs, with a greater
      proportion of women victims of IPHs being foreign-born than U.S.-born. Foreign
      born women killed by their partners were more likely than U.S.-born women to be
      young, married, and killed by a young partner who stabbed, strangled, or
      suffocated them. IPHs policies, prevention, and intervention efforts need
      collaborative efforts between victim services, mental health, and the legal
      system to identify and intervene with populations at risk. Culturally specific
      prevention and intervention strategies are needed to address risks of IPHs among
      diverse groups based on nativity and race/ethnicity.

PMID- 30095028
TI  - Generating a Core Set of Outcomes for Hospital-Based Violence Intervention
      Programs.
AB  - Hospital-based violence intervention programs (HVIPs) engage individuals who have
      experienced violent victimization in postmedical care programming, with the goal
      of reducing the incidence and impact of future injuries. Although there is some
      empirical support for HVIPs' impact on violence and crime-related outcomes,
      proper impact assessment is limited by a lack of systematized research on
      outcomes that relate to the proximal goals and activities of the programs
      themselves. To address this critical gap, we conducted a two-stage Delphi method
      to elicit and prioritize these outcomes using the wisdom and experience of those
      who are engaged in service delivery (i.e., HVIP community-based practitioners,
      program coordinators, and embedded researchers; N = 79). Through this process,
      respondents prioritized outcomes related to posttraumatic stress symptoms,
      beliefs about aggression, coping strategies, and emotional regulation, which have
      not been consistently measured using validated or standardized tools. Results
      suggest that, rather than limiting program outcomes to those related to repeat
      violent injury or criminality, hospital- and community-based violence prevention
      programs seek to improve and measure mental health and socioemotional outcomes as
      a benchmark for healing and recovery after a violent injury. Prioritization of
      these outcomes broadens the definition of recovery to include psychosocial health
      and well-being. In addition, inclusion of these outcomes in effectiveness studies
      will serve to bolster the relevance of findings, and provide support for
      continued development and refinement of HVIP practice.

PMID- 30095029
TI  - The Association of Depressive Symptoms and Intimate Partner Violence Against
      Women in Northwestern Botswana.
AB  - Although links between mental health and intimate partner violence (IPV) have
      been discussed extensively in the scholarly literature, little empirical data
      exist about these phenomena in Botswana. This study addressed this gap by
      examining the nature, extent, and risk factors associated with symptoms of major
      depressive disorders (MDD) using cross-sectional data collected in 2009-2010 in
      northwestern Botswana. A random sample of 469 women participated in
      semistructured interviews about their lives, health, and experiences with
      violence. Thirty-one percent of respondents were found to meet the symptom
      criteria for MDD. Factors associated with MDD included emotional or physical
      violence by an intimate partner and being in a relationship in which both
      partners consumed alcohol. One in five women reported a recent experience of
      emotional violence, while 37% of respondents reported recent physical IPV. Women
      who have experienced emotional or physical IPV in the last 12 months have 89% and
      82% greater odds, respectively, of having symptoms of MDD ( p < .05) than women
      who have not recently experienced either form of violence. Women in relationships
      in which both partners consumed alcohol had more than twice the odds of MDD
      compared with women in relationships where neither partner or only one partner
      drank. Given the significant association of violence, alcohol, and MDD, screening
      for all three conditions should be part of routine care in health care settings
      in Botswana. Interventions to reduce IPV and alcohol consumption may help
      alleviate the burden of MDD in women in this setting.

PMID- 30095030
TI  - Management and Anesthetic Considerations for Patients With Anomalous Aortic
      Origin of a Coronary Artery.
AB  - The term "coronary artery anomalies" encompasses a large and heterogeneous group
      of disorders that may affect origin, intrinsic anatomy, course, location, and
      termination of the coronary arteries. With these different anatomies,
      presentation, symptoms, and outcomes are heterogeneous as well. While significant
      efforts are directed toward improving diagnosis and risk-stratification, best
      evidence-guided practices remain in evolution. Data about anesthetic management
      of patients with coronary anomalies are lacking as well. This review aims to
      provide the anesthesiologist with a better understanding of an important subgroup
      of coronary artery anomalies: anomalous aortic origin of a coronary artery. We
      will discuss classification, pathophysiology, incidence, evaluation, management,
      and anesthetic implications of this potentially fatal disease group.

PMID- 30095031
TI  - Building a Grounded Theory of Engagement in Mindfulness-Based Group Therapy for
      Distressing Voices.
AB  - Mindfulness-based group therapy shows promise as a treatment for distressing
      voice hearing. However, fostering engagement in groups can be challenging, and no
      theory of engagement in group therapy for distressing voices exists to guide
      practice or research. This study employed Grounded Theory Method to build a
      theory of engagement in mindfulness-based groups for distressing voices. Ten
      service-users and three therapists were interviewed about their experiences of
      such groups. The model that emerged involves a recursive process of investing in
      change and continually evaluating its usefulness and safety. Barriers to
      engagement were often overcome, but sometimes compromised perceived safety,
      leading to dropout. For others, group participation led to rewards, some of which
      were integrated beyond group termination. Group engagement can be encouraged by
      establishing universality around voice hearing early, reducing uncertainty,
      sharing difficulties with mindfulness practices, and mapping group progress to
      create a cohering sense of collaboration on therapy tasks.

PMID- 30095032
TI  - An Ounce of Prevention: Identifying Cues to (In)Action for Maternal Vaccine
      Refusal.
AB  - Recent increases in childhood vaccine exemption rates are a source of concern
      within the public health community. Drawing from the health belief model and in
      depth interviews with 50 mothers ( n = 50) who refused one or more vaccine, the
      aim of this study was to identify the specific reasons and the broader decision
      context(s) that underscored participants' vaccine refusal. Results indicate that
      the vast majority of participants supported vaccination until a particular cue
      motivated them to consider otherwise, and qualitative analysis identified three
      main categories into which these cues fell: perceived adverse reactions,
      endorsements from health care professionals, and perceived contradiction among
      expert-endorsed messages. These categories point to the central role of health
      communication in motivating vaccine refusal. Better understanding these cues can
      inform vaccine communication scholarship and practice, and also lend theoretical
      insight into the intertextual nature of controversial health messages and
      decisions.

PMID- 30095033
TI  - Hirudin variants production by genetic engineered microbial factory.
AB  - Hirudin was discovered as an active anticoagulant in leech extracts almost 60
      years ago. Since their initial discovery, hirudin and its variants have been
      produced with various anti-thrombotic, cancer cell inhibition, diabetic cataract
      treatment and anti-fatigue activities. Some hirudin variants have been approved
      for clinical use and released into the marketplace. Recent progress has seen made
      in relation to hirudin variants expressed in several well-established microbial
      hosts, including Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris and
      others, with high levels of activity and yield. This review summarizes the
      current progress on hirudin production using microbial producers, and considers
      the outlook for future development.

PMID- 30095034
TI  - Overweight and Obesity Differences Across Ethnically Diverse Subgroups of Asian
      American Men.
AB  - Asian Americans develop health complications at lower BMIs than other
      racial/ethnic groups. Given increasing overweight and obesity rates nationwide,
      growing numbers of Asian American men, and limited research on overweight and
      obesity in this population, understanding overweight and obesity differences
      across Asian subgroups of men is crucial to advancing health equity. This study
      examined overweight and obesity prevalence both among ethnic subgroups of Asian
      American men and compared to non-Hispanic White (NHW) men. Prevalence ratios were
      derived from 2002 to 2015 National Health Interview Survey data to determine
      associations between race/ethnicity and (a) overweight, and (b) obesity, across (
      n = 221,376) racial/ethnic groups of men (Chinese; Filipino; Asian Indian; Other
      Asian; NHW). Overweight and obesity for all Asian subgroups were defined using
      Asian-specific BMI cut points. Adjusted overweight prevalence was higher across
      all Asian subgroups compared to NHW men, except Filipinos. No significant
      pairwise relationships were observed for overweight prevalence among Asian
      subgroups. Filipinos had higher adjusted obesity prevalence compared to NHW men.
      Comparing among Asian American men, Asian Indians and Other Asians had higher
      adjusted obesity prevalence relative to Chinese. Filipinos had higher adjusted
      obesity prevalence compared to all other Asian subgroups (Chinese; Asian Indian;
      Other Asian). The current findings highlight the need for use of (a) WHO
      recommended Asian-specific BMI cut points and (b) data disaggregated by Asian
      American subgroup, to provide more accurate depictions of overweight and obesity
      rates and associated health risks. Accounting for subgroup differences is
      necessary to ensure Asian American men receive equitable, appropriate care.

PMID- 30095035
TI  - Effects of Reinstitution of Prolonged Mechanical Ventilation on the Outcomes of
      370 Patients in a Long-Term Acute Care Hospital.
AB  - OBJECTIVE: To investigate the effects of the reinstitution of continuous
      mechanical ventilator support of >21 days in 370 prolonged mechanical ventilation
      (PMV) patients, all free from ventilator support for >=5 days. METHODS: Four
      groups were formed based on the time and number of PMV reinstitutions and
      compared (group A: reinstitutions within 28 days, n = 51; group B: a single
      reinstitution after 28 days, n = 53; group C: multiple reinstitutions after 28
      days, n = 52; and group D: no known reinstitutions, n = 214). RESULTS: Of the 370
      patients, 156 (42%) required PMV reinstitutions. Most reinstitutions occurred
      within 7 months: 51 (33%) of the 156 patients within 28 days and 49 (31%) within
      the next 6 months. Group comparisons revealed a progression of outcomes from
      group A, the worst, to group D, the best, with groups B and C having intermediate
      but significantly different values. Decannulation was associated with an 88%
      decreased risk of PMV reinstitution and a 43% lower risk of death (all P < .001).
      CONCLUSION: Prolonged mechanical ventilation reinstitution rates were high, with
      most occurring within 7 months of freedom from MV. In general, the longer the
      period of ventilator freedom, the less the likelihood of a PMV reinstitution. The
      identification of 4 distinct PMV groups of patients by time and number of
      reinstitutions added useful prognostic information. Since PMV reinstitutions
      within 28 days lead to permanent MV support, >28 days of ventilator freedom
      provided an optimal cut point for assessing the likelihood of again requiring
      PMV.

PMID- 30095036
TI  - Understanding Interconnectedness From the Military Nurse Perspective.
AB  - BACKGROUND: Nurses who serve in the military have a unique perspective on nursing
      and health care delivery that nurtures wholeness and inspires peace and healing
      on a global scale. PURPOSE: The purpose of this study was to explore health
      promotion and healing from the military nurse perspective. DESIGN: Video-recorded
      interviews were conducted with 10 military nurses who represented various
      branches and times of service. Participants were asked to share their experiences
      as military nurses and discuss the challenges and rewards. FINDINGS: Thematic
      analysis of the recorded interviews revealed two major themes: interconnectedness
      and human potential. CONCLUSION: This study showed that military nurses have
      unique experiences that influenced their way of promoting health and healing.
      Interconnectedness with family (personal and military) had many positive and
      negative factors. Interconnectedness with the health care team was more prominent
      for the nurses during military service than in the civilian arena. Global
      interconnectedness included working with teams from around the world, helping
      children of detainees see that Americans were not evil, and caring for
      international communities. Military service strengthened the three human
      qualities of mind, body, and spirit, which resulted in increasing each military
      nurse's human potential by enabling them to serve as instruments of healing on a
      global scale.

PMID- 30095037
TI  - Kidney progression project (KiPP): Protocol for a longitudinal cohort study of
      progression in chronic kidney disease of unknown etiology in Sri Lanka.
AB  - Over the last two decades, a global epidemic of chronic kidney disease of unknown
      etiology (CKDu) has emerged in rural, arid, agricultural, lowland areas. Endemic
      regions have reported 15 to 20% prevalence among residents aged 30-60 years. CKDu
      is a progressive and irreversible disease resulting in renal failure and death in
      the absence of dialysis or a kidney transplant. While much of the research has
      focused on identifying etiology, this project seeks to ascertain factors
      associated with the rapidity of kidney disease progression in one of Sri Lanka's
      CKDu endemic areas. A sample of 296 male and female residents aged 21 to 65 with
      moderate CKD, as measured by their serum creatinine level, and a clinical
      diagnosis of CKDu are followed using quarterly serum testing to track the rate of
      progression. A baseline survey administered to the entire sample addresses
      potential risk factors, supplemented by a short survey focusing on changes
      through time. Concurrently water, soil and air are tested at the local and
      household levels. The study is the first to foster a multi-disciplinary approach
      that focuses on disease progression, identifying behavioural and exposure risk
      factors for rapid kidney function decline, in this progressively fatal disease.

PMID- 30095038
TI  - Biobanks and the Moral Concerns of Donors: A Democratic Deliberation.
AB  - Do members of the public believe that biobanks should accommodate the moral
      concerns of donors about the types of research done with their biospecimens? The
      answer to this question is critical to the future of genomic and precision
      medicine, endeavors that rely on a public willing to share their biospecimens and
      medical data. To explore public attitudes regarding the requirements of consent
      for biobank donations, we organized three democratic deliberations involving 180
      participants. The deliberative sessions involved small group discussions informed
      by presentations given by experts in both biobank research and ethics. We found
      that participants had a sophisticated understanding of the ethical problems of
      biobank consent and the complexity of balancing donor concerns while promoting
      research important to the future of health care. Our research shows how
      deliberative methods can offer policy makers creative ideas for accommodating the
      moral concerns of donors in the biobank consent process.

PMID- 30095039
TI  - Interactions Between Indigenous Women Awaiting Childbirth Away From Home and
      Their Southern, Non-Indigenous Health Care Providers.
AB  - We examine patient-provider interactions for Indigenous childbirth evacuees. Our
      analysis draws on in-depth interviews with 25 Inuit and First Nations women with
      medically high-risk pregnancies who were transferred or medevacked from northern
      Quebec to receive maternity care at a tertiary hospital in a southern city in the
      province. We supplemented the patient data with interviews from eight health care
      providers. Three themes related to patient-provider interactions are discussed:
      evacuation-related stress, hospital bureaucracy, and stereotypes. Findings show
      that the quality of the patient-provider interaction is contingent on individual
      health care providers' ability to connect with Indigenous patients and overcome
      cultural and institutional barriers to communication and trust-building. The
      findings point to the need for further training of medical professionals in the
      delivery of culturally safe care and addressing bureaucratic constraints in the
      health care system to improve patient-provider communication and overall
      relationship quality.

PMID- 30095040
TI  - Analysis of foot strike pattern, rearfoot dynamic and foot rotation over
      childhood. A cross-sectional study.
AB  - The purpose of this study was to determine the foot strike patterns (FSP),
      rearfoot position at initial contact (RPic, i.e., No INV/EVE) and foot rotation
      in children in relation to age. A total of 932 children aged 3 to 16 years
      participated in this study. A sagittal and frontal-plane video was recorded using
      a high-speed camcorder to analyse these variables. There is a significant
      increase (p < 0.001) of rearfoot strike patterns (RFS) prevalence in relation to
      age; e.g. preschool children (3-6 years old) displayed an RFS prevalence 46.65%
      and the adolescent population(15-16 years old) an RFS prevalence 92.20%. The
      total RFS prevalence in all samples was 69.25%. There was a significant reduction
      (p < 0.001) of prevalence of RPic in relation to age groups; preschool children
      displayed a prevalence of RPic 60.37% and the adolescent population 10%. There
      was a significant reduction (p < 0.001) of prevalence of no foot rotation in
      relation to age groups; preschool children displayed a prevalence of no foot
      rotation 48.95% and the adolescent population 13.55%. In conclusion, FSP in
      children are influenced by age. It is noteworthy that the RFS prevalence of
      children is lower in comparison to the adult population.

PMID- 30095041
TI  - Association of GSTT1/GSTM1 and ApoE variants with left ventricular diastolic
      dysfunction in thalassaemia major patients.
AB  - BACKGROUND: Cardiomyocytes are particularly susceptible to complications from
      iron loading. The blood transfusions in thalassaemia major create loading of iron
      that cannot be naturally excreted. Apolipoprotein E and Glutathione S-transferase
      act as the scavenger of free radicals, which are generated due to excess iron.
      The variants of Apolipoprotein E (ApoE) and Glutathione S-transferase (GST) may
      play a role in oxidative damage-induced cardiomyopathy, so we aimed to study the
      association of genetic variants of these genes on diastolic dysfunction in our
      patients. MATERIALS AND METHODS: One hundred and five beta-thalassaemia patients
      older than 10 years were enrolled for the study. Two-dimensional and M-mode
      echocardiography analysis was done in all patients. Genotyping of the genetic
      variants of aforementioned genes was done using the PCR-RFLP method. Serum
      Glutathione S-transferase levels were estimated by ELISA. RESULTS: Diastolic
      dysfunction was observed in 24 (22.8%) patients, whereas left ventricular
      hypertrophy was present in 37(35.2%) patients. There was a significant
      association of GSTM1 null allele with diastolic dysfunction only. Serum GST
      levels were also positively correlated with e/a and e/e' ratio. Positive
      association of ApoE E2 allele with the diastolic dysfunction was also seen.
      CONCLUSIONS: Patients having Glutathione S-transferase M1 allele and
      Apolipoprotein E E2 allele are predisposed to oxidative stress-induced cardiac
      injury.

PMID- 30095042
TI  - Veterans in Prison for Sexual Offenses: Characteristics and Reentry Service
      Needs.
AB  - Among prison-incarcerated men in the United States, more veterans (35%) have a
      sexual offense conviction than nonveterans (23%). Limited research has
      investigated factors explaining the link between military service and sexual
      offending. Nationally representative data from prison-incarcerated men ( n =
      14,080) were used to examine the association between veteran status and sexual
      offenses, adjusting for demographic, childhood, and clinical characteristics.
      Veterans had 1.35 higher odds (95% confidence interval = [1.12, 1.62], p < .01)
      of a sexual offense than nonveterans. Among veterans, those who were homeless or
      taking mental health medications at arrest had lower odds and veterans with a
      sexual trauma history had higher odds of a sexual offense compared with other
      offense types. Offering mental health services in correctional and health care
      settings to address trauma experiences and providing long-term housing options
      can help veterans with sexual offenses as they transition from prison to their
      communities.

PMID- 30095043
TI  - Atopic dermatitis: a look into systemic treatments and adherence considerations.

PMID- 30095044
TI  - Exploring the Use of Photo-Stories and Fiction Writing to Address HIV Stigma
      Among Health Professions Students.
AB  - HIV/AIDS stigma exists in healthcare and is harmful to people living with HIV
      (PLWH). Few anti-stigma interventions target undergraduate health professions
      students, although evidence supports reaching providers early in their training.
      We developed two different arts-based interventions based on Intergroup Contact
      Theory: a Photovoice intervention in which they viewed photo-stories of PLWH and
      a fiction writing intervention in which they developed characters with HIV. We
      present the results of a qualitative analysis of the post-intervention
      interviews, to elaborate on what and how students learned from both
      interventions. Via theme analysis, we identified three similar patterns among
      both sets of intervention participants. Interventions helped students to
      understand PLWH as "people first," experience emotional responses to PLWH, and
      complicated their understanding of who was living with HIV. All three themes
      illustrate how Photovoice and fiction writing interrupted stereotypes about PLWH
      and humanized PLWH to health professions students.

PMID- 30095046
TI  - Missed care: A need for careful ethical discussion.

PMID- 30095045
TI  - Costs of injuries and ill health in the workplace in South Korea.
AB  - Industrial accidents affect the sustainable development of any country,
      enterprise or individual. This study estimated the costs of loss due to
      industrial accidents in South Korea in 2013, based on the 4th Korean Working
      Conditions Survey. The total costs of loss were estimated at USD 27,224 million,
      with individuals losing the most at 79.5%, followed by employers at 20.4% and the
      government at 0.1%. These costs were equivalent to 2.1% of South Korea's gross
      domestic product in 2013. The costs to society/death due to industrial accidents
      were USD 640,000; USD 7000/individual out of work for <=3 days and USD
      242,000/individual out of work for >=4 days. These costs make it easy to
      calculate losses incurred due to industrial accidents. Costs of loss can also be
      used by the government as basic data to establish industrial safety and health
      policies.

PMID- 30095048
TI  - Numerical simulation of bypass evaporation system treating FGD wastewater using
      high temperature flue gas.
AB  - A novel zero-liquid discharge (ZLD) technology for desulfurization wastewater
      treatment is put forward in this paper. A ZLD reconstruction project performed on
      2 * 320 MW desulfurization system was taken as the research object, to study the
      evaporator structure and the key factors affecting spray evaporation through CFD
      numerical simulation. The result shows that when the evaporator diameter is 2.4
      m, the central density difference and the temperature difference of evaporator
      outlets are 0 kg/L and 0 degrees C, under this condition, the wall sticking can
      be avoided effectively, and the uniformity of evaporator's outlet flow field is
      improved. As for the same amount of wastewater, small atomized particle size,
      high flue gas flow rate and high flue gas temperature are conducive to complete
      evaporation, and the optimum atomized particle size is 100-150 MUm, flue gas
      velocity is 3-4 m/s and flue gas temperature is 250-260 degrees C. In order to
      reduce adverse impact on the main flue duct, the optimized design scheme that
      extracting flue gas before and after the air preheater is put forward in the
      purpose of energy saving.

PMID- 30095049
TI  - Understanding Healthy Protective Mechanisms Against Old Age.

PMID- 30095050
TI  - Looking Towards New Pathogenetic Mechanisms in Parkinson's Disease: is ANT1 the
      Potential Candidate?

PMID- 30095051
TI  - The Need of Time: Development of New Antimicrobials - Part II.

PMID- 30095052
TI  - Perturbation Theory Machine Learning Models: Theory, Regulatory Issues, and
      Applications to Organic Synthesis, Medicinal Chemistry, Protein Research, and
      Technology.
AB  - Machine Learning (ML) models are very useful to predict physicochemical
      properties of small organic molecules, proteins, proteomes, and complex systems.
      These methods may be useful to reduce the cost of research in terms of materials
      resources, time, and laboratory animal sacrifice. Recently different authors have
      reported Perturbation Theory (PT) methods combined with ML to obtain PTML (PT +
      ML) models. They have applied PTML models to the study of different biological
      systems and in technology as well. Here, we present one state-of- the-art review
      about the different applications of PTML models in Organic Synthesis, Medicinal
      Chemistry, Protein Research, and Technology. In this work, we also embrace an
      overview of regulatory issues for acceptance and validation of both: the
      Cheminformatics models, and the characterization of new Biomaterials. This is a
      main question in order to make scientific result self for humans and environment.

PMID- 30095053
TI  - Rational Surface Engineering of Colloidal Drug Delivery Systems for Biological
      Applications.
AB  - The use of colloidal particles as drug delivery carriers holds a great promise in
      terms of improvement of traditional treatment and diagnosis of human diseases.
      Nano- and microsized particles of a different composition including organic and
      inorganic materials can be fabricated with a great control over size, shape and
      surface properties. Nevertheless, only some few formulations have surpassed the
      benchtop and reached the bedside. The principal obstacle of colloidal drug
      delivery systems is their poor accumulation in target tissues, organs and cells,
      mainly by efficient sequestration and elimination by the mononuclear phagocytic
      system. Recent evidence suggests that, besides size, the surface character of
      colloidal systems is the most determinant design parameter that may ultimately
      guarantee successful biological performance. To approach these issues, materials
      designers and engineers can make use of multiple strategies and tools to finely
      modulate the particles' surface towards highly efficient and biocompatible
      materials. In this article, we provide an overview of the most relevant colloidal
      drug delivery systems, a summary of the available literature regarding the
      effects of surface charge, hydrophobicity and softness on biological response,
      and finally, we review the key points of surface modification strategies with
      organic, inorganic and biological materials.

PMID- 30095054
TI  - Targeted Drug Delivery Via Human Epidermal Growth Factor Receptor for Sustained
      Release of Allyl Isothiocyanate.
AB  - In this study, allyl-isothiocyanate (AITC)-loaded Polylactic-Co-Glycolic Acid
      (PLGA) Nanoparticles (NPs) were prepared for targeting epithelial squamous
      carcinoma cells using a specific antibody targeting the Epidermal Growth Factor
      (EGF) receptor overexpressed on the cell membranes. AITC-loaded PLGA NPs showed
      more effective anticancer properties compared with free AITC, and their
      cytotoxicity was even more pronounced when the anti-EGFR antibody was covalently
      attached to the NPs surface. This targeting ability was additionally tested by co
      culturing cervical HeLa cells, with very few EGFR on the membranes, and
      epithelial squamous carcinoma A431 cells, which largely overexpressed EFGR, being
      observed the specific localization of the antibody-functionalized AITC-loaded
      PLGA NPs solely in the latter types of cells, whereas non-functionalized NPs were
      distributed randomly in both cell types in much lesser extents. Thus, our
      findings support the development of drug delivery strategies that enhances the
      delivery of anti-cancer natural compounds to tumor tissue, in this case, by
      targeting specific tumor cell receptors with cell-specific ligands followed by
      tumor sensitization.

PMID- 30095055
TI  - Dermal Collagen Stabilization by Polyphenols and Spray Drying as an Encapsulation
      Strategy.
AB  - Collagen, the most abundant component in mammalian tissues, has a crucial impact
      at skin level. Both promotion and maintenance of cross-linked collagen at the
      skin are critical to sustain the functionality and appearance of that tissue.
      Lysyl oxidases, also known as LOX enzymes, are the major collagen cross-linking
      enzymes that play a pivotal role in homeostasis. This minireview summarizes
      evidence that describes an amino oxidase-like activity, which could be attributed
      to polyphenols, or where polyphenols could be required. We also discuss some
      available collagen formulations and the scientific evidence that describes the
      impact on dermal extracellular matrix. In addition, information about
      encapsulation strategies to carry polyphenols, and some examples are also
      provided.

PMID- 30095056
TI  - Mechanical Properties of Composite Hydrogels for Tissue Engineering.
AB  - Tissue engineering provides solutions that require medicine to restore damaged
      tissues or even complete organs. This discipline combines biologically active
      scaffolds, cells and molecules; being the addition of nanoparticles into the
      scaffolds, one of the techniques that is attracting more interest these days. In
      this work, Hydroxyapatite Nanorods (HA) were added to the network of Gelatin
      hydrogel (GE), and the particular properties resulting from their interaction
      were studied. Specifically, viscoelastic properties were characterized as a
      function of gel and nanoparticle concentration, varying ratios and temperatures.
      Oscillatory Time Sweeps (OTS) provided the necessary information about how the
      timeresolved material property/structure alteration. A wide variety of Continuous
      Flow Tests and Frequency Sweeps were used to describe the mechanical properties
      of the material, proving that the presence of nanoparticles led to a
      reinforcement of the gel network, mechanical stiffness and strength. The
      thixotropic nature of the gels was also evaluated and the most common theoretical
      models were described and commented. The attributes inferred from the data,
      showed a material that can allow the natural growth of bone tissue whilst
      withstanding properly the mechanical efforts; resulting in a material with an
      outstanding suitability to be used in regenerative medicine.

PMID- 30095057
TI  - Microencapsulation of Carvacrol Using Pectin/Aloe-gel as a Novel Wound Dressing
      Films.
AB  - Recently, Pectin (PEC) and Aloe-Gel (AG) have received great attention for their
      use in the encapsulation of hydrophobic bioactive compounds such as Carvacrol
      (CAR). The aim of this study is to assess the physical, chemical and biological
      properties of a novel PEC/AG film and evaluate its capability to entrap CAR into
      microencapsulates. For this purpose, the casting method was used to prepare the
      PEC/AG membranes (70:30 % w/w). The CAR-loaded PEC/AG film was prepared adding
      different proportions of CAR (0.25%, 0.50% and 1.00% v/v) to the mixture of
      PEC/AG, previously emulsified with tween 80 (1.0%). The optical properties, Water
      Vapor Permeability (WVP), ATR-FTIR spectroscopy, microstructure, antibacterial
      activity and size of microcapsules were evaluated. The PEC/AG membranes loaded
      with CAR showed yellowish appearance and they were transparent to the UV
      electromagnetic radiation (190, 200 and 280 nm). The film prepared with the
      lowest amount of CAR (PC/AG-CAR-0.25%) showed the highest values of WVP (66.2%)
      and, according to SEM micrograph, the largest microcapsules (~1005+/- 39 um3).
      The FTIR analysis showed the characteristic absorption peaks located at 1015 cm-1
      to 1030 cm-1 and a small shoulder to 990 cm-1 of benzene ring 1:2:4 substituted
      that suggested the presence of CAR-loaded in the PC/AG film. On the other hand,
      E. coli O157:H7 showed the highest sensitivity to the PEC/AG-CAR-1.00% film,
      while S. aureus was not sensitive.

PMID- 30095058
TI  - Cardiac Response to Exercise in Normal Ageing: What Can We Learn from Masters
      Athletes?
AB  - BACKGROUND: Ageing is associated with an inexorable decline in cardiac and
      vascular function, resulting in an increased risk of Cardiovascular Disease
      (CVD). Lifestyle factors such as exercise have emerged as a primary therapeutic
      target in the prevention of CVD, yet older individuals are frequently reported as
      being the least active, with few meeting the recommended physical activity
      guidelines. In contrast, well trained older individuals (Masters athletes) have
      superior functional capacity than their sedentary peers and are often comparable
      with young non-athletes. Therefore, the 'masters' athlete may be viewed as a
      unique non-pharmacological model which may allow researchers to disentangle the
      inexorable from the preventable and the magnitude of the unavoidable 'true'
      reduction in cardiac function due to ageing. CONCLUSION: This review examines
      evidence from studies which have compared cardiac structure and function in well
      trained older athletes, with age-matched controls but otherwise healthy.

PMID- 30095059
TI  - Human Umbilical Cord Mesenchymal Stem Cells Therapy for Insulin Resistance: A
      Novel Strategy in Clinical Implication.
AB  - There is increasing evidence reporting that as a common phenomenon in MetS
      relative diseases, insulin resistance (IR) is regarded as an independent
      etiological factor and a warning indicator of MetS occurrence. Therefore, for the
      special group (overweight or obesity), clinical regular monitoring of IR is an
      important basis for the prevention and early intervention of MetS relative
      diseases. This surveys reveals that human umbilical cord mesenchymal stem cells
      (HUC-MSCs)possess a kind of potential: it may become a possible theraphy for IR
      in type 2 diabetes mellitus (T2DM) and related diseases. Specific emphasis is
      focused on evaluating the improvement IR function of HUC-MSCs under the
      background of development in vitro and in vivo. Next, the action mechanisms of
      HUC-MSCs is discussed, and some of their advantages and disadvantages in the
      course of clinic application are presented. The final section highlights the
      application of HUC-MSCs in T2DM and relative diseases at this stage. Up to now,
      although many questions remain unresolved, we still consider that HUC-MSCs is one
      of the best therapy ameliorating IR in the future.

PMID- 30095060
TI  - Breast Cancer Stem Cells and Sex Steroid Hormones.
AB  - Breast cancer stem cells (BCSCs) are a small population of tumor-initiating cells
      that express stem cell-associated markers. In recent years, their properties and
      mechanisms of regulation have become a focus for intense research due to their
      intrinsic resistance to conventional cancer therapies. This review describes
      breast cancer stem cell origin, signaling pathways involved in self-renewal, such
      as Wnt, Notch and Hedgehog, biomarkers linked to stemness, and the role of sex
      steroid hormones on BCSC regulation.

PMID- 30095061
TI  - ALDH as a Stem Cell marker in solid tumors.
AB  - Aldehyde dehydrogenase [ALDH] is an enzyme that participates in important
      cellular mechanisms as aldehyde detoxification and retinoic acid synthesis;
      moreover, ALDH activity is involved in drug resistance, a characteristic of
      cancer stem cells [CSCs]. Even though ALDH is found in stem cells, CSCs and
      progenitor cells, this enzyme has been successfully used to identify and isolate
      cell populations with CSC properties from several tumor origins. ALDH is
      allegedly involved in cell differentiation through its product, retinoic acid.
      However, direct or indirect ALDH inhibition, using specific inhibitors or
      retinoic acid, has shown a reduction in ALDH, along with loss of stem cell
      traits, reduction of cell proliferation, invasion, and drug sensitization. For
      these reasons, ALDH and retinoic acid are promising therapeutic targets. This
      review summarizes the current evidence for ALDH as a CSCs marker in solid tumors,
      as well as current knowledge about the functional roles of ALDH in CSCs. We
      discuss the controversy of ALDH activity to maintain CSC stemness, or conversely,
      to promote cell differentiation. Finally, we review the advances in using ALDH
      inhibitors as an anti-cancer drugs.

PMID- 30095062
TI  - Adolescents' diet quality in relation to their relatives' and peers' diet
      engagement and encouragement: the Healthy Lifestyle in Europe by Nutrition in
      Adolescence (HELENA) study.
AB  - OBJECTIVE: To examine the associations between adolescents' diet quality and
      their perceived relatives' and peers' diet engagement and encouragement. DESIGN:
      Cross-sectional study performed in European countries. Diet quality was scored
      using the Diet Quality Index for Adolescents (DQI-A) based on four components:
      quality, diversity, balance and meal frequency. Perceived diet quality engagement
      and perceived encouragement of the relatives/peers were assessed using the
      questions 'How healthy is each of the following persons' diet?' and 'How often
      does each of the following persons encourage you to eat a healthy diet?' SETTING:
      Vienna, Ghent, Lille, Athens, Heraklion, Pecs, Rome, Dortmund, Zaragoza and
      Stockholm. SUBJECTS: Healthy adolescents (n 2943). RESULTS: The perceived
      engagement level of the mother, father and sister was each positively associated
      with the DQI-A (P<0.05). A positive association was found for the perceived
      engagement level of siblings, father and mother with all specific components
      (P<0.05). DQI-A was negatively associated with the perceived encouragement level
      from a best friend and positively associated with the encouragement level of the
      mother and father (P<0.05). Diversity, balance and quality components were
      positively associated with the perceived encouragement level from the mother and
      father (P<0.05), whereas the best friend's perceived encouragement was negatively
      associated with the meal frequency component (P<0.01). CONCLUSIONS: These
      findings highlight the role of social engagement and encouragement of relatives
      and peers in adolescents' diet quality. Intervention or promotion programmes
      aimed at enhancing diet quality in adolescents should target both family and
      peers.

PMID- 30095063
TI  - Protein and bone health across the lifespan.
AB  - Bone health is determined by the rate of accrual in early life, followed by the
      rate of age-associated bone loss. Dietary protein intake might have a role in
      bone health across both of these phases via pleiotropic mechanistic pathways.
      Herein we summarise the pathways through which protein may exert either a
      positive or negative influence on bone. In the introduction, we describe the acid
      ash hypothesis, which states that a high-protein intake may lead to an acidic
      residue that must be neutralised through the leaching of calcium and other
      minerals from the bone, subsequently leading to demineralisation and bone
      weakening. Conversely, and as described in the 'Against: mechanisms through which
      protein may negatively impact bone' section, protein intake may act to strengthen
      the bone by stimulating the activity of various anabolic hormones and growth
      factors, or by optimising muscle mass and functionality, which itself has an
      osteogenic influence. The net effect of these contrasting pathways is described
      in the 'For: mechanisms through which protein may positively impact bone'
      section, where a number of meta-analyses have demonstrated that higher protein
      intakes have a small positive impact on bone mass and fracture risk. Sometimes
      higher than recommended protein intakes are advised, e.g. during the earlier and
      later phases of the lifespan or during reduced energy availability. We conclude
      that protein is an essential nutrient for bone health, although further research
      is required to clarify the mechanistic pathways through which it exerts its
      influence, along with the clarification of the quantities, food sources and
      timing to allow for the optimisation of this protective influence and ultimately
      a reduction in fracture risk.

PMID- 30095064
TI  - Positive maternal mental health during pregnancy associated with specific forms
      of adaptive development in early childhood: Evidence from a longitudinal study
      CORRIGENDUM.

PMID- 30095065
TI  - Self-reported adherence to foot care in type 2 diabetes patients: do illness
      representations and distress matter?
AB  - : AimThis study examined the differences and the predictive role of clinical
      variables, illness representations, anxiety, and depression symptoms, on self
      reported foot care adherence, in patients recently diagnosed with type 2 diabetes
      mellitus (T2DM) and assessed no longer than a year after the diagnosis (T1) and
      four months later (T2). BACKGROUND: The high rate of diabetes worldwide is one of
      the major public health challenges. Foot care is the behavior least performed by
      patients although regular foot care could prevent complications such as diabetic
      foot and amputation. Psychosocial processes such as illness representations and
      distress symptoms may contribute to explain adherence to foot self-care
      behaviors. METHODS: This is a longitudinal study with two assessment moments. The
      sample included 271 patients, who answered the Revised Summary of Diabetes Self
      Care Activities, Brief-Illness Perception Questionnaire, and Hospital Anxiety and
      Depression Scale.FindingsPatients reported better foot care adherence at T2.
      Having a higher duration of T2DM and the perception of more consequences of
      diabetes were associated with better self-reported foot care adherence, at T1. At
      T2, the predictors were lower levels of HbA1c, better self-reported foot care
      adherence at T1, higher comprehension about T2DM, as well as fewer depressive
      symptoms. Interventions to promote adherence to foot care should have in
      consideration these variables. The results of the present study may help health
      professionals in designing interventions that early detect depressive symptoms
      and address illness beliefs, in order to promote foot self-care behaviors
      reducing the incidence of future complications.

PMID- 30095066
TI  - Efficient analysis of mammalian polysomes in cells and tissues using Ribo Mega
      SEC.
AB  - We describe Ribo Mega-SEC, a powerful approach for the separation and biochemical
      analysis of mammalian polysomes and ribosomal subunits using Size Exclusion
      Chromatography and uHPLC. Using extracts from either cells, or tissues, polysomes
      can be separated within 15 min from sample injection to fraction collection. Ribo
      Mega-SEC shows translating ribosomes exist predominantly in polysome complexes in
      human cell lines and mouse liver tissue. Changes in polysomes are easily
      quantified between treatments, such as the cellular response to amino acid
      starvation. Ribo Mega-SEC is shown to provide an efficient, convenient and highly
      reproducible method for studying functional translation complexes. We show that
      Ribo Mega-SEC is readily combined with high-throughput MS-based proteomics to
      characterize proteins associated with polysomes and ribosomal subunits. It also
      facilitates isolation of complexes for electron microscopy and structural
      studies.

PMID- 30095067
TI  - Structure of the human volume regulated anion channel.
AB  - SWELL1 (LRRC8A) is the only essential subunit of the Volume Regulated Anion
      Channel (VRAC), which regulates cellular volume homeostasis and is activated by
      hypotonic solutions. SWELL1, together with four other LRRC8 family members,
      potentially forms a vastly heterogeneous cohort of VRAC channels with different
      properties; however, SWELL1 alone is also functional. Here, we report a high
      resolution cryo-electron microscopy structure of full-length human homo-hexameric
      SWELL1. The structure reveals a trimer of dimers assembly with symmetry mismatch
      between the pore-forming domain and the cytosolic leucine-rich repeat (LRR)
      domains. Importantly, mutational analysis demonstrates that a charged residue at
      the narrowest constriction of the homomeric channel is an important pore
      determinant of heteromeric VRAC. Additionally, a mutation in the flexible N
      terminal portion of SWELL1 affects pore properties, suggesting a putative link
      between intracellular structures and channel regulation. This structure provides
      a scaffold for further dissecting the heterogeneity and mechanism of activation
      of VRAC.

PMID- 30095070
TI  - Correction to Lancet Planet Health 2017; 1: e188-99.

PMID- 30095071
TI  - Correction to Lancet Planet Health 2017; 2: e64-73.

PMID- 30095068
TI  - Release and spread of Wingless is required to pattern the proximo-distal axis of
      Drosophila renal tubules.
AB  - Wingless/Wnts are signalling molecules, traditionally considered to pattern
      tissues as long-range morphogens. However, more recently the spread of Wingless
      was shown to be dispensable in diverse developmental contexts in Drosophila and
      vertebrates. Here we demonstrate that release and spread of Wingless is required
      to pattern the proximo-distal (P-D) axis of Drosophila Malpighian tubules.
      Wingless signalling, emanating from the midgut, directly activates odd skipped
      expression several cells distant in the proximal tubule. Replacing Wingless with
      a membrane-tethered version that is unable to diffuse from the Wingless producing
      cells results in aberrant patterning of the Malpighian tubule P-D axis and
      development of short, deformed ureters. This work directly demonstrates a
      patterning role for a released Wingless signal. As well as extending our
      understanding about the functional modes by which Wnts shape animal development,
      we anticipate this mechanism to be relevant to patterning epithelial tubes in
      other organs, such as the vertebrate kidney.

PMID- 30095072
TI  - Correction to Lancet Planet Health 2017; 1: e15-16.

PMID- 30095073
TI  - Dermatological emergencies in tropical zones: 189 dermatology cases in Dakar.
AB  - to assess : the frequency of emergencies among patients admitted to dermatology
      departments in Dakar, their most common causes, mortality rate, and the most
      frequent dermatoses. This one-year prospective study took place in the two
      reference departments for the treatment of dermatological diseases in Dakar. We
      have included all patients with a dermatological emergency, regardless of age and
      gender, as determined by the doctor receiving the patient. The data were entered
      in Excel and analyzed with R software, version 3.1.2. the study included 189
      patients, 40 % of all dermatology department admissions. The sex ratio was 0.89
      (M/F) and the average age 49 years. The mean time from arrival to treatment was
      30 minutes. Absolute emergencies accounted for 45.4 % of these emergencies, and
      relative emergencies 54.6 %. Absolute emergencies were dominated by severe drug
      eruptions (17 %) and relative emergencies by infectious dermatoses (38 %).
      Emergency measures were carried out in all cases, associated with etiological
      treatment. The mortality rate was 7 % (n=14), and 5 (36 %) of these deaths were
      due to severe drug eruptions. Infectious dermatoses and severe drug eruptions are
      the most frequent emergencies. The high mortality rate, related mostly to drug
      eruptions, indicates the need for early management and an adequate technical
      platform.

PMID- 30095069
TI  - A transient cortical state with sleep-like sensory responses precedes emergence
      from general anesthesia in humans.
AB  - During awake consciousness, the brain intrinsically maintains a dynamical state
      in which it can coordinate complex responses to sensory input. How the brain
      reaches this state spontaneously is not known. General anesthesia provides a
      unique opportunity to examine how the human brain recovers its functional
      capabilities after profound unconsciousness. We used intracranial
      electrocorticography and scalp EEG in humans to track neural dynamics during
      emergence from propofol general anesthesia. We identify a distinct transient
      brain state that occurs immediately prior to recovery of behavioral
      responsiveness. This state is characterized by large, spatially distributed, slow
      sensory-evoked potentials that resemble the K-complexes that are hallmarks of
      stage two sleep. However, the ongoing spontaneous dynamics in this transitional
      state differ from sleep. These results identify an asymmetry in the
      neurophysiology of induction and emergence, as the emerging brain can enter a
      state with a sleep-like sensory blockade before regaining responsivity to
      arousing stimuli.

PMID- 30095074
TI  - Chronic leg ulcers in hospitalized patients in Lome, Togo: 125 cases.
AB  - The aim of this study was to document the profile and causes of chronic leg
      ulcers (CLU) in patients hospitalized in Lome, Togo. This retrospective study
      reviewed records from the dermatology departments (CHU Sylvanus Olympio and
      Campus, and the dermatology center of Gbossime) from 2000 to 2017 and from the
      general surgery department of CHU Sylvanus Olympio from 2013 to 2017 to identify
      cases. In all, 125 cases of CLU were identified during the study period. The
      patients' mean age was 56.6 years and the sex ratio (M/F) was 0.89. The average
      time from CLU onset to consultation was 10.9 weeks (range : 7 weeks to 4 years).
      They were mainly associated with a history of diabetes (32 cases), arterial
      hypertension (16 cases), varicose veins (14 cases), and malnutrition (14 cases).
      The main causes were : ulcers of infectious origin in 49.6% of cases (including
      38 with phagedenic ulcers), ulcers of vascular origin in 36% (including 21 cases
      with a venous ulcer) and diabetic ulcers in 8.8% of cases. The ulcer was
      unilateral in 122 patients (67 on the right and 55 on the left) and bilateral in
      3 patients. The locations were the foot in 56 cases, the leg in 37 cases, and leg
      and foot in 32 cases. In addition to dressings, surgical debridement was
      performed in 23 patients, followed by skin autografts for 16. Amputation was
      performed for 31 patients. Sixteen (12.8%) of the 125 patients died. Our study
      observed a high rate of phagedenic ulcers among CLU in Togo. It also pointed to a
      problem explaining the very high mortality rate: delayed consultation by patients
      who arrive only after the onset of complications.

PMID- 30095075
TI  - Probable dysimmune epilepsia partialis continua manifesting as epileptic moving
      toes syndrome: electroclinical features of a challenging case.
AB  - Epilepsia partialis continua (EPC) is a rare form of focal status epilepticus. We
      describe a 22-year-old woman with EPC manifesting with isolated toe movements,
      prevalent over the left side and initially misdiagnosed as psychogenic,
      clinically almost indistinguishable from those observed in "painful legs and
      moving toes syndrome". The continuous involuntary movements with EMG correlates
      of twitches lasting <100 ms, the sharp waves over fronto-central regions on EEG,
      and the marked asymmetry in somatosensory evoked potentials with higher cortical
      amplitude over the right side following peripheral stimulation over the left foot
      confirmed the epileptic nature of the symptoms, leading to the diagnosis of EPC.
      The toe movements were markedly reduced following steroid therapy, whereas the
      infusion of immunoglobulins caused aseptic meningitis. Despite an extensive
      diagnostic work-up (including a search for antibodies for paraneoplastic and
      autoimmune encephalitis), an ultimate aetiological diagnosis was not reached,
      although the dramatic response to corticosteroids strongly supported an
      underlying dysimmune pathophysiology. Diagnosing EPC can be challenging,
      especially if movements are confined to a very small body region or strongly
      resemble movements encountered in other conditions. EEG-EMG monitoring should be
      performed in patients with continuous involuntary muscular jerks in order not to
      overlook a diagnosis of EPC. [Published with video sequences on
      www.epilepticdisorders.com].

PMID- 30095076
TI  - Tetanus after application of traditional topical treatment to a severe burn.
AB  - A 2-year-old child was accompanied by his parents to the pediatric emergency room
      for refusal to eat, trismus and generalized contractures four days after the
      application of a traditional topical treatment (Cassava leaves) on lesions of a
      severe thermal burn. A temperature of 38C, a heart rate of 114 beats/min, and a
      blood pressure of 90/60 mm Hg were recorded. The tetanus vaccination was not up
      to date. The diagnosis of tetanus was immediately suggested. Antitetanus serum
      (immunoglobulin), an antibiotic (amoxicillin and clavulanic acid), and a
      myorelaxant (benzodiazepine) were administered. Local treatments were also
      performed. The child died within 24 hours.

PMID- 30095077
TI  - RapidBrachyMCTPS: a Monte Carlo-based treatment planning system for brachytherapy
      applications.
AB  - Despite being considered the gold standard for brachytherapy dosimetry, Monte
      Carlo (MC) has yet to be implemented into a software for brachytherapy treatment
      planning. The purpose of this work is to present RapidBrachyMCTPS, a novel
      treatment planning system (TPS) for brachytherapy applications equipped with a
      graphical user interface (GUI), optimization tools and a Geant4-based MC dose
      calculation engine, RapidBrachyMC. Brachytherapy sources and applicators were
      implemented in RapidBrachyMC and made available to the user via a source and
      applicator library in the GUI. To benchmark RapidBrachyMC, TG-43 parameters were
      calculated for the microSelectron v2 (192Ir) and SelectSeed (125I) source models
      and were compared against previously validated MC brachytherapy codes. The
      performance of RapidBrachyMC was evaluated for a prostate high dose rate case. To
      assess the accuracy of RapidBrachyMC in a heterogeneous setup, dose distributions
      with a cylindrical shielded/unshielded applicator were validated against film
      measurements in a Solid WaterTM phantom. TG-43 parameters calculated using
      RapidBrachyMC generally agreed within 1%-2% of the results obtained in previously
      published work. For the prostate case, clinical dosimetric indices showed general
      agreement with Oncentra TPS within 1%. Simulation times were on the order of
      minutes on a single core to achieve uncertainties below 2% in voxels within the
      prostate. The calculation time was decreased further using the multithreading
      features of Geant4. In the comparison between MC-calculated and film-measured
      dose distributions, at least 95% of points passed the 3%/3 mm gamma index
      criteria in all but one case. RapidBrachyMCTPS can be used as a post-implant
      dosimetry toolkit, as well as for MC-based brachytherapy treatment planning. This
      software is especially well suited for the development of new source and
      applicator models.

PMID- 30095078
TI  - Modeling experimental recordings of vagal afferent signaling of intestinal
      inflammation for neuromodulation.
AB  - OBJECTIVE: Artificial modulation of peripheral nerve signals (neuromodulation) by
      electrical stimulation is an innovation with potential to develop treatments that
      replace or supplement drugs. One function of the nervous system that can be
      exploited by neuromodulation is regulation of disease intensity. Optimal
      interfacing of devices with the nervous system requires suitable models of
      peripheral nerve systems so that closed-loop control can be utilized for
      therapeutic benefit. APPROACH: We use physiological data to model afferent
      signaling in the vagus nerve that carries information about inflammation in the
      small intestine to the brain. MAIN RESULTS: The vagal nerve signaling system is
      distributed and complex; however, we propose a class of reductive models using a
      state-space formalism that can be tuned in a patient-specific manner.
      SIGNIFICANCE: These models provide excellent fits to a large range of nerve
      recording data but are computationally simple enough for feedback control in
      implantable neuromodulation devices.

PMID- 30095079
TI  - Comparing brain connectivity metrics: a didactic tutorial with a toy model and
      experimental data.
AB  - OBJECTIVE: The objective of this paper is to didactically compare resting state
      connectivity networks computed using two different methods called phase locking
      value (PLV) and convergent cross-mapping (CCM). PLV is a ubiquitous measure of
      connectivity in electrophysiological research but is less often applied to fMRI
      BOLD timeseries since this model-based metric assumes that oscillatory coupling
      is a sufficient condition for connectivity. Alternatively, CCM is a model-free
      method, which detects potentially nonlinear causal influences based on the
      ability to estimate one timeseries with another and does not assume an
      oscillatory structure. APPROACH: We use a toy dataset to test the PLV and CCM
      algorithms under different known synchronization conditions. Additionally,
      experimental resting state EEG and fMRI datasets are used for comparison. MAIN
      RESULTS: The results show that the resting state brain networks computed using
      both algorithms produce similar results for both resting state EEG and fMRI
      datasets. For both neuroimaging datasets, the network characteristics follow the
      same trends and the similarity between the computed networks, for both
      algorithms, is highly significant. SIGNIFICANCE: CCM is able to identify low or
      one-way connection strengths better than PLV but takes exponentially longer to
      compute. Based on these results, PLV provides a good metric for on-line network
      identification because it is both computationally fast and an excellent
      approximation of the network computed with CCM.

PMID- 30095080
TI  - Performance of radon monitors in a purpose-built radon chamber.
AB  - The purpose of this paper is to benchmark several different radon monitors, by
      quantifying their accuracy and response time. Radon monitors with different
      characteristics were tested in a purpose-built radon chamber under reference
      conditions. The radon concentration in the chamber was controlled and maintained
      at a stable radon concentration of (2648 +/- 85) Bq m-3 to evaluate the accuracy
      and precision of these monitors. The response time of the monitors was analysed
      for two time intervals. To assess the response time of the monitors, radon
      concentration was varied from a theoretical value of 0-6441 Bq m-3 and then from
      6441 to 2648 Bq m-3. The results from this study show that general purpose radon
      monitors are less accurate than those used by radon testing service providers and
      the research community. All monitors tested reported a mean radon concentration
      within the +/-10% of the reference detector value at the radon equilibrium
      concentration. Different response time analysis methods were proposed and
      discussed, and for the particular time intervals analysed, response time was
      found to be slower for those radon monitors intended for general purpose
      applications.

PMID- 30095081
TI  - Two-stage three-channel Kondo physics for an FePc molecule on the Au(1 1 1)
      surface.
AB  - We study an impurity Anderson model to describe an iron phthalocyanine (FePc)
      molecule on Au(1 1 1), motivated by previous results of scanning tunneling
      spectroscopy (STS) and theoretical studies. The model hybridizes a spin doublet
      consisting in one hole at the [Formula: see text] orbital of iron and two
      degenerate doublets corresponding to one hole either in the 3d xz or in the 3d yz
      orbital (called pi orbitals) with two degenerate Hund-rule triplets with one hole
      in the 3d z orbital and another one in a pi orbital. We solve the model using a
      slave-boson mean-field approximation (SBMFA). For reasonable parameters we can
      describe very well the observed STS spectrum between sample bias  -60 mV to 20
      mV. For these parameters the Kondo effect takes place in two stages, with
      different energy scales [Formula: see text] corresponding to the Kondo
      temperatures related with the hopping of the z 2 and pi orbitals respectively.
      There is a strong interference between the different channels and the Kondo
      temperatures, particularly the lowest one is strongly reduced compared with the
      value in the absence of the competing channel.

PMID- 30095082
TI  - Effect of nanostructures on anchoring stem cell-derived neural tissue to
      artificial surfaces.
AB  - OBJECTIVE: Chronic application of brain implants monitoring or modulating
      neuronal activity are hindered by the foreign body response of the tissue.
      Topographical modification of implant surfaces may reduce negative tissue
      response by imitating the structure of the extracellular matrix and therefore
      affecting the attachment and behavior of neural cells. APPROACH: In our in vitro
      study, the effect of nanostructuring was investigated on two commercially used
      neural implant materials: silicon and platinum. The adhesion, survival and
      arrangement of neural stem cells (NE4C) and microglial cells (BV2) were
      investigated and compared to nanostructured and flat Si and Pt surfaces using
      cell viability studies and fluorescent microscopy image analysis. MAIN RESULTS:
      Our data indicated that neural cells established strong adhesive couplings with
      each other, instead of binding to the artificial surfaces. SIGNIFICANCE: The
      phenomena resemble some features of in vivo separation of living tissue from the
      implanted artificial material, providing an in vitro model for studying immune
      response.

PMID- 30095083
TI  - Improved discrimination between benign and malignant LDCT screening-detected lung
      nodules with dynamic over static 18F-FDG PET as a function of injected dose.
AB  - Lung cancer mortality rate can be significantly reduced by up to 20% through
      routine low-dose computed tomography (LDCT) screening, which, however, has high
      sensitivity but low specificity, resulting in a high rate of false-positive
      nodules. Combining PET with CT may provide more accurate diagnosis for
      indeterminate screening-detected nodules. In this work, we investigated low-dose
      dynamic 18F-FDG PET in discrimination between benign and malignant nodules using
      a virtual clinical trial based on patient study with ground truth. Six patients
      with initial LDCT screening-detected lung nodules received 90 min single-bed PET
      scans following a 10 mCi FDG injection. Low-dose static and dynamic images were
      generated from under-sampled list-mode data at various count levels (100%, 50%,
      10%, 5%, and 1%). A virtual clinical trial was performed by adding nodule
      population variability, measurement noise, and static PET acquisition start time
      variability to the time activity curves (TACs) of the patient data. We used
      receiver operating characteristic (ROC) analysis to estimate the classification
      capability of standardized uptake value (SUV) and net uptake constant K i from
      their simulated benign and malignant distributions. Various scan durations and
      start times (t *) were investigated in dynamic Patlak analysis to optimize
      simplified acquisition protocols with a population-based input function (PBIF).
      The area under curve (AUC) of ROC analysis was higher with increased scan
      duration and earlier t *. Highly similar results were obtained using PBIF to
      those using image-derived input function (IDIF). The AUC value for K i using
      optimized t * and scan duration with 10% dose was higher than that for SUV with
      100% dose. Our results suggest that dynamic PET with as little as 1 mCi FDG could
      provide discrimination between benign and malignant lung nodules with higher than
      90% sensitivity and specificity for patients similar to the pilot and simulated
      population in this study, with LDCT screening-detected indeterminate lung
      nodules.

PMID- 30095084
TI  - Clinical deep brain stimulation strategies for orientation-selective pathway
      activation.
AB  - OBJECTIVE: This study investigated stimulation strategies to increase the
      selectivity of activating axonal pathways within the brain based on their
      orientations relative to clinical deep brain stimulation (DBS) lead implants.
      APPROACH: Previous work has shown how varying electrode shape and controlling the
      primary electric field direction through preclinical electrode arrays can produce
      orientation-selective axonal stimulation. Here, we significantly extend those
      results using computational models to evaluate the degree to which clinical DBS
      leads can direct stimulus-induced electric fields and generate orientation
      selective activation of fiber pathways in the brain. Orientation-selective pulse
      paradigms were evaluated in conceptual models and in patient-specific models of
      subthalamic nucleus (STN)-DBS for treating Parkinson's disease. MAIN RESULTS:
      Single-contact monopolar or two-contact bipolar stimulation through clinical DBS
      leads with cylindrical electrodes primarily activated axons orientated parallel
      to the lead. Conversely, multi-contact monopolar stimulation with a cathode
      leading pulse waveform selectively activated axons perpendicular to the DBS lead.
      Clinical DBS leads with segmented rows of electrodes and a single current source
      provided additional angular resolution for activating axons oriented 0 degrees ,
      +/-22.5 degrees , +/-45 degrees , +/-67.5 degrees , or 90 degrees  relative to
      the lead shaft. Employing multiple independent current sources to deliver unequal
      amounts of current through these leads further increased the angular resolution
      of activation relative to the lead shaft. The patient-specific models indicated
      that multi-contact cathode configurations, which are rarely used in clinical
      practice, could increase activation of the hyperdirect pathway collaterals
      projecting into STN (a putative therapeutic target), while minimizing direct
      activation of the corticospinal tract of internal capsule, which can elicit
      sensorimotor side-effects when stimulated. SIGNIFICANCE: When combined with
      patient-specific tissue anisotropy and patient-specific anatomical morphologies
      of neural pathways responsible for therapy and side effects, orientation
      selective DBS approaches show potential to significantly improve clinical
      outcomes of DBS therapy for a range of existing and investigational clinical
      indications.

PMID- 30095085
TI  - Benchtop magnetic particle relaxometer for detection, characterization and
      analysis of magnetic nanoparticles.
AB  - This paper presents the design, construction, and testing of a magnetic particle
      relaxometer (MPR) to assess magnetic nanoparticle response to dynamic magnetic
      fields while subjected to a bias field. The designed MPR can characterize
      magnetic particles for use as tracers in magnetic particle imaging (MPI), with
      the variation of an applied bias field emulating the scan of the MPI field free
      point. The system applies a high-frequency time-varying excitation field (up to
      45 mT at 30 kHz), while slowly ramping a bias field (+/-100 mT in 1 s). The time
      resolved response of the sample is measured using an inductive sensing coil
      system, made of a pick-up coil and a rotating and translating balancing coil to
      finely cancel the induction feed-through from the excitation field. A post
      processing algorithm is presented to extract the tracer response related to the
      point spread function for MPI applications, and the performance of the MPR is
      demonstrated using superparamagnetic iron oxide particles (ferucarbotran).

PMID- 30095087
TI  - Hyaluronic acid dermal fillers in the management of recurrent angular cheilitis:
      a case report.
AB  - An immediate, successful result - pain and symptom free one year later.

PMID- 30095086
TI  - Comparison of Contrast-Enhanced Ultrasound and Positron Emission
      Tomography/Computed Tomography (PET/CT) in Lymphoma.
AB  - BACKGROUND This study aimed to assess the value of contrast-enhanced ultrasound
      (CEUS) in the diagnosis and prognosis of lymphoma based on PET-CT. MATERIAL AND
      METHODS Our study included 88 superficial lymph nodes and 63 patients who
      underwent ultrasound-guided biopsy or surgery for pathology from October 2015 to
      March 2017. All lymph nodes were assessed by CEUS and PET-CT. CEUS and PET-CT
      parameters were recorded, including arrive time (AT), time to peak (TTP), base
      intensity (BI), peak intensity (PI), ascending slope (AS), descending slope (DS),
      area under the TIC curve (AUC), maximum standardized uptake value (SUVmax), and
      mean standardized uptake value (SUVmean). Pearson's correlation was used to
      assess the associations of CEUS and PET-CT parameters. RESULTS Of the 88 lymph
      nodes examined,12 were Hodgkin's lymphoma (HL) and76 were non-Hodgkin's lymphoma
      (NHL). The variations of CEUS dose parameters (DeltaI, AUC, and AS) were
      positively correlated with PET-CT results (SUVmax and TLG). Correlation
      coefficients were 0.609, 0.518, 0.456, 0.630, 0.593, and 0. 532, respectively.
      The remaining time values (AT, TP, and DeltaT) were negatively associated with
      PET-CT results. Correlation coefficients were -0.239, -0.272, -0.284and -0.377, 
      0.391, and -0.320, respectively. CONCLUSIONS Quantitative CEUS data were
      correlated with PET-CT values, with potential use in the diagnosis of lymphoma.

PMID- 30095088
TI  - Standards of conduct.

PMID- 30095089
TI  - Refugee healthcare: Refugees in crisis.

PMID- 30095090
TI  - Tooth whitening: A grey area.

PMID- 30095091
TI  - University spinout secures L2 million contract to export toothpaste tech to
      China.

PMID- 30095092
TI  - Treatment modalities for burning mouth syndrome : a systematic review.
AB  - Multi-disciplinary treatment modalities may be needed.

PMID- 30095093
TI  - HPV Report: Government green-lights HPV virus for boys.

PMID- 30095095
TI  - Amalgam alternatives: replacing the irreplaceable?

PMID- 30095094
TI  - Current registration fees comparison between regulators.

PMID- 30095096
TI  - Oral surgery: Labial frenectomy: Indications and practical implications.

PMID- 30095097
TI  - System to encourage child tooth hygiene.

PMID- 30095098
TI  - New partnership will help children with cleft lip.

PMID- 30095100
TI  - School children to be trained in healthy eating.

PMID- 30095099
TI  - Low sugar version of leading milk chocolate bar coming in 2019.

PMID- 30095102
TI  - Dentists to receive 2% pay rise from October.

PMID- 30095101
TI  - Composite of choice.

PMID- 30095103
TI  - Sense of humour?

PMID- 30095105
TI  - The use of tools to support oral lesion description in oral medicine referrals.
AB  - The use of response prompts improves the quality of referral letters.

PMID- 30095104
TI  - Midlands boost for dental access.

PMID- 30095106
TI  - Diagnostic pathway of oral cavity cancer in an integrated health care system.
AB  - Dentists have an important role to play in screening.

PMID- 30095108
TI  - International lab experts form Global Lab Experts Network.

PMID- 30095107
TI  - Learn how to wow patients at OHC 2018.

PMID- 30095109
TI  - New injectable restorative claims to be strong as a rock.

PMID- 30095111
TI  - Specialist knowledge at your fingertips.

PMID- 30095110
TI  - HIV: Support the patients, not the stigma.

PMID- 30095112
TI  - Dental market debated at DentalForum event.

PMID- 30095113
TI  - Expert tips on periodontal diagnosis.

PMID- 30095114
TI  - Scottish oral drive needs detailed and funded plans.

PMID- 30095117
TI  - The 'cereal' killer on your breakfast table.

PMID- 30095115
TI  - Regulation: Treating colleagues with respect.

PMID- 30095118
TI  - Sustainability: Dentists urged to reduce their carbon footprint.

PMID- 30095119
TI  - Large cereal manufacturer cuts sugar content by 40.

PMID- 30095120
TI  - Coronectomy: Coronectomy & CBCT - A marriage of convenience!

PMID- 30095121
TI  - Is detecting oral cancer in general dental practices a realistic expectation? A
      population-based study using population linked data in Scotland.

PMID- 30095122
TI  - New dental imaging centre for Colchester opens.

PMID- 30095123
TI  - Persistent facial pain costs economy $3,000 per year.

PMID- 30095125
TI  - US dental group takes over distribution of American Eagle Instruments.

PMID- 30095124
TI  - Reasons for placement and replacement of crowns in general dental practice.

PMID- 30095126
TI  - Dentists' Annual Retention Fee to stay at current level.

PMID- 30095128
TI  - Health Secretary focus on tech and child obesity.

PMID- 30095129
TI  - Good choice for overdentures.

PMID- 30095130
TI  - Simpler, automated way to switch plan provider.

PMID- 30095131
TI  - More growth for dental corporate.

PMID- 30095132
TI  - Why research?

PMID- 30095133
TI  - Evaluation of the first year of Dental Health Partnerships: a web-based distance
      learning partnership between UK dental educators and students from low-resource
      countries.

PMID- 30095134
TI  - Severe child obesity levels at record high in 10- to 11-year-olds.

PMID- 30095135
TI  - GDC v the dental profession.

PMID- 30095136
TI  - The human iron-proteome.
AB  - Organisms from all kingdoms of life use iron-proteins in a multitude of
      functional processes. We applied a bioinformatics approach to investigate the
      human portfolio of iron-proteins. We separated iron-proteins based on the
      chemical nature of their metal-containing cofactors: individual iron ions, heme
      cofactors and iron-sulfur clusters. We found that about 2% of human genes encode
      an iron-protein. Of these, 35% are proteins binding individual iron ions, 48% are
      heme-binding proteins and 17% are iron-sulfur proteins. More than half of the
      human iron-proteins have a catalytic function. Indeed, we predict that 6.5% of
      all human enzymes are iron-dependent. This percentage is quite different for the
      various enzyme classes. Human oxidoreductases feature the largest fraction of
      iron-dependent family members (about 37%). The distribution of iron proteins in
      the various cellular compartments is uneven. In particular, the mitochondrion and
      the endoplasmic reticulum are enriched in iron-proteins with respect to the
      average content of the cell. Finally, we observed that genes encoding iron
      proteins are more frequently associated to pathologies than the all other human
      genes on average. The present research provides an extensive overview of iron
      usage by the human proteome, and highlights several specific features of the
      physiological role of iron ions in human cells.

PMID- 30095138
TI  - Precise size control of layered double hydroxide nanoparticles through
      reconstruction using tripodal ligands.
AB  - Precise size control of layered double hydroxide nanoparticles (LDHNPs) is
      crucial for their applications in anion exchange, catalysis, and drug delivery
      systems. Here, we report the synthesis of LDHNPs through a reconstruction method,
      using tripodal ligands (e.g., tris(hydroxymethyl)aminomethane; THAM). We found
      that the mechanism of reconstruction at least includes a dissolution
      recrystallization process rather than topotactic transformation. THAM is
      immobilized on the surface of recrystallized LDHNPs with tridentate linkages,
      suppressing their crystal growth especially in lateral directions. The particle
      size of the LDHNPs is precisely controlled by the concentration of THAM
      regardless of the synthetic routes, such as coprecipitation and reconstruction.
      It is suggested that the particle size is controlled on the basis of Ostwald
      ripening which is governed by the equilibrium of the surface modification
      reaction.

PMID- 30095137
TI  - Uptake and accommodation of water clusters by adamantane clusters in helium
      droplets: interplay between magic number clusters.
AB  - We report an experimental study of water clusters as guests in interactions with
      clusters of adamantane (Ad) as hosts that occur in doped helium droplets at
      extremely low temperatures. Separate experiments with pure water as dopant showed
      ready formation of a distribution of water clusters (H2O)mH+ that peaks at m = 11
      and extends beyond m = 100 with local maxima at m = 4, 11, 21, 28 and 30 with
      (H2O)21H+ being the most anomalous and showing the greatest stability with
      respect to clusters immediately adjacent in water content. When adamantane is
      also added as a dopant, extensive hydration is seen in the formation of
      water/adamantane clusters, (H2O)mAdn+; magic number clusters (H2O)21Adn+ are seen
      for all the adamantane clusters. Other magic numbers for water clusters attached
      to adamantane, (H2O)mAdn+, are as for pristine protonated water, with m = 28 and
      m = 30. The icosahedral shell closure of pure adamantane at n = 13 and 19 appears
      to be preserved with (H2O)21 replacing one adamantane. (H2O)21Ad12+ and
      (H2O)21Ad18+ stand out in intensity and demonstrate the interplay of magic number
      water clusters with magic number adamantane clusters, observed perhaps for the
      first time in gas-phase cluster chemistry. There was no clear evidence for the
      formation of clathrate hydrates in which adamantane is trapped within structured
      water.

PMID- 30095139
TI  - Fabrication of selective interface of ZnO/CdS heterostructures for more efficient
      photocatalytic hydrogen evolution.
AB  - In previous studies, photocatalytic heterostructures between two components have
      usually been distributed randomly at the material's surface. It is significant
      and important to fabricate a selective heterostructure interface with more
      efficient charge separation and transfer. In this study, active pores were first
      investigated through competitive adsorption, degradation efficiency, and
      selective corrosion. It was found that selective adsorption-induced
      photosensitization along with active facets led to selective photocorrosion
      around the pores in ZnO nanosheets. Then, comparison between the properties of
      selectively and randomly distributed ZnO/CdS heterostructures is presented,
      namely, phase composition, morphology, pore size, absorbance, electronic band
      structure, photocurrent density, electrochemical impedance, and hydrogen
      evolution. Due to the Z-scheme, ZnO/CdS heterostructure selectively bound at the
      active pores, due to which more efficient charge separation and higher hydrogen
      evolution were achieved for ZnO/CdS-S. Thus, fabrication of selective
      heterostructure interface endows ZnO/CdS with more efficient hydrogen evolution.

PMID- 30095140
TI  - The impact of nitrogen gas flushing on the stability of seasonings: volatile
      compounds and sensory perception of cheese & onion seasoned potato crisps.
AB  - The impact of natural cheese and onion seasoning on the sensory perception and
      shelf life stability of potato crisps was studied. This study was carried out to
      evaluate the impact of nitrogen (N2) gas flushing on the shelf-life stability and
      sensory attributes of cheese & onion seasoned potato crisps. Markers of lipid
      oxidation and flavour volatile compounds were evaluated in sliced, unwashed,
      batch fried potato crisps during accelerated storage at 45  degrees C for 10
      weeks. Volatile flavour compounds were evaluated by headspace gas analysis using
      solid phase microextraction (SPME) GC-MS and correlated with sensory perception.
      Gas flushing significantly increases the shelf life of both unsalted and cheese &
      onion seasoned potato crisps in terms of the stability of volatile compounds and
      sensory perception. Further to this, the addition of the cheese & onion seasoning
      increased the shelf life of the base potato crisp; this is proposed to be
      explained by the antioxidant properties of milk proteins in the seasoning.
      Sensory evaluation indicated that the key negative sensory attributes reported
      were rancidity and stale attributes, which were correlated to the progression of
      lipid oxidation and loss of flavour over storage time irrespective of the
      packaging environment (with/without gas flushing).

PMID- 30095141
TI  - Biotin-tagged fluorescent sensor to visualize 'mobile' Zn2+ in cancer cells.
AB  - A cancer cell-targeting fluorescent sensor has been developed to image mobile
      Zn2+ by introducing a biotin group. It shows a highly selective response to
      Zn2+in vitro, no toxicity in cellulo and images 'mobile' Zn2+ specifically in
      cancer cells. We believe this probe has the potential to help improve our
      understanding of the role of Zn2+ in the processes of cancer initiation and
      development.

PMID- 30095142
TI  - The specific impact of uremic toxins upon cognitive domains: a review.
AB  - One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive
      impairment is the accumulation of uremic toxins due to the deterioration of the
      renal clearance function. Cognition can be categorized into five major domains
      according to its information processing functions: memory, attention, language,
      visual-spatial, and executive. We performed a review using the terms 'uric acid',
      'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and
      'parathyroid hormone'. These are the compounds that were found to be strongly
      associated with cognitive impairment in CKD in the literature. The 26 selected
      articles point towards an association between higher levels of uric acid,
      homocysteine, and interleukin 6 with lower cognitive performance in executive,
      attentional, and memory domains. We also reviewed the hemodialysis effects on
      cognition. Hemodialysis seems to contribute to an amelioration of CKD-related
      encephalopathic dysfunction, although this improvement occurs more in some
      cognitive domains than in others.

PMID- 30095143
TI  - ANCA associated vasculitis: experience of a tertiary care referral center.
AB  - BACKGROUND AND OBJECTIVES: Anti-neutrophil cytoplasmic autoantibodies (ANCA)
      associated vasculitis is a small vessel vasculitis with insufficient
      epidemiologic estimates in the United States. We aimed to determine demographic
      and clinical features of ANCA associated vasculitis patients presenting to a
      large tertiary care referral center in Upstate New York. Design, setting,
      participants, and measurements: A retrospective analysis of cases with pauci
      immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting
      over 11 years was conducted. Outcomes of interest were: demographics, ANCA
      antibody positivity, patient and renal survival, and regional trends. RESULTS:
      986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19
      MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at
      presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine
      was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks),
      with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of
      12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients
      came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 -
      23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing
      (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity
      was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p =
      0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044).
      Thirty-seven of the 41 cases were referred locally, 16 cases were from within a
      15-mile radius of Albany, Schenectady, and Saratoga counties. CONCLUSIONS: ANCA
      vasculitis is associated with end stage renal disease and increased mortality.
      Our study suggests the possibility of higher regional incidence of pauci-immune
      GN in Upstate New York. Further studies should investigate the causes of
      clustering of cases to specific regions.

PMID- 30095144
TI  - Designing Drug Trials for Frailty: ICFSR Task Force 2018.
AB  - To reduce disability and dependence in older adults, frailty may represent an
      appropriate target for intervention. While preventing frailty through lifestyle
      interventions may be the optimal public health approach for many population
      groups, pharmacological approaches will likely be needed for individuals who meet
      frailty criteria or who have comorbid conditions that contribute to and
      complicate the frailty syndrome, and for those who are not compliant with
      lifestyle interventions. Barriers to successful development of drug treatments
      for frailty include variability in how the frailty syndrome is defined, lack of
      agreement on the best diagnostic tools and outcome measures, and the paucity of
      sensitive, reliable, and validated biomarkers. The International Conference on
      Frailty and Sarcopenia Research Task Force met in Miami, Florida, on February 28,
      2018, to consider the status of treatments under development for frailty and
      discuss potential strategies for advancing the field. They concluded that at the
      present time, there may be a more productive regulatory pathway for adjuvant
      treatments or trials targeting specific functional outcomes such as gait speed.
      They also expressed optimism that several studies currently underway may provide
      the insight needed to advance drug development for frailty.

PMID- 30095145
TI  - The Effect of High Dose Vitamin D3 on Physical Performance in Frail Older Adults.
      A Feasibility Study.
AB  - BACKGROUND: Vitamin D deficiency is ubiquitous in frailty but the effectiveness
      of vitamin D supplementation to improve outcomes in frail individuals is unclear.
      It has been postulated that higher than the current recommended doses (800
      IU/day) may be needed to achieve a neuromuscular effect in frail individuals.
      OBJECTIVES: 1) determine if 4000 IU per day of vitamin D3 is safe for frail older
      adults; and 2) establish the efficacy of this dose to improve physical
      performance outcomes in this population. DESIGN: Open-label, feasibility study.
      SETTING: Community retirement centre. PARTICIPANTS: 40 older adults with frail or
      pre-frail characteristics. INTERVENTION: 4000 IU of vitamin D3 and 1200 mcg of
      calcium carbonate daily for four months. MEASUREMENTS: Physical performance (grip
      strength, gait speed and short physical performance battery score), cognitive
      health and vitamin D and iPTH serum levels before and after the intervention.
      RESULTS: Frail individuals improved short physical performance battery score
      (1.19, p = 0.005), fast gait speed (4.65, p = 0.066) and vitamin D levels (7.81,
      p = 0.011). Only frail females made a significant improvement in grip strength
      (1.92, p = 0.003). Stratifying the sample by baseline vitamin D levels revealed
      that participants with vitamin D insufficiency (<= 75 nmol/L) significantly
      improved short physical performance battery score (1.06, p = 0.04), fast gait
      speed (6.28, p = 0.004) and vitamin D levels (25.73, p = <0.0001). Pre-frail
      individuals, as well as those with sufficient vitamin D levels (> 75 nmol/L) made
      no significant improvement in any outcome. CONCLUSIONS: Vitamin D supplementation
      using 4000 IU/daily is safe and has a modest beneficial effect on physical
      performance for frail individuals and those with insufficient vitamin D levels.
      Participants with vitamin D insufficiency (<= 75 nmol/L) showed greater benefits.
      Our feasibility study provides results to help calculate effect size for a future
      RCT.

PMID- 30095146
TI  - Examining Differences in Recovery Outcomes between Male and Female Hip Fracture
      Patients: Design and Baseline Results of a Prospective Cohort Study from the
      Baltimore Hip Studies.
AB  - BACKGROUND: Incidence of hip fractures in men is expected to increase, yet little
      is known about consequences of hip fracture in men compared to women. It is
      important to investigate differences at time of fracture using the newest
      technologies and methodology regarding metabolic, physiologic, neuromuscular,
      functional, and clinical outcomes, with attention to design issues for recruiting
      frail older adults across numerous settings. OBJECTIVES: To determine whether at
      least moderately-sized sex differences exist across several key outcomes after a
      hip fracture. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study
      (Baltimore Hip Studies 7th cohort [BHS-7]) was designed to include equal numbers
      of male and female hip fracture patients to assess sex differences across various
      outcomes post-hip fracture. Participants were recruited from eight hospitals in
      the Baltimore metropolitan area within 15 days of admission and were assessed at
      baseline, 2, 6 and 12 months post-admission. MEASUREMENTS: Assessments included
      questionnaire, functional performance evaluation, cognitive testing, measures of
      body composition, and phlebotomy. RESULTS: Of 1709 hip fracture patients screened
      from May 2006 through June 2011, 917 (54%) were eligible and 39% (n=362) provided
      informed consent. The final analytic sample was 339 (168 men and 171 women). At
      time of fracture, men were sicker (mean Charlson score= 2.4 vs. 1.6; p<0.001) and
      had worse cognition (3MS score= 82.3 vs. 86.2; p<0.05), and prior to fracture
      were less likely to be on bisphosphonates (8% vs. 39%; p<0.001) and less
      physically active (2426 kilocalories/week vs. 3625; p<0.001). CONCLUSIONS: This
      paper provides the study design and methodology for recruiting and assessing hip
      fracture patients and evidence of baseline and pre-injury sex differences which
      may affect eventual recovery one year later.

PMID- 30095147
TI  - Spousal Caregiving Is Associated with an Increased Risk of Frailty: A Case
      Control Study.
AB  - BACKGROUND: Evidence suggests that providing care for a disabled elderly person
      may have implications for the caregiver's own health (decreased immunity,
      hypertension, and depression). OBJECTIVE: Explore if older spousal caregivers are
      at greater risks of frailty compared to older people without a load of care.
      DESIGN: Case-control study. SETTING: Participants were assessed at home in
      Wallonia, Belgium. PARTICIPANTS: Cases: community-dwelling spousal caregivers of
      older patients, recruited mainly by the geriatric outpatient clinic. CONTROLS:
      people living at home with an independent spouse at the functional and cognitive
      level matched for age, gender and comorbidities. MEASUREMENTS: Mini nutritional
      assessment-short form (MNA-SF), short physical performance battery (SPPB),
      frailty phenotype (Fried), geriatric depression scale (GDS-15), clock drawing
      test, sleep quality, and medications. The multivariable analysis used a
      conditional logistic regression. RESULTS: Among 79 caregivers, 42 were women;
      mean age and Charlson comorbidity index were 79.4+/-5.3 and 4.0+/-1.2,
      respectively. Among care-receivers (mean age 81.4+/-5.2), 82% had cognitive
      impairment. Caregiving was associated with a risk of frailty (Odd Ratio (OR)
      6.66; 95% confidence interval (CI) 2.20-20.16), the consumption of
      antidepressants (OR 4.74; 95% CI 1.32 -17.01), shorter nights of sleep (OR 3.53;
      95% CI 1.37-9.13) and more difficulties maintaining a social network (OR 5.25;
      95% CI 1.68-16.40). CONCLUSIONS: Spousal caregivers were at an increased risk of
      being frail, having shorter nights of sleep, taking antidepressants and having
      difficulties maintaining their social network, compared to non-caregiver
      controls. Older spousal caregivers deserve the full attention of professionals to
      prevent functional decline and anticipate a care breakdown.

PMID- 30095148
TI  - Subjective Sleep Quality among Sarcopenic and Non-Sarcopenic Older Adults:
      Results from the SarcoPhAge Cohort.
AB  - BACKGROUND: It seems that sleep quality could impact the physiological process
      related to loss of muscle mass. OBJECTIVES: We seek to compare subjective sleep
      quality of sarcopenic and non-sarcopenic subjects diagnosed according to 6
      definitions. DESIGN: Cross-sectional data used in this analysis were collected
      from the SarcoPhAge (Sarcopenia and Physical Impairment with Advancing Age)
      cohort, a prospective study aiming to assess clinical parameters linked to
      sarcopenia. PARTICIPANTS: The present study was interested in communitydwelling
      older adults with and without sarcopenia. Measurements - A diagnosis of
      sarcopenia was established according to 6 definitions. Three assessments were
      carried out: an evaluation of lean mass, a measurement of muscle strength and an
      assessment of physical performance. In addition, to evaluate the parameters of
      subjective sleep, we used the Pittsburgh Sleep Quality Index (PSQI), a self
      administered questionnaire evaluating 7 components of sleep architecture.
      RESULTS: A total of 255 individuals aged 74.7+/-5.8 years were included. Based on
      the 6 different definitions, the prevalence of sarcopenia ranged from 5.9% to
      32.5%. There was no significant difference between sarcopenic and non-sarcopenic
      subjects regarding most of the components of subjective sleep quality. However,
      the definition of Cruz-Jentoft et al. (2010) indicated that sarcopenic subjects
      had higher scores than non-sarcopenic subjects for two components: sleep latency
      and day-time dysfunction (p=0.03 and p=0.04, adjusted for confounders). Moreover,
      some parameters of sleep quality were correlated with components of sarcopenia.
      CONCLUSIONS: Some properties of subjective sleep quality seem to be associated
      with sarcopenia and seem correlated with at least one of the three components of
      the condition.

PMID- 30095149
TI  - Congregate Meals: Opportunities to Help Vulnerable Older Adults Achieve Diet and
      Physical Activity Recommendations.
AB  - BACKGROUND: Through diet and exercise interventions, community centers offer an
      opportunity to address health-related issues for some of the oldest, most
      vulnerable members of our society. OBJECTIVES: The purpose of this investigation
      is to draw upon nationwide data to better characterize the population served by
      the congregate meals program and to gather more detailed information on a local
      level to identify opportunities for service enhancement to improve the health and
      well-being of older adults. DESIGN: We examined community center data from two
      sources: 2015 National Survey of Older Americans Act and surveys from two New
      York City community centers. To assess nationwide service delivery, we analyzed
      participant demographics, functional status defined by activities of daily
      living, and perceptions of services received. MEASUREMENTS: Participants from the
      two New York City community centers completed a four-day food record. Functional
      measures included the short physical performance battery, self-reported physical
      function, grip strength, and the Montreal Cognitive Assessment. RESULTS:
      Nationwide (n=901), most participants rated the meal quality as good to excellent
      (91.7%), and would recommend the congregate meals program to a friend (96.0%).
      Local level data (n=22) were collected for an in-depth understanding of diet,
      physical activity patterns, body weight, and objective functional status
      measures. Diets of this small, local convenience sample were higher in fat,
      cholesterol, and sodium, and lower in calcium, magnesium, and fiber than
      recommended by current United States Dietary Guidelines. Average time engaged in
      moderate physical activity was 254 minutes per week (SD=227), exceeding the
      recommended 150 minutes per week, but just 41% (n=9) and 50% (n=11) of
      participants engaged in strength or balance exercises, respectively. CONCLUSION:
      Research is warranted to test whether improvements in the nutritional quality of
      food served and access/supports for engaging in strength training within
      community centers could help older adults achieve diet and physical activity
      recommendations.

PMID- 30095151
TI  - Older People Who Are Frequent Users of Acute Care: A Symptom of Fragmented Care?
      A Case Series Report on Patients' Pathways of Care.
AB  - Older frequent users of acute care can experience fragmented care. There is a
      need to understand the issues in a local context before attempting to address
      fragmented care. 0.5% (n=61) of the population in a defined local government area
      were identified as having >=4 unplanned emergency department (ED) presentations/
      admissions to an acute-care hospital over 13 months. A retrospective case-series
      study was conducted to examine detailed pathways of care for 17 patients within
      the identified population. The two dominant presentation reasons were clinical
      symptoms associated with a declining/significant loss of capacity in fundamental
      self-care activities and chronic cardiac/respiratory conditions. Of patients
      discharged home, 21% of discharge letters were delayed >7 days and only 19%
      received a written discharge plan. Half of community dwelling patients received
      home nursing and/or assistance. Frequent users of acute care can experience
      untimely hospital communication and may require more coordinated care provided in
      the community to assist self-care and manage chronic conditions.

PMID- 30095150
TI  - Development of the Nutrition and Functionality Assessment (NFA) among Older
      Adults in Japan.
AB  - OBJECTIVE: Develop and evaluate the feasibility and validity of the Nutrition and
      Functionality Assessment (NFA) which identifies "target" older adults who could
      benefit from a personalized program following evaluation of their nutrition
      status and physical functionality. DESIGN: Cross-sectional study. SETTING:
      Community and geriatric day-care centers and university in Japan. PARTICIPANTS:
      267 older adults aged 65-90. MEASUREMENTS: The "target" individuals were screened
      based on gait speed (0.6-1.5 m/s). Nutrition (Mini Nutrition Assessment-short
      form and protein intake), strength (30s chair sit-to-stand and hand-grip
      strength) and endurance (6-minute walk) were assessed. Physical activity was
      monitored using a tri-axil accelerometer for a week. Fried frailty phenotype was
      also assessed. RESULTS: Out of 267 individuals, 185 (69%) had gait speed between
      0.6-1.5 m/s, corresponding to our "target" group from which, 184 (95%) completed
      the nutrition and physical functionality assessments with the physical activity
      monitoring. The NFA was completed in approximately 30 minutes. No adverse events
      directly due to the NFA were reported. NFA physical functionality and global
      scores were significantly related to frailty phenotype but nutrition score was
      not related to frailty phenotype. CONCLUSION: The study demonstrated that the NFA
      is a safe and feasible tool to screen target older adults and simultaneously
      evaluate their nutritional status and physical functionality. Validity of the NFA
      was partially confirmed by the significant association of the global and physical
      functionality scores with frailty phenotype. More studies are required to
      validate and maximize the applicability of the NFA in communities and
      institutions in Japan and elsewhere.

PMID- 30095152
TI  - Nutritional Status in Frail Cirrhotic Patients Undergoing Liver Transplantation.

PMID- 30095153
TI  - Feasibility of Weighted Vest Use during a Dietary Weight Loss Intervention and
      Effects on Body Composition and Physical Function in Older Adults.
AB  - BACKGROUND: While intentional weight loss in older adults with obesity yields
      clinically important health benefits there is a need to minimize the negative
      effects of weight loss on concomitant loss of muscle mass and strength. Data show
      wearing weighted vests during exercise improves lean mass and lower extremity
      strength, however the efficacy of wearing a weighted vest during a period of
      weight loss to mitigate muscle and strength loss is not known. OBJECTIVES: This
      study examined the feasibility of daily weighted vest use during a dietary weight
      loss intervention, and examined effects of vest use on body composition and
      physical function in well-functioning older adults with obesity. DESIGN:
      Randomized, controlled pilot study. SETTING: Wake Forest Baptist Medical Center
      in Winston-Salem, NC. PARTICIPANTS: 37 older (age=65-79 yrs), obese (BMI=30-40
      kg/ m2) sedentary men and women. INTERVENTIONS: 22-week behavioral diet
      intervention (targeting 10% weight loss, 1100-1300 kcals/day) with (Diet+Vest;
      n=20) or without (Diet; n=17) weighted vest use (goal of 10 hours/ day with
      weight added weekly according to individual loss of body mass). MEASUREMENTS:
      Body composition by dual-energy x-ray absorptiometry and measures of physical
      function, mobility, and muscle strength/power. RESULTS: Average weighted vest use
      was 6.7+/-2.2 hours/day and the vest-wear goal of 10 hrs/day was achieved for
      67+/-22% of total intervention days. Five participants reported adverse events
      from wearing the vest (all back pain or soreness). Both groups lost a similar
      amount of weight (Diet= -11.2+/-4.4 kg; Diet+Vest = -11.0+/-6.3 kg; p<0.001),
      with no differences between groups (p=0.25). Fat mass, lean mass, and % body fat
      decreased significantly (p<0.0001), with no differences between groups. Compared
      to Diet+Vest, the Diet intervention resulted in greater decreases in leg power
      (p<0.02), with no other between group differences in physical function.
      CONCLUSION: This pilot study showed that vest use during dietary weight loss is
      feasible and safe in well-functioning older adults with obesity. Larger studies
      are needed to definitively determine whether external replacement of lost weight
      during caloric restriction may preserve lower extremity muscle strength and
      power.

PMID- 30095154
TI  - Incidence and outcomes of lymphoid malignancies in adolescent and young adult
      patients in the United States.
AB  - Lymphoma incidence and survival in adolescent and young adult (AYA, defined as 15
      39 years of age) and adult patients (>39 years) were assessed using Surveillance,
      Epidemiology, and End Results (SEER) data. From 2000 to 2014, 431 721 lymphoma
      cases were reported to SEER, 9% in AYA patients. In the AYA group, the highest
      age-adjusted incidence rate was for classical Hodgkin lymphoma [HL; 3.4 per 100
      000 person-years; 95% confidence interval (CI), 3.38-3.49] followed by diffuse
      large B cell lymphoma (DLBCL; 1.56, 95% CI, 1.53-1.60) and for adults, it was
      plasma cell neoplasms (14.17, 95% CI, 14.07-14.27), DLBCL (13.86, 95% CI, 13.76
      13.96) and chronic lymphocytic leukaemia (CLL; 13.19, 95% CI, 13.09-13.29). HL
      comprised 42% of lymphoma cases for AYAs, but only 4% in adults. The occurrence
      of DLBCL among AYAs and adults was similar, 18% and 20%, respectively. Twenty
      eight percent of AYAs compared with 9% of adults presented with stage II disease,
      and 21% of AYAs compared with 10% of adults had B-symptoms. Extranodal disease
      was less common (33%) in AYAs than adults (59%). Overall, AYA patients with
      lymphoma have better 2- and 5-year relative survival rates (RSRs) compared to
      adults. When restricted to HL and DLBCL, RSR of AYA patients exceeds adult RSR.

PMID- 30095155
TI  - Antagonistic pleiotropy for carbon use is rare in new mutations.
AB  - Pleiotropic effects of mutations underlie diverse biological phenomena such as
      ageing and specialization. In particular, antagonistic pleiotropy ("AP": when a
      mutation has opposite fitness effects in different environments) generates
      tradeoffs, which may constrain adaptation. Models of adaptation typically assume
      that AP is common - especially among large-effect mutations - and that
      pleiotropic effect sizes are positively correlated. Empirical tests of these
      assumptions have focused on de novo beneficial mutations arising under strong
      selection. However, most mutations are actually deleterious or neutral, and may
      contribute to standing genetic variation that can subsequently drive adaptation.
      We quantified the incidence, nature, and effect size of pleiotropy for carbon
      utilization across 80 single mutations in Escherichia coli that arose under
      mutation accumulation (i.e., weak selection). Although ~46% of the mutations were
      pleiotropic, only 11% showed AP; among beneficial mutations, only ~4% showed AP.
      In some environments, AP was more common in large-effect mutations; and AP effect
      sizes across environments were often negatively correlated. Thus, AP for carbon
      use is generally rare (especially among beneficial mutations); is not
      consistently enriched in large-effect mutations; and often involves weakly
      deleterious antagonistic effects. Our unbiased quantification of mutational
      effects therefore suggests that antagonistic pleiotropy may be unlikely to cause
      maladaptive tradeoffs.

PMID- 30095156
TI  - Body size, developmental instability, and climate change.
AB  - Development is often temperature-dependent. We hypothesized smaller size and
      larger asymmetry with increasing temperatures. However, we also predicted
      associations with asymmetry to differ among traits that differ in their degree of
      functional importance (especially the functional wings in migratory birds were
      predicted to be more canalized), timing of development (skeletal [femur, tarsus,
      and humerus] vs. feather [wing and tail traits]). We analyzed a large dataset of
      which we included species with at least 20 specimens resulting in 5533 asymmetry
      values in 1593 individuals from 66 species. There was a consistent significant
      decrease in size with temperature across all traits. Fluctuating asymmetry (FA)
      for wings and femur was on average lower, suggesting higher canalization, and it
      decreased with migration distance, however that was not the case for the other
      traits. FA increased with increasing temperature for wings, but not for the other
      characters, where the different responses of different characters to temperature
      were significant. Because there was no significant three-way interaction between
      temperature, migration distance, and character, the asymmetry-temperature
      response was similar in migratory and resident species. These findings imply that
      climate warming reduces size of all traits and decreases developmental
      instability of wings in birds.

PMID- 30095157
TI  - Inflammatory mediators: a causal link to hypertension during preeclampsia.
AB  - Preeclampsia (PE) is a hypertensive disorder that occurs after 20 weeks of
      gestation, implicating the placenta as a key offender. PE is associated with an
      imbalance among B lymphocytes, CD4+ T lymphocytes, NK cells and increased
      inflammatory cytokines. During early onset PE, trophoblast invasion and
      placentation are impaired, leading to reduced blood flow to the fetus. In all
      spectrums of this disorder, a shift towards a pro-inflammatory state where
      regulatory cells and cytokines are decreased occurs. Specifically, inflammatory
      CD4+ T-cells and inflammatory cytokines are increased while CD4+ T regulatory
      cells (Tregs) and immunosuppressive cytokines such as IL-4 and IL-10 are
      decreased resulting in B cell activation, production of autoantibodies,
      endothelial dysfunction and hypertension associated with PE. However, the
      stimulus for these imbalances is unknown and need to be fully understood so that
      effective treatments that target the pathogenesis of the disease can be designed.
      Therefore, this review will focus on the pathways involving CD4+ , TH1, TH2,
      Tregs, TH17s, B cells, and NK cells in the pathophysiology of PE.

PMID- 30095159
TI  - Rational Suicide in Older Adults: Not an Ageist Concept by Default.

PMID- 30095158
TI  - Validation of the MCL35 gene expression proliferation assay in randomized trials
      of the European Mantle Cell Lymphoma Network.
AB  - Mantle cell lymphoma (MCL) is still considered incurable and the course of the
      disease is highly variable. Established risk factors include the Mantle Cell
      Lymphoma International Prognostic Index (MIPI) and the quantification of the
      proliferation rate of the tumour cells, e.g. by Ki-67 immunohistochemistry. In
      this study, we aimed to validate the prognostic value of the gene expression
      based MCL35 proliferation assay in patient cohorts from randomized trials of the
      European Mantle Cell Lymphoma Network. Using this assay, we analysed the gene
      expression proliferation signature in routine diagnostic lymph node specimens
      from MCL Younger and MCL Elderly trial patients, and the calculated MCL35 score
      was used to assign MCL patients to low (61%), standard (27%) or high (12%) risk
      groups with significantly different outcomes. We confirm here in our prospective
      clinical trial cohort of MCL patients, that the MCL35 assay is strongly
      prognostic, providing additional information to the Ki-67 index and the MIPI.
      Thus, this robust assay may assist in making treatment decisions or in devising
      risk-adapted prospective clinical trials in the future.

PMID- 30095160
TI  - Venous thromboembolic risk assessment in pregnancy: comparison of the All-Wales
      maternity risk assessment tool with guidance from the Royal College of Obstetrics
      and Gynaecology.

PMID- 30095161
TI  - Real world outcomes of pomalidomide for treatment of relapsed light chain
      amyloidosis.
AB  - Pomalidomide is a next-generation immunomodulatory agent with activity in
      relapsed light chain (AL) amyloidosis, but real world outcomes are lacking. We
      report the experience of the UK National Amyloidosis Centre. All patients with AL
      amyloidosis treated with pomalidomide between 2009 and 2017 were included. Data
      was collected on treatment toxicity and clonal response. Survival was calculated
      by the Kaplan-Meier method and outcomes reported on an intent-to-treat (ITT)
      basis. A total of 29 patients treated with pomalidomide were identified.
      Haematological responses at 3 months were: complete response (CR) nil, very good
      partial response (VGPR) 10 (35%), partial response (PR) 9 (31%), stable or
      progressive disease 7 (24%), unevaluable 3 (10%). On an ITT basis (n = 28),
      responses at 6 months were: CR- nil, VGPR-11 (39%), PR-2 (7%) and the remaining
      patients were non-responders 15 (53%). Median overall survival was 27 months (95%
      confidence interval 15.7-38.1 months). Median progression free survival (PFS) was
      15 months (95% confidence interval 6.24-23.77). In conclusion, pomalidomide has
      activity in patients with relapsed AL amyloidosis. Responses are rapid and early
      responses may be predictive of a sustained overall response. Deep responses (VGPR
      or better) are seen in only a third of all patients and combination therapy needs
      to be explored.

PMID- 30095162
TI  - An overview of 25 years of incidence, treatment and outcome of colorectal cancer
      patients.
AB  - Regarding the continuous changes in the diagnostic process and treatment of
      colorectal cancer (CRC), it is important to evaluate long-term trends which are
      relevant in giving direction for further research and innovations in cancer
      patient care. The aim of this study was to analyze developments in incidence,
      treatment and survival for patients diagnosed with CRC in the Netherlands. For
      this population-based retrospective cohort study, all patients diagnosed with CRC
      between 1989 and 2014 in the Netherlands were identified using data of the
      nationwide population-based Netherlands Cancer Registry (n = 267,765), with
      follow-up until January 1, 2016. Analyses were performed for trends in incidence,
      mortality, stage distribution, treatment and relative survival measured from the
      time of diagnosis. The incidence of both colon and rectal cancer has risen. The
      use of postoperative chemotherapy for Stage III colon cancer increased (14-60%),
      as well as the use of preoperative (chemo)radiotherapy for rectal cancer (2-66%).
      The administration of systemic therapy and metastasectomy increased for Stage IV
      disease patients. The 5-year relative survival increased significantly from 53 to
      62% for colon cancer and from 51 to 65% for rectal cancer. Ongoing advancements
      in treatment, and also improvement in other factors in the care of CRC patients
      such as diagnostics, dedicated surgery and pre- and postoperative care-lead to a
      continuous improvement in the relative survival of CRC patients. The increasing
      incidence of CRC favors the implementation of the screening program, of which the
      effects should be monitored closely.

PMID- 30095163
TI  - Sleep and Migraine: Assessment and Treatment of Comorbid Sleep Disorders.
AB  - The relationship of sleep and migraine is unequivocal and familiarity with the
      nature and magnitude of these associations may inform clinical practice. Recent
      prospective, longitudinal, and time-series analysis has begun to unravel the
      magnitude and temporal patterns of sleep and migraine. Prospective evidence has
      shown that sleep variables can trigger acute migraine, precede and predict new
      onset headache by several years, and indeed, sleep disturbance and snoring are
      risk factors for chronification. The presence of a sleep disorder is associated
      with more frequent and severe migraine and portends a poorer headache prognosis.
      Interestingly, the disorders linked to migraine are quite varied, including
      insomnia, snoring and obstructive sleep apnea, restless legs, circadian rhythm
      disorders, narcolepsy, and others. Insomnia is by far the most common sleep
      disorder in headache patients. In fact, the majority of patients with chronic
      migraine presenting for treatment have insomnia. Despite a rapidly expanding
      literature, very few controlled treatment studies have been published to guide
      clinical practice. This paper focuses on clinical assessment and treatment of
      sleep disorders. An algorithm is presented for sleep disorders management in the
      migraine patient, which highlights major sleep disorders and psychiatric
      comorbidity. Diagnostic procedures are recommended that are conducive to clinical
      practice. Suggested tools include the sleep history, screening mnemonics,
      prediction equation, and sleep diary. New developments in treatment have produced
      abbreviated and cost-effective therapies for insomnia and obstructive sleep apnea
      that may reach a larger population. Revisions in the diagnostic manuals for sleep
      and headache disorders enhance recognition of sleep-related headache.
      Recommendations include behavioral sleep regulation, shown in recent controlled
      trials to decrease migraine frequency, management for sleep apnea headache,
      cognitive behavioral therapy (CBT) for insomnia abbreviated for the physician
      practice setting, sleep-related headache trigger, and others. There is no
      empirical evidence that sleep evaluation should delay or supersede usual headache
      care. Rather, sleep management is complimentary to standard headache practice.

PMID- 30095165
TI  - Mating consequences of contrasting hermaphroditic plant sexual systems.
AB  - For hermaphroditic angiosperms with multiple flowers, the sex roles can be
      exclusively combined in bisexual flowers (monocliny), strictly separated among
      different flowers (monoecy), or arrayed in mixtures of bisexual flowers with
      female flowers (gynomonoecy) or male flowers (andromonoecy). The hypothesized
      benefits favoring the evolution of these contrasting hermaphroditic sexual
      systems are typically examined individually, usually by assessing success through
      only one sex role. We tested predictions of most hypotheses experimentally with
      an andromonoecious species, Anticlea occidentalis (Melanthiaceae), based on the
      performance of intact plants (andromonoecy) and those with emasculated bisexual
      flowers (functionally monoecious) or emasculated male flowers (functionally
      monoclinous with sterile peripheral flowers). Andromonoecy in this species
      enables efficient, size-dependent resource allocation, emphasizing female
      function in large plants. Emasculation revealed that anthers in male flowers
      promote female mating quality (outcrossing rate and mate diversity), whereas
      anthers in bisexual flowers promote male mating quantity (pollen dispersal
      distance and probability of any siring success). Thus, different hermaphroditic
      sexual systems likely evolve to capitalize on suites of benefits, rather than
      just one, and provide compromises between quantitative and qualitative
      reproductive components. These compromises apparently maximize an individual's
      combined genetic contributions through female and male functions, rather than
      separate contributions through each sex role.

PMID- 30095164
TI  - Fatigue-related group III/IV muscle afferent feedback facilitates intracortical
      inhibition during locomotor exercise.
AB  - KEY POINTS: This study investigated the influence of group III/IV muscle
      afferents on corticospinal excitability during cycling exercise and focused on
      GABAB neuron-mediated inhibition as a potential underlying mechanism. The study
      provides novel evidence to demonstrate that group III/IV muscle afferent feedback
      facilitates inhibitory intracortical neurons during whole body exercise. Firing
      of these interneurons probably contributes to the development of central fatigue
      during physical activity. ABSTRACT: We investigated the influence of group III/IV
      muscle afferents in determining corticospinal excitability during cycling
      exercise and focused on GABAB neuron-mediated inhibition as a potential
      underlying mechanism. Both under control conditions (CTRL) and with lumbar
      intrathecal fentanyl (FENT) impairing feedback from group III/IV leg muscle
      afferents, subjects (n = 11) cycled at a comparable vastus-lateralis EMG signal
      (~0.26 mV) before (PRE; 100 W) and immediately after (POST; 90 +/- 2 W) fatiguing
      constant-load cycling exercise (80% Wpeak; 221 +/- 10 W; ~8 min). During, PRE and
      POST cycling, single and paired-pulse (100 ms interstimulus interval)
      transcranial magnetic stimulations (TMS) were applied to elicit unconditioned and
      conditioned motor-evoked potentials (MEPs), respectively. To distinguish between
      cortical and spinal contributions to the MEPs, cervicomedullary stimulations
      (CMS) were used to elicit unconditioned (CMS only) and conditioned (TMS+CMS, 100
      ms interval) cervicomedullary motor-evoked potentials (CMEPs). While
      unconditioned MEPs were unchanged from PRE to POST in CTRL, unconditioned CMEPs
      increased significantly, resulting in a decrease in unconditioned MEP/CMEP (P <
      0.05). This paralleled a reduction in conditioned MEP (P < 0.05) and no change in
      conditioned CMEP. During FENT, unconditioned and conditioned MEPs and CMEPs were
      similar and comparable during PRE and POST (P > 0.2). These findings reveal that
      feedback from group III/IV muscle afferents innervating locomotor muscle
      decreases the excitability of the motor cortex during fatiguing cycling exercise.
      This impairment is, at least in part, determined by the facilitating effect of
      these sensory neurons on inhibitory GABAB intracortical interneurons.

PMID- 30095167
TI  - A latent state-trait model for analyzing states, traits, situations, method
      effects, and their interactions.
AB  - OBJECTIVE: Studies on situation and Person * Situation interaction effects often
      use only one method of measurement, so that the extent to which the effects may
      be method-specific cannot be determined. We introduce a new multimethod latent
      state-trait model for random and fixed situations (MM-LST-RF), which allows
      examining person, situation, and Person * Situation interaction effects in the
      context of multimethod measurement designs (e.g., studies with multiple
      reporters), and discuss potential areas of application for the new model in
      personality research. METHOD: The new model allows analyzing novel features of
      multimethod, multi-situation data, including (a) the convergent validity and
      method specificity of trait (person) effects, situation effects, and Person *
      Situation interaction effects; (b) the degree of situation specificity of method
      effects; and (c) potential Method * Situation interactions. An application to
      smoker's affect (N = 235; 57% female; 93% Caucasian) before and after quitting
      smoking is presented with positively and negatively worded items as methods.
      RESULTS: The MM-LST-RF model fit the smoking data well. Method specificity of
      many effects was high. CONCLUSIONS: The MM-LST-RF model provides researchers with
      a new framework for testing method specificity of person, situation, and
      interaction effects.

PMID- 30095166
TI  - Plant odor and sex pheromone are integral elements of specific mate recognition
      in an insect herbivore.
AB  - Specific mate recognition relies on the chemical senses in most animals, and
      especially in nocturnal insects. Two signal types mediate premating olfactory
      communication in terrestrial habitats: sex pheromones, which blend into an
      atmosphere of plant odorants. We show that host plant volatiles affect the
      perception of sex pheromone in males of the African cotton leafworm Spodoptera
      littoralis and that pheromone and plant volatiles are not perceived as
      independent messages. In clean air, S. littoralis males are attracted to single
      synthetic pheromone components or even the pheromone of a sibling species,
      oriental cotton leafworm S. litura. Presence of host plant volatiles, however,
      reduces the male response to deficient or heterospecific pheromone signals. That
      plant cues enhance discrimination of sex pheromone quality confirms the idea that
      specific mate recognition in noctuid moths has evolved in concert with adaptation
      to host plants. Shifts in either female host preference or sex pheromone
      biosynthesis give rise to new communication channels that have the potential to
      initiate or contribute to reproductive isolation.

PMID- 30095168
TI  - Home parenteral nutrition for people with inoperable malignant bowel obstruction.
AB  - BACKGROUND: People with advanced ovarian or gastrointestinal cancer may develop
      malignant bowel obstruction (MBO). They are able to tolerate limited, if any,
      oral or enteral (via a tube directly into the gut) nutrition. Parenteral
      nutrition (PN) is the provision of macronutrients, micronutrients, electrolytes
      and fluid infused as an intravenous solution and provides a method for these
      people to receive nutrients. There are clinical and ethical arguments for and
      against the administration of PN to people receiving palliative care. OBJECTIVES:
      To assess the effectiveness of home parenteral nutrition (HPN) in improving
      survival and quality of life in people with inoperable MBO. SEARCH METHODS: We
      searched the following electronic databases: Cochrane Central Register of
      Controlled Trials (CENTRAL; 2018, Issue 1), MEDLINE (Ovid), Embase (Ovid), BNI,
      CINAHL, Web of Science and NHS Economic Evaluation and Health Technology
      Assessment up to January 2018, ClinicalTrials.gov (http://clinicaltrials.gov/)
      and in the World Health Organization (WHO) International Clinical Trials Registry
      Platform (ICTRP) search portal (http://apps.who.int/trialsearch/). In addition,
      we handsearched included studies and used the 'Similar articles' feature on
      PubMed for included articles. SELECTION CRITERIA: We included any studies with
      more than five participants investigating HPN in people over 16 years of age with
      inoperable MBO. DATA COLLECTION AND ANALYSIS: We extracted the data and assessed
      risk of bias for each study. We entered data into Review Manager 5 and used
      GRADEpro to assess the quality of the evidence. MAIN RESULTS: We included 13
      studies with a total of 721 participants in the review. The studies were
      observational, 12 studies had only one relevant treatment arm and no control and
      for the one study with a control arm, very few details were given. The risk of
      bias was high and the certainty of evidence was graded as very low for all
      outcomes. Due to heterogeneity of data, meta-analysis was not performed and
      therefore the data were synthesised via a narrative summary.The evidence for
      benefit derived from PN was very low for survival and quality of life. All the
      studies measured overall survival and 636 (88%) of participants were deceased at
      the end of the study. However there were varying definitions of overall survival
      that yielded median survival intervals between 15 to 155 days (range three to
      1278 days). Three studies used validated measures of quality of life. The results
      from assessment of quality of life were equivocal; one study reported
      improvements up until three months and two studies reported approximately similar
      numbers of participants with improvements and deterioration. Different quality of
      life scales were used in each of the studies and quality of life was measured at
      different time points. Due to the very low certainty of the evidence, we are very
      uncertain about the adverse events related to PN use. Adverse events were
      measured by nine studies and data for individual participants could be extracted
      from eight studies. This revealed that 32 of 260 (12%) patients developed a
      central venous catheter infection or were hospitalised because of complications
      related to PN. AUTHORS' CONCLUSIONS: We are very uncertain whether HPN improves
      survival or quality of life in people with MBO as the certainty of evidence was
      very low for both outcomes. As the evidence base is limited and at high risk of
      bias, further higher-quality prospective studies are required.

PMID- 30095169
TI  - Effect of Medicare Part D on Ethnoracial Disparities in Antidementia Medication
      Use.
AB  - OBJECTIVES: To examine ethnoracial disparities in antidementia medication use,
      accounting for implementation of Part D, and to evaluate the role of prescription
      drug coverage as a cause of antidementia medication disparities. DESIGN: Rotating
      panel of Medicare beneficiaries who participated in the Medicare Current
      Beneficiary Survey from 2003 to 2013. SETTING: Nationally representative sample
      of Medicare fee-for-service (FFS) beneficiaries with dementia. PARTICIPANTS:
      Community-dwelling FFS Medicare beneficiaries with dementia (N=4,304).
      MEASUREMENTS: Antidementia medication use, defined as at least one prescription
      fill in a given year. RESULTS: Unadjusted antidementia medication use was 10
      percentage points lower for ethnoracial minority beneficiaries before Part D was
      implemented in 2006 (p=.01). This difference was attenuated after adjusting for
      demographic and socioeconomic factors (6-percentage points; p=.10). Part D was
      associated with a 6-percentage point increase in use (p<.01). The increase in use
      associated with Part D was higher although not statistically significantly so in
      ethnoracial minority beneficiaries (8-percentage points, p=.08). Analyses of each
      ethnoracial group found a significant effect of Part D only in Hispanic/Latino
      beneficiaries (18-percentage points; p<.01, adjusted). CONCLUSION: Antidementia
      medication disparities were reduced with expanded prescription drug coverage
      through Medicare Part D. Increases in antidementia medication use for minority
      beneficiaries started after Part D was implemented, with the largest increases in
      use observed in Hispanic/Latino beneficiaries.

PMID- 30095170
TI  - Surgery versus thrombolysis for initial management of acute limb ischaemia.
AB  - BACKGROUND: Both peripheral arterial thrombolysis and surgery can be used in the
      management of peripheral arterial ischaemia. Much is known about the indications,
      risks, and benefits of thrombolysis. However, whether thrombolysis works better
      than surgery for initial management of acute limb ischaemia remains unknown. This
      is the second update of the review first published in 2002. OBJECTIVES: To
      determine whether thrombolysis or surgery is the more effective technique in the
      initial management of acute limb ischaemia due to thromboembolism. SEARCH
      METHODS: For this update, the Cochrane Vascular Information Specialist (CIS)
      searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE Ovid,
      Embase Ovid, CINAHL, AMED, and clinical trials registries up to 7 May 2018.
      SELECTION CRITERIA: All randomised controlled studies comparing thrombolysis and
      surgery for initial treatment of acute limb ischaemia. DATA COLLECTION AND
      ANALYSIS: We independently assessed trial quality and extracted data. Agreement
      was reached by consensus. We performed analyses using odds ratios (ORs) and 95%
      confidence intervals (CIs). MAIN RESULTS: We identified no new studies for this
      update. We included five trials with a total of 1292 participants; agents used
      for thrombolysis were recombinant tissue plasminogen activator and urokinase.
      Trials were generally of moderate methodological quality. The quality of evidence
      according to GRADE was generally low owing to risk of bias (lack of blinding),
      imprecision in estimates, and heterogeneity.Trial results showed no clear
      differences in limb salvage, amputation, or death at 30 days (odds ratio (OR)
      1.02, 95% confidence interval (CI) 0.41 to 2.55, 4 studies, 636 participants; OR
      0.97, 95% CI 0.51 to 1.85, 3 studies, 616 participants; OR 0.59, 95% CI 0.31 to
      1.14, 4 studies, 636 participants, respectively), and we rated the evidence as
      low, low, and moderate quality, respectively. Trial results show no clear
      differences for any of the three outcomes at six months or one year between
      initial surgery and initial thrombolysis. A single study evaluated vessel
      patency, so no overall association could be determined (OR 0.46, 95% CI 0.08 to
      2.76, 20 participants; very low-quality evidence). Evidence of increased risk of
      major haemorrhage (OR 3.22, 95% CI 1.79 to 5.78, 4 studies, 1070 participants;
      low-quality evidence) and distal embolisation (OR 31.68, 95% CI 6.23 to 161.07, 3
      studies, 678 participants; very low-quality evidence) was associated with
      thrombolysis treatment at 30 days, and there was no clear difference in stroke
      (OR 5.33, 95% CI 0.95 to 30.11, 5 studies, 1180 participants; low-quality
      evidence). Participants treated by initial thrombolysis had a greater reduction
      in the level of intervention required, compared with a pre-intervention
      prediction, at 30 days (OR 9.06, 95% CI 4.95 to 16.56, 2 studies, 502
      participants). None of the included studies evaluated time to thrombolysis as an
      outcome. AUTHORS' CONCLUSIONS: There is currently no evidence in favour of either
      initial thrombolysis or initial surgery as the preferred option in terms of limb
      salvage, amputation, or death at 30 days, six months, or one year. Low-quality
      evidence suggests that thrombolysis may be associated with higher risk of
      haemorrhagic complications and ongoing limb ischaemia (distal embolisation). The
      higher risk of complications must be balanced against risks of surgery in each
      individual case. Trial results show no statistical difference in stroke, but the
      confidence interval is very wide, making it difficult to interpret whether this
      finding is clinically important. We used GRADE criteria to assess the quality of
      the evidence as generally low. We downgraded quality owing to risk of bias,
      imprecision, and heterogeneity between included studies.

PMID- 30095171
TI  - Overexpression of MCM10 promotes cell proliferation and predicts poor prognosis
      in prostate cancer.
AB  - BACKGROUND: Prostate cancer (PCa) is one of the most malignant tumors of the male
      urogenital system. There is an urgent need to identify novel biomarkers for PCa.
      METHODS: In this study, we evaluated the expression levels of MCM10 in prostate
      cancer by analyzing public datasets (including The Cancer Genome Atlas and
      GSE21032). Furthermore, loss of function assays was performed to evaluate the
      effects of MCM10 on cell proliferation, apoptosis, and colony formation.
      Furthermore, we performed microarray and bioinformatics analyses to explore the
      potential mechanisms of MCM10. RESULTS: In the present study, we for the first
      time revealed MCM10 was significantly upregulated in PCa. Moreover, we found
      increased MCM10 expression was significantly associated with advanced clinical
      stage and high Gleason score PCa. Kaplan-Meier analysis demonstrated higher MCM10
      expression was associated with a poorer patient prognosis in PCa. Furthermore,
      loss of function assays showed that MCM10 knockdown inhibited cell proliferation
      and colony formation, but promoted cell apoptosis. Additionally, we performed
      microarray and bioinformatics analysis and found MCM10 regulated PCa progression
      by regulating a series of biological processes including cancer, cell death, and
      apoptosis. CONCLUSIONS: These results suggest that MCM10 may be a potential
      diagnostic and therapeutic target for PCa.

PMID- 30095172
TI  - Intravesical prostatic protrusion is not always the same shape: Evaluation by
      preoperative cystoscopy and outcome in HoLEP.
AB  - AIMS: To examine how morphological differences in intravesical prostatic
      protrusion (IPP) predict outcome of Holmium laser enucleation of prostate (HoLEP)
      treatment. METHODS: We analyzed 173 patients who had undergone HoLEP in our
      hospital. The protrusion shape was evaluated by outpatient preoperative flexible
      cystoscopy and classified into five groups: A, no protrusion; B, middle lobe
      only; C, unilateral lobe only; D, bilateral lobes; and E, B + C or B + D. Paired
      match analysis that adjusted for preoperative International Prostate Symptom
      Score (IPSS) voiding/storage subscores and IPP was performed between the group
      with middle lobe protrusion (B + E) and the group without it (C + D). RESULTS:
      Type A prostate shape was found in 23 patients, type B in 14, type C in 31, type
      D in 71, and type E in 34. Groups with middle lobe protrusion (B and E) had
      better changes in the total IPSS (P < 0.05) and the IPSS storage subscore (P <
      0.01). Pair matching identified 37 patients each with or without middle lobe
      protrusion. The group with middle lobe protrusion had significantly more improved
      total IPSS (-17.5 +/- 7.5 vs -13.5 +/- 8.3, P < 0.05) and IPSS storage subscore (
      6.9 +/- 3.4 vs -4.8 +/- 3.3, P < 0.05) than did those without middle lobe
      protrusion. CONCLUSIONS: Patients with middle lobe protrusion had greater IPSS
      improvement after HoLEP than those having comparable-length IPP but without
      middle lobe protrusion. IPP is not always the same shape and should be clinically
      divided into at least two groups.

PMID- 30095173
TI  - Efficacy of adjunctive photodynamic therapy in the treatment of generalized
      aggressive periodontitis: A randomized controlled clinical trial.
AB  - OBJECTIVES: Generalized aggressive periodontitis (GAgP) is a distinct type of
      periodontal disease characterized by rapid loss of attachment and alveolar bone
      occurring in young individuals. Photodynamic therapy (PDT) was introduced in
      periodontology as an adjunctive approach to non-surgical periodontal treatment
      (NPT) in periodontitis patients. In this trial, the aim was to evaluate the
      clinical and microbiological effects of adjunctive PDT to NPT in patients with
      GAgP. METHODS: In this prospective controlled clinical study, 24 systemically
      healthy, non-smoking subjects with GAgP were enrolled. Subjects were randomly
      assigned into a control group (n = 12) treated with NPT only or to a test group
      (n = 12) treated with NPT and PDT. Plaque index, sulcus bleeding index (SBI),
      probing depth (PD), relative attachment level, gingival recession, and tooth
      mobility were recorded at baseline and on day 63. Microbiological samples were
      obtained from the sites with PD >= 5 mm at both time periods and evaluated for
      Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella
      intermedia, Tannerella forsythia, and Treponema denticola via micro-IDent(r)
      test. RESULTS: Clinical and microbial parameters declined significantly in both
      groups after the treatments (P < 0.01). The comparisons between the groups showed
      that only the full mouth SBI score of the test group was significantly lower than
      the control group on day 63 (P < 0.05). Although the reduction in
      periodontopathogens of the test group was greater than the control group, there
      was no significant difference between the groups (P > 0.05). CONCLUSIONS: Within
      the limits of this study, it can be concluded that in the treatment of GAgP,
      usage of PDT as an adjunct to NPT does not lead to any beneficial effects on the
      investigated clinical and microbiological parameters except for SBI.
      Nevertheless, the statistically significant difference for the SBI score
      demonstrates that PDT may have additional effect on the reduction in gingival
      bleeding. Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.

PMID- 30095174
TI  - N2pc reflects two modes for coding the number of visual targets.
AB  - Humans share with a variety of animal species the spontaneous ability to detect
      the numerical correspondence between limited quantities of visual objects and
      discrete auditory events. Here, we explored how such mental representation is
      generated in the visual modality by monitoring a parieto-occipital ERP component,
      N2pc, whose amplitude covaries with the number of visual targets in explicit
      enumeration. Participants listened to an auditory sequence of one to three tones
      followed by a visual search display containing one to three targets. In
      Experiment 1, participants were asked to respond based on the numerical
      correspondence between tones and visual targets. In Experiment 2, participants
      were asked to ignore the tones and detect a target presence in the search
      display. The results of Experiment 1 showed an N2pc amplitude increase determined
      by the number of visual targets followed by a centroparietal ERP component
      modulated by the numerical correspondence between tones and visual targets. The
      results of Experiment 2 did not show an N2pc amplitude increase as a function of
      the number of visual targets. However, the numerical correspondence between tones
      and visual targets influenced N2pc amplitude. By comparing a subset of
      amplitude/latency parameters between Experiment 1 and 2, the present results
      suggest N2pc reflects two modes for representing the number of visual targets.
      One mode, susceptible to subjective control, relies on visual target segregation
      for exact target individuation, whereas a different mode, likely enabling
      spontaneous cross-modal matching, relies on the extraction of rough information
      about number of targets from visual input.

PMID- 30095175
TI  - Production and recovery of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) from
      biodiesel liquid waste (BLW).
AB  - Polyhydroxyalkanoates (PHAs) has been paid great attention because of its useful
      thermoplastic properties and complete degradation in various natural
      environments. But, at industrial level, the successful commercialization of PHAs
      is limited by the high production cost due to the expensive carbon source and
      recovery processes. Pseudomonas mendocina PSU cultured for 72 h in mineral salts
      medium (MSM) containing 2% (v/v) biodiesel liquid waste (BLW) produced 79.7 wt%
      poly(3-hydroxybutyrate) (PHB) at 72 h. In addition, this strain produced 43.6 wt%
      poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with 8.6 HV mol% at 60 h when
      added with 0.3% sodium propionate. The synthesized intracellular PHA granules
      were recovered and purified by the recently reported biological method using
      mealworms. The weight average molecular weight (Mw ) and number average molecular
      weight (Mn ) of the biologically extracted PHA were higher than that from the
      chloroform extraction with comparable melting temperature (Tm ) and high purity.
      This study has successfully established a low-cost process to synthesize PHAs
      from BLW and subsequently confirmed the ability of mealworms to extract PHAs from
      various kinds of bacterial cells.

PMID- 30095176
TI  - Impact of Epstein-Barr virus serological status on clinical outcomes in adult
      patients with inflammatory bowel disease.
AB  - BACKGROUND: Little is known about the impact of Epstein-Barr virus (EBV)
      infection on clinical outcomes in adults with inflammatory bowel disease (IBD).
      AIM: To evaluate seroprevalence, seroconversion rate and complications associated
      with EBV infection in an adult IBD cohort attending a tertiary care hospital in
      Spain between 2006 and 2016. METHODS: EBV serological status was determined. In
      seronegative patients, the seroconversion rate was evaluated. The complications
      associated with primary and latent EBV infection are described. RESULTS: One
      thousand four hundred and eighty-three patients over the age of 17 were included
      in the study (mean age at EBV serological status determination was 48.3). Overall
      seroprevalence of EBV was 97.4% (95% CI: 96.6%-98.2%). The seroconversion rate
      was 29.7% (95% CI: 16.2-45.9) after a mean of 47.5 months. There were no
      differences in seroconversion rates between patients 35 years or younger and
      patients older than 35 years. A 66-year-old man, on treatment with thiopurines,
      developed lymphoma and a hemophagocytic syndrome during a primary EBV infection.
      Overall, six patients (one with primary infection and five with prior EBV
      infection) developed lymphoma. In three of five patients with lymphoma and
      thiopurine use, EBV was associated to the development of lymphoma. CONCLUSIONS:
      There is a small percentage of adults with IBD at risk of primary EBV infection.
      The risks of seroconversion and its complications remain through adulthood. Our
      results suggest that, when considering the use of thiopurines in IBD, the
      information on EBV serological status should be taken into account at any age.

PMID- 30095177
TI  - Subclinical cardiovascular damage in patients with HCV cirrhosis before and after
      treatment with direct antiviral agents: a prospective study.
AB  - BACKGROUND: Cirrhosis is associated with morpho-functional cardiovascular
      alterations. AIMS: To detect early features of cardiovascular damage in HCV
      compensated cirrhotic patients using myocardial deformation indices and carotid
      arterial stiffness, and, further, to evaluate their short-term behaviour after
      HCV eradication with direct antiviral agents (DAAs). METHODS: Thirty-nine
      consecutive patients with HCV cirrhosis, without previous cardiovascular events,
      were studied and matched for age, gender and cardiovascular risk factors to 39
      controls without liver or cardiovascular disease. Patients and controls underwent
      a baseline echocardiographic evaluation including global longitudinal strain and
      ultrasound scan of carotid arteries. HCV-cirrhotics were reassessed by
      echocardiography and carotid ultrasound after obtaining sustained virological
      response (SVR) on DAAs. RESULTS: HCV-cirrhotics showed at baseline a
      significantly reduced global longitudinal strain compared to controls -18.1 (16.3
      20.5) vs -21.2 (20.4-22.3), P < 0.001. They also had a significantly higher pulse
      wave velocity 8.6 (7.7-9.1) m/s vs 6.6 (6.0-7.1) m/s, P = 0.0001, and beta
      stiffness index 12.4 (11.1-13.5) vs 8.6 (8.0-9.2) P = 0.0001. At multiple
      regression analysis, diabetes and HCV cirrhosis were independent predictors of
      global longitudinal strain. All HCV-cirrhotic patients had SVR on DAAs. Follow-up
      available in 32 of 39 (82%) at 9 (8-10) months showed a significant improvement
      of tricuspid annular plane systolic excursion (P = 0.01) and lateral E' velocity
      compared to baseline (P = 0.001). CONCLUSIONS: HCV-cirrhotics show a significant
      rate of subclinical cardiac and vascular abnormalities. At a time when their
      survival is less linked to progression of liver disease, due to viral eradication
      on DAAs, cardiovascular morbidity and mortality may take a significant role.

PMID- 30095178
TI  - Epistemic layers in development planning: A case study of the health sector in
      the Gunungkidul District, Indonesia.
AB  - The paper analyses how knowledge systems and epistemic cultures contribute to
      development planning through conduct of a microqualitative sociological case
      study of the health sector in Indonesia. The data were attained from 37 in-depth
      interviews and a stakeholder engagement workshop conducted in Gunungkidul,
      Yogyakarta, complemented with documentary media analysis. Our findings show that
      centralisation continues to exist in the development planning practice within the
      decentralisation era. This is shown through dependence on budget prescriptions
      and indicators from the centre in Jakarta. Further, this study demonstrates how
      the integration of indicators in the development planning process is hampered by
      myopic practices of government officials at the district level where there is
      evidence of an absence of verified knowledge in the Health Bureau of the District
      of Gunungkidul. Furthermore, there is dependence on data and information from
      volunteers in the Health Integrated Service Post (Posyandu) at the local village
      level. This study reveals, therefore, that development planning operates at three
      levels, yet with different knowledge systems and epistemic cultures at each
      level: central, district, and village.

PMID- 30095180
TI  - Study of the factors causing medical disputes in a Third-Level Grade A Hospital
      in Shanghai.
AB  - OBJECTIVE: By analyzing cases of medical disputes occurred in one of top
      hospitals in Shanghai from 2012 to 2014, the paper tries to determine the causes
      and cures of the disputes based on relevant national and international
      experience. METHODS: A cluster sample of medical disputes occurred in the
      hospital from 2012 to 2014 was selected, to which logistic regression analysis
      was applied in order to determine the factors causing medical disputes. RESULTS:
      Inadequate experience in dealing with unexpected incidents (P = 0.002), violation
      of routine procedures for diagnosis and treatment (P = 0.004), and therapeutic
      effects (P = 0.007) were found to be statistically significant. CONCLUSION:
      Medical disputes in the hospital would be substantially reduced by taking such
      measures as strengthening trainings on how to deal with unexpected incidents for
      medical staff, standardizing procedures for clinical practices, and improving the
      therapeutic effects of various diseases.

PMID- 30095179
TI  - All-Silicon Broadband Ultraviolet Metasurfaces.
AB  - Featuring high photon energy and short wavelength, ultraviolet (UV) light enables
      numerous applications such as high-resolution imaging, photolithography, and
      sensing. In order to manipulate UV light, bulky optics are usually required, and
      hence do not meet the fast-growing requirements of integration in compact
      systems. Recently, metasurfaces have shown unprecedented control of light,
      enabling substantial miniaturization of photonic devices from terahertz to
      visible regions. However, material challenges have hampered the realization of
      such functionalities at shorter wavelengths. Herein, it is experimentally
      demonstrated that all-silicon (Si) metasurfaces with thicknesses of only one
      tenth of the working wavelength can be designed and fabricated to manipulate
      broadband UV light with efficiencies comparable to plasmonic metasurface
      performance in infrared (IR). Also, for the first time, photolithography enabled
      by metasurface-generated UV holograms is shown. Such performance enhancement is
      attributed to increased scattering cross sections of Si antennas in the UV range,
      which is adequately modeled via a circuit. The new platform introduced here will
      deepen the understanding of light-matter interactions and introduce even more
      material options to broadband metaphotonic applications, including those in
      integrated photonics and holographic lithography technologies.

PMID- 30095181
TI  - Lanthanide Coordination Polymers and MOFs based on the Dicyanodihydridoborate
      Anion.
AB  - New lanthanide cyanoborates were synthesized from anhydrous lanthanide chlorides
      and the acid H[BH2 (CN)2 ] in either acetonitrile or pyridine. Reactions in
      acetonitrile lead to three-dimensional, anionic metal-organic frameworks (MOFs) 3
      infinity [Ln2 {BH2 (CN)2 }9 ]?[Ln(CH3 CN)9 ] (Ln=Ce, Eu, Tb) which incorporate
      complex cations [Ln(CH3 CN)9 ]3+ in the pores of the framework for charge
      compensation. In contrast, the reactions in pyridine result in the formation of
      one-dimensional coordination polymers 1 infinity [H(py)2 ][LnCl2 {BH2 (CN)2 }2
      (py)2 ]?0.5 py (Ln=Ce, Pr, py=pyridine) with [H(py)2 ]+ as counter ions for the
      anionic strand structure. The products show intense photoluminescence, for Ce3+
      based on 5d-4f transitions in the blue spectral region, whereas the Eu3+ and Tb3+
      compounds exhibit characteristic photoluminescence based on 4f-4f transitions of
      the respective lanthanide ions. The observed photoluminescence is mainly
      attributed to a direct excitation of the lanthanide ions and sensitization of the
      lanthanide ions by the [BH2 (CN)2 ]- anions. These results mark the utilized
      borate anions as versatile building block for new coordination compounds.

PMID- 30095182
TI  - Solution-Based Processing of Optoelectronically Active Indium Selenide.
AB  - Layered indium selenide (InSe) presents unique properties for high-performance
      electronic and optoelectronic device applications. However, efforts to process
      InSe using traditional liquid phase exfoliation methods based on surfactant
      assisted aqueous dispersions or organic solvents with high boiling points
      compromise electronic properties due to residual surface contamination and
      chemical degradation. Here, these limitations are overcome by utilizing a
      surfactant-free, low boiling point, deoxygenated cosolvent system. The resulting
      InSe flakes and thin films possess minimal processing residues and are
      structurally and chemically pristine. When employed in photodetectors, individual
      InSe nanosheets exhibit a maximum photoresponsivity of ~5 * 107 A W-1 , which is
      the highest value of any solution-processed monolithic semiconductor to date.
      Furthermore, the surfactant-free cosolvent system not only stabilizes InSe
      dispersions but is also amenable to the assembly of electronically percolating
      InSe flake arrays without posttreatment, which enables the realization of
      ultrahigh performance thin-film photodetectors. This surfactant-free,
      deoxygenated cosolvent approach can be generalized to other layered materials,
      thereby presenting additional opportunities for solution-processed thin-film
      electronic and optoelectronic technologies.

PMID- 30095183
TI  - Effect of TRPV4 activation in a rat model of detrusor underactivity induced by
      bilateral pelvic nerve crush injury.
AB  - AIMS: To produce an animal model of peripheral neurogenic detrusor underactivity
      (DU) and to evaluate the effect of TRPV4 receptor activation in this DU model.
      METHODS: In female Sprague-Dawley rats, bilateral pelvic nerve crush (PNC) was
      performed by using sharp forceps. After 10 days, awake cystometrograms (CMG) were
      recorded in sham and PNC rats. A TRPV4 agonist (GSK 1016790A) with or without a
      TRPV4 antagonist (RN1734) were administered intravesically and CMG parameters
      were compared before and after drug administration in each group. The TRPV4
      transcript level in the bladder mucosa and histological changes were also
      evaluated. RESULTS: In CMG, PNC rats showed significant increases in
      intercontraction intervals (ICI), number of non-voiding contractions (NVCs),
      baseline pressure, threshold pressure, bladder capacity, voided volumes, and post
      void residual (PVR) compared to sham rats. Contraction amplitude and voiding
      efficiency were significantly decreased in PNC rats. In PNC rats, intravesical
      application of GSK1016790A (1.5 MUM) significantly decreased ICI, bladder
      capacity, voided volume, and PVR without increasing NVCs, and these effects were
      blocked by RN1734 (5.0 MUM). In contrast, 1.5 MUM GSK1016790A had no significant
      effects on CMG parameters in normal rats. TRPV4 expression within the bladder
      mucosa of PNC rats was increased in association with urothelial thickening.
      CONCLUSIONS: Rats with bilateral PNC showed characteristics of DU, and this model
      seems appropriate for further evaluation of peripheral neurogenic mechanisms of
      DU. Also, TRPV4 receptors, the activation of which reduced bladder capacity and
      PVR, could be a target for DU treatment.

PMID- 30095184
TI  - An exploratory case study of the organizational functioning of a decision-making
      and referral support call center for frontline providers of maternal and new born
      care in the Greater Accra Region of Ghana.
AB  - A call center was designed and started implementation in the Greater Accra Region
      of Ghana in 2015, to support frontline provider decision-making and referral for
      maternal and new born care. This study aimed to understand the organizational
      functioning of the center and lessons for design improvement, implementation, and
      scale-up. The study design was a single case study. Data collection involved
      participant and nonparticipant observation, conversations, and in-depth
      interviews with call center staff. Data were coded and analyzed manually.
      Findings showed a high adherence to call center protocols, good client service
      skills, a strong local sense of ownership of the center, and staff resilience in
      performing their functions despite a context of scarce resources and no prior
      experience with running a call center. Perceptions of lack of involvement of some
      call center staff in decision-making, and the resource constrained working
      conditions sometimes hampered the functioning of the center. The locally driven
      bottom-up process used to establish the center appeared to be an important
      element in sustaining it despite the resource constraints. More attention to
      locally driven bottom-up approaches, organizational functioning, and resilience
      are critical to develop and sustain innovations for health outcome improvement in
      resource-constrained contexts.

PMID- 30095185
TI  - Bioconjugation with Maleimides: A Useful Tool for Chemical Biology.
AB  - Maleimide chemistry stands out in the bioconjugation toolbox by virtue of its
      synthetic accessibility, excellent reactivity, and practicability. The second
      generation of clinically approved antibody-drug conjugates (ADC) and much of the
      current ADC pipeline in clinical trials contain the maleimide linkage. However,
      thiosuccinimide linkages are now known to be less robust than once thought, and
      ergo, are correlated with suboptimal pharmacodynamics, pharmacokinetics, and
      safety profiles in some ADC constructs. Rational design of novel generations of
      maleimides and maleimide-type reagents have been reported to address the
      shortcomings of classical maleimides, allowing for the formation of robust
      bioconjugate linkages. This review highlights the main strategies for rational
      reagent design that have allowed irreversible bioconjugations in cysteines,
      reversible labelling strategies and disulfide re-bridging.

PMID- 30095187
TI  - Single-Site Heterogeneous Catalysts: From Synthesis to NMR Signal Enhancement.
AB  - Catalysts with well-defined, single, active centers are of great importance and
      their utilization allows the gap between homo- and heterogeneous catalysis to be
      bridged and, importantly, the main selectivity problem of heterogeneous catalysis
      and the main separation challenge of homogeneous catalysis to be overcome.
      Moreover, the use of single-site catalysts allows the NMR signal to be
      significantly enhanced through the pairwise addition of two hydrogen atoms from a
      parahydrogen molecule to an unsaturated substrate. This review covers the
      fundamentals of the synthesis of single-site catalysts and shows the new aspects
      of their applications in both modern catalysis and the field of parahydrogen
      based hyperpolarization. The different novel aspects of the formation and
      utilization of single-site catalysts, along with the possibility of NMR signal
      enhancement observations are described.

PMID- 30095186
TI  - Global metabolomic responses in urine from atm deficient mice in response to
      LD50/30 gamma irradiation doses.
AB  - Exposures to ionizing radiation (IR) may either be accidental or intentional, for
      medical purposes or even through terrorist actions. As certain populations emerge
      to be more radiosensitive than others, it is imperative to assess those
      individuals and treat them accordingly. To demonstrate the feasibility of rapid
      identification of such cases, we utilized the highly radiosensitive mouse model
      Atm-/- in the C57BL/6 background, and evaluated the urinary responses in 8-10
      week old male mice at early time points (4, 24, and 72 h) after exposure to their
      respective LD50/30 doses [4 Gy for Atm-/- , and 8 Gy for wild type (WT)]. Urinary
      profiles from heterozygous animals exhibited remarkably similar responses to WT
      before and after radiation exposure. However, genotypic differences (WT or Atm-/-
      ) were the primary driver to responses to radiation. Putative metabolites were
      validated through tandem mass spectrometry and included riboflavin, uric acid, d
      ribose, d-glucose, pantothenic acid, taurine, kynurenic acid, xanthurenic acid, 2
      oxoadipic acid, glutaric acid, 5'-deoxy-5'-methylthioadenosine, and hippuric
      acid. These metabolites mapped to several interconnected metabolic pathways which
      suggest that radiosensitive mouse models have underlying differences
      significantly impacting overall metabolism. This was further amplified by
      ionizing radiation at different time points. This study further emphasizes that
      genetically based radiosensitivity is reflected in the metabolic processes, and
      can be directly observed in urine. These differences in turn can potentially be
      used to identify individuals that may require altered medical treatment in an
      emergency radiological situation or modification of a regimen during a
      radiotherapy session. Environ. Mol. Mutagen. 59:576-585, 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30095188
TI  - X-ray Constrained Spin-Coupled Wavefunction: a New Tool to Extract Chemical
      Information from X-ray Diffraction Data.
AB  - The X-ray constrained wavefunction (XCW) approach is a reliable and widely used
      method of quantum crystallography that allows the determination of wavefunctions
      compatible with X-ray diffraction data. So far, all the existing XCW techniques
      have been developed in the framework of molecular orbital theory and,
      consequently, provide only pictures of the "experimental" electronic structures
      that are far from the traditional chemical perception. Here a new strategy is
      proposed that, by combining the XCW philosophy with the spin-coupled method of
      valence bond theory, enables direct extraction of traditional chemical
      information (e.g., weights of resonance structures) from X-ray diffraction
      measurements. Preliminary results have shown that the new technique is really
      able to efficiently capture the effects of the crystal environment on the
      electronic structure, and can be considered as a new useful tool to perform
      chemically sound analyses of the X-ray diffraction data.

PMID- 30095189
TI  - Direct Synthesis of Heavy Grignard Reagents: Challenges, Limitations, and
      Derivatization.
AB  - The direct synthesis of organocalcium compounds (heavy Grignard reagents) by the
      reduction of organyl halides with activated calcium powder succeeded in a
      straightforward manner for organic bromides and iodides that are bound at sp2 
      hybridized carbon atoms. Extension of this strategy to alkyl halides was very
      limited, and only the reduction of trialkylsilylmethyl bromides and iodides with
      activated calcium allowed the isolation of the corresponding heavy Grignard
      reagents. Substitution of only one hydrogen atom of the methylene moiety by a
      phenyl or methyl group directed this reduction toward the Wurtz-type coupling and
      the formation of calcium halide and the corresponding C-C coupling product. The
      stability of the methylcalcium and benzylcalcium derivatives in ethereal solvents
      suggests an unexpected reaction behavior of the intermediate organyl halide
      radical anions. Quantum chemical calculations verify a dependency between the
      ease of preparative access to organocalcium complexes and the C-I bond lengths of
      the organyl iodides. The bulkiness of the trialkylsilyl group is of minor
      importance. Chloromethyltrimethylsilane did not react with activated calcium;
      however, halogen-exchange reactions allowed the isolation of [Ca(CH2 SiMe3
      )(thf)3 (MU-Cl)]2 . Furthermore, the metathetical approach of reacting [Ca(CH2
      SiMe3 )I(thf)4 ] with KN(SiMe3 )2 and the addition of N,N,N',N'',N''
      pentamethyldiethylenetriamine (pmdeta) allowed the isolation of heteroleptic
      [CaCH2 SiMe3 {N(SiMe3 )2 }(pmdeta)]. In the reaction of this derivative with
      phenylsilane, the trimethylsilylmethyl group proved to be more reactive than the
      bis(trimethylsilyl)amido substituent.

PMID- 30095190
TI  - Borabicyclo[3.2.0]heptadiene: A Fused Bicyclic Isomer of Borepin.
AB  - A new isomer of borepin, identified as 2-borabicyclo[3.2.0]hepta-3,6-diene by
      single-crystal X-ray diffraction and heteronuclear NMR spectroscopy, was obtained
      by reaction of 1-mesityl-2,3,4,5-tetraphenylborole with the diaminoalkyne
      bis(piperidyl)acetylene. Analogous reactions of the alkyne with other borole
      derivatives generated seven-membered borepins, in which a second equivalent of
      the alkyne was found to insert into the exocyclic B-C bond. Results of
      mechanistic DFT studies as well as differences in the reactivity of the boroles
      toward the diaminoalkyne are discussed.

PMID- 30095191
TI  - Yellow Emission from Low Coordination Site of Sr2 SiO4 :Eu2+ , Ce3+ : Influence
      of Lanthanide Dopants on the Electron Density and Crystallinity in Crystal Site
      Engineering Approach.
AB  - Lanthanide doping through a crystal site engineering approach tunes the emission
      wavelength suitable for LED applications, but weak emission from low coordination
      sites remains a huge challenge. Herein the use of a sensitizer is reported to
      enhance the emission strength and unravel the crystallinity and phase, as this
      approach demands a large amount of dopants. Doping of Eu2+ ions at SrO10 and SrO9
      sites of Sr2 SiO4 (S2 S), respectively, tunes the emission from green to yellow
      and controlled doping of a Ce3+ sensitizer quadruples the quantum efficiency of
      yellow emission. Remarkably, doping of Eu2+ at the SrO9 site produces
      polycrystals, whereas co-doping of Ce3+ and Eu2+ at the same site produces single
      crystals. DFT calculations further delineate the underlying changes wherein
      strong interaction of dopant with its neighbours determines the electron density,
      and thus the crystallinity and phase, rather than usual explanation of aliovalent
      conditions, which is further substantiated by TEM results. Irrespective of dopant
      valence, use of large amounts of dopants and their interaction with the host is
      responsible for the crystallinity and phase change (alpha'-S2 S to beta-S2 S).
      The XPS valence band spectra experimentally evidences the changes in bonding
      nature of O 2p and O 2s orbitals of silicate and its electron density, due to
      doping at the two sites. In short, the outcomes resulting from this work could be
      extended for the development of other two-coordination site lanthanide-doped
      materials and crystallization of inorganic materials.

PMID- 30095192
TI  - Polyoxometalate-Decorated g-C3 N4 -Wrapping Snowflake-Like CdS Nanocrystal for
      Enhanced Photocatalytic Hydrogen Evolution.
AB  - Photocatalytic hydrogen evolution technology is recognized as a promising
      approach to relieving the growing energy crisis. Therefore, the development of a
      stable high-performance photocatalyst has long been the focus of research. In
      this work, quaternary composite materials involving a snowflake-like CdS
      nanocrystal wrapped by different amounts of polyoxometalate-decorated g-C3 N4 and
      polypyrrole (GPP@CdS) have been synthesized as photocatalysts for hydrogen
      production under visible-light irradiation. It has been revealed that the best
      composite (40 % GPP@CdS composite) exhibits hydrogen production activity of 1321
      MUmol, which exceeds that of CdS by a factor of more than two, and can be used in
      at least seven cycles with negligible loss of activity. The enhanced
      photocatalytic performance has been primarily attributed to the efficient synergy
      of CdS, g-C3 N4 , polypyrrole (PPy), and the polyoxometalate Ni4 (PW9 )2 . It
      should be noted that the introduction of PPy and g-C3 N4 into the title composite
      simultaneously promotes electron/hole pair separation and photocatalytic
      stability, whereas Ni4 (PW9 )2 serves as an efficient electron modulator and
      extra catalytic active site.

PMID- 30095193
TI  - Mapping the Magnetic Anisotropy at the Atomic Scale in Dysprosium Single-Molecule
      Magnets.
AB  - The anisotropy of the magnetic properties of molecular magnets is a key
      descriptor in the search for improved magnets. Herein, it is shown how an
      analytical approach using single-crystal polarized neutron diffraction (PND)
      provides direct access to atomic magnetic susceptibility tensors. The technique
      was applied for the first time to two Dy-based single-molecule magnets and showed
      clear axial atomic susceptibility for both DyIII ions. For the triclinic system,
      bulk magnetization methods are not symmetry-restricted, and the experimental
      magnetic easy axes from both PND, angular-resolved magnetometry (ARM), and
      theoretical approaches all match reasonably well. ARM curves simulated from the
      molecular susceptibility tensor determined with PND show strong resemblance with
      the experimental ones. For the monoclinic compound, comparison can only be made
      with the theoretically calculated magnetic anisotropy, and in this case PND
      yields an easy-axis direction that matches that predicted by electrostatic
      methods. Importantly, this technique allows the determination of all elements of
      the magnetic susceptibility tensor and not just the easy-axis direction, as is
      available from electrostatic predictions. Furthermore, it has the capacity to
      provide each of the anisotropic magnetic susceptibility tensors for all
      independent magnetic ions in a molecule and thus allows studies on polynuclear
      complexes and compounds of higher crystalline symmetry than triclinic.

PMID- 30095194
TI  - Possible role of hydrogen sulfide as an endogenous relaxation factor in the rat
      bladder and prostate.
AB  - AIMS: To clarify the roles of hydrogen sulfide (H2 S), an endogenous
      gasotransmitter, in the rat bladder and prostate, we investigated the
      distribution of enzymes related to H2 S biosynthesis (cystathionine beta-synthase
      [CBS], cystathionine gamma-lyase [CSE], 3-mercaptopyruvate sulfurtransferase
      [MPST], cysteine aminotransferase [CAT], and D-amino acid oxidase [DAO]) and the
      content of H2 S. We also investigated the effects of H2 S donors (NaHS and
      GYY4137) on the contractility of both tissues and on micturition. METHODS: The
      distribution of these enzymes was investigated by real-time PCR, Western blot,
      and immunohistochemistry. Tissue H2 S content was measured by the methylene blue
      method. The effects of NaHS (1 * 10-9 to 3 * 10-4  M) were evaluated on carbachol
      (10-5  M)-induced pre-contracted bladder strips, and on noradrenaline (10-5  M)
      induced pre-contracted prostate strips, which were pretreated with propranolol
      (10-6  M). In addition, in urethane-anesthetized male Wistar rats, the effects of
      intravesically instilled GYY4137 (10-8 , 10-7 , and 10-6  M) on micturition were
      evaluated by cystometry. RESULTS: MPST and CAT were detected in the bladder and
      prostate, CBS was only detected in the prostate, while CSE and DAO were not
      detected in both tissues. Immunoreactivity of these enzymes was mainly detected
      in the urothelium and smooth muscle layer of the bladder and in the prostate
      glandular epithelium. H2 S was detected in both tissues. NaHS dose-dependently
      induced relaxation of pre-contracted bladder and prostate strips. Intravesically
      instilled GYY4137 significantly prolonged intercontraction intervals.
      CONCLUSIONS: It is possible that H2 S can function as an endogenous relaxation
      factor in the rat bladder and prostate.

PMID- 30095195
TI  - Effect of culture duration on chondrogenic preconditioning of equine bone marrow
      mesenchymal stem cells in self-assembling peptide hydrogel.
AB  - Ex vivo induction of chondrogenesis is a promising approach to improve upon the
      use of bone marrow mesenchymal stem cells (MSCs) for cartilage tissue
      engineering. This study evaluated the potential to induce chondrogenesis with
      days of culture in chondrogenic medium for MSCs encapsulated in self-assembling
      peptide hydrogel. To simulate the transition from preconditioning culture to
      implantation, MSCs were isolated from self-assembling peptide hydrogel into an
      individual cell suspension. Commitment to chondrogenesis was evaluated by seeding
      preconditioned MSCs into agarose and culturing in the absence of the chondrogenic
      cytokine transforming growth factor beta (TGFbeta). Positive controls consisted
      of undifferentiated MSCs seeded into agarose and cultured in medium containing
      TGFbeta. Three days of preconditioning was sufficient to produce chondrogenic
      MSCs that accumulated ~75% more cartilaginous extracellular matrix than positive
      controls by day 17. However, gene expression of type X collagen was ~65-fold
      higher than positive controls, which was attributed to the absence of TGFbeta.
      Potential induction of immunogenicity with preconditioning culture was indicated
      by expression of major histocompatibility complex class II (MHCII), which was
      nearly absence in undifferentiated MSCs, and ~7% positive for preconditioned
      cells. These data demonstrate the potential to generate chondrogenic MSCs with
      days of self-assembling peptide hydrogel, and the ability to readily recover an
      individual cell suspension that is suited for injectable therapies. However,
      continued exposure to TGFbeta may be necessary to prevent hypertrophy indicated
      by type X collagen expression, while immunogenicity may be a concern for
      allogeneic applications. (c) 2018 Orthopaedic Research Society. Published by
      Wiley Periodicals, Inc. J Orthop Res.

PMID- 30095196
TI  - Impact of the route of clean intermittent catheterization on quality of life in
      children with lower urinary tract dysfunction.
AB  - AIMS: To compare the impact of the different routes for clean intermittent
      catheterization on the quality of life of children with lower urinary tract
      dysfunction. METHODS: In this cross-sectional study, all children and adolescents
      under treatment in our clinic from August 2011 to May 2012 who were on CIC for
      bladder dysfunction were included. To evaluate the technical difficulty and the
      discomfort associated with the procedure we used a standard visual analog scale.
      Quality of life was measured using the Pediatric Quality of Life Inventory
      Version 4.0. RESULTS: A total of 70 children including 38 (54.3%) boys and 32
      (45.7%) girls with a mean age of 11.8 +/- 3.6 years (range 5 to 18 years) were
      evaluated. The mean daily number of catheterizations was 4.2 +/- 1.1. CIC was
      performed through the urethra in 51 (72.9%) subjects and a stoma in 19 (27.1%). A
      45 (64.3%) were assisted by a caregiver to perform a catheterization. No
      differences in both difficulty and discomfort for performing CIC were observed
      between groups. Children who performed CIC through a stoma had a better quality
      of life scores for the physical (P = 0.015) and social functioning domains (P =
      0.011). CONCLUSION: The quality of life of children and adolescents performing
      CIC appears to be affected by the route of catheterization, with a worse
      performance for those using urethral catheterization.

PMID- 30095197
TI  - The role of the long non-coding RNA HOXA11-AS in promoting proliferation and
      metastasis of malignant tumors.
AB  - Long non-coding RNA (lncRNA) is one of the focuses and hotspots of biological
      research in recent years. At the same time, tumors have become the main disease
      that endangers human health. In recent years, a large number of researchers have
      explored the relationship between lncRNA and tumors. HOXA11-AS is one of these
      lncRNAs. The long non-coding RNA HOXA11 antisense RNA (HOXA11-AS) is a novel
      lncRNA recently discovered. It is found in a variety of tumors such as ovarian
      cancer, glioma, and gastric cancer (GC) and so on, and is defined as an oncogene.
      It promotes tumor proliferation and metastasis by interacting with proteins such
      as miRNA and EZH2. In this paper, we review the mechanism of interaction between
      HOXA11-AS and various tumors in recent years, and believe that it can be a
      potential tumor marker and therapeutic target in the future prevention and
      treatment of tumors.

PMID- 30095198
TI  - Structural and functional characterization of hMEX-3C Ring finger domain as an E3
      ubiquitin ligase.
AB  - MEX-3C, a novel RNA binding E3 ubiquitin ligases, contains two N-terminal
      heterogeneous nuclear ribonucleoprotein K homology (KH) domains and C-terminal
      Ring finger domain. Recent evidence has suggested that human MEX-3C has a strong
      bondage with carcinogenesis and the MEX-3C-mediated ubiquitination of RIG-I is
      essential for the antiviral innate immune response. Moreover, the Ring finger
      domain of MEX-3C could regulate the degradation of HLA-A2 (an MHC-I allotype)
      mRNA with a novel mechanism. However, the structural basis for the ubiquitination
      catalyzed by hMEX-3C Ring finger domain remains evasive. In this study, we solved
      the crystal structure of dimeric Ring finger domain of hMEX-3C and compared it
      with the complex structure of MDM2/MDMX-UbcH5b-Ub. Our ubiquitination assay
      demonstrated that the Ring finger domain of hMEX-3C acts as a ubiquitin E3 ligase
      in vitro, cooperating with specific E2 to mediate ubiquitination. Then, we
      identified several key residues in Ring finger domain of hMEX-3C possibly
      involved in the interaction with E2-Ub conjugate and analyzed the E3 ligase
      activities of wild type and mutants at key sites. Additionally, zinc chelation
      experiments indicated that the intact structural stability is essential for the
      self-ubiquitination activity of the Ring finger domain of hMEX-3C. Taken
      together, our studies provided new insight into the mechanism of the Ring finger
      domain of hMEX-3C that may play an important role in eliciting antiviral immune
      responses and therapeutic interventions.

PMID- 30095199
TI  - Thiazide but not loop diuretics is associated with hypomagnesaemia in the general
      population.
AB  - PURPOSE: Hypomagnesaemia has been associated with various adverse outcomes. Loop
      and thiazide diuretics promote urinary magnesium excretion. However, it is
      unknown if this links to hypomagnesaemia. We study if loop or thiazide diuretic
      use affects serum magnesium levels and if it associates with hypomagnesaemia. In
      addition, we study the effect of combining a potassium-sparing diuretic with a
      thiazide diuretic on the presence of hypomagnesaemia. METHODS: The study
      performed a cross-sectional analysis within 9820 participants from the
      prospective Rotterdam Study. Hypomagnesaemia was defined as a serum magnesium
      level <=0.72 mmol/L. Participants were categorized by defined daily dose (DDD),
      and all analyses were adjusted for age, sex, BMI, eGFR, serum potassium levels,
      proton pump inhibitor use, and comorbidities. RESULTS: Loop diuretic use was
      associated with higher serum magnesium levels (<1 DDD: 0.004 mmol/L 95% CI: 
      0.008; 0.017; 1 DDD: 0.023 mmol/L 95% CI: 0.013; 0.032; >1 DDD: 0.043 mmol/L 95%
      CI: 0.028; 0.057). Thiazide diuretic use was associated with lower serum
      magnesium levels (<1 DDD: -0.013 mmol/L 95% CI: -0.023; -0.002; >=1 DDD: -0.018
      mmol/L 95% CI: -0.028; -0.010), resulting in an increased odds ratio of
      hypomagnesaemia of 3.14 (95% CI: 1.67; 5.92) and 2.74 (95% CI: 1.57; 4.77),
      respectively. These effects were predominantly seen in participants using
      diuretics for more than 390 days. Combining thiazide diuretics with a potassium
      sparing agent was not associated with lower serum magnesium levels or
      hypomagnesaemia. CONCLUSIONS: Thiazide diuretic use is associated with lower
      serum magnesium levels and an increased risk of hypomagnesaemia. This increased
      risk is not seen in participants using a combination of thiazide diuretics with a
      potassium-sparing agent. The use of loop diuretics is not associated with an
      increased risk of hypomagnesaemia.

PMID- 30095200
TI  - Characterization of the two conformations adopted by the T3SS inner-membrane
      protein PrgK.
AB  - The pathogenic bacterium Salmonella enterica serovar Typhimurium utilizes two
      type III secretion systems (T3SS) to inject effector proteins into target cells
      upon infection. The T3SS secretion apparatus (the injectisome) is a large
      macromolecular assembly composed of over twenty proteins, many in highly
      oligomeric states. A sub-structure of the injectisome, termed the basal body,
      spans both membranes and the periplasmic space of the bacterium. It is primarily
      composed of three integral membranes proteins, InvG, PrgH, and PrgK, that form
      ring structures through which components are secreted. In particular, PrgK
      possesses a periplasmic region consisting of two globular domains joined by a
      linker polypeptide. We showed previously that in isolation, this region adopts
      two distinct conformations, of with only one is observed in the assembled basal
      body complex. Here, using NMR spectroscopy, we further characterize these two
      conformations. In particular, we demonstrate that the interaction of the linker
      region with the first globular domain, as found in the intact basal body, is
      dependent upon the cis conformation of the Leu77-Pro78 peptide. Furthermore, this
      interaction is pH-dependent due to coupling with hydrogen bond formation between
      Tyr75 and His42 in its neutral Ndelta1 H tautomeric form. This pH-dependent
      interaction may play a role in the regulation of the secretion apparatus
      disassembly in the context of bacterial infection.

PMID- 30095203
TI  - The relationship between moral injury appraisals, trauma exposure, and mental
      health in refugees.
AB  - BACKGROUND: Refugees are often exposed to multiple traumatic experiences, leading
      to elevated rates of psychological disorders. There is emerging evidence that
      appraisals of traumatic events as violating deeply held moral beliefs and
      frameworks (i.e., moral injury) impact negatively on refugee mental health.
      Despite this, no research has systematically investigated moral injury appraisals
      in refugees. METHOD: Participants were 222 refugees from diverse backgrounds who
      had recently resettled in Australia. They completed measures of mental health in
      Arabic, Farsi, Tamil, or English through an online survey. This study first
      investigated the factor structure of the Moral Injury Appraisals Scale (MIAS),
      and then examined the relationship between the moral injury factors and key
      predictor (age, gender, trauma exposure) and outcome (Posttraumatic stress
      disorder [PTSD] symptom clusters, anger, and depression) variables. RESULTS:
      Confirmatory factor analyses of the MIAS supported a two-factor model, comprising
      a Moral Injury-Other (MI-Other) factor (i.e., interpreting the violation as being
      enacted by others) and a Moral Injury-Self (MI-Self) factor (i.e., interpreting
      the violation as being enacted by oneself). Structural equation modeling analyses
      indicated that both factors were predicted by higher trauma exposure, and both
      predicted more severe anger and depression. Notably, while MI-Other was
      associated with more severe PTSD, MI-Self was associated with lower levels of
      intrusions. CONCLUSION: These results suggest that there may be subtypes of moral
      injury appraisals that are associated with different mental health outcomes.
      These findings have potential implications for designing treatments that address
      the psychological impact of the refugee experience.

PMID- 30095201
TI  - Surgical oncology at a major referral center in Ghana: Burden, staging, and
      outcomes.
AB  - BACKGROUND AND OBJECTIVES: Outcome data after surgery for cancer in Sub-Saharan
      Africa are insufficient. We aimed to describe the presentation and outcomes of
      patients with solid cancers managed at a tertiary hospital in Ghana. METHODS:
      Records of cancer patients admitted to Komfo Anokye Teaching Hospital general
      surgery wards from 2013 to 2016 were reviewed for data on presentation, staging,
      management, and mortality. Patients discharged alive were followed-up by biannual
      telephone calls to establish their postdischarge status. Survival analysis was
      performed for patients with pathologic or radiologic confirmation of cancer and
      adequate staging. RESULTS: A total of 343 patients were included. Of these, 76%
      were female. The most common diagnoses were breast 136 (40%), foregut 70 (20%),
      and colorectal 63 (18%) cancers. Cancer diagnosis was confirmed by pathology or
      radiology in 281 (82%) patients, but only 112 (40%) had adequate staging. Seventy
      four (66%) patients were stage IV. Two-year overall survival for all 343 patients
      was 22% to 69%, depending on cancer site. Among those with adequate staging who
      were alive after postoperative 90 days, 3-year survival was similar for curative
      compared with palliative operations (P = 0.64). CONCLUSIONS: Improved capacity
      for both therapeutic and palliative cancer care is needed to achieve better
      outcomes by more appropriate allocation of surgery with respect to the goal of
      treatment.

PMID- 30095204
TI  - miR-370 promotes high glucose-induced podocyte injuries by inhibiting angiotensin
      II type 1 receptor-associated protein.
AB  - miRNAs expression profiles in podocyte injuries have been reported in different
      models in vivo and in vitro. In the present study, miR-370 was elevated in high
      glucose-stimulated podocyte, and the post-transcriptional mechanism of miR-370
      was investigated in high glucose-induced podocyte injuries. The gene and protein
      levels were assayed by RT-qPCR and Western blotting, respectively. Annexin V
      fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining was used to
      evaluate the apoptosis in high glucose-stimulated podocyte. The targeted genes
      were predicted by a bioinformatics algorithm and confirmed by a dual luciferase
      reporter assay. The results demonstrated that over-activation of miR-370 was
      verified in high glucose-treated podocytes, while miR-370 repression protected
      against high glucose-induced apoptosis, cell membrane, and DNA damage in
      podocytes. We also found that AGTRAP as a direct target of miR-370 served as an
      opposite effect to miR-370, and overexpression of AGTRAP blocked high glucose
      induced podocytes dysfunction. In conclusions, high glucose-induced podocytes
      damage by activating miR-370 signaling targeted to inhibit the expression of
      AGTRAP, representing a novel and promising therapeutic target for the treatment
      of DN.

PMID- 30095202
TI  - Copy number variant discrepancy resolution using the ClinGen dosage sensitivity
      map results in updated clinical interpretations in ClinVar.
AB  - Conflict resolution in genomic variant interpretation is a critical step toward
      improving patient care. Evaluating interpretation discrepancies in copy number
      variants (CNVs) typically involves assessing overlapping genomic content with
      focus on genes/regions that may be subject to dosage sensitivity
      (haploinsufficiency (HI) and/or triplosensitivity (TS)). CNVs containing dosage
      sensitive genes/regions are generally interpreted as "likely pathogenic" (LP) or
      "pathogenic" (P), and CNVs involving the same known dosage sensitive gene(s)
      should receive the same clinical interpretation. We compared the Clinical Genome
      Resource (ClinGen) Dosage Map, a publicly available resource documenting known HI
      and TS genes/regions, against germline, clinical CNV interpretations within the
      ClinVar database. We identified 251 CNVs overlapping known dosage sensitive
      genes/regions but not classified as LP or P; these were sent back to their
      original submitting laboratories for re-evaluation. Of 246 CNVs re-evaluated, an
      updated clinical classification was warranted in 157 cases (63.8%); no change was
      made to the current classification in 79 cases (32.1%); and 10 cases (4.1%)
      resulted in other types of updates to ClinVar records. This effort will add
      curated interpretation data into the public domain and allow laboratories to
      focus attention on more complex discrepancies.

PMID- 30095205
TI  - Predicting cancer outcome: Artificial intelligence vs. pathologists.

PMID- 30095206
TI  - Crystal Structure of PigA: A Prolyl Thioester-Oxidizing Enzyme in Prodigiosin
      Biosynthesis.
AB  - Prodigiosin is an intensely red pigment comprising three pyrroles. The
      biosynthetic pathway includes a two-step proline oxidation catalyzed by
      phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PigA), with
      flavin adenine dinucleotide (FAD) as its cofactor. The enzyme is crystallized in
      the apo form and in complex with FAD and proline. As an acyl coenzyme A
      dehydrogenase (ACAD) family member, the protein folds into a beta-sheet flanked
      by two alpha-helical domains. PigA forms a tetramer, which is consistent with
      analytical ultracentrifugation results. FAD binds to PigA in a similar way to
      that in the other enzymes of the ACAD family. The variable conformations of loop
      beta4-beta5 and helix alphaG correlate well with the structural flexibility
      required for substrate entrance to the Re side of FAD. Modeling with PigG, the
      acyl carrier protein, suggests a reasonable mode of interaction with PigA. The
      structure helps to explain the proline oxidation mechanism, in which Glu244 plays
      a central role by abstracting the substrate protons. It also reveals a plausible
      pocket for oxygen binding to the Si side of FAD.

PMID- 30095207
TI  - Changes in telomere length with aging in human neurons and glial cells revealed
      by quantitative fluorescence in situ hybridization analysis.
AB  - AIM: The telomere is a structure present at the ends of chromosomes, and is known
      to shorten with aging and successive rounds of cell division. However, very
      little is known about telomere attrition in post-mitotic cells, such as neurons.
      METHODS: Using our originally developed quantitative fluorescence in situ
      hybridization method, we analyzed age-dependent alterations of telomere length in
      three types of cells in the human cerebrum: neurons and glial cells in both the
      gray and white matter. RESULTS: In adults, telomeres were significantly longer in
      neurons than in glial cells, whereas in infants, telomere lengths did not differ
      among the three cell types. No aging-related telomere attrition was evident in
      neurons. However, the telomeres of glial cells were shorter in older individuals
      than in younger individuals, and attrition was more rapid in the white matter
      than in the gray matter. CONCLUSIONS: The present results suggest that the
      telomeres of neurons remain stable throughout life, whereas telomeres in white
      matter glial cells become significantly shorter with age. Examination of adults
      showed no significant correlation between telomere length and age in the three
      cell types. Although the present study was cross-sectional, the results suggest
      that telomere shortening before adolescence contributes to the significant
      decrease of telomere length in white matter glial cells. The present findings in
      normal cerebral tissues will be informative for future studies of telomere
      stability in the diseased brain. Geriatr Gerontol Int 2018; 18: 1507-1512.

PMID- 30095208
TI  - Novel DLX3 variants in amelogenesis imperfecta with attenuated tricho-dento
      osseous syndrome.
AB  - OBJECTIVES: Variants in DLX3 cause tricho-dento-osseous syndrome (TDO, MIM
      #190320), a systemic condition with hair, nail and bony changes, taurodontism and
      amelogenesis imperfecta (AI), inherited in an autosomal dominant fashion.
      Different variants found within this gene are associated with different
      phenotypic presentations. To date, six different DLX3 variants have been reported
      in TDO. The aim of this paper was to explore and discuss three recently uncovered
      new variants in DLX3. SUBJECTS AND METHODS: Whole-exome sequencing identified a
      new DLX3 variant in one family, recruited as part of an ongoing study of genetic
      variants associated with AI. Targeted clinical exome sequencing of two further
      families revealed another new variant of DLX3 and complete heterozygous deletion
      of DLX3. For all three families, the phenotypes were shown to consist of AI and
      taurodontism, together with other attenuated features of TDO. RESULTS: c.574delG
      p.(E192Rfs*66), c.476G>T (p.R159L) and a heterozygous deletion of the entire DLX3
      coding region were identified in our families. CONCLUSION: These previously
      unreported variants add to the growing literature surrounding AI, allowing for
      more accurate genetic testing and better understanding of the associated clinical
      consequences.

PMID- 30095209
TI  - Fast Exfoliation and Functionalisation of Two-Dimensional Crystalline Carbon
      Nitride by Framework Charging.
AB  - Two-dimensional (2D) layered graphitic carbon nitride (gCN) nanosheets offer
      intriguing electronic and chemical properties. However, the exfoliation and
      functionalisation of gCN for specific applications remain challenging. We report
      a scalable one-pot reductive method to produce solutions of single- and few-layer
      2D gCN nanosheets with excellent stability in a high mass yield (35 %) from
      polytriazine imide. High-resolution imaging confirmed the intact crystalline
      structure and identified an AB stacking for gCN layers. The charge allows
      deliberate organic functionalisation of dissolved gCN, providing a general route
      to adjust their properties.

PMID- 30095211
TI  - Microbiota of the conjunctival sac of 120 healthy cats.
AB  - OBJECTIVES: To describe the bacterial and fungal microbiota of the conjunctiva
      and factors influencing these microbiota of healthy cats. To evaluate the
      antimicrobial resistance profile and discuss the use of appropriate antimicrobial
      drugs. ANIMALS STUDIED: One hundred and twenty healthy cats PROCEDURES:
      Conjunctival samples with dry or premoistened swabs were obtained from both eyes
      and cultured for aerobic and anaerobic bacteria and fungi. In vitro bacterial,
      susceptibility testing was performed. The effects of age, sex, breed, season,
      living environment, and sample collection technique on the frequency and
      composition of microbial isolation were evaluated. RESULTS: In 49 of 120 cats
      (40.8%) and 73 of 240 swabs (30.4%), microorganisms were isolated. Of the
      isolates, 71% (61/86) were Gram-positive bacteria, 26% (22/86) were Gram-negative
      bacteria, and 3% (3/86) were fungi. Staphylococcus felis (17/86; 19.8%) was the
      most commonly isolated species. Moraxella osloensis (5/86; 5.8%) was the most
      frequent Gram-negative species. The season had a statistically significant
      influence (P = 0.04) on the frequency of isolation. The use of premoistened swabs
      increased the rate of Gram-positive bacterial detection significantly (P = 0.03).
      The in vitro susceptibility testing showed high efficacy of chloramphenicol,
      gentamicin, pradofloxacin, and enrofloxacin. CONCLUSIONS: The isolated microbiota
      aligns with previous studies performed in other countries, although the
      microbiota of cats in the present study showed wider bacterial diversity, and
      more Gram-negative species were isolated. Swab sampling should be performed with
      premoistened swabs. The topical antimicrobials gentamicin and chloramphenicol are
      suitable therapeutics for first-line treatment.

PMID- 30095210
TI  - Enterically delivered insulin tregopil exhibits rapid absorption characteristics
      and a pharmacodynamic effect similar to human insulin in conscious dogs.
AB  - AIMS: Current therapy fails to emulate rapid (first-phase) insulin release in
      relation to a meal, a key defect in types 1 and 2 diabetes. We aimed to quantify
      the pharmacokinetic (PK) and pharmacodynamic (PD) profile of insulin tregopil, an
      enterically-absorbed insulin analog that restores the normal distribution of
      insulin between the hepatic portal and peripheral circulations. MATERIALS AND
      METHODS: The PK and PD profiles of insulin tregopil were studied in overnight
      fasted, catheterized, conscious canines using four approaches: (1) equimolar
      intraportal infusions of tregopil vs human insulin; (2) escalating doses of oral
      tregopil; (3) identical, consecutive enteric doses of tregopil; and (4)
      comparison of oral tregopil to inhaled and subcutaneous human insulin
      administration. RESULTS: Equimolar intraportal infusions of tregopil and human
      insulin resulted in very similar PK profiles and PD profiles were nearly
      identical. Enteric delivery of tregopil brought about rapid absorption with tmax
      = 20 minutes in most cases. Median tmax was 20 minutes for oral tregopil and
      inhaled insulin and 88 minutes for subcutaneous human insulin. The time required
      for arterial plasma insulin levels to return to baseline was approximately 90,
      210 and 360 minutes for oral tregopil, inhaled insulin and subcutaneous insulin,
      respectively. CONCLUSIONS: Enterically delivered tregopil is rapidly absorbed and
      restores a portal-to-peripheral vascular distribution. These characteristics
      should improve postprandial hyperglycaemia in types 1 and 2 diabetes.

PMID- 30095212
TI  - Retrospective analysis of ocular neuropathies in diabetic dogs following cataract
      surgery.
AB  - OBJECTIVES: To describe and compare the cumulative incidence and clinical
      progression of ocular neuropathies in diabetic dogs vs nondiabetic dogs following
      cataract surgery. METHODS: Medical records of 196 diabetic and 442 nondiabetic
      dogs who underwent cataract surgery between 2004 and 2015 were reviewed. The
      percentage of patients affected by neuropathy and potential risk factors were
      compared between groups. RESULTS: Patients with diabetes mellitus (DM) were 20.4
      times more likely to develop an ocular neuropathy than patients without DM
      (12.24% vs 0.68%). Twenty-four diabetic patients were affected by
      mononeuropathies or polyneuropathies including Horner's syndrome (n = 20), facial
      neuropathy (n = 5), and neurogenic keratoconjunctivitis sicca (NKCS) (n = 5). The
      odds of a diabetic patient developing Horner's syndrome and NKCS were 86.3 and
      20.7 times higher than a nondiabetic patient, respectively. The average duration
      of DM prior to diagnosis of neuropathy was 659 days (range 110-2390 days; median
      559 days). Complete resolution was achieved in 10 of 22 neuropathies (45%) within
      an average of 248 days (range 21-638 days; median 187 days) after diagnosis.
      CONCLUSIONS: The odds of developing an ocular neuropathy, specifically Horner's
      syndrome and NKCS, are statistically higher in diabetic patients compared to
      nondiabetic patients. Neuropathies were observed as a long-term complication in
      this group of diabetic patients, and complete resolution of the neuropathy was
      observed in less than half of the affected population.

PMID- 30095214
TI  - miR-185 affected the EMT, cell viability and proliferation via DNMT1/MEG3 pathway
      in TGF-beta1-induced renal fibrosis.
AB  - Kidney fibrosis is usually the final manifestation of a wide variety of renal
      diseases. Recent years, research reported that lncRNAs played important roles in
      a variety of human diseases. However, the role and underlying mechanisms of
      lncRNAs in kidney fibrosis were complicated and largely unclear. In our study, we
      constructed the cell model of renal fibrosis in HK2 cells using TGF-beta1 and
      found that lncRNA MEG3 was down-regulated in TGF-beta1-induced renal fibrosis. We
      then found that overexpressed MEG3 inhibited the TGF-beta1-induced promotion of
      EMT, cell viability and proliferation. Furthermore, we demonstrated that DNMT1
      regulated the MEG3 expression via altering the CpGs methylation level of MEG3
      promoter in TGF-beta1-induced renal fibrosis. In addition, we further revealed
      that miR-185 could regulated the DNMT1 expression and thus, modulating the MEG3
      in TGF-beta1-induced renal fibrosis. Ultimately, our study illustrated that the
      modulation of the miR-185/ DNMT1/ MEG3 pathway exerted important roles in TGF
      beta1-induced renal fibrosis. In summary, our finding displayed a novel
      regulatory mechanism for TGF-beta1-induced renal fibrosis, which provided a new
      potential therapeutic target for renal fibrosis.

PMID- 30095215
TI  - miR-182-5p overexpression inhibits chondrogenesis by down-regulating PTHLH.
AB  - BACKGROUND: Human bone marrow mesenchymal stem cells (hBM-MSC) have the ability
      of differentiating into chondrocytes and osteoblasts. miR-182-5p promotes
      osteoclastogenesis and bone metastasis by up-regulating the expression of
      parathyroid hormone-like hormone (PTHLH). However, the function of miR-182-5p in
      chondrogenesis is still unknown. METHODS: Mimic or inhibitor of miR-182-5p were
      used to upregulate or knock-down miR-182-5p expression respectively. We analyzed
      chondrogenesis by Safranin O staining and BlyscanTM Sulfated Glycosaminoglycan
      Assay. Immunohistochemistry, real-time PCR and western bolts were used to detect
      related makers. RESULTS: miR-182-5p overexpression inhibited chondrogenesis. Dual
      luciferase reporter assay indicated that PTHLH was one of the target genes of miR
      182-5p. Further studies showed that miR-182-5p overexpression down-regulated the
      expression of SOX-9 and COL2A1, but up-regulated COL1A1 and COL10A1.
      Consistently, miR-182-5p knock-down had the opposite effects. This effect of miR
      182-5p in BM-MSCs can be rescued by PTHLH overexpression. CONCLUSION: miR-182-5p
      may play a negative role in chondrogenesis by down-regulating PTHLH.

PMID- 30095216
TI  - Pentraxin 3 promotes cardiac differentiation of mouse embryonic stem cells
      through JNK signaling pathway.
AB  - Cardiovascular disease is a leading cause of death worldwide, requiring the
      development of new therapeutic strategies including stem cell therapy. Pentraxins
      (PTXs) are a superfamily of proteins highly involved in different myocardial
      disorders, and thus this study aimed to identify the modulation of long pentraxin
      3 (PTX3) in the differentiation of mouse embryonic stem cells (mESCs) toward
      cardiomyocytes. Cell toxicity of PTX3 was detected by MTT and LDH assays in
      mESCs. Embryoid bodies (EBs) were differentiated using hanging drop method, and
      the beating was observed under microscope. Expressional levels of early cardiac
      progenitor marker genes were assessed by qRT-PCR. Expression of marker proteins
      in early myocardial development and the activation of JNK signaling pathway was
      evaluated by Western blot. PTX3 treatment at 50 ng/mL significantly promoted the
      expression of cardiac-specific marker genes including Nkx2.5, Mef2c, Tbx5, dHand,
      and alphaMHC, and increased the expression of cardiac maturity indicative markers
      including connexin 43 and troponin C1. PTX3 enhanced the phosphorylation of JNK
      across the incubation duration, whereas the activation of p38 remained the same
      as control group. Co-treatment of JNK signaling pathway inhibitor SP600125
      impaired the PTX3-promoted transcription of Nkx2.5, Mef2c, Tbx5, dHand, and
      alphaMHC. This study revealed the promotion of PTX3 in the differentiation of
      mESCs into cardiomyocytes and the underlying mechanism.

PMID- 30095213
TI  - Reversible deficits in apical transporter trafficking associated with deficiency
      in diacylglycerol acyltransferase.
AB  - Deficiency in diacylglycerol acyltransferase (DGAT1) is a rare cause of neonatal
      diarrhea, without a known mechanism or in vitro model. A patient presenting at
      our institution at 7 weeks of life with failure to thrive and diarrhea was found
      by whole-exome sequencing to have a homozygous DGAT1 truncation mutation.
      Duodenal biopsies showed loss of DGAT1 and deficits in apical membrane
      transporters and junctional proteins in enterocytes. When placed on a very low
      fat diet, the patient's diarrhea resolved with normalization of brush border
      transporter localization in endoscopic biopsies. DGAT1 knockdown in Caco2-BBe
      cells modeled the deficits in apical trafficking, with loss of apical DPPIV and
      junctional occludin. Elevation in cellular lipid levels, including diacylglycerol
      (DAG) and phospholipid metabolites of DAG, was documented by lipid analysis in
      DGAT1 knockdown cells. Culture of the DGAT1 knockdown cells in lipid-depleted
      media led to re-establishment of occludin and return of apical DPPIV. DGAT1 loss
      appears to elicit global changes in enterocyte polarized trafficking that could
      account for deficits in absorption seen in the patient. The in vitro modeling of
      this disease should allow for investigation of possible therapeutic targets.

PMID- 30095217
TI  - Programming of the Beige Phenotype in White Adipose Tissue of Adult Mice by Mild
      Resveratrol and Nicotinamide Riboside Supplementations in Early Postnatal Life.
AB  - SCOPE: Resveratrol (RSV) and nicotinamide riboside (NR) are food compounds with
      anti-obesity actions in adult rodents. Here, the long-term effects of RSV and NR
      mild supplementation throughout lactation on adiposity-related parameters and the
      appearance of the beige phenotype in white adipose tissue (WAT) in adulthood are
      assessed. METHODS AND RESULTS: Newborn mice received orally RSV or NR from day 2
      to 20 of life. Control littermates received the vehicle. All animals are weaned
      onto a chow diet on day 21. On day 90, half the animals of each group are
      assigned to a high-fat diet (HFD) for 10 weeks, while the other remained on a
      normal-fat diet. Energy-balance-related parameters, blood parameters, and gene
      expression and immunohistochemical analysis of WAT are assessed. Treated male
      mice show an improved response to the HFD, such as delayed body weight gain, a
      blunted increase in the plasma leptin/adiponectin ratio, and a decreased
      lipolytic response, together with signs of white-to-brown fat remodeling in
      inguinal WAT. These effects are absent in female mice. CONCLUSION: RSV and NR
      supplementations in early postnatal life affect WAT's thermogenic/oxidative
      transcriptional phenotype and metabolic responses in adulthood, with upregulatory
      and beneficial effects evidenced in male animals.

PMID- 30095218
TI  - Temporally Programmed Disassembly and Reassembly of C3Ms.
AB  - Responsive materials, which can adapt and operate autonomously under dynamic
      conditions, are a stepping stone towards functional, life-like systems inspired
      by fueled self-assembly processes in nature. Complex coacervate core micelles
      (C3Ms) comprising oppositely charged macromolecules constitute a novel class of
      polymeric micelles ideally suited for use as responsive nanoscopic delivery
      vehicles of hydrophilic and hydrophobic cargo. To fully exploit their potential,
      it is important that the C3Ms form and fall apart in an autonomous fashion as
      orchestrated by dynamic cues in their environment. Herein a means to temporally
      program the self-regulated C3M coassembly pathway, using a modulated base
      catalyzed feedback system, is presented. Incorporated in the C3Ms is a pH
      responsive polyfluorene-based conjugated polyelectrolyte (CPF) as a building
      block and trace amounts of a molecular sensor (doxorubicin HCl) as cargo, both of
      which report on micellar coassembly and disassembly via binding-induced
      fluorescence quenching. CPF additionally reports on the pH of its
      microenvironment as its pH-dependent conformational states are mirrored in the
      transitions of its vibronic bands. This experimental design enables one to
      monitor solution pH, C3M disassembly and reassembly, as well as cargo release and
      recapture noninvasively in a closed system with real time florescence
      experiments.

PMID- 30095219
TI  - Lenalidomide, a blockbuster drug for the treatment of multiple myeloma:
      Semipreparative separation through supercritical fluid chromatography and
      vibrational circular dichroism spectroscopy.
AB  - Semipreparative separation of lenalidomide has been performed through
      supercritical fluid chromatography. In regard to retention and resolution of
      lenalidomide, effects of chromatographic conditions, such as chiral stationary
      phases, organic co-solvents, mobile phases, and column temperature, have been
      studied in detail. Amylose tris(3, 5-dimethylphenylcarbamate)-coated and the
      single-urea-bound beta-cyclodextrin chiral stationary phases exhibited good
      separation performances for lenalidomide in the CO2 /methanol mixture. Then, a
      comparative study of semipreparative separation of lenalidomide has been carried
      out on these two chiral stationary phases. As indicated, separation of
      lenalidomide on the beta-cyclodextrin-bound column was much better than the
      other. Under the optimized conditions, the loading per injection was 30 mg, the
      cycle time was 5 min, and the recoveries of two enantiomers were about 81.7 and
      79.5%, respectively. Moreover, the vibrational circular dichroism spectrum of the
      first-eluted enantiomer in d6 -dimethylsulfoxide solution was consistent with the
      calculated pattern based on the S configuration, revealing that it should be (S)
      (-)-lenalidomide. Briefly, this separation method through supercritical fluid
      chromatography might provide favorable information for rapid separation,
      enantioselective assessment, and absolute configurations of chiral
      pharmaceuticals.

PMID- 30095221
TI  - Bioavailability of mercury in power plant wastewater and ambient river samples:
      Evidence that the regulation of total mercury is not appropriate.
AB  - Mercury (Hg) is a neurotoxin that can cause debilitating effects to human and
      environmental receptors under high exposure conditions. For industrial and
      municipal point sources that discharge Hg, wastewater limitations on total Hg
      (THg) concentrations or loads are typical. While this regulatory practice
      provides simplicity for regulated industry and water resource agencies (i.e., for
      analytical detection and reporting purposes), it ignores the important
      considerations of speciation and bioavailability. In this study, water samples
      were collected from multiple power plant wastewater, simulated mixing zone, and
      ambient river locations (N = 10 to 20) and were analyzed for bioavailable Hg
      forms (methylmercury and acid-labile Hg, or BHg), THg, and dissolved Hg. The
      median concentration of THg in wastewater, mixing zone, and ambient river samples
      was 7.1, 5.3, and 2.3 ng/L, respectively. The percentages of THg as BHg (median
      values) were 18.7%, 29.3%, and 8.5% for wastewater, mixing zone, and ambient
      river samples. The percentages of methylmercury (MeHg) as THg were not
      statistically different between paired ambient and mixing zone samples (P >
      0.05); this result indicates that wastewater did not increase the MeHg fraction
      when mixed with ambient water. Multiple regression analysis indicated that
      variation in THg for combined wastewater and mixing zone samples could be
      adequately explained by pooled water quality parameters (total suspended solids,
      total dissolved solids, sulfate, total organic carbon, pH, specific conductivity;
      r2  = 0.51; P < 0.05); however, no significant regression relationships were
      apparent for the percentage of BHg. These results, at least for the wastewater
      samples evaluated, indicate that regulating THg is likely overly conservative,
      and mechanisms to regulate the bioavailable forms of Hg are needed. If Hg fish
      tissue monitoring data indicate that concentrations are less than consumption
      thresholds, metal translator methodologies or bioavailability-based criterion
      techniques (as currently used for non-Hg trace elements) should be allowed for
      Hg. Integr Environ Assess Manag 2018;00:000-000. (c) 2018 SETAC.

PMID- 30095220
TI  - Edge-Terminated MoS2 Nanoassembled Electrocatalyst via In Situ Hybridization with
      3D Carbon Network.
AB  - Transition metal dichalcogenides, especially MoS2 , are considered as promising
      electrocatalysts for hydrogen evolution reaction (HER). Since the physicochemical
      properties of MoS2 and electrode morphology are highly sensitive factor for HER
      performance, designed synthesis is highly pursued. Here, an in situ method to
      prepare a 3D carbon/MoS2 hybrid catalyst, motivated by the graphene ribbon
      synthesis process, is reported. By rational design strategies, the hybrid
      electrocatalysts with cross-connected porous structure are obtained, and they
      show a high HER activity even comparable to the state-of-the-art MoS2 catalyst
      without appreciable activity loss in long-term operations. Based on various
      physicochemical techniques, it is demonstrated that the synthetic procedure can
      effectively guide the formation of active site and 3D structure with a
      distinctive feature; increased exposure of active sites by decreased domain size
      and intrinsically high activity through controlling the number of stacking
      layers. Moreover, the importance of structural properties of the MoS2 -based
      catalysts is verified by controlled experiments, validating the effectiveness of
      the designed synthesis approach.

PMID- 30095222
TI  - The Proteome of Enchytraeus crypticus-Exposure to CuO Nanomaterial and CuCl2 -in
      Pursue of a Mechanistic Interpretation.
AB  - The transcriptome of the ecotoxicological model Enchytraeus crypticus (known as
      potworm) is well studied, but the downstream changes at the protein level
      remained a gap. Changes in the protein regulation following exposure to CuO
      nanomaterial (NM) and Cu salt (CuCl2 ) are investigated. HPLC-MS/MS using tandem
      mass tags is used. CuO NM elicits higher number of differentially expressed
      proteins (DEPs) compared to CuCl2 with little to no overlap of proteins. CuO NM
      causes more stress response mechanisms, with good agreement between DEPs, genes,
      and metabolites. CuCl2 causes higher impact in shorter time periods, but
      organisms have conserved mechanisms (constitutive genes) that allow Cu handling
      and detoxification. CuO NM causes higher impact after a longer exposure period,
      inducing regulation of facultative genes with a whole differentiated paradigm and
      cascade. This could be due to different issues: 1) the cell uptake route is
      different for Cu NM and Cu ions, 2) internalized Cu NM can result in a "Trojan
      horse" effect, 3) the cascade of events occurs in a different time order, and 4)
      the organism uptake is different between life stages, i.e., cocoons thickened
      surface protects the entry of NM and juveniles have facilitated entry via
      tegument. The data have been deposited to the ProteomeXchange with identifier
      PXD010647.

PMID- 30095223
TI  - Reintervention following stage 1 palliation: A report from the NPC-QIC Registry.
AB  - BACKGROUND: Single ventricle heart disease with aortic arch hypoplasia has high
      morbidity and mortality, with the greatest risk after stage 1 palliation.
      Residual lesions often require catheter-based or surgical reintervention to
      minimize risk. We sought to describe the types, frequency, and risk factors for
      re-intervention between stage 1 and stage 2 palliation, utilizing the National
      Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) registry.
      METHODS: The NPC-QIC registry, consisting of patients discharged after stage 1
      palliation, was queried. Hybrid stage 1 palliation patients were excluded from
      this study. The primary risk factor was shunt type and the primary outcome was re
      intervention. RESULTS: Of 1156 patients, (50%) had re-intervention. There was no
      difference in total rate of re-intervention by shunt type (BT shunt 52% vs. RVPA
      shunt 48%; P = .17). Patients with a BT shunt had increased re-intervention
      during stage 1 hospitalization (P =.002). During the interstage period, following
      discharge from stage 1 palliation, patients with a BT shunt had increased aortic
      arch re-intervention (P < .005), while patients with an RVPA shunt had increased
      re-intervention on the shunt and the pulmonary arteries (P = .02). Postoperative
      mechanical ventilation >14 d (P < .01) was the only risk factor associated with
      re-intervention by multivariable analysis, regardless of shunt type. CONCLUSIONS:
      Re-intervention between stage I and stage 2 palliation is common. There is no
      difference in cumulative frequency of re-intervention between shunt types, though
      types and timing of re-intervention varied between shunt types. Longitudinal
      assessment of the NPC-QIC database is important to identify long term outcomes of
      patients requiring re-intervention.

PMID- 30095224
TI  - Naphthalene diimide-derivatives G-quadruplex ligands induce cell proliferation
      inhibition, mild telomeric dysfunction and cell cycle perturbation in U251MG
      glioma cells.
AB  - In the present paper, the biological effects of three different naphthalene
      diimides (NDIs) G-quadruplex (G4) ligands (H-NDI-Tyr, H-NDI-NMe2, and tetra-NDI
      NMe2) were comparatively evaluated to those exerted by RHPS4, a well
      characterized telomeric G4-ligand, in an in vitro model of glioblastoma. Data
      indicated that NDIs were very effective in blocking cell proliferation at
      nanomolar concentrations, although displaying a lower specificity for telomere
      targeting compared to RHPS4. In addition, differently from RHPS4, NDIs failed to
      enhance the effect of ionizing radiation, thus suggesting that additional targets
      other than telomeres could be involved in the strong NDI-mediated anti
      proliferative effects. In order to test telomeric off-target action of NDIs, a
      panel of genes involved in tumor progression, DNA repair, telomere maintenance,
      and cell-cycle regulation were evaluated at transcriptional and translational
      level. Specifically, the compounds were able to cause a marked reduction of TERT
      and BCL2 amounts as well as to favor the accumulation of proteins involved in
      cell cycle control. A detailed cytofluorimetric analysis of cell cycle
      progression by means of bromodeoxyuridine (BrdU) incorporation and staining of
      phospho-histone H3 indicated that NDIs greatly reduce the progression through S
      phase and lead to G1 accumulation of BrdU-positive cells. Taken together, these
      data indicated that, besides effects on telomeres and oncogenes such as Tert and
      Bcl2, nanomolar concentrations of NDIs determined a sustained block of cell
      proliferation by slowing down cell cycle progression during S-phase. In
      conclusion, our data indicate that NDIs G4-ligands are powerful antiproliferative
      agents, which act through mechanisms that ultimately lead to altered cell-cycle
      control.

PMID- 30095225
TI  - Dye-Anchored MnO Nanoparticles Targeting Tumor and Inducing Enhanced Phototherapy
      Effect via Mitochondria-Mediated Pathway.
AB  - Phototherapy is a promising treatment method for cancer therapy. However, the
      various factors have greatly restricted phototherapy development, including the
      poor accumulation of photosensitizer in tumor, hypoxia in solid tumor tissue and
      systemic phototoxicity. Herein, a mitochondrial-targeted multifunctional dye
      anchored manganese oxide nanoparticle (IR808@MnO NP) is developed for enhancing
      phototherapy of cancer. In this nanoplatform, IR808 as a small molecule dye acts
      as a tumor targeting ligand to make IR808@MnO NPs with capacity to actively
      target tumor cells and relocate finally in the mitochondria. Meanwhile,
      continuous production of oxygen (O2 ) and regulation of pH induced by the high
      reactivity and specificity of MnO NPs toward mitochondrial endogenous hydrogen
      peroxide (H2 O2 ) could effectively modulate tumor hypoxia and lessen the tumor
      subacid environment. Large amounts of reactive oxide species (ROS) are generated
      during the reaction process between H2 O2 and MnO NPs. Furthermore, under laser
      irradiation, IR808 in IR808@MnO NPs turns O2 into a highly toxic singlet oxygen
      (1 O2 ) and generates hyperthermia. The results indicate that IR808@MnO NPs have
      the high efficiency of specific targeting of tumors, relieving tumor subacid
      environment, improving the tumor hypoxia environment, and generating large
      amounts of ROS to kill tumor cells. It is expected to have a wide application in
      treating cancer.

PMID- 30095226
TI  - Proteomic Profiling Analysis of Male Infertility in Spodoptera Litura Larvae
      Challenged with Azadirachtin and its Potential-Regulated Pathways in the
      Following Stages.
AB  - Biopesticides are considered as an alternative to synthetic pesticide with a
      focus on increasing agricultural productivity as well as maintaining the
      ecosystem. Prior to application, its potential mechanism should be clearly
      addressed. Here, the effects of azadirachtin on the reproductive behavior in male
      Spodoptera litura (Fabricius) are determined. To further explore its molecular
      mechanism, an iTRAQ (isobaric tags for relative and absolute quantitation) based
      approach is applied to identify the differentially expressed proteins regulated
      by azadirachtin at two developmental stages. The results demonstrate that many
      proteins in the pathway of focal adhesion are regulated to exert influences in
      detachment of cell attachment, the loss of cell-cell interactions and inducing
      apoptosis at pupal stage, and many proteins in adenosine monophosphate-activated
      protein kinase pathway are also changed at the adult stage after azadirachtin
      treatment as larvae. Moreover, based on their important roles, it is suggested
      that some proteins, such as ACTB-G1, ste20-related adaptor protein alpha, and
      regulatory-associated protein of mTOR (mTORC1) could serve as potential target
      proteins of azadirachtin to induce male infertility. The results of this study
      could provide evidence to illuminate the mechanism of male infertility induced by
      azadirachtin and potential targets for the development of environmentally
      friendly pesticides.

PMID- 30095227
TI  - Is pulse oximetry helpful for the early detection of critical congenital heart
      disease at high altitude?
AB  - OBJECTIVE: To assess the pulse oximetry as a method for screening critical
      congenital heart disease (CHD) in newborns. STUDY DESIGN: This is an
      observational, transversal, descriptive simple study. The pre-ductal and
      postductal saturation were taken in term newborns that fulfilled the criteria of
      inclusion and exclusion in the Hospital Gineco-Obstetrico Isidro Ayora (HGOIA) in
      Quito. These measurements were performed between the 24 and 48 h after birth.
      Those newborns that saturated less than 90% on initial pulse oximetry underwent 3
      successive measurements at 1-h intervals. Those who saturate less than 90% after
      3 measurements or have a difference higher than 3% in preductal saturation and
      postductal saturation (positive screening) underwent transthoracic
      echocardiography evaluate for CHD. RESULTS: Pulse oximetry from 963 newborns was
      evaluated. In Quito, at an altitude of 2820 meters above sea level (9252 feet),
      the mean preductal saturation was 92.76% (SD +/- 3) and the postductal
      saturation, 93.76% (SD +/- 4.7). Pulse oximetry in 53 patients (5.5%) was
      classified as a positive screening. No critical congenital heart diseases were
      found. Atrial septal defect (ASD) was the most common finding in a 46.94% (n =
      23), followed by the association of patent ductus arteriosus (PDA) and ASD with a
      12.24% (n = 6). CONCLUSION: In this cohort of patients who underwent screening
      pulse oximetry, no critical congenital heart diseases (CHD) were observed.
      However, identifying those with oxygen saturation less than 90% after 3
      successive measurements or a pre- and postductal oxygen difference of > 3%
      resulted in successful identification of ASD and PDA. It is necessary to
      implement new cutoff points in saturation values to identify critical cardiac
      anomalies in cities placed at a high altitude. The use of pulse oximetry should
      be recommended in all the newborns.

PMID- 30095228
TI  - Stereotactic body radiotherapy for central lung tumors: Finding the balance
      between safety and efficacy in the "no fly" zone.
AB  - BACKGROUND: Stereotactic body radiotherapy (SBRT) has emerged as a highly
      effective technique to treat medically inoperable non-small cell lung cancer
      (NSCLC). Doses must be chosen carefully when treating central lesions because of
      the potential for significant toxicity. This study reviews the outcomes of a
      cohort of patients with central lung tumors treated with SBRT. METHODS: We
      identified 18 patients (12 women, 6 men) with central lesions that were treated
      with SBRT at our institution. Overall survival and local, regional, and distant
      control rates were assessed by Kaplan-Meier methodology. Correlations with
      outcomes were determined by multivariate analysis via Cox regression models.
      RESULTS: Eighty-nine percent of patients had a pathological diagnosis of NSCLC.
      The median dose to the planning target volume was 40 Gy (range: 30-50) in five
      fractions, yielding a median biologic equivalent dose (BED10 ) of 72 (range: 48
      100). The median planning target volume was 34 cc (range: 13.3-89). Local control
      was 87% at one year. Median overall survival was 45 months, with a two-year rate
      of 61%. The two-year regional control rate was 87%. BED10 > 72 predicted improved
      progression-free survival, with one-year rates of 100% versus 40% with increased
      BED (P = 0.012). No grade 3 or higher acute or late toxicity was observed.
      CONCLUSIONS: Lung SBRT to central lesions is safe and effective when using five
      fraction regimens. BED10 < 72 predicted disease progression, highlighting the
      importance of choosing an effective dose fractionation scheme, which must in turn
      be balanced with potential toxicity.

PMID- 30095229
TI  - Crystal structure of the VanR transcription factor and the role of its unique
      alpha-helix in effector recognition.
AB  - VanR is a negative transcriptional regulator of bacteria that belongs to the PadR
      family and modulates the expression of vanillate transport and degradation
      proteins in response to vanillate. Although VanR plays a key role in the
      utilization of vanillate as a carbon source, it is barely understood how VanR
      recognizes its effector. Thus, our knowledge concerning the gene regulatory
      mechanism of VanR is limited. Here, we reveal the vanillate-binding mode of VanR
      through structural, biophysical, and mutational studies. Similar to other PadR
      family members, VanR forms a functional dimer, and each VanR subunit consists of
      an N-terminal DNA-binding domain (NTD) and a C-terminal dimerization domain
      (CTD). One VanR dimer simultaneously binds two vanillate molecules using two
      interdomain cavities, as observed in PadR. In contrast to these common features,
      VanR contains an additional alpha-helix, alphai, that has not been found in other
      PadR family members. The alphai helix functions as an interdomain crosslinker
      that mediates interactions between the NTD and the CTD. In addition, the VanR
      specific alphai helix plays a key role in the formation of a unique effector
      binding site. As a result, the effector-binding mode of VanR is distinguishable
      from that of PadR in the location and accessibility of the effector-binding site
      as well as the orientation of its bound effector. Furthermore, we propose the DNA
      binding mode and vanillate-mediated transcriptional regulation mechanism of VanR
      based on comparative structural and mutational analyses. DATABASES: The atomic
      coordinates and the structure factors for VanR (PDB ID 5Z7B) have been deposited
      in the Protein Data Bank, www.pdb.org.

PMID- 30095230
TI  - The Feasibility and Effectiveness of PASS Plus, A Lay Health Worker Delivered
      Comprehensive Intervention for Autism Spectrum Disorders: Pilot RCT in a Rural
      Low and Middle Income Country Setting.
AB  - : The treatment gap for autism globally is high. Our previous PASS intervention,
      delivered by community based lay health workers, showed effectiveness. This
      article reports the development and evaluation of a new "PASS 'Plus'"
      intervention in a rural population in India. Using formative research methods, we
      supplemented the PASS intervention with additional (Plus) modules to address
      autism comorbidities. This is the first time that a rigorous methodology has been
      used to evaluate autism symptom outcomes in a low and middle-income country
      setting. 40 parent-child dyads were recruited in a pilot randomized controlled
      trial against usual care (mean age 65 months (34 boys); n = 19 PASS Plus, n = 21
      UC). 89% of intervention families partially or entirely completed the 12-session
      intervention. Intention to treat analysis showed a reduction in mean scores of
      autism symptom severity, though the confidence interval contains zero, (adjusted
      mean difference AMD -2.42 95% CI -7.75, 2.92; ES 0.22); large treatment effects
      on proximal outcomes of proportion of parent synchronous responses (AMD 0.35; 95%
      CI 0.18, 0.52; effect size ES 3.97) and proportion of child communication
      initiations with parent (AMD 0.17; 95% CI 0.03, 0.32; ES 1.02). Confidence
      intervals for effects on mutual shared attention (AMD 0.10; 95% CI -0.07, 0.27;
      ES 0.5) and co-morbid symptoms (AMD -9.0; 95% CI -24.26, 6.26; ES 0.32) contained
      zero. There were significant effects to improve parental mental health. PASS Plus
      shows good feasibility and adds to the evidence of the effectiveness of task
      sharing complex autism interventions to lay health workers in India. Autism Res
      2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc.
      LAY SUMMARY: This article describes the development of a comprehensive, community
      delivered, intervention for young children with autism, which combines a
      previously developed parent-mediated communication intervention with support for
      co-morbid problems like challenging behaviors and sensory sensitivities. The
      unique aspect of this intervention is that it can be delivered by community
      health workers, addressing the lack of specialists in low resource settings. Our
      study reports the encouraging findings of a pilot trial evaluating its
      feasibility and effectiveness.

PMID- 30095231
TI  - Age-dependent effects on sympathetic responsiveness in cardiac action potential
      conduction and calcium handling.

PMID- 30095232
TI  - A randomized controlled trial evaluating the Hebrew adaptation of the PEERS(r)
      intervention: Behavioral and questionnaire-based outcomes.
AB  - Social interaction deficits form a core characteristic of ASD that is commonly
      targeted through social-skill groups. The Program for the Education and
      Enrichment of Relational Skills (PEERS(r) ) is a well-established parent-assisted
      intervention for adolescents, which addresses key areas of social functioning.
      PEERS(r) has been mainly studied in North-America and its evaluations were mostly
      questionnaire based. The aim of the current study was to test the effectiveness
      of the adapted and translated Hebrew version of the PEERS(r) intervention in a
      randomized controlled trial, using behavioral measures of peer interaction, in
      addition to self, parent, and teacher reports. Forty-one participants with ASD
      and no intellectual impairment, aged 12-17 years, were randomly assigned to an
      immediate intervention or a delayed-intervention group. All participants were
      assessed before and after the immediate intervention, and again at follow up,
      after the delayed intervention took place. Results revealed intervention-related
      behavioral improvements on adolescents' engagement, question-asking, and physical
      arousal. Parental reports indicated improved social skills, and reduced ASD
      symptoms. Adolescents reported on more social encounters, greater empathy, and
      scored higher on social-skill knowledge. Most of these effects maintained at a 16
      week follow-up. Teacher reports' yielded effects only on pre-post intervention
      analysis. Adolescents' improvement on behavioral engagement predicted parent
      reported social skills improvement. Our findings support the effectiveness of the
      adapted Hebrew version of PEERS(r) for adolescents with ASD, through significant
      behavioral and questionnaire-based outcomes, which maintained at follow-up.
      Autism Res 2018, 11: 1187-1200. (c) 2018 International Society for Autism
      Research, Wiley Periodicals, Inc. LAY SUMMARY: Social-skills groups, which
      facilitate key social deficits characteristic of ASD, are a popular intervention
      for adolescents with ASD. Indeed, many treatment protocols have been published,
      and some have also been research validated. However, there have been inconsistent
      findings regarding the effectiveness of different protocols, in addition to
      limited findings of improvement beyond questionnaire reports. This study
      evaluated the Hebrew adaptation of the PEERS(r) intervention, a 16-weeks long
      program, which involves the parents as their adolescents' social coaches.
      Following the intervention, adolescents improved their social-skills,
      participated more in social encounters, reported greater empathy, and
      demonstrated higher social-skill knowledge. A live play-role assessment with an
      unfamiliar peer indicated that adolescents showed greater involvement, asked more
      questions and were more physically relaxed during the conversation. Improvements
      maintained 16 weeks after the intervention was completed.

PMID- 30095233
TI  - Re: Screening for ovarian cancer: imaging challenges and opportunities for
      improvement.

PMID- 30095234
TI  - Re: Differences in ultrasound features of papillations in unilocular-solid
      adnexal cysts: a retrospective international multicenter study. C. Landolfo, L.
      Valentin, D. Franchi, C. Van Holsbeke, R. Fruscio, W. Froyman, P. Sladkevicius,
      J. Kaijser, L. Ameye, T. Bourne, L. Savelli, A. Coosemans, A. Testa and D.
      Timmerman. Ultrasound Obstet Gynecol 2018; 52: 269-278.

PMID- 30095235
TI  - Re: In-utero aspiration vs expectant management of anechoic fetal ovarian cysts:
      open randomized controlled trial. C. Diguisto , N. Winer , G. Benoist , H.
      Laurichesse-Delmas , J. Potin , A. Binet , H. Lardy , B. Morel and F. Perrotin .
      Ultrasound Obstet Gynecol 2018; 52: 159-164.

PMID- 30095236
TI  - Computing the proportion of liveborn children with biventricular circulation
      after successful fetal aortic valvuloplasty.

PMID- 30095237
TI  - Intervention for fetal critical aortic stenosis: first step in a metamorphosis?

PMID- 30095238
TI  - Confidence intervals vs reference intervals for regression analysis: which one to
      use?

PMID- 30095239
TI  - Reply.

PMID- 30095240
TI  - Family history of immune conditions and autism spectrum and developmental
      disorders: Findings from the study to explore early development.
AB  - : Numerous studies have reported immune system disturbances in individuals with
      autism and their family members; however, there is considerable variability in
      findings with respect to the specific immune conditions involved, their timing,
      and the family members affected and little understanding of variation by autism
      subphenotype. Using data from the Study to Explore Early Development (SEED), a
      multi-site case-control study of children born 2003-2006 in the United States, we
      examined the role of family history of autoimmune diseases, asthma, and allergies
      in autism spectrum disorder (ASD) as well as other developmental disorders (DD).
      We investigated maternal immune conditions during the pregnancy period, as well
      as lifetime history of these conditions in several family members (mother,
      father, siblings, and study child). Logistic regression analyses included 663
      children with ASD, 984 children with DD, and 915 controls ascertained from the
      general population (POP). Maternal history of eczema/psoriasis and asthma was
      associated with a 20%-40% increased odds of both ASD and DD. Risk estimates
      varied by specific ASD subphenotypes in association with these exposures. In
      addition, children with ASD were more likely to have a history of
      psoriasis/eczema or allergies than POP controls. No association was observed for
      paternal history or family history of these immune conditions for either ASD or
      DD. These data support a link between maternal and child immune conditions and
      adverse neurodevelopmental outcomes, and further suggest that associations may
      differ by ASD phenotype of the child. Autism Res 2018., (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Using data from
      a large multi-site study in the US-the Study to Explore Early Development-we
      found that women with a history of eczema/psoriasis and asthma are more likely to
      have children with ASD or DD. In addition, children with ASD are more likely to
      have a history of psoriasis/eczema or allergies than typically developing
      children. These data support a link between maternal and child immune conditions
      and adverse neurodevelopmental outcomes.

PMID- 30095241
TI  - Initial description of the core ocular surface microbiome in dogs: Bacterial
      community diversity and composition in a defined canine population.
AB  - OBJECTIVE: To characterize the bacterial community residing on the conjunctiva of
      clinically healthy dogs. METHODS: Bacterial DNA from conjunctival swabs of 10
      dogs with normal ocular examinations (both OD and OS, n = 20) was extracted, and
      16S rRNA amplicons were sequenced using Illumina MiSeq 600. Resulting data were
      subjected to quality control steps, and analyzed for bacterial community richness
      and diversity, within- and between-group dissimilarity, and relative taxonomic
      composition. RESULTS: High-quality reads (2.22 million bp) resulted in a mean of
      159 068 sequences per sample. Bacterial community evenness and diversity was high
      when compared to other species, and did not significantly differ when samples
      were grouped by dogs or eyes. As expected, within-dog samples were more similar
      than between-dog samples. Taxonomic classification revealed that >95% of the
      community consisted of Firmicutes (34.9 +/- 8.8%), Actinobacteria (26.3 +/-
      7.1%), Proteobacteria (26.2 +/- 6.6%), and Bacteroidetes (9.4 +/- 2.4%). Key
      members of the dog ocular surface microbiome, found in all dogs and corresponding
      to >25% of all identified OTUs (operational taxonomic units), were part of the
      Bifidobacteriaceae, Lachnospiraceae, Moraxellaceae, Corynebacteriaceae families.
      Genera previously thought to account for the majority of the core ocular surface
      microbiome in the dog (Staphylococcus sp., Streptococcus sp., and Bacillus sp.)
      were associated with only 2.63% of overall reads. CONCLUSIONS: This study shows
      the feasibility of conjunctival swabs and high-throughput sequencing to profile
      the bacterial community structure of the canine ocular surface. A core ocular
      surface microbiome was identified for this canine population.

PMID- 30095242
TI  - Executive function predicts the visuospatial working memory in autism spectrum
      disorder and attention-deficit/hyperactivity disorder.
AB  - Children with autism spectrum disorder (ASD) and those with attention
      deficit/hyperactivity disorder (ADHD) always show working memory deficits.
      However, research findings on the factors that affected the working memory in ASD
      and ADHD were inconsistent. Thus, we developed the present study to investigate
      the association of executive function (EF) with the visuospatial working memory
      (VSWM) in ASD and ADHD. Three groups of participants were examined: 21 children
      with ASD, 28 children with ADHD and 28 typically developing (TD) children as the
      controls. All participants completed two tests: the Wisconsin Card Sorting Test
      (WCST) and the Corsi Block Tapping Test for measuring EF and VSWM, respectively.
      The WCST included four domains: categories achieved (CA), perseverative errors
      (PE), failures to maintain set (FMS), and total errors (TE). The findings
      indicated that (1) the ASD group showed poorer performance in VSWM than the ADHD
      and TD groups; (2) for the ASD group, VSWM was positively correlated with CA, and
      was negatively correlated with PE and TE; (3) for the ADHD group, FMS showed a
      negative relationship with VSWM; and (4) TE predicted the performance of VSWM in
      ASD group, while FMS predicted VSWM in ADHD group. The study results suggested
      that VSWM was impaired in ASD but not in ADHD. Also, the EF domains were
      differently correlated with the VSWM performance in ASD and ADHD. Our study
      suggests that we should consider different intervention targets of working memory
      and EF contributions in improving the cognitive capacity of ASD and ADHD. Autism
      Res 2018, 11: 1148-1156. (c) 2018 International Society for Autism Research,
      Wiley Periodicals, Inc. LAY SUMMARY: The present study compared the visuospatial
      working memory (VSWM) in three groups of children: autism (ASD), attention
      deficit/hyperactivity disorder (ADHD), and typically developed children (TD). The
      ASD group showed poorer VSWM than the ADHD and TD groups. The total error of
      executive function predicted the performance of VSWM in ASD, while failures to
      maintain set predicted VSWM in ADHD . These findings suggested that we should
      consider the different working memory and executive function training targets to
      increase cognitive capacity of ASD and ADHD.

PMID- 30095243
TI  - Free-Sustaining Three-Dimensional S235 Steel-Based Porous Electrocatalyst for
      Highly Efficient and Durable Oxygen Evolution.
AB  - A novel oxygen evolution reaction (OER) catalyst (3 D S235-P steel) based on a
      steel S235 substrate was successfully prepared by facile one-step surface
      modification. The standard carbon-manganese steel was phosphorized superficially,
      which led to the formation of a unique 3 D interconnected nanoporous surface with
      a high specific area that facilitated the electrocatalytically initiated oxygen
      evolution reaction. The prepared 3 D S235-P steel exhibited enhanced
      electrocatalytic OER activities in the alkaline regime, as confirmed by a low
      overpotential (326 mV at a 10 mA cm-2 ) and a small Tafel slope of 68.7 mV dec-1
      . Moreover, the catalyst was found to be stable under long-term usage conditions,
      functioning as an oxygen-evolving electrode at pH 13, as evidenced by the
      sufficient charge-to-oxygen conversion rate (faradaic efficiency: 82.11 and 88.34
      % at 10 and 5 mA cm-2 , respectively). In addition, it turned out that the chosen
      surface modification delivered steel S235 as an OER electrocatalyst that was
      stable under neutral pH conditions. Our investigation revealed that the high
      catalytic activities likely stemmed from the generated Fe/(Mn)
      hydroxide/oxohydroxides generated during the OER process. Phosphorization
      treatment therefore not only is an efficient way to optimize the electrocatalytic
      performance of standard carbon-manganese steel but also enables for the
      development of low-costing and abundant steels in the field of energy conversion.

PMID- 30095244
TI  - Synthesis and Characterization of Samarium-Substituted Molybdenum Diselenide and
      Its Graphene Oxide Nanohybrid for Enhancing the Selective Sensing of
      Chloramphenicol in a Milk Sample.
AB  - The electronic conductivity and electrocatalytic activity of metal chalcogenides
      are normally enhanced by following the ideal strategies such as
      substitution/doping of heterogeneous atoms and hybridization of highly conductive
      carbon supportive materials. Here, a rare earth element (samarium) was
      substituted with MoSe2 using the simple hydrothermal method. The lattice
      distortion due to the substitution of Sm3+ with MoSe2 was clearly observed by
      using high-resolution transmission electron microscopy analysis. As a
      consequence, the prepared SmMoSe2 nanorod was encapsulated with graphene oxide
      (GO) sheets by using ultrasonication process. Furthermore, the GO-encapsulated
      SmMoSe2 nanocomposite modified glassy carbon electrode (GO@SmMoSe2/GCE) was used
      for the sensing of chloramphenicol. The results showed that the GO@SmMoSe2/GCE
      revealed the superior electrocatalytic activity with low detection (5 nM) and
      sensitivity (20.6 MUA MUM-1 cm-2) to electrochemical detection of proposed
      analyte. It indicates that the substitution of Sm3+ and encapsulation of GO
      significantly increased both the electrical conductivity and electrocatalytic
      activity of MoSe2.

PMID- 30095245
TI  - Molecular Beacon Gold Nanosensors for Leucine-Rich Alpha-2-Glycoprotein-1
      Detection in Pathological Angiogenesis.
AB  - Leucine-rich alpha-2-glycoprotein-1 (Lrg1) is an emerging biomarker for
      angiogenesis. Its expression in ocular tissues is up-regulated in both human
      patients with proliferative diabetic retinopathy and rodent models of
      pathological angiogenesis. However, there is no existing sensor that allows
      visualization and monitoring of Lrg1 expression noninvasively and in real time.
      Herein, we report a nucleic acid-gold nanorod-based nanosensor for the
      noninvasive monitoring of cellular Lrg1 expression in angiogenesis. Specifically,
      this platform is constructed by covalently conjugating molecular beacons onto
      gold nanorods, which prequench the fluorophores on the molecular beacons. Upon
      intracellular entry and endosomal escape, the complexes interact with cellular
      Lrg1 mRNA through hybridization of the loop area of the molecular beacons. This
      complexation distances the fluorophores from nanorod and restores the prequenched
      fluorescence. The reliability of this platform is confirmed by examining the
      increased Lrg1 expression in migrating keratinocytes and the Lrg1 gene changes in
      different postnatal stages of mouse retinal vasculature growth in the mouse
      retina model.

PMID- 30095246
TI  - Novel Scaffolds for Dual Specificity Tyrosine-Phosphorylation-Regulated Kinase
      (DYRK1A) Inhibitors.
AB  - DYRK1A is one of five members of the dual-specificity tyrosine (Y)
      phosphorylation-regulated kinase (DYRK) family. The DYRK1A gene is located in the
      Down syndrome critical region and regulates cellular processes related to
      proliferation and differentiation of neuronal progenitor cells during early
      development. This has focused research on its role in neuronal degenerative
      diseases, including Alzheimer's and Down syndrome. Recent studies have also shown
      a possible role of DYRK1A in diabetes. Here we report a variety of scaffolds not
      generally known for DYRK1A inhibition, demonstrating their effects in in vitro
      assays and also in cell cultures. These inhibitors effectively block the tau
      phosphorylation that is a hallmark of Alzheimer's disease. The crystal structures
      of these inhibitors support the design of optimized and novel therapeutics.

PMID- 30095247
TI  - Organization of Amino Acids into Layered Supramolecular Secondary Structures.
AB  - The unique physiochemical properties and multiscale organization of layered
      materials draw the attention of researchers across a wide range of scientific
      disciplines. Layered structures are commonly found in diverse biological systems
      where they fulfill various functions. A prominent example of layered biological
      materials is the organization of proteins and polypeptides into the archetypal
      aggregated amyloidal structures. While the organization of proteins into amyloid
      structures was initially associated with various degenerative disorders, it was
      later revealed that proteins not related to any disease could also form identical
      layered assemblies. Thus, it appears that the ability of peptides and proteins to
      produce amyloid-like aggregates represents a generic property of polyamides to
      assemble into higher order fibrillar structures. In the aggregated state, the
      peptide backbone forms beta-sheet structures which are further organized into
      layered arrangements. We have recently extended the identified amyloidogenic
      building blocks to include not only peptides or proteins, but also single amino
      acids and other metabolites. High resolution spectroscopy and crystallography
      analyses confirm the clear potential of amino acids and other metabolites to form
      layered amyloid-like aggregates showing biophysical and biochemical properties
      similar to protein amyloids. Therefore, the generic propensity of peptides and
      proteins backbones to assemble into layered organizations may emanate from their
      basic building block, the amino acid. In this Account, we aim to introduce the
      concept of supramolecular beta-sheet organization of single amino acids and to
      present an analysis of their layered-structure organization based on single
      crystal structures. We demonstrate that, despite the different side-chains that
      considerably vary in their chemical properties, all coded amino acids display a
      layer-like assembly stabilized by alpha-amine to alpha-carboxyl H-bonds,
      resembling supramolecular beta-sheet structures, while the side-chains determine
      the higher order organization of the layers. Our work presents the first analysis
      of the beta-sheet propensity of single amino acids in their unbound form,
      indicating an evolutionary predisposition. We classify the amino acids beta-sheet
      propensity on the basis of the interlayer separation distance in the crystal
      packing, which correlates well with previously reported classifications based on
      various criteria, such as hydrophobicity, steric bulkiness, and folding. In
      addition, we demonstrate that the relative direction of alpha-amine to alpha
      carboxyl H-bonding pattern provides critical insights regarding the stabilization
      of parallel versus antiparallel beta-sheet structures by the various amino acids.
      Taken together, our analysis of amino acid crystals provides substantial
      information regarding protein folding and dynamics and could serve as basic rules
      set for the design of potential building blocks for molecular self-assembly to
      produce functional materials of tunable properties, an important objective of
      bottom-up nanotechnology.

PMID- 30095248
TI  - Correction to Electrodeformation-Based Biomechanical Chip for Quantifying Global
      Viscoelasticity of Cancer Cells Regulated by Cell Cycle.

PMID- 30095249
TI  - Influencing Early Stages of Neuromuscular Junction Formation through Glycocalyx
      Engineering.
AB  - Achieving molecular control over the formation of synaptic contacts in the
      nervous system can provide important insights into their regulation and can offer
      means for creating well-defined in vitro systems to evaluate modes of therapeutic
      intervention. Agrin-induced clustering of acetylcholine receptors (AChRs) at
      postsynaptic sites is a hallmark of the formation of the neuromuscular junction,
      a synapse between motoneurons and muscle cells. In addition to the cognate agrin
      receptor LRP4 (low-density lipoprotein receptor related protein-4), muscle cell
      heparan sulfate (HS) glycosaminoglycans (GAGs) have also been proposed to
      contribute to AChR clustering by acting as agrin co-receptors. Here, we provide
      direct evidence for the role of HS GAGs in agrin recruitment to the surface of
      myotubes, as well as their functional contributions toward AChR clustering. We
      also demonstrate that engineering of the myotube glycocalyx using synthetic HS
      GAG polymers can replace native HS structures to gain control over agrin-mediated
      AChR clustering.

PMID- 30095250
TI  - Systematic Exploration of the Role of a Modified Layer on the Separator in the
      Electrochemistry of Lithium-Sulfur Batteries.
AB  - As a significant constituent of lithium-sulfur batteries, the separator also
      exerts a considerable effect on the performance of the sulfur cathode. In our
      work, the mixture of acetylene black and multiwalled carbon nanotubes is
      uniformly applied onto the commercial polypropylene membranes to attain the
      modified separators. While investigating different samples, the underlying
      influence of the coating layer is systematically scrutinized on the
      electrochemical behaviors of sulfur cathodes, relying on the extensive
      electrochemical and structural measurements. During the charge/discharge process,
      the coating layer can function as the second current collector and drastically
      contribute to the improved lithium ions diffusion, determining the
      electrochemical kinetics of sulfur-involved reactions. Moreover, it is found that
      the thicker the layer, the faster the lithium ions diffuse. It should be noted
      that the coating layer also plays a role of the second sulfur reservoir to endow
      the ample active sites for sulfur and polysulfides, which is directly witnessed
      for the first time. Because of the positiveness and effectiveness of the modified
      layer on separators, the sulfur cathode can offer the superior cycling and rate
      performance to that with the original separator.

PMID- 30095251
TI  - Fabrication and Optimization of Fiber-Based Lithium Sensor: A Step toward
      Wearable Sensors for Lithium Drug Monitoring in Interstitial Fluid.
AB  - A miniaturized, flexible fiber-based lithium sensor was fabricated from low-cost
      cotton using a simple, repeatable dip-coating technique. This lithium sensor is
      highly suited for ready-to-use wearable applications and can be used directly
      without the preconditioning steps normally required with traditional ion
      selective electrodes. The sensor has a stable, rapid, and accurate response over
      a wide Li+ concentration range that spans over the clinically effective and the
      toxic concentration limits for lithium in human serum. The sensor is selective to
      Li+ in human plasma even in the presence of a high concentration of Na+ ions.
      This novel sensor concept represents a significant advance in wearable sensor
      technology which will target lithium drug monitoring from under the skin.

PMID- 30095252
TI  - Metal-Free C-5 Hydroxylation of 8-Aminoquinoline Amide.
AB  - Diacetoxyiodobenzene-mediated remote hydroxylation of 8-aminoquinoline amide at
      the C-5 position has been developed. Various aryl, heteroaryl, and aliphatic
      carboxamides work well to afford the hydroxylated derivatives in good yields.
      This protocol is scalable and exhibits high functional group tolerance.
      Experimental results suggest that the reaction likely proceeds through the single
      electron-transfer pathway.

PMID- 30095254
TI  - Neuroanatomical Localization of Galanin in Zebrafish Telencephalon and
      Anticonvulsant Effect of Galanin Overexpression.
AB  - Galanin is a neuropeptide widely expressed in the nervous system, but it is also
      present in non-neuronal locations. In the brain, galanin may function as an
      inhibitory neurotransmitter. Several studies have shown that galanin is involved
      in seizure regulation and can modulate epileptic activity in the brain. The
      overall goal of the study was to establish zebrafish as a model to study the
      antiepileptic effect of galanin. The goal of this study was achieved by (1)
      determining neuroanatomical localization of galanin in zebrafish lateral pallium,
      which is considered to be the zebrafish homologue of the mammalian hippocampus,
      the brain region essential for initiation of seizures, and (2) testing the
      anticonvulsant effect of galanin overexpression. Whole mount immunofluorescence
      staining and pentylenotetrazole (PTZ)-seizure model in larval zebrafish using
      automated analysis of motor function and qPCR were used in the study.
      Immunohistochemical staining of zebrafish larvae revealed numerous galanin-IR
      fibers innervating the subpallium, but only scarce fibers reaching the dorsal
      parts of telencephalon, including lateral pallium. In three-month old zebrafish,
      galanin-IR innervation of the telencephalon was similar; however, many more
      galanin-IR fibers reached the dorsal telencephalon, but in the lateral pallium
      only scarce galanin-IR fibers were visible. qRT-PCR revealed, as expected, a
      strong increase in the expression of galanin in the Tg(hsp70l:galn) line after
      heat shock; however, also without heat shock, the galanin expression was several
      fold higher than in the control animals. Galanin overexpression resulted in
      downregulation of c-fos after PTZ treatment. Behavioral analysis showed that
      galanin overexpression inhibited locomotor activity in PTZ-treated and control
      larvae. The obtained results show that galanin overexpression reduced the
      incidence of seizure-like behavior episodes and their intensity but had no
      significant effect on their duration. The findings indicate that in addition to
      antiepileptic action, galanin modulates arousal behavior and demonstrates a
      sedative effect. The current study showed that galanin overexpression correlated
      with a potent anticonvulsant effect in the zebrafish PTZ-seizure model.

PMID- 30095253
TI  - Energy Transduction in Nitrogenase.
AB  - Nitrogenase is a complicated two-component enzyme system that uses ATP binding
      and hydrolysis energy to achieve one of the most difficult chemical reactions in
      nature, the reduction of N2 to NH3. One component of the Mo-based nitrogenase
      system, Fe protein, delivers electrons one at a time to the second component, the
      catalytic MoFe protein. This process occurs through a series of synchronized
      events collectively called the "Fe protein cycle". Elucidating details of the
      events associated with this cycle has constituted an important challenge in
      understanding the nitrogenase mechanism. Electron delivery is a multistep process
      involving three metal clusters with intra- and interprotein events. It is
      proposed that the first electron transfer event is a gated intraprotein transfer
      of one electron from the MoFe protein P-cluster to the FeMo cofactor. Measurement
      of the effect of osmotic pressure on the rate of this electron transfer process
      revealed that it is gated by protein conformational changes. This first electron
      transfer is activated by binding of the Fe protein containing two bound ATP
      molecules. The mechanism of how this protein-protein association triggers
      electron transfer remains unknown. The second electron transfer event is proposed
      to be a rapid interprotein "backfill" with transfer of one electron from the
      reduced Fe protein 4Fe-4S cluster to the oxidized P-cluster. In this way,
      electron delivery can be viewed as a case of "deficit spending". Such a deficit
      spending electron transfer process can be envisioned as a way to achieve one
      direction electron flow, limiting the potential for back electron flow.
      Hydrolysis of two ATP molecules associated with the Fe protein occurs after the
      electron transfer and therefore is not used to directly drive the electron
      transfer. Rather, ATP hydrolysis is proposed to contribute to relaxation of the
      "activated" conformational state associated with the ATP form of the complex,
      with the free energy from ATP hydrolysis being used to pay back energy associated
      with component protein association and electron transfer. Release of inorganic
      phosphate (Pi) and protein-protein dissociation follow electron transfer and ATP
      hydrolysis. The rate-limiting step for the Fe protein cycle is not dissociation
      of the two proteins, as previously believed, but rather is release of Pi after
      ATP hydrolysis, which is then followed by rapid protein-protein complex
      dissociation. Nitrogenase is composed of two catalytic halves that do not
      function independently but rather exhibit anticooperative nuclear motion in which
      electron transfer in one-half of the complex partially inhibits electron transfer
      and ATP hydrolysis in the other half. Calculations indicated the existence of
      anticooperative interactions across the entire nitrogenase complex, suggesting a
      mechanism for the control of events on opposite ends of this large complex. The
      mechanistic necessity for this anticooperative process remains unknown. This
      Account presents a working model for how all of these processes work together in
      the nitrogenase "machine" to transduce the energy from ATP binding and hydrolysis
      to drive N2 reduction.

PMID- 30095256
TI  - Synthesis, Crystal Structures, and Magnetic and Electrochemical Properties of
      Highly Phenyl Substituted Trinuclear 5,6,11,12,17,18-Hexaazatrinaphthylene
      (HATNPh6)-Bridged Titanium Complexes.
AB  - Trinuclear titanium complexes coordinated by one ligand with three coordination
      sites have shown properties of mixed valency and a high number of reversible
      redox steps. Herein we report on the hexaphenyl-substituted derivative
      (Cp2Ti)3(MU3-HATNPh6) (2). On reaction of 2 with the ferrocenium salt [Cp2Fe]BF4,
      the cationic complexes [(Cp2Ti)3(MU3-HATNPh6)] n+ ( n = 1-3; 3-5) become
      available in a selective way. Cyclic voltammograms show 10 reversible redox
      states of the trinuclear species 2 without decomposition. In order to classify
      the degree of electronic communication between the titanium centers,
      comproportionation constants Kc, IVCT bands in NIR spectra, and magnetic
      measurements were analyzed. These parameters show strong coupling effects between
      the titanium centers but no full delocalization. In addition, single-crystal X
      ray analysis of the neutral complex 2 and its oxidation products (1+ (3), 2+ (4),
      and 3+ (5)) revealed the geometric structure of the molecule in the solid state.
      For the cationic species anion-pi interactions between the electron-deficient
      central ring of the HATNPh6 ligand and BF4- counterions were found.

PMID- 30095255
TI  - Computationally Assisted Design of Polarizing Agents for Dynamic Nuclear
      Polarization Enhanced NMR: The AsymPol Family.
AB  - We introduce a new family of highly efficient polarizing agents for dynamic
      nuclear polarization (DNP)-enhanced nuclear magnetic resonance (NMR)
      applications, composed of asymmetric bis-nitroxides, in which a piperidine-based
      radical and a pyrrolinoxyl or a proxyl radical are linked together. The design of
      the AsymPol family was guided by the use of advanced simulations that allow
      computation of the impact of the radical structure on DNP efficiency. These
      simulations suggested the use of a relatively short linker with the intention to
      generate a sizable intramolecular electron dipolar coupling/ J-exchange
      interaction, while avoiding parallel nitroxide orientations. The characteristics
      of AsymPol were further tuned, for instance with the addition of a conjugated
      carbon-carbon double bond in the 5-membered ring to improve the rigidity and
      provide a favorable relative orientation, the replacement of methyls by
      spirocyclohexanolyl groups to slow the electron spin relaxation, and the
      introduction of phosphate groups to yield highly water-soluble dopants. An in
      depth experimental and theoretical study for two members of the family, AsymPol
      and AsymPolPOK, is presented here. We report substantial sensitivity gains at
      both 9.4 and 18.8 T. The robust efficiency of this new family is further
      demonstrated through high-resolution surface characterization of an important
      industrial catalyst using fast sample spinning at 18.8 T. This work highlights a
      new direction for polarizing agent design and the critical importance of
      computations in this process.

PMID- 30095257
TI  - Dual-Signal Luminescent Detection of Dopamine by a Single Type of Lanthanide
      Doped Nanoparticles.
AB  - Detection of dopamine, an important neurotransmitter, is vital for understanding
      its roles in mammals and disease diagnosis. However, commonly available methods
      for dopamine detection typically rely on a single signal readout, which can be
      susceptible to interference by internal or external factors. Here, we report a
      dual-signal detection of dopamine based on label-free luminescent NaGdF4:Tb
      nanoparticles. In the presence of dopamine, the NaGdF4:Tb nanoparticles exhibit
      luminescence quenching under the excitation of 272 nm, while they give enhanced
      luminescence under 297 nm excitation, realizing both turn off and turn on
      detection of dopamine. The nanoparticle-based dual-signal sensors exhibit high
      sensitivity, with a detection limit of ~30 nM, and good selectivity, which offers
      the possibility to identify potential interferents in the samples. We further
      demonstrate that the dual-signal response results from different energy-transfer
      processes within the nanoparticles under the excitation of different light. The
      new strategy demonstrated here should pave the way for the development of
      multiresponse nanosensors based on lanthanide-doped luminescent nanomaterials.

PMID- 30095258
TI  - Well-Adhering, Easily Producible Photonic Reflective Coatings for Plastic
      Substrates.
AB  - The development of well-adhering, easily producible photonic reflective coatings
      is still a challenge. Here, an easy-to-produce, industrial viable process is
      reported that uses a primer layer of the so-called type II photoinitiator to
      obtain an excellent adhesion between a plastic substrate and one-dimensional (1D)
      photonic liquid crystalline coatings. Furthermore, a good alignment of the
      reactive cholesteric liquid crystal mixture is obtained using a bar-coating
      process, without alignment layers or surfactants. After photopolymerization,
      cross-hatch tape tests show a good adhesion of the photonic coating having a
      reflection band of 50% transmission with almost no scattering. Additionally, we
      demonstrate the ability to create well-adhering ~100% reflective coatings by
      coating double layers and the ability to create single-layered cholesteric
      broadband reflectors using solely a reactivity gradient created by the primer
      layer. Our new interfacial method gives new opportunities to use reflecting 1D
      photonic coatings in industrial processes and applications and allows the bonding
      of almost any polymer to a plastic substrate.

PMID- 30095259
TI  - Characterization of UDP-Glycosyltransferase Involved in Biosynthesis of
      Ginsenosides Rg1 and Rb1 and Identification of Critical Conserved Amino Acid
      Residues for Its Function.
AB  - Ginsenosides attract great attention for their bioactivities. However, their
      contents are low, and many UDP-glycosyltransferases (UGTs) that play crucial
      roles in the ginsenoside biosynthesis pathways have not been identified, which
      hinders the biosynthesis of ginsenosides. In this study, we reported that one UDP
      glycosyltransferase, UGTPg71A29, from Panax ginseng could glycosylate C20-OH of
      Rh1 and transfer a glucose moiety to Rd, producing ginsenosides Rg1 and Rb1,
      respectively. Ectopic expression of UGTPg71A29 in Saccharomyces cerevisiae stably
      generated Rg1 and Rb1 under its corresponding substrate. Overexpression of
      UGTPg71A29 in transgenic cells of P. ginseng could significantly enhance the
      accumulation of Rg1 and Rb1, with their contents of 3.2- and 3.5-fold higher than
      those in the control, respectively. Homology modeling, molecular dynamics, and
      mutational analysis revealed the key catalytic site, Gln283, which provided
      insights into the catalytic mechanism of UGTPg71A29. These results not only
      provide an efficient enzymatic tool for the synthesis of glycosides but also help
      achieve large-scale industrial production of glycosides.

PMID- 30095260
TI  - Isotopic Effects on Intermolecular and Intramolecular Structure and Dynamics in
      Hydrogen, Deuterium, and Tritium Liquids: Normal Liquid and Weakly and Strongly
      Cooled Liquids.
AB  - Differences in properties such as phase-transition temperature and transport
      coefficients among liquids of different isotopic compositions, hydrogen,
      deuterium, and tritium, should originate from their differently pronounced
      nuclear quantum effects (NQEs) rather than from any subtle difference in the
      electronic interaction potentials. Accurate and efficient determination of
      structural and dynamical isotopic effects in the quantum liquids still remains as
      one of the challenging problems in condensed-phase physics. With a recently
      developed nonempirical real-time molecular dynamics method which describes
      nonspherical molecules with the NQEs, we computationally realized and
      investigated dynamical and quantum isotopic effects of not only traditionally
      studied isotopes, hydrogen, and deuterium but also a lesser known radioisotope,
      tritium, in broad thermodynamic conditions from normal liquid to weakly and
      strongly cooled liquids, which have been hindered by rapid crystallization in
      spite of numerous experimental attempts at supercooling. Reproducing the
      previously reported experimental isotope dependence on the bond length and
      vibrational frequencies of hydrogen, deuterium, and tritium liquids, we further
      demonstrate that distinctive isotope effects appear in their intermolecular and
      intramolecular structure and dynamics not only at lower temperature but also at
      higher temperature, which none has so far been able to obtain quantitative
      results for realistic systems. Rationalization of their physical origins and the
      obtained physical insights will help future experimental searching and monitoring
      intermolecular and intramolecular dynamics and structures of these isotopes not
      only in normal liquid but also in supercooled liquid.

PMID- 30095261
TI  - Rhabdopeptide/Xenortide-like Peptides from Xenorhabdus innexi with Terminal
      Amines Showing Potent Antiprotozoal Activity.
AB  - Seven new rhabdopeptide/xenortide-like peptides (RXPs) (1-7) with putrescine or
      ammonia as the C-terminal amines were isolated from Xenorhabdus innexi DSM 16336.
      Their chemical structures were elucidated by high-resoultion mass spectroscopy
      (HR-MS) and one-dimensional (1D) and two-dimensional (2D) NMR. They were
      evaluated for their activities against protozoan parasites and cytotoxicity
      against rat skeletal myoblasts (L6 cells). All tested compounds exhibited strong
      effects against Trypanosoma brucei rhodesiense and Plasmodium falciparum, with
      IC50 values of 0.07-6.25 and 0.091-3.16 MUM, respectively, making them the most
      active RXP derivatives known to date.

PMID- 30095262
TI  - Blending Mechanism of PS- b-PEO and PS Homopolymer at the Air/Water Interface and
      Their Morphological Control.
AB  - We report a blending mechanism of polystyrene- b-poly(ethylene oxide) (PS- b-PEO)
      and PS homopolymer (homoPS) at the air/water interface. Our blending mechanism is
      completely different from the well-known "wet-dry brush theory" for bulk blends;
      regardless of the size of homoPS, the domain size increased and the morphology
      changed without macrophase separation, whereas the homoPS of small molecular
      weight (MW) leads to a transition after blending into the block copolymer
      domains, and the large MW homoPS is phase-separated in bulk. The difference in
      blending mechanism at the interface is attributed to adsorption kinetics at a
      water/spreading solvent interface. Upon spreading, PS- b-PEO is rapidly adsorbed
      to the water/spreading solvent interface and forms domain first, and then homoPS
      accumulates on them as the solvent completely evaporates. On the basis of our
      proposed mechanism, we demonstrate that rapid PS- b-PEO adsorption is crucial to
      determine the final morphology of the blends. We additionally found that
      spreading preformed self-assemblies of the blends slowed down the adsorption,
      causing them to behave similar to bulk blends, following the "wet-dry brush
      theory". This new mechanism provides useful information for various block
      copolymer-homopolymer blending systems with large fluid/fluid interfaces such as
      emulsions and foams.

PMID- 30095263
TI  - Copper-Catalyzed Double C(sp3)-Si Coupling of Geminal Dibromides: Ionic-to
      Radical Switch in the Reaction Mechanism.
AB  - A method for converting geminal dibromides into 1,1-disilylated alkanes is
      reported. The reaction is promoted by a copper(I) catalyst generated in situ from
      CuBr.SMe2 as a precatalyst and 4,4'-di- tert-butyl-2,2'-bipyridine (dtbpy) as a
      ligand. A Si-B reagent is used as the silicon pronucleophile. It is shown that
      the two C(sp3)-Si bond-forming events differ in mechanism, with the first being
      ionic and the second being radical.

PMID- 30095264
TI  - Kinetic Schemes in Open Interacting Systems.
AB  - We discuss utilization of kinetic schemes for description of open interacting
      systems, focusing on vibrational energy relaxation for an oscillator coupled to a
      nonequilibirum electronic bath. Standard kinetic equations with constant rate
      coefficients are obtained under the assumption of time scale separation between
      the system and bath, with the bath dynamics much faster than that of the system
      of interest. This assumption may break down in certain limits, and we show that
      ignoring this may lead to qualitatively wrong predictions. Connection with more
      general, nonequilibrium Green's function (NEGF) analysis is demonstrated. Our
      considerations are illustrated within generic molecular junction models with
      electron-vibration coupling.

PMID- 30095265
TI  - Rational Design of Two-dimensional Anode Materials: B2S as a Strained Graphene.
AB  - Alkali metal atom adsorption energy is an important descriptor for anode material
      design. In this study, an energy decomposition model is developed to provide
      valuable insights in understanding how the adsorption behavior can be tuned. As
      an example, Li adsorption on graphene enhanced by a tensile strain is analyzed
      based on this model. Such an analysis then motivates us to find a system with
      similar electronic structure but larger lattice parameter compared to graphene as
      an anode material. Our first-principles calculations indicate that B2S, as an
      isoelectronic system of graphene, is a good candidate. Its capacity is as high as
      1498 mA h g-1 for both Li and Na ion batteries. Li and Na diffusion barriers on
      B2S are 0.45 and 0.23 eV, respectively. This study opens a new avenue for
      adsorption-behavior-guided two-dimensional material design.

PMID- 30095266
TI  - Intramolecular Vibrations Complement the Robustness of Primary Charge Separation
      in a Dimer Model of the Photosystem II Reaction Center.
AB  - The energy conversion of oxygenic photosynthesis is triggered by primary charge
      separation in proteins at the photosystem II reaction center. Here, we
      investigate the impacts of the protein environment and intramolecular vibrations
      on primary charge separation at the photosystem II reaction center. This is
      accomplished by combining the quantum dynamic theories of condensed phase
      electron transfer with quantum chemical calculations to evaluate the vibrational
      Huang-Rhys factors of chlorophyll and pheophytin molecules. We report that
      individual vibrational modes play a minor role in promoting charge separation,
      contrary to the discussion in recent publications. Nevertheless, these small
      contributions accumulate to considerably influence the charge separation rate,
      resulting in subpicosecond charge separation almost independent of the driving
      force and temperature. We suggest that the intramolecular vibrations complement
      the robustness of the charge separation in the photosystem II reaction center
      against the inherently large static disorder of the involved electronic energies.

PMID- 30095267
TI  - Multivalent Presentation of Ice Recrystallization Inhibiting Polymers on
      Nanoparticles Retains Activity.
AB  - Poly(vinyl alcohol) (PVA) has emerged as the most potent mimic of antifreeze
      (glyco)proteins ice recrystallization inhibition (IRI) activity, despite its lack
      of structural similarities and flexible, rather than rigid, backbone. The precise
      spacing of hydroxyl groups is hypothesized to enable PVA to recognize the prism
      planes of ice but not the basal plane, due to hydroxyl pattern matching of the
      ice surface giving rise to the macroscopic activity. Here, well-defined PVA
      derived from reversible addition-fragmentation chain-transfer (RAFT)
      polymerization is immobilized onto gold nanoparticles to enable the impact of
      nanoscale assembly and confinement on the observed IRI activity. Unlike previous
      reports using star-branched or bottle-brush PVAs, the nanoparticle-PVA retains
      all IRI activity compared to polymers in solution. Evidence is presented to show
      that this is due to the low grafting densities on the particle surface meaning
      the chains are free to explore the ice faces, rather than being constrained as in
      star-branched polymers. These results demonstrate a route to develop more
      functional IRI's and inclusion of metallic particle cores for imaging and
      associated applications in cryobiology.

PMID- 30095268
TI  - Unravelling the Effects of A-Site Cations on Nonradiative Electron-Hole
      Recombination in Lead Bromide Perovskites: Time-Domain ab Initio Analysis.
AB  - Lead bromide perovskites APbBr3 (A = Cs, MA, FA) hold great promise in
      optoelectronics and photovoltaics. Because the band gaps of the three materials
      are similar, and also because the A-site cation does not contribute to band
      edges, one would expect a minor influence of A-site cation on the excited-state
      lifetime of the perovskites. Experiments defy that expectation. By performing ab
      initio nonadiabatic (NA) molecular dynamics combined with time-domain density
      functional simulations, we demonstrate that the nonradiative electron-hole
      recombination times are in the order FAPbBr3 > MAPbBr3 > CsPbBr3, which are
      determined by the NA electron-phonon coupling because decoherence times are
      similar. The simulations show that the larger A-site cation and the smaller NA
      coupling because larger A-site cation suppresses the Pb-Br cages' motion. The
      electron-hole recombination is slow, ranging from subnanosecond to nanoseconds,
      because the NA coupling is small, less than 3 meV, and because decoherence time
      is slow, less than 7 fs. Both the trend of recombination and the time scales show
      excellent agreement with experiments. The time-domain atomistic simulations
      rationalize the experimental observations and advance our understanding of the
      cations' influence on perovskite excited-state lifetimes.

PMID- 30095269
TI  - Domino Reaction Sequence for the Synthesis of [2.2.2]Diazabicycloalkenes and Base
      Promoted Cycloreversion to 2-Pyridone Alkaloids.
AB  - A new domino reaction sequence for the construction of 2-pyridone structures is
      reported. The reaction sequence begins with diacetyldiketopiperazine and proceeds
      via aldol condensation, alkene isomerization, and intramolecular Diels-Alder
      cycloaddition. The intermediate [2.2.2]diazabicycloalkene cycloadducts can be
      isolated or can engage in a base-accelerated extrusion of one lactam bridge to
      provide the 2-pyridone cycloreversion products. The operation leading to pyridone
      products can occur in one reaction vessel and proceeds at convenient
      temperatures.

PMID- 30095270
TI  - Fusicoccane-Derived Diterpenoids from Alternaria brassicicola: Investigation of
      the Structure-Stability Relationship and Discovery of an IKKbeta Inhibitor.
AB  - The structure-stability relationships of 1-6 were investigated to show that 1
      converted to 5 via a kinetic, solution-mediated autoxidation. In addition,
      alterbrassicene A (7), a fusicoccane-derived diterpenoid bearing an unprecedented
      5/9/4-fused carbocyclic skeleton with a rare fused 2-cyclobuten-1-one motif, was
      characterized from Alternaria brassicicola. Its absolute structure was elucidated
      by spectroscopic analyses and quantum chemical calculations. Compound 7 was the
      first fusicoccane derivative acting as a potent IKKbeta inhibitor in the NF
      kappaB signaling pathway.

PMID- 30095271
TI  - Supramolecular Hybrid Structures and Gels from Host-Guest Interactions between
      alpha-Cyclodextrin and PEGylated Organosilica Nanoparticles.
AB  - Polypseudorotaxanes are polymer chains threaded by molecular rings that are free
      to unthread; these "pearl-necklace" can self-assemble further, leading to higher
      order supramolecular structures with interesting functionalities. In this work,
      the complexation between alpha-cyclodextrin (alpha-CD), a cyclic oligosaccharide
      of glucopyranose units, and poly(ethylene glycol) (PEG) grafted to silica
      nanoparticles was studied. The threading of alpha-CD onto the polymeric chains
      leads to their aggregation into bundles, followed by either the precipitation of
      the inclusion complex or the formation of a gel phase, in which silica
      nanoparticles are incorporated. The kinetics of threading, followed by
      turbidimetry, revealed a dependence of the rate of complexation on the following
      parameters: the concentration of alpha-CD, temperature, PEG length (750, 4000,
      and 5000 g mol-1), whether the polymer is grafted or free in solution, and the
      density of grafting. Complexation is slower, and temperature has a higher impact
      on PEG grafted on silica nanoparticles compared to PEG free in solution.
      Thermodynamic parameters extracted from the transition-state theory showed that
      inclusion complex formation is favored with grafted PEG compared to free PEG and
      establishes a ratio of complexation of five to six ethylene oxide units per
      cyclodextrin. The complexation yields, determined by gravimetry, revealed that
      much higher yields are obtained with longer chains and higher grafting density.
      Thermogravimetric analysis and Fourier transform infrared spectroscopy on the
      inclusion complex corroborate the number of macrocycles threaded on the chains. A
      sol-gel transition was observed with the longer PEG chain (5k) at specific mixing
      ratios; oscillatory shear rheology measurements confirmed a highly solid-like
      behavior, with an elastic modulus G' of up to 25 kPa, higher than that in the
      absence of silica. These results thus provide the key parameters dictating
      inclusion complex formation between cyclodextrin and PEG covalently attached to
      colloidal silica and demonstrate a facile route toward soft nanoparticle gels
      based on host-guest interactions.

PMID- 30095272
TI  - Inclusion of Phase-Change Materials in Submicron Silica Capsules Using a
      Surfactant-Free Emulsion Approach.
AB  - Microencapsulation of phase-change materials is of great importance for thermal
      energy-storage applications. In this work, we report on a facile approach to
      enclose paraffin in mechanically strong submicron silica capsules without the
      addition of any classical organic surfactants. A liquid silica precursor polymer,
      hyperbranched polyethoxysiloxane (PEOS), is used as both silica source and
      stabilizer of oil-in-water emulsions because of its hydrolysis-induced
      interfacial activity. Hydrophobic paraffin is microencapsulated in silica with
      quantitative efficiency simply by emulsifying the mixture of molten paraffin and
      PEOS in water under ultrasonication or high-shear homogenization. The size of the
      capsules can be controlled by emulsification energy and rate of subsequent
      stirring. The silica shell, whose thickness can be easily tuned by varying the
      paraffin to PEOS ratio, acts as an effective barrier layer retarding
      significantly the evaporation of enclosed substances; meanwhile, the
      microencapsulated paraffin maintains the excellent phase-change performance. This
      technique offers a low-cost, highly scalable, and environmentally friendly
      process for microencapsulation of paraffin phase-change materials.

PMID- 30095273
TI  - Enantioselective Reaction between 2-(Cyanomethyl)azaarenes and N-Boc-amino
      Sulfones.
AB  - A series of 2-(cyanomethyl)azaarenes containing benzothiazole or benzoxazole were
      designed and synthesized for asymmetric alpha-functionalization with N-Boc-amino
      sulfones. The Mannich adducts were obtained in high yields with good diastereo-
      and enantioselectivities. Aryl-substituted amino sulfones were tolerated under
      the current conditions, and the reaction can be performed on gram scale in good
      results.

PMID- 30095274
TI  - Infrared Spectroscopic Quantification of Methacrylation of Hyaluronic Acid: A
      Scaffold for Tissue Engineering Applications.
AB  - Methacrylated hyaluronic acid (MeHA) has been used extensively in tissue
      engineering and drug delivery applications. The degree of methacrylation (DM) of
      HA impacts hydrogel crosslinking, which is of pivotal importance for cell
      interactions. The methacrylation reaction occurs over several hours, and DM is
      currently assessed post reaction and after dialysis of the solution, using
      nuclear magnetic resonance (1H NMR) data. Thus, there is little control over
      exact DM in a specific reaction. Here, infrared (IR) spectroscopy in attenuated
      total reflection (ATR) mode was investigated as an alternate modality for
      assessment of the DM of HA hydrogels, including during the reaction progression.
      Attenuated total reflection is a low-cost technique that is widely available in
      research and industry labs that can be used online during the reaction process.
      Strong correlations were achieved with IR-derived peak heights from dialyzed and
      lyophilized samples at 1708 cm-1 (from the methacrylic ester carbonyl vibration),
      and 1H NMR values ( R = 0.92, P = 6.56E-11). Additional IR peaks of importance
      were identified using principal component analysis and resulted in significant
      correlations with the 1H NMR DM parameter: 1454 cm-1 ( R = 0.85, P = 2.81E-8),
      1300 cm-1 ( R = 0.95, P = 4.50E-14), 950 ( R = 0.85, P = 3.55E-8), 856 cm-1 ( R =
      0.94, P = 1.20E-12), and 809 cm-1 ( R = 0.93, P = 3.54E-12). A multiple linear
      regression model to predict 1H NMR-derived DM using the 1708, 1300, and 1200 cm-1
      peak heights as independent variables resulted in prediction with an error of
      3.2% using dialyzed and lyophilized samples ( P < 0.001). Additionally, a
      multilinear regression model to predict the DM in undialyzed liquid MeHA samples
      obtained during the reaction process using similar peak height positions as
      independent variables resulted in a prediction error of 0.81% ( P < 0.05). Thus,
      IR spectroscopy can be utilized as an alternate modality to 1H NMR for
      quantification of the DM of MeHA while sampling either on-line during the
      methacrylation reaction as well as in post-lyophilized products. This could
      greatly simplify workflow for tissue engineering and other applications.

PMID- 30095275
TI  - Response to "Managing autism spectrum disorder in developing countries by
      utilizing existing resources: A perspective from Bangladesh".

PMID- 30095276
TI  - Status of Legislative Efforts to Promote and Protect Breastfeeding and the
      Provision of Human Milk for Women Returning to Work in the First Postpartum Year.
AB  - INTRODUCTION: Women account for over 50% of the workforce in the United States
      with many working women being of childbearing age. The United States does not
      provide long paid parental leave, thus mothers who choose to breastfeed are
      confronted with the reality of combining breastfeeding and returning to work.
      Return to work is reported to negatively impact breastfeeding exclusivity and
      duration. While the existing federal law protects some women, not all women have
      legal support to breastfeed or express milk at work. Exemptions to the federal
      law include limitations related to the employee's status, classification of
      employer, total number of employees and the employer's annual revenue. This study
      aimed to examine existing city-level legislation protecting the rights of women
      to breastfeed or express milk at their place of employment during the postpartum
      period. MATERIALS AND METHODS: Prospective descriptive study with survey. The
      national sample includes the three largest cities of each state and the capital
      city of the United States (Washington, DC) for a total of 151 cities. The data
      were collected in a tiered approach with three phases: (1) assessment of city
      website, (2) e-mail to city mayor's office, and (3) telephone follow-up with the
      city's office. RESULTS: Only 2/151 (1.3%) of cities had specific legislation
      outlining the protections for all breastfeeding women in the workplace.
      CONCLUSIONS: This research demonstrates a clear need for political action to
      increase the number of women who have workplace regulations to protect
      breastfeeding.

PMID- 30095277
TI  - Making the future together: Shaping autism research through meaningful
      participation.
AB  - Participatory research methods connect researchers with relevant communities to
      achieve shared goals. These methods can deliver results that are relevant to
      people's lives and thus likely to have a positive impact. In the context of a
      large and growing body of autism research, with continued poor implementation,
      and some evidence of community dissatisfaction, there is a powerful case for
      participatory autism research. In order to develop a framework for such
      collaborative working, a UK seminar series was organised and co-produced by
      autistic and non-autistic people with academic, practitioner and lived expertise.
      This article reports on the outcomes from the series, identifying five topics
      relevant to building a community of practice in participatory research: Respect,
      Authenticity, Assumptions, Infrastructure and Empathy. Each topic is connected to
      a specific example from within and beyond research, to inspire new practices in
      the field. We call for the development of participatory research skills among the
      autism research community and the facilitation of greater autistic leadership of,
      and partnership in, research. Such work, if delivered to a high standard, is
      likely to lead to better translation into practice and improved outcomes for
      autistic people and those who support them.

PMID- 30095278
TI  - Impact of socioeconomic status on coronary artery calcification.
AB  - Background Low socioeconomic status is associated with an increased risk of
      coronary artery disease, but few studies have investigated the potential link
      between living in an area with a low versus a high socioeconomic status and
      coronary artery calcification, a marker of subclinical coronary artery disease.
      Design The design of this study was a cross-sectional study. Methods We evaluated
      1067 participants with no history of coronary artery disease from the pilot phase
      of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Men and women aged 50-64
      years were recruited from three high-socioeconomic status ( n = 541) and three
      low-socioeconomic status ( n = 526) areas in the city of Gothenburg (550,000
      inhabitants). The coronary artery calcification score was assessed with the
      Agatston method using computed tomography, with individuals classified into
      either no coronary calcification ( n = 625; mean age, 57 years) or any coronary
      artery calcification ( n = 442; mean age, 59 years (men, 68.5%)). Results
      Coronary artery calcification was present in 244 (46.3%) and 198 (36.6%)
      individuals from the low- and high-socioeconomic status areas, respectively.
      Participants from the low-socioeconomic status areas had a significantly higher
      risk factor burden. In a multivariable logistic regression model with adjustment
      for age, sex and cardiovascular risk factors, the odds for coronary artery
      calcification were not significantly higher among persons living in low
      socioeconomic status areas (odds ratio = 1.18, 95% confidence interval = 0.87
      1.60). Conclusion In this relatively small cross-sectional study, we observed an
      association between living in a low-socioeconomic status area and coronary artery
      calcification. However, this was mostly explained by higher levels of
      cardiovascular disease risk factors, indicating that the effect of socioeconomic
      status on the atherosclerotic process works through an increased burden of
      cardiovascular disease risk factors.

PMID- 30095279
TI  - Childbirth as a forthcoming traumatic event: pretraumatic stress disorder during
      pregnancy and its psychological correlates.
AB  - BACKGROUND: Recent research has suggested that pretraumatic stress related to a
      forthcoming predictable traumatic event might exist and that such stress
      reactions would be a key, 'but largely ignored', aspect of the etiology of
      Posttraumatic Stress Disorder (PTSD). While it is now acknowledged that
      childbirth may lead to PTSD, less is known regarding pretraumatic reactions in
      pregnancy. This study aims to (a) explore the frequency of PTSD, Fear of
      Childbirth and tokophobia associated with the forthcoming delivery and (b)
      highlight associated features of pre-traumatic stress symptoms. METHODS: At 34
      weeks' gestation, a sample of 102 women completed questionnaires assessing
      anticipated labour pain, fear of childbirth, fear of pain, pretraumatic stress
      symptoms, perceived social support and depressive and anxiety symptoms. RESULTS:
      8.8% of women met DSM-IV-TR criteria for PTSD related to the threatening
      forthcoming delivery. Fear of childbirth, anticipated labour pain, anxiety, and
      depressive symptoms were significant predictors of pretraumatic stress intensity.
      CONCLUSION: Our results extend prior findings on postpartum PTSD by showing that
      fear of labour pain is a specific construct, clearly independent from the
      experience of general pain. Our results suggest that childbirth may be
      experienced as threatening and traumatic and that this traumatic impact might
      develop way before the delivery. As a potential traumatic continuum from pre- to
      posttraumatic stress might exist, further longitudinal studies assessing pre-,
      peri- and posttraumatic reactions is needed to provide support for this
      hypothesis.

PMID- 30095280
TI  - Can't take the heat: sauna and Fentanyl patch intoxication.

PMID- 30095282
TI  - The homeostatic feeding response to fasting is under chronostatic control.
AB  - Eating behavior is controlled by the energy needs of the organism. The need to
      provide a constant supply of energy to tissues is a homeostatic drive that
      adjusts feeding behavior to the energetic condition of the organism. On the other
      hand, food intake also shows a circadian variation synchronized to the light-dark
      cycle and food availability. Thus, feeding is subjected to both homeostatic and
      circadian regulation mechanisms that determine the amount and timing of
      spontaneous food intake in normal conditions. In the present study we contrasted
      the influence of the homeostatic versus the chronostatic mechanisms on food
      intake in normal conditions and in response to fasting. A group of rats was
      subjected to food deprivation under two different temporal schemes. A constant
      length 24-h food deprivation started at different times of day resulted in an
      increased compensatory intake. This compensatory response showed a circadian
      variation that resembled the rhythm of intake in non-deprived animals. When
      subjected to fasting periods of increasing length (24-66 h), the amount of
      compensatory feeding varied according to the time of day in which food was made
      available, being significantly less when the fast ended in the middle of the
      light phase or beginning of the dark phase. These oscillatory changes did not
      have a correlation with variations in the level of glucose or beta
      hydroxybutyrate in the blood. The results suggest that the mechanism of
      homeostatic compensation is modulated chronostatically, presumably as part of the
      alternation of catabolic and anabolic states matching the daily cycles of
      activity.

PMID- 30095281
TI  - Percutaneous Computed Tomography-Guided Lung Biopsies using a Virtual Navigation
      Guidance: Our Experience.
AB  - OBJECTIVE: To evaluate the effectiveness of a virtual CT-guided navigation system
      (Sirio-MASMEC Biomed) in performing lung biopsies, with greater attention to
      lesions smaller than 1 cm, compared to the traditional procedure. METHODS: This
      study was approved by the Ethics Committee of our Institute. Two hundred patients
      were prospectively selected. Of these, 100 were subjected to percutaneous
      procedure with the use of Sirio and 100 to traditional CT-guided percutaneous
      procedure. The two methods were compared in terms of absorbed dose, procedure
      time, complications, and number of non-diagnostic specimens (diagnostic success).
      RESULTS: Sirio has shown a significant reduction in the absorbed dose and
      procedure times (p < 0.05), with a lower incidence of complications compared to
      the traditional procedure. Sirio has also allowed to carry out biopsies of
      lesions' diameter <=10 mm, obtaining fewer non diagnostic specimens thus
      resulting more effective in terms of diagnostic success. CONCLUSIONS: The use of
      Sirio in sampling biopsy showed a statistically significant reduction in terms of
      performed scans and procedural time with lower incidence of post-procedural
      complications compared to the traditional percutaneous procedure, especially for
      lesions <=10 mm. The best diagnostic result, the reduction of the dose absorbed
      and procedural complications makes the procedures more reliable, safety and less
      invasive. In addition, the reduction of execution time will increase the number
      of daily interventional procedures improving clinical management.

PMID- 30095283
TI  - Myricetin attenuates LPS-induced inflammation in RAW 264.7 macrophages and mouse
      models.
AB  - AIM: Acute lung injury is a common clinical syndrome associated with significant
      morbidity. Myricetin has been demonstrated to inhibit inflammation in a variety
      of diseases. In this study, we aimed to investigate the protective effects of
      myricetin on inflammation in lipopolysaccharide-stimulated RAW 264.7 cells and
      lipopolysaccharide-induced lung injury model. Results/methodology: In this study,
      we detected the anti-inflammatory effects of myricetin by ELISA, RT-PCR and
      Western blot, respectively. Myricetin significantly inhibited the production of
      the proinflammatory cytokines in vitro and in vivo. It exerted an anti
      inflammatory effect through suppressing the NF-kappaB p65 and AKT activation in
      NF-kappaB pathway and JNK, p-ERK and p38 in MAPK signaling pathway. CONCLUSION:
      Myricetin alleviated acute lung injury by inhibiting macrophage activation, and
      inhibited inflammation in vitro and in vivo. It may be a potential therapeutic
      candidate for the prevention of inflammatory diseases.

PMID- 30095284
TI  - Economic analysis of inadequate symptom control in carcinoid syndrome in the
      United States.
AB  - AIM: We investigated the healthcare resource utilization and costs of patients
      with dose escalations beyond recommended levels of long-acting octreotide for
      persistent carcinoid syndrome (CS) symptoms. MATERIALS & METHODS: A retrospective
      study of US health insurance claims included 358 adults with >=1 medical claim
      for CS and >=6 claims for long-acting octreotide (10-30 mg) between 1 July 2006
      and 31 December 2013. RESULTS: Pre-escalation per-patient per-month outcomes and
      costs were lower versus post-escalation, including vascular conditions (0.11 vs
      0.21), metastasis/secondary neoplasms (0.45 vs 0.74), total all-cause costs
      (US$4116 vs US$8305; p < 0.001) and CS-related costs (US$3156 vs US$7101; p <
      0.001). CONCLUSION: Higher mean pre-escalation per-patient per-month resource use
      and costs post-escalation primarily attributable to CS-related ambulatory care
      suggests continuing challenges in managing CS despite octreotide dose escalation.

PMID- 30095285
TI  - Assessment of Risk Factors for Iron Deficiency Anemia in Infants and Young
      Children: A Case-Control Study.
AB  - INTRODUCTION: Iron deficiency anemia (IDA) is common in children aged 0-35 months
      in Lithuania. Nevertheless, there are no studies investigating IDA in this age
      group. We aimed to identify the major risk factors for disease development
      focusing on medical history and dietary habits. METHODS: A prospective case
      control study was conducted in a university hospital. The enrolled cohort was
      divided into three groups: IDA infants (IDA-In; n = 36, aged 3-11 months), IDA
      children (IDA-Ch; n = 23, aged 12-32 months), and healthy controls (HCs; n = 32,
      aged 6-34 months). RESULTS: There was a higher number of premature, low birth
      weight (LBW), and faster gaining weight infants in the IDA-In group. Their diet
      diversity was lower than IDA-Ch and HC. In contrast, the IDA-Ch group had no
      signs of impaired iron stores at birth or higher iron need for fast growth; their
      diet diversity was similar to that of HC, but meat was introduced later as
      compared with those in the IDA-In and HC groups. Consumption of cow's milk was
      rather low among all study participants, but consumption of sugar-added products
      was found to be a new emerging problem. Exclusive breastfeeding did not differ in
      duration and prevalence; the age for introduction of complementary foods was
      similar in all groups. CONCLUSIONS: Low compliance with World Health Organization
      (WHO) recommendations on breastfeeding and complementary feeding suggests an
      urgent need for nutritional counseling in early childhood, especially in
      premature, LBW, and fast gaining weight infants.

PMID- 30095286
TI  - How Communicating Misleading Information Dilutes Public Understanding of Weight
      Loss Mechanisms.
AB  - The biomedical literature describes clearly the direct mechanisms influencing
      weight gain, but broader public discourse on the subject is rife with misleading
      claims about the factors that cause people to gain or lose weight. We examine how
      such misleading claims can dilute accurate information to the point that people
      arrive at poor judgments about the direct causes of weight gain. We adapt the
      conventional experimental paradigm used in dilution research (Nisbett, Zukier, &
      Lemley, 1981) to measure the effect of different information levels of dilution.
      We use a pair of online survey experiments to distinguish the effects of
      receiving distractingly plausible information versus raw information overload.
      These experiments also probe the limits of the dilution effect by using a large
      national sample of participants who vary by their health information efficacy and
      other potential moderators. Results suggest that public confusion about weight
      loss may stem from a dilution effect, which remains constant across a wide range
      of subgroups one might otherwise expect to resist it.

PMID- 30095287
TI  - Age and burnout syndrome in nursing professionals: moderating role of emotion
      focused coping.
AB  - This study examined whether the association between age and the three burnout
      dimensions (emotional exhaustion, depersonalisation and reduced personal
      accomplishment) depend on the extent of nursing professionals' use of emotion
      focused coping strategy. Participants were 283 nurses (Mage = 35 years, SD =
      8.17, Range = 23-66 years) from a tertiary healthcare institution in south
      eastern Nigeria. They completed self-report measures of relevant variables in
      paper and pencil form. Increased age was associated with reduced personal
      accomplishment for nurses with high emotion-focused coping, but not for those who
      were low or moderate in use of emotion-focused coping. Such moderation effects
      were not found for emotional exhaustion and depersonalisation. Findings clarify
      the conditions under which age may be associated with reduced sense of
      achievement at work among nursing professionals. The study adds to knowledge in
      combating burnout in nursing and could guide health managers in developing
      strategies that might prevent or ameliorate nurses' burnout.

PMID- 30095288
TI  - Breastfeeding Experiences of Mothers of Children with Down Syndrome.
AB  - Children with Down syndrome are less likely to be breastfed than typically
      developing children, and breastfeeding has a lower duration compared to
      recommendations of the World Health Organization. The aim of this study was to
      understand the breastfeeding experiences of mothers of children with Down
      syndrome, including their perceptions of the breastfeeding process and their
      specific practices. This is a qualitative study with 10 participants, mothers of
      children aged between 2 months and 9 years. Snowball sampling was used for
      participants' selection, and semi-structured interviews conducted in
      participants' households. Three categories emerged: "the breastfeeding
      experience," involving the process of breastfeeding, the breast milk, feelings,
      and difficulties of this practice; "experiences of health care," encompassing the
      support received by health professionals, dissatisfaction with health services,
      lack of support in breastfeeding, and discontent with health professional
      behavior; and "learning about Down syndrome," with search for information by
      parents and advice to health professionals. In this study, we found evidence that
      breastfeeding success relies very much on mothers' willingness and support of
      health professionals, namely, nurses. Findings from this study suggest that
      support of a multidisciplinary team is essential to the success of breastfeeding.
      Greater awareness is needed regarding the unique rewards and challenges of
      breastfeeding these infants, as well as how families cope with the ongoing
      challenges. Therefore, this research is relevant to understand the experiences of
      mothers of children with DS about breastfeeding, identifying the inhibiting
      factors, in order to create more appropriate strategies to intervene and
      implement practices that contribute to the support and promotion of
      breastfeeding. Results will also influence the education of health professionals,
      emphasizing the importance of multidisciplinary teams for a comprehensive care
      and contributing to increasing evidence available about this topic.

PMID- 30095289
TI  - Randomized comparison of the Baska FESS mask and the LMA Supreme in different
      head and neck positions.
AB  - BACKGROUND: The Baska functional endoscopic sinus surgery (FESS) mask is a new
      supraglottic airway designed for head and neck procedures. This prospective,
      randomized controlled trial compared the oropharyngeal leak pressure (OLP) of the
      Baska FESS mask with the laryngeal mask airway (LMA) Supreme in different head
      and neck positions. METHODS: One hundred patients undergoing elective surgery
      were recruited. OLP was compared in supine position, 45 degrees  lateral
      rotation, 45 degrees  neck extension, and 30 degrees  neck flexion. Glottic view,
      insertion time, ease of insertion, number of attempts, ease and time of insertion
      of gastric tube, and complications were also compared. RESULTS: The OLP of the
      Baska FESS was higher than the LMA Supreme in all head and neck positions studied
      (p < 0.001). Glottic views were better in the Baska FESS in supine and lateral
      rotation. LMA Supreme was easier (p = 0.046) and faster (p < 0.001) to insert.
      First attempt insertion success rates were 91.8% for Baska FESS and 98% for LMA
      Supreme. Gastric drain was easier and faster to insert (p < 0.001) in the LMA
      Supreme. CONCLUSIONS: The Baska FESS provides a superior airway seal with higher
      mean OLP than the LMA Supreme in all head and neck positions studied. However,
      LMA Supreme was superior in terms of ease and speed of insertion.

PMID- 30095291
TI  - Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids.
AB  - Microbial nucleic acids are major signatures of invading pathogens, and their
      recognition by various host pattern recognition receptors (PRRs) represents the
      first step toward an efficient innate immune response to clear the pathogens. The
      nucleic acid-sensing PRRs are localized at the plasma membrane, the cytosol,
      and/or various cellular organelles. Sensing of nucleic acids and signaling by
      PRRs involve recruitment of distinct signaling components, and PRRs are
      intensively regulated by cellular organelle trafficking. PRR-mediated innate
      immune responses are also heavily regulated by posttranslational modifications,
      including phosphorylation, polyubiquitination, sumoylation, and glutamylation. In
      this review, we focus on our current understanding of recognition of microbial
      nucleic acid by PRRs, particularly on their regulation by organelle trafficking
      and posttranslational modifications. We also discuss how sensing of self nucleic
      acids and dysregulation of PRR-mediated signaling lead to serious human diseases.

PMID- 30095290
TI  - Severe Treatment-Related Lymphopenia in Patients with Newly Diagnosed Rectal
      Cancer.
AB  - BACKGROUND: Although treatment-related lymphopenia (TRL) is common in many
      cancers no data exists in rectal cancer. METHODS: Serial lymphocyte counts were
      analyzed retrospectively in patients with newly diagnosed rectal cancer, serial
      blood counts, and complete records at Johns Hopkins Hospital. RESULTS: Fifty
      seven patients with normal pretreatment lymphocyte counts were studied. Two
      months after beginning chemoradiation, 35% of these patients developed grade III
      IV lymphopenia [median lymphocyte counts fell from 1590 to 490 cell/mm3 (p <
      0.001)] which persisted throughout one year of observation. CONCLUSION: Severe
      and prolonged TRL is common in rectal cancer. Further studies are required to
      determine TRL's relationship to survival.

PMID- 30095292
TI  - Symmetry Breaking in the Mammalian Embryo.
AB  - We present an overview of symmetry breaking in early mammalian development as a
      continuous process from compaction to specification of the body axes. While
      earlier studies have focused on individual symmetry-breaking events, recent
      advances enable us to explore progressive symmetry breaking during early
      mammalian development. Although we primarily discuss embryonic development of the
      mouse, as it is the best-studied mammalian model system to date, we also
      highlight the shared and distinct aspects between different mammalian species.
      Finally, we discuss how insights gained from studying mammalian development can
      be generalized in light of self-organization principles. With this review, we
      hope to highlight new perspectives in studying symmetry breaking and self
      organization in multicellular systems.

PMID- 30095294
TI  - The association between obesity indices and hypertension: Which index is the most
      notable indicator of hypertension in different age groups stratified by sex?
AB  - OBJECTIVE: This study aimed to investigate the most notable obesity index and its
      optimal cut-off point of hypertension in different age groups stratified by sexes
      among community residents in southern China. METHODS: In this cross-sectional
      study, 620 men and 631 women aged 18-59 years were enrolled. The independent
      samples t-test and chi-square test were conducted to analyze continuous and
      categorical variables, respectively. Multivariate logistic regression analysis
      and receiver operating characteristic (ROC) curve analysis assessed the
      association between the obesity indices and hypertension risk. RESULTS: Waist
      stature ratio (WSR) and waist-hip ratio (WHR) were the most notable risk factors
      for hypertension in young men and women, respectively. The odds ratios (ORs) of
      hypertension risk increased with per standard deviation (SD) in WSR and WHR (WSR:
      OR = 2.877, 95% confidence interval [CI] = 1.602 to 5.167; WHR: OR = 10.683,
      95%CI = 2.179 to 52.376). In the middle-aged group of both sexes, body mass index
      (BMI) was the most distinctive risk factor for hypertension, the ORs of
      hypertension risk increased with per SD in BMI (men: OR = 2.297, 95%CI = 1.683 to
      3.136; women: OR = 1.810, 95%CI = 1.338 to 2.450). ROC curve analysis
      demonstrated WSR and PI were better indicators than other indices among young
      men, and WSR was the best marker among young women. However, BMI and WC were the
      most sensitive markers in middle-aged men and women, respectively. CONCLUSIONS:
      In this Chinese population, the association of obesity indices and hypertension
      is inconsistent in different age groups and sexes. It is important to choose
      appropriate indicators for specific groups of people.

PMID- 30095295
TI  - ABNORMAL ABSORPTIVE COLONIC MOTOR ACTIVITY IN GERM FREE MICE IS RECTIFIED BY
      BUTYRATE, AN EFFECT POSSIBLY MEDIATED BY MUCOSAL SEROTONIN.
AB  - The role of short-chain fatty acids (SCFAs) in colonic motility is controversial.
      Germ free (GF) mice are unable to produce these metabolites and serve as a model
      to study how their absence affects colonic motility. GF transit is slower than
      controls and colonization of these mice improves transit and serotonin (5-HT)
      levels. Our aim was to determine the role SCFAs play in improving transit, and
      whether this is dependent on mucosal 5-HT signaling. Motility was assessed in GF
      mice via spatiotemporal mapping using two techniques. The first measured motor
      patterns under intraluminal perfusion of phosphate buffer (PBS) with or without
      SCFA. In addition, outflow from the colon was recorded to quantify outflow due to
      individual propulsive contractions. The second technique measured fecal pellet
      propulsion using artificial pellets. Motility was then assessed in TPH1 KO mice,
      devoid of mucosal 5-HT, with PBS, butyrate and propionate intraluminal perfusion.
      GF mice exhibited a lower proportion of propulsive contractions, lower volume of
      outflow/contraction, slower velocity of contractions and slower propulsion of
      fecal pellets compared to controls. SCFAs changed motility patterns to that of
      the controls in all parameters. Butyrate administration increased the proportion
      of propulsive contractions in controls, yet failed to in TPH1 KO mice. Propionate
      inhibited propulsive contractions in all mice. Our results reveal significant
      abnormalities in the propulsive nature of colonic motor patterns in GF mice,
      explaining the decreased transit time in in vivo studies. We show that butyrate,
      and not propionate, activates propulsive motility and that this may require
      mucosal 5-HT.

PMID- 30095296
TI  - In the Setting of Beta Cell Stress, the Pancreatic Duct Gland Transcriptome Shows
      Characteristics of an Activated Regenerative Response.
AB  - The pancreatic duct gland (PDG) compartment has been proposed as a potential stem
      cell niche based on its coiled tubular structure embedded in mesenchyme, its
      proliferation and expansion in response to pancreatic injury, and the fact that
      it contains endocrine and exocrine epithelial cells. Little is known of the
      molecular signature of the PDG compartment in either a quiescent state or the
      potentially activated state during beta cell stress characteristic of diabetes.
      To address this, we performed RNA sequencing on RNA obtained from PDGs of wild
      type versus pre-diabetic HIP rats, a model of type 2 diabetes. The transcriptome
      of the PDG compartment, compared to a library of 84 tissue types, placed PDGs
      midpoint between the exocrine and endocrine pancreas and closely related to
      seminiferous tubules, consistent with a role as a stem cell niche for the
      exocrine and endocrine pancreas. Standard differential expression analysis
      (permissive threshold p<0.005) identified 245 genes differentially expressed in
      PDGs from HIP rats versus WT rats, with overrepresentation of transcripts
      involved in acute inflammatory responses, regulation of cell proliferation, and
      tissue development, while pathway analysis pointed to enrichment of cell movement
      related pathways. In conclusion the transcriptome of the PDG compartment is
      consistent with a pancreatic stem cell niche that is activated by ongoing beta
      cell stress signals. The documented PDG transcriptome provides potential
      candidates to be exploited for lineage tracing studies of this as yet little
      investigated compartment.

PMID- 30095293
TI  - Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and
      Fission Complexes.
AB  - The endosomal sorting complexes required for transport (ESCRT) pathway mediates
      cellular membrane remodeling and fission reactions. The pathway comprises five
      core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble
      complexes are typically recruited to target membranes by site-specific adaptors
      that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT
      II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane
      bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments
      and Vps4 remodel and sever membranes. Here, we review recent advances in our
      understanding of the structures, activities, and mechanisms of the ESCRT-III and
      Vps4 machinery, including the first high-resolution structures of ESCRT-III
      filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the
      discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside
      in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated
      membrane fission.

PMID- 30095297
TI  - Endotoxemia-enhanced renal vascular reactivity to endothelin-1 in cirrhotic rats.
AB  - Hepatorenal syndrome (HRS), a severe complication of advanced cirrhosis, is
      defined as hypoperfusion of kidneys resulting from intense renal vasoconstriction
      in response to generalized systemic arterial vasodilatation. Nevertheless, the
      mechanisms have been barely investigated. Cumulative studies demonstrated renal
      vasodilatation in portal hypertensive and compensated cirrhotic rats. Previously,
      we identified that blunted renal vascular reactivity of portal hypertensive rats
      was reversed after lipopolysaccharide (LPS). This study was therefore conducted
      to delineate the sequence of renal vascular alternation and underlying mechanisms
      in LPS-treated cirrhotic rats. Sprague-Dawley rats were randomly allocated to
      receive sham surgery (Sham) or common bile duct ligation (CBDL). LPS was induced
      on the 28th day after surgery. Kidney perfusion was performed at 0.5 or 3 h after
      LPS to evaluate renal vascular response to endothelin-1 (ET-1). Endotoxemia
      increased serum ET-1 levels ( P < 0.0001) and renal arterial blood flow ( P <
      0.05) in both Sham and CBDL rats. CBDL rats showed enhanced renal vascular
      reactivity to ET-1 at 3 h after LPS ( P = 0.026). Pretreatment with endothelin
      receptor type A (ETA) antagonist abrogated the LPS-enhanced renal vascular
      response in CBDL rats ( P < 0.001). There were significantly lower inducible
      nitric oxide synthase (iNOS) expression but higher ETA and phosphorylated
      extracellular signal-regulated kinase (p-ERK) expressions in renal medulla of
      endotoxemic CBDL rats ( P < 0.05). We concluded that LPS-induced renal iNOS
      inhibition, ETA upregulation, and subsequent ERK signaling activation may
      participate in renal vascular hyperreactivity in cirrhosis. ET-1-targeted therapy
      may be feasible in the control of HRS. NEW & NOTEWORTHY Hepatorenal syndrome
      (HRS) occurred in advanced cirrhosis after large-volume paracentesis or bacterial
      peritonitis. We demonstrated that intraperitoneal lipopolysaccharide (LPS)
      enhanced renal vascular reactivity to endothelin-1 (ET-1) in cirrhotic rats,
      accompanied by inducible nitric oxide synthase inhibition, endothelin receptor
      type A (ETA) upregulation, and subsequent extracellular signal-regulated kinase
      activation in renal medulla. Pretreatment with ETA antagonist abrogated the LPS
      enhanced renal vascular response in common bile duct ligation rats. These
      findings suggest that further clinical investigation of ET-1-targeted therapy may
      be feasible in the control of HRS.

PMID- 30095298
TI  - Ground flaxseed reverses protection of a reduced fat diet against Citrobacter
      rodentium-induced colitis.
AB  - Flaxseed is high in omega-3 polyunsaturated fatty acids, fiber and lignans known
      to lower cholesterol levels. However, its use for prevention or treatment of
      inflammatory bowel diseases has yielded mixed results, perhaps related to dietary
      interactions. In this study, we evaluated the impact of ground flaxseed
      supplementation on the severity of Citrobacter rodentium-induced colitis in the
      setting of either a high fat (HF; ~36 %kcal) or reduced fat (RF; ~12 %kcal) diet.
      After weaning, C57BL/6 mice (n=8-15/treatment) were fed ground flaxseed (7g/100g
      diet) with either HF (HF Flx) or RF (RF Flx) diets for four weeks prior to
      infection with C. rodentium or sham gavage. Weight changes, mucosal inflammation,
      pathogen burden, gut microbiota composition, tissue polyunsaturated fatty acids
      and cecal short-chain fatty acids were compared over a 14-day infection period. A
      RF diet protected against C. rodentium-induced colitis, whereas a RF Flx diet
      increased pathogen burden, exacerbated gut inflammation and promoted gut
      dysbiosis. Compared with a RF diet, both HF and HF Flx diets resulted in more
      severe pathology in response to C. rodentium infection. Our findings demonstrate
      that although a RF diet protected against C. rodentium-induced colitis and
      associated gut dysbiosis in mice, beneficial effects were diminished with ground
      flaxseed supplementation.

PMID- 30095299
TI  - High fat diet overfeeding promotes non-detrimental liver steatosis in female
      mice.
AB  - High fat diet (HFD) feeding or leptin deficient mice are extensively used as
      models resembling features of human non-alcoholic fatty liver disease (NAFLD).
      The concurrence of experimental factors as fat content and source or total
      caloric intake leads to prominent differences in the development of the hepatic
      steatosis and related disturbances. In this work, we characterized the hepatic
      lipid accumulation induced by HFD in wild type (Wt) and ob/ob mice with the
      purpose of differentiating adaptations to HFD from those specific of increased
      overfeeding due to leptin deficiency-associated hyperphagia. Given that most
      published works have been done in male models, we used female mice with the aim
      of increasing the body of evidence regarding NAFLD in female subjects. HFD
      promoted liver lipid accumulation only in the hyperphagic strain. Nevertheless, a
      decrease of lipid droplet-associated cholesteryl ester (CE) in both Wt and obese
      animals was observed. These changes were accompanied by an improvement in the
      profile of lipoproteins that transport cholesterol and liver function markers in
      plasma from ob/ob mice and a lower hepatic index. Using primary hepatocytes from
      female mice, over accumulation of CE induced by 0.4 mM oleic acid reversed in the
      presence of a specific Takeda G-protein-coupled bile acid receptor (TGR5)
      agonist. Nevertheless, hepatocytes from male mice were not responsive. This study
      suggests that enterohepatic circulation of bile acids might be one of the factors
      that can affect sex dimorphism in NAFLD development, which underlines the
      importance of including female models in NAFLD research field.

PMID- 30095300
TI  - Two Case Reports of Neuropsychological Outcomes following Pediatric anti-N-methyl
      D-aspartate Receptor Autoimmune Encephalitis.
AB  - Anti-NMDAR autoimmune encephalitis is a rare neurological condition. Limited
      existing pediatric case studies have shown mild, but persisting,
      neuropsychological impairments. This report described neuropsychological
      functioning in two patients treated for anti-NMDAR autoimmune encephalitis.
      Patient A is a 16-year-old male (10 months after symptom onset) and Patient B is
      a 5-year-old female (45 months after symptom onset). Contrary to expectations,
      their cognitive profiles were largely intact, raising the possibility of minimal
      cognitive implications for some pediatric patients with this condition.
      Additional research is needed to identify factors that contribute to better
      cognitive outcomes in children with anti-NMDAR autoimmune encephalitis.

PMID- 30095301
TI  - Extracellular esterase activity as an indicator of endoplasmic reticulum calcium
      depletion.
AB  - CONTEXT: Endoplasmic reticulum (ER) calcium depletion is associated with diverse
      diseases, including cardiac, hepatic, and neurologic diseases. OBJECTIVE: The aim
      of the present study was to identify and characterize an endogenous protein that
      could be used to monitor ER calcium depletion comparably to a previously
      described exogenous reporter protein. MATERIALS AND METHODS: The use of a
      selective esterase-fluorescein diester pair allowed for carboxylesterase activity
      in extracellular fluid to be measured using a fluorescent readout. Cell culture
      media from three different cell lines, rat plasma, and human serum all possess
      quantifiable amounts of esterase activity. RESULTS: Fluorescence produced by the
      interaction of carboxylesterases with a fluorescein diester substrate tracks with
      pharmacological and physiological inducers of ER calcium depletion. The
      fluorescence measured for in vitro and in vivo samples were consistent with ER
      calcium depletion being the trigger for increased esterase activity. DISCUSSION:
      Decreased luminal ER calcium causes ER resident esterases to be released from the
      cell, and, when assessed concurrently with other disease biomarkers, these
      esterases may provide insight into the role of ER calcium homeostasis in human
      diseases. CONCLUSION: Our results indicate that carboxylesterases are putative
      markers of ER calcium dysfunction.

PMID- 30095304
TI  - The Use of Patient-Reported Outcomes Measures: Secondary School Athletic
      Trainers' Perceptions, Practices, and Barriers.
AB  - CONTEXT: : Incorporating patient-reported outcomes (PROs) into daily routine is
      essential for patient-centered clinical practice. Secondary school athletic
      trainers (ATs) may encounter unique barriers that limit their willingness to use
      PROs. OBJECTIVE: : To explore how secondary school ATs who were using PROs
      perceived their application, benefits, and problems compared with those who did
      not. DESIGN: : Cross-sectional study. SETTING: : Web-based survey. PATIENTS OR
      OTHER PARTICIPANTS: : A total of 2984 secondary school ATs received an e-mail
      invitation, and 322 completed the survey (response rate = 10.8%). Respondents
      were 43 +/- 10 years old, with most indicating at least 11 years as a Board of
      Certification-certified AT (n = 276, 85.7%). MAIN OUTCOME MEASURE(S): : The ATs
      were invited to complete a Web-based survey regarding the uses and benefits of
      and problems with PROs. Those using PROs in clinical practice were asked their
      criteria for selecting the measures, whereas those not using PROs were asked
      their reasons for not using them. Dependent variables were endorsements of uses
      and benefits of and problems with PROs. RESULTS: : The most commonly cited uses
      of PROs were determining treatment effectiveness (193/264, 73%) and demonstrating
      effectiveness to administration (174/264, 66%). Improving communication with the
      patient (267/296, 90%) and helping to direct the plan of care (256/297, 86%) were
      the most frequently endorsed benefits of PROs. Time to score and analyze
      (152/284, 53%) and time for patients to complete (134/284, 47%) PROs were the
      problems encountered most often. For ATs not using PROs (223/262, 85%), the most
      frequent reason was the lack of a support structure (102/219, 46%). For ATs using
      PROs (39/262, 15%), quick completion times (32/39, 82%) was the most common
      criterion used to select individual measures. CONCLUSIONS: : A majority of
      secondary school ATs recognized the benefits of PROs and yet did not use them in
      clinical practice due to setting-specific barriers.

PMID- 30095302
TI  - Short and Medium Latency Responses in Participants With Chronic Ankle
      Instability.
AB  - CONTEXT:   The determinant role of medium latency responses (MLRs) during
      compensatory postural adjustments in postural stability and the lack of clarity
      about the mechanisms behind chronic ankle instability (CAI) sustain the
      hypothesis that these postural responses are impaired in this condition. However,
      to the best of our knowledge, no authors have assessed MLRs in patients with CAI;
      most of the research regarding compensatory postural adjustments has been
      directed at the timing of short latency responses (SLRs). OBJECTIVE:   To
      evaluate bilateral compensatory postural responses, including SLRs and MLRs, in
      response to a unilateral simulated ankle-sprain mechanism in participants with
      CAI. DESIGN:   Case-control study. SETTING:   Laboratory. PATIENTS OR OTHER
      PARTICIPANTS:   Twenty-four participants with CAI and 20 controls.
      INTERVENTION(S):   Bilateral electromyography of the peroneus longus (PL),
      peroneus brevis, tibialis anterior (TA), and soleus (SOL) muscles was collected
      during a unilateral sudden-inversion perturbation (30 degrees ). MAIN OUTCOME
      MEASURE(S):   Muscle-onset activations and magnitudes of SLRs and MLRs in the
      support and perturbed positions. RESULTS:   Participants with CAI showed (1)
      later-onset activation of the TA and SOL in the uninjured limb and bilateral
      decreases in the magnitude of the TA MLR in the support position, (2) increased
      magnitude of the PL MLR in the uninjured limb in the support and perturbed
      positions, and (3) increased magnitude of the PL SLR and MLR in the injured limb
      in the perturbed position. CONCLUSIONS:   Chronic ankle instability was
      associated with later TA and SOL activation in the uninjured limb and bilaterally
      decreased magnitude of the TA MLR in the support position.

PMID- 30095303
TI  - The Lived Experiences of Retired Collegiate Athletes With a History of 1 or More
      Concussions.
AB  - CONTEXT:   Concussions remain misunderstood, underreported, and undiagnosed.
      Although most concussion symptoms resolve within 2 weeks, some patients
      experience persistent symptoms that adversely affect physical, emotional, social,
      or cognitive functioning or a combination of these. Minimal evidence delineating
      the effect of concussions on recently retired collegiate athletes currently
      exists. OBJECTIVE:   To examine the lived experiences of retired collegiate
      athletes with a history of 1 or more concussions to discern individual concussion
      histories, knowledge and perceptions of concussions, and postconcussion quality
      of life. DESIGN:   Qualitative study. SETTING:   Telephone interviews. PATIENTS
      OR OTHER PARTICIPANTS:   Former National Collegiate Athletic Association Division
      I athletes (n = 14) with a history of 1 or more concussions and retired from 1 to
      5 years. DATA COLLECTION AND ANALYSIS:   Fourteen semistructured telephone
      interviews (8 men and 6 women) were audiotaped. Interviews were transcribed and
      inductively analyzed by 3 athletic trainers with 34 combined years of
      professional experience. Themes were negotiated through consensual review.
      Participant checks were completed to ensure trustworthiness of the findings.
      RESULTS:   Participants sustained their first concussion during adolescence and
      often experienced difficulties transitioning back into the postconcussion
      academic environment. Judgments of injury severity were clearly evident in
      participants' knowledge and perceptions of concussions. Participants experienced
      an array of emotional, physical, cognitive, and social challenges during the
      immediate postconcussion period but did not feel their concussion history
      decreased their current quality of life. CONCLUSIONS:   Adolescent exposure to
      concussions is of concern due to the risk imposed on the developing brain and the
      potential for adverse outcomes later in life. Although a graduated return to play
      is heavily emphasized in concussion management, researchers need to investigate
      barriers inhibiting the implementation of return-to-learn protocols. Concussion
      education should aim to modify indifferent attitudes toward concussive injuries.
      Additionally, investigators should continue to assess how a history of concussion
      affects quality of life in recently retired collegiate athletes.

PMID- 30095305
TI  - Isotherm and kinetic modelling of Toluidine Blue (TB) removal from aqueous
      solution using Lemna minor.
AB  - The aim of this study was to investigate the ability of Lemna minor for Toluidine
      Blue (TB) removal. Influence of the initial concentration over the removal
      process was considered. Experimental data have been analyzed using Langmuir,
      Freundlich, Dubinin-Radushkevich (D-R), and Elovich isotherm models. In addition,
      several kinetic models, pseudo-first-, pseudo-second-order, intraparticle and
      film diffusion models were considered. Langmuir and Freundlich isotherm suggested
      a favorable adsorption of TB by Lemna minor plants. From the D-R the mean free
      energy was calculated to be 11.18 kJ/mol, which indicates that TB adsorption was
      characterized by a chemisorption process. Kinetic studies showed that liquid film
      diffusion plays an important role during the process. Adsorption capacities of up
      to 26.69 mg/g and a high capacity of adaptation indicated that phytoremediation
      using Lemna minor could be a valuable alternative for dyes removal from
      wastewaters.

PMID- 30095306
TI  - Evaluation of Spinacia oleracea (L.) for phytodesalination and augmented
      production of bioactive metabolite, 20-hydroxyecdysone.
AB  - In this study, adaptive features of Spinacia oleracea to different levels of
      salinity, its use in desalination and production of 20-Hydroxyecdysone were
      studied. Plants showed survival up to EC 12 dS/m with reduced growth as compared
      with control. Net photosynthesis rate, transpiration, stomatal conductance, and
      water use efficiency of salt treated plants declines with increasing salinity
      stress. Higher antioxidant enzyme activities and compatible solutes accumulation
      were observed in salt treated plants as function of osmotic adjustment.
      Significant Na+ sequestration and Na/K ratio were noted with increase in salt
      stress in comparison to the control. Since the plant accumulates a bioactive,
      secondary metabolite 20-Hydroxyecdysone (20E), we observed significant 20E
      content in plants grown at EC 4-12 dS/m in comparison to control. Furthermore, a
      preliminary field experiment, showed significant reduction in the soil electrical
      conductivity by 1.8 ds/m after 90 days of plant growth with Na+ sequestration in
      plant biomass. Subsequent to this growth period, the phytodesalinized soil
      supported the significant growth of a glycophyte (rice). Our results suggest that
      S. oleracea can adapt to saline conditions with antioxidant defense and osmotic
      adjustment. The plant can be used as a potential candidate for desalination and
      also for enhanced production of 20-Hydroxyecdysone.

PMID- 30095307
TI  - Influence of alkyl polyglucoside, citric acid, and nitrilotriacetic acid on
      phytoremediation in pyrene-Pb co-contaminated soils.
AB  - At present, the remediation for organic pollutants and heavy metals co
      contaminated soils is a challenge which needs to be broken through. In this
      study, alkyl polyglucoside (APG), citric acid (CA), and nitrilotriacetic acid
      (NTA) were chosen to enhance the phytoremediation of pyrene and Pb co
      contaminated soils by perennial ryegrass. Through the comparison of the results
      with different applications, it could be found that the application of NTA was
      beneficial to the growth of perennial ryegrass, the underground and aboveground
      biomass were increased by 172.9-236.1% and 61.9-142.8%, respectively, meanwhile,
      photosynthetic activity of perennial ryegrass was affected positively. More
      importantly, the combined application of APG and NTA maximally promoted the
      accumulation and translocation of Pb (BF/TF, 0.44/0.61) and dissipation of pyrene
      (71.6%). These results indicated that the combined application of APG and NTA
      could be promising for future practical application of phytoremediation. However,
      the optimal dosage ratio of APG and NTA for phytoremediation needs to be further
      researched.

PMID- 30095308
TI  - Adsorption of cationic dye from aqueous solutions by date pits: Equilibrium,
      kinetic, thermodynamic studies, and batch adsorber design.
AB  - The retention profile of methylene blue from aqueous solutions onto the solid
      adsorbent date pits has been investigated in a batch system. The characterization
      and adsorption efficiency for methylene blue was evaluated using date pits.
      Fourier Transform Infra-Red, Scanning Electron Microscope, Brunauer-Emmett-Teller
      analysis were performed to determine the characteristics of the material. The
      effect of contact time, initial dye concentration, adsorbent dosage, temperature,
      and solution pH were investigated. The adsorption was found to increase with
      increasing time, decreasing concentration of dye, decreasing temperature and
      increasing dosage up to equilibrium values which was 20 min, 25 degrees C, and
      0.1 g adsorbent, respectively. The adsorption was favorable at high and low pH
      (pH 3, pH 7). The adsorption equilibrium data were best fitted by Freundlich
      isotherm. The adsorption kinetics was found to follow the pseudo second order
      kinetic model. Thermodynamic parameters such as free energy, enthalpy, and
      entropy were calculated and found to be -4.6 kJ/mole, -7.9 kJ/mole, and -11.8
      kJ/mole, respectively. The thermodynamic parameters of the uptake of methylene
      blue onto the date pits indicated that, the process is exothermic and proceeds
      spontaneously at low temperature. A single stage batch adsorber was designed for
      adsorption of methylene blue by Date Pits based on optimum isotherm.

PMID- 30095309
TI  - Prospect of phytoaccumulation of arsenic by Brassica juncea (L.) in Bangladesh.
AB  - The phytoaccummulation of arsenic by Brassica juncea (L.) was investigated for
      varying concentrations selected within the range that is evident in Bangladeshi
      soil. B. juncea (Rai and BARI-11) was grown in the hydroponic media under
      greenhouse condition with different concentrations (0.5, 1.0, 15, 30, 50 and 100
      ppm) of sodium arsenite. Inductively coupled plasma atomic emission spectroscopy
      (ICP-AES) was used to analyze the data. Mapping of potential area of
      phytoaccumulation of arsenic by B. juncea was done using Geographic information
      system (GIS). Arsenic was detected at lower concentrations (0.5 and 1.0 ppm) only
      at root system of the plant. For higher concentrations (15, 30, and 50 ppm)
      arsenic was detected both in the root and shoot systems. The results suggested
      that at 15 and 50 ppm uptake was higher compared to 30 ppm. For 100 ppm of
      arsenic no plant growth was observed. In Bangladesh, where concentration of
      arsenic is at lower level and present only at rooting zone, B. juncea may be used
      for phytoaccumulation of arsenic keeping usual agronomic practices. However, for
      higher concentrations, B. juncea can be regarded as a good accumulator of arsenic
      where uptake of arsenic was up to 1% of total biomass of the plant.

PMID- 30095310
TI  - A rapid method for harvesting and immobilization of oleaginous microalgae using
      pellet-forming filamentous fungi and the application in phytoremediation of
      secondary effluent.
AB  - A rapid method for harvesting and immobilization of oleaginous microalgae using
      pellet-forming filamentous fungi was developed. The suitable conditions for
      pellet formation by filamentous fungi were determined. Among the strains tested,
      Trichoderma reesei QM 9414 showed superior pellet forming ability. Its pellets
      were used to harvest oleaginous microalga Scenedesmus sp. With increasing volume
      ratio of fungal pellets to microalgae culture up to 1:2, >94% of microalgal cells
      were rapidly harvested within 10 min. The ratio of fungal pellets could
      manipulate both harvesting time and initial concentration of microalgal cells in
      the pellets. The microalgae-fungal pellets were successfully used as immobilized
      cells for effective phytoremediation of secondary effluent from seafood
      processing plants under nonsterile condition. The chemical oxygen demand, total
      nitrogen, and total phosphorus removal were >74%, >44%, and >93%, respectively.
      The scanning electron microscopy showed that the microalgal cells were not only
      entrapped in the pellets but also got attached to the fungal hyphae with sticky
      exopolysaccharides, possibly secreted by the fungi. The extracted lipids from the
      pellets were mainly composed of C16-C18 (>83%) with their suitability as
      biodiesel feedstocks. This study has shown the promising strategy to rapidly
      harvest and immobilize microalgal cells and the possible application in
      phytoremediation of industrial effluent.

PMID- 30095311
TI  - Human health risks from consuming cabbage (Brassica oleracea L. var. capitata)
      grown on wastewater irrigated soil.
AB  - The present study investigated the impact of cumulative irrigation with
      wastewater on the soil properties and, its health hazards on the consumers of
      cabbage plants at south Cairo Province, Egypt. Irrigation water, soil and cabbage
      plants were sample d from two polluted and other two unpolluted farms. The
      physicochemical properties of water and soil were analyzed and the growth
      parameters, as well as nutrients and heavy metals concentration in cabbage were
      investigated. In addition, the daily intake of metals (DIM) and health risk index
      (HRI) were estimated. Wastewater posed a decrease in the availability of N, P and
      K, but increases heavy metals in the soil solution. Cabbage stem and root lengths
      as well as the number of leaves and biomass were greatly reduced in the polluted
      farms. In addition, the photosynthetic pigments, carbohydrates and proteins were
      decreased under pollution stress. The concentration of most investigated metals
      in the leaves and roots were increased with translocation factor greater than one
      for Pb, Cd, As, Cr, Ni, Fe, and Co. The study revealed that the HRI exceeded one
      for Pb and Cd in polluted and unpolluted plants; and Fe in polluted ones.
      Irrigation with wastewater is not suitable for cabbage as it has health risks on
      humans due to accumulation of heavy metals. It worth noting that, the high
      ability of cabbage plants to accumulate Pb and Cd from both polluted and
      unpolluted soils should be taken into consideration when consuming this plant.

PMID- 30095312
TI  - Comparison of Distichlis spicata and Suaeda aegyptiaca in response to water
      salinity: Candidate halophytic species for saline soils remediation.
AB  - Distichlis spicata and Suaeda aegyptiaca are two potential halophytic plant
      species for bioremediation of salt degraded soils, and development of saline
      agriculture. The physiological responses of the species to different levels of
      salinity (EC 0, 12, 24, 36, and 48 dS/m) in a controlled environment experiment
      were studied. Both species showed a high level of tolerance to elevated
      concentrations of salt in the irrigation water. The shoot fresh and dry weights
      in S. aegyptiaca increased till 36 dS/m and were sustained under 48 dS/m while in
      D. spicata, both parameters decreased as salinity increased. Glycine betaine
      accumulation did not change in D. spicata with increasing salinity, whereas
      proline content revealed a marked increase of 7.13 fold in 48 dS/m salinity
      compared to the control, which showed its critical osmoprotection role in the
      plant. In S. aegyptiaca, both osmolytes content significantly increased at high
      salinity levels (36 and 48 dS/m) up to 3.22 and 2.0 folds, respectively. Overall,
      S. aegyptiaca had a better potential of Na+ phytoremediation, and tolerated
      higher salinity compared to D. spicata. In contrast, the vigorous root and
      rhizome growth in D. spicata made it a proper solution for protecting the soils
      against further erosion under saline conditions.

PMID- 30095313
TI  - The chelating effect of citric acid, oxalic acid, amino acids and Pseudomonas
      fluorescens bacteria on phytoremediation of Cu, Zn, and Cr from soil using Suaeda
      vera.
AB  - Phytoextraction is a green technique for the removal of soil contaminants by
      plants uptake with the subsequent elimination of the generated biomass. The
      halophytic plant Suaeda vera Forssk. ex J.F.Gmel. is an native Mediterranean
      species able to tolerate and accumulate salts and heavy metals in their tissues.
      The objective of this study was to explore the potential use of S. vera for soil
      metal phytoextraction and to assess the impact of different chelating agents such
      as natural organic acids (oxalic acid [OA], citric acid [CA]), amino acids (AA)
      and Pseudomonas fluorescens bacteria (PFB) on the metal uptake and translocation.
      After 12 months, the highest accumulation of Cu was observed in the root/stem of
      PFB plots (17.62/8.19 mg/kg), in the root/stem of CA plots for Zn (31.16/23.52
      mg/kg) and in the root of OA plots for Cr (10.53 mg/kg). The highest accumulation
      of metals occurred in the roots (27.33-50.76 mg/kg). Zn was the metal that
      accumulated at the highest rates in most cases. The phytoextraction percentages
      were higher for Cu and Zn (~2%) with respect to Cr (~1%). The percentages of
      metal removal from soil indicate the need to monitor soil properties, to
      recognize the influence of each treatment and to increase the concentration of
      bioavailable metals by the use of agricultural management practices aimed at
      promoting plant growth.

PMID- 30095314
TI  - Compared the physiological response of two petroleum tolerant-contrasting plants
      to petroleum stress.
AB  - Petroleum not only benefits the world economy but also contaminates the soil. In
      order to select the plants tolerant to petroleum, the physiological response of
      two petroleum tolerant-contrasting plants, Mirabilis jalapa and Orychophragmus
      violace, were investigated in variation of petroleum-contaminated soils (0, 5,
      10, 20, and 40 g petroleum per kg soil) for 120 d. Petroleum degradation rate,
      seeds germination rate, free proline, and superoxide dismutase and peroxidase
      activities of M. jalapa were higher than that of O. violace under petroleum
      stress. However, the decrease rate of soluble protein, plant height, chlorophyll,
      and root fresh weight was greater in O. violace as compared to M. jalapa. Pearson
      correlation coefficient analysis was conducted, which indicated that the higher
      tolerance of M. jalapa was correlated with the higher level of free proline and
      antioxidative enzyme activities. Besides, the 10 g petroleum per kg soil may be
      appropriate for petroleum-tolerant plants selection, in which petroleum
      significantly restrain growth in O. violace but not in M. jalapa.

PMID- 30095315
TI  - An update on the treatment of Restless Legs Syndrome/Willis-Ekbom Disease:
      prospects and challenges.
AB  - INTRODUCTION: Restless Legs Syndrome/Willis-Ekbom Disease (RLS/WED) is a sleep
      disorder characterized by an urge to move the legs, frequently associated or
      triggered by unpleasant sensations in the lower limbs that affects approximately
      2.5% of adults. Therapy and management of RLS/WED require long-term
      interventions, since the typical manifestation of this disorder is chronic. Areas
      covered: In this review, we provide an update regarding the treatment of RLS/WED
      with particular attention to future challenges for its management. We reviewed a
      large variety of treatments studied in clinical trials and supported by the most
      updated guidelines. Alongside with first-line interventions other pharmacological
      options including opioids, benzodiazepines, iron therapy, and newly studied drugs
      are discussed. Furthermore, due to the occurrence of augmentation and worsening
      of symptoms we also reviewed the development of non-pharmacologic alternatives.
      Expert commentary: The management of RLS/WED is a challenge because of different
      long-term issues. Several complications, such as loss of the therapeutic effect
      of dopaminergic or non-dopaminergic agents and augmentation, are still unsolved
      concerns. However, the development of new drugs acting on adenosinergic and
      glutamatergic neurotransmission seems promising. Randomized controlled trials are
      needed in order to recognize effectiveness of new drugs or non-pharmacological
      treatment strategies.

PMID- 30095316
TI  - Ocular Nocardiosis: A Case Report.
AB  - PURPOSE: To describe the challenging diagnosis of ocular nocardiosis in a patient
      with anaplastic astrocytoma Methods: A 56-year-old patient with recurrent
      cerebral anaplastic astrocytoma and a history of surgical resection, who
      underwent radiotherapy and chemotherapy, presented with a unilateral white
      subretinal mass at the posterior pole of his left eye. Vitrectomy and fine-needle
      biopsy of the vitreous as well as the subretinal mass were performed. RESULTS:
      Magnetic resonance imaging verified progression of the lesion's size at follow
      up. Histopathological workup of the material revealed gram-positive filamentous
      bacteria consistent with Nocardia cyriacigeorgica. CONCLUSION: Endogenous
      Nocardia should be suspected in case of choroidal abscess in immunocompromised
      patients. Clinical diagnosis is challenging; therefore, early subretinal biopsy
      should be considered to facilitate treatment decision.

PMID- 30095317
TI  - Recent development of enterovirus A vaccine candidates for the prevention of
      hand, foot, and mouth disease.
AB  - INTRODUCTION: Hand, foot, and mouth disease (HFMD) is a childhood illness
      commonly caused by enterovirus A. Enterovirus A71 (EV-A71) and coxsackievirus A16
      (CV-A16) are the most commonly identified viruses associated with HFMD. Recently,
      outbreaks caused by different enterovirus A including CV-A6 and CV-A10 are
      increasing. Being available now to protect against EV-A71 infection, inactivated
      EV-A71 vaccines cannot prevent coxsackievirus infections, thus limiting their
      general application in controlling HFMD. Multivalent HFMD vaccines are suggested
      to have broad cross-neutralizing responses against these emerging enteroviruses.
      Areas covered: We discuss the recent development of enterovirus A vaccines
      including the inactivated whole-virion vaccine and virus-like particle vaccine
      candidates and review the information of neutralization epitopes of these
      viruses. Expert commentary: Evaluation of the efficacy and safety of the
      coxsackievirus vaccine and the multivalent HFMD vaccine candidates in clinical
      trials is urgently required. Epitopic analysis showed that common immunodominant
      sites exist across these enteroviruses. However, variations of amino acid
      residues in these regions limit the induction of cross-neutralization antibodies,
      and therefore, a multivalent HFMD vaccine is required for broad protection
      against HFMD. With the inclusion of major circulating viruses in the development
      of multivalent HFMD vaccines, an increase in the success in HFMD control is
      anticipated.

PMID- 30095318
TI  - Relationship Between Platelet Count and Insulin Resistance in Korean Adolescents:
      A Nationwide Population-Based Study.
AB  - BACKGROUND: To examine the relationship between platelet count and insulin
      resistance, as measured by a homeostasis model assessment of insulin resistance
      (HOMA-IR), in a nationally representative sample of Korean adolescents. METHODS:
      The study population comprised 1133 participants (636 male and 497 female
      participants) aged 12-18 years selected from the 2008-2010 Korea National Health
      and Nutrition Examination Survey. Insulin resistance was defined as a HOMA-IR
      value greater than the 85th percentile. The odds ratios (ORs) and 95% confidence
      intervals (95% CIs) for insulin resistance were calculated using multiple
      logistic regression analysis. RESULTS: The mean values of insulin and HOMA-IR
      increased proportionally with platelet count quartiles for all, male, and female
      participants. The prevalence of insulin resistance increased significantly with
      an increase in platelet count quartiles in all, male, and female participants.
      Compared with the ORs for individuals in the lowest platelet count quartile, the
      ORs (95% CIs) for insulin resistance in individuals in the highest quartile was
      2.90 (1.39-6.07) for all, 2.98 (1.14-8.31) for male, and 2.14 (0.88-5.32) for
      female participants, after adjusting for age, gender (for all participants),
      household income, residential area, family history of diabetes mellitus, and
      overweight [85th percentile <= body mass index (BMI) <95th percentiles for age
      and gender] or obesity (BMI >=95th percentile). CONCLUSION: Platelet count was
      positively associated with insulin resistance in Korean adolescents. These
      findings suggest that platelet count could be a useful indicator for identifying
      adolescents with insulin resistance.

PMID- 30095319
TI  - A retrospective analysis of infections and antibiotic treatment in patients with
      Stevens-Johnson syndrome and toxic epidermal necrolysis.
AB  - BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
      are rare drug-related life-threatening acute conditions. Infection is a major
      cause of morbidity and mortality in these patients. The aim of this study was to
      analyze the infective characteristics and antimicrobial strategies in patients
      with Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
      METHODS: 125 patients who were diagnosed with SJS/TEN in West China Hospital from
      2010 to 2017 were retrospectively analyzed. RESULTS: There were 75 patients with
      coinfections (75/125, 60%), of whom 44 had SJS (44/90, 48.9%) and 31 had TEN
      (31/35, 88.6%). The most common infections were skin infections and pulmonary
      infections. Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) were
      the most frequently identified pathogenic organisms. The most common antibiotics
      used in patients with infections were vancomycin, carbapenems, quinolones,
      macrolides and lincomycin. CONCLUSIONS: Antimicrobial therapy should be
      administered promptly if there are clinical signs of an infection. Empiric
      antibiotic selection is based on knowledge of the local microbiota, the different
      infected sites, the pathogens involved and the severity of disease.

PMID- 30095320
TI  - Ultraviolet radiation and incidence of cataracts in a nationwide US cohort.
AB  - PURPOSE: We examine the risk of cataract and cataract surgery with measures of
      ultraviolet radiation (UVR) exposure and UVR sensitivity in a large, nationwide
      population of indoor workers. METHODS: Participants from the US Radiologic
      Technologists Study were followed from age at baseline survey (2003-2005) to age
      at earliest of cataract diagnosis, cataract surgery, or completion of last survey
      (2012-2013). UVR-related factors included satellite-based ambient UVR linked to
      lifetime residences, time spent outdoors across various age periods, history of
      blistering sunburns, prior diagnosis of keratinocyte carcinoma, and iris color.
      We used Cox proportional hazards models with age as timescale to compute hazard
      ratios (HRs) and 95% confidence intervals (CIs) for cataract and cataract
      surgery. RESULTS: Participants had a median age of entry of 54.0 years, were
      80.0% female, and 95.7% white. Of the 44, 891 eligible participants, 9399 cases
      of cataract and 3826 cases of cataract surgery were reported. Ambient UVR
      (quintile 5 vs. 1) was associated with an increased risk of cataract (HR = 1.08;
      95% CI: 1.01-1.16) and cataract surgery (HR = 1.16; 95% CI: 1.05-1.29). Lifetime
      average time spent outdoors was not associated with cataract risk. History of
      blistering sunburns before and after age 15, but not previous keratinocyte
      carcinoma diagnosis was associated with both cataract and cataract surgery.
      CONCLUSION: Our results suggest a modest role for residence-based ambient UVR and
      cataract risk among indoor workers in the United States.

PMID- 30095321
TI  - First Report of Cocksfoot Mottle Virus Infecting Dactylis glomerata in Forage
      Production Fields in California.

PMID- 30095322
TI  - First Report of Colletotrichum truncatum Causing Anthracnose on the Berry Stalk
      and the Rachis of Kyoho Grape (Vitis labruscana * V. vinifera) Clusters in Hebei,
      China.

PMID- 30095323
TI  - First Report of Citrus viroid V Naturally Infecting Grapefruit and Calamondin
      Trees in California.

PMID- 30095324
TI  - First Report of Lasiodiplodia theobromae Causing Rot in Eggplant Fruit in Brazil.

PMID- 30095325
TI  - Overview of knowledge, attitudes, beliefs, vaccine hesitancy and vaccine
      acceptance among mothers of infants in Quebec, Canada.
AB  - BACKGROUND: Vaccine hesitancy (VH) is a growing problem. The first step in
      addressing VH is to have an understanding of who are the hesitant individuals and
      what are their specific concerns. The aim of this survey was to assess mothers'
      level of vaccine hesitancy and vaccination knowledge, attitudes, and beliefs.
      METHODS: Mothers of newly-born infants in four maternity wards in Quebec (Canada)
      completed a self-administered questionnaire. The questionnaire included items to
      assess VH and intention to vaccinate. VH scores were calculated using the Parents
      Attitudes about Childhood Vaccines (PACV) survey. Multivariate logistic
      regression was performed to determine variables associated with intention to
      vaccinate (OR; 95% CI). RESULTS: Overall, 2645 questionnaires were included in
      this analysis and 77.5% of respondents certainly intended to vaccinate their
      infant at 2 months of age. Based on the PACV 100-point scale, 56.4% of mothers
      had a 0 to ?30 score (low level of VH); 28.6% had a 30 to ?50 and 15.0% had a
      score of 50 and higher (high level of VH).The main determinants of mothers'
      intention to vaccinate were the perceived importance of vaccinating infants at 2
      months of age (OR = 9.2; 5.9-14.5) and a low score of VH (OR = 7.4; 5.3-10.3).
      DISCUSSION: Although the majority of mothers held positive attitudes toward
      vaccination, a large proportion were moderately or highly vaccine hesitant.
      Mothers' level of VH was strongly associated with their intention to vaccinate
      their infants, showing the potential detrimental impact of VH on vaccine uptake
      rates and the importance of addressing this phenomenon.

PMID- 30095326
TI  - A novel co-existing ZCCHC8-ROS1 and de-novo MET amplification dual driver in
      advanced lung adenocarcinoma with a good response to crizotinib.
AB  - In non-small cell lung cancer (NSCLC), driver gene alterations, such as EGFR,
      ALK, MET, and ROS1, are usually mutually exclusive. Few clinical cases with co
      existing ROS1 fusion and de-novo MET amplification have been reported. In
      addition, the efficacy of crizotinib in Chinese patients with driver co-existing
      alterations is uncertain. A 65-year-old female was diagnosed with lung
      adenocarcinoma metastatic to the brain. She had sufficient tumor tissue for
      detection of the target gene; however, common driver gene mutations, such as EGFR
      wild and ALK-negative, were not initially detected. The patient was ultimately
      shown to have both ZCCHC8-ROS1 and de-novo MET gene amplification through next
      generation sequencing with sensitivity to the targeted therapy of crizotinib.
      Unfortunately, the progression-free survival was only 6 months in length. We
      report here the first patient with co-existing ROS1 fusion and de-novo MET
      amplification to receive crizotinib in China. Treatment of our patient was
      effective with targeted therapy based on a precise diagnosis. Advanced or
      metastatic NSCLC patients with co-existing ROS1 fusion and de-novo MET
      amplification are sensitive to crizotinib. These uncommon driver gene mutations
      may be missed using the current first-generation detection assay. We must be
      aware of the incidence of concomitant ROS1 fusion and de-novo MET amplification
      because NSCLC patients could benefit from targeted therapy.

PMID- 30095327
TI  - Physician Nonprofessional Cancer Experience and Ovarian Cancer Screening
      Practices: Results from a National Survey of Primary Care Physicians.
AB  - OBJECTIVE: Routine ovarian cancer screening is ineffective; therefore, no
      professional organization recommends this screening in asymptomatic patients.
      However, many physicians have recommended screening, exposing patients to
      unnecessary risk. Little research exists on how nonprofessional experience with
      cancer influences physicians' screening practices. This study examines the
      association between physicians' nonprofessional experience with cancer and
      reported adherence to ovarian cancer screening guidelines. MATERIALS AND METHODS:
      A mail questionnaire with an annual examination vignette and questions about
      cancer screening recommendations was sent to a random sample of 3,200 U.S. family
      physicians, general internists, and obstetrician-gynecologists. This analysis
      included 497 physicians who received a vignette of a woman at average ovarian
      cancer risk and weighted results to represent these physician groups nationally.
      The outcome measure was adherence to ovarian cancer screening guidelines.
      Stepwise multivariate logistic regression estimated adjusted risk ratios for
      guideline adherence. RESULTS: In unadjusted analyses, 86.0% of physicians without
      nonprofessional cancer experience reported adherence to ovarian cancer screening
      guidelines compared with 69.2% of physicians with their own history of cancer, or
      a family member or close friend/coworker with cancer (p = 0.0045). In adjusted
      analyses, physicians with cancer themselves or in a family member or close
      friend/coworker were 0.82 times less likely (CI: 0.73-0.92) to report adhering to
      ovarian cancer screening recommendations than those without nonprofessional
      cancer experience. CONCLUSIONS: Despite recommendations to the contrary, many
      physicians reported recommending ovarian cancer screening in low-risk women.
      Physicians with nonprofessional cancer experience were more likely to report
      offering or ordering nonrecommended screening than physicians without this
      experience.

PMID- 30095328
TI  - Providing Medical Assistance in Dying within a Home Palliative Care Program in
      Toronto, Canada: An Observational Study of the First Year of Experience.
AB  - BACKGROUND: Medical Assistance in Dying (MAiD) was legalized in Canada in June
      2016. There are no documented experiences of MAiD provision within a home
      palliative care program. The majority of palliative care physicians in Canada
      object to MAiD. As one of the largest home-based palliative care providers in
      Canada, the Temmy Latner Centre for Palliative Care (TLCPC) developed processes
      to implement MAiD provision within a home palliative care team with diverse
      attitudes toward MAiD. OBJECTIVE: To demonstrate the feasibility of providing
      MAiD within a home palliative care setting and describe the population that
      received MAiD in the first year of legalization. DESIGN: A retrospective chart
      review identified patients who received or were assessed for MAiD and had a known
      outcome between June 17, 2016 and June 30, 2017. SETTING/SUBJECTS: Patients
      receiving home-based palliative care. MEASUREMENTS: Data extracted included age,
      gender, primary diagnosis, length of time receiving home-based palliative care,
      and final clinical outcome. RESULTS: Of the 45 patients who were assessed for
      MAiD, 27 (60%) received MAiD and 18 (40%) did not. The mean age was 74 (range 20
      95), 24 (53%) were male, and 33 (73%) had cancer as a primary diagnosis. These 27
      patients represent 1.2% of our total patient population during this time period.
      CONCLUSIONS: MAiD was accessed by 1.2% of the patients within a home palliative
      care center in the first year of legalization. Patient demographics were
      consistent with those documented elsewhere. The TLCPC process accommodates the
      diverse viewpoints of clinicians and emphasizes continuity of palliative care
      provision.

PMID- 30095329
TI  - Role of Computationally Evaluated Target Specificity in the Hepatotoxicity of
      Gapmer Antisense Oligonucleotides.
AB  - Gapmer antisense oligonucleotides (gapmers) sometimes cleave nontarget pre-mRNAs
      by recognizing target-like intronic/exonic portions. This off-target RNA cleavage
      could be a major cause of the hepatotoxicity that is induced by gapmers. In line
      with these findings, we hypothesized that gapmers with higher specificity have
      less hepatotoxicity, and that those with lower specificity have greater toxicity.
      To examine this concept, we investigated various Malat1-targeting gapmers with
      various computationally evaluated target specificities. We had expected that
      higher specificity gapmers would have lower hepatotoxicity, but these factors
      were not significantly related. In silico analysis of gapmer sequences does not
      always contribute to mitigating the risk of hepatotoxicity. Transcriptome
      analysis indicated that nontoxic gapmers do not cleave off-target RNAs, although
      they have many target-like RNA sequences. The present results shed light on the
      mechanism of the hepatotoxicity of gapmers.

PMID- 30095330
TI  - Stochastic optimization of adaptive enrichment designs for two subpopulations.
AB  - An adaptive enrichment design is a randomized trial that allows enrollment
      criteria to be modified at interim analyses, based on a preset decision rule.
      When there is prior uncertainty regarding treatment effect heterogeneity, these
      trial designs can provide improved power for detecting treatment effects in
      subpopulations. We present a simulated annealing approach to search over the
      space of decision rules and other parameters for an adaptive enrichment design.
      The goal is to minimize the expected number enrolled or expected duration, while
      preserving the appropriate power and Type I error rate. We also explore the
      benefits of parallel computation in the context of this goal. We find that
      optimized designs can be substantially more efficient than simpler designs using
      Pocock or O'Brien-Fleming boundaries.

PMID- 30095332
TI  - Letter to the Editor. Barriers to global surgery academic collaborations.

PMID- 30095331
TI  - Risk factors for latent tuberculosis infection in children in South Korea.
AB  - OBJECTIVES: In South Korea, latent tuberculosis infection (LTBI) screening is a
      critical strategy associated with efforts to reduce the incidence of tuberculosis
      (TB). Currently, only children with a known history of TB contact are considered
      as pediatric high-risk groups for LTBI, and consequently, LTBI screening is only
      provided to these children. However, to reduce the incidence of TB, the high-risk
      groups that undergo LTBI screening should be expanded. This study aimed to assess
      the risk factors for LTBI among children living in South Korea with no known
      history of TB contact for the identification of additional high-risk groups. We
      investigated the risk factors for LTBI among US visa applicant children, who
      undergo LTBI screening regardless of their TB contact history. METHODS: We
      obtained data on demographic characteristics, medical history, Bacillus Calmette
      Guerin (BCG) vaccination history, and results of LTBI screening for children aged
      2-14 years. A tuberculin skin test was used for the diagnosis of LTBI, and an
      induration of 10 mm or greater was used to define a positive test. Adjusted odds
      ratios and 95% confidence intervals were calculated to determine the association
      between clinical and demographic variables and LTBI. RESULTS: Of the 1,664 study
      participants, 91 (5.5%) had LTBI. The binary logistic regression analysis showed
      that children born in high TB burden foreign countries had the highest odds of
      LTBI when considering all the risk factors investigated. Increasing age, absence
      of BCG vaccination, and a previous diagnosis of asthma were also significant risk
      factors for LTBI. CONCLUSION: These results indicate that children born in high
      TB burden foreign countries should be considered a high-risk group for LTBI in
      South Korea; the inclusion of these children in LTBI screening should be
      considered.

PMID- 30095333
TI  - High-resolution QSM for functional and structural depiction of subthalamic nuclei
      in DBS presurgical mapping.
AB  - OBJECTIVE Faithful depiction of the subthalamic nucleus (STN) is critical for
      planning deep brain stimulation (DBS) surgery in patients with Parkinson's
      disease (PD). Quantitative susceptibility mapping (QSM) has been shown to be
      superior to traditional T2-weighted spin echo imaging (T2w). The aim of the study
      was to describe submillimeter QSM for preoperative imaging of the STN in planning
      of DBS. METHODS Seven healthy volunteers were included in this study. T2w and QSM
      were obtained for all healthy volunteers, and images of different resolutions
      were reconstructed. Image quality and visibility of STN anatomical features were
      analyzed by a radiologist using a 5-point scale, and contrast properties of the
      STN and surrounding tissue were calculated. Additionally, data from 10
      retrospectively and randomly selected PD patients who underwent 3-T MRI for DBS
      were analyzed for STN size and susceptibility gradient measurements. RESULTS
      Higher contrast-to-noise ratio (CNR) values were observed in both high-resolution
      and low-resolution QSM images. Inter-resolution comparison demonstrated
      improvement in CNR for QSM, but not for T2w images. QSM provided higher inter
      quadrant contrast ratios (CR) within the STN, and depicted a gradient in the
      distribution of susceptibility sources not visible in T2w images. CONCLUSIONS For
      3-T MRI, submillimeter QSM provides accurate delineation of the functional and
      anatomical STN features for DBS targeting.

PMID- 30095334
TI  - Nervus intermedius and the surgical management of geniculate neuralgia.
AB  - OBJECTIVE Geniculate neuralgia (GN) is an uncommon craniofacial pain syndrome
      attributable to nervus intermedius (NI) dysfunction. Diagnosis and treatment can
      be challenging, due to the complex nature of ear sensory innervation, resulting
      in clinical overlap with trigeminal neuralgia (TN) and glossopharyngeal neuralgia
      (GPN). METHODS A retrospective review of a prospective neurosurgical database at
      our institution was performed, 2000-2017, with a corresponding systematic
      literature review. Pain outcomes were dichotomized as unfavorable for
      unchanged/worsened symptoms versus favorable if improved/resolved. Eight formalin
      fixed brains were examined to describe NI at the brainstem. RESULTS Eleven
      patients were surgically treated for GN-9 primary, 2 reoperations. The median age
      was 48, 7 patients were female, and the median follow-up was 11 months (range 3
      143). Seven had >= 2 probable cranial neuralgias. NI was sectioned in 9 and
      treated via microvascular decompression (MVD) in 2. Five patients underwent
      simultaneous treatment for TN (4 MVD; 1 rhizotomy) and 5 for GPN (3 MVD; 2
      rhizotomy). Eleven reported symptomatic improvement (100%); 8 initially reported
      complete resolution (73%). Pain outcomes at last contact were favorable in 8
      (73%)-all among the 9 primary operations (89% vs 0%, p = 0.054). Six prior series
      reported outcomes in 111 patients. CONCLUSIONS GN is rare, and diagnosis is
      confounded by symptomatic overlap with TN/GPN. Directed treatment of all possible
      neuralgias improved pain control in almost all primary operations. Repeat surgery
      seems a risk factor for an unfavorable outcome. NI is adherent to superomedial
      VIII at the brainstem; the intermediate/cisternal portion is optimal for
      visualization and sectioning.

PMID- 30095335
TI  - Differences between patient- and professional-reported modified Rankin Scale
      score in patients with unruptured aneurysms.
AB  - OBJECTIVE Clinical trials forming the basis of current guidelines for the
      management of intracranial aneurysms have relied on patient-reported modified
      Rankin Scale (mRS) scores to assess functional outcome. The effect of patient
      demographics on perception of disability and, by extension, patient-reported mRS
      score, is not well understood. METHODS A consecutive series of patients with a
      previously treated or untreated unruptured intracranial aneurysm (UIA)
      prospectively underwent a structured interview with a trained nurse. At the
      conclusion of this interview, the patients were assigned an mRS score in
      accordance with their degree of disability. During the same visit, patients were
      also required to grade themselves on a paper sheet containing the mRS and
      corresponding information. Data on patient and aneurysm characteristics were also
      collected during the same visit. Agreement between patient- and nurse-reported
      mRS scores was assessed using Cohen's kappa coefficient. The effect of patient
      demographics on the frequency of higher patient- than nurse-reported mRS scores
      was assessed using the Pearson's chi-square and Fisher's exact tests. RESULTS A
      total of 209 patients with a UIA were included in the study, 38 of whom (18.2%)
      had undergone previous treatment. The majority of patients were female (161/209,
      77.0%), and the mean age of the cohort was 60.2 years (SD 13.7 years). Agreement
      between patient- and nurse-reported mRS scores occurred in 72.7% of cases (95% CI
      66.3%-78.3%), with a kappa coefficient of 0.58 (95% CI 0.49-0.67). Patients
      younger than 75 years were more likely to report a higher mRS score than the
      nurse (19.4% vs 3.4%, p = 0.034). Among female patients, those without a college
      degree were more likely to report a higher mRS score than the nurse (22.5% vs
      9.5%, p = 0.035). CONCLUSIONS The results suggest that patient demographics may
      influence perception of disability. These findings should be considered when
      using patient-reported mRS scores to determine functional outcome.

PMID- 30095336
TI  - Induction of aneurysmogenic high positive wall shear stress gradient by wide
      angle at cerebral bifurcations, independent of flow rate.
AB  - OBJECTIVE Endothelium adapts to wall shear stress (WSS) and is functionally
      sensitive to positive (aneurysmogenic) and negative (protective) spatial WSS
      gradients (WSSG) in regions of accelerating and decelerating flow, respectively.
      Positive WSSG causes endothelial migration, apoptosis, and aneurysmal
      extracellular remodeling. Given the association of wide branching angles with
      aneurysm presence, the authors evaluated the effect of bifurcation geometry on
      local apical hemodynamics. METHODS Computational fluid dynamics simulations were
      performed on parametric bifurcation models with increasing angles having: 1)
      symmetrical geometry (bifurcation angle 60 degrees -180 degrees ), 2)
      asymmetrical geometry (daughter angles 30 degrees /60 degrees  and 30 degrees /90
      degrees ), and 3) curved parent vessel (bifurcation angles 60 degrees -120
      degrees ), all at baseline and double flow rate. Time-dependent and time-averaged
      apical WSS and WSSG were analyzed. Results were validated on patient-derived
      models. RESULTS Narrow symmetrical bifurcations are characterized by protective
      negative apical WSSG, with a switch to aneurysmogenic WSSG occurring at angles >=
      85 degrees . Asymmetrical bifurcations develop positive WSSG on the more obtuse
      daughter branch. A curved parent vessel leads to positive apical WSSG on the side
      corresponding to the outer curve. All simulations revealed wider apical area
      coverage by higher WSS and positive WSSG magnitudes, with increased bifurcation
      angle and higher flow rate. Flow rate did not affect the angle threshold of 85
      degrees , past which positive WSSG occurs. In curved models, high flow displaced
      the impingement area away from the apex, in a dynamic fashion and in an angle
      dependent manner. CONCLUSIONS Apical shear forces and spatial gradients are
      highly dependent on bifurcation and inflow vessel geometry. The development of
      aneurysmogenic positive WSSG as a function of angular geometry provides a
      mechanotransductive link for the association of wide bifurcations and aneurysm
      development. These results suggest therapeutic strategies aimed at altering
      underlying unfavorable geometry and deciphering the molecular endothelial
      response to shear gradients in a bid to disrupt the associated aneurysmal
      degeneration.

PMID- 30095337
TI  - The efficacy and limits of magnetic resonance-guided focused ultrasound
      pallidotomy for Parkinson's disease: a Phase I clinical trial.
AB  - OBJECTIVE Recently, MR-guided focused ultrasound (MRgFUS) has emerged as an
      innovative treatment for numerous neurological disorders, including essential
      tremor, Parkinson's disease (PD), and some psychiatric disorders. Thus, clinical
      applications with this modality have been tried using various targets. The
      purpose of this study was to determine the feasibility, initial effectiveness,
      and potential side effects of unilateral MRgFUS pallidotomy for the treatment of
      parkinsonian dyskinesia. METHODS A prospective, nonrandomized, single-arm
      clinical trial was conducted between December 2013 and May 2016 at a single
      tertiary medical center. Ten patients with medication-refractory, dyskinesia
      dominant PD were enrolled. Participants underwent unilateral MRgFUS pallidotomy
      using the Exablate 4000 device (InSightec) after providing written informed
      consent. Patients were serially evaluated for motor improvement,
      neuropsychological effects, and adverse events according to the 1-year follow-up
      protocol. Primary measures included the changes in the Unified Parkinson's
      Disease Rating Scale (UPDRS) and Unified Dyskinesia Rating Scale (UDysRS) scores
      from baseline to 1 week, 1 month, 3 months, 6 months, and 1 year. Secondary
      measures consisted of neuropsychological batteries and quality of life
      questionnaire (SF-36). Technical failure and safety issues were also carefully
      assessed by monitoring all events during the study period. RESULTS Unilateral
      MRgFUS pallidotomy was successfully performed in 8 of 10 patients (80%), and
      patients were followed up for more than 6 months. Clinical outcomes showed
      significant improvements of 32.2% in the "medication-off" UPDRS part III score (p
      = 0.018) and 52.7% in UDysRS (p = 0.017) at the 6-month follow-up, as well as
      39.1% (p = 0.046) and 42.7% (p = 0.046) at the 1-year follow-up, respectively.
      These results were accompanied by improvement in quality of life. Among 8 cases,
      1 patient suffered an unusual side effect of sonication; however, no patient
      experienced persistent aftereffects. CONCLUSIONS In the present study, which
      marks the first Phase I pilot study of unilateral MRgFUS pallidotomy for
      parkinsonian dyskinesia, the authors demonstrated the efficacy of pallidal
      lesioning using MRgFUS and certain limitations that are unavoidably associated
      with incomplete thermal lesioning due to technical issues. Further investigation
      and long-term follow-up are necessary to validate the use of MRgFUS in clinical
      practice. Clinical trial registration no.: NCT02003248 (clinicaltrials.gov).

PMID- 30095338
TI  - Noncontrast vestibular schwannoma surveillance imaging including an MR
      cisternographic sequence: is there a need for postcontrast imaging?
AB  - OBJECTIVE The purpose of this study was to evaluate the use of a noncontrast MRI
      protocol that includes a cisternographic sequence (CISS/FIESTA/3D DRIVE) compared
      to a protocol that includes a gadolinium-enhanced sequence in order to determine
      whether a noncontrast approach could be utilized to follow vestibular
      schwannomas. METHODS A total of 251 patients with vestibular schwannomas who
      underwent MRI of the temporal bones that included both cisternographic sequence
      and postcontrast T1 imaging between January 2000 and January 2016 for
      surveillance were included in this retrospective study. The size of the
      vestibular schwannomas was independently assessed on a noncontrast MR
      cisternographic sequence and compared to size measurements on a postcontrast
      sequence. The evaluation of intralesional cystic components (identified as T2
      signal hyperintensity) and hemorrhagic components (identified with intrinsic T1
      hyperintensity) on noncontrast MR sequences was compared to evaluation on
      postcontrast MR sequences to determine whether additional information could be
      derived from the postcontrast sequences. Additionally, any potentially clinically
      significant, incidentally detected findings on the postcontrast T1 sequences were
      documented and compared with the detection of these findings on the precontrast
      images. RESULTS No significant difference in vestibular schwannoma size was found
      when comparing measurements made on the images obtained with the MR
      cisternographic sequence and those made on images obtained with the postcontrast
      sequence (p = 0.99). Noncontrast MR images were better (detection rate of 87%)
      than postcontrast images for detection of cystic components. Noncontrast MR
      images were also better for identifying hemorrhagic components. No additional
      clinically relevant information regarding the tumors was identified on the
      postcontrast sequences. CONCLUSIONS Based on the results of this study, a
      noncontrast MR protocol that includes a cisternographic sequence would be
      sufficient for the accurate characterization of size and signal characteristics
      of vestibular schwannomas, obviating the need for gadolinium contrast
      administration for the routine surveillance of these lesions.

PMID- 30095339
TI  - Giant intracranial aneurysms of the posterior circulation and their relation to
      the brainstem: analysis of risk factors for neurological deficits.
AB  - OBJECTIVE Giant posterior circulation aneurysms (GPCirAs) usually cause
      substantial mass effect on the brainstem, which may lead to neurological
      deficits. So far, there has been no systematic investigation of factors
      associated with such deficits in GPCirA. The authors aim to examine the risk
      factors for cranial nerve deficit (CND), motor deficit, and disability in
      patients with GPCirA. METHODS Using MR images obtained in 30 patients with
      unruptured GPCirA, the authors examined GPCirA volume, presence of hydrocephalus
      or partial thrombosis (PT) of the aneurysm, and the degree of brainstem
      displacement measured by the distance between the McRae line and the tip of the
      GPCirA (?MT). They evaluated associations between these factors and neurological
      deficits. RESULTS Thirty GPCirAs in 30 patients were included. The prevalence of
      CNDs was 50%. Patients with CNDs significantly differed from those without CNDs
      in terms of age (mean 51.0 years [SD 15.0 years] vs 69.0 years [SD 21.0 years], p
      = 0.01) and in ?MT (median 50.7 mm [IQR 39.2-53.9 mm] vs 39.0 mm [IQR 32.3-45.9
      mm], p = 0.02). The prevalence of motor deficits was 33.3%. Patients with motor
      deficits showed a larger ?MT (median 50.5 mm [IQR 40.8-54.6 mm]) compared with
      those without (?MT: median 39.1 mm [IQR 32.8-50.5 mm], p = 0.04). GPCirA volume
      was larger in patients with poor modified Rankin Scale (mRS) scores (median 14.9
      cm3 [IQR 8.6-18.7 cm3]) than in those with mRS scores of 0-2 (median 6.8 cm3 [IQR
      4.4-11.7 cm3], p = 0.03). After adjusting for patient age and the occurrence of
      hydrocephalus or PT, the authors found that higher degrees of disability were
      significantly associated with aneurysm volume (OR 1.13, 95% CI 1.0-1.3; p =
      0.04), but not with ?MT. The occurrence of CND or motor deficit was not
      associated with any of the examined variables. There was no correlation between
      GPCirA volume and ?MT (rs = 0.01, p = 0.96). The prevalence of neurological
      deficits did not differ between GPCirA at the basilar apex, the basilar trunk,
      the vertebrobasilar junction, or the vertebral artery. CONCLUSIONS In this study,
      the neurological condition of the patients was associated only with GPCirA volume
      and not with the degree of brainstem displacement, the occurrence of PT or
      hydrocephalus, or the exact location of the GPCirA. These findings highlight the
      clinical relevance of GPCirA volume and suggest that factors such as brainstem
      displacement or PT should play less of a role when finding arguments for or
      against treatment of GPCirA. Clinical trial registration no.: NCT02066493
      (clinicaltrials.gov).

PMID- 30095341
TI  - Letter to the Editor. MRI and trigeminal neuralgia.

PMID- 30095340
TI  - Evaluation of the extent of resection and detection of ischemic lesions with
      intraoperative MRI in glioma surgery: is intraoperative MRI superior to early
      postoperative MRI?
AB  - OBJECTIVE MRI scans obtained within 48-72 hours (early postoperative MRI
      [epMRI]), prior to any postoperative reactive changes, are recommended for the
      accurate assessment of the extent of resection (EOR) after glioma surgery.
      Diffusion-weighted imaging (DWI) enables ischemic lesions to be detected and
      distinguished from the residual tumor. Prior studies, however, revealed that
      postoperative reactive changes were often present, even in epMRI. Although
      intraoperative MRI (iMRI) is widely used to maximize safe resection during glioma
      surgery, it is unclear whether iMRI is superior to epMRI when evaluating the EOR,
      because it theoretically shows fewer postoperative reactive changes. In addition,
      the ability to detect ischemic lesions using iMRI has not been investigated.
      METHODS The authors retrospectively analyzed prospectively collected data in 30
      patients with glioma (22 and 8 patients with enhancing and nonenhancing lesions,
      respectively) who underwent tumor resection. These patients had received
      preoperative MRI within 24 hours prior to surgery, postresection radiological
      evaluation with iMRI during surgery, and epMRI within 24 hours after surgery,
      with all neuroimaging performed using identical 1.5T MRI scanners. The authors
      compared iMRI or epMRI with preoperative MRI, and defined a postoperative
      reactive change as a new postoperative enhancement or T2 high-intensity area
      (HIA), if this lesion was outside of the preoperative original tumor location. In
      addition, postoperative ischemia was evaluated on DWI. The iMRI and epMRI
      findings were compared in terms of 1) postoperative reactive changes, 2)
      evaluation of the EOR, and 3) presence of ischemic lesion on DWI. RESULTS In
      patients with enhancing lesions, a new enhancement was seen in 8 of 22 patients
      (36.4%) on iMRI and in 12 of 22 patients (54.5%) on epMRI. In patients with
      nonenhancing lesions, a new T2 HIA was seen in 4 of 8 patients (50.0%) on iMRI
      and in 7 of 8 patients (87.5%) on epMRI. A discrepancy between the EOR measured
      on iMRI and epMRI was noted in 5 of the 22 patients (22.7%) with enhancing
      lesions, and in 3 of the 8 patients (37.5%) with nonenhancing lesions. The
      occurrence of ischemic lesions on DWI was found in 5 of 30 patients (16.7%) on
      iMRI, whereas it was found in 16 of 30 patients (53.3%) on epMRI (p = 0.003);
      ischemic lesions were underestimated on iMRI in 11 patients. CONCLUSIONS Overall,
      given the lower incidence of postoperative reactive changes on iMRI, it was
      superior to epMRI in evaluating the EOR in patients with glioma, both with
      enhancing and nonenhancing lesions. However, because ischemic lesions can be
      overlooked on iMRI, the authors recommend only the additional DWI scan during the
      early postoperative period. Clinicians need to be mindful about not
      overestimating the presence of residual tumor on epMRI due to the high incidence
      of postoperative reactive changes.

PMID- 30095342
TI  - Letter to the Editor. Brain invasion and the risk for postoperative hemorrhage
      and neurological deterioration after meningioma surgery.

PMID- 30095344
TI  - Hippocampal transection for stereo-electroencephalography-proven dominant mesial
      temporal lobe epilepsy in a child: a detailed case report and critical review.
AB  - Resection of the hippocampus ipsilateral to the verbal memory-dominant hemisphere
      frequently results in severe memory deficits. In adults with epilepsy, multiple
      hippocampal transections (MHTs) have resulted in excellent seizure outcome with
      preservation of verbal memory. The authors report the first detailed case of a
      child undergoing MHTs for mesial temporal lobe epilepsy. A 13-year-old right
      handed boy had intractable seizures characterized by epigastric discomfort
      evolving to unresponsiveness and chewing automatisms, lasting 1 minute and
      occurring 2-3 times weekly, sometimes ending in a generalized tonic-clonic
      seizure. He had no seizure risk factors and nonfocal examination results.
      Interictal electroencephalography (EEG) showed frequent left temporal
      epileptiform discharges (maximum FT9) and intermittent slowing. Video EEG, FDG
      PET, and 1.5-T MRI were nonlocalizing. Neuropsychological evaluation suggested
      left temporal lobe dysfunction. A stereo-EEG investigation using 8 electrodes
      localized the seizure onset zone to the anterior mesial temporal region,
      immediately involving the hippocampus. The temporal pole and amygdala were
      resected en bloc with 3 MHTs. Comparison of neuropsychological tests 4 months
      before and 6 months after the surgery showed a significant decline only in
      confrontational naming and no significant change in verbal memory. Six and a half
      years later, the patient remains seizure free with no antiepileptic drugs. In
      children with established hemispheric dominance suffering from mesial temporal
      lobe epilepsy, MHTs may be an option.

PMID- 30095343
TI  - Surgeon specialty and patient outcomes in carotid endarterectomy.
AB  - OBJECTIVE The goal of this study was to compare outcomes of carotid
      endarterectomy performed by neurological, general, and vascular surgeons. METHODS
      The authors identified 80,475 patients who underwent carotid endarterectomy
      between 2006 and 2015 in the National Surgical Quality Improvement Program, a
      prospectively collected, national clinical database with established
      reproducibility and validity. Nine hundred forty-three patients were operated on
      by a neurosurgeon; 75,649 by a vascular surgeon; and 3734 by a general surgeon.
      Preoperative and intraoperative characteristics and 30-day outcomes were
      stratified by the surgeon's primary specialty. Using propensity scores,
      comprising pre- and intraoperative characteristics as well as procedure and
      diagnostic codes, the authors matched 203 neurosurgery (NS) patients to 203
      vascular surgery (VS) patients and 203 NS patients to 203 general surgery (GS)
      patients. No pre- or intraoperative factors were significantly different between
      specialties in the matched sample. Regular logistic regression and conditional
      logistic regression were used to predict postoperative complications in the full
      sample and in the matched sample. RESULTS In the complete population sample, NS
      patients, when compared to patients of general and vascular surgeons, were less
      likely to be admitted from home and more likely to have carotid artery occlusion
      or stenosis with cerebral infarction, to be a current smoker, to have had recent
      chemo- or radiotherapy, to have surgery under general anesthesia, to undergo
      multiple procedures, and to have longer surgery times. In unadjusted analyses, NS
      patients were more likely to experience major complications (NS vs VS: odds ratio
      1.3, 95% CI 1.1-1.6; NS vs GS: odds ratio 1.3, 95% CI 1.0-1.7); minor
      complications (NS vs VS: odds ratio 2.9, 95% CI 2.0-4.1; NS vs GS: odds ratio
      2.7, 95% CI 1.7-4.2); intra- or postoperative transfusions (NS vs VS: odds ratio
      1.6, 95% CI 1.4-1.9; NS vs GS: odds ratio 1.9, 95% CI 1.6-2.3); prolonged
      hospitalization (NS vs VS: odds ratio 3.0, 95% CI 2.6-3.5; NS vs GS: odds ratio
      2.6, 95% CI 2.2-3.0); and discharge to skilled care facilities (NS vs VS: odds
      ratio 2.8, 95% CI 2.3-3.4; NS vs GS: odds ratio 3.1, 95% CI 2.4-4.1). In
      adjusted, propensity-matched analyses, however, patients' outcome with carotid
      endarterectomy performed by NS was comparable with those completed by GS and VS.
      CONCLUSIONS Patients who undergo carotid endarterectomy performed by a
      neurosurgeon tend to have a greater preoperative disease burden than do those
      treated by a general or vascular surgeon, which contributes significantly to more
      morbid postoperative courses. In patients matched carefully on the basis of
      health status at the time of surgery and intraoperative variables that affect
      results, patients' outcomes after carotid endarterectomy do not appear to depend
      on the attending surgeon's primary specialty.

PMID- 30095345
TI  - Divergence insufficiency alleviated by posterior fossa decompression with
      duraplasty in a patient with Chiari type 1.5 malformation.
AB  - The authors present a case of Chiari type 1.5 malformation with the uncommon
      presenting symptoms of esotropia and diplopia due to divergence insufficiency in
      a 12-year-old girl. Imaging at initial diagnosis revealed cerebellar herniation
      with extension of the tonsils to the C2 vertebral body, a retroflexed odontoid,
      and a small cervical syrinx. The patient was initially treated with an
      uncomplicated Chiari malformation decompression without dural opening. Repeat
      imaging revealed an adequate decompression. Three months postoperatively the
      patient's diplopia recurred and she underwent repeat posterior fossa
      decompression with dural opening and duraplasty. Following repeat decompression
      with dural opening and duraplasty, the patient's diplopia had not recurred by the
      2-year follow-up. https://thejns.org/doi/abs/10.3171/2018.5.PEDS1886.

PMID- 30095346
TI  - Currarino syndrome: repair of the dysraphic anomalies and resection of the
      presacral mass in a combined neurosurgical and general surgical approach.
AB  - OBJECTIVE It is well established that Currarino syndrome (CS) may be associated
      with spinal dysraphism. Here, the authors report on 10 CS patients with dysraphic
      anomalies who had undergone a combined neurosurgical and general surgical
      approach to repair the dysraphic anomalies and resect the presacral mass in a
      single operation. They discuss the spectrum of spinal dysraphism that may coexist
      in CS in the context of its developmental etiology. METHODS Children with a
      confirmed CS diagnosis who had undergone the combined operative approach were
      identified from a departmental database. Presenting features were recorded and
      preoperative imaging was analyzed to record features of the presacral mass and
      the dysraphic anomalies. The histopathological nature of the resected presacral
      mass and the outcomes postoperatively and at the last follow-up were reviewed.
      RESULTS Between 2008 and 2015, 10 patients presented with CS, 9 with
      constipation. Median age at the time of surgery was 1.3 years. Six of the 10
      patients had anorectal malformation consisting of anal stenosis, rectal stenosis,
      or imperforate anus. Spinal anomalies included anterior meningocele (5 cases),
      low-lying conus (8), terminal syrinx (4), fatty filum (5), caudal lipoma (3), and
      intraspinal cyst (1). In all cases, the lumbosacral spinal canal was accessed via
      a midline approach with laminoplasty, allowing spinal cord untethering and repair
      of the dysraphic anomalies. Following dural closure, the incision was extended
      inferiorly to incorporate a posterior sagittal approach to resect the presacral
      mass. The histopathological nature of the mass was mature teratoma (8 cases),
      complex hamartomatous malformation (1), or neurenteric cyst (1). There were no
      new instances of neurological deterioration, with most instances of persisting
      morbidity related to constipation (6 cases) or neurogenic bladder dysfunction
      (8). There were no infective complications, no instances of cerebrospinal fluid
      fistula, no recurrences of the presacral mass, and no cases of retethering of the
      spinal cord. CONCLUSIONS Although not part of the original triad, spinal
      dysraphic anomalies are common in CS and in keeping with a disorder of secondary
      neurulation. Lumbosacral MRI is an essential investigation when CS is suspected.
      Children are at risk of sphincter impairment due to the anorectal malformation;
      however, both spinal cord tethering and compression from the presacral mass may
      further compromise long-term continence. A combined operative approach to repair
      the dysraphic anomalies and resect the presacral mass is described with good
      postoperative and long-term outcomes.

PMID- 30095347
TI  - The identification of a subgroup of children with traumatic subarachnoid
      hemorrhage at low risk of neuroworsening.
AB  - OBJECTIVE Pediatric traumatic subarachnoid hemorrhage (tSAH) often results in
      intensive care unit (ICU) admission, the performance of additional diagnostic
      studies, and ICU-level therapeutic interventions to identify and prevent episodes
      of neuroworsening. METHODS Data prospectively collected in an institutionally
      specific trauma registry between 2006 and 2015 were supplemented with a
      retrospective chart review of children admitted with isolated traumatic
      subarachnoid hemorrhage (tSAH) and an admission Glasgow Coma Scale (GCS) score of
      13-15. Risk of blunt cerebrovascular injury (BCVI) was calculated using the BCVI
      clinical prediction score. RESULTS Three hundred seventeen of 10,395 pediatric
      trauma patients were admitted with tSAH. Of the 317 patients with tSAH, 51
      children (16%, 23 female, 28 male) were identified with isolated tSAH without
      midline shift on neuroimaging and a GCS score of 13-15 at presentation. The
      median patient age was 4 years (range 18 days to 15 years). Seven had modified
      Fisher grade 3 tSAH; the remainder had grade 1 tSAH. Twenty-six patients (51%)
      had associated skull fractures; 4 involved the petrous temporal bone and 1 the
      carotid canal. Thirty-nine (76.5%) were admitted to the ICU and 12 (23.5%) to the
      surgical ward. Four had an elevated BCVI score. Eight underwent CT angiography;
      no vascular injuries were identified. Nine patients received an imaging
      associated general anesthetic. Five received hypertonic saline in the ICU.
      Patients with a modified Fisher grade 1 tSAH had a significantly shorter ICU stay
      as compared to modified Fisher grade 3 tSAH (1.1 vs 2.5 days, p = 0.029).
      Neuroworsening was not observed in any child. CONCLUSIONS Children with isolated
      tSAH without midline shift and a GCS score of 13-15 at presentation appear to
      have minimal risk of neuroworsening despite the findings in some children of
      skull fractures, elevated modified Fisher grade, and elevated BCVI score. In this
      subgroup of children with tSAH, routine ICU-level care and additional diagnostic
      imaging may not be necessary for all patients. Children with modified Fisher
      grade 1 tSAH may be particularly unlikely to require ICU-level admission.
      Benefits to identifying a subgroup of children at low risk of neuroworsening
      include improvement in healthcare efficiency as well as decreased utilization of
      unnecessary and potentially morbid interventions, including exposure to ionizing
      radiation and general anesthesia.

PMID- 30095348
TI  - Intraventricular bone dust migration after neuroendoscopy: report of 2 cases.
AB  - Neuroendoscopy has demonstrated safety and efficacy in the treatment of a host of
      pediatric neurosurgical pathologies. With the increase in its applicability,
      several associated complications have been described in the literature. A common
      practice in pediatric neurosurgery is the use of Gelfoam sponge pledget in the
      burr hole, followed by bone fragments and dust (obtained from the created burr
      hole), to cover the dural defect. This technique is used to enhance burr hole
      sealing and potentially prevent CSF leakage from the surgical site. Reports on
      intracranial bone dust migration associated with this technique are scarce. The
      authors report 2 cases of intracranial migration of bone fragments after an
      endoscopic third ventriculostomy and an endoscopic colloid cyst resection. The
      bone fragment migration was thought to be caused by negative pressure from a
      lumbar puncture in one case and external trauma to the head in the other. As
      endoscopy becomes more widely used, it is important to be aware of this potential
      complication that may in some cases require an intervention. A review of the
      cases reported in the literature is provided and a technique is suggested to help
      prevent this complication.

PMID- 30095349
TI  - [Multilingual children and language impairment].
AB  - Multilingual children and language impairment Abstract. For many children with a
      migration background, difficulties acquiring their second language skills
      influences their educational success. Because of the wide range of languages and
      their varieties, which are not described linguistically in detail, development of
      reliable and valid assessment procedures is hindered. This results in a
      diagnostic dilemma, as children who have problems learning their second language,
      along with many other reasons, have to be distinguished from children suffering
      from a specific language impairment (SLI). Children with migration background may
      show linguistic profiles which superficially resemble those of children with SLI.
      The current paper constitutes a selective review of relevant literature and
      offers suggestions for meeting those respective challenges. It is assumed that
      the prevalence for clinically relevant language disorder is the same in
      multilingual as in monolingual children. Also, multilingual children like
      monolingual children can show subtle cognitive weaknesses. The relevance of
      language disorder in psychiatrically ill multilingual and monolingual children is
      well known and has to be considered in the context of a comprehensive assessment.
      For those children with a migration background who face more pronounced problems
      acquiring their second language skills, language assessment in their mother
      tongue is essential.

PMID- 30095350
TI  - Antithrombotic strategies after interventional left atrial appendage closure: an
      update.
AB  - INTRODUCTION: Interventional left atrial appendage occlusion (LAAO) has emerged
      as a valid alternative to oral anticoagulation (OAC) therapy for the prevention
      of ischemic stroke and systemic embolism in patients with non-valvular atrial
      fibrillation (AF). Areas covered: Antithrombotic therapy following interventional
      LAAO is critical in balancing the risk of thromboembolism and bleeding during the
      endothelialization of the implanted devices. In this article, the most recent
      clinical trials are reviewed and the current real-world antithrombotic strategies
      following LAAO device implantation are discussed. Expert commentary: For patients
      eligible for OAC and receiving a Watchman device, the most solid scientific
      evidence exists for warfarin plus aspirin for 45 days followed by dual
      antiplatelet therapy (DAPT) for 6 months and a lifelong aspirin therapy. In real
      world most patients are being treated with DAPT for 3-6 months. Alternatively,
      the Watchman was approved for 3 months of novel OAC (NOAC) therapy in conjunction
      with aspirin. For all other devices, DAPT for 1-6 months has been used in the
      vast majority of cases. Considering major bleeding as the predominant
      complication following LAAO, evidence suggests that short-term DAPT (6 weeks) or
      single antiplatelet therapy using aspirin may be a viable option.

PMID- 30095351
TI  - The Exposome: Molecules to Populations.
AB  - Derived from the term exposure, the exposome is an omic-scale characterization of
      the nongenetic drivers of health and disease. With the genome, it defines the
      phenome of an individual. The measurement of complex environmental factors that
      exert pressure on our health has not kept pace with genomics and historically has
      not provided a similar level of resolution. Emerging technologies make it
      possible to obtain detailed information on drugs, toxicants, pollutants,
      nutrients, and physical and psychological stressors on an omic scale. These
      forces can also be assessed at systems and network levels, providing a framework
      for advances in pharmacology and toxicology. The exposome paradigm can improve
      the analysis of drug interactions and detection of adverse effects of drugs and
      toxicants and provide data on biological responses to exposures. The
      comprehensive model can provide data at the individual level for precision
      medicine, group level for clinical trials, and population level for public
      health. Expected final online publication date for the Annual Review of
      Pharmacology and Toxicology Volume 59 is January 6, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30095353
TI  - Eyes on New Product Development.

PMID- 30095352
TI  - Antimicrobial Activity of a New Aloe Vera Formulation for the Hygiene of the
      Periocular Area.
AB  - PURPOSE: The aim of this study was to evaluate the antimicrobial activity of a
      novel preservative-free lid wipe formulation containing Aloe vera gel and
      hyaluronic acid that is commercialized for the hygiene of the periocular area.
      METHODS: In vitro susceptibility testing of the solution contained in wipes
      against bacteria and fungi commonly colonizing the periocular area, both
      reference strains and multidrug-resistant (MDR) clinical isolates, was assessed
      following the CLSI M07-A9 and M27-A3 broth methods, respectively. The solution
      was 2-fold serially diluted in broth from 25 MUL (25% v/v) to 0.012 MUL (0.012%
      v/v) in microtiter plates. Plates were incubated and minimal inhibitory
      concentrations (MICs) were read visually. The antimicrobial effectiveness test
      was performed by inoculating the wipe solution with microbial suspensions at the
      initial concentration of 105-106 CFU/mL, as recommended by the international
      Pharmacopoeias. At different time intervals, samples were tested for microbial
      count. RESULTS: The MIC value of the solution ranged from 25% to 12.5% for
      bacteria and was 6.25% for Candida albicans. The MIC for MDR isolates was 12.5%.
      By assessing antimicrobial effectiveness, we found that the solution meets the
      criteria reported by the European Pharmacopoeia and United States Pharmacopeia
      for its preservative effect. CONCLUSIONS: This study demonstrates that the novel
      wipes herein tested possess antimicrobial activity against bacteria and yeast
      commonly found in the periocular area, and against MDR clinical isolates. The
      microbial death curves obtained following deliberate contamination of the wipe
      solution revealed potent bactericidal and fungicidal activity of the formulation.

PMID- 30095354
TI  - Effects of Botulinum Toxin A Injection on Ambulation Capacity in Patients with
      Cerebral Palsy.
AB  - PURPOSE: The purpose of the study is to assess the change in their ambulatory
      capacity and spasticity in children with cerebral palsy (CP) who received
      botulinum toxin A (BoNT-A) injection and underwent rehabilitation therapy.
      METHODS: Thirty patients with CP, 3-13 years who had varied functional levels and
      lower extremity spasticity, were randomized in two groups. In Group 1(n = 15),
      BoNT-A was administered to the affected extremity and underwent rehabilitation.
      In Group 2 (n = 15), the patients underwent only rehabilitation protocol. The
      Visual Analogue Scale (VAS), Tardieu Scale (TS), Gross Motor Function
      Classification System (GMFCS), Selective Motor Control, and Goal Attainment Scale
      were evaluated 4 and 12 weeks after baseline. RESULTS: The mean scores of the TS
      (p < 0.001) GMFCS, GAS, and VAS (p < 0.05) significantly improved in Group 1.
      CONCLUSION: We think that implementation of rehabilitation protocols with BoNT-A
      injection is superior to alone rehabilitation therapy and increasing ambulatory
      capacity in patients with CP.

PMID- 30095355
TI  - The development and internal consistency of the comprehensive lower limb amputee
      socket survey in active lower limb amputees.
AB  - BACKGROUND: Prosthetic socket fit is an important element associated with
      successful ambulation and use of a prosthesis. Prosthetists and rehabilitation
      clinicians would benefit from an assessment tool that discriminates between and
      quantifies the multiple determinants that influence the lower limb amputee's
      performance and satisfaction of a prosthetic socket. OBJECTIVES: To determine the
      internal consistency of the comprehensive lower limb amputee socket survey, a new
      self-report measure of prosthetic socket satisfaction that quantifies suspension,
      stability, comfort, and appearance. STUDY DESIGN: Cross-sectional sample of
      active amputees. METHODS: Interviews were conducted with prosthetists, physical
      therapists, and lower limb amputees to identify clinical concerns and common
      activities influencing socket fit. An expert panel of five clinicians reviewed
      the items and constructed the original version of the comprehensive lower limb
      amputee socket survey which was then administered to a convenience sample of 47
      active lower limb amputees. Item analysis and Cronbach's alpha were used to
      determine the final version of the comprehensive lower limb amputee socket
      survey. RESULTS: Following item raw score-to-total score correlation with
      Cronbach's alpha for comprehensive lower limb amputee socket survey determinants,
      internal consistency improved when nine questions were eliminated. CONCLUSION:
      The comprehensive lower limb amputee socket survey is a self-report measure of
      prosthetic socket satisfaction with very good internal consistency. Clinical
      relevance When socket problems occur, the ability to determine the specific cause
      can reduce modification time, enhance socket fit, and promote patient
      satisfaction. A standardized multi-dimensional assessment measure of socket
      satisfaction enables prosthetists to quantify the multiple determinants of socket
      satisfaction, improve patient communication, and demonstrate the value of socket
      interventions.

PMID- 30095356
TI  - Response to Novack re: "Pharmacokinetic Analysis of Intraocular Penetration of
      Latanoprost Solutions with Different Preservatives in Human Eyes".

PMID- 30095357
TI  - Considerations for Pursuing Multiple Session Forensic Interviews in Child Sexual
      Abuse Investigations.
AB  - Multiple session forensic interviews (MSFI) are a useful tool in the field of
      child sexual abuse forensic interviewing given the complexity of disclosures and
      the variety of child-centered needs observed in practice. This paper focuses on
      the Children's Advocacy Centers of Texas (CACTX) model for conducting MSFIs,
      illustrated by a description of the statewide training models offered to member
      centers and enumeration of the MSFI protocol guidelines implemented by one
      center. A brief history and review of the single session forensic interview
      (SSFI) is provided followed by considerations for MSFIs in order to establish the
      development of current and new practices. Clarification of terms are outlined
      with examples of cases to distinguish between multiple sessions and subsequent
      sessions. The MSFI guidelines presented demonstrate how an MSFI can fit with the
      SSFI model.

PMID- 30095358
TI  - Mobility in persons with lower extremity amputations and influencing factors:
      Using the International Classification of Functioning, Disability and Health to
      quantify expert views.
AB  - BACKGROUND: International Classification of Function, Health and Disability
      provides a common framework and universal language for rehabilitation
      professionals across the globe. OBJECTIVES: To identify problems in functioning
      and mobility relevant to persons with lower-limb amputation from an expert's
      point of view and quantify these problems using the International Classification
      of Function, Health and Disability. STUDY DESIGN: Qualitative study using
      electronic and paper surveys. METHODS: Electronic or paper survey was done across
      six countries targeting clinicians involved in pre- and post-amputation care.
      Meaningful concepts were extracted from the responses and linked to suitable
      second-level and where applicable third-level International Classification of
      Function, Health and Disability categories. Categorical frequency analysis was
      completed for the combined data and for each location. RESULTS: A total of 183
      experts from 6 different countries responded to the survey. A total of 2171
      concepts were identified, 82% of which could be linked to a second-level
      International Classification of Function, Health and Disability category. The
      categorical frequency analysis revealed that the categories of walking, design
      and construction of buildings for public and private use and sensation of pain
      were the most frequently occurring concepts and was similar across the six
      countries. CONCLUSION: The International Classification of Function, Health and
      Disability can be utilised as a common framework for communication among
      clinicians involved in rehabilitation of persons with lower-limb amputation
      across the globe. The most important factors that were identified by experts in
      amputee rehabilitation working in different international locations were similar.
      Clinical relevance The challenges faced by the clinicians involved in care of
      persons with lower extremity amputation vary across different parts of the world.
      The overarching goal for the clinician irrespective of the location is to improve
      mobility and quality of life of their clients. The International Classification
      of Function, Health and Disability provides a common language between the various
      stakeholders in amputee rehabilitation across the globe.

PMID- 30095359
TI  - Atypical maternal cradling laterality in an impoverished South African
      population.
AB  - Human studies consistently report a 60%-80% maternal left cradling preference.
      The dominant explanation points to an engagement of the emotionally more-attuned
      right brain. In contrast, we found equal incidences of left (31.3%), right
      (34.3%) and no-preference (34.3%) cradling in an impoverished South African
      population living under adverse conditions characterized by extreme dangers. We
      found striking differences on the Parenting Stress Index (PSI) between mothers
      with no cradling laterality preference and mothers with either a left or right
      preference. In several mammals a homologous left preference becomes stronger when
      acute threats prevail, rendering the rightwards shift we observed under dangerous
      conditions seemingly paradoxical. We propose this paradox can be resolved in
      terms of life-history strategy theory which predicts reduced parental investment
      in chronically dangerous environments. We interpret our high PSI score findings
      in no-preference cradlers as indicative of poorer, or at least ambivalent,
      maternal coping which many studies show is typically associated with reduced
      emotional sensitivity and responsiveness. We suggest that the latter may be a
      psychological mechanism mediating a partial withdrawal of parental investment in
      response to an enduringly adverse environment. To the best of our knowledge, this
      is the first study investigating cradling laterality preferences in an adverse
      socioeconomic environment.

PMID- 30095360
TI  - Cardioplegia practice in paediatric cardiac surgery: a UK & Ireland survey.
AB  - INTRODUCTION: Many techniques are available for cardioplegic arrest in children,
      but there is a lack of late phase clinical trials to guide practice. We surveyed
      paediatric cardiac surgeons and perfusionists to establish current practice and
      willingness to change within a clinical trial. METHODS: An online survey was sent
      to all consultant paediatric cardiac surgeons and chief perfusionists in
      paediatric centres in the UK and Ireland. Information was sought on cardioplegia
      type, composition, temperature, topical cooling, dosing for induction and
      maintenance, interval between doses, whether practice changed with patient age or
      complexity and whether respondents would be willing and able to use different
      cardioplegia solutions within a randomised trial. RESULTS: Responses were
      obtained from 32 (78.0%) surgeons and 12 (100%) perfusionists. Twenty-seven
      (84.4%) surgeons use blood cardioplegia in infants, with St. Thomas' Harefield
      preparation the most popular (19, 59.4%), used routinely in eight (66.7%)
      centres. Twenty-two (68.8%) administer at 4-6 degrees C, 18 (56.3%) use topical
      cooling, 18 (56.3%) give 30 ml/kg induction and 15 ml/kg maintenance, with 23
      (71.9%) re-dosing every 20-25 minutes. Thirty (93.8%) surgeons were open to
      randomising patients in a trial, with del Nido (29, 90.6%) the most popular.
      CONCLUSIONS: This survey demonstrates heterogeneity in cardioplegia practice.
      Whilst most surgeons use blood cardioplegia, there is variation in type,
      temperature, topical cooling, dosing and intervals. Combined with a lack of
      evidence from late phase trials, our findings support the presence of clinical
      equipoise. Surgeons are willing to change practice, suggesting that a pragmatic,
      multi-centre, randomised, controlled trial of cardioplegia in children is
      feasible.

PMID- 30095361
TI  - Assisting Caregivers with Frail Elderly in Alleviating Financial Hardships.
AB  - Many caregivers of individuals who are frail and elderly face financial hardships
      that have negative consequences that compound over time. This article explores
      the causes of these hardships, reviews Medicaid home and community-based
      interventions, and related government financial supports that have been used to
      alleviate them and concludes with recommendations for social work practice and
      social policy.

PMID- 30095363
TI  - Laboratory comparison of new high flow rate respirable size-selective sampler.
AB  - A newly developed high flow rate respirable size-selective cyclone sampler
      (GK4.162-also known as the Respirable Air Sampling Cyclone Aluminum Large
      (RASCAL)) was calibrated to determine its optimum operating flow rate. The Health
      and Safety Laboratory in the United Kingdom and two laboratories from the
      National Institute for Occupational Safety and Health in the United States
      conducted experiments using two different methods: (1) polydisperse aerosol and
      time-of-flight direct reading instrument (Aerodynamic Particle Sizer (APS)) and
      (2) monodisperse aerosol and APS. The measured performance data for the cyclone
      was assessed against the international respirable convention using the bias map
      approach. Although the GK4.162 cyclone was tested using different aerosols and
      detection methods, the results from the three laboratories were generally
      similar. The recommended flow rate based on the agreement of results from the
      laboratories was 9.0 L/min.

PMID- 30095364
TI  - Integration of novel hybrid composite discharge electrode with semi-pilot novel
      cross-flow electrostatic precipitator.
AB  - Wet electrostatic precipitators (WESPs) are modern-era pollution control systems
      specifically designed to capture ultrafine particles as well as acid mist, highly
      resistive and sticky particles; however, this requires the use of expensive
      corrosion-resistant metal alloys. The work presented here is part of a continuing
      study at Ohio University aimed at reducing the cost of WESPs by using a novel
      combination of a polymer collector surfaces with a hybrid composite discharge
      electrode. In this study, a hybrid composite discharge electrode was tested, for
      the first time, inside a semi-pilot-scale experimental setup, with collection
      surfaces consists of a vertical array of strands. Particle laden gases were
      passed through this array of polymer ropes, which were kept wet by a small flow
      of water. The discharge electrodes were composite laminates of carbon fibers in a
      polymer matrix enclosing a metal mesh. The preliminary results showed that this
      new integrated system of composite discharge electrode and polymer collector
      surfaces can match or exceed the performance of a conventional metal alloy
      electrostatic precipitator (ESP) with metal discharge electrodes. There are
      additional advantages due to the system being compact, lightweight, and highly
      corrosion resistant. Implications: This study focused on integrating and
      assessing performance of a novel hybrid composite electrode (HCE) inside semi
      pilot novel cross-flow electrostatic precipitator at conditions typically
      observed in coal-fired power plant exhausts. The results were collected for
      particulate collection efficiencies and were compared with a rigid metal
      electrode. The HCE outperformed metal electrode by showing higher particulate
      collection efficiency. This result showcases substantial potential for these two
      new technologies (HCE and cross-flow system) as a substitute for conventional
      metal based wet ESPs.

PMID- 30095362
TI  - Immunogenicity of a Candidate Ebola Hemorrhagic Fever Vaccine in Mice Based on
      Controlled In Vitro Expression of Ebolavirus Glycoprotein.
AB  - Ebolavirus (EBOV) is the etiology of Ebola hemorrhagic fever (EHF). A major EHF
      outbreak in 2014-2015 in West Africa claimed >11,000 lives. A licensed vaccine is
      not available for EHF, although several vaccines have undergone clinical trials.
      We developed a human adenovirus (Ad) serotype 5-based candidate EHF vaccine based
      on controlled expression of the EBOV (Makona strain) glycoprotein (GP) as the
      immunogen. Two clones, AdGP72 and AdGP75, and a control Ad515 vector, were
      generated and tested for protein expression in vitro and immunogenicity in mice.
      Eight groups of mice were immunized with three doses of buffer, Ad515, AdGP72,
      and AdGP75, by two different dose regimens. Three different antigens (AdGP75
      infected Vero E6 cell extract and two baculovirus expressed EBOV GP antigens,
      namely, GP alone or GP with EBOV VP40) were used to evaluate the immune response.
      Expression studies indicated that full-length GP was cleaved into its component
      subunits when expressed in mammalian cells through the Ad vectors. Moreover, in
      coimmunoprecipitation studies, EBOV GP was found to be associated with VP40 when
      expressed in baculoviruses. The candidate vaccines were immunogenic in mice, as
      evaluated by enzyme-linked immunosorbent assay using mammalian- or baculovirus
      derived antigens. Further characterization and development of the candidate
      vaccines are warranted.

PMID- 30095365
TI  - Increased Vitamin B12 Levels in Children with Zinc Deficiency.
AB  - Additional nutritional deficiencies may accompany zinc deficiency. We determined
      the vitamin B12 levels in patients with zinc (Zn) deficiency. This retrospective
      study enrolled 256 patients age 6 months to 16 years (176 females and 80 males)
      in whom Zn levels in hair samples were measured concurrently with serum vitamin
      B12 and ferritin levels. For all patients, we retrospectively assessed the hair
      Zn levels, serum ferritin and vitamin B12 levels, red blood cell count,
      hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin,
      mean corpuscular hemoglobin concentration, and red cell distribution levels. Data
      were analyzed to determine whether there was a significant difference between any
      of these parameters and the presence of vitamin B12 deficiency between patients
      with and without Zn deficiency. In all 118 patients had Zn levels < 100 MUg/g and
      138 patients had levels > 100 MUg/g. No significant differences were observed in
      ferritin levels, red blood cell parameters, or presence of iron deficiency or
      anemia between the two groups (p > 0.05). The median vitamin B12 level was 323
      (range 238-440) pg/mL in the Zn-deficient group and 276 (range 208-382) pg/mL in
      those with normal Zn levels. Vitamin B12 levels were significantly higher in the
      Zn-deficient group (p = 0.02). A significant negative correlation was detected
      between vitamin B12 levels and Zn levels (r = -0.17, p = 0.004). Vitamin B12
      levels are higher in patients with Zn deficiency; thus, Zn may have a negative
      effect on vitamin B12 levels.

PMID- 30095366
TI  - Preparation and reactivation of magnetic biochar by molten salt method: Relevant
      performance for chlorine-containing pesticides abatement.
AB  - Molten salt has been regarded as a versatile and environmental-friendly method
      for the material preparation and waste destruction. In this work, molten FeCl3
      was utilized for the generation of magnetic biochar (MBC) derived from
      simultaneous activation and magnetization of biomass. The sample characterization
      indicated that MBC had a rough surface with BET surface area of 404 m2/g and
      total pore volume of 0.35cm3/g. Highly dispersed Fe3O4 and nitrogen could be
      deposited on the surface, leading to an excellent magnetization property. The MBC
      exhibited a great 2,4-Dichlorophenol (2.4-DCP) and atrazine removal performance
      in solution with the maximum adsorption capacity achieved 298.12 mg/g and 102.17
      mg/g. Kinetics results demonstrated that MBC adsorption met the Pseudo-first
      order model better. Molten NaOH-Na2CO3 was provided for the re-activation of
      exhausted MBC. 2,4-DCP was firstly desorbed from the MBC and subsequently
      destructed by the active species in the melt medium. Chlorine can be captured in
      the molten alkaline medium from the XRD pattern of residues.The MBC could be
      easily recovered with a yield of 98.2% and fixed carbon content of 61.0% after
      the molten salt regeneration process. With no 2,4-DCP detected, 65.5% and 31.69%
      of initial Cl was found in washing water and residues with the molten NaOH
      Na2CO3, respectively. After 4 cycles of regeneration and adsorption, 60.55%
      72.22% of initial adsorption capacity can be kept. This preparation and
      regeneration method can be an effective way to reduce the risk of secondary
      pollution of chlorinated organic compounds during adsorbent regeneration.
      Implications: Molten salt (MS) is a salt or multiple salts with a low melting
      point, and has been applied in many sectors and is regarded as a crucial role in
      terms of energy, environmental, and resource sustainability. In our paper,
      magnetic biochar was prepared by one-step activation and magnetization of fir
      dust using molten FeCl3?6H2O. Meanwhile, a regeneration method using molten
      alkaline salt was provided. Magnetic biochar generated in our study performed
      well in the 2,4-dichlorophenol and atrazine adsorption. After four cycles of
      regeneration and adsorption, 72.2% of initial 2,4-DCP adsorption capacity can be
      kept.

PMID- 30095367
TI  - Autophagy-Src Regulates Connexin43-Mediated Gap Junction Intercellular
      Communication in Irradiated HepG2 Cells.
AB  - Connexin molecules are an important component of the gap junction, with
      connexin43 (Cx43) being the most abundantly expressed type. Src is a nonreceptor
      tyrosine-protein kinase that affects Cx43 activity by multiple mechanisms.
      However, it is not clear how Src regulates Cx43 to influence radiation-induced
      bystander effects (RIBEs). In this study, we demonstrated that Cx43 on Tyr265 was
      phosphorylated by activated Src in alpha-irradiated HepG2 cells, with the total
      expression of Cx43 unchanged. After inhibition of Cx43 phosphorylation in
      irradiated cells, the frequency of gamma-H2AX foci formation in adjacent
      nonirradiated bystander cells was significantly enhanced. Furthermore, this study
      showed that autophagy regulated the activity of Src and phosphorylation of Cx43,
      and the level of autophagy was correlated with the radiation-induced reactive
      oxygen species (ROS). These results suggest that ROS and autophagy play an
      important role in regulating the Src-Cx43 axis to affect the RIBEs. Our findings
      provide new insights into the Cx43-mediated gap junction intercellular
      communication, as well as the underlying mechanism of RIBEs.

PMID- 30095369
TI  - "The Only Thing We Can Do is Treat Them Well Here": Public Health With Latinos in
      a New Immigrant Destination.
AB  - Human service agencies in new immigrant destinations often lack the experience
      and bilingual staff required to provide inguistically and culturally appropriate
      services to Latino immigrant families. This qualitative study examined the ways
      one new destination public health agency responded to this demographic shift. The
      agency leveraged a culture of collaboration and a team approach so that serving
      immigrants became the responsibility of all workers, not only a few bilingual
      staff. Implications for practice including the potential benefits and pitfalls of
      including monolingual workers in immigrant clients' care are discussed.

PMID- 30095368
TI  - Laser Hair Depilation in the Treatment of Pilonidal Disease: A Systematic Review.
AB  - BACKGROUND: Laser hair depilation has shown promise in small series of patients
      with pilonidal sinus disease. The purpose of this study was to review the
      published literature on laser hair depilation in pilonidal disease to determine
      its effect on disease recurrence. METHODS: The PubMed, Embase, and Cochrane
      Central Register of Controlled Trials databases were searched to identify all
      studies published through December 1, 2017 that examined the role of laser hair
      depilation in the treatment of pilonidal sinus disease. Study characteristics,
      including design, treatment regimen, number of patients evaluated, rate of
      recurrence, and duration of follow up were recorded. RESULTS: Thirty-five
      published studies were included. Of these, 28 studies were retrospective and
      seven were prospective. There were five comparative studies: two retrospective,
      one prospective observational, and two randomized controlled trials. The number
      of patients included in each study ranged from one to 86 patients and patients
      received between one and 11 laser treatments. The pilonidal disease recurrence
      rate after laser depilation ranged from 0% to 28% at a mean follow-up ranging
      from 6 months to 5 years across studies. Four of the five studies that included a
      comparative group demonstrated a decreased recurrence rate compared to the non
      laser cohort. CONCLUSION: Laser hair depilation is a promising therapy in the
      management of pilonidal disease. However, the literature published to date is
      heterogeneous and has limited generalizability. Additional research is needed to
      determine the effectiveness of laser hair depilation to prevent pilonidal disease
      recurrence.

PMID- 30095370
TI  - Cultural differences in conceptual representation of "Privacy": A comparison
      between Iran and the United States.
AB  - Culture consists of shared conceptual representations in an individual's
      cognition. Thus, there may be cultural differences in the representation of a
      concept. To assess this possibility, we compared the subjective semantic
      structure of "privacy" in Iran and the United States. Participants were 200
      adults, 100 from Iran and 100 from the United States. In the first phase of the
      experiment, using the associative terms task, we detected nine of the most
      frequent terms that were associated with the concept of "privacy" in each
      culture. In the second phase, using the judged-similarity task, we asked
      participants to rate the degree to which each of the nine terms from the previous
      phase was associated with every other term and with the concept of "privacy."
      Results from a correspondence analysis model suggest similarities in the mapping
      of terms related to "privacy" along the dichotomous dimension of physical vs.
      informational concerns. However, cultural differences emerged in a second
      dimension, the extent to which individualism vs. collectivism was stressed. While
      "personal privacy" and an individual's relationship with the government was
      important for American adults, the main focus for Iranian adults was "familial
      privacy" and family-centered living.

PMID- 30095371
TI  - Y-Balance Test Performance and Leg Muscle Activations of Children with
      Developmental Coordination Disorder.
AB  - This study compared Lower Quarter Y-Balance Test (YBT-LQ) performance and leg
      muscle kinetics between children with and without developmental coordination
      disorder (DCD), and investigated the association between YBT-LQ performance and
      muscle kinetics in children with DCD. Forty-eight children with DCD and 51
      children without DCD participated in the study. Leg muscle kinetics were measured
      using surface electromyography when performing YBT-LQ. Children with DCD
      exhibited an overall lower YBT-LQ scores than controls. They had a lower peak
      gastrocnemius medialis activation for YBT-LQ posteromedial direction and shorter
      duration for the muscle to reach peak torque for YBT-LQ anterior direction. No
      relationship was found between YBT-LQ performance and leg muscle activations in
      children with DCD. Children with DCD exhibited a less competent YBT-LQ
      performance with atypical neuromuscular control.

PMID- 30095372
TI  - Source of Health Information and Unmet Healthcare Needs in Asian Americans.
AB  - BACKGROUND: Responding to the disparities in accessing and obtaining health
      information and healthcare among immigrant populations, the present study focused
      on Asian Americans. Using a sample that reflects Asian Americans' cultural and
      linguistic diversities, the goal was to explore the typologies of health
      information source and their predictability to unmet healthcare needs (i.e., the
      experience of not being able to get needed medical care). METHODS: Data were
      drawn from the 2015 Asian American Quality of Life Survey (N = 2,592), conducted
      using culturally and linguistically sensitive approaches. Latent class analysis
      on nine sources of health information across interpersonal networks (family
      members, close friends, acquaintances, and health professionals) and Internet
      based communication technologies (mobile apps, email listservs, social networking
      sites, online communities, and health websites) identified six classes: 'resource
      heavy,' 'human-oriented,' 'expertise-focused,' 'family-dominant,' 'resource
      scarce,' and 'health professional-dominant.' RESULTS: Compared to the resource
      heavy group, the odds of having an unmet healthcare need were 2.94 times greater
      in the family-dominant group and 4.13 times greater in the resource-scarce group.
      DISCUSSION: Findings provide implications for interventions with respect to
      subgroups to be prioritized and areas to be targeted in efforts to promote access
      and acquisition of health information and health services in Asian Americans.

PMID- 30095373
TI  - Auditing and Improving Surgical Antibiotic Prophylaxis.
AB  - BACKGROUND: There is extensive evidence of the efficacy of anti-microbial drugs
      in preventing infections from surgical efforts. Our objective was to describe the
      results obtained in our annual surgical antibiotic prophylaxis (SAP) audit in the
      years 2013-2017. METHODS: This was a retrospective observational study of SAP in
      surgical procedures carried out between 2013 and 2017 in a tertiary-level
      hospital. We examined the results from the services of general surgery, vascular
      surgery, neurosurgery, the breast unit, otolaryngology, maxillofacial surgery,
      traumatology, urology, pediatric surgery, gynecology, and plastic surgery.
      RESULTS: Establishment of six process quality indicators and their evaluation in
      the annual audit were carried out by the pharmacy service for approximately 500
      operations. The indicators that had a high percentage of compliance were
      indication for SAP, choice of anti-microbial agent, dose and route of
      administration, and administration of an intra-operative dose when this was
      appropriate. In contrast, time of administration of the first dose and duration
      of prophylaxis had a worse percentage of compliance. CONCLUSIONS: Compliance with
      the SAP protocols in our hospital is high. We consider that these better results
      are attributable to the establishment of quality indicators of SAP and to the
      annual audit that evaluates said indicators. Communication of the results
      obtained in the audit to the surgical services, which have as part of their
      objectives included in their management contracts compliance with said SAP
      protocols, encourages improvement. The use of prophylaxis kits is an improvement
      strategy that facilitates the correct choice of anti-microbial agent and prevents
      SAP from being prolonged inappropriately.

PMID- 30095374
TI  - Neural Mechanisms of Motion Processing in the Mammalian Retina.
AB  - Visual motion on the retina activates a cohort of retinal ganglion cells (RGCs).
      This population activity encodes multiple streams of information extracted by
      parallel retinal circuits. Motion processing in the retina is best studied in the
      direction-selective circuit. The main focus of this review is the neural basis of
      direction selectivity, which has been investigated in unprecedented detail using
      state-of-the-art functional, connectomic, and modeling methods. Mechanisms
      underlying the encoding of other motion features by broader RGC populations are
      also discussed. Recent discoveries at both single-cell and population levels
      highlight the dynamic and stimulus-dependent engagement of multiple mechanisms
      that collectively implement robust motion detection under diverse visual
      conditions.

PMID- 30095375
TI  - Health Needs and Experiences of a LGBT Population in Georgia and South Carolina.
AB  - The 2016 Municipal Equality Index rated Augusta, the largest city in the Central
      Savannah River Area (CSRA), as one of the least lesbian, gay, bisexual, and
      transgender (LGBT) friendly cities in America. To understand the context of our
      region in relation to LGBT wellness, we conducted the first LGBT health needs
      assessment of the CSRA, assessing physical and mental health status and health
      care needs and experiences in the community. Participants (N = 436) were
      recruited using venue and snowball sampling and completed an anonymous online
      survey. Overall, the health problems experienced (i.e., obesity, depression) were
      not uniformly experienced across sexual orientation and gender identity; some
      groups experienced significantly higher rates of these conditions than others.
      Similarly, transgender individuals in particular reported higher rates of
      negative experiences with health care providers. Regional and national
      dissemination of these findings is critical to reducing health disparities and
      improving wellness of our local LGBT community.

PMID- 30095377
TI  - Risk factors associated with musculoskeletal disorders among gemstone polishers
      in Jaipur, India.
AB  - PURPOSE: Gemstone polishing is a highly repetitive and strenuous job which may
      lead to musculoskeletal disorders (MSDs) among workers. This study aimed to
      determine the prevalence of MSDs and their contributing factors among gemstone
      polishers in Jaipur, India. MATERIALS AND METHODS: A self-reported questionnaire
      study was conducted among 388 male gemstone polishers. Current working postures
      of the participants were evaluated using rapid upper limb assessment. Results
      were considered significant at p <= 0.05. RESULTS: MSDs were highly prevalent
      among gemstone polishers, primarily in the lower back, neck, wrists/forearms and
      shoulders. Work-related factors including prolonged daily working hours, little
      recovery time, sustaining a non-neutral working posture, repetitive movements of
      upper limbs and individual factors including age and job tenure were
      significantly associated with MSDs in different body regions. Higher education
      led to a reduction in the occurrence of MSDs. Evaluation of working posture
      recommended further investigations and immediate changes in working habits of
      gemstone polishers to avoid serious harm and physical damage. CONCLUSION:
      Gemstone polishers in Jaipur are at high risk of developing MSDs in different
      body regions. Sustaining a non-neutral working posture for a long duration is a
      major risk factor in the current work setting.

PMID- 30095376
TI  - Disparate effects of antibiotics on hypertension.
AB  - Gut microbiota are associated with a variety of complex polygenic diseases. The
      usage of broad-spectrum antibiotics by patients affected by such diseases is an
      important environmental factor to consider, because antibiotics, which are widely
      prescribed to curb pathological bacterial infections, also indiscriminately
      eliminate gut commensal microbiota. However, the extent to which antibiotics
      reshape gut microbiota and per se contribute to these complex diseases is
      understudied. Because genetics play an important role in predisposing individuals
      to these modern diseases, we hypothesize that the extent to which antibiotics
      influence complex diseases depends on the host genome and metagenome. The current
      study tests this hypothesis in the context of hypertension, which is a serious
      risk factor for cardiovascular diseases. A 3 * 2 factorial design was used to
      test the blood pressure (BP) and microbiotal effects of three different
      antibiotics, neomycin, minocycline, and vancomycin, on two well-known,
      preclinical, genetic models of hypertension, the Dahl salt-sensitive (S) rat and
      the spontaneously hypertensive rat (SHR), both of which develop hypertension, but
      for different genetic reasons. Regardless of the class, oral administration of
      antibiotics increased systolic blood pressure of the S rat, while minocycline and
      vancomycin, but not neomycin, lowered systolic blood pressure in the SHR. These
      disparate BP effects were accompanied by significant alterations in gut
      microbiota. Our study highlights the need to consider an individualized approach
      for the usage of antibiotics among hypertensives, as their BP could be affected
      differentially based on their individual genetic and microbiotal communities.

PMID- 30095378
TI  - What Mindfulness can learn about Dissociation and what Dissociation can learn
      from Mindfulness.
AB  - Mindfulness based psychotherapeutic interventions have shown to be an effective
      intervention for quite some time now. These intervention, however, have not been
      that successful with individuals who experience dissociative disorders. There is
      a very clear disconnect between these two fields. In an attempt to close the gap,
      reviewing what mindfulness might be from an attachment and human developed lens,
      one can learn that there is a lot more occurring in a mindful state other than
      relaxation. There is a level of human development achievement that comes from a
      regular mindfulness practice that seems to play a role in raising our young and
      being part of a complex social group. Evidence suggests that the end product of
      mindfulness is likely deeply connected human relationships and balanced care
      giving abilities. In knowing the benefits from a relational perspective of
      mindfulness those in the dissociative world can utilize adaptations of
      mindfulness so that their clients can eventually learn to developed mindfulness
      and, in turn, have the same deeply connected relationship that they often missed.
      Conversely those in the mindfulness based therapeutic world can learn a lot about
      dissociation and harmed people by understanding the real difficulties that
      individuals with dissociative disorders have in experiencing a mindful state.
      They can learn to understand the need to adapt mindfulness based practices to
      accommodate individuals who have a system that is phobic of awareness, terrified
      of being calm and who have no concept of what non-judgement means. Both fields
      would benefit greatly by knowing more about the other.

PMID- 30095379
TI  - When Sexual Trauma Survivors with Severe Psychiatric Disabilities Experience
      Institutional Care.
AB  - Individuals with severe psychiatric disabilities face many challenges from their
      experience of mental health problems, but also from disenfranchisement,
      marginalization, and stigmatization from a sociocultural experience. Those who
      are sexual trauma survivors also have unique challenges and intersecting
      experiences, which are not historically well understood, acknowledged, or treated
      in U.S. systems of care. Both in historic and modern mental health systems there
      have been methods thought of as interventions that have been or are currently
      reported as traumatizing to those who experience them. This article highlights
      the specific challenges, needs, and organizational shifts that U.S. systems of
      care need to be aware of and embark upon in order to provide treatment that is
      more efficacious with and cognizant of the experiences of those who are sexual
      trauma survivors. Furthermore, new paradigms for providing mental health
      treatment are offered in the context of providing trauma-informed as well as
      trauma treatment to those who are sexual trauma survivors and experience severe
      psychiatric disabilities.

PMID- 30095380
TI  - Negotiating Theory When Doing Practice: A Systematic Review of Qualitative
      Research on Interventions to Reduce Homophobia.
AB  - We performed a systematic review of qualitative research on interventions to
      reduce homophobia. Specifically, we conducted a thematic analysis of participant
      feedback given in 30 qualitative and mixed-methods studies. Participants often
      described interventions as "eye-opening." However, they also criticized many
      interventions for their mismatch with the social, historical, or institutional
      context in which they were conducted. Some participants rejected the
      interventions altogether, describing them as offensive or disgusting. We drew
      three conclusions. First, participants not only were actively making sense of the
      interventions but also were often aware of philosophical and political tensions
      (especially liberal vs. queer approaches). Second, participants sometimes used
      the perceived inadequacy of the intervention for the local context as an argument
      to resist change. Finally, tensions in participant feedback (eye-opening vs.
      disgusting) can be read as evidence that reducing homophobia is "dirty work":
      such work is both vital for society and despised by many.

PMID- 30095381
TI  - A double-blind randomized controlled trial of the local application of vancomycin
      versus ampicillin powder into the operative field for thoracic and/or lumbar
      fusions.
AB  - OBJECTIVE Retrospective studies have reported that the local application of
      vancomycin (VCM) powder into the operative field decreases the incidence of
      surgical site infection (SSI) in thoracic and/or lumbar fusion. Authors of the
      present study prospectively evaluated the effects of VCM in patients undergoing
      thoracic and/or lumbar fusion. METHODS In this randomized double-blind trial, 230
      patients undergoing thoracic and/or lumbar fusion were randomly assigned to the
      local administration of VCM (interventional group, 1 g) or ampicillin (AMP;
      control group, 1 g) into the surgical field. The primary outcome was SSI results
      within 1 year of surgery. RESULTS The trial was prematurely stopped according to
      predetermined rules. The results showed one superficial infection (0.9%,
      Staphylococcus aureus) and one deep infection (0.9%, S. aureus) in the VCM group
      and two superficial infections (1.8%, Staphylococcus epidermidis and culture
      negative) and one deep infection (0.9%, methicillin-resistant S. aureus) in the
      AMP group. No significant differences in infection rates were observed between
      the groups (p = 0.8). CONCLUSIONS This double-blind randomized controlled trial
      demonstrated that the local application of VCM or AMP powder into the operative
      field in short thoracic and/or lumbar fusion procedures resulted in a similar
      incidence of SSI. ? CLASSIFICATION OF EVIDENCE Type of question: therapeutic;
      study design: randomized controlled trial; evidence: class III. Clinical trial
      registration no.: UMIN000009377 (umin.ac.jp/ctr).

PMID- 30095382
TI  - Lumbar tap-induced subarachnoid hemorrhage in a case of spinal epidural
      arteriovenous fistula.
AB  - The authors report the case of a 70-year-old woman with lumbar spinal epidural
      arteriovenous fistula (SEDAVF) who experienced subarachnoid hemorrhage (SAH)
      after a diagnostic lumbar puncture. According to the literature, perimedullary
      spinal vein enlargement is a hallmark of spinal vascular diseases; however, there
      are certain cases in which routine sagittal MRI fails to disclose signal flow
      voids. In such cases, patients may undergo a lumbar tap to investigate the
      possible causes of spinal inflammatory or demyelinating disease. Recognizing this
      phenomenon is essential because lumbar puncture of the epidural venous pouch or
      an enlarged intradural vein in SEDAVF may induce severe SAH. A high clinical
      index of suspicion can prevent similar cases in lumbar SEDAVF.

PMID- 30095383
TI  - The impact of age on surgical goals for spinopelvic alignment in minimally
      invasive surgery for adult spinal deformity.
AB  - OBJECTIVE Achieving appropriate spinopelvic alignment in deformity surgery has
      been correlated with improvement in pain and disability. Minimally invasive
      surgery (MIS) techniques have been used to treat adult spinal deformity (ASD);
      however, there is concern for inadequate sagittal plane correction. Because age
      can influence the degree of sagittal correction required, the purpose of this
      study was to analyze whether obtaining optimal spinopelvic alignment is required
      in the elderly to obtain clinical improvement. METHODS A multicenter database of
      ASD patients was queried. Inclusion criteria were age >= 18 years; an MIS
      component as part of the index procedure; at least one of the following: pelvic
      tilt (PT) > 20 degrees , sagittal vertical axis (SVA) > 50 mm, pelvic incidence
      to lumbar lordosis (PI-LL) mismatch > 10 degrees , or coronal curve > 20 degrees
      ; and minimum follow-up of 2 years. Patients were stratified into younger (< 65
      years) and older (>= 65 years) cohorts. Within each cohort, patients were
      categorized into aligned (AL) or mal-aligned (MAL) subgroups based on
      postoperative radiographic measurements. Mal-alignment was defined as a PI-LL >
      10 degrees  or SVA > 50 mm. Pre- and postoperative radiographic and clinical
      outcomes were compared. RESULTS Of the 185 patients, 107 were in the younger
      cohort and 78 in the older cohort. Based on postoperative radiographs, 36 (33.6%)
      of the younger patients were in the AL subgroup and 71 (66.4%) were in the MAL
      subgroup. The older patients were divided into 2 subgroups based on alignment;
      there were 26 (33.3%) patients in the AL and 52 (66.7%) in the MAL subgroups.
      Overall, patients within both younger and older cohorts significantly improved
      with regard to postoperative visual analog scale (VAS) scores for back and leg
      pain and Oswestry Disability Index (ODI) scores. In the younger cohort, there
      were no significant differences in postoperative VAS back and leg pain scores
      between the AL and MAL subgroups. However, the postoperative ODI score of 37.9 in
      the MAL subgroup was significantly worse than the ODI score of 28.5 in the AL
      subgroup (p = 0.019). In the older cohort, there were no significant differences
      in postoperative VAS back and leg pain score or ODI between the AL and MAL
      subgroups. CONCLUSIONS MIS techniques did not achieve optimal spinopelvic
      alignment in most cases. However, age appears to impact the degree of sagittal
      correction required. In older patients, optimal spinopelvic alignment thresholds
      did not need to be achieved to obtain similar symptomatic improvement.
      Conversely, in younger patients stricter adherence to optimal spinopelvic
      alignment thresholds may be needed.
      https://thejns.org/doi/abs/10.3171/2018.4.SPINE171153.

PMID- 30095384
TI  - Intraoperative real-time identification of abnormal vessels within the bright
      field by superselective arterial injection of saline and its slow-motion
      recording using a high frame rate digital camera during surgical treatment of
      spinal arteriovenous shunts: technical note.
AB  - The usefulness of superselective arterial injection of indocyanine green (SAI
      ICG) during the surgical treatment of a spinal arteriovenous shunts (AVSs) has
      occasionally been reported. However, SAI-ICG lacks the temporal resolution for
      recording rapid blood flow. The authors found that SAI of saline (SAIS) via a
      microcatheter renders the vessels transparent because of the replacement of
      intravascular blood with saline. By combining SAIS with SAI-ICG, they were able
      to identify abnormal vessels in the bright field during the surgical treatment of
      spinal AVS. Furthermore, they performed slow-motion video recording of blood flow
      in abnormal vessels by mounting a high frame rate (HFR) digital camera on the
      microscope eyepiece during SAIS. In this paper, the authors present two cases of
      patients with spinal AVSs. The first patient had a cervical dural arteriovenous
      fistula, and the second had a thoracic spinal arteriovenous malformation. SAIS
      delineated abnormal vessels within the bright field in real time in both cases.
      HFR video was recorded in the second case during SAIS. The slow-motion video
      showed a smooth and seamless motion of the blood flow in the feeding artery,
      which facilitated an understanding of the blood flow direction.

PMID- 30095385
TI  - Editorial.

PMID- 30095386
TI  - Biological sex and glucoregulation modulate postprandial cognition following
      dairy milk and fruit juice in healthy school-age children.
AB  - OBJECTIVES: Recent work suggests potential postprandial benefits for cognition
      and on-task behavior in children, depending on the macronutrients consumed, as
      well as individual differences such as sex and glucoregulation. We examined the
      effects of 1% milk versus apple juice on cognition and on-task behavior among
      healthy school-age children, predicting that milk would promote better
      performance and a greater presence of on-task behavior compared to juice. We also
      examined how sex and glucoregulation influenced cognition and behavior following
      each beverage. METHODS: Eighty-four English-speaking children ages 8-12 (45
      female, 39 male) attended two 0800 testing sessions after fasting overnight in a
      crossover design. Participant sessions were counterbalanced to include 237 mL of
      1% milk or apple juice. Behavioral measures and complex attentional and executive
      function tasks were assessed at baseline, 30, 90, and 120 min post-ingestion.
      Outcomes were analyzed using repeated measures mixed models. RESULTS:
      Participants with fasting glucose levels above 89.91 mg/dL responded more quickly
      in an inhibitory control paradigm following milk. Females performed faster on a
      vigilance task, but less accurately in a working memory paradigm after milk
      versus juice. No effects were found for on-task behavior. DISCUSSION: Results
      demonstrated modulatory effects of glucoregulation and sex on postprandial
      cognition. Milk may improve cognitive performance in school-aged children with
      higher fasting glucose, and may be the optimal choice for speed among females,
      whereas juice may be better for accuracy. Future work should utilize designs
      incorporating glucoregulation and sex, and consider additional biological
      variables to better understand postprandial cognition and behavior in children.

PMID- 30095389
TI  - International Committee on Systematics of Prokaryotes Subcommittee on the
      Taxonomy of Leptospiraceae. Minutes of the closed meeting, 28 November 2017,
      Palmerston North, New Zealand.

PMID- 30095390
TI  - Children are not small adults.

PMID- 30095387
TI  - Flavobacterium chryseum sp. nov. and Flavobacterium psychroterrae sp. nov., novel
      environmental bacteria isolated from Antarctica.
AB  - A group of rod-shaped, aerobic, Gram-stain-negative, gliding bacteria producing
      flexirubin-type pigment was isolated from environmental samples collected in
      Antarctica in 2009-2014. Phylogenetic analysis of the almost complete 16S rRNA
      gene sequences revealed two separated branches belonging to the genus
      Flavobacterium. Group I (n=8), represented by strain CCM 8826T, shared the
      highest sequence similarity to Flavobacterium collinsii 983-08T (98.8 %) and
      Flavobacterium saccharophilum DSM 1811T (98.4 %), and group II (n=4) represented
      by strain CCM 8827T shared the highest similarity to Flavobacterium aquidurense
      WB 1.1-56T (99.6 %). High genetic homogeneity of both groups, separation from
      each other and from phylogenetically close Flavobacterium species was verified by
      the rep-PCR fingerprinting method. DNA-DNA hybridization confirmed low genomic
      relatedness between strain CCM 8826T and F. collinsii 983-08T and F.
      saccharophilum DSM 1811T (18 and 28 %, respectively) and between strain CCM 8827T
      and F. aquidurense WB 1.1-56T (27 %). Chemotaxonomic analyses of strains CCM
      8826T and CCM 8827T revealed the respiratory quinone to be MK-6, the major
      identified polar lipid was phosphatidylethanolamine and the predominant polyamine
      was sym-homospermidine. The common major fatty acids were C15 : 0 iso, C17 : 0
      iso 3OH, C15 : 1 iso G, Summed Feature 3 (C16 : 1omega7c/C16 : 1omega6c), C15 : 0
      iso 3OH and additionally, C15 : 0 anteiso among group II members. All analyses
      confirmed that strains of group I and II represent two novel species of the genus
      Flavobacterium, for which the names Flavobacterium chryseum sp. nov. (type strain
      CCM 8826T=P3160T=LMG 30615T) and Flavobacterium psychroterrae sp. nov. (type
      strain CCM 8827T=P3922T=LMG 30616T) are proposed.

PMID- 30095388
TI  - Marinobacter fuscus sp. nov., a marine bacterium of Gammaproteobacteria isolated
      from surface seawater.
AB  - A Gram-stain-negative bacterium, designated NH169-3T, was isolated from a surface
      seawater sample of the South China Sea and subjected to a taxonomic polyphasic
      investigation. Strain NH169-3T was strictly aerobic, non-motile, non-spore
      forming and rod-shaped. The colony was 1.0-2.0 mm in diameter after the growth on
      marine agar at 30  degrees C for 72 h. The centre of the colony was smooth,
      circular, convex and brown with a transparent periphery. Strain NH169-3T was able
      to grow at temperatures between 4-40  degrees C (optimum, 37  degrees C), pH 5.5
      9.0 (pH 7.5) and with 0-12.5 % (w/v) NaCl (3.0 %). Chemotaxonomic analysis showed
      that the sole respiratory quinone of strain NH169-3T was ubiquinone 9; major
      fatty acids were C16 : 0 and C18 : 1omega9c, and major polar lipids were
      diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and one
      unidentified glycolipid. The DNA G+C content was 52.7 mol%. The comparison of 16S
      rRNA gene sequences showed that strain NH169-3T was closely related to
      Marinobacter shengliensis SL013A34A2T with a similarity of 98.0 %. Three
      phylogenetic trees reconstructed with neighbour-joining, maximum-parsimony and
      maximum-likelihood methods using 16S rRNA gene sequences showed that strain NH169
      3T was grouped into a separated branch with M. shengliensis SL013A34A2T in a
      clade of the genus Marinobacter and closely related to Marinobacter halophilus
      JCM 30472T, Marinobacter vinifirmus DSM 17747T and Marinobacter
      hydrocarbonoclasticus DSM 8798T. Analyses of both phenotypic and phylogenetic
      properties have suggested that strain NH169-3T was distinctive from species with
      validly published names in genus Marinobacter. Thus, strain NH169-3T (=MCCC
      1K03455T=KCTC 62226T) is proposed as a novel species in genus Marinobacter with
      the name Marinobacter fuscus sp. nov.

PMID- 30095391
TI  - Immunotherapy for house-dust mite allergy.
AB  - BACKGROUND: Since the discovery of house-dust mites (HDM) in the 1960's, allergy
      immunotherapy trials that used extracts of these mites have been conducted, first
      by subcutaneous (SCIT) and later by the sublingual (SLIT) route. When reviewed in
      2013, published studies of HDM immunotherapy were found to often be characterized
      by small sample size, widely varying doses, and poorly defined disease severity
      and outcomes. These trials were thought to to support the efficacy of HDM
      subcutaneous allergy immunotherapy but the evidence for efficacy of sublingual
      immunotherapy was less firm. METHODS: This report will review a large number of
      well-designed studies reported since 2013, mostly of SLIT, and in particular, of
      two newly developed HDM sublingual tablets. In addition, other aspects of HDM
      immunotherapy will be addressed, including use in atopic dermatitis, optimum
      duration of treatment, evidence for disease modification and use with adjuvants.
      RESULTS: Seventeen reports on 15 randomized, double-blind, placebo-controlled
      trials were identified as having been published since the cut-off date of the
      2013 systematic review. Twelve of these reported results with the 2 HDM SLIT
      tablets. These studies clearly established the appropriate doses and the efficacy
      and safety of these tablets in treating allergic rhinitis and asthma. Other
      reports offered support for use of HDM immunotherapy in selected patients with
      atopic dermatitis, for administration of HDM immunotherapy for 3 to 5 years, for
      anticipating disease modification after 3-5 years of treatment, and for the use
      of vitamin D and selected probiotics to enhance its efficacy. CONCLUSION: HDM
      SCIT and SLIT-tablet therapy have demonstrated effectiveness in allergic rhinitis
      and asthma. Appropriate dosing with HDM SLIT-liquid has not been established
      although a limited number of studies suggest it can be effective as well. HDM
      SCIT and HDM SLIT share efficacy in allergic rhinitis and asthma, disease
      modification and the duration of treatment required to produce persisting
      benefit.

PMID- 30095392
TI  - Early life obesity increases the risk for asthma in San Francisco born Latina
      girls.
AB  - BACKGROUND: Previous studies showed that youths who are obese are more likely to
      have asthma; however, some studies found important sex differences in the risk
      for asthma. METHODS: We retrospectively assessed the asthma incidence in a Latino
      cohort of children recruited from birth and followed up until 9 years of age. We
      subsequently assessed risk factors for asthma and for an early asthma (defined as
      <4 years of age) diagnosis in relation to obesity. Asthma was assessed via
      maternal reports and medical records review of the children at 9 years of age.
      Each child's weight and height were collected annually. Independent and sex
      specific risk factors for asthma diagnosis were assessed by using multivariable
      logistic regression models. RESULTS: In our cohort, 24.6% (42/164) of the
      children were diagnosed with asthma by 9 years of age. The mean +/- standard
      deviation age of asthma diagnosis was 29.5 +/- 4.5 months; 79.5% had a diagnosis
      of asthma at <4 years of age. In girls, any breast-feeding at 6 months was
      associated with a reduced risk of asthma (odds ratio [OR] 0.21 [95% confidence
      interval {CI}, 0.05-0.86]) and obesity at 2 years of was associated with
      increased risk for asthma (OR 12.14 [95% CI 2.79-53.05]). Exposure to
      environmental toxins and consumption of sugar-sweetened beverages were associated
      with a risk for asthma diagnosis after 4 years of age. CONCLUSION: In our high
      risk Latino cohort, obesity was associated with asthma development in the girls.
      In addition, an asthma diagnosis after 4 years of age may be related to
      environmental toxin exposure and early consumption of sugar-sweetened beverages
      compared with an earlier diagnosis.

PMID- 30095394
TI  - Efficacy and safety of omalizumab in pediatric patients with high immunoglobulin
      E levels: A case series.
AB  - BACKGROUND: The efficacy and safety of omalizumab has been demonstrated in
      children as young as 6 years of age. Omalizumab is currently approved for a range
      of immunoglobulin E (IgE) levels that differ by age. In patients with IgE levels
      higher than the indicated therapeutic window, only a few studies have
      demonstrated the efficacy and safety of its use. Specifically, no reported
      studies exist to describe the use of omalizumab in pediatric patients with asthma
      ages <12 years and with high IgE levels. OBJECTIVE: We reported a series of
      pediatric patients who were initiated on omalizumab despite an IgE level higher
      than the age-indicated therapeutic windows and aimed to describe whether
      omalizumab was safe and improved asthma outcomes. METHODS: Patients who initiated
      omalizumab in our pediatric allergy clinic between January 2008 and December
      2015, with serum IgE levels higher than the age-indicated therapeutic ranges were
      included. Patient charts were reviewed to determine the number of asthma-related
      events in the 12 months before and after initiation of omalizumab and the Asthma
      Control TestTM scores at the time of initiation and at 12 months of therapy.
      RESULTS: Eleven patients were identified with pretreatment IgE levels higher than
      the age-approved thresholds. Five patients were ages <12 years, and six patients
      were ages >12 years. For all but one patient, the maximum recommended dose of 375
      mg every 2 weeks was effective in reducing the need for corticosteroids,
      emergency department visits, or hospitalizations in the year after initiation of
      therapy. During the period of therapy, there were no reports of severe reactions.
      CONCLUSION: Despite a small study group, our results indicated that omalizumab
      may be safely used in pediatric patients with IgE levels higher than the
      indicated therapeutic windows.

PMID- 30095393
TI  - Allergic sensitization and clinical outcomes in urban children with asthma, 2013
      2016.
AB  - BACKGROUND: The aim of this study was to examine if food and/or aeroallergen
      sensitization was associated with worse asthma, pulmonary function tests (PFT),
      and laboratory markers. METHODS: At our institution, 386 children with asthma
      were divided into allergic and nonallergic groups based on allergen-specific
      immunoglobulin E (IgE) testing classes 1-6 versus 0. Asthma severity and/or
      control, IgE level, eosinophil counts and/or percentages, forced vital capacity
      (FVC), forced expiratory volume in the first second of expiration (FEV1), and
      FEV1/FVC, were compared by using bivariate, regression, and subgroup analyses for
      children who were highly allergic (>=4 allergens). RESULTS: A total of 291
      subjects with asthma were allergic, significantly older, and had higher mean IgE
      levels and eosinophil counts and percentages (all p < 0.001). A total of 203
      subjects who were highly allergic had worse obstruction on PFTs. Increasing age
      predicted allergen sensitization after confounder adjustment, odds ratio (OR)
      1.54 (95% confidence interval [CI], 1.18-2.02). Similarly, PFT obstruction was
      associated with multiple allergen sensitization (OR 0.97 [95% CI, 0.93-1.02]).
      CONCLUSION: Increasing age predicted allergic sensitization and multiple allergen
      sensitization. Worse obstruction on PFT also predicted multiple allergen
      sensitization. Continued surveillance of aeroallergen sensitization and PFT
      results may be beneficial in asthma management, particularly in older urban
      children.

PMID- 30095395
TI  - Predictors of asthma relapse in patients who attended an emergency department.
AB  - BACKGROUND: Patients with asthma exacerbations and frequent relapses that require
      admission to the emergency department (ED) often have more severe disease, worse
      quality of life, and higher use of health care resources. OBJECTIVE: The aim of
      this study was to identify potential predictors of relapse after patients are
      treated in an ED for an asthma exacerbation. METHODS: A retrospective,
      noninterventional cohort study was conducted in adult patients who attended the
      ED of a tertiary hospital in 2014 for an asthma exacerbation. We analyzed the
      subpopulation who experienced at least one relapse (returned to the ED < 15 days
      after the previous event). RESULTS: Fifty-two of 831 patients experienced 66
      relapses after going to the ED (mean +/- standard deviation [SD] age, 58.5 +/-
      23.4 years). The average +/- SD probability of a relapse was 6 +/- 0.8%. The
      frequency of episodes was higher in May and November. Twenty-four patients had
      >=260 blood eosinophils/MUL, including 17 who had >=400 eosinophils/MUL. Only 15%
      of the patients were referred to an asthma specialist at discharge. Factors
      related to a higher probability of relapse were the following: having multiple
      visits to the ED in 1 year, uncontrolled asthma, wheezing in the pulmonary
      auscultation, peripheral eosinophilia with >=400 eosinophils/ MUL, and being
      discharged in the first visit to the ED (p < 0.01 for all). CONCLUSION: In this
      population, patients who had multiple ED visits in 1 year, those with
      uncontrolled asthma, wheezing, >=400 blood eosinophils/MUL, or who had been
      discharged at the first ED visit are at higher risk of relapse.

PMID- 30095396
TI  - Penicillin skin testing in the management of penicillin allergy in an outpatient
      pediatric population.
AB  - BACKGROUND: Eight to ten percent of patients believe that they are allergic to
      penicillin, yet only 10% of those patients have evidence of an immunoglobulin E
      (IgE) mediated allergy upon penicillin skin testing (PST). In the adult
      population, a negative PST result is associated with a low risk of immediate
      reaction on oral challenge, but further studies are needed in the pediatric
      population. OBJECTIVE: To calculate the negative predictive value (NPV) of the
      current skin testing regimen of penicillin, benzylpenicilloyl-polylysine (the
      major determinant), and ampicillin in a pediatric outpatient population to assess
      the utility of adding the minor determinant mixture to the skin testing regimen.
      METHODS: A retrospective chart review was conducted of all pediatric patients
      seen in a single-center pediatric allergy/immunology outpatient clinic between
      January 1, 2010, and March 1, 2016, who underwent PST for presumed penicillin
      drug allergy. RESULTS: Only 38% of patients who underwent PST had a drug reaction
      history consistent with an IgE-mediated reaction. 28.8% of the patients had a
      positive PST result. The addition of ampicillin to the standard PST regimen of
      penicillin and benzylpenicilloyl-polylysine identified an additional 4.1% of
      patients. Two patients (3.2%) reacted on oral challenge with a minor rash. The
      NPV of the PST regimen was 98%. No significant predictive variables for a
      positive PST result were identified. CONCLUSION: Given the high NPV of the
      current PST regimen, we do not recommend additional testing with the minor
      determinant mixture. Despite this high NPV, the utility of PST in the low-risk,
      low-pretest probability outpatient pediatric population was limited, and select
      patients may be able to proceed directly to oral challenge.

PMID- 30095398
TI  - A 69-year-old woman with periodic fever, facial swelling, and neck pain.
AB  - We presented a case of a 69-year-old woman who experienced monthly episodes of
      facial swelling and nonpruritic, erythematous rash on her face, accompanied by
      high fever, nausea, headache, and neck pain over 1 year. Her symptoms started
      with myalgia, arthralgia, fever and neck stiffness, and headache, and then
      angioedema occurred, which was painful to touch. She underwent multiple
      iatrogenic diagnostic and therapeutic procedures that did not lead to the correct
      diagnosis. Subsequently, relevant immunology laboratory tests were conducted
      after a careful history and physical examination, which led to the diagnosis.
      This case illustrated the need for a detailed history and thorough immunologic
      assessment, and the requirement to maintain a broad differential diagnosis.

PMID- 30095397
TI  - Pitfalls in anaphylaxis diagnosis and management at a university emergency
      department.
AB  - BACKGROUND: Some previous reports revealed suboptimal management of anaphylaxis
      (ANX) in the emergency department (ED). OBJECTIVE: To evaluate the recorded
      diagnosis and management of patients who presented with ANX at our university
      hospital ED and to assess how the management correlated with the severity of the
      case and the training level of the ED staff. METHODS: A descriptive study that
      involved reviewing the electronic medical records of patients who presented with
      ANX at the ED during a period of 4 years. RESULTS: When reviewing 1341 charts of
      potential cases, 60 met the criteria for ANX, but only 23% were correctly coded.
      Inaccurate coding was noted in 77%, mainly as an "allergic reaction." Systemic
      corticosteroids were administered in the ED to 85% of the patients and H1
      antihistamines to 73%; only 20% received epinephrine. Ten patients required
      hospital admission, and, on discharge, only four patients (40%) were given
      epinephrine autoinjector prescriptions. Of the 50 who were discharged home, 48%
      were given epinephrine autoinjector prescriptions and 16% were given a referral
      for allergy evaluation. CONCLUSION: The observed low rates of appropriate
      diagnostic coding of ANX, of epinephrine administration, epinephrine autoinjector
      prescribing at discharge, and referral for allergy evaluation call for more
      education on these issues. Some of these pitfalls can be partly attributed to the
      setting in a university ED where health providers are usually busy in rendering
      urgent care.

PMID- 30095399
TI  - For the Patient.

PMID- 30095400
TI  - Differences in cytokine levels between the nasal polyps of adolescents with local
      allergic and adolescents with allergic or nonallergic rhinitis.
AB  - BACKGROUND: Local allergic rhinitis (LAR) is rhinitis with a localized nasal
      allergic response in the absence of systemic allergy. This study aimed to
      evaluate the pathogenesis specific to LAR compared with allergic rhinitis (AR)
      and nonallergic rhinitis (NAR) by using cytokines from polypous tissues. METHODS:
      We recruited 43 patients with AR (n = 15; mean age, 17.4 years), LAR (n = 12;
      mean age, 15.9 years), and NAR (n = 16; mean age, 15.6 years) who underwent
      polypectomy. Atopic status was defined as presenting a sufficiently high total
      immunoglobulin E (IgE) serum concentration and skin-prick test or serum allergen
      test. Immunoassays were performed by using polyp tissue homogenates to quantify
      the levels of regulated on activation of normal T cell expressed and secreted
      (RANTES), tumor necrosis factor (TNF) alpha, interleukin (IL) 5, and sera to
      assess total IgE and eosinophil cationic protein. RESULTS: RANTES levels were
      higher in patients with LAR than in patients with AR and NAR. There was a
      significant correlation in the concentration of RANTES between polyp tissue
      homogenates and serum (R2 = 0.51, p < 0.05). The levels of IL-5, TNF alpha, and
      interferon gamma also demonstrated positive correlations between polyp tissue
      homogenates and serum; however, they were not significantly different.
      CONCLUSION: Results of our study indicated that RANTES may play an important role
      and contribute to allergic reaction in LAR, and RANTES may be related to the
      pathogenesis of LAR.

PMID- 30095401
TI  - Feasibility of structured light plethysmography for the evaluation of lung
      function in preschool children with asthma.
AB  - BACKGROUND: Structured light plethysmography (SLP) is a new noninvasive
      technology to capture the movement of the thoracic and abdominal wall, and to
      assess some parameters indicative for lung function. OBJECTIVE: The purpose of
      the study was to evaluate the feasibility of SLP in children with asthma.
      METHODS: A total of 52 patients were enrolled: 25 with asthma exacerbation (group
      1), 13 with well-controlled asthma (group 2), and 14 healthy controls (group 3).
      Every patient underwent SLP evaluation and a lung function test. RESULTS: SLP
      evaluations showed that the ratio of inspiratory flow at 50% of tidal volume (Vt)
      to expiratory flow at 50% of Vt, in which Vt is taken to be the exhaled chest
      wall movement, and flow is taken to be the time derivative of the chest wall
      movement (IE50) value increased in group 1 compared with groups 2 and 3, with
      statistical significance (p = 0.018); the data were consistent with the
      spirometry parameter. A correlation between the IE50 and forced expiratory volume
      in the first second of expiration was highlighted (r = -0.35, p = 0.019).
      CONCLUSION: SLP assessed airway obstruction, and its use in clinical practice
      could be applied in preschool children in future studies.

PMID- 30095402
TI  - Erratum.

PMID- 30095403
TI  - Adverse Health Outcomes Among Industrial and Occupational Sectors in Michigan.
AB  - INTRODUCTION: We used data from the Michigan Behavioral Risk Factor Surveillance
      System (MIBRFSS) to estimate the prevalence of adverse health outcomes by
      industry and occupation and to examine the association of adverse health outcomes
      with industry and occupation while controlling for demographics and personal
      lifestyle behaviors. METHODS: We calculated the prevalence of adverse health
      outcomes by industry by using data from the 2013-2015 MIBRFSS. Adjusted
      prevalence of adverse health outcomes was calculated by industry and occupation
      by using logistic regression for survey design, adjusting for demographics and
      health behaviors, and was compared with the overall prevalence in all industries
      and occupations. RESULTS: Three industries had a significantly higher prevalence
      of current asthma, diabetes, and depression compared with prevalence among
      workers employed in all industries. After controlling for confounding factors,
      only Health Care and Social Assistance had significantly higher prevalence of a
      health outcome, depression (20.1%). Three occupations had significantly higher
      prevalence of chronic obstructive pulmonary disease, current asthma, depression,
      high blood pressure, and diabetes compared with workers employed in all
      occupations. After adjusting for all confounding factors, only one occupation,
      protective service, had a significantly higher prevalence of high blood pressure
      (37.3%) and diabetes (12.8%). CONCLUSION: Adverse health outcomes varied
      significantly by industry and occupation in Michigan. Employers, policy makers,
      and health promotion practitioners can use results based on BRFSS to target and
      prioritize worksite wellness programs. MIBRFSS data also suggested the need for
      further research to identify why some industries had higher risks for diabetes,
      hypertension, and depression after controlling for covariates.

PMID- 30095404
TI  - Changes in Physical Activity After Installation of a Fitness Zone in a Community
      Park.
AB  - INTRODUCTION: Increases in physical activity can lead to decreases in the
      prevalence of chronic diseases. Parks provide an ideal setting for physical
      activity. We investigated the effect of a fitness equipment installation on the
      intensity of park users' physical activity at a community park. METHODS: We used
      the System for Observing Play and Recreation in a Community to record physical
      activity in Eastgate Park in Garden Grove, California, in August 2015
      (preintervention [n = 1,650 person-periods]) and in February 2016
      (postintervention [n = 1,776 person-periods]). We quantified physical activity in
      target areas of the park during 15-minute observation periods in 2 ways: 1) we
      categorized each user's activity level during the period (sedentary, walking,
      vigorous), and 2) we converted activity levels to numeric metabolic equivalent
      task (MET) scores and calculated the period-average score across users. We used
      mixed-effects regression models to assess 1) the proportional odds of higher
      activity level at postintervention and 2) the association between intervention
      status (pre vs post) and mean period-average MET scores. RESULTS: In the
      immediate zone around the fitness equipment, the odds ratio for a higher activity
      level was 1.58 (95% confidence interval [CI], 1.14-2.18; P = .006) and the mean
      period-average MET score was 0.33 (95% CI, -0.07 to 0.74; P = .11) units higher
      at postintervention. Across the park as a whole, the odds ratio for a higher
      activity level was 1.41 (95% CI, 1.21-1.63; P < .001), and the mean period
      average MET score was 0.34 (95% CI, 0.12-0.56; P = .003) units higher at
      postintervention. CONCLUSION: Installing fitness zones appears to be an effective
      intervention for increasing physical activity of park users. Further studies need
      to be conducted to understand the sustained impact of fitness zones over time.

PMID- 30095405
TI  - Increasing Colorectal Cancer Screening in Health Care Systems Using Evidence
      Based Interventions.

PMID- 30095407
TI  - Reaching the limit.
AB  - How many copies of a protein can be made before it becomes toxic to the cell?

PMID- 30095406
TI  - Estimating the protein burden limit of yeast cells by measuring the expression
      limits of glycolytic proteins.
AB  - The ultimate overexpression of a protein could cause growth defects, which are
      known as the protein burden. However, the expression limit at which the protein
      burden effect is triggered is still unclear. To estimate this limit, we
      systematically measured the overexpression limits of glycolytic proteins in
      Saccharomyces cerevisiae. The limits of some glycolytic proteins were up to 15%
      of the total cellular protein. These limits were independent of the proteins'
      catalytic activities, a finding that was supported by an in silico analysis. Some
      proteins had low expression limits that were explained by their localization and
      metabolic perturbations. The codon usage should be highly optimized to trigger
      the protein-burden effect, even under strong transcriptional induction. The S-S
      bond-connected aggregation mediated by the cysteine residues of a protein might
      affect its expression limit. Theoretically, only non-harmful proteins could be
      expressed up to the protein-burden limit. Therefore, we established a framework
      to distinguish proteins that are harmful and non-harmful upon overexpression.

PMID- 30095411
TI  - Nanotechnological approaches for the development of herbal drugs in treatment of
      diabetes mellitus - a critical review.
AB  - Diabetes mellitus (DM) is a chronic illness that requires continuing medical care
      and patient self-management education to prevent acute complications and to
      reduce the risk of long-term complications. The number of people with diabetes is
      increasing due to population growth, ageing, urbanisation and increasing
      prevalence of obesity and physical inactivity. Apart from currently available
      therapeutic options, many herbal medicines have been recommended for the
      treatment of diabetes. Herbal drugs are prescribed widely because of their
      effectiveness, less side effects and relatively low cost. Several pharmacopoeias
      have provided parameters to maintain quality and standardise procedures in
      identification/authentication of herbal inputs and their products. Available
      literature related to folklore medicine used in the treatment of diabetes
      extended to nanoformulation of herbal drugs up to date was cited. The use of
      bioactive compounds leads to new hope to improve the life expectancy and health
      status of the population for the formulation of novel drugs. Recently, many
      studies have shown that nanotechnology has the potential to be used in different
      biological and medical applications, mainly as targeted drug delivery systems to
      minimise and delay the chronic effects of diabetes. Herein, the authors presented
      a thorough review of the available herbal medicines and the possibilities of
      developing their nanoformulations in the treatment of DM.

PMID- 30095410
TI  - Magnetic nanoparticles: a versatile carrier for enzymes in bio-processing
      sectors.
AB  - Many industrial processes experience the advantages of enzymes which evolved the
      demand for enzymatic technologies. The enzyme immobilisation technology using
      different carriers has trustworthy applications in industrial biotechnology as
      these techniques encompass varied advantages such as enhanced stability, activity
      along with reusability. Immobilisation onto nanomaterial is highly favourable as
      it includes almost all aspects of science. Among the various techniques of
      immobilisation, the uses of nanoparticles are remarkably well perceived as these
      possess high-specific surface area leading to high enzyme loadings. The magnetic
      nanoparticles (MNPs) are burgeoning in the field of immobilisation as it possess
      some of the unique properties such as high surface area to volume ratio, uniform
      particle size, biocompatibility and particularly the recovery of enzymes with the
      application of an external magnetic field. Immobilisation of industrially
      important enzymes onto nanoparticles offers overall combined benefits. In this
      review, the authors here focus on the current scenario in synthesis and
      functionalisation of MNPs which makes it more compatible for the enzyme
      immobilisation and its application in the biotechnological industries.

PMID- 30095412
TI  - Development of colorimetric cholesterol detection kit using TPU
      nanofibre/cellulose acetate membrane.
AB  - In this study, the authors report a simple fabrication of thermoplastic
      polyurethane (TPU) nanofibres-based kit for cholesterol detection. TPU is a
      polymer that is highly elastic, resistant to microorganisms, abrasion and
      compatible with blood; thus, making it a natural selection as an immobilisation
      matrix for cholesterol oxidase (ChOx) enzyme. The nanofibre was fabricated by
      electrospinning process and was characterised using scanning electron microscopy
      and Fourier transform-infrared spectroscopy. ChOx was covalently immobilised on
      TPU nanofibre and cholesterol level/concentration was visually found using 4
      aminoantipyrine, a dye that reacts with H2O2 produced from the oxidation of
      cholesterol by ChOx and changes colour from yellow to red. The efficacy of the
      nanofibre to act as a detecting substrate was compared with cellulose acetate
      (CA) membrane, a well-documented enzyme immobilisation matrix. The optimisation
      of enzyme concentration and dye quantity were performed using standard ChOx
      spectrophotometric assay and the same was used in CA membrane and TPU nanofibre.
      The ChOx immobilised nanofibre showed good linear range from 2 to 10 mM with a
      lower detection limit of 2 mM and was highly stable compared to that of CA
      membrane. The enzyme immobilised nanofibre was further validated in serum
      samples.

PMID- 30095408
TI  - E proteins sharpen neurogenesis by modulating proneural bHLH transcription
      factors' activity in an E-box-dependent manner.
AB  - Class II HLH proteins heterodimerize with class I HLH/E proteins to regulate
      transcription. Here, we show that E proteins sharpen neurogenesis by adjusting
      the neurogenic strength of the distinct proneural proteins. We find that
      inhibiting BMP signaling or its target ID2 in the chick embryo spinal cord,
      impairs the neuronal production from progenitors expressing ATOH1/ASCL1, but less
      severely that from progenitors expressing NEUROG1/2/PTF1a. We show this context
      dependent response to result from the differential modulation of proneural
      proteins' activity by E proteins. E proteins synergize with proneural proteins
      when acting on CAGSTG motifs, thereby facilitating the activity of ASCL1/ATOH1
      which preferentially bind to such motifs. Conversely, E proteins restrict the
      neurogenic strength of NEUROG1/2 by directly inhibiting their preferential
      binding to CADATG motifs. Since we find this mechanism to be conserved in
      corticogenesis, we propose this differential co-operation of E proteins with
      proneural proteins as a novel though general feature of their mechanism of
      action.

PMID- 30095413
TI  - Surface modification affect the biodistribution and toxicity characteristics of
      iron oxide magnetic nanoparticles in rats.
AB  - Various surface modifications of iron oxide magnetic nanoparticles (IOMNs) can
      improve their stability and long-term retention time in vivo, expanding
      applications of biomedical fields. However, whether the long-term retention of
      IOMNs coated with different surface modifications has toxic effects remains
      poorly understood. Here, the toxicity of IOMNs modified with polyethylene glycol
      (PEG), bovine serum albumin (BSA), and carboxyl group (COOH), forming PEG-IOMNs,
      BSA-IOMNs, and COOH-IOMNs, respectively, were evaluated in the rats. The high
      accumulation of PEG-IOMNs and COOH-IOMNs both in the liver and lung, and the high
      accumulation BSA-IOMNs in blood after 24 day recovery were observed by elemental
      content analysis. Except individual neutrophils in the local portal area, PEG
      IOMNs can also induce cytoplasmic vacuolisation in partial liver cells by
      histopathological examination. Furthermore, the results of RT-qPCR showed that
      PEG-IOMNs, BSA-IOMNs, and COOH-IOMNs can change the transcript levels of most
      genes related to iron homeostasis, mitochondria apoptosis, inflammatory response,
      but <2-fold alteration. COOH-IOMNs seemed to induce normal cell apoptosis more
      easily than BSA-IOMNs and PEG-IOMNs. In conclusion, BSA-IOMNs had longer-term
      retention time in blood. IOMNs coated with PEG and BSA can still induce side
      effects on the liver.

PMID- 30095414
TI  - Stimulation of secondary metabolites by copper and gold nanoparticles in submerge
      adventitious root cultures of Stevia rebaudiana (Bert.).
AB  - Nanotechnology is one of the advance technologies that almost found implications
      in every field of science. The importance is due to the unique properties of
      nanoparticles. In this study, bimetallic alloys of copper (Cu) and gold (Au) were
      tested in submerge root cultures of Stevia rebaudiana for production of biomass
      and secondary metabolites. A known amount of inoculum roots were submerged in
      liquid Murashige and Skoog medium containing combination of naphthalene acetic
      acid (NAA; 0.5 mg l-1) and different ratios of nanoparticles (NPs). NAA augmented
      medium was used as control. The addition of nanoparticles (30 ug l-1) stimulated
      biomass accumulation (1.447 g/flask) on 27th day of log phases. The maximum total
      phenolics content (TPC; 16.17 mg/g-DW) and total flavonoids content (TFC; 4.20
      mg/g-DW) were displayed using AuCu-NPs (1:3) and NAA. The same combinations
      enhanced total phenolic production (TPP; 116 mg/L) and total flavonoid production
      (TFP; 29.5 mg/L) in submerged cultures. A strong correlation was observed between
      phenolics, flavonoids and dry biomass. Moreover, maximum 1, 1-diphenyl-2
      picrylhydrazyl (DPPH) activity of 79% was displayed by addition of AuCu (1:3)
      nanoparticles. In conclusion, nanoparticles application has shown a positive
      effect in enhancing biomass and secondary metabolites production in adventitious
      root cultures of Stevia rebaudiana.

PMID- 30095409
TI  - Human axial progenitors generate trunk neural crest cells in vitro.
AB  - The neural crest (NC) is a multipotent embryonic cell population that generates
      distinct cell types in an axial position-dependent manner. The production of NC
      cells from human pluripotent stem cells (hPSCs) is a valuable approach to study
      human NC biology. However, the origin of human trunk NC remains undefined and
      current in vitro differentiation strategies induce only a modest yield of trunk
      NC cells. Here we show that hPSC-derived axial progenitors, the posteriorly
      located drivers of embryonic axis elongation, give rise to trunk NC cells and
      their derivatives. Moreover, we define the molecular signatures associated with
      the emergence of human NC cells of distinct axial identities in vitro.
      Collectively, our findings indicate that there are two routes toward a human post
      cranial NC state: the birth of cardiac and vagal NC is facilitated by retinoic
      acid-induced posteriorisation of an anterior precursor whereas trunk NC arises
      within a pool of posterior axial progenitors.

PMID- 30095415
TI  - Green synthesis of silver nanoparticles using Glaucium corniculatum (L.) Curtis
      extract and evaluation of its antibacterial activity.
AB  - The metal nanoparticles, due to interesting features such as electrical, optical,
      chemical and magnetic properties, have been investigated repeatedly. Also, the
      mentioned nanoparticles have specific uses in terms of their antibacterial
      activity. The biosynthesis method is more appropriate than the chemical method
      for producing the nanoparticles because it does not need any special facilities;
      it is also economically affordable. In the current study, the silver
      nanoparticles (AgNPs) were obtained by using a very simple and low-cost method
      via Glaucium corniculatum (L.) Curtis plant extract. The characteristics of the
      AgNPs were investigated using techniques including: X-ray diffraction,
      transmission electron microscopy (TEM), scanning electron microscopy (SEM), and
      Fourier transform infrared spectroscopy. The SEM and TEM images showed that the
      nanoparticles had a spherical shape, and the mean diameter of them was 53.7 and
      45 nm, respectively. The results of the disc diffusion test used for measuring
      the anti-bacterial activity of the synthesised nanoparticles indicated that the
      formed nanoparticles possessed a suitable anti-bacterial activity.

PMID- 30095416
TI  - Toxicological impact of TiO2 nanoparticles on Eudrilus euginiae.
AB  - The concern regarding the toxicological effects of nanoparticles (NPs) on the
      terrestrial environment is increasing. To avoid risks of exposure to these NPs in
      the environment, it is essential to develop an understanding of their reactivity,
      toxicity, and persistency. Due to the increased usage of nano-titanium dioxide
      (TiO2) in various industrial products, an exponential increase in exposure is
      expected, which would exacerbate concerns about its ecological risks. The present
      study is conducted to evaluate the size-dependent effects of TiO2 NPs on the
      soil, especially on earthworm (Eudrilus euginiae). To date, many studies have
      been reported on the impact of TiO2 NPs on ecotoxicology. However,
      histotoxicology studies are sparse. This study serves to be the first report on
      the size-dependent histotoxicological impact of nano-TiO2 on earthworms
      particularly, E. euginiae. This report presents an intensive overall view of the
      longer time ecotoxicological impact of TiO2 nanomaterials on various biological
      parameters of earthworms at cellular levels. The results show that the survival
      and growth of adult earthworms are severely affected by the TiO2 NPs in the soil,
      which substantiates the adverse effects of TiO2 NPs on earthworms.

PMID- 30095417
TI  - Biosynthesis of AgNPs by B. maydis and its antifungal effect against Exserohilum
      turcicum.
AB  - In the present study, Bipolaris maydis was used to synthesise silver
      nanoparticles (AgNPs). Several parameters that influence the synthesis of AgNPs
      such as fungus age, the concentration of Ag nitrate (AgNO3), and incubation time
      were explored to find the optimum synthesis condition. Furthermore, the
      antifungal activity of AgNPs against Exserohilum turcicum was determined by
      measuring inhibition zone diameter, colony formation, and conidia germination.
      The optimal biosynthesis system included fungus age of 7 days, 8 mM AgNO3, and an
      incubation time of 120 h. Under these conditions, synthesised NPs were near
      round, and the average particle size was about 21 nm. At the experiment, the
      diameter of the inhibition zone reached a maximum of 8 mM AgNO3 and 72 h. In
      addition, the inhibition rate of colony and conidia reached 83.39 and 100%,
      respectively, with 200 MUg/ml AgNPs. The results offer a novel pathway for
      phytopathogen control and make it likely to develop new eco-friendly
      antimicrobial.

PMID- 30095419
TI  - Apoptotic efficacy and antiproliferative potential of silver nanoparticles
      synthesised from aqueous extract of sumac (Rhus coriaria L.).
AB  - Currently, nanotechnology and nanoparticles (NPs) are recognised due to their
      extensive applications in medicine and the treatment of certain diseases,
      including cancer. Silver NPs (AgNPs) synthesised by environmentally friendly
      method exhibit a high medical potential. This study was conducted to determine
      the cytotoxic and apoptotic effects of AgNPs synthesised from sumac
      (Anacardiaceae family) fruit aqueous extract (AgSu/NPs) on human breast cancer
      cells (MCF-7). The anti-proliferative effect of AgSu/NPs was determined by MTT
      assay. The apoptotic properties of AgSu/NPs were assessed by morphological
      analysis and acridine orange/propidium iodide (AO/PI) and DAPI staining. The
      mechanism of apoptosis induction in treated cells was investigated using
      molecular analysis. Overall results of morphological examination and cytotoxic
      assay revealed that AgSu/NPs exert a concentration-dependent inhibitory effect on
      the viability of MCF-7 cells (IC50 of ~10 umol/48 h). AO/PI staining confirmed
      the occurrence of apoptosis in cells treated with AgSu/NPs. In addition,
      molecular analysis demonstrated that the apoptosis in MCF-7 cells exposed to
      AgSu/NPs was induced via up-regulation of Bax and down-regulation of Bcl-2. These
      findings suggested the potential use of AgSu/NP as cytotoxic and pro-apoptotic
      efficacy and its possible application in modern medicine for treating certain
      disorders, such as cancer.

PMID- 30095418
TI  - Nano-zero valent iron impregnated cashew nut shell: a solution to heavy metal
      contaminated water/wastewater.
AB  - The present research is focused on the removal of Zn(II) ions from aqueous
      solution using nano zero-valent iron impregnated cashew nut shell (NZVI-CNS). The
      present system was investigated in batch mode operation. NZVI-CNS was prepared by
      the liquid-phase reduction process. The results showed that the NZVI-CNS
      exhibited superior adsorption capacity for the removal of Zn(II) ions. Adsorption
      isotherm and kinetic models were applied to explain the nature of the adsorption
      process. Adsorption kinetic data followed the pseudo-first order kinetic model.
      Moreover, the equilibrium adsorption data were best fitted with a Freundlich
      model. Langmuir monolayer adsorption capacity was calculated as 94.46 mg of
      Zn(II) ions/g of NZVI-CNS. The thermodynamic parameters explain that the present
      adsorption system was measured as feasible and spontaneous. This newly prepared
      adsorbent can be successfully applied for the different industrial wastewater
      treatment. Finally, the exploration asks about contemplated that NZVI-CNS has
      exhibited unrivalled adsorption limit. Additionally, NZVI-CNS is believed to be
      extremely green and monetarily neighbourly help for wastewater treatment. The
      results indicate that the feasible approach could be applied in agricultural
      waste biomass materials for the productive expulsion of heavy metals from aqueous
      solution and reusing agricultural wastes to facilitate their disposal problem.

PMID- 30095420
TI  - Synthesis, characterisation and bactericidal effect of ZnO nanoparticles via
      chemical and bio-assisted (Silybum marianum in vitro plantlets and callus
      extract) methods: a comparative study.
AB  - Currently, the evolution of green chemistry in the synthesis of nanoparticles
      (NPs) with the usage of plants has captivated a great response. In this study, in
      vitro plantlets and callus of Silybum marianum were exploited as a stabilising
      agent for the synthesis of zinc oxide (ZnO) NPs using zinc acetate and sodium
      hydroxide as a substitute for chemical method. The contemporary investigation
      defines the synthesis of ZnO NPs prepared by chemical and bio-extract-assisted
      methods. Characterisation techniques such as X-ray diffraction, scanning electron
      microscopy, Fourier transform infrared spectroscopy and energy dispersive X-ray
      were used to confirm the synthesis. Although chemical and bio-assisted methods
      are suitable choices for NPs synthesis, the bio-assisted green assembly is
      advantageous due to superior stability. Moreover, this report describes the
      antibacterial activity of the synthesised NPs against standard strains of
      Klebsiella pneumonia and Bacillus subtilis.

PMID- 30095421
TI  - Aggregation of silver nanoplates in the presence of L-cysteine and the
      application for separation.
AB  - A facile method was investigated to fabricate the aggregated silver nanoplates as
      products for separation materials. Initially, ageing of L-cysteine capped silver
      nanoplates in ethanol solvent led to fast aggregation. Then, the as-formed
      aggregates were easily prepared as powder due to the highly volatile properties
      of ethanol. Interestingly, the aggregated powder would be soluble again after the
      dispersion in water and the re-dispersed nanoplates could be obtained.
      Furthermore, the heavy metal ions such as Cu2+, Pb2+ and Hg2+ would soon
      accelerate the aggregation of the dispersed silver nanoplates again. The
      reversible aggregation process could be employed for separation applications in
      the future.

PMID- 30095422
TI  - Simplistic approach in extracellular synthesis of silver nanoparticles via
      bioreducing potential of Planococcus plakortidis strain BGCC-51 isolated from dye
      industry effluent soil.
AB  - Here, extracellular synthesis of silver nanoparticles (AgNPs) was carried out by
      Planococcus plakortidis strain BGCC-51 isolated from dye industry effluent soil.
      The microbes were isolated, screened, and characterised by molecular analysis
      (accession number KX776160). The optimisation of synthesis of AgNPs to determine
      the optimum substrate level (1-5 mM), pH (5-9), and temperature (25-55 degrees C)
      were further carried out. P. plakortidis strain BGCC-51 gave best yield of AgNPs
      at substrate concentration 5 mM, pH 8, and at 35 degrees C. Synthesised AgNPs
      were characterised by scanning electron microscope and high-resolution
      transmission electron microscope. The size of synthesised AgNPs was in the range
      of 20-40 nm having spherical morphology. The AgNPs were found to show
      antimicrobial activity against bacteria such as Escherichia coli (ATCC 25922),
      Pseudomonas aeruginosa (ATCC 27853), and Staphylococcus aureus (ATCC 29213).

PMID- 30095423
TI  - Poly (E-caprolactone)-chitosan-poly (vinyl alcohol) nanofibrous scaffolds for
      skin excisional and burn wounds in a canine model.
AB  - Poly (E-caprolactone)-chitosan-poly (vinyl alcohol) (PCL: Cs: PVA) nanofibrous
      blend scaffolds were known as useful materials for skin wound healing and would
      help the healing process about 50% faster at the final time point. From the
      previous studies by the authors, PCL: Cs: PVA (in 2: 1: 1.5 mass ratio)
      nanofibres showed high efficacy in healing on rat models. In this study, the
      scaffolds were examined in burn and excision wounds healing on dogs as bigger
      models. The scaffolds were applied on dorsum skin wounds (n = 5) then macroscopic
      and microscopic investigations were carried out to measure the wounds areas and
      to track healing rate, respectively. Macroscopic results showed good aspect
      healing effect of scaffolds compared with control wounds especially after 21 days
      post-operating for both cutting and burn wounds. Pathological studies showed that
      the healing rates of the wounds covered with PCL: Cs: PVA nanofibrous scaffolds
      were much rapid compared to untreated wounds in control group. The immunogenicity
      of the scaffolds in canine model was also investigated. The findings showed that
      nanofibrous blend scaffolds was not immunogenic in humoural immune responses. All
      these results indicated that PCL: Cs: PVA nanofibrous web could be considered as
      promising materials for wounds healings.

PMID- 30095424
TI  - Biofabrication of silver nanoparticles using bacteria from mangrove swamp.
AB  - The last decade has observed a rapid advancement in utilising biological system
      towards bioremediation of metal ions in the form of respective metal
      nanostructures or microstructures. The process may also be adopted for respective
      metal nanoparticle biofabrication. Among different biological methods, bacteria
      mediated method is gaining great attention for nanoparticle fabrication due to
      their eco-friendly and cost-effective process. In the present study, silver
      nanoparticle (AgNP) was synthesised via continuous biofabrication using Aeromonas
      veronii, isolated from swamp wetland of Sunderban, West Bengal, India. The
      biofabricated AgNP was further purified to remove non-conjugated biomolecules
      using size exclusion chromatography, and the purified AgNPs were characterised
      using UV-visible spectroscopy, X-ray diffraction, field emission scanning
      electron microscopy and transmission electron microscopy (TEM). Additionally, the
      presence of proteins as capping and stabilising agents was confirmed by the amide
      I and amide-II peaks in the spectra obtained using attenuated total reflection
      Fourier transform infrared spectroscopy. The size of biofabricated AgNP was 10-20
      nm, as observed using TEM. Additionally, biofabricated AgNP shows significant
      antibacterial potential against E. coli and S. aureus. Hence, biofabricated AgNP
      using Aeromonas veronii, which found resistant to a significant concentration of
      Ag ion, showed enhanced antimicrobial activity compared to commercially available
      AgNP.

PMID- 30095425
TI  - Magnetic soy protein isolate-bovine serum albumin nanoparticles preparation as a
      carrier for inulinase immobilisation.
AB  - Magnetic nanoparticles (NPs) were functionalised with soy protein isolate (SPI)
      and bovine serum albumin (BSA) for inulinase immobilisation. The results revealed
      the nanomagnetite size of about 50 nm with a polydispersity index (PDI) of 0.242.
      The average size of the SPI NPs prepared by using acetone was 80-90 nm (PDI,
      0.277), and SPI-BSA NPs was 80-90 nm (PDI, 0.233), and their zeta potential was
      around -34 mV. The mean diameter of fabricated Fe3O4@SPI-BSA NPs was <120 nm
      (PDI, 0.187). Inulinase was covalently immobilised successfully through
      glutaraldehyde on Fe3O4@SPI-BSA NPs with 80% enzyme loading. Fourier transform
      infrared spectra, field emission scanning electron microscopy, and transmission
      electron microscopy images provided sufficient proof for enzyme immobilisation on
      the NPs. The immobilised inulinase showed maximal activity at 45 degrees C, which
      was 5 degrees C higher than the optimum temperature of the free enzyme. Also, the
      optimum pH of the immobilised enzyme was shifted from 6 to 5.5. Thermal stability
      of the enzyme was considerably increased to about 43% at 75 degrees C, and Km
      value was reduced to 25.4% after immobilisation. The half-life of the enzyme
      increased about 5.13-fold at 75 degrees C as compared with the free form.
      Immobilised inulinase retained over 80% of its activity after ten cycles.

PMID- 30095426
TI  - In vitro antibacterial activity of ceftazidime, unlike ciprofloxacin, improves in
      the presence of ZnO nanofluids under acidic conditions.
AB  - The development of antibiotic resistance among hospital pathogens has provided a
      great need for new antimicrobial agents. Zinc oxide nanoparticles (ZnO NPs) in
      combination with various antibiotics can act as a reducing agent for antibiotic
      resistance. The aim of this study was to investigate the influence and the
      mechanism of ZnO NPs on the antimicrobial activity of ciprofloxacin (CP) and
      ceftazidime (CAZ) against Enterococcus faecalis (E. faecalis) and Acinetobacter
      baumannii (A. baumannii) bacteria in acidic conditions (pH 5.5). ZnO NPs were
      synthesised using the solvothermal method and characterised. The MIC90 value of
      ZnO NPs against A. baumannii was 0.25 mg ml-1 and its highest growth-inhibitory
      activity was observed at 0.125 mg ml-1 for E. faecalis. The Fourier transform
      infrared spectroscopy spectra of ZnO NPs treated with antibiotics showed the
      interaction between ZnO NPs and each of the two antibiotics. ZnO NPs at a sub
      inhibitory concentration had no effect on the antibacterial activity of CP and
      CAZ against E. faecalis and CP against A. baumannii. The action mechanism of ZnO
      NPs for enhancing the antibacterial efficacy of CAZ against A. baumannii was
      evaluated. ZnO NPs caused to increase in the antibacterial activity of CAZ
      against A. baumannii, possibly through the release of Zn2+ and increasing of
      membrane permeability.

PMID- 30095427
TI  - Formulation of garlic oil-in-water nanoemulsion: antimicrobial and
      physicochemical aspects.
AB  - Despite the unique properties, application of garlic essential oil (GEO) is too
      limited in food and drugs, due to its low water solubility, very high volatility
      and unpleasant odour. In this work, a nanoemulsion containing GEO was formulated
      to cover and protect the volatile compounds of GEO. The encapsulation efficiency
      of formulated nanoemulsions was measured by gas chromatography and obtained
      encapsulation efficiency ranged from 91 to 77% for nanoemulsions containing 5-25%
      GEO, respectively. The 2,2-diphenyl-1-picrylhydrazyl method for antioxidant
      activity measurement showed that free radical scavenging capacity of
      nanoemulsions intensified during storage time. The electrical conductivity of the
      samples was constant over storage time while linearly increased by raising the
      temperature. Thermogravimetric analysis was used to determine the thermal
      resistance of nanoemulsions and their ingredients. Interestingly, microbial tests
      cleared that the control nanoemulsion with a particle size below 100 nm
      (nanoemulsion without GEO) also showed antimicrobial activity. Disk diffusion
      method showed that pure GEO and also formulated nanoemulsions had a stronger
      effect against Gram-positive bacterium (Staphylococcus aureus) than Gram-negative
      bacterium (Escherichia coli).

PMID- 30095429
TI  - Tree gum stabilised selenium nanoparticles: characterisation and antioxidant
      activity.
AB  - Selenium nanoparticles (Se NPs) were synthesised using sodium borohydride as a
      reductant and gum kondagogu as a stabiliser. Plant gum serves as a renewable, non
      toxic, non-immunogenic, biopolymer based feedstock. Role of gum on synthesis and
      mean particle size was studied using ultraviolet-visible spectroscopy and dynamic
      light scattering. NP generation was visualised with orange red colouration and
      NPs exhibited a surface plasmon resonance peak at 250 nm. Formed NPs were
      amorphous, polydisperse and spherical. NPs showed a bimodal distribution, size
      varied from 44.4 to 200 nm and mean particle size was 105.6 nm. NP solution
      exhibited a zeta potential of -39.9 mV, confirming the superior stability. In
      comparison to ionic Se, the gum capped Se NPs exhibited superior 1, 1-diphenyl-2
      picrylhydrazyle and 2, 2-azinobis-(3-ethylbenzthinzoline-6-sulphonic acid) radial
      scavenging activities of 73.2 and 92.2%, respectively, at 25 ug/ml. Antibacterial
      potential of NPs was checked with well diffusion assay. NPs exhibited growth
      inhibition activity against Gram-positive bacteria only. Bacillus subtilis and
      Micrococcus luteus showed respective inhibition zones of 6.3 and 8.6 mm at 12 ug.
      Thus, the present study demonstrates the applicability of tree gum stabilised Se
      NPs as a potent antioxidant nutrition supplement at a much lower dose, in
      comparison with ionic Se.

PMID- 30095428
TI  - Cytotoxicity of biologically synthesised bismuth nanoparticles against HT-29 cell
      line.
AB  - This study was purposed to examine the cytotoxicity and functions of biologically
      synthesised bismuth nanoparticles (Bi NPs) produced by Delftia sp. SFG on human
      colon adenocarcinoma cell line of HT-29. The structural properties of Bi NPs were
      investigated using transmission electron microscopy, energy dispersive X-ray, and
      X-ray diffraction techniques. The cytotoxic effects of Bi NPs were analysed using
      flow cytometry cell apoptosis while western blot analyses were applied to analyse
      the cleaved caspase-3 expression. Oxidative stress (OS) damage was determined
      using the measurement of the glutathione (GSH) and malondialdehyde (MDA) levels
      and antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) levels.
      The half maximal inhibitory concentration (IC50) value of Bi NPs was measured to
      be 28.7 +/- 1.4 ug/ml on HT-29 cell line. The viability of HT-29 represented a
      concentration-dependent pattern (5-80 ug/ml). The mode of Bi NPs induced
      apoptosis was found to be mainly related to late apoptosis or necrosis at IC50
      concentration, without the effect on caspase-3 activities. Furthermore, Bi NPs
      reduced the GSH and increased the MDA levels and decreased the SOD and CAT
      activities. Taken together, biogenic Bi NPs induced cytotoxicity on HT-29 cell
      line through the activation of late apoptosis independent of caspase pathway and
      may enhance the OS biomarkers.

PMID- 30095430
TI  - Effects of surface sterilisation with green synthesised silver nanoparticles on
      Lamiaceae seeds.
AB  - Nanoparticles have been used in many areas of biotechnology. In this study, an
      alternative surface sterilisation method was established for plant tissue
      cultures. Silver nanoparticles synthesised via green synthesis were used for the
      surface sterilisation of Lamiaceae seeds (Salvia farinecae, Ocimum basilicum -
      Large Leaf Italian, Thymus vulgaris, Ocimum basilicum var. purpurascens). Water
      extracts of dried Alkanna tinctorum rhizomes and Syzygium aromaticum flowers were
      utilised in the bioreduction of silver ions. The seeds were exposed to 0, 1, 7,
      14 and 28 day-old colloidal solutions of silver nanoparticles and their effects
      on germination and surface sterilisation were determined. Fresh (0 and 1 day-old)
      colloidal solutions of silver nanoparticles were found very effective on surface
      sterilisation (100%). Moreover, they showed no negative effect on both
      germination and morphology of plantlets. It was shown that silver nanoparticles
      can be used as a surface sterilisation agent and they have no adverse effects on
      seed germination and in vitro plantlet growth.

PMID- 30095432
TI  - Green synthesis of silver nanoparticles and their applications as colorimetric
      probe for determination of Fe3+ and Hg2+ ions.
AB  - Silver nanoparticles (AgNPs) were prepared by a green method using Cordia myxa
      leaf extract. They were characterised by UV-vis spectroscopy, Fourier transform
      infrared spectroscopy and their X-ray diffraction pattern. Their sizes were
      determined by scanning electron micrographs, transmission electron micrographs
      imaging and dynamic light scattering analysis. The shapes of nanoparticles were
      spherical or truncated triangular and their average size was determined to be
      51.6 nm. Their solution was stable at least for one month. The prepared AgNPs
      were used as a selective chemical sensor for determination of iron(III) (only
      when Cl- ions were present in the medium) and mercury(II) ions with detection
      limits of 0.084 and 0.037 nM, respectively. It was shown that the mechanism of
      these detections is through oxidation of Ag atoms by Fe3+ and Hg2+ ions.

PMID- 30095431
TI  - Evaluating the effect of green synthesised copper oxide nanoparticles on
      oxidative stress and mitochondrial function using murine model.
AB  - Green synthesis of metal nanoparticles (NPs) has now received the attention of
      researchers due to ease of preparation and its potential to overcome hazards of
      these chemicals for an eco-friendly milieu. In this study, copper oxide (CuO) NPs
      were synthesised via Desmodium gangeticum aqueous root extract and standard
      chemical method, further characterised by UV-visible spectroscopy, Fourier
      transform infrared spectroscopy, X-ray diffraction, Thermogravimetric analysis
      and scanning electron microscopy. The nephrotoxicity of the NP obtained from two
      routes were compared and evaluated at subcellular level in Wistar rat, renal
      proximal epithelial cells (LLC PK1 cell lines) and isolated renal mitochondria.
      CuO NP synthesised by chemical route showed prominent nephrotoxicity measured via
      adverse cytotoxicity to LLC PK1 cells, elevated renal oxidative stress and damage
      to renal tissue (determined by impaired alanine transaminase, aspartate
      transaminase, urea, uric acid and creatinine in the blood). However, at the level
      of cell organelle, CuO NP from both routes are non-toxic to mitochondrial
      functional activity. The authors' finding suggests that CuO NP synthesised by
      chemical route may induce nephrotoxicity, but may be overcome by co
      administration of antioxidants, as it is not mito-toxic.

PMID- 30095433
TI  - Green synthesis of titanium dioxide nanoparticles with volatile oil of Eugenia
      caryophyllata for enhanced antimicrobial activities.
AB  - Different chemo-physical methods are used to synthesise titanium oxide
      nanoparticles (TiO2 NPs), which are often expensive, unfriendly to the
      environment, toxic, not biocompatible, with a small yield. To resolve these
      problems, the researchers use green procedures to synthesise TiO2-NPs by plant
      extracts of Capsicum annum L. and Allium cepa (onion) and characterise using
      atomic force microscopy, scanning electron microscopy, transmission electronic
      microscopy, X-ray diffraction, ultraviolet (UV)-visible (Vis) spectra and Fourier
      transform infrared spectroscopy. The results indicate that most NPs synthesised
      by the first and second procedures of onion had an average diameter of 95.7 and
      89.1 nm, while NPs synthesised by C. annum had an average diameter of 103.60 and
      90.07 nm, respectively. In UV-Vis spectra, strong absorption was below 470 nm,
      and energy gap was 3.3 eV in each of the first procedure of A. cepa and the
      second procedure of C. annum compared with 270 nm, 6.3 eV for each of the second
      procedure of A. cepa and the first procedure of C. annum. The antimicrobial
      activities of NPs were evaluated and an attempt was made to enhance these
      activities by Eugenia caryophyllata plant's oil in combination therapies. There
      were synergistic effects between NPs and plant's oil.

PMID- 30095434
TI  - Seed germination and biochemical profile of Citrus reticulata (Kinnow) exposed to
      green synthesised silver nanoparticles.
AB  - The biosynthesis of silver nanoparticles (AgNPs) is substantial for its
      applications in different fields. The Moringa oleifera leaves were used as
      reducing and stabilising agent for the biosynthesis of AgNPs. The synthesised
      AgNPs were characterised through UV-visible spectroscopy, zeta analyser, scanning
      electron microscopy (SEM) and energy dispersive Xray (EDX). In this study,
      effects of the synthesised AgNPs were also evaluated on nucellus tissues
      germination frequency and biochemical parameters of plant tissues. Nucellus
      tissues of Citrus reticulata were inoculated on MS medium supplemented with 10,
      20, 30 and 40 ug/ml suspension of the synthesised AgNPs. Green synthesised AgNPs
      enhanced the in vitro germination because of low toxicity and nonfriendly issues.
      Significant results were obtained for germination parameters i.e. root and shoot
      length and seedling vigour index in response to 30 ug/ml suspension of green
      synthesised AgNPs. The 30 u/ml suspension of AgNPs also enhanced antioxidant
      activity (41%) and SOD activity (0.36 nM/min/mg FW) while total phenolic content
      (4.7 ug/mg FW) and total flavonoid content (1.1 ug/mg FW) was significantly high
      when MS medium was fortified with 40 ug/ml suspension of the synthesised AgNPs.
      The content of total protein was significant (558 ug/BSA Eq/mg FW) in control
      plantlets as compared to the other treatments.

PMID- 30095435
TI  - Association of characteristics of HBV quasispecies with hepatitis B surface
      antigen seroconversion after pegylated interferon-alpha-2a treatment in child
      patients.
AB  - BACKGROUND: The correlation between hepatitis B surface antigen (HBsAg)
      seroconversion and the characteristics of HBV quasispecies (QS) before and during
      pegylated interferon-alpha-2a (PEG-IFN-alpha-2a) treatment in hepatitis B e
      antigen (HBeAg)-positive chronic hepatitis B (CHB) children has not yet been
      reported. METHODS: 35 patients, including 18 HBsAg seroconverters (SS) and 17 non
      seroconverters (SN), were enrolled. Serum samples were collected before treatment
      and at weeks 12 and 24 of treatment. Sequences within the basal core promoter/pre
      core (BCP/PC) and S/reverse transcriptase (S/RT) region were analysed by next
      generation sequencing. RESULTS: There was no significant difference in the
      baseline diversity of HBV QS (Shannon entropy [Sn]; Hamming distance [HD]) in
      either region between the two groups. The baseline mutations A1762T/G1764A,
      C1913A, and T2003A/G or C2004T were correlated with non-response to therapy
      (P=0.025, P=0.036, P=0.032, respectively). After 24 weeks of therapy, HBV
      diversity within the BCP/PC region in the SS group notably declined (Sn: P=0.002;
      HD: P=0.011), while that of the SN group was nearly unchanged. As for the S/RT
      region, 24 weeks of treatment made no significant difference on QS diversity in
      either group. CONCLUSIONS: Our data demonstrated that the baseline viral
      mutations and dynamic changes in HBV QS diversity within the BCP/PC region were
      closely related to HBsAg seroconversion in HBeAg-positive CHB children treated
      with PEG-IFN-alpha-2a.

PMID- 30095436
TI  - Interlayer excitons in transition-metal dichalcogenide heterostructures with type
      II band alignment.
AB  - Combining ab initio density functional theory with the Dirac-Bloch and gap
      equations, excitonic properties of transition-metal dichalcogenide hetero
      bilayers with type-II band alignment are computed. The existence of interlayer
      excitons is predicted, whose binding energies are as large as 350 meV, only
      roughly 100 meV less than those of the coexisting intralayer excitons. The
      oscillator strength of the interlayer excitons reaches a few percent of the
      intralayer exciton resonances and their radiative lifetime is two orders of
      magnitude larger than that of the intralayer excitons.

PMID- 30095437
TI  - In situ exploration of the thermodynamic evolution properties in the type II
      interface from the WSe2-WS2 lateral heterojunction.
AB  - The mutual interaction of the type II heterointerface can be very susceptible to
      the variation of electron states, introducing differences into the band structure
      and the band alignment in comparison to their pristine states. Here, the thermal
      evolution of the exciton transition and electronic properties inside the
      covalently bonded type II interface of the atomically planar WSe2-WS2 lateral
      heterojunction has been studied. With the aid of luminescence and electronic
      evolution, it was found that the coupling at the heterointerface is strong, and
      that the change in the photon-electron transition with temperature is weak.
      Meanwhile, by employing some quantitative computational methods, the temperature
      variation of the extracted built-in electric field at the interface is
      unexpectedly pronounced, resulting from the thermodynamical spanning behaviors of
      the electrons, as well as the strains generated by the difference in the thermal
      expansion coefficient between the structural lattice. In addition, the electric
      contact at the interface shows a negative temperature correlation. The present
      findings provide a vital contribution to the photo-electron interaction-based
      application and evaluation paths of the electric contact in two-dimensional
      transition metal dichalcogenide-based devices.

PMID- 30095438
TI  - Multi-walled carbon nanotubes under focused electron beam: metal passivation
      effect and nanoscaled curvature effect.
AB  - The elongation and length contraction in multi-walled carbon nanotubes
      without/with metal (Au) nanoparticles under focused electron beam irradiation is
      in situ studied experimentally at room temperature with transmission electron
      microscopy. It is observed that the plastic flow and direct evaporation of carbon
      atoms strongly rely on the nanoscaled negative curvature and surface energy of
      the nanotubes. The multi-walled carbon nanotubes without metal nanoparticles
      shrink and elongate by the diffusion and plastic flow of carbon atoms along the
      shells in the tube axis direction by self contraction of shells. In contrast,
      multi-walled carbon nanotubes with metal nanoparticles shrink and reduce their
      lengths by direct evaporation (sputtering) of carbon atoms into the free space
      under passivation by the metal nanoparticles. Thus, experimental demonstration is
      provided that the non-uniform structural evolution process in multi-walled carbon
      nanotubes induced fleetly by the nanoscaled negative curvature effect under
      athermal activation effect of electron beam passivates by metal nanoparticles.

PMID- 30095440
TI  - Investigation of cold atmospheric plasma treatment in polydimethylsiloxane
      microfluidic devices with a transmural method.
AB  - Here we report a transmural testing that proves cold atmospheric plasma (CAP) can
      be used to treat the aqueous samples in polydimethylsiloxane (PDMS) microfluidic
      devices. The reactive species of CAP are found to be able to pass through the
      PDMS wall and interact with the aqueous medium in the microchannels. The H2O2
      concentration, pH value and the bacterial survival number of the treated medium
      are detected, respectively, to evaluate the feasibility of this method. The
      relationship between the concentration of H2O2 in the aqueous samples and the
      thickness of the channel wall is explained by the diffusion mechanism of plasma
      species in PDMS. The acidification (i.e. decrease of pH value) and sterilization
      effect of plasma are also observed in the treated samples. This transmural method
      allows the CAP treatment in PDMS microfluidic devices, which demonstrates that
      the plasma biomedicine would have potential applications in biomicrofluidics.

PMID- 30095439
TI  - Switchable Rashba effect by dipole moment switching in an Ag2Te monolayer.
AB  - Because of the surface depolarization field, there is a critical thickness for
      ferroelectricity in ultrathin ferroelectric films, hindering miniaturization of
      high-density nonvolatile memory storage devices. A controllable Rashba effect by
      external electric field via switchable dipole moment could be a promising way to
      control and manipulate the spin degrees of freedom in spintronics. Here, based on
      first principles calculations, we show that non-planar Ag2Te monolayer, which has
      been recently predicted to be a topological insulator, possess a switchable out
      of-plane electric dipole moment. The switching of the dipole can be realized by
      the penetration of Te atoms through the hexagonal Ag-plane. Additionally, non
      planar Ag2Te shows a giant Rashba spin-splitting ([Formula: see text] eV A) due
      to the out-of-plane electric dipole moment. Our tight binding model indicates
      that the origin of such large [Formula: see text] is the large inversion symmetry
      breaking term ([Formula: see text] eV), which is one order of magnitude larger in
      non-planar Ag2Te monolayer compared with other Rashba materials. Interestingly,
      the Rashba effect can be turned on/off by the phase transition from non-planar to
      planar structure via Te displacement. Moreover, the spin-texture can be
      completely reversed because of switchable electric dipole moment. Our work shows
      a new way to realize ferroelectric-like dipole moment switching and consequently
      switchable Rashba spin-splitting, which may facilitate a nonvolatile electrical
      control of the spin degrees of freedom, down to the monolayer thickness,
      promising potential applications to electrically controlled spintronic devices.

PMID- 30095441
TI  - An Autopsy Case of Injuries Caused by Automobile Dragging for a Distance of 3.4
      km Without Thoracoabdominal Organ Injuries.
AB  - Dragging injuries caused by automobiles involved in an accident are occasionally
      reported; however, those without injury to the thoracoabdominal organs are rare.
      We present an autopsy case of a man in his 20s found dead on the road after being
      dragged by a passenger automobile for a distance of 3.4 km. The accident caused
      fatal dragging injuries but no thoracoabdominal injuries. The victim appeared to
      be drunk and was lying on the road in front of the parked automobile. Dragging
      injuries are a unique type of traffic accident that sometimes result from limited
      and poor visibility due to darkness, rain, or fog. In particular, lying on the
      road in a drunken state is a specific risk factor for dragging injuries. The
      dragging distance, road-surface properties, strength of pressure applied by the
      underbody of the automobile, and the victim's posture are considered to affect
      the distribution and degree of dragging injuries. Based on autopsy findings and
      eyewitness testimonies, we discuss the injury mechanism and attempt to
      reconstruct the accident.

PMID- 30095442
TI  - Police Interactions Among Neuropathologically Confirmed Dementia Patients:
      Prevalence and Cause.
AB  - OBJECTIVE: The aim of this study was to investigate and compare the prevalence
      and recurrence of police interaction (PI) with patients diagnosed with dementia.
      We also aimed to study the reason behind the PI, the time of occurrence of PI,
      and potential consequences of the PI. METHODS: For this retrospective medical
      records' review, we included 281 cases with a neuropathologic dementia diagnosis
      from the Department of Pathology, Region Skane/Lund University, between 1967 and
      2013. The diagnoses were Alzheimer disease, frontotemporal lobar degeneration,
      vascular dementia, and mixed dementia. A prerequisite was that extensive clinical
      investigation and follow-up had been conducted at the Department of Geriatric
      Psychiatry in Lund. RESULTS: Of the 281 patients studied, 50 (18%) had a history
      of interacting with the police during the course of their disease. Frontotemporal
      dementia patients had a relatively higher prevalence of PI and more often due to
      criminal behavior. The recurrence of PIs differed among the groups;
      frontotemporal dementia patients exhibited a higher PI recurrence compared with
      the other groups. CONCLUSIONS: The patterns of PIs differ between the
      frontotemporal dementia and Alzheimer disease patients. Knowledge about such
      differences may be of value for the police, the judiciary system, and the society
      in general.

PMID- 30095443
TI  - Osteoblastic bone response mimicking bone progression during treatment with
      pembrolizumab in advanced cutaneous melanoma.
AB  - Pembrolizumab is an immune checkpoint inhibitor approved for the treatment of
      patients with unresectable or metastatic melanoma. Appearance of bone metastases,
      either osteolytic or osteoblastic, during treatment qualifies as disease
      progression. We report the case of a 64-year-old White woman with a metastatic
      melanoma undergoing second-line treatment with pembrolizumab. At first
      evaluation, after 3 months of therapy, computed tomography scans showed the onset
      of osteosclerotic lesions and a significant reduction in all the previously
      identified metastases; on the contrary, a fluorine-18-fluorodeoxyglucose PET
      showed the normalization of fluorine-18-fluorodeoxyglucose uptake in all the
      baseline lesions, including bone metastases. Osteoblastic response, consisting of
      occurrence of new osteoblastic lesions on computed tomography imaging, as a
      consequence of an osteoblastic reaction of previously undetectable bone
      metastases, has been reported in some cancers that receive treatments such as
      chemotherapy, hormonal or targeted therapy. However, it had never been reported
      in patients with melanoma treated with immunotherapy. An apparent worsening of
      bone imaging on standard computed tomography scan in patients under checkpoint
      inhibitor should not lead to modification of treatment strategy, because
      misinterpretation as disease progression may lead to the premature cessation of a
      beneficial treatment and finally have a negative effect on patients' clinical
      outcome.

PMID- 30095444
TI  - AMBU(r) LMA(r) in Children With Cleft Palate for Ophthalmic Surgery: A Case
      Report.
AB  - Airway management remains a challenge in children, and the presence of a cleft
      palate further complicates the scenario. Endotracheal intubation, although
      definitive and most preferred, may be avoided for certain short-duration
      procedures wherein the use of laryngeal mask airway can allow quicker emergence.
      We present the successful airway management of 2 pediatric patients with cleft
      palate undergoing ophthalmological surgery, using AMBU LMA as the airway device
      of choice, which was further used as a rescue airway device in an emergent
      situation of "difficult to ventilate."

PMID- 30095445
TI  - Use of Dexmedetomidine in a Parturient With Multiple Endocrine Neoplasia Type 2A
      Undergoing Adrenalectomy and Thyroidectomy: A Case Report.
AB  - Dexmedetomidine is a selective alpha2-agonist, frequently used in perioperative
      medicine as anesthesia adjunct. The medication carries a Food and Drug
      Administration pregnancy category C designation and is therefore rarely used for
      parturients undergoing nonobstetric surgery. We are reporting the use of
      dexmedetomidine in the anesthetic management of a parturient undergoing minimally
      invasive unilateral adrenalectomy for pheochromocytoma during the second
      trimester of pregnancy. Additionally, because of the multiple endocrine neoplasia
      type 2A constellation with diagnosis of medullary thyroid cancer, the patient
      underwent a total thyroidectomy 1 week after the adrenalectomy.

PMID- 30095446
TI  - Pain Control in a Pediatric Patient With Sickle Cell Disease Using Regional Nerve
      Blocks for Laparoscopic Cholecystectomy: A Case Report.
AB  - The sickle cell patient population continues to provide challenges in pain
      control. Current therapies include narcotic usage with adjuvant therapies such as
      anti-inflammatories and nonpharmacological interventions. Poor pain management in
      the sickle cell patient population, especially postoperatively, can lead to
      hypoventilation, escalating opioid requirements, poor recovery, and longer
      hospital stays. This case report addresses a novel addition of ultrasound-guided
      paravertebral and rectus sheath blocks postinduction of general anesthesia and
      before surgical incision to assist with the intravenous postoperative pain
      management regimen after laparoscopic cholecystectomy in a 10-year-old boy with
      sickle cell disease.

PMID- 30095448
TI  - Individual and Environmental Determinants of Late-Life Community Disability for
      Persons Aging With Cardiovascular Disease.
AB  - OBJECTIVE: To estimate the prevalence of late-life community disability for
      adults aged 65 and older with cardiovascular disease vs. those without. This
      study also investigated the contributions of environmental and individual risk
      factors on late-life community disability for persons with cardiovascular
      disease. DESIGN: Secondary data analysis of the 2016 round of the National Health
      and Aging Trends Study. The study sample included community-dwelling Americans
      with cardiovascular disease (n=1,490) and without (n=4,819). Logistic regression
      was used to estimate associations between individual risk factors, environmental
      factors, and community disability for those with CVD. RESULTS: Individuals with
      cardiovascular disease had a significantly higher prevalence of late-life
      community disability than those without (44.8% vs. 29.0%). For persons with CVD,
      lack of transportation, home modification, and needing assistance with mobility
      increased the odds of community disability. Younger age and lower comorbidity
      were associated with decreased odds of community disability. When accounting for
      environmental factors in multivariate analyses, sex, race, and education were not
      significantly associated with community disability. CONCLUSION: Late-life
      community disability is highly prevalent for persons aging with cardiovascular
      disease. Intervention strategies to deter late-life community disablement should
      focus on improving access to transportation and improving the community
      environment in which older adults live.

PMID- 30095447
TI  - Intraoperative Generalized Tonic-Clonic Seizure and Consequent Severe Brain Bulge
      During Functional Motor Cortex Mapping: A Case Report.
AB  - Intraoperative cortical and subcortical bipolar or monopolar mapping is the gold
      standard for neurosurgical procedures that involve lesions near functional or
      "eloquent" cortex. However, the classic Penfield stimulation has a higher
      intraoperative seizure rate than high-frequency short-train stimulation. As a
      result, high-frequency monopolar stimulation is now the most widely practiced
      technique. However, seizure-free mapping cannot be guaranteed even with high
      frequency stimulation particularly at high current thresholds. We encountered a
      case of severe generalized tonic-clonic seizure and consequent severe brain bulge
      in an 8-year-old child during cortical mapping with the high-frequency protocol.

PMID- 30095449
TI  - San Juan Bautista School of Medicine's Experience in the Aftermath of Hurricane
      Maria.
AB  - The San Juan Bautista School of Medicine (SJBSM) is located in Caguas, Puerto
      Rico. On September 20, 2017, Hurricane Maria hit the island, making landfall as a
      Category 4 storm. The extreme wind force and rainfall caused extensive power
      outages and other damage. In this Invited Commentary, the authors discuss SJBSM's
      actions and lessons learned in the aftermath of Hurricane Maria.By September 25,
      SJBSM had contacted students to ensure their safety and identify their immediate
      needs. The medical school's primary goal was to restore services as expeditiously
      as possible. By October 9, SJBSM had reopened and adjusted its offerings and
      practices to accommodate students' needs. The medical school worked to support
      students' emotional and physical well-being as well as meet their academic needs.
      First- and second-year students who could not be present received recorded
      lectures, study guides, assessments, and other materials electronically or via
      hard copy. Third- and fourth-year students were authorized to complete a single
      clerkship rotation at another medical school in the United States. During this
      time, SJBSM consulted with the Association of American Medical Colleges, the
      Liaison Committee on Medical Education, and other academic agencies. These groups
      offered advice on how to proceed given the hardships the medical school
      faced.Since then, SJBSM has applied lessons learned from Hurricane Maria and
      taken measures to ensure that it can meet the needs of faculty, staff, and
      students in the immediate aftermath of future disasters.

PMID- 30095450
TI  - Going Up? Tips for the Medical Educator's "Elevator Pitch".

PMID- 30095451
TI  - A Randomized Controlled Trial of a Video-Enhanced Advanced Airway Curriculum for
      Pediatric Residents.
AB  - PURPOSE: Pediatric advanced airway management is a low-frequency but critical
      procedure, making it challenging for trainees to learn. This study examined the
      impact of a curriculum integrating prerecorded videos of patient endotracheal
      intubations on performance related to simulated pediatric intubation. METHOD: The
      authors conducted a randomized controlled educational trial for pediatric
      residents between January 2015 and June 2016 at Boston Children's Hospital.
      Investigators collecting data were blinded to the intervention. The control group
      received a standard didactic curriculum including still images, followed by
      simulation on airway trainers. The intervention group received a video-enhanced
      didactic curriculum including deidentified intubation clips recorded using a
      videolaryngoscope, followed by simulation. The study assessed intubation skills
      on simulated infant and pediatric airway scenarios of varying difficulty
      immediately after instruction and at three months. RESULTS: Forty-nine trainees
      completed the curriculum: 23 received the video-enhanced curriculum and 26
      received the standard curriculum. Median time to successful intubation was 18.5
      and 22 seconds in the video-enhanced and standard groups, respectively.
      Controlling for mannequin age and difficulty, residents receiving the video
      enhanced curriculum successfully intubated faster (hazard ratio [95% confidence
      interval]: 1.65 [1.25, 2.19]). Video-enhanced curriculum participants also
      demonstrated decreased odds of requiring multiple attempts and of esophageal
      intubation. At three-month follow-up, residents who received the video-enhanced
      curriculum remained faster at intubation (hazard ratio [95% confidence interval]:
      1.93 [1.23, 3.02]). CONCLUSIONS: Integrating videos of patient intubations into
      an airway management curriculum improved participating pediatric residents'
      intubation performance on airway trainers with sustained improvement at three
      months.

PMID- 30095452
TI  - Remooring: A Qualitative Focus Group Exploration of How Educators Maintain
      Identity in a Sea of Competing Demands.
AB  - PURPOSE: Longitudinal faculty development programs (LFDPs) are communities of
      practice (CoPs) that support development of participants' educator identity
      (EID). This study explored how program graduates negotiated their newly formed
      EIDs among competing identities and demands in academic medicine. METHOD: In this
      multicenter, cross-sectional, qualitative study, graduates of two LFDP cohorts
      (one and five years post-graduation) were invited in 2015 to participate in a one
      hour, cohort-specific focus group. The focus group included questions about
      graduates' views of themselves as educators, their experiences of transition out
      of the LFDP, and sustainability of their EID following program participation.
      Researchers analyzed transcripts using Wenger's CoP and Takfel's social identity
      theories to guide interpretation of findings. RESULTS: Thirty-seven graduates, 17
      from one-year and 20 from five-year post-graduation, participated in eight focus
      groups. They described developing a new EID in their LFDP CoPs. Three major
      themes emerged: context, agency, and identity. A push-pull relationship among
      these themes influenced faculty member's EID trajectory over time. Graduates
      described feeling unmoored from their LFDP community after graduation and relied
      on individual agency to remoor their new identities to supports in the larger
      institutional context. CONCLUSIONS: LFDP graduation represented a transition
      point. Graduates found it challenging to lose supports they had within their time
      limited CoP and remoor their EIDs to workplace supports. Remooring required
      individual agency and external support and affirmation. Faculty development
      programs must be designed with transition periods and sustainability in mind to
      ensure that participants and institutions can benefit from their transformative
      effects over time.

PMID- 30095453
TI  - Health Information Counselors: A New Profession for the Age of Big Data.
AB  - Health care is increasingly data-driven. Concurrently, there are growing concerns
      that health professionals lack the time and training to guide patients through
      the growing medical "data jungle." In the age of big data, ever wider domains of
      people's lives are "datafied," which renders ever more information-at least in
      principle-usable for health care purposes. Turning data into meaningful
      information for clinical practice-and deciding what data or information should
      not be used for this purpose-requires a significant amount of time, resources,
      and skill. The authors argue that academic medicine should lead the way in
      navigating the use of complex, highly personal data in clinical practice. In
      order to make data actionable for both clinicians and patients, the authors
      propose that the best way to navigate the interface between patients and
      providers in the era of data-rich medicine would be the creation of a new
      profession entirely: health information counselors (HICs). HICs would have a
      broad knowledge of various kinds of health data and data quality evaluation
      techniques, as well as analytic skills in statistics and data interpretation.
      Trained also in interpersonal communication, health management, insurance
      systems, and medico-legal aspects of data privacy, HICs would know enough about
      clinical medicine to advise on the relevance of any kind of data for prevention,
      diagnosis, and treatment. The creation of this new specialty would help patients
      and health care professionals to make more informed choices about how increasing
      amounts of health data and information can or should inform health care.This is
      an open-access article distributed under the terms of the Creative Commons
      Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is
      permissible to download and share the work provided it is properly cited. The
      work cannot be changed in any way or used commercially without permission from
      the journal.

PMID- 30095454
TI  - Barriers and Enablers to Direct Observation of Trainees' Clinical Performance: A
      Qualitative Study Using the Theoretical Domains Framework.
AB  - PURPOSE: Direct observation is essential to assess and provide feedback to
      medical trainees. However, calls for its increased use in medical training
      persist as learners report that direct observation occurs infrequently. This
      study applied a theory-driven approach to systematically investigate barriers and
      enablers to direct observation in residency training. METHOD: From September 2016
      to July 2017, semi-structured interviews of faculty and residents at The Ottawa
      Hospital were conducted and analyzed. An interview guide based on the Theoretical
      Domains Framework (TDF) was used to capture 14 domains that may influence direct
      observation. Interview transcripts were independently coded using direct content
      analysis, and specific beliefs were generated by grouping similar responses.
      Relevant domains were identified based on the frequencies of beliefs reported,
      presence of conflicting beliefs, and perceived influence on direct observation
      practices. RESULTS: Twenty-five interviews (12 resident, 13 faculty) were
      conducted, representing 10 specialties. Ten TDF domains were identified as
      influencing direct observation: knowledge, skills, beliefs about consequences,
      social/professional role and identity, intention, goals,
      memory/attention/decision processes, environmental context and resources, social
      influences, and behavioral regulation. Discord between faculty and resident
      intentions, coupled with social expectations that residents should be responsible
      for ensuring that observations occur, was identified as a key barrier.
      Additionally, competing demands identified across multiple TDF domains emerged as
      a pervasive theme. CONCLUSIONS: This study identified key barriers and enablers
      to direct observation. These influencing factors provide a basis for the
      development of potential strategies aimed at embedding direct observation as a
      routine pedagogical practice in residency training.

PMID- 30095455
TI  - Are Teaching Hospitals Treated Fairly in the Hospital-Acquired Condition
      Reduction Program?
AB  - PURPOSE: To identify the factors associated with total Hospital-Acquired
      Condition Reduction Program (HACRP) score and with receiving a Centers for
      Medicare and Medicaid Services (CMS) penalty (1% reduction in payment to those
      hospitals in the lowest-performing quartile of HACRP scores) for fiscal years
      (FYs) 2015-2017 with a particular focus on trends over this period. METHOD: The
      authors evaluated the following variables: (1) type of hospital (teaching vs.
      nonteaching); (2) disproportionate patient percentage; (3) case mix index (CMI);
      (4) number of staffed beds; (5) length of stay (LOS); (6) gross patient revenue;
      and (7) region, using data from CMS and the American Hospital Directory. They
      conducted multivariate linear and logistic regressions. RESULTS: A total of 2,249
      hospitals were included. The mean total HACRP scores across hospitals for FY15,
      FY16, and FY17 were 5.38, 5.35, and 5.18, respectively. In FY15, 21.2%
      (476/2,249) of hospitals received a penalty compared with 22.6% (508/2,249) in
      FY16 and 31.3% (704/2,249) in FY17 (P < .001). The logistic regression model
      showed that teaching hospitals, larger hospitals (> 400 beds), hospitals with
      high CMI or long LOS, and hospitals in the Northeast and Western United States
      were more likely to receive a penalty. Teaching hospitals and larger hospitals
      did not improve their scores over time compared with nonteaching and small
      hospitals. CONCLUSIONS: A reevaluation of the scoring methodology for the HACRP
      is needed. CMS could stratify hospitals into homogeneous categories and apply
      penalties to those that have the worst scores in each category.

PMID- 30095456
TI  - Mentorship Is Not Enough: Exploring Sponsorship and Its Role in Career
      Advancement in Academic Medicine.
AB  - PURPOSE: To understand how sponsorship functions as a professional relationship
      in academic medicine. METHOD: The authors conducted semi-structured interviews
      with Johns Hopkins University School of Medicine faculty in 2016: department
      chairs (sponsors) and faculty participants of an executive leadership development
      program (proteges). Using editing analysis style, the authors coded interview
      transcripts for thematic content; a coding framework and themes were derived
      using an iterative process. RESULTS: Five themes were identified from 23 faculty
      interviews (12 sponsors, 11 proteges): (1) Mentorship is different: Sponsorship
      is episodic and focused on specific opportunities; (2) Effective sponsors are
      career-established and well-connected talent scouts; (3) Effective proteges rise
      to the task and remain loyal; (4) Trust, respect, and weighing risks are key to
      successful sponsorship relationships; (5) Sponsorship is critical to career
      advancement. Sponsorship is distinct from mentorship, though mentors can be
      sponsors if highly placed and well connected. Effective sponsors have access to
      networks and provide unequivocal support when promoting proteges. Effective
      proteges demonstrate potential and make the most of career-advancing
      opportunities. Successful sponsorship relationships are based on trust, respect,
      mutual benefits, and understanding potential risks. Sponsorship is critical to
      advance to high-level leadership roles. Women are perceived as being less likely
      to seek sponsorship but as needing the extra support sponsorship provides to be
      successful. CONCLUSIONS: Sponsorship, in addition to mentorship, is critical for
      successful career advancement. Understanding sponsorship as a distinct
      professional relationship may help faculty and academic leaders make more
      informed decisions about using sponsorship as a deliberate career-advancement
      strategy.

PMID- 30095457
TI  - CD31 Immunohistochemical Expression in Tumors.

PMID- 30095458
TI  - Beneficial Effect of Heat-induced Antigen Retrieval in Immunocytochemical
      Detection of Intracellular Antigens in Alcohol-fixed Cell Samples.
AB  - Immunohistochemistry and immunocytochemistry (ICC) play an irreplaceable role in
      research and diagnostics. It is well known that antigen retrieval (AR) can, as a
      technique, have beneficial outcomes on immunohistochemistry results when using
      formalin-fixed, paraffin-embedded tissue samples. The main purpose of AR is to
      break protein crosslinks which are formed during formalin fixation. Although AR
      was originally designed for formalin-fixed, paraffin-embedded samples, the
      usefulness of AR in ICC has been described in previous studies. Cytologic samples
      are often fixed in alcohol-based fixatives which does not lead to the formation
      of crosslinks. Therefore, alcohol-fixed samples can be successfully immunostained
      without AR. We investigated the effect of heat-induced antigen retrieval (HIAR)
      on alcohol-fixed HEK293 cell line samples and patient cytologic samples from
      thyroid gland obtained by fine needle aspiration technique. We compared indirect
      2-step ICC staining results performed according to the protocol with or without
      HIAR in citrate buffer pH 6 for several antibodies. Utilizing HIAR against
      intracellular antigens has beneficial effects. Therefore, more diluted antibodies
      can be used for satisfactory results. However, surface antigens were probably
      damaged by HIAR treatment. We demonstrated evident changes in cell surface
      topography after HIAR treatment by atomic force microscopy. Staining specificity
      of patient samples improves and background staining is reduced, allowing higher
      dilutions of primary antibody. Improving staining specificity is necessary for
      accurate diagnostics. Although we have shown the beneficial effect of HIAR for
      immunostaining intracellular antigens, proper staining protocol should be tested
      on appropriate controls for individual antibodies.

PMID- 30095459
TI  - Immunohistochemistry in the Detection of Early Myocardial Infarction: Systematic
      Review and Analysis of Limitations Because of Autolysis and Putrefaction.
AB  - The postmortem diagnosis of acute myocardial infarction is one of the main
      problems in forensic practice, especially in cases in which death occurs soon
      after (from minutes to a few hours) the onset of the ischemic damage. Several
      authors have highlighted the possibility to overcome the limits of conventional
      histology in this diagnosis by utilizing immunohistochemistry. In the present
      research, we examined over 30 scientific studies and picked out over 20 main
      immunohistochemical antigens analyzed with a view to enabling the rapid diagnosis
      of early myocardial infarction. The aim of our review was to examine and
      summarize all the principal markers studied to date and also to consider their
      limitations, including protein alteration because of cadaveric autolysis and
      putrefaction.

PMID- 30095460
TI  - APOBEC3B High Expression in Gastroenteropancreatic Neuroendocrine Neoplasms and
      Association With Lymph Metastasis.
AB  - PURPOSE: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B
      (APOBEC3B) is known as a source of mutations in multiple cancers.
      Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a group of
      heterogeneous tumors. However, the expression and significance of APOBEC3B in GEP
      NENs remains unclear. MATERIALS AND METHODS: A total of 158 cases of GEP-NENs,
      including 78 cases of biopsy or endoscopic submucosal dissection resection
      specimens and 83 cases of surgical resection specimens were collected in this
      study. The cases were grouped according to tumor classification grade, including
      42 cases of neuroendocrine tumors G1 (NET G1), 36 cases of NET G2, 36 cases of
      NET G3, 44 cases of neuroendocrine carcinoma (NEC). All of the 158 tumors were
      immunohistochemically studied using a polyclonal antibody against APOBEC3B. We
      evaluated APOBEC3B expression in GEP-NENs and investigated the relationships
      among the immunoreactivity of APOBEC3B, clinical and pathologic features, such as
      age, sex, tumor site, Ki67 cell proliferation index, and lymph metastasis.
      RESULTS: A total of 33 cases (78.6%) of NET G1 showed high expression of
      APOBEC3B. A total of 28 cases (77.8%) of NET G2 demonstrated high expression of
      APOBEC3B. In NET G3 and NEC cases, the positive rates were 52.8% and 2.3%,
      respectively. The expression of APOBEC3B in NETs was significantly higher than
      that in NECs, NET G1 and NET G2 were higher than NET G3, and the difference was
      statistically significant. APOBEC3B high expression cases have lower lymph node
      metastasis rate, lower Ki67 cell proliferation index. CONCLUSIONS: In this study,
      APOBEC3B is highly expressed in GEP-NETs and is a predictor of lymph node
      metastasis in NET G3 and NEC cases. These findings might provide new insights
      into the biological mechanisms of GEP-NENs tumorigenesis and progression.

PMID- 30095461
TI  - Lepidic, Papillary Components and EGFR Mutations are Frequent in Patients With
      Lung Adenocarcinoma Who are Over 75 Years Old.
AB  - Treatment for lung adenocarcinoma frequently diverges from standard treatment in
      older patients. Clinical, pathologic, and molecular characteristics of lung
      cancer in patients over 75 years old have not been fully described. The aim of
      our work was to describe the rate of EGFR, KRAS, BRAF, and HER2 mutations, and
      ALK rearrangement and pathologic characteristics in patients with lung
      adenocarcinoma over 75, compared with patients below 75 years old. This is a
      retrospective study from 2 cohorts: a histopathologic cohort of all consecutively
      resected lung adenocarcinoma in our institution for patients over 75 (n=54, from
      2006 to 2017) compared with patients below 75 years old (n=148, from 2014 to
      2017) and a molecular cohort of all stage IIIb or IV lung adenocarcinoma from
      2009 to 2017 (n=1611). Papillary and lepidic components were more frequently
      found in patients over 75 years old (P=0.046 and 0.0078, respectively). The rate
      of current smokers was lower in older patients (P<0.0001). EGFR mutations were
      more frequent in patients over 75 than in younger patients: 17% versus 8.1%
      (P<0.0001). The mutually exclusive KRAS mutation was more frequent in patients
      below 75 years old than in older patients: 25.8% versus 12.8% (P<0.0001). There
      was no difference for the proportion of the 2 most frequent EGFR mutations (exon
      19 deletion and L858R mutation) (P=0.85) or KRAS-mutated codon (P=0.22) between
      tumors in younger or older patients. There was no statistically significant
      difference for the presence of BRAF, HER2 mutations, and ALK rearrangement
      (P=0.44, 0.71, and 1, respectively). Our work highlights the fact that EGFR
      mutations are more frequent in patients over 75 years old in our population. We
      can hypothesize that this difference might be mainly caused by the less frequent
      occurrence of tobacco-smoking-related lung cancers in the elderly and the
      presence of a lepidic or papillary component in this age group.

PMID- 30095462
TI  - Paraffin Immunofluorescence: A Role Beyond Kidney Biopsies.
AB  - Paraffin immunofluorescence is a well established "salvage" technique in renal
      pathology when representative glomeruli are not found in the fresh frozen tissue
      sent for routine direct immunofluorescence studies. A step of enzymatic digestion
      of the formalin-fixed paraffin-embedded biopsy exposes the antigenic immune
      complexes and allows staining with fluorochrome-tagged antibodies. We explored
      the utility of the technique of paraffin immunofluorescence outside the kidney in
      certain specific scenarios including extra renal amyloid and duodenal
      macroglobulinemia.

PMID- 30095463
TI  - Detection of mRNA of Telomerase Protein in Benign Naevi and Melanomas Using
      RNAscope.
AB  - Telomerase is reactivated in most cancers and is possibly an early driver event
      in melanoma. Our aim was to test a novel in situ hybridization technique,
      RNAscope, for the detection of human telomerase reverse transcriptase (hTERT)
      mRNA in archival formalin-fixed, paraffin-embedded (FFPE) tissue and to compare
      the mRNA expression of melanomas and benign naevi. Furthermore, we wanted to see
      if hTERT mRNA could be a diagnostic or prognostic marker of melanoma. In situ
      hybridization for the detection of hTERT mRNA was performed on FFPE tissue of 17
      melanomas and 13 benign naevi. We found a significant difference in the
      expression of hTERT mRNA between melanomas and benign naevi (P<0.001) and the
      expression of hTERT mRNA correlated with Breslow thickness (rho=0.56, P=0.0205)
      and the Ki67 proliferation index (rho=0.72, P=0.001). This study showed that
      RNAscope was a reliable in situ hybridization method for the detection of hTERT
      mRNA in FFPE tissue of melanomas and benign naevi. hTERT mRNA was more abundantly
      expressed in melanomas compared with benign naevi, but cannot be used solely as a
      diagnostic marker due to an overlap in expression. The hTERT mRNA expression in
      melanomas correlated with the prognostic markers Breslow thickness and the Ki67
      index indicating a prognostic potential of hTERT mRNA.This is an open-access
      article distributed under the terms of the Creative Commons Attribution-Non
      Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to
      download and share the work provided it is properly cited. The work cannot be
      changed in any way or used commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 30095464
TI  - Correlating Changes in the Epithelial Gland Tissue With Advancing Colorectal
      Cancer Histologic Grade, Using IHC Stained for AIB1 Expression Biopsy Material.
AB  - OBJECTIVE: The objective of this study was to study the textural and color
      changes occurring in the epithelial gland tissue with advancing colorectal cancer
      (CRC), utilizing immunohistochemical stain for AIB1 expression biopsy material.
      MATERIAL AND METHODS: Clinical material comprised biopsy specimens of 67 patients
      with a diagnosis of CRC. Two experienced pathologists used H&E-stained material
      for grading CRC lesions and immunohistochemical (IHC) stain for AIB1 expression.
      Twenty six patients were diagnosed with grade I, 28 with grade II, and 13 with
      grade III CRC. Guided by pathologists, we selected the regions of interest from
      AIB1-digitized images of each patient, encompassing the epithelial gland, and we
      computed 69 features, quantifying textural and color properties of the AIB1
      stained lesions. We evaluated the statistical differences between grades by means
      of the Wilcoxon statistical test for each feature, and we assessed changes in
      feature values with advancing tumor grade by means of the Point Biserial
      Correlation. RESULTS: Statistical analysis revealed 14 single features,
      quantifying textural and color properties of the epithelial gland, which
      sustained statistically significant differences between LG-CRC and HG-CRC cases.
      These features were drawn from the gray-level image histogram, the cooccurrence
      matrix, the run length matrix, the discrete wavelet transform, the Tamura method,
      and the L*a*b color transform. CONCLUSIONS: A systematic statistical analysis of
      AIB1-stained biopsy material showed that high-grade CRC lesions contain higher
      intensity levels, appear coarser, are more homogeneous with smooth variation
      across the image, have lower contrast that is slowly varying across the image,
      have lower AIB1 staining, and have lower edges. A combination of textural and
      color attributes, evaluating image gray-tone distribution, textural roughness,
      inhomogeneity, AIB1 staining, and image coarseness should be considered in
      evaluating AIB1-stained CRC lesions.

PMID- 30095465
TI  - Evaluation of Cyclin D1 as a Discriminatory Immunohistochemical Biomarker for
      Idiopathic Pulmonary Fibrosis.
AB  - BACKGROUND: Distinction of idiopathic pulmonary fibrosis (IPF) from other chronic
      fibrosing interstitial pneumonitides, such as hypersensitivity pneumonitis (HP)
      and connective tissue diseases, is critical due to varied biological and clinical
      outcomes. However, their histologic overlaps often pose diagnostic challenges. A
      recent study suggested an association of herpesvirus saimiri infection with IPF.
      Productive viral infection is associated with coexpression of pirated mammalian
      protein cyclin D1, shown to be overexpressed by immunohistochemistry (IHC) in the
      regenerating alveolar epithelium in IPF but not in normal lungs. We evaluated the
      diagnostic utility of cyclin D1 to discriminate between IPF and other fibrosing
      interstitial lung diseases. MATERIALS AND METHODS: A retrospective study of
      cyclin D1 IHC expression in 27 consecutive cases of chronic fibrosing
      interstitial lung diseases from 2011 to 2017: 12 usual interstitial pneumonia
      (UIP) pattern; 5 nonspecific interstitial pneumonia pattern; 3 HP pattern; 7
      unclassifiable was performed. Five cases of normal lung obtained from lobectomy
      specimen for malignancy are included as control. Immunoreactivity was graded
      semiquantitatively on a scale of 0 to 3. RESULTS: Cyclin D1 staining was
      uniformly strongly positive in all cases evaluated in the study, particularly in
      proliferating type II pneumocytes in the region of fibrosing areas. There was no
      statistical difference in the extent of cyclin D1 expression between UIP and non
      UIP groups (2.7 vs. 2.5) and IPF versus non-IPF groups (2.7 vs. 2.4). Cyclin D1
      expression is lower in control group compared with UIP groups (1.2 vs. 2.7).
      CONCLUSIONS: Cyclin D1 is not a specific marker of UIP pattern/IPF. The high
      expression of cyclin D1 in lung tissue of fibrosing interstitial pneumonitides
      regardless of etiology most likely correlates with proliferation in type II
      pneumocytes.

PMID- 30095466
TI  - LI-cadherin and CDX2: Useful Markers in Metastatic Gastrointestinal
      Adenocarcinoma Cells in Serous Cavity Effusion.
AB  - OBJECTIVE: The aim of this study was to investigate the expression and
      significance of liver-intestine cadherin (LI-cadherin) and CDX2 (caudal-type
      homeobox transcription factor 2) in cytology specimens of metastatic
      gastrointestinal adenocarcinoma in serous cavity effusion. MATERIALS AND METHODS:
      The serous cavity effusion samples that were suspected of tumor metastasis in the
      last 5 years were made into paraffin-imbedded cell blocks, a total of 180 cases,
      including 97 cases of pleural effusion, 78 cases of ascites, and 5 cases of
      pericardial effusion. The expressions of LI-cadherin and CDX2 were detected by
      immunohistochemical staining in cell blocks and primary tumor tissues;
      thereafter, the specificity and sensitivity were analyzed. RESULTS: The positive
      expressions of LI-cadherin and CDX2 in 63 cases of gastrointestinal
      adenocarcinoma cells were 65.1% (41/63), 61.9% (39/63), respectively. Of 11 cases
      of pancreaticobiliary duct cancers, only one case (9.09%) was weakly positive for
      LI-cadherin and CDX2 expressions, and 107 cases of non-digestive tract cancers
      were all negative. In 57 matched-pair samples of cell blocks and primary
      gastrointestinal adenocarcinoma tissues, the positive expressions of LI-cadherin
      and CDX2 were 64.9% (37/57), 61.4% (35/57), respectively, in cells, and 82.5%
      (47/57), and 77.2% (44/57), respectively, in tissues. Positive correlation was
      observed between the expressions of LI-cadherin and CDX2 in metastatic
      gastrointestinal adenocarcinoma cells (P<0.05). Both LI-cadherin and CDX2
      expressions demonstrated positive correlation in cells with paired cancer tissues
      (P<0.05). The positive expression reached 80.7% with at least one positive marker
      in the total cell samples through combined detection of LI-cadherin and CDX2,
      increased by 15.8% and 19.3% compared with using either of the markers alone.
      CONCLUSIONS: Combined use of LI-cadherin and CDX2 can improve the accuracy in the
      diagnosis of metastatic adenocarcinoma cells in serous cavity effusion and
      provide some bases of histologic origin because of their high sensitivity and
      specificity.

PMID- 30095467
TI  - High Fidelity of Breast Biomarker Metrics: A 10-Year Experience in a Single,
      Large Academic Institution.
AB  - PURPOSE: Recommendations for standardization of breast biomarkers including
      estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth
      factor 2 (HER2) led to the creation of American Society of Clinical Oncology
      (ASCO)/College of American Pathologists (CAP) guidelines to provide continuous
      guidance. Included in these recommendations is the "ongoing assay assessment
      procedures." We report these biomarker metrics as there is a dearth of published
      information on this topic. MATERIALS AND METHODS: ER, PR, and HER2 positivity
      rates of all newly diagnosed, recurrent, and metastatic invasive breast cancers
      on core biopsies, and repeated testing on resection specimen by
      immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH) were
      collected from April 1, 2008 to December 31, 2017. RESULTS: The positivity rates
      of ER, PR, and HER2 over almost 10 years of monitoring showed high fidelity.
      Total ER-positive rate was 83.6% (81.4% to 86.8%), ER+/PR+ was 71.7% (68.6% to
      75.5%), ER+/PR- was 17.6% (11.0% to 15.0%), ER-/PR- was 16.0% (13.5% to 18.2%),
      and ER-/PR+ was 0.6% (0.2% to 1.0%). The HER2-positive rate was 13.7% (10.2% to
      17.4%) including 9.9% (7.3% to 11.9%) by IHC and 3.8% (1.9% to 5.9%) by FISH
      reflexed from IHC 2+ results. FISH amplification rate of HER2 IHC 2+ cases was
      11.0% (5.8% to 19.2%). Annual quality-assurance check for HER2 IHC/FISH percent
      positive and percent negative agreement (as defined by Food and Drug
      Administration) was 96% to 100%. CONCLUSIONS: This longitudinal active assessment
      of 9564 breast biomarker cases shows the achievement of high fidelity of breast
      biomarker results when following the ASCO/CAP guidelines. Continuous monitoring
      of breast biomarkers may minimize assay analytical drift and assure quality
      clinically relevant results.

PMID- 30095468
TI  - Small Biopsies Misclassify up to 35% of PD-L1 Assessments in Advanced Lung Non
      Small Cell Lung Carcinomas.
AB  - Pembrolizumab is an FDA-approved immune-checkpoint (IC) inhibitor that targets
      programmed cell death protein PD-1, and recent phase III trials have demonstrated
      its superiority over chemotherapy in the treatment of patients with advanced non
      small cell lung cancer (NSCLC). Eligibility for treatment with Pembrolizumab is
      based on demonstration of PD-L1 expression on tumoral cells using the approved
      companion test 22C3 PharmDx (Dako). Access to the drug depends on a tumor
      proportion score (TPS) expressing the PD-L1 protein above predetermined cutoffs.
      The scoring interpretation guide requires a minimum of 100 viable cells to be
      considered adequate for evaluation. Recent studies have questioned the adequacy
      of the sampling process when small biopsies are utilized. To further explore this
      concern, the viable tumor area of 426 consecutive NSCLC biopsies and surgical
      excisions submitted for PD-L1 assessment was measured and recorded with
      corresponding PD-L1 expression. About 14.6% of all biopsies measured <2 mm
      creating 2 groups (<2 mm and >=2 mm) whose PD-L1 categories distribution
      [negative (<1%), low expressor (>=1% and <50%), and positive (>=50%)] were
      compared. Results were significantly different between both groups (chi test;
      P=0.0012). To help understand this difference, 1,407,000 in silico simulated
      biopsies of various sizes were performed on 201 numerical tumors created from
      digitalized full sections and analyzed. Not only the same results shown in actual
      biopsies were reproduced, but the model calculated that up to 35% of very small
      biopsies were misclassified including a mixture of false negative and false
      positive results. The percentage decreased to 10% with a threshold of 5 mm. In
      era of precision medicine, appropriate sampling is more than ever critical to
      achieve accurate assessment of the NSCLC PD-L1. Ignored in most clinical trials,
      recording of biopsy size would permit refining data analysis and increase
      predictive accuracy of current and future biomarkers.

PMID- 30095469
TI  - Osteonecrosis After Contralateral in Situ Prophylactic Pinning for a Slipped
      Capital Femoral Epiphysis: A Case Report.
AB  - CASE: We report the case of an 11-year-old girl who developed osteonecrosis of
      the femoral head in the radiographically normal, asymptomatic left hip that had
      been fixed prophylactically in the context of a slipped capital femoral epiphysis
      (SCFE) that had been detected on the contralateral hip. The etiology of the
      osteonecrosis remains unknown. CONCLUSION: This case report demonstrates that
      prophylactic fixation of a radiographically normal, asymptomatic hip in the
      context of an SCFE on the contralateral side has the potential for substantial
      complications. Therefore, the risk of osteonecrosis in the prophylactically
      pinned hip should be carefully considered because this complication may have
      devastating functional consequences.

PMID- 30095470
TI  - Chylous-Related Complications Following Surgical Management of Clavicular
      Fractures: A Report of Two Cases.
AB  - CASE: We treated 2 patients with chylous-related complications following open
      reduction and internal fixation (ORIF) of the clavicle. These complications were
      of unknown etiology; 1 was treated with percutaneous injection of a sclerosing
      agent, while the other was treated with ligation of the thoracic duct.
      CONCLUSION: A chyle leak is more commonly seen with upper gastrointestinal,
      thoracic, and head and neck surgery. This complication potentially carries a
      substantial rate of morbidity. We report the successful management of 2 patients
      with difficult postoperative chylous-related complications following ORIF of the
      clavicle.

PMID- 30095471
TI  - Traumatic Atlanto-Occipital Dissociation and Atlantoaxial Instability:
      Concomitant Ligamentous Injuries without Neurologic Deficit: A Case Report.
AB  - CASE: A 35-year-old man was involved in a motor-vehicle collision and sustained
      multiple thoracoabdominal and extremity injuries. A high injury burden and a
      normal neurologic examination contributed to a delay in diagnosing a ligamentous,
      combined atlanto-occipital dissociation (AOD) and vertical atlantoaxial injury
      (AAI). Additional imaging revealed the combined injury, and the patient underwent
      an occipitocervical fusion. CONCLUSION: To our knowledge, this is the first case
      of a simultaneous traumatic AOD and AAI without fracture in a neurologically
      intact patient. Knowledge of reliable and easily applied radiographic
      relationships is important to expeditiously diagnose potentially lethal yet
      easily overlooked occipitocervical injuries.

PMID- 30095472
TI  - Pacemaker Lead Dislodgement Due to Left Shoulder Dislocation: A Case Report.
AB  - CASE: A 63-year-old man with a cardiac pacemaker presented with a left shoulder
      dislocation. His heart rate was 46 beats per minute, and pacemaker testing
      demonstrated an elevated pacing threshold, a decreased sensing threshold, and
      stable pacemaker lead impedance. Lead dislodgement due to the shoulder
      dislocation was suspected, and the patient underwent repositioning of the lead.
      CONCLUSION: When a patient with a pacemaker dislocates a shoulder, it should be
      confirmed that the heart rate is above the programmed lower rate of the
      pacemaker; electrocardiography should be performed, and the pacing parameters
      should be checked to ensure that pacing failure is not overlooked.

PMID- 30095473
TI  - Correlation Between Postoperative Distribution of Lordosis and Reciprocal
      Progression of Thoracic Kyphosis and Occurrence of Proximal Junctional Kyphosis
      Following Surgery for Adult Spinal Deformity.
AB  - STUDY DESIGN: This was a retrospective cohort study using consecutive patients.
      OBJECTIVES: The objectives of this study were to evaluate the effect of lumbar
      lordosis (LL) construction on postoperative reciprocal progression of thoracic
      kyphosis (TK) and occurrence of proximal junctional kyphosis (PJK) following
      surgery for adult spinal deformity (ASD). SUMMARY OF BACKGROUND DATA: A large
      postoperative TK has been reported as an iatrogenic risk factor for PJK following
      surgery for ASD. Therefore, knowing how to anticipate and regulate postoperative
      reciprocal progression in TK with LL restorative surgery is important to prevent
      PJK. The LL proportion including distribution of the lordosis (lordosis
      distribution index: LDI) in the lower (L4-S1) and upper (L1-L3) arcs has been
      known as important because it alters the distribution of load. However, the
      influence of postoperative LL construction on postoperative reciprocal change in
      TK resulting in PJK is largely unknown. METHODS: Sixty-six consecutive patients
      with ASD treated with LL restorative surgery with a fusion level consistently
      selected from T8-T10 to the pelvis and followed-up for a minimum of 1 year.
      Abnormal PJK was evaluated according to the Boachie-Adjei classification. Roland
      Morris Disability Questionnaire and Oswestry Disability Index were measured at 1
      year after surgery. RESULTS: The prevalence of PJK in the present study was
      33.3%. Outcomes of patients with PJK were significantly worse than in patients
      without PJK, regardless of PJK grade. Postoperative reciprocal progression in TK
      with LL restorative surgery was found. Preoperative risk factors of PJK were
      older age and smaller sacral slope angle. Postoperative risk factors for PJK
      included increased TK and decreased LDI. We found a strong correlation between
      postoperative LDI and reciprocal progression of TK resulting in PJK. CONCLUSIONS:
      Postoperative LDI is crucial to prevent excess reciprocal progression of TK
      resulting in PJK.

PMID- 30095474
TI  - Multiple-Level Lumbar Total Disk Replacement: A Prospective Clinical and
      Radiographic Analysis of Motion Preservation at 24-72 Months.
AB  - BACKGROUND: Recent studies demonstrate the efficacy of lumbar arthroplasty using
      the ProDisc-L. Patients frequently present with multilevel pathology and may be
      candidates for multilevel disk replacement. PURPOSE: To evaluate clinical
      outcomes and sagittal range of motion of operated levels and adjacent lumbar
      motion segments in multiple-level ProDisc-L constructs after 2-6 years follow-up.
      PATIENT SAMPLE: A total of 159 patients underwent adjacent 2-level (n=114), 3
      level (n=41), or 4-level (n=4) lumbar total disk replacement (TDR). STUDY-DESIGN:
      This is a prospective cohort. OUTCOME MEASURES: Clinical measures: Oswestry
      Disability Index and Visual Analog Score of patient satisfaction (VAS-S) and pain
      (VAS-P) data were collected. Radiographic measures: sagittal motion on
      preoperative and postoperative lumbar radiographs at each operative segment and
      adjacent segment. METHODS: Patients were evaluated with radiographic and clinical
      outcomes measures preoperatively, at 6 weeks, 3 months, 6 months, and annually
      for 24-72 months postoperatively. RESULTS: Radiographic: at the motion segment
      adjacent to the TDR, mean preoperative range of motion (ROM) was 8.20+/-2.88
      degrees, compared with 8.40+/-2.4 degrees postoperatively at last follow-up
      (P>0.05). Between the 3 TDR groups, there were no significant differences in ROM
      at any time point except at L5-S1. Across both groups for TDR motion segments,
      the mean preoperative ROM was 10.15+/-2.71 versus 12.30+/-2.25 degrees
      postoperatively (P=0.011) at last follow-up. At L5-S1 mean preoperative motion
      was 7.60+/-3.90 versus 5.81+/-3.1 degrees postoperatively (P=0.60). Clinical: at
      24-72 months postoperatively, all patients had significant reductions in Oswestry
      Disability Index, VAS-P, and VAS-S scores (P<0.05). At up to 72 months of follow
      up, no patient underwent adjacent-level surgery but there were 3 cases of index
      level revision surgery. CONCLUSIONS: Multilevel TDR preserves ROM at the
      individual TDR levels. Most significantly, the nonoperative adjacent level
      maintains its preoperative ROM at 2-6 years postoperatively. At up to 6 years of
      follow-up, there has been no need for revision or adjacent-segment surgery.
      Patients also demonstrate significant improvement in pain and disability at
      latest follow-up.

PMID- 30095475
TI  - Novel systemic drugs in treatment of atopic dermatitis: results from phase II and
      phase III studies published in 2017/2018.
AB  - PURPOSE OF REVIEW: The present review will give an update of recently published
      clinical studies on novel systemic treatment approaches in atopic dermatitis.
      RECENT FINDINGS: Until 2017 immunosuppressive drugs such as cyclosporine had to
      be used in atopic dermatitis when the disease could not sufficiently be treated
      with topical drugs. Several new substances specifically targeting inflammation in
      atopic dermatitis are currently studied. In 2017, dupilumab was approved in the
      United States and in Europe for first-line biologic treatment of moderate to
      severe atopic dermatitis in adults. The antibody blocks a subunit of the
      interleukin (IL)-4 and IL-13 receptor, thus inhibiting effects of two key
      cytokines in type 2 polarized inflammation. In addition to the studies on
      dupilumab recent clinical investigations on the effects on anti-IL-13
      (lebrikizumab, tralokinumab), anti-IL-31 receptor (nemolizumab), anti-IL-22
      (fezakinumab), and on small molecules targeting the histamine-4-receptor (ZPL389)
      and the Janus kinase inhibitor baricitinib have been published as full papers in
      the last 2 years. SUMMARY: A couple of promising novel therapeutical targets have
      recently been investigated and published in clinical trials on atopic dermatitis.

PMID- 30095476
TI  - Cost-effectiveness of Randomized Study of Laparoscopic Versus Open Bilateral
      Inguinal Hernia Repair.
AB  - OBJECTIVE: The aim of this study is to compare the clinical and cost-effective
      outcomes of the open Lichtenstein repair (OL) and laparoscopic trans-abdominal
      preperitoneal (TAPP) repair for bilateral inguinal hernias. SUMMARY BACKGROUND
      DATA: A cost-effective analysis of laparoscopic versus open inguinal hernia
      repair is still not well addressed, especially regarding bilateral hernia.
      METHODS: This is a clinical and cost-effectiveness analysis within a randomized
      prospective study conducted at Sanchinarro University Hospital.Cases of primary,
      reducible bilateral inguinal hernia were included and randomized using a simple
      randomization program.The outcome parameters included surgical and postoperative
      costs, quality adjusted life years (QALY), and incremental cost per QALY gained
      or the incremental cost effectiveness ratio. RESULTS: Between March 2013 and
      January 2017, 165 patients were enrolled in this study (81 of them underwent TAPP
      and 84 OL).The TAPP procedure had less early postoperative pain (P = 0.037), a
      shorter length of stay (P = 0.001), and fewer postoperative complications (P =
      0.002) when compared with the OL approach. The overall cost of TAPP procedure was
      higher compared with the OL cost (1,683.93&OV0556; vs 1192.83&OV0556;, P =
      0.027). The mean QALYs at 1 year for TAPP (0.8094) was higher than that
      associated with OL (0.6765) (P = 0.018). At a willingness-to-pay threshold of
      20,000 &OV0556; and 30,000 &OV0556;, there was a 95.38% and 97.96% probability
      that TAPP was more cost-effective relative to OL. CONCLUSIONS: The TAPP procedure
      for bilateral inguinal hernia appears to be more cost-effective compared with OL.

PMID- 30095477
TI  - Pilot Study to Evaluate the Safety, Feasibility, and Financial Implications of a
      Postoperative Telemedicine Program.
AB  - BACKGROUND: Telemedicine in surgery holds promise for improving access and
      decreasing costs, but its role remains ill-defined. This pilot study was
      performed to investigate the safety, feasibility, and financial implications of
      providing postoperative care using an electronic clinic (eClinic) at a university
      hospital. METHODS: An easy-to-use and secure eClinic platform was constructed in
      Epic (Epic Systems Corporation, Verona, WA). Patients undergoing laparoscopic
      cholecystectomy, appendectomy, and hernia repairs on an adult acute care surgery
      service were enrolled in this program over an 11-month period (March 2017 to
      January 2018). Patients with prolonged hospitalizations (greater than 4 nights),
      perioperative complications, drains, and open wounds were excluded. Demographics,
      clinical outcomes, encounter time, patient satisfaction survey results, and cost
      analysis were compared with the traditional clinic (tClinic) patient population.
      RESULTS: Two hundred thirty-three eligible patients (61% female; mean age 41 +/-
      16 years) were enrolled in this program. Their demographics were no different
      than the tClinic. Frequencies of readmission, reoperation, and emergency
      department visits (2.7%, 0%, and 4.2%, respectively) in the eClinic group were
      also similar to the tClinic group. However, total visit time was significantly
      shorter in the eClinic group (14 vs 145 minutes, P < 0.01). Anonymous surveys
      demonstrated a high degree of satisfaction, with 85% of patients expressing
      desire to utilize the eClinic again. This program enhanced the capacity for new
      visits to tClinic, with a resultant projected increase in additional operative
      cases and revenue for the health care system. CONCLUSIONS: A safe and efficient
      postoperative telemedicine program can be constructed utilizing a widely
      available electronic medical record system, which can improve patient
      satisfaction, optimize throughput, and increase gross charges for the healthcare
      system.

PMID- 30095478
TI  - Research ethics dilemmas in thyroid disease.
AB  - PURPOSE OF REVIEW: Since research ethics dilemmas frequently fall outside the
      purview of the Institutional Review Board (IRB), we present three unique recent
      research ethics cases in thyroidology that demonstrate research ethics dilemmas.
      RECENT FINDINGS: The cases presented raise questions surrounding
      epistemic/scientific integrity, publication ethics, and professional, and
      personal integrity. SUMMARY: Research ethics dilemmas that fall outside the
      purview of the IRB are appropriate for a Research Ethics Consultation, a common
      service in many large academic medical centers.

PMID- 30095479
TI  - Standardization of mesenchymal stromal cell therapy for perianal fistulizing
      Crohn's disease.
AB  - BACKGROUND: Local administration of mesenchymal stromal cells (MSCs) into the
      fistula tract seems to improve patient outcome in perianal fistulas due to
      Crohn's disease (CD). In this paper we propose a standardized and validated
      protocol for the local administration of MSCs for CD perianal fistulas to be able
      to reliably assess efficacy. MATERIALS AND METHODS: A working group consisting of
      gastroenterologists and surgeons with expertise in the treatment of perianal CD
      developed a consensus perianal fistula treatment protocol for local MSC treatment
      of perianal fistulizing CD. The treatment protocol was validated during a trial
      of allogeneic bone marrow-derived MSCs for the treatment of refractory perianal
      Crohn's fistulas. RESULTS: Localization and classification of perianal fistulas
      with MRI and rectoscopy is of crucial importance prior to surgical intervention
      with local therapy administration. Examination under anesthesia is necessary to
      incise and drain abscesses when present. Optimization of medical treatment when
      active luminal CD is present, is the first step before embarking on surgery and
      local therapy administration. In addition, strictures preventing the surgeon from
      adequately performing the surgical procedure have to be endoscopically dilated.
      Curettage of the fistula tract has an important role as long-standing CD perianal
      fistulas close poorly without removal of their epithelial lining. To diminish
      bacterial contamination of the fistula, the internal opening has to be closed.
      The origin of the fistula is the internal opening, therefore, efficacy of MSCs is
      presumably the highest when they are injected into the tissue around the internal
      opening. CONCLUSION: In this article, we propose a standardized method of local
      MSC administration for perianal fistulizing CD. The use of this standardized and
      validated protocol for the administration of local treatment of CD perianal
      fistulas will allow reliable comparison of the efficacy of local therapies in
      future.

PMID- 30095480
TI  - Personalized medicine in diabetic kidney disease: a novel approach to improve
      trial design and patient outcomes.
AB  - PURPOSE OF REVIEW: In the last decade many attempts have been made to reduce the
      high residual risk of end-stage kidney disease and cardiovascular disease in
      patients with diabetic kidney disease by targeting a variety of risk markers.
      Subsequent analyses revealed that the variation in individual drug response to
      the tested interventions partly explains why these trials did not result in
      additional kidney or cardiovascular protection. This review summarizes recent
      insights regarding individual variation in drug response. Additionally, we
      explore novel approaches to incorporate this drug response variability in the
      design of new clinical trials. RECENT FINDINGS: Recent studies suggest that a
      plausible explanation for individual therapy resistance emanates from intrinsic
      individual characteristics such as genetic make-up or volume status and is likely
      only partially explained by drug characteristics such as the dose or type of
      intervention. Biomarker-based enrichment strategies to identify high-risk
      individuals and/or those who are more likely to respond to interventions offer
      opportunities to tailor therapies to individual patients. SUMMARY: Individual
      drug response variability is a recognized phenomenon in clinical practice. It is
      time to implement novel approaches that take into account this response
      variability in the design of new trials in diabetic kidney disease in order to
      define optimal therapies for individual patients.

PMID- 30095481
TI  - Personalized medicine in nephrology: a novel approach or just good medicine?

PMID- 30095482
TI  - The use of (newer) antipsychotics in bipolar inpatients over a 17-year
      observation period.
AB  - Antipsychotics (AP) are commonly used in the treatment of bipolar disorder. They
      cover a broad spectrum of indications including acute psychotic, manic and
      depressive symptoms, and maintenance treatment. This study evaluates the changes
      in prescribing patterns of first-generation antipsychotics (FGA) and second
      generation AP at Innsbruck University Hospital for the treatment of bipolar
      inpatients between 1999 and 2016. In this retrospective chart review, we included
      adult patients with a diagnosis of bipolar affective disorder (ICD 9: F296; ICD
      10: F31) who were admitted as inpatients at the Department for Psychiatry and
      Psychotherapy between 1999 and 2016 for more than 7 days. The study was approved
      by the local ethics committee. The complete medical histories were searched
      retrospectively for the prescription of psychotropic medications at the time of
      discharge, with a special focus on APs. We found a significant increase in the
      use of atypical AP, mainly attributable to the prescription of quetiapine for all
      types of episodes, followed by aripiprazole for manic and as add-on therapy for
      depressive episodes. The prescription rate of clozapine decreased significantly.
      The prescription rate of FGA showed a small but not significant decrease for the
      treatment of manic and mixed episodes, and a significant decrease for depressive
      episodes. These trends apparently mirror in part the evidence base for the use of
      AP, but also illustrate that clinicians still appreciate the effectiveness of FGA
      despite their inferior tolerability profile.

PMID- 30095483
TI  - Postanesthesia care by remote monitoring of vital signs in surgical wards.
AB  - PURPOSE OF REVIEW: This narrative review summarizes recent insights into the role
      of remote monitoring of vital signs in the postoperative period in surgical
      wards. RECENT FINDINGS: Despite recent improvements in the safety of anesthesia
      and surgical procedures, postoperative complication rates are still unacceptably
      high. This is partly attributable to the intermittent provision of personal care
      to patients by nurses and ward physicians. Continuous remote monitoring of vital
      functions in the early postoperative period may reduce these complication rates.
      There are several medical-grade remote monitoring platforms available that
      integrate a biosensor signal with electronic patient records, enabling automated
      prediction or notification of patient deterioration. Most available platforms
      have technical limitations with respect to the accuracy of respiratory rate
      measurements. Of note, although the implementation of automated notifications of
      patient deterioration is associated with a reduced activation of acute response
      teams, the involvement of ward physicians in the early diagnosis and treatment of
      subtle changes in vital functions is increased. SUMMARY: Remote monitoring of
      vital signs in the surgical ward may contribute to prevention of severe
      complications and reduction in failure-to-rescue rates, although evidence for
      this association is still lacking. Anesthesiologists should contribute their
      knowledge and skills with respect to perioperative abnormalities in vital
      functions to improve patient safety during the postoperative period.

PMID- 30095484
TI  - Proprioception 2.0: novel functions for muscle spindles.
AB  - PURPOSE OF REVIEW: Muscle spindles are encapsulated mechanosensory receptors
      within skeletal muscle tissue that inform the central nervous system about the
      contractile status of each muscle. This information is required for any
      coordinated movement and for stable posture. This review summarizes recent
      findings regarding novel functions for proprioceptive feedback information,
      muscle spindle disease and the molecular basis of mechanoreception. RECENT
      FINDINGS: Muscle spindle function is not limited to regulating motor control but
      is also required for appropriate realignment of fractured bones, successful
      regeneration of spinal cord axons after injury and spinal alignment. Several
      proteins responsible for or modulating mechanotransduction in proprioceptive
      sensory neurons have been identified, including the Piezo2 channel as a candidate
      for the principal mechanotransduction channel. Many neuromuscular diseases are
      known to be accompanied by an impaired function of muscle spindles, resulting in
      a decline of motor performance and coordination in the patients. SUMMARY: Our
      knowledge regarding the molecular basis of muscle spindle function is still
      incomplete. However, increasing our understanding of mechanotransduction in
      muscle spindles is a prerequisite for finding appropriate strategies to prevent
      injuries due to unstable gait and frequent falls.

PMID- 30095485
TI  - Congenital Chagas disease: current diagnostics, limitations and future
      perspectives.
AB  - PURPOSE OF REVIEW: Congenital transmission is an important route of Trypanosoma
      cruzi infection, both in Latin America and internationally, with considerable
      populations of infected women of child-bearing age residing in the United States
      and Europe. This review examines recent literature on congenital Chagas disease,
      with a focus on the changing clinical spectrum and potential new diagnostic
      tools. RECENT FINDINGS: Vertical transmission occurs in approximately 5-10% of
      births from T. cruzi-infected mothers. Historically, congenital Chagas disease
      was associated with high levels of neonatal morbidity and mortality. Bolivian
      birth cohort data from the early 1990s to the present indicate that the incidence
      of symptomatic neonatal disease has declined. Treatment with trypanocides is
      greater than 90% effective and well tolerated in infants. Current programs face
      challenges from the multistep screening algorithm, low sensitivity of microscopy
      and high loss to follow-up. SUMMARY: Congenital Chagas disease remains an
      important contributor to the global disease burden because of T. cruzi. PCR and
      related molecular techniques represent the most sensitive diagnostic modalities
      for early detection but require further optimization for resource-limited
      settings. Several novel diagnostic tests show promise for the future but further
      validation and adaptation to field settings are needed.

PMID- 30095486
TI  - Updates on the management of neurocysticercosis.
AB  - PURPOSE OF REVIEW: The goal of this review is highlight recent developments
      regarding neurocysticercosis, including recently developed guidelines. RECENT
      FINDINGS: Recent diagnostic criteria highlight the importance of neuroimaging in
      establishing a diagnosis. Monoclonal antibody-based antigen detection and the
      enzyme-linked immunotransfer blot can be confirmatory. Management should be
      guided by the form of disease. Single enhancing lesions and one to two viable
      parenchymal cysticerci can be treated with short courses of albendazole and
      corticosteroid. Multiple parenchymal lesions should be treated with the
      combination of corticosteroids, albendazole, and praziquantel. Ventricular
      cysticerci should be removed when possible, often by minimally invasive surgery.
      Subarachnoid cysticercosis often requires prolonged courses of antiparasitic and
      anti-inflammatory treatment. SUMMARY: Neurocysticerocis represents a spectrum of
      disease that is a common cause of neurologic disease worldwide. Management needs
      to be guided by the number and location of the parasites and the host response.

PMID- 30095487
TI  - Atrial Fibrillation in Advanced Heart Failure Patients Receiving Left Ventricular
      Assist Devices.

PMID- 30095488
TI  - The role of ultrasound in the evaluation of acute pelvic pain in pregnancy and
      postpartum period: a review.
AB  - PURPOSE OF REVIEW: Acute pelvic pain in pregnant and postpartum patients presents
      diagnostic and therapeutic challenges. Ultrasound remains the primary imaging
      modality of choice for assessing pregnant and postpartum women. The purpose of
      this review is to help practitioners ensure a correct diagnosis of acute pelvic
      pain in pregnancy and the postpartum period. RECENT FINDINGS: This review
      describes the various causes and highlights the sonographic features and
      characteristics of acute pelvic pain in pregnancy and the postpartum period.
      SUMMARY: Evaluation of acute pelvic pain in pregnancy and the postpartum period
      is challenging. Knowledge of the clinical settings and sonographic features of
      acute pelvic pain in pregnancy and the postpartum period can lead to accurate
      diagnosis and appropriate management of the condition.

PMID- 30095489
TI  - Surgical skills assessment tools in gynecology.
AB  - PURPOSE OF REVIEW: The purpose of this review is to outline surgical skills
      assessment tools for the purpose of training and competency evaluation, with a
      focus on recent literature in gynecology. RECENT FINDINGS: Objective standardized
      surgical skills assessment tools are increasingly being explored in multiple
      surgical disciplines including gynecology. Several small studies in gynecology
      have validated procedure-specific checklists, global rating scales, and other
      surgical proficiency examinations in their ability to differentiate trainee skill
      level or correlate with other standardized tests. Few studies have included
      gynecologic surgeons in practice, and no studies have investigated their use in
      credentialing and maintenance of certification. SUMMARY: Surgical skills
      assessment tools may be a useful adjunct to gynecology training programs, with
      promising applications for practicing gynecologists.

PMID- 30095491
TI  - The lung clearance index as a monitoring tool in cystic fibrosis: ready for the
      clinic?
AB  - PURPOSE OF REVIEW: In cystic fibrosis, (CF) there is an urgent need for objective
      tests that can capture and track preclinical lung disease. The lung clearance
      index (LCI), the primary outcome measure of the multiple breath washout test, is
      an established endpoint in clinical trials but the clinical utility of the test
      remains poorly defined. The purpose of this review is to examine the key studies
      over the past years that have advanced our understanding of the role of the LCI
      in clinical practice. RECENT FINDINGS: The variability of LCI measurements
      increases with lung disease severity, and new evidence shows that between-visit
      changes in the LCI are therefore best expressed as a relative rather than an
      absolute change. A relative change of greater than 15% between visits is likely
      outside the intrinsic variability of the test and physiologically relevant. The
      LCI is feasible to perform and is a more sensitive outcome measure than forced
      expiratory volume in one second (FEV1). The LCI correlates with outcome measures
      such as structural MRI, and shows great promise in the routine clinical
      monitoring of CF lung disease, particularly in younger patients with milder
      disease. SUMMARY: Recent studies have progressed our understanding of the role of
      the LCI in clinical practice, but the exact clinical utility of the test in
      monitoring CF lung disease is still uncertain.

PMID- 30095492
TI  - Emerging Gram-negative bacteria: pathogenic or innocent bystanders.
AB  - PURPOSE OF REVIEW: The current review examines the current literature around
      'emerging' Gram-negative bacteria other than Pseudomonas aeruginosa in cystic
      fibrosis (CF), paying particular focus on the recent literature for those that
      are more frequently encountered: Pandoraea, Achromobacter, Ralstonia and
      Stenotrophomonas species. RECENT FINDINGS: The recent literature is evolving our
      understanding of the clinical consequences of infection with an 'emerging' Gram
      negative bacteria in CF. There is an increase in reported prevalence for many
      species. They are commonly isolated from patients who already have low baseline
      lung function. Initial infection can lead to chronic carriage, often with
      evidence of an associated host immune response and subsequent clinical
      deterioration. For some species occasional cases of bacteraemia have been
      reported. SUMMARY: There are a number of Gram-negative organisms, other than P.
      aeruginosa, that can cause chronic infection in patients with CF. There is data
      to suggest that some of these so-called emerging Gram-negative bacteria are
      increasing in prevalence and can be pathogenic in patients with CF. The
      prevalence and clinical consequences however differ from species to species.
      There is a pressing need to agree a definition of chronic infection for these
      organisms to compare data between studies.

PMID- 30095490
TI  - Characterization of Primary Cilia in Normal Fallopian Tube Epithelium and Serous
      Tubal Intraepithelial Carcinoma.
AB  - OBJECTIVES: The aim of this study was to investigate the distribution of primary
      cilia on secretory cells in normal fallopian tube (FT) and serous tubal
      intraepithelial carcinoma (STIC). METHODS: Fallopian tube tissue samples were
      obtained from 4 females undergoing prophylactic hysterectomies and 6 patients
      diagnosed with STIC. A mogp-TAg transgenic mouse STIC sample was also compared
      with a wild-type mouse FT sample. Serous tubal intraepithelial carcinoma was
      identified by hematoxylin and eosin staining and confirmed by positive Ki-67 and
      p53 immunohistochemical staining of tissue sections. We assessed the relative
      distribution of primary cilia on secretory cells and motile cilia on multiple
      ciliated cells by immunofluorescence and immunohistochemical staining. Ciliary
      function was assessed by immunofluorescence staining of specific ciliary marker
      proteins and responsiveness to Sonic Hedgehog signaling. RESULTS: Primary cilia
      are widespread on secretory cells in the ampulla, isthmus, and in particular, the
      fimbriae of human FT where they may appear to mediate ciliary-mediated Sonic
      Hedgehog signaling. A statistically significant reduction in the number of
      primary cilia on secretory cells was observed in human STIC samples compared with
      normal controls (P < 0.0002, Student t test), supported by similar findings in a
      mouse STIC sample. Immunohistochemical staining for dynein axonemal heavy chain 5
      discriminated multiple motile cilia from primary cilia in human FT. CONCLUSIONS:
      Primary cilia are widespread on secretory cells in the ampulla, isthmus, and in
      particular, the fimbriae of the human FT but are significantly reduced in both
      human and mouse STIC samples. Immunohistochemical staining for ciliary proteins
      may have clinical utility for early detection of STIC.

PMID- 30095493
TI  - Spectral Domain Anterior Segment Optical Coherence Tomography in Fungal
      Keratitis.
AB  - PURPOSE: To evaluate the use of spectral domain anterior segment optical
      coherence tomography (SD-ASOCT) in fungal keratitis. METHODS: Fifty eyes of 50
      patients with fungal keratitis were recruited. Serial ASOCT was performed on days
      0, 7, 14, 21, 28, 42, and 56. Corneal thickness (CT) in the infiltrate area,
      infiltrate thickness (IT), and infiltrate width were measured at each follow-up.
      The presence of any specific feature on ASOCT was evaluated. RESULTS: Mean CT and
      IT at presentation were 650.5 +/- 108 MUm and 401.1 +/- 91 MUm, which reduced
      significantly at each follow-up [on days 7, 14, 28, and 42; 626.8 +/- 113 MUm (P
      < 0.001) and 367.3 +/- 94 MUm (P = 0.002), 601.4 +/- 109 MUm and 344.7 +/- 94 MUm
      (P < 0.001), 544.8 +/- 103 MUm and 305.1 +/- 80 MUm (P < 0.001), and 522.8 +/- 97
      MUm and 291.4 +/- 79 MUm (P < 0.001), respectively]. The mean CT and scar depth
      at complete healing were 496.3 +/- 101 MUm and 283.2 +/- 77 MUm, respectively. In
      10/50 (20%) eyes, the posterior border of the cornea was not clearly visible
      because of posterior shadowing; therefore, IT was measured along the maximum
      visible area of hyperreflectivity, whereas CT was measured just adjacent to the
      area of shadowing. The infiltrate width was measured in 35 eyes, and the mean
      values at days 0, 7, 14, 28, 42, and 56 were 5.5 +/- 0.8 mm, 4.6 +/- 0.7 mm, 4.4
      +/- 0.6 mm, 4.2 +/- 0.6 mm, 4.1 +/- 0.6 mm, and 4.1 +/- 0.6 mm, respectively. A
      satellite lesion and endothelial plaque were seen in 30% (15/50) and 44% (22/50)
      eyes, respectively. CONCLUSIONS: ASOCT is a useful adjunct in monitoring fungal
      keratitis especially in cases with deep stromal involvement and endothelial
      plaques. In addition, it also provides insight into the activity of keratitis.

PMID- 30095494
TI  - Viability of Descemet Membrane Endothelial Keratoplasty Grafts Folded in the Eye
      Bank.
AB  - PURPOSE: Preloaded, trifolded grafts in Descemet membrane endothelial
      keratoplasty require transfer of the trifolding process from the corneal
      transplant surgeon to the eye bank technician. We sought to assess whether
      trifolding may be safely conducted by an eye bank technician with cell loss
      comparable to standard peeling and lifting. METHODS: A total of 10 grafts were
      stained, peeled, and transferred directly onto a bed of Calcein-AM and Amvisc
      Plus by an eye bank technician. Five grafts were removed and stained as a scroll,
      and 5 grafts were trifolded with the endothelium in before transfer. Photographs
      were acquired with an inverted fluorescence microscope, and image segmentation
      was performed. A t test was conducted to compare differences in endothelial cell
      loss across groups. RESULTS: Mean cell loss in the scroll group was 18.5% [95%
      confidence interval (CI): 15.2%-21.9%] compared with 7.6% of the trifolded group
      (95% CI: 1.7%-13.5%). A 2-tailed t test indicated decreased cell loss in the
      trifolded group (P = 0.013). CONCLUSIONS: Despite additional manipulation of the
      graft, trifolding of Descemet membrane and endothelium may be performed by an eye
      bank technician without significantly increased cell loss relative to graft
      preparation as a scroll.

PMID- 30095496
TI  - Shoulder Impairment Following Critical Illness: A Prospective Cohort Study.
AB  - OBJECTIVES: Identify the prevalence of shoulder impairment in ICU survivors
      within 6 months of discharge from ICU. Evaluate the impact of shoulder impairment
      on upper limb functional status in patients treated on an ICU. Identify risk
      factors for the development of shoulder impairment. DESIGN: Prospective cohort
      study. SETTING: A tertiary care medical-surgical-trauma ICU at a U.K. hospital
      over 18 months, with a further 6-month follow-up after hospital discharge.
      SUBJECTS: Adult patients with an ICU length of stay of greater than 72 hours with
      no preexisting or new neurologic or traumatic upper limb injury. INTERVENTIONS:
      None. MEASUREMENTS AND MAIN RESULTS: Patients underwent targeted shoulder
      assessments (pain, range of movement, Constant-Murley Score, shortened version of
      the disabilities of the arm, shoulder, and hand [DASH] score [QuickDASH] score)
      at hospital discharge, 3 and 6 months after hospital discharge. Assessments were
      undertaken on 96 patients, with 62 patients attending follow-up at 3 months and
      61 patients at 6 months. Multivariate regression analysis was used to investigate
      risk factors for shoulder impairment. ICU-related shoulder impairment was present
      in 67% of patients at 6 months following discharge from hospital. Upper limb
      dysfunction occurred in 46%, with 16% having severe dysfunction (equivalent to
      shoulder dislocation). We were unable to identify specific risk factors for
      shoulder impairment. CONCLUSIONS: Shoulder impairment is a highly prevalent
      potential source of disability in ICU survivors. This persists at 6 months after
      discharge with a significant impact on upper limb function. More research is
      needed into potential mechanisms underlying shoulder impairment and potential
      targeted interventions to reduce the prevalence.

PMID- 30095497
TI  - Postdischarge Major Adverse Cardiovascular Events of ICU Survivors Who Received
      Acute Renal Replacement Therapy.
AB  - OBJECTIVES: Long-term risk of a major adverse cardiovascular events in ICU
      survivors who underwent acute renal replacement therapy requires further
      investigation. DESIGN: Nationwide population-based study using the claims
      database of Korea. SETTING: Index admission cases of ICU survivors in government
      designated tertiary hospitals PATIENTS:: The study group consisted of ICU
      survivors who underwent acute renal replacement therapy, and the control group
      consisted of those without acute renal replacement therapy. Patients were
      excluded if they 1) were under age 20, 2) expired within 30 days after discharge,
      3) received ICU care for less than 24 hours, 4) had a previous ICU admission, 5)
      had a history of major adverse cardiovascular event, or 6) had a major adverse
      cardiovascular event-related cardio/cerebrovascular diseases. The outcomes of the
      patients who received continuous renal replacement therapy were compared with
      those of patients who received only intermittent renal replacement therapy.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Information regarding patient
      characteristics and treatment modalities was collected and adjusted. The main
      outcome was major adverse cardiovascular event, including acute myocardial
      infarction, revascularization, and acute ischemic stroke. Patient mortality and
      progression to end-stage renal disease were also evaluated. We included 12,380
      acute renal replacement therapy patients and 382,018 patients in the control
      group. Among the study group, 6,891 patients were included in the continuous
      renal replacement therapy group, and 5,034 in the intermittent renal replacement
      therapy group. The risks of major adverse cardiovascular event (adjusted hazard
      ratio, 1.463 [1.323-1.619]; p < 0.001), all-cause mortality (adjusted hazard
      ratio, 1.323 [1.256-1.393]; p < 0.001), and end-stage renal disease (adjusted
      hazard ratio, 18.110 [15.779-20.786]; p < 0.001) were higher in the acute renal
      replacement therapy patients than the control group. When we compared the
      continuous renal replacement therapy patients with the intermittent renal
      replacement therapy patients, the risk of major adverse cardiovascular event was
      comparable (adjusted hazard ratio, 1.049 [0.888-1.239]; p = 0.575). CONCLUSIONS:
      Clinicians should note the increased risk of a long-term major adverse
      cardiovascular event in acute renal replacement therapy patients and consider
      appropriate risk factor management. Significant difference in the risk of
      postdischarge major adverse cardiovascular event was not identified between
      continuous renal replacement therapy and intermittent renal replacement therapy.

PMID- 30095499
TI  - Complication and Failures of Central Vascular Access Device in Adult Critical
      Care Settings.
AB  - OBJECTIVES: To examine the proportion and rate of central venous access device
      failure and complications across central venous access device types in adult
      intensive care. DATA SOURCES: A systematic search was undertaken in the
      electronic databases Cochrane Central Register of Controlled Trials, Embase, U.S.
      National Library of Medicine National Institutes of Health, and Cumulative Index
      to Nursing and Allied Health in September 2017. STUDY SELECTION: Included studies
      were of observational (prospective and retrospective) or interventional design
      and reported central venous access device failure and complications in adult ICU
      settings. Studies were excluded if they were published prior to November 2006 or
      not reported in English. Two reviewers independently screened articles, assessed
      eligibility, extracted data, and assessed risk of bias. DATA EXTRACTION: Data
      were extracted on the primary outcome, central venous access device failure, and
      secondary outcomes: central venous access device complications (central line
      associated bloodstream infection, catheter-related bloodstream infection,
      catheter-related thrombosis, occlusion, catheter removal due to suspected
      infection, dislodgement, breakage, and local infection). Patient and device data
      and study details to assess the study quality were also extracted. DATA
      SYNTHESIS: A total of 63 studies involving 50,000 central venous access devices
      (396,951 catheter days) were included. Central venous access device failure was
      5% (95% CI, 3-6%), with the highest rates and proportion of failure in
      hemodialysis catheters. Overall central line-associated bloodstream infection
      rate was 4.59 per 1,000 catheter days (95% CI, 2.31-6.86), with the highest rate
      in nontunneled central venous access devices. Removal of central venous access
      device due to suspected infection was high (17%; 20.4 per 1,000 catheter days;
      95% CI, 15.7-25.2). CONCLUSIONS: Central venous access device complications and
      device failure is a prevalent and significant problem in the adult ICU, leading
      to substantial patient harm and increased healthcare costs. The high proportion
      of central venous access devices removed due to suspicion of infection, despite
      low overall central line-associated bloodstream infection and catheter-related
      bloodstream infection rates, indicates a need for robust practice guidelines to
      inform decision-making surrounding removal of central venous access devices
      suspected of infection.

PMID- 30095498
TI  - Epidemiology of Cause of Death in Pediatric Acute Respiratory Distress Syndrome.
AB  - OBJECTIVES: Investigations of acute respiratory distress syndrome in adults
      suggest hypoxemia is an uncommon cause of death. However, the epidemiology of
      death in pediatric acute respiratory distress syndrome is not well characterized.
      We aimed to describe the cause, mode, and timing of death in pediatric acute
      respiratory distress syndrome nonsurvivors. We hypothesized that most deaths
      would be due to nonpulmonary factors, rather than hypoxemia. DESIGN:
      Retrospective, decedent-only analysis. SETTING: Two large, academic PICUs.
      PATIENTS: Nonsurvivors with pediatric acute respiratory distress syndrome.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 798 subjects with
      pediatric acute respiratory distress syndrome, there were 153 nonsurvivors (19%
      mortality). Median time to death was 6 days (interquartile range, 3-13 d) after
      pediatric acute respiratory distress syndrome onset. Patients dying less than 7
      days after pediatric acute respiratory distress syndrome onset had greater
      illness severity and worse oxygenation. Patients dying less than 7 days were more
      likely to die of a neurologic cause, including brain death. Patients dying
      greater than or equal to 7 days after pediatric acute respiratory distress
      syndrome onset were more commonly immunocompromised. Multisystem organ failure
      predominated in deaths greater than or equal to 7 days. Withdrawal of therapy was
      the most common mode of death at all timepoints, accounting for 66% of all
      deaths. Organ dysfunction was common at time of death, irrespective of cause of
      death. Refractory hypoxemia accounted for only a minority of pediatric acute
      respiratory distress syndrome deaths (20%). CONCLUSIONS: In pediatric acute
      respiratory distress syndrome, early deaths were due primarily to neurologic
      failure, whereas later deaths were more commonly due to multisystem organ
      failure. Deaths from neurologic causes accounted for a substantial portion of
      nonsurvivors. Refractory hypoxemia accounted for only a minority of deaths. Our
      study highlights limitations associated with using death as an endpoint in
      therapeutic pediatric acute respiratory distress syndrome trials.

PMID- 30095500
TI  - Extracorporeal Membrane Oxygenation Can Successfully Support Patients With Severe
      Acute Respiratory Distress Syndrome in Lieu of Mechanical Ventilation.
AB  - OBJECTIVES: Extracorporeal membrane oxygenation is increasingly used in the
      management of severe acute respiratory distress syndrome. With extracorporeal
      membrane oxygenation, select patients with acute respiratory distress syndrome
      can be managed without mechanical ventilation, sedation, or neuromuscular
      blockade. Published experience with this approach, specifically with attention to
      a patient's respiratory drive following cannulation, is limited. DESIGN: We
      describe our experience with three consecutive patients with severe acute
      respiratory distress syndrome supported with right jugular-femoral configuration
      of venovenous extracorporeal membrane oxygenation without therapeutic
      anticoagulation as an alternative to lung-protective mechanical ventilation.
      Outcomes are reported including daily respiratory rate, vital capacities, and
      follow-up pulmonary function testing. RESULTS: Following cannulation, patients
      were extubated within 24 hours. During extracorporeal membrane oxygenation
      support, all patients were able to maintain a normal respiratory rate and
      experienced steady improvements in vital capacities. Patients received oral
      nutrition and ambulated daily. At follow-up, no patients required supplemental
      oxygen. CONCLUSIONS: Our results suggest that venovenous extracorporeal membrane
      oxygenation can provide a safe and effective alternative to lung-protective
      mechanical ventilation in carefully selected patients. This approach facilitates
      participation in physical therapy and avoids complications associated with
      mechanical ventilation.

PMID- 30095501
TI  - Incidence and Prevalence of Pressure Injuries in Adult Intensive Care Patients: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: To systematically assess the incidence and prevalence of pressure
      injuries in adult ICU patients and the most frequently occurring pressure injury
      sites. DATA SOURCES: MEDLINE, Embase, the Cochrane Library, and Cumulative Index
      to Nursing and Allied Health Literature. STUDY SELECTION: Observational studies
      reporting incidence rates, cumulative incidence, and prevalence of pressure
      injuries. DATA EXTRACTION: Two reviewers independently screened studies,
      extracted data, and assessed the risk of bias. Meta-analyses of pooled weighted
      estimates were calculated using random effect models with 95% CIs reported due to
      high heterogeneity. Sensitivity analyses included studies that used skin
      inspection to identify a pressure injury, studies at low risk of bias, studies
      that excluded stage 1 and each stage of pressure injury. DATA SYNTHESIS: Twenty
      two studies, 10 reporting cumulative incidence of pressure injury irrespective of
      stage, one reporting incidence rate (198/1,000 hospital-days), and 12 reporting
      prevalence were included. The 95% CI of cumulative incidence and prevalence were
      10.0-25.9% and 16.9-23.8%. In studies that used skin inspection to identify
      pressure injuries, the 95% CI of cumulative incidence was 9.4-27.5%; all
      prevalence studies used skin inspection therefore the results were unchanged. In
      studies assessed as low risk of bias, the 95% CI of cumulative incidence and
      prevalence were 6.6-36.8% and 12.2-24.5%. Excluding stage 1, the 95% CI of
      cumulative incidence and prevalence were 0.0-23.8% and 12.4-15.5%. Five studies
      totalling 406 patients reported usable data on location; 95% CI of frequencies of
      PIs were as follows: sacrum 26.9-48.0%, buttocks 4.1-46.4%, heel 18.5-38.9%, hips
      10.9-15.7%, ears 4.3-19.7%, and shoulders 0.0-40.2%. CONCLUSIONS: Although well
      designed studies are needed to ensure the scope of the problem of pressure
      injuries is better understood, it is clear prevention strategies are also
      required.

PMID- 30095503
TI  - Eye Tracking as a Biomarker for Concussion in Children.
AB  - OBJECTIVE: Concussion is the most common type of brain injury in both pediatric
      and adult populations and can potentially result in persistent postconcussion
      symptoms. Objective assessment of physiologic "mild" traumatic brain injury in
      concussion patients remains challenging. This study evaluates an automated eye
      tracking algorithm as a biomarker for concussion as defined by its symptoms and
      the clinical signs of convergence insufficiency and accommodation dysfunction in
      a pediatric population. DESIGN: Cross-sectional case-control study. SETTING:
      Primary care. PATIENTS: Concussed children (N = 56; mean age = 13 years),
      evaluated at a mean of 22-week post-injury, compared with 83 uninjured controls.
      INDEPENDENT VARIABLES: Metrics comparing velocity and conjugacy of eye movements
      over time were obtained and were compared with the correlation between Acute
      Concussion Evaluation (ACE) scores, convergence, and accommodation dysfunction.
      MAIN OUTCOME MEASURES: Subjects' eye movements recorded with an automated eye
      tracker while they watched a 220-second cartoon film clip played continuously
      while moving within an aperture. RESULTS: Twelve eye-tracking metrics were
      significantly different between concussed and nonconcussed children. A model to
      classify concussion as diagnosed by its symptoms assessed using the ACE achieved
      an area under the curve (AUC) = 0.854 (71.9% sensitivity, 84.4% specificity, a
      cross-validated AUC = 0.789). An eye-tracking model built to identify near point
      of convergence (NPC) disability achieved 95.8% specificity and 57.1% sensitivity
      for an AUC = 0.810. Reduced binocular amplitude of accommodation had a Spearman
      correlation of 0.752(P value <0.001) with NPC. CONCLUSION: Eye tracking
      correlated with concussion symptoms and detected convergence and accommodative
      abnormalities associated with concussion in the pediatric population. It
      demonstrates utility as a rapid, objective, noninvasive aid in the diagnosis of
      concussion.

PMID- 30095502
TI  - Early Right Ventricular Systolic Dysfunction and Pulmonary Hypertension Are
      Associated With Worse Outcomes in Pediatric Acute Respiratory Distress Syndrome.
AB  - OBJECTIVES: The prevalence and importance of early right ventricular dysfunction
      and pulmonary hypertension in pediatric acute respiratory distress syndrome are
      unknown. We aimed to describe the prevalence of right ventricular dysfunction and
      pulmonary hypertension within 24 hours of pediatric acute respiratory distress
      syndrome diagnosis and their associations with outcomes. DESIGN: Retrospective,
      single-center cohort study. SETTING: Tertiary care, university-affiliated PICU.
      PATIENTS: Children who had echocardiograms performed within 24 hours of pediatric
      acute respiratory distress syndrome diagnosis. INTERVENTIONS: None. MEASUREMENTS
      AND MAIN RESULTS: Between July 1, 2012, and June 30, 2016, 103 children met
      inclusion criteria. Echocardiograms were analyzed using established indices of
      right ventricular and left ventricular systolic function and for evidence of
      pulmonary hypertension. Echocardiographic abnormalities were common: 26% had low
      right ventricular fractional area change, 65% had low tricuspid annular plane
      systolic excursion, 30% had low left ventricular fractional shortening, and 21%
      had evidence of pulmonary hypertension. Abnormal right ventricular global
      longitudinal strain and abnormal right ventricular free wall strain were present
      in 35% and 40% of patients, respectively. No echocardiographic variables differed
      between or across pediatric acute respiratory distress syndrome severity. In
      multivariable analyses, right ventricular global longitudinal strain was
      independently associated with PICU mortality (odds ratio, 3.57 [1.33-9.60]; p =
      0.01), whereas right ventricular global longitudinal strain, right ventricular
      free wall strain, and the presence of pulmonary hypertension were independently
      associated with lower probability of extubation (subdistribution hazard ratio,
      0.46 [0.26-0.83], p = 0.01; subdistribution hazard ratio, 0.58 [0.35-0.98], p =
      0.04; and subdistribution hazard ratio, 0.49 [0.26-0.92], p = 0.03,
      respectively). CONCLUSIONS: Early ventricular dysfunction and pulmonary
      hypertension were detectable, prevalent, and independent of lung injury severity
      in children with pediatric acute respiratory distress syndrome. Right ventricular
      dysfunction was associated with PICU mortality, whereas right ventricular
      dysfunction and pulmonary hypertension were associated with lower probability of
      extubation.

PMID- 30095505
TI  - Parents' Awareness and Perceptions of Sport Specialization and Injury Prevention
      Recommendations.
AB  - OBJECTIVE: To conduct a survey of parents to determine their knowledge of sport
      volume recommendations and examine their perceptions toward sport specialization.
      DESIGN: Cross-sectional survey. SETTING: Youth sport athletic tournaments,
      competitions, and practices. PATIENTS OR OTHER PARTICIPANTS: Parents (n = 1000,
      614 women, age: 44.5 +/- 6.7 years) of youth athletes completed the survey.
      Parents had to have a child between 10 and 18 years of age who participated in
      organized sport in the previous 12 months. INTERVENTIONS: The survey was
      anonymous and consisted of yes/no and Likert-scale questions and consisted of
      background of parent and child and perceptions and knowledge of safe sport
      recommendations. An expert panel validated the survey. MAIN OUTCOME MEASURES:
      Data were summarized by frequencies, proportions (%), and mean values and SDs,
      when appropriate. Chi-square analyses were used to determine if parent sex
      influenced distributions. RESULTS: Over 80% of parents had no knowledge of sport
      volume recommendations regarding h/wk (84.5%), mo/yr (82.2%), or simultaneous
      participation in multiple leagues (89.9%). Twenty-four percent of parents
      considered it appropriate to participate in multiple leagues in the same sport,
      whereas 60.5% considered it appropriate to participate in multiple leagues of a
      different sport. Thirty-four percent of parents indicated that they were
      concerned about the risk of injury in youth sports. Although 55% of parents
      considered sport specialization a problem in youth sports, only 43.3% thought
      that year-round sport participation increased the chances of sustaining an
      overuse injury. Female parents were more likely to be concerned about injury and
      believe that year-round sport participation results in overuse injury compared
      with men. CONCLUSIONS: Recommendations associated with youth sport participation
      are not well known. However, parents are concerned about the risk of injury and
      consider sport specialization a problem.

PMID- 30095504
TI  - Immediate and Short-Term Effects of Short- and Long-Duration Isometric
      Contractions in Patellar Tendinopathy.
AB  - OBJECTIVES: Isometric muscle contractions are used in the management of patellar
      tendinopathy to manage pain and improve function. Little is known about whether
      long- or short-duration contractions are optimal to improve pain. This study
      examined the immediate and short-term (4 weeks) effects of long- and short
      duration isometric contraction on patellar tendon pain, and tendon adaptation.
      DESIGN: Repeated measures within groups. SETTING: Clinical primary care.
      PATIENTS: Participants (n = 16, males) with patellar tendinopathy. INTERVENTION:
      Short-duration (24 sets of 10 seconds) or long-duration (6 sets of 40 seconds)
      isometric knee extension loading (85% maximal voluntary contraction), for 4
      weeks. MAIN OUTCOME MEASURE: Immediate change in pain with single-leg decline
      squat (SLDS) and hop, as well as change in pain and tendon adaptation [within
      session anterior-posterior (AP) strain] were assessed over 4 weeks. RESULTS: Pain
      was significantly reduced after isometric loading on both SLDS (P < 0.01) and hop
      tests (P < 0.01). Pain and quadriceps function improved over the 4 weeks (P <
      0.05). There was significant AP strain at each measurement occasion (P < 0.01).
      Although transverse strain increased across the training period from ~14% to 22%,
      this was not significant (P = 0.08). CONCLUSIONS: This is the first study to show
      that short-duration isometric contractions are as effective as longer duration
      contractions for relieving patellar tendon pain when total time under tension is
      equalized. This finding provides clinicians with greater options in prescription
      of isometric loading and may be particularly useful among patients who do not
      tolerate longer duration contractions. The trend for tendon adaptation over the
      short 4-week study period warrants further investigation.

PMID- 30095506
TI  - Can Ultrasound Identify Paradoxical Vocal Fold Movement? A Pilot Study.
AB  - OBJECTIVE: Vocal cord dysfunction (VCD) is characterized by paradoxical vocal
      fold movement (PVFM) during inspiration. The aim of this study was to determine
      whether ultrasound could accurately differentiate between normal and PVFM during
      respirations in a resting state. DESIGN: Prospective, single-subject design.
      SETTING: Academic medical center. PATIENTS: A speech-language pathologist who was
      able to volitionally alternate between normal and PVFM when breathing at rest was
      recruited to participate in the study. INTERVENTIONS: The subject was instructed
      to randomly alternate between normal and PVFM 20 times (10 times each). A single
      investigator imaged the vocal folds using ultrasound and reported when the
      subject alternated between the 2 respiratory states. MAIN OUTCOME MEASURES: The
      subject recorded when they changed between the 2 respiratory states, whether the
      investigator identified with the change occurred, and if the correct respiratory
      state was identified. RESULTS: The investigator recognized when the subject
      changed respiratory states and correctly identified the new respiratory state
      100% of the time. CONCLUSIONS: The findings of the current study were promising
      and suggest that ultrasound may have utility in the diagnosis of VCD. However,
      because of the preliminary nature of these results, further research is required
      before recommending its clinical implementation.

PMID- 30095507
TI  - Effectiveness of an Exercise-Based Active Rehabilitation Intervention for Youth
      Who Are Slow to Recover After Concussion.
AB  - OBJECTIVE: (1) To determine the impact of providing participants aged 8 to 17
      years who are slow to recover after a concussion with a well-developed active
      rehabilitation intervention (ARI), compared with receiving standard care alone,
      on postconcussion symptoms (PCS) at 2 and 6 weeks after the initiation of ARI;
      and (2) to investigate functional recovery 6 weeks after initiation of ARI.
      DESIGN: A multicenter prospective quasi-experimental control group design.
      SETTING: Tertiary care pediatric trauma center and community health care
      providers. PARTICIPANTS: Forty-nine youth were enrolled (experimental n = 36;
      control n = 13). PROCEDURES: Participants were assessed on 3 different occasions:
      (1) initial visit (baseline); (2) 2 weeks; and (3) 6 weeks after enrollment. MAIN
      OUTCOME MEASURES: Child- and parent-reported PCS were obtained by the PCS
      Inventory Scale (primary outcome). Secondary outcomes included: (1) mood and
      anxiety; (2) quality of life; (3) energy level; (4) coordination and balance; (5)
      neurocognition; (6) parental anxiety; and (7) satisfaction with intervention.
      RESULTS: Both groups reported decrease of PCS over time (child: P = 0.01; parent:
      P = 0.03). Children in the experimental group presented higher quality of life (P
      = 0.04) and less anger (P = 0.02). A trend toward significance was observed for
      better tandem gait (P = 0.07) and for less general fatigue on self-reported PCS
      (P = 0.09) in the experimental group. CONCLUSIONS: Active rehabilitation
      intervention does not affect the PCS beyond the usual management, but it
      increases their quality of life, decreases anger, and potentially increases
      energy level and balance.

PMID- 30095495
TI  - The Association of Nutrition Status Expressed as Body Mass Index z Score With
      Outcomes in Children With Severe Sepsis: A Secondary Analysis From the Sepsis
      Prevalence, Outcomes, and Therapies (SPROUT) Study.
AB  - OBJECTIVES: The impact of nutrition status on outcomes in pediatric severe sepsis
      is unclear. We studied the association of nutrition status (expressed as body
      mass index z score) with outcomes in pediatric severe sepsis. DESIGN: Secondary
      analysis of the Sepsis Prevalence, Outcomes, and Therapies study. Patient
      characteristics, ICU interventions, and outcomes were compared across nutrition
      status categories (expressed as age- and sex-adjusted body mass index z scores
      using World Health Organization standards). Multivariable regression models were
      developed to determine adjusted differences in all-cause ICU mortality and ICU
      length of stay by nutrition status. SETTING: One-hundred twenty-eight PICUs
      across 26 countries. PATIENTS: Children less than 18 years with severe sepsis
      enrolled in the Sepsis Prevalence, Outcomes, and Therapies study (n = 567).
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Nutrition status data were
      available for 417 patients. Severe undernutrition was seen in Europe (25%), Asia
      (20%), South Africa (17%), and South America (10%), with severe overnutrition
      seen in Australia/New Zealand (17%) and North America (14%). Severe
      undernutrition was independently associated with all-cause ICU mortality
      (adjusted odds ratio, 3.0; 95% CI, 1.2-7.7; p = 0.02), whereas severe
      overnutrition in survivors was independently associated with longer ICU length of
      stay (1.6 d; p = 0.01). CONCLUSIONS: There is considerable variation in nutrition
      status for children with severe sepsis treated across this selected network of
      PICUs from different geographic regions. Severe undernutrition was independently
      associated with higher all-cause ICU mortality in children with severe sepsis.
      Severe overnutrition was independently associated with greater ICU length of stay
      in childhood survivors of severe sepsis.

PMID- 30095508
TI  - Female Sport Participation Effect on Long-Term Health-Related Quality of Life.
AB  - BACKGROUND: Female participation in sport has grown substantially over the last 4
      decades. OBJECTIVES: We investigated the association between sports participation
      and (1) later-life health outcomes and (2) later-life quality-of-life (QoL)
      measures among female college alumni. METHODS: We conducted a cross-sectional
      study of female alumni between the ages of 40 and 70 years. Participants
      completed a questionnaire that included QoL measures assessing general health,
      negative consequences of alcohol use, mental health, and other self-reported
      health outcomes. We divided alumni into athletes and nonathletes. Between-group
      comparisons of health outcomes were adjusted for age; QoL measures were adjusted
      for age, exercise habits, cigarette smoking, alcohol use, and comorbidities.
      RESULTS: Questionnaires were sent to 47 836 alumni, 3702 (8%) responded. Forty
      four percent of female respondents participated in collegiate sports. After
      adjusting for age, female respondents who participated in collegiate sports were
      more likely to exercise >3*/week (61.8% vs 50.2%; P <= 0.001), view themselves in
      good/great health (91% vs 85%; P < 0.001), and less likely to have ever smoked
      (13.6% vs 25.3%; P <= 0.001) or used recreational drugs (7.5% vs 9.5%; P =
      0.018). A smaller proportion of female athletes reported hypertension (5.5% vs
      13.5%; P <= 0.001), high cholesterol (9.9% vs 17.0%; P < 0.001), and obesity
      (3.1% vs 6.8%; P = 0.001) compared with nonathletes. Participation in sports was,
      however, associated with decreased mobility (R = 0.1826; P = 0.002) and increased
      anxiety (R = 0.039; P = 0.016) QoL scores. CONCLUSIONS: Sports participation for
      female collegiate athletes was associated with mostly positive health outcomes,
      but also with lower mobility and increased anxiety QoL scores.

PMID- 30095509
TI  - Using Continuous Vital Sign Monitoring to Detect Early Deterioration in Adult
      Postoperative Inpatients.
AB  - BACKGROUND: Episodic vital sign collection (eVSC), as single data points, gives
      an incomplete picture of adult patients' postoperative physiologic status. LOCAL
      PROBLEM: Late detection of patient deterioration resulted in poor patient
      outcomes on a postsurgical unit. METHODS: Baseline demographic and outcome data
      were collected through retrospective chart review of all patients admitted to the
      surgical unit for 12 weeks prior to this quality improvement project. Data on the
      same outcomes were collected during the 12-week project. INTERVENTION: This
      project compared outcomes between the current standard of eVSC and the proposed
      standard of continuous vital sign monitoring (cVSM). RESULTS: Using cVSM
      demonstrated a statistically significant 27% decrease in the complication rate,
      and a clinically significant decrease in transfers to an intensive care unit and
      failure-to-rescue (FTR) events rate. CONCLUSIONS: cVSM demonstrated detection of
      early signs of patient deterioration to prevent FTR.

PMID- 30095510
TI  - Is telemedicine your cup of tea?

PMID- 30095511
TI  - Amyotrophic lateral sclerosis: A guide to collaborative care.
AB  - With the incidence of amyotrophic lateral sclerosis (ALS) increasing over recent
      decades, wide variability in disease presentation, and a median survival of only
      2 to 4 years from disease onset, timely referral is key for patients with
      suspected ALS. This article discusses primary care providers' roles in
      recognizing ALS and managing symptoms in patients whose travel to specialists can
      become restricted in the later stages of the disease.

PMID- 30095512
TI  - Recommendations for evaluating and managing idiopathic pulmonary fibrosis.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by
      progressive and irreversible fibrosis of lung parenchyma that reduces lung
      function. This rare, incurable disease often is mistaken for an inflammatory
      condition. IPF typically manifests in older men and is associated with a history
      of smoking. Disease progression is rapid, with a 5-year survival rate of 20%.
      Treatment options include lung transplantation and medical therapies to reduce
      the steady decline in lung function. This article reviews the epidemiology,
      pathophysiology, presentation, diagnosis, and management of IPF.

PMID- 30095513
TI  - Comprehensive Review of the Elbow Physical Examination.
AB  - Physical examination of the elbow is a critical component in formulating an
      accurate diagnosis. Various special physical examinations have been described to
      improve the clinician's ability to establish an accurate diagnosis. A
      comprehensive approach to the physical examination of the elbow, including
      special tests, may facilitate improved diagnosis of elbow pathology.

PMID- 30095514
TI  - Glenohumeral Osteoarthritis in the Young Patient.
AB  - Glenohumeral osteoarthritis in the young patient (aged <60 years) is a difficult
      condition, given both age and functional demands. Primary osteoarthritis is the
      most common etiology in this patient demographic, but secondary causes include
      osteonecrosis, previous trauma (eg, fracture-dislocation), previous infection
      (eg, septic arthritis), previous capsulorrhaphy, previous arthroscopic surgery
      (eg, chondrolysis), and glenoid dysplasia. Nonsurgical modalities, including
      activity modification, pharmacotherapy, physical therapy, and intra-articular
      injections, are the mainstay of management; however, in young patients who have
      exhausted nonsurgical management, surgical options include arthroscopic
      debridement, humeral head replacement with or without glenoid treatment (ie,
      biologic glenoid resurfacing, glenoid reaming), and total or reverse total
      shoulder arthroplasty. Unfortunately, failure rates after surgical management are
      considerably higher in young patients compared with those observed in older, more
      sedentary patients. Here, we focus on the etiology, evaluation, and management of
      young patients with glenohumeral osteoarthritis, with a focus on clinical
      outcomes.

PMID- 30095515
TI  - Use of Intrawound Antibiotics in Orthopaedic Surgery.
AB  - Intrawound antibiotics have been used in orthopaedic surgery procedures to
      prevent the development of surgical site infections. Local delivery of antibiotic
      powder has demonstrated a notable reduction in surgical site infection in rabbit
      and rodent in vivo models, as well as in other surgical fields, including
      vascular, colorectal, cardiothoracic, and dermatologic surgery. Intrawound
      antibiotic powder has been used in many orthopaedic applications, including spine
      surgery, total joint arthroplasty, trauma, foot and ankle reconstruction, and
      elbow surgery. Although the theory behind the use of intrawound antibiotic powder
      is promising, it has potential adverse effects, including antibiotic resistance,
      circulatory collapse, and decreased bone healing. In addition, most studies in
      the orthopaedic literature on the use of intrawound antibiotic powder are
      retrospective in nature.

PMID- 30095516
TI  - Knee Pain After Intramedullary Nailing of Tibia Fractures: Prevalence, Etiology,
      and Treatment.
AB  - Intramedullary nailing is often the treatment of choice for fractures of the
      tibia, but postoperative knee pain is common after this procedure. Potential
      etiologies include implant prominence, injury to intra-articular structures,
      patellar tendon or fat pad injury, damage to the infrapatellar branch of the
      saphenous nerve, and altered biomechanics. Depending on the etiology, described
      treatment options include observation, implant removal, assessment and treatment
      of injured intra-articular structures, and selective denervation. Careful
      attention to appropriate starting point and implant selection combined with more
      recently described semiextended nailing techniques may aid in prevention of knee
      pain.

PMID- 30095517
TI  - NACNS Newsletter: President's Message.

PMID- 30095518
TI  - Improving Outcomes Reporting.

PMID- 30095519
TI  - Does the Future Hold Promise for Online Bioethicist Consultations?

PMID- 30095520
TI  - Avoid Common Mistakes When Presenting Your Research, Evidence-Based Practice, or
      Quality Improvement Projects.

PMID- 30095521
TI  - Think Kratom Is a Safe Opioid Substitute? Think Again!: History, Evidence, and
      Possible Future for Mitragyna speciosa.

PMID- 30095522
TI  - Characteristics of Adults Managing Vitamins/Supplements and Prescribed
      Medications-Who Is Using, Not Using, and Abandoning Use of Pillboxes?: A
      Descriptive Study.
AB  - PURPOSE: Evidence suggests pillboxes are effective for improving medication
      adherence. However, prior descriptive studies about pillbox use are limited to
      studies of older adults or condition-specific studies. This study describes
      characteristics of adults with chronic conditions and their use of pillboxes.
      METHODS: A survey questionnaire link was posted on a social media recruitment
      page from August 2016 to April 2017. RESULTS: The sample of 179 people was middle
      age (47.7 +/- 15.4 years), predominantly white (90.4%), educated (>93% educated
      beyond high school), female (n = 148; men n = 26), married/partner (58.2%), and
      working full time (55.9%). Pillboxes were used by 66% (n = 118) of the sample at
      some point; 22.9% reported pillbox abandonment. Compared with people who never
      used a pillbox, current pillbox users were older (53.2 +/- 14.3 vs 42.0 +/- 14.4
      years; P < .001) and took more vitamins/supplements (3.9 +/- 3.8 vs 2 +/- 1.8, P
      = .002) and prescribed medications (4.2 +/- 2.2 vs 2.6 +/- 1.9, P < .001).
      Adherence did not differ between groups; pillbox users were more likely to refill
      medications before running out compared with those abandoning use, P < .001.
      CONCLUSION: Age and number of medications may affect pillbox use. Future research
      should explore barriers to continued use of pillboxes and uptake in younger
      populations.

PMID- 30095523
TI  - Irish Respiratory Clinical Nurse Specialists' Experiences of Their Role: A
      Qualitative Exploration.
AB  - AIM AND OBJECTIVES: The aim of this study was to explore respiratory clinical
      nurse specialists' (CNSs') experiences of their role. BACKGROUND: Respiratory
      illnesses are currently 1 of the top 3 causes of mortality resulting in 1 in 5
      deaths and are associated with significant human burden. Respiratory CNSs play a
      vital role in the management of respiratory disease through supporting
      improvements in quality of life, reduction of exacerbations, and subsequent
      hospital admission. While published literature exists regarding the CNS role,
      there is a dearth of published literature on the respiratory CNS role. DESIGN: A
      qualitative descriptive design allowed the researcher to elicit respiratory CNSs'
      experiences of their role. METHODS: Ethical approval was obtained, CNSs were
      purposively sampled (n = 10), and data were collected by semistructured
      interviews, transcribed, and analyzed using content thematic analysis. RESULTS:
      Three themes were identified within the findings: "multidimensional role,"
      "interacting and collaborating," and "advancing the role." CONCLUSIONS: Overall
      the study highlights that respiratory CNSs are active in the role as clinical
      experts, advocators, educators, collaborators, consultants, and health promoters.
      These findings recognize the importance of evaluating and building on the current
      CNS workforce in respiratory care and evaluating future development of the CNS
      role in specialized aspects of respiratory care in line with population and
      service needs.

PMID- 30095524
TI  - Use of a Systematic Consultation Process to Facilitate Nursing Research Projects:
      An Exemplar.
AB  - PURPOSE/OBJECTIVES: The purpose of this article is to describe the use of a well
      established, 5-stage consultation process, to advise a research team on planning
      strategies to engage domestic violence shelters (DVSs) as community partners in
      their study. The research team is testing a health promotion intervention for
      teens living in shelters with their parent and needed to enlist shelters as sites
      to recruit teens and conduct the intervention. Consultation aims were to (a)
      identify highly promising strategies described in peer-reviewed literature for
      identifying, recruiting, and collaborating with community organizations in
      research and (b) identify DVSs that would potentially serve as effective
      community partners for the study. METHODS: A clinical nurse specialist and a
      public health master's degree student led the consultation. The consultation
      process included (a) a systematic review of 29 peer-reviewed articles about
      research or program evaluation studies that engaged community partners and (b) a
      comprehensive online search of information about DVSs. OUTCOMES: Consultants
      identified 104 strategies used in studies to engage community partners and 10
      specific DVSs most likely to effectively engage in the study. CONCLUSION:
      Clinical nurse specialists are well situated to provide consultation to research
      teams and should follow well-established consultation processes and systematic
      data collection procedures.

PMID- 30095525
TI  - A Qualitative Study of Specialized Clinical Nurses' Perceptions of Good Care in
      Practice.
AB  - PURPOSE/AIMS: The aim of this study was to explore specialized clinical nurses'
      (SCNs') perceptions of "good care" through descriptions of actual care
      experiences. DESIGN: We used a qualitative design with a conventional content
      analysis approach. METHODS: We conducted semistructured interviews with 24 SCNs.
      These nurses have passed specialized clinical courses, are master's or bachelor's
      degree prepared, have additional course work beyond the bachelor degree, and
      practice with an expanded scope of responsibility. The participants were
      purposively sampled from general and specialty hospitals, and 6 field notes were
      collected. RESULTS: We identified 3 overarching themes to classify the findings:
      patient-centered care, knowledge-based care, and skillful practice. Participants
      regarded these 3 components as interdependent and related, which we conceptualize
      as 3 sides of an equilateral triangle termed the Good Care Triangle. CONCLUSIONS:
      The Good Care Triangle provides a heuristic approach to consider professional
      standards from the perspectives of SCNs and provides needed insight into SCNs'
      perspectives on the fundamental yet underexplored concept of good care. Clinical
      leaders can consider how the 3 themes identified are reflected and enacted in the
      care practices of SCNs. Future research could examine the utility of the Good
      Care Triangle in guiding nursing education and evaluating SCNs' perspectives of
      the care that they are providing.

PMID- 30095526
TI  - Taking Lemons and Making Lemonade: Posttraumatic Growth From Pediatric Cancer.
AB  - PURPOSE: The purpose of this study was to examine the lived experiences of the
      perceived long-term effects of pediatric cancer on adult survivors and whether
      these effects had bearing on their primary support persons. DESIGN: This work was
      guided by van Manen's "new" interpretive phenomenology. METHODS: Ten survivors of
      pediatric cancer (aged 21-28 years) and 9 of their support persons (aged 23-73
      years) were recruited. Background questionnaires were administered, and
      interviews were conducted. Field notes were collected, and member checks were
      administered for data credibility. RESULTS: A total of 4 themes emerged from this
      work; however, only the theme discussing posttraumatic growth will be discussed.
      Posttraumatic growth manifested in different ways, such as motivation for career
      or schooling choices, doing charity work, working with cancer organizations, or
      mentoring children undergoing pediatric cancer treatment. CONCLUSIONS: This work
      may provide comfort to other individuals with pediatric cancer knowing that they
      are not alone in their journeys. Healthcare providers should attempt to make
      pediatric cancer experiences as "normal" as possible for patients and their
      families and observe for signs of stress in their patients. As well, it is
      important for the pediatric cancer literature to illustrate that young adult
      survivors of pediatric cancer find positive outcomes in their experiences.

PMID- 30095528
TI  - Think Kratom Is a Safe Opioid Substitute? Think Again!: History, Evidence, and
      Possible Future for Mitragyna speciosa.

PMID- 30095529
TI  - Age-Related Variations in Corneal Asphericity and Long-Term Changes.
AB  - PURPOSE: Corneal front-surface asphericity is directly related with the optical
      quality of the eye and with contact lenses fitting. The purpose of this study was
      to evaluate the corneal asphericity as a function of age, sex, and refractive
      error measured with autokeratometry and corneal topography and its long-term
      changes (5- to 10-year period). METHODS: The asphericity and corneal curvature
      were obtained with the autorefractometer/autokeratometer NIDEK ARK-700A and with
      the videokeratoscope MODI 2.0 and compared. Corneal asphericity was
      retrospectively analyzed with NIDEK ARK-700A. The longitudinal study of
      asphericity was conducted with the same device between 2 appointments within an
      interval of 5 to 10 years. RESULTS: NIDEK ARK-700A showed agreement of
      asphericity values with those of MODI 2.0 (P=0.172) for a 7-mm diameter chord.
      The mean Q value of 1,484 right eyes (58.6% female), with a mean age of 40.2+/
      18.4 years, was -0.24+/-0.12. No differences were found for Q value between sexes
      (P=0.424), age groups (P=0.268), and refractive error groups (P=0.107). The
      longitudinal analysis of corneal asphericity in 190 eyes (62.1% female) over a
      mean period of 5.9+/-1.4 years showed no significant differences in the Q value
      (0.00+/-0.08, P=0.813) over time. However, 14% showed asphericity changes of +/
      0.10 or higher while 86% of the subjects showed a change below +/-0.10.
      CONCLUSIONS: The mean Q value observed in this study agrees with the average
      values of a white population and contributes to slightly reduce the positive
      spherical aberration of the eye. For the large majority of this population, the
      asphericity did not show significant changes within a period of 5 to 10 years,
      but significant changes can be observed in some patients.

PMID- 30095527
TI  - Art, Body, and Soul: A Conversation With Nawal Nasrallah.

PMID- 30095530
TI  - Corneal Sensitivity After Ocular Surgery.
AB  - The cornea is densely innervated with free nerve endings to provide a high level
      of sensitivity to foreign bodies or noxious substances. They also provide trophic
      support to the tissues of the cornea and facilitate their repair and replacement.
      Any reduction in the function of the nerve endings through disease, contact lens
      wear, or surgery may lead to corneal disease, damage, or reduced healing.
      Assessment of the corneal nerve function can be made by the use of specialized
      instruments (aesthesiometers) that stimulate the corneal nerves using different
      modalities-mechanical, chemical, and thermal. Each modality assesses the function
      of a different cohort of corneal nerve type. Ocular surgery, particularly corneal
      surgery, can produce significant damage to the corneal innervation. However, for
      the majority of surgical procedures, corneal sensation eventually returns to
      preoperative levels, given enough time. The principal exceptions to this are
      penetrating keratoplasty, epikeratophakia, and cryo-keratomileusis, where
      sensation rarely returns to normal. For all types of surgery, the pattern of
      corneal sensation loss and recovery depends on the type, depth, and extent of
      incision because these influence the number of nerve fibers severed, and on the
      healing response of the patient.

PMID- 30095531
TI  - Successfully Improving Visual Acuity in Keratitis-Ichthyosis-Deafness Syndrome
      Utilizing Gas-Permeable Lenses: A Case Report.
AB  - There is currently no well-defined guideline for treatment and management of
      patients with keratitis-ichthyosis-deafness (KID) syndrome, and most patients
      will face disabling vision loss due to corneal neovascularization and
      cicatrization. We offer this case as an example of how we can improve visual
      acuity (VA) and quality of life even in advanced cases of corneal
      neovascularization. We showcase the use of gas-permeable (GP) contact lenses to
      provide useful, functional VA in a patient with long-standing visual impairment
      secondary to corneal neovascularization and irregularity due to KID syndrome. The
      patient's VA improved from 20/200 both eyes (OU) to 20/40 OU with successful
      fitting of GP lenses, which additionally relieved the patient's otherwise
      intractable monocular diplopia.

PMID- 30095532
TI  - Identifying the Employment Needs of People With Chronic Health Conditions in
      Europe.
AB  - OBJECTIVES: The main goal of this study was to compare the employment needs
      experienced by people with different chronic health conditions and in different
      welfare systems. METHODS: A total of 688 participants with six chronic health
      conditions were collected in nine countries representing four welfare systems in
      Europe (Continental, Mediterranean, Postcommunist, and Scandinavian). RESULTS:
      Raising awareness of what is to live with a chronic health condition in the
      workplace was the area perceived as more favorable. The types of employment needs
      were different across the social welfare systems but did not vary among the
      different chronic health conditions groups. CONCLUSION: Although diverse, there
      appear to be some common needs transversal to the working experience of people
      with chronic health problems. Actions to improve the employability of people with
      chronic health conditions should be tailored to each welfare system.

PMID- 30095533
TI  - Practices and Attitudes of Michigan-Based Occupational Physicians Regarding Adult
      Immunization.
AB  - OBJECTIVE: To assess practices and barriers regarding adult immunizations, among
      occupational and environmental physicians in Michigan. METHODS: A 10-item
      multiple choice web based questionnaire was designed after reviewing the Centers
      for Disease Control and Prevention recommendations and the current literature on
      adult immunization standards. RESULTS: Assessing immunization status is common
      practice for 62% of respondents. 92% of respondents recommend the annual
      influenza vaccination, unless contraindicated. The most commonly reported
      barriers included the cost of providing immunizations and the prioritization of
      acute over preventative care. Use of standing order vaccinations and reminder
      recall systems were popular strategies used to improve vaccination rates.
      CONCLUSIONS: Occupational physicians frequently recommend influenza, tetanus, and
      hepatitis B vaccines when indicated, but are less likely to order other vaccines
      for patients. Promotion of a more comprehensive assessment of immunity needs in
      the workplace may improve national vaccine coverage.

PMID- 30095536
TI  - Initial Impairment and Recovery of Vision-Related Functioning in Participants
      With Acute Optic Neuritis From the RENEW Trial of Opicinumab.
AB  - BACKGROUND: Leucine-rich repeat and immunoglobulin domain-containing Nogo
      receptor-interacting protein 1(LINGO-1 is a key suppressor of oligodendrocyte
      differentiation and axonal remyelination and regeneration. This analysis
      evaluated the potential benefit of opicinumab, a human monoclonal antibody
      against LINGO-1, vs placebo on exploratory clinical endpoints of patient-reported
      vision-related functioning and high-contrast visual acuity (HCVA) in RENEW
      participants with acute optic neuritis (AON). METHODS: Participants were
      randomized to 100 mg/kg opicinumab intravenous or placebo every 4 weeks (6
      infusions). Assessments were conducted in the per-protocol (PP) population and
      included: 25-item National Eye Institute Visual Functioning Questionnaire (NEI
      VFQ-25), 10-item Neuro-Ophthalmic Supplement (NOS-10), and HCVA. RESULTS: The
      opicinumab group (n = 33) had worse mean (SD) baseline patient-reported vision
      related functioning scores vs placebo (n = 36): NEI-VFQ-25 composite, 75.5 (17.6)
      vs 79.0 (16.6); NOS-10 composite, 63.6 (19.8) vs 69.8 (21.2), respectively. By
      Week 24, the placebo and opicinumab groups experienced substantial mean
      improvements from baseline (NEI-VFQ-25 composite, 15.17 vs 13.51 [difference (95%
      CI): -1.66 (-5.11 to 1.78)]; NOS-10 composite, 17.40 vs 16.04 [difference (95%
      CI): -1.35 (-7.38 to 4.67)]). Between-treatment differences in mean change from
      baseline were not significantly different at any time point. Analysis of
      covariance-adjusted mean recovery from baseline in HCVA at Week 24 for the
      affected eyes was 11.8 and 8.7 letters for placebo and opicinumab, respectively
      (P = 0.202). CONCLUSIONS: Most participants in the RENEW PP population
      demonstrated substantial recovery from baseline in patient-reported vision
      related functioning and HCVA, regardless of treatment and structural damage.
      Average scores after recovery remained lower than those of published disease-free
      control groups. These results provide important information on visual function
      recovery in patients with AON, as measured by NEI-VFQ-25 and NOS-10.This is an
      open-access article distributed under the terms of the Creative Commons
      Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is
      permissible to download and share the work provided it is properly cited. The
      work cannot be changed in any way or used commercially without permission from
      the journal.

PMID- 30095534
TI  - Protocol for process evaluation of evidence-based care pathways: the case of
      colorectal cancer surgery.
AB  - BACKGROUND AND AIM: Care pathways are complex interventions, consisting of
      multiple 'active ingredients', to structure care processes around patient needs.
      Numerous studies have reported improved outcomes after implementation of care
      pathways. The structure-process-outcome framework and the context-mechanism
      outcome framework both suggest that outcomes can only be achieved through a
      certain process within a context or structure. To understand how and why care
      pathways are effective, understanding of both this process and context is
      necessary. The aim of this article is to propose a study protocol to evaluate the
      implementation process of evidence-based care pathways, including the influence
      of the context. This protocol is explained by applying it to the implementation
      of a colorectal cancer surgery pathway in an international setting. METHODS: The
      Medical Research Council (MRC) guidance on process evaluations for complex
      interventions is used as the basis for the protocol. The key components of
      process evaluation are intervention, context, implementation, mechanisms of
      impact and outcomes. In process evaluations, these components are studied using
      quantitative and qualitative methods. Among them are patient record analysis,
      questionnaires, on-site visits and interviews. DISCUSSION: To guide our
      methodological choices, the MRC guidance for process evaluations of complex
      interventions, and published protocols for process evaluations of complex
      interventions were used. Our protocol is now tailored for the process evaluation
      of evidence-based care pathways and provides researchers and clinicians methods
      and tools, as well as a worked example, that can be used to study the process of
      care pathway implementation. As a result, healthcare professionals will be
      informed on context factors and implementation processes that can facilitate the
      implementation of care pathways, improving quality and effectiveness of care
      processes.

PMID- 30095537
TI  - Visual Snow: Visual Misperception.
AB  - BACKGROUND: Visual snow (VS) is a constant visual disturbance described as
      flickering dots occupying the entire visual field. Recently, it was characterized
      as the defining feature of a VS syndrome (VSS), which includes palinopsia,
      photophobia, photopsias, entoptic phenomena, nyctalopia, and tinnitus. Sixty
      percent of patients with VSS also experience migraine, with or without aura. This
      entity often is considered psychogenic in nature, to the detriment of the
      patient's best interests, but the high frequency of similar visual symptoms
      argues for an organic deficit. The purpose of this review is to clarify VSS as a
      true entity and elaborate the nature of individual symptoms and their
      relationship to each other. EVIDENCE ACQUISITION: The literature was reviewed
      with specific regard to the clinical presentation and psychophysical,
      neurophysiological, and functional imaging studies in patients with defined
      visual disturbances that comprise VSS. RESULTS: Consideration of the individual
      symptoms suggests that multiple factors are potentially involved in the
      development of VSS, including subcortical network malfunction and cortical
      hyperexcitation. Although there is substantial overlap between VSS and migraine
      syndromes in terms of co-occurring symptoms, both neurophysiological and
      neuroimaging studies provide substantial evidence of separate abnormalities of
      processing, supporting these as separate syndromes. CONCLUSIONS: VSS is likely
      associated with either hyperactive visual cortices or, alternatively, impaired
      processing of simultaneous afferent information projecting to cortex. VSS likely
      results from widespread disturbance of sensory processing resulting in sensory
      misperception. There may be a number of syndromes associated with impaired
      sensory processing resulting in sensory misperception, including migraine,
      persistent perceptual postural dizziness, and tinnitus, which overlap with VSS.
      Elucidation of abnormality in one defined syndrome may provide a path forward for
      investigating all.

PMID- 30095538
TI  - Implementing a Warm Handoff Between Hospital and Skilled Nursing Facility
      Clinicians.
AB  - OBJECTIVES: Care transitions between hospitals and skilled nursing facilities
      (SNFs) are associated with disruptions in patient care and high risk for adverse
      events. Communication between hospital-based and SNF-based clinicians is often
      suboptimal; there have been calls to foster direct, real-time communication
      between sending and receiving clinicians to enhance patient safety. This article
      described the implementation of a warm handoff between hospital and SNF
      physicians and advanced practice providers at the time of hospital discharge.
      METHODS: Before patient transfer, hospital clinicians called SNF clinicians to
      provide information relevant to the continuation of safe patient care and offer
      SNF clinicians the opportunity to ask clarifying questions. The calls were
      documented in the hospital discharge summary. RESULTS: A total of 2417 patient
      discharges were eligible for inclusion. Warm handoffs were documented at an
      increasing rate throughout implementation of the intervention, beginning with
      15.78% (n = 3) in stage 1, then 20.27% (n = 75) in stage 2, and finally 46.89% (n
      = 951) in stage 3. The overall average rate of documentation was 42.57%.
      Participant feedback indicated that clinicians were most concerned about
      understanding the purpose of the warm handoff, managing their workload, and
      improving the efficiency of the process. CONCLUSIONS: Use of a warm handoff
      showed promise in improving communication during hospital-SNF patient transfers.
      However, the implementation also highlighted specific barriers to the handoff
      related to organizational structures and clinician workload. Addressing these
      underlying issues will be critical in ensuring continued participation and
      support for efforts that foster direct communication among clinicians from
      different healthcare institutions.

PMID- 30095540
TI  - The Stromal Vascular Fraction Improves Maintenance of the Fat Graft Volume: A
      Systematic Review.
AB  - BACKGROUND AND OBJECTIVES: With the continued application of fat grafting in
      plastic surgery, many studies have focused on various factors to improve
      maintenance of the fat graft volume, such as platelet-rich plasma, adipose
      derived stromal/stem cells, and the stromal vascular fraction (SVF). In addition,
      many review articles have investigated the functions of platelet-rich plasma and
      adipose-derived stromal/stem cells in fat grafting, although the usefulness of
      the SVF remains unclear. The aim of the present review was to determine whether
      SVF use could maintain a fat graft. METHODS: A systematic review was conducted of
      the PubMed, Cochrane Central Register of Controlled Trials, and Embase databases
      of original articles published up to February 2018. RESULTS: Relevant articles
      were identified by screening the abstracts. A total of 58 full texts were
      initially identified. After exclusion, 17 articles, including 6 animal studies
      and 11 clinical studies, were included for analysis. CONCLUSIONS: Most studies
      found a significant and measurable long-term effect of SVF-enhanced fat grafting
      on breast augmentation and defects, wound healing, scaring, and facial aesthetic
      outcomes. Stromal vascular fraction use did not result in a higher instance of
      complications and, thus, can be considered a safe option for fat grafting.

PMID- 30095544
TI  - Malignant Hyperthermia: From the OR to the Sidelines.

PMID- 30095543
TI  - Chest Trauma in Athletes.

PMID- 30095545
TI  - Inaugural HealthAccord Conference (SportAccord Convention, Bangkok, Thailand):
      The Power of Sport - The Power to Change.
AB  - SportAccord organized the inaugural HealthAccord conference on April 19, 2018, in
      Bangkok, Thailand. The goal of HealthAccord is for the International Sport
      Federations (IF) and sport industry leaders to address high-priority issues
      facing sport through a serious commitment to innovation to protect athlete
      health, to enhance athlete performance, and to stimulate action to improve global
      health through the promotion of physical activity. The first HeathAccord
      conference was organized by drawing on the knowledge and experience of experts
      from global health programs focused on athletes and global citizens,
      respectively. The first session, "The Power of Sport," addressed the application
      of "state of the art" sport science and sport medicine for the protection of
      athlete health and to enhance sport performance. "The Power of Sport" session
      concentrated on enabling athletes to perform spectacular feats that are "higher,
      stronger, faster" intended to engage and thrill global audiences without
      resorting to prohibited substances and methods, to enable athletes to remain
      active in sport for a longer career, and to increase the attraction of sport for
      sponsors. In the second session, "The Power to Change," sport was viewed as
      having an important role in promoting physical activity within their respective
      federations, community, and internationally. The Olympic movement, IF, and other
      sport stakeholders are urgently needed to become the social drivers to correct
      the mismatch between physical activity for health development and draw toward
      sedentary lifestyles of the modern world. Key outcomes of this first HealthAccord
      conference were the agreement among participants to develop an innovative and
      high-impact collaboration between IF and related stakeholders; to use sport as a
      social movement platform to measurably improve health, both for athletes and for
      global citizens.

PMID- 30095547
TI  - Tools Clinicians Can Use to Help Get Patients Active.
AB  - An epidemic of physical inactivity has given rise to a population struggling with
      early mortality and an increase in chronic non-communicable diseases such as
      cardiovascular disease, diabetes, and cancer. Primary care providers as well as
      other clinicians are in a position to help overcome this epidemic of physical
      inactivity. The goal of this commentary is to provide clinicians with resources
      and recommendations from the recent literature to help overcome barriers to
      physical activity counseling and help patients become physically active. Theory
      based interventions from communication and exercise prescriptions to wearables
      and mobile health technology are discussed. Limitations and future directions are
      explored.

PMID- 30095548
TI  - Association of pre-operative troponin levels with major adverse cardiac events
      and mortality after noncardiac surgery: A systematic review and meta-analysis.
AB  - BACKGROUND: Circulating cardiac troponin levels are powerful predictors of
      prognosis in many clinical settings, but their association with outcomes after
      noncardiac surgery is unclear. OBJECTIVES: The aim of this systematic review was
      to summarise current evidence on the association of pre-operative troponin
      elevation with postoperative major adverse cardiac events (MACE) and mortality in
      patients undergoing noncardiac surgery. DESIGN: Systematic review of
      observational studies with meta-analysis. DATA SOURCES: PubMed, EMBASE and
      Science Citation Index Expanded (ISI Web of Science) from their inception to 1
      October 2017. ELIGIBILITY CRITERIA: Observational studies reporting the
      associations between pre-operative troponin levels and MACE and all-cause
      mortality after noncardiac surgeries were included. RESULTS: Ten studies met the
      eligibility criteria. The entire body of evidence addressing the research
      question was based on a total of 10 371 patients: 4.7 to 68.3% (median 23.8%) of
      patients had elevated troponin levels before surgery. Elevated pre-operative
      troponin was significantly associated with short-term MACE (seven studies, 5180
      patients: odds ratio (OR) 6.92, 95% confidence interval (CI) 3.85 to 12.42),
      short-term mortality (five studies, 6103 patients: OR 4.23, 95% CI 2.27 to 7.89)
      and long-term mortality (two studies, 760 patients: OR 2.51, 95% CI 1.47 to
      4.29). The associations remained significant when only multivariate-adjusted
      results were analysed. Overall, the reviewers' certainty about the summary
      estimates of the associations was very low. CONCLUSION: Current evidence suggests
      that pre-operative high troponin levels are significantly associated with adverse
      cardiac events and mortality after noncardiac surgery. TRIAL REGISTRATION: This
      systematic review was registered in the International Prospective Register of
      Systematic Reviews (Centre for Reviews and Dissemination 42017077837).

PMID- 30095549
TI  - Efficacy and safety of dexmedetomidine in peripheral nerve blocks: A meta
      analysis and trial sequential analysis.
AB  - BACKGROUND: The duration of analgesia provided by nerve blocks is limited if
      local anaesthetics are administered alone. Therefore, several additives,
      including dexmedetomidine (DEX), have been investigated in order to prolong
      postoperative analgesia following single-shot regional anaesthesia. OBJECTIVES:
      The aim of this meta-analysis was to assess the efficacy and safety of the
      addition of perineural DEX to local anaesthetics compared with local anaesthetics
      alone or local anaesthetics combined with systemic administration of DEX. DESIGN:
      A systematic review of randomised controlled trials (RCT) with meta-analysis,
      trial sequential analysis and assessment of the quality of evidence by the GRADE
      approach. DATA SOURCES: The databases MEDLINE, CENTRAL and EMBASE (to May 2017)
      were systematically searched. ELIGIBILITY CRITERIA: All RCTs investigating the
      efficacy and safety of perineural DEX combined with local anaesthetics compared
      with local anaesthetics alone or local anaesthetics in combination with systemic
      DEX in peripheral nerve blocks of adults undergoing surgery were included.
      RESULTS: A total of 46 RCTs (3149 patients) were included. Patients receiving
      perineural DEX combined with local anaesthetics had a longer duration of
      analgesia than local anaesthetics alone [mean difference 4.87 h; 95% confidence
      interval (95% CI) 4.02 to 5.73; P < 0.001; I = 100%; moderate-quality evidence].
      The most important adverse events in the DEX group were intraoperative
      bradycardia [risk ratio 2.83; 95% CI 1.50 to 5.33; P = 0.035; I = 40%; very low
      quality evidence] and hypotension (risk ratio 3.42; 95% CI 1.24 to 9.48; P =
      0.002; I = 65%; very low quality evidence). In contrast, there were no
      differences in the duration of analgesia between perineural or intravenous DEX
      combined with local anaesthetics (mean difference 0.98 h; 95% CI -0.12 to 2.08; P
      = 0.08; I = 0%). CONCLUSION: This meta-analysis demonstrated that DEX in
      combination with local anaesthetics increases postoperative analgesia for around
      5 h. However, there are higher risks of intraoperative hypotension and
      bradycardia. Findings on side effects are associated with high uncertainty.
      Initial evidence suggests no difference in the duration of analgesia associated
      with systemic or perineural DEX. TRIAL REGISTRATION: CRD42016042486.

PMID- 30095546
TI  - Exercise is Medicine for Concussion.
AB  - Sport-related concussion (SRC) is a physiological brain injury that produces
      cerebral and systemic effects, including exercise intolerance. Exercise
      intolerance after concussion is believed to be the result of autonomic nervous
      system (ANS) dysfunction. Ventilation is inappropriately low for the level of
      exercise intensity, raising arterial carbon dioxide (PaCO2) levels. Elevated
      PaCO2 increases cerebral blood flow (CBF) out of proportion to exercise
      intensity, which is associated with symptoms that limit exercise performance.
      Thus, elevated exercise PaCO2 may signal incomplete recovery from SRC. This
      article reviews recent observational and experimental data and presents the
      evidence that subthreshold aerobic exercise normalizes the cerebrovascular
      physiological dysfunction and is "medicine" for patients with concussion and
      persistent postconcussive symptoms (PPCS). It discusses the systematic evaluation
      of exercise tolerance after concussion using the Buffalo Concussion Treadmill
      Test (BCTT) and reviews the utility of the Buffalo Concussion Bike Test (BCBT),
      the data from which are used to establish an individualized heart rate "dose" of
      subthreshold exercise to safely speed recovery, which also may work in the acute
      recovery phase after SRC with the potential to reduce the incidence of PPCS.
      Evaluation and treatment approaches based on the physiology of concussion suggest
      that exercise is medicine for concussion, potentially adding a new dimension to
      concussion care to help safely speed recovery and prevent PPCS in some patients.

PMID- 30095550
TI  - Effects of a single subanaesthetic dose of ketamine on pain and mood after
      laparoscopic bariatric surgery: A randomised double-blind placebo controlled
      study.
AB  - BACKGROUND: When administered as a continuous infusion, ketamine is known to be a
      potent analgesic and general anaesthetic. Recent studies suggest that a single
      low-dose administration of ketamine can provide a long-lasting effect on mood,
      but its effects when given in the postoperative period have not been studied.
      OBJECTIVE: We hypothesised that a single low-dose administration of ketamine
      after bariatric surgery can improve pain and mood scores in the immediate
      postoperative period. DESIGN: We performed a randomised, double-blind, placebo
      controlled study to compare a single subanaesthetic dose of ketamine (0.4 mg kg)
      with a normal saline placebo in the postanaesthesia care unit after laparoscopic
      gastric bypass and gastrectomy. SETTING: Single-centre, tertiary care hospital,
      October 2014 to January 2018. PATIENTS: A total of 100 patients were randomised
      into the ketamine and saline groups. INTERVENTION: Patients in the ketamine group
      received a single dose of ketamine infusion (0.4 mg kg) in the postanaesthesia
      care unit. Patients in the placebo groups received 0.9% saline. OUTCOME MEASURES:
      The primary outcome was the visual analogue pain score. A secondary outcome was
      performance on the short-form McGill's Pain Questionnaire (SF-MPQ). RESULTS:
      There were no significant differences in visual analogue pain scores between
      groups (group-by-time interaction P = 0.966; marginal group effect P = 0.137).
      However, scores on the affective scale of SF-MPQ (secondary outcome)
      significantly decreased in the ketamine group as early as postoperative day (POD)
      2 [mean difference = -2.2 (95% bootstrap CI -2.9 to 1.6), Bonferroni adjusted P <
      0.001], compared with placebo group in which the scores decreased only by POD 7.
      Scores on the total scale of SF-MPQ for the ketamine group were smaller compared
      with the placebo group (P = 0.034). CONCLUSION: Although there was no significant
      difference between ketamine and placebo for the primary outcome measure, patients
      who received ketamine experienced statistically and clinically significant
      improvement in their comprehensive evaluation of pain, particularly the affective
      component of pain, on POD 2. However, future studies are needed to confirm the
      enduring effects of ketamine on the affective response to postoperative pain.
      CLINICAL TRIAL REGISTRATION: NCT02452060. : This article is accompanied by the
      following Invited Commentaries:Mion G. Ketamine stakes in 2018. Right doses, good
      choices. Eur J Anaesthesiol 2019; 36:1-3.Robu B, Lavand'homme, P. Targeting the
      affective component of pain with ketamine. A tool to improve the postoperative
      experience? Eur J Anaesthesiol 2019; 36:4-5.

PMID- 30095551
TI  - Ultrasound assessment of gastric emptying time after a standardised light
      breakfast in healthy children: A prospective observational study.
AB  - OBJECTIVES: Current guidelines recommend 6 h of fasting for solids before
      anaesthesia. However, prolonged fasting may lead to discomfort, hunger, thirst,
      misbehaviour and lipolysis. To prevent this, a more liberal fasting regimen has
      been empirically implemented in our children's hospital, allowing a shorter
      fasting time of 4 h for a standardised light breakfast. AIM: The aim of this
      study was to determine the gastric emptying time after a standardised light
      breakfast in healthy children. DESIGN: A prospective observational
      noninterventional study. METHODS: After fasting overnight, the children had a
      standardised light breakfast. Before and afterwards, ultrasound examinations of
      the gastric antrum were performed hourly to determine the gastric antral area
      (GAA), which is a surrogate parameter for gastric volume in children in the right
      lateral position (RLP). Demographic data and fasting times are presented as mean
      +/- SD (range) and GAA as median (interquartile range). RESULTS: Twenty-two
      children aged 7.8 (2.5 to 13.6) years volunteered for this study. After fasting
      overnight [735 +/- 120 (467 to 930) min], the initial GAA was 3.06 (2.35 to 4.03)
      cm in RLP. After the light breakfast, GAA in RLP initially increased and
      decreased subsequently. After 4 h, GAA in RLP was lower than the initial value
      (median of differences -0.54, 95% confidence interval -1.00 to -0.07, P < 0.05).
      Correlation between GAA in RLP and fasting time was significant (r = -0.62, P <
      0.0001). Using a linear regression model, the calculated mean gastric emptying
      time after the standardised light breakfast was 211 min for GAA = 3.06 cm.
      CONCLUSION: The study showed a mean gastric emptying time of less than 4 h after
      a standardised light breakfast in children. These results encourage our current
      clinical practice and support the efforts towards a more liberal fasting regimen
      for light meals in paediatric anaesthesia. TRIAL REGISTRATION: German Registry of
      Clinical Studies (DRKS-ID: DRKS 00013893).

PMID- 30095552
TI  - Ranking Barriers, Motivators, and Facilitators to Promote Physical Activity
      Participation of Persons With Dementia: An Explorative Study.
AB  - BACKGROUND AND PURPOSE: Community-dwelling persons with dementia are inactive
      most of the day. The purpose of this study was to rank the barriers, motivators,
      and facilitators that hamper or promote physical activity (PA) participation for
      persons with dementia. This could provide knowledge that can be used to design
      effective interventions to promote PA participation for persons with dementia.
      METHODS: Twenty community-dwelling persons with dementia, mean (SD) age = 79
      (5.4) years, 25% female, mean (SD) Mini-Mental Status Examination score = 23
      (3.5); their informal caregivers, N = 20, mean (SD) age = 70 (11.5) years, 85%
      female; and an expert group of physiotherapists, N = 15, mean (SD) age = 41
      (12.4) years, 73% female, were asked to rank preselected barriers, motivators,
      and facilitators of PA participation for persons with dementia. These statements
      were categorized at the intrapersonal, interpersonal, and community levels.
      RESULTS AND DISCUSSION: Persons with dementia and their informal caregivers
      selected only motivators and facilitators as being important for PA
      participation, with the motivator "beneficial health effects" considered the most
      important. The experts had a different perspective on PA participation; half of
      their ranked top 10 most important factors were barriers to PA participation for
      persons with dementia. This could be explained by the more critical role of a
      therapist, focusing on symptom control and treatment of disability; in this case,
      the elimination of barriers to maintain PA participation in their patients.
      Furthermore, all groups prioritized statements at the intrapersonal level.
      CONCLUSIONS: The results of this study suggest a difference in perspective
      between the more optimistic view of persons with dementia and their informal
      caregivers and the more critical view of physiotherapy experts regarding the most
      important factors that influence PA participation. In addition, there was a
      strong focus on the individual characteristics that influence PA behavior that
      warrant personalized interventions to promote PA in dementia.

PMID- 30095553
TI  - Disability in amyotrophic lateral sclerosis compared with traumatic brain injury
      using the World Health Organization Disability Assessment Schedule 2.0 and the
      International Classification of Functioning minimal generic set.
AB  - We compared the functioning of two neurological patient groups, amyotrophic
      lateral sclerosis (ALS) and traumatic brain injury (TBI), using brief and
      validated International Classification of Functioning (ICF)-based tools. A 12
      item World Health Organization Disability Assessment Schedule (WHODAS 2.0)
      questionnaire was mailed to ALS and TBI patients and their significant others 2
      weeks before their appointment at an outpatient clinic of a university hospital.
      In addition, a neurologist filled in the ICF minimal generic set. Two years after
      diagnosis, no significant differences between the two diagnosis groups were found
      in overall functioning or in working ability using either patient or proxy WHODAS
      or physician-rated minimal generic set. In single items, however, clear
      differences were found. Patients and significant others rated household
      activities, mobility, and self-care as more impaired in the group with ALS, and
      learning, concentrating, and maintaining friendships in the group with TBI. There
      were no differences between the two diagnosis groups in the WHODAS items
      emotional functions, engaging in community, relating with strangers, or in
      working ability. Both brief ICF-based generic scales, WHODAS and the ICF generic
      set, could show differences between these patient groups with severe disability.
      The results of this study should promote assessment of disability with WHODAS 2.0
      in ALS and TBI.

PMID- 30095554
TI  - A Nurse's Perspective on Visual Rehabilitation of Outpatients With Low Vision in
      China.
AB  - PURPOSE: The purposes of the study were to analyze patient use and satisfaction
      with low vision aids (LVAs) at the Wenzhou Medical University Low Vision and
      Rehabilitation Center and to assess the promotion of visual rehabilitation
      services as a new responsibility for nurses in China. METHODS: Records of 178
      patients with low vision (LV) from the Low Vision and Rehabilitation Center
      examined between October 2015 and October 2016 included basic patient information
      (e.g., age, diagnosis, visual acuity, educational level) and use of LVAs
      (patients' own aids, daily duration of LVA use, or refusal to use aids). RESULTS:
      Sixty percent owned LVAs. Of these, 66% were obtained from a hospital, 26% were
      obtained from commercial stores, and others were obtained from government or
      gifts. Patients reported that use of LVAs was reduced because of visual fatigue
      (39%), inconvenience (22%), and lack of benefit (12%). Reasons for the 40% who
      had never used visual rehabilitation were nonreferral by doctors (76%), refusal
      because of inconvenience, discomfort and cosmetics (20%), or a preference for
      other treatments (4%). CONCLUSIONS: Greater awareness of LV rehabilitation by
      nurses, ophthalmologists, patients, and the public is necessary. Additional
      government support for LV rehabilitation is also required.

PMID- 30095555
TI  - Effectiveness and Predictors of Response to 1-Hz Repetitive Transcranial Magnetic
      Stimulation in Patients With Obsessive-Compulsive Disorder.
AB  - OBJECTIVE: The present study aimed to assess the effectiveness of repetitive
      transcranial magnetic stimulation (rTMS) treatment targeting either supplementary
      motor area (SMA) or orbitofrontal cortex (OFC) among patients with OCD in real
      world clinical practice settings. Also, the present study explored for potential
      predictors of response to rTMS treatment. METHODS: Retrospective review and
      analysis of records of 79 patients with medication-refractory OCD, all of whom
      had received 20 sessions of 1-Hz rTMS as part of routine clinical care. Of 79
      patients, 46 received rTMS over the bilateral SMA and 33 over the left OFC. A
      reduction of 25% and 35% in Yale-Brown Obsessive Compulsive Scale (YBOCS) scores
      was used to classify outcome as partial and complete response, respectively.
      Statistical analysis was done using SPSS version 23.0. RESULTS: There was a
      significant decrease in mean YBOCS score from baseline to end of treatment (7.68
      +/- 5.62; t = 12.14, P < 0.001). Forty-five patients (57%) met criteria for
      partial response, of which 32 patients (40.5%) showed complete response. There
      was no significant difference in outcomes between patients receiving rTMS over
      SMA or OFC. Binary logistic regression analysis revealed presence of comorbid
      depression and higher baseline YBOCS score to be associated with lesser
      likelihood of response to rTMS. CONCLUSIONS: This study provided evidence for
      overall effectiveness of adjunctive 1-Hz rTMS treatment over either SMA or OFC in
      patients with medication-refractory OCD, and reported comorbid depression and
      higher pretreatment YBOCS scores as potential predictors of poor response to
      rTMS.

PMID- 30095556
TI  - Electroconvulsive Therapy in the Presence of an Auditory Osseointegrated Implant.

PMID- 30095557
TI  - Functional Neurological Symptom Disorder Spontaneously Remits After
      Electroconvulsive Therapy.

PMID- 30095558
TI  - Three-Dimensional High-Resolution Black-Blood Magnetic Resonance Imaging for
      Detection of Arteritic Anterior Ischemic Optic Neuropathy in Patients With Giant
      Cell Arteritis.
AB  - OBJECTIVES: Arteritic anterior ischemic optic neuropathy (A-AION) caused by
      inflammatory occlusion of the posterior ciliary arteries is the most common
      reason for irreversible vision loss in patients with giant cell arteritis.
      Atypical clinical presentation and negative funduscopy can delay systemic high
      dose corticosteroid therapy to prevent impending permanent blindness and
      involvement of the contralateral eye.The purpose of this study was to assess the
      diagnostic accuracy of 3-dimensional (3D) high-resolution T1-weighted black-blood
      magnetic resonance imaging (T1-BB-MRI) for the detection of posterior ciliary
      artery involvement in patients with giant cell arteritis and funduscopic A-AION.
      MATERIALS AND METHODS: After institutional review board approval and informed
      consent, 27 patients with suspected giant cell arteritis and vision disturbances
      were included in this monocentric prospective cohort study. Giant cell arteritis
      was diagnosed in 18 patients according to the diagnostic reference standard (6
      men, 73.8 [69.0-78.0] years); 14 of those were positive for A-AION. Precontrast
      and postcontrast 3D T1-BB-MRI was performed in all 27 patients. Two radiologists
      separately assessed image quality and local fat suppression (4-point scale),
      visual contrast enhancement (3-point scale), and diagnostic confidence (5-point
      scale) regarding arteritic posterior ciliary artery involvement. Magnetic
      resonance imaging findings were assessed in comparison to funduscopy. Statistical
      analysis included accuracy parameters and interrater agreement. RESULTS:
      Sensitivity of 3D T1-BB-MRI was 92.9% (95% confidence interval, 66.1%-99.8%) and
      specificity was 92.3% (95% confidence interval, 64.0%-99.8%) for detection of A
      AION-positive patients. Image quality and local fat suppression were assessed
      with 3.2 +/- 0.8 (median 3) and 3.8 +/- 0.5 (median 4). Visual contrast
      enhancement with 2.3 +/- 0.8 (median 3) and diagnostic confidence was rated at
      4.7 +/- 0.5 (median 5). Interrater agreement was high (kappa = 0.85, P < 0.001).
      Three-dimensional T1-BB-MRI displayed bilateral findings in 50% of the cases,
      whereas only unilateral A-AION was detected in funduscopy as a possible
      indication for the contralateral eye at risk. CONCLUSIONS: Three-dimensional T1
      BB-MRI allows accurate detection of arteritic posterior ciliary artery
      involvement in patients with A-AION. Further, 3D T1-BB-MRI seems to display
      arteritic involvement of the posterior ciliary arteries earlier than funduscopy
      and might, therefore, display "vision-at-risk" in patients with visual impairment
      and suspected giant cell arteritis but unremarkable funduscopy.

PMID- 30095559
TI  - Melatonin Treatment of Visual Hallucinations in Parkinson Disease.

PMID- 30095560
TI  - Development of a Foundations of Simulation Teaching Course for Nurse Educators.
AB  - Academic leaders in a college of nursing were faced with an increasing need to
      integrate high quality simulations into their undergraduate curriculum; however,
      there was a general lack of expertise in the subject area among faculty. The
      leaders supported the development of an online course that focused on improving
      foundational simulation knowledge. The course, developed through collaboration
      between a faculty simulation expert and an instructional designer, was
      specifically designed to focus on key simulation objectives to improve the
      simulation skill set of faculty. Posttest scores revealed an increase in
      simulation knowledge.

PMID- 30095561
TI  - Which Early Childhood Experiences and Skills Predict Kindergarten Working Memory?
AB  - OBJECTIVE: We examined how empirically and theoretically important predictors
      help explain the development of kindergarten working memory, an understudied
      predictor of school readiness and adjustment to schooling in early childhood. Our
      specific aim was to examine the extent to which antecedents, opportunity, and
      propensity variables directly and indirectly predict working memory development.
      METHODS: We conducted structural equation modeling on a nationally representative
      and longitudinal sample of 14,000 kindergarten students. Predictors of end-of
      kindergarten working memory include parent reports of antecedent variables such
      as socioeconomic status, mother's marital status, breastfeeding, child's age, and
      perception of child learning skills; teacher reports of opportunity variables
      including the frequency children read aloud and counted in their kindergarten
      class and classroom climate; and direct assessments of child propensity variables
      including earlier working memory, cognitive fluidity, teacher reports of child
      self-regulation, and math and reading knowledge. RESULTS: Together, childhood
      antecedents, opportunity, and propensity latent factors contributed to 41% of the
      variance of kindergarten working memory. Child propensity had a significant
      direct effect on child working memory, whereas antecedent and opportunity factors
      had significant indirect effects on working memory through child propensity.
      CONCLUSION: In this study, we identify several modifiable variables that directly
      and indirectly predict child working memory skills using a large population-based
      sample. Better understanding of how child-, family-, and school-level variables
      contribute to the development of working memory in young children can be seen as
      an important step in the creation of preventive interventions designed to improve
      these important skills.

PMID- 30095562
TI  - Nomograms in urologic oncology, advantages and disadvantages.
AB  - PURPOSE OF REVIEW: To critically review the current literature regarding the
      recently published nomograms in urologic oncology and to examine the advantages
      and disadvantages of their application. RECENT FINDINGS: Several nomograms have
      been developed in the field of urologic oncology over the recent years, to
      improve clinical decision-making and patients counseling. In the current review,
      we examined 6 nomograms on prostate cancer, 9 nomograms on kidney cancer and 8
      nomograms on bladder cancer that have been recently published. Most of the
      examined nomograms lack external validation and very few have investigated the
      clinical utility of any given model, as measured by its ability to improve
      clinical decision-making. Two studies relied on genomic classifiers and showed up
      to 6% improved accuracy compared with the models based only on clinical
      variables. However, these new tools were limited by elevated cost and scarce
      availability of these new biomarkers, which may represent barriers toward future
      use. SUMMARY: Several nomograms have been developed in these recent years in
      urologic oncology. All exhibited elevated accuracy, good calibration and
      promising decision analyses, when they were internally validated. However,
      external validations and assessment of clinical utility are needed before they
      can be incorporated into routine clinical practice.

PMID- 30095563
TI  - The More Things Change: Buprenorphine/naloxone Diversion Continues While
      Treatment Remains Inaccessible.
AB  - OBJECTIVES: Buprenorphine/naloxone, an evidence-based treatment for opioid use
      disorder, is sometimes diverted for non-medical use. In Rhode Island, the
      prevalence of opioid use and, more recently, of fentanyl in the illicit drug
      supply is driving overdose fatalities, which increases the need for treatment and
      raises questions about the changing role of diverted medication in shaping
      overdose risk. METHODS: This study considered data from 2 Rhode Island based
      studies (conducted in 2009 and 2016, respectively) of people who use illicit or
      diverted prescription opioids and their patterns of buprenorphine/naloxone
      diversion. Using targeted sampling, individuals who use opioids completed a brief
      questionnaire about their drug use. For the 2016 study, logistic regression was
      used to identify associations with recent and lifetime use of diverted
      medication. RESULTS: A total of 128 individuals who use opioids non-medically
      participated in the 2016 study. Of these, 38% (n = 13) reported diverted
      buprenorphine/naloxone use in the past 2 months, similar to the pattern observed
      in 2009 (41%, n = 41). Common motivations for using diverted medication included
      the management of withdrawal symptoms (40%, n = 35) and self-treatment of opioid
      use disorder (39%, n = 34). Few reported using to "get high" (12%, n = 4).
      Seeking buprenorphine/naloxone treatment in the previous 12 months was positively
      associated with using diverted medication in the past 2 months (odds ratio =
      5.14, 95% confidence interval = 1.0-26.5, P = 0.05). Participants of both studies
      reported the same barriers to care in 2009 and 2016. CONCLUSION: The use of
      diverted/buprenorphine remains common among people who use opioids non-medically
      and indicates a severe shortage in treatment capacity and inaccessibility of
      existing services.

PMID- 30095564
TI  - Commentary on "The More Things Change: Buprenorphine/Naloxone Diversion Continues
      While Treatment is Inaccessible".
AB  - : This commentary puts the recent findings by Carroll et al into historical
      perspective, noting both the long-held problem of medication diversion when
      pharmacotherapy access is limited, and the ways in which medication diversion
      concerns and regulations help create those treatment access barriers. Recent
      efforts to bridge the treatment gap, including increases in Federal funding
      through the 21st Century Cures Act and expanding the buprenorphine patient cap
      and scope of eligible providers under the Comprehensive Addiction Recovery Act
      (CARA) will likely help; however, important structural barriers remain. Health
      insurance barriers, including limited Medicaid coverage, combined with stigma
      against pharmacotherapy persist, which likely means that people in need of
      treatment will continue to self-treat their symptoms with diverted medications,
      such as the buprenorphine/naloxone use noted by Carroll and colleagues.

PMID- 30095565
TI  - Pharmacotherapy, Resource Needs, and Physician Recruitment Practices in Substance
      Use Disorder Treatment Programs.
AB  - OBJECTIVES: Effective pharmacological treatments for opioid use disorder (OUD)
      continue to be underutilized, particularly within specialty substance use
      disorder (SUD) treatment organizations. Few studies have examined whether
      specific practices to recruit prescribers, financial needs, and human resource
      needs facilitate or impede the implementation of pharmacotherapy. METHODS:
      Surveys were completed by administrators from 160 treatment programs in Florida,
      Ohio, and Wisconsin. Respondents described availability of five pharmacotherapies
      for treating OUD, organizational resource needs, current use of physician
      recruitment practices, and buprenorphine treatment slots. RESULTS: The mostly
      commonly available medications were injectable naltrexone (65.4%; n = 102),
      buprenorphine-naloxone (55.7%; n = 88), and tablet naltrexone (50.0%; n = 78).
      Adopters of each of the 5 pharmacotherapies reported significantly greater
      physician outreach than organizations that did not provide these medications. The
      mean number of buprenorphine slots was 94.1 (SD 205.9). There were unique
      correlates of adoption (ie, any slots) and availability (number of slots) of
      buprenorphine. Physician outreach activities were correlated with the likelihood
      of nonadoption, whereas medical resource needs (ie, needing more physicians to
      prescribe pharmacotherapy) and dedicated resources for physician recruitment were
      associated with the number of slots. CONCLUSIONS: Physician recruitment
      activities differentiated those organizations that had existing pharmacotherapy
      treatment capacity (ie, any slots) from those that had no capacity. Efforts to
      address the medical resource needs of treatment organizations, and also
      strategies that encourage organizations to devote resources to recruiting
      prescribers may hold promise for increasing access to these lifesaving
      treatments.

PMID- 30095566
TI  - Commentary: Addressing Workforce Needs for Medication Treatment of Opioid Use
      Disorder.
AB  - : Medication treatment of opioid use disorder (OUD) is recognized as an effective
      evidence-based treatment. It has been underused, in part due to challenges in
      recruiting and retaining a provider workforce that is able to prescribe and
      manage patients treated with OUD medications. A national goal should be: anyone
      with an OUD must have adequate access to a range of medications for treatment and
      support, provided in high-quality settings, and all programs receiving public or
      private funding should be so equipped. To accomplish this, it is important to
      understand what recruitment efforts are most successful, and what implementation
      strategies and service models are most effective. Building an adequate OUD
      treatment workforce, however, will require a system with adequate program
      resources and incentives, clinician and patient education to reduce stigma,
      limited regulatory burden, and adequate reimbursement and support high-quality
      services.

PMID- 30095567
TI  - Nonmedical Use of Stimulants Is Associated With Riskier Sexual Practices and
      Other Forms of Impulsivity.
AB  - BACKGROUND: This study sought to examine the occurrence of the nonmedical use of
      prescription stimulants (amphetamines and methylphenidate) in a university sample
      and their associated physical and mental health correlates, including potential
      relationships with risky sexual practices. METHODS: A 156-item anonymous online
      survey was distributed via e-mail to a sample of 9449 university students.
      Current use of alcohol and drugs, psychological and physical status, and academic
      performance were assessed, along with questionnaire-based measures of impulsivity
      and compulsivity. RESULTS: A total of 3421 participants (59.7% female) were
      included in the analysis. 6.7% of the sample reported current/recent nonmedical
      use of prescription stimulants, while an additional 5.8% reported misuse in the
      past. Nonmedical use of prescription stimulants was associated with lower grade
      point averages, and with taking a broad range of other drugs (including alcohol,
      nicotine, illicit substances, and consumption of caffeinated soft drinks).
      Nonmedical use of stimulants was also significantly associated with impulsivity
      (Barratt scale), prior treatment for substance use problems, and elevated
      occurrence of disordered gambling, post-traumatic stress disorder, and anxiety;
      but not depression symptoms or binge-eating disorder (though it was associated
      with using drugs to lose weight). The relationship with probable attention
      deficit/hyperactivity disorder (ADHD) on screening was not significant but was
      numerically elevated. Finally, those using nonmedical prescribed stimulants were
      significantly more sexually active (including at a younger age), and were less
      likely to use barrier contraception. CONCLUSIONS: Nonmedical use of prescription
      stimulants is common in young adults and has profound public health associations
      including with a profundity of other drug use (licit and illicit), certain mental
      health diagnoses (especially gambling, anxiety, and post-traumatic stress
      disorder ), worse scholastic performance, and riskier sexual practices. The
      majority of people with nonmedical use of prescription stimulants do not have
      ADHD, and its link with current ADHD symptoms was less marked than for certain
      other disorders. Clinicians should screen for the misuse of prescription
      stimulants as they may be associated with a range of problematic behaviors. Risk
      of diversion (which may be higher for those living in shared accommodation and
      those with substance use disorder history) merits careful assessment before
      prescribing stimulant medication.

PMID- 30095568
TI  - Craniofacial Flash: Minimizing Radiation Dose in Pediatric Craniofacial Computed
      Tomography.
AB  - BACKGROUND AND PURPOSE: The routine use of computed tomography (CT) in evaluation
      of pediatric craniofacial abnormalities is controversial. While there are
      benefits to preoperative imaging, there are risks related to ionizing radiation
      and sedation/anesthesia. In this study, the authors describe their experience
      with a new craniofacial CT protocol (Craniofacial-Flash) that provides bone
      detail equivalent to conventional CT, while delivering a substantially lower
      radiation dose and reducing the scan time to obviate the requirement of
      sedation/anesthesia. METHODS: Following IRB approval, dose identification and
      image analysis were conducted retrospectively on all patients who underwent
      craniofacial CT using either the conventional protocol or Craniofacial-Flash
      protocol between November 2013 and September 2015. Image analysis consisted of
      automated segmentation of bone and soft tissue, followed by noise interpretation
      of each study segment. RESULTS: The conventional CT group included 175 patients
      (mean age 6.38 years) with a median dose length product of 243.00 mGy.cm. The
      Craniofacial-Flash CT group included 208 patients (mean age 3.31 years) with
      median dose length product of 27.60 mGy.cm. Image quality was equivalent for
      bone, with coefficient of variation values of 0.20 for the conventional CT group
      and 0.21 for the Craniofacial-Flash group. Soft tissues coefficients of variation
      were disparate at 0.07 for conventional CT and 0.14 for Craniofacial-Flash
      protocol. CONCLUSION: The Craniofacial-Flash protocol reliably generates
      craniofacial bone images adequate for routine use in craniofacial practice, while
      reducing the radiation dose by 88.87% compared with a conventional craniofacial
      CT scan, and eliminating the need for sedation.

PMID- 30095569
TI  - National Longitudinal Comparison of Patients Undergoing Surgical Management of
      Craniosynostosis.
AB  - PURPOSE: Limited cross-institutional studies compare strip craniectomy versus
      cranial vault remodeling (CVR) for craniosynostosis management. Given competing
      surgical preferences, the authors conducted a large-scale analysis of
      socioeconomic differences, costs, and complications between treatment options.
      METHODS: Nonsyndromic craniosynostosis patients receiving strip craniectomies or
      CVR were identified in the Kids' Inpatient Database for years 2000 to 2009.
      Demographics, socioeconomic background, hospital characteristics, charge, and
      outcomes were tabulated. Univariate and multivariate analyses were performed for
      comparison. RESULTS: Two hundred fifty-one strip craniectomies and 1811 CVR
      patients were captured. Significantly more strip craniectomy patients were White
      while more CVR patients were Hispanic or Black (P < 0.0001). Strip craniectomy
      patients more often had private insurance and CVR patients had Medicaid (P <
      0.0001). Over time, CVR trended toward treating a higher proportion of Hispanic
      and Medicaid patients (P = 0.036). Peri-operative charges associated with CVR
      were $27,962 more than strip craniectomies, and $11,001 after controlling for
      patient payer, income, bedsize, and length of stay (P < 0.0001). Strip
      craniectomies were performed more frequently in the West and Midwest, while CVR
      were more common in the South (P = 0.001). Length of stay was not significant.
      Postsurgical complications were largely equivocal; CVR was associated with
      increased accidental puncture (P = 0.025) and serum transfusion (P = 0.002).
      CONCLUSION: Our national longitudinal comparison demonstrates widening
      socioeconomic disparities between strip craniectomy and CVR patients. Cranial
      vault remodeling is more commonly performed in underrepresented minorities and
      patients with Medicaid, while strip craniectomy is common in the White population
      and patients with private insurance. While hospital charges and complications
      were higher among CVR, differences were smaller than expected.

PMID- 30095570
TI  - Seasonal Variations in Microtia of Chinese Population.
AB  - BACKGROUND: Seasonality of congenital birth defect could help to identify
      environmental risk factors. Data concerning the seasonality of the prevalence of
      microtia are little. This article aims to determine whether births of microtia
      follow a certain pattern. METHODS: Data were obtained from 2669 patients with
      microtia who were admitted to Second Ear Reconstruction Center of Plastic Surgery
      Hospital, Chinese Academy of Medical Science from January 2007 to December 2013.
      The controls consist of all living births from the Obstetric Department of the
      Haidian Maternal & Child Health Hospital during the same time. Seasonal
      variations in months of births were analyzed by using chi test. RESULTS: A total
      of 2669 patients with microtia and 89,273 healthy living newborns were included
      in this study. Birth time peak of the patients occurred in autumn, especially in
      November, compared with the nadir in the spring, especially in April (P G 0.05).
      The birth time peak of male patients occurred in autumn, too, especially in
      October and November, While the valley occurred in spring (April, too). However,
      the seasonality in female patients is not so apparent with the peak occurred in
      the tail of summer and autumn, especially in August, November, and September
      orderly, while the valley occurred in March. CONCLUSIONS: There is a possible
      seasonality in birth months and a difference between sexes of patients with
      microtia in this native Chinese population. This approach could be useful to
      study the etiology of microtia.

PMID- 30095571
TI  - Missing Data, Data Cleansing, and Treatment From a Primary Study: Implications
      for Predictive Models.

PMID- 30095572
TI  - NENIC's 2018 Trends in Clinical Informatics: A Nurse's Perspective.

PMID- 30095573
TI  - Exploring Research Topics and Trends in Nursing-related Communication in
      Intensive Care Units Using Social Network Analysis.

PMID- 30095574
TI  - Early Infant Risk Factors for Pediatric Eosinophilic Esophagitis.
AB  - OBJECTIVES: Eosinophilic esophagitis (EoE) is an inflammatory, atopic disease of
      the esophagus without a clear etiology. Our objective was to identify exposures
      and conditions in early infancy associated with the development of EoE. METHODS:
      A case-control study was performed using the Military Health System Database.
      Subjects diagnosed with EoE from October 2008 to September 2015 were matched 1:2
      on age and sex. Early infant risk factors from the first 6 months of life were
      investigated. RESULTS: A total of 1410 cases with EoE were matched to 2820
      controls. The median (interquartile range) age at diagnosis of EoE was 4.2 years
      (2.1-7.2) and 68.7% were boys. Proton pump inhibitors (adjusted odds ratio [aOR],
      2.73; 95% confidence interval [CI] 1.93-3.88), histamine-2 receptor antagonists
      (aOR, 1.64; 95% CI 1.27-2.13), and antibiotics (aOR, 1.31; 95% CI 1.10-1.56) were
      associated with EoE. Prematurity (aOR, 1.46; 95% CI 1.12-1.89) and early
      manifestations of atopic disease such as milk protein allergy (aOR, 2.37; 95% CI
      1.26-4.44) and eczema (aOR, 1.97; 95% CI 1.64-2.36) were related to increased
      odds for EoE. Erythema toxicum in infancy was strongly associated with a
      diagnosis of EoE (aOR 3.52; 95% CI 1.03-12.04). Infants with feeding difficulty
      (aOR, 1.45; 95% CI 1.18-1.77) and gastroesophageal reflux disease (aOR, 1.79; 96%
      CI 1.43-2.26) were also at increased risk for EoE. CONCLUSIONS: Acid-blocking
      medications and antibiotics during infancy were associated with later diagnosis
      of EoE. Erythema toxicum neonatorum, an eosinophilic immune phenomenon, was
      strongly associated with EoE. Identifying early infant risk factors for EoE may
      help to risk stratify the need for endoscopy.

PMID- 30095575
TI  - Parent-child Agreement on Health-Related Quality of Life in Children With
      Functional Constipation in Primary Care.
AB  - OBJECTIVE: Functional constipation (FC) has a major impact on the health-related
      quality of life (HRQoL) of children. The aim of this study was to evaluate parent
      child agreement on HRQoL in children (8-17 years) with FC in primary care.
      METHODS: Children diagnosed with FC by their clinician were eligible. HRQoL was
      measured with the Defecation Disorder List (DDL, score 0-100), and the EuroQol-5
      Dimension-Youth Visual Analogue Scale (EQ-5D-Y-VAS, scale 0-100). Parent-child
      agreement was examined with discrepancy scores, intraclass correlation
      coefficients and Bland-Altman plots. RESULTS: Fifty-six children, median age of
      10 years (IQR 8-12) and their parents were included. Parent-child agreement at a
      group level was good, with an intraclass correlation coefficient of 0.80 (95%
      confidence interval 0.67 to 0.88) for the DDL, and 0.78 (95% confidence interval
      0.65 to 0.87) for the EQ-5D-Y-VAS. Mean discrepancy scores for the DDL and EQ-5D
      Y-VAS were small: -2.6 and -2.9, implying that parents were slightly more
      positive about the HRQoL than their children. Bland-Altman plots showed
      considerable discordance between individual parent-child pairs. Limits of
      agreement were -19.7 and 14.6 for the DDL and -27.6 and 21.8 for the EQ-5D-Y-VAS.
      CONCLUSIONS: There is good parent-child agreement on HRQoL in children with FC at
      group level. However, a substantial number of parent-child pairs differed
      considerably on their rating of the HRQoL of the child. Therefore, we recommend
      clinicians, if they want to have an impression of the impact of the FC on the
      HRQoL of the child, to ask both the child and the parent(s).

PMID- 30095576
TI  - Increasing Vitamin D Serum Levels Is Associated with Reduced Pulmonary
      Exacerbations in Patients with Cystic Fibrosis.
AB  - CONTEXT: In 2012, The North American CF Foundation published new guidelines for
      the treatment of vitamin D deficiency in individuals with CF. OBJECTIVE: The
      objectives of our study were to assess the efficacy of these guidelines, and to
      test the effect of increasing vitamin D dosage on pulmonary function and
      exacerbations. DESIGN: Pulmonary function tests and serum concentrations of 25
      hydroxyvitamin D [25(OH)D] were measured one year prior to increasing vitamin D
      dosage according to the guidelines and at least one year later. In addition, days
      of hospitalization (DOH) and pulmonary exacerbations (PE) were counted and an
      average per year (DOHA and PEA, respectively) was calculated. SETTING AND
      PARTICIPANTS: 90 patients from The CF Clinic at Hadassah Mount-Scopus Hospital,
      Jerusalem, Israel. RESULTS: The mean serum concentration of vitamin D increased
      significantly from 20.97 ng/ml (52.34 nmol/L) at baseline to 25.41 ng/ml (63.42
      nmol/L) at the end of follow-up (p < 0.001). The number of PEA decreased
      significantly from 2.79 +/- 3.96 to 2.15 +/- 2.91 (p = 0.007). The change in
      vitamin D levels was correlated with a decrease in PEA (correlation coefficient =
      -0.318, p = 0.002). CONCLUSIONS: The NACFF guidelines for management of vitamin D
      deficiency improve vitamin D levels in patients with CF but did not reach the
      normal values in most patients. However, the increase in vitamin D serum levels
      was associated with a decrease in number of pulmonary exacerbations.

PMID- 30095577
TI  - Prognosis of Biliary Atresia After 2-year Survival With Native Liver: A
      Nationwide Cohort Analysis.
AB  - OBJECTIVES: The aim of the study is to determine the prognosis of patients with
      biliary atresia after 2 years of native liver survival (NLS) and to identify
      prognostic factors for continued NLS after 2 years of age. METHODS: We
      retrospectively analyzed perioperative, laboratory, and outcome parameters of all
      biliary atresia patients in The Netherlands between January 1987 and June 2015
      with NLS of at least 2 years. We compared parameters between patients who
      continued to have their native liver (NLS+) to those who did not, either by
      transplant or death (NLS-). RESULTS: We included 100 patients. Upon a median
      follow-up of 16.4 years, NLS ended in 37% by liver transplantation (LTx) and in
      6% by (pre-transplant) mortality. NLS rates at 5, 10, 15, 18 years of age were
      89%, 72%, 60%, 54%, respectively. Corresponding overall survival rates were 98%,
      90%, 87%, 87%, respectively. Six months post-Kasai, NLS+ patients had higher
      clearance of jaundice (COJ) rate, significantly lower total and direct serum
      bilirubin, aspartate-aminotransferase and alkaline phosphatase levels, compared
      with NLS- patients (each P < 0.05). Cox regression could only assess a
      significant effect of COJ on continued NLS. Main indications for LTx after the
      age of 2 were irreversible jaundice and portal hypertension. CONCLUSIONS: Eighty
      seven percent of patients with 2-year NLS reach adult age and more than 50% with
      their native liver. A pre-transplant mortality of 6%, however, exists among
      patients who reach the age of 2 years with their native livers. Early life
      parameters, other than COJ, did not have a significant effect on continued NLS
      after 2 years of age.

PMID- 30095578
TI  - Incidence and Clinical Features of Autoimmune Hepatitis in the Province of Santa
      Fe (Argentina).
AB  - OBJETIVES: The aim of the study is to investigate the incidence and clinical
      features of autoimmune hepatitis (AIH) in children from the province of Santa Fe,
      Argentina, for 10 years. METHODS: From the records of all of the pediatric
      hepatologists in the province of Santa Fe, Argentina, we reviewed the clinical
      charts of patients <18 years who were diagnosed with AIH (simplified score >6
      points) and followed between January 2003 and December 2013. Population data were
      extracted from the 2010 national census. Values were expressed as percentages and
      median +/- interquartile range. Mann-Whitney U test was used for comparison
      between the groups. RESULTS: Sixty-seven patients fulfilled inclusion criteria,
      from which 11 (16%) were later reclassified as having "autoimmune sclerosing
      cholangitis" according to biochemical, histological, and radiological findings. A
      final sample of 56 patients (39 F) with AIH was analyzed, giving an annual
      incidence of 0.56/100,000. Median age at presentation was 8 (5.7-11) years, and
      the median follow-up was 4 (2-7) years. Type 1 AIH was diagnosed in 89%. An acute
      presentation was observed in 53%, while 13 (23%) showed cirrhosis on initial
      biopsy. Prednisone (87%) and azathioprine (60%) were the most common drugs
      prescribed. At the end of follow-up, 53/56 (95%) were alive, including 4 patients
      (7%) who underwent liver transplantation. CONCLUSIONS: AIH has an estimated
      incidence of 0.56/100,000 per year in children from the province of Santa Fe
      (Argentina). Overall survival rate was 95%. A subgroup of patients diagnosed as
      AIH develops predominant biliary disease and should be better classified as
      autoimmune sclerosing cholangitis.

PMID- 30095579
TI  - Acute Kidney Injury May Not Be As Uncommon As Believed In Children With Advanced
      Chronic Liver Diseases.

PMID- 30095580
TI  - Professional growth is a personal responsibility.

PMID- 30095581
TI  - Getting accountability right.

PMID- 30095582
TI  - Mapping the frontal alpha asymmetry indicators of habitual emotion regulation: a
      data-driven approach.
AB  - Frontal alpha asymmetry (FAA) has been explored extensively in affective
      neuroscience. To determine which FAA indicators are linked with the habitual use
      of emotion regulation, we recorded the resting electroencephalogram alpha
      activity. First, we reduced all of the FAA indicators to four factors by
      exploratory factor analysis. Next, we carried out a multiple regression analysis
      to determine which factors could significantly predict the habitual use of
      emotion-regulation strategies. According to the results, greater left-asymmetric
      activation at the dorsolateral prefrontal cortex predicted increased use of
      reappraisal, whereas at the ventrolateral prefrontal cortex, it was predicted by
      right-asymmetric activation. Greater left-asymmetric frontal activity at the
      posterior dorsolateral prefrontal cortex was related to increased use of
      distraction and suppression. These results suggest that resting FAA in the
      prefrontal cortex region plays a significant role in the habitual use of emotion
      regulation.Video abstract: http://links.lww.com/WNR/A485.

PMID- 30095583
TI  - Plumbagin inhibits amyloid-beta-induced neurotoxicity: regulation of oxidative
      stress and nuclear factor erythroid 2-related factor 2 activation.
AB  - beta-Amyloid (Abeta) species probably exert neurotoxic effects in Alzheimer's
      disease. In the present study, the effect of antioxidant plumbagin was tested
      against Abeta25-35-induced neurotoxicity in the SH-SY5Y cell line. Cell viability
      was determined using an MTT assay. Antioxidant status was analyzed through
      antioxidant enzyme activities, nuclear factor erythroid 2-related factor 2 (Nrf
      2), and its downstream protein expressions. Inflammatory response was determined
      through nuclear factor-kappaB (NF-kappaB) pathway and cytokine expressions.
      Abeta25-35 showed a decrease in cell viability in a concentration-dependent
      manner. The IC50 value was found to be 17 uM. Pretreatment with plumbagin
      prevented Abeta25-35-induced toxicity by improving the cell viability up to 96%.
      Plumbagin inhibited Abeta25-35-induced oxidative stress by decreasing reactive
      oxygen species and lipid peroxidation. Abeta25-35-induced redox imbalance caused
      decreased Nrf-2 expression, with downregulation Nrf-2 target proteins heme
      oxygenase 1 and NAD(P)H dehydrogenase (quinone 1) during Abeta25-35 treatment.
      However, plumbagin improved the antioxidant defense system by increasing Nrf-2
      expression with concomitant upregulation in heme oxygenase 1 and NAD(P)H
      dehydrogenase (quinone 1). Abeta25-35 induced inflammatory response through
      upregulated NF-kappaB, cyclooxygenase-2, and inducible nitric oxide synthase
      levels. Plumbagin exerted anti-inflammatory effects by decreasing NF-kappaB,
      cyclooxygenase-2, and inducible nitric oxide synthase levels. Abeta25-35-induced
      increases in proinflammatory cytokine (interleukin-8, interleukin-6, and monocyte
      chemoattractant protein-1) expressions were suppressed by plumbagin pretreatment.
      Altogether, the present study indicates that plumbagin prevents redox status and
      inflammatory activation during Abeta25-35-induced toxicity by modulating the
      antioxidant defense system and Nrf-2 signaling.

PMID- 30095585
TI  - Meta-Analysis Reveals the Association Between Male Occupational Exposure to
      Solvents and Impairment of Semen Parameters.
AB  - OBJECTIVES: Solvent exposure is among the most common occupational exposures to
      chemical toxicants; data about the impact of such exposure on semen parameters
      are contradictory. We conducted the first meta-analysis to evaluate the risk of
      alteration in semen parameters related to occupational exposure to solvents.
      METHODS: From the PubMed database, we selected studies analyzing the semen of
      subjects occupationally exposed to solvents, compared with unexposed controls.
      The meta-analysis was performed on the various semen parameters analyzed in both
      populations. RESULTS: Seven studies were included in the study. The meta-analysis
      revealed a significant decrease in ejaculate volume [standardized mean difference
      (SMD) = -0.35 (-0.63 to -0.07)] and sperm concentration [SMD = -0.36 (-0.64 to 
      0.08)] in workers exposed to solvents compared with unexposed controls.
      CONCLUSION: Our results highlight the importance of preventing reprotoxic risks
      to male fertility in the workplace.

PMID- 30095584
TI  - Percutaneous coronary intervention or coronary artery bypass graft in left main
      coronary artery disease: a comprehensive meta-analysis of adjusted observational
      studies and randomized controlled trials.
AB  - BACKGROUND: Treatment of patients with ULMCA (unprotected left main coronary
      artery disease) with percutaneous coronary intervention (PCI) has been compared
      with coronary artery bypass graft (CABG), without conclusive results. METHODS:
      All randomized controlled trials (RCTs) and observational studies with
      multivariate analysis comparing PCI and CABG for ULMCA were included. Major
      cardiovascular events (MACEs, composite of all-cause death, MI, definite or
      probable ST, target vessel revascularization and stroke) were the primary end
      points, whereas its single components were the secondary ones, along with stent
      thrombosis, graft occlusion and in-hospital death and stroke. Subgroup analyses
      were performed according to Syntax score. RESULTS: Six RCTs (4717 patients) and
      20 observational studies with multivariate adjustment (14 597 patients) were
      included. After 5 (3-5.5) years, MACE rate was higher for PCI [odds ratio (OR)
      1.10, 95% confidence interval (CI) 1.07-1.14], without difference in death,
      whereas more relevant risk of MI was because of observational studies. Coronary
      stenting increased risk of revascularization (OR 1.52; 95% CI 1.34-1.72). At meta
      regression, performance of PCI was improved by use of intra-coronary imaging and
      worsened by first generation stents, whereas two arterial grafts increased
      benefit of CABG. For patients with Syntax score less than 22, MACE rates did not
      differ, whereas for higher values, CABG reduced MACE because of lower risk of
      revascularization. Incidence of graft occlusion was 3.24% (2.25-4.23), whereas
      2.13% (1.28-2.98: all CI 95%) of patients experienced stent thrombosis.
      CONCLUSION: Surgical revascularization reduces risk of revascularization for
      ULMCA patients, especially for those with Syntax score greater than 22, with a
      higher risk of in-hospital death. Intra-coronary imaging and use of arterial
      grafts improved performance of revascularization strategies.

PMID- 30095586
TI  - The Role of the Professional Supervisor in the Audiometric Testing Component of
      Hearing Conservation Programs.
AB  - : ACOEM believes that the functions of a professional supervisor in hearing
      conservation programs are part of the "core practice" of occupational medicine.
      This guidance emphasizes the role occupational medicine clinicians play in the
      supervision of audiometric surveillance conducted under the auspices of hearing
      conservation programs and reviews the regulatory and scientific basis and
      pertinent practices involved in this supervisory role.

PMID- 30095587
TI  - Occupational Noise-Induced Hearing Loss.
AB  - : Occupational hearing loss is preventable through a hierarchy of controls, which
      prioritize the use of engineering controls over administrative controls and
      personal protective equipment. The occupational and environmental medicine (OEM)
      physician plays a critical role in the prevention of occupational noise-induced
      hearing loss (NIHL). This position statement clarifies current best practices in
      the diagnosis of occupational NIHL.

PMID- 30095588
TI  - Association of Job Satisfaction and Security With Subjective Health and Well
      Being in Korean Employees.
AB  - OBJECTIVES: We evaluated an association of workplace exposure to physical factors
      (physical, chemical, and ergonomic hazards) and psychosocial factors, and of job
      satisfaction and job security with the subjective health and well-being of Korean
      workers. METHODS: This was a secondary analysis of data from the fourth Korean
      Working Conditions Survey of 2014. RESULTS: Exposure to physical factors
      (especially ergonomic factors) and psychosocial factors were negatively
      associated with good subjective health and well-being. After adjustment for
      confounding by physical factors and psychosocial factors, job satisfaction and
      job security were positively associated with good subjective health and well
      being. CONCLUSION: Korean workers with high job satisfaction and job security are
      more likely to have good subjective health and well-being, even when they are
      exposed to physical and psychosocial workplace factors. However, job satisfaction
      cannot be treated as a proxy for good working conditions.

PMID- 30095589
TI  - Association Between Workplace Social Capital and Absolute Presenteeism: A
      Multilevel Study in a Chinese Context.
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      workplace social capital (WSC) and presenteeism in a Chinese context. METHODS: We
      conducted a cross-sectional study in Shanghai, China, from December 2016 to March
      2017. Totally, 2380 workers were randomly sampled through a two-stage sampling
      procedure. Validated and psychometrically tested measures were used to assess job
      stress, self-rated health and absolute presenteeism (AP), and WSC. RESULTS: Job
      stress [unstandardized coefficients, B:1.83, 95% confidence interval (95% CI):
      0.43 to 3.24] was positively associated with AP. Compared with participants with
      excellent self-rated health, those with very good, good, and general self-rated
      health had gradationally higher levels of AP. High individual-level WSC (B: 
      6.32; 95% CI: -7.62 to -5.02) and workplace-level WSC (B: -4.43; 95% CI: -7.44 to
      -1.42) were negatively associated with AP. CONCLUSION: Interventions on promoting
      workers' health, decreasing job stress, and enhancing WSC may contribute to
      decreasing AP in Chinese workplaces.

PMID- 30095590
TI  - Medical Claims According to Wellness Program Participation for a Large Insurance
      Company in the United States.
AB  - OBJECTIVE: The aim of this study was to identify the number and total cost of
      medical claims for members of the Municipalities, Colleges, Schools Insurance
      Group by participation status in a comprehensive incentive-based wellness
      program. METHODS: Analyses are based on 6810 members during 2013 to 2016. The
      wellness program began in 2014. RESULTS: Approximately 32.5% women and 22.9% men
      (P < 0.0001) participated in the wellness program. In 2013, those who
      participated in 2014 to 2016 filed a higher number of medical claims (P =
      0.0004), but their total cost of claims was similar to those who did not
      participate in 2014 to 2016. By 2016, participants in the wellness program on
      average filed 3.6 (P = 0.0102) fewer claims and experienced $1346 (P = 0.0011)
      lower total cost of claims. CONCLUSION: Wellness program participation was
      associated with a lower number and total cost of medical claims.

PMID- 30095591
TI  - What Do Workers Do to Reduce Their Sitting Time? The Relationships of Strategy
      Use and Workplace Support With Desk-Based Workers' Behavior Changes in a
      Workplace-Delivered Sitting-Reduction and Activity-Promoting Intervention.
AB  - OBJECTIVE: To explore workers' sitting-reduction and activity-promoting strategy
      use following an intervention targeting these changes, and whether strategy use
      and perceived workplace support impacted on 3-month sitting and activity
      outcomes. METHODS: This secondary analysis in desk-based workers (n = 83)
      utilized data collected on questionnaire-derived strategy use and workplace
      support, and activPAL3-derived sitting (total; prolonged, >=30 minutes) and
      activity (standing; stepping) at work. RESULTS: Fourteen strategies were commonly
      used during the intervention. Increased usage of some strategies were
      significantly (P < 0.05) associated with beneficial changes in prolonged sitting
      or stepping only. Workplace support was significantly beneficially associated
      with changes in sitting, prolonged sitting, and stepping; these associations were
      largely independent of strategy use changes. CONCLUSIONS: Strategies were highly
      used, with increased use associated with some behavioral improvements. Workplace
      support appears essential for improving sitting and activity in the workplace.

PMID- 30095592
TI  - Volunteer and Career French Firefighters With High Cardiovascular Risk:
      Epidemiology and Exercise Tests.
AB  - OBJECTIVE: We aim to identify cardiovascular risk factors in firefighters of
      Loire (French district) with a high cardiovascular risk and report results of a
      screening program using exercise tests. METHODS: A retrospective descriptive
      study was performed in a cohort of 158 career and 400 volunteer firefighters with
      a high cardiovascular risk who had undergone an exercise test. RESULTS: Five
      hundred fifty-eight exercise tests and cardiovascular profiles were analyzed.
      Prevalence was 18% for high blood pressure, 19% for dyslipidemia, and 48% for
      overweight. Exercise tests were positive in 91 cases (16.3%): sensitivity, 53%;
      specificity, 74%. Risk of onset of a predictive event was higher in the high-risk
      group: odds ratio, 3.2 (95% confidence interval 2.0 to 5.1). There were more
      events on exercise test in volunteer firefighters. CONCLUSION: Prevalence of
      cardiovascular risk factors in the cohort of firefighters was acceptable in
      comparison to French general population and other firefighters' cohort. Physical
      training of volunteer firefighters needs reinforcing.

PMID- 30095594
TI  - Lead Pellet Ingestion in 3 Children: Another Source for Lead Toxicity.
AB  - Acute ingestions of spherical lead ammunition foreign bodies such as bullets and
      lead shot can cause acute blood lead level elevations and clinical symptoms
      necessitating emergency department evaluations and sometimes treatment. This
      article presents 3 cases of children ingesting lead ammunition, all receiving
      gastrointestinal (GI) decontamination and chelation therapy for significantly
      elevated blood lead level. Case-specific exposures and treatments for the lead
      ammunitions are presented. Radiographs documented lead pellet ingestion in all 3
      cases. Pediatric patients absorb lead from the GI tract more quickly than adults
      and may necessitate more urgent evaluation and treatment than adolescents/adults.
      More rapid GI absorption has the potential to result in possible irreversible
      neurotoxicity and neurocognitive deficits as well as behavioral changes. Failure
      of lead foreign bodies to pass from the GI tract may require more aggressive
      interventions for their removal to prevent ongoing absorption. Emergency health
      care providers should be aware of alternative lead sources besides the most
      common source of paint, as these lead foreign bodies also need urgent evaluation
      and possibly treatment.

PMID- 30095593
TI  - Sun Safe Workplaces: Effect of an Occupational Skin Cancer Prevention Program on
      Employee Sun Safety Practices.
AB  - OBJECTIVE: Occupational skin cancer prevention is a priority because outdoor
      workers are exposed to high levels of ultraviolet radiation, the primary risk
      factor for skin cancer. METHODS: A 2-year follow-up assessment of the impact of
      Sun Safe Workplaces (SSW), a workplace sun safety program that promoted policy
      adoption and education, on employee sun safety behavior was conducted. Sixty
      three of 98 local government organizations from the original study participated.
      RESULTS: Outdoor workers (n = 1724) completed surveys on personal sun protection
      practices. Employees' sun protection improved statistically significantly in the
      intervention group receiving the SSW program. SSW's effect was mediated by the
      number of workplace actions to implement elements of the policy, including sun
      protection messages and equipment and employee reports of sun safety training.
      CONCLUSION: Policy promotion is a feasible approach to occupational skin cancer
      prevention.

PMID- 30095595
TI  - Belly Dancer Syndrome: An Unusual Cause of Abdominal Pain.
AB  - BACKGROUND: Belly dancer syndrome is a rare condition consisting of involuntary,
      repetitive, often rhythmic contractions of the diaphragm, causing undulating
      movements of the abdomen that recall those of a belly dancer. It is frequently
      associated with pain or discomfort in the upper abdomen or lower chest, but
      clinical symptoms are highly variable often resulting in late diagnosis. Very few
      pediatric cases have been reported, all of which were secondary to other
      conditions, and to our knowledge, no idiopathic cases of Belly Dancer Syndrome
      have been reported in children. CASE: We present the case of a 14-year-old girl
      who presented to the emergency department with sudden onset of abdominal pain.
      She was initially diagnosed and treated for pancreatitis because blood tests
      revealed very high lipase, but when jerky abdominal wall movements became
      pronounced, belly dancer syndrome was suspected. Full work-up included abdominal
      ultrasound, chest x-ray, electroencephalogram, electromyography, magnetic
      resonance imaging, and toxic screen, all of which were normal. She was treated
      successfully with oral diazepam and referred to a pediatric neuropsychiatrist.
      CONCLUSIONS: Belly dancer syndrome is a rare condition often misdiagnosed owing
      to multiple presentations. Increased awareness is necessary to prevent late
      diagnosis and incorrect treatment.

PMID- 30095596
TI  - Providers' Ability to Identify Sentinel Injuries Concerning for Physical Abuse in
      Infants.
AB  - OBJECTIVES: The objectives of this study were to assess the ability of pediatric
      health care providers and social workers to recognize sentinel injuries in
      infants under 6 months of age and to determine what factors influence their
      decision to evaluate for physical abuse. METHODS: A statewide collaborative
      focused on sentinel injuries administered a survey to pediatric health care
      providers and social workers in the emergency department, urgent care, and
      primary care. The survey contained 8 case scenarios of infants under 6 months of
      age with an injury, and respondents were asked if they would consider the injury
      to be a sentinel injury requiring a physical abuse evaluation. Respondents were
      then presented with several factors and asked how much each influences the
      decision to perform a physical abuse evaluation. RESULTS: A total of 565
      providers completed the survey. Providers had moderate interrater reliability on
      their classification of the cases as sentinel injuries or not (kappa = 0.57).
      Nearly all respondents (97%) recognized genital bruising as a sentinel injury,
      whereas 77% of respondents recognized intraoral injuries. Agreement was highest
      among social workers (kappa = 0.76) and physicians with categorical pediatrics
      training and pediatric emergency medicine fellowship (kappa = 0.63) and lowest
      among nurse practitioners (kappa = 0.48) and residents (kappa = 0.51). Concern
      over missing the diagnosis of abuse had the greatest influence on the decision to
      perform a physical abuse evaluation. CONCLUSIONS: Sentinel injuries are not
      uniformly recognized as potential signs of child abuse requiring further
      evaluation by pediatric health care providers. Additional evidence and education
      are needed regarding sentinel injuries.

PMID- 30095597
TI  - SURGICAL MANAGEMENT OF FULL-THICKNESS MACULAR HOLE SUPERIMPOSED ON EXUDATIVE AGE
      RELATED MACULAR DEGENERATION.
AB  - BACKGROUND/PURPOSE: We describe a case of full-thickness macular hole formation
      in a patient with exudative age-related macular degeneration after an
      intravitreal ranibizumab injection and its surgical management. METHODS: This
      case is a retrospective, interventional case report. RESULTS: A 77-year-old woman
      with bilateral exudative age-related macular degeneration and pre-existing
      retinal pigment epithelium tear developed a full-thickness macular hole after
      intravitreal ranibizumab. The macular hole was repaired successfully with pars
      plana vitrectomy, internal limiting membrane peel, and 16% C3F8 gas fill.
      CONCLUSION: To the best of our knowledge, this is the first reported case of full
      thickness macular hole after a retinal pigment epithelium tear repaired
      successfully with vitrectomy, resulting in improved visual acuity.

PMID- 30095599
TI  - Protein Kinase C-Delta (PKCdelta) Tyrosine Phosphorylation is a Critical
      Regulator of Neutrophil-Endothelial Cell Interaction in Inflammation.
AB  - BACKGROUND: Neutrophil dysfunction plays an important role in inflammation
      induced tissue injury. Previously, we identified Protein Kinase C-delta
      (PKCdelta) as a critical controller of neutrophil activation and trafficking but
      how PKCdelta is regulated in inflammation hasn't been delineated. PKCdelta
      activity is regulated by tyrosine phosphorylation on multiple sites. Tyrosine155
      is a key regulator of apoptosis and gene expression, but its role in
      proinflammatory signaling is not known. METHODS: In vitro studies: superoxide
      anion (O2) and neutrophil extracellular traps (NETs) were measured in bone marrow
      neutrophils (BMN) isolated from wild type (WT) and PKCdeltaY155F knock-in mice
      (PKCdelta tyrosine 155 ->phenylalanine). Our novel 3D biomimetic microfluidic
      assay (bMFA) was used to delineate PKCdelta-mediated regulation of individual
      steps in neutrophil adhesion and migration using WT and PKCdeltaY155F BMN and
      lung microvascular endothelial cells (MLMVEC). In vivo studies: WT and
      PKCdeltaY155F knock-in mice underwent sham or cecal ligation and puncture (CLP)
      surgery and the lungs harvested 24 hrs post-surgery. RESULTS: In vitro:
      PKCdeltaY155F BMN had significantly reduced O2 and NETS release compared to WT.
      WT BMN, but not PKCdeltaY155F BMN, demonstrated significant adhesion and
      migration across TNF-activated MLMVEC in bMFA. PKCdelta inhibition significantly
      reduced WT BMN adhesion and migration under low shear and near bifurcations, but
      had no effect on PKCdeltaY155F BMN. In vivo: mutation of PKCdelta tyrosine 155
      significantly decreased neutrophil migration into the lungs of septic mice.
      CONCLUSIONS: PKCdelta tyrosine 155 is a key phosphorylation site controlling
      proinflammatory signaling and neutrophil-endothelial cell interactions. These
      studies provide mechanistic insights into PKCdelta regulation during
      inflammation.

PMID- 30095600
TI  - Neurokinin-1 Receptor Deficiency Improves Survival in Murine Polymicrobial Sepsis
      Through Multiple Mechanisms in Aged Mice.
AB  - OBJECTIVE: Substance P is a neuropeptide that contributes to a pro-inflammatory
      state by binding to the neurokinin 1 receptor (NK-1R). Limiting this interaction
      has been shown to attenuate of acute inflammation. Our hypothesis was that NK-1R
      activation would contribute to the morbidity and mortality of sepsis in a model
      using mice genetically deficient in the NK-1R. METHODS: To investigate the role
      of the SP/NK-1R axis in a murine model of sepsis, cecal ligation and puncture
      (CLP) in NK-1R deficient and wild type (WT) aged mice was performed. Acute
      inflammation was assessed by measuring circulating cytokines and clinical
      parameters. RESULTS: Deletion of the NK-1R results in improved in survival
      following CLP (NK-1R knock out mice = 100% vs wild type = 14%). A reduction in
      the inflammatory cytokines IL-6, MIP-2, and IL-1RA, improved hemodynamic
      parameters and increased neutrophilia were present in the NK-1R deficient mice
      after CLP compared to WT mice. CONCLUSIONS: These data confirm the hypothesis
      that eliminating the SP/NK-1R interaction in a highly lethal murine model of
      sepsis leads to decreased morbidity and mortality through multiple mechanisms.

PMID- 30095598
TI  - Molecular profiling of Spitz nevi identified by digital RNA counting.
AB  - The molecular properties of benign melanocytic lesions are poorly understood.
      Only a few studies have been carried out on specific nevi subtypes, including
      common nevocellular nevi (NCN) or Spitz nevi (SN). Genomic alterations in
      melanoma-associated oncogenes are typically absent in SN. In the present study,
      mRNA expressions of 25 SN and 15 NCN were analyzed. Molecular profiling was
      performed using the RNA NanoString nCounter Gene Expression Platform (number of
      genes=770). Marker discovery was performed with a training set consisting of
      seven SN and seven NCN samples from the same patients, and validation was
      performed using a second set consisting of 18 SN and eight NCN samples. Using the
      training set, 197 differentially expressed genes were identified in SN versus
      NCN. Of these, 74 genes were validated in the validation set (false discovery
      rate q<=0.13). In addition, using random forest and least absolute shrinkage and
      selection operator feature selection, a molecular signature of SN versus NCN was
      identified including 15 top-ranked genes. The present study identified a distinct
      molecular expression profile in SN compared with NCN, even when lesions were
      obtained from the same patients. Gene set analysis showed upregulation of gene
      pathways with increased expression of transcripts related to immunomodulatory,
      inflammatory, and extracellular matrix interactions as well as angiogenesis
      associated processes in SN. These findings strongly indicate that SN represent a
      distinct group of melanocytic neoplasms and evolve differentially and not
      sequentially from NCN.

PMID- 30095601
TI  - The Glaucoma Italian Pediatric Study (GIPSy): 3-Year Results.
AB  - PURPOSE: To investigate the efficacy and safety of a treatment strategy with
      latanoprost and dorzolamide in primary pediatric glaucoma patients partially
      responsive to surgery. PATIENTS AND METHODS: Children with primary pediatric
      glaucoma with postsurgical intraocular pressure (IOP) between 22 and 26 mm Hg
      were eligible. At baseline, patients were administered latanoprost once daily.
      Depending on IOP reduction, patients were allocated to continuation of
      latanoprost monotherapy or addition of dorzolamide twice daily, or switch to
      dorzolamide monotherapy 3 times daily. Patients in the dorzolamide monotherapy
      group with IOP reduction <20% from baseline were considered nonresponders. The
      primary endpoint was the percentage of responders. Study treatment continued for
      3 years or until treatment failure. RESULTS: A total of 37 patients (61 eyes)
      were analyzed. The mean age of the patients was 4.1 years (SD: 3.8). In total, 43
      eyes were included in the efficacy analysis. A total of 33 eyes (76.7%; 95%
      confidence interval, 61.4-88.2) were considered responders: 19 on latanoprost
      monotherapy, 11 on the latanoprost/dorzolamide combination, and only 3 on the
      dorzolamide monotherapy. The efficacy of pharmacological treatment was inversely
      related to central corneal thickness at the time of surgery and the age at the
      time of surgery. IOP reduction was 9.7 mm Hg (SD: 2.6) for latanoprost, 8.4 mm Hg
      (SD: 1.5) for the latanoprost/dorzolamide combination, and 9.3 mm Hg (SD: 2.5)
      for the dorzolamide monotherapy. None of the patients was withdrawn because of
      adverse events. CONCLUSIONS: Latanoprost alone or in combination with dorzolamide
      is safe and highly effective in lowering IOP in children after surgery.
      Nonresponders were mainly patients with early presentation of the disease.

PMID- 30095602
TI  - Efficacy and Safety of the Ab-interno Xen Gel Stent After Failed Trabeculectomy.
AB  - AIMS: To assess the efficacy and safety of the Xen gel stent in reducing
      intraocular pressure (IOP) in eyes with prior failed trabeculectomy and to
      determine the frequency of complications and further intervention. METHODS:
      Retrospective case note review of all patients with prior trabeculectomy
      undergoing Xen surgery across 5 centers from August 2015 to May 2017. RESULTS: In
      total, 17 surgeries were reviewed. IOP reduced from 21.5 (+/-2.4) mm Hg
      preoperatively to 13.6 (+/-3.4) mm Hg at month 12 (P<0.05). Medication usage
      reduced from 2.8 (+/-0.6) preoperatively to 1.0 (+/-1.3) at month 12 (P<0.05).
      Adverse events included: numerical hypotony (IOP<6 mm Hg) in 4 cases (23.5%) that
      all resolved spontaneously, IOP spike of >=30 mm Hg in 2 (11.8%) cases and
      transient occlusion of the implant by iris in 1 (5.9%) case. Secondary filtration
      surgery (Baerveldt tube implantation) was required in 2 (11.8%) cases.
      Postoperative bleb intervention was required in 9 cases (52.9%), usually in the
      first month after surgery. CONCLUSIONS: Xen reduces IOP and number of medications
      in eyes with failed trabeculectomy. Detailed preoperative conjunctival assessment
      and targeted stent placement is required. Prospective data and follow-up beyond
      12 months are required but Xen seems a viable, effective, and safe option after
      failed trabeculectomy.

PMID- 30095603
TI  - Prospective Evaluation of XEN Gel Implant in Eyes With Pseudoexfoliative
      Glaucoma.
AB  - PURPOSE: The main purpose of this study was to compare the safety and efficacy of
      XEN gel implant surgery in patients with pseudoexfoliative glaucoma (PEXG) and
      primary open-angle glaucoma (POAG). SETTING: This was a prospective,
      interventional study in a tertiary glaucoma center. METHODS: Fifty-seven eyes (43
      patients) with POAG and 53 eyes (42 patients) with PEXG with uncontrolled
      intraocular pressure (IOP) despite medical treatment underwent combined
      XEN+cataract surgery or standalone XEN surgery. Mean IOP, mean number of
      medications at 1-year follow-up, needling rates, and incidence of adverse effects
      (AEs) were analyzed. Complete success, defined as an IOP <16 mm Hg without
      medications at 1 year, was also analyzed. RESULTS: Combined XEN+cataract surgery
      was performed in 72% of POAG and 75% of PEXG eyes (P=0.674), the remainder
      underwent standalone XEN surgery. Patient characteristics were similar between
      the 2 groups except for higher age for the PEXG patients (78.5+/-8.5 vs. 71.3+/-
      8.7 y; P<0.001). Mean medicated IOP was 19.8+/-5.8 (POAG) and 19.7+/-8.2 (PEXG)
      at baseline (P=0.98) and 13.9+/-4.6 (-29.8%) and 13.6+/-4.3 mm Hg (-31%) at 1
      year (P=0.87), respectively (P<0.01). Mean medications dropped from 1.9+/-1.6
      (POAG) and 2.0+/-1.3 (PEXG) preoperatively to 0.4+/-0.8 and 0.5+/-0.8,
      respectively at 1 year (P<0.001). A total of 42% (POAG) and 63% (PEXG) eyes
      achieved complete success (P=0.06) at 1 year. Needling was performed in 36.8%
      (POAG) versus 37.7% (PEXG) (P=0.923). CONCLUSIONS: The XEN gel implant as a
      standalone or combined procedure demonstrated similar efficacy and safety results
      in PEXG and POAG eyes.

PMID- 30095605
TI  - Trabeculectomy With Mitomycin-C: Outcomes and Risk Factors for Failure in Primary
      Angle-closure Glaucoma.

PMID- 30095604
TI  - Fluorescein Aqueous Angiography in Live Normal Human Eyes.
AB  - PURPOSE: To evaluate aqueous humor outflow (AHO) in intact eyes of live human
      subjects during cataract surgery using fluorescein aqueous angiography. METHODS:
      Aqueous angiography was performed in 8 live human subjects (56 to 86 y old; 2 men
      and 6 women). After anesthesia, fluorescein (2%) was introduced into the eye
      [either alone or after indocyanine green (ICG; 0.4%)] from a sterile, gravity
      driven constant-pressure reservoir. Aqueous angiographic images were obtained
      with a Spectralis HRA+OCT and FLEX module (Heidelberg Engineering). Using the
      same device, anterior-segment optical coherence tomography (OCT) and infrared
      images were also concurrently taken with aqueous angiography. RESULTS:
      Fluorescein aqueous angiography in the live human eye showed segmental AHO
      patterns. Initial angiographic signal was seen on average by 14.0+/-3.0 seconds
      (mean+/-SE). Using multimodal imaging, angiographically positive signal
      colocalized with episcleral veins (infrared imaging) and intrascleral lumens
      (anterior-segment OCT). Sequential aqueous angiography with ICG followed by
      fluorescein showed similar segmental angiographic patterns. DISCUSSION:
      Fluorescein aqueous angiography in live humans was similar to that reported in
      nonhuman primates and to ICG aqueous angiography in live humans. As segmental
      patterns with sequential angiography using ICG followed by fluorescein were
      similar, these tracers can now be used sequentially, before and after trabecular
      outflow interventions, to assess their effects on AHO in live human subjects.

PMID- 30095606
TI  - Achondroplasia With Congenital Onset Glaucoma, and Presumed Axenfeld-Rieger
      Anomaly.
AB  - We report the first case to our knowledge of a 1-week-old female infant with
      familial inherited achondroplasia associated with bilateral congenital onset
      glaucoma, posterior embryotoxon and iris hypoplasia suggestive of ocular Axenfeld
      Rieger anomaly.

PMID- 30095607
TI  - Inner Retinal Changes in Primary Open-Angle Glaucoma Revealed Through Adaptive
      Optics-Optical Coherence Tomography.
AB  - PURPOSE: To examine the microstructural changes in the inner nuclear layer (INL)
      and ganglion cell layer (GCL) in a primary open-angle glaucoma (POAG) subject at
      2 timepoints, 4 months apart. PATIENTS AND METHODS: This case-control study (1
      POAG subject and 1 normal control) used the single cell, 3-dimensional volumetric
      imaging capability of an adaptive optics-optical coherence tomography-scanning
      laser ophthalmoscopy system to examine the inner retina. RESULTS: At the area of
      greatest glaucomatous change in the POAG subject [3-degrees temporal (T), 3
      degrees inferior (I), right eye], the GCL was greatly thinned at both timepoints,
      yet retinal ganglion cell soma remained visible amid a meshwork of capillaries.
      Microcystic lesions in the INL were visible at both timepoints, ranging in
      diameter from 8 to 43 MUm on day 1 to 11 to 64 MUm at 4 months, with an average
      diameter increase of ~124%. Small hyperreflective features (not seen in the
      contralateral eye or control subject) at a depth midway through the INL seemed
      correlated to the development of microcysts. CONCLUSIONS: We demonstrate the
      ability to image microcystic lesions early in their development and have
      quantified longitudinal changes. The presence of small hyperreflective structures
      at a layer midway through the INL seems to be a precursor to their formation and
      is a potential biomarker for assessing POAG severity and progression. The
      adaptive optics imaging system is also able to visualize retinal ganglion cells
      in this subject, despite severe thinning of the GCL.

PMID- 30095609
TI  - World Gastroenterology Organisation (WGO) News and Events.

PMID- 30095608
TI  - Preoperative Brimonidine Tartrate 0.2% Does not Prevent an Intraocular Pressure
      Rise During Prostatectomy in Steep Trendelenburg Position.
AB  - PURPOSE: This study evaluated the effect of preoperative brimonidine tartrate
      0.2% on intraocular pressure (IOP) during robotic-assisted laparoscopic radical
      prostatectomy in steep Trendelenburg position (sTBURG). MATERIALS AND METHODS: In
      this prospective randomized controlled masked interventional trial, eligible
      patients scheduled for robotic-assisted laparoscopic radical prostatectomy in
      sTBURG at the Toronto General Hospital had one eye randomized to placebo
      (artificial tears) or drug (brimonidine tartrate 0.2%) preoperatively. Visual
      acuity (VA), tonometry, disc photography, visual field (VF), and retinal nerve
      fiber layer (RNFL) assessments were performed preoperatively and postoperatively.
      A standardized anesthetic protocol was followed intraoperatively. IOP was
      measured using Tono-Pen AVIA (Reichert Inc., New York, NY) as follows:
      preanesthesia supine, anesthetized supine, hourly in sTBURG and awake supine. The
      primary outcome was IOP in sTBURG in the drug group compared with the placebo
      group. Secondary outcomes were changes in VA, VF, RNFL thickness, mean arterial
      pressure, and ocular perfusion pressure. This study was approved by University
      Health Network Research Ethics Board. RESULTS: In total, 26 eligible patients,
      mean age 61.9+/-5.1 years, were randomized to brimonidine (11 patients) and
      placebo (15 patients). Baseline IOP was not significantly different between the
      drug and placebo groups (P=0.42). Significant and sustained IOP elevation of
      >1.5X baseline in the sTBURG was noted in both groups. The mean IOP 1 hour after
      sTBURG was 29.4+/-6.9 and 27.2+/-3.4 mm Hg in the drug and placebo groups,
      respectively (P=0.35). No significant changes were noted in VA, VF, or RNFL.
      CONCLUSIONS: Significant and sustained IOP increases occur during sTBURG.
      Preoperative brimonidine does not prevent IOP spikes in sTBURG.

PMID- 30095610
TI  - Identification of a novel mutation of RUNX2 in a family with supernumerary teeth
      and craniofacial dysplasia by whole-exome sequencing: A case report and
      literature review.
AB  - RATIONALE: Supernumerary teeth are those that teeth in excess number than the
      normal count. It is usually associated with genetic syndromes when present in
      more numbers. Several causal genes, such as APC, NHS, TRPS1, EVC and RUNX2, have
      been identified. However, etiology of supernumerary teeth remains largely
      unclear. PATIENT CONCERNS: A family with the clinical diagnosis of supernumerary
      teeth, short stature and craniofacial dysplasia was examined. DIAGNOSES:
      Molecular genetic analysis found that mutation occurred in the RUNX2 gene. On the
      basis of this finding and clinical manifestations, the final diagnosis of
      cleidocranial dysplasia was made. INTERVENTIONS: Whole exome sequencing (WES) of
      DNA samples was performed to identify the disease-causing mutation, including the
      affected child and mother as well as the healthy father. OUTCOMES: A novel
      mutation of RUNX2 (c.473C>A; p.A158E) was identified in both patients, but not in
      normal family member and in-house database containing 3,000 Chinese Han
      individuals WES. This mutation was further confirmed by Sanger sequencing and
      predicted to be deleterious by several commonly used algorithms, including SIFT,
      PPT-2, MutationTaster and Proven. Furthermore, phenotype-genotype correlation
      analyses of all published 239 cases with different mutations in RUNX2 revealed
      significant association of supernumerary teeth and facial dysplasia with the Runt
      domain of the encoded protein. LESSONS: This is the first WES study to identify
      genetic cause in Chinese patients with a novel RUNX2 mutation. Our findings
      expanded the mutation spectrum and clinical features of the disease and
      facilitated clinic diagnosis and genetic counseling.

PMID- 30095611
TI  - Adding value to myocardial perfusion SPECT/CT studies that include coronary
      calcium CT: Detection of incidental pulmonary arterial dilatation.
AB  - The aim of the present study was to evaluate the incidence of undiagnosed
      pulmonary arterial dilatation using the gated computed tomography (CT) images
      acquired in patients with an otherwise normal Tc-sestamibi single-photon-emission
      CT (SPECT)/CT myocardial perfusion study.This was a retrospective review of 200
      consecutive patients (100 men, mean age 58.7 years) who underwent a myocardial
      perfusion Tc-sestamibi SPECT/CT study with normal perfusion and with gated CT
      images acquired for coronary calcium scoring. The CT images were reviewed using a
      previously validated mean main pulmonary artery diameter (mPAD) measurement
      method which has been correlated with pulmonary arterial hypertension (PAH).
      Clinical information on multiple comorbidities was also retrieved. Previously
      reported mPAD cutoffs (>29.5 and >31.5 mm) were used to stratify
      patients.Indications for the study included dyspnea on exertion (58.9%),
      preoperative workup (22.3%), and chest pain (13.9%). The mean mPAD measurement
      was 26.3 mm (+/-0.5). There was a significant correlation between body mass index
      and mPAD (correlation coefficient [rho]: 0.28; P < .001). About 23% (46/200) of
      patients had mPAD > 29.5 mm and 15.0% (30/200) of patients had mPAD > 31.5 mm.
      From previous work, these cutoffs have a sensitivity and specificity for PAH of
      70.8%, 79.4% and 52.0%, 90.2%, respectively. Among patients undergoing a
      preoperative myocardial perfusion study, 35.6% (16/45) patients had mPAD > 29.5
      mm and 26.7% (12/45) patients had mPAD > 31.5 mm. There was a higher prevalence
      of congestive heart failure (62.5% vs 19.6%; P < .001) and hypertension (78.3% vs
      21.7%; P < .02) in patients with mPAD > 29.5 mm. Similarly, there was a high
      prevalence of congestive heart failure (P < .001), hyperlipidemia (P < .04), and
      hypertension (P < .04) in patients with mPAD > 31.5 mm.Incidental pulmonary
      arterial dilatation (mPAD >= 29.5 mm) can be detected in a large number of
      patients with normal myocardial perfusion scintigraphy and correlates with
      multiple different comorbidities. The mPAD can be measured in all patients
      undergoing gated imaging as part of a myocardial perfusion study, and PAH may be
      considered as an alternative explanation for symptoms in some patients without
      perfusion deficits. The data to make this potential diagnosis is already being
      acquired and represents an opportunity to add value to the interpretations of
      otherwise negative myocardial perfusion studies.

PMID- 30095612
TI  - Pooled analysis of the comparative efficacy between tacrolimus and infliximab for
      ulcerative colitis.
AB  - BACKGROUND: Acute moderate-to-severe steroid-refractory ulcerative colitis (UC)
      has a poor prognosis and requires optimal rescue therapy. A pooled analysis was
      conducted to assess tacrolimus and infliximab (IFX) as rescue agents in patients
      with moderate-to-severe and steroid-refractory UC. METHODS: A literature search
      identified studies that investigated tacrolimus and IFX in moderate-to-severe
      steroid-refractory patients with UC. The primary outcome was short-term clinical
      response to treatment, including the remission and response rates. Secondary
      outcomes included the rates of colectomy at 3 months and adverse events rate.
      RESULTS: A total of 6 studies comprising 438 cases were eligible for inclusion.
      The pooled analysis showed that the short-term clinical response rate, clinical
      remission rate, and 3-month colectomy rate were 72.1%, 52.4%, and 10.1%,
      respectively, for those receiving tacrolimus, and 76.9%, 48.8%, and 12.4%,
      respectively, for those receiving IFX. No significant difference was, however,
      seen for tacrolimus compared with IFX with regard to clinical remission rate
      (odds ratio [OR] =1.08, 95% confidence interval [CI] = 0.77-1.49, P = .67),
      clinical response rate (OR = 0.92, 95% CI = 0.63-1.34, P = .66), and 3-month
      colectomy rate (OR = 0.86, 95% CI = 0.39-1.93, P = .72). More adverse events
      were, however, observed in the Tac group (OR = 2.16, 95% CI = 1.25-3.76, P =
      .006). CONCLUSIONS: Our meta-analysis suggested that both tacrolimus and IFX
      appeared to be effective and safe for the rescue therapy of moderate-to-severe
      active UC and steroid-refractory UC. Therefore, tacrolimus is another choice for
      these patients.

PMID- 30095614
TI  - Incidental bone metastases identified by renal dynamic scintigraphy: A case
      report.
AB  - INTRODUCTION: The Technetium-99m diethylene triamine pentaacetic acid (Tc-99m
      DTPA) renal dynamic scintigraphy is widely used to evaluate the split renal
      function and continuously demonstrate the whole urinary collecting system.
      Furthermore, the extrarenal uptake of technetium-99m DTPA can provide useful
      information for the patients. CASE PRESENTATION: We described a 72-year-old male
      with a history of flank pain for 8 months and gross hematuria for 3 days. The
      technetium-99m diethylenetriaminepenta-acetic acid (DTPA) renal dynamic
      scintigraphy was performed to evaluate the split renal function. Unexpectedly,
      there were 2 foci of abnormal increased tracer uptake in the midline of the
      abdomen. The diagnosis of renal cancer was made on the basis of the imaging
      characteristics on the ultrasonography. The 2 foci with elevated DTPA activity
      were consistent with bone metastases on the images of computed tomography and
      magnetic resonance. CONCLUSION: The bone metastasis is one of the etiologies of
      the extrarenal uptake of technetium-99m DTPA, especially for the patients with
      several foci.

PMID- 30095613
TI  - Altered long noncoding RNAs and survival outcomes in ovarian cancer: A systematic
      review and meta-analysis (PRISMA Compliant).
AB  - BACKGROUND: Previous studies investigating the association between altered long
      noncoding RNAs (lncRNAs) and survival outcomes in ovarian cancer have obtained
      controversial results. To comprehensively evaluate the association, we conducted
      a systematic review and meta-analysis of the studies published on the subject.
      METHODS: We performed a systematic search using the databases of the Cochrane
      Central Register of Controlled Trials, PubMed, and Embase to find all relevant
      articles from inception to May 7, 2017. Studies that evaluated the association
      between 1 specific lncRNA and survival outcomes in ovarian cancer were included.
      Pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) for overall
      survival, progression-free survival, and disease-free survival were calculated
      with a fixed-effects or random-effects model. RESULTS: A total of 15 studies
      involving 1333 patients with ovarian cancer were included in this meta-analysis.
      Altered lncRNAs were associated with decreased overall survival (HR: 2.29, 95%
      CI: 1.92-2.75) without heterogeneity (I = 0.0%) in ovarian cancer. Altered
      lncRNAs were also associated with decreased progression-free survival (HR: 2.77,
      95% CI: 1.00-7.62, I = 76.6%) and disease-free survival (HR: 2.59, 95% CI: 0.89
      7.57, I = 62.9%) in ovarian cancer. CONCLUSION: Our results supported the strong
      prognostic value of altered lncRNAs in ovarian cancer. Further large-scale
      studies should be carried out to verify the clinical applications of altered
      lncRNAs in the prognosis assessment of ovarian cancer.

PMID- 30095615
TI  - A novel CRX frameshift mutation causing cone-rod dystrophy in a Chinese family: A
      case report.
AB  - BACKGROUND: Cone-rod dystrophy (CORD) is an inherited, progressive retinal
      disorder with genetic and phenotypic heterogeneity. Here, we aimed to identify
      the pathogenic mutation in affected individuals in a Chinese family with
      autosomal dominant cone-rod dystrophy (adCORD). METHODS: Genomic DNA and clinical
      examination results were collected from a Chinese family presenting with adCORD.
      The candidate disease-causing mutations were screened with whole-exome sequencing
      (WES) and bioinformatics analyses. Sanger sequencing was used for validation and
      cosegregation analysis. RESULTS: A novel frameshift mutation (NM_000554.4;
      c.538dupG:p.Val180fs) in exon 4 of the CRX gene was identified in all affected
      individuals in the Chinese family with adCORD. Cosegregation analysis confirmed
      that this mutation was cosegregated with the disease. This variant, which results
      in premature termination of the protein, was absent from all public variant
      databases or internal exome databases. CONCLUSIONS: We used whole-exome
      sequencing to identify a novel CRX mutation causing adCORD in a Chinese family.
      This study broadens the known pathogenic mutation spectrum of the CRX gene and
      shows the potential of WES in identifying the pathogenic mutations of CORD
      disease.

PMID- 30095617
TI  - A case report of hepatopulmonary syndrome in hereditary hemorrhagic
      telangiectasia (HHT): Not all right-to-left shunting in HHT is due to pulmonary
      arteriovenous malformations.
AB  - RATIONALE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant
      disorder characterized by abnormal vessel growth that results in telangiectasias
      and arteriovenous malformations (AVMs) in the skin, mucosa, and viscera. Up to
      30% of patients with HHT exhibit pulmonary AVMs (PAVMs), clinically manifesting
      as right-to-left shunting and hypoxemia. PATIENT CONCERNS: We report an unusual
      and novel case of a patient with HHT who lacked clinical sequelae of portal
      hypertension but presented to clinic with hypoxemia without dyspnea. DIAGNOSES:
      Diagnostic workup revealed noncardiac right-to-left shunting due to
      hepatopulmonary syndrome (HPS) from HHT-induced portal hypertension rather than
      PAVMs. The diagnosis was confirmed by the absence of PAVMs on chest computed
      tomography and evidence of elevated portal pressures as noted by the presence of
      small esophageal varices on upper endoscopy and histologic findings on liver
      biopsy. INTERVENTION: Due to the patient's mild symptoms, no further intervention
      was required. He was closely followed up in the outpatient setting for changes in
      symptoms and underwent annual screening for development of PAVMs. OUTCOMES: The
      patient continues to do well clinically. He has not experienced worsening
      hypoxemia or dyspnea and has not developed PAVMs. LESSONS: Given that management
      of hypoxemia in HPS drastically differs from that of hypoxemia due to PAVMs, this
      case demonstrates the importance of evaluating HHT patients for HPS if they
      exhibit impaired oxygenation and noncardiac right-to-leftshunting in the setting
      of hepatic arteriovenous shunting.

PMID- 30095616
TI  - MicroRNA-200 and microRNA-30 family as prognostic molecular signatures in ovarian
      cancer: A meta-analysis.
AB  - BACKGROUND: MicroRNAs (miRs) play a vital role in the occurrence, development,
      and progression of human cancers, but its role in the prognosis of ovarian cancer
      is unclear. METHODS: We performed a meta-analysis by searching PubMed, Embase,
      and Web of Science databases for eligible studies. The pooled hazard ratios (HRs)
      and 95% confidence intervals (CIs) were used to explore the association between
      miRs expression and overall survival (OS) and progression-free survival (PFS) on
      ovarian cancer patients. We also used Kaplan-Meier to analyze the relationship
      between miRs and OS in OncoLnc dataset. RESULTS: A total of 15 records were
      included into the meta-analysis. The expression level of miR-200 family showed
      significant association with OS (HR = 0.78, 95% CI: 0.64-0.94) and insignificant
      association with PFS (HR = 0.72, 95% CI: 0.50-1.03). Subgroup analysis revealed
      that an increased expression level of miR-200c was associated with better OS (HR
      = 0.59, 95% CI: 0.45-0.74). An increased expression level of miR-200a, miR-200c,
      and miR-141 was associated with better PFS (miR-200a, HR = 0.59, 95% CI: 0.42
      0.75; miR-200c, HR = 0.50, 95% CI: 0.14-0.87, miR-141, HR = 0.38, 95% CI: 0.12
      0.63). Similarly, higher expression of miR-30 family was associated with elevated
      OS/PFS for ovarian cancer (OS, HR = 0.43, 95% CI: 0.13-0.74; PFS, HR = 0.76, 95%
      CI: 0.64-0.87). The OncoLnc dataset presented that elevated expression level of
      miR-30d-5p was associated with better OS (n = 470, P = .0197). CONCLUSION: The
      meta-analysis reveals that miR-200 family and miR-30 family could be promising
      prognostic biomarkers of ovarian cancer.

PMID- 30095618
TI  - Clinical, biochemical, and genetic analysis of the mitochondrial respiratory
      chain complex I deficiency.
AB  - Mitochondrial respiratory chain complex I deficiency is one of common
      mitochondrial disorders. However, the information is relatively little about the
      features of Chinese patients. In this study, the clinical, biological, and
      genetic analyses were performed in the children with respiratory chain complex I
      deficiency, in order to further understand the characteristics of the
      disease.Over a 3-year period, 67 patients (37 boys, 30 girls), presenting with
      unexplained multisystemic symptoms and signs were recruited. Clinical and
      laboratory data of the patients were summarized. Spectrophotometric assay was
      used for the analysis of mitochondrial complex I-V enzyme activity in peripheral
      leukocytes. The entire mitochondrial DNA (mtDNA) sequence was analysed for
      patients and their mothers.The children with respiratory chain complex I
      deficiency presented with multisystem dysfunction. Onset occurred before the
      third year of life in 96.9% patients without mtDNA mutation. Onset occurred
      before the third year of life in 76.5% of patients with mtDNA mutation (P = .03).
      About 51.5% of patients without mtDNA mutation had weakness, which is higher than
      24% patients with mtDNA mutation (P = .02). Isolated complex I deficiency and
      combined complex I deficiency were found in 45 and 22 patients, respectively. The
      prevalence of isolated complex I deficiency was higher in the patients with mtDNA
      mutations (79.4%) than in the patients without mtDNA mutations (54.5%).Patients
      with nuclear DNA mutations are more likely to develop early onset in
      mitochondrial respiratory chain complex I deficiency. The patients with complex I
      deficiency of peripheral leukocytes may be more likely to be caused by mtDNA
      mutation.

PMID- 30095619
TI  - Clinicopathological features of atypical membranous nephropathy with unknown
      etiology in adult Chinese patients.
AB  - Membranous nephropathy is typically classified as idiopathic and secondary, but
      nowadays the number of atypical membranous nephropathy (aMN) is increasing, many
      of which cannot determine its etiology in China. In this study, we compared the
      clinical and pathological characteristics of idiopathic membranous nephropathy
      (iMN) with aMN with unknown etiology from a single center in China.We
      retrospectively reviewed the clinical data of 577 patients with iMN and aMN at
      Peking University People's Hospital from January 2006 to December 2015 over a 10
      year period, and analyzed their clinical and pathological characteristics. The
      level of serum phospholipase A2 receptors (PLA2R) antibody was detected in 106
      iMN and 162 aMN patients.There were 278 iMN patients and 299 aMN patients who
      were included into this study in 3210 cases of renal biopsy during a 10-year
      period in our hospital. The average age of patients with iMN was significantly
      older than those with aMN (54.77 +/- 13.01 vs 47.13 +/- 16.16, P < .001). Around
      75 patients (27%) were smokers in iMN patients, and 111 patients (37.1%) in aMN
      patients (P = .009). The mainly clinical manifestation of these 2 groups was
      nephrotic syndrome (61.5% in iMN group vs 58.4% in aMN group), but there were
      more patients accompanied with nephritis syndrome in aMN group than iMN group
      (17.1% vs 6.1%, P < .001). The immunofluorescence of renal biopsy showed "full
      house" in aMN group; and IgG subclass of the glomeruli demonstrated IgG4 (90.4%)
      was commonest in iMN group, but IgG1 (94.6%) in aMN group. 51 (48.1%) patients
      with iMN were detected positive PLA2R antibody in their serum, and 93 (57.4%) in
      aMN patients (P = .168). The patients with positive PLA2R antibody had higher
      positive rate of microscopic hematuria and urinary protein, lower albumin.The aMN
      patients are younger, higher smoking rate, its main clinical manifestation is
      nephrotic syndrome, but more of them accompanied with nephritis syndrome than
      those in iMN patients. Serum PLA2R antibody could not distinguish aMN from iMN.
      aMN could be a special glomerular disease in China, and need a further research
      on a larger scale.

PMID- 30095620
TI  - Borderline tuberculoid leprosy mimicking sarcoidosis: A case report.
AB  - INTRODUCTION: Leprosy is a chronic infectious granulomas disease caused by
      Mycobacterium leprae that can manifest as a wide variety of immunological and
      clinical features. CASE SUMMARY: Here, we describe the case of a woman with
      clinical characteristics of borderline tuberculoid (BT) leprosy that manifested
      as 3 asymmetric skin lesions involving her hip and lower limbs. This unusual
      presentation was initially misdiagnosed as sarcoidosis because noncaseating
      granulomas are a histopathological feature of both diseases. Differentiation and
      the diagnosis of BT leprosy was achieved using real-time polymerase chain
      reaction (PCR) to amplify an M leprae specific DNA sequence and to detect serum
      antibodies specific to M leprae antigens. Accordingly, a 6-month course of
      multidrug therapy led to a marked improvement in the skin lesions. CONCLUSION:
      The use of auxiliary tests including real-time PCR to amplify an M leprae
      specific DNA sequence, enzyme-linked immunosorbent assay, and dipstick detection
      of serum antibodies specific to M leprae antigens are good methods to obtain a
      correct diagnosis of BT leprosy.

PMID- 30095622
TI  - The feasibility of 1-stop examination of coronary CT angiography and abdominal
      enhanced CT.
AB  - This study aims to evaluate the feasibility of performing coronary computed
      tomography angiography (CCTA) and abdominal enhanced computed tomography (CT)
      with 1-time injection of the agent.CCTA images (right coronary artery, left
      anterior descending coronary artery, and left circumflex coronary artery) were
      collected from 20 patients who completed a 1-stop combined examination of CCTA
      and abdominal enhanced CT (group A), 20 patients who only underwent abdominal
      enhanced CT (group B1), and 20 patients who only underwent CCTA (group B2). These
      images were interpreted using the 5-point Likert scale system by 2 experienced
      radiologists, and abdominal images were observed for breathing artifact. CT
      value, signal-to-noise ratio (SNR), and CTDI were recorded and compare among the
      3 groups.The difference in image quality of the coronary and total volume of the
      contrast agent between group A and group B1 was not statistical significant (P >
      .05). The CT value and SNR in group B1 (CCTA) (CT: 394.65 +/- 59.23, SNR: 17.38
      +/- 4.13) increased, compare with Group A (CT: 360.35 +/- 34.16, SNR: 13.76 +/-
      1.84, P = .03, .01), while CTDI was undifferentiated between group A (17.14 +/-
      6.20) and group B1 (18.38 +/- 9.79) (P = .64). The difference in CT value and SNR
      at the arterial phase and CT value at the venous phase between group A (abdomen)
      and group B2 were statistically significant, the CTDI in group A (9.09 +/- 1.05)
      increased, compared with group B2 (8.23 +/- 1.33) (P = .03), and SNR at the
      venous phase in group B2 (12.50 +/- 2.43) increased, compared with group A (10.89
      +/- 2.03) (P = .03).Revolution CT can capture full images and very rapidly switch
      to the scan mode, enabling a 1-stop axial CCTA and enhanced helical abdominal
      scan. The 1-stop combined scan resulted in a satisfactory image quality, which
      reduced the contrast agent dose and simplified the workflow.The 1-stop combined
      scan allows for the high success rate of the examination, reduces the number of
      examinations, and decreases the dose and risk of injection of the contrast agent.
      This would be helpful for patients to obtain diagnostic images in time.

PMID- 30095621
TI  - Correlation of quantified metabolic activity in nonsmall cell lung cancer with
      tumor size and tumor pathological characteristics.
AB  - The aim of this study was to evaluate the relationship between maximum
      standardized uptake value (SUVmax) with tumor size and tumor pathological
      characteristics as well as suggesting equations between SUVmax and tumor size in
      patients with nonsmall cell lung cancer (NSCLC) to help differentiate between
      pathology types.We retrospectively analyzed the fluorodeoxyglucose-positron
      emission tomography/computed tomography (FDG-PET/CT) findings of 98 patients with
      NSCLC. Statistical differences were considered significant when P < .05.
      Correlation between SUVmax and other variables was determined by Pearson and
      Spearman correlation. Both linear and nonlinear regression analysis were used to
      determine equations between SUVmax and tumor size to help differentiate between
      pathology types.The mean SUVmax in patients with squamous cell carcinoma was
      significantly higher than that of adenocarcinoma (21.35 +/- 1.73 vs 13.75 +/-
      0.89, P = .000). The results of regression analysis indicated that among all
      equations determined with relative accuracy, the "cubic equation" has the highest
      accuracy when considering the relationship between SUVmax and tumor size in
      patients with adenocarcinoma. In patients with squamous cell carcinoma, the most
      accurate equation was obtained using the "quadratic equation."There was a
      significant correlation between SUVmax and tumor differentiation and tumor size
      in patients with adenocarcinoma. SUVmax of patients with squamous cell carcinoma
      also had a significant correlation with tumor size. Overall SUVmax of patients
      with NSCLC could be predicted by tumor size value. In patients with squamous cell
      carcinoma compared with those with adenocarcinoma, SUVmax with less accuracy can
      be determined by tumor size. Linear regression analysis line slope can be used as
      an index for distinguishing adenocarcinoma from squamous cell carcinoma.

PMID- 30095623
TI  - Treatment of human chronic wounds with autologous extracellular matrix/stromal
      vascular fraction gel: A STROBE-compliant study.
AB  - Stem cell therapy is considered as the most promising treatment for chronic
      wounds. Extracellular matrix/stromal vascular fraction gel (ECM/SVF gel), an
      adipose-derived stem cell-based cytotherapy, has shown healing potential in
      experimental wounds in animal models. However, the effects of ECM/SVF gel on
      human chronic wounds have not been investigated. The aim of the present study is
      to investigate the therapeutic effect of ECM/SVF gel on human chronic
      wounds.Autologous ECM/SVF gel was prepared and used to treat patients with
      chronic wounds in clinics, with negative pressure wound therapy as the positive
      control. Wound healing rate per week and histological changes were performed.The
      average wound healing rate per week in the ECM/SVF gel group was 34.55 +/- 11.18%
      compared with 10.16 +/- 2.67% in the negative pressure wound therapy group (P <
      .001). Histological analysis with hematoxylin and eosin, Masson's trichrome
      staining, and CD31 immunohistochemistry showed less lymphocyte infiltration, more
      collagen accumulation, and more newly formed vessels in the ECM/SVF gel group
      treated skins compared to the control.ECM/SVF gel is an effective therapeutic
      option for chronic wound healing in clinics.

PMID- 30095624
TI  - Improved differentiation between high- and low-grade gliomas by combining dual
      energy CT analysis and perfusion CT.
AB  - The purpose of this study was to investigate the value of the cerebral blood
      volume (CBV) obtained with perfusion computed tomography (CT) and the electron
      density (ED) measured by dual-energy CT for differentiating high- from low-grade
      glioma (HGG, LGG).The CBV and ED were obtained in 9 LGG and 7 HGG patients. The
      CBV and ED of LGGs and HGGs were compared. Receiver operating characteristic
      (ROC) curves were generated for CBV, ED, and CBV plus ED. The correlation between
      CBV, ED, and the MIB-1 labeling index of the tumors was examined. All of these
      analyses were also performed using relative CBV (rCBV) and ED (rED) (the value of
      tumors/the value of contralateral white matter).The mean CBV, ED, rCBV, and rED
      values were significantly higher in HGG than LGG (P < .05). By ROC analysis, the
      combination of rCBV plus rED as well as CBV plus ED were more accurate than CBV,
      ED, rCBV, rED alone. There was a significant correlation between ED and MIB-1 (P
      = .04).ED improved diagnostic accuracy of perfusion CT for differentiating HGG
      from LGG.

PMID- 30095626
TI  - Ketamine infusion therapy for chronic pain management in South Korea: A national
      survey for pain physicians with a narrative review.
AB  - Although ketamine infusion therapy (KIT) has been used extensively for the
      treatment of chronic persistent pain, there remains high heterogeneity in the
      administration protocols. The aim of this study was to assess the current
      clinical use and the infusion protocols of KIT in South Korea and to compare the
      protocol details with previous relevant studies.In the first phase, an online
      survey about KIT, including protocol information, was distributed to pain
      physicians managing chronic pain patients at 47 teaching hospitals registered in
      the Korean Pain Society. In the second phase, a review of the KIT protocols in
      previous clinical studies was conducted and compared with the survey
      results.Among 47 institutions, 35 replied; among them, 25 institutions performed
      KIT on an outpatient basis. The administration protocol for KIT varied greatly
      among institutions: the total infusion dose of ketamine ranged from 3.5 to 140
      mg/70 kg, with a mode of 70 mg [interquartile range (IQR): 62.0; 8.0-70.0 mg]
      administered in 1 to 3 hours. In 10 previous studies of outpatient KIT, the total
      dose of ketamine ranged from 12.6 to 98 mg/70 kg, with a mode of 35 mg [IQR: 40
      mg; 23-63 mg] given in 1 to 4 hours, which was significantly lower than in our
      results (P = .01). In the survey, physicians listed hallucination as the most
      frequent side effect.Although KIT is used in Korean pain centers, there is wide
      variation regarding the specific infusion protocols. The total dose of ketamine
      used in South Korea is significantly higher than the general recommendations for
      outpatient management and may compromise patient safety. The results of this
      survey reinforce the need for specific guidelines for KIT in managing chronic
      pain that counterbalance its risks and benefits.

PMID- 30095625
TI  - Impact of right coronary dominance on triple-vessel coronary artery disease: A
      cross-sectional study.
AB  - This study was conducted to investigate the relationship between right coronary
      dominance and coronary angiographic characteristics in patients with or without
      significant coronary artery disease (CAD).A total of 2225 patients undergoing
      coronary angiography (CAG) between January 2011 and November 2014 were recruited
      in our study. Based on the CAG results, patients were divided into the left
      dominance (LD) group, right dominance (RD) group, and co-dominance (CD) group.
      Multinomial logistic regression was applied to analyze the relationships between
      coronary dominance and triple-vessel CAD.We found that patients with RD had a
      higher prevalence of triple-vessel CAD (36.6% vs 27.3%, P = .008) and significant
      stenosis in the right coronary artery (40.5% vs 29.2%, P = .001). In addition,
      results of multinomial logistic regression analysis showed that RD was
      significantly associated with the triple-vessel disease (odds ratio 1.768, 95%
      confidence interval 1.057-2.956, P = .030).In conclusion, RD positively
      correlated with triple-vessel CAD rather than LD or CD in patients. This result
      suggested that RD may serve as a risk factor for triple-vessel CAD and more
      effective measures should be taken in RD patients to prevent fatal cardiovascular
      events.

PMID- 30095627
TI  - Postpartum sacral stress fracture associated with mechanical sacroiliac joint
      disease: A case report.
AB  - RATIONALE: Stress fractures of the sacrum and mechanical sacroiliac joint disease
      can occur not only during pregnancy but also postpartum. Mechanical sacroiliac
      joint disease is common in patients with low back pain but often misdiagnosed by
      practitioners. The association of the 2 conditions has not been studied yet.
      PATIENT CONCERNS: A 37-year-old woman physiatrist presented with 8-week history
      of persistent low back and left buttock pain that started in the third trimester
      of her pregnancy. DIAGNOSES: Laboratory investigation, dual-energy x-ray
      absorptiometry, magnetic resonance imaging, and CT of the pelvic region were
      performed. The patient was diagnosed with postpartum sacral stress fracture
      associated with mechanical sacroiliac joint disease. INTERVENTIONS: Treatment
      consisted in pain killers and tailored to a nonweight-bearing period of 3 months.
      OUTCOMES: Painful symptoms disappeared and the patient was able to walk and
      perform other daily activities normally. LESSONS: Clinician should be aware of
      the clinical context and the possible association of these 2 conditions in order
      to undertake an early and appropriate treatment.

PMID- 30095628
TI  - Accelerated diffusion-weighted imaging for lymph node assessment in the pelvis
      applying simultaneous multislice acquisition: A healthy volunteer study.
AB  - To evaluate the feasibility of accelerated simultaneous multislice diffusion
      weighted sequences (SMS-DWI) for lymph node detection in the abdominopelvic
      region. Sequences were evaluated regarding the number and depiction of lymph
      nodes detected with SMS-DWI compared with conventional diffusion weighted
      sequences, the most suitable SMS- acceleration factor, signal-to-noise ratio
      (SNR), and the overall acquisition time (TA).Eight healthy volunteers (4 men, 4
      women; age range 21-39 years; median age 25 years) were examined in the pelvic
      region at 3T using a conventional DWI sequence and a SMS DWI sequence with
      different acceleration factors (AF: 2-3). Moreover, a SMS DWI sequence with AF 3
      and higher slice resolution was applied. For morphological correlation of the
      lymph nodes and as a reference standard, an isotropic 3-dimensional T2-weighted
      fast-spin-echo sequence with high sampling efficiency (SPACE) was acquired. Two
      radiologists reviewed each DWI sequence and assessed the number of lymph nodes
      and the overall image quality. For each DWI sequence, SNR, SNR efficiency per
      time, contrast to noise (CNR), and ADC values were calculated. Values were
      statistically compared using a Wilcoxon test (P < .05).Overall, scan time of SMS
      DWI with AF2 (AF3) decreased by 46.9% (57.2%) with respect to the conventional
      DWI. Compared with the SPACE sequence, the detection rate was 89.6% for
      conventional DWI, 69.4% for SMS-DWI with AF2, and 59.9% for SMS-DWI with AF3. The
      highly resolved SMS-DWI with AF3 leads to a scan time reduction of 46.9% and
      detection rate of 83.0%. SNR and CNR were lower in the accelerated sequences (up
      to 51.0%, P < .001) as compared with the conventional DWI. SNR efficiency
      decreased to 19.3% for AF2 and to 31.3% for AF3. In the highly resolved dataset,
      an SNR efficiency reduction of 51.2% was found.This study showed that lymph node
      detection in the abdominopelvic region with accelerated SMS-DWI sequences is
      feasible whereby an AF of 2 represents the best compromise between image quality,
      SNR, CNR, TA, and detection rate.

PMID- 30095629
TI  - Treatment of large fibroepithelial polyps in the proximal ureter with antegrade
      plus retrograde endoscopic laser polypectomy.
AB  - The diagnosis and treatment of large fibroepithelial polyps in the proximal
      ureter have been the clinical challenges. This study retrospectively summarized
      the clinical diagnosis and treatment of fibroepithelial polyps >5 cm in length in
      the proximal ureter of 6 patients who received treatment in the Affiliated Renji
      Hospital of Shanghai Jiaotong University School of Medicine between December 2010
      and February 2017. The length of fibroepithelial polyps ranged from 5.8 to 8.2
      cm. There were 4 males and 2 females with the mean age of 32.6 +/- 9.8 years.
      Unilateral polyps were found in all patients (right: n = 4; left: n = 2).
      Hydronephrosis of different extents was noted in these patients, 4 complained of
      back pain and 2 were diagnosed with hydronephrosis by ultrasonography. 1 patient
      had macroscopic hematuria. All these patients received antegrade plus retrograde
      endoscopic laser polypectomy after admission. Symptoms were significantly
      improved after surgery, and ultrasonography showed hydronephrosis was attenuated
      to different extents 2 weeks later. Three months later, computed tomography
      urography revealed favorable recovery in 5 patients and deterioration of
      hydronephrosis due to ureteropelvic stenosis in 1 patient.

PMID- 30095630
TI  - Does the form of dressings matter?: A comparison of the efficacy in the
      management of postoperative scars between silicone sheets and silicone gel: a
      randomized controlled trial.
AB  - BACKGROUND: Silicone sheet is commonly used for scar management but hard to apply
      to irregular surfaces or mobile areas, and difficult to conceal. On the contrary,
      silicone gel is easy to apply and nearly unnoticeable. Therefore, we conducted
      this study to compare their effectiveness. METHODS: Patients undergoing
      horizontal cesarean section were included. Surgical wounds were divided into 2
      halves. Patients randomly applied silicone sheets and silicone gel on either side
      of their wounds for 3 months. The wounds were assessed at 1, 3, 6, and 12 months
      after surgery. We used the Vancouver Scar Scale (VSS) for an objective evaluation
      and the visual analog scale (VAS) for a subjective evaluation. RESULTS: There was
      no statistical significance between the silicone sheet and silicone gel groups
      with respect to VSS score. The silicone sheet group showed a statistically
      significant higher VAS score for itch at 1 month follow-up (1.18 +/- 2.04 vs 0.35
      +/- 0.85, P = .01). However, the difference was less than 1 on a scale of 10, so
      it might not be clinically meaningful. CONCLUSION: Silicone sheet group showed
      statistically significant worse VAS score in terms of itch. However, the
      difference was too small to be clinically meaningful.

PMID- 30095632
TI  - Prognostic role of tumor-infiltrating lymphocytes in gastric cancer: A systematic
      review and meta-analysis.
AB  - BACKGROUND: The potential prognostic value of tumor-infiltrating lymphocytes
      (TILs) in gastric cancer remains controversial. This meta-analysis examines the
      association between TILs and survival outcomes in gastric cancer. METHODS: Twenty
      two eligible studies were identified using the PubMed and Google Scholar
      databases. The combined sample size of the 22 studies was 2941, and the median
      sample size of the individual studies was 122 patients (52-220). The main
      clinical outcomes examined were overall cancer survival (OCS) and overall cancer
      relapse-free survival (OCRFS). RESULTS: Tumor tissue CD3(+) TILs, indicative of
      pan-T-cell expression, had a positive effect on survival with a hazard ratio (HR)
      of 0.64 (95% confidence interval [CI] 0.52-0.78) for OCS, as did the non-FOXP3(+)
      T-cell subgroup with an HR of 0.66 (95% CI 0.57-0.75), particularly in CD8(+)
      lymphocytes (HR = 0.63, 95% CI 0.48-0.83). On the contrary, high FOXP3(+) T-cell
      expression was correlated with reduced OCS, with an HR of 1.75 (95% CI 1.26
      2.42). Analysis of the seven studies evaluating OCRFS revealed improved OCRFS
      with infiltration of non-FOXP3(+) TILs with an HR of 0.59 (95% CI 0.42-0.81) but
      not FOXP3(+) T lymphocytes with an HR of 1.82 (95% CI 1.30-2.53). CONCLUSION: The
      results from this meta-analysis suggest that high expression of TILs, mainly by
      CD8 lymphocytes, may be a potential prognostic biomarker in patients with gastric
      cancer.

PMID- 30095633
TI  - Diagnostic utility of serological biomarkers in patients with Crohn's disease: A
      case-control study.
AB  - The aim of this study was to examine the expression of serological markers in
      patients with inflammatory bowel disease in China, and determine the diagnostic
      utility of serological markers, individually and in combination, for the
      diagnosis and differential diagnosis of Crohn's disease (CD).Serum samples were
      obtained from 160 participants in Eastern China. Among the participants, 98 were
      diagnosed with CD, 33 had ulcerative colitis (UC), and 29 were healthy controls
      (HC). The serum samples were tested for the presence of antibodies against outer
      membrane porin C (anti-OmpC), Pseudomonas fluorescens bacterial sequence I2 (anti
      I2), anti-laminarin (anti-L), anti-chitin (anti-C), anti-chitobioside
      carbohydrate antibody (ACCA), anti-laminaribioside carbohydrate antibody (ALCA),
      anti-mannobioside carbohydrate antibody (AMCA), and anti-Saccharomyces cerevisiae
      antibody (ASCA) by indirect enzyme-linked immunosorbent assay
      (ELISA).Individually, anti-C, anti-L, ASCA-IgG, and ALCA lacked diagnostic value
      in the differentiation of CD. ASCA-IgA remained the most accurate marker for the
      diagnosis of CD, with an area under the curve (AUC) of 0.77; however, its
      sensitivity and specificity were both lower than 75%. Among the combinations of
      the 5 markers with significant diagnosing ability for CD, combinations with any 2
      of the 3 markers, ASCA IgA, AMCA, and ACCA positive, provided the best accuracy
      in the diagnosis and differential diagnosis of CD (sensitivity and specificity
      both above 75%) and had the highest Youden index.Serological antibodies, when
      considered in combination, have remarkable value in the diagnosis and
      differential diagnosis of CD. Especially, the combination of any 2 of the 3
      markers, ASCA-IgA, AMCA, ACCA positive, appears to be optimal.

PMID- 30095631
TI  - Predictive markers of depression in hypertension.
AB  - Hypertension and depression, as 2 major public health issues, are closely
      related. For patients having hypertension, in particular, depression is a risk
      factor for mortality and jeopardizes their wellbeing. The aim of the study is to
      apply support vector machine (SVM) learning to blood tests and vital signs to
      classify patients having hypertension complicated by depression and patients
      having hypertension alone for the identification of novel markers.Data on
      patients having both hypertension and depression (n = 147) and patients having
      hypertension alone (n = 147) were obtained from electronic medical records of
      admissions containing the records on blood tests and vital signs. Using SVM, we
      distinguished patients having both hypertension and depression from gender- and
      age-matched patients having hypertension alone.SVM-based classification achieved
      73.5% accuracy by 10-fold cross-validation between patients having both
      hypertension and depression and those having hypertension alone. Twelve features
      were selected to compose the optimal feature sets, including body temperature
      (T), glucose (GLU), creatine kinase (CK), albumin (ALB), hydroxybutyrate
      dehydrogenase (HBDH), blood urea nitrogen (BUN), uric Acid (UA), creatinine
      (Crea), cholesterol (TC), total protein (TP), pulse (P), and respiration (R).SVM
      can be used to distinguish patients having both hypertension and depression from
      those having hypertension alone. A significant association was identified between
      depression and blood tests and vital signs. This approach can be helpful for
      clinical diagnosis of depression, but further studies are needed to verify the
      role of these candidate markers for depression diagnosis.

PMID- 30095635
TI  - Anemia is inversely associated with serum C-peptide concentrations in individuals
      with type 2 diabetes.
AB  - The purpose of the study was to test the hypothesis that anemia is related with
      serum C-peptide concentrations in individuals with type 2 diabetes mellitus
      (DM).This cross-sectional study was carried out in 1300 individuals with type 2
      DM. We measured fasting C-peptide, 2-hour postprandial C-peptide, and
      postprandial C-peptide minus fasting C-peptide (DeltaC-peptide) concentrations.
      Anemia was defined as hemoglobin (Hb) concentrations <130 g/L in men and <120 g/L
      in women. Anemia was graded into 2 groups: grade I anemia of Hb concentrations
      >=110 g/L and grade II anemia of Hb concentrations <110 g/L.Fasting C-peptide,
      postprandial C-peptide, and DeltaC-peptide concentrations were lower in
      individuals with anemia. According to the grade of anemia, the average C-peptide
      concentrations differed significantly after adjusting for other covariates. In
      the multivariable model, the statistically significant relation between anemia
      and serum C-peptide concentrations remained after adjusting for confounders,
      including age, gender, family history of diabetes, body mass index, duration of
      diabetes, glycated Hb, free fatty acids, hypertension, and hyperlipidemia
      (fasting C-peptide concentration: beta = -0.057, P = .032; postprandial C-peptide
      concentration: beta = -0.098, P < .001; DeltaC-peptide concentration: beta = 
      0.095, P < .001).Anemia was inversely associated with serum C-peptide
      concentrations in individuals with type 2 DM.

PMID- 30095634
TI  - The function of carbon nanoparticles to improve lymph node dissection and
      identification of parathyroid glands during thyroid reoperation for carcinoma.
AB  - To evaluate the function of carbon nanoparticles during the thyroid reoperation
      for carcinoma, we conducted this study by retrospectively analyzing the data of
      patients who underwent at least completion thyroidectomy with bilateral central
      lymph nodes dissection for thyroid carcinoma from January 2009 to June 2016. The
      clinicopathologic characteristics and surgical details were compared between the
      patient who accepted intraoperative carbon nanoparticles injection and those who
      accepted nothing injection during the surgery. The main monitoring indicators
      were the number of dissected lymph nodes and metastatic lymph nodes in central
      zone, the number of identified parathyroid glands and autoplastic parathyroid
      glands and unintentionally resected parathyroid glands. A total of 69 patients
      were enrolled into the carbon nanoparticles group and 128 patients were enrolled
      into the control group.The average number of lymph nodes harvested in the central
      zone was higher in the carbon nanoparticles group than that in the control group
      (11.2 +/- 5.7 vs 7.7 +/- 4.0, P < .001), so was the average number of metastatic
      lymph nodes (4.5 +/- 4.5 vs 2.7 +/- 2.9, P = .004). The average number of
      identified parathyroid gland was greater in the carbon nanoparticles group than
      that in the control group (2.4 +/- 1.2 vs 1.6 +/- 1.1, P < .001). The average
      number of autoplastic parathyroid gland was comparable between the 2 groups (0.6
      +/- 0.6 vs 0.4 +/- 0.7, P = .052). But the average number of unintentionally
      resected parathyroid gland was less in the carbon nanoparticles group than that
      in the control group (0.1 +/- 0.2 vs 0.2 +/- 0.4, P = .007). Carbon nanoparticles
      can improve lymph nodes dissection and identification of parathyroid gland during
      thyroid reoperation for carcinoma.

PMID- 30095636
TI  - Unusual bleeding from hepaticojejunostomy controlled by side-to-side splenorenal
      shunt: A case report.
AB  - RATIONALE: Ectopic variceal bleeding due to hepaticojejunostomy (HJ) is unusual
      and difficult to manage. Reports on the use of side-to-side splenorenal shunt for
      severe bleeding from varices at HJ anastomosis are lacking. PATIENT CONCERNS: A
      43-year-old man was admitted to our hospital with repeated episodes of
      hematemesis. He has a history of right hemihepatectomy with HJ reconstruction to
      the left hepatic duct for hilar cholangiocarcinoma. Two years after surgery, he
      presented with repeated episodes of hematemesis and underwent blood transfusion.
      DIAGNOSES: Imaging tests and endoscopic investigation failed to identify the
      bleeding source. When conservative management failed to control his bleeding, he
      underwent emergency laparotomy, which revealed hemorrhage from ectopic varices at
      the HJ anastomosis. INTERVENTIONS: To arrest the bleeding, a side-to-side
      venovenal anastomosis was created between the splenic and left renal veins to
      form a shunt for decompression of the varices at the HJ anastomosis. OUTCOMES:
      After the surgery, the patient's symptoms ceased, and a no bleeding in the
      digestive tract was noted at 2-year follow-up. LESSONS: The present patient is
      the first reported case of unusual bleeding from HJ controlled by a side-to-side
      splenorenal shunt. We believe this approach is a useful and effective surgical
      treatment for severe bleeding from varices at the HJ anastomosis.

PMID- 30095638
TI  - General anesthesia versus local anesthesia for endovascular aortic aneurysm
      repair.
AB  - The aim of this study was to compare general and local anesthesia techniques in
      patients treated with elective endovascular aortic aneurysm repair (EVAR) for
      infrarenal aortic aneurysms.In this single-center, observational cohort study, in
      all, 259 consecutive patients who underwent elective EVAR was included; 144
      patients (55.6%, 126 men, mean age 72.8 years) operated on under general
      anesthesia (GA group) and 115 (44.4%, 100 men, mean age 72.3 years) operated on
      under local anesthesia (LA group). A retrospective analysis regarding technical
      feasibility, endoleaks, length of hospital stay, and 30-day clinical outcomes was
      performed.There was no anesthetic conversion (from LA to GA) during EVAR, and no
      significant difference was noted in the incidence of endoleaks and its types in
      relation to anesthetic techniques on final completion angiograms (14.1% vs 18.4%;
      P = .347) and follow-up computed tomography angiogram at 30 days after EVAR
      (23.6% vs 19.1%; P = .384). Significant differences were not observed with regard
      to a prolonged length of hospital stay in relation to anesthetic techniques (8.6
      +/- 16.3 vs 7.2 +/- 3.3; P = .348), and the main outcomes showed no significant
      differences in morbidity (20.1% vs 16.5%; P = .457), mortality (0.0% vs 0.0%),
      and the rates of secondary therapeutic procedures (9.7% vs 4.3%; P = .099)
      between the 2 groups during the 30-day follow-up.We have not shown a definite
      difference in 30-day outcomes between GA and LA for EVAR. The anesthetist and
      surgeon, in consultation with the patient, should decide which anesthetic
      technique to use on an individual basis.

PMID- 30095637
TI  - The effects of respiratory inhaled drugs on the prevention of acute mountain
      sickness.
AB  - BACKGROUND: Acute mountain sickness (AMS) is common in high-altitude travelers,
      and may lead to life-threatening high-altitude cerebral edema (HACE) or high
      altitude pulmonary edema (HAPE). The inhaled drugs have a much lower peak serum
      concentrations and a shorter half-life period than oral drugs, which give them a
      special character, greater local effects in the lung. Meanwhile, short-term
      administration of inhaled drugs results in almost no adverse reactions. METHODS:
      We chose inhaled ipratropium bromide/salbutamol sulfate (combivent, COM),
      budesonide (pulmicortrespules, BUD), and salbutamol sulfate (ventolin, VEN) in
      our study to investigate their prophylactic efficacy against AMS. Since COM is a
      compound drug of ipratropium bromide and salbutamol sulfate, to verify which part
      of COM plays a role in the prevention of AMS, we also tested VEN in our
      experiment. RESULTS: In our study, Lake Louise scores (LLS) in the COM (1.14 +/-
      0.89 vs 1.91 +/- 1.23, P < .05) and BUD (1.35 +/- 0.94 vs 1.91 +/- 1.23, P < .05)
      groups were both significantly lower than the placebo group at 72 hours. There
      were no significant differences in LLS scores among the 4 groups at 120 hours.
      The incidence of AMS in the COM group was significantly reduced at 72 hours
      (16.7% in COM group vs 43.4% in placebo group, P < .05) after exposure to high
      altitude. There were no significant differences in AMS incidences at 120 hours
      among the 4 groups. CONCLUSION: The prophylactic use of COM could prevent AMS in
      young Chinese male at 72 hours after high-altitude exposure. BUD also could
      reduce LLS but not prevent AMS at 72 hours. Ipratropium bromide maybe the
      effective drug in COM work on the prevention of AMS alone.

PMID- 30095639
TI  - HLA-DRB1 polymorphisms and alopecia areata disease risk: A systematic review and
      meta-analysis.
AB  - BACKGROUND: Published studies have reported conflicting and heterogeneous results
      regarding the association between human leukocyte antigen (HLA)-DRB1
      polymorphisms and alopecia areata (AA). This study aimed to review and
      quantitatively analyze the association between HLA-DRB1 polymorphisms and AA.
      METHODS: In this study, all relevant publications were searched through December
      2016. Odds ratios (ORs) and confidence intervals (CIs) for comparisons between
      case and control groups were calculated. Stata 14.0 software was used to perform
      statistical analysis. This research does not require formal ethical approval
      because the data used in this analysis do not involve personal information and
      thus do not affect privacy. RESULTS: Twelve articles were identified. For HLA
      DRB1*04 and HLA-DRB1*16 polymorphisms, the OR (95% CIs) was 1.49 (1.24-1.78) and
      1.61 (1.08-2.41), and P was <.01 and <.01, respectively. For HLA-DRB1*0301, HLA
      DRB1*09, and HLA-DRB1*13 polymorphisms, the OR (95% CIs) was 0.42 (0.28-0.63),
      0.74 (0.55-0.99), and 0.62 (0.40-0.98), and P was <.01, <.01, and <.01,
      respectively. Statistical evidence revealed no publication bias (P > .05).
      CONCLUSION: The present meta-analysis suggested that HLA-DRB1*04 and HLA-DRB1*16
      polymorphisms might be associated with increased AA risk, while HLA-DRB1*0301,
      HLA-DRB1*09, and HLA-DRB1*13 polymorphisms might decrease the AA risk. Studies
      with adequate methodological quality on gene-gene and gene-environment
      interactions are needed to validate the results in the future.

PMID- 30095640
TI  - Current evidence of acupuncture for symptoms related to breast cancer survivors:
      A PRISMA-compliant systematic review of clinical studies in Korea.
AB  - BACKGROUND: Breast cancer survivors experience various symptoms associated with
      their cancer interventions, and the benefits of acupuncture for these symptoms
      have been evaluated in clinical trials worldwide. The purpose of this review was
      to discuss the current status of clinical research regarding the use of
      acupuncture as a part of traditional Korean medicine (KM) for various symptoms
      associated with breast cancer therapies. METHODS: We conducted a systematic
      review of the literature regarding the use of acupuncture as a part of
      traditional KM to treat symptoms associated with breast cancer therapies. The
      following databases were searched for content up to February 2017: MEDLINE,
      EMBASE, the Cochrane library, 4 Korean databases, and conference proceedings from
      major Korean medical societies. RESULTS: Among the 1228 identified articles, 8
      observational studies (3 case series and 5 case reports), and 1 randomized
      controlled trial (RCT) were included in this review. Among these studies, 3
      investigated lymphedema, 2 investigated chemotherapy-induced peripheral
      neuropathy, 1 investigated hot flushes, 1 investigated constipation, and 2
      investigated miscellaneous symptoms in breast cancer survivors; all studies
      concluded that acupuncture can alleviate the symptom in question. However, we
      identified only 1 relevant RCT, and the included studies had limitations in terms
      of reporting quality. CONCLUSION: There is a lack of conclusive evidence
      regarding the benefits of acupuncture for the treatment of breast cancer
      survivors in Korea. More rigorous RCTs are necessary in the future to establish
      stronger clinical evidence regarding the use of acupuncture to better reflect the
      clinical context of Korea.

PMID- 30095642
TI  - The birth weight in pregnant women with Asherman syndrome compared to normal
      intrauterine cavity: A case-control study.
AB  - Women with Asherman syndrome (AS) have damaged endometrium and reduced blood flow
      to the uterus and placenta which may lead to low birth weight and several
      obstetric complications.The objective is to determine the association between low
      birth weight and obstetrical complications in women with AS compared to women
      with normal intrauterine cavity.A retrospective case-control study was conducted
      in Women's Specialized Hospital, King Fahad Medical City, from December 2008 to
      December 2015. Pregnant women with AS undergoing hysteroscopic adhesiolysis who
      presented to our clinic were matched for age, parity, body mass index, methods of
      conception, and gestational age to pregnant women without AS based on a 1:3
      ratio. The main outcome measure included birth weight and obstetrical
      complications.The study included 56 women with 14 cases and 42 controls. Pregnant
      women with AS had significantly lower birth weight (2.23 +/- 0.28 kg) compared
      with pregnant women without AS (3.13 +/- 0.383 kg) (P < .001 odds ratio [OR]
      0.029, 95% confidence interval [CI] 0.006-0.148, P = .001). Complications of
      delivery including retained placenta, placenta previa, and fetal death were
      significantly higher in patients with AS compared with controls 28.6% 7.1%, and
      7.1% compared to 4.8%, 0%, and 0%, respectively. This was statistically
      significant (P < .001).Pregnant women with AS delivered low birth weight newborns
      and had more obstetrical complications as compared with pregnant women with
      normal cavity.

PMID- 30095643
TI  - Suprapatellar versus infrapatellar intramedullary nailing for treatment of tibial
      shaft fractures in adults.
AB  - BACKGROUND: Numerous studies have compared suprapatellar (SP) nailing to
      infrapatellar (IP) nailing for treatment of tibial shaft fractures; however, the
      best strategy remains controversial. The aim of this meta-analysis is to assess
      whether SP or IP nailing is more effective for tibial shaft fractures in adults.
      METHODS: Literature searches of PubMed, Embase, OVID, Cochrane Library, Web of
      Science, Chinese Biomedical Literature, Wanfang, Weipu Journal, and CNKI
      databases were performed up to July 2017. Only randomized controlled trials
      (RCTs) comparing SP versus IP intramedullary nailing for tibial shaft fractures
      were included. Data collection and extraction, quality assessment, and data
      analyses were performed according to the Cochrane standards. RESULTS: Twelve RCTs
      were selected for analysis. SP intramedullary nailing reduced knee joint pain,
      visual analog score, fluoroscopy time, and sagittal angle, resulting in better
      Harris hip score, Lysholm knee score, short-form 36 questionnaire, range of
      motion, and rates of "excellent" and "good" outcome. There were no significant
      differences in operative time, blood loss, length of hospital stay, union time,
      and coronal angle between groups. CONCLUSION: The present meta-analysis indicates
      that SP intramedullary nailing has obvious advantages over IP intramedullary
      nailing for treatment of tibial shaft fractures in adults. However, owing to the
      low-quality evidence currently available, additional high-quality RCTs are needed
      to confirm these findings.

PMID- 30095641
TI  - Serum procalcitonin levels can be used to differentiate between inflammatory and
      non-inflammatory diarrhea in acute infectious diarrhea.
AB  - In this study, we assess the possibility of using procalcitonin levels to
      differentiate between inflammatory diarrhea and non-inflammatory diarrhea in
      acute infectious diarrhea.We reviewed the records of 1176 patients who had
      symptoms of diarrhea, fever (>=37.8  degrees C), and abdominal pain between March
      2011 and May 2015. After applying exclusion criteria, a sample of 514 patients
      was considered for study. The patient sample was divided into Group A and Group B
      for inflammatory diarrhea and non-inflammatory diarrhea, respectively. The
      assessment involved comparing the laboratory characteristics with the clinical
      characteristics of the groups.The characteristics of Group A, such as white blood
      cell (WBC), C-reactive protein (CRP), absolute neutrophil count (ANC), and
      procalcitonin levels, were relatively higher than those of Group B (P < .001 for
      Group A). A receiver operator characteristic (ROC) analysis revealed that the
      highest area-under-the-curve (AUC) value of procalcitonin (0.797; 95% confidence
      interval [CI] [0.760, 0.831]; P < .001), could be used to differentiate between
      the 2 groups. Procalcitonin exhibited a sensitivity and a specificity of 87.03%
      and 68.75%, respectively, at a 0.08 ng/mL cut-off level.Procalcitonin was a good
      candidate biomarker of inflammatory diarrhea than other inflammatory markers.

PMID- 30095644
TI  - Proposal for subclassification to select patients for hepatectomy with
      intermediate hepatocellular carcinoma and Child-Pugh A liver function: A double
      center study from China.
AB  - Increasing evidence has shown that hepatectomy provides a longer overall survival
      (OS) for patients with hepatocellular carcinoma (HCC) in the intermediate stage.
      Unfortunately, not all patients benefit from liver resection, even if hepatectomy
      is feasible. This study aimed to propose a subclassification to select patients
      for surgical resection.OS of patients with intermediate-stage HCC who underwent
      hepatectomy at Beijing Friendship Hospital or Peking Union Medical College
      Hospital were reviewed. Patients were divided into 2 groups based on the results
      of survival analysis. The prognosis of these patients was compared with that in
      those who were treated by trans-arterial chemoembolization (TACE) in each
      subgroup.A total of 259 patients with intermediate-stage HCC who were initially
      treated by hepatectomy were included. Multivariate analysis showed that
      cumulative tumor size and tumor number independently affected tumor recurrence
      and survival time of these patients. Patients were then divided into group A
      (tumor size <11 cm and tumor number < 4; n = 205) and group B (tumor size >=11 cm
      and tumor number >= 4; n = 54). Multivariate analysis showed that hepatectomy was
      independently associated with longer OS compared with TACE in patients in group A
      (hazard ratio = 0.67, 95% confidence interval = 0.49-0.90), but not in group
      B.Surgical management of intermediate-stage HCC should be performed with more
      complexity than current practice. Hepatic resection could be considered as the
      first-line treatment only for patients with HCC who have a cumulative tumor size
      of less than 11 cm and <4 tumors.

PMID- 30095645
TI  - Imaging findings of inflammatory myofibroblastic tumor in breast: A case report.
AB  - RATIONALE: Inflammatory myofibroblastic tumors (IMTs), particularly breast IMTs,
      are rare neoplastic lesions typically associated with a favorable prognosis.
      Breast IMTs are easily misdiagnosed as other types of malignant lesions, and
      therefore there is a significant unmet need for a better preoperational
      differential diagnosis based on imaging manifestations. Here, we report the
      imaging findings of a breast IMT and compare our findings with previously
      published features of breast IMTs. PATIENT CONCERNS: The patient, a 43-year-old
      female, reported the presence of a palpable lump within her left breast. An
      ultrasound examination revealed an irregular hypoechoic mass with unclear
      boundaries. Mammography demonstrated a mass of heterogeneous and striped density
      with granular calcification. Magnetic resonance image (MRI) inspection displayed
      an irregular tissue lump with an undistinguishable boundary and a further dynamic
      contrast-enhanced MRI disclosed an associated efflux change. DIAGNOSES: Breast
      inflammatory myofibroblastic tumors. INTERVENTIONS: Breast needle biopsy and
      mammary resection were performed. Pathological staining of the bulk resected
      tumor after preoperative preparation revealed that the tumor-like tissue was
      enriched for spindle cells arranged in fascicular clusters. Histopathological
      diagnosis and immunohistochemistry confirmed the mass as being a breast IMT.
      OUTCOMES: No metastatic recurrence was found during 6-month or 1-year follow-ups.
      LESSONS: Breast IMTs commonly develop in elderly women with atypical imaging
      features. They are primarily composed of lobular soft tissues infiltrated with an
      abundant focal blood supply and granular calcification. Development of breast
      IMTs is closely related to trauma. A preliminary diagnosis of such masses can be
      made based on combined manifestations of both clinical and imaging features,
      while a final confirmation still requires pathological staining. Imaging
      examinations are of value for such tumors to define the lesion edges and their
      associations with adjacent tissues.

PMID- 30095646
TI  - Primary kidney malignant epithelioid angiomyolipoma: Two cases report and review
      of literature.
AB  - RATIONALE: Epithelioid angiomyolipoma (EAML) is a subtype of angiomyolipoma with
      malignant potential. A diagnosis of malignant EAML of the kidney is based on
      extrarenal metastasis, and predicting early transformation is difficult. To
      propose criteria for indicators of malignant transformation, herein we report 2
      cases and review 17 cases reported in the literature (2000-2017). PATIENT
      CONCERNS: Tumor of the kidney was determined in 2 patients, and tissues after
      nephrectomy were pathologically, histologically, and immunochemically examined.
      DIAGNOSIS: Malignant EAML. INTERVENTION: The 2 present patients were treated with
      nephrectomy only. OUTCOMES: Case 1 involved a 48-year-old woman with a 7.5-cm
      solid mass in the right kidney who underwent nephrectomy. CT detected a mass in
      the liver after 13 months, which was speculated to be metastasis from the kidney
      lesion. Case 2 involved a 62-year-old man with a 7-cm cystic solid mass in the
      left kidney who accepted nephrectomy and at 10 months post-surgery lived with no
      disease. Both cases presented a large tumor, atypical epithelioid cells, mitotic
      figures, and necrosis; tested positive for melanocytic markers (HMB45, MelanA).
      LESSONS: The literature review of malignant EAML led to the identification of 8
      malignant features: size >=5 cm; metastasis; infiltration; necrosis; >=50%
      atypical epithelioid cells; cytologic atypia; atypical mitosis; and vessel
      invasion. The co-existence of at least 5 of these is proposed to indicate
      malignant EAML. Features of our 2 new cases of primary malignant EAML of the
      kidney matched these criteria. Our proposal of criteria for predicting malignant
      feature, based on 2 new cases and 17 cases in the literature, should aid
      understanding and avoid misdiagnosis. Nephrectomy is currently the common
      treatment strategy for malignant EAML, but more effective treatment strategies
      are needed to provide a better prognosis for patients.

PMID- 30095647
TI  - Successful removal of giant mediastinal lipoma and liposarcoma involving both
      chest cavities: Two case reports.
AB  - RATIONALE: Surgical removal of a giant mediastinal lipoma or liposarcoma
      involving both chest cavities is always challenging. PATIENT CONCERNS: We present
      2 cases of giant mediastinal tumor, one of which was a 22-year-old female who was
      admitted to our hospital due to a mild dyspnea after running. Computed tomography
      (CT) scan revealed a large mass with low density occupying the entire right
      hemithorax and extending anteriorly into the left. The other patient was a 43
      year-old male, who was presented to the hospital with complaints of gradually
      progressive dyspnea. CT scan revealed a mass comprised of fat density with areas
      of soft-tissue density in-between, involving in both chest cavities, draping
      around the heart and great vessels. INTERVENTIONS: Both of the patients receive
      complete resection through a standard median sternotomy. DIAGNOSES: Histologic
      examination revealed lipoma for the first patient, and well differentiated
      liposarcoma for the second. OUTCOMES: Both of their symptoms were improved after
      surgery and the postoperative courses were good. LESSONS: Our experience
      indicated that complete surgical removal through a standard median sternotomy is
      a safe and efficient approach for the treatment of giant mediastinal lipoma and
      liposarcoma.

PMID- 30095648
TI  - Association of obesity and risk of diabetic retinopathy in diabetes patients: A
      meta-analysis of prospective cohort studies.
AB  - BACKGROUND: Diabetic retinopathy (DR) was considered to be a common complication
      of diabetes. The purpose of the current study was to investigate the potential
      association between obesity and DR risk by conducting a meta-analysis of
      prospective studies. METHODS: A consummate literature search of PubMed, EMBASE,
      and web of science was conducted until July 2016. A total of 13 prospective
      cohort studies were included in this meta-analysis. RESULTS: On meta-analysis of
      all the studies assessing DR risk, obesity was associated with a significant
      increase in DR incidence (relative risk [RR], 1.20; 95% confidence interval [CI],
      1.01-1.43; I = 59.6%). When only proliferative DR (PDR) was considered, no
      significant association between obesity and risk of PDR was detected. Significant
      harmful effect was detected in type 2 diabetes mellitus (T2DM) group (RR, 1.40;
      95% CI, 1.05-1.87; I = 67.6%) but not mixed group (RR, 1.04; 95% CI, 0.97-1.18; I
      = 0.00%). No significant publication bias was detected in the selected 13
      studies. CONCLUSION: Obesity was a risk factor for non-proliferative DR. However
      additional well-designed and well-conducted epidemiologic studies were required
      to deepen our understanding of the relation between obesity and DR.

PMID- 30095649
TI  - Survey of family satisfaction with intensive care units: A prospective
      multicenter study.
AB  - Although family satisfaction is an important indicator for quality improvement of
      intensive care units (ICUs), few studies have translated family satisfaction data
      into quality improvement in Asia. A prospective multicenter study was conducted
      to evaluate family satisfaction regarding the care of patients and their
      family.The family satisfaction in the ICU (FS-ICU) questionnaire was administered
      from January 2015 to February 2016 at ICUs of 3 tertiary teaching hospitals in
      South Korea. Family members of adult patients, staying at an ICU for >=48 hours,
      were included. Key factors affecting satisfaction were identified using
      quantitative and qualitative analyses.In total, 200 family members participated
      in this survey. The mean score for overall family satisfaction (FS-ICU/total) was
      75.4 +/- 17.7. The mean score for satisfaction with information/decision-making
      was greater than that for satisfaction with care (78.2 +/- 18.2 vs 73.5 +/- 19.4;
      P <= .001). Family members who agreed to not resuscitate and whose patient died
      at the ICU had lower FS-ICU/total scores. When compared with hospital A, hospital
      C was an independent predictor with an FS-ICU/total score of <75. Families
      reported the least satisfaction for the atmosphere of the ICU, including the
      waiting room atmosphere and management of agitation.We evaluated family
      satisfaction regarding ICUs for the first time in Asia using a validated tool.
      The decision to not resuscitate, ICU mortality, and ICU culture were associated
      with family satisfaction with critical care. Efforts should be targeted for
      improving factors that cause low family satisfaction when planning quality
      improvement interventions for ICUs in Asia.

PMID- 30095650
TI  - A case report of pulmonary arterial hypertension in pregnancy and complications
      of anticoagulation therapy.
AB  - RATIONALE: Treprostinil, a potent vasodilator, is the treatment of choice for
      severe pulmonary arterial hypertension (PAH) during pregnancy. Its inhibition of
      platelet aggregation increases the risk of hemorrhage. In addition,
      anticoagulation therapy is widely used in pregnancy with PAH due to the
      hypercoagulable state. However, very little is known about the complications of
      anticoagulants' use in pregnancy with PAH. PATIENT CONCERNS: A 27-year-old
      pregnant woman was admitted to the hospital at 32weeks with progressive dyspnea.
      DIAGNOSES: The pregnant was diagnosed with ventricular septal defect 12 years
      prior to presentation. Combining clinical manifestation with results of right
      heart catheterization (RHC) and echocardiography, it was consistent with severe
      World Health Organization (WHO) group I PAH. INTERVENTIONS: Supportive treatment
      included supplemental oxygen, intravenous treprostinil, sildenafil and
      prophylactic anticoagulation. OUTCOMES: Gastrointestinal bleeding is occurred in
      our patient when dalteparin were used in conjunction with treprostinil. Her care
      was further complicated refractory to usual conservative measures before
      delivery. LESSONS: This case report illustrates the complexities that arise when
      prostacyclin therapies are combined with necessary anticoagulation in patients
      with PAH during pregnancy. More intention should play to the complications of
      anticoagulant in pregnancy with PAH during treprostinil therapy.

PMID- 30095651
TI  - Combined laparoscopic and hysteroscopic management of cesarean scar pregnancy
      with temporary occlusion of bilateral internal iliac arteries: A case report and
      literature review.
AB  - RATIONALE: Cesarean scar pregnancy is a rare event that carries a risk of heavy
      hemorrhage and emergency hysterectomy. Many treatment modalities have been
      reported, but with no consensus. Here we report a case of combined laparoscopic
      and hysteroscopic treatment with temporary occlusion of the bilateral internal
      iliac arteries. PATIENT CONCERNS: A 28-year-old woman presented with amenorrhea
      diagnosed as an 11-week cesarean scar pregnancy after an unsuccessful abortion.
      The patient's serum human chorionic gonadotropin level was 40,542 mIU/mL.
      Magnetic resonance imaging revealed a mass measuring 5 * 4.5 cm over the anterior
      uterine isthmus. DIAGNOSE: Type III cesarean pregnancy. INTERVENTIONS: Diagnostic
      and operative laparoscopy were performed to remove the pregnancy tissue and
      repair the scar dehiscence after temporary occlusion of the bilateral internal
      iliac arteries, followed by hysteroscopy to confirm no pregnancy remnants and to
      free intrauterine adhesions. OUTCOMES: Intraoperative and postoperative bleeding
      were minimal. The postoperative recovery was uneventful. Human chorionic
      gonadotropin normalized after 3 weeks. LESSONS: Temporary occlusion of the
      bilateral internal iliac arteries seems to be a good strategy to reduce
      hemorrhage in cesarean scar pregnancy. Hysteroscopy is necessary to deal with
      intrauterine lesions.

PMID- 30095652
TI  - Risk factors for increased postoperative drainage of calcaneal fractures after
      open reduction and internal fixation: An observational study.
AB  - Sufficient drainage is very important for preventing wound complications after
      open reduction and internal fixation (ORIF) of calcaneal fractures. However, the
      drainage amount varies among patients. The objective of this study was to
      identify factors associated with increased postoperative drainage after ORIF of
      calcaneal fractures.A retrospective study including 87 patients with 92 calcaneal
      fractures in our hospital was performed. Patients were divided into 2 groups
      based on whether they had increased drainage, which was defined as a total
      drainage of >=340 mL (50th percentile). We gathered the following data on each
      patient: age; sex; smoking history; body mass index (BMI); American Society of
      Anesthesiologists (ASA) classification; fracture type; the time from injury to
      surgery; operative time; bone grafting; preoperative labs including prothrombin
      time (PT), activated partial thromboplastin time (APTT), hematocrit, and D-dimer
      level; and histories for hypertension, diabetes, and heart disease. Univariate
      analysis and multivariate logistic regression analysis were used to analyze the
      risk factors associated with increased drainage.Total drainage ranged from 105 to
      1185 mL, and the average drainage for this cohort was 393.6 +/- 232.4 mL (mean +/
      standard deviation). 57.6% (n = 53) of patients had increased drainage. Smoking
      history, Sanders type, operative time, and bone grafting were significantly
      associated with increased drainage on univariate analysis. Multivariate logistic
      regression analysis then demonstrated that active smoking and higher Sanders type
      were independent risk factors for increased drainage.Patients with calcaneal
      fractures who smoked or had a higher level of Sanders type had a higher risk of
      increased postoperative drainage. Therefore, we suggest that active precautions
      be taken for these patients to reduce the rate of postoperative wound
      complications.

PMID- 30095653
TI  - Retrospective study to identify risk factors for chronic kidney disease in
      children with congenital solitary functioning kidney detected by neonatal renal
      ultrasound screening.
AB  - To evaluate the prognostic significance of factors frequently associated with a
      reduction in renal mass, such as prematurity, low birth weight, and congenital
      anomalies of kidney and urinary tract (CAKUT), in patients with solitary
      functioning kidney (SFK) and investigate signs of early renal injury due to
      glomerular hyperfiltration damage or dysplasia in the remaining
      kidney.Retrospective observational study of congenital SFK diagnosed and followed
      at a tertiary care hospital over a period of 10 years in which 32,900 newborns
      underwent routine neonatal abdominal ultrasound screening. We analyzed age at
      diagnosis, sex, gestational age, anthropometric measurements at birth and
      prenatal and neonatal ultrasound findings, in addition to follow-up data
      corresponding to imaging findings (ultrasound, micturating cystourethrography,
      dimercaptosuccinic acid renal, and scintigraphy), ipsilateral CAKUT, compensatory
      hypertrophy, and renal injury in the form of albuminuria, blood pressure, and
      estimated glomerular filtration rate (eGFR).In total, 128 congenital SFK cases
      were detected (1 per 257 live births). Of these, 117 (91.4%) were diagnosed by
      neonatal ultrasound screening and 44.5% of these had been previously identified
      by prenatal ultrasound. Neonatal ultrasound had a specificity of 100% and a
      sensitivity of 92.1%. Forty-five patients (35.2%) had ipsilateral CAKUT and the
      most common type was urinary collecting system anomalies (75.5%). Over a median
      follow-up of 6.3 years (1-10 years), compensatory renal hypertrophy was observed
      in 81 patients (63.7%), most of whom had ipsilateral CAKUT (76.1% vs 56.6% of
      patients without ipsilateral CAKUT). Albuminuria and hypertension were observed
      in 3.12% and 5% of patients, respectively, and both were associated with
      ipsilateral CAKUT (P < .05). In addition, 75% of albuminuria cases (P = .031),
      83.3% of hypertension cases (P = .004), and 100% of decreased eGFRcases (P =
      .031) were significantly associated with CAKUT (renal parenchymal anomaly
      category), being the strongest predictor of GFR the presence or absence of
      CAKUT.Neonatal ultrasound screening is useful for the early diagnosis of SFK. The
      presence of ipsilateral CAKUT should be evaluated in all patients with SFK as
      congenital anomalies of the renal parenchyma are associated with a poorer
      prognosis. Because morbidity from CAKUTs may not develop until adulthood,
      patients should be closely followed throughout life.

PMID- 30095654
TI  - Effect of lateral internal sphincterotomy in patients undergoing excisional
      hemorrhoidectomy.
AB  - BACKGROUND: Excisional hemorrhoidectomy (EH) is the major surgical option for
      high-grade symptomatic hemorrhoids, but it has some shortcomings, especially
      postoperative pain. This study was performed to assess the effect of lateral
      internal sphincterotomy (LIS) in patients undergoing excisional hemorrhoidectomy.
      METHODS: A systematic literature search (Medline, Embase, Cochrane Library,
      Science Citation Index, Science Direct, Springer Link, Ovid Journals, and EBSCO)
      was performed to identify all eligible articles. Randomized controlled trials
      (RCTs) published until July 7, 2017 comparing EH combined with LIS (experimental
      group) with EH only (control group) were eligible for inclusion. The primary
      outcome of interest was postoperative pain. RESULTS: Ten RCTs involving 1560
      patients were identified for inclusion. The pooled analysis revealed that
      patients undergoing EH and LIS were associated with lower pain score
      [standardized mean difference (SMD), -0.75; 95% confidence interval (CI), -1.14
      to -0.36; z = 3.76; P = .0002] and resting anal pressure [odds ratio (OR), 
      17.19; 95% CI, -25.66 to -8.72; z = 3.98; P < .0001], and lower incidence of anal
      stricture (OR, 0.12; 95% CI, 0.03-0.53; z = 2.85; P = .004). However, the
      differences of urinary retention, bleeding and length of hospital stay were
      similar between the 2 methods. CONCLUSION: Our meta-analysis suggests that LIS
      effectively relieves postoperative pain and reduces patient's postoperative
      analgesic requirements. LIS also reduces the incidence of anal stenosis but
      increases the incidence of fecal incontinence.

PMID- 30095655
TI  - Does B7-H4 expression correlate with clinicopathologic characteristics and
      survival in ovarian cancer?: A systematic review and PRISMA-compliant meta
      analysis.
AB  - BACKGROUND: Several studies have shown that B7-H4 expression is significantly
      increased in ovarian cancer. However, the role of B7-H4 expression in ovarian
      cancer remains unclear, and some studies reporting conflicting results. A
      systematic review of the literature and meta-analysis were conducted to assess
      the clinicopathologic characteristics and prognostic significance of B7-H4 in
      ovarian cancer. METHODS: Eligible studies were searched in the PubMed, MEDLINE,
      Cochrane Library, and the China National Knowledge Infrastructure databases. The
      included studies assessed the relationship between B7-H4 expression and
      clinicopathologic features or prognosis in patients with ovarian cancer through
      September 2017. A total of 1045 patients in 10 studies were included in the meta
      analysis. Stata software version 12.0 was used to analyze the data. We used an
      odds ratio (OR) or hazard ratio (HR) with a 95% confidence interval (CI) to
      assess the risk or hazard association. RESULTS: B7-H4 expression in ovarian
      cancer patients was significantly increased (OR: 4.20, 95% CI: 2.85-6.18, Z =
      6.91, P < .05), and heterogeneity was low between studies (I = 8.2%, P = .366).
      With respect to the clinicopathologic features, no relation was detected between
      B7-H4 expression and International Federation of Gynaecology and Obstetricsstages
      stages (OR: 0.81, 95% CI: 0.64-1.03, Z = 1.70, P = .09), pathologic grade (OR:
      0.91, 95% CI: 0.72-1.16, Z = 0.76, P = .45), tumor metastasis (OR: 1.25, 95% CI:
      0.90-1.74, Z = 1.34, P = .18), or histologic type (OR: 1.17, 95% CI: 0.85-1.60, Z
      = 0.96, P = .34) in ovarian cancer. Furthermore, B7-H4 expression was
      significantly associated with a worse progression-free survival (PFS) (HR: 1.30,
      95% CI: 1.17-1.45, Z = 4.79, P < .05). CONCLUSION: B7-H4 expression was related
      to ovarian cancer, but not to patients' clinicopathologic characteristics. High
      B7-H4 expression was negatively correlated with survival outcome, suggesting that
      B7-H4 plays an essential role in poor prognosis in ovarian cancer patients.

PMID- 30095656
TI  - Influence of different drug delivery methods for Endostar combined with a
      gemcitabine/cisplatin regimen in locally advanced or metastatic lung squamous
      cell carcinoma: A retrospective observational study.
AB  - Continuous endovenous administration of Endostar (CE) gradually replaced drip
      intravenous administration of Endostar (DE) in lung squamous cell carcinoma (SCC)
      treatment presently, but the efficacy and safety of CE and DE which is better in
      advanced lung SCC are yet unclear. To evaluate the feasibility of CE as an
      alternative to DE with gemcitabine/cisplatin (GP) chemotherapy. Data were
      collected from patients admitted with locally advanced or metastatic lung SCC
      from January 2011 to April 2015, including the patients' characteristics, the
      therapeutic regimen, the treatment effectiveness, and toxicity. There are 71
      patients with pathologically confirmed lung SCC retrospectively assigned to a
      treatment (CE) group of 48 patients and a control (DE) group of 23 patients. The
      response of each tumor to the therapy was assessed every 2 cycles by a chest and
      upper abdomen computed tomography for the comparison of curative effects and
      adverse reactions. Compared with the DE group, the response rate and disease
      control rate were noninferior in the CE group. The median progression-free
      survival and overall survival in the CE and DE groups were no significantly
      difference (5.5 vs 5.5 months, P = .141; 22.9 vs 14.3 months, P = .053).
      Increased progression-free survival (PFS) for patients in CE group was observed
      across 3 subgroups analyzed. There was a 35.7% reduction in the total dose of
      Endostar per cycle in the CE group compared with that in the DE group. Thus, in
      combination with GP chemotherapy, CE could be a suitable alternative to DE in
      locally advanced or metastatic SCC patients, resulting in less hemoptysis, less
      treatment time, and lower costs.

PMID- 30095657
TI  - Impact of different laminae open angles on axial symptoms after expansive open
      door laminoplasty.
AB  - The present study is a retrospective study.Axial symptoms are frequently
      encountered complication after laminoplasty. Some studies have reported the
      influencing factors and preventive measures of axial symptoms after laminoplasty.
      However, impact of different laminae open angles on the postoperative axial
      symptoms remains unclear.The objective of the present study was to explore the
      effect of different laminae open angles on postoperative axial symptoms and to
      discuss the possible mechanisms of the impact of different open angles on axial
      symptoms.We retrospectively analyzed 124 patients with multilevel cervical
      compression myelopathy who were treated with expansive open-door laminoplasty
      from February 2012 to January 2015. The operational level ranged from C3-C7 in
      all patients. The laminae open angles at the C4, C5, and C6 levels were measured
      1 week postoperative. The mean value was taken for statistical analysis. The
      patients were divided into 2 groups, group A (open angles < 40 degrees , 71
      patients including 44 males and 27 females) and group B (open angles >= 40
      degrees , 53 patients including 32 males and 21 females). C2-C7 Cobb angle, range
      of cervical motion (ROM), Japanese Orthopedic Association (JOA) score, and visual
      analog scale (VAS) score for axial pain were compared between the 2 groups.All
      patients completed at least 2-year follow-up. Both groups gained significant JOA
      improvement postoperatively (P < .05). Preoperative and postoperative C2-C7 Cobb
      angle and ROM comparisons were significantly different (P < .05) in both groups.
      There were no significant difference for other clinical and radiography
      parameters between the groups (P > .05). At 2 weeks and 6 months after surgery,
      there was significant difference in axial symptoms between the 2 groups (P <
      .05). At final follow-up, the difference between the 2 groups was not
      statistically significant (P > .05).In different angles of the lamina open-door,
      incidence of axial symptoms has statistically difference between the 2 groups.
      When the lamina open-door angles are <40 degrees , there are not only ensure
      adequate spinal cord decompression but reduces the incidence of early and midterm
      postoperative axial pain.

PMID- 30095659
TI  - Prophylactic infusion of phenylephrine increases the median effective dose of
      intrathecal hyperbaric bupivacaine in cesarean section: A prospective randomized
      study.
AB  - BACKGROUND: Phenylephrine infusion to prevent spinal-induced hypotension can
      attenuate cephalic spread of intrathecal bupivacaine. Therefore, we suspected the
      intrathecal dose requirement for bupivacaine may differ when using phenylephrine
      infusion to prevent spinal-induced hypotension in cesarean section. We designed a
      prospective, randomized study to determine the ED50 of hyperbaric bupivacaine for
      cesarean section under combined spinal-epidural anesthesia in healthy parturients
      with and without prophylactic phenylephrine infusion to prevent spinal-induced
      hypotension. METHODS: Sixty healthy parturients rated American Society for
      Anesthesiology status I/II undergoing elective cesarean section were enrolled in
      this study, which was conducted July 2016 to February 2017 in the labor and
      delivery department of Jiaxing University Affiliated Women and Children Hospital.
      After enrollment, patients were randomized into 2 groups of 30 by blinded opaque
      envelopes sorted by computer-generated random allocation. Solutions were prepared
      by an anesthesiologist not involved in outcome measurement. Patients and
      anesthesiologists collecting data were blinded to group allocation. Group P
      (phenylephrine group) parturients received prophylactic infusion of phenylephrine
      at the time of intrathecal injection. Group S (saline group) parturients receive
      the same volume of saline. Doses of intrathecal bupivacaine for each patient were
      determined using an up-down allocation method; initial dose was 7 mg. Effective
      dose was defined as bilateral T6 or above sensory block level achieved within 10
      minutes of intrathecal drug administration and no additional epidural lidocaine
      required for intraoperative pain. The Dixon and Massey formula was used to
      calculate ED50 values. RESULTS: The ED50 values for hyperbaric bupivacaine were
      7.0 mg (95% confidence interval [CI]: 6.6-7.4 mg) and 4.9 mg (95% CI: 4.4-5.4 mg)
      for groups P and S, respectively (P < .001). There were significant differences
      in incidence of hypotension and pH of umbilical arterial blood between groups S
      and P (60% vs 10%, P = .04 and 7.31 +/- 0.04 vs 7.28 +/- 0.06, P = .003,
      respectively). CONCLUSION: The ED50 of intrathecal hyperbaric bupivacaine is
      higher when phenylephrine infusion is used to prevent spinal-induced hypotension
      than when it is not used.

PMID- 30095658
TI  - Improving nontechnical skills of an interprofessional emergency medical team
      through a one day crisis resource management training.
AB  - Errors are frequent in healthcare, but Emergency Departments are among the
      highest risk areas due to frequent changes in team composition, complexity and
      variety of cases, and difficulties encountered in managing multiple patients
      simultaneously.Crisis resource management (CRM) training has been associated with
      decreased error rates in the aviation industry as well as in certain areas of
      acute medical care, such as anesthesia and emergency medicine. In this study, we
      assessed whether a single day CRM training, combining didactic and simulation
      sessions, improves nontechnical skills (NTS) of interprofessional emergency
      medical teams.Seventy health professionals with different qualifications, working
      in an emergency department, were enrolled in the study. Twenty individual
      interprofessional teams were created. Each team was assessed before and after the
      training, through 2 in situ simulated exercises. The exercises were videotaped
      and were evaluated by 2 assessors who were blinded as to whether it was the
      initial or the final exercise. They used a new tool designed specifically for the
      assessment of emergency physicians' NTS. The intervention consisted of one-day
      training, combining didactic and simulation sessions, followed by an instructor
      facilitated debriefing. All participants went through this training after the
      initial assessment exercises.A significant improvement (P < 0.05) was shown for
      all the NTS assessed, in all professional categories involved, regardless of the
      duration of prior work experience in the Emergency Department.This study shows
      that even a short intervention, such as a single day CRM training, can have a
      significant impact in improving NTS, and can potentially improve patient safety.

PMID- 30095660
TI  - Does glycopyrrolate premedication facilitate tracheal intubation with a rigid
      video-stylet?: A randomized controlled trial.
AB  - BACKGROUND: A rigid video-stylet intubation device provides safe and accurate
      access to the trachea by enabling visualization of the airway structures during
      tracheal intubation. The primary purpose of this study was to examine the effects
      of glycopyrrolate premedication on tracheal intubation with a rigid video-stylet.
      METHODS: In this prospective, randomized, double-blinded study, 78 patients were
      randomly assigned to the control group (n = 39; no glycopyrrolate administration)
      or the glycopyrrolate group (n = 39; 0.005 mg/kg glycopyrrolate, intramuscular
      injection). A rigid video-stylet was used for tracheal intubation. The degree of
      oral secretion observed through the video-stylet monitor was assessed using the
      OptiScope laryngeal view and graded on a 4-point scale (1, excellent; 2, good; 3,
      poor; and 4, unacceptable). The time to intubation and hemodynamic variables at
      baseline and 1, 3, and 5 minutes after intubation were recorded. RESULTS: The
      OptiScope laryngeal view grades of the glycopyrrolate group (grade 1 = 16
      [41.0%], 2 = 17 [43.6%], 3 = 6 [15.4%], and 4 = 0 [0%]) were significantly higher
      than those of the control group (grade 1 = 9 [23.1%], 2 = 11 [28.2%], 3 = 18
      [46.2%], and 4 = 1 [2.6%]; P = .02). The intubation time was shorter in the
      glycopyrrolate group (18.5 seconds [15.0-22.0]) than the control group (22.0
      seconds [17.9-26.4], P = .02). There was no significant difference in the
      hemodynamic variables between groups. CONCLUSION: Glycopyrrolate facilitated
      tracheal intubation with a rigid video-stylet by decreasing oral secretions and
      providing better visualization and faster intubation with hemodynamic stability.
      TRIAL REGISTRY: www.clinicaltrials.gov; Identifier: NCT03050242.

PMID- 30095661
TI  - Mediastinal and retroperitoneal fibrosis as a manifestation of breast cancer
      metastasis: A case report and literature review.
AB  - RATIONALE: Mediastinal and retroperitoneal fibrosis as a manifestation of
      metastasis from malignancies is rare disease and particularly, cases of
      mediastinal fibrosis have been rarely reported. PATIENT CONCERNS: A 60-year-old
      woman presented with dyspnea and bilateral flank pain. The patient had no
      previous history of malignancy. DIAGNOSES: A contrast-enhanced chest computed
      tomography scan revealed a left breast mass and infiltrative soft tissue masses
      in the mediastinum and retroperitoneum, which showed high fluorodeoxyglucose
      uptake on positron emission tomography scan. The left breast mass was proven as a
      malignancy on biopsy and surgical excisional biopsy of the mediastinal mass
      revealed metastasis from the breast cancer on histopathologic examination.
      INTERVENTIONS: Our patient was treated with palliative hormone therapy for the
      primary breast cancer and metastasis with mediastinal and retroperitoneal
      fibrosis. OUTCOMES: Follow-up imaging studies showed improvement of the primary
      breast cancer and also metastasis. LESSONS: We report this rare case to emphasize
      that mediastinal and retroperitoneal fibrosis can be a presentation of metastasis
      from various primary malignancies. We expect that appropriate diagnosis and
      treatment for metastatic mediastinal and retroperitoneal fibrosis can have a
      beneficial effect on disease course and prognosis of the patient.

PMID- 30095662
TI  - The midterm outcomes of 1-stage versus 3-stage laparoscopic-assisted
      anorectoplasty in anorectal malformations with rectoprostatic fistula and
      rectobulbar fistula: A retrospective cohort study.
AB  - The aim of this study was to compare the midterm outcomes of 1-stage and 3-stage
      surgical procedures to treat anorectal malformations (ARMs) with rectoprostatic
      and rectobulbar fistula using laparoscopic-assisted anorectoplasty (LAARP).A
      total of 56 patients with ARMs and rectoprostatic and rectobulbar fistula who
      underwent LAARP from January 2011 to May 2014 in our institution were included in
      the study. They were divided into 2 groups according to the stage of procedure.
      The patients' data and postoperative complications were compared between the 2
      groups. The Krickenbeck classification was used for assessing the bowel
      functions.About 20 ARM newborns (rectoprostatic fistula [12], rectobulbar fistula
      [8]) successfully underwent a 1-stage LAARP, and about 36 ARM children
      (rectoprostatic fistula [20], rectobulbar fistula [16]) underwent a 3-stage LAARP
      (colostomy, LAARP, and closure of colostomy). The average age at the LAARP
      procedure in 1-stage group was significantly lower than that in 3-stage group
      (39.8 +/- 8.1 hours vs 4.9 +/- 1.2 months; P = .00). The average operative time
      during the definitive procedure was 132.2 +/- 15.9 minutes in the 1-stage group
      and 120.5 +/- 12.7 minutes in the 3-stage group (P = .13). There was only 5 to 10
      mL of blood loss during the LAARP procedure both the groups (P = .75). There were
      no significant differences between the 2 groups in postoperative hospital stay
      during the definitive procedure (10.2 +/- 2.3 days vs 8.5 +/- 2.2 days; P = .22).
      The rate of surgical site infection and dehiscence was 5% (1/20) in the 1-stage
      group and 5.6% (2/36) in 3-stage group (P = 1.00). During the period of follow
      up, the rate of voluntary bowel movement was 90% (18/20) in 1-stage group and
      94.4% (34/36) in 3-stage group (P = .94). Free from soiling or grade I soiling
      was 80% (16/20) in 1-stage group and 83.3% (30/36) in 3-stage group (P = 1.00);
      grade II soiling was found in 3 (10%) patients in 1-stage group and 85.7% in 3
      stage group (P = .75); grade III soiling was found in 3 (10%) patients in 1-stage
      group and 85.7% in 3-stage group (P = 1.00). Three patients (15%) in 1-stage
      group and 5 patients (13.9%) in 3-stage group suffered from grade I constipation
      (P = 1.00); while 3 (15%) patients in 1-stage group and 4 patients (11.1%) in 3
      stage group had grade II constipation (P = 1.00); no patients in the 2 groups
      suffered from grade III constipation.The 1-stage LAARP procedure for neonate with
      rectoprostatic and rectobulbar fistula can achieve comparable midterm outcomes as
      the conventional 3-stage LAARP procedure. It provides an alternative method to
      rectify the ARMs with rectoprostatic fistula and rectobulbar fistula without
      colostomy.

PMID- 30095663
TI  - Association between XRCC1 single-nucleotide polymorphisms and susceptibility to
      nasopharyngeal carcinoma: An update meta-analysis.
AB  - BACKGROUND: Many studies have investigated polymorphisms of X-ray repair cross
      complementing protein 1 (XRCC1) and risk of nasopharyngeal carcinoma (NPC), but
      the results are somewhat contradictory in different studies. There is an urgent
      need to keep in step with the relevant observational studies to more comprehend
      the effects of XRCC1 variants on the NPC risk. METHODS: A systematic literature
      search accompanied with meta-analysis was carried out to obtain a detailed
      evaluation on the association between XRCC1 polymorphisms and NPC risk. RESULTS:
      Meta-analyses showed that there was no statistically significant association
      observed between Arg194Trp/Arg280His variants in the XRCC1 gene and NPC risk with
      all genetic models, when relatively larger samples were pooled into the update
      meta-analysis. The reassessment suggested NPC risk was significantly increased
      with Arg399Gln polymorphism. The significant association was identified in
      homozygous, recessive, and allelic models, more than previously reported.
      CONCLUSION: We confirmed that Arg399Gln polymorphism of XRCC1 gene is a potential
      predictor for susceptibility to NPC, especially for Asians. More studies are
      required to evaluate the association in different populations.

PMID- 30095664
TI  - Clinical adverse effects of sodium-glucose cotransporter 2 inhibitors: Protocol
      for a systematic review and meta-analysis.
AB  - BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class
      of oral antidiabetic drugs, which mainly increase urinary glucose excretion
      through reducing renal glucose reabsorption. There is still a concern about the
      overall safety profile of SGLT2 inhibitors. In this systematic review and meta
      analysis, we will assess the clinical adverse effects of SGLT2 inhibitors in type
      2 diabetes mellitus. METHODS: This systemic review and meta-analysis described in
      this protocol will be conducted to follow the Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses guideline. We will search Medline, EMbase,
      the Cochrane library and the ClinicalTrials.gov Website from 1946 to June 2018.
      Studies will be screened by title, abstract, and full text independently in
      duplicate. Double-blinded, placebo-controlled, and randomized controlled trials
      reporting safety data of SGLT2 inhibitors will be eligible for inclusion.
      Outcomes will include adverse events (AEs) varying degrees and AEs occurring in
      >=3% patients or AEs aroused concerns by the Food and Drug Administration (FDA).
      The assessment of risk bias and data synthesis will be performed using STATA
      software (version12, Statacorp, College Station, TX). Outcomes will be reported
      by risk ratios for dichotomous outcomes and weighted mean difference (WMD) for
      continuous outcomes and their 95% confidence intervals. Subgroup, sensitivity,
      regression analyses will be performed to evaluate intertrial heterogeneity and
      bias of the results. I statistic will be used to evaluate heterogeneity among
      studies. RESULTS: This systemic review and meta-analysis will evaluate AEs
      occurring in >=3% patients or AEs aroused concerns by the FDA of SGLT2i as
      compared to placebo. CONCLUSION: Our study will provide a comprehensive picture
      of AEs of SGLT2 inhibitors.

PMID- 30095666
TI  - Dengue fever-associated necrotizing scleritis: A case report with long-term
      follow-up.
AB  - RATIONALE: Dengue fever is a notable emerging infectious disease that is now seen
      worldwide, with an estimated incidence of approximately 390 million cases per
      year. Although ocular complications are uncommon among dengue fever-infected
      patients, caution is needed to prevent vision loss. Here we report a potentially
      serious sight-threatening complication of dengue fever, dengue fever-associated
      necrotizing scleritis. PATIENT CONCERNS AND DIAGNOSIS: After being bitten by
      mosquitoes, a 60-year-old Japanese female exhibited positive serologic tests of
      immunoglobulin M and G enzyme immunoassays for dengue viral infection along with
      a decrease of leukocytes and platelets. These findings led to a dengue fever
      diagnosis. Slit lamp examination of her left eye revealed a conjunctival and
      scleral injection, elevation of the entire circumference of the sclera, and
      bulging of the sclera on the nasal upper side with a patch of avascular
      episcleral tissue. Since additional systemic examinations identified no
      autoimmune diseases such as rheumatism, we diagnosed the patient as dengue fever
      associated scleritis. INTERVENTIONS: Intensive systemic and topical steroids were
      administrated during the initial acute phase. Over the next 15 months, the amount
      of steroid was tapered off. OUTCOME: Initial findings for the scleritis gradually
      declined in response to steroid treatment. Although there was no recurrence of
      active scleritis, gradual thinning of the sclera continued to occur during the 18
      year follow-up. LESSONS: To the best of our knowledge, this is the first reported
      case of dengue fever-associated necrotizing scleritis with long-term follow-up.
      This case suggests the existence of a long-term immune-mediated mechanism during
      the development of the dengue fever-associated necrotizing scleritis. Dengue
      fever virus patients found to have red eyes need to be carefully followed and
      treated, as these eyes might develop thinning of the sclera that could lead to
      rupture of the globe, thereby resulting in blindness.

PMID- 30095667
TI  - CD133 expression correlates with clinicopathologic features and poor prognosis of
      colorectal cancer patients: An updated meta-analysis of 37 studies: Erratum.

PMID- 30095665
TI  - Effect of 2% lidocaine continuous epidural infusion for thoracic or lumbar herpes
      zoster-related pain.
AB  - Few treatments are effective to manage herpes-zoster (HZ)-related pain. This
      retrospective study focused on the efficacy of 2% lidocaine continuous epidural
      infusion on pain control and quality of life in patients with thoracic or lumbar
      HZ.A total of 256 patients with thoracic or lumbar HZ were reviewed for this
      study. Patients included in the study were divided into continuous epidural
      infusion (70 mL 2% lidocaine + 180 mL 0.9% normal saline) and medical therapy
      group (group1) and only medical therapy group (group2). European Organization for
      Research and Treatment of Cancer and Izbicki pain score were used to evaluate the
      pain control and quality of life before therapy, and 6 and 9 months after
      therapy.For 256 patients with HZ (thoracic HZ = 162, lumbar HZ = 94), 53.1% was
      women. Mean +/- standard deviation age was 69.4 +/- 9.5 ( range, 38-85) years.
      Significant differences between the 2 groups in terms of quality of life and pain
      control were detected after 6 and 9 months follow-up (P < .001). For patients
      with HZ at 1 to 3 months after rash onset, the pain score was significantly lower
      in group 1 (P < .001). Sixteen patients with postherpetic neuralgia (PHN)
      underwent continuous epidural infusion therapy. Only 4 patients achieved
      satisfactory pain relief. Seven patients required analgesic drugs, and 6 patients
      still were unable to work, 10/16 (62.5%) patients had readmission. In addition,
      the pain score was higher in patients with HZ with diabetes (P < .001). Epidural
      infection occurred in 6 patients (8.8%), catheter dislodgement in 4 patients
      (5.8%), and catheter leakage in 3 patients (4.4%). There was no spinal epidural
      abscesses occurred.2% lidocaine continuous epidural infusion therapy can lead to
      sustained pain relief and improve the quality of life in patients with for
      thoracic or lumbar HZ at 1 to 3 months after rash onset. Epidural lidocaine is
      avoided for the treatment PHN, and the level of glucose might be associated with
      zoster-related pain.

PMID- 30095668
TI  - Gender dysphoria in youth: An overview for primary care providers.
AB  - BACKGROUND AND PURPOSE: Primary care providers who encounter children are often
      the first line of contact for individuals with gender dysphoria, which occurs
      when sex assigned at birth is incongruent with one's true, expressed sexual
      identity. Because those with untreated gender dysphoria are at risk of a variety
      of negative outcomes, including mood symptomatology, suicidality, substance use
      disorders, and other psychosocial risk factors, it is critical that health care
      providers are adept in the provision of holistic, patient-centered care. The
      purpose of this report is to provide an updated review of the current evidence
      from the literature pertaining to the identification, treatment, and coordination
      of care among children with gender dysphoria within the primary care setting or
      medical home. METHODS: Using PubMed and CINAHL, a literature review spanning from
      2012 to the present was conducted using the following key words: gender
      dysphoria, transgender health, LGBT health, and hormone therapy. Reference lists
      of identified articles were also explored for relevance. CONCLUSIONS: Treatment
      may include a social transition, hormone antagonist therapy, or the
      administration of cross-sex hormone therapy, with a medical home needed to
      facilitate coordination of care. Best practice guidelines vary across pediatric
      and developmental groups and include both reversible and nonreversible
      modalities. Screening for negative psychosocial sequelae must be completed to
      include mood symptomatology, suicidality, substance use disorders, and risky
      sexual behavior, so that appropriate screening, identification, and treatment
      interventions can be implemented. IMPLICATIONS FOR PRACTICE: The primary care
      medical home must act as a foundation for the identification of gender dysphoria
      and/or associated comorbidities and must treat, when able, or refer, when
      indicated. In addition, because of structural barriers and stigmatization, public
      policy often fails the transgender community and can exacerbate the
      aforementioned psychosocial comorbidities faced by the transgender youth
      community. Health care providers, particularly nurse practitioners, are in a
      unique position to expand on the face-to-face care provided to the community and
      engage in advocacy efforts to dismantle structural barriers impeding transgender
      individuals and communities while also providing primary health care,
      anticipatory guidance, and care coordination.

PMID- 30095669
TI  - Effectiveness of early identification and electronic interventions for teens with
      risk factors for the development of heart disease and diabetes: Phase II
      findings.
AB  - BACKGROUND AND PURPOSE: Serum and physical risk factors for the development of
      heart disease and diabetes are detectable long before adulthood. The purpose of
      this two-part study was to assess the prevalence and associations of these risk
      factors in teens and determine the effectiveness of a customizable two-part
      electronic education program on minimizing identified risks. METHODS: Data were
      collected from teens (n = 168) from two high schools (one urban and one rural) in
      the mid-Atlantic region. After baseline data were collected, the two-part
      electronic education program was initiated. Serum and physical risk factors were
      rechecked at 12-week intervals, and results were analyzed. CONCLUSIONS:
      Significant serum and physical risk factor associations were identified and
      remained present among teens over the course of the study. High-density
      lipoproteins showed significant, steady improvement. Low-density lipoproteins
      were positively associated with body mass index, diastolic blood pressure, and
      thyroid-stimulating hormone level. IMPLICATIONS FOR PRACTICE: Although serum and
      physical risk factors are identifiable in teens, routine screening of this age
      group and younger is not an established standard of care. Health care providers
      need effective, innovative methods to counteract these risks. Through increased
      awareness of the presence of risk factors in young patients, advanced nurse
      practitioners may implement earlier interventions to counteract these risks.

PMID- 30095670
TI  - Comparing nurse practitioners/physician assistants and physicians in diagnosing
      adult abdominal pain in the emergency department.
AB  - BACKGROUND AND PURPOSE: This retrospective study compared nurse practitioners and
      physician assistants (NPs/PAs) with physicians on their assignment of Emergency
      Severity Index level 3 (ESI level 3) acute abdominal pain (AAP) in the emergency
      department (ED). METHODS: Data obtained from a large ED group staffing four
      hospitals yielded 12,440 de-identified, adult patients diagnosed on ED admission
      with AAP ESI level 3 for descriptive analysis with logistic regression.
      CONCLUSIONS: Results revealed that the comparison of ESI level 3 AAP diagnoses
      was consistent between admission and discharge 95.3% for physicians, 92.9% for
      NPs/PAs, and 97.1% for NP/PA and physician collaboration (chi = 46.01, p < .001).
      Logistic regression suggested that NP/PA had significantly reduced odds (31%) of
      consistent admitting/discharge diagnoses, whereas collaboration of NP/PA with
      physicians had significantly increased odds of consistent diagnosis (41%)
      compared with physicians alone. Two hospitals with similar distributions of
      NPs/PAs and physicians exhibited greater odds of consistent diagnoses over
      hospitals with disproportionate distributions; a secondary finding worth
      exploring. Consistent AAP ESI level 3 diagnoses by outcomes were admissions
      (>99%), discharges (94%), and left against medical advice/transferred (98%; chi =
      102.94, p < .001). IMPLICATIONS FOR PRACTICE: The highest percentage of
      consistent AAP ESI level 3 diagnoses between ED admission and discharge was when
      NPs/PAs and physicians collaborated.

PMID- 30095671
TI  - Integrating oral health curricula into nurse practitioner graduate programs:
      Results of a US survey.
AB  - BACKGROUND AND PURPOSE: Nurse practitioners (NPs) are a significant segment of
      the US primary care workforce and have a pivotal role in improving access to oral
      health (OH) care. The purpose of this research was to assess OH curricular
      integration in primary care NP programs and to examine factors that influence
      integration and satisfaction with graduates' level of OH competence. METHODS: A
      cross-sectional, national survey of NP programs (N = 466) was conducted using an
      electronically distributed 19-item, self-administered questionnaire. Data
      analysis included univariate, bivariate, multivariate statistics, and logistic
      regression modeling. CONCLUSIONS: The large majority of pediatric, family, and
      adult-gerontology primary care programs are educating NP graduates about OH.
      Significant factors promoting integration and satisfaction with graduates' level
      of competence included the presence of a faculty champion and routine teaching by
      a dental professional or nondental OH expert. IMPLICATIONS FOR PRACTICE: With
      adequate OH education, NPs are ideally positioned to integrate OH and primary
      care services in practice, thereby, improving access to OH care.

PMID- 30095673
TI  - When Family Matters Most: A Test of the Association Between Sexual Minority
      Identity Disclosure Context and Diurnal Cortisol in Sexual Minority Young Adults.
AB  - OBJECTIVE: Revealing one's sexual identity to others is a complex process marked
      by a shift in the types of stressors faced by sexual minority young adults. Such
      stressors influence the secretion of health-relevant hormones, including
      cortisol, yet how dimensions of disclosure (i.e., the degree and context)
      influence neuroendocrine functioning remains poorly understood. The current study
      examined the association between disclosure context (disclosure to family
      members, friends/co-workers/acquaintances, and members of religious groups) and
      diurnal cortisol while allowing disclosure to vary in degree (i.e., how much is
      disclosed). METHODS: One hundred twenty-one sexual minority young adults (aged 18
      35 years, 54.5% female, free of major psychiatric/endocrine disorders) completed
      an initial survey that assessed the degree and context of sexual minority
      identity disclosure. A randomly selected subset (n = 58) also provided salivary
      cortisol samples at wake, 45 minutes after wake, 12 hours after wake, and at
      bedtime for 1 week. RESULTS: Greater total disclosure and greater disclosure to
      family members were associated with reduced cortisol output, defined as Area
      Under the Curve relative to ground (AUCg; F(1,230) = 5.95, p = .015, and F(1,231)
      = 10.90, p = .001, respectively). Disclosure to co-workers, friends,
      acquaintances, or religious groups was unrelated to cortisol AUCg. All disclosure
      contexts tested were unrelated to the shape of diurnal cortisol slopes (including
      the cortisol awakening response). CONCLUSIONS: Disclosure to family members
      uniquely predicted cortisol AUCg. Therefore, these results suggest that effects
      of disclosure on diurnal cortisol and its associated health outcomes may occur in
      the context of familial relationships.

PMID- 30095672
TI  - A Microbial Signature of Psychological Distress in Irritable Bowel Syndrome.
AB  - OBJECTIVE: Irritable bowel syndrome (IBS) is associated with alterations along
      the brain-gut-microbiota axis. Previous studies have suggested a parallel
      segregation of microbial features and psychological burden in IBS. This study
      aimed at exploring the microbial correlates of psychological distress in patients
      with IBS. METHODS: Forty-eight patients with IBS (Rome III criteria, M (SD) age =
      42 (15) years, 35 female, 25 diarrhea-dominant, 5 constipation-dominant, and 18
      alternating-type IBS) were assessed for psychological and clinical variables with
      validated questionnaires, fecal samples underwent microbial 16S rRNA analyses
      (regions V1-2). Microbial analyses comprised examination of alpha and beta
      diversity, correlational analyses of bacterial abundance and comparisons among
      subgroups defined by thresholds of psychological and IBS symptom variables, and
      machine learning to identify bacterial patterns corresponding with psychological
      distress. RESULTS: Thirty-one patients (65%) showed elevated psychological
      distress, 22 (31%) anxiety, and 10 depression (21%). Microbial beta diversity was
      significantly associated with distress and depression (q = .036 each, q values
      are p values false discovery rate-corrected for multiple testing). Depression was
      negatively associated with Lachnospiraceae abundance (Spearman's rho = -0.58, q =
      .018). Patients exceeding thresholds of distress, anxiety, depression, and stress
      perception showed significantly higher abundances of Proteobacteria (q = .020
      .036). Patients with anxiety were characterized by elevated Bacteroidaceae (q =
      .036). A signature of 148 unclassified species accounting for 3.9% of total
      bacterial abundance co-varied systematically with the presence of psychological
      distress. CONCLUSIONS: Psychological variables significantly segregated gut
      microbial features, underscoring the role of brain-gut-microbiota interaction in
      IBS. A microbial signature corresponding with psychological distress was
      identified. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier
      NCT02536131, retrospectively registered.

PMID- 30095674
TI  - Anterior Pelvic Ring: Introduction to Evaluation and Management.
AB  - The evaluation and management of pelvic ring injuries continues to evolve.
      Historic treatment was primarily nonsurgical, which yielded to open surgical
      treatment as the benefits of restoring pelvic anatomy and stability became clear.
      The development of percutaneous techniques for pelvic ring fixation enabled
      surgeons to reduce and stabilize certain injuries without the need for large open
      surgical dissections. Although percutaneous iliosacral screw fixation of sacral
      fractures and sacroiliac disruptions is the standard for most posterior pelvic
      ring injuries, the evaluation and treatment of anterior pelvic ring disruptions
      remains a controversial topic among surgeons who treat these injuries.
      Universally accepted indications for anterior pelvic ring stabilization do not
      exist, and there is little comparative data to support one surgical technique
      over another. In fact, some believe that for many injuries, the anterior ring
      rarely requires fixation after stable fixation of the posterior pelvic ring. The
      purpose of this work is to present a brief history on management of the anterior
      pelvic ring as a component of pelvic ring disruptions and briefly review the
      anatomy of the anterior pelvic ring. Finally, we will introduce the current
      techniques available for anterior pelvic reduction/stabilization and present
      information on evaluation of anterior ring stability as a means of guiding
      treatment.

PMID- 30095676
TI  - The Use of External Fixation for the Management of the Unstable Anterior Pelvic
      Ring.
AB  - The objective of this article was to highlight the indications and various
      methods of external fixation for management of the unstable anterior pelvic ring.
      Although most often used temporarily in the setting of significant hemorrhage
      from a pelvic ring fracture, external fixation remains an option for definitive
      stabilization of select pelvic ring injuries. Classically, the iliac crest frame
      has been used, although use of the supra-acetabular frame has gained favor due to
      its superior bone purchase and improved biomechanics. Common complications from
      external fixation include pin site infections, loss of reduction, and the
      "external fixator deformity."

PMID- 30095675
TI  - Intramedullary Fixation Techniques for the Anterior Pelvic Ring.
AB  - The superior ramus is an irregularly shaped, undulating, and curvilinear osseous
      structure that can provide an osseous conduit for intramedullary screws. A wide
      spectrum of variability between the curve and obliquity of the superior ramus
      osseous fixation pathway (OFP) exists in both the anteroposterior and the coronal
      planes. A detailed understanding of the osseous topography and how it correlates
      with fluoroscopic imaging is mandatory. Obtaining the correct intraoperative
      inlet and combined obturator oblique-outlet fluoroscopic views specific to each
      patient's anatomy is necessary for safe implant insertion. Intramedullary screws
      can be inserted in either an antegrade or a retrograde direction depending on a
      number of variables, including fracture location, the proximity of patient's
      external genitalia to the skin insertion side, and the possible impact of thigh
      girth on the surgeons hand position. Multiple screw insertion techniques are
      possible, but a simple and reproducible technique is described. The size and
      number of screws that can be inserted is variable, differs between surgeons, but
      is ultimately dependent on the cortical limits of the superior ramus OFP.
      Standard screw insertion techniques are successful in most patients. If the
      osseous corridor or external anatomy impedes standard insertional techniques,
      several modifications exist that can allow successful screw insertion. A thorough
      understanding of each patient's anatomy, injury, and precise surgical technique
      with the appropriate fluoroscopic views are required to safely place intraosseous
      intramedullary implants into the superior ramus OFP.

PMID- 30095677
TI  - Indications for Open Reduction Internal Fixation of Anterior Pelvic Ring
      Disruptions.
AB  - In acute trauma, pelvic ring instability can lead to hemorrhage and hemodynamic
      instability. Pelvic ring instability and displacement that is not stabilized may
      lead to chronic pain, sitting imbalance, and limb length inequality. Methods and
      timing of securing anterior pelvic ring injuries operatively is controversial and
      debatable. Many orthopaedic trauma surgeons would agree that acceptable methods
      to treat a disrupted anterior pelvic ring fracture include nonoperative care,
      external fixation, internal spanning fixators, intramedullary superior ramus
      screws, and open reduction internal fixation. We will review the indications for
      open reduction internal fixation fractures and disruptions of the anterior pelvic
      ring.

PMID- 30095678
TI  - Anterior Subcutaneous Internal Pelvic Fixation/INFIX: A Systemic Review.
AB  - INTRODUCTION: The purpose of this article is to review the available literature
      on anterior subcutaneous internal pelvic fixation (ASIPF) to identify
      indications, clinical and radiographic outcomes, and compare these with
      alternative fixation methods. METHODS: Using the Preferred Reporting Items for
      Systematic Reviews and Meta-analyses guidelines, a systematic search on PubMed
      and Google Scholar was performed. Articles included were in the English language
      or English translations and published between 2007 and 2018. Studies included
      were appraised with narrative data synthesis. RESULTS: Twenty-five articles with
      496 patients were included. These included 17 case series, with 3 case reports
      reporting adverse events. CONCLUSIONS: ASIPF and the appropriate posterior
      fixation resulted in healing of pelvic ring injuries in 99.5% of cases.
      Indications include unstable pelvic ring injuries with the appropriate posterior
      fixation. Radiographic parameters and outcome measures were infrequently
      reported. ASIPF is a valuable tool for reduction and fixation in unstable pelvic
      ring injuries. Complications include lateral femoral cutaneous nerve irritation
      (26.3%); heterotopic ossification (36%); infection (3%); and femoral nerve palsy
      (1%), which is likely related to placing the bar and screws too deep.

PMID- 30095679
TI  - Effect of Deformity and Malunion of the Anterior Pelvic Ring.
AB  - Pelvic fractures are common after high-energy trauma and are often associated
      with ligamentous injury. Treatment is guided by assessing stability of the pelvic
      ring, and unstable injuries frequently require surgery to achieve a desirable
      outcome. Assessment of pelvic ring stability is often possible with physical
      examination and standard imaging studies (plain radiographs and computed
      tomography); however, these "static" imaging modalities may not adequately
      identify dynamically unstable pelvic injuries that require surgery. Cadaveric and
      clinical data suggest that the injured pelvis may recoil significantly from the
      point of maximal displacement, and some unstable injuries may not be recognized
      until patients present with clinical symptoms. This article presents the case of
      a patient who sustained a minimally displaced pelvic ring injury that was stable
      on bedside examination and static imaging, but ultimately was unstable. She
      developed a substantial pelvic malunion with significant pain and activity
      limitations. The patient subsequently underwent successful pelvic ring
      reconstruction, and she remains asymptomatic at 2 years.

PMID- 30095680
TI  - Physics of Transcranial Direct Current Stimulation Devices and Their History.
AB  - Transcranial direct current stimulation (tDCS) devices apply direct current
      through electrodes on the scalp with the intention to modulate brain function for
      experimental or clinical purposes. All tDCS devices include a current controlled
      stimulator, electrodes that include a disposable electrolyte, and headgear to
      position the electrodes on the scalp. Transcranial direct current stimulation
      dose can be defined by the size and position of electrodes and the duration and
      intensity of current applied across electrodes. Electrode design and preparation
      are important for reproducibility and tolerability. High-definition tDCS uses
      smaller electrodes that can be arranged in arrays to optimize brain current flow.
      When intended to be used at home, tDCS devices require specific device design
      considerations. Computational models of current flow have been validated and
      support optimization and hypothesis testing. Consensus on the safety and
      tolerability of tDCS is protocol specific, but medical-grade tDCS devices
      minimize risk.

PMID- 30095681
TI  - tDCS in Addiction and Impulse Control Disorders.
AB  - The study of addiction and impulsion control disorders has shown that behaviors
      of seeking and consumption of addictive substances are subserved by
      neurobiological alterations specifically related to brain networks for reward,
      stress, and executive control, representing the brain's adaptation to the
      continued use of an addictive substance. In parallel, studies using
      neuromodulation techniques such as transcranial direct current stimulation (tDCS)
      have demonstrated promising effects in modulating cognitive and motor functions.
      This review aims to describe the neurobiology of addiction and some of the most
      relevant cognitive models of addictive behavior and to clarify how tDCS
      application modulates the intake and craving for several addictive substances,
      such as food, alcohol, nicotine, cocaine, crack, methamphetamine, and cannabis.
      We also discuss the positive and null outcomes of the use of this neuromodulatory
      technique in the treatment of addiction disorders resulting from the use of these
      substances. The reviewed findings lead us to conclude that tDCS interventions
      hold several promising clinical avenues in addiction and impulsive control.
      However, methodological investigations are necessary for undercover optimal
      parameters before implementing its clinical application.

PMID- 30095682
TI  - Special Issue on Transcranial Direct Current Stimulation.

PMID- 30095683
TI  - Transcranial Direct Current Stimulation in Neurodegenerative Disorders.
AB  - Cortical excitability modulation and neuroplasticity are considered essential
      mechanisms for improving clinical and cognitive abilities in neurodegenerative
      disorders (NDDs). In such context, transcranial direct current stimulation (tDCS)
      shows great promise for facilitating remodeling of neurosynaptic organization.
      The aim of this review was to provide an overview of how tDCS is currently used
      as a neurorehabilitation strategy in some NDDs. We describe results from studies
      in which tDCS was applied in mild cognitive impairment, Alzheimer's disease, and
      primary progressive aphasia. Currently, findings related to the ability of tDCS
      to restore cognitive dysfunctions and behavioral impairments in these NDDs do not
      seem to support the notion that tDCS shows clear therapeutic efficacy in patients
      with mild cognitive impairment, Alzheimer disease, and primary progressive
      aphasia. This is probably because tDCS research in this area is still in its
      early stages. Methodological concerns, such as differences in tDCS parameters
      (eg, intensity or duration), target sites, and study design (eg, the relationship
      between tDCS and the rehabilitation strategy), or the use of underpowered sample
      sizes may also contribute to these outcomes. Nevertheless, it is important to
      note that almost no studies have evaluated how the underlying neurophysiological
      state of patients should guide the application of tDCS. These results should not
      prevent the use of tDCS in these NDDs, but they should trigger a deeper
      evaluation of how tDCS should be used. Transcranial direct current stimulation
      cannot be considered a neurorehabilitation apparatus by itself but should be
      instead viewed as a method for weakly modulating existing brain excitability.
      Future studies should aim to improve our understanding of the neurophysiological
      mechanisms that underlie the clinical effects of tDCS with the final goal of
      designing and performing individualized stimulation protocols that can be
      tailored for each NDD patient and combined with other appropriate
      neurorehabilitation strategies.

PMID- 30095684
TI  - Transcranial Direct Current Stimulation in Obsessive-Compulsive Disorder,
      Posttraumatic Stress Disorder, and Anxiety Disorders.
AB  - Obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and
      anxiety disorders share the basic clinical feature of anxiety, which probably
      explains their common response to similar pharmacological and psychological
      interventions. Transcranial direct current stimulation (tDCS) is a
      neuromodulation technique that has proved effective in reducing the symptoms of a
      number of neuropsychiatric disorders. It was also used in healthy subjects to
      modulate neuropsychological processes that are involved in the pathophysiology of
      anxiety. We review the published studies in which tDCS was administered to
      patients with OCD, PTSD, or anxiety disorders. Our systematic search in the major
      electronic databases resulted in 14 articles for OCD, 1 for an OCD-related
      disorder (ie, hoarding disorder), 2 for PTSD, and 2 for anxiety disorders. In the
      studies involving OCD patients, tDCS was targeted to either the dorsolateral
      prefrontal cortex or the orbitofrontal cortex or the pre-supplementary motor area
      and induced a clear reduction of obsessive-compulsive symptoms. However, the lack
      of sham control groups and the great diversity in sample selection and tDCS
      protocols among studies prevent us from generalizing these results. In the
      studies involving PTSD and anxiety disorders patients, tDCS was applied over the
      dorsolateral prefrontal cortex and reduced symptoms, but the number of treated
      patients is too little to draw any conclusion on efficacy. However, these reports
      highlighted the importance of combining tDCS with different procedures, including
      computerized tasks and behavioral paradigms. In conclusion, even in its infancy,
      the use of tDCS for the treatment of OCD, PTSD, and anxiety disorders does show
      promise and deserves extensive research effort.

PMID- 30095685
TI  - Cognitive Effects of Transcranial Direct Current Stimulation in Healthy and
      Clinical Populations: An Overview.
AB  - Transcranial direct current stimulation (tDCS) is a neuromodulatory approach that
      is affordable, safe, and well tolerated. This review article summarizes the
      research and clinically relevant findings from meta-analyses and studies
      investigating the cognitive effects of tDCS in healthy and clinical populations.
      We recapitulate findings from recent studies where cognitive performance paired
      with tDCS was compared with performance under placebo (sham stimulation) in
      single sessions and longitudinal designs where cognitive effects were evaluated
      following repeated sessions. In summary, the tDCS literature currently indicates
      that the effects of tDCS on cognitive measures are less robust and less
      predictable compared with the more consistent effects on motor outcomes. There is
      also a notable difference in the consistency of single-session and longitudinal
      designs. In single-session tDCS designs, there are small effects amid high
      variability confounded by individual differences and potential sham stimulation
      effects. In contrast, longitudinal studies provide more consistent benefits in
      healthy and clinical populations, particularly when tDCS is paired with a
      concurrent task. Yet, these studies are few in number, thereby impeding design
      optimization. While there is good evidence that tDCS can modulate cognitive
      functioning and potentially produce longer-term benefits, a major challenge to
      widespread translation of tDCS is the absence of a complete mechanistic account
      for observed effects. Significant future work is needed to identify a priori
      responders from nonresponders for every cognitive task and tDCS protocol.

PMID- 30095686
TI  - Enhancing and Advancing Shared Governance Through a Targeted Decision-Making
      Redesign.
AB  - OBJECTIVE: The study aim was to determine if a targeted redesign of shared
      decision making improved shared governance (SG). BACKGROUND: Nursing SG is
      collaborative decision making between nurses at every level; it improves quality
      of care, empowers nurses, and enhances nurse satisfaction. METHODS: Using a quasi
      experimental, pretest/posttest design, researchers electronically distributed the
      Index of Professional Nursing Governance (IPNG) to an inclusive, convenience
      sample of RNs in a Magnet(r)-designated 377-bed community medical center.
      Preintervention scores were used to tailor a redesign of shared decision making,
      and postintervention data were collected within 1 year to measure outcomes.
      RESULTS: IPNG overall score and 5 of 6 subscale scores significantly increased
      after the redesign. CONCLUSIONS: Changes to an SG structure can take 2 to 5 years
      to be realized. Our findings corroborate that the IPNG is a valuable tool in
      promoting setting-specific SG.

PMID- 30095688
TI  - Radiation dose reduction in myocardial perfusion imaging single-photon emission
      computed tomography/computed tomography using a dose-tracking software.
AB  - OBJECTIVE: We describe our experience with a dose-tracking software (Radimetrics)
      that was used to optimize, from a dosimetric point of view, the single-photon
      emission computed tomography/computed tomography protocols used in myocardial
      perfusion imaging. PATIENTS AND METHODS: We extracted and assessed the major
      dosimetric indices as the administered activity, the computed tomography dose
      index, the dose length product and the size-specific dose estimates for a large
      sample of patients before and after an optimization process. We also evaluated
      both the effective and the equivalent dose to organs for all the procedures.
      RESULTS: We achieved a reduction in administered activity by 17.8 and 4.5% for 2-
      and 1-day protocols, respectively; moreover size-specific dose estimates related
      to a single computed tomography acquisition was reduced by 50%. The organs that
      received the highest equivalent dose were the heart and the breast, and with the
      new protocols, these values were almost halved.The average single-photon emission
      computed tomography/computed tomography myocardial perfusion imaging effective
      dose decreased from 21.9+/-2.5 to 15.6+/-1.4 mSv for the 2-day protocol and from
      17.8+/-1.7 to 13.6+/-1.5 mSv for the 1-day protocol. This meant that with a
      simple but targeted action on acquisition protocols, it was possible to achieve
      considerable dosimetric reduction.The adoption of a dose-tracking software
      represented an easy approach to optimization. Furthermore, we could easily
      calculate the main dosimetric indices and check their trends day by day to
      perform the necessary corrective actions in real timeVideo abstract:
      http://links.lww.com/NMC/A135.

PMID- 30095687
TI  - Relationship of Staff Information Sharing and Advice Networks to Patient Safety
      Outcomes.
AB  - OBJECTIVE: The aim of this study was to compare information sharing and advice
      networks' relationships with patient safety outcomes. BACKGROUND: Communication
      contributes to medical errors, but rarely is it clear what elements of
      communication are key. METHODS: We investigated relationships of information
      sharing and advice networks to patient safety outcomes in 24 patient care units
      from 3 hospitals over 7 months. Web-based questionnaires completed via Android
      tablets provided data to create 2 networks using ORA, a social network analysis
      application. Each hospital provided nurse-sensitive patient safety outcomes.
      RESULTS: In both networks, medication errors correlated positively with node
      count and average distance and negatively with clustering coefficient. Density
      and weighted density negatively correlated with medication errors and falls in
      both networks. Eigenvector and total degree centrality correlated negatively with
      both safety outcomes, whereas betweenness centrality positively related to falls
      in the information-sharing network. CONCLUSION: Technology-enabled social network
      analysis data collection is feasible and can provide managers actionable system
      level information.

PMID- 30095689
TI  - A Case of Allergic Broncopulmonary Aspergillosis Associated With Hematopoietic
      Stem Cell Transplantation Due to Chronic Granulomatous Disease.
AB  - Allergic bronchopulmonary aspergillosis is an immunologic pulmonary disorder
      caused by hypersensitivity to Aspergillus fumigatus. This disorder is most
      commonly seen in patients with poorly controlled asthma and cystic fibrosis. It
      is rarely reported in chronic granulomatous disease patients; however, there are
      no cases reported with hematopoietic stem cell transplantation in the English
      literature. Herein, we report a patient with chronic granulomatous disease who
      had hematopoietic stem cell transplantation and subsequently developed allergic
      bronchopulmonary aspergillosis.

PMID- 30095690
TI  - Cisplatin-induced Ototoxicity in Children With Solid Tumor.
AB  - Cisplatin is the principal chemotherapeutic agent and also tremendously increases
      the survival for pediatric patients with neuroblastoma or hepatoblastoma. With
      the extended overall survival period, clinical medical workers and parents
      gradually attach more attention to the late effect of chemotherapy of these
      children. The purpose of this study is to analyze the incidence and risk factors
      of cisplatin-based hearing loss. We retrospectively collected the archives of
      cisplatin-based chemotherapy and audiometric evaluation from 2005 through 2017 at
      Xinhua Hospital. From 384 patients treated with cisplatin, full data of 59
      patients were available, and 14 cases (23.7%) were identified as significant
      hearing loss. The median time from usage of platinum compounds to the most recent
      audio test was 406 days. Cumulative and single maximum cisplatin dose was 622.6+/
      283.2 and 137.6+/-51.6 mg/m/cycle, respectively. Accumulated cisplatin dose (95%
      confidence interval, 1.001-1.006; P=0.012) and single maximum cisplatin dose (95%
      confidence interval, 1.000-1.029; P=0.049) were independently important
      predictors for moderate to severe hearing loss in children treated with
      cisplatin. Cisplatin can cause ototoxicity which profoundly handicap language
      development and social communication for children. Regular audiological
      management and long-term follow-up are strongly recommended for this vulnerable
      group.

PMID- 30095691
TI  - Blood Stream Infections and Antibiotic Utilization in Pediatric Leukemia Patients
      With Febrile Neutropenia.
AB  - BACKGROUND: Frequent surveillance of bacterial pathogens responsible for
      microbiologically defined-blood stream infections (MD-BSI), and their respective
      antibiotic susceptibilities is central to tailoring empiric antibiotic therapy in
      febrile neutropenia (FN) episodes in pediatric patients with leukemia. The safety
      of deescalating antibiotic therapy in pediatric patients with leukemia and
      neutropenia is incompletely understood. METHODS: A retrospective chart review of
      194 FN episodes occurred between the years of 2013 and 2016 in 67 patients with
      leukemia. Clinical and microbiological data were recorded. RESULTS: MD-BSI
      occurred in 36 of 194 (18%) of FN episodes. Deescalation of empiric antibiotic
      therapy based on antibiotic susceptibilities was possible in 25 of 36 (69.4%)
      episodes. In those 25 episodes, where there was an opportunity to deescalate the
      antibiotic spectrum, it was clinically appropriate to do so in 19. Deescalation
      occurred in 9 (47.4%) of these episodes without complication. The remaining 10
      patients received a median of 20 additional days of broad-spectrum antibiotic
      therapy (range, 12 to 30 d). CONCLUSIONS: In our small cohort of patients,
      deescalation of antibiotic therapy based on antimicrobial susceptibilities did
      not result in complication. Larger prospective studies are needed to address the
      safety of deescalating antibiotic therapy in this population.

PMID- 30095692
TI  - Successful Use of EPOCH-R in 2 Young Adult Patients With Burkitt Lymphoma and
      Acute Kidney Injury: A Case Report.
AB  - Pediatric Burkitt lymphoma has historically been treated with intensive
      methotrexate-based chemotherapy, which improves patient survival while causing
      severe toxicities. Young patients typically have better outcomes with intensive
      therapies, while adults and immunocompromised patients have higher toxicities and
      worse outcomes. Newer treatment regimens, including etoposide, prednisone,
      vincristine, cyclophosphamide, doxorubicin, rituximab (EPOCH-R), show promise for
      these patients. However, few studies exist to demonstrate efficacy and improved
      toxicity profile with EPOCH-R. We present 2 cases: a 25-year-old male with Down
      syndrome and an 18-year-old male with Burkitt lymphoma and significant renal
      injury who were successfully treated with EPOCH-R with minimal toxicities.This is
      an open-access article distributed under the terms of the Creative Commons
      Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is
      permissible to download and share the work provided it is properly cited. The
      work cannot be changed in any way or used commercially without permission from
      the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 30095693
TI  - Childhood Head and Neck Lymphadenopathy: A Report by a Single Institution (2003
      2017).
AB  - Actually, there is still no consensus related to diagnostic and management
      algorithms in case of head and neck lymphadenopathy in children. The aim of our
      study was to analyze the causes of head and neck lymphadenopathy in children to
      determine a systematic diagnostic approach. We enrolled all cases of head and
      neck lymphadenopathy in children under the age of 18 diagnosed at the Unit of
      Hemato-Oncology, Pediatric Department of University "Luigi Vanvitelli," Naples,
      over a 15-year period (January 2003-December 2017). In total, 405 patients (271
      males) were enrolled in the study. Thirteen cases due to other causes, were left
      off the study. Therefore, the study was performed on 392 cases. A total of 220
      patients (56.1%) had a history of infection, 66 cases (16.8%) a diagnosis of
      neoplasia, and 101 (24.9%) cases a diagnosis of reactive inflammatory changes of
      nonspecific origin. We have observed the following from our study: (1) the acute
      infections are the most common causes of head and neck lymphadenopathy in the
      pediatric population; (2) in about a quarter of patients, the lymphadenopathy
      resulted by nonspecific origin; (3) the supraclavicular nodes should be regarded
      with a high index of suspicion of malignancy.

PMID- 30095694
TI  - Risk Markers for Significant Bleeding and Thrombosis in Pediatric Acute
      Promyelocytic Leukemia; Report From the Children's Oncology Group Study AAML0631.
AB  - Acute promyelocytic leukemia (APL) is characterized by a heightened risk of
      coagulopathy with significant morbidity and mortality. Here we report our
      evaluation of presenting white blood cell (WBC) and the International Society on
      Thrombosis and Haemostasis (ISTH) disseminated intravascular coagulation (DIC)
      scoring system as markers for early death and nonlethal coagulopathy in pediatric
      APL. We evaluated 79 pediatric patients treated on a Children's Oncology Group
      phase III clinical trial. There were 4 early deaths and 13 nonlethal, clinically
      significant (grade III to IV) coagulopathy events during induction. Elevated
      presenting WBC was significantly associated with early death but not with both
      lethal and nonlethal coagulopathy events. An ISTH DIC score of >=5 (the original
      ISTH criteria for overt DIC) was not associated with either early deaths or
      coagulopathy events. An ISTH DIC score threshold of 6, however, was significantly
      associated with early death (12% score >=6 vs. 0% score <6) and with both lethal
      and nonlethal coagulopathy events (35% score >=6 vs. 11% score <6). In pediatric
      APL patients, the presenting WBC is a marker for risk of early death. Although
      the ISTH score using a cutoff of >=6 showed improved correlation with adverse
      coagulation events during induction, the sensitivity was only 70.6% (95%
      confidence interval, 44.0%-89.7%) and the specificity was 64.5% (95% confidence
      interval, 51.3%-76.3%). Thus, there is a strong need to identify other biomarkers
      that can predict APL-associated coagulopathy.

PMID- 30095695
TI  - Population-based Cancer Registries are the Gold Standard to Cancer Incidence.

PMID- 30095697
TI  - Resilience Training for Work-Related Stress Among Health Care Workers: Results of
      a Randomized Clinical Trial Comparing In-Person and Smartphone-Delivered
      Interventions: Erratum.

PMID- 30095696
TI  - Pectoral Block Failure May Be Due to Incomplete Coverage of Anatomical Targets: A
      Dissection Study.
AB  - BACKGROUND AND OBJECTIVES: The popularization of ultrasound-guided nerve blocks
      in cosmetic and reconstructive breast surgery calls for better anatomical
      understanding of chest wall innervation. When inserting subpectoral implants,
      pain from pocket dissection, stretching of muscle, and release of costal
      attachments may be relieved by blocking the pectoral nerves in the interpectoral
      (IP) space.We describe the variable anatomy of the pectoral nerves in the IP
      space in order to define the area to be covered for sufficient blockade, based on
      cadaver dissections. METHODS: Twenty-six fresh cadavers were dissected
      bilaterally. The number, location, and course of the pectoral nerves were
      recorded. Distances to surface landmarks (sternum, clavicle, and costae) and
      ultrasound landmarks (thoracoacromial artery [TAA] and pectoralis minor muscle
      [Pm]) were recorded. RESULTS: The lateral pectoral nerve and the TAA entered
      together into the IP space 8.9 cm (range, 8.0-12.0 cm) lateral to the midsternal
      line. The medial pectoral nerve (MPN) had between 1 and 4 branches that pierced
      the Pm, and 69% had additional branches lateral to the Pm. The muscle-piercing
      MPN branches were located 3.8 cm (range, 0.4-8.1 cm) and the lateral MPN branches
      5.4 cm (range, 3.0-8.4 cm) from the lateral pectoral nerve. The IP course was 2.6
      cm (range, 0.7-6.5 cm). All specimens were asymmetrical in location or number of
      MPN branches. CONCLUSIONS: The MPN branches that innervate the lower part of the
      pectoralis major muscle are asymmetrical and variable in location and length; all
      located in a triangular area easily defined by sonographic landmarks, lateral to
      the TAA.

PMID- 30095698
TI  - Prevalence of Hearing Loss Among Noise-Exposed Workers Within the Health Care and
      Social Assistance Sector, 2003 to 2012: Erratum.

PMID- 30095701
TI  - The Influence of Chemotherapy-Induced Peripheral Neuropathy on Quality of Life of
      Gynecologic Cancer Survivors.
AB  - OBJECTIVE: The aim of this observational study was to investigate correlations
      between long-term chemotherapy-induced peripheral neurotoxicity (CIPN) and
      quality of life (physical well-being, social well-being, emotional well-being,
      and functional well-being [FWB]) among survivors of gynecologic cancer (GC).
      METHODS: We aimed to assess the correlation of quality of life and long-term CIPN
      with the temporal change in recurrence-free GC survival. Questionnaire responses
      and clinical data of 259 GC survivors were collected and assessed according to
      treatment received. The chi test was used to determine the significance of
      correlations. RESULTS: Of 165 evaluable patients treated by chemotherapy, 36
      patients (21.8%) developed CIPN of Common Toxicity Criteria for Adverse Events
      grade 1 or higher during the study. Chemotherapy-induced peripheral neurotoxicity
      had significantly improved over time in the domain of FWB at 61 months or more
      after the end of chemotherapy (posttreatment 4) among GC survivors (P = 0.003).
      Furthermore, CIPN treated by more than 6 courses of the paclitaxel and
      carboplatin regimen among GC survivors showed significant improvement over time
      in the emotional well-being domain at 25 to 60 months and 61 months or more after
      the end of chemotherapy (posttreatments 3 and 4) (P = 0.037 and P = 0.023) and in
      FWB at posttreatment 4 (P < 0.001). CONCLUSIONS: Emotional and functional domains
      of CIPN improved over time among GC survivors treated by more than 6 courses of
      the paclitaxel and carboplatin regimen. Based on these results, further research
      is required to identify additional preventative or curative approaches.

PMID- 30095703
TI  - Trends and Complications of Vulvar Reconstruction After Vulvectomy: A Study of a
      Nationwide Cohort.
AB  - OBJECTIVES: The objective of this study was to determine complications associated
      with primary closure compared with reconstruction after vulvar excision and
      predisposing factors to these complications. METHODS: Patients undergoing vulvar
      excision with or without reconstruction from 2011 to 2015 were abstracted from
      the National Surgical Quality Improvement Program database. Common Procedural
      Terminology codes were used to characterize surgical procedures as vulvar
      excision alone or vulvar excision with reconstruction. Patient characteristics
      and 30-day outcomes were used to compare the 2 procedures. Descriptive and
      univariate statistics were performed. Adjusted odds ratios and confidence
      intervals were calculated using a logistic regression model to control for
      potential confounders. Two-sided alpha with P < 0.05 was designated as
      significant. RESULTS: A total of 2698 patients were identified; 78 (2.9%)
      underwent reconstruction. There were no differences in age, race, body mass
      index, diabetes, hypertension, tobacco use, heart failure, renal failure, or
      functional status between the 2 groups. American Society of Anesthesiologists
      class 3 and 4 patients and those with disseminated cancer were more likely to
      undergo reconstruction (both P < 0.001). On univariate analysis, reconstruction
      was associated with increased risk of readmission, surgical site infection,
      pulmonary complications, urinary tract infection, transfusion, deep venous
      thrombosis, sepsis, septic shock, unplanned reoperation, longer hospital stay,
      need for skilled nursing or subacute rehab on discharge, and death within 30
      days. On logistic regression analysis, disseminated cancer, American Society of
      Anesthesiologists classes 3 and 4 and reconstruction remained significant risk
      factors for readmission and any postoperative complication. CONCLUSIONS: Patients
      undergoing vulvar excision with reconstruction are at increased risk for
      readmission and postoperative complications compared with those undergoing
      excision alone. Careful patient selection and efforts to optimize surgical
      readiness are needed to improve outcomes. Long-term data could help determine if
      these 30-day outcomes are a reliable measure of surgical quality in vulvar
      surgery.

PMID- 30095702
TI  - Propensity Score Analysis of Radical Hysterectomy Versus Definitive
      Chemoradiation for FIGO Stage IIB Cervical Cancer.
AB  - OBJECTIVE: The aim of this study was to compare the outcomes and toxicities of
      radical hysterectomy (RH) and definitive chemoradiation (CRT) for International
      Federation of Gynecology and Obstetrics (FIGO) stage IIB cervical cancer.
      MATERIALS AND METHODS: A retrospective analysis was performed on FIGO stage IIB
      patients who underwent RH with adjuvant radiotherapy (surgery group) or intended
      to receive CRT (CRT group). The distributions of disease-free survival (DFS) and
      overall survival (OS) were calculated using the Kaplan-Meier method. Propensity
      score matching (PSM) was performed for the 2 groups based on age, tumor diameter,
      histological type, and pelvic node metastasis in pretreatment imaging tests.
      RESULTS: Median follow-up times were 58 months in the surgery group (n = 75) and
      55 months in the CRT group (n = 65). Propensity score matching identified 37
      patients with similar characteristics from each group. Significant differences
      were observed in the ratio of the chemotherapy combination between the surgery
      and CRT groups before (47% vs 98%) and after PSM (51% vs 100%). Five-year DFS
      rates were slightly higher in the surgery group than in the CRT group before PSM
      (69% vs 58%, P = 0.30) but were similar after PSM (76% vs 82%, P = 0.36). Five
      year OS rates were similar between the surgery and CRT groups before (70% vs 75%,
      P = 0.59) and after PSM (78% vs 77%, P = 0.97). The results of multivariate
      analyses also showed that neither DFS nor OS was associated with the treatment
      modalities regardless of PSM. The incidence of late toxicities grade 2 or greater
      was similar between the surgery and CRT groups before (17% vs 23%, P = 0.31) and
      after PSM (19% vs 24%, P = 0.78). CONCLUSIONS: The results of this study suggest
      that RH with adjuvant radiotherapy and definitive CRT are equivalent treatment
      options for patients with FIGO stage IIB cancer. However, prospective larger
      studies are needed to confirm this.

PMID- 30095704
TI  - Diagnosis of Insufficiency Fracture After Radiotherapy in Patients With Cervical
      Cancer: Contribution of Technetium Tc 99m-Labeled Methylene Diphosphonate Single
      Photon Emission Computed Tomography/Computed Tomography.
AB  - : Insufficiency fractures (IFs) are a type of stress fracture caused by the
      effects of normal or physiological stresses on abnormally weakened bone.
      Frequently, these fractures are occult, and a portion of these fractures is
      misdiagnosed as bone metastases on a whole-body bone scan (WBS). The aim of this
      study was to evaluate a potential benefit of single-photon emission computed
      tomography/computed tomography (SPECT/CT) with metabolic and morphological
      imaging to diagnose IF in patients with cervical cancer after radiotherapy.
      METHODS: This article presents a retrospective review of 35 patients with
      cervical cancer after radiotherapy in patients (females; mean age, 55.94 +/- 8.75
      years; range, 36-73 years) who were referred to have WBS to determine whether
      there was any bone metastasis. The criterion standard was based on radiological
      investigations, clinical information, and follow-up at a minimum of 12 months.
      RESULTS: Insufficiency fractures were most frequently observed in the sacrum,
      accounting for 52.5% (21/40) of lesions. Fracture lines or sclerotic lines were
      noted in the IF lesion in 19 of 40 lesions on CT, and osteosclerosis was seen in
      31 of 40 lesions. On WBS analysis, the sensitivity for detected lesions was 87.5%
      (42/48) for WBS. Nineteen lesions were interpreted as benign, 6 lesions were
      malignant, and 21 (43.8%) lesions were equivocal. Based on the criterion
      standard, WBS had an accuracy of only 47.9% (23/48). On SPECT/CT analysis, all of
      the lesions were observed on SPECT/CT; only 3 (6.25%) of 48 lesions were
      equivocal, and the accuracy was 89.6% (43/48). CONCLUSIONS: Single-photon
      emission computed tomography/computed tomography should be included in the
      differential diagnoses when lesions show elevated technetium Tc 99m-labeled
      methylene diphosphonate uptake on WBS. Compared with a WBS alone, a more accurate
      diagnosis of IF can be obtained using SPECT/CT, which resulted not only in fewer
      equivocal lesions but also in a higher diagnostic accuracy.

PMID- 30095706
TI  - The LACC Trial: Has Minimally Invasive Surgery for Early-Stage Cervical Cancer
      Been Dealt a Knockout Punch?

PMID- 30095707
TI  - Endometrial Cancer Presentation and Outcomes Based on Mismatch Repair Protein
      Expression From a Population-Based Study.
AB  - OBJECTIVE: There is uncertainty about the prognostic significance of mismatch
      repair (MMR) deficiency in endometrial cancer. The objective was to evaluate
      clinical characteristics and outcomes of endometrial cancers based on MMR status
      within a population-based study. METHODS: This was a retrospective population
      based cohort study of all endometrial cancer cases from the Vancouver Coastal
      Health Authority region, evaluated for 4 MMR proteins using immunohistochemistry
      from 2012 to 2015. Patients were classified as MMR deficient (dMMR, any MMR
      protein absent) or MMR proficient (pMMR), Demographics, tumor characteristics,
      recurrences, and survival rates were compared according to MMR status. RESULTS:
      There were 892 patients, with 650 pMMR (72.5%) and 242 dMMR tumors. The dMMR
      group had more endometrioid tumors (87.6% vs 74.0%, P < 0.001), lymphovascular
      space invasion (43.8% vs 30.8%, P = 0.001), and dedifferentiation (5.9% vs 1.5%,
      P < 0.001), but fewer grade 1 tumors compared with the pMMR group (31.8% vs
      40.8%, P < 0.001). Median progression-free survival and overall survival have not
      been reached. After a median follow-up of 31 months (1-99 months), there was no
      difference in progression or recurrence rates between pMMR and dMMR tumors (19.5%
      vs 16.5%; P = 0.31). However, among those with nonendometrioid tumors, recurrence
      and mortality rates were significantly higher for pMMR than dMMR tumors (42.0% vs
      10.0%, P = 0.001, and 36.1% vs 13.1%, P = 0.01, respectively), despite similar
      stage and lymphovascular space invasion distributions. DISCUSSION: In this
      population-based study, there were no significant differences in recurrence or
      survival outcomes according to MMR status in endometrial cancer. However, among
      those with nonendometrioid tumors, there were lower recurrence and mortality
      rates associated with MMR-deficient compared with MMR-proficient tumors.

PMID- 30095705
TI  - Acute Myeloid Leukemia Following Gynecologic Cancer in the Era of Platinum-Based
      Chemotherapy.
AB  - OBJECTIVE: The aim of the present study was to estimate the risk of therapy
      related acute myeloid leukemia (t-AML) in patients with gynecologic malignancies
      receiving chemotherapy using a population-based database. METHODS: The National
      Cancer Institute's Surveillance, Epidemiology, and End Results database was
      accessed, and a cohort of women diagnosed with a primary ovarian, uterine, or
      cervical malignancy between January 1, 1992, and December 31, 2014, who received
      chemotherapy was selected. Those who subsequently developed AML were identified.
      Standardized incidence ratio (SIR) with 95% confidence intervals (CIs) and excess
      risk (ER) per 10,000 persons were calculated. Median overall survival of women
      with t-AML was calculated following generation of Kaplan-Meier curves. RESULTS:
      We identified 60,130 women who met the inclusion criteria; 56.4%, 19.4%, and
      24.2% were diagnosed with ovarian, cervical, and uterine cancer, respectively. A
      total of 79 patients (0.13%) developed t-AML. The calculated SIR was 4.41 (95%
      CI, 3.49-5.50). For women with ovarian, cervical, and uterine cancer, the SIRs
      were 4.25 (95% CI, 3.13-5.66), 5.33 (95% CI, 2.92-8.95), and 4.26, (95% CI, 2.52
      6.73), respectively. The highest risk was observed among women younger than 50
      years (SIR, 11.69; 95% CI, 7.56-17.25). Median interval between gynecologic
      cancer and t-AML diagnosis was 40 months (range, 3-218 months), whereas median OS
      following the diagnosis of t-AML was 4 months (95% CI, 1.52-6.48 months).
      CONCLUSIONS: Therapy-related AML following chemotherapy treatment for a
      gynecologic malignancy is a very rare late treatment-related event associated
      with a poor prognosis.

PMID- 30095708
TI  - Clinical Outcome After Completion Surgery in Patients With Ovarian Cancer: The
      Charite Experience.
AB  - OBJECTIVE: The aim of this study was to estimate surgical outcome and survival
      benefit after completion surgery. METHODS: We evaluated 164 patients with
      epithelial ovarian cancer who underwent incomplete primary cytoreductive surgery
      or rather received only staging procedures from January 2000 to December 2014 in
      outside institutions. Patient-related data were registered in prospective
      database of Tumor Bank Ovarian Cancer. The outcome analyses were performed for
      early and advanced stages of ovarian cancer separately. RESULTS: The majority of
      patients were at the time of completion surgery in advanced stages of disease.
      From overall 111 advanced epithelial ovarian cancer patients, 74 (66.6%) could be
      operated macroscopically tumor free, minimal residual disease 1 cm or less was
      achieved in 15.3% of the cases. Mean overall survival for patients without versus
      those with any tumor residual was 70 months (95% confidence interval, 61.3-81.5)
      versus 24.7 months (95% confidence interval, 7.1-42.4; P <= 0.0001). After
      applying completion surgery, 47 (28.6%) and 12 (6.7%) patients were upstaged in
      FIGO (International Federation of Gynecology and Obstetrics) IIIC and IV stages,
      respectively. Upstaging resulted in therapy changes in 10 patients (19%) with
      assumed FIGO IA stages. Major operative complications were registered in 28.8% of
      advanced cases, and 30-day mortality reached 1.8%. CONCLUSIONS: Recent research
      has shown that the most profound impact on survivorship occurs when women get
      proper care from surgeons trained in the latest techniques for treating ovarian
      cancer. Completion surgery maintained that even after initial incomplete
      cytoreduction outside of the high specialized units, after applying appropriate
      surgery techniques macroscopically, disease-free situation is achievable and
      outcomes are comparable with the results of primary debulking surgery.

PMID- 30095709
TI  - The Clinical Features of Recurrent Endometrial Cancer in Japan: Chemotherapy
      Instead of Radiotherapy as Postoperative Adjuvant Treatment.
AB  - OBJECTIVE: Chemotherapy is a standard adjuvant treatment after primary surgery
      for endometrial cancer in Japan. We aimed to characterize the clinical features
      of recurrent endometrial cancer (REC) patients in Japan. MATERIALS AND METHODS:
      We retrospectively reviewed the medical records of 112 REC patients who were
      primarily treated at 1 of 3 university hospitals in Japan from 2005 to 2012. We
      analyzed overall survival since the first recurrence (R-OS) in accordance with
      several factors. RESULTS: Median patient age was 64 years. The median follow-up
      period was 48 months. The distributions of cancer stage and histological subtype
      lacked distinctive features, and most patients had a high risk for recurrence at
      the time of the primary surgery. Although approximately 78% of patients received
      adjuvant chemotherapy, 85/112 patients (76%) experienced recurrence within 2
      years after the initial treatment ended. For patients receiving adjuvant
      chemotherapy, regional lymph node (LN) and distant-site recurrence were more
      frequent (>40%) than vaginal or intra-abdominal recurrence. Median survival and 5
      year R-OS were 27 months and 26.1%, respectively. The R-OS was significantly
      better for patients aged 65 years or older, those with negative peritoneal
      cytology at the time of primary surgery, those with recurrence within regional LN
      (eg, pelvic LN or para-aortic LN under the renal vein) and/or vagina, and those
      who underwent surgery and/or radiotherapy after recurrence. A multivariate
      analysis indicated that positive peritoneal cytology, a disease-free interval of
      less than 12 months, recurrent lesions in 2 or 3 areas, and treatment excluding
      surgery or radiotherapy were independent predictors of poor prognosis after
      recurrence. CONCLUSIONS: Adjuvant chemotherapy was insufficient to reduce the
      incidence of distant recurrence. The prognosis of patients recurred within
      regional LN and/or vagina was significantly better than that of patients with
      recurrence in other lesions because of treatment with surgery and/or
      radiotherapy. The disease-free interval was a significant prognostic factor for
      REC patients.

PMID- 30095710
TI  - Low-Risk Gestational Trophoblastic Neoplasia in Manitoba: Experience With
      Alternating Methotrexate and Dactinomycin.
AB  - OBJECTIVES: The aim of this study was to review the treatment and outcomes of low
      risk gestational trophoblastic neoplasia (GTN) in Manitoba over more than 3
      decades, with a focus on those treated with alternating methotrexate and
      dactinomycin, a protocol that has only rarely been described. MATERIALS AND
      METHODS: We retrospectively reviewed all patients with GTN referred to CancerCare
      Manitoba from January 1977 to December 2012. Cases were classified as low risk as
      per the modified WHO-FIGO prognostic scoring system (score, <=6). Demographic,
      treatment, and outcomes data were abstracted, and descriptive statistics and time
      to-event analysis were performed. The low-risk protocol used at CancerCare
      Manitoba consists of alternating single-agent use of methotrexate and
      dactinomycin, each for 5 days, on a 14-day cycle. RESULTS: Sixty-seven cases of
      GTN were identified, of which 52 were low risk. Thirty-nine patients were
      initiated on alternating methotrexate and dactinomycin. Thirty-four (87.2%)
      achieved primary cure on this regimen, with a median of 4.4 cycles administered
      (range, 2-7). Median time to response was 56 days. One patient achieved cure
      after receiving a repeat course of methotrexate as their final cycle. Second-line
      multiagent chemotherapy was required by 4 patients. Two patients experienced
      grade 3 toxicities, and none greater than grade 3. There were no recurrences.
      CONCLUSIONS: Alternating methotrexate and dactinomycin is an effective treatment
      protocol for low-risk GTN, with high rates of primary cure and acceptable
      toxicity.

PMID- 30095711
TI  - RETINAL-CHOROIDAL ANASTOMOSIS IN MACULAR TELANGIECTASIA TYPE 2.
AB  - PURPOSE: To investigate the deep retinal vascular changes potentially present in
      macular telangiectasis Type 2 (MacTel 2) with projection resolved optical
      coherence tomography angiography including volume rendering. METHODS:
      Retrospective consecutive evaluation of patients with MacTel 2 in a community
      based retinal referral practice with a comprehensive ophthalmologic examination
      to include optical coherence tomography and projection-resolved optical coherence
      tomography angiography with volume rendering. Main outcome measures were the
      characterization of vessel presence and anatomical arrangement in the outer
      retina. RESULTS: There were 26 eyes of 13 patients with a mean age of 64.9 (+/
      11.3) years, and 6 were men. The mean visual acuity was logMAR 0.4 (Snellen
      equivalent 20/50). No eye had signs of choroidal neovascularization or exudation.
      Focal hyperpigmentation was seen in 13 (50%) and right-angle veins in 17 (65%)
      eyes. Retinal-choroidal anastomoses were seen in 17 (65%) eyes. These anastomoses
      typically occurred in multiple clusters of small vessels. The presence of
      anastomoses was associated with pigment (P < 0.001), although the anastomoses did
      not necessarily colocalize with the pigment, and right-angle veins (P < 0.001),
      which were found in every eye with a retinal-choroidal anastomosis. CONCLUSION:
      Retinal-choroidal anastomoses were commonly observed in eyes with MacTel 2 using
      projection-resolved optical coherence tomography angiography. One animal model
      for MacTel 2 uses very low-density lipoprotein receptor mutant mice and shows
      multiple retinal-choroidal anastomoses in the disease pathogenesis as well. These
      findings suggest MacTel 2 is more than just a neurodegenerative disease with
      secondary vascular abnormalities, as the choroid may be involved in the disease
      process.

PMID- 30095712
TI  - The Therapeutic Index.

PMID- 30095713
TI  - Looking Under the Lamp Post, But You Dropped Your Keys Down the Street:
      Glucocorticoid Receptors in WBCs After Heart Surgery?

PMID- 30095714
TI  - Pediatric Critical Care Nursing Education and Certification Really Matters.

PMID- 30095715
TI  - Can We Replace Midazolam With Massage Therapy in the Pediatric Cardiac ICU?

PMID- 30095716
TI  - Settling the Score in Pulmonary Hypertension?

PMID- 30095717
TI  - Fat, Pharmacokinetics, and Fosphenytoin: Bigger Doses May Be Better.

PMID- 30095718
TI  - IV Lidocaine for Status Migraine: Making an "Off-Label" Treatment Decision.

PMID- 30095719
TI  - RBC Exposure in Pediatric Extracorporeal Membrane Oxygenation: Confusion Without
      Consensus.

PMID- 30095720
TI  - The Relevance of Parental Presence at the Bedside in Family-Partnered Care.

PMID- 30095721
TI  - Sick or Not SSIC? Time to Develop a Screening Tool for Early Identification of
      Sepsis in Children.

PMID- 30095722
TI  - IV Clonidine in the PICU: Time for Dexmedetomidine to Share the Limelight?

PMID- 30095723
TI  - Education of Healthcare Workers: Avoiding a Square Peg in a Round Hole.

PMID- 30095724
TI  - Dexmedetomidine During Noninvasive Ventilation: Some Practical Insights That
      Should Not Be Ignored.

PMID- 30095725
TI  - The authors reply.

PMID- 30095726
TI  - Asthma Severity Pathway in the PICU.

PMID- 30095727
TI  - The authors reply.

PMID- 30095728
TI  - Evaluation of the antihypertensive effect of nocturnal administration of
      acetylsalicylic acid: a cross-over randomized clinical trial.
AB  - OBJECTIVE: Several studies have shown that evening intake of aspirin has
      antihypertensive effect in healthy adults, which has not been proven in patients
      with cardiovascular disease, who mostly take aspirin in the morning. We have
      evaluated the antihypertensive effect of bedtime administration of aspirin in
      patients with cardiovascular disease already treated for hypertension. METHODS:
      This is a multicenter randomized triple-blind placebo-controlled crossover trial,
      with hypertensive patients treated with aspirin for secondary prevention. There
      was a baseline-randomized assignment to 2-month periods of bedtime aspirin (100
      mg) first and morning-time aspirin later, or inversely, both periods separated by
      an open label 2-4 weeks period of morning-time aspirin. At the start and end of
      each treatment period, a 24-h ambulatory blood pressure monitoring was performed.
      The main outcome measure was mean 24-h blood pressure. The analyses were
      performed according to the intention-to-treat principle. RESULTS: Overall, 225
      patients were randomized. No significant differences were observed in ambulatory
      blood pressure by time of intake of usual low doses of aspirin. The mean SBP/DBP
      was 123.2/69.9 (95% CI 121.58-124.9/68.86-76.86) with bedtime administration and
      122.4/68.8 (95% CI 120.76-124.01/67.85-69.83) with daytime administration (P =
      0.3 and P = 0.23 for SBP and DBP, respectively). CONCLUSION: Administering
      aspirin at bedtime rather than in the morning does not modify the 24-h ambulatory
      blood pressure in hypertensive patients in secondary cardiovascular
      prevention.The trial was registered with ClinicalTrials.gov (number NCT01741922).

PMID- 30095729
TI  - The State of the Science on Clinical Evaluation in Nursing Education.
AB  - AIM: The purpose was to synthesize the published evidence to present the state of
      the science in clinical evaluation research in nursing education. BACKGROUND:
      Clinical evaluation is key to ensuring nursing students' clinical competence,
      application of knowledge, and critical thinking, all of which are important to
      patient safety and quality nursing care. METHOD: Cooper's research synthesis
      method was used. RESULTS: A comprehensive literature search resulted in 250
      documents, of which 88 met study criteria. Topics were exhaustive but not
      mutually exclusive and included competence, instrumentation, congruence, teaching
      methods, objective structured clinical evaluation, faculty/preceptor issues with
      clinical evaluation, essential clinical behaviors, topic-based evaluation,
      decision-making about clinical grade, and clinical reasoning. CONCLUSION: Nursing
      education science is in its infancy in many areas. Two areas most in need of
      future research are the need to accurately define and efficiently measure
      competence in the clinical area and the need for reliable and valid
      instrumentation.

PMID- 30095730
TI  - An Integrative Review of Clinical Reasoning Teaching Strategies and Outcome
      Evaluation in Nursing Education.
AB  - BACKGROUND: This study explored teaching strategies used to promote clinical
      reasoning in nursing education and identify outcomes used to evaluate
      effectiveness. METHOD: The integrative review framework by Whittemore and Knafl
      (2005) was used in this study. RESULTS: Strategies included simulation (n = 10);
      active learning strategies such as case studies, reflection, journaling, and
      collaborative learning (n = 13); teaching strategies such as think aloud or case
      studies with simulation (n = 12); and experiential or clinical experiences (n =
      2). Although most studies used exams, worksheets (n = 19), or observations by
      clinical instructors (n = 2) to measure effectiveness, some studies (n = 8) also
      used surveys to measure student satisfaction, engagement, or perception; three
      studies measured the student's ability to use the instrument. CONCLUSION:
      Improving clinical thinking requires development of innovative, effective
      teaching strategies. Instruments that can accurately evaluate teaching and
      learning strategies are needed to advance this educational initiative and improve
      quality of care.

PMID- 30095731
TI  - Preparing the Nurse of the Future: Emergent Themes in Online RN-BSN Education.
AB  - AIM: Registered nurse to baccalaureate in nursing (RN-BSN) programs hold the
      second lowest average graduation rate of US nursing programs. Online education is
      often cited as a good fit for the working nurse for its convenience,
      accessibility, and flexibility. With a focus on supporting persistence in RN-BSN
      programs, this research sought to answer the question, What are the best
      practices for distance/online/hybrid RN to BSN program curriculum and
      instruction? BACKGROUND: Distance/online/hybrid approaches are a component of
      most RN-BSN programs and may hold promise for working nurses balancing multiple
      responsibilities while in school. METHOD: The Garrard Matrix Method was aligned
      with the work of Whittemore and Knafl to synthesize research that addressed the
      question. RESULTS: Four themes emerged through this synthesis. CONCLUSION: The
      findings serve as the beginning of a comprehensive guide on the subject.

PMID- 30095732
TI  - Integrating Social Media Into an Online Academic Program.
AB  - There is a noticeable gap in the literature regarding the programmatic
      integration of social media into health sciences education. Networked
      participatory scholarship theory supports the use of social media in higher
      education; associated benefits include promoting student engagement and real-time
      dissemination. This article describes the integration of social media use in a
      graduate online doctoral nursing program; specifically, blogging, microblogging,
      and ePortfolio integration are presented. The purpose is to improve students'
      utilization of social media as a professional tool.

PMID- 30095733
TI  - Evaluating the Effectiveness of ATI Nurse's TouchTM on BSN Student Soft Skills: A
      Descriptive Study.
AB  - Students in health care today are very different than those of past generations.
      Health care education requires both innovation and creativity to meet the
      changing needs of students. Soft skills such as leadership, communication,
      nursing informatics, technology, and professionalism can sometimes be lost in
      pursuit of scientific knowledge. The purpose of this descriptive pilot study was
      to evaluate the effectiveness of a product designed to assist in the development
      of soft skills in a bachelor of science in nursing curriculum. This research did
      not support the additive value of this particular product but recommended further
      research at other curricular levels.

PMID- 30095734
TI  - Barbell Hip-Thrust Exercise: Test-Retest Reliability and Correlation With
      Isokinetic Performance.
AB  - Dello Iacono, A, Padulo, J, Beslija, T, and Halperin, I. Barbell hip-thrust
      exercise: Test-retest reliability and correlation with isokinetic performance. J
      Strength Cond Res XX(X): 000-000, 2018-The barbell hip-thrust (BHT) exercise is
      growing in popularity as evident by the large increase in research outputs
      investigating its utility as a training intervention and a testing tool. The aim
      of this study was to examine the test-retest reliability of the BHT and its
      correlation with isokinetic performance. Test-retest reliability was established
      by correlating the peak force and power outcomes measured with the BHT force
      velocity profile test of 20 handball athletes on 2 separate days. The peak force
      and power measured with the BHT force-velocity profile test of 49 handball
      athletes were correlated with peak concentric force of the knee flexors and hip
      extensors measured with an isokinetic device at 2 different velocities (60-180
      degrees .s). The correlation between the isokinetic testing scores and the BHT
      force-velocity profile tests were moderate to large (Pearson r ranges: 0.45-0.86,
      all p values <0.001). Test-retest reliability of the BHT force-velocity profile
      was very high as shown with intraclass correlations of 0.94 and 0.99 for peak
      force and 0.97 and 0.99 for peak power measures. The BHT force-velocity profile
      can serve as a tentative substitute in cases that athletes do not have access to
      an isokinetic device, given the moderate to large correlations between them.
      Moreover, the BHT force-velocity profile was shown to be very reliable, thus
      providing coaches and scientists a range of day-to-day performance variability in
      this exercise.

PMID- 30095735
TI  - Validity and Reliability of Methods to Determine Barbell Displacement in Heavy
      Back Squats: Implications for Velocity-Based Training.
AB  - Appleby, BB, Banyard, H, Cormie, P, Cormack, SJ, and Newton, RU. Validity and
      reliability of methods to determine barbell displacement in heavy back squats:
      Implications for velocity-based training. J Strength Cond Res XX(X): 000-000,
      2018-The purpose of this study was to investigate the validity and reliability of
      methods for determining barbell displacement during heavy back squats. Twelve
      well-trained rugby union players (mean +/- SD 1 repetition maximum [1RM] 90
      degrees  squat = 196.3 +/- 29.2 kg) completed 2 sets of 2 repetitions at 70, 80,
      and 90% of 1RM squats. Barbell displacement was derived from 3 methods across 4
      load categories (120-129, 140-149, 160-169, and 180-189 kg) including: a (a)
      linear position transducer (LPT) attached 65 cm left of barbell center, (b) 3D
      motion analysis tracking of markers attached to either end of a barbell, and (c)
      cervical marker (C7) (criterion measurement). Validity was calculated using the
      typical error of the estimate as a coefficient of variation (CV%) +/-90%
      confidence interval (CI), mean bias as a percentage, and the Pearson product
      moment correlation (r). Intraday reliability was calculated using the intraclass
      correlation coefficient and the typical error expressed as a percentage of CV% +/
      90% (CI). Mean displacement for C7, LPT, and the barbell ends was 520, 529, and
      550-564 mm, respectively. Validity of the LPT compared with the criterion was
      acceptable (CV% = 2.1-3.0; bias = 0.9-1.5%; r = 0.96-0.98), whereas that of the
      barbell ends was less (CV% = 2.7-7.5; bias = 4.9-11.2%; r = 0.71-0.97). The CV%
      reliability of the C7 marker across the load categories was 6.6%, the LPT 6.6%,
      and the barbell ends between 5.9 and 7.2%. Despite reliable measures,
      overestimation of displacement occurs as the tracking location moves to the
      barbell ends in weighted back squats. The LPT demonstrated high validity to the
      criterion and high trial-to-trial reliability.

PMID- 30095736
TI  - Explosive Push-ups: From Popular Simple Exercises to Valid Tests for Upper-Body
      Power.
AB  - Zalleg, D, Ben Dhahbi, A, Dhahbi, W, Sellami, M, Padulo, J, Souaifi, M, Beslija,
      T, and Chamari, K. Explosive push-ups: From popular simple exercises to valid
      tests for upper-body power. J Strength Cond Res XX(X): 000-000, 2018-The purpose
      of this study was to assess the logical and ecological validity of 5 explosive
      push-up variations as a means of upper-body power assessment, using the factorial
      characterization of ground reaction force-based (GRF-based) parameter outputs.
      Thirty-seven highly active commando soldiers (age: 23.3 +/- 1.5 years; body mass:
      78.7 +/- 9.7 kg; body height: 179.7 +/- 4.3 cm) performed 3 trials of 5
      variations of the explosive push-up in a randomized-counterbalanced order: (a)
      standard countermovement push-up, (b) standard squat push-up, (c) kneeling
      countermovement push-up, (d) kneeling squat push-up, and (e) drop-fall push-up.
      Vertical GRF was measured during these exercises using a portable force plate.
      The initial force-supported, peak-GRF and rate of force development during
      takeoff, flight time, impact force, and rate of force development impact on
      landing were measured. A significant relationship between initial force-supported
      and peak-GRF takeoff was observed for the countermovement push-up (CMP) exercises
      (standard countermovement push-up, kneeling countermovement push-up, and drop
      fall push-up) and squat push-up (SP) exercises (standard squat push-up and
      kneeling squat push-up) (r = 0.58 and r = 0.80, respectively; p < 0.01).
      Furthermore, initial force supported was also negatively correlated to a
      significant degree with flight time for both CMP and SP (r = -0.74 and r = -0.80;
      p < 0.01, respectively). Principal component analysis (PCA) showed that the
      abovementioned 6 GRF-based variables resulted in the extraction of 3 significant
      components, which explained 88.9% of the total variance for CMP, and 2
      significant components, which explained 71.0% of the total variance for SP
      exercises. In summary, the PCA model demonstrated a great predictive power in
      accounting for GRF-based parameters of explosive push-up exercises, allowing for
      stronger logical and ecological validity as tests of upper-body power.
      Furthermore, it is possible to adjust the intensity level of the push-up exercise
      by altering the starting position (i.e., standard vs. kneeling).

PMID- 30095737
TI  - The Effect of Aspartate and Sodium Bicarbonate Supplementation on Muscle
      Contractile Properties Among Trained Men.
AB  - Farney, TM, MacLellan, MJ, Hearon, CM, Johannsen, NM, and Nelson, AG. The effect
      of aspartate and sodium bicarbonate supplementation on muscle contractile
      properties among trained men. J Strength Cond Res XX(X): 000-000, 2018-The focus
      of this investigation was to examine the effects of aspartate and NaHCO3
      supplementation on muscle contractile properties within trained men. Eleven men
      (21.9 +/- 1.5 years) ingested supplementation as 4 conditions all separated by 1
      week and included the following: placebo (PLA), L-aspartate (12.5 mg) (ASP),
      NaHCO3 (0.3 g.kg) (SBC), or combination of ASP and SBC (CBO). For each day of
      testing, participants performed 1 high-intensity exercise session along with a
      pre- and postexercise (pre- or postex) isometric mid thigh pull test to measure
      peak force (PF) production and rate of force development (RFD). Blood was
      collected for all testing sessions before and after the high-intensity exercise
      to determine ammonia accumulation (AMM). Exercise sessions consisted of 4
      exercises: barbell thrusters, squat jumps, lunge jumps, and forward jumps, with
      the total amount of work being equated for all 4 exercises across all 4 testing
      sessions. Participants performed the exercises in the aforementioned order, which
      was designated as 1 round. Each participant performed 3 rounds, with the work-to
      rest ratio being 20-second work, 30-second rest. A 1-minute rest was given
      between the rounds. There were no treatment effects (p > 0.05) for PF, RFD, or
      AMM. However, there was a significant main effect for supplement consumption for
      the total time of work with the ASP, SBC, and CBO treatments having a lower time
      to completion compared with the PLA treatment. Ammonia was significantly elevated
      postexercise (p = 0.004), whereas there were no differences from preexercise to
      postexercise for PF or RFD (p > 0.05). The only significant treatment * time
      interaction was for RFD (p = 0.03) with CBO increasing postexercise, with the
      other 3 treatments all decreasing postexercise. The combination of ASP and SBC
      together may have the potential to reduce fatigue by mitigating the effects of
      metabolic by-product accumulation.

PMID- 30095738
TI  - Oxygen Perfusion (Persufflation) of Human Pancreata Enhances Insulin Secretion
      and Attenuates Islet Proinflammatory Signaling.
AB  - BACKGROUND: All human islets used in research and for the clinical treatment of
      diabetes are subject to ischemic damage during pancreas procurement,
      preservation, and islet isolation. A major factor influencing islet function is
      exposure of pancreata to cold ischemia during unavoidable windows of preservation
      by static cold storage (SCS). Improved preservation methods may prevent this
      functional deterioration. In the present study, we investigated whether pancreas
      preservation by gaseous oxygen perfusion (persufflation) better preserved islet
      function versus SCS. METHODS: Human pancreata were preserved by SCS or by
      persufflation in combination with SCS. Islets were subsequently isolated, and
      preparations in each group matched for SCS or total preservation time were
      compared using dynamic glucose stimulated insulin secretion as a measure of beta
      cell function and RNA sequencing to elucidate transcriptomic changes. RESULTS:
      Persufflated pancreata had reduced SCS time, which resulted in islets with higher
      glucose stimulated insulin secretion compared to islets from SCS only pancreata.
      RNA sequencing of islets from persufflated pancreata identified reduced
      inflammatory and greater metabolic gene expression, consistent with expectations
      of reducing cold ischemic exposure. Portions of these transcriptional responses
      were not associated with time spent in SCS and were attributable to pancreatic
      reoxygenation. Furthermore, persufflation extended the total preservation time by
      50% without any detectable decline in islet function or viability. CONCLUSIONS:
      These data demonstrate that pancreas preservation by persufflation rather than
      SCS prior to islet isolation reduces inflammatory responses and promotes
      metabolic pathways in human islets, which results in improved beta cell function.

PMID- 30095739
TI  - CXCR4 Antagonist Reduced the Incidence of Acute Rejection and Controlled Cardiac
      Allograft Vasculopathy in a Swine Heart Transplant Model Receiving a
      Mycophenolate-based Immunosuppressive Regimen.
AB  - BACKGROUND: CXC motif chemokine receptor 4 (CXCR4) blockade is pursued as an
      alternative to mesenchymal stem cell treatment in transplantation based on our
      previous report that burixafor, through CXCR4 antagonism, mobilizes
      immunomodulatory mesenchymal stem cells. Here, we explored the efficacy of
      combining mycophenolate mofetil (MMF)-based immunosuppressants with repetitive
      burixafor administration. METHODS: Swine heterotopic cardiac allograft recipients
      received MMF and corticosteroids (control, n = 10) combined with burixafor as a 2
      dose (burixafor2D, n = 7) or 2-dose plus booster injections (burixafor2D + B, n =
      5) regimen. The efficacy endpoints were graft survival, freedom from first acute
      rejection, and the severity of intimal hyperplasia. Each specimen was sacrificed
      either at its first graft arrest or after 150 days. RESULTS: After 150 days, all
      specimens in the control group had died, but 28.5% of the burixafor2D group
      survived, and 60% of the burixafor2D + B group survived (P = 0.0088). Although
      the control group demonstrated acute rejection at a median of 33.5 days, the
      burixafor2D + B group survived without acute rejection for a median of 136 days
      (P = 0.0209). Burixafor administration significantly attenuated the incidence
      rate of acute rejection (P = 0.002) and the severity of intimal hyperplasia (P =
      0.0097) at end point relative to the controls. These findings were associated
      with reduced cell infiltrates in the allografts, and modulation of C-reactive
      protein profiles in the circulation. CONCLUSIONS: The augmentation of
      conventional MMF plus corticosteroids with a CXCR4 antagonist is potentially
      effective in improving outcomes after heart transplantation in minipigs. Future
      studies are warranted into optimizing the therapeutic regimens for humans.

PMID- 30095740
TI  - Peak Ventilation Reference Standards from Exercise Testing: From the FRIEND
      Registry.
AB  - PURPOSE: Cardiopulmonary exercise testing (CPX) provides valuable clinical
      information, including peak ventilation (VEpeak), which has been shown to have
      diagnostic and prognostic value in the assessment of patients with underlying
      pulmonary disease. This report provides reference standards for VEpeak derived
      from CPX on treadmills in apparently healthy individuals. METHODS: Nine
      laboratories in the United States experienced in CPX administration with
      established quality control procedures contributed to the Fitness Registry and
      the Importance of Exercise National Database from 2014 to 2017. Data from 5232
      maximal exercise tests from men and women without cardiovascular or pulmonary
      disease were used to create percentiles of VEpeak for both men and women by
      decade between 20 and 79 yr. Additionally, prediction equations were developed
      for VEpeak using descriptive information. RESULTS: VEpeak was found to be
      significantly different between men and women and across age groups (P < 0.05).
      The rate of decline in VEpeak was 8.0% per decade for both men and women. A
      stepwise regression model of 70% of the sample revealed that sex, age, and height
      were significant predictors of VEpeak. The equation was cross-validated with data
      from the remaining 30% of the sample with a final equation developed from the
      full sample (r = 0.73). Additionally, a linear regression model revealed forced
      expiratory volume in 1 s significantly predicted VEpeak (r = 0.73). CONCLUSIONS:
      Reference standards were developed for VEpeak for the United States population.
      Cardiopulmonary exercise testing laboratories will be able to provide
      interpretation of VEpeak from these age and sex-specific percentile reference
      values or alternatively can use these nonexercise prediction equations
      incorporating sex, age, and height or with a single predictor of forced
      expiratory volume in 1 s.

PMID- 30095741
TI  - Looking further when symptoms are disproportionate to physical findings.
AB  - A 36 year-old male presents with left ulnar-side wrist pain during an ice hockey
      game that prevented him from playing hockey or golf. There was no acute mechanism
      of injury. The usual clinical examination revealed only minimal tenderness and
      minimal pain with resisted wrist extension. Careful attention to precipitating
      factors led to testing resisted wrist extension with the forearm fully supinated,
      which reliably reproduced the intensity of the patient's symptoms, and a
      diagnosis of extensor carpi ulnaris tendinopathy. A literature review suggested
      three additional special tests (two were positive) and management. However, a
      standard of care has yet been established as neither the tests nor the management
      has been properly validated through research, thus leaving the management of this
      condition as an art.

PMID- 30095742
TI  - Normobaric Hypoxia Reduces VO2 at Different Intensities in Highly Trained
      Runners.
AB  - INTRODUCTION: We sought to determine the effect of low and moderate normobaric
      hypoxia on oxygen consumption and anaerobic contribution during interval running
      at different exercise intensities. METHODS: Eight runners (age: 25 +/- 7 years,
      VO2max: 72.1 +/- 5.6 ml.kg.min) completed three separate interval sessions at
      threshold (4 x 5 min, 2 min recovery), VO2max (8 x 90 s, 90 s recovery), and race
      pace (10 x 45 s, 1 min 45 s recovery) in each of; normoxia (elevation: 580 m,
      FiO2: 0.21), low (1400 m, 0.195) or moderate (2100 m, 0.18) normobaric hypoxia.
      The absolute running speed for each intensity was kept the same at each altitude
      to evaluate the effect of FiO2 on physiological responses. Expired gas was
      collected throughout each session, with total VO2 and accumulated oxygen deficit
      calculated. Data were compared using repeated measures ANOVA. RESULTS: There were
      significant differences between training sessions for peak and total VO2, and
      anaerobic contribution (p < 0.001, p = 0.01 respectively), with race pace
      sessions eliciting the lowest and highest responses respectively. Compared to 580
      m, total VO2 at 2100 m was significantly lower (p < 0.05), and anaerobic
      contribution significantly higher (p < 0.05) during both threshold and VO2max
      sessions. No significant differences were observed between altitudes for race
      pace sessions. CONCLUSION: To maintain oxygen flux, completing acute exercise at
      threshold and VO2max intensity at 1400 m simulated altitude appears more
      beneficial compared with 2100 m. However, remaining at moderate altitude is a
      suitable when increasing the anaerobic contribution to exercise is a targeted
      response to training.

PMID- 30095743
TI  - Demographic-specific Validity of the Cancer Prevention Study-3 Sedentary Time
      Survey.
AB  - PURPOSE: This study examined the one-year test-re-test reliability and criterion
      validity of sedentary time survey items in a subset of participants from a large,
      nationwide prospective cohort. METHODS: Participants included 423 women and 290
      men aged 31-72 years in the Cancer Prevention Study-3 (CPS-3). Reliability was
      assessed by computing Spearman correlation coefficients between responses from
      pre- and post-study surveys. Validity was assessed by comparing survey-estimated
      sedentary time with a latent variable representing true sedentary time estimated
      from the seven-day diaries, accelerometry, and surveys through the method of
      triads. Sensitivity analyses were restricted to 566 participants with an average
      of 14+ hours of diary and accelerometer data per day for seven days per quarter.
      RESULTS: Reliability estimates for total sitting time were moderate or strong
      across all demographic strata (Spearman rho>=0.6), with significant differences
      by race (p=0.01). Reliability estimates were strongest for the TV-related
      sedentary time item (Spearman rho=0.74, 95% CI: 0.70, 0.77). The overall validity
      coefficient (VC) for survey-assessed total sedentary time was 0.62 (95% CI: 0.55,
      0.69), although VCs varied by age group and activity level (p<0.05). However, VCs
      were similar across groups (p<0.05) when restricting to highly compliant
      participants in a sensitivity analysis.CONCLUSIONThe CPS-3 sedentary behavior
      questionnaire has acceptable reliability and validity for ranking or categorizing
      participants according to sedentary time. Acceptable reliability and validity
      estimates persist across various demographic sub-groups.

PMID- 30095744
TI  - Supraspinal Fatigue and Neural-evoked Responses in Lowlanders and Sherpa at 5050
      m.
AB  - PURPOSE: At high-altitude, Lowlanders exhibit exacerbated fatigue and impaired
      performance. Conversely, Sherpa (native Highlanders) are known for their
      outstanding performance at altitude. Presently, there are no reports comparing
      neuromuscular fatigue and its etiology between Lowlanders and native Sherpa at
      altitude. METHODS: At 5050 m, nine age-matched Lowlanders and Sherpa (31+/-10 vs.
      30+/-12 years, respectively) completed a 4-minute sustained isometric elbow
      flexion at 25% maximal voluntary (MVC) torque. Mid-minute, stimuli were applied
      to the motor cortex and brachial plexus to elicit a motor evoked potential (MEP)
      and maximal compound muscle action potential (Mmax), respectively. Supraspinal
      fatigue was assessed as the reduction in cortical voluntary activation (cVA) from
      pre- to post-fatigue. Cerebral haemoglobin concentrations and tissue oxygenation
      index (TOI) were measured over the prefrontal cortex by near-infrared
      spectroscopy. RESULTS: Pre-fatigue, MVC torque and cVA were significantly greater
      for Lowlanders than Sherpa (79.5+/-3.6 vs. 50.1+/-11.3N.m, and 95.4+/-2.7 vs.
      88.2+/-6.6%, respectively). With fatigue, MVC torque and cVA declined similarly
      for both groups (~24-26% and ~5-7%, respectively). During the task, MEP area
      increased more and sooner for Lowlanders (1.5min) than Sherpa (3.5min). Mmax area
      was lower than baseline throughout fatigue for Lowlanders but unchanged for
      Sherpa. TOI increased earlier for Lowlanders (2min) than Sherpa (4min). Total
      haemoglobin increased only for Lowlanders (2min). Mmax was lower while TOI and
      total haemoglobin were higher for Lowlanders than Sherpa during the second half
      of the protocol. CONCLUSION: Although neither MVC torque loss nor development of
      supraspinal fatigue was different between groups, neural evoked responses and
      cerebral oxygenation indices were less perturbed in Sherpa. This represents an
      advantage for maintenance of homeostasis, presumably due to bequeathed genotype
      and long-term altitude adaptations.

PMID- 30095745
TI  - Fat-free Mass Characteristics of Muscular Physique Athletes.
AB  - PURPOSE: Simple body composition models, such as two-compartment models, employ
      assumptions which may be violated in specific athletic populations (e.g. the
      constancy of fat-free mass density [DFFM] and hydration [TBW:FFM]). The present
      analysis examined FFM characteristics of muscular physique athletes. METHODS:
      Twenty-six athletes (16 M: 94.5+/-9.9 kg, 12.2+/-4.2 %fat; 10 F: 63.8+/-5.7 kg,
      19.7+/-4.9 %fat) completed duplicate assessments of dual-energy x-ray
      absorptiometry (DXA), bioimpedance spectroscopy (BIS), and single- and multi
      frequency bioelectrical impedance analysis (SFBIA; MFBIA). FFM was calculated via
      5-compartment (5C) model, and FFM characteristics (i.e. DFFM, TBW: FFM, FFM
      mineral, FFM protein) were compared between sexes and between the sample and
      reference values (RV) from cadaver analysis. TBWBIS: FFM5C was designated as the
      reference TBW:FFM model, and alternate models were produced using BIS, MFBIA,
      SFBIA, impedance-based equations, and DXA output. RESULTS: Males had lower
      TBW:FFM and FFM mineral, but higher FFM protein than females (p<0.05). DFFM was
      significantly lower than RV in males (1.096+/-0.006 g/cm, RV: 1.103+/-0.013 g/cm;
      p<0.001) and appeared higher in females (1.093+/-0.012 g/cm, RV: 1.087+/-0.021
      g/cm; p=0.17). TBW:FFM did not differ from RV in females (75.3+/-4.0%, RV: 75.7+/
      4.4%; p=0.74) or males (72.7+/-1.9%, RV: 72.7+/-3.1%; p=0.97). FFM mineral was
      lower than RV in males (5.5+/-0.4%, RV: 6.8+/-0.8%; p<0.001) and higher in
      females (6.5+/-0.5%, RV: 6.1+/-0.8%; p=0.04). FFM protein was significantly
      greater than RV in males (21.9+/-1.8%, RV: 20.6+/-2.6%; p=0.014), but the
      difference from RV in females was not statistically significant (18.3+/-4.1%, RV:
      17.1+/-4.5%; p=0.39). Alternate TBW:FFM models varied substantially in their
      agreement with RV. CONCLUSIONS: FFM characteristics were shown to differ between
      male and female physique athletes. These results may have implications for
      optimal body composition assessment methods when atypical physique
      characteristics are present.

PMID- 30095746
TI  - Randomized Study of Early Continuous Positive Airways Pressure in Acute
      Respiratory Failure in Children With Impaired Immunity (SCARF) ISRCTN82853500.
AB  - OBJECTIVES: Previous trials in adults with impaired immunity and respiratory
      failure suggest that early noninvasive ventilation avoids endotracheal intubation
      and improves survival. No randomized clinical trials have addressed this question
      in children. DESIGN: We undertook an open, parallel-group randomized trial in
      three pediatric hospitals. SUBJECTS: Children with impaired immunity and acute
      respiratory failure defined as tachypnoea (> 90th centile); a new requirement for
      supplemental oxygen; and new chest radiograph infiltrates. INTERVENTIONS:
      Children were randomly assigned to early PICU admission for continuous positive
      airways pressure (early continuous positive airways pressure) or to standard
      care. The primary outcome was endotracheal intubation by 30 days. MEASUREMENTS
      AND MAIN RESULTS: One-hundred fourteen children met inclusion criteria of whom 42
      were randomized between January 2013 and January 2016. There was no significant
      difference in endotracheal intubation by 30 days with early continuous positive
      airways pressure (10/21; 48%) compared with standard care (5/21; 24%), odds ratio
      2.9 (0.8-10.9), p value equals to 0.11. However, 30-day mortality was
      significantly higher with early continuous positive airways pressure (7/21; 33%)
      compared with standard care (1/21; 5%), odds ratio 10.0 (1.1-90.6), p value
      equals to 0.041. Mortality at 90 days was early continuous positive airways
      pressure (11/21; 52%) versus standard care (4/21; 19%), odds ratio 4.7 (1.2
      18.6), p value equals to 0.029, whereas mortality at 1 year was similar early
      continuous positive airways pressure (13/21; 61.9%) versus standard care (9/21;
      42.7%), odds ratio 2.2 (0.6-7.4), p value equals to 0.22. There were two serious
      adverse events: early continuous positive airways pressure (pneumothorax) and
      standard care (hemothorax). CONCLUSIONS: This study provided no evidence to
      support early PICU admission for continuous positive airways pressure in children
      with acute respiratory failure and impaired immunity. There was a trend toward
      increased endotracheal intubation and a higher early mortality in the early
      continuous positive airways pressure group.

PMID- 30095748
TI  - Multicenter Validation of the Vasoactive-Ventilation-Renal Score as a Predictor
      of Prolonged Mechanical Ventilation After Neonatal Cardiac Surgery.
AB  - OBJECTIVES: We sought to validate the Vasoactive-Ventilation-Renal score, a novel
      disease severity index, as a predictor of outcome in a multicenter cohort of
      neonates who underwent cardiac surgery. DESIGN: Retrospective chart review.
      SETTING: Seven tertiary-care referral centers. PATIENTS: Neonates defined as age
      less than or equal to 30 days at the time of cardiac surgery. INTERVENTIONS:
      Ventilation index, Vasoactive-Inotrope Score, serum lactate, and Vasoactive
      Ventilation-Renal score were recorded for three postoperative time points: ICU
      admission, 6 hours, and 12 hours. Peak values, defined as the highest of the
      three measurements, were also noted. Vasoactive-Ventilation-Renal was calculated
      as follows: ventilation index + Vasoactive-Inotrope Score + Delta creatinine
      (change in creatinine from baseline * 10). Primary outcome was prolonged duration
      of mechanical ventilation, defined as greater than 96 hours. Receiver operative
      characteristic curves were generated, and abilities of variables to correctly
      classify prolonged duration of mechanical ventilation were compared using area
      under the curve values. Multivariable logistic regression modeling was also
      performed. MEASUREMENTS AND MAIN RESULTS: We reviewed 275 neonates. Median age at
      surgery was 7 days (25th-75th percentile, 5-12 d), 86 (31%) had single ventricle
      anatomy, and 183 (67%) were classified as Society of Thoracic Surgeons-European
      Association for Cardio-Thoracic Surgery Congenital Heart Surgery Mortality
      Category 4 or 5. Prolonged duration of mechanical ventilation occurred in 89
      patients (32%). At each postoperative time point, the area under the curve for
      prolonged duration of mechanical ventilation was significantly greater for the
      Vasoactive-Ventilation-Renal score as compared to the ventilation index,
      Vasoactive-Inotrope Score, and serum lactate, with an area under the curve for
      peak Vasoactive-Ventilation-Renal score of 0.82 (95% CI, 0.77-0.88). On
      multivariable analysis, peak Vasoactive-Ventilation-Renal score was independently
      associated with prolonged duration of mechanical ventilation, odds ratio (per 1
      unit increase): 1.08 (95% CI, 1.04-1.12). CONCLUSIONS: In this multicenter cohort
      of neonates who underwent cardiac surgery, the Vasoactive-Ventilation-Renal score
      was a reliable predictor of postoperative outcome and outperformed more
      traditional measures of disease complexity and severity.

PMID- 30095749
TI  - Energy Intake and Expenditure in Children With Heart Failure.
AB  - OBJECTIVES: Up to one third of children with heart failure exhibit growth
      failure. Limited data exists reporting energy requirements in this population. A
      study was designed to characterize the energy intake and total daily energy
      expenditure of children with heart failure using the doubly labeled water method.
      DESIGN: Prospective study using doubly labeled water to measure total daily
      energy expenditure in children with heart failure. Doubly labeled water was
      administered orally and daily urine samples collected for 10 days. Total daily
      energy expenditure was compared with historic data from age- and gender-matched
      healthy population. Anthropometrics and 3-day calorie count were also done.
      SETTING: The Cardiovascular Intensive Care Unit and Cardiology ward at Texas
      Children's Hospital. PATIENTS: Children with new presentation of heart failure as
      defined by an ejection fraction less than 35% and requiring inotrope(s) at the
      time of enrollment. MEASUREMENTS AND MAIN RESULTS: A total of five children with
      heart failure were enrolled from 2015 to 2016. All children showed weight-for
      length less than mean-for-age. All had depressed myocardial function at
      enrollment, and all but one demonstrated improvement in ejection fraction at
      follow-up. Three had energy intake that met or surpassed their total daily energy
      expenditure, with total daily energy expenditure that measured below historic
      controls. One infant, despite supplementation, had an energy intake substantially
      below that of measured total daily energy expenditure and required cardiac
      transplantation. CONCLUSIONS: Growth failure in heart failure is likely
      multifactorial and may be related to suboptimal energy intake secondary to
      exercise intolerance, malabsorption, and/or end-organ dysfunction due to impaired
      cardiac output. Doubly labeled water is a feasible method to assess total daily
      energy expenditure in children with heart failure.

PMID- 30095750
TI  - Thermal Behavior Differs between Males and Females during Exercise and Recovery.
AB  - INTRODUCTION: This study tested the hypothesis that females rely on thermal
      behavior to a greater extent during and following exercise, relative to males.
      METHODS: In a 24+/-1 degrees C; (45+/-10% RH) environment, 10 males (M) and 10
      females (F) (22+/-2 y) cycled for 60 min (metabolic heat production-M: 117+/-18;
      F: 129+/-21 W.m), followed by 60 min recovery. Mean skin and core temperatures,
      skin blood flow and local sweat rates were measured continually. Subjects
      controlled the temperature of their dorsal neck to perceived thermal comfort
      using a custom-made device. Neck device temperature provided an index of thermal
      behavior and mean body temperature provided an index of the stimulus for thermal
      behavior. Data were analyzed for total area under the curve (AUC) for exercise
      and recovery time points. To further isolate the effect of exercise on thermal
      behavior during recovery, data were also analyzed the minute mean body
      temperature returned to pre-exercise levels within a subject. RESULTS: There were
      no sex differences in metabolic heat production (P=0.71) or body temperatures
      (P>=0.10) during exercise. AUC for neck device temperature during exercise was
      greater for F (-98.4+/-33.6 vs. -64.5+/-47.8 degrees C.min, P=0.04), but did not
      differ during recovery (F: 86.8+/-37.8; M: 65.6+/-35.9 degrees C.min, P=0.11). In
      M, mean skin (P=0.90), core (P=0.70) and neck device (P=0.99) temperatures had
      recovered by the time that mean body temperature had returned to pre-exercise
      levels. However, in F, neck device temperature (P=0.04) was reduced while core
      temperature remained elevated (P<0.01). CONCLUSIONS: F utilize thermal behavior
      during exercise to a greater extent than M. During recovery, thermal behavior may
      compensate for elevated core temperatures in F despite mean body temperatures
      returning to pre-exercise levels.

PMID- 30095747
TI  - Interleukin-1 Receptor Antagonist Is Associated With Pediatric Acute Respiratory
      Distress Syndrome and Worse Outcomes in Children With Acute Respiratory Failure.
AB  - OBJECTIVES: To test whether plasma interleukin-1 receptor antagonist or variants
      within the gene encoding for interleukin-1ra (IL1RN), or proteins involved in
      regulating interleukin-1beta levels or interleukin-1beta response, are associated
      with pediatric acute respiratory distress syndrome or outcomes in mechanically
      ventilated children with parenchymal lung disease. DESIGN: Prospective cohort
      study. SETTING: Twenty-two PICUs participating in the multisite clinical trial,
      Randomized Evaluation of Sedation Titration for Respiratory Failure (U01
      HL086622). SUBJECTS: Children 2 weeks to 17 years old treated with invasive
      mechanical ventilation for acute airways and/or parenchymal lung disease.
      MEASUREMENTS AND MAIN RESULTS: Three-hundred seventy-eight of 549 patients had
      pediatric acute respiratory distress syndrome; DNA and plasma were obtained from
      523 of 549 and 480 of 549 patients, respectively. Plasma interleukin-1ra was
      highest on the day of intubation (day 0) and decreased over the subsequent 3 days
      (p < 0.0001). Interleukin-1ra level was higher in patients with pediatric acute
      respiratory distress syndrome than those without pediatric acute respiratory
      distress syndrome (p < 0.0001). Multivariable regression analysis of data across
      all days demonstrated a significant association of interleukin-1ra (odds ratio,
      1.30; 95% CI, 1.10-1.52; p = 0.002) and day (p < 0.05) with pediatric acute
      respiratory distress syndrome, independent of age and Pediatric Risk of Mortality
      III score. Analysis on individual days indicated that plasma interleukin-1ra
      levels were associated with pediatric acute respiratory distress syndrome on days
      0 and 2, independent of age and Pediatric Risk of Mortality-III score (p = 0.04
      and 0.003, respectively), however did not quite reach significance on days 1 and
      3 (p = 0.06 and 0.07, respectively). Interleukin-1ra was independently associated
      with mortality on day 1 (p = 0.02). Interleukin-1ra also correlated with length
      of mechanical ventilation, measures of oxygenation, and PICU length of stay. No
      genetic variants were associated with pediatric acute respiratory distress
      syndrome. CONCLUSIONS: Plasma interleukin-1ra is associated with pediatric acute
      respiratory distress syndrome, PICU length of stay, length of mechanical
      ventilation, and mortality in children with acute respiratory failure requiring
      mechanical ventilation.

PMID- 30095751
TI  - How Sickle Cell Disease Impairs Skeletal Muscle Function: Implications in Daily
      Life.
AB  - Sickle cell disease (SCD) is the most frequent life-threatening genetic
      hemoglobinopathy in the world and occurs due to the synthesis of abnormal
      hemoglobin S (HbS). HbS-containing red blood cells (RBCs) are fragile, leading to
      hemolysis and anemia, and adhere to the endothelium, leading to hemorheological
      and hemodynamical disturbances. In its deoxygenated form, HbS may polymerize,
      leading to sickling of RBCs and potentially to vaso-occlusive crises. Recent
      findings observed that sickle cell disease patients demonstrate significant
      skeletal muscle remodeling and display reduced muscle functional capacities,
      contributing to exercise intolerance and poor quality of life. While acute high
      intensity exercise is not recommended for sickle cell disease patients as it may
      increase the risk of sickling, regular moderate-intensity physical activity could
      have beneficial effects on skeletal muscle and more generally on the well-being
      of sickle cell disease patients. This paper reviews the literature regarding the
      impact of the disease on muscular tissue characteristics and function, as well as
      the corresponding implications for SCD patients' quality of life.

PMID- 30095752
TI  - PCNA News.

PMID- 30095754
TI  - Do Depressed Elderly Heart Failure Patients Benefit From Yoga? A Future Direction
      for Research.

PMID- 30095753
TI  - Self-care: An Update on the State of the Science One Decade Later.

PMID- 30095755
TI  - Contraception for Women With Intellectual and Developmental Disabilities:
      Reproductive Justice.

PMID- 30095756
TI  - What Is New in Opioids?: Best Articles From the Past Year.
AB  - This month we focus on current research in opioids. Dr. Schorge discusses five
      recent publications, which are concluded with a "bottom-line" that is the take
      home message. A complete reference for each can be found on on this page along
      with direct links to abstracts.

PMID- 30095757
TI  - Connect the Dots-September 2018.

PMID- 30095758
TI  - The Unyielding Fight Against the Premature Death of Patients With Advanced-Stage
      Ovarian Cancer.

PMID- 30095759
TI  - Rattlesnake Envenomation in the Third Trimester of Pregnancy.
AB  - BACKGROUND: Snakebites in pregnancy can be life-threatening to both the mother
      and fetus as a result of inflammatory and toxic properties of the venom. Prompt
      medical treatment is critical to prevent adverse consequences. CASE: A 26-year
      old woman at 37 6/7 weeks of gestation was bitten by a rattlesnake on the right
      middle finger, resulting in severe pain radiating up to the upper arm and
      swelling involving the entire hand. A total of 18 vials of crotalidae polyvalent
      immune fab was administered over 11 hours. Three days after the incident, the
      patient delivered a healthy neonate vaginally and without complications. Both
      mother and newborn were well at 1-month follow-up. CONCLUSION: Our case supports
      managing snakebites in pregnancy similar to managing cases in nonpregnant
      individuals, including using crotalidae polyvalent immune fab antivenom.

PMID- 30095760
TI  - Maternal and Fetal Risk Associated With Assisted Reproductive Technology.
AB  - Infertility is a disease that affects up to 15.5% of reproductive-aged couples.
      Until the birth of the first neonate born from in vitro fertilization (IVF) in
      1978, many infertile couples did not have an opportunity to conceive a biological
      child. Over the past 40 years, access to and effectiveness of IVF have increased;
      currently 1.7% of births in the United States result from IVF. As with any
      medical intervention, potential risk exists. In the case of IVF, both maternal
      risks (ovarian stimulation, oocyte retrieval, and subsequent pregnancy) and fetal
      risks that vary based on maternal age and fetal number must be considered.
      Importantly, risk quantification varies by comparison group, which is typically
      either spontaneous conception in a fertile couple or assisted non-IVF conception
      in an infertile couple. It must also be considered compared with the alternative
      of not undergoing IVF, which may mean not having a biological child. Although
      increased compared with spontaneous conception, absolute maternal-fetal-assisted
      reproductive technology risks are low and can be minimized by optimizing ovarian
      stimulation and transferring a single embryo. In this article, we aim to
      summarize maternal and fetal risk associated with use of assisted reproductive
      technology. The review focuses on ovarian stimulation and procedural risks as
      well as adverse perinatal outcomes among resultant singleton and twin pregnancies
      in young women and women of advanced maternal age.

PMID- 30095761
TI  - Evaluating Adherence to Guideline-Based Quality Indicators for Postpartum
      Hemorrhage Care in the Netherlands Using Video Analysis.
AB  - OBJECTIVE: To assess adherence to the national postpartum hemorrhage guideline
      and Managing Obstetric Emergencies and Trauma course instructions and its
      determinants in the Netherlands. METHODS: A prospective observational multicenter
      study in 16 Dutch hospitals analyzing data from medical records of 398 women at
      high risk for postpartum hemorrhage, of which 293 were supplemented with data
      from prospective video recordings. Adherence to guideline-based quality
      indicators for prevention, management, and organization of postpartum hemorrhage
      care was measured. Indicators for prevention and management of postpartum
      hemorrhage were categorized according to the amount of blood loss (less than 500,
      greater than 500, greater than 1,000, and greater than 2,000 mL). RESULTS:
      Overall, a lack of adherence was observed, particularly for the actions to be
      undertaken with blood loss greater than 1,000 mL (69 patients). Actions were not
      or only taken in a later stage when the blood loss had already increased to
      greater than 2,000 mL (21 patients). In almost 41% (n=119/293) of the deliveries,
      no active management was performed, and in almost 80% (n=89/112), vital signs
      were not monitored (blood loss greater than 500 mL) or monitored too late with
      respect to blood loss. The video recordings showed that in general the actual
      care given was considerably underreported in medical records. Postpartum
      hemorrhage care in the hospitals was well organized. Fifteen hospitals had a
      local postpartum hemorrhage protocol, and in 12 hospitals, team trainings were
      organized. Regarding the determinants, high-risk patient identification and type
      of hospital (university vs nonuniversity hospital) were mostly associated with
      better adherence. CONCLUSION: This study showed low adherence to the guideline
      based quality indicators, indicating a problem with Dutch quality care. The
      unique video observations provided additional, valuable information at which
      level improvement can be made. A tailor-made implementation strategy to improve
      quality of postpartum hemorrhage care has been developed. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT00928863.

PMID- 30095762
TI  - Prophylactic Pregabalin to Decrease Pain During Medication Abortion: A Randomized
      Controlled Trial.
AB  - OBJECTIVE: To evaluate whether prophylactic pregabalin reduces pain experienced
      with medication abortion. METHODS: We conducted a randomized, double-blind,
      placebo-controlled trial of women initiating medication abortion with
      mifepristone and buccal misoprostol up to 70 days of gestation. Participants were
      randomized to 300 mg oral pregabalin or a placebo immediately before misoprostol.
      The primary outcome was maximum pain on an 11-point numerical rating scale,
      reported using real-time electronic surveys over 72 hours. Secondary outcomes
      included pain at each time point, ibuprofen and narcotic use, side effects, and
      satisfaction. We estimated that 110 women would be required to have 80% power to
      detect a difference in pain of 1.3 points. RESULTS: Between June 2015 and October
      2016, 241 women were screened and 110 were randomized (56 pregabalin, 54
      placebo). Three were lost to follow-up. The primary outcome of mean maximum pain
      in the pregabalin group was 5.0+/-2.6 vs 5.5+/-2.2 in the placebo group (P=.32).
      Excluding medication taken before the study capsule, ibuprofen was used by 64%
      (35/55) of the pregabalin group vs 87% (45/52) placebo (P<.01). Narcotics were
      used by 29% (16/55) of the pregabalin group vs 50% (26/52) placebo (P<.03). More
      dizziness (P<.001), sleepiness (P<.04), and blurred vision (P<.05) occurred in
      the pregabalin group. Satisfaction scores for the analgesic regimen were higher
      in the pregabalin group (very satisfied: 47% vs 22%; P=.006). CONCLUSION:
      Compared with placebo, 300 mg pregabalin coadministered with misoprostol during
      medication abortion did not significantly decrease maximum pain scores. Women who
      received pregabalin were less likely to require any ibuprofen or narcotic and
      were more likely to report higher satisfaction with analgesia, despite an
      increase in dizziness, sleepiness, and blurred vision. CLINICAL TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02782169.

PMID- 30095763
TI  - Sexual Orientation and Exposure to Violence Among U.S. Patients Undergoing
      Abortion.
AB  - OBJECTIVE: To assess the characteristics of patients undergoing abortion in the
      United States according to sexual orientation and exposure to sexual and physical
      violence. METHODS: Data for this observational study come from the Guttmacher
      Institute's 2014 Abortion Patient Survey, which obtained information from 8,380
      individuals obtaining abortions at nonhospital facilities in the United States;
      7,656 of those (91%) provided information on sexual orientation identity. We used
      simple logistic regression to assess differences between heterosexuals and three
      sexual minority groups-bisexual, lesbian, and something else-according to
      demographic characteristics and exposure to sexual and physical violence.
      Multivariate logistic regression was used to assess associations between sexual
      orientation and exposure to violence. RESULTS: Among patients undergoing abortion
      in 2014, 4.1% identified as bisexual (n=316), 1.1% as something else (n=81), and
      0.4% as lesbian (n=28); 94.4% identified as heterosexual (n=7,231). Similar
      proportions of lesbian and heterosexual respondents reported a prior birth (53.6%
      and 58.2%, P=.62), whereas respondents who identified as something else were more
      likely to report having had a prior abortion (58.0% vs 43.9%, P=.01). Exposure to
      sexual violence was substantially and significantly higher among all three sexual
      minority groups compared with heterosexuals, and lesbian and bisexual respondents
      were also more likely than their heterosexual peers to report exposure to
      physical violence by the man involved in the pregnancy (33.3% and 8.7% vs 3.6%,
      P<.001). CONCLUSION: No patient should be presumed to be heterosexual.
      Understanding the disproportionate role of sexual violence in unintended
      pregnancies among sexual minorities may aid in the design of interventions and
      clinical guidelines that address the needs of sexual minority patients.

PMID- 30095764
TI  - Role of Preexposure Prophylaxis in the Reproductive Health of Women at Risk for
      Human Immunodeficiency Virus Infection.
AB  - Women in the United States and especially women of color continue to acquire
      human immunodeficiency virus (HIV) infection. During reproductive health visits,
      health care providers are ideally positioned to assess HIV risk and offer HIV
      prevention strategies, including preexposure prophylaxis (also known as "PrEP"),
      a once-daily fixed-dose combination of emtricitabine with tenofovir disoproxil
      fumarate approved by the U.S. Food and Drug Administration for use to prevent HIV
      acquisition in persons at risk. Family planning, pregnancy, and postpartum visits
      provide an opportunity to ask sensitive questions about sexual and reproductive
      health and to help women navigate preference-sensitive decisions, including an
      individualized plan for HIV prevention. Exposure to a fixed-dose combination of
      emtricitabine with tenofovir disoproxil fumarate during pregnancy and
      breastfeeding appears to be safe with respect to maternal and infant outcomes.
      This article reviews the critical issues, challenges, and opportunities when
      implementing preexposure prophylaxis for women at risk for HIV who are seeking
      family planning services or pregnancy or postpartum care.

PMID- 30095765
TI  - Implementation of a Quality Improvement Initiative to Decrease Opioid Prescribing
      After Cesarean Delivery.
AB  - OBJECTIVE: To assess whether a multiphase, departmental quality improvement
      effort decreases opioid prescribing and increases multimodal analgesic use after
      cesarean delivery. METHODS: This is a prospective quality improvement study. In
      phase 1 of the protocol, discharge providers implemented counseling regarding
      expectations for pain, typical need for opioids, and importance of multimodal
      nonopioid analgesic use and used shared decision-making to determine the number
      of opioids prescribed. Patients could select up to a maximum of 30 tablets of 5
      mg oxycodone (or equivalent opioid), lower than the previous routine discharge
      prescription of 40 opioid tablets. The primary outcome was the mean (SD) number
      of opioid tablets prescribed on discharge with secondary outcomes including
      opioid refill rate within 30 days of discharge and rates of nonopioid analgesic
      prescriptions on discharge. In phase 2, using these results, we adjusted the
      protocol's maximum opioid prescription to 25 opioid tablets, but no other aspects
      of the protocol were changed. All data were analyzed with t test and chi
      analyses. RESULTS: Data from 624 women who underwent cesarean deliveries were
      analyzed. Opioids, most commonly oxycodone, were prescribed after 95% of all
      cesarean deliveries. The mean (SD) number of opioid tablets prescribed decreased
      from 33.2 (9.3) to 26.5 (6.7; P<.01) with the implementation of phase 1 having no
      effect on the opioid refill rate, 8.9% vs 8.1% (P=.79). These results allowed
      adjustment of the maximum recommended prescription to 25 opioid tablets,
      introducing phase 2 of the study, during which the mean (SD) number of opioid
      tablets prescribed further decreased from 24.9 (7.5) to 21.5 (6.3; P<.01) with no
      effect on the opioid refill rate, 6.3% vs 5.1% (P=.72). Overall, this represents
      a 35% decrease in opioid prescribing (P<.01). Rates of ibuprofen prescribing were
      98% or higher throughout the study, but rates of acetaminophen prescribing
      increased from 32.6% before phase 1 to 92.0% after phase 2 (P<.001). CONCLUSION:
      Implementation of a multiphase quality improvement protocol to decrease opioid
      prescribing, combined with iterative review of discharge data, resulted in a
      significant decrease in the number of opioid tablets prescribed after cesarean
      delivery.

PMID- 30095766
TI  - Adjuvant Use of Rifampin for Refractory Intrahepatic Cholestasis of Pregnancy.
AB  - BACKGROUND: Intrahepatic cholestasis of pregnancy is an incompletely understood
      disease that poses significant fetal risks, including stillbirth. Treatment of
      intrahepatic cholestasis of pregnancy is aimed at relieving maternal symptoms and
      improving fetal outcomes. CASE: A 21-year-old gravid woman, 3 para 0111,
      presented at 27 2/7 weeks of gestation with severe intrahepatic cholestasis of
      pregnancy. Her clinical course was refractory to first-line therapy with
      ursodiol, and she was started on rifampin with rapid improvement of symptoms and
      transaminitis. Despite maternal improvement, she was delivered at 31 weeks of
      gestation for persistent nonreassuring fetal status. CONCLUSION: Rifampin may be
      an effective adjunctive therapy for intrahepatic cholestasis of pregnancy
      refractory to ursodiol alone. Additional research is needed to assess short-term
      and long-term maternal and newborn outcomes, because fetal deterioration still
      occurred in spite of maternal improvement.

PMID- 30095767
TI  - Repeat Screening for Syphilis in the Third Trimester of Pregnancy: A Cost
      Effectiveness Analysis.
AB  - OBJECTIVE: To estimate the cost-effectiveness of screening all women during the
      first and third trimesters compared with screening just once during pregnancy.
      METHODS: We used a theoretical cohort of 3.9 million women in the United States
      to model syphilis screening approaches in pregnancy, particularly comparing one
      time screening with repeat third-trimester screening. Outcomes of syphilis
      infection included in the model were congenital syphilis, intrauterine fetal
      demise, neonatal death, and total quality-adjusted life-years (QALYs).
      Probabilities, utilities, and costs were obtained from the literature, and a cost
      effectiveness threshold was set at $100,000 per QALY. A societal perspective was
      assumed. RESULTS: Our model demonstrated that repeat screening in the third
      trimester for syphilis in pregnancy will result in fewer maternal and neonatal
      adverse outcomes and higher QALYs when compared with screening once in the first
      trimester. Specifically, we demonstrated that repeat screening results in 41
      fewer neonates with evidence of congenital syphilis, 73 fewer cases of
      intrauterine fetal demise, 27 fewer neonatal and infant deaths, in addition to a
      cost savings of $52 million and 4,000 additional QALYs. CONCLUSION: Using our
      baseline assumptions, our data support that in pregnancy, repeat screening for
      syphilis is superior to single screening during the first trimester and is both
      cost-effective and results in improvement in maternal and neonatal outcomes. When
      screening policies are being created for pregnant women, the cost-effectiveness
      of repeat screening for syphilis should be considered.

PMID- 30095768
TI  - Disparities in Human Papillomavirus Vaccine Completion Rates Among Females in an
      Integrated Health Care System.
AB  - OBJECTIVE: To estimate the rate of human papillomavirus (HPV) vaccine completion
      by race and ethnicity. METHODS: In this retrospective cohort study, we analyzed
      females aged 11-26 years who initiated HPV vaccination from 2008 through 2012 in
      a community-based health care system in California. Vaccine completion was
      defined as having received at least three injections. Demographic data including
      age, race, ethnicity, and language preferences were obtained. Among Hispanic
      patients, acculturation was categorized as low or high using written and spoken
      Spanish vs English language as a proxy. Age groups were defined as younger
      adolescents (11-14 years), teens (15-17 years), and young adults (18-26 years).
      Bivariate analyses using chi tests and age-adjusted logistic regression were
      performed. RESULTS: Among 102,052 females who initiated HPV vaccination, a total
      of 41,847 (41%) completed the series. Younger adolescents had the highest
      completion rates (43.4%, P<.001) vs teens and young adults (37.4% and 38.0%,
      respectively). By race and ethnicity, Asian patients had the highest completion
      rates (49.5%, 95% CI 48.8-50.2), and the lowest rates were seen among black and
      Hispanic patients (28.7% [95% CI 27.8-29.6] and 38.9% [95% CI 38.3-39.5],
      respectively). Among Hispanic patients, the adjusted odds for vaccine completion
      was 1.2-fold higher for the low acculturated vs the highly acculturated group
      (adjusted odds ratio 1.23 [95% CI 1.16-1.31]). CONCLUSION: More than half of the
      females who initiated HPV vaccination did not complete the series, and black and
      Hispanic patients were least likely to have completed the series. Among Hispanic
      patients, the highest acculturated group had the lowest completion rate. These
      disparities emphasize the need for cancer prevention across all racial and ethnic
      groups.

PMID- 30095769
TI  - Cervical Pessary After Arrested Preterm Labor: A Randomized Controlled Trial.
AB  - OBJECTIVE: To assess the effectiveness of cervical pessary in reducing the rate
      of preterm birth in women at high risk for preterm birth who did not deliver
      after an episode of threatened preterm labor. METHODS: In a multicenter open
      label randomized controlled trial, a cervical pessary was compared with no
      intervention (control group) (one-to-one ratio). Women between 24 and 34 weeks of
      gestation at high risk for preterm birth based on a short cervical length (less
      than 15 mm) or an intermediate cervical length (between 15 and 30 mm) with a
      positive fetal fibronectin test who did not deliver after an episode of
      threatened preterm labor were eligible. The primary outcome was birth before 37
      weeks of gestation. Secondary outcomes were a composite adverse neonatal outcome,
      preterm birth before 34 and 32 weeks of gestation, and side effects. A total
      sample size of 200 women carrying singletons was planned so as to have adequate
      statistical power to detect a reduction in the rate of preterm birth from 40% to
      20%. Women with twin gestations were also enrolled but were considered only in
      secondary analyses. After a planned interim analysis, the trial was stopped for
      futility. RESULTS: From November 2013 through September 2016, 130 women with a
      singleton pregnancy (65 pessary, 65 no treatment) were recruited. The groups had
      comparable baseline characteristics. In the cervical pessary group, 31 (48%)
      women delivered before 37 weeks of gestation compared with 25 (39%) in the no
      treatment group (relative risk 1.2, 95% CI 0.83-1.8). Nine (15%) children in the
      cervical pessary group had the composite adverse perinatal outcome compared with
      eight (13%) in the control group (relative risk 1.2, 95% CI 0.49-2.9).
      CONCLUSION: In women at high risk for preterm birth who did not deliver after an
      episode of threatened preterm labor, treatment with a cervical pessary is not
      effective. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register, NTR4210.

PMID- 30095770
TI  - The Rise and Fall of Mesh in Pelvic Surgery and the Shortcomings of Medical
      Device Regulation.
AB  - Two U.S. Food and Drug Administration public health warnings regarding the use of
      mesh in stress incontinence and prolapse repairs have had far-reaching clinical
      and legal consequences. In this commentary, we explore the drastically distinct
      results from these mesh-based procedures, which revealed systemic flaws with the
      medical device approval process across specialties and affected thousands of
      patients.

PMID- 30095771
TI  - Provision of Moderately and Highly Effective Reversible Contraception to Insured
      Women With Intellectual and Developmental Disabilities.
AB  - OBJECTIVE: To estimate provision of moderately and highly effective reversible
      contraceptives to women with intellectual and developmental disabilities.
      METHODS: We used data from the Massachusetts All-Payer Claims Database to
      identify women aged 15-44 years with and without intellectual and developmental
      disabilities who were continuously enrolled in a private commercial insurance
      plan, Medicaid, or Medicare in 2012. We calculated the percentage of women aged
      15-44 years who were not medically or surgically sterile and were provided 1)
      highly effective, long-acting reversible contraception (LARC, the intrauterine
      device or subdermal implant); or 2) prescriptions for moderately effective
      methods (pill, patch, ring, shot, or diaphragm). Logistic regression models
      estimated the odds of LARC and moderately effective method provision by
      disability status, adjusted for age, income, and Medicaid receipt. RESULTS: Among
      915,561 women who were not medically or surgically sterile, 13,059 women (1.4%)
      had at least one intellectual and developmental disability. Women with
      intellectual and developmental disabilities were less likely to be provided LARC
      (2.1% vs 4.2%, P<.001, adjusted odds ratio [OR] 0.43, 95% CI 0.38-0.48, P<.001)
      and moderately effective methods (21.1% vs 29.9%, P<.001, adjusted OR 0.68, 95%
      CI 0.65-0.71, P<.001) than women without intellectual and developmental
      disabilities. The one exception was the progestin shot, which was provided more
      often to women with intellectual and developmental disabilities than women
      without these disabilities (14.7% vs 4.3%, P<.001). Among a subset of women who
      only received moderately effective methods or LARC (n=310,344), women with
      intellectual and developmental disability had lower odds of receiving LARC than
      moderately effective methods (adjusted OR 0.59, 95% CI 0.52-0.67). CONCLUSION:
      The study findings raise concerns that the provision of LARC and moderately
      effective methods differs based on the presence of intellectual and developmental
      disabilities. Greater understanding is needed regarding factors that underlie
      lower provision of LARC in comparison with moderately effective methods,
      especially the progestin shot, among women with intellectual and developmental
      disabilities.

PMID- 30095772
TI  - Association of a Health Care Provider Review Meeting With Cesarean Delivery
      Rates: A Quality Improvement Program.
AB  - OBJECTIVE: To examine the association of a quality improvement effort that was
      mediated through weekly review of all criteria for cesarean delivery on cesarean
      delivery prevalence and indications. METHODS: We conducted a retrospective cohort
      study using a natural experiment model that compared two timeframes, from 2009 to
      2013, at a single institution. We introduced a weekly retrospective review
      conference to discuss all cesarean deliveries in 2010 that continued over time.
      The conferences were attended by obstetric care providers, anesthesiology, and
      labor and delivery nurses. Date of delivery was dichotomized by those delivering
      before July 1, 2010, and those delivering after. We included women with term
      singleton vertex gestations in our study population and then examined the rates
      of cesarean delivery by date of delivery. We then examined indications for the
      cesarean deliveries during the study period based on surgeon documentation. chi
      tests were used for statistical comparisons and a P value of <.05 was used to
      indicate statistical significance. RESULTS: There were 5,541 term singleton
      cephalic births during the study period. The rate of cesarean delivery declined
      significantly after our intervention in all women (22.2% vs 27.4%, P<.001) and
      nulliparous women (23.3% vs 30.9%, P<.001). The adjusted odds ratio of cesarean
      delivery in all women as related to time cohort is 0.68 (95% CI 0.58-0.79) and
      0.56 (95% CI 0.44-0.70) in nulliparous women. We examined indications for the
      1,315 cesarean deliveries during the study period by date of delivery. The
      indications of active-phase arrest, second-stage arrest, failed induction, repeat
      cesarean delivery, and maternal request decreased significantly between delivery
      cohorts in all women (P<.001) and in nulliparous women specifically (P<.001).
      Between delivery cohorts, we found that the prevalence of labored indications for
      cesarean delivery decreased more than nonlabored indications. CONCLUSION:
      Implementation of a weekly review conference was associated with a reduction in
      both overall cesarean delivery prevalence and labored indications at our
      institution.

PMID- 30095773
TI  - Individualized Compared With Standard Postdischarge Oxycodone Prescribing After
      Cesarean Birth: A Randomized Controlled Trial.
AB  - OBJECTIVE: To evaluate whether individualized postdischarge oxycodone prescribing
      guided by inpatient opioid use reduces the number of unused opioid tablets after
      cesarean birth. METHODS: We conducted a randomized, controlled trial of women
      aged 18 years or older undergoing cesarean birth. Participants were randomized at
      discharge in a 1:1 ratio to a standard (30 tablets of 5 mg oxycodone) or an
      individualized oxycodone prescription (predicted based on each patient's
      inpatient opioid use). All women were contacted starting 14 days after cesarean
      birth to assess number of oxycodone tablets used and adequacy of pain control.
      The Tennessee Controlled Substance Monitoring Database was accessed to confirm
      dispensed opioids. The primary outcome was number of unused oxycodone tablets
      prescribed for pain control after cesarean birth. A total sample size of 160
      women was necessary to detect a 30% difference in leftover tablets between groups
      with 80% power and alpha of 0.05. RESULTS: Between June 14, 2017, and August 26,
      2017, we screened 323 women and randomized 172. Baseline characteristics and
      inpatient opioid use were similar between groups. Women in the individualized
      group were prescribed fewer tablets (14 [interquartile range 12-16] vs 30
      [interquartile range 30-30], P<.001) and had 50% fewer unused tablets than women
      in the standard group (5 [interquartile range 1-8] vs 10 [interquartile range 0
      22], P<.001). Overall, 13% (23/172) used no opioids after discharge and 26%
      (44/172) used all prescribed opioids. There were no differences between the
      standard and individualized groups in the proportion of women who used no opioids
      or all opioids and no difference in the proportion of dispensed opioids used (60%
      [interquartile range 23-100] vs 61% [29-89], P=.93). Women in the individualized
      group used only half the number of prescribed opioids as women in the standard
      group (8 [interquartile range 4-14] vs 15 [interquartile range 6-30], P<.001).
      Patient-reported pain outcomes did not differ significantly by group. CONCLUSION:
      Individualized opioid prescribing based on inpatient use reduces the number of
      unused oxycodone tablets compared with standard prescribing. CLINICAL TRIALS
      REGISTRATION: ClinicalTrials.gov, NCT03168425.

PMID- 30095774
TI  - Female Sterilization and Cognitive Disability in the United States, 2011-2015.
AB  - OBJECTIVE: To compare female sterilization among three mutually exclusive groups
      of females: 1) those without any self-reported disability, 2) those with
      noncognitive disabilities (sensory or physical disabilities), and 3) those with
      cognitive disabilities. METHODS: We conducted a secondary analysis of nationally
      representative data from the National Survey of Family Growth 2011-2015, which
      surveyed individuals aged 15-44 years in the U.S. civilian population. Disability
      status (self-reported) was ascertained using a standard set of questions about
      hearing, vision, cognitive, ambulatory, self-care, and independent living
      difficulties. Regression models were used to calculate odds of female
      sterilization, hysterectomies, and age of sterilization while accounting for
      sociodemographic differences. RESULTS: Female sterilization rates were higher
      among females with cognitive (22.1% [n=272]) and noncognitive disabilities (24.7%
      [n=150]) than among those without disabilities (14.8% [n=1,132]). After adjusting
      for sociodemographic covariates, females with cognitive disabilities had
      significantly higher odds of female sterilization (adjusted odds ratio [OR] 1.54,
      95% CI 1.19-1.98, P<.01) and hysterectomy (adjusted OR 2.64, 95% CI 1.53-4.56,
      P<.001) than those without cognitive disabilities. Females with cognitive
      disabilities also underwent sterilization at significantly younger ages (27.3
      years, 95% CI 27.0-27.6) than those with noncognitive disabilities (28.3 years,
      95% CI 27.9-28.8) and those without any disability (29.8 years, 95% CI 29.5
      30.0). CONCLUSION: U.S. females with cognitive disabilities were more likely to
      have undergone female sterilizations and hysterectomies and at younger ages than
      those with other disabilities or without disabilities. Drivers of these
      disability-related differences in female sterilization patterns must be explored.

PMID- 30095775
TI  - Risk of Severe Acute Maternal Morbidity According to Planned Mode of Delivery in
      Twin Pregnancies.
AB  - OBJECTIVE: To evaluate the association between the planned mode of delivery and
      severe acute maternal morbidity in women with twin pregnancies. METHODS: In this
      planned secondary analysis of the JUmeaux MODe d'Accouchement cohort, a national
      prospective population-based study of twin deliveries conducted from February
      2014 to March 2015 in 176 hospitals performing more than 1,500 annual deliveries
      in France, we included women with twin pregnancies at 24 weeks of gestation or
      greater with two live fetuses. Women delivering before 24 weeks of gestation,
      those with recognized indications for cesarean delivery, and those with severe
      acute maternal morbidity symptomatic before labor were excluded to limit
      confounding by indication. The primary outcome was a composite measure of intra-
      or postpartum severe acute maternal morbidity. Multivariate Poisson regression
      models and propensity score matching were used to control for potential
      confounding by indication. Analyses were conducted for the overall study cohort
      as well as stratified by maternal age in years (younger than 30, 30-34, 35 years
      or older). No adjustments were made for multiple comparisons. RESULTS: Among the
      8,124 women included in this analysis, 3,062 (37.7%) had planned cesarean
      deliveries and 5,062 (62.3%) had planned vaginal deliveries, of whom 4,015
      (79.3%) delivered both twins vaginally. No significant overall association was
      found between the planned mode of delivery and severe acute maternal morbidity
      (6.1% in the planned cesarean delivery group and 5.4% in the planned vaginal
      group; adjusted relative risk 1.00, 95% CI 0.81-1.24). In women 35 years or
      older, the risk of severe acute maternal morbidity was significantly higher for
      those with planned cesarean delivery than planned vaginal delivery (7.8% vs 4.6%,
      adjusted relative risk 1.44, 95% CI 1.02-2.06). Propensity score and secondary
      analyses yielded similar results. CONCLUSION: In twin pregnancies, there is no
      overall association between planned mode of delivery and severe acute maternal
      morbidity. Women older than 35 years may be at higher risk of severe acute
      maternal morbidity after planned cesarean delivery.

PMID- 30095776
TI  - Paracervical Block for Intrauterine Device Placement Among Nulliparous Women: A
      Randomized Controlled Trial.
AB  - OBJECTIVE: To investigate whether a 20-mL buffered 1% lidocaine paracervical
      block decreases pain during intrauterine device (IUD) placement. METHODS: In a
      randomized, single-blind, placebo-controlled trial, women were assigned to
      receive either a 20-mL buffered 1% lidocaine paracervical block or no block
      before IUD placement. The primary outcome was pain with IUD placement measured on
      a 100-mm visual analog scale. Our sample size had 80% power (alpha=0.05) to
      detect a 20-mm difference in visual analog scale scores with a SD of 28 mm.
      Secondary outcomes included pain with speculum placement, paracervical block
      administration, tenaculum placement, 5 minutes postprocedure, and overall pain
      perception. RESULTS: From October 7, 2014, through October 26, 2017, 64 women
      were enrolled and analyzed (33 in the paracervical block arm, 31 in the no-block
      arm). There were no differences in baseline demographics between the groups.
      Women who received the paracervical block reported less pain with IUD placement
      compared with women who received no block (median visual analog scale score of 33
      mm vs 54 mm, P=.002). Pain was significantly less in the intervention group for
      uterine sounding (30 mm vs 47 mm, P=.005), 5 minutes after placement (12 mm vs 27
      mm, P=.005), and overall pain perception (30 mm vs 51 mm, P=.015). Participants
      who received the paracervical block experienced more pain with block
      administration compared with placebo (30 mm vs 8 mm, P=.003). There was no
      perceived pain difference for speculum insertion (10 mm vs 6 mm, P=.447) or
      tenaculum placement (15 mm vs 10 mm, P=.268). CONCLUSION: A 20-mL buffered 1%
      lidocaine paracervical block decreases pain with IUD placement (primary outcome),
      uterine sounding (secondary outcome), and 5 minutes after placement (secondary
      outcome). Although paracervical block administration can be painful, perception
      of pain for overall IUD placement procedure is lower compared with no block.
      CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02219308.

PMID- 30095777
TI  - Effectiveness of Fertility Awareness-Based Methods for Pregnancy Prevention: A
      Systematic Review.
AB  - OBJECTIVE: To summarize best available prospective data on typical and perfect
      use effectiveness of fertility awareness-based methods for avoiding pregnancy.
      DATA SOURCES: We conducted a systematic review of studies published in English,
      Spanish, French, or German by June 2017 in MEDLINE, EMBASE, CINAHL, Web of
      Science, and ClinicalTrials.gov. METHODS OF STUDY SELECTION: We reviewed 8,755
      unique citations and included 53 studies that contained 50 or greater women using
      a specific fertility awareness-based method to avoid pregnancy, calculated life
      table pregnancy probabilities or Pearl rates, and prospectively measured
      pregnancy intentions and outcomes. We systematically evaluated study quality.
      TABULATION, INTEGRATION, AND RESULTS: Of 53 included studies, we ranked 0 high
      quality, 21 moderate quality, and 32 low quality for our question of interest.
      Among moderate-quality studies, first-year typical use pregnancy rates or
      probabilities per 100 woman-years varied widely: 11.2-14.1 for the Standard Days
      Method, 13.7 for the TwoDay Method, 10.5-33.6 for the Billings Ovulation Method,
      4-18.5 for the Marquette Mucus-only Method, 9.0-9.8 for basal body temperature
      methods, 13.2 for single-check symptothermal methods, 11.2-33.0 for Thyma double
      check symptothermal methods, 1.8 for Sensiplan, 25.6 for Persona, 2-6.8 for the
      Marquette Monitor-only Method, and 6-7 for the Marquette Monitor and Mucus
      Method. First-year perfect use pregnancy rates or probabilities among moderate
      quality studies were 4.8 for the Standard Days Method, 3.5 for the TwoDay Method,
      1.1-3.4 for the Billings Ovulation Method, 2.7 for the Marquette Mucus Method,
      0.4 for Sensiplan, 12.1 for Persona, and 0 for the Marquette Monitor. CONCLUSION:
      Studies on the effectiveness of each fertility awareness-based method are few and
      of low to moderate quality. Pregnancy rates or probabilities varied widely across
      different fertility awareness-based methods (and in some cases, within method
      types), even after excluding low-quality studies. Variability across populations
      studied precludes comparisons across methods.

PMID- 30095778
TI  - Balloon Uterine Tamponade Device After Peripartum Hysterectomy for Morbidly
      Adherent Placenta.
AB  - BACKGROUND: Perioperative hemorrhage is a common complication of peripartum
      hysterectomy for morbidly adherent placenta. We present an application of a
      balloon uterine tamponade device in the setting of a cesarean delivery and
      subsequent supracervical hysterectomy for abnormal placentation. CASE: A 33-year
      old gravid woman, 6 para 3022, at 33 2/7 weeks of gestation was admitted in
      preterm labor, with placenta previa and suspected morbidly adherent placenta, for
      a planned cesarean delivery and hysterectomy. After supracervical hysterectomy,
      colloid resuscitation and packing failed to provide hemostasis. A transcervical
      balloon uterine tamponade device subsequently was placed intraperitoneally and
      left on tension owing to the need for further tamponade. CONCLUSION: Use of a
      balloon uterine tamponade device intraperitoneally posthysterectomy was
      associated with hemorrhage control. This application may facilitate timely
      management and streamlining of obstetric resources for postpartum hemorrhage.

PMID- 30095779
TI  - The Adverse Outcome Index: Putting Quality Into an Outcome Measure.
AB  - The Adverse Outcome Index, originally designed to provide an objective inventory
      of adverse outcomes, is often promoted as a tool for assessing the quality of
      inpatient obstetric care. Although the Adverse Outcome Index is well described,
      and its outcomes are easy to collect, it has notable drawbacks such as
      "paradoxical measures" (eg, blood transfusions are counted as adverse measures
      even when they are used appropriately) and the dominance of certain measures
      within the Adverse Outcome Index that can drive scores (eg, neonatal intensive
      care unit admissions). In this article, we argue that in addition to the
      limitations noted, the Adverse Outcome Index, although providing a reasonable
      measure of inpatient obstetric acuity, fails to be a reliable measure of quality.
      This is particularly important because many organizations are seeking quality
      measures and the Adverse Outcome Index may become a candidate tool. We believe
      that introducing an adjudication process to the Adverse Outcome Index would
      greatly enhance its role as a quality indicator. Until newly proposed quality
      measures are perfected and adopted, a quality-adjusted Adverse Outcome Index will
      allow this widely used measure to provide a more reliable determination of those
      adverse events potentially amenable to performance improvement.

PMID- 30095781
TI  - The First National Summit on Women's Health: The Future of Obstetrics and
      Gynecology Training.
AB  - OBJECTIVE: To identify the current challenges in obstetrics and gynecology
      residency education and propose solutions to overcome these obstacles. METHODS:
      The American College of Obstetricians and Gynecologists (ACOG) hosted the first
      National Summit on Women's Health on May 31 and June 1, 2017, with a follow-up
      meeting December 20-21, 2017, at ACOG headquarters in Washington, DC. Invitees
      from 20 related societies briefly presented their organizations' perspectives and
      discussed focused questions about specific challenges, proposed solutions, and
      anticipated obstacles. Finally, participants summarized their top two
      recommendations to improve current residency training. RESULTS: Summit
      participants identified four primary areas of focus: 1) align curriculum with
      relevant topics to practice, 2) ensure faculty have the necessary resources and
      time to teach effectively, 3) consider using the final months of medical school
      to get a jump start on residency fund of knowledge and skills, and 4) use better
      assessments during the course of residency. CONCLUSION: Representatives of the
      Council on Resident Education in Obstetrics and Gynecology, the American Board of
      Obstetrics and Gynecology, and the Accreditation Council for Graduate Medical
      Education must work together to address these priorities and reach consensus on
      the curricular content of core training in obstetrics and gynecology.

PMID- 30095780
TI  - Risk of Cervical Intraepithelial Neoplasia 2 or Worse by Cytology, Human
      Papillomavirus 16/18, and Colposcopy Impression: A Systematic Review and Meta
      analysis.
AB  - OBJECTIVE: To calculate pooled risk estimates for combinations of cytology
      result, human papillomavirus (HPV) 16/18 genotype and colposcopy impression to
      provide a basis for risk-stratified colposcopy and biopsy practice. DATA SOURCE:
      A PubMed search was conducted on June 1, 2016, and a ClinicalTrials.gov search
      was conducted on June 9, 2018, using key words such as "uterine cervical
      neoplasms," "cervical cancer," "mass screening," "early detection of cancer," and
      "colposcopy." METHODS OF STUDY SELECTION: Eligible studies must have included
      colposcopic impression and either cytology results or HPV 16/18 partial genotype
      results as well as a histologic biopsy diagnosis from adult women. Manuscripts
      were reviewed for the following: cytology, HPV status, and colposcopy impression
      as well as age, number of women, and number of cervical intraepithelial neoplasia
      (CIN) 2, CIN 3, and cancer cases. Strata were defined by the various combinations
      of cytology, genotype, and colposcopic impression. TABULATION, INTEGRATION, AND
      RESULTS: Of 340 abstracts identified, nine were eligible for inclusion. Data were
      also obtained from three unpublished studies, two of which have since been
      published. We calculated the risk of CIN 2 or worse and CIN 3 or worse based on
      cytology, colposcopy, and HPV 16/18 test results. We found similar risk patterns
      across studies in the lowest risk groups such that risk estimates were similar
      despite different referral populations and study designs. Women with a normal
      colposcopy impression (no acetowhitening), less than high-grade squamous
      intraepithelial lesion cytology, and HPV 16/18-negative were at low risk of
      prevalent precancer. Women with at least two of the following: high-grade
      squamous intraepithelial lesion cytology, HPV16- or HPV18-positive, and high
      grade colposcopic impression were at highest risk of prevalent precancer.
      CONCLUSION: Our results support a risk-based approach to colposcopy and biopsy
      with modifications of practice at the lowest and highest risk levels.

PMID- 30095782
TI  - Role of Bridge Contraception in Postpartum Long-Acting Reversible Contraception
      and Sterilization Fulfillment Rates.
AB  - OBJECTIVE: To estimate the association of bridge contraception with interval long
      acting reversible contraception (LARC) and sterilization fulfillment rates.
      METHODS: This is a secondary analysis of a retrospective single-center cohort
      chart review study examining 1,851 postpartum women who requested LARC or
      sterilization after discharge. Bridge contraception was requested by 597 of these
      women. Primary outcomes included LARC or sterilization fulfillment, time to
      fulfillment, postpartum visit attendance, and pregnancy within 365 days of
      delivery. RESULTS: The rate of LARC or sterilization fulfillment within 90 days
      of delivery was 147 of 597 (24.6%) women using bridge contraception and 287 of
      1,254 (22.9%) women not using bridge contraception (P=.41). After adjusting for
      maternal age, parity, gestational age, mode of delivery, adequacy of prenatal
      care, race-ethnicity, and education level, the use of bridge contraception was
      associated with LARC or sterilization fulfillment (adjusted odds ratio [OR] 1.30,
      95% CI 1.02-1.67). Adequacy of prenatal care and black race was associated with
      fulfillment. The use of bridge contraception was not associated with time to
      fulfillment (adjusted hazard ratio 1.17, 95% CI 0.95-1.44) or postpartum visit
      attendance (adjusted OR 0.97, 95% CI 0.77-1.23). The use of bridge contraception
      was not associated with increased pregnancy within 365 days of delivery (OR 1.00,
      95% CI 0.95-1.05; adjusted OR 0.96, 95% CI 0.73-1.26). CONCLUSION: Bridge
      contraception is associated with increased LARC and sterilization fulfillment
      after postpartum discharge. Long-acting reversible contraception or sterilization
      fulfillment after discharge occurred in less than one in four women. Strategies
      to improve provision of LARC or sterilization before hospital discharge are
      necessary.

PMID- 30095783
TI  - Timing of Delivery in Women With Chronic Hypertension.
AB  - OBJECTIVE: To assess whether routine induction of labor at 38 or 39 weeks in
      women with chronic hypertension is associated with the risk of superimposed
      preeclampsia or cesarean delivery. METHODS: We conducted a retrospective
      population-based study of women with chronic hypertension who had a singleton
      hospital birth at 38 0/7 weeks of gestation of gestation in Ontario, Canada,
      between 2012 and 2016. Women who underwent induction of labor at 38 0/7 to 38 6/7
      weeks of gestation for chronic hypertension (n=281) were compared with those who
      were managed expectantly during that week and remained undelivered at 39 0/7
      weeks of gestation (n=1,606). Separately, women who underwent induction of labor
      at 39 0/7 to 39 6/7 weeks of gestation for chronic hypertension (n=259) were
      compared with women who remained undelivered at 40 0/7 weeks of gestation
      (n=801). RESULTS: Of 534,529 women gave birth during the study period, 6,054
      (1.1%) had chronic hypertension and 2,420 met the inclusion criteria. Women
      managed expectantly at 38 or 39 weeks of gestation were at risk of new-onset
      superimposed preeclampsia (19.2% [308/1,606] and 19.0% [152/801], respectively)
      and eclampsia (0.6% [10/1,606] and 0.7% [6/801], respectively), and more than
      half underwent induction of labor later in gestation (56.8% and 57.8%,
      respectively). The risk of cesarean delivery in the induction groups was lower
      (38 weeks of gestation) or similar (39 weeks of gestation) to that observed in
      women managed expectantly at the corresponding weeks (38 weeks of gestation:
      17.1% vs 24.0%, adjusted relative risk 0.74 [95% CI 0.57-0.95]; 39 weeks of
      gestation: 20.1% vs 26.0%, adjusted relative risk 0.90 [95% CI 0.69-1.17]).
      CONCLUSION: Our findings suggest that in women with isolated chronic
      hypertension, induction of labor at 38 or 39 weeks of gestation may prevent
      severe hypertensive complications without increasing the risk of cesarean
      delivery.

PMID- 30095784
TI  - Rectal Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among Women
      Reporting Anal Intercourse.
AB  - OBJECTIVE: To examine the prevalence and treatment of rectal Chlamydia
      trachomatis and Neisseria gonorrhoeae infections among women reporting receptive
      anal intercourse in a network of sexually transmitted disease or sexual health
      clinics and estimate the proportion of missed infections if women were tested at
      the genital site only. METHODS: We conducted a cross-sectional analysis of C
      trachomatis and N gonorrhoeae test results from female patients reporting
      receptive anal intercourse in the preceding 3 months during visits to 24 sexually
      transmitted disease clinics from 2015 to 2016. Primary outcomes of interest were
      1) anatomic site-specific C trachomatis and N gonorrhoeae testing and positivity
      among women attending selected U.S. sexually transmitted disease clinics who
      reported receptive anal intercourse and 2) the proportion of rectal infections
      that would have remained undetected if only genital sites were tested. RESULTS:
      Overall, 7.4% (3,743/50,785) of women reported receptive anal intercourse during
      the 2 years. Of the 2,818 women tested at both the genital and rectal sites for C
      trachomatis, 292 women were positive (61 genital only, 60 rectal only, and 171 at
      both sites). Of the 2,829 women tested at both the genital and rectal sites for N
      gonorrhoeae, 128 women were positive (31 genital only, 23 rectal only, and 74 at
      both sites). Among women tested at both anatomic sites, the proportion of missed
      C trachomatis infections would have been 20.5% and for N gonorrhoeae infections,
      18.0%. CONCLUSION: Genital testing alone misses approximately one fifth of C
      trachomatis and N gonorrhoeae infections in women reporting receptive anal
      intercourse in our study population. Missed rectal infections may result in
      ongoing transmission to other sexual partners and reinfection.

PMID- 30095785
TI  - An Original Suprapannicular Incision Technique for Cesarean Delivery in the
      Morbidly Obese Parturient.
AB  - BACKGROUND: Obese patients are at an increased risk of cesarean delivery and its
      associated wound complications. We present an alternative incision technique for
      obese parturients that avoids making a Pfannenstiel incision under the panniculus
      while still providing access to the lower uterine segment. TECHNIQUE: For our
      technique, an assistant uses Allis clamps to exert caudal traction on the
      patient's panniculus and a transverse skin incision is made under the umbilicus,
      3 cm below the line joining the anterosuperior iliac crests. On entry to the
      abdominal cavity, a wound retractor is placed to optimize access to the lower
      uterine segment so that a low transverse uterine incision can be made.
      EXPERIENCE: We have used this incision technique on 17 obese patients with no
      incidence of intraoperative complications, no requirement to perform a vertical
      hysterotomy incision, and no postoperative wound infections. CONCLUSION: Our
      technique is a feasible alternative incision for obese parturients that avoids
      making a subpannicular Pfannenstiel incision and still allows for good access to
      the lower uterine segment.

PMID- 30095786
TI  - Prevalence of Maternal Hepatitis C Virus Infection in Ohio.
AB  - OBJECTIVE: To quantify the rising prevalence of maternal hepatitis C virus (HCV)
      infection in Ohio during the peak of the opioid epidemic and to identify maternal
      characteristics and obstetric outcomes associated with maternal HCV infection.
      METHODS: We conducted a population-based retrospective cohort study of all live
      births in Ohio (2006-2015). Frequency of maternal HCV infection as reported on
      birth certificates was compared across each year of the study period. Maternal,
      obstetric, and neonatal characteristics were compared between women with HCV
      infection in pregnancy with those without HCV infection. Multivariate logistic
      regression estimated the relative association between HCV infection and various
      maternal characteristics and obstetric outcomes. RESULTS: During the 10-year
      study period, there were 7,069 reported cases of maternal HCV infection at the
      time of delivery among 1,463,506 (0.5%) live births in Ohio. The rate of maternal
      HCV infection increased 631% between 2006 and 2015, from 1.6 to 11.7 cases per
      1,000 live births (relative risk [RR] 7.6, CI 6.6-8.7, P<.001). After adjusting
      for various confounders, demographic characteristics associated with HCV
      infection included cigarette smoking (adjusted RR 8.6, CI 8.0-9.1), Medicaid
      insurance (adjusted RR 3.6, CI 3.3-3.8), and white, non-Hispanic race (adjusted
      RR 3.2, 95% CI 2.9-3.5). Coinfection during pregnancy with hepatitis B,
      gonorrhea, chlamydia, syphilis, and herpes simplex virus infection was also
      associated with maternal HCV infection. Obstetric and neonatal outcomes
      associated with maternal HCV infection included cesarean delivery, fetal
      intolerance of labor, preterm birth, maternal intensive care unit admission,
      blood transfusion, small for gestational age (less than the 10th percentile),
      neonatal intensive care unit admission, need for assisted neonatal ventilation,
      and infant death. CONCLUSION: Maternal HCV infection has increased more than
      sevenfold over the past decade in Ohio. Our findings highlight a dramatic rise in
      maternal HCV infection that parallels the opioid epidemic within Ohio and in
      neighboring Appalachian states.

PMID- 30095788
TI  - Patient-Clinician Relationships: It's Complicated.

PMID- 30095787
TI  - Laparoscopic Surgical Algorithm to Triage the Timing of Tumor Reductive Surgery
      in Advanced Ovarian Cancer.
AB  - OBJECTIVE: To estimate the effects of a laparoscopic scoring algorithm to triage
      patients with advanced ovarian cancer to immediate or delayed debulking to
      improve complete gross surgical resection rates and determine the resulting
      clinical outcomes. METHODS: We prospectively performed laparoscopic assessment on
      patients with suspected advanced-stage ovarian cancer from April 2013 to December
      2016 to determine primary resectability at tumor reductive surgery. Patients with
      medically inoperable or distant metastatic disease received neoadjuvant
      chemotherapy. Two-surgeon scoring was performed in a blinded fashion using a
      validated scoring method. Patients with predictive index value scores less than 8
      were offered primary surgery and those with scores 8 or greater received
      neoadjuvant chemotherapy. Univariate and multivariate analysis was performed for
      effects on progression-free survival. RESULTS: Six hundred twenty-one patients
      presenting with presumed advanced ovarian cancer were evaluated during the study
      period and 488 patients met inclusion criteria. Two hundred fifteen patients
      underwent laparoscopic scoring, of whom 125 had predictive index value scores
      less than 8 and 84 had predictive index value scores 8 or greater. Blinded two
      surgeon predictive index value scoring resulted in bivariate discordance in only
      2% of patients. Tumor cytoreduction led to no gross residual disease (R0
      resection) in 88% of patients in the primary surgery group and 74% in the
      neoadjuvant chemotherapy group. Patients triaged to primary surgery had an
      improved progression-free survival of 21.4 months versus 12.9 months in those
      patients undergoing neoadjuvant chemotherapy (P<.001). Median progression-free
      survival by treatment group and residual disease status was as follows: primary
      surgery-R0 23.5 months; primary surgery-R1 (any gross residual disease) 17.6
      months; neoadjuvant chemotherapy-R0 15.5 months; and neoadjuvant chemotherapy-R1
      12.9 months (P<.001). On multivariate analysis for progression-free survival,
      baseline CA 125 (P=.001) and gross residual disease at tumor reductive surgery
      (P=.01) were significantly associated with progression-free survival. CONCLUSION:
      Laparoscopic triage assessment allowed for a personalized approach to the
      management of patients with advanced ovarian cancer and resulted in high complete
      surgical resection rates at tumor reductive surgery.

PMID- 30095789
TI  - Letter to Editor: Analysis of Explanted Magnetically Controled Growing Rods From
      Seven UK Spinal Centers.

PMID- 30095790
TI  - Reply to Letter From Drs Nemade, Samdani and Shah Dated 06/4/2018.

PMID- 30095791
TI  - Weekly Teriparatide Administration and Preoperative Anterior Slippage of the
      Cranial Vertebra Next to Fusion Segment < 2 Mm Promote Osseous Union after
      Posterior Lumbar Interbody Fusion.
AB  - STUDY DESIGN: A multicenter case control study. OBJECTIVE: To investigate the
      independent predictors of osseous union after posterior lumbar interbody fusion
      (PLIF). SUMMARY OF BACKGROUND DATA: PLIF is usually performed to treat lumbar
      degenerative diseases in elderly patients. Some patients exhibit intervertebral
      pseudoarthrosis. METHODS: We analyzed 66 elderly patients with osteoporosis who
      underwent PLIF from 2011 to 2014 (all women, mean age 71 years, follow-up period
      >=6 months). Patients were randomly allocated to receive either treatment with
      weekly teriparatide, starting at 1 week postoperatively, or no teriparatide.
      Preoperative lumbar spine radiographs were obtained, and the amount of anterior
      slippage was measured. Osseous union was assessed by computed tomography at 6
      months postoperatively. RESULTS: Thirty-three patients (50%) showed complete
      osseous union, while 33 did not. Teriparatide was administered in 20 (61%)
      patients of the union group and in 9 (27%) patients of the non-union group (P <
      0.01). The preoperative anterior slippage of the cranial vertebra next to fusion
      segment < 2 mm was observed in 16 (49%) and 4 (12%) patients in the union and non
      union groups, respectively (P < 0.01). Multivariate regression analysis showed
      that teriparatide administration (odds ratio, 4.75; 95% confidence interval: 1.51
      14.90; P < 0.01) and preoperative anterior slippage of the cranial vertebra next
      to fusion segment < 2 mm (odds ratio, 5.90; 95% confidence interval: 1.53-22.70;
      P < 0.01) were independently associated with osseous union within 6 months after
      PLIF. At 6 months postoperatively, the mean femoral neck bone mineral density
      significantly increased by 1.1% in the union group and decreased by 1.3% in the
      non-union group (P < 0.05). CONCLUSIONS: Weekly teriparatide administration and
      preoperative anterior slippage of the cranial vertebra next to fusion segment < 2
      mm were independent predictors of osseous union within 6 months after PLIF. Our
      findings suggest that biological and mechanical factors may influence the
      improvement of spinal fusion. LEVEL OF EVIDENCE: 4.

PMID- 30095792
TI  - Quantitative Characteristics of Consecutive Lengthening Episodes in Early Onset
      Scoliosis (EOS) Patients with Dual Growth Rods.
AB  - STUDY DESIGN: A prospective single-center study OBJECTIVE.: To record the
      characteristic forces and lengths observed during distraction episodes in early
      onset scoliosis (EOS), and analyze their interdependencies on the key variability
      among the patients. SUMMARY OF BACKGROUND DATA: The goal of the growing-rod
      technique is to achieve deformity correction alongside maintaining growth of the
      spine. The deformity correction is achieved during the initial surgery but follow
      up distraction episodes are necessary to maintain the growth. The key variables,
      under the control of a surgeon, that affect the growth are the applied
      distraction forces and the distraction lengths. Since the advent of dual growth
      rod technique, there has been many studies exploring the relationship between
      these and the actual growth. However, there is sparse evidence on the actual
      magnitude of distraction forces, and none on its association with patient's
      parameters such as gender, age and deformity. METHODS: In a consecutive series of
      47 patients implanted with dual growth rods, the distraction forces (in N) and
      the lengths (in mm) achieved during each distraction episode and compared against
      the episode specific demographics. The values obtained from each side, i.e.
      concave and convex sides, were averaged to calculate the mean. Statistical
      analysis was performed using t-distribution because for each normalized time
      points (distraction episode). RESULTS: In cumulative, the distraction force
      increased by an amount of 268%, with 120% increase in the early stages
      (distractions episodes 1-6) and 68% increase in the later stages (distractions
      episodes 6-11). Whereas, the cumulative decrease in the length over 11
      distractions episodes was 47%, with 34% and 20% in the early and later stages
      respectively. The study doesn't identify any significant trend with respect to
      gender, age and deformity. CONCLUSION: The distraction force and the length
      increased and decreased respectively with every consecutive distraction episode,
      with no correlation to gender, age, extent of deformity or the extent of
      correction. LEVEL OF EVIDENCE: 5.

PMID- 30095793
TI  - The Impact of Comorbidity Burden on Complications, Length of Stay, and Direct
      Hospital Costs after Minimally Invasive Transforaminal Lumbar Interbody Fusion.
AB  - STUDY DESIGN: Retrospective Cohort OBJECTIVE.: To determine if comorbidity as
      determined by Charlson Comorbidity Index (CCI) is associated with inpatient
      complication rate, length of stay (LOS), or direct hospital costs after minimally
      invasive transforaminal lumbar interbody fusion (MIS-TLIF). SUMMARY OF BACKGROUND
      DATA: In the spine literature, comorbidity burden has been associated with an
      increased risk for complications, prolonged LOS, and greater hospital costs. Few
      studies have investigated the influence of comorbidity burden on these outcomes
      in minimally-invasive spine surgery populations. METHODS: A prospectively
      maintained surgical registry of patients undergoing primary, single-level MIS
      TLIF was retrospectively reviewed. Patients were stratified by CCI and tested for
      association with preoperative demographics and perioperative characteristics
      using chi-squared analysis or one-way analysis of variance for categorical and
      continuous variables, respectively. Complication rates, LOS and direct hospital
      costs were compared between groups were using a one-way analysis of variance.
      RESULTS: 298 patients were included. 19.8% had a CCI of 0, 41.3% had a CCI of 1
      2, 27.2% had a CCI of 3-4, and 11.7% had a CCI >= 5. Elevated CCI was associated
      with older age, smoking, and insurance status. Elevated CCI was significantly
      associated with a greater total inpatient complication rate. Regarding LOS and
      total direct hospital costs, there were no associations identified. However,
      elevated CCI was associated with greater costs accrued in the intensive care
      unit, laboratory costs, and cardiology-related costs. CONCLUSIONS: Greater
      comorbidity burden as reflected by higher CCI scores as a reflection of
      comorbidity burden was associated with increased postoperative complication rates
      following primary, single-level MIS-TLIF. However, this did not lead to
      prolongations in hospital stay or increased total direct hospital costs. This
      lack of association may suggest that the limited tissue trauma and operative
      exposure utilized in minimally invasive approaches may limit the utility of CCI
      as a predictor of surgical outcomes and costs. LEVEL OF EVIDENCE: 4.

PMID- 30095794
TI  - Cervical Alignment of Anterior Cervical Hyperostosis Causing Dysphagia.
AB  - STUDY DESIGN: Retrospective case control study. OBJECTIVE: To investigate whether
      cervical alignment is related to dysphagia in patients with cervical diffuse
      idiopathic skeletal hyperostosis (DISH). SUMMARY OF BACKGROUND DATA: DISH
      involves a wide range of ligamentous ossifications, which can cause dysphagia.
      However, even patients with a high degree of ossification can have only mild
      dysphagia. Dysphagia results from esophageal compression due to ossification;
      however, the exact cause of dysphagia is unknown. METHODS: We reviewed five
      patients with advanced dysphagia due to anterior cervical hyperostosis who
      underwent resection (S group), and five patients with mild symptoms who were only
      monitored (NS group). The patients were evaluated using the Eating Assessment
      Tool-10 (EAT-10) and plain kinetic radiographs of the cervical spine. The O-C2
      angle, M-C angle, C2-7 angle, and C2-6a angle were measured in the flexion,
      neutral, and extension positions. We compared these parameters in the S group
      versus the NS group, and compared the pre- and postoperative values in the S
      group. RESULTS: The EAT-10 score indicated a high degree of dysphagia in the S
      group preoperatively (25 (22-27)) compared with the NS group (1 (1-6)). In the S
      group, the EAT-10 score significantly decreased postoperatively to 1 (0-1), and
      improvement of dysphagia was observed. There was a significant difference between
      the S and NS groups in the DeltaC2-7 and DeltaC2-6a, and between pre- and
      postoperative values in the S group. There were no significant changes in O-C2
      angle and M-C angle, which are parameters of the superior cervical vertebrae.
      CONCLUSIONS: The present results suggest that the restriction of flexion due to
      cervical spine ankylosis may be one of the reasons for dysphagia in patients with
      DISH. LEVEL OF EVIDENCE: 4.

PMID- 30095795
TI  - The Risk Factors of Low Back Pain in Female High-School Students.
AB  - STUDY DESIGN: A prospective cross-sectional study OBJECTIVE.: To evaluate the
      prevalence and associated factors with low back pain (LBP) in female adolescents
      of high school age. SUMMARY OF BACKGROUND DATA: The prevalence of LBP in Tehran
      is high, and the majority of previous studies on LBP in adolescent and its risk
      factors have been performed in the developed countries. Therefore, identification
      of risk factors and planning appropriate protocols for prevention of LBP in
      adolescents may substantially decrease the prevalence of LBP and its burden
      developing countries in future. METHODS: In a prospective cross-sectional study,
      demographic characteristics, including age, body mass index (BMI), weight and
      mode of using backpack, family history of LBP in first degree relatives, and
      passive smoking status of the participants along with a history of LBP were
      recorded. Joint hypermobility was assessed using Beighton scale. Also,
      anthropometric measurements, spinal flexion and hip joint range of motion were
      measured for each participant. RESULTS: In total, 372 students participated in
      the study. The mean (SD) age of the participants was 15.8 (0.9) years. The
      lifetime, more than 3 months, and last month history of LBP was 46.2%, 11.6%, and
      31.2%. Positive history of LBP in the first degree relatives was significantly
      associated with LBP in the participants (p < 0.01). The prevalence of passive
      smoking was significantly higher in the participants with last month history of
      LBP (p = 0.03). The prevalence of joint hypermobility was 15.9% and was
      significantly higher in those with the lifetime and last month history of LBP (p
      < 0.01). CONCLUSIONS: LBP is a common complaint among adolescent and high school
      girl students. The results of this study identified the prevalence and associated
      factors with LBP in high school students and will help develop strategies for
      prevention and treatment of LBP in the adolescent population. LEVEL OF EVIDENCE:
      3.

PMID- 30095796
TI  - Initial Provider Specialty is Associated with Long-term Opiate Use in Patients
      with Newly Diagnosed Low Back and Lower Extremity Pain.
AB  - STUDY DESIGN: Retrospective longitudinal cohort analysis of patients diagnosed in
      2010, with continuous enrollment six months prior to and 12 months following the
      initial visit. OBJECTIVE: To determine whether provider specialty influences
      patterns of opiate utilization long after initial diagnosis. SUMMARY OF
      BACKGROUND DATA: Patients with low back pain present to a variety of providers
      and receive a spectrum of treatments, including opiate medications. The impact of
      initial provider type on opiate use in this population is uncertain. METHODS: We
      performed a retrospective analysis of opiate-naive adult patients in the United
      States with newly diagnosed low back or lower extremity pain. We estimated the
      risk of early opiate prescription (<= 14 days from diagnosis) and long-term
      opiate use (>= six prescriptions in 12 months) based on the provider type at
      initial diagnosis using multivariable logistic regression, adjusting for patient
      demographics and comorbidities. RESULTS: We identified 478,981 newly diagnosed
      opiate-naive patients. Of these, 40.4% received an opiate prescription within one
      year and 4.0% met criteria for long-term use. The most common initial provider
      type was family practice, associated with a 24.4% risk of early opiate
      prescription (95% CI, 24.1-24.6) and a 2.0% risk of long-term opiate use (95% CI,
      2.0-2.1). Risk of receiving an early opiate prescription was higher among
      patients initially diagnosed by emergency medicine (43.1%; 95% CI, 41.6-44.5) or
      at an urgent care facility (40.8%; 95% CI, 39.4-42.3). Risk of long-term opiate
      use was highest for patients initially diagnosed by pain management/anesthesia
      (6.7%; 95% CI, 6.0-7.3) or physical medicine and rehabilitation (3.4%; 95% CI,
      3.1-3.8) providers. CONCLUSION: Initial provider type influences early opiate
      prescription and long-term opiate use among opiate-naive patients with newly
      diagnosed low back and lower extremity pain. LEVEL OF EVIDENCE: 3.

PMID- 30095797
TI  - The Incidence, Clinical Features, and a Comparison Between Early and Delayed
      Onset of Postoperative Spinal Epidural Hematoma.
AB  - STUDY DESIGN: A retrospective observational study OBJECTIVE.: To investigate the
      incidence and clinical features of symptomatic postoperative spinal epidural
      hematoma (PSEH) with regard to spinal level and to compare early and delayed
      onset cases. SUMMARY OF BACKGROUND DATA: PSEH is a serious complication of spinal
      surgeries. The difference in clinical manifestations between early and delayed
      PSEH remains unclear. METHODS: Patients who underwent spinal surgeries between
      1999 and 2013 at our institution, were reviewed through their medical records.
      For patients with PSEH, the incidence, duration to onset, duration from onset to
      evacuation, symptoms, recovery rate (ASIA grade), neurological outcomes ,
      comorbidities, and preoperative use of anticoagulant drugs were examined. We next
      compared patients with early onset PSEH (onset until day 3) vs. delayed onset
      (onset day 4 or later) regarding these clinical factors. RESULTS: Fourteen
      patients (0.42%, 14/3,371) developed symptomatic PSEH. Initial symptoms were
      observed between 0 and 7 days (mean 2.6 +/- 2.4 days) and almost half (43%, 6/14)
      occurred during the delayed phase (mean 5.0 +/- 1.1 days post-surgery). Paralysis
      was the predominant symptom in patients with cervical and thoracic surgeries
      (100%, 6/6), whereas severe pain was most frequent in patients with lumbar
      procedures (63%, 5/8) (p = 0.019). No significant differences were identified
      between early and delayed groups. Neurological outcome was good in 10 cases,
      partial in two cases, and poor in two cases. CONCLUSIONS: The frequency was
      consistent in every spinal region, and the symptoms due to PSEH were correlated
      with spinal level. Almost half the cases were diagnosed after a delay (day 4 or
      later), which supports the necessity to follow up patients with spinal surgeries
      more carefully for a week or so and to educate patients and co-medical staff
      about the possibility of delayed hematoma disorders in order not to defer timely
      intervention. LEVEL OF EVIDENCE: 4.

PMID- 30095798
TI  - The Impact of Vancomycin and Cefazolin as Standard Pre-operative Antibiotic
      Prophylaxis on Surgical Site Infections Following Instrumented Spinal Fusion.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To assess whether
      administration of prophylactic vancomycin, in addition to cefazolin decreased
      revision surgeries for postoperative infection (SSI) as well as the need for
      revisions overall. SUMMARY OF BACKGROUND DATA: In 2010 our institution
      implemented an antibiotic prophylaxis regimen consisting of intravenous
      vancomycin and cefazolin that applied to all patients receiving surgical
      implants. The impact of this change in prophylactic antibiotic regimen on SSIs
      following instrumented spinal fusions remains unknown. METHODS: We conducted a
      pre-post analysis evaluating the effect of the change in antibiotic prophylaxis
      on SSIs following instrumented spinal fusions. We collected data on all eligible
      patients over the course of 2005-2009 prior and 2011-2015. We used logistic
      regression techniques to evaluate unadjusted results for the prophylactic
      antibiotic protocol on all revision surgeries, as well as those for SSI, followed
      by sequential adjustments for sociodemographic factors and surgical
      characteristics. RESULTS: Revision surgeries performed for a diagnosis of
      infection were reduced from a rate of 4% (n = 57) in the period 2005-2009 to 2%
      (n = 44) over 2011-2015 (p < 0.001). At the same time, the incidence of revision
      surgeries for any cause was also reduced (14% in 2005-2009 vs. 9% in 2011-2015; p
      < 0.001). In adjusted analysis, the odds of a revision procedure for SSI were
      reduced by 50% following introduction of the protocol (OR 0.50; 95% CI 0.33,
      0.76). No significant difference in the organisms responsible for SSI were
      identified between 2005-2009 and 2011-2015 (p = 0.22). CONCLUSIONS: This natural
      experiment has shown some utility for a pre-operative prophylactic antibiotic
      regimen of vancomycin and cefazolin, including meaningful reductions in revision
      procedures performed for SSI. This is the first effort we are aware of to
      consider a uniform institutional protocol that employs the use of intravenous
      vancomycin and cefazolin as prophylactic agents. LEVEL OF EVIDENCE: 2.

PMID- 30095799
TI  - PROMIS Physical Function Score Strongly Correlates with Legacy Outcome Measures
      in Minimally Invasive Lumbar Microdiscectomy.
AB  - STUDY DESIGN: Retrospective cohort. OBJECTIVE: This study aims to determine the
      validity of the Patient-Reported Outcomes Measurement Information System (PROMIS)
      Physical Function (PF) in minimally invasive lumbar discectomy (MIS LD) patients.
      SUMMARY OF BACKGROUND DATA: PROMIS was designed to allow for assessment of
      clinical outcomes in fewer questions than previous outcome measures with the goal
      of reducing non-compliance associated with longer, time-consuming surveys.
      However, there exists a paucity of evidence regarding the efficacy of the PROMIS
      PF domain in patients undergoing MIS LD. METHODS: A surgical database of patients
      undergoing 1-3 level MIS LD was retrospectively reviewed. Postoperative changes
      in PROMIS PF scores were analyzed at 6-weeks, 12-weeks, and 6-months using paired
      Student's t-tests. PROMIS scores were compared to Oswestry Disability Index
      (ODI), Visual Analog Scale (VAS) back, and VAS leg scores. Correlations were
      tested using Pearson correlation coefficient. RESULTS: 41 MIS LD patients were
      identified, reporting an average preoperative PROMIS PF score of 35.36 +/- 7.
      Patients demonstrated significant improvement in ODI, VAS back, and VAS leg
      scores. Additionally, strong associations with PROMIS scores were observed for
      preoperative and postoperative ODI (r range: 0.5735 to 0.8543) and postoperative
      VAS back (r range: 0.5332 to 0.6522) and VAS leg pain (r range: 0.5257 to
      0.6412). CONCLUSIONS: Patients undergoing MIS LD demonstrated significant
      improvements in PROMIS PF, ODI, VAS back, and VAS leg pain postoperatively.
      Additionally, improvements in PROMIS physical function scores at each
      postoperative time point were determined to be significantly correlated with ODI,
      VAS back, and VAS leg pain. The results of the current study demonstrate PROMIS
      PF has strong utility as a postoperative outcome assessment tool. LEVEL OF
      EVIDENCE: 4.

PMID- 30095800
TI  - Can Elective Spine Surgery be Performed Safely Among Nonagenarians? Analysis of a
      National Inpatient Database in Japan.
AB  - STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To compare morbidity and
      mortality between nonagenarians and other older adult patients who underwent
      elective spine surgery. SUMMARY OF BACKGROUND DATA: There is a lack of
      information of the perioperative risks of nonagenarians undergoing spine surgery.
      METHODS: Data of patients aged >=65 years who underwent elective spine surgery
      from July 2010 to March 2013 were extracted from the Diagnosis Procedure
      Combination database, a nationwide administrative inpatient database in Japan.
      Clinical outcomes included mortality, occurrence of major complications (cardiac
      events, respiratory complications, pulmonary embolism, stroke, and acute renal
      failure), urinary tract infection, and postoperative delirium. These clinical
      outcomes in nonagenarians were compared with those in patients aged 65 to 79
      years and octogenarians. A multivariate logistic regression model fitted with a
      generalized estimation equation was used to evaluate the influence of advanced
      age on 90-day mortality and postoperative major complications. RESULTS: Of 88,370
      patients identified in the database, 418 were nonagenarians. Compared with
      patients aged 65 to 79 years and octogenarians, nonagenarians had the highest
      rates of 90-day mortality (0.2%, 0.3%, and 1.7%, respectively; p < 0.001) and at
      least one major complication (3.7%, 5.0%, and 7.4%, respectively; p < 0.001).
      Nonagenarians had the highest proportions of cardiac events, respiratory
      complications, urinary tract infections, and delirium. The multivariable logistic
      regression analyses revealed that nonagenarians had increased risks of both 90
      day mortality (odds ratio, 8.65; 95% confidence interval, 3.62-20.6) and
      postoperative major complications (odds ratio, 2.32; 95% confidence interval,
      1.61-3.36) compared with patients aged 65 to 79 years. CONCLUSIONS: Nonagenarians
      had increased morbidity and mortality following elective spine surgery compared
      with other older adult patients. Among the complications, cardiac events,
      respiratory complications, urinary tract infection, and delirium were more likely
      to occur in nonagenarians. LEVEL OF EVIDENCE: 3.

PMID- 30095804
TI  - Development of EMDR in Bosnia and Herzegovina - from an Idea to the First EMDR
      Conference.
AB  - INTRODUCTION: The needs for EMDR (eye movement desensitization and reprocessing)
      treatment of Bosnia-Herzegovina (BH) citizens, affected by 1992-1995 war,
      increased. The Trauma Aid UK (former Humanitarian Assistance Programs UK &
      Ireland) works in partnership with mental health professionals in BH. AIM: We aim
      to build an environment in which qualified and experienced professionals trained
      in EMDR may establish and sustain complete EMDR education and to keep
      international standards of EMDR practice. METHOD: Authors described the history
      of idea and its realization of EMDR education considering all needed phases that
      were provided from the Trauma Aid UK with non profit, humanitarian approach in
      sharing skills of EMDR to mental health therapists in BH. RESULTS: The trainers
      from Trauma Aid UK completed five EMDR trainings in Bosnia-Herzegovina for
      recruited trainees from different cities and entities in BH. For continual
      professional development (CPD) all of these mental health professionals need to
      be active participants in professional and scientific meetings. Though,
      Association of Bosnia and Herzegovina EMDR Therapists, member of EMDR Europe,
      organized the First EMDR conference in Bosnia-Herzegovina sponsored by Trauma Aid
      UK under the patronage of EMDR Association of UK & Ireland. CONCLUSION: Five
      training of Bosnia-Herzegovina mental health workers to effectively use EMDR with
      enthusiastic help of EMDR trainers from Trauma Aid UK resulted with European
      accredited EMDR practitioners, one European accredited EMDR consultant and the
      first EMDR conference in BH. This will keep national development of psychotherapy
      capacities in post-war BH.

PMID- 30095805
TI  - The Syrian Refugees' Need for Trauma-Based Services, a Survey of Mental Health
      Professionals.
AB  - BACKGROUND: Trauma Aid UK (previously HAP UK &Ireland) conducted three EMDR
      trainings in Turkey: the first was in Istanbul on 28thNovember 2013. AIM: The
      purpose of this study is to assess the needs of the Syrian Refugees for trauma
      services training and provision as assesses by mental health professionals who
      work with them. SUBJECTS AND METHODS: Amongst the 62 participants of two Istanbul
      EMDR trainings organised by HAP, 53% were Syrian. We felt it is a unique
      opportunity to assess the needs of Syrian refugees they are working with. We
      asked all the participants who are all mental health professionals to complete an
      Arabic translation of 'The Need for Trauma-based Services Questionnaire' in these
      trainings. The rest of the participants on the course were from Iraq (18%),
      Jordan (16%), Egypt (7%) and others from Palestine, Sudan & Libya (6%). All
      participants completed questionnaires. RESULTS: The results of comparing the
      needs reported by Syrian mental health professionals showed higher prevalence of
      PTSD seen by the Syrian mental health professionals (72% compared with 56% in the
      clients seen by the rest of participants). Also, the Syrian mental health
      professionals could only meet 34% (SD=17.1) of the needs of their client who
      suffer from PTSD. The unmet need for trauma therapy was reported as 100% by these
      professionals. CONCLUSIONS: This study highlighted the high need for trauma
      mental health services of the Syrian refugees as reported by mental health
      professionals working in the neighbouring countries. The needs of the Syrian
      refugees, arriving to the UK because of the very difficult situations, these
      refugees are coming from, may be met with EMDR therapy. EMDR can be used to help
      these refugees to be a productive part of the British society.

PMID- 30095806
TI  - Socio-Demographic Characteristics of Clients Who Were Treated with EMDR Therapy
      in Humanitarian Nongovernmental Organization Islamic Relief World Wide in Bosnia
      and Herzegovina.
AB  - INTRODUCTION: Mental health services after the war 1992-1995 in Bosnia and
      Herzegovina (B-H) are primarily reduced to the public care, though, there are not
      enough professionals in existing conditions, and they are not able to respond to
      cover all the cases. This leaves the room to non governmental organizations (NGO)
      and private mental health care professionals in providing psycho-social services
      to vulnerable populations. Islamic Relief World Wide (IRWW), United Kingdom (UK)
      based humanitarian organisation, whose personal working within Orphans
      department, took part in this mission to contribute B-H citizens wellbeing. IRWW
      in B-H, since 2013 successfully provided psycho-social and EMDR psychotherapy
      services and help throughout its projects primarily designed for orphans, widows
      and socially endangered population. All EMDR therapies were delivered from the
      first author of this presentation. AIM: Our aim is to present socio demographic
      characteristics of clients seeking psychological support and help in IR WW B-H
      who were treated with EMDR therapy. METHODS: We did overview of protocols for the
      clients to whom we helped by using standardised EMDR protocols. RESULTS: In the
      period from 2013 to 2017, we used EMDR protocols for 154 clients: 122 (79.2%)
      were females, 130 (84.4%) were adults (25-56 years old), 21 (13.6%) adolescents
      (13-25 years) and 3 (1.95%) school children. In terms of their socio-economic
      status 54 (35.1%) clients were employed, 42 (27.3%) unemployed and 19 (12.3%)
      from socially endangered category. There were 30 (19.5%) university students, 55
      (35.7%) were with university degree, 63 (40.9%) with high school education, 5
      (3.3%) with primary school. Therapy type (completed, ongoing, incomplete),
      primary complains or reasons for seeking therapy, diagnoses and number of EMDR
      therapy sessions offered, will be addressed too. CONCLUSION: Our results showed
      that EMDR therapy is very useful in helping to B-H population in very difficult
      post-war conditions for the wide varieties of clients.

PMID- 30095807
TI  - The Role of Local Educational Institutions in Educating of EMDR Practitioners in
      Bosnia-Herzegovina.
AB  - INTRODUCTION: Providing good mental health services to the vulnerable and needy
      should be of utmost importance to all mental health professionals. To be able to
      do so, professionals require to be, not only educated but actually properly
      trained and supervised in specially, among various skills, psychotherapy
      orientation. Unlike developed countries, psychotherapy services and professional
      career in psychotherapy in Bosnia and Herzegovina (B&H) is relatively new
      primarily due to the recent historical developments and events in B&H. Besides,
      there is scarcity of professional institutions in B&H which could, not only
      establish structure for, promote but also educate mental health professionals,
      according to the European psychotherapy standards as well as accredit and certify
      psychotherapists, locally or internationally. AIM: The purpose of the present
      study is to show the role of International University of Sarajevo (IUS) as a
      local private educational institution in educating and training EMDR therapist in
      B&H. METHOD: The collaboration between EMDR HAP UK & Ireland, Association of EMDR
      Therapists in Bosnia and Herzegovina (AEMDRTBH), Department of Psychiatry
      University Clinical Center (UCC) Tuzla and Psychiatry Clinic, Clinical Center of
      University (CCU) Sarajevo described with focus on the collaboration with
      International University in Sarajevo. RESULTS: Local institutions in B&H can in a
      variety of ways make a significant contribution to the education and training of
      therapists in BiH in the following ways: providing rooms for realizing of
      education and training and/or conferences (pro bono), promoting EMDR as a
      successful therapeutic method for treating of stress and trauma within relevant
      subjects and programs, providing scholarships for excellent students for EMDR
      education, and in collaboration with local and European EMDR therapists to offer
      EMDR specializations for professionals. Since 2010, one group of therapists has
      been educated and trained by EMDR HAP UK at Department of Psychiatry UCC Tuzla,
      two groups at the Psychiatric Clinic CCU in Sarajevo and one group at IUS. Thanks
      to EMDR HAP UK&Ireland, EMDR therapists in B&H are among the youngest yet very
      efficient and successful therapists who greatly contribute to improving mental
      health of fellow citizens. CONCLUSION: Collaboration between Association of EMDR
      Therapists in Bosnia-Herzegovina, HAP UK & Ireland AP B&H and local educational
      institutions such as IUS can significantly contribute to training efficient
      preparation of EMDR professionals in B&H and help improve overall mental health
      and wellbeing of B&H citizens.

PMID- 30095808
TI  - Self Experience of EMDR Therapy Eficacy - A Case Report.

PMID- 30095809
TI  - Case Study of EMDR Therapy Use in Treating Reproductive Trauma - A Case Report.

PMID- 30095810
TI  - Treating Childbirth Trauma with EMDR - A Case Report.

PMID- 30095811
TI  - EMDR Treatment of a 10 Years Old Boy Who Suffered from Continuous Overnight
      Waking - A Case Report.

PMID- 30095812
TI  - Would the Well-Timed Use of EMDR Therapy in the School System Save the Mental
      Health of Youth? Case Reports.

PMID- 30095814
TI  - EMDR Treatment of Early Trauma Activated by Present Events - A Case Report.

PMID- 30095813
TI  - EMDR Psychotherapy in Work with Youth As Part of the Peacebuilding Activities:
      Case Study of the Interfaith Workshop in Bosnia and Herzegovina - Case Reports.

PMID- 30095815
TI  - EMDR Therapy in Treating Posttraumatic Stress Disorder in Adolescents - A Case
      Report.

PMID- 30095816
TI  - Application of EMDR in the Treatment of Sexual Disfunctionality After
      Histerectomy - A Case Report.

PMID- 30095817
TI  - The Efficiency of EMDR Therapy in Treating Early Multiple Traumas - A Case
      Report.

PMID- 30095818
TI  - EMDR Therapy in Alleviating Psychological Consequences Associated with Childhood
      Maltreatment - A Case Report.

PMID- 30095819
TI  - Mourning after the Loss of a Ten Year Old Son: Unfinished EMDR Therapy with the
      Mother - What We've Achieved and the Challenges for Continuation of the Therapy -
      A Case Report.

PMID- 30095820
TI  - EMDR Treatment Posttraumatic Stress Disorder Caused by Multiple War Trauma - A
      Case Report.

PMID- 30095821
TI  - Aplication of EMDR Therapy in the Treatment of Complicated Patient in Family
      Medicine - A Case Report.

PMID- 30095822
TI  - Integration of EMDR and CBT Techniques in Treatment of Panic Disorder with
      Agoraphobia - A Case Report.

PMID- 30095823
TI  - Phobia Tretman trough the Online Platform - A Case Report.

PMID- 30095824
TI  - Highlights from Faraday Discussion on Designing Nanoparticle Systems for
      Catalysis, London, UK, May 2018.
AB  - The 2018 Faraday Discussion on "Designing Nanoparticle Systems for Catalysis"
      brought together leading scientists to discuss the current state-of-the-art in
      the fields of computational chemistry, characterization techniques, and
      nanomaterial synthesis, and to debate the challenges and opportunities going
      forward for rational catalyst design. The meeting was a vivid discussion of how
      the communities accummulate knowledge and on how innovativeness can be combined
      to have a stronger scientific impact. In the following, we provide an overview of
      the meeting structure, including plenaries, papers, discussion points and
      breakout sessions, and we hope to show, to the wider scientific community, that
      there is great value in continued international discussion and scientific
      collaboration in these fields.

PMID- 30095825
TI  - Sol-gel-derived transparent silica-(Gd,Pr)PO4 glass-ceramic narrow-band UVB
      phosphors.
AB  - Silica-based monolithic transparent glass-ceramics containing (Gd,Pr)PO4
      orthophosphate nanocrystals, prepared by a cosolvent-free sol-gel method,
      efficiently emit narrow-band ultraviolet B (UVB) photoluminescence (PL) at ~313
      nm from the 6P7/2 -> 8S7/2 transition of Gd3+ ions upon excitation into the 4f-5d
      transition of Pr3+ ions. The formation of (Gd,Pr)PO4 nanocrystals as small as ~5
      10 nm facilitates energy transfer between rare-earth (RE) ions while avoiding
      optical loss by Rayleigh scattering. Unlike conventional phosphors, the
      aggregation of Gd3+ ions causes no concentration quenching, and the incorporation
      of inert RE ions to block energy transfer, such as La3+ and Y3+ ions, is
      unnecessary. A glass-ceramic with a Pr3+ ion fraction of 0.02 exhibited the
      maximum internal and external PL quantum efficiencies of ~0.98 and ~0.91,
      respectively, under excitation at 220 nm.

PMID- 30095826
TI  - Electrochemical microfluidics techniques for heavy metal ion detection.
AB  - Heavy metals refer to metals with a density above 5 * 103 kg m-3, such as lead
      (Pb), cadmium (Cd), arsenic (As), and mercury (Hg). Even a trace amount of heavy
      metals is detrimental to human health. With the increasing significance of
      detection of heavy metals, the use of the electrochemical detection technique
      combined with microfluidics is a promising strategy and has thus attracted wide
      attention from academia and is the subject of this review. First, this review
      introduces the basics of electrochemical detection and microfluidics. Second,
      this review presents and evaluates a variety of electrochemical microfluidics
      technologies for heavy metal ions detection that are user friendly, portable,
      inexpensive, and easy to manufacture compared to traditional methods. The
      categorization is based on different detected ions in the order of Pb, Cd, As,
      Hg, Mn, and Zn. Finally, the author summarizes the development of detection
      technology in recent years and puts forward a perspective for the future
      prospects.

PMID- 30095827
TI  - Investigation of the particle size-dependent near-infrared spectral features of
      binary mixture samples in conjunction with Monte Carlo simulation and the
      influence of particle size on the accuracy of quantitative analysis.
AB  - Near-infrared (NIR) spectral features of a target component can be influenced by
      its particle size as well as the particle sizes of the surrounding components in
      multi-component samples; therefore, understanding the essence of particle size
      induced spectral variation is fundamental for robust quantitative analysis. For
      systematic investigation, two different types of binary-component samples were
      prepared. First, in ambroxol/lactose powders, only the particle size of lactose
      (surrounding filler) was varied, while the particle size of ambroxol (a target
      component) remained unchanged. Second, in lactose/PE pellets, the particle size
      of lactose (a target component) was only varied. When measuring ambroxol/lactose
      powders, the absorbances of both ambroxol and lactose peaks were elevated as the
      particle size of lactose increased. The larger lactose particle made the photon
      propagation broader in the sample, so a greater amount of ambroxol was able to
      interact with NIR photons; this led to an increase in absorbance. In the case of
      lactose (10 wt%)/PE pellets, the absorbance of lactose oppositely decreased as
      the lactose particle size increased. Since PE was the dominant component (85-95%)
      and had a small particle size (7 MUm), the depth of photon propagation was
      substantially shallow. In this situation, the larger lactose particles would
      sometimes not be located within the small sampling volume and/or the photons
      would only partially interact with the particles; this led to a decrease in the
      absorbance. For both binary samples, the accuracies for the determination of
      target concentrations deteriorated as the particle size increased. This was due
      to the degradation of the measurement reproducibility caused by the increased
      uncertainty in the photon propagation. Monte Carlo simulation was effective for
      probing the photon propagation inside samples and supportive to explain the
      experimental observations.

PMID- 30095828
TI  - Interface induced magnetic properties of Gd/Co heterostructures.
AB  - Antiferromagnetic coupling between rare-earth and transition metal ferromagnetic
      layers gives rise to various magnetic ground states in heterostructures of these
      materials. Interface structure and morphology tend to play important roles in
      magnetic properties of such systems. Interface induced magnetization in Gd/Co
      heterostructures has been studied using a combination of structural and magnetic
      characterization techniques. The interface morphology of the Gd/Co system was
      varied by growing Gd/Co multilayers using magnetron sputtering under different
      argon partial pressures. Interfacial properties were further modified by
      annealing the multilayers under high vacuum. The macroscopic magnetization
      measurements have been correlated with depth dependent structure and magnetic
      properties of multilayers studied using X-ray and polarized neutron reflectometry
      techniques. Secondary ion mass spectrometry measurements from both as-deposited
      and annealed samples also confirmed modification at the interfaces. It has been
      shown that the interface structure, together with roughness, leads to a unique
      low-temperature magnetic phase characterized by twisting of Gd and Co moments.

PMID- 30095829
TI  - From quantum fragments to Lewis structures: electron counting in position space.
AB  - An electron counting technique that easily provides Lewis structures from real
      space analyses of general wavefunctions is proposed. We base our approach on
      reformulating the adaptive natural density partitioning (AdNDP) algorithm
      proposed by Zubarev and Boldyrev (Phys. Chem. Chem. Phys., 2008, 10, 5207) in
      position space through the use of domain-averaged cumulant densities, which take
      into account many-electron correlations. Averages are performed over the basins
      provided by the quantum theory of atoms in molecules. The decomposition gives
      rise to a set of n-center, two-electron orbitals which describe the dominant
      Lewis structures of a molecular system, and is available both for single- and
      multi-determinant wavefunctions. As shown through several examples, chemically
      intuitive Lewis descriptions are now available from fully orbital invariant
      position space descriptors. In this sense, real space methods are now in a
      position to compete with natural bond order (NBO) orbital procedures without the
      many biases of the latter.

PMID- 30095831
TI  - 2-Picoline catalyst-triggered [2 + 2 + 2] cycloaddition-type reaction of
      acetylenedicarboxylates, aldehydes and alkenes.
AB  - 2-Picoline efficiently catalyzes the formation of alpha,beta-enones from
      acetylenedicarboxylates and aldehydes in the presence of alkenes, thereby leading
      to pyrans in moderate to good yields with complete regioselectivities. This
      synthetic method of pyrans is represented as a first example of catalytic and
      direct [2 + 2 + 2] cycloaddition of three different components under the metal
      free conditions.

PMID- 30095830
TI  - The challenges of characterising nanoparticulate catalysts: general discussion.

PMID- 30095832
TI  - Excitation-dependent electron exchange energy and electron transfer dynamics in a
      series of covalently tethered N,N-bis(4'-tert-butylbiphenyl-4-yl)aniline - [C60]
      fullerene dyads via varying pi-conjugated spacers.
AB  - Femtosecond time-resolved fluorescence and transient absorption studies are
      reported for three newly synthesized covalently linked N,N-bis(4'-tert
      butylbiphenyl-4-yl)aniline (BBA) and pyrrolidinofullerenes (C60)-based donor-pi
      conjugated bridge-acceptor dyads (D-B-A) as functions of the bridge length (7.1,
      9.5 and 11.2 A for Dyad-1, Dyad-2 and Dyad-3), dielectric constants of the medium
      and pump wavelengths. In polar solvent, ultrafast fluorescence quenching (kEET >=
      2 * 1012 s-1) of the BBA moiety upon excitation of the BBA moiety (320 nm) is
      observed in the dyads and is assigned to a mechanism involving electron exchange
      energy transfer (EET) from 1BBA* to C60 followed by electron transfer from BBA to
      1C60*. Cohesive rise and decay dynamics of conjugated BBA+-C60- anion pairs
      confirm the involvement of a distance independent adiabatic charge-separation
      (CS) process (kCS >= 2.2 * 1011 s-1) with near unity quantum efficiency (phiCS >=
      99.7%) and a distance-dependent non-adiabatic charge-recombination (CR) process
      [kCR ~ (1010-108) s-1]. In contrast, excitation of the C60 moiety (lambdaex = 430
      to 700 nm) illustrates photoinduced electron transfer from BBA to 1C60*,
      involving non-adiabatic (diabatic) and distance-dependent CS (kCS in the range of
      0.59-1.78 * 1011 s-1) with 98.86-99.6% (Dyad-3-Dyad-1) quantum efficiency and a
      CR process with kCR values [kCR ~ (1010-108) s-1] up to three orders greater than
      kCS of the respective dyads. Both the processes, CS and CR, upon C60 excitation
      and the CR process upon BBA excitation show distance dependent rate constants
      with exponential factor beta <= 0.5 A-1, and electron transfer is concluded to
      occur through a covalently linked conjugated pi bridge. Global and target
      analysis of fsTA data reveal the occurrence of two closely lying CS states,
      thermally hot (CShot) and thermally relaxed (CSeq) states, and two CR processes
      with two orders of different rate constants. Careful analysis of the kinetic and
      thermodynamic data allowed us to estimate the total reorganization energy and
      electronic coupling matrix (V), which decrease exponentially with distance. These
      novel features of the distance independent adiabatic CS process and the distance
      dependent diabatic CR process upon donor excitation are due to extending the pi
      conjugation between BBA and C60. The demonstrated results may provide a benchmark
      in the design of light-harvesting molecular devices where ultrafast CS processes
      and long-lived CS states are essential requirements.

PMID- 30095833
TI  - Preparation and reactivity of half-sandwich organic azide complexes of osmium.
AB  - Organic azide complexes [Os(eta5-C5H5)(kappa1-N3R)(PPh3){P(OR1)3}]BPh4 (1, 2) [R
      = CH2C6H5 (a), CH2C6H4-4-CH3 (b), CH(CH3)C6H5 (c), C6H5 (d); R1 = Me (1), Et (2)]
      were prepared by allowing bromo-compounds [OsBr(eta5-C5H5)(PPh3){P(OR1)3}] to
      react first with AgOTf and then with an excess of azide in toluene. Benzylazide
      complexes reacted in solution leading to imine derivatives [Os(eta5-C5H5){kappa1
      NH[double bond, length as m-dash]C(R2)Ar}(PPh3){P(OR1)3}]BPh4 (3, 4) [R2 = H (a,
      b), CH3 (c); Ar = C6H5, C6H4-4-CH3; R1 = Me (3), Et (4)]. Phenylazide, on the
      other hand, reacted in solution affording the dinuclear dinitrogen complex
      [{Os(eta5-C5H5)(PPh3)[P(OMe)3]}2(MU-N2)](BPh4)2 (5). Depending on the nature of
      the R substituent, the reaction of the p-cymene complex [OsCl2(eta6-p
      cymene)(PPh3){P(OEt)3}] with RN3 yielded imine [OsCl(eta6-p-cymene){kappa1
      NH[double bond, length as m-dash]C(H)Ar}{P(OEt)3}]BPh4 (6) (Ar = C6H4-4-CH3) and
      amine derivatives [OsCl(eta6-p-cymene)(kappa1-NH2C6H5){P(OEt)3}]BPh4 (7). The
      complexes were characterised spectroscopically (IR, 1H, 31P, 15N NMR) and by the
      X-ray crystal structure determination of [{Os(eta5-C5H5)(PPh3)[P(OMe)3]}2(MU
      N2)](BPh4)2 (5).

PMID- 30095834
TI  - A fluorescent sensor based on aggregation-induced emission: highly sensitive
      detection of hydrazine and its application in living cell imaging.
AB  - Aggregation-induced emission (AIE) molecules eliminate the aggregation-caused
      quenching (ACQ) phenomenon effectively and exhibit excellent properties of a
      fluorescent sensor in the aggregated state. In this paper, an allochroic
      fluorescent sensor based on AIE molecules with a diphenylacrylonitrile structure
      was prepared in high yield by a simple procedure. This molecule possessed good
      AIE properties and exhibited a sensitive sensor ability for aliphatic amines with
      an obvious color change from orange to blue-green. The detailed investigation on
      the detection of hydrazine suggested that the detection limit for hydrazine was
      3.67 * 10-6 M, and the highly sensitive sensor for hydrazine was not influenced
      by other species. The sensor mechanism was confirmed by using 1H NMR and MS
      spectra. The sensor for hydrazine was successfully applied in a test paper,
      exhibiting good practical application potential for detecting hydrazine. The
      experiment of living cell imaging suggested that this sensor showed superior
      bioimaging performance and presented sensitive detection for hydrazine with an
      obvious color change from orange to blue-green.

PMID- 30095836
TI  - Fabrication and high ORR performance of MnOx nanopyramid layers with enriched
      oxygen vacancies.
AB  - Manganese oxide nanopyramids (MONPMs) with enriched oxygen vacancies (OVs) are
      vertically grown on nitrogen doped carbon (NC) microlaminate arrays with narrow
      spacing, yielding a high performance for the oxygen reduction reaction (ORR).

PMID- 30095835
TI  - Anionic cyclometalated Pt(ii) and Pt(iv) complexes respectively bearing one or
      two 1,2-benzenedithiolate ligands.
AB  - Novel anionic cyclometalated Pt(ii) square-planar complexes NBu4[(C^N)PtII(S^S)],
      containing 2-phenylpyridine H(PhPy), 2-(2,4-difluorophenyl)-pyridine H(F2PhPy)
      and benzo[h]quinoline H(Bzq), respectively, as a cyclometalated ligand and the
      dianionic 1,2-benzenedithiolate (Thio)2- fragment as an (S^S) ligand, were
      synthesised. By the simple addition of an equivalent of (Thio)2- to the
      NBu4[(C^N)PtII(Thio)] complexes, octahedral anionic NBu4[(C^N)PtIV(Thio)2]
      analogues were obtained, representing, to the best of our knowledge, the first
      examples of Pt(iv) anionic cyclometalated complexes. The molecular structures of
      the obtained complexes in the case of the NBu4[(Bzq)PtII(Thio)] and the
      NBu4[(Bzq)PtIV(Thio)2] complexes were confirmed by single crystal X-ray
      diffraction analysis. Furthermore, the electrochemical and photophysical
      properties of the two series of Pt(ii) and Pt(iv) newly synthesised complexes
      were studied and DFT and TD-DFT calculations were performed in order to
      comprehensively investigate the displayed behaviour. All Pt(ii) and Pt(iv)
      complexes show intense luminescence in the solid state, with remarkable
      enhancement of the emission quantum yields, proving to be excellent examples of
      aggregation-induced emission systems.

PMID- 30095838
TI  - Semiconductor SERS of diamond.
AB  - In this work, we report a favorable diamond substrate to realize semiconductor
      surface-enhanced Raman spectroscopy (SERS) for trace molecular probes with high
      sensitivity, stability, reproducibility, recyclability and universality. The
      boron-doped diamond (BDD) with surface hydrogenation or oxygenation has matched
      energy levels corresponding to the target molecules and plays a critical role in
      achieving SERS. The enhancement factor based on BDD substrates can reach 104-105,
      which approaches those obtained with most nanostructured compound semiconductors
      and is nearly 3-4 orders of magnitude higher than those of state-of-the-art
      single-element semiconductors (silicon, germanium, and graphene). The mechanism
      of SERS is determined to be charge transfer with vibronic coupling, which could
      enhance the molecular polarizability tensor. Because of its unique properties
      such as chemical inertness, wide bandgap, modulated doping, surface
      functionalization, biocompatibility, and high thermal conductivity, the single
      element semiconductor diamond can serve a high-performance semiconductor SERS
      platform with applications in broad fields.

PMID- 30095837
TI  - Tuning of protease resistance in oligopeptides through N-alkylation.
AB  - N-Methylation of amino acids is an effective way to create protease resistance in
      both natural and synthetic peptides. However, alkyl substituents other than N
      methyl have not been extensively studied. Here, we prepare and examine a series
      of N-substituted peptides in which the size and length of the alkyl group is
      modulated. These design insights provide a unique and modular handle for tuning
      proteolysis in oligopeptides.

PMID- 30095839
TI  - Teratogen screening with human pluripotent stem cells.
AB  - Birth defects are a common occurrence in the United States and worldwide.
      Currently, evaluation of potential developmental toxicants (i.e., teratogens)
      relies heavily on animal-based models which do not always adequately mimic human
      development. In order to address this, researchers are developing in vitro human
      based models which utilize human pluripotent stem cells (hPSCs) to assess the
      teratogenic potential of chemical substances. The field of human developmental
      toxicity assays includes a variety of platforms including monolayer,
      micropattern, embryoid body, and 3D organoid cultures. In this review, we will
      overview the field of human teratogenic assays, detail the most recent advances,
      and discuss current limitations and future perspectives.

PMID- 30095840
TI  - Nonlinear optical responses of self-assembled monolayers functionalized with
      indolino-oxazolidine photoswitches.
AB  - A computational approach combining molecular dynamic simulations and density
      functional theory (DFT) calculations is implemented to evaluate the second-order
      nonlinear optical (NLO) responses of photoresponsive self-assembled monolayers
      (SAMs) based on indolino-oxazolidine molecular switches. These numerical
      simulations provide a complete atomistic picture of the morphology of the SAMs,
      revealing a high degree of positional disorder and an almost isotropic
      orientation of the chromophores. Subsequent DFT calculations, carried out to
      evaluate the average first hyperpolarizability of indolino-oxazolidine switches
      within the SAM, predict that the structural disorder does not significantly
      reduce the NLO contrast compared to that of the isolated molecules. Chromophores
      in the SAM can assume a limited number of specific conformations, due to the high
      rotational barrier that characterize the conjugated bonds along the
      indolino/oxazolidine-dyene-thiophene sequence. A notable exception is the
      rotation about the thiophene-thioalkyl bond, which is not only almost free, but
      also strongly correlated with the magnitude of the first hyperpolarizability.
      Controlling this rotation by chemical design could thus be a viable strategy to
      optimize the SAMs NLO response and the performance of photoresponsive devices
      based on indolino/oxazolidine switches.

PMID- 30095841
TI  - Unravelling the structural rearrangement of polymer colloidal crystals under dry
      sintering conditions.
AB  - The structural rearrangement of polystyrene colloidal crystals under dry
      sintering conditions has been revealed by in situ grazing incidence X-ray
      scattering. The measured diffraction patterns were analysed using distorted wave
      Born approximation (DWBA) theory and the structural parameters of the as-grown
      colloidal crystals of three different particle sizes were determined for the in
      plane and out-of-plane directions in a film. By analysing the temperature
      evolution of the diffraction peak positions, integrated intensities, and widths,
      the detailed scenario of the structural rearrangement of crystalline domains at
      the nanoscale has been revealed, including thermal expansion, particle shape
      transformation and crystal amorphisation. Based on DWBA analysis, we demonstrate
      that in the process of dry sintering, the shape of colloidal particles in a
      crystal transforms from a sphere to a polyhedron. Our results deepen the
      understanding of the thermal annealing of polymer colloidal crystals as an
      efficient route for the design of new nano-materials.

PMID- 30095842
TI  - Enhancement and control of the selectivity in light-driven ketone versus water
      reduction using aminopyridine cobalt complexes.
AB  - Cobalt(ii) complexes with the general structure [CoII(OTf)(Y,XPy2Tstacn)](OTf)
      (1R, where Y,XPy2Tstacn is 1,4-di(p-Y,m-X-picolyl)-7-R-1,4,7-triazacyclononane;
      1H, 1CO2Et, 1DMM) and [CoII(OTf)2(Y,XPyMetacn)] (2R, where Y,XPyMetacn is 1-(p
      Y,m-X-picolyl)-7,4-di-methyl-1,4,7-triazacyclononane; 2CO2Et, 2Cl, 2H, 2DMM,
      2NMe2) were active in both light-driven acetophenone (3a) and water reduction.
      Competition studies show that aromatic ketone/water reduction selectivity ranks
      from 0.2 to 8.0. Nevertheless, considering the concentrations of water and ketone
      in catalysis (ratio H2O/3a ~ 2000) the highest selectivity obtained is greater
      than 15 000. The selectivity correlates well with the CoI/II redox potential
      within the same cobalt catalyst series (span 240 mV (1R) and 290 mV (2R)), with
      electron donating ligands favoring ketone reduction over H2 evolution. Based on
      this finding, the operative mechanism for the reduction of aromatic ketones is
      consistent with a single electron transfer (SET) followed by a hydrogen atom
      transfer (HAT) mechanism. This new insight will be a guide to develop selective
      catalytic systems to produce fine solar chemicals in water.

PMID- 30095844
TI  - High-performance Forster resonance energy transfer-based dye-sensitized
      photocatalytic H2 evolution with graphene quantum dots as the homogeneous energy
      donor.
AB  - A high-performance dye-sensitized photocatalytic H2 evolution system was
      developed based on Forster resonance energy transfer (FRET) by employing water
      soluble and highly photoluminescent N,S codoped graphene quantum dots (NSGQDs) as
      the homogeneous energy donor, erythrosin B (ErB) as the sensentizing dye, and
      platinum nanoparticles (Pt NPs) as the catalyst. NSGQDs absorbed high-energy
      photons that undergo FRET to transfer the excitation energy to the sensitizing
      ErB for maximizing light absorption and also served as an electron transfer and
      loading matrix of Pt NPs for accelarating the electron transfer; as a result, the
      ErB-sensitized NSGQD-Pt system afforded much higher H2 evolution activity than
      the NSGQD-free dye-sensitized system.

PMID- 30095843
TI  - Ionic liquids plus microwave irradiation: a general methodology for the retro
      functionalization of single-walled carbon nanotubes.
AB  - One of the most important objectives nowadays in the field of chemical
      modification of carbon nanotubes (CNTs) is to control the degree of
      functionalization, since excessive modification can disrupt the pi-conjugated
      system and adversely affect their useful properties. Covalent functionalization
      is one of the most common methods for the modification of single-walled carbon
      nanotubes (SWCNTs). However, only a few examples have appeared in the last few
      years regarding the control of the functionalization degree and the reversibility
      of the reaction. We present here an approach for the retro-functionalization of
      SWCNTs which could be applied to different types of covalent functionalizations,
      allowing the restoration of the pi-conjugated structure. The process is performed
      through the combination of ionic liquids plus microwave irradiation and it is
      applicable to the retro-arylation and retro-cycloaddition reactions on SWCNTs.
      The successful retro-functionalization is monitored by Raman spectroscopy,
      thermogravimetric analysis and UV-Vis-NIR spectroscopy.

PMID- 30095845
TI  - A light-triggered transmembrane porin.
AB  - Porins are ideal model systems for channel engineering. OmpG is a robust,
      monomeric, transmembrane beta-barrel without ion selectivity. Here, we present a
      photocaged diethylaminocoumarin (DEACM) hybrid of OmpG. Blockage of the pore by
      DEACM is confirmed by reduced conductivity. An optimal effect was obtained when
      two bulky butyl-substituted coumarin cages were attached on the inside of the
      pore. Irradiation at 385 nm removed the photocages, leading to a restoration of
      channel conductivity.

PMID- 30095846
TI  - Effect of geometry on the dewetting of granular chains by evaporation.
AB  - Understanding evaporation or drying in granular media still remains complex
      despite recent advancements. Evaporation depends on liquid transport across a
      connected film network from the bulk to the surface. In this study, we
      investigate the stability of film networks as a function of the geometry of
      granular chains of spherical grains. Using a controlled experimental approach, we
      vary the grain arrangement or packing and measure the height of the liquid film
      network during evaporation as packing shifts from loose-packed to close-packed
      arrangement. This height can be calculated from an equilibrium between
      hydrostatic pressure and the capillary pressure difference in the vertical film
      network. Following a simulation approach using Surface Evolver, we evaluate the
      pressure variation due to dewetting of the meniscus volume in the grains in both
      the percolating front and evaporating front within the two-phase zone of
      air/water mixture. Results show good agreement between model and experiment. We
      find that above a "critical" packing angle, the liquid continuity is broken and
      films connections fragment into separate, isolated capillary bridges.

PMID- 30095847
TI  - Cell cycle modulation through subcellular spatially resolved production of
      singlet oxygen via direct 765 nm irradiation: manipulating the onset of mitosis.
AB  - Reactive oxygen species, ROS, are acknowledged signaling molecules in cellular
      processes. Singlet molecular oxygen, O2(a1Deltag), is one ROS that can initiate
      cell responses that range from death to proliferation. To better understand the
      mechanisms involved, it is necessary to further investigate cell response to the
      "dose" of O2(a1Deltag) that has been selectively produced at the expense of other
      ROS. In this context, dose refers not just to the amount of O2(a1Deltag)
      produced, but also to the subcellular spatial domain in which it is produced. In
      this study, we selectively produced small and non-toxic amounts of O2(a1Deltag)
      in sensitizer-free experiments by irradiating oxygen at 765 nm using a laser
      focused either into the nucleus or cytoplasm of HeLa cells. We find that
      O2(a1Deltag)-mediated cell proliferation depends appreciably on the site of
      O2(a1Deltag) production. At the same incident laser power, irradiation into the
      cytoplasm elicits moderate enhancement of proliferation, whereas irradiation into
      the nucleus leads to an appreciable delay in the onset and completion of mitosis.
      We discuss these results in light of what is known about the intracellular
      photophysics of O2(a1Deltag) and the redox state of different cell domains.

PMID- 30095848
TI  - Single-molecule force-unfolding of titin I27 reveals a correlation between the
      size of the surrounding anions and its mechanical stability.
AB  - Each cellular protein is surrounded by a biochemical milieu that affects its
      stability and the associated function. The role of this surrounding milieu in the
      proteins' mechanical stability remains largely unexplored. Herein, we report an
      as yet unknown correlation between the size of the surrounding anions and the
      mechanical stability of a protein. Using single-molecule force spectroscopy of
      the 27th domain (I27) of human cardiac muscle protein titin, we show that the
      average unfolding force of the protein decreases with increase in the ionic radii
      of the surrounding anions in the order Cl- > Br- > NO3- > I- > SO42- ~ ClO4-,
      indicating an inverse correlation between anion size and the mechanical stability
      of I27. The destabilizing effect was attributed to the combined effect of
      increase in the unfolding rate constant and unfolding distance upon incubation
      with the anion. These findings reveal that anion size can significantly affect
      the mechanical resistance of proteins and thus could be a convenient and
      promising tool for regulating the mechanical stability of proteins.

PMID- 30095849
TI  - An interlocked flexible piezoresistive sensor with 3D micropyramidal structures
      for electronic skin applications.
AB  - The development of flexible pressure sensors with human-like sensing capabilities
      is an emerging field due to their wide range of applications from human robot
      interactions to wearable electronics. Piezoresistive sensors respond to
      externally induced mechanical stimuli through changes in their electrical
      resistance. The current state-of-the-art piezoresistive sensors are mainly
      constructed via dispersion of conductive nanofillers in an elastomer matrix
      making their performance strongly reliable on the degree of dispersion.
      Alternatively, changes in the contact area of conductive elastomers result in
      higher sensitivity and more tunable variables. Herein, an interlocked sensor
      comprising two flexible layers of 3D pyramidal microstructures is fabricated with
      a thin layer of carbon nanotubes deposited onto the micropatterns. The introduced
      array of micropyramids with varying height and pitch sizes allows for higher
      changes in the contact area upon applying an external load. The results indicate
      that the height and pitch of the structures together with a newly defined
      variable, the critical dimension, affect the sensor's sensitivity. An optimal
      performance is observed for minimized values of the critical dimension.
      Furthermore, to verify the obtained results, a finite-element-assisted analytical
      constriction-resistance model is used to capture the piezoresistive response of
      the sensor. The theoretical results show the high tracking ability of their
      experimental counterparts.

PMID- 30095850
TI  - Many-body depletion forces of colloids in a polydisperse polymer dispersant in
      the long-chain limit.
AB  - We study a system of spherical non-adsorbing particles immersed in a polydisperse
      polymer fluid. We derive an analytic expression for the many-body depletion
      interactions between the colloidal particles in the limit of very long chains. We
      argue that this expression is essentially exact for long chains and justify this
      using explicit simulations. In this way we are able to elucidate the profound
      effect of many-body interactions on the particle thermodynamics. We show that
      using truncated 2-body depletion interactions leads to strong particle
      segregation, while the complete many-body description predicts that the total
      depletion force becomes weak so that the system approximates one which interacts
      via a so-called Kac potential. This implies that the depletion interactions can
      be described using mean-field theory. We show that many-body effects cause a
      significant contraction of the 2-phase region of the particle dispersion. We also
      investigate the system approaching the (tricritical) theta point, which
      terminates the line of first-order critical points of the polymer dispersion in a
      poor solvent and show that many-body effects suppress particle phase transitions.

PMID- 30095851
TI  - Quantification of methylation efficiency at a specific N6-methyladenosine
      position in rRNA by using BNA probes.
AB  - We found that insertion of artificial nucleic acid analogs, such as bridged
      nucleic acid (BNA), into DNA probes increases the difference in melting
      temperature between N6-methyladenosine (m6A)-containing RNA and unmethylated RNA.
      By applying this principle, we quantified methylation efficiency at m6A sites in
      E. coli 23S rRNA with high accuracy.

PMID- 30095852
TI  - Correction: Synthesis of highly substituted 2-spiropiperidines.
AB  - Correction for 'Synthesis of highly substituted 2-spiropiperidines' by Samuel D.
      Griggs et al., Org. Biomol. Chem., 2018, DOI: 10.1039/c8ob01272e.

PMID- 30095853
TI  - Maxillary distraction osteogenesis versus orthognathic surgery for cleft lip and
      palate patients.
AB  - BACKGROUND: Cleft lip and palate is one of the most common birth defects and can
      cause difficulties with feeding, speech and hearing, as well as psychosocial
      problems. Treatment of orofacial clefts is prolonged; it typically commences
      after birth and lasts until the child reaches adulthood or even into adulthood.
      Residual deformities, functional disturbances, or both, are frequently seen in
      adults with a repaired cleft. Conventional orthognathic surgery, such as Le Fort
      I osteotomy, is often performed for the correction of maxillary hypoplasia. An
      alternative intervention is distraction osteogenesis, which achieves bone
      lengthening by gradual mechanical distraction. This review is an update of the
      original version that was published in 2016. OBJECTIVES: To provide evidence
      regarding the effects and long-term results of maxillary distraction osteogenesis
      compared to orthognathic surgery for the treatment of hypoplastic maxilla in
      people with cleft lip and palate. SEARCH METHODS: Cochrane Oral Health's
      Information Specialist searched the following databases: Cochrane Oral Health's
      Trials Register (to 15 May 2018), the Cochrane Central Register of Controlled
      Trials (CENTRAL) (the Cochrane Library, 2018, Issue 4), MEDLINE Ovid (1946 to 15
      May 2018), Embase Ovid (1980 to 15 May 2018), and LILACS BIREME Virtual Health
      Library (Latin American and Caribbean Health Science Information database; from
      1982 to 15 May 2018). The US National Institutes of Health Trials Registry
      (ClinicalTrials.gov) and the World Health Organization International Clinical
      Trials Registry Platform were searched for ongoing trials. No restrictions were
      placed on the language or date of publication when searching the electronic
      databases. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      comparing maxillary distraction osteogenesis to conventional Le Fort I osteotomy
      for the correction of cleft lip and palate maxillary hypoplasia in non-syndromic
      cleft patients aged 15 years or older. DATA COLLECTION AND ANALYSIS: Two review
      authors assessed studies for eligibility. Two review authors independently
      extracted data and assessed the risk of bias in the included studies. We
      contacted trial authors for clarification or missing information whenever
      possible. All standard methodological procedures expected by Cochrane were used.
      MAIN RESULTS: We found six publications involving a total of 47 participants
      requiring maxillary advancement of 4 mm to 10 mm. All of them related to a single
      trial performed between 2002 and 2008 at the University of Hong Kong, but not all
      of the publications reported outcomes from all 47 participants. The study
      compared maxillary distraction osteogenesis with orthognathic surgery, and
      included participants from 13 to 45 years of age.Results and conclusions should
      be interpreted with caution given the fact that this was a single trial at high
      risk of bias, with a small sample size.The main outcomes assessed were hard and
      soft tissue changes, skeletal relapse, effects on speech and velopharyngeal
      function, psychological status, and clinical morbidities.Both interventions
      produced notable hard and soft tissue improvements. Nevertheless, the distraction
      group demonstrated a greater maxillary advancement, evaluated as the advancement
      of Subspinale A-point: a mean difference of 4.40 mm (95% CI 0.24 to 8.56) was
      recorded two years postoperatively.Horizontal relapse of the maxilla was
      significantly less in the distraction osteogenesis group five years after
      surgery. A total forward movement of A-point of 2.27 mm was noted for the
      distraction group, whereas a backward movement of 2.53 mm was recorded for the
      osteotomy group (mean difference 4.8 mm, 95% CI 0.41 to 9.19).No statistically
      significant differences could be detected between the groups in speech outcomes,
      when evaluated through resonance (hypernasality) at 17 months postoperatively (RR
      0.11, 95% CI 0.01 to 1.85) and nasal emissions at 17 months postoperatively (RR
      3.00, 95% CI 0.14 to 66.53), or in velopharyngeal function at the same time point
      (RR 1.28, 95% CI 0.65 to 2.52).Maxillary distraction initially lowered social
      self-esteem at least until the distractors were removed, at three months
      postoperatively, compared to the osteotomy group, but this improved over time and
      the distraction group had higher satisfaction with life in the long term (two
      years after surgery) (MD 2.95, 95% CI 014 to 5.76).Adverse effects, in terms of
      clinical morbidities, included mainly occlusal relapse and mucosal infection,
      with the frequency being similar between groups (3/15 participants in the
      distraction osteogenesis group and 3/14 participants in the osteotomy group).
      There was no severe harm to any participant. AUTHORS' CONCLUSIONS: This review
      found only one small randomised controlled trial concerning the effectiveness of
      distraction osteogenesis compared to conventional orthognathic surgery. The
      available evidence is of very low quality, which indicates that further research
      is likely to change the estimate of the effect. Based on measured outcomes,
      distraction osteogenesis may produce more satisfactory results; however, further
      prospective research comprising assessment of a larger sample size with
      participants with different facial characteristics is required to confirm
      possible true differences between interventions.

PMID- 30095854
TI  - Prevalence and Characteristics of Moderate to Severe Pain among Hospitalized
      Older Adults.
AB  - OBJECTIVES: To investigate the prevalence, characteristics, and management of
      pain in older hospitalized medical patients. DESIGN: Medical record aggregate
      review. SETTING: Tertiary care hospital. PARTICIPANTS: Individuals aged 65 and
      older admitted to the medicine service between November 28, 2014, and May 28,
      2015. MEASUREMENTS: Demographic characteristics, comorbidity burden, pain
      characteristics, and analgesics during index hospitalization were assessed in
      individuals with moderate to severe pain (>=4 on 0-10 Numeric Pain Rating Scale).
      RESULTS: Of 1,267 patients admitted to the medicine service, 248 (20%) had
      moderate to severe pain on admission (mean age 75 +/- 8, 57% female, 50% white).
      During hospitalization, most participants received opioids (80%) and
      acetaminophen (74%), and few received nonsteroidal antiinflammatory drugs (9%).
      Participants with chronic pain had less reduction in pain intensity score from
      admission to discharge than those without a history of chronic pain (mean change
      score 3.7 vs 4.9, p=.002) and were more likely to receive opioids, adjuvant
      analgesics, and other analgesics (all p<.05). CONCLUSION: Twenty percent of older
      adults admitted to a general medicine service had moderate to severe pain.
      Further research about optimal pain management in hospitalized older adults,
      particularly those with chronic pain, is necessary to improve care in this
      population.

PMID- 30095855
TI  - Achieving a Record-High Yield Rate of 120.9 MUgNH3  mgcat.-1  h-1 for N2
      Electrochemical Reduction over Ru Single-Atom Catalysts.
AB  - The electrochemical reduction of N2 into NH3 production under ambient conditions
      represents an attractive prospect for the fixation of N2 . However, this process
      suffers from low yield rate of NH3 over reported electrocatalysts. In this work,
      a record-high activity for N2 electrochemical reduction over Ru single atoms
      distributed on nitrogen-doped carbon (Ru SAs/N-C) is reported. At -0.2 V versus
      reversible hydrogen electrode, Ru SAs/N-C achieves a Faradaic efficiency of 29.6%
      for NH3 production with partial current density of -0.13 mA cm-2 . Notably, the
      yield rate of Ru SAs/N-C reaches 120.9 MUgNH3  mgcat.-1  h-1, which is one order
      of magnitude higher than the highest value ever reported. This work not only
      develops a superior electrocatalyst for NH3 production, but also provides a
      guideline for the rational design of highly active and robust single-atom
      catalysts.

PMID- 30095856
TI  - Cobalt-Nitrogen-Doped Helical Carbonaceous Nanotubes as a Class of Efficient
      Electrocatalysts for the Oxygen Reduction Reaction.
AB  - The oxygen reduction reaction (ORR) is of significant importance in the
      development of fuel cells. Now, cobalt-nitrogen-doped chiral carbonaceous
      nanotubes (l/d-CCNTs-Co) are presented as efficient electrocatalysts for ORR. The
      chiral template, N-stearyl-l/d-glutamic acid, induces the self-assembly of well
      arranged polypyrrole and the formation of ordered graphene carbon with helical
      structures at the molecular level after the pyrolysis process. Co was
      subsequently introduced through the post-synthesis method. The obtained l/d-CCNTs
      Co exhibits superior ORR performance, including long-term stability and better
      methanol tolerance compared to achiral Co-doped carbon materials and commercial
      Pt/C. DFT calculations demonstrate that the charges on the twisted surface of l/d
      CCNTs are widely separated; as a result the Co atoms are more exposed on the
      chiral CCNTs. This work gives us a new understanding of the effects of helical
      structures in electrocatalysis.

PMID- 30095857
TI  - Quantifying the potential of functional evidence to reclassify variants of
      uncertain significance in the categorical and Bayesian interpretation frameworks.
AB  - Additional variant interpretation tools are required to effectively harness
      genomic sequencing for clinical applications. The American College of Medical
      Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP)
      published guidelines for clinical sequence variant interpretation, incorporating
      different types of data that lend varying levels of support towards a benign or
      pathogenic interpretation. Variants of uncertain significance (VUS) are those
      with either contradictory or insufficient evidence, and their uncertainty
      complicates patient counseling and management. Functional assays may provide a
      solution to evidence gaps relegating variants to the VUS category, but the impact
      of functional evidence in this framework has not been assessed. We employ an
      algorithmic analysis of the ACMG/AMP combining rules to assess how the
      availability of strong functional evidence could theoretically improve the
      ability to make a benign or pathogenic assertion. We follow this with analysis of
      actual evidence combinations met by variants through expert curations as part of
      the Clinical Genome Resource (ClinGen). We also examine the impact of functional
      evidence in a Bayesian adaptation of the ACMG/AMP framework. This lays the
      groundwork for an evidence-based prioritization of assay development and variant
      assessment by identifying genes and variants that may benefit the most from
      functional data.

PMID- 30095858
TI  - Low-frequency high-intensity versus medium-frequency low-intensity combined
      therapy in the management of active myofascial trigger points: A randomized
      controlled trial.
AB  - BACKGROUND: Electrotherapeutic modalities have proven to be one of the best
      therapeutic options for myofascial pain syndrome, targeting the myofascial
      trigger points (MTrPs). Combined therapy (CT) is described with paucity in
      literature as the application of ultrasound (US) and electrical stimulating
      current concurrently and at the same site. AIM: The aim was to compare between
      low-frequency, high-intensity burst transcutaneous electrical nerve stimulation
      CT (burst-TENS-CT) and medium-frequency, low-intensity amplitude modulated
      frequency CT (AMF-CT) on upper trapezius active MTrPs (A-MTrPs). PARTICIPANTS AND
      INTERVENTION: In this single-blinded randomized controlled trial design, 70
      participants with acute mechanical neck pain and at least two A-MTrPs in the
      upper trapezius were simply and randomly allocated into three groups-the burst
      TENS-CT, the AMF-CT, or the sham-CT control groups. All groups received three
      sessions per week for four consecutive weeks. OUTCOME MEASURES: Outcome measures
      included pressure pain threshold (PPT) using a digital electronic algometer and
      active cervical lateral flexion range of motion (ROM) using an iPhone Clinometer
      application. Data were collected prior to the first treatment and at the end of
      the 4-week trial. RESULTS: There were statistically significant improvements in
      postintervention PPT and ROM values in both treatment groups (p < 0.0001). As for
      the sham-US, no significant difference was found between the preintervention and
      postintervention values (p > 0.05). Bonferroni correction test revealed that
      there was a significant difference between all the three groups (p < 0.0001).
      Additionally, burst-TENS-CT yields a greater increase in PPT and ROM values (547%
      and 49.32%, respectively) than that of medium-frequency AMF-CT. CONCLUSION:
      Within the scope of this study, both CT modalities were effective in increasing
      PPT and cervical lateral flexion ROM. Nonetheless, low-frequency, high-intensity
      burst-TENS-CT was shown to be superior over the medium-frequency, low-intensity
      AMF-CT in terms of reducing pain sensitivity and increasing ROM.

PMID- 30095859
TI  - Desire for Sterilization Reversal Among U.S. Females: Increasing Inequalities by
      Educational Level.
AB  - CONTEXT: For decades, high reliance on female sterilization in the United States
      has been accompanied by a high level of desire for sterilization reversal, and
      less-educated women have been more likely than better educated women to use the
      method and desire a reversal. Little is known about how levels of and educational
      differentials in such desire have changed in recent decades. METHODS: Data from
      4,147 women who reported being sterile from a tubal sterilization in the 1995,
      2002 and 2006-2010 waves of the National Survey of Family Growth were analyzed
      using chi-square and Wald tests and binary logistic regression analyses.
      Predicted probabilities were calculated to determine the likelihood of desire for
      procedure reversal by wave and educational level. RESULTS: The prevalence of
      desire for sterilization reversal rose by 41%, from 18% in 1995 to 23% in 2002
      and 25% in 2006-2010. Overall, women with a bachelor's degree were less likely
      than those who had not finished high school to desire a reversal (odds ratio,
      0.2), and this educational differential was larger in 2006-2010 than in earlier
      waves. Predicted probabilities indicate that 9% of sterilized women with less
      than a high school education and 8% of those with a bachelor's degree expressed a
      desire for procedure reversal in 1995, as did 15% and 3%, respectively, in 2006
      2010. CONCLUSION: Future research should consider how insurance coverage of all
      methods under the Affordable Care Act may affect use of sterilization and desire
      for reversal.

PMID- 30095860
TI  - Evolved Gas Analysis-Mass Spectrometry to Identify the Earliest Organic Binder in
      Aegean Style Wall Paintings.
AB  - An organic binder was identified in the painted fragments from the Canaanite
      palace of Tel Kabri, Israel. Recently dated to the late 18th century B.C.E. by 14
      C, Tel Kabri is the most ancient of the Eastern Mediterranean sites in which
      Aegean style paintings have been found. The application of pigments was suspected
      to be using an organic binding medium, particularly for the Egyptian Blue
      pigment. Samples of blue paint were examined using evolved gas analysis-mass
      spectrometry (EGA-MS) in order to overcome the analytical challenges imposed by
      highly degraded aged proteinaceous materials. Egg was identified as the binder
      based on the presence of hexadecanonitrile and octadecanonitrile, confirming the
      use of a secco painting technique. Lysozyme C from Gallus gallus was detected by
      proteomics analysis, confirming the presence of egg. To our knowledge, this is
      the earliest use of egg as a binder in Aegean style wall paintings.

PMID- 30095861
TI  - The Distribution of Essential, Trace, and Nonessential Minerals in Weanling Male
      Rats Fed Sheep or Cow Milk.
AB  - SCOPE: The aim of the study is to determine the effects of sheep milk consumption
      in comparison to cow milk on the mineral distribution in the soft organs and
      serum in a growing animal model system. As the mineral composition of cow and
      sheep milk differs, different effects on the bio-accumulations in the body may be
      observed. Differences in the mineral composition of cow and sheep milk may lead
      to different bioavailability or accumulation of minerals in the body. Newly
      weaned rats were fed either cow milk, sheep milk, or sheep milk diluted so that
      it had the same solid content as cow milk. At the end of the feeding trial, the
      concentration of minerals in the organs and plasma of the rats was assessed. The
      results indicate that the consumption of the high level of minerals in sheep milk
      does not have any negative effects in the rat model. METHODS AND RESULTS: Newly
      weaned male rats were fed ad libitum for 28 days on either cow milk, sheep milk,
      or sheep milk diluted to have the same concentration of milk solids as cow milk.
      Animals were euthanized and the soft organs and serum were harvested and then
      analyzed for mineral composition by inductively coupled plasma MS. Rats fed sheep
      milk had lower iron concentrations in the liver and higher concentrations of
      rubidium and cesium in all of the soft organs. The growth rate of the rats was
      not affected by the type of milk consumed. CONCLUSION: The concentration of
      essential and trace minerals in the liver is found to be significantly different
      between rats fed sheep milk compared to those fed cow milk (p < 0.05). The
      consumption of sheep milk does not affect the growth of animals.

PMID- 30095862
TI  - Decision-making about cervical screening in a heterogeneous sample of
      nonparticipants: A qualitative interview study.
AB  - OBJECTIVE: According to the precaution adoption process model, cervical screening
      nonparticipants represent a heterogeneous group including those who are unaware
      of, unengaged with, or undecided about screening, as well as intenders and
      decliners. We aimed to explore beliefs about cervical screening among these
      different types of nonparticipant. METHODS: Semistructured interviews were
      carried out with women aged 26 to 65 years living in Britain (n = 29). Women were
      purposively sampled to represent different nonparticipant types. Interviews were
      transcribed verbatim, and data were analysed thematically using framework
      analysis. RESULTS: The salience of some barriers to screening varied between
      different types of nonparticipant. Bad experiences were prominent in the
      discussions of women who had decided not to attend, while practical barriers were
      more prominent among intenders. There was also some overlap between
      nonparticipant types. For example, many of the undecided women described not
      wanting to go for screening, but with less certainty than decliners. Some
      intenders (particularly those who had not been screened before) described not
      really wanting to attend but feeling they ought to. Women's views on the
      invitation/reminder process also varied; intenders and maintainers appreciated
      written reminders and general practitioner (GP) prompts but decliners sometimes
      perceived these as "badgering." Throughout the interviews, women described
      changing views on screening in the wider context of ageing and motherhood.
      CONCLUSIONS: The salience of screening barriers varies by nonparticipant type,
      offering possibilities for tailored interventions. However, the fluidity of
      women's stage of screening adoption might have implications for this approach to
      intervention design.

PMID- 30095863
TI  - Biomaterials for intervertebral disc regeneration: Current status and looming
      challenges.
AB  - A biomaterial-based strategy is employed to regenerate the degenerated
      intervertebral disc, which is considered a major generator of neck and back pain.
      Although encouraging enhancements in the anatomy and kinematics of the
      degenerative disc have been gained by biomaterials with various formulations in
      animals, the number of biomaterials tested in humans is rare. At present, most
      studies that involve the use of newly developed biomaterials focus on
      regeneration of the degenerative disc, but not pain relief. In this review, we
      summarise the current state of the art in the field of biomaterial-based
      regeneration or repair for the nucleus pulposus, annulus fibrosus, and total disc
      transplantation in animals and humans, and we then provide essential suggestions
      for the development and clinical translation of biomaterials for disc
      regeneration. It is important for researchers to consider the commonly neglected
      issues instead of concentrating solely on biomaterial development and
      fabrication.

PMID- 30095864
TI  - Complete lymph node dissection or observation in melanoma patients with multiple
      positive sentinel lymph nodes: A single-center retrospective analysis.
AB  - Although the role of sentinel lymph node biopsy (SLNB) as a prognostic factor is
      well established, its consequences for therapy are controversial. The aim of this
      study was to analyze if complete lymph node dissection (CLND) in patients with
      more than one positive sentinel lymph node (SLN) significantly improves melanoma
      specific survival (MSS) and progression-free survival (PFS). Medical records of
      patients who underwent SLNB between 2001 and 2016 at the University Hospital of
      Cologne were reviewed, and patients with positive SLN were identified. Patient
      and tumor characteristics, patterns of recurrence, progression-free and melanoma
      specific survival were analyzed. Seventy-eight patients with multiple positive
      and 197 patients with one positive SLN were included in this study. Patients with
      multiple positive SLN had significantly more positive non-SLN compared with
      patients with only one positive SLN (26.9% vs 8.6%, P = 0.01). However, in the
      subgroup of patients with multiple positive SLN, CLND did not significantly
      improve MSS (mean MSS 95 vs 75 months, P = 0.5) and PFS (mean PFS 59 vs 68 months
      P = 0.167). CLND did not result in a significant improvement in PFS and MSS in
      patients with multiple positive SLN.

PMID- 30095865
TI  - Diagnosis and outcome in nonhydropic fetal pleural effusions.
AB  - OBJECTIVE: To determine the outcome of all pregnancies with nonhydropic fetal
      pleural effusions in the Wessex region. METHOD: Data were extracted from the
      Wessex congenital anomaly database for the years 1994-2015 inclusive. RESULTS:
      Sixty-two fetuses and babies were identified giving a total prevalence of 1:9500.
      Eight fetuses had bilateral effusions with additional, nonhydrops anomalies, and
      54 had isolated effusions. Of the isolated cases, 36 presented before 24-week
      gestation: 12 were unilateral and 24 bilateral. All of the unilateral effusions
      resolved before or soon after birth with no other diagnosis but of the bilateral
      cases, four (17%) had a trisomy and three (13%) a genetic or syndrome diagnosis.
      Eighteen isolated cases presented after 24-week gestation, six were unilateral of
      which one had trisomy 21 (17%), and three (50%) Noonan's or another lymphoedema
      syndrome. Twelve were bilateral: One had trisomy 21, one an unbalanced
      translocation (17%), three had Noonan's or another lymphoedema syndrome, and two
      an unspecified syndrome (42%) at birth. CONCLUSION: These data suggest that a
      chromosomal microarray should be offered to all fetuses presenting with a pleural
      effusion in the absence of hydrops, and Noonan's syndrome testing should be
      considered for those that develop after 24 weeks. AIM: To determine the outcome
      of all pregnancies with nonhydropic fetal pleural effusions in the Wessex region
      from 1994-2015.

PMID- 30095866
TI  - The role of mononuclear phagocytes in Ebola virus infection.
AB  - The filovirus, Zaire Ebolavirus (EBOV), infects tissue macrophages (Mphis) and
      dendritic cells (DCs) early during infection. Viral infection of both cells types
      is highly productive, leading to increased viral load. However, virus infection
      of these two cell types results in different consequences for cellular function.
      Infection of Mphis stimulates the production of proinflammatory and
      immunomodulatory cytokines and chemokines, leading to the production of a
      cytokine storm, while simultaneously increasing tissue factor production and thus
      facilitating disseminated intravascular coagulation. In contrast, EBOV infection
      of DCs blocks DC maturation and antigen presentation rendering these cells unable
      to communicate with adaptive immune response elements. Details of the known
      interactions of these cells with EBOV are reviewed here. We also identify a
      number of unanswered questions that remain about interactions of filoviruses with
      these cells.

PMID- 30095867
TI  - Reproductive success of soybean (Glycine max L. Merril) cultivars and exotic
      lines under high daytime temperature.
AB  - The objectives were to (a) quantify the effects of high daytime temperature (HDT)
      from gametogenesis to full bloom on photosynthesis and pod set in soybean
      (Glycine max L. Merril) genotypes and (b) assess the relationships among
      photosynthesis, cardinal temperatures for pollen germination, in vitro pollen
      germination percentage, canopy reflectance, and pod-set percentage. Three field
      experiments were conducted, and Experiment I had HDT between gametogenesis and
      full bloom (36.5 degrees C to 38.6 degrees C) compared with Experiments II and
      III (29.5 degrees C to 31.6 degrees C; optimum temperature). HDT decreased
      photosynthesis (22%) and pod-set percent (11%) compared with Experiment III.
      Cultivars had higher photosynthesis and pod-set percent than plant introduction
      (PI) lines. The cultivars (i.e., IA3023 and KS4694) and PI lines (i.e., PI393540
      and PI588026A) were HDT tolerant and susceptible, respectively. The decreased pod
      set percentage in susceptible genotypes (PI lines) was associated with pollen
      characteristics. Significant positive (r2  >= 0.67) association between
      photosynthesis, cardinal temperatures for pollen germination (Topt and Tmax )
      with pod-set percentage was observed. However, a negative (r2  >= -0.43)
      association between photosynthesis and pod set with canopy reflectance at visible
      spectrum was observed. In vitro pollen germination and canopy reflectance at
      visible spectrum can be used as a high-throughput phenotypic tool for breeding
      HDT-tolerant genotypes.

PMID- 30095869
TI  - Time to Nurture Better Services.
AB  - More government funding has been promised to increase specialist mental
      healthcare for mothers in the perinatal period but this is just part of the
      action required, writes Claire Read.

PMID- 30095868
TI  - Pediatric Retinal Diseases.

PMID- 30095870
TI  - Clouds, Silver Linings and Storm Desmond.
AB  - University Hospitals of Morecambe Bay Foundation Trust had done its homework on
      preparing for emergencies but, even so, Storm Desmond tested the organization to
      its limits, as Helen Mooney discovered.

PMID- 30095871
TI  - How much training in ultrasound would emergency nurses need?
AB  - Ultrasound sonography, in which a high-pitched sound wave travels at different
      speeds through objects of variable density, offers effective clinical diagnostic
      applications to identify problems, such as free abdominal fluid following blunt
      trauma, cardiac effusion and long bone fractures.

PMID- 30095872
TI  - An Epic outcome.
AB  - How one emergency department achieved a 70% rise in patients receiving life
      saving sepsis treatment within an hour.

PMID- 30095873
TI  - Why creating a framework is worth the effort.
AB  - You have an idea and know roughly what you want to say, but you need a plan. the
      simplest plan is a beginning, a middle and an end. Whether your article is 300
      words or 3,000, it should start with an indication of its purpose. Build it with
      supporting evidence or argument and conclude in a way that encourages readers to
      pause and reflect.

PMID- 30095874
TI  - Emergency management of burns: part 2.
AB  - Infrequent presentation of this patient group to emergency departments can cause
      stress and anxiety to front-line clinicians when they are faced with patients
      with a traumatic burn injury. Assessment relies on accurate evaluation of burn
      aetiology, size and depth, and initial management is directly responsible for
      patients' outcomes and quality of life. This is the second article in a two-part
      series that gives an overview of the minimum standard of care in burns first aid,
      and highlights the likely challenges in assessment of burn depth and size. The
      aim of the two articles is to enhance emergency clinicians' knowledge and
      confidence in burn management, and to build awareness of the life-changing
      implications of the initial clinical interventions in burn care.

PMID- 30095875
TI  - Research Abstracts Digital Dentistry.

PMID- 30095876
TI  - Dento-Legal Implications in Digital Dentistry.

PMID- 30095877
TI  - Clinical Examination and Record-Keeping: Electronic Records.

PMID- 30095879
TI  - We're Going Digital: The Current State of CAD/CAM Dentistry in Prosthodontics.
AB  - This paper reviews the current state of computer-aided design and manufacturing
      (CAD/CAM) in dentistry, with a special focus on restorative dental applications.
      The potential, advantages, and limitations of the technology will be discussed,
      comparing the digital workflow to conventional techniques, based on contemporary
      clinical evidence. The technology does seem to offer a more streamlined and
      efficient means of treatment planning and delivery of care through reduced
      chairside time, with reported improved patient satisfaction. Nonetheless, the
      accuracy and treatment outcomes of CAD/CAM treatment modalities are inconsistent
      and do not support a superior performance to existing conventional techniques,
      rather a comparable one.

PMID- 30095878
TI  - Digital Transformation in Dentistry: An Organisational View.

PMID- 30095880
TI  - Clinical Photography: A Self Help Guide.

PMID- 30095881
TI  - Powder and Powder-Free Intra-Oral Scanners: Digital Impression Accuracy.
AB  - Aim: The purpose of this study was to evaluate the accuracy of digital
      impressions taken with two different intra-oral scanners (with and without
      optical powder), by dentists with different level of experience. Material and
      Methods: Two intra-oral scanning devices (Apollo DI and Cerec Omnicam, Sirona
      Dental GmbH, Germany) were used to obtain a digital cast from scanning different
      preparations on a maxillary typodont. Three operator groups scanned five crown
      preparations using both powder and powder-free scanning systems. One group
      consisted of fourth year dental students, a second group consisted of
      prosthodontic residents, and third group consisted of prosthodontic specialists.
      The precision of spray application and impression expertise was compared between
      the three groups. Results: The most frequently encountered errors were non-linear
      powder application, inappropriate intra-oral scanner manipulation, and
      insufficient digital data for crown fabrication. Conclusion: Experience is needed
      in order to achieve high quality digital impressions. A prosthodontic specialist
      avoided incorrect manipulation of an intra-oral camera, uneven application of
      powder spray and achieved a better marginal fit.

PMID- 30095882
TI  - New frontiers in Dental Technology: An Overview.
AB  - The pace of technological advance across science is staggeringly fast. Our
      ability to translate some of the potential developments in technology into
      concepts/products/devices that can assist dentists in caring for patients is key
      to ensuring that both the profession and the people we care for derive full
      benefit from these new technologies. This overview will focus in four areas:
      research and how we gather and interpret data to inform health care; the
      diagnosis and prevention of disease; planning care; and new concepts in terms of
      achieving desired health outcomes for patients. Some of the technological
      advances will be in their infancy and others close to or indeed clinical reality.
      The objective of this overview is to show where we are in terms of the cutting
      edge of technology and to whet the appetite for things to come.

PMID- 30095884
TI  - Radiation Protection: Getting to Grips With the Changes.

PMID- 30095883
TI  - Utilising Digital Dentistry for the Management of Patients With Hypodontia of
      Lateral Incisers.
AB  - Management of missing maxillary lateral incisors can involve joint restorative
      and orthodontic treatment planning and intervention. Digital dental technologies
      are contributing to better communication and precision of planning both between
      clinicians and patients and within specialists. This paper outlines the ways in
      which digital dentistry is facilitating this process with a focus on
      restoratively-driven treatment planning and delivery.

PMID- 30095885
TI  - Revealing the Relationship between Energy Level and Gas Sensing Performance in
      Heteroatom-Doped Semiconducting Nanostructures.
AB  - The cation substitutional doping of metal oxide semiconductors plays pivotal
      roles in improving the gas sensing performances, but the doping effect on surface
      sensing reaction is still not well understood. In this study, indium oxides doped
      with various heteroatoms are investigated to obtain in-depth understanding of how
      doping (or the resulting change in the electronic structure) alters the surface
      absorbed oxygen chemistry and subsequent sensing process. The experimental
      results reveal that energy level of In2O3 can be modulated by introduction of
      these dopants, some of which (e.g., Al, Ga, and Zr) lead to the elevation of
      Fermi level, whereas others (e.g., Ti, V, Cr, Mo, W, and Sn) bring about relative
      drop in Fermi level. However, only the former can improve the response to
      formaldehyde, indicating a strong link between Fermi level and sensing
      properties. Mechanistic study suggests that the elevation of Fermi level
      increases energy level difference between oxide semiconductor and oxygen
      molecules and facilitates the surface absorption of oxygen species, resulting in
      superior formaldehyde sensing activity. Especially, Al-doped In2O3 exhibits
      remarkably enhanced sensing performances toward formaldehyde at low working
      temperature (150  degrees C) with high response, good selectivity, ultralow limit
      of detection (60 ppb), and short response time (2-23 s). Our findings not only
      promote the understanding of sensing reaction process and its correlation with
      the semiconductor electronic structure but also offer a general guideline for
      large-scale screening of promising oxide semiconductor-based sensing materials
      for gas detection.

PMID- 30095886
TI  - Highly Effective Removal of Nonsteroidal Anti-inflammatory Pharmaceuticals from
      Water by Zr(IV)-Based Metal-Organic Framework: Adsorption Performance and
      Mechanisms.
AB  - Nonsteroidal anti-inflammatory pharmaceuticals are emerging organic
      micropollutants in surface water, groundwater, and wastewater, whose removal is
      very important yet challenging. As a new class of porous functional materials,
      metal-organic frameworks (MOFs) have attracted extensive attention for their
      adsorption applications. Here, we report that Zr(IV)-based MOFs (defective UiO
      66, and MOF-808) have extraordinary adsorption ability to remove nonsteroidal
      anti-inflammatory pharmaceuticals from water. Excellent adsorption performances
      are obtained for UiO-66 and MOF-808, particularly for UiO-66, of which the
      adsorption capacities are the highest in a wide series of adsorptive materials
      previously reported. It is elucidated that the incomplete-coordinated cationic Zr
      in the cluster has high affinity for the anionic pharmaceutical (chemical
      adsorption) and that the adsorption interaction between the benzene ring of the
      pharmaceutical and MOF's ligand is involved to enhance or as an alternative to
      the adsorption interactions (pi-pi interaction). In particular, adsorption of
      ibuprofen, ketoprofen, naproxen, indomethacin, and furosemide by UiO-66 and MOF
      808 and the synergetic effect of chemical adsorption and pi-pi interaction are
      outstanding, leading to extremely higher binding energies ( Ebind) and sorption
      abilities.

PMID- 30095887
TI  - Coordination-Mediated Synthesis of 67Ga-Labeled Purification-Free Trivalent
      Probes for in Vivo Imaging of Saturable Systems.
AB  - A large excess of unlabeled ligands over gallium-67 (67Ga) provides 67Ga-labeled
      probes with high radiochemical yields in a short reaction time. However, the
      unlabeled ligands hinder target accumulation of radiolabeled probes by competing
      for target molecules. To circumvent the problem, we investigated the way to
      prepare 67Ga-labeled multivalent probes from monovalent ligands. The reaction of
      a bi- or tridentate ligand with [67Ga]Ga-citrate resulted in 67Ga-labeled probes
      of insufficient stability. However, the reaction of [67Ga]Ga-citrate with a
      mixture of RGD-conjugated salicylaldehyde and triamine provided a 67Ga-labeled
      trivalent probe with stability sufficient for in vivo applications. Since the
      free Schiff base ligand decomposed rapidly upon injection, the 67Ga-labeled
      trivalent probe visualized the murine tumor without postlabeling purification,
      which was not achieved with a 67Ga-labeled trivalent probe from a trivalent
      ligand. These findings indicate the availability of Schiff base ligands to
      prepare 67Ga-labeled trivalent probes by a simple radiolabeling procedure.

PMID- 30095888
TI  - A Dual-Band Multilayer InSe Self-Powered Photodetector with High Performance
      Induced by Surface Plasmon Resonance and Asymmetric Schottky Junction.
AB  - A dual-band self-powered photodetector (SPPD) with high sensitivity is realized
      by a facile combination of InSe Schottky diode and Au plasmonic nanoparticle (NP)
      arrays. Comparing with pristine InSe devices, InSe/Au photodetectors possess an
      additional capability of photodetection in visible to near-infrared (NIR) region.
      This intriguing phenomenon is attributed to the wavelength selective enhancement
      of pristine responsivities by hybridized quadrupole plasmons resonance of Au NPs.
      It is worth pointing out that the maximum of enhancement ratio in responsivity
      reaches up to ~1200% at a wavelength of 685 nm. In addition, owing to a large
      Schottky barrier difference formed between active layer and two asymmetric
      electrodes, the responsivities of dual-band InSe/Au photodetector could reach up
      to 369 and 244 mA/W at the wavelength of 365 and 685 nm under zero bias voltage,
      respectively. This work would provide an additional opportunity for developing
      multifunctional photodetectors with high performance based on two-dimensional
      materials, upgrading their capacity of photodetection in a complex environment.

PMID- 30095889
TI  - Understanding the Role of Minor Molybdenum Doping in LiNi0.5Co0.2Mn0.3O2
      Electrodes: from Structural and Surface Analyses and Theoretical Modeling to
      Practical Electrochemical Cells.
AB  - Doping LiNi0.5Co0.2Mn0.3O2 (NCM523) cathode material by small amount of Mo6+
      ions, around 1 mol %, affects pronouncedly its structure, surface properties, and
      electronic and electrochemical behavior. Cathodes comprising Mo6+-doped NCM523
      exhibited in Li cells higher specific capacities, higher rate capabilities, lower
      capacity fading, and lower charge-transfer resistance that relates to a more
      stable electrode/solution interface due to doping. This, in turn, is ascribed to
      the fact that the Mo6+ ions tend to concentrate more at the surface, as a result
      of a synthesis that always includes a necessary calcination, high-temperature
      stage. This phenomenon of the Mo dopant segregation at the surface in NCM523
      material was discovered in the present work for the first time. It appears that
      Mo doping reduces the reactivity of the Ni-rich NCM cathode materials toward the
      standard electrolyte solutions of Li-ion batteries. Using density functional
      theory (DFT) calculations, we showed that Mo6+ ions are preferably incorporated
      at Ni sites and that the doping increases the amount of Ni2+ ions at the expense
      of Ni3+ ions, due to charge compensation, in accord with X-ray absorption fine
      structure (XAFS) spectroscopy measurements. Furthermore, DFT calculations
      predicted Ni-O bond length distributions in good agreement with the XAFS results,
      supporting a model of partial substitution of Ni sites by molybdenum.

PMID- 30095890
TI  - The Recognition of Unrelated Ligands by Identical Proteins.
AB  - Unrelated ligands, often found in drug discovery campaigns, can bind to the same
      receptor, even with the same protein residues. To investigate how this might
      occur, and whether it might be typically possible to find unrelated ligands for
      the same drug target, we sought examples of topologically unrelated ligands that
      bound to the same protein in the same site. Seventy-six pairs of ligands, each
      bound to the same protein (152 complexes total), were considered, classified into
      three groups. In the first (31 pairs of complexes), unrelated ligands interacted
      largely with the same pocket residues through different functional groups. In the
      second group (39 pairs), the unrelated ligand in each pair engaged different
      residues, though still within the same pocket. The smallest group (6 pairs)
      contained ligands with different scaffolds but with shared functional groups
      interacting with the same residues. We found that there are multiple chemically
      unrelated but physically similar functional groups that can complement any given
      local protein pocket; when these functional group substitutions are combined
      within a single molecule, they lead to topologically unrelated ligands that can
      each well-complement a site. It may be that many active and orthosteric sites can
      recognize topologically unrelated ligands.

PMID- 30095891
TI  - High-Efficiency White Organic Light-Emitting Diodes Integrating Gradient Exciplex
      Allocation System and Novel D-Spiro-A Materials.
AB  - How to maintain high power efficiency (PE) and color stability under operating
      brightness is critical for the white organic light-emitting diodes (WOLEDs). To
      this end, two novel spiro-type materials STPy3 and STPy4 were designed. These
      materials could act as a single host and achieve a remarkable external quantum
      efficiency of 27.5% at 1000 cd m-2; to further optimize the PEs of OLEDs, STPy3/4
      and PO-T2T were used as co-host-induced exciplexes, which enhanced the PE of
      green OLED to over 148.0 lm W-1. Unfortunately, the lower triplet energy level of
      exciplexes than blue emitters implied it is commonly unsuitable to fabricate
      WOLEDs. Herein, a new allocation of gradient exciplex (AGE) strategy was
      developed in which the formed excitons could be rationally allocated in a
      consequently doped nonuniform profile. The AGE incorporated the advantages of the
      exciplex with an ultralow turn-on voltage of 2.3 V and efficiency stability of
      spiro materials. The PE at 1000 cd m-2 was enhanced to 72.7 lm W-1, representing
      the first exciplex WOLED with the performance exceeding that of conventional
      fluorescent tubes.

PMID- 30095892
TI  - Novel Zeolite-5A@MOF-74 Composite Adsorbents with Core-Shell Structure for H2
      Purification.
AB  - Hydrogen is considered as one of the most important clean and renewable energy
      sources for a sustainable energy future. However, its efficient and cost
      effective purification still remains challenging. In this work, we report the
      development of novel zeolite@metal-organic framework (MOF) composites comprised
      of MOF-74 and zeolite-5A with core-shell structure for efficient purification of
      H2. The composites were synthesized hydrothermally through the addition of
      zeolite particles with and without carboxyl functional groups to the MOF
      synthesis solution. The zeolite/MOF weight ratio was varied systematically to
      find the optimum composition based on the adsorption performance. The formation
      of zeolite@MOF composites was confirmed by various characterization techniques.
      Single-component adsorption isotherms of CO2, CO, CH4, N2, and H2 over composites
      were measured at 25  degrees C to determine their equilibrium adsorption
      capacity. It was found that the zeolite-5A@MOF-74 with weight ratio of 5:95
      exhibited a similar morphology to that of pristine MOF-74, but with higher
      surface area and total pore volume. Moreover, this composite showed 20-30%
      increase in CO2, CO, CH4, and N2 uptake than the bare MOF, which could be
      attributed to the formation of new mesopores at the MOF-zeolite interface. The
      estimated selectivity values for CO2/H2, CO/H2, CH4/H2, and N2/H2 were higher
      than those of the zeolite and/or MOF. Our results also indicated that surface
      modification of zeolite prior to composite formation does not enhance the
      adsorption capacities of the composites. Overall, the findings of this study
      suggest that the zeolite-5A@MOF-74 composites with core-shell structure are
      promising candidates for industrial H2 purification processes.

PMID- 30095893
TI  - Increased N,N-Dimethyl Leucine Isobaric Tag Multiplexing by a Combined Precursor
      Isotopic Labeling and Isobaric Tagging Approach.
AB  - Multiplex isobaric tags have become valuable tools for high-throughput
      quantitative analysis of complex biological samples in discovery-based proteomics
      studies. Hybrid labeling strategies that pair stable isotope mass difference
      labeling with multiplex isobaric tag-based quantification further facilitate
      these studies by greatly increasing multiplexing capability. In this work, we
      present a cost-effective chemical labeling approach that couples duplex stable
      isotope dimethyl labeling with our custom 12-plex N,N-dimethyl leucine (DiLeu)
      isobaric tags in a combined precursor isotopic labeling and isobaric tagging
      (cPILOT) strategy that is compatible with a wide variety of biological samples
      and permits 24-plex quantification in a single LC-MS/MS experiment. We
      demonstrate the utility of the DiLeu cPILOT approach by labeling yeast digests
      and performing proof-of-principle quantification experiments on the Orbitrap
      Fusion Lumos.

PMID- 30095894
TI  - Locating Carbon-Carbon Double Bonds in Unsaturated Phospholipids by Epoxidation
      Reaction and Tandem Mass Spectrometry.
AB  - The presence of carbon-carbon double bonds (C?Cs) in unsaturated phospholipids is
      closely related to lipid conformations and physiochemical activities. Previously,
      we have demonstrated that epoxidation reaction facilitated by low-temperature
      plasma (LTP) enabled the structural analysis of unsaturated fatty acids (FAs).
      Epoxidation of the C?C leads to the production of an epoxide, which can be easily
      cleaved via collision-induced dissociation (CID) to produce diagnostic ions
      indicative of the C?C bond locations in FAs. In this work, we further developed
      this method for analysis of phospholipids. Tandem mass spectrometry analysis with
      epoxidation reaction was performed in both positive and negative ion mode to
      analyze phosphatidylcholines (PCs), phosphatidic acids (PAs),
      phosphatidylethanolamines (PEs), phosphatidylglycerols (PGs), and
      phosphatidylinositols (PIs). The developed method was applied in a shotgun
      lipidomics approach to characterize phospholipids in a bovine liver extract.

PMID- 30095895
TI  - Postsynthetic Metalation Metal-Organic Framework as a Fluorescent Probe for the
      Ultrasensitive and Reversible Detection of PO43- Ions.
AB  - The self-assembly of a zinc salt with the novel ligand 4,4',4"-[(1,3,5-triazine
      2,4,6-triyl)tris(sulfanediyl)]tribenzoic acid generated 3D microporous metal
      organic frameworks (MOFs), namely, {[Zn4(L3-)2(O2-)(H2O)2].4EtOH} n. The
      frameworks with multiple Lewis basic sites exhibit easily sensitized properties.
      After encapsulation of the Tb3+ cation in this Zn-MOF, the as-obtained
      fluorescent-functionalized Tb@Zn-MOFs not only maintain distinguished chemical
      stabilities but also exhibit strong characteristic emissions of trivalent terbium
      ions. Interestingly, Tb@Zn-MOF has been chosen to be a potential highly selective
      and sensitive luminescent platform for the reversible detection of PO43- ions in
      aqueous and living cell buffer solutions with a fast response time of 10 s and a
      low detection limit (0.1 ppm). Strikingly, this work presents the first example
      of a fluorescent sensor that can quantitate PO43- in simulated biological fluids
      and monitor these ions in the water system in a wide range of concentrations from
      10-6 to 10-3 M.

PMID- 30095896
TI  - Identification of Unknown Brominated Bisphenol S Congeners in Contaminated Soils
      as the Transformation Products of Tetrabromobisphenol S Derivatives.
AB  - Compared with tetrabromobisphenol A (TBBPA) and its derivatives, the skeletally
      similar chemicals tetrabromobisphenol S (TBBPS) and its derivatives have been
      rarely studied, and very little is known about their structures, environmental
      occurrence, and behaviors. In this study, a total of 84 soil samples from a
      chemical industrial park have been collected and analyzed to investigate the
      occurrence of TBBPS and its derivatives and to identify novel TBBPS analogs.
      TBBPS, TBBPS bis(2,3-dibromopropyl ether) (TBBPS-BDBPE), and three byproducts,
      TBBPS mono(allyl ether) (TBBPS-MAE), TBBPS mono(2-bromoallyl ether) (TBBPS-MBAE),
      and TBBPS mono(2,3-dibromopropyl ether) (TBBPS-MDBPE), have been detected with
      contents ranging from below detection limits to 1934.6 ng/g dw and with detection
      frequencies of 21.4-97.6%. In addition, another 5 unknown TBBPS analogs,
      tribromobisphenol S (TriBBPS), 2,2',6'-TriBBPS-MAE (TriBBPS-MAE3.2), 2,6,2'
      TriBBPS-MAE (TriBBPS-MAE3.4), 2',6'-DBBPS-MAE (DBBPS-MAE2.0), and 2,6-DBBPS-MAE
      (DBBPS-MAE2.6), have been identified in these soil samples by untargeted mass
      spectrometry screening. These unknown analogs have also been observed in
      laboratory transformation experiments of TBBPS-MDBPE conducted under reducing
      conditions. TriBBPS-MAE3.4 and DBBPS-MAE2.6 were more likely to be produced than
      TriBBPS-MAE3.2 and DBBPS-MAE2.0 due to the stereoselectivity of the
      transformation. TriBBPS-MAE3.4 and DBBPS-MAE2.0 were more stable, resulting in
      higher detection frequencies of these compounds in soil samples. Ether bond
      breakage and debromination contributed to the generation of these novel products.
      The results provide new information on the behaviors of TBBPS and its derivatives
      in the environment.

PMID- 30095897
TI  - Development of Multifunctional Molecules as Potential Therapeutic Candidates for
      Alzheimer's Disease, Parkinson's Disease, and Amyotrophic Lateral Sclerosis in
      the Last Decade.
AB  - Neurodegenerative diseases pose a substantial socioeconomic burden on society.
      Unfortunately, the aging world population and lack of effective cures foreshadow
      a negative outlook. Although a large amount of research has been dedicated to
      elucidating the pathologies of neurodegenerative diseases, their principal causes
      remain elusive. Metal ion dyshomeostasis, proteopathy, oxidative stress, and
      neurotransmitter deficiencies are pathological features shared across multiple
      neurodegenerative disorders. In addition, these factors are proposed to be
      interrelated upon disease progression. Thus, the development of multifunctional
      compounds capable of simultaneously interacting with several pathological
      components has been suggested as a solution to undertake the complex pathologies
      of neurodegenerative diseases. In this review, we outline and discuss possible
      therapeutic targets in Alzheimer's disease, Parkinson's disease, and amyotrophic
      lateral sclerosis and molecules, previously designed or discovered as potential
      drug candidates for these disorders with emphasis on multifunctionality. In
      addition, underrepresented areas of research are discussed to indicate new
      directions.

PMID- 30095899
TI  - Polycaprolactone Nanofibers Containing Vascular Endothelial Growth Factor
      Encapsulated Gelatin Particles Enhance Mesenchymal Stem Cell Differentiation and
      Angiogenesis of Endothelial Cells.
AB  - During the regeneration of tissues and organs, growth factors (GFs) play a vital
      role by affecting cell behavior. However, because of the low half-life time and
      quick degradation of GFs, their stimulations on cells are relatively short and
      discontinuous. In this study, a releasing scaffold platform, consisting of
      polycaprolactone (PCL) nanofibers and vascular endothelial growth factor (VEGF)
      encapsulated gelatin particles, was developed to extend the influence of GFs on
      mesenchymal stem cells (MSCs) and endothelial cells (ECs). The results showed
      that this kind of scaffold can direct the differentiation of MSCs to ECs and
      maintain the stability of the tubular structure, an indicator of the angiogenesis
      ability of ECs, for an extended period of time. Therefore, the results suggest
      the potential application of PCL/VEGF-encapsulated gelatin particles (PCL/VGPs)
      as a growth factor (GF)-releasing scaffold platform in vascular tissue
      engineering.

PMID- 30095898
TI  - Effects of Agronomic Management and Climate on Leaf Phenolic Profiles, Disease
      Severity, and Grain Yield in Organic and Conventional Wheat Production Systems.
AB  - Agricultural intensification over the last 40 years has increased cereal yields,
      but there is very limited information on the effects of intensification practices
      (e.g., nondiverse rotations, mineral NPK fertilizer, and pesticides) on crop
      health and quality. Results from the study reported here suggest that the use of
      mineral NPK fertilizers reduces phenolic acid and flavonoid concentrations in
      leaves and increases the susceptibility of wheat to lodging and powdery mildew,
      when compared to composted FYM inputs. In contrast, the use of herbicides,
      fungicides, and growth regulators reduces lodging and foliar disease severity but
      had no effect on phenolic acid and flavonoid concentrations. The use of composted
      FYM inputs also resulted in a significant grain yield reduction and not
      substantially reduced the severity of opportunistic pathogens such as Septoria,
      which remain a major yield limiting factor unless fungicides are used and/or more
      Septoria resistant varieties become available.

PMID- 30095900
TI  - Potent and Orally Bioavailable Inverse Agonists of RORgammat Resulting from
      Structure-Based Design.
AB  - Retinoic acid receptor related orphan receptor gammat (RORgammat), has been
      identified as the master regulator of TH17-cell function and development, making
      it an attractive target for the treatment of autoimmune diseases by a small
      molecule approach. Herein, we describe our investigations on a series of 4-aryl
      thienyl acetamides, which were guided by insights from X-ray cocrystal
      structures. Efforts in targeting the cofactor-recruitment site from the 4-aryl
      group on the thiophene led to a series of potent binders with nanomolar activity
      in a primary human-TH17-cell assay. The observation of a DMSO molecule binding in
      a subpocket outside the LBD inspired the introduction of an acetamide into the
      benzylic position of these compounds. Hereby, a hydrogen-bond interaction of the
      introduced acetamide oxygen with the backbone amide of Glu379 was established.
      This greatly enhanced the cellular activity of previously weakly cell-active
      compounds. The best compounds combined potent inhibition of IL-17 release with
      favorable PK in rodents, with compound 32 representing a promising starting point
      for future investigations.

PMID- 30095901
TI  - Concentration-Dependent, Membrane-Selective Activity of Human LL37 Peptides
      Modified with Collagen Binding Domain Sequences.
AB  - Antimicrobial peptides (AMPs) such as LL37 are promising alternatives to
      antibiotics to treat wound infections due to their broad activity,
      immunomodulatory functions, and low likelihood of antimicrobial resistance. To
      deliver LL37 to chronic wounds, we developed two chimeric LL37 peptides with C
      terminal collagen binding domains (CBD) derived from collagenase ( cCBD-LL37) and
      fibronectin ( fCBD-LL37) as a strategy for noncovalent tethering of LL37 onto
      collagen-based, commercially available wound dressings. The addition of CBD
      sequences to LL37 resulted in differences in cytotoxicity against human
      fibroblasts and antimicrobial activity against common wound pathogens. In this
      study, we sought to determine the sequence-, structure-, and concentration
      dependent properties underlying these differences in bioactivity. Molecular
      dynamics (MD) simulations allowed visualization of the structure of each peptide
      and calculation of residue-level helicity, revealing that residues within the CBD
      domains were not helical. Circular dichroism (CD) spectroscopy affirmed that the
      overall structures of LL37 and each CBD-LL37 peptide was primarily helical
      (greater than 67%) in a membrane-like solvent. Quartz crystal microbalance with
      dissipation (QCM-D) and imaging of fluorescent bilayers revealed unique,
      concentration-dependent interactions of each peptide with bilayers of different
      lipid compositions. Specifically, fCBD-LL37, which is less cytotoxic than LL37
      and cCBD-LL37, demonstrated higher affinity toward anionic bilayers (model
      bacterial cell membranes) than zwitterionic bilayers (model mammalian cell
      membranes). In contrast, cCBD-LL37 and LL37 demonstrated similar affinities to
      both types of bilayers. This study demonstrates that the combination of MD, CD,
      and QCM-D may enable predictive modeling of the effects of primary sequence
      alterations on peptide secondary structure and membrane interactions.
      Understanding the structural and mechanistic properties of AMPs and their
      interactions with specific lipid bilayer compositions may enable the engineering
      of less cytotoxic AMPs with improved therapeutic indexes for human wound healing
      applications.

PMID- 30095903
TI  - AARON: An Automated Reaction Optimizer for New Catalysts.
AB  - We describe an open-source computational toolkit (AARON: An Automated Reaction
      Optimizer for New catalysts) that automates the quantum mechanical geometry
      optimization and characterization of the transition state and intermediate
      structures required to predict the activities and selectivities of asymmetric
      catalytic reactions. Modern computational quantum chemistry has emerged as a
      powerful tool for explaining the selectivity and activity of asymmetric
      catalysts. However, reliably predicting the stereochemical outcome of realistic
      reactions often requires the geometry optimization of hundreds of transition
      state and intermediate structures, which is a tedious process. AARON automates
      these optimizations through an interface with a popular electronic structure
      package, accelerating quantum chemical workflows to enable the computational
      screening of potential catalysts. AARON is built using a collection of object
      oriented Perl modules (AaronTools) that provide functionality to build and modify
      molecular and supramolecular structures. The main functionalities of AaronTools
      are also available as stand-alone command-line scripts. The core features of
      AaronTools and AARON are explained, and representative applications of AARON to
      both organocatalyzed and transition-metal-catalyzed reactions are presented.

PMID- 30095902
TI  - Influence of a Dietary Vegetable Oil Blend on Serum Lipid Profiles in Large
      Yellow Croaker ( Larimichthys crocea).
AB  - Serum lipid metabolic responses are associated with certain metabolic disorders
      induced by dietary habits in mammals. However, such associations have not been
      reported in fish. Lipidomic analyses were performed to investigate fish lipid
      metabolic responses to a dietary vegetable oil (VO) blend and to elucidate the
      mechanism of how the dietary VO blend affects serum lipid profiles. Results
      showed that the dietary VO blend strongly affects serum lipid profiles,
      especially the ratio of triglyceride/phosphatidylcholine (TAG/PC), via inhibiting
      hepatic PC biosynthesis and facilitating hepatic and intestinal lipoprotein
      assembly. Studies in vitro suggested that changes of serum TAG/PC ratio may be
      partially attributed to altered fatty acid composition in diets. Additionally,
      the reduction of 16:0/18:1-PC induced by the dietary VO blend may play a role in
      abnormal lipid deposition through inhibiting PPARA-mediated activation of beta
      oxidation. These findings suggested that the serum TAG/PC ratio might be a
      predictive parameter for abnormal lipid metabolism induced by dietary nutrition
      in fish.

PMID- 30095904
TI  - Tailoring the Substitution Pattern on 1,3,5-Triazine for Targeting Cyclooxygenase
      2: Discovery and Structure-Activity Relationship of Triazine-4
      Aminophenylmorpholin-3-one Hybrids that Reverse Algesia and Inflammation in Swiss
      Albino Mice.
AB  - Here, we report analgesic and anti-inflammatory activity of a series of compounds
      obtained by appending 4-aminophenylmorpholin-3-one and acyclic, cyclic, or
      heterocyclic moieties on 1,3,5-triazine. The structures of compounds 4b and 6b
      are optimized for the best inhibition of COX-2 with IC50 values of 0.06 and 0.08
      MUM, respectively, and selectivity over COX-1 of 166 and >125, respectively. At
      the dose of 5 mg kg-1, these compounds significantly reduced acetic acid induced
      writhings, and their ED50 values were found to be 2.2 and 1.9 mg kg-1,
      respectively. Besides the cell-based and animal-based experiments showing the
      modes of action of these compounds targeting COX-2, the interaction behavior of
      4b with COX-2 was also characterized, with physicochemical experiments including
      ITC, NMR, UV-vis, and molecular-modeling studies. Characteristically, these
      compounds interact with R120, Y355, and W385, the residues responsible for
      holding the substrate and mediating the process of electron transfer during the
      metabolic phase of the enzyme.

PMID- 30095905
TI  - Performance of Engineered Streambeds for Inducing Hyporheic Transient Storage and
      Attenuation of Resazurin.
AB  - Several U.S. programs provide financial incentives for stream restoration to
      improve degraded water quality. These efforts prioritize hyporheic zone (HZ)
      restoration to enhance contaminant attenuation, but no stream restoration or
      stormwater best management practice (BMP) explicitly tailors hyporheic residence
      times to target specific contaminants of concern. Here we present the first
      physical demonstration of a new BMP called Biohydrochemical Enhancements for
      Streamwater Treatment (BEST). BEST are subsurface modules that use hydraulic
      conductivity modifications to drive hyporheic exchange and control residence
      times, combined with reactive geomedia to increase HZ reaction rates. Experiments
      were conducted in 15-m long outdoor flumes: one all-sand control, the other with
      BEST modules. Sodium chloride (conservative tracer) and resazurin (surrogate for
      a reactive pollutant) injections were conducted, with observations analyzed by
      stream transient storage models. Results demonstrated that BEST increased the
      effective HZ size and resazurin transformation both by ~50% compared to the
      control. Numerical simulations of extended reach lengths showed that BEST could
      achieve 1-log removal of resazurin in 111 m, versus 172 m in the control, and 414
      m and 683 m in two numerically simulated urban streams. These results emphasize
      the potential of BEST as a novel HZ BMP to improve streamwater quality.

PMID- 30095906
TI  - Improved Antibacterial Activity of the Marine Peptide N6 against Intracellular
      Salmonella Typhimurium by Conjugating with the Cell-Penetrating Peptide Tat11 via
      a Cleavable Linker.
AB  - The poor penetration ability of antimicrobial agents limits their use in the
      treatment of intracellular bacteria. In this study, the conjugate CNC (6) was
      generated by connecting the cell-penetrating peptide Tat11 (1) and marine peptide
      N6 (2) via a cathepsin-cleavable linker, and the C-terminal aminated N6 (7) and
      CNC (8) were first designed and synthesized to eliminate intracellular
      Salmonellae Typhimurium. The cellular uptake of 6 and stability of 7 were higher
      than those of 2, and conjugates 6, 8, and 7 had almost no hemolysis and
      cytotoxicity. The antibacterial activities of 6, 8, and 7 against S. Typhimurium
      in RAW264.7 cells were increased by 67.2-76.2%, 98.6-98.9%, and 96.3-97.6%,
      respectively. After treatment with 1-2 MUmol/kg of 6, 8, or 7, the survival of
      the S. Typhimurium-infected mice was 66.7-100%, higher than that of 2 (33.4
      66.7%). This result suggested that 6, 8, and 7 may be excellent candidates for
      novel antimicrobial agents to treat intracellular pathogens.

PMID- 30095907
TI  - Self-Healing pH- and Enzyme Stimuli-Responsive Hydrogels for Targeted Delivery of
      Gemcitabine To Treat Pancreatic Cancer.
AB  - A novel, multifunctional hydrogel that exhibits a unique set of properties for
      the effective treatment of pancreatic cancer (PC) is presented. The material is
      composed of a pentablock terpolypeptide of the type PLys- b-(PHIS- co-PBLG)-PLys-
      b-(PHIS- co-PBLG)- b-PLys, which is a noncytotoxic polypeptide. It can be
      implanted via the least invasive route and selectively delivers gemcitabine to
      efficiently treat PC. Simply mixing the novel terpolypeptide with an aqueous
      solution of gemcitabine within a syringe results in the facile formation of a
      hydrogel that has the ability to become liquid under the shear rate of the
      plunger. Upon injection in the vicinity of cancer tissue, it immediately reforms
      into a hydrogel due to the unique combination of its macromolecular architecture
      and secondary structure. Because of its pH responsiveness, the hydrogel only
      melts close to PC; thus, the drug can be delivered directionally toward the
      cancerous rather than healthy tissues in a targeted, controlled, and sustained
      manner. The efficacy of the hydrogel was tested in vivo on human to mouse
      xenografts using the drug gemcitabine. It was found that the efficacy of the
      hydrogel loaded with only 40% of the drug delivered in one dose was equal to or
      slightly better than the peritumoral injection of 100% of the free drug delivered
      in two doses, the typical chemotherapy used in clinics so far. This result
      suggests that the hydrogel can direct the delivery of the encapsulated drug
      effectively in the tumor tissue. Enzymes lead to its biodegradation, avoiding
      removal by resection of the polypeptidic carrier after cargo delivery. The unique
      properties of the hydrogel formed can be predetermined through its molecular
      characteristics, rendering it a promising modular material for many biological
      applications.

PMID- 30095909
TI  - Differential Antibody Responses to Outer Membrane Proteins Contribute to
      Differential Immune Protections between Live and Inactivated Vibrio
      parahemolyticus.
AB  - It is widely accepted that live vaccines elicit higher immune protection than
      inactivated vaccines. However, the mechanisms are largely unknown. Here, an array
      with 64 recombinant outer membrane proteins of Vibrio parahemolyticus was
      developed to explore antibody responses of live and inactivated V.
      parahemolyticus post immunization of the 8th, 12th, 16th and 20th day. Among the
      64 outer membrane proteins, 28 elicited antibody generation. They were all
      detected in live vaccine-induced immunity but only 15 antibodies were found in
      inactivated vaccine-induced immunity. Passive immunization showed that higher
      percent survival was detected in live than inactivated vaccine-induced
      immunities. Active immunization indicated that out of 19 randomly selected outer
      membrane proteins, 5 stimulated immune protection against V. parahemolyticus
      infection. Among them, antibodies to VP2309 and VPA0526 were shared in mice
      immunized by live or inactivated vaccines, whereas antibodies to VPA0548,
      VPA1745, and VP1667 were only found in mice immunized by live vaccine. In
      addition, live V. parahemolyticus stimulated earlier antibody response than
      inactivated bacteria. These results indicate that not all of the outer membrane
      proteins elicited antibody responses when they work together in the form of live
      or inactivated bacteria; live vaccine elicits more protective antibodies, which
      contribute to higher immune protection in live vaccine than inactivated vaccine.
      Notably, the recombinant proteins might be different from those separated from
      live bacteria, and they might be different in their immunogenic potencies.

PMID- 30095908
TI  - Bioactive Resorcylic Acid Lactones with Different Ring Systems from Desert Plant
      Endophytic Fungus Chaetosphaeronema hispidulur.
AB  - Five new resorcylic acid lactones (RALs) hispidulactones A-E (1, 4, 5, 8, and 9),
      a new natural product (2), and four known ones (3, 6, 7, and 10) with different
      ring systems were isolated from the desert plant endophytic fungus
      Chaetosphaeronema hispidulur. The new compounds were characterized by NMR data,
      CD spectra, and X-ray experiment. The new natural product (2) displayed strongly
      biological effects on the seedlings growth of Arabidopsis thaliana, Digitaria
      sanguinalis, and Echinochloa crusgalli with a dose-dependent relationship.
      Compounds 1, 2, and 6 were also tested cytotoxic activities against three cancer
      cell lines HCT116, Hela, and MCF7 and only did the new natural product (2)
      display biological activities with IC50 values at 54.86 +/- 1.52, 4. 90 +/- 0.02,
      and 20.04 +/- 4.00 MUM, respectively, whereas the IC50 values of the positive
      control cis-platinum were 11.36 +/- 0.42, 3.54 +/- 0.12, and 14.32 +/- 1.01 MUM,
      respectively.

PMID- 30095910
TI  - Rational Design and Structure Validation of a Novel Peptide Inhibitor of the
      Adenomatous-Polyposis-Coli (APC)-Rho-Guanine-Nucleotide-Exchange-Factor-4 (Asef)
      Interaction.
AB  - In colorectal cancer, adenomatous polyposis coli (APC) interacts with Rho guanine
      nucleotide-exchange factor 4 (Asef), thereby stimulating aberrant colorectal
      cancer-cell migration. Consequently, the APC-Asef interaction represents a
      promising therapeutic target for mitigating colorectal-cancer migration. In this
      study, we adopted the rational-design strategy involving the introduction of
      intramolecular hydrogen bonds and optimization of the lipophilic substituents to
      improve the binding affinities of peptides, leading to the discovery of MAI-400,
      the best inhibitor of the APC-Asef interaction known to date ( Kd = 0.012 MUM,
      IC50 = 0.25 MUM). Comprehensive evaluation of MAI-400 by biochemical and
      biophysical assays revealed the formation and effect of an intramolecular
      hydrogen bond. A cell-based assay showed MAI-400 efficiently blocking the APC
      Asef interaction in a dose-dependent manner. Therefore, our study provides a best
      in-class inhibitor, MAI-400, based on the rational drug design and structural
      validation, that can effectively inhibit the APC-Asef interaction.

PMID- 30095911
TI  - Ultrafast Transient Absorption Spectroscopy of UO22+ and [UO2Cl].
AB  - For the only water coordinated "free" uranyl(VI) aquo ion in perchlorate solution
      we identified and assigned several different excited states and showed that the
      3Delta state is the luminescent triplet state from transient absorption
      spectroscopy. With additional data from other spectroscopic methods (TRLFS,
      UV/vis) we generated a detailed Jablonski diagram and determined rate constants
      for several state transitions, like the inner conversion rate constant from the
      3Phi state to the 3Delta state transition to be 0.35 ps-1. In contrast to
      luminescence measurements, it was possible to observe the highly quenched
      uranyl(VI) ion in highly concentrated chloride solution by TAS and we were able
      to propose a dynamic quenching mechanism, where chloride complexation is followed
      by the charge transfer from the excited state uranyl(VI) to chloride. This
      proposed quenching route is supported by TD-DFT calculations.

PMID- 30095912
TI  - One-Pot Unsymmetrical {[4 + 2] and [4 + 2]} Double Annulations of o/ o'-C-H Bonds
      of Arenes: Access to Unusual Pyranoisoquinolines.
AB  - With the aid of a transformable sulfoximine directing group, unprecedented one
      pot unsymmetrical double annulations {[4 + 2] and [4 + 2]} of hetero(arenes) with
      alkynes are revealed under Ru(II) catalysis. Functionalization of both ortho-C-H
      bonds of (hetero)arene is reflected in the building of unusual 6,6-fused
      pyranoisoquinoline skeletons. Construction of four [(C-C)-(C-N) and (C-C)-(C-O)]
      bonds occurs in one step under single catalytic conditions. The challenging
      unsymmetrical double annulations of both o-C-H bonds of arenes with two distinct
      alkynes is effectively demonstrated. Control experiments and deuterium scrambling
      findings are shown.

PMID- 30095913
TI  - Rovibrational Considerations for the Monomers and Dimers of Magnesium Hydride and
      Magnesium Fluoride.
AB  - Magnesium is an understudied chemical element that is quite useful in materials
      science and may be an essential astrochemical building block for grain formation
      in proto-planetary disks. This work provides quantum chemical prediction for the
      vibrational and rovibrational spectra of the structurally similar magnesium
      hydride and magnesium fluoride monomers and dimers. Magnesium fluoride is
      commonly utilized in infrared-observing windows and is a known terrestrial
      mineral, sellaite. Magnesium hydride is likely to exist in various astrophysical
      environments. Comparison of the anharmonic quantum chemical spectral data
      computed in this work to known gas phase values for MgH2 is excellent with the
      computed 1584.1 cm-1 antisymmetric Mg-H stretch less than 5 cm-1 below experiment
      for example. The condensed phase vibrational attributions of the dimer, however,
      are less comparable with the present results potentially indicating that some of
      the previous assignments may need to be revisited. The magnesium fluoride monomer
      and dimer have no previous vibrational experimental results reported, and the
      work here should be solid predictions as to their spectral features for
      comparison either to laboratory work or potentially even to interstellar
      observations.

PMID- 30095914
TI  - Optical and Chemical Characterization of Uranium Dioxide (UO2) and Uraninite
      Mineral: Calculation of the Fundamental Optical Constants.
AB  - Uranium dioxide (UO2) is a material with historical and emerging applications in
      numerous areas such as photonics, nuclear energy, and aerospace electronics.
      While often grown synthetically as single-crystal UO2, the mineralogical form of
      UO2 called uraninite is of interest as a precursor to various chemical processes
      involving uranium-bearing chemicals. Here, we investigate the optical and
      chemical properties of a series of three UO2 specimens: synthetic single-crystal
      UO2, uraninite ore of relatively high purity, and massive uraninite mineral
      containing numerous impurities. An optical technique called single-angle
      reflectance spectroscopy was used to derive the optical constants n and k of
      these uranium specimens by measuring the specular reflectance spectra of a
      polished surface across the mid- and far-infrared spectral domains (ca. 7000-50
      cm-1). X-ray diffractometry, scanning electron microscopy, and energy-dispersive
      X-ray spectroscopy were further used to analyze the surface composition of the
      mineralogical forms of UO2. Most notably, the massive uraninite mineral was
      observed to contain significant deposits of calcite and quartz in addition to UO2
      (as well as other metal oxides and radioactive decay products). Knowledge of the
      infrared optical constants for this series of uranium chemicals facilitates
      nondestructive, noncontact detection of UO2 under a variety of conditions.

PMID- 30095915
TI  - Efficacy of Apigenin and Miltefosine Combination Therapy against Experimental
      Cutaneous Leishmaniasis.
AB  - Leishmaniasis is a neglected tropical disease caused by several different species
      of Leishmania. Treatment of leishmaniasis involves a limited drug arsenal that is
      associated with severe side effects, high costs, and drug resistance. Therefore,
      combination therapy has emerged as a strategy to improve leishmaniasis treatment.
      Here, we report the interaction of miltefosine and apigenin in vitro and in vivo.
      Combination therapy using low doses of these two drugs results in good clinical
      and parasitological responses.

PMID- 30095916
TI  - NMR-Based Serum Metabolomics of Patients with Takayasu Arteritis: Relationship
      with Disease Activity.
AB  - Takayasu arteritis (TA) is a large vessel vasculitis of unknown pathogenesis.
      Assessment of disease activity is a challenge, and there is an unmet need for
      relevant biomarker(s). In our previous study, NMR based serum metabolomics had
      revealed distinctive metabolic signatures in TA patients compared with age/sex
      matched healthy controls and systemic lupus erythematosus (SLE). In this study we
      investigate whether the metabolites correlate with disease activity. Patients
      with TA fulfilling American College of Rheumatology (ACR) criteria were enrolled,
      and disease activity was assessed using Indian Takayasu Clinical Activity Score
      using acute phase reactant-erythrocyte sedimentation rate [ITAS-A (ESR)]. Sera
      were analyzed using 800 MHz NMR spectrometer to identify metabolites [based on
      partial least squares discriminant analysis (PLS-DA) VIP (variable importance in
      projection) score > 1.0 and permutation test, p-value <0.01]. 45 active and 53
      inactive TA patients with median age 27 [(IQR) 22-35 years] and 27 [(IQR) 23-37
      years], female to male ratio 3.5:1 and 4.9:1, and median duration of illness 5
      [(IQR) 2-9 years] and 3 [(IQR) 1-6 years], respectively, were enrolled. The key
      metabolites with highest discriminatory potential in active TA (ITAS-A >= 4) were
      glutamate and N-acetyl glycoprotein (NAG), both elevated, with area under the
      curve 0.775 and 0.769 ( p-value <0.001). On follow up assessment, metabolic
      spectra started to differ with change in disease activity. This large cohort of
      patients revealed metabolic profiles discriminating between clinically active and
      inactive TA patients. It suggests glutamate and NAG have strong potential as
      biomarkers for disease activity in TA and may serve as a guide to therapy. We are
      now working to further validate these results in longitudinal studies.

PMID- 30095917
TI  - Wettability Alteration of Calcite by Nonionic Surfactants.
AB  - The process of selecting an effective surfactant for wettability alteration is
      dependent on a number of factors, including mineral type, temperature, salinity,
      and nature of adsorbed oil and ultimately how the molecular structure of the
      surfactant interacts with all of these. Here, we present an experimental study of
      the effectiveness of nonionic surfactants with different hydrophobic groups and
      different lengths of hydrophilic ethylene oxide oligomers. The surfactants
      selected alter the wettability of the rock primarily by acting on the water-rock
      and oil-rock interfaces. The dynamics of wettability alteration is measured by
      the evolution of contact angles of oil drops on initially oil-wet surfaces at
      three different temperatures. Wettability alteration is found to be enhanced by
      surfactants with shorter hydrophilic units and increased temperatures.
      Experimental observations are efficiently summarized by a few thermodynamic and
      kinetic parameters. Qualitative experiments are performed to study surfactant
      induced dewetting of oil films. Finally, a model involving "coating" and
      "sweeping" mechanisms is proposed to explain the mechanism of surfactant action.

PMID- 30095919
TI  - Atomic Layer Etching: Rethinking the Art of Etch.
AB  - Atomic layer etching (ALE) is the most advanced etching technique in production
      today. In this Perspective, we describe ALE in comparison to long-standing
      conventional etching techniques, relating it to the underlying principles behind
      the ancient art of etching. Once considered too slow, we show how leveraging
      plasma has made ALE a thousand times faster than earlier approaches. While Si is
      the case study ALE material, prospects are better for strongly bound materials
      such as C, Ta, W, and Ru. Among the ALE advantages discussed, we introduce an ALE
      benefit with potentially broad application-the ALE smoothing effect-in which the
      surface flattens. Finally, regarding its well-established counterpart of atomic
      layer deposition (ALD), we discuss the combination of ALE and ALD in tackling
      real world challenges at sub-10 nm technology nodes.

PMID- 30095918
TI  - Reversible Charge-Carrier Trapping Slows Forster Energy Transfer in CdSe/CdS
      Quantum-Dot Solids.
AB  - The dynamics of photoluminescence (PL) from nanocrystal quantum dots (QDs) is
      significantly affected by the reversible trapping of photoexcited charge
      carriers. This process occurs after up to 50% of the absorption events, depending
      on the type of QD considered, and can extend the time between the photoexcitation
      and relaxation of the QD by orders of magnitude. Although many optoelectronic
      applications require QDs assembled into a QD solid, until now, reversible
      trapping has been studied only in (ensembles of) spatially separated QDs. Here,
      we study the influence of reversible trapping on the excited-state dynamics of
      CdSe/CdS core/shell QDs when they are assembled into close-packed
      "supraparticles". Time- and spectrally resolved photoluminescence (PL)
      measurements reveal competition among spontaneous emission, reversible charge
      carrier trapping, and Forster resonance energy transfer between the QDs. While
      Forster transfer causes the PL to red-shift over the first 20-50 ns after
      excitation, reversible trapping stops and even reverses this trend at later
      times. We can model this behavior with a simple kinetic Monte Carlo simulation by
      considering that charge-carrier trapping leaves the QDs in a state with zero
      oscillator strength in which no energy transfer can occur. Our results highlight
      that reversible trapping significantly affects the energy and charge-carrier
      dynamics for applications in which QDs are assembled into a QD solid.

PMID- 30095920
TI  - Effect of Cell Inner Pressure on Deposition Volume in Microinjection.
AB  - Microinjection is a widely used technique for introducing exogenous materials
      into cells. Many applications of microinjection, such as gene editing and drug
      testing, rely on the accurate control of the deposition volume. However, the
      deposition volume in microinjection is presently calibrated in an open medium
      without considering the cell inner pressure effect, which we experimentally show
      in this paper that it can induce an error as large as 30% between the actual
      deposition volume and the set volume. In this work, the relationship between the
      cell inner pressure and the deposition volume was analytically modeled and
      experimentally validated. On the basis of the developed model, the cell inner
      pressure of a given cell type can be well estimated from the injection pressure
      and the resulting deposition volume. The quantitated cell inner pressure is then
      used to reduce the error between the set volume and the actual deposition volume.
      Experiments conducted on human bladder cancer cells (T24 and RT4) showed that T24
      cells have a higher inner pressure than RT4 cells (405 +/- 45 Pa vs 341 +/- 34
      Pa), and after compensating for the cell inner pressure, the error between the
      intended set volume and the actual deposition volume into a cell became less than
      3%.

PMID- 30095921
TI  - Interaction of Proteins with Polyelectrolytes: Comparison of Theory to
      Experiment.
AB  - We discuss recent investigations of the interaction of polyelectrolytes with
      proteins. In particular, we review our recent studies on the interaction of
      simple proteins such as human serum albumin (HSA) and lysozyme with linear
      polyelectrolytes, charged dendrimers, charged networks, and polyelectrolyte
      brushes. In all cases discussed here, we combined experimental work with
      molecular dynamics (MD) simulations and mean-field theories. In particular,
      isothermal titration calorimetry (ITC) has been employed to obtain the respective
      binding constants Kb and the Gibbs free energy of binding. MD simulations with
      explicit counterions but implicit water demonstrate that counterion release is
      the main driving force for the binding of proteins to strongly charged
      polyelectrolytes: patches of positive charges located on the surface of the
      protein become multivalent counterions of the polyelectrolyte, thereby releasing
      a number of counterions condensed on the polyelectrolyte. The binding Gibbs free
      energy due to counterion release is predicted to scale with the logarithm of the
      salt concentration in the system, which is verified by both simulations and
      experiment. In several cases, namely, for the interaction of proteins with linear
      polyelectrolytes and highly charged hydrophilic dendrimers, the binding constant
      could be calculated from simulations to very good approximation. This finding
      demonstrated that in these cases explicit hydration effects do not contribute to
      the Gibbs free energy of binding. The Gibbs free energy can also be used to
      predict the kinetics of protein uptake by microgels for a given system by
      applying dynamic density functional theory. The entire discussion demonstrates
      that the direct comparison of theory with experiments can lead to a full
      understanding of the interaction of proteins with charged polymers. Possible
      implications for applications, such as drug design, are discussed.

PMID- 30095923
TI  - SIRT3 Overexpression Inhibits Growth of Kidney Tumor Cells and Enhances
      Mitochondrial Biogenesis.
AB  - SIRT3 is a NAD+-dependent mitochondrial protein deacetylase implicated in the
      regulation of central metabolism and mitochondrial proteostasis. SIRT3 is
      downregulated in clear cell renal cell carcinoma (ccRCC), which is the most
      common form of renal cancer. Although ccRCC is characterized by a typical Warburg
      like phenotype, mitochondrial dysfunction and elevated fat deposition, it is
      unknown whether SIRT3 plays a role in tumorigenesis and the development of this
      disease. In the present study, we found that SIRT3 overexpression and knockdown
      had opposing effects on the growth of ccRCC cells, decreasing and increasing the
      rate of cell proliferation, respectively. SIRT3 overexpression also increased
      mitochondrial mass in ccRCC cells. Unexpectedly, SIRT3 overexpression increased
      ROS levels, and sensitized cells to oxidative stress. Metabolomics and
      quantitative proteomics showed that SIRT3 overexpression alterd cellular
      metabolism and reversed the Warburg effect in ccRCC cells. Further studies
      demonstrated that SIRT3 promoted mitochondrial biogenesis by increasing both the
      expression and deacetylation of TFAM (transcription factor A, mitochondrial).
      Mutagenesis experiments revealed that acetylation of TFAM at K154 impaired TFAM
      interaction with mitochondrial DNA, thereby decreasing the activity of the
      protein and, consequently, mitochondrial biogenesis. Overall, our results suggest
      that SIRT3 regulates mitochondrial biogenesis and that its downregulation
      promotes a Warburg phenotype in ccRCC.

PMID- 30095922
TI  - Enhanced Triplet Sensitizing Ability of an Iridium Complex by Intramolecular
      Energy-Transfer Mechanism.
AB  - The photodynamic properties involving both intra- and intermolecular triplet
      energy transfers (ET) of a bichromophoric photosensitizer having a tris
      cyclometalated Ir(III) tethered with a pyrene derivative are studied. Due to the
      triplet energy gap of the two chromophores, a reversible intramolecular triplet
      ET equilibrium is quickly established upon photoexcitation, with the triplet
      exciton mainly residing on the acceptor side in the photostationary state. By
      virtue of the very small decay rate of triplet pyrene, a considerably extended
      triplet lifetime (2 ms) is observed. Next, the intermolecular triplet-triplet ET
      properties are investigated. Using steady-state and time-resolved spectroscopy,
      the ET rate constants from the Ir complex and pyrene unit in the sensitizer to an
      external triplet acceptor (unattached, free pyrene derivative) in solution are
      found to be around 109 s-1 and 108 M -1 s-1, respectively. In spite of a lower ET
      rate constant, the tethered pyrene serves as the main intermolecular ET channel
      because of the large, favorable intramolecular ET equilibrium ( K ~ 103).
      Importantly, this cascade ET process, from Ir complex to linked pyrene, and then
      to free pyrene, offers an overall improved ET efficiency than a direct ET from Ir
      complex to free pyrene, by virtue of the much smaller spontaneous decay rate
      compared to that of the metal complex. Finally, the more efficient ET ability is
      demonstrated experimentally by applying the molecule as sensitizer in a triplet
      triplet annihilation upconversion. The bichromophoric sensitizer achieved
      upconverted emission intensity 5 times higher than a monochromophoric Ir-complex
      analogue.

PMID- 30095924
TI  - Catalytic Reaction Mechanism for Drug Metabolism in Human Carboxylesterase-1:
      Cocaine Hydrolysis Pathway.
AB  - Carboxylesterase-1 (CE-1) is a crucial enzyme responsible for
      metabolism/activation/inactivation of xenobiotics (therapeutic agents, prodrugs,
      abused drugs, and organophosphorus nerve agents etc.) and also involved in many
      other biological processes. In this study, we performed extensive computational
      modeling and simulations to understand the fundamental reaction mechanism of
      cocaine hydrolysis catalyzed by CE-1, revealing that CE-1-catalyzed cocaine
      hydrolysis follows a novel reaction pathway with only two reaction steps: a
      single-step acylation process and a single-step deacylation process. In the
      transition states of both single-step processes, the cocaine NH group joins the
      oxyanion hole to form an additional hydrogen bond with the negatively charged
      carbonyl oxygen atom of the cocaine. Thus, the transition states are stabilized
      by both intermolecular and intramolecular hydrogen bonds with the methyl ester of
      cocaine, specifically the carbonyl oxygen atom. The rate-limiting transition
      state is associated with the acylation process, and the activation free energy
      barrier was predicted to be 20.1 kcal/mol. Further, in vitro experimental kinetic
      analysis was performed for human CE-1-catalyzed cocaine hydrolysis. For CE-1
      catalyzed cocaine hydrolysis, the computationally predicted free energy barrier
      (20.1 kcal/mol) is reasonably close to the experimentally derived turnover number
      ( kcat = 0.058 min-1), indicating the reasonability of the computational results.
      The obtained novel mechanistic insights are expected to benefit not only CE-1
      related rational drug discovery but also future research on the catalytic
      mechanism of other esterases.

PMID- 30095926
TI  - Asymmetric Free-Space Light Transport at Nonlinear Metasurfaces.
AB  - Asymmetric light transport has significantly contributed to fundamental science
      and revolutionized advanced technology in various aspects such as unidirectional
      photonic devices, optical diodes, and isolators. While metasurfaces mold wave
      fronts at will with an ultrathin flat optical element, asymmetric transport of
      light cannot be fundamentally achieved by any linear system including linear
      metasurfaces. We report asymmetric transport of free-space light at nonlinear
      metasurfaces upon transmission and reflection. Moreover, we theoretically derive
      the nonlinear generalized Snell's laws that were experimentally confirmed by the
      anomalous nonlinear refraction and reflection. The asymmetric transport at
      optically thin nonlinear interfaces is revealed by the concept of a reversed
      propagation path. Such an asymmetric transport at metasurfaces opens a new
      paradigm for free-space ultrathin lightweight optical devices with one-way
      operation including unrivaled optical valves and diodes.

PMID- 30095925
TI  - Observation of the Unconventional Photon Blockade.
AB  - We observe the unconventional photon blockade effect in quantum dot cavity QED,
      which, in contrast to the conventional photon blockade, operates in the weak
      coupling regime. A single quantum dot transition is simultaneously coupled to two
      orthogonally polarized optical cavity modes, and by careful tuning of the input
      and output state of polarization, the unconventional photon blockade effect is
      observed. We find a minimum second-order correlation g^{(2)}(0)~0.37, which
      corresponds to g^{(2)}(0)~0.005 when corrected for detector jitter, and observe
      the expected polarization dependency and photon bunching and antibunching; close
      by in parameter space, which indicates the abrupt change from phase to amplitude
      squeezing.

PMID- 30095927
TI  - Photon-Number-Resolved Measurement of an Exciton-Polariton Condensate.
AB  - We measure the full photon-number distribution emitted from a Bose condensate of
      microcavity exciton polaritons confined in a micropillar cavity. The statistics
      are acquired by means of a photon-number-resolving transition edge sensor. We
      directly observe that the photon-number distribution evolves with the nonresonant
      optical excitation power from geometric to quasi-Poissonian statistics, which is
      canonical for a transition from a thermal to a coherent state. Moreover, the
      photon-number distribution allows one to evaluate the higher-order photon
      correlations, shedding further light on the coherence formation and phase
      transition of the polariton condensate. The experimental data are analyzed in
      terms of thermal-coherent states, which gives direct access to the thermal and
      coherent fraction from the measured distributions. These results pave the way for
      a full understanding of the contribution of interactions in light-matter
      condensates in the coherence buildup at threshold.

PMID- 30095929
TI  - Demonstration of Model-Independent Control of the Longitudinal Phase Space of
      Electron Beams in the Linac-Coherent Light Source with Femtosecond Resolution.
AB  - The dynamics of intense electron bunches in free electron lasers and plasma
      wakefield accelerators are dominated by complex collective effects such as
      wakefields, space charge, coherent synchrotron radiation, and drift unpredictably
      with time, making it difficult to control and tune beam properties using model
      based approaches. We report on a first of its kind combination of automatic,
      model-independent feedback with a neural network for control of the longitudinal
      phase space of relativistic electron beams with femtosecond resolution based only
      on transverse deflecting cavity measurements.

PMID- 30095930
TI  - Generalized Gelation Theory Describes Onset of Online Extremist Support.
AB  - We introduce a generalized form of gelation theory that incorporates individual
      heterogeneity and show that it can explain the asynchronous, sudden appearance
      and growth of online extremist groups supporting ISIS (so-called Islamic State)
      that emerged globally post-2014. The theory predicts how heterogeneity impacts
      their onset times and growth profiles and suggests that online extremist groups
      present a broad distribution of heterogeneity-dependent aggregation mechanisms
      centered around homophily. The good agreement between the theory and empirical
      data suggests that existing strategies aiming to defeat online extremism under
      the assumption that it is driven by a few "bad apples" are misguided. More
      generally, this generalized theory should apply to a range of real-world systems
      featuring aggregation among heterogeneous objects.

PMID- 30095931
TI  - Verification of a Many-Ion Simulator of the Dicke Model Through Slow Quenches
      across a Phase Transition.
AB  - We use a self-assembled two-dimensional Coulomb crystal of ~70 ions in the
      presence of an external transverse field to engineer a simulator of the Dicke
      Hamiltonian, an iconic model in quantum optics which features a quantum phase
      transition between a superradiant (ferromagnetic) and a normal (paramagnetic)
      phase. We experimentally implement slow quenches across the quantum critical
      point and benchmark the dynamics and the performance of the simulator through
      extensive theory-experiment comparisons which show excellent agreement. The
      implementation of the Dicke model in fully controllable trapped ion arrays can
      open a path for the generation of highly entangled states useful for enhanced
      metrology and the observation of scrambling and quantum chaos in a many-body
      system.

PMID- 30095932
TI  - Relativistic Quantum Dynamics of Twisted Electron Beams in Arbitrary Electric and
      Magnetic Fields.
AB  - Relativistic quantum dynamics of twisted (vortex) Dirac particles in arbitrary
      electric and magnetic fields are constructed for the first time. This allows us
      to change the controversial contemporary situation when the nonrelativistic
      approximation is used for relativistic twisted electrons. The relativistic
      Hamiltonian and equations of motion in the Foldy-Wouthuysen representation are
      derived. A critical experiment for a verification of the results obtained is
      proposed. The new important effect of a radiative orbital polarization of a
      twisted electron beam in a magnetic field resulting in a nonzero average
      projection of the intrinsic orbital angular momentum on the field direction is
      predicted.

PMID- 30095933
TI  - Quantum Criticality at the Superconductor-Insulator Transition Probed by the
      Nernst Effect.
AB  - The superconductor-insulator transition (SIT) is an excellent example of a
      quantum phase transition at zero temperature, dominated by quantum fluctuations.
      These are expected to be very prominent close to the quantum critical point. So
      far, most of the experimental studies of the SIT have concentrated on transport
      properties and tunneling experiments that provide indirect information on
      criticality close to the transition. Here we present an experiment uniquely
      designed to study the evolution of quantum fluctuations through the quantum
      critical point. We utilize the Nernst effect, which has been shown to be
      effective in probing superconducting fluctuation. We measure the Nernst
      coefficient in amorphous indium oxide films tuned through the SIT and find a
      large signal on both the superconducting and the insulating sides, which peaks
      close to the critical point. The transverse Peltier coefficient alpha_{xy}, which
      is the thermodynamic quantity extracted from these measurements, follows quantum
      critical scaling with critical exponents nu~0.7 and z~1. These exponents are
      consistent with a clean X-Y model in 2+1 dimensions.

PMID- 30095934
TI  - Spinon Fermi Surface in a Cluster Mott Insulator Model on a Triangular Lattice
      and Possible Application to 1T-TaS_{2}.
AB  - 1T-TaS_{2} is a cluster Mott insulator on the triangular lattice with 13 Ta atoms
      forming a star of David cluster as the unit cell. We derive a two-dimensional XXZ
      spin-1/2 model with a four-spin ring exchange term to describe the effective low
      energy physics of a monolayer 1T-TaS_{2}, where the effective spin-1/2 degrees of
      freedom arises from the Kramers degenerate spin-orbital states on each star of
      David. A large scale density matrix renormalization group simulation is further
      performed on this effective model and we find a gapless spin liquid phase with a
      spinon Fermi surface at a moderate to large strength region of the four-spin ring
      exchange term. All peaks in the static spin structure factor are found to be
      located on the "2k_{F}" surface of a half-filled spinon on the triangular
      lattice. Experiments to detect the spinon Fermi surface phase in 1T-TaS_{2} are
      discussed.

PMID- 30095935
TI  - Distributed Quantum Metrology with Linear Networks and Separable Inputs.
AB  - We derive a bound on the ability of a linear-optical network to estimate a linear
      combination of independent phase shifts by using an arbitrary nonclassical but
      unentangled input state, thereby elucidating the quantum resources required to
      obtain the Heisenberg limit with a multiport interferometer. Our bound reveals
      that while linear networks can generate highly entangled states, they cannot
      effectively combine quantum resources that are well distributed across multiple
      modes for the purposes of metrology: In this sense, linear networks endowed with
      well-distributed quantum resources behave classically. Conversely, our bound
      shows that linear networks can achieve the Heisenberg limit for distributed
      metrology when the input photons are concentrated in a small number of input
      modes, and we present an explicit scheme for doing so.

PMID- 30095936
TI  - Phonon Lasing from Optical Frequency Comb Illumination of Trapped Ions.
AB  - We demonstrate the use of a frequency-doubled optical frequency comb to load,
      cool, and crystallize trapped atomic ions as an alternative to ultraviolet (UV)
      or even deep UV continuous-wave lasers. We find that the Doppler shift from the
      atom's oscillation in the trap, driven by the blue-detuned comb teeth, introduces
      additional cooling and amplification which gives rise to steady-state phonon
      lasing of the ion's harmonic motion in the trap. The phonon laser's gain
      saturation keeps the optical frequency comb from continually adding energy
      without bound. This protection allows us to demonstrate loading and
      crystallization of hot ions directly with the comb, eliminating the need for a
      continuous-wave cooling laser, a technique that is extendable to the deep UV.

PMID- 30095937
TI  - From Bouncing to Floating: The Leidenfrost Effect with Hydrogel Spheres.
AB  - The Leidenfrost effect occurs when a liquid or stiff sublimable solid near a hot
      surface creates enough vapor beneath it to lift itself up and float. In contrast,
      vaporizable soft solids, e.g., hydrogels, have been shown to exhibit persistent
      bouncing-the elastic Leidenfrost effect. By carefully lowering hydrogel spheres
      towards a hot surface, we discover that they are also capable of floating. The
      bounce-to-float transition is controlled by the approach velocity and
      temperature, analogously to the "dynamic Leidenfrost effect." For the floating
      regime, we measure power-law scalings for the gap geometry, which we explain with
      a model that couples the vaporization rate to the spherical shape. Our results
      reveal that hydrogels are a promising pathway for controlling floating
      Leidenfrost objects through shape.

PMID- 30095938
TI  - Path Integral Approach to Quantum Thermodynamics.
AB  - Work belongs to the most basic notions in thermodynamics but it is not well
      understood in quantum systems, especially in open quantum systems. By introducing
      a novel concept of the work functional along an individual Feynman path, we
      invent a new approach to study thermodynamics in the quantum regime. Using the
      work functional, we derive a path integral expression for the work statistics. By
      performing the h expansion, we analytically prove the quantum-classical
      correspondence of the work statistics. In addition, we obtain the quantum
      correction to the classical fluctuating work. We can also apply this approach to
      an open quantum system in the strong coupling regime described by the quantum
      Brownian motion model. This approach provides an effective way to calculate the
      work in open quantum systems by utilizing various path integral techniques. As an
      example, we calculate the work statistics for a dragged harmonic oscillator in
      both isolated and open quantum systems.

PMID- 30095928
TI  - ^{7}Be(n,p)^{7}Li Reaction and the Cosmological Lithium Problem: Measurement of
      the Cross Section in a Wide Energy Range at n_TOF at CERN.
AB  - We report on the measurement of the ^{7}Be(n,p)^{7}Li cross section from thermal
      to approximately 325 keV neutron energy, performed in the high-flux experimental
      area (EAR2) of the n_TOF facility at CERN. This reaction plays a key role in the
      lithium yield of the big bang nucleosynthesis (BBN) for standard cosmology. The
      only two previous time-of-flight measurements performed on this reaction did not
      cover the energy window of interest for BBN, and they showed a large discrepancy
      between each other. The measurement was performed with a Si telescope and a high
      purity sample produced by implantation of a ^{7}Be ion beam at the ISOLDE
      facility at CERN. While a significantly higher cross section is found at low
      energy, relative to current evaluations, in the region of BBN interest, the
      present results are consistent with the values inferred from the time-reversal
      ^{7}Li(p,n)^{7}Be reaction, thus yielding only a relatively minor improvement on
      the so-called cosmological lithium problem. The relevance of these results on the
      near-threshold neutron production in the p+^{7}Li reaction is also discussed.

PMID- 30095939
TI  - Demonstration of an Effective Ultrastrong Coupling between Two Oscillators.
AB  - When the coupling rate between two quantum systems becomes as large as their
      characteristic frequencies, it induces dramatic effects on their dynamics and
      even on the nature of their ground state. The case of a qubit coupled to a
      harmonic oscillator in this ultrastrong coupling regime has been investigated
      theoretically and experimentally. Here, we explore the case of two harmonic
      oscillators in the ultrastrong coupling regime. Probing the properties of their
      ground state remains out of reach in natural implementations. Therefore, we have
      realized an analog quantum simulation of this coupled system by dual frequency
      pumping a nonlinear superconducting circuit. The pump amplitudes directly tune
      the effective coupling rate. We observe spectroscopic signature of a mode
      hybridization that is characteristic of the ultrastrong coupling. We
      experimentally demonstrate a key property of the ground state of this simulated
      ultrastrong coupling between modes by observing simultaneous single- and two-mode
      squeezing of the radiated field below vacuum fluctuations.

PMID- 30095941
TI  - Conditional Decoupling of Quantum Information.
AB  - Insights from quantum information theory show that correlation measures based on
      quantum entropy are fundamental tools that reveal the entanglement structure of
      multipartite states. In that spirit, Groisman, Popescu, and Winter [Phys. Rev. A
      72, 032317 (2005)PLRAAN1050-294710.1103/PhysRevA.72.032317] showed that the
      quantum mutual information I(A;B) quantifies the minimal rate of noise needed to
      erase the correlations in a bipartite state of quantum systems AB. Here, we
      investigate correlations in tripartite systems ABE. In particular, we are
      interested in the minimal rate of noise needed to apply to the systems AE in
      order to erase the correlations between A and B given the information in system
      E, in such a way that there is only negligible disturbance on the marginal BE. We
      present two such models of conditional decoupling, called deconstruction and
      conditional erasure cost of tripartite states ABE. Our main result is that both
      are equal to the conditional quantum mutual information I(A;B|E)-establishing it
      as an operational measure for tripartite quantum correlations.

PMID- 30095942
TI  - Detaching Microparticles from a Liquid Surface.
AB  - The work required to detach microparticles from fluid interfaces depends on the
      shape of the liquid meniscus. However, measuring the capillary force on a single
      microparticle and simultaneously imaging the shape of the liquid meniscus has not
      yet been accomplished. To correlate force and shape, we combined a laser scanning
      confocal microscope with a colloidal probe setup. While moving a hydrophobic
      microsphere (radius 5-10  MUm) in and out of a 2-5  MUm thick glycerol film, we
      simultaneously measured the force and imaged the shape of the liquid meniscus. In
      this way we verified the fundamental equations [D. F. James, J. Fluid Mech. 63,
      657 (1974)JFLSA70022-112010.1017/S0022112074002126; A. D. Scheludko, A. D.
      Nikolov, Colloid Polymer Sci. 253, 396 (1975)] that describe the adhesion of
      particles in flotation, deinking of paper, the stability of Pickering emulsions
      and particle-stabilized foams. Comparing experimental results with theory showed,
      however, that the receding contact angle has to be applied, which can be much
      lower than the static contact angle obtained right after jump in of the particle.

PMID- 30095943
TI  - Novel Way to Search for Light Dark Matter in Lepton Beam-Dump Experiments.
AB  - A novel mechanism to produce and detect light dark matter in experiments making
      use of GeV electrons (and positrons) impinging on a thick target (beam dump) is
      proposed. The positron-rich environment produced by the electromagnetic shower
      allows us to produce an A^{'} via nonresonant (e^{+}+e^{-}->gamma+A^{'}) and
      resonant (e^{+}+e^{-}->A^{'}) annihilation on atomic electrons. The latter
      mechanism, for some selected kinematics, results in a larger sensitivity with
      respect to limits derived by the commonly used A^{'}-strahlung. This idea,
      applied to beam-dump experiments and active beam-dump experiments, pushes down
      the current limits by an order of magnitude.

PMID- 30095940
TI  - Experimental Evidence of a Variant Neutron Spectrum from the T(t,2n)alpha
      Reaction at Center-of-Mass Energies in the Range of 16-50 keV.
AB  - Full calculations of six-nucleon reactions with a three-body final state have
      been elusive and a long-standing issue. We present neutron spectra from the
      T(t,2n)alpha (TT) reaction measured in inertial confinement fusion experiments at
      the OMEGA laser facility at ion temperatures from 4 to 18 keV, corresponding to
      center-of-mass energies (E_{c.m.}) from 16 to 50 keV. A clear difference in the
      shape of the TT-neutron spectrum is observed between the two E_{c.m.}, with the
      ^{5}He ground state resonant peak at 8.6 MeV being significantly stronger at the
      higher than at the lower energy. The data provide the first conclusive evidence
      of a variant TT-neutron spectrum in this E_{c.m.} range. In contrast to earlier
      available data, this indicates a reaction mechanism that must involve resonances
      and/or higher angular momenta than L=0. This finding provides an important
      experimental constraint on theoretical efforts that explore this and
      complementary six-nucleon systems, such as the solar ^{3}He(^{3}He,2p)alpha
      reaction.

PMID- 30095944
TI  - Phonon-Polariton Mediated Thermal Radiation and Heat Transfer among Molecules and
      Macroscopic Bodies: Nonlocal Electromagnetic Response at Mesoscopic Scales.
AB  - Thermal radiative phenomena can be strongly influenced by the coupling of phonons
      and long-range electromagnetic fields at infrared frequencies. Typically employed
      macroscopic descriptions of thermal fluctuations often ignore atomistic effects
      that become relevant at nanometric scales, whereas purely microscopic treatments
      ignore long-range, geometry-dependent electromagnetic effects. We describe a
      mesoscopic framework for modeling thermal fluctuation phenomena among molecules
      near macroscopic bodies, conjoining atomistic treatments of electronic and
      vibrational fluctuations obtained from density functional theory in the former
      with continuum descriptions of electromagnetic scattering in the latter. The
      interplay of these effects becomes particularly important at mesoscopic scales,
      where phonon polaritons can be strongly influenced by the objects' finite sizes,
      shapes, and nonlocal or many-body response to electromagnetic fluctuations. We
      show that, even in small but especially in elongated low-dimensional molecules,
      such effects can modify thermal emission and heat transfer by orders of magnitude
      and produce qualitatively different behavior compared to predictions based on
      local, dipolar, or pairwise approximations.

PMID- 30095945
TI  - Parity Anomaly Cancellation in Three-Dimensional QED with a Single Massless Dirac
      Fermion.
AB  - We study three-dimensional noncompact QED with a single two-component massless
      fermion and two infinitely massive regulator fermions of half the charge using
      the lattice overlap formalism. The parity anomaly is expected to cancel exactly
      between the massless and regulator fermions in the continuum, but this
      cancellation is inexact on a lattice akin to lattice chiral gauge theories. We
      show nonperturbatively that parity-breaking terms vanish in the continuum limit
      at any finite volume. We present numerical evidence that the resulting parity
      invariant theory spontaneously breaks parity in the infinite volume limit.

PMID- 30095946
TI  - Optical Chirality in Dispersive and Lossy Media.
AB  - Several dynamical properties of electromagnetic waves such as energy, momentum,
      angular momentum, and optical helicity have been recently reexamined in
      dispersive and lossless media. Here, we address an alternative derivation for the
      optical chirality, extending it so as to include dissipative effects as well. To
      this end, we first elaborate on the most complete form of the conservation law
      for the optical chirality, without any restrictions on the nature of the medium.
      As a result we find a general expression for the optical chirality density both
      in lossless and lossy dispersive media. Our definition is perfectly consistent
      with that originally introduced for electromagnetic fields in free space, and is
      applicable to any material system, including dielectrics, plasmonic
      nanostructures, and left-handed metamaterials.

PMID- 30095947
TI  - Duality Between 3D Massive Thirring and Maxwell-Chern-Simons Models from 2D
      Bosonization.
AB  - Bosonization techniques are important nonperturbative tools in quantum field
      theory. In three dimensions they possess interesting connections to topologically
      ordered systems and ultimately have driven the observation of an impressive web
      of dualities. In this work, we use the quantum wires formalism to show how the
      fermion-boson mapping relating the low-energy regime of the massive Thirring
      model in three spacetime dimensions with the Maxwell-Chern-Simons model can be
      obtained from the exact bosonization in two dimensions.

PMID- 30095948
TI  - Quantum Slow Relaxation and Metastability due to Dynamical Constraints.
AB  - One of the general mechanisms that give rise to the slow cooperative relaxation
      characteristic of classical glasses is the presence of kinetic constraints in the
      dynamics. Here we show that dynamical constraints can similarly lead to slow
      thermalization and metastability in translationally invariant quantum many-body
      systems. We illustrate this general idea by considering two simple models: (i) a
      one-dimensional quantum analogue to classical constrained lattice gases where
      excitation hopping is constrained by the state of neighboring sites, mimicking
      excluded-volume interactions of dense fluids; and (ii) fully packed quantum
      dimers on the square lattice. Both models have a Rokhsar-Kivelson (RK) point at
      which kinetic and potential energy constants are equal. To one side of the RK
      point, where kinetic energy dominates, thermalization is fast. To the other,
      where potential energy dominates, thermalization is slow, memory of initial
      conditions persists for long times, and separation of timescales leads to
      pronounced metastability before eventual thermalization. Furthermore, in analogy
      with what occurs in the relaxation of classical glasses, the slow-thermalization
      regime displays dynamical heterogeneity as manifested by spatially segregated
      growth of entanglement.

PMID- 30095949
TI  - Spontaneous Helical Order of a Chiral p-Wave Superfluid Confined in Nanoscale
      Channels.
AB  - Strong interactions that favor chiral p-wave pairing, combined with strong pair
      breaking by confining boundaries, are shown to lead to new equilibrium states
      with different broken symmetries. Based on a strong-coupling extension of the
      Ginzburg-Landau theory that accurately accounts for the thermodynamics and phase
      diagram of the bulk phases of superfluid ^{3}He, we predict new phases of
      superfluid ^{3}He for confined geometries that spontaneously break rotational and
      translational symmetry in combination with parity and time-reversal symmetry. One
      of the newly predicted phases exhibits a unique combination of chiral and helical
      order that is energetically stable in cylindrical channels of radius approaching
      the Cooper pair coherence length, e.g., R~100  nm. Precise numerical minimization
      of the free energy yields a broad region of stability of the helical phase as a
      function of pressure and temperature, in addition to three translationally
      invariant phases with distinct broken spin and orbital rotation symmetries. The
      helical phase is stable at both high and low pressures and favored by boundaries
      with strong pair breaking. We present calculations of transverse NMR frequency
      shifts as functions of rf pulse tipping angle, magnetic field orientation, and
      temperature as signatures of these broken symmetry phases.

PMID- 30095950
TI  - Response Functions as Quantifiers of Non-Markovianity.
AB  - Quantum non-Markovianity is crucially related to the study of dynamical maps,
      which are usually derived for initially factorized system-bath states. We
      demonstrate that linear response theory also provides a way to derive dynamical
      maps but for initially correlated (and, in general, entangled) states.
      Importantly, these maps are always time-translational invariant and allow for a
      much simpler quantification of non-Markovianity compared to previous approaches.
      We apply our theory to the Caldeira-Leggett model, for which our quantifier is
      valid beyond linear response and can be expressed analytically. We find that a
      classical Brownian particle coupled to an Ohmic bath can already exhibit non
      Markovian behavior, a phenomenon related to the initial state preparation
      procedure. Furthermore, for a peaked spectral density, we show that there is no
      monotonic relation between our quantifier and the system-bath coupling strength,
      the sharpness of the peak or the resonance frequency in the bath.

PMID- 30095951
TI  - Flexible Fiber Reveals the Two-Point Statistical Properties of Turbulence.
AB  - We study the dynamics of a flexible fiber freely moving in a three-dimensional
      fully developed turbulent field and present a phenomenological theory to describe
      the interaction between the fiber elasticity and the turbulent flow. This theory
      leads to the identification of two distinct regimes of flapping, which we
      validate against direct numerical simulations fully resolving the fiber dynamics.
      The main result of our analysis is the identification of a flapping regime where
      the fiber, despite its elasticity, is slaved to the turbulent fluctuations. In
      this regime the fiber can be used to measure two-point statistical observables of
      turbulence, including scaling exponents of velocity structure functions, the sign
      of the energy cascade and the energy flux of turbulence, as well as the
      characteristic times of the eddies within the inertial range of scales. Our
      results are expected to have a deep impact on the experimental turbulence
      research as a new way, accurate and efficient, to measure two-point, and more
      generally multipoint, statistics of turbulence.

PMID- 30095952
TI  - Quantum Generative Adversarial Learning.
AB  - Generative adversarial networks represent a powerful tool for classical machine
      learning: a generator tries to create statistics for data that mimics those of a
      true data set, while a discriminator tries to discriminate between the true and
      fake data. The learning process for generator and discriminator can be thought of
      as an adversarial game, and under reasonable assumptions, the game converges to
      the point where the generator generates the same statistics as the true data and
      the discriminator is unable to discriminate between the true and the generated
      data. This Letter introduces the notion of quantum generative adversarial
      networks, where the data consist either of quantum states or of classical data,
      and the generator and discriminator are equipped with quantum information
      processors. We show that the unique fixed point of the quantum adversarial game
      also occurs when the generator produces the same statistics as the data. Neither
      the generator nor the discriminator perform quantum tomography; linear programing
      drives them to the optimal. Since quantum systems are intrinsically
      probabilistic, the proof of the quantum case is different from-and simpler than
      the classical case. We show that, when the data consist of samples of
      measurements made on high-dimensional spaces, quantum adversarial networks may
      exhibit an exponential advantage over classical adversarial networks.

PMID- 30095953
TI  - Relating Chain Conformations to Extensional Stress in Entangled Polymer Melts.
AB  - Nonlinear extensional flows are common in polymer processing, but they remain
      challenging theoretically because dramatic stretching of chains deforms the
      entanglement network far from equilibrium. Here, we present coarse-grained
      simulations of extensional flows in entangled polymer melts for Rouse-Weissenberg
      numbers Wi_{R}=0.06-52 and Hencky strains epsilon>=6. Simulations reproduce
      experimental trends in extensional viscosity with time, rate, and molecular
      weight. Studies of molecular structure reveal an elongation and thinning of the
      confining tube with increasing Wi_{R}. The rising stress is quantitatively
      consistent with the decreasing entropy of chains at the equilibrium entanglement
      length. Molecular weight dependent trends in viscosity are related to a crossover
      from the Newtonian limit to a high rate limit that scales differently with chain
      length.

PMID- 30095955
TI  - Single-Mode Phononic Wire.
AB  - Photons and electrons transmit information to form complex systems and networks.
      Phonons on the other hand, the quanta of mechanical motion, are often considered
      only as carriers of thermal energy. Nonetheless, their flow can also be molded in
      fabricated nanoscale circuits. We design and experimentally demonstrate wires for
      phonons by patterning the surface of a silicon chip. Our device eliminates all
      but one channel of phonon conduction, allowing coherent phonon transport over
      millimeter length scales. We characterize the phononic wire optically, by
      coupling it strongly to an optomechanical transducer. The phononic wire enables
      new ways to manipulate information and energy on a chip. In particular, our
      result is an important step towards realizing on-chip phonon networks, in which
      quantum information is transmitted between nodes via phonons.

PMID- 30095954
TI  - Floquet Spectroscopy of a Strongly Driven Quantum Dot Charge Qubit with a
      Microwave Resonator.
AB  - We experimentally investigate a strongly driven GaAs double quantum dot charge
      qubit weakly coupled to a superconducting microwave resonator. The Floquet states
      emerging from strong driving are probed by tracing the qubit-resonator resonance
      condition. In this way, we probe the resonance of a qubit that is driven in an
      adiabatic, a nonadiabatic, or an intermediate rate, showing distinct quantum
      features of multiphoton processes and a fringe pattern similar to Landau-Zener
      Stuckelberg interference. Our resonant detection scheme enables the investigation
      of novel features when the drive frequency is comparable to the resonator
      frequency. Models based on the adiabatic approximation, rotating wave
      approximation, and Floquet theory explain our experimental observations.

PMID- 30095957
TI  - Efficient Adiabatic Spin-Dependent Kicks in an Atom Interferometer.
AB  - We present an atom interferometry technique in which the beam splitter is split
      into two separate operations. A microwave pulse first creates a spin-state
      superposition, before optical adiabatic passage spatially separates the arms of
      that superposition. Despite using a thermal atom sample in a small (600  MUm)
      interferometry beam, this procedure delivers an efficiency of 99% per hk of
      momentum separation. Utilizing this efficiency, we first demonstrate
      interferometry with up to 16hk momentum splitting and free-fall limited
      interrogation times. We then realize a single-source gradiometer, in which two
      interferometers measuring a relative phase originate from the same atomic wave
      function. Finally, we demonstrate a resonant interferometer with over 100
      adiabatic passages, and thus over 400hk total momentum transferred.

PMID- 30095956
TI  - Correlation of Electron Tunneling and Plasmon Propagation in a Luttinger Liquid.
AB  - Quantum-confined electrons in one dimension behave as a Luttinger liquid.
      However, unambiguous demonstration of Luttinger liquid phenomena in single-walled
      carbon nanotubes (SWNTs) has been challenging. Here we investigate well-defined
      SWNT cross junctions with a point contact between two Luttinger liquids and
      combine electrical transport and optical nanoscopy measurements to correlate
      completely different physical properties (i.e., the electron tunneling and the
      plasmon propagation) in the same Luttinger liquid system. The suppressed electron
      tunneling at SWNT junctions exhibits a power-law scaling, which yields a
      Luttinger liquid interaction parameter that agrees quantitatively with that
      independently determined from the plasmon velocity based on the near-field
      optical nanoscopy.

PMID- 30095958
TI  - Viscous Wave Breaking and Ligament Formation in Microfluidic Systems.
AB  - Rapid layering of viscous materials in microsystems encompasses a range of
      hydrodynamic instabilities that facilitate mixing and emulsification processes of
      fluids having large differences in viscosity. We experimentally study the
      stability of high-viscosity stratifications made of miscible and immiscible fluid
      pairs in square microchannels and characterize the propagation dynamics of
      interfacial waves, including breaking and viscous ligament entrainment from wave
      crests at moderate Reynolds numbers. For large viscosity contrasts, parallel
      fluid streams adopt widely different velocities and provide a simple model system
      to probe the role of inflectional instabilities of stratified microflows in
      relation with classic inviscid-stability theory. We reveal novel viscous wave
      regimes and unravel dispersion relationships in the presence and absence of
      interfacial tension. Detailed examination of wave celerity shows the existence of
      optimal operation conditions for passively disturbing miscible fluid flows and
      continuously dispersing low-and high-viscosity fluids at the small scale.

PMID- 30095959
TI  - Constraining Gluonic Quartic Gauge Coupling Operators with gg->gammagamma.
AB  - Gluon-gluon to photon-photon scattering gg->gammagamma offers to the LHC
      experiments a uniquely powerful probe of dimension-8 operators in the standard
      model effective field theory that are quadratic in both the electromagnetic and
      gluonic field-strength tensors, such as would appear in the Born-Infeld extension
      of the standard model. We use 13-TeV ATLAS data on the production of isolated
      photon pairs to set lower limits on the scales of dimension-8 operators M?1  TeV
      and discuss the prospective sensitivities of possible future hadron colliders.

PMID- 30095960
TI  - Entanglement Induced Interactions in Binary Mixtures.
AB  - We establish a conceptual framework for the identification and the
      characterization of induced interactions in binary mixtures and reveal their
      intricate relation to entanglement between the components or species of the
      mixture. Exploiting an expansion in terms of the strength of the entanglement
      among the two species enables us to deduce an effective single-species
      description. In this way, we naturally incorporate the mutual feedback of the
      species and obtain induced interactions for both species which are effectively
      present among the particles of same type. Importantly, our approach incorporates
      few-body and inhomogeneous systems extending the scope of induced interactions
      where two particles interact via a bosonic bath-type environment. Employing the
      example of a one-dimensional ultracold Bose-Fermi mixture, we obtain induced Bose
      Bose and Fermi-Fermi interactions with short-range attraction and long-range
      repulsion. With this, we show how beyond species mean-field physics visible in
      the two-body correlation functions can be understood via the induced
      interactions.

PMID- 30095961
TI  - Rotational Friction and Diffusion of Quantum Rotors.
AB  - We present the Markovian quantum master equation describing rotational
      decoherence, friction, diffusion, and thermalization of planar, linear, and
      asymmetric rotors in contact with a thermal environment. It describes how an
      arbitrary initial rotation state decoheres and evolves toward a Gibbs-like
      thermal ensemble, as we illustrate numerically for the linear and the planar top,
      and it yields the expected rotational Fokker-Planck equation of Brownian motion
      in the semiclassical limit.

PMID- 30095962
TI  - Direct Microwave Measurement of Andreev-Bound-State Dynamics in a Semiconductor
      Nanowire Josephson Junction.
AB  - The modern understanding of the Josephson effect in mesosopic devices derives
      from the physics of Andreev bound states, fermionic modes that are localized in a
      superconducting weak link. Recently, Josephson junctions constructed using
      semiconducting nanowires have led to the realization of superconducting qubits
      with gate-tunable Josephson energies. We have used a microwave circuit QED
      architecture to detect Andreev bound states in such a gate-tunable junction based
      on an aluminum-proximitized indium arsenide nanowire. We demonstrate coherent
      manipulation of these bound states, and track the bound-state fermion parity in
      real time. Individual parity-switching events due to nonequilibrium
      quasiparticles are observed with a characteristic timescale T_{parity}=160+/-10 
      MUs. The T_{parity} of a topological nanowire junction sets a lower bound on the
      bandwidth required for control of Majorana bound states.

PMID- 30095963
TI  - Kinetic Spinodal Instabilities in the Mott Transition in V_{2}O_{3}: Evidence
      from Hysteresis Scaling and Dissipative Phase Ordering.
AB  - We present the first systematic observation of scaling of thermal hysteresis with
      the temperature scanning rate around an abrupt thermodynamic transition in
      correlated electron systems. We show that the depth of supercooling and
      superheating in vanadium sesquioxide (V_{2}O_{3}) shifts with the temperature
      quench rates. The dynamic scaling exponent is close to the mean field prediction
      of 2/3. These observations, combined with the purely dissipative continuous
      ordering seen in "quench-and-hold" experiments, indicate departures from
      classical nucleation theory toward a barrier-free phase ordering associated with
      critical dynamics. Observation of critical-like features and scaling in a
      thermally induced abrupt phase transition suggests that the presence of a
      spinodal-like instability is not just an artifact of the mean field theories but
      can also exist in the transformation kinetics of real systems, surviving
      fluctuations.

PMID- 30095964
TI  - How Structural Defects Affect the Mechanical and Electrical Properties of Single
      Molecular Wires.
AB  - We report how individual defects affect single graphene nanoribbons by scanning
      tunneling and atomic force microscopy pulling experiments simultaneously
      accessing their electrical and mechanical properties. The on-surface
      polymerization of the graphene nanoribbons is controlled by cooperative effects
      as theoretically suggested. Further, we find, with the help of atomistic
      simulations, that defects substantially vary the molecule-substrate coupling and
      drastically increase the flexibility of the graphene nanoribbons while keeping
      their desirable electronic properties intact.

PMID- 30095965
TI  - Observation of the Unconventional Photon Blockade in the Microwave Domain.
AB  - We have observed the unconventional photon blockade effect for microwave photons
      using two coupled superconducting resonators. As opposed to the conventional
      blockade, only weakly nonlinear resonators are required. The blockade is revealed
      through measurements of the second order correlation function g^{(2)}(t) of the
      microwave field inside one of the two resonators. The lowest measured value of
      g^{(2)}(0) is 0.4 for a resonator population of approximately 10^{-2} photons.
      The time evolution of g^{(2)}(t) exhibits an oscillatory behavior, which is
      characteristic of the unconventional photon blockade.

PMID- 30095966
TI  - Solvent Hydrodynamics Enhances the Collective Diffusion of Membrane Lipids.
AB  - The collective motion of membrane lipids over hundreds of nanometers and
      nanoseconds plays an essential role in the formation of submicron complexes of
      lipids and proteins in the cell membrane. These dynamics are difficult to access
      experimentally and are currently poorly understood. One of the conclusions of the
      celebrated Saffman-Debruck (SD) theory is that lipid disturbances smaller than
      the Saffman length (microns) are not affected by the hydrodynamics of the
      embedding solvent. Using molecular dynamics and coarse-grained models with
      implicit hydrodynamics we show that this is not true. Hydrodynamic interactions
      between the membrane and the solvent strongly enhance the short-time collective
      diffusion of lipids at all scales. The momentum transferred between the membrane
      and the solvent in the normal direction (not considered by the SD theory)
      propagates tangentially over the membrane inducing long-ranged repulsive forces
      amongst lipids. As a consequence, the lipid collective diffusion coefficient
      increases proportionally to the disturbance wavelength. We find quantitative
      agreement with the predicted anomalous diffusion in quasi-two-dimensional
      dynamics, observed in colloids confined to a plane but embedded in a three
      dimensional solvent.

PMID- 30095967
TI  - Erratum: Chiral Effective Field Theory Predictions for Muon Capture on Deuteron
      and ^{3}He [Phys. Rev. Lett. 108, 052502 (2012)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.108.052502.

PMID- 30095968
TI  - Detecting Superconductivity in the High Pressure Hydrides and Metallic Hydrogen
      from Optical Properties.
AB  - We present a new technique for measuring the critical temperature T_{c} in the
      high pressure, high T_{c} electron-phonon-driven superconducting hydrides. This
      technique does not require connecting leads to the sample. In the region of the
      absorption spectrum above the sum of the optical gap and maximum phonon energy,
      the reflectance mirrors the temperature variation of the superconducting order
      parameter. For an appropriately chosen value of fixed photon energy, the
      temperature dependence of the reflectance varies much more rapidly below T=T_{c}
      than above. It increases with increasing temperature in the superconducting state
      while it decreases in the normal state. Examining the temperature dependence of
      the reflectance at a fixed photon energy, there is a cusp at T=T_{c} which
      provides a measurement of the critical temperature. We discuss these issues
      within the context of the recently reported atomic metallic phase of hydrogen,
      but our proposed technique should prove useful for other hydrides with large
      coupling to high energy phonons.

PMID- 30095969
TI  - Mitochondrial bioenergetics and cardiolipin alterations in myocardial
      ischemia/reperfusion injury. Implications for pharmacological cardioprotection.
AB  - Mitochondrial dysfunction plays a central role in myocardial ischemia/reperfusion
      (I/R) injury. Increased reactive oxygen species production, impaired electron
      transport chain activity, aberrant mitochondrial dynamics, calcium overload and
      opening of the mitochondrial permeability transition pore have been proposed as
      major contributory factors to mitochondrial dysfunction during myocardial I/R
      injury. Cardiolipin (CL), a mitochondria-specific phospholipid, plays a pivotal
      role in multiple mitochondrial bioenergetic processes, including respiration and
      energy conversion, in mitochondrial morphology and dynamics, as well as, in
      several steps of the apoptotic process. Changes in CL levels, species composition
      and degree of oxidation may have deleterious consequences for mitochondrial
      function with important implications in a variety of pathophysiological
      conditions, including myocardial I/R injury. In this review, we focus on the role
      played by cardiolipin alterations in mitochondrial dysfunction in myocardial I/R
      injury. Pharmacological strategies to prevent myocardial injury during I/R
      targeting mitochondrial cardiolipin are also examined.

PMID- 30095970
TI  - In Search of Clinical Factors that Predict Risk for Pneumocystis jirovecii
      Pneumonia in Patients without HIV/AIDS.

PMID- 30095971
TI  - Disparities in the Efficacy of Metformin in Combination with Dipeptidyl Peptidase
      4 Inhibitor as Initial Treatment Stratified by Dosage and Ethnicity: A Meta
      Analysis.
AB  - BACKGROUND: As initial combination therapy of metformin and dipeptidyl peptidase
      4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of
      metformin or low dose of metformin and the efficacy and safety for the
      combination use for Asian and Caucasian patients were not clear. METHODS: Double
      blind randomized controlled trials comparing the efficacy of initial combination
      therapy of metformin and DPP-4 inhibitors with metformin monotherapy were
      included. The primary outcome was a result of comparisons between high-dose
      combination therapy and low-dose combination therapy in terms of efficacy and
      safety. RESULTS: A total of 11 studies were included. The results indicated that
      the high-dose combination therapy showed significant decreases in hemoglobin A1c
      (HbA1c) (-0.32%, P < 0.05), fasting plasma glucose (FPG) (-0.63 mmol/L, P <
      0.05), and postprandial glucose (PPG) (-0.99 mmol/L, P < 0.05), but less increase
      in body weight (-0.54 kg, P < 0.05) when compared with low-dose combination
      therapy, corrected by metformin monotherapy. Moreover, the high-dose combination
      therapy exhibited significant decreases in HbA1c (-0.24%, P < 0.05), FPG (-0.54
      mmol/L, P < 0.05), and PPG (-0.94 mmol/L, P < 0.05) in the Caucasian population
      than in the Asian population, corrected by metformin monotherapy. CONCLUSION: As
      an initial treatment, the high dose of metformin in combination with DPP-4
      inhibitors not only provided better glycemic control but also had less effect on
      weight gain compared with the low-dose combination therapy through the correction
      of metformin monotherapy. Moreover, initial combination therapy in the Caucasian
      population showed better glycemic control and less increase in body weight
      compared with the Asian population.

PMID- 30095972
TI  - Stranger in a Strange Land: IL-8 in the Mouse Lung?

PMID- 30095973
TI  - Regulation of sympathetic vasomotor activity by the hypothalamic paraventricular
      nucleus in normotensive and hypertensive states.
AB  - The hypothalamic paraventricular nucleus (PVN) is a unique and important brain
      region involved in the control of cardiovascular, neuroendocrine, and other
      physiological functions pertinent to homeostasis. The PVN is a major source of
      excitatory drive to the spinal sympathetic outflow via both direct and indirect
      projections. In this review, we discuss the role of the PVN in the regulation of
      sympathetic output in normal physiological conditions and in hypertension. In
      normal healthy animals, the PVN presympathetic neurons do not appear to have a
      major role in sustaining resting sympathetic vasomotor activity or in regulating
      sympathetic responses to short-term homeostatic challenges such as acute
      hypotension or hypoxia. Their role is, however, much more significant during
      longer-term challenges, such as sustained water deprivation, chronic intermittent
      hypoxia and pregnancy. The PVN also appears to have a major role in generating
      the increased sympathetic vasomotor activity that is characteristic of multiple
      forms of hypertension. Recent studies in the spontaneously hypertensive rat (SHR)
      model show that impaired inhibitory and enhanced excitatory synaptic inputs to
      PVN presympathetic neurons are the basis for heightened sympathetic outflow in
      hypertension. We discuss the molecular mechanisms underlying the presynaptic and
      postsynaptic alterations in GABAergic and glutamatergic inputs to PVN
      presympathetic neurons in hypertension. In addition, we discuss the ability of
      exercise training to correct sympathetic hyperactivity by restoring blood-brain
      barrier integrity, reducing angiotensin II availability, and decreasing oxidative
      stress and inflammation in the PVN.

PMID- 30095974
TI  - Antibodies aggravate the development of ischemic heart failure.
AB  - Heart-specific antibodies have been widely associated with myocardial infarction
      (MI). However, it remains unclear whether autoantibodies mediate disease
      progression or are a byproduct of cardiac injury. To disambiguate the role of
      immunoglobulins in MI, we characterized the development of ischemic heart failure
      (HF) in agammaglobulinemic mice (AID-/-MUS-/-). While these animals can produce
      functional B-cells, they cannot synthesize secretory IgM (MUS-/-) or perform
      immunoglobulin class-switching (AID-/-), leading to complete antibody deficiency.
      Agammaglobulinemia did not affect overall post-MI survival but resulted in a
      significant reduction in infarct size. Echocardiographic analyses showed that
      compared to the WT infarcted controls, the AID-/-MUS-/- mice exhibited improved
      cardiac function and reduced remodeling at day 56 post-MI. These differences
      remained significant even after animals with matched infarct sizes were compared.
      Infarcted AID-/-MUS-/- mice also showed reduced myocardial expression levels of
      transcripts known to promote adverse remodeling, such as Mmp9, Col1a1, Col3a1,
      and Il6. An unbiased screening of the heart-reactivity potential in the plasma of
      WT MI animals revealed the presence of antibodies that target the myocardial scar
      and collagenase-sensitive epitopes. Moreover, we found that IgG accumulated
      within the scar tissues of infarcted mice and remained in close proximity with
      cells expressing Fcgamma receptors (CD16/32, FcgammaR), suggesting the existence
      of an in situ IgG-Fcgamma receptor axis. Collectively, our study results confirm
      that antibodies contribute to ischemic HF progression and provide novel insights
      into the mechanisms underlying this phenomenon.

PMID- 30095975
TI  - Estimation of Shoulder Behavior From the Viewpoint of Minimized Shoulder Joint
      Load Among Adolescent Baseball Pitchers.
AB  - BACKGROUND: During pitching, an overloaded joint reaction force exerted on the
      shoulder and excessive shoulder horizontal abduction at ball release are
      considered risk factors causing anterior shoulder pain for young baseball
      pitchers. Hypothesis/Purpose: The first aim was to examine the relationship
      between shoulder horizontal abduction position and force on the shoulder at ball
      release. The second was to identify the relative rotational position of the
      shoulder and the range of shoulder motion at ball release that minimize force on
      the shoulder. It was hypothesized that the amount of force on the shoulder would
      be exacerbated by excessive shoulder horizontal abduction. STUDY DESIGN:
      Descriptive laboratory study. METHODS: Participants were 183 adolescent baseball
      pitchers (mean +/- SD age, 15.5 +/- 1.2 years) without shoulder/elbow problems.
      Each pitcher threw 5 fastballs to a catcher behind a home plate. The kinematics
      and kinetics of the throwing shoulder during fastball pitching were calculated
      with 3-dimensional measurements from 36 reflective markers. In data analysis, the
      correlations were calculated between the relative rotational positions of the
      shoulder (abduction, horizontal adduction-abduction) and the forces on the
      shoulder (anterior-posterior, proximal, and superior-inferior) at ball release.
      Subsequently, the specific rotational position and range of motion of the
      shoulder at ball release that minimized forces on the shoulder were determined.
      RESULTS: Statistically significant correlations were identified between the
      magnitude of superior-inferior force on the shoulder and shoulder abduction
      position ( R2 = 0.44, P < .001) as well as between the magnitude of anterior
      posterior force on the shoulder and shoulder horizontal adduction-abduction
      position ( R2 = 0.72, P < .001). Minimal anterior-posterior and superior-inferior
      forces were obtained with a combination of 80.6 degrees  of shoulder abduction
      and 10.7 degrees  of shoulder horizontal adduction. Any deviation >5 degrees 
      from this position significantly increased the anterior-posterior and superior
      inferior forces on the shoulder. CONCLUSION: Increasing shoulder horizontal
      abduction position significantly increased the magnitude of anterior force on the
      shoulder at ball release. The combination of 80.6 degrees  of shoulder abduction
      and 10.7 degrees  of horizontal shoulder adduction minimized the shear forces on
      the shoulder at this point. CLINICAL RELEVANCE: The present data can be useful
      for screening pitching technique to prevent shoulder pain and injury with motion
      capture assessment.

PMID- 30095976
TI  - Immune Checkpoint Ligand PD-L1 Is Upregulated in Pulmonary
      Lymphangioleiomyomatosis.
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is a slow-progressing metastatic disease
      that is driven by mutations in the tumor suppressor tuberous sclerosis complex
      1/2 (TSC1/2). Rapamycin inhibits LAM cell proliferation and is the only approved
      treatment, but it cannot cause the regression of existing lesions and can only
      stabilize the disease. However, in other cancers, immunotherapies such as
      checkpoint blockade against PD-1 and its ligand PD-L1 have shown promise in
      causing tumor regression and even curing some patients. Thus, we asked whether PD
      L1 has a role in LAM progression. In vitro, PD-L1 expression in murine Tsc2-null
      cells is unaffected by mTOR inhibition with torin but can be upregulated by IFN
      gamma. Using immunohistochemistry and single-cell flow cytometry, we found
      increased PD-L1 expression both in human lung tissue from patients with LAM and
      in Tsc2-null lesions in a murine model of LAM. In this model, PD-L1 is highly
      expressed in the lung by antigen-presenting and stromal cells, and activated T
      cells expressing PD-1 infiltrate the affected lung. In vivo treatment with anti
      PD-1 antibody significantly prolongs mouse survival in the model of LAM.
      Together, these data demonstrate that PD-1/PD-L1-mediated immunosuppression may
      occur in LAM, and suggest new opportunities for therapeutic targeting that may
      provide benefits beyond those of rapamycin.

PMID- 30095977
TI  - Mechanisms of Ventilator-induced Lung Injury: Is the Elafin in the Room?

PMID- 30095979
TI  - Immune Checkpoint Inhibitor-related Pneumonitis. Incidence, Risk Factors, and
      Clinical and Radiographic Features.

PMID- 30095978
TI  - Dying Patient and Family Contributions to Nurse Distress in the ICU.
AB  - RATIONALE: Caring for patients at the end of life is emotionally taxing and may
      contribute to burnout. Nevertheless, little is known about the factors associated
      with emotional distress in intensive care unit (ICU) nurses. OBJECTIVES: To
      identify patient and family factors associated with nurses' emotional distress in
      caring for dying patients in the ICU. METHODS: One hundred nurses who cared for
      200 deceased ICU patients at two large academic medical centers in the Northeast
      United States were interviewed about patients' psychological and physical
      symptoms, their reactions to those patient experiences (e.g., emotional
      distress), and perceived factors contributing to their emotional distress.
      Logistic regression analyses modeled nurses' emotional distress as a function of
      patient symptoms and care. RESULTS: Patients' overall quality of death (odds
      ratio [OR], 3.08; 95% confidence interval [CI], 1.31-7.25), suffering (OR, 2.34;
      CI, 1.03-5.29), and loss of dignity (OR, 2.95; CI, 1.19-7.29) were significantly
      associated with nurse emotional distress. Some 40.5% (79 of 195) of nurses
      identified families' fears of patient death, and 34.4% (67 of 195) identified
      families' unrealistic expectations as contributing to their own emotional
      distress. CONCLUSIONS: Patients' emotional distress, physical distress, and
      perceived quality of death are associated with nurse emotional distress.
      Unrealistic family expectations for the patient may be a source of nurse
      emotional distress. Improving patients' quality of death, including enhancing
      their dignity, reducing their suffering, and promoting acceptance of an impending
      death among family members may improve the emotional health of nurses.

PMID- 30095980
TI  - The Effectiveness of Continuous Glucose Monitoring in Patients with Type 2
      Diabetes: A Systematic Review of Literature and Meta-analysis.
AB  - BACKGROUND: Continuous glucose monitoring (CGM) provides glucose trend
      information that can be used to guide treatment and motivate patients with
      diabetes. Currently, the evidence on effectiveness of CGM in patients with type 2
      diabetes is debatable. We aim to provide a systematic review and meta-analysis to
      synthesize current evidence of effectiveness of CGM in adults with type 2
      diabetes. MATERIALS AND METHODS: Cochrane, Embase, PubMed, and Web of Science
      were searched to include all studies that reported effectiveness of CGM in terms
      of HbA1c in adults aged 18 and older, with type 2 diabetes, on any treatment for
      diabetes. Heterogeneity (I2) was used to determine the variability between
      studies. All data were analyzed using Review Manager 5.3 software. RESULTS: Seven
      randomized controlled trials and three cohort studies, involving 1384 patients
      for real-time CGM (RT-CGM) and professional CGM (P-CGM) and 4902 patients for
      flash glucose monitoring (FGM), were included. RT-CGM and P-CGM were associated
      with a modest but statistically significant reduction in HbA1c of 0.20% (95%
      confidence interval [CI] -0.31 to -0.09) compared with control. Patients who
      received FGM had a nonsignificant reduction of 0.02% (95% CI -0.07 to 0.04)
      compared with control. The meta-analysis indicated a low heterogeneity between
      studies. CONCLUSION: Our analysis of current evidence suggests that RT-CGM and P
      CGM are effective in improving HbA1c in adults with type 2 diabetes. Due to
      insufficient evidence, it is premature to form conclusions on the effectiveness
      of FGM. Future multicenter trials accessing the effectiveness of CGM as well as
      safety and cost-effectiveness may be necessary.

PMID- 30095981
TI  - Activin Type II Receptor Blockade for Treatment of Muscle Depletion in COPD: A
      Randomized Trial.
AB  - RATIONALE: Bimagrumab is a fully human monoclonal antibody that blocks the
      activin type II receptors, preventing the activity of myostatin and other
      negative skeletal muscle regulators. OBJECTIVES: To assess the effects of
      bimagrumab on skeletal muscle mass and function in patients with COPD and reduced
      skeletal muscle mass. METHODS: Sixty-seven COPD patients (mean FEV1 1.05 L [41.6%
      predicted]; aged 40-80 years; body mass index <20 kg/m2 or appendicular skeletal
      muscle mass index <=7.25 [men] and <=5.67 [women] kg/m2), received two doses of
      either bimagrumab 30 mg/kg intravenously (n=33) or placebo (n=34) (Weeks 0 and 8)
      over 24 weeks. MEASUREMENTS AND MAIN RESULTS: We assessed changes in thigh muscle
      volume (TMV, cm3) as the primary endpoint along with 6-minute walk distance
      (6MWD, m), safety, and tolerability. Fifty-five (82.1%) patients completed the
      study. TMV increased by Week 4 and remained increased at Week 24 in bimagrumab
      treated patients, whereas no changes were observed with placebo (Week 4: +5.9%
      [3.4%, SD] vs. 0.0% [3.3%], P<0.001; Week 8: +7.0% [3.7%] vs. -0.7% [2.8%],
      P<0.001; Week 16: +7.8% [5.1%] vs. -0.9% [4.5%], P<0.001; Week 24: +5.0% [4.9%]
      vs. -1.3% [4.3%], P<0.001). Over 24 weeks, 6MWD did not increase significantly in
      either group. Adverse events in bimagrumab group included muscle-related
      symptoms, diarrhea, and acne, most of which were mild in severity. CONCLUSIONS:
      Blocking the action of negative muscle regulators through the activin type II
      receptors with bimagrumab treatment safely increased skeletal muscle mass but did
      not improve functional capacity in patients with COPD and low muscle mass.
      Clinical trial registration available at www.clinicaltrials.gov, ID NCT01669174.

PMID- 30095982
TI  - Targeting Intracellular Ion Homeostasis for the Control of Respiratory Syncytial
      Virus.
AB  - Respiratory syncytial virus (RSV) is a leading cause of mortality in infants and
      young children. Despite the RSV disease burden, no vaccine is available, and
      treatment remains nonspecific. New drug candidates are needed to combat RSV.
      Toward this goal, we screened over 2,000 compounds to identify approved drugs
      with novel anti-RSV activity. Cardiac glycosides, inhibitors of the membrane
      bound Na+/K+-ATPase, were identified to have anti-RSV activity. Cardiac
      glycosides diminished RSV infection in human epithelial type 2 cells and in
      primary human airway epithelial cells grown at an air-liquid interface. Digoxin,
      a U.S. Food and Drug Administration-approved cardiac glycoside, was also able to
      inhibit infection of primary nasal epithelial cells with community isolates of
      RSV. Our results suggest that the antiviral effects of cardiac glycosides may be
      dependent on changes in the intracellular Na+ and K+ composition. Consistent with
      this mechanism, we demonstrated that the ionophoric antibiotics salinomycin,
      valinomycin, and monensin inhibited RSV in human epithelial type 2 cells and
      primary nasal epithelial cells. Our data indicate that the K+/Na+-sensitive steps
      in the RSV life cycle occur within the initial 4 hours of viral infection but do
      not include virus binding/entry. Rather, our findings demonstrated a negative
      effect on the RSV transcription and/or replication process. Overall, this work
      suggests that targeting intracellular ion concentrations offers a novel antiviral
      strategy.

PMID- 30095983
TI  - Provider-Focused Intervention to Promote Comprehensive Screening for Adolescent
      Idiopathic Scoliosis by Primary Care Pediatricians.
AB  - Screening can detect adolescent idiopathic scoliosis (AIS). The objective was to
      determine if computer-based simulation (CBS) and computerized clinical decision
      support systems (CCDSS) would improve primary care providers' AIS screening exams
      as noted in their documentation. All participants received AIS screening CBS
      training. Participants were then randomized to receive either CCDSS when an
      eligible patient was seen (intervention arm) or no further intervention
      (comparison arm). Eligible patients' documentation was analyzed looking for a
      complete AIS screening exam. Over the span of 17 weeks, 1051 eligible patients
      were seen; 468 by providers in the intervention arm, 583 in the comparison arm.
      In all, 292/468 (62%) of eligible patients seen in the intervention arm and 0/583
      (0%) in the comparison arm had a complete AIS screening exam documented. Compared
      with single CBS training alone, repeated exposure to CCDSS after CBS training
      resulted in improved documentation of the screening exam for AIS.

PMID- 30095984
TI  - Effects of Insulin Treatment with Glargine or Premixed Insulin Lispro Programs in
      Type 2 Diabetes Mellitus Patients: A Meta-analysis of Randomized Clinical Trials.
AB  - BACKGROUND: The purpose of this study was to compare the efficacy and safety of
      intensive insulin therapy (premixed insulin lispro vs. insulin glargine) in
      patients with type 2 diabetes mellitus (T2DM). METHODS: MEDLINE, EMBASE, the
      Cochrane Library, and www.clinicaltrials.gov were systematically searched for
      randomized clinical trials (RCTs) of patients with T2DM treated with either
      premixed insulin lispro or insulin glargine for a duration of 24 weeks. RESULTS:
      A total of 13 RCTs and 5401 patients were included in this study. In parallel
      trials and crossover trials, premixed insulin lispro was found to be superior to
      insulin glargine at reducing glycosylated hemoglobin (HbA1c) (parallel trials:
      weighted mean difference [WMD] -0.18%; 95% confidence interval [CI] -0.31 to 
      0.06; P = 0.004; crossover trials: WMD 0.37%; 95% CI -0.51 to -0.23; P <
      0.00001). Premixed insulin lispro resulted in more weight gain than insulin
      glargine (parallel trials: WMD +0.64 kg; 95% CI +0.14 to +1.15; P = 0.01;
      crossover trials: WMD +0.74 kg; 95% CI +0.19 to +1.29; P = 0.009), and premixed
      insulin lispro was associated with a higher risk of hypoglycemia than insulin
      glargine (parallel trials: odds ratio [OR] 1.20; 95% CI 1.06-1.36; P = 0.005;
      crossover trials: OR 2.24; 95% CI 1.45-3.46; P = 0.0003). CONCLUSIONS: Premixed
      insulin lispro provides a larger reduction in HbA1c and is associated with a
      significantly higher risk of hypoglycemia and greater weight gain in patients
      with T2DM. These findings may be helpful in selecting therapy for individual
      subjects.

PMID- 30095985
TI  - Dalangtan Saline Playa in a Hyperarid Region of Tibet Plateau: III. Correlated
      Multiscale Surface Mineralogy and Geochemistry Survey.
AB  - We report the first multiscale, systematic field-based testing of correlations
      between orbital scale advanced spaceborne thermal emission and reflection
      radiometer visible near-infrared (VNIR)/shortwave infrared (SWIR) reflectance and
      thermal infrared relative emissivity and outcrop scale Raman spectroscopy, VNIR
      reflectance, X-ray diffraction (XRD), and laser-induced breakdown spectroscopy
      (LIBS) mineralogy and chemistry in a saline dry lakebed. This article is one of
      three reports describing the evolution of salt deposits, meteorological record,
      and surface and subsurface salt mineralogy in Dalangtan, Qaidam Basin, a
      hyperarid region of the Tibet Plateau, China, as potential environmental,
      mineralogical, and biogeochemical analogs to Mars. We have successfully bridged
      remote sensing data to fine scale mineralogy and chemistry data. We have defined
      spectral end-members in the northwestern Qaidam Basin and classified areas within
      the study area on the basis of their spectral similarity to the spectral end
      members. Results of VNIR/SWIR classification reveal zonation of spectral units
      within three large anticlinal domes in the study area that can be correlated
      between the three structures. Laboratory Raman, VNIR reflectance, XRD, and LIBS
      data of surface mineral samples collected along a traverse over Xiaoliangshan
      (XLS) indicate that the surface is dominated by gypsum, Mg sulfates, Na sulfates,
      halite, and carbonates, with minor concentrations of illite present in most
      samples as well. Our results can be used as a first step toward better
      characterizing the potential of orbital reflectance spectroscopy as a method for
      mineral detection and quantification in salt-rich planetary environments, with
      the benefit that this technique can be validated on the ground using instruments
      onboard rovers.

PMID- 30095986
TI  - Radiographic Analysis of Glenoid Size and Shape After Arthroscopic Coracoid
      Autograft Versus Distal Tibial Allograft in the Treatment of Anterior Shoulder
      Instability.
AB  - BACKGROUND: The Latarjet procedure for autograft transposition of the coracoid to
      the anterior rim of the glenoid remains the most common procedure for
      reconstruction of the glenoid after shoulder instability. The anatomic glenoid
      reconstruction using distal tibial allograft has gained popularity and is
      suggested to better match the normal glenoid size and shape. However, concerns
      about decreased healing and increased resorption arise when an allograft bone is
      used. PURPOSE: To use radiological findings to evaluate the arthroscopic
      reconstruction of the glenoid with respect to the size, shape, healing, and
      resorption of coracoid autograft versus distal tibial allograft. STUDY DESIGN:
      Cohort study; Level of evidence, 3. METHODS: A retrospective review was performed
      of 48 consecutive patients who had an arthroscopic bony reconstruction of the
      glenoid (12 coracoid autograft, 36 distal tibial allograft), diagnosed anterior
      shoulder instability, and computed tomography (CT)-confirmed glenoid bone loss
      more than 20%. Coracoid autograft was performed only when tibial allograft was
      not accessible from a bone bank. Two fellowship-trained musculoskeletal
      radiologists reviewed pre- and postoperative CT scans at a minimum follow-up of 6
      months for the following: graft position, glenoid concavity, cross-sectional
      area, width, version, total area, osseous union, and graft resorption. Clinical
      outcome was noted in terms of instability, subluxation, and dislocation at a
      minimum follow-up of 2 years. Simple logistic regression, 2-tailed independent
      sample t tests, paired t tests, and Fisher exact tests were performed. RESULTS:
      Graft union was seen in 9 of the 12 patients (75%) who had coracoid autograft and
      34 of the 36 patients (94%) who had tibial allograft (odds ratio, 5.66; 95% CI,
      0.81-39.20; P = .08). The odds ratio comparing allograft to coracoid for overall
      resorption was 7.00 (95% CI, 1.65-29.66; P = .008). Graft resorption >=50% was
      seen in 3 (8%) of the patients who had tibial allograft and none of the patients
      who had coracoid autograft. Graft resorption less than 50% was seen in the
      majority of patients in both groups: 27 (73%) patients with tibial allograft and
      5 (42%) patients with coracoid autograft. No statistically significant difference
      was found between the 2 procedures regarding anteroposterior diameter of graft (
      P = .81) or graft cross-sectional area ( P = .93). However, a significant
      difference was observed in step formation between the 2 procedures ( P < .001).
      Two patients experienced subluxations in the coracoid group (16%) as well as 2
      patients in the tibial allograft group (6%) with a P value of .25. CONCLUSION:
      Arthroscopic anatomic glenoid reconstruction via distal tibial allograft showed
      similar bony union but higher resorption compared with coracoid autograft. Even
      so, no statistically significant difference was found between the 2 procedures
      regarding final graft surface area, the size of grafts, and the anteroposterior
      dimensions of the reconstructed glenoids. These short-term results suggest that
      distal tibial allografts can be used as an alternative to coracoid autograft in
      the recreation of glenoid bony morphologic features.

PMID- 30095987
TI  - Dynamical and Biological Panspermia Constraints Within Multi-planet Exosystems.
AB  - As discoveries of multiple planets in the habitable zone of their parent star
      mount, developing analytical techniques to quantify extrasolar intra-system
      panspermia will become increasingly important. Here, we provide user-friendly
      prescriptions that describe the asteroid impact characteristics which would be
      necessary to transport life both inwards and outwards within these systems within
      a single framework. Our focus is on projectile generation and delivery and our
      expressions are algebraic, eliminating the need for the solution of differential
      equations. We derive a probability distribution function for life-bearing debris
      to reach a planetary orbit, and describe the survival of micro-organisms during
      planetary ejection, their journey through interplanetary space, and atmospheric
      entry.

PMID- 30095989
TI  - ??-????? ?? ??? : Sidney Blatt? ???-??? ?? (Congnitive-Humanistic Psychodynamics
      : Sidney Blatt's Theoretical-Philosophical Legacy).
AB  - ( ?? ) ??? ???-??? ???? Blatt? ????? ??? ??? ?????? ???. ?? ?? ?? ???? (1) ??, ??
      ??? ?? ??? ??? ?? ??; (2) ?????? ???? ?? (???, ????, ??? ?? ??, ????, ?? ?? ???
      ?? ???); (3) ????? ?? ??? ???? ?? ??? ??, ??? ??? ? ?? ???. ??? ????, Blatt? '??
      ????? ????'??? ????, ??? ??? ??? ???? ???? ???.

PMID- 30095988
TI  - Alveolar Micromechanics in Bleomycin-induced Lung Injury.
AB  - Lung injury results in intratidal alveolar recruitment and derecruitment and
      alveolar collapse, creating stress concentrators that increase strain and
      aggravate injury. In this work, we sought to describe alveolar micromechanics
      during mechanical ventilation in bleomycin-induced lung injury and surfactant
      replacement therapy. Structure and function were assessed in rats 1 day and 3
      days after intratracheal bleomycin instillation and after surfactant replacement
      therapy. Pulmonary system mechanics were measured during ventilation with
      positive end-expiratory pressures (PEEPs) between 1 and 10 cm H2O, followed by
      perfusion fixation at end-expiratory pressure at airway opening (Pao) values of
      1, 5, 10, and 20 cm H2O for quantitative analyses of lung structure. Lung
      structure and function were used to parameterize a physiologically based,
      multicompartment computational model of alveolar micromechanics. In healthy
      controls, the numbers of open alveoli remained stable in a range of Pao = 1-20 cm
      H2O, whereas bleomycin-challenged lungs demonstrated progressive alveolar
      derecruitment with Pao < 10 cm H2O. At Day 3, ~40% of the alveoli remained closed
      at high Pao, and alveolar size heterogeneity increased. Simulations of injured
      lungs predicted that alveolar recruitment pressures were much greater than the
      derecruitment pressures, so that minimal intratidal recruitment and derecruitment
      occurred during mechanical ventilation with a tidal volume of 10 ml/kg body
      weight over a range of PEEPs. However, the simulations also predicted a dramatic
      increase in alveolar strain with injury that we attribute to alveolar
      interdependence. These findings suggest that in progressive lung injury, alveolar
      collapse with increased distension of patent (open) alveoli dominates alveolar
      micromechanics. PEEP and surfactant substitution reduce alveolar collapse and
      dynamic strain but increase static strain.

PMID- 30095990
TI  - Microterracettes in Sabkha Oum Dba (Western Sahara, Morocco): Physical and
      Biological Interactions in the Formation of a Surface Micromorphology.
AB  - Small-scale terracing (microterracettes) is a surface geomorphic feature that
      recurs under a range of environmental settings, such as those existing in high to
      low temperature geothermal springs and evaporitic environments, through the
      single or combined action of physicochemical agents and microbiological
      processes. Such morphology can also be observed in a confined sector of the
      Sabkha Oum Dba, which is an inland sabkha of the Western Sahara (Morocco), where
      field and laboratory investigations revealed that they primarily depend on the
      accumulation of naviculoid diatoms. Through their biofilm production ability,
      these benthic diatoms are able to stabilize surface morphologies and make organic
      alveolar frameworks where the precipitation of low Mg calcite occurs in areas
      subjected to active oxygenic photosynthesis. Because microterracettes arise in a
      specific set of environmental conditions, they have environmental significance
      and, thanks to a high fossilization potential due to mineral precipitation, they
      can be an effective source of biomorphological and chemical evidence for life.
      The relationship with aqueous environments, considered to be widespread on Mars
      especially during a period of intense hydrologic activity as in the late Noachian
      and Hesperian periods, make the understanding of surficial processes useful (such
      as the formation of microterracettes) whose formation is frequent in terrestrial
      analogues for martian environments, such as ephemeral saline continental lakes
      (sabkhas) and related to the products of bacterial and eukaryotic life, as in the
      case of biofilms, in search for similar life forms beyond Earth.

PMID- 30095991
TI  - Interpretation of Transpulmonary Pressure Measurements in a Patient with Acute
      Life-Threatening Pulmonary Edema.

PMID- 30095992
TI  - Multilayer flow modulator enhances vital organ perfusion in patients with type B
      aortic dissection.
AB  - Management of aortic dissections (AD) is still challenging, with no universally
      approved guideline among possible surgical, endovascular, or medical therapies.
      Approximately 25% of patients with AD suffer postintervention malperfusion
      syndrome or hemodynamic instability, with the risk of sudden death if left
      untreated. Part of the issue is that vascular implants may themselves induce flow
      disturbances that critically impact vital organs. A multilayer mesh construct
      might obviate the induced flow disturbances, and it is this concept we
      investigated. We used preintervention and post-multilayer flow modulator
      implantation (PM) geometries from clinical cases of type B AD. In-house
      semiautomatic segmentation routines were applied to computed tomography images to
      reconstruct the lumen. The device was numerically reconstructed and adapted to
      the PM geometry concentrically fit to the true lumen centerline. We also
      numerically designed a pseudohealthy case, where the geometry of the aorta was
      extracted interpolating geometric features of preintervention, postimplantation,
      and published representative healthy volunteers. Computational fluid dynamics
      methods were used to study the time-dependent flow patterns, shear stress
      metrics, and perfusion to vital organs. A three-element Windkessel lumped
      parameter module was coupled to a finite-volume solver to assign dynamic outlet
      boundary conditions. Multilayer flow modulator not only significantly reduced
      false lumen blood flow, eliminated local flow disturbances, and globally
      regulated wall shear stress distribution but also maintained physiological
      perfusion to peripheral vital organs. We propose further investigation to focus
      the management of AD on both modulation of blood flow and restoration of
      physiologic end-organ perfusion rather than mere restoration of vascular lamina
      morphology. NEW & NOTEWORTHY The majority of aortic dissection modeling efforts
      have focused on the maintenance of physiological flow using minimally invasive
      placed grafts. The multilayer flow modulator is a complex mesh construct of
      wires, designed to eliminate flow disruptions in the lumen, regulate the
      physiological wall stresses, and enhance endothelial function and offering the
      promise of improved perfusion of vital organs. This has never been fully proved
      or modeled, and these issues we confirmed using a dynamic framework of time
      varying arterial waveforms.

PMID- 30095993
TI  - Can a Vitamin a Day Keep Tuberculosis Away?

PMID- 30095994
TI  - Chemical and Optical Identification of Micrometer-Sized 1.9 Billion-Year-Old
      Fossils by Combining a Miniature Laser Ablation Ionization Mass Spectrometry
      System with an Optical Microscope.
AB  - The recognition of biosignatures on planetary bodies requires the analysis of the
      putative microfossil with a set of complementary analytical techniques. This
      includes localized elemental and isotopic analysis of both, the putative
      microfossil and its surrounding host matrix. If the analysis can be performed
      with spatial resolution at the micrometer level and ppm detection sensitivities,
      valuable information on the (bio)chemical and physical processes that influenced
      the sample material can be gained. Our miniaturized laser ablation ionization
      mass spectrometry (LIMS)-time-of-flight mass spectrometer instrument is a valid
      candidate for performing the required chemical analysis in situ. However, up
      until now it was limited by the spatial accuracy of the sampling. In this
      contribution, we introduce a newly developed microscope system with micrometer
      accuracy for Ultra High Vacuum application, which allows a significant increase
      in the measurement capabilities of our miniature LIMS system. The new enhancement
      allows identification and efficient and accurate sampling of features of
      micrometer-sized fossils in a host matrix. The performance of our system is
      demonstrated by the identification and chemical analysis of signatures of
      micrometer-sized fossil structures in the 1.9 billion-year-old Gunflint chert.

PMID- 30095995
TI  - Respiratory Phenotypes during Childhood and Early Life Exposures.

PMID- 30095996
TI  - Cardiac myocyte proliferation and maturation near term is inhibited by early
      gestation maternal testosterone exposure.
AB  - Polycystic ovary syndrome (PCOS) is a complex and common disorder in women, and
      those affected experience an increased burden of cardiovascular disease. It is an
      intergenerational syndrome, as affected women with high androgen levels during
      pregnancy "program" fetal development, leading to a similar phenotype in their
      female offspring. The effect of excess maternal testosterone exposure on fetal
      cardiomyocyte growth and maturation is unknown. METHODS Pregnant ewes received
      biweekly injections of vehicle (Control) or 100 mg testosterone propionate
      between 30-59 days of gestation (dGA; Early T) or 60-90 dGA (Late T). Fetuses
      were delivered at ~135 dGA and their hearts enzymatically dissociated to measure
      cardiomyocyte growth (dimensional measurements), maturation (proportion
      binucleate), and proliferation (nuclear Ki-67 protein). RESULTS Early T depressed
      serum insulin-like growth factor 1 (IGF-1) and caused intrauterine growth
      restriction (IUGR)(P<0.0005). Hearts were smaller in Early T (P<0.001) due to
      reduced cardiac myocyte maturation (P<0.0005) and proliferation (P=0.017).
      Maturation was also less in males than in females (P=0.004), independent of
      treatment. Late T did not affect cardiac growth. CONCLUSIONS Early excess
      maternal testosterone exposure depresses circulating IGF-1 near term and causes
      IUGR in both female and male offspring. These fetuses have small, immature hearts
      with reduced proliferation, which may reduce cardiac myocyte endowment and
      predispose to adverse cardiac growth in postnatal life. While excess maternal
      testosterone exposure leads to PCOS and cardiovascular disease in female
      offspring, it may also predispose to complications of IUGR and cardiovascular
      disease in male offspring.

PMID- 30095997
TI  - PTEN Inhibitor VO-OHpic Attenuates Inflammatory M1 Macrophages and Cardiac
      Remodeling in Doxorubicin-Induced Cardiomyopathy.
AB  - Doxorubicin (Doxo) is an effective agent commonly used in cancer therapeutics.
      Unfortunately, Doxo treatment can stimulate cardiomyopathy and subsequent heart
      failure, limiting use of this drug. The role of phosphatase and tensin homolog
      (PTEN) in apoptosis has been documented in Doxo induced cardiomyopathy (DIC) and
      heart failure models. However, whether direct inhibition of PTEN attenuates
      apoptosis, cardiac remodeling, and inflammatory M1 macrophages in DIC model
      remains elusive. Therefore, the current study is designed to understand effects
      of VO-OHpic (VO), a potent inhibitor of PTEN, in reducing apoptosis and cardiac
      remodeling. At D56, echocardiography was performed, which shows VO-OHpic
      treatment significantly (p<0.05) improves heart function. Immunohistochemistry,
      TUNEL, and histological staining were used to determine apoptosis, pro
      inflammatory M1 macrophages, anti-inflammatory M2 macrophages, and cardiac
      remodeling. Our data shows a significant increase in apoptosis, hypertrophy,
      fibrosis, and pro-inflammatory M1 macrophages with Doxo treatment, whereas VO
      treatment significantly reduced apoptosis, adverse cardiac remodeling, and pro
      inflammatory M1 macrophages significantly (p<0.05) compared to Doxo group.
      Western blotting confirmed the reduction of p-PTEN and increase in p-AKT protein
      expression in the Doxo+VO group. Moreover, VO administration increased anti
      inflammatory M2 macrophages. Collectively, our data suggests that VO-OHpic
      treatment attenuates apoptosis and adverse cardiac remodeling, a process that is
      mediated through PTEN/AKT pathway, resulting in improved heart function in DIC.

PMID- 30095998
TI  - Pulmonary endothelial cells exhibit sexual dimorphism in their response to
      hyperoxia.
AB  - Abnormal pulmonary vascular development is a critical factor in the pathogenesis
      of bronchopulmonary dysplasia (BPD). Despite the well-established sex-specific
      differences in the incidence of BPD, the molecular mechanism(s) behind these are
      not completely understood. Exposure to high concentration of oxygen (hyperoxia)
      contributes to BPD and creates a pro-fibrotic environment in the lung. Our
      objective was to elucidate the sex-specific differences in neonatal human
      pulmonary microvascular endothelial cells (HPMECs) in normoxic and hyperoxic
      conditions including propensity for endothelial to mesenchymal transition. HPMECs
      (18-24 weeks gestation donors; 6 male and 5 female) were subjected to hyperoxia
      (95% O2 and 5% CO2) or normoxia (air and 5% CO2) up to 72 h. We assessed cell
      migration and angiogenesis at baseline. Cell proliferation, viability, and
      expression of endothelial (CD31) and fibroblast markers (alpha-SMA) were measured
      upon exposure to hyperoxia. Female HPMECs had significantly higher cell migration
      when assessed by the wound healing assay (40.99 +/- 4.4 %) compared to male
      (14.76 +/- 3.7 %) and showed greater sprouting (1710 +/- 962 MUm in female vs 789
      +/- 324 in male) compared to male endothelial cells in normoxia. Hyperoxia
      exposure decreased cell viability (by 9.8% at 48h and 11.7% at 72h) and
      proliferation (by 26.7% at 72 h) markedly in male HPMECs, while viability was
      sustained in female endothelial cells. There was greater expression of alpha-SMA
      (2.5-fold) and decreased expression (5-fold) of CD31 in male HPMECs, upon
      exposure to hyperoxia. The results indicate that cellular sex affects response in
      HPMECs in normoxia and hyperoxia.

PMID- 30095999
TI  - Leg Blood Flow and Skeletal Muscle Microvascular Perfusion Responses to
      Submaximal Exercise in Peripheral Arterial Disease.
AB  - Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of
      the lower limb arteries. While leg blood flow is limited in PAD, it remains
      unclear whether skeletal muscle microvascular perfusion is affected. We compared
      whole-leg blood flow and calf muscle microvascular perfusion following cuff
      occlusion and submaximal leg exercise between PAD patients (n=12, 69+/-9 years)
      and healthy age-matched control participants (n=12, 68+/-7 years). Microvascular
      blood flow (microvascular volume x flow velocity) of the medial gastrocnemius
      muscle was measured before and immediately after: 1) 5 min of thigh-cuff
      occlusion; and 2) a 5-min bout of intermittent isometric plantar-flexion exercise
      (400N) using real-time contrast-enhanced ultrasound (CEU). Whole-leg blood flow
      was measured after thigh-cuff occlusion and during submaximal plantar-flexion
      exercise using strain-gauge plethysmography. Post-occlusion whole-leg blood flow
      and calf muscle microvascular perfusion were lower in PAD patients than controls,
      and these parameters were strongly correlated (r=0.84; p<0.01). During submaximal
      exercise, total whole-leg blood flow and vascular conductance were not different
      between groups. There were also no group differences in post-exercise calf muscle
      microvascular perfusion, although microvascular blood volume was higher in PAD
      patients than control (12.41+/-6.98 vs 6.34+/-4.98 aU; p=0.03). This study
      demonstrates that the impaired muscle perfusion of PAD patients during post
      occlusion hyperemia is strongly correlated with disease severity, and is likely
      mainly determined by the limited conduit artery flow. In response to submaximal
      leg exercise, microvascular flow volume was elevated in PAD patients, which may
      reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery
      during recovery from exercise.

PMID- 30096000
TI  - Construction, Expression, and Characterization of a Novel Human-Mouse Chimeric
      Antibody, Hm3A4: A Potential Therapeutic Agent for B and Myeloid Lineage
      Leukemias.
AB  - Antibody-targeting therapy has drawn great interests to the hematologists and
      oncologists. 3A4, a novel antibody recognizing human CD45RA antigen, is a new
      target molecule for leukemias and holds a therapeutic potential for myeloid
      lineage leukemias. However, murine antibodies cannot be safely used in patients
      because of their strong immune reaction, humanization of the antibodies
      interested will be an important development step for therapeutic purpose. The aim
      of this study was to engineer the mouse 3A4 and to investigate the biological
      activity of its chimeric form. The humanized antibody composed of the 3A4 single
      chain fragment of variable region and the human IgG1 Fc region, which was named
      human-mouse chimeric antibody 3A4 (Hm3A4). The function and biological activities
      of Hm3A4 were characterized using a variety of biological approaches. The results
      showed that Hm3A4 retained a strong binding activity to its antigen and could
      significantly block the binding of parental 3A4 to the antigen. In vitro
      experiments revealed that Hm3A4 could kill the target cells through complement
      dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity
      function. In vivo, Hm3A4 showed efficient antileukemia activity outperforming the
      nontreated mice. In conclusion, the chimeric antibody has an excellent biological
      activity after humanization and holds targeting therapeutic potential for myeloid
      leukemia, which warrants further development of this agent.

PMID- 30096001
TI  - Topical Quercetin and Resveratrol Protect the Ocular Surface in Experimental Dry
      Eye Disease.
AB  - PURPOSE: To determine the anti-inflammatory effect of quercetin (QCT),
      resveratrol (RES), and their combination in a dry eye disease (DED) model.
      METHODS: 0.01% QCT, 0.1% RES, 0.01% QCT + 0.1% RES (QCT + RES) or vehicle were
      topically applied in a desiccating stress (DS) mice model. CD4+ T cells isolated
      from DS-exposed mice were transferred to athymic recipient mice. Corneal
      fluorescein staining, tear production, and tear cytokine levels were evaluated in
      DS-exposed mice, and conjunctival CD4+ T cell infiltration was evaluated in
      recipient mice. RESULTS: QCT (p < 0.001) and QCT + RES (p < 0.05) reduced corneal
      staining in DS-exposed mice. IL-1alpha tear concentration was reduced by QCT,
      RES, and QCT + RES (p < 0.05, 0.01 and 0.01, respectively) compared to DS +
      vehicle mice. CD4+ T cells increased in recipients of DS-exposed mice (p < 0.05)
      and were lower in recipients of QCT- and RES-treated mice (p < 0.05). CONCLUSION:
      The anti-inflammatory effect of QCT, RES, and QCT + RES on DED-experimental model
      suggests that their topical application could be used for DED treatment.

PMID- 30096002
TI  - Automation Expectation Mismatch: Incorrect Prediction Despite Eyes on Threat and
      Hands on Wheel.
AB  - OBJECTIVE:: The aim of this study was to understand how to secure driver
      supervision engagement and conflict intervention performance while using highly
      reliable (but not perfect) automation. BACKGROUND:: Securing driver engagement-by
      mitigating irony of automation (i.e., the better the automation, the less
      attention drivers will pay to traffic and the system, and the less capable they
      will be to resume control) and by communicating system limitations to avoid
      mental model misconceptions-is a major challenge in the human factors literature.
      METHOD:: One hundred six drivers participated in three test-track experiments in
      which we studied driver intervention response to conflicts after driving highly
      reliable but supervised automation. After 30 min, a conflict occurred wherein the
      lead vehicle cut out of lane to reveal a conflict object in the form of either a
      stationary car or a garbage bag. RESULTS:: Supervision reminders effectively
      maintained drivers' eyes on path and hands on wheel. However, neither these
      reminders nor explicit instructions on system limitations and supervision
      responsibilities prevented 28% (21/76) of drivers from crashing with their eyes
      on the conflict object (car or bag). CONCLUSION:: The results uncover the
      important role of expectation mismatches, showing that a key component of driver
      engagement is cognitive (understanding the need for action), rather than purely
      visual (looking at the threat), or having hands on wheel. APPLICATION::
      Automation needs to be designed either so that it does not rely on the driver or
      so that the driver unmistakably understands that it is an assistance system that
      needs an active driver to lead and share control.

PMID- 30096003
TI  - Robotic Right Colectomy for Colon Cancer: Comparison of Outcomes from a Single
      Institution with the ACS-NSQIP Database.
AB  - BACKGROUND: Robotic surgery has increased in recent years for the treatment of
      colorectal cancer; however, it is not yet the standard of care. This study aims
      to compare the 30-day outcomes after robotic colectomy for right-sided colon
      cancer from our institution with those from a national dataset, the targeted
      colectomy American College of Surgeons National Surgical Quality Improvement
      Program (ACS-NSQIP) database. METHODS: Patients undergoing elective, robotic,
      right colon resection for stage I, II, and III colon cancer were identified
      within the targeted colectomy ACS-NSQIP database from 2012 to 2014. Patients
      meeting the same criteria were identified within a prospectively maintained
      institutional database from 2009 to 2015. Univariate analyses using chi-square
      tests and Student's t-tests were done where appropriate to compare baseline
      characteristics and outcomes between the two groups. RESULTS: Patients at our
      institution had a significantly higher average number of lymph nodes retrieved
      (24.4 versus 20.1, P = .046). There was no statistically significant difference
      between the two groups regarding the incidence of wound infections, anastomotic
      leaks, blood transfusions, unplanned return to the operating room, or prolonged
      length of hospital stay. There were no 30-day mortalities at our institution and
      only one in the ACS-NSQIP database. CONCLUSIONS: Our institutional experience
      with robotic right colon resection is equivalent to that of a national sample.
      This study demonstrates the safety of performing robotic right hemicolectomy for
      the treatment of colon cancer.

PMID- 30096004
TI  - Role of Ultra-Wide-Field Imaging in the Diagnosis of Intravitreal
      Gnathostomiasis: A Case-Report.

PMID- 30096005
TI  - Disparities in Adolescent and Young Adult Sarcoma Survival: Analyses of the Texas
      Cancer Registry and the National SEER Data.
AB  - PURPOSE: Examine disparities in survival for adolescents and young adults (AYAs)
      diagnosed with bone and soft tissue sarcomas in Texas compared with national
      estimates. METHODS: AYAs with sarcomas diagnosed between 1995 and 2012 at ages 15
      39 years were identified from the Texas Cancer Registry (TCR) and Surveillance,
      Epidemiology, and End Results (SEER) program. Patient demographic, treatment, and
      clinical characteristics were compared between TCR and SEER using chi-squared
      tests. Five-year survival was computed using the Kaplan-Meier method. Cox
      proportional hazards (CPH) models evaluated the factors associated with the risk
      of mortality between and within the two datasets. RESULTS: Sarcoma patients in
      TCR were more likely to be Hispanic, uninsured, diagnosed at late stage, and have
      lower rates of surgery as the first line of treatment than those in SEER. In
      Texas, 5-year survival was 68.7% versus 72.2% in SEER (p < 0.001). However, after
      including surgery in our fully adjusted CPH model, survival differences between
      the two datasets were no longer observed. In these models, males, and those
      living in nonmetropolitan areas were more likely to die than their counterparts
      in both datasets. In TCR, those who lived in the U.S. and Mexico border had
      higher mortality. In SEER, Hispanics and non-Hispanic blacks had higher
      mortality. CONCLUSION: The adjusted AYA sarcoma survival in Texas was similar to
      that of SEER, but patients in Texas were more likely to be uninsured and have
      lower surgery rates. Those living in the U.S. and Mexico border in Texas faced
      lower survival. These results are important for delineating effective care for
      this high-risk patient group.

PMID- 30096006
TI  - Inward- and outward-facing homology modeling of human concentrative nucleoside
      transporter 3 (hCNT3) predicts an elevator-type transport mechanism.
AB  - The human SLC28 family of concentrative (Na+-dependent) nucleoside transporters
      has three members, hCNT1, hCNT2 and hCNT3. Previously, we have used heterologous
      expression in Xenopus laevis oocytes in combination with an engineered cysteine
      less hCNT3 protein hCNT3(C-) to undertake systematic substituted cysteine
      accessibility method (SCAM) analysis of the transporter using the membrane
      impermeant thiol reactive reagent p-chloromercuribenzene sulfonate (PCMBS). A
      continuous sequence of more than 300 individual amino acid residue positions were
      investigated, including the entire transport domain of the protein, as well as
      important elements of the corresponding hCNT3 structural domain. We have now
      constructed 3D structural homology models of hCNT3 based upon inward-facing,
      intermediates and outward-facing crystal structures of the bacterial CNT
      Neisseria wadsworthii CNTNW to show that all previously identified PCMBS
      sensitive residues in hCNT3 are located above (ie on the extracellular side of)
      the key diagonal barrier scaffold domain TM9 in the transporter's outward-facing
      conformation. In addition, both the Na+ and permeant binding sites of the mobile
      transport domain of hCNT3 are elevated from below the scaffold domain TM9 in the
      inward-facing conformation to above TM9 in the outward-facing conformation. The
      hCNT3 homology models generated in the present study validate our previously
      published PCMBS SCAM data, and confirm an elevator-type mechanism of membrane
      transport.

PMID- 30096007
TI  - Thoracoscopic Cardiac Sympathetic Denervation: Adjunct Therapy for Secondary
      Prevention of Life-Threatening Ventricular Arrhythmias in Children.
AB  - BACKGROUND: Cardiac sympathetic denervation (CSD) is a surgical option for
      patients with life-threatening ventricular arrhythmias. Previously described
      cohorts included populations in which CSD was performed for primary and secondary
      prevention. We report the efficacy of CSD as adjunct therapy in children with
      medically refractory life-threatening arrhythmias. MATERIALS AND METHODS:
      Retrospective review of patients undergoing thoracoscopic CSD at one institution
      between January 2008 and July 2017. Patient demographics, indications, procedural
      details, complications, length of stay, and effectiveness were evaluated.
      RESULTS: Ten thoracoscopic CSD procedures were performed in 8 patients. Mean age
      was 8.2 years (8 days-19 years); mean weight was 32.6 kg (2.7-57 kg); and 50%
      were female. Four had long QT syndrome, 3 catecholaminergic polymorphic
      ventricular tachycardia, and 1 short QT syndrome. All patients had at least two
      (2 to >40) episodes of resuscitated ventricular arrhythmia and were maximized on
      medical therapy. Six patients had implantable cardioverter-defibrillators (ICD)
      with a mean of 11.9 appropriate discharges (1-40) before CSD. All patients
      underwent left CSD; 2 subsequently required right CSD. Four of the 6 ICD patients
      experienced dramatic improvement (total 48 ICD discharges pre-CSD; 3 post-CSD).
      Two patients noncompliant with medical therapy had no significant improvement (24
      ICD discharges pre-CSD; 23 post-CSD) and also underwent right CSD, again with no
      improvement (23 discharges pre-right CSD; 28 post-right CSD). CONCLUSIONS:
      Thoracoscopic CSD can be safely performed in the neonate and pediatric
      populations. When utilized with medication therapy, CSD is an effective adjunct
      in reducing ICD discharges and arrhythmias.

PMID- 30096008
TI  - Lack of Evidence for erm(B) Infiltration Into Erythromycin-Resistant
      Campylobacter coli and Campylobacter jejuni from Commercial Turkey Production in
      Eastern North Carolina: A Major Turkey-Growing Region in the United States.
AB  - In Campylobacter spp., resistance to erythromycin and other macrolides has
      typically implicated ribosomal mutations, especially substitutions in the 23S
      rRNA genes. However, in 2014, the macrolide resistance gene erm(B) was reported
      for the first time in Campylobacter and shown to be harbored by a multidrug
      resistance island in the chromosome of the swine-derived strain Campylobacter
      coli ZC113. erm(B)-positive C. coli and Campylobacter jejuni strains from the
      food supply have been mostly reported from China. However, erm(B)-positive C.
      coli isolates were also detected recently in fecal samples from turkeys in Spain.
      To determine whether erm(B) may be harbored by erythromycin-resistant
      Campylobacter from commercial turkey production in eastern North Carolina, a
      major turkey-growing region in the United States, we investigated a panel of 178
      erythromycin-resistant isolates (174 C. coli, 4 C. jejuni) using PCR with erm(B)
      specific primers. None of the isolates were PCR-positive for erm(B) and sequence
      analysis of a subset of these erythromycin-resistant isolates revealed that all
      harbored A2075G substitutions in the 23S rRNA genes. Data fail to provide
      evidence for infiltration of erm(B) into erythromycin-resistant Campylobacter
      from commercial turkey production in this region and suggest the need for
      continuing surveillance.

PMID- 30096009
TI  - Optical Coherence Tomography and Management of a Retinal Granuloma in Presumed
      Ocular Sarcoidosis.
AB  - PURPOSE: To highlight the utility of EDI-OCT and periocular steroid
      administration for the treatment of a retinal granuloma due to presumed ocular
      sarcoidosis. METHODS: Retrospective case-study of a single patient. RESULTS: A 45
      year-old African-American male with blurred vision in the right eye was found to
      have a macula-involving retinal granuloma. Laboratory, imaging, and clinical
      findings were consistent with a diagnosis of presumed ocular sarcoidosis. Optical
      coherence tomography (OCT) and fundus photographs were used to document granuloma
      evolution. Oral prednisone 60mg was initiated and tapered to 10mg within 2
      months. Due to systemic side-effects and inadequate treatment response with
      prednisone, 5 sub-Tenon's triamcinolone acetonide (PSTA) injections were then
      administered over 7 months, and oral prednisone was discontinued at 6 months.
      CONCLUSION: This case demonstrated marked granuloma regression occurring with
      improvement in visual acuity, highlighting the utility of OCT and PSTA in
      managing retinal sarcoid granulomas.

PMID- 30096011
TI  - Ocular Involvement in Systemic Lupus Erythematosus: The Experience of Two
      Tertiary Referral Centers.
AB  - PURPOSE: To assess the prevalence of the ocular manifestations related to the
      disease and/or ascribable to the administration of potentially toxic drugs in a
      cohort of 98 patients with systemic lupus erythematosus (SLE). METHODS:
      Retrospective, observational study reporting the experience of two tertiary
      referral centers. RESULTS: Overall, an ocular involvement was detected in 29
      patients (29.6%), sometimes preceding of months the diagnosis of SLE, more often
      revealed at diagnosis or throughout its course. More than a single ocular
      manifestation was found in 20 of the 29 patients with ophthalmological findings
      (68.9%). The array of ocular morbidity included, in a decreasing order of
      frequency, cataracts, keratoconjunctivitis sicca, glaucoma, discoid lesions of
      eyelids, episcleritis, retinopathy, vortex keratopathy, choroidopathy and retinal
      detachment, central retinal vein occlusion, and hydroxychloroquine-induced toxic
      maculopathy. CONCLUSIONS: It is advised that a multidisciplinary team for the
      diagnosis and treatment of SLE should regularly include the presence of an
      ophthalmologist.

PMID- 30096010
TI  - Avoidable Mortality: The Core of the Global Cancer Divide.
AB  - Purpose The incidence of infection-associated cancers and lethality of cancers
      amenable to treatment are closely correlated with the income of countries. We
      analyzed a core part of this global cancer divide-the distribution of premature
      mortality across country income groups and cancers-applying novel approaches to
      measure avoidable mortality and identify priorities for public policy. Methods We
      analyzed avoidable cancer mortality using set lower- and upper-bound age limits
      of 65 and 75 years (empirical approach), applying cancer-specific and country
      income group-specific ages of death (feasibility approach), and applying cancer
      specific ages of death of high-income countries to all low- and middle-income
      countries (LMICs; social justice approach). We applied these methods to 2015
      mortality data on 16 cancers for which prevention is possible and/or treatment is
      likely to result in cure or significant increase in life expectancy. Results At
      least 30% and as much as 50% of cancer deaths are premature, corresponding to
      between 2.6 and 4.3 million deaths each year, and 70% to 80% are concentrated in
      LMICs. Using the feasibility approach, 36% of cancer deaths are avoidable; with
      the social justice approach, 45% of cancer deaths are avoidable. Five cancer
      types-breast, colorectal, lung, liver, and stomach-account for almost 75% of
      avoidable cancer deaths in LMICs and worldwide. Conclusion Each year, millions of
      premature cancer deaths could be avoided with interventions focused on four
      priority areas: infection-associated cancers, lifestyle and risk factors, women's
      cancers, and children's cancers. Our analysis of the global burden and the
      specific cancer types associated with avoidable cancer mortality suggests
      significant opportunities for health systems to redress the inequity of the
      global cancer divide.

PMID- 30096012
TI  - Anti-CD20 monoclonal antibodies: reviewing a revolution.
AB  - Since the inception of rituximab in the 1990s, anti-CD20 monoclonal antibodies
      have revolutionised the treatment of B cell hematological malignancies and have
      become a cornerstone of modern gold-standard practice. Additionally, the potent
      efficacy of these agents in depleting the B cell compartment has been used in the
      management of a broad array of autoimmune diseases. Multiple iterations of these
      agents have been investigated and are routinely used in clinical practice. In
      this review, we will discuss the physiology of CD20 and its attractiveness as a
      therapeutic target, as well as the pharmacology, pre-clinical and clinical data
      for the major anti-CD20 monoclonal antibodies: rituximab, obinutuzumab and
      ofatumumab.

PMID- 30096013
TI  - INFLIXIMAB and ADALIMUMAB in Uveitic Macular Edema.
AB  - PURPOSE: To compare the efficacy of infliximab and adalimumab in patients with
      refractory uveitis-related macular edema (ME). METHODS: A retrospective study was
      conducted in all patients with refractory uveitis-related ME treated with
      infliximab or adalimumab in Pitie-Salpetriere hospital between January 1, 2006
      and January 1, 2016. All patients underwent a complete ophthalmologic
      examination, OCT and retinal angiography at baseline, and 6 (M6) and 24 months
      (M24) after treatment initiation. Main outcome was a decrease in central foveal
      thickness (CFT) on OCT. RESULTS: Twenty-five patients were included: 12 treated
      with adalimumab and 13 treated with infliximab. The median baseline CFT was 381
      MUm (Q1 = 254; Q3 = 470) in the adalimumab group and 469 MUm (307; 539) in the
      infliximab group. At M6, 6/12 adalimumab-treated patients (50%) and 8/13
      infliximab-treated patients (61%) were responders. The median CFT decrease from
      baseline was 61 MUm (17-136) and 66 MUm (-59-119) respectively at M6 and M24 in
      the adalimumab group versus 92 MUm (9-165) and 52 MUm (33-130) respectively at M6
      and M24 in the infliximab group (all p > 0.05). CONCLUSION: No significant
      difference in efficacy was observed between infliximab and adalimumab at M6 and
      M24.

PMID- 30096014
TI  - Fermented Ganjangs (Soy Sauce and Sesame Sauce) Attenuates Colonic Carcinogenesis
      in Azoxymethane/Dextran Sodium Sulfate-Treated C57BL/6J Mice.
AB  - The effects of different ganjangs (also designated as kanjang), including acid
      hydrolyzed soy sauce (AHSS), fermented soy sauce (FSS), and fermented sesame
      sauce (FSeS), on azoxymethane (AOM, 10 mg/kg)/dextran sulfate sodium (DSS, 2%)
      induced colorectal carcinogenesis in C57BL/6J mice were studied. Low doses (4
      mL/kg) of both FSeS and FSS significantly increased colon length, suppressed
      AOM/DSS-induced increases in colon weight/length ratios, and induced colorectal
      neoplasia compared with AHSS-treated and control mice. Fermented sauces,
      particularly low doses of FSeS and FSS, showed activity against AOM/DSS-induced
      colorectal carcinogenesis by abrogating serum and mRNA levels of tumor necrosis
      factor-alpha, interferon-gamma, interleukin (IL)-6, and IL-17alpha as well as by
      reducing mRNA levels of inducible nitric oxide synthase and cyclooxygenase-2 in
      colon mucosa. FSeS significantly increased colonic p53 expression compared with
      other sauces. However, AHSS showed weak activity against AOM/DSS-induced colonic
      carcinogenesis. Overall, FSeS showed the strongest anticancer effect, followed by
      FSS and AHSS. Thus, fermentation with microorganisms rather than chemical
      processes is important, and raw materials are another factor influencing
      anticancer activity.

PMID- 30096015
TI  - Review for Disease of the Year: Treatment of Viral Anterior Uveitis: A
      Perspective.
AB  - PURPOSE: To define a clinically tailored therapeutic strategy for the treatment
      of viral anterior uveitis (VAU). METHODS: A PubMed search spanning the past 5
      years was conducted using the MesH-terms "viral anterior uveitis" and "therapy."
      RESULTS: The herpes simplex virus (HSV), the varicella zoster virus (VZV), and
      the cytomegalovirus (CMV) are the predominant pathogens in VAU. Other viruses,
      including rubella, chikungunya, and zika, have been linked with distinct forms of
      the disease. Depending on the causative agent and the host immunocompetence, the
      mainstay treatment for suspected VAU is a combination of topical or systemic
      antivirals and topical corticosteroids, supplemented with cycloplegics and
      intraocular-pressure-lowering medication. CONCLUSIONS: Oral acyclovir,
      valacyclovir, and famciclovir are the mainstay of treatment for HSV- and VZV
      induced infections. Brivudin serves as an alternative in insufficiently
      responsive cases. CMV-induced infections respond well to valganciclovir. A 3- to
      12-month course of prophylactic treatment against recurrences is worth
      considering.

PMID- 30096016
TI  - Public Health Implications of Housing Laws: Nuisance Evictions.

PMID- 30096018
TI  - Familiar Voices Are More Intelligible, Even if They Are Not Recognized as
      Familiar.
AB  - We can recognize familiar people by their voices, and familiar talkers are more
      intelligible than unfamiliar talkers when competing talkers are present. However,
      whether the acoustic voice characteristics that permit recognition and those that
      benefit intelligibility are the same or different is unknown. Here, we recruited
      pairs of participants who had known each other for 6 months or longer and
      manipulated the acoustic correlates of two voice characteristics (vocal tract
      length and glottal pulse rate). These had different effects on explicit
      recognition of and the speech-intelligibility benefit realized from familiar
      voices. Furthermore, even when explicit recognition of familiar voices was
      eliminated, they were still more intelligible than unfamiliar voices
      demonstrating that familiar voices do not need to be explicitly recognized to
      benefit intelligibility. Processing familiar-voice information appears therefore
      to depend on multiple, at least partially independent, systems that are recruited
      depending on the perceptual goal of the listener.

PMID- 30096017
TI  - Effects of Rickettsia amblyommatis Infection on the Vector Competence of
      Amblyomma americanum Ticks for Rickettsia rickettsii.
AB  - Although Dermacentor spp. ticks are considered the primary vectors of Rickettsia
      rickettsii in the United States, other North American tick species are also
      capable of transmitting the agent, including the lone star tick-Amblyomma
      americanum. The lone star tick is an aggressive human-biting tick abundant in the
      South, Central, and Mid-Atlantic United States, which has been shown to be a
      competent vector of R. rickettsii in laboratory studies. However in nature, A.
      americanum frequently carry Rickettsia amblyommatis-another member of the spotted
      fever group-with the prevalence of infection reaching 84% in some populations. It
      has been postulated that the presence of an endosymbiotic Rickettsia in a
      significant proportion of a vector population would diminish or even block
      transmission of pathogenic Rickettsia in ticks from generation to generation due
      to transovarial interference. We measured the ability of R. amblyommatis-infected
      A. americanum to acquire R. rickettsii from an infected host with a bloodmeal,
      and transmit it transstadially, horizontally (to a susceptible host), and
      vertically to the next generation. Larvae from both the R. amblyommatis-infected
      and R. amblyommatis-free cohorts acquired R. rickettsii from infected guinea
      pigs, but the presence of the symbiont diminished the ability of coinfected
      engorged larvae to transmit R. rickettsii transstadially. Conversely, acquisition
      of R. rickettsii by cofeeding was unaffected in R. amblyommatis-infected nymphs
      and adults; prevalence of R. rickettsii in engorged adults reached 97% in both R.
      amblyommatis-infected and R. amblyommatis-free cohorts. In guinea pigs exposed to
      dually infected nymphs, R. rickettsii infection was milder than in those fed upon
      nymphs infected with R. rickettsii only. The frequency of transovarial
      transmission of R. rickettsii in the R. amblyommatis-infected cohort (31%)
      appeared lower than that in the R. amblyommatis-free cohort (48%), but the
      difference was not statistically significant. Larval progenies of dually infected
      A. americanum females transmitted R. rickettsii to naive guinea pigs confirming
      viability of the pathogen. Thus, the vector competence of A. americanum for R.
      rickettsii was not significantly affected by R. amblyommatis.

PMID- 30096019
TI  - First Report of 'Candidatus Phytoplasma asteris' Associated with Witches' Brooms
      on Sharp-Flowered Rush (Juncus acutiflorus) in Poland.

PMID- 30096020
TI  - First Report of Alfalfa Leaf Curl Virus Affecting Alfalfa (Medicago sativa) in
      Jordan, Lebanon, Syria, and Tunisia.

PMID- 30096021
TI  - Synthetic Turf: History, Design, Maintenance, and Athlete Safety.
AB  - CONTEXT: Synthetic turf has become an increasingly common playing surface for
      athletics and has changed dramatically since its introduction more than 50 years
      ago. Along with changes to surface design, maintenance needs and recommendations
      have become more standardized and attentive both to upkeep and player-level
      factors. In particular, synthetic turf maintenance as it relates to athlete
      health and safety is an important consideration at all levels of play. EVIDENCE
      ACQUISITION: A literature search of MEDLINE and PubMed for publications between
      the years 1990 and 2018 was conducted. Keywords included s ynthetic turf,
      artificial turf, field turf, and playing surface. Additionally, expert opinion
      through systematic interviews and practical implementation were obtained on
      synthetic turf design and maintenance practices in the National Football League.
      STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 5. RESULTS: Synthetic
      turf has changed considerably since its inception. Playing surface is a critical
      component of the athletic environment, playing a role both in performance and in
      athlete safety. There are several important structural considerations of third
      generation synthetic turf systems currently used in the United States that rely
      heavily on strong and consistent maintenance. A common misconception is that
      synthetic turf is maintenance free; in fact, however, these surfaces require
      routine maintenance. Whether athletes experience more injuries on synthetic over
      natural surfaces is also of interest among various levels and types of sport.
      CONCLUSION: Modern synthetic turf is far different than when originally
      introduced. It requires routine maintenance, even at the level of local
      athletics. It is important for sports medicine personnel to be familiar with
      playing surface issues as they are often treating athletes at the time of injury
      and should maintain a level of awareness of contemporary research and practices
      regarding the relationships between synthetic turf and injury.

PMID- 30096022
TI  - Consistency of State Statutes and Regulations With Centers for Disease Control
      and Prevention's 2006 Perinatal HIV Testing Recommendations.

PMID- 30096024
TI  - Identifying the inserted locus of randomly integrated expression plasmids by
      whole-genome sequencing of Aspergillus strains.
AB  - Whole-genome sequencing was conducted on two Aspergillus oryzae strains used for
      the manufacturing of food enzymes, Acrylaway(r) and Shearzyme(r), with the aim of
      identifying the inserted locus of randomly integrated expression plasmid and
      obtaining flanking sequences for safety assessment. Illumina paired-end
      sequencing was employed, and the obtained reads were mapped to two references:
      the public genome sequence of Aspergillus oryzae RIB40 and the in-house sequence
      of the used expression plasmid. Introducing the concept of linking-reads, one
      locus for each was successfully identified as the integrated site. In the case of
      Acrylaway(r), the obtained sequences suggested that the expression plasmid had
      been integrated as multiple copies in tandem form. In the case of Shearzyme(r),
      however, information on one edge of the insert was missing, which required extra
      polymerase chain reaction (PCR) cloning for safety assessment. A 4-kb deletion
      was detected at the integrated site. There was also evidence of rearrangement
      occurring in Shearzyme(r) strain.

PMID- 30096023
TI  - Recent Patterns of Multimorbidity Among Older Adults in High-Income Countries.
AB  - Population aging along with the rising burden of chronic medical conditions
      (CMCs) is challenging the sustainability of health care systems globally. The
      authors sought to characterize contemporary patterns of multimorbidity among
      older adults (aged >=65 years) in high-income countries (HICs). Medline, EMBASE,
      CINAHL, PsycINFO, and Web of Science were searched in January 2018 for English
      language articles that reported the prevalence of multimorbidity (defined as co
      occurrence of >=2 CMCs in an individual without defining an index disease) among
      older adults in HICs, or the proportions with >=3 or >=5 CMCs. Only studies that
      utilized data collected during January 2007-December 2017 were included. A total
      of 52 articles (45 studies) that reported data among >60 million older adults in
      30 HICs were included. The overall prevalence of multimorbidity was 66.1%
      (interquartile range [IQR] 54.4-76.6). The multimorbidity prevalence increased
      with age as well as with the number of CMCs included in the assessment. The
      prevalence of >=3 or >=5 CMCs was 44.2% (IQR 34.0-70.3) and 12.3% (IQR 8.7-19.1),
      respectively. The multimorbidity prevalence was also higher among females as well
      as among studies using care-based data rather than self-reported data. The
      prevalence of hypertension, dyslipidemia, diabetes, pain disorders, depression,
      heart failure, cancer, and dementia among the older adults was 60.6%, 51.2%,
      25.2%, 34.0%, 12.0%, 14.0%, 8.6%, and 8.4%, respectively. The available data
      suggest a high prevalence of multimorbidity among older adults. There is a need
      for increased research into understanding the causal mechanisms that underlie
      multimorbidity toward supporting the development of cost-effective interventions.
      In addition, the study results reiterate the need for preventive health care to
      move beyond targeting single diseases in favor of directing efforts toward
      reducing overall morbidity among this population.

PMID- 30096025
TI  - Increasing Access to High Value Care: Preventing Complications in Common
      Disorders.
AB  - Most infantile hemangiomas (IHs), the most common vascular tumors of childhood,
      evolve without complications; however 10% to 12% require specialty referral for
      treatment. To emphasize the complications of late referral, we present a case of
      necrotizing infection within a segmental IH leading to sepsis. Early evaluation
      by a pediatric dermatologist could have prevented this life-threatening and
      disfiguring complication. We discuss how teledermatology would enable rapid
      triage of such critical cases in underserved areas, increasing access to high
      value care and optimizing outcomes for our most vulnerable patients.

PMID- 30096028
TI  - Clostridial Enterotoxemia and Coccidiosis in Weanling Cottontail Rabbits (
      Sylvilagus audubonii, Sylvilagus floridanus, Sylvilagus nuttallii) from Colorado,
      USA.
AB  - Wild cottontail rabbits ( Sylvilagus spp.), especially young individuals, are one
      of the most frequent wildlife species presented for rehabilitation at wildlife
      rehabilitation centers. These species are challenging to rehabilitate, with
      gastrointestinal (GI) disease being a major cause of morbidity and mortality
      during the weaning stage. Two organisms, Clostridium spiroforme and Eimeria spp.,
      are frequently associated with GI disease in young domestic rabbits ( Oryctolagus
      cuniculus) and can result in high rates of morbidity and mortality in this
      species. Here we present evidence that these two pathogens also play an important
      role in GI disease in young cottontail rabbits ( Sylvilagus audubonii, Sylvilagus
      floridanus, Sylvilagus nuttallii) undergoing rehabilitation.

PMID- 30096027
TI  - Mortality, Ethnicity, and Urbanization Among Children Aged 1-4 Years on the US
      Mexico Border.
AB  - OBJECTIVES: Little is known about the mortality of children along the US-Mexico
      border. The objective of our study was to determine whether mortality rates among
      Hispanic children along the border ("border Hispanic children") exceeded
      mortality rates among non-Hispanic white children along the border. METHODS: We
      examined mortality rates from 2001-2015 for children aged 1-4 years in US-Mexico
      border counties and in the United States overall. We compared mortality rates
      among Hispanic and non-Hispanic white children by county urbanization level
      (large central, medium, and small metropolitan; micropolitan nonmetropolitan; and
      noncore nonmetropolitan). RESULTS: During 2001-2015, 1811 children aged 1-4 years
      died in the border region. The mortality rate per 100 000 children among border
      Hispanic children (28.3; 95% confidence interval [CI], 26.8-29.9) exceeded the
      mortality rate of US Hispanic children (24.7; 95% CI, 24.3-25.1) and border non
      Hispanic white children (23.2; 95% CI, 20.8-25.6). When stratified by county
      urbanization level, however, mortality rates of border Hispanic children were not
      significantly different from mortality rates of US Hispanic or border non
      Hispanic white children. Mortality rates in noncore nonmetropolitan counties were
      twice those in large central metropolitan counties, with injury mortality
      accounting for most of the excess. Mortality rates increased in nonmetropolitan
      border counties after 2010. CONCLUSIONS: Increased risk for injury and disease in
      noncore nonmetropolitan counties might be related to poverty, reduced access to
      care, or poorer quality of care. Future research should identify the remediable
      risk factors in such communities as the next step in preventing deaths among
      children aged 1-4 years.

PMID- 30096029
TI  - Mortality Due to Toxoplasmosis in Suburban Eastern Fox Squirrels ( Sciurus niger)
      in Michigan, USA.
AB  - Three separate mortality events affecting wild eastern fox squirrels ( Sciurus
      niger) were investigated in suburban areas within southeastern Michigan over a 3
      yr period from the summer of 2015 through the winter of 2017. A total of seven
      squirrels were submitted for investigation. The squirrels were generally in fair
      to good body condition with moderate fat deposits. The tissues that most commonly
      exhibited gross or histologic lesions included the lungs, liver, and heart,
      whereas spleen and brain exhibited lesions less frequently. Lung lesions in all
      seven squirrels consisted of moderate interstitial pneumonia with necrosis and
      moderate to high numbers of protozoal organisms. Livers in four out of seven
      squirrels had multifocal necrosis associated with low to moderate numbers of
      protozoal organisms. Three out of seven brains examined had mild nonsuppurative
      meningoencephalitis with widely scattered protozoal cysts. Protozoal organisms
      observed in various tissues were strongly immunoreactive to Toxoplasma gondii
      antibody by immunohistochemical staining. Other primary disease conditions tested
      for included West Nile virus infection, pesticides, and anticoagulants.
      Toxoplasma gondii can cause disease and mortality in a variety of wild squirrel
      species, especially near human settlements, and would merit more attention.

PMID- 30096026
TI  - Perinatal HIV Service Coordination: Closing Gaps in the HIV Care Continuum for
      Pregnant Women and Eliminating Perinatal HIV Transmission in the United States.
AB  - Eliminating perinatal transmission of HIV and improving the care of childbearing
      women living with HIV in the United States require public health and clinical
      leadership. The Comprehensive Care Workgroup of the Elimination of Perinatal HIV
      Transmission Stakeholders Group, sponsored by the Centers for Disease Control and
      Prevention, developed a concept of perinatal HIV service coordination (PHSC) and
      identified 6 core functions through (1) semistructured exploratory interviews
      with contacts in 11 state or city health departments from April 2011 through
      February 2012, (2) literature review and summary of data on gaps in services and
      outcomes, and (3) group meetings from August 2010 through June 2017. We discuss
      leadership strategies for implementing the core functions of PHSC: strategic
      planning, access to services, real-time case finding, care coordination,
      comprehensive care, and data and case reviews. PHSC provides a systematic
      approach to optimize services and close gaps in perinatal HIV prevention and the
      HIV care continuum for childbearing women that can be individualized for
      jurisdictions with varying needs.

PMID- 30096030
TI  - Serosurvey for Influenza Virus Subtypes H3N8 and H3N2 Antibodies in Free-Ranging
      Canids in Pennsylvania, USA.
AB  - Canine influenza virus (CIV) subtypes H3N8 and H3N2 are endemic among domestic
      dog (XXXX XXXXX) populations in the northeastern US. Infection of free-ranging
      carnivores with influenza virus has been sporadically reported. Generalist
      mesocarnivores that exploit anthropogenic, peri-urban habitats share a wide
      interface with domestic dogs that allows for the transmission of infectious
      disease. To investigate the potential exposure of free-ranging canids to CIV in
      Pennsylvania, US, serum samples were obtained from freshly killed coyotes ( Canis
      latrans, n=67), grey foxes ( Urocyon cinereoargenteus, n=8), and red foxes (
      Vulpes vulpes, n=5) from 24 counties. Animals were harvested during the January
      February 2017 hunting season. We failed to detect antibodies to CIV subtypes H3N2
      and H3N8 by using hemagglutination inhibition assays validated for domestic dogs.
      Results suggest CIV was not endemic in free-ranging canid populations in
      Pennsylvania or that prevalence was too low to be detected by our limited sample
      size.

PMID- 30096031
TI  - Neospora caninum DNA in Coyote Fecal Samples Collected in an Urban Environment.
AB  - Definitive hosts of Neospora caninum are species of canids, such as domestic dogs
      ( Canis lupus familiaris), coyotes ( Canis latrans) and foxes (XXXXXXX), whereas
      ruminants, such as cattle ( Bos taurus), sheep ( Ovis aries), and deer (Cervidae)
      serve as intermediate hosts. We investigated the presence of N. caninum in feces
      of coyotes in Calgary, Alberta, Canada. One hundred coyote fecal samples were
      collected from five city parks. Following DNA extraction, the presence of N.
      caninum DNA was determined by using real-time PCR analysis with a primer and
      probe pair targeting the Nc5 gene. Ten of the 100 samples contained detectable
      amounts of N. caninum DNA. White-tailed deer ( Odocoileus virginianus) and mule
      deer ( Odocoileus hemionus) are common in Calgary's city parks, and although we
      did not examine them for the presence of N. caninum bradyzoites, the presence of
      N. caninum DNA in coyote fecal samples is indicative that a sylvatic host of N.
      caninum exists within this urban environment.

PMID- 30096032
TI  - Regional and Age-Related Variations in Haptoglobin Concentrations in Steller Sea
      Lions ( Eumetopias jubatus) from Alaska.
AB  - Varying concentrations of the highly conserved acute phase response protein,
      haptoglobin, can indicate changes to the health and disease status of mammals,
      including the Steller sea lion ( Eumetopias jubatus; SSL). To better understand
      factors relating to acute phase response in SSLs, circulating haptoglobin
      concentrations (Hp) were quantified in plasma collected from 1,272 individuals
      sampled near rookeries and haulouts off the coast of Alaska. We compared Hp in
      SSLs between sexes and among different age classes (young pups, young-of-the
      year, yearlings, subadults, and adults) sampled within distinct regions in Alaska
      (Aleutian Islands, Gulf of Alaska, Southeast Alaska). Regional and age-related
      differences were observed, particularly in younger SSLs. No sex-related
      differences were detected. We identified weakly significant relationships between
      Hp and hematology measurements including white blood cell counts (WBC) and
      hematocrit (Hct) in young pups from the Aleutian Islands and Southeast Alaska. No
      relationship between Hp and body condition was found. Lastly, a nonlinear
      relationship of plasma Hp and whole blood total mercury concentrations (THg) was
      observed in SSLs from the endangered western distinct population segment in
      Alaska. These results demonstrated that regional variation in Hp, especially in
      younger SSLs, may reflect regional differences in health and circulating THg.

PMID- 30096033
TI  - Ectoparasitism in Black-and-White Ruffed Lemurs ( Varecia variegata) in
      Southeastern Madagascar.
AB  - We documented ectoparasites found on wild black-and-white ruffed lemurs ( Varecia
      variegate) in the southeastern rain forests of Madagascar and describe trends in
      parasitism. In this study, 235 mesostigmatic mites (1 male, 87 females, 147
      nymphs) identified as Liponyssella sp., in the acarine family Macronyssidae, were
      collected during 87% (34/39) of lemur examinations (mean number/host=7.9). The
      only other ectoparasite collected was the louse fly ( Allobosca crassipes) in the
      dipteran family Hippoboscidae, which was collected (3 males, 8 females) during
      26% (10/39) of lemur examinations (mean number/host=1.1). The lemur most heavily
      parasitized by mites was an adult female with 29 adult females and 17 nymphs, all
      collected from the face.

PMID- 30096034
TI  - Detection of Bisgaard Taxon 40 in Rhinoceros Auklets ( Cerorhinca monocerata)
      with Pneumonia and Septicemia from a Mortality Event in Washington.
AB  - We isolated Bisgaard taxon 40 from Rhinoceros Auklets ( Cerorhinca monocerata)
      with pneumonia and septicemia from Washington, US, found dead in 2016. Previously
      isolated only from the respiratory tract of a gull (Laridae), little is known
      about its pathogenic potential and whether it acts as a primary or opportunistic
      pathogen.

PMID- 30096035
TI  - Expanded Molecular Typing of Sarcoptes scabiei Provides Further Evidence of
      Disease Spillover Events in the Epidemiology of Sarcoptic Mange in Australian
      Marsupials.
AB  - The invasive ectoparasite Sarcoptes scabiei affects the welfare and conservation
      of Australian marsupials. Molecular data suggest that spillover from other hosts
      may be responsible for the emergence of this infectious disease, but the scale of
      such studies is limited. We performed expanded molecular typing of the S. scabiei
      mitochondrial cox1 gene from 81 skin scrapings from infested wombats ( Vombatus
      ursinus), koalas ( Phascolarctos cinereus), red foxes ( Vulpes vulpes), and dogs
      ( Canis lupus familiaris) across Australia. Combined with existing S. scabiei
      sequences, our analysis revealed 16 haplotypes among Australian animals, sharing
      between 93.3% and 99.7% sequence similarity. While some sequences were unique to
      specific hosts or to Australia, key haplotypes could be detected across several
      marsupial hosts as well as to wild or domestic canids in Australia. We identified
      43 cox1 haplotypes with many Australian haplotypes identical to S. scabiei mites
      from inside and outside Europe. We concluded that multiple introduction events
      were plausible explanations to the origin and emergence of this parasite into
      Australian marsupials and that disease spillover from canids was likely.
      Together, our greatly expanded S. scabiei sequence dataset provided a more
      nuanced picture of both spillover and sustained intraspecific transmission for
      this important parasite.

PMID- 30096037
TI  - Alpha-1 Antitrypsin Deficiency as a Candidate for Gene Editing.

PMID- 30096036
TI  - Fibropapillomatosis in a Green Sea Turtle ( Chelonia mydas) from the Southeastern
      Pacific.
AB  - Fibropapillomatosis is a neoplastic disease that afflicts sea turtles. Although
      it is disseminated worldwide, cases of the disease have not been reported in the
      southeastern Pacific region. We describe a case of fibropapillomatosis in a green
      sea turtle ( Chelonia mydas) during its rehabilitation at the Machalilla National
      Park Rehabilitation Center, Ecuador. Viral presence was confirmed by PCR,
      targeting fragments of the chelonid alphaherpesvirus 5 (ChHV5) unique long (UL)
      genes, UL27, UL28, and UL30. The amplicons were sequenced and included in a
      global phylogenetic analysis of the virus with other reported sequences from
      GenBank. Results showed that the available viral sequences segregated into five
      phylogeographic groups: western Atlantic and eastern Caribbean, central Pacific,
      western Pacific, Atlantic, and eastern Pacific groups. The concatenated ChHV5
      sequences from Ecuador clustered with the eastern Pacific sequences.

PMID- 30096038
TI  - Dietary epicatechin improves survival and delays skeletal muscle degeneration in
      aged mice.
AB  - We recently reported that epicatechin, a bioactive compound that occurs naturally
      in various common foods, promoted general health and survival of obese diabetic
      mice. It remains to be determined whether epicatechin extends health span and
      delays the process of aging. In the present study, epicatechin or its analogue
      epigallocatechin gallate (EGCG) (0.25% w/v in drinking water) was administered to
      20-mo-old male C57BL mice fed a standard chow. The goal was to determine the
      antiaging effect. The results showed that supplementation with epicatechin for 37
      wk strikingly increased the survival rate from 39 to 69%, whereas EGCG had no
      significant effect. Consistently, epicatechin improved physical activity, delayed
      degeneration of skeletal muscle (quadriceps), and shifted the profiles of the
      serum metabolites and skeletal muscle general mRNA expressions in aging mice
      toward the profiles observed in young mice. In particular, we found that dietary
      epicatechin significantly reversed age-altered mRNA and protein expressions of
      extracellular matrix and peroxisome proliferator-activated receptor pathways in
      skeletal muscle, and reversed the age-induced declines of the nicotinate and
      nicotinamide pathway both in serum and skeletal muscle. The present study
      provides evidence that epicatechin supplementation can exert an antiaging effect,
      including an increase in survival, an attenuation of the aging-related
      deterioration of skeletal muscles, and a protection against the aging-related
      decline in nicotinate and nicotinamide metabolism.-Si, H., Wang, X., Zhang, L.,
      Parnell, L. D., Admed, B., LeRoith, T., Ansah, T.-A., Zhang, L., Li, J., Ordovas,
      J. M., Si, H., Liu, D., Lai, C.-Q. Dietary epicatechin improves survival and
      delays skeletal muscle degeneration in aged mice.

PMID- 30096039
TI  - Endothelin-1 differentially directs lineage specification of adipose- and bone
      marrow-derived mesenchymal stem cells.
AB  - Blood vessels composed of endothelial cells (ECs) contact with mesenchymal stem
      cells (MSCs) in different tissues, suggesting possible interaction between these
      2 types of cells. We hypothesized that endothelin-1 (ET1), a secreted paracrine
      factor of ECs, can differentially direct the lineages of adipose-derived stem
      cells (ASCs) and bone marrow-derived MSCs (BMSCs). Predifferentiated ASCs and
      BMSCs were treated with ET1 for 2 cell passages and then induced for multilineage
      differentiation. Our results showed that adipogenesis of ET1-pretreated ASCs and
      osteogenesis of ET1-pretreated BMSCs were increased compared to those of control
      cells. The effect of ET1 on enhancing adipogenesis of ASCs and osteogenesis of
      BMSCs was attenuated by blocking endothelin receptor type A (ETAR) and/or
      endothelin receptor type B (ETBR). Western blot analysis indicated that
      regulation by ET1 was mediated through activation of the protein kinase B and
      ERK1/2 signaling pathways. We analyzed subpopulations of ASCs and BMSCs with or
      without ETAR and/or ETBR, and we found that ETAR+/ETBR- and ETAR-/ETBR+
      subpopulations of ASCs and those of BMSCs pretreated with ET1 were prone to
      turning into adipocytes and osteoblasts, respectively, after differentiation
      induction. Our findings provide insight into the differential regulation of MSC
      specification by ET1, which may help develop viable approaches for tissue
      regeneration.-Lee, M.-S., Wang, J., Yuan, H., Jiao, H., Tsai, T.-L., Squire, M.
      W., Li, W.-J. Endothelin-1 differentially directs lineage specification of
      adipose- and bone marrow-derived mesenchymal stem cells.

PMID- 30096040
TI  - Residual cyclooxygenase activity of aspirin-acetylated COX-2 forms 15 R
      prostaglandins that inhibit platelet aggregation.
AB  - Aspirin (acetylsalicylic acid) inhibits prostaglandin (PG) synthesis by transfer
      of its acetyl group to a serine residue in the cyclooxygenase (COX) active site.
      Acetylation of Ser530 inhibits catalysis by preventing access of arachidonic acid
      substrate in the COX-1 isoenzyme. Acetylated COX-2, in contrast, gains a new
      catalytic activity and forms 15 R hydroxy-eicosatetraenoic acid (15 R-HETE) as
      alternate product. Here we show that acetylated COX-2 also retains COX activity,
      forming predominantly 15 R-configuration PGs (70 or 62% 15 R, respectively,
      determined using radiolabeled substrate or LC-MS analysis). Although the Km of
      arachidonic acid for acetylated COX-2 was ~3-fold lower than for uninhibited COX
      2, the catalytic efficiency for PG formation by the acetylated enzyme was reduced
      10-fold due to a concomitant decrease in Vmax. Aspirin increased 15 R-PGD2 but
      not 15 R-PGE2 in isolated human leukocytes activated with LPS to induce COX-2. 15
      R-PGD2 inhibited human platelet aggregation induced by the thromboxane receptor
      agonist U46,619, and this effect was abrogated by an antagonist of the DP1
      prostanoid receptor. We conclude that acetylation of Ser530 in COX-2 not only
      triggers formation of 15 R-HETE but also allows oxygenation and cyclization of
      arachidonic acid to a 15 R-PG endoperoxide. 15 R-PGs are novel products of
      aspirin therapy via acetylation of COX-2 and may contribute to its antiplatelet
      and other pharmacologic effects.-Gimenez-Bastida, J. A., Boeglin, W. E., Boutaud,
      O., Malkowski, M. G., Schneider, C. Residual cyclooxygenase activity of aspirin
      acetylated COX-2 forms 15 R-prostaglandins that inhibit platelet aggregation.

PMID- 30096041
TI  - Letter to the Editor: "Dysplasia Should Not Be Ignored in Lichenoid Mucositis".

PMID- 30096042
TI  - Dysplasia and Lichenoid Mucositis: The Chicken or the Egg?

PMID- 30096044
TI  - Executive Summary of Key Concepts.

PMID- 30096043
TI  - Wheat gluten hydrolysate potently stimulates peptide-YY secretion and suppresses
      food intake in rats.
AB  - The study was aimed to compare the satiating effect of various protein
      hydrolysates in rats and examine the underlying mechanism associated with the
      satiety hormones. Food intake and portal satiety hormone levels were measured in
      rats. Enteroendocrine cell-lines were employed to study the direct effect of
      protein hydrolysates on gut hormone secretions. The results showed that oral
      preload of wheat gluten hydrolysate (WGH) suppressed food intake greater and
      longer than other hydrolysates. The portal peptide-YY levels in WGH-treated rats
      at 2 h and 3 h were higher than those in control- and lactalbumin hydrolysate
      (LAH)-treated rats. In a distal enteroendocrine cell model, WGH more potently
      stimulated glucagon-like peptide-1 secretion than LAH, and the effect was largely
      enhanced by pepsin/pancreatin digestion of WGH. These results suggest WGH is
      potent in activating enteroendocrine cells to release satiety hormones leading to
      the prolonged suppression of food intake.

PMID- 30096046
TI  - Designing for Public Health With Healthcare Design Part II: Design.

PMID- 30096047
TI  - Content and Intent.

PMID- 30096048
TI  - Anodic reactions of NADH model compound by utilizing both light irradiation and
      riboflavin as a redox mediator.
AB  - Both light and a redox mediator riboflavin (RF) were utilized to promote the
      electro-oxidation of an NADH model compound (1-benzyl-1,4-dihydronicotinamide,
      BNAH), which is a key process for enzymatic biofuel cells to obtain a high
      performance. At the cathode, H+ ions were simultaneously reduced to produce H2
      gas. To elucidate the cell reactions of this photogalvanic cell, which is
      significant information about the fabrication of enzymatic biofuel cells with a
      high performance, the effect of the BNAH and RF concentrations on the cell
      current, the light wavelength dependence on the current, and reduction of the RF
      concentration were evaluated. The obtained results strongly suggest that the
      anodic reactions were composed of the following reactions: 1) the photo
      excitation of RF, 2) the attack of the excited RF on the BNAH and the generation
      of the radical species of BNAH and RF, and 3) the chain reactions between the
      radical species.

PMID- 30096049
TI  - Imaging Evaluation of Pediatric Parotid Gland Abnormalities.
AB  - Parotid gland lesions in children can be divided into benign or malignant. The
      age of the patient helps narrow the differential diagnosis, with vascular and
      congenital lesions being more frequent in the 1st year of life, while solid
      tumors are more frequent in older children. Inflammatory disease usually has
      rapid onset in comparison with that of neoplastic or congenital processes, which
      have more gradual clinical evolution. Currently, multiple imaging techniques are
      available to study the parotid region, such as US, CT, and MRI. However, it is
      still a challenge to distinguish nonmalignant lesions from malignant ones. US is
      the first-line diagnostic approach in children to characterize the morphology and
      vascularity of these lesions. CT in children may be indicated for evaluation of
      abscesses or sialolithiasis. MRI is the imaging modality of choice for
      investigating the nature of the lesion and its extent. In addition to complete
      and detailed clinical information, knowledge of parotid gland anatomy and
      characteristic radiologic features of parotid disorders is essential for optimal
      radiologic evaluation and avoiding unnecessary interventional diagnostic
      procedures or treatment. This article illustrates a variety of entities
      (congenital, inflammatory, vascular, neoplastic) that can occur in the parotid
      gland, highlighting the most frequent radiologic patterns of manifestation and
      correlating them with clinical, surgical, and pathologic findings. (c)RSNA, 2018.

PMID- 30096050
TI  - Radiology Resident Assessment and Feedback Dashboard.
AB  - Assessment of residents is optimally performed through processes and platforms
      that provide daily feedback, which can be immediately acted on. Given the
      documentation required by the Accreditation Council for Graduate Medical
      Education (ACGME), effective data management, integration, and presentation are
      crucial to ease the burden of manual documentation and increase the timeliness of
      actionable information. To this end, the authors modeled the learning activities
      of residents using the Experience Application Programming Interface (xAPI)
      framework, which is a standard framework for the learning community. On the basis
      of the xAPI framework and using open-source software to extend their existing
      infrastructure, the authors developed a Web-based dashboard that provides
      residents with a more holistic view of their educational experience. The
      dashboard was designed around the ACGME radiology milestones and provides real
      time feedback to residents using various assessment metrics derived from multiple
      data sources. The purpose of this article is to describe the dashboard's
      architecture and components, the design and technical considerations, and the
      lessons learned in implementing the dashboard. (c)RSNA, 2018.

PMID- 30096051
TI  - Therapeutic Drug Monitoring of Levetiracetam in Select Populations.
AB  - PURPOSE: Levetiracetam (LEV) is a broad spectrum antiepileptic drug (AED) that
      has a more favorable side effect profile compared to older AEDs. Therapeutic drug
      monitoring (TDM) of LEV is generally unnecessary given its linear and predictable
      dose-serum concentration relationship, lack of drug-drug interactions, and broad
      therapeutic window. However, there is growing evidence showing that alteration of
      LEV pharmacokinetics (PK) may occur in special populations calling for the need
      for TDM. The purpose of this review was to summarize current literature
      surrounding altered LEV PK in special patient populations and determine if there
      is a need for levetiracetam TDM. METHODS: A literature search of MEDLINE (1946 -
      November 2017) database of available evidence pertaining to altered LEV PK in
      humans was conducted. RESULTS: A total of 51 articles were found.  There has not
      been a positive correlation shown between LEV levels and efficacy or toxicity.
      Variable LEV levels are reported in the literature with respect to adverse
      effects, seizures and efficacy occurring below, within and above the supposed
      reference ranges. Age is a major contributor to altered pharmacokinetics of LEV
      as shown in elderly patients and pediatric patients. Compared to adults,
      clearance of LEV has been shown to be decreased by almost half in patients over
      65 and increased by 30-40% in pediatric patients. LEV pharmacokinetics varied
      further when data from its use in neonates was explored. LEV clearance declined
      in a linear fashion with declining estimates of creatinine clearance but was
      variable in patients with end-stage renal failure or those requiring renal
      replacement therapy. In patients who were critically ill, LEV clearance may be
      augmented and these patients may require higher doses of medications to maintain
      drug levels. In patients who are pregnant, LEV levels are likely to decline as
      pregnancy progresses due to changes in glomerular filtration rate and remain
      variable in the post-partum period. CONCLUSION: Routine TDM of levetiracetam is
      not recommended for all populations, however, it may be beneficial to maintain an
      individual therapeutic range in patients where the PK of LEV may be altered, such
      as in patients who are critically ill patients, pregnant, pediatrics or elderly.

PMID- 30096053
TI  - 'Author's Response to Letter to the Editor On 'Ultrasound-Guided Botulinum Toxin
      Injections in Cervical Dystonia Needs Prompt Muscle Selection, Appropriate Dosage
      and Precise Guidance'.

PMID- 30096052
TI  - Managing inappropriate utilization of laboratory resources.
AB  - Background The inappropriate use of laboratory resources, due to excessive number
      of tests not really necessary for patient care or by failure to order the
      appropriate diagnostic test, may lead to wrong, missed or delayed diagnosis, thus
      potentially jeopardizing patient safety. It is estimated that 5-95% of tests are
      currently used inappropriately, depending on the appropriateness criteria, thus
      significantly contributing to the potential of generating medical errors, the
      third leading cause of death in the US. Content In this review, we discuss the
      reasons as well as the medical and financial consequences of inappropriate
      utilization of laboratory tests. We then provide demand management (DM) tools as
      a means for overcoming this issue and also discuss their benefits, challenges,
      limitations and requirements for successful implementation. Summary and outlook
      When based on current evidence, adapted to local conditions and developed in
      close collaboration with clinicians, DM is a reasonable strategy for progressing
      toward better management of over- and underuse of laboratory resources.

PMID- 30096054
TI  - Maximizing Recovery From Concussions for Youth Participating in Sports and
      Recreational Activities.
AB  - Concussions have become a public health issue. This public health concern has
      drawn the attention of many states in which laws were created to address
      concussions safety, recognition of signs and symptoms, immediate removal, medical
      clearance, and return to play protocols. The vast majority of state legislation
      focused on student athletes participating in organized sports. However the rise
      in concussion can be directly attributed to children, youth and adolescents
      participating in non-sports related events. Maximizing recovery from a concussion
      involves implementing education programs that focus on recognition of symptoms,
      treatment, and return to learn options. Treatment strategies employed to address
      concussed youth include physical and cognitive rest and minimizing external
      stimuli that can increase symptoms. Since learning is a direct outcome for all
      youth, a return to learn protocol based on a collaborative school-based team
      approach is suggested.

PMID- 30096055
TI  - The Allergy Alert Test: Introduction of a Protocol Suitable to Provide an Alert
      Signal in p-Phenylenediamine-Allergic Hair Dye Users.
AB  - BACKGROUND: Contact dermatitis to hair dyes remains a health concern. Regulations
      in many countries require consumer self-testing for hair dyes, but no
      standardized procedure exists. OBJECTIVE: The aim of this study was to develop a
      self-test protocol for an allergy alert test (AAT) that can elicit a self
      noticeable alert signal in p-phenylenediamine (PPD)-allergic consumers. METHODS:
      Simulating consumer use conditions (open application after mixing with a
      developer for 45 minutes), PPD-positive hair dye-allergic subjects and PPD
      negative control subjects were tested on the forearm and behind the ear with
      experimental products containing 0.05%, 0.25%, 0.75%, and 2% PPD. Reactions were
      self-evaluated by subjects and independently assessed by dermatologists.
      CONCLUSIONS: The AAT caused a reaction self-noticeable on the forearm in 90.5%
      (38/42) and behind the ear in 93% (39/42) of the PPD-positive subjects. This was
      objectified by a dermatological evaluation. The strength of the AAT response and
      the number of responding subjects increased with increasing PPD concentrations.
      Allergy alert test responses were also dependent on the reaction strength of the
      diagnostic patch test to PPD before the study; in subjects with (+++) patch test
      reactions, 19 of 19 were positive. All 48 control subjects were negative to the
      AAT. Therefore, the AAT protocol provides a signal indicative of an allergic
      reaction in PPD-allergic hair dye consumers.This is an open-access article
      distributed under the terms of the Creative Commons Attribution-Non Commercial-No
      Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and
      share the work provided it is properly cited. The work cannot be changed in any
      way or used commercially without permission from the journal.

PMID- 30096056
TI  - The effect of selective serotonin reuptake inhibitors on major adverse
      cardiovascular events: a meta-analysis of randomized-controlled studies in
      depression.
AB  - It has been reported that selective serotonin reuptake inhibitors (SSRIs) might
      induce major adverse cardiovascular events (MACE), but the association between
      the use of SSRIs and MACE has not been elucidated as yet. Therefore, the aim of
      this study was to evaluate the association between the use of SSRIs and MACE in
      depressed patients with previous cardiovascular events. Two researchers
      independently selected randomized-controlled studies (RCTs) according to the
      predefined inclusion criteria and evaluated the quality of articles. A
      quantitative analysis was carried out to estimate pooled risk ratios (RRs) for
      the association between the use of SSRIs and MACE. Ten RCTs were selected in the
      final analysis. The use of SSRIs in depressed patients with previous
      cardiovascular events significantly decreased the risk of MACE [RR: 0.74; 95%
      confidence interval (CI): 0.55-0.99]. The risk of myocardial infarction was also
      reduced significantly (RR: 0.59, 95% CI: 0.37-0.93), associations with stroke and
      all-cause-death (cardiac or other causes): risk of stroke (RR: 0.88, 95% CI: 0.35
      2.25) or all-cause death (RR: 0.83; 95% CI: 0.66-1.05). This meta-analysis
      suggests that the use of SSRIs decreased the risk of MACE by significantly
      reducing the risk of myocardial infraction in patients with depression and
      previous cardiovascular events.

PMID- 30096057
TI  - On the utility of causal diagrams in modeling attrition: a practical example.

PMID- 30096058
TI  - Congenital Tuberculosis: A New Concern in the Neonatal Intensive Care Unit.
AB  - BACKGROUND: Congenital tuberculosis (TB) is rare in the United States. Recent
      immigration patterns to the United States have made the diagnosis of congenital
      TB an important public health issue. PURPOSE: To explore the epidemiology,
      pathophysiology, diagnostic evaluation, treatment, and prognosis for congenital
      TB. The implications for exposed healthcare professionals in the neonatal
      intensive care unit (NICU) setting are also explored. METHODS/SEARCH STRATEGY:
      Relevant articles were accessed via PubMed, CINAHL, and Google Scholar.
      FINDINGS/RESULTS: Until 1994, fewer than 400 cases of confirmed congenital TB had
      been reported in the literature worldwide. An additional 18 cases were reported
      from 2001 to 2005. Neonatal providers need to be aware of the potential for
      congenital TB infection as the immigrant population in the United States
      continues to increase, many of whom originate from TB endemic countries.
      IMPLICATIONS FOR PRACTICE: The interpretation of TB-specific tests is problematic
      in newborns due to decreased sensitivity and specificity. Congenital TB should be
      ruled out in infants with signs and symptoms of sepsis or pneumonia and in whom
      broad-spectrum antibiotic therapy does not improve their clinical status.
      IMPLICATIONS FOR RESEARCH: The interpretation of TB-specific tests is problematic
      in newborns due to decreased sensitivity and specificity; more research is needed
      regarding best practice in diagnosis. Established protocols are needed to address
      the healthcare of TB-exposed providers in the NICU.

PMID- 30096059
TI  - Effectiveness of probiotics in the management of inflammatory arthritis: a
      systematic review protocol.
AB  - REVIEW QUESTIONS: The questions of this systematic review are: i) What is the
      effectiveness of probiotics as a therapeutic intervention for individuals living
      with inflammatory arthritis? ii) What are the reported adverse effects of
      probiotics when used as a therapeutic intervention for individuals living with
      inflammatory arthritis?

PMID- 30096060
TI  - Osteoporotic Fracture Risk and Health Care Burden in Patients With Cirrhosis.
AB  - BACKGROUND AND AIMS: Risk factors for osteoporotic fracture as well as inpatient
      utilization and mortality have not been thoroughly studied in patients with
      cirrhosis. We analyzed data from a national database to determine fracture risk
      in patients with cirrhosis, specific risk factors, and the effect of fractures on
      health care utilization. METHODS: We performed an observational study using
      serial cross-sectional data to examine fracture-related hospitalizations of
      patients with cirrhosis using the National Inpatient Sample from 2012 to 2013. We
      collected data on fracture-related hospitalizations and utilization in the form
      of length of stay (LOS), total hospital costs, and inpatient mortality. We used
      multivariate regression to determine risk factors for fracture and fracture
      related mortality. RESULTS: Patients with cirrhosis and an osteoporotic fracture
      had a mean LOS of 10.4 days and incurred $26,582 per hospitalization, which were
      statistically different from noncirrhotic patients with fracture (LOS: 6.60 d,
      cost: $17,918) and cirrhotic patients without fracture (LOS: 7.84 d, $18,912).
      Malnutrition was associated with increased odds of fracture [odds ratio (OR),
      1.29; 95% confidence interval (CI), 1.20-1.39] and inpatient mortality (OR, 1.40;
      95% CI, 1.12-1.76). Obesity was protective against both fracture (OR, 0.78; 95%
      CI, 0.71-0.85) and fracture-related mortality (OR, 0.82; 95% CI, 0.59-1.14).
      CONCLUSIONS: Hospitalizations for osteoporotic fractures in patients with
      cirrhosis are a significant source of health care burden and mortality. More
      attention should be paid to screening patients with cirrhosis for low bone mass.
      Malnutrition is associated with increased fracture risk and fracture-related
      mortality, representing a modifiable risk factor worthy of addressing in patients
      with cirrhosis.

PMID- 30096061
TI  - Narrow Band Imaging for Surveillance in Inflammatory Bowel Disease: A Systematic
      Review and Meta-Analysis.
AB  - BACKGROUND: The role of narrow band imaging (NBI) for surveillance colonoscopy in
      patients with inflammatory bowel disease (IBD) is debatable. We aim to compare
      NBI versus other endoscopic techniques in surveillance of IBD basing on current
      evidences. METHODS: A systematic search of PubMed, Embase, and the Cochrane
      Library databases was conducted for relevant studies. To assess the detection
      efficacy, we estimated risk ratios (RRs) for dichotomous outcomes and mean
      differences (MDs) for continuous outcomes. To assess the differentiation
      efficacy, we estimated sensitivity and specificity of NBI with reference to
      histology. All outcome variables were pooled using a random-effects model.
      Heterogeneity was tested by the Q statistic and I statistic. RESULTS: A total of
      10 studies involving 938 participants were included. Statistically significant
      differences were not found in the likelihood of detecting patients with
      dysplastic lesions [RR, 1.11; 95% confidence interval (CI), 0.83-1.48] nor in the
      likelihood of detecting dysplastic lesions by targeted biopsies (RR, 0.76; 95%
      CI, 0.51-1.12) between NBI and other techniques, and there was also no difference
      in the likelihood of detecting dysplastic subtypes. NBI required shorter
      procedural time compared with other techniques (MD, -10.23; 95% CI, -11.53 to 
      8.92). The sensitivity and specificity of NBI to differentiate neoplastic lesions
      from non-neoplastic lesions were 0.64 (95% CI, 0.50-0.77) and 0.74 (95% CI, 0.69
      0.79), respectively, and the area under the curve (AUC) was 0.7626. CONCLUSIONS:
      Although a shorter procedural time is needed, the clinical application of NBI for
      both dysplasia detection and neoplasia differentiation in IBD is not superior to
      other endoscopic techniques.

PMID- 30096062
TI  - Music Appreciation of Adult Hearing Aid Users and the Impact of Different Levels
      of Hearing Loss.
AB  - OBJECTIVES: The main aim of this study was to collect information on music
      listening and music appreciation from postlingually deafened adults who use
      hearing aids (HAs). It also sought to investigate whether there were any
      differences in music ratings from HA users with different levels of hearing loss
      (HL; mild, versus moderate to moderately-severe, versus severe or worse. DESIGN:
      An existing published questionnaire developed for cochlear implant recipients was
      modified for this study. It had 51 questions divided into seven sections: (1)
      music listening and music background; (2) sound quality; (3) musical styles; (4)
      music preferences; (5) music recognition; (6) factors affecting music listening
      enjoyment; and (7) music training program. The questionnaire was posted out to
      adult HA users, who were subsequently divided into three groups: (i) HA users
      with a mild HL (Mild group); (ii) HA users with a moderate to moderately-severe
      HL (Moderate group); and (iii) HA users with a severe or worse (Severe group) HL.
      RESULTS: One hundred eleven questionnaires were completed; of these, 51
      participants had a mild HL, 42 had a moderate to moderately-severe loss, and 18 a
      severe or worse loss. Overall, there were some significant differences noted,
      predominantly between the Mild and Severe groups, with fewer differences between
      the Mild and Moderate groups. The respondents with the greater levels of HL
      reported a greater reduction in their music enjoyment as a result of their HL and
      that HAs made music sound significantly less melodic for them. It was also
      observed that the Severe group's mean scores for both the pleasant rating as well
      as the combined rating for the six different musical styles were lower than both
      the Mild and Moderate groups' ratings for every style, with just one exception
      (pop/rock pleasantness rating). There were significant differences between the
      three groups for the styles of music that were reported to sound the best with
      HA(s), as well as differences between the ratings on more specific timbre rating
      scales used to rate different elements of each style. In rating the pleasantness
      and naturalness of different musical instruments or instrumental groups, there
      was no difference between the groups. There were also significant differences
      between the Mild and Severe groups in relation to musical preferences for the
      pitch range of music, with the Severe group significantly preferring male singers
      and lower pitched instruments. CONCLUSIONS: The overall results indicated little
      difference in music appreciation between those with a mild versus moderate loss.
      However, poorer appreciation scores were given by those with a severe or worse
      HL. This would suggest that HAs or HL have a negative impact on music listening,
      particularly when the HL becomes more significant. There was a large degree of
      variability in ratings, though, with music listening being satisfactory for some
      listeners and largely unsatisfactory for others, in all three groups. Music
      listening preferences also varied significantly, and the reported benefit (or
      otherwise) provided by the HA for music was also mixed. The overriding
      variability in listening preferences and ratings leads to the question as to the
      benefit and effectiveness of generic, manufacturer-derived music programs on HAs.
      Despite the heterogeneity in the listening habits, preferences, and ratings, it
      is clear that music appreciation and enjoyment is still challenging for many HA
      users and that level of HL is one, but not the only factor that impacts on music
      appreciation.

PMID- 30096063
TI  - Interscanner and Intrascanner Comparison of Virtual Unenhanced Attenuation Values
      Derived From Twin Beam Dual-Energy and Dual-Source, Dual-Energy Computed
      Tomography.
AB  - OBJECTIVE: The aim of the current study was to evaluate the reliability and
      comparability of virtual unenhanced (VUE) attenuation values derived from scans
      of a single-source, dual-energy computed tomography using a split-filter (tbDECT)
      to a dual-source dual-energy CT (dsDECT). MATERIALS AND METHODS: In this
      retrospective study, comparisons for tbDECT and dsDECT were made within and
      between different dual-energy platforms. For the interscanner comparison, 126
      patients were scanned with both scanners within a time interval of 224 +/- 180
      days; for the intrascanner comparison, another 90 patients were scanned twice
      with the same scanner within a time interval of 136 +/- 140 days. Virtual
      unenhanced images were processed off of venous phase series. Attenuation values
      of 7 different tissues were recorded. Disagreement for VUE HU measurements
      greater than 10 HU between 2 scans was defined as inadequate. RESULTS: The
      interscanner analysis showed significant difference between tbDE and dsDE VUE CT
      values (P < 0.01) for 6 of 7 organs. Percentage of cases that had more than 10 HU
      difference between tbDE and dsDE for an individual patient ranged between 15%
      (left kidney) and 62% (spleen).The intrascanner analysis showed no significant
      difference between repeat scans for both tbDECT and dsDECT (P > 0.05). However,
      intrascanner disagreements for the VUE HU measurements greater than 10 HU were
      recorded in 10% of patients scanned on the tbDECT and 0% of patients scanned on
      the dsDECT. The organs with the highest portion of greater than 10 HU errors were
      the liver and the aorta (both 20%). CONCLUSIONS: Dual-energy techniques vary in
      reproducibility of VUE attenuation values. In the current study, tbDECT
      demonstrated higher variation in VUE HU measurements in comparison to a dsDECT.
      Virtual unenhanced HU measurements cannot be reliably compared on follow-up CT,
      if these 2 different dual-energy CT platforms are used.

PMID- 30096064
TI  - Pulmonary Function Impairment from Exposure to Mixed Organic Solvents in Male
      Shipyard Painters.
AB  - OBJECTIVES: This study aimed to examine the effects of chronic exposure to
      organic solvents on lung function in a shipyard painters. METHODS: Male workers
      in the shipyard painting department were selected as the organic solvents
      exposure group. Exposure was classified according to the type of work usually
      performed, and the cumulative exposure index was obtained using the results of
      biological monitoring. These were then used to divide the exposure group into low
      exposure and high-exposure groups, and the dose-response relationships were
      examined for decreased lung function. For ventilation indices, we obtained the
      forced vital capacity (FVC), forced expiratory volume in the first second (FEV1),
      the FEV1/FVC ratio, and the maximal mid-expiratory flow (MMF) from the forced
      expiratory flow-volume curve and also calculated these as percentages of the
      predicted values. RESULTS: FVC and FEV1 showed no significant differences among
      the control, and low-exposure and high-exposure groups, but FEV1 as a percentage
      of its predicted value (%FEV1) decreased with increasing exposure at 90.0%,
      90.9%, and 90.0% in the control, low-exposure, and high-exposure groups,
      respectively. MMF% predicted also decreased significantly at 98.5%, 90.1%, and
      88.4% in the control, low-exposure, and high-exposure group, respectively,
      indicating that workers exposed to organic solvents showed obstructive
      respiratory disease. CONCLUSIONS: Exposure to organic solvents is associated with
      obstructive pulmonary dysfunction rather than restrictive pulmonary dysfunction.

PMID- 30096065
TI  - Significant Decreasing Trend in Low Back Injuries in a Beverage Company.
AB  - BACKGROUND: Work-related injuries in the U.S. have steadily declined over the
      past three decades. OBJECTIVE: The aim of this study was to compare trends of the
      most frequently injured body parts from a beverage company over an 8-year study
      period (2008 to 2015). METHOD: Work-related injury claims with more than 3 days
      of missed work (N = 20,203) were classified into body part groups, including low
      back, knee, shoulder, and all other(s). Descriptive statistics and linear models
      were used to evaluate trends over time. RESULTS: The total number of injuries
      decreased from 6.57 per 100 to 3.79 per 100 employees from 2008 to 2015.
      Proportion of low back injuries decreased from 22.0% to 15.4% (P < 0.001) over
      the study period. Proportionally, knee(s), shoulder(s), and all other injuries
      increased, but the changes did not reach statistical significance. CONCLUSION:
      Low back injuries decreased at a faster rate than knee, shoulder, and all other
      injuries.

PMID- 30096066
TI  - Reliability of Common Provocative Tests for Shoulder Tendinitis.
AB  - OBJECTIVE: Accurate and reliable shoulder tendinopathy exam maneuvers are
      essential for diagnosing and treating shoulder pain; however, studies have
      reported varying results as to the accuracy of common maneuvers. Thus, data from
      a large, cross-sectional study were used to systematically quantify the
      reliability and accuracy of clinical diagnostic tests. METHODS: Baseline data
      from the WISTAH cohort study were used to evaluate inter-tester reliability and
      accuracy of common provocative shoulder exam tests compared to a case definition
      of shoulder tendinitis. RESULTS: Inter-tester reliability showed reliable
      consistency between providers with kappa coefficients between 89.5-94.8% for all
      tests. However, sensitivity was generally poor (3.0-60.6%). Specificity was
      consistently high (96.2-99.6%). CONCLUSIONS: Common shoulder provocative tests
      show low sensitivity but high specificity, which implies that the primary utility
      of examination maneuvers is for their negative predictive values.

PMID- 30096067
TI  - Modeling the implementation of population-level isoniazid preventive therapy for
      tuberculosis control in a high HIV-prevalence setting.
AB  - BACKGROUND: We model the epidemiological impact of providing isoniazid preventive
      therapy (IPT) to South African adolescents, among whom HIV prevalence is low,
      latent tuberculosis (TB) prevalence is high, and school-based programs may enable
      population-level coverage. METHODS: We simulate a dynamic compartmental model of
      age-structured HIV and TB coepidemics in South Africa. HIV dynamics are modeled
      by infection status, CD4 cell count, and antiretroviral therapy; TB dynamics are
      modeled by disease stage, diagnosis, treatment, and IPT status. We analyze the
      effects of continuous IPT coverage among adolescents from 5 (baseline) to 90%.
      RESULTS: Our model is calibrated to WHO and the Joint United Nations Programme on
      HIV/AIDS epidemiological estimates. In simulations, increasing IPT coverage to
      50% among adolescents reduced active TB incidence by 5-34%. Increasing coverage
      to 90% led to a 9-40% reduction in active TB incidence. Expanded IPT access
      causes TB incidence to decline in the general population of HIV-positive
      individuals, as well as in adult HIV-positive individuals. CONCLUSION: Targeting
      IPT to a secondary school population with high latent TB prevalence and low-HIV
      prevalence, in which risk of false-negative diagnosis of active TB is low and IPT
      benefits are more established, could have substantial benefits to adolescents and
      spillover benefits to the adult population.

PMID- 30096068
TI  - Transmission dynamics among participants initiating antiretroviral therapy upon
      diagnosis of early acute HIV-1 infection in Thailand.
AB  - OBJECTIVE: To assess transmission characteristics in a predominantly MSM cohort
      initiating antiretroviral therapy (ART) immediately following diagnosis of acute
      HIV-1infection (AHI). METHODS: A longitudinal study (2009-2017) was performed in
      participants with AHI (n = 439) attending a single clinic in Bangkok. Plasma
      samples obtained prior to ART were used to obtain HIV-1 pol sequences and
      combined with clinical and epidemiologic data to assess transmission dynamics
      (cluster formation and size) using phylogenetic analysis. Clusters were estimated
      using maximum likelihood, genetic distance of 1.5% and visual inspection. The
      potential transmitter(s) in a cluster was determined using time to viral
      suppression and interview data. RESULTS: The cohort was predominantly MSM (93%)
      and infected with HIV-1 CRF01_AE (87%). Medians (ranges) for age and viral load
      prior to ART were 26 (18-70) years and 5.9 (2.5-8.2) log10 HIV-1 RNA copies/ml.
      Median time from history of HIV-1 exposure to diagnosis was 19 (3-61) days. Viral
      suppression was observed in 388 of 412 (94%) participants at a median time of 12
      weeks following ART. Twenty-six clusters with median cluster size of 2 (2-5)
      representing 62 of 439 (14%) participants were observed. Younger age was
      associated with cluster formation: median 28 versus 30 years for unique
      infections (P = 0.01). A potential transmitter was identified in 11 of 26 (42%)
      clusters. CONCLUSION: Despite high rates of viral suppression following diagnosis
      and treatment of AHI within a cohort of young Thai MSM, HIV-1 transmission
      continued, reflecting the need to expand awareness and treatment access to the
      entire MSM population.

PMID- 30096069
TI  - The association between oral disease and type of antiretroviral therapy among
      perinatally HIV-infected youth.
AB  - OBJECTIVES: This study explores the association between combination
      antiretroviral therapy (cART) and oral health outcomes (dental and periodontal)
      among perinatally HIV-infected (PHIV) youth. METHODS: We conducted a cross
      sectional study of oral health among PHIV youth participating in the Oral Health
      substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research
      sites were trained/calibrated on how to perform a standardized oral mucosal,
      dental and periodontal examination. They assessed the decayed-missing-filled
      surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and
      the number of teeth with gingival bleeding on probing for each participant were
      derived from the examination. Data for analysis included lifetime measurements of
      CD4 cell count and viral load, sociodemographic information and current/past
      history of ART. RESULTS: Among 209 PHIV youth, 95% were on ART at the time of
      enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found
      that the mean decayed teeth score of those receiving cART containing an integrase
      inhibitor was 86% higher than that of those on cART without an integrase
      inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load
      and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was
      associated with a significantly lower DMFT score than participants who initiated
      at age 6 years and older. CONCLUSION: Our study revealed that PHIV youth who
      received cART containing an integrase inhibitor had a significantly higher number
      of untreated active caries than those on cART without an integrase inhibitor.
      This may warrant closer dental surveillance of those receiving an integrase
      inhibitor.

PMID- 30096070
TI  - Drug resistance among patients who acquired HIV infection in a preexposure
      prophylaxis trial.
AB  - BACKGROUND: The IPERGAY ANRS trial showed that on-demand preexposure prophylaxis
      (PrEP) with tenofovir (TDF) and emtricitabine (FTC) was highly effective in
      preventing HIV infection among highly exposed MSM. Here, we analyzed drug
      resistance-associated mutations (RAMs) among all participants who acquired HIV
      infection during this trial. METHODS: Resistance was analyzed on frozen plasma at
      the time of HIV diagnosis among participants enrolled in the double-blind and
      open-label phases of the ANRS IPERGAY trial. Reverse transcriptase sequencing was
      performed, using population-based and ultradeep sequencing (454 GS Flex).
      Adherence was measured by pill counting and by plasma tenofovir and FTC assay.
      RESULTS: During the trial, 31 participants were diagnosed with HIV-1 infection
      (subtype B, 64.5%), using antigen/antibody immune assay in 29 cases and plasma
      HIV RNA assay in two. The median plasma HIV-1 RNA level was 5.52 log10 copies/ml.
      Drug resistance was tested in 12 participants before starting PrEP, in six
      assigned to TDF/FTC group and in 13 assigned to placebo group. Primary resistance
      to nucleoside reverse transcriptase inhibitors (zidovudine) and/or nonnucleoside
      reverse transcriptase inhibitors was detected in six participants (19%; 95%
      confidence interval 7-42). No major or minor TDF-resistant or FTC-resistant
      variants were detected. CONCLUSION: No TDF or FTC resistance-associated mutations
      were found among participants who acquired HIV in the ANRS IPERGAY trial.

PMID- 30096071
TI  - Immunogenicity and safety of yellow fever vaccine in HIV-1-infected patients.
AB  - OBJECTIVES: The objective of this study is to investigate immunogenicity and
      safety of the yellow fever vaccine (YFV) in HIV-infected (HIV+) patients with
      high CD4 T-cell counts. DESIGN: In this prospective, comparative study of YFV
      naive adults: 40 HIV+ under antiretroviral therapy (ART) with CD4 T-cell count
      above 350 cells/MUl and plasma HIV-RNA less than 50 copies/ml for at least 6
      months and 31 HIV-negative (HIV-) received one injection of the YF-17D strain
      vaccine. METHODS: Serologic response was assessed by using a plaque reduction
      neutralizing test and YFV-specific T cells by using an INFgamma-Elispot assay.
      RESULTS: YFV was well tolerated in both groups. Most participants had
      asymptomatic YFV viremia at day (D) 7 after vaccination (77% of HIV- and 82% of
      HIV+, P = 0.58), with higher plasma level of YFV RNA in HIV+ than in HIV- (median
      2.46 log10 copies/ml (range: 1.15-4.16) and 1.91 log10 copies/ml (1.15-3.19),
      respectively, P = 0.011). A significant but transient decrease in CD4 cell counts
      was seen at D7 in both groups, more pronounced in HIV- than in HIV+ patients (
      261.5 versus -111.5 cells/MUl, respectively, P = 0.0003), but no HIV breakthrough
      was observed in plasma. All participants developed protective neutralizing
      antibody levels from D28 and up to 1 year after injection. At D91, fewer HIV+
      than HIV- participants exhibited YFV T-cell response (20 versus 54%,
      respectively, P = 0.037). CONCLUSION: At 1 year, YFV was immunogenic and well
      tolerated in HIV-infected adults under ART with CD4 T-cell counts above 350
      cells/MUl. However, a lower immunity of YFV T cells in HIV-infected patients was
      observed as compared with HIV- participants. CLINICAL TRIALS REGISTRATION:
      NCT01426243.

PMID- 30096072
TI  - Aspartate aminotransferase-to-platelet ratio index increases significantly 3
      years prior to liver-related death in HIV-hepatitis-coinfected men.
AB  - : The utility of longitudinal AST-to-platelet ratio index (APRI), a surrogate for
      hepatic fibrosis, is unknown. We compared APRI up to 9 years before liver-related
      death among 57 cases of viral hepatitis-infected men (91% HIV+) to matched
      controls. APRI was stable among controls but, among cases, increased 4.6%/year
      from 9 to 3 years predeath (P = 0.10) and 30%/year during the 3 years predeath (P
      < 0.001). Thus, rapid APRI increase may predict impending liver-related death in
      HIV-viral hepatitis coinfection.

PMID- 30096073
TI  - Increasing prevalence of self-reported HIV preexposure prophylaxis use in
      published surveys: a systematic review and meta-analysis.
AB  - : When combining results from all published surveys, about one in nine global
      study participants (10.7%) reported ever using preexposure prophylaxis (PrEP) by
      2017, a significant increase since US FDA approval in 2012 [odds ratio (OR) =
      1.6/year, P < 0.00001]. Moreover, nearly one in six US-based study participants
      (17.3%) and nearly one in four MSM who met the Centers for Disease Control and
      Prevention's PrEP indications (24.5%) reported ever using PrEP by 2016. The odds
      of reporting PrEP use are approximately doubling each year (OR = 1.8/year, P <
      0.00001; OR = 2.0/year, P < 0.00001).

PMID- 30096074
TI  - Regression of liver fibrosis after curing chronic hepatitis C with oral
      antivirals in patients with and without HIV coinfection.
AB  - BACKGROUND: Treatment with direct-acting antivirals (DAA) eradicates hepatitis C
      virus (HCV) from most chronic carriers. Information on regression of liver
      fibrosis and the influence of HIV is scarce in cured patients. METHODS: All
      consecutive HCV-infected individuals treated with DAA at our institution were
      examined. Hepatic elastography was performed at baseline and at the time of
      SVR12. Liver fibrosis regression was defined as a shift from advanced fibrosis
      (Metavir F3-F4) to null-mild fibrosis (F0-F2) and/or a reduction greater than 30%
      kPa. AST to platelet ratio index (APRI) and fibrosis 4 (FIB-4) scores were
      calculated in parallel. RESULTS: A total of 260 patients were treated with DAA.
      All but 14 achieved SVR12 and represented the study population. HIV confection
      was present in 42%. At baseline, 57.2% had advanced liver fibrosis with a median
      of 11 kPa, FIB-4 of 2.4, and APRI of 0.95. At the time of SVR12, a median
      reduction of 2.1 kPa (P < 0.001) was recognized using elastography. A significant
      fibrosis regression was seen in 40%, being more frequent in patients with
      baseline advanced fibrosis than in those with null-mild fibrosis (52.3 vs. 22.5%;
      P < 0.001). Even so, 41.2% of patients with baseline F3-F4 kept within cirrhotic
      scores. In multivariable analysis, only baseline stiffness was significantly
      associated with the extent of liver fibrosis regression. CONCLUSION: HCV cure
      with DAA is associated with regression of liver fibrosis in most patients treated
      with DAA, as measured using elastography, FIB-4 and APRI. This benefit is more
      pronounced in patients with baseline advanced fibrosis and cirrhosis. The
      dynamics of liver fibrosis regression are not influenced by HIV coinfection.

PMID- 30096075
TI  - Estimating the number of people living with HIV and the undiagnosed fraction in
      Spain in 2013.
AB  - OBJECTIVE: We aim to estimate the number of people living with HIV and the
      undiagnosed fraction in Spain, where coverage of the HIV surveillance system has
      only recently become complete. METHODS: The reconstruction of all HIV diagnoses
      and infections was obtained by combining HIV and AIDS surveillance data. The
      imputation of the diagnoses and back-calculation of the infection incidence are
      integrated in a Bayesian framework to take into account the uncertainty
      associated with unavailable data. RESULTS: An estimated 141 000 [95% credible
      interval (CI) 128 000-155 000] persons were living with HIV by the end of 2013,
      in Spain and 18% (95% CI 14.3-22.1%) were unaware of it. A similar fraction of
      undiagnosed infections was obtained in men who have sex with men and
      heterosexuals (18.8 and 20.1%, respectively), but for injection drug users, this
      fraction was 3.5%. CONCLUSION: This study provides the first estimates of the
      number of people living with HIV and the undiagnosed fraction in Spain, using
      routine surveillance data. The proposed method could be useful for countries
      where the geographical coverage of the HIV surveillance system is partial or was
      completed only recently.

PMID- 30096076
TI  - Structural and functional characterization of HIV-1 cell fusion inhibitor T20.
AB  - OBJECTIVE: The peptide drug T20 (enfuvirtide), derived from the C-terminal heptad
      repeat region of HIV-1 gp41, is the only membrane fusion inhibitor available for
      treatment of viral infection; however, its mechanism of action remains elusive
      and its structural basis is lacking. DESIGN: We focused on determining the
      crystal structure of T20 in complex with N39, a target mimic peptide derived from
      the N-terminal heptad repeat region of gp41. On the basis of the structural
      information, the mechanisms of action of T20 and its resistance were further
      characterized. METHODS: A panel of peptides was synthesized. The T20/N39 complex
      was assembled for crystallization studies. Circular dichroism spectroscopy,
      isothermal titration calorimetry (ITC), native polyacrylamide gel electrophoresis
      (N-PAGE), and mutational analysis were applied to analyze the structural and
      functional properties. RESULTS: A crystal structure of six-helical bundle (6-HB)
      structure formed by T20 and N39 was determined with a resolution limit of 2.3 A,
      which revealed the critical intrahelical and interhelical interactions underlying
      the mechanism of action of T20 and its resistance mutations. Although the
      structural properties in the C-terminal tryptophan-rich motif (TRM) of T20 and
      the fusion peptide proximal region (FPPR) of N39 could not be finely defined by
      the structure, the data from biophysical and mutational analyses verified the
      essential roles of the TRM and FPPR motifs for the binding and inhibitory
      activities of T20. CONCLUSION: For the first time, our studies provide a
      structural basis of T20, which help our understanding on the mechanisms of HIV-1
      fusion and its inhibition.

PMID- 30096077
TI  - Topiramate Pharmacotherapy for Alcohol Use Disorder and Other Addictions: A
      Narrative Review.
AB  - : Topiramate is a non-benzodiazepine anticonvulsant medication with multi-faceted
      pharmacologic action. It has emerged as an efficacious pharmacotherapeutic option
      for the treatment of addiction, especially alcohol use disorder (AUD). We present
      a broad narrative review of the putative mechanism of action and clinical utility
      of topiramate with regard to AUD and other substance use disorders. Collective
      evidence suggests topiramate is an effective treatment option in AUD, with
      notable efficacy in reducing harmful drinking patterns in AUD. Though not
      currently approved by the United States Food and Drug Administration for the
      indication of AUD, topiramate should be considered as a pharmacological treatment
      option with high utility among AUD patients. Early pharmacogenetic studies raise
      the intriguing possibility of identifying patients likely to respond to
      topiramate using genetic testing, and initial studies show that topiramate may
      also be useful in treating cocaine use disorder, smoking cessation and behavioral
      addictions. However, further research is needed in all these areas.

PMID- 30096078
TI  - Topiramate Treatment of Alcohol Use Disorder in Clinical Practice.
AB  - : Topiramate is an anticonvulsant medication with increasingly strong evidence,
      supporting its use for treating alcohol use disorder (AUD) based on clinical
      trials. These clinical cases summarize the initiation and titration of topiramate
      in AUD treatment. The core issues of patient selection, consideration of comorbid
      psychiatric and medical conditions, side-effect profile, safety and effectiveness
      are reviewed. Addiction physicians should take a leading role in using topiramate
      to treat AUDs, working with patients to balance the benefits of topiramate with
      the risk.

PMID- 30096079
TI  - Smoothing Effect in Vital Sign Recordings: Fact or Fiction? A Retrospective
      Cohort Analysis of Manual and Continuous Vital Sign Measurements to Assess Data
      Smoothing in Postoperative Care.
AB  - BACKGROUND: Data smoothing of vital signs has been reported in the anesthesia
      literature, suggesting that clinical staff are biased toward measurements of
      normal physiology. However, these findings may be partially explained by
      clinicians interpolating spurious values from noisy signals and by the
      undersampling of physiological changes by infrequent manual observations. We
      explored the phenomenon of data smoothing using a method robust to these effects
      in a large postoperative dataset including respiratory rate, heart rate, and
      oxygen saturation (SpO2). We also assessed whether the presence of the vital sign
      taker creates an arousal effect. METHODS: Study data came from a UK upper
      gastrointestinal postoperative ward (May 2009 to December 2013). We compared
      manually recorded vital sign data with contemporaneous continuous data recorded
      from monitoring equipment. We proposed that data smoothing increases differences
      between vital sign sources as vital sign abnormality increases. The primary
      assessment method was a mixed-effects model relating continuous-manual
      differences to vital sign values, adjusting for repeated measurements. We tested
      the regression slope significance and predicted the continuous-manual difference
      at clinically important vital sign values. We calculated limits of agreement
      (LoA) between vital sign sources using the Bland-Altman method, adjusting for
      repeated measures. Similarly, we assessed whether the vital sign taker affected
      vital signs, comparing continuous data before and during manual recording.
      RESULTS: From 407 study patients, 271 had contemporaneous continuous and manual
      recordings, allowing 3740 respiratory rate, 3844 heart rate, and 3896 SpO2 paired
      measurements for analysis. For the model relating continuous-manual differences
      to continuous-manual average vital sign values, the regression slope (95%
      confidence interval) was 0.04 (-0.01 to 0.10; P = .11) for respiratory rate, 0.04
      (-0.01 to 0.09; P = .11) for heart rate, and 0.10 (0.07-0.14; P < .001) for SpO2.
      For SpO2 measurements of 91%, the model predicted a continuous-manual difference
      (95% confidence interval) of -0.88% (-1.17% to -0.60%). The bias (LoA) between
      measurement sources was -0.74 (-7.80 to 6.32) breaths/min for respiratory rate, 
      1.13 (-17.4 to 15.1) beats/min for heart rate, and -0.25% (-3.35% to 2.84%) for
      SpO2. The bias (LoA) between continuous data before and during manual observation
      was -0.57 (-5.63 to 4.48) breaths/min for respiratory rate, -0.71 (-10.2 to 8.73)
      beats/min for heart rate, and -0.07% (-2.67% to 2.54%) for SpO2. CONCLUSIONS: We
      found no evidence of data smoothing for heart rate and respiratory rate
      measurements. Although an effect exists for SpO2 measurements, it was not
      clinically significant. The wide LoAs between continuous and manually recorded
      vital signs would commonly result in different early warning scores, impacting
      clinical care. There was no evidence of an arousal effect caused by the vital
      sign taker.

PMID- 30096082
TI  - Status of Women in Academic Anesthesiology: A 10-Year Update.
AB  - BACKGROUND: Gender inequity is still prevalent in today's medical workforce.
      Previous studies have investigated the status of women in academic
      anesthesiology. The objective of this study is to provide a current update on the
      status of women in academic anesthesiology. We hypothesized that while the number
      of women in academic anesthesiology has increased in the past 10 years, major
      gender disparities continue to persist, most notably in leadership roles.
      METHODS: Medical student, resident, and faculty data were obtained from the
      Association of American Medical Colleges. The number of women in anesthesiology
      at the resident and faculty level, the distribution of faculty academic rank, and
      the number of women chairpersons were compared across the period from 2006 to
      2016. The gender distribution of major anesthesiology journal editorial boards
      and data on anesthesiology research grant awards, among other leadership roles,
      were collected from websites and compared to data from 2005 and 2006. RESULTS:
      The number (%) of women anesthesiology residents/faculty has increased from 1570
      (32%)/1783 (29%) in 2006 to 2145 (35%)/2945 (36%) in 2016 (P = .004 and P < .001,
      respectively). Since 2006, the odds that an anesthesiology faculty member was a
      woman increased approximately 2% per year, with an estimated odds ratio of 1.02
      (95% confidence interval, 1.014-1.025; P < .001). In 2015, the percentage of
      women anesthesiology full professors (7.4%) was less than men full professors
      (17.3%) (difference, -9.9%; 95% confidence interval of the difference, -8.5% to 
      11.3%; P < .001). The percentage of women anesthesiology department chairs
      remained unchanged from 2006 to 2016 (12.7% vs 14.0%) (P = .75). To date, neither
      Anesthesia & Analgesia nor Anesthesiology has had a woman Editor-in-Chief. The
      percentage of major research grant awards to women has increased significantly
      from 21.1% in 1997-2007 to 31.5% in 2007-2016 (P = .02). CONCLUSIONS: Gender
      disparities continue to exist at the upper levels of leadership in academic
      anesthesiology, most importantly in the roles of full professor, department
      chair, and journal editors. However, there are some indications that women may be
      on the path to leadership parity, most notably, the growth of women in
      anesthesiology residencies and faculty positions and increases in major research
      grants awarded to women.

PMID- 30096080
TI  - Comparison of a Novel Cadaver Model (Fix for Life) With the Formalin-Fixed
      Cadaver and Manikin Model for Suitability and Realism in Airway Management
      Training.
AB  - BACKGROUND: Manikins are widely used in airway management training; however,
      simulation of realism and interpatient variability remains a challenge. We
      investigated whether cadavers embalmed with the novel Fix for Life (F4L)
      embalmment method are a suitable and realistic model for teaching 3 basic airway
      skills: facemask ventilation, tracheal intubation, and laryngeal mask insertion
      compared to a manikin (SimMan 3G) and formalin-fixed cadavers. METHODS: Thirty
      anesthesiologists and experienced residents ("operators") were instructed to
      perform the 3 airway techniques in 10 F4L, 10 formalin-fixed cadavers, and 1
      manikin. The order of the model type was randomized per operator. Primary
      outcomes were the operators' ranking of each model type as a teaching model
      (total rank), ranking of the model types per technique, and an operator's average
      verbal rating score for suitability and realism of learning the technique on the
      model. Secondary outcomes were the percentages of successfully performed
      procedures per technique and per model (success rates in completing the
      respective airway maneuvers). For each of the airway techniques, the Friedman
      analysis of variance was used to compare the 3 models on mean operator ranking
      and mean verbal rating scores. RESULTS: Twenty-seven of 30 operators (90%)
      performed all airway techniques on all of the available models, whereas 3
      operators performed the majority but not all of the airway maneuvers on all
      models for logistical reasons. The total number of attempts for each technique
      was 30 on the manikin, 292 in the F4L, and 282 on the formalin-fixed cadavers.
      The operators' median total ranking of each model type as a teaching model was 1
      for F4L, 2 for the manikin and, 3 for the formalin-fixed cadavers (P < .001). F4L
      was considered the best model for mask ventilation (P = .029) and had a higher
      mean verbal rating score for realism in laryngeal mask airway insertion (P =
      .043). The F4L and manikin did not differ significantly in other scores for
      suitability and realism. The formalin-fixed cadaver was ranked last and received
      lowest scores in all procedures (all P < .001). Success rates of the procedures
      were highest in the manikin. CONCLUSIONS: F4L cadavers were ranked highest for
      mask ventilation and were considered the most realistic model for training
      laryngeal mask insertion. Formalin-fixed cadavers are inappropriate for airway
      management training.

PMID- 30096081
TI  - Continuous Popliteal-Sciatic Blocks for Postoperative Analgesia: Traditional
      Proximal Catheter Insertion Superficial to the Paraneural Sheath Versus a New
      Distal Insertion Site Deep to the Paraneural Sheath.
AB  - We tested the hypothesis that during a continuous popliteal-sciatic nerve block,
      postoperative analgesia is improved with the catheter insertion point "deep" to
      the paraneural sheath immediately distal to the bifurcation between the tibial
      and common peroneal branches, compared with the traditional approach
      "superficial" to the paraneural sheath proximal to the bifurcation. The needle
      tip location was determined to be accurately located with a fluid bolus
      visualized with ultrasound; however, catheters were subsequently inserted without
      a similar fluid injection and visualization protocol (visualized air injection
      was permitted and usually implemented, but not required per protocol). The
      average pain (0-10 scale) the morning after surgery for subjects with a catheter
      inserted at the proximal subparaneural location (n = 31) was a median
      (interquartile) of 1.5 (0.0-3.5) vs 1.5 (0.0-4.0) for subjects with a catheter
      inserted at the distal supraparaneural location (n = 32; P = .927). Secondary
      outcomes were similarly negative.

PMID- 30096084
TI  - Narrative Review of Decision-Making Processes in Critical Care.
AB  - Several theories describing the decision-making process in the intensive care
      unit (ICU) have been formulated. However, none of them appreciate the
      complexities of the process in an eclectic way by unifying several miscellaneous
      variables in 1 comprehensive theory. The purpose of this review is to highlight
      the key intricacies associated with the decision-making process in the ICU, to
      describe the theoretical frameworks with a special emphasis on gaps of knowledge,
      and to offer some avenues for improvement. The application of theoretical
      framework helps us to understand and to modify the structure of the process.
      Expected utility theory, regret theory, prospect theory, fuzzy-trace theory,
      construal level theory, and quantum probability theory were formulated over the
      years to appreciate an increased complexity of the decision-making process in the
      ICU. However the decision makers engage, these models may affect patient care
      because each of these frameworks has several benefits and downsides. There are
      gaps of knowledge in understanding how physicians match the different theoretical
      frameworks of the decision-making process with the potentially high ICU
      variability and load, especially when the "best outcome" is often nondiscrete and
      multidimensional. Furthermore, it is unclear when the preferential application of
      reflexive, habitual, variable, and biased-prone processes results in patient and
      staff detriment. We suggest better matching of theoretical frameworks with
      strengths of the human decision-making process and balanced application computer
      aids, artificial intelligence, and organizational modifications. The key
      component of this integration is work to increase the self-awareness of decision
      making processes among residents, fellows, and attending physicians.

PMID- 30096083
TI  - Diagnostic Testing and Decision-Making: Beauty Is Not Just in the Eye of the
      Beholder.
AB  - To use a diagnostic test effectively and consistently in their practice,
      clinicians need to know how well the test distinguishes between those patients
      who have the suspected acute or chronic disease and those patients who do not.
      Clinicians are equally interested and usually more concerned whether, based on
      the results of a screening test, a given patient actually: (1) does or does not
      have the suspected disease; or (2) will or will not subsequently experience the
      adverse event or outcome. Medical tests that are performed to screen for a risk
      factor, diagnose a disease, or to estimate a patient's prognosis are frequently a
      key component of a clinical research study. Like therapeutic interventions,
      medical tests require proper analysis and demonstrated efficacy before being
      incorporated into routine clinical practice. This basic statistical tutorial,
      thus, discusses the fundamental concepts and techniques related to diagnostic
      testing and medical decision-making, including sensitivity and specificity,
      positive predictive value and negative predictive value, positive and negative
      likelihood ratio, receiver operating characteristic curve, diagnostic accuracy,
      choosing a best cut-point for a continuous variable biomarker, comparing methods
      on diagnostic accuracy, and design of a diagnostic accuracy study.

PMID- 30096085
TI  - What will be the future of pediatric ophthalmology?

PMID- 30096086
TI  - Nonsurgical treatment of diplopia.
AB  - PURPOSE OF REVIEW: As the population ages, the number of patients presenting to
      ophthalmologists with complaints of double vision is increasing. RECENT FINDINGS:
      Diplopia is known to occur for optical, neuroophthalmological, strabismological
      and even iatrogenic reasons following various ophthalmic surgical procedures. The
      mainstays of the nonsurgical treatment of diplopia including no treatment,
      partial or total occlusion, press-on or ground in prisms and vergence exercises
      (to increase fusional vergence amplitudes) have been utilized for some time.
      Although a review of the literature demonstrates that very little has been
      published on this topic in recent years, subtle treatment variations have
      evolved. SUMMARY: The ability to successfully manage patients' diplopia symptoms
      remains important to decrease the risk of patient injuries, as well as maximize
      their independence and quality of life. These concerns are especially important
      as patients age.

PMID- 30096087
TI  - New classification system for pediatric glaucoma: implications for clinical care
      and a research registry.
AB  - PURPOSE OF REVIEW: The Childhood Glaucoma Research Network (CGRN) has created a
      new classification system for childhood glaucoma that has become the first
      International Consensus Classification. The purpose of this review is to present
      this classification system and share its use to date. RECENT FINDINGS: The
      diagnoses of the classification system include glaucoma and glaucoma suspect. The
      primary glaucomas include: primary congenital glaucoma and juvenile open-angle
      glaucoma. The secondary glaucomas include: glaucoma following cataract surgery,
      glaucoma associated with nonacquired systemic disease or syndrome, glaucoma
      associated with nonacquired ocular anomalies, and glaucoma associated with
      acquired conditions. This system reached consensus agreement at the Ninth World
      Glaucoma Association Consensus, which has been adopted by the American Board of
      Ophthalmology, and has been implemented in outcomes research, incidence studies,
      and review articles. The new Robison D. Harley, MD CGRN International Pediatric
      Glaucoma Registry uses this classification system as a shared language, allowing
      international clinicians and researchers to collaborate and make large-scale
      investigations of this otherwise rare disease possible. SUMMARY: The diagnoses in
      this system are assigned by following a logical and systematically approachable
      path. The ability to easily adopt and implement the system lends itself to
      international research.

PMID- 30096088
TI  - Current management of childhood ptosis.
AB  - PURPOSE OF REVIEW: Blepharoptosis is a common problem encountered in the
      pediatric ophthalmology clinic. The presentation is obvious to both parents and
      referring physicians and often prompts urgent consultation. The current
      classification and management of childhood ptosis will be reviewed. RECENT
      FINDINGS: Recent refinements in techniques utilizing new materials hold promise
      for better, more predictable outcomes and improved long-term results. Autogenous
      tensor tendon fascia lata harvested from the patient's thigh remains the gold
      standard for many ptosis surgeons in frontalis suspension; however, other
      materials are commonly utilized, including silicone rod, Gore-Tex (ePTFE; W.L.
      Gore & Associates, Flagstaff, Arizona, USA), Mersilene polyester fiber mesh and
      Ethibond braided polyester (Ethicon US LLC, Somerville, New Jersey, USA),
      Supramid monofilament nylon (S. Jackson, Inc, Alexandria, Virginia, USA),
      prolene, and banked fascia lata. Other techniques include levator resection,
      posterior approach levatorpexy, and Muller's muscle conjunctival resection both
      with and without superior tarsectomy. Recent studies suggest that ptosis repair
      can be effectively combined with strabismus surgery. SUMMARY: The management of
      ptosis in infants and children demands a structured and disciplined approach to
      avoid the development of amblyopia and long-term visual compromise. Underlying
      systemic problems must be identified and surgical planning discussed in a timely
      fashion with caregivers. Recent studies help to further define the proper timing
      of surgical intervention and the optimal techniques to provide the best long-term
      results for these patients.

PMID- 30096089
TI  - Pediatric optic neuritis.
AB  - PURPOSE OF REVIEW: Pediatric optic neuritis may be challenging to diagnose and
      treat. Significant clinical investigation of optic neuritis occurring in adults
      guides current clinical practices. Differences in presentation and prognosis
      exist for pediatric patients with optic neuritis when compared with adults
      including the risk of developing multiple sclerosis. The aim of this review is to
      provide an update on latest advances in the diagnosis, treatment and current
      research concerning pediatric optic neuritis. RECENT FINDINGS: Limited case
      series and retrospective reviews constitute much of the data we know about
      patients with pediatric optic neuritis. Pediatric optic neuritis is included in
      the spectrum of neuroinflammatory diseases. Testing modalities (ocular coherence
      tomography and visual evoked potentials) and serologic testing (antibodies
      against aquaporin-4 and myelin oligodendrocyte glycoprotein) are being
      investigated for diagnostic and prognostic value. The low incidence of pediatric
      optic neuritis results in small sample sizes may contribute to conflicting
      results of different studies. SUMMARY: Recent advances in diagnostic and
      serologic testing in pediatric neuritis may offer better diagnosis, treatment and
      prediction of prognosis. Validation requires well designed prospective research.

PMID- 30096090
TI  - Sofosbuvir based regimens in the treatment of chronic hepatitis C genotype 1
      infection in African-American patients: a community-based retrospective cohort
      study.
AB  - BACKGROUND: Direct-acting antiviral (DAA) drugs have been highly effective in the
      treatment of chronic hepatitis C (HCV) infection. Limited data exist comparing
      the safety, tolerability, and efficacy of DAAs in African-American (AA) patients
      with chronic hepatitis C genotype 1 (HCV GT-1) in the community practice setting.
      We aim to evaluate treatment response of DAAs in these patients. PATIENTS AND
      METHODS: All the HCV GT-1 patients treated with DAAs between January 2014 and
      January 2018 in a community clinic setting were retrospectively analyzed.
      Pretreatment baseline patient characteristics, treatment efficacy with a
      sustained virologic response at 12 weeks post-treatment (SVR12), and adverse
      reactions were assessed. RESULTS: Two-hundred seventy-eight patients of AA
      descent were included in the study. One-hundred sixty-two patients were treated
      with ledipasvir/sofosbuvir (SOF)+/-ribavirin, 38 were treated with
      simeprevir/SOF+/-ribavirin, and 38 patients were treated with SOF/velpatasvir.
      Overall, SVR at 12 weeks was achieved in 94.6% in patients who received one of
      the three DAA regimens (93.8% in ledipasvir/SOF group, 92.1% in simeprevir/SOF
      group, and 97.4% in SOF/velpatasvir group). Previous treatment experience, HCV
      RNA levels and HIV status had no statistical significance on overall SVR
      achievement (P=0.905, 0.680, and 0.425, respectively). Compensated cirrhosis in
      each of the treatment groups did not influence overall SVR of 12. The most common
      adverse effect was fatigue (27%). None of the patients discontinued the treatment
      because of adverse events. CONCLUSION: In the real-world setting, DAAs are safe,
      effective, and well tolerated in African-American patients with chronic HCV GT-1
      infection with a high overall SVR rate of 94.6%. Treatment rates did not differ
      on the basis of previous treatment and compensated cirrhosis status.

PMID- 30096091
TI  - High sustained virologic response rate using generic directly acting antivirals
      in the treatment of chronic hepatitis C virus Egyptian patients: single-center
      experience.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major health problem in Egypt, with a
      high prevalence of genotype 4. AIM: This study aimed to evaluate the safety and
      efficacy of generic sofosbuvir (SOF) plus generic daclatasvir (DAC) with or
      without ribavirin in the treatment of Egyptian chronic HCV patients compared with
      the use of brand drugs. MATERIALS AND METHODS: An observational study that
      included 234 Egyptian chronic HCV patients was carried out. Patients were
      classified into two groups: group A (101 patients) received brand SOF 400 mg plus
      brand DAC 60 mg and group B (134 patients) received generic SOF 400 mg plus
      generic DAC 60 mg with or without ribavirin for 12 weeks. The end point was a
      sustained virological response at 12 weeks after treatment. RESULTS: Thirty-eight
      (37.2%) patients in group A were treatment experienced compared with 12 (9.02%)
      patients in group B; there were 39 (38%) cirrhotic patients in group A and 22
      (16.5%) cirrhotic patients in group B. In group A, 50% of patients received
      ribavirin, while in group B, 42.1% of patients received ribavirin. All patients
      were followed up; all of them attended their week 12 post-treatment visit with
      negative HCV RNA, with achievement of sustained virological response at 12 in
      100% of patients receiving generic drugs (group B) and 99% of patients receiving
      brand drugs (group A). Generic SOF and DAC were well tolerated, with mild adverse
      events including fatigue and headache. CONCLUSION: Use of generic SOF and DAC
      with or without ribavirin is an extremely effective and a well-tolerated
      treatment for Egyptian chronic HCV patients.

PMID- 30096092
TI  - Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single
      shot.
AB  - BACKGROUND/AIMS: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may
      include increased insulin resistance, upregulation of proinflammatory cytokines,
      lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that
      might act against a broad spectrum of gut bacteria. This study aimed to
      investigate the effects of rifaximin on NAFLD. PATIENTS AND METHODS: Fifty
      participants with biopsy-proven nonalcoholic steatohepatitis (NASH) were
      registered in this multicentric, double-blind, randomized, placebo-controlled
      study. BMI, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl
      transferase, lipid profile, serum endotoxin, homeostatic model assessment, toll
      like receptor-4, interleukin-10 (IL-10), IL-6, tumor necrosis factor-alpha, and
      cytokeratin-18 (CK-18) levels were evaluated at baseline and at 1, 3, and 6
      months of rifaximin therapy (1100 mg/day). RESULTS: Patients were randomized into
      two groups (rifaximin group; n=25 and placebo group; n=25). After 6 months of
      rifaximin therapy, patients with NASH showed a significant reduction in
      homeostatic model assessment, alanine aminotransferase, aspartate
      aminotransferase, gamma-glutamyl transferase, endotoxin, toll-like receptor-4, IL
      6, tumor necrosis factor-alpha, CK-18, and NAFLD-liver fat score (all P<0.05),
      but no changes in the lipid profile; moreover, there was a mild nonstatistically
      significant reduction of BMI. However, in the placebo group, there was no
      significant difference in these variables at baseline and after therapy.
      CONCLUSION: Rifaximin therapy appears to be effective and safe in modifying NASH
      through reduction of serum endotoxin and improvement of insulin resistance,
      proinflammatory cytokines, CK-18, and NAFLD-liver fat score.

PMID- 30096093
TI  - Development of a Nursing Electronic Medical Record Usability Protocol.
AB  - Assessing usability of an electronic medical record is useful for organizations
      wishing to customize their electronic medical record and determine the impact on
      usability. The purpose of this article is to describe the development of a
      protocol to measure electronic medical record usability from a nursing
      perspective and to develop a scoring methodology. The Technical Evaluation,
      Testing, and Validation of the Usability of Electronic Health Records (NISTIR
      7804), published by the National Institute of Standards and Technology, guided
      protocol development. Usability was determined by measuring effectiveness,
      efficiency, and satisfaction. Satisfaction was measured by the System Usability
      Scale, while effectiveness and efficiency were measured via performance testing
      by participants, who completed one of three scenarios. A protocol and scoring
      formula were developed and used to assess nursing usability, resulting in an
      overall "C" grade for the electronic medical record. Protocol implementation and
      the scoring/grading calculations can be replicated to assess electronic medical
      record usability. The three scenarios used in this protocol will be made
      available upon request from the primary author to promote the use of electronic
      medical record usability assessment. Using and expanding upon the government's
      recommended usability assessment guidelines, we were successful in measuring
      nursing electronic medical record usability and rating an electronic medical
      record.

PMID- 30096094
TI  - New perspectives in the therapeutic approach of peripheral T-cell lymphoma.
AB  - PURPOSE OF REVIEW: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of
      mature T-cell and natural killer (NK)-cell neoplasms in the WHO 2016
      classification. Patient prognosis is poor when treated with CHOP, and there is an
      unmet need for new drugs. Several agents have been developed for PTCL, and their
      use is the subject of this review. RECENT FINDINGS: Phase 2 studies demonstrated
      the activity of new drugs in Relapsed/refractory PTCL. Only four compounds were
      approved by the food and drug administration: romidepsin and belinostat, which
      are epigenetic modifiers, the antifolate agent pralatrexate, the immuno-conjugate
      brentuximab vedotin. New combinations have been tested, but the results were
      disappointing. Given the latest progress in biology, targeted agents are
      evaluated in different subtypes of PTCL. Relapsed anaplastic large-cell lymphoma
      exhibits improved prognosis with the approved anti-CD30 drug conjugate
      brentuximab vedotin. Localized nasal NK/T is treated with radiotherapy and
      nonanthracycline chemotherapy with L-asparaginase. Recently, immune checkpoint
      inhibitors demonstrated activity in NK/T lymphoma and can be used in elderly
      patients. SUMMARY: Treatment remains a challenge for PTCL, and several targeted
      drugs provide new approaches. Progress will be made incrementally in the
      different subtypes. One of the critical situations facing new drugs is the
      ability to run robust clinical trials in rare diseases.

PMID- 30096095
TI  - New insights into breast implant-associated anaplastic large cell lymphoma.
AB  - PURPOSE OF REVIEW: Breast implant-associated anaplastic large cell lymphoma (BI
      ALCL) is a rare form of lymphoma arising adjacent to a breast implant. We aim to
      review the pathogenesis and clinico-biological features of BI-ALCL. RECENT
      FINDINGS: BI-ALCL is a new provisional entity in the 2017 updated WHO
      classification. Among several hypotheses, BI-ALCL development seems to be
      determined by the interaction of immune response related to implant products and
      additional genetic events. SUMMARY: BI-ALCL is an uncommon T-cell lymphoma which
      is increasingly diagnosed since its first description in 1997 with 500 estimated
      cases worldwide. Two BI-ALCL subtypes correlating with clinical presentation have
      been described. Although most BI-ALCL patients with tumor cell proliferation
      restricted to the periprosthetic effusion and capsule have excellent outcomes,
      other patients presenting with a tumor mass, may have a more aggressive disease.
      The pathogenesis of BI-ALCL remains elusive. It is postulated that local chronic
      inflammation elicitated by bacterial infection or implant products may promote
      the activation and proliferation of T cells. Additional genetic events resulting
      in the activation JAK/STAT pathway are also incriminated. Further investigations
      are needed to better characterize the pathogenesis of this disease in order to
      determine the potential risk to develop BI-ALCL after surgical implants.

PMID- 30096096
TI  - The role of allogeneic stem cell transplantation in T-cell lymphoma.
AB  - PURPOSE OF REVIEW: T - and natural killer (NK) cell neoplasms are a heterogeneous
      group of rare diseases with often inferior outcome. Only few studies exist,
      clarifying the role of allogeneic transplantation in different clinical
      scenarios. Larger prospective randomized studies are largely missing even for the
      more frequent entities. Mostly retrospective analysis and anecdotal reports of
      patients with advanced disease are available, hampering direct conclusions on the
      significance of allogeneic stem cell transplantation (alloSCT). RECENT FINDINGS:
      Looking at recent data for T and NK cell neoplasm, it becomes evident that
      advances in donor search and availability of alternative stem cell sources as
      haploidentical or mismatched donors in addition to substantial improvements in
      graft-versus-host-disease prophylaxis reduce treatment-related mortality in
      alloSCT. The time point of transplantation has been described in a number of
      studies to be critically impacting outcome results as patients with advanced,
      chemorefractory disease often profit much less from alloSCT. SUMMARY: Allogeneic
      transplantation offers a treatment option that can induce long-term remissions
      even in the relapsed setting. Many patients do not reach transplantation though
      because of chemorefractory disease and efforts should be made to bring more
      patients to transplantation earlier in the course of disease.

PMID- 30096097
TI  - Tackling the challenges of brain metastases in solid tumors.

PMID- 30096098
TI  - Gingival Recession and Localized Aggressive Periodontitis Among HIV-Infected
      Children and Adolescents Receiving Antiretroviral Therapy.
AB  - BACKGROUND: Limited information is available on gingival recession or localised
      aggressive periodontitis among HIV-infected children and adolescents. This study
      reports on the prevalence of these conditions among children and adolescents
      receiving antiretroviral therapy (ART). METHODS: A cross-sectional study on HIV
      infected children and adolescents attending a Paediatric HIV clinic in Gauteng,
      South Africa, between January 2013 and June 2016. Patients received an oral
      examination and oral hygiene instructions, irrespective of oral- or dental
      related complaints. Hard and soft tissue pathology was managed and recorded,
      together with relevant demographic and clinical data. Statistical analysis was
      performed in Stata 14 with p <0.05 as significant. RESULTS: A total of 554
      children and adolescents aged 5 to 19 years (median age 12.2 years, IQR 10.3;
      14.9) were included, of whom 78 (14.1%) presented with gingival recession on
      permanent mandibular incisors and/or localised aggressive periodontitis of molar
      teeth. Multivariable logistic regression revealed that patients with gingival
      recession and aggressive periodontitis had a significantly shorter duration of
      ART, and were more likely to have suboptimal HIV-control (CD4 count <=500
      cells/uL and/or HIV viral load >=50 copies/mL) and be on advanced ART regimens
      after virological failure on 1- and 2-line treatment. CONCLUSION: The results
      emphasise the importance of oral health care among HIV-infected children and
      adolescents from the onset, in order to prevent and manage conditions that could
      result in tooth loss and permanent disfigurement. This is of particular
      importance in the presence of virological failure and immunosuppression.

PMID- 30096100
TI  - Case Fatality and Adverse Outcomes Are Reduced in Pregnant Women With Severe
      Sepsis or Septic Shock Compared With Age-Matched Comorbid-Matched Nonpregnant
      Women.
AB  - OBJECTIVES: Case fatality in pregnancy-associated severe sepsis or septic shock
      appears reduced compared with nonpregnant women with severe sepsis or septic
      shock. It remains unclear if this difference is due to pregnancy or better
      baseline health status, among others. Our study compared adverse outcomes of
      pregnancy-associated severe sepsis or septic shock with nonpregnant women with
      severe sepsis or septic shock while controlling for age and chronic
      comorbidities. DESIGN: Retrospective cohort study. SETTING: Nationwide Inpatient
      Sample, a stratified sample of 20% acute care hospital admissions in the United
      States. Each entry includes patient and hospital characteristics as well as
      International Classification of Diseases, 9th revision, Clinical Modification,
      diagnoses and procedures. SUBJECTS: Women of childbearing age (15-44 yr) with
      severe sepsis or septic shock-related hospitalizations during 1998-2012
      identified using International Classification of Diseases, 9th revision, Clinical
      Modification, codes. OUTCOMES: Case fatality, hospital length of stay, length of
      stay until death, number of organ failures, rates of mechanical ventilation, and
      hemodialysis were compared in women according to pregnancy status, controlling
      for age, and chronic comorbidities. MEASUREMENTS AND MAIN RESULTS: We identified
      5,968 pregnancy-associated severe sepsis or septic shock and 85,240 nonpregnant
      women with severe sepsis or septic shock hospitalizations. Crude case fatality of
      pregnancy-associated severe sepsis or septic shock (9.6%) was lower than
      nonpregnant women with severe sepsis or septic shock (16.8%). The rate ratio for
      case fatality adjusted for socioeconomic status and race was 0.57 (95% CI, 0.52
      0.62) while sequential adjustments for age and chronic comorbidities did not
      eliminate the association (rate ratio, 0.62 [95% CI, 0.57-0.68]) and 0.63 [95%
      CI, 0.57-0.68], respectively). Pregnancy-associated severe sepsis or septic shock
      was associated with shorter hospital length of stay (-0.83 d [95% CI, -1.32 to 
      0.34 d]), longer length of stay until death (2.61 d; [95% CI, 1.28-3.94 d]), and
      fewer organ failures (rate ratio, 0.95 [95% CI, 0.94-0.97]). CONCLUSIONS: Case
      fatality and adverse outcomes are reduced in women with pregnancy-associated
      severe sepsis or septic shock compared with nonpregnant women with severe sepsis
      or septic shock, and this is not explained by differences in age or chronic
      comorbidities alone. A less severe presentation of sepsis or protective effect of
      pregnancy may account for the difference observed with pregnancy-associated
      severe sepsis or septic shock.

PMID- 30096099
TI  - Increased Fibrinolysis as a Specific Marker of Poor Outcome After Cardiac Arrest.
AB  - OBJECTIVES: Recent data suggest that early increased fibrinolysis may be
      associated with unfavorable prognosis in cardiac arrest. The current study aimed
      to assess whether there is an optimal fibrinolysis cutoff value as determined by
      thrombelastometry at hospital admission to predict poor outcome in a cohort of
      adult patients with out-of-hospital cardiac arrest. DESIGN: Prospective
      observational cohort study. SETTING: Emergency department of a 2.100-bed tertiary
      care facility in Vienna, Austria, Europe. PATIENTS: Patients with out-of-hospital
      cardiac arrest of presumed cardiac origin, subjected to targeted temperature
      management, who had achieved return of spontaneous circulation at admission were
      analyzed. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fibrinolysis was
      assessed by thrombelastometry at the bedside immediately after hospital admission
      and is given as maximum lysis (%). The outcome measure was the optimal cutoff for
      maximum lysis at hospital admission to predict poor outcome (a composite of
      Cerebral Performance Category 3-5 or death) at day 30, assessed by receiver
      operating characteristic curve analysis. Seventy-eight patients (61% male, median
      59 yr) were included in the study from March 2014 to March 2017. Forty-two
      patients (54%) had a poor 30-day outcome including 23 nonsurvivors (30%). The
      maximum lysis cutoff at admission predicting poor 30-day outcome with 100%
      specificity (95% CI, 90-100%) was greater than or equal to 20%. Tissue-type
      plasminogen activator antigen levels were likewise elevated in patients with poor
      neurologic outcome or death 52 ng/mL (interquartile range, 26-79 ng/mL) versus 29
      ng/mL (interquartile range, 17-49 ng/mL; p = 0.036). CONCLUSIONS: Increased
      fibrinolysis at admission assessed by thrombelastometry specifically predicts
      poor outcome in cardiac arrest with presumed cardiac etiology.

PMID- 30096102
TI  - In the Next Issue.

PMID- 30096101
TI  - Laryngeal Injury and Upper Airway Symptoms After Oral Endotracheal Intubation
      With Mechanical Ventilation During Critical Care: A Systematic Review.
AB  - OBJECTIVES: To systematically review the symptoms and types of laryngeal injuries
      resulting from endotracheal intubation in mechanically ventilated patients in the
      ICU. DATA SOURCES: PubMed, Embase, CINAHL, and Cochrane Library from database
      inception to September 2017. STUDY SELECTION: Studies of adult patients who were
      endotracheally intubated with mechanical ventilation in the ICU and completed
      postextubation laryngeal examinations with either direct or indirect
      visualization. DATA EXTRACTION: Independent, double-data extraction and risk of
      bias assessment followed the Preferred Reporting Items for Systematic Reviews and
      Meta-Analyses guidelines. Risk of bias assessment followed the Cochrane
      Collaboration's criteria. DATA SYNTHESIS: Nine studies (seven cohorts, two cross
      sectional) representing 775 patients met eligibility criteria. The mean (SD; 95%
      CI) duration of intubation was 8.2 days (6.0 d; 7.7-8.7 d). A high prevalence
      (83%) of laryngeal injury was found. Many of these were mild injuries, although
      moderate to severe injuries occurred in 13-31% of patients across studies. The
      most frequently occurring clinical symptoms reported post extubation were
      dysphonia (76%), pain (76%), hoarseness (63%), and dysphagia (49%) across
      studies. CONCLUSIONS: Laryngeal injury from intubation is common in the ICU
      setting. Guidelines for laryngeal assessment and postextubation surveillance do
      not exist. A systematic approach to more robust investigations could increase
      knowledge of the association between particular injuries and corresponding
      functional impairments, improving understanding of both time course and prognosis
      for resolution of injury. Our findings identify targets for future research and
      highlight the long-known, but understudied, clinical outcomes from endotracheal
      intubation with mechanical ventilation in ICU.

PMID- 30096103
TI  - SPONTANEOUS CLOSURE OF MACULAR HOLE IN A PATIENT WITH MACULAR TELANGIECTASIA TYPE
      2.
AB  - PURPOSE: To present a case of macular hole associated with macular telangiectasia
      Type 2 (Mac-Tel 2) which underwent spontaneous closure. METHODS: A 58-year-old
      woman is admitted with complaints of blurred and distorted vision. Optical
      coherence tomography, fundus autofluorescence, and optical coherence tomography
      angiography were performed for diagnosis and follow-up. RESULTS: Optical
      coherence tomography revealed hyporeflective cavitations in both eyes, and full
      thickness macular hole covered with internal limiting membrane drape in the left
      eye. Fundus autofluorescence showed loss of hypoautofluorescence in temporal
      parafoveal area in the right eye, and centrally in the left one. Vascular
      irregularities were detected in optical coherence tomography angiography images.
      The patient was diagnosed as Mac-Tel 2. During the follow-up, the macular hole
      underwent a process of spontaneous closure, starting as bridging at the level of
      external limiting membrane and outer nuclear layer followed by further repairment
      and organization of the outer plexiform layer, accompanied with visual gain.
      CONCLUSION: Spontaneous closure of macular hole in patients with Mac-Tel 2 is a
      rare entity. We hypothesize that extension or proliferation of Muller cells,
      which leads to reconstruction of normal foveal structure, is the main mechanism
      for this phenomenon.

PMID- 30096104
TI  - Clinical Application of Cultured Stratified Epithelial Sheets Grown Under Feeder
      or Feeder-Free Conditions for Stable Vitiligo.
AB  - BACKGROUND: Autologous cultured therapy has emerged as an effective treatment for
      stable vitiligo. However, culture methods may include harmful agents and be
      unsuitable for therapeutic use in humans. OBJECTIVE: To investigate the safety
      and efficacy of autologous cultured epithelial sheets propagated under serum-free
      and feeder-free conditions for the treatment of stable vitiligo. METHODS: Twenty
      eight patients with stable vitiligo were included in this study. Keratinocytes
      and melanocytes from 14 patients were cultured under serum-free, feeder-free
      conditions (Group A). Epithelial cells from the remaining 14 patients were
      cultured according to Rheinward and Green's technique (Group B). Patients were
      followed up at 1, 3, 6, and 12 months after transplantation. RESULTS: The
      epithelial sheets cultured in Group A were thinner and more fragile than Group B,
      but there were no significant differences in repigmentation between the 2 groups.
      At 12-month follow-up, in Group A, repigmentation at graft sites was classified
      as excellent in 9 patients and good in 2 patients. In Group B, repigmentation was
      excellent in 8 patients and good in 4 patients. Scars at the donor sites were the
      most frequent adverse events associated with the procedure. CONCLUSION:
      Autologous epithelial sheet cultured in serum-free, feeder-free conditions is a
      safe and efficacious approach to cure stable vitiligo.

PMID- 30096105
TI  - Review of Common Alternative Herbal "Remedies" for Skin Cancer.
AB  - BACKGROUND: Alternative herbal remedies for skin cancer are commonly found on the
      Internet. Many websites contain inaccurate or false information regarding side
      effects and efficacy. OBJECTIVE: To review the evidence behind several commonly
      advertised herbal remedies that claim to cure skin cancer: black salve, eggplant,
      frankincense, cannabis, black raspberry, milk thistle, St. John's wort, and
      turmeric. METHODS: A PubMed search was performed using the common and scientific
      names of frequently advertised herbal remedies along with the terms "nonmelanoma
      skin cancer," or "basal cell carcinoma" or "squamous cell carcinoma," or
      "melanoma." RESULTS: Some preclinical studies have shown positive evidence that
      these substances can induce apoptosis in skin cancer, but clinical studies
      proving efficacy are either insufficient, nonexistent, or show negative evidence.
      Botanicals that were excluded are those that do not have published studies of
      their efficacy as skin cancer treatments. CONCLUSION: Online advertising may
      tempt patients to use botanical agents while citing efficacy found in preclinical
      studies. However, many agents lack strong clinical evidence of efficacy.
      Dermatologists must be aware of common herbal alternatives for skin cancer
      treatment to maintain effective patient communication and education.

PMID- 30096107
TI  - Efficacy of 1,550-nm Erbium-Glass Fractional Laser Treatment and Its Effect on
      the Expression of Insulin-Like Growth Factor 1 and Wnt/beta-Catenin in
      Androgenetic Alopecia.
AB  - BACKGROUND: A new treatment for androgenetic alopecia (AGA) is a 1,550-nm erbium
      glass (Er:Glass) fractional laser. The wound healing process associated with this
      treatment is believed to be due to the stimulation of hair regrowth. Both the
      Wingless-related integration site (Wnt) proteins and insulin-like growth factor 1
      (IGF-1) are important molecules that promote new hair growth. OBJECTIVE: The aim
      of this study was to evaluate the efficacy of 1,550-nm Er:Glass fractional laser
      treatment and determine the gene expression of IGF-1 and Wnt/beta-catenin in
      patients with AGA. METHODS: Twenty-three patients with AGA were enrolled. They
      received 12 treatments at 2-week intervals. A scalp biopsy was performed to
      evaluate mRNA levels of Wnt10A and IGF-1. Histopathologic samples were collected.
      RESULTS: Significant increases in hair count and shaft diameter that occurred
      from Month 4 until the end of the study were observed. Histological results
      showed increases in the follicular unit, anagen hair count, and the
      anagen:telogen ratio. No up-regulation of Wnt10A and IGF-1 mRNA was observed.
      CONCLUSION: The 1,550-nm Er:Glass fractional laser treatment can increase hair
      density and shaft diameter in patients with AGA. The mechanisms by which 1,550-nm
      Er:Glass laser treatment induces new hair growth may not be limited to
      Wnt10A/beta-catenin or IGF-1 expression.

PMID- 30096108
TI  - When.

PMID- 30096106
TI  - Phase 3 Study of OnabotulinumtoxinA Distributed Between Frontalis, Glabellar
      Complex, and Lateral Canthal Areas for Treatment of Upper Facial Lines.
AB  - BACKGROUND: Although commonly practiced, simultaneous onabotulinumtoxinA
      injections to multiple facial areas have not been investigated in prospective
      studies. OBJECTIVE: Evaluate safety and efficacy of onabotulinumtoxinA for
      treatment of forehead lines (FHL) distributed between the frontalis (20 U) and
      glabellar complex (20 U), with or without simultaneous lateral canthal areas
      (crow's feet lines [CFL], 24 U) treatment. METHODS: Subjects with moderate to
      severe FHL were randomized (2:2:1) to onabotulinumtoxinA 40 U, onabotulinumtoxinA
      64 U, or placebo. After 180 days, subjects could receive up to 2 additional open
      label onabotulinumtoxinA 64 U treatments. RESULTS: The intent-to-treat (ITT)
      population comprised 787 subjects, and the modified ITT (mITT) population
      (subjects with psychological impact) comprised 568. After 30 days,
      onabotulinumtoxinA 40 U and 64 U significantly improved investigator- and subject
      assessed FHL severity by at least 2 Facial Wrinkle Scale (FWS) grades in 45.6%
      and 53.0% of ITT subjects, respectively, versus 0.6% receiving placebo (both, p <
      .0001). Significantly more mITT subjects receiving onabotulinumtoxinA achieved
      investigator- and subject-assessed FWS ratings of none/mild versus placebo (p <
      .0001). OnabotulinumtoxinA was well tolerated. CONCLUSION: OnabotulinumtoxinA
      distributed between the frontalis and glabellar complex, with or without
      additional CFL injections, was safe and effective for treatment of moderate to
      severe FHL.

PMID- 30096109
TI  - Research Collaboration Among Doctorally Prepared Educators.

PMID- 30096110
TI  - Mitigating Barriers to Doctoral Education for Nurses.
AB  - AIM: This article reports preliminary outcomes of the Guiding Initiative for
      Doctoral Education, which promotes success in doctoral study. BACKGROUND: Nurses
      face challenges as they move intentionally, effectively, and expediently toward
      earning the doctorate. Selecting the doctoral education best suited to individual
      career goals is essential for success. METHOD: An intensive, daylong program
      focused on setting goals, generating personal action plans, and mobilizing
      resources to promote success in application and return to the role of student.
      RESULTS: Based on 70 nurses who participated in seven programs, 22 (31 percent)
      were admitted to their doctoral program of choice (6 PhD, 15 DNP, 1 EdD).
      CONCLUSION: Nurses benefit from and value learning about the options for doctoral
      study, requirements for educational opportunities, the nature of the commitment
      required, challenges commonly encountered during the process, and the impact
      advanced education can be expected to have on immediate and long-term career
      opportunities.

PMID- 30096112
TI  - Support Issues and Nursing Doctoral Students' Intent to Leave.
AB  - The purpose of this study was to explore, analyze, and describe nursing doctoral
      students' perceptions of factors that impacted them during their doctoral
      program. Answers to an open-ended question, in a national descriptive survey
      study of nursing doctoral students across the United States, were analyzed using
      Colaizzi procedural methods as a guideline. The content analysis identified
      issues unique to doctor of nursing practice (DNP) students that related to lack
      of clarity for the DNP degree and student concerns within academic settings.
      Recommendations include having DNP faculty on DNP project committees and
      standardization of guidelines to ensure rigor and consistency.

PMID- 30096111
TI  - Constructive Feedback Teaching Strategy: A Multisite Study of Its Effectiveness.
AB  - AIM: The study purpose was to describe students' perceptions of feedback after
      participating in a teaching strategy designed to foster a view of feedback as an
      opportunity for improvement. BACKGROUND: Although delivering and receiving
      constructive feedback are essential to the role of the professional nurse,
      feedback has been identified as a trigger for incivility in academia and
      practice. METHOD: Twelve nurse educators from the Quality and Safety Education
      for Nurses Academic Task Force, located at nine schools of nursing across the
      nation, implemented a presentation about giving and receiving constructive
      feedback in junior and senior courses. RESULTS: Five hundred twenty-three
      students submitted a total of 985 posts or essays in response to viewing the
      presentation; seven themes were identified. CONCLUSION: Viewing this teaching
      strategy enabled nursing students to develop an awareness of the opportunity that
      constructive feedback presents for professional development, self-improvement,
      teamwork and collaboration, and patient safety.

PMID- 30096113
TI  - An Enhanced Actualized DNP Model to Improve DNP Project Placements, Rigor, and
      Completion.
AB  - Doctor of nursing practice (DNP) projects are summative evaluations of enactment
      of the DNP Essentials. However, information about structure, process, and
      outcomes of DNP projects is scarce. Guided by an enhanced actualized DNP model,
      this study tested the effect of a PhD-DNP-site mentor model to guide DNP
      projects. Time-to-complete assignments, defense, and graduation improved; high
      satisfaction for students, mentors, and faculty were found; and a strengthened
      academic-practice partnership occurred, leading to additional student placements.
      Broader testing of the enhanced model in various size and types of academic
      practice settings is needed prior to use.

PMID- 30096114
TI  - Exploring the Experiences of DNP-Prepared Nurses Enrolled in a DNP-to-PhD Pathway
      Program.
AB  - The advancement of the doctor of nursing practice (DNP) degree and the need for
      nurse researchers with a doctor of philosophy (PhD) has led to significant growth
      in doctoral nursing education. Some DNP graduates have chosen to pursue a second
      terminal degree. This descriptive study explored the experiences of students
      completing a DNP-to-PhD pathway program. Data analysis revealed that DNP-to-PhD
      students desired acceptance in academia. Implications suggest the need for
      additional pathway programs, clear communication about program outcomes for both
      degrees, formal teaching preparation for all nurse educators, and collaborative
      opportunities for DNP- and PhD-prepared faculty.

PMID- 30096115
TI  - Innovative PhD-DNP Faculty Collaboration to Advance Baccalaureate Student
      Population Health Competencies.
AB  - Entry-level nurses require health promotion, chronic disease self-management,
      care coordination, data utilization, and evidence translation competencies to
      address complex population health needs. An innovative PhD-DNP faculty
      collaboration implemented a descriptive survey design to evaluate simulation
      based strategies using an unfolding chronically ill adult case to address
      population health. Results showed the PhD-DNP faculty team was effective in
      developing clinically meaningful learning experiences to assist baccalaureate
      students to develop population health competencies. This project provides strong
      evidence supporting the value and positive impact of engaging faculty from
      research and practice for future educational research.

PMID- 30096116
TI  - Strategies for Strengthening Ethics Education in a DNP Program.
AB  - Nurse practitioners frequently encounter ethical dilemmas, and their
      identification is essential to effective resolution. An innovative approach
      involving collaboration between doctor of nursing practice (DNP) and doctor of
      philosophy (PhD) faculty was used to address this need in a graduate nursing
      program. The results included a broader understanding of the synergy of the two
      educational backgrounds in translating and delivering evidence-based practices.
      The development and use of realistic case studies was a teaching strategy for
      ethics education. The unique backgrounds of each faculty member promote ethical
      practice among DNP students, which is essential to the profession.

PMID- 30096117
TI  - Innovation With Strengths: A Collaborative Approach to PhD/DNP Integration in
      Doctoral Education.
AB  - Doctorally prepared nurses are well equipped to provide solutions to complex
      issues in today's rapidly changing health care environment. Collaborative
      relationships between doctor of nursing practice (DNP)- and doctor of philosophy
      (PhD)-prepared nurses facilitate timely translation of research into practice,
      enhanced educational opportunities, and development of interventions to improve
      health outcomes; however, challenges have been identified that hinder
      collaboration. This article highlights a three-pronged innovative and structured
      approach to identify individual student strengths, facilitate collaboration among
      DNP and PhD students, and set the foundation for implementation of a strengths
      based curriculum during the doctoral educational experience.

PMID- 30096118
TI  - Doctoral Education: Preparing Our Next Generation for Disruptive Innovation.

PMID- 30096119
TI  - NLN Releases A Vision for Doctoral Faculty Collaboration in Nursing Education.

PMID- 30096120
TI  - Relationships among DNP and PhD Students after Implementing a Doctoral Student
      Organization.

PMID- 30096121
TI  - Breast Implant Mycobacterial Infections: An Epidemiologic Review and Outcome
      Analysis.
AB  - BACKGROUND: Epidemiologic evidence of periprosthetic mycobacterial infections is
      limited. The recent boom in cosmetic surgery tourism has been associated with a
      rise of surgical-site infections in returning patients. This review aims to
      explore available data, examine trends of documented periprosthetic mycobacterial
      infections, and analyze outcomes of management techniques. METHODS: A search in
      the Biosis, Embase, LILACS, MEDLINE, and Web of Science databases from inception
      until December of 2017 for "Breast Implants" and "Mycobacterial Infections" and
      equivalents was performed. Data were pooled after two screening rounds following
      full-text retrieval and cross-referencing. RESULTS: Forty-one reports describing
      171 female patients who had breast prosthesis-related mycobacterial infections
      were identified. Bibliometric case-based analysis revealed a rise of
      periprosthetic mycobacterial infections in developing countries since the start
      of the millennium. The mean patient's age was 37.9 years and the majority of
      patients had undergone bilateral breast augmentation. Most patients presented
      with breast pain or tenderness, after an average incubation period of 9 months.
      Mycobacterium fortuitum was isolated from 90 cases (52.6 percent). Immediate
      explantation with or without delayed reimplantation was the most commonly used
      surgical strategy, complemented by combination antimicrobial therapy for an
      average of 4.6 months. The mean follow-up time was 39.7 months, during which
      recurrence was observed in 21 of 171 patients (12.3 percent). CONCLUSIONS: The
      emergence of periprosthetic mycobacterial infections in relation to cosmetic
      medical tourism alerts clinicians to the importance of educating the public about
      the associated risks. In addition, this study identifies risk factors associated
      with recurrence of periprosthetic mycobacterial infections.

PMID- 30096122
TI  - Subcutaneous Mastectomy Improves Satisfaction with Body and Psychosocial Function
      in Trans Men: Findings of a Cross-Sectional Study Using the BODY-Q Chest Module.
AB  - BACKGROUND: The effectiveness of gender-confirming surgery is best evaluated on
      the basis of patient-reported outcomes. This is the first explorative study using
      the BODY-Q chest module, administered in trans men before and after mastectomy.
      METHODS: Between October of 2016 and May of 2017, trans men were recruited to
      participate in a cross-sectional study. Data collection included standardized
      anamnesis and examination, screening questions on depression/anxiety, and seven
      BODY-Q scales, including new scales measuring satisfaction of the chest and
      nipples. Mean scores for preoperative and postoperative participants were
      compared, and regression analyses were conducted to identify factors associated
      with BODY-Q scores. RESULTS: In total, 101 persons participated (89 percent; 50
      preoperatively and 51 postoperatively). Postoperative participants reported
      significantly higher (better) scores on the chest (67), nipple (58), body (58) (t
      tests, all p < 0.001), and psychological (60) (t test, p = 0.05) scales compared
      with preoperative patients. Postoperative chest and nipple mean scores did not
      differ significantly from a gynecomastia comparison, whereas scores were less
      favorable on the psychosocial domains. Preoperatively, chest scores were not
      associated with objective breast size. Lower postoperative chest scores were
      associated with planned revision surgery (beta = -0.52) and depressive symptoms
      (beta = -0.59). CONCLUSIONS: The present findings indicate that chest and nipple
      satisfaction differences in trans men undergoing mastectomy can be detected using
      the BODY-Q chest module. Future prospective studies are needed to measure
      clinical change in satisfaction and how this relates to changes in other aspects
      of health-related quality of life.

PMID- 30096123
TI  - Hybrid Prepectoral Breast Reconstruction: A Surgical Approach that Combines the
      Benefits of Autologous and Implant-Based Reconstruction.
AB  - BACKGROUND: The advantages of hybrid breast reconstruction (i.e., the combination
      of free tissue transfer with simultaneous implant placement) are well known. In
      an attempt to further minimize morbidity and simplify the procedure, the authors
      have modified their approach in that a prepectoral approach is now routinely
      chosen. METHODS: A retrospective analysis of patients who underwent immediate
      microsurgical breast reconstruction with simultaneous prepectoral implant
      placement was performed. Clinical outcomes and postoperative complications were
      examined. RESULTS: A total of 23 patients with a mean age of 46.6 years (range,
      26 to 72 years) and mean body mass index of 25.8 kg/m (range, 21.4 to 32.1 kg/m)
      underwent reconstruction with 46 free flaps with simultaneous prepectoral
      silicone gel implant placement. The most common implant volume was 210 cc (range,
      150 to 255 cc). Postoperative complications included hematoma [n = 1 (4.3
      percent)], mastectomy skin flap necrosis [n = 5 (21.7 percent)], fat necrosis [n
      = 3 (13 percent)], and delayed wound healing at the flap donor site [n = 4 (17.4
      percent)]. No case of implant malposition, implant infection, flap loss, or "red
      breast" syndrome was encountered during a mean follow-up of 8.4 months (range, 2
      to 17 months). CONCLUSIONS: Prepectoral hybrid breast reconstruction is a safe
      procedure that combines the benefits of autologous and implant-based
      reconstruction. Although the transfer of well-vascularized soft tissue allows
      reconstruction of natural breast ptosis, the addition of an implant provides the
      desired projection, but without being associated with complications such as
      rippling or animation deformity. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, IV.

PMID- 30096124
TI  - Perioperative Ketorolac Use and Postoperative Hematoma Formation in Reduction
      Mammaplasty: A Single-Surgeon Experience of 500 Consecutive Cases.
AB  - BACKGROUND: In light of the escalating opioid crisis, surgeons are increasingly
      focused on minimizing opioid use. Ketorolac has well-documented opioid-sparing
      effects in the postoperative period; however, its use is limited because of
      concerns of postoperative bleeding and hematoma formation. This study explores
      the relationship between hematoma formation and administration of perioperative
      ketorolac in adolescent female patients and young adult women undergoing
      reduction mammaplasty. It also aims to determine the effect of perioperative
      ketorolac administration on the requirement for opioid analgesia. METHODS: The
      authors reviewed the medical records of 500 consecutive female patients who
      underwent reduction mammaplasty for bilateral macromastia from 2007 to 2017. The
      authors collected data pertaining to perioperative analgesia use and
      postoperative hematoma formation. RESULTS: Five-hundred patients were included in
      analyses. The average age of the patients was 18.1 +/- 2.2 years. Three hundred
      eighty-nine patients (77.8 percent) received intravenous ketorolac during the
      perioperative period. Seven patients (1.4 percent) developed a postoperative
      hematoma. Hematoma was not associated with intraoperative, postoperative, and
      perioperative ketorolac use (p > 0.43, all). Intraoperative ketorolac use was
      associated with lower total intraoperative dosing of fentanyl and morphine, and
      postoperative ketorolac use was associated with lower total postoperative doses
      of oxycodone and morphine (p < 0.001, all). CONCLUSIONS: Ketorolac use was
      largely associated with decreased perioperative opioid use, but not with hematoma
      formation. Ketorolac may be a safe alternative to opioids in adolescents and
      young women undergoing reduction mammaplasty without increasing the risk of
      hematoma formation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30096126
TI  - Prognostic Factors Associated with Bone Lymphoma Primarily Presenting in the
      Spine.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To determine the prognostic
      indicators in patients with bone lymphoma of the spine SUMMARY OF BACKGROUND
      DATA.: To date, prognosis for patients with spinal bone lymphoma is based on
      results from small series. Large population-based observational studies are
      lacking. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Registry
      was used to identify all patients with bone lymphoma of the spine from 1995
      through 2014. Overall survival (OS) and disease-specific survival (DSS) estimates
      were obtained using the Kaplan-Meier method and compared across groups using log
      rank test. Association of survival with variables was assessed using Cox
      proportional-hazards regression analysis. Nomograms were established and
      validated by R software. RESULTS: A total of 1338 patients were identified with
      bone lymphoma of the spine. The trend of incidence was relative steady from 1995
      to 2014. The mean and median age of diagnosis was 62.9 and 66.0 years,
      respectively. Men constituted a slightly greater proportion (55.5%) of the
      cohort. The most common subtype of lymphoma was diffuse large B-cell lymphoma
      (59.8%). The 5-year and 10-year OS rates for those patients were 60.6% and 44.7%,
      respectively. Multivariate analysis revealed that age, sex, marital status and
      race were sociodemographic predictors of OS and DSS. Extra-compartmental invasion
      of tumor and Stage IV of lymphoma were significantly corelated with poor OS and
      DSS. Patients without surgery nor radiotherapy was linked to a poor OS. Both OS
      and DSS of patients with spinal bone lymphoma improved in 2005 to 2014 when
      compared to 1995 to 2004. In addition, pre-treatment nomograms to predict 5-year
      and 10-year survival were established. CONCLUSIONS: The findings of this study
      provide population-based estimates of the prognosis for patients with spinal bone
      lymphoma. Both sociodemographic and clinical factors may have an impact on the
      outcomes. LEVEL OF EVIDENCE: 4.

PMID- 30096125
TI  - Identifying Thoracic Compensation and Predicting Reciprocal Thoracic Kyphosis and
      Proximal Junctional Kyphosis in Adult Spinal Deformity Surgery.
AB  - STUDY DESIGN: Retrospective analysis. OBJECTIVE: To define thoracic compensation
      and investigate its association with postoperative reciprocal thoracic kyphosis
      and proximal junctional kyphosis (PJK) SUMMARY OF BACKGROUND DATA.: Adult spinal
      deformity (ASD) patients recruit compensatory mechanisms like pelvic retroversion
      and knee flexion. However, thoracic hypokyphosis is a less recognized
      compensatory mechanism. METHODS: Patients enrolled in a multicenter ASD registry
      undergoing fusions to the pelvis with upper instrumented vertebra (UIV) between
      T9 and L1 were included. Patients were divided into those with postoperative
      reciprocal thoracic kyphosis (reciprocal kyphosis [RK]: change in unfused
      thoracic kyphosis [TK] >=15 degrees ) with and without PJK and those who
      maintained thoracic alignment (MT). Thoracic compensation was defined as expected
      thoracic kyphosis (eTK) minus preoperative TK. RESULTS: For RK (n = 117), the
      mean change in unfused TK was 21.7 degrees  versus 6.1 degrees  for MT (n = 102)
      and the mean PJK angle change was 17.6 degrees  versus 5.7 degrees  for MT (all P
      < 0.001). RK and MT were similar in age, body mass index (BMI), sex, and
      comorbidities. RK had larger preoperative PI-LL mismatch (30.7 vs. 23.6, P =
      0.008) and less preoperative TK (22.3 vs. 30.6, P < 0.001), otherwise sagittal
      vertical axis (SVA), pelvic tilt (PT), and T1 pelvic angle (TPA) were similar. RK
      patients had more preoperative thoracic compensation (29.9 vs. 20.0, P < 0.001),
      more PI-LL correction (29.8 vs. 17.3, P < 0.001), and higher rates of PJK (66%
      vs. 19%, P < 0.001). There were no differences in preoperative health-related
      quality of life (HRQOL) except reciprocal kyphosis (RK) had worse Scoliosis
      Research Society questionnaire (SRS) appearance (2.2 vs. 2.5, P = 0.005). Using a
      logistic regression model, the only predictor for postoperative reciprocal
      thoracic kyphosis was more preoperative thoracic compensation. Postoperatively
      the RK and MT groups were well aligned. Both younger and older (>65 yr) RK
      patients had greater thoracic compensation than MT counterparts. The eTK was not
      significantly different from the postoperative TK for the RK group without PJK (P
      = 0.566). CONCLUSION: The presence of thoracic compensation in adult spinal
      deformity is the primary determinant of postoperative reciprocal thoracic
      kyphosis and these patients have higher rates of proximal junctional kyphosis.
      LEVEL OF EVIDENCE: 3.

PMID- 30096127
TI  - Imatinib-induced drug reaction with eosinophilia and systemic symptoms in solid
      tumors: a patient with dermatofibrosarcoma protuberans and successful
      desensitization management.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe,
      potentially life-threatening drug-induced hypersensitivity reaction,
      characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with
      hypereosinophilia, and elevated liver function tests, which in severe cases may
      lead to fulminant hepatic failure and death. Although DRESS syndrome has been
      associated with over 50 different drugs including imatinib, it has never been
      reported in association with imatinib treatment in solid tumors. We recently
      treated a patient with metastatic dermatofibrosarcoma protuberans, a rare
      cutaneous mesenchymal tumor characterized by constitutive activation of the
      PDGFbeta receptor and high sensitivity to imatinib therapy, who had a DRESS
      reaction to imatinib. Given an initial dramatic clinical and radiological
      response to treatment and lack of effective alternative targeted therapies,
      following imatinib discontinuation and resolution of DRESS, we cautiously
      reintroduced imatinib therapy using a desensitization protocol under the care of
      the allergy and immunologic clinic. Imatinib was carefully titrated from an
      initial dose of 50 mg to a target dose of 400 mg daily, while tapering down the
      prednisone dose. The patient was able to tolerate the treatment without recurrent
      episodes of DRESS or interruptions, and gained additional 6 months of clinical
      benefit from imatinib treatment. Although suspected causative drugs should not be
      reintroduced in DRESS whenever possible, in this case of metastatic disease and
      lack of effective alternative treatments, a carefully designed drug rechallenge
      helped minimize the risk of overt clinical reaction and resulted in an overall
      clinical benefit.

PMID- 30096128
TI  - Inhibition of bromodomain and extraterminal domain reduces growth and invasive
      characteristics of chemoresistant ovarian carcinoma cells.
AB  - Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy
      worldwide. Development of chemoresistance and peritoneal dissemination are the
      major reasons for low survival rate in the patients. The bromodomain and
      extraterminal domain (BET) proteins are known as epigenetic 'readers,' and their
      inhibitors are novel epigenetic strategies for cancer treatment. Accumulating
      body of evidence indicates that epigenetic modifications have critical roles in
      development of EOC, and overexpression of the BET family is a key step in the
      induction of important oncogenes. Here, we examined the mechanistic activity of I
      BET151, a pan-inhibitor of the BET family, in therapy-resistant EOC cells. Our
      findings showed that I-BET151 diminished cell growth, clonogenic potential, and
      induced apoptosis. I-BET151 inhibited cell proliferation through down-modulation
      of FOXM1 and its targets aurora kinase B and cyclin B1. I-BET151 attenuated
      migration and invasion of the EOC cells by down-regulation of epithelial
      mesenchymal transition markers fibronectin, ZEB2, and N-cadherin. I-BET151
      synergistically enhanced cisplatin chemosensitivity by down-regulation of
      survivin and Bcl-2. Our data provide insights into the mechanistic activity of I
      BET151 and suggest that BET inhibition has potential as a therapeutic strategy in
      therapy-resistant EOC. Further in vivo investigations on the therapeutic
      potential of I-BET151 in EOC are warranted.

PMID- 30096129
TI  - hmiR-34c-3p upregulation inhibits the proliferation of colon cancer cells by
      targeting EIF3D.
AB  - Our study desired to investigate how miR-34c-3p regulates colon cancer cell
      proliferation and what is the relationship between miR-34c-3p and EIF3D. HCEpiC
      (normal human colonic epithelial cells), SW620, HT-29, SW480, and HCT-116 (human
      colon cancer cells lines) were used in our study. SW620 cells were chosen and
      divided into blank, miR-34c-3p mimics, miR-34c-3p NC, miR-34c-3p inhibitors, Lv
      EIF3D, Lv-NC, and miR-34c-3p mimics+Lv-EIF3D groups. qRT-PCR was used for the
      detection of miR-34c-3p and EIF3D mRNA expressions. Dual-luciferase reporter
      assay was performed to investigate the effect of miR-34c-3p on EIF3D. Western
      blot was performed to detect EIF3D, cyclin D1, and c-Myc expressions. Clone
      formation and MTT assay were used to measure cell proliferation ability. colon
      cancer cells had lower miR-34c-3p expression, but higher EIF3D expression
      compared with HCEpiC. EIF3D mRNA expression was regulated negatively by miR-34c
      3p. In the miR-34c-3p mimics group, colon cancer cell proliferation was
      significantly decreased, whereas c-Myc and cyclin D1 expressions were
      downregulated. Colon cancer cell proliferation in miR-34c-3p inhibitors and Lv
      EIF3D groups was enhanced, and c-Myc and cyclin D1 expressions were decreased.
      The results suggested that by targeting EIF3D, miR-34c-3p inhibited colon cancer
      cell proliferation.

PMID- 30096130
TI  - N400 amplitude does not recover from disappearance after repetitions despite
      reinitiated semantic integration difficulty.
AB  - It remains an open question whether the amplitude of N400 reflects combinatory
      postlexical semantic integration processing. To examine the issue, we repeatedly
      presented strictly simplified, N400-eliciting three-word structures for seven
      times, mixed with their plausible counterparts, followed immediately by a much
      more enriched and informative sentence containing two keywords of the incongruous
      structure, for the purpose of reinitiating semantic integration processing. Event
      related potentials were recorded and compared at the first, fourth, seventh, and
      eighth time. It was found that multiple repetitions attenuated the N400 effect to
      almost nonexistent and that the follow-up semantic integration reinitiating
      sentence did not recover N400 amplitude. The results suggest that combinatory
      postlexical semantic integration does not significantly modulate N400 amplitude,
      and provide evidence for noncombinatory processes underlying N400 such as
      automatic spreading activation and expectancy/prediction.

PMID- 30096131
TI  - Effects of ginkgo biloba extract on the cognitive function and expression profile
      of inflammatory factors in a rat model of hemorrhagic stroke.
AB  - Hemorrhagic stroke is a major risk factor for cognitive impairment. Our study
      aimed to measure the effect of ginkgo biloba extract (EGB761) on the cognitive
      ability and inflammatory expression in hemorrhagic stroke model SD rats and to
      analyze their relationship. Forty SD rats were divided randomly into an SD group
      (normal control SD rats), an SD+EGB761 group (normal control SD rats supplemented
      with 45 mg/kg EGB761), a CO group (hemorrhagic stroke model SD rats using
      collagenase), and a CO+EGB761 group (hemorrhagic stroke model SD rats
      supplemented with 45 mg/kg EGB761) consisting of 10 rats, respectively. The Y
      electric maze test was selected to measure the cognitive function in four groups.
      Furthermore, enzyme-linked immunosorbent assay and real-time PCR were,
      respectively, applied for detecting the protein and gene expression profiles of
      inflammatory factors in primary cultured microglia. Compared with rats in the SD
      group, the average time of electrical simulation for mastering criteria was
      prolonged in the CO group (P<0.05). Furthermore, expression levels of
      proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, and tumor necrosis
      factor-alpha and anti-inflammatory cytokines IL-4, IL-10, and tumor necrosis
      factor-beta were significantly increased and decreased, respectively, in rats of
      the CO group compared with the SD group (P<0.05). The results of electrical
      simulation time, inflammatory factors protein, and gene expression profile in
      rats of the CO+EGB761 group compared with the CO group were opposite to above
      contrast (P<0.05). Ginkgo biloba extract could alleviate the cognitive
      dysfunction after hemorrhagic stroke in SD rats; this is associated with
      regulating the expression of inflammatory factors secreted by microglia.

PMID- 30096132
TI  - Relationship Between the Incidence of Road Traffic Accidents, Psychological
      Characteristics, and Genotype in Bus Drivers in a Chinese Population.
AB  - BACKGROUND The aim of this study was to determine the association between the
      incidence of road traffic accidents, psychological characteristics, and genotype
      in bus drivers in a Chinese population. MATERIAL AND METHODS Bus drivers who had
      been involved in road traffic accidents (n=106) (the study group), and bus
      drivers with no history of road traffic accidents (n=106) (the control group)
      completed demographic questionnaires, the Eysenck Personality Questionnaire (EPQ)
      and the Type-A behavior pattern (TABP) evaluation. Serum 5-hydroxytryptamine (5
      HT) (serotonin), and 5-hydroxytryptophan (5-HTP) levels were measured by high
      performance liquid chromatography-fluorescent detection (HPLC-FLD). Serotonin
      transporter promoter-linked polymorphism region (5-HTTLPR) and the 521 C/T single
      nucleotide polymorphism (SNP) in the regulatory region of the dopamine D4
      receptor gene (DRD4-521 C/T) were measured using polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP). RESULTS After accounting for
      potential confounders, extroversion, psychopathy, neuroticism and time hurrying
      (impatience) were significant factors associated with road traffic accidents in
      bus drivers (adjusted OR: 1.268, 95% CI: 1.133-1.419; adjusted OR: 1.177, 95% CI:
      1.028-1.347; adjusted OR: 1.092, 95% CI: 1.005-1.187; adjusted OR: 1.123, 95% CI:
      1.025-1.230, respectively). Reduced serum levels of 5-HT and 5-HTP were
      significantly associated with the incidence of road traffic accidents (adjusted
      OR: 0.985, 95% CI: 0.973-0.997; adjusted OR: 0.982, 95% CI: 0.969-0.994,
      respectively). CONCLUSIONS Psychological characteristics associated with the 5
      HTTLPR and DRD4-521 C/T genotypes, including extroversion, psychopathy,
      neuroticism, and time hurrying (impatience), and low serum levels of 5-HT and 5
      HTP in bus drivers were associated with an increased risk of road traffic
      accidents.

PMID- 30096133
TI  - Genetic architecture of gene expression traits across diverse populations.
AB  - For many complex traits, gene regulation is likely to play a crucial mechanistic
      role. How the genetic architectures of complex traits vary between populations
      and subsequent effects on genetic prediction are not well understood, in part due
      to the historical paucity of GWAS in populations of non-European ancestry. We
      used data from the MESA (Multi-Ethnic Study of Atherosclerosis) cohort to
      characterize the genetic architecture of gene expression within and between
      diverse populations. Genotype and monocyte gene expression were available in
      individuals with African American (AFA, n = 233), Hispanic (HIS, n = 352), and
      European (CAU, n = 578) ancestry. We performed expression quantitative trait loci
      (eQTL) mapping in each population and show genetic correlation of gene expression
      depends on shared ancestry proportions. Using elastic net modeling with cross
      validation to optimize genotypic predictors of gene expression in each
      population, we show the genetic architecture of gene expression for most
      predictable genes is sparse. We found the best predicted gene in each population,
      TACSTD2 in AFA and CHURC1 in CAU and HIS, had similar prediction performance
      across populations with R2 > 0.8 in each population. However, we identified a
      subset of genes that are well-predicted in one population, but poorly predicted
      in another. We show these differences in predictive performance are due to allele
      frequency differences between populations. Using genotype weights trained in MESA
      to predict gene expression in independent populations showed that a training set
      with ancestry similar to the test set is better at predicting gene expression in
      test populations, demonstrating an urgent need for diverse population sampling in
      genomics. Our predictive models and performance statistics in diverse cohorts are
      made publicly available for use in transcriptome mapping methods at
      https://github.com/WheelerLab/DivPop.

PMID- 30096134
TI  - Heterogeneity and longevity of antibody memory to viruses and vaccines.
AB  - Determining the duration of protective immunity requires quantifying the
      magnitude and rate of loss of antibodies to different virus and vaccine antigens.
      A key complication is heterogeneity in both the magnitude and decay rate of
      responses of different individuals to a given vaccine, as well as of a given
      individual to different vaccines. We analyzed longitudinal data on antibody
      titers in 45 individuals to characterize the extent of this heterogeneity and
      used models to determine how it affected the longevity of protective immunity to
      measles, rubella, vaccinia, tetanus, and diphtheria. Our analysis showed that the
      magnitude of responses in different individuals varied between 12- and 200-fold
      (95% coverage) depending on the antigen. Heterogeneity in the magnitude and decay
      rate contribute comparably to variation in the longevity of protective immunity
      between different individuals. We found that some individuals have, on average,
      slightly longer-lasting memory than others-on average, they have higher antibody
      levels with slower decay rates. We identified different patterns for the loss of
      protective levels of antibodies to different vaccine and virus antigens.
      Specifically, we found that for the first 25 to 50 years, virtually all
      individuals have protective antibody titers against diphtheria and tetanus,
      respectively, but about 10% of the population subsequently lose protective
      immunity per decade. In contrast, at the outset, not all individuals had
      protective titers against measles, rubella, and vaccinia. However, these antibody
      titers wane much more slowly, with a loss of protective immunity in only 1% to 3%
      of the population per decade. Our results highlight the importance of long-term
      longitudinal studies for estimating the duration of protective immunity and
      suggest both how vaccines might be improved and how boosting schedules might be
      reevaluated.

PMID- 30096136
TI  - Antipsychotic prescribing patterns on admission to and at discharge from a
      tertiary care program for treatment-resistant psychosis.
AB  - Retrospective data were collected from 330 individuals who were treated at a
      tertiary care program for treatment-resistant psychosis between 1994 and 2010.
      The main objectives were to compare the use of antipsychotic monotherapy to
      polypharmacy and to characterize within-individual changes in treatment and
      symptomatology between admission and discharge. At admission, individuals who
      were prescribed only one antipsychotic were comparable to those who were
      prescribed at least two antipsychotics with regard to demographics and symptom
      severity. The use of psychotropic medications other than antipsychotics was also
      similar between the two groups. However, the magnitude of antipsychotic
      utilization was greater in individuals who were receiving antipsychotic
      polypharmacy. In addition, a greater proportion received excessive doses at
      admission. Similar findings were observed when the two antipsychotic prescribing
      practices were compared at discharge. Three important patterns were identified
      when investigating within-individual changes. First, fewer individuals were
      prescribed more than one antipsychotic at discharge. This was accompanied by a
      general decrease in the magnitude of antipsychotic utilization. Second, the
      number of individuals who were prescribed clozapine had increased by discharge.
      Most who were already prescribed clozapine at admission had their doses
      increased. Third, improvements in symptomatology were observed across all of the
      subscales included in the Positive and Negative Symptom Scale (PANSS); 57.9% of
      individuals experienced a relative reduction in total PANSS scores exceeding 20%.
      Based on these findings, it is possible to alleviate symptom severity while
      reducing antipsychotic utilization when patients are treated at a tertiary care
      program for treatment-resistant psychosis.

PMID- 30096137
TI  - Correction: Estimating retention in HIV care accounting for patient transfers: A
      national laboratory cohort study in South Africa.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1002589.].

PMID- 30096135
TI  - Transcriptional programming of lipid and amino acid metabolism by the skeletal
      muscle circadian clock.
AB  - Circadian clocks are fundamental physiological regulators of energy homeostasis,
      but direct transcriptional targets of the muscle clock machinery are unknown. To
      understand how the muscle clock directs rhythmic metabolism, we determined genome
      wide binding of the master clock regulators brain and muscle ARNT-like protein 1
      (BMAL1) and REV-ERBalpha in murine muscles. Integrating occupancy with 24-hr gene
      expression and metabolomics after muscle-specific loss of BMAL1 and REV-ERBalpha,
      here we unravel novel molecular mechanisms connecting muscle clock function to
      daily cycles of lipid and protein metabolism. Validating BMAL1 and REV-ERBalpha
      targets using luciferase assays and in vivo rescue, we demonstrate how a major
      role of the muscle clock is to promote diurnal cycles of neutral lipid storage
      while coordinately inhibiting lipid and protein catabolism prior to awakening.
      This occurs by BMAL1-dependent activation of Dgat2 and REV-ERBalpha-dependent
      repression of major targets involved in lipid metabolism and protein turnover
      (MuRF-1, Atrogin-1). Accordingly, muscle-specific loss of BMAL1 is associated
      with metabolic inefficiency, impaired muscle triglyceride biosynthesis, and
      accumulation of bioactive lipids and amino acids. Taken together, our data
      provide a comprehensive overview of how genomic binding of BMAL1 and REV-ERBalpha
      is related to temporal changes in gene expression and metabolite fluctuations.

PMID- 30096139
TI  - Towards 90-90: Findings after two years of the HPTN 071 (PopART) cluster
      randomized trial of a universal testing-and-treatment intervention in Zambia.
AB  - BACKGROUND: HPTN071(PopART) is a 3-arm community-randomised study in 21 peri
      urban/urban communities in Zambia and the Western Cape of South Africa, with high
      HIV prevalence and high mobility especially among young adults. In Arm A
      communities, from November 2013 community HIV care providers (CHiPs) have
      delivered the "PopART" universal-test-and-treat (UTT) package in annual rounds,
      during which they visit all households and offer HIV testing. CHiPs refer HIV
      positive (HIV+) individuals to routine HIV clinic services, where universal ART
      (irrespective of CD4 count) is offered, with re-visits to support linkage to
      care. The overall goal is to reduce population-level adult HIV incidence, through
      achieving high HIV testing and treatment coverage. METHODS AND FINDINGS: The
      second annual round was June 2015-October 2016. Included in analysis are all
      individuals aged >=15 years who consented to participate, with extrapolation to
      the total population. Our three main outcomes are (1) knowledge of HIV+ status
      (2) ART coverage, by the end of Round 2 (R2) and compared with the start of R2,
      and (3) retention on ART on the day of consenting to participate in R2. We used
      "time-to-event" methods to estimate the median time to start ART after referral
      to care. CHiPs visited 45,631 households during R2, ~98% of the estimated total
      across the four communities, and for 94% (43,022/45,631) consent was given for
      all household members to be listed on the CHiPs' electronic register; 120,272
      individuals aged >=15 years were listed, among whom 64% of men (37,265/57,901)
      and 86% (53,516/62,371) of women consented to participate in R2. We estimated
      there were 6,521 HIV+ men and 10,690 HIV+ women in the total population of
      visited households; and that ~80% and ~90% of HIV+ men and women respectively
      knew their HIV+ status by the end of R2, fairly similar across age groups but
      lower among those who did not participate in Round 1 (R1). Among those who knew
      their HIV+ status, ~80% of both men and women were on ART by the end of R2, close
      to 90% among men aged >=45 and women aged >=35 years, but lower among younger
      adults, those who were resident in R1 but did not participate in R1, and those
      who were newly resident in the area of the community in which they were living in
      R2. Overall ART coverage was ~65% among HIV+ men and ~75% among HIV+ women,
      compared with the cumulative 90-90 target of 81%. Among those who reported ever
      taking ART, 93% of men and 95% of women self-reported they were on ART and missed
      0 pills in the last 3 days. The median time to start ART after referral to care
      was ~6 months in R2, similar across the age range 25-54 years, compared with ~9.5
      months in R1. The two main limitations to our findings were that a comparison
      with control-arm communities cannot be made until the end of the study; and that
      to extrapolate to the total population, assumptions were required about
      individuals who were resident, but did not participate, in R2. CONCLUSIONS:
      Overall coverage against the 90-90 targets was high after two years of
      intervention, but was lower among men, individuals aged 18-34 years, and those
      who did not participate in R1. Our findings reflect the relative difficulties for
      CHiPs to contact men at home, compared with women, and that it is challenging to
      reach high levels of testing and treatment coverage in communities with
      substantial mobility and in-migration. The shortened time to start ART after
      referral to care in R2, compared with R1, was likely attributable to multiple
      factors including an increased focus of the CHiPs on linkage to care; increasing
      community acceptance and understanding of the CHiPs, and of ART and UTT, with
      time; increased coordination with the clinics to facilitate linkage; and clinic
      improvements.

PMID- 30096138
TI  - Transcriptome analysis of adult Caenorhabditis elegans cells reveals tissue
      specific gene and isoform expression.
AB  - The biology and behavior of adults differ substantially from those of developing
      animals, and cell-specific information is critical for deciphering the biology of
      multicellular animals. Thus, adult tissue-specific transcriptomic data are
      critical for understanding molecular mechanisms that control their phenotypes. We
      used adult cell-specific isolation to identify the transcriptomes of C. elegans'
      four major tissues (or "tissue-ome"), identifying ubiquitously expressed and
      tissue-specific "enriched" genes. These data newly reveal the hypodermis'
      metabolic character, suggest potential worm-human tissue orthologies, and
      identify tissue-specific changes in the Insulin/IGF-1 signaling pathway. Tissue
      specific alternative splicing analysis identified a large set of collagen
      isoforms. Finally, we developed a machine learning-based prediction tool for 76
      sub-tissue cell types, which we used to predict cellular expression differences
      in IIS/FOXO signaling, stage-specific TGF-beta activity, and basal vs. memory
      induced CREB transcription. Together, these data provide a rich resource for
      understanding the biology governing multicellular adult animals.

PMID- 30096140
TI  - A comparative ultrastructure study of storage cells in the eutardigrade
      Richtersius coronifer in the hydrated state and after desiccation and heating
      stress.
AB  - Tardigrades represent an invertebrate phylum with no circulatory or respiratory
      system. Their body cavity is filled with free storage cells of the coelomocyte
      type, which are responsible for important physiological functions. We report a
      study comparing the ultrastructure of storage cells in anhydrobiotic and hydrated
      specimens of the eutardigrade Richtersius coronifer. We also analysed the effect
      of temperature stress on storage cell structure. Firstly, we verified two types
      of ultrastructurally different storage cells, which differ in cellular organelle
      complexity, amount and content of reserve material and connection to oogenetic
      stage. Type I cells were found to differ ultrastructurally depending on the
      oogenetic stage of the animal. The main function of these cells is energy
      storage. Storage cells of Type I were also observed in the single male that was
      found among the analysed specimens. The second cell type, Type II, found only in
      females, represents young undifferentiated cells, possibly stem cells. The two
      types of cells also differ with respect to the presence of nucleolar vacuoles,
      which are related to oogenetic stages and to changes in nucleolic activity during
      oogenesis. Secondly, this study revealed that storage cells are not
      ultrastructurally affected by six months of desiccation or by heating following
      this desiccation period. However, heating of the desiccated animals (tuns) tended
      to reduce animal survival, indicating that long-term desiccation makes these
      animals more vulnerable to heat stress. We confirmed the degradative pathways
      during the rehydration process after desiccation and heat stress. Our study is
      the first to document two ultrastructurally different types of storage cells in
      tardigrades and reveals new perspectives for further studies of tardigrade
      storage cells.

PMID- 30096142
TI  - The prognostic significance of lymph node size in node-positive colon cancer.
AB  - OBJECTIVES: To (i) show the outcome benefits of enlarged lymph nodes in node
      positive colon cancer cases, as it was shown previously in negative node cases;
      (ii) disprove the stage migration theory and (iii) list the factors affecting
      lymph node size and yield. METHODS: A retrospective study including 234 node
      positive colon cancer cases was scheduled and performed. All recovered lymph
      nodes (6969) from 234 cases were microscopically examined in regard to (a) lymph
      node size (b) presence of metastasis (c) extent of intra-nodal metastasis. On the
      basis of resulting data, a statistical analysis was performed. RESULTS:
      Metastases occurred in all size categories, though more often in larger lymph
      nodes. Fifty-one percent of all metastasised nodes were 2 to 6 mm in size.
      Approximately half of all nodes >10 mm were microscopically free of cancer. Cases
      with a small lymph node metastasis to lymph node size ratio (MSR) had a better
      prognosis than others: 85 months (95% CI: 72-97) vs. 67 months (95% CI: 47-88), p
      <0.001 (mean, overall survival). To differentiate between cases with the same
      ratio but different absolute lymph nodes sizes, we divided the cases into two
      groups that differed in their number of moderate to large lymph nodes. The group
      with more moderate to large lymph nodes showed a clear outcome benefit: 104
      months (95% CI: 86-122) vs. 66 months (95% CI: 54-77), p = 0.014 (mean, overall
      survival). CONCLUSIONS: Metastasised lymph nodes affect all size categories, and
      large lymph nodes are not always metastasised. The combination of enlarged lymph
      nodes and a small lymph node metastasis to lymph node size ratio (MSR) is
      associated with a better prognosis than others. When enlarged lymph nodes were
      considered as surrogate markers of an effective local immune response due to
      nodal hyperplasia, the immune system could be seen as the confounder affecting
      both lymph node size and prognosis. Our results are pointing in this direction
      and, along with other reasons, are challenging the stage migration theory.

PMID- 30096141
TI  - Patterns in first and daily cigarette initiation among youth and young adults
      from 2002 to 2015.
AB  - This study's objective was to describe long-term trends and patterns in first
      cigarette use (cigarette initiation) and daily cigarette use (daily initiation)
      among youth and young adults in the U.S. We used cross-sectional survey data from
      the National Survey on Drug Use and Health, 2002-2015, to estimate annual
      incidence of first cigarette use (N = 270,556) and first daily cigarette use (N =
      373,464) for each year by age groups, race/ethnicity and gender, examining trends
      over time and the average annual change in initiation for each group. Several
      clear patterns emerged: 1) cigarette initiation and daily initiation
      significantly decreased over time among those aged 12-14 and 15-17 and these
      trends were consistent among nearly all racial/ethnic and gender subgroups; 2)
      among 18-21 year olds, cigarette initiation sharply increased through 2009,
      surpassing rates among 15-17 year olds, and sharply declined through 2015 while
      remaining higher than rates among the younger group, and this trend was
      consistent for almost all racial/ethnic subgroups; 3) daily initiation for those
      aged 18-21 significantly declined, and this was significant among most subgroups
      4) there was no change in cigarette initiation and daily initiation for 22-25
      year olds overall and most subgroups; 5) there was a significant increase in
      cigarette initiation for 22-25 year old Hispanics males and daily initiation for
      22-25 year old males. This study provides a comprehensive look at trends in
      cigarette and daily initiation among U.S. youth and young adults. Despite notable
      declines in smoking initiation among youth and young adult populations over the
      last two decades, targeted prevention and policy efforts are needed for subgroups
      at higher risk, including young adults and Hispanic males.

PMID- 30096143
TI  - A non-cell-autonomous actin redistribution enables isotropic retinal growth.
AB  - Tissue shape is often established early in development and needs to be scaled
      isotropically during growth. However, the cellular contributors and ways by which
      cells interact tissue-wide to enable coordinated isotropic tissue scaling are not
      yet understood. Here, we follow cell and tissue shape changes in the zebrafish
      retinal neuroepithelium, which forms a cup with a smooth surface early in
      development and maintains this architecture as it grows. By combining 3D analysis
      and theory, we show how a global increase in cell height can maintain tissue
      shape during growth. Timely cell height increase occurs concurrently with a non
      cell-autonomous actin redistribution. Blocking actin redistribution and cell
      height increase perturbs isotropic scaling and leads to disturbed, folded tissue
      shape. Taken together, our data show how global changes in cell shape enable
      isotropic growth of the developing retinal neuroepithelium, a concept that could
      also apply to other systems.

PMID- 30096144
TI  - Factors explaining variation in self-esteem among persons with type 1 diabetes
      and elevated HbA1c.
AB  - OBJECTIVES: To investigate associations between perceived autonomy support from
      health-care professionals, autonomy-driven motivation, diabetes self-perceived
      competence and self-esteem in adults (age 18-55 yrs) with suboptimally regulated
      type 1 diabetes mellitus (T1DM) with at least one HbA1c>=8.0% (>=64 mmol/mol)
      during the past year, and whether these factors could predict decrease in self
      esteem over time. METHODS: A cross-sectional population-based survey was
      performed, and 9 months follow-up data were collected. Data collection comprised
      clinical and socio-demographic variables, blood sampling (HbA1c) and self-report
      questionnaires; the Health Care Climate Questionnaire (HCCQ), Treatment Self
      Regulation Questionnaire (TSRQ), the Perceived Competence in Diabetes Scale
      (PCDS), and the Rosenberg Self-esteem Scale (RSES). We fitted block-wise linear
      regression models to assess associations between RSES and variables of interest
      (HCCQ, TSRQ, PCDS, HbA1c, clinical and socio-demographic variables) and linear
      regression models to assess predictors of change over time. FINDINGS: In this
      study sample, aged 36.7 (+/-10.7) mean HbA1c 9.3% (+/-1.1), 31.5% had long-term
      complications and 42.7% had experienced severe hypoglycemia within the previous
      12 months. In the final regression model the association between PCDS and RSES
      was strongly significant (B = 1.99, p<0.001) and the associations between HCCQ,
      TSRQ and RSES were reduced to non-significance. All predictor variables combined
      explained 42% of the variability of RSES (adjusted R2 = 0.423) with PCDS
      contributing 18% to explained variance (R-square change = 0.184, p<0.001). The
      strongest predictors of change in RSES over time were long-term complications (B
      = 2.76, p<0.001), specifically foot-related problems, and being female (B = 
      2.16, p = 0.002). CONCLUSIONS: Perceived autonomy support, autonomy-driven
      motivation and diabetes self-perceived competence play a significant role in
      explaining self-esteem among adults with suboptimally regulated T1DM. Healthcare
      professionals should acknowledge self-esteem as a valuable factor in
      understanding the multifaceted health choices people with T1DM make. TRIAL
      REGISTRATION: Clinical Trials.gov with identification number NCT 01317459.

PMID- 30096146
TI  - Spatial distribution and losses by grain destroying insects in transgenic corn
      expressing the toxin Cry1Ab.
AB  - Insect pests are one of the factors that most impact plant yield. The magnitude
      of the losses and the spatiotemporal pest distribution in crops is a result of
      their interactions with the environment. Therefore, the understanding of the
      causes of production losses and the pest spatial patterns is important for the
      development of suitable sampling plans and pest management programs. Thus, this
      study aimed to quantify grain losses caused by insects and to determine the
      spatial distribution pattern of arthropod pest species in Bt and non-Bt corn. The
      prevailing insect pests in the corn ears were the earworm and fall armyworm
      caterpillars (Helicoverpa spp. and Spodoptera frugiperda), the cornsilk fly
      (Euxesta spp.), the maize weevil (Sitophilus zeamais), and the square-necked
      grain beetle (Cathartus quadricollis). The non-Bt corn was more attacked by the
      caterpillars and the weevil, while Bt corn was more affected by the cornsilk fly
      Euxesta spp. Spatial dependence was significant for the damage caused by the
      caterpillars, the grain beetle and the maize weevil in both the Bt and non-Bt
      corn genotypes. The range of the damage caused by the insects was between 9.0-9.7
      m for the caterpillars, 6.9-12.20 m for the cornsilk fly, 10.7-80.4 m for the
      square-necked grain beetle, and 51.9-170.7 m for the maize weevil. The pattern of
      the spatial distribution of pest damage in both corn genotypes (i.e., Bt and non
      Bt corn) was similar with a prevalence of moderate to strong spatial dependence
      and aggregate damage distribution. The plants near to the sampling points
      exhibited injury and infestation levels similar to those of the sampled plants.

PMID- 30096145
TI  - Loci and natural alleles underlying robust roots and adaptive domestication of
      upland ecotype rice in aerobic conditions.
AB  - A robust (long and thick) root system is characteristic of upland japonica rice
      adapted to drought conditions. Using deep sequencing and large scale phenotyping
      data of 795 rice accessions and an integrated strategy combining results from
      high resolution mapping by GWAS and linkage mapping, comprehensive analyses of
      genomic, transcriptomic and haplotype data, we identified large numbers of QTLs
      affecting rice root length and thickness (RL and RT) and shortlisted relatively
      few candidate genes for many of the identified small-effect QTLs. Forty four and
      97 QTL candidate genes for RL and RT were identified, and five of the RL QTL
      candidates were validated by T-DNA insertional mutation; all have diverse
      functions and are involved in root development. This work demonstrated a powerful
      strategy for highly efficient cloning of moderate- and small-effect QTLs that is
      difficult using the classical map-based cloning approach. Population analyses of
      the 795 accessions, 202 additional upland landraces, and 446 wild rice accessions
      based on random SNPs and SNPs within robust loci suggested that there could be
      much less diversity in robust-root candidate genes among upland japonica
      accessions than in other ecotypes. Further analysis of nucleotide diversity and
      allele frequency in the robust loci among different ecotypes and wild rice
      accessions showed that almost all alleles could be detected in wild rice, and
      pyramiding of robust-root alleles could be an important genetic characteristic of
      upland japonica. Given that geographical distribution of upland landraces, we
      suggest that during domestication of upland japonica, the strongest pyramiding of
      robust-root alleles makes it a unique ecotype adapted to aerobic conditions.

PMID- 30096147
TI  - Male partners of young women in Uganda: Understanding their relationships and use
      of HIV testing.
AB  - BACKGROUND: Substantial concern exists about the high risk of sexually
      transmitted HIV to adolescent girls and young women (AGYW, ages 15-24) in Eastern
      and Southern Africa. Yet limited research has been conducted with AGYW's male
      sexual partners regarding their perspectives on relationships and strategies for
      mitigating HIV risk. We sought to fill this gap in order to inform the DREAMS
      Partnership and similar HIV prevention programs in Uganda. METHODS: We conducted
      94 in-depth interviews, from April-June 2017, with male partners of AGYW in three
      districts: Gulu, Mukono, and Sembabule. Men were recruited at community venues
      identified as potential transmission areas, and via female partners enrolled in
      DREAMS. Analyses focused on men's current and recent partnerships and HIV service
      use. RESULTS: Most respondents (80%) were married and 28 years old on average.
      Men saw partner concurrency as pervasive, and half described their own current
      multiple partners. Having married in their early 20s, over time most men
      continued to seek out AGYW as new partners, regardless of their own age.
      Relationships were highly fluid, with casual short-term partnerships becoming
      more formalized, and more formalized partnerships characterized by periods of
      separation and outside partnerships. Nearly all men reported recent HIV testing
      and described testing at distinct relationship points (e.g., when deciding to
      continue a relationship/get married, or when reuniting with a partner after a
      separation). Testing often stemmed from distrust of partner behavior, and an HIV
      negative status served to validate respondents' current relationship practices.
      CONCLUSIONS: Across the three regions in Uganda, findings with partners of AGYW
      confirm earlier reports in Uganda of multiple concurrent partnerships, and
      demonstrate substantial HIV testing. Yet they also unearth the degree to which
      these partnerships are fluid (switching between casual and/or more long-term
      partnerships), which complicates potential HIV prevention strategies. Context
      specific findings around these partnerships and risk are critical to further
      tailor HIV prevention programs.

PMID- 30096148
TI  - Contraceptive uptake in post abortion care-Secondary outcomes from a randomised
      controlled trial, Kisumu, Kenya.
AB  - AIM: The aim was to explore contraceptive uptake, associated factors and
      satisfaction among post abortion-care (PAC) seeking women in Kenya. Due to unsafe
      abortions, almost 120 000 Kenyan women received PAC in 2012, and of these women,
      70% did not use contraception before pregnancy. METHODS: This study was nested in
      a larger randomised controlled trial, where 859 women sought PAC at two public
      hospitals in Kisumu, in June 2013-May 2016. The women were randomly assigned to a
      midwife or a physician for PAC, including contraceptive counselling, and followed
      up at 7-10 days and three months. Associated factors for contraceptive uptake
      were analysed with binary logistic regression, and contraceptive method choice,
      adherence and satisfaction level were examined by descriptive statistics, using
      IBM SPSS Statistics for Windows, Version 22.0. RESULTS: Out of the 810 PAC
      seeking women, 76% (n = 609) accepted the use of contraception. Age groups of 21
      25 (OR: 2.35; p < 0.029) and 26-30 (OR: 2.22; p < 0.038), and previous experience
      of 1-2 gravidities (OR 1.939; p = 0.018) were independent factors associated with
      the up-take. Methods used: injections 39% (n = 236); pills 27% (n = 166); condoms
      25% (n = 151); implant 7% (n = 45) and intrauterine device (IUD) 1% (n = 8). At 3
      month follow-up of the women (470/609; 77%), 354 (75%) women still used
      contraception, and most (n = 332; 94%) were satisfied with the method. Reasons
      for discontinuation were side-effects (n = 44; 39%), partner refusal (n = 27;
      24%), planned pregnancy (n = 27; 24%) and lack of resupplies (n = 15; 13%).
      CONCLUSIONS: PAC-seeking women seem highly motivated to use contraceptives, yet a
      quarter decline the use, and at 3-month follow-up a further quarter among the
      users had discontinued. Implant, IUD and permanent method are rarely used.
      Strategies to improve contraceptive counselling, particularly to adolescent
      girls, and to increase access to a wide range of methods, as well as provider
      training and supervision may help to improve contraceptive acceptance and
      compliance among PAC-seeking women in Kisumu, Kenya.

PMID- 30096150
TI  - Meta-analysis of postoperative adjuvant therapy for small bowel adenocarcinoma.
AB  - OBJECTIVE: The role of adjuvant therapy in small bowel adenocarcinoma (SBA), a
      rare malignancy with a poor prognosis, is controversial. The purpose of this
      article is to investigate the impact of adjuvant therapy on the survival of
      patients with SBA in a meta-analysis. METHODS: We performed a comprehensive
      search of PubMed, EMBASE and the Cochrane Library database between 2010 and 2017.
      Hazard ratios (HR) with 95% confidence intervals (95%CI) were used to assess the
      effect of adjuvant chemotherapy and/or radiation treatment after curative surgery
      in patients with SBA. Moreover, impact of age, sex, stage, differentiation, lymph
      node involvement, and margin status was also evaluated. RESULTS: We included 15
      studies to evaluate the effect of adjuvant therapy on the survival of patients
      with SBA. The pooled HR of overall survival (OS) involving 5986 patients showed
      that adjuvant therapy did not have a statistically significant effect on the
      survival of patients with SBA (pooled HR = 0.89, 95% CI = 0.73-1.09, p = 0.25).
      Further, 607 patients with duodenal adenocarcinoma (DA) had similar results
      (pooled HR = 0.96, 95% CI = 0.75-1.23, p = 0.77). Similarly, adjuvant treatment
      vs. non-adjuvant treatment in terms of disease-free survival (DFS) or relapse
      free survival (RFS) showed the same results (pooled HR = 0.89, 95% CI = 0.64
      1.23, p = 0.48). However, we found that adjuvant therapy resulted in favorable
      postoperative survival in Europe according to the subgroup analysis (pooled HR =
      0.63, 95% CI = 0.5-0.8, p = 0.0002). In addition, the pooled HR shows that stage,
      differentiation, lymph node involvement, and margin status were related to the OS
      of patients with SBA. CONCLUSION: Patients with SBA who received adjuvant therapy
      after surgery did not receive a significant survival benefit. Adjuvant therapy
      may be more useful in advanced cancer or metastatic patients.

PMID- 30096149
TI  - Transcription factor ASCL2 is required for development of the glycogen
      trophoblast cell lineage.
AB  - The basic helix-loop-helix (bHLH) transcription factor ASCL2 plays essential
      roles in diploid multipotent trophoblast progenitors, intestinal stem cells,
      follicular T-helper cells, as well as during epidermal development and
      myogenesis. During early development, Ascl2 expression is regulated by genomic
      imprinting and only the maternally inherited allele is transcriptionally active
      in trophoblast. The paternal allele-specific silencing of Ascl2 requires
      expression of the long non-coding RNA Kcnq1ot1 in cis and the deposition of
      repressive histone marks. Here we show that Del7AI, a 280-kb deletion allele
      neighboring Ascl2, interferes with this process in cis and leads to a partial
      loss of silencing at Ascl2. Genetic rescue experiments show that the low level of
      Ascl2 expression from the paternal Del7AI allele can rescue the embryonic
      lethality associated with maternally inherited Ascl2 mutations, in a level
      dependent manner. Despite their ability to support development to term, the
      rescued placentae have a pronounced phenotype characterized by severe hypoplasia
      of the junctional zone, expansion of the parietal trophoblast giant cell layer,
      and complete absence of invasive glycogen trophoblast cells. Transcriptome
      analysis of ectoplacental cones at E7.5 and differentiation assays of Ascl2
      mutant trophoblast stem cells show that ASCL2 is required for the emergence or
      early maintenance of glycogen trophoblast cells during development. Our work
      identifies a new cis-acting mutation interfering with Kcnq1ot1 silencing function
      and establishes a novel critical developmental role for the transcription factor
      ASCL2.

PMID- 30096151
TI  - Distinct parafacial regions in control of breathing in adult rats.
AB  - Recently, based on functional differences, we subdivided neurons juxtaposed to
      the facial nucleus into two distinct populations, the parafacial ventral and
      lateral regions, i.e., pFV and pFL. Little is known about the composition of
      these regions, i.e., are they homogenous or heterogeneous populations? Here, we
      manipulated their excitability in spontaneously breathing vagotomized urethane
      anesthetized adult rats to further characterize their role in breathing. In the
      pFL, disinhibition or excitation decreased breathing frequency (f) with a
      concomitant increase of tidal volume (VT), and induced active expiration; in
      contrast, reducing excitation had no effect. This result is congruent with pFL
      neurons constituting a conditional expiratory oscillator comprised of a
      functionally homogeneous set of excitatory neurons that are tonically suppressed
      at rest. In the pFV, disinhibition increased f with a presumptive reflexive
      decrease in VT; excitation increased f, VT and sigh rate; reducing excitation
      decreased VT with a presumptive reflexive increase in f. Therefore, the pFV, has
      multiple functional roles that require further parcellation. Interestingly, while
      hyperpolarization of the pFV reduces ongoing expiratory activity, no perturbation
      of pFV excitability induced active expiration. Thus, while the pFV can affect
      ongoing expiratory activity, presumably generated by the pFL, it does not appear
      capable of directly inducing active expiration. We conclude that the pFL contains
      neurons that can initiate, modulate, and sustain active expiration, whereas the
      pFV contains subpopulations of neurons that differentially affect various aspects
      of breathing pattern, including but not limited to modulation of ongoing
      expiratory activity.

PMID- 30096152
TI  - scPipe: A flexible R/Bioconductor preprocessing pipeline for single-cell RNA
      sequencing data.
AB  - Single-cell RNA sequencing (scRNA-seq) technology allows researchers to profile
      the transcriptomes of thousands of cells simultaneously. Protocols that
      incorporate both designed and random barcodes have greatly increased the
      throughput of scRNA-seq, but give rise to a more complex data structure. There is
      a need for new tools that can handle the various barcoding strategies used by
      different protocols and exploit this information for quality assessment at the
      sample-level and provide effective visualization of these results in preparation
      for higher-level analyses. To this end, we developed scPipe, an R/Bioconductor
      package that integrates barcode demultiplexing, read alignment, UMI-aware gene
      level quantification and quality control of raw sequencing data generated by
      multiple protocols that include CEL-seq, MARS-seq, Chromium 10X, Drop-seq and
      Smart-seq. scPipe produces a count matrix that is essential for downstream
      analysis along with an HTML report that summarises data quality. These results
      can be used as input for downstream analyses including normalization,
      visualization and statistical testing. scPipe performs this processing in a few
      simple R commands, promoting reproducible analysis of single-cell data that is
      compatible with the emerging suite of open-source scRNA-seq analysis tools
      available in R/Bioconductor and beyond. The scPipe R package is available for
      download from https://www.bioconductor.org/packages/scPipe.

PMID- 30096153
TI  - Using Garden Cafes to engage community stakeholders in health research.
AB  - Science Cafes, informal venues to promote bidirectional dialog, inquiry and
      learning about science between community members, scientists, healthcare and
      service providers, hold promise as an innovative tool for healthcare researchers
      and community members to improve health outcomes, especially among populations
      with health disparities. However, the process of optimizing science cafes is
      under-studied. We describe the pilot evaluation of a series of Science Cafes,
      called Garden Cafes (n = 9), conducted from September 2015 through April 2016 in
      Olmsted County, MN and Duval County, FL to connect Mayo Clinic researchers and
      local service providers with the community. Selection of discussion topics was
      guided by a county health needs assessment, which identified community
      priorities. Before leaving the events, community participants completed a brief
      anonymous survey assessing sociodemographics and their knowledge of research
      benefits, readiness to participate as a partner in health research, and health
      and science literacy confidence. Of the 112 attendees who responded, 51% were
      female and 51% were Black. Respondents reported that participating in the event
      significantly improved (all at p<0.001) their understanding on all three
      measures. Preliminary findings suggest that Garden Cafes are an effective forum
      to increase community understanding and disposition to collaborate in health
      research, especially in members from diverse backgrounds.

PMID- 30096155
TI  - Interactions of organic acids with Campylobacter coli from swine.
AB  - Campylobacter coli is a bacterial species that is a major cause of diarrheal
      disease worldwide, and Campylobacter spp. are among the top 5 foodborne pathogens
      in the United States. During food production organic acids (OAs) are often used
      to remove bacteria from animal carcasses. The interactions of six OAs with 111 C.
      coli strains obtained from swine and retail pork chops were studied by
      determining the molar minimum inhibitory concentrations (MICMs) of the C. coli
      strains, and the pH at the MICMs. The Henderson-Hasselbalch equation was used to
      calculate the concentrations of the undissociated and dissociated OAs at the
      MICMs of the C. coli strains. The results for the 111 different C. coli strains
      obtained from different locations were treated as a single group for each OA
      since many of the C. coli strains behaved similarly to each different OA.
      Inhibition of C. coli was not dependent on pH or on the undissociated OA species,
      but C. coli inhibition correlated with the dissociated OA species. Therefore, if
      the concentration of the dissociated OAs decreases from optimum, one may then
      expect that C. coli bacteria would escape disinfection. The concentration of the
      dissociated OA should be carefully controlled in a carcass wash. We suggest
      maintaining a concentration of the dissociated acetic, butyric, citric, formic,
      lactic and propionic acids at 29, 23, 11, 35, 22 and 25 mM, respectively, when
      using a carcass wash with these OAs to remove C. coli bacteria. However, due to
      C. coli utilization of acetate, formate, lactate and propionate, these four OAs
      may not be the best choice to use for a carcass wash to remove C. coli
      contamination. Of the six OAs, citric acid was the most efficient at inhibiting
      C. coli.

PMID- 30096154
TI  - Associations between body size, nutrition and socioeconomic position in early
      life and the epigenome: A systematic review.
AB  - BACKGROUND: Body size, nutrition and socioeconomic position (SEP) in early life
      have been associated with a wide range of long-term health effects. Epigenetics
      is one possible mechanism through which these early life exposures can impact
      later life health. We conducted a systematic review examining the observational
      evidence for the impact of body size, nutrition and SEP in early life on the
      epigenome in humans. METHODS: This systematic review is registered with the
      PROSPERO database (registration number: CRD42016050193). Three datasets were
      simultaneously searched using Ovid and the resulting studies were evaluated by at
      least two independent reviewers. Studies measuring epigenetic markers either at
      the same time as, or after, the early life exposure and have a measure of body
      size, nutrition or SEP in early life (up to 12 years), written in English and
      from a community-dwelling participants were included. RESULTS: We identified 90
      eligible studies. Seventeen of these papers examined more than one early life
      exposure of interest. Fifty six papers examined body size, 37 nutrition and 17
      SEP. All of the included papers examined DNA methylation (DNAm) as the epigenetic
      marker. Overall there was no strong evidence for a consistent association between
      these early life variables in DNAm which may be due to the heterogeneous study
      designs, data collection methods and statistical analyses. CONCLUSIONS: Despite
      these inconclusive results, the hypothesis that the early life environment can
      impact DNAm, potentially persisting into adult life, was supported by some
      studies and warrants further investigation. We provide recommendations for future
      studies.

PMID- 30096156
TI  - Lifestyle and prevalence of dysmenorrhea among Spanish female university
      students.
AB  - The aim of this study was to determine the prevalence of primary dysmenorrhea in
      a sample of Spanish university students, and to describe their menstrual
      characteristics, lifestyle habits and associated risk factors. This cross
      sectional study was conducted with a total of 258 young female university
      students recruited from the Ciudad Real Faculty of Nursing, with a mean age of
      20.63+/- 3.32 years. An anonymous self-report questionnaire was used to collect
      data from students. This included sociodemographic characteristics, lifestyle
      habits, gynecological personal history and the severity of pain using the visual
      analogue scale. The statistical analysis of the data included calculation of the
      mean, percentages, chi-square analysis of the data and logistic regression. The
      prevalence of dysmenorrhea was of 74.8% (n = 193) with a mean pain severity of
      6.88 (+/-1.71). Our results show that 38.3% of students described their menstrual
      pain as severe and 58% as moderate. The bivariate analysis showed statistically
      significant differences between students with and without dysmenorrhea: a higher
      proportion of women with dysmenorrhea had a greater duration of the menstruation
      flow (p = .003), a longer duration of the menstrual cycle (p = .046), were not
      using the oral contraceptive pill (p = .026) and had a family history of
      dysmenorrhea (p = .001). Backward step-wise binary logistic regression analysis
      using all the significant bivariate variables including lifestyle variables
      revealed the following risk factors: drinking cola drinks, duration of the
      menstrual flow, eating meat and having a first-degree relative affected by
      dysmenorrhea.

PMID- 30096157
TI  - iMapSplice: Alleviating reference bias through personalized RNA-seq alignment.
AB  - Genomic variants in both coding and non-coding sequences can have functionally
      important and sometimes deleterious effects on exon splicing of gene transcripts.
      For transcriptome profiling using RNA-seq, the accurate alignment of reads across
      exon junctions is a critical step. Existing algorithms that utilize a standard
      reference genome as a template sometimes have difficulty in mapping reads that
      carry genomic variants. These problems can lead to allelic ratio biases and the
      failure to detect splice variants created by splice site polymorphisms. To
      improve RNA-seq read alignment, we have developed a novel approach called
      iMapSplice that enables personalized mRNA transcriptome profiling. The algorithm
      makes use of personal genomic information and performs an unbiased alignment
      towards genome indices carrying both reference and alternative bases.
      Importantly, this breaks the dependency on reference genome splice site
      dinucleotide motifs and enables iMapSplice to discover personal splice junctions
      created through splice site polymorphisms. We report comparative analyses using a
      number of simulated and real datasets. Besides general improvements in read
      alignment and splice junction discovery, iMapSplice greatly alleviates allelic
      ratio biases and unravels many previously uncharacterized splice junctions
      created by splice site polymorphisms, with minimal overhead in computation time
      and storage. Software download URL: https://github.com/LiuBioinfo/iMapSplice.

PMID- 30096158
TI  - Studying additive interaction in a healthcare database: Case study of NSAIDs,
      cardiovascular profiles, and acute myocardial infarction.
AB  - PURPOSE: There are clinical trial data on risk of acute myocardial infarction
      (MI) with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at increased
      cardiovascular (CV) risk requiring chronic daily treatment. This study
      investigated whether risks of acute MI with real-world prescription NSAIDs, such
      as low-dose or intermittent use, vary according to an individual's CV profile.
      METHODS: Nested case-control analyses were carried out on an administrative
      health cohort from Quebec, Canada by randomly selecting 10 controls per case
      matched on age +/- 1 year, sex, and month and year of cohort entry. We measured
      the additive joint effects on acute MI of current NSAID use and presence of
      hypertension, coronary heart disease (CHD), history of previous MI, or
      concomitant use of cardioprotective aspirin. The endpoint was the relative excess
      risk due to interaction (RERI). To verify the robustness of interaction findings,
      we performed sensitivity analyses with varying specifications of NSAID exposure
      related variables. RESULTS: The cohort consisted of 233 816 elderly individuals,
      including 21 256 acute MI cases. For hypertension, CHD, and previous MI, we
      identified additive interactions on MI risk with some but not all NSAIDs, which
      also depended on the definition of NSAID exposure. Hypertension was sub-additive
      with naproxen but not with the other NSAIDs. Celecoxib and CHD were sub-additive
      in the primary analysis only (modelling NSAID dose on index date or up to 7 days
      before-best-fitting base model) whereas celecoxib and rofecoxib were super
      additive with a history of previous MI in the secondary analysis only (modelling
      NSAID use on index date). For cardioprotective aspirin we found no evidence for
      an additive interaction with any of the NSAIDs. CONCLUSIONS: Alternative
      specifications of NSAID exposure concurred in finding that concomitant use of
      cardioprotective aspirin does not attenuate the risks of acute MI with NSAIDs.
      However we were unable to demonstrate consistent interactions between an
      individual's cardiovascular comorbidities and NSAID-associated acute MI. Our
      study highlights challenges of studying additive interactions in a healthcare
      database and underscores the need for sensitivity analyses.

PMID- 30096159
TI  - Connections and containers: Using genetic data to understand how watershed
      evolution and human activities influence cutthroat trout biogeography.
AB  - Species with large geographic distributions often exhibit complex patterns of
      diversity that can be further complicated by human activities. Cutthroat trout
      (Oncorhynchus clarkii) are one of the most widely distributed freshwater fish
      species in western North America exhibiting substantial phenotypic and genetic
      variability; however, fish stocking practices have translocated populations
      outside of their native range and may have obscured intraspecific boundaries.
      This study focuses on cutthroat trout populations representing three distinct
      evolutionary clades that are found intermixed within a contact zone between the
      Bonneville and upper Snake River watersheds in the western United States. We used
      mitochondrial and microsatellite genetic data, as well as historical stocking
      records, to evaluate whether populations of cutthroat trout in the contact zone
      are native or are introduced. We found significant genetic differentiation and
      fine-scale genetic population structure that was organized primarily by watershed
      boundaries. While we detected increased genetic diversity in some areas in close
      proximity to the greatest number of stocking events, the highly organized
      population structure both within and between areas of the contact zone indicates
      that the populations are native to the watersheds. Intermixing of distinct
      evolutionary lineages of cutthroat trout appears to be the result of historical
      connections between paleodrainages. Our analyses provide a context for
      understanding how genetic data can be used to assess the status of populations as
      native or introduced.

PMID- 30096160
TI  - Factors associated with severe neurologic complications in patients with either
      hand-foot-mouth disease or herpangina: A nationwide observational study in South
      Korea, 2009-2014.
AB  - BACKGROUND: In 2009, a nationwide sentinel surveillance for hand-foot-mouth
      disease (HFMD) and herpangina (HA) with neurologic complications was initiated in
      South Korea. We used this surveillance system to investigate the clinical
      characteristics of patients with either HFMD or HA with neurologic complications,
      with the aim of determining risk factors for severe neurologic complications.
      METHODS: A retrospective review of medical records was conducted on all cases of
      HFMD and HA with neurologic complications that were reported in the national
      system between April 1, 2009 and December 31, 2014. A severe case was defined as
      having HFMD or HA with encephalitis, polio-like syndrome, or cardiopulmonary
      failure, and less-severe cases were defined as having HFMD or HA with aseptic
      meningitis. RESULTS: A total of 138 cases (less-severe: 90/138, 65.2%; severe:
      48/138, 24.8%) were included from 28 hospitals; 28 ineligible cases were
      excluded. Of 48 severe cases, 27 (56.2%) had encephalitis; 14 (29.2%) had polio
      like syndrome; and seven (14.6%) had cardiopulmonary syndrome. The median patient
      age was 36 months (IQR: 18-60) and 63 (45.7%) patients were female. Most patients
      completely recovered, except for seven cases that were fatal or resulted in long
      term symptoms (5.1%, 3 patients with neurologic sequelae and 4 deaths). In a
      multivariable logistic regression analysis, lethargy (OR = 4.67, 95% CI: 1.37
      15.96, P = 0.014), female sex (OR = 3.51, 95% CI: 1.17-10.50, P = 0.025), and
      enterovirus A71 (OR = 3.55, 95% CI: 1.09-11.57, P = 0.035) were significantly
      associated with severe neurologic complications in HFMD and HA patients.
      CONCLUSION: In patients with HFMD and HA, lethargy, female, and enterovirus A71
      may predict severe neurologic complications.

PMID- 30096161
TI  - Characterization of Drosophila ATPsynC mutants as a new model of mitochondrial
      ATP synthase disorders.
AB  - Mitochondrial disorders associated with genetic defects of the ATP synthase are
      among the most deleterious diseases of the neuromuscular system that primarily
      manifest in newborns. Nevertheless, the number of established animal models for
      the elucidation of the molecular mechanisms behind such pathologies is limited.
      In this paper, we target the Drosophila melanogaster gene encoding for the ATP
      synthase subunit c, ATPsynC, in order to create a fruit fly model for
      investigating defects in mitochondrial bioenergetics and to better understand the
      comprehensive pathological spectrum associated with mitochondrial ATP synthase
      dysfunctions. Using P-element and EMS mutagenesis, we isolated a set of mutations
      showing a wide range of effects, from larval lethality to complex pleiotropic
      phenotypes encompassing developmental delay, early adult lethality, hypoactivity,
      sterility, hypofertility, aberrant male courtship behavior, locomotor defects and
      aberrant gonadogenesis. ATPsynC mutations impair ATP synthesis and mitochondrial
      morphology, and represent a powerful toolkit for the screening of genetic
      modifiers that can lead to potential therapeutic solutions. Furthermore, the
      molecular characterization of ATPsynC mutations allowed us to better understand
      the genetics of the ATPsynC locus and to define three broad pathological
      consequences of mutations affecting the mitochondrial ATP synthase functionality
      in Drosophila: i) pre-adult lethality; ii) multi-trait pathology accompanied by
      early adult lethality; iii) multi-trait adult pathology. We finally predict
      plausible parallelisms with genetic defects of mitochondrial ATP synthase in
      humans.

PMID- 30096162
TI  - Cross sectional study of chronic hepatitis B prevalence among healthcare workers
      in an urban setting, Sierra Leone.
AB  - INTRODUCTION: Hepatitis B is a serious public health problem across sub-Saharan
      Africa. Sierra Leone has no national hepatitis B strategy plan or high quality
      estimates of prevalence. Healthcare workers are perceived as an at-risk group for
      hepatitis B. We assessed the prevalence of hepatitis B among healthcare workers
      at two hospital sites in Freetown, Sierra Leone. METHODS: In October 2017,
      healthcare workers were offered voluntary testing for hepatitis B surface antigen
      (HBsAg), hepatitis B surface antibody (anti-HBs), hepatitis B core antibody (anti
      HBc), hepatitis B e antigen (HBeAg) and hepatitis B e antibody (anti-HBe) using
      rapid lateral flow assay for all samples, followed by Enzyme Immunosorbent Assay
      to confirm positive results. Participants completed a questionnaire about
      knowledge, attitudes and practices concerning hepatitis B. HBsAg positive
      participants were invited to a clinic for further assessment. RESULTS: Overall,
      447 participants were tested for hepatitis B. Most (90.6%, 405/447) participants
      were nurses, 72.3% (323/447) were female and 71.6% (320/447) were 30 years or
      older. The prevalence of chronic hepatitis B (HBsAg positivity) was 8.7% (39 /
      447, 95% CI 6.3-11.7%). There was no significant difference in prevalence by sex,
      age group, site of work or type of job. None of the 66.7% (26 / 39) of
      participants with chronic hepatitis B who attended the clinic met the 2015 WHO
      criteria to start treatment for hepatitis B on the basis of cirrhosis. Most
      participants (96.9% 432 / 446) stated that they were worried about their risk of
      hepatitis B at work. CONCLUSIONS: Hepatitis B is highly prevalent among
      healthcare workers in Sierra Leone. It is unclear whether this reflects high
      community prevalence or is due to occupational risk. No participants with chronic
      hepatitis B needed to start treatment. In order to achieve the WHO target of
      elimination of viral hepatitis by 2030, introduction of birth dose vaccine for
      infants and catch-up vaccines for healthcare workers and healthcare students,
      together with a national hepatitis B screen and treat programme is advisable for
      Sierra Leone.

PMID- 30096163
TI  - Evidence of multiple colonizations as a driver of black fly diversification in an
      oceanic island.
AB  - True oceanic islands typically host reduced species diversity together with high
      levels of endemism, which make these environmental set-ups ideal for the
      exploration of species diversification drivers. In the present study, we used
      black fly species (Diptera: Simuliidae) from Reunion Island as a model to
      highlight the main drivers of insect species diversification in this young and
      remote volcanic island located in the Southwestern Indian Ocean. Using local and
      regional (Comoros and Seychelles archipelagos) samples as well as specimens from
      continental Africa, we tested the likelihood of two distinct scenarios, i.e.
      multiple colonizations vs. in-situ diversification. For this, posterior odds were
      used to test whether species from Reunion did form a monophyletic group and we
      estimated divergence times between species. Three out of the four previously
      described Reunion black fly species could be sampled, namely Simulium ruficorne,
      Simulium borbonense and Simulium triplex. The phylogenies based on nuclear and
      mitochondrial markers showed that S. ruficorne and S. borbonense are the most
      closely related species. Interestingly, we report a probable mitochondrial
      introgression between these two species although they diverged almost six million
      years ago. Finally, we showed that the three Reunion species did not form a
      monophyletic group, and, combined with the molecular datation, the results
      indicated that Reunion black fly diversity resulted from multiple colonization
      events. Thus, multiple colonizations, rather than in-situ diversification, are
      likely responsible for an important part of black fly diversity found on this
      young Darwinian island.

PMID- 30096165
TI  - The metabolomic plasma profile of myeloma patients is considerably different from
      healthy subjects and reveals potential new therapeutic targets.
AB  - INTRODUCTION: Multiple myeloma (MM), a malignant plasma cell disorder, is still
      an incurable disease. Thus, the identification of novel therapeutic targets is of
      utmost importance. Here, we evaluated the peripheral blood-based metabolic
      profile of patients with MM. MATERIAL & METHODS: Peripheral blood plasma levels
      of 188 endogenous metabolites, including amino acids, biogenic amines,
      acylcarnitines, glycerophospholipids, sphingomyelins, and hexoses were determined
      in patients with plasma cell dyscrasias: monoclonal gammopathy of undetermined
      significance, a precursor stage of MM (MGUS, n = 15), newly diagnosed MM, (NDMM,
      n = 32), relapsed/refractory MM (RRMM, n = 19) and in 25 healthy controls by mass
      spectrometry. RESULTS: Patients with NDMM, RRMM and MGUS have a substantially
      different metabolomic profile than healthy controls. The amount of eight plasma
      metabolites significantly differs between the NDMM and MGUS group: free
      carnitine, acetylcarnitine, glutamate, asymmetric dimethylarginine (ADMA) and
      four phosphatidylcholine (PC) species. In addition, the levels of
      octadecanoylcarnitine, ADMA and six PCs were significantly different between RRMM
      and MGUS patients. 13 different concentrations of metabolites were found between
      RRMM and NDMM patients (free carnitine, acetylcarnitine, creatinine, five LysoPCs
      and PCs). Pathway analyses revealed a distinct metabolic profile with significant
      alterations in amino acid, lipid, and energy metabolism in healthy volunteers
      compared to MGUS/MM patients. CONCLUSION: We identified different metabolic
      profiles in MGUS und MM patients in comparison to healthy controls. Thus,
      different metabolic processes, potentially the immunoregulation by indoleamine
      2,3 dioxygenase-1 (IDO), which is involved in cancer development and progression
      supporting inflammatory processes in the tumor microenvironment and
      glutaminolysis, can serve as novel promising therapeutic targets in MM.

PMID- 30096166
TI  - Multiple PDE5Is use as a marker of decreased overall men's health: A real-life
      study.
AB  - Erectile dysfunction (ED) is considered a sentinel marker for poor general men's
      health status. Severe ED has been associated with poor response to
      phosphodiesterase type 5 inhibitors (PDE5Is) therapy. We sought to assess the
      association of multiple PDE5Is prescription with the overall patients' health
      status. Socio-demographic and clinical variables from 939 consecutive white
      European, heterosexual, sexually-active men seeking medical help for ED at same
      tertiary-referral academic outpatient clinic were analyzed. Health-significant
      comorbidities were scored with the Charlson Comorbidity Index (CCI). Patients
      have been stratified into naive and non-naive according to their history of
      previous prescriptions of any PDE5I. Every patient completed the International
      Index of Erectile Function (IIEF) questionnaire. Logistic regression models
      tested the association between patients' baseline characteristics (thus including
      previous PDE5Is prescriptions) and the overall health status. Overall, 328 (35%)
      patients were non-naive for PDE5Is. Of them, 172 (52%), 99 (30%), and 57 (17%)
      had been prescribed with 1, 2 or 3 different PDE5Is, respectively. Naive and non
      naive patients did not differ in terms of age, BMI, baseline ED severity;
      conversely, non-naive patients had a higher CCI score. At logistic MVA, the
      number of PDE5Is prescriptions emerged as an independent predictor of a higher
      burden of comorbidities regardless of ED severity; the higher the number of
      PDE5Is prescriptions, the higher the CCI score (OR 1.69, 2.49, and 2.90 for 1, 2
      or 3 previous PDE5Is, respectively), after accounting for age, BMI, baseline ED
      severity and cigarette smoking. More than a third of patients seeking medical
      help for ED at a single tertiary-referral center were non-naive for PDE5Is. The
      increasing number of previous prescriptions of PDE5Is emerged as a worrisome
      marker of a poorer overall men's health status regardless of ED severity.

PMID- 30096164
TI  - Small RNAs detected in exosomes derived from the MH7A synovial fibroblast cell
      line with TNF-alpha stimulation.
AB  - Rheumatoid arthritis (RA) is an autoimmune disease that causes the chronic
      inflammation of the joints. Intercellular communication containing synovial
      fibroblasts seems to play a major role in RA pathogenesis. In this study, to
      better understand intercellular communication related to RA pathogenesis, we
      identified exosomal microRNAs (miRNAs) derived from synovial fibroblasts.
      Exosomes were collected from an RA synovial fibroblast (RASF) cell line, namely,
      MH7A, with or without stimulation by tumor necrosis factor alpha (TNF-alpha). We
      used small RNA sequencing to analyze the profile of small RNAs, including miRNAs,
      in MH7A exosomes and cells. By using differential expression analysis, we
      identified four miRNAs (miR-155-5p, miR-146a-5p, miR-323a-5p, and miR-1307-3p)
      that are upregulated in exosomes with TNF-alpha stimulation. The identification
      of miR-155-5p and miR-146a-5p which have been reported in RA patients
      demonstrated the validity of our experimental model. Other two miRNAs were newly
      identified. miR-323a-5p was predicted to target the protein encoding gene CD6,
      which attenuates T-cell activation signals, and miR-1307-3p was predicted to
      target the protein encoding gene N-myc downstream-regulated gene 2 (NDRG2), which
      inhibits osteoclast-related gene expression. The results suggested that these
      miRNAs might be involved in RA pathogenesis. We hope our results will help us
      understand the role of RASF exosomes in RA pathogenesis.

PMID- 30096167
TI  - Enuresis in children and adolescents with sickle cell anaemia is more frequent
      and substantially different from the general population.
AB  - BACKGROUND: No large studies have examined the prevalence of enuresis, its
      various forms and risk factors in children with sickle cell anaemia (SCA) in Sub
      Saharan Africa using standardised definitions. We determined age and gender
      specific prevalence of enuresis and compared the nature of enuresis in children
      with and without SCA. We also identified predictors of enuresis in children with
      SCA. METHODS: Caregivers of children with SCA attending a tertiary centre
      haematology clinic in Nigeria were interviewed using a questionnaire. In
      addition, a separate questionnaire was completed for every sibling aged 5-17
      years whose haemoglobin genotype was known. Enuresis and its various forms were
      defined using the definitions of the International Children's Continence Society.
      RESULTS: The study involved 243 children with SCA and 243 controls matched for
      age and sex. The mean age of the study cohort was 9.9 (3.4). Females made up
      45.7% of the cohorts. The prevalence of enuresis was 49.4% and 29.6% in children
      with and without SCA, respectively (p = 0.009). In both groups, the prevalence of
      enuresis declined with age but remained five times higher at 25% in children with
      SCA aged 14-17 years compared with controls. Also, children with SCA and enuresis
      were older, more likely to have non-monosymptomatic enuresis and wet at least
      three nights per week than controls. Independent predictors of enuresis in
      children with SCA were a family history of enuresis and young age. CONCLUSION:
      Children with SCA had more frequent and more severe enuresis which persisted to
      late adolescence than age and sex-matched controls. These features indicate a
      subset of enuresis that is difficult to treat in the general population. Young
      age and enuresis in a family member define a subset of children with SCA more
      likely to have enuresis. Healthcare workers need to discuss enuresis with parents
      of children with SCA and offer referral to continence services.

PMID- 30096168
TI  - Identification of genomic regions associated with agronomic and biofortification
      traits in DH populations of rice.
AB  - Rice provides energy and nutrition to more than half of the world's population.
      Breeding rice varieties with the increased levels of bioavailable micronutrients
      is one of the most sustainable approaches to tackle micronutrient malnutrition.
      So, high zinc and iron content in the grain are primary targets in rice
      biofortification breeding. In this study, we conducted QTL mapping using doubled
      haploid (DH) populations, PSBRc82 x Joryeongbyeo and PSBRc82 x IR69428,
      phenotyped for agronomic traits and micronutrients during two growing seasons and
      using genotypic information from analysis with the 6K SNP chip. A number of DH
      lines were identified as having high grain Zn and Fe content in polished rice.
      Importantly, we identified 20 QTLs for agronomic traits and 59 QTLs for a number
      of biofortification traits. Of the 79 QTLs, 12 were large-effect QTLs (>25% PVE),
      nine QTLs were consistent across seasons in either population, and one QTL was
      identified in both populations. Moreover, at least two QTLs were clustered in
      defined regions of chromosomes 1, 2, 3, 4, 5, 7 and 9. Eight epistatic
      interactions were detected for Cu, Mg, Na, and Zn in population 1. Furthermore,
      we identified several candidate genes near QTLs for grain Zn (OsNRAMP, OsNAS,
      OsZIP, OsYSL, OsFER, and OsZIFL family) and grain yield (OsSPL14 and OsSPL16).
      These new QTLs and candidate genes help to further elucidate the genetic basis
      for grain micronutrient concentration, and may prove useful for marker assisted
      breeding for this important trait.

PMID- 30096169
TI  - Collecting size-selectivity data for Antarctic krill (Euphausia superba) with a
      trawl independent towing rig.
AB  - For the development of efficient trawls to minimize catch loss, escape mortality
      and potential negative ecosystem impacts from the fishery, the understanding
      about trawl selectivity processes are crucial. Small crustaceans are regarded as
      being less motile than most fish species. Crustaceans also display low levels of
      active avoidance from trawl netting, which in turn may cause direct contact with
      netting on multiple occasions on their passage towards the codend increasing the
      probability for escapement. Full-scaled experiments to estimate gear selectivity
      are highly resource demanding and are highly technically challenging for several
      types of fisheries. In this study, we developed and tested a trawl-independent
      towed-rig construction designed to investigate size selectivity of Antarctic
      krill (Euphausia superba). The results indicate that valid selectivity estimates
      can be obtained using this method, but due to the small sample size, results are
      inconclusive. However, the findings of the current study show a potential for
      developing easier and more cost-effective ways of investigating and estimating
      size selectivity of Antarctic krill and other small crustacean species in trawls.

PMID- 30096170
TI  - Toothed whale and shark depredation indicators: A case study from the Reunion
      Island and Seychelles pelagic longline fisheries.
AB  - Depredation in marine ecosystems is defined as the damage or removal of fish or
      bait from fishing gear by predators. Depredation raises concerns about the
      conservation of species involved, fisheries yield and profitability, and
      reference points based on stock assessment of depredated species. Therefore, the
      development of accurate indicators to assess the impact of depredation is needed.
      Both the Reunion Island and the Seychelles archipelago pelagic longline fisheries
      targeting swordfish (Xiphias gladius) and tuna (Thunnus spp.) are affected by
      depredation from toothed whales and pelagic sharks. In this study, we used
      fishery data collected between 2004 and 2015 to propose depredation indicators
      and to assess depredation levels in both fisheries. For both fisheries, the
      interaction rate (depredation occurrence) was significantly higher for shark
      compared to toothed whale depredation. However, when depredation occurred,
      toothed whale depredation impact was significantly higher than shark depredation
      impact, with higher depredation per unit effort (number of fish depredated per
      1000 hooks) and damage rate (proportion of fish depredated per depredated set).
      The gross depredation rate in the Seychelles was 18.3%. A slight increase of the
      gross depredation rate was observed for the Reunion Island longline fleet from
      2011 (4.1% in 2007-2010 and 4.4% in 2011-2015). Economic losses due to
      depredation were estimated by using these indicators and published official
      statistics. A loss of 0.09 EUR/hook due to depredation was estimated for the
      Reunion Island longline fleet, and 0.86 EUR/hook for the Seychelles. These
      results suggest a southward decreasing toothed whale and shark depredation
      gradient in the southwest Indian Ocean. Seychelles depredation levels are among
      the highest observed in the world revealing this area as a "hotspot" of
      interaction between pelagic longline fisheries and toothed whales. This study
      also highlights the need for a set of depredation indicators to allow for a
      global comparison of depredation rates among various fishing grounds worldwide.

PMID- 30096171
TI  - Factors influencing choice of health system access level in China: A systematic
      review.
AB  - OBJECTIVE: In China, patients increasingly choose to access already severely
      overcrowded higher level hospitals, leaving lower level facilities with low
      utilization rates. This situation undermines the effectiveness and efficiency of
      the health system. The situation tends to worsen despite policy measures aimed at
      improvement. We systematically review the factors affecting patient choice to
      synthesize scientific understanding of health system access in China. The review
      provides an evidence base for measures to direct patient flow towards lower level
      facilities. METHODS: We screened the peer-reviewed literature published from
      April 2009 to January 2016 that investigates Chinese patients' choice of health
      care facilities at different levels and assessed 45 studies in total. We applied
      two structured forms to extract data on each study's characteristics,
      methodology, and factors. RESULTS OF DATA SYNTHESIS: The results identified four
      factor types: 1) patient, 2) provider, 3) context and 4) composite: combined
      patient, provider, and/or context attributes. Patient factors are mentioned the
      most, but the evidence on patient factors is often inconclusive. Evidence
      suggests that the provider factors 'drug variety' and 'equipment', and composite
      factor 'perceived quality', push patients from lower levels towards higher
      levels. CONCLUSION: Underuse of primary care facilities and overcrowding of
      higher level facilities will likely be amplified by current demographic trends.
      Evidence suggests that improving drug availability, equipment and perceived
      quality of primary care services can improve the situation. Well-designed
      research that considers the interactions between factors is called for to better
      inform future interventions.

PMID- 30096172
TI  - LSD1 mediated changes in the local redox environment during the DNA damage
      response.
AB  - The redox state of the cell can be affected by many cellular conditions. In this
      study we show that detectable reactive oxygen species (ROS) are also generated in
      response to DNA damage by the chromatin remodeling factor and monoamine oxidase
      LSD1/KDM1A. This raised the possibility that the localized generation of hydrogen
      peroxide produced by LSD1 may affect the function of proximally located DNA
      repair proteins. The two major pathways for repair of DNA double-strand breaks
      (DSBs) are homologous recombination (HR) and non-homologous end joining (NHEJ).
      Cells were exposed to low levels of ectopic H2O2, DNA breaks generated by laser
      light, and recruitment kinetics of NHEJ protein Ku80 to DNA damage sites
      determined. Ku80 recruitment to damage sites was significantly decreased in cells
      pretreated with H2O2 while HR end binding protein Nbs1 was increased. This
      suggests that the DNA repair pathway choice has the potential to be modulated by
      the local redox state. This has implications for chemotherapeutic approaches
      involving generating DNA damage to target actively dividing cancer cells, which
      may be more or less effective dependent on the redox state of the targeted cells
      and the predominant repair pathway required to repair the type of DNA damage
      generated.

PMID- 30096173
TI  - Is pornography use a risk for adolescent well-being? An examination of temporal
      relationships in two independent panel samples.
AB  - Cross-sectional evidence suggests that pornography use is related to lower mental
      well-being among adolescents but it remains unclear if changes in well-being are
      related to the dynamics of pornography use within this population. We examined
      the relationship between pornography use, subjective well-being, symptoms of
      depressions and anxiety, and self-esteem in two independent panel samples (N =
      455; N = 858) of Croatian adolescents using cross-lagged path analysis and lagged
      linear mixed models. After controlling for impulsiveness and family environment
      factors that are unlikely to be influenced by pornography use-earlier levels of
      pornography use were not significantly associated with subsequent decreases in
      subjective well-being across gender and panel. However, pornography use was
      associated with increases in both self-esteem and symptoms of depression and
      anxiety, albeit only among adolescent women in one of the two panels. In
      addition, low subjective well-being was associated with a subsequent increase in
      pornography use, but only in female adolescents in one panel. This study's
      results are not consistent with concerns about pornography use negatively
      contributing to male adolescents' psychological well-being, but suggest potential
      antagonistic links between pornography use and specific facets of mental well
      being in adolescent women. Such links should be considered tentative until
      verified with further research.

PMID- 30096174
TI  - The implementation of Xpert MTB/RIF assay for diagnosis of tuberculosis in Nepal:
      A mixed-methods analysis.
AB  - BACKGROUND: Tuberculosis (TB) is a major public health problem in low and middle
      income countries. Early detection and enrolment of TB cases is a challenge for
      National TB Programs. OBJECTIVE: To understand the performance and feasibility
      for scale-up of Xpert MTB/RIF assay for the TB diagnosis in Nepal. DESIGN:
      Implementation research employed mixed-method sequential explanatory design. The
      results of Xpert MTB/RIF assay were analysed in 26 TB diagnostic centres where
      Xpert machines had been installed before 2015. In-depth interviews and focus
      group discussions were conducted with stakeholders, purposively selected to
      represent experiences in centres that were functioning well, poorly or not
      functioning. RESULTS: During a one-year period in 2015/16, 23,075 Xpert MTB/RIF
      assays were performed in 21 diagnostic centres with 22,288 people also tested by
      sputum microscopy. Among these, 77% had concordant (positive or negative)
      results, demonstrating fair agreement (Kappa score, 0.3) between test results.
      Test failure and positivity rates in diagnostic centres ranged from 2.6% to 13.4%
      and 6.5% to 49%, respectively. The number of cartridges per positive result
      varied from 2.3 to 10.2. Xpert assay was positive in 3314 (15% of all cases)
      sputum smear microscopy negative cases. Of 4280 bacteriologically confirmed cases
      by Xpert assay, 355 (8%) were rifampicin resistant. Xpert machines were no longer
      functioning regularly throughout the year in 5 diagnostic centres. The main
      barriers for effective implementation of Xpert in Nepal were the lack of: timely
      supply of cartridges; replacement of damaged modules; maintenance of Xpert
      machines; and stock verification for timely procurement of cartridges. Inadequate
      laboratory infrastructure for maintaining functional Xpert equipment further
      challenges implementation and scale-up. CONCLUSION: The implementation of Xpert
      MTB/RIF assay has increased case-finding of TB and MDR-TB in Nepal. However,
      there is a need to improve laboratory performance and strengthen laboratory
      infrastructure for optimal utilisation and scale-up of Xpert.

PMID- 30096175
TI  - Contribution of excision repair cross-complementing group 1 genotypes to triple
      negative breast cancer risk.
AB  - Compared with other subgroups of breast cancer, triple negative breast cancer
      (TNBC) is considered to be the one with the greatest invasiveness and metastatic
      mobility, and the highest recurrence rate. Considering the lack of predictive
      markers for TNBC, we aimed to examine the contribution of excision repair cross
      complementing-group 1 (ERCC1) genotypes to TNBC. The rs11615 and rs3212986 of
      ERCC1 were investigated and evaluated for their associations with susceptibility
      to breast cancer, especially TNBC, in Taiwan. In this study, 1,232 breast cancer
      patients (104 were TNBC) and 1,232 healthy controls were recruited and their
      genotypes at ERCC1 rs11615 and rs3212986 were revealed by polymerase chain
      reaction restriction fragment length polymorphism (PCR-RFLP) analysis. Our
      results indicated that genotypes of ERCC1 rs11615 (Ptrend = 2.2*10E-9), but not
      rs3212986 (Ptrend = 0.6181), were associated with breast cancer risk. In the
      allelic frequency distribution analysis, breast cancer patients carried the T
      allele of ERCC1 rs11615 a higher rate than the control subjects, further
      supporting the idea that ERCC1 rs11615 TT genotype is positively associated with
      breast cancer susceptibility. More importantly, the frequency of the ERCC1
      rs11615 TT genotype was even higher among TNBC patients than among other subtypes
      of breast cancer patients (P = 0.0001, odds ratio = 1.73, 95% confidence interval
      = 1.15-2.63). The genotypes of ERCC1 rs11615 were not associated with Ki67
      status. Our findings firstly show that the T allele of ERCC1 rs11615 can serve as
      a predictive biomarker for breast cancer and TNBC. We believe that ERCC1 could
      serve as a target for personalized treatment of breast cancer, especially for
      TNBC.

PMID- 30096177
TI  - Incremental treatment costs for HIV-infected women initiating antiretroviral
      therapy during pregnancy: A 24-month micro-costing cohort study for a maternal
      and child health clinic in Kenya.
AB  - BACKGROUND: To date, little information exists on the costs of providing
      antiretroviral therapy (ART) within maternal and child health (MCH) clinics in
      Kenya. The main objective of this analysis was to estimate the annual incremental
      cost of providing ART within a MCH clinic for adult women initiated on ART during
      pregnancy over the first one and two years on treatment. The study site was the
      District Hospital in Kericho, Kenya. METHODS: A micro-costing approach from the
      provider's perspective, based on a retrospective review of patient medical
      records, was used to evaluate incremental costs of care (2012 USD). Cost per
      patient in two cohorts were evaluated: the MCH clinic group comprised of adult
      women who initiated ART at the site's MCH clinic during pregnancy between 2008
      2011; and for comparison, the ART clinic group comprised of adult, non-pregnant
      women who initiated ART at the site's ART clinic during 2008-2011. The two groups
      were matched on age and baseline CD4 count at initiation. Retention at year
      one/two on ART was defined as having completed a clinic visit at 365/730 days on
      ART +/- 90 days. RESULTS: For patients defined as retained in care at year one,
      average incremental costs per patient were $234 for the MCH clinic group (median:
      215; IQR: 186, 282) and $292 in the ART clinic group (median: 227; IQR: 178,
      357). ARV and laboratory costs were less on average for the MCH clinic group
      compared to the ART clinic group (due to lower cost regimens and fewer tests),
      while personnel costs were higher for the MCH clinic group. CONCLUSIONS: The
      annual incremental cost per patient of providing ART were similar in the two
      clinic settings in 2012. With shifts in recommended ARV regimens and lab
      monitoring over time, annual costs of care (using 2016 USD unit costs) have
      remained relatively constant in nominal terms for the MCH clinic group but have
      fallen substantially for the ART clinic group (from nominal $292 in 2012 to
      nominal $227 in 2016).

PMID- 30096176
TI  - BioPS: System for screening and assessment of biofuel-production potential of
      cyanobacteria.
AB  - BACKGROUND: Cyanobacteria are one of the target groups of organisms explored for
      production of free fatty acids (FFAs) as biofuel precursors. Experimental
      evaluation of cyanobacterial potential for FFA production is costly and time
      consuming. Thus, computational approaches for comparing and ranking
      cyanobacterial strains for their potential to produce biofuel based on the
      characteristics of their predicted proteomes can be of great importance. RESULTS:
      To enable such comparison and ranking, and to assist biotechnology developers and
      researchers in selecting strains more likely to be successfully engineered for
      the FFA production, we developed the Biofuel Producer Screen (BioPS) platform
      (http://www.cbrc.kaust.edu.sa/biops). BioPS relies on the estimation of the
      predicted proteome makeup of cyanobacterial strains to produce and secrete FFAs,
      based on the analysis of well-studied cyanobacterial strains with known FFA
      production profiles. The system links results back to various external
      repositories such as KEGG, UniProt and GOLD, making it easier for users to
      explore additional related information. CONCLUSION: To our knowledge, BioPS is
      the first tool that screens and evaluates cyanobacterial strains for their
      potential to produce and secrete FFAs based on strain's predicted proteome
      characteristics, and rank strains based on that assessment. We believe that the
      availability of such a platform (comprising both a prediction tool and a
      repository of pre-evaluated stains) would be of interest to biofuel researchers.
      The BioPS system will be updated annually with information obtained from newly
      sequenced cyanobacterial genomes as they become available, as well as with new
      genes that impact FFA production or secretion.

PMID- 30096178
TI  - Ethnic bias amongst medical students in Aotearoa/New Zealand: Findings from the
      Bias and Decision Making in Medicine (BDMM) study.
AB  - Although health provider racial/ethnic bias has the potential to influence health
      outcomes and inequities, research within health education and training contexts
      remains limited. This paper reports findings from an anonymous web-based study
      examining racial/ethnic bias amongst final year medical students in Aotearoa/New
      Zealand. Data from 302 students (34% of all eligible final year medical students)
      were collected in two waves in 2014 and 2015 as part of the Bias and Decision
      Making in Medicine (BDMM) study. Two chronic disease vignettes, two implicit bias
      measures, and measures of explicit bias were used to assess racial/ethnic bias
      towards New Zealand European and Maori (indigenous) peoples. Medical students
      demonstrated implicit pro-New Zealand European racial/ethnic bias on average, and
      bias towards viewing New Zealand European patients as more compliant relative to
      Maori. Explicit pro-New Zealand European racial/ethnic bias was less evident, but
      apparent for measures of ethnic preference, relative warmth, and beliefs about
      the compliance and competence of Maori patients relative to New Zealand European
      patients. In addition, racial/ethnic bias appeared to be associated with some
      measures of medical student beliefs about individual patients by ethnicity when
      responding to a mental health vignette. Patterning of racial/ethnic bias by
      student characteristics was not consistent, with the exception of some
      associations between student ethnicity, socioeconomic background, and
      racial/ethnic bias. This is the first study of its kind with a health
      professional population in Aotearoa/New Zealand, representing an important
      contribution to further understanding and addressing current health inequities
      between Maori and New Zealand European populations.

PMID- 30096180
TI  - Biodiversity thresholds in invertebrate communities: The responses of dung beetle
      subgroups to forest loss.
AB  - Extinction thresholds have been predicted to be critical values of habitat loss
      in which an abrupt reduction in populations occurs through the interaction
      between reduced habitat and increased isolation in the landscape. In communities,
      extinction thresholds are referred to as 'biodiversity thresholds'. The
      biodiversity threshold values documented so far occur between 30% and 50% of
      habitat cover in landscapes. However, the assessment of biodiversity thresholds
      has mainly focused on vertebrate and plant communities. Here, we evaluated the
      occurrence of biodiversity thresholds in dung beetle communities by sampling ten
      3,600 ha Atlantic Forest landscapes with forest cover ranging from 5% to 55%. We
      analysed the response patterns (abundance, gamma and mean alpha diversity) of
      community subgroups with different levels of forest dependency (forest species,
      generalist species, and open-area species) using model selection, comparing null,
      linear, bell-shaped and logistic models. The response of the community of forest
      species equally fits both linear and logistic models predicting a biodiversity
      threshold at 25% forest cover. Generalist species showed peak abundance at 20%
      forest cover although this result reflects a very poor generalist assembly. Open
      area specialists did not respond to the amount of forest. The two most plausible
      models for forest species suggest two different biodiversity management options.
      Since the biodiversity threshold model represents a more dramatic scenario for
      the loss of biodiversity in Atlantic forest landscapes, we suggest, based on
      precautionary principle, that our results should strength guidelines that
      consider minimum values of forest cover in management strategies to avoid abrupt
      biodiversity loss and impacts on ecosystem services.

PMID- 30096181
TI  - Spodoptera littoralis oral secretions inhibit the activity of Phaseolus lunatus
      plasma membrane H+-ATPase.
AB  - Biotic stresses induced by herbivores result in diverse physiological changes in
      plants. In the interaction between the Lima bean (Phaseolus lunatus) and the
      herbivore Spodoptera littoralis, the earliest event induced by feeding on leaves
      is the depolarization of the plasma membrane potential (Vm), which is the results
      of both mechanical damage and insect oral secretions (OS). Although this
      herbivore-induced Vm depolarization depends on a calcium-dependent opening of
      potassium channels, the attacked leaf remains depolarized for an extended period,
      which cannot be explained by the sole action of potassium channels. Here we show
      that the plasma membrane H+-ATPase of P. lunatus leaves is strongly inhibited by
      S. littoralis OS. Inhibition of the H+-ATPase was also found in plasma membranes
      purified from leaf sections located distally from the application zone of OS,
      thus suggesting a long-distance transport of a signaling molecule(s). S.
      littoralis' OS did not influence the amount of the plasma membrane H+-ATPase,
      whereas the levels of membrane-bound 14-3-3 proteins were significantly decreased
      in membranes purified from treated leaves. Furthermore, OS strongly reduced the
      in vitro interaction between P. lunatus H+-ATPase and 14-3-3 proteins. The
      results of this work demonstrate that inhibition of the plasma membrane H+-ATPase
      is a key component of the S. littoralis OS mechanism leading to an enduring Vm
      depolarization in P. lunatus wounded leaves.

PMID- 30096182
TI  - Correction: A rapid multiplex PCR assay for presumptive species identification of
      rhinoceros horns and its implementation in Vietnam.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198565.].

PMID- 30096179
TI  - Modeling subjective relevance in schizophrenia and its relation to aberrant
      salience.
AB  - In schizophrenia, increased aberrant salience to irrelevant events and reduced
      learning of relevant information may relate to an underlying deficit in relevance
      detection. So far, subjective estimates of relevance have not been probed in
      schizophrenia patients. The mechanisms underlying belief formation about
      relevance and their translation into decisions are unclear. Using novel
      computational methods, we investigated relevance detection during implicit
      learning in 42 schizophrenia patients and 42 healthy individuals. Participants
      underwent functional magnetic resonance imaging while detecting the outcomes in a
      learning task. These were preceded by cues differing in color and shape, which
      were either relevant or irrelevant for outcome prediction. We provided a novel
      definition of relevance based on Bayesian precision and modeled reaction times as
      a function of relevance weighted unsigned prediction errors (UPE). For aberrant
      salience, we assessed responses to subjectively irrelevant cue manifestations.
      Participants learned the contingencies and slowed down their responses following
      unexpected events. Model selection revealed that individuals inferred the
      relevance of cue features and used it for behavioral adaption to the relevant cue
      feature. Relevance weighted UPEs correlated with dorsal anterior cingulate cortex
      activation and hippocampus deactivation. In patients, the aberrant salience bias
      to subjectively task-irrelevant information was increased and correlated with
      decreased striatal UPE activation and increased negative symptoms. This study
      shows that relevance estimates based on Bayesian precision can be inferred from
      observed behavior. This underscores the importance of relevance detection as an
      underlying mechanism for behavioral adaptation in complex environments and
      enhances the understanding of aberrant salience in schizophrenia.

PMID- 30096184
TI  - High school science fair: Student opinions regarding whether participation should
      be required or optional and why.
AB  - The goal of our research is to identify strengths and weaknesses of high school
      level science fair and improvements that might enhance learning outcomes based on
      empirical assessment of student experiences. We use the web-based data collection
      program REDCap to implement anonymous and voluntary surveys about science fair
      experiences with two independent groups-high school students who recently
      competed in the Dallas Regional Science and Engineering Fair and post high school
      students (undergraduates, 1st year medical students, and 1st year biomedical
      graduate students) on STEM education tracks doing research at UT Southwestern
      Medical Center. Herein, we report quantitative and qualitative data showing
      student opinions about the value of science fair. Few students in any group
      thought that competitive science fair (C-SF) should be required. The most common
      reasons given for not requiring C-SF were no enjoyment and no interest in
      competing. On the other hand, student attitudes towards requiring non-competitive
      science fair (NC-SF) were nuanced and ranged as high as 91%, increasing with
      student maturation, science fair experience, and STEM track. The most common
      reasons given for requiring NC-SF were learning scientific thinking skills and
      research skills. Students opposed to requiring NC-SF most frequently mentioned no
      enjoyment and no interest in science. Several student comments critical of the
      fairness of science fair led us to determine possible differences in science fair
      experiences depending on whether or not students received help from scientists.
      Those who received help from scientists had an easier time getting their research
      idea, more access to articles in books and magazines, and less difficulty getting
      resources. We discuss the idea that two different types of science fairs
      competitive science fair with a performance goal orientation and non-competitive
      science fair with a mastery goal orientation-might be required to promote the
      broad goal of educating all students about science and engineering.

PMID- 30096183
TI  - Discerning evolutionary trends in post-translational modification and the effect
      of intrinsic disorder: Analysis of methylation, acetylation and ubiquitination
      sites in human proteins.
AB  - Intrinsically disordered regions (IDRs) of proteins play significant biological
      functional roles despite lacking a well-defined 3D structure. For example, IDRs
      provide efficient housing for large numbers of post-translational modification
      (PTM) sites in eukaryotic proteins. Here, we study the distribution of more than
      15,000 experimentally determined human methylation, acetylation and
      ubiquitination sites (collectively termed 'MAU' sites) in ordered and disordered
      regions, and analyse their conservation across 380 eukaryotic species.
      Conservation signals for the maintenance and novel emergence of MAU sites are
      examined at 11 evolutionary levels from the whole eukaryotic domain down to the
      ape superfamily, in both ordered and disordered regions. We discover that MAU PTM
      is a major driver of conservation for arginines and lysines in both ordered and
      disordered regions, across the 11 levels, most significantly across the mammalian
      clade. Conservation of human methylatable arginines is very strongly favoured for
      ordered regions rather than for disordered, whereas methylatable lysines are
      conserved in either set of regions, and conservation of acetylatable and
      ubiquitinatable lysines is favoured in disordered over ordered. Notably, we find
      evidence for the emergence of new lysine MAU sites in disordered regions of
      proteins in deuterostomes and mammals, and in ordered regions after the dawn of
      eutherians. For histones specifically, MAU sites demonstrate an idiosyncratic
      significant conservation pattern that is evident since the last common ancestor
      of mammals. Similarly, folding-on-binding (FB) regions are highly enriched for
      MAU sites relative to either ordered or disordered regions, with ubiquitination
      sites in FBs being highly conserved at all evolutionary levels back as far as
      mammals. This investigation clearly demonstrates the complex patterns of PTM
      evolution across the human proteome and that it is necessary to consider
      conservation of sequence features at multiple evolutionary levels in order not to
      get an incomplete or misleading picture.

PMID- 30096185
TI  - Comparative mechanics of diverse mammalian carotid arteries.
AB  - The prevalence of diverse animal models as surrogates for human vascular
      pathologies necessitate a comprehensive understanding of the differences that
      exist between species. Comparative passive mechanics are presented here for the
      common carotid arteries taken from bovine, porcine, ovine, leporine, murine-rat,
      and murine-mouse specimens. Data is generated using a scalable biaxial mechanical
      testing device following consistent circumferential (pressure-diameter) and axial
      (force-length) testing protocols. The structural mechanical response of carotids
      under equivalent loading, quantified by the deformed inner radius, deformed wall
      thickness, lumen area compliance and axial force, varies significantly among
      species but generally follows allometric scaling. Conversely, descriptors of the
      local mechanical response within the deformed arterial wall, including mean
      circumferential stress, mid-wall circumferential stretch, and mean axial stress,
      are relatively consistent across species. Unlike the larger animals studied, the
      diameter distensibility curves of murine specimens are non-monotonic and have a
      significantly higher value at 100 mmHg. Taken together, our results provide
      baseline structural and mechanical information for carotid arteries across a
      broad range of common animal models.

PMID- 30096186
TI  - Cholesterol-pyrene as a probe for cholesterol distribution on ordered and
      disordered membranes: Determination of spectral wavelengths.
AB  - Biological membranes contain a large variety of lipids species compartmentalized
      in different domains heterogeneous in size, composition and dynamics. Cholesterol
      induces membrane ordered domains thanks to its affinity for saturated lipids.
      Membrane domains had been studied with fluorescent probes either linked to
      phospholipids and proteins or as individual fluorophore. However, no efficient
      formulation of a cholesterol probe has been available so far. Herein, we
      described a cholesterol-pyrene probe behaviour in heterogeneous membranes. We
      characterised the pyrene fluorescence spectra in liquid-ordered (Lo) and liquid
      disordered (Ld) membranes. Using statistical multivariate analysis, we found out
      the most appropriate wavelengths for membrane domains studies. 373 nm and 379 nm
      were the most discriminant wavelengths to follow the liquid-ordered and the
      liquid-disordered environments. Cholesterol clustering behaviour was quantified
      by the modulation of the cholesterol-pyrene excimers peak (474 nm). In liquid
      ordered membranes at low temperature, cholesterol-pyrene was found as multimers
      and as monomers. At high temperature, the liquid-ordered status of the membrane
      decreases and cholesterol-pyrene tends to cluster. In liquid-disordered
      membranes, cholesterol-pyrene was present mostly as monomers and the small
      quantity of excimers increased with temperature. Cholesterol-pyrene was used to
      test the ceramide effect on membranes, and presented a behaviour in agreement
      with the cholesterol behaviour reported in the literature. Overall, the presented
      data show that cholesterol-pyrene is an efficient sensor to study liquid ordered
      and liquid disordered organisation in membranes.

PMID- 30096187
TI  - Characterization of the glycerol-3-phosphate acyltransferase gene and its real
      time expression under cold stress in Paeonia lactiflora Pall.
AB  - Elucidating the cold tolerance mechanism of Paeonia lactiflora, which is one of
      the most valuable ornamental and medicinal plants in Asia, fundamentally impacts
      its breeding and production. The glycerol-3-phosphate acyltransferase (GPAT) gene
      plays a pivotal role in cold resistance in a variety of plant species. Here, we
      cloned the P. lactiflora GPAT gene, determined its expression pattern, and tested
      its role in cold resistance. We obtained the full-length P. lactiflora GPAT gene
      using tissue-cultured seedlings and real-time polymerase chain reaction and rapid
      amplification of cDNA ends analyses. We named this gene PlGPAT in P. lactiflora.
      Phylogenetic analysis indicates that the PlGPAT gene is closely related with the
      GPAT genes in core eudicots. The phylogenetic tree containing 31 angiosperm
      species based on GPAT protein sequences is largely consistent with the known
      phylogeny in flowering plants. We conducted a time-course PlGPAT expression
      analysis and demonstrated that PlGPAT expression is correlated with low
      temperature stress. Our results suggest that the PlGPAT gene plays an important
      role in regulating cold resistance in P. lactiflora.

PMID- 30096189
TI  - Factors influencing plagiarism in higher education: A comparison of German and
      Slovene students.
AB  - Over the past decades, plagiarism has been classified as a multi-layer phenomenon
      of dishonesty that occurs in higher education. A number of research papers have
      identified a host of factors such as gender, socialisation, efficiency gain,
      motivation for study, methodological uncertainties or easy access to electronic
      information via the Internet and new technologies, as reasons driving plagiarism.
      The paper at hand examines whether such factors are still effective and if there
      are any differences between German and Slovene students' factors influencing
      plagiarism. A quantitative paper-and-pencil survey was carried out in Germany and
      Slovenia in 2017/2018 academic year, with a sample of 485 students from higher
      education institutions. The major findings of this research reveal that easy
      access to information-communication technologies and the Web is the main reason
      driving plagiarism. In that regard, there are no significant differences between
      German and Slovene students in terms of personal factors such as gender,
      motivation for study, and socialisation. In this sense, digitalisation and the
      Web outrank national borders.

PMID- 30096188
TI  - Effect of far ultraviolet light emitted from an optical diffuser on methicillin
      resistant Staphylococcus aureus in vitro.
AB  - Drug-resistant bacteria such as methicillin-resistant Staphylococcus aureus
      (MRSA) are a target for new antimicrobial technologies. Far-UVC technology is an
      emerging disinfection method that directly kills microorganisms using light. In
      contrast with conventional UV sterilization, far-UVC light has antimicrobial
      capabilities without apparent harm to mammalian cells. This study examines the
      application of 224 nm far-UVC light delivered from a laser using an optical
      diffuser towards the goal of protecting against bacterial invasion around skin
      penetrating devices. Delivery of far-UVC using a laser and optical fibers enables
      exposure to unique geometries that would otherwise be shielded when using a lamp.
      Testing of the bactericidal potential of diffusing the far-UVC laser output over
      a large area was tested and yielded qualitative area killing results. The killing
      of MRSA using this method was also examined using an in vitro survival assay.
      Results followed a classic log-linear disinfection model with a rate constant of
      k = 0.51 cm2/mJ, which corresponds to an inactivation cross section of D90 = 4.5
      mJ/cm2. This study establishes far-UVC delivered from a laser through an optical
      diffuser as a viable solution for disinfection of susceptible regions such as
      around catheters, drivelines, or other skin penetrating medical devices.

PMID- 30096190
TI  - Persistently elevated soluble MHC class I polypeptide-related sequence A and
      transforming growth factor-beta1 levels are poor prognostic factors in head and
      neck squamous cell carcinoma after definitive chemoradiotherapy.
AB  - We evaluated the prognostic significance of immunologic inhibitory biomarkers in
      head and neck squamous cell carcinoma (HNSCC) patients undergoing definitive
      chemoradiotherapy (CRT). Thirty patients were prospectively enrolled. Plasma
      levels of soluble MHC class I polypeptide-related sequence A (sMICA) and
      transforming growth factor-beta1 (TGF-beta1) were measured before and 2 weeks
      after CRT. The median follow-up was 32.9 months (range: 12.4-40.6 months). The
      pre-treatment sMICA (p < 0.001) and TGF-beta1 (p < 0.001) levels were
      significantly increased in HNSCC patients, compared to healthy controls. In HNSCC
      patients, the median pre-CRT and post-CRT sMICA levels were 43.1 pg/mL and 65.3
      pg/mL, respectively, while the median pre-CRT and post-CRT TGF-beta1 levels were
      57.7 ng/mL and 36.0 ng/mL, respectively. After CRT, 19 patients (63.3%) exhibited
      persistently elevated sMICA, six patients (20.0%) exhibited persistently elevated
      TGF-beta1, and five patients (16.7%) exhibited persistently elevated sMICA and
      TGF-beta1. Patients with persistently elevated sMICA and TGF-beta1 after CRT
      experienced an earlier tumor progression (p = 0.030), and poor overall survival
      (p = 0.010). Our results suggest that HNSCC patients who exhibit persistently
      elevated sMICA and TGF-beta1 levels after CRT are at higher risk of tumor
      progression or death.

PMID- 30096192
TI  - Correlates of sedentary behavior in the general population: A cross-sectional
      study using nationally representative data from six low- and middle-income
      countries.
AB  - BACKGROUND: Sedentary behavior (SB) is associated with adverse health outcomes
      independent of levels of physical activity. However, data on its correlates are
      scarce from low- and middle-income countries (LMICs). Thus, we assessed the
      correlates of SB in six LMICs (China, Ghana, India, Mexico, Russia, South Africa)
      using nationally representative data. METHODS: Cross-sectional, community-based
      data on 42,469 individuals aged >=18 years from the World Health Organization's
      Study on Global Ageing and Adult Health were analyzed. Self-reported time spent
      sedentary per day was the outcome. High SB was defined as >=8 hours of SB per
      day. The correlates (sociodemographic and health-related) of high SB were
      estimated by multivariable logistic regression analyses. RESULTS: The overall
      prevalence (95%CI) of high SB was 8.3% (7.1-9.7%). In the overall sample, the
      most important sociodemographic correlates of high SB were unemployment and urban
      residence. Physical inactivity, morbid obesity (BMI>=30.0 kg/m2), higher number
      of chronic conditions, poor self-reported health, higher disability levels, and
      worse health status in terms of mobility, pain/discomfort, affect, sleep/energy
      and cognition were associated with high SB. Several between-country differences
      were found. CONCLUSION: The current data provides important guidance for future
      interventions across LMICs to assist sedentary people to reduce their SB levels.

PMID- 30096193
TI  - Comparison of two rapid diagnostic tests during a large dengue virus serotype 3
      outbreak in the Solomon Islands in 2013.
AB  - Dengue virus (DENV) infection causes various clinical presentations, including
      asymptomatic infection, dengue with or without warning signs and severe dengue.
      An early and accurate diagnosis of DENV infection during the first few days of
      illness supports clinical management and significantly reduces dengue-associated
      mortality and morbidity. However, it is very difficult to confirm DENV infection
      in endemic regions without qualified dengue diagnostic laboratories. In this
      study, we evaluated the performance of two commercially available rapid
      diagnostic tests (RDTs) using serum samples collected in the Solomon Islands
      during the 2013 DENV-3 outbreak. The sensitivity and specificity of the tests
      were calculated by comparing the results of DENV nonstructural protein 1 (NS1),
      IgM and IgG RDTs with those obtained by qRT-PCR. We also compared the results of
      the DENV IgM/IgG RDT with those obtained using an IgM/IgG capture enzyme-linked
      immune-sorbent assay (ELISA). The sensitivities of the SD and CTK NS1 RDTs were
      similar (90.9% and 92.6%), and the specificity of the SD NS1 RDT was
      significantly higher than that of the CTK NS1 RDT (100% versus 78.8%). The
      inclusion of IgM and IgG in the RDT did not significantly increase the
      sensitivity for DENV diagnosis. Compared with the SD IgM RDT, IgM capture ELISA
      had the same specificity but higher sensitivity. User-friendly RDTs remain the
      first choice and the most convenient tool in dengue endemic regions, where
      laboratory facilities and the corresponding infrastructure are lacking. Our study
      provided important and practical information for comparing the performance and
      validity of the different RDTs for rapid dengue detection.

PMID- 30096191
TI  - The crystal structure of KSHV ORF57 reveals dimeric active sites important for
      protein stability and function.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) is a gamma-herpesvirus closely
      associated with Kaposi's sarcoma, primary effusion lymphoma and multicentric
      Castleman disease. Open reading frame 57 (ORF57), a viral early protein of KSHV
      promotes splicing, stability and translation of viral mRNA and is essential for
      viral lytic replication. Previous studies demonstrated that dimerization of ORF57
      stabilizes the protein, which is critical for its function. However, the detailed
      structural basis of dimerization was not elucidated. In this study, we report the
      crystal structures of the C-terminal domain (CTD) of ORF57 (ORF57-CTD) in both
      dimer at 3.5 A and monomer at 3.0 A. Both structures reveal that ORF57-CTD binds
      a single zinc ion through the consensus zinc-binding motif at the bottom of each
      monomer. In addition, the N-terminal residues 167-222 of ORF57-CTD protrudes a
      long "arm" and holds the globular domains of the neighboring monomer, while the C
      terminal residues 445-454 are locked into the globular domain in cis and the
      globular domains interact in trans. In vitro crosslinking and nuclear
      translocation assays showed that either deletion of the "arm" region or
      substitution of key residues at the globular interface led to severe dimer
      dissociation. Introduction of point mutation into the zinc-binding motif also led
      to sharp degradation of KSHV ORF57 and other herpesvirus homologues. These data
      indicate that the "arm" region, the residues at the globular interface and the
      zinc-binding motif are all equally important in ORF57 protein dimerization and
      stability. Consistently, KSHV recombinant virus with the disrupted zinc-binding
      motif by point mutation exhibited a significant reduction in the RNA level of
      ORF57 downstream genes ORF59 and K8.1 and infectious virus production. Taken
      together, this study illustrates the first structure of KSHV ORF57-CTD and
      provides new insights into the understanding of ORF57 protein dimerization and
      stability, which would shed light on the potential design of novel therapeutics
      against KSHV infection and related diseases.

PMID- 30096194
TI  - Self-rated depression and eye diseases: The Beijing Eye Study.
AB  - PURPOSE: To assess the prevalence of depression in the general population of
      Beijing and its association with ocular diseases. METHODS: The population-based
      Beijing Eye Study was conducted in a rural and an urban region of Greater
      Beijing. The study participants underwent a detailed ophthalmological examination
      and an interview including questions on the socioeconomic background. Depressive
      symptoms were evaluated using a Chinese depression scale adapted from Zung's self
      rated depression scale. The total score of depression symptoms was 80. Depression
      was defined as having a depression score >44. RESULTS: Out of 3468 study
      participants, 3267 (94.2%) individuals (1419 men) with an age of 64.5+/-9.7 years
      (range: 50-93 years) participated in the interview and answered all questions on
      depression. The mean depression score was 25.0+/-5.9 (median: 23.3; range:20-64).
      Depression (depression score >44) was present in 66 individuals (2.0%; 95%
      confidence interval (CI): 1.5, 2.5), and 5 individuals (0.2%; 95%CI: 0.02,0.3)
      had a depression score >=59. In multivariate regression, analysis, a higher
      depression score was associated (regression coefficient r2: 0.22) with a higher
      number of days with dry eye feeling (P<0.001; standardized regression coefficient
      beta: 0.09; non-standardized regression coefficient B: 0.20; 95%CI: 0.12,0.29)
      and shorter corneal curvature radius (P = 0.03;beta:-0.04; B:1.01; 95%CI: -1.90,
      0.12), after adjusting for age, gender, region of habitation, body mass index,
      cognitive function score, life quality score and blood concentration of
      triglycerides. Adding age-related macular degeneration (P = 0.10), glaucoma (P =
      0.77), diabetic retinopathy (P = 0.77), nuclear cataract (P = 0.35), cortical
      cataract (P = 0.58) or posterior subcapsular cataract (P = 0.28) as single
      parameters to the model revealed no significant correlation with the depression
      score. Lower best corrected visual acuity showed a marginal significant
      association (P = 0.05; beta: 0.04; B: 1.56; 95%CI: -0.01, 3.13). CONCLUSIONS: Dry
      eye feeling was the only common ocular disorder associated with an increased
      depression score, while the occurrence of age-related macular degeneration, any
      type of glaucoma, diabetic retinopathy, any type of cataract and keratoconus were
      not significantly associated with an increased depression score. Lower visual
      acuity was marginally associated. The prevalence of depression in the population
      aged 50+ years in Greater Beijing was 2.0% (96%CI: 1.5, 2.5).

PMID- 30096195
TI  - Regulation of divergent cortisol responsiveness in European sea bass,
      Dicentrarchus labrax L.
AB  - Mechanisms regulating differences in cortisol responsiveness between low (LR) and
      high response (HR) individuals have been poorly studied. In this context, we
      aimed to study key regulatory processes in cortisol dynamics at the head kidneys
      of LR and HR European sea bass. To do so, resting plasma cortisol and ACTH
      concentrations were quantified in these fish. Additionally, the head kidneys of
      these individuals were superfused through an in vitro superfusion system and
      stimulated with the same amount of ACTH to assess their cortisol biosynthetic
      capacity. Moreover, the expression of important genes in cortisol regulation was
      assessed. Results showed that LR fish had lower resting cortisol concentrations
      than HR, although no differences existed in the circulating levels of ACTH.
      Additionally, the biosynthetic capacity of HR was higher than that of LR fish
      when in vitro stimulated with ACTH. At the molecular level, a statistically
      significant 3.4-fold higher expression of the ACTH receptor, mc2r, and a 2.3
      fold, though not significant, higher expression of 11beta-hydroxylase (cyp11b1),
      an enzyme involved in cortisol biosynthesis, was observed in the HR fish.
      Finally, a statistically significant 1.3-fold lower expression of 11beta
      hydroxysteroid dehydrogenase 2 (hsd11b2), an enzyme involved in cortisol
      inactivation, was observed in HR when compared to LR fish. Therefore, it was for
      the first time indicated that cortisol dynamics can also be regulated at the post
      production level in the head kidney. Collectively, our results highlight the
      crucial role of the interrenal tissue in the regulation of differences in
      cortisol response between LR and HR sea bass individuals.

PMID- 30096197
TI  - Correction: Perceived conflict of interest in health science partnerships.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0175643.].

PMID- 30096196
TI  - Functionally disconnected: A look at how study design influences neurofeedback
      data and mechanisms in attention-deficit/hyperactivity disorder.
AB  - Neurofeedback (NF) is a form of behavioral therapy used to treat e.g. attention
      deficit/hyperactivity disorder (ADHD). Briefly, subjects are fed-back a
      putatively dysfunctional parameter of their brain activity in real time and must
      learn to control it in a suggested direction. NF protocols for ADHD have been
      used in practice for decades, though no clear standards on NF design have been
      implemented. Furthermore, studies often present only data from the general
      outcome of the NF treatment and do not look at how exactly the NF paradigm
      affects brain functionality, or what exactly the NF is training. The current
      study is two-fold: firstly, we look at how the functional connectivity (FC)
      patterns within key networks associated with ADHD differ between rests, feedback
      trials, success and failure in a complete functional near-infrared spectroscopy
      based NF experiment on adults with ADHD. Secondly, due to methodological concerns
      discovered during the analysis of our data, we address important considerations
      in the design of NF that are often ignored in protocols being used widely in
      therapy and research today. In particular, we examine the common average
      reference and its impact on network activity as well as the importance of
      balancing the randomization in a design. Finally, we discuss how these
      methodological considerations may have influenced our FC results.

PMID- 30096199
TI  - Equity of antiretroviral treatment use in high HIV burden countries: Analyses of
      data from nationally-representative surveys in Kenya and South Africa.
AB  - OBJECTIVE: To assess changes and equity in antiretroviral therapy (ART) use in
      Kenya and South Africa. METHODS: We analysed national population-based household
      surveys conducted in Kenya and South Africa between 2007 and 2012 for factors
      associated with lack of ART use among people living with HIV (PLHIV) aged 15-64
      years. We considered ART use to be inequitable if significant differences in use
      were found between groups of PLHIV (e.g. by sex). FINDINGS: ART use among PLHIV
      increased from 29.3% (95% confidence interval [CI]: 22.8-35.8) to 42.5% (95%CI:
      37.4-47.7) from 2007 to 2012 in Kenya and 17.4% (95%CI: 14.2-20.9) to 30.3%
      (95%CI: 27.2-33.6) from 2008 to 2012 in South Africa. In 2012, factors
      independently associated with lack of ART use among adult Kenyan PLHIV were rural
      residency (adjusted odds ratio [aOR] 1.98, 95%CI: 1.23-3.18), younger age (15-24
      years: aOR 4.25, 95%CI: 1.7-10.63, and 25-34 years: aOR 5.16, 95%CI: 2.73-9.74
      versus 50-64 years), nondisclosure of HIV status to most recent sex partner (aOR
      2.41, 95%CI: 1.27-4.57) and recent recreational drug use (aOR 2.50, 95%CI: 1.09
      5.77). Among South African PLHIV in 2012, lack of ART use was significantly
      associated with younger age (15-24 years: aOR 4.23, 95%CI: 2.56-6.70, and 25-34
      years: aOR 2.84, 95%CI: 1.73-4.67, versus 50-64 years), employment status (aOR
      1.61, 95%CI: 1.16-2.23 in students versus unemployed), and recent recreational
      drug use (aOR 4.56, 95%CI: 1.79-11.57). CONCLUSION: Although we found substantial
      increases in ART use in both countries over time, we identified areas needing
      improvement including among rural Kenyans, students in South Africa, and among
      young people and drug users in both countries.

PMID- 30096198
TI  - Relative survival in patients with dementia with Lewy bodies and Parkinson's
      disease dementia.
AB  - INTRODUCTION: The understanding of survival in dementia with Lewy bodies (DLB)
      and Parkinson's disease dementia (PDD) is limited, as well as the impact of these
      diagnoses in an ageing co-morbid population. METHODS: A retrospective study of
      177 patients who received a DLB or PDD diagnosis between 1997-2014 at the Memory
      Clinic in Malmo, Sweden. Relative survival was evaluated by adjusting all-cause
      survival for expected survival, estimated from population life-tables, matched by
      sex, age and calendar year. Predictors of relative survival were investigated
      using multivariate regression modelling. RESULTS: At follow-up, 143 (81%)
      patients were deceased with a median survival of 4.1 years (IQR 2.6-6.0). After
      10-years follow-up, the standardized mortality ratio was 3.44 (95% CI 2.92-4.04).
      Relative survival was worse with younger age at diagnosis (excess hazard ratio
      [eHR] 0.91, 95% CI 0.88-0.94 per year of age), female sex (eHR 1.45, 95% CI 1.01
      2.09) and lower mini-mental state examination (eHR 0.93, 95% CI 0.90-0.96).
      Subgroup analysis (n = 141) showed higher mortality in DLB patients who were
      positive for APOE E4 (eHR 2.00, 95% CI 1.35-2.97). CONCLUSION: The mortality is
      over three-times higher in patients diagnosed with dementia with Lewy bodies and
      Parkinson's disease dementia during a ten-year follow-up, compared to persons in
      the general population. Excess mortality is found primarily in younger patients,
      females and carriers of APOE epsilon4. Further research is needed regarding
      survival and possible interventions, including disease-modifying treatments, to
      improve care for this patient group.

PMID- 30096200
TI  - Amino-acid-enriched cereals ready-to-use therapeutic foods (RUTF) are as
      effective as milk-based RUTF in recovering essential amino acid during the
      treatment of severe acute malnutrition in children: An individually randomized
      control trial in Malawi.
AB  - BACKGROUND: Ready-to-use therapeutic food (RUTF) is used to treat children
      suffering from severe acute malnutrition (SAM). Standard RUTF uses milk as the
      primary protein source, which makes the product expensive, and given the high
      worldwide SAM burden, having a less expensive effective alternative is a public
      health priority. OBJECTIVE: The objective of this study was to evaluate whether
      newly developed amino acid-enriched milk-free RUTF (FSMS-RUTF) or amino acid
      enriched low-milk RUTF (MSMS-RUTF) treatment could replenish plasma amino acids
      to levels comparable to those following standard peanut-milk RUTF (PM-RUTF)
      treatment and to improve understanding of the effects of treatment on
      anthropometric measurements. A secondary analysis was performed to test the
      noninferiority hypothesis of plasma essential amino acid (EAA) levels. METHODS:
      Plasma EAA levels were measured in a nonblinded, 3-arm, parallel-group simple
      randomized controlled trial conducted in Malawi to examine the efficacy of FSMS
      RUTF, MSMS-RUTF and PM-RUTF in the treatment of SAM in 2 groups of children aged
      6-23 and 24-59 months (mo). Sample size calculations were performed based on the
      previous our study. A noninferiority margin was set at -25% of the PM-RUTF arm at
      discharge. RESULTS: The relative values of the differences (95% CI) in plasma EAA
      levels between PM-RUTF treatment and FSMS-RUTF and MSMS-RUTF treatments at
      discharge were -7.9% (-18.6, 2.8) and 9.8% (0.2, 19.5), respectively, in children
      aged 6-23 mo, while in those aged 24-59 mo, the difference values were 17.8%
      (1.6, 34.1) and 13.6% (-2.8, 29.9), respectively. CONCLUSION: At discharge, the
      plasma EAA concentrations in 6-59-mo-old SAM children treated with FSMS-RUTF and
      MSMS-RUTF were not less than those of children treated with PM-RUTF. These
      findings indicate that treatment with either of the 3 RUTFs was associated with
      adequate protein synthesis and that all the formulations provided sufficient
      functional metabolites of plasma amino acids to support nutritional recovery from
      SAM.

PMID- 30096201
TI  - Transition to universal primary health care coverage in Brazil: Analysis of
      uptake and expansion patterns of Brazil's Family Health Strategy (1998-2012).
AB  - Family Health Strategy, the primary health care program in Brazil, has been
      scaled up throughout the country, but its expansion has been heterogeneous across
      municipalities. We investigate if there are unique municipal characteristics that
      can explain the timing of uptake and the pattern of expansion of the Family
      Health Strategy from years 1998 to 2012. We categorized municipalities in six
      groups based on the relative speed of the Family Health Strategy uptake and the
      pattern of Family Health Strategy coverage expansion. We assembled data for 11
      indicators for years 2000 and 2010, for 5,507 municipalities, and assessed
      differences in indicators across the six groups, which we mapped to examine
      spatial heterogeneities. Important factors differentiating early and late
      adopters of the Family Health Strategy were supply of doctors and population
      density. Sustained coverage expansion was related mainly to population size,
      marginal benefits of the program and doctors' supply. The uptake was widespread
      nationwide with no distinct patterns among regions, but highly heterogeneous at
      the state and municipal level. The Brazilian experience of expanding primary
      health care offers three lessons in relation to factors influencing diffusion of
      primary health care. First, the funding mechanism is critical for program
      implementation, and must be accompanied by ways to support the supply of primary
      care physicians in low density areas. Second, in more developed and bigger areas
      the main challenge is lack of incentives to pursue universal coverage, especially
      due to the availability of private insurance. Third, population size is a crucial
      element to guarantee coverage sustainability over time.

PMID- 30096202
TI  - Quantitative screening of the pharmaceutical ingredient for the rapid
      identification of substandard and falsified medicines using reflectance infrared
      spectroscopy.
AB  - The World Health Organization suggests that approximately 10% of medicines
      worldwide are either falsified or substandard with higher figures in low and
      middle income countries. Such poor quality medicines can seriously harm patients
      and pose a threat to the economy worldwide. This study investigates attenuated
      total reflectance-fourier transform infrared (ATR-FTIR) spectroscopy as a simple
      and rapid method for determination of drug content in tablet dosage forms.
      Paracetamol was used as the model pharmaceutical ingredient. Spectra of standard
      mixtures of paracetamol with different excipients formed the basis for
      multivariate PLS based quantitative analysis of simulated tablet content using
      different selected infrared absorbance bands. Calibration methods using ATR-FTIR
      were compared with the ATR-FTIR and conventional ultraviolet spectroscopic
      analyses of real tablet samples and showed that the paracetamol/microcrystalline
      cellulose mixtures gave optimum results for all spectral bands tested. The
      quantitative data for band 1524-1493cm-1 was linear (R2 ? 0.98; LOQ >= 10%w/w
      tablet). Global examples of paracetamol tablets were tested using this protocol
      and 12% of the tablet samples examined was identified as substandard. Each sample
      analysis was completed in just a few minutes. ATR-FTIR can therefore be used in
      the rapid screening of tablet formulations. The simplicity of the proposed method
      makes it appropriate for use in low and middle income countries where analytical
      facilities are not available.

PMID- 30096204
TI  - Correction: Impact of clinical severity of stroke on the severity and recovery of
      visuospatial neglect.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198755.].

PMID- 30096203
TI  - Cognitive and behavioural strategies for weight management in overweight adults:
      Results from the Oxford Food and Activity Behaviours (OxFAB) cohort study.
AB  - BACKGROUND: Though many overweight and obese adults attempt to lose weight
      without formal support, little is known about the strategies used in self
      directed weight loss attempts. We set out to assess cognitive and behavioural
      strategies for weight loss and their associations with weight change. METHODS:
      Prospective, web-based cohort study of overweight UK adults (BMI>=25kg/m2) trying
      to lose weight through behaviour change. Strategy use was assessed using the
      OxFAB questionnaire and evaluated (1) at the domain level, (2) through
      exploratory factor analysis, and (3) in a model of strategies deemed a priori to
      be "essential" to weight management. Associations with weight change at 3 months
      were tested using linear regression. RESULTS: 486 participants answered all
      questions; 194 reported weight at baseline and at 3 months (mean weight change 
      3.3kg (SD 4.1)). Greater weight loss was significantly associated with the
      motivational support domain (-2.4kg, 95% CI -4.4 to -0.4), dietary impulse
      control (from factor analysis) (-0.6kg, 95% CI -1.1 to -0.03), and weight loss
      planning and monitoring (from factor analysis) (-1.3kg, 95% CI -2.0 to -0.5).
      Higher scores in the model of essential behavioural strategies were significantly
      associated with greater weight loss (compared to participants using 6 or fewer of
      the 9 strategies, using 7 or more of the 9 strategies was associated with a
      2.13kg greater weight loss (SE 0.58, p<0.001)). CONCLUSIONS: Despite
      heterogeneity in the strategies employed for weight loss, coherent patterns of
      behaviours emerged for individual participants, some of which were associated
      with greater weight loss, including strategies relating to dietary impulse
      control, weight loss planning and monitoring, motivational support, information
      seeking and self-monitoring. Trials could test the effect of promoting use of
      these patterns on weight loss.

PMID- 30096205
TI  - Evaluation of six decontamination procedures for isolation of Mycobacterium avium
      complex from avian feces.
AB  - Culture is considered the gold standard for definitive diagnosis of mycobacterial
      infections. However, consensus about the most suitable culture procedure for
      isolation of nontuberculous mycobacteria is lacking. The study compared the
      recoveries of mycobacteria after decontamination of spiked and fresh avian feces
      with 4% sodium hydroxide (NaOH), 12% sulfuric acid (H2SO4), or 1% cetylperidinium
      chloride (CPC), with and without mixture of three antibiotics, namely vancomycin
      (VAN, 100 MUg/ml), nalidixic acid (NAL, 100 MUg/ml), and amphotericin B (AMB, 100
      MUg/ml). The antibiotic mixture was referred to as VNA. Decontamination
      procedures were evaluated using two (n = 2) avian fecal samples spiked with 106,
      104, and 102 CFU/ml of Mycobacterium avium subsp. avium (ATCC 15769) and fresh
      avian feces (n = 42). M. avium subsp. avium was detected on the culture media
      from spiked samples (106 and 104 CFU/ml) decontaminated with NaOH, NaOH-VNA,
      H2SO4, and H2SO4 -VNA for 2-6 weeks. These bacteria were detected in 2-4 weeks
      when using CPC and CPC-VNA. M. avium subsp. avium cannot be isolated on culture
      media from spiked samples (102 CFU/ml) decontaminated with any decontaminating
      agent. Two mycobacterial isolates, namely, Mycobacterium terrae and M. engbaekii,
      were isolated from field samples decontaminated with NaOH and CPC-VNA. With
      regard to the contamination rate, the use of CPC-VNA showed lower contamination
      rates (5.5% and 19.0%) from spiked and field samples than those of the other
      methods (NaOH: 22.2% and 59.5%, NaOH-VNA: 16.7% and 21.4%, H2SO4: 11.1% and
      40.5%, H2SO4-VNA: 5.5% and 21.4%, and CPC: 66.7% and 50%). In conclusion, the
      decontamination of fecal samples following a two-step procedure with 1% CPC and
      VNA can ensure high recovery rate of many mycobacteria with the lowest
      contamination in cultures.

PMID- 30096207
TI  - Improvement of safflower oil quality for biodiesel production by integrated
      application of PGPR under reduced amount of NP fertilizers.
AB  - Safflower is an important industrial oil seed and bioenergy crop in semi-arid
      subtropical regions due to its potential to grow on marginal land and having good
      percentage of seed oil contents which is an important parameter for biofuel
      production. However, it is an ignored crop in Pakistan. In order to improve the
      crop productivity and reduce the use of agrochemicals for sustainable biodiesel
      feedstock production, an experiment was conducted for two years to improve the
      fatty acid composition and oil quality of Carthamus tinctorius L. (safflower) by
      the inoculation of Azospirillum and Azotobacter alone as well as in combined
      application with nitrogen and phosphate (NP) fertilizers on cultivars Thori and
      Saif-32 under field conditions. Separation and quantification of fatty acids were
      done on precise comprehensive two-dimensional gas chromatography (GC*GC). The
      results showed that fatty acid profile specifically monounsaturated fatty acids i
      e oleic acid (C18:1) was significantly improved by Azospirillum supplemented with
      the quarter dose of NP fertilizers (SPQ) with concomitant decrease in
      polyunsaturated fatty acids by the respective treatment. Oil quality attributes
      such as acid value, saponification number, iodine value, refractive index and
      free fatty acid contents were reduced by the application of Azotobacter and
      Azospirillum in combination with half and quarter doses of NP fertilizers
      treatments (BTH, SPH, BTQ and SPQ). The reduction in these variables is
      positively linked with improved biodiesel yield and quality. It can be concluded
      that application of Azospirillum and Azotobacter not only reduced the use of NP
      fertilizers up to 50%-75% but also improved the oil quality in order to obtain
      environment friendly, sustainable and green fuel.

PMID- 30096206
TI  - Attitudes toward evidence-based practices, occupational stress and work-related
      social support among health care providers in China: A SEM analysis.
AB  - Individuals' attitudes toward evidence-based practices (EBP) are critical in
      adopting, implementing and maintaining the EBP in clinical settings. Multiple
      empirical studies have examined how work context may shape perceptions and
      attitudes towards EBP. The current study aims to further explore how both work
      and family contexts, as assessed by three psychosocial indicators (i.e.,
      occupational stress, work-related social support from coworkers, and work-related
      social support from family), may affect attitudes toward EBP among health care
      providers in HIV clinics in China. We analyzed cross-sectional survey data from
      357 health care providers recruited from 40 HIV clinics across 16 cities/counties
      in Guangxi China. Structural equation model (SEM) was constructed to test the
      hypothesized relationships among key study variables. Occupational stress was
      negatively associated with work-related social support from coworkers (beta = 
      .19, 95%CI = [-.31,-.12]), which in turn was positively associated with attitudes
      toward EBP (beta = .17, 95%CI = [.04, .30]). Similarly, occupational stress was
      negatively related to work-related social support from family (beta = -.34, 95%CI
      = [-.42,-.25]), which in turn was positively related to attitudes toward EBP
      (beta = .23, 95%CI = [.12, .35]). Occupational stress was negatively associated
      with attitudes toward EBP, but the magnitude of association did not reach
      statistical significance at alpha = .05. Work-related social support from family
      partially mediated the association between occupational stress and attitudes
      toward EBP (Sobel's z = 3.27, p < .05). Our findings suggest the importance of
      integrating work and family contexts, especially family support into the
      strategies of facilitating the adoption and implementation of EBP. The current
      study also underscores the needs to reduce occupational stress and enhance work
      related social support among health care providers who are in frequent contact
      with HIV patients. In addition, lack of work-related family support may be a main
      barrier preventing health care providers from developing a positive attitude
      toward EBP. Therefore, the interventions aiming for promoting adoption and
      utilization of EBP need to involve specific strategies to resolve work-family
      conflicts and improve family members' understanding and support for health care
      providers in China, especially those who work in a stressful work context such as
      HIV care.

PMID- 30096208
TI  - Macrophage CD40 plays a minor role in obesity-induced metabolic dysfunction.
AB  - Obesity is a low-grade inflammatory disease that increases the risk for metabolic
      disorders. CD40-CD40L signaling plays a central role in obesity-induced
      inflammation. Genetic deficiency of CD40L in diet-induced obesity (DIO)
      ameliorates adipose tissue inflammation, hepatic steatosis and increases insulin
      sensitivity. Unexpectedly, absence of CD40 worsened insulin resistance and caused
      excessive adipose tissue inflammation and hepatosteatosis. To investigate whether
      deficiency of macrophage CD40 is responsible for the phenotype observed in the
      CD40-/- mice, we generated CD40flflLysMcre and fed them a standard (SFD) and 54%
      high fat obesogenic diet (HFD) for 13 weeks. No differences in body weight,
      adipose tissue weight, adipocyte size, plasma cholesterol or triglyceride levels
      could be observed between CD40flflLysMcre and wild type (WT) mice.
      CD40flflLysMcre displayed no changes in glucose tolerance or insulin resistance,
      but had higher plasma adiponectin levels when fed a SFD. Liver weights, liver
      cholesterol and triglyceride levels, as well as the degree of hepatosteatosis
      were not affected by absence of macrophage CD40. CD40flflLysMcre mice displayed a
      minor increase in adipose tissue leukocyte infiltration on SFD and HFD, which did
      not result in differences in adipose tissue cytokine levels. We here show that
      loss of macrophage CD40 signaling does not affect obesity induced metabolic
      dysregulation and indicates that CD40-deficiency on other cell-types than the
      macrophage is responsible for the metabolic dysregulation, adipose tissue
      inflammation and hepatosteatosis that are observed in CD40-/- mice.

PMID- 30096209
TI  - Antimicrobial efficacy and compatibility of solid copper alloys with chemical
      disinfectants.
AB  - INTRODUCTION: Chemical disinfection is state of the art in preventing spread of
      infectious agents in the healthcare setting. Additionally, the antimicrobial
      properties of solid copper alloy surfaces against various microorganisms have
      recently been substantiated. Thus, antimicrobially active copper surfaces may
      serve as an additional barrier against distribution of pathogenic microorganisms
      and be combined with chemical disinfection measures in the hospital. The aim of
      this study was therefore to investigate on a quantitative basis whether the
      combination of chemical disinfectants with copper alloy surfaces results in an
      overall compromised, combined or even synergistic antimicrobial efficacy.
      METHODS: Experiments were carried out using the quantitative carrier test devised
      by the German Society for Hygiene and Microbiology (DGHM) to study antimicrobial
      efficacy of chemical disinfectants. Requirements for microbicidal efficacy as
      defined by prEN 14885 were applied. The chemical disinfectants tested in our
      study contained alcohols (ethanol, 1-propanol), quaternary ammonium compounds
      (benzalkonium chloride) and glutaraldehyde as actives. Quantitative carrier tests
      were carried out on different carriers (tiles, copper alloy discs, stainless
      steel discs) using Pseudomonas aeruginosa, Staphylococcus aureus, Kocuria
      rhizophila and Candida albicans as test organisms. RESULTS: For the alcohol-based
      disinfectant no difference in antimicrobial efficacy was observed when applied to
      antimicrobial active copper alloy carriers, tiles or stainless steel discs. For
      all test organisms microbial contamination was reduced to the detection limit of
      < 1 log (CFU/ml) within a contact time of 2 min indicating a >= 5 log reduction
      for the tested bacteria and a >= 4 log reduction for the yeast, as being
      requested for chemical disinfectants by prEN 14885. In order to elucidate a
      potential synergism the chemical disinfectant based on quaternary ammonium
      compounds (benzalkonium chloride) and glutaraldehyde was used at a sub-effective
      concentration. Hence, no complete reduction of microbial contamination was
      achieved on stainless steel or tile carriers for Pseudomonas aeruginosa and
      Candida albicans. Interestingly, when using copper alloy carriers complete
      reduction indicating a >= 5 log reduction for P. aeruginosa and a >= 4 log
      reduction for C. albicans was detected. Thus, data of this study indicates that
      solid copper alloy surfaces and disinfectants synergize. CONCLUSIONS: According
      to this data, commercially available disinfectants based on alcohol, quaternary
      ammonium compounds and aldehyde can effectively be combined in a dual strategy
      with solid copper alloy surfaces to reduce microbial contamination.

PMID- 30096210
TI  - Effects of flower thrips (Thysanoptera: Thripidae) on nutritional quality of
      banana (Zingiberales: Musaceae) buds.
AB  - The abundance of banana flower thrips (Thrips hawaiiensis Morgan) in a banana
      (Musa acuminata Colla "Williams" cultivar) plantation was investigated using
      yellow sticky traps (29.70 cm * 21.00 cm) in 2015. Banana flower thrips occurred
      throughout the year with monthly variation, and the maximum occurrence was
      observed in October and November during the bud burst (73.80 +/- 6.32
      adults/trap) and young fruit (70.06 +/- 5.69 adults/trap) periods. The damage
      rates were as follows: interior flowers >3rd-layer flowers > 2nd-layer flowers >
      1st-layer flowers > young fruits. This result indicates that thrips migrated to
      lower bracts, young fruits, and other flower buds as bracts gradually opened.
      Results also showed that the reducing sugar, vitamin C, protein and ash contents
      in thrips-damaged flowers were all significantly lower than those in undamaged
      flowers, while there was no significant difference between damaged and undamaged
      young banana fruit. Our results indicated that the abundances of banana flower
      thrips were closely associated with the growing stage of banana. Thrips mainly
      infested flower buds and caused a reduction in nutrients for the host plant,
      especially the reducing sugar and vitamin C contents, which reduced the
      nutritional quality of banana fruits and the quality of flower bud by-products of
      banana.

PMID- 30096211
TI  - Online dietary intake assessment using a graphical food frequency app (eNutri):
      Usability metrics from the EatWellUK study.
AB  - BACKGROUND: With widespread use of the internet, lifestyle and dietary data
      collection can now be facilitated using online questionnaires as opposed to paper
      versions. We have developed a graphical food frequency assessment app (eNutri),
      which is able to assess dietary intake using a validated food frequency
      questionnaire (FFQ) and provide personalised nutrition advice. FFQ user
      acceptance and evaluation have not been investigated extensively and only a few
      studies involving user acceptance of nutrition assessment and advice apps by
      older adults are published. METHODS: A formative study with 20 participants
      (including n = 10 >=60 years) assessed the suitability of this app for adults and
      investigated improvements to its usability. The outcomes of this formative study
      were applied to the final version of the application, which was deployed in an
      online study (EatWellUK) with 324 participants (including n = 53 >=60 years) in
      the UK, using different devices (smartphones, tablets and laptops/desktops).
      Completion times were based on browser timestamps and usability was measured
      using the System Usability Scale (SUS), scoring between 0 and 100. Products with
      a SUS score higher than 70 are considered to be good. RESULTS: In the EatWellUK
      study, SUS score median (n = 322) was 77.5 (IQR 15.0). Out of the 322 SUS
      questionnaire completions, 321 device screen sizes were detected by the app.
      Grouped by device screen size, small (n = 92), medium (n = 38) and large (n =
      191) screens received median SUS scores of 77.5 (IQR 15.0), 75.0 (IQR 19.4) and
      77.5 (IQR 16.25), respectively. The median SUS scores from younger (n = 268) and
      older participants (n = 53) were the same. The FFQ contained 157 food items, and
      the mean completion time was 13.1 minutes (95% CI 12.6-13.7 minutes). Small,
      medium and large screen devices resulted in completion times of 11.7 minutes (95%
      CI 10.9-12.6 minutes), 14.4 minutes (95% CI 12.9-15.9 minutes) and 13.6 minutes
      (95% CI 12.8-14.3 minutes), respectively. CONCLUSIONS: The overall median SUS
      score of 77.5 and overall mean completion time of 13.3 minutes indicate good
      overall usability, and equally, comparable SUS scores and completion times across
      small, medium and large screen sizes indicates good usability across devices.
      This work is a step toward the promotion of wider uptake of online apps that can
      provide online dietary intake assessment at-scale, with the aim of addressing
      pressing epidemiological challenges.

PMID- 30096212
TI  - Gray matter bases of psychotic features in adult bipolar disorder: A systematic
      review and voxel-based meta-analysis of neuroimaging studies.
AB  - Psychotic bipolar disorder (P-BD) is a specific subset that presents greater risk
      of relapse and worse outcomes than nonpsychotic bipolar disorder (NP-BD). To
      explore the neuroanatomical bases of psychotic dimension in bipolar disorder
      (BD), a systematic review was carried out based on the gray matter volume (GMV)
      among P-BD and NP-BD patients and healthy controls (HC). Further, we conducted a
      meta-analysis of GMV differences between P-BD patients and HC using a whole-brain
      imaging approach. Our review revealed that P-BD patients exhibited smaller GMVs
      mainly in the prefronto-temporal and cingulate cortices, the precentral gyrus,
      and insula relative to HC both qualitatively and quantitatively. Qualitatively
      the comparison between P-BD and NP-BD patients suggested inconsistent GMV
      alterations mainly involving the prefrontal cortex, while NP-BD patients showed
      GMV deficits in local regions compared with HC. The higher proportions of female
      patients and patients taking psychotropic medication in P-BD and P-BD type I were
      associated with smaller GMV in the right precentral gyrus, and the right insula,
      respectively. In conclusions, psychosis in BD might be associated with specific
      cortical GMV deficits. Gender and psychotropic medication might have effects on
      the regional GMVs in P-BD patients. It is necessary to distinguish psychotic
      dimension in neuroimaging studies of BD.

PMID- 30096213
TI  - Brainstem network disruption: A pathway to sudden unexplained death in epilepsy?
AB  - Observations in witnessed Sudden Unexpected Death in Epilepsy (SUDEP) suggest
      that a fatal breakdown of the central autonomic control could play a major role
      in SUDEP. A previous MR study found volume losses in the mesencephalon in focal
      epilepsy that were more severe and extended into the lower brainstem in two
      patients who later died of SUDEP. The aims of this study were to demonstrate an
      association (1) between brainstem volume loss and impaired autonomic control
      (reduced heart rate variability [HRV]); (2) between brainstem damage and time to
      SUDEP in patients who later died of SUDEP. Two populations were studied: (1)
      Autonomic system function population (ASF, 18 patients with focal epilepsy, 11
      controls) with HRV measurements and standardized 3 T MR exams. (2) SUDEP
      population (26 SUDEP epilepsy patients) with clinical MRI 1-10 years before
      SUDEP. Deformation-based morphometry of the brainstem was used to generate
      profile similarity maps from the resulting Jacobian determinant maps that were
      further characterized by graph analysis to identify regions with excessive
      expansion indicating significant volume loss or atrophy. The total number of
      regions with excessive expansion in ASF was negatively correlated with HRV (r = 
      .37, p = .03), excessive volume loss in periaqueductal gray/medulla oblongata
      autonomic nuclei explained most of the HRV associated variation (r/r2  = 
      .82/.67, p < .001). The total number of regions with excessive expansion in SUDEP
      was negatively correlated with time to SUDEP (r = -.39, p = .03), excessive
      volume loss in the raphe/medulla oblongata at the obex level explained most of
      the variation of the time between MRI to SUDEP (r/r2  = -.60/.35,p = .001).
      Epilepsy is associated with brainstem atrophy that impairs autonomic control and
      can increase the risk for SUDEP if it expands into the mesencephalon.

PMID- 30096214
TI  - Feelings About Fracking: Using the Affect Heuristic to Understand Opposition to
      Coal Seam Gas Production.
AB  - The rapid expansion of coal seam gas (CSG) extraction across Australia has
      polarized public opinion about the risks, benefits, and the future of the
      industry. We conducted a randomized controlled experiment to assess the impact of
      CSG messaging on opposition to the CSG industry. Residents of a major Australian
      city (N = 549), aged between 21 and 87 years, were randomly assigned to view one
      of three brief video messages (pro-CSG, anti-CSG, or a neutral control) sourced
      from the Internet. They then completed measures assessing CSG affective
      associations, perceived risks and benefits of CSG, and degree of opposition to
      the CSG industry. A subsample of 317 participants also completed the measures of
      affect, risks, benefits, and opposition two weeks following the initial message
      presentation. Message type significantly predicted message effects in a pattern
      consistent with the affect heuristic model, although overall, the message effects
      were modest in magnitude. Respondents who viewed the anti-CSG video (relative to
      the control) reported more negative affective responses to CSG, perceived higher
      risks, fewer benefits, and greater opposition to the CSG industry. Those who
      viewed the pro-CSG video (relative to the control) reported stronger positive
      affective responses to CSG, perceived more CSG benefits and fewer risks, and
      expressed less opposition to the industry. The effects persisted over a two-week
      interval for the anti-CSG message, but not for the pro-CSG message. Our findings
      suggest that people's risk perceptions and views about the acceptability of CSG
      are malleable by messaging that targets affective pathways.

PMID- 30096215
TI  - Mechanical dilatation of the cervix during elective caeserean section before the
      onset of labour for reducing postoperative morbidity.
AB  - BACKGROUND: During elective (planned) caesarean sections, some obstetricians
      routinely dilate the cervix intraoperatively, using sponge forceps, a finger, or
      other instruments, because the cervix of women not in labour may not be dilated,
      and this may cause obstruction of blood or lochia drainage. However, mechanical
      cervical dilatation during caesarean section may result in contamination by
      vaginal micro-organisms during dilatation, and increase the risk of infection or
      cervical trauma. OBJECTIVES: To determine the effects of mechanical dilatation of
      the cervix during elective caesarean section on postoperative morbidity. SEARCH
      METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry
      Platform (ICTRP) and reference lists of retrieved studies on 20 September 2017.
      SELECTION CRITERIA: We included all randomised, quasi-randomised, and cluster
      randomised controlled trials comparing intraoperative cervical dilatation using a
      finger, sponge forceps, or other instruments during elective caesarean section
      versus no mechanical dilatation. DATA COLLECTION AND ANALYSIS: Two review authors
      independently assessed trials for inclusion and risk of bias, extracted data and
      checked them for accuracy. We assessed the quality of the evidence using the
      GRADE approach. MAIN RESULTS: We included eight studies with a total of 2227
      women undergoing elective caesarean section. Of these, 1097 underwent
      intraoperative cervical dilatation with a double-gloved index finger or Hegar
      dilator inserted into the cervical canal to dilate, and 1130 did not undergo
      intraoperative cervical dilatation. Six of the eight included trials had high
      risk of bias for some of the risk of bias domains.Very low-quality evidence
      suggested it was unclear whether cervical dilatation had any impact on postpartum
      haemorrhage (estimated blood loss greater than 1000 mL; risk ratio (RR) 1.97, 95%
      confidence interval (CI) 0.48 to 8.13; 5/205 versus 3/242; one study, 447
      women).Low- or very low-quality evidence showed no clear difference for the need
      for blood transfusion (RR 3.54, 95% CI 0.37 to 33.79; two studies, 847 women);
      postoperative haemoglobin (mean difference (MD -0.05, 95% CI -0.15 to 0.06; three
      studies, 749 women), or haematocrit (MD 0.01%, 95% CI -0.18 to 0.20; one study,
      400 women); the incidence of drop from baseline haemoglobin above 0.5 g/dL (RR
      0.92, 95% CI 0.64 to 1.31; two studies, 722 women), or amount of haemoglobin drop
      (MD -0.01 g/dL, 95% -0.14 to 0.13; three studies, 796 women); the incidence of
      secondary postpartum haemorrhage within six weeks (RR 1.18, 95% CI 0.07 to 18.76;
      one study, 447 women); febrile morbidity (RR 1.18, 95% CI 0.76 to 1.85; seven
      studies, 2126 women); endometritis (RR 0.94, 95% CI 0.35 to 2.52; four studies,
      1536 women); or uterine subinvolution (RR 0.34, 95% CI 0.08 to 1.36; two studies,
      654 women); the results crossed the line of no effect for all of the outcomes.
      There were no data for cervical trauma.We found a slight improvement with
      mechanical dilatation for these secondary outcomes, not prespecified in the
      protocol: mean blood loss, endometrial cavity thickness, retained products of
      conception, distortion of uterine incision, and healing ratio. The evidence for
      these outcomes was based on one or two studies. Cervical dilatation did not have
      a clear effect on these secondary outcomes, not prespecified in the protocol:
      wound infection, urinary tract infection, operative time, infectious morbidity,
      and integrity of uterine scar. AUTHORS' CONCLUSIONS: At this time, the evidence
      does not support or refute the use of mechanical dilatation of the cervix during
      elective caesarean section for reducing postoperative morbidity.Further large,
      well-designed studies are required to compare the effect of intraoperative
      mechanical dilatation of the cervix with no intraoperative mechanical cervical
      dilatation for reducing postoperative morbidity.

PMID- 30096216
TI  - Reduced local segregation of single-subject gray matter networks in adult PTSD.
AB  - To psychoradiologically investigate the topological organization of single
      subject gray matter networks in patients with PTSD. Eighty-nine adult PTSD
      patients and 88 trauma-exposed controls (TEC) underwent a structural T1 magnetic
      resonance imaging scan. The single-subject brain structural networks were
      constructed based on gray matter similarity of 90 brain regions. The area under
      the curve (AUC) of each network metric was calculated and both global and nodal
      network properties were measured in graph theory analysis. We used nonparametric
      permutation tests to identify group differences in topological metrics.
      Relationships between brain network measures and clinical symptom severity were
      analyzed in the PTSD group. Compared with TEC, brain networks of PTSD patients
      were characterized by decreased clustering coefficient (Cp ) (p = .04) and local
      efficiency (Eloc ) (p = .04). Locally, patients with PTSD exhibited altered nodal
      centrality involving medial superior frontal (mSFG), inferior orbital frontal
      (iOFG), superior parietal (SPG), middle frontal (MFG), angular, and para
      hippocampal gyri (p < .05, corrected). A negative correlation between the
      segregation (Cp ) of gray matter and functional networks was found in PTSD
      patients but not the TEC group. Analyses of topological brain gray matter
      networks indicate a more randomly organized brain network in PTSD. The reduced
      segregation in gray matter networks and its negative relation with increased
      segregation in the functional network indicate an inverse relation between gray
      matter and functional changes. The present psychoradiological findings may
      reflect a compensatory increase in functional network segregation following a
      loss of segregation in gray matter networks.

PMID- 30096217
TI  - Chronic exposure to environmental stressors enhances production of natural and
      specific antibodies in rats.
AB  - Although the immunosuppressive effect of chronic stress has been established, a
      stress response that downregulates the whole immune system does not make
      biological sense, especially if an animal has to endure difficult times in which
      there is also increased infection risk. At high animal densities, animals are
      faced simultaneously with food restriction (FR), social conflict (SC), and
      greater parasite-pathogen exposure. We hypothesized that the stress response to
      chronic stressors that covary with infection risk is not entirely
      immunosuppressive. Our prediction was that a chronically stressed animal would
      respond by enhancing innate defenses, while reducing investment in acquired
      immunity. In a laboratory setting, rats were exposed to prolonged FR and/or SC,
      and natural and specific antibody levels were repeatedly measured. Our prediction
      was fulfilled only partly, as FR and SC interacted to enhance natural antibodies,
      but rats exposed to either or both stressors also showed significantly higher
      levels of specific antibodies. These results suggest that, in the rat, chronic
      stress results in a prioritization of both innate and acquired humoral defenses,
      which makes biological sense provided the stressors examined usually signal an
      increased infection risk.

PMID- 30096218
TI  - Three-dimensional printing of poly(glycerol sebacate fumarate) gadodiamide
      poly(ethylene glycol) diacrylate structures and characterization of mechanical
      properties for soft tissue applications.
AB  - Bioresorbable materials have been frequently used to three-dimensional (3D) print
      biomedical structures. In this study, we developed a technique to 3D print
      poly(glycerol sebacate fumarate) gadodiamide (Rylar)-poly(ethylene glycol)
      diacrylate (PEGDA) samples and investigated their mechanical and thermal
      properties as a function of (PS) and ultraviolet intensity (UVI). The Young's
      modulus (E), ultimate tensile strength (UTS), failure strain (EF ), and glass
      transition temperature (Tg ) showed strong correlation with PS and UVI. Results
      showed E to be between 1.31 and 3.12 MPa, UTS between 0.07 and 0.43 MPa, and EF
      between 7 and 20% with brittle failure. The Tg was observed to lie between -54.48
      and -49.10 degrees C without secondary/tertiary transitions. Dominant elastic
      behavior was observed from the dynamic mechanical testing viscoelastic data.
      Testing results were used to develop a regression predictive model for E as a
      function of PS and UVI. The model performance was evaluated experimentally with
      an average absolute error of 3.62%. The E and stress-strain response of our 3D
      printed samples show agreement with published data for human tracheal cartilage,
      and the mechanical properties were comparable to other published soft polymeric
      scaffolds/patches. The E' moduli were also similar to bovine articular cartilage.
      We have successfully demonstrated that Rylar, a novel bioresorbable radiopaque
      polymer, when blended with PEGDA can be 3D printed controllably for soft tissue
      applications such as airway obstructions. (c) 2018 Wiley Periodicals, Inc. J
      Biomed Mater Res Part B: Appl Biomater, 2018.

PMID- 30096219
TI  - Tree lizard (Urosaurus ornatus) growth decreases with population density, but
      increases with habitat quality.
AB  - Habitat selection models can explain spatial patterns in the relative abundance
      of animals in different habitats based on the assumption that fitness declines as
      density in a habitat increases. Ectotherms, such as lizards, may not follow
      predictions of density-dependent habitat selection models because temperature,
      which is unaffected by density, strongly influences their habitat selection. If
      competition for limited resources decreases fitness, then crowding should cause a
      decrease in body size and growth rates. We used skeletochronology and body size
      data from tree lizards (Urosaurus ornatus) at six sites that each spanned two
      habitats varying in quality to test the hypothesis that habitat selection is
      density dependent because growth is limited by competition for resources and by
      habitat quality. First, we tested that the maximum body size of lizards decreased
      with higher densities in a habitat by comparing growth between sites. Second, we
      tested whether body size and growth were higher in the habitat with more
      resources by controlling for density in a habitat and comparing growth between
      habitats in different sites. We found evidence of density-dependent growth in
      females, but not in males. Females in more crowded sites reached a smaller
      maximum size. Females in the higher quality habitat also grew larger than females
      in the lower quality habitat after controlling for differences in density between
      the habitats. Therefore, we found partial support for our hypothesis that
      competition for resources limits growth and causes density-dependent habitat
      selection.

PMID- 30096220
TI  - PlncRNA-1 is overexpressed in retinoblastoma and regulates retinoblastoma cell
      proliferation and motility through modulating CBR3.
AB  - PlncRNA-1 has been suggested to function as an oncogenic role in prostate cancer,
      colorectal cancer, hepatocellular carcinoma, esophageal squamous cell carcinoma,
      and gastric cancer. The expression pattern of PlncRNA-1 in retinoblastoma
      remained unknown. Therefore, the aim of this study was to explore the clinical
      significance of PlncRNA-1 in retinoblastoma patient and the biological function
      and molecular mechanism of PlncRNA-1 in regulating retinoblastoma cell
      proliferation, migration, and invasion. The results showed the level of PlncRNA-1
      expression was obviously increased in retinoblastoma tissues and cell lines
      compared with compared with normal retina tissues and retina cell lines,
      respectively. Meanwhile, patients with advanced stage retinoblastoma had higher
      levels of PlncRNA-1 expression than patients with early stage retinoblastoma.
      There was an inverse correlation between PlncRNA-1 expression and CBR3 expression
      in retinoblastoma tissues, and PlncRNA-1 negatively regulated mRNA and protein
      expressions of CBR3. The in vitro experiments showed that down-regulation of
      PlncRNA-1 expression suppressed retinoblastoma cell proliferation, migration and
      invasion through up-regulating CBR3. In conclusion, PlncRNA-1 serves as an
      oncogenic lncRNA in regulating retinoblastoma cell proliferation, migration, and
      invasion through proliferation, migration, and invasion through up-regulating
      CBR3. (c) 2018 IUBMB Life, 70(10):969-975, 2018.

PMID- 30096221
TI  - Characterization of a novel Drosophila melanogaster cis-regulatory module that
      drives gene expression to the larval tracheal system and adult thoracic
      musculature.
AB  - In a previous bioinformatics analysis we identified 10 conserved Drosophila
      melanogaster sequences that reside upstream from protein coding genes (CGs). Here
      we characterize one of these genomic regions, which constitutes a Drosophila
      melanogaster cis-regulatory module (CRM) that we denominate TT-CRM. The TT-CRM is
      646 bp long and is located in one of the introns of CG32239 and resides about
      3,500 bp upstream of CG13711 and about 620 bp upstream of CG12493. Analysis of
      646 bp-lacZ lines revealed that TT-CRM drives gene expression not only to the
      larval, prepupal, and pupal tracheal system but also to the adult dorsal
      longitudinal muscles. The patterns of mRNA expression of the transgene and of the
      CGs that lie in the vicinity of TT-CRM were investigated both in dissected
      trachea and in adult thoraces. Through RT-qPCR we observed that in the tracheal
      system the pattern of expression of 646 bp-lacZ is similar to the pattern of
      expression of CG32239 and CG13711, whereas in the thoracic muscles 646 bp-lacZ
      expression accompanies the expression of CG12493. Together, these results suggest
      new functions for two previously characterized D. melanogaster genes and also
      contribute to the initial characterization of a novel CRM that drives a dynamic
      pattern of expression throughout development.

PMID- 30096222
TI  - A Probabilistic Transmission Model for the Spread of Extended-Spectrum-beta
      Lactamase and AmpC-beta-Lactamase-Producing Escherichia Coli in the Broiler
      Production Chain.
AB  - Direct contact between humans and live broilers, as well as the consumption of
      chicken meat, have been suggested as pathways for transmission of extended
      spectrum-beta-lactamase (ESBL) and AmpC-beta-lactamase (AmpC)-producing
      Escherichia coli. One approach to design intervention strategies to control the
      transmission of such bacteria between animals and humans is to study the
      transmission pathways of such bacteria between the animals themselves. The
      rationale is that controlling the process of the underlying source, here
      transmission between animals, can provide hints on how to control a higher-level
      process, here the transmission between animals and humans. The focus of this
      article is the transmission of the above-mentioned bacteria between broilers and
      broiler flocks in meat production with regards to the establishment of possible
      intervention strategies to reduce the transfer of these bacteria between animals.
      The objective of this work is to design a mathematical transmission model
      describing the effects of vertical and horizontal bacterial transmission in the
      broiler production chain, from the parent generation to the slaughterhouse level.
      To achieve this objective, an existing transmission model for Campylobacter was
      adapted for the case of E. coli. The model keeps track of prevalence among flocks
      (flock prevalence) and of prevalence among animals within one flock (animal
      prevalence). Flock and animal prevalences show different dynamics in the model.
      While flock prevalence increases mainly through horizontal transmission in
      hatcheries, animal prevalence increases mainly at the broiler-fattening farm.
      Transports have rather small effects just as the vertical transmission from
      parents to chicks.

PMID- 30096223
TI  - Brain networks underlying conscious tactile perception of textures as revealed
      using the velvet hand illusion.
AB  - Humans are adept at perceiving textures through touch. Previous neuroimaging
      studies have identified a distributed network of brain regions involved in the
      tactile perception of texture. However, it remains unclear how nodes in this
      network contribute to the tactile awareness of texture. To examine the hypothesis
      that such awareness involves the interaction of the primary somatosensory cortex
      with higher order cortices, we conducted a functional magnetic resonance imaging
      (fMRI) study utilizing the velvet hand illusion, in which an illusory velvet-like
      surface is perceived between the hands. Healthy participants were subjected to a
      strong illusion, a weak illusion, and tactile perception of real velvet. The
      strong illusion induced greater activation in the primary somatosensory cortex
      (S1) than the weak illusion, and increases in such activation were positively
      correlated with the strength of the illusion. Furthermore, both actual and
      illusory perception of velvet induced common activation in S1.
      Psychophysiological interaction (PPI) analysis revealed that the strength of the
      illusion modulated the functional connectivity of S1 with each of the following
      regions: the parietal operculum, superior parietal lobule, precentral gyrus,
      insula, and cerebellum. The present results indicate that S1 is associated with
      the conscious tactile perception of textures, which may be achieved via
      interactions with higher order somatosensory areas.

PMID- 30096224
TI  - Loading Lovastatin into Camptothecin-Floxuridine Conjugate Nanocapsules for
      Enhancing Anti-metastatic Efficacy of Cocktail Chemotherapy on Triple-negative
      Breast Cancer.
AB  - Triple-negative breast cancer (TNBC) is a malignant and refractory disease with
      high morbidity and mortality. The TNBC shows no response to hormonal therapy nor
      targeted therapy due to the lack of known targetable biomarkers. Furthermore, the
      TNBC also exhibits a high degree of heterogeneity that leads to cancer evolution,
      drug resistance, metastatic progression, and recurrence, arising from the tumor
      initiating properties of cancer stem cells (CSCs). Thus, the development of
      radical therapeutic regimens with high efficacy and limited side effects is
      crucial. In this study, we designed an innovative ternary cocktail chemotherapy
      by using Lovastatin (L)-loaded Janus camptothecin-floxuridine conjugate (CF)
      nanocapsules (NCs) with ultrahigh drug loading capacity. The obtained LCF NCs
      were shown to be able to suppress growth of TNBC, including inhibition of growth
      and metastasis of CSCs, both in vitro and in tumor-bearing mice. Moreover, in
      animal experiments, the LCF NCs showed sustained and synchronous drug release
      (half-life > 300 min), 85.2% reduction in pulmonary metastases, and no cancer
      recurrence during one-month observation post-treatment. Thus, this innovative LCF
      NC design provides a simple and synergistic strategy for the development of
      simultaneous triple chemotherapy and could be an efficacious, safe, and amenable
      choice with higher therapeutic relevance and fewer toxic complications than
      conventional multidrug delivery systems for TNBC treatment in the future.

PMID- 30096225
TI  - Alkaline Exchange Polymer Membrane Electrolyte for High Performance of All-Solid
      State Electrochemical Devices.
AB  - As a potential solution to ubiquitous energy concerns, anion-exchange membranes
      (AEMs) have been widely used as the electrolyte in alkaline fuel cells (AFCs),
      and significant refinement of AEMs has been achieved in the past few decades.
      However, it remains unknown whether AEMs can be used as an electrolyte in a solid
      state supercapacitor or zinc-air battery. A low-cost alkaline exchange membrane
      electrolyte composed of chitosan and poly(diallyldimethylammonium chloride) that
      possesses a high OH- conductivity (0.024 S cm-1), strong alkaline stability (216
      h at 8 M KOH), good thermal stability, and low degree of anisotropic swelling,
      was found to provide a high electrochemical performance in all-solid-state
      devices. Prototypes of the solid AFC with the membrane shows superior stability
      over 500 h. The carbon nanotube-based all-solid-state supercapacitor with the
      membrane generated a rectangular cyclic voltammetry curve up to 10 V s-1 and
      excellent cycling stability of 4000 cycles with 84% specific capacitance
      retention. The all-solid-state zinc-air battery demonstrates high power density
      (48.9 mW cm-2). These advantages indicate that the membrane is a promising
      electrolyte for all-solid-state electrochemical devices.

PMID- 30096226
TI  - Self-Assembly of alpha-Helical Polypeptides into Microscopic and Enantiomorphic
      Spirals.
AB  - Helical structures are ubiquitous in biological materials and often serve a
      structural purpose. Bioinspired helical materials can be challenging to
      synthesize and rarely reach the degree of hierarchy of their natural
      counterparts. Here we report the first example of particles synthesized by direct
      emulsification of polypeptides found to display spiral morphologies in the dry
      state. The polypeptides were alpha-helical homo- and copolypeptides of gamma
      benzyl glutamate and allylglycine. The chirality of the spirals was controlled by
      the chirality of the alpha-helices. Notably, right-handed alpha-helical
      polypeptides (rich in l residues) produced clockwise spirals, whereas left-handed
      alpha-helical polypeptides (rich in d residues) produced the enantiomorphs, i.e.,
      counterclockwise spirals. The disruption of the alpha-helical conformation by the
      introduction of chiral defects led to less regular spirals and in some cases
      their suppression. A hypothesis for the transmission of helicity and chirality
      from a molecular to a higher hierarchical level, involving fibril bundling of
      coiled alpha-helices, is proposed.

PMID- 30096227
TI  - Increasing Compound Identification Rates in Untargeted Lipidomics Research with
      Liquid Chromatography Drift Time-Ion Mobility Mass Spectrometry.
AB  - Unknown metabolites represent a bottleneck in untargeted metabolomics research.
      Ion mobility-mass spectrometry (IM-MS) facilitates lipid identification because
      it yields collision cross section (CCS) information that is independent from mass
      or lipophilicity. To date, only a few CCS values are publicly available for
      complex lipids such as phosphatidylcholines, sphingomyelins, or
      triacylglycerides. This scarcity of data limits the use of CCS values as an
      identification parameter that is orthogonal to mass, MS/MS, or retention time. A
      combination of lipid descriptors was used to train five different machine
      learning algorithms for automatic lipid annotations, combining accurate mass ( m/
      z), retention time (RT), CCS values, carbon number, and unsaturation level. Using
      a training data set of 429 true positive lipid annotations from four lipid
      classes, 92.7% correct annotations overall were achieved using internal cross
      validation. The trained prediction model was applied to an unknown milk
      lipidomics data set and allowed for class 3 level annotations of most features
      detected in this application set according to Metabolomics Standards Initiative
      (MSI) reporting guidelines.

PMID- 30096228
TI  - Superior Bactericidal Efficacy of Fucose-Functionalized Silver Nanoparticles
      against Pseudomonas aeruginosa PAO1 and Prevention of Its Colonization on Urinary
      Catheters.
AB  - Pseudomonas aeruginosa, a Gram-negative rod-shaped bacterium is a notorious
      pathogen causing chronic infections. Its ability to form antibiotic-resistant
      biofilm has raised the need for the development of alternative treatment
      approaches. An ideal alternate can be silver nanoparticles known for their strong
      yet tunable bactericidal activity. However, their use in commercial in vivo
      medicine could not see the light of the day because of the unwanted toxicity of
      silver in the host cells at higher concentrations. Thus, strategies which can
      modulate the bacterial cell-silver nanoparticle interactions thereby reducing the
      amount of nanoparticles required to kill a typical number of bacterial cells are
      utmost welcomed. The current work showcases one such strategy by functionalizing
      the silver nanoparticles with l-fucose to increase their interactions with the
      LecB lectins present on P. aeruginosa PAO1. The advantage of this approach lies
      in the higher bactericidal and antibiofilm activity of fucose-functionalized
      silver nanoparticles (FNPs) as compared to the citrate-capped silver
      nanoparticles (CNPs) of similar size and concentrations. The superior
      bactericidal potential of FNPs as demonstrated by fluorescence-assisted cell
      sorting, confocal laser scanning microscopy, and transmission electron microscopy
      analyses may be attributed to the higher reactive oxygen species generation and
      oxidative membrane damage. Additionally, FNPs prevented the formation of biofilms
      by downregulating the expression of various virulence genes at lower
      concentrations as compared to CNPs. The practical applicability of the approach
      was demonstrated by preventing bacterial colonization on artificial silicone
      rubber surfaces. These results can be extrapolated in the treatment of catheter
      associated urinary tract infections caused by P. aeruginosa. In conclusion, the
      present work strongly advocates the use of antivirulence targets and their
      corresponding binding residues for the augmentation of the bactericidal effect of
      silver nanoparticles.

PMID- 30096229
TI  - Characterization of Protein Kinase ULK3 Regulation by Phosphorylation and
      Inhibition by Small Molecule SU6668.
AB  - Serine/threonine protein kinase ULK3 is implicated in a variety of cellular
      processes, including autophagy, cell division, and execution of the Sonic
      hedgehog pathway. However, very little about how its biological activity could be
      controlled is known. This study focuses on unraveling biochemical insights into
      the mechanism of inhibition and activation of ULK3. We identify novel
      phosphorylation sites in ULK3 and show that autophosphorylation has no impact on
      the kinase activity of the protein. We further demonstrate that phosphorylation
      of two residues in the kinase domain of ULK3 by an as yet unidentified kinase may
      completely abolishes its catalytic activity. We show that a low-molecular weight
      inhibitor SU6668, designed as an ATP competitive inhibitor for tyrosine kinases,
      binds in the ATP pocket of ULK3 yet inhibits ULK3 kinase activity in a partially
      ATP noncompetitive manner. Finally, we demonstrate that the ULK3 kinase domain,
      annotated in silico, is not sufficient for its kinase activity, and additional
      amino acids in the 271-300 region are required.

PMID- 30096231
TI  - Exact Density Functional Obtained via the Levy Constrained Search.
AB  - A stochastic minimization method for a real-space wave function, Psi(r1, r2...r
      n), constrained to a chosen density, rho(r), is developed. It enables the
      explicit calculation of the Levy constrained search, F[rho] = minPsi->rho?Psi| T
      + V ee|Psi?, which gives the exact functional of density functional theory. This
      general method is illustrated in the evaluation of F[rho] for densities in one
      dimension with a soft-Coulomb interaction. Additionally, procedures are given to
      determine the first and second functional derivatives, delta F/deltarho(r) and
      delta2 F/[deltarho(r)deltarho(r')]. For a chosen external potential, v(r), the
      functional and its derivatives are used in minimizations over densities to give
      the exact energy, E v, without needing to solve the Schrodinger equation.

PMID- 30096230
TI  - Metabolic Engineering of Escherichia coli for Efficient Production of 2-Pyrone
      4,6-dicarboxylic Acid from Glucose.
AB  - 2-Pyrone-4,6-dicarboxylic acid (PDC) is a pseudoaromatic dicarboxylic acid and is
      a promising biobased building block chemical that can be used to make diverse
      polyesters with novel functionalities. In this study, Escherichia coli was
      metabolically engineered to produce PDC from glucose. First, an efficient
      biosynthetic pathway for PDC production from glucose was suggested by in silico
      metabolic flux simulation. This best pathway employs a single-step biosynthetic
      route to protocatechuic acid (PCA), a metabolic precursor for PDC biosynthesis.
      On the basis of the selected PDC biosynthetic pathway, a shikimate dehydrogenase
      (encoded by aroE)-deficient E. coli strain was engineered by introducing
      heterologous genes of different microbial origin encoding enzymes responsible for
      converting 3-dehydroshikimate (DHS) to PDC, which allowed de novo biosynthesis of
      PDC from glucose. Next, production of PDC was further improved by applying
      stepwise rational metabolic engineering strategies. These include elimination of
      feedback inhibition on 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase
      (encoded by aroG) by overexpressing a feedback-resistant variant, enhancement of
      the precursor phosphoenolpyruvate supply by changing the native promoter of the
      ppsA gene with the strong trc promoter, and reducing accumulation of the major
      byproduct DHS by overexpression of a DHS importer (encoded by shiA). Furthermore,
      cofactor (NADP+/NADPH) utilization was manipulated through genetic modifications
      of the E. coli soluble pyridine nucleotide transhydrogenase (encoded by sthA),
      and the resultant impact on PDC production was investigated. Fed-batch
      fermentation of the final engineered E. coli strain allowed production of 16.72
      g/L of PDC from glucose with the yield and productivity of 0.201 g/g and 0.172
      g/L/h, respectively, representing the highest PDC production performance indices
      reported to date.

PMID- 30096232
TI  - Tailoring Permeability of Microporous Copper Structures through Template
      Sintering.
AB  - Microporous metals are used extensively for applications that combine convective
      and conductive transport and benefit from low resistance to both modes of
      transport. Conventional fabrication methods, such as direct sintering of metallic
      particles, however, often produce structures with limited fluid transport
      properties due to the lack of control over pore morphologies such as the pore
      size and porosity. Here, we demonstrate control and improvement of hydraulic
      permeability of microporous copper structures fabricated using template-assisted
      electrodeposition. Template sintering is shown to modify the fluid transport
      network in a manner that increases permeability by nearly an order of magnitude
      with a less significant decrease (~38%) in thermal conductivity. The measured
      permeabilities range from 4.8 * 10-14 to 1.3 * 10-12 m2 with 5 MUm pores, with
      the peak value being roughly 5 times larger than the published values for
      sintered copper particles of comparable feature sizes. Analysis indicates that
      the enhancement of permeability is limited by constrictions, i.e., bottlenecks
      between connecting pores, whose dimensions are highly sensitive to the sintering
      conditions. We further show contrasting trends in permeability versus
      conductivity of the electrodeposited microporous copper and conventional sintered
      copper particles and suggest these differing trends to be the result of their
      inverse structural relationship.

PMID- 30096233
TI  - SpyTag/SpyCatcher Functionalization of E2 Nanocages with Stimuli-Responsive Z-ELP
      Affinity Domains for Tunable Monoclonal Antibody Binding and Precipitation
      Properties.
AB  - E2 nanocages functionalized with Z-domain-elastin-like polypeptide affinity
      ligands (Z-ELP40) using Sortase A (SrtA) ligation have been shown to be a
      promising scaffold for purifying monoclonal antibodies (mAbs) based on affinity
      precipitation. However, the reversible nature of SrtA reaction has been
      attributed to the low ligation efficiency (<25%) and has significantly limited
      the practical utility of the technology. Here, we reported an improved
      conjugation platform using the SpyTag/SpyCatcher pair to form a spontaneous
      isopeptide bond between SpyTag-E2 and Z-ELP-SpyCatcher fusion proteins of two
      different ELP chain-lengths. Using this system, E2 ligation efficiencies
      exceeding 90% were obtained with both 40- and 80-repeat Z-ELP-SpyCatcher fusions.
      This enabled the production of nanocages fully functionalized with Z-ELP for
      improved aggregation and mAb binding. Compared to the 50% decorated Z-ELP40-E2
      nanocages produced by SrtA ligation, the fully decorated Z-ELP80-Spy-E2 nanocages
      exhibited a 10  degrees C lower transition temperature and a 2-fold higher mAb
      binding capacity. The improved transition property of the longer Z-ELP80 backbone
      allowed for >90% recovery of Z-ELP80-Spy-E2 nanocages at room temperature using
      0.1 M ammonium sulfate after mAb elution. The flexibility of customizing
      different affinity domains onto the SpyTag-E2 scaffold should expand our ability
      to purify other non-mAb target proteins based on affinity precipitation.

PMID- 30096234
TI  - Continuous-Flow Production of Succinic Anhydrides via Catalytic beta-Lactone
      Carbonylation by Co(CO)4?Cr-MIL-101.
AB  - Industrial synthesis of succinic acid relies on hydrocarbon oxidation or biomass
      fermentation routes that suffer from energy-costly separation processes. Here we
      demonstrate an alternate route to succinic anhydrides via beta-lactone
      carbonylation by heterogeneous bimetallic ion-pair catalysis in Co(CO)4-
      incorporated Cr-MIL-101 (Co(CO)4?Cr-MIL-101, Cr-MIL-101 = Cr3O(BDC)3F, H2BDC =
      1,4-benzenedicarboxylic acid). Postsynthetically introduced Co(CO)4- facilitates
      CO insertion to beta-lactone substrates activated by the Lewis acidic Cr(III)
      centers of the metal-organic framework (MOF), leading to catalytic carbonylation
      with activity and selectivity profiles that compare favorably to those reported
      for homogeneous ion-pair catalysts. Moreover, the heterogeneous nature of the MOF
      catalyst enables continuous production of succinic anhydride through a packed bed
      reactor, with room temperature beta-propiolactone carbonylation activity of 1300
      molAnhydride.molCo-1 over 6 h on stream. Simple evaporation of the fully
      converted product stream yields the desired anhydride as isolated solids,
      highlighting the unique processing advantages conferred by this first example of
      heterogeneous beta-lactone carbonylation pathway.

PMID- 30096235
TI  - Assessment of Density Functional Approximations for Highly Correlated Oxides: The
      Case of CeO2 and Ce2O3.
AB  - CeO2 based materials are very attractive as catalytic components for industrial
      processes and environmentally friendly technologies; therefore, a reliable and
      computationally affordable theoretical description of the main properties of
      ceria is needed. In particular, the description of the interconversion between
      the Ce(IV) and Ce(III) oxidation states, on which lies the main chemical features
      of the cerium oxide, results in quite a challenge at the Density Functional
      Theory level. Here, we tested several density functional approximations, spanning
      from GGA to hybrid (Global, Meta-Global, and Range Separated Corrected)
      functionals, on the structural, vibrational, electronic, and thermochemical
      properties of bulk CeO2 and Ce2O3. GGA and Meta-GGA xc best predict the
      thermochemical data, while the discrepancies increase with the introduction of
      the exact exchange in hybrid functionals. Overall, the Short Range Corrected and
      Global Hybrid functionals with a percentage of Exact Exchange between 16 and 25
      give the best description of the crystal properties. Then, a group of the best
      performing functionals has been tested on the formation energy of an oxygen
      vacancy at the (111) CeO2 surface. In general, increasing the amount of exact
      exchange in the hybrid functionals leads to a better description of the localized
      Ce 4 f states, while the energy of formation of the O vacancy decreases,
      worsening compared to the experiment.

PMID- 30096236
TI  - Transcriptomics and iTRAQ-Proteomics Analyses of Bovine Mammary Tissue with
      Streptococcus agalactiae-Induced Mastitis.
AB  - Mastitis is a highly prevalent disease in dairy cows that causes large economic
      losses. Streptococcus agalactiae is a common contagious pathogen and a major
      cause of bovine mastitis. The immune response to intramammary infection with S.
      agalactiae in dairy cows is a very complex biological process. To understand the
      host immune response to S. agalactiae-induced mastitis, mammary gland of
      lactating Chinese Holstein cows was challenged with S. agalactiae via nipple tube
      perfusion. Visual inspection, analysis of milk somatic cell counts,
      histopathology, and transmission electron microscopy of mammary tissue were
      performed to confirm S. agalactiae-induced mastitis. Microarray and isobaric tags
      for relative and absolute quantitation (iTRAQ) were used to compare the
      transcriptomes and proteomes of healthy and mastitic mammary tissue. Compared
      with healthy tissue, a total of 129 differentially expressed genes (DEGs, fold
      change >2, p < 0.05) and 144 differentially expressed proteins (DEPs, fold change
      >1.2, p < 0.05) were identified in mammary tissue from S. agalactiae-challenged
      cows. Among the concordant 18 DEGs/DEPs, immunoglobulin M precursor, cathelicidin
      7 precursor, integrin alpha-5, and complement C4-A-like isoform X1 were
      associated with mastitis. Intramammary infection with S. agalactiae triggered a
      complex host innate immune response that involved complement and coagulation
      cascades, ECM-receptor interaction, focal adhesion, and phagosome and bacterial
      invasion of epithelial cells pathways. These results provide candidate genes or
      proteins for further studies in the context of prevention and targeted treatment
      of bovine mastitis.

PMID- 30096237
TI  - Reduction of Tomato-Plant Chilling Tolerance by CRISPR-Cas9-Mediated SlCBF1
      Mutagenesis.
AB  - Chilling stress is the main constraint in tomato ( Solanum lycopersicum)
      production, as this is a chilling-sensitive horticultural crop. The highly
      conserved C-repeat binding factors (CBFs) are cold-response-system components
      found in many species. In this study, we generated slcbf1 mutants using the
      CRISPR-Cas9 system and investigated the role of SlCBF1 in tomato-plant chilling
      tolerances. The slcbf1 mutants exhibited more severe chilling-injury symptoms
      with higher electrolyte leakage and malondialdehyde levels than wild-type (WT)
      plants. Additionally, slcbf1 mutants showed lower proline and protein contents
      and higher hydrogen peroxide contents and activities of antioxidant enzymes than
      WT plants. Knockout of SlCBF1 significantly increased indole acetic acid contents
      but decreased methyl jasmonate, abscisic acid, and zeatin riboside contents. The
      reduced chilling tolerance of the slcbf1 mutants was further reflected by the
      down-regulation of CBF-related genes. These results contribute to a better
      understanding of the molecular basis underlying SlCBF1 mediation of tomato
      chilling sensitivity.

PMID- 30096238
TI  - Growth of Au-Pd2Sn Nanorods via Galvanic Replacement and Their Catalytic
      Performance on Hydrogenation and Sonogashira Coupling Reactions.
AB  - Colloidal Pd2Sn and Au-Pd2Sn nanorods (NRs) with tuned size were produced by the
      reduction of Pd and Sn salts in the presence of size- and shape-controlling
      agents and the posterior growth of Au tips through a galvanic replacement
      reaction. Pd2Sn and Au-Pd2Sn NRs exhibited high catalytic activity toward quasi
      homogeneous hydrogenation of alkenes (styrene and 1-octene) and alkynes
      (phenylacetylene and 1-octyne) in dichloromethane. Au-Pd2Sn NRs showed higher
      activity than Pd2Sn for 1-octene, 1-octyne, and phenylacetylene. In Au-Pd2Sn
      heterostructures, X-ray photoelectron spectroscopy evidenced an electron donation
      from the Pd2Sn NR to the Au tips. Such heterostructures showed distinct catalytic
      behavior in the hydrogenation of compounds containing a triple bond such as
      tolan. This can be explained by the aurophilicity of triple bonds. To further
      study this effect, Pd2Sn and Au-Pd2Sn NRs were also tested in the Sonogashira
      coupling reaction between iodobenzene and phenylacetylene in N, N
      dimethylformamide. At low concentration, this reaction provided the expected
      product, tolan. However, at high concentration, more reduced products such as
      stilbene and 1,2-diphenylethane were also obtained, even without the addition of
      H2. A mechanism for this unexpected reduction is proposed.

PMID- 30096240
TI  - Presence and Role of Midplane Cholesterol in Lipid Bilayers Containing Registered
      or Antiregistered Phase Domains.
AB  - Three-component lipid mixtures can produce coexisting liquid ordered and liquid
      disordered phases, a model for eukaryotic plasma membrane rafts. In
      compositionally symmetric bilayers with two phase-separated leaflets, phase
      domains of the two leaflets may align through registration, where domains are
      found across from domains of the same phase, or else antiregistration, where
      domains are found across from domains of the opposite phase. This alignment could
      serve as a method of information communication across the plasma membrane. We
      used coarse-grained molecular dynamics simulations to study ternary mixtures of a
      high-melting-temperature phospholipid, a low-melting-temperature phospholipid,
      and cholesterol. We found a significant presence of cholesterol molecules at the
      bilayer midplane rather than in a leaflet in some systems, corresponding to a
      lack of registration. Increasing the length of the acyl chains from 16 to 24
      carbons in high-melting-temperature phospholipids or increasing the concentration
      of cholesterol from 20 to 35 mol % in the bilayer produced a transition from
      registration to antiregistration and gave rise to significant populations of
      midplane cholesterol.

PMID- 30096239
TI  - Enhancement of Exciton-Phonon Scattering from Monolayer to Bilayer WS2.
AB  - Layered transition metal dichalcogenides exhibit the emergence of a direct
      bandgap at the monolayer limit along with pronounced excitonic effects. In these
      materials, interaction with phonons is the dominant mechanism that limits the
      exciton coherence lifetime. Exciton-phonon interaction also facilitates energy
      and momentum relaxation, and influences exciton diffusion under most experimental
      conditions. However, the fundamental changes in the exciton-phonon interaction
      are not well understood as the material undergoes the transition from a direct to
      an indirect bandgap semiconductor. Here, we address this question through optical
      spectroscopy and microscopic theory. In the experiment, we study room-temperature
      statistics of the exciton line width for a large number of mono- and bilayer WS2
      samples. We observe a systematic increase in the room-temperature line width of
      the bilayer compared to the monolayer of 50 meV, corresponding to an additional
      scattering rate of ~0.1 fs-1. We further address both phonon emission and
      absorption processes by examining the temperature dependence of the width of the
      exciton resonances. Using a theoretical approach based on many-body formalism, we
      are able to explain the experimental results and establish a microscopic
      framework for exciton-phonon interactions that can be applied to naturally
      occurring and artificially prepared multilayer structures.

PMID- 30096241
TI  - Graphene-Dendrimer Nanostars for Targeted Macrophage Overexpression of
      Metalloproteinase 9 and Hepatic Fibrosis Precision Therapy.
AB  - Fibrosis contributes to ~45% of all deaths in industrialized nations, but no
      direct antifibrotic therapeutic interventions exist to date. Graphene-based
      nanomaterials exhibit excellent versatility in electronics, and emerging trends
      exploit their properties for biomedical applications, especially for drug and
      gene delivery. We designed constructs of graphene nanostars linked to PAMAM-G5
      dendrimer for the selective targeting and delivery of a plasmid expressing the
      collagenase metalloproteinase 9 under the CD11b promoter into inflammatory
      macrophages in cirrhotic livers. Graphene nanostars preferentially accumulated in
      inflammatory macrophages M1 in less than 3 h in a manner unaffected by covalent
      linkage to dendrimers. Dendrimer-graphene nanostars efficiently delivered the
      plasmid encoding for metalloproteinase 9 into macrophages, allowing the synthesis
      and secretion of the metalloproteinase to digest adjacent collagen fibers. In
      turn, metalloproteinase 9 overexpression promoted the macrophage switch from
      inflammatory M1 to pro-regenerative M2 in 3 days. This targeted gene therapy
      reduced selectively and locally the presence of collagen fibers in fibrotic
      tracts where inflammatory macrophages accumulated in cirrhotic mice without
      affecting the activation state of hepatic stellate cells. Overall, this treatment
      significantly reduced hepatic injury and improved liver restoration in mice with
      liver cirrhosis treated for 10 days. Graphene-dendrimer nanostars targeted the
      macrophage overexpression of metalloproteinase 9, selectively reducing hepatic
      fibrosis, and might be a good treatment for diseases associated with fibrosis and
      inflammatory macrophage accumulation.

PMID- 30096242
TI  - All-Hydrocarbon Staples and Their Effect over Peptide Conformation under
      Different Force Fields.
AB  - Olefinic staples enhance alpha-helical content and conformational stability in
      peptides, maintaining a structural scaffold that allows the emulation of specific
      regions of protein surfaces for therapeutical purposes. The ability to anticipate
      the efficacy of adding a staple to a peptide through computational simulations
      may contribute to lowering the costs associated with rational drug design. We
      evaluated the capabilities of different force fields to reproduce the effect of
      all-hydrocarbon staples in molecular dynamics simulations. Using the AMBER99SB
      ILDN, CHARMM36, and GROMOS54A7 force fields and two distinct initial
      conformations, we compared our results to experimentally obtained circular
      dichroism data. The GROMOS54A7 united-atom force field seems to be more accurate
      compared with all-atom force fields, despite being unable to reproduce the effect
      of the staple in some of the simulated systems. With further force field
      enhancements, MD simulations may be used to anticipate conformational effects of
      all-hydrocarbon staples in peptides.

PMID- 30096244
TI  - Long noncoding RNA NEAT1 promoted the growth of cervical cancer cells via
      sponging miR-9-5p.
AB  - Accumulating evidence has demonstrated that the long non-coding RNAs (lncRNAs)
      participate in the initiation and progression of cancers. In this study, we found
      that the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was
      significantly increased in both cervical cancer tissues and cell lines.
      Overexpression of NEAT1 promoted the proliferation and migration of cervical
      cancer cells. Molecular study uncovered that NEAT1 functioned as competitive
      endogenous RNA (ceRNA) to bind miR-9-5p and suppress the expression of miR-9-5p.
      Consistently, highly expressed NEAT1 attenuated the inhibitory effect of miR-9-5p
      on the expression of PTEN and POU2F1, which were the targets of miR-9-5p. In
      agreement with the negative regulation of NEAT1 on miR-9-5p, restoration of miR-9
      5p inhibited the promotion of NEAT1 on the growth of cervical cancer cells. Taken
      together, these results indicated that NEAT1 played important roles in regulating
      the growth of cervical cancer cells via targeting miR-9-5p. Our findings
      characterized the possible mechanism of NEAT in cervical cancer.

PMID- 30096243
TI  - Effect of Canagliflozin on Urinary Albumin Excretion in Japanese Patients with
      Type 2 Diabetes Mellitus and Microalbuminuria: A Pilot Study.
AB  - BACKGROUND: Albuminuria characterizes the progression of kidney injury. The
      effect of canagliflozin on the excretion of microalbumin was assessed for
      investigating its renoprotective potential in Japanese patients with type 2
      diabetes mellitus (T2DM). PATIENTS AND METHODS: Twenty Japanese patients with
      T2DM and microalbuminuria were enrolled and administered with 100 mg of
      canagliflozin once a day for 12 weeks. These subjects were admitted to the clinic
      at the start and end of the treatment period for 24-h urine collection. The
      primary endpoint was the percentage change in geometric mean 24-h urinary albumin
      excretion from baseline to week 12. RESULTS: The urinary albumin level decreased
      by 42.0% (95% confidence interval: 21.9-57.0; P = 0.0011) after 12 weeks of
      canagliflozin treatment. A number of blood and urinary parameters also
      significantly decreased, including hemoglobin A1c, fasting plasma glucose,
      estimated glomerular filtration rate, and creatinine clearance, while hematocrit
      was elevated. Among the biomarkers associated with kidney injury and
      inflammation, the urinary level of the oxidative stress marker 8-hydroxy-2'
      deoxyguanosine was also decreased. There were no meaningful correlations noted
      between changes in urinary albumin excretion and other parameters/biomarkers. No
      severe adverse events were reported over the 12-week treatment period.
      CONCLUSIONS: The results of this study indicate that canagliflozin decreases
      microalbuminuria in Japanese patients with T2DM. Albuminuria could be reduced as
      a result of changes in various physiological pathways; therefore, it is
      imperative that future, large-scale, studies attempt to determine the detailed
      mechanisms involved. Canagliflozin may offer a novel therapeutic option for
      Japanese patients with T2DM and incipient nephropathy.

PMID- 30096245
TI  - Effect of video game playing and a glucose preload on subjective appetite,
      subjective emotions, and food intake in overweight and obese boys.
AB  - Video game playing (VGP) is associated with overweight/obesity (OW/OB). VGP and
      caloric preloads in the pre-meal environment influence short-term food intake
      (FI) in healthy weight children. Therefore, the purpose of the present study was
      to examine the effect of pre-meal VGP and a glucose preload on subjective
      emotions, subjective appetite, and FI in boys with OW/OB. On four separate
      mornings, boys with OW/OB (n = 22; mean+/-SD: age = 11.9+/-1.6 years; BMI
      percentile = 94.3+/-3.9) participated in four test conditions. Two hours after a
      standardized breakfast, boys consumed equally sweetened preloads (250 mL) of
      sucralose (0 kcal) or glucose (200 kcal), with or without 30 min of subsequent
      VGP. FI from an ad libitum pizza meal was measured immediately after all test
      conditions. Subjective appetite was measured at 0 (baseline), 15, and 30 min.
      Subjective emotions (aggression, anger, excitement, disappointment, happiness,
      upset, and frustration) were measured at 0 and 30 min. VGP did not affect FI, but
      the glucose preload decreased FI compared with the sucralose control (? = -103+/
      48 kcal, p < 0.01). However, cumulative FI (preload kcal + meal kcal) was 9%
      higher after the glucose preload (p < 0.01). Subjective appetite increased with
      time (p < 0.05) but was not influenced by preload or VGP. Frustration was the
      only subjective emotion that increased following VGP (p < 0.01). A glucose
      preload, but not VGP, suppressed FI in boys with OW/OB, suggesting a primary role
      of physiological factors in short-term FI regulation.

PMID- 30096246
TI  - Pandemic Influenza Readiness Report on Laboratory and Epidemiology Capacity
      United States and Territories, 2015.
AB  - Laboratory and epidemiologic data are vital to identify a novel influenza A virus
      and inform the public health response, whether it be to a localized outbreak or
      pandemic. The Centers for Disease Control and Prevention (CDC) developed the
      Pandemic Influenza Readiness Assessment (PIRA) to evaluate the state of the
      nation's preparedness for the next influenza pandemic. Representatives from all
      62 Public Health Emergency Preparedness (PHEP) awardee jurisdictions were
      requested to complete the web-based questionnaire in July 2015. The PIRA consists
      of 7 modules covering key components of pandemic preparedness; this article
      summarizes results from the laboratory and epidemiology modules. Many of the
      jurisdictions reported they had the capacity to fulfill most of the laboratory
      and epidemiology tasks, including the ability to differentiate novel influenza A
      viruses from seasonal influenza viruses and electronically transfer laboratory,
      surveillance, and case investigation data. Pandemic preparedness includes
      transfer of electronic death records and conducting surveillance for influenza
      associated mortality in adults. Although most jurisdictions self-reported that
      they had the epidemiologic and laboratory capabilities that were assessed,
      additional planning and technical assistance are needed to ensure all states and
      territories have and maintain all critical capacities. The results from this PIRA
      can inform how CDC and federal partners focus future training and outreach.

PMID- 30096247
TI  - Distinguishing Respiratory Features of Category A/B Potential Bioterrorism Agents
      from Community-Acquired Pneumonia.
AB  - Differentiating between illness caused by community-acquired respiratory
      pathogens versus infection by biothreat agents is a challenge. This review
      highlights respiratory and clinical features of category A and B potential
      biothreat agents that have respiratory features as their primary presenting signs
      and symptoms. Recent world events make such a reminder that the possibility of
      rare diseases and unlikely events can occur timely for clinicians, policymakers,
      and public health authorities. Despite some distinguishing features, nothing can
      replace good clinical acumen and a strong index of suspicion in the diagnosis of
      uncommon infectious diseases.

PMID- 30096248
TI  - Long non-coding RNA H19, and not microRNA miR-326, is over-expressed and predicts
      survival in glioblastoma.
AB  - Glioblastoma (GB) represents the most common malignant brain tumor, which,
      despite extensive research, remains of poor prognosis. The focus of recent
      studies of GB pathogenesis has shifted to the study of the role of noncoding RNAs
      (ncRNAs). In this study, we examined the expression levels of the microRNA miR
      326 and the long ncRNA H19 (on which a miR-326 putative binding site was found by
      in silico analysis) in brain tumor tissue from GB patients as compared to cancer
      free brain tissue. Relative expression levels of miR-326 were not found to be
      significantly altered in GB patients. On the contrary, H19 was consistently over
      expressed in all GB patients (p < 0.001), and was correlated with poorer overall
      survival (OS) and progression-free survival (PFS) (p = 0.026 and p = 0.045,
      respectively). At a cutoff value of 5.27, H19 upregulation could predict OS in GB
      patients, with a 71.4% sensitivity and 59.6% specificity (p = 0.026). The current
      GB patients were clustered by the multivariate analysis into four groups based on
      miR-326 and H19 expression profiles, age at diagnosis, and PFS. Our data suggest
      a role for H19 in the pathogenesis of GB and could be a potential prognostic
      biomarker for GB.

PMID- 30096249
TI  - Acute ibuprofen ingestion does not attenuate fatigue during maximal intermittent
      knee extensor or all-out cycling exercise.
AB  - PURPOSE: Recent research suggests that acute consumption of pharmacological
      analgesics can improve exercise performance, but the ergogenic potential of
      ibuprofen (IBP) administration is poorly understood. This study tested the
      hypothesis that IBP administration would enhance maximal exercise performance.
      METHODS: In one study, 13 physically active males completed 60 * 3-s maximum
      voluntary contractions (MVC) of the knee extensors interspersed with a 2-s
      passive recovery period, on two occasions, with the critical torque (CT)
      estimated as the mean torque over the last 12 contractions (part A). In another
      study, 16 active males completed two 3-min all-out tests against a fixed
      resistance on an electrically-braked cycle ergometer with the critical power (CP)
      estimated from the mean power output over the final 30-s of the test (part B).
      All tests were completed 60 min after ingesting maltodextrin (placebo, PL) or 400
      mg of IBP. Peripheral nerve stimulation was administered at regular intervals and
      electromyography was measured throughout. RESULTS: For part A, mean torque (IBP:
      60+/-12 vs. PL: 58+/-14% of pre-exercise MVC) and CT (IBP: 40+/-15 vs. PL: 41+/
      16% of pre-exercise MVC) were not different between conditions (P>0.05). For part
      B, end-test power output (IBP: 292+/-28 W vs PL: 288+/-31 W) and work done (IBP:
      65.9+/-5.9kJ vs PL: 65.4+/-6.4kJ) during the 3-min all-out cycling tests were not
      different between conditions (all P>0.05). For both studies, neuromuscular
      fatigue declined at a similar rate in both conditions (P>0.05). CONCLUSION: Acute
      ingestion of 400 mg IBP does not improve single-leg or maximal cycling
      performance in healthy humans.

PMID- 30096250
TI  - Association of Desmin Gene Variant rs1058261 with Cardiovascular Disease, the
      TAMRISK Study.
AB  - AIMS: Since desmin expression is diminished in vascular smooth muscle cells
      during reparative processes, we wanted to study whether a common intragenic
      single nucleotide polymorphism at nucleotide position 828 (rs1058261) of the DES
      gene associates with hypertension, cerebrovascular complications, and all
      cardiovascular events in the Tampere adult population cardiovascular risk
      (TAMRISK) study. MATERIALS AND METHODS: A Finnish periodic health examination
      cohort of 336 subjects with diagnosed hypertension and 473 controls were
      analyzed. Samples were genotyped for polymorphism using TaqMan techniques.
      Prevalence of ischemic heart diseases, incidence of cerebrovascular diseases, and
      transient cerebral ischemic attacks (TIAs) were obtained by self-report and the
      National Hospital Discharge Registry (HILMO). RESULTS: There was no association
      of any of the rs1058261 genotypes with hypertension at the age of 50. When the
      subjects were followed to the age of 60, after adjustment for gender and body
      mass index, subjects with the genotype CC had higher incidence of cerebrovascular
      events (cerebrovascular diseases and TIA) (4.1%) compared with the T allele
      (1.6%) (p = 0.046). In addition, those with CC genotype had a higher incidence of
      all combined cardiovascular events (12.8%) compared with subjects with the T
      allele (8.5%) (p = 0.028). CONCLUSIONS: Our findings suggest that variations in
      the DES gene may be involved in cardiovascular disease.

PMID- 30096251
TI  - Global Health Security Agenda Implementation: A Case for Community Engagement.
AB  - In today's interconnected world, infectious diseases can spread rapidly within
      and between countries. The 2014-2016 Ebola epidemic in Guinea, Liberia, and
      Sierra Leone underscored the inability of countries with limited capacities and
      weak public health systems to respond effectively to outbreaks. To mitigate
      future health threats, nations and international organizations launched the
      Global Health Security Agenda (GHSA) to accelerate compliance with the WHO's
      International Health Regulations, so as to enhance global protection from
      infectious disease threats. To advance GHSA's mandate to build capacity to
      prevent, detect, and respond to infectious diseases, and thereby contain threats
      at their source, community engagement is needed. This article advocates for
      community engagement in GHSA implementation, using examples from 3 GHSA action
      packages. A country's ability to prevent a local disease outbreak from becoming
      an epidemic often rests with the level of knowledge about the situation and the
      actions taken at the community level.

PMID- 30096252
TI  - A Framework to Guide Economic Analysis of Advance Care Planning.
AB  - BACKGROUND: Advance care planning (ACP) is fundamental to guiding medical care at
      the end of life. Understanding the economic impact of ACP is critical to
      implementation, but most economic evaluations of ACP focus on only a few actors,
      such as hospitals. OBJECTIVE: To develop a framework for understanding and
      quantifying the economic effects of ACP, particularly its distributional
      consequences, for use in economic evaluations. DESIGN: Literature review of
      economic analyses of ACP and related costs to estimate magnitude and direction of
      costs and benefits for each actor and how data on these costs and benefits could
      be obtained or estimated. RESULTS: ACP can lead to more efficient allocation of
      resources by reducing low-value care and reallocating resources to high-value
      care, and can increase welfare by aligning care to patient preferences. This
      economic framework considers the costs and benefits of ACP that accrue to or are
      borne by six actors: the patient, the patient's family and caregivers, healthcare
      providers, acute care settings, subacute and home care settings, and payers.
      Program implementation costs and nonhealthcare costs, such as time costs borne by
      patients and caregivers, are included. Findings suggest that out-of-pocket costs
      for patients and families will likely change if subacute or home care is
      substituted for acute care, and subacute care utilization is likely to increase
      while primary healthcare providers and acute care settings may experience
      heterogeneous effects. CONCLUSIONS: A comprehensive economic evaluation of ACP
      should consider how costs and benefits accrue to different actors.

PMID- 30096253
TI  - Plant Stature Related receptor-like Kinanse2 (PSRK2) acts as a factor that
      determines stem elongation toward gibberellins response in rice.
AB  - Gibberellins (GAs) are a family of plant hormones that are important to multiple
      aspects of plant growth and development, especially stem elongation. A PSRK2 was
      obtained through screening and identifying RLK dominant negative mutants.
      Phenotype of the loss-of-function mutants, psrk2-DN and psrk2-RNAi, showed that
      PSRK2 could influence the length of the uppermost and fourth internodes,
      indicating that PSRK2 might regulate cell division in the intercalary meristems
      and/or cell elongation in the internodes. Moreover, the expression pattern showed
      that PSRK2 was strongly expressed in the joined-nodes after the start-up of
      reproductive growth, but undetectable in leaves. PSRK2 expression was also found
      to be induced by GA3, and PSRK2 was involved in GA signaling in cereal aleurone
      cells, and PSRK2 influence the relative length of the second leaf sheaths in
      seedling stage. These results indicate PSRK2 is a component of GA signaling
      pathway that controls stem elongation by negatively regulating GA responses.
      Abbreviations: Os: Oryza sativa; At: Arabidopsis thaliana; RNAi: RNA interfere;
      DN: Dominate Negative; SMART: Simple Modular Architecture Research Tool; Uni :
      Uniconazol; PSRK2: Plant Stature Related receptor-like Kinase 2; RLK: Receptor
      like Kinase; GA: Gibberellin; IAA: indole-3-acetic acid; BL: Brassinosteroid.

PMID- 30096254
TI  - Balancing Hope and Risk Among Adolescent and Young Adult Cancer Patients with
      Late-Stage Cancer: A Qualitative Interview Study.
AB  - PURPOSE: Previous studies have called for further research to explore adolescent
      and young adult (AYA) decision-making in the context of advanced cancer to
      understand the perspectives of this understudied population. We conducted a
      qualitative study with patients and providers to better understand the decision
      making experience of AYA patients with advanced stages of cancer. METHODS:
      Semistructured qualitative telephone interviews were conducted from April 2016 to
      October 2016. English-speaking AYAs and healthcare providers were recruited
      through the social media sites Twitter and Facebook. AYAs were eligible if they
      were aged 18-39 years at diagnosis and self-reported having metastatic cancer;
      any provider who worked with AYAs with metastatic cancer was eligible.
      Researchers with expertise in qualitative methods conducted inductive thematic
      content analysis of transcribed interviews. The analyzed data were used to
      formulate recommendations for clinicians. RESULTS: Twelve AYA patients with self
      reported stage IV cancer and five clinicians who care for AYAs with advanced
      stages of cancer were enrolled and shared their experience about AYA medical
      decision-making. Four primary themes emerged: (1) AYAs describe receiving unclear
      prognosis, (2) AYAs balance concepts of hope and risk, (3) AYAs choose aggressive
      treatment options, and (4) AYAs want support facing mortality. Recommendations
      for clinicians include clear communication about prognosis and side effects and
      concerted efforts to elicit patient values. CONCLUSION: AYA patients and
      clinicians provided insights into the experiences and decision-making processes
      of AYA patients choosing to continue or discontinue treatment and into the areas
      for improvement in patient-centered oncology care. Taken together, these data
      provide important suggestions for clinicians caring for this vulnerable
      population.

PMID- 30096255
TI  - Media Exchange Performance Test Using the Bradford Assay in an Automated
      Bioreactor Engineering Model for Space Experiments.
AB  - Life science research has been actively carried out in space for a long time
      using bioreactor equipment, in anticipation of manned space exploration and space
      tourism. Such studies have reported that the microgravity environment has a
      negative effect on the human body, including the musculoskeletal system, nervous
      system, and endocrine system. Bone loss and muscular atrophy are issues that need
      to be resolved before long-term exposure of the human body to a space
      environment. To address this problem, Y. K. Kim et al. designed a system in 2015
      and performed an evaluation of an automated bioreactor development model (DM) for
      space experiments. In this study, we developed an automated bioreactor
      engineering model (EM) based on the previous literature, and conducted media
      exchange performance testing using the Bradford assay. We used a novel method
      that allowed quantitative assessment of the media exchange rate versus the
      conventional assessment method using visual observation with a camera. By
      measuring the media exchange rate of the automated bioreactor EM, we attempted to
      verify applicability for the system for space experiments. We expect that the
      experimental method proposed in this study is useful for logical determination of
      liquid exchange or circulation in different closed systems.

PMID- 30096256
TI  - Smart Card Decontamination in a High-Containment Laboratory.
AB  - Validated procedures for decontamination of laboratory surfaces and equipment are
      essential to biosafety and biorisk programs at high-containment laboratories.
      Each high-containment laboratory contains a unique combination of surfaces,
      procedures, and biological agents that require decontamination methods tailored
      to specific facility practices. The Plum Island Animal Disease Center (PIADC) is
      a high-containment laboratory operating multiple biosafety level (BSL)-3, ABSL-3,
      and BSL-3 Ag spaces. The PIADC facility requires the use of federally issued
      smart cards, called personal identity verification (PIV) cards, to access
      information technology (IT) networks both outside and within the high-containment
      laboratory. Because PIV cards may require transit from the BSL-3 to office
      spaces, a validated procedure for disinfecting PIV card surfaces prior to removal
      from the laboratory is critical to ensure biosafety and biosecurity. Two high
      risk select agents used in the PIADC high-containment laboratory are foot-and
      mouth disease virus (FMDV) and swine vesicular disease virus (SVDV). We evaluated
      disinfection of PIV cards intentionally spotted with FMDV and SVDV using a
      modified quantitative carrier test and the liquid chemical disinfectant Virkon(r)
      S. Our experimental design modeled a worst-case scenario of PIV card
      contamination and disinfection by combining high concentrations of virus dried
      with an organic soil load and use of aged Virkon(r) S prepared in hard water.
      Results showed that FMDV and SVDV dried on PIV card surfaces were completely
      inactivated after immersion for 30 and 60 seconds, respectively, in a 5-day-old
      solution of 1% Virkon(r) S. Therefore, this study provided internal validation of
      PIADC biosafety protocols by demonstrating the efficacy of Virkon(r) S to
      inactivate viruses on contaminated smart cards at short contact times.

PMID- 30096257
TI  - Molecular Epidemiological Characterization of Methicillin-Susceptible and 
      Resistant Staphylococcus aureus Isolated from Skin and Soft Tissue Infections in
      Bangladesh.
AB  - Genetic background and molecular characteristics of Staphylococcus aureus
      collected from patients with skin and soft tissue infections were studied in the
      North-Central region of Bangladesh from 2015 to 2016. Among 430 clinical
      isolates, methicillin-resistant S. aureus (MRSA) accounted for 31% having SCCmec
      type IV (73%) and V (14%), and belonged mostly to coagulase (coa) genotypes IIa,
      IIIa, IVb, and XIa, while dominant coa type in methicillin-susceptible S. aureus
      (MSSA) was IIIa, followed by Va, IIa, and VIa. Panton-Valentine Leukocidin genes
      (pvl) were detected at higher rate in MSSA (54%) than in MRSA (24%). Based on
      multilocus sequence typing, pvl-positive MRSA isolates were classified into
      clonal complex 88 (CC88) (ST88, ST2884, ST4345), CC6 (ST6, ST4350), and CC1 (ST1,
      ST772), while pvl-negative MRSA into CC5, CC22, CC80, CC121, and CC672. The pvl
      negative ST80 MRSA isolates had SCCmec-IVa (agr-III/coa-XIc, etd/edinB-positive,
      fusB-negative), indicating that they belong to the novel CC80 clade related to
      the European community-acquired MRSA clone. Among MSSA, genotypes ST121/spa
      t645/coa-Va and ST2884 (CC88)/spa-t2393/coa-IIIa were identified in both pvl
      positive and negative isolates, and all the ST772 isolates harbored pvl. All the
      ST121 isolates had a variant of elastin-binding protein gene (ebpS-v) with
      internal 180-nucleotide deletion. The present study suggested that CC88 (ST88,
      ST2884) and ST772 are the putative dominant lineages of pvl-positive MRSA/MSSA,
      while novel CC80 clade is one of the main pvl-negative MRSA lineages distributed
      endemically in Bangladesh.

PMID- 30096259
TI  - Cardiopulmonary Resuscitation with Extracorporeal Membrane Oxygenation in a
      Patient with Profound Accidental Hypothermia and Refractory Ventricular
      Fibrillation.
AB  - We describe a patient with severe accidental hypothermia (<=25.4 degrees C) and
      prolonged refractory ventricular fibrillation, lasting at least 4 hours and 8
      minutes, who underwent cardiopulmonary resuscitation with extracorporeal membrane
      oxygenation and survived without neurologic deficit.

PMID- 30096258
TI  - Dynamic demethylation of the IL2RA promoter during in vitro CD4+ T cell
      activation in association with IL2RA expression.
AB  - IL2RA, a subunit of the high affinity receptor for interleukin-2 (IL2), plays a
      crucial role in immune homeostasis. Notably, IL2RA expression is induced in CD4+
      T cells in response to various stimuli and is constitutive in regulatory T cells
      (Tregs). We selected for our study 18 CpGs located within cognate regulatory
      regions of the IL2RA locus and characterized their methylation in naive,
      regulatory, and memory CD4+ T cells. We found that 5/18 CpGs (notably CpG + 3502)
      show dynamic, active demethylation during the in vitro activation of naive CD4+ T
      cells. Demethylation of these CpGs correlates with appearance of IL2RA protein at
      the cell surface. We found no influence of cis located SNP alleles upon CpG
      methylation. Treg cells show constitutive demethylation at all studied CpGs.
      Methylation of 9/18 CpGs, including CpG +3502, decreases with age. Our data thus
      identify CpG +3502 and a few other CpGs at the IL2RA locus as coordinated
      epigenetic regulators of IL2RA expression in CD4+ T cells. This may contribute to
      unravel how the IL2RA locus can be involved in immune physiology and pathology.

PMID- 30096260
TI  - Heterologous expression of geraniol dehydrogenase for identifying the metabolic
      pathways involved in the biotransformation of citral by Acinetobacter sp. Tol 5.
AB  - The biotransformation of citral, an industrially important monoterpenoid, has
      been extensively studied using many microbial biocatalysts. However, the
      metabolic pathways involved in its biotransformation are still unclear, because
      citral is a mixture of the trans-isomer geranial and the cis-isomer neral. Here,
      we applied the heterologous expression of geoA, a gene encoding geraniol
      dehydrogenase that specifically converts geraniol to geranial and nerol to neral,
      to identify the metabolic pathways involved in the biotransformation of citral.
      Acinetobacter sp. Tol 5 was employed in order to demonstrate the utility of this
      methodology. Tol 5 transformed citral to (1R,3R,4R)-1-methyl-4-(1-methylethenyl)
      1,3-cyclohexanediol and geranic acid. Biotransformation of citral precursors
      (geraniol and nerol) by Tol 5 transformant cells expressing geoA revealed that
      these compounds were transformed specifically from geranial. Our methodology is
      expected to facilitate a better understanding of the metabolic pathways involved
      in the biotransformation of substrates that are unstable and include geometric
      isomers.

PMID- 30096261
TI  - Heart Transplant Recipients Prefer a Telemental Health Cognitive-Behavioral
      Therapy Intervention Delivered by Telephone.
AB  - BACKGROUND: Depression and anxiety are common after heart transplant, and in a
      regional heart transplant center servicing northern California, willingness to
      participate in treatment can be a major barrier. INTRODUCTION: Our primary aim is
      to design a remote cognitive-behavioral therapy (CBT) intervention. This study is
      the first step in the process. Through a survey to the cohort of heart transplant
      recipients (N = 230), managed within the Kaiser Permanente Northern California's
      Heart Transplant Service, we aimed to assess symptoms of stress, depression, and
      anxiety, patient willingness to participate in a CBT intervention, and preference
      between video and telephone. We proposed to patients a five-visit intervention,
      with the first and last visits in person and the three middle visits by video.
      MATERIALS AND METHODS: One hundred twenty of 230 heart transplant recipients
      returned the 12-question Likert-like survey. Statistical tests included chi
      square, fisher exact test, t-tests, and a logistic regression model. RESULTS:
      Patients who reported two or more symptoms of stress, depression, and anxiety
      were 5.67 times more likely to engage in a remote CBT intervention (odds ratio =
      5.67; 95% confidence interval 1.63-19.78; p = 0.006). Patients experiencing
      stress with depression were the most willing group to participate in a CBT
      intervention. The 12 patients who met the study criteria of 3 years post
      transplant and experiencing at least one mental health symptom were invited to
      participate in the CBT intervention. All patients (12) who met the CBT
      intervention criteria were not willing to participate in the two in-person
      visits. All were willing to participate in a telephone-only CBT intervention.
      DISCUSSION: Among the heart transplant recipients in this cohort, there is more
      willingness to participate in a CBT intervention when distress is higher and
      there is a preference for telephone visits as the modality for treatment
      delivery. CONCLUSIONS: Based on the findings, the CBT intervention will be
      shorter in duration; instead of five visits, there will be four visits; and it
      will be conducted by telephone only. The new intervention will be tested with 8
      to 10 patients, changed, and then it will need to be empirically tested.

PMID- 30096262
TI  - Unique Uses of Cooling Strategies.

PMID- 30096263
TI  - Promising Antituberculosis Activity of Piperine Combined with Antimicrobials: A
      Systematic Review.
AB  - Piperine, a bioactive compound from Piper nigrum and Piper longum, has shown
      promising activity as efflux pump (EP) inhibitor and as adjunct in treatment of
      tuberculosis (TB). The present systematic review investigated scientific studies
      of the activity of piperine against mycobacteria, with a focus on its mechanism
      of action, drug interactions, and antimycobacterial activity. A broad and
      rigorous literature search of three electronic databases (PubMed, Web of
      Knowledge, and LILACS) was performed according to the PRISMA statement. We
      considered studies that were published up to December 1, 2017. Google Scholar was
      also searched to increase the number of publications. We searched for articles
      using the search terms "piperine" and "Mycobacterium spp." The search yielded a
      total of 225 articles. After removing duplicate publications, 208 publications
      remained. Of these, we evaluated the full text of 13 articles. After applying the
      inclusion criteria, eight studies were included in the present systematic review.
      The results of the systematic review showed that piperine has promising anti-TB
      activity, mainly when combined with antimicrobials, and plays an important role
      as an EP inhibitor.

PMID- 30096264
TI  - Evaluation of Root Canal Anatomy of Maxillary Premolars Using Swept-Source
      Optical Coherence Tomography in Comparison with Dental Operating Microscope and
      Cone Beam Computed Tomography.
AB  - OBJECTIVE: This study aimed to evaluate the ability of swept-source optical
      coherence tomography (OCT) to detect internal anatomy of maxillary premolars in
      comparison with dental operating microscope (DOM) and cone beam computed
      tomography (CBCT). BACKGROUND DATA: The ability of OCT to observe the pulp horn
      during cavity preparation and assess the remaining dentin thickness (RDT) has
      been demonstrated, whereas validation of OCT in comparison with other imaging
      techniques seems required. METHODS: Ten extracted human maxillary premolars were
      sectioned perpendicular to the tooth axis from the occlusal surface at
      approximately 2 mm increments. OCT and DOM were performed after each cut, and
      microfocus X-ray computed tomography (micro-CT; reference standard) and CBCT were
      conducted before sectioning and after the first and second cuts. Three examiners
      evaluated all images for presence of the pulp horn/pulp chamber, isthmus, lateral
      canals, and the number of root canals. RDT was determined from OCT, micro-CT, and
      CBCT images. Correlations were analyzed with Pearson's correlation coefficient.
      RESULTS: OCT had a sensitivity and specificity of 0.90 and 0.80 in detecting the
      pulp horn/pulp chamber and 0.84 and 0.71 in detecting the isthmus, respectively.
      The three techniques showed strong correlations in detecting the number of root
      canals compared with micro-CT. OCT and DOM did not detect lateral canals. For RDT
      values, strong correlations were observed between micro-CT and CBCT, micro-CT and
      OCT, and CBCT and OCT (p < 0.01 for all). CONCLUSIONS: Under the present
      experimental condition, OCT accurately measured RDT and detected internal tooth
      anatomy such as the pulp horn, isthmus, and root canals.

PMID- 30096265
TI  - Change of Tinnitus with Xenon Phototherapy of the Stellate Ganglion.
AB  - OBJECTIVE: To develop a treatment for tinnitus called xenon phototherapy of the
      stellate ganglion (XPSG) and analyze its effect on tinnitus. METHODS: Patients
      with chronic tinnitus received XPSG. Symptoms were assessed subjectively with
      tinnitus handicap inventory (THI) and numerical rating scale (NRS). THI and NRS
      scores were analyzed in XPSG (n = 43) and sham treatment (non-XPSG) (n = 18)
      groups. RESULTS: THI and NRS scores improved significantly after 3 months of
      XPSG. Severe cases with high THI or NRS score showed greater improvement. No
      significant difference was observed between before and after sham treatment in
      non-XPSG groups. CONCLUSIONS: XPSG significantly improved THI and NRS scores with
      high patient satisfaction.

PMID- 30096266
TI  - Joint Statement by the Surgery Journal Editors Group: Adopted by Surgical
      Infections.

PMID- 30096267
TI  - Engaging in Weight Loss Tasks of Mobile Health Applications: The Dual Influence
      of Social Support and Body Condition.
AB  - INTRODUCTION: In the past decades, the average weight of residents has increased
      significantly. Weight management has become an important issue in our society.
      With the developments of mobile technology and applications, mobile health
      applications (m-health apps) provide a convenient platform for users to engage in
      weight loss tasks and control their body weight. However, due to the lack of
      proper motivators, engaging in weight loss tasks on m-health apps is stressful
      for the users. The aim of this study is to understand why users engage in weight
      loss tasks, and to be specific, we establish an empirical model to examine the
      effects of social motivators (social support) and personal motivators (body
      condition) and their interactive relationship on the level of user engagement
      using self-determination theory. MATERIALS AND METHODS: We developed a JAVA
      software program and automatically downloaded 1,138 users' information from an m
      health app. Following, we used these data to calculate variables of our research
      model, including body mass index (BMI), informational support, emotional support,
      and the level of engagement in weight loss tasks. Additionally, we used the
      Ordinary Least Squares to estimate our research model. We also checked the
      robustness of the results by dividing the data into different groups. RESULTS:
      The empirical results of our research model indicate that informational and
      emotional supports are positively associated with the engagement levels of users
      in weight loss tasks. Additionally, we have found out that body condition (using
      BMI as a proxy) has a U-shaped relationship effect on users' engagement.
      Furthermore, our research proves that body condition and informational support
      have a substitutive relationship in affecting user engagement. CONCLUSIONS: These
      findings can contribute to the literature concerning online weight loss and to
      provide suggestions for users and practitioners of m-health apps, catering
      different incentive mechanisms to users with different body condition to help
      them control their body weight.

PMID- 30096268
TI  - A Novel Protein Testing Model to Assay the Efficacy of Multiple Irrigation
      Activation Techniques for Removal of Ex Vivo Biomolecular Film.
AB  - OBJECTIVE: This study aimed to compare the debris removal efficacies of
      irrigation activation techniques using ex vivo biomolecular film. MATERIALS AND
      METHODS: Root canals of 50 human mandibular premolars were prepared, and freshly
      prepared collagen solutions were applied into the root canals using a peristaltic
      pump. Specimens were randomly divided into the five groups and irrigated with 3
      mL of 5.25% sodium hypochlorite (NaOCl): G1 (needle irrigation and control
      group): a 27-gauge notched-tip irrigation needle (Endo-Eze; Ultradent, South
      Jordan, UT); G2, Vibringe sonic irrigation system (VSS) (Vibringe B.V. Corp.,
      Amsterdam, Netherlands); G3, EndoActivator sonic irrigation system (EA) (Dentsply
      Tulsa Dental Specialties, Tulsa, OK); G4, passive ultrasonic irrigation (PUI)
      (EMS, Nyon, Sweden); and G5, photon-induced photoacoustic streaming (PIPS)
      (Fotona, Ljubljana, Slovenia). Postirrigation solution was collected in beakers
      containing 3% sodium thiosulfate by which NaOCl solution was neutralized.
      Residual protein levels in NaOCl solution were evaluated by the Bradford method.
      Data were analyzed using ANOVA with Duncan post hoc tests (alpha = 0.05).
      RESULTS: PIPS (laser-activated irrigation) method removed more artificial
      collagen than other experimental groups (EA, PUI, VSS) or the control group (p <=
      0.05). There were no statistical differences among the EA, PUI, and VSS groups.
      The PIPS, PUI, and EA groups were superior compared with the conventional
      irrigation (p <= 0.05); however, there were no significant differences between
      VSS and the conventional irrigation groups. CONCLUSIONS: Although all the methods
      and techniques examined in this study were suitable in extruding the ex vivo
      biomolecular film, the PIPS method was found significantly more effective than
      all the other tested groups (p <= 0.05).

PMID- 30096269
TI  - Characterization of Skeletal Muscle Strain Lesion Induced by Stretching in Rats:
      Effects of Laser Photobiomodulation.
AB  - BACKGROUND: Unusual and exhaustive physical exercise can lead to muscle lesions
      depending on the type of contraction, intensity, duration, age, and level of
      conditioning. Different therapies have been proposed to prevent or reduce
      exercise-induced muscle damage. OBJECTIVE: In this study, we investigate the
      effects of low-level laser therapy on skeletal muscle strain in an experimental
      model in rats. MATERIALS AND METHODS: Male Wistar rats (200 g) were used. The
      animals were randomized into groups of six animals. We performed tibialis muscle
      elongation using a previously described protocol. The animals were anesthetized
      and submitted to passive stretching of the anterior tibial muscle attached to a
      weight corresponding to 150% of the body mass of the animal for 20 min, rested
      for 3 min, and received a second traction for 20 min. The cytokines, tumor
      necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, and IL-10,
      edema, and C-reactive protein (CRP) levels were determined in the tibialis
      anterior muscle. RESULTS: Plasma extravasation of groups treated with different
      doses of laser energy, lesion +1 J (2.61 +/- 0.46), lesion +3 J (2.33 +/- 0.13),
      lesion +6 J (2.92 +/- 0.91), and lesion +9 J (2.80 +/- 0.55), shows a significant
      reduction of extravasation when compared with the injury group (5.46 +/- 1.09).
      Laser therapy was able to significantly reduce CRP and cytokine levels (TNF
      alpha, IL-1beta, IL-6, and IL-10). CONCLUSIONS: Laser photobiomodulation reduced
      skeletal muscle edema as well as cytokines and CRP, leading to a significant
      reduction in inflammatory markers.

PMID- 30096270
TI  - De-Escalation of Bone-Modifying Agents in Patients With Bone Metastases: The Best
      of Times and the Worst of Times?

PMID- 30096271
TI  - Integrative Therapies During and After Breast Cancer Treatment: ASCO Endorsement
      of the SIO Clinical Practice Guideline Summary.

PMID- 30096272
TI  - Progress in the Evaluation and Treatment of Small Bowel Neuroendocrine Tumors.

PMID- 30096274
TI  - Bone-Modifying Agents: Complicated to Use.

PMID- 30096275
TI  - Small Bowel Neuroendocrine Tumors: Big Advances in the Land of Small Tumors.

PMID- 30096273
TI  - Management of Small Bowel Neuroendocrine Tumors.
AB  - Small bowel neuroendocrine tumors (NETs) are increasing in incidence and are now
      the most common primary malignancies of the small intestine. Despite this
      increase, the vague presentation and slow growth of these tumors lead to long
      delays in diagnosis, and many patients present with metastases. Patients with
      metastatic small bowel NETs have a favorable disease prognosis, particularly when
      contrasted with other GI malignancies, and benefit from aggressive, multimodal
      therapy. During the past decade, the options for the diagnosis and treatment of
      small bowel NETs have increased considerably. This review provides a practical
      framework for the physician who seek to understand the epidemiology,
      presentation, diagnosis, and management of small bowel NETs.

PMID- 30096276
TI  - Oncology Patient Portal Enrollment at a Comprehensive Cancer Center: A Quality
      Improvement Initiative.
AB  - PURPOSE: Patient portals (PPs) provide patients access to their electronic health
      record and may facilitate active engagement in their care. Because PP use has not
      been well studied among patients with cancer, we sought to: understand the
      willingness of patients with cancer to use the PP, identify barriers to PP use,
      and improve PP accessibility. MATERIALS AND METHODS: As part of an institutional
      quality improvement initiative, we used a stakeholder-driven approach to examine
      PP use at the Dana-Farber Cancer Institute (Boston, MA). We conducted a survey
      across all ambulatory oncology practices as well as staff and patient focus
      groups in one ambulatory practice. We deployed three interventions to address
      barriers: staff education, staff-assisted enrollment support, and independent
      enrollment support. RESULTS: In October 2015, 1,019 (87%) of 1,178 eligible
      patients completed the survey (PP enrolled, 57%; non-PP enrolled, 43%). PP
      enrolled patients reported reviewing test results and appointment schedules. Non
      PP-enrolled patients cited difficult PP enrollment, lack of computer access, and
      concern about sharing data electronically as barriers to PP enrollment. Focus
      groups (staff, n = 20; patient representatives, n = 5) also identified lack of
      awareness of PP benefits as a barrier. The interventions, deployed from November
      to December 2015, increased PP enrollment from 47% to 53% by January 2016.
      CONCLUSION: Patients with cancer want to communicate with their team through the
      PP, but barriers to enrollment impede use. Straightforward system-level
      interventions may increase enrollment. Further work is necessary to ascertain the
      degree to which increased PP enrollment leads to greater engagement and better
      outcomes.

PMID- 30096278
TI  - Prior Authorization: This Will Take Time.

PMID- 30096277
TI  - Use of Bone-Modifying Agents in Myeloma and Bone Metastases: How Recent Dosing
      Interval Studies Have Affected Our Practice.
AB  - The management of bone lesions from advanced solid tumors and multiple myeloma
      typically includes use of a bone-modifying agent to reduce the risk of skeletal
      related events. Recent data demonstrate that when using zoledronic acid to reduce
      the risk of skeletal-related events in metastatic breast cancer, metastatic
      prostate cancer, and multiple myeloma, the dosing interval of zoledronic acid may
      be extended from every 4 weeks to every 12 weeks. The ASCO guidelines on the role
      of bone-modifying agents in metastatic breast cancer and multiple myeloma address
      zoledronic acid dosing intervals. Herein, we discuss how new data on dosing of
      bone-modifying agents influence our clinical practice.

PMID- 30096279
TI  - Editorial Comment.

PMID- 30096280
TI  - Isothermal calorimetry of a monoclonal antibody using a conventional differential
      scanning calorimeter.
AB  - It has been shown that isothermal calorimetry is able to provide critical
      information regarding the kinetics of denaturation/aggregation of monoclonal
      antibodies at temperatures below Tm. Those measurements, however, required
      sophisticated specialized instrumentation. Here, we demonstrate that similar
      measurements can be performed using widely available conventional differential
      scanning calorimeters (DSC) when operated in isothermal scan mode. The
      denaturation/aggregation kinetics of the anti-HIV monoclonal antibody VRC07-523LS
      was measured by isothermal DSC at ten degrees below Tm. It is shown that a
      readily available instrument provides similar kinetic information and can become
      an important tool for determining the long term stability of biologics.

PMID- 30096281
TI  - Effect of Timing of the First Bath on a Healthy Newborn's Temperature.
AB  - OBJECTIVE: To determine if a healthy newborn's age in hours (3, 6, or 9 hours
      after birth) affects thermoregulatory status after the first bath as indicated by
      axillary and skin temperatures. DESIGN: Quasi-experimental, mixed-model (between
      subjects and within subjects) design with hours of age as the nonrepeated
      variable and prebath and postbath temperatures as the repeated variables.
      SETTING: Family-centered care unit at an urban hospital in the southwestern
      United States. PARTICIPANTS: Healthy newborns (N = 75) 37 weeks or more completed
      gestation. METHODS: Mothers chose time of first bath based on available time
      slots (n = 25 newborns in each age group). Research nurses sponge bathed the
      newborns in the mothers' rooms. Axillary temperature, an index of core
      temperature, was measured with a digital thermometer, and skin temperature, an
      index of body surface temperature, was measured with a thermography camera.
      Temperatures were taken before the bath; immediately after the bath; and 5, 30,
      60, and 120 minutes after the bath. Immediately after the bath, newborns were
      placed in skin-to-skin care (SSC) for 60 or more minutes. RESULTS: We found a
      difference (p = .0372) in axillary temperatures between the 3- and 9-hour age
      groups, although this difference was not clinically significant (0.18  degrees F
      [0.10  degrees C]). We found no statistically significant differences in skin
      temperatures among the three age groups. Regardless of age group, axillary and
      skin temperatures initially decreased and then recovered after the bath.
      CONCLUSION: For up to 2 hours postbath, axillary and skin temperatures were not
      different between healthy newborns bathed at 3, 6, or 9 hours of age.
      Thermography holds promise for learning about thermoregulation, bathing, and SSC.

PMID- 30096283
TI  - Collection, isolation, in vitro culture, and laboratory transmission of
      Hirsutella eleutheratorum (Hypocreales: Ophiocordycipitaceae) from coffee berry
      borer on Hawai'i Island.
AB  - The insect pathogenic fungus Hirsutella eleutheratorum was first reported as a
      pathogen of coffee berry borer (CBB) Hypothenemus hampei in Colombia in 1993. A
      similar CBB pathogen identified as Hirsutella sp. was reported also from Colombia
      in 2007; attempts at isolation and in vitro culture of this fungus were
      unsuccessful. During 2016 and 2017 on the island of Hawai'i, extensive sampling
      of CBB populations was conducted in coffee fields treated with Beauveria bassiana
      based biopesticides and in untreated fields. Among the samples collected from two
      high-elevation sites in the district of South Kona were rare findings of adult
      foundress CBB infected with a species of Hirsutella fitting the description of H.
      eleutheratorum. Prevalence of the pathogen was, in all cases, very low (<1%),
      having no significant impact on pest populations, even under conditions
      supporting epizootics of B. bassiana. The fungus was readily isolated from
      freshly-killed CBB and cultured on potato dextrose agar (PDA). Molecular
      characterization identified the fungus as a member of the Hirsutella citriformis
      clade, which includes species recently placed in the genus Ophiocordyceps. Adult
      CBB exposed to fungus-killed beetles or to PDA cultures of the fungus succumbed
      to infection within 10-14 days. Under high-humidity laboratory conditions, the
      fungus emerged from the killed host and produced long, conidia-bearing synnemata
      characteristic of the species. To our knowledge, this is the first record of H.
      eleutheratorum from CBB in Hawai'i and the first account of isolation, in vitro
      culture, genetic characterization, host-to-host transfer, and culture-to-host
      transfer of this fungal pathogen.

PMID- 30096284
TI  - Activation of ERalpha and/or ERbeta ameliorates cognitive impairment and
      apoptosis in streptozotocin-induced diabetic mice.
AB  - Estrogen receptors (ERs) are thought to be associated with the onset and
      progression of neurodegenerative injuries and diseases, but the relationship and
      mechanisms underlying between ERs and cognition in type 1 diabetes remain
      elusive. In the current study, we investigated the effects of ERalpha and ERbeta
      on the memory impairment and apoptosis in streptozotocin-induced diabetic mice.
      We found that ERalpha and/or ERbeta activation using their agonists (0.5 mg/kg
      E2, PPT or DPN) ameliorate memory impairment in the Morris water maze (MWM) and Y
      maze tests and suppress apoptosis as evidenced by decreased caspase-3 activity
      and increased ratio of Bcl-2/Bax. Importantly, treatment with the pharmacologic
      ERs agonists caused significant increases in the membrane ERalpha and ERbeta
      expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus
      of diabetic mice. Our data indicate that ERalpha and ERbeta are involved in the
      cognitive impairment of type 1 diabetes and that activation of ERs via
      administration of ERs agonists could be a novel and promising strategy for the
      treatment of diabetic cognitive impairment.

PMID- 30096285
TI  - Epizootological study on Toxoplasma gondii in zoo animals in the Czech Republic.
AB  - Toxoplasma gondii is protozoan parasite with ability of causing disease in wide
      spectrum of animals; many species of animals in captivity died of clinical
      toxoplasmosis. The monitoring of T. gondii antibodies in zoo animals can be an
      important indicator of T. gondii circulation in zoo. The aim of this study was to
      examine sera of animals from eight Czech zoos by latex agglutination test with
      statistical evaluation and detect T. gondii DNA in stray cats and rodents
      captured in the zoos. T. gondii antibodies were detected in 33% of 1043 zoo
      animals without statistical difference between birds (27%, n = 74) and mammals
      (33%, n = 969). In birds, the chance to be infected with T. gondii was higher in
      Accipitriformes (71%) compared to Pelecaniformes (6%) (p < 0.0001). In mammals,
      the chance to be infected with T. gondii was higher in Carnivora (63%) compared
      to Cetarodactyla (30%), Perissodactyla (26%), Primates (28%) and Rodentia (13%)
      (p < 0.0001) and higher in Felidae (70%) compared to Bovidae (28%) and Equidae
      (28%) (p < 0.0001). Mammals with carnivore/scavenger way of feeding were in a
      higher risk of T. gondii infection compared to herbivores and omnivores (p <
      0.0001). T. gondii DNA was detected in tissue of one stray cat while in none of
      77 rodents caught in zoo. This study is the first report on toxoplasmosis in zoos
      from the Czech Republic including seroepidemiology and molecular detection.

PMID- 30096282
TI  - Katanin-like protein Katnal2 is required for ciliogenesis and brain development
      in Xenopus embryos.
AB  - Microtubule remodeling is critical for cellular and developmental processes
      underlying morphogenetic changes and for the formation of many subcellular
      structures. Katanins are conserved microtubule severing enzymes that are
      essential for spindle assembly, ciliogenesis, cell division, and cellular
      motility. We have recently shown that a related protein, Katanin-like 2
      (KATNAL2), is similarly required for cytokinesis, cell cycle progression, and
      ciliogenesis in cultured mouse cells. However, its developmental expression
      pattern, localization, and in vivo role during organogenesis have yet to be
      characterized. Here, we used Xenopus embryos to reveal that Katnal2 (1) is
      expressed broadly in ciliated and neurogenic tissues throughout embryonic
      development; (2) is localized to basal bodies, ciliary axonemes, centrioles, and
      mitotic spindles; and (3) is required for ciliogenesis and brain development.
      Since human KATNAL2 is a risk gene for autism spectrum disorders, our functional
      data suggest that Xenopus may be a relevant system for understanding the
      relationship of mutations in this gene to autism and the underlying molecular
      mechanisms of pathogenesis.

PMID- 30096286
TI  - The prevalence and distribution of Burkholderia pseudomallei in rice paddy within
      Hainan, China.
AB  - Melioidosis is an infectious disease caused by Burkholderia pseudomallei, mainly
      found in Southeast Asia and northern Australia. In Hainan, sporadic cases were
      first described in 1990; since then, more cases have been identified. No
      systematic study has yet been done to detect the environmental source of the
      organism and its true extent in Hainan. This study is aimed to confirm the
      prevalence of B. pseudomallei in soil samples in Hainan. 1080 soil samples from
      18 different counties were collected from 3 sampling points of 360 sites. They
      were screened for the presence of B. pseudomallei by Ashdown selective media.
      Suspected colonies of B. pseudomallei were confirmed by biochemical test and a
      specific PCR assay. 48 of 360 sites (13.3%) were positive for B. pseudomallei,
      including all coastal counties in Hainan Island. This study revealed the
      prevalence and distribution of B. pseudomallei in the soil environment in Hainan
      Island of southern China and may be helpful to understand the distribution of B.
      pseudomallei and to access its epidemiological importance.

PMID- 30096287
TI  - Exploring parasite heterogeneity using single-cell RNA-seq reveals a gene
      signature among sexual stage Plasmodium falciparum parasites.
AB  - The malaria parasite has a complex lifecycle, including several events of
      differentiation and stage progression, while actively evading immunity in both
      its mosquito and human hosts. Important parasite gene expression and regulation
      during these events remain hidden in rare populations of cells. Here, we combine
      a capillary-based platform for cell isolation with single-cell RNA-sequencing to
      transcriptionally profile 165 single infected red blood cells (iRBCs) during the
      intra-erythrocytic developmental cycle (IDC). Unbiased analyses of single-cell
      data grouped the cells into eight transcriptional states during IDC.
      Interestingly, we uncovered a gene signature from the single iRBC analyses that
      can successfully discriminate between developing asexual and sexual stage
      parasites at cellular resolution, and we verify five, previously undefined,
      gametocyte stage specific genes. Moreover, we show the capacity of detecting
      expressed genes from the variable gene families in single parasites, despite the
      sparse nature of data. In total, the single parasite transcriptomics holds
      promise for molecular dissection of rare parasite phenotypes throughout the
      malaria lifecycle.

PMID- 30096288
TI  - Genetic deletion of CB1 cannabinoid receptors exacerbates the Alzheimer-like
      symptoms in a transgenic animal model.
AB  - Activating CB1 cannabinoid receptor has been demonstrated to produce certain
      therapeutic effects in animal models of Alzheimer's disease (AD). In this study,
      we evaluated the specific contribution of CB1 receptor to the progression of AD
      like pathology in double transgenic APP/PS1 mice. A new mouse strain was
      generated by crossing APP/PS1 transgenic mice with CB1 knockout mice. Genetic
      deletion of CB1 drastically reduced the survival of APP/PS1 mice. In spite that
      CB1 mutant mice bearing the APP/PS1 transgene developed normally, they suddenly
      died within the first two months of life likely due to spontaneous seizures. This
      increased mortality could be related to an imbalance in the excitatory/inhibitory
      transmission in the hippocampus as suggested by the reduced density of inhibitory
      parvalbumin positive neurons observed in APP/PS1 mice lacking CB1 receptor at 7
      weeks of age. We also evaluated the AD-like phenotype of APP/PS1 mice
      heterozygous for the CB1 deletion at 3 and 6 months of age. The memory impairment
      associated to APP/PS1 transgene was accelerated in these mice. Neither the
      soluble levels of Abeta or the density of Abeta plaques were modified in APP/PS1
      mice heterozygous for CB1 deletion at any age. However, the reduction in CB1
      receptor expression decreased the levels of PSD-95 protein in APP/PS1 mice,
      suggesting a synaptic dysfunction in these animals that could account for the
      acceleration of the memory impairment observed. In summary, our results suggest a
      crucial role for CB1 receptor in the progression of AD-related pathological
      events.

PMID- 30096289
TI  - Intranuclear delivery of synthetic nuclear factor-kappa B p65 reduces
      inflammasomes after surgery.
AB  - Patients undergoing surgery can suffer from various complications, including post
      operative bleeding, local or systematic infection, and neurologic disorders.
      Major surgery can initiate innate immune responses and trigger overproduction of
      inflammatory mediators, which can contribute to organ dysfunction. Inflammasomes
      are innate immune complexes, which are connected to the pathogenesis of various
      diseases, including atherosclerosis, hemorrhagic brain injury, and Alzheimer's
      disease. In the present study, we hypothesized that nucleotide-binding
      oligomerization domain-containing-like receptor protein (NLRP) inflammasomes may
      have a role in the pathological effects of surgery. Therefore, we designed a
      protein inhibitor of nuclear factor kappa B (NF-kappaB) p65 transcripts, called
      nt-p65-TMD (nuclear transducible (nt) transcription modulated domain (TMD) of
      RelA (p65)), that can penetrate the nucleus, and evaluated its therapeutic
      efficacy for dampening surgery-induced inflammasome activation. It was found that
      the nt-p65-TMD significantly reduced the NLRP1 inflammasome complex components
      (NLRP1, ASC, and Caspase-1) and interleukin (IL)-1beta and IL-18 productions in
      the spleen after surgery. In the spleen, specific cell population and selective
      mediators were altered after surgery with/without nt-p65-TMD treatment. Also, we
      found that treatment of nt-p65-TMD decreased cell death in the spleen after
      surgery. Therefore, nt-p65-TMD is a potential novel strategy for reducing surgery
      induced NLRP1 inflammasome and complications.

PMID- 30096290
TI  - Controversies in family planning: persistently elevated serum human chorionic
      gonadotropin levels after aspiration abortion.
AB  - Low but rising serum human chorionic gonadotropin (hCG) levels occur infrequently
      after an induced abortion. Because this scenario rarely occurs after suction
      aspiration, clinicians may have higher suspicion for an uncommon diagnosis. The
      differential diagnosis includes both common and uncommon diagnoses, such as
      incomplete abortion, heterotopic or ectopic pregnancy, a new intrauterine
      pregnancy and gestational trophoblastic neoplasia. The etiology of this
      presentation may be unclear, especially in the absence of abnormal bleeding or
      pain which would suggest incomplete abortion, or when significant time has passed
      since the procedure. We describe two cases of an uncommon presentation of
      retained products of conception after aspiration abortion in which hCG levels
      were low but rising.

PMID- 30096292
TI  - Predictors of Pathologic Tumor Invasion and Prognosis for Ground Glass Opacity
      Featured Lung Adenocarcinoma.
AB  - BACKGROUND: We make surgical strategies for ground glass opacity (GGO) nodules
      currently based on thin-section (TS) computed tomography (CT) findings. Whether
      radiologic measurements could precisely predict tumor invasion and prognosis of
      GGO-featured lung adenocarcinoma is uncertain. METHODS: We retrospectively
      evaluated medical records of patients with radiologic GGO nodules undergoing a
      surgical procedure at Fudan University Shanghai Cancer Center. The study
      endpoints were the predictive value and prognostic significance of radiologic
      measurements (consolidation-to-tumor ratio value, consolidation size, and tumor
      size) for pathologic lung adenocarcinoma. RESULTS: In this study 736 patients and
      841 GGO nodules were included. Five-year lung cancer-specific regression-free
      survival (LCS-RFS) rate was 95.76% (95% confidence interval [CI], 93.01% to
      97.44%). The 5-year LCS overall survival (OS) rate was 98.99% (95% CI, 97.69% to
      99.57%). Multivariable analysis showed that tumor invasion (invasive
      adenocarcinoma [IAD] vs adenocarcinoma in situ [AIS]/minimally invasive
      adenocarcinoma [MIA], p = 0.020) was the only independent predictor for 5-year
      LCS-RFS. IAD (hazard ratio, 15.98; 95% CI, 1.55 to 164.35) was correlated with a
      higher risk of recurrence. Kaplan-Meier analysis showed that only tumor invasion
      status (IAD vs AIS/MIA, p = 0.003) could predict 5-year lung cancer-specific
      overall survival (LCS-OS), and IAD had a worse LCS-OS than AIS and MIA. A part
      solid component (odds ratio [OR], 9.09; 95% CI, 2.71 to 30.47; p = 0.000), large
      consolidation size (OR, 3.11; 95% CI, 1.03 to 9.40; p = 0.045), and large tumor
      size (OR, 5.48; 95% CI, 2.68 to 11.19; p = 0.000) were associated with pathologic
      IAD. For IAD <= 20 mm, segmentectomy and lobectomy had better 5-year LCS-RFS than
      wedge resection, although the difference was statistically insignificant (p =
      0.367). The three types of surgeries provided the similar 5-year LCS-OS (p =
      0.834). CONCLUSIONS: Radiologic measurements could not precisely predict tumor
      invasion and prognosis. Making treatment strategies solely according to TS-CT
      findings for GGO tumor is inappropriate.

PMID- 30096291
TI  - Distinguishing neurocysticercosis epilepsy from epilepsy of unknown etiology
      using a minimal serum mass profiling platform.
AB  - Neurocysticercosis is associated with epilepsy in pig-raising communities with
      poor sanitation. Current internationally recognized diagnostic guidelines for
      neurocysticercosis rely on brain imaging, a technology that is frequently not
      available or not accessible in areas endemic for neurocysticercosis. Minimally
      invasive and low-cost aids for diagnosing neurocysticercosis epilepsy could
      improve treatment of neurocysticercosis. The goal of this study was to test the
      extent to which patients with neurocysticercosis epilepsy, epilepsy of unknown
      etiology, idiopathic headaches and among different types of neurocysticercosis
      lesions could be distinguished from each other based on serum mass profiling. For
      this, we collected sera from patients with neurocysticercosis-associated
      epilepsy, epilepsy of unknown etiology, recovered neurocysticercosis, and
      idiopathic headaches then performed binary group comparisons among them using
      electrospray ionization mass spectrometry. A leave one [serum sample] out cross
      validation procedure was employed to analyze spectral data. Sera from
      neurocysticercosis patients was distinguished from epilepsy of unknown etiology
      patients with a p-value of 10-28. This distinction was lost when samples were
      randomized to either group (p-value = 0.22). Similarly, binary comparisons of
      patients with neurocysticercosis who has different types of lesions showed that
      different forms of this disease were also distinguishable from one another. These
      results suggest neurocysticercosis epilepsy can be distinguished from epilepsy of
      unknown etiology based on biomolecular differences in sera detected by mass
      profiling.

PMID- 30096293
TI  - Alpha-lipoic acid, but not di-hydrolipoic acid, activates Nrf2 response in
      primary human umbilical-vein endothelial cells and protects against TNF-alpha
      induced endothelium dysfunction.
AB  - The antioxidants role in cell response regulation attracted great interest in the
      last decades and it is undergoing to a profound reconsideration. The mere concept
      of "biological antioxidant" has been frequently misconceived or misused, possibly
      leading to the misinterpretation of some experimental observation. Organosulfur
      compounds in general and alpha-lipoic acid, a dithiol molecule, can be considered
      a typical example of the kind. Reduced alpha-lipoic acid, dehydrolipoic acid has
      been in fact originally considered a bona fide, reducing, electron donor
      molecule. A more recent approach, according to stoichiometric and thermodynamic
      evidences, lead to a reinterpretation of the biochemical role of "antioxidants".
      The electrophilic nature of oxidized nucleophilic molecules, including alpha
      lipoic acid, renders more plausible a mechanism based on the ability to activate
      Nrf2/EpRE mediated hormetic response. In this study, we demonstrate that nmolar
      concentrations of oxidized alpha-lipoic acid, but not dehydrolipoic acid, protect
      human umbilical primary endothelial cells (HUVEC) from TNF-alpha induced
      dysfunction, inhibit NF-kappaB activation and block apoptosis following the
      activation of Nrf2 transcription factor. Our observations corroborate the concept
      that the major, if not the unique, mechanism by which alpha-lipoic acid can non
      enzymatically exert its reducing activity is related to the electrophilic nature
      of the oxidized form.

PMID- 30096294
TI  - PIM2 survival kinase is upregulated in a p53-dependent manner in cells treated
      with camptothecin or co-treated with actinomycin D and nutlin-3a.
AB  - The p53 protein is an inducer of apoptosis, acting as a transcriptional regulator
      of apoptotic genes. In a previous study, we found that actinomycin D and nutlin
      3a (A + N) synergistically activate p53. To better understand the molecular
      consequences of this synergism, we incubated arrays of antibodies against
      apoptotic proteins with extracts of A549 cells in which p53 had been activated.
      We found that strong activation of p53, marked by serine 46 and 392
      phosphorylation, was associated with inactivating phosphorylation of proapoptotic
      BAD protein on serine 136. Investigation of the source of this phosphorylation
      revealed that activation of p53 was associated with accumulation of PIM2, a
      survival kinase. The accumulation of PIM2 following treatment with A + N was
      suppressed in p53-knockdown cells. Others discovered that PIM2 was activated by
      cooperatively acting p53 molecules. Our results are consistent with this finding.
      Moreover, we found that in A549 cells, the treatment with A + N stimulated in p53
      dependent fashion the expression of other high cooperativity p53 target genes,
      DRAXIN and H19. Activation of antiapoptotic H19 can mechanistically explain
      relatively low rate of apoptosis of A549 cells exposed to A + N. We conclude that
      PIM2, DRAXIN and H19 are efficiently stimulated by strongly activated p53
      molecules, probably acting cooperatively.

PMID- 30096295
TI  - Paeoniflorin regulates GALNT2-ANGPTL3-LPL pathway to attenuate dyslipidemia in
      mice.
AB  - N-acetylgalactosaminyltransferase 2-Angiopoietin-like protein 3-lipoprotein
      lipase (GALNT2-ANGPTL3-LPL) pathway may be a useful pharmacologic objective for
      dyslipidemia. The present study was conducted to test the effect of paeoniflorin,
      a monoterpene Glycoside, on dyslipidemia in mice. Fifty mice were randomly
      divided into five groups (n = 10): three groups of apolipoprotein E-null (ApoE-/
      ) mice treated with paeoniflorin (10 or 20 or 30 mg/kg/day), untreated ApoE-/-
      mice group, and C57BL/6J control group. Six weeks after treatment, expression of
      hepatic ANGPTL3, hepatic GALNT2 and adipose tissue LPL, lipid levels in the liver
      and blood were quantified. Treatment with paeoniflorin (10 or 20 or 30 mg/kg)
      obviously down-regulated expression of ANGPTL3 and up-regulated expressions of
      GALNT2 and LPL concomitantly with elevated plasma high-density lipoprotein
      cholesterol level, reduced plasma concentrations of low-density lipoprotein
      cholesterol, total cholesterol, triglyceride, malonaldehyde, and 8-isoprostane.
      The present results suggest that paeoniflorin regulates GALNT2-ANGPTL3-LPL
      pathway to attenuate dyslipidemia in mice.

PMID- 30096296
TI  - 20(S)-25-methoxyl-dammarane-3beta,12beta,20-triol attenuates endoplasmic
      reticulum stress via ERK/MAPK signaling pathway.
AB  - Endoplasmic reticulum (ER) stress, together with unfolded protein response (UPR),
      can remove unfolded proteins and promote survival. However, severe and prolonged
      ER stress leads to cell death, tissue injury, and many serious diseases.
      Therefore, it is essential to identify drugs that can attenuate ER stress for ER
      related disease treatment. A great deal of research shows that selenoprotein S
      (SelS) is a sensitive and ideal marker of ER stress. Here, we used a firefly
      luciferase reporter driven by SelS gene promoter to screen natural compounds that
      can attenuate ER stress. Then we identified compound 20(S)-25-methoxyl-dammarane
      3beta,12beta,20-triol (25-OCH3-PPD) could inhibit the promoter activity of SelS,
      further results showed that 25-OCH3-PPD effectively inhibited tunicamycin (TM)
      induced up-regulation of SelS expression in both mRNA and protein levels.
      Moreover, 25-OCH3-PPD significantly inhibited glucose-regulated protein 78
      (GRP78; the major ER stress marker) expression in TM-induced ER stress in HepG2
      and HEK293T cells, suggesting that 25-OCH3-PPD could attenuate ER stress in these
      cells. Mechanism studies showed that 25-OCH3-PPD significantly activated ERK/MAPK
      signaling pathway, and the inhibition of ERK/MAPK by U0126 dramatically abolished
      the inhibitory effect of 25-OCH3-PPD on ER stress, suggesting that 25-OCH3-PPD
      attenuated ER stress at least partially through activation of ERK/MAPK signaling
      pathway. Taken together, our studies indicate that 25-OCH3-PPD is a novel small
      molecular compound reducing ER stress, and a potential drug for treating diseases
      associated with ER stress.

PMID- 30096297
TI  - A novel highly potent and selective 11beta-hydroxysteroid dehydrogenase type 1
      inhibitor, INU-101.
AB  - 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is a cortisol
      regenerating enzyme that amplifies tissue glucocorticoid levels, especially in
      the liver and adipose tissue. Knockout mice or a selective inhibitor of 11beta
      HSD1 improves metabolic syndrome parameters in preclinical models and human
      clinical trials. Here, we evaluated the therapeutic potential of INU-101, a
      potent and selective oral inhibitor of 11beta-HSD1. The in vitro activity of
      11beta-HSD1 was measured using the homogeneous time-resolved fluorescence (HTRF)
      assay. Differentiated adipocytes were used to evaluate the cellular 11beta-HSD1
      activity. To determine the inhibitory effects on 11beta-HSD1 in tissues, we
      performed ex vivo studies using liver and adipose tissue isolated from C57BL/6 J
      mice and Cynomolgus monkeys. KKAy mice, ob/ob mice and ZDF rats were administered
      INU-101 to evaluate whether this compound ameliorated metabolic abnormalities in
      obese and diabetic animals. INU-101 had highly potent inhibitory activity in
      mouse, monkey and human 11beta-HSD1, derived from liver microsomes. The oral
      administration of INU-101 significantly inhibited 11beta-HSD1 activity in the
      liver and adipose tissue of mice and monkeys. In KKAy mice, ob/ob mice and ZDF
      rats, the oral administration of INU-101 enhanced insulin sensitivity and lowered
      the fasting blood glucose level. Furthermore, INU-101 treatment decreased the
      body weight and ameliorated an improved lipid profile in the diabetic mouse
      model. These results suggest that the 11beta-HSD1 inhibitor, INU-101 may serve as
      a novel drug candidate for the treatment of type 2 diabetes and metabolic
      syndrome.

PMID- 30096298
TI  - Pharmacological treatments for opiate and alcohol addiction: A historical
      perspective of the last 50 years.
AB  - Addiction pharmacotherapy aims to prevent drug abstinence symptoms, reduce drug
      craving and relapse, and normalize physiologic functions disrupted by chronic use
      of the drug. During the last 50 years, there has been an enormous revolution in
      pharmacotherapy for drug addiction. From abstinence as practically the only
      treatment option available, there are now multiple drugs on the market that have
      proved their efficacy in treating opiate and alcohol disorders. The present
      review will focus on the pharmacological treatments of the drugs whose
      consumption most affects individuals and society: alcohol and opiates. We will
      review the drugs most widely prescribed to prevent relapse and maintain
      abstinence, as well as those designed to reduce the consumption of short-acting
      drugs (e.g. maintenance therapies) since the 1960s. Methadone and buprenorphine
      are the most widely used maintenance therapies for opiate addicts, although new
      pharmacological depot systems of naltrexone are showing promising results. For
      alcohol use disorders, acamprosate, nalmefene and naltrexone are replacing
      disulfiram prescriptions, and a wide variety of new products are currently under
      study. The number of new pharmacological targets already on clinical trials and
      the advanced new ways to administer classic therapies can improve the success
      rate of the pharmacotherapy for opioid and alcohol addiction.

PMID- 30096299
TI  - Molecular Diversity and Specializations among the Cells of the Adult Mouse Brain.
AB  - The mammalian brain is composed of diverse, specialized cell populations. To
      systematically ascertain and learn from these cellular specializations, we used
      Drop-seq to profile RNA expression in 690,000 individual cells sampled from 9
      regions of the adult mouse brain. We identified 565 transcriptionally distinct
      groups of cells using computational approaches developed to distinguish
      biological from technical signals. Cross-region analysis of these 565 cell
      populations revealed features of brain organization, including a gene-expression
      module for synthesizing axonal and presynaptic components, patterns in the co
      deployment of voltage-gated ion channels, functional distinctions among the cells
      of the vasculature and specialization of glutamatergic neurons across cortical
      regions. Systematic neuronal classifications for two complex basal ganglia nuclei
      and the striatum revealed a rare population of spiny projection neurons. This
      adult mouse brain cell atlas, accessible through interactive online software
      (DropViz), serves as a reference for development, disease, and evolution.

PMID- 30096300
TI  - Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti
      PD-1 Immunotherapy.

PMID- 30096301
TI  - Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer.

PMID- 30096304
TI  - SnapShot: Unconventional miRNA Functions.
AB  - MicroRNAs (miRNAs) are synonymous with post-transcriptional repression of target
      genes. A number of studies, however, have reported miRNAs functioning outside
      this paradigm, and this SnapShot outlines these unconventional ways in which
      miRNAs can exert regulatory functions. To view this SnapShot, open or download
      the PDF.

PMID- 30096303
TI  - Dissociable Structural and Functional Hippocampal Outputs via Distinct Subiculum
      Cell Classes.

PMID- 30096305
TI  - Enhancing Therapy: It's about Time.
AB  - How diet and obesity impact diurnal changes in physiology remains unclear. In
      this issue of Cell, Guan et al. report that diet-induced obesity modulates the
      activity of circadian gene enhancers including those regulating lipid metabolism
      and show that the efficacy of lipid-lowering drugs depends on the time of
      administration.

PMID- 30096306
TI  - Viral Teamwork Pushes CRISPR to the Breaking Point.
AB  - Viruses have evolved inhibitors to counteract the CRISPR immune response, but
      they are not fully potent and need some time to be expressed after the beginning
      of infection. In this issue of Cell, Borges et al. and Landsberger et al. show
      that sequential infection gradually immunosuppresses the host to allow effective
      CRISPR inhibition.

PMID- 30096307
TI  - Single-Molecule Analysis of a Viral Fusion Protein Illuminates a Fusion-Active
      Intermediate State.
AB  - The influenza virus hemagglutinin (HA) fusion glycoprotein mediates viral entry
      into host cells through its receptor binding and membrane fusion activities. In
      this issue of Cell, Das et al. use single-molecule Forster resonance energy
      transfer (smFRET) to monitor HA conformational dynamics. Their study reveals this
      prototypical class I fusion protein to be a highly dynamic molecule capable of
      reversibly sampling multiple states, including on-pathway fusion intermediates
      between pre-fusion and post-fusion endpoints. These findings challenge long-held
      ideas for how HA functions and move the field closer to obtaining a mechanistic
      understanding of how class I fusion proteins mediate membrane fusion.

PMID- 30096308
TI  - Sequencing Diversity One Cell at a Time.
AB  - Single-cell RNA sequencing provides a new approach to an old problem: how to
      study cellular diversity in complex biological systems. Three studies-Saunders et
      al., Zeisel et al., and Davie et al.-deploy this technique on an unprecedented
      scale to reveal transcriptional patterns that distinguish cells in the nervous
      systems of mice and flies.

PMID- 30096309
TI  - Krebs Cycle Reimagined: The Emerging Roles of Succinate and Itaconate as Signal
      Transducers.
AB  - Krebs cycle intermediates traditionally link to oxidative phosphorylation whilst
      also making key cell components. It is now clear that some of these metabolites
      also act as signals. Succinate plays an important role in inflammatory, hypoxic,
      and metabolic signaling, while itaconate (from another Krebs cycle intermediate,
      cis-aconitate) has an anti-inflammatory role.

PMID- 30096310
TI  - Microbiome: Focus on Causation and Mechanism.
AB  - There is tremendous enthusiasm for the microbiome in academia and industry. This
      Perspective argues that in order to realize its potential, the field needs to
      focus on establishing causation and molecular mechanism with an emphasis on
      phenotypes that are large in magnitude, easy to measure, and unambiguously driven
      by the microbiota.

PMID- 30096311
TI  - Emerging Roles for Intermolecular RNA-RNA Interactions in RNP Assemblies.
AB  - Eukaryotic cells contain large assemblies of RNA and protein, referred to as
      ribonucleoprotein (RNP) granules, which include cytoplasmic P-bodies, stress
      granules, and neuronal and germinal granules, as well as nuclear paraspeckles,
      Cajal bodies, and RNA foci formed from repeat expansion RNAs. Recent evidence
      argues that intermolecular RNA-RNA interactions play a role in forming and
      determining the composition of certain RNP granules. We hypothesize that
      intermolecular RNA-RNA interactions are favored in cells yet are limited by RNA
      binding proteins, helicases, and ribosomes, thereby allowing normal RNA function.
      An over-abundance of intermolecular RNA-RNA interactions may be toxic since
      perturbations that increase RNA-RNA interactions such as long repeat expansion
      RNAs, arginine-containing dipeptide repeat polypeptides, and sequestration or
      loss of abundant RNA-binding proteins can contribute to degenerative diseases.

PMID- 30096312
TI  - Divergent Routes toward Wnt and R-spondin Niche Independency during Human Gastric
      Carcinogenesis.
AB  - Recent sequencing analyses have shed light on heterogeneous patterns of genomic
      aberrations in human gastric cancers (GCs). To explore how individual genetic
      events translate into cancer phenotypes, we established a biological library
      consisting of genetically engineered gastric organoids carrying various GC
      mutations and 37 patient-derived organoid lines, including rare genomically
      stable GCs. Phenotype analyses of GC organoids revealed divergent genetic and
      epigenetic routes to gain Wnt and R-spondin niche independency. An unbiased
      phenotype-based genetic screening identified a significant association between
      CDH1/TP53 compound mutations and the R-spondin independency that was functionally
      validated by CRISPR-based knockout. Xenografting of GC organoids further
      established the feasibility of Wnt-targeting therapy for Wnt-dependent GCs. Our
      results collectively demonstrate that multifaceted genetic abnormalities render
      human GCs independent of the stem cell niche and highlight the validity of the
      genotype-phenotype screening strategy in gaining deeper understanding of human
      cancers.

PMID- 30096315
TI  - Ectopic expression of factor VIII in MSCs and hepatocytes derived from rDNA
      targeted hESCs.
AB  - Hemophilia A is an X-linked recessive bleeding disorder caused by FVIII gene
      deficiency, which may result in spontaneous joint hemorrhages or life-threatening
      bleeding. Currently, cell-based gene therapy via ex vivo transduction of
      transplantable cells with integrating gene-expressing vectors offers an
      attractive treatment for HA. In present study, we targeted an expression cassette
      of B-domain-deleted FVIII into the ribosomal DNA (rDNA) locus of human embryonic
      stem cells (hESCs) by transfection with a nonviral targeting plasmid pHrn. The
      targeted hESCs clone could be expanded and retained the main pluripotent
      properties of differentiation into three germ layers both in vitro and in vivo.
      Importantly, under defined induction conditions, the targeted hESCs could
      differentiated into functional mesenchymal stem cells (MSCs) and hepatocytes, as
      validated by relevant specific cell markers and functional examination.
      Tumorgenesis assay demonstrated that these cells are relatively safe for future
      applications. Analysis on gene expression revealed that exogenous FVIII mRNA and
      FVIII proteins were both present in differentiated MSCs and hepatocytes. These
      results indicated that through gene targeting at hESCs rDNA locus a persistent
      cell source of transplantable genetic-modified cells can be accomplished for HA
      therapy.

PMID- 30096314
TI  - Molecular Architecture of the Mouse Nervous System.
AB  - The mammalian nervous system executes complex behaviors controlled by
      specialized, precisely positioned, and interacting cell types. Here, we used RNA
      sequencing of half a million single cells to create a detailed census of cell
      types in the mouse nervous system. We mapped cell types spatially and derived a
      hierarchical, data-driven taxonomy. Neurons were the most diverse and were
      grouped by developmental anatomical units and by the expression of
      neurotransmitters and neuropeptides. Neuronal diversity was driven by genes
      encoding cell identity, synaptic connectivity, neurotransmission, and membrane
      conductance. We discovered seven distinct, regionally restricted astrocyte types
      that obeyed developmental boundaries and correlated with the spatial distribution
      of key glutamate and glycine neurotransmitters. In contrast, oligodendrocytes
      showed a loss of regional identity followed by a secondary diversification. The
      resource presented here lays a solid foundation for understanding the molecular
      architecture of the mammalian nervous system and enables genetic manipulation of
      specific cell types.

PMID- 30096318
TI  - Component-resolved diagnosis in allergic disease: Utility and limitations.
AB  - Component resolved diagnosis (CRD) is a microarray-based diagnostic solution
      capable of simultaneously analysing specific IgE antibodies against 112
      allergenic components, providing sensitivity patterns for multi-sensitised or
      complex patients. The CRD is indicated for these patients, especially those with
      concomitant respiratory and food allergies. This study reivews the method, its
      utility, limitations, and our experience in allergic diseases with difficult
      etiologic diagnosis (eosinophilic esophagitis, occupational asthma and drug
      allergy).

PMID- 30096319
TI  - Actinomycosis-induced adnexal and uterine masses mimicking malignancy on FDG
      PET/CT.

PMID- 30096316
TI  - Classified status of smoking and quitting has different associations with
      dyslipidemia in residents in northeast China.
AB  - BACKGROUND: Various smoking status and high prevalence of dyslipidemia in
      residents exist in northeast China. However, associations of dyslipidemia with
      smoking status remain unclear. METHODS: A total of 17,114 participants selected
      by a multistage stratified cluster random sampling design were enrolled from a
      cross-sectional study conducted in northeast China. Associations of dyslipidemia
      with smoking/quitting status (smoking amount, smoking duration, and quitting
      duration) were investigated using multiple logistic regression. RESULTS:
      Prevalence (39.2%) of dyslipidemia existed in residents in northeast China.
      Smoking amount was associated with dyslipidemia (1-10 cigarettes daily: OR =
      1.19, 95% CI: 1.08-1.32; 11-20 cigarettes daily: OR = 1.29, 95% CI: 1.16-1.42;
      and over 20 cigarettes daily: OR = 1.51, 95% CI: 1.25-1.83). Smoking duration was
      associated with dyslipidemia risk (6-10 years: OR = 1.75, 95% CI: 1.51-2.03; 11
      15 years: OR = 1.85, 95% CI: 1.51-2.26; and >=15 years: OR = 1.12, 95% CI: 1.02
      1.23). Quitting duration (1-5 years) was associated with dyslipidemia (OR = 1.26,
      95% CI: 1.07-1.48); however, we found no statistically significant associations
      between dyslipidemia and quitting duration (over 6 years). CONCLUSIONS:
      Dyslipidemia risk is positively associated with smoking/quitting status. Smoking
      amount and smoking duration may co-determine dyslipidemia risk, and quitting
      duration (>6 years) is necessary for reducing dyslipidemia risk.

PMID- 30096317
TI  - Retrospective study on the outcomes of infantile tufted angioma complicated by
      Kasabach-Merritt Phenomenon.
AB  - OBJECTIVE: To analyze the clinical characteristics and treatment of pediatric
      tufted angiomas(TA)complicated by Kasabach-Merritt Phenomenon (KMP). METHOD: A
      retrospective analysis was conducted on the clinical data and follow-up data of
      13 patients diagnosed with TA complicated by KMP. Five male and 8 female patients
      with an average age of 5.7 months (range, 29 days to 1 year) were treated with
      surgery between January 2009 and June 2012. According to the size and location of
      lesions and the degree of thrombocytopenia, complete or subtotal resection was
      performed. The median follow-up period was 3.4 years (range, 1.7 years to 5.2
      years). Therapeutic outcomes were evaluated by platelet count and lesion size.
      RESULTS: Curative treatment of KMP is defined as restoration of normal hemostasis
      and elimination of tumor cells. Twelve patients achieved curative treatment and
      one died of multiple organ failure after operation. Ten patients received
      complete resection and three patients received incomplete resection. Thrombocyte
      count, hemoglobin and blood coagulation were respectively restored to normal
      levels within 1-3 days and 1-2 weeks post complete resection operation. One of
      the three patients who received subtotal resection operation died. In the other
      two patients, the platelet count fluctuated over time but remained above 60 * 109
      /L, a significantly higher level than the preoperational level. Residual lesions
      slowly disappeared after continuous medication 3-6 months post operation.
      CONCLUSION: Early surgical treatment of patients with TA complicated with KMP
      resulted in significantly higher curative rate and reduced side-effects of drugs.

PMID- 30096320
TI  - Vaginal antifungal during pregnancy and risk of spontaneous abortions.

PMID- 30096313
TI  - Systematic Analysis of Monoclonal Antibodies against Ebola Virus GP Defines
      Features that Contribute to Protection.
AB  - Antibodies are promising post-exposure therapies against emerging viruses, but
      which antibody features and in vitro assays best forecast protection are unclear.
      Our international consortium systematically evaluated antibodies against Ebola
      virus (EBOV) using multidisciplinary assays. For each antibody, we evaluated
      epitopes recognized on the viral surface glycoprotein (GP) and secreted
      glycoprotein (sGP), readouts of multiple neutralization assays, fraction of
      virions left un-neutralized, glycan structures, phagocytic and natural killer
      cell functions elicited, and in vivo protection in a mouse challenge model.
      Neutralization and induction of multiple immune effector functions (IEFs)
      correlated most strongly with protection. Neutralization predominantly occurred
      via epitopes maintained on endosomally cleaved GP, whereas maximal IEF mapped to
      epitopes farthest from the viral membrane. Unexpectedly, sGP cross-reactivity did
      not significantly influence in vivo protection. This comprehensive dataset
      provides a rubric to evaluate novel antibodies and vaccine responses and a
      roadmap for therapeutic development for EBOV and related viruses.

PMID- 30096322
TI  - Reply.

PMID- 30096323
TI  - Early and late preeclampsia are characterized by high cardiac output, but in the
      presence of fetal growth restriction, cardiac output is low: insights from a
      prospective study.

PMID- 30096321
TI  - Receipt of adjuvant endometrial cancer treatment according to race: an NRG
      Oncology/Gynecologic Oncology Group 210 Study.
AB  - BACKGROUND: Black women with endometrial cancer are more likely to die of their
      disease compared with white women with endometrial cancer. These survival
      disparities persist even when disproportionately worse tumor characteristics
      among black women are accounted. Receipt of less complete adjuvant treatment
      among black patients with endometrial cancer could contribute to this disparity.
      OBJECTIVE: We assessed the hypothesis that black women with endometrial cancer
      are less likely than their white counterparts to receive adjuvant treatment
      within subgroups defined by tumor characteristics in the NRG Oncology/Gynecology
      Oncology Group 210 Study. STUDY DESIGN: Our analysis included 615 black and 4283
      white women with endometrial cancer who underwent hysterectomy. Women completed a
      questionnaire that assessed race and endometrial cancer risk factors. Tumor
      characteristics were available from pathology reports and central review. We
      categorized women as low-, intermediate-, or high-risk based on the European
      Society for Medical Oncology definition. Adjuvant treatment was documented during
      postoperative visits and was categorized as no adjuvant treatment (54.3%),
      radiotherapy only (16.5%), chemotherapy only (15.2%), and radiotherapy plus
      chemotherapy (14.0%). We used polytomous logistic regression to estimate odds
      ratios and 95% confidence intervals for multivariable-adjusted associations
      between race and adjuvant treatment in the overall study population and
      stratified by tumor subtype, stage, or European Society for Medical Oncology risk
      category. RESULTS: Overall, black women were more likely to have received
      chemotherapy only (odds ratio, 1.40; 95% confidence interval, 1.04-1.86) or
      radiotherapy plus chemotherapy (odds ratio, 2.01; 95% confidence interval, 1.54
      2.62) compared with white women in multivariable-adjusted models. No racial
      difference in the receipt of radiotherapy only was observed. In tumor subtype
      stratified models, black women had higher odds of receiving radiotherapy plus
      chemotherapy than white women when diagnosed with low-grade endometrioid (odds
      ratio, 2.04; 95% confidence interval, 1.06-3.93) or serous tumors (odds ratio,
      1.81; 95% confidence interval, 1.07-3.08). Race was not associated with adjuvant
      treatment among women who had been diagnosed with other tumor subtypes. In stage
      stratified models, we observed no racial differences in the receipt of adjuvant
      treatment. In models that were stratified by European Society for Medical
      Oncology risk group, black women with high-risk cancer were more likely to
      receive radiotherapy plus chemotherapy compared with white women (odds ratio,
      1.41; 95% confidence interval, 1.03-1.94). CONCLUSION: Contrary to our
      hypothesis, we observed higher odds of specific adjuvant treatment regimens among
      black women as compared with white women within specific subgroups of endometrial
      cancer characteristics.

PMID- 30096324
TI  - Patching retinal breaks with polyethylene glycol-based synthetic hydrogel sealant
      for retinal detachment in rabbits.
AB  - The purpose of this study was to evaluate absorbable polyethylene glycol (PEG)
      based synthetic hydrogel as a sealant for retinal breaks in rhegmatogenous
      retinal detachment (RD). A three-port, 25-gauge vitrectomy was performed on nine
      Dutch pigmented rabbit eyes. Subsequently, RD was induced by creating a retinal
      break. The retina was then reattached by fluid-air exchange. In six of nine eyes
      (RD-PEG group), PEG sealant was applied to completely cover the retinal breaks,
      and then photopolymerized with light; thereafter, intravitreous air was replaced
      with balanced salt solution (BSS). In the remaining three eyes (RD group), PEG
      sealant was not applied, but the intravitreous air was replaced with BSS.
      Ophthalmological examinations and intraocular pressure measurements were
      conducted preoperatively, and at 1 and 7 days, and 1, 3, and 6 months
      postoperatively. Histological examinations of the eyes were performed after 6
      postoperative months. At surgery, retinal reattachment with PEG sealant was
      achieved in all eyes in the RD-PEG group. Fundoscopic and optical coherence
      tomographic examinations revealed that the retina remained attached in all the
      eyes of the RD-PEG group throughout the 6-month observation period. Histological
      examination revealed no signs of damage in the retinal layers at the edges of the
      retinal breaks that were in contact with the sealant. In the RD group, the
      retinas detached in all eyes within 7 days postoperatively. The PEG sealant
      closed the retinal breaks and maintained retinal reattachment. Intraocular
      tamponade was not necessary.

PMID- 30096326
TI  - A cell culture condition that induces the mesenchymal-epithelial transition of
      dedifferentiated porcine retinal pigment epithelial cells.
AB  - The pathological change of retinal pigment epithelial (RPE) cells is one of the
      main reasons for the development of age-related macular degeneration (AMD). Thus,
      cultured RPE cells are a proper cell model for studying the etiology of AMD in
      vitro. However, such cultured RPE cells easily undergo epithelial-mesenchymal
      transition (EMT) that results in changes of cellular morphology and functions of
      the cells. To restore and maintain the mesenchymal-epithelial transition (MET) of
      the cultured RPE cells, we cultivated dedifferentiated porcine RPE (pRPE) cells
      and compared their behaviors in four conditions: 1) in cell culture dishes with
      DMEM/F12 containing FBS (CC dish-FBS), 2) in petri dishes with DMEM/F12
      containing FBS (Petri dish-FBS), 3) in cell culture dishes with DMEM/F12
      containing N2 and B27 supplements (CC dish-N2B27), and 4) in petri dishes with
      DMEM/F12 containing N2 and B27 (Petri dish-N2B27). In addition to observing the
      cell morphology and behavior, RPE specific markers, as well as EMT-related genes
      and proteins, were examined by immunostaining, quantitative real-time PCR and
      Western blotting. The results showed that dedifferentiated pRPE cells maintained
      EMT in CC dish-FBS, Petri dish-FBS and CC dish-N2B27 groups, whereas MET was
      induced when the dedifferentiated pRPE cells were cultured in Petri dish-N2B27.
      Such induced pRPE cells showed polygonal morphology with increased expression of
      RPE-specific markers and decreased EMT-associated markers. Similar results were
      observed in induced pluripotent stem cell-derived RPE cells. Furthermore, during
      the re-differentiation of those dedifferentiated pRPE cells, Petri dish-N2B27
      reduced the activity of RhoA and induced F-actin rearrangement, which promoted
      the nuclear exclusion of transcriptional co-activator with PDZ-binding motif
      (TAZ) and TAZ target molecule zinc finger E-box binding protein (ZEB1), both of
      which are EMT inducing factors. This study provides a simple and reliable method
      to reverse dedifferentiated phenotype of pRPE cells into epithelialized
      phenotype, which is more appropriate for studying AMD in vitro, and suggests that
      MET of other cell types might be induced by a similar approach.

PMID- 30096325
TI  - Isolation of photoreceptors from mature, developing, and regenerated zebrafish
      retinas, and of microglia/macrophages from regenerating zebrafish retinas.
AB  - This paper describes experimental procedures for the dissociation of retinal
      cells of the zebrafish (Danio rerio) for subsequent fluorescence-activated cell
      sorting (FACS) and gene expression studies. Methods for dissociation of zebrafish
      retinas followed by FACS and RNA isolation were optimized. This methodology was
      applied to isolate pure sorted samples of rods, long wavelength-sensitive (LWS)
      cones, medium wavelength-sensitive (MWS; RH2-2) cones, short wavelength-sensitive
      (SWS2) cones, and UV-sensitive (SWS1) cones from retinas obtained at selective
      life-history stages of the zebrafish, and for some of these photoreceptors,
      following retinal regeneration. We also successfully separated lws1-expressing
      and lws2-expressing LWS cones from fish of a transgenic line in which lws1 is
      reported with green fluorescence protein (GFP) and lws2 is reported with red
      fluorescence protein (RFP). Microglia/macrophages were successfully sorted from
      regenerating retinas (7 days after a cytotoxic lesion) of a transgenic line in
      which these immune cells express GFP. Electropherograms verified downstream
      isolation of high-quality RNA from sorted samples. Examples of post-sorting
      analysis, as well as results of qRT-PCR studies, validated the purity of sorted
      populations. For example, qRT-PCR samples derived from isolated Rh2-2 cones
      contained detectable rh2-2 (opn1mw2) opsin transcripts, but lws opsin transcripts
      (lws1/opn1lw1, lws2/opn1lw2) were not detected, suggesting that the procedure
      likely separated double cone pairs. Through this method, pure, sorted cell
      samples can provide RNA that is reliable for downstream gene expression analyses,
      such as qRT-PCR and RNA-seq, which may reveal molecular signatures of
      photoreceptors and microglia for comparative transcriptomics studies.

PMID- 30096327
TI  - EGFR gene copy number decreases during anti-EGFR antibody therapy in colorectal
      cancer.
AB  - Epidermal growth factor receptor (EGFR) gene copy number (GCN) increase is
      associated with a favourable anti-EGFR antibody treatment response in RAS wild
      type metastatic colorectal cancer. However, there are limited comparative data
      regarding the EGFR GCN in primary colorectal cancer tumours and corresponding
      metastases or the effect of anti-EGFR antibody treatment on EGFR GCN in recurrent
      disease. Additionally, little is known about the potential EGFR GCN changes
      during anti-EGFR therapy in comparison to other treatment regimens. EGFR GCN was
      analysed by EGFR immunohistochemistry guided silver in situ hybridisation in
      primary and corresponding recurrent local or metastatic tumours from 80
      colorectal cancer patients. GCN levels were compared between KRAS wild-type
      patients having received anti-EGFR therapy and patients having received other
      forms of treatment after primary surgery. The EGFR GCN decrease between primary
      and recurrent tumours was more pronounced among the anti-EGFR treated patients
      than patients not treated with anti-EGFR therapy (P = 0.047). None of the
      patients experiencing EGFR GCN increase of >= 1.0 between the primary and
      recurrent tumours were treated with anti-EGFR antibodies. When including only
      patients with distant metastases, EGFR GCN decrease of >= 1.0 was more common
      among the anti-EGFR-treated patients than among patients not treated with anti
      EGFR therapy (P = 0.028). Our results suggest that anti-EGFR antibody treatment
      is associated with EGFR GCN decrease between the primary and recurrent colorectal
      adenocarcinomas, whereas no GCN change is observed among patients receiving other
      forms of treatment after primary surgery.

PMID- 30096328
TI  - Neuronal preservation and reactive gliosis attenuation following neonatal sciatic
      nerve axotomy by a fluorinated cannabidiol derivative.
AB  - Immature peripheral nervous system damage, such as the transection of a
      peripheral nerve, results in the extensive degeneration of motoneurons and dorsal
      root ganglia (DRG) sensory neurons, mostly due to apoptotic events. We have
      previously shown that cannabidiol (CBD), the most abundant non-psychotropic
      molecule present in the Cannabis sativa plant, exhibits neuroprotective action
      when administered daily at a dose of 15 mg/kg. This study shows that use of the
      fluorinated synthetic version of CBD (4'-fluoro-cannabidiol, HUF-101)
      significantly improves neuronal survival by 2-fold compared to that achieved with
      traditional CBD at one-third the dose. Furthermore, we show that HUF-101
      administration significantly upregulates anti-apoptotic genes and blocks the
      expression of pro-apoptotic nuclear factors. Two-day-old Wistar rats were
      subjected to unilateral sectioning of the sciatic nerve and treated daily with
      HUF-101 (1, 2.5, 5 mg/kg/day, i.p.) or a vehicle solution for five days. The
      results were evaluated by Nissl staining, immunohistochemistry, and qRT-PCR.
      Neuronal counting revealed a 47% rescue of spinal motoneurons and a 79% rescue of
      DRG neurons (HUF-101, 5 mg/kg). Survival was associated with complete depletion
      of p53 and a 60-fold elevation in BCL2-like 1 gene expression. Additionally,
      peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene expression was
      downregulated by 80%. Neuronal preservation was coupled with a high preservation
      of synaptic coverage and a reduction in astroglial and microglial reactions that
      were evaluated in nearby spinal motoneurons present in the ventral horn of the
      lumbar intumescence. Overall, these data strongly indicate that HUF-101 exerts
      potent neuroprotective effects that are related to anti-apoptotic protection and
      the reduction of glial reactivity.

PMID- 30096329
TI  - Improving STD service delivery: Would American patients and providers use self
      tests for gonorrhea and chlamydia?
AB  - Chlamydia trachomatis (CT) and Neisseria gonorrhea (GC) are the most frequently
      reported notifiable diseases in the United States and costs for diagnosis and
      treatment of these two infections are approximately $700 million per year. A
      proposed new method for screening for these two infections is self-tests; similar
      to at-home pregnancy and HIV tests which do not include sending collected
      specimens to a laboratory for diagnosis. However, no such self-tests for sexually
      transmitted diseases (STD) have been approved by the Food and Drug Administration
      (FDA). To determine the acceptability of such a test, we used three surveys,
      conducted in 2017, including the American Men's Internet Survey, the SummerStyles
      survey, and the DocStyles survey to ask potential users about their interest in
      this type of test and how they might use it. Among our sampled population of men
      who have sex with men, 79.5% said they would prefer to take this type of test at
      home and 73.9% said they would be willing to pay at least $20 for the test. Among
      young adults (18-29 years), 54.1% indicated that they would like to take this
      test at home and 64.5% were willing to pay more than $10 for such a test. Among
      sampled physicians, 85.1% were "likely" or "very likely" to use an FDA-approved
      STD self-test in their office to screen for CT or GC. Self-tests for STDs are on
      our horizon and we need to be prepared to integrate these tests into our
      healthcare systems.

PMID- 30096331
TI  - Spontaneous resurgence of conditioned fear weeks after successful extinction in
      brain injured mice.
AB  - Mild traumatic brain injury (TBI) is a major risk factor for post-traumatic
      stress disorder (PTSD), and both disorders share common symptoms and
      neurobiological defects. Relapse after successful treatment, known as long-term
      fear resurgence, is common in PTSD patients and a major therapeutic hurdle. We
      induced a mild focal TBI by controlled cortical impact (CCI) in male C57BL/6 J
      mice and used fear conditioning to assess PTSD-like behaviors and concomitant
      alterations in the fear circuitry. We found for the first time that mild TBI, and
      to a lesser extent sham (craniotomy), mice displayed a spontaneous resurgence of
      conditioned fear when tested for fear extinction memory recall, despite having
      effectively acquired and extinguished conditioned fear 6 weeks earlier in the
      same context. Other characteristic symptoms of PTSD are risk-taking behaviors and
      cognitive deficits. CCI mice displayed risk-taking behaviors, behavioral
      inflexibility and reductions in processing speed compared to naive mice. In
      conjunction with these changes there were alterations in amygdala morphology 3
      months post-trauma, and decreased myelin basic protein density at the primary
      lesion site and in distant secondary sites such as the hippocampus, thalamus, and
      amygdala, compared to sham mice. Furthermore, activity-dependent brain-derived
      neurotrophic factor (BDNF) transcripts were decreased in the prefrontal cortex, a
      key region for fear extinction consolidation, following fear extinction training
      in both TBI and, to a lesser extent, sham mice. This study shows for the first
      time that a mild brain injury can generate a spontaneous resurgence of
      conditioned fear associated with defective BDNF signalling in the prefrontal
      cortex, PTSD-like behaviors, and have enduring effects on the brain.

PMID- 30096330
TI  - Long-term impact of chronic variable stress in adolescence versus adulthood.
AB  - Adolescence is a period of active development of stress regulatory
      neurocircuitry. As a consequence, mechanisms that control the responses to stress
      are not fully matured during this developmental period, which may result in
      vulnerability to chronic stress. We hypothesized that adolescent chronic stress
      would have negative consequences on stress adaptation later in life. Male Wistar
      rats (PND40) were subjected to chronic variable stress (CVS) for 2 weeks, with 2
      daily stressors randomly presented and overnight social stressors twice a week.
      After five weeks, animals were evaluated during adulthood, using the elevated
      plus maze (EPM) and the forced swim test (FST). The hypothalamic-pituitary
      adrenal (HPA) axis response to a 30-min restraint was also assessed. Results are
      compared to those of adult rats tested 5 weeks following CVS cessation. Our
      results demonstrate that the long-term effects of CVS are specific to the age of
      application of the stress regime. We show how behavior and HPA axis response as
      well as hypothalamic paraventricular nucleus activation can differ with age,
      resulting in differential behavioral adaptations for animals stressed in
      adolescence and dysregulation of the HPA axis in the animals stressed in
      adulthood, These data underscore the importance of the adolescent period in
      determining resilience of the HPA axis and programming behavioral responses later
      in life.

PMID- 30096333
TI  - Authors' reply.

PMID- 30096332
TI  - Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline
      containing regimens and undergoing adjunctive surgery.
AB  - OBJECTIVES: No study evaluated the contribution of adjunctive surgery in
      bedaquiline-treated patients. This study describes treatment outcomes and
      complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases
      treated with bedaquiline-containing regimens undergoing surgery. METHODS: This
      retrospective observational study recruited patients treated for TB in 12 centres
      in 9 countries between January 2007 and March 2015. Patients who had surgical
      indications in a bedaquiline-treated programme-based cohort were selected and
      surgery-related information was collected. Patient characteristics and surgical
      indications were described together with type of operation, surgical
      complications, bacteriological conversion rates, and treatment outcomes.
      Treatment outcomes were evaluated according to the time of surgery. RESULTS: 57
      bedaquiline-exposed cases resistant to a median of 7 drugs had indication for
      surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB).
      Sixty percent of cases initiated bedaquiline treatment following surgery, while
      36.4% underwent the bedaquiline regimen before surgery and completed it after the
      operation. At treatment completion 90% culture-converted with 69.1% achieving
      treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8%
      lost to follow-up), and 9.1% were still undergoing treatment. CONCLUSIONS: The
      study results suggest that bedaquiline and surgery can be safely and effectively
      combined in selected cases with a specific indication.

PMID- 30096334
TI  - Female-biased population divergence in the venom of the Hentz striped scorpion
      (Centruroides hentzi).
AB  - Sex-biased genes are expressed at higher levels in one sex and contribute to
      phenotypic differences between males and females, as well as overall phenotypic
      variation within and among populations. Venom has evolved primarily for predation
      and defense, making venom expression a highly variable phenotype as a result of
      local adaptation. Several scorpion species have shown both intraspecific and
      intersexual venom variation, and males have been observed using venom in
      courtship and mating, suggesting the existence of venom-specific, sex-biased
      genes that may contribute to population divergence. We used reversed-phase high
      performance liquid chromatography (RP-HPLC), Agilent protein bioanalyzer chips,
      nano-liquid chromatography mass spectrometry (nLC/MS/MS), and median lethal dose
      (LD50) assays in fruit flies (Drosophila melanogaster) and banded crickets
      (Gryllodes sigillatus) to investigate proteomic and functional venom variation
      within and among three Florida populations of the Hentz striped scorpion
      (Centruroides hentzi). We found significant venom variation among populations,
      with females, not males, being responsible for this divergence. We also found
      significant variation in venom expression within populations, with males
      contributing more to within population variation than females. Our results
      provide evidence that male and female scorpions experience different natural and
      sexual selective pressures that have led to the expression of sex-biased venom
      genes and that these genes may be consequential in population divergence.

PMID- 30096302
TI  - Comprehensive Characterization of Cancer Driver Genes and Mutations.

PMID- 30096335
TI  - Dynamics of a magnetically rotated micro swimmer inspired by paramecium
      metachronal wave.
AB  - In the past few years, a significant body of research has been devoted to
      designing magnetic micron scale robotic systems for minimally invasive medicine.
      The motion of different microorganisms is the nature's solution for efficient
      propulsion of these swimmers. So far, there has been a considerable effort in
      designing micro swimmers based on the propulsion of bacteria while the motion of
      numerous other microorganisms has not been a source of inspiration for designing
      micro swimmers yet. Inspired by propulsion of Paramecium which is a ciliate
      microorganism, a novel micro swimmer is proposed in this article which is capable
      of cargo transport. This novel swimmer is composed of multiple equally spaced
      rigid loxodromic rods spanning the surface of a sphere which can carry a cargo
      placed inside it. The propulsion of this swimmer is influenced by the geometry of
      the swimmer (diameter, number of rods, cargo size), therefore, CFD simulations
      have been performed to investigate it. Finally, the dynamics of this swimmer is
      investigated analytically which sheds light into the complex dynamics of a
      swimmer with this geometry.

PMID- 30096337
TI  - Identification and functional characterization of amphioxus Miple, ancestral type
      of vertebrate midkine/pleiotrophin homologues.
AB  - Midkine (MK) and pleiotrophin (PTN) are the only two members of heparin-binding
      growth factor family. MK/PTN homologues found from Drosophila to humans are shown
      to have antibacterial activities and their antibacterial domains are conserved
      during evolution. However, little is known about MK/PTN homologue in the basal
      chordate amphioxus, and overall, information regarding MK/PTN homologues is
      rather limited in invertebrates. In this study, we identified a single MK/PTN
      homologue in Branchiostoma japonicum, termed BjMiple, which has a novel domain
      structure of PTN-PTNr1-PTNr2, and represents the ancestral form of vertebrate
      MK/PTN family proteins. BjMiple was expressed mainly in the ovary in a tissue
      dependent fashion, and its expression was remarkably up-regulated following
      challenge with bacteria or their signature molecules LPS and LTA, suggesting its
      involvement in antibacterial responses. Functional assays revealed that BjMiple
      had strong antimicrobial activity, capable of killing a panel of Gram-negative
      and Gram-positive bacteria via a membranolytic mechanism, including interaction
      with bacterial membrane via LPS and LTA, membrane depolarization and high
      intracellular levels of ROS. Importantly, strong antibacterial activity was
      localized in PTN42-61 and PTNr142-66. Additionally, BjMiple and its derived
      peptides PTN42-61 and PTNr142-66 were not cytotoxic to human RBCs and mammalian
      cells. Taken together, our study suggests that amphioxus Miple is the ancestral
      type of vertebrate MK/PTN family homologues, and can play important roles as
      innate peptide antibiotics, which renders it a promising template for the design
      of novel peptide antibiotics against multi-drug resistant bacteria.

PMID- 30096338
TI  - A comprehensive analysis of the genomic organization, expression and phylogeny of
      immunoglobulin light chain genes in pigeon (Columba livia).
AB  - Previous studies on immunoglobulin light chain (IgL) genes in avian species are
      limited to Galloanseres, and few studies have investigated IgL genes in Neoaves,
      which includes most living birds. Based on published genome data, we demonstrate
      that the pigeon (Columba livia) IgL locus spans approximately 24 kb of DNA and
      contains twenty Vlambda segments located upstream of a single pair of Jlambda
      Clambda. Among the identified Vlambda gene segments, four segments are
      structurally intact and all four segments are able to recombine with Jlambda.
      Moreover, the four functional Vlambda segments are preferentially utilized in
      VlambdaJlambda recombination. Phylogenetic analysis suggests that the presence of
      the four functional Vlambda segments in pigeon was likely generated by gene
      duplication that occurred after the divergence of pigeon and other birds. Our
      study provides insight into IgL gene evolution and evolutionary diversity of Ig
      genes in birds.

PMID- 30096340
TI  - Inhibition of adenovirus serotype 14 infection by octadecyloxyethyl esters of (S)
      [(3-hydroxy-2-phosphonomethoxy)propyl]- nucleosides in vitro.
AB  - On September 22, 2008, a physician on Prince of Wales Island, Alaska, notified
      the Alaska Department of Health and Social Services (ADHSS) of an unusually high
      number of adult patients with recently diagnosed pneumonia (n = 10), including
      three persons who required hospitalization and one who died. ADHSS and CDC
      conducted an investigation to determine the cause and distribution of the
      outbreak, identify risk factors for hospitalization, and implement control
      measures. This report summarizes the results of that investigation, which found
      that the outbreak was caused by adenovirus 14 (Ad14), an emerging adenovirus
      serotype in the United States that is associated with a higher rate of severe
      illness compared with other adenoviruses. Among the 46 cases identified in the
      outbreak from September 1 through October 27, 2008, the most frequently observed
      characteristics included the following: male (70%), Alaska Native (61%),
      underlying pulmonary disease (44%), aged > or = 65 years (26%), and current
      smoker (48%). Patients aged > or = 65 years had a fivefold increased risk for
      hospitalization. The most commonly reported symptoms were cough (100%), shortness
      of breath (87%), and fever (74%). Of the 11 hospitalized patients, three required
      intensive care, and one required mechanical ventilation. One death was reported.
      Ad14 isolates obtained during the outbreak were identical genetically to those in
      recent community-acquired outbreaks in the United States which suggests the
      emergence of a new, and possibly more virulent Ad14 variant. Clinicians should
      consider Ad14 infection in the differential diagnosis for patients with community
      acquired pneumonia, particularly when unexplained clusters of severe respiratory
      infections are detected.

PMID- 30096339
TI  - Alkyl-imino sugars inhibit the pro-oncogenic ion channel function of human
      papillomavirus (HPV) E5.
AB  - Despite the availability of prophylactic vaccines the burden of human
      papillomavirus (HPV) associated malignancy remains high and there is a need to
      develop additional therapeutic strategies to complement vaccination. We have
      previously shown that the poorly characterised E5 oncoprotein forms a virus-coded
      ion channel or viroporin that was sensitive to the amantadine derivative
      rimantadine. We now demonstrate that alkylated imino sugars, which have antiviral
      activity against a number of viruses, inhibit E5 channel activity in vitro. Using
      molecular modelling we predict that imino sugars intercalate between E5 protomers
      to prevent channel oligomerisation. We explored the ability of these viroporin
      inhibitors to block E5-mediated activation of mitogenic signalling in
      keratinocytes. Treatment with either rimantadine or imino sugars prevented ERK
      MAPK phosphorylation and reduced cyclin B1 expression in cells expressing E5 from
      a number of high-risk HPV types. Moreover, viroporin inhibitors also reduced ERK
      MAPK activation and cyclin B1 expression in differentiating primary human
      keratinocytes containing high-risk HPV18. These observations provide evidence of
      a key role for E5 viroporin function during the HPV life cycle. Viroporin
      inhibitors could be utilised for stratified treatment of HPV associated tumours
      prior to virus integration, or as true antiviral therapies to eliminate virus
      prior to malignant transformation.

PMID- 30096336
TI  - Phage therapy for respiratory infections.
AB  - A respiratory infection caused by antibiotic-resistant bacteria can be life
      threatening. In recent years, there has been tremendous effort put towards
      therapeutic application of bacteriophages (phages) as an alternative or
      supplementary treatment option over conventional antibiotics. Phages are natural
      parasitic viruses of bacteria that can kill the bacterial host, including
      antibiotic-resistant bacteria. Inhaled phage therapy involves the development of
      stable phage formulations suitable for inhalation delivery followed by
      preclinical and clinical studies for assessment of efficacy, pharmacokinetics and
      safety. We presented an overview of recent advances in phage formulation for
      inhalation delivery and their efficacy in acute and chronic rodent respiratory
      infection models. We have reviewed and presented on the prospects of inhaled
      phage therapy as a complementary treatment option with current antibiotics and as
      a preventative means. Inhaled phage therapy has the potential to transform the
      prevention and treatment of bacterial respiratory infections, including those
      caused by antibiotic-resistant bacteria.

PMID- 30096342
TI  - A review on silver nanoparticles-induced ecotoxicity and the underlying toxicity
      mechanisms.
AB  - Silver nanoparticles (Ag-NPs) are increasingly being applied in many consumer
      products due to their unique properties. Widespread use of Ag-NPs leads to an
      increasing human exposure to Ag-NPs in many different pathways. This review
      summarized the toxicity mechanisms of Ag-NPs based on various environmentally
      relevant test species, such as bacteria, cells, plants, aquatic animals and
      mammals, in both in vitro and in vivo experiments. Nanoparticles were usually
      exposed to combination chemicals but to single chemicals in the environment and
      thereby exert combined toxicities to the organisms. Therefore, the joint effects
      of nanomaterials and their co-existing characteristics were also discussed. The
      current knowledge gaps and safe product designs of Ag-NPs have been discussed in
      detail. The limited and existing data implied that understanding the toxicity
      mechanisms is crucial to the future research development of nanomaterials.

PMID- 30096341
TI  - Optimization of Agrobacterium tumefaciens-mediated transformation method of
      oleaginous filamentous fungus Mortierella alpina on co-cultivation materials
      choice.
AB  - The Agrobacterium tumefaciens-mediated transformation (ATMT) method is commonly
      applied in the oleaginous filamentous fungus Mortierella alpina. During the ATMT
      process, the spores of M. alpina have traditionally been used as a co-cultivation
      material, but their long spore-producing cycle and low sporulation rate make the
      transformation process tedious. This study explores the use of germinating
      spores, mycelium and single solid colonies of uracil auxotrophic M. alpina
      CCFM501 as a co-cultivation material with A. tumefaciens AGL1. The results show
      that A. tumefaciens AGL1 can successfully transform the germinating spores,
      mycelium and single solid colonies of M. alpina. In addition, the transformation
      rate of the germinating spores was 50% higher than that of the fresh spores. Due
      to its concise preparation process, the mycelium was chosen as a co-cultivation
      material for two plasmids of different lengths and proven to be an efficient co
      cultivation material for M. alpina.

PMID- 30096343
TI  - An automated mapping method for Nissl-stained mouse brain histologic sections.
AB  - BACKGROUND: Histologic evaluation of the central nervous system is often a
      critical endpoint in in vivo efficacy studies, and is considered the essential
      component of neurotoxicity assessment in safety studies. Automated image analysis
      is a powerful tool that can radically reduce the workload associated with
      evaluating brain histologic sections. NEW METHOD: We developed an automated brain
      mapping method that identifies neuroanatomic structures in mouse histologic
      coronal brain sections. The method utilizes the publicly available Allen Brain
      Atlas to map brain regions on digitized Nissl-stained sections. RESULTS: The
      method's accuracy was first assessed by comparing the mapping results to
      structure delineations from the Franklin and Paxinos (FP) mouse brain atlas.
      Brain regions mapped from FP Nissl-stained sections and calculated volumes were
      similar to structure delineations and volumes derived from corresponding FP
      illustrations. We subsequently applied our method to mouse brain sections from an
      in vivo study where the hippocampus was the structure of interest. Nissl-stained
      sections were mapped and hippocampal boundaries transferred to adjacent
      immunohistochemically stained sections. Optical density quantification results
      were comparable to those from time-consuming, manually drawn hippocampal
      delineations on the IHC-stained sections. COMPARISON WITH EXISTING METHODS:
      Compared to other published methods, our method requires less manual input, and
      has been validated comprehensively using a secondary atlas, as well as manually
      annotated brain IHC sections from 68 study mice. CONCLUSIONS: We propose that our
      automated brain mapping method enables greater efficiency and consistency in
      mouse neuropathologic assessments.

PMID- 30096344
TI  - Impact of silver, gold, and iron oxide nanoparticles on cellular response to
      tumor necrosis factor.
AB  - Metallic nanomaterials are utilized in an increasing number of applications in
      medicine and industry. Their general toxicity was tested in numerous reports both
      in vitro and in vivo but limited data exist on how nanomaterials affect the
      activity of cellular signaling pathways activated by growth factors and
      cytokines. The aim of the present work was to test the hypothesis predicting that
      silver, gold and superparamagnetic iron oxide nanoparticles may interfere with
      cellular signaling activated by tumor necrosis factor (TNF) and change the final
      cellular outcome of TNF action. Such interference may result in disruption of
      homeostasis and contribute to the development of malignancies such as cancer or
      autoimmune diseases. Experiments were performed on HepG2 and A549 cell lines. We
      did not observe any interaction between nanoparticles and TNF at the level of
      clonogenic growth, apoptosis/necrosis induction or cell cycle. At all these
      endpoints, the effects of TNF and nanoparticles were additive. In contrast, gene
      expression analysis revealed synergistic effects. A group of genes was
      significantly affected only by simultaneous treatment with TNF and nanoparticles
      and not by any of the factors alone. Observed synergistic effect on IL10 and IL8
      expression seems to be of particular importance since these cytokines are often
      expressed by tumor cells to inhibit tumor-targeted immune response. The observed
      synergistic effects of TNF and nanoparticles on cytokines expression may have
      significant consequences for tissue homeostasis and tumor promotion and therefore
      should be taken into account during development of new nanoparticle-based
      anticancer therapies.

PMID- 30096345
TI  - Results of a randomized controlled trial evaluating the effect of increasing
      package size on usage volume of peanut butter in older adults.
AB  - BACKGROUND: Portion and package sizes of foods generally influence energy intake
      in children and adults. However, little is known about this effect in older
      adults. This study aimed to determine the effect of increasing package size on
      usage volume of peanut butter in older adults. Furthermore, it is investigated
      whether older women and men, different age groups (<65, 65-80, and 80+), and non
      overweight (BMI<25), overweight (BMI>=25) and obese (BMI>30) older adults had
      different responses to variation in package size. METHODS: A randomized
      controlled trial among 205 older adults was conducted wherein participants were
      randomized to either the small (350 g) (n = 103) or the large (1000 g) (n = 102)
      package size condition. Linear regression analyses were used to determine the
      association between package size condition and usage volume of peanut butter on a
      slice of bread. Interactions of sex, age groups and BMI categories with package
      size were tested to investigate differences in responses to variation in package
      size. RESULTS: Older adults spread on average 12.4 g (SD = 4.3) of peanut butter
      on a slice of bread when exposed to a small jar of peanut butter and 12.6 g (SD =
      4.4) when exposed to a large jar of peanut butter (B = 0.15; 95%CI = -1.04 to
      1.35). Interactions between sex, age groups or BMI categories with package size
      condition were not statistically significant. CONCLUSIONS: Increased package size
      has no effect on usage volume of peanut butter among older adults. Older women
      and men, different age groups within older adults, and normal-weight, overweight
      and obese older adults do not respond differently to variation in package size of
      spreads.

PMID- 30096346
TI  - The P Granules of C. elegans: A Genetic Model for the Study of RNA-Protein
      Condensates.
AB  - P granules are RNA/protein condensates in the germline of Caenorhabditis elegans.
      Genetic analyses have begun to identify the proteins that regulate P granule
      assembly in the cytoplasm of zygotes. Among them, the RGG-domain protein PGL-3,
      the intrinsically disordered protein MEG-3, and the RNA helicase LAF-1 all bind
      and phase separate with RNA in vitro. We discuss how RNA-induced phase
      separation, competition with other RNA-binding proteins, and reversible
      phosphorylation contribute to the asymmetric localization of P granules in the
      cytoplasm of newly fertilized embryos. P granules contain RNA silencing complexes
      that monitor the germline transcriptome and may provide an RNA memory of germline
      gene expression across generations.

PMID- 30096347
TI  - Probing Structural Changes during Self-assembly of Surface-Active Hydrophobin
      Proteins that Form Functional Amyloids in Fungi.
AB  - Hydrophobins are amphiphilic proteins secreted by filamentous fungi in a soluble
      form, which can self-assemble at hydrophilic/hydrophobic or water/air interfaces
      to form amphiphilic layers that have multiple biological roles. We have
      investigated the conformational changes that occur upon self-assembly of six
      hydrophobins that form functional amyloid fibrils with a rodlet morphology. These
      hydrophobins are present in the cell wall of spores from different fungal
      species. From available structures and NMR chemical shifts, we established the
      secondary structures of the monomeric forms of these proteins and monitored their
      conformational changes upon amyloid rodlet formation or thermal transitions using
      synchrotron radiation circular dichroism and Fourier-transform infrared
      spectroscopy (FT-IR). Thermal transitions were followed by synchrotron radiation
      circular dichroism in quartz cells that allowed for microbubbles and hence
      water/air interfaces to form and showed irreversible conformations that differed
      from the rodlet state for most of the proteins. In contrast, thermal transitions
      on hermetic calcium fluoride cells showed reversible conformational changes.
      Heating hydrophobin solutions with a water/air interface on a silicon crystal
      surface in FT-IR experiments resulted in a gain in beta-sheet content typical of
      amyloid fibrils for all except one protein. Rodlet formation was further
      confirmed by electron microscopy. FT-IR spectra of pre-formed hydrophobin rodlet
      preparations also showed a gain in beta-sheet characteristic of the amyloid cross
      beta structure. Our results indicate that hydrophobins are capable of significant
      conformational plasticity and the nature of the assemblies formed by these
      surface-active proteins is highly dependent on the interface at which self
      assembly takes place.

PMID- 30096348
TI  - Penile Median Raphe Anomalies as an Indicator of Megameatus Intact Prepuce
      Anomaly in Children Undergoing Routine Circumcision.
AB  - OBJECTIVE: To arouse the suspicious for early diagnosis and hence, proper
      management of megameatus with an intact prepuce (MIP), as there is no external
      clue for detection of such cases, which usually come to light for the first time
      in a boy who is about to retract his prepuce or during neonatal circumcision.
      MATERIALS AND METHODS: Examination of neonates and infants coming to circumcision
      clinic to detect congenital genitourinary anomalies. Evaluation of 12,518
      neonates and infants coming for ritual circumcision from 2006-2017, who were
      examined thoroughly to detect any incidental congenital genitourinary anomalies.
      Fifteen of them were diagnosed to have a MIP anomaly. They were investigated to
      perceive any associated median raphe (MR) anomalies. Sensitivity, positive
      predictive value, specificity, and negative predictive value of MR anomalies in
      cases of MIP were estimated and compared with other children who had a normally
      positioned meatus. RESULTS: Overall incidence of MIP in this group of babies was
      0.12%. Twelve of 15 cases (80%) with MIP had 19 forms of MR anomalies; mainly
      raphe deviation in 6 cases, hyperpigmented raphe in 6, prominent raphe in 4, and
      bifurcation in 3 cases. Three cases had a redundant long prepuce, and 1 had
      paraphimosis after preputial retraction, otherwise no other genitourinary
      anomalies could be detected in those cases. CONCLUSION: MR anomalies, mainly
      deviation and hyperpigmented prominent raphe, are significant indictors for the
      presence of an invisible MIP anomaly. Abnormally redundant long prepuce may be
      seen in such cases, but this is not common.

PMID- 30096349
TI  - Development of a real time loop-mediated isothermal amplification method for
      detection of Senecavirus A.
AB  - Senecavirus A (SVA), formerly known as Seneca Valley Virus (SVV), is one of
      causative agents of vesicular diseases in swine. Recently, the outbreaks
      associated with vesicular disease caused by SVA infection in pig herds have been
      reported in Brazil, USA, China, Thailand and Canada. Several molecular detection
      methods have been established to determine the infection of SVA, including real
      time reverse transcription PCR assay, nested PCR, a TaqMan-based qRT-PCR assay
      and RNA-based in situ hybridization method. In our study, an assay for the
      identification of SVA in pig herds using real time reverse transcription loop
      mediated isothermal amplification (real time RT-LAMP) was developed. The limit of
      detection for the assay was 1 TCID50/ml. One hundred and eighteen field samples
      from pigs were used to validate the assay for clinical application. Our result
      demonstrated that real time RT-LAMP assay is a cost-effective and highly specific
      and sensitive alternative for the rapid detection of SVA in clinical samples.

PMID- 30096350
TI  - Comparison of somatic and F+ coliphage enumeration methods with large volume
      surface water samples.
AB  - Coliphages are alternative fecal indicators that may be suitable surrogates for
      viral pathogens, but majority of standard detection methods utilize insufficient
      volumes for routine detection in environmental waters. We compared three somatic
      and F+ coliphage methods based on a paired measurement from 1 L samples collected
      from the Great Lakes (n = 74). Methods include: 1) dead-end hollow fiber
      ultrafilter with single agar layer (D-HFUF-SAL); 2) modified SAL (M-SAL); and 3)
      direct membrane filtration (DMF) technique. Overall, D-HFUF-SAL outperformed
      other methods as it yielded the lowest frequency of non-detects [(ND); 10.8%] and
      the highest average concentrations of recovered coliphage for positive samples
      (2.51 +/- 1.02 [standard deviation, SD] log10 plaque forming unit/liter (PFU/L)
      and 0.79 +/- 0.71 (SD) log10 PFU/L for somatic and F+, respectively). M-SAL
      yielded 29.7% ND and average concentrations of 2.26 +/- 1.15 (SD) log10 PFU/L
      (somatic) and 0.59 +/- 0.82 (SD) log10 PFU/L (F+). DMF performance was inferior
      to D-HFUF-SAL and M-SAL methods (ND of 65.6%; average somatic coliphage
      concentration 1.52 +/- 1.32 [SD] log10 PFU/L, no F+ detected), indicating this
      procedure is unsuitable for 1 L surface water sample volumes. This study
      represents an important step toward the use of a coliphage method for
      recreational water quality criteria purposes.

PMID- 30096351
TI  - Genome Editing of Human Primary Keratinocytes by CRISPR/Cas9 Reveals an Essential
      Role of the NLRP1 Inflammasome in UVB Sensing.
AB  - By forming a protective barrier, epidermal keratinocytes represent the first line
      of defense against environmental insults. UVB radiation of the sun is a major
      challenge for the skin and can induce inflammation, aging, and eventually skin
      cancer. UVB induces an immune response in human keratinocytes resulting in
      activation and secretion of the proinflammatory cytokines proIL-1beta and -18.
      This is mediated by an assembly of protein complexes, termed inflammasomes.
      However, the mechanisms underlying sensing of UVB by keratinocytes, and
      particularly the types of inflammasomes required for cytokine secretion, are a
      matter of debate. To address these questions, we established a protocol that
      allows the generation of CRISPR/Cas9-targeted human primary keratinocytes. Our
      experiments showed an essential role of the NLRP1 rather than the NLRP3
      inflammasome in UVB sensing and subsequent IL-1beta and -18 secretion by
      keratinocytes. Moreover, NLRP1 but not NLRP3 was required for inflammasome
      activation in response to nigericin, a potassium ionophore and well-established
      NLRP3 activator in immune cells. Because the CRISPR/Cas9-targeted cells retained
      their full differentiation capacity, genome editing of human primary
      keratinocytes might be useful for numerous research and medical applications.

PMID- 30096352
TI  - Preparation of New Risperidone Depot Microspheres Based on Novel Biocompatible
      Poly(Alkylene Adipate) Polyesters as Long-Acting Injectable Formulations.
AB  - Risperidone (RIS)-loaded microspheres based on poly(alkylene adipate)s derived
      from dicarboxylic acids and different aliphatic diols were prepared by the oil in
      water emulsion and solvent evaporation method. Specifically, 3 polyesters, namely
      poly(ethylene adipate), poly(propylene adipate), and poly(butylene adipate), were
      prepared with the aid of a 2-stage melt-polycondensation method and characterized
      by gel permeation chromatography, proton nuclear magnetic resonance (1H NMR),
      differential scanning calorimetry, and X-ray diffraction analysis. Results showed
      that the molecular weight of the polyesters increased as the diol molecular
      weight increased, while all polymers were of semi-crystalline nature and the
      melting temperature was varying from 49.1 degrees C to 51.8 degrees C and 65.9
      degrees C for poly(propylene adipate), poly(ethylene adipate), and poly(butylene
      adipate), respectively. The particle size of the RIS-loaded microspheres varied
      from 10 to 100 MUm depending on the polyester type and the drug loading, while X
      ray diffraction analysis revealed amorphous active pharmaceutical ingredient in
      the cases of high drug-loaded microspheres. In vitro drug release studies along
      with scanning electron microscopy images of microspheres after the completion of
      dissolution process showed that in all cases RIS release was controlled by the
      glass transition temperature of polyesters and physical state of active
      pharmaceutical ingredients via diffusion.

PMID- 30096353
TI  - Physical and Biochemical Characterization of Chemically Treated Pollen Shells for
      Potential Use in Oral Delivery of Therapeutics.
AB  - Allergen-free pollen shells obtained from natural pollen grains have recently
      attracted attention as microcapsules for oral therapeutic delivery. We have
      recently developed a chemical treatment method that enables successful retrieval
      of hollow pollen shells from diverse species. A comprehensive characterization is
      critical to characterize the effects of chemical treatment which will not only
      benchmark the pollen treatment process but can also lay the foundation of quality
      control procedures to check allergen-removal efficiency during pollen treatment.
      Therefore, in this study, we followed the effects of chemical treatment on 4
      different pollen species using electron microscopy, elemental analysis, gel
      electrophoresis, confocal microscopy, Fourier-transform infrared spectroscopy,
      and thermogravimetric analysis. These analyses revealed that acetone treatment
      removed lipids from the pollen surface. Phosphoric acid treatment removed
      proteins and nucleic acids from the pollen core and transformed esters into
      carboxylic acids. Potassium hydroxide hydrolysis changed carbohydrate composition
      of the pollen wall. Chemically treated pollen shells exhibited hydroxyl and
      carboxyl functional groups on their surface. Overall, we propose that confocal
      microscopy could be used as a rapid scanning technique to visualize the removal
      of biomolecules, whereas Fourier-transform infrared combined with gel
      electrophoresis could be used as a more objective approach for analysis and
      benchmarking.

PMID- 30096354
TI  - Rationale and Application of the Protocol S Anti-Vascular Endothelial Growth
      Factor Algorithm for Proliferative Diabetic Retinopathy.
AB  - PURPOSE: To present the rationale, guidelines, and results of ranibizumab
      treatment for proliferative diabetic retinopathy (PDR) in Diabetic Retinopathy
      Clinical Research Network (DRCR.net) Protocol S. DESIGN: Post hoc analyses from a
      randomized clinical trial. PARTICIPANTS: Three hundred five participants (394
      study eyes) having PDR without prior panretinal photocoagulation (PRP). METHODS:
      Intravitreous ranibizumab (0.5 mg) versus PRP for PDR. Ranbizumab-assigned eyes
      (n = 191) received monthly injections for 6 months unless resolution was achieved
      after 4 injections. After 6 months, injections could be deferred if
      neovascularization was stable over 3 consecutive visits (sustained stability). If
      neovascularization worsened, monthly treatment resumed. Panretinal
      photocoagulation could be initiated for failure or futility criteria. MAIN
      OUTCOME MEASURES: Neovascularization status through 2 years. RESULTS: At 1 month,
      19% (35 of 188) of ranibizumab-assigned eyes showed complete neovascularization
      resolution and an additional 60% (113) showed improvement. At 6 months, 52% (80
      of 153) showed neovascularization resolution, 3% (4) were improved, 37% (56) were
      stable, and 8% (13) had worsened since the last visit. Among eyes with versus
      without resolved neovascularization at 6 months, the median (interquartile range)
      number of injections between 6 months and 2 years was 4 (1-7; n = 73) versus 7 (4
      11; n = 67; P < 0.001). Injections were deferred in 68 of 73 eyes (93%) meeting
      sustained stability at least once during the study; 62% (42 of 68) resumed
      injections within 16 weeks after deferral. At 2 years, 43% (66 of 154) showed
      neovascularization resolution, 5% (7) showed improvement, 23% (36) were stable,
      and 27% (42) had worsened since the last visit. Only 3 eyes met criteria for
      failure or futility through 2 years. CONCLUSIONS: The DRCR.net treatment
      algorithm for PDR can provide excellent clinical outcomes through 2 years for
      patients initiating anti-vascular endothelial growth factor (VEGF) therapy for
      PDR. When choosing between anti-VEGF and PRP as first-line therapy for PDR,
      treatment decisions should be guided by consideration of the relative advantages
      of each therapeutic method and anticipated patient compliance with follow-up and
      treatment recommendations.

PMID- 30096355
TI  - Polio priority countries and the 2018 Hajj: Leveraging an opportunity.

PMID- 30096356
TI  - Statistical mistakes and how to avoid them - lessons learned from the
      reproducibility crisis.

PMID- 30096357
TI  - Validation of high-resolution melting analysis as a diagnostic tool for
      endothelin receptor B mutation in American Paint horses and allele frequency
      estimation.
AB  - Overo lethal white foal syndrome (OLWFS) is a genetic disorder caused by a
      dinucleotide mutation in the endothelin receptor type B (EDNRB) gene leading to
      the death of affected foals shortly after birth. The use of rapid and reliable
      genetic testing is imperative for the early diagnosis of the mutation avoiding,
      therefore, either additional suffering or the production of affected animals. In
      the present study, we developed and validated a high-resolution melting (HRM)
      genotyping assay to detect the OLWFS causative mutation, and we also determined
      the frequency of heterozygotes among American Paint horses in Brazil. The HRM
      genotyping assay resulted in a high sensitivity, specificity, and positive and
      negative predictive values. The overall estimated frequency of heterozygotes was
      21.6%; however, this frequency increased to 89.5% when considering only overo
      horses. The HRM assay optimized here was a reliable and suitable method for the
      detection of the dinucleotide mutation observed in the EDNRB gene resulting in a
      fast, accurate, and precise diagnostic tool. The causative gene mutation of OLWFS
      is present in heterozygosity in the American Paint Horse population in Brazil and
      is highly frequent among overo horses.

PMID- 30096358
TI  - Serosurveillance of avian influenza A/H5N6 virus infection in poultry farmers,
      Gyeonggi Province, Republic of Korea, 2016-2017.
AB  - OBJECTIVES: Between November 20, 2016 and April 17, 2017, outbreaks of highly
      pathogenic avian influenza (HPAI) A/H5N6 occurred on poultry farms in Gyeonggi
      Province in the Republic of Korea. A serosurvey was conducted among poultry
      farmers to identify the transmission of HPAI A/H5N6 virus to humans. METHODS: A
      descriptive study of 870 poultry farmers in Gyeonggi Province in Korea was
      conducted during the 2016-2017 outbreaks. Serological testing was performed using
      a microneutralization (MN) assay for antibodies against influenza
      A/duck/ES2/Korea/2016 virus, which has antigenic properties similar to those of
      the HPAI A/H5N6 virus that caused this poultry outbreak. RESULTS: Overall, 523
      exposed poultry farmers were assessed by serological testing. Consequently, all
      tested negative for HPAI A/H5N6 virus via MN assay. CONCLUSIONS: Based on
      serological assays, no transmission of HPAI A/H5N6 to humans was identified in
      this study cohort. Additional studies should be conducted to determine the
      possibility of poultry-to-human transmission of HPAI A/H5N6.

PMID- 30096359
TI  - Mesenteric lymphadenitis as a presenting feature of Whipple's disease: Value of
      PCR analysis.
AB  - Whipple's disease (WD) is a rare chronic and systemic infection caused by the
      ubiquitous actinomycete Tropheryma whipplei. A case of localized infection with
      mesenteric adenopathy associated with a prolonged unexplained fever is reported
      herein. Screening by PCR on saliva and stool was positive, and T. whipplei was
      formally identified by specific PCR on duodenal and mesenteric adenopathy
      biopsies. Histological analysis did not demonstrate periodic acid-Schiff-positive
      macrophages or positive T. whipplei immunochemistry in either the duodenal mucosa
      or mesenteric nodes. Treatment with hydroxychloroquine and doxycycline allowed a
      rapid resolution of symptoms, and subsequent saliva and stool PCR results were
      negative.

PMID- 30096360
TI  - The heparanase inhibitor PG545 is a potent anti-lymphoma drug: Mode of action.
AB  - It is now well recognized that heparanase, an endo-beta-D-glucuronidase capable
      of cleaving heparan sulfate (HS) side chains at a limited number of sites,
      promotes tumorigenesis by diverse mechanisms. Compelling evidence strongly
      implies that heparanase is a viable target for cancer therapy, thus encouraging
      the development of heparanase inhibitors as anti-cancer therapeutics. Here, we
      examined the efficacy and mode of action of PG545, an HS-mimetic heparanase
      inhibitor, in human lymphoma. We found that PG545 exhibits a strong anti-lymphoma
      effect, eliciting lymphoma cell apoptosis. Notably, this anti-lymphoma effect
      involves ER stress response that was accompanied by increased autophagy. The
      persistent ER stress evoked by PG545 is held responsible for cell apoptosis
      because apoptotic cell death was attenuated by an inhibitor of PERK, a molecular
      effector of ER stress. Importantly, PG545 had no such apoptotic effect on naive
      splenocytes, further encouraging the development of this compound as anti
      lymphoma drug. Surprisingly, we found that PG545 also elicits apoptosis in
      lymphoma cells that are devoid of heparanase activity (i.e., Raji), indicating
      that the drug also exerts heparanase-independent function(s) that together
      underlie the high potency of PG545 in preclinical cancer models.

PMID- 30096361
TI  - Association between genetic variability of neuronal nitric oxide synthase and
      sensorimotor gating in humans.
AB  - Research increasingly suggests that nitric oxide (NO) plays a role in the
      pathogenesis of schizophrenia. One important line of evidence comes from genetic
      studies, which have repeatedly detected an association between the neuronal
      isoform of nitric oxide synthase (nNOS or NOS1) and schizophrenia. However, the
      pathogenetic pathways linking nNOS, NO, and the disorder remain poorly
      understood. A deficit in sensorimotor gating is considered to importantly
      contribute to core schizophrenia symptoms such as psychotic disorganization and
      thought disturbance. We selected three candidate nNOS polymorphisms (Ex1f-VNTR,
      rs6490121 and rs41279104), associated with schizophrenia and cognition in
      previous studies, and tested their association with the efficiency of
      sensorimotor gating in healthy human adults. We found that risk variants of Ex1f
      VNTR and rs6490121 (but not rs41279104) were associated with a weaker prepulse
      inhibition (PPI) of the acoustic startle reflex, a standard measure of
      sensorimotor gating. Furthermore, the effect of presence of risk variants in Ex1f
      VNTR and rs6490121 was additive: PPI linearly decreased with increasing number of
      risk alleles, being highest in participants with no risk allele, while lowest in
      individuals who carry three risk alleles. Our findings indicate that NO is
      involved in the regulation of sensorimotor gating, and highlight one possible
      pathogenetic mechanism for NO playing a role in the development of schizophrenia
      psychosis.

PMID- 30096363
TI  - Roles of cohesin in chromosome architecture and gene expression.
AB  - Cohesin-mediated chromatin organization plays an important role in formation and
      stabilization of chromosome architecture and gene regulation. Mechanisms by which
      cohesin shapes chromosome and regulates gene expression remain unclear. The
      present article overviews biological characters and functions of cohesin and core
      subunits and explores roles of regulatory factors (e.g. Pds5, Wapl, and Eco1) in
      dynamic behaviors of cohesin. Cohesin interacts with CCCTC binding factor (CTCF)
      and other factors to maintain and stabilize multi-dimensional organizations of
      topological loops and distances between sites during cell segmentation. We also
      describe functional roles of cohesin in cell cycle by entrapping sister
      chromatids to form embrace and handcuff models, loading onto chromatin,
      establishing cohesion function, and regulating removal of cohesin and associated
      factors from the chromosome arm through prophase pathway or at onset of anaphase.
      It is questioned whether those factors associated with cohesin-regulated
      processes can be identified as biology- or disease-specific biomarkers and
      druggable targets to dynamically monitor changes during phasing, staging,
      progressing, and responding of diseases. It is also expected to explore
      heterogenetic roles of cohesin between single cells and regulatory roles of
      cohesin in trans-omic profiles and functions. Further understanding of cohesin
      functions will be beneficial to improve diagnosis and treatment of
      cohesinopathies.

PMID- 30096362
TI  - Bio-guided fractionation and isolation of active component from Tragopogon
      graminifolius based on its wound healing property.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Tragopogon graminifolius (T. graminifolius) from
      Asteraceae family has been used as a remedy in Persian traditional medicine for
      the treatment of various disorders such as wound healing. AIM OF THE STUDY: The
      purpose of this study is to investigate the compounds of T. graminifolius, which
      are responsible for its wound healing activity. MATERIALS AND METHODS: The
      experiment was performed in three phases; each phase consisted of fractionation
      of extracts followed by scratch assay. The results of the scratch assay were
      expressed using scratch closure index (SCI), representing the contraction of
      scratch. RESULTS: In phase I, Ethyl acetate fraction (E) showed the maximum SCI
      (61.7 +/- 3.5) that was selected for more fractionation in the next phase. In
      phase II, 12 fractions were obtained and labeled as fractions E- A to L,
      respectively. Based on the SCI of fractions, EF (SCI=68.9 +/- 0.6) was the most
      active fraction in phase II and selected for further fractionation in phase III.
      In phase III, 8 fractions were resulted by fractionation of EF and labeled as EF-
      1-8. Fraction EF5 with the highest SCI (30.8 +/- 3.0) was the most effective
      fraction and Luteolin was the main component. Luteolin significantly improved
      viability of fibroblast cells and increased cell population that was accompanied
      by decreased cell apoptosis. Luteolin-induced cell number increase in the S and
      G2M phases of the cell cycle, further confirms the proliferative effect of this
      compound. CONCLUSION: The results showed that the total extract and fractions of
      T. graminifolius stimulate proliferation and migration of skin fibroblast cells
      and Luteolin is one of the active compounds responsible for these effects.

PMID- 30096364
TI  - Roles of NIPBL in maintenance of genome stability.
AB  - A cohesin-loading factor (NIPBL) is one of important regulatory factors in the
      maintenance of 3D genome organization and function, by interacting with a large
      number of factors, e.g. cohesion, CCCTC-binding factor (CTCF) or cohesin complex
      component. The present article overviews the critical and regulatory roles of
      NIBPL in cohesion loading on chromotin and in gene expression and transcriptional
      signaling. We explore molecular mechanisms by which NIPBL recruits endogenous
      histone deacetylase (HDAC) to induce histone deacetylation and influence multi
      dimensions of genome, through which NIPBL "hop" movement in chromatin regulates
      gene expression and alters genome folding. NIPBL regulates the process of CTCF
      and cohesion into chromatin loops and topologically associated domains, binding
      of cohesion and H3K4mes3 through interaction among promoters and enhancers. HP1
      recruits NIPBL to DNA damage site through RNF8/RNF168 ubiquitylation pathway.
      NIPBL contributes to regulation of genome-controlled gene expression through the
      influence of cohesin in chromosome structure. NIPBL interacts with cohesin and
      then increases transcriptional activities of REC8 promoter, leading to up
      regulation of gene expression. NIPBL movement among chromosomal loops regulates
      gene expression through dynamic alterations of genome organization. Thus, we
      expect a new and deep insight to understand dynamics of chromosome and explore
      potential strategies of therapiesc on basis of NIPBL.

PMID- 30096365
TI  - One protein to rule them all: The role of CCCTC-binding factor in shaping human
      genome in health and disease.
AB  - The eukaryotic genome, constituting several billion base pairs, must be
      contracted to fit within the volume of a nucleus where the diameter is on the
      scale of MUm. The 3D structure and packing of such a long sequence cannot be left
      to pure chance, as DNA must be efficiently used for its primary roles as a matrix
      for transcription and replication. In recent years, methods like chromatin
      conformation capture (including 3C, 4C, Hi-C, ChIA-PET and Multi-ChIA) and
      optical microscopy have advanced substantially and have shed new light on how
      eukaryotic genomes are hierarchically organized; first into 10-nm fiber, next
      into DNA loops, topologically associated domains and finally into interphase or
      mitotic chromosomes. This knowledge has allowed us to revise our understanding
      regarding the mechanisms governing the process of DNA organization. Mounting
      experimental evidence suggests that the key element in the formation of loops is
      the binding of the CCCTC-binding factor (CTCF) to DNA; a protein that can be
      referred to as the chief organizer of the genome. However, CTCF does not work
      alone but in cooperation with other proteins, such as cohesin or Yin Yang 1
      (YY1). In this short review, we briefly describe our current understanding of the
      structure of eukaryotic genomes, how they are established and how the formation
      of DNA loops can influence gene expression. We discuss the recent discoveries
      describing the 3D structure of the CTCF-DNA complex and the role of CTCF in
      establishing genome structure. Finally, we briefly explain how various genetic
      disorders might arise as a consequence of mutations in the CTCF target sequence
      or alteration of genomic imprinting.

PMID- 30096366
TI  - The utility of HepaRG cells for bioenergetic investigation and detection of drug
      induced mitochondrial toxicity.
AB  - The importance of mitochondrial toxicity in drug-induced liver injury is well
      established. The bioenergetic phenotype of the HepaRG cell line was defined in
      order to assess their suitability as a model of mitochondrial hepatotoxicity.
      Bioenergetic phenotyping categorised the HepaRG cells as less metabolically
      active when measured beside the more energetic HepG2 cells. However, inhibition
      of mitochondrial ATP synthase induced an increase in glycolytic activity of both
      HepaRG and HepG2 cells suggesting an active Crabtree Effect in both cell lines.
      The suitability of HepaRG cells for the acute metabolic modification assay as a
      screen for mitotoxicity was confirmed using a panel of compounds, including both
      positive and negative mitotoxic compounds. Seahorse respirometry studies
      demonstrated that a statistically significant decrease in spare respiratory
      capacity is the first indication of mitochondrial dysfunction. Furthermore, based
      upon comparing changes in respiratory parameters to those of the positive
      controls, rotenone and carbonyl cyanide m-chlorophenyl hydrazone, compounds were
      categorised into two mechanistic groups; inhibitors or uncouplers of the electron
      transport chain. Overall, the findings from this study have demonstrated that
      HepaRG cells, despite having different resting bioenergetic phenotype to HepG2
      cells are a suitable model to detect drug-induced mitochondrial toxicity with
      similar detection rates to HepG2 cells.

PMID- 30096367
TI  - Application of the comparison approach to open TG-GATEs: A useful toxicogenomics
      tool for detecting modes of action in chemical risk assessment.
AB  - Mode of action information is one of the key components for chemical risk
      assessment as mechanistic insight leads to better understanding of potential
      adverse health effects of a chemical. This insight greatly facilitates assessment
      of human relevance and enhances the use of non-animal methods for risk
      assessment, as it ultimately enables extrapolation from initiating events to
      adverse effects. Recently, we reported an in vitro toxicogenomics comparison
      approach to categorize (non-)genotoxic carcinogens according to similarities in
      their proposed modes of action. The present study aimed to make this comparison
      approach generally applicable, allowing comparison of outcomes across different
      studies. The resulting further developed comparison approach was evaluated
      through application to toxicogenomics data on 18 liver toxicants in human and rat
      primary hepatocytes from the Open TG-GATEs database. The results showed sensible
      matches between compounds with (partial) overlap in mode of action, whilst
      matches for compounds with different modes of action were absent. Comparison of
      the results across species revealed pronounced and relevant differences between
      primary rat and human hepatocytes, underpinning that information on mode of
      action enhances assessment of human relevance. Thus, we demonstrate that the
      comparison approach now is generally applicable, facilitating its use as tool in
      mechanism-based risk assessment.

PMID- 30096368
TI  - Parsing a mental program: Fixation-related brain signatures of unitary operations
      and routines in natural visual search.
AB  - Visual search involves a sequence or routine of unitary operations (i.e.
      fixations) embedded in a larger mental global program. The process can indeed be
      seen as a program based on a while loop (while the target is not found), a
      conditional construct (whether the target is matched or not based on specific
      recognition algorithms) and a decision making step to determine the position of
      the next searched location based on existent evidence. Recent developments in our
      ability to co-register brain scalp potentials (EEG) during free eye movements has
      allowed investigating brain responses related to fixations (fixation-Related
      Potentials; fERPs), including the identification of sensory and cognitive local
      EEG components linked to individual fixations. However, the way in which the
      mental program guiding the search unfolds has not yet been investigated. We
      performed an EEG and eye tracking co-registration experiment in which
      participants searched for a target face in natural images of crowds. Here we show
      how unitary steps of the program are encoded by specific local target detection
      signatures and how the positioning of each unitary operation within the global
      search program can be pinpointed by changes in the EEG signal amplitude as well
      as the signal power in different frequency bands. By simultaneously studying
      brain signatures of unitary operations and those occurring during the sequence of
      fixations, our study sheds light into how local and global properties are
      combined in implementing visual routines in natural tasks.

PMID- 30096369
TI  - Speeded response errors and the error-related negativity modulate early sensory
      processing.
AB  - Empirical research demonstrates that when the time following error commission is
      constrained, subsequent sensory processing can be impaired (Buzzell et al.,
      2017). This reduction in sensory processing is presumably due to a bottleneck for
      cognitive resources produced by an overlap between error processing and
      subsequent stimulus processing. This finding suggests that the system dedicated
      to improving task performance can actually sometimes be the source of performance
      failures. Although this finding established that data-limited errors lead to a
      reduction in sensory processing at short response stimulus intervals (RSIs), it
      remains unclear if the relationship between error processing and subsequent
      sensory processing can be modulated by speeded-response errors. In the present
      study, event-related potentials and behavioral measures were recorded while
      participants performed a modified version of a Simon task, in which RSI duration
      was varied. We found that sensory processing, indexed by the P1 component, was
      reduced following errors at short (200-533 ms), but not long (866-1200 ms), RSIs.
      Moreover, the magnitude of error processing differentially influenced subsequent
      sensory processing as a function of RSI. However, whereas prior work demonstrated
      that the error positivity (Pe) modulated sensory processing on the subsequent
      trial, only the error-related negativity (ERN) did so within the Simon task. This
      suggests that although both data-limited errors and speeded-response errors can
      impact subsequent sensory processing, different stages of error processing appear
      to mediate this phenomenon.

PMID- 30096370
TI  - Genome-based deletion analysis in Aspergillus terreus reveals the acetylaranotin
      bis-thiomethyltransferase gene.
AB  - Acetylaranotin is an epipolythiodiketopiperazine (ETP) secondary metabolite with
      a broad range of bioactivities. We demonstrated that ATEG_01465.1 located outside
      of acetylaranotin gene cluster is responsible for catalyzing the S-methylation of
      its biosynthetic pathway. Combining the previous characterization of
      acetylaranotin biosynthetic gene cluster together with the identification of its
      S-methyltransferase provides a means to obtain second-generation acetylaranotin
      derivatives previously inaccessible. By permutations of targeted deletions of
      ATEG_01465.1, acetyltransferase (AtaH), and benzoate hydroxylase (AtaY), three
      novel acetylaranotin derivatives were produced by Aspergillus terreus.

PMID- 30096371
TI  - Effect of a C-end rule modification on antitumor activity of thymosin alpha1.
AB  - Thymosin alpha1 (Talpha1), a hormone containing 28 amino acids, has been approved
      in several cancer therapies, but the lack of tumor-targeting hinders its full use
      in tumor treatment. We designed a new peptide by connecting Talpha1 and RGDR,
      generating a product, Talpha1-RGDR, where RGDR is located in the C-end with both
      tumor-homing and cell internalizing properties (C-end rule peptides, a consensus
      R/KXXR/K motif). This work aimed to study the antitumor and immunological
      activities of Talpha1-RGDR, and its differences compared with the wild-type
      Talpha1. The antitumor and immunological activities of Talpha1-RGDR were measured
      using the B16F10 tumor and immunologic suppression models. Talpha1-RGDR treatment
      led to significant inhibition of tumor growth at a dose at which Talpha1 showed a
      slight effect in the B16F10 tumor growth model. In the immunologic suppression
      model, Talpha1-RGDR shared almost equivalent immunomodulatory effect with
      Talpha1. These results demonstrated the better therapeutic effects after
      treatment with Talpha1-RGDR compared with Talpha1. Moreover, both Talpha1-RGDR
      and Talpha1 shared a helical conformation in the presence of trifluoroethanol
      based on CD spectroscopy. Our dock information of Talpha1-RGDR when combined with
      integrin alphavbeta3 or neuropilin-1 further confirmed previous experimental
      results. All these findings suggest that Talpha1-RGDR might be a useful therapy
      for tumors by overcoming its wild type limitation of tumor homing.

PMID- 30096372
TI  - Irradiation by gamma-rays reduces the level of H3S10 phosphorylation and weakens
      the G2 phase-dependent interaction between H3S10 phosphorylation and gammaH2AX.
AB  - Histone posttranslational modifications regulate diverse nuclear functions,
      including DNA repair. Here, we use mass spectrometry, western blotting,
      immunohistochemistry and advanced confocal microscopy in order to show radiation
      specific changes in the histone signature. We studied wild-type mouse embryonic
      stem cells (mESCs) and mESCs with a depletion of histone deacetylase 1 (HDAC1),
      which plays a role in DNA repair. Irradiation by gamma-rays increased the S139
      phosphorylation of histone H2AX but reduced the level of the H3K9-R17 peptide,
      which contains S10 phosphorylation (H3S10ph). On an individual cellular level,
      H3S10ph was low in highly gammaH2AX-positive UV laser-induced DNA lesions, and
      this nuclear distribution pattern was not changed by HDAC1 depletion. Despite
      this fact, spontaneous gammaH2AX-positive DNA lesions colocalized with large
      H3S10ph-positive nuclear bodies that appear in the G2 phase of the cell cycle.
      Similarly, by FLIM-FRET analysis, we observed an interaction between H3S10ph and
      gammaH2AX in the G2 phase. However, this interaction was reduced when cells were
      exposed to gamma-rays. A mutual link between H3S10ph and gammaH2AX was not
      observed in the G1 phase of the cell cycle. Together, our data show that despite
      the fact that H3S10ph is not directly involved in DNA repair, a decrease in H3S10
      phosphorylation and weakened interaction between H3S10ph and gammaH2AX is a
      result of radiation-induced damage of the genome. In this case, gamma-irradiation
      also decreased the number of cells in the G1 phase, characterized by no
      interaction between H3S10ph and gammaH2AX.

PMID- 30096373
TI  - A novel recombinant human Frizzled-7 protein exhibits anti-tumor activity against
      triple negative breast cancer via abating Wnt/beta-catenin pathway.
AB  - Triple negative breast cancer (TNBC) is one of the most difficult malignancy to
      treat due to a lack of targeted therapy. Studies have demonstrated that the
      activation of Wnt/beta-catenin signaling was preferentially found in TNBC.
      Frizzled-7 (Fzd7), one of the Wnt receptors, was significantly up-regulated in
      TNBC and modulated TNBC tumorigenesis through the Wnt signaling pathway,
      indicating Fzd7 is a biomarker and a potential therapeutic target for TNBC. Here,
      we designed a recombinant soluble peptide fragment (rhFzd7) to antagonize Fzd7 by
      competitively binding with Wnt ligands. We demonstrated the ability of rhFzd7 to
      bind to its ligand, Wnt3a, and monitored the kinetic process using a Biacore X100
      system. In addition, the anti-tumor and anti-angiogenic activity of rhFzd7 were
      studied in vitro and in vivo. Results showed that the purified rhFzd7 pulled down
      Wnt3a from MDA-MB-231 cells and exhibited high affinity with Wnt3a (KD: 3.41 * 10
      8 M). The data in vitro revealed that rhFzd7 inhibited proliferation and invasion
      of TNBC cells, and induced apoptosis of TNBC cells effectively. The anti
      angiogenic assay indicated that rhFzd7 repressed TNBC angiogenesis in vitro and
      in vivo. Furthermore, the study in vivo showed that rhFzd7 could sensitize TNBC
      cells to the anti-tumor effect of Docetaxel. In conclusion, the generation of
      rhFzd7 lays foundation for the screening of anti-Fzd7 antibody, and this novel
      design provides an effective candidate for the clinical treatment of TNBC.

PMID- 30096375
TI  - Astrogliopathology in the infectious insults of the brain.
AB  - Astroglia, a heterogeneous type of neuroglia, play key homeostatic functions in
      the central nervous system (CNS) and represent an important defence system.
      Impaired homeostatic capacity of astrocytes manifests in diseases and this is
      mirrored in various astrocyte-based pathological features including reactive
      astrogliosis, astrodegeneration with astroglial atrophy and pathological
      remodelling of astrocytes. All of these manifestations are most prominently
      associated with infectious insults, mediated by bacteria, protozoa and viruses.
      Here we focus onto neurotropic viruses such as tick-borne encephalitis (TBEV) and
      Zika virus (ZIKV), both belonging to Flaviviridae and both causing severe
      neurological impairments. We argue that astrocytes provide a route through which
      neurotropic infectious agents attack the CNS, since they are anatomically
      associated with the blood-brain barrier and exhibit aerobic glycolysis, a
      metabolic specialisation of highly morphologically dynamic cells, which may
      provide a suitable metabolic milieu for proliferation of infectious agents,
      including viral bodies.

PMID- 30096374
TI  - Lipemia retinalis as the presenting sign of undiagnosed type 1 diabetes mellitus
      resulting in severe secondary hypertriglyceridemia.
AB  - We describe the clinical course of an 11-year-old girl diagnosed with lipemia
      retinalis as the presenting sign of diabetes mellitus type 1 with severe
      secondary hypertriglyceridemia. By performing serial multimodal imaging studies,
      we provide a comprehensive description of the clinical manifestations associated
      with severe hypertriglyceridemia to promote recognition of this rare clinical
      diagnosis.

PMID- 30096376
TI  - Reply to: Assessment of 'neural respiratory drive' from the parasternal
      intercostal muscles.

PMID- 30096377
TI  - Management of vertebral fragility fractures: a clinical care pathway developed by
      a multispecialty panel using the RAND/UCLA Appropriateness Method.
AB  - BACKGROUND CONTEXT: Vertebral fragility fractures (VFFs), mostly due to
      osteoporosis, are very common and are associated with significant morbidity and
      mortality. There is a lack of consensus on the appropriate management of patients
      with or suspected of having a VFF. PURPOSE: This work aimed at developing a
      comprehensive clinical care pathway (CCP) for VFF. STUDY DESIGN/SETTING: The
      RAND/UCLA Appropriateness Method was used to develop patient-specific
      recommendations for the various components of the CCP. The study included two
      individual rating rounds and two plenary discussion sessions. METHODS: A
      multispecialty expert panel (orthopedic and neurosurgeons, interventional
      [neuro]radiologists and pain specialists) assessed the importance of 20 signs and
      symptoms for the suspicion of VFF, the relevance of 5 diagnostic procedures, the
      appropriateness of vertebral augmentation versus nonsurgical management for 576
      clinical scenarios, and the adequacy of 6 aspects of follow-up care. RESULTS: The
      panel identified 10 signs and symptoms believed to be relatively specific for
      VFF. In patients suspected of VFF, advanced imaging was considered highly
      desirable, with MRI being the preferred diagnostic modality. Vertebral
      augmentation was considered appropriate in patients with positive findings on
      advanced imaging and in whom symptoms had worsened and in patients with 2 to 4
      unfavorable conditions (eg, progression of height loss and severe impact on
      functioning), dependent on their relative weight. Time since fracture was
      considered less relevant for treatment choice. Follow-up should include
      evaluation of bone mineral density and treatment of osteoporosis. CONCLUSIONS:
      Using the RAND/UCLA Appropriateness Method, a multispecialty expert panel
      established a comprehensive CCP for the management of VFF. The CCP may be helpful
      to support decision-making in daily clinical practice and to improve quality of
      care.

PMID- 30096378
TI  - Cardiac-Sparing Whole Lung Intensity Modulated Radiation Therapy in Children with
      Wilms Tumor: Final Report on Technique and Abdominal Field Matching to Maximize
      Normal Tissue Protection.
AB  - PURPOSE: Cardiac-sparing whole lung intensity modulated radiation therapy (WL
      IMRT) has been shown to improve cardiac protection and lung volume dose coverage
      compared with standard anteroposterior techniques. This dosimetry study had 2
      aims: To determine the dosimetric advantages of a modified WL IMRT (M-WL IMRT)
      technique, designed to reduce radiation exposure to the thyroid gland and breast
      tissues, compared with standard WL IMRT (S-WL IMRT) and to determine the
      dosimetric advantages of M-WL IMRT and dosimetrically matched abdomen and flank
      radiation therapy (RT) fields designed to reduce normal tissue exposure compared
      with standard field matching techniques. METHODS AND MATERIALS: Computed
      tomography scans of the chest and abdomen that were obtained during computed
      tomography simulation of 10 female children were used. For Aim 1, for S-WL IMRT,
      the planning target volume (PTV) was obtained with a 1-cm expansion of the 4
      dimensional lung volume (internal target volume). For M-WL IMRT, the PTV was
      reduced around the breast and thyroid gland to facilitate thyroid and breast
      sparing. For Aim 2, standard matching techniques for 3-dimensional
      anterior/posterior-posterior/anteriorwhole lung and abdominal RT fields were
      compared with a new dosimetric matching technique for WL IMRT and abdomen and
      flank fields. For both aims, the dose coverage of the lungs and radiation
      exposure to normal tissues (heart, thyroid, breasts) were statistically compared.
      RESULTS: Compared with S-WL IMRT, the M-WL IMRT technique provided similar lung
      PTV dose coverage and a significantly superior reduction in mean breast and
      thyroid doses, without compromising cardiac protection. The M-WL IMRT technique
      combined with a dosimetrically matched abdomen and flank fields showed
      significantly superior normal tissue protection compared with standard matched
      anterior/posterior-posterior/anteriorlung and abdomen and flank RT fields.
      CONCLUSIONS: This study has shown that the M-WL IMRT technique can reduce
      radiation exposure to the thyroid gland and breast tissue without compromising
      cardiac protection and 4-dimensional lung volume dose coverage. This report also
      describes a new dosimetric matching technique between WL IMRT and abdomen and
      flank fields that will improve normal tissue sparing compared with standard
      techniques.

PMID- 30096379
TI  - Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy.
AB  - PURPOSE: This study aimed to investigate 3 planning target volume (PTV) margin
      expansions and determine the most appropriate volume to be used in bladder
      preservation therapy when using daily cone beam computed tomography (CBCT). We
      aimed to establish whether a smaller PTV expansion is feasible without risking
      geographical miss. METHODS AND MATERIALS: The study included patients with
      bladder cancer who were treated with a hypofractionated course of radiation
      therapy delivered with intensity modulated radiation therapy. The clinical target
      volume (CTV) was the whole empty bladder, and the PTV consisted of a 1.5-cm
      margin around the bladder (PTV1.5 cm). Patients underwent daily CBCT imaging
      before treatment to assess the bladder volume and ensure accurate positioning. We
      investigated 2 additional smaller PTV margin expansions to determine the most
      appropriate volume to be used with CBCT as a daily image guided radiation therapy
      modality. These margins were created retrospectively on every CBCT. The first
      additional volume was a uniform PTV margin of the surrounding 1 cm (PTV1 cm).
      When considering that the majority of the internal bladder movement was due to
      the variation in filling that occurs in the superior and anterior directions, a
      second volume of an anisotropic PTV margin with a 1.5-cm superior/anterior and 1
      cm in other directions (PTV1/1.5 cm) was created. We recorded the frequency and
      measured the volume of bladder falling out of each PTV based on the daily CBCT.
      RESULTS: For the purpose of this study, we considered an arbitrary 5 cm3 of CTV
      falling out of the designated PTV as a clinically significant volumetric miss.
      The frequency of such a miss when applying the uniform PTV1 cm was 1%. However,
      when applying the uniform PTV1.5 cm and anisotropic PTV1/1.5 cm margins, the
      frequency was 0.5% and 0.5%, respectively. CONCLUSIONS: The anisotropic PTV
      expansion of 1.5 cm superiorly and anteriorly and 1 cm in all other directions
      around the bladder (CTV) provides a safe PTV approach when daily CBCT imaging is
      used to localize an empty bladder.

PMID- 30096380
TI  - Fluorine-18 labeled diphenyl sulfide derivatives for imaging serotonin
      transporter (SERT) in the brain.
AB  - OBJECTIVES: Serotonin transporters (SERT) play an important role in controlling
      serotonin concentration in the synaptic cleft and in managing postsynaptic signal
      transduction. Inhibitors of SERT binding are well known as selective serotonin
      reuptake inhibitors (SSRIs) such as fluoxetine, sertraline, paroxetine, and
      escitalopram, that are commonly prescribed antidepressants. Positron emission
      tomography (PET) and single photon emission tomography (SPECT) imaging agents
      targeting SERT may be useful for studying its function and providing a tool for
      monitoring drug treatment. METHODS: A series of novel 18F-labeled diphenyl
      sulfide derivatives were prepared and tested for their binding affinity. Among
      them, 2-((2-((dimethylamino)-methyl)-4-(2-(2
      fluoroethoxy)ethoxy)phenyl)thio)aniline, 1, which showed excellent binding toward
      serotonin transporter (SERT) in the brain (Ki = 0.09 nM), was selected for
      further evaluation. An active OTs intermediate, 7, was treated with [18F]F-/K222
      to provide [18F]1 in one step and in high radiochemical yields. This new SERT
      targeting agent was evaluated in rats by biodistribution studies and animal PET
      imaging studies. RESULTS: The radiolabeling reaction led to the desired [18F]1.
      After HPLC purification no-carrier-added [18F]1 was obtained (radiochemical
      yield, 23-47% (n = 10,); radiochemical purity >99%; molar activity, 15-28
      GBq/MUmol). Biodistribution studies with [18F]1 showed good brain uptake (1.04%
      dose/g at 2 min post-injection), high uptake into the hypothalamus (1.55% dose/g
      at 30 min), and a high target-to-non-target (hypothalamus to cerebellum) ratio of
      6.1 at 120 min post-injection. A PET imaging study in normal rats showed
      excellent uptake in the midbrain and thalamus regions known to be rich in SERT
      binding sites at 60 min after iv injection. Chasing experiment with escitalopram
      (iv, 2 mg/kg) in a rat at 60 min after iv injection caused a noticeable reduction
      in the regional radioactivity and the target-to-non-target ratio, suggesting
      binding by [18F]1 was highly specific and reversible for SERT binding sites in
      the brain. CONCLUSIONS: A novel diphenyl sulfide derivative, [18F]1 for SERT
      imaging was successfully prepared and evaluated. Results suggest that this new
      chemical entity is targeting SERT binding sites in the brain, and it is a
      suitable candidate for future commercial development.

PMID- 30096382
TI  - High-Throughput Copy Number Profiling by Digital Multiplex Ligation-Dependent
      Probe Amplification in Multiple Myeloma.
AB  - Multiple myeloma (MM) is a genetically heterogeneous disease with a diverse
      clinical outcome. Copy number alterations (CNAs), including whole chromosome and
      subchromosomal gains and losses, are common contributors of the pathogenesis and
      have demonstrated prognostic impact in MM. We tested the performance of digital
      multiplex ligation-dependent probe amplification (digitalMLPA), a novel technique
      combining MLPA and next-generation sequencing, to detect disease-related CNAs.
      Copy number status at 371 genomic loci was simultaneously analyzed in 56
      diagnostic bone marrow samples, which were also examined by conventional MLPA and
      interphase fluorescence in situ hybridization (iFISH). On average, digitalMLPA
      identified 4.4 subchromosomal CNAs per patient. The increased number of probes
      compared with conventional MLPA allowed a detailed mapping of CNAs, especially on
      chromosome 1, where 24 different patterns were observed in 38 patients harboring
      loss(1p) and/or gain(1q). iFISH, MLPA, and digitalMLPA results at loci
      investigated by multiple methods showed a congruency of 95%. Besides precise
      characterization of hyperdiploid karyotypes not efficiently achievable by iFISH
      or MLPA, digitalMLPA unraveled 156 CNAs not detected by the other two methods in
      45 patients (80%). In addition, we provide proof of principle that digitalMLPA
      can detect known point mutations, in this case the BRAFV600E. Our study
      demonstrates the robustness of digitalMLPA to profile CNAs and to screen point
      mutations in MM, which could efficiently be used in myeloma diagnostics.

PMID- 30096383
TI  - Recent milestone U.S. ophthalmic product approvals and clearances.

PMID- 30096384
TI  - Gut inflammation exacerbates hepatic injury in the high-fat diet induced NAFLD
      mouse: Attention to the gut-vascular barrier dysfunction.
AB  - AIMS: Gut inflammation has been put forward to be associated with hepatic injury
      in the clinical practice. The dismantled intestinal barrier was highly concerned,
      however, largely unknown about the role of gut-vascular barrier (GVB) in this
      process. This study aimed to investigate if inflamed gut directly contributes to
      the progression of non-alcoholic steatohepatitis (NASH), especially attention to
      the GVB dysfunction. MAIN METHODS: Male C57bl/6 mice were fed with a high-fat
      diet (HFD) and 1% DSS for 12 weeks. The colonic inflammatory injury as well as
      hepatic injury were evaluated. The GVB function was assessed via measuring the
      permeability to fluorescently-labeled dextran (70 kDa) and the expression of
      plasmalemma vesicle-associated protein-1 (PV1). Furthermore, the plasma endotoxin
      level and hepatic TLR4/TLR9 mRNA expression were detected. KEY FINDINGS: There
      were evident colitis in DSS-exposed mice, which trend to be more apparent in HFD
      ones. The HFD + DSS mice exhibited more serious hepatic steatosis, inflammation
      and fibrosis than HFD groups. The downregulated tight junction protein in HFD +
      DSS mice indicated loss of epithelial barrier. The GVB disruption were also
      confirmed with increased permeability to macromolecules and high expression of
      endothelial PV1 in HFD + DSS mice. Accordingly, potentially elevated plasma
      endotoxin levels and markedly increased TLR4/TLR9 mRNA expression were
      demonstrated in HFD + DSS mice rather than HFD groups. SIGNIFICANCE: Gut
      inflammation exacerbates liver injury and fibrosis in HFD mice, which may
      contribute to the development of NASH. Beyond the damaged intestinal epithelial
      barrier, GVB disruption with bacterial translocation into may play a key role in
      the pathogenesis of NASH.

PMID- 30096381
TI  - Curating Clinically Relevant Transcripts for the Interpretation of Sequence
      Variants.
AB  - Variant interpretation depends on accurate annotations using biologically
      relevant transcripts. We have developed a systematic strategy for designating
      primary transcripts and have applied it to 109 hearing loss-associated genes that
      were divided into three categories. Category 1 genes (n = 38) had a single
      transcript; category 2 genes (n = 33) had multiple transcripts, but a single
      transcript was sufficient to represent all exons; and category 3 genes (n = 38)
      had multiple transcripts with unique exons. Transcripts were curated with respect
      to gene expression reported in the literature and the Genotype-Tissue Expression
      Project. In addition, high-frequency loss-of-function variants in the Genome
      Aggregation Database and disease-causing variants in ClinVar and the Human Gene
      Mutation Database across the 109 genes were queried. These data were used to
      classify exons as clinically significant, insignificant, or of uncertain
      significance. Interestingly, 6% of all exons, containing 124 reportedly disease
      causing variants, were of uncertain significance. Finally, we used exon-level
      next-generation sequencing quality metrics generated at two clinical laboratories
      and identified a total of 43 technically challenging exons in 20 different genes
      that had inadequate coverage and/or homology issues that might lead to false
      variant calls. We have demonstrated that transcript analysis plays a critical
      role in accurate clinical variant interpretation.

PMID- 30096385
TI  - The effect of blood flow restriction along with low-intensity exercise on cardiac
      structure and function in aging rat: Role of angiogenesis.
AB  - AIMS: Low-intensity aerobic training along with limbs blood flow restriction can
      improve mass and strength of skeletal muscle, but its effects on aging heart
      structure and performance is unidentified. We investigated the effects of this
      model of training on myocardial function, histology and angiogenesis in old male
      rats. MAIN METHODS: Animals randomly were divided into control (Ctl), sham
      operated (Sh), limbs blood flow restriction (BFR), sham-operated plus 10 weeks
      low intensity treadmill exercise (Sh + Ex), and BFR plus exercise (BFR + Ex)
      groups. Finally, blood pressure, heart physiological and stereological
      parameters, myocardial oxygen consumption index and expression of vascular
      endothelial growth factor (VEGF) and its receptors (Flt-1 and kdr) were assessed.
      KEY FINDINGS: BFR + Ex group had significantly lower heart rate (P < 0.05 vs. Ctl
      and Sh groups), rate-pressure product (RPP) and left ventricular end diastolic
      pressure (P < 0.05 and P < 0.01 vs. untrained groups, respectively). BFR + Ex
      group also had greater +dp/dt max (P < 0.01) and -dp/dt max (P < 0.05) than
      untrained groups. A significant increase in volumes of left ventricle and
      myocytes (P < 0.05, vs. Ctl and Sham), ventricular hypertrophy index and
      capillaries length density (P < 0.05 vs. untrained groups) were observed in BFR +
      Ex group. The level of VEGF and Flt-1 proteins and their mRNAs increased in the
      BFR + Ex group compared to Ctl, Sh and BFR (P < 0.01) and Sh + Ex (P < 0.05)
      groups. The kdr mRNA and its protein level were significantly higher in the BFR +
      Ex group. SIGNIFICANCE: Findings suggest that BFR plus exercise through improving
      the angiogenesis, physiological cardiac remodeling and oxygen demand/supply
      matching can promote cardiac performance in the elderly rats.

PMID- 30096388
TI  - Rural and urban food allergy prevalence from the South African Food Allergy
      (SAFFA) study.
AB  - BACKGROUND: Food sensitization and challenge-proved food allergy (FA) have not
      been compared in urban and rural settings. OBJECTIVE: We sought to determine and
      compare the prevalence of food sensitization and challenge-proved IgE-mediated FA
      in urban and rural South African toddlers aged 12 to 36 months. METHODS: This
      cross-sectional study of unselected children included 1185 participants in urban
      Cape Town and 398 in the rural Eastern Cape. All participants completed a
      questionnaire and underwent skin prick tests (SPTs) to egg, peanut, cow's milk,
      fish, soya, wheat, and hazelnut. Participants with SPT responses of 1 mm or
      greater to 1 or more foods and not tolerant on history underwent an open oral
      food challenge. RESULT: The prevalence of FA was 2.5% (95% CI, 1.6% to 3.3%) in
      urban children, most commonly to raw egg white (1.9%), followed by cooked egg
      (0.8%), peanut (0.8%), cow's milk (0.1%), and fish (0.1%). Urban sensitization
      (SPT response >=1 mm) to any food was 11.4% (95% CI, 9.6% to 13.3%) and 9.0% (95%
      CI, 7.5% to 10.8%) at an SPT response of 3 mm or greater. Sensitization in rural
      cohorts was significantly lower than in the urban cohort (1-mm SPT response, 4.5%
      [95% CI, 2.5% to 6.6%]; 3-mm SPT response, 2.8% [95% CI, 1.4% to 4.9%]; P < .01).
      In the rural black African cohort 0.5% (95% CI, 0.1% to 1.8%) of children had
      food allergy, all to egg. This is significantly lower than the prevalence of the
      urban cohort overall (2.5%) and urban black African participants (2.9%; 95% CI,
      1.5% to 4.3%; P = .006). CONCLUSION: FA prevalence in Cape Town is comparable
      with rates in industrialized middle-income countries and is significantly greater
      than in rural areas. Further analysis will describe and compare environmental
      exposures and other risk factors in this cohort.

PMID- 30096386
TI  - Co-administration with simvastatin or lovastatin alters the pharmacokinetic
      profile of sinomenine in rats through cytochrome P450-mediated pathways.
AB  - AIMS: Sinomenine, an anti-rheumatoid arthritis drug used in China for decades, is
      usually co-administered with cardiovascular (CV) drugs to reduce arthritis
      related risk of cardiovascular diseases. This study was to investigate whether
      and how CV drugs affect the pharmacokinetic profile of sinomenine. MAIN METHODS:
      In rat liver microsomes (RLMs), the key metabolic enzymes of sinomenine were
      identified by using specific inhibitors. The influences of CV drugs, including
      propranolol, verapamil, warfarin, atorvastatin, simvastatin, and lovastatin, on
      the metabolism of sinomenine were examined. Cocktail probe, RT-qPCR, and western
      blotting were performed to unveil the underlying mechanism of the drug-drug
      interaction. KEY FINDINGS: The key metabolic enzymes of sinomenine were
      identified to be CYP3A1/2 and CYP2D1 in RLMs. Among the CV drugs screened,
      simvastatin and lovastatin were shown to inhibit the liver metabolism of
      sinomenine with Ki values of 13.00 and 25.83 MUM, respectively. Single
      administration of simvastatin or lovastatin in rats increased the AUC value of
      sinomenine to 1.40- or 1.50-fold, and decreased the CLz/F value to 68.19% or
      65.44%, respectively. In contrast, multiple administrations of simvastatin, but
      not lovastatin, increased the CLz/F value of sinomenine to 1.38-fold and
      decreased the AUC value to 71.59%. Further studies showed that the long-term
      administration of simvastatin could up-regulate the expression of CYP3A1/2 to
      account for the effect. SIGNIFICANCE: This study demonstrated the potential
      effect of simvastatin and lovastatin on the metabolism of sinomenine for the
      first time. The findings provide guidelines for the co-administration of
      sinomenine with simvastatin or lovastatin in clinic.

PMID- 30096389
TI  - Tertiary lymphoid organs: A novel target in patients with chronic rhinosinusitis.

PMID- 30096387
TI  - A novel anti-osteoporotic agent that protects against postmenopausal bone loss by
      regulating bone formation and bone resorption.
AB  - AIMS: Postmenopausal osteoporosis is a bone metabolism disease that is caused by
      an imbalance between bone-resorbing osteoclast and bone-forming osteoblast
      actions. Herein, we describe the role of troxerutin (TRX), a trihydroxyethylated
      derivative of rutin, in ovariectomy (OVX)-induced osteoporosis and its effects on
      the regulation of osteoclasts and osteoblasts. MAIN METHODS: In vivo, OVX female
      mice were intraperitoneally injected with either saline, 50 mg/kg TRX, or 150
      mg/kg TRX for 6 weeks and then sacrificed for micro-computed tomography analyses,
      histological analyses, and biomechanical testing. In vitro, RAW264.7 cell-derived
      osteoclasts and MC3T3-E1 cell-derived osteoblasts were treated with different
      concentrations of TRX to examine the effect of TRX on osteoclastogenesis and bone
      resorption, as well as on osteogenesis and mineralization. KEY FINDINGS: In this
      study, we demonstrated that TRX prevented cortical and trabecular bone loss in
      ovariectomized mice by reducing osteoclastogenesis and promoting osteogenesis in
      vivo. In vitro, TRX inhibited the formation and activity of RAW264.7-derived
      osteoclasts and the expression of nuclear factor of activated T-cells 1 and
      cathepsin K. Meanwhile, TRX improved the osteogenesis and mineralization of MC3T3
      E1 by enhancing the expression of Runt-related transcription factor 2, Osterix,
      and collagen type 1 alpha 1. SIGNIFICANCE: Our data demonstrated that TRX could
      prevent OVX-induced osteoporosis and be used in a novel treatment for
      postmenopausal osteoporosis.

PMID- 30096390
TI  - Education-dependent activation of glycolysis promotes the cytolytic potency of
      licensed human natural killer cells.
AB  - BACKGROUND: The mechanism by which natural killer (NK) cell education results in
      licensed NK cells with heightened effector function against missing self-targets
      is not known. OBJECTIVE: We sought to identify potential mechanisms of enhanced
      function in licensed human NK cells. METHODS: We used expanded human NK cells
      from killer immunoglobulin-like receptor (KIR)/HLA-genotyped donors sorted for
      single-KIR+ cells to generate pure populations of licensed and unlicensed NK
      cells. We performed proteomic and gene expression analysis of these cells before
      and after receptor cross-linking and performed functional and metabolic analysis
      before and after interference with selected metabolic pathways. We verified key
      findings using freshly isolated and sorted NK cells from peripheral blood.
      RESULTS: We confirmed that licensed human NK cells are greater in number in
      peripheral blood and proliferate more in vitro than unlicensed NK cells. Using
      high-throughput protein analysis, we found that unstimulated licensed NK cells
      have increased expression of the glycolytic enzyme pyruvate kinase muscle isozyme
      M2 and after KIR cross-linking have increased phosphorylation of the metabolic
      modulators p38-alpha and 5' adenosine monophosphate-activated protein kinase
      alpha. After cytokine expansion and activation, unlicensed NK cells depended
      solely on mitochondrial respiration for cytolytic function, whereas licensed NK
      cells demonstrated metabolic reprogramming toward glycolysis and mitochondrial
      dependent glutaminolysis, leading to accumulation of glycolytic metabolites and
      depletion of glutamate. As such, blocking both glycolysis and mitochondrial
      dependent respiration was required to suppress the cytotoxicity of licensed NK
      cells. CONCLUSIONS: Collectively, our data support an arming model of education
      in which enhanced glycolysis in licensed NK cells supports proliferative and
      cytotoxic capacity.

PMID- 30096391
TI  - B lymphocyte-induced maturation protein 1 controls TH9 cell development, IL-9
      production, and allergic inflammation.
AB  - BACKGROUND: The transcriptional repressor B lymphocyte-induced maturation protein
      1 (Blimp-1) has a key role in terminal differentiation in various T-cell
      subtypes. However, whether Blimp-1 regulates TH9 differentiation and its role in
      allergic inflammation are unknown. OBJECTIVE: We aimed to investigate the role of
      Blimp-1 in TH9 differentiation and in the pathogenesis of allergic airway
      inflammation. METHODS: In vitro TH9 differentiation, flow cytometry, ELISA, and
      real-time PCR were used to investigate the effects of Blimp-1 on TH9
      polarization. T cell-specific Blimp-1-deficient mice, a model of allergic airway
      inflammation, and T-cell adoptive transfer to recombination-activating gene 1
      (Rag-1)-/- mice were used to address the role of Blimp-1 in the pathogenesis of
      allergic inflammation. RESULTS: We found that Blimp-1 regulates TH9
      differentiation because deleting Blimp-1 increased IL-9 production in CD4+ T
      cells in vitro. In addition, we showed that in T cell-specific Blimp-1-deficient
      mice, deletion of Blimp-1 in T cells worsened airway disease, and this worsening
      was inhibited by IL-9 neutralization. In asthmatic patients CD4+ T cells in
      response to TGF-beta plus IL-4 increased IL-9 expression and downregulated Blimp
      1 expression compared with expression in healthy control subjects. Blimp-1
      overexpression in human TH9 cells inhibited IL-9 expression. CONCLUSION: Blimp-1
      is a pivotal negative regulator of TH9 differentiation and controls allergic
      inflammation.

PMID- 30096392
TI  - Investigating innate immune mechanisms in early-life development and outcomes of
      food allergy.

PMID- 30096393
TI  - Improvement of kinetic properties and thermostability of recombinant Lepidium
      draba peroxidase (LDP) upon exposed to osmolytes.
AB  - In this study, effects of different concentrations of glycine and D-sorbitol were
      analyzed on the activity and thermostability of recombinant Lepidium draba
      peroxidase (LDP). Based on the results, activity of the enzyme increased in the
      presence of various concentrations of these osmolytes. Maximum activity was
      detected for the enzyme in the presence of 300 mM glycine and 600 mM sorbitol. In
      presence of the aforementioned doses of osmolytes, enzyme affinity for substrate
      (3,3',5,5'-tetramethylbenzidine and H2O2) and Vmax increased. According to the
      results, enzyme stability improved against temperature and H2O2. Furthermore,
      structural changes of the enzyme upon exposure to the osmolytes were revealed by
      the use of far-UV circular dichroism and fluorescence methods. The results
      showed, whereas the secondary structure of the enzyme was not significantly
      changed upon exposed to the osmolytes, the fluorescence studies revealed
      microenvironment of the aromatic residues dramatically affected by them. Overall,
      it may be speculated, structural changes of the enzyme upon exposed to the
      osmolytes, lead to the improvement of its kinetic properties and stability that
      can be benefit for using of it in in vitro applications.

PMID- 30096394
TI  - Preparation, characterization, antioxidant activity and protective effect against
      cellular oxidative stress of polysaccharide from Cynanchum auriculatum Royle ex
      Wight.
AB  - In the present study, a novel polysaccharide fraction (CAP2-1) from Cynanchum
      auriculatum Royle ex Wight was obtained by hot water extraction, ethanol
      precipitation and sequential purification through anion-exchange and size
      exclusion chromatography. CAP2-1 was a homogeneous heteropolysaccharide composed
      of mannose, rhamnose, glucuronic acid, galacturonic acid, galactose and
      arabinose, with an average molecular weight of 830.93 kDa. FT-IR and NMR spectra
      of CAP2-1 exhibited typical characteristic signals of polysaccharide. For
      antioxidant activity evaluation in vitro, CAP2-1 showed effective scavenging
      capacities against ABTS, DPPH and superoxide anion radical in a dose-dependent
      manner, with IC50 values at 0.1232, 0.5543 and 0.5881 mg/mL, respectively. At
      cellular level, CAP2-1 provided a significant protective effect against hydrogen
      peroxide-induced oxidative stress in HepG2 cells by a compositive oxidation
      defense mechanism. CAP2-1 could reduce oxidative stress by significantly
      enhancing the contents of antioxidant enzyme SOD and non-enzymatic antioxidant
      GSH in oxidative damaged cells, in addition to scavenging ROS directly and
      improving cell viability and membrane integrity, consequently achieving the
      intracellular antioxidant activity. The results unveiled that CAP2-1 could be
      explored as a promising natural antioxidant for application in functional foods.

PMID- 30096396
TI  - Pioglitazone inhibits advanced glycation induced protein modifications and down
      regulates expression of RAGE and NF-kappaB in renal cells.
AB  - The present work aims to determine the effect of pioglitazone on in-vitro albumin
      glycation and AGE-RAGE induced oxidative stress and inflammation. Bovine serum
      albumin was glycated by methylglyoxal in absence or presence of pioglitazone.
      Glycation markers (fructosamine, carbonyl groups, beta-amyloid aggregation, thiol
      groups, bilirubin binding capacity and AOPP); protein conformational changes
      (native-PAGE and HPLC analysis) were determined. Cellular study was done by
      estimating antioxidants, ROS levels, expression profile of membrane RAGE, NF
      kappaB and levels of inflammatory cytokines (IL-6, TNF-alpha) using HEK-293 cell
      line. We observed that levels of glycation markers were reduced at higher
      concentration of pioglitazone as compared to glycated albumin. Structural
      analysis of glycated albumin showed inhibition of protein migration and
      structural changes when treated with pioglitazone. Pioglitazone has potentially
      restored cellular antioxidants and reduced levels of IL-6 and TNF-alpha by
      declining expression of membrane RAGE and NF-kappaB. In conclusion, pioglitazone
      preferentially binds to protein and alleviates protein structural changes by
      maintaining its integrity. Additionally, it suppresses RAGE and NF-kappaB levels
      hence alleviate cellular oxidative stress and inflammation.

PMID- 30096395
TI  - Cloning and biochemical characterization of three glucose-6-phosphate
      dehydrogenase mutants presents in the Mexican population.
AB  - The deficiency of glucose-6-phosphate dehydrogenase (G6PD) is one of the most
      common inborn errors of metabolism worldwide. This congenital disorder generally
      results from mutations that are spread throughout the entire gene of G6PD. Three
      single-point mutations for G6PD have been reported in the Mexican population and
      named Veracruz (Arg365His), G6PD Seattle (Asp282His), and G6PD Mexico DF
      (Thr65Ala), whose biochemical characterization have not yet been studied. For
      this reason, in this work we analyzed the putative role of the three mutations to
      uncover the functional consequences on G6PD activity. To this end, was developed
      a method to clone, overexpress, and purify recombinant human G6PD. The results
      obtained from all variants showed a loss of catalysis by 80 to 97% and had a
      decrease in affinity for both physiological substrates with respect to the wild
      type (WT) G6PD. Our results also showed that the three mutations affected three
      dimensional structure and protein stability, suggesting an unstable structure
      with low conformational stability that affected its G6PD functionality. Finally,
      based on the biochemical characterization of the unclassified G6PD Mexico DF, we
      suggest that this variant could be grouped as a Class I variant, because
      biochemical data are similar with other Class I G6PDs.

PMID- 30096398
TI  - An in-depth view of potential dual effect of thymol in inhibiting xanthine
      oxidase activity: Electrochemical measurements in combination with four way
      PARAFAC analysis and molecular docking insights.
AB  - Xanthine oxidase (XO) can catalyze xanthine to uric acid and has also been linked
      with the extension of some serious diseases such as cancer, gout, diabetes and so
      on. Thymol is a part of diet in the form of spices. Due to the high antioxidant
      activity, its inhibitory effect on XO was studied in the present work. XO
      organized in four redox domains which exhibiting electrochemical signals.
      Therefore, voltammetric methods can be used to obtain the valuable information
      about the action mechanism of thymol on XO. However, there are extreme
      complexities in these biological sample matrices which make the deeper
      understanding of inhibition mechanism of thymol on XO activity is difficult.
      Thus, development of electrochemical techniques coupled with the four-way
      parallel factor analysis (PARAFAC) has provided promising solutions for analyzing
      of complex matrix. To better explore this inhibitory effect, electrochemical
      technologies have been used as a complement with ultraviolet and visible (UV-Vis)
      spectroscopy and molecular docking studies. For the first time, molecular docking
      studies were used to gain a fundamental understanding to explain how the electron
      transfer coupling occurs at XO active sites in the presence of thymol. It is in
      good agreement with the experimental data. These studies reveal that thymol could
      enter into the catalytic centers of XO. Also, it inhibits the XO activity through
      the direct binding to flavin adenine dinucleotides (FAD) center. The results
      display dose-dependent inhibition of XO with thymol. Its inhibitory activity was
      linked to its antioxidant properties to reduce the formation of free radicals
      (FRs) and related diseases.

PMID- 30096397
TI  - Molecular insights into the effect of ozone on human hemoglobin in
      autohemotherapy: Highlighting the importance of the presence of blood
      antioxidants during ozonation.
AB  - Ozone has been known for several decades, with its antiseptic and therapeutic
      effects determined by the hormesis theory. It is shown that the therapeutic
      efficacy of ozone therapy may be partly due to the controlled and moderate
      oxidative stress produced by the reaction of ozone with several biological
      components. In this study, the effect of ozone on healthy human hemoglobin (Hb)
      in the whole blood environment (in the presence of antioxidants) and in the
      purified form (in the absence of antioxidants) is investigated using a number of
      different techniques including intrinsic fluorescence, circular dichroism and UV
      VIS absorption spectroscopy as well as SDS- and Native-PAGE and dynamic light
      scattering. The results show that the presence of antioxidants prevents damage to
      Hb while its absence means that as the exposure to ozone is increased, Hb is
      increasingly damaged. These results highlight the importance for the use of
      appropriate doses of ozone, for patients with different diseases and hence
      antioxidant levels, in autohemotherapy.

PMID- 30096399
TI  - Enhanced thermostability of halo-tolerant glutaminase from Bacillus licheniformis
      ATCC 14580 by immobilization onto nano magnetic cellulose sheet and its
      application in production of glutamic acid.
AB  - A halo-tolerant glutaminase gene (BlglsA) was isolated from Bacillus
      licheniformis. Heterologous expression of BlglsA revealed that it encodes for a
      36 kDa protein containing 327 amino acid residues. The purified enzyme showed
      optimal activity at a pH of 9.5 while 35  degrees C was found to be the optimum
      temperature. The enzyme retained about 92 and 97% stability at pH 12 and
      temperature (40  degrees C) respectively. Subsequent immobilization of BlglsA on
      nano magnetic cellulose sheet (NMCS) led to an enhanced tolerance to higher
      temperature. NMCS-BlglsA showed optimum activity at 45  degrees C, although it
      was stable even at 60  degrees C. NaCl tolerance (>=90% in 0.3 M) was almost
      similar to BlglsA and NMCS-BlglsA. The metal ions Fe2+ (5 mM) and Mn2+ (2.5 mM)
      improved the BlglsA relative activity by 61 and 48%, respectively. In contrast, 5
      mM Mn2+ was found suitable to enhance the activity of NMCS-BlglsA up to 72%. The
      production of glutamic acid by NMCS-BlglsA was 1.61 g/l in 48 h. Reusability test
      of NMCS-BlglsA showed 76 and 35% retention of the actual activity after 4th and
      7th cycle, respectively. Such remarkable biochemical properties of NMCS-BlglsA
      make it an attractive enzyme for food industries.

PMID- 30096400
TI  - In vitro anti-Leishmania activity of T6 synthetic compound encapsulated in yeast
      derived beta-(1,3)-d-glucan particles.
AB  - The objective of this study was to encapsulate a synthetic compound, the 4-[(2E)
      N'-(2,2'-bithienyl-5-methylene)hydra-zinecarbonyl]-6,7-dihydro-1-phenyl-1H
      pyrazolo[3,4-d]pyridazin-7-one (T6) in glucan-rich particles mainly composed by
      the cell wall of Saccharomyces cerevisiae (GPs) and to study their individual and
      combined activity on Leishmania infantum. The possible mechanism of action of T6
      was also investigated. Our results showed the activity of T6 compound in both
      promastigote (IC50 = 2.5 MUg/mL) and intracellular amastigote (IC50 = 1.23
      MUg/mL) forms. We also found activity against intracellular amastigote forms
      (IC50 = 8.20 MUg/mL) when the T6 compound was encapsulated in GPs. Another
      interesting finding was the fact that T6 encapsulated in GPs showed a significant
      decrease in J774A1 macrophage toxicity (CC50 >= 18.53 MUg/mL) compared to the T6
      compound alone (IC50 = 2.27 MUg/mL). Through electron microscopy and biochemical
      methodologies, we verified that the activity of T6 in promastigote forms of L.
      infantum was characterized by events of cell death by apoptosis like increased
      ROS production, cell shrinkage, phosphatidylserine exposure and DNA
      fragmentation. We conclude that T6 can be considered a promising anti-Leishmania
      compound, and that the use of GPs for drug encapsulation is an interesting
      approach to the development of new effective and less toxic formulations.

PMID- 30096401
TI  - Nanotechnology-mediated immunochemotherapy combined with docetaxel and PD-L1
      antibody increase therapeutic effects and decrease systemic toxicity.
AB  - Immunotherapy has exhibited enormous practice in the treatment of melanoma
      because of the intrinsic properties of tumor. Tumor can downmodulate immune
      function via multiple mechanisms such as immune checkpoint pathways. The PD-L1
      monoclonal antibodies that block the PD1/PD-L1 pathway, which induced tumor cells
      to evade an immune attack, can delay tumor growth efficiently with inevitable
      disadvantages such as low selectivity and systemic toxicity. Nanomedicine is
      clearly an approach that holds tremendous potential for addressing the
      shortcomings and assisting delivery of drugs with proper biodistribution. Herein,
      we developed a smart nanoplatform with precisely active targeting liposome co
      loaded chemotherapy and immunotherapy drugs for synergistic antitumor effects
      while decreasing systemic toxicity. Immunoliposomes have stable pharmaceutical
      properties and show a significant antitumor effect in vivo and in vitro. Cellular
      uptake in vitro and biodistribution in vivo demonstrated that immunoliposomes
      could be delivered and accumulated more in tumor tissues. These immunoliposomes
      exhibited effective tumor inhibition and prolonged survival time due to
      activation of tumor-specific CD8+ T cell and highly selective tumor killing. In
      addition, safety evaluation of liposomes also demonstrated their increased tumor
      accumulation and decreased systemic toxicity. Hence, this smart pH-sensitive
      nanoplatform has promising potential for clinical applications and possibly
      provides a well-controlled design for combination of chemotherapy with various
      immunotherapies for further exploration.

PMID- 30096402
TI  - Antiglioma via regulating oxidative stress and remodeling tumor-associated
      macrophage using lactoferrin-mediated biomimetic codelivery of
      simvastatin/fenretinide.
AB  - Effective treatment of malignant glioma still remains a formidable challenge due
      to lack of the effective BBB-permeable drugs and efficient brain delivery
      methods, and the pharmacotherapy options are very limited. Therefore, to develop
      an effective therapeutic strategy is a pressing need. In this work, a
      noncytotoxic drug combination (i.e., simvastatin and fenretinide) was revealed to
      be potent for treating glioma, which was co-encapsulated into a TPGS-TAT-embedded
      lactoferrin nanoparticle system for achieving brain-targeted biomimetic delivery
      via the LRP-1 receptor. It was shown that the lactoferrin nanoparticle
      repolarized the tumor-associated macrophages from the M2 phenotype to M1 via
      regulating the STAT6 pathway, as well as induced the ROS-mediated mitochondrial
      apoptosis by inhibiting the Ras/Raf/p-Erk pathway in the glioma cells. The
      antiglioma efficacy was further demonstrated in both the subcutaneous and
      orthotopic glioma models. The repolarization of tumor-associated macrophages not
      only prompted the ROS generation but also induced the innate immunity (e.g.,
      antitumor cytokine release). This delivery and therapeutic strategy provides a
      novel modality for the glioma treatment.

PMID- 30096403
TI  - Osmotic and electroosmotic fluid transport across the retinal pigment epithelium:
      A mathematical model.
AB  - The retinal pigment epithelium (RPE) is the outermost cell layer of the retina.
      It has several important physiological functions, among which is removal of
      excess fluid from the sub-retinal space by pumping it isotonically towards the
      choroid. Failure of this pumping leads to fluid accumulation, which is closely
      associated with several pathological conditions, such as age-related macular
      degeneration, macular oedema and retinal detachment. In the present work we study
      mechanisms responsible for fluid transport across the RPE with the aim of
      understanding how fluid accumulation can be prevented. We focus on two possible
      mechanisms, osmosis and electroosmosis, and develop a spatially resolved
      mathematical model that couples fluid and ion transport across the epithelium,
      accounting for the presence of Na+,K+ and Cl- ions. Our model predicts spatial
      variability of ion concentrations and the electrical potential along the cleft
      gap between two adjacent cells, which osmotically drives the flow across the
      lateral membranes. This flow is directed from the sub-retinal space to the
      choroid and has a magnitude close to measured values. Electroosmosis is
      subdominant by three orders of magnitude to osmosis and has an opposite
      direction, suggesting that local osmosis is the main driving mechanism for water
      transport across the RPE.

PMID- 30096404
TI  - Effects of random motion in traveling and grazing herds.
AB  - We examine the role that randomness or noise in individual motion may play in
      forming effective grazing strategies for herd members as they collectively move
      toward a destination. Through a model where animals are attracted to Voronoi
      neighbors as well as a destination endpoint, we show that including a significant
      random motion component can speed up the movement of a herd toward this
      destination, increase the efficiency that food is acquired during the travel, and
      facilitate a natural herd shape that mitigates predation risk. Specifically, if
      the influence of the Voronoi neighbors on individual motion is equal to the pull
      toward the destination, we find that optimal travel time and food consumption
      efficiency occurs for noise approximately twice as strong as the influence of
      herd members to each other, in a range of herd sizes from 10 to 100. We find that
      reducing the destination influence lowers this optimal noise only slightly, with
      random motion still exceeding the influence of neighbors. For a destination
      influence exceeding that of the Voronoi neighbors, an additional travel mode
      appears with minimal noise and aligned velocities in which the herd marches
      directly toward the endpoint. Our results are consistent with observational
      evidence of random motion in several animal groups, and motivate its
      generalization to traveling and grazing herds.

PMID- 30096405
TI  - Genome-wide haplotype association study identifies risk genes for non-small cell
      lung cancer.
AB  - Lung cancer is the leading cause of cancer-related death worldwide. Most lung
      cancer is non-small cell lung cancer (NSCLC), in which malignant cells form in
      the lung epithelium. Mutations in multiple genes and environmental factors both
      contribute to NSCLC, and although some NSCLC susceptibility genes have been
      characterized, the pathogenesis of this disease remains unclear. To identify
      genes conferring NSCLC risk and determine their associated pathological
      mechanism, we combined genome-wide haplotype associated analysis with gene
      prioritization using 224,677 SNPs in 37 NSCLC cell lines and 116 unrelated
      European individuals. Five candidate genes were identified: ESR1, TGFBR1, INSR,
      CDH3, and MAP3K5. All of these have previously been implicated in NSCLC, with the
      exception of CDH3, which can therefore be considered a novel indicator of NSCLC
      risk. Functional annotation confirmed the relationship between these five genes
      and NSCLC. Our findings are indicative of the underlying pathological mechanisms
      of NSCLC and provide information to support future directions in diagnosing and
      treating NSCLC.

PMID- 30096406
TI  - Non-canonical processing of DNA photodimers with Bacillus subtilis UV
      endonuclease YwjD, 5'->3' exonuclease YpcP and low-fidelity DNA polymerases YqjH
      and YqjW.
AB  - It has been shown that mutation frequency decline (Mfd) and nucleotide excision
      repair (NER) deficiencies promote UV-induced mutagenesis in B. subtilis
      sporangia. As replication is halted in sporulating B. subtilis cells, in this
      report, we investigated if this response may result from an error-prone repair
      event involving the UV-endonuclease YwjD and low fidelity (LF) DNA synthesis.
      Accordingly, disruption of YwjD generated B. subtilis sporangia that were more
      susceptible to UV-C radiation than sporangia of the WT strain and such
      susceptibility increased even more after the single or simultaneous inactivation
      of the LF DNA polymerases YqjH and YqjW. To further explore this concept,
      functional His6-tagged YwjD and Y-DNA polymerases YqjH and YqjW were produced and
      purified to homogeneity. In vitro repair assays showed that YwjD hydrolyzed the
      phosphodiester bond immediately located 5'-end of a ds-DNA substrate bearing
      either, cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PD) or Dewar
      isomers (DWI). Notably, the 6-4 PD and DWI but not the CPDs repair intermediaries
      of YwjD were efficiently processed by the LF polymerase YqjH suggesting that an
      additional 5'->3' exonuclease event was necessary to process PD. Accordingly, the
      LF polymerase YqjW efficiently processed the incision-excision repair products
      derived from YwjD and exonuclease YpcP attack over CPD-containing DNA. In
      summary, our results unveiled a novel non-canonical repair pathway that employs
      YwjD to incise PD-containing DNA and low fidelity synthesis contributing thus to
      mutagenesis, survival and spore morphogenesis in B. subtilis.

PMID- 30096407
TI  - The nuclear receptor NOR-1 modulates redox homeostasis in human vascular smooth
      muscle cells.

PMID- 30096408
TI  - Sympathoadrenergic suppression improves heart function by upregulating the ratio
      of sRAGE/RAGE in hypertension with metabolic syndrome.
AB  - Receptors-for-Advanced-Glycation-End-products (RAGE) activate pro-inflammatory
      programs mediated by carboxymethyllysine (CML) and high-mobility-group-box1
      protein (HMGB1). The soluble isoform sRAGE neutralizes RAGE-ligands preventing
      cardiovascular complications in conditions associated with increased sympathetic
      activation like hypertension and diabetes. The effects of sympathetic modulation
      on RAGE/sRAGE-balance and end-organ damage in metabolic syndrome on top of
      hypertension remains unknown. We hypothesized that increased sympathoadrenergic
      activity might lead to an unfavourable RAGE/sRAGE regulation. Renal denervation
      (RDN) was used to modulate sympathetic activation in obese spontaneously
      hypertensive rats (SHRobRDN) versus sham-operated obese spontaneously
      hypertensive rats (SHRob), their hypertensive lean controls (SHR) and non
      hypertensive controls. Cardiac fibrosis was assessed by histological analysis and
      sRAGE/RAGE and ligand levels by Western blotting. Levels of CML and HMGB1 were
      highest in SHRob and were significantly lowered by RDN in serum (-44% and -45%)
      and myocardium (-25% and -52%). Myocardial RAGE was increased in SHR (+72% versus
      controls) and in SHRob (+68% versus SHR) while sRAGE decreased (-50% in SHR
      versus controls and -51% in SHRob versus SHR). RDN reduced myocardial RAGE
      expression. (-20%) and increased sRAGE levels in heart (+80%) and serum (+180%)
      versus sham-operated SHRob. Myocardial fibrosis correlated inversely with
      myocardial sRAGE content (r = -0.79; p = .004; n = 10). Myocardial sRAGE shedding
      active A-Disintegrin-And-Metalloprotease-10 (ADAM-10) was decreased in SHR (-33%
      versus controls) and in SHRob (-54% versus SHR), and was restored after RDN
      (+129% versus SHRob). Serum ADAM-10 activity was also decreased in SHRob (-66%
      versus SHR) and restored after RDN (+150% versus SHRob). In vitro, isoproterenol
      induced a beta1-adrenergic receptor mediated increase of RAGE expression in
      splenocytes (+200%) and decreased sRAGE secretion of splenocytes and cardiac
      fibroblasts (-50% and -49%) by beta2-adrenergic receptor stimulation mediated
      suppression of ADAM-10 activity. In conclusion, sympathetic activity affects
      sRAGE/RAGE-balance, which can be suppressed through sympathetic modulation by
      RDN, preventing RAGE-induced cardiac damage in hypertension with metabolic
      syndrome.

PMID- 30096409
TI  - Interleukin-17 enhances cardiac ventricular remodeling via activating MAPK
      pathway in ischemic heart failure.
AB  - BACKGROUND: We aimed to investigate the impact of interleukin (IL)-17 on
      ventricular remodeling and the genesis of ventricular arrhythmia (VA) in an
      ischemic heart failure (HF) model. The expression of the proinflammatory cytokine
      IL-17 is upregulated during myocardial ischemia and plays a fundamental role in
      post-infarct inflammation. However, the influence of IL-17 on the genesis of VA
      has not yet been studied. METHODS AND RESULTS: The level of inflammation and Th17
      cell (CD4+IL-17+) expression in the rabbit model of ischemic HF were studied by
      flow cytometry, quantitative polymerase chain reaction (qPCR), and enzyme-linked
      immunosorbent assay (ELISA). The effect of IL-17 on VA induction following acute
      and chronic administration of IL-17 was determined using electrophysiological
      techniques and optical mapping. The expression of IL-17 target genes and related
      cytokines and chemokines in vivo and in vitro were measured using qPCR, ELISA,
      and immunoblotting. Th17 cells were markedly increased in the ischemic HF rabbit
      model. IL-17 directly induced VA in vivo and in vitro in a dose-dependent manner.
      IL-17 decreased conduction velocity, lengthened action potential duration, and
      increased the slope of the left ventricle (LV) restitution curve. IL-17 treatment
      led to fibrosis, collagen production and apoptosis in the LV. Furthermore,
      increased IL-17 signaling activated mitogen-activated protein kinase and
      increased the expression of downstream target genes, IL-6, TNF, CCL20, and CXCL1.
      An anti-IL-17 neutralizing antibody abolished the effects of IL-17. CONCLUSIONS:
      The expression of IL-17 and its downstream target genes may play fundamental
      roles in inducing VA in ischemic HF.

PMID- 30096410
TI  - Expression and regulation of the BKRF2, BKRF3 and BKRF4 genes of Epstein-Barr
      virus.
AB  - The BKRF2, BKRF3 and BKRF4 genes of Epstein-Barr virus (EBV) are located close
      together in the viral genome, which encode glycoprotein L, uracil-DNA glycosylase
      and a tegument protein, respectively. Here, we demonstrate that the BKRF2 gene
      behaves as a true-late lytic gene, whereas the BKRF3 and BKRF4 genes belong to
      the early lytic gene family. Our results further reveal that both BKRF3 and BKRF4
      promoters are new synergistic targets of Zta and Rta, two EBV latent-to-lytic
      switch transactivators. Multiple Rta- and Zta-responsive elements within the
      BKRF3 and BKRF4 promoters were identified and characterized experimentally.
      Importantly, we show that DNA methylation is absolutely required for activation
      of the BKRF4 promoter by Zta alone or in combination with Rta. Moreover, we find
      that sodium butyrate, an inducing agent of EBV reactivation, is capable of
      activating the BKRF4 promoter through a mechanism independent of Zta and Rta.
      Overall, our studies highlight the complexity of transcriptional regulation of
      lytic genes within the BKRF2-BKRF3-BKRF4 gene locus.

PMID- 30096411
TI  - Identification of adenovirus neutralizing antigens using capsid chimeric viruses.
AB  - Human adenoviruses (HAdV) 3 and 7 can cause acute respiratory disease epidemics
      and outbreaks. Identification of neutralizing epitopes is vital for surveillance
      and vaccine development. In this study, we generated the recombinant capsid
      chimeric human adenoviruses rAd3E-Fk7, containing the Ad3E backbone and the HAdV
      7 fiber knob, and rAd3E-H7Fk7, which contain an Ad3E backbone but HAdV-7 hexon
      and fiber knob. In vitro neutralization tests with these chimeric adenoviruses
      using both mouse and human antisera indicated that hexon and fiber knob are the
      major targets recognized by neutralizing antibodies against HAdV-3 or HAdV-7, and
      other capsid proteins including the penton base and fiber shaft may not
      contribute to neutralizing antibody responses. In conclusion, both hexon and
      fiber knob structures in HAdV-3 and HAdV-7 may be the proteins which induce
      neutralizing antibody responses and thus may be important for adenovirus vaccine
      and drug development.

PMID- 30096412
TI  - Rapid evolutionary dynamics of pepper mild mottle virus.
AB  - Pepper mild mottle virus (PMMoV) is one of the most destructive pathogens of
      pepper crops and has major impacts on global crop yields. Some aspects of the
      molecular biology of PMMoV have been studied intensively, but estimates of its
      evolutionary rate have shown considerable variation. We investigated the
      phylodynamics of PMMoV by analysing 171 nucleotide sequences of the coat protein
      gene, sampled between 1980 and 2016. Our Bayesian phylogenetic analyses, using
      the structured coalescent, dated the crown group to 1949 (95% credibility
      interval 1935-1962). We reveal that PMMoV has been evolving at a rate of 9.363 *
      10-4 substitutions/site/year (95% credibility interval 7.362 * 10-4-1.138 * 10
      3). This is similar to evolutionary rates estimated for animal RNA viruses,
      indicating that PMMoV has been undergoing rapid evolutionary dynamics.

PMID- 30096413
TI  - An item's status in semantic memory determines how it is recognized: Dissociable
      patterns of brain activity observed for famous and unfamiliar faces.
AB  - Are all faces recognized in the same way, or does previous experience with a face
      change how it is retrieved? Previous research using human scalp-recorded Event
      Related Potentials (ERPs) demonstrates that recognition memory can produce
      dissociable brain signals under a variety of circumstances. While many studies
      have reported dissociations between the putative 'dual processes' of familiarity
      and recollection, a growing number of reports demonstrate that recollection
      itself may be fractionated into component processes. Many recognition memory
      studies using lexical materials as stimuli have reported a left parietal ERP
      old/new effect for recollection; however, when unfamiliar faces are recollected,
      an anterior effect can be observed. This paper addresses two separate hypotheses
      concerning the functional significance of the anterior old/new effect: perceptual
      retrieval and semantic status. The perceptual retrieval view is that the anterior
      effect reflects reinstatement of perceptual information bound up in an episodic
      representation, while the semantic status view is that information not
      represented in semantic memory pre-experimentally elicits the anterior effect
      instead of the left parietal effect. We tested these two competing accounts by
      investigating recognition memory for unfamiliar faces and famous faces in two
      separate experiments, in which same or different pictures of studied faces were
      presented as test items to permit brain activity associated with retrieving face
      and perceptual information to be examined independently. The difference in neural
      activity between same and different picture hits was operationalized as a pattern
      of activation associated with perceptual retrieval; while the contrast between
      different picture hits and correct rejection of new faces was assumed to reflect
      face retrieval. In Experiment 1, using unfamiliar faces, the anterior old/new
      effect (500-700 ms) was observed for face retrieval but not for perceptual
      retrieval, challenging the perceptual retrieval hypothesis. In Experiment 2,
      using famous faces, face retrieval was associated with a left parietal effect
      (500-700 ms), supporting the semantic representation hypothesis. A between
      subjects analysis comparing scalp topography across the two experiments found
      that the anterior effect observed for unfamiliar faces is dissociable from the
      left parietal effect found for famous faces. This pattern of results supports the
      hypothesis that an item's status in semantic memory determines how it is
      recognized.

PMID- 30096415
TI  - Exogenous Vitamin D signaling alters skeletal patterning, differentiation, and
      tissue integration during limb regeneration in the axolotl.
AB  - Urodele amphibians such as the axolotl regenerate complete limbs as adults, and
      understanding how the "blueprint", or pattern, of the regenerate is established
      and manipulated are areas of intense interest. Nutrient signaling plays an
      important role in pattern formation during regeneration. Retinoic acid signaling
      is the most characterized pathway during this process. Exogenous retinoic acid
      (RA) reprograms the pattern information in regenerating cells to a more
      posterior, ventral, and proximal identity. Vitamin D signaling shares several
      molecular similarities with RA and has been shown to alter pattern formation
      during zebrafish pectoral fin regeneration. To determine if exogenous Vitamin D
      signaling is capable of reprograming pattern in the axolotl limb blastema, we
      treated regenerating limbs with a potent Vitamin D agonist. Under the studied
      conditions, exogenous Vitamin D did not act in a manner similar to RA and failed
      to proximalize the pattern of the resulting regenerates. The Vitamin D treatment
      did result in several skeletal defects during regeneration, including carpal
      fusions along the A/P axis; failure to integrate the newly regenerated tissue
      with the existing tissue, formation of ectopic nodules of cartilage at the site
      of amputation, and altered bone morphology in uninjured skeletal tissue.

PMID- 30096416
TI  - An in vitro method for studying subcellular rearrangements during cell
      polarization in Drosophila melanogaster hemocytes.
AB  - Thanks to the power of Drosophila genetics, this animal model has been a precious
      tool for scientists to uncover key processes associated to innate immunity. The
      fly immune system relies on a population of macrophage-like cells, also referred
      to as hemocytes, which are highly migratory and phagocytic, and can easily be
      followed in vivo. These cells have shown to play important roles in fly
      development, both at the embryonic and pupal stages. However, there is no robust
      assay for the study of hemocyte migration in vitro, which limits our
      understanding of the molecular mechanisms involved. Here, we contribute to fill
      this gap by showing that hemocytes adopt a polarized morphology upon ecdysone
      stimulation, allowing the study of the cytoskeleton rearrangements and organelle
      reorganization that take place during the first step of cell locomotion.

PMID- 30096414
TI  - Basal forebrain cholinergic system volume is associated with general cognitive
      ability in the elderly.
AB  - OBJECTIVE: At the present, it is unclear whether association of basal forebrain
      cholinergic system (BFCS) volume with cognitive performance exists in healthy as
      well as in cognitively impaired elderly subjects. Whereas one small study
      reported an association of BFCS volume with general cognitive ability 'g' in
      healthy ageing, effects on specific cognitive domains have only been found in
      subjects with cognitive decline. Here we aim to clarify whether an association of
      BFCS volume and 'g' is present in a larger sample of elderly subjects without
      obvious symptoms of dementia and whether similar associations can also be
      observed in specific cognitive domains. METHODS: 282 pre-surgical patients from
      the BioCog study (aged 72.7 +/- 4.9 years with a range of 65-87 years, 110 women)
      with a median MMSE score of 29 points (range 24-30) were investigated. BFCS and
      brain volume as well as brain parenchymal fraction were assessed in T1-weighted
      MR images using SPM12 and a probabilistic map of the BFCS. Neuropsychological
      assessment comprised the CANTAB cognitive battery and paper-and-pencil based
      tests. For data analysis, generalised linear models and quantile regression were
      applied. RESULTS: Significant associations of BFCS volume with 'g' and several
      cognitive domains were found, with the strongest association found for 'g'. BFCS
      volume explained less variance in cognitive performance than brain volume. The
      association was not confounded by brain parenchymal fraction. Furthermore, the
      association of BFCS volume and 'g' was similar in high- and low-performers.
      CONCLUSION: Our results extend previous study findings on BFCS volume
      associations with cognition in elderly subjects. Despite the observed
      associations of BFCS volume and cognitive performance, this association seems to
      reflect a more general association of brain volume and cognition. Accordingly, a
      specific association of BFCS volume and cognition in non-demented elderly
      subjects is questionable.

PMID- 30096418
TI  - Reply to: "Response to 'Rethinking biotin therapy for hair, nail, and skin
      disorders'".

PMID- 30096417
TI  - Current time-to-positivity of blood cultures in febrile neutropenia: a tool to be
      used in stewardship de-escalation strategies.
AB  - OBJECTIVES: We aimed to describe the current time-to-positivity (TTP) of blood
      cultures in individuals with onco-haematological diseases with febrile
      neutropenia. We assessed the probability of having a multidrug-resistant Gram
      negative bacilli (MDR-GNB) bloodstream infection (BSI) 24 h after cultures were
      taken, to use this information for antibiotic de-escalation strategies. METHODS:
      BSI episodes were prospectively collected (2003-2017). When a patient experienced
      more than one BSI, only one episode was randomly chosen. Time elapsed from the
      beginning of incubation to a positive reading was observed; TTP was recorded when
      the first bottle had a positive result. RESULTS: Of the 850 patient-unique
      episodes, 323 (38%) occurred in acute leukaemia, 185 (21.8%) in non-Hodgkin's
      lymphoma and 144 (16.9%) in solid neoplasms. Coagulase-negative staphylococci
      (225; 26.5%), Escherichia coli (207; 26.1%), Pseudomonas aeruginosa (136; 16%),
      Enterococcus spp. (81; 9.5%) and Klebsiella pneumoniae (67; 7.9%), were the most
      frequent microorganisms isolated. MDR-GNB were documented in 126 (14.8%)
      episodes. Median TTP was 12 h (interquartile range 9-16.5 h). Within the first 24
      h, 92.1% of blood cultures were positive (783/850). No MDR-GNB was positive over
      24 h. Of the 67 (7.9%) episodes with a TTP >=24 h, 25 (37.3%) occurred in
      patients who were already receiving active antibiotics against the isolated
      pathogen. Most common isolations with TTP >=24 h were coagulase-negative
      staphylococci, candidaemia and a group of anaerobic GNB. CONCLUSIONS: Currently,
      the vast majority of BSI in individuals with onco-haematological diseases with
      febrile neutropenia have a TTP <24 h, including all episodes caused by MDR-GNB.
      Our results support reassessing empiric antibiotic treatment in neutropenic
      patients at 24 h, to apply antibiotic stewardship de-escalation strategies.

PMID- 30096419
TI  - Response to: "Rethinking biotin therapy for hair, nail, and skin disorders".

PMID- 30096420
TI  - Reply to "The ethical issue of 'cherry picking' patients".

PMID- 30096421
TI  - Comments on "Short-term reasons for withdrawal and adverse events associated with
      apremilast therapy for psoriasis in real-world practice compared with in clinical
      trials: A multicenter retrospective study".

PMID- 30096422
TI  - Response to a letter to the editor regarding "The ethical issue of "cherry
      picking" patients".

PMID- 30096424
TI  - Metabolic engineering of Escherichia coli for high-level astaxanthin production
      with high productivity.
AB  - Astaxanthin is a reddish keto-carotenoid classified as a xanthophyll found in
      various microbes and marine organisms. As a powerful antioxidant having up to 100
      times more potency than other carotenoids such as beta-carotene, lutein, and
      lycopene, astaxanthin is a versatile compound utilized in animal feed, food
      pigment, health promotion and cosmetic industry. Here, we report development of
      metabolically engineered Escherichia coli capable of producing astaxanthin to a
      high concentration with high productivity. First, the heterologous crt genes
      (crtE, crtY, crtI, crtB, and crtZ) from Pantoea ananatis and the truncated BKT
      gene (trCrBKT) from Chlamydomonas reinhardtii were introduced to construct the
      astaxanthin biosynthetic pathway. Then, eight different fusion tags were examined
      by attaching them to the N- or C-terminus of the trCrBKT membrane protein to
      allow stable expression and to efficiently guide trCrBKT to the E. coli membrane.
      When the signal peptide of OmpF and TrxA were tagged to the N-terminus and C
      terminus of trCrBKT, respectively, astaxanthin production reached 12.90 mg/L
      (equivalent to 3.84 mg/gDCW), which was 2.08-fold higher than that obtained
      without tagging. Upon optimization of culture conditions, this engineered strain
      WLGB-RPP harboring pAX15 produced 332.23 mg/L (5.38 mg/gDCW) of astaxanthin with
      the productivity of 3.79 mg/L/h by fed-batch fermentation. In order to further
      increase astaxanthin production, in silico flux variability scanning based on
      enforced objective flux (FVSEOF) was performed to identify gene overexpression
      targets. The engineered strain WLGB-RPP (pAX15, pTrc-ispDF) which simultaneously
      overexpressing the ispD and ispF genes identified by FVSEOF produced astaxanthin
      to a higher concentration of 377.10 mg/L (6.26 mg/gDCW) with a productivity of
      9.20 mg/L/h upon induction with 1 mM IPTG. When cells were induced with 0.5 mM
      IPTG to reduce the metabolic burden, astaxanthin concentration further increased
      to 432.82 mg/L (7.12 mg/gDCW) with a productivity of 9.62 mg/L/h. To more stably
      maintain plasmid during the fed-batch fermentation of WLGB-RPP (pAX15, pTrc
      ispDF), the post-segregational killing hok/sok system was introduced. This strain
      produced 385.04 mg/L (6.98 mg/gDCW) of astaxanthin with a productivity of 7.86
      mg/L/h upon induction with 0.5 mM IPTG. The strategies reported here will be
      useful for the enhanced production of astaxanthin and related carotenoid products
      by engineered E. coli strains.

PMID- 30096425
TI  - Boosting heterologous protein production yield by adjusting global nitrogen and
      carbon metabolic regulatory networks in Bacillus subtilis.
AB  - Bacillus subtilis is extensively applied as a microorganism for the high-level
      production of heterologous proteins. Traditional strategies for increasing the
      productivity of this microbial cell factory generally focused on the targeted
      modification of rate-limiting components or steps. However, the longstanding
      problems of limited productivity of the expression host, metabolic burden and non
      optimal nutrient intake, have not yet been completely solved to achieve
      significant production-strain improvements. To tackle this problem, we
      systematically rewired the regulatory networks of the global nitrogen and carbon
      metabolism by random mutagenesis of the pleiotropic transcriptional regulators
      CodY and CcpA, to allow for optimal nutrient intake, translating into
      significantly higher heterologous protein production yields. Using a beta
      galactosidase expression and screening system and consecutive rounds of
      mutagenesis, we identified mutant variants of both CodY and CcpA that in
      conjunction increased production levels up to 290%. RNA-Seq and electrophoretic
      mobility shift assay (EMSA) showed that amino acid substitutions within the DNA
      binding domains altered the overall binding specificity and regulatory activity
      of the two transcription factors. Consequently, fine-tuning of the central
      metabolic pathways allowed for enhanced protein production levels. The improved
      cell factory capacity was further demonstrated by the successfully increased
      overexpression of GFP, xylanase and a peptidase in the double mutant strain.

PMID- 30096423
TI  - Association between the EPHX2 p.Lys55Arg polymorphism and prognosis following an
      acute coronary syndrome.
AB  - Inhibition of soluble epoxide hydrolase (sEH, EPHX2) elicits potent
      cardiovascular protective effects in preclinical models of ischemic
      cardiovascular disease (CVD), and genetic polymorphisms in EPHX2 have been
      associated with developing ischemic CVD in humans. However, it remains unknown
      whether EPHX2 variants are associated with prognosis following an ischemic CVD
      event. We evaluated the association between EPHX2 p.Lys55Arg and p.Arg287Gln
      genotype with survival in 667 acute coronary syndrome (ACS) patients. No
      association with p.Arg287Gln genotype was observed (P = 0.598). Caucasian EPHX2
      Arg55 carriers (Lys/Arg or Arg/Arg) had a significantly higher risk of 5-year
      mortality (adjusted hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.01
      2.55, P = 0.045). In an independent population of 2712 ACS patients, this
      association was not replicated (adjusted HR 0.92, 95% CI 0.70-1.21, P = 0.559).
      In a secondary analysis, Caucasian homozygous Arg55 allele carriers (Arg/Arg)
      appeared to exhibit a higher risk of cardiovascular mortality (adjusted HR 2.60,
      95% CI 1.09-6.17). These results demonstrate that EPHX2 p.Lys55Arg and
      p.Arg287Gln polymorphisms do not significantly modify survival after an ACS
      event. Investigation of other sEH metabolism biomarkers in ischemic CVD appears
      warranted.

PMID- 30096426
TI  - Ruptured Iliac Pseudoaneurysm after Intravesical Bacillus Calmette-Guerin: Urgent
      Endovascular Treatment. Case Report and Literature Review.
AB  - BACKGROUND: Ruptured mycotic aneurysms are an extremely rare complication of
      intravesical Bacillus Calmette-Guerin (BCG) immunotherapy. Several cases
      involving various arterial sites, mostly in the thoracic or abdominal aorta, have
      been described in the literature. BCG immunotherapy rarely causes false aneurysms
      and open surgical repair using an in situ prosthetic graft is most commonly
      performed. Further to this, targeted antituberculous treatment is required for at
      least one year following surgery. METHODS: A 69-year-old man presented at our
      clinic with fever, lower back pain and malaise. One year before admission he was
      treated, again, with intravesical BCG for recurrence of a carcinoma. RESULTS: A
      large infected pseudoaneurysm of 115mm was treated with the implantation of an
      aortouniiliac endoprosthesis followed by a crossover femoro-femoral bypass and
      surgical resection of the mass via an retroperitoneal approach. CONCLUSIONS:
      Endovascular repair can be considered a valid option in an emergency. A hybrid
      approach was chosen due to the need for urgent action and the poor condition of
      the patient who was haemodynamically unstable. In particular, the implantation of
      an aortouniiliac endoprosthesis at the level of the contralateral iliac axis
      allowed us to avoid the release of an endoprosthesis at the infected area level.
      Close patient follow-up with clinical evaluation every three months and a CT-scan
      yearlyis mandatory following the intervention and during antibiotic therapy. A
      systematic review of the literature has been subsequently carried out on this
      specific clinical case, highlighting 47 cases described from 1988. CASE REPORT: A
      large infected pseudoaneurysm of 115 mm presented at our clinic was treated with
      the implantation of an aortouniiliac endoprosthesis followed by a crossover
      femoro-femoral bypass and surgical resection of the mass via a retroperitoneal
      approach. CONCLUSIONS: Endovascular repair can be considered a valid option in an
      emergency. A hybrid approach was chosen due to the need for urgent action and the
      poor condition of the patient who was hemodynamically unstable. In particular,
      the implantation of an aortouniiliac endoprosthesis at the level of the
      contralateral iliac axis allowed us to avoid the release of an endoprosthesis at
      the infected area level. Close patient follow-up with clinical evaluation every 3
      months and a computed tomography scan yearly is mandatory following the
      intervention and during antibiotic therapy. A systematic review of the literature
      has been subsequently carried out on this specific clinical case, highlighting 47
      cases described from 1988.

PMID- 30096427
TI  - Outcomes Comparison Between Ligation and Repair after Major Lower Extremity
      Venous Injury.
AB  - BACKGROUND: The necessity of repair remains controversial after major lower
      extremity venous injuries (MLEVIs). Ligation may cause venous hypertension which
      should be managed with fasciotomies. Previous studies have shown that fasciotomy
      rate is not affected by the type of management of MLEVIs. The aim of this study
      was to examine the rate of fasciotomy, amputation, and other complications from a
      difference between ligation and repair of MLEVIs. METHODS: The National Trauma
      Data Bank (NTDB) for 2010-2014 was reviewed. Eligible patients were restricted to
      MLEVI patients who underwent surgical ligation or repair. Data on demographics,
      rate of fasciotomy, secondary amputation, and other complications were collected.
      Comparative analysis between ligation and repair on demographics, complications,
      and outcomes was performed using multivariate logistic regression models.
      RESULTS: A total of 2120 patients were identified in NTDB and 1029 (48.5%)
      underwent ligation while 1091 (51.5%) underwent repair. The overall rate of
      fasciotomy and secondary amputation was 38.9% (n = 824) and 4.8% (n = 101),
      respectively. Patients in the ligation group had a higher proportion of
      university hospital setting and penetrating injury. Otherwise, there was no
      significant difference in other characteristics between the 2 groups. Patients in
      the ligation group had significantly higher rates of fasciotomy and secondary
      amputation and longer hospital length of stay (LOS) than those in the repair
      group (44.6% vs. 33.5%, risk ratio [RR] 1.33, 6.1% vs. 3.4%, RR 1.81, 11 [6-20]
      vs. 9 [5-17], respectively). Otherwise, there was no significant difference in
      all other complications and in-hospital mortality between 2 groups. CONCLUSIONS:
      The fasciotomy rate was surprisingly high and affected by venous ligation in
      patients with MLEVIs. Considering the overall physiological condition, trauma
      surgeons should perform venous repair aggressively and prepare judiciously for
      fasciotomy after surgery. Avoiding venous ligation and maintaining venous outflow
      may contribute to not only reducing the need for fasciotomy and LOS but also
      saving limbs.

PMID- 30096428
TI  - A Cost Calculation of EVAR and FEVAR Procedures at an European Academic Hospital.
AB  - BACKGROUND: The aim was to calculate the costs of EVAR and FEVAR procedures in a
      European academic hospital by cost retrieval based on a subcohort with known
      detailed costs through application of the individually detailed calculated costs
      to the total study population and to correlate these with corresponding
      reimbursements. METHODS: A cost analysis was performed on 25 FEVAR and 100 EVAR
      cases based on the detailed cost analysis of a group of patients treated in 2012
      and 2013 by applying the costs based on costs per time unit within 4 subgroups:
      (1) uncomplicated EVAR, (2) complicated EVAR, (3) uncomplicated FEVAR, and (4)
      complicated FEVAR. RESULTS: Thirty cases (19 EVAR and 11 FEVAR) treated in 2012
      and 2013 were used to determine the individual detailed costs for the entire
      study group consisting of 100 EVAR and 25 FEVAR cases. There were 14 repeat
      operations within the 100 EVAR cases and 3 repeat operations within the 25 FEVAR
      cases. A total of 14 EVAR-treated patients were readmitted, as was one FEVAR
      patient. The costs of the endografts were the largest contributor to the overall
      costs, followed by the costs of the surgery itself and the stay in the ward. The
      costs of an uncomplicated EVAR procedure summed up at ?12,090; a complicated EVAR
      procedure costs ?13,956. An uncomplicated FEVAR procedure costs ?34,807, and a
      complicated FEVAR procedure costs ?36,695. The difference between median
      reimbursements received for the uncomplicated EVAR and FEVAR procedures was
      significant with ?13,374 for uncomplicated FEVAR and ?11,486 for complicated
      FEVAR in favor of the FEVAR group (P < 0.05). CONCLUSIONS: No financial loss was
      calculated in any of the subgroups. The costs of the endografts were the largest
      contributor to the overall costs, followed by the costs of the surgery itself and
      the stay in the ward.

PMID- 30096429
TI  - Comparison of oral microbiota in orthodontic patients and healthy individuals.
AB  - : Orthodontic treatments often include dental displacement using a fixed retainer
      such as braces, which may result in the accumulation of plaque that provides a
      suitable environment for microorganisms to cause oral infection. So, this study
      was designed to investigate the microbial diversity among orthodontic patients
      and healthy individuals. METHODS: Fifty individuals i.e. 30 orthodontic patients
      and 20 normal individuals were included in this study. Samples were collected
      during the midterm of orthodontic treatment (10-12 months). Saliva samples were
      collected and total DNA was isolated. Polymerase chain reaction denaturing
      gradient gel electrophoresis (PCR-DGGE) with universal primers targeting the V3
      region of 16s rRNA was used to study the bacterial diversity among different
      orthodontic and control groups. After DGGE profile analysis, the predominant
      product bands from the gel were excised, cloned, and sequenced to confirm the
      taxonomic identity followed by its quantification by using real-time PCR with
      gene-specific primers. RESULTS: Both orthodontic treatment and control groups
      formed two distinct clustering profiles, but the Shannon-Weaver index (H')
      indicated greater microbial diversity in the orthodontic group (P = 0.08).
      Sequence analysis and real-time PCR revealed a greater number of Pseudomonas spp.
      in the orthodontic group, while there was no significant difference in
      Streptococcal spp. CONCLUSION: This study suggested alterations in the oral
      microbiota following orthodontic treatment would provide diagnostic tools to
      identify prevalent microbes associated with oral infections that may prove useful
      for developing future therapies.

PMID- 30096430
TI  - WITHDRAWN: Paeoniflorin attenuates LPS-induced inflammation in nucleus pulposus
      cells via Nrf-2/HO-1/HMGB1/NF-kappaB pathway.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 30096431
TI  - ChIP-seq analysis reveals alteration of H3K4 trimethylation occupancy in cancer
      related genes by cold atmospheric plasma.
AB  - Cold atmospheric plasma (CAP) has gained attention for use in cancer treatment
      owing to its ability to preferentially induce cancer cell death; however, the
      involved molecular mechanism remains to be elucidated. Herein, an epigenetic
      effect of CAP on cancer cells was examined by performing a genome-wide ChIP-seq
      for H3K4me3 in MCF-7 breast cancer cell line. Consequently, 899 genes showed
      significantly changed methylation level at H3K4 with constructing "Cellular
      Compromise, DNA Replication, Recombination, Repair, and Cell Cycle" as the top
      network. Comparisons with expression array data revealed a coincidence between
      histone modification and gene expression for 18 genes, and the association was
      confirmed by ChIP-PCR and qRT-PCR for selected genes. The expression of the
      affected genes, such as HSCB and PRPS1, was recovered when a histone demethylase
      JARID1A was inhibited. Furthermore, JARID1A was induced by CAP via the reactive
      oxygen species signaling. The two genes are known as oncogenes and show a higher
      expression in breast cancer tissue, and this was supported by the decreased
      colony formation ability of MCF-7 cells when the cells were treated with siRNAs
      against each gene. Taken together, these data indicate that CAP inhibits cancer
      cell proliferation by modulating the methylation level of H3K4 corresponding to
      oncogenes.

PMID- 30096432
TI  - The autophagic response to oxidative stress in osteoarthritic chondrocytes is
      deregulated.
AB  - It has been reported that oxidative stress (OS) is involved in the pathogenesis
      of osteoarthritis (OA) and that defective autophagy is accompanying this age
      related disease. Moreover, it has been proposed that induction of autophagy could
      serve as therapeutic mean, as it was shown to alleviate several symptoms in OA
      animal models. On the contrary, it is also known that autophagic death, which
      results from over-activation of autophagy, is also a contributor in the
      development of this disease. Given this discrepancy, in this study we aimed at
      analysing the autophagic response against acute exogenous oxidative insult of
      chondrocytes from healthy individuals (control) and OA patients (OA). Cells were
      treated with sublethal concentrations of hydrogen peroxide (H2O2) and then
      allowed to recover for different periods of time. Firstly, mRNA levels of
      autophagy-related genes (ATG5, Beclin-1 and LC3) were found significantly reduced
      in OA chondrocytes compared to control chondrocytes under physiological
      conditions. After the exposure to OS, in control cells mRNA and protein levels of
      these genes initially increased and decreased back to their basal levels 6-24 h
      after treatment. On the contrary, in OA chondrocytes the levels of autophagy
      related genes remained high even 24 h post-treatment, indicating their inability
      to attenuate autophagy. Under the same conditions, the staining pattern of LC3,
      known marker of autophagosome formation, was analysed, and possible morphological
      differences between mitochondria of control and OA cells were microscopically
      assessed. These analyses revealed higher number of impaired mitochondria as well
      as increased autophagosome formation in OA cells as compared to control cells at
      all time points. Taken together, our results demonstrate a deregulation of the
      autophagic response against the oxidative insult in OA chondrocytes and offers
      insights on autophagy's role in the progression of OA.

PMID- 30096433
TI  - Mechanical stretch induces antioxidant responses and osteogenic differentiation
      in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling
      pathway.
AB  - Mesenchymal stem cells (MSCs) are promising cell sources for regenerative
      medicine. Growing evidence has indicated that mechanical stimuli are crucial for
      their lineage-specific differentiation. However, the effect of mechanical loading
      on redox balance and the intracellular antioxidant system in MSCs was unknown. In
      this study, human bone marrow-derived MSCs (BM-MSCs) were subjected to cyclic
      stretch at the magnitude of 2.5%, 5%, and 10%. Cell proliferation, intracellular
      reactive oxygen species (ROS), expression of antioxidant enzymes, and osteogenic
      differentiation were evaluated. RNA was extracted and subjected to DNA microarray
      analysis. Sirtinol and compound C were used to investigate the underlying
      mechanisms involved silent information regulator type 1 (SIRT1) and AMP-activated
      protein kinase (AMPK). Our results showed that mechanical stretch at appropriate
      magnitudes increased cell proliferation, up-regulated extracellular matrix
      organization, and down-regulated matrix disassembly. After 3 days of stretch,
      intracellular ROS in BM-MSCs were decreased but the levels of antioxidant
      enzymes, especially superoxide dismutase 1 (SOD1), were up-regulated.
      Osteogenesis was improved by 5% stretch rather than 10% stretch, as evidenced by
      increased matrix mineralization and osteogenic marker gene expression. The
      expression of SIRT1 and phosphorylation of AMPK were enhanced by mechanical
      stretch; however, inhibition of SIRT1 or AMPK abrogated the stretch-induced
      antioxidant effect on BM-MSCs and inhibited the stretch-mediated osteogenic
      differentiation. Our findings reveal that mechanical stretch induced antioxidant
      responses, attenuated intracellular ROS, and improved osteogenesis of BM-MSCs.
      The stretch-induced antioxidant effect was through activation of the AMPK-SIRT1
      signaling pathway. Our findings demonstrated that appropriate mechanical
      stimulation can improve MSC antioxidant functions and benefit bone regeneration.

PMID- 30096434
TI  - F2-isoprostanes affect macrophage migration and CSF-1 signalling.
AB  - F2-isoprostanes (F2-IsoP) are formed in vivo via free radical peroxidation of
      arachidonic acid. Enhanced oxidative stress is implicated in the development of
      atherosclerosis in humans and F2-IsoP have been detected in atherosclerotic
      plaque. Colony stimulating factor-1 (CSF-1) is essential to macrophage survival,
      proliferation and differentiation and has been detected in human atherosclerotic
      plaques. Accumulation of macrophages within the vascular wall is an important
      component of atherosclerosis but little is known about the effect of F2-IsoP on
      the migration of these cells. Our aim was to examine the effect of free and lipid
      bound 15-F2t-isoprostane (15-F2t-IsoP) on macrophage migration and investigate
      the signalling pathways involved. Mouse macrophages (cell line BAC1.2F5) were pre
      incubated with 15-F2t-IsoP (free, bound to cholesterol or monoacylglycerol or
      within oxidized phospholipid) and cell migration was assessed using chemotaxis
      towards CSF-1 in Boyden chambers. Migration was also measured using the wound
      healing assay with primary mouse bone marrow derived macrophages. We showed that
      15-F2t-IsoP dose-dependently inhibited BAC1.2F5 macrophage spreading and adhesion
      but stimulated their migration towards CSF-1, with maximum effect at 10 uM.
      Analysis of CSF-1 stimulated signalling pathways in BAC1.2F5 macrophages showed
      that phosphorylation of Akt, a key mediator of cell migration, and one of its
      regulators, the mTORC2 component, Rictor, was significantly decreased. In
      contrast, phosphorylation of the adhesion kinases, FAK and Pyk2, and the adhesion
      scaffold protein, paxillin, was enhanced after treatment with 15-F2t-IsoP. Mouse
      bone marrow macrophages were transfected with FAK or Pyk2 small interfering RNA
      (siRNA) to examine the role of FAK and Pyk2 in 15-F2t-IsoP signalling. Pyk2
      silencing inhibited 15-F2t-IsoP-induced reduction in cell area and phospho
      paxillin adhesion numbers. The size distribution of adhesions in the presence of
      15-F2t-IsoP was also affected by Pyk2 silencing and there was a trend for Pyk2
      silencing to reduce 15-F2t-IsoP-stimulated macrophage migration. These results
      demonstrate that 15-F2t-IsoP affects macrophage adhesions and migration, which
      are integral components of macrophage involvement in atherosclerosis.

PMID- 30096435
TI  - Methionine sulfoxide reductase A (MsrA) mediates the ubiquitination of 14-3-3
      protein isotypes in brain.
AB  - The methionine sulfoxide reductase (Msr) system is known for its function in
      reducing protein-methionine sulfoxide to methionine. Recently, we showed that one
      member of the Msr system, MsrA, is involved in the ubiquitination-like process in
      Archaea. Here, the mammalian MsrA is demonstrated to mediate the ubiquitination
      of the 14-3-3 zeta protein and to promote the binding of 14-3-3 proteins to alpha
      synuclein in brain. MsrA was also found to enhance the ubiquitination and
      phosphorylation of Ser129 of alpha synuclein in brain. Furthermore, we
      demonstrate that, similarly to the archaeal MsrA, the mammalian MsrA can compete
      for capturing ubiquitin using the same active site it contains for methionine
      sulfoxide binding. Based on our previous observations showing that MsrA knockout
      mice have elevated expression levels of dopamine and 14-3-3 zeta and our current
      data, we propose that MsrA-dependent 14-3-3 zeta ubiquitination affects the
      regulation of alpha synuclein degradation and dopamine synthesis in the brain.

PMID- 30096436
TI  - Protective effect of calpeptin on acrylamide-induced microtubule injury in
      sciatic nerve.
AB  - The present study aimed to investigate the protective effect and mechanism of
      calpeptin (CP) on acrylamide (ACR)-induced microtubule (MT) injury in the sciatic
      nerve of rats. All rats were divided into four groups (control, CP, ACR, and ACR
      + CP):1 ml/kg saline, 200 MUg/kg CP, 30 mg/kg ACR, and 30 mg/kg ACR plus 200
      MUg/kg CP were administered to the corresponding rats for 4 weeks through
      intraperitoneal injection. Body weight and neurobehavioral indicators were
      measured weekly and alpha-tubulin, beta-tubulin, and other concerned proteins
      were estimated by western blotting and immunohistochemistry. At 4 weeks,
      decreased body weight, increased gait scores, increased hindlimb splay, and
      decreased time of fall of ACR rats were observed compared with those of control
      rats. All these mentioned changes were restored in the ACR + CP group compared
      with the ACR group. After 4 weeks of administration, western blotting and
      immunohistochemistry revealed significant increase in the protein levels of beta
      tubulin, calpain I, calpain II, Tau, microtubule-associated protein 2 (MAP2),
      protein kinase C, and cyclin-dependent kinase 5 in the ACR group compared with
      the control group; these increases were significantly lower in the ACR + CP group
      than in the ACR group. Furthermore, histopathological examination revealed loose
      arrangement, disorganised structure, uneven density, and exfoliated perineurium
      in the ACR group, and CP administration improved these changes significantly. The
      present results suggest that CP has an intervening effect on ACR-induced MT
      injury. A possible mechanism is that calpain maintains the stability of MTs by
      regulating the metabolism of Tau and MAP2.

PMID- 30096437
TI  - Integrative transcriptome and microRNome analysis identifies dysregulated
      pathways in human Sertoli cells exposed to TCDD.
AB  - Male fertility and spermatogenesis are directly linked to the Sertoli cell's
      ability to produce factors associated with germ cell development. Sertoli cells
      express receptors for FSH and testosterone, and are the major regulators of
      spermatogenesis. Recent studies report that regulatory RNA molecules, such as
      microRNAs (miRNAs), are able to modulate testicular function during
      spermatogenesis and that their altered expression may be involved in male
      infertility. miRNAs may play a role in the response to xenobiotics that have an
      adverse consequences to health. An important group of xenobiotic organic
      compounds with toxic potential are dioxins, such as 2,3,7,8-tetrachlorodibenzo-p
      dioxin (TCDD). Experimental models of TCDD exposure in mice demonstrated that
      TCDD exposure causes low sperm count and delayed puberty. This study below
      examines the mechanism of TCDD's action in human Sertoli cells, through
      interrogating the expression profile of miRNAs and mRNAs, that enabled us to
      identify dysregulated molecular pathawys in Sertoli cell. 78 miRNAs presented
      altered expression, with positive regulation of 73 and negative regulation of 5
      miRNAs when compared to the control group. Regarding gene expression profile, 51
      genes were deregulated, of which 46 had positive regulation and 5 genes with
      negative regulation. Important pathways have been altered by the action of TCDD
      as AhR pathway, GPR68, FGF2 and LIF. This study has opened the door to new
      perspectives on the TCDD toxicity pathway as it affects Sertoli cells physiology
      that can ultimately lead to male infertility.

PMID- 30096439
TI  - Rectal Administration of Baclofen at the End of Life.

PMID- 30096438
TI  - Unintended Harm? Race Differences in the Relationship Between Advance Care
      Planning and Psychological Distress at the End of Life.
AB  - CONTEXT: Research has revealed racial disparities in advance care planning and
      intensity of end-of-life care. Studies of the relationship between advance care
      planning and sadness and anxiety at the end of life are inconclusive. OBJECTIVES:
      The objective of this study was to determine the extent to which the relationship
      between advance care planning and sadness and anxiety at the end of life differs
      by race. METHODS: This study analyzes data from 315 Medicare beneficiaries from
      the 2011-2016 National Health and Aging Trends Study. Caregiver-assessed
      sadness/anxiety at decedent's end of life was categorized as none, managed needs,
      and unmanaged needs. We used multinomial logistic regression and calculated
      relative risk and predicted probability of reporting sadness/anxiety by race and
      advance care planning status, controlling for demographic and health
      characteristics. RESULTS: Among non-Hispanic black/African-Americans who died,
      end-of-life discussions and having a health care proxy increased the predicted
      probability of caregivers reporting unmanaged needs related to sadness/anxiety by
      factors of 2.6 and 3.5, respectively (discussions: from 15% to 39%, P = 0.03;
      health care proxy: from 12% to 42%, P = 0.008). By contrast, among non-Hispanic
      white decedents, end-of-life discussions and naming a health care proxy were not
      associated with caregivers reporting unmanaged needs related to sadness/anxiety.
      CONCLUSION: Advance care planning may not work the same way for black and white
      individuals. End-of-life discussions and naming a health care proxy are
      potentially harmful to dying black patients' mental health. This finding suggests
      a need for additional research to understand why caregivers report unmanaged
      sadness/anxiety for dying black patients who engaged in advance care planning and
      increased attention to these patients' mental health at the end of life.

PMID- 30096440
TI  - Quality of Life Trends in People With and Without Cancer Referred to Volunteer
      Provided Palliative Care Services (ELSA): A Longitudinal Study.
AB  - CONTEXT: Trends in symptoms and functional ability are known toward the end of
      life, but less is understood about quality of life, particularly prospectively
      following service referral. OBJECTIVES: This study compares quality of life
      trajectories of people with and without cancer, referred to volunteer-provided
      palliative care services. METHODS: A secondary analysis of the ELSA trial (n = 85
      people with cancer and n = 72 without cancer) was performed. Quality of life data
      (WHOQOL-BREF) were collected at baseline (referral), four weeks, eight weeks, and
      12 weeks. Sociodemographic data were collected at baseline. We specified a series
      of joint models to estimate differences on quality of life trajectories between
      groups adjusting for participants who die earlier in the study. RESULTS: People
      with cancer had a significantly better quality of life at referral to the
      volunteer-provided palliative care services than those with nonmalignant disease
      despite similar demographic characteristics (Cohen d's = 0.37 to 0.45). More
      people with cancer died during the period of the study. We observed significant
      differences in quality of life physical and environmental domain trajectories
      between groups (b = -2.35, CI -4.49, -0.21, and b = -4.11, CI -6.45, -1.76).
      People with cancer experienced a greater decline in quality of life than those
      with nonmalignant disease. CONCLUSION: Referral triggers for those with and
      without cancer may be different. People with cancer can be expected to have a
      more rapid decline in quality of life from the point of service referral. This
      may indicate greater support needs, including from volunteer-provided palliative
      care services.

PMID- 30096441
TI  - An Automated Intervention Did Not Improve Adherence to Oral Oncolytic Agents
      While Managing Symptoms: Results From a Two-Arm Randomized Controlled Trial.
AB  - CONTEXT: An increasing number of oral cancer treatments require patient adherence
      and symptom self-management. OBJECTIVES: The report presents the effects of a
      medication reminder and symptom management intervention directed at patients
      initiating new oral oncolytic agents. METHODS: Patients (N = 272) were recruited
      at six comprehensive cancer centers, interviewed over the telephone after oral
      agent initiation, and randomized to either standard care or a medication reminder
      and symptom management intervention. In the intervention arm, the automated
      system called patients daily to remind them about taking their medications and
      weekly to assess 18 symptoms and refer patients to a printed Medication
      Management and Symptom Management Toolkit. Severity of 18 symptoms was also
      assessed during telephone interviews at Week 4 (midintervention), Week 8
      (postintervention), and Week 12 (follow-up). Adherence was measured using the
      relative dose intensity, the ratio of dose taken by patient out of dose
      prescribed by the oncologist, and assessed using pill counts at Weeks 4, 8, and
      12 and prescribing information from medical records. RESULTS: The relative dose
      intensity was high and did not differ by trial arm. Symptom severity was
      significantly lower (P < 0.01) in the experimental arm at Week 8 but not at Weeks
      4 or 12. CONCLUSION: Adherence may be less of a problem than originally
      anticipated, and intervention was not efficacious possibly because of already
      high rates of patient adherence to oral oncolytic medication during first 12
      weeks. Longer follow-up in future research may identify subgroups of patients who
      need interventions to sustain adherence.

PMID- 30096442
TI  - Using Routinely Collected Data to Ascertain Concordance With Advance Care
      Planning Preferences.
AB  - CONTEXT: One of the key outcomes of advance care planning is whether patients had
      received care that was consistent with their expressed goals and preferences.
      OBJECTIVES: The aims of this study were to illustrate the feasibility of using
      routinely collected health care data that include hospital procedural codes,
      diagnosis-related codes, health services utilization, and death registry data and
      to ascertain the level of concordance between care received and the stated goals.
      METHODS: In this retrospective cohort study, medical treatments were ascertained
      using a combination of hospital procedural codes and diagnosis-related codes.
      Places of care were obtained by reviewing the sequence of health services used,
      and the place of death was obtained from the national death registry. To
      ascertain concordance, medical treatment, places of care, and place of death were
      compared against the individual's preferences. RESULTS: The sample includes 1731
      decedents (aged 21 years and above) who completed their advance care planning
      documentation as part of a national program. Ninety-eight percent who wished for
      comfort measures met their preferences. Sixty-five percent of individuals who
      wished to be cared for at home received care at home. Nearly 40% of all
      individuals who opted to die at home achieved their wishes, whereas 76% of those
      who opted for home or hospital and home or hospice had their preferences
      fulfilled. CONCLUSION: Administrative data offer a cost-efficient and powerful
      method for assessing outcomes for a large population-based national program.
      However, this approach is still at an early stage of development and needs to be
      further validated before it can be used at scale.

PMID- 30096443
TI  - Do the Phenotypes of Symptom Fluctuation Differ Among Motor Subtypes in Patients
      With Delirium?
AB  - CONTEXT: Fluctuation in symptoms is a core feature of delirium. However, it is
      not well known whether the fluctuating nature would differ or not among the
      delirium subtype groups. OBJECTIVE: This study compared phenotypes of diurnal
      fluctuation among different delirium subtypes using a prospective design.
      METHODS: The motor subtypes of delirium patients were determined using the
      Delirium Motor Subtype Scale, fluctuations in consciousness levels were monitored
      with the Richmond Agitation-Sedation Scale (RASS), and symptom severity was
      assessed with the Nursing Delirium Screening Scale (Nu-DESC). All scales were
      administered at three time points over 24 hours; fluctuations in and phenotypes
      of symptoms were compared according to subtype of delirium using repeated
      measures analysis of variance after adjustment for covariates. RESULTS: This
      study included 224 delirium patients. Of this patients, 144 (64.3%) were
      classified as hyperactive, 25 (11.2%) as hypoactive, 33 (14.7%) as mixed, and 22
      (9.9%) as no subtype. Scores on the RASS and Nu-DESC significantly changed during
      the evening and/or night and there were significant subtype group * time
      interaction for the RASS and Nu-DESC (F = 9.66, P < 0.001 and F = 5.11, P <
      0.001, respectively). Post hoc analyses revealed that the hyperactive and mixed
      subtype groups had higher mean RASS scores and greater ranges of fluctuation than
      the other groups. The mixed subtype group was differentiated from hyperactive and
      hypoactive subtype groups by the range of fluctuation in psychomotor activity.
      CONCLUSIONS: The phenotypes of symptom fluctuation differed among the motor
      subtypes. These findings further support the rationale that fluctuations are a
      core feature of delirium and could differentiate delirium subtypes.

PMID- 30096444
TI  - Peptide-modified vemurafenib-loaded liposomes for targeted inhibition of melanoma
      via the skin.
AB  - Vemurafenib is a chemotherapeutic drug recently approved by the FDA to treat
      melanoma. Because the drug is usually delivered orally, the route of
      administration readily causes damage to major organs with limited antitumor
      efficacy and bioavailability. In this study, we developed a peptide-modified
      vemurafenib-loaded liposome for the targeted inhibition of subcutaneous melanoma
      via the skin. First, the peptide-modified vemurafenib-loaded liposomes (Vem-TD
      Lip) were prepared and characterized with respect to the size, shape and charge;
      the loading efficiency of vemurafenib; and the stability. Then, the intracellular
      uptake of these liposomes, their limited cytotoxicity, the selective inhibition
      of melanoma cells harboring BRAF mutations, and the liposome permeation ability
      were confirmed through in vitro experiments. Finally, the safety and antitumor
      activity of Vem-TD-Lip were evaluated in vivo. The results showed that
      transdermal delivery of Vem-TD-Lip effectively targeted and inhibited
      subcutaneous melanoma in male mice, the administration of Vem-TD-Lip through skin
      was better than that through oral administration and intravenous injection in
      terms of reducing damage to major organs and enhancing antitumor efficacy, and
      the peptide TD significantly enhanced the delivery of Vem-TD-Lip across the skin.
      This work provides a new strategy for delivering vemurafenib to target and
      inhibit subcutaneous melanoma.

PMID- 30096445
TI  - Prevalence and Profile of High-Impact Chronic Pain in the United States.
AB  - : The multidimensional nature of chronic pain is not reflected by definitions
      based solely on pain duration, resulting in high prevalence estimates limiting
      effective policy development. The newly proposed concept of high-impact chronic
      pain (HICP) incorporates both disability and pain duration to identify a more
      severely impacted portion of the chronic pain population yet remains
      uncharacterized at the population level. As such, we used the 2011 National
      Health Interview Survey (N = 15,670) to 1) assess the likelihood of disability in
      the overall chronic pain population, 2) estimate the prevalence of HICP, and 3)
      characterize the disability, health status, and health care use profile of this
      population in the United States. Overall, chronic pain, defined as pain
      experienced on most days or every day in the previous 3 months, was strongly
      associated with an increased risk of disability after controlling for other
      chronic health conditions (odds ratio = 4.43; 95% confidence interval = 3.73
      5.26), where disability was more likely in those with chronic pain than in those
      with stroke or kidney failure, among others. HICP affected 4.8% of the U.S. adult
      population, or approximately 10.6 million individuals, in 2011. The HICP
      population reported more severe pain and more mental health and cognitive
      impairments than persons with chronic pain without disability, and was also more
      likely to report worsening health, more difficulty with self-care, and greater
      health care use. HICP clearly represents a more severely impacted portion of the
      chronic pain population. Understanding this heterogeneity will contribute to
      developing more effective legislation promoting safe and cost-effective
      approaches to the prevention and treatment of chronic pain. PERSPECTIVE: HICP is
      a powerful new classification that differentiates those with debilitating chronic
      pain from those with less impactful chronic pain. By addressing the
      multidimensionality of chronic pain, this classification will improve clinical
      practice, research, and the development of effective health policy.

PMID- 30096446
TI  - Identifying and Advancing Best Practices for the Labeling and Dosing of Pediatric
      Liquid Medications: Progress and Challenges.

PMID- 30096447
TI  - Reliability and validity of PHQ-9 when administered by health workers for
      depression screening among women in primary care.
AB  - BACKGROUND: Depression is twice more prevalent among women but remains
      unidentified in primary care. OBJECTIVE: We aimed to estimate the reliability and
      validity of PHQ-9, when administered by health workers, a cadre of public health
      staff, posted in primary health centres. We translated PHQ-9 to Malayalam, a
      language spoken by 30 million people in Kerala, India. Health workers
      administered PHQ-9 to women (n = 238) aged 18-60 years in a high prevalent
      primary care setting. Mini International Neuropsychiatric Interview (MINI) was
      administered by the psychiatrist on the same day to diagnose depressive disorder.
      Two health workers administered PHQ-9, independently, in a subset of 21 women.
      RESULTS: The internal consistency reliability (Cronbach's alpha 0.89) and inter
      rater reliability (intra class correlation coefficient, 0.94; 95% CI, 0.86-0.95)
      were high. On ROC analysis, area under curve was 0.92 (95% CI 0.88-0.96). For a
      cut-off score of >=9, PHQ-9 had a sensitivity of 82.5%, (95% CI, 72.4-92.6),
      specificity of 90.1% (95% CI, 84.5-95.6%), positive predictive value of 73.4%
      (95% CI, 62.4-84.4%) and negative predictive value of 93.9% (95% CI, 90.2-97.6%).
      The accuracy was 88.2% (84.0-92.4%) and positive likelihood ratio was 8.3. Factor
      analysis supported a single factor, with eigen value above 1, with high loading
      for all items (0.73-0.79), except item related to appetite (0.58). This explained
      62% of variance in the data. Prevalence of MINI diagnosed depressive disorders
      was 25%. CONCLUSION: When administered by health workers, PHQ-9 has good
      reliability and at cut off score >=9, it has good validity to identify depression
      in primary care.

PMID- 30096448
TI  - Imagine squeezing a cactus: Cortical activation during affective motor imagery
      measured by functional near-infrared spectroscopy.
AB  - The activation of different brain areas during kinaesthetic and visual motor
      imagery has been extensively studied, whereas little is known about affective
      motor imagery, i.e. the imagery of pleasant/unpleasant movements. In the present
      neuroimaging study we investigated cortical activation of kinaesthetic motor
      imagery (KMI) based on emotional stimulus content by means of functional near
      infrared spectroscopy (fNIRS). Twenty healthy adult participants were instructed
      to imagine affective, and neutral motor tasks while multichannel fNIRS was
      recorded simultaneously. In the affective MI condition they had to imagine e.g.
      squeezing a cactus with their right hand several times, eliciting an unpleasant
      emotion. In the neutral condition their task was to imagine squeezing a ball.
      Significant differences in oxy-hemoglobin [oxy-Hb] concentration changes during
      KMI including affective objects in different brain regions were found.
      Specifically activation in left parietal and frontal regions was increased during
      the imagery of squeezing a cactus which induced a painful feeling. Both areas are
      also involved in the perception of pain and commonly labelled as parts of the
      "pain matrix". Our study provides novel insights in cortical activation patterns
      during affective motor imagery and its psychological and cognitive mechanisms
      underlying pain experience.

PMID- 30096449
TI  - Wildlife warning reflectors do not mitigate wildlife-vehicle collisions on roads.
AB  - Wildlife-vehicle collisions cause human fatalities and enormous economic and
      ecological losses on roads worldwide. A variety of mitigation measures have been
      developed over the past decades to separate traffic and wildlife, warn humans, or
      prevent wildlife from entering a road while vehicles are passing by, but only few
      are economical enough to be applied comprehensively. One such measure, wildlife
      warning reflectors, has been implemented over the past five decades. However,
      their efficacy is questioned because of contradictory study results and the
      variety of applied study designs and reflector models. We used a prospective,
      randomized non-superiority cross-over study design to test our hypothesis of the
      inefficacy of modern wildlife warning reflectors. We analyzed wildlife-vehicle
      collisions on 151 testing sites of approximately 2 km in length each. During the
      24-month study period, 1984 wildlife-vehicle collisions were recorded.
      Confirmatory primary and exploratory secondary analyses using a log-link Poisson
      mixed model with normal nested random intercepts of observation year in road
      segment, involved species, and variables of the road segment and the surrounding
      environment showed that reflectors did not lower the number of wildlife-vehicle
      collisions by a relevant amount. In addition, variables of the road segment and
      the surrounding environment did not indicate differential effects of wildlife
      warning reflectors. Based on our results, we conclude that wildlife warning
      reflectors are not an effective tool for mitigating wildlife-vehicle collisions
      on roads.

PMID- 30096450
TI  - Bike lanes next to on-street parallel parking.
AB  - For decades it has been the conventional wisdom that crashes involving bicyclists
      and opening car doors are rare. This belief is based on motor vehicle crash
      reports, but these reports generally exclude this crash type by definition. More
      complete sources show that dooring crashes are one of the most common causes of
      urban bicycle-motor vehicle collisions, accounting for 12%-27% of the total. This
      paper reviews all available studies of bicyclist position in bike lanes adjacent
      to on-street parking. With bike lanes meeting current minimum standards, almost
      all bicyclists were observed riding within range of opening doors. However, when
      an additional three or four feet is provided between the bike lane and parked
      cars, hardly any bicyclists are observed in the door zone. All of the design
      guides recently developed in North America for separated bike lanes include a
      buffer to account for the door zone when the bike lane is placed between on
      street parallel parking and the curb. However, only the Ontario design guide has
      a similar requirement for standard bike lanes. The buffer requirement for
      standard bike lanes adjacent to on-street parking should be incorporated into all
      design guidance. When there is not room for this necessary buffer, an alternative
      is to place a shared lane marking in the center of the travel lane, which
      encourages bicyclists to ride outside the door zone. Increasing the number of
      bicyclists who ride outside of the door zone may require lowering speed limits
      and repealing laws that create a presumption that bicyclists must always keep to
      the right of the travel lane.

PMID- 30096451
TI  - An experimental test of the impact of adolescent anxiety on parental sick role
      reinforcement behavior.
AB  - A large body of work links parental sick role reinforcement behavior to
      adolescent panic vulnerability. To date, however, little work has examined the
      role of the adolescent in this process. The current study addressed this gap in
      the literature, using a novel method to experimentally test the impact of
      adolescent anxiety during a straw-breathing task on parental propensity to engage
      in sick role reinforcement behavior. An unselected sample of 51 early adolescents
      (26 female, 10-14 years) and their parents participated in the study. Adolescents
      were trained to mimic a straw-breathing task, and adolescent reactions to the
      task were scripted. Parents were randomly assigned to watch their adolescent
      react either a) anxiously or b) non-anxiously to the straw-breathing task.
      Parents who viewed their adolescent react anxiously ended the task earlier,
      reported that they would reinforce more sick role behavior, and reported more
      negatively valenced reactions during the task than parents who viewed their
      adolescent react non-anxiously to the task. No group differences emerged in terms
      of parental self-reported or physiological arousal during the task. Results
      suggest that adolescent anxiety increases parental sick role reinforcement
      behavior. Findings are discussed in terms of future directions for reducing
      parenting behaviors thought to increase vulnerability for panic among
      adolescents.

PMID- 30096452
TI  - Purified sulforaphane from broccoli (Brassica oleracea var. italica) leads to
      alterations of CDX1 and CDX2 expression and changes in miR-9 and miR-326 levels
      in human gastric cancer cells.
AB  - BACKGROUND: Genetic alterations and epigenetic modifications are two main factors
      involved in gastric carcinogenesis, progression, and metastasis. Several miRNAs
      such as miRNA-9 and miRNA-326 may play important role in gastric cancer by
      targeting the 3'UTR of the caudal type homeobox (CDX) 1 and 2 mRNA respectively.
      The use of herbal medicines has been widely considered in the treatment of
      cancers such as gastric cancer. Sulforaphane extracted from broccoli may
      indirectly prevent cancer through affecting different signaling pathways. The aim
      of this study was to evaluate the effect of different concentrations of
      sulforaphane extracted from broccoli sprout (SEBS) on viability, death pattern,
      and expression alterations of CDX1/2 as well as miRNA-9 and miRNA-326 in normal
      (HF2FF) and gastric cancer cell lines. METHODS: Two gastric cancer cell lines
      (AGS and MKN45) and HF2FF normal cell line were cultured and treated with
      different concentrations (31.25, 62.5, 125, and 250 MUg/ml) of the purified
      sulforaphane. Expression levels of CDX1 and CDX2 as well as miRNA-9 and miRNA
      326, and mechanisms leading to cell death were assessed by Taqman real time PCR
      assay and flow cytometry, respectively. RESULTS: Significant dose-dependent and
      anti-proliferative effects of the SEBS were observed on AGS and MKN45 cells after
      48 h with an IC50 value of about 112 and 125 MUg/ml, respectively (P < 0.001).
      Apoptotic cells were observed in AGS and MKN45 cells but not HF2FF after 48 h of
      treatment with SEBS. Furthermore, significant changes in expression of CDX1,
      CDX2, miR-9 and miR-326 in the gastric cancer lines (AGS and MKN45), were
      observed under different concentrations of SEBS. CONCLUSION: Our present study
      suggests that the SEBS may influence gastric cancer cell lines at specific doses
      and change their proliferation rate by altering the expression of CDX1, CDX2, miR
      9, and miR-326.

PMID- 30096453
TI  - Genetic variants within 17q12 are associated with the risk of cervical cancer in
      the Han Chinese population.
AB  - Chromosome 4q12 and 17q12 have been identified as two regions associated with
      susceptibility to cervical cancer in a genome-wide association study. To identify
      potential causal variants within these two regions, we conducted a case-control
      study including 1486 patients with cervical cancer and 1536 age-matched (+/-5
      years) healthy controls. Based on RegulomeDB database, 12 potentially functional
      variants were selected and then genotyped by using Sequenom MassARRAY. Univariate
      and multivariate logistic regression models were used to evaluate the
      associations. We found that the G allele of rs8076131 and the A allele of
      rs12150079 in 17q12 region were significantly associated with increased risk of
      cervical cancer (adjusted OR = 1.15, 95% CI = 1.02-1.30, P = 0.02 for rs8076131;
      adjusted OR = 1.19, 95% CI = 1.03-1.36, P = 0.02 for rs12150079). Individuals
      with 3-4 risk alleles of these two variants had 24% higher odds of cervical
      cancer than those without the risk alleles (OR = 1.24, 95% CI = 1.07-1.44, P <
      0.01). The stratified analysis showed that the associations of rs8076131 and
      rs12150079 with cervical cancer risk were statistically significant in subgroups
      of older menarche age (>16 years), more parities (>=2), nonsmokers, and having no
      family cancer history, but the test results for subgroup heterogeneity were not
      significant. The current study provides the evidence that rs8076131 and
      rs12150079 in 17q12 region may contribute to cervical cancer susceptibility in
      the Han Chinese population.

PMID- 30096454
TI  - Identification of NMU as a potential gene conferring alectinib resistance in non
      small cell lung cancer based on bioinformatics analyses.
AB  - Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, and
      adjuvant targeted therapy has shown great benefits for the NSCLC patients with
      specific genomic mutations. Alectinib, a selective anaplastic lymphoma kinase
      (ALK) inhibitor, has been clinically used for the NSCLC patients with ALK
      rearrangement, however, irreversible therapeutic resistance for the patients
      receiving alectinib treatment frequently occurs. Here we show that neuromedin U
      (NMU) may confer the alectinib resistance in NSCLC via multiple mechanisms based
      on the integrative bioinformatics analyses. Through employing the bioinformatics
      analyses of three microarray datasets, NMU, overexpressed in both NSCLC tissues
      and alectinib-resistant NSCLC cells, was initially identified as potential
      candidate for causing alectinib resistance in NSCLC. The resistance function of
      NMU in NSCLC was validated by performing protein/gene interactions and biological
      process annotation analyses, and further validated by analyzing the transcription
      factors targeting NMU mRNA. Collectively, these results indicated that NMU may
      confer alectinib resistance in NSCLC.

PMID- 30096455
TI  - Genome-wide identification of FK506-binding domain protein gene family, its
      characterization, and expression analysis in tomato (Solanum lycopersicum L.).
AB  - FK506-protein also called FKBP protein belongs to PPIase (peptidylprolylcis-trans
      isomerase) super family of immune suppressive drugs that act as molecular protein
      chaperones. In plants, FKBPs are ubiquitous and involved in various biological
      and physiological processes like plant germination, development, stress response
      and hormonal signaling. Here, we identified 24 FKBP family genes in tomato by
      using different tools and bioinformatic approaches. The specific structure,
      domain organisation, cis-regulatory elements, phylogenetic analysis, multiple
      sequence alignment, tissue-specific expression patterns and expression under
      abiotic and phytohormone stresses of all genes were investigated. The genes are
      clustered on ten tomato chromosomes and are categorised into two sub-classes;
      single and multiple domains protein gene. One of the main features of tomato
      FKBPs is their large fractions localized in chloroplast (in silico analysis) and
      clustered together phylogenetically. Tissue-specific expression analysis using
      available RNA-seq data revealed the spatiotemporal expression of the FKBPs, but
      few genes were observed with relatively high expressions in certain developmental
      stages. However, the quantitative expression profile of all genes under hormone
      stress provided a supporting evidence for their potential role in hormone signal
      pathways. Our prediction not only providing the foundation for better
      understanding the complex physiological regulation of FKBP gene family in tomato
      but also providing the potential aids to accelerate tolerance and survival in
      tomato under stressful condition.

PMID- 30096456
TI  - CRISPLD1 rs12115090 polymorphisms alters antiplatelet potency of clopidogrel in
      coronary artery disease patients in Chinese Han.
AB  - BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is a
      recommended treatment for coronary artery disease (CAD) patients undergoing
      percutaneous coronary intervention (PCI) to reduce the rate of ischemic events
      and stent thrombosis. However, high on-treatment platelet reactivity (HTPR)
      during clopidogrel therapy for some patients may lead to outcome failure and
      occurrence of cardiovascular events. Amounts of studies have proved that genetic
      factors may contribute to HTPR. In our study, we explored the predictive value of
      10 single nucleotide polymorphisms (SNPs) in 8 genes indicated by exome
      sequencing with clopidogrel efficacy. METHODS: Two hundred and forty-one Han
      Chinese CAD patients (mean age: 61 +/- 10 years) receiving dual antiplatelet
      therapy were recruited, among which 118 patients administered with 300 mg loading
      dose (LD) clopidogrel for 12-24 h and 123 subjects administered with 75 mg/day
      maintain dose (MD) clopidogrel for at least 5 days before discharge. The platelet
      reaction index (PRI) was determined to reflect clopidogrel response in the
      patients. Venous blood samples were drawn from all participants to extract
      genomic DNA. MassARRAY, Sanger sequencing and polymerase chain reaction
      restriction fragment length polymorphism (PCR-RFLP) were used to determine the
      genotypes of 10 SNPs. RESULTS: Allelic tests showed significant differences in
      genotype distribution between HTPR and normal on-treatment platelet reactivity
      (NTPR) patients for 3 SNPs including CYP2C19 rs4244285 (CYP2C19*2) (co-dominant
      model: p = 0.003, dominant model: p = 0.004, recessive model: p = 0.012),
      CRISPLD1 rs12115090 (co-dominant model: p = 0.011, dominant model: p = 0.004),
      and LTA4H rs11108379 (dominant model: p = 0.041). After adjusting for covariates
      including clinical characteristics of patients, concomitant medications and
      complications, we confirmed that carriers of the CYP2C19*2 showed significantly
      increased risk of HTPR (*2/*2 vs *1/*1: OR = 12.266, 95% CI: 1.336-112.592, p =
      0.027; *1/*2 + *2/*2 vs *1/*1: OR = 2.202, 95% CI: 1.083-4.480, p = 0.029).
      Contrarily, carriers of the CRISPLD1 rs12115090 C allele showed significantly
      reduced risk of HTPR (CC vs AA: OR = 0.242, 95% CI: 0.078-0.752, p = 0.014; CA +
      CC vs AA: OR = 0.457, 95% CI: 0.232-0.904, p = 0.024) in Chinese CAD patients. In
      addition, carriers of the CYP2C19*2 allele showed significantly increased PRI
      (*1/*2 vs *1/*1: p = 0.008, 2/*2 vs 1/*1: p < 0.001, *2/*2 vs 1/*2: p = 0.011),
      while patients carrying the rs12115090 C allele showed significantly decreased
      PRI than the wild-type AA homozygotes (CA vs AA: p = 0.046, CA + CC vs AA: p =
      0.023). CONCLUSION: CYP2C19*2 reduced the antiplatelet potency of clopidogrel and
      increased the risk of HTPR, while CRISPLD1 rs12115090 A>C polymorphism increased
      the antiplatelet potency of clopidogrel. Genetic tests, especially for CYP2C19*2
      are recommended in Han Chinese CAD patients before using of clopidogrel.

PMID- 30096457
TI  - Comparative transcriptome analysis of genes involved in Na+ transport in the
      leaves of halophyte Halogeton glomeratus.
AB  - Compartmentalization of Na+ into vacuoles is considered to be the most critical
      aspect of salt tolerance in H. glomeratus, an annual, succulent halophyte.
      Previous analysis of transcriptome involved in the H. glomeratus salt stress
      response relied on next-generation sequencing technologies that limit the capture
      of accurately spliced, full-length isoforms. To gain deeper insights into its
      salt stress response, we used the H. glomeratus Iso-Seq transcriptome database as
      a reference, and subsequent next-generation sequencing was subjected to various
      NaCl concentrations of leaves from plants revealed 115 upregulated and 87
      downregulated differentially expressed isoforms (core DEIs). The majority of the
      core DEIs were involved in carbohydrate metabolism and energy production and
      conversion. In contrast, levels of known isoforms encoding Na+ transporters did
      not change significantly under salt stress. However, 16 core DEIs of unknown
      function were predicted to possess transmembrane domains, suggesting that these
      candidate isoforms could be involved in Na+ transport in H. glomeratus. These
      results suggest a potential means for identification of novel Na+ transporters,
      in addition to providing a foundation for further investigation of Na+ transport
      networks in halophytes.

PMID- 30096458
TI  - BMI1 and PTEN are key determinants of breast cancer therapy: A plausible
      therapeutic target in breast cancer.
AB  - BMI-1 (B-lymphoma Mo-MLV insertion region 1) is a key protein partner in polycomb
      repressive complex 1 (PRC1) that helps in maintaining the integrity of the
      complex. It is also a key player in ubiquitination of histone H2A which affects
      gene expression pattern involved in various cellular processes such as cell
      proliferation, growth, DNA repair, apoptosis and senescence. In many cancers,
      Overexpression of BMI1correlates with advanced stages of disease, aggressive
      clinicopathological behavior, poor prognosis resistance to radiation and
      chemotherapy. BMI1 is emerging as a key player in EMT, chemo-resistance and
      cancer stemness. Overexpression is observed in various cancer types such as
      breast, primary hepatocellular carcinoma (HCC), gastric, ovarian, head and neck,
      pancreatic and lung cancer. Studies have shown that experimental reduction of BMI
      protein level in tumor cells results in inhibition of cell proliferation,
      induction of apoptosis and/or senescence, and increases susceptibility to
      cytotoxic agents and radiation therapy. Thus, inhibition of BMI1 expression
      particularly in breast cancer stem cells can be used as a potential strategy for
      the complete elimination of tumor and to prevent disease relapse. On other hand
      PTEN is known to be an important tumor suppressor next to p53. In many cancers
      particularly in breast cancer, p53 and PTEN undergo mutations. Studies have
      indicated the functional and mechanistic link between the BMI-1oncoprotein and
      tumor suppressor PTEN in the development and progression of cancer. The current
      review focuses on recent findings of how oncogenicity and chemo-resistance are
      caused by BMI1. It also highlights the transcriptional regulation between BMI1
      and PTEN that dictates the therapeutic outcome in cancers where the functional
      p53 is absent. Herein, we have clearly demonstrated the regulation of
      transcription at genomic loci of BMI1 and PTEN in cancerous tissue or cells and
      the possible epigenetic regulation by histone deacetylase inhibitors (HDACi) at
      BMI1 and PTEN loci that may provide some clue for the possible therapy against
      TNBC in near future.

PMID- 30096459
TI  - Transcriptional activation of a chimeric retrogene PIPSL in a hominoid ancestor.
AB  - Retrogenes are a class of functional genes derived from the mRNA of various
      intron-containing genes. PIPSL was created through a unique mechanism, whereby
      distinct genes were assembled at the RNA level, and the resulting chimera was
      then reverse transcribed and integrated into the genome by the L1
      retrotransposon. Expression of PIPSL RNA via its transcription start sites (TSSs)
      has been confirmed in the testes of humans and chimpanzee. Here, we demonstrated
      that PIPSL RNA is expressed in the testis of the white-handed gibbon. The 5'-end
      positions of gibbon RNAs were confined to a narrow range upstream of the PIPSL
      start codon and overlapped with those of orangutan and human, suggesting that
      PIPSL TSSs are similar among hominoid species. Reporter assays using a luciferase
      gene and the flanking sequences of human PIPSL showed that an upstream sequence
      exhibits weak promoter activity in human cells. Our findings suggest that PIPSL
      might have acquired a promoter at an early stage of hominoid evolution before the
      divergence of gibbons and ultimately retained similar TSSs in all of the
      lineages. Moreover, the upstream sequence derived from the phosphatidylinositol-4
      phosphate 5-kinase, type I, alpha 5' untranslated region and/or neighboring
      repetitive sequences in the genome possibly exhibits promoter activity.
      Furthermore, we observed that a TATA-box-like sequence has emerged by nucleotide
      substitution in a lineage leading to humans, with this possibly responsible for a
      broader distribution of the human PIPSL TSSs.

PMID- 30096461
TI  - Beyond structures of highly symmetric purified viral capsids by cryo-EM.
AB  - Cryogenic transmission electron microscopy (cryo-EM) is widely used to determine
      high-resolution structures of symmetric virus capsids. The method holds promise
      for extending studies beyond purified capsids and their symmetric protein shells.
      The non-symmetric genome component has been addressed in dsRNA cypoviruses and
      ssRNA bacteriophages Qbeta and MS2. The structure of human herpes simplex virus
      type 1 capsids has been determined within intact virions to resolve capsid
      tegument interactions. Electron tomography under cryogenic conditions (cryo-ET),
      has allowed resolving an early membrane fusion intermediate of Rift Valley fever
      virus. Antibody-affinity based sample grids allow capturing of virions directly
      from cell cultures or even clinical samples. These and other emerging methods
      will support studies to address viral entry, assembly and neutralization
      processes at increasingly high resolutions and native conditions.

PMID- 30096460
TI  - A comparison of four different imaging modalities - Conventional, cross
      polarized, infra-red and ultra-violet in the assessment of childhood bruising.
AB  - BACKGROUND: It is standard practice to image concerning bruises in children. We
      aim to compare the clarity and measurements of bruises using cross polarized,
      infra-red (IR) and ultra-violet (UV) images to conventional images. METHODS:
      Children aged <11 years with incidental bruising were recruited. Demographics,
      skin and bruise details were recorded. Bruises were imaged by standard protocols
      in conventional, cross-polarized, IR and UV lights. Bruises were assessed in vivo
      for contrast, uniformity and diffuseness, and these characteristics were then
      compared across image modalities. Color images (conventional, cross polarized)
      were segmented and measured by ImageJ. Bruises of grey scale images (IR, UV) were
      measured by a 'plug in' of ImageJ. The maximum and minimum Feret's diameter, area
      and aspect ratio, were determined. Comparison of measurements across imaging
      modalities was conducted using Wilcoxon rank sum tests and modified Bland-Altman
      graphs. Significance was set at p < 0.05. RESULTS: Twenty five children had 39
      bruises. Bruises that were of low contrast, i.e. difficult to distinguish from
      surrounding skin, were also more diffuse, and less uniformity in vivo. Low
      contrast bruises were best seen on conventional and cross-polarized images and
      less distinctive on IR and UV images. Of the 19 bruises visible in all
      modalities, the only significant difference was maximum and minimum Feret's
      diameters and area were smaller on IR compared to conventional images. Aspect
      ratios were not affected by the modality. CONCLUSIONS: Conventional and cross
      polarized imaging provides the most consistent bruise measurement, particularly
      in bruises that are not easily distinguished from surrounding skin visually.

PMID- 30096462
TI  - Evaluation of malaria multiplex/nested PCR performance at low parasite densities
      and mixed infection in Iran: A country close to malaria elimination.
AB  - BACKGROUND: Malaria is still a major public health problem in subtropical and
      tropical regions. The rapid and accurate diagnosis of malaria remains a challenge
      in most of the endemic areas. The primary objective of the present study was to
      evaluate the performance of multiplex/nested PCR in detecting Plasmodium
      falciparum at low parasite densities and mixed infection. METHODS: The study was
      performed in the Sistan-Baluchestan province of the southeastern Iran, from May
      2015 to July 2016. A total of 105 patients suspected to malaria infection were
      enrolled in the study. The obtained DNA products, extracted from the thick/thin
      films, were analyzed by multiplex/nested PCR using genus-specific primers and
      compared with light microscopy. RESULTS: 43 samples were confirmed to be infected
      by microscopic examination. Among 43 microscopically diagnosed P. falciparum
      cases, 11.4% (12/105) were confirmed by multiplex/nested PCR, 36.2% (38/105) were
      confirmed as P. vivax, 1.9% (2/105) had mixed infections with P. falciparum and
      P. vivax. Among microscopy-negative samples, 10 samples turned malaria-positive
      in nPCR. In multiplex/nested PCR, the rate of mixed infections was 8.6% (9/105).
      When compared to LM, the sensitivity, specificity, positive predictive value and
      negative predictive value of multiplex/nested PCR were calculated to be 82.8,
      91.5, 92.3 and 81.1%, respectively. CONCLUSION: In this study, we showed that
      microscopic examination of blood smears does not reliably distinguish Plasmodium
      species in the case of mixed infections. Therefore, it seems that
      multiplex/nested PCR is a good candidate for examining the presence of malaria
      parasites in clinically suspected but microscopically negative cases.

PMID- 30096463
TI  - Assessment of oxidant-antioxidant status alterations with tumor biomarkers and
      reproductive system hormones in uterine MYOMAS.
AB  - OBJECTIVES: Uterine myomas (UM) are responsible for significant morbidity and
      have adverse effects on quality of life in women. Reactive oxygen species (ROS)
      and antioxidant enzymes (AOE), as well as sex steroids play important roles in
      the reproductive physiology processes. Thus, we aimed to investigate the role of
      oxidant-antioxidant status in UM by measuring the AOE activities and lipid
      peroxidation (LPO) levels. This is the first study assessing these parameters
      together in UM based on also menopausal status and evaluating possible
      correlations between AOE activities, LPO markers, tumor biomarkers, female
      reproductive system hormone levels, comprehensively. STUDY DESIGN: The study
      group consisted of patients who have undergone surgical resection with confirmed
      pathology of uterine myoma (UM, n = 25) and divided into subgroups; premenopausal
      (UMpre) and postmenopausal (UMpost). Erythrocyte copper-zinc superoxide dismutase
      (Cu,Zn-SOD), catalase (CAT), glutathione peroxidase (GPx1) activities were
      measured along with plasma malondialdehyde (MDA) and urinary 8-epi-prostaglandin
      F2alpha (8-epi-PGF2alpha) levels in patients with UM. The obtained data were
      compared to the data of healthy individuals (C, n = 25) and its subgroups;
      premenopausal (Cpre) and postmenopausal (Cpost). RESULTS: All AOE activities were
      higher (~40% for Cu,Zn-SOD, p = 0.003; ~55% for CAT, p = 0.001; ~15% for GPx1, p
      = 0.169) and the LPO levels were lower (~60% for MDA, p = 0.011 and ~45% for 8
      epi-PGF2alpha, p = 0.055) in patients with UM vs control. Approximately similar
      alterations were observed in UMpre vs Cpre and in UMpost vs Cpost. A significant
      negative correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels
      (r = -0.431, p = 0.005) was reported. CONCLUSION: Decreased LPO levels might be
      the consequence of compensator high antioxidant enzyme activities against mild
      oxidative stress in the circulation of patients with UM. The marked negative
      correlation between erythrocyte Cu,Zn-SOD activity and plasma MDA levels also
      supported this finding.

PMID- 30096464
TI  - Prevalence of vitamin D deficiency in infertile women with polycystic ovarian
      syndrome and its association with metabolic syndrome - A prospective
      observational study.
AB  - OBJECTIVE: The main purpose of this study was to determine the prevalence of
      vitamin D deficiency in infertile women with polycystic ovarian syndrome (PCOS)
      and to explore the association of hypovitaminosis D with metabolic syndrome in
      women with PCOS. STUDY DESIGN: A prospective observational study was conducted in
      a tertiary care, infertility centre from March 2016 to March 2017. The primary
      outcome was estimation of the prevalence of vitamin D deficiency in infertile
      PCOS women. Secondary outcomes were to study the association of hypovitaminosis D
      with metabolic syndrome, obesity and hypercholesterolemia in PCOS patients.
      RESULTS: A total of 256 infertile women with PCOS were included in the study.
      Vitamin D deficiency was observed in 70.3% women, 20.3% were vitamin D
      insufficient and only 9.4% were vitamin D sufficient. Metabolic syndrome was seen
      in 80/256 (31.25%) women. There was no evidence of an association between
      hypovitaminosis D and metabolic syndrome, obesity or hyperlipidemia. There was a
      strong evidence of an association between waist circumference of >80 cm and
      vitamin D deficiency (p = 0.02). CONCLUSION: Vitamin D deficiency is highly
      prevalent in infertile PCOS women and there seems to be no association between
      hypovitaminosis D and the metabolic syndrome in the same population.

PMID- 30096465
TI  - Pregnancy outcome in Turner syndrome: A French multi-center study after the 2009
      guidelines.
AB  - OBJECTIVE: This study aimed to assess the application of the French guidelines
      for pregnancies in Turner syndrome (TS) and their impact on perinatal prognosis.
      STUDY DESIGN: We performed a French multi-center retrospective study (14
      centers), including TS pregnant patients (spontaneously or by Assisted
      Reproductive Technology (ART)) between January 2006 and July 2017. Only clinical
      pregnancies were analyzed. The adjustment of medical follow-up modalities to
      French guidelines was evaluated for all pregnancies after 2009. Pregnancies from
      oocyte donation (OD) after 2009 were compared to those of a cohort of TS
      pregnancies obtained by OD before 2009, which were reported by the French Study
      Group for Oocyte Donation. RESULTS: One hundred seventy pregnancies in 103
      patients were included: 35 spontaneous, 5 by means of intra-conjugal ART, and 130
      with OD. No serious maternal complications were observed. We reported two
      stillbirths and one intra uterine fetal death. The French guidelines were
      partially respected. The preconceptional assessment was carried out in 74% of
      cases. Cardiology follow-up during pregnancy was performed in accordance with
      guidelines in 74% of patients. Postpartum cardiac ultrasonography was performed
      in 45% of pregnancies but only in 11% within 8 days post-partum. When compared to
      the 2009 historical cohort, the rates of high blood pressure (19% vs. 38%; p <
      0.005) pre-eclampsia (8% vs. 21%; p < 0.005) and prematurity <35 weeks (15% vs
      38%; p < 0.0001) were lower. CONCLUSIONS: The implementation of guidelines has
      allowed the standardization of TS pregnancy care and improved perinatal
      indicators for both mothers and children. However, an effort must be done, in a
      postpartum survey.

PMID- 30096466
TI  - The temporal effect of Category II fetal monitoring on neonatal outcomes.
AB  - OBJECTIVE: To correlate the duration of Category II cardiotocograms (CTG) with
      adverse neonatal outcomes associated with perinatal asphyxia and determine the
      duration before fetal compromise. STUDY DESIGN: This retrospective, observational
      study used electronic medical record data from a cohort of 271 patients,
      delivered by C-section due to non-reassuring fetal heart rate, at a tertiary
      medical center, from 2015 through 2017. Duration of Category II CTG, variability,
      tachycardia and deceleration frequency were analyzed and correlated to immediate
      postnatal outcomes. including cord pH <= 7, cord base excess >12, 1- and 5-min
      Apgar scores <=7, need for ventilation, need for chest compressions, NICU
      admission, hypoglycemia and convulsions. Intrapartum fever and meconium stained
      amniotic fluid were correlated to the same outcomes. Categorical and continuous
      variables were analyzed using chi-square and t-tests, respectively. P < 0.05 was
      considered significant. RESULTS: The mean duration of Category II CTG was 146 min
      (range 17-553). Longer duration did not result in increased rates of adverse
      neonatal outcomes. In contrast, reduced fetal heart rate (FHR) variability, fetal
      tachycardia and intrapartum fever did show increased rates of adverse neonatal
      outcomes, as follows: patients exhibiting reduced vs. normal (FHR) variability
      had 12.9% vs. 1.4% cord pH <= 7, P = 0.006 and 12.5% vs. 1.3% cord BE > 12, P =
      0.004: patients with fetal tachycardia vs. normal baseline FHR exhibited 48% vs.
      17.9% 1-minute Apgar score <=7, P = 0.0004; 8% vs. 0.8% 5-minute Apgar score <=7,
      P = 0.04; and 48% vs. 18.7% ventilation support, P < 0.001; patients with
      intrapartum fever vs. normal temperature, cord BE > 12 was seen in 9.7% vs. 1.7%,
      P = 0.035; 1-minute Apgar score was <=7 in 35.5% vs. 18.7%, P = 0.03; 5-minute
      Apgar score <=7 in 9.7% vs. 0.4%, P = 0.005; need for ventilation in 35.5% vs.
      19.6%, P = 0.042; need for chest compressions in 6.45% vs. none, P = 0.013; and
      NICU admission in 12.9% vs. 2.5%, P = 0.018. CONCLUSIONS: Our results suggest
      that the duration of Category II CTG alone does not appear to predict perinatal
      asphyxia. Parameters associated with perinatal asphyxia are reduced FHR
      variability, fetal tachycardia and intrapartum fever. Therefore, when
      contemplating intervention during labor to avoid fetal asphyxia, these parameters
      should be strongly considered.

PMID- 30096467
TI  - Letter to Editor: F.S. Kaplan, et al., Early clinical observations on the use of
      imatinibmesylate in FOP: A report of seven cases, Bone (2017).

PMID- 30096468
TI  - Marked alterations in the structure, dynamics and maturation of growth plate
      likely explain growth retardation and bone deformities of young Hyp mice.
AB  - Mechanisms underlying growth impairment and bone deformities in X-linked
      hypophosphatemia are not fully understood. We here describe marked alterations in
      the structure, dynamics and maturation of growth plate in growth-retarded young
      Hyp mice, in comparison with wild type mice. Hyp mice exhibited reduced
      proliferation and apoptosis rates of chondrocytes as well as severe disturbance
      in the process of chondrocyte hypertrophy disclosed by abnormal expression of
      proteins likely involved in cell enlargement, irregular chondro-osseous junction
      and disordered bone trabecular pattern and vascular invasion in the primary
      spongiosa. (Hyp mice had elevated circulating FGF23 levels and over activation of
      ERK in the growth plate.) All these findings provide a basis to explain growth
      impairment and metaphyseal deformities in XLH. Hyp mice were compared with wild
      type mice serum parameters, nutritional status and growth impairment by
      evaluation of growth cartilage and bone structures. Hyp mice presented
      hyphosphatemia with high FGF23 levels. Weight gain and longitudinal growth
      resulted reduced in them with numerous skeletal abnormalities at cortical bone.
      It was also observed aberrant trabecular organization at primary spongiosa and
      atypical growth plate organization with abnormal proliferation and hypertrophy of
      chondrocytes and diminished apoptosis and vascular invasion processes. The
      present results show for the first time the abnormalities present in the growth
      plate of young Hyp mice and suggest that both cartilage and bone alterations may
      be involved in the growth impairment and the long bone deformities of XLH.

PMID- 30096469
TI  - Factors associated with proximal femur fracture determined in a large cadaveric
      cohort.
AB  - Many researchers have used cadaveric fracture tests to determine the relationship
      between proximal femur (hip) fracture strength and a multitude of possible
      explanatory variables, typically considered one or two at a time. These variables
      include subject-specific proximal femur variables such as femoral neck areal bone
      mineral density (aBMD), sex, age, and geometry, as well as physiological hip
      fracture event variables such as fall speed and angle of impact. However, to our
      knowledge, no study has included all of these variables simultaneously in the
      same experimental dataset. To address this gap, the present study simultaneously
      included all of these subject-specific and fracture event variables in
      multivariate models to understand their contributions to femoral strength and
      fracture type. The primary aim of this study was to determine not only whether
      each of these variables contributed to the prediction of femoral strength, but
      also to determine the relative importance of each variable in strength
      prediction. A secondary aim was to similarly characterize the importance of these
      variables for the prediction of fracture type. To accomplish these aims, we
      characterized 197 proximal femurs (covering a wide range of subject-specific
      variables) with DXA and CT scans, and then tested the femurs to fracture in a
      sideways fall on the hip configuration. Each femur was tested using one of three
      fall speed conditions and one of four angles of impact (bone orientations).
      During each test, we acquired measurements of relevant force and displacement
      data. We then reduced the test data to determine femoral strength, and we used
      post-fracture CT scans to classify the fracture type (e.g., trochanteric,
      cervical). Using these results, the explanatory variables were analyzed with
      mixed statistical models to explain variations in hip fracture strength and
      fracture type, respectively. Five explanatory variables were statistically
      significant in explaining the variability in femoral strength: aBMD, sex, age,
      fall speed, and neck-shaft angle (P <= 0.0135). These five variables, including
      significant interactions, explained 80% of the variability in hip fracture
      strength. Additionally, when only aBMD, sex, and age (P < 0.0001) were considered
      in the model, again including significant interactions, these three variables
      alone explained 79% of the variability in hip fracture strength. So while fall
      speed (P = 0.0135) and neck-shaft angle (P = 0.0041) were statistically
      significant, the inclusion of these variables did not appreciably improve the
      prediction of hip fracture strength compared to the model that considered only
      aBMD, sex and age. For the variables we included in this study, in the ranges we
      considered, our findings indicate that the clinically-available information of
      patient age, sex and aBMD are sufficient for femoral strength assessment. These
      findings also suggest that there is little value in the extra effort required to
      characterize the effect of femoral geometry on strength, or to account for the
      probabilistic nature of fall-related factors such as fall speed and angle of
      impact. For fracture type, the only explanatory variable found to be significant
      was aBMD (P <= 0.0099). We found that the odds of having intertrochanteric
      fractures increased by 47% when aBMD decreased by one standard deviation (0.2
      g/cm2).

PMID- 30096470
TI  - Breast Cancer, Secondary Breast Cancers in Childhood Cancer Male Survivors
      Characteristics and Risks.
AB  - PURPOSE: Male breast cancer (MBC) is uncommon, accounting for less than 1% of all
      breast cancers. Secondary breast cancers among childhood cancer survivors have
      been well described in the literature, but less is known about MBC. METHODS AND
      MATERIALS: We carried out an analysis in a cohort of 7019 five-year survivors of
      a solid childhood (aged <=20 years) cancer treated in France before 2001 and
      followed for an average of 20 years and compared breast cancers occurring in both
      men and women. RESULTS: Among the 7019 survivors, 4 out of 3893 male survivors
      developed breast cancer, compared with 99 out of 3126 female survivors. All of
      the men had a history of radiation therapy. The 4 men with MBC had estrogen
      receptors and 3 had progesterone receptors. CONCLUSIONS: MBC is a rare second
      malignancy among childhood cancer survivors. Receipt of radiation therapy is a
      recognized risk factor, but more data about eventual genetic mutations are
      necessary. Regular screening based only on a history of radiation therapy is not
      recommended; however, attention must be given in the case of suspicious symptoms.

PMID- 30096471
TI  - Selecting the correct scaffold model for assessing of the dielectric response of
      collagen-based biomaterials.
AB  - Fish collagen (Col) was cross-linked using two methods: dehydrothermal treatment
      (DHT) and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) in
      the presence of N-hydroxy-succinimide (NHS). For the samples marked Col, Col-DHT
      and Col-EDC/NHS, dielectric properties were measured in the frequency range from
      100 Hz to 100 kHz and temperatures from 25 to 145  degrees C. In the full
      temperature range, the average values of relative permittivity and dielectric
      losses for Col samples are lower than those recorded for Col-DHT and Col-EDC/NHS
      samples. The peak temperature of the dielectric parameters attributed to the
      denaturation temperature for Col, Col-DHT and Col-EDC/NHS, respectively, is about
      75  degrees C, 83  degrees C and 89  degrees C. In addition, the values of these
      parameters are much higher in Col-EDC/NHS than in Col-DHT at the same temperature
      and frequency. The permittivity decrement and conductivity increment,
      respectively, for Col-EDC/NHS are about 62 and 32 times greater than those given
      by Col-DHT, which is a consequence of the EDC/NHS crosslinking action. Our
      electrical and dielectric studies of fish Col cross-linked by EDC/NHS or DHT
      provide deeper insight into the structure of collagen materials and help improve
      the synthesis of Col-based scaffolds for tissue engineering.

PMID- 30096472
TI  - Role of zein incorporation on hydrophobic drug-loading capacity and colloidal
      stability of phospholipid nanoparticles.
AB  - Liposome, phosphatidylcholine nanoparticle (PC-NP), is an attractive colloidal
      carrier of hydrophobic drugs but its clinical development is often limited by low
      drug-loading capacity and the physical instability. Zein is a water-insoluble
      amphiphilic protein obtained from the corn. We herein investigated a possibility
      to develop zein-phosphatidylcholine hybrid nanoparticle (Z/PC-NP) as an advanced
      hydrophobic drug carrier. By employing the conventional liposome preparation
      method with the addition of zein, Z/PC-NP were produced. The extent of zein
      incorporation in PC-NP was affected by PC composition. DSC demonstrated the
      lowered phase transition temperature of PC by zein and FTIR showed the appearance
      of weakened but clear amide bonds of zein as well as increased levels of
      heterogeneous hydrogen bonding of Z/PC-NP compared to PC-NP. DLS, TEM and cryo
      TEM studies suggested Z/PC-NP to be spherical nanoparticles composed of a zein
      core and a zein-PC hybrid shell. Z/PC-NP exhibited a higher loading capacity for
      hydrophobic model drugs (paclitaxel, docetaxel, celecoxib and curcumin), than did
      the zein nanoparticle and PC-NP, while exhibiting an intermediate drug release
      rate. The serum stability and the storage stability of Z/PC-NP were greater than
      those of PC-NP. Zein functioned as a cryoprotectant of PC-NP during freeze
      drying. Z/PC-NP may provide a promising nanoparticle carrier of hydrophobic
      drugs.

PMID- 30096473
TI  - Real-time QCM-D monitoring of endothelial cells and macrophages adhering and
      spreading to SEMA4D/heparin surfaces.
AB  - In vitro evaluation techniques that address cellular interactions under dynamic
      circumstances are required for the development of advanced biomaterials. In this
      study, quartz crystal microbalance and dissipation (QCM-D) provided a surface
      sensitive technique that enabled real-time monitoring of the adhesion and
      spreading response of endothelial cells (ECs) and macrophages (MAs) to soluble
      semaphoring 4D (SEMA4D)/heparin modified substratum. The high heparin and low
      SEMA4D of substratum promoted ECs adhering and spreading. However, surfaces with
      high SEMA4D and low heparin enhanced MA adhering and spreading. Furthermore, DF
      plots of QCM-D indicated that the adhering and spreading of MAs were mainly
      mediated via the ligand-receptor interaction of SEMA4D-CD72, while both adhering
      and spreading of ECs were mainly mediated via heparin-induced integrin binding.
      This study suggests that QCM-D combined with other appropriate methods can be
      utilized to explore the mechanisms for cellular interaction with biomaterial
      surfaces.

PMID- 30096474
TI  - Encapsulation and modulation of protolytic equilibrium of beta-carboline-based
      norharmane drug by cucurbit[7]uril and micellar environments for enhanced
      cellular uptake.
AB  - The effect of supramolecular nanocavity on photophysical and acid-dissociation
      properties of Norharmane (NHM), a physiologically important, anxiety control and
      memory-enhancing beta-carboline-based drug, has been investigated using steady
      state absorption and fluorescence spectroscopy. Self-assembled organization
      derived from surfactants and rigid water-soluble macrocyclic host Cucurbit[7]uril
      (CB7) have been selected for this investigation. The confined-space offered by
      the supramolecular assemblies modulates the pKa value of NHM (up to 3 units) as
      it can exist in two protolytic forms at near neutral pH. Therefore, the pH
      dependent binding properties, modulation of pKa value and its consequences on the
      photophysical, chemical and solubility properties are investigated in detail.
      This investigation shows a large shift in the protolytic equilibrium which in
      turn causes ca. 15 times solubility-enhancement at near neutral pH. Moreover, the
      effect of enhanced solubility has been further investigated by the augmentation
      in the cellular uptake of NHM entrapped inside CB7. Thus, the modulation of the
      acid-base properties and solubility of beta-carboline-based drugs will have
      immense potential for their formulation, cellular uptake and bioavailability.

PMID- 30096475
TI  - The characteristics of a preservative-free contact lens care solution on lysozyme
      adsorption and interfacial friction behavior.
AB  - The population of soft contact lens wearers is increasing, thus the issues of
      feeling comfortable and contact lens-induced clinical symptoms are concerned.
      Both lysozyme deposition and mechanical friction among contact lens and the eye
      can induce discomfort and eye conditions. Therefore, we characterized our
      developed preservative-free contact lens care solution on lysozyme adsorption and
      lubrication. Two distinct lens materials were washed with the care solution after
      being soaked in lysozyme, as well as were rubbed against the glass in the
      presence of lysozyme and the care solution for measuring the friction
      coefficient. Our results demonstrated that the preservative-free contact lens
      care solution can be applied as a potential lubricant for a specific type of soft
      contact lenses.

PMID- 30096476
TI  - Synthesis, characterization and energy transfer studies of fluorescent dye
      labeled metal-chelating polymers anchoring pendant thiol groups for surface
      modification of quantum dots and investigation on their application for pH
      responsive controlled release of doxorubicin.
AB  - We describe the synthesis of an end-functionalized fluorescent dye-labeled poly(N
      (2-thiolethyl methacrylamide) as a metal chelating polymer with a very narrow
      size distribution and controllable molecular weights by reversible addition
      fragmentation chain transfer polymerization. In following, we apply this water
      soluble metal-chelating polymer for surface modification of cadmium telluride
      quantum dots (CdTe QDs) by ligand exchange method. The obtained poly(N-(2
      thiolethyl methacrylamide)/CdTe QDs hybrid was fully characterized using Fourier
      transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TG) and
      transmission electron microscopy (TEM). The size of the prepared hybrid was
      estimated around 3.2 nm by TEM. Furthermore, we used this hybrid for improving
      the release performance of doxorubicin hydrochloride as a chemotherapeutic model
      drug. The in vitro release of doxorubicin was studied in pH 5.4 and 7.4, which
      release curves were nicely fitted by the Korsemeyer-Peppas equation and the
      release followed by non-Fickian diffusion or anomalous diffusion in pH 5.4. The
      synthesized fluorescent dye-labeled hybrid can be used as a donor-acceptor pair
      for fluorescence resonance energy transfer (FRET) experiments, so the energy
      transfer behavior between fluorescent dye as a donor and CdTe QDs as an acceptor
      were interrogated using Forster/fluorescence resonance energy transfer model,
      which the distance was found to be 3.95 nm. This present work has potential for
      both diagnostic and therapeutic aspects for cancer patients.

PMID- 30096477
TI  - Formulation and in vitro evaluation of magnetoliposomes as a potential nanotool
      in colorectal cancer therapy.
AB  - Magnetoliposomes (MLPs) offer many new possibilities in cancer therapy and
      diagnosis, including the transport of antitumor drugs, hyperthermia treatment,
      detection using imaging techniques, and even cell migration. However, high
      biocompatibility and functionality after cell internalization are essential to
      their successful application. We synthesized maghemite nanoparticles (gamma
      Fe2O3) by oxidizing magnetite cores (Fe3O4) and coating them with
      phosphatidylcholine (PC) liposomes, obtained using the thin film hydration
      method, to generate MLPs. The MLPs were tested in vitro, using human tumor and
      non-tumor colon cell lines, for cytotoxicity, cell uptake and cellular
      distribution, and magnetically-induced cell mobility. In addition, blood cells
      biocompatibility studies were performed. The mean size of the MLPs, with a core
      of gamma-Fe2O3 completely surrounded by PC liposomes, was 90 +/- 20 nm, showing a
      soft magnetic character and a great biocompatibility in all the cell lines
      assayed including blood cells. Prussian blue staining showed a high MLP cell
      uptake with maximum internalization at 24 h. TEM analysis showed the MLPs
      surrounded by the cell membrane and in the cell periphery, suggesting
      internalization by endocytosis and/or macropinocytosis. Interestingly, the
      mitochondria presented MLP accumulations, particularly in tumor cells. Finally,
      MLPs within colon cancer cells were able to induce cell migration when a magnetic
      field was applied in vitro, indicating the functionality of our nanoformulation.
      A promising biomedical application of these MLPs is anticipated based on their
      physical, chemical and biological properties.

PMID- 30096478
TI  - Effects of copper on hemocyte parameters in the estuarine oyster Crassostrea
      rivularis under low pH conditions.
AB  - With the development of industry and agriculture, the metal pollutants (e.g., Cu)
      are inevitably released into the aquatic environment. In addition, ocean
      acidification (OA) as a major environmental stress is affecting marine organisms.
      In this study, we investigated the hemocyte responses of the estuarine oyster
      Crassostrea rivularis exposed to six combinations of two pH levels (8.1 and 7.7)
      and three Cu concentrations (0, 10 and 50 MUg/l) using flow cytometry in vitro
      and in vivo. In both experiments, Cu and low pH jointly affected the hemocyte
      parameters of oyster. High Cu exposure resulted in decreased total hemocyte count
      (THC), esterase activity (EA) and lysosomal content (LC) and increased hemocyte
      mortality (HM), phagocytosis activity (PA) and reactive oxygen species (ROS)
      production, especially under low pH conditions. The immune suppression of metal
      exposure was more significant than low pH exposure with a 28-d experimental
      period in oysters. A slight recovery of the immune parameters was observed in
      THC, HM, PA, ROS and LC. During the depuration period, the modulatory effects of
      pH were still obvious. In addition, carry-over effects of high Cu and low pH were
      still observed. Overall, our results showed that copper and low pH weaken immune
      functions of hemocyte in oysters, with synergistic effects. This work provides
      new evidence of sublethal negative effects of metals on marine animals under
      global change scenarios, and copper likely leads to reduced fitness of oysters
      under low pH conditions.

PMID- 30096479
TI  - CREB element is essential for unfolded protein response (UPR) mediating the Cu
      induced changes of hepatic lipogenic metabolism in Chinese yellow catfish
      (Pelteobagrus fulvidraco).
AB  - The present study was conducted to explore the underlying mechanism of unfolded
      protein response (UPR) mediating the Cu-induced changes of hepatic lipogenic
      metabolism in a low vertebrate, freshwater teleost yellow catfish Pelteobagrus
      fulvidraco. To this end, three experiments were conducted. In Exp. 1, we cloned
      the regions of grp78, perk, ire-1alpha and atf-6alpha promoters, and found that
      multiple cAMP-response element binding protein (CREB) binding sites were
      identified in their promoter regions. Furthermore, these CREB binding sites
      played crucial role in transcriptional regulation of UPR. In Exp. 2, the
      involvement of perk, ire-1alpha and atf-6alpha in Cu-induced changes of hepatic
      lipid metabolism was confirmed by specific miRNA. In Exp. 3, the regulatory
      mechanism of CREB underlying UPR mediating Cu-induced hepatic lipogenic
      metabolism were investigated. Cu induced UPR via the activation of CREB binding
      sites in the promoter regions of grp78, perk, ire-1alpha and atf-6alpha. In
      addition, the inhibition of CREB markedly attenuated the Cu-induced up-regulation
      of hepatic lipogenic metabolism in hepatocytes. This conclusion was further
      supported by the results from the trial of CREB over-expression. Taken together,
      the present study indicated that CREB was essential for UPR mediating Cu-induced
      lipogenic metabolism, supporting a mechanistic link among CREB, UPR and Cu
      induced changes of lipid metabolism.

PMID- 30096481
TI  - Activity of Afatinib in Heavily Pretreated Patients With ERBB2 Mutation-Positive
      Advanced NSCLC: Findings From a Global Named Patient Use Program.
AB  - INTRODUCTION: Approximately 1% to 4% of NSCLC tumors harbor erb-b2 receptor
      tyrosine kinase 2 (ERBB2) mutation; there is no approved targeted treatment for
      this subgroup. METHODS: Patients with stage IV NSCLC that progressed after
      clinical benefit on erlotinib/gefitinib and/or had activating EGFR or ERBB2
      mutations, had exhausted other treatments, and were ineligible for afatinib
      trials were enrolled in a named patient use program, receiving afatinib 30 to 50
      mg/d on a compassionate basis within routine clinical practice. Efficacy and
      safety were retrospectively assessed in the subgroup with ERBB2 mutation-positive
      NSCLC. RESULTS: Twenty-eight heavily pretreated patients in the named patient use
      program had a documented ERBB2 mutation by local testing. Median time-to
      treatment failure (TTF; time from treatment initiation to discontinuation for any
      reason) was 2.9 months; eight patients (29%) had TTF greater than 1 year.
      Objective response rate was 19% (3 of 16 patients with response data achieved
      partial response) and disease control rate (DCR) was 69% (11 of 16). Among 12
      patients for whom type of ERBB2 mutation was specified, 10 had a
      p.A775_G776insYVMA insertion in exon 20, four of whom (40%) remained on afatinib
      for more than 1 year. This subgroup had median TTF of 9.6 months, objective
      response rate of 33% (two of six), and disease control rate of 100% (six of six).
      CONCLUSIONS: This analysis of patients treated in clinical practice provides
      further evidence of the activity of afatinib in ERBB2 mutation-positive NSCLC,
      and suggests that identification of specific subgroups with certain mutations,
      such as p.A775_G776ins/YVMA insertion in exon 20, could help optimize outcomes
      with ErbB2-targeted treatment.

PMID- 30096482
TI  - Identifying others' informative intentions from movement kinematics.
AB  - Previous research has demonstrated that people can reliably distinguish between
      actions with different instrumental intentions on the basis of the kinematic
      signatures of these actions (Cavallo, Koul, Ansuini, Capozzi, & Becchio, 2016).
      It has also been demonstrated that different informative intentions result in
      distinct action kinematics (McEllin, Knoblich, & Sebanz, 2017). However, it is
      unknown whether people can discriminate between instrumental actions and actions
      performed with an informative intention, and between actions performed with
      different informative intentions, on the basis of kinematic cues produced in
      these actions. We addressed these questions using a visual discrimination
      paradigm in which participants were presented with point light animations of an
      actor playing a virtual xylophone. We systematically manipulated and amplified
      kinematic parameters that have been shown to reflect different informative
      intentions. We found that participants reliably used both spatial and temporal
      cues in order to discriminate between instrumental actions and actions performed
      with an informative intention, and between actions performed with different
      informative intentions. Our findings indicate that the informative cues produced
      in joint action and teaching go beyond serving a general informative purpose and
      can be used to infer specific informative intentions.

PMID- 30096480
TI  - Developmental neurotoxicity of triphenyl phosphate in zebrafish larvae.
AB  - Triphenyl phosphate (TPhP), a typical organophosphate ester, is frequently
      detected in the environment and biota samples. It has been implicated as a
      neurotoxin as its structure is similar to neurotoxic organophosphate pesticides.
      The purpose of the present study was to investigate its potential developmental
      neurotoxicity in fish by using zebrafish larvae as a model. Zebrafish (Danio
      rerio) embryos were exposed to 0.8, 4, 20 and 100 MUg/L of TPhP from 2 until 144
      h post-fertilization. TPhP was found to have high bioconcentrations in zebrafish
      larvae after exposure. Further, it significantly reduced locomotor activity as
      well as the heart rate at the 100 MUg/L concentration. TPhP exposure
      significantly altered the content of the neurotransmitters gamma-aminobutyric and
      histamine. Downregulation of the genes related to central nervous system
      development (e.g., alpha1-tubulin, mbp, syn2a, shha, and elavl3) as well as the
      corresponding proteins (e.g., alpha1-tubulin, mbp, and syn2a) was observed, but
      the gap-43 protein was found to upregulated. Finally, marked inhibition of total
      acetylcholinesterase activity, which is considered as a biomarker of
      neurotoxicant exposure, was also observed in the larvae. Our results indicate
      that exposure to environmentally relevant concentrations of TPhP can affect
      different parameters related to center nervous system development, and thus
      contribute to developmental neurotoxicity in early developing zebrafish larvae.

PMID- 30096483
TI  - Subconscious processing reveals dissociable contextual modulations of visual size
      perception.
AB  - Visual size perception is highly context-dependent. In a series of experiments
      reported here, we demonstrated that the contextual modulation of visual size
      processing could occur independent of conscious awareness. Specifically, the
      Ebbinghaus illusion, which is mediated by lateral connections within the early
      visual processing stream, persisted even when the surrounding inducers were
      rendered invisible. Moreover, when the central target was initially interocularly
      suppressed, the identical target emerged from suppression faster when surrounded
      by small relative to large inducers, with the suppression time difference well
      predicted by the strength of the illusion. By contrast, there were no such
      subconscious contextual modulation effects associated with the Ponzo illusion,
      which largely relies on feedback projections to the early visual cortices. These
      results indicate that contextual information can modulate visual size perception
      without conscious awareness, and the dissociated modulation effects further
      suggest that subconscious contextual modulation takes place in the early visual
      processing stream and is largely independent of high-level feedback influences.

PMID- 30096484
TI  - Lithium affects rat hippocampal electrophysiology and epileptic seizures in a
      dose dependent manner.
AB  - Lithium, a classic mood stabilizer, prevents apoptosis-dependent cellular death
      and has garnered considerable interest as a neuroprotective agent that is
      efficacious in the treatment of many neurological diseases. However, the effects
      of lithium in epilepsy remain controversial. We found that different doses of
      lithium affect epileptic seizure activity and bidirectionally modulate the
      susceptibility to and severity of seizures induced by pilocarpine in rats.
      Recently, it has been demonstrated that systematically administered lithium
      affects the powers of hippocampal gamma and theta oscillations in baseline
      electroencephalograms. Low-dose lithium (10 mg/kg) administered to pilocarpine
      treated rats markedly increased the powers of basal gamma (30-80 Hz) and theta (4
      12 Hz) oscillations, decreased the proportion of Racine stage 4-5 seizures,
      extended latency until seizure onset, and significantly reduced the frequency of
      lower-class seizures (p < 0.05). Conversely, when the dose was increased to 40
      mg/kg, lithium reduced the frequency of lower-class seizures compared to control
      treatment (p < 0.05). Further, at this high dose, lithium reduced the power of
      basal gamma oscillations and markedly increased the susceptibility to and
      severity of pilocarpine-induced seizures and enhanced ripple rhythms (80-200 Hz)
      postictally. Our results provide a framework for further investigations of the
      underlying electrophysiological mechanisms of lithium-induced imbalances in
      excitatory and inhibitory neural circuits that regulate seizure activity in rats.
      In conclusion, the observed in vivo changes in the powers of basal gamma and
      theta oscillations in response to different doses of lithium may reflect
      hippocampal neural network responsiveness.

PMID- 30096485
TI  - The criminal association of Leishmania parasites and viruses.
AB  - In nature, humans infected with protozoan parasites can encounter viruses, which
      could alter their host immune response. The impact of viruses on human parasitic
      diseases remains largely unexplored due to the highly sterilized environment in
      experimental studies and the difficulty to draw a correlation between co
      infection and pathology. Recent studies show that viral infections exacerbate
      pathology and promote dissemination of some Leishmania infections, based on a
      hyper-inflammatory reaction driven by type I interferons. Thus, not only the
      infecting parasite species, but also bystander viral infections could be a major
      determinant of the outcome of Leishmania infection. In this review, we focus on
      the contribution of viral co-infection to the exacerbation of leishmaniasis's
      pathology and its possible impact on treatment and vaccination strategies.

PMID- 30096487
TI  - The effect of repeated-intermittent exposure to 5-methoxy-N,N
      diisopropyltryptamine (5-MeO-DIPT) during adolescence on learning and memory in
      adult rats.
AB  - BACKGROUND: According to the European Drug Report, the use of novel psychoactive
      substances (NPS) is constantly growing. NPS are widely abused by human adolescent
      subjects. 5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) is one of the most
      frequently used hallucinogenic NPS. 5-MeO-DIPT intoxication results in
      hallucinations, vomiting, and tachycardia. Long-term exposure to 5-MeO-DIPT was
      reported to lead to development of post-hallucinogenic perception disorder. The
      aim of the present study was to determine whether repeated-intermittent
      administration of 5-MeO-DIPT during adolescence affects learning and memory in
      adult rats. METHODS: Rats were treated with 5-MeO-DIPT in a dose of 2.5mg/kg from
      30 to 33 and 37 to 40 Postnatal Day (PND). The experiments were conducted when
      the animals reached 90 PND. The effect of 5-MeO-DIPT on cognitive functions was
      assessed using the novel object recognition, open field, and serial pattern
      learning (SPL) tests. RESULTS: Repeated-intermittent exposure to 5-MeO-DIPT
      during adolescence decreased the number of crossings in the open field test at
      adulthood. Moreover, 5-MeO-DIPT treatment impaired adult rats' learning in the
      SPL test. There was no change in the novel object recognition test. CONCLUSIONS:
      The present results show that the performance of adult rats treated with 5-MeO
      DIPT during adolescence was impaired in the open field test, which indicates the
      attenuated exploratory activity. 5-MeO-DIPT treatment undermined adult rats'
      performance in the serial pattern learning test, suggesting impairment of long
      term memory and cognitive flexibility. The present study showed that the exposure
      to 5-MeO-DIPT during adolescence might lead to long-lasting behavioral changes
      which persisted long after the exposure period.

PMID- 30096486
TI  - Ischemic tau protein gene induction as an additional key factor driving
      development of Alzheimer's phenotype changes in CA1 area of hippocampus in an
      ischemic model of Alzheimer's disease.
AB  - BACKGROUND: Tauopathies are a class of neurodegenerative illnesses associated
      with the aberrant accumulation of the tau protein in the brain. The best known
      out of these diseases is Alzheimer's disease, a disorder where the microtubule
      associated tau protein becomes hyperphosphorylated (which lowers its binding
      affinity to microtubules) and accumulates inside neurons in the form of tangles.
      In this study, we attempt to find out whether brain ischemia may play an
      important role in tau protein gene alterations. METHODS: We have investigated the
      relationship between hippocampal ischemia and Alzheimer's disease by means of a
      transient 10-min global brain ischemia in rats and determining the effect on
      Alzheimer's disease tau protein gene expression during 2, 7 and 30 days post
      injury. RESULTS: We found the significant overexpression of tau protein gene on
      the 2nd day, but on day's 7 and 30 post-ischemia there a significant opposite
      tendency was observed. CONCLUSION: The obtained results offer a novel insight
      into tau protein gene in regulating delayed neuronal death in the ischemic
      hippocampus. Finally, these findings further elucidate the long-term impact of
      brain ischemia on Alzheimer's disease development.

PMID- 30096488
TI  - In vitro and in silico approaches to unveil the mechanisms underlying the
      cytotoxic effect of juncunol on human hepatocarcinoma cells.
AB  - BACKGROUND: Juncunol is a phenanthrene isolated from the halophyte species Juncus
      acutus, with selective cytotoxic activity towards human hepatocarcinoma (HepG2)
      cells. However, its mechanism of action is unknown. METHODS: The in vitro
      cytotoxic mechanism of juncunol was evaluated on HepG2 cells through several
      methods to elucidate its potential to induce apoptotic features, decrease
      mitochondrial membrane potential, promote internal ROS production and influence
      cell cycle. We also report its haemolytic activity on human erythrocytes and in
      silico DNA-binding studies. RESULTS: Juncunol induced an increase in the number
      of apoptotic cells in a concentration-dependent manner, accompanied by a decrease
      in the mitochondrial membrane potential. No significant differences were observed
      in production of reactive oxygen species (ROS). Moreover, juncunol application at
      the IC50 value significantly induced cell cycle arrest in the G0/G1 phase
      comparatively to the control group. No significant haemolysis was detected. In
      silico studies indicate that juncunol seems to bind between GC base pairs.
      CONCLUSION: Juncunol reduced HepG2 cells proliferation through the induction of
      apoptotic cellular death, in a concentration-dependent manner. Apoptosis
      induction seems to be related with a decrease of the mitochondrial membrane
      potential but not with ROS production. Juncunol had no haemolytic activity and
      may act as a DNA intercalator. Our data suggests juncunol as a suitable candidate
      for more detailed studies, including in vivo experiments, in order to completely
      characterize its mode of action.

PMID- 30096489
TI  - Bisphosphonates: Future perspective for neurological disorders.
AB  - Neurodegenerative disorders and osteoporosis share some common underlying
      pathological features including calcium overload, accumulation of toxic
      chemicals, inflammation and impaired protein prenylation by isoprenoids (farnesyl
      pyrophosphate and geranylgeranyl pyrophosphate) appear later stage of life.
      Substantial number of pre-clinical and clinical reports as well as in vitro data
      univocally acknowledged the negative impact of altered post-translational
      modification (prenylation) of proteins like small GTPases (Rffhes, Rho, Rac etc.)
      and cholesterol levels in both serum and brain on CNS integrity. Bisphosphonates
      (BPs), referred to as gold standard for osteoporosis treatment, have well
      established role in attenuation of bone resorption and osteoclast apoptosis by
      inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate
      pathway. BPs mainly nitrogen containing BPs (NBPs) have potential to offer new
      therapeutic targets for neurological disorders and received increasing attention
      in recent years. A year back clinical and pre-clinical studies revealed that NBPs
      have the potential to alleviate the symptoms of neurological disorders like brain
      calcification, Alzheimer's disease and Huntington's disease by targeting
      mevalonate pathway. Though these drugs have well developed role in inhibition of
      isoprenoids synthesis, these were demonstrated to inhibit acetyl cholinesterase
      enzyme and cholesterol synthesis in brain that are considered as the critical
      factors for impairment of cognitive functions which is the hallmark of several
      neurological disorders. Still the current understanding of BPs' effect in CNS is
      limited due to lack of studies focusing the molecular and cellular mechanism. The
      present review aims to reveal the updated discussion on the mechanism
      contributing BPs' effect in CNS disorders.

PMID- 30096490
TI  - The effect of reward on listening effort as reflected by the pupil dilation
      response.
AB  - Listening to speech in noise can be effortful but when motivated people seem to
      be more persevering. Previous research showed effects of monetary reward on
      autonomic responses like cardiovascular reactivity and pupil dilation while
      participants processed auditory information. The current study examined the
      effects of monetary reward on the processing of speech in noise and related
      listening effort as reflected by the pupil dilation response. Twenty-four
      participants (median age 21 yrs) performed two speech reception threshold (SRT)
      tasks, one tracking 50% correct (hard) and one tracking 85% correct (easy), both
      of which they listened to and repeated sentences uttered by a female talker. The
      sentences were presented with a single male talker or, in a control condition, in
      quiet. Participants were told that they could earn a high (5 euros) or low (0.20
      euro) reward when repeating 70% or more of the sentences correctly. Conditions
      were presented in a blocked fashion and during each trial, pupil diameter was
      recorded. At the end of each block, participants rated the effort they had
      experienced, their performance, and their tendency to quit listening.
      Additionally, participants performed a working memory capacity task and filled in
      a need-for-recovery questionnaire as these tap into factors that influence the
      pupil dilation response. The results showed no effect of reward on speech
      perception performance as reflected by the SRT. The peak pupil dilation showed a
      significantly larger response for high than for low reward, for the easy and hard
      conditions, but not the control condition. Higher need for recovery was
      associated with a higher subjective tendency to quit listening. Consistent with
      the Framework for Understanding Effortful Listening, we conclude that listening
      effort as reflected by the peak pupil dilation is sensitive to the amount of
      monetary reward.

PMID- 30096491
TI  - Human frequency following responses to iterated rippled noise with positive and
      negative gain: Differential sensitivity to waveform envelope and temporal fine
      structure.
AB  - The perceived pitch of iterated rippled noise (IRN) with negative gain (IRNn) is
      an octave lower than that of IRN with positive gain (IRNp). IRNp and IRNn have
      identical waveform envelopes (ENV), but differing stimulus waveform fine
      structure (TFS), which likely accounts for this perceived pitch difference. Here,
      we examine whether differences in the temporal pattern of phase-locked activity
      reflected in the human brainstem Frequency Following Response (FFR) elicited by
      IRNp and IRNn can account for the differences in perceived pitch for the two
      stimuli. FFRs using a single onset polarity were measured in 13 normal-hearing,
      adult listeners in response to IRNp and IRNn stimuli with 2 ms, and 4 ms delay.
      Autocorrelation functions (ACFs) and Fast Fourier Transforms (FFTs) were used to
      evaluate the dominant periodicity and spectral pattern (harmonic spacing) in the
      phase-locked FFR neural activity. For both delays, the harmonic spacing in the
      spectra corresponded more strongly with the perceived lowering of pitch from IRNp
      to IRNn, compared to the ACFs. These results suggest that the FFR elicited by a
      single polarity stimulus reflects phase-locking to both stimulus ENV and TFS. A
      post-hoc experiment evaluating the FFR phase-locked activity to ENV (FFRENV), and
      TFS (FFRTFS) elicited by IRNp and IRNn confirmed that only the phase-locked
      activity to the TFS, reflected in FFRTFS, showed differences in both spectra and
      ACF that closely matched the pitch difference between the two stimuli. The
      results of the post-hoc experiment suggests that pitch-relevant information is
      preserved in the temporal pattern of phase-locked activity and suggests that the
      differences in stimulus ENV and TFS driving the pitch percept of IRNp and IRNn
      are preserved in the brainstem neural response. The scalp recorded FFR may
      provide for a noninvasive analytic tool to evaluate the relative contributions of
      envelope and temporal fine-structure in the neural representation of complex
      sounds in humans.

PMID- 30096492
TI  - Intraoperative Stereotactic Magnetic Resonance Imaging for Deep Brain Stimulation
      Electrode Planning in Patients with Movement Disorders.
AB  - OBJECTIVE: Implantation of deep brain stimulation (DBS) electrodes requires
      stereotactic imaging. Stereotactic magnetic resonance imaging (MRI) for DBS
      surgery has become more popular and intraoperative MRI scanners have become more
      available. We report on our cohort of movement disorder patients who underwent
      intraoperative stereotactic MRI-only DBS electrode implantation. METHODS: A
      review of our DBS database for eligible patients over a study period of 8 years
      was performed. Stereotactic accuracy was calculated as a directional error and
      the Euclidean distance between planned and controlled electrode positions. Number
      and choice of microelectrodes, procedural times and complications were
      documented. RESULTS: n = 86 surgeries in n = 81 patients with Parkinson's Disease
      (PD), essential tremor and dystonia were performed and n=167 electrodes were
      implanted. Mean Euclidean distance between planned and controlled target was
      2.1mm (+/-0.6). The directional error showed that electrodes were implanted more
      medial (0.3mm +/- 0.9), posterior (0.5mm +/- 1.0) and inferior (0.6mm +/-1.0)
      compared to plan. There were no significant differences for stereotactic accuracy
      between targets, hemispheres or order of implantation. No significant
      correlations between Euclidean distance and number of microelectrode tracts or
      volume of intracranial air were observed. N = 539 microelectrodes were applied.
      In 28.7% non-center trajectories were chosen. Length of tremor (-61 minutes) and
      PD (-121 minutes) surgeries could be reduced significantly over the course of the
      study period. N = 1 (1.2%) intracranial hemorrhage occurred. N = 1 (0.6%)
      electrode had to be repositioned for lack of clinical effect. CONCLUSION:
      Intraoperative stereotactic MRI for DBS surgery is feasible with high
      stereotactic accuracy and low rates of complication.

PMID- 30096493
TI  - The End-to-Side Anastomosis: A Comparative Analysis of Arterial Models in the
      Rat.
AB  - BACKGROUND: The end-to-side anastomosis is 1 of the most common anastomosis
      configurations used in cerebrovascular surgery. Although several living practice
      models have been proposed for this technique, few involve purely arterial
      vessels. The purpose of the present study was to compare 2 arterial models using
      common carotid arteries (CCAs) and common iliac arteries (CIAs) in rats. METHODS:
      The CIAs and CCAs were exposed in 10 anesthetized rats, and their lengths and
      diameters were measured. Also, the mobilization extent of each vessel along its
      contralateral counterpart was measured after each artery had been transected at
      its proximal exposure point. We also studied the technical advantages and
      disadvantages of each model for practicing end-to-side anastomosis. RESULTS: The
      average diameters of the CCA and CIA were 1.1 and 1.3 mm, respectively. The
      average extent of mobilization along the contralateral vessel was 13.9 mm and
      10.3 mm for CCA and CIA, respectively. The CCA model had the advantages of
      greater arterial redundancy (allowing completion of both suture lines
      extraluminally) and a minimal risk of venous injury. The main disadvantage of the
      CCA model was the risk of cerebral ischemia. The CIA model was not limited by the
      ischemic time and provided the technical challenge of microsurgical dissection of
      the common iliac vein from the CIA, although it had limited CIA redundancy.
      CONCLUSIONS: Both CCA and CIA models could be efficiently used for practicing the
      end-to-side anastomosis technique. Each model provides the trainee with a
      specific set of advantages and disadvantages that could help with the optimal
      selection of the practice model according to trainee's skill level.

PMID- 30096495
TI  - Transcondylar Fossa Approach to Unruptured Vertebral Artery and Vertebral Artery
      Posterior Inferior Cerebellar Artery Aneurysms: Surgical Outcome.
AB  - OBJECTIVE: Surgical treatment of vertebral artery (VA) and VA-proximal posterior
      inferior cerebellar artery (PICA) aneurysms poses a special challenge to the
      operating surgeon because of the complex anatomy of the neck and the location of
      the aneurysm. We report our surgical results of unruptured VA and VA-PICA
      aneurysms operated on through the transcondylar fossa approach. METHODS: We
      retrospectively analyzed the data of 20 patients with unruptured VA and VA-PICA
      aneurysms who were treated by the transcondylar fossa approach in a single
      institution from November 2014 to March 2018. Data including clinical profile,
      radiology, complications, and outcome were analyzed. RESULTS: Five patients had
      VA aneurysms and 15 had VA-PICA aneurysms. All were unruptured aneurysms, and 4
      patients were symptomatic. All underwent surgical treatment through the
      transcondylar fossa approach. Proximal VA occlusion alone for 4 patients along
      with revascularization for 3 patients was performed. Twelve patients underwent
      clipping and 1 underwent wrapping of the aneurysm. The transcondylar fossa
      approach was adequate to expose the aneurysms successfully. There were no
      intraoperative complications encountered. Only 3 patients had transient
      postoperative complications. Follow-up imaging showed complete occlusion of all
      clipped aneurysms and complete thrombosis of the sac in all patients with
      proximal VA occlusion with or without revascularization. CONCLUSIONS: Although
      the incidence of rupture of asymptomatic unruptured VA and VA-PICA aneurysms is
      low, they should be considered for surgical treatment because they carry higher
      early mortality and morbidity after rupture. The transcondylar fossa approach
      provides adequate exposure of the aneurysm without permanent lower cranial nerve
      morbidity.

PMID- 30096494
TI  - Toxicity of Radiosurgery for Brainstem Metastases.
AB  - BACKGROUND: Although stereotactic radiosurgery (SRS) is an effective modality in
      the treatment of brainstem metastases (BSM), radiation-induced toxicity remains a
      critical concern. To better understand how severe or life-threatening toxicity is
      affected by the location of lesions treated in the brainstem, a review of all
      available studies reporting SRS treatment for BSM was performed. METHODS: Twenty
      nine retrospective studies investigating SRS for BSM were reviewed. RESULTS: The
      rates of grade 3 or greater toxicity, based on the Common Terminology Criteria
      for Adverse Events, varied from 0 to 9.5% (mean 3.4 +/- 2.9%). Overall, the
      median time to toxicity after SRS was 3 months, with 90% of toxicities occurring
      before 9 months. A total of 1243 cases had toxicity and location data available.
      Toxicity rates for lesions located in the medulla were 0.8% (1/131), compared
      with midbrain and pons, respectively, 2.8% (8/288) and 3.0% (24/811).
      CONCLUSIONS: Current data suggest that brainstem substructure location does not
      predict for toxicity and lesion volume within this cohort with median tumor
      volumes 0.04-2.8 cc does not predict for toxicity.

PMID- 30096496
TI  - Intracranial Hemorrhage After Superficial Temporal Artery-Middle Cerebral Artery
      Direct Anastomosis for Adults with Moyamoya Disease.
AB  - BACKGROUND: Intracranial hemorrhage, such as intracerebral hemorrhage (ICH),
      subarachnoid hemorrhage (SAH), and intraventricular hemorrhage (IVH), is an
      extremely rare complication after surgical revascularization for moyamoya disease
      (MMD). However, the incidence, timing, prognosis, possible mechanism, and
      prevention are not well known. METHODS: Adult patients with MMD who underwent
      direct bypass or combined bypass and experienced ICH, SAH, or IVH within 7 days
      postoperatively were enrolled in this study. The medical records and radiologic
      findings of these patients, together with their intraoperative video recordings,
      were reviewed retrospectively. RESULTS: Direct superficial temporal artery (STA)
      middle cerebral artery (MCA) bypass or combined bypass was performed for 222
      hemispheres in 193 adult patients with MMD between January 2001 and December
      2016. Intracranial hemorrhage occurred perioperatively in 8 hemispheres (3.6%) in
      8 patients. The hemorrhages developed immediately after STA-MCA direct
      anastomosis during surgery in 3 patients. Hemorrhage on computed tomography and
      neurologic deterioration were also observed immediately postoperatively in 2
      patients and during the postoperative period in 3 patients. Although 4 patients
      received medical management, neurosurgical treatment was needed in the other 4
      patients. One patient died, and 6 patients were left with moderate or severe
      disabilities. CONCLUSIONS: Intracranial hemorrhage (ICH, IVH, or SAH) after
      direct bypass for adult patients with MMD is an extremely rare but fatal
      complication. Although these hemorrhages can be associated with hyperperfusion
      syndrome, no effective prevention has been established.

PMID- 30096497
TI  - Analysis of Multimodal Intraoperative Monitoring During Intramedullary Spinal
      Ependymoma Surgery.
AB  - OBJECTIVE: To evaluate the validity of intraoperative somatosensory-evoked
      potential (SSEP) and motor-evoked potential (MEP) monitoring according to 2
      different warning criteria during 6 months from intramedullary spinal ependymoma
      surgery. METHODS: Twenty-six patients who underwent intramedullary spinal
      ependymoma surgery with intraoperative monitoring from January 2010 to June 2017
      were retrospectively analyzed. We examined the sensitivity, specificity, positive
      predictable value, negative predictable value, and diagnostic odds ratio of SSEP
      and MEP monitoring for each extremity according to 2 warning criteria: 50%
      decline and all-or-none. The postoperative motor deficit was evaluated using the
      Medical Research Council scale. The postoperative neurologic deficit was followed
      up during 6 months. RESULTS: Eighty-six extremities were evaluated. The success
      rates of SSEP and MEP monitoring were 84.9% and 83.7%, respectively.
      Indeterminate cases were 1 in SSEP and 6 in MEP. All-or-none criterion in SSEP
      and MEP monitoring showed greater specificity, positive predictable value, and
      diagnostic odds ratio than 50% decline criterion during 6 months. The validity of
      SSEP was high in the upper extremity, whereas that of MEP was high in the lower
      extremity. During the follow-up, 37 of 38 extremities (97.4%) and 18 of 29
      extremities (62.1%) showed improvement in sensory and motor deficit,
      respectively. Seven indeterminate cases also showed good clinical outcomes.
      CONCLUSIONS: Many false-positive and false-negative results of SSEP and MEP
      monitoring occurred during the immediate postoperative period. All-or-none
      criterion was more beneficial for assessing postoperative neurologic status than
      50% decline criterion. This trend was maintained until 6 months after surgery.

PMID- 30096498
TI  - Development of Machine Learning Algorithms for Prediction of 5-Year Spinal
      Chordoma Survival.
AB  - BACKGROUND: Chordomas are locally invasive slow-growing tumors that are difficult
      to study because of the rarity of the tumors and the lack of significant volumes
      of patients with longitudinal follow-up. As such, there are currently no machine
      learning studies in the chordoma literature. The purpose of this study was to
      develop machine learning models for survival prediction and deploy them as open
      access web applications as a proof of concept for machine learning in rare
      nervous system lesions. METHODS: The National Cancer Institute's Surveillance,
      Epidemiology, and End Results program database was used to identify adult
      patients diagnosed with spinal chordoma between 1995 and 2010. Four machine
      learning models were used to predict 5-year survival for spinal chordoma and
      assessed by discrimination, calibration, and overall performance. RESULTS: The 5
      year overall survival for 265 patients with spinal chordoma was 67.5%. Variables
      used for prediction were age at diagnosis, tumor size, tumor location, extent of
      tumor invasion, and extent of surgery. For 5-year survival prediction, the Bayes
      Point Machine achieved the best performance with a c statistic of 0.80,
      calibration slope of 1.01, calibration intercept of 0.03, and Brier score of
      0.16. This model for 5-year mortality prediction was incorporated into an open
      access application and can be found online (https://sorg
      apps.shinyapps.io/chordoma/). CONCLUSIONS: This analysis of patients with spinal
      chordoma demonstrated that machine learning models can be developed for survival
      prediction in rare pathologies and have the potential to serve as the basis for
      creation of decision support tools in the future.

PMID- 30096499
TI  - Case of Lumbar Schwannoma Presenting with Isolated Signs and Symptoms of
      Intracranial Hypertension.
AB  - BACKGROUND: Hydrocephalus and intracranial hypertension are rare signs of spinal
      tumors when presenting in isolation, particularly with benign tumors. CASE
      DESCRIPTION: Herein reported is a case of a 53-year-old woman who presented with
      headache, blurry vision, communicating hydrocephalus, and intracranial
      hypertension. No primary intracranial pathology was identified, and there were no
      clinical signs or symptoms of intraspinal pathology. Lumbar puncture revealed
      elevated opening pressure, cerebrospinal fluid protein, and suspected tumor cells
      in the cerebrospinal fluid, thus prompting spinal imaging. A primary lumbar
      schwannoma was subsequently determined to underlie her symptoms, which resolved
      with tumor resection. CONCLUSIONS: Clinical suspicion of spinal pathology should
      be maintained in patients with unexplained intracranial hypertension, even in the
      absence of localizing signs of spinal pathology.

PMID- 30096500
TI  - Patterns of Hydrocephalus in Rural Haiti: A Computed Tomography-Based Study.
AB  - INTRODUCTION/OBJECTIVE: Hydrocephalus is a common neurosurgical disorder that can
      lead to significant disability or death if not promptly identified and treated.
      Data on the burden of hydrocephalus in low-income countries are limited, given a
      lack of radiologic resources for the diagnosis of this condition. Here, we
      present an analysis of patterns of hydrocephalus from a large sample of computed
      tomography (CT) scans of the head performed at a public hospital in rural Haiti,
      a low-income country in the Caribbean. METHODS: We analyzed reports from 3614 CT
      scans of the head performed between July 2013 and January 2016 for findings that
      were consistent with a diagnosis of hydrocephalus (report indicating
      "hydrocephalus," "ventriculomegaly," or "enlargement of the ventricles").
      Extracted data included demographics, study indication, radiologic findings, and
      reported etiology of hydrocephalus. RESULTS: In total, 119 scans had findings
      concerning for hydrocephalus (3.5% of all scans, 6.3% of abnormal scans; age
      range 0-90 years; median age 35.5 years; 49.6% male). Pediatric patients (<18
      years of age) accounted for 39% of cases. In total, 113 of 119 (95%) scans had
      indications for possible neurosurgical intervention. Among these 113 scans, 36
      (30%) scans demonstrated communicating hydrocephalus, 66 (55%) scans demonstrated
      noncommunicating hydrocephalus (primarily due to intraventricular hemorrhage [27
      scans, 23%] or brain tumors [24, 20%]), and 11 (9%) scans were indeterminate
      regarding whether the hydrocephalus was communicating versus noncommunicating.
      CONCLUSIONS: In a large sample of CTs performed in a rural low-income setting,
      hydrocephalus was common, predominantly noncommunicating, and often associated
      with potentially operable intracranial lesions. Data of this nature can inform
      research, policy, and clinical collaborations that strengthen the neurosurgical
      capacity of low-income countries.

PMID- 30096501
TI  - Accessing the Anterior Mesencephalic Zone: Orbitozygomatic Versus Subtemporal
      Approach.
AB  - BACKGROUND: Despite the latest developments in microsurgery, electrophysiological
      monitoring, and neuroimaging, the surgical management of intrinsic brainstem
      lesions remains challenging. Several safe entry points have been described to
      access the different surfaces of the brainstem. Knowledge of this entry zone
      anatomy is critical to performing a safe and less morbid approach. To access the
      anterior midbrain surface, a well-known entry point is the anterior mesencephalic
      (AM) zone. Our aim was to quantify surgical AM zone exposure through the
      orbitozygomatic (OZ) and subtemporal (ST) approaches. We also analyzed the
      angular exposure along the horizontal and vertical axis angles for the AM zone.
      METHODS: Ten cadaveric heads were dissected using the OZ and ST approaches for
      anterior midbrain surface exposure. A neuronavigation system was used to
      determine the 3-dimensional coordinates. The area of surgical exposure, angular
      exposure, and anatomical limits of each craniotomy were evaluated and determined
      using software analysis and compared for intersection areas and AM safe zone
      exposure. RESULTS: The median surgical exposure was 164.7 +/- 43.6 mm2 for OZ and
      369.8 +/- 70.1 mm2 for ST (P = 0.001). The vertical angular exposure was 37.7
      degrees  +/- 9.92 degrees  for the OZ and 18.4 degrees  +/- 2.8 degrees  for the
      ST opening (P < 0.001). The horizontal angular exposure to the AM zone was 37.9
      degrees  +/- 7.3 degrees  for the OZ and 47.0 degrees  +/- 3.2 degrees  for the
      ST opening (P = 0.002). CONCLUSIONS: Although the OZ craniotomy offers reduced
      surgical exposure, it provides a better trajectory to the AM zone compared with
      the ST approach.

PMID- 30096502
TI  - Effects of Increased Intracranial Pressure Gradient on Cerebral Venous Infarction
      in Rabbits.
AB  - BACKGROUND: Cerebral venous infarction (CVI) is a rare vascular disease most
      commonly caused by cerebral venous thrombosis that leads to hemorrhage or infarct
      formation. A rabbit model of CVI was established by placing a recoverable
      epidural sacculus to research effects of increased pressure on CVI. METHODS:
      Rabbits were randomly divided into the following groups: A, CVI; B, 0.2-mL
      epidural sacculus placed on the basis of CVI; C, 0.4-mL epidural sacculus; D, 0.6
      mL epidural sacculus; E, sham operation. Two sacculus-release groups were then
      added, 8 hours (group F) and 24 hours (group G), on the basis of group D. Brain
      water content, extent of cerebral infarction, hemorheology indexes, D dimer, and
      fibrinogen were observed at 8, 24, and 48 hours after surgery. RESULTS: Brain
      water content was higher in groups A-D compared with group E with the exception
      of the 24-hour A group. Brain water content was significantly lower in sacculus
      release groups compared with the 48-hour D group. Extent of cerebral infarction
      in group D was significantly higher at 24 and 48 hours compared with groups A and
      E. Extent of cerebral infarction in sacculus-release groups was significantly
      lower compared with group D at 48 hours. Hemorheology indexes and fibrinogen were
      significantly higher in group D compared with groups A and E at corresponding
      time points and increased with increasing intracranial pressure. CONCLUSIONS: In
      the rabbit model of CVI, degree of brain edema, extent of cerebral infarction,
      hemorheology indexes, and fibrinogen increased as intracranial pressure gradient
      increased, which may promote formation of a hypercoagulable state. Early removal
      of intracranial hypertension reduced degree of edema and extent of cerebral
      infarction in rabbits.

PMID- 30096503
TI  - A Rare Case of Thyrotropin-Secreting Pituitary Adenoma Coexisting with Papillary
      Thyroid Carcinoma Presenting with Visual Disturbance without Hyperthyroidism.
AB  - BACKGROUND: Thyroid-stimulating hormone-secreting pituitary adenomas (TSHomas)
      are uncommon, and majority of the patients present with symptoms of
      hyperthyroidism. Herein, we report the first case of TSHoma with differentiated
      thyroid carcinoma (DTC) that presented with visual disturbance without any
      clinical feature of hyperthyroidism. CASE DESCRIPTION: A 57-year-old man
      presented with left temporal hemianopsia of his left eye without any sign of
      hyperthyroidism. A mass lesion in the sellar and suprasellar region compressing
      the optic nerves was identified via magnetic resonance imaging. Free thyroxine
      and free triiodothyronine levels were slightly elevated, whereas the serum level
      of thyroid-stimulating hormone remained within normal range. Further
      endocrinologic examination led to the preoperative diagnosis of TSHoma.
      Ultrasonography and 111In-octreotide scan showed a mass lesion in left lobe of
      the thyroid gland, and subsequent thyroid aspiration biopsy confirmed the
      diagnosis of papillary thyroid carcinoma. After administration of short-acting
      octreotide to prevent thyrotoxic crisis in the perioperative period, the tumor
      was removed via endoscopic transnasal-transsphenoidal surgery, and the pathologic
      diagnosis of TSHoma was made. His visual acuity improved, and free
      triiodothyronine and free thyroxine levels normalized. He underwent thyroidectomy
      3 months later after endoscopic transnasal-transsphenoidal surgery. CONCLUSIONS:
      Herein, we report the first case of TSHoma with DTC that presented with visual
      disturbance without any clinical feature of hyperthyroidism and reviewed the 13
      reported cases of TSHoma coexisting with DTC. The optimal treatment strategy in
      patients with TSHoma and coexistent DTC has not been established, and
      individualized therapeutic strategies are needed.

PMID- 30096504
TI  - Endoscopic Endonasal Transclival Approach to Tumors of the Clivus and Anterior
      Region of the Posterior Cranial Fossa: An Anatomic Study.
AB  - OBJECTIVE: To present the basic topographic and anatomic features of the clivus
      and adjacent structures with an objective of possible improvements and
      optimization of the extended endoscopic endonasal posterior (transclival)
      approach when removing tumors of the clivus and anterior regions of the posterior
      cranial fossa. MATERIALS AND METHODS: A craniometric study was conducted on 125
      human skulls. A topographic anatomic study was conducted on 25 cadaver head
      specimens with arterial and venous beds stained with colored silicone, according
      to the method developed by us, to visualize its features and individual
      variability. RESULTS: The most important anatomic features of the external and
      internal regions of the clivus and the adjacent neural and vascular structures
      were analyzed. An accessible zone for the most effective transclival approach to
      the posterior cranial fossa is also specified. CONCLUSION: The endoscopic
      endonasal transclival approach can be used to obtain access to centrally located
      tumors of the posterior cranial fossa. It is an alternative to transcranial
      approaches in the surgical treatment of tumors of the clivus.

PMID- 30096505
TI  - Great Hospitals of the Russian Federation: National Medical Research Center for
      Neurosurgery Named After N. N. Burdenko: History and Contemporaneity.
AB  - In 1929 the surgeon N. N. Burdenko and the neurologist V. V. Kramer founded the
      first neurosurgical clinic in Moscow, which gained the status of Neurosurgery
      Institute in 1932. It went through a difficult path of military and peaceful
      years, overcoming all kinds of obstacles. It was constantly developed, built, and
      upgraded as it evolved to the National Medical Research Center for Neurosurgery.
      The history of the center is reviewed in this article, highlighting the notable
      personalities that have influenced the development of neurologic surgery and its
      scientific background in the Russian Federation.

PMID- 30096506
TI  - Effects of Posterior Fossa Decompression in Patients with Hunt and Hess Grade 5
      Subarachnoid Hemorrhage After Endovascular Trapping of Ruptured Vertebral Artery
      Dissecting Aneurysms.
AB  - BACKGROUND: A ruptured vertebral artery dissecting aneurysm (VADA) with a high
      clinical grade (Hunt and Hess grade 5) has a devastating prognosis. Because of
      the high rebleeding rate and location, rapid mortality can occur in patients
      owing to brainstem compression. Adjuvant decompression of the posterior fossa
      after securing the aneurysm may improve the outcomes of these patients. METHODS:
      Between January 2011 and December 2016, 22 patients who presented with Hunt and
      Hess grade 5 ruptured VADA underwent endovascular treatment. Patients were
      divided into 2 groups: group 1 (n = 12) received conventional endovascular
      treatment of VADA and external ventricular drainage, and group 2 (n = 10)
      received external ventricular drainage and suboccipital craniectomy for posterior
      fossa decompression after rapid endovascular trapping of VADA. RESULTS: In group
      2, the survival rate and good clinical outcome rate (modified Rankin scale score
      <=2) were 80% and 60%, respectively, which were favorable to the corresponding
      rates in group 1 (66.67% and 16.67%). Moreover, 80% of patients (8/10) in group 2
      regained consciousness compared with 50% of patients in group 1. CONCLUSIONS:
      Adjuvant decompression of the posterior fossa can improve outcomes in patients
      with Hunt and Hess grade V ruptured VADA.

PMID- 30096508
TI  - Growth of a Sacral Perineural (Tarlov) Cyst: Clinical Images.
AB  - Although Tarlov cysts (TC) were first described in 1938, our understanding of
      these common spinal lesions remains poor. As TCs represent incidental findings in
      the vast majority of cases, evidence to guide their management is limited to
      small case series. When they are symptomatic, the presentation can have
      significant overlap with degenerative spine disease. This is the first report
      demonstrating growth of TCs. The patient underwent open surgical reduction of the
      symptomatic TCs, leading to improvement in her symptoms.

PMID- 30096507
TI  - Intradural Juvenile Xanthogranuloma with Involvement of Multiple Nerve Roots: A
      Case Report and Review of the Literature.
AB  - BACKGROUND: Juvenile xanthogranuloma (JXG) is a rare, non-Langerhans cell
      histiocytic disorder that primarily presents as multiple cutaneous lesions in
      young males. Solitary lesions in the spinal column are an especially rare
      presentation of this disease, and central nervous system involvement can portend
      a poor prognosis. We report an unusual case of an adult woman with an
      unresectable JXG of the lumbar spine. A review of the reported cases of
      thoracolumbar JXG and the current data regarding diagnosis and treatment are
      presented. CASE DESCRIPTION: A 28-year-old woman presented with back pain and
      worsening lower extremity pain, numbness, and weakness. Magnetic resonance
      imaging demonstrated an enhancing lumbar mass. However, at surgery, no discrete
      mass was identified. Multiple roots were grossly enlarged, and electrical
      stimulation identified the L4 root with the most abnormal findings. Despite an
      attempt at debulking, most of the mass could not be safely removed. The patient
      experienced incomplete improvement of the symptoms postoperatively but elected to
      forgo chemotherapy. The 3-month follow-up imaging study showed active lumbar
      spinal disease, and imaging and follow-up examinations at 27 months revealed no
      changes. Her symptoms were satisfactorily controlled with conservative therapy.
      CONCLUSIONS: JXG of the spine is a rare disease with nonspecific clinical and
      radiographic findings that can make it difficult to diagnose and dictates the use
      of immunohistochemical staining. If possible, total surgical resection will offer
      the best outcomes; however, other modalities such as chemotherapy can be viable
      alternatives or adjuvant modalities.

PMID- 30096509
TI  - Adrenomedullin Reduces Secondary Injury and Improves Outcome in Rats with Fluid
      Percussion Brain Injury.
AB  - OBJECTIVE: Traumatic brain injury (TBI) is a devastating neurologic injury and
      remains a major cause of death in the world. Secondary injury after TBI is
      associated with long-term disability in patients with TBI. This study evaluated
      adrenomedullin (AM) on secondary injury and neurologic functional outcome in rats
      after TBI. METHODS: Forty-eight Sprague Dawley rats were randomly assigned into 3
      groups: sham, TBI, and TBI with AM groups. TBI was induced by fluid percussion
      injury, and AM was intravenously injected. Neurologic function was examined at 2,
      3, and 7 days after TBI. Enzyme-linked immunosorbent assay was used to test tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-8 levels in the
      brain. Brain edema and blood-brain barrier (BBB) permeability in brain tissue
      were tested. Western blot was used to examine the expression of aquaporin-4,
      phosphorylated myosin light-chain, and cleaved caspase-3. Terminal
      deoxynucleotidyl transferase dUTP nick end labeling was used to test the
      apoptosis. RESULTS: Compared with the sham group, TNF-alpha, IL-1beta, and IL-6
      levels, brain edema, BBB permeability, neurologic examination scores, terminal
      deoxynucleotidyl transferase dUTP nick end labeling-positive cells, and
      expression of aquaporin-4, phosphorylated myosin light-chain, and cleaved caspase
      3 significantly increased in the TBI group. AM treatment significantly inhibited
      TBI-induced effects. CONCLUSIONS: AM can improve neurologic function and
      ameliorate brain injury in rats with TBI. AM exerts its neuroprotective effect
      via its anti-inflammatory and antiapoptotic effect.

PMID- 30096510
TI  - Smartphones and mobile applications (apps) in clinical nursing education: A
      student perspective.
AB  - BACKGROUND: Nurse educators are exploring how mobile technology can support
      students in clinical practice. However, the view of nursing students on the use
      of smartphones and mobile applications (apps) to enhance clinical education has
      not been explored. Their opinions are vital to capture if the right technology is
      to be designed, evaluated, implemented and used. METHOD: A self-reported
      questionnaire, based on a review of the literature, was used to understand the
      opinions of undergraduate nursing students towards the use of smartphones and
      mobile apps to support learning in clinical environments. Descriptive statistics
      were utilised to describe participants and the mobile devices and apps they
      currently use. Thematic analysis was employed to code open-ended questions and
      explore students' perspective on how mobile apps can support learning and how
      best to implement and use them in practice. RESULTS: Two hundred nursing students
      across a four-year Bachelor of Nursing programme responded to the questionnaire.
      Most reported owning a smartphone but just under half used mobile apps to help
      them learn in clinical practice. A range of educational apps such as calculators,
      drug reference guides and medical dictionaries were used with varying frequency.
      Nursing students reported numerous benefits of mobile technology such as better
      access to educational material, improvements in knowledge and confidence, and
      reduced levels of anxiety around learning in practice. Barriers such as negative
      attitudes of nursing staff, poor Wi-Fi connectivity, and the quality of
      educational content available on mobile apps were identified as some of the
      issues preventing the adoption of mobile learning in clinical nursing education.
      CONCLUSIONS: Nursing students have a unique perspective on how smartphones and
      mobile apps can support learning in clinical practice. Nursing faculty need to
      undertake more rigorous research to determine if mobile technology can improve
      learning outcomes, how best to personalise mobile apps to students needs and
      ensure both hardware devices and educational software can be integrated in
      practice to support clinical training.

PMID- 30096511
TI  - Prevalence and significance of anti-phosphatidylserine antibodies: A pooled
      analysis in 5992 patients.

PMID- 30096512
TI  - Effects of postmortem time and storage fluid on the material properties of bovine
      liver parenchyma in tension.
AB  - In motor vehicle collisions (MVCs), liver injuries are one of the most frequently
      reported types of abdominal organ trauma. Although finite element models are
      utilized to evaluate the risk of sustaining an abdominal organ injury in MVCs,
      these models must be validated based on biomechanical data in order to accurately
      assess injury risk. Given that previous studies that have quantified the tensile
      failure properties of human liver parenchyma have been limited to testing at 48 h
      postmortem, it is currently unknown how the material properties change between
      time of death and 48 h postmortem. Therefore, the objective of this study was to
      quantify the effects of postmortem degradation on the tensile material properties
      of bovine liver parenchyma with increasing postmortem time when stored in DMEM or
      saline. A total of 148 uniaxial tension tests were successfully conducted on
      parenchyma samples of fourteen bovine livers acquired immediately after death.
      Liver tissue was submerged in DMEM or saline and kept cool during sample
      preparation and storage. Twelve livers were stored as large blocks of tissue,
      while two livers were stored as small blocks and slices. Tension tests were
      performed on multiple dog-bone samples from each liver at three time points: ~6
      h, ~24 h, and ~48 h postmortem. The data were then analyzed using a Linear Mixed
      Effect Model to determine if there were significant changes in the failure
      stress, failure strain, and modulus with respect to postmortem time. The results
      of the current study showed that the failure strain of bovine liver parenchyma
      decreased significantly between 6 h and 48 h after death when stored as large
      blocks in saline and refrigerated. Conversely, neither the failure stress nor
      failure strain changed significantly with respect to postmortem time when stored
      as large blocks in DMEM. The modulus did not change significantly with respect to
      postmortem time for tissue stored as large blocks in either saline or DMEM.
      Cellular disruption increased with postmortem time for tissue stored as large
      blocks, with tissue stored in saline showing the greatest increase at each time
      point. In addition, preliminary results indicated that reducing the tissue
      storage size had a negative effect on the material properties and cellular
      architecture. Overall, this study illustrated that the effects of postmortem
      liver degradation varied with respect to the preservation fluid, storage time,
      and storage block size.

PMID- 30096513
TI  - Mechanical characterisation of brain tissue up to 35% strain at 1, 10, and 100/s
      using a custom-built micro-indentation apparatus.
AB  - Understanding the behaviour of soft tissues under large strains and high loading
      rates is crucial in the field of biomechanics in order to investigate tissue
      behaviour during pathological processes such as traumatic brain injury (TBI). It
      is, therefore, necessary to characterise the mechanical properties of such
      tissues under large strain and high strain rates that are similar to those
      experienced during injury. However, there is a dearth of large strain and high
      rate mechanical properties for brain tissue. This is likely driven by the lack of
      commercially available equipment to perform such tests and the difficulties
      associated with developing appropriate custom-built apparatus. Here, we address
      this problem by presenting a novel, custom-built micro-indentation apparatus that
      is capable of characterising the mechanical properties of brain tissue up to 35%
      at 100/s with a spatial resolution of 250 um. Indentations were performed on the
      cortex and cerebellum of five-week-old mouse brains up to 35% strain at 1, 10,
      and 100/s. Three hyperelastic models were fitted to the experimental data that
      demonstrate the strong rate-dependency of the tissue. The neo-Hookean shear
      modulus for the cortex tissue was calculated to be 2.36 +/- 0.46, 3.64 +/- 0.48,
      and 8.98 +/- 0.66 kPa (mean +/- SD) for 1, 10, and 100/s, respectively.
      Similarly, the cerebellum shear modulus was calculated to be 1.12 +/- 0.26, 1.58
      +/- 0.32, 3.10 +/- 0.70 kPa for 1, 10, and 100/s, respectively. Student's t-tests
      were used to show statistically significant differences between the cortex and
      cerebellum at each strain rate. Furthermore, we discuss the apparent strain
      softening effect in the 100/s force-displacement curves for both regions after
      approximately 30% strain.

PMID- 30096514
TI  - Characterization of the xanthine oxidase inhibitory activity of alk(en)yl phenols
      and related compounds.
AB  - The inhibitory activity of xanthine oxidase (XO) is a combination of uric acid
      formation inhibition and superoxide anion (O2-) generation suppression. The
      inhibition of uric acid formation by XO is useful for the screening of natural
      compounds that prevent gout, while the suppression of O2- generation is useful
      for treating oxidative stress. Many edible plants contain abundant phenolic
      compounds and alk(en)yl phenols, and some of these compounds display XO
      inhibitory activity. This review focuses on XO inhibitory activity since this
      activity is used to characterize natural products. Recently, it was demonstrated
      that the inhibitory activity could be characterized using assays for XO
      inhibition, the suppression of O2- generation, DPPH radical scavenging and O2-
      radical scavenging. The inhibitory activity was divided three reaction types. The
      first is XO inhibition, the second O2- generation suppression by modification of
      enzyme molecules and the third two forms of O2- scavenging. It was demonstrated
      that these three activities are related to both the hydroxy group arrangement in
      the phenol portion and the alk(en)yl chains. This characterization is useful for
      pursuing XO inhibitors and antioxidants in natural compounds.

PMID- 30096516
TI  - Adult attachment and trust in romantic relationships.
AB  - Two theoretical perspectives guide much of the research on adult romantic
      relationships: attachment theory and interdependence theory. Each of these
      theoretical perspectives acknowledges the importance of trust, or perceptions of
      partners' dependability and faith in the future of the relationship. Whereas
      attachment theory conceptualizes trust as a component of individual differences
      in attachment representations, interdependence theoretical approaches
      conceptualize trust as a unique construct that develops within new relationships.
      In this article we discuss the importance of considering this difference in
      conceptualizations of trust for future research, highlighting the need for
      longitudinal research to properly assess the development of trust as an
      individual difference as well as uniquely within the dyadic context.

PMID- 30096515
TI  - Dimeric- and trimeric sesquiterpenes from the flower of Inula japonica.
AB  - An undescribed unusual sesquiterpene trimer and three sesquiterpene dimers were
      isolated from the flowers of Inula japonica. Their structures were elucidated by
      extensive analysis of 1D and 2D NMR spectroscopic data as well as HRESIMS data.
      Inulajaponicolide A has an undescribed carbon skeleton comprising of one
      xanthanolide and two guaianolide units with the linkage mode of C-11/C-3' and C
      11'/C-1'' via a Diels-Alder cycloaddition reaction. Inulajaponicolides C and D
      exhibited moderate cytotoxic activity against A 549 and NCI-H460 human cancer
      cell lines with IC50 values ranging from 8.5 to 17.8 MUM. Inulajaponicolides A-D
      and lineariifolianoid A possessed significant inhibitory potency against nitric
      oxide production in LPS-induced RAW264.7 cells with IC50 values ranging from 1.0
      to 4.1 MUM.

PMID- 30096517
TI  - Quadratus lumborum block is not effective for anterior cutaneous nerve entrapment
      syndrome.

PMID- 30096518
TI  - The relationship between end-expired carbon dioxide tension and severity of
      venous air embolism during sitting neurosurgical procedures - A contemporary
      analysis.
AB  - STUDY OBJECTIVE: Determine if changes in expired carbon dioxide tension correlate
      with the severity of venous air embolism (VAE) associated hemodynamic changes in
      humans. DESIGN: Retrospective case series. SETTING: A single academic medical
      center with high-volume neurosurgical practice. PATIENTS: One hundred forty seven
      adult patients having neurosurgical procedures performed with general anesthesia
      in the sitting position who experienced venous air embolism. INTERVENTIONS:
      Identification of documentation of venous air embolism by either precordial
      Doppler sonography or transesophageal echocardiography. MEASUREMENT:
      Retrospective determination of changes in end-expired carbon dioxide (EECO2)
      changes associated with venous air embolism. MAIN RESULTS: Greater absolute and
      relative decreases in end-expired carbon dioxide tension were associated with
      greater hemodynamic manifestations of venous air embolism. However, based on
      receiver operating characteristic curve analysis, the absolute and relative
      changes in EECO2 have moderate utility for predicting the severity of hemodynamic
      consequences of venous air embolism as area under the curve for absolute and
      relative carbon dioxide tensions were 0.7654 and 0.7263, respectively.
      CONCLUSIONS: Greater magnitude of decreases in EECO2 is associated with
      hemodynamically-significant VAE in mechanically-ventilated patients. However, the
      magnitude of changes may have limited utility to diagnose VAE or exclude the
      diagnosis of VAE in patients with unexplained intraoperative hypotension.

PMID- 30096519
TI  - Hepatotoxicity after desflurane anesthesia in a morbidly obese patient.

PMID- 30096520
TI  - Interpreting meta-analysis of ultrasound-guided vs palpation methods for radial
      artery cannulation may not fully capture differences in technique optimization.

PMID- 30096521
TI  - Novel method of securing 15 mm endotracheal tube adapter to avoid unnecessary
      tube exchange.

PMID- 30096522
TI  - Clinical experiences of pericapsular nerve group (PENG) block for hip surgery.

PMID- 30096523
TI  - Orderly-designed Ni2P nanoparticles on g-C3N4 and UiO-66 for efficient solar
      water splitting.
AB  - Stable and efficient photocatalyst is the key important research goals up to now.
      On account of the dominant performance of Ni2P, g-C3N4 (graphitized carbonitride)
      and UiO-66 (Universitetet i Oslo) themselves, an orderly-designed assemble of g
      C3N4/UiO-66/Ni2P is successfully designed and assembled with capability of high
      efficient dye-sensitized photocatalytic H2 evolution. The electron transport
      routes are successfully adjusted and the hydrogen evolution is greatly improved.
      It exhibits synergistic effect on highly efficient photocatalytic hydrogen
      production. The maximum amount of hydrogen evolution reaches about 200 MUmol for
      5 h over the g-C3N4/UiO-66/Ni2P photocatalyst under the 5 W LED white light at
      420 nm. The H2 evolution rate is 12 times high than over g-C3N4. Such
      synergistically increased effect in photocatalytic properties is certified by
      related characterization results such as TEM, SEM, XPS, XRD, UV-vis DRS,
      Transient photocurrent and FT-IR etc. The above studies show that the Ni2P
      nanoparticles modified on the g-C3N4/UiO-66 provides the more active sites and
      improves the efficiency of photo-generated charge separation. In addition, the
      possible mechanism of photocatalytic hydrogen production is proposed.

PMID- 30096524
TI  - Gravity induced fluid fragmentation in an asymmetric microfluidic Y junction.
AB  - HYPOTHESIS: In this study, the spontaneous and forced imbibition of an asymmetric
      Y junction by a completely wetting fluid submitted to the action of gravity is
      investigated. The considered junction is made of three capillaries of close but
      different dimensions. This system is used as a simple model to study gravity
      induced fluid fragmentation in microfluidic junctions and porous media. Using
      simple calculations, analytical results predict a fragmentation criterion, two
      dynamics leading to fluid fragmentation and asymptotically drop lengths and
      spacings. EXPERIMENTS: Both spontaneous and forced imbibitions of three
      microfluidic Y junctions were undertaken, varying the capillary and Bond numbers.
      Results show the validity of the fragmentation criterion, the derived junction
      imbibition dynamics and confirm qualitatively the analytical description of the
      fragmentation process. FINDINGS: The dynamics prior to fragmentation does not
      depend on whether the imbibition is forced or spontaneous. However, it depends on
      the position with respect to gravity of the junction branch of lowest Laplace
      pressure. Finally, gravity induced fragmentation happens in the squeezing regime
      described in the Drop-On-Demand (DOD) literature at the junction and is locally
      controlled by viscosity rather than gravity.

PMID- 30096525
TI  - Effects of magnetic field on the spreading dynamics of an impinging ferrofluid
      droplet.
AB  - This paper presents a comprehensive experimental study of the effects of
      vertically and horizontally applied magnetic fields on the dynamics of
      magnetowetting and the formation of satellite droplet. Besides explaining the
      physics of the transient variation of different drop shape parameters, the role
      of a magnetic field on controlling the dynamics of spreading is also presented.
      Ultimately the magnetic field maneuvers the droplet spreading without altering
      the surface chemistry. The morphological evolution and dynamics of an impacting
      ferrofluid droplet has also been studied. By observing the spreading at an
      appropriate time scale, the contrary spreading behavior of the paramagnetic
      ferrofluid under the effect of magnetic field is noticed. Special attention is
      given to the droplet break-up and satellite droplet formation. A universal
      relationship is presented between the drop shape parameters before and after the
      impact. The destination and travel path of the satellite droplet is also analyzed
      in a vertical as well as horizontal magnetic field, which governs the satellite
      droplet merging with the already deposited parent droplet.

PMID- 30096526
TI  - Temperature dependent photocatalysis of g-C3N4, TiO2 and ZnO: Differences in
      photoactive mechanism.
AB  - Photocatalysis has been believed as one of the green and sustainable avenues to
      address energy and environmental crises by converting solar energy to chemical
      energy via reactions. Temperature is usually a vital factor controlling kinetics
      and thermodynamics of a reaction, but it has been less investigated in
      photocatalysis. In this work, the effect of reaction temperature on
      photocatalysis was investigated in a simple process, photocatalytic degradation
      of Congo Red (CR) on three typical catalysts, g-C3N4, TiO2 and ZnO, to
      differentiate the interfacial radical generation and reaction mechanism. The
      results showed that the temperature has a positive effect on the photocatalytic
      activity of the three catalysts. The scavenger experiments at various
      temperatures indicated that the generation of reactive species from the three
      photocatalysts is different and that the free radicals can be produced more
      quickly at higher temperatures, causing improved activities in photocatalysis.
      However, photocurrent analysis and EIS at various temperatures showed that the
      temperature had a different effect on recombination rate and transfer barriers of
      the charge carriers from each catalyst. Therefore, the dramatic enhancement in
      photodegradation activities probably originated from a novel mechanism of the
      photothermocatalytic oxidation. The interfacial reaction and mechanism from the
      influence of reaction temperature on the photocatalytic process was proposed.

PMID- 30096527
TI  - Facile fabrication of a biomass-based film with interwoven fibrous network
      structure as heterogeneous catalysis platform.
AB  - The stable and efficient immobilization of silver nanoparticles (AgNPs) on/into
      processable biomass-based macro-support with porous networks is a promising and
      sustainable strategy to achieve both high catalytic activity and excellent
      reusability for heterogeneous catalysis. In this work, a collagenic composite
      film was facilely fabricated at room temperature, via the self-assembly of
      natural collagen fibers (CFs) and gallic acid modified silver nanoparticles
      (GA@AgNPs) induced by chromium (III) cross-linking in water. The morphology and
      microstructure of such GA@AgNPs-Cr-CFs composite film was investigated by
      Scanning Electron Microscope (SEM) and X-ray Photoelectron Spectroscopy (XPS),
      respectively. The results revealed that the cross-linking based on the
      coordinated complexation between chromium ions (Cr3+) and carboxyl groups on CFs
      and GA@AgNPs played the critical role in the interwoven of collagen fibers,
      leading to a three dimensional (3D) interconnected porous network of the
      composite film with simultaneously incorporation and high payload of silver
      nanoparticles. Furthermore, this GA@AgNPs-Cr-CFs composite film exhibited
      excellent catalytic activity toward the reduction of 4-nitrophenol (4-NP), taking
      the advantage of its high specific surface area given by the interwoven fibrous
      network structure. More than that, such sustainable composite catalyst could be
      easily recovered and reused for ten cycles because of its high stability based on
      cross-linking. This catalytic platform constructed by natural fibers, noble metal
      nanoparticles and trivalent metal ions showed a sustainable avenue for
      heterogeneous catalytic system.

PMID- 30096528
TI  - Fabrication of electrospun trace NiO-doped hierarchical porous carbon nanofiber
      electrode for capacitive deionization.
AB  - Trace nickel oxide-embedded hierarchical porous carbon nanofibers (CNF-NiO) were
      fabricated by electrospinning polyacrylonitrile-Ni(NO3)2 (PAN-Ni) followed by
      stabilization, carbonization and acid treatment. The resultant CNF-NiO was
      characterized by scanning electron microscopy, transmission electron microscopy,
      X-ray photoelectron spectroscopy, thermo gravimetric analysis and nitrogen
      adsorption-desorption isotherm. The NiO amount and porous structure can be tuned
      by varying the PAN/Ni ratio and acid treatment time. The electrochemical
      properties of the electrospun CNF-NiO nanofibers were analyzed by cyclic
      voltammetry and impedance method. The specific capacity of 157.9 F/g was obtained
      at the PAN/Ni mass ratio of 90:3 with 3 h HCl wash. This porous CNF-NiO composite
      has been applied as a self-supporting cathode for capacitive deionization. The
      desalination amount arrived at 6.2 mg/g, which is 3 times as high as that of the
      electrospun pure carbon fibers. Longer wash time leads to decreased capacitance
      and desalination performance.

PMID- 30096529
TI  - 1D ultrafine SnO2 nanorods anchored on 3D graphene aerogels with hierarchical
      porous structures for high-performance lithium/sodium storage.
AB  - SnO2 is considered as one of the most promising alternative anode materials for
      lithium ion batteries (LIBs) and sodium ion batteries (SIBs) due to high specific
      capacity, low discharge voltage plateau and environmental friendliness. In this
      work, 1D ultrafine SnO2 nanorods anchored on 3D graphene aerogel (SnO2 NRs/GA)
      composite is prepared through a simple reduction-induced self-assembly method in
      the solution of graphene oxide (GO), Vitamin C and SnO2 nanoparticles. Vitamin C
      plays an important role in the reduction of GO. The structural and morphological
      characterizations demonstrate that 1D ultrafine SnO2 nanorods are uniformly and
      tightly anchored on the surface of 3D graphene nanosheet aerogels. The unique 3D
      network structure as well as the synergistic effect between 3D graphene nanoshhet
      and 1D SnO2 nanorods endows the as-prepared SnO2 NRs/GA composite with the good
      electrochemical lithium/sodium storage performance. It delivers the high initial
      discharge capacity (1713 mA h g-1 at 0.1 A g-1 for LIBs and 539 mA h g-1 at 0.05
      A g-1 for SIBs) and good cycle stability (869 mA h g-1 at 0.1 A g-1 after 50
      cycles for LIBs and 232 mA h g-1 at 0.05 A g-1 after 100 cycles for SIBs).
      Moreover, the SnO2 NRs/GA composite exhibits excellent cycle stability for SIBs
      with a high reversible capacity of 96 mA h g-1 at as high as 1 A g-1 for 500
      cycles. This work provides a simple method to fabricate the electro-active
      materials-graphene aerogel composites for high-performance LIBs and SIBs.

PMID- 30096530
TI  - Coalescence of charged droplets in outer fluids.
AB  - A controlled technique to produce a precise volume of fluid species, such as
      water droplets, has critical importance in a variety of industrial applications.
      Electric field provided a well-established method to produce charged water
      droplets with a controlled volume. The coalescence of produced charged water
      droplets, however, impedes the efficiency of electric field-assisted methods.
      Whereas the coalescence of stationary single droplets, often charged, is
      overwhelmingly studied in air or vacuum, the effects of surrounding medium and
      approaching velocity are neglected. Systematic series of experiments and
      simulations were designed to address the effect of viscosity as well as
      approaching velocity on the coalescence of charged water droplets in viscous
      surrounding mediums (MU = 100 & 1000 cSt). Results suggested that increasing the
      electrical conductivity of water droplets with lower approaching velocity
      diminishes the chance of coalescence between water droplets. The higher viscosity
      of surrounding medium resulted in a lower chance of coalescence between water
      droplets while droplets with stronger electrical conductivities underwent a lower
      deformation inside the dielectric medium. Finally, results suggested that water
      chain formation, which is reportedly a main retarding factor in
      electrocoalescers, took place for droplets with intermediate sizes in higher
      viscosities of surrounding medium.

PMID- 30096531
TI  - Bismuth oxyfluoride/bismuth oxyiodide nanocomposites enhance visible-light-driven
      photocatalytic activity.
AB  - This is the first paper to report a series of bismuth oxyfluoride/bismuth
      oxyiodide (BiOpFq/BiOxIy) nanocomposites with different F/I molar ratios, pH
      values, and reaction temperatures that were synthesized through a template-free
      and controlled hydrothermal method. These nanocomposites were characterized
      through scanning electron microscope energy dispersive microscopy (SEM-EDS),
      transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier
      transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), Brunauer
      Emmett-Teller (BET), and diffuse reflectance spectroscopy (DRS). Under visible
      light irradiation, the BiOpFq/BiOxIy composites exhibited excellent
      photocatalytic activities in the degradation of crystal violet (CV) and 2
      hydroxybenzoic acid (HBA). The order of rate constants was BiOF/BiOI > BiOI ?
      BiOF. The photocatalytic activity of BiOF/BiOI composites reached a maximum rate
      constant of 0.2305 h-1, 1.2 times higher than that of BiOI and 100 times higher
      than that of BiOF. Thus, the derived BiOF/BiOI is crucial for photocatalytic
      activity enhancement. After the removal of CV in the third cycle, no apparent
      deficits in photocatalytic activity were observed, and the observed deficit was
      8.2% during the fifth run. Overall, the catalytic activity and stability observed
      for the proposed composites were determined to be adequate under visible-light
      irradiation. For various scavengers, the noted quenching effects demonstrated
      that reactive O2- has a notable role in the degradation of the applied CV.

PMID- 30096532
TI  - Low-temperature electrospray-processed SnO2 nanosheets as an electron
      transporting layer for stable and high-efficiency perovskite solar cells.
AB  - Semiconducting metal oxide electron transporting layers (ETLs) with distinct
      morphologies have the ability to produce the less-hysteric and high efficiency
      perovskite solar cells (PSCs). Here, for the first time we introduce a viable
      electrospraying route for one-step deposition of highly mesoporous SnO2
      nanosheets, as the ETLs in PSCs with reduces hysteresis, high charge collection
      efficiency and improved ambient stability. Furthermore, optimization of the
      interfacial properties between the SnO2 nanosheets and the perovskite absorber
      layer by the employment of a C60 interlayer consequences in decreasing the charge
      recombination, better energy level alignment, and significantly improved power
      conversion efficiency (PCE). Consequently, the efficient PSCs based on C60
      modified SnO2 nanosheets ETLs have almost hysteresis-free behavior, with a best
      PCE of 20.2% thanks to the highly porous nature of nanosheets and better
      perovskite infiltration. This study reveals that hierarchical SnO2 is a possible
      ETL for producing low-cost and efficient PSCs with long-term stability.

PMID- 30096533
TI  - IgG4-related disease mimicking pancreatic cancer: Case report and review of the
      literature.
AB  - INTRODUCTION: Most patients with pancreatic masses pose a diagnostic challenge
      when a benign lesion is suspected, and often, resection is needed before a benign
      diagnosis is confirmed. PRESENTATION OF CASE: A 57 years old male patient
      presented with a pancreatic head mass, obstructive jaundice and submandibular
      lymph node enlargement. He also had a history of recurrent eye pain and redness,
      skin lesions, and benign prostatic hypertrophy. MRI showed a pancreatic head mass
      with double duct sign, aortic thickening, bilateral renal lesions, diffuse lymph
      node enlargement, and prostatic enlargement. FDG-PET/CT demonstrated abnormal
      uptake corresponding to the MRI lesions, and there were elevated IgG4 levels on
      blood investigations. Biopsy of an inguinal lymph node revealed infiltrates with
      IgG4 plasma cells, consistent with the diagnosis of IgG4 disease. The patient was
      treated with IV steroids and showed significant improvement. DISCUSSION: IgG4
      related disease is a rare entity that is characterized by lesions that show heavy
      infiltration with IgG4 positive plasma cells, storiform fibrosis, and
      obliterative phlebitis. The pancreas is the most commonly involved organ, but
      several other organ systems are involved, and this helps in clinical suspicion of
      the diagnosis. A biopsy from any easily accessible site that shows the
      characteristic histological features is sufficient for diagnosis. Patients
      respond quickly to steroids, but recurrence is frequent. CONCLUSION: IgG4 related
      disease is a rare cause of pancreatic tumorous lesions that need a high index of
      suspicion for diagnosis and should be differentiated from pancreatic neoplastic
      lesions.

PMID- 30096534
TI  - Laparoscopic relief of reduction en masse followed by elective preperitoneal
      inguinal hernia repair with Modified KugelTM Patch.
AB  - INTRODUCTION: Reduction en masse is a rare complication of inguinal hernia. This
      condition is defined as the displacement of a strangulated hernia mass into the
      preperitoneal space. CASE PRESENTATION: A 62-year-old man presented with severe
      abdominal pain after a forcible reduction of an incarcerated right inguinal
      hernia. Abdominal computed tomography (CT) scan suggested strangulated bowel.
      Emergency exploratory laparoscopy was performed and the incarcerated bowel was
      successfully released. Elective preperitoneal inguinal hernia repair using the
      Modified KugelTM Patch was performed under laparoscopic guidance. The patient
      made an uneventful recovery. DISCUSSION: Reduction en masse should be considered
      when abdominal pain persists after a difficult reduction of inguinal hernia.
      Laparoscopic guidance led to the definitive repair of the inguinal hernia with
      reduction en masse. CONCLUSION: Laparoscopic relief can be an efficient
      therapeutic option for the management of this condition. In addition, Modified
      KugelTM Patch repair with ligation of the hernia sac could be a reasonable
      treatment.

PMID- 30096535
TI  - Copper or/and arsenic induces autophagy by oxidative stress-related PI3K/AKT/mTOR
      pathways and cascaded mitochondrial fission in chicken skeletal muscle.
AB  - Autophagy is an ubiquitin proteasome system for degradation of intracellular
      damaged proteins and organelles. Both as environmental pollutants, flourishing
      data show arsenic (As) and copper (Cu) as robust oxidative stress inducers.
      Whether this kind of damage correlates with autophagy through the
      phosphoinositide-3-kinase/protein kinase b/mammalian target of rapamycin
      (PI3K/AKT/mTOR) pathway still remains elusive. A 12-week exposures of Cu or/and
      As to chicken time-dependently displayed significant element residue in the
      pectoralis. Aligning with previous results, a strong pro-oxidant nature of Cu and
      As was clearly indicated by enzyme/nonenzyme antioxidants. Fragmented
      mitochondria induced by oxidative damage were accompanied by overexpressed
      dynamin related protein-1 and decreased mitochondrial fusion-related genes. Upon
      comparative analysis, time-dependent conversion of light chain 3 (LC3)-I to LC3
      II, increases in autophagy-related genes such as Bcl-2-interacting protein
      (Beclin-1) and inhibited PI3K/AKT/mTOR pathway firmly supported the fact that Cu
      or/and As induces autophagy. These results further coincided with ultrastructure
      showing clusters of vesicles and autophagosome in the skeletal muscle.
      Interestingly, the time-dependently elevated heat shock proteins observed in Cu
      or/and As treated chicken suggest the continuous adaptation and physiological
      acclimation of organisms to this stress responses. Interestingly, the combination
      of copper and arsenic elicited more serious oxidative damage and its-cascaded
      injuries than their individuals. Together, our results showed that after Cu
      or/and As insult and accumulation, inhibited PI3K/AKT/mTOR pathway activated
      autophagy and disturbed mitochondrial dynamic, forming a positive feedback with
      redox disorder.

PMID- 30096537
TI  - Study on effect of laser-induced ablation for Lamb waves in a thin plate.
AB  - In this paper, the effect of ablation on the shape of elastic waves generated by
      laser excitation is studied numerically and experimentally. Laser-induced
      ultrasound has been widely used in the nondestructive testing (NDT) field because
      it has the advantage that the sensor does not have to be directly attached to the
      target structure. In the safety assessment process, low energy excitation is
      used, and thus the structure is not damaged. Most studies related to laser
      ultrasound have focused on the method of detecting cracks within the elastic
      range, and there have been few studies on the effect of ablation. This research
      consists of experiments and numerical analyses. In experiments, elastic waves
      were generated in an aluminum plate by projecting laser pulses with different
      energy intensities. The velocities in the thickness direction were measured using
      a Laser Doppler Velocimeter (LDV) at a point 135 mm away from the excitation
      point. In the numerical study, two numerical simulations were carried out using
      heat flux and normal stress input to mimic laser pulse excitation. A thermo
      mechanical simulation by heat flux was conducted to simulate thermal expansion by
      the laser pulse, and the normal stress was applied to reflect the effect of
      radiation pressure by ablation, respectively. Waveforms were synthesized by using
      different magnitude ratios of the obtained numerical responses and were compared
      with the experiment results. It is found that the effect of radiation pressure
      should not be neglected if the energy intensity is large although the effect of
      radiation pressure decreases as the energy intensity decreases. At the energy
      intensity with which ablation occurs, the effects of thermal expansion and
      radiation pressure exist simultaneously, and the contribution to the response
      depends on the energy intensity.

PMID- 30096538
TI  - Predictors of residency status in chronically institutionalized and community
      dwelling schizophrenia patients.
AB  - BACKGROUND: This cross-sectional study contrasted chronically hospitalized
      schizophrenia (SZ) spectrum disorder inpatients to SZ community dwelling patients
      on measures of psychopathology, social competence, neuropsychological performance
      and real-world functioning in order to discern factors predictive of patients'
      residency status and to characterize the contrasting ends of the SZ outcome
      continuum. METHOD: Subjects included 26 chronic SZ patients hospitalized
      continuously on average for 12.8 years, and 26 SZ patients with a history of at
      least 18 months tenure in community placement. RESULTS: A series of multivariate
      analyses revealed both chronically hospitalized and community dwelling patients
      were similar in terms of their real world functioning abilities such as work
      skills, interpersonal skills, self-care skills and community engagement. Chronic
      SZ inpatients' manifested more severe functional competency and neurocognitive
      deficits relative to outpatients. Additionally, chronic inpatients were
      discriminated from community dwelling outpatients by their symptom severity and
      commitment of more socially undesirable/antisocial type behaviors. CONCLUSIONS:
      Factors associated with chronic institutionalization are, in part, related to
      commission of antisocial type behaviors, as well as poor social and
      neurocognitive competences, and total symptom severity rather than deficits in
      everyday functional abilities.

PMID- 30096536
TI  - Calcium release-activated calcium channels and pain.
AB  - Calcium release-activated calcium (CRAC) channels are unique among ion channels
      that are activated in response to depletion of intracellular calcium stores and
      are highly permeable to Ca2+ compared to other cations. CRAC channels mediate an
      important calcium signal for a wide variety of cell types and are well studied in
      the immune system. They have been implicated in a number of disorders such as
      immunodeficiency, musculosketal disorders and cancer. There is growing evidence
      showing that CRAC channels are expressed in the nervous system and are involved
      in pathological conditions including pain. This review summarizes the expression,
      distribution, and function of the CRAC channel family in the dorsal root
      ganglion, spinal cord and some brain regions, and discusses their functional
      significance in neurons and glial cells and involvement in nociception and
      chronic pain. Although further studies are needed to understand how these
      channels are activated under physiological conditions, the recent findings
      indicate that the CRAC channel Orai1 is an important player in pain modulation
      and could represent a new target for pathological pain.

PMID- 30096539
TI  - Molecular mechanisms governing the evolutionary conservation of Glycine in the
      6th position of loops IotaIotaIota and IotaV in photoprotein mnemiopsin 2.
AB  - Photoproteins in their functional form are complexed noncovalently with 2
      hydroperoxycoelenterazine. A conformational change upon coordination of Ca+2 ions
      with their EF-hand loops leads to oxidation of substrate and emission of light.
      In all photoproteins, EF-hand loops Iota, IotaIotaIota and IotaV have standard
      sequence for binding to Ca+2 ion, however the second one is not able for Ca+2
      coordination. Sequence analysis of Mnemiopsin 2 and other known photoproteins
      shows that Glutamate (Glu) is occurred in the 6th position of its first EF-hand
      loop, but this position in other loops of mnemiopsin 2 and all functional loops
      of other photoproteins is occupied by Glycine (Gly). Here we designed and made
      single and double mutants where Gly residue at the 6th positions of loops
      IotaIotaIota and IotaV of mnemiopsin 2 was replaced with Glu. According to the
      activity measurements, wild-type (WT) and G142E variants have more initial
      luminescence intensity than G176E and double mutants; while WT and G176E have
      higher values of half decay time when compared with G142E and double mutants.
      According to the isothermal denaturation experiments, all protein variants are
      structurally more stable than WT mnemiopsin 2 and that the stabilizing effects of
      single mutants are paired resulting in more stability of double mutant against
      urea denaturation. We concluded that simultaneous occurrence of Gly in the 6th
      position of loops IotaIotaIota and IotaV is essential for evolutionary adjustment
      of initial intensity and decay rate of luminescence emission via affecting the
      interaction of the core structure of photoprotein with coelenteramide and binding
      affinity of Ca+2 to the corresponding loops, respectively.

PMID- 30096540
TI  - Electrochemical synthesis, photodegradation and antibacterial properties of PEG
      capped zinc oxide nanoparticles.
AB  - The effect of surfactant and dopant on the properties of zinc oxide nanoparticles
      were studied by preparing polyethylene glycol (PEG) capped ZnO and tungsten doped
      PEG capped ZnO nanoparticles via the electrochemical method. These nanoparticles
      were characterized using X-Ray Diffraction (XRD), Fourier Transform Infrared
      Spectroscopy (FTIR), Ultraviolet Diffuse Reflection Spectroscopy (UV-DRS),
      Scanning Electron Microscopy (SEM) and Electron Dispersive Analysis of X Rays
      (EDAX). The photocatalytic degradation of malachite green dye using these
      nanoparticles was studied under visible light. The effects of various reaction
      parameters like dye concentration, catalyst concentration, pH and time were
      studied to optimize the photodegradation reaction. Reusability of these
      nanoparticles was studied and no significant change was observed in the
      degradation efficiency of PEG capped ZnO till the fourth cycle, while there was a
      gradual decrease in the degradation efficiency of tungsten doped PEG capped ZnO.
      Langmuir- Hinshelwood kinetic model well describes the photodegradation capacity
      and the degradation of malachite green follows pseudo-first order
      kinetics.Photocatalytic studies reveal that PEG capping increases the degradation
      properties of ZnO while tungsten doping decreases the extent of PEG capping and
      has a detrimental effect on the degradation properties of ZnO. The prepared
      nanoparticles exhibit significant antibacterial properties against gram-positive
      Bacillus cereus and gram-negative Escherichia coli bacterial strains by agar well
      diffusion method.

PMID- 30096541
TI  - Repeated measures of prenatal phthalate exposure and maternal hemoglobin
      concentration trends: The Ma'anshan birth cohort (MABC) study.
AB  - A prospective cohort study of a Chinese population was conducted to investigate
      the relationship between prenatal phthalates exposure and maternal hemoglobin or
      anemia. Based on the Ma'anshan Birth Cohort study, 7 phthalate metabolites were
      quantified in spot pregnancy urine samples (n = 9263) from 3269 pregnant women
      during each trimester. The maternal hemoglobin concentrations were obtained from
      electronic medical records at the same three time points for each participant
      during pregnancy. Anemia was defined as a hemoglobin concentration below 110 g/L
      in pregnant women. Repeated measures and trimester-specific analyses were used to
      estimate the effects of phthalates exposure on maternal hemoglobin and anemia.
      The prevalence of anemia was 3.6%, 27.0%, and 26.5% during the first, second and
      third trimester, respectively. Repeated measures analysis showed that hemoglobin
      concentrations decreased by 0.55, 0.19, 0.57, 0.49, and 0.54 g/L with each 1 ln
      transformed concentration increase of MBP, MBzP, MEHP, MEOHP, and MEHHP,
      respectively. Exposure to MMP, MBP, MEHP, MEOHP, and MEHHP increased the risk of
      anemia by 1.11-fold, 1.21-fold, 1.20-fold, 1.13-fold, and 1.16-fold,
      respectively. Trimester-specific regression models stratified by the sample
      collection time during pregnancy generated consistent results. This is the first
      study focusing on the effect of prenatal phthalate exposures on hemoglobin or
      anemia in pregnant Chinese women. We found that prenatal phthalates exposure not
      only decreased the concentrations of hemoglobin but also showed associations with
      the prevalence of anemia. Associations appeared stronger for the subsample
      representing women pregnant with a male fetus than those pregnant with a female
      fetus. Anemia remains a moderate public health problem in China, and effective
      measures should be implemented.

PMID- 30096542
TI  - Ambient air pollution and daily hospital admissions: A nationwide study in 218
      Chinese cities.
AB  - There have been few large multicity studies to evaluate the acute health effects
      of ambient air pollution on morbidity risk in developing counties. In this study,
      we examined the short-term associations of air pollution with daily hospital
      admissions in China. We conducted a nationwide time-series study in 218 Chinese
      cities between 2014 and 2016. Data on daily hospital admissions counts were
      obtained from the National Health Insurance Database for Urban Employees covering
      0.28 billion enrollees. We used generalized additive model with Poisson
      regression to estimate the associations in each city, and we performed random
      effects meta-analysis to pool the city-specific estimates. More than 60 million
      hospital admissions were analyzed in this study. At the national-average level,
      each 10 MUg/m3 increase in PM10, SO2, and NO2, and 1 mg/m3 increase in CO at lag
      0 day was associated with a 0.29% (95% CI, 0.23%-0.36%), 1.16% (95% CI, 0.92%
      1.40%), 1.68% (95% CI, 1.40%-1.95%), and 2.59% (95% CI, 1.69%-3.50%) higher daily
      hospital admissions, respectively. The associations of air pollution with
      hospital admissions remained statistically significant at levels below the
      current Chinese Ambient Air Quality Standards. The effect estimates were larger
      in cities with lower air pollutants levels or higher air temperatures and
      relative humidity, as well as in the elderly. In conclusion, our findings provide
      robust evidence of increased hospital admissions in association with short-term
      exposure to ambient air pollution in China.

PMID- 30096543
TI  - Foliar mercury content from tropical trees and its correlation with physiological
      parameters in situ.
AB  - The terrestrial biogeochemical cycle of mercury has been widely studied because,
      among other causes, it presents a global distribution and harmful biotic
      interactions. Forested ecosystems shows great concentrations from Hg and
      Litterfall is known as the major contributor to the fluxes at the soil/air
      interface, through the superficial adsorption on the leaves and by the gas
      exchange of the stomatal pores. The understanding of which processes control the
      stage of Hg cycle in these ecosystems is still not totally clear. The influences
      of physiological and morphological parameters were tested against the Hg
      concentrations in the leaves of 14 endemic species of an evergreen tropical
      forest in south-eastern Brazil, and an exotic species from Platanus genus.
      Pathways were studied through leaf areas and growing tree parameters, where
      maximum rate of net photosynthesis (Pnmax), transpiration rate (E), stomatal
      conductance (Gs) were examined. The results obtained in situ indicated a positive
      correlation between Pnmax and the Hg concentration; Cedrela fissilis and Croton
      floribundus were the most sensitive species to the accumulation of Hg and the
      most photosynthetically active in this study. The primary productivity from
      Tropical forest should be a proxy of Hg deposition from atmosphere to soil,
      retained there while forests stand up, representing an environmental service of
      sequestration of this global pollutant. Therefore, forests and trees with great
      photosynthetic potential should be considered in predictions, budgets and non
      geological soil content regarding the global Hg cycle.

PMID- 30096544
TI  - The response of chironomid taxonomy- and functional trait-based metrics to fish
      farm effluent pollution in lotic systems.
AB  - The lotic habitats affected by trout farm waste are colonized with a particular
      invertebrate community of which chironomids are the most abundant group. However,
      there is little information available regarding how chironomid community
      structures respond to this type of pollution at the highest taxonomic resolution.
      Eight fish farms, together with their lotic systems as recipients, were used to
      test the variability of the chironomid community and its surrogates (taxonomic
      and functional metrics) across spatially arranged sampling sites to form a
      gradual decrease in the trout farm influence. The self organizing map (SOM)
      classified six different types of chironomid communities which were
      characteristic for both the control and affected habitats. The species indicator
      analyses listed 32 taxa as positive indicators of water pollution. The SOM and
      Kruskal-Wallis test revealed that the pattern of chironomid community structure
      obtained was mainly driven by six environmental parameters (Altitude,
      conductivity, distance from the outlet, hardness, HN4-N, NO3-N). Categorical
      principal components analysis (CATPCA) derived three models for each type of
      biotic metric, in which for diversity-, taxonomy- and functional feeding group
      based metrics, the first two dimensions explained 55.2%, 58.3% and 55.4%, of the
      total variance respectively for 315 sampling sites. According to this analysis,
      the total number of taxa (S), abundance and the Shannon-Wiener index (H') (as a
      diversity metric), as well as the proportion of Tanypodinae (as taxonomic group)
      and grazers/scraper (GRA) and gatherer collector (GAT)(as FFG metrics), were
      related to the outlet distance gradient, thus showing great potential to be used
      in the multimetric approach in bioassessment.

PMID- 30096545
TI  - Influence of urbanisation characteristics on the variability of particle-bound
      heavy metals build-up: A comparative study between China and Australia.
AB  - Heavy metal pollution of urban stormwater poses potential risks to human and
      ecosystem health. The design of reliable pollution mitigation strategies requires
      reliable stormwater modelling approaches. Current modelling practices do not
      consider the influence of urbanisation characteristics on stormwater quality.
      This could undermine the accuracy of stormwater quality modelling results. This
      research study used a database consisting of over 1000 datasets to compare the
      characteristics of heavy metal build-up (one of the most important stormwater
      pollutant processes) on urban surfaces under the influence of anthropogenic and
      natural factors specific to different urban regions from China (Shenzhen) and
      Australia (Gold Coast), using Bayesian Networks. The outcomes show that the
      differences in heavy metals build-up loads between the two regions (mean value
      for Shenzhen - mean value for Gold Coast)/mean value for Shenzhen) were 0.45
      (Al), 0.88 (Cr), 0.99 (Mn), 0.68 (Fe), 0.98 (Ni), 0.24 (Cu), 0.47 (Zn) and 0.13
      (Pb), respectively. The research outcomes also confirmed that the influence of
      traffic on the build-up of different sized particles varies between Shenzhen and
      Gold Coast, and traffic plays distinct roles as a source and as a factor that
      drives heavy metal re-distribution. The road surface roughness was also found to
      influence build-up process differently between the two regions. More importantly,
      the assessment of inherent process uncertainty revealed that heavy metal build-up
      between different road sites in Shenzhen varies over a wider range than in Gold
      Coast. The study highlighted a clear distinction in the influence of sources and
      key anthropogenic factors on the variability of particle-bound heavy metals build
      up between geographically different urban regions. The study outcomes provide new
      knowledge to enhance the accuracy of urban stormwater quality modelling.

PMID- 30096546
TI  - Microplastics in the Arctic: A case study with sub-surface water and fish samples
      off Northeast Greenland.
AB  - The Arctic is a unique and fragile ecosystem that needs to be preserved and
      protected. Despite its remoteness, plastic pollution has been documented in this
      region. In the coming years, it is likely to worsen since, with climate changes
      and the opening of new shipping routes, the human presence is going to increase
      in the whole area. Here, we investigated the presence of microplastics (MPs) in
      sub-surface water and in two mid-trophic level Arctic fishes collected off
      Northeast Greenland: the demersal bigeye sculpin, Triglops nybelini, and the
      pelagic polar cod, Boreogadus saida. Plastics debris were found in the water
      samples at a concentration of 2.4 items/m3 +/-0.8 SD which is higher than in most
      seas at lower latitudes. Both fish species had eaten MPs with different
      proportion among the species, 34% for T. nybelini (n = 71) and 18% for B. saida
      (n = 85). The significant difference in the occurrence of MPs between the two
      species is likely a consequence of their feeding behavior and habitat.
      Polyethylene was the main plastic polymer for water samples (41%, n = 17) and
      polyester (34%, n = 156) for fish samples as analyzed by Fourier Transformed
      Infrared (FT-IR) spectroscopy. Our data underscore that the Arctic regions are
      turning into a hotspot for plastic pollution, and this calls urgently for
      precautionary measures.

PMID- 30096547
TI  - A comprehensive probabilistic approach for integrating natural variability and
      parametric uncertainty in the prediction of trace metals speciation in surface
      waters.
AB  - The main objectives of this study were to evaluate global uncertainty in the
      prediction of Distribution coefficients (Kds) for several Trace Metals (TM) (Cd,
      Cu, Pb, Zn) through the probabilistic use of a geochemical speciation model, and
      to conduct sensitivity analysis in speciation modeling in order to identify the
      main sources of uncertainty in Kd prediction. As a case study, data from the
      Loire river (France) were considered. The geochemical speciation model takes into
      account complexation of TM with inorganic ligands, sorption of TM with hydrous
      ferric oxides, complexation of TM with dissolved and particulate organic matter
      (i.e. dissolved and particulate humic acids and fulvic acids) and sorption and/or
      co-precipitation of TM to carbonates. Probability Density Functions (PDFs) were
      derived for physico-chemical conditions of the Loire river from a comprehensive
      collection of monitoring data. PDFs for model parameters were derived from
      literature review. Once all the parameters were assigned PDFs that describe
      natural variability and/or knowledge uncertainty, a stepwise structured
      sensitivity analysis (SA) was performed, by starting from computationally
      'inexpensive' Morris method to most costly variance-based EFAST method. The most
      sensitive parameters on Kd predictions were thus ranked and their contribution to
      Kd variance was quantified. Uncertainty analysis was finally performed, allowing
      quantifying Kd ranges that can be expected when considering all the sensitive
      parameters together.

PMID- 30096548
TI  - Insight into mechanism of aged biochar for adsorption of PAEs: Reciprocal effects
      of ageing and coexisting Cd2.
AB  - Biomass derived biochar is a stable carbon-rich product with potential for soil
      amendment. Introduced into the natural environment, biochar will naturally
      experience 'ageing' processes that are liable to change its physicochemical
      properties and the mobility of sorbed pollutants over the longer term. To
      elucidate the reciprocal effects of biochar ageing and heavy metal adsorption on
      the affinity of biochar for organic pollutants, we systematically assessed the
      adsorption of diethyl phthalate (DEP), representative of phthalic acid esters
      (PAEs), to fresh and aged biochars with and without coexistence of Cd2+. Long
      term oxidative ageing was simulated using 5% H2O2 and applied to biochar samples
      made from corn cob, maize straw and wheat straw made by pyrolysis at both 450 
      degrees C and 650  degrees C. Our results showed that biochar made at lower
      temperature (450  degrees C) and from straw exhibited the higher adsorption
      capacity, owing to their greater polarity and abundance of O-containing
      functional groups. The adsorption of DEP onto fresh biochars was found to be
      driven by van der Waals force and H-bonding. Biochar made at the higher
      temperature (650  degrees C) displayed higher carbon stability than that produced
      at lower pyrolysis temperature. Oxidized biochar showed lower adsorption capacity
      than fresh biochar owing to the formation of three-dimensional water clusters on
      biochar surface, which blocked accessible sites and decreased the H-bonding
      effect between DEP and biochars. The coexistence of Cd2+ suppressed the sorption
      of DEP, via competition for the same electron-rich sites. This indicates that
      cation/pi-pi EDA interactions are the primary mechanism for PAE and Cd2+
      stabilization on biochar. Our study sheds light on the mechanism of organic
      pollutant sorption by biochar, as well as the potential susceptibilities of this
      sorption to ageing effects in the natural environment.

PMID- 30096549
TI  - Particulate emission from the gasification and pyrolysis of biomass:
      Concentration, size distributions, respiratory deposition-based control measure
      evaluation.
AB  - Gasification and pyrolysis technologies have been widely employed to produce
      fuels and chemicals from solid wastes. Rare studies have been conducted to
      compare the particulate emissions from gasification and pyrolysis, and relevant
      inhalation exposure assessment is still lacking. In this work, we characterized
      the particles emitted from the gasification and pyrolysis experiments under
      different temperatures (500, 600, and 700  degrees C). The collection
      efficiencies of existing cyclones were compared based on particle respiratory
      deposition. Sensitivity analysis was conducted to identify the most effective
      design parameters. The particles emitted from both gasification and pyrolysis
      process are mainly in the size range 0.25-1.0 MUm and 1.0-2.5 MUm. Particle
      respiratory deposition modelling showed that most particles penetrate deeply into
      the last stage of the respiratory system. At the nasal breathing mode, particles
      with sizes ranging from 0.25 to 1.0 MUm account for around 91%, 74%, 76%, 90%,
      84%, and 79% of the total number of particles that deposit onto the last stage in
      the cases of 500  degrees C gasification, 600  degrees C gasification, 700 
      degrees C gasification, 500  degrees C pyrolysis, 600  degrees C pyrolysis, and
      700  degrees C pyrolysis, respectively. At the oral breathing mode, particles
      with sizes ranging from 0.25 to 1.0 MUm account for around 92%, 77%, 79%, 91%,
      86%, and 81% of the total number of particles that deposit onto the last stage in
      the six cases, respectively. Sensitivity analysis showed that the particle
      removal efficiency was found to be most sensitive to the cyclone vortex finder
      diameter (D0). This work could potentially serve as the basis for proposing
      health protective measures against the particulate pollution from gasification
      and pyrolysis technologies.

PMID- 30096550
TI  - Molecular oxygen loading in candidate theranostic droplets stabilized with
      biocompatible fluorinated surfactants: Particle size effect and application to in
      situ19F MRI mapping of oxygen partial pressure.
AB  - OBJECTIVE: Perfluorocarbon nano- and micron-sized emulsions are a new field of
      investigation in cancer treatment due to their ability to be used as imaging
      contrast agents, or as delivery vectors for pharmaceuticals. They also
      demonstrated capability to enhance the efficiency of high intensity focused
      ultrasound thermo-therapy. In the context of new biomedical applications we
      investigated perfluorooctyl bromide (PFOB) theranostic droplets using 19F NMR.
      Each droplet contains biocompatible fluorinated surfactants composed of a polar
      Tris(hydroxymethyl)aminomethane head unit and hydrophobic perfluorinated tail
      (abbreviated as F-TAC). The influence of the droplet size on the oxygen loading
      capacity was determined from longitudinal relaxation (T1) data of 19F NMR signal.
      MATERIAL AND METHODS: Liquid PFOB and five samples of PFOB droplets of average
      diameter 0.177, 0.259, 1.43, 3.12 and 4.53 um were tested with different oxygen
      levels. A dedicated gas exchange system was validated to maintain steady state
      oxygen concentrations, including a spatial gradient of oxygen concentration. A
      prototyped transmit-receive switchable 19F/1H quadrature coil was integrated on a
      3 T clinical scanner. The coil is compatible with focused ultrasound sonication
      for future application. A spectroscopy FID inversion-recovery (IR) sequence was
      used to measure the T1 value per sample and per value of equilibrium oxygen
      pressure. Pixel wise, spatial T1 mapping was performed with magnetization
      prepared 2D gradient echo sequences in tissue mimicking gels doped with
      theranostic droplets. RESULTS: Experimental data indicated that the longitudinal
      relaxation rate of 19F signal of the investigated theranostic droplets depended
      approximately linearly on the oxygen level and its slope decreased with the
      particle size according to a second order polynomial over the investigated range.
      This semi-empirical model was derived from general thermodynamics and weak
      electrostatic forces theory and fitted the experimental data within 0.75%
      precision. The capacity of oxygen transportation for the described theranostic
      droplets tended to that of pure PFOB, while micron-sized droplets lost up to 50%
      of this capacity. In a specific setup producing a steady state gradient of oxygen
      concentration, we demonstrated spatial mapping of oxygen pressure gradient of 6
      kPa/mm with 1 mm in-plane resolution. CONCLUSION: The size-tunable PFOB
      theranostic droplets stabilized with F-TAC surfactants could be characterized by
      19F MRI in a clinical setup readily compatible with interventional in vivo
      studies under MR guidance. Current precision and spatial resolution of T1 mapping
      are promising. A potential challenge for further in vivo studies is the reduction
      of the imaging time.

PMID- 30096551
TI  - Dynamics of magnetization under stimulus-induced rotary saturation sequence.
AB  - We studied stimulus-induced rotary-saturation preparation (which enables
      measurement of oscillating magnetic fields using MRI) and derived an analytical
      solution of the Bloch equation to understand magnetization dynamics
      mathematically and comprehensively and to conduct simulations without sequential
      calculation techniques such as the Runge-Kutta method. We formulated the dynamics
      using the Bloch equation, introducing an additional rotating frame and some
      approximations to make it into a homogeneous differential equation. Moreover, we
      found that there are two modes depending on the target oscillating magnetic
      field. To confirm the validity of the solution, we experimentally investigated
      its characteristics and performed curve fitting using the analytical model.
      Considering the constraints on the frame, the analytical solution was found to
      agree with experimental data. The experimental data indicate that it is necessary
      to design robust sequences compensating B0 or B1lock spatial inhomogeneity to
      improve measurements. Therefore, experimenters should consider the dynamics of
      magnetization with RF pulses to rewind the spin phase for accurate measurements.

PMID- 30096552
TI  - Acquisition of spatially-resolved displacement propagators using compressed
      sensing APGSTE-RARE MRI.
AB  - A method is presented for accelerating the acquisition of spatially-resolved
      displacement propagators via under-sampling of an Alternating Pulsed Gradient
      Stimulated Echo - Rapid Acquisition with Relaxation Enhancement (APGSTE-RARE)
      data acquisition with compressed sensing image reconstruction. The method was
      demonstrated with respect to the acquisition of 2D spatially-resolved
      displacement propagators of water flowing through a packed bed of hollow
      cylinders. The q,k-space was under-sampled according to variable-density pseudo
      random sampling patterns. The quality of compressed sensing reconstructions of
      spatially-resolved propagators at a range of sampling fractions was assessed
      using the peak signal-to-noise ratio (PSNR) as a quality metric. Propagators of
      good quality (PSNR 33.2 dB) were reconstructed from only 6.25% of all data points
      in q,k-space, resulting in a reduction in the data acquisition time from 4 h to
      14 min. The spatially-resolved propagators were reconstructed using both the
      total variation and nuclear norm sparsifying transforms; use of total variation
      resulted in a slightly higher quality of the reconstructed image in most cases.
      To illustrate the power of this method to characterise heterogeneous flow in
      porous media, the method is applied to the characterisation of flow in a vuggy
      carbonate rock.

PMID- 30096553
TI  - Updating the role of FDG PET/CT for evaluation of lung cancer manifesting in
      nonsolid nodules.
AB  - PURPOSE: To assess the feasibility of using CT to correct specific uptake values
      (SUVs) for fluorodeoxyglucose (FDG) in patients with nonsolid nodules. METHODS:
      Patients with FDG-PET/CT and thin-section CT were included in this pilot study.
      Thirty-five adenocarcinomas manifesting as nonsolid nodules were classified into
      two groups; 90-100% and 1-89% lepidic component. SUVmax was corrected based on
      the CT determination of the proportion of soft tissue component within the cancer
      (SUVatt). RESULTS: Both SUVmax and SUVatt increased as the percentage of the
      lepidic component decreased. SUVmax and SUVatt were significantly different
      between the groups. CONCLUSION: Extent of invasiveness of nonsolid cancers (as a
      marker of aggressiveness) can potentially be quantified by PET/CT using a
      correction method that accounts for the proportion of soft tissue within the
      tumor.

PMID- 30096554
TI  - Endometriosis revisited: an imaging review of the usual and unusual
      manifestations with pathological correlation.
AB  - The manifestations of endometriosis commonly present a diagnostic challenge to
      the gynecologist and radiologist. Familiarity with its varied presentations may
      allow for a more accurate diagnosis. The goal of this review is to the present
      the imaging spectrum of endometriosis, less common sites of involvement as well
      as the potential rare complications. Relevant surgical and histopathological
      correlation is also provided. In addition to clinical evaluation and sonography,
      MRI is a highly accurate imaging modality in the diagnosis of endometriosis. It
      possesses a distinctive advantage over other modalities in that it allows a
      complete survey of the pelvic compartments. The potentially devastating effects
      of endometriosis include pelvic pain and even infertility. Since standard
      treatment is surgical, the radiologist needs to be familiar with the various
      manifestations in order to aid diagnosis for appropriate management.

PMID- 30096555
TI  - Congenital medulloblastoma: Fetal and postnatal longitudinal observation with
      quantitative MRI.
AB  - Congenital medulloblastoma is extremely rare. MRI appearance of this tumor in the
      fetal brain has not been described. A case of congenital medulloblastoma
      initially observed by antenatal MRI with postnatal follow-up and treatment is
      presented. A pregnant female underwent fetal MRI on the 31st gestational week for
      routine indications. Midline cerebellar lesion of <=2 cm in size with minor T2
      hypointensity and T1 hyperintensity was identified. Additionally, quantitative
      MRI including apparent diffusion coefficient (ADC) and fast macromolecular proton
      fraction (MPF) mapping was performed. The lesion showed a marked ADC decrease and
      MPF increase. MPF maps depicted the lesion most conspicuously. After term
      delivery, a male neonate presented with symptoms of increased intracranial
      pressure. Postnatal MRI identified obstructive hydrocephalus caused by a large
      posterior fossa mass. The child was treated by cerebrospinal fluid shunt
      placement. Follow-up quantitative MRI on the fifth month revealed tumor growth
      and vivid changes of its tissue contrast associated with brain maturation. The
      tumor appeared nearly isointense on T1- and T2-weighted images and slightly
      hypointense on the ADC map. MPF contrast showed the most remarkable change from
      hyper- to hypointensity due to brain myelination with stable MPF in the tumor.
      Subsequently, the child underwent partial tumor resection, and currently
      continues treatment with chemotherapy. The pathological diagnosis was
      desmoplastic/nodular medulloblastoma. The described case illustrates evolution of
      the tumor contrast in the course of fetal and postnatal brain development and
      highlights the added diagnostic value of MPF mapping in fetal and neonatal
      neuroimaging.

PMID- 30096556
TI  - MRI of prolapsed polypoid adenomyoma: Expanding the differential diagnosis for
      the broccoli sign.
AB  - We report a 44 year old previously healthy premenopausal woman who presented with
      a three month history of vaginal bleeding and a 5 cm vaginal mass obscuring the
      cervix on physical examination. Ultrasound evaluation was non diagnostic. Pelvic
      MRI demonstrated a 6 cm soft tissue mass in the vagina prolapsed from the uterine
      cavity with a visible connecting stalk, which is termed the broccoli sign. The
      initial radiological differential diagnosis included prolapsed uterine malignancy
      or leiomyoma. Surgical pathology revealed a polypoid adenomyoma. We conclude
      polypoid adenomyoma should be included in the differential diagnosis for
      prolapsed uterine tumor demonstrating the broccoli sign.

PMID- 30096557
TI  - Women in academic musculoskeletal radiology.
AB  - PURPOSE: To determine the proportion of women working in academic musculoskeletal
      (MSK) radiology divisions and how this compares to national benchmarks for women
      in academic medicine. MATERIALS AND METHODS: A list of academic radiology
      departments in the United States was compiled using the U.S. News and World
      Report listing of Best Hospitals for Orthopedics and Rheumatology to aid in
      department selection. Faculty information for MSK radiology divisions was
      obtained using websites pertinent to each department. Figures were obtained from
      the Association of American Medical Colleges and used as a benchmark for
      comparison. RESULTS: The 25 top-ranked hospitals with MSK radiology divisions
      were identified, with a total of 215 MSK trained radiologists. Female
      radiologists made up 33% of the MSK trained faculty (n = 71). This compares to
      38% of fulltime female faculty in academic medicine. 79 assistant professor roles
      were identified, of which 35% were women (n = 28). 34% of associate professors
      were women (n = 11). Only 23% of professors were women (n = 10); this compares
      with 21% of female professors in academic medicine. Six MSK radiologists held
      either chair or vice-chair roles and three of these were women. Of the 24 chief
      or director roles identified, 30% of these were held by women. CONCLUSION: The
      proportions of women within various roles in academic MSK radiology are similar
      to and in some instances higher than corresponding national benchmarks. However,
      there remains a discrepancy between the sexes with an overall male majority.
      Awareness of this fact is the first step required to help correct this imbalance.

PMID- 30096558
TI  - Effects of chelator lipids, paramagnetic metal ions and trehalose on liposomes by
      solid-state NMR.
AB  - The effects of various lipid bound paramagnetic metal ions on liposomes prepared
      in the presence of trehalose and chelator lipids are evaluated to observe site
      specific signal changes on liposome samples with optimal resolution in solid
      state NMR spectroscopy. We found that Mn2+, Gd3+ and Dy3+ have different
      influences on the lipid 13C sites depending on their penetration depths into the
      bilayer, which can be extracted as distance information. The trehalose-liposome
      mixture is efficiently packed into solid-state NMR rotors and provides optimal
      resolution at reasonable instrument temperatures (10-50  degrees C). The
      effectiveness and convenience of the trehalose preparation for studying a
      membrane protein in liposomes are demonstrated by a membrane sample with a model
      membrane peptide to show that trehalose is useful to prepare consistent and
      stable membrane protein liposome samples for solid-state NMR.

PMID- 30096559
TI  - Biomimetic nano-surfactant stabilizes sub-50 nanometer phospholipid particles
      enabling high paclitaxel payload and deep tumor penetration.
AB  - Sub-50 nm nanoparticles feature long circulation and deep tumor penetration.
      However, at high volume fractions needed for intravenous injection, safe, highly
      biocompatible phospholipids cannot form such nanoparticles due to the fluidity of
      phospholipid shells. Here we overcome this challenge using a nano-surfactant, a
      sterilized 18-amino-acid biomimetic of the amphipathic helical motif abundant in
      HDL-apolipoproteins. As it induces a nanoscale phase (glass) transition in the
      phospholipid monolayer, the peptide stabilizes 5-7 nm phospholipid micelles that
      do not fuse at high concentrations but aggregate into stable micellesomes
      exhibiting size-dependent penetration into tumors. In mice bearing human Her-2
      positive breast cancer xenografts, high-payload paclitaxel encapsulated in 25 nm
      (diameter) micellesomes kills more cancer cells than paclitaxel in standard
      clinical formulation, as evidenced by the enhanced apparent diffusion coefficient
      of water determined by in vivo MR imaging. Importantly, the bio-inertness of this
      biomimetic nano-surfactant spares the nanoparticles from being absorbed by liver
      hepatocytes, making them more generally available for drug delivery.

PMID- 30096560
TI  - Dual purpose hafnium oxide nanoparticles offer imaging Streptococcus mutans
      dental biofilm and fight it In vivo via a drug free approach.
AB  - The removal of tenacious dental plaque is of paramount importance; however, early
      diagnosis can be a challenging task in dental clinics due to the limitations of
      current approaches, specifically X-ray-based techniques. We have approached this
      problem by integrating antibacterial properties and X-ray contrast enhancement in
      a single probe specific to colonies of Streptococcus mutans as the most
      predominant and carious oral bacteria. We report the synthesis of an inherently
      therapeutic polymeric silane conjugated hafnium oxide nanoparticles (Hf PS NPs).
      Using a high-affinity pathogen-selective peptide, the concept of molecularly
      targeted X-ray imaging of cariogenic pathogen S. mutans was demonstrated. Ex vivo
      studies using extracted human tooth demonstrated striking X-ray attenuation of
      NPs vs. tooth. Additionally, Hf PS NPs exhibited significant bactericidal
      properties against cariogenic pathogen. Electron microscopy revealed that the
      antibacterial activity occurred via a 'latch and kill' mechanism. Mechanistic
      studies determined that these NPs fragmented bacterial DNA components to exert
      their antimicrobial effect. Importantly, Hf PS NPs effectively inhibited the
      growth of a mature biofilm on an ex vivo human tooth model. Finally, the NPs were
      applied to the rodent model of dental biofilm. Topical administration of the Hf
      PS NPs for 8 days (1X daily) could effectively attenuate the S. mutans biofilm
      challenge. This report is the first of its kind to demonstrate that HfO2-based
      NPs can be used for simultaneous diagnosis and antibacterial treatment without
      requiring an additional drug.

PMID- 30096561
TI  - Activation of human aortic valve interstitial cells by local stiffness involves
      YAP-dependent transcriptional signaling.
AB  - Differentiation of valve interstitial cells (VICs) into pro-calcific cells is one
      of the central events in calcific aortic valve (AoV) disease (CAVD). While the
      paracrine pathways and the responsivity of VICs to mechanical compliance of the
      surrounding environment are well characterized, the molecular programming related
      to variations in local stiffness, and its link to cytoskeleton dynamics, is less
      consolidated. By using a simple method to produce 2D poly-acrylamide gels with
      stiffness controlled with atomic force microscopy (AFM), we manufactured adhesion
      substrates onto which human VICs from stenotic valves were plated, and
      subsequently investigated for cytoskeleton dynamics and activation of the
      mechanosensing-related transcription factor YAP. As a comparison, we employed
      VICs from patients undergoing valve substitution for valve insufficiency, a non
      calcific AoV disease, which does not involve extensive inflammation. While the
      two VICs types did not differ for basic responses onto substrates with different
      stiffness values (e.g. adhesion and proliferation), they were subject to a
      different dynamics of stiffness-dependent YAP nuclear shuttling, revealing for
      the first time an intracellular force transduction mechanism distinctive for
      calcific aortic valve disease. In VICs from stenotic valves, YAP nuclear
      translocation occurred in concert with an increase in cytoskeleton tensioning and
      loading of the myofibroblast-specific protein alphaSMA onto the F-actin
      cytoskeleton. AFM force mapping performed along radial sections of human calcific
      valve leaflets identified, finally, areas with high and low levels of rigidity
      within a similar range to those controlling YAP nuclear translocation in vitro.
      Since VICs juxtaposed to these areas exhibited nuclear localized YAP, we conclude
      that subtle variations in matrix stiffness are involved in mechanosensing
      dependent VICs activation and pathological differentiation in CAVD.

PMID- 30096562
TI  - A systems mechanobiology model to predict cardiac reprogramming outcomes on
      different biomaterials.
AB  - During normal development, the extracellular matrix (ECM) regulates cell fate
      mechanically and biochemically. However, the ECM's influence on lineage
      reprogramming, a process by which a cell's developmental cycle is reversed to
      attain a progenitor-like cell state followed by subsequent differentiation into a
      desired cell phenotype, is unknown. Using a material mimetic of the ECM, here we
      show that ligand identity, ligand density, and substrate modulus modulate
      indirect cardiac reprogramming efficiency, but were not individually correlated
      with phenotypic outcomes in a predictive manner. Alternatively, we developed a
      data-driven model using partial least squares regression to relate short-term
      cell states, defined by quantitative mechanosensitive responses to different
      material environments, with long-term changes in phenotype. This model was
      validated by accurately predicting the reprogramming outcomes on a different
      material platform. Collectively, these findings suggest a means to rapidly screen
      candidate biomaterials that support reprogramming with high efficiency, without
      subjecting cells to the entire reprogramming process.

PMID- 30096563
TI  - Folate-conjugated nanobubbles selectively target and kill cancer cells via
      ultrasound-triggered intracellular explosion.
AB  - With the rapid development of cancer-targeted nanotechnology, a variety of
      nanoparticle-based drug delivery systems have clinically been employed in cancer
      therapy. However, multidrug resistance significantly impacts the therapeutic
      efficacy. Physical non-drug therapy has emerged as a new and promising strategy.
      This study aimed to determine whether novel folate-nanobubbles (F-NBs), combined
      with therapeutic ultrasound (US), could act as a safe and effective physical
      targeted cancer therapy. Using folate-conjugated N-palmitoyl chitosan (F-PLCS),
      we developed novel F-NBs and characterised their physicochemical properties,
      internalization mechanism, targeting ability, therapeutic effects, and killing
      mechanism. The results showed that the novel F-NBs selectively accumulated in FR
      positive endothelial cells and tumour cells via FR coupled with clathrin- and
      caveolin-mediated endocytosis in vitro and in vivo. In addition, the F-NBs killed
      target cells by an intracellular explosion under US irradiation. Hoechst/PI
      staining demonstrated that apoptosis and necrosis accounted for a large
      proportion of cell death in vivo. F-NBs combined with US therapy significantly
      inhibited tumour growth and improved the overall survival of tumour-bearing mice.
      Under US irradiation, the novel F-NBs selectively killed FR-positive tumour cells
      in vitro and in vivo via intracellular explosion and therefore is a promising
      alternative for targeted cancer treatment.

PMID- 30096564
TI  - Corrigendum to 'An innovative Mg/Ti hybrid fixation system developed for fracture
      fixation and healing enhancement at load-bearing skeletal site' [Biomaterials
      (2018) 173-183].

PMID- 30096565
TI  - Photosensitizer-crosslinked in-situ polymerization on catalase for tumor hypoxia
      modulation & enhanced photodynamic therapy.
AB  - Tumor hypoxia is known to be one of critical factors that aggravate the tumor
      resistance to photodynamic therapy (PDT) in which oxygen is essential for tumor
      destruction. Herein, catalase, an enzyme to trigger hydrogen peroxide (H2O2)
      decomposition, is modified by in-situ free radical polymerization, using meso
      tetra(p-hydroxyphenyl) porphine (THPP) as the cross-linker to enable condensed
      grafting of short polyethylene glycol (PEG) chains on the protein surface as a
      permeable brush-like safeguard. The formulated catalase-entrapped nanocapsules
      (CAT-THPP-PEG) with enhanced enzyme stability can be labeled with 99mTc4+, a
      radioisotope ion that is chelated by the porphyrin structure of THPP, to allow in
      vivo single-photon emission computed tomography (SPECT) imaging. It is found that
      such CAT-THPP-PEG nanoparticles exhibit efficient tumor passive retention after
      intravenous injection, and are able to greatly relieve tumor hypoxia by
      triggering the decomposition of tumor endogenous H2O2 into oxygen. With THPP
      functioning as a photosensitizer, in vivo PDT is further conducted, achieving a
      remarkable antitumor therapeutic effect. This work presents an enzyme
      modification strategy by in-situ polymerization with photosensitizer as the cross
      linker to develop multifunctional nano-theranostics with strengthened enzymatic
      stability, efficient tumor passive homing, SPECT imaging capability, enhanced PDT
      efficacy as well as decreased immunogenicity, promising for clinical translation.

PMID- 30096566
TI  - Body balance function of cochlear implant patients with and without sound
      conditions.
AB  - OBJECTIVE: The relation between well-controlled auditory stimulation through
      cochlear implant (CI) and the body balance has been sparsely investigated. The
      purpose of this study was to evaluate the body balance function of CI patients
      with- and without-sound in anechoic sound-shielded room. METHODS: We recorded 8
      experienced CI recipients and 8 young normal-hearing volunteers. All subjects
      were assessed using posturography under 4 conditions: (1) eyes open with-sound,
      (2) eyes closed with-sound, (3) eyes open without-sound, and (4) eyes closed
      without-sound. RESULTS: The total path length and the total area were
      significantly larger in the eyes closed condition than in the eyes open
      condition. In normal hearing subjects, the average displacement of center of
      pressure (COP) in the mediolateral direction under with-sound condition was not
      different from that under without-sound condition. In CI recipients, the COP
      significantly displaced to the CI side after the deprivation of visual cues in
      without-sound condition. This shift was eliminated in with-sound condition
      (significant interaction among sound condition, eye condition, and between-group
      factor). CONCLUSION: In CI subjects, sound stimulation improves the abnormal
      displacement of COP in the mediolateral direction. SIGNIFICANCE: A posturographic
      study under an anechoic condition proved that sound stimulation improves body
      balance function in CI subjects.

PMID- 30096567
TI  - Motor asymmetry over time in Parkinson's disease.
AB  - BACKGROUND: Motor symptoms in Parkinson's disease (PD) patients are usually
      asymmetric at onset. The literature on change in asymmetry over time has mixed
      results, with some studies suggesting a retained asymmetry and others suggesting
      a progression towards symmetry. The aim of this study was to assess change in
      asymmetry over time. METHODS: Charts of 109 consecutive patients who had been
      followed in a movement disorders clinic for routine PD care were retrospectively
      reviewed. All patients had been treated for PD symptoms and had been seen during
      at least 2 annual time points over 5 years. Interval absolute differences in
      Unified PD rating scale (UPDRS) scores for bradykinesia, rigidity, and tremor
      between the right and left sides were calculated for annual time points. RESULTS:
      Neither bradykinesia, rigidity, nor tremor became more symmetric over a 5-year
      period; there was not a statistically significant change in asymmetry at any
      annual time point for these motor symptoms. CONCLUSIONS: The lack of observed
      change in UPDRS score difference suggests that motor symptoms in PD patients
      remain asymmetric. This is important to consider clinically when predicting the
      natural course of PD and considering alternative diagnoses to PD. These results
      may also be important in developing hypotheses for disease progression.

PMID- 30096568
TI  - Consensus recommendations for the diagnosis and treatment of primary progressive
      multiple sclerosis in Latin America.
AB  - : Despite the availability of a large amount of information regarding the
      management and care of relapsing remitting multiple sclerosis (RRMS) patients,
      there is scant information about recommendations on how to care for primary
      progressive MS (PPMS) patients. The objective of this study was to review how
      PPMS patients should be assessed and cared for in Latin America (LATAM). METHODS:
      A panel of neurology experts from LATAM dedicated to the diagnosis and care of MS
      patients gathered virtually during 2017 and 2018 to carry out a consensus
      recommendation on the diagnosis and treatment of PPMS patients in LATAM. To
      achieve consensus, the methodology of "formal consensus-RAND/UCLA method" was
      used. RESULTS: Recommendations focused on disease management, and specific and
      symptomatic disease treatment were determined. The main consensus was that the
      2017 McDonald criteria should be used for diagnosis but that the exclusion of
      regional diseases is strongly recommended; that specific considerations should be
      taken regarding immunotherapy treatments used in MS due to the scarce evidence
      available; and that a general approach that considers symptomatic treatment and
      rehabilitation should be performed in affected patients to improve their status.
      CONCLUSIONS: The recommendations of these consensus guidelines attempt to
      optimize the health care and management of PPMS patients in LATAM.

PMID- 30096569
TI  - Grading of astrocytomas using the PRESTO (principles of echo-shifting with a
      train of observations) magnetic resonance imaging sequence.
AB  - OBJECTIVE: Changes in brain tissue can be detected sensitively using PRESTO
      (principles of echo-shifting with a train of observations) magnetic resonance
      imaging (MRI). The aim of this study was to evaluate the correlation between the
      proliferative ability of astrocytoma and intratumoral spotty signal voids seen as
      hypo-intense dots on PRESTO MRI. PATIENTS AND METHODS: Fifty-seven astrocytic
      tumors, comprising 14 astrocytomas, 12 anaplastic astrocytomas, and 31
      glioblastomas, were included in this retrospective study. The tumors were
      classified independently by blinded radiologists according to the number of
      spotty signal voids detected on PRESTO-MRI as follows: spot-free (grade 0), less
      than 3 spots (grade 1), or more than 3 spots or a large spot (grade 2). RESULTS:
      Thirteen patients (92.9%) with astrocytoma were classified as PRESTO grade 0 and
      1 patient (7.1%) was classified as grade 1. Seven patients (58.3%) with
      anaplastic astrocytoma were classified as PRESTO grade 0, 1 (8.3%) as grade 1,
      and 4 as grade 2 (33.3%). Three patients (9.7%) with glioblastoma were classified
      as grade 0, 6 (19.4%) as grade 1, and 22 (70.9%) as grade 2. There was a strong
      correlation between PRESTO tumor grade and the mean MIB-1 index. CONCLUSIONS:
      These results indicate that a grading system based on the number of spotty signal
      voids detected on PRESTO images would be useful for the diagnosis of astrocytic
      tumors and predicting their proliferative ability.

PMID- 30096570
TI  - Does kyphotic configuration on upright lateral radiograph correlate with
      instability in patients with degenerative lumbar spondylolisthesis?
AB  - OBJECTIVE: To investigate the segmental instability of degenerative lumbar
      spondylolisthesis (DLS) with a kyphotic configuration at the involved segment,
      and to determine the most useful diagnostic modalities in the evaluation of
      instability. PATIENTS AND METHODS: This study reviewed a consecutive series of
      patients with L4/5 DLS between July 2010 and May 2016. The enrolled patients were
      divided into two groups based on preoperative neutral radiographs: the kyphotic
      group (Group K) and non-kyphotic group (Group NK). Translational and angular
      motion was determined by comparing upright lateral radiograph (U) with a supine
      sagittal MR image(S) (Combined, US) or flexion/extension radiographs (FE).
      RESULTS: There were 26 and 201 patients in Groups K and NK, respectively. In
      comparison to Group NK, Group K demonstrated significantly higher translational
      motion (12.4% vs. 7.0%, P < 0.001) on US analysis, but significantly lower
      translational motion (4.2% vs. 6.4%, P < 0.001) on FE analysis. Angular motion
      was detected to be significantly lower in US versus FE in Group NK (1.2 degrees 
      vs. 7.8 degrees , P < 0.001), while of no difference in Group K (P > 0.05). In
      Group K, "instability" was recognized in 84.6% of patients using US versus 11.5%
      patients using FE (P < 0.001); While in Group NK, no significant difference was
      observed in the incidence of "instability" between FE and US (31.3% vs. 27.8%, P
      = 0.444). Overall, Group K had a significantly higher incidence of instability
      than Group NK (84.6% vs. 31.3%, P < 0.001). CONCLUSION: DLS with a kyphotic
      configuration is a distinct subgroup associated with segmental instability. The
      modality of US is shown to be superior to traditional FE in measuring
      translational motion and identifying instability for DLS patients with a kyphotic
      configuration.

PMID- 30096571
TI  - Comparisons of combined oxidant capacity and redox-weighted oxidant capacity in
      their association with increasing levels of FeNO.
AB  - BACKGROUND: Some ozone (O3) and nitrogen dioxides (NO2) health effects studies
      use Ox (sum value) as a surrogate. However, little is known about how this
      related to Oxwt (weighted value). OBJECTIVE: We investigated the effects of redox
      weighted oxidant capacity (Oxwt) on fractional exhaled nitric oxide (FeNO), a
      biomarker of airway inflammation, in a set of chronic obstructive pulmonary
      disease (COPD) patients. We also compare combined oxidant capacity (Ox) and Oxwt
      in their associations with increasing levels of FeNO. METHODS: We measured FeNO
      values in 600 participants who have COPD at Shanghai Pulmonary Hospital. Ox was
      calculated directly by the sum of O3 and NO2. The redox-weighted oxidant capacity
      was calculated by denoting Oxwt as the weighted average of redox potentials. We
      applied generalized additive models (GAM) to investigate the impacts of Ox and
      Oxwt on FeNO levels, respectively. We fitted the same models for the influence of
      O3 and NO2 individually and jointly on FeNO levels to compare the result of Ox
      and Oxwt. RESULTS: Oxwt were significantly linked with FeNO levels. The impact
      was robustest in current day after exposure, and were closely linked with the
      adjustment of PM2.5. A 10 MUg m-3 increase in average Oxwt concentrations was
      linked to 0.88 (95% CI: -1.46, 3.28) increase, whereas a 10 MUg m-3 increase in
      average Ox concentration was linked to 0.62 (95% CI: -0.79, 2.07) increase in
      FeNO. In two-pollutant models, an increase of 10 MUg m-3 in average O3
      concentrations with adjustment of NO2 was associated with 0.57 (95% CI: -1.26,
      2.01) increase in FeNO. The impact estimates of Ox and Oxwt were statistically
      significant among males, non-smoking and elders who age above 65 years old.
      CONCLUSIONS: This analysis demonstrated that Oxwt is used as a better indicator
      of atmospheric oxidative capacity as a proxy of O3 and NO2 in further
      epidemiological studies.

PMID- 30096573
TI  - Aerobic biotransformation of the antibiotic ciprofloxacin by Bradyrhizobium sp.
      isolated from activated sludge.
AB  - Ciprofloxacin (CIP) is an antibiotic that is widely used to treat bacterial
      infections and is poorly biodegraded during wastewater treatment. In this study,
      a CIP-degrading bacterial strain (GLC_01) was successfully retrieved from
      activated sludge by enrichment and isolation. The obtained bacterial strain
      shares over 99% nucleotide identity of the 16S rRNA gene with Bradyrhizobium spp.
      Results show that Bradyrhizobium sp. GLC_01 degraded CIP via cometabolism with
      another carbon substrate following a first-order kinetics degradation reaction.
      CIP degradation by Bradyrhizobium sp. GLC_01 increased when the concentration of
      the primary carbon source increased. The biodegradability of the primary carbon
      source also affected CIP degradation. The use of glucose and sodium acetate (i.e.
      readily biodegradable), respectively, as a primary carbon source enhanced CIP
      biotransformation, compared to starch (i.e. relatively slowly biodegradable). CIP
      degradation decreased with the increase of the initial CIP concentration. Over
      70% CIP biotransformation was achieved at 0.05 mg L-1 whereas CIP degradation
      decreased to 26% at 10 mg L-1. The phylogenetic identification and experimental
      verification of this CIP-degrading bacterium can lead to a bioengineering
      approach to manage antibiotics and possibly other persistent organic contaminants
      during wastewater treatment.

PMID- 30096572
TI  - The metabolism distribution and effect of dinotefuran in Chinese lizards (Eremias
      argus).
AB  - The Chinese lizards (Eremias argus) were used to evaluate the metabolism,
      distribution and effect of dinotefuran following oral exposed. The HPLC equipped
      with Q Exactive focus was used for metabolite identification and concentration
      analysis. After single oral administration, the time-concentration curves of
      dinotefuran and its metabolites were tissue-dependent. The liver and kidney were
      the major metabolic organs. Percutaneous and urinary excretions were the main
      ways for lizards to eliminate dinotefuran, and the urine output was the limiting
      factor. Nitro-reduction was an important process of the metabolism of dinotefuran
      that was dominated by aldehyde oxidase, and P450 enzymes were involved. The
      CYP3A4 and CYP2C19 played a crucial role in the other metabolic pathways of
      dinotefuran. The mRNA expressions of GST family were severely inhibited in liver,
      which showed dinotefuran might pose a risk of damaging the oxidative stress
      system in liver. Prolonged residuals of dinotefuran and its demethylation
      metabolite might enhance the risk of dinotefuran to brain. The results enrich and
      supplement the knowledge of the environmental fate of dinotefuran in reptiles.

PMID- 30096574
TI  - Role of extracellular polymeric substances in efficient chromium(VI) removal by
      algae-based Fe/C nano-composite.
AB  - Subsequent application of the obtained algae by chemical coagulation (e.g.
      Fe(III) addition) presents a challenge because of various iron compounds in
      algae. In this study, algae obtained by chemical coagulation were carbonized to
      yield an algae-based Fe/C nano-composite with a high capacity for hexavalent
      chromium (Cr(VI)) removal (236.9 mg/g), which is attributed to the high reductive
      Fe content (e.g., FeS, Fe(0), and FeO) and specific surface area. The optimal
      conditions-that is, 100 mg/L Fe(III) addition and 800  degrees C-were determined.
      Moreover, the role of extracellular polymeric substances (EPS) in carbonization
      was examined as it affected the product composition and efficiency of Cr(VI)
      removal, owing to the stabilizing property effect of EPS in algae. Algal EPS
      induced the homogeneous distribution of Fe compounds on the surface of the algae,
      and the generated alpha-FeOOH nanoparticles were wrapped in organic carbon
      matrix, resulting in a sufficient reaction between Fe compounds and organic
      carbon during carbonization. X-ray photoelectron spectroscopy showed that
      reduction and adsorption contributed 83.44% and 16.56% to Cr(VI) removal,
      respectively. This study provides a new insight into the role of EPS in the
      efficient Cr(VI) removal by algae-based Fe/C nano-composite and presents a
      promising application of this Fe/C nano-composite in environmental remediation.

PMID- 30096576
TI  - The clinical significance of CDX2 in leukemia: A new perspective for leukemia
      research.
AB  - CDX2 gene encodes a transcription factor involved in primary embryogenesis and
      hematopoietic development; however, the expression of CDX2 in adults is
      restricted to intestine and is not observed in blood tissues. The ectopic
      expression of CDX2 has been frequently observed in acute myeloid and lymphoid
      leukemia which in most cases is concomitant with poor prognosis. Induction of
      CDX2 in mice leads to hematologic complications, showing the leukemogenic origin
      of this gene. CDX2 plays significant role in the most critical pathways as the
      regulator of important transcription factors targeting cell proliferation, multi
      drug resistance and survival. On the whole, the results indicate that CDX2 has
      the potential to be suggested as the diagnostic marker in hematologic
      malignancies. This review discusses the role of aberrant expression of CDX2 in
      the prognosis and the response to treatment in patients with different leukemia
      in clinical reports in the recent decades. The improvement in this regard could
      be of high importance in diagnosis and treatment methods.

PMID- 30096575
TI  - Validation of a HILIC/ESI-MS/MS method for the wood burning marker levoglucosan
      and its isomers in airborne particulate matter.
AB  - In the present study, a methodology involving hydrophilic interaction liquid
      chromatography (HILIC) and electrospray (ESI) tandem mass spectrometry (MS/MS)
      was developed for measurement of anhydrous monosaccharides as markers for wood
      burning in atmospheric aerosols, PM10. No extensive sample preparation, other
      than ultrasound-assisted solvent extraction and evaporation, was applied. A
      pentahydroxysilica column enabled separation of levoglucosan from mannosan and
      galactosan within 5 min and the quantitative performance was validated using the
      standard reference materials (SRM) 1649a and 1649b. The experimentally obtained
      results for SRMs were in agreement with values previously reported in other
      studies. Achieved instrumental limits of detection (LODs) were below 10 pg
      injected on column, corresponding to LODs in air lower than 0.10 ng/m3 for all
      measured isomers for 2-3 day sampling with 1.0 m-3 h-1 sampling rate. The
      validated method was used for the determination of levoglucosan and its isomers
      in atmospheric aerosols collected in three different Swedish urban areas during
      the winter and summer time in 2017. The total measured concentrations for
      levoglucosan and galactosan + mannosan were determined to be between 78 and 167
      ng/m3 in January 2017, which is approximately 10-times higher compared to the
      levels detected in July, reflecting the higher frequency of wood burning for
      heating during the cold season. Calculated concentration ratios between
      levoglucosan and its isomers in the urban area samples indicated mostly mixed
      softwood/hardwood combustion in winter time; on the other hand, softwood burning
      was observed as the major emission in summer time.

PMID- 30096577
TI  - Factors associated with nurses' perceptions, self-confidence, and invitations of
      family presence during resuscitation in the intensive care unit: A cross
      sectional survey.
AB  - BACKGROUND: Family presence during resuscitation is not widely implemented in
      clinical practice. Prior research about nurse factors that may influence their
      decision to invite family members to remain in the room during resuscitation is
      contradictory and inconclusive. OBJECTIVES: To describe intensive care unit
      nurses' perceptions, self-confidence, and invitations of family presence during
      resuscitation, and to evaluate differences according to nurse factors. DESIGN: A
      cross-sectional survey design was used for descriptive and correlational
      analyses. SETTING: Data collection occurred online. PARTICIPANTS: A convenience
      sample of 395 nurses working in intensive care units across the United States was
      obtained. METHODS: Participants completed a survey to collect personal,
      professional, and workplace information. The Family Presence Risk-Benefit Scale
      and Family Presence Self-confidence Scale were administered, and frequency of
      inviting family members to be in the room during resuscitation was collected by
      self-report. Following descriptive analysis of univariate distributions, a series
      of hierarchical OLS regression analyses was used to identify which personal,
      professional, or workplace factors yielded the largest unique impact on nurse
      perceptions, self-confidence, and invitations of family presence during
      resuscitation. RESULTS: Despite high frequency of performing resuscitative care,
      one-third of participants had never invited family members to be in the room
      during resuscitation during their careers, and another 33% had invited family
      members to be present just 1-5 times. Having had clinical experience with family
      presence during resuscitation was the strongest predictor of positive
      perceptions, higher self-confidence, and increased invitations. In addition,
      having received education on family presence during resuscitation and a written
      facility policy were found to be key professional and workplace predictors of
      perceptions and invitations. CONCLUSIONS: Nurses who work in a facility with a
      policy on family presence during resuscitation, are educated on it, and have
      experienced it in the clinical setting are more likely to have positive
      perceptions and higher self-confidence, and to invite family members to be in the
      room during resuscitation with increased frequency. Nurses in leadership roles
      should create policies for their units and provide education to nurses and other
      healthcare providers. Due to the apparent importance of clinical experience with
      family presence during resuscitation, it is recommended to initially provide this
      experience using simulation and role modeling.

PMID- 30096578
TI  - Barriers and facilitators to the provision of preconception care by healthcare
      providers: A systematic review.
AB  - BACKGROUND: Healthcare providers play an important role in providing
      preconception care to women and men of childbearing age. Yet, the provision of
      preconception care by healthcare providers remains low. OBJECTIVES: To provide an
      overview of barriers and facilitators at multiple levels that influence the
      provision of preconception care by healthcare providers. DESIGN: A mixed-methods
      systematic review. DATA SOURCES: PubMed, Web of Science, CINAHL, The Cochrane
      Library, and EMBASE were systematically searched up to April 27, 2017. The search
      strategy contained MeSH terms and key words related to preconception care and
      healthcare providers. Reference lists of included studies and systematic reviews
      on preconception care were screened. REVIEW METHODS: Publications were eligible
      if they reported on barriers and facilitators influencing the provision of
      preconception care by healthcare providers. Data were extracted by two
      independent reviewers using a data extraction form. Barriers and facilitators
      were organized based on the social ecological model. The methodological quality
      of included studies was evaluated using the Critical Appraisal Skills Programme
      Qualitative checklist for qualitative studies, the Quality Assessment Tool for
      quantitative studies, and the Mixed Methods Appraisal Tool for mixed methods
      studies. RESULTS: Thirty-one articles were included. Barriers were more reported
      than facilitators. These were situated at provider level (unfavourable attitude
      and lack of knowledge of preconception care, not working in the field of
      obstetrics and gynaecology, lack of clarity on the responsibility for providing
      preconception care) and client level (not contacting a healthcare provider in the
      preconception stage, negative attitude, and lack of knowledge of preconception
      care). Limited resources (lack of time, tools, guidelines, and reimbursement)
      were frequently reported at the organizational and societal level. CONCLUSIONS:
      Healthcare providers reported more barriers than facilitators to provide
      preconception care, which might explain why the provision of preconception care
      is low. To overcome the different client, provider, organizational, and societal
      barriers, it is necessary to develop and implement multilevel interventions.

PMID- 30096579
TI  - Effects of an education program on toileting behaviors and bladder symptoms in
      overactive bladder patients with type 2 diabetes: A randomized clinical trial.
AB  - BACKGROUND: Overactive bladder is more common in patients with type 2 diabetes
      than in those without diabetes. Many patients with diabetes adopt unhealthy
      toileting behaviors to empty their bladder that may contribute to the onset or
      worsening of overactive bladder. OBJECTIVE: To investigate whether an education
      program targeting toileting behaviors is effective for helping overactive bladder
      patients with type 2 diabetes in terms of adopting healthy toileting behaviors,
      improving bladder symptoms, and enhancing quality of life. DESIGN: The study was
      a parallel, pragmatic, open-label randomized trial. SETTINGS: The trial was
      conducted in a hospital-based endocrinology outpatient department in Jinan,
      China. PARTICIPANTS: A total of 104 patients were randomly assigned to a 6-week
      education program or a control group. METHODS: Primary outcomes included
      toileting behaviors and bladder symptoms, including dry/wet overactive bladder
      and severity of urgency. Secondary outcomes were overactive bladder-specific and
      general quality of life. The patients were reassessed on the outcome variables at
      the end of the intervention and at 3 months and 6 months following the
      intervention. The analysis followed the intent-to-treat principle. To account for
      the longitudinal data with repeated measures, group comparisons for continuous
      outcomes were evaluated using linear mixed models. Group differences in binary
      outcomes were examined using mixed-effects logit models. RESULTS: Compared with
      the control group, the education program group showed significant changes in
      three unhealthy toileting behaviors: premature voiding (-0.7, p < 0.001), place
      preference for voiding (-0.5, p = 0.007), and delayed voiding (-0.2, p = 0.011).
      The program significantly relieved the bladder symptoms (-2.2, p < 0.001) and
      decreased the probability of having wet overactive bladder (-0.3, p < 0.001) and
      the severity of urgency (-0.4, p < 0.001). It also significantly improved the
      overactive bladder-specific quality of life by 10.8 points (p = 0.001). Regarding
      patients' general quality of life, the physical aspect was enhanced by 3.0 points
      (p = 0.049); however, no effect on the mental well-being aspect was observed.
      CONCLUSIONS: Among overactive bladder patients with type 2 diabetes, the 6-week
      education program targeting toileting behaviors resulted in the adoption of
      healthy toileting behaviors, relief of bladder symptoms and improvement in
      quality of life in the 6 months following the intervention compared with routine
      care alone. The education program was highly successful and may represent an
      effective, acceptable, feasible, and safe intervention for improving bladder
      health and quality of life during diabetes care, given that the toileting
      behavioral changes were maintained during the 6-month follow-up period.

PMID- 30096580
TI  - Design, synthesis, antiproliferative activity, molecular docking and cell cycle
      analysis of some novel (morpholinosulfonyl) isatins with potential EGFR
      inhibitory activity.
AB  - New series of 5-(morpholinosulfonyl) isatin derivatives were designed and
      synthesized. The new compounds were characterized on the basis of spectral and
      elemental analyses. They were examined for their cytotoxic effects using SRB
      assay on four cancer cell lines HepG2, HCT116, CACO and MCF-7 in addition to the
      non-cancerous human cell line. They were non cytotoxic towards the normal derived
      cell line (IC50 value > 130 MUM). Compounds 3, 6, 10 and 11 showed IC50 values
      less than 10 MUM on three of the tested cell lines HepG2, HCT116 and CACO.
      Compounds 2h, 5, and 7b showed IC50 values less than or nearly equal 10 MUM on
      HepG2, CACO and HCT116 respectively. Compounds 3 and 6 revelaed IC50 values less
      than 12 MUM on MCF7. These obtained IC50 values are comparable with that of
      doxrubicin as it has showed IC50 range from 4.5 to 8.28 MUM on the tested cell
      lines. All these promising derivatives showed inhibitory activity against EGFR
      with IC50 values less than 2 MUM. The most potent EGFR inhibitors 7b (IC50 = 46
      nM) and 10 (IC50 = 23 nM) showed to cause cell cycle arrest at G2/M phase and
      induce apoptosis. Molecular docking studies also were simulated to put insight
      and make better understanding to their structural features.

PMID- 30096582
TI  - An integrated deep sequencing analysis of microRNAs in transplanted corneas.
AB  - Illumina Hiseq 2500 deep sequencing was used to screen for differentially
      expressed genes (DEGs) in matched pairs of isograft corneas and normal corneas,
      allograft corneas and isograft corneas. Our results showed that 22 miRNAs were
      significantly upregulated and 4 were significantly downregulated in the isograft
      group when compared with the control group (P < 0.01), while 17 miRNAs were
      significantly upregulated and 3 were significantly downregulated in the allograft
      group when compared with the isograft group (P < 0.01). Among the miRNAs with
      altered expression levels, miR-155-5p, miR-142-3p, miR-142-5p, and miR-223-3p
      displayed simultaneous changes in the above two comparisons. Potential target
      genes among the DEGs were predicted using target prediction software (TargetScan,
      Miranda, miRDB, and CLIP), and the overlay portion was analyzed using the Gene
      Ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG). GO
      and KEGG analyses showed that the DEGs were mainly involved in metabolic
      pathways, cytokine secretion, and tumor immunity functions. An analysis of the
      interactions between DEG proteins (PPI analysis) and a MetaCore software analysis
      of 4 key DEGs revealed that the genes regulated by miR-155-5p played important
      roles in the miRNA-mRNA regulatory network. Furthermore, the MetaCore analysis
      identified C/EBP beta, p53, and sp1 as key transcription factors in that network.
      Our study identified transplanted corneas-specific miRNA in matched pairs of
      isograft corneas and normal corneas, allograft corneas and isograft corneas.
      Furthermore, bioinformatics analysis of the key miRNA regulatory network revealed
      the molecular mechanisms, which suggests miRNAs may as new molecular targets for
      treating corneal injuries and corneal transplant rejection.

PMID- 30096581
TI  - Altered formation of the iron oxide nanoparticle-biocorona due to individual
      variability and exercise.
AB  - Nanoparticles (NPs), introduced into a biological environment, accumulate a
      coating of biomolecules or biocorona (BC). Although the BC has toxicological and
      pharmacological consequences, the effects of inter-individual variability and
      exercise on NP-BC formation are unknown. We hypothesized that NPs incubated in
      plasma form distinct BCs between individuals, and exercise causes additional
      intra-individual alterations. 20 nm iron oxide (Fe3O4) NPs were incubated in pre-
      or post-exercise plasma ex vivo, and proteomics was utilized to evaluate BC
      components. Analysis demonstrated distinct BC formation between individuals,
      while exercise was found to enhance NP-BC complexity. Abundance differences of NP
      BC proteins were determined between individuals and resulting from exercise.
      Differential human macrophage response was identified due to NP-BC variability.
      These findings demonstrate that individuals form unique BCs and that exercise
      influences NP-biomolecule interactions. An understanding of NP-biomolecule
      interactions is necessary for elucidation of mechanisms responsible for
      variations in human responses to NP exposures and/or nano-based therapies.

PMID- 30096583
TI  - Interleukin 8 (CXCL8)-CXC chemokine receptor 2 (CXCR2) axis contributes to MiR
      4437-associated recruitment of granulocytes and natural killer cells in ischemic
      stroke.
AB  - Granulocytes and natural killer (NK) cells have been linked to brain injury in
      ischemic stroke. However, their recruitment from peripheral leucocytes in stroke
      patients is not well understood. Here, the expression of the interleukin 8
      (CXCL8) in plasma, and CXC chemokine receptor 2 (CXCR2) in peripheral leucocytes
      of patients with ischemic stroke were evaluated. Based on the results, CXCR2
      expression positively correlated with granulocytes and NK cells, which were in
      turn attracted by CXCL8. The results also indicated that CXCR2 was a direct
      target of microRNA (miR)-4437, a negative regulator of CXCR2, which was
      downregulated in peripheral leucocytes from patients with ischemic stroke.
      Furthermore, serum CXCL8 levels were associated with the infarct volume and
      functional outcomes in patients with ischemic stroke. The results of the receiver
      operating characteristic curve analysis with an optimal cut-off value of 34 pg/mL
      indicated serum CXCL8 levels could be a prognostic indicator for ischemic stroke.
      In conclusion, these data highlighted the involvement of the CXCL8-CXCR2
      chemotactic axis in the recruitment of granulocytes and NK cells in ischemic
      stroke. Furthermore, miR-4437 was suggested as a novel target for treating
      ischemic stroke, while the serum CXCL8 level could be a prognostic factor for
      ischemic stroke.

PMID- 30096588
TI  - In vitro activity of DS-2969b and comparator antimicrobial agents against
      Clostridioides (Clostridium) difficile, methicillin-resistant Staphylococcus
      aureus, and other anaerobic bacteria.
AB  - The in vitro activity of DS-2969b, a novel GyrB inhibitor, and six comparator
      agents was studied against 101 recent North American Clostridioides difficile
      isolates, 46 other intestinal anaerobes and 51 strains of methicillin-resistant
      Staphylococcus aureus. The MIC ranges (MIC90s) of DS-2969b against C. difficile
      and S. aureus were 0.03-0.125 (0.125) MUg/ml and 0.125-1 (0.5) MUg/ml,
      respectively. DS-2969b showed the greatest activity of the agents tested. There
      was no difference in MICs of DS-2969b among different ribotypes.

PMID- 30096586
TI  - Trichoderma harzianum diminished oxidative stress caused by 2,4-
      dichlorophenoxyacetic acid (2,4-D) in wheat, with insights from lipidomics.
AB  - 2,4-dichlorophenoxyacetic acid (2,4-D) is among the most commonly used herbicides
      applied for weed control during wheat cultivation. However, its application could
      affect wheat growth. The present study investigates the effect of the
      ascomycetous fungus Trichoderma harzianum on lipid peroxidation, phospholipids,
      signaling lipids and phospholipase D in the seedlings of wheat (Triticum aestivum
      L.) treated with 2,4-D (2.5 mg L-1). In the group of 4-day-old seedlings exposed
      to the herbicide, increased lipid peroxidation and inhibition of growth were
      observed in shoots and roots. Moreover, elevated levels of oxylipins were noted.
      Among them, the amount of 13-HOTrE oxygenated from linolenic acid (18:3)
      increased the most significantly. Concurrently, in the seedlings inoculated with
      T. harzianum, growth was stimulated when the level of phosphatidylcholine (PC)
      increased. Moreover, in wheat seedlings treated with 2,4-D and T. harzianum, the
      level of lipid peroxidation was similar to that in the control and there was no
      increase observed in oxylipins and phospholipase D activity. T. harzianum might
      have partly alleviated the toxic effect of 2,4-D on wheat seedlings.

PMID- 30096589
TI  - Latent trajectory classes of postpartum depressive symptoms: A regional
      population-based longitudinal study.
AB  - PURPOSE: This study aimed to (a) assess trajectories of women's depressive
      symptoms during the first year postpartum to (b) identify potential unobserved
      classes of women as defined by their trajectories, (c) identify antepartum and
      early postpartum risk factors associated with trajectory classes, and (d) examine
      the association between trajectory classes and counselling during the postpartum
      period. METHODS: Data on depressive symptoms, using the Edinburgh Postnatal
      Depression Scale (EPDS), were collected from 1374 women across nine Norwegian
      well-baby clinics at 1.5, 4, 6, and 12 months postpartum. Well-baby clinics offer
      universal, free services to all families living in the municipality. Thus, there
      were no specific exclusion criteria for this study. All clinics had implemented
      the Edinburgh-method which combines screening for PPD, using the EPDS, with
      supportive counselling. RESULTS: Analyses showed that depressive symptoms
      decreased initially, followed by a flattening in symptoms at 6 months. Mixture
      analyses, however, identified two classes of women with distinct trajectories;
      (1) a low-risk (n = 1249, 91%) and (2) a high-risk group (n = 119, 9%).
      Complications after birth, elevated prenatal depressive symptoms, previous or
      current mental illness, and gestational week, predicted trajectory class
      membership. Women in the high-risk group were more likely to receive counselling
      than low-risk women. LIMITATIONS: Women had higher educational level than the
      general population and one of the municipalities did not have a 12-months routine
      consultation. CONCLUSION: Findings suggest heterogeneity among women in their
      depressive symptoms during the first year postpartum with a distinct set of risk
      factors associated with high-risk women. This has implications for the prevention
      and follow-up of women during pregnancy and the first year after childbirth.

PMID- 30096587
TI  - Assessment of risk factors for cerebrovascular disease among the elderly in
      Beijing: A 23-year community-based prospective study in China.
AB  - INTRODUCTION: There are few studies on how lifestyle factors and mental
      conditions modulate the cerebrovascular diseases (CBVD) mortality risk are rare
      in the Asian elderly. AIM: To comprehensively assess the impact of lifestyle
      factors and mental conditions on the mortality risk of CBVD among the Chinese
      older adults. MATERIAL AND METHODS: This community-based prospective cohort study
      was based on the Beijing Longitudinal Study of Aging. We included 2101
      participants aged >=55 years who were interviewed in August 1992 and followed
      until December 2015. Baseline sociodemographic variables, lifestyle behaviors,
      and medical conditions were collected using a standard questionnaire. In
      addition, biochemical parameters, the Activities of Daily Living (ADL) scale,
      Center for Epidemiological Studies Depression (CES-D) scale, and Mini-Mental
      State Examination (MMSE) were performed. Hazard ratio (HR) and 95% confidence
      intervals (CI) was estimated from the competing risk model. RESULTS: During the
      follow-up period, 576 (27.42%) CBVD events were documented. Multivariable
      analysis showed that hypertension (HR = 2.331, 95% CI = 1.652-3.288,P < 0.001),
      depression (HR=2.331, 95% CI=1.652-3.288, P < 0.001), cognitive impairment
      (HR=1.382, 95% CI=1.132-1.689, P < 0.001), and coronary heart diseases (HR=1.360,
      95% CI=1.095-1.689, P = 0.005) were independently associated with CBVD, while
      body mass index, fasting blood glucose, triglycerides, drinking, and smoking were
      not associated with CBVD (all P > 0.05). CONCLUSIONS: Males were at higher risk
      of CBVD than females. Age, gender, hypertension, cognitive impairment, and
      depression were associated with CBVD among the elderly in Beijing, China.

PMID- 30096590
TI  - Impact of predominant polarity on long-term outcome in bipolar disorder: A 7-year
      longitudinal cohort study.
AB  - INTRODUCTION: Recent studies suggest that Predominant Polarity (PP) may be an
      important specifier of Bipolar Disorder (BD), establishing distinct groups of
      patients and providing a potential tool for tailored treatment. PP has been
      associated to various clinical variables present in the course of the disorder,
      including deficits in cognitive functioning, suicide attempts, hospitalizations
      and response to pharmacological treatment. However, most published studies are
      retrospective and cross-sectional, frequently relying on patients' ability to
      recall past information, which may often be inaccurate. METHODS: Participants
      were recruited from the outpatient clinic of the Bipolar Disorder Research
      Program at the Institute of Psychiatry of the University of Sao Paulo. Baseline
      clinical and demographic variables were collected using a semi-structured
      questionnaire and the SCID-CV. Longitudinal data were collected through medical
      records, mood charts, and mood symptom scales conducted throughout a 7-year
      follow-up period. RESULTS: Manic Predominant Polarity (MPP) was associated with a
      significantly higher number of hospitalizations, suicide attempts, and episodes
      with psychotic symptoms throughout the 7-year observed period in comparison to
      Depressive Predominant Polarity (DPP) and Indefinite Predominant Polarity (IPP)
      patients. Moreover, baseline PP was significantly associated with 7-year PP, with
      67% of patients maintaining their PP both at baseline and after the 7-year follow
      up period. LIMITATIONS: The present study is limited due to the statistically
      small sample size, although, to our knowledge, it is the largest longitudinal
      study conducted in this topic, and the unequally distributed frequency of
      patients' visitations, which may have created intervals of unobserved periods
      within the follow-up period. DISCUSSION: The results revealed PP to be an
      important specifier for predicting the course of the disorder. Overall, MPP was
      significantly associated with variables indicative of a worse outcome, suggesting
      that greater attention to preventive treatment should be addressed to this
      subgroup. Lastly, baseline PP was significantly associated with 7-year observed
      PP, suggesting that patients tend to remain within the same PP throughout the
      course of the disorder.

PMID- 30096591
TI  - Examining components of emotion regulation in relation to sleep problems and
      suicide risk.
AB  - BACKGROUND: Sleep has emerged as an important factor in elevated risk for suicide
      and suicidal behaviors; however, the mechanisms accounting for this relationship
      are poorly understood. Emotion regulation is a well-established correlate of self
      injurious behaviors; however, the broad construct has recently been shown to
      provide limited predictive utility. More nuanced investigations into the
      processes involved in emotion regulation may address this gap. This study sought
      to examine the mediating role of emotion regulation between sleep disturbances
      and suicide risk, as well as to evaluate a moderated mediation model in which
      down- and up-regulation of emotions would moderate this mediation. METHODS:
      Participants were 972 adults recruited from a crowdsourcing website (Amazon's
      Mechanical Turk) who completed self-report questionnaires regarding nightmares,
      suicide risk, and emotion regulation. RESULTS: Emotion regulation mediated the
      direct effect of nightmares on suicide risk and suicide attempts. Downregulation
      of negative affect moderated the mediation of nightmares on suicide risk more
      clearly than upregulation of positive affect, and neither component of emotion
      regulation exhibited moderated mediation in the suicide attempt model.
      LIMITATIONS: Generalizability of our findings from an online community sample
      will need to be established with replication in other samples. Additionally, we
      used cross-sectional measures in our mediation models. CONCLUSIONS:
      Downregulation of negative emotions may be particularly salient in relation to
      the severity of suicide risk and, as a result, relative deficits in this area
      should be considered when making risk determinations.

PMID- 30096592
TI  - Prevalence of postpartum depressive symptoms in a multiethnic population and the
      role of ethnicity and integration.
AB  - BACKGROUND: Postpartum depression (PPD) may have adverse effects on both mother
      and child. The aims were to determine the prevalence of postpartum depressive
      symptoms, PPDS, identify associations with ethnicity and with the level of social
      integration. METHOD: Population-based, prospective cohort study of 643 pregnant
      women (58% ethnic minorities) attending primary antenatal care in Oslo.
      Questionnaires regarding demographics and health issues were collected through
      interviews. PPDS was defined as a sum score >= 10 by the Edinburgh Postnatal
      Depression Scale, used as the main outcome in logistic regression analyses, first
      with ethnicity, second with level of integration as main explanatory factors.
      RESULTS: The prevalence of PPDS was higher in ethnic minorities 12.7% (95% CI:
      9.31-16.09) than in Western Europeans 4.8% (2.26-7.34). Adverse life events, lack
      of social support and depressive symptoms during the index pregnancy were other
      significant risk factors. Western European with PPDS were more likely to have had
      depressive symptoms also during pregnancy than women from ethnic minorities
      (72.2% versus 33.3%, p = 0.041). When replacing ethnicity with integration, a low
      level of integration was independently associated with PPDS (2.1 (1.11-3.95)).
      LIMITATIONS: Cases with PPDS were limited. Heterogeneity in the ethnic groups is
      a concern. CONCLUSION: Both point prevalence and new onset of PPDS was higher
      among ethnic minorities than among Western Europeans. Low level of integration
      was associated with PPDS. Our findings suggest that clinicians should be aware of
      the increased risk of new cases of PPDS among ethnic minorities compared to
      Western European women and offer evidence-based care accordingly.

PMID- 30096593
TI  - Clinical utility of the 15-item geriatric depression scale (GDS-15) for use with
      young and middle-aged adults.
AB  - BACKGROUND: The Geriatric Depression Scale, Short Form (GDS-15) is a widely-used
      depression rating scale for elderly adults. It might be useful for persons across
      the adult lifespan, but more research is needed to support its clinical utility
      with young and middle-aged adults. METHODS: We examined the classification
      accuracy of the GDS-15 in identifying depression cases and non-cases in adults
      aged 18-54 (n = 199) compared to those aged 55-80 (n = 112), using the standard
      cutoff score of 5. Criterion-related validity of the GDS-15 was examined based on
      its chance-corrected agreement with a clinical diagnostic interview. RESULTS:
      Classification accuracy based on receiver operating characteristic (ROC) analysis
      was strong in younger (area under the curve; AUC = 0.92) and older adults (AUC =
      0.94). Sensitivity and specificity of the GDS-15 for identifying depression were
      72% and 97% for younger adults and 86% and 91% for older adults, respectively.
      Classification accuracy did not differ between age cohorts (z = 0.74, p = 0.46).
      Chance-corrected agreement (kappa) between the GDS-15 and the criterion was 71%
      for younger and 74% for older adults. LIMITATIONS: Analyses are based on a
      convenience sample aggregated from three community mental health studies. Minor
      procedural inconsistencies may be present. Group sizes were uneven and
      accentuated cell size differences in the confusion matrices. CONCLUSIONS: The GDS
      15 is brief depression rating scale that shows good diagnostic sensitivity and
      specificity for adults aged 18 and older.

PMID- 30096594
TI  - The risk of glaucoma and serotonergic antidepressants: A systematic review and
      meta-analysis.
AB  - BACKGROUND: The aim of current study was to conduct a systematic review and meta
      analysis to explore the relationship between antidepressant use and glaucoma.
      METHODS: Eight major electronic databases were searched from inception until
      March 19th, 2018 to obtain relevant studies that evaluated associations of
      antidepressants [including selective serotonin reuptake inhibitors (SSRIs) and
      serotonin norepinephrine reuptake inhibitors (SNRIs)] treatment and the risk of
      primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) as
      well as intraocular pressure (IOP), and related anterior chamber parameters
      compared to participants not exposed to antidepressant treatment. A random
      effects meta-analysis was conducted. RESULTS: Six case-control studies and one
      cohort study were eligible (N = 801,754). The use of SSRIs was not associated
      with a higher risk of glaucoma (k = 7, pooled adjusted odds ratio (pAOR) = 0.956,
      95% confidence interval (CI) = 0.807 to 1.133, p = 0.604). In addition, IOP was
      lower in participants exposed to antidepressants (SSRIs and SNRIs) (k = 4,
      Hedges' g = -0.519, 95% CI = -0.743 to -0.296, p < 0.001). Finally, pupillary
      diameter was higher in participants exposed to antidepressant treatment (k = 4,
      Hedges' g = 0.681, 95% CI = 0.462 to 0.900, p < 0.001). LIMITATIONS: High
      heterogeneity of included studies limit the establishment of causal inferences.
      CONCLUSIONS: This meta-analysis indicates that a putative association between the
      use of SSRIs and a higher risk of glaucoma remains to be proven. However,
      antidepressant drug treatment may be associated with significantly lower IOP and
      higher pupillary diameter. The mechanisms underpinning these associations deserve
      further investigation.

PMID- 30096595
TI  - Anisakid and raphidascaridid nematodes (Ascaridoidea) infection in the important
      marine food-fish Lophius litulon (Jordan) (Lophiiformes: Lophiidae).
AB  - The yellow goosefish Lophius litulon is a commercially important marine fish
      species. However, our present knowledge of the occurrence of nematode parasites
      in L. litulon remains incomplete. A total of 42 L. litulon collected from the
      East China Sea were investigated for the presence of ascaridoid nematodes. Eight
      ascaridoid species with different developmental stages were identified using
      morphological and molecular methods, including Anisakis pegreffii (L3s),
      Raphidascaris lophii (L3s), Hysterothylacium fabri (L3s, L4s), H. aduncum (L3s,
      L4s, Ads), H. amoyense (L3s), H. liparis (L3s, L4s), H. zhoushanense (L3s) and H.
      sinense (L4s, Ads). The overall prevalence of infection was 100% (mean intensity
      18.6). Of them, H. fabri (L3s, L4s), H. liparis (L3s, L4s), H. sinense (L4s,
      Ads), H. amoyense (L3s) and H. zhoushanense (L3s) were reported from this fish
      for the first time. Anisakis pegreffii (L3s) with prevalence 83.3% and mean
      intensity 12.1, represents the predominant species. The genus Hysterothylacium
      with six species detected herein, has the highest richness of species diversity.
      Our present results provided important information for determining the
      composition of the nematode parasite fauna of L. litulon in the East China Sea,
      and it is also a key step for the risk assessment of human anisakidosis when L.
      litulon caught from the East China Sea are consumed.

PMID- 30096596
TI  - High prevalence of blaCTX-M-14 among genetically diverse Escherichia coli
      recovered from retail raw chicken meat portions in Japan.
AB  - Global widespread of extended-spectrum beta-lactamase (ESBL)-producing
      Enterobacteriaceae, especially Escherichia coli poses a greater threat in
      healthcare and community settings of humans. Raw meats from food animals
      colonized with ESBL producers may be one of important transmission routes for
      those bacteria in the community. This study investigated the presence of ESBL
      producing E. coli in retail raw chicken and pork meats in Japan. ESBL producers
      were detected from the 59 of 150 (39.3%) chicken samples, but none were from all
      the 50 pork samples tested. The blaCTX-M-14 (17; 24.3%) was most frequently
      identified, followed by blaCTX-M-2 (16; 22.9%), blaSHV-12 (11; 15.7%), and blaCTX
      M-55 (10; 14.3%) among a total of 70 ESBL-producing E. coli isolates from 59
      chicken samples. The isolates with blaCTX-M-14 were often combined with
      phylogroup B1 (9/17) mainly composed of ST162 (7/9), and phylogroup F (5/17) with
      diverse STs. The blaCTX-M-14 was basically associated with the common elements
      ISEcp1 and DeltaIS903 or IS903 in all 17 isolates. In 6 isolates, comprising 5
      phylogroup B1-ST162 and a nontypeable-ST162 isolates, an IS26-truncated ISEcp1
      was identified upstream of the blaCTX-M-14, and a fosA3 was further located
      downstream of DeltaIS903. Furthermore, some mobile genetic elements mediating
      blaCTX-M-14 unique to raw chicken meat portions were identified. The blaCTX-M-2
      gene was preceded by ISEcp1 or ISCR1 in 16 isolates, whereas the presence of
      Deltaorf3 downstream of blaCTX-M-2 was limited only in 6 isolates from Brazilian
      samples though they exhibited diverse phylogroups and STs. The blaCTX-M-55 and
      blaCTX-M-1 shared classical flanking structures, ISEcp1-blaCTX-M-orf477, although
      the length of spacer sequences between ISEcp1 and the start codon of blaCTX-M was
      45 bp and 80 bp for blaCTX-M-55 and blaCTX-M-1, respectively. Among blaSHV-12
      harboring isolates, ST38 was frequently detected (6/11) though their phylogroup
      distribution varied. In conclusion, besides transmission of bla gene-harboring E.
      coli lineages which have adaptability to both human and chicken, spread of mobile
      genetic elements associated with bla genes from E. coli lineages adapted to
      chicken to those adapted to human is highly suggested. Our results provide
      important information to gain a better understanding of the transmission risk of
      bla genes from retail chicken meats to human.

PMID- 30096597
TI  - Comparative haemato-immunotoxic impacts of long-term exposure to tartrazine and
      chlorophyll in rats.
AB  - The haemato-immunotoxic effects of the food colourants tartrazine and chlorophyll
      were evaluated. Thirty adult Sprague Dawley rats were distributed into three
      groups and orally administered water, tartrazine (1.35 mg/kg), or chlorophyll
      (1.35 mg/kg) daily for 90 days. Erythrogram and leukogram profiles were
      evaluated. The lysozyme, nitric oxide, phagocytic activity, and immunoglobulin
      levels were measured. Histological and immunohistochemical evaluations of splenic
      tissues were conducted. Changes in the interleukin (IL) 1beta, 6, and 10 mRNA
      expression levels were assessed. In the tartrazine-treated rats, a significant
      anaemic condition and marked leukocytosis were observed. Both the innate and
      humoural parameters were significantly depressed. Different pathological lesions
      were observed, including red pulp haemorrhages, vacuolation of some splenic
      cells, focal hyperplasia of the white pulp, and capsular and parenchymal
      fibrosis. A marked increase in vascular endothelial growth factor (VEGF) and
      endothelial nitric oxide synthase (e-NOS) immunolabelling was evident. Marked
      upregulation of IL-1beta, IL-6, and IL-10 was recorded. In contrast, the
      chlorophyll-treated rats showed minimal haemato-immune responses. These results
      indicate that tartrazine exerts haematotoxic and immunotoxic effects following
      long-term exposure, whereas chlorophyll is a less hazardous food colourant.

PMID- 30096598
TI  - Shikimic acid prevents cartilage matrix destruction in human chondrocytes.
AB  - Abnormal reduction of extracellular matrix (ECM), including type II collagen and
      aggrecan, caused by tumor necrosis factor-alpha (TNF-alpha) is an important
      pathological feature of osteoarthritis (OA). Shikimic acid (SA), derived from
      natural plants, has displayed effective pharmacological properties in diverse
      diseases. The biological roles of SA in OA have not been reported before. Here,
      we found that treatment with SA (1 mM, 10 mM) prevented TNF-alpha-induced
      degradation of type II collagen and aggrecan ECM in human primary chondrocytes
      culture in vitro. Importantly, we also reported that SA treatment reduced TNF
      alpha-induced expression of matrix metalloproteinase-1, -3, and -13 (MMP-1, -3,
      and -13) and increased expression of tissue inhibitor of metalloproteinase-1 and 
      2 (TIMP-1, -2). Additionally, SA treatment attenuated TNF-alpha-induced
      expression of a disintegrin and metalloprotease-4 and -5 (ADAMTS-4, -5).
      Mechanistically, we found that SA prevented activation of the nuclear factor
      kappaB (NF-kappaB) pathway. Our findings suggest that SA might act as an
      important therapeutic agent in the treatment of OA.

PMID- 30096599
TI  - Interaction of mannose binding lectin and other pattern recognition receptors in
      human corneal epithelial cells during Aspergillus fumigatus infection.
AB  - Mannose binding lectin (MBL), a member of C-type lectin superfamily, plays a
      significant role in the innate immune system as one of the Pattern-Recognition
      Receptors (PRRs). This study investigated the relationship between MBL and other
      PRRs including Dectin-1and TLR2, and detected the reaction of MBL towards the
      expression of cytokines in human corneal epithelial cells (HCECs) and murine
      corneas upon Aspergillus fumigatus (A. fumigatus) hyphae infection. We found that
      MBL was significantly up-regulated in C57BL/6 corneas infected with A. fumigatus
      and HCECs incubated with A. fumigatus hyphae. Moreover, both of mRNA and protein
      levels of Dectin-1, TLR2, IL-1beta and TNF-alpha were increased dramatically to
      peak point with the pretreatment of exogenous MBL, while decreased significantly
      with the pretreatment of MBL monoclonal antibody in HCECs. Pretreatment with
      laminarin and TLR2 neutralizing antibody decreased both of mRNA and protein
      levels of MBL and proinflammatory mediators (IL-1beta and TNF-alpha) in A.
      fumigatus hyphae infected HCECs. These data demonstrate that A. fumigatus
      introduce the expression of MBL in human corneas, C57BL/6 corneas and HCECs. MBL,
      Dectin-1 and TLR2 interact with each other upon the treatment of A. fumigatus,
      and MBL contributes to the innate immune responses by regulating proinflammatory
      mediators, such as IL-1beta and TNF-alpha.

PMID- 30096600
TI  - Allergenicity assessment of Buchanania lanzan protein extract in Balb/c mice.
AB  - Tree nuts are among "Big Eight" and have been reported globally for causing
      allergy. Buchanania lanzan (Bl) is one of the major tree nuts consumed by Indian
      population. However, very little is known about B. lanzan's induced allergic
      manifestation. Therefore, evaluation of it's allergenic potential was undertaken.
      Bl-crude protein extract sensitized BALB/c mice sera were used to identify the
      allergic proteins by it's IgE binding capability. The major IgE binding proteins
      found with molecular weight of 11, 20, 23, 25, 48, 54, and 65 kDa. Specific IgE,
      specific IgG1, MCPT-1, PGD2 and histamine were assessed in mice sera. Enormous
      amount of mast cell infiltration was noted in different organs. The levels of
      Th1/Th2 transcription factors GATA-3, SOCS3 and STAT-6 were found upregulated,
      whereas T-bet was downregulated. Furthermore, elevated Th1/Th2 cytokine responses
      were observed in mice sera. All together, these reactions developed systemic
      anaphylaxis upon Bl-CPE challenge in sensitized BALB/c mice. In order to confirm
      the evidences obtained from the studies carried out in BALB/c, the investigation
      was extended to human subjects as well. Control subjects and allergic patients
      were subjected to skin prick test (SPT). Later sera collected from those positive
      to SPT along with controls were used for IgE immunoblotting. The study evaluated
      the allergic manifestation associated with Bl, and identified it's proteins
      attributing Bl-mediated allergy. This work may help in managing tree nuts
      mediated allergies especially due to Buchanania lanzan sensitization.

PMID- 30096601
TI  - Nitric oxide alleviates toxicity of hexavalent chromium on tall fescue and
      improves performance of photosystem II.
AB  - Tall fescue (Festuca arundinacea Schreb) was widely studied for phytoremediation
      of organic or heavy metal contaminated soils. However, there is still little
      information concerning toxicity of chromium (Cr) to tall fescue and roles of
      nitric oxide (NO) in plants against Cr(VI) stress. In this study, different
      Cr(VI) treatments (0, 1, 5 and 10 mg/L Cr(VI)) and NO treatments were applied
      with different combinations in hydroponics culture and their interactions to tall
      fescue were studied. Specifically, 100 uM sodium nitroprusside (SNP) and 100 uM
      NG-nitro-L-arginine-methyl ester (L-NAME) treatments were used to apply exogenous
      NO or inhibit synthesis of NO respectively. Our results showed that tall fescue
      exhibits comparable Cr(VI) tolerance as wheat (Triticum aestivum L.).
      Additionally, Cr(VI) accumulation in tall fescue leaves were carefully studied
      and discussed. Moreover, we observed the significantly increased reactive oxygen
      species (ROS) contents of tall fescue when subjected to Cr(VI) stress, as well as
      decreased photosynthetic activities induced by Cr(VI) stress by methods of
      chlorophyll a fluorescence transient, slow chlorophyll fluorescence kinetics and
      rapid light response curves. Decreased behaviors of photosynthetic activities may
      due to destruction of antennae pigments by Cr(VI), ROS burst induced by Cr(VI),
      and down regulation of photosystem II (PSII) by non-photochemical quenching to
      avoid over reduction of quinone A, which could be considered as an important
      strategy to cope with Cr(VI) stress. Meanwhile, exogenous NO treatment improves
      overall physiological and photosynthetic behaviors of tall fescue against Cr(VI)
      stress. Moreover, increased translocation factors and improved Cr(VI) tolerance
      of plants under exogenous NO treatment suggest that SNP treatment could be a
      useful application for Cr phytoremediation.

PMID- 30096602
TI  - Regenerative potential of bone marrow mesenchymal stem cells on cadmium chloride
      induced hepato-renal injury and testicular dysfunction in sprague dawley rats.
AB  - The effect of bone marrow-derived mesenchymal stem cells on cadmium-induced liver
      and kidney damage was studied in Sprague Dawley rats. The study employed three
      animal groups: Group 1 served as control animals; Group 2 rats were dosed intra
      peritoneally with 2 mg of cadmium chloride per kg body weight, and Group 3 rats
      were again dosed with a single intraperitoneal injection of 2 mg of cadmium
      chloride per kg body weight two doses of 106 cells each intravenously. Finally,
      the animals were killed using halothane inhalation anesthesia. Semen analysis
      (total sperm count, viability, motility, and % of normal sperm), biochemical
      estimations (serum total protein, uric acid, creatinine, levels of enzymes ALT,
      AST, and ALP, and levels of hormones LH, FSH, Inhibin, and testosterone), and
      histopathological analysis of liver and kidney tissue sections (using
      hematoxylene and eosin stains) were conducted. The results showed that when
      compared to controls, cadmium exposure drastically decreased total sperm count,
      viability, motility, and % of normal sperm, decreased serum total protein,
      increased serum uric acid and creatinine levels, increased levels of ALT, AST,
      and ALP enzymes, decreased levels of testosterone and inhibin, increased levels
      of LH and FSH, and caused significant histopathological abnormalities in both
      kidney and liver tissues. Treatment with stem cells ameliorated the effects of
      cadmium-induced toxicity significantly (p < 0.05) of the histopathological and
      biochemical parameters. In conclusion, the study reinforces previous findings
      that bone marrow mesenchymal stem cells can ameliorate the toxic effects of
      cadmium chloride and may be used as a potential therapeutic strategy for cadmium
      induced adverse effects.

PMID- 30096603
TI  - Inoculated Clitoria ternatea with Bacillus cereus ERBP for enhancing gaseous
      ethylbenzene phytoremediation: Plant metabolites and expression of ethylbenzene
      degradation genes.
AB  - Air pollutants especially polyaromatic hydrocarbons pose countless threats to the
      environment. This issue demands for an effective phytoremediation technology. In
      this study we report the beneficial interactions of Clitoria ternatea and its
      plant growth promoting endophytic bacteria Bacillus cereus ERBP by inoculating it
      for the remediation of 5 ppm airborne ethylbenzene (EB). The percentage
      efficiency for ethylbenzene removal among B. cereus ERBP inoculated and non
      inoculated sterile and natural C. ternatea has also been determined. The
      inoculation of B. cereus ERBP has significantly increased EB removal efficiency
      of both sterile and natural C. ternatea. The inoculated natural C. ternatea
      seedlings showed 100% removal efficiency within 84 h for the aforementioned
      pollutant compared with the sterile inoculated C. ternatea seedlings (108 h). The
      degradation of EB by C. ternatea seedlings with and without B. cereus ERBP was
      assessed by measuring the intermediates of EB including 1-phenylethanol,
      acetophenon, benzaldehyde and benzoic acid. In addition, cytochrome P450s
      monooxygenase (CYP83D1) and dehydrogenases (LOC100783159) involved in the
      oxidation of hydrocarbons are well reported for their bio catalytic activities
      under xenobiotic stress conditions. Hence, the co-effect of the native endophyte
      B. cereus ERBP inoculation and EB exposure on the expression level of CYP83D1 and
      dehydrogenase were also determined. The targeted genes CYP83D1and dehydrogenases
      have shown an increased expression level under the 5 ppm of EB exposure enabling
      C. ternatea to withstand and remediate the pollutant.

PMID- 30096604
TI  - Update on thirdhand smoke: A comprehensive systematic review.
AB  - OBJECTIVE: The objective of this study is to perform a comprehensive review of
      the literature about thirdhand smoke (THS). METHODS: Systematic review of all
      aspects of THS. Standard methodological procedures were used to search the
      following databases through April 2018: MEDLINE, Cumulative Index to Nursing and
      Allied Health Literature (CINAHL), Cochrane Central Register of Controlled Trials
      (CENTRAL), and Web of Science (WOS) in Indo-European languages. To identify
      published grey literature, the first 200 hits from Google ScholarTM were
      evaluated. Clinical trial databases, conference proceedings, and reference lists
      from the identified articles were also searched. Two unblinded review authors
      independently assessed trials for inclusion in the review. These same reviewers
      also extracted study data in accordance with PRISMA guidelines. The study
      protocol was registered with PROSPERO (CRD42018083619). RESULTS: Sixty-eight
      articles were included in this systematic review. Of these, 28 analyzed the
      concentration of nicotine as a component of THS (the most commonly-used method to
      measure THS in those studies was chromatography, followed by the mass
      spectrometry), 21 evaluated the exposure and impact of THS on health (11 studies
      analyzed the effect of THS in cells [human and animal], 4 in animals, 1 in
      adults, and 5 in children), 16 investigated the beliefs, behaviours, and policies
      related to THS, and 3 evaluated other aspects such as THS in e-cigarettes or
      hookahs. In these 68 studies, THS was determined by measuring the following
      components: nicotine (30 studies), nitrosamines (17 studies) and cotinine (15
      studies). The findings from most of these studies suggest a potential health
      impact of THS exposure (i.e.: cytotoxicity, metabolic alterations in metabolism,
      in glycemia; or cell structure; alterations in liver, lung, skin and behaviour in
      mice), and low awareness about the risks of THS among the general population.
      CONCLUSIONS: Numerous specific biomarkers of THS were evaluated, with the most
      common being nicotine, nitrosamines, and cotinine. The most common method of
      preparing THS dust samples were cotton wipes, while chromatography, used alone or
      coupled with mass spectrometry, was the most common analytical technique. We have
      tried to establish common bases after reviewing all the current literature of the
      THS although, there is great heterogeneity between the studies and we have not
      always succeeded. The studies in this review demonstrate the harmful effects of
      THS on health in cells, in animal models, and in people including children.
      However, in people, the long-term effects remain unknown and more research is
      needed. These studies show that knowledge about THS and its potential harmful
      effects are poorly understood among the general population. For this reason, THS
      should receive greater emphasis in education and awareness policies.

PMID- 30096605
TI  - Examining the role of sub-foundation soil texture in chlorinated vapor intrusion
      from groundwater sources with a two-layer numerical model.
AB  - In this study we investigate the role of the sub-foundation soil texture in
      determining groundwater source-to-indoor air attenuation factors. A three
      dimensional numerical model was used to simulate a series of two-layer scenarios,
      involving different sub-foundation and deep soil textures, foundation types and
      groundwater source depths. The results indicate that if the sub-foundation soil
      permeability is larger than 10-11 m2, the convection dominates the soil gas
      transport into the building, and the indoor air concentration increases by half
      an order of magnitude with one order of magnitude increase of the sub-foundation
      soil permeability. Otherwise, diffusion plays a more important role and the sub
      foundation soil texture does not cause significant variation of indoor air
      concentration. We found that, independently from the deep soil texture, the
      capillary fringe offers the main resistance to vapor transport. In these cases,
      the deep soil texture could induce at most half an order of magnitude of
      variation in total effective diffusion coefficient in deep soil as well as
      groundwater source-to-indoor air attenuation factors. Finally, we found that, as
      the thin capillary zone represents the higher resistance to upward soil gas flow,
      groundwater source depth has little influence in determining the chlorinated
      vapor intrusion risk.

PMID- 30096606
TI  - Ultrasonic-assisted dispersive micro solid-phase extraction based on melamine
      phytate supermolecular aggregate as a novel bio-inspired magnetic sorbent for
      preconcentration of anticancer drugs in biological samples prior to HPLC-UV
      analysis.
AB  - In this work, a new bio-inspired magnetic sorbent doped melamine-phytate
      supermolecular aggregate (Fe3O4/MPA) was applied in ultrasonic assisted
      dispersive micro solid-phase extraction (Fe3O4/MPA-UA-DMSPE) for the extraction
      of trace quantities of tyrosine kinase inhibitors (TKIs) (dasatinib, erlotinib,
      nilotinib). For this purpose, a mixture of phytic acid and melamine formed a
      supramolecular aggregate. In fact, adhesion between the carbon frameworks and
      nanoparticles was achieved by phytic acid as a crosslinker in order to prevent
      pores from collapsing. Then, Fe3O4 magnetic nanoparticles were doped into the
      aggregate pores and used as a magnetic sorbent. Ultrasonication was performed to
      enhance the dispersion of the sorbent with high extraction recovery. The magnetic
      property of the sorbent, helped with the quick separation of drugs from
      biological samples after their interaction with the sorbent surface. Methanol
      containing imidazole, as an effective eluent was used for desorption of the TKIs
      from the sorbent prior to their quantification by HPLC-UV detection. The chemical
      characteristics of the prepared Fe3O4/MPA were studied by FT-IR (Fourier
      Transform-Infrared Spectroscopy) and XRD (X-ray diffraction) analytical
      techniques. Also, BET (Brunauer-Emmett-Teller) and BJH (Barrett-Joyner-Halenda)
      were used for calculating the specific surface area and pore characteristics.
      Under assessed conditions, the limits of detection (LODs) and the limits of
      quantitation (LOQs) were obtained in the range of 0.12-0.2 and 0.3-0.6 MUg L-1
      respectively. The intra-day and inter-day precisions (RSDs, n = 6) were lower
      than 5 and 7% respectively. Finally, the method was successfully applied for the
      determination of three anticancer drugs (TKIs) in human plasma, serum and urine
      samples with good recoveries.

PMID- 30096607
TI  - Simultaneous determination of the novel anti-tumor candidate drug MDH-7 and 5
      fluorouracil in rat plasma by LC-MS/MS: Application to pharmacokinetic
      interactions.
AB  - MDH-7 (2,3,9-tri-O-acetyl-5,6-dideoxy-1,10-di-[N4'-pentoxycarbonyl-5'-fluoro
      cytosine]-4-ulose 1,4: 7,10-difuranose-4,8-pyranose) is a novel anti-tumor drug
      candidate. To study the pharmacokinetic interaction between MDH-7 and 5
      fluorouracil (5-FU), a sensitive and rapid liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method was developed to simultaneously determine the
      concentrations of MDH-7 and 5-fluorouracil (5-FU) in rat plasma. Plasma samples
      were prepared by simple liquid-liquid extraction with ethyl acetate.
      Chromatographic separation was performed on a Waters XBridgeTM C18 column (5 MUm,
      2.1 mm * 150 mm) with the mobile phase of methanol and H2O (80:20, v/v). The ESI
      positive and negative ion switch was operated in the multiple reactions
      monitoring (MRM) mode. The calibration curves showed good linearity (r2 > 0.99)
      over the ranges of 50-8000 ng/mL for MDH-7 and 10-2000 ng/mL for 5-FU,
      respectively. The lower limit of quantitations (LLOQs) was 50 ng/mL (MDH-7) and
      10 ng/mL (5-FU) with relative standard deviation (RSD) < 13.0%. The proposed
      method was successfully applied to simultaneous assessment of pharmacokinetic
      drug-drug interaction between MDH-7 and 5-FU in rats.

PMID- 30096608
TI  - Activated charcoal significantly improved the reliability of methods for
      quantitative analysis of endogenous substances in biological specimens:
      Glutathione and cysteine as cases.
AB  - When developing a quantitative assay for exogenous or endogenous compounds,
      guidelines for method validation normally recommend that the biological specimens
      should be prepared in corresponding authentic matrices, yet "analyte-free
      authentic matrices" is in general not available. It is generally known that GSH
      and CYS are endogenous compounds and present in both prokaryotes and eukaryotes.
      Herein, an efficient approach for the quantitative analysis of endogenous
      substances in biological specimens was developed, and glutathione (GSH) &
      cysteine (CYS) were chosen as model endogenous substances. Activated carbon (AC),
      a common adsorbent for the adsorption of environmental pollutants, was used to
      remove the endogenous GSH and CYS and prepare "GSH&CYS-free biological matrix".
      The endogenous GSH and CYS in mouse plasma, blood and liver homogenate were found
      can be almost removed via incubating with 100 mg of AC for 2 h. After optimizing
      the derivatization reagents, internal standard and analytical parameters, a
      reliable quantitative assay of GSH and CYS in mouse plasma, blood and liver
      homogenate was developed and validated on LC-ESI-MS/MS using corresponding AC
      adsorbed mouse biological matrices. The validation results indicated that the
      developed method provided suitable accuracy, sensitivity, specificity and high
      throughput for the analysis of GSH and CYS. Finally, the developed LC-ESI-MS/MS
      assay was successfully applied to measure the concentrations of GSH and CYS in
      liver injury mice. The presently developed methodology could be widely applied in
      the quantitative analysis of endogenous compounds in various complex mixtures
      such as biological, herbal and environmental samples.

PMID- 30096609
TI  - Maternal cell phone use during pregnancy and child cognition at age 5 years in 3
      birth cohorts.
AB  - BACKGROUND: There have been few studies of children's cognitive development in
      relation to mothers' cell phone use, and most were limited to outcomes at age 3
      years or younger. We examined the relationship between maternal cell phone use
      during pregnancy and cognitive performance in 5-year old children. METHODS: This
      study included data from 3 birth cohorts: the Danish National Birth Cohort (DNBC)
      (n = 1209), Spanish Environment and Childhood Project (INMA) (n = 1383), and
      Korean Mothers and Children's Environment Health Study (MOCEH) (n = 497). All
      cohorts collected information about maternal cell phone use during pregnancy and
      cognitive performance in children at age 5. We performed linear regression to
      compute mean differences (MD) and 95% confidence intervals (CI) in children's
      general, verbal, and non-verbal cognition scores comparing frequency of maternal
      prenatal cell phone use with adjustments for numerous potential confounding
      factors. Models were computed separately for each cohort and using pooled data in
      meta-analysis. RESULTS: No associations were detected between frequency of
      prenatal cell phone use and children's cognition scores. Scores tended to be
      lower in the highest frequency of use category; MD (95% CI) in general cognition
      scores were 0.78 (-0.76, 2.33) for none, 0.11 (-0.81, 1.03) for medium, and -0.41
      (-1.54, 0.73) for high compared to low frequency of use. This pattern was seen
      across all cognitive dimensions, but the results were imprecise overall.
      CONCLUSION: We observed patterns of lower mean cognition scores among children in
      relation to high frequency maternal prenatal cell phone use. The causal nature
      and mechanism of this relationship remain unknown.

PMID- 30096611
TI  - Population histamine burden assessed using wastewater-based epidemiology: The
      association of 1,4-methylimidazole acetic acid and fexofenadine.
AB  - Systematic sampling and analysis of wastewater has become an important tool for
      monitoring consumption of drugs and other substances, and has been proposed as a
      method to evaluate aspects of population health using endogenous biomarkers. 1,4
      methylimidazoleacetic acid (MIAA) is an endogenous biomarker and metabolite of
      histamine turnover. Its urinary excretion is elevated in conditions such as
      mastocytosis, hay fever, hives, food allergies and anaphylaxis. The aim of this
      study was to develop and apply methods for MIAA in wastewater and compare its
      occurrence with antihistamine use in wastewater. Consecutive daily samples were
      collected from seven catchments serving populations from 3000 to 2 million and
      covering rural and urban communities during the 2016 Census in Australia. MIAA
      and the antihistamines (ranitidine, fexofenadine, cetirizine) were quantified
      consistently. Per capita excretion of MIAA (mg/d/capita) estimated from the WW
      concentrations were consistent with findings from previous clinical studies. We
      found significant positive correlations between loads of MIAA and fexofenadine
      (R2 = 0.68, p < 0.0001) and cetirizine (R2 = 0.25, p = 0.03) across the various
      catchments. Sewer reactor experiments on the degradation of MIAA and the
      antihistamines found that fexofenadine is stable for at least 24 h while MIAA,
      ranitidine and cetirizine are subject to degradation, and this should be
      considered in interpretations. To the best of our knowledge, this study is the
      first wastewater study to introduce and monitor an endogenous metabolite of
      histamine, and the first study to monitor and relate proxies of disease and
      treatment of disease.

PMID- 30096612
TI  - Associations between maternal residential proximity to air emissions from
      industrial facilities and low birth weight in Texas, USA.
AB  - BACKGROUND: Most previous studies examining associations between maternal
      exposures to air pollutants during pregnancy and low birth weight (LBW) in
      offspring focused on criteria air pollutants (PM2.5, PM10, O3, NO2, SO2, CO, and
      Pb). The relationship between non-criteria air pollutants and LBW is understudied
      and requires greater coverage. OBJECTIVES: This study investigated associations
      between maternal residential exposure to industrial air pollutants during
      pregnancy and LBW in offspring. METHODS: This study used a case-control study
      design that included 94,106 term LBW cases and 376,424 controls. It covered 78
      air pollutants common to both the Toxics Release Inventory (TRI) and ground air
      quality monitoring databases in Texas during 1996-2008. A modified version of the
      Emission Weighted Proximity Model (EWPM), calibrated with ground monitoring data,
      was used to estimate maternal residential exposure to industrial air pollutants
      during pregnancy. Binary logistic regression analyses were performed to calculate
      odds ratios (ORs) reflecting the associations of maternal exposure to industrial
      air pollutants and LBW in offspring, adjusted for child's sex, gestational weeks,
      maternal age, education, race/ethnicity, marital status, prenatal care, tobacco
      use during pregnancy, public health region of maternal residence, and year of
      birth. In addition, the Bonferroni correction for multiple comparisons was
      applied to the results of logistic regression analysis. RESULTS: Relative to the
      non-exposed reference group, maternal residential exposure to benzene (adjusted
      odds ratio (aOR) 1.06, 95% confidence interval (CI) 1.04, 1.08),
      benzo(g,h,i)perylene (aOR 1.04, 95% CI 1.02, 1.07), cumene (aOR 1.05, 95% CI
      1.03, 1.07), cyclohexane (aOR 1.04, 95% CI 1.02, 1.07), dichloromethane (aOR
      1.04, 95% CI 1.03, 1.07), ethylbenzene (aOR 1.05, 95% CI 1.03, 1.06), ethylene
      (aOR 1.06, 95% CI 1.03, 1.09), mercury (aOR 1.04, 95% CI 1.02, 1.07), naphthalene
      (aOR 1.03, 95% CI 1.01, 1.05), n-hexane (aOR 1.06, 95% CI 1.04, 1.08), propylene
      (aOR 1.06, 95% CI 1.03, 1.10), styrene (aOR 1.06, 95% CI 1.04, 1.08), toluene
      (aOR 1.05, 95% CI 1.03, 1.07), and zinc (fume or dust) (aOR 1.10, 95% CI 1.06,
      1.13) was found to have significantly higher odds of LBW in offspring. When the
      estimated exposures were categorized into four different groups (zero, low,
      medium, and high) in the analysis, eleven of the fourteen air pollutants, with
      the exception of benzo(g,h,i)perylene, ethylene, and propylene, remained as
      significant risk factors. CONCLUSIONS: Results indicate that maternal residential
      proximity to industrial facilities emitting any of the fourteen pollutants
      identified by this study during pregnancy may be associated with LBW in
      offspring. With the exception of benzene, ethylbenzene, toluene, and zinc, the
      rest of the fourteen air pollutants are identified as LBW risk factors for the
      first time by this study. Further epidemiological, biological, and toxicological
      studies are suggested to verify the findings from this study.

PMID- 30096610
TI  - Particulate matter air pollution components and incidence of cancers of the
      stomach and the upper aerodigestive tract in the European Study of Cohorts of Air
      Pollution Effects (ESCAPE).
AB  - INTRODUCTION: Previous analysis from the large European multicentre ESCAPE study
      showed an association of ambient particulate matter <2.5 MUm (PM2.5) air
      pollution exposure at residence with the incidence of gastric cancer. It is
      unclear which components of PM are most relevant for gastric and also upper
      aerodigestive tract (UADT) cancer and some of them may not be strongly correlated
      with PM mass. We evaluated the association between long-term exposure to
      elemental components of PM2.5 and PM10 and gastric and UADT cancer incidence in
      European adults. METHODS: Baseline addresses of individuals were geocoded and
      exposure was assessed by land-use regression models for copper (Cu), iron (Fe)
      and zinc (Zn) representing non-tailpipe traffic emissions; sulphur (S) indicating
      long-range transport; nickel (Ni) and vanadium (V) for mixed oil-burning and
      industry; silicon (Si) for crustal material and potassium (K) for biomass
      burning. Cox regression models with adjustment for potential confounders were
      used for cohort-specific analyses. Combined estimates were determined with random
      effects meta-analyses. RESULTS: Ten cohorts in six countries contributed data on
      227,044 individuals with an average follow-up of 14.9 years with 633 incident
      cases of gastric cancer and 763 of UADT cancer. The combined hazard ratio (HR)
      for an increase of 200 ng/m3 of PM2.5_S was 1.92 (95%-confidence interval (95%
      CI) 1.13;3.27) for gastric cancer, with no indication of heterogeneity between
      cohorts (I2 = 0%), and 1.63 (95%-CI 0.88;3.01) for PM2.5_Zn (I2 = 70%). For the
      other elements in PM2.5 and all elements in PM10 including PM10_S, non
      significant HRs between 0.78 and 1.21 with mostly wide CIs were seen. No
      association was found between any of the elements and UADT cancer. The HR for
      PM2.5_S and gastric cancer was robust to adjustment for additional factors,
      including diet, and restriction to study participants with stable addresses over
      follow-up resulted in slightly higher effect estimates with a decrease in
      precision. In a two-pollutant model, the effect estimate for total PM2.5
      decreased whereas that for PM2.5_S was robust. CONCLUSION: This large multicentre
      cohort study shows a robust association between gastric cancer and long-term
      exposure to PM2.5_S but not PM10_S, suggesting that S in PM2.5 or correlated air
      pollutants may contribute to the risk of gastric cancer.

PMID- 30096613
TI  - Nrf2 expression and function, but not MT expression, is indispensable for
      sulforaphane-mediated protection against intermittent hypoxia-induced
      cardiomyopathy in mice.
AB  - We reported previously that nuclear factor erythroid 2-related factor 2 (Nrf2)
      and metallothionein (MT) play critical roles in preventing intermittent hypoxia
      (IH)-induced cardiomyopathy. In addition, positive feedback regulation between
      Nrf2 and MT is required for the efficient compensative responses of the heart to
      IH. As an activator of Nrf2, sulforaphane (SFN) has attracted attention as a
      potential protective agent against cardiovascular disease. Here, we investigated
      whether SFN can up-regulate cardiac Nrf2 expression and function, as well as MT
      expression, to prevent IH-induced cardiomyopathy, and if so, whether Nrf2 and MT
      are indispensable for this preventive effect. Nrf2-knock-out (Nrf2-KO) or MT-KO
      mice and their wild-type (WT) equivalents were exposed to IH for 4 weeks with or
      without SFN treatment. SFN almost completely prevented IH-induced cardiomyopathy
      in WT mice, and this preventive effect was abolished in Nrf2-KO mice but retained
      in MT-KO mice. In IH-exposed WT mice, SFN induced significant increases in the
      expression levels of Nrf2 and its downstream antioxidant target genes, as well as
      those of MT, but these effects were not seen in IH-exposed Nrf2-KO mice. By
      contrast, KO of MT did not affect the ability of SFN to up-regulate the
      expression of Nrf2 and its downstream antioxidant targets. These results suggest
      that SFN-induced MT expression is Nrf2-dependent, and SFN prevents IH-induced
      cardiomyopathy in a Nrf2-dependent manner, for which MT is dispensable. This
      study provides important information that is relevant to the potential use of SFN
      to prevent IH-induced cardiomyopathy.

PMID- 30096615
TI  - Taurine modulates acute ethanol-induced social behavioral deficits and fear
      responses in adult zebrafish.
AB  - Ethanol (EtOH) is a central nervous system (CNS) depressant drug that modifies
      various behavioral domains (i.e., sociability, aggressiveness, and memory) by
      promoting disinhibition of punished operant behavior and neurochemical changes.
      Taurine (TAU) is a beta-amino sulfonic acid with pleiotropic roles in the brain.
      Although exogenous TAU is found in energy drinks and often mixed with alcohol in
      beverages, the putative risks of mixing TAU and EtOH are poorly explored. Here,
      we investigated whether TAU modulates social and fear responses by assessing
      shoaling behavior, preference for conspecifics, and antipredatory behavior of
      adult zebrafish acutely exposed to EtOH. Zebrafish shoals (4 fish per shoal) were
      exposed to water (control), TAU (42, 150, and 400 mg/L), 0.25% (v/v) EtOH alone
      or in association with TAU for 1 h, and their behaviors were analyzed at
      different time intervals (0-5 min, 30-35 min, and 55-60 min). The effects of TAU
      and EtOH were further tested in a social preference test and during exposure to a
      predator. Both EtOH and TAU co-treated fish showed a higher shoal dispersion,
      while TAU 400/EtOH group shoal area had a similar profile when compared to
      control. However, in the social preference test, TAU 400/EtOH impaired the
      seeking for conspecifics. Regarding fear-like behaviors, TAU-cotreated fish
      showed a prominent reduction in risk assessments when compared to EtOH alone.
      Overall, we demonstrate that TAU modulates EtOH-induced changes in different
      behavioral domains, suggesting a complex relationship between social and fear
      like responses.

PMID- 30096614
TI  - Decreases in GSH:GSSG activate vascular endothelial growth factor receptor 2
      (VEGFR2) in human aortic endothelial cells.
AB  - The angiogenic capacity of local tissue critically regulates the response to
      ischemic injury. Elevated reactive oxygen species production, commonly associated
      with ischemic injury, has been shown to promote phosphorylation of the vascular
      endothelial growth factor receptor 2 (VEGFR2), a critical regulator of
      angiogenesis. Previous data from our lab demonstrated that diminished levels of
      the antioxidant glutathione positively augment ischemic angiogenesis. Here, we
      sought to determine the relationship between glutathione levels and oxidative
      stress in VEGFR2 signaling. We reveal that decreasing the ratio of GSH to GSSG
      with diamide leads to enhanced protein S-glutathionylation, increased reactive
      oxygen species (ROS) production, and enhanced VEGFR2 activation. However,
      increasing ROS alone was insufficient in activating VEGFR2, while ROS enhanced
      VEGF-stimulated VEGFR2 activation at supraphysiological levels. We also found
      that inhibiting glutathione reductase activity is sufficient to increase VEGFR2
      activation and sensitizes cells to ROS-dependent VEGFR2 activation. Taken
      together, these data suggest that regulation of the cellular GSH:GSSG ratio
      critically regulates VEGFR2 activation. This work represents an important first
      step in separating thiol mediated signaling events from ROS dependent signaling.

PMID- 30096616
TI  - Comparison of pregnancy in cattle when non-vitrified and vitrified in vitro
      derived embryos are transferred into recipients.
AB  - The present study was conducted in cattle to test the null hypothesis that the
      pregnancy rate of recipient females is similar when in vitro-derived embryos are
      transferred either fresh (non-vitrified) or after being subjected to
      vitrification. Cumulus-oocyte complexes, collected twice (6 weeks apart) from 10
      donor cows were matured in vitro and inseminated with frozen-thawed sperm from a
      single proven bull per donor collection. Cleaved embryos were cultured in vitro
      until day 7 and any resulting blastocysts were graded for stage [early
      (unexpanded), advanced (expanded, hatching, hatched)] and/or quality and either
      discarded (poor quality), or, if deemed suitable, transferred fresh or vitrified
      for later warming and transfer. All blastocysts were transferred singly to
      oestrus-synchronized cows and pregnancy monitored by transrectal palpation on
      days 35, 60 and 90. From 20 collections, 818 cumulus-oocyte complexes were
      aspirated; however, after grading, only 462 (56.5%) were ranked as suitable
      quality for maturation and insemination. From those 462 complexes inseminated,
      363 (78.6%) cleaved during the process and 243 (52.6%) developed to the
      blastocyst stage with 194 (42.0%) deemed utilizable, of which 85 were vitrified
      and 109 were transferred fresh. There was a median of 13 (range 0-24) utilizable
      blastocysts per cow. Of the 109 non-vitrified blastocysts transferred, there were
      45 (41.3%) and 41 (37.6%) recipients that were detected to be pregnant on day 35
      and day 90, respectively, subsequent to transfer. Thus, an 8.9% abortion rate was
      observed (4/45). Of the 85 transferred vitrified-warmed blastocysts, 34 were
      detected to be pregnant (40.0%) on day 35 following transfer, and all pregnancies
      were maintained at day 90 (0% abortion rate), which was similar to non-vitrified
      transfers (P > 0.05, Chi-square test). There was no significant difference in
      pregnancy rate on day 90 in advanced compared to early blastocysts for either the
      non-vitrified transfers (9/23, 39.1% vs 33/86, 38.3%) or the vitrified transfers
      (30/72, 41.6% vs 4/13, 30.8%) (P > 0.05 in each case). In summary, these data
      show that vitrification of in vitro-derived early and advanced blastocysts is a
      suitable method of cryopreservation of bovine embryos, and, furthermore, that
      subsequent transfer of all vitrified/warmed blastocysts into recipient females
      results in pregnancy rates no different to those attained by non-vitrified
      transfers into recipient females.

PMID- 30096618
TI  - Spermatogonial stem cells differentiation and testicular lobules formation in a
      seasonal breeding teleost: The evidence from the heat-induced masculinization of
      genetically female Japanese flounder (Paralichthys olivaceus).
AB  - Germ cells undergo a series of cellular changes including differentiation,
      mitosis, meiosis and maturation, and eventually develop into a large number of
      functional gametes. The available data regarding teleost gametogenesis in
      seasonal batch spawners is limited. In this study, we investigated
      spermatogenesis with special attention on spermatogonia differentiation using
      heat-induced masculine juveniles of genetically female Japanese flounder.
      Meanwhile, the Nanos2 expression had been detected by immunohistochemistry for
      analysis of spermatogonial stem cells (SSCs) distribution. Spermatogonia began
      mitosis at 35 dph, and basement membrane firstly appeared and gradually
      surrounded and separated the spermatogonia (type A) into single and paired
      status. At this period, the spermatogonia continuously maintained mitotic
      proliferation. As a result, the number of spermatogonia including isolated and
      clusters (2-8 spermatogonia) significantly increased in the presumptive testes.
      From 85 dph to 120 dph, with the mitosis of spermatogonia, germline acinar
      clusters formed. In the clusters, type A spermatogonia differentiated into type
      B, and multi-spermatogonia surrounded by several sertoli cell formed cysts,which
      represented the formation of lobular precursors. After that, type B spermatogonia
      began meiosis, which indicated the initiation of spermatogenesis. In adult
      testes, most type A spermatogonia distributed in the peripheral region and a few
      clung to a basement membrane in the internal germinal epithelium. Various
      spermatogenic cysts with germ cells in different developmental stages existed in
      a testicular lobules, moreover the germ cells in earlier stages resided in the
      distal termini, and the advanced stages were adjacent to the spermatic duct of
      testes. Therefore, the testes of Japanese flounder belonged to an intermediated
      distribution of SSCs, which might contribute greatly to multiple spermiation
      during breeding season. These findings would improve the understanding the
      mechanisms of SSCs differentiation and testicular development, and may be of
      great value in future studies of the spermatogenesis regulation.

PMID- 30096617
TI  - Interferon-tau stimulated gene expression: A proxy to predict embryonic mortality
      in dairy cows.
AB  - The embryonic mortality in cows is a growing concern for an ever-expanding dairy
      industry. The current study was an attempt to shorten the open period of dairy
      cows having suffered embryonic loss by diagnosing them at an earlier stage. The
      blood samples were collected from the Karan Fries (KF) cows on days 0 (day of
      AI/estrus), 4, 8, 12, 14, 16, 18, 21, 24, 28, 35 and 42 post insemination. The
      experimental animals were then categorized into pregnant (P), conception
      failure/early embryonic mortality (EEM) and late embryonic mortality cows (LEM),
      based on progesterone assay, ultrasonography and per-rectal palpation. There were
      6 animals in each group. The plasma progesterone was higher in pregnant than EEM
      and LEM cows. Plasma Interferon-tau concentration was significantly (p < 0.05)
      lower in LEM than pregnant cows where it could be detected from day 14-21 but was
      non-detectable in EEM cows. The mRNA expression of ISG15, OAS1, MX1 and MX2 in
      blood neutrophils was significantly (p < 0.05) higher from day 8-42 as against
      day 0 in pregnant cows. The highest expression was observed around day 18-21 in
      pregnant cows. The ISG15, OAS1, MX1 and MX2 mRNA expression was significantly (p
      < 0.05) higher from day 4-42 as compared to day 0 in LEM cows, whereas in EEM
      cows the expression stayed close to that of day 0 (1.00 +/- 0.00). The mRNA
      expression of ISG15, OAS1, MX1 and MX2 started to decline from day 24 onwards.
      The degree of expression of Interferon-tau stimulated genes was higher in
      pregnant and LEM cows than EEM cows. The study reveals that the Interferon tau
      stimulated gene expression in neutrophils can act as peripheral biomarkers for
      detecting the embryonic mortality in dairy cows.

PMID- 30096620
TI  - The presence of two ovulatory follicles at timed artificial insemination
      influences the ovulatory response to GnRH in high-producing dairy cows.
AB  - This study sought to examine the impact of the presence of two co-dominant
      (ovulatory) follicles at the time of artificial insemination (AI) on the
      ovulatory response to GnRH given in a fixed-time AI protocol. The study
      population comprised 622 lactating dairy cows: 306 (49.2%) with a single
      follicle, 198 (31.8%) with two bilateral follicles (one follicle per ovary) and
      118 (19%) with two unilateral follicles (same ovary). Based on odds ratios, cows
      with two bilateral or unilateral follicles were less likely (by factors of 0.09
      and 0.11, respectively) to undergo ovulation failure compared with cows with one
      follicle (P = 0.01 and P = 0.02, respectively); the likelihood of ovulation
      failure decreased 0.75 times with every one-mm increase in follicle diameter for
      cows with a single follicle, whereas individual follicle diameter was not related
      to ovulation failure in cows with two bilateral follicles (P = 0.001). The
      likelihood of double ovulation decreased 0.7 times with every one-mm diameter
      difference between the larger and smaller follicle for all cows with two
      follicles (P = 0.001), whereas cows with two unilateral follicles showed a higher
      (P < 0.05) double ovulation rate than cows with two bilateral follicles. In 116
      (58.6%) of the cows with two bilateral follicles, only the larger follicle
      ovulated in 59.5% cows, whereas only the smaller one ovulated in the remaining
      40.5% cows. In these cows, a one-mm size difference between the larger and the
      smaller follicle gave rise to a 1.12-fold increase in the ovulation failure rate
      for the larger follicles (P = 0.0001). Cows with two bilateral follicles were
      more likely (by a factor of 1.5) to conceive than cows with one follicle (P =
      0.001). Significant right-left differences were not found in cows with two
      bilateral follicles, whereas the right ovary was more active than the left in the
      remaining cows. Our results indicate that cows with two co-dominant follicles at
      AI show different ovulation patterns to those with one dominant follicle. A
      higher rate of ovulation failure was observed among cows with one follicle than
      cows with two follicles, whereas the conception rate was higher for cows with two
      bilateral follicles than for the remaining cows. In cows with two follicles,
      double ovulations along with ovulation of the smaller follicle were related to
      the least size difference between the larger and smaller follicle.

PMID- 30096619
TI  - Administration of slow release exogenous melatonin modulates oxidative stress
      profiles and in vitro fertilizing ability of the cryopreserved mithun (Bos
      frontalis) spermatozoa.
AB  - Mithun (Bos frontalis) is a unique domestic free range bovine species of North
      Eastern hilly regions of India. The present study was designed to assess the
      seasonal effect of slow release exogenous melatonin (MT) implant on semen quality
      parameters (SQP) and in vitro zona binding ability (IVZ) of spermatozoa. The
      experimental animals were divided into Gr I: Control (n = 5) and Gr II: Treatment
      (n = 5; melatonin implant @ 18mg/50 kg bwt). A total of 20 semen samples/group in
      winter, spring, autumn and summer seasons (n = 160), twice per week were
      collected. Following cryopreservation, samples were evaluated for motility
      parameters (forward progressive, mobility & velocity by computer assisted sperm
      analyser (CASA), viability, acrosome integrity, plasma membrane and nuclear
      abnormality, functional status of mitochondria, enzymatic, antioxidant and
      oxidative profiles, and IVZ. The study revealed significant (p < 0.05)
      improvement in total motility, viability, acrosome-, plasma membrane-, and
      nuclear-integrity, and antioxidant profiles; with highest values in spring and
      lowest in summer season in the fresh semen in Gr II than the Control. A
      significant (p < 0.05) improvement in motility parameters, membrane potential of
      mitochondria, antioxidant profiles and reduction in sperm and nuclear
      abnormalities, leakage of intracellular enzymes and oxidative stress and IVZ
      index & binding percentage in post-thaw semen samples in melatonin supplemented
      than in un-supplemented control group was observed. It can be concluded from the
      study that slow-release melatonin supplementation can be effectively utilized to
      improve the antioxidant profiles and reduction of oxidative stress, with
      cascading beneficial effects on semen quality parameters and fertility status of
      the mithun bull.

PMID- 30096622
TI  - Annexin A1, FPR2/ALX, and inflammatory cytokine expression in peritoneal
      endometriosis.
AB  - To characterize Annexin A1 (ANXA1), FPR2/ALX and cytokines expression in
      peritoneal endometriosis and to clarify their role in its etiology, a cross
      sectional study was performed with forty women in reproductive age (22 patients
      with endometriosis and 18 control women) that had undergone laparoscopic surgery.
      Peritoneal biopsy and fluid aspirations from endometriosis and control samples
      were analyzed for the expression of ANXA1, FPR2/ALX and cytokines. ANXA1 and FPR2
      / ALX levels were measured by Western blotting and interleukin 1beta (IL-1beta),
      interleukin 4 (IL-4), interleukin 6 (IL-6), and interleukin 10 (IL-10) levels
      were quantified by enzyme-linked immunosorbent assay (ELISA). The present study
      identified the presence in human peritoneal tissue of ANXA1 and FPR2 / ALX both
      in healthy condition and in women with peritoneal endometriosis, however, was
      lower in endometriosis samples than in control samples. By quantifying the IL-6
      and IL-1beta cytokines in the peritoneal fluid by ELISA, this study identified a
      higher IL-6 concentration in endometriosis group, but no significative difference
      in IL-1beta levels. The IL-4 and IL-10 levels could not be detected. These
      results indicate that the reduction of the inflammatory resolution mediators
      could be responsible for the inflammatory process perpetuation, maintenance and
      worsening of endometriosis.

PMID- 30096621
TI  - Impotentia generandi in male dromedary camels: FSH, LH and testosterone profiles
      and their association with clinical findings and semen analysis data.
AB  - Impotentia generandi (IG) is a major problem in male dromedary camels. The
      objective of this research was to characterize the FSH, LH and testosterone
      profiles and their association with clinical findings and semen characteristics
      in IG-male dromedaries. Semen was collected by electroejaculation from camels
      with IG (n = 17) and from a fertile group (FERT, n = 5) and was evaluated for
      motility, viability, abnormality and concentration. According to their sperm
      counts, the IG-camels were categorized into three groups: those with normal sperm
      concentration (IG-NC, n = 8), those with oligospermia (IG-OLIGO, n = 5) and those
      with azoospermia (IG-AZOO, n = 4). Jugular blood was collected from all camels
      for analysis of FSH, LH and testosterone (T) concentrations. Results showed that
      the FSH, LH and T levels were higher in the IG-OLIGO and IG-AZOO groups than in
      the FERT and IG-NC groups (P < 0.05). The IG-camels with small testes showed
      lower sperm counts (P < 0.01) and greater FSH and T levels (P < 0.05) than the IG
      camels with normal-sized testes. Inverse relationships were observed between the
      sperm counts and both the FSH and the LH levels (P < 0.05). In conclusion, the IG
      dromedary camels with oligo- and azoospermia were characterized by high serum
      levels of FSH, LH and T, indicating a condition of spermatogenic failure. In
      addition, inverse correlations were observed between these hormones and
      testicular size and sperm count.

PMID- 30096623
TI  - Bullying victimization and depressive symptoms in adolescence: The moderating
      role of parent-child conflicts among boys and girls.
AB  - INTRODUCTION: The association between bullying victimization and depressive
      symptoms has been studied extensively over the years. Among the variables studied
      as having an impact on this association were different characteristics of the
      parent-child relationship. The current study was the first to specifically
      examine parent-child conflicts as a moderator in the association between
      victimization and depressive symptoms among adolescents. In addition, it was the
      first to examine the roles of the child and parent's gender in this moderation.
      METHODS: 505 7th-9th graders from two schools in two different cities across
      Israel (mean age = 12.736, SD = 0.8154) participated in this study. 223 (44.2%)
      of the participants were male. The participants filled out a battery of self
      report questionnaires assessing the different study's variables. RESULTS:
      Significant gender differences were found: among girls, the association between
      bullying victimization and depressive symptoms was stronger when the level of
      parent-child conflicts was high, while among boys, it was stronger when the level
      of conflicts was low. CONCLUSIONS: Our results indicate that the psychological
      outcomes for victims depend on their relationship with their parents. Bullying
      intervention programs should include the victims' parents. Furthermore,
      intervention programs should be designed to fit the different needs of girls and
      boys.

PMID- 30096624
TI  - "I wonder if I did not mess up....": Shame and resistance among women with
      epilepsy in Cape Town, South Africa.
AB  - PURPOSE: Literature shows that there has been more attention paid to epilepsy
      stigma, with less focus on issues of shame and resistance. This article provides
      an in-depth understanding of processes of shame and resistance strategies which
      emerged from the analysis of individual stories of four adult Xhosa -speaking
      women with epilepsy in an urban Black township in Cape Town, South Africa.
      METHODS: Our data collection method involved individual in-depth face to face
      interviews using a semi-structured interview guide adapted from Kleinman's
      Explanatory Model Framework. This framework enabled participants to openly share
      their experiences and perspectives of living with the illness. Their audio
      recorded qualitative interview data were transcribed and analysed using a
      thematic data analysis method. RESULTS: Two main themes about processes of shame
      and resistance strategies emerged. Two women stories provided insights about the
      different types of emotions related to shame such as feelings of anger, guilt,
      regret and grief. Resistance strategies against actions of discrimination, unfair
      treatment and abuse were evident from the stories of the other two women with
      epilepsy. Being a bully was another form of violent strategy to fight
      victimization. CONCLUSION: The findings demonstrate a need for a closer
      examination of these issues in future epilepsy studies in the study setting - and
      these should also be examined among men with epilepsy.

PMID- 30096625
TI  - Randomized controlled trials of antiepileptic drugs for the treatment of post
      stroke seizures: A systematic review with network meta-analysis.
AB  - OBJECTIVE: To determine the best available evidence on the efficacy and
      tolerability of antiepileptic drugs (AEDs) used to treat poststroke seizures and
      epilepsy. METHODS: MEDLINE, Embase, CENTRAL, ClinicalTrials.gov and Opengrey.eu
      were searched for RCTs of AEDs used to treat post-stroke epilepsy. The following
      outcomes were considered: seizure freedom; occurrence of adverse effects (AEs);
      withdrawal for AEs. The methodological quality was assessed according to the
      Cochrane Handbook for Systematic Reviews of Interventions. Adjusted indirect
      comparisons were made between each AED using controlled-release carbamazepine (CR
      CBZ) as common comparator. RESULTS: Only 2 RCTs were included, one comparing
      levetiracetam (LEV) with CR-CBZ and the other comparing lamotrigine (LTG) with CR
      CBZ. No significant difference was found in seizure freedom between either LEV or
      LTG and CR-CBZ. Occurrence of AEs were lower for LEV and LTG than for CR-CBZ.
      Indirect comparisons showed no difference between LEV and LTG for seizure freedom
      (OR 0.86; 95%CI: 0.15-4.89). Occurrence of AEs was higher for LEV than for LTG
      (OR 6.87; 95%CI: 1.15-41.1). For withdrawal rates due to AEs, we found a large
      width and asymmetrical distribution of confidence intervals around the obtained
      OR of 10.8 (95% CI: 0.78-149.71). CONCLUSIONS: Direct and indirect comparisons
      did not find a difference in seizure freedom between the various AEDs, probably
      because of the small number of patients included. LEV and LTG appears better
      tolerated than CR-CBZ and LEV seems associated with more AEs than LTG. Further
      studies are required to provide robust evidence on efficacy and tolerability of
      AEDs for treating poststroke epilepsy.

PMID- 30096626
TI  - Integration of bioinformatics and experiments to identify TP53 as a potential
      target in Emodin inhibiting diffuse large B cell lymphoma.
AB  - Non-Hodgkin's Lymphoma (NHL) is a group of lymphoid malignancies with
      unsatisfactory treatment effect in some aggressive subtypes, including diffuse
      large B cell lymphoma (DLBCL). Emodin is an anthraquinone with potent anti-cancer
      activities. However, the molecular mechanism of Emodin repressing aggressive NHL
      remains to be revealed in detail. This study delineated the active mechanism of
      Emodin action in aggressive NHL by using bioinformatics analysis and in vitro
      assay. 4 Emodin's primary direct protein targets (DPT) were identified and the
      DPTs-associated proteins/genes were predicted. Those Emodin-related
      proteins/genes were subject to enrich Emodin-associated pathways, from which 3
      significantly NHL-related signal pathways were refined identified. Advanced
      integrated analysis exhibited TP53 and PI3K as the significant molecule and
      pathway by which Emodin may function in NHL. To verify those bioinformatics
      findings, effects of Emodin and E35, a novel derivative of emodin were
      investigated on DLBCL cell lines SU-DHL4. Emodin and E35 suppressed proliferation
      and induced apoptosis of SU-DHL4 cells in a time- and dose-dependent manner.
      Emodin and E35 declined TP53 protein expression and decreased phosphorylation of
      PI3K/AKT protein in a dose-dependent manner. All of above showed that combined
      bioinformatics analysis with experiments offered a novel approach for outlining
      the mechanisms of Emodin action in DLBCL with convenience and integrity.

PMID- 30096627
TI  - Rational in silico design of novel alpha-glucosidase inhibitory peptides and in
      vitro evaluation of promising candidates.
AB  - Treatment of type 2 diabetes is achieved through the inhibition of carbohydrate
      hydrolyzing enzymes such as alpha-glucosidase and alpha-amylase. The present
      study was conducted to identify novel alpha-glucosidase inhibitory peptides and
      to validate the alpha-glucosidase and alpha-amylase inhibitory activities of two
      promising candidates. A total of 4210 potential alpha-glucosidase inhibitory
      peptides with 3-5 amino acid residues were designed and individually subjected to
      in silico simulated gastrointestinal (GIT) digestion using the BIOPEP database.
      Subsequently, 844 GIT resistant peptides were then subjected to molecular docking
      using Autodock Vina to determine their binding free energy against human alpha
      glucosidase (PDB ID: 3L4Y). Among all the peptides, SVPA and SEPA were found to
      have the lowest binding free energies of -8.7 and -8.6 kcal/mol, respectively.
      Docking of SVPA and SEPA on human alpha-amylase (PDB ID, 4GQR) identified that
      both peptides also bind to alpha-amylase with binding energies of -6.5 and -6.9
      kcal/mol, respectively. Hydrogen bond interactions were critical for the binding
      of both peptides to the alpha-glucosidase and alpha-amylase. In vitro, SVPA and
      SEPA inhibited alpha-glucosidase and alpha-amylase activities with IC50 values
      several fold lower than acarbose except for SVPA that had a significantly higher
      (p <  0.05) IC50 value than acarbose against alpha-glucosidase. Lineweaver-Burk
      analyses revealed that SVPA was an uncompetitive inhibitor of the two enzymes,
      while SEPA inhibited alpha-glucosidase and alpha-amylase non-competitively and
      uncompetitively, respectively. This study has identified two novel and active
      alpha-glucosidase inhibitory peptides that could resist GIT digestion and
      therefore, have the potential to retard postprandial hyperglycemia in diabetic
      patients.

PMID- 30096628
TI  - Amentoflavone suppresses hepatocellular carcinoma by repressing hexokinase 2
      expression through inhibiting JAK2/STAT3 signaling.
AB  - Hepatocellular carcinoma (HCC) has become a burden on public health worldwide.
      Therefore, development of novel therapeutic agents for managing HCC is
      imperative. Amentoflavone (AF), a flavonoid compound extracted from Selaginella
      tamariscina Spring, reportedly has anti-neoplastic activities. The aim of this
      study was to investigate the role of AF in HCC and the underlying mechanism of
      action. We found that AF decreased cell viability in a dose-dependent manner in
      both HCC cell lines but did not affect the viability of a normal hepatic cell
      line. The anti-growth effect of AF against HCC was also confirmed in the
      xenograft model. Standard histological examination of the xenograft tissues also
      revealed minimal in vivo toxicity of AF. The In vitro and in vivo models also
      provided evidence of the pro-apoptotic activity of AF. In addition, AF
      significantly inhibited glycolysis via HK2 repression; further dissection of the
      underlying mechanism revealed that AF downregulated HK2 by generating ROS and
      hence inhibiting the JAK2/STAT3 signaling pathway. In conclusion, AF induced
      apoptosis and inhibited glycolysis in HCC by targeting HK2. Our findings provide
      preliminary experimental data that support further investigation of the
      therapeutic efficacy of AF in HCC.

PMID- 30096629
TI  - Anti-exercise-fatigue and promotion of sexual interest activity of total
      flavonoids from wasps drone-pupae in male mice.
AB  - The aim of this research was to evaluate the anti-exercise-fatigue and promotion
      of sexual interest of total flavonoids from drone pupae of wasps. DPTF was
      prepared by ethanol extracting and its extraction conditions were optimized by
      response surface methodology. Then, anti-exercise-fatigue and promotion of sexual
      interest of DPTF were evaluated. The optimums extraction conditions by RSM were
      ethanol concentration 65%, extraction time 3 h and solid-to-liquid 20:1(mL/g). No
      mortality and general symptoms of toxicity were observed in the DPTF treated
      mice(1 g/kg,3 g/kg,5 g/kg body weight) the body weight and food consumption were
      not significantly changed compared with the normal control group. The relative
      weights of main organ did not markedly change. DPTF can significantly extend the
      duration of the swimming time to exhaustion and the times of capture the female
      in mice, decrease BUN, LAC and Cr levels, increase LG, GG and T activities in the
      DPTF treated mice. The dose of 5 g/kg body weight is the optimal dose for anti
      exercise-fatigue activity and promotion of sexual interest in male mice. In
      conclusion, DPTF is promising traditional natural-based therapeutic remedy for
      relieving exercise-fatigue with high safety.

PMID- 30096630
TI  - A case of bone fracture with callus on the right femur of a chicken (Gallus
      gallus domesticus, L. 1758) from the ancient site of Dharih, Jordan.
AB  - Archaeozoology provides bones, which quite regularly present traces of fractures.
      These fractures are more or less at an advanced level of healing and bear witness
      to traumas or pathologies. These cases of palaeopathology are not always the
      subject of publications, which further restricts our knowledge about them. This
      short note allows the scientific community to be aware of an original case from
      an archaeological context in Jordan of a fracture on a hen's femur, consolidated
      by a callus and with displacement of the distal ends. Beyond the "anecdotal"
      aspect, and without imagining the circumstances in which the fracture occurred,
      the animal survived.

PMID- 30096631
TI  - Ring depressions in cattle horncores as indicators of traction use - a cautionary
      note.
AB  - In this short communication we call attention to the discovery of a ring
      depression (a circumferential constriction) in the horncore of a feral bull. This
      discovery casts doubt on the attribution of similar lesions in archaeological
      deposits as conclusive evidence of 'cord impressions' resulting from yoking or
      reining cattle for traction. Drawing upon evidence of horncore depressions in
      other species, we suggest that they reflect metabolic problems following horn
      development; additional research is required to test this hypothesis.

PMID- 30096632
TI  - A study about color normalization methods for histopathology images.
AB  - Histopathology images are used for the diagnosis of the cancerous disease by the
      examination of tissue with the help of Whole Slide Imaging (WSI) scanner. A
      decision support system works well by the analysis of the histopathology images
      but a lot of problems arise in its decision. Color variation in the
      histopathology images is occurring due to use of the different scanner, use of
      various equipments, different stain coloring and reactivity from a different
      manufacturer. In this paper, detailed study and performance evaluation of color
      normalization methods on histopathology image datasets are presented. Color
      normalization of the source image by transferring the mean color of the target
      image in the source image and also to separate stain present in the source image.
      Stain separation and color normalization of the histopathology images can be
      helped for both pathology and computerized decision support system. Quality
      performances of different color normalization methods are evaluated and compared
      in terms of quaternion structure similarity index matrix (QSSIM), structure
      similarity index matrix (SSIM) and Pearson correlation coefficient (PCC) on
      various histopathology image datasets. Our experimental analysis suggests that
      structure-preserving color normalization (SPCN) provides better qualitatively and
      qualitatively results in comparison to the all the presented methods for breast
      and colorectal cancer histopathology image datasets.

PMID- 30096633
TI  - Combination of hemoglobin and low-flow duration can predict neurological outcome
      in the initial phase of out-of-hospital cardiac arrest.
AB  - PURPOSE: To predict neurological outcome following out-of-hospital cardiac arrest
      (OHCA) using a combination of hemoglobin (Hb) and low-flow duration (LFD).
      MATERIALS AND METHODS: We retrospectively examined 131 patients (75 +/- 13 years,
      64 men) with return of spontaneous circulation (ROSC) following non-traumatic
      OHCA. The LFD was the duration from the start of cardiopulmonary resuscitation to
      ROSC. To obtain the Hb/LFD value, we divided the Hb level by the LFD.
      Multivariate logistic regression analyses were performed to predict full
      neurological recovery (FNR), defined as Cerebral Performance Category scale
      scores of 1 or 2 at discharge. RESULTS: Nineteen patients (15%) achieved FNR.
      Patients with FNR had high Hb levels (14.9 +/- 2.1 vs. 11.3 +/- 2.7 g/dl, p =
      0.001) and short LFDs (10 [5, 18] vs. 35 [28, 43] min, p = 0.001). Multivariate
      analyses identified the initial ventricular fibrillation rhythm and Hb/LFD as
      significant predictors for FNR (odds ratio: 24.9, 3.58; p = 0.001, 0.02,
      respectively). Receiver operating characteristic (ROC) curve analyses indicated
      that a high Hb/LFD predicted FNR (cut-off value: 0.50, sensitivity: 94.7%,
      specificity: 84.5%, area under the curve: 0.933). CONCLUSIONS: Patients with FNR
      following OHCA had high Hb levels and short LFDs; the Hb/LFD value significantly
      predicted FNR.

PMID- 30096634
TI  - Decompressive laparotomy for the treatment of the abdominal compartment syndrome
      during extracorporeal membrane oxygenation support.

PMID- 30096635
TI  - Noradrenaline modifies arterial reflection phenomena and left ventricular
      efficiency in septic shock patients: A prospective observational study.
AB  - PURPOSE: To determine whether noradrenaline alters the arterial pressure
      reflection phenomena in septic shock patients and the effects on left ventricular
      (LV) efficiency. MATERIAL AND METHODS: Thirty-seven septic shock patients with a
      planned change in noradrenaline dose. Timing and magnitude (Reflection Magnitude
      and Augmentation Index) of arterial reflections were evaluated. Total, steady,
      and oscillatory LV power (also expressed as fraction of the total power),
      subendocardial viability ratio (SEVR), energy efficiency and transmission ratios
      were used as a marker of LV efficiency. RESULTS: An incremental change in
      noradrenaline increased Reflection Magnitude [0.28(0.09) to 0.31(0.1],
      Augmentation Index [-6.4(23.6) to 4.8(20.7)%], and LV total power [0.79(IQR:0.47
      1) to 0.98(IQR:0.57-1.27)W], all p < 0.001; whereas decreased arrival time of
      reflected waves [from 95(87 to 121) to 83(79 to 101)ms; p < 0.001]. Variables of
      LV performance showed a decreased efficiency: oscillatory fraction and energy
      efficiency ratio increased [20.9(5.7) to 22.8(4.9)%, and 8.2(1.7) to 10.1(2)
      mW.min.litre-1; p < 0.001, respectively]; and energy transmission ratio and SEVR
      decreased [73.8(9.9) to 72(9.8)% and 146(IQR:113-188) to 143(IQR:109-172)%, p =
      0.003 and p = 0.041, respectively]. CONCLUSIONS: Noradrenaline increased
      reflection phenomena, increasing LV workload and worsening LV performance in
      septic shock patients. These conditions could explain the detrimental effects
      during long-term use of noradrenaline.

PMID- 30096636
TI  - Why smokers avoid cigarette pack risk messages: Two randomized clinical trials in
      the United States.
AB  - BACKGROUND: Message avoidance (e.g., trying not to look at the message) may be
      motivated by reactance, a maladaptive rejection of the message. An alternative
      view is that avoidance indicates that a message is eliciting fear and other
      negative affect, thereby increasing the likelihood of behavioral change. We
      sought to identify which psychological mechanism-reactance or fear and other
      negative affect-explains message avoidance. We also examined whether avoidance
      was associated with more forgoing or butting out of cigarettes. METHOD: Trial 1
      randomly assigned 2149 adult U.S. smokers to receive either pictorial warnings
      (intervention) or text-only warnings (control) on their cigarette packs for four
      weeks in 2014 and 2015. Trial 2 randomly assigned 719 adult U.S. smokers to
      receive either messages about toxic chemicals in cigarette smoke (intervention)
      or messages about not littering cigarette butts (control) for three weeks in 2016
      and 2017. Negative affect included fear, anxiety, disgust, sadness, and guilt.
      Reactance included perceived threat to freedom, anger, and counterarguing.
      RESULTS: Intervention messages led to greater message avoidance in both trials
      (both p < .001). In Trial 1, intervention messages elicited greater negative
      affect, which in turn was associated with greater avoidance (mediated effect =
      0.21, p < .001). In contrast, reactance explained only a small part of the effect
      in Trial 1 (mediated effect = 0.03, p < .001). Similarly, in Trial 2,
      intervention messages elicited greater negative affect, which was associated with
      more avoidance (mediated effect = 0.12, p < .001); reactance did not explain any
      of the effect. In both trials, avoidance was associated with more forgoing or
      butting out of cigarettes (ps < .001). CONCLUSIONS: Smokers may avoid cigarette
      pack risk messages because they evoke aversive types of emotion. These studies
      add to a growing body of evidence that, in the context of cigarette pack
      messages, avoidance is not a form of defensive processing but instead a sign of
      deeper processing.

PMID- 30096638
TI  - Comparing the contribution of prescribed opioids to opioid-related
      hospitalizations across Canada: A multi-jurisdictional cross-sectional study.
AB  - BACKGROUND: The Canadian opioid crisis is a complex, multifaceted problem
      involving prescribed, diverted and illicitly manufactured opioids. This study
      sought to characterize the contribution of prescribed opioids to opioid-related
      hospitalizations in Canada. METHODS: We conducted a cross-sectional study of all
      individuals who were admitted to hospital for opioid toxicity in British Columbia
      (BC), Manitoba and Ontario between April 2015 and March 2016. We used
      prescription claims to ascertain active prescription opioid use at time of
      hospital admission. In secondary analyses, we defined recent opioid prescriptions
      as those that were dispensed in the 30 and 180 days up to and including
      admission, and the prevalence of active co-prescription of benzodiazepines with
      opioids at time of overdose. RESULTS: We identified 2599 instances of opioid
      toxicity over the study period. In BC, 34.1% of hospital visits for overdose
      occurred in people with an active opioid prescription, compared to 52.2% (47 of
      90) in Manitoba and 52.8% (804 of 1524) in Ontario. However, active opioid
      prescriptions prior to overdose varied significantly by age and sex. Co
      prescription of opioids and benzodiazepines prior to overdose ranged from 17.1%
      in BC to 35.6% in Manitoba. CONCLUSIONS: There remains an important ongoing
      contribution of prescribed opioids to overdoses across Canada, but non-prescribed
      opioids play a growing role, particularly in BC. These findings underscore the
      importance of more judicious opioid prescribing, harm reduction programs, and
      improved access to addiction care for people with an opioid use disorder.

PMID- 30096637
TI  - Effect of electronic screening and brief intervention on hazardous or harmful
      drinking among adults in the hospital outpatient setting: A randomized, double
      blind, controlled trial.
AB  - BACKGROUND: Most trials of electronic alcohol screening and brief intervention (e
      SBI) have been conducted in young people. The aim of this study was to evaluate
      the effect of e-SBI in adults with hazardous or harmful drinking. METHODS: This
      individually randomized, parallel, two-group, double-blind controlled trial was
      conducted in the outpatient department of a large public hospital in Australia.
      Consenting adults who scored 5-9 on the AUDIT-C (837/3225; 26%) were randomized
      in a 1:1 ratio by computer to screening alone (442/837; 53%) or to 10 min of
      assessment and personalized feedback on their alcohol consumption (comparisons
      with medical guidelines and age and sex-specific norms), peak blood alcohol
      concentration, expenditure on alcohol, and risk of alcohol dependence (395/837;
      47%). The two primary outcomes, assessed six months after randomization, were the
      number of standard drinks (10 g ethanol) consumed by participants in the last
      seven days and their AUDIT score. RESULTS: 693/837 (83%) and 635/837 (76%)
      participants were followed-up at 6 and 12 months, respectively. There was no
      statistically significant difference between the groups in the median number of
      standard drinks consumed in the last seven days (intervention: 12; control: 10.5;
      rate ratio, 1.12 [95% confidence interval, 0.96-1.31]; P = .17) or in their
      median AUDIT score (intervention: 7; control: 7; mean difference, 0.28 [-0.42 to
      0.98]; P = .44). CONCLUSION: These results do not support the implementation of
      an e-SBI program comprising personalized feedback and normative feedback for
      adults with hazardous or harmful drinking in the hospital outpatient setting.

PMID- 30096639
TI  - Cue reactivity and opioid blockade in amphetamine dependence: A randomized,
      controlled fMRI study.
AB  - BACKGROUND: The opioid antagonist, naltrexone, has been shown to reduce the risk
      of relapse in amphetamine dependence, but the mechanisms behind this effect are
      not well understood. We aimed to investigate if naltrexone attenuates cue
      reactivity and craving in amphetamine dependence. METHODS: Forty men with severe,
      intravenous amphetamine dependence were randomized to one dose of naltrexone (50
      mg) or placebo. In a BOLD fMRI cue reactivity paradigm, they were exposed to drug
      related and neutral films and gave subjective ratings of craving after each film.
      Twenty-nine patients left data of sufficient quality to be included in the final
      analysis. RESULTS: The drug-related films elicited strong subjective craving and
      BOLD activations of the striatum, cingulate cortex, and occipito-temporal visual
      attention networks. Longer history of amphetamine use was associated with greater
      activations of the prefrontal cortex. Naltrexone as compared to placebo had no
      significant effects on brain activations or subjective ratings. CONCLUSION:
      Patients with severe stimulant use disorder exhibit strong neural cue reactivity,
      the patterns of which are modulated by duration of drug use. In this sample, we
      found no evidence for any effects of naltrexone on cue reactivity.

PMID- 30096640
TI  - Parent-based interventions on adolescent alcohol use outcomes: A systematic
      review and meta-analysis.
AB  - BACKGROUND: The effects of parent-based interventions on adolescent alcohol use
      are unclear, including what factors moderate intervention effects. This study
      examines the effects of parent-based interventions on adolescent alcohol use and
      whether the treatment effects vary by participants' characteristics and
      intervention characteristics. METHODS: Eleven electronic databases and relevant
      studies' references were searched for eligible studies published before March
      2017. Randomized controlled trials investigating the efficacy of any parent-based
      intervention for alcohol use outcomes among adolescents up to 18 years old were
      eligible for review. Two reviewers independently conducted screening, data
      extraction, and risk of bias assessment. Robust variance estimation in meta
      regression was used to analyze treatment effect size estimates and to conduct
      moderator analysis. RESULTS: Twenty studies were included in the meta-analysis.
      The average treatment effect size across all drinking outcomes, with 44 effect
      sizes from 20 studies, was g = -0.23 with a 95% confidence interval [-0.35, 
      0.10] which is statistically significant. Parent-based interventions appreared to
      have larger mean effect sizes on adolescent drinking intention than binge
      drinking. Interventions targeting both general and alcohol-specific parenting
      strategies had larger average effect sizes than interventions targeting alcohol
      specific parenting only. CONCLUSIONS: This meta-analysis found evidence of parent
      based interventions' efficacy in preventing or reducing adolescent alcohol use.

PMID- 30096641
TI  - Artificial creation of Chlorella pyrenoidosa mutants for economic sustainable
      food production.
AB  - To improve the economic viability of Chlorella as feedstock for food commodities,
      a serial of concentrations of low-cost sweet sorghum juice (SSJ), alternative to
      glucose, were used for the fermentation of Chlorella pyrenoidosa. A high biomass
      and protein production (8.91 g L-1 biomass and 4.52 g L-1 protein) was revealed
      with 20% SSJ. To further increase productivity, heavy-ion irradiation-mediated
      mutagenesis was employed to create mutants where a strain K05, with desired
      phenotypes (increased biomass and protein production in pilot-scale
      fermentation), was screened. Compared with the parental strain, the production of
      biomass, proteins, and chlorophylls of mutant K05 increased by 11.6%, 31.8%, and
      7.6%, respectively. Production capacities under industrial scale (two-ton)
      further pinpoint the stability and scalability of mutant K05. These results
      suggest that advances in cultivation techniques coupled with artificial strain
      improvement will further promote microalgae as an attractive platform of
      functional food.

PMID- 30096642
TI  - Using Fe(III)-coagulant-modified colloidal gas aphrons to remove bio-recalcitrant
      dissolved organic matter and colorants from cassava distillery wastewater.
AB  - Efficient removal of bio-recalcitrant dissolved organic matter (DOM) and
      colorants is essential for discharging or reusing the distillery wastewater. The
      present work adopted a novel microbubble system - Fe(III)-coagulant-modified
      colloidal gas aphrons (CGAs) in flotation as tertiary treatment of the bio
      chemically treated cassava distillery wastewater. Approximately 93% of bio
      recalcitrant color and around 79% of dissolved organic carbon (DOC) were removed
      at the initial pH of 9.0 and 7.1, individually. The modified CGAs exhibited
      strong ability of complexation and electrostatic attraction of the polyanions of
      DOM and colorants. But the 1-10 kDa DOM was found to be resistant to the CGA
      capture. Compared with directly dosing coagulant, the Fe(III)-coagulant-modified
      CGAs consumed ~47% and ~21% less coagulant to achieve the optimum decoloration
      efficiency and DOC removal, respectively. In the flotation with Fe(III)-coagulant
      modified CGAs, the coagulant-dosing system could be omitted while the coagulant
      utilization was improved.

PMID- 30096643
TI  - Bioethanol production from wheat straw by phosphoric acid plus hydrogen peroxide
      (PHP) pretreatment via simultaneous saccharification and fermentation (SSF) at
      high solid loadings.
AB  - Phosphoric acid plus hydrogen peroxide (PHP) pretreatment was employed on wheat
      straw for ethanol conversion by simultaneous saccharification and fermentation
      (SSF) at high loadings. Results showed solid loading of PHP-pretreated wheat
      straw can be greatly promoted to 20%. Although more enzyme input improved ethanol
      conversion significantly, it still can be potentially reduced to 10-20 mg
      protein/g cellulose. Increasing yeast input also promoted ethanol conversion,
      however, the responses were not significant. Response surface method was employed
      to optimize SSF conditions with the strategy of maximizing ethanol conversion and
      concentration and minimizing enzyme and yeast input. Results indicated that
      ethanol conversion of 88.2% and concentration of 69.9 g/L were obtained after 120
      h SSF at solid loading of 15.3%, and CTec2 enzyme and yeast were in lower input
      of 13.2 mg protein/g cellulose and 1.0 g/L, respectively. Consequently, 15.5 g
      ethanol was harvested from 100 g wheat straw in the optimal conditions.

PMID- 30096644
TI  - Synergetic effects during co-pyrolysis of biomass and waste tire: A study on
      product distribution and reaction kinetics.
AB  - The synergetic effects during co-pyrolysis of biomass and waste tire (WT) were
      investigated concerning the product distribution and reaction kinetics. Two
      biomass feedstocks were separately mixed with WT at different effective
      hydrogen/carbon ratio (H/Ceff), and analytical co-pyrolysis of mixtures was
      conducted using pyrolysis gas chromatography/mass spectroscopy at 500  degrees C.
      Product distributions were similar between different biomass feedstocks but
      varied significantly at different H/Ceff values. The percentage of hydrocarbons
      increased significantly when increasing H/Ceff, and the optimal H/Ceff was
      determined considering the correspondingly higher yield of polycyclic aromatic
      hydrocarbons and char residuals at higher percentage of WT. The experimental
      derivative thermogravimetric curves of mixtures at the optimal H/Ceff were
      compared with the calculated results based on kinetic analysis of three
      individual components using the distributed activation energy model. Significant
      synergetic effects were observed at the initial and final stages of the pyrolysis
      process.

PMID- 30096645
TI  - Mesophilic anaerobic co-digestion of residual sludge with different
      lignocellulosic wastes in the batch digester.
AB  - Co-digestion of residual sludge (RS) and different lignocellulosic wastes (LWs)
      including greening waste (GW), decocted Chinese herbs waste (DCHW) and sugarcane
      bagasse waste (SCBW) was investigated in batch digester. Results show that the
      application of GW presented the highest specific methane yield (161 mL CH4/g
      VSadded) due to its high carbohydrate fraction and more balanced C/N ratio in co
      substrate mixture. Buswell equation was applied and it is found that
      biodegradability index (BI) for co-digestion varied from 68.1% to 74.2% (53.0%
      for RS mono-digestion) depending on the lignin fractions of the LWs. Variation of
      pH, VFAs, alkalinity and ammonia throughout the digestion were also examined. The
      addition of LWs induced VFAs formation, as well as their conversion to methane.
      The higher microbial diversity in RS/LWs co-digestion further confirmed the
      positive effect of LWs addition in co-digestion.

PMID- 30096646
TI  - Development and validation of a rapid ultra-high performance liquid
      chromatography diode array detector method for Verbena officinalis L.
AB  - This study presents a fast and validated ultra-high performance liquid
      chromatography diode array detector (UHPLC-DAD) method for the simultaneous
      determination of the major compounds in Verbena officinalis L. (Verbenaceae), a
      medicinal plant listed in the European, British, and, Chinese Pharmacopoeias. In
      order to get reference substances, nine compounds, belonging to iridoids,
      flavonoids, and phenylpropanoid glycosides, were isolated from the herb extract.
      Two of them, namely cistanoside D and leucosceptoside A, were found in this plant
      species for the first time. Chromatographic separation was achieved in less than
      7 min on a Kinetex  1.7 u XB-C18 (50 * 2.10 mm) column by using a solvent
      gradient of water-acetonitrile modified with 0.1% formic acid. Method validation
      confirmed the assays sensitivity, linearity (R2 >= 0.997), precision (intraday
      precision <= 1.71%; interday precision <= 1.46%) and accuracy (recovery rates
      between 93.9% and 108.8%) for the quantitative analysis of the eight selected
      marker compounds. Identity and peak purity of the analytes was confirmed by
      coupling the UHPLC instrument to a quadrupole time-of-flight mass spectrometer
      via an electrospray ionization interface (ESI-QTOF-MS) operating in the negative
      ionization mode. Finally, the applicability of the developed UHPLC-DAD method was
      successfully proven for the sensitive quantitation of the major compounds in
      Verbena herb extracts, thereby providing a reliable tool for its rapid quality
      control.

PMID- 30096647
TI  - Metabolite profiling of "green" extracts of Corylus avellana leaves by 1H NMR
      spectroscopy and multivariate statistical analysis.
AB  - Corylus avellana L. (Betulaceae) leaves, consumed as infusion, are used in
      traditional medicine, for the treatment of hemorrhoids, varicose veins,
      phlebitis, and edema due to their astringent, vasoprotective, and antiedema
      properties. In previous works we reported from the leaves of Corylus avellana cv.
      "Tonda di Giffoni" diarylheptanoid derivatives, a class of plant secondary
      metabolites with a wide variety of bioactivities. With the aim to give an
      interesting and economically feasible opportunity to C. avellana leaves as source
      of functional ingredients for pharmaceutical and cosmetic formulations, "green"
      extracts were prepared by employing "eco-friendly" extraction protocols as
      maceration, infusion and SLDE-Naviglio extraction. Metabolite profiles of the
      extracts were obtained by 1H NMR experiments and data were processed by
      multivariate statistical analysis to highlight differences in the extracts and to
      evidence the extracts with the highest concentrations of bioactive metabolites.
      Based on the NMR data, a total of 31 compounds were identified. The metabolite
      variation among the extracts was evaluated using Principle Component Analysis
      (PCA) and Partial Least Squares-Discriminant Analysis (PLS-DA). Furthermore, the
      total phenolic content of the extracts was measured by Folin-Ciocalteu
      colorimetric assay and the antioxidant activity of extracts was assayed by the
      spectrophotometric tests DPPH* and ABTS and by an in vitro test based on the
      evaluation of cellular reactive oxygen species production stimulated by
      pyocyanin.

PMID- 30096648
TI  - Quantitative analysis of a pharmaceutical formulation: Performance comparison of
      different handheld near-infrared spectrometers.
AB  - Notwithstanding the first developments of miniaturized vibrational spectrometers
      more than a decade ago, only recently real handheld near-infrared (NIR)
      spectrometers (<200 g) became commercially available at significantly reduced
      costs compared to other portable systems. While on the one hand this development
      was driven by the consumer request for every-day-life applications by non
      experts, on the manufacturer side it was supported by the availability and
      potential of new technologies such as micro-electromechanical systems (MEMS). In
      the present communication calibration spectra of a solid pharmaceutical
      formulation consisting of two excipients and three active ingredients,
      acetylsalicylic acid (ASA), ascorbic acid (ASC) and caffeine (CAF), have been
      measured with four handheld NIR spectrometers based on different monochromator
      principles and have subsequently been used to develop partial least squares (PLS)
      models for the quantitative determination of the active ingredients. Taking into
      account the instrumental and spectral peculiarities of the four instruments and
      the three analytes, respectively, the detailed analysis of the calibration
      parameters and the prediction accuracy for a test sample set then allowed to
      compare the performance of the different spectrometers for the analytical problem
      under investigation.

PMID- 30096649
TI  - Discovery of a potent non-oxime reactivator of nerve agent inhibited human
      acetylcholinesterase.
AB  - Organophosphorous (OP) compounds (such as nerve agents) inhibit the enzyme
      acetylcholinesterase (AChE) by covalent phosphylation of a key serine residue in
      the active site of the enzyme resulting in severe symptoms and ultimately death.
      OP intoxications are currently treated by administration of certain oxime
      compounds. The presently fielded oximes reactivate OP-inhibited AChE by
      liberating the phosphylated serine. Recent research towards new reactivators was
      predominantly devoted to design, synthesis and evaluation of new oxime-based
      compounds dedicated to overcoming some of the major limitations such as their
      intrinsic toxicity, their permanent charge which thwarts penetration of brain
      tissues and their inability to effectively reactivate all types of nerve agent
      inhibited AChEs. However, in over six decades of research only limited success
      has been achieved, indicating that there is a need for alternative classes of
      compounds that could reactivate OP-inhibited AChE. Recently, a number of non
      oxime compounds was discovered in which the 4-amino-2
      ((diethylamino)methyl)phenol (ADOC) motif proved to be able to reactivate OP
      inhibited AChE to some extent. In this paper several structural derivatives of
      ADOC were synthesized and screened for their ability to reactivate human AChE
      (hAChE) inhibited by the nerve agents VX, sarin, tabun, cyclosarin and paraoxon.
      We here disclose that one of those compounds showed a remarkable ability to
      reactivate OP-inhibited hAChE in vitro and that it is the most potent non-oxime
      reported to date.

PMID- 30096650
TI  - Donepezil-butylated hydroxytoluene (BHT) hybrids as Anti-Alzheimer's disease
      agents with cholinergic, antioxidant, and neuroprotective properties.
AB  - The multifactorial nature of Alzheimer's disease (AD) calls for the development
      of multitarget agents addressing key pathogenic processes. A novel family of
      donepezil-butylated hydroxytoluene (BHT) hybrids were designed, synthesized and
      evaluated as multifunctional ligands against AD. The optimal compound 7d
      displayed a balanced multifunctional profile covering an intriguing
      acetylcholinesterase (AChE) inhibition (IC50, 0.075 MUM for eeAChE and 0.75 MUM
      for hAChE) and Monoamine oxidase B (MAO-B) inhibition (IC50, 7.4 MUM for hMAO-B),
      excellent antioxidant activity (71.7 MUM of IC50 by DPPH method, 0.82 and 1.62
      trolox equivalent by ABTS method and ORAC method respectively), and inhibitory
      effects on self-induced, hAChE-induced Abeta aggregation. Moreover, 7d possessed
      neuroprotective potency against H2O2-induced oxidative damage on PC12 cells and
      Lipopolysaccharides (LPS)-stimulated inflammation on BV2 cells. Compound 7d was
      capable of penetrating BBB and presented good liver microsomal metabolic
      stability. Importantly, compound 7d could dose-dependently reverse scopolamine
      induced memory deficit in mice without acute toxicity. Taken together, those
      outstanding results highlight the donepezil-BHT hybrid 7d as a promising
      prototype in the research of innovative compound for AD.

PMID- 30096651
TI  - Rational design of dimeric lipidated Xenopus glucagon-like peptide 1 analogues as
      long-acting antihyperglycaemic agents.
AB  - Dimerization is viewed as an effective means to enhance the binding affinity and
      therapeutic potency of peptides. Both dimerization and lipidation effectively
      prolong the half-life of peptides in vivo by increasing hydrodynamic size and
      facilitating physical interactions with serum albumin. Here, we report a novel
      method to discover long-acting glucagon-like peptide 1 (GLP-1) analogues by
      rational design based on Xenopus GLP-1 through a combined dimerization and
      lipidization strategy. On the basis of our previous structure analysis of Xenopus
      GLP-1, palmitic acid and a C-terminal Cys were firstly introduced into two
      Xenopus GLP-1 analogues (1 and 2), and the afforded 3 and 4 were further reacted
      with bis-maleimide amine to afford two dimeric lipidated Xenopus GLP-1 analogues
      (5 and 6). The in vitro and in vivo biological activities of 5 and 6 were
      significantly improved as compared with their monomers. Moreover, the selected
      compound 6 showed greater hypoglycemic and insulinotropic activities than
      liraglutide even when the dose of 6 was reduced to half in db/db mice.
      Pharmacokinetic test revealed that 6 had a ~ 3-fold longer half-life than
      liraglutide in Kunming mice and SD rats, and the longer half-life of 6 led to
      excellent long-acting hypoglycemic effects as confirmed by two different
      pharmacological methods conducted on db/db mice. Finally, a 7 weeks chronic study
      conducted on db/db mice demonstrated the better therapeutic efficacies of 6 on
      glucose tolerance normalization, HbA1c reduction and pancreas islets protection
      than liraglutide. The present research showed that combined dimerization and
      lipidization is effective when applied to Xenopus GLP-1 analogue to develop novel
      GLP-1 analogue for the treatment of type 2 diabetes. In addition, the promising
      preclinical data of 6 suggested the therapeutic potential of 6 as a novel anti
      diabetic agent.

PMID- 30096652
TI  - Rapid induction of apoptosis in tumor cells treated with a new platinum(II)
      complex based on amino-thiazolidinone.
AB  - Thiazolidinone derivatives have been previously shown significant anti-cancer
      activities. Two amino-thiazolidinone complexes, [Pt(HTone)Cl] (1) and
      [Cu(HTone)Cl] (3) (HTone = (Z)-2-((E)-(1-(pyridin-2
      yl)ethylidene)hydrazono)thiazolidin-4-one) and one ethyl-modified [Pt(ETone)Cl2]
      (2) (ETone = (Z)-3-ethyl-2-((E)-(1-(pyridin-2-yl)ethylidene)
      hydrazono)thiazolidin-4-one)], were designed and synthesized in order to explore
      novel metal-based antitumor agents. MTT assay indicated that 1 and 3 were
      markedly cytotoxic to MCF-7, HepG-2 and NCI-H460 tumor cells, superior to both
      cisplatin and the HTone ligand. Massive dead cells were observed as early as 6 h
      when treated with 1, indicating rapid action of 1 as compared to that of other
      compounds. More interestingly, Hoechst 33342 staining and flow cytometry analysis
      illustrated that only complex 1 could induce obvious cell apoptosis within 12 h,
      which was associated with the high-expression of Bax and cleavage of caspase-3
      from 35 kDa to 17 kDa. By means of ICP-MS assay, we found complex 1 could largely
      accumulate in tumor cells in a short time. Additionally, complex 1 showed no
      cross resistance against the cisplatin-resistant cells.

PMID- 30096653
TI  - Medicinal properties of terpenes found in Cannabis sativa and Humulus lupulus.
AB  - Cannabaceae plants Cannabis sativa L. and Humulus lupulus L. are rich in terpenes
      - both are typically comprised of terpenes as up to 3-5% of the dry-mass of the
      female inflorescence. Terpenes of cannabis and hops are typically simple mono-
      and sesquiterpenes derived from two and three isoprene units, respectively. Some
      terpenes are relatively well known for their potential in biomedicine and have
      been used in traditional medicine for centuries, while others are yet to be
      studied in detail. The current, comprehensive review presents terpenes found in
      cannabis and hops. Terpenes' medicinal properties are supported by numerous in
      vitro, animal and clinical trials and show anti-inflammatory, antioxidant,
      analgesic, anticonvulsive, antidepressant, anxiolytic, anticancer, antitumor,
      neuroprotective, anti-mutagenic, anti-allergic, antibiotic and anti-diabetic
      attributes, among others. Because of the very low toxicity, these terpenes are
      already widely used as food additives and in cosmetic products. Thus, they have
      been proven safe and well-tolerated.

PMID- 30096655
TI  - Exposure to drinking mediates the association between parental alcohol use and
      preteen alcohol use.
AB  - OBJECTIVE: The aim of the present study was to test the link between exposure to
      parental alcohol use (i.e., preteens seeing their parents drinking) and preteen's
      alcohol use. Specifically, this study aimed to (a) replicate the association
      between parental alcohol use and preteen alcohol use and (b) test whether alcohol
      use exposure mediated this association. METHOD: Families were recruited from five
      regions in the Netherlands from 104 schools that agreed to participate. Preteens
      (N = 755, Mage = 11.27, SD = 0.56, 45.8% boys) and their mothers (N = 755)
      participated in the study. Preteens reported lifetime alcohol use and parental
      alcohol use exposure. Mothers reported on alcohol use for both parents.
      Structural Equation Modelling was used to assess direct and mediated paths
      between parental alcohol use, preteen's exposure to alcohol use and preteen
      alcohol use in one model. RESULTS: Unexpectedly, father's alcohol use was
      negatively associated (beta = -0.121, p = .012) and mother's alcohol use was not
      associated (beta = 0.056, p = .215) with preteen's alcohol use. A positive
      indirect effect emerged through alcohol use exposure, showing that exposure to
      father's alcohol use mediated the association between parent's and preteen's
      alcohol use (beta = 0.064, p = .001). This effect was absent for mother's alcohol
      use (beta = 0.026, p = .264). Gender differences were non-significant.
      CONCLUSIONS: Parental alcohol exposure positively mediated the association of
      parental alcohol use with preteen's alcohol use. These effects were found for
      both boys and girls and were most robust for father's drinking. The findings
      might provide clues for preventive action, for example, by emphasizing that
      exposure should be restricted to prevent preteen's alcohol use.

PMID- 30096654
TI  - Synthesis and discovery of a drug candidate for treatment of idiopathic pulmonary
      fibrosis through inhibition of TGF-beta1 pathway.
AB  - In this study, anti-IPF lead compounds 42 and 44, derived from natural
      sesquiterpene lactones Isoalantolactone and alantolactone, were discovered by
      screening from a high-throughput TGF-beta1 reporter luciferase assay. Notably,
      they could reduce the myofibroblast activation and extracellular matrix
      deposition both in vitro and in vivo. Additionally, compounds 42 and 44 could
      significantly attenuate bleomycin-induced pulmonary fibrosis in mice. Further
      validation of pharmacokinetics study and toxicity evaluation indicated that
      compound 44 might be a promising anti-IPF drug candidate.

PMID- 30096657
TI  - Development and validation of a contextual behavioral distress intolerance task
      in cigarette smokers.
AB  - INTRODUCTION: Distress intolerance, an individual's perceived or actual inability
      to withstand negative emotional or physical distress, contributes to the
      maintenance of smoking. However, there is limited understanding of the contextual
      factors that impact distress intolerance in general or among smokers
      specifically. This study aimed to adapt and test a computerized behavioral
      persistence task that requires re-typing a passage while adhering to specific
      instructions (Contextual-Frustration Intolerance Typing Task [C-FiTT]). C-FiTT
      was designed to model contextual factors that influence distress intolerance,
      negative affect, and smoking urges. METHOD: Daily smokers (n = 550) were
      recruited through the use of Qualtrics Panels. Using a 2 * 2 + 1 experimental
      design, participants were randomly assigned to one of four C-FiTT conditions that
      crossed task difficulty (low or high difficulty) with passage content (neutral or
      tobacco withdrawal text), or a neutral control group. RESULTS: C-FiTT produced an
      average persistence time of 94.1 +/- 114.3 s and 64.7% of participants self
      terminated the task. C-FiTT also produced small to medium sized-increases in
      negative affect and smoking urges. Between-condition comparisons indicated that
      the high-difficulty C-FiTT produced shorter behavioral persistence, greater self
      termination likelihood, and larger increases in negative affect and smoking
      urges. The combination of high-difficulty and withdrawal content resulted in the
      shortest persistence time, 100% self-termination rate, and largest increases in
      negative affect and smoking urges, compared to other conditions CONCLUSIONS:
      Findings provide initial evidence for the validity of C-FiTT in smokers within
      the context of tobacco withdrawal at low and high levels of task difficulty.
      Avenues for refinement and use of C-FiTT are discussed.

PMID- 30096656
TI  - Method effects of the relation between family history of alcoholism and parent
      reports of offspring impulsive behavior.
AB  - There is an extensive, albeit inconsistent, literature on the relation between
      parental alcoholism and offspring impulsive behavior. The reasons for this
      inconsistency are likely multiple but it seems probable that method effects due
      to different methodological approaches might explain some of the inconsistencies.
      Offspring behavior is typically assessed based on informant reports. However, no
      specific method has been demonstrated as optimal for analyzing informant reports,
      and conclusions may differ depending on the method used. The present study
      compared findings derived from a multi-informant method proposed by Bauer et al.
      (2013) to other structural equation models. Participants came from Wave 7 of the
      Alcohol, Health and Behavior study and included mother and father reports of
      offspring impulsive behavior on the Health and Behavior Questionnaire (Armstrong,
      Goldstein, & the MacArthur Working Group on Outcome Assessment, 2003). There were
      368 offspring (50% female, age range 3-17 years, meanage = 6.78, SDage = 3.07)
      from 205 families. The multi-informant model and the single-reporter models each
      provided a good fit of the data; however, findings differed based on the approach
      employed. Specifically, the mother-only report model found that offspring with a
      family history of alcoholism (FHA) were more impulsive compared to offspring
      without a FHA; no effect of FHA was found in the other single-reporter models.
      Ratings of offspring impulsive behavior were higher on the father perspective
      factor suggesting alcoholic fathers were biased in their reports. These findings
      highlight the relation between FHA and impulsive behavior varies depending on the
      analytic method used.

PMID- 30096658
TI  - Synchronization criteria for inertial memristor-based neural networks with linear
      coupling.
AB  - This paper is concerned with the synchronization problem for an array of
      memristive neural networks with inertial term, linear coupling and time-varying
      delay. Since parameters in the connection weight matrices are state-dependent,
      that is to say, the connection weight matrices jump in certain intervals, the
      mathematical model of the coupled inertial memristive neural networks can be
      considered as an interval parametric uncertain system. Based on the interval
      parametric uncertainty theory, two different synchronization criteria for
      memristor-based neural networks are obtained by applying the p-matrix measure
      (p=1,2,infinity,omega), Halanay inequality and constructing suitable Lyapunov
      Krasovskii functionals. Two simulation examples with fully-connected and nearest
      neighboring topology are presented to demonstrate the efficiency of the obtained
      theoretical results.

PMID- 30096659
TI  - Characteristics of a suicide attempt predict who makes another attempt after
      hospital discharge: A decision-tree investigation.
AB  - The year following discharge from psychiatric hospitalization is a high-risk
      period for suicidal behavior, particularly among patients initially hospitalized
      after a suicide attempt. Demographic and clinical correlates have been
      identified; however, characteristics of the initial attempt may provide insight
      into risk for subsequent attempts as well. This investigation examined whether
      individual or a combination of suicide attempt characteristics predicted future
      attempts. Two hundred and eighteen psychiatric inpatients from the MacArthur
      Violence Risk Assessment Study with a recent suicide attempt were administered
      items from the Suicide Intent Scale and followed one year after discharge. Sixty
      nine (31.65%) made a subsequent attempt. Data were analyzed by a stepwise
      logistic regression, followed by an iterative receiver operator curve (IROC)
      analysis, a recursive partitioning classification tree. The cross-validated IROC,
      but not logistic regression, predicted subsequent suicide attempts. Furthermore,
      the IROC found that participants who made definite plans and underwent extensive
      preparation were at highest risk for subsequent attempts. These findings suggest
      that suicide attempt characteristics preceding psychiatric hospitalization can
      help identify patients at elevated risk for another attempt post-discharge.

PMID- 30096660
TI  - How well does a wellbeing measure predict psychiatric 'caseness' as well as
      suicide risk and self-harm in adolescents?
AB  - Screening for psychiatric disorders may be hampered by traditional measures that
      increase participant burden and elicit negative responses via denial and social
      desirability biases. This study examined the utility of a wellbeing measure to
      identify psychopathology and suicide risk in adolescent participants. 1,579
      students from Sydney schools participated in a survey which assessed wellbeing
      using the Satisfaction With Life Scale (SWLS) as well as psychiatric disorders
      and suicide risk. Results showed that low scores on the SWLS discriminated
      adolescents who had experienced a psychiatric condition or suicidality from those
      not so assigned. Specifically, students with no psychiatric diagnosis yielded a
      mean SWLS score of 28.0 while for those assigned a diagnosis, mean scores ranged
      from 19.4-3.0 across the various psychiatric conditions. Students who reported
      any suicidal ideation yielded a mean SWLS score of 22.7, and those with a current
      suicidal plan yielded a mean score of 17.7. We derived SWLS cut-off scores for
      predicting psychiatric caseness and suicidality but established that they had low
      positive predictive power. The SWLS therefore appears to provide a limited proxy
      measure of the chance of a psychiatric disorder or psychological distress, and
      might usefully complement more direct measures of such states.

PMID- 30096661
TI  - Prevalence of DSM-5 depressive disorders and comorbidity in Spanish early
      adolescents: Has there been an increase in the last 20 years?
AB  - The aim of the study was to investigate the current prevalence of DSM-5
      Depressive Disorders (DD) among Spanish school children and compare it with data
      obtained 20 years ago from the same place. We assessed comorbidity, severity and
      sociodemographic related factors. With a double-phase design, a sample of 1514
      students participated in the 1st phase and 562 students (175 at risk of
      depression) were assessed in the 2nd phase with the Mini-International
      Neuropsychiatric Interview for Kids. The estimated current prevalence of Major
      Depressive Disorder (MDD) was 1.6%, similar to the 1.5% found 20 years ago. A
      total of 3.4% were diagnosed with some form of DD (MDD or Persistent Depressive
      Disorder (PDD)). No significant differences between genders were found in either
      of the two periods studied. The rate of depressive symptoms (11.6%) was not
      significantly different from that of previous data (9.4%). 80% and 71.9% of the
      children diagnosed with MDD and PDD respectively also had an anxiety disorder. In
      conclusion, we have not found an increase in depression among Spanish early
      adolescents. However, the data on the prevalence of DD, the comorbidity, and the
      impairment all highlight the need to design and implement appropriate preventive
      interventions in schools.

PMID- 30096662
TI  - An initial investigation of nonsuicidal self-injury among male and female
      survivors of military sexual trauma.
AB  - Nonsuicidal self-injury (NSSI) has been understudied among survivors of military
      sexual trauma (MST). The aims of the current study were to: (1) describe
      characteristics of NSSI among survivors of MST and (2) determine if MST survivors
      who have engaged in NSSI differ from those who have never engaged in NSSI in
      terms of the severity of posttraumatic stress disorder (PTSD) and depressive
      symptoms, trauma-related cognitions, and recent suicidal ideation. Participants
      were 107 veterans (65 females, 42 males) with a history of MST who completed
      measures of NSSI, PTSD and depressive symptoms, recent suicidal ideation, and
      trauma-related cognitions. Approximately one-fourth of participants (n = 27;
      25.23%) endorsed a history of NSSI. The majority of participants who engaged in
      NSSI reported that they first engaged in NSSI following MST (n = 18; 66.67%). MST
      survivors with a history of NSSI reported more severe PTSD symptoms, recent
      suicidal ideation, and trauma-related cognitions. NSSI was relatively common in
      the sample and was associated with a more severe clinical presentation.
      Longitudinal research is needed to understand the development, maintenance, and
      function of NSSI in MST survivors, especially as it pertains to risk for suicidal
      self-directed violence.

PMID- 30096663
TI  - Visible light activity of BaFe1-xCuxO3-delta as photocatalyst for atrazine
      degradation.
AB  - Nanosized BaFe1-xCuxO3 powders were prepared using the Pechini method. To limit
      grain growth and agglomeration, the temperature of calcination was limited to 800
      degrees C. For all samples, the cubic form of BaFeO2.75 was predominant with
      minor additional phases. Cu doping was found to have a remarkable effect on the
      structural cubic unit cell parameter as the Cu concentration increased. As shown
      by XRD,the samples were in the nanometer size range (17-63 nm). However, as the
      Cu concentration increases, the agglomeration increases with the highest surface
      area for the BaFe0.95Cu0.05O3 composition, which also displays the highest
      photocatalytic atrazine degradation. For this sample, more than 90% degradation
      of atrazine was obtained at the optimum conditions (120 min irradiation under
      visible light at pH 11 using 0.75 mg of the catalyst). The Atrazine degradation
      was found to follow the pseudo-order kinetics. GC/MS was used to detect the
      intermediates and the reaction pathways. All the prepared samples and produced
      waters at the end of the experiment were found to be nontoxic.

PMID- 30096664
TI  - Biodegradation of anionic surfactants by Alcaligenes faecalis, Enterobacter
      cloacae and Serratia marcescens strains isolated from industrial wastewater.
AB  - Pseudo-persistent organic pollutants, such as anionic surfactants (AS), are
      nowadays among the more complex problems that threaten the aquatic environments
      and other environmental compartments. The present work describes the
      identification and efficiency of a consortium, isolated from Algerian industrial
      wastewater, to remove three anionic surfactants (i.e., sodium
      dodecylbenzenesulfonate (SDBS), sodium dodecyl sulfate (SDS) and sodium lauryl
      ether sulfate (SLES)). The genetic analysis of 16S rRNA indicated that these
      strains are Alcaligenes faecalis, Enterobacter cloacae and Serratia marcescens.
      Under aerobic conditions, pH 7.0 and optimum temperature of 30  degrees C, the
      mixed consortium allowed to degrade 85.1% of initial SDBS amount after 144 h of
      incubation with half-life of 20.8 h. While E. cloacae and S. marcescens pure
      strains eliminated 46% and 41% less SDBS respectively. Evenly, SDS was degraded
      at only 23.71% by A. faecalis strain. However, the degradation capacity of SDS by
      the consortium was very high (94.2%) with a half-life of 9.8 h. The SLES anionic
      surfactant showed a lower biodegradation by the consortium (47.53%) due to the
      presence of ether oxide units in the chemical structure of SLES which induced
      toxicity to the medium. The investigation of the biodegradation of this type of
      organic pollutants by microorganisms has recently become a key issue for the
      environmental protection area.

PMID- 30096665
TI  - The effects of emamectin benzoate or ivermectin spiked sediment on juvenile
      American lobsters (Homarus americanus).
AB  - This study examined the effects of a range of 1/2-log concentrations of emamectin
      benzoate (commercially applied as SLICE(r)) and ivermectin (commercially applied
      as IVOMEC(r)) on juvenile American lobster, Homarus americanus. Phase I of the
      research assessed acute (up to 4 days) and chronic (30-day) toxicity of sediment
      dosed with the active ingredients emamectin benzoate (EMB) formulated as SLICE(r)
      or ivermectin (IVM) formulated as IVOMEC(r) at various nominal concentrations
      (EMB: 15, 48, 150, 475 and 1500 ng g-1 wet sediment; IVM: 3, 9.5, 30, 95 and 300
      ng g-1 wet sediment) on juvenile Atlantic lobster (stages IV). Phase II evaluated
      sublethal effects (e.g., growth, moulting success) of all lobster surviving past
      the 30 day exposure period, over an additional 41 days. Chemical analysis of EMB
      and IVM in sediment samples from the exposure tanks revealed a strong linear
      association (R2 values 0.99 and 0.98 for EMB and IVM, respectively) between
      nominal dose and measured concentration of compound. EMB exposure concentrations
      at very high levels (>= 343.3 ng g-1) were acutely toxic to juvenile lobster such
      that 100% of lobsters had died after 13 days of exposure. The maximum cumulative
      mortality of lobsters exposed to the highest concentrations of EMB and IVM was
      100% after 10 days and 25 days, respectively. The 10-day LC50 estimates (+/- 95%
      CI) for EMB and IVM were 250.23 +/- 90.4 and 212.14 +/- 202.64 ng g-1,
      respectively. Using abnormal behaviour as an indicator, the 15-day EC50 estimates
      (+/- 95% CI) for EMB and IVM were 96.19 +/- 51.42 and 15.82 +/- 6.93 ng g-1,
      respectively. The NOEC (no observed effect concentration) for abnormal behaviour
      was 0.0 ng g-1 for each product and the LOEC (lowest observed effect
      concentration) was 8.8 and > 3.0 ng g-1 for EMB and IVM, respectively.
      Observations on sublethal effects included delayed moulting to stage VI and
      reduced growth at higher exposure concentrations for both therapeutants. Using
      failure to moult to stage V or VI as an indicator, the 15-day EC50 estimates (+/-
      95% CI) for EMB and IVM were 32.72 +/- 18.26 and 14.00 +/- 12.43 ng g-1,
      respectively. The NOEC for failure to moult to stage V only was 343.3 and 14.7 ng
      g-1 for EMB and IVM, respectively. Whereas, the LOEC was 1066.7 and > 61.0 ng g-1
      for EMB and IVM, respectively. The concentrations of EMB and IVM tested in the
      present study were acutely toxic to juvenile lobster exposed to the highest
      dosages (343.3 and 1066.7 ng EMB g-1 and 61.0 and 300.0 ng IVM g-1). There was
      significant evidence of chronic toxicity, longer exposure increased mortality
      with LT50 values decreasing with increasing test material concentration.

PMID- 30096666
TI  - Effects of waterborne exposure to the antidepressant fluoxetine on swimming,
      shoaling and anxiety behaviours of the mosquitofish Gambusia holbrooki.
AB  - Chemical pollution from pharmaceuticals is increasingly recognized as a major
      hazard to the aquatic biota. Among the wide variety of pharmaceuticals,
      fluoxetine (FLX) is one of the most widely prescribed antidepressants, and
      therefore, it is frequently identified in the aquatic environment. As FLX is
      designed to alter human behaviour and many physiological pathways are conserved
      across vertebrates, this drug may affect the behaviour of fish living in FLX
      polluted environments. Here, we exposed groups of female mosquitofish Gambusia
      holbrooki to waterborne FLX for 14 days, under semi-static conditions with daily
      renewal of test solutions. Following exposure, we conducted a set of behavioural
      assays in individual fish, aimed at assessing the effects of FLX on their
      locomotor activity and behavioural responses. We found that FLX impaired swimming
      behaviour at high concentrations (25 MUg/L and 50 MUg/L) but not at low
      concentrations close to environmental levels (1 MUg/L and 5 MUg/L). When swimming
      activity was assessed 5 min after transfer of the focal fish to the testing tank,
      50 MUg/L FLX was the only concentration showing significant effects. However,
      when the same trials were performed 24 h later, 25 MUg/L FLX turned out to be an
      effect concentration in addition to 50 MUg/L. Interestingly, these concentrations
      would elicit fish plasma concentrations comprised within the range of human
      therapeutic doses. When subjected to a light/dark preference test, fish showed
      tendency to remain less time in the dark area at high FLX concentrations, thus
      suggesting an anti-anxiety response. Shoaling behaviour was not affected by FLX
      exposure. Our study contributes to the growing body of literature evaluating the
      effects of FLX on animal behaviour. Regarding the experimental design used in
      behavioural testing, our findings suggest that focal fish should be subjected to
      long habituation periods, namely of at least a few hours, in order to better
      assess the effects of drug exposure.

PMID- 30096667
TI  - Acesulfame potassium: Its ecotoxicity measured through oxidative stress
      biomarkers in common carp (Cyprinus carpio).
AB  - Acesulfame potassium (ACS) is a widely-used sweetener worldwide. Its presence has
      been demonstrated in diverse bodies of water. However, the deleterious effects
      this causes in aquatic organisms has not yet been identified, which generates
      controversy concerning the risks that ACS represents after its disposal into the
      bodies of water. Thus, the objective of this work was to evaluate if the exposure
      of ACS in environmentally-relevant concentrations was capable of producing
      oxidative stress in blood, liver, gill, brain and muscle of common carp (Cyprinus
      carpio). With this finality, the carp were exposed to two environmentally
      relevant concentrations (0.05 and 149 MUg L-1) at different exposure times (12,
      24, 48, 72 and 96 h), having controls in the same conditions for each exposure
      time. Posteriorly, the following biomarkers of damage were evaluated:
      hydroperoxide content (HPC), level of lipoperoxidation (LPX) and protein carbonyl
      content (PCC), as well as the activity of antioxidant enzymes superoxide
      dismutase (SOD) and catalase (CAT). The results showed that ACS produces
      significant increase in damage biomarkers evaluated in all organs, mainly in
      gill, brain and muscle, as well as significant changes in the activity of
      antioxidant enzymes in the same organs. Thus, it is concluded that ACS is capable
      of producing oxidative stress in common carp (Cyprinus carpio).

PMID- 30096669
TI  - Correlation of dengue incidence and rainfall occurrence using wavelet transform
      for Joao Pessoa city.
AB  - Dengue, a reemerging disease, is one of the most important viral diseases
      transmitted by mosquitoes. In this study, 55,680 cases of dengue between 2007 and
      2015 were reported in Paraiba State, among which, 30% were reported in Joao
      Pessoa city, with peaks in 2015, 2011 and 2013. Weather is considered to be a key
      factor in the temporal and spatial distribution of vector-transmitted diseases.
      Thus, the relationship between rainfall occurrence and dengue incidences reported
      from 2007 to 2015 in Joao Pessoa city, Paraiba State, Brazil, was analyzed by
      means of wavelet transform, when a frequency analysis of both rainfall and dengue
      incidence signals was performed. To determine the relationship between rainfall
      and the incidence of dengue cases, a sample cross correlation function was
      performed to identify lags in the rainfall and temperature variables that might
      be useful predictors of dengue incidence. The total rainfall within 90 days
      presented the most significant association with the number of dengue cases,
      whereas temperature was not found to be a useful predictor. The correlation
      between rainfall and the occurrence of dengue cases showed that the number of
      cases increased in the first few months after the rainy season. Wavelet analysis
      showed that in addition to the annual frequency presented in both time series,
      the dengue time series also presented the 3-year frequency from 2010. Cross
      wavelet analysis revealed that such an annual frequency of both time series was
      in phase; however, after 2010, it was also possible to observe 45 degrees  up
      phase arrows, which indicated that rainfall in the present year led to an
      increased dengue incidence the following year. Thus, this approach to analyze
      surveillance data might be useful for developing public health policies for
      dengue prevention and control.

PMID- 30096668
TI  - Recycled desalination membranes as a support material for biofilm development: A
      new approach for microcystin removal during water treatment.
AB  - Increased harmful cyanobacterial blooms and drought are some negative impacts of
      global warming. To deal with cyanotoxin release during water treatment, and to
      manage the massive quantities of end-of-life membrane waste generated by
      desalination processes, we propose an innovative biological system developed from
      recycled reverse osmosis (RO) membranes to remove microcystins (MC). Our system,
      named the Recycled-Membrane Biofilm Reactor (R-MBfR), effectively removes
      microcystins, while reducing the pollution impact of RO membrane waste by
      prolonging their life span at the same time. This multidisciplinary work showed
      that the inherent flaw of RO membranes, i.e., fouling, can be considered an
      advantageous characteristic for biofilm attachment. Factors such as roughness,
      hydrophilic surfaces, and the role of calcium in cell-cell and cell-surface
      interactions, encouraged bacterial growth on discarded membranes. Biofilm
      development was stimulated by using a laboratory-scale membrane module simulator
      cell. The R-MBfR proved versatile and was capable of degrading 2 mg.L-1 of MC in
      24 h. The economic feasibility of the scaling-up of the hypothetical R-MBfR was
      also validated. Therefore, this membrane recycling could be a future green cost
      effective alternative technology for MC removal.

PMID- 30096670
TI  - Effective one-step saccharification of lignocellulosic biomass using magnetite
      biocatalysts containing saccharifying enzymes.
AB  - Lignocellulosic biomass, packed with sugars, is one of the most available
      renewable resources for biofuels and bioproducts production. To release the
      sugars for the production, enzymatic hydrolysis (saccharification) of pretreated
      lignocellulosic biomass are required. However, the saccharification process is
      costly, inefficient, and requires multi-step operations. This is in part due to
      the high cost and the limited selection of commercial enzymes which commonly have
      different optimal pH and temperatures. Here we reported a one-step
      saccharification of pretreated lignocellulosic biomass using immobilized
      biocatalysts containing five different saccharifying enzymes (SEs) with a similar
      optimum pH and temperature. The five SEs - endo-1,4-beta-d-glucanase (an
      endoglucanase, eglS), cellobiohydrolase (an exoglucanase, cbhA), and beta
      glucosidase (bglH), endo-1,4-beta-xylanase (an endoxylanase, xynC) and beta
      xylosidase (bxlB) - were successfully expressed and produced by E. coli BL21.
      Better saccharification of pretreated corn husks was observed when using the five
      crude SE enzymes than those using two commonly used SEs, endo-1,4-beta-d
      glucanase and beta-glucosidase. The five SEs were cross-linked in the absence or
      the presence of magnetic nanoparticles (hereafter referred as SE-CLEAs and M-SE
      CLEAs, respectively). By using SE-CLEAs, the highest amount of reduced sugar (250
      mg/g biomass) was measured. The activity of immobilized SEs is better than free
      crude SEs. The M-SE-CLEAs can be reused at least 3 times for effective
      saccharification of pretreated lignocellulosic biomass.

PMID- 30096671
TI  - An integrated approach for investigating the correlation between floods and river
      morphology: A case study of the Saalach River, Germany.
AB  - Man-made structures in the Saalach River have changed the hydromorphological
      characteristics of the river regime. In some river reaches, the Saalach has lost
      the high morphological versatility and high variation in sediment transport
      characteristic of a mountain river. Among the negative effects, an extreme flow
      discharge in combination with riverbed variation could be one of the possible
      causes of flood disasters along the river. For example, the heavy and long
      lasting rainfall in June 2013 led to a peak discharge of 1100 m3/s, which was
      slightly above the 100-year flood return period, inundating a nearby city.
      However, the influence of the man-made structures on this flood event in this
      reach is unclear. In this study an integrative hydromorphological model is
      applied to evaluate this impact by a comparison with a standard clear water model
      with fixed bed. Moreover, a comparative analysis of a three-and two-dimensional
      flow model is performed to assess the models suitability representing the flow in
      this river stretch. The integrative model concept is based on the software
      TELEMAC-MASCARET, in an enhanced version for better representing graded sediment
      transport in rivers. In contrast to our integrative model, the standard clear
      water model with fixed bed overestimates the water elevations as it cannot take
      the significant changes in morphology into account. Results demonstrate that our
      proposed model more accurately represents the inundation in the floodplain and
      could thus be used to provide more reliable predictions to decision-makers for
      improved flood protection strategy.

PMID- 30096672
TI  - Variation of water use efficiency across seasons and years: Different role of
      herbaceous plants in desert ecosystem.
AB  - Desert ecosystems often structured in two distinct layers of woody and herbaceous
      plants. Changes in community composition alter the fractional coverage by bare
      soil, woody and herbaceous plants, with potential effects on water and carbon
      fluxes. We used eddy covariance measurements and chamber method in two similar
      shrub-dominated desert communities (Tamarix community and Haloxylon community) to
      assess inter- and intra-annual variations of ecosystem water use efficiency
      (EWUE) (where we distinguished whole ecosystem EWUE as EWUEE, and EWUE of shrub
      and herbaceous layers as EWUEShrub and EWUEHerb) in central Asia. In the Tamarix
      community, 11 years of carbon and water fluxes showed that years with larger
      herbaceous cover (referred to as shrub-herb years) had significant higher EWUEE
      than years with lower herbaceous cover (referred to as shrub years), with the
      values of 1.07 +/- 0.11 vs. 0.68 +/- 0.03 g C/kg H2O. There was a significant
      positive correlation between EWUEE and the maximum herbaceous plants cover. In
      the Haloxylon community, chamber measurements during a shrub year demonstrated
      that the shrub layer contributed most to the gross ecosystem productivity (GEP)
      and evapotranspiration (ET) of the system, with the herbaceous layer contributing
      around 30% at the beginning of the growing season, and decreasing to nearly zero
      during the middle and at the end of the growing season. The shrub layer EWUEShrub
      was significant higher than that in the herbaceous layer (EWUEHerb) throughout
      the growing season (1.82 +/- 0.11 vs. 1.06 +/- 0.32 g C/kg H2O). EWUEShrub was
      positively correlated with EWUEE, but there was no relationship between EWUEHerb
      and EWUEE in a shrub year. This study shows that the variability of the
      herbaceous layer across seasons and years in these desert ecosystems is crucial
      for predicting water and carbon cycling under ongoing and projected climatic
      change scenarios in shrub-dominated desert ecosystems.

PMID- 30096673
TI  - Impacts of potential HONO sources on the concentrations of oxidants and secondary
      organic aerosols in the Beijing-Tianjin-Hebei region of China.
AB  - We first coupled indoor emissions and biomass burning emissions into the WRF-Chem
      model besides the other four potential HONO sources (i.e., traffic emissions,
      soil emissions, and heterogeneous reactions on aerosol and ground surfaces).
      Eight simulations were performed in the Beijing-Tianjin-Hebei region (BTH) of
      China in August of 2006. The results indicated that traffic emissions and
      heterogeneous reactions on ground and aerosol surfaces were the key sources of
      HONO at night, accounting for ~41%, ~27% and ~20% of the nighttime simulated HONO
      concentrations, respectively. The two heterogeneous reactions were the main
      contributors during the day, accounting for ~66% (ground surfaces) and ~19%
      (aerosol surfaces) of the daytime simulated HONO concentrations. The indoor
      emission source could be the second largest contributor during nighttime and led
      to a maximum hourly enhancement of 0.59 and 0.76 ppb at the central urban sites
      of Beijing and Tianjin, respectively. The six potential HONO sources enhanced the
      monthly meridional-mean concentrations of O3, OH and HO2 by 5-44%, 5~>150% and
      5~>200%, respectively, leading to an enhancement of 1-3 MUg m-3 in the monthly
      averaged concentrations of secondary organic aerosol (SOA), and that of 10-35 MUg
      m-3 in the largest hourly concentrations of SOA within 1000 m above the ground in
      the BTH. The major precursors of the enhanced SOA were Xylenes, Toluene and
      BIGALK (lumped alkanes C > 3). The inclusion of the six potential HONO sources in
      the WRF-Chem model considerably improved the HONO simulations at both urban and
      suburban sites compared with the corresponding observations. The above results
      suggested that the six potential HONO sources significantly enhanced the
      atmospheric oxidation capacity and thus accelerated SOA chemical aging in the BTH
      of China, leading to large enhancements in the hourly SOA concentrations and
      aggravating haze events in this region.

PMID- 30096674
TI  - Effect of long-term manure slurry application on the occurrence of antibiotic
      resistance genes in arable purple soil (entisol).
AB  - The application of animal manure is a highly recommended traditional agricultural
      practice for soils of relatively low fertility. However, for the farmland purple
      soils that are widely distributed in the upper Yangtze River region, little
      knowledge has been established in previous studies about the changes in the
      antibiotic resistome upon manure amendment. In the present study, the impact of
      long-term pig manure slurry application on the occurrence of antibiotic
      resistance genes (ARGs) and bacterial community was assessed in arable calcareous
      purple soil using high-throughput quantitative polymerase chain reaction and
      Illumina sequencing. Four treatments, including a non-fertilization control (CK)
      and pig manure (OM), OM plus mineral N fertilizer (OMN) and OM plus mineral NPK
      fertilizer (OMNPK) treatments were investigated. Across all the soil samples
      receiving different treatments, a total of 139 unique ARGs and 6 mobile genetic
      element genes were detected, with multidrug and beta-lactam the two most dominant
      types of ARGs. The results of the principal coordinate analysis (PCoA) suggest
      that the profiles of soil ARGs in the two treatments of OM combined with mineral
      fertilizer(s) (i.e., OMN and OMNPK) were similar to those in the control
      treatment, while the soil receiving only pig manure application had a different
      pattern of ARGs from the soils in the other three treatments. A clear reduction
      of soil ARGs was observed in the OM treatment. Significant and positive
      relationships were found not only among ARGs but also between mobile genetic
      elements (MGEs) and ARGs. However, no significant relationships were detected
      between ARG patterns and bacterial community composition. These results imply
      that the long-term application of pig manure slurry to purple soil does not lead
      to the prevalence of ARGs; however, the potential for the horizontal transfer of
      ARGs in calcareous purple soil should not be ignored.

PMID- 30096675
TI  - Summertime high resolution variability of atmospheric formaldehyde and non
      methane volatile organic compounds in a rural background area.
AB  - On rural background areas atmospheric formaldehyde (HCHO) is important for its
      abundance and chemical reactivity, directly linked to the tropospheric ozone
      formation processes. HCHO is also toxic and carcinogenic to humans. Atmospheric
      HCHO was continuously measured in summer 2016 during 81 days (N = 6722, average:
      1.42 ppbv) in a rural background area in Northern Spain, Valderejo Natural Park
      (VNP) using a Hantzsch fluorimetric system. To better characterize the
      photochemical processes the database was completed with hourly measurements of 63
      Non-Methane Hydrocarbons (NMHC) performed by gas chromatography and other common
      atmospheric pollutants and meteorological parameters. HCHO mixing ratios were
      highly correlated with ozone and isoprene. Cloudy and rainy days, with low
      temperature and radiation, led to low HCHO mixing ratios, with maxima (<2 ppbv)
      registered around 14 UTC. On days with increased radiation and temperature HCHO
      maxima occurred slightly later (<6 ppbv, ~16:00 UTC). During clear summer days
      with high temperature and radiation, two HCHO peaks were registered daily, one
      synchronized with the radiation maximum (~3-4 ppbv, ~13:00 UTC) and an absolute
      maximum (<10 ppbv, ~18:00 UTC), associated with the addition of HCHO coming into
      VNP due to inbound transport of old polluted air masses. In the ozone episode
      studied, the processes of accumulation and recharge of ozone and of HCHO ran in
      parallel, leading to similar daily patterns of variation. Finally, HCHO mixing
      ratios measured in VNP were compared with other measurements at rural, forested,
      and remote sites all over the world, obtaining similar values.

PMID- 30096676
TI  - The impact of woodchip-gravel mixture on the efficiency and toxicity of
      denitrification bioreactors.
AB  - Woodchip-based denitrification bioreactors are widely used for treatment of high
      loads of nitrate pollution in agricultural run-off water. A concern raised
      recently, as a consequence of various organic fillings being experimented with,
      is whether the positive effect given by nitrate reduction could override the
      negative effects of such bioreactors, mainly caused by degradation of wood and
      the production of potentially harmful conditions for aquatic ecosystems. This
      paper presents the results of the experimental testing of two different filling
      materials: birch (BWCH) and spruce (SWCH) woodchip, and their mixture with washed
      gravel (WG) in volumetric ratio 10:1. We have focused on the leaching of organic
      carbon and phenols, and its impact on selected aquatic organisms, as well as on
      their denitrification efficiency and NO3- load removal rate (LRT). The results
      show that TOC, DOC and FNI (phenolic index) leaching is higher for the pure
      woodchip materials and is closely correlated with the growth inhibition of tested
      organisms (Vibrio fischeri, Daphnia magna, Desmodesmus subspicatus, Lemna minor).
      The highest denitrification efficiency and the highest load removal rates were
      recorded in mixed filling material (96% and 1.4 mg NO3-.dm3.d-1 for WG:BWCH; 85%
      and 1.2 mg NO3-.dm3.d-1 for WG:SWCH). Denitrification bioreactors with mixed
      woodchip filling material present a promising, cheap, and extensive technology
      for the treatment of agricultural field run-offs.

PMID- 30096677
TI  - Net ecosystem carbon and greenhouse gas budgets in fiber and cereal cropping
      systems.
AB  - To assess the contributions of fiber and cereal production on climate change, the
      net ecosystem exchange of carbon dioxide (CO2), main exchanges of non-CO2 carbon,
      and methane (CH4) and nitrous oxide (N2O) fluxes were continuously monitored
      throughout two year-round crop cycles (Y1 and Y2: 1st and 2nd year-round crop
      cycles, respectively) using eddy covariance, biometric observation, and static
      chamber methods in typical cotton and wheat-maize rotational cropping systems in
      China. The evaluation of net ecosystem carbon budgets (NECBs: considering net
      ecosystem CO2 exchange and non-CO2 carbon exchanges by fertilization, seeding,
      and harvest) and greenhouse gas budgets (GHGBs: adding CH4 and N2O fluxes to the
      NECBs based on CO2 equivalents) showed that the cotton cropping system
      persistently functioned as an intensive carbon (-1527 and -974 kg C ha-1 yr-1)
      and greenhouse gas (GHG) source (5618 and 3591 kg CO2-eq ha-1 yr-1) because of
      the large CO2 emissions during the long fallow periods (5748 and 5160 kg CO2 ha-1
      in Y1 and Y2, respectively). The wheat-maize cropping system had high net
      ecosystem production (NEP) and low harvest index and therefore, served as a
      notable carbon sink (1461 kg C ha-1 yr-1 in Y2). Although high irrigation water
      and chemical fertilizer inputs stimulated N2O emissions, the wheat-maize cropping
      system still behaved as an important GHG sink (-4257 kg CO2-eq ha-1 yr-1 in Y2)
      because of the tremendous net carbon sequestration. However, in Y1 incidental
      wind damage lowered the NEP and turned the wheat-maize cropping system into a GHG
      source (2144 kg CO2-eq ha-1 yr-1). The NEP, NECBs, and GHGBs of the double
      cropping system generally exceeded those of the single cropping system. The
      traditional rotation between double and single cropping systems should be
      restored to maintain soil carbon storage and alleviate the radiative forcing
      effects of cotton production.

PMID- 30096678
TI  - Assessment of fungi proliferation and diversity in cultural heritage: Reactions
      to UV-C treatment.
AB  - Fungi are present in natural and non-touristic caves due to the presence of
      organic matter provided mainly by insects or animals such as bats. In show caves,
      however, tourist infrastructure and the visitors themselves are an important
      source of organic matter. In addition, photosynthetic biofilms provide a high
      amount of carbon and nitrogen sources for fungi. This study was conducted to
      identify the fungal communities present in caves along with the potential use of
      UV-C treatment against their proliferation. Thus, fungal communities
      proliferating in biofilms in six French and Swiss show caves were analyzed using
      high throughput sequencing. The results show 385 species recorded, some of them
      previously described in cases of fungal outbreak. This preliminary study also
      aimed to test the use of UV-C light as an environmentally friendly method to
      treat fungal proliferation. Six fungal strains, from three different sources
      (Lascaux cave, La Glaciere cave, a church in Vicherey, France), were cultivated
      in an agar dish. Spores, mycelia and the entire colony were irradiated using
      several UV-C intensities. Results showed that four of the six fungi spores and
      mycelium died following a low-intensity UV-C treatment (2 kJ m-2, 160 s), though
      Ochroconis lascauxensis and Penicillium bilaiae spores showed higher resistance.
      Finally, it was demonstrated that the fungal colony could resist the UV-C light
      due to a shadow effect. The structure of the fungal colony was affected from the
      periphery to its inner part. However, after four 30 kJ m-2 treatments (39 min
      irradiation) all strains there definitively eradicated. Further studies will be
      necessary to examine the potential of UV-C light under cave conditions as a
      preventive and curative treatment.

PMID- 30096679
TI  - Bioreactor performance and microbial community analysis of autotrophic
      denitrification under micro-aerobic condition.
AB  - Autotrophic denitrification process is an effective strategy for treating sulfide
      and nitrate-enriched wastewater with low organic carbon. This study determined
      the sulfide oxidation and nitrate reduction rates and characterized the dominant
      bacteria and microbial community structure stimulated by micro-aerobic conditions
      in autotrophic denitrification system. With gradually increased sulfide
      concentration, the sulfide removal rate decreased to 37.8% at S2- = 600 mg/L,
      while the peak sulfide and nitrate removal rates (100% and 53.8%) were achieved
      at S2- = 800 mg/L with the air aeration rate of 20 mL/min. The Illumina
      sequencing results indicated that Thiobacillus accounted for 63% of total
      operational taxonomic units at generic level with sulfide concentration of 200
      mg/L under anaerobic condition. However, Azoarcus, Thauera and Aliidiomorina
      became the dominant genera under micro-aerobic condition and their abundance
      significantly and positively related to the sulfide concentration and aeration
      rate (p < 0.05). According to the 16S metaproteomics functional composition
      prediction, one potential mechanism for autotrophic denitrifying under micro
      aerobic condition was deduced that the oxidation of sulfide to thiosulfate
      further to sulfite was reinforced by trace oxygen, while the sulfite reductase
      activity was restrained. The decreased sulfide concentration weakened the
      toxicity inhibition on denitrifiers and accordingly the performance of
      autotrophic denitrification process was enhanced by micro-aerobic condition.

PMID- 30096680
TI  - Stormwater volume reduction and water quality improvement by bioretention:
      Potentials and challenges for water security in a subtropical catchment.
AB  - Climate change scenarios tend to intensify extreme rainfall events and drought in
      Brazil threatening urban water security. Low Impact Development (LID) practices
      are decentralized alternatives for flood mitigation and prevention. Recently,
      their potential has increasingly been studied in terms of stormwater harvesting.
      However, there is still a lack of knowledge about their potentialities in
      subtropical climate regions. Therefore, this study evaluated the behavior of a
      bioretention cell in a Brazilian city, during the dry period, which is critical
      in terms of pollutant accumulation and water availability. In addition to the
      runoff reduction and pollutant removal efficiency, this paper analyzed the
      potential for water reuse in terms of the stored volume and water quality
      guidelines. The results obtained show an average runoff retention efficiency of
      70%. Considering only the water availability aspects, the potential stored runoff
      could be reused for non-potable purposes, reducing the water demand in the
      catchment by at least half during the dry season. On the other hand, the
      bioretention presented two different conditions for pollutant removal: Condition
      A - the concentration values are within the recommended limits for water reuse.
      The parameters found in this condition were NO3, NO2, Zn, Mn, Cu, Cr; Condition B
      - the pollutant concentrations are above the guideline limits for water reuse and
      cannot be directly used for different purposes. The parameters found in this
      condition were Fe, Pb, Ni, Cd and color. Considering water reuse, an additional
      treatment is required for parameters in this second condition. Further studies
      should evaluate the design aspects that can allow collection of LIDs effluent,
      additional treatment if necessary, and reuse in the catchment.

PMID- 30096681
TI  - Distributions and pools of lead (Pb) in a terrestrial forest ecosystem with
      highly elevated atmospheric Pb deposition and ecological risks to insects.
AB  - There is growing interest in how heavy metals in remote ecosystems are elevated
      and affect environmental health. However, no studies have investigated
      atmospheric lead (Pb) deposition influences on the Pb bioaccumulation in insects
      in forests. Here we measure Pb concentrations and pools in forest vegetation,
      litterfall, organic soil, mineral soil, as well as litterfall deposition fluxes
      in a region severely affected by atmospheric deposition. We also analyzed Pb in
      insects which feed in the polluted forest vegetation and litter. Assessment of
      high Pb loads causing potential ecological risk to insects was also studied.
      Total Pb pool in the vegetation was 0.12 g m-2 and annual litterfall deposition
      flux of Pb was 13.42 mg m-2, which was much higher than those in the background
      areas. Pools of Pb from litter to mineral topsoil averaged 4.3 g m-2, which
      accounted for 97.3% of total pools (biomass + soil) in the forest ecosystem.
      Pools of Pb in surface soils were correlated significantly with the pools of
      total organic matter and elevation. Atmospheric deposition was inferred the major
      source of Pb in the forest ecosystem, which can be supported by the highest Pb
      concentrations in the moss and overstory foliage. The maximum Pb concentration
      was showed in the dung beetle (12.1 mg kg-1) residing in the soils compared that
      in the longicorn and of cicada, which would potentially pose negatively influence
      to predators along food chains.

PMID- 30096682
TI  - Decreasing longitudinal use of glucocorticosteroids in multiple sclerosis.

PMID- 30096683
TI  - Fake news, influencers and health-related professional participation on the Web:
      A pilot study on a social-network of people with Multiple Sclerosis.
AB  - BACKGROUND: Over the last few decades, patients have increasingly been searching
      for health information on the Internet. This aspect of information seeking is
      important, especially for people affected by chronic pathologies and require
      lifelong treatment and management. These people are usually very well informed
      about the disease but are nonetheless vulnerable to hopes of being cured or
      saved, often amplified by misinformation, myths, legends, and therapies that are
      not always scientifically proven. Many studies suggest that some individuals
      prefer to rely on the Internet as their main source of information, often
      hindering the patient-doctor relationship. A professional approach is imperative
      to maintain confidentiality, honesty, and trust in the medical profession.
      OBJECTIVE: we aimed to examine, in a medically supervised Italian web community
      (SMsocialnetwotk.com) dedicated to people with Multiple Sclerosis (pwMS), the
      posts shared by users and to verify the reliability of contents of posts shared
      by users pinpointed as Influencers through an online questionnaire. METHODS: we
      grouped the posts published on SMsocialnetwork from April to June 2015 into those
      with medical content (scientifically correct or fake news), and those related to
      social interactions. Later, we gave a questionnaire to the community asking to
      identify the three users/Influencers providing the most reliable advice for
      everyday life with MS and the three users/Influencers providing the most useful
      information about MS treatments. RESULTS: 308 posts reported scientific and
      relevant medical information, whereas 72 posts included pieces of fake news. 1420
      posts were of general interest. Four out of the 6 Influencers had written only
      posts with correct medical information (3 were pwMS, 1 was a Neurologist) and
      never any fake news. The remaining 2 appointed Influencers (2 pwMS) had written
      only posts about general interests. CONCLUSION: the identification of fake news
      and their authors has shown that the latter are never appointed as Influencers.
      SMsocialnetwork.com acted as a "web safe environment" where the Influencers
      contributed by sharing only correct medical information and never fake news. We
      speculate that the presence of neurologists and psychologists supervising the
      information flow might have contributed to reduce the risk of fake news spreading
      and to avoid their acquisition of authoritative meaning.

PMID- 30096684
TI  - Factors associated with perceived need for mental health care in multiple
      sclerosis.
AB  - BACKGROUND: Within the multiple sclerosis (MS) population, depression and anxiety
      are highly prevalent comorbidities that are associated with adverse outcomes such
      as diminished quality of life and disability progression. In the general
      population, many people who do not meet formal diagnostic criteria for depression
      or anxiety disorders still identify a need for mental health care. Limited data
      are available regarding the perceived need for mental health care among persons
      with MS. OBJECTIVE: We aimed to determine factors associated with a perceived
      need for mental health care in the MS population. METHODS: Participants with MS
      completed the Hospital Anxiety and Depression Scale (HADS) to assess severity of
      depression and anxiety symptoms, and reported whether they perceived a need for
      mental health care, in the context of a larger study examining the burden of
      psychiatric disorders in immune-mediated inflammatory disease. Participants were
      also evaluated using the Structured Clinical Interview for DSM-IV-TR (SCID) to
      diagnose depression or anxiety disorders. Participants reported their
      sociodemographic characteristics, and underwent physical assessments to determine
      their disability status. Descriptive analyses and binary logistic regression
      models were used to determine sociodemographic and clinical factors associated
      with perceived need for mental health care. RESULTS: Of 255 participants
      enrolled, 251 were included in this analysis. Most participants were women,
      Caucasian, with post-secondary education, with a mean (SD) age at enrollment of
      50.9 (12.9) years. They predominantly had a relapsing-remitting MS course. Nearly
      one-quarter of participants had a current SCID diagnosis of depression or anxiety
      (n = 57, 22.7%). Overall, 31.8% (n = 80) of participants reported a need for
      mental health care. These individuals were slightly younger at enrollment (p =
      0.037), but otherwise did not differ with respect to sociodemographic
      characteristics, compared to participants not reporting this need. Those
      identifying need for mental health care also had an earlier age of MS symptom
      onset (p = 0.011). After adjusting for sociodemographic and clinical factors,
      elevated symptoms of depression (odds ratio [OR] 2.36; 95%CI: 1.06, 5.25) and
      anxiety (OR 6.08; 95%CI: 2.78, 13.3) were associated with an increased likelihood
      of reporting a need for mental health care. Any current SCID diagnosis of
      depression or anxiety was not associated with perceived need for mental health
      care after accounting for symptoms of depression and anxiety. CONCLUSIONS: One
      third of people with MS identified a need for mental health care. Symptoms of
      anxiety and depression, but not current diagnosed mental health disorders, were
      the predominant factors associated with a perceived need for care.

PMID- 30096685
TI  - Physiological, micro-morphological and metabolomic analysis of grapevine (Vitis
      vinifera L.) leaf of plants under water stress.
AB  - Grapes are one of the most important fruits because of their economic and
      nutritional benefits, and grapevines are widely cultivated in arid and semi-arid
      areas. Therefore, it is critical to study the mechanism by which grapevines
      respond to water stress. In this research, micro-morphological and metabolomic
      analyses were conducted to evaluate the effects of water stress on stomatal
      morphology and volatile compounds extracted from the leaves of grapevine plants.
      There were two treatments: well-watered plants (watered daily) and drought
      stressed plants (no irrigation). Plant weights were recorded, and the well
      watered plants were irrigated daily to replace the water lost to
      evapotranspiration. The water status of the grapevines was determined according
      to their relative water content. The changes in proline content, hydrogen
      peroxide content, lipid peroxidation and antioxidant activities, as well as those
      of photosynthetic parameters and chlorophyll fluorescence, were monitored as
      markers of water stress. The microscopic changes in stomatal behavior were
      observed using a scanning electron microscope. A total of 12 secondary volatile
      compounds, including aldehydes, ketones and alcohols, were detected in the
      grapevine leaves. Among them, (E)-2-hexenal and 3-hexenal showed a significant
      increase after water stress. Multivariate statistical analysis revealed that the
      levels of 3-hexenal and (E)-2-hexenal were closely related to the changes in
      proline, hydrogen peroxide (H2O2), malondialdehyde (MDA), catalase (CAT) and
      superoxide dismutase (SOD). These results suggested that water stress could
      regulate the accumulation of green leaf volatiles, especially (E)-2-hexenal and 3
      hexenal, in coordination with the reactive oxygen species (ROS) scavenging
      system. These compounds may act as signaling compounds in response to water
      stress in grapevines.

PMID- 30096686
TI  - AmDREB2C, from Ammopiptanthus mongolicus, enhances abiotic stress tolerance and
      regulates fatty acid composition in transgenic Arabidopsis.
AB  - Dehydration-responsive element-binding (DREB) transcription factors (TFs) play a
      vital role in plant response to abiotic stresses. However, little is known about
      DREB TFs in plants adapted to harsh environments and in the formation of
      polyunsaturated fatty acids (PUFAs), a major membrane component closely
      associated with plant stress tolerance. Here, we characterized AmDREB2C in
      Ammopiptanthus mongolicus (Maxim. ex kom.) Cheng F., a desert evergreen broadleaf
      shrub with a high tolerance to harsh environments. AmDREB2C encodes a canonical
      DREB2-type TF, and the protein was localized in the nucleus. AmDREB2C had the
      highest expression levels in leaves of naturally growing shrubs in the wild
      during the winter season of a year of sampling. The expression was also induced
      by cold, heat and drought stresses in laboratory-cultured seedlings. Moreover,
      AmDREB2C was most abundantly expressed in young leaves and immature seeds rather
      than other tissues of the shrubs. Constitutive expression of AmDREB2C in
      Arabidopsis enhanced freezing, heat and drought tolerances of the transgenic
      plants, likely through inducing the expression of important stress-responsive
      genes. The transgene also increased the level of linolenic acid (C18:3), a major
      PUFA in most plant species, in leaves and seeds of the transgenic plants.
      Correspondingly, the transcription of FAD3, FAD7 and FAD8, three genes encoding
      fatty acid desaturases (FADs) responsible for the production of C18:3, showed a
      differential up-regulation in these two organs. This study provides new insight
      into the underlying molecular mechanisms of A. mongolicus' ability to endure
      harsh environments and DREB TF regulation of fatty acid desaturation.

PMID- 30096687
TI  - Significant chemical fluxes from natural terrestrial groundwater rival
      anthropogenic and fluvial input in a large-river deltaic estuary.
AB  - The shores of the Pearl River estuary are home to 35 million people. Their wastes
      are discharged into the large river delta-front estuary (LDE), one of the most
      highly polluted systems in the world. Here we construct a radium reactive
      transport model to estimate the terrestrial groundwater discharge (TGD) into the
      highly urbanized Pearl River LDE. We find the TGD comprises only approximately
      0.9% in term of water discharge compared to the river discharge. The TGD in the
      Pearl River LDE delivers significant chemical fluxes to the coast, which are
      comparable to the fluvial loadings from Pearl River and other world major rivers.
      Of particular importance is the flux of ammonium because of its considerable role
      in Pearl River estuary eutrophication and hypoxia. Unlike the ammonium in many
      other aquifers, the ammonium in the Pearl River aquifer system is natural and
      originated from organic matter remineralization by sulfate reduction in the
      extremely reducing environment. The TGD derived NH4+ is as much as 5% of the
      upstream Pearl River fluvial loading and 42% of the anthropogenic inputs. This
      high groundwater NH4+ flux may greatly intensify the eutrophication, shift the
      trophic states, and lead to alarming hypoxia within the affected ecosystems in
      the Pearl River LDE. The large TGD derived chemical fluxes will lead to
      deterioration of water and will potentially affect human health.

PMID- 30096688
TI  - Bioaugmented soil aquifer treatment for P-nitrophenol removal in wastewater
      unique for cold regions.
AB  - P-nitrophenol (PNP) is a toxic and recalcitrant organic pollutant and a usual
      intermediate in the production of fine chemicals, which has posed a significant
      threat to subsurface environment safety. Soil aquifer treatment (SAT) is a
      promising method to remove and remediate contamination in vadose zone with low
      cost and high efficiency. However, there are still research gaps for the
      treatment of recalcitrant contaminants by SAT in cold regions, such as un-robust
      indigenous microbes and low temperature constraint in vadose zone. The
      bioaugmentation technology was first introduced into SAT in order to enhance the
      removal ability of PNP by SAT operated in cold regions in this study. A high
      efficiency PNP-degrading bacterium was successfully isolated, which can
      efficiently degrade PNP below 200 mg L-1 with a degradation rate above 99% at 15 
      degrees C close to the real subsurface temperature in cold regions, and added
      into SAT for bioaugmentation. The feasibility of bioaugmented SAT and associated
      PNP removal process were investigated by laboratory sand columns, along with
      effects of the SAT operative parameters (namely PNP loading concentration, flow
      rate and soil saturation level of SAT). Within the range of PNP loading stresses
      tested (1-200 mg L-1), PNP removal efficiency was optimal at constant flow rate
      of 219 mL d-1 in unsaturated operating condition of SAT under 15  degrees C among
      all the investigated experimental conditions. Longer hydraulic residence time
      increased the PNP removal rate, although the accumulated mass removed reduced and
      the removal efficiencies remained constant in unsaturated operating condition of
      SAT. It is found from the comparison between the PNP removals via both
      unsaturated and saturated columns that slight difference only in the removal rate
      of PNP was observed and the highly efficient bioaugmented SAT can completely
      degrade PNP of 10 mg L-1 within 5 wetting/drying cycles under both scenarios.

PMID- 30096689
TI  - Water-quality impacts in semi-arid regions: can natural 'green filters' mitigate
      adverse effects on fish assemblages?
AB  - The effective aridity in riparian areas is increasing from climate change and
      from human water consumption, which exacerbates the impacts of effluents from
      wastewater-treatment plants and from catchment run-off in rivers. The potential
      of natural riparian areas to act as 'green filters' has long been recognized, but
      the possible ecological benefits of natural riparian areas over large-scale
      environmental gradients on fish have not been explored in detail. Using an
      extensive data-set from northeastern Spain (99,700 km2, 15 catchments, 530
      sites), ours is the first study to ask whether natural riparian vegetation can
      mitigate the effects of pollution on fish in rivers experiencing water scarcity.
      We used multimodel inference to explore the additive and interactive effects of
      riparian vegetation with nutrient pollution and water conductivity, which are
      among the world's worst river stressors, on multiple fish guilds, including
      widely distributed species and highly invasive alien fish species. Most models
      (54%) supported the additive effects of water-quality factors on fish, after
      having accounted for the influence of geography and hydrological alterations.
      Although many fewer models (7%) included riparian vegetation as an important
      predictor, riparian vegetation modulated the forms of the associations between
      fish and pollution. The relationship of nutrient pollution with native and alien
      fish richness changed from negative to positive with greater riparian structure
      or species richness. However, we found the opposite effect for the mean body size
      of sedentary fish, and only positive additive effects of riparian richness for
      the probability of occurrence of pelagic fish. Ammonium and nitrite
      concentrations adversely affected fish in these rivers up to 10 years after the
      enforcement of the implementation of the Water Framework Directive by the
      European Union. High conductivity also much affects fish, having negatives
      associations with migratory, pelagic, invertivorous and native fish, and positive
      associations with sedentary, benthic, omnivorous and alien fish. Therefore, the
      current status of natural riparian areas is unlikely to fully mitigate water
      quality impacts on fish. The conservation of freshwater resources in semi-arid
      regions, such as north-eastern Spain, requires improved waste-water treatments
      and better agriculture practices.

PMID- 30096690
TI  - Development of a mobile groundwater desalination system for communities in rural
      India.
AB  - The consumption of saline groundwater has contributed to a growing incidence of
      renal diseases, particularly in coastal communities of India. Although reverse
      osmosis (RO) is routinely used to remove salt from groundwater, conventional RO
      systems (i.e. centralized systems using spiral wound RO elements) have limited
      utility in these communities due to high capital and maintenances costs, and lack
      of infrastructure to distribute the water. Consequently, there is a need to
      develop an appropriate solution for groundwater treatment based on small-scale,
      mobile and community-led systems. In this work, we designed a mobile desalination
      system to provide a simple platform for water treatment and delivery of goods to
      rural communities. The system employs tubular RO membranes packed in a single,
      low-profile vessel which fits below the cargo space. The low-profile enables
      minimal intrusion on the space available for the transportation of goods.
      Pressure is delivered by a belt driven clutch pump, powered by the engine. Water
      is treated locally by connecting the intake to the village well while the vehicle
      idles. A combined numerical and experimental approach was used to optimise the
      module/system design, resulting in ~20% permeate flux enhancement. Experimental
      results revealed that the system can produce 16 L per square meter of membrane
      area per hour (LMH) at a salinity level of 80 ppm from a ~2000 ppm groundwater
      when it is feed at 1 m3/h at 8 bars. This indicates that a vehicle equipped with
      12 m2 of tubular RO membranes can deliver 1 m3 of drinkable water by using ~0.9 L
      of diesel. Assuming eight such systems could be implemented in a community to
      fulfil the water demands for a village with 2000 residents, a social business
      study revealed that a payback time of 2.5 years is achievable, even if the sale
      price of the water is relatively low, USD 0.18 (Rs 12, which is half of the
      lowest market price) per 20 L, including providing a goods transportation service
      at price of USD 5.25 (Rs 350) per 100 km.

PMID- 30096691
TI  - Impacts of shale gas production wastewater on disinfection byproduct formation:
      An investigation from a non-bromide perspective.
AB  - The rapid rise of shale gas development has triggered environmental and human
      health concerns due to its impacts on water resources, especially on disinfection
      byproduct (DBP) formation upon chlorination. Despite the recently reported
      results on bromide, the effects of non-bromide ions in production wastewater at
      extremely high levels are vaguely defined. In this study, we investigated the
      effects of production wastewater, with bromide and non-bromide species, on the
      formation of DBPs when production wastewater was spiked into surface waters at
      various percentages. Results showed that the introduction of debrominated
      production wastewater led to increased formation of some chlorinated DBP species
      in selected surface water and wastewater. As the spiking percentage of
      debrominated production wastewater increased, the chlorinated DBP species
      increased. The contributions of individual cations to DBP formation followed a
      sequence of magnesium > calcium > barium at 0.10% spiking percentage due to the
      different catalytic effects of their chelates with organic precursors. The study
      of anions suggested that the discharge of treated production wastewater
      containing elevated sulfate may further enhance DBP formation. The significance
      of this study lies in the fact that in addition to bromide concerns from
      production wastewater, non-bromide species also contributed to DBP formation. The
      gas production wastewater management decision should consider the negative
      impacts from both bromide and non-bromide species to better protect the receiving
      water resources.

PMID- 30096692
TI  - White and infrared light continuous photobioreactors for resource recovery from
      poultry processing wastewater - A comparison.
AB  - Concentrated wastewaters from agricultural industries represent a key opportunity
      for the upcycling of organics, nitrogen and phosphorus to higher value products
      such as microbial protein. Phototrophic or photosynthetic microbes very
      effectively capture input organics and nutrients as microbial protein. This study
      compares purple phototrophic bacteria (PPB) and microalgae (photosynthesis) for
      this purpose, treating real, high strength poultry processing wastewater in
      continuous photo bioreactors utilising infrared (IR) and white light (WL)
      respectively. Both reactors could effectively treat the wastewaters, and at
      similar loading rates (4 kgCOD m-3d-1). The infrared reactor (IRR) was irradiated
      at 18 W m-2 and the white light reactor (WLR) reactor at 1.5-2 times this. The
      IRR could remove up to 90% total chemical oxygen demand (TCOD), 90% total
      nitrogen (TN) and 45% total phosphorus (TP) at 1.0 d hydraulic retention time
      (HRT) and recover around 190 kg of crude protein per tonne of influent COD at 7.0
      kWh per dry tonne-1 light input, with PPB dominating all samples. In comparison,
      the WLR removed up to 98% COD, 94% TN and 44% TP at 43-90% higher irradiance
      compared to the PPB reactor. Microalgae did not dominate the WLR and the
      community was instead a mix of microbes (algae, bacteria, zooplankton and
      detritus - ALBAZOD) with a production of approximately 140 kg crude protein per
      tonne influent COD.

PMID- 30096693
TI  - Two analytical approaches quantifying the electron donating capacities of
      dissolved organic matter to monitor its oxidation during chlorination and
      ozonation.
AB  - Electron-donating activated aromatic moieties, including phenols, in dissolved
      organic matter (DOM) partially control its reactivity with the chemical oxidants
      ozone and chlorine. This comparative study introduces two sensitive analytical
      systems to directly and selectively quantify the electron-donating capacity (EDC)
      of DOM, which corresponds to the number of electrons transferred from activated
      aromatic moieties, including phenols, to the added chemical oxidant 2,2'-azino
      bis(3-ethylbenzothiazoline-6-sulphonate) radical cation (i.e., ABTS*+). The first
      system separates DOM by size exclusion chromatography (SEC) followed by a post
      column reaction with ABTS*+ and a spectrophotometric quantification of the
      reduction of ABTS*+ by DOM. The second system employs flow-injection analysis
      (FIA) coupled to electrochemical detection to quantify ABTS*+ reduction by DOM.
      Both systems have very low limits of quantification, allowing determination of
      EDC values of dilute DOM samples with <1 mg carbon per liter. When applied to
      ozonated and chlorinated model DOM isolates and real water samples, the two
      analytical systems showed that EDC values of the treated DOM decrease with
      increasing specific oxidant doses. The EDC decreases detected by the two systems
      were in overall good agreement except for one sample containing DOM with a very
      low EDC. The combination of EDC with UV-absorbance measurements gives further
      insights into the chemical reaction pathways of DOM with chemical oxidants such
      as ozone or chlorine. We propose the use of EDC in water treatment facilities as
      a readily measurable parameter to determine the content of electron-donating
      aromatic moieties in DOM and thereby its reactivity with added chemical oxidants.

PMID- 30096694
TI  - Reactive Photo-Fenton ceramic membranes: Synthesis, characterization and
      antifouling performance.
AB  - To develop reactive and antifouling membrane filtration systems, a photo-Fenton
      ceramic membrane was prepared by coating goethite (alpha-FeOOH) catalysts on a
      zirconia/titania alumina membrane via a cross-linking method. Scanning electron
      microscopy (SEM), X-ray diffraction spectroscopy (XRD) and Fourier transform
      infrared spectroscopy (FTIR) were used to characterize alpha-FeOOH catalysts and
      the surface coating quality. The cross linker yielded stable covalent binding
      between catalyst and membrane under room temperature and produced a homogeneous
      and smooth coating of catalyst on ceramic membranes. Photo-Fenton reactions were
      initiated with addition of H2O2 under UV irradiation to improve the foulant
      degradation on membrane surface while filtration. Membrane fouling was simulated
      by bovine serum albumin (BSA) and humic acid (HA). Our results show that the
      photo-Fenton reactions on the coated membranes slowed down the fouling kinetics
      and even reversed the fouling, leading to a stable transmembrane pressure (TMP)
      over time of filtration, as opposed to a monotonous increase of TMP due to
      surface fouling. The batch experiments verified that the photo-Fenton reactions
      achieved the degradation rates of 76% and 86% for HA and BSA respectively within
      60 min, with the mineralization rates of over 80% as indicated by the total
      organic carbon measurement. This study embarks on a novel antifouling membrane
      filtration process via incorporation of photo-Fenton reactions. The findings are
      also important for diverse applications of surface fouling mitigation and
      rationale design of fouling resistant surfaces or materials through photo-Fenton
      or other catalytic reactions.

PMID- 30096695
TI  - Electrochemical filtration process for simultaneous removal of refractory organic
      and particulate contaminants from wastewater effluents.
AB  - Versatile electrochemical reactions are effective for removing a wide range of
      water contaminants. This study focuses on the development and testing of
      bifunctional electrocatalytic filter anodes as reactive and separating media for
      the simultaneous removal of refractory dissolved organic and particulate
      contaminants from real wastewater effluents. The results show that the TiO2
      particle interlayers formed between the Ti fiber support and the top composite
      metal oxide catalyst layers assist in reducing filter pores to an effective size
      range that enables removal of most particulates within the wastewater. The double
      sheet design, which is a sandwich-structured module with an internal void space
      for permeate, prevents filter fouling, and transmembrane pressure can be
      maintained at a very low level of <5 kPa during batch and continuous flow reactor
      operations. Substantive and simultaneous removal of dissolved organics (e.g.,
      chromophores, fluorophores, 1,4-dioxane, chemical oxygen demand, and total
      organic carbon) and particulate matter (i.e., turbidity) are achieved, although
      removal rates and efficacies differ depending on the electric current density
      applied. Decolorization and particulate rejection occur swiftly and immediately,
      but 1,4-dioxane degradation is relatively slow and quite time-dependent. Possible
      1,4-dioxane degradation pathways during electrocatalysis are also proposed.
      Electrochemical filtration technology shows considerable promise for use in the
      next generation of advanced wastewater treatment solutions.

PMID- 30096697
TI  - Pyrazinium thioacetate capped gold nanoparticles as Fe(III) sensor and Fe(III)
      marked anti-proliferating agent in human neuroblastoma cells.
AB  - Gold nanoparticles (AuNPs) stabilized by new cationic 1-(3
      (acetylthio)propyl)pyrazin-1-ium ligand (PPTA) were synthesized. AuNPs stabilized
      by PPTA (PPTA-AuNPs) were found to be spherical and polydispersed with the
      average size of 60 nm. Human neuroblastoma (SHSY-5Y) cells permeability of PPTA
      AuNPs was found to be a key feature to study the intracellular quenching of
      Fe(III) proliferative activity. In vitro MTT assay revealed non-cytotoxicity of
      PPTA and PPTA-AuNPs at 100 MUM concentration, while treatment of 100 MUM of
      Fe(III) with SHSY-5Y cells resulted into higher cells viability. Contrary, a
      mixture of 1:1 Fe(III) with PPTA-AuNPs showed no change in the viability of cells
      at same concentration which suggests the intracellular complexation and
      recognition of Fe(III) by PPTA-AuNPs. AFM morphological analysis of SHSY-5Y cells
      also supported the MTT assay results, and it is safe to conclude that PPTA-AuNPs
      can be used as Fe(III) probes in living cells. In addition, Fe(III) caused a
      significant decrease in the absorbance of surface plasmon resonance (SPR) band of
      PPTA-AuNPs in a wide range of concentration and pH, with limit of detection 4.3
      MUM. Moreover, the specific response of PPTA-AuNPs towards Fe(III) was unaffected
      by the interference of other metals and components of real samples of tap water.

PMID- 30096696
TI  - Determination of interactions between human serum albumin and niraparib through
      multi-spectroscopic and computational methods.
AB  - The interactions between 2-{4-[(3S)-piperidin-3-yl] phenyl}-2H-indazole-7
      carboxamide (niraparib) and human serum albumin (HSA) were investigated through
      fluorescence and computational studies. Fluorescence experiments showed that the
      static quenching mechanism and the binding constant of the HSA-niraparib system
      at a single binding site was approximately 4 * 104 L mol-1. Thermodynamic
      constants indicated that the binding of niraparib to HSA was mainly driven by
      electrostatic interactions. Competition experiments and molecular docking
      simulations revealed that niraparib bound to site III of HSA. Synchronous
      fluorescence and Fourier transform infrared spectroscopy (FT-IR) results
      suggested that interactions between niraparib and HSA could affect the
      conformation and microenvironment of HSA. Circular dichroism (CD) measurements
      revealed that the alpha-helix contents of HSA negligibly increased after binding
      with niraparib. Molecular dynamics simulations demonstrated the stability of the
      binary HSA-niraparib system and confirmed that electrostatic forces accounted for
      the dominant contribution to system energy between HSA and niraparib.

PMID- 30096698
TI  - Prevalence and antifungal susceptibility profiles of Candida glabrata, Candida
      parapsilosis and their close-related species in oral candidiasis.
AB  - OBJECTIVE: To evaluate the importance of Candida glabrata, Candida parapsilosis
      and their close-related species, Candida bracarensis, Candida nivariensis,
      Candida metapsilosis and Candida orthopsilosis in patients with oral candidiasis
      and, to determine the in vitro activities of antifungal drugs currently used for
      the treatment. METHODS: One hundred fourteen isolates of C. glabrata and 97 of C.
      parapsilosis, previously identified by conventional mycological methods, were
      analysed by molecular techniques. In vitro antifungal susceptibility to
      fluconazole, itraconazole, miconazole, and nystatin was evaluated by CLSI M44-A2
      disk diffusion test, and by CLSI M27-A3 microdilution for fluconazole. RESULTS:
      All C. glabrata isolates were identified as C. glabrata sensu stricto, 93 out of
      97 C. parapsilosis isolates as C. parapsilosis sensu stricto, three as C.
      orthopsilosis and one as C. metapsilosis. Candida glabrata was mainly isolated in
      mixed cultures but C. parapsilosis complex was more frequent in pure culture.
      Candida metapsilosis and C. orthopsilosis were isolated as pure culture and both
      species were susceptible to all antifungal agents tested. Most C. glabrata
      isolates were susceptible to miconazole and nystatin, but resistant to
      fluconazole and itraconazole. Azole cross resistance was also observed. Candida
      parapsilosis isolates were susceptible to fluconazole although azole cross
      resistance to miconazole and itraconazole was observed. CONCLUSION: This study
      highlights the importance of accurate identification and antifungal
      susceptibility testing of oral Candida isolates in order to have an in-depth
      understanding of the role of C. glabrata and C. parapsilosis in oral candidiasis.

PMID- 30096699
TI  - Role of radiotherapy in improving activity of immune-modulating drugs in advanced
      renal cancer: Biological rationale and clinical evidences.
AB  - In the last few years, immune checkpoint inhibitors have been extensively
      investigated in renal cell carcinoma and led to remarkable results. Radiation
      therapy may increase the activity of immune modulating agents through different
      mechanisms, priming the immune system, recruiting immune cells to the tumor
      environment, and altering the immunosuppressive effects of the tumor
      microenvironment. Preclinical studies reported increased loco-regional control
      when radiation is combined with immune-checkpoint blockade. Moreover, increased
      systemic disease control has been demonstrated when local radiation is combined
      with both anti-CTLA-4 and anti-PD-1/PD-L1 inhibitors. Actually, several trials
      are ongoing testing the activity of radiation therapy in combination with
      different immune-modulating agents for the treatment of metastatic renal cell
      carcinoma. The aim of this paper is to focus on the biological rationale of
      adding radiation therapy to immune-modulating agents in renal cell carcinoma and
      to review the currently available clinical evidence about the combination of
      radiotherapy and immunotherapy.

PMID- 30096700
TI  - Postprandial gut hormone responses to Hass avocado meals and their association
      with visual analog scores in overweight adults: A randomized 3 * 3 crossover
      trial.
AB  - OBJECTIVE: To evaluate changes in postingestive gut hormone concentrations from
      the consumption of Hass avocado by addition or inclusion to lunch test meals, and
      to examine their association with measures of appetite sensation. METHODS: A
      randomized 3 * 3 crossover study was conducted with 26 healthy overweight adults.
      Participants consumed one of three test meals: avocado-free control (C);
      isoenergic avocado inclusive (AI); and, energy increased avocado added (AA) one
      week apart. Ghrelin, peptide YY3-36 (PYY3-36), gastric inhibitory peptide (GIP)
      and glucagon-like peptide-1 (GLP-1) concentrations were measured at specific
      times before and following the test meals. Appetite sensations (Hunger, Fullness,
      Satisfied, Desire, How Much) were self-assessed using a visual analog scale (VAS)
      tool at matching time points and a Composite VAS score was computed. Mixed models
      and repeated measures analysis were used to compare differences among the test
      meals for VAS measurements and gut hormones, and their associations were
      evaluated using regression analysis. RESULTS: A decrease in the 3-hour GLP-1 area
      under the curve (AUC) was observed in the AA meal compared to the C meal (P =
      0.03). Negative associations were found for PYY3-36 and GIP for Hunger, Desire
      and How Much, and positive associations for Fullness, Satisfied and the Composite
      VAS score (all P < 0.001). For GLP-1, a negative association for Hunger and a
      positive association for Satisfied and the Composite VAS score (all P < 0.05)
      were noted. CONCLUSIONS: Postprandial responses to PYY3-36, GIP and GLP-1
      concentrations were associated with VAS measures and the Composite VAS score
      following consumption of test meals in overweight adults.

PMID- 30096701
TI  - Factor analysis of organic soils for site discrimination in a forensic setting.
AB  - Organic soils are generally located in fluvial settings such as river floodplains
      that are commonly used for the disposal of bodies. Therefore, the aim of this
      study was to provide a protocol for the analysis of small amounts of organic
      soils for forensic purposes. The protocol was applied in five representative
      sites within the Curitiba metropolitan region (Brazil), with each site supplying
      four composite samples separated from one another by 3m. The soil samples were
      collected at a depth of 0 to 5cm. One gram of soil sample was used to determine
      the total elemental content and perform physical fractionation of the soil
      (>53MUm and <53MUm). For both soil size fractions, total C and N contents were
      determined, and the elements adsorbed to organic matter was determined only for
      the <53MUm size fraction (Na-pyrophosphate extraction). Chemometric multivariate
      analyses were conducted for the total data set, where more than 77% of the
      variation was explained by the first three factors. It was determined that Ca,
      Ba, and Mg adsorbed to organic matter, and total Ba, Ca, K, Mg, Mo, and C
      contents were most important in sample groupings. As expected in forensic
      science, the five sites were efficiently distinguishable from each other and the
      four replicates collected at the same individual site were clearly grouped. This
      protocol for sampling, chemical analysis, and data treatment of organic soils can
      be used in real crime situations.

PMID- 30096703
TI  - Possible immune adverse events as predictors of durable response to BRAF
      inhibitors in patients with BRAF V600-mutant metastatic melanoma.
AB  - BRAF inhibitors (BRAFi) and MEK inhibitors (MEKi) are among the cornerstones of
      metastatic melanoma therapy demonstrating excellent response rates with duration
      of 7-12 m. Long-term benefit from these agents was reported in patients with
      normal lactate dehydrogenase (LDH) and less than three disease sites. However, a
      treatment-dependent marker for long-term efficacy is lacking. Data suggest that
      immune-related adverse events (irAEs) are associated with clinical benefit in
      patients treated with immunotherapy and that response to BRAF/MEK therapy may
      have an underlying immune mechanism. We hypothesised that AEs with an underlying
      immune mechanism may be associated with a durable response to targeted therapy.
      We retrospectively identified a cohort of 78 BRAF V600-mutant metastatic melanoma
      patients treated with BRAFi or BRAFi + MEKi between November 2010 and November
      2013. Four treatment-related AEs including vitiligo, uveitis, erythema nodosum
      and keratitis sicca were defined as irAEs of interest. Retrospective analysis of
      AEs in relationship to progression-free survival (PFS), disease burden and LDH
      levels was performed. Median PFS (mPFS) for all patients was 7.5 months with
      responses ongoing in eight patients as of April 2017. Ten patients were
      identified with the AEs defined previously. Cox regression analysis revealed a
      very strong association between those AEs and PFS; mPFS was 42.8 m in patients
      with at least one AE versus 6.1 m in those without an AE (hazard ratio [HR] 0.22,
      p = 0.002). This association was independent of LDH levels and disease burden (HR
      0.24, p = 0.035). This analysis demonstrates a strong association between immune
      AEs and durable response to targeted therapy and may provide a treatment-related
      biomarker to estimate the outcome of therapy.

PMID- 30096702
TI  - A randomised phase II trial of capecitabine plus cisplatin versus S-1 plus
      cisplatin as a first-line treatment for advanced gastric cancer: Capecitabine
      plus cisplatin ascertainment versus S-1 plus cisplatin randomised PII trial
      (XParTS II).
AB  - BACKGROUND: Capecitabine plus cisplatin (XP) is a standard global regimen, while
      S-1 plus cisplatin (SP) is a Japanese standard for first-line treatment of
      advanced gastric cancer (AGC). We conducted a phase II trial comparing XP with SP
      for patients with AGC to confirm whether these regimens can be used as controls
      in a phase III study and to explore whether histological subtypes favour XP or
      SP. PATIENTS AND METHODS: Eligible patients were randomised to receive either S-1
      40 mg/m2 for 21 days plus cisplatin 60 mg/m2 (q5w) or capecitabine 1000 mg/m2 for
      14 days plus cisplatin 80 mg/m2 (q3w). The primary end-point was progression-free
      survival (PFS). The secondary end-points were overall survival (OS), overall
      response rate (ORR) and safety. RESULTS: In 110 eligible patients, 24-week PFS
      was higher in both groups (SP 50.9%, XP 43.5%) than the protocol-specified
      threshold of 40%. The median PFS for SP versus XP was 5.6 and 5.1 months (hazard
      ratio [HR], 1.126; p = 0.5626); OS was 13.5 and 12.6 months (HR, 0.942; p =
      0.7769) and the ORR was 42.4% and 69.4% (p = 0.0237), respectively. The most
      common grade >=3 adverse events with SP/XP were anaemia (16%/20%), neutropenia
      (9%/18%) and anorexia (18%/13%). Subgroup analysis by histological classification
      showed no statistical difference between treatments. CONCLUSIONS: XP and SP are
      comparable and can be recommended as control arms in a phase III study for AGC.
      Histological subtypes were not sensitive markers for the selection of XP or SP.
      CLINICAL TRIAL REGISTRATION: NCT00140624.

PMID- 30096705
TI  - A pooled analysis of published, basket trials in cancer medicine.
AB  - BACKGROUND: There is widespread interest in cancer basket trials. However, to
      date, there has been no formal analysis of all published basket trials. METHODS:
      We performed a systematic review to identify all published basket trials in
      cancer medicine. We included studies that (1) did not place restriction on tumour
      type and (2) used a biomarker for the basis of enrolment (3) administered at
      least one anti-cancer agent in prospective fashion and (4) reported responses by
      each tumour type included. We sought information regarding the tumour histology
      included and the response rate in basket trials. In addition, we used national
      cancer statistics to identify which tumour types have been overrepresented in
      basket studies (i.e. more representation in trials than their incidence would
      suggest) and those which are under-represented. RESULTS: We identified eight
      articles with a combined enrolment of 1176 patients were included in our
      analysis, representing over 33 tumour types. Ovarian and fallopian tube cancers
      221/1176 (19%), colorectal cancer 144/1176 (12%) and sarcoma 129 (11%) were the
      most common tumours represented, whereas renal cell cancer, seminoma, thymic
      carcinoma and neuroendocrine tumour and appendiceal carcinoma were the least
      represented with one case each. The overall response rate was 25%. Common cancers
      may be underrepresented compared with rarer tumour types (linear regression beta
      = 0.58, 95% confidence interval = -0.037-1.21) (slope < 1 implies under
      representation, >1 over-representation). CONCLUSIONS: We found that, to date,
      over 1100 patients have been enrolled on published basket studies. Common cancers
      may be underrepresented compared with rarer tumours. The overall response rate
      was 25%. Patients enrolling on basket trials should be counselled appropriately
      that although these studies are highly promising, most patients did not respond.
      Future targets and drugs may improve on these results.

PMID- 30096704
TI  - Outcomes by line of therapy and programmed death ligand 1 expression in patients
      with advanced melanoma treated with pembrolizumab or ipilimumab in KEYNOTE-006: A
      randomised clinical trial.
AB  - BACKGROUND: Predictive biomarkers of patients likely to benefit from anti
      programmed death 1 inhibitor therapy have clinical relevance. We examined whether
      line of therapy or tumour programmed death ligand 1 (PD-L1) expression affects
      the efficacy and safety of pembrolizumab, compared with ipilimumab, in advanced
      melanoma. METHODS: Of 834 patients enrolled in the randomised, open-label phase
      III KEYNOTE-006 study, 833 were included in this analysis. Patients were randomly
      assigned 1:1:1 to receive pembrolizumab 10 mg/kg every 2 or 3 weeks (for 24
      months) or ipilimumab 3 mg/kg every 3 weeks (for four doses) until disease
      progression/intolerable toxicity. This analysis evaluated progression-free
      survival (PFS), overall survival (OS) and objective response rate (ORR). Data cut
      off: 03 November 2016. RESULTS: Of the patients, 60.3% were male, 65.9% were
      treatment naive and 80.6% had PD-L1-positive tumours (median follow-up was 33.9
      months). Twenty-four-month survival rates were higher with pembrolizumab than
      with ipilimumab in treatment-naive (PFS 31.0% versus 14.6%; OS 58.0% versus
      44.7%) and previously treated patients (PFS 25.7% versus 11.3%; OS 49.2% versus
      37.9%). Twenty-four-month survival rates were higher with pembrolizumab than with
      ipilimumab in patients with PD-L1-positive tumours (PFS 33.2% versus 13.1%; OS
      58.4% versus 45.0%) and similar in PD-L1-negative tumours (PFS 14.9% versus NR
      [no data at 24 months for a PFS estimate]; OS 43.6% versus 31.8%). Safety of
      pembrolizumab by subgroup was consistent with previous reports. CONCLUSIONS:
      Findings support pembrolizumab monotherapy as standard of care in patients with
      advanced melanoma, regardless of first- or second-line therapy or PD-L1 status.
      CLINICALTRIALS. GOV IDENTIFIER: NCT01866319.

PMID- 30096706
TI  - Presence of 236U and 239,240Pu in soils from Southern Hemisphere.
AB  - 236U, 239Pu and 240Pu are present in soils mainly as a result of the local- and
      global-fallout from the atmospheric nuclear weapons tests carried out mainly in
      the 1950's and 1960's. In this work we provide new data on the presence of 236U
      and 239,240Pu in surface soils (i.e. up to 5 cm depth) from Chile and Africa. The
      results were obtained by low-energy Accelerator Mass Spectrometry (AMS). In the
      case of the Chilean samples, 236U/239Pu atom ratios show a high variability and
      are in general higher than the reported value for the global fallout in the
      Northern Hemisphere, ranging from 0.2 to 1.5. The 236U atomic concentrations
      range from 3.5 * 106 to 9.1 * 106 atoms/g, and are at least two orders of
      magnitude lower than the reported values in the Northern Hemisphere. The measured
      240Pu/239Pu atom ratio in soils from South-Africa and Mozambique are of about
      0.17, in agreement with the expected one for global-fallout at those coordinates.
      To best knowledge of the authors the present work is the first publication on
      236U concentrations and 236U/239Pu atom ratios in soils from South-America and
      Africa.

PMID- 30096707
TI  - The Uncoupled Assimilation of Carbon and Nitrogen from Urea and Glycine by the
      Bloom-forming Dinoflagellate Prorocentrum minimum.
AB  - The spread of harmful dinoflagellate blooms has been linked to the increasing
      availability of nitrogen, including its dissolved organic forms. The
      relationships between organic and inorganic nutrient uptake by dinoflagellates
      are not completely understood; moreover, it is not clear whether organic
      substances are used exclusively as nitrogen or also as carbon sources. We used
      laboratory culture experiments to investigate the concurrent uptake of glycine
      and nitrate by Prorocentrum minimum and estimate a role of two widespread organic
      substrates, glycine and urea, as carbon sources. Glycine uptake exceeded the
      uptake of nitrate when both nutrients were present in equal nitrogen amounts.
      Carbon of urea and glycine constituted only 0.4% and 1.3% of the total carbon
      uptake by cells, respectively, and this amount of carbon was disproportionately
      small compared to nitrogen taken up from the same organic substrates indicating
      uncoupling of organic carbon and nitrogen assimilation. We suggest that the
      observed uncoupling of organic nitrogen and carbon assimilation is a result of
      urea and glycine metabolic processing by urease and the glycine decarboxylation
      complex. We argue that such uncoupling reduces the net dissolved inorganic carbon
      (DIC) removal by dinoflagellates since the acquisition of nitrogen from urea and
      glycine leads to DIC release.

PMID- 30096708
TI  - Chaetoceros pauciramosus sp. nov. (Bacillariophyceae), a Widely Distributed
      Brackish Water Species in the C. lorenzianus Complex.
AB  - To understand the diversity of the diatom genus Chaetoceros Ehrenberg, the C.
      lorenzianus complex was previously chosen as a model and three new species were
      described. In the present study, yet another new species, Chaetoceros
      pauciramosus sp. nov., was discovered from Chinese tropical waters and the
      temperate south-eastern Baltic Sea. In the latter locality it has been known
      since 2003 and identified as C. cf lorenzianus, and now found to comprise a
      dominating component of the autumn phytoplankton community. Vegetative cells and
      resting spores were examined by light and electron microscopy. The LSU and SSU of
      the nuclear rDNA were sequenced. The characters suggesting that C. pauciramosus
      belongs to C. lorenzianus complex are: 1) the vegetative cells contain four or
      more chloroplasts, 2) the cells have stiff setae and form regular straight
      chains, 3) the terminal setae differ in the direction from the intercalary setae.
      The relationship was well-supported by molecular phylogenetic analyses inferred
      from both LSU and SSU markers. The primary valve of the resting spore has two
      conical elevations, each with dichotomously branching processes, similar to other
      species in the C. lorenzianus complex. Each process forms a tree-like structure
      with the pointed distal tips which possess one or two thin spikes, that
      distinguishes C. pauciramosus from allied taxa. In the phylogenetic trees,
      Chaetoceros pauciramosus clustered with C. elegans, in agreement with their
      morphologically similar resting spores.

PMID- 30096709
TI  - A Novel Method to Generate MNase Ladders Reveal Rapid Chromatin Remodeling upon
      Gametogenesis and Mating in Chlamydomonas.
AB  - To circumvent nuclei isolation for nucleosomal mapping of wild-type (cell walled)
      algal cells, we developed a quick and versatile methodology, by abrasion of whole
      cells (Chlamydomonas, Scenedesmus and yeast), allowing Micrococcal Nuclease
      (MNase) direct access to nuclear chromatin, in situ. Varying parameters such as
      bead abrasion, vortex and incubation conditions, we optimized capture of an
      'early digest' which may probe chromatin differentially, based on nucleosome
      accessibility. A comparison of such ladders across vegetative cells, gametes and
      zygotes revealed an increase in the average nucleosomal repeat length (+17-34nt)
      upon gametogenesis, indicating a trend of chromatin compaction. Using PCR, we
      compared promoter enrichment in increasing orders of fractionated nucleosomal
      repeats (mono-, di-, up to penta-), each differing in cleavability based on
      chromatin accessibility. Concordant with higher gene expression (mating locus),
      promoters revealed an enrichment in mono-nucleosomal fractions. Interestingly,
      the zygote specific gene, MT0828 displayed rapid remodelling from penta
      nucleosomal enrichment when completely repressed (vegetative), to intermediate
      states during gametogenesis (24hrs), which finally shifted to being largely mono
      nucleosomal, when induced (1h zygotes). Summarizing three candidate genes from
      the mating locus, we conclude that the MNase based 'Chromatin Accessibility
      Assay' can track a range of large-scale rapid chromatin remodelling transitions
      within the binaries of gene expression.

PMID- 30096710
TI  - Quantitative Response of Alexandrium catenella Cyst Dormancy to Cold Exposure.
AB  - Many dinoflagellate cysts experience dormancy, a reversible state that prevents
      germination during unfavorable periods. Several of these species also cause
      harmful algal blooms (HABs), so a quantitative understanding of dormancy cycling
      is desired for better prediction and mitigation of bloom impacts. This study
      examines the effect of cold exposure on the duration of dormancy in Alexandrium
      catenella, a HAB dinoflagellate that causes paralytic shellfish poisoning (PSP).
      Mature, dormant cysts from Nauset Marsh (Cape Cod, MA USA) were stored at low but
      above freezing temperatures for up to six months. Dormancy status was then
      determined at regular intervals using a germination assay. Dormancy timing was
      variable among temperatures and was shorter in colder treatments, but the
      differences collapse when temperature and duration of storage are scaled by
      chilling-units (CU), a common horticultural predictor of plant and insect
      development in response to weather. Cysts within Nauset meet a well-defined
      chilling requirement by late January, after which they are poised to germinate
      with the onset of favorable conditions in spring. Cysts thus modulate their
      dormancy cycles in response to their temperature history, enhancing the potential
      for new blooms and improving this species' adaptability to both unseasonable
      weather and new habitats/climate regimes.

PMID- 30096711
TI  - Establishment of a human iPSC line, IISHDOi004-A, from a patient with Usher
      syndrome associated with the mutation c.2276G>T; p.Cys759Phe in the USH2A gene.
AB  - A human iPSC line, IISHDOi004-A, from fibroblasts obtained from a patient with
      Usher syndrome, harboring a homozygous mutation in the USH2A gene (c.2276G>T;
      p.Cys759Phe) has been generated. Reprogramming factors Oct3/4, Sox2, Klf4, and c
      Myc were delivered using Sendai virus.

PMID- 30096712
TI  - Generation of a human Juvenile myelomonocytic leukemia iPSC line, CHOPi001-A,
      with a mutation in CBL.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative disorder of
      early childhood characterized by expansion of clonal myelomonocytic cells and
      hyperactive Ras/MAPK signaling. The disorder is caused by somatic and/or germline
      mutations in genes involved in the Ras/MAPK and JAK/STAT signaling pathways,
      including CBL. Here we describe the generation of an iPSC line with a homozygous
      CBL c.1111T->C (Y371H) mutation, designated CHOPJMML1854.

PMID- 30096713
TI  - What drives public transit organizations in the United States to adapt to extreme
      weather events?
AB  - Extreme weather events often disrupt the operation of public transit systems, and
      challenge the capacity of transit agencies to effectively respond to them. In
      this paper, we draw upon a recent nationwide survey of 273 public transit
      agencies in metropolitan regions across the United States to understand the
      factors that influence their scope of adaptation to anticipated climate risks. We
      find that a transit agency undertakes more adaptation measures when transit
      officials perceive greater risks and greater adaptive capacity of the agency, or
      when it experiences more severe extreme weather events. We also show that local
      institutional environment, in particular, political ideology, affects the scope
      of transit adaptation activities. Transit agencies that operate in more
      politically liberal counties tend to engage in more adaptation actions, while the
      effect of state-level ideology depends on the level of perceived influence from
      state governments.

PMID- 30096715
TI  - Diarylheptanoids from Curcuma phaeocaulis Suppress IL-6-Induced STAT3 Activation.
AB  - Three undescribed diarylheptanoids (3: -5: ) and six known curcuminoids (1, 2: ,
      and 6: -9: ) were obtained from the ethyl acetate-soluble fraction of an
      ethanolic extract of Curcuma phaeocaulis. Their chemical structures and absolute
      configurations were elucidated by high-resolution electrospray ionization mass
      spectrometry, nuclear magnetic resonance spectroscopy, circular dichroism
      spectroscopy, and the modified Mosher's method. Previous studies constructed
      Hep3B cells stably transfected with pSTAT3-Luc plasmid containing STAT3 binding
      site to discover STAT3 inhibitors from natural products. The STAT3 inhibitory
      activities of all isolates were measured in transfected Hep3B cells after
      treatment with IL-6. Compound 5: ((5R)-1,7-Bis(3,4-dimethoxyphenyl)-3-methoxy-1
      hepten-5-ol), demethoxycurcumin (7: ), and curcumin (8: ) exhibited significant
      inhibitory activity (IC50 values: 11.1, 1.9, and 1.6 uM, respectively).
      Furthermore, IL-6-induced phosphorylation of STAT3, and the mRNA expression
      levels of inflammation-related genes such as CRP, IL-1beta, ICAM-1, and SOCS3
      were significantly reduced by exposure to compound 5: . These data suggested that
      the inhibitory activity of 5: is associated with the suppression of STAT3
      phosphorylation. Thus, compound 5: may be a promising candidate for the treatment
      of cancer or inflammatory diseases related to the IL-6/STAT3 signaling pathway.

PMID- 30096714
TI  - Environmental impacts of nanomaterials.
AB  - Nanotechnology is currently one of the highest priority research fields in many
      countries due to its immense potentiality and economic impact. Nanotechnology
      involves the research, development, production, and processing of structures and
      materials on a nanometer scale in various fields of science, technology, health
      care, industries, and agriculture. As such, it has contributed to the gradual
      restructuring of many associated technologies. However, due to the uncertainties
      and irregularities in shape, size, and chemical compositions, the presence of
      certain nanomaterials may exert adverse impacts on the environment as well as
      human health. Concerns have thus been raised about the destiny, transport, and
      transformation of nanoparticles released into the environment. A critical
      evaluation of the current states of knowledge regarding the exposure and effects
      of nanomaterials on the environment and human health is discussed in this review.
      Recognition on the potential advantages and unintended dangers of nanomaterials
      to the environment and human health is critically important to pursue their
      development in the future.

PMID- 30096716
TI  - ?

PMID- 30096717
TI  - [Fibromyalgia Syndrome - Impact for Rehabilitation].
AB  - Fibromyalgia syndrome (FMS) is one of the most common chronic pain syndromes. In
      a representative survey, 2.1% of the German population was affected in 2013,
      whereby the diagnosis can only be made on the basis of subjective complaints.
      This article should provide concrete information on the disease concept,
      diagnosis, therapy, rehabilitation and socialmedical assessment at the FMS. The
      basis for this is the second update of the S3 guideline to the FMS adopted in
      2017.

PMID- 30096718
TI  - Recurrent acute pancreatitis due to pancreatic duct ascariasis in a young man.

PMID- 30096719
TI  - Choledochoduodenostomy for the treatment of portal cavernoma biliary stenosis to
      avoid bloody ERCP.

PMID- 30096720
TI  - Mechanistic Pathways of Selenium in the Treatment of Graves' Disease and Graves'
      Orbitopathy.
AB  - Based on the role of oxidative stress in the pathogenesis of Graves'
      hyperthyroidism and Graves' orbitopathy, the use of the antioxidant agent
      selenium has been proposed and several studies on the subject have been
      conducted, both in vitro and in vivo. Whereas a true benefit related to the use
      of selenium in patients with Graves' hyperthyroidism has been questioned, its use
      in patients with mild Graves' orbitopathy is generally believed to be beneficial
      because of which selenium has entered in the clinical practice for this eye
      condition.

PMID- 30096721
TI  - A Portrait of Pacing Profile of Cross-Country Skiers in the Vasaloppet 2004-2017.
AB  - The aim of the study was to examine the effect of performance group by race time
      (10 groups;<3 h, 3-4 h, and so on up to>12 h) on pacing in women (n=19,465) and
      men (n=164,454) finishers in the 'Vasaloppet' cross-country (XC) skiing race from
      2004 to 2017. The speed in the fastest and slowest split was analysed as a
      percentage of the mean race speed and pacing was defined as the difference (%)
      between the fastest and slowest split. Women had a larger pace range than men
      (44.0+/-10.6% versus 41.1+/-12.5%, respectively, p<0.001, d=0.25). An almost
      perfect relationship between performance group and pacing was observed in women
      (r=0.900, p<0.001) and men (r=0.908, p<0.001). A large main effect of performance
      on pacing was observed in women (p<0.001, eta2=0.292), where the smaller range
      was in the<4 h group (22.8+/-3.3%) and the largest in the 10-11 h group (49.2+/
      9.9%). In men, the corresponding values were 21.6+/-2.2% (<3 h group) and 51.6+/
      11.2% (10-11 h group; p<0.001, eta2=0.474). Based on these findings, it was
      concluded that fast XC skiers had relatively the most even pacing and pacing
      became less even with decreasing performance. This information is of practical
      value for coaches working with XC skiers to develop optimal sex- and performance
      tailored pacing strategies.

PMID- 30096722
TI  - Exercise Training-induced Modulation in Microenvironment of Rat Mammary
      Neoplasms.
AB  - Despite the importance attributed to exercise training in the breast cancer (BC)
      continuum, the underlying mechanisms modulating tumor behavior are unknown. We
      evaluated the effects of long-term moderate-exercise in the development of
      mammary tumors, and studied the microenvironment of infiltrative lesions, the
      amount of connective tissue, and balance between cellular
      proliferation/death.Fifty Sprague-Dawley rats, randomly assigned into four
      groups: two control groups (sedentary and exercised) and two models of BC groups
      (sedentary and exercised) induced by N-methyl-N-nitrosoureia (MNU), were
      sacrificed after 35 weeks of moderate-exercise, and all perceptible tumors were
      removed for histological and immunohistochemistry analysis.The median number of
      infiltrative-lesions per animal was lower in the MNU exercised animals (p=0.02).
      More than one histological pattern was identified, and papillary carcinoma was
      the most frequent in both groups. Within infiltrative-lesions, the number of
      immunopositive cells per MUm2 of Ki67 was lower in exercised animals (p=0.002).
      This presents increased cell death per MUm2 (p=0.019). Tumors from sedentary
      animals had a higher expression of collagen deposition (p=0.027).Long-term
      moderate-exercise has beneficial effects in tumor development with a diminished
      prevalence of malignancy. Within infiltrative-lesions, moderate-exercise improves
      the balance between cell-proliferation and cell-death with decreased connective
      tissue that suggests lower tumor aggressiveness.

PMID- 30096723
TI  - [Chances and Risk of New Intraocular Presbyopia Corrections Using Intraocular
      Lenses].

PMID- 30096724
TI  - [Amblyopia and refractive error].
AB  - Myopia is on the increase worldwide and will become a major challenge over the
      next decades in terms of secondary ophthalmologic complications. There are
      effective therapeutic options available to slow or prevent the progression of
      myopia. So far, it has not been investigated whether there are possible additive
      effects of these interventions. Further investigations - especially in Caucasian
      populations - are necessary to verify the study results available from Asia.
      There is limited data on how long further progression of myopia is preventable. A
      therapy appears reasonable as long as a progression of myopia is
      detectable.Consistent childhood amblyopia screening provides a cost-effective
      measure for the prevention of visual disturbances over the course of life. How
      this can be best integrated into the existing system of "U-investigations", must
      be clarified by the cost-bearers and professional associations. This discourse
      should be supported by close interdisciplinary exchange and further studies on
      the prevalence of different degrees of amblyopia. In addition, sensitive and
      specific or even multi-stage tests should be developed in order to implement an
      early detection that is cost-effective and saves resources.

PMID- 30096725
TI  - [Peripheral Exudative Haemorrhagic Chorioretinopathy: Course of Disease and
      Diagnosis - Including Wide-field Imaging of Associated Diseases Age-related
      Macular Degeneration and Polypoidal Choroidal Vasculopathy, Therapy].
AB  - PEHCR (peripheral exudative haemorrhagic chorioretinopathy) is a disease
      manifested clinically, particularly by subretinal bleeding, retinal exudates,
      retinal pigment epithelium detachments (RPE detachments), exudative retinal
      detachment and sub-RPE bleeding. The PEHCR lesion is often characterized by its
      polypoidal pattern, which is very similar to PCV (polypoidal choroidal
      vasculopathy) polyps. Diagnosis is best made with a wide-field ICGA (indocyanine
      green angiography). In approximately half of patients, macular changes in the
      form of drusen, up to exudative AMD (age-related macular degeneration), are
      detected in the affected eye or partner eye. Since there is very little
      literature directly available on PEHCR, this work also discusses the peripheral
      changes described in the context of AMD that were investigated with wide-field
      imaging.

PMID- 30096726
TI  - [Incidence and treatment of non-substance-induced delirium in general and
      specialist practices in Germany].

PMID- 30096727
TI  - Rejoinder to "on the alternative hypotheses for the win ratio".

PMID- 30096728
TI  - Chiral separation and determination of amino acid enantiomers in fruit juice by
      open-tubular nano liquid chromatography.
AB  - A novel chiral porous-layer stationary phase was developed for use in open
      tubular nano liquid chromatography. The stationary phase was prepared by an in
      situ polymerization of 3-chloro-2-hydroxypropylmethacrylate (HPMA-Cl) and
      ethylene dimethacrylate (EDMA). The reactive chloro groups at the surface of the
      porous stationary phase were reacted with beta-Cyclodextrin (beta-CD). The
      resulting morphology was characterized by using scanning electron microscopy
      (SEM) and Fourier-transform infrared spectroscopy (FT-IR). The chromatographic
      performance of the column was evaluated by hydrophilic interaction chromatography
      (HILIC). Amino acids were used as test solutes. The running buffer conditions for
      the enantioseparation were found to be 85% acetonitrile (ACN):10%MeOH: 5% H2 O at
      0.1% v/v trifluoro acetic acid (TFA) (flow rate: 800 nL/min). The
      enantioseparation provided high theoretical plate numbers up to 26 000 platesm-1
      . A good retention capacity within satisfactory retention times was also
      achieved. Real sample applicability of this column to the separation of amino
      acid enantiomers in fruit juice sample was demonstrated.

PMID- 30096730
TI  - Editorial.

PMID- 30096729
TI  - On the alternative hypotheses for the win ratio.
AB  - We extend the results of Luo et al. (, Biometrics 71, 139-145) regarding the
      alternative hypotheses for the win ratio from hazard orders to the upper quadrant
      stochastic order on the plane. This extension substantially widens the range of
      alternatives against which the win ratio is known to be consistent. It
      incorporates alternatives induced by simple and popular copula models that are
      left out by the characterization of Luo et al. (). We also discuss how our
      results may be generalized to win ratios in multivariate and stratified settings.

PMID- 30096731
TI  - Investigation of the distributional homogeneity on chlorpheniramine maleate
      tablets using NIR-CI.
AB  - Homogeneity is the basic element of pharmaceutical analysis. Distributional
      Homogeneity Index (DHI) was proposed to assess the distributional homogeneity of
      commercial chlorpheniramine maleate (CPM) tablets. Furthermore, the divergence
      value of DHI value from expectation DHI (value = 1) was calculated to obtain the
      CPM distributional homogeneity. The distribution of commercial CPM tablets from
      six brands was successfully visualized using near infrared chemical imaging (NIR
      CI) coupled with characteristic wavenumber method and binary image. Besides,
      content homogeneity of CPM was obtained through calculating the proportion of
      white region in the binary image. The result demonstrated that the distributional
      homogeneity of brand 4 was to be the best among all the brands, following by
      brand 2, brand 3, brand 5, brand 6 and brand 1. Furthermore, the sequence of the
      content uniformity was different from the distributional homogeneity, which
      demonstrated that content uniformity could not represent the distributional
      homogeneity. This work was a significant method guideline to assess the
      distributional homogeneity in pharmaceutical field.

PMID- 30096732
TI  - Application of FT/IR-ATR vibrational spectroscopy to reveal protein molecular
      structure of feedstock and co-products from Canadian and Chinese canola
      processing in relation to microorganism bio-degradation and enzyme bio-digestion.
AB  - The principal objective of this study was to apply FT/IR-ATR vibrational
      spectroscopy to inspect the relationship between rumen dry matter (DM) and
      protein degradation, rumen undegraded protein (RUP) intestinal digestion and
      processing induced protein molecular structure changes in feedstock (canola oil
      seeds) and co-products (canola meal) from bio-oil processing from different
      crushing plants in Canada and China. The rumen DM and protein degradation, rumen
      undegraded protein intestinal digestion and protein molecular structure affected
      by bio-oil processing were examined using in situ, three step in vitro digestion
      and Fourier transform infrared (FT/IR) molecular spectroscopy techniques,
      respectively. The results showed that the protein molecular structure; alpha
      helix height and alpha-helix to beta-sheet height ratio had a close association
      with rumen DM and protein degradation and rumen undegraded protein intestinal
      digestibility. Multiple regression analyses showed that protein beta-sheet height
      and alpha-helix to beta-sheet height ratio spectral intensity can be used to
      predict rumen DM and protein degradation, while intestinal digestibility of rumen
      undegraded protein can be predicted by alpha-helix height and beta-sheet height.
      In conclusion, the co-product canola meal from bio-oil processing is a good
      source of intestinally digestible protein. Rumen DM and protein degradation and
      intestinal digestibility of rumen undegraded protein are related to the protein
      molecular structures of the co-products affected by changes during bio-oil
      processing.

PMID- 30096733
TI  - Construction and characterization of a theranostic system based on
      graphene/manganese chelate.
AB  - Construction of hybrid systems that combine the cancer treatment and diagnosis
      agents on a single platform, known as theranostic systems, have received great
      attentions in the field of nanobiomedicine. Here, construction and
      characterization of a new multifunctional hybrid theranostic system based on RGO,
      PDA, BSA, DTPA-Mn(II), and MTX constituents, is presented. Accordingly, GO is
      partially reduced and simultaneously functionalized by dopamine, leading to
      reduced graphene oxide/polydopamine, RGO-PDA system; and then, the bovine serum
      albumin protein (BSA) is grafted onto this system. The obtained system, RGO-PDA
      BSA, is further decorated with diethylenetriaminepentaacetic acid-Mn(II) as
      diagnostic system and methotrexate as anticancer drug. Physicochemical
      characteristics of the RGO-PDA-BSA-DTPA-Mn(II)/MTX system are studied by Fourier
      transform infrared spectroscopy, atomic force microscopy, and electrochemical
      methods. The capturing ability of the prepared system for the cancer cells is
      evaluated through electrochemical impedance spectroscopy (EIS) and by using the
      4T1 cancer cells in comparison with L929 normal cells. The EIS results indicate
      that a degree of selectivity as 6.23 for GC-RGO-PDA-BSA-DTPA-Mn(II)/MTX electrode
      system toward 4T1 cells, which is larger than that obtained for this system
      toward the L929 cells. Similar analysis performed using the GC-RGO-PDA-DTPA
      Mn(II)/MTX system (having no BSA) indicate that the selectivity degree of the
      system is increased only by a factor of 1.6, implying that presence of BSA has
      increased the selectivity of the system for 4T1 cells by a factor of four. This
      behavior supports the crucial role of BSA in this process for 4T1 cells. Finally,
      the drug release study of RGO-PDA-BSA-DTPA-Mn(II)/MTX system is performed
      successfully at pH 7.4.

PMID- 30096734
TI  - Boosted activity of graphene encapsulated CoFe alloys by blending with activated
      carbon for oxygen reduction reaction.
AB  - The slow oxygen reduction reaction (ORR) hampers the efficiency of microbial fuel
      cells (MFCs) to a large extent, which usually requires catalysts to facilitate
      the electron transfer. The major challenge of the existed non-precious metals in
      place of the noble metal catalysts (Pt, Pd, Au et al.) for ORR is their low
      efficiency, which urgently needs special route to tackle this issue. Herein, we
      report a simple and convenient technique using prussian blue analogues as
      precursor to directly synthesize the N-doped graphene encapsulated CoFe alloy
      which is present in "Core-Shell" structure via calcination of Co2Fe(CN)6 in inert
      condition. The encapsulation of metal alloy within graphene shell immensely
      promotes the electron transfer from the encapsulated metals to the graphene
      surface. It efficiently optimizes the electronic structure of the as-synthesized
      catalyst and thereby triggers high ORR activity. The surrounding activated carbon
      (AC) contributes to the large pore structure and further offers a commodious
      route for the oxygen to gain electron. Therefore, the total resistance of air
      cathodes is significantly reduced from 17.300 Omega to 9.551 Omega and the
      electrochemical activity is greatly improved. The power performances of MFCs
      indicate that CoFe/C-10% presents the highest maximum power density (MPD) of 1616
      mW m-2, which is 5 times larger than that of the bare AC. It is well concluded
      that the graphene encapsulated CoFe alloy can be recognized as potential ORR
      catalyst for MFCs.

PMID- 30096735
TI  - Well-designed dopamine-imprinted polymer interface for selective and quantitative
      dopamine detection among catecholamines using a potentiometric biosensor.
AB  - We report a well-designed biointerface enabling the selective and quantitative
      detection of dopamine (DA) using a potentiometric biosensor. To enhance the
      detection selectivity of DA, a DA-templated molecularly imprinted polymer (DA
      MIP) was synthesized on the extended Au gate electrode of a field-effect
      transistor (FET) biosensor. For a quantitative DA analysis, the thickness of the
      DA-MIP was controlled to ca. 60 nm by surface-initiated atom transfer radical
      polymerization (SI-ATRP). In this process, the DA-MIP was copolymerized with
      vinylphenylboronic acid (vinyl-PBA), inducing molecular charges at the
      biointerface of the FET gate electrode. These charges were generated by the diol
      binding between PBA and dopamine (a catecholamine), and were directly detected as
      a change in surface potential. In fact, the surface potential at the gate of the
      DA-MIP-coated FET responded significantly to DA added at concentrations ranging
      from 40 nM to 20 MUM, whereas that of a non-imprinted polymer (NIP)-coated FET
      hardly changed over this range. Moreover, by measuring the kinetic parameters and
      electrochemical properties of well-designed devices with various added
      catecholamines, we confirmed that the DA-MIP-coated FET biosensor selectively and
      quantitatively detects DA.

PMID- 30096736
TI  - Lactate biosensing: The emerging point-of-care and personal health monitoring.
AB  - Lactate plays a crucial role in the anaerobic metabolic pathway of humans. In
      situations of oxygen deficit, its production increases; leading to several life
      threatening conditions such as hemorrhage, respiratory failure, trauma or
      ischemia from lactate acidosis. Lactate level detection and point-of-care (POC)
      monitoring in a fast, accurate and non-invasive manner is ultimately important
      for many health care applications. Optical and electrochemical techniques are
      employed in lactate sensing to achieve high sensitivity and selectivity,
      miniaturization, portability, simplicity, and low cost. To improve the
      selectivity and sensitivity, two important enzymes, lactate oxidase (LOx) and
      lactate dehydrogenese (LDH) are employed. Conventional methods for lactate
      detection are not fast enough to be used in point-of-care or personal health
      monitoring settings. Moreover, the existing point-of-care lactate sensing tools
      follow invasive or partially invasive sampling protocols such as finger pricking.
      In this review, a comprehensive overview of different lactate biosensing devices
      is presented. Particularly, the state-of-the-art and prospects of wearable, non
      invasive lactate sensing from different biofluids are discussed.

PMID- 30096737
TI  - Ultrasensitive electrochemiluminescence detection of Staphylococcus aureus via
      enzyme-free branched DNA signal amplification probe.
AB  - As a main cause of foodborne diseases, pathogenic bacteria have threatened the
      health and well-being of human communities. There is a need of fastness, accuracy
      and sensitivity in the method of detecting pathogenic bacteria. Classical signal
      amplification assays usually employ enzymes as biocatalysts to generate amplified
      signals, but the strict experimental conditions and complicated instruments
      restrict their application. In this work, we demonstrated an enzyme-free branched
      DNA (bDNA)-based signal amplification electrochemiluminescence (ECL) assay for
      ultrasensitive detection of pathogenic bacteria. Firstly, the capture probes and
      the amplification probes group were carefully designed by our research group. The
      detecting ECL signal of Staphylococcus aureus (S. aureus) was amplified by bDNA
      technique through the layer-by-layer signal amplification. The sensitivity was
      greatly improved by the use of multiple Ru(bpy)32+ (TBR)-labeled ECL probes.
      Secondly, the whole process of the detection was carried out in the absence of
      enzyme, without the need to control the reaction conditions strictly. Thirdly,
      the designed amplification probes group could be used for the analysis of other
      pathogenic bacteria, virus, tumor markers, biomarkers, etc. For the detection of
      S. aureus, the limit of detection (LOD) of the method was 2 pM for standard DNA,
      with the linear range from 20 pM to 100 nM. Last but not least, the LOD of the S.
      aureus asymmetric PCR products was 5 pM, with the linear range from 10 pM to 50
      nM. The sensitivity was 1-2 orders in magnitude higher than that of the common
      detection assays.

PMID- 30096738
TI  - Ultrasensitive label-free electrochemical immunosensor based on PVA-co-PE
      nanofibrous membrane for the detection of chloramphenicol residues in milk.
AB  - An ultrasensitive label-free amperometric immunosensor for the detection of
      chloramphenicol (CAP) residues in milk has been developed by using a screen
      printed carbon electrode laminated with a layer of poly (vinyl alcohol-co
      ethylene) (PVA-co-PE) nanofibrous membrane that is covalently immobilized with a
      CAP antibody (anti-CAP). The performance of the PVA-co-PE nanofiber membrane (PVA
      co-PE NFM) on the electrode was compared with a PVA-co-PE casted membrane (PVA-co
      PE CM), necessary fabrication steps and performance of the sensors were
      investigated by electrochemical impedance spectroscopy (EIS). The application of
      the PVA-co-PE NFM decreased the electron-transfer-resistance by about 4 times
      compared with a conventional PVA-co-PE casted membrane. Under the optimal
      conditions, the established immunosensor exhibited high sensitivity for
      determination of CAP in a range 0.01-10 ng mL-1, with a limit of detection of
      0.0047 ng mL-1. In addition to the good selectivity, reusability and stability
      over time, the prepared immunosensor was successfully used in the detection of
      CAP in milk samples without any pretreatment.

PMID- 30096740
TI  - Solution growth of 3D MnO2 mesh comprising 1D nanofibres as a novel sensor for
      selective and sensitive detection of biomolecules.
AB  - This work is the first report describing the solution grown 3D manganese oxide
      nanofibrous (MnO2 NFs) mesh and its potential for the simultaneous detection of
      biomolecules such as ascorbic acid and uric acid. The mesh is synthesized by a
      facile, one-pot, and cost-effective hydrothermal approach without using any
      template or structure directing compound. The morphology consists of randomly
      placed nanofibres possessing a diameter in the range of 10-25 nm, and length of
      several micron; constituting a highly porous and flexible material. The
      electrochemical potential was examined by recording cyclic voltammetry signals
      towards ascorbic acid and uric acid. The special mesh morphology offers a large
      surface area to promote enhanced electrochemical activity, and also provided a
      macroporous network that supported efficient mass transport. Additionally, the
      strong electronic cloud and roughness of MnO2 NFs mesh facilitated the fast
      oxidation of species at very low potential. The lower detection limit was found
      to be 1.33 uM (S/N = 3) and 1.03 uM (S/N = 3) for ascorbic acid and uric acid,
      respectively. The MnO2 NFs mesh modified electrodes can robustly differentiate
      both of them by giving well separate signals (Delta = 500 mV) indicating
      capability of the material towards selective detection. The sensor has been
      successfully applied to human blood and urine samples and the recoveries were
      found statistically significant. These results demonstrate the practical
      feasibility of 3D mesh to develop sensors for the accurate diagnosis of
      clinically important molecules.

PMID- 30096739
TI  - An ultrasensitive signal-on electrochemical aptasensor for ochratoxin A
      determination based on DNA controlled layer-by-layer assembly of dual gold
      nanoparticle conjugates.
AB  - In this paper, a novel ultrasensitive signal-on electrochemical aptasensor has
      been proposed for Ochratoxin A (OTA) assay based on DNA controlled layer-by-layer
      assembly of dual gold nanoparticle (AuNP) conjugates. To construct the
      aptasensor, the 1st AuNP conjugate was prepared by simultaneous immobilization of
      the capture probe 2 (CP2) and bridge probe (BP) onto the AuNPs. Then, OTA aptamer
      was loaded onto 1st AuNPs by hybridization with CP2. The 1st AuNP conjugate can
      be further immobilized onto the electrode by hybridization between BP and capture
      probe 1 (CP1), which was pre-immobilized on Au electrode. The 2nd AuNP conjugate
      was prepared by immobilization of ferrocene (Fc) tagged SH-signal probe (SSP).
      Due to the recognition between aptamer on 1st AuNP conjugate and OTA, CP2 was
      reformed in the ssDNA state, which can be utilized as the anchor for
      immobilization of 2nd AuNP conjugate for electrochemical signal reporting.
      Because of the high surface-to-volume ratio and good conductivity of AuNPs, this
      dual AuNPs assembled nanoarchitecture finally lead to greatly improved abilities
      to load a large number of Fc molecules and significantly amply the
      electrochemical response even at a low target concentration. Both qualitative and
      quantitative analysis of OTA were thus realized by differential pulse voltammetry
      (DPV) signals, resulting in an excellent detection limit of 0.001 ppb and a wide
      dynamic range from 0.001 to 500 ppb over 6 orders of magnitude. Moreover, the
      real sample analysis towards OTA spiked wine samples was favorable, implying a
      great potential for practical applications. We envision that this unique dual
      AuNP conjugate assembly strategy would pave a new avenue for the development of
      versatile signal amplified electrochemical aptasensors.

PMID- 30096741
TI  - Efficient mercury removal from wastewater by pistachio wood wastes-derived
      activated carbon prepared by chemical activation using a novel activating agent.
AB  - Ammonium nitrate (NH4NO3) with explosive characteristics at high temperatures was
      used as a novel activating reagent to prepare a surface-engineered activated
      carbon derived from pistachio wood wastes (PWAC). PWAC was characterized and
      compared with commercial activated carbon (CAC) by textural and morphological
      properties, surface chemistry, crystal structure, and surface elemental
      composition. The results indicated that the optimal conditions of PWAC
      preparation to obtain the highest mercury adsorption capacity were pyrolysis
      temperature (800  degrees C), pyrolysis time (2 h), and impregnation ratio (5%).
      PWAC was of highly regular-shaped and well-developed pores and possessed a large
      surface area (1448 m2/g) and high total pore volume (0.901 cm3/g). The batch
      experiments indicated that the adsorption process of Hg(II) was strongly
      dependent on the solution pH and reached fast equilibrium at approximately 30
      min. PWAC (202 mg/g) exhibited a significantly higher maximum adsorption capacity
      than commercial activated carbon (66.5 mg/g). Adsorbent-adsorbate dispersion
      interaction plays a major role in the adsorption mechanism, compared to the minor
      role played by pore filling and reduction mechanism. Overall, ammonium nitrate
      can be considered a newer activating reagent to prepare promising and low-cost
      PWAC for effectively Hg(II) removal from water media.

PMID- 30096742
TI  - Serious games as a catalyst for boundary crossing, collaboration and knowledge co
      creation in a watershed governance context.
AB  - Novel methods for enhancing collaboration and interactions are required to ensure
      that stakeholders and governments are able to develop a shared vision that
      supports sustainable watershed governance. Particular attention must be placed on
      integrating stakeholders who would otherwise have limited decision-making power.
      By crossing professional, ideological and jurisdictional boundaries,
      stakeholders' perspectives are more likely to change than when staying within
      those boundaries. This process, known as boundary crossing, requires boundary
      objects; either artifacts, people, or institutions that play a bridging role
      between different boundary spaces. For this study, serious games powered by
      scientific models are identified as potentially effective boundary objects. A
      serious game simulation called Aqua Republica was used to organize game
      simulation events allowing stakeholders to connect in an in-person, informal and
      novel setting. This exploratory research aims to study the role and impact of
      serious games as boundary objects to enhancing collaboration and knowledge co
      creation. The following research questions are addressed: (1) Do interactions
      increase over the course of a game simulation event? (2) Does the quality of
      interactions change over the course of a game simulation event? (3) Are the
      quantity and quality of interactions affected by pre-existing relationships? And
      if so, how? (4) How does the relationship between participants change over the
      course of a game simulation event? As part of this study, four game simulation
      events were organized that included students, professionals and diverse
      stakeholder groups working in watershed management contexts across Eastern Canada
      with 40 participants in total. Participants were divided into teams of 3-5
      members and were surveyed and their interactions recorded. An interaction and
      social network analysis of the audiovisual recordings of each game simulation
      event indicates that interactions between participants increase in both quantity
      and quality as the game progresses. The analysis shows that serious game
      simulations provide an intervention platform not only to facilitate cross
      boundary interactions, but also to strengthen relationships between diverse
      stakeholders, as expressed by an increase in mutual trust and empathy, as well as
      an improved understanding among the participants of the watershed system and the
      complex issues at stake.

PMID- 30096743
TI  - Comparing adaptive capacity index across scales: The case of Italy.
AB  - Measuring adaptive capacity as a key component of vulnerability assessments has
      become one of the most challenging topics in the climate change adaptation
      context. Numerous approaches, methodologies and conceptualizations have been
      proposed for analyzing adaptive capacity at different scales. Indicator-based
      assessments are usually applied to assess and quantify the adaptive capacity for
      the use of policy makers. Nevertheless, they encompass various implications
      regarding scale specificity and the robustness issues embedded in the choice of
      indicators selection, normalization and aggregation methods. We describe an
      adaptive capacity index developed for Italy's regional and sub-regional
      administrative levels, as a part of the National Climate Change Adaptation Plan,
      and that is further elaborated in this article. The index is built around four
      dimensions and ten indicators, analysed and processed by means of a principal
      component analysis and fuzzy logic techniques. As an innovative feature of our
      analysis, the sub-regional variability of the index feeds back into the regional
      level assessment. The results show that composite indices estimated at higher
      administrative or statistical levels neglect the inherent variability of
      performance at lower levels which may lead to suboptimal adaptation policies. By
      considering the intra-regional variability, different patterns of adaptive
      capacity can be observed at regional level as a result of the aggregation
      choices. Trade-offs should be made explicit for choosing aggregators that reflect
      the intended degree of compensation. Multiple scale assessments using a range of
      aggregators with different compensability are preferable. Our results show that
      within-region variability can be better demonstrated by bottom-up aggregation
      methods.

PMID- 30096744
TI  - The government capacity on industrial pollution management in Shanxi province: A
      response impulse analysis.
AB  - This study employs the Vector Auto-regression model with Generalized Response
      Impulse Function to analyse the dynamic nexus between economic growth and the
      industrial environmental pollution intensity for six specific pollutants in
      Shanxi province of China from 1995 to 2015. The result show there exists bi
      directional effects, with stronger impact running from economic development to
      industrial pollution is stronger. We also find the Shanxi government shows
      significant capacity in the management of industrial solid waste and waste gas.
      The provincial government has higher capacity in controlling Sulfur Dioxide
      compared to soot/dust. Our results verify the existence of Environmental Kuznets
      Curve through dynamic interactions between industrial pollution intensity and
      economic growth impulse. Three out of the six environmental pollution intensity
      responses are in the shape of inverted U curve. There are exceptions for three
      pollutants: N curve for Chemical Oxygen Demand and U curve for solid waste and
      waste gas.

PMID- 30096745
TI  - International trade of environmental goods in gravity models.
AB  - Environmental goods are goods used or produced by industry that reduce air and
      water pollution and optimize the use of resources in production. Despite several
      Sustainable Development Goals explicitly calling for resilient and sustainable
      development, the diffusion of such goods is still low, especially in developing
      countries. Only sporadic research on the determinants of international trade of
      environmental goods is available. Based on the OECD classification of
      environmental goods, this gap is filled by adopting a gravity model, using trade
      data over a time span of 15 years from 1999 to 2014 across 71 countries. The
      central message of this paper is that environmental regulatory stringency is a
      key determinant of environmental goods trade. It is specifically provided
      evidence that a substitution effect exists between environmental regulation
      stringency and trade of environmental goods. In line with empirical literature on
      traditional gravity models, increased capacity to innovate, cultural ties,
      geographical proximity and financial uncertainty also play a role.

PMID- 30096746
TI  - Machine learning for energy cost modelling in wastewater treatment plants.
AB  - Understanding the energy cost structure of wastewater treatment plants is a
      relevant topic for plant managers due to the high energy costs and significant
      saving potentials. Currently, energy cost models are generally generated using
      logarithmic, exponential or linear functions that could produce not accurate
      results when the relationship between variables is highly complex and non-linear.
      In order to overcome this issue, this paper proposes a new methodology based on
      machine-learning algorithms that perform better with complex datasets. In this
      paper, machine learning was used to generate high-performing energy cost models
      for wastewater treatment plants, using a database of 317 wastewater treatment
      plants located in north-west Europe. The most important variables in energy cost
      modelling were identified and for the first time, the energy price was used as
      model parameter and its importance evaluated.

PMID- 30096747
TI  - Dissipation of herbicides after repeated application in soils amended with green
      compost and sewage sludge.
AB  - Certain agricultural practices, such as the repeated application of herbicides or
      organic amendments to soil, can influence herbicide dissipation. This research
      has studied the effects of two repeated applications of mesotrione, pethoxamid,
      and triasulfuron on their dissipation rates in unamended soil (S) and soil
      amended with green compost (S+GC) or sewage sludge (S+SS). The dissipation
      experiment has also included an evaluation of the adsorption of the three
      herbicides by soils and of changes in soil dehydrogenase activity (DHA). The
      adsorption of the three herbicides by amended soils (Kf range 0.83-2.98) was
      higher than by unamended soil (Kf range 0.20-0.64). The adsorption coefficients
      (Kd) of mesotrione and triasulfuron were higher for S+SS, while that of
      pethoxamid was higher for S+GC, but no relationship between values for the time
      to 50% degradation (DT50) and adsorption coefficients could be determined. The
      repeated application of mesotrione decreased its dissipation rate in unamended
      soil (DT50 increased from 4.75 to 8.15 days) and amended soils (DT50 increased
      from 11.7 to 28.2 days in S+GC and from 17.7 to 37.9 in S+SS), whereas the
      repeated application of pethoxamid increased its dissipation rate in all the
      treatments, and the rate for triasulfuron increased only in amended soils. The
      highest DT50 values for pethoxamid (12.3 days) and triasulfuron (57.1 days) were
      in S+GC, and the lowest in S+SS (8.35 and 24.7 days). Soil DHA was stimulated by
      the presence of GC in the soil and by the first application of mesotrione. The
      second application of mesotrione and pethoxamid positively affected soil DHA, but
      this did not occur for triasulfuron. The repeated applications of herbicides and
      soil organic amendments have different effects on herbicide dissipation,
      adsorption, and soil DHA, and they should be taken into account when assessing
      soil quality and other potential environmental implications of pesticide use.

PMID- 30096748
TI  - Effect of light intensity and nutrients supply on microalgae cultivated in urban
      wastewater: Biomass production, lipids accumulation and settleability
      characteristics.
AB  - Microalgae cultivation systems fed with wastewater as source of nutrients
      represents the principal sustainable condition to produce microalgal biomass to
      be converted conveniently to biofuels. In order to optimize microalgae growth and
      their lipid content, the effect of light intensity and nutrients load in real
      wastewater was investigated through batch microalgal cultivation tests. A
      microalgal polyculture was used as inoculum and grown for 10 days in batch at
      different conditions of light intensity (i.e. 20, 50 and 100 MUmol s-1m-2) and
      nutrients concentration in wastewater. Experimental results showed that biomass
      productivity decreased for rich nutrients conditions and increased for high light
      intensities. The highest lipid mass content (29%) was found for high light
      intensity condition (100 MUmol s-1m-2). Furthermore, microalgae settleability
      tests, conducted at the end of the cultivation time, resulted in the highest
      biomass recovery efficiency (72%) for low light intensity and nutrients supply
      conditions.

PMID- 30096749
TI  - Sustainability assessment and causality nexus through ecosystem service
      accounting: The case of water purification in Europe.
AB  - The paper builds on the Supply and Use Tables module within the System of
      integrated Environmental and Economic Accounts - Experimental Ecosystem Accounts
      (SEEA EEA) developed by the UN. We explore the evolution of Supply and Use Tables
      from the System of National Accounts (SNA) to the System of integrated
      Environmental and Economic Accounts - Central Framework (SEEA CF) and then to the
      SEEA EEA, and we propose a further extension: we propose that ecosystem types
      should be treated as accounting units able to produce, consume and exhibit
      changes in regeneration and absorption rates. The implications are first
      explained in the methodological section and then shown in the application where
      the water purification service is tested against two major policy issues:
      sustainability assessment (we show how to assess whether the ecosystem service is
      used sustainably by comparing the quantification of potential and actual flow)
      and causality nexus (we quantify the connection between the value of agricultural
      production and that of the ecosystem service used). The paper highlights how the
      overall outcomes change when considering different scales. A contrast emerges,
      for example, between the positive balance at the continental scale, where water
      purification services appear to be used sustainably (thanks to the high potential
      flow of Northern European countries) and the negative balance of almost all
      European countries when considered at a national scale. Taking advantage of the
      experimental opportunities offered by operating with external satellite accounts,
      we are able to show how the proposed complementary tables could support policy
      action.

PMID- 30096750
TI  - Effects of soil components and solution inorganic cations on interactions of
      imidazolium-based ionic liquid with soils.
AB  - Effects of alkyl chain length of ionic liquid (IL), soil components and solution
      inorganic cations on a selected IL (1-methyl-3-octylimidazolium chloride,
      [OMIM]Cl) interaction with Chinese soils were investigated using batch sorption
      experiments. The results indicated that sorption energy was mainly controlled by
      chain length of [OMIM]Cl and contents of soil organic matter (SOM). [OMIM]Cl
      sorption on soils was mainly controlled by cation exchange process. Contributions
      of SOM and clay minerals (CMs) to [OMIM]Cl sorption were 7.3%-53.8% and 46.2%
      92.7%, respectively. SOM possessed higher energy cation-exchange binding sites
      than CMs. To predict the sorption of [OMIM]Cl on soils, a model for the
      relationship between sorption coefficient (Kd) and cation exchange capacity (CEC)
      from soil components (SOM and CMs, i.e., CECSOM and CECCMs) as well as solution
      concentration (Ce) was established: LogKd = Log(1.67*CECSOM + 3.22*CECCMs) -
      0.58LogCe. This model could provide a good prediction for sorption coefficients
      and the prediction errors were within 0.48 log unit. Competitive effects caused
      by inorganic cations followed the order of Ca2+ = Mg2+ > K+ > Na+. Concentrations
      and valence of coexisting ions both affect their competitive capability on
      [OMIM]Cl sorption. The finding of this study provided valuable information for
      evaluating the fate of [OMIM]Cl in soils.

PMID- 30096751
TI  - Unregulated disinfection By-products in drinking water in Quebec: A meta
      analysis.
AB  - Disinfection by-products (DBPs) are formed primarily by the reaction of natural
      organic matter and disinfectants. DBPs that are not regulated are referred to as
      unregulated DBPs (U-DBPs) and they are in majority in total DBPs. U-DBPs can be
      more toxic than regulated DBPs. U-DBPs such as haloacetonitriles (HANs),
      haloacetonitriles (HKs) and halonitromethanes (HNMs) are widely present in
      drinking water supplies in different regions of the world. This study
      investigated the occurrence of U-DBPs and their variability in drinking water in
      the Province of Quebec (Canada), using the water quality database of 40 municipal
      water systems generated by our research group. The concentrations of HANs, HKs,
      and their compounds, including chloropicrin (CPK), were highly variable in
      different water systems in Quebec. The concentration range of these U-DBPs is in
      line with drinking water concentration ranges in different regions of the world.
      Factors such as system size, water source, season, pH, total organic carbon
      content, free residual chlorine and disinfectant types cause significant
      variations in the concentrations of HANs, HKs and their constituent compounds,
      including CPK, in drinking water in Quebec. This information is valuable for
      decision making concerning source water selection, water distribution planning,
      water treatment plant design including disinfection, and overall drinking water
      quality management related to U-DBPs. Moreover, U-DBPs and regulated DBPs are
      strongly correlated, although the degree of correlation can vary with water
      source, system size and season, indicating that regulated DBPs can be used as
      surrogates of U-DBPs.

PMID- 30096753
TI  - Electrospun Silver Coated Polyacrylonitrile Membranes for Water Filtration
      Applications.
AB  - The scarcity of drinking water and the contamination of water sources in
      underdeveloped countries are serious problems that require immediate low-tech and
      low-cost solutions. In this study, we fabricated polyacrylonitrile (PAN) porous
      membranes coated with silver nanoparticles (AgNP) and demonstrated their use for
      water filtration and water treatment applications. The membranes were prepared by
      electrospinning a PAN solution and treating in a hydroxylamine (NH2OH) aqueous
      solution to form -C(NH2)N-OH groups that were used for functionalization (Ag+
      ions) of the membrane. The coordinated silver ions were then converted to silver
      nanoparticles. The microstructure of the membrane, water permeability,
      antimicrobial effect (using Escherichia coli), and particulate filtration
      capabilities were studied. This study verified that the membrane demonstrated a
      100% reduction for Gram-negative bacteria with an effective filtration rate of
      8.0 mL/cm2 min. Furthermore, the membrane was able to eliminate 60% of latex
      beads as small as 50 nm and over 80% of the 2 um beads via gravity filtration.
      This study demonstrated that PAN-AgNP membranes can be employed as antimicrobial
      membranes for the filtration of water in underdeveloped countries.

PMID- 30096754
TI  - Emergence of Nanoplatelet Light-Emitting Diodes.
AB  - Since 2014, nanoplatelet light-emitting diodes (NPL-LEDs) have been emerged as a
      new kind of LEDs. At first, NPL-LEDs are mainly realized by CdSe based NPLs.
      Since 2016, hybrid organic-inorganic perovskite NPLs are found to be effective to
      develop NPL-LEDs. In 2017, all-inorganic perovskite NPLs are also demonstrated
      for NPL-LEDs. Therefore, the development of NPL-LEDs is flourishing. In this
      review, the fundamental concepts of NPL-LEDs are first introduced, then the main
      approaches to realize NPL-LEDs are summarized and the recent progress of
      representative NPL-LEDs is highlighted, finally the challenges and opportunities
      for NPL-LEDs are presented.

PMID- 30096756
TI  - Effects of Heme Modulation on Ovophis and Trimeresurus Venom Activity in Human
      Plasma.
AB  - Geographic isolation and other factors result in evolution-driven diversity of
      the enzymatic composition of venom of pit vipers in the same genus. The present
      investigation sought to characterize venoms obtained from such genetically
      diverse Ovophis and Trimeresurus pit vipers utilizing thrombelastographic
      coagulation kinetic analyses. The coagulation kinetics of human plasma were
      assessed after exposure to venom obtained from two Ovophis and three Trimeresurus
      species. The potency of each venom was defined (ug/mL required to equivalently
      change coagulation); additionally, venoms were exposed to carbon monoxide (CO) or
      a metheme-inducing agent to modulate any enzyme-associated heme. All venoms had
      fibrinogenolytic activity, with four being CO-inhibitable. While Ovophis venoms
      had similar potency, one demonstrated the presence of a thrombin-like activity,
      whereas the other demonstrated a thrombin-generating activity. There was a 10
      fold difference in potency and 10-fold different vulnerability to CO inhibition
      between the Trimeresurus species. Metheme formation enhanced fibrinogenolytic
      like activity in both Ovophis species venoms, whereas the three Trimeresurus
      species venoms had fibrinogenolytic-like activity enhanced, inhibited, or not
      changed. This novel "venom kinetomic" approach has potential to identify
      clinically relevant enzymatic activity and assess efficacy of antivenoms between
      genetically and geographically diverse species.

PMID- 30096755
TI  - The Expanding Role of Ketogenic Diets in Adult Neurological Disorders.
AB  - The current review highlights the evidence supporting the use of ketogenic diet
      therapies in the management of adult epilepsy, adult malignant glioma and
      Alzheimer's disease. An overview of the scientific literature, both preclinical
      and clinical, in each area is presented and management strategies for addressing
      adverse effects and compliance are discussed.

PMID- 30096752
TI  - Mosquito Innate Immunity.
AB  - Mosquitoes live under the endless threat of infections from different kinds of
      pathogens such as bacteria, parasites, and viruses. The mosquito defends itself
      by employing both physical and physiological barriers that resist the entry of
      the pathogen and the subsequent establishment of the pathogen within the
      mosquito. However, if the pathogen does gain entry into the insect, the insect
      mounts a vigorous innate cellular and humoral immune response against the
      pathogen, thereby limiting the pathogen's propagation to nonpathogenic levels.
      This happens through three major mechanisms: phagocytosis, melanization, and
      lysis. During these processes, various signaling pathways that engage intense
      mosquito-pathogen interactions are activated. A critical overview of the mosquito
      immune system and latest information about the interaction between mosquitoes and
      pathogens are provided in this review. The conserved, innate immune pathways and
      specific anti-pathogenic strategies in mosquito midgut, hemolymph, salivary
      gland, and neural tissues for the control of pathogen propagation are discussed
      in detail.

PMID- 30096757
TI  - Genetic Polymorphisms Associated with the Neutrophil-Lymphocyte Ratio and Their
      Clinical Implications for Metabolic Risk Factors.
AB  - BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is a valuable prognostic or
      predictive biomarker in various diseases, but the genetic factors that underlie
      the NLR have not been studied. We attempted to investigate polymorphisms related
      to NLR phenotype and analyze their ability to predict metabolic risks. METHODS: A
      genome-wide association study was performed with log-transformed NLR using an
      Affymetrix AxiomTM KORV1.1-96 Array. Regression models for metabolic risk status
      were designed using the identified significant single-nucleotide polymorphisms
      (SNPs). RESULTS: We identified four SNPs near the TMEM116, NAA25, and PTPN11
      genes that were associated with the NLR. The top SNP associated with the log
      transformed NLR was rs76181728 in TMEM116. A case-control study was performed to
      analyze the metabolic risks associated with each SNP after adjusting for age,
      sex, and body mass index (BMI). Three SNPs displayed significant odds ratios
      (ORs) for increased blood pressure and increased waist circumference. In the
      regression model for metabolic syndrome, rs76181728 showed a significant
      association (OR = 1.465, 95% confidence interval (CI) = 1.091-1.969, P = 0.011)
      after adjustment for the NLR phenotype. CONCLUSIONS: We identified four novel
      SNPs that are associated with the NLR in healthy Koreans. SNPs in relevant genes
      might therefore serve as biomarkers for metabolic risks.

PMID- 30096759
TI  - Experiments on Temperature Changes of Microbolometer under Blackbody Radiation
      and Predictions Using Thermal Modeling by COMSOL Multiphysics Simulator.
AB  - In this study, we study a heat transfer model, with the surface of the
      microbolometer device receiving radiation from blackbody constructed using a
      COMSOL Multiphysics simulator. We have proposed three kinds of L-type 2-leg and 4
      leg with the pixel pitch of 35 MUm based on vanadium oxide absorbent membrane
      sandwiched with top passivated and bottom Si3N4 supporting films, respectively.
      Under the blackbody radiation, the surface temperature changes and distributions
      of these samples are simulated and analyzed in detail. The trend of change of the
      temperature dependent resistance of the four kinds of bolometer devices using the
      proposed heat transfer model is consistent with the actual results of the change
      of resistance of 4 samples irradiated with 325 K blackbody located in the front
      distance of 5 cm. In this paper, DeltaT indicates the averaged differences of the
      top temperature on the suspended membrane and the lowest temperature on the post
      of legs of the microbolometers. It is shown that DeltaT ~ 17 mK is larger in
      nominal 2-leg microbolometer device than that of 4-leg one and of 2-leg with 2
      MUm * 2 MUm central square hole and two 7.5 MUm * 2 MUm slits in suspended films.
      Additionally, only DeltaT ~ 5 mK with 4-leg microbolometer device under the same
      radiated energy of 325 K blackbody results from the larger total thermal
      conductance.

PMID- 30096758
TI  - Pin1 Modulation in Physiological Status and Neurodegeneration. Any Contribution
      to the Pathogenesis of Type 3 Diabetes?
AB  - Prolyl isomerases (Peptidylprolyl isomerase, PPIases) are enzymes that catalyze
      the isomerization between the cis/trans Pro conformations. Three subclasses
      belong to the class: FKBP (FK506 binding protein family), Cyclophilin and
      Parvulin family (Pin1 and Par14). Among Prolyl isomerases, Pin1 presents as
      distinctive feature, the ability of binding to the motif pSer/pThr-Pro that is
      phosphorylated by kinases. Modulation of Pin1 is implicated in cellular processes
      such as mitosis, differentiation and metabolism: The enzyme is dysregulated in
      many diverse pathological conditions, i.e., cancer progression, neurodegenerative
      (i.e., Alzheimer's diseases, AD) and metabolic disorders (i.e., type 2 diabetes,
      T2D). Indeed, Pin1 KO mice develop a complex phenotype of premature aging,
      cognitive impairment in elderly mice and neuronal degeneration resembling that of
      the AD in humans. In addition, since the molecule modulates glucose homeostasis
      in the brain and peripherally, Pin1 KO mice are resistant to diet-induced
      obesity, insulin resistance, peripheral glucose intolerance and diabetic vascular
      dysfunction. In this review, we revise first critically the role of Pin1 in
      neuronal development and differentiation and then focus on the in vivo studies
      that demonstrate its pivotal role in neurodegenerative processes and glucose
      homeostasis. We discuss evidence that enables us to speculate about the role of
      Pin1 as molecular link in the pathogenesis of type 3 diabetes i.e., the clinical
      association of dementia/AD and T2D.

PMID- 30096761
TI  - Process Parameter Effects on Biocompatible Thermoplastic Sheets Produced by
      Incremental Forming.
AB  - There has been increasing interest in the processes that enable part
      customization and small-batch production in recent years. The prosthetic sector,
      in which biocompatible materials are used, is one of the areas that requires
      these types of processes; Incremental Sheet Forming (ISF) technology can meet
      these requirements. However, the biocompatible thermoplastic polymers formed by
      this technology have not yet been tested. Hence, the aim of this paper is to
      cover this gap in our knowledge by analyzing the effects of process parameters on
      the ISF process with the aim of optimizing these parameters before the actual
      production of, in this case, customized prostheses. Tests with polycaprolactone
      (PCL) and ultra-high molecular weight polyethylene (UHMWPE) were performed.
      Maximum force, surface roughness and maximum depth were statistically analyzed by
      means of response surface methodology and survival analysis. Spindle speed and
      tool diameter were shown to be the most influential process parameters in terms
      of maximum forming force and surface roughness for both materials. In contrast,
      survival analysis applied to maximum depth showed a greater influence of tool
      diameter in PCL sheets and a greater influence of spindle speed in the case of
      UHMWPE.

PMID- 30096762
TI  - Design of a Multiband Global Navigation Satellite System Radio Frequency
      Interference Monitoring Front-End with Synchronized Secondary Sensors.
AB  - This paper investigates the challenges of developing a multi-frequency radio
      frequency interference (RFI) monitoring and characterization system that is
      optimized for ease of deployment and operation as well as low per unit cost. To
      achieve this, we explore the design and development of a multiband global
      navigation satellite system (GNSS) front-end which is intrinsically capable of
      synchronizing side channel information from non-RF sensors, such as inertial
      measurement units and integrated power meters, to allow the simultaneous
      production of substantial amounts of sampled spectrum while also allowing low
      cost, real-time monitoring and logging of detected RFI events. While the inertial
      measurement unit and barometer are not used in the RFI investigation discussed,
      the design features that provide for their precise synchronization with the RF
      sample stream are presented as design elements worth consideration. The designed
      system, referred to as Four Independent Tuners with Data-packing (FITWD), was
      utilized in a data collection campaign over multiple European and Scandinavian
      countries in support of the determination of the relative occurrence rates of
      L1/E1 and L5/E5a interference events and intensities where it proved itself a
      successful alternative to larger and more expensive commercial solutions. The
      dual conclusions reached were that it was possible to develop a compact low-cost,
      multi-channel radio frequency (RF) front-end that implicitly supported external
      data source synchronization, and that such monitoring systems or similar
      capabilities integrated within receivers are likely to be needed in the future
      due to the increasing occurrence rates of GNSS RFI events.

PMID- 30096760
TI  - Vitamin D and Endometrium: A Systematic Review of a Neglected Area of Research.
AB  - Growing evidence supports a role of vitamin D (VD) in reproductive health.
      Vitamin D receptor (VDR) is expressed in the ovary, endometrium, and myometrium.
      The biological actions of VD in fertility and reproductive tissues have been
      investigated but mainly using animal models. Conversely, the molecular data
      addressing the mechanisms underlying VD action in the physiologic endometrium and
      in endometrial pathologies are still scant. Levels of VDR expression according to
      the menstrual cycle are yet to be definitively clarified, possibly being lower in
      the proliferative compared to the secretory phase and in mid-secretory compared
      to early secretory phase. Endometrial tissue also expresses the enzymes involved
      in the metabolism of VD. The potential anti-proliferative and anti-inflammatory
      effects of VD for the treatment of endometriosis have been investigated in recent
      years. Treatment of ectopic endometrial cells with 1,25(OH)2D3 could
      significantly reduce cytokine-mediated inflammatory responses. An alteration of
      VD metabolism in terms of increased 24-hydroxylase mRNA and protein expression
      has been demonstrated in endometrial cancer, albeit not consistently. The effect
      of the active form of the vitamin as an anti-proliferative, pro-apoptotic, anti
      inflammatory, and differentiation-inducing agent has been demonstrated in various
      endometrial cancer cell lines.

PMID- 30096763
TI  - Synthesis of Heart/Dumbbell-Like CuO Functional Nanostructures for the
      Development of Uric Acid Biosensor.
AB  - It is always demanded to prepare a nanostructured material with prominent
      functional properties for the development of a new generation of devices. This
      study is focused on the synthesis of heart/dumbbell-like CuO nanostructures using
      a low-temperature aqueous chemical growth method with vitamin B12 as a soft
      template and growth directing agent. CuO nanostructures are characterized by
      scanning electron microscopy (SEM), X-ray diffraction (XRD), and X-ray
      photoelectron spectroscopy (XPS) techniques. CuO nanostructures are
      heart/dumbbell like in shape, exhibit high crystalline quality as demonstrated by
      XRD, and have no impurity as confirmed by XPS. Apparently, CuO material seems to
      be porous in structure, which can easily carry large amount of enzyme molecules,
      thus enhanced performance is shown for the determination of uric acid. The
      working linear range of the biosensor is 0.001 mM to 10 mM with a detection limit
      of 0.0005 mM and a sensitivity of 61.88 mV/decade. The presented uric acid
      biosensor is highly stable, repeatable, and reproducible. The analytical
      practicality of the proposed uric acid biosensor is also monitored. The
      fabrication methodology is inexpensive, simple, and scalable, which ensures the
      capitalization of the developed uric acid biosensor for commercialization. Also,
      CuO material can be used for various applications such as solar cells, lithium
      ion batteries, and supercapacitors.

PMID- 30096764
TI  - Bouganin, an Attractive Weapon for Immunotoxins.
AB  - Bougainvillea (Bougainvillea spectabilis Willd.) is a plant widely used in folk
      medicine and many extracts from different tissues of this plant have been
      employed against several pathologies. The observation that leaf extracts of
      Bougainvillea possess antiviral properties led to the purification and
      characterization of a protein, named bouganin, which exhibits typical
      characteristics of type 1 ribosome-inactivating proteins (RIPs). Beyond that,
      bouganin has some peculiarities, such as a higher activity on DNA with respect to
      ribosomal RNA, low systemic toxicity, and immunological properties quite
      different than other RIPs. The sequencing of bouganin and the knowledge of its
      three-dimensional structure allowed to obtain a not immunogenic mutant of
      bouganin. These features make bouganin a very attractive tool as a component of
      immunotoxins (ITs), chimeric proteins obtained by linking a toxin to a carrier
      molecule. Bouganin-containing ITs showed very promising results in the
      experimental treatment of both hematological and solid tumors, and one bouganin
      containing IT has entered Phase I clinical trial. In this review, we summarize
      the milestones of the research on bouganin such as bouganin chemico-physical
      characteristics, the structural properties and de-immunization studies. In
      addition, the in vitro and in vivo results obtained with bouganin-containing ITs
      are summarized.

PMID- 30096766
TI  - Stability Study and Identification of Degradation Products of Caffeoylgluconic
      Acid Derivatives from Fructus Euodiae.
AB  - Caffeoylgluconic acid derivatives are characteristic constituents isolated from
      the aqueous extract of Fructus Euodiae. In this research focusing on
      caffeoylgluconic acid derivatives, trans-caffeoyl-6-O-d-gluconic acid (CGA),
      trans-caffeoyl-6-O-d-gluconic acid methyl ester (CGA-ME), and trans-caffeoyl-6-O
      d-glucono-gamma-lactone (CGA-LT), a systematic study of stability was performed
      under different temperatures and pH levels by ultra performance liquid
      chromatography-diode array detector (UPLC-DAD) and ultra performance liquid
      chromatography-diode array detector/electrospray ionization-quadrupole-time of
      flight mass spectrometry (UPLC-DAD/ESI-Q-TOF MS). From the concentration-time
      curves and sensitivity index (SeI), it was found that compared to CGA, which is
      inert to the variation of temperature and pH in the tested range, CGA-ME and CGA
      LT were more sensitive, with stabilities more likely to be influenced by
      temperature. Considering the stability index (StI), the integrated stability of
      CGA was the best, and that of CGA-ME was the worst. In terms of the quasi
      molecular and fragment ions of the tested compounds, the degradation products
      were identified or tentatively characterized, which could shed light on the
      degradation pathways. CGA-ME and CGA-LT were easily converted to CGA by
      hydrolytic reaction, all of which were susceptible to the formation of isomers.
      This study elucidated the degradation mechanism of caffeoylgluconic acid
      derivatives, contributing to better guidance on manufacturing and controlling the
      quality of drugs.

PMID- 30096767
TI  - Mechanisms of LPS-Induced Acute Kidney Injury in Neonatal and Adult Rats.
AB  - Neonatal sepsis is one of the major causes of mortality and morbidity in
      newborns, greatly associated with severe acute kidney injury (AKI) and failure.
      Handling of newborns with kidney damage can be significantly different compared
      to adults, and it is necessary to consider the individuality of an organism's
      response to systemic inflammation. In this study, we used lipopolysaccharide
      (LPS)-mediated acute kidney injury model to study mechanisms of kidney cells
      damage in neonatal and adult rats. We found LPS-associated oxidative stress was
      more severe in adults compared to neonates, as judged by levels of carbonylated
      proteins and products of lipids peroxidation. In both models, LPS-mediated septic
      simulation caused apoptosis of kidney cells, albeit to a different degree.
      Elevated levels of proliferating cell nuclear antigen (PCNA) in the kidney
      dropped after LPS administration in neonates but increased in adults. Renal
      fibrosis, as estimated by smooth muscle actin levels, was significantly higher in
      adult kidneys, whereas these changes were less profound in LPS-treated neonatal
      kidneys. We concluded that in LPS-mediated AKI model, renal cells of neonatal
      rats were more tolerant to oxidative stress and suffered less from long-term
      pathological consequences, such as fibrosis. In addition, we assume that by some
      features LPS administration simulates the conditions of accelerated aging.

PMID- 30096768
TI  - Trans-Ferulic Acid-4-beta-Glucoside Alleviates Cold-Induced Oxidative Stress and
      Promotes Cold Tolerance.
AB  - Trans-ferulic acid-4-beta-glucoside (C16H20O9, TFA-4beta-G) is a monomer
      extracted from the Chinese medicine called radix aconiti carmichaeli (Fuzi). To
      date, research on this substance is lacking. Here, we found that trans-ferulic
      acid-4-beta-glucoside effectively promoted cold acclimatization in mice via
      increased heat production and alleviation of oxidative stress in a cold
      environment. Thus, our work indicates that ferulic acid-4-beta-glucoside is a
      potential therapeutic candidate for prevention and treatment of cold stress
      injury.

PMID- 30096765
TI  - Scaffolds as Structural Tools for Bone-Targeted Drug Delivery.
AB  - Although bone has a high potential to regenerate itself after damage and injury,
      the efficacious repair of large bone defects resulting from resection, trauma or
      non-union fractures still requires the implantation of bone grafts. Materials
      science, in conjunction with biotechnology, can satisfy these needs by developing
      artificial bones, synthetic substitutes and organ implants. In particular, recent
      advances in materials science have provided several innovations, underlying the
      increasing importance of biomaterials in this field. To address the increasing
      need for improved bone substitutes, tissue engineering seeks to create synthetic,
      three-dimensional scaffolds made from organic or inorganic materials,
      incorporating drugs and growth factors, to induce new bone tissue formation. This
      review emphasizes recent progress in materials science that allows reliable
      scaffolds to be synthesized for targeted drug delivery in bone regeneration, also
      with respect to past directions no longer considered promising. A general
      overview concerning modeling approaches suitable for the discussed systems is
      also provided.

PMID- 30096770
TI  - Special Issue: Molecular Properties and the Applications of Peptide Nucleic
      Acids.
AB  - Polyamide analogs of DNA, or peptide nucleic acid (PNA), were first proposed in
      1991 by a group of chemists and biochemists in a memorable Science paper
      [1].[...].

PMID- 30096769
TI  - Aggregation of Human Trophoblast Cells into Three-Dimensional Culture System
      Enhances Anti-Inflammatory Characteristics through Cytoskeleton Regulation.
AB  - BACKGROUND: Three-dimensional (3D) culture changes cell characteristics and
      function, suggesting that 3D culture provides a more physiologically relevant
      environment for cells compared with 2D culture. We investigated the differences
      in cell functions depending on the culture model in human trophoblast cells
      (Sw.71). METHODS: Sw.71 cells were incubated in 2D monolayers or simple 3D
      spheroids. After incubation, cells were corrected to assess RNA-seq transcriptome
      or protein expression, and culture medium were corrected to detect cytokines. To
      clarify the role of actin cytoskeleton, spheroid Sw.71 cells were treated
      mycalolide B (inhibitor of actin polymerization) in a 3D culture. RESULTS: RNA
      seq transcriptome analysis, results revealed that 3D-cultured cells had a
      different transcriptional profile compared with 2D-cultured cells, especially
      regarding inflammation-related molecules. Although interleukin-6 (IL-6) mRNA
      level was higher in 3D-culured cells, its secretion levels were higher in 2D
      cultured cells. In addition, the levels of mRNA and protein expression of regnase
      1, regulatory RNase of inflammatory cytokine, significantly increased in 3D
      culture, suggesting post-translational modification of IL-6 mRNA via regnase-1.
      Treatment with mycalolide B reduced cell-to-cell contact to build 3D formation
      and increased expression of actin cytoskeleton, resulting in increased IL-6
      secretin. CONCLUSION: Cell dimensionality plays an essential role in governing
      the spatiotemporal cellular outcomes, including inflammatory cytokine production
      and its negative regulation associated with regnase-1.

PMID- 30096771
TI  - Dietary Change during Pregnancy and Women's Reasons for Change.
AB  - Women often make dietary changes during pregnancy; however, dietary modifications
      and reasons for changes are not well studied. We aimed to describe the dietary
      changes made during pregnancy, describe reasons for dietary changes, and
      determine what changes aligned with recommendations. Pregnant women (n = 379)
      recruited to the Alberta Pregnancy Outcomes and Nutrition (APrON) study in
      2009/2010 completed a questionnaire in which they described dietary changes made
      during pregnancy and reasons for those changes. Changes and reasons were coded
      into categories. Women commonly reported increasing their intake of milk
      products, fruit, and sweet items and commonly decreased or eliminated intake of
      caffeine, alcohol, and meats. Women frequently reduced intake of foods for the
      baby's health and increased foods to satisfy cravings. Changes made commonly
      aligned with recommendations for caffeine, alcohol intake, food safety, milk and
      alternatives, and fruit. Changes contrary to recommendations were common for fish
      and meats. The dietary changes women make during pregnancy appear to reflect
      women's efforts to balance physiological changes accompanying pregnancy with the
      desire for healthy pregnancy outcomes. Understanding the reasons behind dietary
      change during pregnancy will help researchers and health professionals design
      effective strategies and public health messages to promote healthier pregnancies.

PMID- 30096774
TI  - Effect of Die Geometry on the Formability of 5052 Aluminum Alloy in
      Electromagnetic Impaction Deformation.
AB  - The formability of aluminum alloy sheet in electromagnetic impaction deformation
      has attracted the attention of numerous researchers for the past decades.
      However, the influences of die geometry and high-speed impaction electromagnetic
      deformation on formability have not been well established, thereby resulting in
      the formability of the sheet not being developed fully. In this study, the
      influence of die geometry on the formability of 5052 aluminum alloy in
      electromagnetic deformation was investigated by comparing the formability of 5052
      aluminum alloys formed using a hemispherical die and a cylindrical die. The
      intriguing finding is that the formability of the 5052 aluminum alloy formed
      using a cylindrical die is considerably higher than that formed using a
      hemispherical die. Therefore, die geometry significantly influences the
      formability of 5052 aluminum alloy. The influence of die geometry on the
      formability of 5052 aluminum alloy in high-speed impaction electromagnetic
      deformation was explained in terms of strain rate, pressure stress, and stress
      state. This investigation enhances insight into the interaction between sheets
      and dies, and provides a reference for the studying influence of dies on the
      forming limit of sheets in high-speed impaction deformation.

PMID- 30096773
TI  - Histologic and Histomorphometric Analysis of Bone Regeneration with Bovine
      Grafting Material after 24 Months of Healing. A Case Report.
AB  - : Anorganic bovine bone mineral matrix (ABBMM) has been reported to have
      osteoconductive properties and no inflammatory or adverse responses when used as
      grafting material in sinus augmentation procedures. However, controversy remains
      in regard to degradation rate of ABBMM. The aim of this study was to
      histologically and histomorphometrically evaluate the degradation of ABBMM in
      human bone samples obtained in one patient 24 months after sinus augmentation.
      MATERIALS AND METHODS: The histologic and histomorphometric analysis was
      performed by means of light microscopy in three specimens harvested from the same
      patient, Results: After 24 months the tissue pattern appeared to be composed of
      residual particles, some in close contact with the newly formed bone, others
      separated by translucent areas and osteoid tissues. Newly-formed bone presented
      different levels of maturation and numerous osteocytes, with greater numbers in
      bone closer to the grafted particles (27.3% vs. 11.2%, p < 0.05). The
      histomorphometric analysis showed mean values of 40.84% newly-formed bone, 33.58%
      residual graft material, 23.84% marrow spaces, and 1.69% osteoid tissue,
      Conclusions: Even though ABBMM underwent considerable resorption, a great amount
      of residual grafting material was still present after two years of healing
      following sinus augmentation. This study confirms that the bovine grafts can be
      classified as long-term degradation materials.

PMID- 30096772
TI  - An Ethnopharmacological, Phytochemical and Pharmacological Review on Lignans from
      Mexican Bursera spp.
AB  - The genus Bursera belongs to the family Burseraceae and has been used in
      traditional Mexican medicine for treating various pathophysiological disorders.
      The most representative phytochemicals isolated from this genus are terpenoids
      and lignans. Lignans are phenolic metabolites known for their antioxidant,
      apoptotic, anti-cancer, anti-inflammatory, anti-bacterial, anti-viral, anti
      fungal, and anti-protozoal properties. Though the genus includes more than 100
      species, we have attempted to summarize the biological activities of the 34
      lignans isolated from selected Mexican Bursera plants.

PMID- 30096775
TI  - Dietary Inflammatory Index and Biomarkers of Lipoprotein Metabolism, Inflammation
      and Glucose Homeostasis in Adults.
AB  - Accumulating evidence identifies diet and inflammation as potential mechanisms
      contributing to cardiometabolic risk. However, inconsistent reports regarding
      dietary inflammatory potential, biomarkers of cardiometabolic health and
      metabolic syndrome (MetS) risk exist. Our objective was to examine the
      relationships between a food frequency questionnaire (FFQ)-derived dietary
      inflammatory index (DII(r)), biomarkers of lipoprotein metabolism, inflammation
      and glucose homeostasis and MetS risk in a cross-sectional sample of 1992 adults.
      Energy-adjusted DII (E-DII) scores derived from an FFQ were calculated.
      Lipoprotein particle size and subclass concentrations were measured using nuclear
      magnetic resonance (NMR) spectroscopy. Serum acute-phase reactants,
      adipocytokines, pro-inflammatory cytokines and white blood cell (WBC) counts were
      determined. Insulin resistance was calculated by homeostasis model assessment
      (HOMA-IR). Our data indicate that a more pro-inflammatory diet, reflected by
      higher E-DII scores, was associated with potentially pro-atherogenic lipoprotein
      profiles characterised by increased numbers of large very low density lipoprotein
      (VLDL), small dense low density lipoprotein (LDL) and high density lipoprotein
      (HDL) particles and less large LDL and HDL particles (all p < 0.001).
      Inflammatory profiling identified a range of adverse phenotypes among those with
      higher E-DII scores, including higher complement component C3 (C3), C-reactive
      protein (CRP), (both p < 0.05), interleukin 6 (IL-6) and tumour necrosis factor
      (TNF)-alpha concentrations, higher WBC counts and neutrophil to lymphocyte ratio
      (NLR) and lower adiponectin levels (all p < 0.001). MetS risk was increased among
      those with higher E-DII scores (OR 1.37, 95% CI (1.01, 1.88), p < 0.05), after
      adjusting for potential confounders. In conclusion, habitual intake of a more pro
      inflammatory diet is associated with unfavourable lipoprotein and inflammatory
      profiles and increased MetS risk.

PMID- 30096778
TI  - PRG: A Distance Measurement Algorithm Based on Phase Regeneration.
AB  - With the booming development of the Internet of things (IoT) industry, the demand
      of positioning technology in various IoT application scenarios is also greatly
      increased. To meet the positioning requirements of the IoT application, we
      propose a distance measurement method based on phase regeneration that can
      provide positioning capability for IoT applications in indoor and outdoor
      environments. The PRG algorithm consists of two phases: coarse ranging phase and
      fine ranging phase. Fingerprint positioning algorithm based on Gradient Boost
      Decision Tree (GBDT) is used to determine coarse distance. The host machine
      measures the difference between the transmitted carrier phase and the received
      regenerative carrier phase to fix the fine distance and then the coarse distance
      is used to determine the carrier phase integer ambiguity. Finally, high precision
      ranging is realized. Simulation results show that the PRG method can achieve
      range finding with decimeter level precision under the 10 MHz subcarrier
      frequency.

PMID- 30096777
TI  - miRNA-34c Overexpression Causes Dendritic Loss and Memory Decline.
AB  - Microribonucleic acids (miRNAs) play a pivotal role in numerous aspects of the
      nervous system and are increasingly recognized as key regulators in
      neurodegenerative diseases. This study hypothesized that miR-34c, a miRNA
      expressed in mammalian hippocampi whose expression level can alter the
      hippocampal dendritic spine density, could induce memory impairment akin to that
      of patients with Alzheimer's disease (AD) in mice. In this study, we showed that
      miR-34c overexpression in hippocampal neurons negatively regulated dendritic
      length and spine density. Hippocampal neurons transfected with miR-34c had
      shorter dendrites on average and fewer filopodia and spines than those not
      transfected with miR-34c (control mice). Because dendrites and synapses are key
      sites for signal transduction and fundamental structures for memory formation and
      storage, disrupted dendrites can contribute to AD. Therefore, we supposed that
      miR-34c, through its effects on dendritic spine density, influences synaptic
      plasticity and plays a key role in AD pathogenesis.

PMID- 30096776
TI  - The Role of Cannabis within an Emerging Perspective on Schizophrenia.
AB  - Background: Approximately 0.5% of the population is diagnosed with some form of
      schizophrenia, under the prevailing view that the pathology is best treated using
      pharmaceutical medications that act on monoamine receptors. Methods: We briefly
      review evidence on the impact of environmental forces, particularly the effect of
      autoimmune activity, in the expression of schizophrenic profiles and the role of
      Cannabis therapy for regulating immunological functioning. Results: A review of
      the literature shows that phytocannabinoid consumption may be a safe and
      effective treatment option for schizophrenia as a primary or adjunctive therapy.
      Conclusions: Emerging research suggests that Cannabis can be used as a treatment
      for schizophrenia within a broader etiological perspective that focuses on
      environmental, autoimmune, and neuroinflammatory causes of the disorder, offering
      a fresh start and newfound hope for those suffering from this debilitating and
      poorly understood disease.

PMID- 30096780
TI  - Non-Ionizing Radiation for Cardiac Human Amniotic Mesenchymal Stromal Cell
      Commitment: A Physical Strategy in Regenerative Medicine.
AB  - Cell therapy is an innovative strategy for tissue repair, since adult stem cells
      could have limited regenerative ability as in the case of myocardial damage. This
      leads to a local contractile dysfunction due to scar formation. For these
      reasons, refining strategy approaches for "in vitro" stem cell commitment,
      preparatory to the "in vivo" stem cell differentiation, is imperative. In this
      work, we isolated and characterized at molecular and cellular level, human
      Amniotic Mesenchymal Stromal Cells (hAMSCs) and exposed them to a physical
      Extremely Low Frequency Electromagnetic Field (ELF-EMF) stimulus and to a
      chemical Nitric Oxide treatment. Physically exposed cells showed a decrease of
      cell proliferation and no change in metabolic activity, cell vitality and
      apoptotic rate. An increase in the mRNA expression of cardiac and angiogenic
      differentiation markers, confirmed at the translational level, was also
      highlighted in exposed cells. Our data, for the first time, provide evidence that
      physical ELF-EMF stimulus (7 Hz, 2.5 uT), similarly to the chemical treatment, is
      able to trigger hAMSC cardiac commitment. More importantly, we also observed that
      only the physical stimulus is able to induce both types of commitments
      contemporarily (cardiac and angiogenic), suggesting its potential use to obtain a
      better regenerative response in cell-therapy protocols.

PMID- 30096779
TI  - Wine: An Aspiring Agent in Promoting Longevity and Preventing Chronic Diseases.
AB  - INTRODUCTION: Moderate wine consumption is a characteristic of the Mediterranean
      diet. Studies around the world have shown a beneficial effect of moderate alcohol
      intake, especially wine, on health. This review aims to critically summarise the
      most recent studies that investigate the beneficial effects of moderate wine
      intake on human health. METHODS: The PubMed database was comprehensively searched
      to identify trials published from 2013 to 2018 that investigated the association
      between moderate wine consumption and health. RESULTS: The most recent studies
      confirm the valuable role of moderate wine consumption, especially red wine, in
      the prevention and treatment of chronic diseases such as cardiovascular disease,
      metabolic syndrome, cognitive decline, depression, and cancer. In the meantime,
      recent studies also highlight the beneficial role of red wine against oxidative
      stress and in favour of desirable gut bacteria. The beneficial role of red wine
      has been attributed to its phytochemical compounds, as highlighted by clinical
      trials, where the effect of red wine has been compared to white wine, non
      alcoholic wine, other alcoholic drinks, and water. CONCLUSIONS: Moderate wine
      intake, at 1-2 glasses per day as part of the Mediterranean diet, has been
      positively associated with human health promotion, disease prevention, and
      disease prognosis.

PMID- 30096782
TI  - Comparison of Vocalization Patterns in Piglets Which Were Crushed to Those Which
      Underwent Human Restraint.
AB  - Though many studies focused on piglet crushing utilizing piglet vocalizations to
      test sow response, none have verified the properties of test vocalizations
      against actual crushing events. Ten sows were observed 48 h after parturition,
      and crushing events were recorded from all sows. When a crushing event occurred,
      a second piglet within the same litter was used to solicit a vocalization through
      manual restraint to compare restrained piglets' call properties to those of
      crushed piglets'. A total of 659 Restrained calls and 631 Crushed calls were
      collected. Variables were gathered at the loudest point in a call, and as an
      average across the entire call. Crushed piglets had a lower fundamental frequency
      (p < 0.01; Crushed: 523.57 +/- 210.6 Hz; Restrained: 1214.86 +/- 203.2 Hz) and
      narrower bandwidth (p < 0.01; Crushed: 4897.01 +/- 587.3 Hz; Restrained: 6674.99
      +/- 574.0 Hz) when analyzed at the loudest portion of a call. Overall, piglets
      which were crushed had a lower mean peak frequency than those which were
      restrained (p = 0.01; 1497.08 +/- 239.4 Hz and 2566.12 +/- 235.0 Hz,
      respectively). Future research should focus on measuring sow reactivity to
      Crushed and Restrained piglets to continue to improve research practices.

PMID- 30096781
TI  - Toxin-Pathogen Synergy Reshaping Detoxification and Antioxidant Defense Mechanism
      of Oligonychus afrasiaticus (McGregor).
AB  - Current study reveals the likelihood to use pathogen and toxin mutually as an
      effective and eco-friendly strategy for Oligonychus afrasiaticus (McGregor)
      management, which could reduce toxicant dose and host killing time. Therefore,
      phytol and Beauveria bassiana in different proportions were evaluated to
      determine their effectiveness. Prior to ascertaining host mortality and defense
      mechanisms, we have recorded in vitro action of phytol using different
      concentrations (0.70, 1.40, 2.10, 2.80, and 3.50 mg/mL) against B. bassiana
      suspension. In vitro compatibility assays revealed that growth parameters
      (vegetative growth, sporulation, and viability) of B. bassiana were least
      affected by the action of phytol at all tested concentrations. Biological Index
      of B. bassiana exhibited compatibility with phytol allowed us to conduct Joint
      toxicity bioassays in which phytol and spores mixed in different proportions in
      order to attain maximum treatment effect in terms of high mortality at low
      concentration under short time. Results revealed that joint-application exhibited
      both synergistic (treatments with higher proportions of phytol), and antagonistic
      interaction (treatments with higher proportions of spores) interactions.
      Biochemical mechanisms involved in host antioxidant and detoxification response
      were explored by quantifying their respective enzymatic activities. Lethality of
      different treatments induced different patterns of detoxification enzymes
      including glutathione S-transferase (GST) and acetylcholinesterase (AchE).
      Overall, the least potent treatments (20% phytol:80% spores, and 40% phytol:60%
      spores) established in the current study induced relatively higher GST and AchE
      activities. On the other hand, the most potent treatment (80% phytol:20% spores)
      at its maximum concentration exhibited negligible relative GST and AchE
      activities. Antioxidant enzyme activities of CAT and SOD measured in the current
      study showed moderate to complex interaction might because of toxin-pathogen
      remarkable synergy. This study suggested that joint application of phytol with B.
      bassiana spores have shown tremendous acaricidal potential and found to be
      promising new strategy for controlling old world date mites.

PMID- 30096783
TI  - Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit
      ATP-Induced IL-1beta Release by Pulmonary Epithelial Cells.
AB  - Phosphocholine-modified bacterial cell wall components are virulence factors
      enabling immune evasion and permanent colonization of the mammalian host, by
      mechanisms that are poorly understood. Recently, we demonstrated that free
      phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from
      Haemophilus influenzae, an opportunistic pathogen of the upper and lower airways,
      function as unconventional nicotinic agonists and efficiently inhibit the ATP
      induced release of monocytic IL-1beta. We hypothesize that H. influenzae PC-LOS
      exert similar effects on pulmonary epithelial cells and on the complex lung
      tissue. The human lung carcinoma-derived epithelial cell lines A549 and Calu-3
      were primed with lipopolysaccharide from Escherichia coli followed by stimulation
      with ATP in the presence or absence of PC or PC-LOS or LOS devoid of PC. The
      involvement of nicotinic acetylcholine receptors was tested using specific
      antagonists. We demonstrate that PC and PC-LOS efficiently inhibit ATP-mediated
      IL-1beta release by A549 and Calu-3 cells via nicotinic acetylcholine receptors
      containing subunits alpha7, alpha9, and/or alpha10. Primed precision-cut lung
      slices behaved similarly. We conclude that H. influenzae hijacked an endogenous
      anti-inflammatory cholinergic control mechanism of the lung to evade innate
      immune responses of the host. These findings may pave the way towards a host
      centered antibiotic treatment of chronic airway infections with H. influenzae.

PMID- 30096785
TI  - Does a Supplemental Low-Protein Diet Decrease Mortality and Adverse Events After
      Commencing Dialysis? A Nationwide Cohort Study.
AB  - BACKGROUND: A beneficial effect of a ketoanalogue-supplemented low-protein diet
      (sLPD) in postponing dialysis has been demonstrated in numerous previous studies.
      However, evidence regarding its effect on long-term survival is limited. Our
      study assessed the long-term outcomes of patients on an sLPD after commencing
      dialysis. METHODS: This retrospective study examined patients with new-onset end
      stage renal disease with permanent dialysis between 2001 and 2013, extracted from
      Taiwan's National Health Insurance Research Database. Patients who received more
      than 3 months of sLPD treatment in the year preceding the start of dialysis were
      extracted. The outcomes studied were all-cause mortality, infection rate, and
      major cardiac and cerebrovascular events (MACCEs). RESULTS: After propensity
      score matching, the sLPD group (n = 2607) showed a lower risk of all-cause
      mortality (23.1% vs. 27.6%, hazard ratio (HR) 0.77, 95% confidence interval (CI)
      0.70-0.84), MACCEs (19.2% vs. 21.5%, HR 0.86, 95% CI 0.78-0.94), and infection
      related death (9.9% vs. 12.5%, HR 0.76, 95% CI 0.67-0.87) than the non-sLPD group
      did. CONCLUSION: We found that sLPD treatment might be safe without long-term
      negative consequences after dialysis treatment.

PMID- 30096784
TI  - Movement Disorders Related to Gluten Sensitivity: A Systematic Review.
AB  - Gluten related disorders (GRD) represent a wide spectrum of clinical
      manifestations that are triggered by the ingestion of gluten. Coeliac disease
      (CD) or gluten sensitive enteropathy is the most widely recognised, but extra
      intestinal manifestations have also been increasingly identified and reported.
      Such manifestations may exist in the absence of enteropathy. Gluten sensitivity
      (GS) is another term that has been used to include all GRD, including those where
      there is serological positivity for GS related antibodies in the absence of an
      enteropathy. Gluten ataxia (GA) is the commonest extraintestinal neurological
      manifestation and it has been the subject of many publications. Other movement
      disorders (MDs) have also been reported in the context of GS. The aim of this
      review was to assess the current available medical literature concerning MDs and
      GS with and without enteropathy. A systematic search was performed while using
      PubMed database. A total of 48 articles met the inclusion criteria and were
      included in the present review. This review highlights that the phenomenology of
      gluten related MDs is broader than GA and demonstrates that gluten-free diet
      (GFD) is beneficial in a great percentage of such cases.

PMID- 30096786
TI  - Gaps in the Evidence on Population Interventions to Reduce Consumption of Sugars:
      A Review of Reviews.
AB  - There is currently considerable attention directed to identifying promising
      interventions to reduce consumption of sugars among populations around the world.
      A review of systematic reviews was conducted to identify gaps in the evidence on
      such interventions. Medline, EMBASE CINAHL, and the Cochrane Database of
      Systematic Reviews were searched to identify systematic reviews published in
      English from January 2005 to May 2017 and considering research on interventions
      to reduce sugar intake. Twelve systematic reviews that considered price changes,
      interventions to alter the food available within specific environments, and
      health promotion and education programs were examined. Each of the identified
      reviews focused on sugar-sweetened beverages (SSBs). The existing literature
      provides some promising indications in terms of the potential of interventions to
      reduce SSB consumption among populations. However, a common thread is the limited
      scope of available evidence, combined with the heterogeneity of methods and
      measures used in existing studies, which limits conclusions that can be reached
      regarding the effectiveness of interventions. Reviewed studies typically had
      limited follow-up periods, making it difficult to assess the sustainability of
      effects. Further, there is a lack of studies that address the complex context
      within which interventions are implemented and evaluated, and little is known
      about the cost-effectiveness of interventions. Identified gaps speak to the need
      for a more holistic approach to sources of sugars beyond SSBs, consensus on
      measures and methods, attention to the implementation of interventions in
      relation to context, and careful monitoring to identify intended and unintended
      consequences.

PMID- 30096788
TI  - GRC-Sensing: An Architecture to Measure Acoustic Pollution Based on Crowdsensing.
AB  - Noise pollution is an emerging and challenging problem of all large metropolitan
      areas, affecting the health of citizens in multiple ways. Therefore, obtaining a
      detailed and real-time map of noise in cities becomes of the utmost importance
      for authorities to take preventive measures. Until now, these measurements were
      limited to occasional sampling made by specialized companies, that mainly focus
      on major roads. In this paper, we propose an alternative approach to this problem
      based on crowdsensing. Our proposed architecture empowers participating citizens
      by allowing them to seamlessly, and based on their context, sample the noise in
      their surrounding environment. This allows us to provide a global and detailed
      view of noise levels around the city, including places traditionally not
      monitored due to poor accessibility, even while using their vehicles. In the
      paper, we detail how the different relevant issues in our architecture, i.e.,
      smartphone calibration, measurement adequacy, server design, and client-server
      interaction, were solved, and we have validated them in real scenarios to
      illustrate the potential of the solution achieved.

PMID- 30096789
TI  - Erratum: Cost-Effectiveness of Product Reformulation in Response to the Health
      Star Rating Food Labelling System in Australia; Nutrients 2018, 10, 614.
AB  - The authors have requested that the following changes be made to their paper
      [...].

PMID- 30096790
TI  - A Framework of Industrialized Building Assessment in China Based on the
      Structural Equation Model.
AB  - Compared with the conventional building, the industrialized building (IB)
      promotes the sustainable development of the construction industry, which will
      become a growth trend in the future. Nevertheless, the progress of industrialized
      building is intimately affected through the scientific evaluating mechanism,
      which still requires more research. Thus, this study establishes a conceptual
      framework of industrialized building assessment (IBA), which is validated through
      exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The
      impact between efficiency and the other five dimensions are studied by the
      structural equations model (SEM). The findings indicated that the conceptual
      framework is valid, and the efficiency has a positive impact on economic factors,
      livability, safety, environmental factors, and social benefits. Consequently, the
      improvement of efficiency has turned out to be the primary issue for improving
      the growth of the industrialized building. This research explores the basic
      framework of industrialized building assessment and provides a basis to establish
      a comprehensive and precise industrial building evaluation mechanism in the near
      future.

PMID- 30096787
TI  - mTORC Inhibitors as Broad-Spectrum Therapeutics for Age-Related Diseases.
AB  - Chronological age represents the greatest risk factor for many life-threatening
      diseases, including neurodegeneration, cancer, and cardiovascular disease; ageing
      also increases susceptibility to infectious disease. Current efforts to tackle
      individual diseases may have little impact on the overall healthspan of older
      individuals, who would still be vulnerable to other age-related pathologies.
      However, recent progress in ageing research has highlighted the accumulation of
      senescent cells with chronological age as a probable underlying cause of
      pathological ageing. Cellular senescence is an essentially irreversible
      proliferation arrest mechanism that has important roles in development, wound
      healing, and preventing cancer, but it may limit tissue function and cause
      widespread inflammation with age. The serine/threonine kinase mTOR (mechanistic
      target of rapamycin) is a regulatory nexus that is heavily implicated in both
      ageing and senescence. Excitingly, a growing body of research has highlighted
      rapamycin and other mTOR inhibitors as promising treatments for a broad spectrum
      of age-related pathologies, including neurodegeneration, cancer,
      immunosenescence, osteoporosis, rheumatoid arthritis, age-related blindness,
      diabetic nephropathy, muscular dystrophy, and cardiovascular disease. In this
      review, we assess the use of mTOR inhibitors to treat age-related pathologies,
      discuss possible molecular mechanisms of action where evidence is available, and
      consider strategies to minimize undesirable side effects. We also emphasize the
      urgent need for reliable, non-invasive biomarkers of senescence and biological
      ageing to better monitor the efficacy of any healthy ageing therapy.

PMID- 30096791
TI  - UnPAXing the Divergent Roles of PAX2 and PAX8 in High-Grade Serous Ovarian
      Cancer.
AB  - High-grade serous ovarian cancer is a deadly disease that can originate from the
      fallopian tube or the ovarian surface epithelium. The PAX (paired box) genes PAX2
      and PAX8 are lineage-specific transcription factors required during development
      of the fallopian tube but not in the development of the ovary. PAX2 expression is
      lost early in serous cancer progression, while PAX8 is expressed ubiquitously.
      These proteins are implicated in migration, invasion, proliferation, cell
      survival, stem cell maintenance, and tumor growth. Hence, targeting PAX2 and PAX8
      represents a promising drug strategy that could inhibit these pro-tumorigenic
      effects. In this review, we examine the implications of PAX2 and PAX8 expression
      in the cell of origin of serous cancer and their potential efficacy as drug
      targets by summarizing their role in the molecular pathogenesis of ovarian
      cancer.

PMID- 30096793
TI  - EcoHealth and the Determinants of Health: Perspectives of a Small Subset of
      Canadian Academics in the EcoHealth Community.
AB  - EcoHealth is an emerging field that examines the complex relationships among
      humans, animals, and the environment, and how these relationships affect the
      health of each of these domains. The different types of determinants of health
      greatly influence human health and well-being. Therefore, EcoHealth's ability to
      improve human, animal, and environmental health and well-being is, in part,
      influenced by its ability to acknowledge and integrate the determinants of
      health. However, our previous research demonstrates that the academic EcoHealth
      literature had a low, uneven engagement with the determinants of health.
      Accordingly, to make sense of this gap, our research aim is to better understand
      the views of a small subset of the Canadian EcoHealth community about EcoHealth
      and the determinants of health relative to EcoHealth. We used a qualitative
      research design involving seven semi-structured interviews, which were analyzed
      using thematic analysis. Our findings suggest a tension across themes and a lack
      of conceptual engagement with the determinants of health. As we consider a future
      with rapid, unsustainable changes, we expect the identification and integration
      of the different types of determinants of health within EcoHealth to be
      imperative for EcoHealth to attain its goal of improving the health and well
      being of humans, animals, and the environment.

PMID- 30096794
TI  - Redox Biology of Right-Sided Heart Failure.
AB  - Right-sided heart failure is the major cause of death among patients who suffer
      from various forms of pulmonary hypertension and congenital heart disease. The
      right ventricle (RV) and left ventricle (LV) originate from different progenitor
      cells and function against very different blood pressures. However, differences
      between the RV and LV formed after birth have not been well defined. Work from
      our laboratory and others has accumulated evidence that redox signaling,
      oxidative stress and antioxidant regulation are important components that define
      the RV/LV differences. The present article summarizes the progress in
      understanding the roles of redox biology in the RV chamber-specificity.
      Understanding the mechanisms of RV/LV differences should help develop selective
      therapeutic strategies to help patients who are susceptible to and suffering from
      right-sided heart failure. Modulations of redox biology may provide effective
      therapeutic avenues for these conditions.

PMID- 30096795
TI  - Predicting Condom Use among Undergraduate Students Based on the Theory of Planned
      Behaviour, Coquimbo, Chile, 2016.
AB  - Background: Sexually transmitted infections and pregnancy in adolescents are
      acknowledged public health problems in many countries. Although it is known that
      the proper use of condoms allows avoiding these health problems, their use in
      Chile is still limited, for unknown reasons. Objective: Based on planned
      behavioural theory, the aim was to validate a behaviour model regarding condom
      use by measuring the influence of the variables that predict this use among
      Chilean university students. Methods: A cross-sectional descriptive study was
      carried out in October 2016 among 151 Chilean university students belonging to
      the health and engineering areas. The information was collected through a self
      administered survey. The sample was divided into two groups: stable and not
      stable relationships. Partial least squares (PLS) regression was used for the
      analysis. Results: It was possible to explain the condom use of the students by
      57%. The attitude was the main variable related to the intention of using
      condoms, together with the perceived behavioural control. Additionally, there are
      statistically significant differences in the variables that predict condom use
      among students with stable relations compared to those without a stable
      relationship. Conclusions: The planned behavioural theory is useful for
      predicting condom use behaviour when students have a stable partner.

PMID- 30096792
TI  - Human Milk Oligosaccharides and Immune System Development.
AB  - Maternal milk contains compounds that may affect newborn immunity. Among these
      are a group of oligosaccharides that are synthesized in the mammary gland from
      lactose; these oligosaccharides have been termed human milk oligosaccharides
      (HMOs). The amount of HMOs present in human milk is greater than the amount of
      protein. In fact, HMOs are the third-most abundant solid component in maternal
      milk after lactose and lipids, and are thus considered to be key components. The
      importance of HMOs may be explained by their inhibitory effects on the adhesion
      of microorganisms to the intestinal mucosa, the growth of pathogens through the
      production of bacteriocins and organic acids, and the expression of genes that
      are involved in inflammation. This review begins with short descriptions of the
      basic structures of HMOs and the gut immune system, continues with the beneficial
      effects of HMOs shown in cell and animal studies, and it ends with the
      observational and randomized controlled trials carried out in humans to date,
      with particular emphasis on their effect on immune system development. HMOs seem
      to protect breastfed infants against microbial infections. The protective effect
      has been found to be exerted through cell signaling and cell-to-cell recognition
      events, enrichment of the protective gut microbiota, the modulation of microbial
      adhesion, and the invasion of the infant intestinal mucosa. In addition, infants
      fed formula supplemented with selected HMOs exhibit a pattern of inflammatory
      cytokines closer to that of exclusively breastfed infants. Unfortunately, the
      positive effects found in preclinical studies have not been substantiated in the
      few randomized, double-blinded, multicenter, controlled trials that are
      available, perhaps partly because these studies focus on aspects other than the
      immune response (e.g., growth, tolerance, and stool microbiota).

PMID- 30096796
TI  - Exploring the Impact of the Biofloc Rearing System and an Oral WSSV Challenge on
      the Intestinal Bacteriome of Litopenaeus vannamei.
AB  - We provide a global overview of the intestinal bacteriome of Litopenaeus vannamei
      in two rearing systems and after an oral challenge by the White spot syndrome
      virus (WSSV). By using a high-throughput 16S rRNA gene sequencing technology, we
      identified and compared the composition and abundance of bacterial communities
      from the midgut of shrimp reared in the super-intensive biofloc technology (BFT)
      and clear seawater system (CWS). The predominant bacterial group belonged to the
      phylum Proteobacteria, followed by the phyla Bacteroidetes, Actinobacteria, and
      Firmicutes. Within Proteobacteria, the family Vibrionaceae, which includes
      opportunistic shrimp pathogens, was more abundant in CWS than in BFT-reared
      shrimp. Whereas the families Rhodobacteraceae and Enterobacteriaceae accounted
      for almost 20% of the bacterial communities of shrimp cultured in BFT, they
      corresponded to less than 3% in CWS-reared animals. Interestingly, the WSSV
      challenge dramatically changed the bacterial communities in terms of composition
      and abundance in comparison to its related unchallenged group. Proteobacteria
      remained the dominant phylum. Vibrionaceae was the most affected in BFT-reared
      shrimp (from 11.35 to 20.80%). By contrast, in CWS-reared animals the abundance
      of this family decreased from 68.23 to 23.38%. Our results provide new evidence
      on the influence of both abiotic and biotic factors on the gut bacteriome of
      aquatic species of commercial interest.

PMID- 30096797
TI  - Effect of Milk Fermented with Lactobacillus fermentum on the Inflammatory
      Response in Mice.
AB  - Currently, the effect of fermented milk on the T-helper 17 response in
      inflammatory bowel diseases (IBDs) is unknown. The aim of the present study was
      to evaluate the effect of milks fermented with Lactobacillus fermentum on the
      Th1/Th17 response in a murine model of mild IBD. Exopolysaccharide (EPS), lactic
      acid (LA), and total protein (TP) contents and bacterial concentration were
      determined. Male C57Bl/6 mice intragastrically received either raw (FM) or
      pasteurized (PFM) fermented milk before and during a dextran sulfate infusion
      protocol. Blood, spleen, and colon samples were collected at Weeks 6 and 10. IL
      6, IL-10, and TNFalpha were determined in serum, and IL-17, IL-23, and IFNgamma
      were determined in intestinal mucosa and serum. The FM groups did not differ in
      cell concentration, LA, or TP content (p > 0.05); FM-J28 had the highest EPS
      content. Spleen weight and colon length did not differ among the FM groups (p >
      0.05). In the FM-J20 and PFM-J20 groups, IL-17 and IFNgamma decreased, and the IL
      10 concentration was enhanced (p < 0.05) at Week 6. IL-6, TNFalpha, IL-23, and
      IFNgamma did not differ in serum and mucosa (p > 0.05), and IL-17 was lowest in
      FM-J28 and FM-J20. Therefore, FM appears to potentially play a role in decreasing
      the Th17 response. However, further studies are needed to elucidate the FM
      mediated anti-inflammatory mechanisms in IBD.

PMID- 30096798
TI  - Sonic Hedgehog Medulloblastoma Cancer Stem Cells Mirnome and Transcriptome
      Highlight Novel Functional Networks.
AB  - Molecular classification has improved the knowledge of medulloblastoma (MB), the
      most common malignant brain tumour in children, however current treatments cause
      severe side effects in patients. Cancer stem cells (CSCs) have been described in
      MB and represent a sub population characterised by self-renewal and the ability
      to generate tumour cells, thus representing the reservoir of the tumour. To
      investigate molecular pathways that characterise this sub population, we isolated
      CSCs from Sonic Hedgehog Medulloblastoma (SHH MB) arisen in Patched 1 (Ptch1)
      heterozygous mice, and performed miRNA- and mRNA-sequencing. Comparison of the
      miRNA-sequencing of SHH MB CSCs with that obtained from cerebellar Neural Stem
      Cells (NSCs), allowed us to obtain a SHH MB CSC miRNA differential signature.
      Pathway enrichment analysis in SHH MB CSCs mirnome and transcriptome was
      performed and revealed a series of enriched pathways. We focused on the putative
      targets of the SHH MB CSC miRNAs that were involved in the enriched pathways of
      interest, namely pathways in cancer, PI3k-Akt pathway and protein processing in
      endoplasmic reticulum pathway. In silico analysis was performed in SHH MB
      patients and identified several genes, whose expression was associated with worse
      overall survival of SHH MB patients. This study provides novel candidates whose
      functional role should be further investigated in SHH MB.

PMID- 30096800
TI  - Efficient Inkjet Printing of Graphene-Based Elements: Influence of Dispersing
      Agent on Ink Viscosity.
AB  - Inkjet printing is an excellent printing technique and an attractive alternative
      to conventional technologies for the production of flexible, low-cost
      microelectronic devices. Among many parameters that have a significant impact on
      the correctness of the printing process, the most important is ink viscosity.
      During the printing process, the ink is influenced by different strains and
      forces, which significantly change the printing results. The authors present a
      model and calculations referring to the shear rate of ink in an inkjet printer
      nozzle. Supporting experiments were conducted, proving the model assumptions for
      two different ink formulations: initial ink and with the addition of a dispersing
      agent. The most important findings are summarized by the process window regime of
      parameters, which is much broader for the inks with a dispersing agent. Such inks
      exhibit preferable viscosity, better print-ability, and higher path quality with
      lower resistivity. Presented results allow stating that proper, stable graphene
      inks adjusted for inkjet technique rheology must contain modifiers such as
      dispersing agents to be effectively printed.

PMID- 30096799
TI  - "My Tummy Tells Me" Cognitions, Barriers and Supports of Parents and School-Age
      Children for Appropriate Portion Sizes.
AB  - Larger portion sizes have increased in tandem with the rise in obesity.
      Elucidation of the cognitions of children and parents related to portion size is
      needed to inform the development of effective obesity prevention programs. This
      study examined cognitions of parents (n = 36) and their school-age children (6 to
      11 years; n = 35) related to portion sizes via focus group discussions. Parents
      and children believed controlling portion sizes promoted health and weight
      control. Some parents felt controlling portions was unnecessary, particularly if
      kids were a healthy weight because kids can self-regulate intake. Barriers to
      serving appropriate portions identified by parents focused largely on kids
      getting enough, rather than too much, to eat. Parents also identified lack of
      knowledge of age-appropriate portions as a barrier. Facilitators of portion
      control cited by parents included purchasing pre-portioned products and using
      small containers to serve food. Children relied on cues from parents (e.g.,
      amount of food parent served them) and internal hunger/satiety cues to regulate
      intake but found it difficult to avoid overeating highly palatable foods, at
      restaurants, and when others were overeating. Results suggest obesity prevention
      interventions should aim to improve portion sizes cognitions, barrier management,
      and use of facilitators, in families with school-age children.

PMID- 30096802
TI  - Distributed Deformation Monitoring for a Single-Cell Box Girder Based on
      Distributed Long-Gage Fiber Bragg Grating Sensors.
AB  - Distributed deformation based on fiber Bragg grating sensors or other kinds of
      strain sensors can be used to monitor bridges during operation. However, most
      research on distributed deformation monitoring has focused on solid rectangular
      beams rather than box girders-a kind of typical hollow beam widely employed in
      actual bridges. The deformation of a single-cell box girder contains bending
      deflection and also two additional deformations respectively caused by shear lag
      and shearing action. This paper revises the improved conjugated beam method
      (ICBM) based on the long-gage fiber Bragg grating (LFBG) sensors to satisfy the
      requirements for monitoring the two additional deformations in a single-cell box
      girder. This paper also proposes a suitable LFBG sensor placement in a box girder
      to overcome the influence of strain fluctuation on the flange caused by the shear
      lag effect. Results from numerical simulations show that the theoretical
      monitoring errors of the revised ICBM are typically 0.3-1.5%, and the maximum
      error is 2.4%. A loading experiment for a single-cell box gilder monitored by
      LFBG sensors shows that most of the practical monitoring errors are 6-8% and the
      maximum error is 11%.

PMID- 30096801
TI  - Developing Hollow-Channel Gold Nanoflowers as Trimodal Intracellular Nanoprobes.
AB  - Gold nanoparticles-enabled intracellular surface-enhanced Raman spectroscopy
      (SERS) provides a sensitive and promising technique for single cell analysis.
      Compared with spherical gold nanoparticles, gold nanoflowers, i.e., flower-shaped
      gold nanostructures, can produce a stronger SERS signal. Current exploration of
      gold nanoflowers for intracellular SERS has been considerably limited by the
      difficulties in preparation, as well as background signal and cytotoxicity
      arising from the surfactant capping layer. Recently, we have developed a facile
      and surfactant-free method for fabricating hollow-channel gold nanoflowers
      (HAuNFs) with great single-particle SERS activity. In this paper, we investigate
      the cellular uptake and cytotoxicity of our HAuNFs using a RAW 264.7 macrophage
      cell line, and have observed effective cellular internalization and low
      cytotoxicity. We have further engineered our HAuNFs into SERS-active tags, and
      demonstrated the functionality of the obtained tags as trimodal nanoprobes for
      dark-field and fluorescence microscopy imaging, together with intracellular SERS.

PMID- 30096803
TI  - Lactase Persistence, Milk Intake, and Adult Acne: A Mendelian Randomization Study
      of 20,416 Danish Adults.
AB  - Whether there is a causal relationship between milk intake and acne is unknown.
      We tested the hypothesis that genetically determined milk intake is associated
      with acne in adults using a Mendelian randomization design. LCT-13910 C/T
      (rs4988235) is associated with lactase persistence (TT/TC) in Northern Europeans.
      We investigated the association between milk intake, LCT-13910 C/T (rs4988235),
      and acne in 20,416 adults (age-range: 20-96) from The Danish General Suburban
      Population Study (GESUS). The adjusted observational odds ratio for acne in any
      milk intake vs. no milk intake was 0.93(95% confidence interval: 0.48-1.78) in
      females and 0.49(0.22-1.08) in males aged 20-39 years, and 1.15(95% confidence
      interval: 0.66-1.99) in females and 1.02(0.61-1.72) in males above 40 years. The
      unadjusted odds ratio for acne in TT+TC vs. CC was 0.84(0.43-1.62) in the age
      group 20-39 years, and 0.99(0.52-1.88) above 40 years. We did not find any
      observational or genetic association between milk intake and acne in our
      population of adults.

PMID- 30096804
TI  - Comparative Transcriptomic Analysis of Immune-Related Gene Expression in Duck
      Embryo Fibroblasts Following Duck Tembusu Virus Infection.
AB  - Duck is a major waterfowl species in China, providing high-economic benefit with
      a population of up to 20-30 billion per year. Ducks are commonly affected by
      severe diseases, including egg-drop syndrome caused by duck Tembusu virus
      (DTMUV). The immune mechanisms against DTMUV invasion and infection remain poorly
      understood. In this study, duck embryo fibroblasts (DEFs) were infected with
      DTMUV and harvested at 12 and 24 h post-infection (hpi), and their genomes were
      sequenced. In total, 911 (764 upregulated and 147 downregulated genes) and 3008
      (1791 upregulated and 1217 downregulated) differentially expressed genes (DEGs)
      were identified at 12 and 24 hpi, respectively. Kyoto Encyclopedia of Genes and
      Genomes enrichment analysis revealed that DEGs were considerably enriched in
      immune-relevant pathways, including Toll-like receptor signaling pathway,
      Cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway, Chemokine
      signaling pathway, NOD-like receptor signaling pathway, and Hematopoietic cell
      lineage at both time points. The key DEGs in immune system included those of the
      cytokines (IFN alpha2, IL-6, IL-8L, IL-12B, CCR7, CCL19, and CCL20),
      transcription factors or signaling molecules (IRF7, NF-kappaB, STAT1, TMEM173,
      and TNFAIP3), pattern recognition receptors (RIG-I and MDA5), and antigen
      presenting proteins (CD44 and CD70). This suggests DTMUV infection induces strong
      proinflammatory/antiviral effects with enormous production of cytokines. However,
      these cytokines could not protect DEFs against viral attack. Our data revealed
      valuable transcriptional information regarding DTMUV-infected DEFs, thereby
      broadening our understanding of the immune response against DTMUV infection; this
      information might contribute in developing strategies for controlling the
      prevalence of DTMUV infection.

PMID- 30096805
TI  - Pectolinarigenin Induced Cell Cycle Arrest, Autophagy, and Apoptosis in Gastric
      Cancer Cell via PI3K/AKT/mTOR Signaling Pathway.
AB  - Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and
      in some species of Citrus fruits, has various pharmacological benefits such as
      anti-inflammatory and anti-cancer activities. In the present study, we
      investigated the anti-cancer mechanism of PEC induced cell death caused by
      autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC
      treatment significantly inhibited the AGS and MKN28 cell growth in a dose
      dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells
      and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was
      confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover,
      Immunoblotting results revealed that PEC treatment down-regulated the inhibitor
      of apoptosis protein (IAP) family protein XIAP that leads to the activation of
      caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and
      MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was
      indicated by the increased formation of acidic vesicular organelles (AVOs) and
      increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC
      shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of
      autophagic and apoptotic cell death in cancer cells that leads to the down
      regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared
      with the untreated cells. In conclusion, PEC treatment might have anti-cancer
      effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell
      cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells.
      Further studies of PEC treatment can support to develop as a potential
      alternative therapeutic agent for human gastric carcinoma.

PMID- 30096806
TI  - Discovery of 4,5-Dihydro-1H-thieno[2',3':2,3]thiepino [4,5-c]pyrazole-3
      carboxamide Derivatives as the Potential Epidermal Growth Factor Receptors for
      Tyrosine Kinase Inhibitors.
AB  - The epidermal growth factor receptors (EGFRs), in which overexpression (known as
      upregulation) or overactivity have been associated with a number of cancers, has
      become an attractive molecular target for the treatment of selective cancers. We
      report here the design and synthesis of a novel series of 4,5-dihydro-1H-thieno
      [2',3':2,3]thiepino[4,5-c]pyrazole-3-carboxamide derivatives and the screening
      for their inhibitory activity on the EGFR high-expressing human A549 cell line
      using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). A
      Docking simulation was performed to fit compound 6g and gifitinib into the EGFR
      to determine the probable binding models, and the binding sites and modes
      conformation of 6g and gifitinib were exactly similar, the two compounds were
      stabilized by hydrogen bond interactions with MET769. Combining with the
      biological activity evaluation, compound 6g demonstrated the most potent
      inhibitory activity (IC50 = 9.68 +/- 1.95 MUmol.L-1 for A549). Conclusively, 4,5
      dihydro-1H-thieno[2',3':2,3]thiepino[4,5-c]pyrazole-3-carboxamide derivatives as
      the EGFR tyrosine kinase inhibitors were discovered, and could be used as
      potential lead compounds against cancer cells.

PMID- 30096807
TI  - Discovering Health Benefits of Phytochemicals with Integrated Analysis of the
      Molecular Network, Chemical Properties and Ethnopharmacological Evidence.
AB  - Identifying the health benefits of phytochemicals is an essential step in drug
      and functional food development. While many in vitro screening methods have been
      developed to identify the health effects of phytochemicals, there is still room
      for improvement because of high cost and low productivity. Therefore, researchers
      have alternatively proposed in silico methods, primarily based on three types of
      approaches; utilizing molecular, chemical or ethnopharmacological information.
      Although each approach has its own strength in analyzing the characteristics of
      phytochemicals, previous studies have not considered them all together. Here, we
      apply an integrated in silico analysis to identify the potential health benefits
      of phytochemicals based on molecular analysis and chemical properties as well as
      ethnopharmacological evidence. From the molecular analysis, we found an average
      of 415.6 health effects for 591 phytochemicals. We further investigated
      ethnopharmacological evidence of phytochemicals and found that on average 129.1
      (31%) of the predicted health effects had ethnopharmacological evidence. Lastly,
      we investigated chemical properties to confirm whether they are orally bio
      available, drug available or effective on certain tissues. The evaluation results
      indicate that the health effects can be predicted more accurately by
      cooperatively considering the molecular analysis, chemical properties and
      ethnopharmacological evidence.

PMID- 30096808
TI  - Human Papillomavirus-16 DNA Quantitation Differentiates High-Grade Anal
      Neoplasia.
AB  - Background: Due to their higher rates of anal dysplasia/cancer, human
      immunodeficiency virus (HIV)-positive individuals are recommended to undergo anal
      dysplasia screening, which consists of anal cytology (AC) and high resolution
      anoscopy (HRA) with anal biopsy (AB) after abnormal AC result. However, AC
      variability limits its usefulness. Our objective was to evaluate human
      papillomavirus (HPV)-16 DNA quantitation as part of the screening algorithm.
      Methods: HPV-16 was detected in AC specimens from 75 HIV-positive participants
      using quantitative real-time polymerase chain reaction. AB results were available
      from 18/44 patients who had abnormal AC. Statistical tests included Mann-Whitney
      U, Kruskal-Wallis, receiver operating characteristic (ROC) analysis and Kappa
      coefficient tests. Results: HPV-16 copy numbers differed significantly across AC
      (p = 0.001) and AB grades (p = 0.009). HPV-16 >= 65 copies/cell predicted high
      grade AB (p = 0.04). Using this cut-off in comparison to AB, it had better
      specificity (1.00) than AC (0.75) and specificity (0.77) than qualitative HPV-16
      detection (0.38). Also, the Kappa coefficient of the cut-off (kappa = 0.649) was
      higher than AC (kappa = 0.557) and qualitative HPV-16 detection (kappa = 0.258)
      to AB. Conclusion: Higher HPV-16 copy numbers corresponded to higher AC and AB
      grades, suggesting the importance of HPV burden on disease stage. Furthermore,
      HPV-16 >= 65 copies/cell distinguished high-grade disease and demonstrated better
      sensitivity, specificity, and agreement with AB than AC or qualitative HPV-16
      detection. These results support the potential use of HPV quantitation in
      conjunction with AC in anal dysplasia screening.

PMID- 30096809
TI  - The Value of Oxygenation Saturation Index in Predicting the Outcomes of Patients
      with Acute Respiratory Distress Syndrome.
AB  - This study aims to investigate the association between oxygenation saturation
      index (OSI) and the outcome of acute respiratory distress syndrome (ARDS)
      patients, and assess the predictive performance of OSI for ARDS patients'
      mortality. This study was conducted at one regional hospital with 66 adult
      intensive care unit (ICU) beds. All patients with ARDS were identified between
      November 1 2016 and May 31 2018, and their clinical information was
      retrospectively collected. The lowest PaO2/FiO2 ratio and SpO2/FiO2 ratio and
      highest mean airway pressure (MAP) were recorded on the first day of ARDS; and
      oxygen index (OI) and OSI were calculated as (FiO2 * MAP * 100)/PaO2, and (FiO2 *
      MAP * 100) /SpO2 accordingly. During the study period, a total of 101 patients
      with ARDS were enrolled, and their mean age was 69.2 years. The overall in-ICU
      and in-hospital mortality rate was 57.4% and 61.4%, respectively. The patients
      with in-ICU mortality had higher APACHE II score than the survivors (31.6 +/- 9.8
      vs. 23.0 +/- 9.1, p < 0.001). In addition, mortalities had lower SpO2, and
      SpO2/FiO2 ratios than the survivors (both p < 0.05). In contrast, survivors had
      lower OI, and OSI than the mortalities (both p = 0.008). Both OSI (area under
      curve (AUC) = 0.656, p = 0.008) and OI (AUC = 0.654, p = 0.008) had good
      predictive performance of mortality among ARDS patients using receiver-operating
      characteristics (ROC) curves analysis. In addition, the AUC of SpO2/FiO2 (AUC =
      0.616, p = 0.046) had better performance for mortality prediction than PaO2/FiO2
      (AUC = 0.603, p = 0.08). The patients with OSI greater than 12 had a higher risk
      of mortality than OSI < 12 (adjusted OR, 5.22, 95% CI, 1.31-20.76, p = 0.019). In
      contrast, OI, PaO2/FiO2, and SpO2/FiO2 were not found to be significantly
      associated with increased mortality. OSI is significantly associated with the
      increased mortality of ARDS patients and can also be a good outcome predictor.

PMID- 30096812
TI  - Effect of CaO on Phase Composition and Properties of Aluminates for Barium
      Tungsten Cathode.
AB  - 6BaO.xCaO.2Al2O3 (x = 0.8, 1.2, 1.6, 2, and 2.2) aluminates were synthesized via
      a liquid phase co-precipitation method. Effects of the molar amount of CaO on the
      phase of aluminates before and after melting and their hygroscopic phase, melting
      properties, environmental stability, evaporation, and emission properties were
      systematically studied. The results show that with the increase of the molar
      amount of CaO, the aluminates change from a mixture phase to a single phase of
      Ba3CaAl2O7, and the diffraction peak shifts to a higher angle. The melted phase
      of the aluminates changed from a single phase to a mixed phase of Ba5CaAl4O12 and
      Ba3CaAl2O7. Meanwhile, the comprehensive properties of the aluminates are
      improved. The weight gain of 6BaO.2CaO.2Al2O3 aluminates is only 10.88% after
      exposure to air for 48 h; the pulse emission current density of barium tungsten
      cathodes impregnated with 6BaO.2CaO.2Al2O3 aluminates in the porous tungsten
      matrix can reach 28.60 A/cm2 at 1050  degrees C, and the evaporation rate is 2.52
      * 10-10 g/(cm2.s).

PMID- 30096811
TI  - Real-World Implications of Nonbiological Factors with Staging, Prognosis and
      Clinical Management in Colon Cancer.
AB  - Background: The present study analyzed the nonbiological factors (NBFs) together
      with the American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM)
      staging system to generate a refined, risk-adapted stage for the clinical
      treatment of colon cancer. Methods: Eligible patients (N = 28,818) with colon
      cancer between 1 January 2010 and 31 December 2014, were identified from the
      Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier curves
      and Cox proportional hazards regression, analyzed the probabilities of cancer
      specific survival (CSS) in patients with colon cancer, with different NBF-TNM
      stages. Results: Insurance status, marital status, and median household income
      were significant prognostic NBFs in the current study (p < 0.05). The concordance
      index of NBF-TNM stage was 0.857 (95% confidence interval (CI) = 0.8472-0.8668).
      Multivariate Cox analyses, indicated that NBF1-stage was independently associated
      with a 50.4% increased risk of cancer-specific mortality in colon cancer (p <
      0.001), which increased to 77.1% in non-metastatic colon cancer. NBF0-stage
      improved in CSS as compared to the NBF1-stage in the respective stages (p <
      0.05). Conclusions: The new proposed NBF-stage was an independent prognostic
      factor in colon cancer. Effect of NBFs on the survival of colon cancer
      necessitates further clinical attention. Moreover, the incorporation of NBF-stage
      into the AJCC TNM staging system is essential for prognostic prediction, and
      clinical guidance of adjuvant chemotherapy in stage II and III colon cancer.

PMID- 30096810
TI  - Novel Configurations of Ultrahigh Frequency (<=600 MHz) Analog Frontend for High
      Resolution Ultrasound Measurement.
AB  - In this article, an approach to designing and developing an ultrahigh frequency
      (<=600 MHz) ultrasound analog frontend with Golay coded excitation sequence for
      high resolution imaging applications is presented. For the purpose of visualizing
      specific structures or measuring functional responses of micron-sized biological
      samples, a higher frequency ultrasound is needed to obtain a decent spatial
      resolution while it lowers the signal-to-noise ratio, the difference in decibels
      between the signal level and the background noise level, due to the higher
      attenuation coefficient. In order to enhance the signal-to-noise ratio,
      conventional approach was to increase the transmit voltage level. However, it may
      cause damaging the extremely thin piezoelectric material in the ultrahigh
      frequency range. In this paper, we present a novel design of ultrahigh frequency
      (<=600 MHz) frontend system capable of performing pseudo Golay coded excitation
      by configuring four independently operating pulse generators in parallel and the
      consecutive delayed transmission from each channel. Compared with the
      conventional monocycle pulse approach, the signal-to-noise ratio of the proposed
      approach was improved by 7-9 dB without compromising the spatial resolution. The
      measured axial and lateral resolutions of wire targets were 16.4 um and 10.6 um
      by using 156 MHz 4 bit pseudo Golay coded excitation, respectively and 4.5 um and
      7.7 um by using 312 MHz 4 bit pseudo Golay coded excitation, respectively.

PMID- 30096813
TI  - CEP55 Promotes Cell Motility via JAK2-STAT3-MMPs Cascade in Hepatocellular
      Carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies and has a
      poor prognosis. Novel diagnostic or prognostic biomarkers and potential
      therapeutic targets for HCC are thus urgently needed. CEP55 plays a crucial role
      in regulating physical cytokinesis. Whether, and how, CEP55 contributes to HCC
      development remains unclear. Herein, we demonstrate that CEP55 is abnormally
      upregulated in HCC tissue, and these high levels of CEP55 are closely related to
      the poor prognosis of HCC patients. Knockdown of CEP55 expression significantly
      inhibits HCC cell migration and invasion. We also demonstrate that CEP55
      physiologically interacts with JAK2 and promotes its phosphorylation; thus, it is
      a novel regulator of JAK2-STAT3 signaling and its target genes MMP2/9. Finally,
      blocking JAK2 or STAT3 blunts the stimulation of migration and invasion due to
      CEP55 overexpression. In summary, our results suggest that CEP55, as an oncogene,
      promotes HCC cell migration and invasion through regulating JAK2-STAT3-MMPs
      signaling.

PMID- 30096815
TI  - Energy-Aware Control of Error Correction Rate for Solar-Powered Wireless Sensor
      Networks.
AB  - In a wireless sensor network (WSN) environment with frequent errors, forward
      error correction (FEC) is usually employed at the link layer to achieve reliable
      transmission. In the FEC scheme, the error correction rate varies depending on
      the length of parity used for the recovery of broken data. The longer the parity
      length, the higher the possible error correction rate. However, this also means
      that the energy consumption increases. Meanwhile, in a solar-powered WSN, the
      energy of each node can be periodically collected, but the amount of collected
      energy varies drastically depending on the harvesting environment, including
      factors such as the weather, season and time of day. Therefore, each node must
      control energy consumption according to the energy harvesting rate. The scheme
      proposed in this study executes this control by adaptively adjusting the parity
      length of FEC according to the given energy budget of a node for the next period.
      This means that the error recovery rate can be increased as much as possible
      without adversely affecting the blackout time. Simulation results show that the
      proposed scheme improves the amount of data collected from the entire network for
      each environment compared with previous schemes.

PMID- 30096816
TI  - Evolution of Landscape Ecological Risk at the Optimal Scale: A Case Study of the
      Open Coastal Wetlands in Jiangsu, China.
AB  - Detailed analysis of the evolution characteristics of landscape ecological risk
      is crucial for coastal sustainable management and for understanding the potential
      environmental impacts of a man-made landform landscapes (MMLL). As a typical open
      coastal wetland, large-scale human activities (e.g., tidal reclamation, fishery
      activities, wind farm construction, and port construction) have substantially
      affected the evolution of the coastal ecological environment. Previous landscape
      ecological risk assessment studies have documented the effectiveness of assessing
      the quality of ecological environment processes. However, these studies have
      either focused on the noncoastal zone, or they have not considered the evolution
      of the spatial characteristics and ecological risk evolution of the landscape at
      an optimal scale. Here, we present a landscape ecological risk pattern (LERP)
      evolution model, based on two successive steps: first, we constructed an optimal
      scale method with an appropriate extent and grain using multi-temporal Landsat
      TM/OLI images acquired in the years 2000, 2004, 2008, 2013 and 2017, and then we
      calculated landscape ecological risk indices. Based on this model, the entire
      process of the spatiotemporal evolution of ecological risk patterns of the open
      coastal wetlands in Jiangsu, China, was determined. The principal findings are as
      follows: (1) The main landscape types in the study area are tidal flats and
      farmland, and the main features of the landscape evolution are a significant
      increase in aquafarming and a substantial decrease in the tidal flat area, while
      the landscape heterogeneity increased; (2) In the past 20 years, the areas of low
      and relatively low ecological risk in the study region were greatly reduced,
      while the areas of medium, relatively high, and high ecological risk greatly
      increased; the areas of high-grade ecological risk areas are mainly around
      Dongtai and Dafeng; (3) The area of ecological risk from low-grade to high-grade
      occupied 71.75% of the study area during 2000-2017. During the previous periods
      (2000-2004 and 2004-2008), the areas of low-grade ecological risk were
      transformed to areas of middle-grade ecological risk area, while during the later
      periods (2008-2013 and 2013-2017) there was a substantial increase in the
      proportion of areas of high-grade ecological risk. Our results complement the
      official database of coastal landscape planning, and provide important
      information for assessing the potential effects of MMLL processes on coastal
      environments.

PMID- 30096814
TI  - Predicting MicroRNA Mediated Gene Regulation between Human and Viruses.
AB  - MicroRNAs (miRNAs) mediate various biological processes by actively fine-tuning
      gene expression at the post-transcriptional level. With the identification of
      numerous human and viral miRNAs, growing evidence has indicated a common role of
      miRNAs in mediating the interactions between humans and viruses. However, there
      is only limited information about Cross-Kingdom miRNA target sites from studies.
      To facilitate an extensive investigation on the interplay among the gene
      regulatory networks of humans and viruses, we designed a prediction pipeline,
      mirTarP, that is suitable for miRNA target screening on the genome scale. By
      applying mirTarP, we constructed the database mirTar, which is a comprehensive
      miRNA target repository of bidirectional interspecies regulation between viruses
      and humans. To provide convenient downloading for users from both the molecular
      biology field and medical field, mirTar classifies viruses according to "ICTV
      viral category" and the "medical microbiology classification" on the web page.
      The mirTar database and mirTarP tool are freely available online.

PMID- 30096817
TI  - Mexican Households' Purchases of Foods and Beverages Vary by Store-Type, Taxation
      Status, and SES.
AB  - Where people shop for food is often linked to the healthiness of food purchases.
      In Mexico, no research has examined the connection between where people shop,
      what they buy, and their socioeconomic status (SES). Mexico's sugary beverage and
      junk food taxes have made households decrease purchases of taxed products.
      However, whether households have changed where they shop is unknown. To address
      this gap, we use a repeated cross-sectional analysis of household packaged food
      and beverage purchases from the Nielsen Mexico Consumer Panel Survey from 2012 to
      2015 (n > 5500 households). We examine changes in the volume of the purchase of
      taxed and untaxed products from different store-types (i.e., convenience stores,
      supermarkets, traditional retailers, wholesalers, home water-delivery, and
      others) by SES using multivariate linear regression models. Results show that
      high-SES households purchased more foods and beverages at all store-types except
      for low-SES who purchased the most foods and taxed beverages at traditional
      retailers. Purchases of taxed foods and beverages from traditional retailers
      significantly decreased for low-SES and middle-SES households and from
      supermarkets for middle-SES and high-SES households. Purchases of untaxed
      beverages from wholesalers significantly increased for middle-SES households and
      from convenience stores for high-SES households. Our findings suggest that
      consumers choose different stores to purchase beverages than to purchase foods
      and that taxes may have differentially affected each store-type.

PMID- 30096818
TI  - Reducing Humidity Response of Gas Sensors for Medical Applications: Use of Spark
      Discharge Synthesis of Metal Oxide Nanoparticles.
AB  - The application of gas sensors in breath analysis is an important trend in the
      early diagnostics of different diseases including lung cancer, ulcers, and
      enteric infection. However, traditional methods of synthesis of metal oxide gas
      sensing materials for semiconductor sensors based on wet sol-gel processes give
      relatively high sensitivity of the gas sensor to changing humidity. The sol-gel
      process leading to the formation of superficial hydroxyl groups on oxide
      particles is responsible for the strong response of the sensing material to this
      factor. In our work, we investigated the possibility to synthesize metal oxide
      materials with reduced sensitivity to water vapors. Dry synthesis of SnO2
      nanoparticles was implemented in gas phase by spark discharge, enabling the
      reduction of the hydroxyl concentration on the surface and allowing the
      production of tin dioxide powder with specific surface area of about 40 m2/g
      after annealing at 610  degrees C. The drop in sensor resistance does not exceed
      20% when air humidity increases from 40 to 100%, whereas the response to 100 ppm
      of hydrogen is a factor of 8 with very short response time of about 1 s. The
      sensor response was tested in mixtures of air with hydrogen, which is the marker
      of enteric infections and the marker of early stage fire, and in a mixture of air
      with lactate (marker of stomach cancer) and ammonia gas (marker of Helicobacter
      pylori, responsible for stomach ulcers).

PMID- 30096820
TI  - Corrosion Behavior and Mechanism of Basalt Fibers in Sodium Hydroxide Solution.
AB  - In this paper, the corrosion mechanism and tensile properties of basalt fibers in
      sodium hydroxide (NaOH) solution with various concentrations and temperatures
      were studied. The hydroxyl ions disrupt the -Si-O-Si- and -Si-O-Al- bonds leading
      to the formation of insoluble hydroxides. With the continuation of the hydration
      reaction, a hydration layer (corrosion shell) with high content of calcium, iron,
      manganese and titanium ions was formed on the fiber surface. The corrosion shell
      enabled an increase in the strength and elongation at break of basalt fibers,
      significantly. Results showed that the tensile strength of fibers was strongly
      dependent on temperature and concentration. After the basalt fibers were immersed
      in 1 mol/L NaOH solution at 50  degrees C for 1 h, 3 h, 6 h, 1 day and 3 days,
      their retention ratios of strength were 67.6%, 57.8%, 52.5%, 49.0%, 58.2%,
      respectively. Higher temperature accelerated the corrosion rate of basalt fibers,
      shortened the formation time of the corrosion shell and increased mass loss. From
      25 to 70  degrees C, the mass loss of fibers increased from 2.4% to 33.8% for
      fibers immersed in 1 mol/L NaOH for 3 days. The experimental results from
      quantitative x-ray fluorescence (XRF) showed that the mass loss of basalt fibers
      was mainly due to the leaching of silicon, aluminum and potassium ions.

PMID- 30096819
TI  - A Proteomic Approach to Uncover Neuroprotective Mechanisms of Oleocanthal against
      Oxidative Stress.
AB  - Neurodegenerative diseases represent a heterogeneous group of disorders that
      share common features like abnormal protein aggregation, perturbed Ca2+
      homeostasis, excitotoxicity, impairment of mitochondrial functions, apoptosis,
      inflammation, and oxidative stress. Despite recent advances in the research of
      biomarkers, early diagnosis, and pharmacotherapy, there are no treatments that
      can halt the progression of these age-associated neurodegenerative diseases.
      Numerous epidemiological studies indicate that long-term intake of a
      Mediterranean diet, characterized by a high consumption of extra virgin olive
      oil, correlates with better cognition in aged populations. Olive oil phenolic
      compounds have been demonstrated to have different biological activities like
      antioxidant, antithrombotic, and anti-inflammatory activities. Oleocanthal, a
      phenolic component of extra virgin olive oil, is getting more and more scientific
      attention due to its interesting biological activities. The aim of this research
      was to characterize the neuroprotective effects of oleocanthal against H2O2
      induced oxidative stress in neuron-like SH-SY5Y cells. Moreover, protein
      expression profiling, combined with pathways analyses, was used to investigate
      the molecular events related to the protective effects. Oleocanthal was
      demonstrated to counteract oxidative stress, increasing cell viability, reducing
      reactive oxygen species (ROS) production, and increasing reduced glutathione
      (GSH) intracellular level. Proteomic analysis revealed that oleocanthal
      significantly modulates 19 proteins in the presence of H2O2. In particular,
      oleocanthal up-regulated proteins related to the proteasome, the chaperone heat
      shock protein 90, the glycolytic enzyme pyruvate kinase, and the antioxidant
      enzyme peroxiredoxin 1. Moreover, oleocanthal protection seems to be mediated by
      Akt activation. These data offer new insights into the molecular mechanisms
      behind oleocanthal protection against oxidative stress.

PMID- 30096822
TI  - An Evaluation of Graphene Oxides as Possible Foam Stabilizing Agents for CO2
      Based Enhanced Oil Recovery.
AB  - Graphene oxide, nanographene oxide and partially reduced graphene oxide have been
      studied as possible foam stabilizing agents for CO2 based enhanced oil recovery.
      Graphene oxide was able to stabilize CO2/synthetic sea water foams, while
      nanographene oxide and partially reduced graphene oxide were not able to
      stabilize foams. The inability of nanographene oxide for stabilizing foams was
      explained by the increase of hydrophilicity due to size decrease, while for
      partially reduced graphene oxide, the high degree of reduction of the material
      was considered to be the reason. Graphene oxide brine dispersions showed
      immediate gel formation, which improved foam stability. Particle growth due to
      layer stacking was also observed. This mechanism was detrimental for foam
      stabilization. Gel formation and particle growth caused these particles to block
      pores and not being filterable. The work indicates that the particles studied are
      not suitable for CO2 enhanced oil recovery purposes.

PMID- 30096821
TI  - Macronutrient Composition of the Australian Population's Diet; Trends from Three
      National Nutrition Surveys 1983, 1995 and 2012.
AB  - Although the role of individual macronutrients in the development of obesity
      remains controversial, changes in macronutrient composition of the diet may have
      played a causal role in the obesity epidemic. The aim of this analysis was to
      determine the percentage energy (%E) for protein, carbohydrate and fat of
      Australian adults' diets over time. Cross-sectional, national nutrition surveys
      from 1983, 1995 and 2012 assessed diet using one 24 h recall. The prevalence of
      obesity increased between each survey, from 9.6% to 19.7% and 27.7%. Protein (%E)
      differed between each survey and contributed 17.7%, 16.8% and 18.3% energy in
      1983, 1995 and 2012, respectively (p < 0.001). Carbohydrate (%E) increased from
      40.0% in 1983 to 44.9% in 1995 (p < 0.001), with no change in dietary fibre but
      declined in 2012 to 43.1%. Fat (%E) declined between each survey from 35.3%,
      31.9%, to 30.9%, respectively (p < 0.001). Alcohol (%E) has declined for younger
      adults and men but intake increased for women aged >45 years. Prospective cohort
      studies with comprehensive assessment of foods consumed, together with
      measurements of weight and height, will advance the understanding of the
      relationship between macronutrients and changes in body weight and obesity.

PMID- 30096823
TI  - What People Want to Know About Their Genes: A Critical Review of the Literature
      on Large-Scale Genome Sequencing Studies.
AB  - From a public health perspective, the "All of Us" study provides an opportunity
      to isolate targeted and cost-effective prevention and early-detection strategies.
      Identifying motivations for participation in large-scale genomic sequencing
      (LSGS) studies, and motivations and preferences to receive results will help
      determine effective strategies for "All of Us" study implementation. This paper
      offers a critical review of the literature regarding LSGS for adult onset
      hereditary conditions where results could indicate an increased risk to develop
      disease. The purpose of this review is to synthesize studies which explored
      peoples' motivations for participating in LSGS studies, and their desire to
      receive different types of genetic results. Participants were primarily motivated
      by altruism, desire to know more about their health, and curiosity. When asked
      about hypothetically receiving results, most participants in hypothetical studies
      wanted all results except those which were uncertain (i.e., a variant of
      uncertain significance (VUS)). However, participants in studies where results
      were returned preferred to receive only results for which an intervention was
      available, but also wanted VUS. Concerns about peoples' understanding of results
      and possible psychosocial implications are noted. Most studies examined
      populations classified as "early adopters," therefore, additional research on
      motivations and expectations among the general public, minority, and underserved
      populations is needed.

PMID- 30096825
TI  - Lifetime Prediction of Polymers: To Bet, or Not to Bet-Is This the Question?
AB  - Polymers are a great and very important category of organic compounds that have
      changed our lifestyle. In the last eighty years, we have used them for the most
      varied applications, and from the first structural ones we began to investigate
      their durability, which can be fatal in the successful completion of the
      application for which the material was designed. Over the last thirty years, the
      environmental problems related to the disposal of polymers that have completed
      their lifecycle have begun to arise, and the need to foresee their end of life
      has become increasingly urgent. In this manuscript, the reliability of the
      lifetime predictions of polymeric materials is faced with comparing measurements
      obtained at low temperature with those carried out at high temperatures, in the
      molten state. The obtained data were treated by a well-established kinetics model
      and discrepancies were observed in the two different conditions (high and low
      temperatures), which led to a mismatching between expected and real data. A
      correction of the data extrapolated from measurements obtained at high
      temperatures, by using a novel equation which takes into account the induction
      period (IP) of the degradation process, is proposed. Considerations about the
      useful parameters, namely initial decomposition temperature (Ti), activation
      energy of degradation (Ea), and glass-transition temperature (Tg), to be used for
      making predictions, are also carried out.

PMID- 30096826
TI  - Surface Quality Enhancement of Fused Deposition Modeling (FDM) Printed Samples
      Based on the Selection of Critical Printing Parameters.
AB  - The present paper shows an experimental study on additive manufacturing for
      obtaining samples of polylactic acid (PLA). The process used for manufacturing
      these samples was fused deposition modeling (FDM). Little attention to the
      surface quality obtained in additive manufacturing processes has been paid by the
      research community. So, this paper aims at filling this gap. The goal of the
      study is the recognition of critical factors in FDM processes for reducing
      surface roughness. Two different types of experiments were carried out to analyze
      five printing parameters. The results were analyzed by means of Analysis of
      Variance, graphical methods, and non-parametric tests using Spearman's rho and
      Kendall's tau correlation coefficients. The results showed how layer height and
      wall thickness are the most important factors for controlling surface roughness,
      while printing path, printing speed, and temperature showed no clear influence on
      surface roughness.

PMID- 30096824
TI  - Revisiting Centrioles in Nematodes-Historic Findings and Current Topics.
AB  - Theodor Boveri is considered as the "father" of centrosome biology. Boveri's
      fundamental findings have laid the groundwork for decades of research on
      centrosomes. Here, we briefly review his early work on centrosomes and his first
      description of the centriole. Mainly focusing on centriole structure,
      duplication, and centriole assembly factors in C. elegans, we will highlight the
      role of this model in studying germ line centrosomes in nematodes. Last but not
      least, we will point to future directions of the C. elegans centrosome field.

PMID- 30096828
TI  - Ga-Based Alloys in Microelectronic Interconnects: A Review.
AB  - Gallium (Ga) and some of its alloys have a range of properties that make them an
      attractive option for microelectronic interconnects, including low melting point,
      non-toxicity, and the ability to wet without fluxing most materials-including
      oxides-found in microelectronics. Some of these properties result from their
      ability to form stable high melting temperature solid solutions and intermetallic
      compounds with other metals, such as copper, nickel, and aluminium. Ga and Ga
      based alloys have already received significant attention in the scientific
      literature given their potential for use in the liquid state. Their potential for
      enabling the miniaturisation and deformability of microelectronic devices has
      also been demonstrated. The low process temperatures, made possible by their low
      melting points, produce significant energy savings. However, there are still some
      issues that need to be addressed before their potential can be fully realised.
      Characterising Ga and Ga-based alloys, and their reactions with materials
      commonly used in the microelectronic industry, are thus a priority for the
      electronics industry. This review provides a summary of research related to the
      applications and characterisation of Ga-based alloys. If the potential of Ga
      based alloys for low temperature bonding in microelectronics manufacturing is to
      be realised, more work needs to be done on their interactions with the wide range
      of substrate materials now being used in electronic circuitry.

PMID- 30096827
TI  - Chrysin Ameliorates Malfunction of Retinoid Visual Cycle through Blocking
      Activation of AGE-RAGE-ER Stress in Glucose-Stimulated Retinal Pigment Epithelial
      Cells and Diabetic Eyes.
AB  - Diabetes-associated visual cycle impairment has been implicated in diabetic
      retinopathy, and chronic hyperglycemia causes detrimental effects on visual
      function. Chrysin, a naturally occurring flavonoid found in various herbs, has
      anti-inflammatory, antioxidant, and neuroprotective properties. The goal of the
      current study was to identify the retinoprotective role of chrysin in maintaining
      robust retinoid visual cycle-related components. The in vitro study employed
      human retinal pigment epithelial (RPE) cells exposed to 33 mM of glucose or
      advanced glycation end products (AGEs) in the presence of 1-20 MUM chrysin for
      three days. In the in vivo study, 10 mg/kg of chrysin was orally administrated to
      db/db mice. Treating chrysin reversed the glucose-induced production of vascular
      endothelial growth factor, insulin-like growth factor-1, and pigment epithelium
      derived factor (PEDF) in RPE cells. The outer nuclear layer thickness of chrysin
      exposed retina was enhanced. The oral gavage of chrysin augmented the levels of
      the visual cycle enzymes of RPE65, lecithin retinol acyltransferase (LRAT),
      retinol dehydrogenase 5 (RDH5), and rhodopsin diminished in db/db mouse retina.
      The diabetic tissue levels of the retinoid binding proteins and the receptor of
      the cellular retinol-binding protein, cellular retinaldehyde-binding protein-1,
      interphotoreceptor retinoid-binding protein and stimulated by retinoic acid 6
      were restored to those of normal mouse retina. The presence of chrysin demoted
      AGE secretion and AGE receptor (RAGE) induction in glucose-exposed RPE cells and
      diabetic eyes. Chrysin inhibited the reduction of PEDF, RPE 65, LRAT, and RDH5 in
      100 MUg/mL of AGE-bovine serum albumin-exposed RPE cells. The treatment of RPE
      cells with chrysin reduced the activation of endoplasmic reticulum (ER) stress.
      Chrysin inhibited the impairment of the retinoid visual cycle through blocking ER
      stress via the AGE-RAGE activation in glucose-stimulated RPE cells and diabetic
      eyes. This is the first study demonstrating the protective effects of chrysin on
      the diabetes-associated malfunctioned visual cycle.

PMID- 30096829
TI  - The DPSIR Model for Environmental Risk Assessment of Municipal Solid Waste in Dar
      es Salaam City, Tanzania.
AB  - Environmental risk has become an area of major concern and research, drawing
      special attention. This study on the environmental risk assessment (ERA) of Dar
      es Salaam Municipal Solid Waste comes at a time when the Government of Tanzania
      is becoming increasingly concerned about dealing with high levels of pollution
      from municipal solid waste (MSW). The paper employed the Driving force-Pressure
      State-Impact-Response (DPSIR) model to establish an environmental risk indicator
      system and the analytical hierarchy process (AHP) to calculate and analyze risk
      values, based on the actual situation of MSW in the city of Dar es Salaam. It
      lists several measures that have been taken in response to the current
      significantly high levels of pollution, which have assisted in maintaining the
      environmental risk index (ERI) at a medium level (0.4-0.6) during the period from
      2006-2017. However, these measures have not been adequate enough to manage the
      external pressure. The ERI has been increasing gradually, calling for timely
      formulation of demand-specific waste management policies to reduce the
      possibility of reaching the critical point in near future. With the use of the
      DPSIR model for ERA, this study has become highly valuable, providing empirical
      justification to reduce environmental risk from MSW, which is one of the main
      sources of environmental pollution in the urban areas of developing countries.

PMID- 30096830
TI  - Inclusion and Exclusion Criteria of Clinical Trials for Insomnia.
AB  - Randomized controlled trials (RCTs) have eligibility criteria for the inclusion
      of participants. Ideally, the RCT sample would be representative for the patient
      population that will use the drug under investigation. However, external validity
      may be at stake when applying too many or too restrictive eligibility criteria.
      The current two-part study examined (1) the currently applied eligibility
      criteria in Phase II and III RCTs examining sleep medication; (2) how these
      criteria match with the insomnia population as a whole; and (3) how inclusion
      rates can be changed by an adaptation of these criteria. In the first study,
      insomnia RCTs were screened at www.clinicaltrials.gov, and relevant eligibility
      criteria were identified. The second study comprised a survey among self-reported
      insomnia patients. It was determined to what extent RCT eligibility criteria
      match the characteristics of this patient population. Of the n = 519 patients
      that completed the survey only n = 2 (0.4%) met all eligibility criteria of
      current RCTs. RCT enrolment criteria are not representative for the insomnia
      patient population as a whole. Being less rigorous in applying upper or lower
      criteria limits results in a significant increase in the number of eligible
      patients, and increases the representativeness of RCTs for the insomnia patient
      population as a whole. The current analysis demonstrates that is important to
      thoroughly reconsider the use eligibility criteria and their inclusion ranges,
      and to have a theoretical basis for using them.

PMID- 30096832
TI  - Deep Learning-Based Enhanced Presentation Attack Detection for Iris Recognition
      by Combining Features from Local and Global Regions Based on NIR Camera Sensor.
AB  - Iris recognition systems have been used in high-security-level applications
      because of their high recognition rate and the distinctiveness of iris patterns.
      However, as reported by recent studies, an iris recognition system can be fooled
      by the use of artificial iris patterns and lead to a reduction in its security
      level. The accuracies of previous presentation attack detection research are
      limited because they used only features extracted from global iris region image.
      To overcome this problem, we propose a new presentation attack detection method
      for iris recognition by combining features extracted from both local and global
      iris regions, using convolutional neural networks and support vector machines
      based on a near-infrared (NIR) light camera sensor. The detection results using
      each kind of image features are fused, based on two fusion methods of feature
      level and score level to enhance the detection ability of each kind of image
      features. Through extensive experiments using two popular public datasets (LivDet
      Iris-2017 Warsaw and Notre Dame Contact Lens Detection 2015) and their fusion, we
      validate the efficiency of our proposed method by providing smaller detection
      errors than those produced by previous studies.

PMID- 30096831
TI  - A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the
      Determination of Nimbolide in Mouse Serum: Application to a Preclinical
      Pharmacokinetics Study.
AB  - A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS)
      method was developed and validated for the determination of nimbolide in mouse
      serum. Exemestane was used as the internal standard (IS). Here, we employed
      acetonitrile-based protein precipitation (PPT) for serum sample preparation, and
      performed chromatographic separation using an ODS Hypersil C18 column (100 mm *
      2.1 mm, 5 um) with gradient elution (0.1% formic acid in water vs 100%
      acetonitrile). The run time was 6 min. Instrumental analysis was performed by
      electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple
      reaction monitoring (MRM) under positive mode. A good linear calibration was
      achieved in the 5-1000 ng/mL range. The intra- and inter-day precisions for
      nimbolide were <=12.6% and <=13.9% respectively. Intra-day accuracy ranged from
      96.9-109.3%, while inter-day accuracy ranged from 94.3-110.2%. The matrix effect
      of nimbolide, detected but consistent at low and high concentrations, do not
      affect linearity of standard curve. In conclusion, we have developed and
      validated a sensitive analytical method for determination of a novel natural
      compound nimbolide in mouse serum, and it has been successfully applied to our
      preclinical study in investigating the pharmacokinetic properties of nimbolide,
      which could greatly facilitate the preclinical development of the promising lead
      compound for anticancer therapy.

PMID- 30096833
TI  - Pharmacokinetics, Tissue Distribution and Excretion of a Novel Diuretic (PU-48)
      in Rats.
AB  - Methyl 3-amino-6-methoxythieno [2,3-b] quinoline-2-carboxylate (PU-48) is a novel
      diuretic urea transporter inhibitor. The aim of this study is to investigate the
      profile of plasma pharmacokinetics, tissue distribution, and excretion by oral
      dosing of PU-48 in rats. Concentrations of PU-48 within biological samples are
      determined using a validated high performance liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method. After oral administration of PU-48 (3, 6, and 12
      mg/kg, respectively) in self-nanomicroemulsifying drug delivery system (SNEDDS)
      formulation, the peak plasma concentrations (Cmax), and the area under the curve
      (AUC0-infinity) were increased by the dose-dependent and linear manner, but the
      marked different of plasma half-life (t1/2) were not observed. This suggests that
      the pharmacokinetic profile of PU-48 prototype was first-order elimination
      kinetic characteristics within the oral three doses range in rat plasma.
      Moreover, the prototype of PU-48 was rapidly and extensively distributed into
      thirteen tissues, especially higher concentrations were detected in stomach,
      intestine, liver, kidney, and bladder. The total accumulative excretion of PU-48
      in the urine, feces, and bile was less than 2%. This research is the first report
      on disposition via oral administration of PU-48 in rats, and it provides
      important information for further development of PU-48 as a diuretic drug
      candidate.

PMID- 30096834
TI  - In Vitro Stimulation of Multidrug Resistance-Associated Protein 2 Function Is Not
      Reproduced In Vivo in Rats.
AB  - Previously we reported that coproporphyrin-I (CP-I) is an optimal probe substrate
      for multidrug resistance-associated protein 2 (MRP2), and stimulation of MRP2
      mediated transport is probe substrate-dependent. In the present investigation, we
      assessed if the in vitro stimulation is physiologically relevant. Similar to
      human MRP2 transport, CP-I was transported by rat Mrp2 in a typical Michaelis
      Menten kinetics with apparent Km and Vmax values of 15 +/- 6 uM and 161 +/- 20
      pmol/min/mg protein, respectively. In vivo Mrp2 functions were monitored by
      biliary and renal secretion of CP-I and its isomer CP-III, in bile-duct
      cannulated rats before and after treatment with mitoxantrone, progesterone, and
      verapamil. These compounds stimulated Mrp2-mediated CP-I transport in vitro. No
      significant increase in biliary or renal clearances, as well as in the cumulative
      amount of CP-I or CP-III eliminated in bile, were detected following treatment
      with the in vitro stimulators, indicating an in vitro to in vivo disconnect. In
      presence of 10 uM bilirubin, the in vitro stimulation was suppressed. We
      concluded that the in vitro stimulation of CP-I transport mediated by Mrp2 is not
      translatable in vivo, and proposed that the presence of endogenous compounds such
      as bilirubin in the liver may contribute to the in vitro to in vivo disconnect.

PMID- 30096835
TI  - New 2-Oxoindolin Phosphonates as Novel Agents to Treat Cancer: A Green Synthesis
      and Molecular Modeling.
AB  - The work reports the facile synthesis of novel alpha-aminophosphonate derivatives
      coupled with indole-2,3-dione moieties, namely the diethyl(substituted
      phenyl/heteroaryl)(2-(2-oxoindolin-3-ylidene)hydrazinyl)methylphosphonates
      derivatives 4(a-n). One-pot three component Kabachnik-Fields reactions were used
      to synthesize these derivatives. The reaction was carried out at room temperature
      by stirring in presence of ceric ammonium nitrate (CAN) as a green catalyst. The
      structures of the synthesized compounds were established by spectral studies. The
      synthesized derivatives 4(a-n) were evaluated for their in vitro anticancer
      activity against six human cancer cell lines by the SRB assay method. The cancer
      cell lines used in this research work are SK-MEL-2 (melanoma), MCF-7 (breast
      cancer), IMR-32 (neuroblastoma) MG-63 (human osteosarcoma), HT-29 (human colon
      cancer) and Hep-G2 (human hepatoma). All the synthesized derivatives inhibited
      the cell proliferation. Importantly, all the target compounds showed no
      cytotoxicity towards normal tissue cells (GI50 > 250 uM). A docking study was
      performed to predict the mode of action. Docking results indicate that the
      compounds have good binding with the enzyme tyrosine kinase as well as with
      microtubules, which makes them dual inhibitors. The result of in-silico
      bioavailability studies suggests that the compounds from the present series have
      good oral drug-like properties and are non-toxic in nature. In vivo acute oral
      toxicity study results indicate that the compounds can be considered safe, and
      therefore could be developed in the future as good anticancer agents or as leads
      for the design and synthesis of novel anticancer agents.

PMID- 30096836
TI  - A Study on Preparation and Stabilizing Mechanism of Hydrophobic Silica
      Nanofluids.
AB  - Nanofluids have increasingly drawn interest in recent years with their various
      applications in a number of fields. The method for the preparation of stable
      nanofluids is a key concern for extending the application of nanofluids. This
      study focuses on the effect of pH, dosage of surfactant (TX-100), and nanofluid
      concentration on the stability of a silica nanofluid. Particle size and zeta
      potential are two important factors to consider in evaluating the stability of
      the silica nanofluid. Results indicate that the stability of the silica nanofluid
      highly depends on pH, dosage of surfactant (TX-100), and nanofluid concentration.
      On the basis of these experiments, the best conditions for the preparation of a
      silica nanofluid are 0.1 wt. % for the concentration of silica nanoparticles and
      TX-100 and 10 for pH. A transparent and stable silica nanofluid can thus be
      obtained.

PMID- 30096837
TI  - Interactions between Mycorrhizal Fungi, Tea Wastes, and Algal Biomass Affecting
      the Microbial Community, Soil Structure, and Alleviating of Salinity Stress in
      Corn Yield (Zeamays L.).
AB  - Soil salinity has an adverse impact on soil biological properties and growth of
      corn plant, majorly in arid and semi-arid lands. A mesocosm experiment was
      conducted to investigate the effect of mycorrhizal fungi (M) (Glomus mosseae),
      tea wastes (T), algal dried biomass (A), and their combinations on soil
      respiration, total bacteria, total fungi, soil mean weight diameter (MWD), and
      corn yield (Zeamays L.). under saline and non-saline soils. Results showed that
      M, T, and A treatments increased significantly CO2 release compared to the
      control. Whereas, M significantly decreased CO2 release compared to T and A
      treatments. In non-saline soil, M increased greatly MWD, bacterial and fungal
      counts, and infection rate. Whereas, the opposite was true in the saline soil;
      neither M nor T improved bacterial communities and MWD. However, in the saline
      soil, M + T was highly efficient in improving MWD, SOC, bacterial and fungal
      counts, infection rate, and corn grain yield. It can be suggested that the
      inoculation of mycorrhizal fungi with tea wastes in saline soils considered an
      important strategy that increases the toleration of the corn plant to salinity by
      improving soil microbial activity, MWD, SOC, infection rate, and total grain
      yield.

PMID- 30096838
TI  - The SUMO System and TGFbeta Signaling Interplay in Regulation of Epithelial
      Mesenchymal Transition: Implications for Cancer Progression.
AB  - Protein post-translational modification by the small ubiquitin-like modifier
      (SUMO), or SUMOylation, can regulate the stability, subcellular localization or
      interactome of a protein substrate with key consequences for cellular processes
      including the Epithelial-Mesenchymal Transition (EMT). The secreted protein
      Transforming Growth Factor beta (TGFbeta) is a potent inducer of EMT in
      development and homeostasis. Importantly, the ability of TGFbeta to induce EMT
      has been implicated in promoting cancer invasion and metastasis, resistance to
      chemo/radio therapy, and maintenance of cancer stem cells. Interestingly, TGFbeta
      induced EMT and the SUMO system intersect with important implications for cancer
      formation and progression, and novel therapeutics identification.

PMID- 30096839
TI  - Dendrimers Show Promise for siRNA and microRNA Therapeutics.
AB  - The lack of an appropriate intracellular delivery system for therapeutic nucleic
      acids (TNAs) is a major problem in molecular biology, biotechnology, and
      medicine. A relatively new class of highly symmetrical hyperbranched polymers,
      called dendrimers, shows promise for transporting small TNAs into both cells and
      target tissues. Dendrimers have intrinsic advantages for this purpose: their
      physico-chemical and biological properties can be controlled during synthesis,
      and they are able to transport large numbers of TNA molecules that can
      specifically suppress the expression of single or multiple targeted genes.
      Numerous chemical modifications of dendrimers extend the biocompatibility of
      synthetic materials and allow targeted vectors to be designed for particular
      therapeutic purposes. This review summarizes the latest experimental data and
      trends in the medical application of various types of dendrimers and dendrimer
      based nanoconstructions as delivery systems for short small interfering RNAs
      (siRNAs) and microRNAs at the cell and organism levels. It provides an overview
      of the structural features of dendrimers, indicating their advantages over other
      types of TNA transporters.

PMID- 30096840
TI  - Clinically Relevant Anti-Inflammatory Agents for Chemoprevention of Colorectal
      Cancer: New Perspectives.
AB  - Substantial efforts are underway for prevention of early stages or recurrence of
      colorectal cancers (CRC) or new polyp formation by chemoprevention strategies.
      Several epidemiological, clinical and preclinical studies to date have supported
      the chemopreventive potentials of several targeted drug classes including non
      steroidal anti-inflammatory drugs (NSAIDs) (aspirin, naproxen, sulindac,
      celecoxib, and licofelone), statins and other natural agents-both individually,
      and in combinations. Most preclinical trials although were efficacious, only few
      agents entered clinical trials and have been proven to be potential
      chemopreventive agents for colon cancer. However, there are limitations for these
      agents that hinder their approval by the food and drug administration for
      chemoprevention use in high-risk individuals and in patients with early stages of
      CRC. In this review, we update the recent advancement in pre-clinical and
      clinical development of selected anti-inflammatory agents (aspirin, naproxen,
      sulindac, celecoxib, and licofelone) and their combinations for further
      development as novel colon cancer chemopreventive drugs. We provide further new
      perspectives from this old research, and insights into precision medicine
      strategies to overcome unwanted side-effects and overcoming strategies for colon
      cancer chemoprevention.

PMID- 30096841
TI  - Trans-Ethnic Mapping of BANK1 Identifies Two Independent SLE-Risk Linkage Groups
      Enriched for Co-Transcriptional Splicing Marks.
AB  - BANK1 is a susceptibility gene for several systemic autoimmune diseases in
      several populations. Using the genome-wide association study (GWAS) data from
      Europeans (EUR) and African Americans (AA), we performed an extensive fine
      mapping of ankyrin repeats 1 (BANK1). To increase the SNP density, we used
      imputation followed by univariate and conditional analysis, combined with a
      haplotypic and expression quantitative trait locus (eQTL) analysis. The data from
      Europeans showed that the associated region was restricted to a minimal and
      dependent set of SNPs covering introns two and three, and exon two. In AA, the
      signal found in the Europeans was split into two independent effects. All of the
      major risk associated SNPs were eQTLs, and the risks were associated with an
      increased BANK1 gene expression. Functional annotation analysis revealed the
      enrichment of repressive B cell epigenomic marks (EZH2 and H3K27me3) and a strong
      enrichment of splice junctions. Furthermore, one eQTL located in intron two,
      rs13106926, was found within the binding site for RUNX3, a transcriptional
      activator. These results connect the local genome topography, chromatin
      structure, and the regulatory landscape of BANK1 with co-transcriptional splicing
      of exon two. Our data defines a minimal set of risk associated eQTLs predicted to
      be involved in the expression of BANK1 modulated through epigenetic regulation
      and splicing. These findings allow us to suggest that the increased expression of
      BANK1 will have an impact on B-cell mediated disease pathways.

PMID- 30096843
TI  - Influence of the Non-Schmid Effects on the Ductility Limit of Polycrystalline
      Sheet Metals.
AB  - The yield criterion in rate-independent single crystal plasticity is most often
      defined by the classical Schmid law. However, various experimental studies have
      shown that the plastic flow of several single crystals (especially with Body
      Centered Cubic crystallographic structure) often exhibits some non-Schmid
      effects. The main objective of the current contribution is to study the impact of
      these non-Schmid effects on the ductility limit of polycrystalline sheet metals.
      To this end, the Taylor multiscale scheme is used to determine the mechanical
      behavior of a volume element that is assumed to be representative of the sheet
      metal. The mechanical behavior of the single crystals is described by a finite
      strain rate-independent constitutive theory, where some non-Schmid effects are
      accounted for in the modeling of the plastic flow. The bifurcation theory is
      coupled with the Taylor multiscale scheme to predict the onset of localized
      necking in the polycrystalline aggregate. The impact of the considered non-Schmid
      effects on both the single crystal behavior and the polycrystal behavior is
      carefully analyzed. It is shown, in particular, that non-Schmid effects tend to
      precipitate the occurrence of localized necking in polycrystalline aggregates and
      they slightly influence the orientation of the localization band.

PMID- 30096842
TI  - Chitosan-Based Nanofibrous Membrane Unit with Gradient Compositional and
      Structural Features for Mimicking Calcified Layer in Osteochondral Matrix.
AB  - Chitosan (CH), silk fibroin (SF), and hydroxyapatite (HA) were used to prepare
      CH/SF/HA composites and the resulting composites were electrospun into
      nanofibrous membrane units with gradient compositional and structural features.
      The optimal membrane unit was used together with CH/HA and CH/SF composites to
      fabricate a type of three-layer scaffold that is intended for osteochondral
      repair. The bottom layer of the scaffold was built with CH/HA composites and it
      served as a subchondral layer, the integrated nanofibrous membrane unit
      functioned as the middle layer for mimicking the calcified layer and the top
      layer was constructed using CH/SF composites for acting as a chondral layer. The
      nanofibrous membrane unit was found to be permeable to some molecules with
      limited molecular weight and was able to prevent the seeded cells from migrating
      cross the unit, functioning approximately like the calcified layer in the
      osteochondral matrix. Layered scaffolds showed abilities to promote the growth of
      both chondrocytes and osteoblasts that were seeded in their chondral layer and
      bony layer, respectively, and they were also able to support the phenotype
      preservation of seeded chondrocytes and the mineralization of neotissue in the
      bony layer. Results suggest that this type of layered scaffolds can function as
      an analogue of the osteochondral matrix and it has potential in osteochondral
      repair.

PMID- 30096844
TI  - Effects of Proteolytic and Lipolytic Enzyme Supplementations on Lipolysis and
      Proteolysis Characteristics of White Cheeses.
AB  - Effects of proteolytic (Neutrase, Bacillus subtilis-originate, 0.20 (P1) and 0.40
      g 100 L-1 (P2)) and lipolytic (Piccantase A, Mucor miehei-originated, 0.05 (L1)
      and 0.10 g 100 L-1 (L2)) enzyme supplementations to cheese milk on lipolysis and
      proteolysis characteristics of 90-day ripened cheese samples were investigated in
      this study. While enzyme supplementation did not have significant effects on
      titratable acidity, fat and protease-peptone nitrogen ratios of cheese samples,
      dry matter, salt, protein, water soluble nitrogen, 12% trichloroacetic acid
      soluble nitrogen ratio (TCA-SN), 5% phosphotungstic acid soluble nitrogen (PTA
      SN), casein nitrogen ratios, penetrometer value, total free fatty acids (TFFA)
      and total free amino acids (TFAA) were significantly influenced by enzyme
      supplementations. Individual free amino acids (15 of them) were also determined.
      Free amino acid contents of enzyme-supplemented cheeses were higher than the
      control cheese and the values increased in all cheese samples with the progress
      of ripening (p < 0.05). The highest amino acids in all periods of ripening were
      identified as glutamic acid, lysine, proline and aspartic acid. The major (Ca, P,
      Na, K, Mg) and minor (Zn, Fe, Cu, Mn) mineral levels of cheeses decreased with
      the progress of ripening and the effects of enzyme supplementations on these
      attributes (except for magnesium and manganese) were found to be significant (p <
      0.01). As to conclude, enzyme supplementations increased proteolysis and
      lipolysis and accelerated ripening and thus reduced ripening durations.
      Especially the enzyme ratios in P1 and L1 cheeses were found to be suitable for
      reducing the ripening period in White cheese without any adverse effects.

PMID- 30096845
TI  - TNFSF14/LIGHT, a Non-Canonical NF-kappaB Stimulus, Induces the HIF Pathway.
AB  - Non-canonical NF-kappaB signalling plays important roles in the development and
      function of the immune system but it also is deregulated in a number of
      inflammatory diseases. Although, NF-kappaB and HIF crosstalk has been documented,
      this has only been described following canonical NF-kappaB stimulation, involving
      RelA/p50 and the HIF-1 dimer. Here, we report that the non-canonical inducer
      TNFSF14/LIGHT leads to HIF induction and activation in cancer cells. We
      demonstrate that only HIF-2alpha is induced at the transcriptional level
      following non-canonical NF-kappaB activation, via a mechanism that is dependent
      on the p52 subunit. Furthermore, we demonstrate that p52 can bind to the HIF
      2alpha promoter in cells. These results indicate that non-canonical NF-kappaB can
      lead to HIF signalling implicating HIF-2alpha as one of the downstream effectors
      of this pathway in cells.

PMID- 30096846
TI  - Removal of the C6 Vaccinia Virus Interferon-beta Inhibitor in the Hepatitis C
      Vaccine Candidate MVA-HCV Elicited in Mice High Immunogenicity in Spite of
      Reduced Host Gene Expression.
AB  - Hepatitis C virus (HCV) represents a major global health problem for which a
      vaccine is not available. Modified vaccinia virus Ankara (MVA)-HCV is a unique
      HCV vaccine candidate based in the modified vaccinia virus Ankara (MVA) vector
      expressing the nearly full-length genome of HCV genotype 1a that elicits CD8+ T
      cell responses in mice. With the aim to improve the immune response of MVA-HCV
      and because of the importance of interferon (IFN) in HCV infection, we deleted in
      MVA-HCV the vaccinia virus (VACV) C6L gene, encoding an inhibitor of IFN-beta
      that prevents activation of the interferon regulatory factors 3 and 7 (IRF3 and
      IRF7). The resulting vaccine candidate (MVA-HCV DeltaC6L) expresses all HCV
      antigens and deletion of C6L had no effect on viral growth in permissive chicken
      cells. In human monocyte-derived dendritic cells, infection with MVA-HCV DeltaC6L
      triggered severe down-regulation of IFN-beta, IFN-beta-induced genes, and
      cytokines in a manner similar to MVA-HCV, as defined by real-time polymerase
      chain reaction (PCR) and microarray analysis. In infected mice, both vectors had
      a similar profile of recruited immune cells and induced comparable levels of
      adaptive and memory HCV-specific CD8+ T-cells, mainly against p7 + NS2 and NS3
      HCV proteins, with a T cell effector memory (TEM) phenotype. Furthermore,
      antibodies against E2 were also induced. Overall, our findings showed that while
      these vectors had a profound inhibitory effect on gene expression of the host,
      they strongly elicited CD8+ T cell and humoral responses against HCV antigens and
      to the virus vector. These observations add support to the consideration of these
      vectors as potential vaccine candidates against HCV.

PMID- 30096847
TI  - Lipid Composition but Not Curvature Is the Determinant Factor for the Low
      Molecular Mobility Observed on the Membrane of Virus-Like Vesicles.
AB  - Human Immunodeficiency Virus type-1 (HIV-1) acquires its lipid membrane from the
      plasma membrane of the infected cell from which it buds out. Previous studies
      have shown that the HIV-1 envelope is an environment of very low mobility, with
      the diffusion of incorporated proteins two orders of magnitude slower than in the
      plasma membrane. One of the reasons for this difference is thought to be the HIV
      1 membrane composition that is characterised by a high degree of rigidity and
      lipid packing, which has, until now, been difficult to assess experimentally. To
      further refine the model of the molecular mobility on the HIV-1 surface, we
      herein investigated the relative importance of membrane composition and curvature
      in simplified model membrane systems, large unilamellar vesicles (LUVs) of
      different lipid compositions and sizes (0.1-1 um), using super-resolution
      stimulated emission depletion (STED) microscopy-based fluorescence correlation
      spectroscopy (STED-FCS). Establishing an approach that is also applicable to
      measurements of molecule dynamics in virus-sized particles, we found, at least
      for the 0.1-1 um sized vesicles, that the lipid composition and thus membrane
      rigidity, but not the curvature, play an important role in the decreased
      molecular mobility on the vesicles' surface. This observation suggests that the
      composition of the envelope rather than the particle geometry contributes to the
      previously described low mobility of proteins on the HIV-1 surface. Our vesicle
      based study thus provides further insight into the dynamic properties of the
      surface of individual HIV-1 particles, as well as paves the methodological way
      towards better characterisation of the properties and function of viral lipid
      envelopes in general.

PMID- 30096849
TI  - High-Dimensional Probabilistic Fingerprinting in Wireless Sensor Networks Based
      on a Multivariate Gaussian Mixture Model.
AB  - The extensive deployment of wireless infrastructure provides a low-cost way to
      track mobile users in indoor environment. This paper demonstrates a prototype
      model of an accurate and reliable room location awareness system in a real public
      environment in which three typical problems arise. Firstly, a massive number of
      access points (APs) can be sensed leading to a high-dimensional classification
      problem. Secondly, heterogeneous devices record different received signal
      strength (RSS) levels because of the variations in chip-set and antenna
      attenuation. Thirdly, APs are not necessarily visible in every scanning cycle
      leading to missing data issue. This paper presents a probabilistic Wi-Fi
      fingerprinting method in a hidden Markov model (HMM) framework for mobile user
      tracking. To account for spatial correlation of the signal strengths from
      multiple APs, a Multivariate Gaussian Mixture Model (MVGMM) was fitted to model
      the probability distribution of RSS measurements in each cell. Furthermore, the
      unseen property of invisible AP was investigated in this research, and
      demonstrated the efficiency as a beneficial information to differentiate between
      cells. The proposed system is able to achieve comparable localisation
      performance. Filed test results achieve a reliable 97% localisation room level
      accuracy of multiple mobile users in a real university campus Wi-Fi network.

PMID- 30096848
TI  - Mitochondria-Targeted Antioxidants and Skeletal Muscle Function.
AB  - One of the main sources of reactive oxygen species (ROS) in skeletal muscle is
      the mitochondria. Prolonged or very high ROS exposure causes oxidative damage,
      which can be deleterious to muscle function, and as such, there is growing
      interest in targeting antioxidants to the mitochondria in an effort to prevent or
      treat muscle dysfunction and damage associated with disease and injury.
      Paradoxically, however, ROS also act as important signalling molecules in
      controlling cellular homeostasis, and therefore caution must be taken when
      supplementing with antioxidants. It is possible that mitochondria-targeted
      antioxidants may limit oxidative stress without suppressing ROS from non
      mitochondrial sources that might be important for cell signalling. Therefore, in
      this review, we summarise literature relating to the effect of mitochondria
      targeted antioxidants on skeletal muscle function. Overall, mitochondria-targeted
      antioxidants appear to exert beneficial effects on mitochondrial capacity and
      function, insulin sensitivity and age-related declines in muscle function.
      However, it seems that this is dependent on the type of mitochondrial-trageted
      antioxidant employed, and its specific mechanism of action, rather than simply
      targeting to the mitochondria.

PMID- 30096851
TI  - An Exploration of Psychosocial Pathways of Parks' Effects on Health: A
      Qualitative Study.
AB  - Urban green space has been positively associated with psychological and physical
      health. However, the linkage between exposure to parks and health outcomes
      remains unclear. The current study examined the meanings that people assign to
      city parks, as a way to understand the pathways by which parks exert their
      effects on health. We conducted qualitative interviews with twenty culturally
      diverse residents in New York City. Thematic analysis was performed on the
      qualitative data. Results showed that all themes identified were related to parks
      fulfilling a basic human need for connection to (1) family, loved ones, and
      friends; (2) community and neighborhood; (3) self; and (4) nature. Based on these
      data, we proposed a human-centered framework for future research and
      interventions aimed at catalyzing parks as a vehicle to improve health and
      wellbeing. A human-centered approach emphasizes targeting the deep-seated needs
      and values of those we seek to engage and for whom health promotion and disease
      prevention efforts are designed. Our study shows that park transformations need
      to incorporate careful considerations of the human need for connection on
      multiple levels, so that park usage and its consequent health benefits may be
      optimized.

PMID- 30096850
TI  - Golgi Reassembly and Stacking Protein (GRASP) Participates in Vesicle-Mediated
      RNA Export in Cryptococcus Neoformans.
AB  - Golgi reassembly and stacking protein (GRASP) is required for polysaccharide
      secretion and virulence in Cryptococcus neoformans. In fungal species,
      extracellular vesicles (EVs) participate in the export of polysaccharides,
      proteins and RNA. In the present work, we investigated if EV-mediated RNA export
      is functionally connected with GRASP in C. neoformans using a graspDelta mutant.
      Since GRASP-mediated unconventional secretion involves autophagosome formation in
      yeast, we included the atg7Delta mutant with defective autophagic mechanisms in
      our analysis. All fungal strains exported EVs but deletion of GRASP or ATG7
      profoundly affected vesicular dimensions. The mRNA content of the graspDelta EVs
      differed substantially from that of the other two strains. The transcripts
      associated to the endoplasmic reticulum were highly abundant transcripts in
      graspDelta EVs. Among non-coding RNAs (ncRNAs), tRNA fragments were the most
      abundant in both mutant EVs but graspDelta EVs alone concentrated 22 exclusive
      sequences. In general, our results showed that the EV RNA content from atg7Delta
      and WT were more related than the RNA content of graspDelta, suggesting that
      GRASP, but not the autophagy regulator Atg7, is involved in the EV export of RNA.
      This is a previously unknown function for a key regulator of unconventional
      secretion in eukaryotic cells.

PMID- 30096852
TI  - Pathogenesis of the Candida parapsilosis Complex in the Model Host Caenorhabditis
      elegans.
AB  - Caenorhabditiselegans is a valuable tool as an infection model toward the study
      of Candida species. In this work, we endeavored to develop a C. elegans
      Candidaparapsilosis infection model by using the fungi as a food source. Three
      species of the C. parapsilosis complex (C.parapsilosis (sensustricto),
      Candidaorthopsilosis and Candidametapsilosis) caused infection resulting in C.
      elegans killing. All three strains that comprised the complex significantly
      diminished the nematode lifespan, indicating the virulence of the pathogens
      against the host. The infection process included invasion of the intestine and
      vulva which resulted in organ protrusion and hyphae formation. Importantly,
      hyphae formation at the vulva opening was not previously reported in C. elegans
      Candida infections. Fungal infected worms in the liquid assay were susceptible to
      fluconazole and caspofungin and could be found to mount an immune response
      mediated through increased expression of cnc-4, cnc-7, and fipr-22/23. Overall,
      the C. elegans-C. parapsilosis infection model can be used to model C.
      parapsilosis host-pathogen interactions.

PMID- 30096854
TI  - Measurement and Isolation of Thermal Stress in Silicon-On-Glass MEMS Structures.
AB  - The mechanical stress in silicon-on-glass MEMS structures and a stress isolation
      scheme were studied by analysis and experimentation. Double-ended tuning forks
      (DETFs) were used to measure the stress based on the stress-frequency conversion
      effect. Considering the coefficients of thermal expansion (CTEs) of silicon and
      glass and the temperature coefficient of the Young's modulus of silicon, the
      sensitivity of the natural frequency to temperature change was analyzed. A stress
      isolation mechanism composed of annular isolators and a rigid frame is proposed
      to prevent the structure inside the frame from being subjected to thermal
      stresses. DETFs without and with one- or two-stage isolation frames with the
      orientations <110> and <100> were designed, the stress and natural frequency
      variations with temperature were simulated and measured. The experimental results
      show that in the temperature range of -50  degrees C to 85  degrees C, the stress
      varied from -18 MPa to 10 MPa in the orientation <110> and -11 MPa to 5 MPa in
      the orientation <100>. For the 1-stage isolated DETF of <110> orientation, the
      measured stress variation was only 0.082 MPa. The thermal stress can be mostly
      rejected by a stress isolation structure, which is applicable in the design of
      stress-sensitive MEMS sensors and actuators.

PMID- 30096853
TI  - Augmented Insulin and Leptin Resistance of High Fat Diet-Fed APPswe/PS1dE9
      Transgenic Mice Exacerbate Obesity and Glycemic Dysregulation.
AB  - Alzheimer's disease (AD), a progressive neurodegenerative disease is highly
      associated with metabolic syndromes. We previously demonstrated that glycemic
      dysregulation and obesity are augmented in high fat diet (HFD)-treated
      APPswe/PS1dE9 (APP/PS1) transgenic mice. In the current study, the underlying
      mechanism mediating exacerbated metabolic stresses in HFD APP/PS1 transgenic mice
      was further examined. APP/PS1 mice developed insulin resistance and,
      consequently, impaired glucose homeostasis after 10 weeks on HFD. [18F]-2-fluoro
      2-deoxy-d-glucose ([18F]-FDG) positron emission tomography showed that
      interscapular brown adipose tissue is vulnerable to HFD and AD-related pathology.
      Chronic HFD induced hyperphagia, with limited effects on basal metabolic rates in
      APP/PS1 transgenic mice. Excessive food intake may be caused by impairment of
      leptin signaling in the hypothalamus because leptin failed to suppress the food
      intake of HFD APP/PS1 transgenic mice. Leptin-induced pSTAT3 signaling in the
      arcuate nucleus was attenuated. Dysregulated energy homeostasis including
      hyperphagia and exacerbated obesity was elicited prior to the presence of the
      amyloid pathology in the hypothalamus of HFD APP/PS1 transgenic mice;
      nevertheless, cortical neuroinflammation and the level of serum Abeta and IL-6
      were significantly elevated. Our study demonstrates the pivotal role of AD
      related pathology in augmenting HFD-induced insulin and leptin resistance and
      impairing hypothalamic regulation of energy homeostasis.

PMID- 30096855
TI  - Surface Alloying in Silver-Cobalt through a Second Wave Solution Combustion
      Synthesis Technique.
AB  - Herein, we report the synthesis of silver-cobalt nanopowders using three
      different modes of solution combustion synthesis, and we present the effects of
      the synthesis conditions on particle morphology. The synthesized nanoparticles
      were characterized using X-ray diffraction (XRD), Scanning electron microscopy
      (SEM), Fourier transform infrared spectroscopy (FTIR), UV-Visible
      spectrophotometer (UV-vis), Transmission electron microscopy (TEM), and X-Ray
      Photoelectron Spectroscopy (XPS) to understand the structural and elemental
      properties. When Co is synthesized over Ag in a second wave of combustion, peak
      shifts observed in XRD and XPS show a change in the cell parameters and prove the
      existence of a strong electronic interaction between Ag and Co. Better control of
      mixing and alloying through the second wave combustion synthesis mode (SWCS) was
      evident. The sequence of combustion affects the structure and composition of the
      material. SWCS reduces the amount of carbon content, as compared to single-stage
      combustion, and the combustion of carbon is followed by a rearrangement of atoms.

PMID- 30096856
TI  - Novel Insights into Concepts and Directionality of Maternal-Fetal Cholesterol
      Transfer across the Human Placenta.
AB  - Cholesterol is indispensable for cellular membrane composition and function. It
      is also a precursor for the synthesis of steroid hormones, which promote, among
      others, the maturation of fetal organs. A role of the ATP-binding-cassette
      transporter-A1 (ABCA1) in the transport of maternal cholesterol to the fetus was
      suggested by transferring cholesterol to apolipoprotein-A-1 (apo-A1), but the
      directionality of the apoA-1/ABCA1-dependent cholesterol transport remains
      unclear. We isolated primary trophoblasts from term placentae to test the
      hypotheses that (1) apoA-1/ABCA1 dispatches cholesterol mainly towards the fetus
      to support fetal developmental maturation at term, and (2) differentiated
      syncytiotrophoblasts (STB) exert higher cholesterol transport activity than
      undifferentiated cytotrophoblasts (CTB). As experimental models, we used (1)
      trophoblast monolayers grown on Transwell(r) system consisting of apical
      (maternal-like) and basal (fetal-like) compartments, and (2) trophoblasts grown
      on conventional culture plates at CTB and STB stages. Surprisingly, apoA-1
      mediated cholesterol efflux operated almost exclusively at the apical-maternal
      side, where ABCA1 was also localized by immunofluorescence. We found greater
      cholesterol efflux capacity in STB, which was increased by liver-X-receptor
      agonist treatment and decreased by ABCA1 inhibition. We conclude that at term the
      apoA-1/ABCA1 pathway is rather involved in cholesterol transport to the mother
      than in transfer to the fully developed fetus.

PMID- 30096857
TI  - Hexagonal Boron Nitride Functionalized with Au Nanoparticles-Properties and
      Potential Biological Applications.
AB  - Hexagonal boron nitride is often referred to as white graphene. This is a 2D
      layered material, with a structure similar to graphene. It has gained many
      applications in cosmetics, dental cements, ceramics etc. Hexagonal boron nitride
      is also used in medicine, as a drug carrier similar as graphene or graphene
      oxide. Here we report that this material can be exfoliated in two steps: chemical
      treatment (via modified Hummers method) followed by the sonication treatment.
      Afterwards, the surface of the obtained material can be efficiently
      functionalized with gold nanoparticles. The mitochondrial activity was not
      affected in L929 and MCF-7 cell line cultures during 24-h incubation, whereas
      longer incubation (for 48, and 72 h) with this nanocomposite affected the
      cellular metabolism. Lysosome functionality, analyzed using the NR uptake assay,
      was also reduced in both cell lines. Interestingly, the rate of MCF-7 cell
      proliferation was reduced when exposed to h-BN loaded with gold nanoparticles. It
      is believed that h-BN nanocomposite with gold nanoparticles is an attractive
      material for cancer drug delivery and photodynamic therapy in cancer killing.

PMID- 30096858
TI  - Design of Binary-Sequence Zone Plates in High Wavelength Domains.
AB  - The design of zone plates is an important topic in many areas of physics, such as
      optics, X-rays, microwaves or ultrasonics. In this paper, a zone plate design
      method, which provides high flexibility in the shaping of the focusing profile,
      is analyzed. This flexibility is achieved through the use of binary sequences
      that produce zone plates with different properties and applications. It is shown
      that this binary-sequence method works properly at low wavelengths, but requires
      a modification term to work accurately in high wavelength domains. This
      additional term extends this powerful design method to any wavelength. Simulation
      results show acoustic focusing profiles for Fresnel, Fibonacci and Cantor zone
      plates operating at a wavelength of 1.5 mm without any distortion.

PMID- 30096859
TI  - Large-Scale Functional Analysis of CRP-Mediated Feed-Forward Loops.
AB  - Feed-forward loops (FFLs) represent an important and basic network motif to
      understand specific biological functions. Cyclic-AMP (cAMP) receptor protein
      (CRP), a transcription factor (TF), mediates catabolite repression and regulates
      more than 400 genes in response to changes in intracellular concentrations of
      cAMP in Escherichia coli. CRP participates in some FFLs, such as araBAD and
      araFGH operons and adapts to fluctuating environmental nutrients, thereby
      enhancing the survivability of E. coli. Although computational simulations have
      been conducted to explore the potential functionality of FFLs, a comprehensive
      study on the functions of all structural types on the basis of in vivo data is
      lacking. Moreover, the regulatory role of CRP-mediated FFLs (CRP-FFLs) remains
      obscure. We identified 393 CRP-FFLs in E. coli using EcoCyc and RegulonDB. Dose
      response genomic microarray of E. coli revealed dynamic gene expression of each
      target gene of CRP-FFLs in response to a range of cAMP dosages. All eight types
      of FFLs were present in CRP regulon with various expression patterns of each CRP
      FFL, which were further divided into five functional groups. The microarray and
      reported regulatory relationships identified 202 CRP-FFLs that were directly
      regulated by CRP in these eight types of FFLs. Interestingly, 34% (147/432) of
      genes were directly regulated by CRP and CRP-regulated TFs, which indicates that
      these CRP-regulated genes were also regulated by other CRP-regulated TFs
      responding to environmental signals through CRP-FFLs. Furthermore, we applied
      gene ontology annotation to reveal the biological functions of CRP-FFLs.

PMID- 30096861
TI  - A "Turn-On" Fluorescence Copper Biosensor Based on DNA Cleavage-Dependent
      Graphene Oxide-dsDNA-CdTe Quantum Dots Complex.
AB  - A novel "turn-on" fluorescent copper biosensor is developed successfully based on
      the graphene oxide (GO)-dsDNA-CdTe quantum dots (QDs) complex via chemical
      crosslink method. The optical and structure properties of GO-dsDNA-CdTe QDs
      complex are studied by fluorescence (FL) spectra and transmission electron
      microscopy (TEM) in detail. It is demonstrated that the fluorescence quenching of
      CdTe QDs is a process of fluorescence resonance energy transfer (FRET) due to the
      essential surface and quenching properties of two-dimensional GO. Copper ions
      induce the catalytic reaction of DNA chain and irreversibly break at the cleavage
      site, which will cause the G-quadruplex formation, moreover further result in the
      CdTe QDs separated from GO and restored its fluorescence. Therefore, a
      significant recovery effect on the fluorescence of the GO-dsDNA-CdTe QDs complex
      is observed in the presence of copper ions. The fluorescence responses are
      concentration-dependent and can be well described by a linear equation. Compared
      with other metal ions, the sensor performs good selectivity for copper ions.

PMID- 30096860
TI  - Impact of Fungal MAPK Pathway Targets on the Cell Wall.
AB  - The fungal cell wall is an extracellular organelle that provides structure and
      protection to cells. The cell wall also influences the interactions of cells with
      each other and surfaces. The cell wall can be reorganized in response to changing
      environmental conditions and different types of stress. Signaling pathways
      control the remodeling of the cell wall through target proteins that are in many
      cases not well defined. The Mitogen Activated Protein Kinase pathway that
      controls filamentous growth in yeast (fMAPK) was required for normal growth in
      media containing the cell wall perturbing agent Calcofluor White (CFW). A mass
      spectrometry (MASS-SPEC) approach and analysis of expression profiling data
      identified cell wall proteins and modifying enzymes whose levels were influenced
      by the fMAPK pathway. These include Flo11p, Flo10p, Tip1p, Pry2p and the
      mannosyltransferase, Och1p. Cells lacking Flo11p or Och1p were sensitive to CFW.
      The identification of cell wall proteins controlled by a MAPK pathway may provide
      insights into how signaling pathways regulate the cell wall.

PMID- 30096864
TI  - 4E Music Pedagogy and the Principles of Self-Organization.
AB  - Recent approaches in the cognitive and psychological sciences conceive of mind as
      an Embodied, Embedded, Extended, and Enactive (or 4E) phenomenon. While this has
      stimulated important discussions and debates across a vast array of disciplines,
      its principles, applications, and explanatory power have not yet been properly
      addressed in the domain of musical development. Accordingly, it remains unclear
      how the cognitive processes involved in the acquisition of musical skills might
      be understood through the lenses of this approach, and what this might offer for
      practical areas like music education. To begin filling this gap, the present
      contribution aims to explore central aspects of music pedagogy through the lenses
      of 4E cognitive science. By discussing cross-disciplinary research in music,
      pedagogy, psychology, and philosophy of mind, we will provide novel insights that
      may help inspire a richer understanding of what musical learning entails. In
      doing so, we will develop conceptual bridges between the notion of 'autopoiesis'
      (the property of continuous self-regeneration that characterizes living systems)
      and the emergent dynamics contributing to the flourishing of one's musical life.
      This will reveal important continuities between a number of new teaching
      approaches and principles of self-organization. In conclusion, we will briefly
      consider how these conceptual tools align with recent work in interactive
      cognition and collective music pedagogy, promoting the close collaboration of
      musicians, pedagogues, and cognitive scientists.

PMID- 30096862
TI  - Understanding the Biology of Self-Renewing Macrophages.
AB  - Macrophages reside in specific territories in organs, where they contribute to
      the development, homeostasis, and repair of tissues. Recent work has shown that
      the size of tissue macrophage populations has an impact on tissue functions and
      is determined by the balance between replenishment and elimination. Macrophage
      replenishment is mainly due to self-renewal of macrophages, with a secondary
      contribution from blood monocytes. Self-renewal is a recently discovered trait of
      macrophages, which can have a major impact on their physiological functions and
      hence on the wellbeing of the organism. In this review, I discuss our current
      understanding of the developmental origin of self-renewing macrophages and the
      mechanisms used to maintain a physiologically stable macrophage pool.

PMID- 30096865
TI  - Eco-Friendly Cavity-Containing Iron Oxides Prepared by Mild Routes as Very
      Efficient Catalysts for the Total Oxidation of VOCs.
AB  - Iron oxides (FeOx) are non-toxic, non-expensive and environmentally friendly
      compounds, which makes them good candidates for many industrial applications,
      among them catalysis. In the present article five catalysts based on FeOx were
      synthesized by mild routes: hydrothermal in subcritical and supercritical
      conditions (Fe-HT, Few200, Few450) and solvothermal (Fe-ST1 and Fe-ST2). The
      catalytic activity of these catalysts was studied for the total oxidation of
      toluene using very demanding conditions with high space velocities and including
      water and CO2 in the feed. The samples were characterized by X-ray diffraction
      (XRD), scanning and high-resolution transmission electron microscopy (SEM and
      HRTEM), X-ray photoelectron spectroscopy (XPS) and nitrogen adsorption-desorption
      isotherms. It was observed that the most active catalyst was a cavity-containing
      porous sample prepared by a solvothermal method with a relatively high surface
      area (55 m2 g-1) and constituted by flower-like aggregates with open cavities at
      the catalyst surface. This catalyst displayed superior performance (100% of
      toluene conversion at 325  degrees C using highly demanding conditions) and this
      performance can be maintained for several catalytic cycles. Interestingly, the
      porous iron oxides present not only a higher catalytic activity than the non
      porous but also a higher specific activity per surface area. The high activity of
      this catalyst has been related to the possible synergistic effect of
      compositional, structural and microstructural features emphasizing the role of
      the surface area, the crystalline phase present, and the properties of the
      surface.

PMID- 30096867
TI  - Related Factors of Suicidal Ideation among North Korean Refugee Youth in South
      Korea.
AB  - This study investigated the factors associated with suicidal ideation among 174
      North Korean refugees (aged 13-27 years) residing in South Korea. Specifically,
      we compared sociodemographic, familial, social, and psychological characteristics
      between participants with and without suicidal ideation. Twenty-nine refugees
      (16.7%) had exhibited suicidal ideation in the past 12 months. These refugees had
      significantly lower levels of familial cohesion (U = 1459.0; p < 0.001), self
      esteem (U = 1032.0; p < 0.001), and resilience (U = 1190.0; p < 0.001), as well
      as higher levels of expressional suppression (U = 1202.5; p < 0.001) and post
      traumatic stress disorder symptoms (U = 1303.0; p = 0.001), (with Cohen's d >
      0.5), compared to those without suicidal ideation. A multiple logistic regression
      analysis showed that the level of emotional suppression and familial cohesion
      were significantly associated with suicidal ideation, after controlling for the
      other variables. Familial and individual interventions, particularly those
      focused on encouraging emotional expression and familial cohesion, will be useful
      for North Korean refugee youth, who have a high risk of suicide.

PMID- 30096866
TI  - Cembranoid-Related Metabolites and Biological Activities from the Soft Coral
      Sinularia flexibilis.
AB  - Five new cembranoid-related diterpenoids, namely, flexibilisins D and E (1 and
      2), secoflexibilisolides A and B (3 and 4), and flexibilisolide H (5), along with
      nine known compounds (6-14), were isolated from the soft coral Sinularia
      flexibilis. Their structures were established by extensive spectral analysis.
      Compound 3 possesses an unusual skeleton that could be biogenetically derived
      from cembranoids. The cytotoxicity and anti-inflammatory activities of the
      isolates were investigated, and the results showed that dehydrosinulariolide (7)
      and 11-epi-sinulariolide acetate (8) exhibited cytotoxicity toward a limited
      panel of cancer cell lines and 14-deoxycrassin (9) displayed anti-inflammatory
      activity by inhibition of superoxide anion generation and elastase release in N
      formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLF/CB)-induced human
      neutrophils.

PMID- 30096868
TI  - Evaluation of a Computer-Aided Diagnosis System in the Classification of Lesions
      in Breast Strain Elastography Imaging.
AB  - Purpose: Evaluation of the performance of a computer-aided diagnosis (CAD) system
      based on the quantified color distribution in strain elastography imaging to
      evaluate the malignancy of breast tumors. Methods: The database consisted of 31
      malignant and 52 benign lesions. A radiologist who was blinded to the diagnosis
      performed the visual analysis of the lesions. After six months with no eye
      contact on the breast images, the same radiologist and other two radiologists
      manually drew the contour of the lesions in B-mode ultrasound, which was masked
      in the elastography image. In order to measure the amount of hard tissue in a
      lesion, we developed a CAD system able to identify the amount of hard tissue,
      represented by red color, and quantify its predominance in a lesion, allowing
      classification as soft, intermediate, or hard. The data obtained with the CAD
      system were compared with the visual analysis. We calculated the sensitivity,
      specificity, and area under the curve (AUC) for the classification using the CAD
      system from the manual delineation of the contour by each radiologist. Results:
      The performance of the CAD system for the most experienced radiologist achieved
      sensitivity of 70.97%, specificity of 88.46%, and AUC of 0.853. The system
      presented better performance compared with his visual diagnosis, whose
      sensitivity, specificity, and AUC were 61.29%, 88.46%, and 0.829, respectively.
      The system obtained sensitivity, specificity, and AUC of 67.70%, 84.60%, and
      0.783, respectively, for images segmented by Radiologist 2, and 51.60%, 92.30%,
      and 0.771, respectively, for those segmented by the Resident. The intra-class
      correlation coefficient was 0.748. The inter-observer agreement of the CAD system
      with the different contours was good in all comparisons. Conclusions: The
      proposed CAD system can improve the radiologist performance for classifying
      breast masses, with excellent inter-observer agreement. It could be a promising
      tool for clinical use.

PMID- 30096869
TI  - Recipes for Determining Doneness in Poultry Do Not Provide Appropriate
      Information Based on US Government Guidelines.
AB  - Research has shown that consumers use unsafe food handling practices when
      preparing poultry, which can increase the risk of foodborne illness such as
      salmonellosis or campylobacteriosis. Recipes from cookbooks, magazines, and the
      internet commonly are used as sources for consumers to prepare food in homes and
      the expectation is that food will be safe when prepared. According to the United
      States Department of Agriculture (USDA), using a thermometer properly is the only
      way to accurately check for doneness of poultry. The objective of this study was
      to assess poultry recipes, including recipes for whole birds and poultry parts,
      to determine if food safety information concerning thermometer use was included
      within the recipe. Poultry recipes (n = 474) were collected from 217 cookbooks,
      28 magazines, 59 websites, and seven blogs. Approximately 33.5% of the recipes
      contained a specific temperature for doneness, with 73% of those cooked to >=165 
      degrees F/74  degrees C, as recommended by USDA. Ninety-four percent of recipes
      used cooking time and about half of the recipes used visual measurements, such as
      color or juices running clear, to determine doneness. This study showed that most
      recipes do not contain appropriate information to assure safe cooking of poultry
      by consumers. Modifying recipes by adding food safety information, such as
      thermometer use and proper temperatures, could increase the use of proper food
      preparation behaviors by consumers.

PMID- 30096863
TI  - Individualized Immunological Data for Precise Classification of OCD Patients.
AB  - Obsessive-compulsive disorder (OCD) affects about 2% of the general population,
      for which several etiological factors were identified. Important among these is
      immunological dysfunction. This review aims to show how immunology can inform
      specific etiological factors, and how distinguishing between these etiologies is
      important from a personalized treatment perspective. We found discrepancies
      concerning cytokines, raising the hypothesis of specific immunological
      etiological factors. Antibody studies support the existence of a potential
      autoimmune etiological factor. Infections may also provoke OCD symptoms, and
      therefore, could be considered as specific etiological factors with specific
      immunological impairments. Finally, we underline the importance of distinguishing
      between different etiological factors since some specific treatments already
      exist in the context of immunological factors for the improvement of classic
      treatments.

PMID- 30096870
TI  - Myocardial Contraction during the Diastolic Isovolumetric Period: Analysis of
      Longitudinal Strain by Means of Speckle Tracking Echocardiography.
AB  - BACKGROUND: According to the ventricular myocardial band model, the diastolic
      isovolumetric period is a contraction phenomenon. Our objective was to employ
      speckle-tracking echocardiography (STE) to analyze myocardial deformation of the
      left ventricle (LV) and to confirm if it supports the myocardial band model.
      METHODS: This was a prospective observational study in which 90 healthy
      volunteers were recruited. We evaluated different types of postsystolic
      shortening (PSS) from an LV longitudinal strain study. Duration of latest
      deformation (LD) was calculated as the time from the start of the QRS complex of
      the ECG to the latest longitudinal deformation peak in the 18 segments of the LV.
      RESULTS: The mean age of our subjects was 50.3 +/- 11.1 years. PSS was observed
      in 48.4% of the 1620 LV segments studied (19.8%, 13.5%, and 15.1% in the basal,
      medial, and apical regions, respectively). PSS was more frequent in the basal,
      medial septal, and apical anteroseptal segments (>50%). LD peaked in the
      interventricular septum and in the basal segments of the LV. CONCLUSIONS: The
      pattern of PSS and LD revealed by STE suggests there is contraction in the
      postsystolic phase of the cardiac cycle. The anatomical location of the segments
      in which this contraction is most frequently observed corresponds to the main
      path of the ascending component of the myocardial band. This contraction can be
      attributed to the protodiastolic untwisting of the LV.

PMID- 30096871
TI  - Olive Mild Mosaic Virus Coat Protein and P6 Are Suppressors of RNA Silencing, and
      Their Silencing Confers Resistance against OMMV.
AB  - RNA silencing is an important defense mechanism in plants, yet several plant
      viruses encode proteins that suppress this mechanism. In this study, the genome
      of the Olive mild mosaic virus (OMMV) was screened for silencing suppressors. The
      full OMMV cDNA and 5 OMMV open reading frames (ORFs) were cloned into the Gateway
      binary vector pK7WG2, transformed into Agrobacterium tumefaciens, and
      agroinfiltrated into N. benthamiana 16C plants. CP and p6 showed suppressor
      activity, with CP showing significantly higher activity than p6, yet activity
      that was lower than the full OMMV, suggesting a complementary action of CP and
      p6. These viral suppressors were then used to induce OMMV resistance in plants
      based on RNA silencing. Two hairpin constructs targeting each suppressor were
      agroinfiltrated in N. benthamiana plants, which were then inoculated with OMMV
      RNA. When silencing of both suppressors was achieved, a significant reduction in
      viral accumulation and symptom attenuation was observed as compared to those of
      the controls, as well as to when each construct was used alone, proving them to
      be effective against OMMV infection. This is the first time that a silencing
      suppressor was found in a necrovirus, and that two independent proteins act as
      silencing suppressors in a virus member of the Tombusviridae family.

PMID- 30096872
TI  - Use of MALDI-TOF MS to Discriminate between Biofilm-Producer and Non-Producer
      Strains of Staphylococcus epidermidis.
AB  - For the management of Staphylococci coagulase-negative infection, often related
      to biofilm formation, rapid and accurate identification is necessary in choosing
      a correct antibiotic therapy. Matrix-assisted laser desorption ionization time-of
      flight (MALDI-TOF) mass spectrometry (MS) is becoming increasingly important for
      bacterial identification over traditional methods. Our aim was to validate the
      use of MALDI to discriminate Staphylococcus epidermidis biofilm-producing
      strains. Clinical strains coming from suture wires were identified and their
      protein profiles were compared to that obtained from two ATCC reference strains
      (biofilm producer and non-producer). MALDI identified the eighteen isolates as S.
      epidermidis, combining sixteen profiles with the biofilm producer and two with
      the non-producer, confirming the results of crystal violet assay. Our data
      highlight that MALDI can be considered a good tool to discriminate between
      biofilm-producer and non-producer strains of S. epidermidis, thus helping to
      establish an effective antibiotic therapy.

PMID- 30096873
TI  - Na/K-ATPase Signaling and Cardiac Pre/Postconditioning with Cardiotonic Steroids.
AB  - The first reports of cardiac Na/K-ATPase signaling, published 20 years ago, have
      opened several major fields of investigations into the cardioprotective action of
      low/subinotropic concentrations of cardiotonic steroids (CTS). This review
      focuses on the protective cardiac Na/K-ATPase-mediated signaling triggered by low
      concentrations of ouabain and other CTS, in the context of the enduring debate
      over the use of CTS in the ischemic heart. Indeed, as basic and clinical research
      continues to support effectiveness and feasibility of conditioning interventions
      against ischemia/reperfusion injury in acute myocardial infarction (AMI), the
      mechanistic information available to date suggests that unique features of CTS
      based conditioning could be highly suitable, alone /or as a combinatory approach.

PMID- 30096874
TI  - Bias Adjustment Techniques Are Underutilized in HIV Sexual Risk Estimation: A
      Systematic Review.
AB  - Background: Valid measurement of determinants of HIV infection among men who have
      sex with men (MSM) is critical for intervention planning and resource allocation.
      However, sexual minority research concerning HIV risk often relies on proxy
      exposures of sexual behaviors such as sexual orientation and partner gender.
      Inferring high risk sexual behaviors (i.e., condomless anal intercourse) from
      these proxies inaccurately captures HIV risk, but few studies have attempted to
      correct for this bias. Methods: We performed a systematic review of
      methodological practices for estimating risk of HIV infection among MSM. Results:
      We identified 32 studies in which high risk sexual behavior was assessed: 82% (n
      = 26) measured and used sexual risk behaviors (e.g., condomless anal intercourse
      or sexual positioning) to assess risk of HIV infection; 9% (n = 3) used proxy
      measures; and 9% (n = 3) used both behavior and proxy variables. Various
      treatments of misclassification reported by investigators included the following:
      82% (n = 26) discussed misclassification of sexual behavior as a potential
      limitation; however, among these studies, no attempts were made to correct
      misclassification; 12% (n = 4) did not report exposure misclassification, and 6%
      (n = 2) explicitly considered this information bias and conducted a Bayesian
      approach to correct for misclassification. Conclusions: Our systematic review
      indicates that a majority of studies engaging in collecting primary data have
      taken additional steps to acquire detailed information regarding sexual risk
      behaviors. However, reliance on population-based surveys may still lead to
      potentially biased estimates. Thus, bias analytic techniques are potential tools
      to control for any suspected biases.

PMID- 30096877
TI  - Correction: Chang, C.-H.; et al. Secreted Protein Acidic and Rich in Cysteine
      (SPARC) Enhances Cell Proliferation, Migration, and Epithelial Mesenchymal
      Transition, and SPARC Expression Is Associated with Tumor Grade in Head and Neck
      Cancer. Int. J. Mol. Sci. 2017, 18, 1556.
AB  - We would like to submit the correction to our published paper [1]. [...].

PMID- 30096876
TI  - Coffee Consumption and Whole-Blood Gene Expression in the Norwegian Women and
      Cancer Post-Genome Cohort.
AB  - Norwegians are the second highest consumers of coffee in the world. Lately,
      several studies have suggested that beneficial health effects are associated with
      coffee consumption. By analyzing whole-blood derived, microarray based mRNA gene
      expression data from 958 cancer-free women from the Norwegian Women and Cancer
      Post-Genome Cohort, we assessed the potential associations between coffee
      consumption and gene expression profiles and elucidated functional
      interpretation. Of the 958 women included, 132 were considered low coffee
      consumers (<1 cup of coffee/day), 422 moderate coffee consumers (1-3 cups of
      coffee/day), and 404 were high coffee consumers (>3 cups of coffee/day). At a
      false discovery rate <0.05, 139 genes were differentially expressed between high
      and low consumers of coffee. A subgroup of 298 nonsmoking, low tea consumers was
      established to isolate the effects of coffee from smoking and potential caffeine
      containing tea consumption. In this subgroup, 297 genes were found to be
      differentially expressed between high and low coffee consumers. Results indicate
      differentially expressed genes between high and low consumers of coffee with
      functional interpretations pointing towards a possible influence on metabolic
      pathways and inflammation.

PMID- 30096875
TI  - The Therapeutic Strategy of HDAC6 Inhibitors in Lymphoproliferative Disease.
AB  - Histone deacetylases (HDACs) are master regulators of chromatin remodeling,
      acting as epigenetic regulators of gene expression. In the last decade,
      inhibition of HDACs has become a target for specific epigenetic modifications
      related to cancer development. Overexpression of HDAC has been observed in
      several hematologic malignancies. Therefore, the observation that HDACs might
      play a role in various hematologic malignancies has brought to the development of
      HDAC inhibitors as potential antitumor agents. Recently, the class IIb, HDAC6,
      has emerged as one potential selective HDACi. This isoenzyme represents an
      important pharmacological target for selective inhibition. Its selectivity may
      reduce the toxicity related to the off-target effects of pan-HDAC inhibitors.
      HDAC6 has also been studied in cancer especially for its ability to coordinate a
      variety of cellular processes that are important for cancer pathogenesis. HDAC6
      has been reported to be overexpressed in lymphoid cells and its inhibition has
      demonstrated activity in preclinical and clinical study of lymphoproliferative
      disease. Various studies of HDAC6 inhibitors alone and in combination with other
      agents provide strong scientific rationale for the evaluation of these new agents
      in the clinical setting of hematological malignancies. In this review, we
      describe the HDACs, their inhibitors, and the recent advances of HDAC6
      inhibitors, their mechanisms of action and role in lymphoproliferative disorders.

PMID- 30096878
TI  - Blackberry Feeding Increases Fat Oxidation and Improves Insulin Sensitivity in
      Overweight and Obese Males.
AB  - Berries and other anthocyanin-rich treatments have prevented weight gain and
      adiposity in rodent models of diet-induced obesity. Their efficacy may be
      explained by modulation of energy substrate utilization. However, this effect has
      never been translated to humans. The objective of this study was to evaluate the
      effects of berry intake on energy substrate use and glucoregulation in volunteers
      consuming a high-fat diet. Twenty-seven overweight or obese men were enrolled in
      a randomized, placebo-controlled crossover study with two treatment periods.
      Subjects were fed an investigator controlled, high-fat (40% of energy from fat)
      diet which contained either 600 g/day blackberries (BB, 1500 mg/day flavonoids)
      or a calorie and carbohydrate matched amount of gelatin (GEL, flavonoid-free
      control) for seven days prior to a meal-based glucose tolerance test (MTT) in
      combination with a 24 h stay in a room-sized indirect calorimeter. The washout
      period that separated the treatment periods was also seven days. The BB treatment
      resulted in a significant reduction in average 24 h respiratory quotient (RQ)
      (0.810 vs. 0.817, BB vs. GEL, p = 0.040), indicating increased fat oxidation. RQ
      during the MTT was significantly lower with the BB treatment (0.84) compared to
      GEL control (0.85), p = 0.004. A 4 h time isolation during dinner showed similar
      treatment effects, where RQ was reduced and fat oxidation increased with BB
      (0.818 vs. 0.836, 28 vs. 25 g, respectively; BB vs. GEL treatments). The glucose
      AUC was not different between the BB and GEL treatments during the MTT (3488 vs.
      4070 mg.min/dL, respectively, p = 0.12). However, the insulin AUC was
      significantly lower with the BB compared to the GEL control (6485 vs. 8245
      uU.min/mL, p = 0.0002), and HOMA-IR improved with BB (p = 0.0318). Blackberry
      consumption may promote increased fat oxidation and improved insulin sensitivity
      in overweight or obese males fed a high fat diet.

PMID- 30096879
TI  - Sanger and Next Generation Sequencing Approaches to Evaluate HIV-1 Virus in Blood
      Compartments.
AB  - The implementation of antiretroviral treatment combined with the monitoring of
      drug resistance mutations improves the quality of life of HIV-1 positive
      patients. The drug resistance mutation patterns and viral genotypes are currently
      analyzed by DNA sequencing of the virus in the plasma of patients. However, the
      virus compartmentalizes, and different T cell subsets may harbor distinct viral
      subsets. In this study, we compared the patterns of HIV distribution in cell-free
      (blood plasma) and cell-associated viruses (peripheral blood mononuclear cells,
      PBMCs) derived from ART-treated patients by using Sanger sequencing- and Next
      Generation sequencing-based HIV assay. CD4+CD45RA-RO+ memory T-cells were
      isolated from PBMCs using a BD FACSAria instrument. HIV pol (protease and reverse
      transcriptase) was RT-PCR or PCR amplified from the plasma and the T-cell subset,
      respectively. Sequences were obtained using Sanger sequencing and Next-Generation
      Sequencing (NGS). Sanger sequences were aligned and edited using RECall software
      (beta v3.03). The Stanford HIV database was used to evaluate drug resistance
      mutations. Illumina MiSeq platform and HyDRA Web were used to generate and
      analyze NGS data, respectively. Our results show a high correlation between
      Sanger sequencing and NGS results. However, some major and minor drug resistance
      mutations were only observed by NGS, albeit at different frequencies. Analysis of
      low-frequency drugs resistance mutations and virus distribution in the blood
      compartments may provide information to allow a more sustainable response to
      therapy and better disease management.

PMID- 30096880
TI  - Neutralizing Epitopes and Residues Mediating the Potential Antigenic Drift of the
      Hemagglutinin-Esterase Protein of Influenza C Virus.
AB  - We mapped the hemagglutinin-esterase (HE) antigenic epitopes of the influenza C
      virus on the three-dimensional (3D) structure of the HE glycoprotein using 246
      escape mutants that were selected by a panel of nine anti-HE monoclonal
      antibodies (MAbs), including seven of the C/Ann Arbor/1/50 virus and two of the
      C/Yamagata/15/2004 virus. The frequency of variant selection in the presence of
      anti-HE MAbs was very low, with frequencies ranging from 10-4.62 to 10-7.58 for
      the C/Ann Arbor/1/50 virus and from 10-7.11 to 10-9.25 for the C/Yamagata/15/2004
      virus. Sequencing of mutant HE genes revealed 25 amino acid substitutions at 16
      positions in three antigenic sites: A-1, A-2, and A-3, and a newly designated Y-1
      site. In the 3D structure, the A-1 site was widely located around the receptor
      binding site, the A-2 site was near the receptor-destroying enzyme site, and the
      Y-1 site was located in the loop on the topside of HE. The hemagglutination
      inhibition reactions of the MAbs with influenza C viruses, circulating between
      1947 and 2016, were consistent with the antigenic-site amino acid changes. We
      also found some amino acid variations in the antigenic site of recently
      circulating strains with antigenic changes, suggesting that viruses that have the
      potential to alter antigenicity continue to circulate in humans.

PMID- 30096881
TI  - Prescribing Target Running Intensities for High-School Athletes: Can Forward and
      Backward Running Performance Be Autoregulated?
AB  - Target running intensities are prescribed to enhance sprint-running performance
      and progress injured athletes back into competition, yet is unknown whether
      running speed can be achieved using autoregulation. This study investigated the
      consistency of running intensities in adolescent athletes using autoregulation to
      self-select velocity. Thirty-four boys performed 20 m forward running (FR) and
      backward running (BR) trials at slow, moderate and fast intensities (40-55%, 60
      75% and +90% maximum effort, respectively) on three occasions. Absolute and
      relative consistency was assessed using the coefficient of variation (CV) and
      intraclass correlation coefficients (ICC). Systematic changes in 10 and 20 m
      performance were identified between trials 1-2 for moderate and fast BR (p <=
      0.01) and during moderate BR over 20 m across trials 2-3 (p <= 0.05). However,
      comparisons between trials 2-3 resulted in low typical percentage error (CV <=
      4.3%) and very good to excellent relative consistency (ICC >= 0.87) for all
      running speeds and directions. Despite FR being significantly (p <= 0.01) faster
      than BR at slow (26%), moderate (28%) and fast intensities (26%), consistency was
      similar in both running directions and strongest at the fastest speeds. Following
      appropriate familiarization, youth athletes may use autoregulation to self-select
      prescribed FR and BR target running intensities.

PMID- 30096884
TI  - Three-Dimensional Hierarchical Porous Structure of PPy/Porous-Graphene to
      Encapsulate Polysulfides for Lithium/Sulfur Batteries.
AB  - Herein, we demonstrate the fabrication of a three-dimensional (3D) polypyrrole
      coated-porous graphene (PPy/PG) composite through in-situ polymerization of
      pyrrole monomer on PG surface. The PPy/PG displays a 3D hierarchical porous
      structure and the resulting PPy/PG hybrid serves as a conductive trap to lithium
      polysulfides enhancing the electrochemical performances. Owing to the superior
      conductivity and peculiar structure, a high initial discharge capacity of 1020
      mAh g-1 and the reversible capacity of 802 mAh g-1 over 200 cycles are obtained
      for the S/PPy/PG cathode at 0.1 C, remaining the remarkable cyclic stability. In
      addition, the S/PPy/PG cathodes demonstrate an excellent rate performance
      exhibiting 477 mAh g-1 at 2 C.

PMID- 30096883
TI  - Dairy Intake and Acne Vulgaris: A Systematic Review and Meta-Analysis of 78,529
      Children, Adolescents, and Young Adults.
AB  - A meta-analysis can help inform the debate about the epidemiological evidence on
      dairy intake and development of acne. A systematic literature search of PubMed
      from inception to 11 December 2017 was performed to estimate the association of
      dairy intake and acne in children, adolescents, and young adults in observational
      studies. We estimated the pooled random effects odds ratio (OR) (95% CI),
      heterogeneity (I2-statistics, Q-statistics), and publication bias. We included 14
      studies (n = 78,529; 23,046 acne-cases/55,483 controls) aged 7-30 years. ORs for
      acne were 1.25 (95% CI: 1.15-1.36; p = 6.13 * 10-8) for any dairy, 1.22 (1.08
      1.38; p = 1.62 * 10-3) for full-fat dairy, 1.28 (1.13-1.44; p = 8.23 * 10-5) for
      any milk, 1.22 (1.06-1.41; p = 6.66 * 10-3) for whole milk, 1.32 (1.16-1.52; p =
      4.33 * 10-5) for low-fat/skim milk, 1.22 (1.00-1.50; p = 5.21 * 10-2) for cheese,
      and 1.36 (1.05-1.77; p = 2.21 * 10-2) for yogurt compared to no intake. ORs per
      frequency of any milk intake were 1.24 (0.95-1.62) by 2-6 glasses per week, 1.41
      (1.05-1.90) by 1 glass per day, and 1.43 (1.09-1.88) by >=2 glasses per day
      compared to intake less than weekly. Adjusted results were attenuated and
      compared unadjusted. There was publication bias (p = 4.71 * 10-3), and
      heterogeneity in the meta-analyses were explained by dairy and study
      characteristics. In conclusion, any dairy, such as milk, yogurt, and cheese, was
      associated with an increased OR for acne in individuals aged 7-30 years. However,
      results should be interpreted with caution due to heterogeneity and bias across
      studies.

PMID- 30096885
TI  - Genetic and Physio-Biochemical Characterization of a Novel Premature Senescence
      Leaf Mutant in Rice (Oryza sativa L.).
AB  - Premature senescence greatly affects the yield production and the grain quality
      in plants, although the molecular mechanisms are largely unknown. Here, we
      identified a novel rice premature senescence leaf 85 (psl85) mutant from ethyl
      methane sulfonate (EMS) mutagenesis of cultivar Zhongjian100 (the wild-type, WT).
      The psl85 mutant presented a distinct dwarfism and premature senescence leaf
      phenotype, starting from the seedling stage to the mature stage, with decreasing
      level of chlorophyll and degradation of chloroplast, declined photosynthetic
      capacity, increased content of malonaldehyde (MDA), upregulated expression of
      senescence-associated genes, and disrupted reactive oxygen species (ROS)
      scavenging system. Moreover, endogenous abscisic acid (ABA) level was
      significantly increased in psl85 at the late aging phase, and the detached leaves
      of psl85 showed more rapid chlorophyll deterioration than that of WT under ABA
      treatment, indicating that PSL85 was involved in ABA-induced leaf senescence.
      Genetic analysis revealed that the premature senescence leaf phenotype was
      controlled by a single recessive nuclear gene which was finally mapped in a 47 kb
      region on the short arm of chromosome 7, covering eight candidate open reading
      frames (ORFs). No similar genes controlling a premature senescence leaf phenotype
      have been identified in the region, and cloning and functional analysis of the
      gene is currently underway.

PMID- 30096882
TI  - Oxidative Stress in Methylmercury-Induced Cell Toxicity.
AB  - Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits
      significant toxicity in humans. The accumulation of MeHg through the daily
      consumption of large predatory fish poses potential health risks, and the central
      nervous system (CNS) is the primary target of toxicity. Despite well-described
      neurobehavioral effects (i.e., motor impairment), the mechanisms of MeHg-induced
      toxicity are not completely understood. However, several lines of evidence point
      out the oxidative stress as an important molecular mechanism in MeHg-induced
      intoxication. Indeed, MeHg is a soft electrophile that preferentially interacts
      with nucleophilic groups (mainly thiols and selenols) from proteins and low
      molecular-weight molecules. Such interaction contributes to the occurrence of
      oxidative stress, which can produce damage by several interacting mechanisms,
      impairing the function of various molecules (i.e., proteins, lipids, and nucleic
      acids), potentially resulting in modulation of different cellular signal
      transduction pathways. This review summarizes the general aspects regarding the
      interaction between MeHg with regulators of the antioxidant response system that
      are rich in thiol and selenol groups such as glutathione (GSH), and the
      selenoenzymes thioredoxin reductase (TrxR) and glutathione peroxidase (Gpx). A
      particular attention is directed towards the role of the PI3K/Akt signaling
      pathway and the nuclear transcription factor NF-E2-related factor 2 (Nrf2) in
      MeHg-induced redox imbalance.

PMID- 30096886
TI  - Study of the Influence of Shielding Gases on Laser Metal Deposition of Inconel
      718 Superalloy.
AB  - The use of the Laser Metal Deposition (LMD) technology as a manufacturing and
      repairing technique in industrial sectors like the die and mold and aerospace is
      increasing within the last decades. Research carried out in the field of LMD
      process situates argon as the most usual inert gas, followed by nitrogen. Some
      leading companies have started to use helium and argon as carrier and shielding
      gas, respectively. There is therefore a pressing need to know how the use of
      different gases may affect the LMD process due there being a lack of knowledge
      with regard to gas mixtures. The aim of the present work is to evaluate the
      influence of a mixture of argon and helium on the LMD process by analyzing single
      tracks of deposited material. For this purpose, special attention is paid to the
      melt pool temperature, as well as to the characterization of the deposited clads.
      The increment of helium concentration in the gases of the LMD processes based on
      argon will have three effects. The first one is a slight reduction of the height
      of the clads. Second, an increase of the temperature of the melt pool. Last,
      smaller wet angles are obtained for higher helium concentrations.

PMID- 30096887
TI  - New Chromones from a Marine-Derived Fungus, Arthrinium sp., and Their Biological
      Activity.
AB  - Five new chromone derivatives, arthones A-E (1-5), together with eight known
      biogenetically related cometabolites (6-13), were isolated from a deep-sea
      derived fungus Arthrinium sp. UJNMF0008. Their structures were assigned by
      detailed analyses of spectroscopic data, while the absolute configurations of 1
      and 5 were established by electronic circular dichroism (ECD) calculations and
      that of 2 was determined by modified Mosher ester method. Compounds 3 and 8
      exhibited potent antioxidant property with DPPH and ABTS radical scavenging
      activities, with IC50 values ranging from 16.9 to 18.7 MUM. Meanwhile, no
      compounds indicated obvious bioactivity in our antimicrobial and anti
      inflammatory assays at 50.0 MUM.

PMID- 30096888
TI  - An Innovative Approach to Manganese-Substituted Hydroxyapatite Coating on Zinc
      Oxide-Coated 316L SS for Implant Application.
AB  - In this paper, the synthesis of porous manganese substituted hydroxyapatite (Mn
      HAp) coating on zinc oxide (ZnO) coated stainless steel (316L SS) using the
      electrodeposition technique is reported. The structural, functional,
      morphological, and elemental analyses are characterized by various analytical
      techniques including X-ray diffraction (XRD), Fourier transform infrared
      spectroscopy (FT-IR), field emission scanning electron microscopy (FE-SEM),
      transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy
      (XPS). Results of electrochemical techniques such as cyclic polarization and
      impedance show that the Mn-HAp coating on ZnO coated 316L SS has the highest
      corrosion resistance in simulated body fluid (SBF) solution. Moreover,
      dissolution of metal ions was extremely reduced, as evaluated by inductively
      coupled plasma-atomic emission spectroscopy (ICP-AES). The adhesion and hardness
      of Mn-HAp/ZnO bilayer coatings have superior mechanical properties over
      individual coatings. Further, the biocompatibility of in vitro osteoblast
      attachment, cell viability, and live/dead assessment also confirmed the
      suitability of Mn-HAp/ZnO bilayer coating on 316L SS for orthopedic applications.

PMID- 30096889
TI  - Treatment of Periodontal Ligament Stem Cells with MOR and CBD Promotes Cell
      Survival and Neuronal Differentiation via the PI3K/Akt/mTOR Pathway.
AB  - Periodontal ligament mesenchymal stem cells (hPDLSCs), as well as all mesenchymal
      stem cells, show self-renewal, clonogenicity, and multi-tissue differentiation
      proprieties and can represent a valid support for regenerative medicine. We
      treated hPDLSCs with a combination of Moringin (MOR) and Cannabidiol (CBD), in
      order to understand if treatment could improve their survival and their in vitro
      differentiation capacity. Stem cells survival is fundamental to achieve a
      successful therapy outcome in the re-implanted tissue of patients. Through NGS
      transcriptome analysis, we found that combined treatment increased hPDLSCs
      survival, by inhibition of apoptosis as demonstrated by enhanced expression of
      anti-apoptotic genes and reduction of pro-apoptotic ones. Moreover, we
      investigated the possible involvement of PI3K/Akt/mTOR pathway, emphasizing a
      differential gene expression between treated and untreated cells. Furthermore,
      hPDLSCs were cultured for 48 h in the presence or absence of CBD and MOR and,
      after confirming the cellular viability through MTT (3-(4,5-dimethylthiazolyl-2)
      2,5-diphenyltetrazoliumbromide) assay, we examined the presence of neuronal
      markers, through immunofluorescence analysis. We found an increased expression of
      Nestin and GAP43 (growth associated protein 43) in treated cells. In conclusion,
      hPDLSCs treated with Moringin and Cannabidiol showed an improved survival
      capacity and neuronal differentiation potential.

PMID- 30096891
TI  - A Sensor Image Dehazing Algorithm Based on Feature Learning.
AB  - To solve the problems of color distortion and structure blurring in images
      acquired by sensors during bad weather, an image dehazing algorithm based on
      feature learning is put forward to improve the quality of sensor images. First,
      we extracted the multiscale structure features of the haze images by sparse
      coding and the various haze-related color features simultaneously. Then, the
      generative adversarial network (GAN) was used for sample training to explore the
      mapping relationship between different features and the scene transmission.
      Finally, the final haze-free image was obtained according to the degradation
      model. Experimental results show that the method has obvious advantages in its
      detail recovery and color retention. In addition, it effectively improves the
      quality of sensor images.

PMID- 30096890
TI  - Comorbidity of Physical and Anxiety Symptoms in Adolescent: Functional
      Impairment, Self-Rated Health and Subjective Well-Being.
AB  - Physical disorders and anxiety are frequently comorbid. This study investigates
      the characteristics of physical disorders, self-rated heath, subjective well
      being and anxiety in adolescents. Data were drawn from the Saving and Empowering
      Young Lives in Europe cohort study. From 11 countries 11,230 adolescents, aged 14
      16 years were included. Zung Self-Rating Anxiety Scale (SAS), WHO-5 Well-Being
      Index and five questions prepared for this study to evaluate physical illnesses
      and self-rated heath were administered. Anxiety levels were significantly higher
      in adolescents who reported having physical disability (p < 0.001, Cohen's d =
      0.40), suffering from chronic illnesses (p < 0.001, Cohen's d = 0.40),
      impairments associated to health conditions (p < 0.001, Cohen's d = 0.61), or
      reported poor to very poor self-rated health (p < 0.001, Cohen's d = 1.11).
      Mediational analyses revealed no direct effect of having a chronic
      illness/physical disability on subjective well-being, but the indirect effects
      through higher levels of anxiety were significant. Functional impairment related
      to health conditions was both directly and indirectly (through higher levels of
      anxiety) associated with lower well-being. The co-occurrence of anxiety and
      physical disorders may confer a greater level of disability and lower levels of
      subjective well-being. Clinicians have to screen anxiety, even in a subthreshold
      level in patients with choric physical illness or with medically unexplained
      physical symptoms.

PMID- 30096892
TI  - Food Sources of Energy and Nutrients of Public Health Concern and Nutrients to
      Limit with a Focus on Milk and other Dairy Foods in Children 2 to 18 Years of
      Age: National Health and Nutrition Examination Survey, 2011-2014.
AB  - Many children are not meeting current nutrient recommendations. The objective of
      this study was to determine the food sources of energy, nutrients of public
      health concern, and nutrients to limit with a focus on dairy foods. Twenty-four
      hour dietary recall data from children 2-5 (n = 1511), 6-11 (n = 2193), and 12-18
      years (n = 2172) participating in NHANES 2011-2014 were analyzed. Energy, fiber,
      calcium, potassium, vitamin D, added sugars, saturated fatty acids (SFA), and
      sodium intakes were sample-weighted and ranked on percentage contribution to the
      diet using specific food group intake and disaggregated data for dairy foods. For
      children 2-5, 6-11, and 12-18 years, milk, sweet bakery products, and sweetened
      beverages, respectively were the top food sources of energy, respectively. For
      calcium, potassium, and vitamin D, milk was the top ranked food source in all age
      groups. For children 2-5, 6-11, and 12-18 years, milk, sweet bakery products, and
      pizza, respectively were the top three ranked food sources of SFA; and sugar
      sweetened beverages and sweet bakery products were to top two food group sources
      of added sugars. Cured meats/poultry, pizza, and pizza, respectively, were the
      top ranked food sources of sodium for the three age groups. Identification of
      food sources of these nutrients can help health professionals implement
      appropriate dietary recommendations and plan age-appropriate interventions.

PMID- 30096893
TI  - Synthesis of Amorphous InSb Nanowires and a Study of the Effects of Laser
      Radiation and Thermal Annealing on Nanowire Crystallinity.
AB  - Although various synthesis and characterization strategies have been employed for
      the synthesis of crystalline nanowires, there is very little work done on
      development of low-dimensional amorphous semiconductors. This paper presents a
      simple strategy to grow amorphous InSb (a-InSb) nanowires (NWs) in a chemical
      vapor deposition (CVD) system. The NWs were grown on Si substrate coated with
      indium film and the lack of crystallinity in the as-grown stoichiometric NWs was
      ascertained by Raman spectroscopy and electron transport measurements. A model
      proposed to explain the amorphous NW growth mechanism takes into account the fact
      that NW growth was carried out at the high temperature ramp-up rate of 75 ?C/min.
      This high rate is believed to affect the growth kinematics and determine the
      arrangement of atoms in the growing NW. Raman spectrum of the as-grown sample
      shows a broad peak around 155 cm-1, indicative of the presence of high density of
      homopolar Sb-Sb bonds in the amorphous matrix. It was also found that high
      intensity laser light induces localized crystallization of the NW, most likely
      due to radiation-stimulated diffusion of defects in a-InSb. The nonlinear trend
      of the current-voltage characteristics for individually contacted a-InSb NWs was
      analyzed to prove that the non-linearity is not induced by Schottky contacts. At
      high bias fields, space charge limited conduction was the proposed electron
      transport mechanism. Post-growth annealing of the as-grown a-InSb NWs was found
      to be very effective in causing the NWs to undergo a phase transition from
      amorphous to crystalline.

PMID- 30096894
TI  - Transmission of Influenza A in a Student Office Based on Realistic Person-to
      Person Contact and Surface Touch Behaviour.
AB  - Influenza A viruses result in the deaths of hundreds of thousands of individuals
      worldwide each year. In this study, influenza A transmission in a graduate
      student office is simulated via long-range airborne, fomite, and close contact
      routes based on real data from more than 3500 person-to-person contacts and
      127,000 surface touches obtained by video-camera. The long-range airborne, fomite
      and close contact routes contribute to 54.3%, 4.2% and 44.5% of influenza A
      infections, respectively. For the fomite route, 59.8%, 38.1% and 2.1% of viruses
      are transmitted to the hands of students from private surfaces around the
      infected students, the students themselves and other susceptible students,
      respectively. The intranasal dose via fomites of the students' bodies,
      belongings, computers, desks, chairs and public facilities are 8.0%, 6.8%, 13.2%,
      57.8%, 9.3% and 4.9%, respectively. The intranasal dose does not monotonously
      increase or decrease with the virus transfer rate between hands and surfaces.
      Mask wearing is much more useful than hand washing for control of influenza A in
      the tested office setting. Regular cleaning of high-touch surfaces, which can
      reduce the infection risk by 2.14%, is recommended and is much more efficient
      than hand-washing.

PMID- 30096896
TI  - Comparative Analysis of Transcriptomes to Identify Genes Associated with Fruit
      Size in the Early Stage of Fruit Development in Pyrus pyrifolia.
AB  - Pear (Pyrus L.) is an important commercial fruit in the world. The fruit size is
      one of the important characters in fruit quality. The previous research reported
      that the fruit size of pear was mainly caused by the number of cell in about 40
      days after blossom (DAB) in nature. However, studies about the mechanisms
      underlying cell division in young fruit development are very limited in pear. Two
      pear accessions codenamed 'GH59B' with big fruit and 'GH81S' with small fruit in
      three stages were sampled and the RNA-seq high-throughput sequencing was used to
      evaluate changes of gene transcription levels in the early stage of fruit
      development. The difference of cell size among two samples was little in 40 DAB,
      implying that the difference of the fruit size was caused by the number of the
      cell. More than 274,517,982 high quality reads from six libraries of fruit
      development were sequenced. A total of 797 differentially expressed genes (DEGs)
      were identified. Three cytokinin dehydrogenase genes and two gibberellin 2-beta
      dioxygenase gene were identified in the Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathways related to zeatin and gibberellin. Their expression was
      upregulated at 20 DAB in 'GH81S' and at 30 DAB in 'GH59B', suggesting that the
      small fruit size might be related to the early degradation of cytokinin and
      gibberellin inducing a short period of cell division. A total of 38 DEGs of
      transcription factors were found and 23 DEGs including NAC, ERF and bHLH
      transcription factors were highly related with cytokinin dehydrogenase and
      gibberellin dioxygenase genes. Altogether, the results of the present study
      provide information from a comprehensive gene expression analysis and insight
      into the molecular mechanism underlying the difference of fruit size in Pyrus
      pyrifolia.

PMID- 30096895
TI  - Recent Advances in Scanning Electrochemical Microscopy for Biological
      Applications.
AB  - Scanning electrochemical microscopy (SECM) is a chemical microscopy technique
      with high spatial resolution for imaging sample topography and mapping specific
      chemical species in liquid environments. With the development of smaller, more
      sensitive ultramicroelectrodes (UMEs) and more precise computer-controlled
      measurements, SECM has been widely used to study biological systems over the past
      three decades. Recent methodological breakthroughs have popularized SECM as a
      tool for investigating molecular-level chemical reactions. The most common
      applications include monitoring and analyzing the biological processes associated
      with enzymatic activity and DNA, and the physiological activity of living cells
      and other microorganisms. The present article first introduces the basic
      principles of SECM, followed by an updated review of the applications of SECM in
      biological studies on enzymes, DNA, proteins, and living cells. Particularly, the
      potential of SECM for investigating bacterial and biofilm activities is
      discussed.

PMID- 30096897
TI  - Xenotropic Mouse Gammaretroviruses Isolated from Pre-Leukemic Tissues Include a
      Recombinant.
AB  - Naturally-occurring lymphomagenesis is induced by mouse leukemia viruses (MLVs)
      carried as endogenous retroviruses (ERVs). Replicating the ecotropic MLVs
      recombines with polytropic (P-ERVs) and xenotropic ERVs (X-ERVs) to generate
      pathogenic viruses with an altered host range. While most recovered nonecotropic
      recombinants have a polytropic host range, the X-MLVs are also present in the pre
      leukemic tissues. We analyzed two such isolates from the AKR mice to identify
      their ERV progenitors and to look for evidence of recombination. AKR40 resembles
      the active X-ERV Bxv1, while AKR6 has a Bxv1-like backbone with substitutions
      that alter the long terminal repeat (LTR) enhancer and the envelope (env). AKR6
      has a modified xenotropic host range, and its Env residue changes all lie outside
      of the domain that governs the receptor choice. The AKR6 segment spanning the two
      substitutions, but not the entire AKR6 env-LTR, exists as an ERV, termed Xmv67,
      in AKR, but not in the C57BL/6 mice. This suggests that AKR6 is the product of
      one, not two, recombination events. Xmv67 originated in the Asian mice. These
      data indicate that the recombinant X-MLVs that can be generated during
      lymphomagenesis, describe a novel X-ERV subtype found in the AKR genome, but not
      in the C57BL/6 reference genome, and identify residues in the envelope C-terminus
      that may influence the host range.

PMID- 30096898
TI  - Effects of Regulated Deficit Irrigation on Amino Acid Profiles and Their Derived
      Volatile Compounds in Cabernet Sauvignon (Vitis vinifera L.) Grapes and Wines.
AB  - Amino acid contents and their derived volatile compositions in Cabernet Sauvignon
      grapes and wines after regulated deficit irrigation (RDI) were investigated
      during the 2015 and 2016 growing seasons in Yinchuan (NingXia, China). High
      performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry
      (GC-MS) were used for amino acid and volatile compound analyses. Three RDI
      strategies were tested: 60% (RDI-1), 70% (RDI-2), and 80% (RDI-3) of grapevine
      estimated evapotranspiration (ETc), and 100% ETc was used as the control group
      (CK). RDI-treated vines had lower yields and berry weights with higher total
      soluble solids than the control treatment. RDI-1 increased proline levels in
      berries and wines. RDI-2 enhanced tyrosine and asparagine levels in wines. RDI-3
      enhanced arginine, alanine, valine, leucine, and isoleucine levels in berries and
      wines. RDI-2 and RDI-3 increased the concentrations of 2-methyl-1-butyl acetate,
      benzaldehyde, 3-methyl-1-pentanol, and 3-methyl-1-butanol in wines. The
      accumulation of volatile compounds was closely related to the amino acid
      concentrations-especially isoleucine, valine, and leucine-in grapes. Our results
      showed that RDI treatments altered amino acid concentrations and their derived
      volatile compositions in wines.

PMID- 30096899
TI  - Effect of Icariin on Engineered 3D-Printed Porous Scaffolds for Cartilage Repair.
AB  - In recent times, cartilage defects have been the most common athletic injuries,
      often leading to dreadful consequences such as osteoarthritis, pain, joint
      deformities, and other symptoms. It is also evident that damage to articular
      cartilage is often difficult to recover or self-heal because of poor vascular,
      nervous, and lymphatic supplies. Moreover, cartilage cells have poor regeneration
      ability and high maturity. Inspired by these facts and the rapid advances in the
      field of tissue engineering (TE), we fabricated highly porous three-dimensional
      (3D) scaffold architectures based on cell-responsive polymeric inks, i.e., sodium
      alginate and gelatin (SA-Gel, 1:3 ratio), by a novel 3D printing method.
      Moreover, the effect of various processing parameters was systematically
      investigated. The printed scaffolds of polymer composites gels with excellent
      transparency, moderate viscosity, and excellent fluid properties showed good
      surface morphology, better thermal stability and swelling effect, and unique
      interconnected porous architectures at the optimized operating parameters. In
      vitro cell proliferation experiments of these cytocompatible scaffolds showed the
      excellent adhesion rate and growth behavior of chondrocytes. In addition, the
      porous architectures facilitated the efficient distribution of cells with only a
      few remaining on the surface, which was confirmed by confocal laser scanning
      microscopic (CLSM) observations. Icariin (ICA) addition at a concentration of 10
      MUg/mL further significantly enhanced the proliferation of chondrocytes. We
      envision that these cell-responsive polymeric inks in the presence of growth
      regulators like ICA may have potential in engineering complex tissue constructs
      toward diverse applications in TE.

PMID- 30096900
TI  - Experimental and Theoretical Studies on the Adsorption Mechanisms of Uranium (VI)
      Ions on Chitosan.
AB  - An experiment on the adsorption of uranium (VI) by chitosan was conducted to
      investigate the efficiency of chitosan as an adsorbent for U(VI). The adsorption
      potential of U(VI) by chitosan was investigated with ICP-MS by varying the
      experimental conditions such as the pH in order to obtain the optimum conditions.
      Adsorption dependence on the pH was confirmed, and the highest uptake of U(VI)
      was observed at pH 5. In addition, to scrutinize the experimental results,
      quantum chemistry calculations were performed. The results, taking into account
      the experimental conditions, show that the adsorption efficiency increases as the
      total charge of the adsorbent and adsorbate species decreases if both of them are
      positively charged. It was also found that a slight change in the adsorption
      geometric configuration controls the adsorption efficiency.

PMID- 30096901
TI  - Characterization of Antibacterial Cell-Free Supernatant from Oral Care Probiotic
      Weissella cibaria, CMU.
AB  - Recently, studies have explored the use of probiotics like the Weissella cibaria
      strain, CMU (oraCMU), for use as preventive dental medicine instead of chemical
      oral care methods. The present study was conducted to investigate the
      antibacterial properties of the cell-free supernatant (CFS) from this bacterium.
      Cell morphology using the scanning electron microscope, and the antibacterial
      effect of CFS under various growth conditions were evaluated. The production of
      hydrogen peroxide, organic acids, fatty acids, and secretory proteins was also
      studied. Most of the antibacterial effects of oraCMU against periodontal
      pathogens were found to be acid- and hydrogen peroxide-dose-dependent effects.
      Lactic acid, acetic acid, and citric acid were the most common organic acids.
      Among the 37 fatty acids, only 0.02% of oleic acid (C18:1n-9, cis) was detected.
      Proteomic analysis of the oraCMU secretome identified a total of 19 secreted
      proteins, including N-acetylmuramidase. This protein may be a potential anti
      microbial agent effective against Porphyromonas gingivalis.

PMID- 30096902
TI  - Fabrication of a Urea Biosensor for Real-Time Dynamic Fluid Measurement.
AB  - In this study, a portable urea sensor that monitors the urea concentration in
      flow conditions was fabricated. We propose an electrochemical sensor that
      continually measures the urea concentration of samples flowing through it at a
      constant flow rate in real time. For the electrochemical sensing, a porous silk
      fibroin membrane with immobilized urease was mounted in a polydimethylsiloxane
      (PDMS) sensor housing. The fabricated urea sensor elicited linear current
      concentration characteristics in the clinically significant concentration range
      (0.1-20 mM) based on peritoneal dialysis. The sensor maintained the linear
      current-concentration characteristics during operation in flow conditions.

PMID- 30096903
TI  - Relative Validity of a Beverage Frequency Questionnaire Used to Assess Fluid
      Intake in the Autosomal Dominant Polycystic Kidney Disease Population.
AB  - Maintaining hydration sufficient to reduce levels of arginine vasopressin has
      been hypothesised to slow kidney cyst growth in autosomal dominant polycystic
      kidney disease (ADPKD). The semi-quantitative beverage frequency questionnaire
      (BFQ) was designed to measure usual fluid intake over the past month. The aim of
      this study was to assess the validity and reliability of the BFQ compared with
      the 24-h urine biomarkers. Participants with ADPKD (18-67 years; estimated
      glomerular filtration rate (eGFR) >= 30 mL/min1.73 m2) completed the BFQ. Serum
      creatinine, eGFR, 24-h urine volume, and osmolality were measured. Pearson
      correlation coefficients, paired t test, and Bland-Altman plots were used to
      evaluate agreement between the methods. A subset repeated the BFQ to assess
      reliability. A total of 121 participants (54% male, 43 +/- 11 years; mean +/- SD)
      completed the BFQ and at least one 24-h urine collection. The correlation between
      the BFQ and the 24-h urine volume was moderate (r = 0.580) and weaker with the 24
      h urine osmolality (r = -0.276). The Bland-Altman plots revealed good agreement
      between the BFQ and the 24-h urine volume with no obvious bias; however, the
      limits of agreement were wide (-1517-1943 mL). The BFQ1 and BFQ2 were strongly
      correlated (r = 0.799, p < 0.001) and were not significantly different (p =
      0.598). The BFQ is a valid and reliable tool to assess the usual fluid intake of
      the ADPKD population.

PMID- 30096905
TI  - The Effectiveness and Cost-Effectiveness of Screening for HIV in Migrants in the
      EU/EEA: A Systematic Review.
AB  - Migrants, defined as individuals who move from their country of origin to
      another, account for 40% of newly-diagnosed cases of human immunodeficiency virus
      (HIV) in the European Union/European Economic Area (EU/EEA). Populations at high
      risk for HIV include migrants, from countries or living in neighbourhoods where
      HIV is prevalent, and those participating in high risk behaviour. These migrants
      are at risk of low CD4 counts at diagnosis, increased morbidity, mortality, and
      onward transmission. The aim of this systematic review is to evaluate the
      effectiveness and cost-effectiveness of HIV testing strategies in migrant
      populations and to estimate their effect on testing uptake, mortality, and
      resource requirements. Following a systematic overview, we included four
      systematic reviews on the effectiveness of strategies in non-migrant populations
      and inferred their effect on migrant populations, as well as eight individual
      studies on cost-effectiveness/resource requirements. We assessed the certainty of
      our results using the Grading of Recommendations Assessment, Development, and
      Evaluation (GRADE) approach. The systematic reviews reported that HIV tests are
      highly accurate (rapid test >90% sensitivity, Western blot and ELISA >99%
      sensitivity). A meta-analysis showed that rapid testing approaches improve the
      access and uptake of testing (risk ratio = 2.95, 95% CI: 1.69 to 5.16), and were
      associated with a lower incidence of HIV in the middle-aged women subgroup among
      marginalised populations at a high risk of HIV exposure and HIV related stigma.
      Economic evidence on rapid counselling and testing identified strategic
      advantages with rapid tests. In conclusion, community-based rapid testing
      programmes may have the potential to improve uptake of HIV testing among migrant
      populations across a range of EU/EEA settings.

PMID- 30096906
TI  - Swine Influenza Virus Induces RIPK1/DRP1-Mediated Interleukin-1 Beta Production.
AB  - Nucleotide-binding domain and leucine-rich repeat-containing protein 3 (NLRP3)
      inflammasome plays a pivotal role in modulating lung inflammation in response to
      the influenza A virus infection. We previously showed that the swine influenza
      virus (SIV) infection induced NLRP3 inflammasome-mediated IL-1beta production in
      primary porcine alveolar macrophages (PAMs), and we were interested in examining
      the upstream signaling events that are involved in this process. Here, we report
      that the SIV-infection led to dynamin-related protein 1 (DRP1) phosphorylation at
      serine 579 and mitochondrial fission in PAMs. IL-1beta production was dependent
      on the reactive oxygen species (ROS) production, and DRP1 phosphorylation
      resulted in the upregulation of the NLRP3 inflammasome. Furthermore, the
      requirement of the kinase activity of receptor-interacting protein kinase 1
      (RIPK1) for the IL-1beta production and RIPK1-DRP1 association suggested that
      RIPK1 is an upstream kinase for DRP1 phosphorylation. Our results reveal a
      critical role of the RIPK1/DRP1 signaling axis, whose activation leads to
      mitochondrial fission and ROS release, in modulating porcine NLRP3 inflammasome
      mediated IL-1beta production in SIV-infected PAMs.

PMID- 30096907
TI  - Changes in Hypertension-Related Knowledge and Behavior and Their Associations
      with Socioeconomic Status among Recently Urbanized Residents in China: 2013-2016.
AB  - The rapid urbanization in China has brought with it some health benefits, but it
      also brought about a negative influence on the lifestyle of residents. We
      conducted this study to assess the change in hypertension-related knowledge and
      behavior from 2013 to 2016 among recently urbanized residents and determine their
      association with socioeconomic status (SES). This research used data from two
      cross-sectional studies conducted in Hezuo community in Chengdu, Sichuan province
      of China. A total of 2268 and 2601 individuals, respectively, participated and
      completed standard questionnaires. According to the results, the median (IQR)
      scores of health knowledge was 1 (0,3) and 3 (1,5), respectively, (p < 0.001) and
      the median (IQR) scores of health behavior was 6 (5,6) and 5 (5,6), respectively,
      (p < 0.001) in 2013 and 2016. The rate of sufficient knowledge increased from
      8.8% to 18.1% (p < 0.001), while the rate of correct behavior decreased from
      54.5% to 45.5% (p < 0.001) in three years. Logistic regression analysis showed
      that higher education was associated with sufficient hypertension-related
      knowledge (p < 0.05), and those with higher education, unemployment, and
      retirement were more likely to have sufficient behavior (p < 0.05). The impact of
      SES on knowledge was stable between 2013 and 2016. The behavior difference
      between the middle school educated and the illiterate increased from 2013 to 2016
      (p < 0.05), and the behavior difference between the unemployed and manual workers
      decreased from 2013 to 2016 (p < 0.05). Our results revealed that hypertension
      related knowledge improved with no corresponding improvement in self-reported
      behavior among recently urbanized residents from 2013 to 2016. Organizational
      strategy should be implemented to improve health education on knowledge, and what
      is more, translate knowledge into behavior. All these measures should be given
      more attention to the lower educated and manual workers among recently urbanized
      residents to eliminate the SES disparity.

PMID- 30096904
TI  - Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection.
AB  - Marine biotoxins are produced by aquatic microorganisms and accumulate in
      shellfish or finfish following the food web. These toxins usually reach human
      consumers by ingestion of contaminated seafood, although other exposure routes
      like inhalation or contact have also been reported and may cause serious illness.
      This review shows the current data regarding the symptoms of acute intoxication
      for several toxin classes, including paralytic toxins, amnesic toxins,
      ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and
      palytoxins. The information available about chronic toxicity and relative potency
      of different analogs within a toxin class are also reported. The gaps of
      toxicological knowledge that should be studied to improve human health protection
      are discussed. In general, gathering of epidemiological data in humans, chronic
      toxicity studies and exploring relative potency by oral administration are
      critical to minimize human health risks related to these toxin classes in the
      near future.

PMID- 30096909
TI  - IgA Deficiency and Nephrotic Syndrome in Children.
AB  - Background: Imunoglobulin A (IgA) deficiency (IgAD) is the most common form of
      primary immunodeficiency in Western countries. There have been several reports on
      IgAD complicated by glomerulonephritis in adults, but only very few cases of IgAD
      with nephropathy have been reported in children. We present two cases of IgAD
      with relapsing nephrotic syndrome in pediatric age. Case presentation: A 4-year
      old boy and a 2-year-old boy presented with bilateral periorbital oedema and
      weight gain. The results of laboratory tests revealed IgAD (IgA < 7 mg/dL),
      normal creatinine, hypoprotidaemia, hypoalbuminaemia, and nephrotic proteinuria.
      A diagnosis of IgAD and idiopathic nephrotic syndrome was made, and steroid
      treatment (prednisone 60 mg/mq/day) was started. During steroid tapering, the
      children experienced several relapses and to obtain a positive outcome they
      required therapy with human monoclonal anti-CD20 antibodies (rituximab in the
      first child, ofatumumab in the second one). Conclusions: Our cases highlight that
      IgAD can be observed in nephrotic syndrome and nephropathy in children with IgAD
      appears to be complicated and difficult to treat with corticosteroids alone.
      Further research is needed to better describe the clinical manifestations and
      pathological pictures among subjects with IgAD and nephrotic syndrome to
      understand whether IgAD has a prognostic value in children with nephrotic
      syndrome and to let clinical physicians define a more personalized and
      appropriate approach for the management of these patients.

PMID- 30096908
TI  - Mesenchymal Stem Cell Migration during Bone Formation and Bone Diseases Therapy.
AB  - During bone modeling, remodeling, and bone fracture repair, mesenchymal stem
      cells (MSCs) differentiate into chondrocyte or osteoblast to comply bone
      formation and regeneration. As multipotent stem cells, MSCs were used to treat
      bone diseases during the past several decades. However, most of these
      implications just focused on promoting MSC differentiation. Furthermore, cell
      migration is also a key issue for bone formation and bone diseases treatment.
      Abnormal MSC migration could cause different kinds of bone diseases, including
      osteoporosis. Additionally, for bone disease treatment, the migration of
      endogenous or exogenous MSCs to bone injury sites is required. Recently,
      researchers have paid more and more attention to two critical points. One is how
      to apply MSC migration to bone disease therapy. The other is how to enhance MSC
      migration to improve the therapeutic efficacy of bone diseases. Some considerable
      outcomes showed that enhancing MSC migration might be a novel trick for reversing
      bone loss and other bone diseases, such as osteoporosis, fracture, and
      osteoarthritis (OA). Although plenty of challenges need to be conquered,
      application of endogenous and exogenous MSC migration and developing different
      strategies to improve therapeutic efficacy through enhancing MSC migration to
      target tissue might be the trend in the future for bone disease treatment.

PMID- 30096911
TI  - Nontargeted Metabolomics for Phenolic and Polyhydroxy Compounds Profile of Pepper
      (Piper nigrum L.) Products Based on LC-MS/MS Analysis.
AB  - In the present study, nontargeted metabolomics was used to screen the phenolic
      and polyhydroxy compounds in pepper products. A total of 186 phenolic and
      polyhydroxy compounds, including anthocyanins, proanthocyanidins, catechin
      derivatives, flavanones, flavones, flavonols, isoflavones and 3-O-p-coumaroyl
      quinic acid O-hexoside, quinic acid (polyhydroxy compounds), etc. For the
      selected 50 types of phenolic compound, except malvidin 3,5-diglucoside (malvin),
      l-epicatechin and 4'-hydroxy-5,7-dimethoxyflavanone, other compound contents were
      present in high contents in freeze-dried pepper berries, and pinocembrin was
      relatively abundant in two kinds of pepper products. The score plots of principal
      component analysis indicated that the pepper samples can be classified into four
      groups on the basis of the type pepper processing. This study provided a
      comprehensive profile of the phenolic and polyhydroxy compounds of different
      pepper products and partly clarified the factors responsible for different
      metabolite profiles in ongoing studies and the changes of phenolic compounds for
      the browning mechanism of black pepper.

PMID- 30096910
TI  - The Effects of Synthetically Modified Natural Compounds on ABC Transporters.
AB  - Multidrug resistance (MDR) is a major hurdle which must be overcome to
      effectively treat cancer. ATP-binding cassette transporters (ABC transporters)
      play pivotal roles in drug absorption and disposition, and overexpression of ABC
      transporters has been shown to attenuate cellular/tissue drug accumulation and
      thus increase MDR across a variety of cancers. Overcoming MDR is one desired
      approach to improving the survival rate of patients. To date, a number of
      modulators have been identified which block the function and/or decrease the
      expression of ABC transporters, thereby restoring the efficacy of a range of
      anticancer drugs. However, clinical MDR reversal agents have thus far proven
      ineffective and/or toxic. The need for new, effective, well-tolerated and
      nontoxic compounds has led to the development of natural compounds and their
      derivatives to ameliorate MDR. This review evaluates whether synthetically
      modifying natural compounds is a viable strategy to generate potent, nontoxic,
      ABC transporter inhibitors which may potentially reverse MDR.

PMID- 30096912
TI  - Differential and Interactive Effects of Substrate Topography and Chemistry on
      Human Mesenchymal Stem Cell Gene Expression.
AB  - Variations in substrate chemistry and the micro-structure were shown to have a
      significant effect on the biology of human mesenchymal stromal cells (hMSCs).
      This occurs when differences in the surface properties indirectly modulate
      pathways within numerous signaling networks that control cell fate. To understand
      how the surface features affect hMSC gene expression, we performed RNA-sequencing
      analysis of bone marrow-derived hMSCs cultured on tissue culture-treated
      polystyrene (TCP) and poly(l-lactide) (PLLA) based substrates of differing
      topography (Fl: flat and Fs: fibrous) and chemistry (Pr: pristine and Am:
      aminated). Whilst 80% of gene expression remained similar for cells cultured on
      test substrates, the analysis of differentially expressed genes (DEGs) revealed
      that surface topography significantly altered gene expression more than surface
      chemistry. The Fl and Fs topologies introduced opposite directional alternations
      in gene expression when compared to TCP control. In addition, the effect of
      chemical treatment interacted with that of topography in a synergistic manner
      with the Pr samples promoting more DEGs than Am samples in all gene ontology
      function groups. These findings not only highlight the significance of the
      culture surface on regulating the overall gene expression profile but also
      provide novel insights into cell-material interactions that could help further
      design the next-generation biomaterials to facilitate hMSC applications. At the
      same time, further studies are required to investigate whether or not the
      observations noted correlate with subsequent protein expression and functionality
      of cells.

PMID- 30096913
TI  - Evaluating Whole Grain Intervention Study Designs and Reporting Practices Using
      Evidence Mapping Methodology.
AB  - Consumption of whole grains have been associated with reduced risk of chronic
      diseases in many observational studies; yet, results of intervention studies are
      mixed. We aimed to use evidence mapping to capture the methodological and
      reporting variability in whole grain intervention studies that may contribute to
      this inconsistency. We conducted a reproducible search in OVID Medline for whole
      grain human intervention studies (published 1946 to February 2018). After
      screening based on a priori criteria, we identified 202 publications describing a
      total of 213 unique trials. Over half (55%) were acute trials, lasting <=1 day,
      30% were moderate duration studies (up to 6 weeks) and 15% were of longer
      duration (more than 6 weeks). The majority of acute trials (75%) examined
      measures of glycaemia and/or insulinemia, while most of the longer trials
      included measures of cardiometabolic health (71%), appetite/satiety (57%) and
      weight/adiposity (56%). Among the moderate and long duration trials, there was a
      wide range of how whole grains were described but only 10 publications referenced
      an established definition. Only 55% of trials reported the actual amount of whole
      grains (in grams or servings), while 36% reported the amount of food/product and
      9% did not report a dose at all. Of the interventions that provided a mixture of
      whole grains, less than half (46%) reported the distribution of the different
      grain types. Reporting of subject compliance also varied and only 22% used
      independent biomarkers of whole grain intake. This evidence map highlights the
      need to standardize both study protocols and reporting practices to support
      effective synthesis of study results and provide a stronger foundation to better
      inform nutrition scientists and public health policy.

PMID- 30096916
TI  - Development of a Geospatial Data-Based Methodology for Stormwater Management in
      Urban Areas Using Freely-Available Software.
AB  - Intense urbanisation, combined with climate change impacts such as increased
      rainfall intensity, is overloading conventional drainage systems, increasing the
      number of combined sewer overflow events and making treatment plants outdated.
      There is a need for better urban planning, incorporating stormwater and flood
      management design in order to accurately design urban drainage networks.
      Geographic Information System (GIS) tools are capable of identifying and
      delineating the runoff flow direction, as well as accurately defining small-sized
      urban catchments using geospatial data. This study explores the synergies between
      GIS and stormwater management design tools for better land-use planning,
      providing a new methodology which has the potential to incorporate hydraulic and
      hydrological calculations into the design of urban areas. From data collection to
      final results, only freely available software and open platforms have been used:
      the U.S. EPA Storm Water Management Model (SWMM), QGis, PostgreSQL, PostGIS,
      SagaGIS, and GrassGIS. Each of these tools alone cannot provide all the necessary
      functionalities for large-scale projects, but once linked to GISWATER, a unique,
      fast, efficient, and accurate work methodology results. A case study of a newly
      urbanised area in the city of Gijon (northern Spain) has been utilised to apply
      this new methodology.

PMID- 30096914
TI  - Neuroprotective Properties of Asiatic Acid against 5-Fluorouracil Chemotherapy in
      the Hippocampus in an Adult Rat Model.
AB  - 5-fluorouracil or 5-FU (a chemotherapeutic medication) has been revealed to
      induce memory deficits in many cancer patients. Asiatic acid (AA) is a
      triterpenoid extract from Centella asiatica. This compound can ameliorate
      intracellular oxidative stress caused by chemotherapy drugs. Recent studies have
      shown that AA is capable of inhibiting neuronal generation and memory deficit
      produced by 5-FU chemotherapy. This study aimed to assess the molecular
      mechanisms of AA related to hippocampal neurogenesis and memory in rats receiving
      5-FU. Male Sprague Dawley rats were given AA (30 mg/kg) orally and given 5-FU (25
      mg/kg) by i.v. injection 5 times. Some rats were given AA for 20 days before and
      during 15-FU treatment (preventive), some received AA for 20 days after 5-FU
      treatment (recovery), and some underwent treatment with AA throughout the time of
      the experiment (throughout) for 40 days. Treatment with 5-FU caused significant
      reductions in Notch1, sex determining region Y-box 2 (SOX2), nestin, doublecortin
      (DCX), and nuclear factor erythroid 2-related factor 2 (Nrf2) levels within the
      hippocampus. In addition, 5-FU significantly increased p21 positive cell number
      in the subgranular zone (SGZ) and malondialdehyde (MDA) levels in the
      hippocampus. Administration with both AA and 5-FU in prevention and throughout
      was able to prevent decreases in Notch1 SOX2, nestin, DCX, and Nrf2 caused by 5
      FU. Treatment with AA also led to decreases in p21 positive cells and MDA levels
      in the hippocampus. These findings exhibit that AA has the ability to counteract
      the down-regulation of neurogenesis within the hippocampus and memory deficits
      caused by 5-FU via inhibiting oxidative stress and increasing neuroprotective
      properties.

PMID- 30096915
TI  - N6-Methyladenosine Role in Acute Myeloid Leukaemia.
AB  - We are currently assisting in the explosion of epitranscriptomics, which studies
      the functional role of chemical modifications into RNA molecules. Among more than
      100 RNA modifications, the N6-methyladenosine (m6A), in particular, has attracted
      the interest of researchers all around the world. m6A is the most abundant
      internal chemical modification in mRNA, and it can control any aspect of mRNA
      post-transcriptional regulation. m6A is installed by "writers", removed by
      "erasers", and recognized by "readers"; thus, it can be compared to the
      reversible and dynamic epigenetic modifications in histones and DNA. Given its
      fundamental role in determining the way mRNAs are expressed, it comes as no
      surprise that alterations to m6A modifications have a deep impact in cell
      differentiation, normal development and human diseases. Here, we review the
      proteins involved in m6A modification in mammals, m6A role in gene expression and
      its contribution to cancer development. In particular, we will focus on acute
      myeloid leukaemia (AML), which provides an initial indication of how alteration
      in m6A modification can disrupt normal cellular differentiation and lead to
      cancer.

PMID- 30096917
TI  - Research Progress Regarding Interfacial Characteristics and the Strengthening
      Mechanisms of Titanium Alloy/Hydroxyapatite Composites.
AB  - Titanium alloy/Hydroxyapatite (HA) composites have become a hot research topic in
      biomedical materials, while there are some challenges concerning bioactivity and
      mechanical properties such as low interface adhesion at the interface between
      metal and ceramic, complex interfacial reactions, and so on. Nevertheless,
      composites with reinforced phases can reach special properties that meet the
      requirements of biomedical materials due to the strong interfacial interactions
      between reinforcing phases (nano-carbon, partial oxides, and so on) and Titanium
      alloys or HA. This review summarizes the interface properties and mechanisms of
      Titanium alloy/HA composites, including interfacial bonding methods,
      strengthening and toughening mechanisms, and performance evaluation. On this
      basis, the interface characteristics and mechanisms of the Titaniumalloy/HA
      composites with enhanced phase are prospected. The results show that the
      interfacial bonding methods in the Titanium alloy/HA composites include chemical
      reactions and mechanical effects. The strengthening and toughening mechanisms
      contain grain refinement strengthening, second phase strengthening, solution
      strengthening, cracks and pulling out mechanisms, etc. This review provides a
      guidline for the fabrication of biocomposites with both mechanical properties and
      bioactivity.

PMID- 30096918
TI  - The Antifungal Properties of Epidermal Fatty Acid Esters: Insights from White
      Nose Syndrome (WNS) in Bats.
AB  - Numerous free fatty acids (FFAs) are known to have potent antifungal effects. The
      mammalian epidermis contains both FFAs and multiple classes of fatty acid esters,
      including 1-monoacylglycerols and wax esters. We thus hypothesized that wax
      esters and 1-monoacylglycerols composed of antifungal fatty acids would also have
      antifungal properties. We tested this hypothesis by examining the effects of 1
      monoacylglycerols, 1,3-diacylglycerols, and wax esters on the growth of
      Pseudogymnoascus destructans (Pd), the fungus that causes White-nose Syndrome
      (WNS) in North American bats by invading their epidermis. Laboratory experiments
      with Pd cultures demonstrated that: (a) three 1-monoacylglycerols (1
      monopalmitolein, 1-monoolein, and 1-monolinolein), as well as, (b) two wax
      esters, behenyl oleate and behenyl palmitoleate, profoundly inhibit Pd growth.
      The normal growth cycle of Pd was interrupted by addition of two cholesterol
      esters to the media as well. A bat species resistant to cutaneous Pd infections
      has these 1-monoacylglycerols in the epidermis, and another Pd resistant bat
      species has these wax esters in the sebum, thus cutaneous lipid composition is
      one factor which enables some bats to avoid WNS. Our experiments also revealed
      that the fatty acid esters which inhibit Pd growth are not hydrolyzed by the
      lipases secreted by this fungus, whereas the esters that do not inhibit Pd growth
      are hydrolyzed.

PMID- 30096919
TI  - Vitamin D Fortification of Fluid Milk Products and Their Contribution to Vitamin
      D Intake and Vitamin D Status in Observational Studies-A Review.
AB  - Fluid milk products are systematically, either mandatorily or voluntarily,
      fortified with vitamin D in some countries but their overall contribution to
      vitamin D intake and status worldwide is not fully understood. We searched the
      PubMed database to evaluate the contribution of vitamin D-fortified fluid milk
      products (regular milk and fermented products) to vitamin D intake and serum or
      plasma 25-hydroxyvitamin D (25(OH)D) status in observational studies during 1993
      2017. Twenty studies provided data on 25(OH)D status (n = 19,744), and 22
      provided data on vitamin D intake (n = 99,023). Studies showed positive
      associations between the consumption of vitamin D-fortified milk and 25(OH)D
      status in different population groups. In countries with a national vitamin D
      fortification policy covering various fluid milk products (Finland, Canada,
      United States), milk products contributed 28-63% to vitamin D intake, while in
      countries without a fortification policy, or when the fortification covered only
      some dairy products (Sweden, Norway), the contribution was much lower or
      negligible. To conclude, based on the reviewed observational studies, vitamin D
      fortified fluid milk products contribute to vitamin D intake and 25(OH)D status.
      However, their impact on vitamin D intake at the population level depends on
      whether vitamin D fortification is systematic and policy-based.

PMID- 30096920
TI  - Surface-Plasmon-Resonance-Based Optical Fiber Curvature Sensor with Temperature
      Compensation by Means of Dual Modulation Method.
AB  - Curvature measurement plays an important role in many fields. Aiming to overcome
      shortcomings of the existing optical fiber curvature sensors, such as complicated
      structure and difficulty in eliminating temperature noise, we proposed and
      demonstrated a simple optical fiber curvature sensor based on surface plasmon
      resonance. By etching cladding of the step-index multimode fiber and plating gold
      film on the bare core, the typical Kretschmann configuration is implemented on
      fiber, which is used as the bending-sensitive region. With increases in the
      curvature of the optical fiber, the resonance wavelength of the SPR (Surface
      Plasmon Resonance) dip linear red-shifts while the transmittance decreases
      linearly. In the curvature range between 0 and 9.17 m-1, the wavelength
      sensitivity reached 1.50 nm/m-1 and the intensity sensitivity reached -3.66%/m-1.
      In addition, with increases in the ambient temperature, the resonance wavelength
      of the SPR dips linearly blueshifts while the transmittance increases linearly.
      In the temperature range between 20 and 60  degrees C, the wavelength sensitivity
      is -0.255 nm/ degrees C and the intensity sensitivity is 0.099%/ degrees C. The
      sensing matrix is built up by combining the aforementioned four sensitivities. By
      means of the dual modulation method, the cross-interference caused by temperature
      change is eliminated. Additionally, simultaneous measurement of curvature and
      temperature is realized.

PMID- 30096924
TI  - Alkali Release from Aggregates in Long-Service Concrete Structures: Laboratory
      Test Evaluation and ASR Prediction.
AB  - This paper proposes a simple model for predicting the development of deleterious
      expansion from alkali-silica reaction (ASR) in long-service concrete structures.
      This model is based on some composition and reactivity parameters related to ASR,
      including the long-term alkali contribution by aggregates to concrete structures.
      This alkali contribution was estimated by means of a laboratory extraction test,
      appositely developed in this study in order to maximize the alkali extraction
      within relatively short testing times and with low leaching solution/aggregate
      ratios. The proposed test is a modification of the Italian Standard test method
      UNI 11417-2 (Ente Nazionale Italiano di Normazione) and it consists of subjecting
      an aggregate sample to leaching with saturated calcium hydroxide solution in a
      laboratory autoclave at 105  degrees C. Nine natural ASR-susceptible aggregates
      (seven sands and two coarse aggregates) were tested and the following optimized
      test conditions were found: leaching solution/aggregate weight ratio = 0.6; solid
      calcium hydroxide/aggregate weight ratio = 0.05; test duration = 120 h. The
      results of the optimized alkali extraction tests were used in the proposed model
      for predicting the potential development of long-term ASR expansion in concrete
      dams. ASR predictions congruent with both the field experience and the ASR
      prevention criteria recommended by European Committee for Standardization
      Technical Report CEN/TR 16349:2012 were found, thus indicating the suitability of
      the proposed model.

PMID- 30096923
TI  - Optical Properties of Silver-Mediated DNA from Molecular Dynamics and Time
      Dependent Density Functional Theory.
AB  - We report a combined quantum mechanics/molecular mechanics (QM/MM) molecular
      dynamics and time-dependent density functional (TDDFT) study of metal-mediated
      deoxyribonucleic acid (M-DNA) nanostructures. For the Ag + -mediated guanine
      tetramer, we found the maug-cc-pvdz basis set to be sufficient for calculating
      electronic circular dichroism (ECD) spectra. Our calculations further show that
      the B3LYP, CAM-B3LYP, B3LYP*, and PBE exchange-correlation functionals are all
      able to predict negative peaks in the measured ECD spectra within a 20 nm range.
      However, a spurious positive peak is present in the CAM-B3LYP ECD spectra. We
      trace the origins of this spurious peak and find that is likely due to the
      sensitivity of silver atoms to the amount of Hartree-Fock exchange in the
      exchange-correlation functional. Our presented approach provides guidance for
      future computational investigations of other Ag + -mediated DNA species.

PMID- 30096922
TI  - Intrinsic Iron Release Is Associated with Lower Mortality in Patients with Stable
      Coronary Artery Disease-First Report on the Prospective Relevance of Intrinsic
      Iron Release.
AB  - Intrinsic iron release is discussed to have favorable effects in coronary artery
      disease (CAD). The aim of this study was to evaluate the prognostic relevance of
      intrinsic iron release in patients with CAD. Intrinsic iron release was based on
      a definition including hepcidin and soluble transferrin receptor (sTfR). In a
      cohort of 811 patients with angiographically documented CAD levels of hepcidin
      and sTfR were measured at baseline. Systemic body iron release was defined as low
      levels of hepcidin (<24 ng/mL) and high levels of sTfR (>=2 mg/L). A commercially
      available ELISA (DRG) was used for measurements of serum hepcidin. Serum sTfR was
      determined by using an automated immunoassay (). Cardiovascular mortality was the
      main outcome measure. The criteria of intrinsic iron release were fulfilled in
      32.6% of all patients. Significantly lower cardiovascular mortality rates were
      observed in CAD patients with systemic iron release. After adjustment for body
      mass index, smoking status, hypertension, diabetes, dyslipidemia, sex, and age,
      the hazard ratio for future cardiovascular death was 0.41. After an additional
      adjustment for surrogates of the size of myocardial necrosis (troponin I), anemia
      (hemoglobin), and cardiac function and heart failure severity (N-terminal pro B
      type natriuretic peptide), this association did not change (Hazard ratio 0.37
      (95% confidence interval 0.14-0.99), p = 0.047). In conclusion, significantly
      lower cardiovascular mortality rates were observed in CAD patients with intrinsic
      iron release shown during follow-up.

PMID- 30096925
TI  - Self-Healing Property of Ultra-Thin Wearing Courses by Induction Heating.
AB  - Ultra-thin wearing course (UTWC) has been developed in pavement preventive
      maintenance for many years. However, how to prolong the service life of UTWC
      still requires further research. This study introduced AC-5 and SMA-5 asphalt
      mixtures, which can be induction heated. Steel fiber and steel slag were used in
      the mixtures as additives. Marshall Stability and induction heating property of
      mixtures were characterized. In addition, self-healing property of UTWC materials
      had been emphatically conducted. Adding steel fiber in mixtures led to higher
      Marshall Stability and lower flow value, while steel slag generally showed a
      negative effect. Induction heating property showed a positive relationship with
      the additives. Induction heating time was positively correlated to the healing
      ratio of the mixtures. Induction heating on the mixtures could recover the
      strength of mixtures to a certain degree. Mixtures with more steel fiber showed a
      higher healing ratio. Basalt-steel slag based mixtures showed better healing
      ratios than the basalt based mixtures. The healing ratios of mixtures illustrated
      a decreasing tendency as the healing cycle increased.

PMID- 30096921
TI  - Beneficial Effect of Intestinal Fermentation of Natural Polysaccharides.
AB  - With the rapid development of modern society, many chronic diseases are
      increasing including diabetes, obesity, cardiovascular diseases, etc., which
      further cause an increased death rate worldwide. A high caloric diet with reduced
      natural polysaccharides, typically indigestible polysaccharides, is considered a
      health risk factor. With solid evidence accumulating that indigestible
      polysaccharides can effectively prevent and/or ameliorate symptoms of many
      chronic diseases, we give a narrative review of many natural polysaccharides
      extracted from various food resources which mainly contribute their health
      beneficial functions via intestinal fermentation.

PMID- 30096926
TI  - Quantum Modeling: A Bridge between the Pumping and Signaling Functions of Na/K
      ATPase.
AB  - Although the signaling function of Na/K-ATPase has been studied for decades, the
      chasm between the pumping function and the signaling function of Na/K-ATPase is
      still an open issue. This article explores the relationship between ion pumping
      and signaling with attention to the amplification of oxidants through this
      signaling function. We specifically consider the Na/K-ATPase with respect to its
      signaling function as a superposition of different states described for its
      pumping function. We then examine how alterations in the relative amounts of
      these states could alter signaling through the Src-EGFR-ROS pathway. Using
      assumptions based on some experimental observations published by our laboratories
      and others, we develop some predictions regarding cellular oxidant stress.

PMID- 30096927
TI  - Energy-Aware Control of Data Compression and Sensing Rate for Wireless
      Rechargeable Sensor Networks.
AB  - Wireless rechargeable sensor nodes can collect additional data, which leads to an
      increase in the precision of data analysis, when enough harvested energy is
      acquired. However, because such nodes increase the amount of sensory data, some
      nodes (especially near the sink) may blackout because more transmitted data can
      make relaying nodes expend more energy. In this paper, we propose an energy-aware
      control scheme of data compression and sensing rate to maximize the amount of
      data collected at the sink, while minimizing the blackout time. In this scheme,
      each dominant node determines the data quota that all its descendant nodes can
      transmit during the next period, which operates with an efficient energy
      allocation scheme. Then, the node receiving the quota selects an appropriate data
      compression algorithm and sensing rate according to both its quota and allocated
      energy during the next period, so as not to exhaust the energy of nodes near the
      sink. Experimental results verify that the proposed scheme collects more data
      than other schemes, while suppressing the blackout of nodes. We also found that
      it adapts better to changes in node density and harvesting environments.

PMID- 30096928
TI  - Design, Fabrication and Testing of a High-Sensitive Fibre Sensor for Tip
      Clearance Measurements.
AB  - A highly sensitive fibre bundle-based reflective optical sensor has been designed
      and fabricated for Tip Clearance measurements in a turbine rig. The sensor offers
      high spatial and temporal resolution. The sensor probe consists of a single-mode
      transmitting fibre and two concentric rings of receiving multimode fibres that
      collect reflected light in a differential detection gain configuration, yielding
      a highly linear calibration curve for distance measurements. The clearance
      measurement range is approximately 2 mm around the central point fixed at 3.2 mm
      from the probe tip, and the sensitivity of the probe is 61.73 mm-1. The fibre
      bundle has been designed to ensure that the distance security specifications
      required for the experimental program of the turbine are met. The optical sensor
      has operated under demanding conditions set by the blade and casing design. The
      experimental results obtained so far are promising and lead us to think that the
      optical sensor has great potential for online clearance measurements with high
      precision.

PMID- 30096930
TI  - Performance Analysis of Latency-Aware Data Management in Industrial IoT Networks.
AB  - Maintaining critical data access latency requirements is an important challenge
      of Industry 4.0. The traditional, centralized industrial networks, which transfer
      the data to a central network controller prior to delivery, might be incapable of
      meeting such strict requirements. In this paper, we exploit distributed data
      management to overcome this issue. Given a set of data, the set of consumer nodes
      and the maximum access latency that consumers can tolerate, we consider a method
      for identifying and selecting a limited set of proxies in the network where data
      needed by the consumer nodes can be cached. The method targets at balancing two
      requirements; data access latency within the given constraints and low numbers of
      selected proxies. We implement the method and evaluate its performance using a
      network of WSN430 IEEE 802.15.4-enabled open nodes. Additionally, we validate a
      simulation model and use it for performance evaluation in larger scales and more
      general topologies. We demonstrate that the proposed method (i) guarantees
      average access latency below the given threshold and (ii) outperforms traditional
      centralized and even distributed approaches.

PMID- 30096931
TI  - Decentralized Online Simultaneous Localization and Mapping for Multi-Agent
      Systems.
AB  - Planning tasks performed by a robotic agent require previous access to a map of
      the environment and the position where the agent is located. This creates a
      problem when the agent is placed in a new environment. To solve it, the RA must
      execute the task known as Simultaneous Location and Mapping (SLAM) which locates
      the agent in the new environment while generating the map at the same time,
      geometrically or topologically. One of the big problems in SLAM is the amount of
      memory required for the RA to store the details of the environment map. In
      addition, environment data capture needs a robust processing unit to handle data
      representation, which in turn is reflected in a bigger RA unit with higher energy
      use and production costs. This article presents a design for a system capable of
      a decentralized implementation of SLAM that is based on the use of a system
      comprised of wireless agents capable of storing and distributing the map as it is
      being generated by the RA. The proposed system was validated in an environment
      with a surface area of 25 m 2 , in which it was capable of generating the
      topological map online, and without relying on external units connected to the
      system.

PMID- 30096929
TI  - Exposure to Environmental and Occupational Particulate Air Pollution as a
      Potential Contributor to Neurodegeneration and Diabetes: A Systematic Review of
      Epidemiological Research.
AB  - It has been hypothesised that environmental air pollution, especially airborne
      particles, is a risk factor for type 2 diabetes mellitus (T2DM) and
      neurodegenerative conditions. However, epidemiological evidence is inconsistent
      and has not been previously evaluated as part of a systematic review. Our
      objectives were to carry out a systematic review of the epidemiological evidence
      on the association between long-term exposure to ambient air pollution and T2DM
      and neurodegenerative diseases in adults and to identify if workplace exposures
      to particles are associated with an increased risk of T2DM and neurodegenerative
      diseases. Assessment of the quality of the evidence was carried out using the
      GRADE system, which considers the quality of the studies, consistency,
      directness, effect size, and publication bias. Available evidence indicates a
      consistent positive association between ambient air pollution and both T2DM and
      neurodegeneration risk, such as dementia and a general decline in cognition.
      However, corresponding evidence for workplace exposures are lacking. Further
      research is required to identify the link and mechanisms associated with
      particulate exposure and disease pathogenesis and to investigate the risks in
      occupational populations. Additional steps are needed to reduce air pollution
      levels and possibly also in the workplace environment to decrease the incidence
      of T2DM and cognitive decline.

PMID- 30096932
TI  - Effects of Horticultural Therapy on Asian Older Adults: A Randomized Controlled
      Trial.
AB  - : The effect of horticultural therapy (HT) on immune and endocrine biomarkers
      remains largely unknown. We designed a waitlist-control randomized controlled
      trial to investigate the effectiveness of HT in improving mental well-being and
      modulating biomarker levels. A total of 59 older adults was recruited, with 29
      randomly assigned to the HT intervention and 30 to the waitlist control group.
      The participants attended weekly intervention sessions for the first 3 months and
      monthly sessions for the subsequent 3 months. Biological and psychosocial data
      were collected. Biomarkers included IL-1beta, IL-6, sgp-130, CXCL12/SDF-1alpha,
      CCL-5/RANTES, BDNF (brain-derived neurotrophic factor), hs-CRP, cortisol and DHEA
      (dehydroepiandrosterone). Psychosocial measures examined cognitive functions,
      depression, anxiety, psychological well-being, social connectedness and
      satisfaction with life. A significant reduction in plasma IL-6 level (p = 0.02)
      was observed in the HT intervention group. For the waitlist control group,
      significant reductions in plasma CXCL12 (SDF-1alpha) (p = 0.003), CXCL5 (RANTES)
      (p = 0.05) and BDNF (p = 0.003) were observed. A significant improvement in
      social connectedness was also observed in the HT group (p = 0.01). CONCLUSION:
      HT, in reducing plasma IL-6, may prevent inflammatory disorders and through
      maintaining plasma CXCL12 (SDF-1alpha), may maintain hematopoietic support to the
      brain. HT may be applied in communal gardening to enhance the well-being of older
      adults.

PMID- 30096933
TI  - Impedance Pumping and Resonance in a Multi-Vessel System.
AB  - Impedance pumping is a mechanism that generates flow in a compliant vessel by
      repeatedly actuating the vessel asymmetrically, without employing any internal
      valves, blades, or other mechanisms. The net flow is obtained by establishing a
      constructive wave pattern. Elaborate studies of impedance pumping in a single
      vessel have shown that the flow rate strongly depends on the actuation frequency,
      as well as on other parameters, such as actuator location and amplitude, and that
      it operates best in the resonance mode. The present study extends these
      principles to a network of multiple compliant vessels, representing a
      cardiovascular system. The flow is modeled numerically by the one-dimensional
      approximation of the Navier-Stokes equations. Two configurations were examined,
      systems consisting of three and five compliant vessels. First, the natural
      frequencies of these configurations were identified. Then, the dependence of the
      net flow rate (NFR) on the actuating frequency was explored, showing that
      impedance pumping operates best in the resonance mode in the case of a network of
      vessels as well. The impact of other parameters were studied as well, such as the
      location of one or two actuators, actuation amplitude, actuator width, the duty
      cycle, and the phase lag between the actuators. The results show that impedance
      pumps can generate significant NFR and the obtained NFR can be manipulated by
      properly setting up one or more of the governing parameters. These findings
      indicate that impedance pumping principles may be applied to flow control of the
      cardiovascular system.

PMID- 30096934
TI  - Epithelial-Mesenchymal Transition with Malignant Transformation Leading Multiple
      Metastasis from Disseminated Peritoneal Leiomyomatosis.
AB  - Disseminated peritoneal leiomyomatosis (DPL) is a rare condition that is
      characterized by the presence of multiple subperitoneal or peritoneal smooth
      muscle nodules of varying sizes on the omentum and peritoneal surfaces, grossly
      mimicking disseminated carcinoma. DPL usually develops in premenopausal women
      with a benign course, and it is often found incidentally during abdominal
      surgery. Malignant transformation is a rare clinical course of DPL. Only a few
      studies have focused on DPL transformation into a leiomyosarcoma. Herein, we
      describe the case of a 61-year-old woman with a history of recurrent leiomyoma of
      the uterus who presented with intermittent progressive abdominal pain. The
      imaging study revealed a huge heterogeneous density mass in the pelvic region
      with pulmonary and hepatic metastases. Exploratory laparotomy and debulking
      surgery were performed, and showed the coexistence of DPL and leiomyosarcoma. She
      died approximately one month after the diagnosis because of rapid progression of
      pleural effusion due to malignancy. This case highlights the clinical features of
      DPL and its malignant transformation and metastasis so physicians can make an
      early diagnosis and provide timely management.

PMID- 30096935
TI  - Basic Medium Heterogeneous Solution Synthesis of alpha-MnO2 Nanoflakes as an
      Anode or Cathode in Half Cell Configuration (vs. Lithium) of Li-Ion Batteries.
AB  - Nano alpha-MnO2 is usually synthesized under hydrothermal conditions in acidic
      medium, which results in materials easily undergoing thermal reduction and offers
      single crystals often over 100 nm in size. In this study, alpha-MnO2 built up of
      inter-grown ultra-small nanoflakes with 10 nm thickness was produced in a rapid
      two-step procedure starting via partial reduction in solution in basic medium
      subsequently followed by co-proportionation in thermal treatment. This approach
      offers phase-pure alpha-MnO2 doped with potassium (cryptomelane type K0.25Mn8O16
      structure) demonstrating considerable chemical and thermal stability. The
      reaction pathways leading to this new morphology and structure have been
      discussed. The MnO2 electrodes produced from obtained nanostructures were tested
      as electrodes of lithium ion batteries delivering initial discharge capacities of
      968 mAh g-1 for anode (0 to 2.0 V) and 317 mAh g-1 for cathode (1.5 to 3.5 V) at
      20 mA g-1 current density. At constant current of 100 mA g-1, stable cycling of
      anode achieving 660 mAh g-1 and 145 mAh g-1 for cathode after 200 cycles is
      recorded. Post diagnostic analysis of cycled electrodes confirmed the electrode
      materials stability and structural properties.

PMID- 30096936
TI  - Precipitation Characteristics of the Metastable gamma" Phase in a Cu-Ni-Be Alloy.
AB  - The precipitation sequence of a Cu-Ni-Be alloy is: alpha-Cu supersaturated solid
      solution -> Guinier-Preston (G.P.) zones -> metastable gamma" -> gamma' -> stable
      gamma (NiBe) phase. The micro-hardness and electrical conductivity during the
      aging process were measured. The precipitation characteristics and the
      distribution of the gamma" phase, under peak aging conditions, were analyzed by X
      ray diffraction (XRD), transmission electron microscopy (TEM), selected area
      diffraction pattern (SADP), and high-resolution transmission electron microscopy
      (HRTEM). The results show that the orientation relationship of the gamma''
      phase/alpha-Cu matrix is: (001)p//(001)alpha; [100]p//[110]alpha (p:
      Precipitates, alpha: alpha-Cu supersaturated solid solution), which is in
      accordance with the Bain relationship in a FCC/BCC (face centered cubic/body
      centered cubic) structure, with the unique habit plane being {001}alpha. While
      the zone axis is parallel to [001]alpha, three forms of gamma" phases are
      distributed on the projection surface at the same time. The (001) reciprocal
      lattice positions of gamma'' phase in SADP are diffusely scattered, which is
      consistent with the variation of the d(001) value of the gamma'' phase. The intra
      range variation is related to the distortion of the (001) plane of the gamma"
      phase, due to interfacial dislocations and distortion strain fields. The lattice
      of the gamma" phase in the HRTEM images was measured as a = b = 0.259 +/- 0.002
      nm and c = 0.27-0.32 nm. With the increase of thermal exposure time, the stable
      gamma phase has a NiBe phase structure (Standard Card Number: PDF#03-1098, a = b
      = c = 0.261 nm), and the long diffuse scattering spots will transform into single
      bright spots. The edge dislocation, generated by interfacial mismatch, promotes
      the formation of an optimal structure of the precipitated phase, which is the
      priority of growth in the direction of [110]p.

PMID- 30096938
TI  - Automated Calibration Method for Eye-Tracked Autostereoscopic Display.
AB  - In this paper, we propose an automated calibration system for an eye-tracked
      autostereoscopic display (ETAD). Instead of calibrating each device sequentially
      and individually, our method calibrates all parameters of the devices at the same
      time in a fixed environment. To achieve this, we first identify and classify all
      parameters by establishing a physical model of the ETAD and describe a rendering
      method based on a viewer's eye position. Then, we propose a calibration method
      that estimates all parameters at the same time using two images. To automate the
      proposed method, we use a calibration module of our own design. Consequently, the
      calibration process is performed by analyzing two images captured by onboard
      camera of the ETAD and the external camera of the calibration module. For
      validation, we conducted two types of experiments, one with simulation for
      quantitative evaluation, and the other with a real prototype ETAD device for
      qualitative assessment. Experimental results demonstrate the crosstalk of the
      ETAD was improved to 8.32%. The visual quality was also improved to 30.44% in the
      peak-signal-to-noise ratio (PSNR) and 40.14% in the structural similarity (SSIM)
      indexes when the proposed calibration method is applied. The whole calibration
      process was carried out within 1.5 s without any external manipulation.

PMID- 30096937
TI  - Current and Emerging Techniques for High-Pressure Membrane Integrity Testing.
AB  - Ideally, pressure driven membrane processes used in wastewater treatment such as
      reverse osmosis and nanofiltration should provide a complete physical barrier to
      the passage of pathogens such as enteric viruses. In reality, manufacturing
      imperfections combined with membrane ageing and damage can result in breaches as
      small as 20 to 30 nm in diameter, sufficient to allow enteric viruses to
      contaminate the treated water and compromise public health. In addition to
      continuous monitoring, frequent demonstration of the integrity of membranes is
      required to provide assurance that the barrier to the passage of such
      contaminants is intact. Existing membrane integrity monitoring systems, however,
      are limited and health regulators typically credit high-pressure membrane systems
      with only 2 log10 virus rejection, well below their capability. A reliable real
      time method that can recognize the true rejection potential of membrane systems
      greater than 4 log10 has not yet been established. This review provides a
      critical evaluation of the current methods of integrity monitoring and identifies
      novel approaches that have the potential to provide accurate, representative
      virus removal efficiency estimates.

PMID- 30096940
TI  - Emission Characteristics of Particulate Matter, Volatile Organic Compounds, and
      Trace Elements from the Combustion of Coals in Mongolia.
AB  - This study characterized emissions of particulate matter (PM), volatile organic
      compounds (VOCs), heavy metals, and anions from Mongolian bituminous coals in a
      controlled heating experiment. Three coal samples from Alag Tolgoi (coal 1),
      Baganuur (coal 2), and Nalaikh (coal 3) were combusted at a constant heat flux of
      50 kW/m2 using a dual-cone calorimeter. The coal samples were commonly used in
      ger district of Ulaanbaatar, Mongolia. PM10 emission factors were 1122.9 +/-
      526.2, 958.1 +/- 584.0, and 472.0 +/- 57.1 mg/kg for coal samples 1, 2, and 3,
      respectively. PM with a diameter of 0.35-0.45 um was dominant and accounted for
      41, 34, and 48% of the total PM for coal samples 1, 2, and 3, respectively. The
      emissions of PM and VOC from coals commonly used in Ulaanbaatar, Mongolia were
      significant enough to cause extremely high levels of indoor and outdoor air
      pollution.

PMID- 30096941
TI  - Humidity Measurement in Carbon Dioxide with Capacitive Humidity Sensors at Low
      Temperature and Pressure.
AB  - In experimental chambers for simulating the atmospheric near-surface conditions
      of Mars, or in situ measurements on Mars, the measurement of the humidity in
      carbon dioxide gas at low temperature and under low pressure is needed. For this
      purpose, polymer-based capacitive humidity sensors are used; however, these
      sensors are designed for measuring the humidity in the air on the Earth. The
      manufacturers provide only the generic calibration equation for standard
      environmental conditions in air, and temperature corrections of humidity signal.
      Because of the lack of freely available information regarding the behavior of the
      sensors in CO2, the range of reliable results is limited. For these reasons,
      capacitive humidity sensors (Sensirion SHT75) were tested at the German Aerospace
      Center (DLR) in its Martian Simulation Facility (MSF). The sensors were
      investigated in cells with a continuously humidified carbon dioxide flow, for
      temperatures between -70  degrees C and 10  degrees C, and pressures between 10
      hPa and 1000 hPa. For 28 temperature-pressure combinations, the sensor
      calibration equations were calculated together with temperature-dependent
      formulas for the coefficients of the equations. The characteristic curves
      obtained from the tests in CO2 and in air were compared for selected temperature
      pressure combinations. The results document a strong cross-sensitivity of the
      sensors to CO2 and, compared with air, a strong pressure sensitivity as well. The
      reason could be an interaction of the molecules of CO2 with the adsorption sites
      on the thin polymeric sensing layer. In these circumstances, an individual
      calibration for each pressure with respect to temperature is required. The
      performed experiments have shown that this kind of sensor can be a suitable,
      lightweight, and relatively inexpensive choice for applications in harsh
      environments such as on Mars.

PMID- 30096939
TI  - Application of Electronic-Nose Technologies and VOC-Biomarkers for the
      Noninvasive Early Diagnosis of Gastrointestinal Diseases ?.
AB  - Conventional methods utilized for clinical diagnosis of gastrointestinal (GI)
      diseases have employed invasive medical procedures that cause stress, anxiety and
      pain to patients. These methods are often expensive, time-consuming, and require
      sophisticated chemical-analysis instruments and advanced modeling procedures to
      achieve diagnostic interpretations. This paper reviews recent applications of
      simpler, electronic-nose (e-nose) devices for the noninvasive early diagnosis of
      a wide range of GI diseases by collective analysis of headspace volatile organic
      compound (VOC)-metabolites from clinical samples to produce disease-specific
      aroma signatures (VOC profiles). A different "metabolomics" approach to GI
      disease diagnostics, involving identifications and quantifications of disease VOC
      metabolites, are compared to the electronic-nose approach based on diagnostic
      costs, accuracy, advantages and disadvantages. The importance of changes in gut
      microbiome composition that result from disease are discussed relative to effects
      on disease detection. A new diagnostic approach, which combines the use of e-nose
      instruments for early rapid prophylactic disease-screenings with targeted
      identification of known disease biomarkers, is proposed to yield cheaper, quicker
      and more dependable diagnostic results. Some priority future research needs and
      coordination for bringing e-nose instruments into routine clinical practice are
      summarized.

PMID- 30096942
TI  - Road Traffic Noise, Air Pollutants, and the Prevalence of Cardiovascular Disease
      in Taichung, Taiwan.
AB  - Background: A few studies have investigated the interaction between exposure to
      road traffic noise, air pollutants, and cardiovascular disease (CVD), but their
      results were inconsistent. This cross-sectional study investigated whether road
      traffic noise, particulate matter with dynamic diameter less than 10 MUm (PM10)
      and nitrogen dioxides (NO2) exposure were independently associated with the risk
      of CVD. Methods: We recruited 663 volunteers who had been living near main roads
      for more than three years in 2008. Information concerning the subjects' home
      addresses was combined with noise measurements at 42 locations and annual average
      of air pollutants from 2 monitoring stations to estimate individual exposure.
      Multivariate logistic regression was used to calculate the odds ratio (OR) for
      diagnosed CVD, adjusting for potential confounders and co-exposure. Results: Only
      per 5-dBA increase in road traffic noise was significantly associated with
      elevated risk of CVD (adjusted OR = 2.23, 95% confidence interval (CI) = 1.26
      3.93) in the single-exposure models. Such association was aggravated (adjusted OR
      = 2.96, 95% CI = 1.41-6.23) after adjustment for total traffic and PM10 or NO2 in
      the two-exposure models. Conclusions: Road traffic noise exposure may be
      associated with the increasing prevalence of CVD. No synergistic association was
      observed between co-exposure to noise and air pollutants and the risk of CVD.

PMID- 30096944
TI  - A Fusion Method for Combining Low-Cost IMU/Magnetometer Outputs for Use in
      Applications on Mobile Devices.
AB  - This paper presents a fusion method for combining outputs acquired by low-cost
      inertial measurement units and electronic magnetic compasses. Specifically,
      measurements of inertial accelerometer and gyroscope sensors are combined with no
      inertial magnetometer sensor measurements to provide the optimal three
      dimensional (3D) orientation of the sensors' axis systems in real time. The
      method combines Euler-Cardan angles and rotation matrix for attitude and heading
      representation estimation and deals with the "gimbal lock" problem. The
      mathematical formulation of the method is based on Kalman filter and takes into
      account the computational cost required for operation on mobile devices as well
      as the characteristics of the low-cost microelectromechanical sensors. The method
      was implemented, debugged, and evaluated in a desktop software utility by using a
      low-cost sensor system, and it was tested in an augmented reality application on
      an Android mobile device, while its efficiency was evaluated experimentally.

PMID- 30096945
TI  - Ultrasound Sensors for Diaphragm Motion Tracking: An Application in Non-Invasive
      Respiratory Monitoring.
AB  - This paper introduces a novel respiratory detection system based on diaphragm
      wall motion tracking using an embedded ultrasound sensory system. We assess the
      utility and accuracy of this method in evaluating the function of the diaphragm
      and its contribution to respiratory workload. The developed system is able to
      monitor the diaphragm wall activity when the sensor is placed in the zone of
      apposition (ZOA). This system allows for direct measurements with only one
      ultrasound PZT5 piezo transducer. The system generates pulsed ultrasound waves at
      2.2 MHz and amplifies reflected echoes. An added benefit of this system is that
      due to its design, the respiratory signal is less subject to motion artefacts.
      Promising results were obtained from six subjects performing six tests per
      subject with an average respiration detection sensitivity and specificity of 84%
      and 93%, respectively. Measurements were compared to a gold standard commercial
      spirometer. In this study, we also compared our measurements to other
      conventional methods such as inertial and photoplethysmography (PPG) sensors.

PMID- 30096943
TI  - Speciation Theory of Carcinogenesis Explains Karyotypic Individuality and Long
      Latencies of Cancers.
AB  - It has been known for over 100 years that cancers have individual karyotypes and
      arise only years to decades after initiating carcinogens. However, there is still
      no coherent theory to explain these definitive characteristics of cancer. The
      prevailing mutation theory holds that cancers are late because the primary cell
      must accumulate 3-8 causative mutations to become carcinogenic and that
      mutations, which induce chromosomal instability (CIN), generate the individual
      karyotypes of cancers. However, since there is still no proven set of mutations
      that transforms a normal to a cancer cell, we have recently advanced the theory
      that carcinogenesis is a form of speciation. This theory predicts carcinogens
      initiate cancer by inducing aneuploidy, which automatically unbalances thousands
      of genes and thus catalyzes chain-reactions of progressive aneuploidizations.
      Over time, these aneuploidizations have two endpoints, either non-viable
      karyotypes or very rarely karyotypes of new autonomous and immortal cancers.
      Cancer karyotypes are immortalized despite destabilizing congenital aneuploidy by
      clonal selections for autonomy-similar to those of conventional species. This
      theory predicts that the very low probability of converting the karyotype of a
      normal cell to that of a new autonomous cancer species by random
      aneuploidizations is the reason for the karyotypic individuality of new cancers
      and for the long latencies from carcinogens to cancers. In testing this theory,
      we observed: (1) Addition of mutagenic and non-mutagenic carcinogens to normal
      human and rat cells generated progressive aneuploidizations months before
      neoplastic transformation. (2) Sub-cloning of a neoplastic rat clone revealed
      heritable individual karyotypes, rather than the non-heritable karyotypes
      predicted by the CIN theory. (3) Analyses of neoplastic and preneoplastic
      karyotypes unexpectedly identified karyotypes with sets of 3-11 new marker
      chromosomes without detectable intermediates, consistent with single-step
      origins. We conclude that the speciation theory explains logically the long
      latencies from carcinogen exposure and the individuality of cancers. In addition,
      the theory supports the single-step origins of cancers, because karyotypic
      autonomy is all-or-nothing. Accordingly, we propose that preneoplastic aneuploidy
      and clonal neoplastic karyotypes provide more reliable therapeutic indications
      than current analyses of thousands of mutations.

PMID- 30096947
TI  - Dynamic Tomographic Reconstruction of Deforming Volumes.
AB  - The motion of a sample while being scanned in a tomograph prevents its proper
      volume reconstruction. In the present study, a procedure is proposed that aims at
      estimating both the kinematics of the sample and its standard 3D imaging from a
      standard acquisition protocol (no more projection than for a rigid specimen). The
      proposed procedure is a staggered two-step algorithm where the volume is first
      reconstructed using a "Dynamic Reconstruction" technique, a variant of Algebraic
      Reconstruction Technique (ART) compensating for a "frozen" determination of the
      motion, followed by a Projection-based Digital Volume Correlation (P-DVC)
      algorithm that estimates the space/time displacement field, with a "frozen"
      microstructure and shape of the sample. Additionally, this procedure is combined
      with a multi-scale approach that is essential for a proper separation between
      motion and microstructure. A proof-of-concept of the validity and performance of
      this approach is proposed based on two virtual examples. The studied cases
      involve a small number of projections, large strains, up to 25%, and noise.

PMID- 30096946
TI  - Breakfast Consumption in French Children, Adolescents, and Adults: A Nationally
      Representative Cross-Sectional Survey Examined in the Context of the
      International Breakfast Research Initiative.
AB  - This study examines the consumption of breakfast on the basis of a 7-day dietary
      record (Comportements et Consommations Alimentaires en France 2012-2013) in a
      representative sample of French children (n = 426), adolescents (n = 250), and
      adults (n = 1045). A large majority of the participants were regular consumers of
      breakfast (5-7 times per week). Breakfast accounted for 17.6% of total daily
      energy (339.4 kcal). Breakfast was rich in carbohydrates (24% of total daily
      intake) and simple sugars (31% of total daily intake). Relative to its
      contribution in daily energy intake, breakfast contributed higher proportions in
      the daily intake of many vitamins (B, C), and minerals (calcium, iron, iodine,
      manganese, phosphorus, potassium, magnesium). The main foods/beverages
      contributing to breakfast changed with age, with increasing contributions of non
      wholegrain "bread and toasts" and "fruits", and a decreasing contribution of
      milk. Better quality of the diet, as measured by tertiles of the Nutrient Rich
      Food Index 9.3, was associated with higher intakes of cereal products (bread and
      breakfast cereals, particularly wholegrain), dairy (milk, fresh dairy), and fruit
      at breakfast. In conclusion, breakfast is regularly consumed in France and
      contributes significantly to diet quality but could be improved in terms of
      content in fiber and protein.

PMID- 30096948
TI  - Disentangling the Neural Basis of Cognitive Behavioral Therapy in Psychiatric
      Disorders: A Focus on Depression.
AB  - Background: Major depressive disorder (MDD) stands among the most frequent
      psychiatric disorders. Cognitive behavioral therapy (CBT) has been shown to be
      effective for treating depression, yet its neural mechanisms of action are not
      well elucidated. The objective of this work is to assess the available
      neuroimaging studies exploring CBT's effects in adult patients with MDD. Methods:
      Computerized databases were consulted till April 2018 and a research was
      conducted according to PRISMA guidelines in order to identify original research
      articles published at any time in English and French languages on this topic.
      Results: Seventeen studies were identified. Only one study was randomized
      comparing CBT to pharmacological interventions, and none included an effective
      control. Following CBT, changes occurred in cerebral areas that are part of the
      fronto-limbic system, namely the cingulate cortex, prefrontal cortex and amygdala
      hippocampal complex. However, the pattern of activation and connectivity in these
      areas varied across the studies. Conclusion: A considerable heterogeneity exists
      with regard to study design, adapted CBT type and intensity, and employed
      neuroimaging paradigms, all of which may partly explain the difference in
      studies' outcomes. The lack of randomization and effective controls in most of
      them makes it difficult to draw formal conclusion whether the observed effects
      are CBT mediated or due to spontaneous recovery. Despite the observed
      inconsistencies and dearth of data, CBT appears to exert its anti-depressant
      effects mainly by modulating the function of affective and cognitive networks
      devoted to emotions generation and control, respectively. This concept remains to
      be validated in large scale randomized controlled trials.

PMID- 30096950
TI  - Combined Calorimetry, Thermo-Mechanical Analysis and Tensile Test on Welded EN AW
      6082 Joints.
AB  - Wide softening zones are typical for welded joints of age hardened aluminium
      alloys. In this study, the microstructure evolution and distribution of
      mechanical properties resulting from welding processes of the aluminium alloy EN
      AW-6082 (AlSi1MgMn) was analysed by both in-situ and ex-situ investigations. The
      in-situ thermal analyses (TMA) included differential scanning calorimetry (DSC),
      which was used to characterise the dissolution and precipitation behaviour in the
      heat affected zone (HAZ) of welded joints. Thermo-mechanical analysis by means of
      compression tests was used to determine the mechanical properties of various
      states of the microstructure after the welding heat input. The necessary
      temperature-time courses in the HAZ for these methods were measured using
      thermocouples during welding. Additionally, ex-situ tensile tests were done both
      on specimens from the fusion zone and on welded joints, and their in-depth
      analysis with digital image correlation (DIC) accompanied by finite element
      simulations serve for the description of flow curves in different areas of the
      weld. The combination of these methods and the discussion of their results make
      an essential contribution to understand the influence of welding heat on the
      material properties, particularly on the softening behaviour. Furthermore, the
      distributed strength characteristic of the welded connections is required for an
      applicable estimation of the load-bearing capacity of welded aluminium structures
      by numerical methods.

PMID- 30096949
TI  - Modeling Endometrial Cancer: Past, Present, and Future.
AB  - Endometrial cancer is the most common type of cancer of the female reproductive
      tract. Although prognosis is generally good for patients with low-grade and early
      stage diseases, the outcomes for high-grade and metastatic/recurrent cases remain
      poor, since traditional chemotherapy regimens based on platinum and taxanes have
      limited effects. No targeted agents have been approved so far, although several
      new drugs have been tested without striking results in clinical trials. Over the
      last decades, many efforts have been made towards the establishment and
      development of preclinical models, aiming at recapitulating the structural and
      molecular determinants of the disease. Here, we present an overview of the most
      commonly used in vitro and in vivo models and discuss their peculiar features,
      describing their main applications and the value in the advancement of both
      fundamental and translational endometrial cancer research.

PMID- 30096952
TI  - Effect of Heat-Killed Lactobacillus paracasei KW3110 Ingestion on Ocular
      Disorders Caused by Visual Display Terminal (VDT) Loads: A Randomized, Double
      Blind, Placebo-Controlled Parallel-Group Study.
AB  - BACKGROUND: Visual display terminals (VDTs) emitting blue light can cause ocular
      disorders including eye fatigue. Some dietary constituents have been reported to
      be effective in improving ocular disorders while few clinical studies have been
      performed. We evaluated the effects of heat-killed Lactobacillus paracasei KW
      3110 on improving ocular disorders and symptoms of eye fatigue among healthy
      human subjects with VDT loads. METHODS: In vitro, the effect of L. paracasei
      KW3110 on blue light-induced human retinal pigment epithelial (ARPE-19) cell
      damage. For clinical studies, 62 healthy Japanese volunteers of 35 to 45 years of
      age who had experienced eye fatigue were randomized into two groups and given a
      placebo or L. paracasei KW3110-containing supplements for eight weeks. The
      primary endpoint was changes in VDT load-induced eye fatigue as determined by
      critical flicker frequency four and eight weeks after the start of
      supplementation. RESULTS: In vitro, blue light-induced human retinal cell death
      was suppressed with the culture supernatants of cells treated with L. paracasei
      KW3110. In clinical study, the VDT load-induced reduction of critical flicker
      frequency tended to be milder in the L. paracasei KW3110 group when compared with
      the placebo group during the fourth week. Subgroup analysis classified by the
      degree of eye fatigue showed that the VDT load-induced reduction of critical
      flicker frequency was significantly better in the high-level eye fatigue subjects
      from the L. paracasei KW3110 group when compared with the placebo group during
      the fourth week (p = 0.020). CONCLUSIONS: L. paracasei KW3110 suppressed blue
      light-induced retinal pigment epithelial cell death. In the clinical study,
      ingestion of L. paracasei KW3110 had a potential to improve eye fatigue induced
      by VDT loads especially high levels of eye fatigue. However, further studies
      should be required to show more dependable clinical efficacy of L. paracasei
      KW3110.

PMID- 30096951
TI  - Adipocytokine Regulation and Antiangiogenic Activity Underlie the Molecular
      Mechanisms of Therapeutic Effects of Phyllanthus niruri against Non-Alcoholic
      Fatty Liver Disease.
AB  - The growth of adipose tissues is considered angiogenesis-dependent during non
      alcoholic fatty liver disease (NAFLD). We have recently reported that our
      standardized 50% methanolic extract (ME) of Phyllanthus niruri (50% ME of P.
      niruri) has alleviated NAFLD in Sprague-Dawley rats. This study aimed to assess
      the molecular mechanisms of action, and to further evaluate the antiangiogenic
      effect of this extract. NAFLD was induced by eight weeks of high-fat diet, and
      treatment was applied for four weeks. Antiangiogenic activity was assessed by
      aortic ring assay and by in vitro tests. Our findings demonstrated that the
      therapeutic effects of 50% ME among NAFLD rats, were associated with a
      significant increase in serum adiponectin, reduction in the serum levels of RBP4,
      vaspin, progranulin, TNF-alpha, IL-6, and significant downregulation of the
      hepatic gene expression of PPARgamma, SLC10A2, and Collalpha1. Concomitantly, 50%
      ME of P. niruri has exhibited a potent antiangiogenic activity on ring assay,
      cell migration, vascular endothelial growth factor (VEGF), and tube formation,
      without any cytotoxic effect. Together, our findings revealed that the protective
      effects of P. niruri against NAFLD might be attributed to its antiangiogenic
      effect, as well as to the regulation of adipocytokines and reducing the
      expression of adipogenic genes.

PMID- 30096954
TI  - Reliability and Use of Copenhagen Burnout Inventory in Italian Sample of
      University Professors.
AB  - Academics often have to face with burnout syndrome at work. This cross-sectional
      study evaluates the reliability of the Italian version of the Copenhagen Burnout
      Inventory (CBI) in a sample of Academics of Sapienza University of Faculty of
      Medicine and Pharmacy, through an online questionnaire composed of the CBI, SF12
      Health Survey, and Positivity Scale. Univariate, bivariate, multivariate
      analyses, and Cronbach alpha coefficients of CBI were performed. Ninety-five
      participants completed the questionnaire (response rate 85%). Cronbach's alpha of
      the three domains were high (0.892, 0.868, and 0.836). Women, younger and part
      time professors reported higher score in personal (p = 0.025; 0.060) and work
      burnout. In multivariate analysis decreasing age (beta = -0.263; p = 0.001);
      being a professor in environmental technicians (beta = -0.120; p = 0.098); and
      low mental (beta = -0.263; p = 0.020), physical (beta = -0.319; p <= 0.001) and
      positivity scores (beta = -0.237; p = 0.031) predict significantly higher
      personal burnout. Low physical (beta = -0.346; p < 0.001) and mental (beta = -
      0.249; p = 0.013) positivity (beta = -0.345; p = 0.001) scores; fewer years of
      work (beta = -0.269; p <= 0.001); and being a medical or nursing professor (beta
      = 0.169; p = 0.016) predicts high work burnout. Low MCS predicts a high level of
      student burnout. Results suggest that the Italian version of the CBI is a
      reliable instrument. Further research should focus on the prevalence of burnout
      in academics.

PMID- 30096953
TI  - Next Generation Cancer Vaccines-Make It Personal!
AB  - Dramatic success in cancer immunotherapy has been achieved over the last decade
      with the introduction of checkpoint inhibitors, leading to response rates higher
      than with chemotherapy in certain cancer types. These responses are often
      restricted to cancers that have a high mutational burden and show pre-existing T
      cell infiltrates. Despite extensive efforts, therapeutic vaccines have been
      mostly unsuccessful in the clinic. With the introduction of next generation
      sequencing, the identification of individual mutations is possible, enabling the
      production of personalized cancer vaccines. Combining immune check point
      inhibitors to overcome the immunosuppressive microenvironment and personalized
      cancer vaccines for directing the host immune system against the chosen antigens
      might be a promising treatment strategy.

PMID- 30096956
TI  - Management of Invasive Fungal Infections in Adult Patients with Hematological
      Malignancies in Greece during the Financial Crisis: Challenges and
      Recommendations.
AB  - There are concerns that the financial crisis in Greece negatively affected the
      management of invasive fungal infections (IFIs) among patients with hematological
      malignancies (HM). A working group (WG) was formed to explore the situation and
      make recommendations. A questionnaire was created and distributed to physicians
      caring for patients with HM, to gather information in a standardized manner on
      prescribing physicians, patient characteristics, availability of diagnostics,
      antifungal treatment practices and the conditions and particularities of Greek
      hospitals. A total of 141 physicians from 36 hematology units and laboratories
      located in 26 Greek hospitals participated. Regarding hospitalization conditions,
      only 56% reported that their patients were treated in isolated single or double
      bed rooms, 22% reported availability of HEPA filters, 47% reported construction
      works in progress, and an alarming 18% reported the presence of birds on open
      windows. Regarding diagnosis, only 31% reported availability of biomarkers for
      diagnosis of IFIs, 76% reported that CT scans were performed in a timely fashion,
      42% reported prompt availability of broncho-alveolar lavage, and only 6%
      availability of therapeutic drug monitoring. Of concern, 26% of the responders
      reported non-availability of some antifungals. In conclusion, significant
      challenges exist for the optimal management of IFIs in patients with HM in
      Greece.

PMID- 30096955
TI  - What Drives Food Insecurity in Western Australia? How the Perceptions of People
      at Risk Differ to Those of Stakeholders.
AB  - Food insecurity is considered a "wicked" problem due to the highly complex and at
      times undefined casual factors. Although many stakeholders are working to address
      the problem, a possible divergence exists between their views on food insecurity
      and those of the people who are actually experiencing the problem. The purpose of
      this study was to investigate whether there was a difference between the opinions
      of those "at risk" and stakeholders. A total of seven focus groups (two
      stakeholder groups n = 10, five "at-risk" groups n = 34) and three interviews
      (stakeholders n = 3) were conducted to ascertain perceptions. Thematic analysis
      generated 329 (209 "at-risk" and 120 stakeholder) coded statements related to
      food insecurity drivers. Respondents were in agreement for the majority of
      factors, and limited income was considered the primary driver of food insecurity.
      However, there were notable deviations in the perceived importance of certain
      drivers, particularly around the price of food and the lack of food literacy.
      Differences in the perception of causes of food insecurity may in part be
      attributed to the varied role each group plays in working towards the resolution
      of the problem, either at the household or system level.

PMID- 30096957
TI  - Sulfated Metabolites of Flavonolignans and 2,3-Dehydroflavonolignans: Preparation
      and Properties.
AB  - Silymarin, an extract from milk thistle (Silybum marianum) fruits, is consumed in
      various food supplements. The metabolism of silymarin flavonolignans in mammals
      is complex, the exact structure of their metabolites still remains partly unclear
      and standards are not commercially available. This work is focused on the
      preparation of sulfated metabolites of silymarin flavonolignans. Sulfated
      flavonolignans were prepared using aryl sulfotransferase from Desulfitobacterium
      hafniense and p-nitrophenyl sulfate as a sulfate donor and characterized by high
      resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR). Their
      1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzothiazoline-6
      sulfonic acid) (ABTS), and N,N-dimethyl-p-phenylenediamine (DMPD) radical
      scavenging; ferric (FRAP) and Folin-Ciocalteu reagent (FCR) reducing activity;
      anti-lipoperoxidant potential; and effect on the nuclear erythroid 2-related
      factor 2 (Nrf2) signaling pathway were examined. Pure silybin A 20-O-sulfate,
      silybin B 20-O-sulfate, 2,3-dehydrosilybin-20-O-sulfate, 2,3-dehydrosilybin-7,20
      di-O-sulfate, silychristin-19-O-sulfate, 2,3-dehydrosilychristin-19-O-sulfate,
      and silydianin-19-O-sulfate were prepared and fully characterized. Sulfated 2,3
      dehydroderivatives were more active in FCR and FRAP assays than the parent
      compounds, and remaining sulfates were less active chemoprotectants. The sulfated
      flavonolignans obtained can be now used as authentic standards for in vivo
      metabolic experiments and for further research on their biological activity.

PMID- 30096958
TI  - Neutrophil Extracellular Traps as an Adhesion Substrate for Different Tumor Cells
      Expressing RGD-Binding Integrins.
AB  - Neutrophil extracellular traps (NETs), in addition to their function as a host
      defense mechanism, play a relevant role in thrombus formation and metastatic
      dissemination of cancer cells. Here we screened different cancer cell lines
      endogenously expressing a variety of integrins for their ability to bind to NETs.
      To this end, we used NETs isolated from neutrophil-like cells as a substrate for
      adhesion assays of HT1080, U-87 MG, H1975, DU 145, PC-3 and A-431 cells. Levels
      of alpha5, alphaIIb, alphav, beta1, beta3 and beta5 chains were determined by
      western blot analysis in all cell lines and levels of whole integrins on the
      plasma membrane were assessed by fluorescence-activated cell sorting (FACS)
      analysis. We found that high levels of alpha5beta1, alphavbeta3 and alphavbeta5
      enhance cell adhesion to NETs, whereas low expression of alpha5beta1 prevents
      cell attachment to NETs. Excess of cyclic RGD peptide inhibited cell adhesion to
      NETs by competing with fibronectin within NETs. The maximal reduction of such
      adhesion was similar to that obtained by DNase 1 treatment causing DNA
      degradation. Our findings indicate that NETs from neutrophil-like cells may be
      used as a substrate for large screening of the adhesion properties of cancer
      cells expressing a variety of RGD-binding integrins.

PMID- 30096959
TI  - Organotypic 3D Models of the Ovarian Cancer Tumor Microenvironment.
AB  - Ovarian cancer progression involves multifaceted and variable tumor
      microenvironments (TMEs), from the in situ carcinoma in the fallopian tube or
      ovary to dissemination into the peritoneal cavity as single cells or spheroids
      and attachment to the mesothelial-lined surfaces of the omentum, bowel, and
      abdominal wall. The TME comprises the tumor vasculature and lymphatics (including
      endothelial cells and pericytes), in addition to mesothelial cells, fibroblasts,
      immune cells, adipocytes and extracellular matrix (ECM) proteins. When generating
      3D models of the ovarian cancer TME, researchers must incorporate the most
      relevant stromal components depending on the TME in question (e.g., early or late
      disease). Such complexity cannot be captured by monolayer 2D culture systems.
      Moreover, immortalized stromal cell lines, such as mesothelial or fibroblast cell
      lines, do not always behave the same as primary cells whose response in
      functional assays may vary from donor to donor; 3D models with primary stromal
      cells may have more physiological relevance than those using stromal cell lines.
      In the current review, we discuss the latest developments in organotypic 3D
      models of the ovarian cancer early metastatic microenvironment. Organotypic
      culture models comprise two or more interacting cell types from a particular
      tissue. We focus on organotypic 3D models that include at least one type of
      primary stromal cell type in an ECM background, such as collagen or fibronectin,
      plus ovarian cancer cells. We provide an overview of the two most comprehensive
      current models-a 3D model of the omental mesothelium and a microfluidic model. We
      describe the cellular and non-cellular components of the models, the
      incorporation of mechanical forces, and how the models have been adapted and
      utilized in functional assays. Finally, we review a number of 3D models that do
      not incorporate primary stromal cells and summarize how integration of current
      models may be the next essential step in tackling the complexity of the different
      ovarian cancer TMEs.

PMID- 30096962
TI  - Sperm transport and storage and its relation to the annual sexual cycle of the
      female red-sided garter snake, Thamnophis sirtalis parietalis.
AB  - Female red-sided garter snakes (Thamnophis sirtalis parietalis) store sperm from
      both late-summer and spring matings. Before winter dormancy, sperm are stored in
      specialized furrows in the vaginal portion of the oviduct, 3-6 cm anterior to the
      vent. After 6 weeks in dormancy, the epithelial cells lining this vaginal region
      hypertrophy and stain strongly with periodic acid-Schiff (PAS). This PAS+
      epithelial border sloughs and associates with sperm. These aggregations of PAS+
      material, which will be referred to as carrier matrices, move anteriorly through
      the oviduct. After 20 weeks in dormancy, most sperm are found in specialized
      infundibular storage regions. Spring mating induces a rapid degeneration of
      winter-stored sperm. Stored sperm are evacuated from infundibular storage
      receptacles within 6 hours after mating. Yet sperm from the spring mating are not
      evident in the oviduct until 24 hours after mating. Carrier matrices begin to
      form at this time. At 48 hours after mating, sperm, often associated with carrier
      matrices, appear in the infundibulum. At 40 days after mating, most sperm have
      moved into infundibular storage receptacles. Evidence suggests that carrier
      matrices not only facilitate the transport of sperm anteriorly from vaginal to
      infundibular regions, but also function as nutritional stores.

PMID- 30096963
TI  - Setiferous structures of male coleoptera.
AB  - A scanning electron microscopy study was made of the male setiferous sex patches
      and analogous structures in 11 families of Coleoptera (Anthribidae, Bruchidae,
      Ciidae, Cleridae, Coccinellidae, Dermestidae, Leiodidae, Ptinidae, Staphylinidae,
      Tenebrionidae, and Ostomatidae). These secondary sexual characters appear to have
      several features in common including relatively long, often ridged, setae,
      cuticular ducts (frequently cribriform pore plates), and the production of a
      secretion. It is suggested that these structures may all be concerned with the
      production, release, and dissemination of pheromones.

PMID- 30096960
TI  - Ethanolic Extract of Origanum vulgare Suppresses Propionibacterium acnes-Induced
      Inflammatory Responses in Human Monocyte and Mouse Ear Edema Models.
AB  - Acne vulgaris (acne) is a common inflammatory skin disorder, and
      Propionibacterium acnes plays a major role in the development and progression of
      acne inflammation. Herbs possessing antimicrobial and anti-inflammatory activity
      have been applied as a medical option for centuries. In this study, we examined
      the suppressive effect of ethanolic oregano (Origanum vulgare) extract on live P.
      acnes-induced in vivo and in vitro inflammation. Following ethanol extraction of
      oregano leaves, four compounds with strong antioxidant activity, including
      rosmarinic acid, quercetin, apigenin, and carvacrol, were identified by high
      performance liquid chromatography. Using the mouse ear edema model, we
      demonstrated that ethanol oregano extracts (EOE) significantly suppressed P.
      acnes-induced skin inflammation, as measured by ear thickness (32%) and biopsy
      weight (37%). In a separate study, using the co-culture of P. acnes and human THP
      1 monocytes, EOE reduced the production of interleukin (IL)-8, IL-1beta and tumor
      necrosis factor (TNF)-alpha up to 40%, 37%, and 18%, respectively, as well as the
      expression of these three pro-inflammatory mediators at the transcriptional
      level. Furthermore, EOE inhibited the translocation of nuclear factor-kappa B (NF
      kappaB) into the nucleus possibly by inactivating toll-like receptor-2 (TLR2).
      The suppressive effect of EOE on live P. acnes-induced inflammatory responses
      could be due, in part, to the anti-inflammatory and antioxidant properties, but
      not the anti-microbial effect of EOE.

PMID- 30096964
TI  - Structure and cytochemistry of the silk glands of the mygalomorph spider
      Antrodiaetus unicolor (araneae, antrodiaetidae).
AB  - Dissection and a variety of absorption and fluorescent cytochemical methods have
      demonstrated that Antrodiaetus unicolor females have only one type of silk gland
      and spigot and, consequently, the simplest silk production system of any spider
      yet investigated histochemically. The small spherical to pear-shaped glands are
      grouped into four clusters, each cluster serving one of the four spinnerets. The
      spigots are long, slender, and slightly bent distally. Although all gland cells
      are structurally similar, each gland simultaneously produces two different
      secretory products, the secretion of the distal hemisphere being rich in basic
      protein and sulfhydryl groups, and the proximal hemisphere secretion being an
      acidic protein containing a high concentration of histochemically demonstrable C
      terminal carboxyl groups. The two products remain segregated as they pass through
      the duct, where the acidic protein forms a thin outer layer around a core of
      basic protein. It is suggested that this segregation may persist in the silk
      strand after it exits from the spigot and that the outer acidic protein may be an
      adhesive agent.

PMID- 30096961
TI  - In Vivo and In Vitro Anti-Arthritic Effects of Cardenolide-Rich and
      Caffeoylquinic Acid-Rich Fractions of Periploca forrestii.
AB  - Periploca forrestii Schltr. (P. forrestii) is a species used in Traditional
      Chinese Medicine (TCM) known as "Miao medicine", and has a long history of use in
      the treatment of rheumatism, rheumatoid arthritis (RA), and joint pain. The
      present study aimed to evaluate the anti-arthritis effects of the cardenolide
      rich and caffeoylquinic acid-rich fractions (CDLFs and CQAFs) of P. forrestii in
      collagen-induced arthritic (CIA) rats, and defined the mechanisms of therapeutic
      action in MH7A cells treated with TNF-alpha. Serum rheumatoid factor (RF), TNF
      alpha, IL-6, IL-1beta, PGE2, NO, SOD, and MDA were determined by ELISA or other
      commercially assay kits. Histopathological changes in ankle joint tissues were
      examined. The mRNA expressions of IL-1beta, IL-6, COX-2, and iNOS in MH7A cells
      were measured by qRT-PCR assays. In addition, the expressions of iNOS, COX-2, and
      p65 proteins, and the phosphorylation of IkappaBalpha, p38, ERK1/2, and JNK
      proteins in MH7A cells were analyzed by Western blot. The results showed that
      CDLF and CQAF could suppress the paw swelling in CIA rats at different doses (125
      mg/kg, 250 mg/kg, and 500 mg/kg). Histopathological examination suggests that the
      CDLF and CQAF significantly relieved the damage of the structure of the ankle
      joint in CIA rats. In addition, serum RF, TNF-alpha, IL-6, IL-1beta, PGE2, NO,
      and MDA were decreased, along with increased activity of serum SOD. Furthermore,
      CDLF and CQAF downregulated the expressions of IL-1beta, IL-6, COX-2, iNOS, and
      p65, and inhibited the phosphorylation of IkappaBalpha, p38, ERK1/2, and JNK in
      MH7A cells treated with TNF-alpha. These findings demonstrated that both CDLF and
      CQAF exhibited anti-arthritic activity, which might be associated with their
      inhibitory effects on the NF-kappaB and MAPK signaling pathways.

PMID- 30096965
TI  - Pattern development in palleal buds of botryllid ascidians: Relation between
      parent and its buds in their body axes.
AB  - In order to determine how the zooid pattern (normal or reversed bilateral
      asymmetry) is transmitted through asexual reproduction in botryllid ascidians,
      the axial relationship between a zooid and its palleal buds was observed in
      Symplegmo reptans, Metandrocarpa uedai, Polyandrocarpa misakiensis, and P.
      stolonifera. The bud axes developed in harmony with the parent axes, with both
      normal and reversed body patterns, so that (1) when buds are given off from the
      right (left) side of the parent, their distal side becomes the right (left) in
      the future zooids (coincidence of the anteroposterior axis), (2) the free surface
      of the developing buds, like the parent, becomes dorsal (the coincidence of
      dorsoventral axis), and (3) the heart (gut loop), which is an organ representing
      the bilateral asymmetry, arises on the distal side of the developing buds, when
      the buds are derived from the side where the parent heart (gut loop) was situated
      (coincidence of the transverse axis). This shows that the bud develops as if it
      knew the position on the parent lateral wall from which it has arisen, a
      phenomenon referred to as the parental lateral effect.

PMID- 30096966
TI  - Seasonal changes in the pituitary gland of the feral hawaiian mongoose (Herpestes
      auropunctatus).
AB  - The Hawaiian mongoose (Herpestes auropunctatus) is a seasonally breeding mammal
      whose pituitary gland resembles that of other Viverridae. Certain features, such
      as a prominent pars tuberalis interna and a double-layered pars intermedia
      forming a cup for the neurohypophysis, are unique. With the light microscope,
      five different cell types can be recognized in the pars distalis after staining
      with periodic acid-Schiff (PAS)-orange G. Two types of acidophils are seen, a
      small yellow-staining cell and a large angular orange cell. Two basophilic cells
      are also seen, one with fine PAS-positive cytoplasmic granules and the other with
      coarse PAS-positive granules in the cytoplasm. The last cell type seen is the
      chromophobe. Differential cell counts indicated an altered distribution of
      chromophils in the ventral pars distalis of the female mongoose with changing
      season and reproductive status, but the most striking change was a decreased
      percentage of basophils in the pars distalis during the nonbreeding season.

PMID- 30096967
TI  - Sorbic acid-induced differences in the ultrastructural development of oocytes in
      the microbially ectosymbiotic female of Xyleborus ferrugineus (fabr.)
      (coleoptera, scolytidae).
AB  - The ovaries of the beetle Xyleborus ferrugineus reared on standard sawdust diet
      with an without 0.08% sorbic acid added were examined for differences in
      ultrastructural development of the oocytes. Indications of vigorous yolk
      deposition are an extensive rough-surfaced endoplasmic reticulum (RER), numerous
      electron-dense secretory vesicles and a prominent nucleus in associated follice
      cells, and extremely electron-opaque material in the interfollicular cell spaces
      and the perioocytic area. After 6 days of feeding without added sorbic acid, a
      mature terminal oocyte is present in one of the two ovaries. This terminal oocyte
      at this mature stage contains yolk spheres and lipid bodies. However, the most
      mature oocyte in beetles reared on the standard sawdust diet to which 0.08%
      sorbic acid was added remained at a previtellogenic stage after 6 days of
      feeding. Titers of ecdysone in 6-day-old adult females reared on standard sawdust
      without and with 0.08% sorbic acid added were 534.64 +/- 20.93 S.D. pg/mg and
      39.94 +/- 14.71 S.D. pg/mg body weight, respectively.

PMID- 30096968
TI  - Rosette glands in the gills of the grass shrimp, Palaemonetes pugio. I.
      Comparative morphology, cyclical activity, and innervation.
AB  - Two types of exocrine rosette glands (called type A and type B), located in the
      gill axes of the grass shrimp Palaemonetes pugio, are described. The type A
      glands are embedded within the longitudinal median septum of the gill axes,
      whereas the type B glands typically project into the efferent hemolymph channels
      of the gill axes. Although both glands have certain common characteristics (i.e.,
      a variable number of radially arranged secretory cells, a central intercalary
      cell, and a canal cell that forms the cuticular ductule leading to the branchial
      surface), they differ in the following respects. The type B gland is innervated,
      but the type A gland is not; axonal processes, containing both granular (ca. 900
      1300 A) and agranular (ca. 450-640 A) vesicles, occur at a juncture between
      adjacent secretory cells and the central cell of the type B gland. The secretory
      cells of type A and type B glands differ in their synthetic potential and
      membrane specializations. These differences are more pronounced in well
      developed, mature glands, most frequently encountered in larger (24-28 mm, total
      length) grass shrimp, than in the underdeveloped, immature glands that are most
      abundant in smaller (14-18 mm, total length) grass shrimp. Thus, in mature
      glands, the secretory cells of the type A rosette glands are characterized by
      extensive RER, abundant Golgi, and numerous secretory granules, whereas the
      secretory cells of the type B gland are characterized by extensively infolded and
      interdigitated basal plasmalemmas and by the presence of numerous mitochondria.
      In general, both types of glands exhibit increased secretory activity soon after
      ecdysis. The central and canal cells in both glands seem to have a role in the
      modification of the secreted materials. The possible functions assigned to the
      type A gland and the type B gland include phenol-oxidase secretion and
      osmoregulation, respectively.

PMID- 30096969
TI  - Osteocranial development in the viviparous surfperch Amphistichus argenteus
      (pisces: Embiotocidae).
AB  - The development of the cranial and branchial skeleton of the surfperch
      Amphistichus argenteus, a member of the family Embiotocidae, is described, and
      phylogenetic and functional aspects of the skull development of this species are
      discussed. The earliest bones to appear are those dermal elements of the
      branchial skeleton involved with feeding, and the bones, both dermal and
      endochondral, located in the basicranial region of the neurocranium. These are
      followed by dermal bones associated with the lateral line system and finally by
      the remainder of the bones of the branchial skeleton and the cartilaginous bones
      of the otic capsules. The last bone to develop is the ethmoid.

PMID- 30096970
TI  - Pharyngeal mastication and food transport in the carp (Cyprinus carpio L.): A
      cineradiographic and electromyographic study.
AB  - Cyprinids constitute the largest fish family and are characterized by their
      pharyngeal teeth. The masticatory mechanism is still poorly understood. The
      complex of structures that determine the movements of pharyngeal teeth and
      chewing pad in the carp (Cyprinus carpio L.) is analyzed. Activities in 16 head
      muscles of a free-swimming carp were recorded. X-ray cinerecordings, synchronized
      with electromyograms, were made of the intake, transport, mastication, and
      deglutition of radiopaque food pellets. Metal markers allowed a detailed movement
      analysis. Masticatory cycles are bilaterally synchronous and show distinct
      crushing and grinding patterns. Direct masticatory muscles that suspend and
      connect the pharyngeal bones steer and stabilize the masticatory movements.
      Baudelot's ligament, between skull and pectoral girdle, is applied as fulcrum,
      effects a crucial shift of the rotation axis of the pharyngeal jaw, and
      transforms crushing into grinding; simultaneous abduction lengthens the grinding
      stroke. Body muscles supply indirectly the power for mastication; they also
      appear to be regulated more distantly. The epaxial muscles lift the skull and
      thereby the levators of the pharyngeal bones, thus transmitting high forces to
      the teeth. They also stretch the levator of the bone as soon as occlusion is
      reached and thus optimize its production of forces during grinding. The hypaxial
      muscles retract the pharyngeal bones indirectly during grinding and power the
      teeth in sliding. The chewing pad, previously assumed to be motionless, rotates
      rostroventrad with the skull and intensifies grinding. Respiration and
      mastication are mutually related. The extensive movements of the pharyngeal bones
      are permitted only by the simultaneous expansion of the buccopharynx and a slide
      coupling in the branchial floor. Muscular pads that line the pharynx are shown to
      transport food toward the teeth. The constrictor pharyngis effects deglutition.
      Natural food, intestinal contents, and feces of the carp were analyzed with
      respect to the capacity for distinct masticatory operations. During the
      experiments pellets, barley, and worms were fed. The carp is specialized for
      polyphagy and this appears to be based on the profiles of the heterodont teeth
      rather than on drastic changes in the two preprogrammed activity patterns.
      Comparison of the pharyngeal jaw system in the carp and higher teleosts
      emphasizes the structural design for the application of large forces in this
      cyprinid.

PMID- 30096971
TI  - Rosette glands in the gills of the grass shrimp Palaemonetes pugio. II. Premolt
      ductule reformation: Replacement of ciliary processes by cytoplasmic processes in
      relation to gland maturation.
AB  - The events associated with premolt reformation of the cuticularized ductule in
      the underdeveloped (immature) branchial rosette glands, which are common in the
      gills of small (14-18 mm, total length) grass shrimp, are described and
      contrasted with the events of ductule reformation in the fully developed (mature)
      resette glands most common in larger shrimp. In immature rosette glands, two
      ciliary processes emerge from each of the component secretory cells and ascend
      into the basal luminal region of the old ductule. Subsequently a new ductule is
      formed around the old ductule, and the ciliary processes disappear, either
      because of degeneration or retraction. The transitory ciliary processes appear to
      prevent the old ductule from collapsing during the formation of a new ductule.
      Such transitory ciliary processes, however, are not found in association with
      premolt ductule reformation in the mature rosette glands; in their place are seen
      a number of microvilli-like cytoplasmic processes, which emanate from the apices
      of the secretory cells and from the channels of the central cell. These
      cytoplasmic processes in mature glands, like the ciliary processes in immature
      glands, are transitory and appear to prevent the collapse of the old ductule.
      Cytoplasmic processes comparable to those in mature glands, but relatively few in
      number and originating only from the secretory cells, are seen together with
      ciliary processes in some immature glands. The relative abundance of cytoplasmic
      processes in the mature glands, coupled with the observation that transitory
      ciliary processes occur in immature glands but not in mature glands, suggests
      that, during glandular maturation, transitory ciliary processes are replaced by
      transitory cytoplasmic processes.

PMID- 30096972
TI  - Structure of the shell from eggs of the tuatara, Sphenodon punctatus.
AB  - Shells from eggs of the tuatara (Sphenodon punctatus) are 0.2 mm thick and are
      composed of a layer of calcite and a multi-layered, fibrous shell membrane. Most
      of the calcareous layer is composed of roughly circular columns of crystalline
      material that extend deep into the shell membrane. The crystalline matrix of the
      columns is interwoven with fibers of the shell membrane except near the outer
      surface of the eggshell, where the calcareous material is more compact. Overlying
      the columns is a granular layer composed of blocks of crystalline material of
      random size, shape, and orientation. Disruption of this granular layer, perhaps
      through swelling of the eggs or as a result of environmental factors, gives the
      outer surface of the eggshell a coarse, weathered appearance. Removal of the
      calcareous material with a decalcifying agent shows that the outer surface of the
      shell membrane is composed of a meshwork of small fibers bound together by an
      amorphous matrix. No matrix was observed in inner layers of the shell membrane,
      and the fibers of these inner layers are arranged somewhat more regularly than
      the outer fibers. No structure comparable to the central cores of avian and
      certain chelonian eggs was observed in eggshells of the tuatara.

PMID- 30096973
TI  - The cellular basis of the aggressive acrorhagial response of sea anemones.
AB  - Some sea anemones possess structures called acrorhagi at the base of the
      tentacles. The acrorhagi are utilized solely for aggression. Acrorhagial
      aggression involves very exquisite intra- and interspecific recognition. This
      study examined acrorhagi and putative acrorhagial analogues or homologues in four
      species of sea anemone. The morphology and ultrastructure of tentacles,
      pseudoacrorhagi, column vesicles, and verrucae (adhesive column vesicles)
      differed from that of acrorhagi. Coral capitate tentacles and acrorhagi have
      different surface morphology, nematocysts, and functions. Besed on morphology,
      acrorhagi seem more likely to be homologous to tentacles than to verrucae.
      Acrorhagial nematocyst discharge and ectodermal peeling, the culmination of the
      response, were shown to require prior acrorhagial expansion in Anthopleura krebsi
      and Bunodosoma cavernata. A mechanical mechanism is suggested where- by
      distention of the acrorhagus opens a ciliary pit on the nematocyte surface and
      exposes the pit wall and microvilli, which may contain the chemoreceptors for the
      peeling process, including nematocyst discharge. A similar system may also be
      responsible for changing the threshold of nematocyst discharge in sea anemone
      tentacles. A case of possible neurosecretion in an anthozoan was also shown in
      this study.

PMID- 30096974
TI  - Structure and development of the larval visual system in embryos of Lytta
      viridana leconte (coleoptera, meloidae).
AB  - At hatching (252-264 hr. at 25 +/- 0.5 degrees C), the visual system in larvae of
      Lytta viridana consists of paired stemmata, stemmatal nerves, optic neuropiles,
      and inner and outer imaginal optic lobe anlagen. It originates between 64 and 72
      hr. with invagination of an optic lobe primordium in the side of each
      protocephalic lobe. These primordia later differentiate into protocerebral
      ganglion cells and the imaginal optic lobe anlagen. Each stemma arises at 72 hr.
      from epidermis below and behind the optic lobe invagination and subsequently
      becomes cupshaped, closes over, and differentiates. At hatching, it consists of a
      planoconvex corneal lens, a corneagenous layer, and an everse retina of numerous,
      pigmented retinular cells, each with a terminal rhabdomere. Between 96 and 104
      hr, proximal ends of the retinular cells grow posteromedially into a transverse,
      horizontal fold in the posterior wall of each optic lobe invagination and along
      its length to the protocerebral neuropile, which they contact by 112 hr. As the
      brain withdraws posteriorly within the head, these axons elongate
      correspondingly. Sheath cells of stemmata and stemmatal nerves descend either
      from protocerebral perineurium or the optic lobe primordia. Structure and
      development of the larval visual system in L. viridana are compared with those of
      other insects and its various components are shown to be homologous throughout
      the Insecta. However, the stemmata of this insect more closely resemble the
      atypical imaginal eyes of male scale insects than the photoreceptors of other
      holometabolous larvae-a similarity arising through convergence.

PMID- 30096975
TI  - Structure and evolution of tetraodontoid teeth: An autoradiographic study
      (pisces, Tetraodontiformes).
AB  - For years teeth of tetraodontoid fishes generally have been considered coalescent
      even though "coalescence," which also is found in fishes of other families, has
      never been well defined. This paper deals with some aspects of coalescence of the
      teeth in tetraodontoids and attempts to define this condition. The sites of
      osteodentinogenesis and the mechanisms by which hard tissues are formed,
      reabsorbed, and abraded during feeding were analyzed from semiserial decalcified
      sections and from ground sections, as well as from autoradiographs of the
      premaxilla and dentary bones of Sphoeroides greeleyi. The observations reported
      here, taken together with other data we have obtained on members of the
      Tetraodontoidei, permit clear definitions of "tooth" and "supporting bone," and
      consequently the structural meaning of coalescence. From these data we
      hypothesize how coalesced masticatory structures may have evolved in this group.

PMID- 30096976
TI  - Terminal degeneration in the mediodorsal cerebral cortex of the lizard Agama
      agama: Light and electron microscopy.
AB  - The degeneration of axon terminals in the small-celled part of the mediodorsal
      cortex (sMDC) of the lizard Agama agama has been studied after lesions in the
      dorsal cortex at various survival periods. The Fink-Heimer stain was used to map
      and demonstrate terminal degeneration with the light and electron microscope.
      Electron microscopy was used to identify and describe degenerating boutons
      ultrastructurally. One sham-operated and three unoperated animals served as
      controls. Between 6 and 21 days postsurgically, degenerating terminals can be
      seen through 80% of the superficial plexiform layer, the zone adjacent to the
      cellular layer remaining free of degeneration. Swelling of dendrites in the outer
      part of the superficial plexiform layer and increased numbers of vacuolar
      invaginations, both present at short (24 hr-6 days; peak at 48-54 hr) survival
      periods, can be regarded as reaction to the surgical trauma. Degeneration of axon
      terminals takes three forms, all of the electron-dense type: gray boutons,
      degenerating bouton-dendritic spine complexes surrounded or engulfed by glia, and
      degeneration debris inside glial processes. Several forms of terminal
      degeneration occur concomitantly at any short (3-12 days) survival time. At
      longer survival times (15-21 days) only debris is present. From 6 days on,
      considerable numbers of degenerating structures are present, but the majority of
      degenerating boutons and debris are associated with reactive glia rather than
      with dendrites. From these observations it is concluded that in this lizard
      application of the combined degeneration-Golgi-EM technique would probably lead
      to little success. Electron microscopy of Fink-Heimer-stained sections suggests
      that degenerating bouton-dendritic spine complexes and degeneration debris
      accumulate silver particles, whereas gray boutons do not.

PMID- 30096977
TI  - The cranial osteology and hyolaryngeal apparatus of Rhinophrynus dorsalis (Anura:
      Rhinophrynidae) with comparisons to recent pipid frogs.
AB  - The cranial osteology (including the hyolaryngeal apparatus) of Rhinophrynus
      dorsalis (Anura: Rhinophrynidae) is described from whole skeletons and serial
      cross sections. Some unique features of the extensively ossified skull include
      the enlarged and protracted olfactory region, for which the nasals form part of
      the septum nasi; the relatively short maxillaries and broad premaxillaries, and
      the immense quadratojugal; the extreme forward position of the quadrate; the lack
      of a firm articulation of the pterygoid and quadrate with the neurocranium and
      crista parotica; the quadrate lacking the distinct processes typical of other
      frogs; a single foramen for Nn. II-VII; a large, distinct operculum; and a
      bipartite hyale. Rhinophrynus shares other unusual cranial characteristics with
      the other pipoid frogs, Xenopus, Pipa, Hemipipa, and Hymenochirus. Among these
      features are the presence of a single frontoparietal in the adult, and the
      absence of parasphenoid alae, palatines, and mentomeckelian bones. Rhinophrynus
      differs from the pipids in the lack of a columella and a palatine process on the
      premaxilla, and in the possession of a quadratojugal, parahyoid bone, paired
      prevomers, olfactory eminence, massive quadrate that lacks distinguishable
      processes, a modified squamosal, and a bipartite hyale. Although the cranium of
      Rhinophrynus is distinctive, the evolutionary significance of its unusual
      features will remain obscure until comparable data are gathered from other
      closely related groups, the Discoglossoidea and the Pelobatoidea.

PMID- 30096978
TI  - The body surface of Branchiobdella pentodonta whit. (annelida, oligochaeta)
      examined by scanning microscopy.
AB  - The body of Branchiobdella pentodonta is uniformly covered with cuticular
      microvilli and abounds in sensory receptors. Muscle attachments are clearly
      visible both on the prostomium and trunk (11 segments). The mouth opening,
      oriented dorsally with respect to the adhesive sucker disk, possesses papillae
      with apical notches. On all trunk segments except the last three, which form the
      posterior sucker, mucous gland pores are evident. The nephridia open on the 3rd
      and 8th segments. On the more turgid sexual segments (5th, 6th, 7th) the
      spermathecal, atrial, and oviductal openings are seen. The 6th and 7th also
      contain the clitellum gland pores. The posterior sucker is delimited by a thick
      ring and the adhesive disk, and like the anterior disk is completely covered with
      the gland complex pores. The anal opening is on the 9th segment dorsal to the
      sucker. Based on these studies, we believe that the family Branchiobdellidae
      should be removed from the Oligochaeta and raised in rank to form a separate
      group.

PMID- 30096979
TI  - The conjugation junction of Tetrahymena: Its structure and development.
AB  - The conjugation junction of Tetrahymena has been examined by thin sections,
      freeze fracture preparations, and by scanning electron microscopy. The junction
      is formed where the anterior tips of the pairing cells attach to one another. The
      structure is essentially a large disk composed of two face-to-face plasma
      membranes separated by a gap of extracellular space measuring about 50 nm. Rows
      of intramembrane particles are present at the boundary between the junction and
      ordinary cell cortex. These particles form a ring around the junction. Subjacent
      to each membrane is a thick mottled layer of material. Pores form in the junction
      at sites of membrane fusion. Though wider than long, these structures are
      actually bridges of cytoplasm that connect the conjugating cells. Pores fall into
      certain size and shape classes, indicating that membrane fusion is highly
      controlled in this system. At the level of the cytoplasmic bridge the submembrane
      material is compact and electron-dense. Changes in the structure of the
      epiplasmic layer have been monitored as the normal cortex is modified during tip
      transformation and through formation of the mature conjugation junction. Evidence
      is provided that the submembrane layer plays a significant role in the regulation
      of pore formation. This cytoskeletal structure may also limit the extent of
      membrane fusion, thus controlling the size of the cytoplasmic channels.

PMID- 30096980
TI  - Synthesis of the vitelline and chorionic membranes of an ichneumonid parasitoid.
AB  - A reduction in free ribosomes and increases in rough endoplasmic reticulum and
      Golgi complexes in follicle cells during oogenesis suggest their involvement in
      supplying precursor material for synthesis of the vitelline and chorionic
      membranes of the ichneumonid parasitoid Campoletis sonorensis. The inner region
      of the vitelline membrane is composed of a narrow band of electron-opaque
      material; an outer region adjacent to the chorion consists of overlapping,
      irregularly shaped laminae. The fully developed chorion can be divided
      morphologically into three distinct regions. Its inner region adjacent to the
      lamellar plates of the vitelline membrane is composed of a lamellar membrane
      exhibiting a regular periodicity of crossbands. The middle section is composed of
      longitudinal chambers, some of which contain particulate matter. The outer region
      consists of slender projections which extend perpendicularly from the chorion
      surface. A fine layer of fibrous material adheres to the projections. The
      possibility of a relationship between the presence of fibrous material on the
      surface of parasitoid eggs and the inactivation or inhibition of host immune
      systems is mentioned.

PMID- 30096981
TI  - Synganglial and neurosecretory morphology of female Ornithodoros parkeri (cooley)
      (acari: Argasidae).
AB  - Single esophageal and paired cheliceral, palpal, pedal (I-IV), and opisthosomal
      nerves enter the synganglion and form specific neuropilar ganglia. The ganglia
      are integrated by a complex series of commissures and connectives. Eighteen
      paraldehyde-fuchsin-positive neurosecretory regions, which vary greatly in size
      and amount of granular neurosecretory material, are each associated (one or more)
      with neuropilar ganglia. Presumably transport of neurosecretory materials to
      target tissues occurs through axonal pathways, perineurial-neural lamella
      associations, and the neurohemal retrocerebral organ complex.

PMID- 30096982
TI  - Random Planar Orientation in Liquid-Crystalline Block Copolymers with Azobenzene
      Side Chains by Surface Segregation.
AB  - Rodlike liquid-crystalline (LC) mesogens preferentially adopt a homeotropic
      orientation by excluded volume effects at the free surface in side-chain LC
      (SCLC) polymer films. The homeotropic orientation is not advantageous for in
      plane LC alignment processes. Surface segregation of polymers is the phenomenon
      in which one component with a low surface free energy covers the surface in a
      mixture of two or more polymers or a block copolymer film. In SCLC block
      copolymer films, the surface segregation structure induces a random planar
      orientation due to the formation of a microphase-separated interface parallel to
      the substrate via the covering of one of the segregated polymer blocks. This
      feature article focuses on the unique, random planar orientation induced by the
      surface segregation of SCLC block copolymer films with the photoresponsive
      azobenzene (Az) mesogenic group. A transition moment of the Az mesogens is
      parallel to the molecular long axis, and light irradiation is conducted
      perpendicular to the film surface in general photoreaction processes. Therefore,
      the homeotropic molecular orientation in the SCLC polymer systems with Az
      mesogenic units inhibits efficient photoreaction reorientations in thin films.
      The random planar orientations by the surface segregation of a coil block in SCLC
      block polymers provide efficient in-plane photoreorientation and photoswitching
      with LC hierarchical mesostructures, such as microphase-separated structures of
      SCLC block copolymers and laminated LC polymer films. On the other hand, surface
      segregated SCLC blocks form a high-density polymer LC brush layer with a random
      planar orientation by self-assembly, which exhibits efficient angular selective
      photoreactions. These approaches using the surface segregation of SCLC block
      copolymers are expected to offer new concepts for the LC photoalignment process
      for LC polymer devices.

PMID- 30096983
TI  - Spectral Library Search Improves Assignment of TMT Labeled MS/MS Spectra.
AB  - Tandem mass tag (TMT)-based liquid chromatography-tandem mass spectrometry (LC
      MS/MS) is a proven approach for large-scale multiplexed protein quantification.
      However, the identification of TMT-labeled peptides is compromised by the
      labeling during traditional sequence database searches. In this study, we aim to
      use a spectral library search to increase the sensitivity and specificity of
      peptide identification for TMT-based MS data. Compared to MS/MS spectra of
      unlabeled peptides, the spectra of TMT-labeled counterparts usually display
      intensified b ions, suggesting that TMT labeling can alter product ion patterns
      during MS/MS fragementation. We compiled a human TMT spectral library of 401,168
      unique peptides of high quality from millions of peptide-spectrum matches in tens
      of profiling projects, matching to 14,048 nonredundant proteins (13,953 genes). A
      mouse TMT spectral library of similar size was also constructed. The libraries
      were subsequently appended with decoy spectra to evaluate the false discovery
      rate, which was validated by a simulated null TMT data set. The performance of
      the library search was further optimized by removing TMT reporter ions and
      selecting an appropriate library construction method. Finally, we searched a
      human TMT data set against the spectral library to demonstrate that the spectral
      library outperformed the sequence database. Both human and mouse TMT libraries
      were made publicly available to the research community.

PMID- 30096984
TI  - Potassium hydroxide treatment of UV-curable polysiloxane-type polymer for
      reproducible enhancement of cell adhesion and survival.
AB  - Polysiloxanes have shown exquisite properties for fabrication of microstructures
      for various biomedical and biotechnological applications. Nevertheless, their
      biocompatibility in terms of cell adhesion and survival ability is controversial.
      A simple polysiloxane modifying procedure that reproducibly enhances cell
      adhesion was proposed. Sonication of the hybrid organic-inorganic polymer of
      polysiloxane type, Ormocomp, in potassium hydroxide (KOH)/ethanol solution
      enhanced adhesion and subsequent survival of a panel of four cell lines.
      Characterization of surface properties of untreated and KOH-treated Ormocomp
      coatings has revealed considerable negative charge of Ormocomp substrates based
      on measurements of zeta potentials. KOH treatment did not modify surface
      morphology as visualized by scanning electron microscopy, but it resulted in
      alteration in both chemical composition according to SIMS analysis and
      hydrophilicity evaluated by static water contact angles. The results suggest that
      the failure of the adherent cells to survive on Ormocomp coatings is related to
      cell adhesion. The negative surface charge of Ormocomp substrates may be one of
      the influencing factors; however, the modification of surface chemistry mediated
      by KOH and the resulting increase in hydrophilicity accompanied by modification
      of protein adsorption are more likely responsible for enhanced cell adhesion and
      survival on Ormocomp coatings. KOH treatment thus may serve as a simple, cost
      effective procedure modifying polysiloxane-type polymers that leads to
      reproducible enhancement of cell adhesion.

PMID- 30096985
TI  - Epidemiology, disease burden, and treatment challenges of ulcerative colitis in
      Africa and the Middle East.
AB  - INTRODUCTION: Ulcerative colitis is an idiopathic, chronic, inflammatory bowel
      disorder characterized by an unpredictable course of alternating cycles of
      relapse and remission. Traditionally viewed as a disease of Western countries,
      the prevalence of ulcerative colitis is reported to be increasing in the
      developing world. In these regions, there is the potential to further explore the
      etiology of the disease, mainly through genetic studies. With this in mind, we
      consider available data relating to the epidemiology, clinical manifestations,
      and disease course of ulcerative colitis in Africa and the Middle East. Current
      treatment approaches in these countries are also reviewed and discussed in the
      context of new, small molecule, orally administered therapies. Areas covered:
      Available data on the epidemiology, clinical manifestations, and risk factors of
      ulcerative colitis in Africa and the Middle East are reviewed using a PubMed
      database search. Expert commentary: Epidemiologic studies from African and Middle
      Eastern countries suggest disease trends similar to the West, and an important
      health and economic burden. The management of ulcerative colitis within these
      developing countries is challenging, with the need to improve early diagnosis,
      access to healthcare, and patient education, along with facilitation of access to
      treatment options and improvement of medication adherence.

PMID- 30096986
TI  - DNA replication roadblocks caused by Cascade interference complexes are
      alleviated by RecG DNA repair helicase.
AB  - Cascade complexes underpin E. coli CRISPR-Cas immunity systems by stimulating
      'adaptation' reactions that update immunity and by initiating 'interference'
      reactions that destroy invader DNA. Recognition of invader DNA in Cascade
      catalysed R-loops provokes DNA capture and its subsequent integration into CRISPR
      loci by Cas1 and Cas2. DNA capture processes are unclear but may involve RecG
      helicase, which stimulates adaptation during its role responding to genome
      instability. We show that Cascade is a potential source of genome instability
      because it blocks DNA replication and that RecG helicase alleviates this by
      dissociating Cascade. This highlights how integrating in vitro CRISPR-Cas
      interference and adaptation reactions with DNA replication and repair reactions
      will help to determine precise mechanisms underpinning prokaryotic adaptive
      immunity.

PMID- 30096987
TI  - Crowdsourcing for assessment items to support adaptive learning.
AB  - PURPOSE: Adaptive learning requires frequent and valid assessments for learners
      to track progress against their goals. This study determined if multiple-choice
      questions (MCQs) "crowdsourced" from medical learners could meet the standards of
      many large-scale testing programs. METHODS: Users of a medical education app
      (Osmosis.org, Baltimore, MD) volunteered to submit case-based MCQs. Eleven
      volunteers were selected to submit MCQs targeted to second year medical students.
      Two hundred MCQs were subjected to duplicate review by a panel of internal
      medicine faculty who rated each item for relevance, content accuracy, and quality
      of response option explanations. A sample of 121 items was pretested on clinical
      subject exams completed by a national sample of U.S. medical students. RESULTS:
      Seventy-eight percent of the 200 MCQs met faculty reviewer standards based on
      relevance, accuracy, and quality of explanations. Of the 121 pretested MCQs, 50%
      met acceptable statistical criteria. The most common reasons for exclusion were
      that the item was too easy or had a low discrimination index. CONCLUSIONS:
      Crowdsourcing can efficiently yield high-quality assessment items that meet
      rigorous judgmental and statistical criteria. Similar models may be adopted by
      students and educators to augment item pools that support adaptive learning.

PMID- 30096988
TI  - Acute effects of aerobic exercise performed with different volumes on strength
      performance and neuromuscular parameters.
AB  - : The aim of the present study was to investigate the acute effect of the aerobic
      exercise volume on maximum strength and strength-endurance performance; and
      possible causes of strength decrements (i.e. central and peripheral fatigue).
      Twenty-one moderately trained men were submitted to a maximal incremental test to
      determine anaerobic threshold (AnT) and maximum dynamic strength (1RM) and
      strength-endurance (i.e. total volume load [TV]) tests to determine their
      baseline strength performance. Following, subjects performed six experimental
      sessions: aerobic exercise sessions (continuous running at 90% AnT) with
      different volumes (3 km, 5 km or 7 km) followed by 1RM or strength-endurance test
      in the 45 degrees  leg press exercise. Maximum voluntary isometric contraction
      (MVIC), voluntary activation (VA) level, contractile properties, and
      electromyographic activity (root mean square [RMS]) of the knee extensor muscles
      were assessed before and after aerobic exercises and after strength tests. TV was
      lower after 5 km and 7 km runs than in the control condition (12% and 22%,
      respectively). Additionally, TV was lower after 7 km than 3 km (14%) and 5 km
      (12%) runs. MVIC, VA, RMS, and contractile properties were reduced after all
      aerobic exercise volumes (~8%, ~5%, ~11% and ~6-14%, respectively). Additionally,
      MVIC, VA, and contractile properties were lower after strength tests (~15%, ~6%,
      ~9-26%, respectively). In conclusion, strength-endurance performance is impaired
      when performed after aerobic exercise and the magnitude of this interference is
      dependent on the aerobic exercise volume; and peripheral and central fatigue
      indices could not explain the different TV observed. ABBREVIATIONS: 1RM: Maximum
      dynamic strength; AnT: Anaerobic threshold; Ca2+: Calcium; CO2: Carbon dioxide;
      CT: Concurrent training; K+: potassium; [La]: Lactate concentration; MVIC:
      Maximum voluntary isometric contraction; O2: Oxygen; Pi: inorganic phosphate; PT:
      Peak twitch torque; TPT: Time to peak twitch torque; 1/2 RT: Half relaxation
      time; RMS: Root mean square; RTD: Average rate of twitch torque development; SE:
      Strength-endurance; TV: Total volume load; VA: Voluntary activation; VO2: Oxygen
      uptake; VO2peak: Peak oxygen uptake.

PMID- 30096989
TI  - Tactical Knowledge, Decision-Making, and Brain Activation Among Volleyball
      Coaches of Varied Experience.
AB  - This study compared decision-making (DM) of experienced and novice volleyball
      coaches while measuring blood flow brain activation with functional near-infrared
      spectroscopy. We sampled 34 coaches (mean [ M] age of 32.5, standard deviation [
      SD] = 9.4 years) divided into two experience groups: (a) novice ( M = 2.8, SD =
      1.9 years) and (b) experienced (M = 19, SD = 7.2 years). We evaluated coaches' DM
      through their responses to video-based scenarios of attacks performed in the
      extremities of the net within the Declarative Tactical Knowledge Test in
      Volleyball. We found no significant DM differences between the two groups of
      coaches ( p = .063), though novice (vs. experienced) coaches showed greater blood
      flow of the prefrontal cortex when visualizing the game situations. While
      experienced coaches may have better prefrontal neural efficiency during DM in
      these situations, further research is needed to evaluate other cerebral areas;
      since blood flow is an indirect measure of neural efficiency, and activity in
      remaining cortical components was unknown in this study.

PMID- 30096990
TI  - Communication Apprehension About Death, Religious Group Affiliation, and
      Religiosity: Predictors of Organ and Body Donation Decisions.
AB  - Communication willingness has previously been identified as an important
      communication factor in influencing individuals' decisions to become an organ
      donor. Missing from this conversation is the role of communication apprehension
      about death and its impact on donation decisions. The purpose of this study was
      to examine the relationships between communication apprehension about death,
      religiosity, religious affiliation, and donation decisions. Three hundred and
      thirty-three individuals participated in an online survey. Findings suggest that
      communication apprehension about death, especially communication avoidance about
      death, negatively impact donation decisions. In addition, religiosity and
      affiliation with a specific religion also negatively impact donation decisions.
      These variables were also predictors of organ and body donation. The findings
      show a need for more research on what prevents conversations about donation. In
      addition, the stark difference between organ donation likelihood and body
      donation likelihood underscores the need for communication scholars to examine
      communication about body donation.

PMID- 30096991
TI  - Behavioral Investments in the Short Term Fail to Produce a Sunk Cost Effect.
AB  - A cognitive bias known as the sunk cost effect has been found across a number of
      contexts. This bias drives the continued investment of time, effort, or money
      into an endeavor on the basis of prior investments into it. In Studies 1 and 2,
      we attempted to observe whether this effect occurs for short-term behavioral
      investments. In both studies, a reverse, or no sunk cost effect was found. In
      Study 3, we attempted to find an effect using hypothetical scenarios that were
      analagous to the behavioral investments presented in Study 1. This also failed to
      reveal an effect. Finally, Study 4 was an attempt to replicate a previously used
      hypothetical investment scenario; with results this time revealing the effect. A
      number of explanations for this pattern of results, such as participation and
      salient physical exertion, are discussed, with the possibility that some short
      term behavioral investments are not subject to the sunk cost effect.

PMID- 30096992
TI  - Adsorption process of tetrachloroethylene (PCE) on network growth ring.
AB  - This study was undergone to investigate the adsorption characteristics of
      tetrachloroethylene (PCE) on water supply network growth ring. According to the
      chemical composition of real network growth ring, iron oxide mixture containing
      synthesized goethite and lepidocrocite was applied as simulated growth ring. The
      results demonstrate that competition could take place only between PCE and the co
      present organic non-ionic compound, while inorganic salt had no discernible
      effect on PCE adsorption. A maximum adsorption capacity of 33.118 mg g-1 at
      equilibrium was achieved. By the non-linear regression method, the equilibrium
      adsorption data fitted well with the Freundlich isotherm model (R2 = 0.994), and
      the kinetic data obeyed pseudo-first order model (R2 = 0.985). Thermodynamic
      tests indicate the spontaneous and exothermic nature of adsorption process. In
      addition, no significant variation between the FTIR spectra of the iron oxide
      mixture before and after adsorption was observed, which verifies that hydrogen
      bonds between PCE and mineral mixture could be neglected. An overview of the
      experimental results leads to the conclusion that the adsorption of PCE onto the
      simulate growth ring was driven by dispersion and hydrophobic interactions. As a
      case study, this work will provide some information about water supply securit
      protection.

PMID- 30096993
TI  - Social and emotional loneliness in Korsakoff's syndrome.
AB  - INTRODUCTION: Loneliness is the subjective negative evaluation of social
      participation and isolation. Emotional loneliness reflects the absence of close
      relationships, and social loneliness the absence of a social network. Although
      loneliness is a growing problem in modern society, studies about loneliness in
      patients with Korsakoff's syndrome (KS) in need of chronic care are currently
      missing. METHODS: Sixty-three KS patients in long-term care and their primary
      caregivers reported loneliness of the patients on the De Jong Gierveld Loneliness
      Scale. RESULTS: A majority of KS patients reliably reported to feel lonely on
      both a social and emotional level of loneliness. The caregiving professionals
      rated loneliness of the patients even higher. Patients that had stayed in the
      clinic for a longer time tended to report less social loneliness, while
      caregivers reported less emotional loneliness in those patients. The KS-specific
      neuropsychiatric symptom of confabulations and a lack of social visits had a
      negative impact on social loneliness as perceived by the caregivers. CONCLUSION:
      Loneliness is a large problem in patients with KS that live in a long term care
      facility. Social loneliness can be positively influenced by creating
      possibilities to interact with other people, although the severity of the
      neuropsychiatric aspects of KS could compromise the presence of those
      interactions.

PMID- 30096994
TI  - The impact of past behaviour normality on regret: replication and extension of
      three experiments of the exceptionality effect.
AB  - Norm theory (Kahneman, D., & Miller, D. T. (1986). Norm theory: Comparing reality
      to its alternatives. Psychological Review, 93, 136-153) described a tendency for
      people to associate stronger regret with a negative outcome when it is a result
      of an exception (abnormal behaviour) compared to when it is a result of routine
      (normal behaviour). In two pre-registered studies, we conducted a replication and
      extension of three classic experiments on past behaviour exception/routine
      contrasts (N = 684). We successfully replicated Kahneman and Miller's (1986)
      experiments with the classic hitchhiker-scenario (Part 1) and car accident
      scenario (Part 2). In both cases, participants examined negative outcomes and
      tended to indicate a protagonist who deviated from own past behaviour as more
      regretful than another who followed routine. Pre-registered extensions also
      showed effects for ratings of social norms, negative affect, and perceived luck.
      We did not find support for the Miller, D. T., and McFarland, C. [(1986).
      Counterfactual thinking and victim compensation: A test of norm theory.
      Personality and Social Psychology Bulletin, 12, 513-519] experiment robbery
      scenario (Part 3) using a compensation measure, in that compensation to a victim
      of a robbery was not significantly different comparing exceptional and routine
      circumstances. However, a pre-registered extension showed that robbery under
      exceptional circumstances was perceived as more regretful than robbery under
      routine circumstances. We discuss implications for current and future research.

PMID- 30096995
TI  - Six-month evaluation of novel bioabsorbable scaffolds composed of poly-L-lactic
      acid and amorphous calcium phosphate nanoparticles in porcine coronary arteries.
AB  - Objective Using coronary angiography and intravascular ultrasound methods to
      evaluate the performance of the novel fully bioabsorbable scaffold (NFBS)
      composed of poly-L-lactic acid/amorphous calcium phosphate (PLLA/ACP) at six
      month follow-up by comparing with PLLA scaffolds Methods Twelve PLLA/ACP
      scaffolds and 12 PLLA scaffolds were implanted into the coronary arteries of 12
      miniature pigs. Quantitative coronary angiography (QCA) was used to measure the
      reference vessel diameter (RVD), mean lumen diameter (MLD) and late lumen loss
      (LLL). According to IVUS images, we calculated the strut malapposition rate (SMR)
      at post implantation, strut overlap rate (SOR), reference vessel area (RVA), mean
      stent area (MSA), mean lumen area (MLA) and luminal patency rate (LPR) at six
      month follow-up. The radial strength of the scaffold was evaluated using a
      catheter tensile testing machine. Results QCA results indicated that, at six
      month, MLD of PLLA/ACP scaffolds was greater than those of PLLA scaffolds (2.47
      +/- 0.22 mm vs. 2.08 +/- 0.25 mm, P < 0.05); LLL of PLLA/ACP scaffolds was less
      than those of PLLA scaffolds (0.42 +/- 0.20 mm vs. 0.75 +/- 0.22 mm, P < 0.05).
      IVUS results showed the SMR and SOR were all significantly less with the PLLA/ACP
      scaffolds than the PLLA scaffolds (5.84% +/- 3.56% vs. 17.72% +/- 4.86%, P <
      0.05) (6.17% +/- 4.63% vs. 17.65% +/- 4.29%, P < 0.05). MSA, MLA and LPR of the
      PLLA/ACP scaffolds were all greater than those of PLLA scaffolds (6.35 +/- 0.45
      mm2 vs. 5.35 +/- 0.51 mm2, P < 0.05) (4.76 +/- 0.46 mm2 vs. 3.77 +/- 0.46 mm2, P
      < 0.05) (78.01% +/- 12.29% vs. 61.69% +/- 9.76%, P < 0.05). Radial strength of
      PLLA/ACP scaffold at six month was greater than that of PLLA scaffold (76.33 +/-
      3.14 N vs. 67.67 +/- 3.63 N). Conclusion The NFBS had less stent recoil, better
      lumen patency rate and greater radial strength than PLLA scaffolds. The results
      suggest the NFBS scaffolds can maintain the structural strength and functional
      performance, which are effective for up to six months when implanted in porcine
      coronary arteries.

PMID- 30096996
TI  - Alginate/poly(amidoamine) injectable hybrid hydrogel for cell delivery.
AB  - A covalently cross-linked injectable hybrid hydrogel, namely,
      alginate/poly(amidoamine) (PAMAM), with the objective of cell delivery was
      innovatively designed and synthesized using tetra-amino-functional PAMAM
      dendrimer as the cross-linker. With the increase in percentage of PAMAM cross
      linker, the pore size and swelling ratio of hydrogels were in the range of 57 +/-
      18 MUm to 88 +/- 25 MUm and 110 +/- 16 to 157 +/- 20, respectively. The study of
      attachment and proliferation of MC3T3-E1 pre-osteoblasts using 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay through indirect and
      direct contact methods indicated a continuous increase in metabolically active
      live cells with time, implying non-cytotoxicity of the synthesized hydrogel. The
      live-dead assay showed >95% of live cells for alginate/PAMAM hydrogels,
      suggesting viability of the encapsulated cells. When the percentage of PAMAM
      cross-linker in alginate/PAMAM hydrogel was increased from 5 to 25, the
      percentage degradation rate decreased from 1.1 to 0.29%/day. Given that the
      poly(ethylene glycol) is commonly used cross-linker for hydrogel syntheses, we
      compared the behavior with poly(ethylene glycol). The incorporation of
      poly(ethylene glycol) in alginate/PAMAM hydrogel reduced the activity of MC3T3-E1
      cells and their viability compared to the alginate/PAMAM hydrogels. The
      protonation of amino groups in alginate/PAMAM injectables under physiological
      conditions led to the formation of cationic hydrogels. These cationic hydrogels
      showed enhanced cell encapsulation and attachment ability because of
      electrostatic interaction with negatively charged cell surface as determined by
      cell adhesion and extensions from scanning electron microscope and vinculin assay
      and ability of in situ calcium phosphate mineralization. These observations point
      toward the potential use as an injectable scaffold for cell delivery and tissue
      engineering applications.

PMID- 30096997
TI  - Graphene oxide-hydroxyapatite nanocomposites effectively deliver HSV-TK suicide
      gene to inhibit human breast cancer growth.
AB  - Gene therapy with herpes simplex virus thymidine kinase gene (HSV-TK), which is
      also known as "suicide" gene therapy, is effective in various tumor models. The
      lack of a safe and efficient gene delivery system has become a major obstacle to
      "suicide" gene therapy. In this study, the cytotoxicity and transfection
      efficiency of graphene oxide-hydroxyapatite (GO-Hap) were analyzed by MTS and
      flow cytometry, respectively. A series of assays were performed to evaluate the
      effects of GO-HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment on growth
      of human breast normal and cancer cells. The results showed that GO-HAp
      nanocomposites effectively transfected cells with minimum toxicity. GO-HAp/p
      HRE/ERE-Sur-TK combined with ganciclovir treatment inhibited the proliferation
      and induced cell apoptosis in cancer cells, while the cytotoxic effects are
      tolerable in normal breast cells. We conclude that the GO-HAp nanocomposites have
      significant potential as a gene delivery vector for cancer therapy.

PMID- 30096998
TI  - Hemostatic properties of in situ gels composed of hydrophobically modified
      biopolymers.
AB  - Hemorrhaging often occurs during cardiac surgery, and postoperative bleeding is
      associated with medical complications or even death. Medical complications
      resulting from hemorrhaging can lead to longer hospital stays, thus increasing
      costs. Hemostatic agents are the main treatment for bleeding. In the present
      study, hemostatic agents composed of aldehyde groups and hydrophobically modified
      with hyaluronic acid (ald-hm-HyA) and hydrophobically modified gelatin (hm
      ApGltn) were developed and their hemostatic effects were evaluated. These
      modified hemostatic agents formed more stable blood clots compared with the
      nonhydrophobically modified HyA-based hemostatic agent. The bulk strength of the
      whole blood clot using the aldehyde and stearoyl group-modified hyaluronic acid
      (ald-C18-HyA)/hm-ApGltn-based hemostatic agent was higher than that of the
      aldehyde group only modified HyA (ald-HyA)/hm-ApGltn-based hemostatic agent.
      Rheological experiments using alpha-cyclodextrin showed that hydrophobic
      modification of HyA with C18 groups effectively enhanced anchoring to the red
      blood cell surface. Therefore, the ald-hm-HyA/hm-ApGltn-based hemostatic agent
      has potential applications in cardiac surgery.

PMID- 30097000
TI  - Regarding Medical Assistance in Dying and Mental Health: A Legal, Ethical, and
      Clinical Analysis.

PMID- 30096999
TI  - Physical properties and biocompatibility effects of doping SiO2 and TiO2 into
      phosphate-based glass for bone tissue engineering.
AB  - Phosphate glass is continuing to gain more attention as potential bone
      substitutes. The ternary (P2O5-CaO-Na2O) is investigated in terms of both
      physical properties and biocompatibility by doping different percentages of SiO2
      and TiO2. Two groups were prepared; the first has different percentages of TiO2
      and SiO2, whereas the second group compositions have 5 mol% TiO2 and 5 mol% SiO2
      being added to compensate the network-forming oxide P2O5 and the network
      modifying oxide CaO. Density, mass loss, pH, DTA, XRD, and cation release
      experiments were performed to study the physicochemical properties of the
      compositions, while MG63 and hMS cells were used within in vitro cell culture to
      study their biocompatibility. Results showed that an increase in TiO2 content
      correlated with an increase in glass density, decreased mass loss, increased
      trend of Tg and Tm values, and Na+ and Ca2+ release in group 1. There was no
      improvement in the MG63 viability or the ability of hMSCs to differentiate into
      osteoblasts where TiO2 decreased in favour of SiO2. Furthermore, in group 2,
      50P2O5-25CaO was less dense than 45P2O5-30CaO, degraded dramatically less, had
      lower Tg and Tm values and released less Na+ and Ca(2+). The synergistic effect
      of doping 5 mol% TiO2 and 5 mol% SiO2 increased the MG63 viability in both
      compositions and was found 45P2O5-30CaO to have promising results in terms of the
      ability of hMSCs to differentiate into osteoblasts. To conclude, substituting
      TiO2 in place of SiO2 improved the physical properties and the biocompatibility
      of (P2O5-CaO-Na2O) glass system, whereas doping 5 mol% SiO2 and 5 mol% TiO2
      together in place of P2O5 and CaO had a synergistic effect in controlling their
      degradation rate and improving their biological responses.

PMID- 30097001
TI  - Response to Comment Regarding: Medical Assistance in Dying and Mental Health: A
      Legal, Ethical, and Clinical Analysis.

PMID- 30097002
TI  - Collaborative Care or the Pinball Syndrome.

PMID- 30097003
TI  - Advancing Integrated Care through Psychiatric Workforce Development: A Systematic
      Review of Educational Interventions to Train Psychiatrists in Integrated Care.
AB  - OBJECTIVE: Integrated or collaborative care is a well-evidenced and widely
      practiced approach to improve access to high-quality mental health care in
      primary care and other settings. Psychiatrists require preparation for this
      emerging type of practice, and such training is now mandatory for Canadian
      psychiatry residents. However, it is not known how best to mount such training,
      and in the absence of such knowledge, the quality of training across Canada has
      suffered. To guide integrated care education nationally, we conducted a
      systematic review of published and unpublished training programs. METHOD: We
      searched journal databases and web-based 'grey' literature and contacted all
      North American psychiatry residency programs known to provide integrated care
      training. We included educational interventions targeting practicing
      psychiatrists or psychiatry residents as learners. We critically appraised
      literature using the Medical Education Research Study Quality Instrument
      (MERSQI). We described the goals, content, and format of training, as well as
      outcomes categorized according to Kirkpatrick level of impact. RESULTS: We
      included 9 published and 5 unpublished educational interventions. Studies were of
      low to moderate quality and reflected possible publication bias toward favourable
      outcomes. Programs commonly involved longitudinal clinical experiences for
      residents, mentoring networks for practicing physicians, or brief didactic
      experiences and were rarely oriented toward the most empirically supported models
      of integrated care. Implementation challenges were widespread. CONCLUSIONS:
      Similar to integrated care clinical interventions, integrated care training is
      important yet difficult to achieve. Educational initiatives could benefit from
      faculty development, quality improvement to synergistically improve care and
      training, and stronger evaluation. Systematic review registration number:
      PROSPERO 2014:CRD42014010295.

PMID- 30097004
TI  - miREM: an expectation-maximization approach for prioritizing miRNAs associated
      with gene-set.
AB  - BACKGROUND: The knowledge of miRNAs regulating the expression of sets of mRNAs
      has led to novel insights into numerous and diverse cellular mechanisms. While a
      single miRNA may regulate many genes, one gene can be regulated by multiple
      miRNAs, presenting a complex relationship to model for accurate predictions.
      RESULTS: Here, we introduce miREM, a program that couples an expectation
      maximization (EM) algorithm to the common approach of hypergeometric probability
      (HP), which improves the prediction and prioritization of miRNAs from gene-sets
      of interest. miREM has been made available through a web-server ( https://bioinfo
      csi.nus.edu.sg/mirem2/ ) that can be accessed through an intuitive graphical user
      interface. The program incorporates a large compendium of human/mouse miRNA
      target prediction databases to enhance prediction. Users may upload their genes
      of interest in various formats as an input and select whether to consider non
      conserved miRNAs, amongst filtering options. Results are reported in a rich
      graphical interface that allows users to: (i) prioritize predicted miRNAs through
      a scatterplot of HP p-values and EM scores; (ii) visualize the predicted miRNAs
      and corresponding genes through a heatmap; and (iii) identify and filter
      homologous or duplicated predictions by clustering them according to their seed
      sequences. CONCLUSION: We tested miREM using RNAseq datasets from two single
      "spiked" knock-in miRNA experiments and two double knock-out miRNA experiments.
      miREM predicted these manipulated miRNAs as having high EM scores from the gene
      set signatures (i.e. top predictions for single knock-in and double knock-out
      miRNA experiments). Finally, we have demonstrated that miREM predictions are
      either similar or better than results provided by existing programs.

PMID- 30097005
TI  - High resolution melting curve analysis enables rapid and reliable detection of
      G6PD variants in heterozygous females.
AB  - BACKGROUND: Like glucose-6-phosphate dehydrogenase (G6PD) deficient hemizygous
      males and homozygous females, heterozygous females could also manifest hemolytic
      crisis, neonatal hyperbilirubinemia or kernicterus upon exposure to oxidative
      stress induced by certain foods such as fava beans, drugs or infections. Although
      hemizygous males and homozygous females are easily detected by conventional G6PD
      enzyme assay method, the heterozygous state could be missed by the conventional
      methods as the mosaic population of both normal and deficient RBCs circulates in
      the blood. Thus the present study aimed to apply high resolution melting (HRM)
      curve analysis approach to see whether HRM could be used as a supplemental
      approach to increase the chance of detection of G6PD heterozygosity. RESULTS:
      Sixty-three clinically suspected females were evaluated for G6PD status using
      both enzyme assay and HRM analysis. Four out of sixty-three participants came out
      as G6PD deficient by the enzyme assay method, whereas HRM approach could identify
      nine participants with G6PD variants, one homozygous and eight heterozygous.
      Although only three out of eight heterozygous samples had G6PD enzyme deficiency,
      the HRM-based heterozygous G6PD variants detection for the rest of the samples
      with normal G6PD enzyme activities could have significance because their newborns
      might fall victim to serious consequences under certain oxidative stress.
      CONCLUSIONS: In addition to the G6PD enzyme assay, HRM curve analysis could be
      useful as a supplemental approach for detection of G6PD heterozygosity.

PMID- 30097008
TI  - The state of health services partnering with consumers: evidence from an online
      survey of Australian health services.
AB  - BACKGROUND: Involving consumers in producing health services is mandated in many
      countries. Evidence indicates consumer partnerships lead to improved service
      design, quality and innovation. Involving participants from minority groups is
      crucial because poor understanding of distinctive needs affects individuals'
      service experiences and outcomes. Few studies consider service compliance with
      consumer partnering requirements or inclusion of minority group participants.
      METHODS: An online survey structured by domains of the Australian National Safety
      and Quality in Health Service Standards (NSQHS, 2013), was conducted. Questions
      covered consumer partnering in service planning, management and evaluation plus
      patient care design and inclusion of consumers from minority groups.
      Approximately 1200 Australian hospital and day surgery services were identified
      and 447 individual email addresses were identified for staff leading consumer
      partnerships. Quantitative data were analysed using SPSS. Qualitative responses,
      managed in NVivo, were analysed thematically. Frequencies were produced to
      indicate common activities and range of activities within question domains.
      RESULTS: Comprehensive responses were received from 115 services (25.7%),
      including metropolitan and non-metropolitan, private and public service settings.
      Most respondents (95.6%) "partnered with consumers to develop or provide feedback
      on patient information". Regarding inclusion of participants from minority
      groups, respondents were least likely to specifically include those from socially
      disadvantaged backgrounds (23.6%). Public health services were more likely than
      private services to engage with consumers. CONCLUSIONS: The survey is the first
      to include responses about consumer partnering from across Australia. While many
      respondents partner with consumers, it is clear that more easily-organised
      activity such as involvement in existing committees or commenting on patient
      information occurs more commonly than involvement in strategy or governance. This
      raises questions over whether strategic-level involvement is too difficult or
      unrealistic; or whether services simply lack tools. Minority views may be missed
      where there is a lack of specific action to include diversity. Future work might
      address why services choose the activities we found and probe emerging
      opportunities, such as using social media or online engagement.

PMID- 30097007
TI  - In silico insights on diverse interacting partners and phosphorylation sites of
      respiratory burst oxidase homolog (Rbohs) gene families from Arabidopsis and
      rice.
AB  - BACKGROUND: NADPH oxidase (Nox) is a critical enzyme involved in the generation
      of apoplastic superoxide (O2-), a type of reactive oxygen species (ROS) and hence
      regulate a wide range of biological functions in many organisms. Plant Noxes are
      the homologs of the catalytic subunit from mammalian NADPH oxidases and are known
      as respiratory burst oxidase homologs (Rbohs). Previous studies have highlighted
      their versatile roles in tackling different kind of stresses and in plant growth
      and development. In the current study, potential interacting partners and
      phosphorylation sites were predicted for Rboh proteins from two model species (10
      Rbohs from Arabidopsis thaliana and 9 from Oryza sativa japonica). The present
      work is the first step towards in silico prediction of interacting partners and
      phosphorylation sites for Rboh proteins from two plant species. RESULTS: In this
      work, an extensive range of potential partners (unique and common), leading to
      diverse functions were revealed from interaction networks and gene ontology
      classifications, where majority of AtRbohs and OsRbohs play role in stress
      related activities, followed by cellular development. Further, 68 and 38
      potential phosphorylation sites were identified in AtRbohs and OsRbohs,
      respectively. Their distribution, location and kinase specificities were also
      predicted and correlated with experimental data as well as verified with the
      other EF-hand containing proteins within both genomes. CONCLUSIONS: Analysis of
      regulatory mechanisms including interaction with diverse partners and post
      translational modifications like phosphorylation have provided insights regarding
      functional multiplicity of Rbohs. The bioinformatics-based workflow in the
      current study can be used to get insights for interacting partners and
      phosphorylation sites from Rbohs of other plant species.

PMID- 30097006
TI  - Microevolutionary processes impact macroevolutionary patterns.
AB  - BACKGROUND: Macroevolutionary modeling of species diversification plays important
      roles in inferring large-scale biodiversity patterns. It allows estimation of
      speciation and extinction rates and statistically testing their relationships
      with different ecological factors. However, macroevolutionary patterns are
      ultimately generated by microevolutionary processes acting at population levels,
      especially when speciation and extinction are considered protracted instead of
      point events. Neglecting the connection between micro- and macroevolution may
      hinder our ability to fully understand the underlying mechanisms that drive the
      observed patterns. RESULTS: In this simulation study, we used the protracted
      speciation framework to demonstrate that distinct microevolutionary scenarios can
      generate very similar biodiversity patterns (e.g., latitudinal diversity
      gradient). We also showed that current macroevolutionary models may not be able
      to distinguish these different scenarios. CONCLUSIONS: Given the compounded
      nature of speciation and extinction rates, one needs to be cautious when
      inferring causal relationships between ecological factors and macroevolutioanry
      rates. Future studies that incorporate microevolutionary processes into current
      modeling approaches are in need.

PMID- 30097009
TI  - Correction to: Actigraphy assessments of circadian sleep-wake cycles in the
      Vegetative and Minimally Conscious States.
AB  - The original article [1] contains an error affecting the actigraphy time-stamps
      throughout the article, particularly in Table 1.

PMID- 30097011
TI  - Real-time tracking of complex ubiquitination cascades using a fluorescent
      confocal on-bead assay.
AB  - BACKGROUND: The ubiquitin-proteasome system (UPS) controls the stability,
      localization and/or activity of the proteome. However, the identification and
      characterization of complex individual ubiquitination cascades and their
      modulators remains a challenge. Here, we report a broadly applicable,
      multiplexed, miniaturized on-bead technique for real-time monitoring of various
      ubiquitination-related enzymatic activities. The assay, termed UPS-confocal
      fluorescence nanoscanning (UPS-CONA), employs a substrate of interest immobilized
      on a micro-bead and a fluorescently labeled ubiquitin which, upon enzymatic
      conjugation to the substrate, is quantitatively detected on the bead periphery by
      confocal imaging. RESULTS: UPS-CONA is suitable for studying individual enzymatic
      activities, including various E1, E2, and HECT-type E3 enzymes, and for
      monitoring multi-step reactions within ubiquitination cascades in a single
      experimental compartment. We demonstrate the power of the UPS-CONA technique by
      simultaneously following ubiquitin transfer from Ube1 through Ube2L3 to E6AP. We
      applied this multi-step setup to investigate the selectivity of five
      ubiquitination inhibitors reportedly targeting different classes of
      ubiquitination enzymes. Using UPS-CONA, we have identified a new activity of a
      small molecule E2 inhibitor, BAY 11-7082, and of a HECT E3 inhibitor, heclin,
      towards the Ube1 enzyme. CONCLUSIONS: As a sensitive, quantitative, flexible, and
      reagent-efficient method with a straightforward protocol, UPS-CONA constitutes a
      powerful tool for interrogation of ubiquitination-related enzymatic pathways and
      their chemical modulators, and is readily scalable for large experiments.

PMID- 30097010
TI  - Functionalization of stable fluorescent nanodiamonds towards reliable detection
      of biomarkers for Alzheimer's disease.
AB  - BACKGROUND: Stable and non-toxic fluorescent markers are gaining attention in
      molecular diagnostics as powerful tools for enabling long and reliable biological
      studies. Such markers should not only have a long half-life under several assay
      conditions showing no photo bleaching or blinking but also, they must allow for
      their conjugation or functionalization as a crucial step for numerous
      applications such as cellular tracking, biomarker detection and drug delivery.
      RESULTS: We report the functionalization of stable fluorescent markers based on
      nanodiamonds (NDs) with a bifunctional peptide. This peptide is made of a cell
      penetrating peptide and a six amino acids long beta-sheet breaker peptide that is
      able to recognize amyloid beta (Abeta) aggregates, a biomarker for the Alzheimer
      disease. Our results indicate that functionalized NDs (fNDs) are not cytotoxic
      and can be internalized by the cells. The fNDs allow ultrasensitive detection (at
      picomolar concentrations of NDs) of in vitro amyloid fibrils and amyloid
      aggregates in AD mice brains. CONCLUSIONS: The fluorescence of functionalized NDs
      is more stable than that of fluorescent markers commonly used to stain Abeta
      aggregates such as Thioflavin T. These results pave the way for performing
      ultrasensitive and reliable detection of Abeta aggregates involved in the
      pathogenesis of the Alzheimer disease.

PMID- 30097012
TI  - Glycemic control and healthcare utilization following pregnancy among women with
      pre-existing diabetes in Navajo Nation.
AB  - BACKGROUND: Native American communities experience greater burden of diabetes
      than the general population, including high rates of Type 2 diabetes among women
      of childbearing age. Diabetes in pregnancy is associated with risks to both the
      mother and offspring, and glycemic control surrounding the pregnancy period is of
      vital importance. METHODS: A retrospective chart review was conducted at a major
      Navajo Area Indian Health Service (IHS) hospital, tracking women with pre
      existing diabetes who became pregnant between 2010 and 2012. Logistic regression
      was performed to find patient-level predictors of our desired primary outcome
      having hemoglobin A1c (HbA1c) consistently < 8% within 2 years after pregnancy.
      Descriptive statistics were generated for other outcomes, including glycemic
      control and seeking timely IHS care. RESULTS: One hundred twenty-two pregnancies
      and 114 individuals were identified in the dataset. Baseline HbA1c was the only
      covariate which predicted our primary outcome (OR = 1.821, 95% CI = 1.184-2.801).
      Examining glycemic control among pregnancies with complete HbA1c data (n = 59),
      59% were controlled before, 85% during, and 34% after pregnancy. While nearly all
      women received care in the immediate postpartum period, only 49% of women visited
      a primary care provider and 71% had HbA1c testing in the 2 years after pregnancy.
      CONCLUSIONS: This is the first analysis of outcomes among women with diabetes in
      pregnancy in Navajo Nation, the largest reservation and tribal health system in
      the United States. Our findings demonstrate the positive impact of specialized
      prenatal care in achieving glycemic control during pregnancy, while highlighting
      the challenges in maintaining glycemic control and continuity of healthcare after
      pregnancy.

PMID- 30097013
TI  - Consequences of screening in cervical cancer: development and dimensionality of a
      questionnaire.
AB  - BACKGROUND: Cervical cancer screening will inevitably lead to unintentional
      harmful effects e.g. detection of indolent pathological conditions defined as
      overdetection or overdiagnosis. Overdiagnosis often leads to overutilisation,
      overtreatment, labelling and thereby negative psychosocial consequences. There is
      a lack of adequate psychosocial measures when it comes to measurement of the
      harms of medical screening. However, the Consequences of Screening questionnaire
      (COS) has been found relevant and comprehensive with adequate psychometric
      properties in breast and lung cancer screening. Therefore, the aim of the present
      study was to extend the Consequences of Screening Questionnaire for use in
      cervical cancer screening by testing for content coverage, dimensionality, and
      reliability. METHODS: In interviews, the suitability, content coverage, and
      relevance of the COS were tested on participants in cervical screening. The
      results were thematically analysed to identify the key consequences of abnormal
      screening results. Item Response Theory and Classical Test Theory were used to
      analyse data. Dimensionality, invariance, and reliability were established by
      item analysis, examining the fit between item responses and Rasch models.
      RESULTS: All COS items were found relevant by the interviewees and the ten COS
      constructs were confirmed each to be unidimensional in the Rasch models. Ten new
      themes specifically relevant for participants having abnormal cervical screening
      result were extracted from the interviews: 'Uncertainty about the screening
      result', 'Uncertainty about future pregnancy', 'Change in body perception',
      'Change in perception of own age', 'Guilt', 'Fear and powerlessness', 'Negative
      experiences from the pelvic examination', 'Negative experiences from the
      examination', 'Emotional reactions' and 'Sexuality' Altogether, 50 new items were
      generated: 10 were single items. Most of the remaining 40 items were confirmed to
      fit Rasch models measuring ten different constructs. However, the two items in
      the scale 'Change in perception of own age' both possessed differential item
      functioning in relation to time, which can bias longitudinal repeated
      measurement. CONCLUSIONS: The reliability and the dimensionality of a condition
      specific measure with high content validity for women having an abnormal cervical
      cancer screening results have been demonstrated. This new questionnaire called
      Consequences Of Screening in Cervical Cancer (COS-CC) covers in two parts the
      psychosocial experience in cervical cancer screening.

PMID- 30097014
TI  - EAPB: entropy-aware path-based metric for ontology quality.
AB  - BACKGROUND: Entropy has become increasingly popular in computer science and
      information theory because it can be used to measure the predictability and
      redundancy of knowledge bases, especially ontologies. However, current entropy
      applications that evaluate ontologies consider only single-point connectivity
      rather than path connectivity, and they assign equal weights to each entity and
      path. RESULTS: We propose an Entropy-Aware Path-Based (EAPB) metric for ontology
      quality by considering the path information between different vertices and
      textual information included in the path to calculate the connectivity path of
      the whole network and dynamic weights between different nodes. The information
      obtained from structure-based embedding and text-based embedding is multiplied by
      the connectivity matrix of the entropy computation. EAPB is analytically
      evaluated against the state-of-the-art criteria. We have performed empirical
      analysis on real-world medical ontologies and a synthetic ontology based on the
      following three aspects: ontology statistical information (data quantity),
      entropy evaluation (data quality), and a case study (ontology structure and text
      visualization). These aspects mutually demonstrate the reliability of the
      proposed metric. The experimental results show that the proposed EAPB can
      effectively evaluate ontologies, especially those in the medical informatics
      field. CONCLUSIONS: We leverage path information and textual information to
      enrich the network representational learning and aid in entropy computation. The
      analytics and assessments of semantic web can benefit from the structure
      information but also the text information. We believe that EAPB is helpful for
      managing ontology development and evaluation projects. Our results are
      reproducible and we will release the source code and ontology of this work after
      publication. (Source code and ontology:
      https://github.com/AnonymousResearcher1/ontologyEvaluate ).

PMID- 30097015
TI  - Knockdown of PAICS inhibits malignant proliferation of human breast cancer cell
      lines.
AB  - BACKGROUND: Phosphoribosylaminoimidazole carboxylase,
      phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS), an enzyme
      required for de novo purine biosynthesis, is associated with and involved in
      tumorigenesis. This study aimed to evaluate the role of PAICS in human breast
      cancer, which remains the most frequently diagnosed cancer and the leading cause
      of cancer-related death among women in less developed countries. RESULTS:
      Lentivirus-based short hairpin RNA targeting PAICS specifically depleted its
      endogenous expression in ZR-75-30 and MDA-MB-231 breast cancer cells. Depletion
      of PAICS led to a significant decrease in cell viability and proliferation. To
      ascertain the mechanisms through which PAICS modulates cell proliferation, flow
      cytometry was performed, and it was confirmed that G1-S transition was blocked in
      ZR-75-30 cells through PAICS knockdown. This might have occurred partly through
      the suppression of Cyclin E and the upregulation of Cyclin D1, P21, and CDK4.
      Moreover, PAICS knockdown obviously promoted cell apoptosis in ZR-75-30 cells
      through the activation of PARP and caspase 3 and downregulation of Bcl-2 and Bcl
      xl expression in ZR-75-30 cells. CONCLUSIONS: These findings demonstrate that
      PAICS plays an essential role in breast cancer proliferation in vitro, which
      provides a new opportunity for discovering and identifying novel effective
      treatment strategies.

PMID- 30097016
TI  - Correction to: STATAWAARS: a promoter motif associated with spatial expression in
      the major effector-producing tissues of the plantparasitic nematode
      Bursaphelenchus xylophilus.
AB  - Following publication of the original article [1], the authors reported that one
      of the authors' names was erroneously changed during proofing and published
      incorrectly. In this Correction the incorrect and correct author name are shown.
      The original publication of this article has been corrected.

PMID- 30097017
TI  - Characterization of the hot pepper (Capsicum frutescens) fruit ripening regulated
      by ethylene and ABA.
AB  - BACKGROUND: Ripening of fleshy fruits has been classically defined as climacteric
      or non-climacteric. Both types of ripening are controlled by plant hormones,
      notably by ethylene in climacteric ripening and by abscisic acid (ABA) in non
      climacteric ripening. In pepper (Capsicum), fruit ripening has been widely
      classified as non-climacteric, but the ripening of the hot pepper fruit appears
      to be climacteric. To date, how to regulate the hot pepper fruit ripening through
      ethylene and ABA remains unclear. RESULTS: Here, we examined ripening of the hot
      pepper (Capsicum frutescens) fruit during large green (LG), initial colouring
      (IC), brown (Br), and full red (FR) stages. We found a peak of ethylene emission
      at the IC stage, followed by a peak respiratory quotient at the Br stage. By
      contrast, ABA levels increased slowly before the Br stage, then increased sharply
      and reached a maximum level at the FR stage. Exogenous ethylene promoted
      colouration, but exogenous ABA did not. Unexpectedly, fluridone, an inhibitor of
      ABA biosynthesis, promoted colouration. RNA-sequencing data obtained from the
      four stages around ripening showed that ACO3 and NCED1/3 gene expression
      determined ethylene and ABA levels, respectively. Downregulation of ACO3 and
      NCED1/3 expression by virus-induced gene silencing (VIGS) inhibited and promoted
      colouration, respectively, as evidenced by changes in carotenoid, ABA, and
      ethylene levels, as well as carotenoid biosynthesis-related gene expression.
      Importantly, the retarded colouration in ACO3-VIGS fruits was rescued by
      exogenous ethylene. CONCLUSIONS: Ethylene positively regulates the hot pepper
      fruit colouration, while inhibition of ABA biosynthesis promotes colouration,
      suggesting a role of ABA in de-greening. Our findings provide new insights into
      processes of fleshy fruit ripening regulated by ABA and ethylene, focusing on
      ethylene in carotenoid biosynthesis and ABA in chlorophyll degradation.

PMID- 30097018
TI  - Repetitive somatic embryogenesis induced cytological and proteomic changes in
      embryogenic lines of Pseudotsuga menziesii [Mirb.].
AB  - BACKGROUND: To explore poorly understood differences between primary and
      subsequent somatic embryogenic lines of plants, we induced secondary (2ry) and
      tertiary (3ry) lines from cotyledonary somatic embryos (SEs) of two Douglas-fir
      genotypes: SD4 and TD17. The 2ry lines exhibited significantly higher embryogenic
      potential (SE yields) than the 1ry lines initiated from zygotic embryos (SD4,
      2155 vs 477; TD17, 240 vs 29 g- 1 f.w.). Moreover, we observed similar
      differences in yield between 2ry and 3ry lines of SD4 (2400 vs 3921 g- 1 f.w.).
      To elucidate reasons for differences in embryogenic potential induced by
      repetitive somatic embryogenesis we then compared 2ry vs 1ry and 2ry vs 3ry lines
      at histo-cytological (using LC-MS/MS) and proteomic levels. RESULTS: Repetitive
      somatic embryogenesis dramatically improved the proliferating lines' cellular
      organization (genotype SD4's most strongly). Frequencies of singulated, bipolar
      SEs and compact polyembryogenic centers with elongated suspensors and apparently
      cleavable embryonal heads increased in 2ry and (even more) 3ry lines. Among 2300
      2500 identified proteins, 162 and 228 were classified significantly
      differentially expressed between 2ry vs 1ry and 3ry vs 2ry lines, respectively,
      with special emphasis on "Proteolysis" and "Catabolic process" Gene Ontology
      categories. Strikingly, most of the significant proteins (> 70%) were down
      regulated in 2ry relative to 1ry lines, but up-regulated in 3ry relative to 2ry
      lines, revealing a down-up pattern of expression. GO category enrichment analyses
      highlighted the opposite adjustments of global protein patterns, particularly for
      processes involved in chitin catabolism, lignin and L-phenylalanine metabolism,
      phenylpropanoid biosynthesis, oxidation-reduction, and response to karrikin. Sub
      Network Enrichment Analyses highlighted interactions between significant proteins
      and both plant growth regulators and secondary metabolites after first
      (especially jasmonic acid, flavonoids) and second (especially salicylic acid,
      abscisic acid, lignin) embryogenesis cycles. Protein networks established after
      each induction affected the same "Plant development" and "Defense response"
      biological processes, but most strongly after the third cycle, which could
      explain the top embryogenic performance of 3ry lines. CONCLUSIONS: This first
      report of cellular and molecular changes after repetitive somatic embryogenesis
      in conifers shows that each cycle enhanced the structure and singularization of
      EMs through modulation of growth regulator pathways, thereby improving the lines'
      embryogenic status.

PMID- 30097019
TI  - The antibiotic peptaibol alamethicin from Trichoderma permeabilises Arabidopsis
      root apical meristem and epidermis but is antagonised by cellulase-induced
      resistance to alamethicin.
AB  - BACKGROUND: Trichoderma fungi live in the soil rhizosphere and are beneficial for
      plant growth and pathogen resistance. Several species and strains are currently
      used worldwide in co-cultivation with crops as a biocontrol alternative to
      chemical pesticides even though little is known about the exact mechanisms of the
      beneficial interaction. We earlier found alamethicin, a peptide antibiotic
      secreted by Trichoderma, to efficiently permeabilise cultured tobacco cells.
      However, pre-treatment with Trichoderma cellulase made the cells resistant to
      subsequent alamethicin, suggesting a potential mechanism for plant tolerance to
      Trichoderma, needed for mutualistic symbiosis. RESULTS: We here investigated
      intact sterile-grown Arabidopsis thaliana seedlings germinated in water or growth
      medium. These could be permeabilised by alamethicin but not if pretreated with
      cellulase. By following the fluorescence from the membrane-impermeable DNA
      binding probe propidium iodide, we found alamethicin to mainly permeabilise root
      tips, especially the apical meristem and epidermis cells, but not the root cap
      and basal meristem cells nor cortex cells. Alamethicin permeabilisation and
      cellulase-induced resistance were confirmed by developing a quantitative in situ
      assay based on NADP-isocitrate dehydrogenase accessibility. The combined assays
      also showed that hyperosmotic treatment after the cellulase pretreatment
      abolished the induced cellulase resistance. CONCLUSION: We here conclude the
      presence of cell-specific alamethicin permeabilisation, and cellulase-induced
      resistance to it, in root tip apical meristem and epidermis of the model organism
      A. thaliana. We suggest that contact between the plasma membrane and the cell
      wall is needed for the resistance to remain. Our results indicate a potential
      mode for the plant to avoid negative effects of alamethicin on plant growth and
      localises the point of potential damage and response. The results also open up
      for identification of plant genetic components essential for beneficial effects
      from Trichoderma on plants.

PMID- 30097020
TI  - Infection characteristics and treatment of Staphylococcus aureus bacteraemia at a
      tertiary children's hospital.
AB  - BACKGROUND: Staphylococcus aureus bacteraemia (SAB) causes considerable morbidity
      and mortality in children. Despite this, its epidemiology and risk factors are
      poorly understood, with minimal paediatric clinical trial data available to guide
      clinicians in management. We conducted a pilot study to characterise SAB and
      validate a severity classification for use in future clinical trials. METHODS:
      Patients with SAB were prospectively identified at Princess Margaret Hospital for
      Children (Perth, Western Australia) from May 2011 to December 2013. Retrospective
      data were collected from clinical and laboratory records. Cases were classified
      based on a priori defined criteria as simple (single or contiguous, peripheral
      site focus) or complex (multi-site, deep tissue, no focus or sepsis) and tested
      against risk factors and markers of severity of infection. RESULTS: There were 49
      cases of SAB (median age 7.7 years), with classification as simple (n = 30, 61%)
      and complex (n = 19, 39%) respectively. There were no deaths or relapses in our
      cohort. Only 10% of isolates were methicillin resistant S. aureus (MRSA), and
      none of these were healthcare-associated. Age, gender, Indigenous status, MRSA
      and healthcare-associated infections were not predictive of complex infection.
      Pre-existing malignancy was a risk factor for complex infection (p = 0.02).
      Complex infections were associated with a higher median maximum C reactive
      protein (216 mg/L vs 50 mg/L, p = < 0.001), longer median length of stay (42 vs
      10 days, p = < 0.001) and longer duration of antibiotic therapy (43 vs 34 days, p
      = 0.03). DISCUSSION: This is the first attempt to categorise paediatric SAB as
      simple versus complex, to guide clinicians in decision making. CONCLUSIONS: There
      is a wide spectrum of disease severity in paediatric SAB, with maximum CRP,
      length of stay, and duration of therapy greater in those with complex disease.
      Distinct cohorts with simple and complex courses which may be a target for future
      clinical trials have been described.

PMID- 30097021
TI  - Sense of community and willingness to support malaria intervention programme in
      urban poor Accra, Ghana.
AB  - BACKGROUND: The extensive research on community members' willingness to support
      malaria interventions ignores the role of psychosocial determinants. This study
      assesses the impact of individuals' sense of community (perceptions of community
      cohesion, altruism, seeking help from neighbours and migrant status) on their
      willingness to participate in a mosquito control programme using data on 768
      individuals from the 2013 RIPS Urban Health and Poverty Survey in poor coastal
      communities in Accra, Ghana. A contingent valuation experiment was employed to
      elicit individuals' willingness to support the programme by contributing nothing,
      labour time/money only or both. RESULTS: Findings show that different dimensions
      of sense of community related differently with willingness to support the
      programme. Perceived community cohesion was associated with lower odds while help
      seeking from neighbours and being a migrant were associated with higher odds of
      supporting the programme. Altruism was the only dimension not linked to
      willingness to participate. CONCLUSIONS: Different dimensions of sense of
      community are associated with community members' willingness to provide labour,
      time or both to support the malaria eradication programme. The findings of this
      study have implications for targeting social relational aspects, in addition to
      geographical aspects, of communities with malaria-resilient policy and
      intervention. They also warrant further research on psychosocial factors that
      predict willingness to support health programmes in urban poor settings.

PMID- 30097022
TI  - Systematic review of community participation interventions to improve maternal
      health outcomes in rural South Asia.
AB  - BACKGROUND: This is a systematic review on the effectiveness of community
      interventions in improving maternal health care outcomes in South Asia. METHODS:
      We searched electronic databases to June 2017. Randomised or cluster randomised
      studies in communities within rural/remote areas of Nepal, Bangladesh, India and
      Pakistan were included. Data were analysed as risk ratios (RR) or odds ratios
      (OR), and effects were adjusted for clustering. Meta-analyses were performed
      using random-effects and evidence quality was assessed. RESULTS: Eleven
      randomised trials were included from 5440 citations. Meta-analysis of all
      community interventions combined compared with control showed a small improvement
      in the number of women attending at least one antenatal care visit (RR 1.19, 95%
      CI 1.06 to 1.33). Two community mobilisation sub groups: home care using both
      male and female mobilisers, and education by community mobilisers, improved the
      number of women attending at least one antenatal visit. There was no difference
      in the number of women attending at least one antenatal visit for any other
      subgroup. There was no difference in the number of women attending 3 or more
      antenatal visits for all community interventions combined, or any community
      subgroup. Likewise, there was no difference in attendance at birth between all
      community interventions combined and control. Health care facility births were
      modestly increased in women's education groups (adjusted RR (1.15, 95% CI 1.11 to
      1.20; 2 studies)). Risk of maternal deaths after 2 years (RR 0.63, 95% CI 0.24 to
      1.64; 5 studies), and 3 years (RR 1.11, 95% CI 0.52 to 2.36; 2 studies), were no
      different between women's education groups and control. Community level
      mobilisation rather than health care messages at district level improved the
      numbers of women giving birth at health care facilities (RR1.09 (95%CI 1.06 to
      1.13; 1 study)). Maternal health care knowledge scores improved in two community
      based interventions, one involving education of male community members.
      CONCLUSION: Women's education interventions may improve the number of women
      seeking birth at a health care facility, but the evidence is of low quality. No
      impact on maternal mortality was observed Future research should explore the
      effectiveness of including male mobilisers. TRIAL REGISTRATION: This systematic
      review is registered with PROSPERO CRD42016033201 .

PMID- 30097023
TI  - Social relationships in adolescence and heavy episodic drinking from youth to
      midlife in Finland and Sweden - examining the role of individual, contextual and
      temporal factors.
AB  - BACKGROUND: Applying the Process-Person-Context-Time (PPCT) model of the
      bioecological theory, this study considers whether proximal processes between the
      individual and the microsystem (social relationships within family, peer group
      and school) during adolescence are associated with heavy episodic drinking (HED),
      from youth to midlife, and whether the macro level context (country) plays a role
      in these associations. METHODS: Participants of two prospective cohort studies
      from Finland and Sweden, recruited in 1983/1981 at age 16 (n = 2194/1080), were
      followed-up until their forties using postal questionnaires. Logistic regression
      analysis was used to examine associations between social relationships at age 16
      and HED (at least monthly intoxication or having six or more units of alcohol in
      one occasion) at ages 22/21, 32/30 and 42/43. Additive interactions between
      microsystem settings, as well as between settings and country, were also
      considered. RESULTS: Consistent with the PPCT model, we found individual,
      contextual and temporal aspects to be associated with drinking habits. Higher
      levels of poor family relationships were associated with an increased likelihood
      of HED (ages 22/21 and 32/30) in both Finnish women and men and Swedish men.
      Higher levels of peer contact were associated with an increased likelihood of HED
      in both Finnish women (ages 32 and 42) and men (ages 22 and 32), and Swedish men
      (age 21). In contrast with the other groups, poorer relationships with classmates
      were associated with an increased likelihood of HED (age 30) for Swedish women
      only. For women, the combined effect of having both daily peer contact and living
      in Finland for HED at age 42/43 was statistically distinguishable from a pure
      additive effect. CONCLUSIONS: Micro and to a lesser extent macro level contexts
      are associated with heavy episodic drinking well into adulthood. The most
      relevant processes in the adolescent microsystem occur in family and peer
      settings. However, long-lasting protective or risk-raising effects between
      different settings and later HED were not found. Promoting good relationships
      across different contexts during adolescence may reduce the incidence of HED in
      adulthood.

PMID- 30097024
TI  - Combination of PCT, sNFI and dCHC for the diagnosis of ascites infection in
      cirrhotic patients.
AB  - BACKGROUND: It is difficult to diagnose ascites infection early in cirrhotic
      patients. The present study was to create and evaluate a new bioscore combined
      with PCT, sNFI and dCHC in the diagnosis of ascites infection in cirrhotic
      patients. METHODS: Two hundred and fifty-nine consecutive patients were enrolled;
      of which 51 patients were culture-positive spontaneous bacterial peritonitis
      (culture-positive SBP) and 58 patients were culture-negative SBP. The efficacy of
      procalcitonin(PCT), c-reactive protein (CRP), white blood cell (WBC), mean
      fluorescence intensity of mature neutrophils(sNFI) and difference in hemoglobin
      concentration between newly formed and mature red blood cells(dCHC) for
      diagnosing ascites infection was examined. These parameters were used to create a
      scoring system. The scoring system was analyzed by logistic regression analysis
      to determine which parameters were statistically different between ascites
      infection and non-ascites infection patients. Receiver operating characteristic
      curve (ROC) was used to analyze the diagnostic ability of bioscore for ascites
      infection. RESULTS: In ROC analysis, the area under the curves (AUC) for PCT was
      0.852 (95% CI 0.803-0.921, P < 0.001), dCHC 0.837 (95% CI 0.773-0.923, P <
      0.001), CRP 0.669 (95% CI 0.610-0.732, P = 0.0624), sNFI 0.838 (95% CI 0.777
      0.903, P < 0.001), and WBC 0.624 (95% CI 0.500-0.722, P = 0.0881). Multivariate
      analysis revealed PCT, dCHC and sNFI to be statistically significant. The
      combination of these three parameters in the bioscore had an AUC of 0.937 (95% CI
      0.901-0.994, P < 0.001). A bioscore of >=3.40 was considered to be statistically
      significant in making a positive diagnosis of ascites infection. In different
      groups of ascites infection, bioscore also shown a high diagnostic value of AUC
      was 0.947(95% CI 0.882-0.988, P < 0.001) and 0.929 (95% CI 0.869-0.974, P <
      0.001) for culture-positive SBP and culture-negative SBP group respectively.
      CONCLUSION: The composite markers of combining PCT, dCHC and sNFI could be a
      valuable diagnostic score to early diagnose ascites infection in patients with
      cirrhosis.

PMID- 30097025
TI  - Persistent detection of Zika virus RNA from an infant with severe microcephaly -
      a case report.
AB  - BACKGROUND: Zika virus (ZIKV) is a recently emerged arbovirus, which infection
      during pregnancy is associated with a series of congenital malformations,
      collectively denominated Congenital Zika Syndrome (CZS). Following infection,
      ZIKV RNA has a median duration period of 10 days in plasma and up to 6 months in
      semen in immunocompetent adult individuals. Moreover, ZIKV is able to replicate
      and persist in fetal brains and placentas, consequently, infection is associated
      with pregnancy loss, albeit the pathogenic mechanisms are still unknown. CASE
      PRESENTATION: Here we report a CZS case of an infant born during the ZIKV
      outbreak in northeast Brazil, the child presented recurrent episodes of seizures
      with prolonged presence of ZIKV RNA on the central nervous system (CNS) and
      blood. ZIKV RNA was identified and partially sequenced from a sample of
      cerebrospinal fluid (CSF) obtained from the infant with 6 months of life, and
      later from another sample after the infant completed 17 months of life. Commonly
      congenital infections were discarded based on STORCH (syphilis, toxoplasmosis,
      rubella, cytomegalovirus and herpes simplex virus) negative laboratory results.
      Presence of specific ZIKV antibodies on both mother and children confirmed the
      association of severe microcephaly and ZIKV infection, diagnosed after birth.
      CONCLUSIONS: Altogether, our data raise the possibility that CZS cases may result
      in prolonged viral presence, these findings could be useful for therapy and
      diagnostic recommendations.

PMID- 30097027
TI  - Correction to: Identifying common barriers and facilitators to linkage and
      retention in chronic disease care in western Kenya.
AB  - After the publication of the original article [1], it was highlighted that Fig. 1
      was incorrectly labeled.

PMID- 30097026
TI  - Vaccination demonstration zone successfully controls rabies in Guangxi Province,
      China.
AB  - BACKGROUND: Guangxi is the province most seriously affected by rabies virus
      (RABV) in China. Those most affected by RABV each year are people in rural areas,
      where dogs are the main cause of human infection with the virus. METHODS: In this
      study, we established a rabies vaccination demonstration program that included
      eradication, core, and peripheral areas. This program was implemented for 9 years
      and comprised three stages: 12 counties in the first stage (2008-2010), 21
      counties in the second stage (2011-2013), and then extending to all counties of
      Guangxi Province in the third stage (2014-2016). The program included a dog
      vaccination campaign, surveillance of clinically healthy dogs who may be
      potential RABV carriers, monitoring anti-RABV antibody titers in vaccinated dogs,
      and compiling and reporting statistics of human rabies cases. RESULTS: The target
      effectiveness was achieved in the eradication, core, and peripheral areas in all
      three stages. The vaccination demonstration program successfully promoted RABV
      vaccination of domestic dogs throughout Guangxi Province by drawing upon the
      experience gained at key points. Compared with a vaccination coverage rate of
      39.42-46.85% in Guangxi Province overall during 2003-2007, this rate gradually
      increased to 48.98-52.67% in 2008-2010, 60.24-69.67% in 2011-2013, and 70.09
      71.53% in 2014-2016, thereby meeting World Health Organization requirements. The
      total cases of human rabies in the province decreased from 602 in 2004 to 41
      cases in 2017. CONCLUSIONS: The present pilot vaccination program obviously
      increased the rabies vaccination and seroconversion rates, and effectively
      reduced the spread of rabies from dogs to humans as well as the number of human
      rabies cases, thus successfully controlling rabies in Guangxi.

PMID- 30097028
TI  - Understanding health systems to improve community and facility level newborn care
      among displaced populations in South Sudan: a mixed methods case study.
AB  - BACKGROUND: Targeted clinical interventions have been associated with a decreased
      risk of neonatal morbidity and mortality. In conflict-affected countries such as
      South Sudan, however, implementation of lifesaving interventions face barriers
      and facilitators that are not well understood. We aimed to describe the factors
      that influence implementation of a package of facility- and community-based
      neonatal interventions in four displaced person camps in South Sudan using a
      health systems framework. METHODS: We used a mixed method case study design to
      document the implementation of neonatal interventions from June to November 2016
      in one hospital, four primary health facilities, and four community health
      programs operated by International Medical Corps. We collected primary data using
      focus group discussions among health workers, in-depth interviews among program
      managers, and observations of health facility readiness. Secondary data were
      gathered from documents that were associated with the implementation of the
      intervention during our study period. RESULTS: Key bottlenecks for implementing
      interventions in our study sites were leadership and governance for comprehensive
      neonatal services, health workforce for skilled care, and service delivery for
      small and sick newborns. Program managers felt national policies failed to
      promote integration of key newborn interventions in donor funding and clinical
      training institutions, resulting in deprioritizing newborn health during
      humanitarian response. Participants confirmed that severe shortage of skilled
      care at birth was the main bottleneck for implementing quality newborn care.
      Solutions to this included authorizing the task-shifting of emergency newborn
      care to mid-level cadre, transitioning facility-based traditional birth
      attendants to community health workers, and scaling up institutions to upgrade
      community midwives into professional midwives. Additionally, ongoing supportive
      supervision, educational materials, and community acceptance of practices enabled
      community health workers to identify and refer small and sick newborns.
      CONCLUSIONS: Improving integration of newborn interventions into national
      policies, training institutions, health referral systems, and humanitarian supply
      chain can expand emergency care provided to women and their newborns in these
      contexts.

PMID- 30097029
TI  - Irinotecan-platinum combination therapy for previously untreated extensive-stage
      small cell lung cancer patients: a meta-analysis.
AB  - BACKGROUND: There is still a debate regarding whether regimens combining
      irinotecan with platinum could replace regimens combining etoposide with
      platinum, as first-line chemotherapy for extensive-stage small cell lung cancer
      (ES-SCLC). We performed a meta-analysis to compare these regimens as first-line
      chemotherapy for ES-SCLC. METHODS: A literature search for randomized controlled
      trials was performed using the Cochrane Library, PubMed, and Embase. The inverse
      variance method was used to estimate summary hazard ratios and their 95%
      confidence intervals for overall survival and progression free survival. Relative
      risk was used to estimate the overall response rate, disease control rate, 1-year
      survival, 2-year survival, and adverse event data. RESULT: Nine randomized
      controlled trials (2451 patients) were included. Regimens combining irinotecan
      and platinum improved overall survival, progression-free survival and overall
      response rate compared to combination etoposide and platinum regimens. Meanwhile,
      superior progression-free survival and overall response rate outcomes were
      observed in the Asian subgroup of patients. These patients receiving a
      combination irinotecan and platinum regimen experienced grade 3-4 diarrhea more
      frequently and experienced less hematologic toxic events than the non-Asian
      groups. CONCLUSIONS: Our data suggest that a combination irinotecan and platinum
      regimen can prolong overall survival, progression-free survival and overall
      response rate for patients with ES-SCLC as compared to a combination etoposide
      and platinum regimen. And the Asian patients could benefit from irinotecan
      combined with platinum easier.

PMID- 30097030
TI  - Mycetoma: a clinical dilemma in resource limited settings.
AB  - BACKGROUND: Mycetoma is a chronic mutilating disease of the skin and the
      underlying tissues caused by fungi or bacteria. Although recently included in the
      list of neglected tropical diseases by the World Health Organization, strategic
      control and preventive measures are yet to be outlined. Thus, it continues to
      pose huge public health threat in many tropical and sub-tropical countries. If
      not detected and managed early, it results into gruesome deformity of the limbs.
      Its low report and lack of familiarity may predispose patients to misdiagnosis
      and delayed treatment initiation. More so in situation where diagnostic tools are
      limited or unavailable, little or no option is left but to clinically diagnose
      these patients. Therefore, an overview of clinical course of mycetoma, a
      suggested diagnostic algorithm and proposed use of materials that cover the
      exposed susceptible parts of the body during labour may assist in the prevention
      and improvement of its management. Furthermore, early reporting which should be
      encouraged through formal and informal education and sensitization is strongly
      suggested. MAIN TEXT: An overview of the clinical presentation of mycetoma in the
      early and late phases, clues to distinguish eumycetoma from actinomycetoma in the
      field and the laboratory, differential diagnosis and a suggested diagnostic
      algorithm that may be useful in making diagnosis amidst the differential
      diagnosis of mycetoma is given. Additionally, a proposed preventive measures
      which may be helpful in the community is also provided. Since treatment is
      currently based on expert opinion, we encourage active research to establish
      treatment guideline for it. CONCLUSION: Since delay in visiting health facility
      results into gruesome complication, early presentation, recognition and
      initiation of appropriate choice of regimen is helpful in reducing complications.
      The clinical overview of mycetoma and the suggested algorithm may enhance
      suspicion and possibly increase recognition of mycetoma in the community and
      further guide in differentiation of eumycetoma from actinomycetoma. There is an
      urgent need for research funding for mycetoma, a disease plagued by severe
      physical disabilities and social stigma leading to isolation.

PMID- 30097031
TI  - The portfolio effect cushions mosquito populations and malaria transmission
      against vector control interventions.
AB  - BACKGROUND: Portfolio effects were first described as a basis for mitigating
      against financial risk by diversifying investments. Distributing investment
      across several different assets can stabilize returns and reduce risks by
      statistical averaging of individual asset dynamics that often correlate weakly or
      negatively with each other. The same simple probability theory is equally
      applicable to complex ecosystems, in which biological and environmental diversity
      stabilizes ecosystems against natural and human-mediated perturbations. Given the
      fundamental limitations to how well the full complexity of ecosystem dynamics can
      be understood or anticipated, the portfolio effect concept provides a simple
      framework for more critical data interpretation and pro-active conservation
      management. Applied to conservation ecology purposes, the portfolio effect
      concept informs management strategies emphasizing identification and maintenance
      of key ecological processes that generate complexity, diversity and resilience
      against inevitable, often unpredictable perturbations. IMPLICATIONS: Applied to
      the reciprocal goal of eliminating the least valued elements of global
      biodiversity, specifically lethal malaria parasites and their vector mosquitoes,
      simply understanding the portfolio effect concept informs more cautious
      interpretation of surveillance data and simulation model predictions. Malaria
      transmission mediated by guilds of multiple vectors in complex landscapes, with
      highly variable climatic and meteorological conditions, as well as changing
      patterns of land use and other human behaviours, will systematically tend to be
      more resilient to attack with vector control than it appears based on even the
      highest quality surveillance data or predictive models. CONCLUSION: Malaria
      vector control programmes may need to be more ambitious, interpret their short-to
      medium term assessments of intervention impact more cautiously, and manage
      stakeholder expectations more conservatively than has often been the case thus
      far.

PMID- 30097033
TI  - Survival after repeated surgery for lung cancer with idiopathic pulmonary
      fibrosis: a retrospective study.
AB  - BACKGROUND: Patients with idiopathic pulmonary fibrosis (IPF) have a high risk of
      developing lung cancer, but few studies have investigated the long-term outcomes
      of repeated surgery in such patients. The purpose of this study was to evaluate
      the surgical outcomes of repeated lung cancer surgery in patients with IPF.
      METHODS: From January 2001 to December 2015, 108 lung cancer patients with IPF
      underwent pulmonary resection at two institutions; 13 of these patients underwent
      repeated surgery for lung cancer, and their data were reviewed. RESULTS: The
      initial procedures of the 13 patients were lobectomy in 8, segmentectomy in 2,
      and wedge resection in 3. The subsequent procedures were wedge resection in 10
      and segmentectomy in 3. The clinical stage of the second tumor was stage IA in 12
      and stage IB in 1. Postoperatively, 3 patients (23.1%) developed acute
      exacerbation (AE) of IPF and died. The rate of decrease in percent vital capacity
      was significantly higher in patients with AE than in those without AE (p =
      0.011). The 3-year overall survival rate was 34.6%. The causes of death were
      cancer-related in 7, AE of IPF in 3, and metachronous lung cancer in 1.
      CONCLUSIONS: Despite limited resection, a high incidence of AE was identified.
      The early and long-term outcomes of repeated surgery in lung cancer patients with
      IPF were poor because of the high risk of AE of IPF and lung cancer recurrence.
      Long-term intensive surveillance will be required to determine whether surgical
      intervention is justified in patients with multiple primary lung cancers and IPF.

PMID- 30097034
TI  - "I aspire to look and feel healthy like the posts convey": engagement with
      fitness inspiration on social media and perceptions of its influence on health
      and wellbeing.
AB  - BACKGROUND: Fitspiration is a popular social media trend containing images,
      quotes and advice related to exercise and healthy eating. This study aimed to 1)
      describe the types of fitspiration content that users access and how they engage
      with content, 2) investigate the disordered eating and exercise behaviours and
      psychological distress of individuals who access fitspiration, and 3) understand
      the perceived influence of fitspiration on health and wellbeing. METHODS:
      Participants who access fitspiration content were recruited via social media to
      complete a cross-sectional online survey. Participants' psychological distress
      was measured using the Kessler 10 Psychological Distress Scale (K10); disordered
      eating behaviours using the Eating Attitudes Test-26 (EAT-26); and compulsive
      exercise behaviours using the Exercise Addiction Inventory (EAI). Participants
      also answered a series of open-ended questions about their experiences with
      fitspiration. A descriptive statistical analysis was conducted for quantitative
      data. Responses to open-ended questions were analysed for key themes using an
      iterative process of open, axial and thematic coding. RESULTS: Participants (N =
      180, 151 female, median age 23.0 years (IQR 19.0, 28.5)) most commonly accessed
      content posted by personal trainers and athletes (59.4%), posts tagged with the
      'fitspiration' hashtag (53.9%) and posted by 'everyday' people (53.3%). Overall,
      17.7% of participants were classified as high risk for an eating disorder, 17.4%
      reported very high levels of psychological distress, and 10.3% were at risk of
      addictive exercise behaviours. Participants described both positive and negative
      influences of engaging with fitspiration content. The influence on their health
      beliefs and behaviours was explained through four key themes: 1) Setting the
      'healthy ideal', 2) Failure to achieve the 'ideal', 3) Being part of a community,
      and 4) Access to reliable health information. CONCLUSIONS: Many participants
      reported benefits of fitspiration content including increased social support and
      access to health information. However, participants also reported that
      fitspiration content could negatively influence their wellbeing and perception of
      healthy goals. Content posted by relatable individuals or qualified experts was
      perceived as most trustworthy. Future research is needed to determine the
      individual and content-related factors associated with negative and positive
      fitspiration experiences.

PMID- 30097035
TI  - Pure PBL, Hybrid PBL and Lecturing: which one is more effective in developing
      cognitive skills of undergraduate students in pediatric nursing course?
AB  - BACKGROUND: Nursing education in Iran has conventionally focused on lecture-based
      strategies. Improvements in teaching and learning over the years have led to an
      expansion of the pedagogies available to educators. Likewise, there has been a
      suggestion for a move toward more learner-centered teaching strategies and
      pedagogies that can result in improvement in learning. This study was undertaken
      to investigate the effects of Problem-Based Learning in developing cognitive
      skills in learning Pediatric Nursing among university students. METHODS: In this
      quasi-experimental, posttest-only nonequivalent control group design, the
      subjects were undergraduate students who had enrolled in Pediatric Nursing II at
      Islamic Azad University in Iran. The experiment was conducted over a period of
      eight weeks, one two-hour session and two two-hour sessions. Two experimental
      groups, Pure Problem-Based Learning (PPBL) and the Hybrid Problem- Based Learning
      (HPBL), and one Lecturing or Conventional Teaching and Learning (COTL) group were
      involved. In the PPBL group, PBL method with guided questions and a tutor, and in
      the HPBL group, problem-based learning method, some guided questions, minimal
      lecturing and a tutor were used. The COTL group, however, underwent learning
      using conventional instruction utilizing full lecture. The three groups were
      compared on cognitive performances, namely, test performance, mental effort, and
      instructional efficiency. Two instruments, i.e., Pediatric Nursing Performance
      Test (PNPT) and Paas Mental Effort Rating Scale (PMER) were used. In addition,
      the two-Dimensional Instructional Efficiency Index (IEI) formula was utilized.
      The statistical analyses used were ANOVA, ANCOVA, and mixed between-within
      subjects ANOVA. RESULTS: Results showed that the PPBL and HPBL instructional
      methods, in comparison with COTL, enhanced the students' overall and higher-order
      performances in Pediatric Nursing, and induced higher level of instructional
      efficiency with less mental effort (p < 0.005). Although there was no significant
      difference in lower-order performance among the groups during the posttest (p =
      0.92), the HPBL group outperformed the COTL group on the delayed posttest (p =
      0.028). CONCLUSIONS: It may be concluded that both forms of PBL were effective
      for learning Pediatric Nursing. Moreover, PBL appears to be useful where there
      are shortages of instructors for handling teaching purposes.

PMID- 30097036
TI  - Development, implementation and evaluation of Australia's first national
      continuing medical education program for the timely diagnosis and management of
      dementia in general practice.
AB  - BACKGROUND: Dementia is the second leading cause of death in Australia. Over half
      of patients with dementia are undiagnosed in primary care. This paper describes
      the development, implementation and initial evaluation of the first national
      continuing medical education program on the timely diagnosis and management of
      dementia in general practice in Australia. METHODS: Continuing medical education
      workshops were developed and run in 16 urban and rural locations across Australia
      (12 were delivered as small group workshops, four as large groups), and via
      online modules. Two train-the-trainer workshops were held. The target audience
      was general practitioners, however, international medical graduates, GP
      registrars, other doctors, primary care nurses and other health professionals
      were also welcome. Self-complete questionnaires were used for the evaluation.
      RESULTS: Of 1236 people (GPs, other doctors, nurses and other health
      professionals) who participated in the program, 609 completed the full program
      (small group workshops (282), large group workshops (75), online modules (252));
      and 627 elected to undertake one or more individual submodules (large group
      workshops (444), online program (183)). Of those who completed the full program
      as a small group workshop, 14 undertook the additional Train-the-trainer program.
      76% of participants felt that their learning needs were entirely met and 78% felt
      the program was entirely relevant to their practice. CONCLUSION: Continuing
      medical education programs are an effective method to deliver education to GPs. A
      combination of face-to-face and online delivery modes increases reach to primary
      care providers. Train-the-trainer sessions and online continuing medical
      education programs promote long-term delivery sustainability. Further research is
      required to determine the long-term knowledge translation effects of the program.

PMID- 30097037
TI  - Travel to farms in the lowlands and inadequate malaria information significantly
      predict malaria in villages around Lake Tana, northwest Ethiopia: a matched case
      control study.
AB  - BACKGROUND: In Ethiopia, malaria has declined in the last decade; only a small
      number of cases have been reported, primarily from hotspots. The contribution of
      house proximity to water bodies and the role of migration in malaria transmission
      has not yet been examined in detail in northwest Ethiopia. Individual and
      household-level environmental and socio-demographic drivers of malaria
      heterogeneity were explored contextually in meso-endemic villages around Lake
      Tana, northwest Ethiopia. METHODS: A health facility-based paired age-sex matched
      case-control study involving 303 matched pairs was undertaken from 10 October
      2016, to 30 June 2017. Geo-referencing of case households, control households,
      proximate water bodies, and health centres was carried out. A pretested and
      structured questionnaire was used to collect data on socio-demography, household
      assets, housing, travel history, and malaria intervention measures. Medians
      (interquartile range) were computed for continuous variables. Pearson's Chi
      square/Fisher's exact test was used to detect significant differences in
      proportions. Principal component analysis was performed to estimate household
      wealth. Stratified analysis was used to confirm confounding and interaction. A
      multivariable conditional logistic regression model was used to detect risk
      factors for malaria. RESULTS: Of 303 malaria cases, 59 (19.5% [15.4-24.3]) were
      imported malaria cases whereas 244 (80.5% [75.7-84.6]) were locally acquired
      malaria cases. In bivariate analysis, marital status, educational status, and bed
      net ownership were significantly associated with malaria cases. In multivariable
      adjustment, travel to malarious lowlands in the preceding month (adjusted mOR =
      7.32; 95% CI 2.40-22.34), household member's travel to malarious lowlands
      (adjusted mOR = 2.75; 95% CI 1.02-7.44), and inadequate health information on
      malaria (adjusted mOR = 1.57; 95% CI 1.03-2.41) were predictors of malaria.
      Stratified analysis confirmed that elevation of households and travel to
      malarious lowlands were not effect modifiers. Travel to malarious lowlands had a
      confounding effect on malaria but elevation of households did not. CONCLUSIONS:
      In this study, travel to farms in the lowlands and inadequate health information
      on malaria were risk factors for malaria in villages around Lake Tana. This
      evidence is critical for the design of improved strategic interventions that
      consider imported malaria cases and approaches for accessing health information
      on malaria control in northwest Ethiopia.

PMID- 30097032
TI  - Natural product derivative Gossypolone inhibits Musashi family of RNA-binding
      proteins.
AB  - BACKGROUND: The Musashi (MSI) family of RNA-binding proteins is best known for
      the role in post-transcriptional regulation of target mRNAs. Elevated MSI1 levels
      in a variety of human cancer are associated with up-regulation of Notch/Wnt
      signaling. MSI1 binds to and negatively regulates translation of Numb and APC
      (adenomatous polyposis coli), negative regulators of Notch and Wnt signaling
      respectively. METHODS: Previously, we have shown that the natural product (-)
      gossypol as the first known small molecule inhibitor of MSI1 that down-regulates
      Notch/Wnt signaling and inhibits tumor xenograft growth in vivo. Using a
      fluorescence polarization (FP) competition assay, we identified gossypolone (Gn)
      with a > 20-fold increase in Ki value compared to (-)-gossypol. We validated Gn
      binding to MSI1 using surface plasmon resonance, nuclear magnetic resonance, and
      cellular thermal shift assay, and tested the effects of Gn on colon cancer cells
      and colon cancer DLD-1 xenografts in nude mice. RESULTS: In colon cancer cells,
      Gn reduced Notch/Wnt signaling and induced apoptosis. Compared to (-)-gossypol,
      the same concentration of Gn is less active in all the cell assays tested. To
      increase Gn bioavailability, we used PEGylated liposomes in our in vivo studies.
      Gn-lip via tail vein injection inhibited the growth of human colon cancer DLD-1
      xenografts in nude mice, as compared to the untreated control (P < 0.01, n = 10).
      CONCLUSION: Our data suggest that PEGylation improved the bioavailability of Gn
      as well as achieved tumor-targeted delivery and controlled release of Gn, which
      enhanced its overall biocompatibility and drug efficacy in vivo. This provides
      proof of concept for the development of Gn-lip as a molecular therapy for colon
      cancer with MSI1/MSI2 overexpression.

PMID- 30097039
TI  - High genetic carrier frequency of Wilson's disease in France: discrepancies with
      clinical prevalence.
AB  - BACKGROUND: Wilson's disease (WD) is a rare autosomal recessive metabolic disease
      caused by ATP7B gene mutations tat cause excessively high copper levels,
      particularly in the liver and brain. The WD phenotype varies in terms of its
      clinical presentation and intensity. Diagnosing this metabolic disorder is
      important as a lifelong treatment, based on the use of copper chelating agents or
      zinc salts, is more effective if it's started early. Worldwide prevalence of WD
      is variable, with an average of 1/30,000. In France, a recent study based on
      French health insurance data estimated the clinical prevalence of the disease to
      be around 3/200,000. METHODS: To estimate the genetic prevalence of WD in France,
      we analysed the ATP7B gene by Next Generation Sequencing from a large French
      cohort of indiscriminate subjects. RESULTS: We observed a high heterozygous
      carrier frequency of ATP7B in France. Among the 697 subjects studied, 18 variants
      classified as pathogenic or probably pathogenic were found at heterozygous level
      in 22 subjects (22 alleles/1394 alleles), yielding a prevalence of 0.032 or 1/31
      subjects. CONCLUSIONS: This considerable and unexplained discrepancy between the
      heterozygous carrier frequency and the clinical prevalence of WD may be explained
      by the clinical variability, the incomplete penetrance and the existence of
      modifiers genes. It suggests that the molecular analysis of ATP7B should be
      interpreted with caution, always alongside copper assays (ceruloplasmin, relative
      exchangeable copper, 24 h-urinary copper excretion) with particular respect to
      exome sequencing.

PMID- 30097038
TI  - Renal hypouricemia caused by novel compound heterozygous mutations in the
      SLC22A12 gene: a case report with literature review.
AB  - BACKGROUND: Renal hypouricemia (RHUC) is a heterogeneous genetic disorder that is
      characterized by decreased serum uric acid concentration and increased fractional
      excretion of uric acid. Previous reports have revealed many functional mutations
      in two urate transporter genes, SLC22A12 and/or SLC2A9, to be the causative
      genetic factors of this disorder. However, there are still unresolved patients,
      suggesting the existence of other causal genes or new mutations. Here, we report
      an RHUC patient with novel compound heterozygous mutations in the SLC22A12 gene.
      CASE PRESENTATION: A 27-year-old female presenting with recurrent hypouricemia
      during routine checkups was referred to our hospital. After obtaining the
      patient's consent, both the patient and her healthy parents were analyzed using
      whole-exome sequencing (WES) and Sanger sequencing to discover and validate
      causal mutations, respectively. The prioritization protocol of WES screened out
      two mutations of c.269G > A/p.R90H and c.1289_1290insGG/p.M430fsX466, which are
      both located in the SLC22A12 gene, in the patient. Sanger sequencing further
      confirmed that the patient's heterozygous c.269G > A/p.R90H mutation, which has
      been reported previously, derived from her mother, and the heterozygous
      c.1289_1290insGG/p.M430fsX466 mutation, which was found for the first time,
      derived from her father. p.R90H, which is highly conserved among different
      species, may decrease the stability of this domain and was considered to be
      almost damaging in silicon analysis. p.M430fsX466 lacks the last three
      transmembrane domains, including the tripeptide motif (S/T)XPhi (X = any amino
      acid and Phi = hydrophobic residue), at the C-terminal, which interact with
      scaffolding protein PDZK1 and thus will possibly lead to weak functioning of
      urate transport through the disruption of the "transporter complex" that is
      formed by URAT1 and PDZK1. CONCLUSIONS: We report a Chinese patient with RHUC,
      which was caused by compound heterozygous mutations of the SLC22A12 gene, using
      WES and Sanger sequencing for the first time. Mutation-induced structural
      instability or malfunction of the urate transporter complex may be the main
      mechanisms for this hereditary disorder.

PMID- 30097040
TI  - The quality of life of Croatian women after mastectomy: a cross-sectional single
      center study.
AB  - BACKGROUND: Measuring the quality of life (QoL) of women with breast cancer is an
      important aspect of measuring treatment success. In Croatia, no QoL studies have
      been carried out with a focus on patients after mastectomy. The aim of this study
      was to examine QoL 1 month and 1 year after mastectomy. METHODS: This cross
      sectional single-center study of quality of life was conducted in 101 patients,
      50 of whom had undergone a mastectomy 1 month prior, and 51 of whom had undergone
      a mastectomy 1 year prior. The study was conducted from July 2015 to June 2016.
      The questionnaires used in the study were developed by the European Organisation
      for Research and Treatment of Cancer (EORTC). The questionnaire EORTC QLQ-C30
      assesses the QoL of cancer patients, and the questionnaire EORTC QLQ-BR23 is a
      disease-specific breast cancer module. A chi square test, Fisher's exact test,
      Kolmogorov-Smirnov test, Student's t-test and Mann-Whitney U test were performed
      in the statistical analysis using the statistical program SPSS (Inc. Released
      2008. SPSS Statistics for Windows, Version 17.0. Chicago: SPSS Inc.). RESULTS:
      Patients who had undergone a mastectomy a year earlier placed a higher value on
      their health state than did those who had undergone a mastectomy a month earlier.
      The most affected values of functional status on the EORTC QLQ-C30 scale were
      emotional functioning (37.5 [95% CI 33.3-61.6]) and sexual functioning (16.67
      [95% CI 0-33.3]) 1 month and 1 year after mastectomy, respectively. The most
      affected symptoms on the EORTC QLQ-C30 scale were hair loss 66.67 [95% CI 33.3
      100]) and fatigue 33.33 [95% CI 24-44]) 1 month and 1 year after mastectomy,
      respectively. CONCLUSION: In our study, both functional and symptom scales were
      more affected in women 1 month after mastectomy. QoL was considerably improved in
      women 1 year after the surgery compared to 1 month after mastectomy. The results
      of this study could contribute to the public awareness of the QoL of breast
      cancer patients.

PMID- 30097041
TI  - Future risk of metabolic syndrome in women with a previous LGA delivery
      stratified by gestational glucose tolerance: a prospective cohort study.
AB  - BACKGROUND: Whether the delivery of a large-for-gestational-age (LGA) infant
      predicts future maternal metabolic syndrome (MetS) is not known. To this aim, we
      investigated the incidence of MetS and its components in women with or without a
      history of gestational diabetes mellitus (GDM) with a view to the birth weight of
      the offspring. METHODS: Eight hundred seventy six women treated for their
      pregnancies in Kuopio University Hospital in 1989-2009 underwent a follow-up
      study (mean follow-up time 7.3 (SD 5.1) years), of whom 489 women with GDM and
      385 normoglycemic controls. The women were stratified into two groups according
      to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational
      age; AGA) (n = 662) and > 90th percentile (LGA) (n = 116). MetS and its
      components were evaluated in the follow-up study according to the International
      Diabetes Federation criteria. RESULTS: LGA vs. AGA delivery was associated with a
      higher incidence of MetS at follow-up in women with a background of GDM (54.4%
      vs. 43.6%), but not in women without GDM. CONCLUSION: An LGA delivery in women
      with GDM is associated with a higher risk of future MetS and this group is
      optimal to study preventive measures for MetS. In contrast, an LGA delivery after
      a normoglycemic pregnancy was not associated with an increased future maternal
      MetS risk.

PMID- 30097042
TI  - Phytochemical analysis and evaluation of the cytotoxic, antimicrobial and
      antioxidant activities of essential oils from three Plectranthus species grown in
      Saudi Arabia.
AB  - BACKGROUND: Cancers and microbial infections are still a major health problem,
      therefore research on new anticancer and antimicrobial agents ought to be
      continued. Natural products including essential oils from medicinal plants
      continue to be an important resource to manage various diseases. Thus, the
      particular objectives of this study are to investigate the chemical composition,
      cytotoxic, antimicrobial and antioxidant activities of three Plectranthus species
      namely P. cylindraceus Hocst. ex Benth., P. asirensis JRI Wood and P. barbatus
      Andrews grown in Saudi Arabia. METHODS: The essential oils of the three
      Plectranthus species were obtained by hydrodistllation and analyzed using GC/FID
      and GC-MS. The essential oils were further assessed for their cytotoxic,
      antimicrobial and antioxidant activities. Determination of the cytotoxic activity
      was carried out against Hela, HepG2 and HT-29 cancer cell lines by utilizing MTT
      assay. The antimicrobial activity was assessed against six bacterial and fungal
      strains by using broth micro-dilution assay. In addition, the antioxidant
      activity was evaluated utilizing the DPPH and beta-Carotene-linoleic acid assays.
      RESULTS: The GC/FID and GC-MS analysis led to the identification of 59, 60 and 42
      compounds representing 89.0% 95.0 and 97.1% of the total essential oils of P.
      cylindraceus, P. asirensis and P. barbatus, respectively. The essential oils were
      characterized by a high content of oxygenated sesquiterpenes in P. cylindraceus,
      sesquiterpene hydrocarbons in P. asirensis and monoterpene hydrocarbons in P.
      barbatus where maaliol (42.8%), beta-caryophyllene (13.3%) and alpha-pinene,
      (46.2%) were the predominant compounds. Additionally, the oils particularly of P.
      cylindraceus and P. barbatus exhibited remarkable cytotoxic and antimicrobial
      activities with IC50-values between 3.8 and 7.5 MUg/mL and MIC-values ranging
      from 0.137 to 4.40 mg/mL. Moreover, the oils showed moderate to high radical
      scavenging and antioxidative activities ranging from 52 to 75% at the highest
      concentration of 1 mg/mL. CONCLUSIONS: The observed results back the suggestion
      that these three Plectranthus species represent a promising source of cytotoxic
      and antimicrobial agents.

PMID- 30097043
TI  - Using appropriate pre-pregnancy body mass index cut points for obesity in the
      Chinese population: a retrospective cohort study.
AB  - BACKGROUND: Appropriate classification of obesity is vital for risk assessment
      and complication prevention during pregnancy. We aimed to explore which pre
      pregnancy BMI cut-offs of obesity, either BMI >= 25 kg/m2 as recommended by the
      WHO for Asians or BMI >= 28 kg/m2 as suggested by the Working Group on Obesity in
      China (WGOC), best predicts the risk of adverse maternal and perinatal outcomes.
      METHODS: We retrospectively reviewed 11,494 medical records for live singleton
      deliveries in a tertiary center in Guangzhou, China, between January 2013 and
      December 2016. The primary outcomes included maternal obesity prevalence, adverse
      maternal and perinatal outcomes. Data were analyzed using the Chi-square test,
      logistic regression, and diagnostics tests. RESULTS: Among the study population,
      824 (7.2%) were obese according to the WHO criteria for Asian populations, and
      this would be reduced to 198 (1.7%) based on the criteria of WGOC. Obesity
      related adverse maternal and perinatal outcomes were gestational diabetes
      mellitus, preeclampsia, cesarean section, and large for gestational age (P <
      0.05). Compared to the WGOC criterion, the WHO for Asians criterion had a higher
      Youden index in our assessment of its predictive value in identifying risk of
      obesity-related adverse outcomes for Chinese pregnant women. Women in the BMI
      range of 25 to 28 kg/m2 are at high risks for adverse maternal and perinatal
      outcomes, which were similar to women with BMI >= 28 kg/m2. CONCLUSIONS: A lower
      pre-pregnancy BMI cutoff at 25 kg/m2 for defining obesity may be appropriate for
      pregnant women in South China. If WGOC standards are applied to pregnant Chinese
      populations, a significant proportion of at-risk patients may be missed.

PMID- 30097044
TI  - Preventing at-risk children from developing antisocial and criminal behaviour: a
      longitudinal study examining the role of parenting, community and societal
      factors in middle childhood.
AB  - BACKGROUND: Many childhood risk factors are known to be associated with
      children's future antisocial and criminal behaviour, including children's conduct
      disorders and family difficulties such as parental substance abuse. Some families
      are involved with many different services but little is known about what middle
      childhood factors moderate the risk of poor outcomes. This paper reports the
      quantitative component of a mixed methods study investigating what factors can be
      addressed to help families improve children's outcomes in the longer term. The
      paper examines six hypotheses, which emerged from a qualitative longitudinal
      study of the service experiences of eleven vulnerable families followed over five
      years. The hypotheses concern factors which could be targeted by interventions,
      services and policy to help reduce children's behaviour problems in the longer
      term. METHODS: The hypotheses are investigated using a sample of over one
      thousand children from the Avon Longitudinal Study of Parents and Children
      (ALSPAC). Multiple logistic regression examines associations between potentially
      moderating factors (at ages 5-10) and antisocial and criminal behaviour (at ages
      16-21) for children with behaviour problems at baseline. RESULTS: ALSPAC analyses
      support several hypotheses, suggesting that the likelihood of future antisocial
      and criminal behaviour is reduced in the presence of the following factors:
      reduction in maternal hostility towards the child (between ages 4 and 8),
      reduction in maternal depression (between the postnatal period and when children
      are age 10), mothers' positive view of their neighbourhood (age 5) and lack of
      difficulty paying the rent (age 7). The evidence was less clear regarding the
      role of social support (age 6) and mothers' employment choices (age 7).
      CONCLUSION: The findings suggest, in conjunction with findings from the separate
      qualitative analysis, that improved environments around the child and family
      during middle childhood could have long-term benefits in reducing antisocial and
      criminal behaviour.

PMID- 30097045
TI  - Impact of deformable image registration on dose accumulation applied
      electrocardiograph-gated 4DCT in the heart and left ventricular myocardium during
      esophageal cancer radiotherapy.
AB  - BACKGROUND: The deformable image registration (DIR) technique has the potential
      to realize the dose accumulation during radiotherapy. This study will analyze the
      feasibility of evaluating dose-volume parameters for the heart and left
      ventricular myocardium (LVM) by applying DIR. METHODS: The electrocardiograph
      gated four-dimensional CT (ECG-gated 4DCT) data of 21 patients were analyzed
      retrospectively. The heart and LVM were contoured on 20 phases of 4DCT (0%,
      5%,...,95%). The heart and LVM in the minimum volume/dice similarity coefficient
      (DSC) phase (Volume min/DSC min) were deformed to the maximum volume/DSC phase
      (Volume max/ DSC max), which used the intensity-based free-form DIR algorithm of
      MIM software. The dose was deformed according to the deformation vector. The
      variations in volume, mean dose (Dmean), V20, V30 and V40 for the heart and LVM
      before and after DIR were compared, and the reference phase was the Volume
      max/DSC max phase. RESULTS: For the heart, the difference between the pre- and
      post-registration Volume min and Volume max were reduced from 13.87 to 1.72%; the
      DSC was increased from 0.899 to 0.950 between the pre- and post-registration DSC
      min phase relative to the DSC max phase. The post-registration Dmean, V20, V30
      and V40 of the heart were statistically significant compared to those in the
      Volume max/DSC max phase (p < 0.05). For the LVM, the difference between the pre-
      and post-registration Volume min and Volume max were only reduced from 18.77 to
      17.38%; the DSC reached only 0.733 in the post-registration DSC min phase
      relative to the DSC max phase. The pre- and post-registration volume, Dmean, V20,
      V30 and V40 of the LVM were all statistically significant compared to those in
      the Volume max/DSC max phase (p < 0.05). CONCLUSIONS: There was no significant
      relationship between the variation in dose-volume parameters and the variation in
      the volume and morphology for the heart; however, the inconsistency of the
      variation in the volume and morphology for the LVM was a major factor that led to
      uncertainty in the dose-volume evaluation. In addition, the individualized local
      deformation registration technology should be applied in dose accumulation for
      the heart and LVM.

PMID- 30097046
TI  - Comparison of mothers and grandmothers physical and mental health and functioning
      within 6 months after child NICU/PICU death.
AB  - BACKGROUND: Losing a child is devastating for parents and grandparents. Family
      and friends generally focus on comforting and supporting the bereaved parents,
      unintentionally ignoring the bereaved grandparents. Grandmothers and grandfathers
      often struggle with wanting to help their adult children (deceased child's
      parents) without usurping the parents' responsibilities and decisions regarding
      the deceased child. Research on mothers' and grandmothers' health at about the
      same time after the same child's death in the neonatal or pediatric intensive
      care unit is lacking. The aim of this study was to compare mothers and
      grandmothers on physical health, mental health, and functioning in the first 1-6
      months after the same child's death in a neonatal or pediatric intensive care
      unit. METHODS: This cross-sectional secondary analysis compared 32 mothers with
      32 grandmothers of the same 32 deceased children (newborn-6 years). Grandmothers
      were recruited through these 32 mothers. Most grandmothers and mothers were
      Hispanic (25%, 34%) or Black (44%, 41%), respectively. Mothers and grandmothers
      separately completed questions about their Physical Health, Mental Health
      [depression (Beck Depression Inventory), Post-Traumatic Stress Disorder (PTSD,
      Impact of Events-R), grief (Hogan Grief Reaction Checklist)], and Functioning
      (social support [MSPSS] and Employment) since the child's/grandchild's death.
      Paired t-tests and Chi Square tests were used to compare grandmothers with
      mothers of the same deceased infant/child on their private and separate responses
      to study measures. RESULTS: Mothers had significantly more acute illnesses than
      grandmothers. More mothers (63%) than grandmothers (37%) were categorized as
      clinically depressed. More mothers (69%) than grandmothers (44%) had clinical
      PTSD. Mothers reported significantly higher levels of despair and detachment than
      grandmothers. Only 4 mothers and 2 grandmothers were in therapy at the time of
      interview. Grandmothers and mothers rated their ability to concentrate on their
      work and their level of social support similarly. CONCLUSIONS: Mothers had more
      acute illnesses, more severe depression, and a higher level of grief than
      grandmothers. However, few received therapy despite their high levels of
      depressive and PTSD symptoms.

PMID- 30097047
TI  - Evaluating the ability of a trauma team activation tool to identify severe
      injury: a multicentre cohort study.
AB  - BACKGROUND: Sensitive decision making tools should assist prehospital personnel
      in the triage of injured patients, identifying those who require immediate
      lifesaving interventions and safely reducing unnecessary under- and overtriage.
      In 2014 a new trauma team activation (TTA) tool was implemented in Central
      Norway. The overall objective of this study was to evaluate the ability of the
      new TTA tool to identify severe injury. METHODS: This was a multi-center
      observational cohort study with retrospective data analysis. All patients
      received by trauma teams at seven hospitals in Central Norway between 01.01.2015
      to 31.12.2015 were included. Severe injury was defined as Injury Severity Score
      (ISS) > 15. Overtriage was defined as the rate of patients with TTA and ISS < 15,
      whilst patients with TTA and ISS > 15 were defined as correctly triaged. RESULTS:
      A total of 1141 patients were identified, of which 998 were eligible for triage
      criteria analysis. Median age was 35 years (IQR 20-58) and the male proportion
      was 67%. Mechanism of injury was predominantly blunt trauma (96%) with transport
      related accidents (62%) followed by falls (22%) the most common. Overall, median
      injury severity score (ISS) was low and severely injured patients (ISS > 15)
      comprised 13% of the cohort. Utility of specific TTA criteria were: physiology
      20%, anatomical injury 21%, mechanism of injury (MOI) 53% and special causes 6%.
      Overtriage among all patients was 87%, and for those with physiologic criteria
      66%, anatomical injury 82%, mechanism of injury 97% and special causes criteria
      92%, respectively. CONCLUSIONS: Severe injury was infrequent and there was a
      substantial rate of overtriage. The ability of the TTA tool was relatively
      insensitive in identifying severe injury, but showed increased performance when
      utilizing physiologic and anatomical injury criteria. Many of the TTA mechanism
      of injury criteria might be considered for removal from the triage tool due to
      substantial rates of overtriage. This has relevance for the proposed development
      of national Norwegian TTA criteria.

PMID- 30097050
TI  - Wilms tumor, pleuropulmonary blastoma, and DICER1: case report and literature
      review.
AB  - BACKGROUND: Pleuroblastoma (PPB) is a rare pediatric tumor which, in 30% of
      cases, is associated with cystic nephroma. It has been recently linked to the
      DICER1 mutation as part of a predisposition syndrome for various tumors. However,
      if DICER 1 anomalies have been reported in patients with Wilms tumor (WT), to
      date, no cases of PPB, WT, and DICER1 mutations have been reported in the same
      patient. CASE PRESENTATION: We report the case of a 3-year-old patient, initially
      managed for metastatic WT. During his clinical course, the diagnosis of a PPB was
      made after detecting the DICER1 mutation and subsequent management was therefore
      modified. CONCLUSION: This case highlights that in case of simultaneous discovery
      of a renal tumor and a pulmonary lesion in a child, the DICER 1 mutations should
      be looked for as these could help adapt management and schedule the surgical
      procedures.

PMID- 30097049
TI  - ChromTime: modeling spatio-temporal dynamics of chromatin marks.
AB  - To model spatial changes of chromatin mark peaks over time we develop and apply
      ChromTime, a computational method that predicts peaks to be either expanding,
      contracting, or holding steady between time points. Predicted expanding and
      contracting peaks can mark regulatory regions associated with transcription
      factor binding and gene expression changes. Spatial dynamics of peaks provide
      information about gene expression changes beyond localized signal density
      changes. ChromTime detects asymmetric expansions and contractions, which for some
      marks associate with the direction of transcription. ChromTime facilitates the
      analysis of time course chromatin data in a range of biological systems.

PMID- 30097048
TI  - Structure of preantral follicles, oxidative status and developmental competence
      of in vitro matured oocytes after ovary storage at 4  degrees C in the domestic
      cat model.
AB  - BACKGROUND: Storage conditions during transportation of explanted ovaries are a
      critical step in setting up fertility preservation protocols in both animal and
      human fields. Here, we evaluated the effects of ovary storage at 4  degrees C on
      the preservation of preantral follicles and oocytes retrieved from antral
      follicles using the domestic cat as model. METHODS: Ovaries were harvested from
      fifty-five healthy domestic queens during ovariectomy and stored at 4  degrees C
      for 0 (control), 24, 48, 72 and 96 h. In Experiment 1, the effects of the storage
      period at 4  degrees C on the morphology, cytoskeleton (alpha/beta tubulin) and
      DNA integrity (phosphorylation of histone H2AX) of preantral follicles were
      investigated. In Experiment 2, oocytes recovered from antral follicles were
      matured and fertilized in vitro to evaluate their meiotic and developmental
      competence. Reactive oxygen species (ROS), glutathione (GSH) and lipid
      peroxidation were measured in matured oocytes. RESULTS: The results showed that:
      a) storage up to 24 h did not affect the morphology and the DNA integrity of
      preantral follicles; b) extended storage times caused progressive morphological
      abnormalities, disassembling of microtubules and DNA damage; c) storage up to 48
      h did not influence in vitro meiotic maturation of oocytes nor cleavage after in
      vitro fertilization. However, only oocytes stored within the ovary for 24 h
      produced blastocysts in a percentage similar to control oocytes; d) GSH levels of
      in vitro matured oocytes did not change at any time during ovary storage; a
      progressive increase in ROS levels was detected from 48 h associated with
      elevated lipid peroxidation at 72 and 96 h of storage. CONCLUSIONS: Storage of
      cat ovaries for up to 24 h caused minimal alteration of preantral follicles and
      oocytes. The extension of the storage period beyond 24 h progressively impaired
      the structure of follicles, and modified the oxidative status of in vitro matured
      oocytes and their developmental competence after in vitro fertilization. This
      information may help when setting up programs for fertility conservation,
      especially for wild feline species which die in geographic areas located far away
      from ARTs centers.

PMID- 30097051
TI  - Willingness to migrate-a potential effect of burnout? A survey of Hungarian
      physicians.
AB  - BACKGROUND: Burnout worldwide and migration of caregivers are among the most
      important challenges of the twenty-first century health care. METHODS:
      Quantitative, online survey of Hungarian physicians (n = 4 784) was performed in
      2013. A link to an anonymous, self-administered questionnaire was sent to all
      potential participants, namely to the registered members of the Hungarian Medical
      Chamber with a valid e-mail address. Linear regression analysis was used to
      determine the risk factors of burnout. The association between physicians'
      burnout and their willingness to migrate was determined by binary logistic
      regression analysis. RESULTS: Moderate/mild level of personal accomplishment was
      detected in 65% of respondents, whereas moderate/severe level of emotional
      exhaustion and depersonalization was detected in 49% and 46%, respectively.
      Single male physicians younger than 35 composed the cohort with the highest risk
      for developing burnout. Higher daily working hours and multiple workplaces
      contribute to the risk of developing burnout. According to logistic regression
      analysis, the intention to work abroad was affected by the emotional exhaustion
      dimension of burnout (OR = 1.432) and depersonalization had a tendency to have an
      impact on the willingness to migrate. CONCLUSIONS: We assume that there is a
      circular causality between burnout and the willingness to migrate. Burnout
      increases the willingness to work abroad, whereas contemplating migration might
      evoke a certain degree of depersonalization in caregivers who are in a dilemma.

PMID- 30097053
TI  - Young children with psychotic symptoms and risk for suicidal thoughts and
      behaviors: a research note.
AB  - OBJECTIVE: Suicidal thoughts and behaviors (STBs) are prevalent among youth with
      psychotic disorders (PD) relative to the general population. Recent research now
      suggests that STBs may present during the prodromal phase of the disease, or the
      clinical high risk (CHR) state. While this knowledge is important for the
      development of suicide prevention strategies in adolescent and adult populations,
      it remains unclear whether risk for suicide extends to children with or at risk
      for psychosis. The current study is an extension of previous work assessing STBs
      in youth across the psychosis continuum. We examine STBs in 37 CHR and PD
      children ages 7-13 years old, and further explore the prodromal symptom
      correlates of STB severity among CHR children. RESULTS: CHR and PD children
      endorsed STBs with a frequency and severity similar to what is observed in older
      CHR and PD populations. A number of children had never previously vocalized their
      suicidal plans or intent. Among CHR children, Social Anhedonia and Odd Behavior
      or Appearance were significantly correlated with STB severity. These findings
      underscore the importance of screening for STBs even in young children presenting
      with psychotic symptoms.

PMID- 30097052
TI  - Cardiovascular and inflammatory mechanisms in healthy humans exposed to air
      pollution in the vicinity of a steel mill.
AB  - BACKGROUND: There is a paucity of mechanistic information that is central to the
      understanding of the adverse health effects of source emission exposures. To
      identify source emission-related effects, blood and saliva samples from healthy
      volunteers who spent five days near a steel plant (Bayview site, with and without
      a mask that filtered many criteria pollutants) and at a well-removed College site
      were tested for oxidative stress, inflammation and endothelial dysfunction
      markers. METHODS: Biomarker analyses were done using multiplexed protein-array,
      HPLC-Fluorescence, EIA and ELISA methods. Mixed effects models were used to test
      for associations between exposure, biological markers and physiological outcomes.
      Heat map with hierarchical clustering and Ingenuity Pathway Analysis (IPA) were
      used for mechanistic analyses. RESULTS: Mean CO, SO2 and ultrafine particles
      (UFP) levels on the day of biological sampling were higher at the Bayview site
      compared to College site. Bayview site exposures "without" mask were associated
      with increased (p < 0.05) pro-inflammatory cytokines (e.g IL-4, IL-6) and
      endothelins (ETs) compared to College site. Plasma IL-1beta, IL-2 were increased
      (p < 0.05) after Bayview site "without" compared to "with" mask exposures.
      Interquartile range (IQR) increases in CO, UFP and SO2 were associated with
      increased (p < 0.05) plasma pro-inflammatory cytokines (e.g. IL-6, IL-8) and ET
      1(1-21) levels. Plasma/saliva BET-1 levels were positively associated (p < 0.05)
      with increased systolic BP. C-reactive protein (CRP) was positively associated (p
      < 0.05) with increased heart rate. Protein network analyses exhibited activation
      of distinct inflammatory mechanisms after "with" and "without" mask exposures at
      the Bayview site relative to College site exposures. CONCLUSIONS: These findings
      suggest that air pollutants in the proximity of steel mill site can influence
      inflammatory and vascular mechanisms. Use of mask and multiple biomarker data can
      be valuable in gaining insight into source emission-related health impacts.

PMID- 30097054
TI  - A new less invasive surgical technique in the management of acute Achilles tendon
      rupture through limited-open procedure combined with a single-anchor and
      "circuit" suture technique.
AB  - BACKGROUND: Traditional incision repair and minimally invasive repair for acute
      Achilles tendon repair have limitations. This study aimed to present our series
      of 23 patients with acute Achilles tendon rupture that was repaired using two
      small incisions to assist the anchor repair of the tear and a new "circuit"
      suture technique. METHODS: This was a retrospective study of 23 patients with
      acute Achilles tendon rupture treated with the new technique at Changhai Hospital
      between January 2015 and December 2016 and followed up for 14-33 months. Clinical
      outcome was assessed using the AOFAS, Leppilahti, and Arner-Lindholm scores.
      Complications, range of motion (ROM), and time to return to work and light sport
      activity were assessed. RESULTS: The AOFAS score was 85-96 at 3 months and 92-100
      at 12 months. The 3-month ROM was 27 degrees -37 degrees , and the 12-month ROM
      was 36 degrees -48 degrees . The Leppilahti score was 85-95 at 3 months and 90
      100 at 12 months. The recovery time of the patients was 10-18 weeks. The
      postoperative recovery time to exercise was 16-24 weeks. There was only one case
      of deep venous thrombosis. According to the Arner-Lindholm assessment criteria,
      patient outcomes were rated as excellent in 20 (87.0%) cases, good in three
      (13.0%) cases, and poor in 0 cases. The excellent-to-good rate was 100%.
      CONCLUSION: The limited-open procedure combined with a single-anchor and
      "circuit" suture technique could be used to repair torn Achilles sites, with a
      low occurrence of complications. This new and minimally invasive technique could
      be an alternative in the management of acute Achilles tendon rupture.

PMID- 30097055
TI  - PrPres deposition in the retina is a common finding of sporadic, familial and
      iatrogenic Creutzfeldt-Jakob diseases (CJD).

PMID- 30097056
TI  - Using acute tryptophan depletion to investigate predictors of treatment response
      in adolescents with major depressive disorder: study protocol for a randomised
      controlled trial.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are amongst the most
      prescribed antidepressants for adolescents with depressive symptoms and major
      depressive disorder. However, SSRIs have significant shortcomings as a first-line
      treatment considering that not all patients respond to these antidepressants.
      Amongst paediatric populations, meta-analyses indicate that up to approximately
      40% of patients do not respond, and for those who do show benefit, there is
      substantial heterogeneity in response onset. The neurotransmitter serotonin (5
      HT) plays a role in the clinical effectiveness and mechanisms of action of SSRIs.
      However, the exact and complete mechanism of action and reasons for the low
      response rate to SSRIs in some adolescent populations remains unknown. METHODS:
      To examine SSRI response and the role of 5-HT, this study will employ a
      randomised double-blind within subject, repeated measures design, recruiting
      adolescent patients with major depressive disorder. Participants will be
      subjected to acute tryptophan depletion (ATD) and the balanced control condition
      on two separate study days within a first study phase (Phase A), and the order in
      which these conditions (ATD/balanced control condition) occur will be random.
      This phase will be followed by Phase B, where participants will receive open
      label pharmacological treatment as usual with the SSRI fluoxetine and followed-up
      over a 12-week period. DISCUSSION: ATD is a neurodietary method typically used to
      investigate the impact of lowered brain 5-HT synthesis on mood and behaviour. The
      major hypothesis of this study is that ATD will be negatively associated with
      mood and cognitive functioning, therefore reflecting individual serotonergic
      sensitivity and related depressive symptoms. Additionally, we expect the
      aforementioned effects of ATD administration on mood to predict clinical
      improvement with regard to overall depressive symptomatology 12 weeks into SSRI
      treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials
      Registry (ANZCTR) ACTRN12616001561471 . Registered on 11 November 2016.

PMID- 30097057
TI  - Diffusible signal factor signaling regulates multiple functions in the
      opportunistic pathogen Stenotrophomonas maltophilia.
AB  - OBJECTIVE: Stenotrophomonas maltophilia is a Gram-negative bacterium commonly
      isolated from nosocomial infections. Analysis of the genome of the clinical S.
      maltophilia isolate K279a indicates that it encodes a diffusible signal factor
      (DSF)-dependent cell-cell signaling mechanism that is highly similar to the
      system previously described in phytopathogens from the genera Xanthomonas and
      Xylella. Our objective was to study the function of DSF signaling in the clinical
      strain S. maltophilia K279a using genetic and functional genomic analyses.
      RESULTS: We compared the wild-type strain with a mutant deficient in the rpfF
      (regulation of pathogenicity factors) gene that is essential for the synthesis of
      DSF. The effects of disruption of DSF signaling were pleiotropic with an impact
      on virulence, biofilm formation and pathogenesis. The phenotypic effects of rpfF
      mutation in S. maltophilia could be reversed by addition of exogenous DSF. Taken
      together, we demonstrate that DSF signaling regulates factors contributing to
      virulence, biofilm formation and motility of this important opportunistic
      pathogen.

PMID- 30097058
TI  - Single-cell RNAseq for the study of isoforms-how is that possible?
AB  - Single-cell RNAseq and alternative splicing studies have recently become two of
      the most prominent applications of RNAseq. However, the combination of both is
      still challenging, and few research efforts have been dedicated to the
      intersection between them. Cell-level insight on isoform expression is required
      to fully understand the biology of alternative splicing, but it is still an open
      question to what extent isoform expression analysis at the single-cell level is
      actually feasible. Here, we establish a set of four conditions that are required
      for a successful single-cell-level isoform study and evaluate how these
      conditions are met by these technologies in published research.

PMID- 30097060
TI  - Hunters and hunting across indigenous and colonist communities at the forest
      agriculture interface: an ethnozoological study from the Peruvian Amazon.
AB  - BACKGROUND: Wildlife has been traditionally used by forest communities as a
      source of protein, and the Peruvian Amazon is no exception. The articulation of
      colonist and indigenous communities to urban centers and markets results in
      changes in livelihood strategies and impacts on wildlife populations. To address
      the threat of overhunting and forest conversion, we provide a generalized
      characterization of colonist and indigenous communities and their hunting
      activities near Pucallpa, Ucayali, Peru. METHODS: A semi-structured household
      survey was conducted to characterize hunters and describe their prey collections.
      The data were analyzed by conducting a Kruskal-Wallis test, a multiple regression
      analysis, and by estimating the harvest rate (H). RESULTS: Less wealthy
      households were more actively engaged in hunting for food security and as a
      livelihood strategy. Additionally, older hunters were associated with higher
      hunting rates. Although the percentage of hunters was relatively low, estimated
      hunting rates suggest overharvesting of wildlife. Lowland pacas (Cuniculus paca)
      were the most frequently hunted prey, followed by red brocket deer (Mazama
      americana) and primates. While hunting intensity was not significantly different
      between indigenous and colonist communities, hunting rate disparities suggest
      there are different types of hunters (specialized vs. opportunistic) and that
      prey composition differs between communities. CONCLUSION: Close monitoring of
      wildlife populations and hunting activities is ideal for more accurately
      determining the impact of hunting on wildlife population and in turn on forest
      health. In lack of this type of information, this study provides insight of
      hunting as a shifting livelihood strategy in a rapidly changing environment at
      the forest/agriculture frontier.

PMID- 30097059
TI  - E90 subunit vaccine protects mice from Zika virus infection and microcephaly.
AB  - Zika virus (ZIKV) became a global threat due to its unprecedented outbreak and
      its association with congenital malformations such as microcephaly in developing
      fetuses and neonates. There are currently no effective vaccines or drugs
      available for the prevention or treatment of ZIKV infection. Although multiple
      vaccine platforms have been established, their effectiveness in preventing
      congenital microcephaly has not been addressed. Herein, we tested a subunit
      vaccine containing the 450 amino acids at the N-terminus of the ZIKV envelope
      protein (E90) in mouse models for either in utero or neonatal ZIKV infection. In
      one model, embryos of vaccinated dams were challenged with a contemporary ZIKV
      strain at embryonic day 13.5. The other model infects neonatal mice from
      vaccinated dams by direct injection of ZIKV into the developing brains. The
      vaccine led to a substantial reduction of ZIKV-infected cells measured in the
      brains of fetal or suckling mice, and successfully prevented the onset of
      microcephaly compared to unvaccinated controls. Furthermore, E90 could protect
      mice from ZIKV infection even at 140 days post-immunization. This work directly
      demonstrates that immunization of pregnant mice protects the developing brains of
      offspring both in utero and in the neonatal period from subsequent ZIKV infection
      and microcephaly. It also supports the further development of the E90 subunit
      vaccine towards clinical trials.

PMID- 30097061
TI  - Comparing atmospheric and hypoxic cultured mesenchymal stem cell transcriptome:
      implication for stem cell therapies targeting intervertebral discs.
AB  - BACKGROUND: Mesenchymal stem cells (MSCs) represent an attractive avenue for
      cellular therapies targeting degenerative diseases. MSC in vitro expansion is
      required in order to obtain therapeutic numbers during the manufacturing process.
      It is known that culture conditions impact cellular properties and behavior after
      in vivo transplantation. In this study, we aimed at evaluating the benefit of
      hypoxic culturing of human bone marrow derived mesenchymal stem cells on cell
      fitness and whole genome expression and discussed its implication on cellular
      therapies targeting orthopedic diseases such as chronic lower back pain. METHODS:
      Human bone marrow mesenchymal stem cells (hBMMSCs) were isolated from fresh human
      anticoagulated whole bone marrow and were cultured side by side in atmospheric
      (20% O2) and hypoxic (5% O2) oxygen partial pressure for up to 3 passages. Stem
      cell fitness was assessed by clonogenic assay, cell surface marker expression and
      differentiation potential. Whole genome expression was performed by mRNA
      sequencing. Data from clonogenic assays, cell surface marker by flow cytometry
      and gene expression by quantitative PCR were analyzed by two-tailed paired
      Student's t-test. Data from mRNA sequencing were aligned to hg19 using Tophat
      2.0.13 and analyzed using Cufflinks-2.1.1. RESULTS: Hypoxic culturing of hBMMSCs
      had positive effects on cell fitness, as evidenced by an increased clonogenicity
      and improved differentiation potential towards adipocyte and chondrocyte
      lineages. No difference in osteoblast differentiation or in cell surface markers
      were observed. Only a small subset of genes (34) were identified by mRNA
      sequencing to be significantly dysregulated by hypoxia. When clustered by
      biological function, these genes were associated with chondrogenesis and
      cartilage metabolism, inflammation and immunomodulation, cellular survival,
      migration and proliferation, vasculogenesis and angiogenesis. CONCLUSIONS:
      Hypoxic culturing positively impacted hBMMSCs fitness and transcriptome,
      potentially improving inherent properties of these cells that are critical for
      the development of successful cellular therapies. Hypoxic culturing should be
      considered for the in vitro expansion of hBMMSCs during manufacturing of cellular
      therapies targeting orthopedic disorders such as lower back pain.

PMID- 30097062
TI  - HBV infection increases the risk of macular degeneration: the roles of HBx
      mediated sensitization of retinal pigment epithelial cells to UV and blue light
      irradiation.
AB  - BACKGROUND: Hepatitis B virus (HBV) infection is strongly associated with
      hepatocellular carcinoma due to the main pathogenic X protein of HBV (HBx).
      Whether HBV infection and the HBx protein could result in macular degeneration
      (MD) is not known. The aim of this study is to assess the association and
      underlying mechanisms between HBV infection and MD. METHODS: The National Health
      Research Institutes in Taiwan built a large database, the National Health
      Insurance Research Database (NHIRD), which includes the claims data from the
      Taiwan National Health Insurance (NHI) program. The Taiwan NHI is a single-payer,
      compulsory health insurance program for Taiwan citizens. The data for the present
      study were derived from the Longitudinal Health Insurance Database, which
      contains the claims data of 1 million insured people within the NHIRD, including
      beneficiary registration, inpatient and outpatient files, drug use, and other
      medical services. In this study, we first investigated the association of HBV
      infection and the risk of MD by a population-based cohorts study enrolling 39,796
      HBV-infected patients and 159,184 non-HBV-infected patients. RESULTS: After
      adjustment of age, sex, and comorbidities, the risk of MD was significantly
      higher in the HBV-infected cohort than in the non-HBV-infected cohort (adjusted
      HR = 1.31; 95% CI = 1.17-1.46). In vitro, we provided evidence to demonstrate
      that overexpression of HBx in the human retinal pigment epithelial (RPE) cell
      line, ARPE19, significantly reduced cell viability and clonogenic survival upon
      UV and blue light irradiation. By gene microarray analysis, we further showed
      that almost all genes in DNA repair pathways including base excision repair,
      nucleotide excision repair, mismatch repair, and homologous recombination were
      significantly down-regulated in the UV-induced cell death of HBx-transfected
      ARPE19 cells. CONCLUSIONS: The HBx protein may sensitize RPE cells to UV and blue
      light irradiation and increase the risk of HBV-infection-associated MD through
      down-regulation of multiple DNA repair pathways.

PMID- 30097063
TI  - Investigating the causal relationship between employment and informal caregiving
      of the elderly.
AB  - OBJECTIVE: Examining the causal relationship between employment and informal
      caring to date has been impeded in countries like Ireland where there is a lack
      of suitable panel data and/or variables for instrument construction. This paper
      employs propensity score matching to control for non-random selection into
      treatment and control groups which controls for differences in employment
      outcomes between carers and non-carers in Ireland using data from Quarterly
      National Household Survey 2009 Quarter 3. Earlier papers focus on using
      regression techniques which may lead to biased estimates. RESULTS: Results
      suggest that differences exist between carers and non-carers with respect to
      their employment status in Ireland. Overall the results suggest that the effects
      are more significant for those providing greater hours of informal care per week
      than those providing fewer hours of care per week. The effects estimated in this
      paper are likely to be more precise as failing to account for potential biases in
      the relationship are likely to underestimate the true effect of caring on
      employment outcomes. We find that propensity score matching provides an
      alternative method of examining the relationship when suitable panel data and/or
      variables for instrument construction are not available.

PMID- 30097065
TI  - Quit outcomes among clients ineligible for cessation medication through the state
      quitline: a retrospective, observational study.
AB  - BACKGROUND: Distribution of tobacco cessation medications through state quitlines
      increases service utilization and quit outcomes. However, some state quitlines
      have moved to models in which callers are instructed to obtain quit medications
      through their health insurance pharmaceutical benefit. We aimed to investigate
      the impact of this policy on medication access and quit outcomes in the state
      quitline setting for clients who must obtain covered medications through the
      state Medicaid program. We hypothesized that clients with Medicaid who were
      referred by their healthcare provider would be more likely to report using quit
      medication and have higher quit rates compared to clients with Medicaid who
      engaged the quitline on their own. METHODS: An observational, retrospective study
      was conducted using state quitline clients with Medicaid health insurance who
      were ineligible for quitline provided cessation medications. Clients were
      stratified by referral type: self-referred, passively referred, and proactively
      referred. Unadjusted and adjusted logistic regression was used to estimate the
      effect of referral type on both quit status and cessation medication use.
      RESULTS: Proactively referred clients were less likely to use quit medication
      (53.6%) compared to self (56.9%) and passively referred clients (61.1%).
      Proactively referred clients had lower quit rates (31.4%), as compared to
      passively referred (36.0%) and self-referred (35.1%). In adjusted models,
      proactively referred clients were significantly less likely to be quit than
      passively referred clients (OR = 0.75, 95% CI: 0.56, 0.99). There were no
      statistically significant differences in medication use or number of coaching
      sessions among proactive, passive, and self-referred clients in adjusted models.
      CONCLUSIONS: In adjusted models, medication use did not significantly differ by
      mode of entry in this population of Medicaid beneficiaries. Psychosocial factors
      such as intention to quit in the next 30 days, social support for quitting,
      education level, race, and ethnicity impacted quit status and differed by mode of
      entry. Quitlines should use tailored strategies to increase engagement and reduce
      barriers among proactively referred clients.

PMID- 30097066
TI  - T. marneffei infection complications in an HIV-negative patient with pre-existing
      pulmonary sarcoidosis: a rare case report.
AB  - BACKGROUND: Talaromyces marneffei (T. marneffei) is a thermal dimorphic
      pathogenic fungus that often causes fatal opportunistic infections in human
      immunodeficiency virus (HIV)-infected patients. Although T. marneffei-infected
      cases have been increasingly reported among non-HIV-infected patients in recent
      years, no cases of T. marneffei infection have been reported in pulmonary
      sarcoidosis patients. In this case, we describe a T. marneffei infection in an
      HIV-negative patient diagnosed with pulmonary sarcoidosis. CASE PRESENTATION: A
      41-year-old Chinese man who had pre-existing pulmonary sarcoidosis presented with
      daily hyperpyrexia and cough. Following a fungal culture from bronchoalveolar
      lavage (BAL), the patient was diagnosed with T. marneffei infection. A high
      resolution computed tomography (HRCT) chest scan revealed bilateral lung diffuse
      miliary nodules, multiple patchy exudative shadows in the bilateral superior
      lobes and right inferior lobes, air bronchogram in the consolidation of the right
      superior lobe, multiple hilar and mediastinal lymphadenopathies and local pleural
      thickening. After 3 mos of antifungal therapy, the patient's pulmonary symptoms
      rapidly disappeared, and the physical condition improved markedly. A subsequent
      CT re-examination demonstrated that foci were absorbed remarkably after
      treatment. The patient is receiving follow-up therapy and assessment for a cure.
      CONCLUSION: This case suggested that clinicians should pay more attention to non
      HIV-related lung infections in patients with pulmonary sarcoidosis. Early
      diagnosis and treatment with antifungal therapy can improve the prognosis of T.
      marneffei infection.

PMID- 30097064
TI  - Effect of haemodiafiltration vs conventional haemodialysis on growth and
      cardiovascular outcomes in children - the HDF, heart and height (3H) study.
AB  - BACKGROUND: Cardiovascular disease is prevalent in children on dialysis and
      accounts for almost 30% of all deaths. Randomised trials in adults suggest that
      haemodiafiltration (HDF) with high convection volumes is associated with reduced
      cardiovascular mortality compared to high-flux haemodialysis (HD); however
      paediatric data are scarce. We designed the haemodiafiltration, heart and height
      (3H) study to test the hypothesis that children on HDF have an improved
      cardiovascular risk profile, growth and nutritional status and quality of life,
      compared to those on conventional HD. We performed a non-randomised parallel-arm
      intervention study within the International Paediatric Haemodialysis Network
      Registry comparing children on HDF and conventional HD to determine annualised
      change in cardiovascular end-points and growth. Here we present the 3H study
      design and baseline characteristics of the study population. METHODS: 190
      children were screened and 177 (106 on HD and 71 on HDF) recruited from 28
      centres in 10 countries. There was no difference in age, underlying diagnosis,
      comorbidities, previous dialysis therapy, dialysis vintage, residual renal
      function, type of vascular access or blood flow between HD and HDF groups. High
      flux dialysers were used in 63% of HD patients and ultra-pure water was available
      in 52%. HDF patients achieved a median convection volume of 13.3 L/m2; this was
      associated with the blood flow rate only ((p = 0.0004, r = 0.42) and independent
      of access type (p = 0.38). DISCUSSION: This is the largest study on dialysis
      outcomes in children that involves deep phenotyping across a wide range of
      cardiovascular, anthropometric, nutritional and health-related quality of life
      measures, to test the hypothesis that HDF leads to improved cardiovascular and
      growth outcomes compared to conventional HD. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT02063776 . The trial was prospectively registered on the
      14 Feb 2014.

PMID- 30097067
TI  - Citrulline malate supplementation does not improve German Volume Training
      performance or reduce muscle soreness in moderately trained males and females.
AB  - BACKGROUND: Use of supplements to aid performance is common practice amongst
      recreationally active individuals, including those without a sufficient evidence
      base. This investigation sought to assess whether acute supplementation with 8 g
      of citrulline malate (CM) (1.11: 1 ratio) would improve anaerobic performance.
      METHODS: A randomised double blind placebo control trial was employed, using a
      counterbalanced design. We recruited recreationally active men and women to take
      part in an isokinetic chair protocol, based on German Volume Training (GVT)
      whereby participants attempted to perform 10 sets of 10 repetitions against a
      force representing 70% of their peak concentric force. RESULTS: The number of
      repetitions achieved over the course of the GVT was 94.0 +/- 7.9 and 90.9 +/-
      13.9 for placebo and CM respectively. There was no significant difference between
      the placebo and CM treatment for number of repetitions (P = 0.33), isometric (P =
      0.60), concentric (P = 0.38), or eccentric (P = 0.65) peak force following the
      GVT. Total muscle soreness was significantly higher in the CM compared to the
      placebo treatment following the GVT protocol over 72 h (P = 0.01); although this
      was not accompanied by a greater workload/number of repetitions in the CM group.
      CONCLUSIONS: We conclude that an acute dose of CM does not significantly affect
      anaerobic performance using an isokinetic chair in recreational active
      participants. Practical implications include precaution in recommending CM
      supplementation. Coaches and athletes should be aware of the disparity between
      the chemical analyses of the products reviewed in the present investigation
      versus the manufacturers' claims.

PMID- 30097068
TI  - Comparative proteomic analysis of QTL CTS-12 derived from wild rice (Oryza
      rufipogon Griff.), in the regulation of cold acclimation and de-acclimation of
      rice (Oryza sativa L.) in response to severe chilling stress.
AB  - BACKGROUND: Rice (Oryza sativa L.) is a thermophilic crop vulnerable to chilling
      stress. However, common wild rice (Oryza rufipogon Griff.) in Guangxi (China) has
      the ability to tolerate chilling stress. To better understand the molecular
      mechanisms underlying chilling tolerance in wild rice, iTRAQ-based proteomic
      analysis was performed to examine CTS-12, a major chilling tolerance QTL derived
      from common wild rice, mediated chilling and recovery-induced differentially
      expressed proteins (DEPs) between the chilling-tolerant rice line DC90 and the
      chilling-sensitive 9311. RESULTS: Comparative analysis identified 206 and 155
      DEPs in 9311 and DC90, respectively, in response to the whole period of chilling
      and recovery. These DEPs were clustered into 6 functional groups in 9311 and 4 in
      DC90. The majority were enriched in the 'structural constituent of ribosome',
      'protein-chromophore linkage', and 'photosynthesis and light harvesting'
      categories. Short Time-series Expression Miner (STEM) analysis revealed distinct
      dynamic responses of both chloroplast photosynthetic and ribosomal proteins
      between 9311 and DC90. CONCLUSION: CTS-12 might mediate the dynamic response of
      chloroplast photosynthetic and ribosomal proteins in DC90 under chilling (cold
      acclimation) and recovery (de-acclimation) and thereby enhancing the chilling
      stress tolerance of this rice line. The identified DEPs and the involvement of
      CTS-12 in mediating the dynamic response of DC90 at the proteomic level
      illuminate and deepen the understanding of the mechanisms that underlie chilling
      stress tolerance in wild rice.

PMID- 30097069
TI  - The combined effect of non-alcoholic fatty liver disease and metabolic syndrome
      on colorectal carcinoma mortality: a retrospective in Chinese females.
AB  - BACKGROUND: This research aimed to investigate whether metabolic syndrome (MetS)
      and non-alcoholic fatty liver disease (NAFLD) had both individual and synergistic
      effects on the prognosis for female colorectal carcinoma (CRC) patients. METHODS:
      The relationship between CRC prognosis and NAFLD as well as MetS was evaluated in
      764 female participants. Based on the NAFLD level, patients were divided into
      significant NAFLD (SNAFLD), "moderate" and "severe" level, and non-SNAFLD, "non"
      and "mild" level. All the patients were categorized into four subgroups according
      to the status of SNAFLD and MetS and then a comparison of CRC prognosis among
      those four groups was performed. RESULTS: NAFLD, SNAFLD, and MetS were
      independent factors for CRC-specific mortality with the adjustment of age and
      other confounders. The hazard ratio (HR) of CRC-specific mortality in MetS (+)
      SNAFLD (+) group was significantly higher than that in other three groups.
      Relative excess risk of interaction (RERI) was 2.203 with 95% CI ranged from
      0.197 to 4.210, attributable proportion (AP) was 0.444 with range from 0.222 to
      0.667, and synergy index (SI) of 2.256 with 95% CI from 1.252 to 4.065,
      indicating SNAFLD and MetS had a significant synergic effect on CRC-specific
      mortality. CONCLUSIONS: SNAFLD and MetS are independent risk factors for CRC
      specific mortality in females. Moreover, those two diseases have a synergistic
      effect on promoting CRC-specific mortality.

PMID- 30097070
TI  - Prospective comparison of various radiological response criteria and pathological
      response to preoperative chemotherapy and survival in operable high-grade soft
      tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304.
AB  - BACKGROUND: Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of
      preoperative chemotherapy for STS is evaluated using various tumor size-based
      radiological response criteria. However, it is still unclear which set of
      criteria would show the best association with pathological response and survival
      of the patients with STS. METHODS: We compared radiological responses to
      preoperative chemotherapy for operable STS by the Response Evaluation Criteria in
      Solid Tumors (RECIST), modified RECIST, World Health Organization criteria,
      Japanese Orthopaedic Association criteria, and modified Choi criteria and
      analyzed the association with pathological response and survival using the data
      from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical
      trial evaluating the efficacy of perioperative chemotherapy for STS in the
      extremities. RESULTS: Seventy eligible patients in JCOG0304 were analyzed. The
      results demonstrated that none of the size-based radiological response criteria
      showed significant association with pathological response to preoperative
      chemotherapy for STS. The difference between overall survival of the patients
      assessed as partial response and stable disease/progressive disease by RECIST was
      not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50.
      All other response criteria also could not exhibit significant association
      between radiological responses and survival. CONCLUSION: In the present study,
      none of the radiological response criteria analyzed demonstrated association of
      response to preoperative chemotherapy with pathological response or survival of
      the patients with operable STS. Further prospective investigation is required to
      develop criteria to evaluate not only tumor shrinkage but biological effects of
      preoperative chemotherapy for the patients with localized STS. TRIAL
      REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August,
      2005 (retrospectively registered).

PMID- 30097072
TI  - Log Transformation and the Effect on Estimation, Implication, and Interpretation
      of Mean and Measurement Uncertainty in Microbial Enumeration.
AB  - Background: Estimation of measurement uncertainty (MU) has been extensively
      addressed in documents from standard authorities. In microbiology, bacterial
      counts are log transformed to get a more normal distribution. Unfortunately, the
      difference between using original and log-transformed data appears to not have
      been investigated even in publications focusing on MU estimation. Method:
      Statistical formulae inferencing and estimation of MU using real bacterial
      enumeration datasets. Results: Both mean and SD calculated from original data
      carry the same scale and unit as the original data. However, the mean of log
      transformed data becomes a geometric mean in log, and the SD becomes the
      logarithm of a ratio. Furthermore, calculation of RSD obtained by dividing the SD
      by the mean is meaningless and misleading for log-transformed data. The ratio,
      the antilog of the SD of log-transformed data, copes with multiplicative and
      divisive relationships to geometric mean (without log), instead of the arithmetic
      mean. The ratio can be converted to an analog ratio, which is similar or almost
      identical to the RSD of the untransformed data, especially when the within
      subject variation is small. When MU is estimated from multiple samples with
      different measurands, the calculated RSD of original data is independent of the
      mean and can be pooled; however, for log-transformed data, the SD can be combined
      to estimate the common uncertainty. Conclusions: Calculation and use of RSD of
      log-transformed data are meaningless and misleading. Procedures outlining the
      estimation and interpretation of MU from log-transformed data require re
      evaluation.

PMID- 30097073
TI  - Inductively Coupled Plasma Collision Cell Quadrupole Mass Spectrometric
      Determination of Extractible Arsenic, Cadmium, Chromium, Lead, Mercury, and Other
      Elements in Food Using Microwave-Assisted Digestion: Results from an FDA
      Interlaboratory Study.
AB  - Background: An interlaboratory study was conducted to test U.S. Food and Drug
      Administration (FDA) Elemental Analysis Manual (EAM) Method 4.7, "Inductively
      Coupled Plasma-Mass Spectrometric Determination of Arsenic, Cadmium, Chromium,
      Lead, Mercury, and Other Elements in Food Using Microwave Assisted Digestion."
      Objective: The goal of the study was to demonstrate the performance of FDA EAM
      Method 4.7. Methods: Fourteen laboratories participated in the collaborative
      study, including nine Food Emergency Response Network state laboratories and five
      federal FDA laboratories. Laboratories tested 8 labeled standard reference
      materials and 12 blinded foods: mayonnaise, dark chocolate, sunflower seeds,
      hamburger with cheese, brown rice flour (blinded reference material included as a
      test food), infant formula, canned smoked oysters, sardines in tomato paste,
      swordfish, mineral water, cinnamon, and a multivitamin. The blinded test foods
      represented every sector of the AOAC food triangle. Participants measured the
      mass fraction of each element in each sample in triplicate. Results: Horwitz
      Ratio (HorRat) values were better than 1.5 for all As, Cd, Cu, Hg, Mo, Ni, Pb,
      and Se measurements when at least eight laboratories reported results greater
      than LOQ. The HorRat values were better than 1.5 for all Mn and Zn measurements
      except for the multivitamin and for all Cr measurements except for sunflower
      seeds, in which the nonhomogeneity was identified. The average HorRat value of
      the blinded test foods was 0.66 for results greater than LOQ (n = 4206).
      Conclusions: The study showed that the method performed satisfactorily as a
      standard method for extractible elemental analysis of food. Highlights: The
      method met or exceeded the performance expected.

PMID- 30097074
TI  - Eco-Friendly Green Liquid Chromatographic Determination of Azelastine in the
      Presence of its Degradation Products: Applications to Degradation Kinetics.
AB  - Background: Green solvents such as microemulsion were used in the proposed method
      because they play a vital role in the analytical method's influence on the
      environment. Objective: A highly sensitive, specific, and validated stability
      indicating eco-friendly green microemulsion liquid chromatography (MELC) method
      was developed for separation of the antihistaminic drug Azelastine HCl (AZL) from
      its degradation products with application to degradation kinetics. Methods:
      Chromatographic separation was operated on a C18 column with a microemulsion
      mobile phase, which consists of 0.1 M sodium dodecyl sulphate, 10% n-propanol, 1%
      n-octanol, and 0.3% triethylamine, by using 0.02 M phosphoric acid at pH 3.5 and
      irbesartan as internal standard. The eluted compounds were monitored at 210 nm
      with flow rate 1 mL/min at ambient temperature. Results: A linear dependence of
      the peak area on drug concentration over the concentration range of 0.1 to 25
      MUg/mL was achieved with an LOD of 0.04 MUg/mL and an LOQ of 0.10 MUg/mL.
      Moreover, the proposed method was successfully applied for determination of AZL
      in eye drops and metered dose nasal inhaler as well as to study the kinetics of
      alkaline, acidic, neutral, oxidative, and photolytic degradation processes of AZL
      according to the International Council for Harmonization guidelines. Conclusions:
      The proposed method could be used as a harmless alternative for quality control
      analysis of the mentioned drug, without interference from dosage form additives
      or decomposition products. Highlights: A highly sensitive stability-indicating
      eco-friendly green MELC method was developed for the separation of the
      antihistaminic drug AZL from its degradation products.

PMID- 30097071
TI  - Homeobox oncogene activation by pan-cancer DNA hypermethylation.
AB  - BACKGROUND: Cancers have long been recognized to be not only genetically but also
      epigenetically distinct from their tissues of origin. Although genetic
      alterations underlying oncogene upregulation have been well studied, to what
      extent epigenetic mechanisms, such as DNA methylation, can also induce oncogene
      expression remains unknown. RESULTS: Here, through pan-cancer analysis of 4174
      genome-wide profiles, including whole-genome bisulfite sequencing data from 30
      normal tissues and 35 solid tumors, we discover a strong correlation between gene
      body hypermethylation of DNA methylation canyons, defined as broad under
      methylated regions, and overexpression of approximately 43% of homeobox genes,
      many of which are also oncogenes. To gain insights into the cause-and-effect
      relationship, we use a newly developed dCas9-SunTag-DNMT3A system to methylate
      genomic sites of interest. The locus-specific hypermethylation of gene-body
      canyon, but not promoter, of homeobox oncogene DLX1, can directly increase its
      gene expression. CONCLUSIONS: Our pan-cancer analysis followed by functional
      validation reveals DNA hypermethylation as a novel epigenetic mechanism for
      homeobox oncogene upregulation.

PMID- 30097075
TI  - Eosinophilic esophagitis 25 years after its recognition: Where do we stand?

PMID- 30097076
TI  - Thoughts on how to do the right thing.

PMID- 30097077
TI  - Anatomy of the Subtalar Joint.
AB  - The subtalar joint is divided into the talocalcaneonavicular and the
      talocalcaneal joint, separated by a conical interosseous tunnel (canalis and
      sinus tarsi). The talocalcaneonavicular joint is a ball-and-socket articulation
      (coxa pedis). An important part of the coxa pedis is the spring ligament. The
      canalis and sinus tarsi are occupied by the roots of the inferior extensor
      retinaculum, cervical ligament, interosseous talocalcaneal ligament, and anterior
      talocalcaneal ligament. Three-dimensional motion in the subtalar joint complex
      (eversion/inversion) is guided by the axial alignment of the talus, calcaneus,
      and navicular; the ligaments; and the shape of the articular surfaces.

PMID- 30097078
TI  - Subtalar Joint Biomechanics: From Normal to Pathologic.
AB  - Subtalar joint biomechanics are primarily driven by the shape of the
      articulations with contributions from the surrounding soft tissues. The joint
      motion occurs about a single axis oriented medially and superiorly. Joint contact
      forces change during different stages of gait and are affected by hindfoot
      alignment and traumatic alterations to their normal anatomy. A valgus subtalar
      joint axis is likely a contributing, and perhaps primary, risk factor for
      progression to adult acquired flat foot. The subtalar joint axis also contributes
      to the clinical picture of a cavus foot and a special subset of patients with
      dynamic varus.

PMID- 30097080
TI  - Fractures of the Lateral Process of the Talus.
AB  - Lateral talar process fractures (LTPF) are uncommon injuries but have become more
      relevant with snowboarding. Currently the fractures are classified according to
      McCrory-Bladin into 3 types, with advice for treatment that is not ideal anymore.
      This article proposes modifying the existing classification by differentiating
      the multifragmented type III into 3 subtypes: IIIa, articular multifragmented but
      metaphyseal simple; IIIb, articular and metaphyseal multifragmented but
      reconstructable; and type IIIc, comminuted and nonreconstructable. A treatment
      algorithm is presented. Undisplaced fractures are usually treated conservatively
      and displaced are an indication for surgery. In general, the outcome is good to
      excellent, if timely diagnosed and adequately treated.

PMID- 30097079
TI  - Traumatic Injury to the Subtalar Joint.
AB  - Traumatic injury to the subtalar joint occurs during subtalar dislocations, talar
      and calcaneal fractures, and fracture-dislocations. After closed reduction of
      subtalar dislocations, peripheral talar or calcaneal fractures need to be ruled
      out by computed tomography scanning. In fractures and fracture-dislocations of
      the talus and calcaneus involving the subtalar joint, anatomic reconstruction of
      joint congruity is essential for functional rehabilitation. Failure to
      anatomically reduce the subtalar joint potentially leads to chronic instability,
      subtalar arthritis and posttraumatic hindfoot deformity. Despite adequate
      management, subtalar arthritis may develop as a result of primary cartilage
      damage at the time of injury.

PMID- 30097081
TI  - Update on Subtalar Joint Instability.
AB  - Subtalar joint stability is ensured by the osseous geometry of the talocalcaneal
      joint and the complex array of the ligaments at the medial and lateral aspect of
      the ankle joint, the sinus and canalis tarsi, and the talocalcaneonavicular
      joint, respectively. There is still a substantial lack of knowledge about the
      interaction of the ankle and subtalar joint complex. Subtalar joint instability
      appears to be more frequent than is generally assumed. The diagnosis of chronic
      subtalar joint instability makes the application of a comprehensive algorithm
      necessary. There is ongoing debate about the preferable techniques for
      restoration of subtalar joint stability.

PMID- 30097082
TI  - Arthroereisis: What Have We Learned?
AB  - One of the most common orthopedic problems in the authors' practice is flatfoot
      and, although it is most commonly treated conservatively, there is still lack of
      consensus about the type of surgical treatment that is best recommended in a
      specific patient. Keeping in mind that medial soft tissue reconstruction alone
      has not proved enough as an isolated procedure and that osteotomies and
      arthrodesis are considered more invasive surgery, arthroereisis is a quick, easy,
      and reproducible technique that seems to have good results without major
      complications in the correct patient. Indications, biomechanical principles, and
      technique are described in this article.

PMID- 30097083
TI  - Coalitions of the Tarsal Bones.
AB  - Tarsal coalitions are the result of impaired mesenchymal separation of the tarsal
      bones. The most common types include calcaneonavicular or talocalcaneal
      coalitions. Subtalar stiffness results in pathologic kinematics with increased
      risk of ankle sprains, planovalgus foot deformity, and progressive joint
      degeneration. Resection of the coalition yields good results. Tissue
      interposition may reduce the risk of reossification, and concomitant deformity
      should be addressed in the same surgical setting.

PMID- 30097084
TI  - Medial Approach to the Subtalar Joint.
AB  - Surgical access to the subtalar joint is required in a plethora of pathologic
      conditions of the hindfoot. The conventional lateral approach can give excellent
      access to subtalar joint; however, in hindfoot valgus deformities, there can be
      unacceptable risks of wound problems and incomplete deformity corrections. The
      medial approach offers good access to the subtalar joint with an increasing
      evidence base for its use, especially with double fusions in pes planus
      deformities. The authors review the current evidence in the use of the medial
      approach for the subtalar joint.

PMID- 30097086
TI  - Subtalar Arthroscopic Fusion.
AB  - Arthroscopic subtalar fusion is an excellent approach to subtalar pathologic
      condition where conservative treatment has failed and a fusion has been
      indicated. Formal contraindications include excessive malalignment and bone loss.
      The posterior arthroscopic approach is analyzed in this article, including
      indications, surgical technique, surgical tips, and complications. Excellent
      results can be expected, including a shorter time to fusion, and faster
      rehabilitation, including activities of daily living and sports.

PMID- 30097085
TI  - Open Technique for In Situ Subtalar Fusion.
AB  - The subtalar joint plays an important role for the hindfoot when accommodating
      during gait. Joint degeneration may be caused by posttraumatic, inflammatory, and
      pathologic biomechanical changes. Once conservative treatment has failed,
      subtalar fusion should be considered. The indication for surgery is based on
      thorough clinical and radiographic evaluation. Several techniques for subtalar
      fusion are published in literature. This article aims to describe a technique for
      in situ arthrodesis of the subtalar joint, paying special attention to
      biomechanical aspects as well as preoperative clinical and radiological work-up.

PMID- 30097087
TI  - Subtalar Distraction Arthrodesis.
AB  - The subtalar joint can be altered in its anatomy and biomechanical behavior. It
      is important to know how to assess the talar declination angle in order to assess
      the deformity at the subtalar joint. Consider a straight posterior approach to
      the subtalar joint and remain liberal in the use of z-shaped Achilles tendon
      lengthening. A structural bone graft should be used to elevate the talus.
      Positioning screws should be used to lock the construct.

PMID- 30097088
TI  - The Subtalar Joint.

PMID- 30097089
TI  - Atlas of the Radical SAM Superfamily: Divergent Evolution of Function Using a
      "Plug and Play" Domain.
AB  - The radical SAM superfamily contains over 100,000 homologous enzymes that
      catalyze a remarkably broad range of reactions required for life, including
      metabolism, nucleic acid modification, and biogenesis of cofactors. While the
      highly conserved SAM-binding motif responsible for formation of the key 5'
      deoxyadenosyl radical intermediate is a key structural feature that simplifies
      identification of superfamily members, our understanding of their structure
      function relationships is complicated by the modular nature of their structures,
      which exhibit varied and complex domain architectures. To gain new insight about
      these relationships, we classified the entire set of sequences into similarity
      based subgroups that could be visualized using sequence similarity networks. This
      superfamily-wide analysis reveals important features that had not previously been
      appreciated from studies focused on one or a few members. Functional information
      mapped to the networks indicates which members have been experimentally or
      structurally characterized, their known reaction types, and their phylogenetic
      distribution. Despite the biological importance of radical SAM chemistry, the
      vast majority of superfamily members have never been experimentally characterized
      in any way, suggesting that many new reactions remain to be discovered. In
      addition to 20 subgroups with at least one known function, we identified
      additional subgroups made up entirely of sequences of unknown function.
      Importantly, our results indicate that even general reaction types fail to track
      well with our sequence similarity-based subgroupings, raising major challenges
      for function prediction for currently identified and new members that continue to
      be discovered. Interactive similarity networks and other data from this analysis
      are available from the Structure-Function Linkage Database.

PMID- 30097090
TI  - TYW1: A Radical SAM Enzyme Involved in the Biosynthesis of Wybutosine Bases.
AB  - Transfer RNA is extensively modified by the actions of a variety of enzymes. The
      radical S-adenosyl-l-methionine enzyme TYW1 modifies tRNAPhe forming the
      characteristic tricyclic ring via the condensation of carbons 2 and 3 of
      pyruvate. This chapter details methods that are required for studies of TYW1.

PMID- 30097091
TI  - Mechanistic Studies on the Radical SAM Enzyme Tryptophan Lyase (NosL).
AB  - Tryptophan lyase (NosL) is a radical SAM enzyme that catalyzes the formation of 3
      methyl-2-indolic acid from l-tryptophan in the biosynthesis of the antibiotic
      nosiheptide. NosL is the newest addition to the radical SAM-dependent aromatic
      amino acid lyase subfamily which includes ThiH, HydG, and CofH. The recently
      solved crystal structure of NosL challenged the previously accepted mechanistic
      hypothesis and spurred a renewed interest in investigating the reaction. This led
      to a series of studies that unraveled several fascinating aspects of the
      fragmentation-recombination reaction. This chapter describes the various
      methodologies used for the overexpression of NosL, its purification, in vitro
      reconstitution, preparation of isotopically labeled substrates, and
      chemoenzymatic synthesis of substrate analogs. The methods described here can be
      used to further investigate other aromatic amino acid lyases as well as
      reactivity of fleeting radicals in enzymology.

PMID- 30097092
TI  - Aminofutalosine Synthase (MqnE): A New Catalytic Motif in Radical SAM Enzymology.
AB  - Aminofutalosine synthase (MqnE) is a radical SAM enzyme involved in the
      futalosine-dependent menaquinone biosynthetic pathway. Its ability to add the 5'
      deoxyadenosyl radical to the substrate-rather than abstract a hydrogen atom-and
      to catalyze radical addition to a stable benzene ring gives it a unique place in
      the radical SAM superfamily and required the development of new strategies for
      trapping radical intermediates. This chapter describes the methodologies used for
      enzyme overexpression, purification, and in vitro reconstitution. We also
      describe the development of fast, radical triggered, carbon-halogen bond
      fragmentation reactions for the trapping of intermediates. We anticipate that
      these methods will be of general use in the study of other transient enzymatic
      radicals.

PMID- 30097093
TI  - Iterative Methylations Resulting in the Biosynthesis of the t-Butyl Group
      Catalyzed by a B12-Dependent Radical SAM Enzyme in Cystobactamid Biosynthesis.
AB  - B12-dependent radical SAM enzymes that can perform methylations on sp3 carbon
      centers are important for functional diversity and regulation of biological
      activity in several nonribosomal peptides. Detailed studies on these enzymes are
      hindered by the complexity of the substrates and low levels of expression of
      active enzymes. CysS can catalyze iterative methylations of a methoxybenzene
      moiety during the biosynthesis of the cystobactamids. Here, we describe the
      overexpression, purification, substrate identification, and mechanism of this
      enzyme.

PMID- 30097094
TI  - Biochemical Approaches for Understanding Iron-Sulfur Cluster Regeneration in
      Escherichia coli Lipoyl Synthase During Catalysis.
AB  - Lipoyl synthase (LipA in bacteria) is a radical S-adenosylmethionine (SAM) enzyme
      that catalyzes the second step of the de novo biosynthesis of the lipoyl
      cofactor: the insertion of sulfur at C6 and C8 of a pendant octanoyl chain. In
      addition to the [4Fe4S] cluster that is characteristic of the radical SAM (RS)
      enzymes, LipA contains a second [4Fe4S] cluster that, though controversial, has
      been proposed to be degraded during turnover to supply the inserted sulfur atoms.
      A consequence of this proposed role is that the destruction of its iron-sulfur
      cluster renders the enzyme in an inactive state. Recently, it was shown that
      Escherichia coli proteins NfuA or IscU can confer catalytic properties to E. coli
      LipA in vitro. In this chapter, we present methods for characterizing LipA and
      analyzing its activity in vitro, and provide strategies to monitor the pathway
      for the regeneration of LipA's auxiliary cluster by E. coli iron-sulfur carrier
      protein NfuA.

PMID- 30097095
TI  - Using Peptide Mimics to Study the Biosynthesis of the Side-Ring System of
      Nosiheptide.
AB  - Thiopeptide natural products have gained interest recently for their diverse
      pharmacological properties, including antibacterial, antifungal, anticancer, and
      antimalarial activities. Due to their inherent poor solubility and uptake, there
      is interest in developing new thiopeptides that mimic these unique structures,
      but which exhibit better pharmacokinetic properties. One strategy is to exploit
      the biosynthetic pathways using a chemoenzymatic approach to make analogs.
      However, a complete understanding of thiopeptide biosynthesis is not available,
      especially for those molecules that contain a large number of modifications to
      the thiopeptide core. This gap in knowledge and the lack of a facile method for
      generating a variety of thiopeptide intermediates makes studying particular
      enzymatic steps difficult. We developed a method to produce thiopeptide mimics
      based on established synthetic procedures to study the reaction catalyzed by
      NosN, the class C radical S-adenosylmethionine methylase involved in carbon
      transfer to C4 of 3-methylindolic acid and completion of the side-ring system in
      nosiheptide. Herein, we detail strategies for overproducing and isolating NosN,
      as well as procedures for synthesizing substrate mimics to study the formation of
      the side-ring system of nosiheptide.

PMID- 30097096
TI  - Mechanistic Studies of Radical SAM Enzymes: Pyruvate Formate-Lyase Activating
      Enzyme and Lysine 2,3-Aminomutase Case Studies.
AB  - The radical SAM enzyme superfamily is large and diverse, with ever-increasing
      numbers of examples of characterized reactions. This chapter focuses on the
      methodology we have developed over the last 25 years for working with these
      enzymes, with the specific examples discussed being the pyruvate formate-lyase
      activating enzyme (PFL-AE) and lysine 2,3-aminomutase (LAM). Both enzymes are
      purified from overexpressing Escherichia coli, but differ in that PFL-AE is
      expressed without an affinity tag and does not require iron-sulfur cluster
      reconstitution, while LAM purification is carried out through use of a His6
      affinity tag and the enzyme benefits from cluster reconstitution. Because of
      radical SAM enzymes' catalytic need for a [4Fe-4S] cluster, we present methods
      for characterization and incorporation of a full [4Fe-4S] cluster in addition to
      enzyme activity assay protocols. Synthesis of SAM (S-adenosyl-l-methionine) and
      its analogs have played an important role in our mechanistic studies of radical
      SAM enzymes, and their synthetic methods are also presented in detail.

PMID- 30097097
TI  - Determining Redox Potentials of the Iron-Sulfur Clusters of the AdoMet Radical
      Enzyme Superfamily.
AB  - While protein film electrochemistry (PFE) has proven to be an effective tool in
      the interrogation of redox cofactors and assessing the electrocatalytic activity
      of many different enzymes, recently it has been proven to be useful for the study
      of the redox potentials of the cofactors of AdoMet radical enzymes (AREs). In
      this chapter, we review the challenges and opportunities of examining the redox
      cofactors of AREs in a high level of detail, particularly for the deconvolution
      of redox potentials of multiple cofactors. We comment on how to best assess the
      electroactive nature of any given ARE, and we see that when applied well, PFE
      allows for not only determining redox potentials, but also determining proton
      coupling and ligand-binding phenomena in the ARE superfamily.

PMID- 30097098
TI  - Radical S-Adenosyl-l-Methionine (SAM) Enzyme Involved in the Maturation of the
      Nitrogenase Cluster.
AB  - Nitrogenase is the only known enzymatic system that converts atmospheric
      dinitrogen (N2) into bioavailable ammonia (NH3). The active-site cofactor
      responsible for this reactivity is a [(R-homocitrate)MoFe7S9C] cluster that is
      designated as the M-cluster. This important cofactor is assembled stepwise from a
      pair of [Fe4S4] clusters that become fused into a [Fe8S9C] core before additional
      refinements take place to complete the biosynthesis. NifB, a member of the
      radical S-adenosyl-l-methionine (SAM) superfamily, facilitates the conversion of
      the [Fe4S4] clusters (called the K-cluster) to the [Fe8S9C] core (called the L
      cluster). This transformation includes a SAM-dependent carbide insertion with
      concomitant incorporation of an additional sulfur. While difficulties with the
      purification of NifB have historically prevented detailed biochemical analyses,
      we have developed a heterologous expression system in Escherichia coli that
      yields stable NifB proteins from various N2-fixing methanogenic organisms that
      can be used for studies. This chapter details the procedures necessary to prepare
      an active NifB protein. The methods used for the biochemical characterization of
      the SAM-dependent carbide insertion reactions are also described.

PMID- 30097099
TI  - Purification, Characterization, and Biochemical Assays of Biotin Synthase From
      Escherichia coli.
AB  - Biotin synthase (BioB) catalyzes the oxidative insertion of a sulfur atom between
      the C6 methylene and the C9 methyl positions in dethiobiotin. The enzyme couples
      oxidation of each carbon position to reduction of the S-adenosyl-l-methionine
      (SAM) sulfonium center, generating 5'-deoxyadenosine and l-methionine, products
      that are characteristic of enzymes from the radical SAM superfamily. In bacteria,
      biotin biosynthesis is tightly regulated by the dual-function BirA
      repressor/holocarboxylase synthetase, resulting in very low levels of all biotin
      biosynthetic enzymes such that activity-based purification of BioB from the
      native organism is virtually impossible. However, overexpression and purification
      of recombinant BioB from E. coli are straight forward and, in contrast with many
      radical SAM enzymes, can be carried out under aerobic conditions. The active
      enzyme contains two iron-sulfur clusters, and the characterization and
      manipulation of these clusters are essential for a thorough understanding of
      enzyme catalysis and stability. An optimized in vitro assay for BioB is described
      herein that requires use of an auxiliary protein reducing system and must be
      carried out under anaerobic conditions to prevent oxidative damage to the reduced
      iron-sulfur clusters. Three methods for detection of biotin are described, with
      discussion of the advantages and limitations of each method. Challenges that may
      be encountered in adapting these assays to other organisms are also discussed.

PMID- 30097100
TI  - Methods for Expression, Purification, and Characterization of PqqE, a Radical SAM
      Enzyme in the PQQ Biosynthetic Pathway.
AB  - PqqE is the first enzyme in the biosynthetic pathway of the redox cofactor
      pyrroloquinoline quinone (PQQ), catalyzing the formation of a carbon-carbon bond
      in the precursor peptide PqqA. PqqE is a radical S-adenosyl-l-methionine (SAM)
      (RS) enzyme, a family of enzymes that use the reductive cleavage of a [4Fe-4S]
      cluster-bound SAM molecule to generate a 5'-deoxyadenosyl radical. This radical
      is then used to initiate an array of reactions that otherwise would be unlikely
      to occur. PqqE is a founding member of a subset family of RS enzymes that,
      additionally to the SAM [4Fe-4S] cluster, have a SPASM domain containing
      additional, auxiliary Fe-S clusters. Most radical SAM enzymes are highly
      sensitive to oxygen, which destroys their Fe-S clusters. This can pose several
      limitations when working with these enzymes, since most of the work has to be
      done under anaerobic conditions. Here, we summarize the methods developed in our
      lab for the expression and purification of PqqE. We also highlight the several
      methods we have used for the characterization of the enzyme.

PMID- 30097101
TI  - Methods for Studying the Radical SAM Enzymes in Diphthamide Biosynthesis.
AB  - Diphthamide is a unique posttranslational modification on translation elongation
      factor 2 (EF2) in archaea and eukaryotes. Biosynthesis of diphthamide was
      proposed to involve four steps. The first step is a CC bond forming reaction
      catalyzed by unique radical S-adenosylmethionine (SAM) enzymes. Classical radical
      SAM enzymes use SAM and [4Fe-4S] clusters to generate a 5'-deoxyadenynal radical
      and catalyze numerous reactions. Radical SAM enzymes in diphthamide biosynthesis
      cleave a different CS bond in SAM to generate a 3-amino-3-carboxypropyl radical
      and modify a histidine residue of substrate protein EF2. Here, we describe our
      investigations on these unique radical SAM enzymes, including the preparation,
      characterization, and activity assays we have developed.

PMID- 30097102
TI  - Guidelines for Determining the Structures of Radical SAM Enzyme-Catalyzed
      Modifications in the Biosynthesis of RiPP Natural Products.
AB  - Radical S-adenosylmethionine (RaS) enzymes catalyze some of the most fascinating
      transformations in Nature. With only ~100 of the >300,000 members studied to
      date, it is safe to assume that a plethora of new reactions and reaction
      mechanisms remain to be elucidated. It is by now relatively easy to spot RaS
      enzymes in microbial genomes. However, to determine the reactions that they carry
      out, detailed structural characterization of the product(s) is necessary, a
      process that still represents a significant roadblock in the study of RaS
      enzymes. We have recently combined natural products structural elucidation along
      with RaS enzymology to provide a proof of concept for how the confluence of these
      approaches can lead to the discovery of new natural products and RaS enzyme
      mediated transformations. Herein, we provide guidelines for expressing,
      purifying, and reconstituting a subclass of RaS enzymes that contain a so-called
      SPASM domain, as well as characterizing the reactions that they catalyze using a
      combination of HR/MSn and NMR investigations. Application of these approaches
      will aid in expanding the chemical and biosynthetic repertoire of RaS enzymes in
      the future.

PMID- 30097103
TI  - Identification of the Radical SAM Enzymes Involved in the Biosynthesis of
      Methanopterin and Coenzyme F420 in Methanogens.
AB  - Methanogenic archaea represent a source of unique and fascinating anaerobic
      biochemistry that includes the involvement of many radical S-adenosyl-l
      methionine (SAM) enzymes, some of which have well-established functions, while
      the majority have currently unknown or only partially understood functions. Here,
      we describe our strategy for the identification of the radical SAM enzyme that
      catalyzes the two methylation reactions in methanopterin biosynthesis in
      Methanocaldococcus jannaschii. Additionally, we describe the similar strategy
      carried out for the identification of the two radical SAM enzymes required for
      the biosynthesis of the 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F0) moiety of
      coenzyme F420 in M. jannaschii. This approach can be employed for future
      functional identification of radical SAM enzymes with currently unknown
      functions.

PMID- 30097105
TI  - Purification and Characterization of the Choline Trimethylamine-Lyase (CutC)
      Activating Protein CutD.
AB  - Anaerobic choline deamination catalyzed by the glycyl radical enzyme choline
      trimethylamine-lyase (CutC) has emerged as a major route for trimethylamine (TMA)
      production within anaerobic environments, including the human gut. The
      association of this microbial metabolite and its downstream products with
      diseases such as atherosclerosis and chronic kidney disease has driven the need
      for a better molecular understanding of TMA-generating enzymes. Our previous work
      has shown that generating the critical, glycine-centered radical species on CutC
      requires posttranslational modification by an S-adenosyl-l-methionine (SAM)
      dependent radical-activating protein (CutD) harboring an oxygen-sensitive [4Fe
      4S] cofactor. In this chapter, we describe our strategy to heterologously express
      and purify Desulfovibrio alaskensis G20 CutD in Escherichia coli and reconstitute
      its iron-sulfur center under anaerobic conditions. In addition, we present the
      methods we have developed to characterize the activity of CutD and utilize this
      enzyme in conjunction with purified CutC to gain an unprecedented insight into
      the anaerobic C-N cleavage of choline.

PMID- 30097106
TI  - QueE: A Radical SAM Enzyme Involved in the Biosynthesis of 7-Deazapurine
      Containing Natural Products.
AB  - 7-Carboxy-7-deazaguanine (CDG) is a common intermediate in the biosynthesis of 7
      deazapurine-containing natural products. The biosynthesis of CDG from GTP
      requires three enzymes: GTP cyclohydrolase I, 6-carboxy-5,6,7,8-tetrahydropterin
      (CPH4) synthase, and CDG synthase (QueE). QueE is a member of the radical S
      adenosyl-l-methionine (SAM) superfamily and catalyzes the SAM-dependent radical
      mediated ring contraction of CPH4 to generate CDG. This chapter focuses on
      methods to reconstitute the activity of QueE in vitro.

PMID- 30097104
TI  - Lessons From the Studies of a CC Bond Forming Radical SAM Enzyme in Molybdenum
      Cofactor Biosynthesis.
AB  - MoaA is one of the founding members of the radical S-adenosyl-L-methionine (SAM)
      superfamily, and together with the second enzyme, MoaC, catalyzes the
      construction of the pyranopterin backbone structure of the molybdenum cofactor
      (Moco). However, the exact functions of both MoaA and MoaC had remained ambiguous
      for more than 2 decades. Recently, their functions were finally elucidated
      through successful characterization of the MoaA product as 3',8-cyclo-7,8-dihydro
      GTP (3',8-cH2GTP), which was shown to be converted to cyclic pyranopterin
      monophosphate (cPMP) by MoaC. 3',8-cH2GTP was produced in a small quantity and
      was highly oxygen sensitive, which explains why this compound had previously
      eluded characterization. This chapter describes the methodologies for the
      characterization of MoaA, MoaC, and 3',8-cH2GTP, which together significantly
      altered the view of the mechanism of the pyranopterin backbone construction
      during the Moco biosynthesis. Through this chapter, we hope to share not only the
      protocols to study the first step of Moco biosynthesis but also the lessons we
      learned from the characterization of the chemically labile biosynthetic
      intermediate, which would be informative for the study of many other metabolic
      pathways and enzymes.

PMID- 30097107
TI  - Preface.

PMID- 30097108
TI  - Hydroalcoholic extract of Spartium junceum L. flowers inhibits growth and
      melanogenesis in B16-F10 cells by inducing senescence.
AB  - BACKGROUND: Ultraviolet light exposure generates, in human tissues, radical
      species, which represent the main cause of photo-aging, DNA damage and skin
      cancer onset. On the other hand, Mediterranean plants, being continuously
      subjected to high solar radiation levels, are naturally adapted to take on this
      type of abiotic stress, thanks to the production of antioxidant secondary
      metabolites. For these reasons, several plant extracts were documented to be
      excellent antineoplastic drugs. PURPOSE: We investigated the potential antitumor
      activity of the flower extract obtained by Spartium junceum L., a Mediterranean
      shrub, correlating it with the plant metabolic profile. STUDY DESIGN: After
      selecting the best extraction method to obtain as more secondary metabolites as
      possible from S. junceum flowers, we characterized the extract metabolic content.
      Then, by in vitro analyses, the antioxidant profile and the antineoplastic
      activity on B16-F10 murine melanoma cell of our extract were investigated.
      METHODS: Spectrophotometric assays, HPLC-DAD and GC-MS analyses provided us
      information about flower extract composition and antioxidant activity. MTT assay
      and Trypan Blue exclusion test were performed to assess the extract toxicity and
      the viability, after treatments, of B16-F10 cancer cells and of C2C12 murine
      myoblasts. In vitro experiments (i.e. cytofluorimetry, protein analysis and qPCR)
      allowed us to analyze the effect of the plant extract on B16-F10 cell redox
      state, melanogenesis and cell cycle. Senescence induction was investigated by
      using a specific kit. RESULTS: We observed that the hydroalcoholic extract of S.
      junceum flowers (HFE) strongly inhibited B16-F10 murine melanoma cell
      proliferation, while just a feeble effect was observed on C2C12 murine myoblasts.
      Moreover, we found that HFE exerted a pro-oxidant activity on melanoma cells,
      inhibited melanogenesis and caused cell cycle arrest in G2/M phase, inducing
      senescence. These anti-cancer properties of HFE could be related to the rich
      metabolic profile of the extract that we characterized by HPLC-DAD and GC-MS
      analyses. CONCLUSION: This evidence suggests that S. junceum phytocomplex can be
      used as a selective, nontoxic, economic and easily available anticancer drug.

PMID- 30097109
TI  - In vitro activity of collinin isolated from the leaves of Zanthoxylum
      schinifolium against multidrug- and extensively drug-resistant Mycobacterium
      tuberculosis.
AB  - BACKGROUND: Tuberculosis is a very serious infectious disease that threatens
      humanity, and the emergence of multidrug-resistant (MDR), extensively drug
      resistant (XDR) strains resistant to drugs suggests that new drug development is
      urgent. In order to develop new tuberculosis drug, we have conducted in vitro
      anti-tubercular tests on thousands of plant-derived substances and finally found
      collinin extracted from the leaves of Zanthoxylum schinifolium, which has an
      excellent anti-tuberculosis effect. PURPOSE: To isolate an anti-tubercular
      bioactive compound from the leaves of Z. schinifolium and evaluate whether this
      agent demonstrates any potential in vitro characteristics suitable for the
      development of future anti-tubercular drugs to treat MDR and XDR Mycobacterium
      tuberculosis. METHODS: The methanolic extracts of the leaves of Z. schinifolium
      were subjected to bioassay-guided fractionation against M. tuberculosis using a
      microbial cell viability assay. In addition, following cell cytotoxicity assay,
      an intracellular anti-mycobacterial activity of the most active anti-tubercular
      compound was investigated after it was purified. RESULTS: The active compound
      with anti-tubercular activity isolated from leaves of Z. schinifolium was
      identified as a collinin. The extracted collinin showed anti-tubercular activity
      against both drug-susceptible and -resistant strains of M. tuberculosis at 50%
      minimum inhibitory concentrations (MIC50s) of 3.13-6.25 ug/ml in culture broth
      and MIC50s of 6.25-12.50 ug/ml inside Raw264.7 and A549 cells. Collinin had no
      cytotoxicity against human lung pneumocytes up to a concentration of 100 ug/ml
      (selectivity index > 16-32). CONCLUSIONS: Collinin extracted from the leaves of
      Z. schinifolium significantly inhibits the growth of MDR and XDR M. tuberculosis
      in the culture broth. In addition, it also inhibits the growth of intracellular
      drug-susceptible and drug-resistant tuberculosis in Raw264.7 and A549 cells. To
      our knowledge, this is the first report on the in vitro anti-tubercular activity
      of collinin, and our data suggest collinin as a potential drug to treat drug
      resistant tuberculosis. Further studies are warranted to assess the in vivo
      efficacy and therapeutic potential of collinin.

PMID- 30097110
TI  - Grandiflorenic acid promotes death of promastigotes via apoptosis-like mechanism
      and affects amastigotes by increasing total iron bound capacity.
AB  - BACKGROUND: American tegumentary leishmaniasis (ATL) is a zoonotic disease caused
      by protozoa of the genus Leishmania. The high toxicity, high costs and resistance
      of some strains to current drugs has prompted the search for therapeutic
      alternatives for the management of this disease. Sphagneticola trilobata is a
      plant that has diterpenes as main constituents, including grandiflorenic acid
      (GFA) that has antiinflammatory, antiprotozoal, antibacterial and antinociceptive
      activity. PURPOSE: The aim of our study was to determine the effect of GFA on
      both the promastigotes and the amastigotes of Leishmania amazonensis. METHODS:
      Isolation by chromatographic methods and chemical identification of GFA, then
      evaluation of the in vitro leishmanicidal activity of this compound against
      Leishmania amazonensis promastigotes and L. amazonensis infected peritoneal
      Balb/c macrophages, as well its action and microbicide mechanisms. RESULTS: GFA
      treatment significantly inhibited the proliferation of promastigotes. This
      antiproliferative effect was accompanied by morphological changes in the parasite
      with 25 nM GFA. Afterwards, we investigated the mechanisms involved in the death
      of the protozoan; there was an increase in the production of reactive oxygen
      species (ROS), phosphatidylserine exposure, permeabilization of the plasma
      membrane and decreased mitochondrial depolarization. In addition, we observed
      that the treatment caused a reduction in the percentage of infected cells and the
      number of amastigotes per macrophage, without showing cytotoxicity in low doses
      to peritoneal macrophages and sheep erythrocytes. GFA increased IL-10 and total
      iron bound to transferrin in infected macrophages. Our results showed that GFA
      treatment acts on promastigote forms through an apoptosis-like mechanism and on
      intracellular amastigote forms, dependent of regulatory cytokine IL-10 modulation
      with increase in total iron bound to transferrin. CONCLUSION: GFA showed in vitro
      antileishmanial activity on L. amazonensis promastigotes forms and on L.
      amazonensis-infected macrophages.

PMID- 30097111
TI  - Antiproliferative effect and ultrastructural alterations induced by 5-O
      methylembelin on Trypanosoma cruzi.
AB  - BACKGROUND: Embelin (EMB), obtained from Oxalis erythrorhiza Gillies ex Hooker et
      Arnott (Oxalidaceae), was reported against Trypanosoma cruzi and Leishmania spp.
      Additionally, antiprotozoan activity against Plasmodium falciparum was reported
      for its methylated derivative (ME). PURPOSE: To evaluate the potential anti
      Trypanosoma cruzi activity of EMB, ME and 2,5-di-O-methylembelin (DME) and
      analyze the possible mechanism of action. STUDY DESIGN/METHODS: EMB was isolated
      by a chromatographic method from the air-dried ground whole plant. To evaluate
      the effects of methylation, ME and DME were synthesized and tested against T.
      cruzi epimastigotes and trypomastigotes. The most active compound ME was
      evaluated against amastigotes. Ultrastructural alterations, ROS generation and
      the effect on mitochondrial activity of ME were measured. RESULTS: Compounds
      inhibited the proliferation of epimastigotes. ME was also active against
      intracellular amastigotes. Mitochondrial alterations were observed by TEM.
      Additionally, ME modified the mitochondrial activity, and induced an increase in
      ROS levels. These evidences postulate the mitochondrion as a possible target of
      ME. CONCLUSION: ME inhibited amastigotes proliferation, thus being a potential
      lead compound for the treatment of Chagas' disease.

PMID- 30097113
TI  - Turmeric extract, with absorbable curcumin, has potent anti-metastatic effect in
      vitro and in vivo.
AB  - BACKGROUND: Curcumin, a well-studied component in turmeric, exhibits potent
      antitumor effects in colorectal cancer. Previous studies showed that turmerones
      raised the accumulation of curcumin inside colonic cells, and curcumin present in
      turmeric ethanolic extract had enhanced anti-tumor activities in mice. Metastasis
      accounts for more than 90% colorectal cancer deaths. However, the anti-metastatic
      effect of turmeric extract on colorectal cancer is still unknown. METHODS: In the
      present study, colony formation, scratch, transwell and Western blot were used to
      assess colony formation, motility, migration and underlying mechanisms in vitro,
      respectively. Anti-tumor and anti-metastatic effects in vivo were investigated
      using an orthotopic xenograft model. RESULTS: Turmeric extract exhibited
      cytotoxic effect, inhibited colony formation, decreased cell motility, migration
      and epithelial-mesenchymal transitions through regulating multiple pathways
      including cofilin, FAK/p-Src, AKT, Erk and STAT3 signaling pathways in murine
      colorectal cancer cells. Furthermore, turmeric extract at 200 mg/kg could
      decrease colon tumor burden and inhibit liver and lung metastasis in vivo.
      Treatment of turmeric extract enhanced immunity through T cell stimulation,
      changed tumor microenvironment, exerted anti-metastatic effects which were shown
      for the first time in pre-clinical colorectal cancer models. The decrease of
      immunity after FOLFOX treatment was also firstly demonstrated in mouse model.
      CONCLUSIONS: Turmeric extract was demonstrated for the first time for its anti
      tumor and anti-metastatic effects in both colorectal cancer cells and orthotopic
      mouse model through regulation of multiple targets. These findings strongly
      suggested the promising use of turmeric extract as chemopreventive or
      chemotherapeutic agent for colorectal cancer patients with metastasis.

PMID- 30097112
TI  - In silico and in vitro analysis of coumarin derivative induced anticancer effects
      by undergoing intrinsic pathway mediated apoptosis in human stomach cancer.
AB  - BACKGROUND: Coumarin plays a vital role in drug discovery process due to its
      diverse biologically active components. Recently, coumarin derivatives are paying
      attention to treat various diseases including cancer. The effect of coumarin
      derivatives on gastric cancer is not well established although gastric cancer
      being the fourth leading cancer. Therefore, we attempt to study the effect of
      styrene substituted biscoumarin (SSBC) to induce apoptosis and inhibit cancer
      proliferation using in silico and in vitro approaches. METHODS: We performed 3
      (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay to
      identify the anti-proliferative activity of SSBC in stomach cancer cell lines
      (AGS) and toxicity of the compared was also assessed using lung normal cell lines
      (L-132 and MRC-5). A docking study was carried out between anti-apoptotic protein
      (BCL2) and SSBC compound. Furthermore, we analyzed the drug likeliness by
      screening pharmacological properties (ADME) and biological activity of SSBC by
      performing spectrum prediction analysis (PASS). The apoptotic effect of SSBC in
      AGS cell lines were detected using flow cytometry (FACS), Hoechst staining and
      DAPI/PI staining. Later, the regulation of apoptotic pathway by SSBC was also
      confirmed by qRT-PCR and western blotting analysis. RESULTS: The inhibition
      concentration (IC50) of SSBC was assayed against AGS and lung normal cell lines
      (L-132 and MRC-5). The IC50 value of SSBC toward AGS, L-132 and MRC-5 was 4.56,
      268 and 285 MUg/ml, respectively. In silico analysis predicted SSBC could bind to
      the active site of BH3 domain of anti-apoptotic protein and thus resulted in
      apoptotic mediated cell death. ADME prediction of SSBC exhibit strong binding
      capacity of 99.08% and showed absorption rate about 95.57% in the intestine. In
      addition, biological activity of SSBC was also predicted using PASS program and
      we found SSBC exhibit high activity for various cancer related protein expression
      including apoptosis pathway proteins such as caspase 3 stimulant, apoptosis
      agonist. Furthermore, apoptosis of AGS was also assessed using Hoechst staining,
      DAPI/PI analysis, flow-cytometric analysis, qRT-PCR and western blot analysis.
      CONCLUSION: Our study denotes that SSBC could be very effective against AGS by
      inducing apoptosis through intrinsic pathway and recommended for in vivo and
      human trials.

PMID- 30097114
TI  - Botany, traditional use, phytochemistry, pharmacology, quality control, and
      authentication of Radix Gentianae Macrophyllae-A traditional medicine: A review.
AB  - BACKGROUND: Radix Gentianae Macrophyllae, commonly known as Qinjiao (in Chinese),
      is dried roots of medicinal plants that belong to Gentianaceae family and
      Gentiana genus. It has medically been used for the treatment of various diseases
      such as arthritis, stroke, facial paralysis, and scapulohumeral periarthritis in
      China since ancient times. PURPOSE: The aim of this paper is to provide a
      comprehensive and constructive overview of Qinjiao mainly containing Gentiana
      macrophylla Pall., Gentiana straminea Maxim., Gentiana crasicaulis Duthie ex
      Burk., and Gentiana daurica Fisch. in botany, traditional use, phytochemicals,
      pharmacology (biological activities and pharmacokinetics), quality control, and
      authentication according to the up-to-date data of available scientific
      literatures. MATERIALS AND METHODS: All information regarding these four plants
      was collected from various academic search engines for example Google, Google
      Scholar, Web of Science, SciFinder, Pubmed, CNKI, and Wanfang. Additional
      information was obtained from botanical books, Chinese classic texts, and medical
      monographs. RESULTS: So far 166 compounds have been isolated and identified from
      Qinjiao plants together with Gentiana tibetica King ex Hook. f., Gentiana
      siphonantha Maxim., Gentiana officinalis H. Smith, and Gentiana waltonii Burk.
      Their constituents are mainly classified into iridoid glycosides, triterpenes,
      flavones, sterols, benzene derivatives, etc. The pharmacological studies
      demonstrate that Qinjiao plants display a wide range of bioactivities e.g. anti
      inflammatory, anti-oxidant, hepato-protective, cardio- and neuro-protective,
      insecticidal, and anti-influenza effects. The conventional quality control is
      performed by determination of the concentration of some compounds, e.g.,
      gentiopicroside, or establishment of the fingerprint. In addition to seed
      propagation, tissue culture technology has been used to address the limited
      supplies and guarantee the sustainable development of Qinjiao in the experimental
      scale. CONCLUSIONS: Although the identification of compounds from Qinjiao and
      demonstration of medicinal uses in vitro and in vivo have been carried out,
      various other studies on these plants should deserve our more attention. More
      efforts should be concentrated on the underlying mechanisms of their beneficial
      bioactivities. The proper toxic evaluation is indispensable to guarantee the
      safety, efficacy, and eligibility for medical use. To sum up, the summarized
      achievements could highlight the importance of Qinjiao and provide a solid
      foundation for scientists not only to further exploit the therapeutic potentials,
      but also possibly develop novel drugs in the subsequent research.

PMID- 30097115
TI  - Stigmasterol upregulates immediate early genes and promotes neuronal
      cytoarchitecture in primary hippocampal neurons as revealed by transcriptome
      analysis.
AB  - BACKGROUND: The hippocampus is a vulnerable brain region that is implicated in
      learning and memory impairment by two pathophysiological features, that is,
      neurite regression and synaptic dysfunction, and stigmasterol (ST), a cholesterol
      equivalent phytosterol, is known to facilitate neuromodulatory effects. PURPOSE:
      To investigate the neuromodulatory effects of ST on the development of central
      nervous system neurons and the molecular bases of these effects in primary
      hippocampal neurons. METHODS: Rat embryonic (E18-19) brain neurons were cultured
      in the absence or presence of ST (75 uM). Neuritogenic activities of ST were
      evident by increases in various morphometric parameters. To identify underlying
      affected genes, total RNA was isolated on day in vitro 12 (DIV 12) and mRNA high
      throughput sequencing (mRNA-Seq) was performed. Affected key genes for neuronal
      development were identified using bioinformatics tools and their upregulations
      were confirmed by immunocytochemistry. RESULTS: Among the differentially
      expressed 17,337 RefSeq genes, 445 genes (up/down 293/157) passed the p-value <
      0.05 criterion, 52 genes (up/down; 37/13) had a p-value < 0.05 and a false
      discovery rate (FDR) q-value of < 0.2, and 24 genes (up/down; 20/4) passed the
      more stringent criterion of both p < 0.05 and q < 0.05. After applying a
      stringent FDR q-value cutoff of < 0.2, it was found ST induced many immediate
      early genes (IEGs), and that a major proportion of upregulated genes were related
      to central nervous system (CNS) development (neurite outgrowth or synaptic
      transmission). In a Venn diagram for CNS development Gene Ontologies (GOs) (i.e.,
      axon development, dendrite development, modulation of synaptic transmission),
      Reln emerged as a central player in these processes, and highly interconnected
      'hub' genes, including Dcx, Egr1, Ntrk2, and Slc24a2, were revealed by gene co
      expression networks. Finally, transcriptomic data was confirmed by
      immunocytochemistry of primary hippocampal neurons. CONCLUSION: The study
      indicates that ST upregulates genes for neuritogenesis and synaptogenesis, and
      suggests ST be viewed as a potential resource for improving brain functions.

PMID- 30097116
TI  - The effects of urolithins on the response of prostate cancer cells to non
      steroidal antiandrogen bicalutamide.
AB  - BACKGROUND: Urolithins are bioavailable products of gut microbiota metabolism of
      ellagitannins. Their biological activity includes anti-cancer effects. PURPOSE:
      The aim of this study was to explore the effects of urolithins on prostate cancer
      cells and activity of clinically used anti-androgen, bicalutamide. METHODS:
      Prostate cancer cells were treated with urolithin A, urolithin B, urolithin C or
      their combinations with bicalutamide. Cell proliferation was determined by DNA
      fluorescence with Hoechst 33258. The combination index method was used to examine
      interactions. Apoptosis and androgen receptor (AR) localization were analysed by
      flow cytometry. Prostate specific antigen (PSA) secretion was measured by ELISA.
      RESULTS: Urolithins inhibited proliferation of LNCaP prostate cancer cells. The
      mixtures of bicalutamide with uroA and uroB had additive anti-proliferative
      effect. All tested urolithins induced apoptosis of LNCaP cells. However, the
      combinations of bicalutamide with urolithin A and urolithin B had attenuated pro
      apoptotic activity. UroA and uroC decreased DHT-induced PSA secretion. In
      contrast, uroB impaired PSA lowering effect of bicalutamide. UroA, individually
      and in combination with bicalutamide, promoted cytoplasmic localization of AR.
      CONCLUSION: Urolithins might contribute to chemopreventive activity of
      ellagitannin rich preparations. Our results support use of ellagitannin rich
      preparations in prostate cancer chemoprevention, but advise caution in their
      potential use in complementary therapy of prostate cancer. The differences in
      activity profiles of urolithins indicate that possible health benefits and
      interactions will depend on the type of produced ellagitannins metabolite.

PMID- 30097117
TI  - Aqueous extracts of Paeonia suffruticosa modulates mitochondrial proteostasis by
      reactive oxygen species-induced endoplasmic reticulum stress in pancreatic cancer
      cells.
AB  - BACKGROUND: Pancreatic cancer (PC) remains the leading cause of cancer mortality,
      with limited therapeutic targets, and alterations in endoplasmic reticulum (ER)
      related proteostasis may be a potential target for therapy. The root bark of
      Paeonia suffruticosa has been shown to inhibit cancer growth and metastasis,
      although its impact on PC is unknown. PURPOSE: To ascertain the anti-cancer
      effects of P. suffruticosa on oncogenic functions of PC and determine the
      detailed molecular mechanisms. STUDY DESIGN: Efficacy assessment of extracts, in
      vitro using PC cells as a model system and in vivo in mouse xenograft tumors.
      METHODS: P. suffruticosa aqueous extracts (PS) were prepared and assessed using
      liquid chromatography-tandem mass spectrometry. Cell viability, proteins, and
      cell components were measured using MTT assay, western blotting, and
      immunofluorescence. Cell apoptosis, cell cycle, and migration were assessed using
      colorimetric assays, fluorescence activated cell sorting, and transwell
      migration. Reactive oxygen species (ROS) were evaluated with a commercial 2'-7'
      dichlorofluorescin diacetate kit. For the xenograft model, AsPC1 cells were
      inoculated subcutaneously into immunocompromised mice and PS (oral) was
      administered over 3 weeks with or without gemcitabine (GEM, intraperitoneal), a
      first-line advanced/metastatic PC therapy. RESULTS: PS stimulated ER stress and
      affected mitochondrial membrane potential to increase autophagosome numbers and
      block their degradation, followed by autophagy induction and finally cell
      apoptosis. Additionally, PS-mediated proteostasis impairment resulted in altered
      dynamics of the actin cytoskeleton, cell motility impairment, and cell cycle
      progression inhibition. Conversely, a ROS scavenger partially reversed PS
      mediated degradation of peptidyl-prolyl cis-trans isomerase B (PPIB), an ER
      protein important for protein folding, suggesting that ROS generation by PS may
      be the upstream of PS-triggering of mitophagy and final cell apoptosis.
      Nevertheless, oral administration of PS, alone or in combination with GEM,
      delayed tumor growth in a xenograft model without affecting body weight.
      CONCLUSION: These findings indicate that PS may constitute a potential new
      alternative or complementary medicine for PC.

PMID- 30097118
TI  - Hypericin inhibits hepatitis C virus replication via deacetylation and down
      regulation of heme oxygenase-1.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a globally prevalent pathogen and a
      leading cause of death and morbidity. Traditional therapy with pegylated
      interferon-<alpha> and ribavirin has had only limited success, with some adverse
      effects. Direct-acting antivirals (DAAs) are effective in suppressing HCV
      replication, but are expensive. PURPOSE: Hypericin has been reported to be a good
      antiviral agent for inhibiting HCV replication, however, little is known about
      its mechanisms of action. The aim of this study is to elucidate the mode of
      action of hypericin in Ava5 human hepatoma cell line (Huh7 derivative) harboring
      HCV subgenomic replicon RNA. METHODS: To determine the non-structure protein 5A
      (NS5A) mRNA and NS3 protein expression levels, real-time PCR and Western blot
      analysis were performed, respectively. To investigate how hypericin inhibits HCV
      replication, 5-aza-2'-deoxycytidine (5-Aza-dC) and chidamide were used for
      determining histone modification. Furthermore, shRNA was applied to confirm the
      role of heme oxygenase (HO-1) in HCV repression. RESULTS: Hypericin in experiment
      were tested and showed no cytotoxicity. Hypericin reduced HO-1 and NS5A in a time
      and dose- dependent manner. Chidamide, but not 5-Aza-dc, restored hypericin
      induced reduction in HCV NS3 expression and reversed HO-1 expression in Ava5
      cells. LY294002 inhibited HCV replication via HO-1 down-regulation. Constitutive
      expressed p-AKT was not involved in hypericin-induced reduction in HCV
      replication. In addition, shHO-1 inhibited HCV replication. CONCLUSION: In
      conclusion, hypericin inhibits HCV replication via down-regulation of HO-1
      expression and deacetylation.

PMID- 30097119
TI  - Tetrandrine enhances the antifungal activity of fluconazole in a murine model of
      disseminated candidiasis.
AB  - BACKGROUND: Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from
      the Chinese medicinal herb Stephaniae tetrandrae, has a long history in Chinese
      clinical applications as an anti-inflammatory or anti-arrhythmic agent in the
      treatment of diverse diseases. In our previous study, TET exhibited the
      synergisitic action on azoles against pathogenic fungi. PURPOSE: In the current
      study, we examined whether TET can enhance the antifungal activity of FLC against
      disseminated candidiasis in mice. METHODS: BALB/c mice were inoculated
      intravenously with FLC-sensitive or FLC-resistant strains of Candida albicans,
      randomized and treated intraperitoneally with different doses of TET and/or FLC
      daily for 7 days. The treatment effectiveness, fungal burdens and the levels of
      the IFN-gamma, IL-10, TGF-beta1 and IL-17A are determined in serum by ELISA and
      in the kidney by Real-time RT-PCR methods. RESULTS: We found that treatment with
      45, 30 and 15 mg/kg of TET, enhanced the antifungal activities of a sub-critical
      dose (0.4 or 5 mg/kg) and minimal dose (0.8 or 10 mg/kg) of FLC against FLC
      sensitive and FLC-resistant (respectively) infected mice. In the resistant
      strains the resistance mechanisms included MDR1 overexpression-and CDR1/CDR2
      overexpression. Furthermore, when animals were treated with a sub-high dose (1.6
      3.2 and 20-30 mg/kg) of FLC in the presence of fixed amounts of TET at 45, 30 and
      15 mg/kg, the therapeutic doses of FLC could be substantially reduced in all
      strains tested. The findings in infected animal are consistent with the
      conclusion that TET exerts a synergistic effect on FLC against C. albicans by
      fractional inhibitory concentration index (FICI) and time-killing test in vitro.
      CONCLUSION: In summary, our data indicate that TET will enhance the antifungal
      activity of FLC against C. albicans infection in disseminated mice model.

PMID- 30097120
TI  - Astragalus Root dry extract restores connexin43 expression by targeting miR-1 in
      viral myocarditis.
AB  - BACKGROUND: Viral myocarditis is defined as viral infection of myocardial tissue
      leading to impaired heart function and heart failure. Accumulating evidences have
      shown that arrhythmia is one of important complicating diseases of viral
      myocarditis causing increased mortality and morbidity. There are no effective
      treatment for the viral infection and complicating arrhythmia. PURPOSE: This
      study investigated the effect and mechanism of Astragalus Root dry extract (ARDE)
      on arrhythmia induced by CVB3 in mice. METHODS: The mice and HL-1 cells were
      treated with CVB3 and ARDE. Reciprocal regulation of Cx43 and miR-1 were observed
      in the CVB3 infected mouse myocardium and culture HL-1 cells. RESULTS: CVB3 IP
      injection increased immune cell infiltration in mouse left ventricle and caused
      irregular arrhythmia. ARDE treatment prevented the increase of immune cell
      infiltration and arrhythmia. Overexpression of miR-1 significantly inhibited both
      endogenous Cx43 expression and Cx43 3'UTR luciferase activity in HL-1 cells.
      Mutation of census binding site of +1586-1593 bp not +465-472 bp in Cx43 3'UTR
      luciferase resulted in abolishment of miR-1 inhibitory effects in HL-1 cells.
      Loss-of- function of miR-1 restored CVB3-induced Cx43 expression reduction in
      cultured HL-1 cells. The presence of ARDE attenuated the augmented miR-1 induced
      by CVB3 infection in vivo and in vitro. CONCLUSION: This study identified that
      CVB3 infection reduced Cx43 expression by elevating miR-1 level in mouse viral
      myocarditis. For the first time, ARDE was shown to prevent arrhythmia, and rescue
      CVB3-induced endogenous Cx43 expression by regulating miR-1 level.

PMID- 30097121
TI  - Urtica dioica L. leaf extract modulates blood pressure and oxidative stress in
      spontaneously hypertensive rats.
AB  - BACKGROUND: Urtica dioica L. (Stinging nettle) has been used for centuries for
      the treatment of numerous health issues. PURPOSE: This study investigates the
      antioxidant capacity and the most abundant phenolic compounds of Urtica dioica L.
      leaf extract (UE), and its antihypertensive and antioxidative effects in vivo.
      STUDY DESIGN: Spontaneously hypertensive rats were supplemented with 10, 50, and
      200 mg/kg/day of UE and 10 mg/kg/day of losartan during 4-week period. METHODS:
      In this study, HPLC analysis of UE was performed, as well as the determination of
      antioxidant capacity, superoxide radical scavenging activity, and metal chelating
      ability. Hemodynamic parameters were measured directly in anesthetized rats.
      Also, antioxidant enzyme activity and concentration in erythrocytes were
      determined, as well as systemic oxidative stress and plasma antioxidant status.
      RESULTS: UE showed higher ferric reducing antioxidant power and Trolox equivalent
      antioxidant capacity than BHT, but lower than vitamin C. Furthermore, UE showed
      good metal chelating ability, but weak superoxide radical scavenging activity.
      All three tested UE doses managed to reduce systolic and diastolic blood
      pressure, as well as cardiac index, and to improve the antioxidative defense by
      increasing the activity of superoxide dismutase and catalase, without changing
      the concentration of the enzymes. Moreover, UE supplementation increased plasma
      antioxidant capacity and reduced systemic oxidative stress. CONCLUSION: Chronic
      UE dietary supplementation had beneficial effects in the experimental model of
      essential hypertension.

PMID- 30097122
TI  - Eupatilin ameliorates dextran sulphate sodium-induced colitis in mice partly
      through promoting AMPK activation.
AB  - BACKGROUND: Despite the higher morbidity of ulcerative colitis (UC), available
      treatments remain unsatisfactory in recent years. A natural flavone eupatilin
      (Eup) is known to inhibit the intestinal contraction. PURPOSE: The protective
      role of Eup in intestinal inflammation remains unclear. This study attempted to
      determine the bioactivity of Eup against colitis and clarify the mechanism of
      action. STUDY DESIGN: The in vitro effects of Eup on lipopolysaccharide-induced
      human THP-M macrophage activation and tumour necrosis factor-alpha (TNF-alpha)
      damaged intestinal epithelial (NCM460) cells were explored to clarify its
      potential protective effects. Then, the alleviative efficacy of Eup was
      established in dextran sodium sulphate (DSS)-induced mice colitis. METHODS:
      Pathological diagnosis, immunohistochemical staining, and reverse transcriptase
      PCR analysis as well as western blot analysis were employed in the current study.
      RESULTS: Eup clearly inhibited inflammatory responses in LPS-stimulated
      macrophages. Eup also clearly stabilized colonic epithelia by down-regulating
      overexpression of tight junction proteins and NADPH oxidases 4 (NOX4), and by
      promoting AMP-activated protein kinase (AMPK) activation in TNF-alpha-stimulated
      NCM460 cells. In addition, in vivo study demonstrated that Eup treatment clearly
      ameliorated the symptoms and pathologic changes of colitis mice. The therapeutic
      effect of Eup was found to be reduced when compound C (an AMPK pharmacological
      inhibitor) was given to mice. CONCLUSION: The study successfully demonstrated
      that Eup ameliorated DSS-induced mice colitis by suppressing inflammation and
      maintaining the integrity of the intestinal epithelial barrier via AMPK
      activation. The results provide valuable guidance for using Eup in UC treatment.

PMID- 30097124
TI  - Nigella sativa fixed oil as alternative treatment in management of pain in
      arthritis rheumatoid.
AB  - BACKGROUND: N. sativa seeds is the source of fixed oil, which contain fatty acids
      and thymoquinone. N. sativa fixed oil topically or orally is used traditionally
      for management of pain in back, joints, musculoskeletal organs and arthritis
      rheumatoid. PURPOSE: The aim of this review article was to evaluate the potential
      effects of N. sativa fixed oil in pain and inflammation, especially in arthritis
      rheumatoid. METHODS: All information was extracted from accessible and
      inaccessible sources (books, electronic sources, thesis and etc.). RESULTS: The
      results of our investigation showed N. sativa fixed oil, especially thymoquinone
      content had valuable anti-inflammatory and analgesic effects via different
      pathways. The efficacy of thymoquinone as potential treatment was confirmed in
      different animal model of arthritis and the clinical studies confirmed the oral
      (n = 4) and topical use (n = 1) of N. sativa fixed oil without adverse effects in
      patients suffering from arthritis rheumatoid. CONCLUSION: The larger multicenter
      clinical trials for comparing the efficacy of topical, oral administrations and
      current treatment may help to understand better the efficacy of valuable fixed
      oil.

PMID- 30097123
TI  - Bioactive compound 1,8-Cineole selectively induces G2/M arrest in A431 cells
      through the upregulation of the p53 signaling pathway and molecular docking
      studies.
AB  - BACKGROUND: Callistemon citrinus has been traditionally known for its medicinal
      property. Recently, our research group identified 1,8-Cineole, as one of the
      predominant compound present in the hexane extract (HE-C), whose leaves have
      potent anticancer activity. HYPOTHESIS/PURPOSE: The present study was designed to
      isolate 1,8-Cineole from Callistemon citrinus plant and to determine their role
      in anticancer effects in in vitro using skin carcinoma cells. Moreover, the
      molecular mechanism of apoptosis and molecular docking studies were also
      investigated. STUDY DESIGN/METHODS: In vitro cytotoxicity test was performed with
      HE-C fractionates 1F, 2F, and 3F against A431 and HaCaT cell lines. MTT and AB
      assay demonstrated that 1F was toxic to cancer cells with no adverse effect to
      non-malignant cells and it was subjected to 1H NMR, 13C NMR spectroscopy and
      further characterized by FTIR and GC-MS analysis. On the basis of spectroscopic
      data, the metabolite was confirmed as 1,8-Cineole. RESULTS: Based on the
      cytotoxicity results, the well-characterized metabolite 1,8-Cineole was
      investigated upon to understand the mechanism that caused cancer cell death. In
      this process, the changes in mitochondrial membrane potential (DeltaPsim) were
      confirmed by Rh-123/DAPI staining; the ultra structure was observed by TEM and
      quantified by flow cytometric analysis. These results proved that the compound
      effectively induced the apoptosis and G2/M phase arrest in A431 cells by
      increasing the expression of p53 and that it was monitored by FACS. Further, the
      expression of apoptotic proteins, such as Bax/Bcl-2, Cyt-c, caspase-9, and
      caspase-3 was confirmed by western blot. The molecular docking simulations
      predicted the hydrophobic interaction between 1,8-cineole with Bcl-2 and PARP1
      receptor. CONCLUSIONS: 1,8-Cineole is a potential candidate for skin carcinoma,
      which is possible by regulating the p53 apoptotic signaling pathway.

PMID- 30097126
TI  - Wnt/beta-catenin signaling pathway is involved in regulating the migration by an
      effective natural compound brucine in LoVo cells.
AB  - BACKGROUND: Colorectal cancer remains the third most common malignancies and
      migration is one of the main factors for its high mortality rate. Brucine, a
      natural plant alkaloid, has been proved to possess a variety of pharmacological
      functions including anti-tumor activities. PURPOSE: The aim of this study was to
      investigate the inhibitory effect of brucine on the colorectal cancer and the
      underlying mechanism. METHODS: In this study, colony formation assay and
      transwell assay were used to investigate the effect of brucine on LoVo cells
      viability and migration. Immunofluorescence assay, western blot assay and Gelatin
      zymography assay were used to study the mechanism of brucine. Xenograft model in
      nude mice was induced to investigate the in vivo effect of brucine on LoVo cells.
      RESULTS: Brucine could significantly decrease the viability, inhibit the colony
      formation and induce the apoptosis of LoVo cells. Brucine could also suppress the
      migration of LoVo cells in a dose-dependent manner. Western blot analysis
      elucidated that the inhibition of migration was associated with the decreasing
      expression of matrix metalloproteinases including MMP2, MMP3 and MMP9. Moreover,
      we found that treatment of brucine could downregulate the expression of Frizzled
      8, Wnt5a, APC and GSNK1A1, and increase the expression of AXIN1. Meanwhile,
      brucine also decreased the phosphorylation level of LRP5/6 and GSK3beta, and
      increased the level of p-beta-catenin. Xenografted model in nude mice study also
      revealed that oral administration of brucine could inhibit the growth and
      migration of LoVo cells by activating the expression of AXIN1 and p-beta-catenin.
      CONCLUSION: Brucine could suppress the migration of the colorectal cancer in
      vitro and in vivo and the effect was associated with the inhibition of the
      Wnt/beta-catenin signaling pathway.

PMID- 30097125
TI  - Total sesquiterpene lactones isolated from Inula helenium L. attenuates 2,4
      dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.
AB  - BACKGROUND: Inula helenium L. is an herb whose anti-inflammatory properties are
      attributed to its active components, the sesquiterpene lactones (SLs). Our
      previous study demonstrated that the total sesquiterpene lactones isolated from
      Inula helenium L. (TSL-IHL), consisting mainly of alantolactone (AL) and
      isoalantolactone (IAL), may have potential in the prevention and treatment of
      rheumatoid arthritis (RA). However, the effect of TSL-IHL on atopic dermatitis
      (AD) has not been studied yet. AIM OF THE STUDY: The present study evaluates the
      potential of TSL-IHL as a treatment for AD. METHODS/STUDY DESIGNS: The effects of
      TSL-IHL on the expression of inflammatory genes and the activation of NF-kappaB
      signaling pathway in HaCat cells were examined by quantitative real-time PCR and
      western blotting, respectively, and compared with those of AL and IAL. The
      protective effect of TSL-IHL against AD was tested in a mouse model induced by
      2,4-dinitrochlorobenzene (DNCB), in which AD-like skin lesions were induced in
      ICR mice by sensitizing once with 100 ul of 7% DNCB painted on their shaved back
      skin and then challenging with 20 ul of 0.2% DNCB five times on their right ears
      at 3 day intervals starting on day 5 post-sensitization. RESULTS: TSL-IHL, as
      well as AL and IAL, could all inhibit TNF-alpha-induced activation of NF-kappaB
      and the expression of TNF-alpha, IL-1, and IL-4 in HaCat cells in a dose
      dependent manner in the range of 0.6-2.4 ug/ml. The topical application of TSL
      IHL (1% W/W in emollient cream) attenuated DNCB-induced dermatitis severity and
      right ear swelling. The serum levels of IgE, TNF-alpha and IFN-gamma in TSL-IHL
      treated mice were reduced by 81.39%, 89.69%, and 87.85%, respectively, while the
      mRNA levels of IL-4, IL-5 and IL-13, in the back-skin lesions of TSL-IHL-treated
      mice were reduced by 39.21%, 40.62% and 48.12%, respectively, compared with the
      untreated controls. Histopathological examination showed that TSL-IHL treatment
      reduced epidermis/dermis thickening and dermal inflammatory infiltration in both
      ear and back skins. CONCLUSIONS: We suggest that TSL-IHL inhibited the
      development of AD-like skin symptoms by regulating cytokine expression and may be
      an effective alternative therapy for AD.

PMID- 30097128
TI  - The associated features of multiple somatic symptom complexes.
AB  - OBJECTIVE: To assess whether two or more functional somatic symptom complexes
      (SSCs) showed stronger association with psychosocial correlates than single or no
      SSC after adjustment for depression/anxiety and general medical disorders.
      METHODS: In a population-based sample we identified, by standardised
      questionnaire, participants with chronic widespread pain, chronic fatigue and
      irritable bowel syndrome, excluding those with a medical cause for pain/fatigue.
      We compared psychosocial variables in three groups: multiple (>1), single or no
      FSS, adjusting for depression/anxiety and general medical disorders using ordinal
      logistic regression. We evaluated whether multiple SSCs predicted health status 1
      year later using multiple regression to adjust for confounders. RESULTS: Of 1443
      participants (58.0% response) medical records were examined in 990: 4.4% (n = 44)
      had 2 or 3 symptom complexes, 16.2% a single symptom complex. Many psychosocial
      adversities were significantly associated with number of SSCs in the expected
      direction but, for many, statistical significance was lost after adjustment for
      depression/anxiety and medical illness. Somatic symptoms, health anxiety,
      impairment and number of prior doctor visits remained significantly associated.
      Impaired health status 1 year later was predicted by multiple somatic symptom
      complexes even after adjustment for depression, anxiety, medical disorders and
      number of symptoms. CONCLUSIONS: Depression, anxiety, medical illness and health
      anxiety, demonstrated an exposure-response relationship with number of somatic
      symptom complexes. These may be core features of all Functional Somatic Syndromes
      and may explain why number of somatic symptom complexes predicted subsequent
      health status. These features merit inclusion in prospective studies to ascertain
      causal relationships.

PMID- 30097127
TI  - Investigation of ovatodiolide, a macrocyclic diterpenoid, as a potential
      inhibitor of oral cancer stem-like cells properties via the inhibition of the
      JAK2/STAT3/JARID1B signal circuit.
AB  - BACKGROUND: The cancer stem cells (CSCs) have been shown to play key roles in the
      oral cancer initiation, distant metastasis, the development of chemoresistance
      and recurrence after treatment. Therefore, the inhibition of oral CSCs has been
      the target for therapeutic development. PURPOSE: In this study, we investigated
      the anti-CSCs potential of Ovatodiolide (Ova), a diterpenoid isolate of
      Anisomeles indica, in vitro and in vivo. METHODS: Oral CSCs were treated with
      Ova, and the expression of pluripotency factors Oct4, Sox-2, and Nanog were
      evaluated by western blot. Effect of Ova on self-renewal capacity and
      clonogenicity were assessed with the sphere formation and clonogenic assay in
      CSCs model derived from oral cancer cell. The effect of Ova was also investigated
      in a mouse xenograft model obtained by injecting nude mice with oral CSCs cells.
      RESULTS: We demonstrated that Ova significantly and dose-dependently suppressed
      oral cancer cell viability and colony formation; Ova markedly inhibited the ALDH1
      activities and reduced the CD44high/ALDHrich cell sub-population. Additionally,
      Ova suppressed orosphere formation by down-regulating CD133, Klf4, Oct4A, Nanog
      and JARID1B expression. Furthermore, Ova-mediated anti-cancer effects were
      associated with the dose-dependent reduction in the expression levels of STAT3, p
      STAT3, pJAK2, pAKT and pERK1/2 protein. Moreover, Ova synergistically enhanced
      the anticancer effect of cisplatin against the SAS, FaDu, HSC-3 and TW2.6
      orospheres. Ova significantly attenuated the tumor-initiating potential of
      orosphere in mouse xegnograft model. CONCLUSION: These results demonstrate that
      Ova effectively suppressed oral tumorigenesis and stemness properties via
      JAK2/STAT3 signaling. Ova may be considered for future clinical usage.

PMID- 30097129
TI  - Acute stress and subsequent health outcomes: A systematic review.
AB  - OBJECTIVE: To systematically review the relationship between acute posttraumatic
      stress symptoms (<1 month) and subsequent physical and mental health outcomes
      other than posttraumatic stress disorder (PTSD). METHODS: A systematic search of
      electronic databases (PubMed, PsycINFO, CINAHL, and Web of Science) was conducted
      to identify longitudinal studies examining the link between acute posttraumatic
      stress and physical and mental health. Inclusion criteria required assessment of
      acute posttraumatic stress (<1 month post-event) and at least one follow-up
      assessment of a physical or mental health outcome (not PTSD). RESULTS: 1,051
      articles were screened; 22 met inclusion criteria. Fourteen studies examined
      physical health outcomes and 12 examined non-PTSD mental health outcomes. Early
      psychological responses to trauma were associated with a variety of short- (<1
      year) and long- (>=1 year) term physical and mental health outcomes. Physical
      health outcomes included poor general physical health, increased pain and
      disability, lower quality of life, and higher risk of all-cause mortality.
      Significant psychological outcomes included more cumulative psychiatric
      disorders, depression, and anxiety. Significant psychosocial outcomes included
      increased family conflict. CONCLUSIONS: Methodologically rigorous longitudinal
      studies support the utility of measuring acute psychological responses to
      traumatic events as they may be an important marker of preventable trauma-related
      morbidity and mortality that warrants long-term monitoring and/or early
      intervention.

PMID- 30097130
TI  - Pain as a symbol in the patient context.

PMID- 30097131
TI  - Early risk factors for depression, anxiety and post-traumatic distress after
      hospital admission for unintentional injury: Multicentre cohort study.
AB  - OBJECTIVE: To quantify psychological morbidity and identify baseline factors
      associated with depression, anxiety and post-traumatic distress symptoms up to 12
      months post-injury. METHODS: Multicentre cohort study of 668 adults, aged 16 to
      70, admitted to 4 UK NHS hospital trusts. Data on injury, socio-demographic
      characteristics and health status was collected at recruitment. Depression,
      anxiety and post-traumatic distress were measured at 1, 2, 4 and 12 months post
      injury. Multilevel linear regression assessed associations between patient and
      injury characteristics and psychological outcomes over 12 months follow-up.
      RESULTS: Depression, anxiety and post-traumatic distress scores were highest 1
      month post-injury, and remained above baseline at 2, 4 and 12 months post-injury.
      Moderate or severe injuries, previous psychiatric diagnoses, higher pre-injury
      depression and anxiety scores, middle age (45-64 years), greater deprivation and
      lower pre-injury quality of life (QoL) were associated with higher depression
      scores post-injury. Previous psychiatric diagnoses, higher pre-injury depression
      and anxiety scores, middle age, greater deprivation and lower pre-injury QoL were
      associated with higher anxiety scores post-injury. Traffic injuries or injuries
      from being struck by objects, multiple injures (>=3), being female, previous
      psychiatric diagnoses, higher pre-injury anxiety scores and greater deprivation
      were associated with higher post-traumatic distress scores post-injury.
      CONCLUSION: A range of risk factors, identifiable shortly after injury, are
      associated with psychological morbidity occurring up to 12 months post-injury in
      a general trauma population. Further research is required to explore the utility
      of these, and other risk factors in predicting psychological morbidity on an
      individual patient basis.

PMID- 30097132
TI  - Depression and psychological distress in patients with chronic renal failure:
      Prevalence and associated factors in a rural district in Sri Lanka.
AB  - OBJECTIVE: Chronic Kidney Disease (CKD) is known to adversely affect mental
      health. The study was aimed at estimating the prevalence of depression and
      psychological distress and the associated factors among CKD patients living in
      Anuradhapura, a rural district in Sri Lanka. METHOD: A community-based, cross
      sectional study included a representative sample of 1174 CKD patients, drawn
      proportionately from all registered patients in all 19 Medical Officer of Health
      areas in the district of Anuradhapura. Trained paramedical staff visited the
      households and administered the locally validated Centre for Epidemiologic
      Studies Depression Scale and General Health Questionnaire-12 to screen for
      depression and psychological distress. Information related to associated factors
      was obtained through an interviewer-administered questionnaire. RESULTS: A total
      of 1118 CKD patients participated, with a response rate of 95.2%. The mean age
      was 58.3 (SD 10.8) years. 62.7% of participants were males. The majority of
      participants was in CKD stage 4 (58.3%). The screening revealed that 75.0% (95%
      CI 72.5-77.5) of participants were psychologically distressed while 65.2% (95%CI
      62.4-68.0) were found to be depressed. Multiple logistic regression analysis
      revealed advanced age, unemployment and poor health related quality of life
      contributed significantly to both depression and psychological distress.
      CONCLUSION: Depression and psychological distress were significant in this
      community. Policymakers should consider the likely high prevalence of
      psychological distress and depression among CKD patients as well as the need for
      specific mental health services to confirm diagnosis and initiate effective
      management. Identified associated factors should be used to identify targeted
      preventative interventions.

PMID- 30097133
TI  - Cognitive behavioural therapy for anxiety disorders in Parkinson's disease:
      Design of a randomised controlled trial to assess clinical effectiveness and
      changes in cerebral connectivity.
AB  - BACKGROUND: Anxiety disorders occur in up to 35% of patients with Parkinson's
      disease (PD) and have a negative effect on motor symptoms and quality of life. To
      date, no clinical trials specifically targeting anxiety in PD patients have been
      published. OBJECTIVE: To describe the rationale and methodology of a randomised
      controlled trial (RCT) that aims to study the clinical effectiveness, alterations
      in brain circuitry, and cost-effectiveness of cognitive behavioural therapy (CBT)
      for anxiety in PD. METHODS: This study is a prospective, two-centre RCT in which
      sixty PD patients with anxiety will be randomised to CBT treatment and clinical
      monitoring (intervention group) or to clinical monitoring only (control group).
      The CBT module used in this study was specifically developed to address symptoms
      of anxiety in PD patients. Participants will undergo standardised clinical,
      cognitive and behavioural assessment at baseline and at 2 follow-up measurements,
      as well as resting-state fMRI and DTI scanning before and after the intervention.
      The primary outcome measure is changes in severity of anxiety symptoms. Secondary
      outcome measures involve long-term changes in anxiety symptoms, changes in
      functional and structural connectivity between limbic and frontal cortices, and
      cost-effectiveness of the treatment. The study is registered at the
      ClinicalTrials.gov database under registration number NCT02648737. CONCLUSION:
      This study is the first that evaluates both the clinical effectiveness, cost
      effectiveness, as well as the biological impact of CBT for anxiety in PD patients
      that, if proven effective, will hopefully contribute to a better and evidence
      based approach for these non-motor symptoms.

PMID- 30097134
TI  - Impaired mental health and low-grade inflammation among fatigued bereaved
      individuals.
AB  - BACKGROUND: Fatigue is a common symptom in stressed individuals. Bereavement is a
      major life event that has been associated with impaired mental health. Little
      research has investigated the prevalence of fatigue and its inflammatory
      correlates in bereaved individuals. OBJECTIVES: To assess fatigue prevalence and
      its relationship with mental health outcomes and markers of inflammation, as
      indexed by C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis
      factor alpha (TNF-alpha) in bereaved individuals. METHODS: Seventy-eight-bereaved
      adults were examined for fatigue (SF-36 energy/vitality scale), perceived stress
      (PSS), depression (CES-D), sleep quality (PSQI), pain (SF-36 pain scale), and
      general health (SF-36 general), and their serum levels of CRP, IL-6 and TNF-alpha
      were measured. Group differences between fatigued versus non-fatigued individuals
      were estimated using analysis of covariance (ANCOVA), with adjustment for body
      mass index (BMI). RESULTS: Fatigued bereaved individuals (33%; SF-36
      energy/vitality score 0-45) had significantly higher CRP levels (p < .05) as
      compared to non-fatigued bereaved individuals and reported higher levels of pain
      (p < .001), greater stress (p < .001), depression (p < .001), and sleeping
      problems (p < .001), as well as poorer social functioning (p < .001) and general
      health (p < .001) than those in the non-fatigued group. No group differences were
      found for IL-6 and TNF-alpha. CONCLUSIONS: Fatigued bereaved individuals showed
      elevated systemic inflammation as measured by CRP in comparison to non-fatigued
      bereaved individuals. They were also more likely to report mental health problems
      that co-occur with fatigue in the context of immune activation. Continued
      research is needed to help clarify the involvement of inflammatory markers in the
      development of fatigue in a larger sample of bereaved adults.

PMID- 30097135
TI  - Benefits of an on-line migraine education video for patients with co-occurring
      migraine and depression.
AB  - OBJECTIVE: To evaluate effects of an online, hour-long migraine education and
      management education program on health outcomes in people with migraine
      experiencing significant depressive symptoms. METHODS: Eligible individuals in
      the community with comorbid migraine and depressive symptoms (n = 95)
      participated in the 12-week study. Participants completed self-report
      questionnaires examining general functioning, headache-specific disability,
      migraine frequency, pain, and depressive symptoms, before, and at 2, 6, and 12
      weeks following the migraine education and management program. Primary analyses
      evaluated change over time in each outcome, using individual linear growth curve
      models. RESULTS: After watching the migraine education and management video,
      there were significant effects of time (across all time points) for average pain
      level in the past 30 days (b = -0.20, p < .001), most intense pain level in the
      past 30 days (b = -0.33, p < .001) depression (Patient Health Questionnaire-8; b
      = -0.28, p = .002), and headache-specific disability (Headache Disability
      Inventory; b = -1.32, p < .001), such that each of these outcomes improved
      linearly over time. CONCLUSIONS: A brief, online educational video is practical
      and effective and can lead to enhanced migraine knowledge and self-management
      skills and lessen the burden of migraine and concurrent depressive symptoms.

PMID- 30097136
TI  - Depressive symptoms and comorbid problems in pregnancy - results from a
      population based study.
AB  - OBJECTIVE: To estimate the prevalence of antenatal depressive symptoms, identify
      relevant risk factors, and assess comorbid mental health problems, among pregnant
      women enrolled in a population based study. METHODS: This was a secondary
      analysis of data collected from 1916 pregnant women who participated in the
      TRansgenerational Assessment of Children's Environmental Risk (TRACER) study in
      Kuwait, and had answered the Baseline Questionnaire and completed the Edinburgh
      Depression Scale (EDS). Logistic regression models were used to examine the
      association of depressive symptoms with baseline socio-demographic
      characteristics and psychosocial indicators. RESULTS: The prevalence of antenatal
      depressive symptoms, using a cut-off of EDS score >= 10, was 20.1%. Depressive
      symptoms were reported more by women of lower family income and had self-reported
      history of depression prior to pregnancy, with women in the third trimester
      having higher odds of antenatal depressive symptoms compared to those in the
      second trimester. Pregnancy-related anxiety, higher perceived stress levels, and
      post-traumatic stress disorder symptoms were comorbid with the presence of
      depressive symptoms. CONCLUSION: The findings showed that one in five pregnant
      women in Kuwait experiences antenatal depressive symptoms and that these symptoms
      are comorbid with other mental health problems. Screening for antenatal
      depression and providing support to pregnant women should be considered.

PMID- 30097137
TI  - The sleep and sex survey: Relationships between sexual function and sleep.
AB  - OBJECTIVE: Distress and dysfunction in sleep and sex are both very common, and
      have been found to be separately related to anxiety, depression, and stress. Even
      so, and despite evidence linking obstructive sleep apnea and erectile
      disfunction, the connections between sleep and sex are largely understudied.
      METHOD: A large (N = 703) survey of people in the United States between 18 and 65
      years old was conducted using Mechanical Turk, an on-line crowd-sourcing
      platform. Approximately 30% of participants were Black, Hispanic, Asian, or
      Native American, 8% identified as lesbian, gay or bisexual, and the sampling
      structure ensured an even gender distribution in each of 5 age strata. The
      Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI),
      International Index of Erectile Function (IIEF), and Female Sexual Function Index
      (FSFI) assessed sleep and sexual dysfunction; the Perceived Stress Scale (PSS),
      Patient Health Questionnaire (PHQ-9), and General Anxiety Disorder scale (GAD-7)
      measured stress, depression, and anxiety to measure variance. RESULTS: We found a
      significant connection between insomnia severity and sexual function. The
      relationship remained significant after accounting for the shared variability
      associated with depressive and anxious symptoms, and perceived stress.
      CONCLUSION: Given this relationship, clinicians observing dysfunction in one area
      should routinely assess for dysfunction in the other. Further research will be
      required to determine (a) if treatment of one has an effect on the other, and (b)
      if this connection is related to a common psychopathological factor and/or is a
      conditioned association related to the commonly shared context of bed.

PMID- 30097138
TI  - Mental health is a risk factor for poor outcomes in cardiac patients: Findings
      from the national DenHeart survey.
AB  - OBJECTIVE: To explore (i) the prevalence of cardiac risk factors (obesity,
      smoking, excessive alcohol consumption and medication non-adherence) among
      cardiac patients with depression and anxiety, (ii) associations between
      depression and anxiety scores and cardiac risk factors and (iii) the association
      of depression and anxiety and cardiac risk factors with mortality, and their
      population attributable risk. METHODS: A national cross-sectional study using
      patient-reported outcomes at discharge and national register data. For one year
      (April 15th 2013 to April 15th 2014) all patients discharged or transferred from
      the five Danish Heart Centres were included in the study. A total of 14,239
      patients answered the HADS questionnaire, response rate 51%. RESULTS: Mean age
      was 64.8 years and 69% were male. Patients with depression or anxiety (HADS-D or
      HADS-A score >= 8) had 30% and 45%, respectively, higher odds of being current
      smokers; 19% and 37% higher odds of being obese and 31% and 24% higher odds of
      excessive alcohol consumption. Depressive patients had 34% higher odds of being
      non-adherent to their medication. At one-year follow-up, patients with depression
      (HADS-D score >= 11) had the highest attributable risk associated with mortality
      followed by: smoking, ischemic heart disease, anxiety, diabetes, hypertension
      chronic obstructive pulmonary disease and excessive alcohol consumption.
      CONCLUSION: Depression and anxiety in patients with cardiac disease is associated
      with cardiac risk behaviour such as smoking, obesity, excessive alcohol
      consumption and medication non-adherence. Depression and anxiety have an
      attributable risk associated with mortality that is comparable to other well
      known risk factors such as smoking.

PMID- 30097140
TI  - Longitudinal associations between risk appraisal of base stations for mobile
      phones, radio or television and non-specific symptoms.
AB  - INTRODUCTION: Studies found that higher risk appraisal of radiofrequency
      electromagnetic fields is associated with reporting more non-specific symptoms
      such as headache and back pain. There is limited data available on the
      longitudinal nature of such associations and what aspects of risk appraisal and
      characteristics of subjects are relevant. OBJECTIVE: To examine cross-sectional
      and longitudinal associations between risk appraisal measures and non-specific
      symptoms, and assess the role of subject characteristics (sex, age, education,
      trait negative affect) in a general population cohort. METHODS: This study was
      nested in the Dutch general population AMIGO cohort that was established in
      2011/2012, when participants were 31-65 years old. We studied a sample of
      participants (n = 1720) who filled in two follow-up questionnaires in 2013 and
      2014, including questions about perceived exposure, perceived risk, and health
      concerns as indicators of risk appraisal of base stations, and non-specific
      symptoms. RESULTS: Perceived exposure, perceived risk, and health concerns,
      respectively, were associated with higher symptom scores in cross-sectional and
      longitudinal analyses. Only health concerns (not perceived exposure and perceived
      risk) temporally preceded high symptom scores and vice versa. Female sex, younger
      age, higher education, and higher trait negative affect were associated with
      higher risk appraisal of mobile phone base stations. DISCUSSION: The findings in
      this study strengthen the evidence base for cross-sectional and longitudinal
      associations between higher risk appraisal and non-specific symptoms in the
      general population. However, the directionality of potential causal relations in
      non-sensitive general population samples should be examined further in future
      studies, providing information to the benefit of risk communication strategies.

PMID- 30097139
TI  - Quality of life in patients with nonalcoholic fatty liver disease: A systematic
      review.
AB  - OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent
      medical condition, which may lead to severe complications including cirrhosis and
      hepatocellular carcinoma. Its chronic course and its association with obesity and
      diabetes mellitus augment the long-term impact of NAFLD on patients' health and
      quality of life (QoL) and put great strain on healthcare systems worldwide.
      Research is growingly focusing on NAFLD patients' QoL in an attempt to describe
      the full spectrum of disease burden and tackle its future consequences. Relevant
      studies are characterized by sample heterogeneity and provide conflicting
      findings which should be interpreted with the use of a systematic and integrative
      approach. In this context, our aim was to conduct a systematic literature review
      on the topic of NAFLD patients' QoL. METHODS: We performed a systematic search of
      PubMed, ScienceDirect and GoogleScholar databases according to the guidelines of
      the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA)
      protocol. RESULTS: Our search yielded 14 suitable articles reporting data from
      almost 5000 patients. All authors agree that NAFLD patients' QoL is impaired
      especially in the physical sub-domain. In addition, several demographic, clinical
      and histopathological parameters have emerged as major determinants of patients'
      QoL. However, future studies are needed to further clarify these issues.
      CONCLUSIONS: NAFLD patients report poor physical QoL. QoL impairment is
      associated with a variety of disease-related parameters, mostly the presence of
      fatigue and cirrhosis.

PMID- 30097142
TI  - Daytime sleepiness and its relationships to fatigue and autonomic dysfunction in
      adults with spinal cord injury.
AB  - OBJECTIVE: To determine the extent of daytime sleepiness in adults with spinal
      cord injury (SCI) and investigate the contribution of fatigue and autonomic
      function to sleepiness status. METHODS: Participants included 45 adults with SCI
      attending outpatient services or living in the community and 44 able-bodied
      controls. The Oxford Sleep Resistance Test (OSLER) was used to assess daytime
      sleepiness, while eye blink rate duration (electrooculography) and the Iowa
      Fatigue Scale assessed fatigue. Heart rate variability (HRV) was used to assess
      autonomic function. Survival analysis (Kaplan Meier) was used to estimate the
      rate of loss in participation in the OSLER task, as a measure of daytime
      sleepiness. Repeated measures ANOVA was used to determine HRV differences between
      groups. Regression analysis was used to establish factors that contributed to
      daytime sleepiness. RESULTS: Participants with high lesions ("T3 and above") had
      significantly increased daytime sleepiness. OSLER results revealed only 33% of
      those with high lesions remained awake during the task. Those with high lesions
      also had significantly reduced sympathetic activity while no differences in
      parasympathetic activity were found between groups. Lesion completeness had no
      effect. Standardized variation in heart rate, slow eye blinks, low frequency HRV
      and self-reported fatigue contributed to daytime sleepiness. CONCLUSION:
      Neurological lesions at "T3 or above" have an increased risk of daytime
      sleepiness, impacting on independence in daily functional tasks and work
      performance. Autonomic imbalance alters cardiovascular control, affecting health
      and wellbeing. The interaction of these factors requires further investigation.

PMID- 30097144
TI  - Raphael M. Herr: 2018 EAPM Elsevier Young Investigator Award Recipient.

PMID- 30097141
TI  - Predictors of completion of a psychological-behavioral intervention in acute
      coronary syndrome patients.
AB  - OBJECTIVE: Dropout from health behavior interventions in patients with heart
      disease is a major clinical issue that can impact recovery and prognosis.
      Positive psychology (PP)-based treatments have the potential to promote health
      behaviors, but predictors of PP intervention completion have not been examined in
      persons with heart disease. METHODS: Among 128 patients receiving a phone-based
      PP intervention to promote physical activity among acute coronary syndrome (ACS)
      patients, numerous baseline sociodemographic, medical, and psychological
      variables, along with self-reported pre/post improvements in happiness and
      optimism (on 0-10 Likert scales) associated with an initial PP exercise, were
      examined as potential predictors of intervention completion. Logistic and linear
      regression analyses were used to assess relationships between these predictors
      and (a) intervention completion (at least 4 of 8 sessions completed) and (b)
      number of total sessions completed. RESULTS: No patient characteristic was
      associated with greater likelihood of completing the PP intervention. However,
      immediate pre-post change in optimism following the initial exercise was
      associated with intervention completion (odds ratio = 1.98; 95% confidence
      interval: 1.28-3.05; p = .002; mean post-exercise increase in optimism 0.79 [SD
      1.52] in completers vs. mean optimism decrease of 0.59 [SD 1.42] in non
      completers). CONCLUSIONS: Pre-post change in optimism with a single PP activity
      predicted completion of an 8-week PP-based health behavior intervention in post
      ACS patients. This information could be used clinically by having potential
      enrollees complete a single PP activity to assess intervention fit.

PMID- 30097145
TI  - Editorial on "Contemporary theory of enantioseparations in capillary
      electrophoresis" by Bezhan Chankvetadze.

PMID- 30097143
TI  - Predictors of pain, urinary symptoms and quality of life in patients with chronic
      pelvic pain syndrome (CPPS): A prospective 12-month follow-up study.
AB  - OBJECTIVE: Chronic pelvic pain syndrome (CPPS) can affect both men and women and
      often causes substantial impairment to quality of life. Although cross-sectional
      studies have suggested that psychosocial aspects may constitute important factors
      in the etiology and maintenance of CPPS, longitudinal studies are rare.
      Therefore, the present study examines psychosocial factors as prospective
      predictors of pain intensity, urinary symptoms and impediments to quality of life
      in men and women with CPPS. METHODS: Data were collected from patients during
      visits to a specialized, interdisciplinary outpatient clinic and after 12 months.
      Outcomes included pain intensity, urinary symptoms and impediments to quality of
      life, all of which were measured with the NIH-CPSI. Age, sex, depressive-anxious
      symptomatology (PHQ-ADS), pain catastrophizing (PCS), health anxiety (WI-7) and
      social support (FSozU) were examined as predictors in multivariate linear
      regressions. RESULTS: Data from 109 patients (59.6% female; age M = 49.3, SD =
      16.7) were analyzed. Pain severity (beta = .30, p = .004), age (beta = .22, p =
      .02), urinary symptoms (beta = .24, p = .01) and depressive-anxious
      symptomatology (beta = .29, p = .009) at baseline emerged as predictors of pain
      at follow-up. Urinary symptoms were predicted by urinary symptoms (beta = .53, p
      < .001) and depressive-anxious symptomatology (beta = .25, p = .01) at baseline;
      impediments to quality of life were predicted by depressive-anxious
      symptomatology (beta = .27, p = .01). CONCLUSION: Psychological factors,
      especially depressive-anxious symptomatology, predict CPPS-specific symptom
      severity and impediments to quality of life after 12 months and thus
      substantially contribute to the chronification of CPPS. It is recommended to
      address anxiety and depression in patients with CPPS as early as possible in
      biopsychosocially oriented treatment approaches.

PMID- 30097146
TI  - A new PNPLA6 mutation presenting as Oliver McFarlane syndrome.

PMID- 30097147
TI  - Multimodal imaging findings during severe attacks of familial hemiplegic migraine
      type 2.
AB  - BACKGROUND: Familial hemiplegic migraine (FHM) is a rare monogenic form of
      migraine with aura with three distinct genetic subtypes (FHM1-3). Imaging studies
      during acute FHM attacks are scarce in the literature. This is particularly true
      for the FHM2 subtype. PATIENTS AND METHODS: In this monocentric study, we
      retrospectively evaluated imaging data of four different patients with
      genetically confirmed FHM2. Analysis comprised a total of eight cMRI and two CT
      perfusion studies, which were obtained during a total of six different attacks.
      RESULTS: cMRI investigations at all available time-points were without evidence
      of cytotoxic edema. The most prominent finding (four attacks in three patients)
      was swelling and/or cortical hyperintensity of the affected cerebral hemisphere
      on T2/FLAIR-weighted MRI. Further changes, encountered only in a few patients,
      included increased perfusion of the affected hemisphere (as assessed by perfusion
      CT) as well as dilatation of the middle cerebral artery. CONCLUSION: Our data
      from a sizeable cohort of FHM2 patients highlight that swelling / cortical
      hyperintensity of the clinically affected cerebral hemisphere - which has been
      previously reported mainly in FHM1 - can be observed also in FHM2. Further, they
      suggest that these changes, which tend to be present not in the very beginning,
      but rather later on during attacks, may be a possible correlate of the prolonged
      attack duration in our patients.

PMID- 30097148
TI  - The influence of levodopa, entacapone and homocysteine on prevalence of
      polyneuropathy in patients with Parkinson's disease.

PMID- 30097149
TI  - Peripheral neuropathic pain in idiopathic Parkinson's disease: Prevalence and
      impact on quality of life; a case controlled study.
AB  - BACKGROUND AND PURPOSE: Pain is a frequent and debilitating non-motor symptom of
      Idiopathic Parkinson's Disease (IPD). The present study investigated the
      prevalence of pain and specifically peripheral neuropathic pain (PNP) in IPD, and
      ascertained any impact of PNP on quality of life (QoL). METHODS: Patients with
      IPD and age- and gender-matched controls were screened for overall pain using the
      King's Parkinson's Pain Scale (KPPS). PNP was assessed using the Michigan
      Neuropathy Screening Instrument (MNSI). QoL was assessed using the 36-Item Short
      Form Survey (SF-36). RESULTS: Fifty-one patients and 51 age and gender matched
      controls were recruited. The prevalence of overall pain was similar in the two
      groups (88.2% versus 94.1%, p = 0.487). However, patients with IPD had higher
      KPPS scores in fluctuation-related (4.9 +/- 6.9 vs 1.1 +/- 2.6, p < 0.001),
      nocturnal (6.6 +/- 7.5 vs 1.7 +/- 4.2, p < 0.001) and oro-facial (0.6 +/- 2.0 vs
      0.0 +/- 0.0, p = 0.040) domains compared to controls. Patients with IPD
      experienced more PNP compared to healthy control subjects (35.3% versus 13.7%, p
      = 0.011). After adjusting for age, gender, disease duration and overall KPSS
      score, PNP correlated negatively with physical functioning score (beta -0.290, p
      = 0.036), emotional role limitations score (beta -0.319, p = 0.032) and general
      health perception score (beta -0.342, p = 0.014) domains of SF-36. CONCLUSION:
      Peripheral neuropathic pain is prevalent in IPD and has a significant impact on
      QoL. The presence of burning pain is suggestive of small fibre neuropathy, but
      this symptom is not featured in KPSS and, therefore, a revision of the KPSS
      should be considered.

PMID- 30097150
TI  - Levodopa-responsive truncal tremor in a patient with spinocerebellar ataxia type
      3.

PMID- 30097151
TI  - Crossed aphasia in nonfluent variant of primary progressive aphasia carrying a
      GRN mutation.

PMID- 30097152
TI  - Superficial siderosis associated with duplicated dura mater detected by CISS
      reverse MRI.
AB  - Superficial siderosis (SS) of the central nervous system is a rare disease caused
      by chronic or repeated hemorrhages in the subarachnoid space. Closure of dural
      defects is an effective therapy for SS. Conventional magnetic resonance imaging
      (MRI), however, cannot sufficiently detect dural tears. To better detect these
      defects, we analyzed the clinical data of consecutive patients admitted to our
      department with SS and performed constructive interference in steady-state (CISS)
      reverse MRI of the brain and spinal cord. CISS reverse method emphasizes the
      contrast between the dura and cerebrospinal fluid, enabling detection of dural
      defects better than usual T2-weighted MRI. CISS reverse MRI detected fluid-filled
      collections in five of the seven SS patients we studied. These images showed that
      the fluid-filled collections were packed within duplicated dura mater. In three
      of the five, dural defects were confirmed intraoperatively. We postulate that
      fluid-filled collections are actually derived from dissection of the dura mater.
      In accordance with the Monro-Kellie hypothesis, we propose that CSF transferal
      into the fluid-filled collections via dural defects induces an increase in blood
      volume and promotes the exudation of blood from engorged vessels. In patients
      with SS, it is very important to repair dural defects to prevent further
      associated neurological impairment. CISS reverse MRI is useful for detecting such
      dural defects.

PMID- 30097153
TI  - Rapid-onset dystonia-parkinsonism preceded by a single episode of subacute
      persisting hemiparesis: Expanding the ATP1A3-related disorders phenotype.

PMID- 30097154
TI  - In-hospital delays to stroke thrombolysis: Out of hours versus regular hours and
      reduction in treatment times through the creation of a 24/7 mobile thrombolysis
      team.
AB  - BACKGROUND: The main aim of this study was to evaluate the impact of the
      implementation of a mobile thrombolysis team (MTT) on time to thrombolysis
      treatment depending on patient admission time: regular hours (RH) or out of hours
      (OH). METHODS: 504 consecutive patients treated with IV tPA or with combined IV
      tPA and mechanical thrombectomy for acute ischemic stroke were retrospectively
      included between 1st January 2013 and 31st December 2017. Three sub-periods were
      identified: 2013-2014, 2015-2016, and 2017 during which patients were treated
      with the usual care (UC), by the MTT or with UC according to their time of
      admission, or by the MTT, in the three time periods respectively. We compared in
      hospital delays according to patient admission time. RESULTS: In 2013-2014, 133
      patients were included. Both median door-to-needle (DTN) and imaging to needle
      (ITN) times were shorter for patients admitted during RH than OH, respectively 75
      min versus 85 min and 52 min versus 57 min (P < 0.05), and the proportion of
      patients with DTN <= 60 min was 23% versus 9% (P < 0.05), respectively. In 2015
      2016, 223 patients were included. DTN and ITN times were shorter for patients
      admitted during RH and treated by the MTT than during OH with UC, respectively 54
      min versus 78 min and 24 min versus 47 min (P < 0.001), and the proportion of
      patients with DTN <= 60 min was 64% versus 21% (P < 0.001), respectively. In
      2017, there was no difference concerning in-hospital delays regardless of patient
      admission time (P > 0.05). DISCUSSION: DTN time was significantly longer for
      patients admitted OH. We suggest that the implementation of an around-the-clock
      MTT would allow a reduction of in-hospital delays and similar times to
      thrombolysis treatment regardless of admission time.

PMID- 30097156
TI  - Effects of cerebellar magnetic stimulation on chronic post-lateral medullary
      infarction dizziness: A proof-of-principle cohort study.
AB  - BACKGROUND AND PURPOSE: Lateral medullary infarction (LMI) sometimes causes long
      lasting dizziness. Although the precise mechanism of chronic post-LMI dizziness
      is unknown, a cerebellar control disorder of the vestibulo-ocular reflex (VOR)
      has been reported in such patients. We conducted a proof-of-principle cohort
      study to assess the potential efficacy of cerebellar repetitive transcranial
      magnetic stimulation (rTMS) as treatment for chronic post-LMI dizziness. METHODS:
      We first applied cerebellar rTMS in healthy volunteers (n = 11) and showed that
      cerebellar intermittent theta burst stimulation (iTBS) affected
      vestibulocerebellar neural activity. Then, between September and December 2015,
      we enrolled six patients (aged>=20 years) with chronic post-LMI dizziness
      (duration>=6 months), applied cerebellar rTMS (iTBS for 5 days), and followed
      these patients up for up to 25 months for clinical symptoms (Dizziness Handicap
      Inventory [DHI]), signs (nystagmus), and VOR gain. RESULTS: Four of the six
      patients completed the study without complications. After rTMS, DHI scores were
      reduced (mean pre-rTMS DHI score minus post-rTMS DHI score was 13.0 [P = 0.036])
      with disappearance of the ipsilesional nystagmus characteristic of the post-LMI
      dizziness. Reduction in the absolute VOR gain (mean pre- rTMS gain minus post
      rTMS gain in the ipsilesional direction was 0.135 [P = 0.036] and that in the
      contralesional direction was 0.137 [P = 0.031]) were also associated with reduced
      DHI scores. Relative cerebellar blood flow to the brainstem was increased in four
      of five patients. The effects of cerebellar rTMS did not always persist, and
      three of four patients elected to undergo more than one rTMS series. The repeat
      cerebellar rTMS treatments had same beneficial effects. CONCLUSION: Our study
      showed, for the first time, the potential efficacy of cerebellar rTMS for
      treatment of chronic post-LMI dizziness. The short duration of the cerebellar
      rTMS effects can be compensated for by repeating the rTMS treatment every few
      months. Further large-scale randomized studies are warranted to confirm our
      findings.

PMID- 30097155
TI  - Leucine-rich alpha-2 glycoprotein in the cerebrospinal fluid is a potential
      inflammatory biomarker for meningitis.
AB  - BACKGROUND: Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for
      inflammatory diseases. We evaluated the levels of LRG, interleukin (IL)-6, and
      tumor necrosis factor (TNF)-alpha in the cerebrospinal fluid (CSF) of children
      with meningitis. METHODS: CSF samples from 10 patients with bacterial meningitis
      (BM) and 10 with aseptic meningitis (AM) were evaluated. Samples from 10 patients
      with febrile status (FS) were used as controls. LRG levels were measured using a
      two-site enzyme immunoassay. IL-6 and TNF-alpha levels were measured using a
      multiplex bead-based assay. CSF examination of patients with BM at the
      convalescent stage was also conducted. RESULTS: LRG and TNF-alpha levels in
      patients with BM, and IL-6 levels in patients with BM and AM showed significant
      increase compared with those in FS. Patients with BM at the convalescent stage
      showed significantly diminished LRG and IL-6 levels. LRG and IL-6 levels in CSF
      were indicated to be effective predictors for BM (LRG, AUC = 0.91; IL-6, AUC =
      0.85). Only LRG levels showed a significant difference between patients with BM
      and AM (AUC = 0.78, P = 0.034). CONCLUSIONS: LRG level could be a sensitive
      inflammatory biomarker for inflammatory diseases of the central nervous system,
      comparable with IL-6 level.

PMID- 30097157
TI  - Cholinergic and purinergic systems: A key to multiple sclerosis?
AB  - Multiple sclerosis (MS) commonly affects young adults and leads to a decreased
      quality of life due to different signs and symptoms that induce physical,
      cognitive, social, and psychological challenges. This disease, an autoimmune
      neurological disorder, is characterized by chronic inflammatory demyelination and
      axonal degeneration of the central nervous system (CNS). To date, its etiology is
      unknown. A large number of physiological functions are regulated by the
      cholinergic system because the acetylcholine (ACh) is released from cholinergic
      neurons and acts on other neurons, most of them not cholinergic in the brain, as
      well as in various nonneuronal cells, such as those of the immune system and
      blood; thus, it is considered an important modulatory pathway of both the central
      and peripheral nervous systems. Furthermore, the purinergic system has a
      significant role in neurotransmission as well as immune and inflammatory
      responses. Accumulating evidence has suggested the presence of a strong
      association between these systems and MS. Therefore, this review aims to present
      and discuss the main mechanisms that potentially explain the influence of the
      cholinergic and purinergic systems in multiple sclerosis. These mechanisms are
      discussed in light of available scientific evidence in humans and animal
      experimental models of MS. We hope that this review provides a better
      understanding of this subject, helping to guide future research and potential
      novel therapeutic strategies for patients with MS.

PMID- 30097158
TI  - Oral health promotion using leaflets or e-learning seem to improve oral health
      knowledge and habits and plaque and gingival index scores.

PMID- 30097160
TI  - There seem to be no important differences between the 1-year outcomes of
      mandibular overdentures supported by 2 implants placed in the canine region and
      in the premolar region when the canine region is not an option.

PMID- 30097159
TI  - Oral hygiene instruction does not seem to have a distinct effect in patients with
      chronic periodontitis and high caries experience.

PMID- 30097161
TI  - A high proportion of children undergoing dental treatment under general
      anesthesia experience postoperative dental pain.

PMID- 30097162
TI  - Characterisation of laryngo-pharyngeal reflux disease in old and ageing patients.
AB  - OBJECTIVES: To characterize laryngo-pharyngeal reflux (LPR) in patients over 60
      years of age. METHODS: Retrospective review of patients over 60 years of age with
      symptoms suspicious of LPR, seen from 2005 to 2014 at an ENT Department of an
      academic hospital. Eighty-five consecutive patients (54 females, 31 males) who
      had completed a dual-sensor 24-hour pH-metry were included (considered "gold
      standard" in LPR diagnosis). Body mass index, and reflux information and
      interventions were revised. pH-metries were evaluated according to DeMeester &
      Johnson's criteria. Symptoms were assessed according to the Reflux Symptom Index
      (RSI) and classified as abnormal if score was >=13. A naso-fibro-laryngoscopy
      enabled findings to be documented according to the Reflux Finding Score (RFS),
      and they were classified as abnormal if the score was >=7. RESULTS: The patients'
      mean age was 67 years. A positive pH-metry was present in 70 patients (82.5%).
      Fifty patients (59%) had abnormal body mass index, and almost 90% of them had an
      abnormal pH-metry. Mean RSI score was 9.8, with abnormal results in 24 patients
      (28%). Only 20 patients (23%) with abnormal RSI had a positive pH-metry.
      Posterior commissure hypertrophy was the most common finding (90% of patients).
      Mean RFS score was 9.07, with abnormal results in 69 patients (81%). Sixty-one
      patients (70%) with abnormal RFS had a positive pH-metry. Only 18 patients (20%)
      had coincidental abnormal pH-metry, RSI, and RFS. CONCLUSIONS: In ageing
      patients, abnormal body mass index is strongly associated with abnormal pH-metry.
      RSI is a weak indicator of LPR, whereas RFS has a moderate value.

PMID- 30097163
TI  - Validation of the measures of cepstral peak prominence as a measure of dysphonia
      severity in Spanish-speaking subjects.
AB  - INTRODUCTION AND OBJECTIVES: Perceptual rating of overall voice quality and other
      more specific perceptual dimensions is difficult, as such judgments depend on the
      listener's subjectivity. Thus, finding objective, valid, and accessible clinical
      measures to include in comprehensive voice evaluation protocols is a priority.
      The purposes of this study were to 1) determine the diagnostic accuracy of a
      single acoustic measure, smoothed cepstral peak prominence (CPPS), to predict
      voice disorder status from sustained vowels and connected speech samples using
      the software Praat; 2) to determine the relationship between measures of CPPS and
      perceptual ratings of vocal quality; and 3) describe the normative values of
      CPPS. METHOD: Measures of CPPS were obtained from connected speech and sustained
      vowel recordings of 72 Spanish-speaking subjects with voice disorders and 52
      nondysphonic Spanish-speaking subjects with no vocal disorders using freely
      downloadable Praat software. IBM SPSS Statistics software version 23 was used to
      complete the statistical analyses. RESULTS: results revealed a 70% sensitivity
      rate, a specificity rate of 85%. Estimated severity for sustained vowels and
      connected speech were strongly correlated and significantly associated with
      listener ratings of dysphonia severity. CONCLUSIONS: A single acoustic measure of
      CPPS was highly predictive of voice disorder status using Praat software.
      Clinicians may consider using CPPS to complement clinical voice evaluation and
      screening protocols.

PMID- 30097164
TI  - A comparison of the effects of selective and non-selective mineralocorticoid
      antagonism on glucose homeostasis of heart failure patients with glucose
      intolerance or type II diabetes: A randomized controlled double-blind trial.
AB  - Mineralocorticoid receptor antagonists (MRAs) decrease morbidity and mortality in
      patients with heart failure (HF). However, spironolactone, a non-selective MRA,
      has been shown to exert a harmful effect on glucose homeostasis. The objective of
      this multicenter, randomized, controlled, double-blind trial was to compare the
      effects of spironolactone to those of the selective MRA eplerenone on glucose
      homeostasis among 62 HF patients with glucose intolerance or type II diabetes.
      Trial registration number:NCT01586442.

PMID- 30097165
TI  - Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival.
AB  - Corneal transplantation is the most prevalent form of tissue transplantation. The
      success of corneal transplantation mainly relies on the integrity of corneal
      endothelial cells (CEnCs), which maintain graft transparency. CEnC density
      decreases significantly after corneal transplantation even in the absence of
      graft rejection. To date, different strategies have been used to enhance CEnC
      survival. The neuropeptide vasoactive intestinal peptide (VIP) improves CEnC
      integrity during donor cornea tissue storage and protects CEnCs against oxidative
      stress-induced apoptosis. However, little is known about the effect of exogenous
      administration of VIP on corneal transplant outcomes. We found that VIP
      significantly accelerates endothelial wound closure and suppresses interferon
      gamma- and tumor necrosis factor-alpha-induced CEnC apoptosis in vitro in a dose
      dependent manner. In addition, we found that intracameral administration of VIP
      to mice undergoing syngeneic corneal transplantation with endothelial injury
      increases CEnC density and decreases graft opacity scores. Finally, using a mouse
      model of allogeneic corneal transplantation, we found for the first time that
      treatment with VIP significantly suppresses posttransplantation CEnC loss and
      improves corneal allograft survival.

PMID- 30097167
TI  - Editorial: 2016 Annual Meeting of the Pavlovian Society.

PMID- 30097166
TI  - Risk factors for 30-day readmission after adrenalectomy.
AB  - BACKGROUND: Readmissions represent a substantial burden to the health care
      system. Risk factors for 30-day readmission after adrenalectomy were examined.
      METHODS: Patients who underwent adrenalectomy were selected from the American
      College of Surgeons National Surgical Quality Improvement Program database from
      2011 to 2015. RESULTS: Among 4,221 patients who underwent adrenalectomy, 216
      (5.1%) were readmitted. On multivariate analysis, pre-operative predictive
      factors associated with readmission were American Society of Anesthesiologists
      classification (odds ratio [OR] 1.4, confidence interval [CI] 1.1-1.8),
      disseminated cancer (OR 1.6, CI 1.1-2.5), and adrenal injury (OR 10.9, CI 1.8
      68.9). Elective procedures had fewer readmissions (OR 0.50, CI 0.33-0.76). and
      procedures with greater relative value units had greater readmission rates (OR
      1.01, CI 1.004-1.02). An open adrenalectomy (21% of patients) had a higher rate
      of readmission than a laparoscopic approach (8.0% vs 4.3%, OR 1.5, CI 1.1-2.0).
      Postoperative risk factors affecting readmission included reoperations (OR 3.2,
      CI 1.3-8.0), wound complications (OR 6.6, CI 3.8-11.7), systemic infection (OR
      6.5, CI 3.9-10.7), renal complications (OR 7.1, CI 2.6-19.2), venous thrombotic
      events (OR 11.3, CI 5.6-22.6), and discharge to home (OR 0.40, CI 0.22-0.73).
      CONCLUSION: Encouraging the appropriate use of laparoscopic adrenalectomy,
      preventing venous thrombotic events and surgical infections, and improving early
      post-operative follow-up in high-risk patients may decrease readmissions.

PMID- 30097168
TI  - Systematic review of in-vivo neuro magnetic resonance spectroscopy for the
      assessment of posttraumatic stress disorder.
AB  - Posttraumatic stress disorder (PTSD) is a trauma and stressor-related disorder
      that results in complex somatic, cognitive, affective and behavioural effects,
      after exposure to traumatic event(s). Conventional imaging (T1 and T2 weighted
      magnetic resonance imaging) has little to offer in the way of diagnosis of mental
      health conditions such as PTSD and there is currently no objective diagnostic
      test available. Magnetic resonance spectroscopy (MRS) allows for non-invasive
      measurement of metabolites and neurochemicals in the brain using a conventional
      MRI scanner and offers the potential to predict, diagnose and monitor PTSD. This
      systematic review summarises the results of 24 MRS studies, performed between
      1998 and 2017, to measure neurochemical differences, occurring as a consequence
      of PTSD. The most consistent finding in subjects with PTSD is lower N
      acetylaspartate levels in the hippocampus and anterior cingulate cortex, with and
      without atrophic change. More recent studies, using more advanced techniques and
      modern hardware, have shown evidence of glutamatergic dysfunction and differences
      in gamma-aminobutyric acid levels in the brain of patients with PTSD. Conflicting
      results have been reported in choline-containing metabolites and there is
      emerging evidence of glutathione being affected. Myo-inositol and creatine are
      unchanged in the majority of studies.

PMID- 30097169
TI  - Changes in Left Atrial Function After Transcutaneous Mitral Valve Repair.
AB  - Left atrial (LA) reverse remodeling occurs after transcatheter mitral valve
      repair, but additional data are needed about changes in LA function. Changes in
      LA stiffness in patients undergoing MitraClip implantation were evaluated.
      Baseline, procedural, and 30-day follow-up clinical and imaging data of patients
      undergoing MitraClip were reviewed. LA operating chamber stiffness was calculated
      as the ratio of systolic change in LA pressure to LA systolic strain and to
      stroke volume. Matched preprocedure and postprocedure LA strain analyses were
      performed in 35 patients, 21 with primary and 14 with functional mitral
      regurgitation (MR). Procedural success occurred in 34 of 35 cases with
      significant improvement of all invasive hemodynamic parameters. LA operating
      chamber stiffness decreased significantly in the overall population (p <0.001).
      At follow-up, sustained improvement in MR severity occurred, together with left
      ventricular (LV) and LA reverse remodeling. After MitraClip deployment, LA
      operating chamber stiffness showed a significant correlation with follow-up
      pulmonary artery systolic pressure, LV end systolic volume, and LV EF,
      irrespective of MR etiology (p <0.05). A significant inverse correlation was seen
      between change in LA operating chamber stiffness and improvement in 6-min walking
      distance. In conclusion, LA operating chamber stiffness decreases after MitraClip
      deployment, irrespective of MR etiology. It is related to pulmonary artery
      systolic pressure and functional status.

PMID- 30097170
TI  - Correlation of mutation status and morphological changes in essential
      thrombocythaemia and myelofibrosis.

PMID- 30097171
TI  - Comparison of cranial fluctuating asymmetry between normal and pathological
      specimens from a modern Thai skeletal group.
AB  - The purpose of this study was to compare fluctuating asymmetry (FA) levels across
      cranial modules of normal and pathological cranial specimens. It was examined
      whether pathological specimens have significantly higher FA scores than normal
      specimens in cranial regions affected by a developmental disorder. For this
      study, a modern Thai skeletal sample from Chulalongkorn University was analyzed.
      Ninety-two cranial landmarks were digitized on 66 adult and eight sub-adult
      normal specimens and on five pathological specimens including two adults with
      abnormal palates, two sub-adults with craniosynostosis, and one sub-adult with
      natal absence of nasal bones. In sub-adults, FA scores of specimens with
      developmental disorders were significantly higher than normal specimens in the
      entire cranium (p = 0.041) and vault (p = 0.025). However, comparisons excluding
      specimen with coronal craniosynostosis were not statistically significant. In
      adult specimens, comparisons of FA scores in each separate cranial module were
      also not statistically significant. These results suggest that elevated cranial
      FA may not be confined to the specific cranial region with the developmental
      disorder.

PMID- 30097172
TI  - What should we tell our worried patients with insomnia about blood pressure?

PMID- 30097173
TI  - Use of an automaton model to suggest methods for cessation of intractable
      fibrillatory activity.
AB  - BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia, and
      permanent AF is an intractable medical problem. If cessation of permanent AF were
      possible, via extensive substrate ablation or multisite stimulation, it could
      significantly improve the public health. METHOD: A cellular automaton composed of
      576 * 576 computerized grid nodes, described in detail previously, was used to
      test hypotheses concerning the cessation of fibrillatory electrical activity. A
      refractory period gradient across the grid, and addition of randomly located
      nonconducting fibers, were utilized as conditions leading to fibrillatory
      activity. A premature S1-S2 stimulus was applied to one grid corner, resulting in
      unidirectional conduction block at some locations, followed by rotational
      activity and random propagation of activation wavelets throughout the grid, none
      of which terminated spontaneously. Simulated ablation lesions of dimension 20 *
      20 grid nodes, imparted at core locations of rotational activity, and multisite
      electrode stimulation (MES) applied at nodes where recovery of excitability had
      occurred, were used in attempts to terminate fibrillatory activity. Six
      impositions of random fiber location were utilized in separate trials. RESULTS:
      Simulated ablation lesions eliminated the targeted swirling vortices; however,
      additional vortices then often appeared at other locations. After ablating
      approximately one third of the grid area, localized vortices were eliminated, but
      individual wavelets continued to propagate about longer viable pathways forming
      at ablation lesions. Thus extensive ablation was unsuccessful in terminating
      arrhythmia. However, MES applied uniformly throughout the grid, with a coupling
      interval slightly longer than the maximum refractory period, terminated
      fibrillatory activity in some trials. More efficaciously, application of MES with
      a coupling interval half the maximum refractory period of the grid succeeded in
      capture of activation at all nodes, and when followed by a doubling of the MES
      coupling interval, resulted in cessation of all fibrillatory activity.
      CONCLUSIONS: It is possible to terminate simulated fibrillatory activity in a
      computerized grid that would otherwise be intractable, using multisite
      stimulation with a coupling interval related to the maximum refractory period of
      the substrate. If each MES stimulating electrode could be individually
      controlled, it would be possible to apply a stimulation pattern mimicking the
      normal heart activation sequence.

PMID- 30097174
TI  - Comment on: "Ultrasonic propagation: A technique to reveal field induced
      structures in magnetic nanofluids" [Ultrasonics 60 (2015) 126-132].
AB  - I have shown that authors (Prakash et al., 2015) to obtained unreasonably good
      agreement between the calculated by using wrong theory and the wrong experimental
      data.

PMID- 30097176
TI  - Expression and modulation of S100A4 protein by human mast cells.
AB  - S100A4 protein is expressed in fibroblasts during tissue remodelling and in
      cancer stem cells and it induces the metastatic spread of tumor cells. In mast
      cells (MCs) S100A4 have been found in some pathological conditions, but its
      function in normal MCs remains to be described. The purpose of this study was to
      characterize the cellular localization of the S100A4 protein in MCs of human
      tissues with inflammatory or tumor disorders and, to determine the consequence of
      reducing its expression in MC response. We found that tissue resident MCs stained
      positive to S100A4. Both human HMC-1 cell line and resting CD34+-derived MCs
      expressed S100A4, whose levels were differentially modulated upon MC activation.
      Downregulation of the S100A4 protein resulted in MC growth inhibition, enhanced
      apoptosis and deregulation of MMP-1 and MMP-10 production. Our results suggest
      that S100A4 is also playing a role in the MC life cycle and functions.

PMID- 30097175
TI  - Allosteric KRas4B Can Modulate SOS1 Fast and Slow Ras Activation Cycles.
AB  - Membrane-anchored Ras family proteins are activated by guanine nucleotide
      exchange factors such as SOS1. The CDC25 domain of SOS1 catalyzes GDP-to-GTP
      exchange, thereby activating Ras. Here, we aim to decipher the activation
      mechanism of KRas4B, a significantly mutated oncogene. We perform large-scale
      molecular dynamics simulations on 12 SOS1 systems, scrutinizing each step in two
      possible KRas4B activation cycles, fast and slow. To activate KRas4B at the CDC25
      catalytic site, the allosteric site in the Ras exchanger motif (REM) domain of
      SOS1 needs to recruit a (nucleotide-bound) KRas4B molecule. Our simulations
      indicate that KRas4B-GTP interacts with the REM allosteric site more strongly
      than with the CDC25 catalytic site, consistent with its allosteric role in the
      GDP-to-GTP exchange. In the fast cycle, the allosteric KRas4B-GTP induces
      conformational change at the catalytic site. The conformational change
      facilitates loading KRas4B-GDP at the catalytic site and opening the KRas4B
      nucleotide-binding site for GDP release and GTP binding. GTP binding reduces the
      affinity of KRas4B-GTP to the CDC25 catalytic site, resulting in its release. By
      contrast, in the slow cycle, KRas4B-GDP binds at the allosteric REM site. The
      limited, altered conformational change that it induces prevents the exact
      alignments of switch I and II of KRas4B. The increasing binding strength at both
      binding sites due to interactions of regions other than switch I and II retards
      GDP release from the catalytic KRas4B, thus KRas4B activation. The accelerated
      activation cycle supports a positive feedback loop with allosteric signals
      communicating between the two Ras molecules and is the predominant, native
      function of SOS. SOS1 activation details may help drug discovery to inhibit Ras
      activation.

PMID- 30097177
TI  - Lactobacillus rhamnosus GG induced protective effect on allergic airway
      inflammation is associated with gut microbiota.
AB  - Great interest has been taken in the use of beneficial bacteria for allergic
      diseases recently, but the underlying mechanisms through which probiotics induces
      immune regulation or immune tolerance are poorly understood. We aimed to explore
      whether Lactobacillus rhamnosus GG (LGG)-induced beneficial effect relates to the
      change of microbiota. LGG was administered orally to mouse model of ovalbumin
      (OVA)-induced allergic airway inflammation. Our findings manifested that LGG
      treatment contributes to protect against OVA-induced allergic airway inflammation
      by expanding mesenteric CD103+DCs and accumulating mucosal Tregs. Moreover,
      protective effect induced by LGG is associated with gut microbiota instead of
      lung flora. Collectively, our findings indicate that LGG induced protective
      effect is associated with gut microbiota and provide a new evidence of probiotic
      application in the allergic airway inflammation.

PMID- 30097178
TI  - [Herpes zoster ophthalmicus in an immunosuppressed patient].

PMID- 30097179
TI  - Study on PID tuning strategy based on dynamic stiffness for radial active
      magnetic bearing.
AB  - The development of industry technology requires magnetic bearings to work in high
      speed conditions. However, the current stiffness and displacement stiffness of
      the magnetic bearing will decrease significantly due to the consequent eddy
      current effect, and that decrease will make the system unstable and even result
      in the rotor drop and instrument damage. Therefore, the traditional Proportional
      Integral-Derivative (PID) method based on constant stiffness is not adaptable for
      high speed conditions. This paper proposes a PID parameters tuning strategy based
      on dynamic stiffness for the radial active magnetic bearing (RAMB). The dynamic
      stiffness model under eddy current effect is established by analyzing the
      equivalent magnetic circuit model in which parameters are frequency-dependent.
      The PID parameters tuning method for RAMB control system including dynamic
      stiffness model is put forward according to the characteristic equation and Routh
      Hurwitz criterion. Different PID parameters are set in simulations and several
      corresponding experiments are conducted. Satisfactory control effects consistent
      with the theoretical analysis are obtained and thus the proposed PID tuning
      strategy is verified to be good. Simulations and experiments in this paper
      provide theoretical guidance for the design of controller parameters and have
      research significance for structural optimization of RAMB.

PMID- 30097180
TI  - Sliding mode approach for formation control of multi-agent systems with unknown
      nonlinear interactions.
AB  - This paper proposes nonlinear control approaches to solve a leader-follower
      formation of multi-agent system with unknown nonlinear interactions. Two
      distributed sliding mode control approaches are suggested here to track a leader
      in a desired formation with compensating unknown nonlinear terms. The nonlinear
      interaction terms can appear in multi-agent systems due to physical connections
      or cooperation between agents. Also the uncertainty in coefficient of control
      input is considered. Super twist algorithm is suggested for investigating this
      problem. Some Lyapunov functions are modified and employed to prove maintaining
      the formation of group, using the proposed sliding mode controllers. A simulation
      result for slung load transporting with quad-rotors is presented to demonstrate
      the capability of the proposed approaches.

PMID- 30097181
TI  - Adaptive sensor fault-tolerant control for a class of multi-input multi-output
      nonlinear systems: Adaptive first-order filter-based dynamic surface control
      approach.
AB  - This paper is concerned with the adaptive fault-tolerant control (FTC) problem
      for a class of multivariable nonlinear systems with external disturbances,
      modeling errors and time-varying sensor faults. The bias, drift, loss of accuracy
      and loss of effectiveness faults can be effectively accommodated by this scheme.
      The dynamic surface control (DSC) technique and adaptive first-order filters are
      brought together to design an adaptive FTC scheme which can reduce significantly
      the computational burden and improve further the control performance. The
      adaptation laws are constructed using novel low-pass filter based modification
      terms which enable under high learning or modification gains to achieve robust,
      fast and high-accuracy estimation without incurring undesired high-frequency
      oscillations. It is proved that all signals in the closed-loop system are
      uniformly ultimately bounded and the tracking-errors can be made arbitrary close
      to zero. Simulation results are provided to verify the effectiveness and
      superiority of the proposed FTC method.

PMID- 30097182
TI  - Identification of risk factors for postoperative recurrent Hirschsprung
      associated enterocolitis.
AB  - This article has been withdrawn at the request of the author(s) and/or editor.
      The Publisher apologizes for any inconvenience this may cause. The full Elsevier
      Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our
      business/policies/article-withdrawal.

PMID- 30097183
TI  - Locomotion, postures, substrate use, and foot grasping in the marsupial
      feathertail glider Acrobates pygmaeus (Diprotodontia: Acrobatidae): Insights into
      early euprimate evolution.
AB  - Debates on early euprimate evolution are related to the understanding of the
      ecological context that promoted their unique adaptations. Currently, these
      discussions mainly revolve around the habitual use of the small-branch niche or
      the frequent utilization of wider, and probably, strongly inclined substrates by
      euprimate ancestors. The current fossil evidence implies a diversity of arboreal
      quadrupedal behaviors for these early euprimates, associated with the use of
      various types of substrates. However, inferring the positional behavior of early
      euprimates based exclusively on fossils fails to unravel the positional
      flexibility in terms of modes and substrate use, which is important for
      understanding key adaptations related to limb postures. Following previous
      research, we studied the positional behavior, substrate use and pedal grasping
      modes of the marsupial feathertail gliders to investigate patterns of arboreal
      behavior that may be analogous to those exhibited by early euprimate ancestors.
      For the purposes of the current study, we observed and filmed 15 male and 20
      female captive adult feathertail gliders Acrobates pygmaeus (Marsupialia:
      Diprotodontia: Acrobatidae) in a large enclosure in the Nocturnal Pavilion of
      Nowe Zoo, Poznan, Poland. Our observations demonstrated a strong preference for
      small and for horizontal substrates, avoidance of large and of vertical ones, a
      diverse positional repertoire mainly composed of quadrupedalism, clambering,
      climbing and gliding, the last occurring from small and oblique and vertical
      substrates, and the dominant use of hallucal grasping, especially on small,
      horizontal and oblique substrates. We thus consider that the generalized profile
      of A. pygmaeus could fit in a stage where the euarchontan heritage of vertical
      clawed activities on large substrates has decreased in favor of the use of small
      moderately inclined substrates efficiently negotiated by diagonal sequence
      quadrupedalism and handled via an apparently powerful hallucal grasp. Competent
      use of small substrates could have further expanded into small vertical
      substrates, which would progressively serve as new climbing platforms and takeoff
      perches for unspecialized leaping. We feel that this stage may have occurred
      early in euprimate evolution, as small body size likely provided the necessary
      behavioral flexibility to exploit various niches. Depending on alternative
      scenarios, it could represent that of the common ancestor of euprimates or be
      rooted at the base of strepsirrhine evolution. This study underscores the
      important of analyzing the behavior of extant models to infer the locomotor
      evolution of euarchontans, primates or euprimates.

PMID- 30097184
TI  - The Oldowan industry from Swartkrans cave, South Africa, and its relevance for
      the African Oldowan.
AB  - The oldest recognized artifacts at the Swartkrans cave hominid-bearing site in
      South Africa have long been known to occur in the Lower Bank of Member 1, now
      dated with the cosmogenic nuclide burial method to ca. 1.8-2.19 Ma. However, the
      affinities of this industry have been debated due to small sample size. In this
      paper we present newly excavated material from the Lower Bank retrieved since
      2005 in the Swartkrans Paleoanthropological Research Project. The sample is now
      large enough to confirm its affinity with the Oldowan industrial complex. The
      assemblage is highly expedient and core reduction strategies are largely casual.
      Although freehand flaking is present, the bipolar technique is most significant,
      even in non-quartz raw materials. The Swartkrans assemblage shows some
      significant contrasts with the Sterkfontein Oldowan, ca. 2.18 Ma, which can be
      explained by its closer proximity to raw material sources, its somewhat different
      geographic context, and its more expedient nature. The Swartkrans Oldowan now
      provides us with the first good indication of Oldowan variability in southern
      Africa, where only two sizeable assemblages have thus far been discovered.
      Comparisons are made with other sites across Africa that help to place this
      variability within our overall understanding of the Oldowan industrial complex.

PMID- 30097185
TI  - [Anesthesia and perioperative challenges for surgical separation of thoraco
      omphalopagus twins: case report].
AB  - BACKGROUND AND OBJECTIVES: Conjoined twins are monozygotic twins physically
      joined at some part of the body. This is a rare phenomenon, estimated between
      1:50,000 to 1:200,000 births. The objective of this report is to present the
      anesthetic management and the perioperative challenges for a separation surgery.
      CASE REPORT: Thoraco-omphalopagus twins were diagnosed by ultrasound and were
      followed by the fetal medicine team of the service. After 11hours of cesarean
      surgery, the pediatric surgical team chose to separate the twins. They were
      monitored with cardioscopy, oximetry, capnography, nasopharyngeal thermometer,
      urinary output, and noninvasive blood pressure. We chose inhaled induction with
      oxygen and 4% Sevoflurane. T1 patient was intubated with a 3.5 uncuffed
      endotracheal tube, and, after three unsuccessful intubation attempts of patient
      T2, a number 1 laryngeal mask was used. After securing the twins' airway, the
      induction was supplemented with fentanyl, propofol, and rocuronium. Mechanical
      ventilation in controlled pressure mode (6mL.kg-1) and lumbar epidural (L1-L2)
      with 0.2% ropivacaine (2.5mg.kg-1) were used. The pediatric surgical team
      initiated the separation of the twins via sternotomy, ligation of hepatic
      vessels. After 2hours of procedure, the separation was completed, continuing the
      surgical treatment of T1 and the support of T2 until his death. CONCLUSIONS:
      Conjoined twin separation surgery is a challenge, which requires planning and
      coordination of a multidisciplinary team during all stages.

PMID- 30097186
TI  - The involvement of NR4A1 and NR4A2 in the regulation of the luteal function in
      rats.
AB  - The nuclear receptor 4A (NR4A) members play important roles in cellular
      proliferation, differentiation and apoptosis. The current study first evaluate
      the expression of ovarian NR4A1 during different luteal stages in rats. Immature
      rats aged 28 days were treated with sequential Pregnant mare serum gonadotropin
      (PMSG) (D -2) / human chorionic gonadotropin (hCG) (D 0) to induce
      pseudopregnancy. Serum progesterone (P4) and ovarian expression of NR4A1 were
      detected by RIA and WB, respectively, at follicle stage (D 0), early (D 2),
      middle (D 7) and late (D 14 and D 20) luteal stages. To confirm the role of NR4A1
      during the luteal regression, rats were treated with prostaglandin F2alpha analog
      (PGF) for 0-8 h on D 7 to detect the expressions of NR4A1 and NR4A2. RIA result
      showed that serum P4 reached highest level on D 7 and then declined. WB results
      showed that there were two types of NR4A1 (NR4A1-L and NR4A1-S) expressed in the
      ovary. The ovarian NR4A1-L decreased at the late luteal stage (D 20). However,
      the NR4A1-S increased at the late luteal stage (D 14). After PGF treatment on D
      7, the expression of NR4A1-S increased which peaked at 0.5-1 h and then declined;
      while NR4A1-L expression did not change within 8 h. Real-time PCR results showed
      that the ovarian NR4A1 mRNA increased within 0.5 h, maintained high at 1 h and
      then declined. The NR4A2 mRNA expression exhibited a similar pattern to that of
      NR4A1 mRNA, though its abundance was not as high as NR4A1. IHC results revealed
      that NR4A1-L was expressed mainly in the cytoplasm of luteal steroidogenic cells,
      faintly expressed in the follicle theca cells, oocytes and the pericytes; while
      NR4A2 was primarily localized in the cytoplasm of luteal steroidogenic cells. In
      conclusion, all these results demonstrate that NR4A2 as well as NR4A1 might be
      involved in the luteal development and luteolysis in rats.

PMID- 30097187
TI  - Soil exposure modifies the gut microbiota and supports immune tolerance in a
      mouse model.
AB  - BACKGROUND: Sufficient exposure to natural environments, in particular soil and
      its microbes, has been suggested to be protective against allergies. OBJECTIVE:
      We aim at gaining more direct evidence of the environment-microbiota-health axis
      by studying the colonization of gut microbiota in mice after exposure to soil and
      by examining immune status in both a steady-state situation and during allergic
      inflammation. METHODS: The gastrointestinal microbiota of mice housed on clean
      bedding or in contact with soil was analyzed by using 16S rRNA gene sequencing,
      and the data were combined with immune parameters measured in the gut mucosa,
      lung tissue, and serum samples. RESULTS: We observed marked differences in the
      small intestinal and fecal microbiota composition between mice housed on clean
      bedding or in contact with soil, with a higher proportion of Bacteroidetes
      relative to Firmicutes in the soil group. The housing environment also influenced
      mouse intestinal gene expression, as shown by upregulated expression of the
      immunoregulatory markers IL-10, forkhead box P3, and cytotoxic T lymphocyte
      associated protein 4 in the soil group. Importantly, using the murine asthma
      model, we found that exposure to soil polarizes the immune system toward TH1 and
      a higher level of anti-inflammatory signaling, alleviating TH2-type allergic
      responses. The inflammatory status of the mice had a marked influence on the
      composition of the gut microbiota, suggesting bidirectional communication along
      the gut-lung axis. CONCLUSION: Our results provide evidence of the role of
      environmentally acquired microbes in alleviating against TH2-driven inflammation,
      which relates to allergic diseases.

PMID- 30097188
TI  - Major coronary evaginations following implantation of bioresorbable vascular
      scaffolds - Clinical and OCT characteristics.
AB  - BACKGROUND: Coronary evaginations can occur after implantation of bioresorbable
      vascular scaffolds (BRS) and may be associated with scaffold thrombosis. Aim of
      this study was to clarify the clinical manifestation, extent and time course of
      coronary artery remodeling in vessel segments that develop angiographically
      detectable evaginations following BRS implantation through optical coherence
      tomography (OCT) analysis. METHODS: In 8 patients, 10 BRS (Absorb, Abbott
      Vascular, Santa Clara, CA, USA) which displayed coronary evaginations in
      clinically driven late invasive coronary angiograms were identified and findings
      were compared to 10 BRS in 8 patients without coronary evaginations. Vessel and
      device geometry was analyzed in serial OCT cross-sections at a spacing of 200
      MUm. Measured BRS dimensions were normalized to the reference vessel size at
      implantation. RESULTS: In OCT, major evaginations on average affected 24 +/- 19%
      of the scaffold length. Scaffolds with major evaginations had a significantly
      larger lumen area than scaffolds without evaginations (mean normalized lumen area
      1.19 +/- 0.58 vs. 0.77 +/- 0.38; p < 0.001), and also displayed a significantly
      larger scaffold area (mean normalized scaffold area: 1.36 +/- 0.6 vs. 1.13 +/-
      0.43; p < 0.001), and scaffold diameter (mean normalized scaffold diameter: 1.17
      +/- 0.33 vs.1.04 +/- 0.19; p < 0.001). Lumen area (r = 0.47; p < 0.001), scaffold
      area (r = 0.52; p < 0.001), and scaffold diameter (r = 0.74; p < 0.001) in the
      evagination group were positively correlated to the time since scaffold
      implantation. CONCLUSION: Coronary evaginations following BRS implantation are
      associated with an increased scaffold area, indicating that the scaffold follows
      the outward remodeling of the artery. The process affects the entire scaffold
      length and seems to be continuously progressing following implantation.

PMID- 30097189
TI  - Planned use of GP IIb/IIIa inhibitors is safe and effective during implantation
      of the Absorb Bioresorbable Vascular Scaffold.
AB  - Bioresorbable Vascular Scaffolds (BVS) have the potential for adaptive vessel
      remodeling, restoration of vasomotion, and late luminal enlargement, thus
      allowing them to circumvent target lesion failures associated with bare metal
      stents (BMS) and drug-eluting stents (DES). However, recent data has shown a
      concerning increase in BVS-associated scaffold thrombosis (ScT) compared to DES.
      Upfront administration of GP IIb/IIIa inhibitors (GPIs) has shown to reduce early
      stent thrombosis (ST) compared to standard of care in BMS and DES. Since the use
      of GPIs was limited in BVS studies, the effect of GPIs on the rate of BVS
      associated ScT is largely unknown. This is the first study investigating whether
      a planned use of GPIs during implantation of the Absorb BVS represents a safe and
      effective strategy in reducing ScT. In a retrospective chart review of 22
      patients undergoing PCI with BVS implantation and planned GPI administration, no
      acute ScT, in-hospital MACE, or in-hospital major/minor bleeding events were
      observed. Bleeding reduction strategies such as shorter GPI infusion and radial
      access were implemented. This study provides valuable preliminary evidence on the
      benefit and safety in using planned GPI administration to reduce the incidence of
      ScT after implantation of BVS.

PMID- 30097190
TI  - Mother and offspring lateralized social behavior across mammalian species.
AB  - Findings on nonprimate mammals place the issue of mother-infant lateralized
      relations in a broader context, demonstrating that humans are one of many species
      showing this feature. The remarkable interspecies consistency in the direction of
      lateralization points to a continuity between lateralized mother-infant
      interactions in primates and nonprimate mammals and suggests ancient evolutionary
      roots of human cradling bias. The results from species which, in contrast to
      primates, have no direct involvement of forelimbs in mother-infant spatial
      interactions clearly support the perceptual origin of this type of
      lateralization. A right hemisphere advantage for social functions relevant to
      mother-infant interactions is the most probable background for the left-sided
      biases in the behavior of mothers and infants. Recent findings suggest the
      contribution of lateralized mother-infant interactions to biological fitness.
      Mother and infant both can gain advantage from keeping the other on the left
      side.

PMID- 30097191
TI  - Speech lateralization and motor control.
AB  - A relationship between motor control and speech lateralization has long been
      postulated by researchers and clinicians with an interest in the functional
      organization of the human brain. Exactly how motor control might be related to
      speech representation, however, is rarely examined. This chapter examines current
      issues relating to the organization, development, and measurement of motor
      control and speech representation. We further consider from neuropsychological,
      developmental, neurological, and genetic perspectives that speech and fine motor
      control involve planning and sequencing processes, which are mediated by an
      integrated neural network localized to the left hemisphere. Specifically, we
      discuss studies from our laboratory using functional transcranial Doppler
      ultrasonography to determine speech laterality, correlating this with hand
      preference and pegboard measures of motor laterality. Our findings show that
      handedness, as measured by a motor skill task, can be predictive of speech
      laterality, both in typically developing adults and children. We have also shown
      that individuals with developmental motor coordination impairments also show
      atypical speech lateralization, providing further evidence that neurological
      motor and speech systems are intrinsically connected. We consider these results
      in the context of a left-lateralized speech-praxis center model, which could
      account for the relationship shown between sequence-based motor and speech tasks.

PMID- 30097192
TI  - Handedness and cognitive ability: Using meta-analysis to make sense of the data.
AB  - The literature on the relationship between handedness and cognitive ability is
      riddled with studies using different conceptualizations of handedness (e.g., hand
      preference vs hand skill, direction vs degree, consistency vs inconsistency) and
      different conceptualizations of cognitive ability (intelligence vs distinct
      abilities), as well as different measurements thereof. Recently the literature
      was summarized by means of meta-analytic techniques. The findings show quite
      robustly that when handedness is assessed as hand preference and individuals are
      classified according to direction (i.e., as left-handers vs right-handers), no
      differences in cognitive ability emerge between handedness groups. However, other
      evidence points to the importance of assessing degree rather than direction of
      handedness and of employing hand skill rather than hand preference measures. A
      meta-analysis of such studies has not been possible to date, due to their
      scarcity. It is here suggested that degree of handedness and hand skill measures
      are employed in future studies exploring the possible relationship between
      handedness and cognitive ability so as to elaborate whether or not such a
      relationship exists and if so, what its characteristics are.

PMID- 30097193
TI  - Atypical structural and functional motor networks in autism.
AB  - Structural and functional differences between the two cerebral hemispheres
      constitute one of the most fundamental aspects of brain organization. It is well
      established that functions related to language and motor behaviors are more
      strongly represented in the left hemisphere. Individuals with autism spectrum
      disorder (ASD) show impairments particularly in social communication, language,
      and a variety of motor-related symptoms, alongside intact or enhanced right
      hemisphere functions. This pattern of deficits and strengths has given rise to
      theories, suggesting that the neuropathology of ASD involves atypical hemispheric
      specialization. Here, we review the literature on atypical hemispheric
      specialization in the motor domain, which is an understudied field, but one that
      bears great potential for finding meaningful subgroups within the heterogeneous
      autism spectrum. It appears that atypical motor lateralization constitutes a
      candidate neural phenotype of ASD, in being a stable measure across structure,
      function, and behavior.

PMID- 30097194
TI  - Lateralization of the expression of facial emotion in humans.
AB  - Though superficially symmetrical, the human face expresses emotion
      asymmetrically. Darwin (1872) first noted this phenomenon, conceding to being at
      a loss to explain why expressions such as smiling and sneering defiance were
      predominantly one-sided. Emotion lateralization offers a plausible account.
      Because the lower two-thirds of the face is contralaterally controlled, the
      emotion-dominant right hemisphere innervates the lower left hemiface, resulting
      in more intense expressions. Thus whether smiling or sneering, humans show
      stronger emotion on the left side of the face. This chapter reviews research
      examining asymmetries in the expression of facial emotion in humans, commencing
      with discussion of the right hemisphere's dominance for emotion processing. The
      right hemisphere's emotion-processing superiority results in hemifacial
      asymmetries in expressivity: the left hemiface is anatomically more expressive,
      moving more and earlier than the right hemiface. Not surprisingly then, viewers
      are sensitive to the left cheek's greater physiognomic expressivity, perceiving
      the left hemiface as more expressive than the right, even when digitally
      reversed. Critically, human behavior implies an intuitive awareness that the left
      cheek is more emotionally expressive, influencing behaviors including cradling
      infants and posing for photographs. Thus despite the absence of conscious
      awareness, when conveying emotion we intuitively favor the more expressive left
      cheek.

PMID- 30097195
TI  - Split-brain patients: Visual biases for faces.
AB  - Split-brain patients constitute a small subpopulation of epileptic patients who
      have received the surgical resection of the callosal fibers in an attempt to
      reduce the spread of epileptic foci between the cerebral hemispheres. The study
      of callosotomy patients allowed neuropsychologists to investigate the effects of
      the hemispheric disconnection, shedding more light on the perceptual and
      cognitive abilities of each hemisphere in isolation. This view that callosotomy
      completely isolates the hemispheres has now been revised, in favor of the idea of
      a dynamic functional reorganization of the two sides of the brain; however, the
      evidence collected from split-brain patients is still a milestone in the
      neurosciences. The right-hemispheric superiority found in the healthy population
      concerning face perception has been further supported with split-brains, and it
      has been shown that the right disconnected hemisphere appears superior to the
      left hemisphere in recognizing and processing faces with similar characteristics
      as the observers' (e.g., gender, identity, etc.). Even more controversial is the
      field of hemispheric asymmetries for processing facial emotion, some evidence
      suggesting a right-hemispheric superiority for all emotions, some others showing
      a complementary hemispheric asymmetry depending on the positive or negative
      emotional valence. Although the practice of callosotomy is mostly abandoned today
      in favor of pharmacological alternatives, further studies on the remaining split
      brain patients could help advance our understanding of hemispheric specialization
      for social stimuli.

PMID- 30097196
TI  - Manual laterality and cognition through evolution: An archeological perspective.
AB  - To understand the evolution of lateralized motor biases and cognitive functions,
      we rely on archeological methods to give us a window onto the past. Currently,
      the overwhelming majority of prehistoric data on asymmetry and laterality concern
      only the hominin lineage, spanning the time period from the presumed evolutionary
      split with the other great apes around 6-8 million years ago until the present
      day. We present an overview of these data from paleontology and archeology.
      Lateralized motor biases and anatomical asymmetries are evident throughout
      prehistory, showing increases in the predominance of right-handedness over time.
      Laterality was a key feature of the motor-cognitive development of extinct human
      ancestors. However, further research in living humans is needed to resolve the
      extent of colateralization of functions in the human brain, so we urge caution
      when inferring functional cognitive laterality from behavioral markers of
      handedness.

PMID- 30097197
TI  - Insights into the evolution of lateralization from the insects.
AB  - Behavioral lateralization is widespread across the animals, being found in
      numerous vertebrate species as well as in species from across many invertebrate
      phyla. Numerous recent studies have focused on lateralization in the insects,
      exploring the behaviors themselves as well as their neural basis and the possible
      selective pressures that led to their evolution. Lateralization in the insects
      can occur in any sensory modality and may be generated by peripheral or central
      neural asymmetries. The lateralization of particular insect behaviors can show
      either population-level or individual-level lateralization but which of these
      types of lateralization is present is strongly influenced by their social
      environment. Different behaviors from the same species show population-level or
      individual-level lateralization depending on whether these behaviors are used in
      social interactions or not. This has broad implications for our understanding of
      how lateralization and handedness evolves not just in insects but also in
      vertebrates.

PMID- 30097198
TI  - Cognitive archeology, body cognition, and hand-tool interaction.
AB  - Body cognition and lateralization can be investigated in fossils by integrating
      anatomical and functional aspects. Paleoneurology cannot provide strong evidence
      in this sense, because hemispheric asymmetries are shared in all extinct human
      species, and motor cortical areas are difficult to delineate in endocranial
      casts. However, paleoneurological analyses also suggest that modern humans and
      Neanderthals underwent an expansion of parietal regions crucial for visuospatial
      integration and eye-hand-tool management. Because of our technological
      specialization, haptic cognition can be particularly targeted by evolutionary
      processes. Hand-tool relationships can be investigated through physical and
      physiological correlates. In terms of metrics, size is the main factor of hand
      morphological variation among adult humans, followed by the ratio between thumb
      length and palmar size. In modern humans, emotional changes during hand-tool
      contact can be measured by electrodermal activity. During tool manipulation,
      electrodermal response, which is a physiological correlate of emotional
      engagement, shows differences between males and females, and it is different for
      distinct Paleolithic technologies. Emotional engagement, hand management, and
      haptic cognition are part of a specialized prosthetic technological capacity of
      modern humans and can provide indirect evidence of cognitive discontinuities in
      the archeological record.

PMID- 30097199
TI  - Motor asymmetries in fishes, amphibians, and reptiles.
AB  - The study of brain and behavioral lateralization in so-called "lower vertebrates"
      (fish, amphibians, and reptiles) has received increasing attention in the last
      years, in an attempt to understand its phylogenetic origins and evolutionary
      significance. Observations on the earliest tetrapods, the amphibians, have helped
      us to understand the evolution of limb preference and suggest that laterality
      could have appeared even prior to the evolution of tetrapods. Insights into
      lateralized behaviors in fish-such as the turning behavior-have had an important
      role in uncovering proximate and ultimate causes of motor lateralization in the
      vertebrate subphylum. Additionally, investigations on the alignment of behavioral
      preferences in fish populations have helped do develop formal models to explain
      the unequal distribution of left- and right-lateralized individuals as the result
      of evolutionarily stable strategies among lateralized asymmetric individuals that
      interact cooperatively or competitively.

PMID- 30097200
TI  - Evolution and development of handedness: An Evo-Devo approach.
AB  - Hand preference is a sensorimotor skill whose development both reflects and
      promotes the development of hemispheric lateralization for manual and cognitive
      functions. Extensive comparative, crosscultural, and paleoanthropological
      evidence demonstrates the prevalence of limb lateralized preferences across
      vertebrate species and the prevalence of right-handedness within hominid
      evolution. Many reviews of the evolution and development of human handedness have
      proposed adaptive explanations for its evolution. However, during the last 3
      decades a new approach to understanding evolution (the Extended Evolutionary
      Synthesis-EES) provided a persuasive alternative to the conventional (Neo
      Darwinian Synthetic Theory-ST) evolutionary and developmental accounts. EES
      combines modern evolutionary and developmental research (Evo-Devo) in ways that
      alter understanding of natural selection, adaptation, and the role of genes in
      development and evolution. These changes make obsolete all past accounts of the
      evolution and development of lateralization and handedness because EES/Evo-Devo
      requires new study designs. The developmental trajectories of any structural or
      functional trait must be specified so that it may be related to variations in the
      developmental trajectories of other traits. First, we describe how the EES/Evo
      Devo differs from the conventional ST, particularly for understanding of how
      traits develop. Then, we apply Evo-Devo to the study of handedness development in
      infancy and its relation to the development of other cognitive functions.
      Finally, we argue that identifying the development of atypical traits would
      benefit from knowledge of the range of individual differences in typical
      developmental trajectories of hand-use preference and their relation to
      variations in the developmental trajectories of cognitive functions.

PMID- 30097201
TI  - A comparative perspective on lateral biases and social behavior.
AB  - Cerebral lateralization and associated motor behaviors were historically thought
      to be characteristics unique to humans. Today, it is clear that these features
      are present and visible in other animal species. These shared attributes of brain
      and behavior suggest inheritance from a distant common ancestor. Population-level
      motor biases are likely to reflect an early evolutionary division of primary
      survival functions of the brain's left and right hemispheres. In modern humans,
      these features may provide a foundational platform for the development of higher
      cognitive functions, inextricably cementing the ties between the evolution and
      development of cognition. This chapter focuses on the links between a vertebrate
      wide right hemisphere dominance for perceiving and producing social signals, left
      side motor biases (inclusive of visual field preferences), and the evolution and
      development of cognition in modern humans.

PMID- 30097202
TI  - Sensorimotor lateralization scaffolds cognitive specialization.
AB  - In this chapter, we review hemispheric differences for sensorimotor function and
      cognitive abilities. Specifically, we examine the left-hemisphere specialization
      for visuomotor control and its interplay with language, executive function, and
      musical training. Similarly, we discuss right-hemisphere lateralization for
      haptic processing and its relationship to spatial and numerical processing. We
      propose that cerebral lateralization for sensorimotor functions served as a
      foundation for the development of higher cognitive abilities and their
      hemispheric functional specialization. We further suggest that sensorimotor and
      cognitive functions are inextricably linked. Based on the studies discussed in
      this chapter our view is that sensorimotor control serves as a loom upon which
      the fibers of language, executive function, spatial, and numerical processing are
      woven together to create the fabric of cognition.

PMID- 30097203
TI  - A review of performance asymmetries in hand skill in nonhuman primates with a
      special emphasis on chimpanzees.
AB  - Most humans report preferring the right hand for a variety of manual actions.
      Additionally, most humans perform motor tasks better with their right hand,
      particularly among right-handed individuals, but less so among left-handed
      people. Some have suggested that asymmetries in performance rather than hand
      preference may better reflect left hemisphere specializations in motor functions.
      In contrast to humans, research on performance asymmetries in manual tasks by
      nonhuman primates has received far less empirical investigation. In this chapter,
      I review the evidence presented to date on individual- and population-level
      asymmetries in motor tasks in nonhuman primates. Broadly speaking, studies on
      motor asymmetries have focused on (1) intermanual differences in grasping
      morphology and (2) intermanual differences in performance on a variety of
      different motor tasks. The results suggest that some species show population
      level left-right differences in motor skill. Moreover, performance differences
      between the left and right hands appear to be mediated by preferred hand use but
      not in a dissociative manner. The collective data suggest that measures of
      performance asymmetries in different primate species may provide additional
      insight into theories on the evolution of hemispheric specialization in motor
      control.

PMID- 30097204
TI  - Manual bias, behavior, and cognition in common marmosets and other primates.
AB  - This chapter examines the importance of studying hand preference together with
      different expressions of behavior. Cognitive differences between left- and right
      handed primates are discussed. As shown in several species of primate, eye
      preference, but not hand preference, is biased at the level of the population and
      reflects hemispheric asymmetry of processing. Hand preference, determined from
      simple grasping of pieces of food and taking them to the mouth, is consistent for
      individuals but it is not population biased. It is a measure of an individual's
      preference to use a particular hemisphere, and hence which cognitive processes
      are characteristic of the individual. Compared to left-handed subjects, right
      handed subjects are more active in exploring novel objects, show more social
      facilitation of behavior, have a positive cognitive bias, and express lower
      levels of fear and stress responses. In marmosets, learning of food searching
      tasks is not associated with hand preference. Strength of hand preference, rather
      than its direction, is linked to the ability to perform two tasks at once, viz.,
      detection of a predator while searching for food. Marmosets with strong hand
      preferences are able to perform these two tasks at once but those with weak or no
      hand preference are unable to do so.

PMID- 30097205
TI  - Introduction.

PMID- 30097206
TI  - Adenovirus infection-A rare cause of interstitial nephritis in kidney transplant.

PMID- 30097207
TI  - Multiple lymphangiohemangiomas with thoracic and abdominal involvement: a case
      report.
AB  - We present a case of multiple lymphangiohemangiomas (hematolymphangiomas,
      hemangiolymphangiomas, or combined lymphatic venous malformation) with thoracic
      and abdominal involvement in an asymptomatic patient. We describe and illustrate
      the imaging findings in this disease, which are quite characteristic and can
      enable an accurate diagnosis. To our knowledge, there are no other reports of
      similar cases in the scientific literature.

PMID- 30097208
TI  - A Sticky Situation: Meconium Aspiration in the Emergency Department.

PMID- 30097209
TI  - A caregiver educational program: A video program to promote aging services
      technologies awareness.
AB  - Research demonstrated that aging services technologies (ASTs) can reduce
      caregiver burden. However, ASTs are underutilized by caregivers due to poor
      awareness. This study evaluated the effectiveness of a video-based educational
      program to increase caregiver AST knowledge among 43 caregivers. Paired sample t
      tests showed positive change in AST knowledge, stigma, and intention to engage in
      AST activities post-program. Caregivers endorsed highly positive AST views pre-
      and post-program without statistically significant change. Group by time repeated
      measures ANOVAs showed younger caregivers (<65 years old) had better knowledge
      and were more open to ASTs (improved attitude and stigma scores) than older
      caregivers (>65 years old). A significant interaction revealed caregivers of
      individuals who had fewer, but not more, domains of functional limitation
      reported a positive change in AST attitude post-program. The video program
      appeared to be beneficial to all caregivers, who provided vastly positive program
      feedback.

PMID- 30097210
TI  - [Dermatofibroma with sebaceous induction].
AB  - BACKGROUND: Histiocytoma or dermatofibroma (DF) is a common benign skin tumour
      with several clinical and histopathological variants. Sebaceous induction
      overlying a dermatofibroma is rare and infrequently reported. Using a detailed
      clinical case, herein the semiological and dermoscopic features of this lesion
      are described and illustrated, and the differential diagnoses presented. PATIENTS
      AND METHODS: A 52-year-old man consulted for a physical examination, which
      revealed a firm papular lesion of the upper middle back. The upper part of the
      nodule was covered by a slightly hyperpigmented surface, with numerous small
      whitish lobules. Microscopic examination revealed a dermatofibroma with sebaceous
      induction. DISCUSSION: Sebaceous induction overlying a dermatofibroma is not
      frequent, and it occurs in most cases on or near the shoulder. The typical
      dermoscopic pattern involves many whitish globules or clumps grouped into
      clusters. The aetiology is unknown but could stem from a conducive
      microenvironment in shoulder skin, associated with growth factors secreted by the
      DF.

PMID- 30097211
TI  - [Bullous pemphigoid localised to a strip of skin].

PMID- 30097212
TI  - Promoter mutation in long non-coding RNA NEAT1 is not common in common solid
      cancers.

PMID- 30097214
TI  - Bioinformatics analysis of gene expression profiles to diagnose crucial and novel
      genes in glioblastoma multiform.
AB  - Therefore, the current study aimed to diagnose the genes associated in the
      pathogenesis of GBM. The differentially expressed genes (DEGs) were diagnosed
      using the limma software package. The ToppFun was used to perform pathway and
      Gene Ontology (GO) enrichment analysis of the DEGs. Protein-protein interaction
      (PPI) networks, extracted modules, miRNA-target genes regulatory network and
      miRNA-target genes regulatory network were used to obtain insight into the
      actions of DEGs. Survival analysis for DEGs carried out. A total of 701 DEGs,
      including 413 upregulated and 288 downregulated genes, were diagnosed between
      U1118MG cell line (PK 11195 treated with 1 h exposure) and U1118MG cell line (PK
      11195 treated with 24 h exposure). The up-regulated genes were enriched in
      superpathway of pyrimidine deoxyribonucleotides de novo biosynthesis, cell cycle,
      cell cycle process and chromosome. The down-regulated genes were enriched in
      folate transformations I, biosynthesis of amino acids, cellular amino acid
      metabolic process and vacuolar membrane. The current study screened the genes in
      PPI network, extracted modules, miRNA-target genes regulatory network and miRNA
      target genes regulatory network with higher degrees as hub genes, which included
      MYC, TERF2IP, CDK1, EEF1G, TXNIP, SLC1A5, RGS4 and IER5L Survival suggested that
      low expressed NR4A2, SLC7 A5, CYR61 and ID1 in patients with GBM was linked with
      a positive prognosis for overall survival. In conclusion, the current study could
      improve our understanding of the molecular mechanisms in the progression of GBM,
      and these crucial as well as new molecular markers might be used as therapeutic
      targets for GBM.

PMID- 30097215
TI  - Clonal evolution of myelofibrosis treated with hematopoietic transplantation,
      using RUXOLITINIB for chronic GvHD: A case report.
AB  - Deciphering the mutational patterns and/or the biomarkers that might predict
      clinical response in patients with myelofibrosis is primordial to make treatment
      decisions. In this report, we discuss the clinical history, pathological
      evaluation, and genomics findings in a patient with JAK2-positive myelofibrosis
      who developed a secondary myelodysplasia after hematopoietic stem cell
      transplantation and JAK1/2 inhibitor treatment. Using next-generation sequencing,
      a paired comparison of relapse-specific versus primary tumour mutations
      highlighted the dynamic clonal evolution at relapse, showing concurrently the
      complete eradication of the JAK2-positive clone and the expansion of a second
      JAK2-negative clone with additional mutations. Importantly, another unexpected
      finding was that myelodysplasia was not secondary to allogeneic transplantation
      as relapse was driven by the overgrowth of a preexisting mutated clone, probably
      fostered by initial treatment options. This case underlines the fact that
      determining the genetic changes associated with the primary disease and its
      evolution is crucial to accurately correlate variants frequency to treatment
      decision and/or treatment response.

PMID- 30097213
TI  - Alkaline ceramidase 3 promotes growth of hepatocellular carcinoma cells via
      regulating S1P/S1PR2/PI3K/AKT signaling.
AB  - OBJECTIVE: Hepatocellular carcinoma (HCC) is one of the cancer types with poor
      prognosis. To effectively treat HCC, new molecular targets and therapeutic
      approaches must be identified. Alkaline ceramidase 3 (Acer3) hydrolyzed long
      chain unsaturated ceramide to produce free fatty acids and sphingosine. However,
      whether and how Acer3 modulates progression of HCC remains largely unknown.
      METHODS: Acer3 mRNA levels in different types of human HCC samples or normal
      tissues were determined from Gene Expression across Normal and Tumor tissue
      (GENT) database. The expression level of Acer3 in human HCC cell lines were
      examined by western blot. Overall survival and disease-free survival of HCC
      patients were determined by Kaplan-Meier analysis. Effects of Acer3 knockdown by
      lentivirus infection were evaluated on cell growth and apoptosis. The mechanisms
      involved in HCC cells growth and apoptosis were analyzed by western blot.
      RESULTS: In silico analysis of TCGA databases of HCC patients showed that the
      expression of Acer3 significantly inversely correlates with the overall and
      disease-free survival of HCC patients. Knockdown expression of Acer3 resulted in
      decreased cell growth and increased apoptosis. Notably, inhibition of Acer3
      resulted in intracellular exhaustion of Sphingosine-1-phosphate (S1P) and
      inhibited activation of S1PR2/PI3K/AKT signaling. Finally, knockdown of Acer3
      induced up-regulation of Bax and down-regulation of Bcl-2. CONCLUSIONS: Our study
      suggests that Acer3 contributes to HCC propagation, and suggests that inhibition
      of Acer3 may be novel strategy for treating human HCC.

PMID- 30097216
TI  - Hyponatraemia during an emergency medical admission as a marker of illness
      severity & case complexity.
AB  - BACKGROUND: Altered sodium balance at time of an emergency medical admission
      adversely impacts on outcome; whether hyponatraemia is independently associated
      with outcomes or a surrogate of acute illness severity has been debated. METHODS:
      All emergency medical admissions between 2002 and 2017 were studied and a risk
      score calculated. We compared univarate deciles of admission sodium using a
      multivariable model, adjusting for risk score. RESULTS: There were 106,586
      admissions in 54,928 patients. Patients with lower sodium at admission were older
      at 66.7 years (IQR 46.7-79.5) compared with 63.3 years (IQR 42.9-78.2) with a
      longer length of stay (LOS) of 6.8 days (IQR 3.0-14.7) versus 4.9 days (IQR 1.8
      10.9). They had a higher 30-day in-hospital mortality at 6.4% vs 4.4% (p <
      0.001). Admission sodium predicted survival - OR 0.89 (95%CI 0.88-0.90). We
      adjusted the model with a Risk Score that is predictive and exponentially related
      to 30-day in-hospital mortality. When adjusted for Risk Score, the admission
      sodium value was less predictive - OR 0.95 (95%CI 0.92-0.97). The cumulative
      percentages within the lowest five deciles fell from 63.3% between 2002 and 2009
      to 48.1% from 2010 to 2017. The slope of the prediction line relating admission
      sodium to mortality did not change over time but a lower mortality rate was
      predicted at any given sodium level. CONCLUSION: Hyponatraemia at the time of an
      emergency medical admission is predictive and probably a marker of Acuity Illness
      Severity and Case Complexity. Both the frequency of abnormality in admission
      sodium and mortality have fallen over time.

PMID- 30097217
TI  - Corrigendum to "Antithrombotic therapy trends in non-valvular atrial fibrillation
      patients undergoing percutaneous coronary stent implantation: Results from a
      survey among fellows at the Japanese College of Cardiology" [J. Cardiol. 72 (2)
      (2018) 113-119].

PMID- 30097218
TI  - WASP (Write a Scientific Paper): Critical appraisal of existing research.
AB  - Critical appraisal of research involves a systematic process which assesses the
      question/s posed, study design and execution, statistical evaluation,
      interpretation of the results, and appropriateness of the conclusions. It
      necessitates identification of conflicts of interest, analyses the strengths and
      weaknesses of the study and ultimately the validity, reliability and relevance of
      the reported findings.

PMID- 30097219
TI  - Innovative approaches to track lymph node germinal center responses to evaluate
      development of broadly neutralizing antibodies in human HIV vaccine trials.
AB  - Phase 1 clinical studies will soon evaluate novel HIV-1 envelope immunogens
      targeting distinct 'germline' and memory B cell receptors to ultimately elicit
      HIV-1 broadly neutralizing antibodies (bNAbs). The National Institute of Allergy
      and Infectious Diseases (NIAID) recently convened a panel of US-based expert
      scientists, clinicians, sponsors and ethicists to discuss the role of sampling
      draining lymph nodes within preventive HIV vaccine trials. The meeting addressed
      the importance of evaluating germinal center (GC) responses following
      immunization to predict bNAb potency and breadth, and reviewed key aspects of
      this procedure within the clinical research setting, including informed consent,
      adverse event monitoring, study participant acceptability, medical expertise and
      training. We review highlights from the meeting and discuss the advantages and
      disadvantages of sampling lymph nodes by excisional biopsies compared to fine
      needle aspirations (FNA) in the context of prophylactic HIV vaccine trials.

PMID- 30097221
TI  - Desmoplastic fibroma of bone arising in the cortex of the proximal femur.

PMID- 30097220
TI  - Induction and maintenance of a phenotypically heterogeneous lung tissue-resident
      CD4+ T cell population following BCG immunisation.
AB  - Tuberculosis (TB) is the biggest cause of human mortality from an infectious
      disease. The only vaccine currently available, bacille Calmette-Guerin (BCG),
      demonstrates some protection against disseminated disease in childhood but very
      variable efficacy against pulmonary disease in adults. A greater understanding of
      protective host immune responses is required in order to aid the development of
      improved vaccines. Tissue-resident memory T cells (TRM) are a recently-identified
      subset of T cells which may represent an important component of protective
      immunity to TB. Here, we demonstrate that intradermal BCG vaccination induces a
      population of antigen-specific CD4+ T cells within the lung parenchyma which
      persist for >12 months post-vaccination. Comprehensive flow cytometric analysis
      reveals this population is phenotypically and functionally heterogeneous, and
      shares characteristics with lung vascular and splenic CD4+ T cells. This
      underlines the importance of utilising the intravascular staining technique for
      definitive identification of tissue-resident T cells, and also suggests that
      these anatomically distinct cellular subsets are not necessarily permanently
      resident within a particular tissue compartment but can migrate between
      compartments. This lung parenchymal population merits further investigation as a
      critical component of a protective immune response against Mycobacterium
      tuberculosis (M. tb).

PMID- 30097223
TI  - Red Blood Cell Alloimmunization in the Pregnant Patient.
AB  - Alloimmunization to red blood cell (RBC) antigens represents a challenge for
      physicians caring for women of child bearing potential. Exposure to non-self RBC
      antigens may occur during transfusion or pregnancy leading to the development of
      antibodies. If a subsequent fetus bears that antigen, maternal antibodies may
      attack the fetal red blood cells causing red cell destruction and clinically
      significant hemolytic disease of the fetus and newborn (HDFN). In the most severe
      cases, HDFN may result in intrauterine fetal demise due to high output cardiac
      failure, effusions and ascites, known as "hydrops fetalis". This article reviews
      strategies for management and prevention of RBC alloimmunization in women of
      child bearing potential.

PMID- 30097222
TI  - Effects of bone morphogenic protein-2 loaded on the 3D-printed MesoCS scaffolds.
AB  - BACKGROUND/PURPOSE: The mesoporous calcium silicate (MesoCS) 3D-printed scaffold
      show excellent bioactivity and can enhance the bone-like apatite formation. The
      purpose of this study aims to consider the effects of the different loading
      methods on the novel grafting materials which composed of bone morphogenetic
      protein-2 (BMP-2) loaded MesoCS scaffold by employing 3D-printing technique.
      METHODS: The MesoCS scaffold were fabricated by fused deposition modeling. In
      this study, there are two methods of loading BMP-2: (1) the pre-loading (PL)
      method by mixing MesoCS and BMP-2 as a raw material for a 3D-printer, and (2) the
      direct-loading (DL) method by soaking the 3D-printed MesoCS scaffold in a BMP-2
      solution. The characteristics of MesoCS scaffold were examined by transmission
      electron microscopy (TEM), X-ray diffraction (XRD) and scanning electron
      microscopy (SEM). Their physical properties, biocompatibility, and osteogenic
      related ability were also evaluated. RESULTS: The 3D MesoCS/PCL scaffolds showed
      excellent biocompatibility and physical properties. After soaking in simulated
      body fluid, the bone-like apatite layer of the PL and DL groups could be formed.
      In addition, the DL group released fifty percent more than the PL group at the
      end of the first day and PL showed a sustained release profile after 2 weeks.
      CONCLUSION: The 3D MesoCS/PCL porous scaffolds were successfully fabricated via a
      3D printing system and were tested in vitro and were found to show good cellular
      activity for cell behavior although the PL method was not favorable for clinical
      application in relation with the preservation of BMP-2. With regards to different
      growth factor loading methods, this study demonstrated that PL of BMP-2 into
      MesoCS prior to printing will result in a more sustained drug release pattern as
      compared to traditional methods of scaffolds directly immersed with BMP-2.

PMID- 30097224
TI  - Inherited Bleeding Disorders in the Obstetric Patient.
AB  - Inherited bleeding disorders increase the risk of bleeding in the obstetric
      patient. Randomized controlled trials to compare prophylactic or therapeutic
      interventions are rare, and guidance documents rely heavily on expert opinion.
      Here we report the results of a systematic review of the literature for the
      treatment and prevention of peripartum bleeding in women with an inherited
      bleeding disorder. The highest-quality evidence is for the use of tranexamic acid
      in postpartum hemorrhage, which has been shown to decrease bleeding-related
      mortality in women without bleeding disorders. There is limited evidence for
      prophylactic use of this agent in women with inherited bleeding disorders.
      Desmopressin has also been used in observational studies of patients with von
      Willebrand disease and carriers of hemophilia A with some success, although
      concerns about the risk of hyponatremia persist. In patients with deficiencies of
      specific factors, replacement is generally the preferred approach, and
      concentrates have been studied in deficiencies of VWF and factors VII, VIII, IX,
      XI, and XIII as well as in patients with fibrinogen deficiency. Because of the
      small size of these studies, neither safety nor efficacy is well established,
      although the literature suggests that bleeding history may be more predictive of
      outcomes than factor levels in many cases. Goal factor levels have not been
      studied or systematically established in any of these diseases, although
      observational data suggest that achieving normal levels may be inadequate,
      particularly for VWF and factor VIII, which are physiologically elevated in
      pregnancy. For factor deficiencies in which no specific concentrate is available,
      such as factors II (prothrombin) and V, prothrombin complex concentrate or fresh
      frozen plasma may be used, and for platelet defects or deficiencies, such as
      Glanzmann thrombasthenia or Bernard-Soulier syndrome, platelet transfusion is
      generally first line, although use of recombinant FVIIa has been reported in
      patients with Glanzmann thrombasthenia to avoid development of, or treat patients
      with, antibodies to platelet glycoprotein IIbIIIa. Ultimately, data are lacking
      to definitively support an evidence-based approach to management in any of these
      disorders, and prospective, controlled studies are desperately needed.

PMID- 30097225
TI  - The implication of Numb-induced Notch signaling in endothelial-mesenchymal
      transition of diabetic nephropathy.
AB  - AIM: This study was purposed to figure out the contribution of Numb-induced Notch
      signaling to the development of diabetic nephropathy (DN). METHODS: Two hundred
      and twenty six DN patients were included, and human glomerular endothelial cells
      (RGEC) were cultured. MSCV-Numb-IRES-GFP, MSCV-Notch1-IRES-GFP and MSCV-Hes1-IRES
      GFP were transfected to construct the recombinant retroviral vectors. RESULT: The
      over-expressed Numb and Notch1, as well as the under-expressed Hes-1 were
      correlated with the undesirable prognosis of DN patients (P < 0.05). Within the
      cell lines transfection with si-Numb would cut down E-cadherin and CD31
      expressions (P < 0.05), yet elevated alpha-SMA and vimentin expressions (P <
      0.05). The apoptotic rate of si-Numb cell lines underperformed ones categorized
      into the hyperglucose group (P < 0.05), whereas the lowly-expressed Notch1 and
      Hes1 were observably associated with inhibited proliferation of myofibroblasts (P
      < 0.05). Addition of ADPT caused under-expressed alpha-SMA and vimentin, along
      with the over-expressed E-cadherin and CD31 (P < 0.05). Silencing of Notch1 and
      Hes1 reversed the epithelial-mesenchymal transition (EMT) process that was
      triggered by high glucose (P < 0.05). CONCLUSION: Numb negatively regulated Notch
      signaling pathway in EMT of DN, implying that they had great potentials to serve
      as therapeutic targets or diagnostic biomarkers for DN.

PMID- 30097226
TI  - The dosimetric differences in calculating lung SBRT plans on different image data
      sets: Comparison of the free breathing scan to both the average intensity
      projection scan and to the sum of calculations on each respiratory phase of the
      4DCT scan.
AB  - The purpose of this study is to evaluate the dosimetric differences to the lung
      internal target volume (ITV) in stereotactic body radiation therapy (SBRT) when
      calculated on the free breathing (FB) scan in comparison to calculations on the
      average intensity projection (AIP) scan as well as the sum of dose calculated on
      each of the treated respiratory phases. The clinical treatment plan data for 16
      SBRT lung patients were retrospectively chosen for this study, 5 of which were
      30% to 70% respiratory phase gated. All patients had ITV contours and fixed
      monitor units from the treatment approved plan copied over to each scan on which
      calculations were to be made. The results of this study yielded 6 out of 16
      patients with greater than or equal to 2% difference in ITV maximum dose (D0) and
      2 of 16 patients with greater than or equal to 2% difference in ITV minimum dose
      (D100). The range of ITV dose differences for these 8 patients was 2% to 4.7%
      with no patients exceeding a 5% difference in D0 or D100. None of the patients
      had greater than or equal to 2% difference in ITV mean dose (Dmean). Sixty-three
      percent of patients with greater than 2% ITV dose difference in any of the
      categories reviewed were those patients with greater than 1 cm gross tumor
      motion. This study concluded that in order to reduce uncertainty in dose to the
      ITV, tumor motion should be assessed at simulation and limited to below 1 cm in
      any direction if possible.

PMID- 30097227
TI  - Pharmacokinetics variability: Why nanoparticles are not just magic-bullets in
      oncology.
AB  - Developing nanoparticles to improve the specificity of anticancer agents towards
      tumor tissue and to better control drug delivery is a rising strategy in
      oncology. An increasing number of forms (e.g., conjugated nanoparticles,
      liposomes, immunoliposomes...) are now available on the shelves and numerous
      other scaffolds (e.g., dendrimeres, nanospheres, squalenes ...) are currently at
      various stages of development. However, as of today most nanoparticles made
      available remain lipidic carriers. Pharmacokinetic variability is a major, yet
      largely underestimated issue with liposomal nanoparticles. A wide variety of
      causes (e.g., tumor type and disease staging, comorbidities, patient's immune
      system) can explain this variability, which can in return negatively impact
      pharmacodynamic endpoints such as poor efficacy or severe toxicities. This review
      aims to cover the main causes for erratic pharmacokinetics observed with most
      nanoparticles, especially liposomes used in oncology. Should the main causes of
      such variability be identified, specific studies in non-clinical or clinical
      development stages could be undertaken using dedicated models (i.e., mechanistic
      or semi-mechanistic mathematical models such as PBPK approaches) to better
      describe nanoparticles pharmacokinetics and decipher PK/PD relationships. In
      addition, identifying relevant biomarkers or parameters likely to impact
      nanoparticles pharmacokinetics would allow for either the modification of their
      characteristics to reduce the influence of the expected variability during
      development phases or the development of biomarker-based adaptive dosing
      strategies to maintain an optimal efficacy/toxicity balance. Broadly, we call for
      the development of comprehensive distribution studies and state-of-the-art
      modeling support to better understand and anticipate nanoparticle
      pharmacokinetics in oncology.

PMID- 30097228
TI  - Pharmacokinetic variability of anticoagulants in patients with cancer-associated
      thrombosis: Clinical consequences.
AB  - The use of anticoagulants in patients with cancer is challenging as several co
      morbidities modifying pharmacokinetic (PK) parameters and significant drug-drug
      interactions with concomitant anti-neoplastic therapies may lead to PK
      variability resulting in increased risk of thrombosis or bleeding. Data on the
      management of patients with cancer-associated thrombosis (CAT) in real life are
      scarce since patients with cancer presenting with significant comorbidities tend
      to be excluded from large trials. This review is mostly based on case-reports and
      pharmacokinetics in an attempt to provide oncologists, with relevant orientation
      based on our best knowledge to date. Overall, low-molecular-weight heparins
      (LMWH) are the preferred option for the long-term prophylaxis and treatment of
      CAT as their benefit-risk was shown superior to vitamin K antagonists (VKA).
      Direct oral anticoagulants (DOAC) may represent an alternative to LMWH provided
      that a favorable benefit-risk in patients with CAT is evidenced in the future. We
      recommend a systematic risk-assessment including body composition, multiple
      medication, and renal function. Moreover a systematic and early discussion
      between pharmacist and oncologist should optimize the benefit-risk ratio for each
      patient.

PMID- 30097229
TI  - Anthropometric factors and non-Hodgkin's lymphoma risk: systematic review and
      meta-analysis of prospective studies.
AB  - The associations between anthropometric factors and non-Hodgkin's lymphoma (NHL)
      risk remain inconclusive. A meta-analysis was performed to clarify these
      associations. PubMed and Web of Science were searched for relevant prospective
      observational studies. A random-effects model was used to generate the summary
      relative risks (RRs) with 95% confidence intervals (CIs). A total of 22
      prospective cohort studies, with over 20,000 NHL cases, were included in the
      present meta-analysis. The summary RRs of NHL risk were 1.06 (95% CI 1.03, 1.09)
      for each 5 kg/m2 increase in body mass index (BMI), 1.11 (95% CI 1.07, 1.16) for
      each 5 kg/m2 increase in BMI in early adulthood (age 18-21 years), 1.05 (95% CI
      1.01, 1.09) for each 10 kg increase in weight, 1.21 (95% CI 1.15, 1.28) for each
      10 kg increase in weight in early adulthood (age 18-21 years), and 1.13 (95% CI
      1.10, 1.17) for each 10 cm increase in height. No association was found for waist
      circumference (WC) and waist-to-hip ratio. By subtypes, all anthropometric
      factors (but not WC) were associated with an increased risk of diffuse large B
      cell lymphoma. Chronic lymphocytic leukemia/small lymphocytic lymphoma was
      positively associated with BMI in early adulthood and with height, whereas
      follicular lymphoma was only positively associated with height. In summary, BMI
      and weight in early adulthood may be more relevant to NHL development than
      current BMI and weight. These findings emphasize the importance of maintaining a
      healthy weight throughout the life-course, starting from early life, for NHL
      prevention. Increased NHL risk with taller stature, which may reflect cumulative
      exposure to hormones/growth factors and nutrition status in early life, further
      supports the relevance of early life exposure in the etiology of NHL.

PMID- 30097230
TI  - Immune-checkpoint inhibitors in previously treated patients with advanced or
      metastatic urothelial carcinoma: A systematic review and meta-analysis.
AB  - Immunotherapy represents a new hope for patients with advanced urothelial
      carcinoma (UC). However, to date, only one of two randomized studies showed a
      clear survival advantage with these treatments. Aimed to investigate the role of
      immune-checkpoint inhibitors in patients with platinum progressed metastatic UC
      we performed a systematic review and meta-analysis of clinical trials to evaluate
      the efficacy and activity, in terms of Overall Survival (OS) and Objective
      Response Rate (ORR). Immune checkpoint inhibitors have showed to improve OS
      compared to chemotherapy in unselected patients (HR 0.80, 95% CI 0.69-0.93, p =
      0.003), while the difference was not significant in patients selected for PD-L1
      expression (HR 0.72, 95% CI 0.48-1.09, p = 0.12). Pooled probability of response
      was 0.18 (95% CI 0.16-0.20) in unselected patients and 0.27 (95% CI 0.25-0.32) in
      PD-L1 selected patients. Immunotherapy results in a significant survival
      advantage in PD-L1 unselected patients suggesting that PD-L1 expression may not
      be a reliable marker in previously platinum treated patients.

PMID- 30097231
TI  - Ionizing radiation-induced cellular senescence promotes tissue fibrosis after
      radiotherapy. A review.
AB  - Ionizing radiation-exposure induces a variety of cellular reactions, such as
      senescence and apoptosis. Senescence is a permanent arrest state of the cell
      division, which can be beneficial or detrimental for normal tissue via an
      inflammatory response and senescence-associated secretion phenotype. Damage to
      healthy cells and their microenvironment is considered as an important source of
      early and late complications with an increased risk of morbidity in patients
      after radiotherapy (RT). In addition, the benefit/risk ratio may depend on the
      radiation technique/dose used for cancer eradication and the irradiated volume of
      healthy tissues. For radiation-induced fibrosis risk, the knowledge of mechanisms
      and potential prevention has become a crucial point to determining radiation
      parameters and patients' intrinsic radiosensitivity. This review summarizes our
      understanding of ionizing radiation-induced senescent cell in fibrogenesis. This
      mechanism may provide new insights for therapeutic modalities for better
      risk/benefit ratios after RT in the new era of personalized treatments.

PMID- 30097232
TI  - Concern over cost of and access to cancer treatments: A meta-narrative review of
      nivolumab and pembrolizumab studies.
AB  - BACKGROUND: A better understanding of the modulation of the immune system has
      resulted in the development of new classes of antitumor agents such as nivolumab
      and pembrolizumab. Despite the proven effectiveness and tolerability of these new
      drugs for specific types of cancer, the high cost of treatment has affected their
      accessibility. OBJECTIVE: The aim of this study is to conduct a meta-narrative
      review of studies that have addressed the concerns that have been voiced
      regarding the cost of and access to nivolumab and pembrolizumab in oncology
      health care. This meta-narrative review attempts to answer the following
      questions: (1) which papers have considered this broad topic area?; (2) what are
      the main empirical/theoretical findings?; and (3) what insights can be drawn by
      combining and comparing findings from different papers? METHODS AND DATA SOURCE:
      A meta-narrative review has been conducted in 5 research databases (Web of
      Science, Science Direct, Scopus, Embase and Pubmed) without time limitations up
      to January of 2017 to address concerns related to the cost of and access to
      nivolumab and pembrolizumab in oncology health care. From each research base,
      articles were selected that had a key word related to the theme of
      pharmacoeconomics and nivolumab or pembrolizumab in any field of scientific work.
      The research questions were analyzed through the application of a meta-narrative
      review approach and the use of a convergence-coding matrix to summarize
      similarities and differences directly related to the research topic between the
      different papers. KEY FINDINGS: The first contribution of this meta-narrative
      review is that it summarizes economic-based works on the use of nivolumab and
      pembrolizumab, particularly for three therapeutic indications: melanoma, NSCLC
      and RCC. In general, despite the clinical benefit of nivolumab and pembrolizumab
      being well accepted and proven by scientific works, the published studies show
      that there are contradictory results with regard to the cost-effectiveness of
      these anti-PD-1s. The regulatory, economic and epidemiological variations mean
      that healthcare costs for cancer patients vary greatly from country to country
      and according to the type of tumor. The second contribution has to do with the
      recommendations for the development of high quality process for pharmacoeconomic
      analyses, especially in the new field of immuno-oncology. Finally, the third
      contribution is with regard to recommendations for the sustainable use of
      immunotherapies. CONCLUSIONS: Given the revolution in cancer therapy in recent
      years, the efficient allocation of existing resources is essential for healthcare
      systems to meet the evolving needs of populations and remain sustainable in the
      long term. The application of high quality information that stems from scientific
      evidence and economic modeling can help considerably to make the healthcare
      system sustainable over time mainly due to a higher number of therapeutic
      indications or more countries giving regulatory approval for the use of new and
      expensive cancer drugs.

PMID- 30097233
TI  - Critical review of axillary recurrence in early breast cancer.
AB  - Around 2% of early breast cancer cases treated with axillary lymph node
      dissection (ALND) underwent axillary recurrence (AR) and it has a deleterious
      effect in prognosis. Different scenarios have incorporated Sentinel Lymph Node
      (SLN) Biopsy (SLNB) instead of ALND as part of the standard treatment and more
      effective systemic treatment has also been incorporated in routine management
      after first curative surgery and after regional recurrence. However, there is
      concern about the effect of SLNB alone over AR risk and how to predict and treat
      AR. SLN biopsy (SLNB) has been largely accepted as a valid option for SLN
      negative cases, and recent prospective studies have demonstrated that it is also
      safe for some SLN-positive cases and both scenarios carry low AR rates. Different
      studies have identified clinicopathological factors related to aggressiveness as
      well as high-risk molecular signatures can predict the development of
      locoregional recurrence. Other publications have evaluated factors affecting
      prognosis after AR and find that time between initial treatment and AR as well as
      tumor aggressive behavior influence patient survival. Retrospective and
      prospective studies indicate that treatment of AR should include local and
      systemic treatment for a limited time.

PMID- 30097234
TI  - Imaging predictors of treatment outcomes in rectal cancer: An overview.
AB  - The treatment protocols for rectal cancer continue to evolve, with increasing
      acceptance of a watch-and-wait policy for clinical complete responders to
      neoadjuvant chemoradiation therapy. It still, however, remains unclear who is
      likely to achieve a pathological complete response, which unequivocally portends
      a very favorable overall prognosis. Evolution of modern imaging techniques has
      paved the way for potential prediction of treatment response based on baseline,
      on-treatment, early post-treatment and subsequent follow-up imaging alone.
      Independent of tumor grade and stage, tumor marker levels, tumor size, radiation
      dose and fractionation, chemotherapy regimen, and extent/type of surgery, imaging
      biomarkers like circumferential resection margin (CRM), extramural venous space
      invasion (EMVI), imaging-based tumor regression grade, perfusion/diffusion-based
      functional imaging parameters, and imaging-based metabolic response have the
      ability to predict the likelihood of local recurrence and/or distant metastases.
      Textural features of images can add a further dimension to the predictive power
      of imaging. Finally, integration of genomic data with imaging biomarkers can
      potentially discern molecular mechanisms associated with distinct radiographic
      attributes of tumors. In this review, we evaluate and summarize the evidence to
      date of each imaging modality as a biomarker and its contribution to personalized
      decision making in rectal cancer.

PMID- 30097235
TI  - Immune-checkpoint inhibitors in non-small cell lung cancer: A tool to improve
      patients' selection.
AB  - The identification of reliable predictive biomarkers of efficacy or resistance to
      immune-oncology (I-O) agents is a major issue for translational research and
      clinical practice. However, along with PDL1 and molecular features other
      clinical, radiological and laboratory factors can be considered for the selection
      of those patients who would not be the best candidate for immune-checkpoint
      inhibitors (ICPIs). We examined these factors, emerging from the results of
      currently available studies in non-small cell lung cancer (NSCLC), aiming to
      provide a useful and manageable tool which can help Oncologists in their everyday
      clinical practice. A thorough patient evaluation and close clinical monitoring,
      due to limited, early or inconclusive currently available data, should be
      deserved for patients with a pre-existing symptomatic chronic obstructive
      pulmonary disease, age >75 years, Eastern Cooperative Oncology Group (ECOG)
      performance status (PS) >= 1, a time to progression (TTP) < three months and
      progressive disease (PD) as the best response to the previous treatment,
      hepatitis or HIV-infections, high neutrophil to lymphocyte ratio (NLR), or on
      treatment with high-dose steroids, when the use of ICPIs is considered. Limited
      data are available to consider that ICPIs are safe in patients with interstitial
      lung disease, bronchiolitis obliterans organizing pneumonia and autommune
      diseases. Early evidence on steroids, vaccinations and antibiotics suggest their
      possible interaction with ICPIs and need to be more investigated in clinical
      trials. Oncogene-addicted NSCLC harboring EGFR-mutations and low tumor
      infiltrating T-lymphocytes (TILs) seems not to gain benefit from I-O.

PMID- 30097237
TI  - Clinical and circulating biomarkers of survival and recurrence after
      radiofrequency ablation in patients with hepatocellular carcinoma.
AB  - Radiofrequency ablation (RFA) is an effective local treatment for curative intent
      in patients with cirrhosis of the liver and hepatocellular carcinoma (HCC) with
      diameter <3 cm. Several meta-analyses have shown that RFA and surgical resection
      are comparable in terms of their impact on overall survival. The only clinical
      data available on markers that are predictive of recurrence and survival after
      RFA treatment are based on retrospective observational studies. Prospective
      randomized trials are thus needed to further research in this area. In the
      present review we analyzed a number of clinical factors that are considered to
      predict recurrence or survival in HCC patients treated with RFA. We also
      discussed in detail the circulating biomarkers investigated to date, together
      with their potential to predict prognosis and recurrence after RFA therapy.
      Overall survival rates of patients with HCC are significantly affected by liver
      function, defined as Child-Pugh class, high baseline serum alpha-fetoprotein
      levels, and the presence of portosystemic collaterals. However, the development
      of local tumor progression does not significantly affect overall survival. This
      result is achieved by the effective therapies in patients who relapse after
      treatment with RFA. For this reason there is an urgent need to identify new
      circulating biomarkers.

PMID- 30097236
TI  - Immune check-point in cervical cancer.
AB  - Despite different treatment strategies, locally advanced cervical cancer (CC)
      persists as one of the most incurable cancers among women worldwide. In fact,
      this setting of patients are at high risk of persistent and recurrent disease. In
      recent years, researches have investigated immune check-point inhibitors in hopes
      of determining improved response to therapy with prolongation of survival. We
      reviewed the published literature and conference proceedings and presented
      pivotal trials supporting immune check-point inhibitors use in the treatment of
      CC.

PMID- 30097238
TI  - Clinical implication of changes in body composition and weight in patients with
      early-stage and metastatic breast cancer.
AB  - Breast cancer represents the most frequent cancer among women in Western
      countries. Although physicians and patients have witnessed a significant
      evolution in both treatment strategies and personalized medicine (the
      identification of featured patients' subsets such as HER2-driven disease), the
      identification of additional prognostic clinical predictors referring to
      patients' dietary habits represents a research area aiming to further improve the
      overall management of this disease. In this regard, body composition (i.e. the
      relative proportion of fat and muscles) and its changes have recently generated
      growing interest. A large body of evidence supports the relationship between
      overweight or weight gain and poor outcome in patients with early-stage breast
      cancer during adjuvant, and more recently, also neoadjuvant therapy.
      Nevertheless, available data on post-diagnosis weight variations and mortality
      report controversial results. Indeed, the limited data produced in the metastatic
      setting do not indicate an impact of body size on the outcome of these patients.
      With these perspectives, this review aims to elucidate the complex association
      between weight, body composition and breast cancer outcome, across the different
      settings of such disease. The more recent and important findings are highlighted,
      emphasizing the potential role of body composition assessment to predict
      individualize chemotherapy dosing, toxicity and efficacy, in order to improve the
      overall health status and prognosis of such still to date growing patients'
      population.

PMID- 30097239
TI  - Do SABR-related toxicities for lung cancer depend on treatment delivery?
AB  - Stereotactic ablative radiation therapy for lung cancer is an advanced technique
      where tumours are ablated with hypofractionated radiation doses, with a high
      degree of accuracy. The aim of this paper is to review the available literature
      and to discuss the SABR-induced toxicities for lung malignancies as a function of
      radiation delivery technique. A Medline search was conducted to identify the
      appropriate literature to fulfil the aim of this review and data from all
      applicable papers were collated and analysed. The most common techniques of SABR
      delivery employ linear accelerators, CyberKnife robotic radiosurgery system,
      TomoTherapy and the Novalis beam surgery system. Linear accelerator-based
      treatments give rise to a variety of toxicities that are strongly dependent on
      both patient-related factors and planning/dosimetry-related factors. The limited
      number of studies using CyberKnife reported low grade toxicities. Grade three
      toxicities mainly include fatigue and chest pain, usually in less than 10% of
      patients. All treatment techniques presented show efficiency in SABR delivery
      with various toxicities which, at this stage, cannot render one technique better
      than the other. For more conclusive results, well-designed phase three randomised
      clinical trials are required with better patient selection criteria, including
      dose and fractionation, treatment machine and technique, along with the
      consistent selection of a common toxicity grading criterion.

PMID- 30097240
TI  - A quick scoping review of efficacy, safety, economic, and health-related quality
      of-life outcomes of short- and long-acting erythropoiesis-stimulating agents in
      the treatment of chemotherapy-induced anemia and chronic kidney disease anemia.
AB  - Erythropoiesis-stimulating agents (ESAs) are man-made forms of erythropoietin
      used in the treatment of anemia. This quick-scoping review of systematic
      literature reviews (SLRs) was conducted to define the clinical, economic, and
      health-related quality of life (HRQoL) outcomes for short-acting and long-acting
      ESAs in patients with chronic kidney disease-induced anemia (CKD-IA) and patients
      with chemotherapy-induced anemia (CIA). Embase, Medline, and the Cochrane
      Database of Systematic Reviews were searched from their establishment until
      October 2017. SLRs related to the use of short-acting and long-acting ESAs in the
      treatment of CIA and CKD-IA were included. Forty-eight studies met the inclusion
      criteria. The evidence suggests little difference in efficacy, HRQoL, and safety
      outcomes among ESA types. Cost-effectiveness and market price are likely to
      become determining factors driving the choice of agent. Comparative studies and
      costing models accounting for the utilization of biosimilars are needed to
      establish which ESAs are more cost-effective.

PMID- 30097241
TI  - Ablative stereotactic radiotherapy for oligometastatic colorectal cancer:
      Systematic review.
AB  - BACKGROUND: SBRT is a novel modality in treatment for oligometastatic colorectal
      cancer. We aimed to perform a systematic review of results of SBRT in maintaining
      LC (local control) for CRC liver and lung oligometastases. MATERIALS AND METHODS:
      The review was performed according to PRISMA and PICO guidelines. Database search
      using keywords: stereotactic, colon, colorectal, cancer, sbrt, sabr returned 457
      results. 15 were included in the study. Only cohorts with CRC histology and
      reported LC were included. RESULTS: For liver LC rates ranged from 50% to 100%
      after 1 year and 32% to 91% after 2 years. BED range 40.5-262.5 Gy (Gray). For
      lung LC rates ranged from 62% to 92% after 1 one year and from 53% to 92% after 2
      years. BED range 51.3-262.5 Gy. CONCLUSIONS: SBRT of oligometastatic CRC offers
      high LC with low morbidity and toxicity. It requires more observational studies
      and randomized trials but available data on clinical efficacy is promising,
      however not yet matured.

PMID- 30097246
TI  - Quantitative Measurement of the Improvement Derived From a 10-Mo Progressive
      Exercise Program to Improve Balance and Function in Women at Increased Risk for
      Fragility Fractures.
AB  - INTRODUCTION/BACKGROUND: Osteoporosis is a common disorder and is associated with
      an increased risk of bone fracture. Falls are a proximate cause of a high
      proportion of medical costs and mortality. Improving balance can reduce the risk
      of falls and improve health outcomes, especially for the at-risk population of
      people with osteoporosis and osteopenia. The FrameWorksTM exercise program is a
      formal, standardized, informational and interventional 10-month exercise program.
      The purpose of this study was to quantitatively assess the improvement in
      standing balance, functional reach, and overall confidence in balance after
      participating in the 10-month program. METHODOLOGY: This study is a prospectively
      designed study with a pre and post study measurement of balance metrics. Sixty
      two female participants, 45 years of age or older and at increased risk for
      fragility fractures, completed the 10-month program as well the pre and post
      program testing. Confidence was measured with the Activities-specific Balance
      Confidence Scale, a self-reported survey. Balance was measured digitally by means
      of testing with a NeuroCom(r) Basic Balance Master(r) system. Measurements were
      made of the Limits of Stability (LOS) Test and Modified Clinical Test of Sensory
      Interaction on Balance (mCTSIB). Balance was clinically assessed with the
      Functional Reach Test (FRT). RESULTS: Participation in the 10 months FrameWorksTM
      program resulted in improvement in quantitative measures of balance (Composite
      Sway Velocity, -12%, p < 0.001; End point excursion, 17.1%, p < 0.000001). A
      clinical measure of balance, the Functional Reach Test, improved, (2.9 cm, p <
      0.0001). Participation also resulted in improvement in balance confidence (9.4 %,
      p < 0.00001). A height increase was observed (0.6 cm, p < 0.000001). CONCLUSIONS:
      The 10-month FrameWorksTM program improves balance and confidence in women at
      risk for fragility fractures. By improving balance and confidence, people are
      less likely to fall and therefore sustain fewer fractures and associated
      injuries.

PMID- 30097247
TI  - A cross-sectional analysis of clinical evaluation in 35 individuals with
      mutations of the valosin-containing protein gene.
AB  - Inclusion body myopathy (IBM) associated with Paget disease of the bone and
      frontotemporal dementia or IBMPFD is an autosomal dominant degenerative disorder
      caused by mutations in the valosin-containing protein (VCP) gene. We aim to
      establish a detailed clinical phenotype of VCP disease amongst 35 (28 affected
      individuals, 7 presymptomatic gene carriers) individuals versus 14 unaffected
      first-degree relatives in 14 families to establish useful biomarkers for IBMPFD
      and identify the most meaningful tests for monitoring disease progression in
      future clinical trials. Comprehensive studies included the Inclusion Body
      Myositis Functional Rating Scale (IBMFRS) and fatigue severity scale
      questionairres, strength measurements using the Manual Muscle Test with Medical
      Research Council (MRC) scales, hand-held dynamometry using the microFET and
      Biodex dynamometers, 6 minute walk test (6MWT), and pulmonary function studies.
      Strong correlation was observed between the IBMFRS and measurements of muscle
      strength with dynamometry and the other functional tests, indicating that it may
      be utilized in long-term follow-up assessments due to its relative simplicity.
      This cross-section study represents the most comprehensive evaluation of
      individuals with VCP disease to date and provides a useful guide for evaluating
      and possible monitoring of muscle weakness and pulmonary function progression in
      this unique cohort of individuals.

PMID- 30097248
TI  - Respiratory insight to congenital muscular dystrophies and congenital myopathies
      and its relation to clinical trial.
AB  - Congenital muscular dystrophies and congenital myopathies represent a
      heterogeneous group of disorders of the muscle characterized by an early onset of
      hypotonia and muscle weakness and consequently, a high respiratory morbidity and
      mortality. The diagnosis and characterization of the weakness of the respiratory
      muscles is crucial for clinical management of patients and the evaluation of
      innovative therapies. Routine respiratory evaluation is based on noninvasive
      volitional tests, such as the measurement of lung volumes, spirometry, and
      maximal static pressures, which may be difficult or impossible to obtain in young
      children. Tests using natural maneuvers such as a sniff, a cough or a whistle,
      are easier to perform and may be more informative in young children. The
      combination of multiple tests of respiratory muscle function is essential and
      both increases diagnosis accuracy and the strength of the data in case of
      clinical trials assessing new therapies for these diseases.

PMID- 30097249
TI  - The dynamic relationship between insight and suicidal behavior in first episode
      psychosis patients over 3-year follow-up.
AB  - Studies have established the high risk of suicide in first episode psychosis
      (FEP). Between 15% and 26% of FEP patients attempt suicide at least once before
      their first contact with psychiatric services and 2-5% die from suicide. Also,
      many patients with schizophrenia spectrum disorders lack insight into having a
      mental disorder. However, the relationship between insight changes and suicidal
      behavior in FEP remains poorly understood. In the present study information about
      suicidal behavior over a 3 years period was available on a cohort of 397 FEP
      patients, of whom 270 were assessed in the three dimensions of insight (into
      mental illness, the need for treatment, and the social consequences) at baseline,
      1 and 3 years after treatment initiation. Survival analyses examined time to
      suicidal behavior in relation to (i) insight at baseline, (ii) the closest
      insight measure to the suicide attempt, and (iii) changes in insight during the
      follow-up. No associations were found between baseline insight dimensions and
      time to suicidal behavior. However, poor insight at the evaluation closest to the
      suicide attempt was associated with an increased risk of suicide. Stability of
      insight did not affect the risk of suicidal behavior, while changes in either
      direction were linked with an increased risk of suicidal behavior, particularly
      worsening insight. Insight in psychosis is a dynamic concept and we demonstrated
      the relationship between insight and suicide risk to be equally dynamic. Poor
      insight seems to increase the risk, especially when insight levels change.
      Repeated insight assessment to detect change from early psychosis may play a role
      in suicide prevention.

PMID- 30097250
TI  - Does deep inspiration breath-hold prolong life? Individual risk estimates of
      ischaemic heart disease after breast cancer radiotherapy.
AB  - PURPOSE: Aim of the current comparative modelling study was to estimate the
      individual radiation-induced risk for death of ischaemic heart disease (IHD)
      under free breathing (FB) and deep inspiration breath-hold (DIBH) in a real-world
      population. MATERIALS AND METHODS: Eighty-nine patients with left-sided early
      breast cancer were enrolled in the prospective SAVE-HEART study. For each patient
      three-dimensional conformal treatment plans were created in FB and DIBH and
      corresponding radiation-induced risks of IHD mortality were estimated based on
      expected survival, individual IHD risk factors and the relative radiation-induced
      risk. RESULTS: With the use of DIBH, mean heart doses were reduced by 35%
      (interquartile range: 23-46%) as compared to FB. Mean expected years of life lost
      (YLL) due to radiation-induced IHD mortality were 0.11 years in FB, and 0.07
      years in DIBH. YLL were remarkably independent of age at treatment in patients
      with a favourable tumour prognosis. DIBH led to more pronounced reductions in YLL
      in patients with high baseline risk (0.08 years for upper vs 0.02 years for lower
      quartile), with favourable tumour prognosis (0.05 years for patients without vs
      0.02 years for those with lymph-node involvement), and in patients with high mean
      heart doses in FB (0.09 years for doses >3 Gy vs 0.02 years for doses <1.5 Gy).
      CONCLUSION: Ideally, the DIBH technique should be offered to all patients with
      left-sided breast cancer. However, highest benefits are expected for patients
      with a favourable tumour prognosis, high mean heart dose or high baseline IHD
      risk, independent of their age.

PMID- 30097251
TI  - A machine learning-based prediction model of H3K27M mutations in brainstem
      gliomas using conventional MRI and clinical features.
AB  - BACKGROUND: H3K27M is the most frequent mutation in brainstem gliomas (BSGs), and
      it has great significance in the differential diagnosis, prognostic prediction
      and treatment strategy selection of BSGs. There has been a lack of reliable
      noninvasive methods capable of accurately predicting H3K27M mutations in BSGs.
      METHODS: A total of 151 patients with newly diagnosed BSGs were included in this
      retrospective study. The H3K27M mutation status was obtained by whole-exome,
      whole-genome or Sanger's sequencing. A total of 1697 features, including 6
      clinical parameters and 1691 imaging features, were extracted from pre- and post
      contrast T1-weighted and T2-weighted images. Using a random forest algorithm, 36
      selected MR image features were integrated with 3 selected clinical features to
      generate a model that was predictive of H3K27M mutations. Additionally, a
      simplified prediction model comprising the Karnofsky Performance Status (KPS) at
      diagnosis, symptom duration at diagnosis and edge sharpness on T2 was established
      for practical clinical utility using the least squares estimation method.
      RESULTS: H3K27M mutation was an independent prognostic factor that conferred a
      worse prognosis (p = 0.01, hazard ratio = 3.0, 95% confidence interval [CI], 1.57
      5.74). The machine learning-based model achieved an accuracy of 84.44% (area
      under the curve [AUC] = 0.8298) in the test cohort. The simplified model achieved
      an AUC of 0.7839 in the test cohort. CONCLUSIONS: Using conventional MRI and
      clinical features, we established a machine learning-based model with high
      accuracy and a simplified model with improved clinical utility to predict H3K27M
      mutations in BSGs.

PMID- 30097252
TI  - Circulating cell-free DNA: A potential biomarker to differentiate inflammation
      and infection during radiochemotherapy.
AB  - BACKGROUND AND PURPOSE: Radiochemotherapy is a standard treatment option for
      patients with head and neck cancer (HNSCC). During radiation, local toxicities
      are common and need to be differentiated from infections. As levels of
      circulating cell-free DNA (cfDNA) are known to be elevated during infections,
      cfDNA might complement clinical parameters. The aim of the study was to
      investigate the dynamics of cfDNA during radiochemotherapy. MATERIAL AND METHODS:
      In total, 78 blood samples of 20 patients with HNSCC were analysed in this
      prospective biomarker study. Blood samples were taken before and during
      treatment. CfDNA levels were quantified fluorometrically and results were
      compared to laboratory and clinical parameters. RESULTS: Elevated cfDNA levels
      were associated with the pre-treatment volumes of lymph node metastases (p =
      0.0002), gastrostomy tube placement (20.23 ng/ml vs. 9.04 ng/ml (median), p =
      0.025), the application of antibiotics (16.47 ng/ml vs. 9.04 ng/ml, p = 0.006)
      and manifest infections (16.81 ng/ml vs. 9.04 ng/ml, p = 0.010). Furthermore, a
      significant difference between moderate inflammation (radiation-induced toxicity
      RTOG grade 2-3) and manifest infections could be observed (8.97 ng/ml vs. 16.81
      ng/ml, p = 0.014), allowing for a more pronounced differentiation than by CRP
      levels (p = 0.119). There might be an association between the application of G
      CSF and elevated cfDNA levels. CONCLUSION: CfDNA levels are correlated with
      infections during radiochemotherapy and could represent an informative
      complemental biomarker to drive therapeutic decision-making. Estimated levels of
      circulating cell-free tumour DNA (ctDNA) in plasma should be interpreted
      cautiously when monitoring tumour outcome by next-generation-sequencing, as
      confounders like infections or drug application might influence the fraction of
      ctDNA in total cfDNA.

PMID- 30097253
TI  - Mast cell activation syndrome: High frequency of skin manifestations and
      anaphylactic shock.

PMID- 30097254
TI  - Spontaneous Regression of a Low-Grade Renal Cell Carcinoma With Oncocytic
      Features After Renal Mass Biopsy.

PMID- 30097256
TI  - Enhanced treatment of lung cancer by metronomic therapy with oral pemetrexed.

PMID- 30097255
TI  - Factors Associated With Posthospital Nursing Facility Discharge for Patients With
      Impaired Decision Making.

PMID- 30097257
TI  - Physical insights of ultrasound-assisted ethanol production from composite
      feedstock of invasive weeds.
AB  - Invasive weeds ubiquitously found in terrestrial and aquatic ecosystems form
      potential feedstock for lignocellulosic ethanol production. The present study has
      reported a bioprocess for production of ethanol using mixed feedstock of 8
      invasive weeds found in India. The feedstock was subjected to pretreatment
      comprising dilute acid hydrolysis (for hydrolysis of hemicellulosic fraction),
      alkaline delignification and enzymatic hydrolysis of cellulosic fraction. Pentose
      rich and hexose-rich hydrolyzates obtained from pretreatment were fermented
      separately using microbial cultures of S. cerevisiae and C. shehatae.
      Fermentation mixture was sonicated at 35 kHz at 10% duty cycle. The time profiles
      of total reducing sugars, ethanol and biomass was fitted to a kinetic model using
      Genetic Algorithm. Sonication boosted the kinetics of fermentation 2-fold. The
      net bioethanol yield of the process was ~220 g/kg raw biomass (with contributions
      of 86.8 and 133 g/kg raw biomass from pentose and hexose fermentations,
      respectively). Comparative evaluation of parameters of kinetic model under
      control and test conditions revealed several beneficial influences of sonication
      on both pentose and hexose fermentation systems such as faster transport of
      nutrients, substrate and products across cell membrane, rise in Monod saturation
      constant for substrate with concurrent reduction in substrate inhibition, and
      reduction of energy requirements for cell maintenance. Flow cytometry analysis of
      native and ultrasound-treated cells revealed no adverse influence of sonication
      on cell viability.

PMID- 30097258
TI  - Sono hydrodistillation for isolation of citronella oil: A symbiotic effect of
      sonication and hydrodistillation towards energy efficiency and environment
      friendliness.
AB  - Environmental benign approach for extraction of essential oil was made. An
      essential oil rich in citronellol, linalool and citronellal was extracted from
      the leaves of Cymbopogon winterianus using a clean hybrid extraction technique,
      sono hydrodistillation. Sono hydrodistillation combines ultrasonic waves along
      with conventional hydrodistillation process to have symbiotic outcomes in terms
      of process improvement. Significant process parameters such as size of the plant
      material, extraction time, power, ultrasound amplitude, pulse interval and solid
      loading were investigated independently to study the effect on yield of oil and
      composition of oil. The water residue remained after extraction of volatile oil
      was analyzed using Folin-Ciocalteu method to determine the total phenolic content
      (TPC) which would help in assessing the residue as a useful by-product.
      Substantial reduction in time was observed with the inclusion of ultrasound
      compared to conventional hydrodistillation. Further, to optimize the extraction
      conditions, observe interactive effects of various parameters and develop
      mathematical model, response surface methodology was employed. The maximum yield
      of oil was found to be 4.118% (w/w) at 21 min extraction time, 5 g solid loading,
      250 mL water volume, 500 W heating mantle power, 70% ultrasonic amplitude and
      10:50 pulse interval. Total phenolic content was 13.84 mg GAE/g DM. The
      citronella oil was found to be composed of 27.47% of linalool, 11.52% of
      citronellal, 34.25% citronellol and 11.15% of elemol. Extraction time, solid
      loading and pulse interval had the significant influence on the yield of oil and
      total phenolic contents. Microscopic analysis has assisted in envisaging the
      probable mechanism indicating the role of sonication for rapid extraction. This
      novel technique was compared with the conventional hydrodistillation to ascertain
      the impact towards process intensification. Sono hydrodistillation was found to
      be a greener and cleaner process as energy consumption has been reduced by 40%
      while carbon footprint has shrunken by 47%.

PMID- 30097259
TI  - Early prediction of sepsis-induced acute kidney injury.

PMID- 30097260
TI  - Intraventricular CNS treatment with Colistin-Tigecycline combination: A case
      series.
AB  - "Healthcare-associated ventriculitis and meningitis" is a potentially devastating
      illness following neurosurgical procedures. Multidrug resistant (MDR) and
      extensively drug resistant (XDR) organisms such as Acinetobacter baumannii and
      Klebsiella pneumoniae have increasingly been isolated in ventriculitis and
      meningitis episodes. The treatment of these infections can be challenging, as the
      antimicrobial options are restricted. Regarding Central Nervous System (CNS)
      infections the transfer of the antibiotics to the Cerebrospinal Fluid (CSF) is
      often low which results in decreased drug levels at the infection site. The
      intraventricular (IVT) administration of antibiotics can be used as an adjunct to
      the intravenous (IV) treatment of Gram-negative MDR ventriculitis and meningitis,
      yet pertinent data is scarce. We present the successful management of three cases
      of healthcare-associated ventriculitis and meningitis due to XDR species with the
      combined intraventricular administration of colistin and off-label tigecycline,
      after the initial regimen of colistin given alone through both IVT and IV routes
      had failed.

PMID- 30097261
TI  - Systematic review: Features, diagnosis, management and prognosis of hepatic
      hematoma, a rare complication of ERCP.
AB  - BACKGROUND: Hepatic hematoma (HH) is a rare but severe adverse event following
      endoscopic retrograde cholangiopancreatography (ERCP). AIMS: To perform a
      systematic literature review and describe two additional cases, one of which
      presenting multiple subcapsular/intrahepatic hematomas after ERCP. METHODS: The
      literature review was performed in PubMed/MEDLINE, EMBASE, and SCOPUS to identify
      all cases reporting on HH after ERCP. RESULTS: A total of 48 cases (females 63%,
      mean age 58.2 +/- 20.6 years) were included. The mean symptoms onset time was
      46.8 h after ERCP, and the most common symptoms were abdominal pain (91.7%),
      anaemia (43.8%), hypotension (29.2%) and fever (20.8%). All cases were diagnosed
      by computed tomography (CT). HH was found mostly in the right hepatic lobe
      (95.1%) and the mean size was 116 * 93 mm. A conservative management was adopted
      in 38.3% of cases, while percutaneous drainage, embolization and surgery were
      needed in 31.9%, 14.9% and 25%. Mortality rate was about 9%. Anaemia (OR 6.9; p =
      0.02) and surgery (OR 10.5; p < 0.01) were the only independent factors for
      unfavorable outcome (death), while abdominal pain (OR 0.1; p = 0.03) and
      antibiotics administration (OR 0.06; p < 0.001) were associated with better
      outcome. CONCLUSIONS: HH is a rare but severe complication following ERCP which
      needs a multidisciplinary approach. Antibiotics administration is the only
      treatment able to reduce the risk of death.

PMID- 30097262
TI  - Bats, Bat Flies, and Fungi: A Case of Hyperparasitism.
AB  - Bats are parasitized by numerous lineages of arthropods, of which bat flies
      (Diptera, Nycteribiidae and Streblidae) are the most conspicuous. Bat flies
      themselves can be parasitized by Laboulbeniales, fungal biotrophs of arthropods.
      This is known as hyperparasitism, a severely understudied phenomenon. Three
      genera of Laboulbeniales occur on bat flies: Arthrorhynchus on Nycteribiidae,
      Gloeandromyces and Nycteromyces on Streblidae. In this review we introduce the
      parasitic partners in this tripartite system and discuss their diversity,
      ecology, and specificity patterns, alongside some important life history traits.
      Furthermore, we cover recent advances in the study of the associations between
      bat flies and Laboulbeniales, which were neglected for decades. Among the most
      immediate needs for further studies are detailed tripartite field surveys. The
      vermin only teaze and pinch Their foes superior by an inch So, naturalists
      observe, a flea Has smaller fleas that on him prey; And these have smaller still
      to bite 'em, And so proceed ad infinitum. Jonathan Swift (On Poetry: A Rhapsody,
      1733).

PMID- 30097263
TI  - Effect of photodynamic therapy on the mechanical properties and bond strength of
      glass-fiber posts to endodontically treated intraradicular dentin.
AB  - STATEMENT OF PROBLEM: The use of photosensitizers in photodynamic therapy
      promotes intraradicular microbial reduction during nonsurgical endodontic
      therapy. However, studies are lacking on the consequences of the application of
      these agents on the mechanical properties of intraradicular dentin and on the
      bond strength of glass-fiber posts. PURPOSE: The purpose of this in vitro study
      was to evaluate the influence of photodynamic therapy on the bond strength of
      glass-fiber posts using a push-out test and, additionally, to measure the Martens
      hardness (MH) and elastic indentation modulus (Eit) of intraradicular dentin when
      different photosensitizers are used. MATERIAL AND METHODS: Eighty bovine teeth
      were used to simulate experimental endodontic treatments. Biomechanical
      instrumentation was performed for all root canals, and the teeth were distributed
      into 5 groups: control-deionized water; methylene blue 50 mg/L + red laser;
      methylene blue 100 mg/L + red laser; curcumin 500 mg/L + blue LED; and curcumin
      1000 mg/L + blue LED. The MH and Eit of intraradicular dentin were measured using
      an ultramicrohardness tester under a load of 3 mN (n=8). The push-out bond
      strength of glass-fiber posts to dentin was measured using a universal testing
      machine (n=8). Mechanical properties and bond strength data were subjected to the
      Kruskal-Wallis test, ANOVA, and Fisher least significant difference test
      (alpha=.05). Images of representative specimens were obtained using a scanning
      electron microscope. RESULTS: The MH, Eit, and bond strength of intraradicular
      dentin were influenced by the photosensitizer used. In general, curcumin promoted
      lower mechanical properties values but higher bond strength values. CONCLUSIONS:
      Photosensitizers influenced the mechanical properties of intraradicular dentin
      and the bond strength of glass-fiber posts, and methylene blue at 50 mg/L had no
      marked effect on the mechanical properties of the dentin or the bond strength
      values.

PMID- 30097264
TI  - Wear resistance and abrasiveness of CAD-CAM monolithic materials.
AB  - STATEMENT OF PROBLEM: Computer-aided design and computer-aided manufacturing (CAD
      CAM) restorations are in contact with the antagonist tooth, either a natural
      tooth or a restoration. Therefore, clinicians should be aware of the wear
      resistance of CAD-CAM materials and the wear behavior of the antagonist. PURPOSE:
      The purpose of this in vitro study was to evaluate the wear resistance and
      abrasiveness of CAD-CAM materials. MATERIAL AND METHODS: In a 2-body wear test,
      the materials IPS e.max CAD (Ivoclar Vivadent AG), Vita Suprinity (Vita
      Zahnfabrik), Lava Ultimate (3M ESPE), Vita Enamic (Vita Zahnfabrik), and Lava
      Plus (3M ESPE) acted as abraders and, together with bovine enamel, also as
      antagonists. Each antagonist wheel ran against each abrader wheel for 200000
      cycles, with a spring force of 15 N, and at a rotational speed of 1 Hz in
      distilled water. The wear rate was determined with a surface profilometer. The
      surfaces were observed with scanning electron microscopy, and their hardness,
      coefficient of friction, and roughness were evaluated. RESULTS: Lava Plus and IPS
      e.max CAD exhibited the highest potential for wear of Lava Ultimate. These 2
      materials, together with Vita Suprinity, provided the highest wear of enamel and
      Vita Enamic. Vita Suprinity and IPS e.max CAD had higher wear than Lava Plus, and
      the inverse was also true. Vita Enamic and Lava Ultimate were among the materials
      that caused the lowest wear of enamel and all other evaluated materials. Scanning
      electron microscopy images revealed that except for Lava Ultimate, all other
      materials damaged enamel, in which Vita Suprinity and IPS e.max CAD were more
      aggressive when sliding against the materials. Lava Plus had the greatest
      hardness, followed by Vita Suprinity and IPS e.max CAD, Vita Enamic, and then
      Lava Ultimate. The coefficient of friction varied from 0.42 to 0.53. The Vita
      Enamic and Lava Ultimate showed the highest surface roughness. CONCLUSIONS: The
      nanofilled composite resin and polymer-infiltrated ceramic were more antagonist
      friendly (whether enamel or CAD-CAM material) than glass-ceramics and zirconia.
      Care should be taken when selecting the material that will contact mainly with
      glass-ceramics. Hardness should also be considered when selecting a material.

PMID- 30097265
TI  - Effects of heat treatment on metal-ceramic combination of selective-laser-melted
      cobalt-chromium alloy.
AB  - STATEMENT OF PROBLEM: Components fabricated by selective laser melting (SLM)
      deform because of residual stress, but heat treatment allows the release of that
      stress and avoids deformation. Although dental cobalt-chromium (Co-Cr) alloy has
      been specifically designed for SLM, the effects of heat treatment on the metal
      ceramic combination of SLM Co-Cr restorations require investigation. PURPOSE: The
      purpose of this in vitro study was to evaluate the effects of heat treatment on
      the metal-ceramic combination of SLM Co-Cr alloy. MATERIAL AND METHODS: Following
      ISO 9693:2012, Co-Cr metal strips (Solibond C Plus cast alloy and SLM powders;
      YETI Dental) were fabricated with a dimension of 25*3*0.5 mm by casting and SLM.
      The SLM specimens were divided into 3 subgroups (n=15 for each subgroup). Two
      subgroups were subjected to heat treatment at 880 degrees C (SLM-880) and 1100
      degrees C (SLM-1100). The third subgroup was not subjected to heat treatment and
      served as a control (As-SLM). Cast specimens (n=15) also acted as a control. A
      porcelain layer with a thickness of 1.1 mm was fired to the central area (3*8 mm)
      of each specimen. The 3-point bend test was used to evaluate the metal-ceramic
      bond strength (taub). The fractured metal surfaces were examined by the naked
      eye, using a digital camera, and also using a scanning electron microscope. The
      area fraction of adherence porcelain (AFAP) was determined by measuring the
      atomic percentage of silicon using energy-dispersive x-ray spectroscopy (EDS).
      One-way ANOVA and the Kruskal-Wallis test, followed by the Mann-Whitney test
      (alpha=.05), were used for statistical analysis. RESULTS: The 1-way ANOVA found
      no significant difference in the bond strength among the 4 groups. The EDS
      analysis indicated that specimens in the groups receiving heat treatment (SLM-880
      and SLM-1100) showed higher AFAP values than those in the As-SLM group (P<.05).
      The SLM-880 also showed significantly higher AFAP values than the SLM-1100.
      Compared with the cast group, significant differences in AFAP values were also
      observed, and the specimens in the order of highest to lowest AFAP values were
      SLM-880>cast>As-SLM; no significant difference was found between the SLM-1100 and
      cast groups. CONCLUSIONS: Heat treatment at 880 degrees C and 1100 degrees C did
      not affect the metal-ceramic bond strength of Co-Cr alloy made by SLM but did
      improve the porcelain adherence. SLM-fabricated and heat-treated Co-Cr alloy
      shows comparable or more porcelain adherence than cast specimens.

PMID- 30097266
TI  - The influence of systemic-to-pulmonary arterial shunts and peripheral
      vasculatures in univentricular circulations: Focus on coronary perfusion and
      aortic arch hemodynamics through computational multi-domain modeling.
AB  - Initial palliation for univentricular hearts can be achieved via a systemic-to
      pulmonary shunt (SPS). SPS configurations differ depending on the proximal
      anastomosis location, which might lead to dissimilar coronary and upper body
      perfusions. Mathematical modeling can be used to explore the local and global
      hemodynamic effects of the SPSs. In literature there are few patient-specific
      models of SPS that specifically address the influence of both the local and
      peripheral vasculature. In this study, multi-domain models of univentricular
      circulations were developed to investigate local hemodynamics and flow
      distribution in the presence of two shunt configurations. We also analyzed the
      relative impact of local and peripheral vascular resistances on coronary
      perfusion and flows through the upper aortic branches. A two-step approach was
      followed. First, two patient-specific models were based on clinical data
      collected from univentricular patients having different shunts and peripheral
      vasculatures. Each model coupled a three-dimensional representation of SPS,
      aortic arch (AA) and pulmonary arteries, with a lumped parameter model (LPM) of
      peripheral vasculature closing the circulatory loop. Then, two additional models
      of hypothetical subjects were created by coupling each customized LPM with the
      other patient's three-dimensional anatomy. Flow rates and pressures predicted by
      the patient-specific models revealed overall agreement with clinical data.
      Differences in the local hemodynamics were seen during diastole between the two
      models. Varying the three-dimensional models, while keeping an identical LPM, led
      to comparable flow distribution through the AA, suggesting that peripheral
      vasculatures have a dominant effect on local hemodynamics with respect to the
      shunt configuration.

PMID- 30097267
TI  - Altered joint kinetic strategies of healthy older adults and individuals with
      Parkinson's disease to walk at faster speeds.
AB  - Individuals with Parkinson's disease (PD) exhibit poorer walking performance
      compared to healthy, age-matched adults. Lower extremity joint kinetics may
      provide insight into this performance deficit but are currently lacking in the PD
      literature, especially across multiple speeds. The primary purpose of this study
      was to compare joint kinetics between individuals with PD and healthy older
      adults at both comfortable and maximal walking speeds. Secondarily, we quantified
      relationships between joint kinetics and walking speeds within each group.
      Biomechanical gait analyses were conducted for 13 individuals with PD and 12 age
      matched controls during comfortable (CWS) and maximal (MWS) speed walking.
      Relative contributions to total positive work from the hip, knee, and ankle were
      compared across groups and speeds. Within each group, relationships between
      relative joint work and CWS and MWS were also quantified. Significant group by
      speed interactions indicated that healthy older adults increased hip and
      decreased ankle relative work at MWS compared to CWS whereas relative work at all
      joints in PD group remained stable across speeds. In the older group, positive
      relationships were observed between relative hip work and MWS. In the PD group,
      negative relationships were observed between relative hip work and CWS and MWS.
      Healthy older adults disproportionately increased mechanical contributions from
      the hip at MWS compared to CWS. Individuals with PD did not exhibit similar
      disproportionate scaling of joint kinetics across speed conditions. Inability to
      appropriately scale joint kinetics in PD may represent an inflexible
      neuromuscular system in PD, which may limit walking performance in this
      population.

PMID- 30097268
TI  - Wheelchair propulsion: Force orientation and amplitude prediction with Recurrent
      Neural Network.
AB  - The aim of this study was to use Recurrent Neural Network (RNN) to predict the
      orientation and amplitude of the applied force during the push phase of manual
      wheelchair propulsion. Trunk and the right-upper limb kinematics data were
      assessed with an optoeletronic device (Qualisys) and the force applied on the
      handrim was recorded with an instrumented wheel (SMARTWheel(r)). Data
      acquisitions were performed at 60/80/10/120/140% of the freely chosen frequency
      at submaximal and maximal conditions. The final database consisted of d = 5708
      push phases. The input data were the trunk and right upper-limb kinematics (joint
      angle, angular velocity and acceleration) and anthropometric data (height,
      weight, segment length) and the output data were the applied forces orientation
      and amplitude. A ratio of 70/15/15 was used to train, validate and test the RNN
      (dtrain = 3996, dvalidation = 856 and dtest = 856). The angle and amplitude
      errors between the measured and predicted force was assessed from dtest. Results
      showed that for most of the push phase (~70%), the force direction prediction
      errors were less than 12 degrees . The mean absolute amplitude errors were less
      than 8 N and the mean absolute amplitude percentage errors were less than 20% for
      most of the push phase (~80%).

PMID- 30097269
TI  - Maize similar to RCD1 gene induced by salt enhances Arabidopsis thaliana abiotic
      stress resistance.
AB  - Plant SRO (SIMILAR TO RCD-ONE) proteins play important roles in regulating
      oxidation and metal ion metabolism. Numbers of SRO proteins have been functional
      identified in Arabidopsis and rice, but little is known in maize. In this study,
      we identified a salt induced SRO gene, ZmSRO1b, from maize and analyzed its
      characteristics. ZmSRO1b expressed mainly in leaf tissues. The ZmSRO1b is encoded
      by 595 amino acid residues and shared conserved protein models with AtRCD1 and
      AtSRO1 from Arabidopsis. Promoter-elements analysis showed ZmSRO1b promoter
      harbored salt and metal stress responsive elements, DRE, GT-like and MRE. Further
      promoter inductive analysis by GUS staining and quantification confirmed that
      ZmSRO1b promoter was induced by salt and cadmium (Cd). Methylviologen (MV)
      simulated oxidative stress showed ZmSRO1b promoter was also induced by MV.
      Overexpression of ZmSRO1b in Arabidopsis plants showed increased resistance to
      salt, Cd and oxidative stress. Our results for the first time experimentally
      validate the function of ZmSRO1b and contribute to the better understanding of
      SRO genes across different plant species.

PMID- 30097270
TI  - Gliadin intake induces oxidative-stress responses in Caenorhabditis elegans.
AB  - Clinical attention to gluten-related disorders, such as celiac disease and
      nonceliac gluten sensitivity, is on the rise. However, identifying the
      pathophysiological mechanisms of gluten-related disorders remains elusive.
      Gliadin, a component of gluten, is known to play a major role in gluten toxicity.
      Caenorhabditis elegans has been widely used as the predominant experimental
      animal model to study toxicity and stress response in biomedical research. We
      investigated the stress response induced by gliadin intake in C. elegans to
      evaluate its toxicity and found brood size, body bending, and pumping rates to be
      significantly altered in response to gliadin. Notably, reactive oxygen species
      (ROS) production and Pgst-4::GFP transgene expression, an indicator of the
      oxidative-stress response, were significantly increased after gliadin intake.
      Reduced pumping rates were most likely caused by gliadin-induced oxidative
      stress, since pumping rates in oxidative stress-sensitive mev-1 mutants were more
      severely reduced than in oxidative stress-resistant daf-2 mutants following
      gliadin intake. Our results indicated that gluten/gliadin intake in C. elegans
      triggered ROS production and induced an oxidative stress response that reduced
      pumping rates and decreased brood size. We suggest C. elegans to be a useful
      model system for studying gluten/gliadin toxicity.

PMID- 30097271
TI  - iRhom2 promotes atherosclerosis through macrophage inflammation and induction of
      oxidative stress.
AB  - Atherosclerosis is a complex chronic inflammatory disease that is characterized
      by the formation of lipid-rich plaques on the inner walls of the arteries.
      Inactive rhomboid protein 2 (iRhom2) was recently determined as a necessary
      regulator for the shedding of tumor necrosis factor-alpha (TNF-alpha) in immune
      cells. In the present study, we aimed to explore the effects of iRhom2 on the
      inflammatory response and oxidative stress induced by low-density lipoprotein (ox
      LDL) in RAW264.7 and THP-1-derived macrophages. The expression levels of iRhom2
      were also investigated in apolipoprotein E knockout (ApoE-/-) mice fed a high-fat
      diet (HFD). iRhom2 was significantly induced by ox-LDL in macrophages, as
      confirmed by Western blotting and RT-qPCR analysis. Furthermore, iRhom2 knockdown
      showed significant suppressive effects on the activation of ox-LDL-induced
      RAW264.7 and THP-1-derived macrophages through reducing TACE and TNFR2
      expressions, and the inactivation of the IkappaBalpha/NF-kappaB signaling
      pathway. A reduction in reactive oxygen species (ROS) generation, malondialdehyde
      (MDA) levels, and nitric oxide (NOX) activity and an increase in glutathione
      peroxidase (GSH-Px) activity were determined in the absence of iRhom2 expression.
      In addition, the NF-E2 related factor-2 (Nrf-2)/heme oxygenase-1 (HO-1) pathway
      was also upregulated in ox-LDL-treated macrophages subjected to iRhom2
      inhibition. Moreover, suppression of iRhom2 expression inactivated PI3K/AKT
      pathway activation, contributing to ROS reduction in ox-LDL-stimulated
      macrophages. iRhom2 was also significantly expressed in ApoE-/- mice fed HFD.
      Finally, we observed increased serum levels of TNF-alpha, TNFR1, and TNFR2 in
      patients with coronary artery atherosclerosis as compared to healthy volunteers.
      In conclusion, our findings suggested that iRhom2 played a key role in the
      pathogenesis of atherosclerosis, and that iRhom2 might be a potential therapeutic
      target against atherosclerosis.

PMID- 30097272
TI  - Impact of an emergency medicine pharmacist on empiric antibiotic prescribing for
      pneumonia and intra-abdominal infections.
AB  - PURPOSE: It is critical to engage ED providers in antimicrobial stewardship
      programs (ASP). Emergency medicine pharmacists (EMPs) play an important role in
      ASP by working with providers to choose empiric antimicrobials. This study aimed
      to determine the impact of an EMP on appropriate empiric antibiotic prescribing
      for community-acquired pneumonia (CAP) and intra-abdominal infections (CA-IAI).
      METHODS: A retrospective cohort study was conducted evaluating adult patients
      admitted with CAP or CA-IAI. The primary outcome of this study was to compare
      guideline-concordant empiric antibiotic prescribing when an EMP was present vs.
      absent. We also aimed to compare the impact of an EMP in an early-ASP vs.
      established-ASP. RESULTS: 320 patients were included in the study (EMP n = 185,
      no-EMP n = 135). Overall empiric antibiotic prescribing was more likely to be
      guideline-concordant when an EMP was present (78% vs. 61%, p = 0.001); this was
      true for both the CAP (95% vs. 79%, p = 0.005) and CA-IAI subgroups (62% vs. 44%,
      p = 0.025). Total guideline-concordant prescribing significantly increased
      between the early-ASP and established-ASP (60% vs. 82.5%, p < 0.001) and was more
      likely when an EMP was present (early-ASP: 68.3% vs. 45.8%, p = 0.005;
      established-ASP: 90.5% vs. 73.7%, p = 0.005). Patients receiving guideline
      concordant antibiotics in the ED continued appropriate therapy upon admission
      82.5% of the time vs. 18.8% if the ED antibiotic was inappropriate (p < 0.001).
      CONCLUSION: The presence of an EMP significantly improved guideline-concordant
      empiric antibiotic prescribing for CAP and CA-IAI in both an early and
      established ASP. Inpatient orders were more likely to be guideline-concordant if
      appropriate therapy was ordered in the ED.

PMID- 30097273
TI  - Reply to the Letter titled "Platelet indices may not be associated with diagnosis
      and prognosis of gastrointestinal bleeding".

PMID- 30097274
TI  - Supraglottic airway device placement by respiratory therapists.
AB  - OBJECTIVE: Respiratory Therapists (RTs) are some of the first staff to arrive at
      in-hospital incidents where cardiopulmonary resuscitation (CPR) is needed, yet at
      some facilities, their ability to intubate is limited by hospital scope of
      practice. During the intubation process, CPR is often interrupted which could
      potentially increase the likelihood of adverse patient outcomes. Training RTs to
      secure the airway using non-intubation methods may reduce or eliminate time for
      CPR interruptions and allow for earlier continuous/uninterrupted chest
      compressions. DESIGN: A pilot study was developed to assess the effectiveness of
      a new policy for RT scope of practice. METHODS: RTs were trained for supraglottic
      airway device placement prior to procedure initiation. After each device
      insertion event, RTs completed a written survey. Time between cardiac arrest and
      device insertion, number of insertion attempts, ease of placement, technical
      specifications of the device, complications, and survival were compiled and
      compared between supraglottic airway device and endotracheal tube (ETT)
      placement. RESULTS: Procedural information from 23 patients who received a
      supraglottic airway device during the trial was compared to retrospective data of
      CPR events requiring intubation from the previous year. Time between initiation
      of cardiac arrest and advanced airway placement decreased significantly (p <
      0.0001) when RTs placed the supraglottic airway device (4.7 min) versus ETT at
      CPR events the previous year (8.6 min). Device-associated complications were
      minimal and patient mortality was the same regardless of device. CONCLUSION: We
      propose that more RTs should be trained to insert supraglottic airway devices
      during inpatient CPR events.

PMID- 30097275
TI  - Assessing the methodological quality of retrospective research protocols.

PMID- 30097276
TI  - Diagnostic accuracy of laboratory and ultrasound findings in patients with a non
      visualized appendix.
AB  - : Ultrasound (US) and laboratory testing are initial diagnostic tests for acute
      appendicitis. A diagnostic dilemma develops when the appendix is not visualized
      on US. OBJECTIVE: To determine if specific US findings and/or laboratory results
      predict acute appendicitis when the appendix is not visualized. METHODS: A
      prospective study was conducted on children (birth-18 yrs) presenting to the
      pediatric emergency department with suspected acute appendicitis who underwent
      right lower quadrant US. Children with previous appendectomy, US at another
      facility, or eloped were excluded. US findings analyzed: inflammatory changes,
      right lower quadrant and lower abdominal fluid, tenderness during US exam and
      lymph nodes. Diagnoses were confirmed via surgical pathology. Results 1252
      subjects were enrolled, 60.8% (762) had appendix visualized and 39.1% (490) did
      not. In children where the appendix was not seen, 6.7% [33] were diagnosed with
      appendicitis. Among patients with a non-visualized appendix, the likelihood of
      appendicitis was significantly greater if: inflammatory changes in the RLQ (OR
      18.0, 95% CI 4.5-72.1), CRP >0.5 mg/dL (OR 2.64, 95% CI 1.0-6.8), or WBC > 10 (OR
      4.36, 95% CI 1.66-11.58). Duration of abdominal pain >3 days was significantly
      less likely associated with appendicitis in this model (OR 0.34, 95% CI 0.003
      0.395). Combined, the absence inflammatory changes, CRP < 0.5 mg/dL, WBC < 10,
      and pain, <=3 days had a NPV of 94.0%. Conclusion When the appendix is not
      visualized on US, predictors for appendicitis include the presence of
      inflammatory changes in the RLQ, an elevated WBC/CRP and abdominal pain <3 days.

PMID- 30097277
TI  - A step forward in radiometabolic treatment of bone metastases with 223Ra.

PMID- 30097279
TI  - Why Doesn't America Like Its Children?

PMID- 30097278
TI  - The efficacy of computerized cognitive drill and practice training for patients
      with a schizophrenia-spectrum disorder: A meta-analysis.
AB  - BACKGROUND: Computerized methods for improving cognitive functioning in
      schizophrenia have gained popularity during the past decades. Therefore, this
      study evaluates the available evidence for the efficacy of computerized cognitive
      drill and practice training for patients with schizophrenia-spectrum disorders.
      METHODS: A systematic search was carried out using PubMed, Embase, Cochrane
      Database of Systematic Reviews, and PsycINFO. A meta-analysis was performed to
      compare cognitive drill and practice training in patients with a schizophrenia
      spectrum disorder with non-cognitively oriented control conditions. The primary
      outcome was cognitive functioning. Secondary outcome measures included psychotic
      symptoms, depressive symptoms, and functional outcomes. Effect sizes (ES) for all
      included studies were calculated as Hedges' g. RESULTS: 24 studies were included
      with 1262 patients in total. Compared to a control condition, patients receiving
      computerized cognitive drill and practice training showed significantly more
      improvement on attention (ES = 0.31, p = 0.001), working memory (ES = 0.38, p <
      0.001), positive symptoms (ES = 0.31, p = 0.003), and depressive symptoms (ES =
      0.37, p = 0.002). Small, marginally significant effect sizes were found for
      processing speed, verbal and visual learning and memory, and verbal fluency.
      However, significant effects on functional outcomes and social cognition were
      absent. DISCUSSION: The current study showed evidence for the efficacy of
      computerized cognitive drill and practice training in patients with schizophrenia
      spectrum disorders. However, the absence of effects on social cognition and
      functional outcomes questions the generalization of treatment effects. Together,
      these results stimulate further development of computerized training programs for
      schizophrenia that not only improve cognitive functioning, but also generalize
      cognitive improvement to functional outcomes.

PMID- 30097280
TI  - [Supportive care for survivors].
AB  - Advances in early detection and treatment have pushed in a few decades the
      management of cancers from a management model of the end of life to the
      management of a chronic disease. This evolution has accelerated the development
      of supportive care in two directions, firstly towards the best possible support
      to the end of life in advanced cancer patients (palliative care) and secondly to
      the limitation of treatment toxicities, the prevention of relapse and the return
      to life as "normal" as possible (care for after cancer). If palliative care now
      has a legitimacy and a solid regulatory base, this is not yet the case of
      supportive care in France. The content and organization differ depending on the
      institution, the choice of clinicians and patient preferences. Social networks
      and media convey messages that blur evidence-based practices. This article aims
      to review the facilitators and obstacles of this perspective.

PMID- 30097281
TI  - The interaction effects of polycyclic aromatic hydrocarbons exposure and TERT-
      CLPTM1L variants on longitudinal telomere length shortening: A prospective cohort
      study.
AB  - Telomere length (TL) is an index of cellular aging and can predict the incidences
      of many age-related diseases. Change of TL might be affected by environmental
      pollution and individual's genetic background. In this cohort study, we aimed to
      evaluate the associations between polycyclic aromatic hydrocarbons (PAHs)
      exposure and longitudinal TL shortening, and investigate whether genetic
      variations in TERT-CLPTM1L can modify these associations. We measured the
      baseline concentrations of twelve urinary PAH metabolites and genotyped six
      variants at TERT-CLPTM1L among 1243 coke-oven workers. The relative leukocyte TL
      was detected in both baseline and follow-up (4 years later) visits. The TL
      shortening were estimated by TL decline and TL ratio. We found that the urinary
      level of 1-hydroxypyrene (1-OHP) had significant dose-response relationships with
      increased TL decline [beta(95%CI) = 0.078(0.023, 0.133), P = 0.005] and TL ratio
      [beta(95%CI) = 0.096(0.037, 0.155), P = 0.002]. Besides, urinary 1
      hydroxynaphthalene (1-OHNa) was marginally dose-related with elevated TL decline
      [beta(95%CI) = 0.053(-0.001, 0.107), P = 0.055] and TL ratio [beta(95%CI) =
      0.057(-0.002, 0.116), P = 0.058]. Analyses of TERT-CLPTM1L variants showed that
      the rs401681 and rs465498 could modify the effect of 1-OHP on increasing TL
      decline (Pinteraction = 0.012 and 0.035, respectively) and TL ratio (Pinteraction
      = 0.014 and 0.067, respectively), which were pronounced among rs401681TT and
      rs465498CC carriers, but not seen among rs401681TC + CC and rs465498CT + TT
      carriers. In conclusion, elevated exposure to PAHs can accelerate the TL
      shortening and this effect can be modified by TERT-CLPTM1L variants. These
      results may add potential evidence for gene-environment interactions on dynamic
      changes of telomere length. Further studies are warranted to validate these
      findings and uncover the underlying mechanisms.

PMID- 30097282
TI  - Endoplasmic reticulum stress mediates 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one
      (DCOIT)-induced toxicity and liver lipid metabolism changes in Nile tilapia
      (Oreochromis niloticus).
AB  - DCOIT (4,5-dichloro-2-n-octyl-4-isothiazolin-3-one) is the main active ingredient
      in an emerging water environment antifoulant, the toxicity and environmental
      impacts of which need to be further investigated. Thus, this study examined the
      toxicity of DCOIT on Nile tilapia (Oreochromis niloticus), including its effects
      on behavior, respiration and energy metabolism as well as the role of endoplasmic
      reticulum stress (ER stress) in mediating its toxicity and metabolic changes. The
      changes in fish behavior, respiration, neuronal signal transmission, energy
      metabolism, ER stress, and liver histology were examined via acute (4 days) and
      chronic (28 days) exposures to 0, 3, 15, 30 MUg/L DCOIT in vivo. Additionally, ER
      stress levels were measured in 24-h periods of hepatocyte exposure to 0, 3, 15,
      30 and 300 MUg/L DCOIT in vitro. The hyper-locomotor activities decreased, but
      the respiration rate increased after a 4-day acute exposure period, indicating
      that DCOIT exposure altered fish energy metabolism. After acute exposure at a low
      DCOIT concentration, the activation of ER stress induced triglyceride
      accumulation in the liver. After chronic exposure for 28 days, the prolonged ER
      stress induced a series of pathological cellular changes. At the cellular level,
      exposure to a high DCOIT concentration induced ER stress in the hepatocytes. In
      addition, as a neurotoxin, DCOIT has the potential to disrupt the
      neurotransmission of the cholinergic system, resulting in motor behavior
      disruption. This study demonstrates that DCOIT plays a role in time- and
      concentration-dependent toxicity and that changes in lipid metabolism are
      directly related to endoplasmic reticulum function after exposure to an
      antifouling agent. This work advances the understanding of the toxic mechanism of
      DCOIT, which is necessary for its evaluation.

PMID- 30097283
TI  - Field-based emission measurements of biomass burning in typical Chinese built-in
      place stoves.
AB  - Residential combustion emission contributes significantly to ambient and indoor
      air pollution in China; however, this pollution source is poorly characterized
      and often overlooked in national pollution control policies. Few studies, and
      even fewer field-based investigations, have evaluated pollutant emissions from
      indoor biomass burning. One significant feature of Chinese household biofuel
      stoves is that many are built on site. In this study, 112 tests were conducted to
      investigate pollutant emission factors and variations for 11 fuel-stove
      combinations in actual use in the field. Results showed that, compared to those
      emission tests under controlled fuel burning conditions, EFs of methane, sulfur
      dioxide, particulate matter, and organic carbon from the field-based uncontrolled
      tests were higher, but carbon monoxide, nitrogen oxides, and elemental carbon
      were not significantly different. Controlled burning tests may be
      unrepresentative of real-world fuel burning. Pollutant emissions from
      uncontrolled burning tests had much higher variations compared with controlled
      tests. Most pollutant emissions from indoor straw burning are higher than that in
      open burning, except nitrogen oxides. The typical built-in-place home stoves in
      China had low efficiencies and high pollutant emissions that were rated as Tier 0
      (the worst) or Tier 1 of a four-tier scale according to the International
      Organization for Standardization, International Workshop Agreement 11-2012.
      Effective interventions are expected to lower pollutant emissions from
      residential combustion to improve air quality and to protect human health.

PMID- 30097284
TI  - Effect of sample holding time on bioaccessibility and sediment ecotoxicological
      assessments.
AB  - The ecotoxicological effects of hydrophobic organic compound (HOC) contamination
      in sediment are often assessed using laboratory exposures of cultured
      invertebrates to field-collected sediment. The use of a sediment holding time
      (storage at 4  degrees C) between field sampling and the beginning of the
      bioassay is common practice, yet the effect of holding time on the reliability of
      bioassay results is largely unknown, especially for current-use HOCs, such as
      pyrethroid insecticides. Single-point Tenax extraction can be used to estimate
      HOC concentrations in the rapidly desorbing phase of the organic carbon fraction
      of sediment (i.e., bioaccessible concentrations), which relate to sediment
      toxicity and bioaccumulation in invertebrates. In this study, repeated
      measurements of bioaccessible concentrations (via Tenax), were made as a function
      of sediment holding time using pyrethroid-contaminated field sediment, and
      Hyalella azteca 10-d survival and growth was measured concurrently for
      comparison. Similarly, bioaccessible concentrations and 14-d bioaccumulation were
      measured in Lumbriculus variegatus as a comparison using the legacy HOCs,
      polychlorinated biphenyls (PCBs). While the bioaccessible and bioaccumulated PCB
      concentrations did not change significantly through 244 d of holding time, the
      bioaccessible pyrethroid concentrations were more varied. Depending on when
      pyrethroid-contaminated sediments were sampled, the bioaccessible pyrethroid
      concentrations showed first-order loss with half-lives ranging from 3 to 45 d of
      holding, or slower, linear decreases in concentrations up to 14% decrease over
      180 d. These findings suggest that at least for some contaminants in sediments,
      holding the sediments prior to bioassays can bias toxicity estimates.

PMID- 30097285
TI  - Essential role of suppressor of cytokine signaling 1 (SOCS1) in hepatocytes and
      macrophages in the regulation of liver fibrosis.
AB  - The hepatic fibrogenic response is a protective mechanism activated by hepatocyte
      damage and is resolved upon elimination of the cause. However, persistent
      injuries cause liver fibrosis (LF) to evolve into cirrhosis, which promotes the
      development of hepatocellular carcinoma (HCC). Development of efficient
      treatments for LF requires better understanding the underlying molecular
      pathogenic mechanisms. The loss of suppressor of cytokine signaling 1 (SOCS1)
      expression promotes LF and HCC in human and mice, but the underlying mechanisms
      remain unclear. SOCS1 is a key regulator of immune cell activation. To
      investigate the anti-fibrogenic functions of SOCS1 in hepatocytes and
      macrophages, we generated mice lacking SOCS1 in hepatocytes (Socs1fl/flAlbCre) or
      macrophages (Socs1fl/flLysMCre) and evaluated hepatic fibrogenic response to
      carbon tetrachloride (CCl4). Socs1fl/flAlbCre and Socs1fl/flLysMCre mice showed
      severe LF characterized by increased collagen deposition, hydroxyproline content,
      myofibroblast accumulation along with elevated expression of Acta2 and Col1a1
      genes. CCl4 treatment triggered significant damage to hepatocytes in
      Socs1fl/flAlbCre mice but not in Socs1fl/flLysMCre mice. In both mice CCl4
      treatment reduced the expression of Mmp2 and increased the expression of Timp1.
      SOCS1 deficiency in hepatocytes or macrophages did not affect Il6, Tnfa or Tgfb,
      but diminished Infg and augmented Pdgfb expression. Both Socs1fl/flAlbCre and
      Socs1fl/flLysMCre livers showed increased mononuclear cell infiltration
      accompanied by elevated Ccl2 expression. Our findings show that SOCS1 exerts non
      redundant functions in hepatocytes and macrophages to regulate the hepatic
      fibrogenic response possibly through limiting hepatocyte damage and the
      inflammatory response of macrophages, and support the idea of exploiting SOCS1 in
      LF treatment.

PMID- 30097286
TI  - Type 3 cytokines in liver fibrosis and liver cancer.
AB  - The type 3 cytokines IL-17 and IL-22 play a crucial, well synchronized
      physiological role in wound healing and repairing tissue damage due to infections
      or injury at barrier surfaces. These cytokines act on epithelial cells to induce
      secretion of early immune mediators, recruitment of inflammatory cells to the
      site of injury, and to trigger tissue repair mechanisms. However, if the damage
      persists or if these cytokines are dysregulated, then they contribute to a number
      of inflammatory pathologies, autoimmune conditions and cancer. The liver is a
      multifunctional organ that plays an essential role in metabolism, detoxification,
      and immune surveillance. It is also exposed to a variety of pathogens, toxins and
      injuries. Over the past decade, IL-17 and IL-22 have been implicated in various
      aspects of liver inflammation. IL-17 is upregulated in chronic liver injury and
      associated with liver disease progression. In contrast, IL-22 was shown to be
      hepatoprotective during acute liver injury but exhibited inflammatory effects in
      other models. Furthermore, IL-22 and IL-17 are both associated with poor
      prognosis in liver cancer. Finally, the regulatory mechanisms governing the
      physiological versus the pathological role of these two cytokines during acute
      and chronic liver injury remain poorly understood. In this review, we will
      summarize the current state of knowledge about IL-17 and IL-22 in wound healing
      during acute and chronic liver injury, their contribution to pathogenesis, their
      regulation, and their role in the transition from advanced liver disease to liver
      cancer.

PMID- 30097287
TI  - Shock waves: A non-shocking way for targeted therapies?: Reply to comments on
      "Shock wave-induced permeabilization of mammalian cells".

PMID- 30097288
TI  - Exploring the Telepsychiatry Experience: Primary Care Provider Perception of the
      Michigan Child Collaborative Care (MC3) Program.
AB  - Pediatric mental healthcare is a growing component of primary care practice.
      However, there is a lack of access to mental health services, particularly Child
      and Adolescent Psychiatrists. The Michigan Child Collaborative Care (MC3) Program
      is a telepsychiatry service that offers embedded behavioral health consultants
      within primary care practices, telephonic consultation, video consultation and
      embedded care. Primary care provider (PCP) utilization of telepsychiatry services
      is predicated on perceiving the consultation service as user-friendly, helpful,
      and feasible in their practice. In this study, a simple survey of PCPs was
      conducted over a 5-year period to assess PCP attitudes and perceptions regarding
      MC3 consultation, including measures of efficiency, user-friendliness, and
      confidence in providing mental healthcare. The survey contained 4 items, 2
      quantitative and 2 qualitative, and took less than 2 minutes to complete. 649
      responses were received out of 1475 total possible responses (44% response rate).
      Common themes elicited from the qualitative items included perception of improved
      patient care for youth with mental illness (45.3%), improved comfort and
      confidence in caring for youth with mental illness (30.9%), greater comfort with
      the prescribing and monitoring of psychotropics (25.9%) and improved access to
      mental healthcare for youth (23.1%). PCPs strongly agreed that MC3 was user
      friendly, efficient, and enhanced their confidence in managing pediatric mental
      health concerns. This study demonstrates that the MC3 Telepsychiatry Program is
      well accepted by PCPs with self-reported improvements in providing mental
      healthcare to patients. Future research should explore how PCP perception impacts
      PCP practice, knowledge, as well as outcomes for patients and families
      longitudinally.

PMID- 30097289
TI  - Erratum to "Demonstrating conversion in the clinic" [Psychosomatics 58/1 (2017)
      97-98].

PMID- 30097290
TI  - Ultraviolet radiation modulates C:N stoichiometry and biomass allocation in Fagus
      sylvatica saplings cultivated under elevated CO2 concentration.
AB  - Under the conditions of ongoing climate change, terrestrial ecosystems will be
      simultaneously exposed to a permanent rise in atmospheric CO2 concentration and
      increasing variability of such environmental factors as temperature,
      precipitation, and UV radiation. This will result in numerous interactions. The
      interactive effects caused by exposure to such multiple environmental factors are
      not yet well understood. We tested the hypotheses that enhanced UV radiation
      reduces the stimulatory effect of elevated CO2 concentration on plant biomass
      production and that it alters biomass allocation in broadleaved European beech
      (Fagus sylvatica L.) saplings. Our results after 2 years of exposure confirmed
      interactive effects of CO2 concentration and UV radiation on biomass production,
      and particularly on biomass allocation to roots and aboveground biomass. The
      strongest stimulatory effect of elevated CO2 on aboveground biomass and roots was
      found under ambient UV radiation, while both low and high UV doses reduced this
      stimulation. Nitrogen content in the roots and the distribution of nitrogen among
      leaves and roots were also significantly affected by interaction of CO2
      concentration and UV radiation. The observed changes in leaf and root C:N
      stoichiometry were associated with altered morphological traits, and particularly
      with a change in the proportion of fine roots. As the biomass allocation and
      especially the proportion of fine roots can play an important role in effective
      water and nutrient use and acclimation to future climates, it is essential to
      obtain a deeper understanding of the links between C:N stoichiometry and biomass
      accumulation.

PMID- 30097291
TI  - Cortisol regulates immune and metabolic processes in murine adipocytes and
      macrophages through HTR2c and HTR5a serotonin receptors.
AB  - Epidemiological studies implicate stress as an important factor contributing to
      the increasing prevalence of metabolic disorders. Studies have correlated
      visceral obesity and atherosclerosis with hyper-cortisolemia, a sequela of
      chronic psychological stress in humans and animals. Although several hormonal
      markers of stress have been associated with various metabolic disorders, the
      mechanism by which these hormones alter metabolic functions have not been
      established. We used an in vitro model system, culturing 3T3-L1 pre-adipocytes
      and RAW 264.7 macrophages in the presence or absence of cortisol, to analyze cell
      signaling pathways mediating changes in metabolic functions. Our analysis
      revealed that cortisol up-regulated the expression and function of two serotonin
      (S) receptors, HTR2c and HTR5a. HTR2c and HTR5a were also directly involved in
      mediating cortisol enhanced adipogenesis when pre-adipocytes were cultured alone
      or in the presence of macrophages. Finally, cortisol treatment of pre-adipocytes
      co-cultured with macrophages enhanced adipogenesis in both macrophages and pre
      adipocytes.

PMID- 30097293
TI  - LAG3+ Regulatory T Cells Restrain Interleukin-23-Producing CX3CR1+ Gut-Resident
      Macrophages during Group 3 Innate Lymphoid Cell-Driven Colitis.
AB  - Interleukin-22 (IL-22)-producing group 3 innate lymphoid cells (ILC3) maintains
      gut homeostasis but can also promote inflammatory bowel disease (IBD). The
      regulation of ILC3-dependent colitis remains to be elucidated. Here we show that
      Foxp3+ regulatory T cells (Treg cells) prevented ILC3-mediated colitis in an IL
      10-independent manner. Treg cells inhibited IL-23 and IL-1beta production from
      intestinal-resident CX3CR1+ macrophages but not CD103+ dendritic cells. Moreover,
      Treg cells restrained ILC3 production of IL-22 through suppression of CX3CR1+
      macrophage production of IL-23 and IL-1beta. This suppression was contact
      dependent and was mediated by latent activation gene-3 (LAG-3)-an immune
      checkpoint receptor-expressed on Treg cells. Engagement of LAG-3 on MHC class II
      drove profound immunosuppression of CX3CR1+ tissue-resident macrophages. Our
      study reveals that the health of the intestinal mucosa is maintained by an axis
      driven by Treg cells communication with resident macrophages that withhold
      inflammatory stimuli required for ILC3 function.

PMID- 30097294
TI  - [Guidelines for methacholine provocation testing].
AB  - Bronchial challenge with the direct bronchoconstrictor agent methacholine is
      commonly used for the diagnosis of asthma. The "Lung Function" thematic group of
      the French Pulmonology Society (SPLF) elaborated a series of guidelines for the
      performance and the interpretation of methacholine challenge testing, based on
      French clinical guideline methodology. Specifically, guidelines are provided with
      regard to the choice of judgment criteria, the management of deep inspirations,
      and the role of methacholine bronchial challenge in the care of asthma, exercise
      induced asthma, and professional asthma.

PMID- 30097292
TI  - Electron-Microscopy-Based Epitope Mapping Defines Specificities of Polyclonal
      Antibodies Elicited during HIV-1 BG505 Envelope Trimer Immunization.
AB  - Characterizing polyclonal antibody responses via currently available methods is
      inherently complex and difficult. Mapping epitopes in an immune response is
      typically incomplete, which creates a barrier to fully understanding the humoral
      response to antigens and hinders rational vaccine design efforts. Here, we
      describe a method of characterizing polyclonal responses by using electron
      microscopy, and we applied this method to the immunization of rabbits with an HIV
      1 envelope glycoprotein vaccine candidate, BG505 SOSIP.664. We detected known
      epitopes within the polyclonal sera and revealed how antibody responses evolved
      during the prime-boosting strategy to ultimately result in a neutralizing
      antibody response. We uncovered previously unidentified epitopes, including an
      epitope proximal to one recognized by human broadly neutralizing antibodies as
      well as potentially distracting non-neutralizing epitopes. Our method provides an
      efficient and semiquantitative map of epitopes that are targeted in a polyclonal
      antibody response and should be of widespread utility in vaccine and infection
      studies.

PMID- 30097295
TI  - Gender disparities in Zika virus knowledge in a potentially at-risk population
      from suburban New York City.
AB  - Zika virus is an emerging infection transmitted in multiple ways. In 2016 we
      assessed the level of knowledge about Zika virus transmission in an underserved,
      predominantly Hispanic, mixed gender population living in suburban New York City,
      many of whom potentially travel to affected regions. Based on a convenience
      sample of 147 participants, 134 (91%) were aware of Zika virus transmission by
      mosquitoes; 116 (79%) knew about transmission from a pregnant female to the
      fetus; and 89 (61%) were aware of sexual transmission. Age, marital status,
      education, and native language were unrelated to knowledge (P > 0.10). Women,
      however, were significantly more likely than men to know about sexual
      transmission (P = 0.023) and about maternal transmission to the fetus (P =
      0.044). Travel to Zika virus endemic areas was unrelated to level of knowledge (P
      = 0.40). Greater awareness of the risk of sexual transmission of Zika virus is
      needed for at risk populations in the US, especially for males.

PMID- 30097297
TI  - Activity of plazomicin in combination with other antibiotics against multidrug
      resistant Enterobacteriaceae.
AB  - Plazomicin is a next-generation aminoglycoside that was approved by the US FDA in
      June 2018 for the treatment of complicated urinary tract infections (cUTIs),
      including pyelonephritis due to Escherichia coli, Klebsiella pneumoniae,
      Enterobacter cloacae and Proteus mirabilis. Plazomicin is active against multi
      drug resistant (MDR) Enterobacteriaceae, where combination therapy is often used
      to treat infections caused by these pathogens. To determine synergy with other
      antibiotics, plazomicin was combined with antibiotics in checkerboard assays
      against MDR Enterobacteriaceae, including isolates with resistance to
      aminoglycosides and beta-lactams; 10 Escherichia coli isolates, 8 Klebsiella spp.
      isolates, 10 Enterobacter spp. isolates, and 2 Citrobacter freundii isolates were
      evaluated. Plazomicin had potent activity against MDR Enterobacteriaceae,
      including aminoglycoside-resistant strains, with MIC ranges of 0.5 - 2 MUg/mL
      against E. coli isolates, 0.12 - 8 MUg/mL against Klebsiella spp. isolates, 0.25 
      2 MUg/mL against Enterobacter spp. isolates, and 0.06 - 0.25 MUg/mL against C.
      freundii isolates. Synergy between plazomicin and piperacillin/tazobactam or
      ceftazidime was observed by checkerboard studies and confirmed by time-kill
      assays. No combination showed antagonism. These studies indicate that plazomicin
      has potential as a monotherapy and as combination therapy for treating serious
      Gram-negative infections caused by MDR Enterobacteriaceae.

PMID- 30097296
TI  - Performance of CHROMID(r) Colistin R agar, a new chromogenic medium for screening
      of colistin-resistant Enterobacterales.
AB  - Recent emergence of transferable plasmid-borne colistin resistance (mcr genes)
      raised fear for pan-resistance. We evaluated the performance of a new chromogenic
      medium [CHROMID(r) Colistin R agar (COLR)] for the screening of colistin
      resistant Enterobacterales. Specificity was evaluated using 89 rectal swabs and
      89 stools prospectively collected. COLR sensitivity was evaluated by seeding 59
      negative clinical samples artificially contaminated (105 CFU/mL) with 59 colistin
      resistant Enterobacterales, including 20 mcr-1-positive strains. Twelve samples
      with an Enterobacterales with nonintrinsic resistance to colistin were recovered
      during the specificity study, including one mcr-1-positive Escherichia coli,
      representing a 6.7% prevalence of colistin resistance in fecal carriage. Overall,
      specificity was 100.0% [95% CI: 97.8-100.0] and sensitivity yielded 88.1% [95%
      CI: 77.5-94.1]. False negatives corresponded to 3 Enterobacter spp. (MIC>64
      mg/L), 2 Salmonella spp. (MIC = 16 mg/L), 1 E. coli (MIC = 4 mg/L), and 1 K.
      pneumoniae (MIC = 8 mg/L). COLR appears to be a sensitive and specific
      chromogenic agar for screening colistin-resistant Enterobacterales, including
      those carrying mcr-1 gene.

PMID- 30097298
TI  - Diastolic Dysfunction Assessed Using Contemporary Guidelines and Prognosis
      Following Myocardial Infarction.
AB  - BACKGROUND: Recent American Society of Echocardiography and European Association
      of Cardiovascular Imaging guidelines for the assessment of diastolic dysfunction
      (DD) recommend a simplified approach with four key variables incorporated into a
      novel diagnostic algorithm. The aim of this study was to assess the prognostic
      value of significant DD assessed using the algorithm recommended in the 2016
      American Society of Echocardiography and European Association of Cardiovascular
      Imaging guidelines (DD2016) in comparison with the prognostic value of
      significant DD assessed using the 2009 guidelines (DD2009) as well as the
      individual parameters incorporated in the 2016 algorithm. METHODS: Retrospective
      data on 419 consecutive patients with first ever myocardial infarction were
      included. Doppler echocardiography was performed within 24 hours of admission in
      all patients. Significant DD was defined as grade 2 or 3 DD. The primary outcome
      measure was composite major adverse cardiovascular events (MACEs), comprising
      death, myocardial infarction, and heart failure. RESULTS: At a median follow-up
      of 24 months, there were 61 MACEs. On Kaplan-Meier analysis, DD2016 showed a
      better association with MACEs than DD2009 (log-rank chi2 = 21.01 [P < .001] vs
      13.13 [P = .001]). On Cox proportional-hazards multivariate analysis
      incorporating significant clinical predictors and left ventricular ejection
      fraction, DD2016 (hazard ratio, 2.22; 95% CI, 1.25-3.98; P = .007) was the
      strongest independent predictor of MACEs, whereas DD2009 (hazard ratio, 1.63; 95%
      CI, 0.95-2.80; P = .074) was not a significant predictor. Of the four key
      diastolic parameters, only left atrial volume index was independently associated
      with MACEs (hazard ratio, 1.79; 95% CI, 1.02-3.14; P = .041) when included in a
      Cox proportional-hazards multivariate model incorporating significant clinical
      predictors and left ventricular ejection fraction, although the association was
      weaker than DD2016. Intermodel comparisons with model chi2 and Harrell's C
      statistic were satisfactory for DD2016. CONCLUSIONS: Significant DD assessed
      using the 2016 American Society of Echocardiography and European Association of
      Cardiovascular Imaging guidelines is a robust independent predictor of clinical
      outcomes following myocardial infarction and compares favorably with DD2009 as
      well as the individual parameters incorporated in the novel 2016 algorithm.

PMID- 30097299
TI  - Focused Cardiac Ultrasound by Nurses in Rural Vietnam.
AB  - BACKGROUND: Multiple studies investigating the use of focused cardiac ultrasound
      (FCU) in lower and middle-income countries and in medically underserved areas of
      the United States have demonstrated utility in echocardiographic screening
      algorithms performed by a variety of operators at different levels of training.
      No study to date has employed previously untrained nurses in a medically
      underserved setting to identify older adults with cardiac disorders. The aim of
      this study was to assess the accuracy of nurse-performed FCU to screen adult
      subjects at a village health center in Vietnam. METHODS: Vietnamese nurses (N =
      8) underwent structured training conducted by sonographers and physicians during
      an outreach event sponsored by the American Society of Echocardiography Education
      and Research Foundation. The nurses were trained to detect abnormalities from a
      single echocardiographic view (parasternal long-axis) with a laptop-sized device
      and underwent pre- and posttraining testing. Following training, cardiac
      ultrasound examinations were performed on subjects >50 years of age at a village
      health center. First, the nurses performed focused cardiac ultrasound using two
      dimensional and color Doppler imaging in the parasternal long-axis view using the
      M7 device and recorded their assessments. Two-dimensional color and spectral
      Doppler echocardiography was thereafter performed using the same machine by a
      sonographer (n = 5) or a Vietnamese echocardiography-trained cardiologist (n =
      1). Interviews and electrocardiography were performed at the time of FCU.
      RESULTS: Each nurse improved from pre- to posttraining (average improvement in
      correct answers, 21%; range, 2%-31%). During the scanning phase, nurses'
      sensitivity, specificity, and accuracy for identifying subjects with any
      abnormality were 51.5% (85 of 165), 78.1% (82 of 105) and 61.9%, respectively.
      There were 60 subjects with significant findings (22.2%); all of these subjects
      had significant abnormalities visible on parasternal long-axis images. Overall
      sensitivity, specificity, and accuracy for identifying subjects with major
      abnormalities were 83.3% (50 of 60), 78.1% (164 of 210), and 78.6%, respectively.
      Nurse-performed FCU demonstrated much higher sensitivity with lower specificity
      than electrocardiography alone. The combination of nurse-performed FCU plus ECG
      identified all of the significant findings on echocardiography and increased
      accuracy to 91.5%. CONCLUSIONS: Nurses with no prior echocardiographic experience
      and with limited training can identify patients with significant cardiac
      abnormalities using FCU with acceptable accuracy. Screening strategies involving
      FCU may play a role in improving access to health care and triage in underserved
      areas.

PMID- 30097301
TI  - Telemedicine's Role in Addressing the Opioid Epidemic.

PMID- 30097300
TI  - Diagnosis of Isolated Cleft Mitral Valve Using Three-Dimensional
      Echocardiography.
AB  - BACKGROUND: The prevalence of isolated cleft mitral valve (MV; no concomitant
      congenital heart disease or degenerative MV disease) with significant mitral
      regurgitation (MR) diagnosed using two-dimensional echocardiography (2DE) has
      been reported to be very low. Three-dimensional echocardiography (3DE) has
      enabled a more comprehensive visualization of the MV and detailed understanding
      of the mechanisms of MR and can potentially reveal isolated cleft MV that is not
      recognized with 2DE. The aim of this study was to determine, using 3DE, the
      prevalence, location, and associated MV annular and left ventricular
      characteristics of isolated cleft MV, in the absence of associated congenital
      heart disease, in patients with significant MR. METHODS: A total of 1,092
      patients with unexplained moderate or greater MR on two-dimensional transthoracic
      echocardiography who were referred for three-dimensional transesophageal
      echocardiography between 2005 and 2017 (n = 626) were retrospectively studied.
      Left ventricular dimensions and function were determined, and quantitative MR
      assessment and three-dimensional analysis of the MV annulus was performed.
      RESULTS: Twenty-one patients (prevalence 3.3%) were diagnosed with isolated cleft
      MV using three-dimensional transesophageal echocardiography but not 2DE. The
      majority of these patients (n = 16) were noted to have anterior cleft MVs, with
      most located in the mid-A1 (n = 10) or mid-A3 (n = 5) scallops. Posterior clefts
      were less common (n = 5) and occurred at the site of the natural scallop
      indentations (three between P1 and P2 and two between P2 and P3). Among patients
      with either anterior or posterior MV cleft, there were no differences in left
      ventricular ejection fraction or three-dimensional MV geometry (annular distance,
      height, circumference, and area). There was a trend toward worse MR severity in
      patients with anterior cleft MV. CONCLUSIONS: In patients with otherwise
      unexplained significant MR referred for transesophageal echocardiography, 3DE
      uncovered a considerably higher prevalence of isolated cleft MV than previously
      reported by 2DE, with the majority located in the anterior MV. Although the
      annular geometry was similar between patients with anterior and posterior cleft
      MVs, a trend toward more severe MR in anterior clefts may reflect underlying
      abnormalities in the embryologic development of the anterior MV leaflet.
      Evaluation of MV pathology is improved by 3DE, which should be used routinely in
      the setting significant MR.

PMID- 30097303
TI  - Intraoperative initiation of a modified ARDSNet protocol increases survival of
      septic patients with severe acute respiratory distress syndrome.
AB  - PURPOSE: To assess the intraoperative initiation and feasibility of a modified
      NIH-NHLBI ARDS Network Mechanical Ventilation Protocol (mARDSNet protocol) in
      septic patients with severe ARDS. MATERIALS AND METHODS: This prospective
      observational study included consecutive adult septic patients with severe ARDS
      who underwent emergency abdominal surgery prior to intensive care unit (ICU)
      admission. The primary outcome was survival to hospital discharge and at 90 days.
      Secondary outcomes were intraoperative adverse events and ICU length of stay.
      RESULTS: Seven patients were included. A statistically significant difference in
      lung compliance [epsilon=0.150, F(1.053, 3.158)=31.098, p=0.010] and driving
      pressure [epsilon=0.263, F(1.844, 5.532)=7.042, p=0.031] was observed with time,
      while plateau pressure did not changed significantly during surgery
      [epsilon=0.322, F(2.256, 6.769)=1.920, p=0.219]. Also, PEEP values were
      constantly increased during surgery [epsilon=0.252, F(1.766, 5.297)=9.994,
      p=0.017], with the highest values being observed towards to the end of the
      procedure. No intraoperative adverse events were observed. Mean (+/-SD) ICU
      length of stay was 10.43 (+/-2.64) days, while all patients survived to hospital
      discharge and at 90 days. CONCLUSIONS: The intraoperative implementation of our
      mARDSNet protocol is feasible and may increase the survival of septic patients
      with severe ARDS if initiated prior to ICU admission.

PMID- 30097302
TI  - Evaluation of the equine mental foramen block: cadaveric and in vivo injectate
      diffusion.
AB  - OBJECTIVE: To describe injectate diffusion for two equine mental foramen block
      techniques. STUDY DESIGN: Descriptive anatomic study. ANIMALS: A total of 12
      equine heads and three live horses. METHODS: Equine heads were longitudinally
      sectioned to create 24 hemi-heads for testing two mental foramen block techniques
      (T1 and T2) and two injectate volumes (3 and 5 mL) of mixed dye and contrast
      medium. T1 needles were directed rostrocaudally into the mental foramen for 3 cm,
      and T2 needles were directed dorsolaterally to ventromedially into the foramen
      for 1 cm. Hemi-heads were randomly assigned one injection technique and volume.
      Radiographs evaluated needle tip positioning, distance traveled by injectate and
      injectate diffusion pattern. Specimens were dissected to measure the length of
      circumferential nerve staining. The more effective technique was tested in three
      live horses and evaluated via computed tomography. Summary statistics described
      results. RESULTS: Neither injection technique nor injectate volume had a
      significant impact on circumferential nerve staining. Circumferential nerve
      staining, median (range), was 15 (0-33) mm for T1 and 10 (0-42) mm for T2.
      Injectate diffusion patterns revealed that injectate was more likely to thread
      alongside the inferior alveolar nerve for T1 (9/12) and bolus around the rostral
      inferior alveolar nerve for T2 (9/12). Bolus diffusion patterns were associated
      with increased circumferential nerve staining >=1 cm (9/24) when compared with
      thread patterns (6/24). Diffusion of injectate within the mandibular canal was
      greater with 5 than 3 mL. In vivo testing of T2 with 5 mL injectate resulted in
      decreased incidence of circumferential nerve staining >=1 cm [median (range) 5 (0
      14) mm]. CONCLUSION AND CLINICAL RELEVANCE: T2 created an injection diffusion
      pattern more likely to result in circumferential nerve staining >=1 cm, but the
      low incidence of in vivo circumferential nerve staining >=1 cm suggests that
      block efficacy may vary.

PMID- 30097304
TI  - Face Space Representations in Deep Convolutional Neural Networks.
AB  - Inspired by the primate visual system, deep convolutional neural networks (DCNNs)
      have made impressive progress on the complex problem of recognizing faces across
      variations of viewpoint, illumination, expression, and appearance. This
      generalized face recognition is a hallmark of human recognition for familiar
      faces. Despite the computational advances, the visual nature of the face code
      that emerges in DCNNs is poorly understood. We review what is known about these
      codes, using the long-standing metaphor of a 'face space' to ground them in the
      broader context of previous-generation face recognition algorithms. We show that
      DCNN face representations are a fundamentally new class of visual representation
      that allows for, but does not assure, generalized face recognition.

PMID- 30097305
TI  - Priors in Animal and Artificial Intelligence: Where Does Learning Begin?
AB  - A major goal for the next generation of artificial intelligence (AI) is to build
      machines that are able to reason and cope with novel tasks, environments, and
      situations in a manner that approaches the abilities of animals. Evidence from
      precocial species suggests that driving learning through suitable priors can help
      to successfully face this challenge.

PMID- 30097306
TI  - Time for change: Fitness and strength can be improved and sustained in
      adolescents with low motor competence.
AB  - BACKGROUND: There are few exercise interventions focused on adolescents with low
      motor competence and most interventions are short with little follow up and
      engagement over time. METHODS AND PROCEDURES: Fifty-eight adolescents with low
      motor competence (39 males, Mean Age = 13.6, SD = 1.4 years) attended an exercise
      clinic twice a week for each 13 week program. Two programs ran each year, and
      participants attended for as long as they felt progress was made or they turned
      18 years of age. Performance on the Multistage Fitness Test (MSFT), Curl-ups,
      Grip Strength, 1RM Leg press and Chest Press, Vertical Jump and Standing Broad
      Jump (SBJ) were recorded pre and post each program for up to six years. Linear
      Mixed Modelling (LMM) determined changes in fitness measures over time whilst
      adjusting for gender, age and Neuromuscular Developmental Index (McCarron, 1997).
      RESULTS: All fitness measures increased, and specifically four of the seven
      fitness outcomes showed significant improvement over time (MSFT,p =  0.011; curl
      ups, p < 0.001, grip strength p = 0.003, and SBJ p = 0.006). CONCLUSION: An
      individually tailored regular exercise program in a supportive environment can
      achieve exercise adherence and sustainable improvements in fitness outcomes for
      adolescents with low motor competence. Future research should consider the
      addition of a comparison LMC control group to increase understanding of the
      intervention effect.

PMID- 30097307
TI  - Visual tracking behaviour of two-handed catching in boys with developmental
      coordination disorder.
AB  - BACKGROUND: Developmental coordination disorder (DCD) is a motor learning
      disability that affects coordination resulting in an inability to perform
      movement skills at an age appropriate level. One area suspected to contribute to
      the movement difficulties experienced are deficits in visuomotor control. AIMS:
      This study investigated visual tracking behaviour during catching in children
      with DCD. METHODS AND PROCEDURES: Twenty-four boys completed the study: 11 with
      DCD (9.43 years +/-0.73) and 13 controls (9.16 years +/- 0.68). Participants
      performed 10 central catching trials, with the best five used to evaluate
      tracking behaviour and motor responses. OUTCOMES AND RESULTS: Prior to ball
      release, the DCD group exhibited more fixations (p = 0.043) of lesser duration (p
      = 0.045). During flight, the DCD group took longer to initiate smooth pursuit (p
      = 0.003) however, once initiated, both groups were effectively able to maintain
      smooth pursuit. Despite initial delays, these had no impact on movement
      initiation time (p = 0.173), however, movement time was significantly slower in
      the DCD group (p = 0.031). CONCLUSIONS AND IMPLICATIONS: The results of this
      study demonstrate that catching performance in children with DCD likely reflect a
      combination of errors in attending to visual information and movement
      organisation.

PMID- 30097308
TI  - Complications and trauma sequelae.

PMID- 30097309
TI  - Timing of surgery for hip fractures in the elderly: A retrospective cohort study.
AB  - INTRODUCTION: Although early surgery for elderly patients with hip fracture is
      recommended in existing clinical guidelines, the results of previous studies are
      inconsistent. The aim of this study was to compare postoperative outcomes of
      early and delayed surgery for elderly patients with hip fracture. MATERIALS AND
      METHODS: In this retrospective study using a national inpatient database in
      Japan, patients aged 65 years or older who underwent surgery for hip fracture
      between July 2010 and March 2014 were included. Early surgery was defined as
      surgery on the day or the next day of admission. Assessed outcomes included death
      within 30 days and hospital-acquired pneumonia. RESULTS: In this cohort, 47,073
      (22.5%) patients underwent surgery for hip fractures within two days of admission
      (early surgery group) and 161,805 (77.5%) underwent surgery for hip fractures
      thereafter (delayed surgery group). Early surgery was significantly associated
      with lower odds for hospital-acquired pneumonia (odds ratio, 0.42; 95% confidence
      interval, 0.25-0.69) and pressure ulcers (odds ratio, 0.56, 95%CI: 0.33-0.96, p =
      0.035), but was not associated with 30-day mortality (odds ratio, 0.96; 95%
      confidence interval, 0.49-1.86) or pulmonary embolism (odds ratio, 1.62, 95%CI:
      0.58-4.52, p = 0.357). CONCLUSIONS: These results support current guidelines,
      which recommend early surgery for elderly hip fractures patients.

PMID- 30097310
TI  - Using Naive Bayes Classifier to predict osteonecrosis of the femoral head with
      cannulated screw fixation.
AB  - Predictive models permitting personalized prognostication for patients with
      cannulated screw fixation for the femoral neck fracture before operation are
      lacking. The objective of this study was to train, test, and cross-validate a
      Naive Bayes Classifier to predict the occurrence of postoperative osteonecrosis
      of cannulated screw fixation before the patient underwent the operation. The data
      for the classifier model were obtained from a ambispective cohort of 120 patients
      who had undergone closed reduction and cannulated screw fixation from January
      2011 to June 2013. Three spatial displaced parameters of femoral neck:
      displacement of centre of femoral head, displacement of deepest of femoral head
      foveae and rotational displacement were measured from preoperative CT scans using
      a 3-dimensional software. The Naive Bayes Classifier was modelled with age,
      gender, side of fractures, mechanism of injury, preoperative traction, Pauwels
      angle and the three spatial parameters. After modelling, the ten-fold cross
      validation method was used in this study to validate its performance. The ten
      fold cross-validation method uses the whole dataset to be trained and tested by
      the given algorithm. Two of the three spatial parameters of femoral neck
      (displacement of center of femoral head and rotational displacement) were
      included successfully in the final Naive Bayes Classifier. The Classifier
      achieved good performance of the accuracy (74.4%), sensitivity (74.2%),
      specificity (75%), positive predictive value (92%), negative predictive value
      (42.9%) and AUC (0.746). We showed that the Naive Bayes Classifier have the
      potential utility to be used to predict the osteonecrosis of femoral head within
      5 years after surgery. Although this study population was restricted to patients
      treated with cannulated screws fixation, Bayesian-derived models may be developed
      for application to patients with other surgical procedures at risk of
      osteonecrosis.

PMID- 30097312
TI  - EarlyR: A Robust Gene Expression Signature for Predicting Outcomes of Estrogen
      Receptor-Positive Breast Cancer.
AB  - INTRODUCTION: Early stage estrogen receptor (ER)-positive breast cancer may be
      treated with chemotherapy in addition to hormone therapy. Currently available
      molecular signatures assess the risk of recurrence and the benefit of
      chemotherapy; however, these tests may have large intermediate risk groups,
      limiting their usefulness. METHODS: The EarlyR prognostic score was developed
      using integrative analysis of microarray data sets and formalin-fixed, paraffin
      embedded-based quantitative real-time PCR assay and validated in Affymetrix data
      sets and METABRIC cohort using Cox proportional hazards models and Kaplan-Meier
      survival analysis. Concordance index was used to measure the probability of
      prognostic score agreement with outcome. RESULTS: The EarlyR score and
      categorical risk strata (EarlyR-Low, EarlyR-Int, EarlyR-High) derived from
      expression of ESPL1, MKI67, SPAG5, PLK1 and PGR was prognostic of 8-year distant
      recurrence-free interval in Affymetrix (categorical P = 3.5 * 10-14; continuous P
      = 8.8 * 10-15) and METABRIC (categorical P < 2.2 * 10-16; continuous P < 10-16)
      data sets of ER+ breast cancer. Similar results were observed for the breast
      cancer-free interval end point. At most 13% of patients were intermediate risk
      and at least 66% patients were low risk in both ER+ cohorts. The EarlyR score was
      significantly prognostic (distant recurrence-free interval; P < .001) in both
      lymph node-negative and lymph node-positive patients and was independent from
      clinical factors. EarlyR and surrogates of current molecular signatures were
      comparable in prognostic significance by concordance index. CONCLUSION: The 5
      gene EarlyR score is a robust prognostic assay that identified significantly
      fewer patients as intermediate risk and more as low risk than currently available
      assays. Further validation of the assay in clinical trial-derived cohorts is
      ongoing.

PMID- 30097311
TI  - Bilateral Low-Dose Computed Tomography Assessment for Post-Operative Rotational
      Malalignment After Intramedullary Nailing for Tibial Shaft Fractures: Reliability
      of a Practical Imaging Technique.
AB  - INTRODUCTION: The purpose of this study is to evaluate the intra- and inter
      observer reliability of low-dose protocolled bilateral postoperative Computed
      Tomography (CT)-assessment of rotational malalignment after intramedullary
      nailing (IMN) of tibial shaft fractures. MATERIALS AND METHODS: 156 patients were
      prospectively included with tibial shaft fractures that were treated with IMN in
      a Level-I Trauma Centre. All patients underwent post-operative bilateral low-dose
      CT-assessment (effective dose of 0.03784 - 0.05768 mGy) as per hospital protocol.
      Four observers performed the validated reproducible measurements of tibial
      torsion in degrees, based on standardized techniques. The Intra-Class Coefficient
      (ICC) was calculated to evaluate intra- and inter-observer reliability. The intra
      and inter-observer reliability was categorized according to Landis and Koch.
      RESULTS: Intra-observer reliability for quantification of rotational malalignment
      on post-operative CT after IMN of tibial shaft fractures was excellent with 0.95
      (95% CI = 0.92-0.97). The overall inter-observer reliability was 0.90 (95% CI =
      0.87-0.92), also excellent according Landis and Koch. CONCLUSION: Firstly,
      bilateral post-operative low-dose -similar radiation exposure as plain chest
      radiographs- CT assessment of tibial rotational alignment is a reliable
      diagnostic imaging modality to assess rotational malalignment in patients
      following IMN of tibial shaft fractures and it allows for early revision surgery.
      Secondly, it may contribute to our understanding of the incidence-, predictors-
      and clinical relevance of post-operative tibial rotational malalignment in
      patients treated with IMN for a tibial shaft fracture, and facilitates future
      studies on this topic.

PMID- 30097313
TI  - Estimating regions of interest on the distal femur.
AB  - We investigated the ability of a statistical shape model to estimate unknown
      regions of interest related to patient-specific unicompartmental knee replacement
      design on the distal femur. Generality ranged between 0.67 and 1.03 mm,
      specificity from 0.79 to 1.07 mm, and leave-one-out root mean square estimation
      errors from 0.88 to 1.27 mm for different regions. Moderate to strong
      correlations were established between ground truths and model estimates for local
      morphological measurements on the medial and lateral condyles. Results compared
      well to similar studies in the literature, and we conclude that shape models
      might prove useful during patient-specific unicompartmental knee replacement
      design.

PMID- 30097314
TI  - Validity of the Microsoft KinectTM in assessing spatiotemporal and lower
      extremity kinematics during stair ascent and descent in healthy young
      individuals.
AB  - Stair negotiation is one of the most challenging, yet frequently encountered,
      locomotor tasks in daily life. This study is the first attempt to investigate the
      capacity of the KinectTM sensor to assess stair negotiation spatiotemporal and
      sagittal plane kinematic variables. The goal of this study was to examine the
      validity of the KinectTM v2 sensor in assessing lower extremity kinematics and
      spatiotemporal parameters in healthy young individuals; and to demonstrate its
      potential as a low-cost stair gait analysis tool. Twelve healthy participants
      ascended and descended a 3-step custom-built staircase at their preferred speed,
      as spatiotemporal parameters and kinematics were extracted simultaneously using
      the KinectTM and a three-dimensional motion analysis. Spatiotemporal measures
      included gait speed, swing phase time, and double stance time. Kinematic outcomes
      included hip, knee, and ankle joint angles in the sagittal plane. Consistency
      (ICC2,1) and absolute agreement (ICC3,1) between the two systems were assessed
      using separate interclass correlations coefficients. In addition, ensemble curves
      and associated 90% confidence intervals (CI90) were generated for the hip, knee,
      and ankle kinematics to enable between system comparisons throughout the gait
      cycle. Results showed that the KinectTM has the potential to be an effective
      clinical assessment device for sagittal plane hip and knee joint kinematics and
      for some spatiotemporal parameters during the stair gait negotiation.

PMID- 30097315
TI  - Preoperative QTc Interval is Not Associated With Intraoperative Cardiac Events or
      Mortality in Liver Transplantation Patients.
AB  - OBJECTIVES: The primary objective of this study was to determine whether liver
      transplantation recipients with preoperative prolonged corrected (QTc) intervals
      have a higher incidence of intraoperative cardiac events and/or postoperative
      mortality compared with their peers with normal QTc intervals. DESIGN: This was a
      retrospective cohort study. SETTING: Single academic hospital in New York, NY.
      PARTICIPANTS: Patients undergoing liver transplantation between 2007 and 2016.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data relating to all liver
      transplantation recipients with preoperative electrocardiograms were queried from
      an institutional anesthesia data warehouse and electronic medical records.
      Primary outcomes were a composite outcome of intraoperative cardiac events and
      postoperative mortality. Patients with a prolonged QTc interval (>450 ms for men,
      >470 ms for women) did not demonstrate an association with intraoperative cardiac
      events, 30- or 90-day mortality, in-hospital mortality, or overall mortality
      compared with recipients in the normal QTc interval group. A prolonged QTc was
      found to be associated with increased anesthesia time, surgical time, length of
      hospital stay, and incidence of fresh frozen plasma and platelets transfusion.
      CONCLUSIONS: Prolonged QTc interval is not associated with an increased incidence
      of intraoperative cardiac events or mortality in liver transplantation
      recipients. The demonstrated correlation among QTc length and Model for End-stage
      Liver Disease score, blood component requirements, surgical and anesthetic times,
      and hospital length of stay likely represents the association between QTc length
      and severity of liver disease.

PMID- 30097316
TI  - Mid-to long-term results of total hip arthroplasty after contralateral lower
      extremity amputation.
AB  - OBJECTIVE: There is limited literature concerning the outcomes and role of THA as
      a surgical option for amputee patients. The aim of this study is to determine the
      mid-to long-term survival and complication rates of cementless total hip
      arthroplasty (THA) in patients with contralateral below knee amputations.
      METHODS: A retrospective review of 54 patients with below knee amputation were
      perfomed who underwent THA for osteoarthritis of the contralateral hip over a 5
      year period between 1999 and 2014. Patients were monitored for at least 5 years
      and assessed with the Harris Hip Score and activities of daily living scale and
      by evaluating migration or osteolysis around the acetabular cup and femoral stems
      (amputee group). The amputee group was compared with a control group (non-amputee
      group) with the same number of patients. RESULTS: Differences in the Harris Hip
      Score (p = 0.021) and activities of daily living scale (p = 0.043) between the
      two groups were statistically significant lower in the amputee group at 3 months
      after surgery. However, no differences were found between the groups from 6
      months postoperatively to the last follow-up (Harris Hip Score p = 0.812,
      activities of daily living scale p = 0.885). Radiologically, any cups or stems
      showed no signs of migration or osteolysis. In the amputee group, dislocation was
      found in 1 patient 2 months after arthroplasty (p = 0.315) and long stem revision
      surgery were performed on two patients due to periprosthetic fracture (p =
      0.153). CONCLUSIONS: THA performed on the contralateral side of patients with
      below knee amputation is considered to be an effective treatment with good
      clinical and radiological results at mid-to long-term follow-up. LEVEL OF
      EVIDENCE: Level IV, therapeutic study.

PMID- 30097317
TI  - Two introduced crocodile species had changed reproductive characteristics in
      China.
AB  - The purpose of this study was to study the reproductive characteristics of the
      Nile crocodile and Siamese crocodiles after introduction into China since the
      time this occurred near the end of the last century. The data for the eggs and
      young crocodiles (recently hatched crocodiles) of two introduced species were
      collected at a Sanya crocodile breeding farm in Hainan. The characteristic
      variables of crocodile eggs were statistically analyzed, and the results
      indicated that: egg mass of the Nile and Siamese crocodile was significantly
      correlated with the egg length and width. Regression analyses were used to
      develop the linear equation between the egg length, egg width and egg mass. There
      was a strong positive correlation between the egg mass and initial weight of
      young crocodiles. The linear equation for assessing egg mass and initial weight
      of young crocodile was developed for regression analyses. There was no
      significant linear relationship between clutch size and egg characteristics.
      Mating time of the Nile crocodile in Hainan (November-April) and the spawning
      season (March-May) are significantly earlier than in the Zimbabwe region of
      origin. The average of clutch size and the mean size of eggs for Nile crocodiles
      in their native habitat is greater than the introduced region as indicated by
      analyzing data using a two-sample t-test. The Siamese crocodile spawning time was
      similar in the Hainan and Zimbabwe regions, but the size of clutches and the mean
      size of eggs in the introduced region were greater than in their native region as
      indicated by results using a two-sample t-test.

PMID- 30097318
TI  - Supplementation of freezing/thawing media with GSK3 inhibitor alsterpaullone does
      not bypass the harmful effect of cryopreservation on boar spermatozoa.
AB  - Frozen-thawed boar sperm have less motility and fertility capacity in comparison
      to fresh sperm. Glycogen Synthase Kinase 3 (GSK3) contributes to sperm motility
      in fresh semen. In addition, GSK3 inhibition in boar spermatozoa in fresh semen
      improves motility variables. The role of GSK3 on boar cryopreserved sperm,
      however, is still unknown. The hypothesis in the present study was that GSK3
      pathway inhibition by alsterpaullone (AST) could result in enhancement of the
      quality of sperm afer cryopreservation. Two different strategies were evaluated:
      i) AST supplementation to the freezing medium (AST + Cryo); ii) AST
      supplementation after sperm thawing (AST + Thaw). Sperm motility was evaluated
      using the CASA system and different sperm quality variables were evaluated using
      flow cytometry, as well as amount of GSK3 phosphorylation of thawed spermatozoa
      after 30 and 90 min incubation at 38.5  degrees C. Results indicate that AST
      supplementation had detrimental effects on sperm viability (live spermatozoa) and
      mitochondrial membrane potential when it was added after thawing (P <  0.05) The
      AST supplementation after thawing, however, had a protective effect on plasma
      membrane lipid disorganization (P <  0.05). The percentage of motile spermatozoa
      was not modified by AST supplementation. Nonetheless, after 30 min post-thawing,
      STR and LIN variables (related to straightness of the movement) as well as the
      percentage of rapid lineal spermatozoa were increased with both AST
      supplementation protocols. The GSK3alpha phosphorylation was not modified through
      the incubation time in boar thawed sperm. In summary, results do not support the
      idea of adding AST to the cryopreservation/thawing medium to improve boar sperm
      quality after cryopreservation.

PMID- 30097320
TI  - [Persistent septic portal vein thrombosis in a nonagenarian patient].

PMID- 30097319
TI  - [Evaluation of an educational intervention and a structured review of
      polypharmacy in elderly patients in Primary Care].
AB  - BACKGROUND AND OBJECTIVE: Several interventions have been shown to reduce
      polypharmacy and potentially inappropriate prescription (PIP). The objective of
      the study was to evaluate the number of drugs and PIP before and after an
      educational intervention with the Primary Care physician (PCP), with electronic
      identification of PIP and structured medication review, in elderly patients with
      excessive polypharmacy (>=10 drugs). MATERIAL AND METHODS: A before-after
      intervention study was conducted in the Gipuzkoa district of Osakidetza (Basque
      Country Health System), in a random sample of patients older than 80 years taking
      >= 10 drugs, and whose PCP attended training sessions. Primary outcomes: change
      in the number of drugs and PIP, registered in computerised health records.
      SECONDARY OUTCOMES: benefit/risk ratio assessed by the PCP, safety problems, and
      therapeutic decision. RESULTS: Of the 591 eligible patients, 88 were excluded
      (41: PCP did not attend training sessions, 47: death/transfer/admission),
      including a total of 503 patients with mean age of 84.9 years, with 67.7% women.
      The mean number of drugs and PIP per patient decreased significantly, -0.88 (95%
      CI: -1.04 to -0.72) and -0.19 (95% CI: -0.29 to -0.09), respectively (p<.0001),
      with a 25.8% reduction in the number of patients with excessive polypharmacy.
      SECONDARY OUTCOMES: data collection sheets of 365 patients and 4,168
      prescriptions were collected. The benefit-risk ratio was favourable for 75% of
      the prescriptions, with the most frequent decision being to maintain them (83%).
      Among the 911 prescriptions with an unfavourable/uncertain benefit/risk ratio,
      47.3% were maintained. CONCLUSIONS: The intervention is associated with a
      reduction in excessive polypharmacy and PPI under real-world conditions.

PMID- 30097321
TI  - Are suicide attempters more impulsive than suicide ideators?
AB  - OBJECTIVE: For over 100 years impulsiveness has been cited as a key factor in why
      some people that think about killing themselves go on to attempt suicide. Yet
      prior studies are limited by not using experimental groups that can test this
      hypothesis and by treating impulsiveness as a unidimensional construct. To
      overcome these limitations, we compared suicide ideators and suicide attempters
      on several dimensions of impulsiveness. METHOD: In Study 1 we compared inpatient
      suicide attempters who made an attempt within the prior two weeks (n = 30),
      current inpatient suicide ideators (n = 31), and community controls (n = 34) on
      several dimensions of impulsiveness using self-report and behavioral measures. In
      Study 2 (n = 346), we compared three similar groups based on lifetime and past
      year suicidal behaviors on several of the measures in Study 1. RESULTS: In Study
      1, we found only that negative urgency was clearly elevated among attempters
      compared with ideators. In Study 2, there were no significant differences on any
      impulsiveness constructs, including negative urgency. CONCLUSIONS: Results from
      the two studies suggest that attempters may not have significantly elevated trait
      impulsiveness, compared to ideators; however, attempters may have higher
      impulsiveness when in a negative state.

PMID- 30097322
TI  - Tertiary education regarding stillbirth for student midwives: The tears 4 SMS
      project.
AB  - PROBLEM: Undergraduate education for midwives in the area of stillbirth may be
      lacking. BACKGROUND: When a baby dies the families are usually cared for, at some
      stage in their pregnancy or birth journey, by midwives, however, midwives may not
      be adequately prepared to care for them. AIM: The aim of this study was to
      investigate the current content of stillbirth education in undergraduate
      midwifery curricula in Australia. METHODS: Nineteen midwifery program leaders
      from each of the Australian Universities that deliver undergraduate midwifery
      education were invited to respond to an online survey regarding content related
      to stillbirth risk, prevention and/or bereavement care. There were 10 complete
      surveys. Quantitative survey data were analysed and described using percentages,
      and data from the free text comments collected verbatim. FINDINGS: Responses
      indicated that there is a diverse inclusion of material relating to the topic of
      stillbirth, with different approaches to teaching the content and the amount of
      time devoted to the topic is relatively small. DISCUSSION: This small study in
      scoping curricula from participating Australian Universities indicated that more
      could be done to strengthen stillbirth related content. Stillbirth is a complex
      issue and therefore it is important for midwives to understand not only
      bereavement care but also the physiological underpinnings of issues that could be
      an antecedent cause or precursor for stillbirth. CONCLUSION: There is room to
      improve and standardise appropriate stillbirth curriculum nationally. It is
      imperative that midwives are able to provide sensitive and knowledgeable care to
      all women and their families.

PMID- 30097324
TI  - Widening the perspective on HIV among Indigenous Australians.

PMID- 30097323
TI  - HIV incidence in Indigenous and non-Indigenous populations in Australia: a
      population-level observational study.
AB  - BACKGROUND: Australia has set a national target of ending HIV by 2020, achieving
      this will require the inclusion of priority populations (eg, Indigenous
      Australians) in strategies to reach elimination. To assist in evaluating the
      target of elimination, we analysed HIV notification data for Indigenous and non
      Indigenous Australians. METHODS: Using the National HIV Registry at The Kirby
      Institute at UNSW, Sydney, NSW, Australia, we collated and analysed annual HIV
      notification data for 1996-2015. Patients who were not born in Australia were
      excluded. We calculated the rates of HIV diagnoses with annual trends in
      notification rates for Indigenous versus non-Indigenous Australians by
      demographic characteristics, exposure categories, and stage of HIV at diagnosis.
      For missing data, assumptions were made and verified through sensitivity
      analyses. Annual rate ratio (RR) and 4 year summary rate ratio (SRR) trends were
      calculated to determine patterns of HIV diagnosis in the two populations.
      FINDINGS: Between Jan 1, 1996, and Dec 31, 2015, 11 492 people born in Australia
      were reported with a diagnosis of HIV, of whom 461 (4%) were recorded as
      Indigenous Australians and we classified the remaining 11 031 (96%) as non
      Indigenous Australians. For exposure to HIV, among Indigenous Australians a
      higher proportion of diagnoses occurred among women, and through injecting drug
      use and heterosexual sex than among non-Indigenous Australians (p<0.0001). Among
      Indigenous Australians, we found a significantly higher SRR of HIV diagnoses
      among men in the period 2012-15 than in previous periods (SRR 1.53, 95% CI 1.28
      1.83; p<0.0001), and significantly higher diagnosis among Indigenous women (4.92,
      4.02-6.02; p<0.0001) for the entire study period than among non-Indigenous women.
      Concurrently, a decrease in HIV diagnoses of 1% per annum (RR 0.99, 95% CI 0.98
      0.99; p<0.0001) across the study period was seen among non-Indigenous people.
      Indigenous Australians were more likely to be diagnosed at an advanced stage of
      HIV infection than non-Indigenous Australians (20.8% vs 15.1%; p=0.0088).
      INTERPRETATION: Greater efforts should be made to include Indigenous people in
      prevention strategies, particularly newer biomedical interventions, such as scale
      up of pre-exposure prophylaxis and treatment as prevention initiatives in
      Australia. More involvement of Indigenous Australians in these approaches is also
      required to prevent widening of the gap in HIV diagnosis rates between non
      Indigenous and Indigenous Australians. FUNDING: None.

PMID- 30097325
TI  - Serum Trace Elements in Children with End-Stage Renal Disease.
AB  - OBJECTIVES: Trace elements, which have a crucial role in metabolism and enzymatic
      pathways, are not routinely monitored in the blood of pediatric patients with
      chronic kidney disease. The present study was carried out to determine the serum
      levels of copper (Cu), zinc (Zn), selenium (Se), and lead (Pb) in children with
      ESRD who were currently receiving conservative management or were on long-term
      hemodialysis or continuous ambulatory peritoneal dialysis. METHODS: This study
      involved 200 children who met the inclusion criteria. The children were divided
      into 4 groups: a hemodialysis group, a peritoneal dialysis group, a group of
      children with ESRD treated with conservative management, and a control group.
      Serum levels of Zn, Cu, Se, and Pb were evaluated using an atomic absorption
      spectrophotometer and compared between the groups. RESULTS: There was no
      significant difference in the serum concentration of Cu among the 4 study groups.
      There was also no significant difference in the serum concentrations of Zn, Se,
      and Pb between healthy children and children with CKD treated with conservative
      management or between the hemodialysis and peritoneal dialysis groups. The levels
      of Zn and Se were significantly lower in the hemodialysis and peritoneal dialysis
      groups than in the healthy children or in children with CKD treated with
      conservative management. The level of Pb in the blood was significantly lower in
      healthy children and children with CKD treated with conservative management than
      in the hemodialysis or peritoneal dialysis groups. CONCLUSIONS: The levels of
      trace elements were substantially different between the dialysis groups and
      healthy children and children with CKD treated with conservative management.
      These results highlighted the role of osmosis during dialysis, as dialysate
      impurities can cause a disturbance in the levels of trace elements and the role
      of the kidney, even with minimum residual function, in the homeostasis of trace
      elements.

PMID- 30097326
TI  - Association of Circulatory Iron Deficiency With an Enlarged Heart in Patients
      With End-Stage Kidney Disease.
AB  - OBJECTIVES: High prevalence of iron deficiency (ID) and cardiomyopathy have been
      observed in patients with end-stage kidney disease (ESKD). Our objective was to
      clarify associations between ID and cardiac remodeling in patients with ESKD.
      DESIGN AND METHODS: A cross-sectional study was conducted using 1974 Japanese
      patients with ESKD at the initiation of maintenance dialysis. Levels of
      hemoglobin (Hb), iron status, and cardiac enlargement as assessed by the
      cardiothoracic ratio (CTR) were determined immediately before the first
      hemodialysis session. Circulatory ID was defined as transferrin saturation (TSAT)
      < 20%, and stored ID was defined as ferritin level <100 ng/dL. RESULTS: The mean
      age was 67 years. Median CTR was 54.0%. The prevalence of circulatory and stored
      ID was found to be 38% and 34%, respectively. CTR was higher in patients with
      circulatory ID than in those without. Even in ESKD patients without
      overhydration, significant negative association was observed between TSAT and
      CTR. Higher odds ratios in parallel with higher CTR categories compared with the
      reference category of CTR <45% were found in patients with TSAT <20% on
      multinomial analysis, but ferritin did not show any significant associations. The
      odds ratio for CTR >54% showed an upward trend in patients with TSAT <20% (odds
      ratio: 1.3) and <10% (odds ratio: 1.6) compared with the reference, even after
      adjusting for confounding variables such as Hb and ferritin. However, that
      phenomenon was eliminated by adding usage of an iron agent. CONCLUSIONS:
      Circulatory ID is closely associated with an enlarged heart independent of
      ferritin and Hb. Iron supplementation in the predialysis phase of chronic kidney
      disease may prevent cardiac remodeling independent of Hb level in patients
      chronic kidney disease.

PMID- 30097327
TI  - Reply to: "Mortality due to immunotherapy related hepatitis".

PMID- 30097328
TI  - Corrigendum to "Recipient characteristics and morbidity and mortality after liver
      transplantation" [J hepatol 69 (2018) 43-50].

PMID- 30097329
TI  - Corrigendum to "Single cell sequencing reveals heterogeneity within ovarian
      cancer epithelium and cancer associated stromal cells" [Gyncol. Oncol. 144 (2017)
      598-606].

PMID- 30097330
TI  - Temporomandibular and Odontological Abnormalities in Patients with Rheumatoid
      Arthritis.
AB  - OBJECTIVE: To characterize the orofacial abnormalities in patients with
      rheumatoid arthritis (RA) and compare them with those in a reference population.
      METHODS: The study included 30 RA patients and 30 consecutive patients in an
      odontology clinic in whom RA was ruled out. Patients underwent a clinical dental
      examination which included: 1) clinical and radiographic abnormalities of the
      temporomandibular joint; 2) biomechanical craniocervical analysis; 3) state of
      dentition and treatment needs; 4) periodontal status; 5) oral hygiene status; and
      6) facial pain, which was compared among study groups. In addition, the
      association between the variables studied was determined through correlation
      tests. RESULTS: Patients with RA showed a higher prevalence of temporomandibular
      abnormalities, both clinical (100.0% vs. 60.0%, P<.001) and radiographic,
      including erosions (50.0% vs. 16.0%, P=.010), compared with individuals in the
      control group. Likewise, patients with RA had a greater number of missing teeth
      (6.9+/-5.7 vs. 3.0+/-2.0, P=.001), more caries (13.4+/-5.4 vs. 4.9+/-6.5,
      P=.001), periodontitis (1.3+/-0.9 vs. 0.8+/-0.8, P=.015), poorer oral hygiene
      (43.3% vs. 13.3%, P=.005) and greater facial pain (66.7% vs. 20.0%, P <.001). The
      cephalometric analysis of Rocabado showed differences in the craniocervical angle
      and hyoid triangle between RA and controls. Significant correlations were
      obtained between oral and temporomandibular abnormalities. CONCLUSIONS: Patients
      with RA showed a greater orofacial deterioration, which reflects the importance
      of multidisciplinary care, including periodic dental examination.

PMID- 30097331
TI  - Discrepancies in maternal reports of infant sleep vs. actigraphy by mode of
      feeding.
AB  - OBJECTIVES: Many studies of infant sleep rely solely on parentally-reported data,
      assuming that parents accurately report their infant's sleep parameters. The
      objective of this paper is to examine whether night-time sleep parameters of
      exclusively breastfed or exclusively formula-fed infants differ, and whether
      correspondence between parental reports and objective measures varies by feeding
      type. METHODS: Mother-infant dyads intending to breastfeed or formula-feed
      exclusively for 18 weeks were recruited. Mothers were multiparas and primiparas,
      aged between 18 and 45 years. Infants were full-term, normal birthweight
      singletons. Maternal report and actigraphic data on infant sleep were collected
      fortnightly, from four to 18 weeks postpartum. Data were analysed cross
      sectionally using t-tests and GLM analysis to control for interaction between
      feed-type and sleep location. RESULTS: Actigraphy-assessed infant sleep
      parameters did not vary by feed-type but parentally reported sleep parameters
      did. Maternal report and actigraphy data diverged at 10 weeks postpartum and
      discrepancies were associated with infant feeding type. Compared to actigraphy,
      maternal reports by formula-feeding mothers (controlling for infant sleep
      location) over-estimated infant's Total Sleep Time (TST) at 10 weeks and Longest
      Sleep Period (LSP) at 10, 12 and 18 weeks. CONCLUSIONS: These results raise
      questions about the outcomes of previous infant sleep studies where accuracy of
      parentally-reported infant sleep data is assumed. That parental reports of infant
      sleep vary by feeding type is particularly important for reconsidering previous
      studies of infant sleep development and intervention studies designed to
      influence sleep outcomes, especially where feed-type was heterogeneous, but was
      not considered as an independent variable.

PMID- 30097332
TI  - Corrigendum to "Media consumption and sleep quality in early childhood: results
      from the Ulm SPATZ Health Study" [Sleep Medicine 45 (2018) 7-10].

PMID- 30097333
TI  - Effects of zolpidem/triazolam on cognitive performance 12 hours after acute
      administration.
AB  - OBJECTIVE: Most previous studies have concluded that decreased cognitive function
      and performance due to ultra-short acting hypnotics do not persist after 6-9 h
      post-administration. This study examined the effects of ultra-short acting
      hypnotics on cognitive function and performance 12 h after administration, ie, a
      time considered sufficient for the effects of hypnotics to disappear. METHODS:
      Thirteen healthy young male volunteers (mean age, 23.4 +/- 3.2 years)
      participated in this study. Participants attended three sessions of
      polysomnography (PSG) recording preceded by oral administration of placebo for
      the first session, and 5 mg zolpidem or 0.25 mg triazolam for the second and
      third sessions, in a double-blinded, randomized manner at intervals of at least
      five days. A cognitive test battery was administered following each session,
      consisting of a psychomotor vigilance task (PVT), which reflects alertness and
      sleepiness, digit symbol substitution test (DSST), which reflects attention and
      working memory function, and assessment of subjective sleepiness and mental
      condition using a visual analog scale (VAS). RESULTS AND CONCLUSIONS: The
      administration of hypnotics significantly increased total sleep time, sleep
      efficiency, and sleep stages 2 and 4, and significantly decreased wake after
      sleep onset and sleep stage 1. PVT parameters were not affected by the
      administration of hypnotics, but DSST score was significantly lower, and
      "subjective alertness," "vigor," and "sadness" significantly deteriorated, after
      administration. In conclusion, while objective sleepiness disappeared 12 h after
      the administration of ultra-short acting hypnotics, their effects to decrease
      cognitive function persisted even after 12 h post-administration.

PMID- 30097334
TI  - ECG derived ventricular gradient exceeds echocardiography in the early detection
      of pulmonary hypertension in scleroderma patients.
AB  - BACKGROUND: Patients with systemic sclerosis (SSc) are at risk for developing
      pulmonary hypertension (PH) which is a major cause of death in this population.
      Echocardiographic (TTE) derived pulmonary arterial pressure (PAP) can be
      unreliable for the early detection of PH. Previous studies demonstrate that the
      ECG derived ventricular gradient optimized for right ventricular pressure
      overload (VG-RVPO) can detect PH in a heterogeneous population suspected of PH.
      The aim of this study is to assess the use of the VG-RVPO as a screening and
      monitoring instrument of early PH in SSc patients. METHODS: Serial ECGs and TTEs
      from twenty-seven SSc patients who underwent right heart catheterization (RHC)
      were retrospectively analyzed. The changes in PAP and VG-RVPO over time were
      studied in patients with and without diagnosed PH. RESULTS: Twenty-four patients
      (52.5% female, mean age 58.4 years SD 14.3) were studied. In eleven patients PH
      was confirmed with RHC. In these patients VG-RVPO was significantly higher -8 +/-
      19 than in patients without PH -23 +/- 10 mV.ms, (P < 0.05). In addition, in PH
      patients the VG-RVPO increased over time in contrast to patients without PH (P <
      0.01). The VG was more sensitive to detect disease progression in earlier stages
      of disease as compared to echocardiographic derived PAP. CONCLUSIONS: The VG-RVPO
      is a sensitive, non-invasive and cost effective tool for early detection of PH in
      SSc patients. Serial measurements indicate that the VG-RVPO can be used as a
      follow-up instrument and outperforms TTE to detect early changes in right
      ventricular pressure over time.

PMID- 30097335
TI  - Association of body mass index and diastolic function in metabolically healthy
      obese with preserved ejection fraction.
AB  - BACKGROUND: Small scale cohorts demonstrated an association between body mass
      index (BMI) and diastolic function in a metabolically healthy population. We
      aimed to characterize the relation between BMI and diastolic function in a
      relatively large cohort of metabolically healthy obese with preserved ejection
      fraction. METHODS AND RESULTS: Echocardiograms of metabolically healthy patients
      between 2011 and 2016, who had no significant valvulopathies or atrial
      fibrillation, and had preserved ejection fraction, were retrospectively
      identified and analyzed. Metabolically healthy was defined as lack of known
      diabetes mellitus, hypertension, and hyperlipidemia. Patients were categorized
      into 4 groups according to BMI - normal BMI 18.5-25, overweight 25.01-30, obese
      30.01-35, morbidly obese >35 kg/m2. The cohort consisted of 7057 individuals,
      54.9% males, with a mean age 54 years. Patients in higher BMI groups more
      commonly demonstrated abnormalities in most echocardiographic parameters
      associated with diastolic dysfunction, including left atrial volume index>34
      ml/m2, E/e'>14, e' lateral<10 cm/s, e' septal<7 cm/s, tricuspid regurgitation
      velocity>2.8 m/s and systolic pulmonary artery pressure>=36 mmHg (p<0.01 for all
      comparisons). Morbidly obese carried the highest risk compared to those with
      normal BMI. There were no significant differences between the groups in rates of
      readmission due to heart failure. CONCLUSION: High BMI is associated with
      increased risk of diastolic dysfunction even in metabolically healthy patients.
      Additional trials are needed in order to evaluate whether these echocardiographic
      findings translate into clinical implications.

PMID- 30097336
TI  - Reply to "PCSK9: Entering a new era of cardiovascular risk prediction".

PMID- 30097337
TI  - Circulating long noncoding RNA DKFZP434I0714 predicts adverse cardiovascular
      outcomes in patients with end-stage renal disease.
AB  - BACKGROUND: Cardiovascular (CV) diseases are major causes of mortality in uremic
      patients. Conventional risk factors fail to identify uremic patients with
      increased propensity for adverse CV outcomes. We aimed to test the hypothesis
      that circulating long noncoding RNAs (lncRNAs) could be a prognostic marker to
      predict adverse CV outcomes in uremic patients. METHODS AND RESULTS: Plasma
      lncRNAs were profiled in patients with end-stage renal disease (ESRD, n = 28) or
      chronic kidney disease (CKD, n = 8) and in healthy (n = 12) subjects by RNA
      sequencing. A total of 179 lncRNAs were significantly dysregulated with ESRD; the
      expression signature of plasma lncRNAs distinguished ESRD from both CKD and
      control samples. Analysis on a microarray dataset obtained from renal biopsy
      samples of patients with advanced kidney disease (GSE66494) revealed that a
      significant proportion of plasma lncRNAs (30.7%) and mRNAs (49.5%) dysregulated
      with uremia were similarly dysregulated in diseased kidneys, suggesting that
      plasma RNA profiles mirror the transcriptomal changes in diseased kidney tissues.
      Further analyses identified eight plasma lncRNAs as potential predictors of
      adverse CV outcomes in uremic patients. Validation study in an independent cohort
      of ESRD patients (n = 111) confirmed that elevated plasma lncRNA DKFZP434I0714 is
      a significant independent predictor of adverse CV outcomes in uremic patients.
      Additional experiments demonstrated the functional involvement of DKFZP434I0714
      in the pathogenesis of endothelial dysfunction. CONCLUSIONS: In summary, plasma
      lncRNA expression signature reflects the disease states of uremia. Elevated
      plasma levels of lncRNA DKFZP434I0714 in uremic patients portend a worse CV
      outcome and warrant closer monitoring and more aggressive management.

PMID- 30097338
TI  - Statin therapy contributes to plaque-stability by increasing the presence of
      calcification of plaque.

PMID- 30097339
TI  - Comparative effectiveness of add-on therapy with newer-generation antiepileptic
      drugs in Bulgarian patients with refractory epilepsy.
AB  - OBJECTIVES: The objective of this study is to perform an open, prospective study
      on various aspects of comparative effectiveness of newer-generation antiepileptic
      drugs as add-on therapy in Bulgarian patients with drug-resistant epilepsy.
      METHODS: The study was performed with the participation of 1259 patients with
      epilepsy who attended the Clinic of Neurology at the University Hospital in
      Plovdiv, Bulgaria for regular visits and completed diaries about seizure
      frequency, severity, and adverse events. RESULTS: Oxcarbazepine was used in 82
      patients, topiramate in 120 patients, lamotrigine in 73 patients, levetiracetam
      in 135 patients, pregabalin in 47 patients, tiagabine in 43 patients, gabapentin
      in 18 patients, lacosamide in 12 patients, and retigabine in 6 patients. During
      the first 24 months of study, improvement of seizure severity and frequency was
      most frequent in patients on treatment with pregabalin and levetiracetam and
      rarest in those on treatment with oxcarbazepine. The retention rate of patients
      on pregabalin and tiagabine was significantly lower compared to the retention
      rate of patients on most of the other antiepileptic drugs. The frequency of
      adverse events was higher in patients on treatment with tiagabine and pregabalin.
      CONCLUSION: Despite some similar characteristics of newer-generation
      antiepileptic drugs' effectiveness, levetiracetam stands out with better dynamic
      improvement of seizure severity and frequency and satisfactory tolerability;
      typical for pregabalin is a very good dynamic improvement of seizure severity and
      frequency mainly in patients with focal seizures, but a lower tolerability, and
      the main advantage of oxcarbazepine is a good tolerability, efficacy, however, is
      less satisfactory.

PMID- 30097340
TI  - The impact of sleep characteristics and epilepsy variables on memory performance
      in patients with focal seizures.
AB  - Disturbed sleep can negatively affect overnight memory retention as well as new
      learning the subsequent day. In healthy participants, positive associations
      between memory performance and sleep characteristics (e.g., time spent in slow
      wave sleep [SWS]) have been detected. In a previous study, we found that SWS was
      much reduced in patients with focal seizures, but when correlations between
      memory complaints and various sleep characteristics were considered, the only
      significant relationship was with the time to onset of rapid eye movement (REM)
      sleep (i.e., REM latency). In this study, we investigated the relationships
      between sleep, epilepsy, and objective memory performance variables. Twenty-five
      patients with focal seizures had their memory tested while undergoing a two-day
      ambulatory electroencephalography (EEG). The sleep variables of interest were the
      percentage of time spent in SWS (%SWS) and REM latency. Epilepsy variables
      included the presence of (1) seizures, (2) interictal epileptiform discharges,
      and/or (3) hippocampal lesions as well as site of seizure origin (temporal vs
      extratemporal). Overnight retention (of autobiographical events, a story, and a
      complex geometric figure) and the ability to learn a word list on day 2 were the
      measures of memory. A significant positive correlation was found between word
      list learning and %SWS during the previous night. A significant negative
      correlation was observed between REM latency and overnight retention of
      autobiographical events. Overnight retention scores for the story and geometric
      figure were not related to sleep characteristics but were negatively affected by
      the presence of epileptiform activity. Story retention was also worse for
      temporal lobe epilepsy (TLE) than for patients with extratemporal epilepsy (ETE).
      Those with hippocampal lesions were more impaired than those without lesions on
      word-list learning, autobiographical events' retention, and story retention. When
      multiple contributing factors were entered into regression analyses, %SWS was
      found to be the best predictor of subsequent word-list learning, whereas the
      presence of a hippocampal lesion was the best predictor of overnight retention of
      autobiographical events and a story. These findings provide further evidence of
      the ways in which particular sleep characteristics are associated with memory and
      suggest that treatment of sleep disturbances in patients with epilepsy might be
      helpful for improving their performance.

PMID- 30097341
TI  - A strategy for absolute quantitation of isomers using high performance liquid
      chromatography-ion mobility mass spectrometry and material balance principle.
AB  - Accurate characterization of isomers is a quite challenge and time-consuming
      work. A major bottleneck is the lack of relevant reference standards. In this
      work, we conducted a proof-of-concept study to develop a standard-free method for
      absolute quantitation of isomers by using high performance liquid chromatography
      ion mobility mass spectrometry and material balance principle. The isomer
      structures were characterized by matching the rank order of experimental
      collision cross sections (CCSs) to that of theoretical CCSs. Then a time
      dependent hydrolysis protocol derived from material balance equation was used for
      the calculation of the relative correction factor (F). Finally, the multi-level
      normalized matrix approach was developed to absolutely and precisely quantitate
      isomeric compounds. To assess this method, quercetin-liver microsome reaction
      pool was applied. With the developed method, four isomeric metabolites of
      quercetin were accurately analyzed, and metabolic profiling of quercetin isomeric
      metabolites was firstly reported with the absolute quantitation results. This is
      an accurate yet simple method for the absolute quantitation of positional isomers
      of interest.

PMID- 30097342
TI  - Review on biomimetic affinity chromatography with short peptide ligands and its
      application to protein purification.
AB  - Biomimetic affinity chromatography with short peptide ligands, as a promising
      bioseparation technique, has great potential to protein separation and
      purification, which is based on highly specific biological interactions between
      specially-designed ligands and target proteins. Generally, short peptide ligands
      with the chain length ranging from two to nine amino acids could be divided into
      two types, linear peptide ligands and cyclic peptide ligands. To obtain the
      desired short peptide ligands, rational design strategies could be applied by
      knowing the 3-dimensional (3D) information of the receptors or just knowing the
      surface cavities and the active site of the receptors. Subsequently, several
      technologies could be used to screen the optimal peptide ligands from the
      designed peptide ligands, such as combinatorial chemistry, phage display, mRNA
      display and computer-based screening technology. The screening efficiency is
      dependent on the different technology for individual target proteins. After
      screening, the chromatographic resin could be prepared by coupling the optimal
      short peptide ligand onto a matrix with some spacer arms. The suitable matrix and
      spacer arms are also important to enhance the ability of the peptide ligand for
      protein purification. With the advantages of high affinity, high adsorption
      capacity, structural stability, low immunogenicity and low cost, biomimetic
      affinity chromatography with short peptides as the functional ligands have shown
      an extensive development and application potentiality to protein purification. In
      this review, we focused on the strategies of rational designs and screening for
      short peptide ligands, and some items on the perpetration of new resins and their
      applications for protein purification would also be discussed.

PMID- 30097343
TI  - Stereoselectiveseparation of racemic trans-paroxol, N-methylparoxetine and
      paroxetine containing two chiral carbon centres by countercurrent chromatography.
AB  - Racemic trans-paroxol, trans-N-methylparoxetine and trans-paroxetine containing
      two chiral centres were stereoselectively separated using countercurrent
      chromatography with hydroxypropyl-beta-cyclodextrin as the chiral selector. A two
      phase solvent system composed of n-butyl acetate and 0.1 mol L-1 sodium carbonate
      sodium bicarbonate buffer at pH 9.2 (1:1, v/v) was selected, and 0.10 mol L-1
      hydroxypropyl-beta-cyclodextrin was added to the aqueous phase as the chiral
      selector. Racemic trans-N-methylparoxetine and racemic trans-paroxol (20 mg of
      each) were stereoselectively separated by countercurrent chromatography in an
      individual run, yielding 7.1-8.3 mg of enantiomers with a purity of 95-98%, where
      the recovery of each separated isomer reached approximately 70-83%. Racemic trans
      paroxetine (20 mg) was stereoselectively separated by countercurrent
      chromatography using a recycling elution mode with a biphasic solvent system
      composed of n-hexane: n-butyl acetate: 0.1 mol L-1 sodium carbonate-sodium
      bicarbonate buffer at pH 9.2 (9:1:10, v/v/v), and 0.10 mol L-1 hydroxypropyl-beta
      cyclodextrin was added to the aqueous phase as the chiral selector, yielding 5.0
      5.6 mg of enantiomer with a high purity of over 98-99%.

PMID- 30097344
TI  - The effect of ACL deficiency on the end-to-end distances of the tibiofemoral ACL
      attachment during in vivo dynamic activity.
AB  - PURPOSE: To evaluate the effect of ACL deficiency on the in vivo changes in end
      to-end distances and to determine appropriate graft fixation angles for commonly
      used tunnel positions in contemporary ACL reconstruction techniques. METHODS:
      Twenty-one patients with unilateral ACL-deficient and intact contralateral knees
      were included. Each knee was studied using a combined magnetic resonance and dual
      fluoroscopic imaging technique while the patients performed a dynamic step-up
      motion (~50 degrees  of flexion to extension). The end-to-end distances of the
      centers of the anatomic anteromedial (AM), posterolateral (PL) and single-bundle
      ACL reconstruction (SB-anatomic) tunnel positions were simulated and analyzed.
      Comparisons were made between the elongation patterns between the intact and ACL
      deficient knees. Additionally, a maximum graft length change of 6% was used to
      calculate the deepest flexion fixation angle. RESULTS: ACL-deficient knees had
      significantly longer graft lengths when compared with the intact knees for all
      studied tunnel positions (p < 0.01). The end-to-end distances for the AM, PL and
      SB-anatomic grafts were significantly longer between 0-30 degrees  of flexion
      when compared with the intact knee by p < 0.05 for all. Six percent length change
      occurred with fixation of the AM bundle at 30 degrees  of flexion, PL bundle at
      10 degrees  and the SB-anatomic graft at 20 degrees . CONCLUSIONS: ACL-deficient
      knees had significantly longer in vivo end-to-end distances between 0 degrees -30
      degrees  of flexion for grafts at the AM, PL and SB-anatomic tunnel positions
      when compared with the intact knees. Graft fixation angles of <30 degrees  for
      the AM, <10 degrees  for the PL, and <20 degrees  for the SB-anatomic grafts may
      prevent permanent graft stretch.

PMID- 30097345
TI  - Renal failure parathyroidectomy - Is pre-operative imaging worthwhile?
AB  - BACKGROUND: Tertiary hyperparathyroidism is a significant issue in renal failure
      patients and some require surgery to control their serum calcium. A number of
      imaging techniques are used to localise the position of the parathyroid glands
      prior to surgery. Currently, a combination of ultrasound and isotope preoperative
      localisation imaging is accepted as useful in parathyroid surgery for primary
      disease. However, the use of pre-operative imaging in parathyroid surgery in
      renal failure patients is uncertain. The role of pre-operative imaging of the
      parathyroid glands in patients with renal failure hyperparathyroidism was
      assessed with imaging outcomes compared to operative and pathological findings in
      two cohorts of patients undergoing parathyroid surgery - primary and tertiary.
      METHODS: All data were collected prospectively over a 10-year period (2003-2013)
      from the practice of a single surgeon. Patients were grouped into either primary
      hyperparathyroidism (49 patients) or tertiary hyperparathyroidism (41 patients).
      The majority, 63 of 90 (70%) patients, underwent both ultrasound (US) and isotope
      (MIBI) pre-operative imaging. Pre-operative imaging was correlated with operative
      and pathological findings. FINDINGS: Comparison of the results of the two groups
      using ordinal regression analysis confirmed these imaging techniques are
      significantly more accurate in primary than tertiary parathyroid surgery (p =
      0.022). CONCLUSIONS: While accepted practice of pre-operative combined USS and
      MIBI imaging is essential in unilateral imaged-focused neck exploration for
      primary disease, these imaging techniques have a more limited use pre-operatively
      in renal failure parathyroidectomy.

PMID- 30097346
TI  - Demonstrating the value of musculoskeletal physiotherapy approaches in practice.

PMID- 30097347
TI  - Evaluation of a Pediatric Resident Skills-Based Screening, Brief Intervention and
      Referral to Treatment (SBIRT) Curriculum for Substance Use.
AB  - PURPOSE: To evaluate a screening, brief intervention and referral to treatment
      curriculum for alcohol and other substance use developed, implemented and
      integrated into a pediatric residency program. METHODS: During a 1-month
      adolescent medicine rotation, pediatric, and medicine/pediatric residents in an
      urban teaching hospital completed a 2 1/2-hour formal curriculum including a
      didactic lecture, a 40-minute video describing the Brief Negotiation Interview
      (BNI), and a skill-based session practicing the BNI and receiving individualized
      feedback. Access to a website with didactic material was provided. Outcome
      measures were pre- and post-training knowledge, BNI performance measured with a
      standardized patient using a validated BNI adherence scale, satisfaction with
      training, and adoption of BNI into clinical practice. RESULTS: Of the 106
      residents trained, 92(87%) completed both pre- and post-test evaluations.
      Significant improvements were found in pre- versus post-test scores of knowledge,
      (20.0 [2.4 SD] vs. 24.1 [3.5 SD], p <.001) and BNI performance comparing pre- and
      post BNI adherence scale total scores, (5.14 [1.8 S.D.] vs. 11.5 [.96], p<.001).
      Residents reported high satisfaction with training, [1.4, SD .5, immediately and
      1.6, SD .6, 30-days post training)with scores ranging from 1 to 5 with lower
      score=greater satisfaction. During the 12-month follow-up period, we received 83
      responses from residents reporting a total of 129 BNIs in actual clinical
      settings. CONCLUSIONS: A screening, brief intervention and referral to treatment
      curriculum was successfully integrated into an adolescent medicine elective in a
      pediatric residency program. Residents demonstrated significant improvements in
      knowledge and skills performing the BNI, with high satisfaction and adoption of
      the BNI into clinical practice.

PMID- 30097348
TI  - Detection of Anaplasma phagocytophilum, Candidatus Neoehrlichia sp., Coxiella
      burnetii and Rickettsia spp. in questing ticks from a recreational park,
      Portugal.
AB  - Tick-borne agents with medical relevance have been recorded in Portugal but
      little is known about their occurrence in urban outdoor leisure areas. This study
      aimed to investigate ticks and tick-borne agents in three public parks of
      Lisbon's metropolitan area. A total of 234 questing ticks belonging to eight
      species were found in Parque Florestal de Monsanto (PFM). Ixodes ventalloi
      represented 40% of collections. Mitochondrial genes confirmed Ixodes
      morphological identification, evidencing the intraspecific variability of I.
      ricinus and particularly I. frontalis populations. Regarding tick-borne agents,
      Rickettsia massiliae DNA were found in 21 (9.0%) ticks, Coxiella burnetii in 15
      (6.4%), Anaplasma phagocytophilum in five (2.1%), an agent closely related to
      Candidatus Neoehrlichia mikurensis in two (0.9%), Rickettsia sibirica
      mongolitimonae and Rickettsia monacensis each in one (0.4%). Active enzootic
      cycles were suggested for these agents by the detection of positives in different
      time periods. Five tick species were founded with C. burnetii, including I.
      ventalloi which seems to be a new association record. This tick was also the only
      species found positive for A. phagocytophilum and the Candidatus Neoehrlichia
      mikurensis-like agent. Two A. phagocytophilum variants were detected in PFM, one
      of them representing a potentially new ecotype already found in I. ventalloi from
      another Portuguese area. To the authors' knowledge, this is also the first report
      of such a Candidatus Neoehrlichia mikurensis-like microorganism. These data show
      an interesting diversity of ticks and tick-borne agents with potential public
      health relevance in PFM, an urban recreational area commonly frequented by humans
      and their pets.

PMID- 30097349
TI  - Orthopedic In-Training Examination: An Analysis of the Sports Medicine Section-An
      Update.
AB  - OBJECTIVE: Previously published studies have evaluated Orthopedic In-Training
      Examination sports medicine questions, but none have evaluated whether question
      difficulty has changed over time. DESIGN: Sports medicine subsection questions
      between 2012 and 2016 were evaluated and compared with previously published data
      on Orthopedic In-Training Examination from 2004 to 2009. Question categories were
      classified into 1 of 3 taxonomy levels-basic recall, diagnosis, and advanced
      problem solving. SETTING: Medical University of South Carolina; Charleston, SC,
      29425; Institution. PARTICIPANTS: Two residents evaluated the Sports Subsection
      questions separately. Then an attending physician evaluated the questions to
      resolve discrepancies. A statistician was used for analysis. RESULTS: Utilization
      of imaging modalities averaged 37%, with 28% (11/39) of the questions containing
      2 or more imaging modalities. There were increases in utilization of advanced
      problem-solving questions (45% vs. 27%, p = 0.002) and decreases in basic recall
      questions (49% vs. 67%, p = 0.008) compared with previously published data.
      CONCLUSIONS: While the percentage of the Orthopedic In-Training Examination
      represented by sports medicine has remained relatively unchanged, there were
      fewer questions requiring residents to demonstrate simple recall and diagnosis,
      and increased demand to perform advanced problem solving while utilizing multiple
      imaging modalities.

PMID- 30097350
TI  - Value of Dedicated Research Time for IMGs in Obtaining Surgical Residency
      Training Positions: A 10-Year Review of Applicants from a Medical College in
      Pakistan.
AB  - OBJECTIVE: International Medical Graduates (IMGs) secured greater than 10% of all
      general surgery (GS) residency positions in the US during the past decade. The
      Match process remains competitive, with a significant number of IMGs performing
      dedicated research before residency application. The impact of such research
      remains largely unknown. We aimed to provide an objective analysis of the impact
      of dedicated research time on obtaining a categorical GS residency position.
      DESIGN: Data for National Resident Matching Program Match results from 2008-2017
      was compiled from annual Match lists of the Aga Khan University, Medical College
      (Karachi, Pakistan). Medical graduates provided this information voluntarily each
      year. Data was exported to Microsoft Excel and used for descriptive and
      statistical analysis using SPSS. Candidates were divided into quasi-experimental
      groups based on their preference for direct application (no-research group, n =
      64) or research prior to Match (research group, n = 20). RESULTS: A total of 84
      IMG applicants matched into GS residency positions in the US within the past
      decade. Amongst these, 18 matched directly into categorical positions while 66
      applicants secured preliminary spots. A total of 37 (56%) preliminary candidates
      eventually secured categorical GS residency positions. Research group applicants
      had an overall 85% (n = 17) success rate of obtaining a categorical position,
      while no-research group had a 59% (n = 39) success rate (chi-square test, p =
      0.04). Success rate was 69% (n = 38) for male applicants and 57% (n = 17) for
      female applicants. Median time to a categorical position was 4 years (2-6) for
      the research group and 3 years (1-6) for the no-research group. CONCLUSIONS: Our
      quasi-experimental study demonstrated a higher success rate for Aga Khan
      University, Medical College applicants with significant research background in
      the US, compared to those who did not. Better social integration, enhanced
      mentorship available during research, overcoming of cultural and linguistic
      barriers and a perception as better qualified candidate can be some factors
      contributing to higher success rates.

PMID- 30097351
TI  - Measuring Competence in Surgical Training through Assessment of Surgical
      Entrustable Professional Activities.
AB  - OBJECTIVE: To assess competency in surgical residents with bundled assessments
      using a surgical entrustable professional activity (SEPA) framework. DESIGN: A
      pilot study was conducted using a combination of validated assessment tools
      (multiple choice exam (MCE) questions from the Surgical Council on Resident
      Education [SCORE], the Clinical Assessment and Management Examination -
      Outpatient (CAMEO) form, the Virtual Surgical Patient (VSP) website, and a
      procedure-specific Operative Performance Rating System [OPRS]) to determine
      competency in surgical residents in the treatment of breast cancer and
      gallbladder disease, respectively. SETTING: A large academic institution with a
      surgical training program in the Mid West of the United States. PARTICIPANTS: A
      total of 10 categorical surgical residents were invited to participate. Five
      completed the breast surgical EPA (SEPA) and 5 different residents completed the
      gallbladder SEPA. RESULTS: In terms of performance on the assessments, for the
      breast SEPA, scores did not appear to be related to PGY level, and residents'
      performance in general was the least strong on the MCE and the VSP case. The
      gallbladder SEPA showed a more expected pattern, distinguishing between junior
      and senior residents. As expected, all junior residents were required to
      remediate the OPRS assessment, while the senior residents passed. For the OPRS,
      senior level residents consistently were rated as "excellent" in terms of
      operative flow (5/5), while junior residents were all given a score of "good"
      (3/5). CONCLUSIONS: Assessing competence among surgical residents has been a
      discussion for several years. Varying methods of assessing competence have been
      proposed, but surgical competence is presently defined in a very general way
      through both the ACGME and American Board of Surgery (ABS). Using a SEPA format,
      as proposed, we could ensure specific understanding of each graduating resident's
      ability. These results show that the SEPA may be a valid tool for defining and
      capturing multiple areas of competence that are associated with different disease
      processes.

PMID- 30097352
TI  - Propensity score-matching analyses on the effectiveness of integrated prospective
      payment program for patients with prolonged mechanical ventilation.
AB  - OBJECTIVES: An integrated delivery system with a prospective payment program
      (IPP) for prolonged mechanical ventilation (PMV) was launched by Taiwan's
      National Health Insurance (NHI) due to the costly and limited ICU resources. This
      study aimed to analyze the effectiveness of IPP and evaluate the factors
      associated with successful weaning and survival among patients with PMV. METHODS:
      Taiwan's NHI Research Database was searched to obtain the data of patients aged
      >=17 years who had PMV from 2006 to 2010 (N=50,570). A 1:1 propensity score
      matching approach was used to compare patients with and without IPP (N=30,576).
      Cox proportional hazards modeling was used to examine the factors related to
      successful weaning and survival. RESULTS: The related factors of lower weaning
      rate in IPP participants (hazard ratio [HR]=0.84), were older age, higher income,
      catastrophic illness (HR=0.87), and higher comorbidity. The effectiveness of IPP
      intervention for the PMV patients showed longer days of hospitalization, longer
      ventilation days, higher survival rate, and higher medical costs (in respiratory
      care center, respiratory care ward). The 6-month mortality rate was lower (34.0%
      vs. 32.9%). The death risk of IPP patients compared to those non-IPP patients was
      lower (HR=0.91, P<0.001). CONCLUSIONS: The policy of IPP for PMV patients showed
      higher survival rate although it was costly and related to lower weaning rate.

PMID- 30097354
TI  - Comments on methodological and reporting quality in laboratory studies of human
      eating behaviour.

PMID- 30097355
TI  - Expression of concern-Effect of a high-fat Mediterranean diet on bodyweight and
      waist circumference: a prespecified secondary outcomes analysis of the PREDIMED
      randomised controlled trial.

PMID- 30097353
TI  - What are the motivating and hindering factors for health professionals to
      undertake new roles in hospitals? A study among physicians, nurses and managers
      looking at breast cancer and acute myocardial infarction care in nine countries.
AB  - BACKGROUND: Many European countries experience health workforce skill-mix changes
      due to population ageing, multimorbidity and medical technology. Yet, there is
      limited cross-country research in hospitals. METHODS: Cross-sectional,
      observational study on staff role changes and contributing factors in nine
      European countries. Survey of physicians, nurses and managers (n = 1524) in 112
      hospitals treating patients with breast cancer or acute myocardial infarction.
      Group differences were analysed across country clusters (skill-mix reform
      countries [England, Scotland and the Netherlands] versus no reform countries
      [Czech Republic, Germany, Italy, Norway, Poland and Turkey]) and stratified by
      physicians, nurses and managers, using Chi-squared, Mann-Whitney U and Kruskal
      Wallis tests. RESULTS: Nurses in countries with major skill-mix reforms reported
      more frequently being motivated to undertake a new role (66.5%) and having the
      opportunity to do so (52.4%), compared to nurses in countries with no reforms
      (39.2%; 24.8%; p < .001 each). Physicians and nurses considered intrinsic
      motivating factors (personal satisfaction, use of qualifications) more motivating
      than extrinsic factors (salary, career opportunities). Reported barriers were
      workforce shortages, facilitators were professional and management support.
      Managers' recruitment decisions on choice of staff were mainly influenced by
      skills, competences and experience of staff. CONCLUSION: Managers need to know
      the motivational factors of their employees and enabling versus hindering factors
      within their organisations to govern change effectively.

PMID- 30097357
TI  - Study Protocol of the NVALT25-ELDAPT Trial: Selecting the Optimal Treatment for
      Older Patients With Stage III Non-small-cell Lung Cancer.
AB  - BACKGROUND: Patients aged 75 years or older with stage III non-small-cell lung
      cancer (NSCLC) are underrepresented in clinical trials, leading to a lack of
      evidence for selection of the optimal treatment strategy. Information on benefits
      and harms of concurrent chemoradiotherapy among medically fit elderly patients is
      largely unknown, and reliable tools are needed to distinguish fit from frail
      patients for treatment selection. Also, information regarding quality of life
      during and after treatment is scarce. PATIENTS AND METHODS: This multicenter
      NVALT25-ELDAPT (Dutch Association of Chest Physicians Trial Number 25 - Elderly
      with locally advanced Lung cancer: Deciding through geriatric Assessment on the
      oPtimal Treatment strategy) trial (NCT02284308) consists of a phase III
      randomized trial in combination with an observational study for all patients who
      do not participate in the randomized trial. The first aim of this study is to
      develop a reliable and clinically applicable screening tool to distinguish
      medically fit from frail patients. All patients >= 75 years diagnosed with stage
      III NSCLC are invited to undergo extensive geriatric assessment (part I). The
      second aim is to compare treatment tolerance, survival, and quality of life
      between concurrent and sequential chemoradiotherapy in fit patients (randomized
      trial, part II). For all patients, overall survival adjusted for quality of life
      (quality-adjusted survival) is described for each category of fitness and
      treatment strategy during and after treatment. CONCLUSION: With the results of
      the NVALT25-ELDAPT trial, treatment selection can be optimized and the best
      possible outcomes for each individual older patient with stage III NSCLC can be
      achieved.

PMID- 30097356
TI  - Landscape Plant Selection Criteria for the Allergic Patient.
AB  - Patients with pollen-related allergies are concerned about the species within
      their landscape that provoke their symptoms. Allergists are often asked for
      guidance but few information sources are available to aid patients in the
      recognition of allergenic plants and strategies to avoid personal exposure to
      them. Landscaping and horticultural workers also have few reliable guidance
      references, and what is available usually extols the virtues of the plants rather
      than their negative features. The aim of this article was to provide the results
      of the Landscape Allergen Working Group that was formed by the AAAAI Aerobiology
      Committee, which aimed to fill these existing knowledge gaps and develop guidance
      on producing a low-allergenic landscape. Within the context that complete pollen
      avoidance is unrealistic, the workgroup introduces selection criteria, avoidance
      strategies, and guidance on low-allergenic plants that could be selected by
      patients to reduce the overall pollen burden in their landscape environment.
      Specific focus is placed on entomophilous plants, which require insects as
      dispersal vectors and generally produce lower quantities of pollen, compared with
      anemophilous (wind-pollinated) species. Other biological hazards that can be
      encountered while performing landscaping activities are additionally reviewed and
      avoidance methods presented with the aim of protecting gardeners, and workers in
      the landscape and horticulture industries. The guidance presented in this article
      will ultimately be a helpful resource for the allergist and assist in engaging
      patients who are seeking to reduce the burden of allergen in their landscape
      environment.

PMID- 30097358
TI  - Enhanced Rhodococcus pyridinivorans HR-1 anode performance by adding trehalose
      lipid in microbial fuel cell.
AB  - In this study, a trehalose lipid was added to a Rhodococcus pyridinivorans
      inoculated MFC to improve the power output by enhancing electron transfer. Upon
      trehalose lipid additions of different concentrate from 0 to 20 mg/L, the maximum
      power density increased from 54.7 mW/m2 to 324.4 mW/m2 (5.93 times) while the
      corresponding current density was 3.66 times increased from 0.35 A/m2 to 1.28
      A/m2. Cyclic voltammetry analysis revealed that the addition of trehalose lipid
      increased the electron transfer performance, while electrochemical impedance
      spectroscopy results proved a decrease in internal resistance. It was
      demonstrated that adding bio-surfactant in MFC was a novel way to enhance power
      output performance.

PMID- 30097360
TI  - Risankizumab for psoriasis.

PMID- 30097361
TI  - A novel synthesis of 2-arylbenzimidazoles in molecular sieves-MeOH system and
      their antitubercular activity.
AB  - Arylbenzimidazoles have been synthesized as antimycobacterial agents. An
      efficient synthesis has been developed for 2-arylbenzimidazoles from o
      phenylenediamines and aromatic aldehydes in molecular sieves-methanol system. The
      methodology is straightforward to get 2-arylbenzimidazoles (3a-3z) in excellent
      yields with high chemoselectivity over 2-aryl-1-benzylbenzimidazoles (4a-4z). All
      these benzimidazole analogues were evaluated against M. tuberculosis in BACTEC
      radiometric assay. The compounds 4y and 4z exhibited potential antitubercular
      activity against M. tuberculosis H37RV, MIC at 16 uM and 24 uM respectively. The
      best compound of the series i.e. compound 4y was well tolerated by Swiss-albino
      mice in acute oral toxicity. Compound 4y possessing a diarylbenzimidazole core,
      can further be optimized for better activity.

PMID- 30097359
TI  - Efficacy and safety of risankizumab in moderate-to-severe plaque psoriasis
      (UltIMMa-1 and UltIMMa-2): results from two double-blind, randomised, placebo
      controlled and ustekinumab-controlled phase 3 trials.
AB  - BACKGROUND: Risankizumab is a humanised IgG1 monoclonal antibody that binds to
      the p19 subunit of interleukin-23, inhibiting this key cytokine and its role in
      psoriatic inflammation. We aimed to assess the efficacy and safety of
      risankizumab compared with placebo or ustekinumab in patients with moderate-to
      severe chronic plaque psoriasis. METHODS: UltIMMa-1 and UltIMMa-2 were replicate
      phase 3, randomised, double-blind, placebo-controlled and active comparator
      controlled trials done at 139 sites in Australia, Austria, Belgium, Canada, Czech
      Republic, France, Germany, Japan, Mexico, Poland, Portugal, South Korea, Spain,
      and the USA. Eligible patients were 18 years or older, with moderate-to-severe
      chronic plaque psoriasis. In each study, patients were stratified by weight and
      previous exposure to tumour necrosis factor inhibitor and randomly assigned
      (3:1:1) by use of interactive response technology to receive 150 mg risankizumab,
      45 mg or 90 mg ustekinumab (weight-based per label), or placebo. Following the 16
      week double-blind treatment period (part A), patients initially assigned to
      placebo switched to 150 mg risankizumab at week 16; other patients continued
      their originally randomised treatment (part B, double-blind, weeks 16-52). Study
      drug was administered subcutaneously at weeks 0 and 4 during part A and at weeks
      16, 28, and 40 during part B. Co-primary endpoints were proportions of patients
      achieving a 90% improvement in the Psoriasis Area Severity Index (PASI 90) and a
      static Physician's Global Assessment (sPGA) score of 0 or 1 at week 16 (non
      responder imputation). All efficacy analyses were done in the intention-to-treat
      population. These trials are registered with ClinicalTrials.gov, numbers
      NCT02684370 (UltIMMa-1) and NCT02684357 (UltIMMa-2), and have been completed.
      FINDINGS: Between Feb 24, 2016, and Aug 31, 2016, 506 patients in UltIMMa-1 were
      randomly assigned to receive 150 mg risankizumab (n=304), 45 mg or 90 mg
      ustekinumab (n=100), or placebo (n=102). Between March 1, 2016, and Aug 30, 2016,
      491 patients in UltIMMa-2 were randomly assigned to receive 150 mg risankizumab
      (n=294), 45 mg or 90 mg ustekinumab (n=99), or placebo (n=98). Co-primary
      endpoints were met for both studies. At week 16 of UltIMMa-1, PASI 90 was
      achieved by 229 (75.3%) patients receiving risankizumab versus five (4.9%)
      receiving placebo (placebo-adjusted difference 70.3% [95% CI 64.0-76.7]) and 42
      (42.0%) receiving ustekinumab (ustekinumab-adjusted difference 33.5% [22.7-44.3];
      p<0.0001 vs placebo and ustekinumab). At week 16 of UltIMMa-2, PASI 90 was
      achieved by 220 (74.8%) patients receiving risankizumab versus two (2.0%)
      receiving placebo (placebo-adjusted difference 72.5% [95% CI 66.8-78.2]) and 47
      (47.5%) receiving ustekinumab (ustekinumab-adjusted difference 27.6% [16.7-38.5];
      p<0.0001 vs placebo and ustekinumab). In UltIMMa-1, sPGA 0 or 1 at week 16 was
      achieved by 267 (87.8%) patients receiving risankizumab versus eight (7.8%)
      receiving placebo (placebo-adjusted difference 79.9% [95% CI 73.5-86.3]) and 63
      (63.0%) receiving ustekinumab (ustekinumab-adjusted difference 25.1% [15.2-35.0];
      p<0.0001 vs placebo and ustekinumab). In UltIMMa-2, 246 (83.7%) patients
      receiving risankizumab versus five (5.1%) receiving placebo (placebo-adjusted
      difference 78.5% [95% CI 72.4-84.5]) and 61 (61.6%) receiving ustekinumab
      achieved sPGA 0 or 1 at week 16 (ustekinumab-adjusted difference 22.3% [12.0
      32.5]; p<0.0001 vs placebo and ustekinumab). The frequency of treatment-emergent
      adverse events in UltIMMa-1 and UltIMMa-2 was similar across risankizumab (part
      A: 151 [49.7%] of 304 and 134 [45.6%] of 294; part B: 182 [61.3%] of 297 and 162
      [55.7%] of 291), placebo (part A: 52 [51.0%] of 102 and 45 [45.9%] of 98),
      ustekinumab (part A: 50 [50.0%] of 100 and 53 [53.5%] of 99; part B: 66 [66.7%]
      of 99 and 70 [74.5%] of 94), and placebo to risankizumab (part B: 65 [67.0%] of
      97 and 61 [64.9%] of 94) treatment groups throughout the study duration.
      INTERPRETATION: Risankizumab showed superior efficacy to both placebo and
      ustekinumab in the treatment of moderate-to-severe plaque psoriasis. Treatment
      emergent adverse event profiles were similar across treatment groups and there
      were no unexpected safety findings. FUNDING: AbbVie and Boehringer Ingelheim.

PMID- 30097362
TI  - Synthesis and properties of 4'-C-aminoalkyl-2'-fluoro-modified RNA oligomers.
AB  - Synthesis and properties of double-stranded RNAs (dsRNAs) and small interfering
      RNAs (siRNAs) containing 4'-C-aminoethyl-2'-deoxy-2'-fluorouridine are described.
      Thermal denaturation studies showed that incorporation of 4'-C-aminoethyl-2'
      fluoro analog improved the thermal stabilities of dsRNAs and siRNAs compared to
      the corresponding 4'-C-aminoethyl-2'-O-methyl analog. siRNA incorporating eight
      4'-aminoethyl-2'-fluoro analogs in the passenger strand showed sufficient RNAi
      activity at 1 nM concentration, which was similar to that of the unmodified
      siRNA. Furthermore, the siRNA containing the 4'-C-aminoethyl-2'-fluoro analog
      exhibited high stability in a buffer containing 20% bovine serum. Forty-eight
      percent of the siRNA remained intact after 48 h of incubation. Thus, modification
      of siRNAs by the 4'-C-aminoethyl-2'-fluoro analog would be useful for the
      development of therapeutic siRNA molecules.

PMID- 30097363
TI  - Prevalence and outcome of malnutrition in pediatric patients with chronic
      diseases: Focus on the settings of care.
AB  - BACKGROUND: Information on disease-related malnutrition and related outcomes in
      pediatric patients with chronic diseases in different settings of care is not
      available. METHODS: Consecutive eligible patients attending the out-patient
      clinic (n = 177) or admitted to the day-hospital clinic (n = 163) or to hospital
      (n = 201) were screened for the presence of malnutrition (BMI and/or
      height/length for age z-scores < -2). We recorded data on emergency care
      admissions to hospital that occurred during the 3 years before screening and
      related total days of stay, as well as data on emergency care admissions to
      hospital occurring within 6 months after screening. RESULTS: Prevalence of
      malnutrition was 2-fold higher (P < 0.001) in in-patients (56.7% [95% CI, 49.6
      63.7]) than in patients assessed at the out-patient (33.3% [95% CI, 26.4-40.8])
      and day-hospital (28.3% [95% CI, 21.5-35.8]) clinics. Estimates were
      heterogeneous across diagnostic groups with higher rates in patients with
      neurologic (61%) and cardiac (56%) diseases. Stunting was more frequent among in
      patients, who also had more evident nutritional derangements. Multivariate
      logistic regression (covariates: age, gender, healthcare setting and disease
      group), showed that malnutrition (OR = 1.86 [95% CI, 1.21-2.88]; P = 0.005) was
      significantly associated with prolonged hospitalization (>=15 days) in the 3
      years before screening. In-patients were also more likely to have been
      hospitalized >=15 days (using out-patients as reference category, OR = 2.24 [95%
      CI, 1.39-3.63], P = 0.001), but we did not find any modifying effect
      (interaction) of the setting of care on the association between malnutrition and
      prolonged hospitalization. DISCUSSION: The rates of malnutrition in children with
      chronic diseases are very high and increase hospital care needs, especially when
      they are admitted to hospital. Nutritional care in this patient population is
      recommended.

PMID- 30097364
TI  - Preoperative administration of Omega-3 fatty acids on postoperative pain and
      acute-phase reactants in patients undergoing Roux-en-Y gastric bypass: A
      randomized clinical trial.
AB  - BACKGROUND: The term "Immunonutrition" (IMN) describes the enteral administration
      of certain substrates with a theoretical immunomodulating function. From all the
      elements conforming these IMN formulas, Omega-3 fatty acids (O3FA) are
      hypothesized to be the most important component for immunomodulation, with
      increased anti-inflammatory and antioxidant effect. PATIENTS AND METHODS: A
      prospective randomized clinical trial of all the patients undergoing laparoscopic
      Roux-en-Y gastric bypass was performed. Patients were randomly assigned into 2
      groups: those patients receiving a preoperative balanced energy high-protein
      formula (Control Group) and those ones who received the same preoperative
      nutritional formula enriched with O3FA (Experimental Group). In both groups,
      there was a restriction to 900 Kcal/day. Nutritional intervention started 10 days
      before surgery and was maintained up to 8 h before the surgical act. Preoperative
      weight loss, postoperative pain, complications and acute phase reactants were
      investigated. RESULTS: 40 patients were included in the study, 20 in each group.
      Preoperative excess weight loss (EWL) with the prescribed treatment was 10.6 +/-
      7.7% in Control Group and 14.1 +/- 5.8% in the Experimental Group (p = 0.024).
      Mean postoperative pain was 25 +/- 9.2 mm in Control group and 10,9 +/- 4,4 mm in
      Experimental Group (p = 0.015). CRP determined 24 h after surgery was
      significantly lower in the Experimental Group than in the Control Group. There
      were not significant differences in complications, mortality or readmission rates
      between groups. CONCLUSIONS: The use of a nutritional supplement enriched with
      O3FA is associated with a greater preoperative weight loss, reduced postoperative
      pain and decreased postoperative levels of C reactive protein.

PMID- 30097366
TI  - Design, synthesis and biological evaluation of a series of novel GPR40 agonists
      containing nitrogen heterocyclic rings.
AB  - A novel series of GPR40 agonists is designed by introducing nitrogen-containing
      heterocyclic ring at the terminal phenyl ring of TAK-875 with the aim of
      decreasing its lipophilicity. Three different beta-substituted phenylpropionic
      acids were investigated as the acidic components. A total of 34 compounds have
      been synthesized, among which, compound 30 exhibited comparable GPR40 agonistic
      activity in vitro with TAK-875 and relatively lower lipophilicity through
      calculation (30, EC50 = 1.2 MUM, cLogP = 1.3; TAK-875: EC50 = 5.1 MUM, cLogP =
      3.4). Moreover, compound 30 was able to enhance the insulin secretion of primary
      islets isolated from normal ICR mice and showed no obvious inhibition against
      cytochromes P450 in vitro. In vivo, compound 30 exhibited efficacy in oral
      glucose tolerance test (oGTT) in normal ICR mice.

PMID- 30097367
TI  - Conversion of carbazole carboxamide based reversible inhibitors of Bruton's
      tyrosine kinase (BTK) into potent, selective irreversible inhibitors in the
      carbazole, tetrahydrocarbazole, and a new 2,3-dimethylindole series.
AB  - Incorporation of a suitably-placed electrophilic group transformed a series of
      reversible BTK inhibitors based on carbazole-1-carboxamide and
      tetrahydrocarbazole-1-carboxamide into potent, irreversible inhibitors. Removal
      of one ring from the core of these compounds provided a potent irreversible
      series of 2,3-dimethylindole-7-carboxamides having excellent potency and improved
      selectivity, with the additional advantages of reduced lipophilicity and
      molecular weight.

PMID- 30097365
TI  - ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Calcium,
      phosphorus and magnesium.

PMID- 30097368
TI  - New beta-lactam - Tetramic acid hybrids show promising antibacterial activities.
AB  - beta-Lactams are the most important class of antibiotics, for which the emergence
      of resistance threatens their utility. As such, we explored the extent to which
      the tetramic acid motif, frequently found in naturally occurring antibiotics, can
      be used to generate novel beta-lactam antibiotics with improved antibacterial
      activity. We synthesized new ampicillin - tetramic acid, cephalosporin - tetramic
      acid, and cephamycin - tetramic acid analogs and evaluated their activities
      against problematic Gram-positive and Gram-negative pathogens. Amongst the
      analogs, a 7-aminocephalosporanic acid analog, 3397, and a 7-amino-3-vinyl
      cephalosporanic acid, 3436, showed potent activities against S. aureus NRS 70
      (MRSA) with MICs of 6.25 MUg/mL and 3.13 MUg/mL respectively. These new analogs
      were >=16-fold more potent than cefaclor and cephalexin. Additionally, a Delta2
      cephamycin - tetramic acid analog 3474 which contained a basic guanidinium
      substituent at the 5-position of the tetramic acid core displayed potent activity
      against several clinical strains of K. pneumoniae and E. coli.

PMID- 30097369
TI  - Design, synthesis, and activity evaluation of novel erythropoietin mimetic
      peptides.
AB  - The approval of the erythropoietin (EPO) mimetic peptide drug peginesatide in
      2012 was a breakthrough for the treatment of secondary anemia. However, due to
      severe allergic reactions, peginesatide was recalled a year later. In this study,
      12 novel peptides were designed and synthesized by substituting specific amino
      acids of the monomeric peptide in peginesatide, with the aim of obtaining new EPO
      mimetic peptides with higher activities and lower side effects than the parent
      compound. Their cell proliferation activities were evaluated, and the structure
      activity relationships were analyzed. Five compounds had equal cell proliferation
      activity to the control peptide. Among them, one compound showed a higher in vivo
      activity than the control peptide, with no obvious side effects.

PMID- 30097370
TI  - Design and synthesis of C10 modified and ring-truncated canthin-6-one analogues
      as effective membrane-active antibacterial agents.
AB  - A series of canthin-6-one analogues were designed and synthesized in order to
      study their antibacterial activity and structure-activity relationships. Compound
      22 showed a broad spectrum of antibacterial activity and exhibited better
      bactericidal effect (8-fold superiority against Staphylococcus aureus and 2-fold
      superiority against Ralstonia solanacearum) than fosfomycin sodium and propineb
      with a minimum inhibitory concentration value of 2 MUg/mL. Moreover, it showed
      low cytotoxicity, stimulation on germination rates and good "drug-like"
      properties. Membrane-active mechanism was further studied by fluorescent
      microscopy, scanning electron microscopy, cytoplasmic beta-galactosidase leakage
      assay and evaluation of the molecular docking. The results showed that 22 may
      exert its bactericidal effect by damaging bacterial cell membranes and
      influencing the membrane formation, both of which could lead to cell death. The
      in vivo antibacterial assay with a protective efficacy of 68% demonstrated the
      potential of C ring-truncated canthin-6-one 22 as a new bactericide.

PMID- 30097373
TI  - The development of diffuse panbronchiolitis during the treatment with long-term,
      low-dose clarithromycin for chronic sinusitis.
AB  - Diffuse panbronchiolitis (DPB) is a progressive inflammatory airway disease
      characterized by a chronic cough, copious sputum expectation, dyspnea, and
      chronic sinusitis. Owing to the long-term treatment of low-dose macrolides, the
      prognosis has been remarkably improved. However, in some cases, patients are
      refractory to macrolides, and the subsequent treatment strategies are
      controversial. We herein present a patient with the onset of DPB during treatment
      with long-term, low-dose clarithromycin (CAM) for chronic sinusitis who was
      successfully treated by switching to long-term treatment with normal-dose CAM. We
      should recognize that DPB may develop in patients with chronic sinusitis despite
      treatment with a long-term, low-dose macrolide. We also propose that increasing
      the dose of macrolide may be a useful strategy for treating refractory patients.

PMID- 30097371
TI  - Design, synthesis and antifungal evaluation of novel pyrazole carboxamides with
      diarylamines scaffold as potent succinate dehydrogenase inhibitors.
AB  - Sixteen novel pyrazole carboxamides with diarylamines scaffold were designed,
      synthesized and characterized in detail via 1H NMR, 13C NMR and ESI-HRMS.
      Preliminary bioassays showed that some of the target compounds exhibited good
      antifungal activity against Rhizoctonia solani, Fusarium oxysporum, Phytophthora
      infestans and Fusarium graminearum. Among them, compound 1c exhibited the highest
      antifungal activities against R. solani in vitro with EC50 value of 0.005 mg/L,
      superior to the commercially available fungicide fluxapyroxad (EC50 = 0.033
      mg/L). And compound 1c (IC50 = 0.034 mg/L) showed higher inhibition abilities
      against succinate dehydrogenase than fluxapyroxad (IC50 = 0.037 mg/L). This study
      suggests that compound 1c could be regarded as a potential succinate
      dehydrogenase inhibitor.

PMID- 30097374
TI  - [Modified technique for permanent bundle of His stimulation and its evaluation
      with "strain rate"].

PMID- 30097375
TI  - How Does European Mistletoe Survive Without Complex I?
AB  - Two independent but complementary studies recently provided the first biochemical
      proof of the complete absence of mitochondrial Complex I in a multicellular
      eukaryote. The mitochondrial electron transport chain (mETC) of the hemiparasitic
      European mistletoe (Viscum album) displays dramatic rearrangements of its
      components, most likely reflecting its parasitic lifestyle.

PMID- 30097376
TI  - Low Phosphate Puts Auxin in the Root Hairs.
AB  - The molecular changes that allow plant roots to response to low phosphate levels
      are poorly understood. A series of three papers investigate this phenomenon and
      reveal which components of the auxin response are key for transmitting the
      phosphate signal into changes in root hair phenotypes.

PMID- 30097377
TI  - Mangiferin inhibits high-fat diet induced vascular injury via regulation of
      PTEN/AKT/eNOS pathway.
AB  - Mangiferin (MAN), a naturally occurring polyphenol commonly found in mango and
      papaya. However, little is known its anti-vascular injury effects and the
      underlying mechanisms. This paper investigated the anti-vascular injury effect of
      MAN and the mechanisms in high-fat diet (HFD)-induced C57BL/6J mice and oxidized
      low-density lipoprotein (ox-LDL) induced human umbilical vein endothelial cells
      (HUVECs). The levels of plasma lipid, inflammatory factors and nitric oxide (NO)
      in mice were evaluated. The expression levels of PI3K, AKT, eNOS, PTEN and their
      phosphorylated proteins were measured by western blots. In addition, the PTEN
      siRNA HUVECs were also used. The result showed that MAN markedly decreased the
      plasma lipid, inflammatory level in HFD-induced vascular injury mice
      respectively. Furthermore, MAN alleviate ox-LDL-stimulated dysfunction of HUVECs,
      restored the diminished NO release, decreased the ROS generation, significantly
      increased the expression of p-Akt, p-eNOS, and decreased the expression of PTEN,
      but have no effect on PI3K. However, the protective effects of MAN were
      significantly reduced by co-treatment with PI3K inhibitor or abolished by eNOS
      inhibitor. In addition, MAN has no protective effect on ox-LDL induced PTEN-siRNA
      HUVECs injury. Collectively, MAN appeared to alleviate ox-LDL-stimulated
      dysfunction of HUVECs via the PTEN/Akt/eNOS signaling pathway, thus decrease
      vascular injury in HFD-administrated mice.

PMID- 30097378
TI  - Assessing the impact of the public nutrition information environment: Adapting
      the cancer information overload scale to measure diet information overload.
AB  - OBJECTIVE: A growing body of research suggests that exposure to too much
      information - particularly contradictory information that characterizes much
      health-related information - can lead to feeling overwhelmed. This construct has
      been conflated with fatalistic beliefs that are negatively associated with
      preventive behaviors. The objective of this study was to adapt the 8-item Cancer
      Information Overload (CIO) scale to assess overload of healthy diet information.
      METHODS: Confirmatory factor analyses with a community sample of rural California
      adults (n = 290; 75% female; 58% Latino; 46% <= H.S./G.E.D.). RESULTS: Items
      assessing Diet Information Overload loaded significantly on their relevant
      factor; factor loadings were acceptable (beta > .40). The adapted original scale
      (CFI = 1.000, RSMEA = .000, SMSR = .022) and a shorter 5-item scale (CFI = .984,
      RMSEA = .051, SMSR = .026) fit well. CONCLUSION: The Cancer Information Overload
      scale was successfully adapted and shortened to measure perceptions - previously
      mischaracterized as fatalistic - pertaining to diet information. Improved
      measures distinguishing between fatalistic beliefs and outcomes of the
      information environment are critical. PRACTICE IMPLICATIONS: Understanding
      information overload is important for shaping prevention messages distinct from
      those needed to address fatalistic beliefs. Nutrition education efforts should
      consider the broader - cluttered - information environment in which nutrition
      education and communication occurs, and public health messages may drown.

PMID- 30097379
TI  - The red thread.

PMID- 30097380
TI  - Missing the forest for the trees.
AB  - Despite my efforts and those of quite a few experienced colleagues we failed to
      diagnose our friend's wife illness and prevent her demise. But a sad and
      frustrating experience also stimulates reflection and dwelling on potential
      errors we made and hope to identify the next time.

PMID- 30097381
TI  - Patterns of family communication and preferred resources for sharing information
      among families with a Lynch syndrome diagnosis.
AB  - OBJECTIVES: To explore patterns of communication among families with a Lynch
      syndrome diagnosis and understand what resources could facilitate family
      communication. METHODS: 127 probands (i.e., first person in family with
      identified mutation) and family members participated in semi-structured
      interviews about: how they learned about the Lynch syndrome diagnosis, with whom
      they shared genetic test results, confidence in sharing results with other family
      members, and helpfulness of educational resources. RESULTS: Both probands and
      family members were most likely to share genetic test results with parents and
      siblings, and least likely to share results with aunts, uncles, and cousins. Most
      participants felt very confident sharing their test results with family members,
      but reported that certain topics such as cancer risk were challenging to convey.
      Probands reported the most helpful resources to be access to a specialty clinic
      or website, while family members described general printed materials as most
      helpful. CONCLUSIONS: Families affected by Lynch syndrome may experience barriers
      to communication with more distant relatives, and may benefit from receiving
      specific resources (e.g., websites about Lynch syndrome, print materials) to
      facilitate family communication. PRACTICE IMPLICATIONS: Providers could emphasize
      the need to share information with more distant family members and provide
      appropriate supportive resources.

PMID- 30097383
TI  - Evaluating the Implementation of Project Re-Engineered Discharge (RED) in Five
      Veterans Health Administration (VHA) Hospitals.
AB  - BACKGROUND: Improving the process of hospital discharge is a critical priority.
      Interventions to improve care transitions have been shown to reduce the rate of
      early unplanned readmissions, and consequently, there is growing interest in
      improving transitions of care between hospital and home through appropriate
      interventions. Project Re-Engineered Discharge (RED) has shown promise in
      strengthening the discharge process. Although studies have analyzed the
      implementation of RED among private-sector hospitals, little is known about how
      hospitals in the Veterans Health Administration (VHA) have implemented RED. The
      RED implementation process was evaluated in five VHA hospitals, and contextual
      factors that may impede or facilitate the undertaking of RED were identified.
      METHODS: A qualitative evaluation of VHA hospitals' implementation of RED was
      conducted through semistructured telephone interviews with personnel involved in
      RED implementation. Qualitative data from these interviews were coded and used to
      compare implementation activities across the five sites. In addition guided by
      the Practical, Robust Implementation and Sustainability Model (PRISM), cross-site
      analyses of the contextual factors were conducted using a consensus process.
      RESULTS: Progress and adherence to the RED toolkit implementation steps and
      intervention components varied across study sites. A majority of contextual
      factors identified were positive influences on sites' implementation. CONCLUSION:
      Although the study sites were able to tailor and implement RED because of its
      adaptability, redesigning discharge processes is a significant undertaking,
      requiring additional support/resources to incorporate into an organization's
      existing practices. Lessons learned from the study should be useful to both VHA
      and private-sector hospitals interested in implementing RED and undertaking a
      care transition intervention.

PMID- 30097382
TI  - First description of a new uncultured purple sulfur bacterium colonizing marine
      mangrove sediment in the Caribbean: Halochromatium-like PSB from Guadeloupe.
AB  - Here, we report the first description of a marine purple sulfur bacterium (PSB)
      from sulfide-rich sediments of a marine mangrove in the Caribbean. TEM shows that
      this new isolate contains intracytoplasmic vesicular membrane systems (containing
      bacteriochlorophyll a) and larger internal sulfur granules, confirmed by EDXS
      analyses performed using ESEM. The sulfur distribution and mapping obtained for
      this PSB strain has allowed us to conclude that elemental sulfur is formed as an
      intermediate oxidation product and stored intracellularly. SEM shows that the
      bacterial cells are ovoid and extremely motile via lophotrichous flagella.
      Phylogenetic characterization, based on the analysis of 16S rDNA and functional
      gene pufM sequences, demonstrate that this strain belongs to the Chromatiaceae
      and may be a representative of a new species of the genus Halochromatium. Thus,
      reduced sediments of marine mangrove represent a sulfide-rich environment that
      sustains the development of Chromatiaceae, in addition to sulfur-oxidizing
      bacteria and cyanobacteria, as previously reported.

PMID- 30097384
TI  - Adaptation and Implementation of a Transitional Care Protocol for Patients
      Undergoing Complex Abdominal Surgery.
AB  - BACKGROUND: Transitional care protocols are effective at reducing readmission for
      medical patients, yet no evidence-based protocols exist for surgical patients. A
      transitional care protocol was adapted to meet the needs of patients discharged
      to home after major abdominal surgery. APPROACH: The Coordinated-Transitional
      Care (C-TraC) protocol, initially designed for medical patients, was used as the
      initial framework for the development of a surgery-specific protocol (sC-TraC).
      Adaptation was accomplished using a modification of the Replicating Effective
      Programs (REP) model, which has four phases: (1) preconditions, (2)
      preimplementation, (3) implementation, and (4) maintenance and evolution. A
      random sample of five patients each month was selected to complete a phone survey
      regarding patient satisfaction. Preimplementation planning allowed for
      integration with current systems, avoided duplication of processes, and defined
      goals for the protocol. The adapted protocol specifically addressed surgical
      issues such as nutrition, fever, ostomy output, dehydration, drain
      character/output, and wound appearance. After protocol launch, the rapid
      iterative adaptation process led to changes in phone call timing, inclusion and
      exclusion criteria, and discharge instructions. OUTCOMES: Survey responders
      reported 100% overall satisfaction with the transitional care program. KEY
      INSIGHTS: The adaptable nature of sC-TraC may allow for low-resource hospitals,
      such as rural or inner-city medical centers, to use the methodology provided in
      this study for implementation of local phone-based transitional care protocols.
      In addition, as the C-TraC program has begun to disseminate nationally across US
      Department of Veterans Affairs (VA) hospitals and rural health settings, sC-TraC
      may be implemented using the existing transitional care infrastructure in place
      at these hospitals.

PMID- 30097385
TI  - Protease Specificity: Towards In Vivo Imaging Applications and Biomarker
      Discovery.
AB  - Proteases are considered of major importance in biomedical research because of
      their crucial roles in health and disease. Their ability to hydrolyze their
      protein and peptide substrates at single or multiple sites, depending on their
      specificity, makes them unique among the enzymes. Understanding protease
      specificity is therefore crucial to understand their biology as well as to
      develop tools and drugs. Recent advancements in the fields of proteomics and
      chemical biology have improved our understanding of protease biology through
      extensive specificity profiling and identification of physiological protease
      substrates. There are growing efforts to transfer this knowledge into clinical
      modalities, but their success is often limited because of overlapping protease
      features, protease redundancy, and chemical tools lacking specificity. Herein, we
      discuss the current trends and challenges in protease research and how to exploit
      the growing information on protease specificities for understanding protease
      biology, as well as for development of selective substrates, cleavable linkers,
      and activity-based probes and for biomarker discovery.

PMID- 30097386
TI  - [Patient involvement in clinical practice guidelines is poor after 12 years of
      German guideline standards: A review of guideline methodologies].
AB  - BACKGROUND: As early as 1997, the German Guideline for Guidelines laid down
      patient participation in guideline development as the cornerstone of good,
      trustworthy medical guidelines. The German Guideline Assessment Tool (DELBI)
      published in 2005 requires patients or relatives to be involved in the
      development of medical guidelines. Ideally, this should be effected through
      membership in the author group. The Association of the Scientific Medical
      Societies in Germany (AWMF) recommends this approach for the so-called S3
      guidelines (systematically developed guidelines) and S2k guidelines (consensus
      based guidelines). The present study addresses the question of whether and to
      what extent German guideline publishers adhere to these principles of patient
      orientation. METHODS: For this purpose, a descriptive analysis of the guidelines
      valid at the beginning of November 2017 was carried out. All guidelines (n=520)
      of the AWMF member societies were assessed. We evaluated S3- and S2k guidelines
      only, as these are of particular importance for patient involvement due to the
      requirement of an interdisciplinary guideline group. Data were reported on the
      involvement of patients (as co-authors of medical guidelines) and on the
      existence of guidance documents addressing patients and the public (so-called
      patient information and patient guidelines). RESULTS: Regarding the 105 (165) S3
      (S2k) guidelines, we found evidence on patient involvement in guideline
      development in 99 (134) cases (94 % of S3 / 81 % of S2k guidelines). In 61 (87)
      guidelines, authors had contributed to the authors group (58 % / 53 %) and 59
      (80) guidelines with voting rights (56 % / 48 %). For 50 (15) S3 (S2k) guidelines
      (48 % / 9 %), the guideline report provided information on the existence or
      planned development of guidance documents for patients and the public (patient
      guidelines or patient information). Guidance-related patient information was
      available on the internet for only 37 (2) S3 (S2k) guidelines (35 % / 2 %).
      CONCLUSION: A substantial gap remains between patient / public involvement
      standards for guideline development and practice in Germany, even 12 years after
      the publication of national guideline standards. This is a missed opportunity
      since guidelines without adequate participation of those affected by the
      recommendations have a problem of legitimacy and transparency. Only guidelines
      where patients were involved in all voting processes during development build and
      strengthen trust between patients and the medical profession. And only those who
      present the rationale for medical recommendations in a generally understandable
      and comprehensible manner let affected individuals make individual decisions.

PMID- 30097388
TI  - Comparison of clinical characteristics of bacteremia from Elizabethkingia
      meningoseptica and other carbapenem-resistant, non-fermenting Gram-negative
      bacilli at a tertiary medical center.
AB  - BACKGROUND: Acquired carbapenem resistance among non-fermenting Gram-negative
      bacilli (NFGNB), such as Pseudomonas aeruginosa and Acinetobacter calcoaceticus
      Acinetobacter baumannii complex (ACB complex), is a serious problem in nosocomial
      infections. We previously reported that patients infected with the intrinsically
      carbapenem-resistant Elizabethkingia meningoseptica were associated with high
      mortality. However, little information is available regarding the clinical
      outcome of E. meningoseptica bacteremia when compared to that of other carbapenem
      resistant NFGNB. METHODS: We conducted an observational study that included
      consecutive patients with E. meningoseptica, carbapenem-resistant ACB complex,
      carbapenem-resistant P. aeruginosa, and Stenotrophomonas maltophilia bacteremia
      at a Taiwanese medical center in 2015. We compared the clinical characteristics
      and outcomes between patients with E. meningoseptica bacteremia and those with
      other carbapenem-resistant NFGNB bacteremia. RESULTS: We identified 30 patients
      with E. meningoseptica, 71 with carbapenem-resistant ACB complex, 25 with S.
      maltophilia, and 17 with carbapenem-resistant P. aeruginosa bacteremia. The
      clinical characteristics, disease severity, and previous antibiotic exposures
      were similar between patients with bacteremia either due to E. meningoseptica or
      other carbapenem-resistant NFGNB. Patients with E. meningoseptica bacteremia had
      a higher rate of appropriate empirical antibiotics than those with other
      carbapenem-resistant NFGNB and was less associated with central venous
      catheterization. The 28-day mortality rates were similar between patients with E.
      meningoseptica and the other carbapenem-resistant NFGNB bacteremia (46.7% vs 46%,
      p = 0.949). CONCLUSION: The mortality rate of E. meningoseptica bacteremia was as
      high as other carbapenem-resistant NFGNB infections. The emerging E.
      meningoseptica infection calls for active surveillance and continued awareness
      from clinical physicians for this serious carbapenem-resistant infection.

PMID- 30097387
TI  - Low cognitive flexibility as a risk for heavy alcohol drinking in non-human
      primates.
AB  - Chronic alcohol abuse is frequently considered a habitual or inflexible behavior;
      however, measures of pre-existing cognitive flexibility prior to initiation of
      alcohol use are usually not available. This study used rhesus monkeys and an
      attentional set-shifting task to investigate whether pre-existing cognitive
      flexibility would predict increased risk for heavy alcohol drinking. As
      previously reported, monkeys were given 30 daily set-shifting sessions prior to
      alcohol access. These sessions consisted of the same sequence of eight unique
      visual discriminations (sets) of two objects that varied on two dimensions
      (shapes and colors). The ratio of errors per trials, session duration, and
      maximum set reached were primary dependent variables from each session and were
      used to compose a session performance index (PI) that ranged from a low
      performance PI of 31 to an optimal performance PI of 247. Here, animals underwent
      an alcohol induction period followed by 22 weeks of daily (22-h) self
      administration sessions with free access to water and alcohol. Based on average
      daily alcohol intake during 22 weeks of 22-h/day access, the monkeys were
      categorized as non-heavy (mean = 2.0 +/- 0.3 g/kg/day; n = 3) and heavy (mean =
      3.3 +/- 0.5 g/kg/day; n = 6) drinkers. The two groups diverged in performance on
      the set-shifting task across the 30 pre-alcohol sessions, and at the end of the
      pre-alcohol testing, the group average PI was 216 +/- 27 and 137 +/- 71 for the
      future non-heavy and heavy drinkers, respectively. The data show that low
      cognitive flexibility assessed with a set-shifting procedure was predictive of
      future classification as a heavy alcohol drinker. The data highlight individual
      differences in both cognitive flexibility and in alcohol self-administration in
      this population of rhesus monkeys.

PMID- 30097389
TI  - Hybrid deep brain stimulation system to manage stimulation-induced side effects
      in essential tremor patients.

PMID- 30097391
TI  - Refining treatment choices for ADHD.

PMID- 30097392
TI  - Exploring the Association of Asthma with Urinary Stone Disease: Results from the
      National Health and Nutrition Examination Survey 2007-2014.
AB  - BACKGROUND: The prevalence of urinary stone disease (USD) and asthma is rising
      and has recently been associated in a pediatric population. OBJECTIVE: To
      investigate the association between asthma and USD in a nationally representative
      adult population. DESIGN, SETTING, AND PARTICIPANTS: We analyzed the National
      Health and Nutrition Examination Survey 2007-2014, a US population-based cross
      sectional study. A history of asthma and USD was obtained by self-report to
      questionnaires. USD severity was represented by graded stratification into non
      stone formers, single stone formers, and recurrent stone formers (>2 stones).
      OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Odds ratios (ORs) for asthma were
      calculated for respondents with USD and separately for the graded USD groups.
      Survey-weighted logistic regression models included adjustments for demographics
      (model A), medical information (model B), and for relevant medications (model C).
      RESULTS AND LIMITATIONS: A total of 20 906 participants aged >=20 yr were
      included in the analysis. Of these, 9.2% reported of having a history of kidney
      stones. Logistic regression analysis adjusted for demographics, medical
      conditions, and medications showed that stone formers had significantly increased
      odds of asthma (odds ratio=1.23; 95% confidence interval: 1.03-1.47; p=0.023).
      Separate logistic regression analysis demonstrated a graded association between
      single and recurrent stone formers and the odds of having asthma (p=0.01), which
      remained significant in the 20-50-yr-old population and the diabetic population,
      especially for recurrent stone formers. Causal relationships were limited by
      cross-sectional nature of the study. CONCLUSIONS: Increasing severity of USD is
      associated with an increase in odds for asthma among American adults, providing
      impetus for future studies into the mechanisms explaining this phenomenon.
      PATIENT SUMMARY: In this report, we looked at self-reported histories of asthma
      and urinary stone disease (USD) using information from a large US population. We
      found that asthma was associated with USD; however, further studies are needed to
      elucidate this relationship.

PMID- 30097393
TI  - Spontaneous Coronary Artery Dissection and Hypothyroidism.
AB  - INTRODUCTION AND OBJECTIVES: Thyroid hormone affects the metabolism of all
      tissues in the body. The aim of this study was to analyze the prevalence and
      implications of thyroid disorders in a cohort of consecutive patients with
      spontaneous coronary artery dissection (SCAD). METHODS: A total of 73 patients
      with SCAD were analyzed. Baseline characteristics and clinical outcomes were
      compared between euthyroid and hypothyroid patients. Subsequently, the prevalence
      of thyroid function abnormalities and the clinical characteristics of SCAD
      patients were compared with those in 73 patients with acute coronary syndrome but
      without SCAD, matched by age, sex, and presentation. RESULTS: Mean age was 55 +/-
      12 years and 26% had hypothyroidism. Compared with patients with normal thyroid
      function, patients with SCAD and hypothyroidism were all women (100% vs 69%, P =
      .01), more frequently had dissection in distal (74% vs 41%, P = .03) and tortuous
      coronary segments (68% vs 41%, p = .03), and more frequently received
      conservative medical management (79% vs 41%, P = .007). During a mean clinical
      follow-up of 4.1 +/- 3.8 years, 23% of the patients had adverse cardiac events
      irrespective of thyroid function status. The prevalence of hypothyroidism was
      higher in patients with SCAD than in matched patients with acute coronary
      syndrome without SCAD (26% vs 8%, P = .004). CONCLUSIONS: There is a high
      prevalence of hypothyroidism in patients with SCAD. Patients with SCAD and
      hypothyroidism are more frequently women, more frequently have distal dissections
      in tortuous vessels, and are more frequently managed with a conservative medical
      strategy.

PMID- 30097390
TI  - Comparative efficacy and tolerability of medications for attention-deficit
      hyperactivity disorder in children, adolescents, and adults: a systematic review
      and network meta-analysis.
AB  - BACKGROUND: The benefits and safety of medications for attention-deficit
      hyperactivity disorder (ADHD) remain controversial, and guidelines are
      inconsistent on which medications are preferred across different age groups. We
      aimed to estimate the comparative efficacy and tolerability of oral medications
      for ADHD in children, adolescents, and adults. METHODS: We did a literature
      search for published and unpublished double-blind randomised controlled trials
      comparing amphetamines (including lisdexamfetamine), atomoxetine, bupropion,
      clonidine, guanfacine, methylphenidate, and modafinil with each other or placebo.
      We systematically contacted study authors and drug manufacturers for additional
      information. Primary outcomes were efficacy (change in severity of ADHD core
      symptoms based on teachers' and clinicians' ratings) and tolerability (proportion
      of patients who dropped out of studies because of side-effects) at timepoints
      closest to 12 weeks, 26 weeks, and 52 weeks. We estimated summary odds ratios
      (ORs) and standardised mean differences (SMDs) using pairwise and network meta
      analysis with random effects. We assessed the risk of bias of individual studies
      with the Cochrane risk of bias tool and confidence of estimates with the Grading
      of Recommendations Assessment, Development, and Evaluation approach for network
      meta-analyses. This study is registered with PROSPERO, number CRD42014008976.
      FINDINGS: 133 double-blind randomised controlled trials (81 in children and
      adolescents, 51 in adults, and one in both) were included. The analysis of
      efficacy closest to 12 weeks was based on 10 068 children and adolescents and
      8131 adults; the analysis of tolerability was based on 11 018 children and
      adolescents and 5362 adults. The confidence of estimates varied from high or
      moderate (for some comparisons) to low or very low (for most indirect
      comparisons). For ADHD core symptoms rated by clinicians in children and
      adolescents closest to 12 weeks, all included drugs were superior to placebo (eg,
      SMD -1.02, 95% CI -1.19 to -0.85 for amphetamines, -0.78, -0.93 to -0.62 for
      methylphenidate, -0.56, -0.66 to -0.45 for atomoxetine). By contrast, for
      available comparisons based on teachers' ratings, only methylphenidate (SMD 
      0.82, 95% CI -1.16 to -0.48) and modafinil (-0.76, -1.15 to -0.37) were more
      efficacious than placebo. In adults (clinicians' ratings), amphetamines (SMD 
      0.79, 95% CI -0.99 to -0.58), methylphenidate (-0.49, -0.64 to -0.35), bupropion
      (-0.46, -0.85 to -0.07), and atomoxetine (-0.45, -0.58 to -0.32), but not
      modafinil (0.16, -0.28 to 0.59), were better than placebo. With respect to
      tolerability, amphetamines were inferior to placebo in both children and
      adolescents (odds ratio [OR] 2.30, 95% CI 1.36-3.89) and adults (3.26, 1.54
      6.92); guanfacine was inferior to placebo in children and adolescents only (2.64,
      1.20-5.81); and atomoxetine (2.33, 1.28-4.25), methylphenidate (2.39, 1.40-4.08),
      and modafinil (4.01, 1.42-11.33) were less well tolerated than placebo in adults
      only. In head-to-head comparisons, only differences in efficacy (clinicians'
      ratings) were found, favouring amphetamines over modafinil, atomoxetine, and
      methylphenidate in both children and adolescents (SMDs -0.46 to -0.24) and adults
      (-0.94 to -0.29). We did not find sufficient data for the 26-week and 52-week
      timepoints. INTERPRETATION: Our findings represent the most comprehensive
      available evidence base to inform patients, families, clinicians, guideline
      developers, and policymakers on the choice of ADHD medications across age groups.
      Taking into account both efficacy and safety, evidence from this meta-analysis
      supports methylphenidate in children and adolescents, and amphetamines in adults,
      as preferred first-choice medications for the short-term treatment of ADHD. New
      research should be funded urgently to assess long-term effects of these drugs.
      FUNDING: Stichting Eunethydis (European Network for Hyperkinetic Disorders), and
      the UK National Institute for Health Research Oxford Health Biomedical Research
      Centre.

PMID- 30097394
TI  - Cancer and Acute Coronary Syndrome. A Close, but Complicated Relationship.
      Response.

PMID- 30097395
TI  - Antithrombotic Therapy and Surgery: From Consensus to Clinical Practice. Response
      to Related Letters.

PMID- 30097396
TI  - Estimation of Lifetime Risk of Cardiovascular Disease (IBERLIFERISK): A New Tool
      for Cardiovascular Disease Prevention in Primary Care.
AB  - INTRODUCTION AND OBJECTIVES: To develop a predictive function of lifetime
      cardiovascular risk, including morbidity and mortality, in a healthy working
      population in Spain. METHODS: Retrospective cohort study. We selected healthy
      workers, aged 18 to 65 years, with no history of cardiovascular disease, who
      underwent a health assessment between 2004 and 2007. We used 70% of the cohort to
      develop the risk equation, and the remaining 30% to validate the equation. Four
      Cox proportional hazards models were constructed using cardiovascular events and
      competing events as dependent variables. The same models were replicated for men
      and women separately. Fatal and nonfatal events were assessed until 2014.
      RESULTS: A total of 762 054 individuals were selected. The mean age was 35.48
      years and 71.14% were men. Significant risk variables in the model included
      manual occupations, being a smoker or exsmoker, diabetes mellitus,
      antihypertensive treatment, systolic blood pressure, total cholesterol, high
      density lipoprotein cholesterol, and lipid-lowering treatment; in men, the model
      also included alcohol consumption, body mass index, a family history of early
      coronary disease in first-degree relatives, renal failure, and diastolic blood
      pressure. The area under the curve receiver operating characteristic was 0.84
      (95%CI, 0.82-0.85) in men and 0.73 (95%CI, 0.66-0.80) in women. Calibration
      showed underestimation in low-risk deciles and overestimation in high-risk
      deciles. CONCLUSIONS: The new lifetime cardiovascular risk model has satisfactory
      discrimination and calibration, with better results in men than in women.

PMID- 30097397
TI  - A simple and novel technique for training in microvascular suturing in a rat
      model.
AB  - BACKGROUND: Though microvascular clamps are widely used for anastomosis training,
      there still have several shortcomings, including the bulging, expensiveness and
      unavailability due to sterilization. The aim of this study is to introduce a
      simple and novel microvascular training model without use of microvascular
      clamps. METHODS: Femoral vessels of Sprague Dawley rats training model were used
      to evaluate the usefulness of 4-0 silk as a slipknot for performing arterio
      arterial and veno-venous microvascular anastomoses. A total of 12 Sprague Dawley
      rats were randomly assigned to either slipknot group or vascular clamp group. We
      also assess other endpoints, including ischemic time, patency rate, and clinical
      features. An additional histological study was performed to compare their
      immediate traumatic effects on vessel wall. RESULTS: There was no ischemic change
      or congestive sign in the lower limb after microvascular anastomosis. The total
      warm ischemic time for the vascular anastomosis was not significantly different.
      We performed the patency test immediately after microvascular anastomosis and one
      week after surgery. No intraoperative vascular bleeding was found during these
      procedures and no thrombosis occurred postoperatively. The histologic damages to
      occluded area were not significantly different in both groups. CONCLUSION: We
      demonstrate a microsurgical suture technique performed without any vascular clamp
      on a rat model. This rat model was designed for training in the technique of
      microvascular anastomosis. Compared with microvascular clamps, silk slipknot is a
      cheap, easily available, less space-occupying technique while performing
      microvascular anastomoses training. This preliminary study provides a simple and
      effective alternative method for microvascular anastomosis training.

PMID- 30097398
TI  - Long-term changes in the metabolic and nutritional parameters after gastrectomy
      in early gastric cancer patients with overweight.
AB  - BACKGROUND: With the increase in the prevalence of overweight, percentage of
      overweight patients with gastric cancer has also increased. This 5-year
      retrospective cohort study was performed to investigate long-term changes in the
      metabolic and nutritional parameters of early gastric cancer (EGC) patients with
      overweight after gastrectomy. METHODS: EGC patients who underwent gastrectomy
      were followed up over a 5-year period. We included 393 patients (261 men, 132
      women) who had an initial body mass index (BMI) of >=23 kg/m2, and analyzed the
      longitudinal changes in the metabolic and nutritional parameters. RESULTS: Body
      weight and random glucose, alanine aminotransferase (ALT), hemoglobin, and serum
      calcium levels significantly decreased, while serum protein and albumin levels
      increased in both men and women after gastrectomy. The odds ratios (ORs) for BMI
      >= 25 kg/m2 (P < 0.001 for men and women), random glucose >= 126 mg/dL (men; P =
      0.001, women; P < 0.001), and ALT > 40 IU/dL (men; P < 0.001, women; P = 0.018)
      were lower in both men and women after 5 years. The ORs for low protein and
      albumin levels decreased, although the ORs for anemia and hypocalcemia increased
      in both sexes at 5 years after gastrectomy. CONCLUSION: Gastrectomy in overweight
      patients followed up over 5-year could lead to approximately 10% weight loss and
      favorable changes in the metabolic parameters in both men and women. The risk of
      anemia and hypocalcemia increased, and the risk of low protein and albumin levels
      decreased in both sexes.

PMID- 30097399
TI  - Auricular reconstruction of congenital microtia by using the modified Nagata
      method: Personal 10-Year experience with 1350 cases.
AB  - BACKGROUND: Total auricular reconstruction is currently one of the most
      challenging plastic surgery procedures. Herein, we present our 10-year experience
      with 1350 cases of ear reconstruction by using Nagata method with necessary
      improvement. METHODS: Factors related to ear reconstruction, namely, remnant ear,
      mastoid skin, adjacent scalp, rib cartilages, normal ear, and mastoid process,
      were carefully evaluated before operation. An individualized design and precise
      framework fabrication were performed for each patient. Necessary modifications in
      fabricating base frame, helix, tragus, and antihelix were introduced to achieve a
      stable and individualized framework. These efforts also reduced the quantity of
      cartilage required for ear reconstruction. RESULTS: Follow-up time ranged from 1
      month to 5 years, and 1217 (90.1%) patients were satisfied with the reconstructed
      ears, which showed appropriate color, texture, size, and location. The
      modifications made conferred a harmonious and individualized contour of the
      reconstructed ears. Incidence of all complications such as hematoma, skin
      necrosis, and framework absorption was very low. CONCLUSIONS: Based on
      preoperative assessment, individualized design, and precise sculpting, a
      harmonious and individual auricle with detailed anatomical structures was
      achieved by using our modified Nagata method in which a stable and sophisticated
      framework can be fabricated with less cartilage requirement.

PMID- 30097400
TI  - High-Resolution Pulse Oximetry (HRPO): A Cost-Effective Tool in Screening for
      Obstructive Sleep Apnea (OSA) in Acute Stroke and Predicting Outcome.
AB  - INTRODUCTION: Obstructive sleep apnea (OSA) is a well-known risk factor for
      stroke. This is attributed to multiple mechanisms such as endothelial
      dysfunction, atrial fibrillation, hypertension, and comorbid obesity. STOP
      questionnaire alone is unreliable to diagnose OSA and in-hospital sleep study is
      costly and can be technically challenging. We used high-resolution pulse oximetry
      (HRPO) to test the feasibility of screening for OSA and predicting outcome.
      METHODS: Data from 115 stroke patients who underwent HRPO was collected including
      Oxygen desaturation index (ODI) <4%, pulse rate, arterial oxygen saturation
      (SaO2), and time spent at SaO2 saturation <88%. We also collected data on various
      confounders. The outcomes measured were NIHSS (National Institutes of Health
      Stroke Scale), mRS (modified Rankin Score) on discharge, and discharge
      disposition. RESULTS: Overall 115 patients with valid HRPO data were included in
      the study. Mean age was 64+/-12years with 68% white, 22% black, and 10% Hispanic
      population. Of this cohort of 115 patients, 56% were males. Of the subjects
      enrolled 22 had atrial fibrillation, 27 had type 2 diabetes, 7 had resistant
      hypertension, and 7 had patient foramen ovale. Of the 115 patients, 75 patients
      were found to have ODI of >10 and the mean ODI was 29+/-30. The NIHSS on
      admission was 6.14+/-6.93 and on discharge was 4.46+/-4.59, mRS on discharge was
      1.70+/-1.67 with 52% being discharged home, 43% to rehab, 2% nursing home, and 3%
      to long-term acute care facility. In this study, we show a strong association
      between atrial fibrillation and increasing ODI (P<.001, OR 1.01, CI 1.00-1.03).
      In addition, our study also shows an association between discharges outcome of
      rehab (more deficits leading to higher disability) versus discharge to home
      (lesser deficits) if ODI was <=10 (P = 0.005, OR 3.76, CI 1.49-9.52).
      CONCLUSIONS: Our study showed that there is a significant burden of OSA in acute
      stroke patients. ODI emerged as a predictor of atrial fibrillation and discharge
      disposition in our study. HRPO may be a cost-effective tool to screen and
      evaluate for OSA in acute stroke patients.

PMID- 30097401
TI  - Identifying Unmet Rehabilitation Needs in Patients After Stroke With a Graphic
      Rehab-CompassTM.
AB  - BACKGROUND: Unmet rehabilitation needs are common among stroke survivors. We
      aimed to evaluate whether a comprehensive graphic "Rehab-Compass," a novel
      combination of structured patient-reported outcome measures, was feasible and
      useful in facilitating a capture of patients' rehabilitation needs in clinical
      practice. METHODS: A new graphic overview of broad unmet rehabilitation needs
      covers deficits in functioning, daily activity, participation, and quality of
      life. It was constructed by using 5 patient-oriented, well-validated, and
      reliable existing instruments with converted data into a 0 (worst outcome) to 100
      (best outcome) scale but unchanged in terms of variable properties. Satisfaction
      of the Rehab-CompassTM was studied by a qualitative interview of 9 patients with
      stroke and 3 clinicians. Practical feasibility and capacity of the instrument
      were evaluated in a cross-sectionalstudy with 48 patients at 5-month follow-ups
      after subarachnoid hemorrhage. RESULTS: The Rehab-CompassTM identified and
      graphically visualized a panoramic view of the multidimensional needs over time
      which was completed before clinical consultation. The Rehab-CompassTM appeared to
      be feasible and time-efficientin clinical use. The interviews of both patients
      and clinicians showed high satisfaction when using the Rehab-CompassTM graph. In
      the studied stroke patients, the Rehab-CompassTM identified memory and processing
      information, fatigue, mood, and pain after subarachnoid hemorrhage as the most
      common problems. CONCLUSIONS: The graphic Rehab-CompassTM seems to be a feasible,
      useful, and time-saving tool for identification of unmet rehabilitation needs
      among stroke survivors in clinical practice. Further research is needed to make
      the Rehab-CompassTM more concise and evaluate the instrument among different
      stroke subgroups.

PMID- 30097403
TI  - Optimization of a dual-functional biocatalytic system for continuous hydrolysis
      of lactose in milk.
AB  - In this study, an amino-functionalized silica matrix encapsulating beta
      galactosidase was first synthesized in situ, with subsequent covalent anchoring
      of lysozyme to the outer part of the amino-grafted matrix. Fourier transform
      infrared (FTIR) spectra verified that beta-galactosidase was successfully
      encapsulated. Meanwhile, the co-immobilized enzymes were demonstrated to retain
      suitable enzymatic activities and outstanding operational stability during
      successive reaction cycles. Furthermore, when used for lactose removal from skim
      milk, the packed-bed column system achieved both a high lactose hydrolysis rate
      and microbial inactivation ratio during 30 days of continuous operation. Notably,
      this system exhibited favorable stability during 60 days of continuous hydrolysis
      of lactose in solution and thus may be appropriate for further development for
      use in industrial lactose removal from milk.

PMID- 30097402
TI  - Integration of Chest CT CAD into the Clinical Workflow and Impact on Radiologist
      Efficiency.
AB  - RATIONALE AND OBJECTIVES: The purpose of this paper is to describe the
      integration of a commercial chest CT computer-aided detection (CAD) system into
      the clinical radiology reporting workflow and perform an initial investigation of
      its impact on radiologist efficiency. It seeks to complement research into CAD
      sensitivity and specificity of stand-alone systems, by focusing on report
      generation time when the CAD is integrated into the clinical workflow. MATERIALS
      AND METHODS: A commercial chest CT CAD software that provides automated detection
      and measurement of lung nodules, ascending and descending aorta, and pleural
      effusion was integrated with a commercial radiology report dictation application.
      The CAD system automatically prepopulated a radiology report template, thus
      offering the potential for increased efficiency. The integrated system was
      evaluated using 40 scans from a publicly available lung nodule database. Each
      scan was read using two methods: (1) without CAD analytics, i.e., manually
      populated report with measurements using electronic calipers, and (2) with CAD
      analytics to prepopulate the report for reader review and editing. Three
      radiologists participated as readers in this study. RESULTS: CAD assistance
      reduced reading times by 7%-44%, relative to the conventional manual method, for
      the three radiologists from opening of the case to signing of the final report.
      CONCLUSION: This study provides an investigation of the impact of CAD and
      measurement on chest CTs within a clinical reporting workflow. Prepopulation of a
      report with automated nodule and aorta measurements yielded substantial time
      savings relative to manual measurement and entry.

PMID- 30097404
TI  - Comparison of biofunctional activity of Asparagus cochinchinensis (Lour.) Merr.
      Extract before and after fermentation with Aspergillus oryzae.
AB  - Asparagus cochinchinensis root (ACR) is used in traditional Chinese medicine. In
      this study, ACR was first extracted with 25% ethyl acetate (EA) and then
      fermented by Aspergillus oryzae to enhance its antioxidant activity and evaluate
      its potential antityrosinase activity. The physiological activity and
      cytotoxicity of A. oryzae-fermented ACR extract, along with its antityrosinase
      activity and effects on melanogenic factor levels in human epidermal melanocytes
      (HEMs), were analyzed and compared with those of the unfermented extract. The
      results showed that the physiological activity of the fermented extract in vitro
      or in cells was significantly higher than that of the unfermented extract. The
      IC50 values for 2,2-diphenyl-1-picrylhydrazine radical scavenging activity,
      reducing power, and antityrosinase activity in vitro for the fermented extract
      were 250.6 +/- 32.5, 25.7 +/- 3.5, and 50.6 +/- 3.1 mg/L, respectively. The
      fermented extract favored cellular antityrosinase activity with low melanin
      production in human melanoma cells compared with the unfermented extract. The
      inhibitory mechanism of melanin synthesis by unfermented extract was independent
      of the tested melanogenesis-related proteins. However, the inhibitory mechanism
      of the fermented extract was possibly caused by synergistic inhibition of these
      proteins. Thus, A. oryzae-fermented ACR extract may be used for developing new
      health food or cosmetic ingredients.

PMID- 30097405
TI  - Implementing an innovated liver ex-situ machine perfusion technology: The 2018
      Joint International Congress of ILTS, ELITA and LICAGE.

PMID- 30097406
TI  - SOHO State of the Art and Next Questions: Management of Myelodysplastic Syndromes
      With Deletion 5q.
AB  - Myelodysplastic syndrome (MDS) with deletion 5q [del(5q)] is a distinct clinical
      and pathologic disease subset that is exquisitely sensitive to lenalidomide for
      the treatment of red blood cell transfusion-dependent anemia. Lenalidomide
      resistance, including primary resistance, occurs by clonal evolution, which is
      frequently attributable to the presence of somatic mutations in the DNA-binding
      domain of the TP53 gene. The treatment options after development of resistance to
      lenalidomide are limited and consist of hypomethylating agents, clinical trials,
      and allogeneic hematopoietic stem cell transplantation. We discuss evidence-based
      strategies to devise a treatment algorithm for patients with MDS with del(5q).

PMID- 30097407
TI  - Autologous dermis-fat grafts in head and neck patients: Indications and
      evaluation in reconstructive surgery.
AB  - PURPOSE: The aim of this study was to examine the indications and results of
      autologous dermis-fat grafts in the reconstruction of maxillofacial soft-tissue
      defects. MATERIALS AND METHODS: A total of 93 patients with dermis-fat graft
      reconstruction due to a soft tissue defect in the head and neck region were
      enrolled in this retrospective clinical study between March 2002 and January
      2017. They were classified into the subgroups 'parotid surgery', 'orbital
      surgery', and 'facial surgery'. All the patients were evaluated for wound
      complications, and the general indications were discussed. RESULTS: In all, 96
      dermis-fat grafts were performed in 93 patients. A total of 34 complications that
      arose in 30 patients were assessed. The dermis-fat graft was primarily
      transplanted in 50 cases and secondarily in 46. Of the patients, 90 showed well
      integrated dermis-fat grafts. A major complication occurred in three patients.
      CONCLUSION: Dermis-fat grafts for the reconstruction of maxillofacial soft-tissue
      defects represent a reliable method with a low rate of major complications. The
      graft can be used as a primary as well as secondary transplant. Especially in
      parotid and orbital surgery, the dermis-fat graft appears to be a transplant of
      choice. It can also be used as an alternative in facial surgery, lip enhancement,
      and special individual cases.

PMID- 30097408
TI  - Three-dimensional facial anatomy evaluation: Reliability of laser scanner
      consecutive scans procedure in comparison with stereophotogrammetry.
AB  - Laser scanner devices are acquiring a growing importance in facial anatomy. Most
      studies have analysed facial scans obtained through two simultaneous captures,
      whereas the same result can be obtained by consecutive three-dimensional (3D)
      scans. However, this latter procedure has not yet been validated. Fourteen
      volunteers underwent face image capture through stereophotogrammetry (VECTRA M3)
      and three consecutive facial scans through a laser scanner (Konica Minolta
      Vi910). The concordance between 14 linear distances, 12 angles, facial surface
      area and volume measurements was verified by the Bland-Altman test and
      calculation of absolute and relative technical errors of measurement (TEM/rTEM).
      The two facial images obtained by the different devices were then registered to
      calculate point-to-point distance. Most of linear distances and angles showed a
      high agreement, with "very good" or "good" rTEMs, ranging between 1.1% and 6.4%.
      Surface area measurements agreed well between the devices (rTEM: 6.3%), while
      volumes were poorly comparable (rTEM: 25.8%); the root mean square point-to-point
      distance was 0.80 mm (SD: 0.41). This study first tested the concordance of
      measurements on facial images obtained by stereophotogrammetry and consecutive
      laser scans. Results highlight the reliability of linear distances, angles and
      surface areas measurements, but discourage volume assessment and registration of
      surfaces acquired through different devices.

PMID- 30097409
TI  - Hydroxyapatite calvaria graft repair in experimental diabetes mellitus in rats.
AB  - Among the systemic conditions that impact negatively on the planning and
      execution of surgical procedures, diabetes mellitus (DM) is the primary clinical
      condition responsible for complications. This study investigated bone formation
      in critical defects surgically filled with hydroxyapatite (HA) in diabetic rats.
      A descriptive, randomized sample and blinded analysis were conducted to test bone
      regeneration in critical bone defects surgically performed in rat calvaria.
      Twenty adult male Wistar rats were randomly divided into two groups: control,
      normoglycemic animals (CG); and test, streptozotocin-induced hyperglycemic
      animals (TG). A circular bone defect was filled with HA and maintained
      subperiosteally. The clinical parameters evaluated were body weight, water and
      food intake, fasting blood glucose, and bone alkaline phosphatase. Bone-grafted
      area samples were submitted for histomorphometric and stereological analysis. The
      TG showed a significantly higher rate of new bone formation compared with the CG,
      sacrificed 15 days after surgery (p < 0.0001). However, at the end of the study,
      there was no significant difference in the amount of bone formed between groups
      (p = 0.077). In parallel, with the increase in osteoblastic activity observed in
      the TG by the measurement of systemic bone alkaline phosphatase (p = 0.016), the
      analysis of polarized microscopy and stereology demonstrated a lower level
      collagen maturation and mineralization in the TG. Quantitatively, the TG showed
      significantly better results for bone gain in the first 15 days. Qualitative
      assessments, however, showed fewer collagen fibers and bone maturation in the TG
      compared with the CG both at 15 and 45 days. Therefore, the postoperative
      evaluation of bone grafts with HA in hyperglycemic situations should consider the
      systemic and local effects of this condition on the quality of bone repair,
      rather than identifying the filling or stability of the grafted area after the
      process. We conclude that clinically detectable bone repair in diabetic animal
      models submitted to hydroxyapatite grafts may be satisfactory in the early
      stages. However, hyperglycemia compromises the quality of the newly formed bone
      and the collagen cross-linking involved in this process.

PMID- 30097410
TI  - Fractures of the mandibular condyle: A comparison of patients, fractures and
      treatment characteristics between Groningen (The Netherlands) and Dresden
      (Germany).
AB  - PURPOSE: To explore differences in patient, fracture, accident and treatment
      characteristics between patients treated for a mandibular condyle fracture in the
      University Centres of Dresden and Groningen, as an explanation for differences
      treatment results. MATERIALS AND METHODS: Patients' fracture, accident and
      treatment characteristics were obtained from the medical records of Dresden and
      Groningen from January 1, 2008, to August 31, 2011, and were analysed using
      logistic regression analysis. RESULTS: In Dresden, compared to Groningen,
      patients were generally older (OR 1.03, 95% CI 1.02; 1.05, per year), were more
      often male (OR 2.54, 95% CI 1.48; 4.34) and more often had intracapsular (OR
      2.95, 95% CI 1.67; 5.22) and low condylar (OR 1.86, 95% CI 1.14; 3.04) fractures.
      In Groningen 98% of patients received closed treatment and in Dresden 42%.
      CONCLUSION: Significant differences in patients and fractures and treatments were
      found between both Centres. These differences can partly be explained by the
      demographics of the cities and differences in imaging techniques (e.g., computed
      tomography, Orthopantomogram, Towne projection) applied to identify fractures.
      This study illustrates that differences in diagnosis, treatment and outcome are
      not only related to the health care system but also to differences in patient
      characteristics between centres.

PMID- 30097411
TI  - Comparison between patient specific implants and conventional mini-plates in Le
      Fort I osteotomy with regard to infections: No differences in up to 3-year follow
      up.
AB  - Individually designed osteotomies and milled or printed patient-specific
      osteosynthesis materials are rapidly becoming a standard in maxillofacial
      reconstructive surgery. The benefits of using patient-specific implants (PSIs) in
      orthognathic surgery are especially clear in complex cases, and for this reason
      they are rapidly becoming common practice. We have earlier reported the benefits
      related to the use of PSIs as reposition and fixation system in Le Fort I
      osteotomy. The aim of this study was to compare complications associated with
      fixation with PSIs (31 patients) versus conventional mini-plates (37 patients) in
      Le Fort I osteotomy. No statistically significant differences in infection,
      reoperations or soft tissue problems were observed between the two systems used.
      Interestingly, three of the 37 patients in the mini-plate group underwent
      reoperation due to insufficient advancement or malocclusion, whereas none of the
      patients in the PSI group needed reoperation. In conclusion, PSIs are reliable
      for use in orthognathic surgery, with no signs of infection associated
      complications.

PMID- 30097412
TI  - Breathing on a hot planet.

PMID- 30097413
TI  - First results from the Swedish National Pancreatic and Periampullary Cancer
      Registry.
AB  - BACKGROUND: Despite improvements in therapy regimens over the past decades,
      overall survival rates for pancreatic and periampullary cancer are poor. Specific
      cancer registries are set up in various nations to regional differences and to
      enable larger prospective trials. The aim of this study was to describe the
      Swedish register, including possibilities to improve diagnostic work-ups,
      treatment, and follow-up by means of the register. METHODS: Since 2010, all
      patients with pancreatic and periampullary cancer (including also patients who
      have undergone pancreatic surgery due to premalignant or benign lesions) have
      been registered in the Swedish National Periampullary and Pancreatic Cancer
      registry. RESULTS: In total 9887 patients are listed in the registry; 8207 of
      those have malignant periampullary cancer. Approximately one-third (3282
      patients) have had resections performed, including benign/premalignant
      resections. 30-day and 90-day mortality after pancreatoduodenectomy is 1.5% and
      3.5%, respectively. The overall 3-year survival for resected pancreatic ductal
      adenocarcinoma is 35%. Regional variations decreased over the studied period, but
      still exist. CONCLUSION: Results from the Swedish National Registry are
      satisfactory and comparable to international standards. Trends over time show
      increasing resection rates and some improved results. Better collaboration and
      openness within pancreatic surgeons is an important side effect.

PMID- 30097414
TI  - Preoperative risk prediction for intraductal papillary mucinous neoplasms by
      quantitative CT image analysis.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are radiographically
      identifiable potential precursor lesions of pancreatic adenocarcinoma. While
      resection is recommended when main duct dilation is present, management of branch
      duct IPMN (BD-IPMN) remains controversial. This study sought to evaluate whether
      preoperative quantitative imaging features of BD-IPMNs could distinguish low-risk
      disease (low- and intermediate-grade dysplasia) from high-risk disease (high
      grade dysplasia and invasive carcinoma). METHODS: Patients who underwent
      resection between 2005 and 2015 with pathologically proven BD-IPMN and a
      preoperative CT scan were included in the study. Quantitative image features were
      extracted using texture analysis and a novel quantitative mural nodularity
      feature developed for the study. Significant features on univariate analysis were
      combined with clinical variables to build a multivariate prediction model.
      RESULTS: Within the study group of 103 patients, 76 (74%) had low-risk disease
      and 27 (26%) had high-risk disease. Quantitative imaging features were prognostic
      of low-vs. high-risk disease. The model based only on clinical variables achieved
      an AUC of 0.67 and 0.79 with the addition of quantitative imaging features.
      CONCLUSION: Quantitative image analysis of BD-IPMNs is a novel method that may
      enable risk stratification. External validation may provide a reliable non
      invasive prognostic tool for clinicians.

PMID- 30097415
TI  - High frequency of Haemophilus influenzae associated with respiratory tract
      infections among Malaysian Hajj pilgrims.
AB  - BACKGROUND: Overcrowding during the annual Hajj pilgrimage has been known to
      increase the risk of infectious diseases transmission. Despite the high
      prevalence of respiratory illness among Malaysian Hajj pilgrims, knowledge about
      the etiologic pathogens is yet very limited. Thus, this study aimed to determine
      the spectrum of bacterial respiratory pathogens among the Hajj pilgrims returning
      to Malaysia in year 2016. METHODS: Expectorated sputum specimens were collected
      from the Hajj pilgrims with symptomatic respiratory tract infections (RTIs).
      Subsequently, the bacterial pathogens were identified using the standard
      bacteriological culture method and Vitek II system. RESULTS: This study indicated
      that 255 (87.33%) out of 292 cultured sputa were positive with at least one
      potential pathogenic bacteria. Out of 345 total bacterial isolates, 60% (n=207)
      were Haemophilus influenzae, which was associated with both single bacterium
      infection (132/173, 76.3%) and multiple bacterial infections (75/82, 91.5%). The
      other bacterial isolates included; Klebsiella pneumoniae (n=37, 10.7%), Moraxella
      catarrhalis (n=27, 7.8%), Haemophilus parainfluenzae (n=25, 7.2%), Streptococcus
      group G (n=18, 5.2%), Klebsiella spesies (n=16, 4.6%), Streptococcus pneumoniae
      (n=11, 3.2%) and few other organisms. CONCLUSION: High frequency of H. influenzae
      was isolated from Malaysian Hajj pilgrims, especially those with respiratory
      symptoms. Further study should evaluate the actual pathogenicity of the organism
      and the interactions between the respiratory microbiota towards developing
      effective prevention strategies of RTIs among the local pilgrims.

PMID- 30097416
TI  - Negative Impact of CMV and BKV Infections on Kidney-Allograft Function at 1-Year
      Post-Transplantation: Can it Be Changed by Modifying Immunosuppression?

PMID- 30097417
TI  - Anterior crossbite treatment in the primary dentition: Three case reports.
AB  - Anterior crossbite is characterized by negative horizontal overjet between the
      jaws, and occurs due to skeletal, functional, and/or dental imbalances. It is
      often found in primary and mixed dentition stages and causes severe aesthetic,
      functional, and psychosocial impairment. We report the facial and occlusal
      effects of maxillary protraction associated with rapid maxillary expansion in
      three young patients with primary dentition. The proposed treatment plan
      consisted of protraction and rapid maxillary expansion. The mechanical device
      chosen was the facial mask combined with a McNamara rapid palatal expander. The
      anterior crossbite was corrected, and significant facial and cephalometric
      benefits were obtained. The treatment of maxillary protraction during the
      deciduous dentition stage, in cases where there is good acceptance and
      collaboration by patients, provides excellent clinical results and constitutes a
      viable treatment option.

PMID- 30097418
TI  - ?

PMID- 30097419
TI  - Differences in the Effect of Internet-Based Cognitive Behavioral Therapy for
      Improving Nonclinical Depressive Symptoms Among Workers by Time Preference:
      Randomized Controlled Trial.
AB  - BACKGROUND: Previous randomized controlled trials (RCTs) have shown a significant
      intervention effect of internet-based computerized cognitive behavioral therapy
      (iCBT) on improving nonclinical depressive symptoms among healthy workers and
      community residents in a primary prevention setting. Time preference is one's
      relative valuation for having a reward (eg, money) at present than at a later
      date. Time preference may affect the effectiveness of cognitive behavioral
      therapy. OBJECTIVE: This RCT aimed to test the difference of intervention effect
      of an iCBT program on improving nonclinical depressive symptoms between two
      subgroups classified post-hoc on the basis of time preference among workers in
      Japan. METHODS: All workers in one corporate group (approximate n=20,000) were
      recruited. Participants who fulfilled the inclusion criteria were randomly
      allocated to either intervention or control groups. Participants in the
      intervention group completed 6 weekly lessons and homework assignments within the
      iCBT program. The Beck Depression Inventory-II (BDI-II) and Kessler's
      Psychological Distress Scale (K6) measures were obtained at baseline and 3-, 6-,
      and 12-month follow-ups. Two subgroups were defined by the median of time
      preference score at baseline. RESULTS: Only few (835/20,000, 4.2%) workers
      completed the baseline survey. Of the 835 participants, 706 who fulfilled the
      inclusion criteria were randomly allocated to the intervention or control group.
      Participants who selected irrational time preference options were excluded (21
      and 18 participants in the intervention and control groups, respectively). A
      three-way interaction (group [intervention/control] * time [baseline/follow-up] *
      time preference [higher/lower]) effect of iCBT was significant for BDI-II
      (t1147.42=2.33, P=.02) and K6 (t1254.04=2.51, P=.01) at the 3-month follow-up,
      with a greater effect of the iCBT in the group with higher time preference. No
      significant three-way interaction was found at the 6- and 12-month follow-ups.
      CONCLUSIONS: The effects of the iCBT were greater for the group with higher time
      preference at the shorter follow-up, but it was leveled off later. Workers with
      higher time preference may change their cognition or behavior more quickly, but
      these changes may not persist. TRIAL REGISTRATION: UMIN Clinical Trials Registry
      UMIN000014146; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?
      recptno=R000016466 (Archived by WebCite at http://www.webcitation.org/70o2rNk2V).

PMID- 30097420
TI  - Internet of Things Buttons for Real-Time Notifications in Hospital Operations:
      Proposal for Hospital Implementation.
AB  - BACKGROUND: Hospital staff frequently performs the same process hundreds to
      thousands of times a day. Customizable Internet of Things buttons are small,
      wirelessly-enabled devices that trigger specific actions with the press of an
      integrated button and have the potential to automate some of these repetitive
      tasks. In addition, IoT buttons generate logs of triggered events that can be
      used for future process improvements. Although Internet of Things buttons have
      seen some success as consumer products, little has been reported on their
      application in hospital systems. OBJECTIVE: We discuss potential hospital
      applications categorized by the intended user group (patient or hospital staff).
      In addition, we examine key technological considerations, including network
      connectivity, security, and button management systems. METHODS: In order to
      meaningfully deploy Internet of Things buttons in a hospital system, we propose
      an implementation framework grounded in the Plan-Do-Study-Act method. RESULTS: We
      plan to deploy Internet of Things buttons within our hospital system to deliver
      real-time notifications in public-facing tasks such as restroom cleanliness and
      critical supply restocking. We expect results from this pilot in the next year.
      CONCLUSIONS: Overall, Internet of Things buttons have significant promise; future
      rigorous evaluations are needed to determine the impact of Internet of Things
      buttons in real-world health care settings.

PMID- 30097421
TI  - Social Media Use in Interventions for Diabetes: Rapid Evidence-Based Review.
AB  - BACKGROUND: Health authorities recommend educating diabetic patients and their
      families and initiating measures aimed at improving self-management, promoting a
      positive behavior change, and reducing the risk of complications. Social media
      could provide valid channel to intervene in and deliver diabetes education.
      However, it is not well known whether the use of these channels in such
      interventions can help improve the patients' outcomes. OBJECTIVE: The objective
      of our study was to review and describe the current existing evidence on the use
      of social media in interventions targeting people affected with diabetes.
      METHODS: A search was conducted across 4 databases (PubMed, Scopus, EMBASE, and
      Cochrane Library).The quality of the evidence of the included primary studies was
      graded according to the Grading of Recommendations Assessment, Development and
      Evaluation criteria, and the risk of bias of systematic reviews was assessed by
      drawing on AMSTAR (A MeaSurement Tool to Assess systematic Reviews) guidelines.
      The outcomes reported by these studies were extracted and analyzed. RESULTS: We
      included 20 moderate- and high-quality studies in the review: 17 primary studies
      and 3 systematic reviews. Of the 16 publications evaluating the effect on
      glycated hemoglobin (HbA1c) of the interventions using social media, 13 reported
      significant reductions in HbA1c values. The 5 studies that measured satisfaction
      with the interventions using social media found positive effects. We found mixed
      evidence regarding the effect of interventions using social media on health
      related quality of life (2 publications found positive effects and 3 found no
      differences) and on diabetes knowledge or empowerment (2 studies reported
      improvements and 2 reported no significant changes). CONCLUSIONS: There is very
      little good-quality evidence on the use of social media in interventions aimed at
      helping people with diabetes. However, the use of these channels is mostly linked
      to benefits on patients' outcomes. Public health institutions, clinicians, and
      other stakeholders who aim at improving the knowledge of diabetic patients could
      consider the use of social media in their interventions.

PMID- 30097424
TI  - Glioblastoma Arises from Cells in the Subventricular Zone.
AB  - Low-level driver mutations in subventricular zone (SVZ) cells are sufficient to
      induce glioblastoma.

PMID- 30097423
TI  - Designing and Implementing a Home-Based Couple Management Guide for Couples Where
      One Partner has Dementia (DemPower): Protocol for a Nonrandomized Feasibility
      Trial.
AB  - BACKGROUND: The increasing rate of dementia and high health and social care costs
      call for effective measures to improve public health and enhance the wellbeing of
      people living with dementia and their relational networks. Most postdiagnostic
      services focus on the condition and the person with dementia with limited
      attention to the caring spouse or partner. The key focus of the study is to
      develop a guide for couples where one partner has a diagnosis of dementia. This
      couple management guide is delivered in the form of an app, DemPower. OBJECTIVE:
      This study aims to investigate the feasibility and acceptability of DemPower and
      to assess the criteria for a full-integrated clinical and economic randomized
      control trial. DemPower couple management app will be introduced to couples
      wherein one partner has dementia. METHODS: The study will recruit 25 couples in
      the United Kingdom and 25 couples in Sweden. Couples will be given 3 months to
      engage with the app, and the amount of time taken to complete the guide (can be
      <3 or >3 months) will be reviewed. A set of outcome measures will be obtained at
      baseline and postintervention stages. RESULTS: The proposed study is at the
      recruitment phase. The DemPower app is being introduced to couples from
      consultation groups at a pretrial phase for identifying any bugs and exploring if
      any navigation challenges exist. The feasibility testing will begin in April
      2018. CONCLUSIONS: The study will determine how much support couples need to
      engage with DemPower and whether or not they make use of it in their everyday
      lives. If there is support for app use, a future study will assess whether it is
      superior to "usual care." TRIAL REGISTRATION: International Standard Randomized
      Controlled Trial Number (ISRCTN): 10122979; http://www.isrctn.com/ISRCTN10122979
      (Archived by WebCite at http://www.webcitation.org/70rB1iWYI). REGISTERED REPORT
      IDENTIFIER: RR1-10.2196/9087.

PMID- 30097422
TI  - Comparing Internet-Based Cognitive Behavioral Therapy With Standard Care for
      Women With Fear of Birth: Randomized Controlled Trial.
AB  - BACKGROUND: Although many pregnant women report fear related to the approaching
      birth, no consensus exists on how fear of birth should be handled in clinical
      care. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy
      of a guided internet-based self-help program based on cognitive behavioral
      therapy (guided ICBT) with standard care on the levels of fear of birth in a
      sample of pregnant women reporting fear of birth. METHODS: This nonblinded,
      multicenter randomized controlled trial with a parallel design was conducted at
      three study centers (hospitals) in Sweden. Recruitment commenced at the
      ultrasound screening examination during gestational weeks 17-20. The therapist
      guided ICBT intervention was inspired by the Unified protocol for transdiagnostic
      treatment of emotional disorders and consisted of 8 treatment modules and 1
      module for postpartum follow-up. The aim was to help participants observe and
      understand their fear of birth and find new ways of coping with difficult
      thoughts and emotions. Standard care was offered in the three different study
      regions. The primary outcome was self-assessed levels of fear of birth, measured
      using the Fear of Birth Scale. RESULTS: We included 258 pregnant women reporting
      clinically significant levels of fear of birth (guided ICBT group, 127; standard
      care group, 131). Of the 127 women randomized to the guided ICBT group, 103 (81%)
      commenced treatment, 60 (47%) moved on to the second module, and only 13 (10%)
      finished >=4 modules. The levels of fear of birth did not differ between the
      intervention groups postintervention. At 1-year postpartum follow-up,
      participants in the guided ICBT group exhibited significantly lower levels of
      fear of birth (U=3674.00, z=-1.97, P=.049, Cohen d=0.28, 95% CI -0.01 to 0.57).
      Using the linear mixed models analysis, an overall decrease in the levels of fear
      of birth over time was found (P<= .001), along with a significant interaction
      between time and intervention, showing a larger reduction in fear of birth in the
      guided ICBT group over time (F1,192.538=4.96, P=.03). CONCLUSIONS: Fear of birth
      decreased over time in both intervention groups; while the decrease was slightly
      larger in the guided ICBT group, the main effect of time alone, regardless of
      treatment allocation, was most evident. Poor treatment adherence to guided ICBT
      implies low feasibility and acceptance of this treatment. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02306434; https://clinicaltrials.gov/ct2/show/NCT02306434
      (Archived by WebCite at http://www.webcitation.org/70sj83qat).

PMID- 30097426
TI  - AKT1 Can Be Activated via Distinct Phosphorylation-Based Mechanisms.
AB  - Phosphorylation of Ser473 and dual phosphorylation of Ser477/Thr479 activate AKT
      via distinct mechanisms.

PMID- 30097425
TI  - ERG Retargets BAF Complexes to Promote Prostate Oncogenesis.
AB  - In TMPRSS2-ERG-positive prostate cancer, ERG retargets BAF chromatin remodeling
      complexes to ETS motifs.

PMID- 30097427
TI  - A KAT6A/B Inhibitor Induces Senescence to Suppress Tumorigenesis.
AB  - The reversible competitive KAT6A/B inhibitor WM-1119 enhanced oncogene-induced
      senescence.

PMID- 30097428
TI  - Criteria led discharge of wheezy children from a short stay assessment unit.
AB  - Implementation and evaluation of criteria led discharge from a short stay
      assessment unit for children with wheeze.

PMID- 30097429
TI  - How to write an Interpretation.
AB  - Every day we interpret examination findings and clinical tests with the aim of
      coming to a diagnosis. But how well do we interpret these tests? Whether it is a
      traditional examination technique used by doctors for centuries or a new cutting
      edge biomarker, the diagnostic landscape shifts over time. The aim of
      interpretations is to produce a library of evidence-based resources directing the
      use of clinical tests including examination techniques. In this article we
      discuss how best to tackle writing an interpretation. Interpretations are
      succinct evidence-based summaries that draw together research findings to provide
      practical answers for clinicians.

PMID- 30097430
TI  - Adolescent girls are susceptible to sexual pressure, coercion and victimisation
      and strategies need to be developed and aimed at males and females to prevent
      this.

PMID- 30097431
TI  - Skills and simulation in nursing: a great opportunity or huge challenge?

PMID- 30097432
TI  - Racial differences and determinants of macular thickness profiles in multiethnic
      Asian population: the Singapore Epidemiology of Eye Diseases Study.
AB  - AIM: To evaluate racial differences, and ocular and systemic determinants of
      macular thickness (MT), measured by spectral-domain optical coherence tomography
      (SD-OCT) in a normal multiethnic Asian population. METHOD: MT was measured from a
      6*6 mm2 central macular area using the Cirrus high-definition OCT (HD-OCT) (Carl
      Zeiss Meditec, Dublin, CA). The associations between ocular and systemic factors
      with MT were evaluated using linear regression analyses with generalised
      estimating equation models to account for intereye correlation. RESULTS: 7447
      healthy eyes (2577 Chinese, 2072 Malays and 2798 Indians) of 4510 subjects were
      included. Multivariable analysis showed that older age (per decade, beta=-4.39),
      female gender (beta=-5.74), diabetes (beta=-1.10), chronic kidney disease (CKD)
      (beta=-3.21), longer axial length (per mm, beta=-2.34), flatter corneal curvature
      (per mm, beta=-1.79) and presence of cataract (beta=-0.94) were associated with
      thinner overall average MT (OMT) (all p<=0.026); higher total cholesterol
      (beta=0.44; p=0.010) was associated with thicker OMT. All these factors were also
      associated with thinner central subfield MT (CSMT) (all p<=0.001), except for
      cataract, total cholesterol and CKD. Meanwhile, longer axial length (beta=2.51;
      p<0.001) was associated with thicker CSMT. OMT (mean+/-SD) was thickest in
      Chinese (279.9+/-12.5 um), followed by Malays (276.5+/-13.7 um) and Indians
      (272.4+/-13.1 um), with p<=0.003 for all interethnic comparisons. Similar trend
      was observed for CSMT. CONCLUSION: There are interethnic differences in MT
      profile among Asians, particularly between Chinese and Indians. Ocular and
      systemic factors affect MT measurements as well. This Asian-specific information
      may be incorporated into existing clinical interpretation of macular OCT scans to
      aid in improving the diagnostic and monitoring accuracy of macular diseases among
      Asians.

PMID- 30097433
TI  - A Phase I/IIa Trial Using CD19-Targeted Third-Generation CAR T Cells for Lymphoma
      and Leukemia.
AB  - Purpose: The chimeric antigen receptor (CAR) T-cell therapy has been effective
      for patients with CD19+ B-cell malignancies. Most studies have investigated the
      second-generation CARs with either CD28 or 4-1BB costimulatory domains in the CAR
      receptor. Here, we describe the first clinical phase I/IIa trial using third
      generation CAR T cells targeting CD19 to evaluate safety and
      efficacy.Experimental Design: Fifteen patients with B-cell lymphoma or leukemia
      were treated with CAR T cells. The patients with lymphoma received chemotherapy
      during CAR manufacture and 11 of 15 were given low-dose cyclophosphamide and
      fludarabine conditioning prior to CAR infusion. Peripheral blood was sampled
      before and at multiple time points after CAR infusion to evaluate the persistence
      of CAR T cells and for immune profiling, using quantitative PCR, flow cytometry,
      and a proteomic array.Results: Treatment with third-generation CAR T cells was
      generally safe with 4 patients requiring hospitalization due to adverse
      reactions. Six of the 15 patients had initial complete responses [4/11 lymphoma
      and 2/4 acute lymphoblastic leukemia (ALL)], and 3 of the patients with lymphoma
      were in remission at 3 months. Two patients are still alive. Best predictor of
      response was a good immune status prior to CAR infusion with high IL12, DC-Lamp,
      Fas ligand, and TRAIL. Responding patients had low monocytic myeloid-derived
      suppressor cells (MDSCs; CD14+CD33+HLA-DR-) and low levels of IL6, IL8, NAP3,
      sPDL1, and sPDL2.Conclusions: Third-generation CARs may be efficient in patients
      with advanced B-cell lymphoproliferative malignancy with only modest toxicity.
      Immune profiling pre- and posttreatment can be used to find response biomarkers.
      Clin Cancer Res; 1-10. (c)2018 AACR.

PMID- 30097434
TI  - A Phase I Trial of a Guadecitabine (SGI-110) and Irinotecan in Metastatic
      Colorectal Cancer Patients Previously Exposed to Irinotecan.
AB  - Purpose: Chemotherapeutic resistance eventually develops in all patients with
      metastatic colorectal cancer (mCRC). Gene silencing through promoter
      demethylation is one potential reversible mechanism of resistance with
      administration of hypomethylating agents. We evaluated the safety and
      tolerability of guadecitabine and irinotecan in patients with mCRC previously
      treated with irinotecan.Experimental Design: In this 3+3 dose-escalation study,
      patients with mCRC previously exposed to irinotecan received guadecitabine days 1
      to 5 of a 28-day cycle and irinotecan 125 mg/m2 days 8 and 15 [dose level (DL) 1,
      guadecitabine 45 mg/m2; DL -1: guadecitabine 30 mg/m2; DL -1G: guadecitabine 30
      mg/m2 with growth factor support (GFS); DL 1G: guadecitabine 45 mg/m2 with
      GFS].Results: Twenty-two patients were treated across four DLs. Dose-limiting
      toxicities were neutropenic fever (DL 1 and -1G), biliary drain infection (DL 
      1), colonic obstruction (DL -1), and severe dehydration (DL 1G). Most common
      toxicities were neutropenia (82% any grade, 77% Grade 3/4), neutropenic fever
      (23%), leukopenia (73% any grade, 50% Grade 3/4), and injection site reactions
      (64% total, 0% Grade 3/4). Patients received a median of 4.5 cycles of treatment;
      12/17 evaluable patients had stable disease as best response, with one having
      initial disease progression but subsequently durable partial response.
      Circulating tumor DNA showed decrease in global demethylation by LINE-1 after
      treatment.Conclusions: We report the first study of chemo-priming with epigenetic
      therapy in gastrointestinal cancers. Guadecitabine 45 mg/m2 and irinotecan 125
      mg/m2 with GFS was safe and tolerable in patients with mCRC, with early
      indication of benefit. These data have provided the basis for an ongoing phase II
      randomized, multicenter trial. Clin Cancer Res; 24(24); 1-8. (c)2018 AACR.

PMID- 30097437
TI  - How do we stop people smoking at the front doors of our hospitals?

PMID- 30097435
TI  - Loss of Nuclear Localized Parathyroid Hormone-Related Protein in Primary Breast
      Cancer Predicts Poor Clinical Outcome and Correlates with Suppressed Stat5
      Signaling.
AB  - Purpose: Parathyroid hormone-related protein (PTHrP) is required for normal
      mammary gland development and biology. A PTHLH gene polymorphism is associated
      with breast cancer risk, and PTHrP promotes growth of osteolytic breast cancer
      bone metastases. Accordingly, current dogma holds that PTHrP is upregulated in
      malignant primary breast tumors, but solid evidence for this assumption is
      missing.Experimental Design: We used quantitative IHC to measure PTHrP in normal
      and malignant breast epithelia, and correlated PTHrP levels in primary breast
      cancer with clinical outcome.Results: PTHrP levels were markedly downregulated in
      malignant compared with normal breast epithelia. Moreover, low levels of nuclear
      localized PTHrP in cancer cells correlated with unfavorable clinical outcome in a
      test and a validation cohort of breast cancer treated at different institutions
      totaling nearly 800 cases. PTHrP mRNA levels in tumors of a third cohort of 737
      patients corroborated this association, also after multivariable adjustment for
      standard clinicopathologic parameters. Breast cancer PTHrP levels correlated
      strongly with transcription factors Stat5a/b, which are established markers of
      favorable prognosis and key mediators of prolactin signaling. Prolactin
      stimulated PTHrP transcript and protein in breast cancer cell lines in vitro and
      in vivo, effects mediated by Stat5 through the P2 gene promoter, producing
      transcript AT6 encoding the PTHrP 1-173 isoform. Low levels of AT6, but not two
      alternative transcripts, correlated with poor clinical outcome.Conclusions: This
      study overturns the prevailing view that PTHrP is upregulated in primary breast
      cancers and identifies a direct prolactin-Stat5-PTHrP axis that is progressively
      lost in more aggressive tumors. Clin Cancer Res; 1-12. (c)2018 AACR.

PMID- 30097436
TI  - Equilibrative Nucleoside Transporter 1 (ENT1, SLC29A1) Facilitates Transfer of
      the Antiretroviral Drug Abacavir across the Placenta.
AB  - Abacavir is a preferred antiretroviral drug for preventing mother-to-child human
      immunodeficiency virus transmission; however, mechanisms of its placental
      transfer have not been satisfactorily described to date. Because abacavir is a
      nucleoside-derived drug, we hypothesized that the nucleoside transporters,
      equilibrative nucleoside transporters (ENTs, SLC29A) and/or Na+-dependent
      concentrative nucleoside transporters (CNTs, SLC28A), may play a role in its
      passage across the placenta. To test this hypothesis, we performed uptake
      experiments using the choriocarcinoma-derived BeWo cell line, human fresh villous
      fragments, and microvillous plasma membrane (MVM) vesicles. Using endogenous
      substrates of nucleoside transporters, [3H]-adenosine (ENTs, CNT2, and CNT3) and
      [3H]-thymidine (ENTs, CNT1, and CNT3), we showed significant activity of ENT1 and
      CNT2 in BeWo cells, whereas experiments in the villous fragments and MVM
      vesicles, representing a model of the apical membrane of a syncytiotrophoblast,
      revealed only ENT1 activity. When testing [3H]-abacavir uptakes, we showed that
      of the nucleoside transporters, ENT1 plays the dominant role in abacavir uptake
      into placental tissues, whereas contribution of Na+-dependent transport, most
      likely mediated by CNTs, was observed only in BeWo cells. Subsequent experiments
      with dually perfused rat term placentas showed that Ent1 contributes
      significantly to overall [3H]-abacavir placental transport. Finally, we
      quantified the expression of SLC29A in first- and third-trimester placentas,
      revealing that SLC29A1 is the dominant isoform. Neither SLC29A1 nor SLC29A2
      expression changed over the course of placental development, but there was
      considerable interindividual variability in their expression. Therefore, drug
      drug interactions and the effect of interindividual variability in placental ENT1
      expression on abacavir disposition into fetal circulation should be further
      investigated to guarantee safe and effective abacavir-based combination therapies
      in pregnancy.

PMID- 30097438
TI  - FinR Regulates Expression of nicC and nicX Operons, Involved in Nicotinic Acid
      Degradation in Pseudomonas putida KT2440.
AB  - Many proteobacteria harbor FinR homologues in their genomes as putative LysR-type
      proteins; however, the function of FinR is poorly studied except in the induction
      of fpr-1 under superoxide stress conditions in Pseudomonas putida and Pseudomonas
      aeruginosa Here, by analyzing the influence of finR deletion on the
      transcriptomic profile of P. putida KT2440 through RNA sequencing and real-time
      quantitative PCR (RT-qPCR), we found 11 operons that are potentially regulated by
      FinR. Among them, the expression of nicC and nicX operons, which were reported to
      be responsible for the aerobic degradation of nicotinic acid (NA), was
      significantly decreased in the finR mutant, and complementation with intact finR
      restored the expression of the two operons. The results of bacterial NA
      utilization demonstrated that the deletion of finR impaired bacterial growth in
      minimal medium supplemented with NA/6HNA (6-hydroxynicotinic acid) as the sole
      carbon source and that complementation with intact finR restored the growth of
      the mutant strain. The expression of nicC and nicX operons was previously
      revealed to be repressed by the NicR repressor and induced by NA/6HNA. Our
      transcriptional assay revealed that the deletion of finR weakened the induction
      of nicC and nicX by NA/6HNA. Meanwhile, the deletion of finR largely decreased
      the effect of nicR deletion on the expression of nicC and nicX operons. These
      results suggest that finR plays a positive role and cooperates with NicR in the
      regulation of nicC and nicX operons. In vitro experiments showed that both FinR
      and NicR bound to nicX and nicC promoter regions directly. The results of this
      study deepened our knowledge of FinR function and nicotinic acid degradation in
      P. putida IMPORTANCE This study analyzed the influence of finR deletion on the
      transcriptomic profile of Pseudomonas putida KT2440. The FinR regulator is widely
      distributed but poorly studied in diverse proteobacteria. Here, we found 11
      operons that potentially are regulated by FinR in KT2440. We further demonstrated
      that FinR played a positive role and cooperated with the NicR repressor in
      bacterial nicotinic acid (NA) degradation via regulating the expression of nicC
      and nicX operons. Furthermore, a transcriptomic analysis also indicated a
      potentially negative role of FinR in the expression of the hut cluster involved
      in bacterial histidine utilization. The work deepened our knowledge of FinR
      function and nicotinic acid degradation in P. putida.

PMID- 30097439
TI  - Enhancement of Bacillus thuringiensis Cry1Ab and Cry1Fa Toxicity to Spodoptera
      frugiperda by Domain III Mutations Indicates There Are Two Limiting Steps in
      Toxicity as Defined by Receptor Binding and Protein Stability.
AB  - Bacillus thuringiensis Cry1Ab and Cry1Fa toxins are environmentally safe
      insecticides that control important insect pests. Spodoptera frugiperda is an
      important maize pest that shows low susceptibility to Cry1A toxins, in contrast
      to Cry1Fa, which is highly active against this pest and is used in transgenic
      maize for S. frugiperda control. The beta16 region from domain III of Cry1Ab has
      been shown to be involved in interactions with receptors such as alkaline
      phosphatase (ALP) or aminopeptidase (APN) in different lepidopteran insects.
      Alanine-scanning mutagenesis of amino acids of Cry1Ab beta16 (509STLRVN514)
      revealed that certain beta16 mutations, such as N514A, resulted in increased
      toxicity of Cry1Ab for S. frugiperda without affecting the toxicity for other
      lepidopteran larvae, such as Manduca sexta larvae. Exhaustive mutagenesis of N514
      was performed, showing that the Cry1Ab N514F, N514H, N514K, N514L, N514Q, and
      N514S mutations increased the toxicity toward S. frugiperda A corresponding
      mutation was constructed in Cry1Fa (N507A). Toxicity assays of wild-type and
      mutant toxins (Cry1Ab, Cry1AbN514A, Cry1AbN514F, Cry1Fa, and Cry1FaN507A) against
      four S. frugiperda populations from Mexico and one from Brazil revealed that
      Cry1AbN514A and Cry1FaN507A consistently showed 3- to 18-fold increased toxicity
      against four of five S. frugiperda populations. In contrast, Cry1AbN514F showed
      increased toxicity in only two of the S. frugiperda populations analyzed. The
      mutants Cry1AbN514A and Cry1AbN514F showed greater stability to midgut protease
      treatment. In addition, binding analysis of the Cry1Ab mutants showed that the
      increased toxicity correlated with increased binding to brush border membrane
      vesicles and increased binding affinity for S. frugiperda ALP, APN, and cadherin
      receptors.IMPORTANCE Spodoptera frugiperda is the main maize pest in South and
      North America and also is an invasive pest in different African countries.
      However, it is poorly controlled by Bacillus thuringiensis Cry1A toxins expressed
      in transgenic crops, which effectively control other lepidopteran pests. In
      contrast, maize expressing Cry1Fa is effective in the control of S. frugiperda,
      although its effectiveness is being lost due to resistance evolution. Some of the
      Cry1Ab domain III mutants characterized here show enhanced toxicity for S.
      frugiperda without loss of toxicity to Manduca sexta Thus, these Cry1Ab mutants
      could provide useful engineered toxins that, along with other Cry toxins, would
      be useful for developing transgenic maize expressing stacked proteins for the
      effective control of S. frugiperda and other lepidopteran pests in the field.

PMID- 30097440
TI  - Boosting Secretion of Extracellular Protein by Escherichia coli via Cell Wall
      Perturbation.
AB  - Escherichia coli is one of the most widely used host microorganisms for
      recombinant protein expression and metabolic engineering, but it cannot
      efficiently secrete recombinant proteins to extracellular space. Here,
      extracellular protein secretion was enhanced in E. coli by deleting two d,d
      carboxypeptidase genes (dacA and dacB, single and double deletions) to perturb
      the cell wall peptidoglycan network. Deletion of dacA and dacB enhanced the
      accumulation of intracellular soluble peptidoglycan in E. coli and affected cell
      morphology, resulting in a more irregular cell shape and the appearance of
      transparent bulges. Deletion of dacA and dacB appears to disrupt the normal rigid
      structure, presumably due to perturbation and destruction of the cell wall
      peptidoglycan network. The extracellular green fluorescent protein (GFP)
      fluorescence intensity of deletion mutants was increased by >2.0-fold compared
      with that of control cells, and that of the double deletion mutant was increased
      by 2.7-fold. Extracellular recombinant fibroblast growth factor receptor 2
      (FGFR2) and collagen E4 secretion in deletion mutants was also enhanced compared
      with that in the control cells. Additionally, the extracellular recombinant
      amylase activity of single-deletion mutants BL21 DeltadacA pETDuet-amyk and BL21
      DeltadacB pETDuet-amyk was increased 2.5- and 3.1-fold, respectively. The
      extracellular distribution of alpha-galactosidase by deletion mutants was also
      increased by >2.0-fold. Deletion of dacA and dacB increased outer membrane
      permeability, which could explain the enhanced extracellular protein
      secretion.IMPORTANCE Cell surface structure stabilization is important for
      extracellular secretion of proteins in Escherichia coli As the main constituent
      of the cell wall, peptidoglycan contributes to cell structure robustness and
      stability. Here, we perturbed the peptidoglycan network by deleting dacA and dacB
      genes encoding d,d-carboxypeptidase enzymes to improve extracellular protein
      secretion. This new strategy could enhance the capacity of E. coli as a microbial
      cell factory for extracellular secretion of proteins and chemicals.

PMID- 30097441
TI  - Vesicular Delivery of the Antifungal Antibiotics of Lysobacter enzymogenes C3.
AB  - Lysobacter enzymogenes C3 is a predatory strain of Gram-negative gliding bacteria
      that produces antifungal antibiotics by the polyketide synthetic pathway. Outer
      membrane vesicles (OMV) are formed as a stress response and can deliver virulence
      factors to host cells. The production of OMV by C3 and their role in antifungal
      activity are reported here. Vesicles in the range of 130 to 150 nm in diameter
      were discovered in the cell-free supernatants of C3 cultures. These OMV contain
      molecules characteristic of bacterial outer membranes, such as lipopolysaccharide
      and phospholipids. In addition, they contain chitinase activity and essentially
      all of the heat-stable antifungal activity in cell supernatants. We show here
      that C3 OMV can directly inhibit growth of the yeast Saccharomyces cerevisiae as
      well as that of the filamentous fungus Fusarium subglutinans The activity is
      dependent on physical contact between OMV and the cells. Furthermore, fluorescent
      lipid labeling of C3 OMV demonstrated transfer of the membrane-associated probe
      to yeast cells, suggesting the existence of a mechanism of delivery for membrane
      associated molecules. Mass spectrometric analysis of C3 OMV extracts indicates
      the presence of molecules with molecular weights identical to some of the
      previously identified antifungal products of C3. These data together suggest that
      OMV act as an important remote mobile component of predation by Lysobacter
      IMPORTANCE The data presented here suggest a newly discovered function of outer
      membrane vesicles (OMV) that are produced from the outer membrane of the
      bacterial species Lysobacter enzymogenes strain C3. We show that these OMV can be
      released from the surface of the cells to deliver antibiotics to target fungal
      organisms as a mechanism of killing or growth inhibition. Understanding the role
      of OMV in antibiotic delivery can generally lead to improved strategies for
      dealing with antibiotic-resistant organisms. These results also add to the
      evidence that some bacterially produced antibiotics can be discovered and
      purified using methods designed for isolation of nanoscale vesicles. Information
      on these systems can lead to better identification of active molecules or design
      of delivery vehicles for these molecules.

PMID- 30097442
TI  - Multi-omic analyses of extensively decayed Pinus contorta reveal expression of
      diverse array of lignocellulose degrading enzymes.
AB  - Fungi play a key role cycling nutrients in forest ecosystems but the mechanisms
      remain uncertain. To clarify the enzymatic processes involved in wood
      decomposition, metatranscriptomics and metaproteomics of extensively decayed
      lodgepole pine were examined by RNAseq and LC-MS/MS, respectively. Following de
      novo metatranscriptome assembly, 52,011 contigs were searched for functional
      domains and homology to database entries. Contigs similar to to basidiomycete
      transcripts dominated and many of these were most closely related to ligninolytic
      white rot fungi or cellulolytic brown rot fungi. A diverse array of carbohydrate
      active enzymes (CAzymes) representing a total of 132 families or subfamilies were
      identified. Among these were 672 glycoside hydrolases including highly expressed
      cellulases or hemicellulases. The CAzymes also included 162 genes encoding redox
      enzymes classified within Auxiliary Activity (AA) families. Eighteen of these
      were manganese peroxidases, key components of ligninolytic white rot fungi.
      Expression of other redox enzymes supported the working of hydroquinone reduction
      cycles capable of generating reactive hydroxyl radical. The latter has been
      implicated as a diffusible oxidant responsible for cellulose depolymerization by
      brown rot fungi. Thus, enzyme diversity and the coexistence of brown and white
      rot fungi suggest complex interactions of fungal species and degradative
      strategies during the decay of logdepole pine.IMPORTANCE The deconstruction of
      recalcitrant woody substrates is a central component of carbon cycling and forest
      health. Laboratory investigations have contributed substantially toward
      understanding mechanisms employed by model wood decay fungi, but few studies have
      examined the physiological processes in natural environments. Herein, we identify
      the functional genes present in field samples of extensively decayed lodgepole
      pine (Pinus contorta), a major species distributed throughout the North American
      Rocky Mountains. The classified transcripts and proteins revealed a diverse array
      of oxidative and hydrolytic enzymes involved in the degradation of
      lignocellulose. The evidence also strongly supports simultaneous attack by fungal
      species employing different enzymatic strategies.

PMID- 30097443
TI  - Formate and Hydrogen as Electron Shuttles in Terminal Fermentations in an
      Oligotrophic Freshwater Lake Sediment.
AB  - The energetic situation of terminal fermentations in methanogenesis was analyzed
      by pool size determinations in sediment cores taken in the oligotrophic Lake
      Constance, Germany. Distribution profiles of fermentation intermediates and
      products were measured at three different water depths (2, 10, and 80 m). Methane
      concentrations were constant below 10 cm of sediment depth. Within the
      methanogenic zone, concentrations of formate, acetate, propionate, and butyrate
      varied between 1 and 40 MUM, and hydrogen was between 0.5 and 5 Pa. From the
      distribution profiles of the fermentation intermediates, Gibbs free energy
      changes for their interconversion were calculated. Pool sizes of formate and
      hydrogen were energetically nearly equivalent, with -5 +/- 5 kJ per mol
      difference of free energy change (DeltaG) for a hypothetical conversion of
      formate to hydrogen plus CO2 The DeltaG values for conversion of fatty acids to
      methanogenic substrates and their further conversion to methane and CO2 were
      calculated with hydrogen and with formate as intermediates. Syntrophic propionate
      oxidation reached energetic equilibrium with formate as the sole electron carrier
      but was sufficiently exergonic if at least some of the electrons were transferred
      via hydrogen. The energetic consequences of formate versus hydrogen transfer in
      secondary and methanogenic fermentations indicate that both carrier systems are
      probably used simultaneously to optimize the energy yields for the partners
      involved.IMPORTANCE In the terminal steps of methane formation in freshwater lake
      sediments, fermenting bacteria cooperate syntrophically with methanogens and
      homoacetogens at minimum energy increments via interspecies electron transfer.
      The energy yields of the partner organisms in these cooperations have so far been
      calculated based mainly on in situ hydrogen partial pressures. In the present
      study, we also analyzed pools of formate as an alternative electron carrier in
      sediment cores of an oligotrophic lake. The formate and hydrogen pools appeared
      to be energetically nearly equivalent and are likely to be used simultaneously
      for interspecies electron transfer. Calculations of reaction energies of the
      partners involved suggest that propionate degradation may also proceed through
      the Smithella pathway, which converts propionate via butyrate and acetate to
      three acetate residues, thus circumventing one energetically difficult fatty acid
      oxidation step.

PMID- 30097445
TI  - Microbial Source Tracking Using Quantitative and Digital PCR To Identify Sources
      of Fecal Contamination in Stormwater, River Water, and Beach Water in a Great
      Lakes Area of Concern.
AB  - Areas of concern (AOCs) around the Great Lakes are characterized by historic and
      ongoing problems with microbial water quality, leading to beneficial use
      impairments (BUIs) such as beach postings and closures. In this study, we
      assessed river and beach sites within the Rouge River watershed, associated
      stormwater outfalls, and at Rouge Beach. The concentrations of Escherichia coli
      as well as human- and gull-specific qPCR microbial source tracking (MST) markers
      were assessed at all sites. A preliminary comparison of digital PCR (dPCR)
      methodologies for both MST markers was conducted regarding sensitivity and
      specificity. Within the watershed, the outfalls were found to be a prominent
      source of human fecal contamination, with two outfalls particularly affected by
      sewage cross-connections. However, the occurrence of human fecal contamination
      along Rouge Beach and in the lower portions of the watershed was largely
      dependent on rain events. Gull fecal contamination was the predominant source of
      contamination at the beach, particularly during dry weather. The multiplex
      human/gull dPCR methodology used in this study tended to be more sensitive than
      the individual quantitative PCR (qPCR) assays, with only a slight decrease in
      specificity. Both dPCR and qPCR methodologies identified the same predominance of
      human and gull markers in stormwater and beach locations, respectively; however,
      the dPCR multiplex assay was more sensitive and capable of detecting fecal
      contamination that was undetected by qPCR assays. These results demonstrate the
      dPCR assay used in this study could be a viable tool for MST studies to increase
      the ability to identify low levels of fecal contamination.IMPORTANCE Fecal
      contamination of recreational water poses a persistent and ongoing problem,
      particularly in areas of concern around the Great Lakes. The identification of
      the source(s) of fecal contamination is essential for safeguarding public health
      as well as guiding remediation efforts; however, fecal contamination may
      frequently be present at low levels and remain undetectable by certain
      methodologies. In this study, we utilized microbial source tracking techniques
      using both quantitative and digital PCR assays to identify sources of
      contamination. Our results indicated high levels of human fecal contamination
      within stormwater outfalls, while lower levels were observed throughout the
      watershed. Additionally, high levels of gull fecal contamination were detected at
      Rouge Beach, particularly during drier sampling events. Furthermore, our results
      indicated an increased sensitivity of the digital PCR assay to detect both human
      and gull contamination, suggesting it could be a viable tool for future microbial
      source tracking studies.

PMID- 30097444
TI  - OpuF: a new Bacillus compatible solute ABC transporter with a substrate-binding
      protein fused to the trans-membrane domain.
AB  - The accumulation of compatible solutes is a common defense of bacteria against
      the detrimental effects of high osmolarity. Uptake systems for these compounds
      are cornerstones in cellular osmostress responses because they allow the energy
      preserving scavenging of osmostress protectants from environmental sources.
      Bacillus subtilis is well studied with respect to the import of compatible
      solutes and its five transport systems (OpuA, OpuB, OpuC, OpuD, OpuE) for these
      stress protectants have previously been comprehensively studied. Building on this
      knowledge and taking advantage of the unabated appearance of new genome sequences
      of members of the genus Bacillus, we report here the discovery, physiological
      characterization, and phylogenomics of a new member of the Opu family of
      transporters, OpuF (OpuFA-OpuFB). OpuF is not present in B. subtilis but it is
      widely distributed in members of the large Bacillus genus. OpuF is a
      representative of a sub-group of ABC transporters in which the substrate-binding
      protein (SBP) is fused to the trans-membrane domain (TMD). We studied the salient
      features of the OpuF transporters from Bacilllus infantis and Bacillus
      panaciterrae by functional reconstitution in a B. subtilis chassis strain lacking
      known Opu transporters. A common property of the examined OpuF systems is their
      substrate profile; OpuF mediates the import of glycine betaine, proline betaine,
      homobetaine and the marine osmolyte dimethylsulfoniopropionate (DMSP). An in
      silico model of the SBP domain of the TMD-SPB hybrid protein OpuFB was
      established. It revealed the presence of an aromatic cage, a structural feature
      commonly present in ligand-binding sites of compatible solute
      importers.IMPORTANCE The high affinity import of compatible solutes from
      environmental sources is an important aspect of the cellular defense of many
      Bacteria and Archaea against the harmful effects of high external osmolarity. The
      accumulation of these osmostress protectants counteracts high osmolarity
      instigated water efflux, drop in turgor to non-physiological values, and an undue
      increase in molecular crowding of the cytoplasm; they thereby foster microbial
      growth under osmotically unfavorable conditions. Importers for compatible solutes
      allow the energy-preserving scavenging of osmoprotective and physiologically
      compliant organic solutes from environmental sources. We report here the
      discovery, exemplary physiological characterization, and phylogenomics of a new
      compatible solute importer (OpuF) widely found in members of the Bacillus genus.
      The OpuF system is a representative of a growing sub-group of ABC transporters in
      which the substrate-scavenging function of the substrate-binding protein (SBP)
      and the membrane-embedded substrate trans-locating subunit (TMD) are fused into a
      single polypeptide chain.

PMID- 30097446
TI  - Complex Iron Uptake by the Putrebactin-Mediated and Feo Systems in Shewanella
      oneidensis.
AB  - Shewanella oneidensis is an extensively studied bacterium capable of respiring
      minerals, including a variety of iron ores, as terminal electron acceptors (EAs).
      Although iron plays an essential and special role in iron respiration of S.
      oneidensis, little has been done to date to investigate the characteristics of
      iron transport in this bacterium. In this study, we found that all proteins
      encoded by the pub-putA-putB cluster for putrebactin (S. oneidensis native
      siderophore) synthesis (PubABC), recognition-transport of Fe3+-putrebactin across
      the outer membrane (PutA), and reduction of ferric putrebactin (PutB) are
      essential to putrebactin-mediated iron uptake. Although homologs of PutA are
      many, none can function as its replacement, but some are able to work with other
      bacterial siderophores. We then showed that Fe2+-specific Feo is the other
      primary iron uptake system, based on the synthetical lethal phenotype resulting
      from the loss of both iron uptake routes. The role of the Feo system in iron
      uptake appears to be more critical, as growth is significantly impaired by the
      absence of the system but not of putrebactin. Furthermore, we demonstrate that
      hydroxyl acids, especially alpha-types such as lactate, promote iron uptake in a
      Feo-dependent manner. Overall, our findings underscore the importance of the
      ferrous iron uptake system in metal-reducing bacteria, providing an insight into
      iron homeostasis by linking these two biological processes.IMPORTANCE S.
      oneidensis is among the first- and the best-studied metal-reducing bacteria, with
      great potential in bioremediation and biotechnology. However, many questions
      regarding mechanisms closely associated with those applications, such as iron
      homeostasis, including iron uptake, export, and regulation, remain to be
      addressed. Here we show that Feo is a primary player in iron uptake in addition
      to the siderophore-dependent route. The investigation also resolved a few puzzles
      regarding the unexpected phenotypes of the putA mutant and lactate-dependent iron
      uptake. By elucidating the physiological roles of these two important iron uptake
      systems, this work revealed the breadth of the impacts of iron uptake systems on
      the biological processes.

PMID- 30097447
TI  - Broad Phylogenetic Diversity Associated with Nitrogen Loss through Sulfur
      Oxidation in a Large Public Marine Aquarium.
AB  - Denitrification by sulfur-oxidizing bacteria is an effective nitrate removal
      strategy in engineered aquatic systems. However, the community taxonomic and
      metabolic diversity of sulfur-driven denitrification (SDN) systems, as well as
      the relationship between nitrate removal and SDN community structure, remains
      underexplored. This is particularly true for SDN reactors applied to marine
      aquaria, despite the increasing use of this technology to supplement filtration.
      We applied 16S rRNA gene, metagenomic, and metatranscriptomic analyses to explore
      the microbial basis of SDN reactors operating on Georgia Aquarium's Ocean
      Voyager, the largest indoor closed-system seawater exhibit in the United States.
      The exhibit's two SDN systems vary in water retention time and nitrate removal
      efficiency. The systems also support significantly different microbial
      communities. These communities contain canonical SDN bacteria, including a strain
      related to Thiobacillus thioparus that dominates the system with the higher water
      retention time and nitrate removal but is effectively absent from the other
      system. Both systems contain a wide diversity of other microbes whose metagenome
      assembled genomes contain genes of SDN metabolism. These include hundreds of
      strains of the epsilonproteobacterium Sulfurimonas, as well as
      gammaproteobacterial sulfur oxidizers of the Thiotrichales and Chromatiales, and
      a relative of Sedimenticola thiotaurini with complete denitrification potential.
      The SDN genes are transcribed and the taxonomic richness of the transcript pool
      varies markedly among the enzymatic steps, with some steps dominated by
      transcripts from noncanonical SDN taxa. These results indicate complex and
      variable SDN communities that may involve chemical dependencies among taxa as
      well as the potential for altering community structure to optimize nitrate
      removal.IMPORTANCE Engineered aquatic systems such as aquaria and aquaculture
      facilities have large societal value. Ensuring the health of animals in these
      systems requires understanding how microorganisms contribute to chemical cycling
      and waste removal. Focusing on the largest seawater aquarium in the United
      States, we explore the microbial communities in specialized reactors designed to
      remove excess nitrogen through the metabolic activity of sulfur-consuming
      microbes. We show that the diversity of microbes in these reactors is both high
      and highly variable, with distinct community types associated with significant
      differences in nitrogen removal rate. We also show that the genes encoding the
      metabolic steps of nitrogen removal are distributed broadly throughout community
      members, suggesting that the chemical transformations in this system are likely a
      result of microbes relying on other microbes. These results provide a framework
      for future studies exploring the contributions of different community members,
      both in waste removal and in structuring microbial biodiversity.

PMID- 30097448
TI  - Orthologues of Bacillus subtilis spore crust proteins have a structural role in
      the Bacillus megaterium QM B1551 spore exosporium.
AB  - The exosporium of Bacillus megaterium QM B1551 spores is morphologically distinct
      to exosporia observed in spores of many other species. Previous work has
      demonstrated that unidentified genes encoded on one of the large indigenous
      plasmids are required for the assembly of the Bacillus megaterium exosporium.
      Here we provide evidence that pBM600-encoded orthologues of the Bacillus subtilis
      CotW and CotX proteins, which form the crust layer in spores of that species, are
      structural components of the Bacillus megaterium QM B1551 spore exosporium. The
      introduction of plasmid-borne cotW and orthologous cotX genes to the PV361
      strain, which lacks all indigenous plasmids and produces spores that are devoid
      of an exosporium, results in the development of spores with a rudimentary
      exosporium-type structure. Additionally, purified recombinant CotW protein is
      shown to assemble at the air-water interface to form thin sheets of material,
      which is consistent with the idea that this protein may form a basal layer in the
      Bacillus megaterium QM B1551 exosporium.Importance When starved of nutrients some
      bacterial species develop metabolically dormant spores that can persist in a
      viable state in the environment for several years. The outermost layers of spores
      are of particular interest since (a) these represent the primary site for
      interaction with the environment, and (b) the protein constituents may have
      biotechnological applications. The outermost layer, or exosporium, in Bacillus
      megaterium QM B1551 spores, is of interest as it is morphologically distinct to
      the exosporium of spores of the pathogenic Bacillus cereus family. In this work
      we provide evidence that structurally important protein constituents of the
      Bacillus megaterium exosporium are different to those in the Bacillus cereus
      family. We show also that one of these proteins can assemble when purified to
      form sheets of exosporium-like material. This is significant as it indicates that
      spore-forming bacteria employ different proteins, and mechanisms of assembly, to
      construct their external layers.

PMID- 30097449
TI  - Elevated Inactivation Efficacy of a Pulsed UVC Light-Emitting Diode System for
      Foodborne Pathogens on Selective Media and Food Surfaces.
AB  - UVC light, a strong surface disinfection technology, is used worldwide to ensure
      not only environmental safety but also food safety. Several drawbacks associated
      with the use of mercury-containing UV lamps, especially human and environmental
      health risks, led to the Minamata Convention on Mercury, which prohibits the
      manufacture and import/export of products containing mercury. Therefore, light
      emitting diode (LED)-based UVC irradiation, a new technology that is ecofriendly
      and represents an effective UV light source, has been researched recently. To
      date, however, there has been no report describing pulsed UVC-LED irradiation for
      improvement of inactivation of foodborne pathogens, although much research
      regarding conventional pulsed xenon lamps has been published. In this
      investigation, we evaluated the enhanced bactericidal effect of a pulsed UVC-LED
      system, compared to continuous irradiation, and optimum conditions for maximizing
      the effect were determined. Also, the differences in inactivation between pulsed
      and continuous UVC-LED irradiation were determined by inactivation mechanism
      analyses. The combination of 20-Hz frequency and 50% duty ratio for pulsed UVC
      LED irradiation achieved 4- to 5-log-unit reductions of Escherichia coli O157:H7,
      Salmonella enterica serovar Typhimurium, and Listeria monocytogenes; this
      combination showed the greatest bactericidal effect among various treatment
      conditions using 2 or 5 mJ/cm2 In mechanism assessments, membrane integrity
      (propidium iodide uptake) was not affected by UVC-LED treatment but membrane
      potential [bis-(1,3-dibutylbarbituric acid)trimethine oxonol [DiBAC4(3)]
      accumulation] showed significantly different values when pulsed and continuous
      treatments were compared. Changes in membrane lipid peroxidation and respiratory
      enzyme activity were attributed to generation of more reactive oxygen species by
      pulsed UVC-LED irradiation.IMPORTANCE In 2013, the United Nations Environment
      Programme convened the Minamata Convention on Mercury, which prohibits trade in
      mercury-containing products in order to ensure human health. It will be
      effectuated in 2020; use of low-pressure mercury lamps will be discontinued and a
      new UV light source selected to replace the conventional technology. In this
      regard, UVC-LEDs have been developed and the fundamental inactivating effect has
      been researched. However, a pulsed UVC-LED system has not been studied, because
      of the difficulty of generating a UVC-LED pulse wave. An optical chopper system
      that physically divides the light with an adjustable blade, with personalized
      frequency and duty ratio settings, was introduced for generation of pulsed UVC
      LED irradiation. This study elucidated the efficacy of a pulsed UVC-LED system
      and investigated its enhanced bactericidal effect in mechanism analyses.

PMID- 30097450
TI  - Locum oncologist has been struck off for death of patient in India.

PMID- 30097451
TI  - Trust in GPs remains high but patients report more difficulties getting an
      appointment.

PMID- 30097453
TI  - Early identification of rheumatoid arthritis: the risk of overtreatment in
      perspective.

PMID- 30097452
TI  - Interleukin 12 and interleukin 23 play key pathogenic roles in inflammatory and
      proliferative pathways in giant cell arteritis.
AB  - OBJECTIVES: The pathogenesis of giant cell arteritis (GCA) remains unclear. TH1
      and TH17 pathways are implicated, but the proximal initiators and effector
      cytokines are unknown. Our aim was to assess the role of interleukin 12 (IL-12)
      and interleukin 23 (IL-23) in GCA pathogenesis. METHODS: IL-12 and IL-23
      expression were quantified by immunohistochemistry in temporal artery biopsies
      (TABs). Temporal artery (TA) explant, peripheral blood mononuclear cell (PBMC)
      and myofibroblast outgrowth culture models were established. PBMCs and TA
      explants were cultured for 24 hours in the presence or absence of IL-12 (50
      ng/mL) or IL-23 (10 ng/mL). Gene expression in TA was quantified by real-time PCR
      and cytokine secretion by ELISA. Myofibroblast outgrowths were quantified
      following 28-day culture. RESULTS: Immunohistochemistry demonstrated increased
      expression of interleukin 12p35 (IL-12p35) and interleukin 23p19 (IL-23p19) in
      biopsy-positive TAs, localised to inflammatory cells. IL-12p35 TA expression was
      significantly increased in those with cranial ischaemic complications (p=0.026)
      and large vessel vasculitis (p=0.006). IL-23p19 TA expression was increased in
      those with two or more relapses (p=0.007). In PBMC cultures, exogenous IL-12
      significantly increased interleukin 6 (IL-6) (p=0.009), interleukin 22 (IL-22)
      (p=0.003) and interferon gamma (IFN-gamma) (p=0.0001) and decreased interleukin 8
      (IL-8) (p=0.0006) secretion, while exogenous IL-23 significantly increased IL-6
      (p=0.029), IL-22 (p=0.001), interleukin 17A (IL-17A) (p=0.0003) and interleukin
      17F (IL-17F) (p=0.012) secretion. In ex vivo TA explants, IL-23 significantly
      increased gene expression of IL-8 (p=0.0001) and CCL-20 (p=0.027) and protein
      expression of IL-6 (p=0.002) and IL-8 (p=0.004). IL-12 (p=0.0005) and IL-23
      (p<0.0001) stimulation increased the quantity of myofibroblast outgrowths from
      TABs. CONCLUSION: IL-12 and IL-23 play central and distinct roles in stimulating
      inflammatory and proliferative pathways relevant to GCA pathogenesis.

PMID- 30097454
TI  - Improved detection of erosions in the sacroiliac joints on MRI with volumetric
      interpolated breath-hold examination (VIBE): results from the SIMACT study.
AB  - OBJECTIVE: To compare the performance of a new three-dimensional MRI sequence
      (volumetric interpolated breath-hold examination; MR-VIBE) with a conventional T1
      weighted sequence (MR-T1) for the detection of erosions in the sacroiliac joints
      (SIJs) using low-dose CT (ldCT) as reference. METHODS: ldCT and T1-MRI and MR
      VIBE of 110 prospectively included patients with low back pain and suspected
      axial spondyloarthritis (axSpA) were scored for erosions by two readers. The
      presence of erosions on the patients' level, the erosion sum score, sensitivity
      and specificity of both MRI sequences using ldCT as a reference as well as
      agreement between the readers were assessed. RESULTS: MR-VIBE had a higher
      sensitivity than MR-T1 (95% vs 79%, respectively) without a decrease in
      specificity (93% each). MR-VIBE compared with MR-T1 identified 16% more patients
      with erosions (36 vs 30 of 38 patients with positive ldCT findings). The erosion
      sum score was also higher for MR-VIBE (8.1+/-9.3) than MR-T1 (6.7+/-8.4),
      p=0.003. The agreement on erosion detection was also higher for MR-VIBE
      (kappa=0.71) compared with MRI-T1 (kappa=0.56). CONCLUSION: VIBE detected
      erosions in the SIJs with higher sensitivity without a loss of specificity and
      superior reliability compared with a standard T1-weighted sequence. Its value for
      the diagnosis of axSpA has still to be determined.

PMID- 30097455
TI  - Response to: 'Early identification of rheumatoid arthritis; the risk of
      overtreatment in perspective' by Landewe.

PMID- 30097456
TI  - Could this be whooping cough?
AB  - Whooping cough is a notifiable bacterial respiratory infection caused by
      Bordetella pertussis It may produce serious disease, especially in
      immunocompromised individuals and very young children. The number of reported
      cases increases in the winter months and the incidence peaks every 4-5 years.
      However, this periodicity is variable and is inconsistent between different
      geographical regions. Bordetella pertussis infection (BPI) may be underdiagnosed
      because of its seasonality and the fact that clinical features may be
      indistinguishable from other respiratory disorders in the paediatric ED setting.
      Treatment with antibiotics reduces the period of infectivity but may not shorten
      the illness. This review discusses the epidemiology of the disease, its clinical
      features, diagnosis, treatment and the disposition of patients with BPI.

PMID- 30097457
TI  - FLYWCH1, a Novel Suppressor of Nuclear beta-Catenin, Regulates Migration and
      Morphology in Colorectal Cancer.
AB  - : Wnt/beta-catenin signaling plays a critical role during development of both
      normal and malignant colorectal cancer tissues. Phosphorylation of beta-catenin
      protein alters its trafficking and function. Such conventional allosteric
      regulation usually involves a highly specialized set of molecular interactions,
      which may specifically turn on a particular cell phenotype. This study identifies
      a novel transcription modulator with an FLYWCH/Zn-finger DNA-binding domain,
      called "FLYWCH1." Using a modified yeast-2-hybrid based Ras-Recruitment system,
      it is demonstrated that FLYWCH1 directly binds to unphosphorylated (nuclear) beta
      catenin efficiently suppressing the transcriptional activity of Wnt/beta-catenin
      signaling that cannot be rescued by TCF4. FLYWCH1 rearranges the transcriptional
      activity of beta-catenin/TCF4 to selectively block the expression of specific
      downstream genes associated with colorectal cancer cell migration and morphology,
      including ZEB1, EPHA4, and E-cadherin. Accordingly, overexpression of FLYWCH1
      reduces cell motility and increases cell attachment. The expression of FLYWCH1
      negatively correlates with the expression level of ZEB1 and EPHA4 in normal
      versus primary and metastatic colorectal cancer tissues in patients. Thus,
      FLYWCH1 antagonizes beta-catenin/TCF4 signaling during cell polarity/migration in
      colorectal cancer. IMPLICATIONS: This study uncovers a new molecular mechanism by
      which FLYWCH1 with a possible tumor suppressive role represses beta-catenin
      induced ZEB1 and increases cadherin-mediated cell attachment preventing
      colorectal cancer metastasis.

PMID- 30097459
TI  - Artificial womb technology and the frontiers of human reproduction: conceptual
      differences and potential implications.
AB  - In 2017, a Philadelphia research team revealed the closest thing to an artificial
      womb (AW) the world had ever seen. The 'biobag', if as successful as early animal
      testing suggests, will change the face of neonatal intensive care. At present,
      premature neonates born earlier than 22 weeks have no hope of survival. For some
      time, there have been no significant improvements in mortality rates or
      incidences of long-term complications for preterms at the viability threshold.
      Artificial womb technology (AWT), that might change these odds, is eagerly
      anticipated for clinical application. We need to understand whether AWT is an
      extension of current intensive care or something entirely new. This question is
      central to determining when and how the biobag should be used on human subjects.
      This paper examines the science behind AWT and advances two principal claims.
      First, AWT is conceptually different from conventional intensive care.
      Identifying why AWT should be understood as distinct demonstrates how it raises
      different ethico-legal questions. Second, these questions should be formulated
      without the 'human being growing in the AW' being described with inherently value
      laden terminology. The 'human being in an AW' is neither a fetus nor a baby, and
      the ethical tethers associated with these terms could perpetuate misunderstanding
      and confusion. Thus, the term 'gestateling' should be adopted to refer to this
      new product of human reproduction: a developing human being gestating ex utero.
      While this paper does not attempt to solve all the ethical problems associated
      with AWT, it makes important clarifications that will enable better formulation
      of relevant ethical questions for future exploration.

PMID- 30097458
TI  - Mechanism of Fibrosis in HNF1B-Related Autosomal Dominant Tubulointerstitial
      Kidney Disease.
AB  - BACKGROUND: Mutation of HNF1B, the gene encoding transcription factor HNF-1beta,
      is one cause of autosomal dominant tubulointerstitial kidney disease, a syndrome
      characterized by tubular cysts, renal fibrosis, and progressive decline in renal
      function. HNF-1beta has also been implicated in epithelial-mesenchymal transition
      (EMT) pathways, and sustained EMT is associated with tissue fibrosis. The
      mechanism whereby mutated HNF1B leads to tubulointerstitial fibrosis is not
      known. METHODS: To explore the mechanism of fibrosis, we created HNF-1beta
      deficient mIMCD3 renal epithelial cells, used RNA-sequencing analysis to reveal
      differentially expressed genes in wild-type and HNF-1beta-deficient mIMCD3 cells,
      and performed cell lineage analysis in HNF-1beta mutant mice. RESULTS: The HNF
      1beta-deficient cells exhibited properties characteristic of mesenchymal cells
      such as fibroblasts, including spindle-shaped morphology, loss of contact
      inhibition, and increased cell migration. These cells also showed upregulation of
      fibrosis and EMT pathways, including upregulation of Twist2, Snail1, Snail2, and
      Zeb2, which are key EMT transcription factors. Mechanistically, HNF-1beta
      directly represses Twist2, and ablation of Twist2 partially rescued the
      fibroblastic phenotype of HNF-1beta mutant cells. Kidneys from HNF-1beta mutant
      mice showed increased expression of Twist2 and its downstream target Snai2. Cell
      lineage analysis indicated that HNF-1beta mutant epithelial cells do not
      transdifferentiate into kidney myofibroblasts. Rather, HNF-1beta mutant
      epithelial cells secrete high levels of TGF-beta ligands that activate downstream
      Smad transcription factors in renal interstitial cells. CONCLUSIONS: Ablation of
      HNF-1beta in renal epithelial cells leads to the activation of a Twist2-dependent
      transcriptional network that induces EMT and aberrant TGF-beta signaling,
      resulting in renal fibrosis through a cell-nonautonomous mechanism.

PMID- 30097461
TI  - Cost-effectiveness of ibrutinib as first-line therapy for chronic lymphocytic
      leukemia in older adults without deletion 17p.
AB  - Ibrutinib is a novel oral therapy that has shown significant efficacy as initial
      treatment of chronic lymphocytic leukemia (CLL). It is a high-cost continuous
      therapy differing from other regimens that are given for much shorter courses.
      Our objective was to evaluate the cost-effectiveness of ibrutinib for first-line
      treatment of CLL in patients older than age 65 years without a 17p deletion. We
      developed a semi-Markov model to analyze the cost-effectiveness of ibrutinib vs a
      comparator therapy from a US Medicare perspective. No direct comparison between
      ibrutinib and the best available treatment alternative, obinutuzumab plus
      chlorambucil (chemoimmunotherapy), exists. Therefore, we compared ibrutinib to a
      theoretical treatment alternative, which was modeled to confer the effectiveness
      of an inferior treatment (chlorambucil alone) and the costs and adverse events of
      chemoimmunotherapy, which would provide ibrutinib with the best chance of being
      cost-effective. Even so, the incremental cost-effectiveness ratio of ibrutinib vs
      the modeled comparator was $189 000 per quality-adjusted life-year (QALY) gained.
      To reach a willingness-to-pay threshold (WTP) of $150 000 per QALY, the monthly
      cost of ibrutinib would have to be at most $6800, $1700 less than the modeled
      cost of $8500 per month (a reduction of $20 400 per year). When the comparator
      efficacy is increased to more closely match that seen in trials evaluating
      chemoimmunotherapy, ibrutinib costs more than $262 000 per QALY gained, and the
      monthly cost of ibrutinib would need to be lowered to less than $5000 per month
      to be cost-effective. Ibrutinib is not cost-effective as initial therapy at a WTP
      threshold of $150 000 per QALY gained.

PMID- 30097460
TI  - Corticosteroid therapy for sepsis: a clinical practice guideline.

PMID- 30097462
TI  - Elevated ecto-5'-nucleotidase: a missing pathogenic factor and new therapeutic
      target for sickle cell disease.
AB  - Although excessive plasma adenosine is detrimental in sickle cell disease (SCD),
      the molecular mechanism underlying elevated circulating adenosine remains
      unclear. Here we report that the activity of soluble CD73, an ectonucleotidase
      producing extracellular adenosine, was significantly elevated in a murine model
      of SCD and correlated with increased plasma adenosine. Mouse genetic studies
      demonstrated that CD73 activity contributes to excessive induction of plasma
      adenosine and thereby promotes sickling, hemolysis, multiorgan damage, and
      disease progression. Mechanistically, we showed that erythrocyte adenosine 5'
      monophosphate-activated protein kinase (AMPK) was activated both in SCD patients
      and in the murine model of SCD. AMPK functions downstream of adenosine receptor
      ADORA2B signaling and contributes to sickling by regulating the production of
      erythrocyte 2,3-bisphosphoglycerate (2,3-BPG), a negative allosteric regulator of
      hemoglobin-O2 binding affinity. Preclinically, we reported that treatment of
      alpha,beta-methylene adenosine 5'-diphosphate, a potent CD73 specific inhibitor,
      significantly decreased sickling, hemolysis, multiorgan damage, and disease
      progression in the murine model of SCD. Taken together, both human and mouse
      studies reveal a novel molecular mechanism contributing to the pathophysiology of
      SCD and identify potential therapeutic strategies to treat SCD.

PMID- 30097464
TI  - Development of a prognostically relevant cachexia index in primary myelofibrosis
      using serum albumin and cholesterol levels.

PMID- 30097465
TI  - Implementing integrated sexual and reproductive healthcare in a large sexual
      health service in England: challenges and opportunities for the provider.

PMID- 30097466
TI  - Patterns of desmin expression in idiopathic dilated cardiomyopathy are related to
      the desmin mRNA and ubiquitin expression.
AB  - Desmin expression depends on desmin messenger RNA (mRNA) and ubiquitin proteasome
      system. This process is poorly understood in dilated cardiomyopathy. The aim of
      the study was to investigate whether changes of desmin mRNA and ubiquitin
      expression correlate with types of desmin expression in cardiomyocytes.
      Endomyocardial biopsy was performed in 60 patients (85% men, mean age 46+/-14
      years) with heart failure (HF; left ventricular ejection fraction <45%). Desmin
      and ubiquitin expression were analysed in histological sections by
      immunohistochemistry and in Western blot. Desmin mRNA expression was determined
      by fluorescent in situ hybridization methods. In patients with weak/even desmin
      expression, weak/even expression of ubiquitin in the cytosol and low desmin mRNA
      expression in the cytosol and nuclei of cardiomyocytes were observed. Expression
      of ubiquitin and desmin mRNA increased along with the progression of desmin
      cytoskeleton remodeling. Desmin mRNA and ubiquitin were weakly expressed/absent
      in cardiomyocytes with low/lack of desmin expression. Variations in desmin mRNA,
      desmin and ubiquitin expression were associated with gradual changes in
      myocardial structure and clinical parameters. To conclude, changes in ubiquitin
      and desmin mRNA expression are related to patterns of desmin expression. An
      increase in the expression of ubiquitin and desmin mRNA may be a protective
      feature against unfavorable cell remodeling. This may reduce the adverse effects
      of cytoskeleton damage in the early stages of HF. Low/lack ubiquitin and/or
      desmin mRNA expression may be markers of end-stage HF.

PMID- 30097467
TI  - Elephant in the ward: boredom in hospitals.

PMID- 30097463
TI  - Double-blind, randomized, multicenter phase 2 study of SC411 in children with
      sickle cell disease (SCOT trial).
AB  - Blood cell membranes in sickle cell disease (SCD) have low docosahexaenoic acid
      (DHA). DHA treatment reduces sickle cell crisis (SCC) rate and ameliorates the
      inflammation, oxidative stress, and hypercoagulable state of SCD. SC411 is a
      novel DHA ethyl ester formulation with a proprietary delivery platform (Advanced
      Lipid Technology) that enhances DHA bioavailability. The SCOT trial investigated
      the effect of 3 different doses of SC411 on clinical and biochemical endpoints in
      67 children with SCD (5-17 years old). Seventy-six percent of subjects were also
      receiving hydroxyurea. After 4 weeks of treatment with SC411 at 20, 36, and 60 mg
      DHA/kg per day or placebo a statistically significant (P < .001) mean percentage
      increase of blood cell membrane DHA and eicosapentaenoic acid was seen vs
      baseline: 109.0% (confidence interval [CI], 46.7-171.3), 163.8% (CI, 108.3
      219.2), 170.8% (CI, 90.2-251.4), and 28.6% (CI, 250.1 to 107.3), respectively.
      After 8 weeks of treatment, statistically significant changes vs placebo were
      also observed in D-dimer (P = .025) and soluble E-selectin (P = .0219) in
      subjects exposed to 36 mg/kg. A significant increase in hemoglobin was observed
      against placebo in subjects receiving 20 mg DHA/kg per day (P = .039). SC411
      significantly reduced electronic diary recorded SCC, analgesic use at home, and
      days absent from school because of sickle cell pain. The lower rate of clinical
      SCC observed in the pooled active groups vs placebo did not reach statistical
      significance (rate ratio, 0.47; 95% CI, 0.20-1.11; P = .07). All tested doses
      were safe and well tolerated. This trial was registered at www.clinicaltrials.gov
      as #NCT02973360.

PMID- 30097468
TI  - Plant Phenotyping: An Active Vision Cell for Three-Dimensional Plant Shoot
      Reconstruction.
AB  - Three-dimensional (3D) computer-generated models of plants are urgently needed to
      support both phenotyping and simulation-based studies such as photosynthesis
      modeling. However, the construction of accurate 3D plant models is challenging,
      as plants are complex objects with an intricate leaf structure, often consisting
      of thin and highly reflective surfaces that vary in shape and size, forming
      dense, complex, crowded scenes. We address these issues within an image-based
      method by taking an active vision approach, one that investigates the scene to
      intelligently capture images, to image acquisition. Rather than use the same
      camera positions for all plants, our technique is to acquire the images needed to
      reconstruct the target plant, tuning camera placement to match the plant's
      individual structure. Our method also combines volumetric- and surface-based
      reconstruction methods and determines the necessary images based on the analysis
      of voxel clusters. We describe a fully automatic plant modeling/phenotyping cell
      (or module) comprising a six-axis robot and a high-precision turntable. By using
      a standard color camera, we overcome the difficulties associated with laser-based
      plant reconstruction methods. The 3D models produced are compared with those
      obtained from fixed cameras and evaluated by comparison with data obtained by x
      ray microcomputed tomography across different plant structures. Our results show
      that our method is successful in improving the accuracy and quality of data
      obtained from a variety of plant types.

PMID- 30097470
TI  - Gunshot Gaza: hospitals struggle to treat surge in firearms injuries.

PMID- 30097469
TI  - An Aromatic Farnesyltransferase Functions in Biosynthesis of the Anti-HIV
      Meroterpenoid Daurichromenic Acid.
AB  - Rhododendron dauricum produces daurichromenic acid, an anti-HIV meroterpenoid,
      via oxidative cyclization of the farnesyl group of grifolic acid. The
      prenyltransferase (PT) that synthesizes grifolic acid is a farnesyltransferase in
      plant specialized metabolism. In this study, we demonstrated that the isoprenoid
      moiety of grifolic acid is derived from the 2-C-methyl-d-erythritol-4-phosphate
      pathway that takes place in plastids. We explored candidate sequences of plastid
      localized PT homologs and identified a cDNA for this PT, RdPT1, which shares
      moderate sequence similarity with known aromatic PTs. RdPT1 is expressed
      exclusively in the glandular scales, where daurichromenic acid accumulates. In
      addition, the gene product was targeted to plastids in plant cells. The
      recombinant RdPT1 regiospecifically synthesized grifolic acid from orsellinic
      acid and farnesyl diphosphate, demonstrating that RdPT1 is the
      farnesyltransferase involved in daurichromenic acid biosynthesis. This enzyme
      strictly preferred orsellinic acid as a prenyl acceptor, whereas it had a relaxed
      specificity for prenyl donor structures, also accepting geranyl and
      geranylgeranyl diphosphates with modest efficiency to synthesize prenyl chain
      analogs of grifolic acid. Such a broad specificity is a unique catalytic feature
      of RdPT1 that is not shared among secondary metabolic aromatic PTs in plants. We
      discuss the unusual substrate preference of RdPT1 using a molecular modeling
      approach. The biochemical properties as well as the localization of RdPT1 suggest
      that this enzyme produces meroterpenoids in glandular scales cooperatively with
      previously identified daurichromenic acid synthase, probably for chemical defense
      on the surface of R. dauricum plants.

PMID- 30097471
TI  - Genomic Signatures of Adaptation to a Precipitation Gradient in Nigerian Sorghum.
AB  - Evolution of plants under climatic gradients may lead to clinal adaptation.
      Understanding the genomic basis of clinal adaptation in crops species could
      facilitate breeding for climate resilience. We investigated signatures of clinal
      adaptation in the cereal crop sorghum (Sorghum bicolor L. [Moench]) to the
      precipitation gradient in West Africa using a panel (n = 607) of sorghum
      accessions from diverse agroclimatic zones of Nigeria. Significant correlations
      were observed between common-garden phenotypes of three putative climate-adaptive
      traits (flowering time, plant height, and panicle length) and climatic variables.
      The panel was characterized at >400,000 single nucleotide polymorphisms (SNPs)
      using genotyping-by-sequencing (GBS). Redundancy analysis indicated that a small
      proportion of SNP variation can be explained by climate (1%), space (1%), and
      climate collinear with space (3%). Discriminant analysis of principal components
      identified three genetic groups that are distributed differently along the
      precipitation gradient. Genome-wide association studies were conducted with
      phenotypes and three climatic variables (annual mean precipitation, precipitation
      in the driest quarter, and annual mean temperature). There was no overall
      enrichment of associations near a priori candidate genes implicated in flowering
      time, height, and inflorescence architecture in cereals, but several significant
      associations were found near a priori candidates including photoperiodic
      flowering regulators SbCN12 and Ma6 Together, the findings suggest that a small
      (3%) but significant proportion of nucleotide variation in Nigerian sorghum
      landraces reflects clinal adaptation along the West African precipitation
      gradient.

PMID- 30097474
TI  - Persistent geotropic positional nystagmus in unilateral cerebellar lesions.
AB  - OBJECTIVE: To determine the prevalence of central lesions in persistent geotropic
      positional nystagmus, and characteristics and anatomical substrates of the
      nystagmus in cerebellar lesions. METHODS: We prospectively recruited 58 patients
      with persistent geotropic positional nystagmus at the Dizziness Clinic of Pusan
      National University Hospital. Seven patients with unilateral cerebellar lesions
      were subjected to analysis of clinical characteristics, oculographic data, and
      MRI lesions. For comparison, we studied 37 cases of peripheral persistent
      geotropic positional nystagmus. RESULTS: The prevalence of central lesions in
      persistent geotropic positional nystagmus was 12% (7/58). Persistent geotropic
      positional nystagmus in cerebellar lesions was mostly asymmetrical. Horizontal
      nystagmus changed in direction during the bow-and-lean test with null positions.
      All patients showed impaired horizontal smooth pursuit bilaterally, and 3 of them
      also had positional downbeat nystagmus. The peak intensity and asymmetry of
      persistent geotropic positional nystagmus did not differ between central and
      peripheral groups (p > 0.05), while there was a difference in the maxima. Lesion
      overlays revealed that damage to the cerebellar tonsil was responsible for the
      generation of persistent geotropic positional nystagmus. CONCLUSION: Although
      persistent geotropic positional nystagmus in cerebellar lesions shares the
      characteristics of nystagmus measures with peripheral cases, accompanying central
      oculomotor signs can aid in differentiation. In tonsillar lesions, compensatory
      rotational feedback due to erroneous estimation of the direction of gravity may
      generate constant horizontal geotropic positional nystagmus.

PMID- 30097473
TI  - Double Selection Enhances the Efficiency of Target-AID and Cas9-Based Genome
      Editing in Yeast.
AB  - CRISPR-Cas9 loss of function (LOF) and base editing screens are powerful tools in
      genetics and genomics. Yeast is one of the main models in these fields, but has
      only recently started to adopt this new toolkit for high throughput experiments.
      We developed a double selection strategy based on co-selection that increases LOF
      mutation rates using the Target-AID base editor. We constructed the pDYSCKO
      vector, which is amenable to high throughput double selection experiments, and
      show that the improvement in Target-AID efficiency generalizes across loci. Using
      modeling, we show that this improvement in efficiency provides the required
      increased in detection power to measure the fitness effects of thousands of
      mutations in typical yeast pooled screens. We show that double selection can also
      improve Cas9 mediated LOF rates, but that this multiplex genome editing causes
      programmable chromosomal translocations at high frequency. This suggests that
      multiplex LOF editing should be performed with caution and that base-editors
      could be preferable tools for some screens in yeast. Base editing using double
      selection is simple and straightforward and provides an alternative to homology
      directed repair based high throughput variant strain construction methods.

PMID- 30097472
TI  - Whole Genome Sequencing, de Novo Assembly and Phenotypic Profiling for the New
      Budding Yeast Species Saccharomyces jurei.
AB  - Saccharomyces sensu stricto complex consist of yeast species, which are not only
      important in the fermentation industry but are also model systems for genomic and
      ecological analysis. Here, we present the complete genome assemblies of
      Saccharomyces jurei, a newly discovered Saccharomyces sensu stricto species from
      high altitude oaks. Phylogenetic and phenotypic analysis revealed that S. jurei
      is more closely related to S. mikatae, than S. cerevisiae, and S. paradoxus The
      karyotype of S. jurei presents two reciprocal chromosomal translocations between
      chromosome VI/VII and I/XIII when compared to the S. cerevisiae genome.
      Interestingly, while the rearrangement I/XIII is unique to S. jurei, the other is
      in common with S. mikatae strain IFO1815, suggesting shared evolutionary history
      of this species after the split between S. cerevisiae and S. mikatae The number
      of Ty elements differed in the new species, with a higher number of Ty elements
      present in S. jurei than in S. cerevisiae Phenotypically, the S. jurei strain
      NCYC 3962 has relatively higher fitness than the other strain NCYC 3947T under
      most of the environmental stress conditions tested and showed remarkably
      increased fitness in higher concentration of acetic acid compared to the other
      sensu stricto species. Both strains were found to be better adapted to lower
      temperatures compared to S. cerevisiae.

PMID- 30097475
TI  - Selective D2 receptor PET in manganese-exposed workers.
AB  - OBJECTIVE: To investigate the associations between manganese (Mn) exposure, D2
      dopamine receptors (D2Rs), and parkinsonism using [11C](N-methyl)benperidol (NMB)
      PET. METHODS: We used NMB PET to evaluate 50 workers with a range of Mn exposure:
      22 Mn-exposed welders, 15 Mn-exposed workers, and 13 nonexposed workers.
      Cumulative Mn exposure was estimated from work histories, and movement disorder
      specialists examined all workers. We calculated NMB D2R nondisplaceable binding
      potential (BPND) for the striatum, globus pallidus, thalamus, and substantia
      nigra (SN). Multivariate analysis of covariance with post hoc descriptive
      discriminate analysis identified regional differences by exposure group. We used
      linear regression to examine the association among Mn exposure, Unified
      Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) score, and regional
      D2R BPND. RESULTS: D2R BPND in the SN had the greatest discriminant power among
      exposure groups (p < 0.01). Age-adjusted SN D2R BPND was 0.073 (95% confidence
      interval [CI] 0.022-0.124) greater in Mn-exposed welders and 0.068 (95% CI 0.013
      0.124) greater in Mn-exposed workers compared to nonexposed workers. After
      adjustment for age, SN D2R BPND was 0.0021 (95% CI 0.0005-0.0042) higher for each
      year of Mn exposure. Each 0.10 increase in SN D2R BPND was associated with a 2.65
      (95% CI 0.56-4.75) increase in UPDRS3 score. CONCLUSIONS AND RELEVANCE: Nigral
      D2R BPND increased with Mn exposure and clinical parkinsonism, indicating dose
      dependent dopaminergic dysfunction of the SN in Mn neurotoxicity.

PMID- 30097476
TI  - Physician-scientists in neurology: Research contributions of a cohort of
      neurologists.
AB  - OBJECTIVE: The objective of this study was to evaluate the methods by which
      neurology physician-scientists are quantified through applying author-level
      metrics to commonly used definitions when discussing funding efforts aimed at the
      attrition of the physician-scientist workforce. METHODS: Neurology residency
      alumni from institutions with the highest National Institute of Neurological
      Disorders and Stroke funding were identified for 2003-2005, and their funding
      records, publishing history, and impact factor (h-index) were obtained via the
      NIH Research Portfolio Online Reporting Tools and Scopus Author Profile. The
      group differences of total publications, yearly publication rate, and h-index
      between R01-funded, non-R01-funded, and nonfunded individuals were analyzed via
      analysis of variance models, and a publications-per-research hour rate was
      calculated and similarly compared across groups. RESULTS: From 15 programs, and
      from a total of 252 neurologists, 186 were identified as having demonstrated an
      interest in research. The mean h-index, yearly publication rate, and cumulative
      number of publications were significantly higher in those who eventually received
      an R01 grant compared to those without R01 funding and those with no research
      funding. Within the top 50 performers by yearly publication rate, there was an
      equal mix of the 3 groups of neurologists: R01 (19, 38%), non-R01 (15, 30%), and
      nonfunded (16, 32%). Those who were nonfunded (10% research effort) had an
      estimated 4.9 publications per 1,000 research hours compared to 3.0 for those
      with non-R01 (40% research effort) funding and 3.2 for those with R01 funding
      (80% research effort). CONCLUSIONS: While eventual R01 grant and early career
      funding pathways were confirmed as important components of higher h-index and
      larger publication numbers, the classic definition of a physician-scientist was
      questioned through these findings. Those presumed to be without funding and
      generally excluded from the physician-scientist pool because of lack of protected
      research time, in some instances, outperformed their R01-funded colleagues and
      had a higher publications-per-research hour than those with an R01 and those with
      non-R01 funding, when estimating a 10% research effort. This reflects a
      potentially erroneous assumption and indicates the important contribution of
      these neurologists.

PMID- 30097478
TI  - The systolic blood pressure sweet spot after intracerebral hemorrhage: 130 mm Hg?

PMID- 30097477
TI  - Nonataxia symptoms in Friedreich Ataxia: Report from the Registry of the European
      Friedreich's Ataxia Consortium for Translational Studies (EFACTS).
AB  - OBJECTIVE: To provide a systematic evaluation of the broad clinical variability
      in Friedreich ataxia (FRDA), a multisystem disorder presenting mainly with
      afferent ataxia but also a complex phenotype of nonataxia symptoms. METHODS: From
      the large database of the European Friedreich's Ataxia Consortium for
      Translational Studies, 650 patients with genetically confirmed FRDA were
      included. Detailed data of medical history documentation, questionnaires, and
      reports on clinical features were analyzed to provide in-depth description of the
      clinical profile and frequency rates of phenotypical features with a focus on
      differences between typical-onset and late-onset FRDA. Logistic regression
      modeling was used to identify predictors for the presence of the most common
      clinical features. RESULTS: The most frequent clinical features beyond afferent
      ataxia were abnormal eye movements (90.5%), scoliosis (73.5%), deformities of the
      feet (58.8%), urinary dysfunction (42.8%), cardiomyopathy and cardiac hypertrophy
      (40.3%), followed by decreased visual acuity (36.8%); less frequent features
      were, among others, depression (14.1%) and diabetes (7.1%). Most of these
      features were more common in the typical-onset group compared to the late-onset
      group. Logistic regression models for the presence of these symptoms demonstrated
      the predictive value of GAA repeat length on the shorter allele and age at onset,
      but also severity of ataxia signs, sex, and presence of neonatal problems.
      CONCLUSIONS: This joint European effort demonstrates the multisystem nature of
      this neurodegenerative disease encompassing most the central nervous,
      neuromuscular, cardiologic, and sensory systems. A distinct and deeper knowledge
      of this rare and chronic disease is highly relevant for clinical practice and
      designs of clinical trials.

PMID- 30097479
TI  - Unintended pregnancy, prenatal care, newborn outcomes, and breastfeeding in women
      with epilepsy.
AB  - OBJECTIVE: To compare the proportions of unintended pregnancies, prenatal vitamin
      or folic acid (PNVF) use, adequate prenatal care visits, and breastfeeding among
      women with epilepsy (WWE) to women without epilepsy (WWoE). METHODS: The
      Pregnancy Risk Assessment Monitoring System (PRAMS) is an annual survey of
      randomly sampled postpartum women administered by the Centers for Disease Control
      and Prevention. We used PRAMS data from 13 states from 2009 to 2014 to compare
      the primary outcomes in WWE and WWoE, as well as our secondary outcomes of
      contraception practices, newborn outcomes, and time to recognition of pregnancy.
      We adjusted for maternal age, race, ethnicity, and socioeconomic status (SES),
      and we calculated odds ratios for these outcomes using logistic regression.
      RESULTS: This analysis included 73,619 women, of whom 541 (0.7%) reported
      epilepsy, representing 3,442,128 WWoE and 26,635 WWE through weighted sampling.
      In WWE, 55% of pregnancies were unintended compared to 48% in WWoE. After
      adjustment for covariates, epilepsy was not associated with unintended pregnancy
      or with inadequate prenatal care. WWE were less likely to report breastfeeding
      but more likely to report daily PNVF use. Newborns of WWE had higher rates of
      prematurity. CONCLUSIONS: Although planning for pregnancy is of utmost importance
      for WWE, more than half the pregnancies in WWE were unintended. Maternal age and
      SES differences likely contribute to the higher rates in WWE compared to WWoE.
      The proportion of women reporting breastfeeding is lower in WWE despite studies
      indicating the safety of breastfeeding in WWE.

PMID- 30097481
TI  - Patch tests should include chemicals used in false nail products, say
      dermatologists.

PMID- 30097480
TI  - Cerebral ischemia and deterioration with lower blood pressure target in
      intracerebral hemorrhage.
AB  - OBJECTIVE: To determine the incidence and predictors of acute cerebral ischemia
      and neurologic deterioration in intracerebral hemorrhage (ICH) patients after an
      institutional protocol change in systolic blood pressure (SBP) target from <160
      to <140 mm Hg. METHODS: We retrospectively compared persons admitted with primary
      ICH before and after a protocol change in SBP target from <160 to <140 mm Hg. The
      primary outcomes were presence of acute cerebral ischemia on MRI completed within
      2 weeks of ICH and acute neurologic deterioration. RESULTS: Of 286 persons with
      primary ICH, 119 underwent MRI and met inclusion criteria. Sixty-two had a target
      SBP <160 mm Hg (group 1) and 57 had a target SBP <140 mm Hg (group 2). There were
      no differences between the 2 groups in baseline clinical and radiographic
      characteristics, but over the first 24 hours of hospitalization, group 2 had
      lower mean SBP (134 vs 143 mm Hg, p < 0.001) and lower minimum SBP over 72 hours
      (106 vs 112 mm Hg, p = 0.02). Acute cerebral ischemia was more frequent in group
      2 than in group 1 (32% vs 16%; p = 0.047) as was acute neurologic deterioration
      (19% vs 5%; p = 0.022). A minimum SBP <=120 mm Hg over 72 hours was associated
      with cerebral ischemia, while no patient with a minimum SBP >=130 mm Hg had
      cerebral ischemia. Acute cerebral ischemia was significantly associated with
      worse discharge NIH Stroke Scale score, while SBP target was not. CONCLUSIONS:
      Intensive lowering of SBP <140 mm Hg in acute ICH, particularly allowing SBP <120
      mm Hg, is associated with increased remote cerebral ischemic lesions and acute
      neurologic deterioration.

PMID- 30097482
TI  - Sex differences in 90-day outcomes after mechanical thrombectomy for acute
      ischemic stroke.
AB  - BACKGROUND: It is largely unknown whether functional outcomes after mechanical
      thrombectomy for large vessel occlusion (LVO) ischemic strokes differ by sex in
      non-clinical trial populations. We investigated sex differences in 90-day
      outcomes among ischemic stroke patients receiving mechanical thrombectomy.
      METHODS: This was a prospective cohort of adults treated with mechanical
      thrombectomy for LVO at a single academic comprehensive stroke center from July
      2015 to April 2017. Data on independence (mRS <=2) at hospital discharge and 90
      days were collected prospectively. Multiple logistic regression was used to
      determine the association between sex and 90-day independence, first adjusting
      for demographics, pre-stroke mRS, and NIHSS, then by co-morbidities and time to
      thrombectomy, and finally by vessel recanalization and use of intravenous
      thrombolysis. RESULTS: We included 279 patients, 52% of whom were female.
      Compared with males, females were older (median years (IQR) 81 (75-88) vs. 71.5
      (60-81), P<0.001) and had higher baseline NIHSS (mean SD 18.2+/-7.5 vs . 16.0+/
      7.1, P=0.02). Similar proportions of males and females had pre-stroke mRS <=2
      (73.3% vs.67.1%, P=0.27). In multivariate analyses, males and females had a
      similar likelihood of being independent at discharge (aOR 0.71 (95%CI 0.32 to
      1.58)), but females were less likely to be independent at 90 days (aOR 0.37 95%
      CI 0.16 to 0.87). CONCLUSIONS: In patients treated with mechanical thrombectomy
      for LVOs at a large comprehensive stroke center, females were less likely to be
      independent at 90 days. Future research should investigate contributors to poor
      outcomes post-discharge in females with LVOs, along with potential interventions
      to improve outcomes.

PMID- 30097483
TI  - Vascular wall components in thrombi obtained by acute stroke thrombectomy:
      clinical significance and related factors.
AB  - BACKGROUND AND PURPOSE: Vascular wall components (VWCs) are sometimes identified
      as collagen fibers in specimens retrieved by thrombectomy from acute stroke
      patients. However, their clinical significance and associated factors remain
      unclear. The purpose of this study was to clarify the factors associated with
      VWCs in retrieved thrombi. METHODS: Consecutive acute stroke patients treated
      endovascularly using the Penumbra aspiration catheter or stent retrievers (SRs)
      at our institute from November 2013 to April 2016 were retrospectively reviewed,
      and the retrieved thrombi were evaluated histopathologically. VWCs were defined
      as banded collagen fibers with a distinct boundary observed at the rim or outside
      of the retrieved thrombi. Factors associated with the presence of VWCs were
      studied. RESULTS: A total of 150 specimens (76 specimens retrieved by the
      Penumbra, 74 by SRs) from 101 patients (47 women, age 74.9+/-11.1 years) were
      investigated. Applied thrombectomy devices were aspiration catheters in 42
      patients, SRs in 21 patients, and both in 38 patients. VWCs were observed in 24
      specimens (16%) from 22 patients. A low proportion of erythrocyte components
      (41.7+/-24.8% vs 55.0+/-26.3%, P=0.01), a high frequency of the devices reaching
      the M2/P2 (75% vs 50%, P=0.02), and a high number of device passages (P for
      trend=0.02) were associated with VWC positive thrombi. Successful recanalization
      (Treatment in Cerebral Ischemia >=2b) tended to be less frequent in patients with
      VWC positive thrombi than in those without (73% vs 89%, P=0.06). CONCLUSIONS: The
      histopathology of occlusive thrombi, arterial sites where devices reached, and
      number of device passages, might affect the presence of VWCs in retrieved
      thrombi.

PMID- 30097484
TI  - NCCT and CTA-based imaging protocol for endovascular treatment selection in late
      presenting or wake-up strokes.
AB  - INTRODUCTION: Recently, the benefit of selecting patients for endovascular
      treatment (EVT) beyond the 6-hour time window using a tissue-based approach was
      demonstrated in two randomized trials. The optimal imaging protocol for selecting
      patients is under debate, and it is still unknown if a simpler and faster
      protocol may adequately select patients with wake-up stroke (WUS) and late
      presenting stroke (LPS) for EVT. OBJECTIVE: To compare outcomes of patients
      submitted to EVT presenting within 6 hours of symptom onset or 6-24 hours after
      last seen well, selected using non-contrast computed tomography (NCCT) and CT
      angiography (CTA). METHODS: An observational study was performed, which included
      consecutive patients with anterior circulation ischemic stroke with large vessel
      occlusion treated with EVT. Patients presenting within 6 hours were treated if
      their NIH Stroke Scale (NIHSS) score was >=6 and Alberta Stroke Program Early CT
      score (ASPECTS) was >=6, while patients presenting with WUS or 6-24 hours after
      last seen well (WUS/LPS) were treated if their NIHSSscore was >=12 and ASPECTS
      was >=7. RESULTS: 249 patients were included, 63 of whom were in the WUS/LPS
      group. Baseline characteristics were similar between groups, except for longer
      symptom-recanalization time, lower admission NIHSS (16 vs 17, P=0.038), more
      frequent tandem occlusions (25.4% vs 11.8%, P=0.010), and large artery
      atherosclerosis etiology (22.2% vs 11.8%, P=0.043) in the WUS/LPS group. No
      differences in symptomatic intracranial hemorrhage, peri-procedural complications
      or mortality were found between groups. Three-month functional independence was
      similar in both groups (65.1% in WUS/LPS vs 57.0% in <=6 hours, P=0.259) and no
      differences were found after adjustment for confounders. CONCLUSIONS: This real
      world observational study suggests that EVT may be safe and effective in patients
      with WUS and LPS selected using clinical-core mismatch (high NIHSS/high ASPECTS
      in NCCT).

PMID- 30097486
TI  - iRGD-guided Tumor-penetrating Nanocomplexes for Therapeutic siRNA Delivery to
      Pancreatic Cancer.
AB  - Pancreatic cancer is one of the leading causes of cancer-related death, with 5
      year survival of 8.5%. The lack of significant progress in improving therapy
      reflects our inability to overcome the desmoplastic stromal barrier in pancreatic
      ductal adenocarcinoma (PDAC) as well as a paucity of new approaches targeting its
      genetic underpinnings. RNA interference holds promise in targeting key mutations
      driving PDAC; however, a nucleic acid delivery vehicle that homes to PDAC and
      breaches the stroma does not yet exist. Noting that the cyclic peptide iRGD
      mediates tumor targeting and penetration through interactions with alphavbeta3/5
      integrins and neuropilin-1, we hypothesized that "tandem" peptides combining a
      cell-penetrating peptide and iRGD can encapsulate siRNA to form tumor-penetrating
      nanocomplexes (TPN) capable of delivering siRNA to PDAC. The use of directly
      conjugated iRGD is justified by receptor expression patterns in human PDAC
      biopsies. In this work, we optimize iRGD TPNs with polyethylene glycol (PEG)
      peptide conjugates for systemic delivery to sites of disease. We show that TPNs
      effectively knockdown siRNA targets in PDAC cell lines and in an immunocompetent
      genetically engineered mouse model of PDAC. Furthermore, we validate their tumor
      penetrating ability in three-dimensional organoids and autochthonous tumors. In
      murine therapeutic trials, TPNs delivering anti-Kras siRNA significantly delay
      tumor growth. Thus, iRGD TPNs hold promise in treating PDAC by not only
      overcoming physical barriers to therapy, but by leveraging the stroma to achieve
      knockdown of the gold-standard genetic target. Moreover, the modular construction
      of this delivery platform allows for facile adaptation to future genetic target
      candidates in pancreatic cancer. Mol Cancer Ther; 17(11); 2377-88. (c)2018 AACR.

PMID- 30097487
TI  - Improving Efficacy and Safety of Agonistic Anti-CD40 Antibody Through
      Extracellular Matrix Affinity.
AB  - CD40 is an immune costimulatory receptor expressed by antigen-presenting cells.
      Agonistic anti-CD40 antibodies have demonstrated considerable antitumor effects
      yet can also elicit serious treatment-related adverse events, such as liver
      toxicity, including in man. We engineered a variant that binds extracellular
      matrix through a super-affinity peptide derived from placenta growth factor-2
      (PlGF-2123-144) to enhance anti-CD40's effects when administered locally.
      Peritumoral injection of PlGF-2123-144-anti-CD40 antibody showed prolonged tissue
      retention at the injection site and substantially decreased systemic exposure,
      resulting in decreased liver toxicity. In four mouse tumor models, PlGF-2123-144
      anti-CD40 antibody demonstrated enhanced antitumor efficacy compared with its
      unmodified form and correlated with activated dendritic cells, B cells, and T
      cells in the tumor and in the tumor-draining lymph node. Moreover, in a
      genetically engineered BrafV600E betaCatSTA melanoma model that does not respond
      to checkpoint inhibitors, PlGF-2123-144-anti-CD40 antibody treatment enhanced T
      cell infiltration into the tumors and slowed tumor growth. Together, these
      results demonstrate the marked therapeutic advantages of engineering matrix
      binding domains onto agonistic anti-CD40 antibody as a therapeutic given by
      tumori-regional injection for cancer immunotherapy.Implications: Extracellular
      matrix-binding peptide conjugation to agonistic anti-CD40 antibody enhances
      antitumor efficacy and reduces treatment-related adverse events. Mol Cancer Ther;
      17(11); 2399-411. (c)2018 AACR.

PMID- 30097488
TI  - Noninvasive Detection of ctDNA Reveals Intratumor Heterogeneity and Is Associated
      with Tumor Burden in Gastrointestinal Stromal Tumor.
AB  - Molecular analysis of circulating tumor DNA (ctDNA) has a large potential for
      clinical application by capturing tumor-specific aberrations through noninvasive
      sampling. In gastrointestinal stromal tumor (GIST), analysis of KIT and PDGFRA
      mutations is important for therapeutic decisions, but the invasiveness of
      traditional biopsies limits the possibilities for repeated sampling. Using
      targeted next-generation sequencing, we have analyzed circulating cell-free DNA
      from 50 GIST patients. Tumor-specific mutations were detected in 16 of 44 plasma
      samples (36%) from treatment-naive patients and in three of six (50%) patients
      treated with tyrosine kinase inhibitors. A significant association between
      detection of ctDNA and the modified National Institutes of Health risk
      classification was found. All patients with metastatic disease had detectable
      ctDNA, and tumor burden was the most important detection determinant. Median
      tumor size was 13.4 cm for patients with detectable mutation in plasma compared
      with 4.4 cm in patients without detectable mutation (P = 0.006). ctDNA analysis
      of a patient with disease progression on imatinib revealed that multiple
      resistance mutations were synchronously present, and detailed analysis of tumor
      tissue showed that these were spatially distributed in the primary tumor. Plasma
      samples taken throughout the course of treatment demonstrated that clonal
      evolution can be monitored over time. In conclusion, we have shown that detection
      of GIST-specific mutations in plasma is particularly feasible for patients with
      high tumor burden. In such cases, we have demonstrated that mutational analysis
      by use of liquid biopsies can capture the molecular heterogeneity of the whole
      tumor, and may guide treatment decisions during progression. Mol Cancer Ther;
      17(11); 2473-80. (c)2018 AACR.

PMID- 30097489
TI  - Combined Inhibition of PI3Kbeta and mTOR Inhibits Growth of PTEN-null Tumors.
AB  - Loss of the tumor suppressor PTEN confers a tumor cell dependency on the PI3Kbeta
      isoform. Achieving maximal inhibition of tumor growth through PI3K pathway
      inhibition requires sustained inhibition of PI3K signaling; however, efficacy is
      often limited by suboptimal inhibition or reactivation of the pathway. To select
      combinations that deliver comprehensive suppression of PI3K signaling in PTEN
      null tumors, the PI3Kbeta inhibitor AZD8186 was combined with inhibitors of
      kinases implicated in pathway reactivation in an extended cell proliferation
      assay. Inhibiting PI3Kbeta and mTOR gave the most effective antiproliferative
      effects across a panel of PTEN-null tumor cell lines. The combination of AZD8186
      and the mTOR inhibitor vistusertib was also effective in vivo controlling growth
      of PTEN-null tumor models of TNBC, prostate, and renal cancers. In vitro, the
      combination resulted in increased suppression of pNDRG1, p4EBP1, as well as
      HMGCS1 with reduced pNDRG1 and p4EBP1 more closely associated with effective
      suppression of proliferation. In vivo biomarker analysis revealed that the
      monotherapy and combination treatment consistently reduced similar biomarkers,
      while combination increased nuclear translocation of the transcription factor
      FOXO3 and reduction in glucose uptake. These data suggest that combining the
      PI3Kbeta inhibitor AZD8186 and vistusertib has potential to be an effective
      combination treatment for PTEN-null tumors. Mol Cancer Ther; 17(11); 2309-19.
      (c)2018 AACR.

PMID- 30097490
TI  - Value of hospital resources for effective pressure injury prevention: a cost
      effectiveness analysis.
AB  - OBJECTIVE: Hospital-acquired pressure injuries are localised skin injuries that
      cause significant mortality and are costly. Nursing best practices prevent
      pressure injuries, including time-consuming, complex tasks that lack payment
      incentives. The Braden Scale is an evidence-based stratification tool nurses use
      daily to assess pressure-injury risk. Our objective was to analyse the cost
      utility of performing repeated risk-assessment for pressure-injury prevention in
      all patients or high-risk groups. DESIGN: Cost-utility analysis using Markov
      modelling from US societal and healthcare sector perspectives within a 1-year
      time horizon. SETTING: Patient-level longitudinal data on 34 787 encounters from
      an academic hospital electronic health record (EHR) between 2011 and 2014,
      including daily Braden scores. Supervised machine learning simulated age-adjusted
      transition probabilities between risk levels and pressure injuries. PARTICIPANTS:
      Hospitalised adults with Braden scores classified into five risk levels: very
      high risk (6-9), high risk (10-11), moderate risk (12-14), at-risk (15-18),
      minimal risk (19-23). INTERVENTIONS: Standard care, repeated risk assessment in
      all risk levels or only repeated risk assessment in high-risk strata based on
      machine-learning simulations. MAIN OUTCOME MEASURES: Costs (2016 $US) of pressure
      injury treatment and prevention, and quality-adjusted life years (QALYs) related
      to pressure injuries were weighted by transition probabilities to calculate the
      incremental cost-effectiveness ratio (ICER) at $100 000/QALY willingness-to-pay.
      Univariate and probabilistic sensitivity analyses tested model uncertainty.
      RESULTS: Simulating prevention for all patients yielded greater QALYs at higher
      cost from societal and healthcare sector perspectives, equating to ICERs of
      $2000/QALY and $2142/QALY, respectively. Risk-stratified follow-up in patients
      with Braden scores <15 dominated standard care. Prevention for all patients was
      cost-effective in >99% of probabilistic simulations. CONCLUSION: Our analysis
      using EHR data maintains that pressure-injury prevention for all inpatients is
      cost-effective. Hospitals should invest in nursing compliance with international
      prevention guidelines.

PMID- 30097491
TI  - Revitalising the GP partnership model.

PMID- 30097492
TI  - Preconditioning c-Kit-positive human cardiac stem cells with a nitric oxide donor
      enhances cell survival through activation of survival signaling pathways.

PMID- 30097493
TI  - An exTREMe disruption in Alzheimer's cleanup.
AB  - Partial loss-of-function variants in the TREM2 immune receptor are associated
      with increased risk for Alzheimer's disease (AD) and other forms of
      neurodegenerative disease, but the molecular bases for these connections are
      unknown. Three new structures of WT and R47H mutant TREM2 immunoglobulin-like (Ig
      like) domain now reveal that R47 functions to correctly position elements of the
      ligand-binding surface. Intriguingly, the authors also demonstrate a disruption
      of receptor oligomerization by the R47H mutation, suggesting a role for ligand
      induced clustering in receptor signaling and resultant plaque clearance.

PMID- 30097494
TI  - Quantifying intracellular rates of glycolytic and oxidative ATP production and
      consumption using extracellular flux measurements.

PMID- 30097495
TI  - Learning in the 21st Century: Concepts and Tools.

PMID- 30097496
TI  - Direct Comparison of Cardiac Troponin T and I Using a Uniform and a Sex-Specific
      Approach in the Detection of Functionally Relevant Coronary Artery Disease.
AB  - BACKGROUND: We aimed to directly compare high-sensitivity cardiac troponin I (hs
      cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) in the detection of
      functionally relevant coronary artery disease (fCAD). METHODS: Consecutive
      patients referred with clinical suspicion of fCAD and no structural heart disease
      other than coronary artery disease were included. The presence of fCAD was based
      on rest/stress myocardial perfusion single-photon emission computed
      tomography/computed tomography and coronary angiography. hs-cTnI and hs-cTnT
      concentrations were measured in a blinded fashion. Diagnostic accuracy was
      quantified using the area under the ROC curve (AUC) and evaluated both for
      uniform use in all patients and for sex-specific use in women and men separately.
      The prognostic end point was major adverse cardiac events (MACEs; cardiovascular
      death or myocardial infarction) within 2 years. For the prognostic performance,
      we used a multivariable model comparison with the Akaike information criterion
      (AIC). RESULTS: fCAD was detected in 613 of 2062 patients (29.7%) overall, 112 of
      664 of women (16.9%), and 501 of 1398 of men (35.8%). hs-cTnI and hs-cTnT had
      comparable diagnostic accuracy when assessed for uniform use in all patients
      (AUC, 0.68 vs 0.66; P = 0.107) and separately in women (AUC, 0.68 vs 0.63; P =
      0.068) and men (AUC, 0.65 vs 0.64; P = 0.475). However, women required lower rule
      out cutoffs to achieve high sensitivity, and men needed higher rule-in cutoffs to
      achieve high specificity. hs-cTnI and hs-cTnT were strongly and independently
      associated with MACE within 2 years (P < 0.001), with comparable prognostic
      accuracies by the AIC. CONCLUSIONS: hs-cTnI and hs-cTnT provide moderate and
      comparable diagnostic accuracy. Sex-specific cutoffs may be preferred. The
      prognostic utility of both troponins is comparable.

PMID- 30097497
TI  - Discovery and Validation of Salivary Extracellular RNA Biomarkers for Noninvasive
      Detection of Gastric Cancer.
AB  - BACKGROUND: Biomarkers are needed for noninvasive early detection of gastric
      cancer (GC). We investigated salivary extracellular RNA (exRNA) biomarkers as
      potential clinical evaluation tools for GC. METHODS: Unstimulated whole saliva
      samples were prospectively collected from 294 individuals (163 GC and 131 non-GC
      patients) who underwent endoscopic evaluation at the Samsung Medical Center in
      Korea. Salivary transcriptomes of 63 GC and 31 non-GC patients were profiled, and
      mRNA biomarker candidates were verified with reverse transcription quantitative
      real-time PCR (RT-qPCR). In parallel, microRNA (miRNA) biomarkers were profiled
      and verified with saliva samples from 10 GC and 10 non-GC patients. Candidate
      biomarkers were validated with RT-qPCR in an independent cohort of 100/100 saliva
      samples from GC and non-GC patients. Validated individual markers were configured
      into a best performance panel. RESULTS: We identified 30 mRNA and 15 miRNA
      candidates whose expression pattern associated with the presence of GC. Among
      them, 12 mRNA and 6 miRNA candidates were verified with the discovery cohort by
      RT-qPCR and further validated with the independent cohort (n = 200). The
      configured biomarker panel consisted of 3 mRNAs (SPINK7, PPL, and SEMA4B) and 2
      miRNAs (MIR140-5p and MIR301a), which were all significantly down-regulated in
      the GC group, and yielded an area under the ROC curve (AUC) of 0.81 (95% CI, 0.72
      0.89). When combined with demographic factors, the AUC of the biomarker panel
      reached 0.87 (95% CI, 0.80-0.93). CONCLUSIONS: We have discovered and validated a
      panel of salivary exRNA biomarkers with credible clinical performance for the
      detection of GC. Our study demonstrates the potential utility of salivary exRNA
      biomarkers in screening and risk assessment for GC.

PMID- 30097498
TI  - Biochemical Diagnosis of Chromaffin Cell Tumors in Patients at High and Low Risk
      of Disease: Plasma versus Urinary Free or Deconjugated O-Methylated Catecholamine
      Metabolites.
AB  - BACKGROUND: Measurements of plasma or urinary metanephrines are recommended for
      diagnosis of pheochromocytoma and paraganglioma (PPGL). What test offers optimal
      diagnostic accuracy for patients at high and low risk of disease, whether urinary
      free metanephrines offer advantages over deconjugated metanephrines, and what
      advantages are offered by including methoxytyramine in panels all remain unclear.
      METHODS: A population of 2056 patients with suspected PPGLs underwent prospective
      screening for disease using mass spectrometric-based measurements of plasma free,
      urinary deconjugated, and urinary free metanephrines and methoxytyramine. PPGLs
      were confirmed in 236 patients and were excluded in others on follow-up
      evaluation. RESULTS: Measurements of plasma free metabolites offered higher (P <
      0.01) diagnostic sensitivity (97.9%) than urinary free (93.4%) and deconjugated
      (92.9%) metabolites at identical specificities for plasma and urinary free
      metabolites (94.2%) but at a lower (P < 0.005) specificity for deconjugated
      metabolites (92.1%). The addition of methoxytyramine offered little value for
      urinary panels but provided higher (P < 0.005) diagnostic performance for plasma
      measurements than either urinary panel according to areas under ROC curves (0.991
      vs 0.972 and 0.964). Diagnostic performance of urinary and plasma tests was
      similar for patients at low risk of disease, whereas plasma measurements were
      superior to both urinary panels for high-risk patients. CONCLUSIONS: Diagnosis of
      PPGLs using plasma or urinary free metabolites provides advantages of fewer false
      positive results compared with commonly measured deconjugated metabolites. The
      plasma panel offers better diagnostic performance than either urinary panel for
      patients at high risk of disease and, with appropriate preanalytics, provides the
      test of choice. Measurements of methoxytyramine in urine show limited diagnostic
      utility compared with plasma.

PMID- 30097499
TI  - Using Machine Learning to Aid the Interpretation of Urine Steroid Profiles.
AB  - BACKGROUND: Urine steroid profiles are used in clinical practice for the
      diagnosis and monitoring of disorders of steroidogenesis and adrenal pathologies.
      Machine learning (ML) algorithms are powerful computational tools used
      extensively for the recognition of patterns in large data sets. Here, we
      investigated the utility of various ML algorithms for the automated biochemical
      interpretation of urine steroid profiles to support current clinical practices.
      METHODS: Data from 4619 urine steroid profiles processed between June 2012 and
      October 2016 were retrospectively collected. Of these, 1314 profiles were used to
      train and test various ML classifiers' abilities to differentiate between "No
      significant abnormality" and "?Abnormal" profiles. Further classifiers were
      trained and tested for their ability to predict the specific biochemical
      interpretation of the profiles. RESULTS: The best performing binary classifier
      could predict the interpretation of No significant abnormality and ?Abnormal
      profiles with a mean area under the ROC curve of 0.955 (95% CI, 0.949-0.961). In
      addition, the best performing multiclass classifier could predict the individual
      abnormal profile interpretation with a mean balanced accuracy of 0.873 (0.865
      0.880). CONCLUSIONS: Here we have described the application of ML algorithms to
      the automated interpretation of urine steroid profiles. This provides a proof-of
      concept application of ML algorithms to complex clinical laboratory data that has
      the potential to improve laboratory efficiency in a setting of limited staff
      resources.

PMID- 30097500
TI  - Type 1 diabetes: earlier onset is linked to cardiovascular complications and
      reduced lifespan.

PMID- 30097501
TI  - Risk stratification of thyroid nodules using Thyroid Imaging Reporting And Data
      System (TIRADS): The omission of thyroid scintigraphy increases the rate of
      falsely suspected lesions.
AB  - Background: Thyroid nodules are a common finding, especially in iodine-deficient
      regions. Ultrasonographic scoring systems such as Thyroid Imaging Reporting And
      Data System (TIRADS) are helpful in differentiating between benign and malignant
      thyroid nodules by offering a risk stratification model. Depending on the
      constellation or number of suspicious ultrasound features, a fine needle biopsy
      (FNB) is recommended. However, none of the previously published TIRADS considered
      the functional status of the nodules. Hyperfunctioning thyroid nodules (HTN) were
      presumed to exclude malignancy with a very high negative predictive value.
      Particularly in regions where the iodine supply is lower, the majority of HTN are
      seen in patients with normal TSH levels. Therefore, thyroid scintigraphy is
      essential for the detection of HTN. We investigated whether TIRADS identifies HTN
      as non-suspicious. Methods: We evaluated 615 HTN (23.2+/-10.0 mm at maximum
      diameter in 582 patients (n = 442 female, 57.7+/-13.2 years, and n = 140 male,
      60.1 +/-12.7 years) detected by 99mTc Pertechnetate or 123Iodine scintigraphy.
      Prior to evaluating the scintigraphic appearance, all nodules were analyzed
      prospectively with sonography, using the TIRADS model referenced in Kwak et al.,
      wherein fine needle biopsy is recommended for TIRADS 4A or higher. We also
      investigated two subgroups, 42 nodules with available histology as well as 117
      patients with subclinical or overt hyperthyroidism. Results: Whereas 15.9% of the
      nodules were classified as TIRADS 3 or lower and <0.1% as TIRADS 5, most of the
      nodules were classified as TIRADS 4A (29.3%), 4B (29.3%), and 4C (24.9%),
      respectively. Altogether, more than 80% of the autonomous thyroid nodules were
      classified as TIRADS 4A or higher which would result in a recommendation of fine
      needle biopsy. Focusing on those 117 HTN that were already associated with
      hyperthyroid laboratory values, the rates were similar: 81.2% were categorized as
      TIRADS 4A or higher (4A: 33.3%, 4B: 29.9%, 4C:17.1%, 5: 0.9%). In the subgroup of
      patients who underwent thyroid surgery, all nodules were benign, confirming the
      known NPV of HTN with regard to malignancy exclusion. Conclusion: Integration of
      thyroid scintigraphy into the TIRADS model is essential to prevent unnecessary
      FNB and thyroid surgery.

PMID- 30097502
TI  - Assessment of the Right-to-Try Law: The Pros and the Cons.

PMID- 30097504
TI  - Fibroblast-Activating Protein: Targeting the Roots of the Tumor Microenvironment.

PMID- 30097503
TI  - Monosodium Glutamate Reduces 68Ga-PSMA-11 Uptake in Salivary Glands and Kidneys
      in a Preclinical Prostate Cancer Model.
AB  - We evaluated the ability of monosodium glutamate (MSG) to reduce salivary and
      kidney uptake of a prostate-specific membrane antigen (PSMA) radioligand without
      affecting tumor uptake. Methods: LNCaP tumor-bearing mice were intraperitoneally
      injected with MSG (657, 329, or 164 mg/kg) or phosphate-buffered saline (PBS).
      Fifteen minutes later, the mice were intravenously administered 68Ga-PSMA-11.
      PET/CT imaging and biodistribution studies were performed 1 h after
      administration. Results: Tumor uptake (percentage injected dose per gram [%ID])
      was not statistically different between groups, at 8.42 +/- 1.40 %ID in the 657
      mg/kg group, 7.19 +/- 0.86 %ID in the 329 mg/kg group, 8.20 +/- 2.44 %ID in the
      164 mg/kg group, and 8.67 +/- 1.97 %ID in the PBS group. Kidney uptake was
      significantly lower in the 657 mg/kg group (85.8 +/- 24.2 %ID) than in the 329
      mg/kg (159 +/- 26.2 %ID), 164 mg/kg (211 +/- 27.4 %ID), and PBS groups (182 +/-
      33.5 %ID) (P < 0.001). Salivary gland uptake was lower in the 657 mg/kg (3.72 +/-
      2.12 %ID) and 329 mg/kg (5.74 +/- 0.62 %ID) groups than in the PBS group (10.04
      +/- 2.52 %ID) (P < 0.01). Conclusion: MSG decreased salivary and kidney uptake of
      68Ga-PSMA-11 in a dose-dependent manner, whereas tumor uptake was unaffected.

PMID- 30097506
TI  - Radiation Dose Does Indeed Matter: Proof That Invalidates The Linear No-Threshold
      Model.

PMID- 30097505
TI  - Evaluation of 18F-RO-948 PET for Quantitative Assessment of Tau Accumulation in
      the Human Brain.
AB  - The availability of tau PET radioligands enables quantitative assessment of tau
      density and distribution in the human brain. We evaluated the kinetics of a novel
      radioligand, 18F-RO-948 (previously referred to as 18F-RO6958948), and its
      ability to identify tau positivity in individual patients with mild Alzheimer
      disease (AD). Methods: Eleven subjects with amyloid-positive mild AD, 5 amyloid
      negative older control subjects (OC), and 5 younger control subjects (YC)
      completed 1 or 2 (4 AD and 5 OC) PET scans with 18F-RO-948 for 90, 120, or 200
      min. The kinetics of the radioligand was evaluated with standard compartmental
      and noncompartmental models (with plasma data in 70% of cases), tissue-reference
      methods, and SUV ratio. These approaches were applied to assess the ability of
      18F-RO-948 to discriminate AD subjects from OC subjects. Results: The plasma
      reference graphical analysis appeared to be the optimal method of quantification
      for 18F-RO-948, yielding strictly time-consistent values of distribution volume
      and distribution volume ratio at 90 min against the analyses at 120 and 200 min.
      The reference tissue graphical analysis and SUV ratio were cross-validated
      against plasma reference graphical analysis. Test-retest evaluation showed
      excellent reproducibility. A proposed novel index of tau load, the regional tau
      positive fraction, showed high values in the medial and lateral temporal and
      parietal regions in AD and successfully separated AD subjects from OC and YC
      subjects with a significant margin. Conclusion: 18F-RO-948 appears to be a
      promising radioligand for quantitative imaging of tau in the brain of AD
      patients.

PMID- 30097508
TI  - Attenuated arsenic trioxide plus ATRA therapy for newly diagnosed and relapsed
      APL: long-term follow-up of the AML17 trial.

PMID- 30097509
TI  - Erythroferrone inhibits the induction of hepcidin by BMP6.
AB  - Decreased hepcidin mobilizes iron, which facilitates erythropoiesis, but excess
      iron is pathogenic in beta-thalassemia. Erythropoietin (EPO) enhances
      erythroferrone (ERFE) synthesis by erythroblasts, and ERFE suppresses hepatic
      hepcidin production through an unknown mechanism. The BMP/SMAD pathway in the
      liver is critical for hepcidin control, and we show that EPO suppressed hepcidin
      and other BMP target genes in vivo in a partially ERFE-dependent manner.
      Furthermore, recombinant ERFE suppressed the hepatic BMP/SMAD pathway
      independently of changes in serum and liver iron. In vitro, ERFE decreased SMAD1,
      SMAD5, and SMAD8 phosphorylation and inhibited expression of BMP target genes.
      ERFE specifically abrogated the induction of hepcidin by BMP5, BMP6, and BMP7 but
      had little or no effect on hepcidin induction by BMP2, BMP4, BMP9, or activin B.
      A neutralizing anti-ERFE antibody prevented ERFE from inhibiting hepcidin
      induction by BMP5, BMP6, and BMP7. Cell-free homogeneous time-resolved
      fluorescence assays showed that BMP5, BMP6, and BMP7 competed with anti-ERFE for
      binding to ERFE. We conclude that ERFE suppresses hepcidin by inhibiting hepatic
      BMP/SMAD signaling via preferentially impairing an evolutionarily closely related
      BMP subgroup of BMP5, BMP6, and BMP7. ERFE can act as a natural ligand trap
      generated by stimulated erythropoiesis to regulate the availability of iron.

PMID- 30097510
TI  - E-cigarette users commonly stealth vape in places where e-cigarette use is
      prohibited.
AB  - INTRODUCTION: 'Stealth vaping' is the practice of vaping discreetly in places
      where electronic cigarette (e-cigarette) use is prohibited. While anecdotal
      evidence suggests that stealth vaping is common, there have been no formal
      studies of the behaviour. The purpose of this study is to examine stealth vaping
      behaviour among experienced e-cigarette users. METHODS: Data were collected from
      the follow-up survey of a large longitudinal cohort study of adult experienced e
      cigarette users conducted in January 2017. To measure stealth vaping behaviour,
      participants were asked 'Have you ever 'stealth vaped', that is to say, used an e
      cig in a public place where it was not approved and attempted to conceal your e
      cig use? (yes/no)'. Participants indicating yes completed additional questions
      about the frequency of stealth vaping and were asked to select all the locations
      where they commonly stealth vape. Frequencies were used to examine the overall
      prevalence, frequency and common locations for stealth vaping. A logistic
      regression model was run to predict stealth vaping. RESULTS: Approximately two
      thirds (64.3%, n=297/462) of the sample reported ever stealth vaping, of which
      52.5% (n=156/297) reported stealth vaping in the past week. Among stealth vapers
      (n=297), 31% reported owning a smaller device solely for stealth vaping. The most
      common places to stealth vape included at work (46.8%), followed by
      bars/nightclubs (42.1%), restaurants (37.7%), at the movies (35.4%) and in
      airports/on airplanes (11.7%). Predictors of stealth vaping were greater
      dependence and owning a smaller device solely for stealth vaping. CONCLUSIONS:
      Stealth vaping is a common behaviour for many experienced e-cigarette users. More
      research is needed to understand the reasons for stealth vaping and its potential
      health and safety implications. This information could help researchers and
      regulators to design interventions to minimise the public health impact of
      stealth vaping.

PMID- 30097511
TI  - Determinants of body fat distribution in humans may provide insight about obesity
      related health risks.
AB  - Obesity increases the risks of developing cardiovascular and metabolic diseases
      and degrades quality of life, ultimately increasing the risk of death. However,
      not all forms of obesity are equally dangerous: some individuals, despite higher
      percentages of body fat, are at less risk for certain chronic obesity-related
      complications. Many open questions remain about why this occurs. Data suggest
      that the physical location of fat and the overall health of fat dramatically
      influence disease risk; for example, higher concentrations of visceral relative
      to subcutaneous adipose tissue are associated with greater metabolic risks. As
      such, understanding the determinants of the location and health of adipose tissue
      can provide insight about the pathological consequences of obesity and can begin
      to outline targets for novel therapeutic approaches to combat the obesity
      epidemic. Although age and sex hormones clearly play roles in fat distribution
      and location, much remains unknown about gene regulation at the level of adipose
      tissue or how genetic variants regulate fat distribution. In this review, we
      discuss what is known about the determinants of body fat distribution, and we
      highlight the important roles of sex hormones, aging, and genetic variation in
      the determination of body fat distribution and its contribution to obesity
      related comorbidities.

PMID- 30097512
TI  - Correction: European League Against Rheumatism/American College of Rheumatology
      classification criteria for adult and juvenile idiopathic inflammatory myopathies
      and their major subgroups.

PMID- 30097507
TI  - Comparative proteomics reveals a diagnostic signature for pulmonary head-and-neck
      cancer metastasis.
AB  - Patients with head-and-neck cancer can develop both lung metastasis and primary
      lung cancer during the course of their disease. Despite the clinical importance
      of discrimination, reliable diagnostic biomarkers are still lacking. Here, we
      have characterised a cohort of squamous cell lung (SQCLC) and head-and-neck
      (HNSCC) carcinomas by quantitative proteomics. In a training cohort, we
      quantified 4,957 proteins in 44 SQCLC and 30 HNSCC tumours. A total of 518
      proteins were found to be differentially expressed between SQCLC and HNSCC, and
      some of these were identified as genetic dependencies in either of the two tumour
      types. Using supervised machine learning, we inferred a proteomic signature for
      the classification of squamous cell carcinomas as either SQCLC or HNSCC, with
      diagnostic accuracies of 90.5% and 86.8% in cross- and independent validations,
      respectively. Furthermore, application of this signature to a cohort of pulmonary
      squamous cell carcinomas of unknown origin leads to a significant prognostic
      separation. This study not only provides a diagnostic proteomic signature for
      classification of secondary lung tumours in HNSCC patients, but also represents a
      proteomic resource for HNSCC and SQCLC.

PMID- 30097513
TI  - Cyclin B2 can compensate for Cyclin B1 in oocyte meiosis I.
AB  - Mammalian oocytes are arrested at the prophase of the first meiotic division for
      months and even years, depending on species. Meiotic resumption of fully grown
      oocytes requires activation of M-phase-promoting factor (MPF), which is composed
      of Cyclin B1 and cyclin-dependent kinase 1 (CDK1). It has long been believed that
      Cyclin B1 synthesis/accumulation and its interaction with CDK1 is a prerequisite
      for MPF activation in oocytes. In this study, we revealed that oocyte meiotic
      resumption occurred in the absence of Cyclin B1. Ccnb1-null oocytes resumed
      meiosis and extruded the first polar body. Without Cyclin B1, CDK1 could be
      activated by up-regulated Cyclin B2. Ccnb1 and Ccnb2 double knockout permanently
      arrested the oocytes at the prophase of the first meiotic division. Oocyte
      specific Ccnb1-null female mice were infertile due to failed MPF activity
      elevation and thus premature interphase-like stage entry in the second meiotic
      division. These results have revealed a hidden compensatory mechanism between
      Cyclin B1 and Cyclin B2 in regulating MPF and oocyte meiotic resumption.

PMID- 30097514
TI  - Reconstitution reveals Ykt6 as the autophagosomal SNARE in autophagosome-vacuole
      fusion.
AB  - Autophagy mediates the bulk degradation of cytoplasmic material, particularly
      during starvation. Upon the induction of autophagy, autophagosomes form a sealed
      membrane around cargo, fuse with a lytic compartment, and release the cargo for
      degradation. The mechanism of autophagosome-vacuole fusion is poorly understood,
      although factors that mediate other cellular fusion events have been implicated.
      In this study, we developed an in vitro reconstitution assay that enables
      systematic discovery and dissection of the players involved in autophagosome
      vacuole fusion. We found that this process requires the Atg14-Vps34 complex to
      generate PI3P and thus recruit the Ypt7 module to autophagosomes. The HOPS
      tethering complex, recruited by Ypt7, is required to prepare SNARE proteins for
      fusion. Furthermore, we discovered that fusion requires the R-SNARE Ykt6 on the
      autophagosome, together with the Q-SNAREs Vam3, Vam7, and Vti1 on the vacuole.
      These findings shed new light on the mechanism of autophagosome-vacuole fusion
      and reveal that the R-SNARE Ykt6 is required for this process.

PMID- 30097515
TI  - A novel in vitro assay reveals SNARE topology and the role of Ykt6 in
      autophagosome fusion with vacuoles.
AB  - Autophagy is a catabolic pathway that delivers intracellular material to the
      mammalian lysosomes or the yeast and plant vacuoles. The final step in this
      process is the fusion of autophagosomes with vacuoles, which requires SNARE
      proteins, the homotypic vacuole fusion and protein sorting tethering complex, the
      RAB7-like Ypt7 GTPase, and its guanine nucleotide exchange factor, Mon1-Ccz1.
      Where these different components are located and function during fusion, however,
      remains to be fully understood. Here, we present a novel in vitro assay to
      monitor fusion of intact and functional autophagosomes with vacuoles. This
      process requires ATP, physiological temperature, and the entire fusion machinery
      to tether and fuse autophagosomes with vacuoles. Importantly, we uncover Ykt6 as
      the autophagosomal SNARE. Our assay and findings thus provide the tools to
      dissect autophagosome completion and fusion in a test tube.

PMID- 30097516
TI  - The homeobox transcription factor MSX2 partially mediates the effects of bone
      morphogenetic protein 4 (BMP4) on somatic cell reprogramming.
AB  - Bone morphogenetic proteins (BMPs) induce mesenchymal-epithelial transition (MET)
      and enhance the generation of induced pluripotent stem cells (iPSCs). However,
      BMPs are also signaling molecules critical for arresting reprogramming in the pre
      iPSC state. In this study, using mouse embryonic fibroblasts, we found that the
      time- and concentration-dependent effects of BMPs on reprogramming are mediated
      by Msh homeobox 2 (MSX2), a homeobox-containing transcription factor. BMPs up
      regulated Msx2 by activating SMAD1/5, and MSX2 then directly bound to the
      promoters and up-regulated the expression of the cadherin 1 (Cdh1, also known as
      E-cadherin), GATA-binding protein 3 (Gata3), and Nanog genes. Cdh1 contributed to
      BMP4- and MSX2-induced MET and subsequently promoted reprogramming. On the other
      hand, GATA3 promoted reprogramming, possibly by up-regulating Spalt-like
      transcription factor 4 (SALL4) expression. As key transcriptional factors in
      maintaining pluripotency, up-regulation of SALL4 and NANOG enhanced
      reprogramming. Moreover, the ability of MSX2 to up-regulate Cdh1, Gata3, Nanog,
      and Sall4 was further potentiated in the presence of Kruppel-like factor 4
      (KLF4). However, MSX2 did not mediate the effects of BMP4 signaling on activation
      of the microRNAs miR-205 and miR-200 or the inhibitory effects that arrested
      reprogramming in the pre-iPSC state. In conclusion, MSX2 partially mediates the
      effects of BMP4 signaling during reprogramming, improving our understanding of
      the role of BMP signaling in MET and of the connection between cell lineage
      specifiers such as MSX2 and GATA3 and pluripotency.

PMID- 30097517
TI  - Receptor recognition by the peroxisomal AAA complex depends on the presence of
      the ubiquitin moiety and is mediated by Pex1p.
AB  - The receptor cycle of type I peroxisomal matrix protein import is completed by
      ubiquitination of the membrane-bound peroxisome biogenesis factor 5 (Pex5p) and
      its subsequent export back to the cytosol. The receptor export is the only ATP
      dependent step of the whole process and is facilitated by two members of the AAA
      family of proteins (ATPases associated with various cellular activities), namely
      Pex1p and Pex6p. To gain further insight into substrate recognition by the AAA
      complex, we generated an N-terminally linked ubiquitin-Pex5p fusion protein. This
      fusion protein displayed biological activity because it is able to functionally
      complement a PEX5-deletion in Saccharomyces cerevisiae. In vitro assays revealed
      its interaction at WT level with the native cargo protein Pcs60p and Pex14p, a
      constituent of the receptor docking complex. We also demonstrate in vitro
      deubiquitination by the deubiquitinating enzyme Ubp15p. In vitro pulldown assays
      and cross-linking studies demonstrate that Pex5p recognition by the AAA complex
      depends on the presence of the ubiquitin moiety and is mediated by Pex1p.

PMID- 30097518
TI  - Sialidase down-regulation reduces non-HDL cholesterol, inhibits leukocyte
      transmigration, and attenuates atherosclerosis in ApoE knockout mice.
AB  - Atherosclerosis is a complex disease that involves alterations in lipoprotein
      metabolism and inflammation. Protein and lipid glycosylation events, such as
      sialylation, contribute to the development of atherosclerosis and are regulated
      by specific glycosidases, including sialidases. To evaluate the effect of the
      sialidase neuraminidase 1 (NEU1) on atherogenesis, here we generated
      apolipoprotein E (ApoE)-deficient mice that express hypomorphic levels of NEU1
      (Neu1hypoApoe-/-). We found that the hypomorphic NEU1 expression in male Apoe-/-
      mice reduces serum levels of very-low-density lipoprotein (VLDL) and LDL
      cholesterol, diminishes infiltration of inflammatory cells into lesions, and
      decreases aortic sinus atherosclerosis. Transplantation of Apoe-/- bone marrow
      (BM) into Neu1hypoApoe-/- mice significantly increased atherosclerotic lesion
      development and had no effect on serum lipoprotein levels. Moreover, Neu1hypoApoe
      /- mice exhibited a reduction in circulating monocyte and neutrophil levels and
      had reduced hyaluronic acid and P-selectin adhesion capability on
      monocytes/neutrophils and T cells. Consistent with these findings, administration
      of a sialidase inhibitor, 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, had a
      significant anti-atherogenic effect in the Apoe-/- mice. In summary, the
      reduction in NEU1 expression or function decreases atherosclerosis in mice via
      its significant effects on lipid metabolism and inflammatory processes. We
      conclude that NEU1 may represent a promising target for managing atherosclerosis.

PMID- 30097519
TI  - Short chain ceramides disrupt immunoreceptor signaling by inhibiting segregation
      of Lo from Ld Plasma membrane components.
AB  - Lipid phase heterogeneity in plasma membranes is thought to play a key role in
      targeting cellular signaling, but efforts to test lipid raft and related
      hypotheses are limited by the spatially dynamic nature of these phase-based
      structures in cells and by experimental characterization tools. We suggest that
      perturbation of plasma membrane structure by lipid derivatives offers a general
      method for assessing functional roles for ordered lipid regions in membrane and
      cell biology. We previously reported that short chain ceramides with either C2 or
      C6 acyl chains inhibit antigen-stimulated Ca2+ mobilization (Gidwani et al.,
      2003). We now show that these short chain ceramides inhibit liquid order (Lo)
      liquid disorder (Ld) phase separation in giant plasma membrane vesicles that
      normally occurs at low temperatures. Furthermore, they are effective inhibitors
      of tyrosine phosphorylation stimulated by antigen, as well as store-operated Ca2+
      entry. In Jurkat T cells, C6-ceramide is also effective at inhibiting Ca2+
      mobilization stimulated by either anti-TCR or thapsigargin, consistent with the
      view that these short chain ceramides effectively interfere with functional
      responses that depend on ordered lipid regions in the plasma membrane.

PMID- 30097521
TI  - Caput medusa in a newborn infant.

PMID- 30097520
TI  - Divergent Hemogen genes of teleosts and mammals share conserved roles in
      erythropoiesis: analysis using transgenic and mutant zebrafish.
AB  - Hemogen is a vertebrate transcription factor that performs important functions in
      erythropoiesis and testicular development and may contribute to neoplasia. Here
      we identify zebrafish Hemogen and show that it is considerably smaller (~22 kDa)
      than its human ortholog (~55 kDa), a striking difference that is explained by an
      underlying modular structure. We demonstrate that Hemogens are largely composed
      of 21-25 amino acid repeats, some of which may function as transactivation
      domains (TADs). Hemogen expression in embryonic and adult zebrafish is detected
      in hematopoietic, renal, neural and gonadal tissues. Using Tol2- and CRISPR/Cas9
      generated transgenic zebrafish, we show that Hemogen expression is controlled by
      two Gata1-dependent regulatory sequences that act alone and together to control
      spatial and temporal expression during development. Partial depletion of Hemogen
      in embryos by morpholino knockdown reduces the number of erythrocytes in
      circulation. CRISPR/Cas9-generated zebrafish lines containing either a frameshift
      mutation or an in-frame deletion in a putative, C-terminal TAD display anemia and
      embryonic tail defects. This work expands our understanding of Hemogen and
      provides mutant zebrafish lines for future study of the mechanism of this
      important transcription factor.

PMID- 30097522
TI  - Perforated necrotising enterocolitis presenting as a rapidly expanding abdominal
      mass in a preterm neonate.

PMID- 30097523
TI  - Wide Range of Clinical Outcomes in Patients with Gliomatosis Cerebri Growth
      Pattern: A Clinical, Radiographic, and Histopathologic Study.
AB  - BACKGROUND: The 2016 World Health Organization Classification of Central Nervous
      System Tumors categorizes gliomatosis cerebri growth pattern (GC) as a subgroup
      of diffuse infiltrating gliomas, defined by extent of brain involvement on
      magnetic resonance imaging (MRI). Clinical and radiographic features in GC
      patients are highly heterogeneous; however, prognosis has historically been
      considered poor. SUBJECTS, MATERIALS, AND METHODS: We performed a retrospective
      search for patients at our institution meeting radiographic criteria of primary,
      type I GC (defined as diffuse tumor infiltration without associated tumor mass
      and contrast enhancement on MRI) and analyzed their clinical, imaging, and
      histopathologic features. RESULTS: A total of 34 patients met radiographic
      criteria of primary, type I GC, and 33 had a confirmed histologic diagnosis of an
      infiltrating glial neoplasm. Age >47 years at diagnosis was associated with worse
      overall survival (OS) compared with age <=47 years (hazard ratio [HR] 1.04, 95%
      confidence interval [CI] 1.01-1.07, p = .003). Patients with grade 2 tumors
      demonstrated a trend for improved OS compared with those with grade 3 tumors (HR
      2.65, 95% CI 0.99-7.08, p = .051). Except for brainstem involvement, extent or
      location of radiographic involvement did not detectably affect clinical outcome.
      IDH mutation status identified a subgroup of GC patients with particularly long
      survival up to 25 years and was associated with longer time to progression (HR
      4.81, 95% CI 0.99-23.47, p = .052). CONCLUSION: Patients with primary, type I GC
      do not uniformly carry a poor prognosis, even in the presence of widespread
      radiographic involvement. Consistent with other reports, IDH mutation status may
      identify patients with improved clinical outcome. Molecular characterization,
      rather than MRI features, may be most valuable for prognostication and management
      of GC patients. IMPLICATIONS FOR PRACTICE: Patients with gliomatosis cerebri
      growth pattern (GC) constitute a challenge to clinicians, given their wide range
      of clinical, histologic, and radiographic presentation, heterogeneous outcome
      patterns, and the lack of consensus on a standardized treatment approach. This
      study highlights that radiographic extent of disease-albeit category-defining
      does not detectably influence survival and that IDH mutations may impact clinical
      outcome. Practicing oncologists should be aware that select GC patients may
      demonstrate exceptionally favorable survival times and prognosticate patients
      based on molecular markers, rather than imaging features alone.

PMID- 30097524
TI  - Effectiveness of First-Line Bevacizumab in Metastatic Colorectal Cancer: The
      Observational Cohort Study GRETA.
AB  - BACKGROUND: Scant real-world data exist on the clinical outcomes associated with
      the use of bevacizumab-containing chemotherapy (B+CT) in patients with metastatic
      colorectal cancer (mCRC). The primary objective of the GRETA cohort study was to
      compare the overall survival (OS) of patients with mCRC treated with first-line
      B+CT versus chemotherapy (CT) alone, in an Italian clinical practice setting.
      MATERIALS AND METHODS: Incident patients with mCRC were identified during the
      period 2010-2012 from five population-based cancer registries in Italy. Cases
      were linked to regional health care utilization databases to obtain the entire
      spectrum of health services provided to each patient. Patients starting a first
      line treatment with B+CT or CT alone within 90 days from the diagnosis were
      included in the study cohort. A propensity score (PS) method was applied to
      account for residual confounding. RESULTS: Of 480 patients with mCRC included in
      the study cohort, 21.0 received first-line B+CT, and 79.0% received CT. Patients
      receiving B+CT were younger (p < .001) and underwent surgery more frequently (p =
      .001). The median OS was 22.5 and 14.6 months for B+CT and CT, respectively (p =
      .011). The corresponding hazard ratios adjusted by multivariate modeling and PS
      matched analysis were 0.82 (95% confidence interval [CI], 0.62-1.08) and 0.86
      (95% CI, 0.56-1.33), respectively. Similar results were observed after
      subgrouping by age and surgery. CONCLUSION: In this Italian real-world setting of
      unselected mCRC, the OS of patients treated with B+CT was consistent with
      previous observational and patient-registry studies. However, definitive evidence
      of an improvement in OS cannot be drawn. IMPLICATIONS FOR PRACTICE: Bevacizumab
      is a well-established first-line treatment for metastatic colorectal cancer.
      However, there is scarce evidence in the literature about its effectiveness in
      clinical practice. Evaluating this topic should be of interest for both
      clinicians and regulatory agencies. In this study, the median overall survival of
      the bevacizumab cohort was strikingly coherent with that reported in large
      observational series of unselected patients, thus suggesting a consistent and
      reproducible effect of the drug in clinical practice. Although consistent results
      were observed both in the overall population and in age and surgery subgroups,
      the present study did not offer definitive evidence of an improvement in OS.

PMID- 30097525
TI  - Preventable Adverse Drug Events Among Inpatients: A Systematic Review.
AB  - : : media-1vid110.1542/5799876436001PEDS-VA_2018-0805Video Abstract CONTEXT:
      Patient harm resulting from medication errors drives prevention efforts, yet harm
      associated with medication errors in children has not been systematically
      reviewed. OBJECTIVE: To review the incidence and severity of preventable adverse
      drug events (pADEs) resulting from medication errors in pediatric inpatient
      settings. DATA SOURCES: Data sources included Cumulative Index of Nursing and
      Allied Health Literature, Medline, Scopus, the Cochrane Library, and Embase.
      STUDY SELECTION: Selected studies were published between January 2000 and
      December 2017, written in the English language, and measured pADEs among
      pediatric hospital inpatients by chart review or direct observation. DATA
      EXTRACTION: Data extracted were medication error and harm definitions, pADE
      incidence and severity rates, items required for quality assessment, and sample
      details. RESULTS: Twenty-two studies were included. For children in general
      pediatric wards, incidence was at 0 to 17 pADEs per 1000 patient days or 1.3% of
      medication errors (of any type) compared with 0 to 29 pADEs per 1000 patient days
      or 1.5% of medication errors in ICUs. Hospital-wide studies contained reports of
      up to 74 pADEs per 1000 patient days or 2.6% of medication errors. The severity
      of pADEs was mainly minor. LIMITATIONS: Limited literature on the severity of
      pADEs is available. Additional study will better illuminate differences among
      hospital wards and among those with or without health information technology.
      CONCLUSIONS: Medication errors in pediatric settings seldom result in patient
      harm, and if they do, harm is predominantly of minor severity. Implementing
      health information technologies was associated with reduced incidence of harm.

PMID- 30097526
TI  - The Persistent Challenge of Understanding Preventable Adverse Drug Events.

PMID- 30097527
TI  - Controversy About a High-Risk and Innovative Fetal Cardiac Intervention.
AB  - A 20-week-old fetus was diagnosed with critical pulmonary valve stenosis. Given
      the ultrasound findings, the outcome was difficult to predict. The fetal
      cardiologists discussed the possibility of a pulmonary valvuloplasty (an
      experimental procedure) with the parents, wherein the fetal right ventricle would
      be punctured with a long 18G needle, and through it, a wire advanced across the
      pulmonary valve, allowing for balloon dilation of the valve. The experimental
      procedure had been performed at a handful of centers. There were some reports of
      success. The parents sought an opinion at one of the referral centers that had
      tried the procedure. The doctors there recommended against it. The doctors at the
      original center were unsure whether they should try the procedure. The parents
      wanted it. In this ethics rounds, doctors and the parents discuss the arguments
      for and against a high-risk, innovative in utero procedure.

PMID- 30097528
TI  - Behavioral Health and Adult Milestones in Young Adults With Perinatal HIV
      Infection or Exposure.
AB  - BACKGROUND: Young adults living with perinatally acquired HIV infection (PHIVYAs)
      are at risk for poor biomedical and behavioral health outcomes. Few studies offer
      a comprehensive overview of the functioning of this population in young adulthood
      and the role of HIV. METHODS: Data come from the Child and Adolescent Self
      Awareness and Health Study, a longitudinal behavioral health cohort study of
      PHIVYAs and perinatally HIV-exposed but uninfected young adults (PHEUYAs) who are
      compared on psychiatric and neurocognitive functioning, sexual and substance use
      behaviors, health and reproductive outcomes, and young adult milestones. RESULTS:
      Overall, 27% of participants met criteria for a psychiatric disorder, including
      mood (11%), anxiety (22%), and substance use (28%), with no HIV status
      differences. PHIVYAs performed worse on 2 neurocognitive tests. There were no HIV
      status differences in condomless sex (41%) or pregnancies (41% women; 38% men).
      Both groups exhibited similar adult milestones: 67% graduated high school or an
      equivalent, 19% were in college, and 42% were employed. However, 38% were neither
      in school or working, 12% reported incarceration, and 16% were ever homeless.
      Among PHIVYAs, 36% were viremic (>200 copies per mL), and 15% were severely
      immunocompromised (CD4+ cell count <100 cells per mm3). CONCLUSIONS: Many PHIVYAs
      achieve adult milestones related to school, employment, sexual relationships, and
      starting families. However, they and PHEUYAs have high rates of psychiatric and
      substance use disorders and behavioral risks, which can jeopardize long-term
      health and adult functioning, particularly in the context of HIV. These findings
      underscore an urgent need to escalate interventions.

PMID- 30097529
TI  - Conventional Dendritic Cells Impair Recovery after Myocardial Infarction.
AB  - Ischemic myocardial injury results in sterile cardiac inflammation that leads to
      tissue repair, two processes controlled by mononuclear phagocytes. Despite global
      burden of cardiovascular diseases, we do not understand the functional
      contribution to pathogenesis of specific cardiac mononuclear phagocyte lineages,
      in particular dendritic cells. To address this limitation, we used detailed
      lineage tracing and genetic studies to identify bona fide murine and human CD103+
      conventional dendritic cell (cDC)1s, CD11b+ cDC2s, and plasmacytoid DCs (pDCs) in
      the heart of normal mice and immunocompromised NSG mice reconstituted with human
      CD34+ cells, respectively. After myocardial infarction (MI), the specific
      depletion of cDCs, but not pDCs, improved cardiac function and prevented adverse
      cardiac remodeling. Our results showed that fractional shortening measured after
      MI was not influenced by the absence of pDCs. Interestingly, however, depletion
      of cDCs significantly improved reduction in fractional shortening. Moreover,
      fibrosis and cell areas were reduced in infarcted zones. This correlated with
      reduced numbers of cardiac macrophages, neutrophils, and T cells, indicating a
      blunted inflammatory response. Accordingly, mRNA levels of proinflammatory
      cytokines IL-1beta and IFN-gamma were reduced. Collectively, our results
      demonstrate the unequivocal pathological role of cDCs following MI.

PMID- 30097530
TI  - Nucleotide Composition of Human Ig Nontemplated Regions Depends on Trimming of
      the Flanking Gene Segments, and Terminal Deoxynucleotidyl Transferase Favors
      Adding Cytosine, Not Guanosine, in Most VDJ Rearrangements.
AB  - The formation of nontemplated (N) regions during Ig gene rearrangement is a major
      contributor to Ab diversity. To gain insights into the mechanisms behind this, we
      studied the nucleotide composition of N regions within 29,962 unique human VHDJH
      rearrangements and 8728 unique human DJH rearrangements containing exactly one
      identifiable D gene segment and thus two N regions, N1 and N2. We found a
      distinct decreasing content of cytosine (C) and increasing content of guanine (G)
      across each N region, suggesting that N regions are typically generated by
      concatenation of two 3' overhangs synthesized by addition of nucleoside
      triphosphates with a preference for dCTP. This challenges the general assumption
      that the terminal deoxynucleotidyl transferase favors dGTP in vivo. Furthermore,
      we found that the G and C gradients depended strongly on whether the germline
      gene segments were trimmed or not. Our data show that C-enriched N addition
      preferentially happens at trimmed 3' ends of VH, D, and JH gene segments,
      indicating a dependency of the transferase mechanism upon the nuclease mechanism.

PMID- 30097531
TI  - Autocrine IL-10 Signaling Promotes Dendritic Cell Type-2 Activation and
      Persistence of Murine Cryptococcal Lung Infection.
AB  - The substantial morbidity and mortality caused by invasive fungal pathogens,
      including Cryptococcus neoformans, necessitates increased understanding of
      protective immune responses against these infections. Our previous work using
      murine models of cryptococcal lung infection demonstrated that dendritic cells
      (DCs) orchestrate critical transitions from innate to adaptive immunity and that
      IL-10 signaling blockade improves fungal clearance. To further understand
      interrelationships among IL-10 production, fungal clearance, and the effect of IL
      10 on lung DCs, we performed a comparative temporal analysis of cryptococcal lung
      infection in wild type C57BL/6J mice (designated IL-10+/+) and IL-10-/- mice
      inoculated intratracheally with C. neoformans (strain 52D). Early and sustained
      IL-10 production by lung leukocytes was associated with persistent infection in
      IL-10+/+ mice, whereas fungal clearance was improved in IL-10-/- mice during the
      late adaptive phase of infection. Numbers of monocyte-derived DCs, T cells, and
      alveolar and exudate macrophages were increased in lungs of IL-10-/- versus IL
      10+/+ mice concurrent with evidence of enhanced DC type-1, Th1/Th17 CD4 cell, and
      classical macrophage activation. Bone marrow-derived DCs stimulated with
      cryptococcal mannoproteins, a component of the fungal capsule, upregulated
      expression of IL-10 and IL-10R, which promoted DC type-2 activation in an
      autocrine manner. Thus, our findings implicate fungus-triggered autocrine IL-10
      signaling and DC type-2 activation as important contributors to the development
      of nonprotective immune effector responses, which characterize persistent
      cryptococcal lung infection. Collectively, this study informs and strengthens the
      rationale for IL-10 signaling blockade as a novel treatment for fungal
      infections.

PMID- 30097532
TI  - Glycomics@ExPASy: Bridging the Gap.
AB  - Glycomics@ExPASy (https://www.expasy.org/glycomics) is the glycomics tab of
      ExPASy, the server of SIB Swiss Institute of Bioinformatics. It was created in
      2016 to centralize web-based glycoinformatics resources developed within an
      international network of glycoscientists. The hosted collection currently
      includes mainly databases and tools created and maintained at SIB but also links
      to a range of reference resources popular in the glycomics community. The
      philosophy of our toolbox is that it should be {glycoscientist AND protein
      scientist}-friendly with the aim of (1) popularizing the use of bioinformatics in
      glycobiology and (2) emphasizing the relationship between glycobiology and
      protein-oriented bioinformatics resources. The scarcity of data bridging these
      two disciplines led us to design tools as interactive as possible based on
      database connectivity to facilitate data exploration and support hypothesis
      building. Glycomics@ExPASy was designed, and is developed, with a long-term
      vision in close collaboration with glycoscientists to meet as closely as possible
      the growing needs of the community for glycoinformatics.

PMID- 30097533
TI  - Discovery of a Human Testis-specific Protein Complex TEX101-DPEP3 and Selection
      of Its Disrupting Antibodies.
AB  - TEX101 is a testis-specific protein expressed exclusively in male germ cells and
      is a validated biomarker of male infertility. Studies in mice suggest that TEX101
      is a cell-surface chaperone which regulates, through protein-protein
      interactions, the maturation of proteins involved in spermatozoa transit and
      oocyte binding. Male TEX101-null mice are sterile. Here, we identified by co
      immunoprecipitation-mass spectrometry the interactome of human TEX101 in
      testicular tissues and spermatozoa. The testis-specific cell-surface dipeptidase
      3 (DPEP3) emerged as the top hit. We further validated the TEX101-DPEP3 complex
      by using hybrid immunoassays. Combinations of antibodies recognizing different
      epitopes of TEX101 and DPEP3 facilitated development of a simple immunoassay to
      screen for disruptors of TEX101-DPEP3 complex. As a proof-of-a-concept, we
      demonstrated that anti-TEX101 antibody T4 disrupted the native TEX101-DPEP3
      complex. Disrupting antibodies may be used to study the human TEX101-DPEP3
      complex, and to develop modulators for male fertility.

PMID- 30097534
TI  - Evaluation of Serum Glycoprotein Biomarker Candidates for Detection of Esophageal
      Adenocarcinoma and Surveillance of Barrett's Esophagus.
AB  - Esophageal adenocarcinoma (EAC) is thought to develop from asymptomatic Barrett's
      esophagus (BE) with a low annual rate of conversion. Current endoscopy
      surveillance of BE patients is probably not cost-effective. Previously, we
      discovered serum glycoprotein biomarker candidates which could discriminate BE
      patients from EAC. Here, we aimed to validate candidate serum glycoprotein
      biomarkers in independent cohorts, and to develop a biomarker candidate panel for
      BE surveillance. Serum glycoprotein biomarker candidates were measured in 301
      serum samples collected from Australia (4 states) and the United States (1
      clinic) using previously established lectin magnetic bead array (LeMBA) coupled
      multiple reaction monitoring mass spectrometry (MRM-MS) tier 3 assay. The area
      under receiver operating characteristic curve (AUROC) was calculated as a measure
      of discrimination, and multivariate recursive partitioning was used to formulate
      a multi-marker panel for BE surveillance. Complement C9 (C9), gelsolin (GSN),
      serum paraoxonase/arylesterase 1 (PON1) and serum paraoxonase/lactonase 3 (PON3)
      were validated as diagnostic glycoprotein biomarkers in lectin pull-down samples
      for EAC across both cohorts. A panel of 10 serum glycoprotein biomarker
      candidates discriminated BE patients not requiring intervention (BE+/- low grade
      dysplasia) from those requiring intervention (BE with high grade dysplasia (BE
      HGD) or EAC) with an AUROC value of 0.93. Tissue expression of C9 was found to be
      induced in BE, dysplastic BE and EAC. In longitudinal samples from subjects that
      have progressed toward EAC, levels of serum C9 were significantly (p < 0.05)
      increased with disease progression in EPHA (erythroagglutinin from Phaseolus
      vulgaris) and NPL (Narcissus pseudonarcissus lectin) pull-down samples. The
      results confirm alteration of complement pathway glycoproteins during BE-EAC
      pathogenesis. Further prospective clinical validation of the confirmed biomarker
      candidates in a large cohort is warranted, prior to development of a first-line
      BE surveillance blood test.

PMID- 30097536
TI  - The continuum of screening and early detection, awareness and faster diagnosis of
      lung cancer.

PMID- 30097535
TI  - Comprehensive Proteomics Identification of IFN-lambda3-regulated Antiviral
      Proteins in HBV-transfected Cells.
AB  - Interferon lambda (IFN-lambda) is a relatively unexplored, yet promising
      antiviral agent. IFN-lambda has recently been tested in clinical trials of
      chronic hepatitis B virus infection (CHB), with the advantage that side effects
      may be limited compared with IFN-alpha, as IFN-lambda receptors are found only in
      epithelial cells. To date, IFN-lambda's downstream signaling pathway remains
      largely unelucidated, particularly via proteomics methods. Here, we report that
      IFN-lambda3 inhibits HBV replication in HepG2.2.15 cells, reducing levels of both
      HBV transcripts and intracellular HBV DNA. Quantitative proteomic analysis of HBV
      transfected cells was performed following 24-hour IFN-lambda3 treatment, with
      parallel IFN-alpha2a and PBS treatments for comparison using a dimethyl labeling
      method. The depth of the study allowed us to map the induction of antiviral
      proteins to multiple points of the viral life cycle, as well as facilitating the
      identification of antiviral proteins not previously known to be elicited upon HBV
      infection (e.g. IFITM3, XRN2, and NT5C3A). This study also shows up-regulation of
      many effectors involved in antigen processing/presentation indicating that this
      cytokine exerted immunomodulatory effects through several essential molecules for
      these processes. Interestingly, the 2 subunits of the immunoproteasome cap (PSME1
      and PSME2) were up-regulated whereas cap components of the constitutive
      proteasome were down-regulated upon both IFN treatments, suggesting coordinated
      modulation toward the antigen processing/presentation mode. Furthermore, in
      addition to confirming canonical activation of interferon-stimulated gene (ISG)
      transcription through the JAK-STAT pathway, we reveal that IFN-lambda3 restored
      levels of RIG-I and RIG-G, proteins known to be suppressed by HBV. Enrichment
      analysis demonstrated that several biological processes including RNA metabolism,
      translation, and ER-targeting were differentially regulated upon treatment with
      IFN-lambda3 versus IFN-alpha2a. Our proteomic data suggests that IFN-lambda3
      regulates an array of cellular processes to control HBV replication.

PMID- 30097537
TI  - Fibroblastic reticular cells initiate immune responses in visceral adipose
      tissues and secure peritoneal immunity.
AB  - Immune protection of the body cavities depends on the swift activation of innate
      and adaptive immune responses in nonclassical secondary lymphoid organs known as
      fat-associated lymphoid clusters (FALCs). Compared with classical secondary
      lymphoid organs such as lymph nodes and Peyer's patches, FALCs develop along
      distinct differentiation trajectories and display a reduced structural
      complexity. Although it is well established that fibroblastic reticular cells
      (FRCs) are an integral component of the immune-stimulating infrastructure of
      classical secondary lymphoid organs, the role of FRCs in FALC-dependent
      peritoneal immunity remains unclear. Using FRC-specific gene targeting, we found
      that FRCs play an essential role in FALC-driven immune responses. Specifically,
      we report that initiation of peritoneal immunity was governed through FRC
      activation in a myeloid differentiation primary response 88 (MYD88)-dependent
      manner. FRC-specific ablation of MYD88 blocked recruitment of inflammatory
      monocytes into FALCs and subsequent CD4+ T cell-dependent B-cell activation and
      IgG class switching. Moreover, containment of Salmonella infection was
      compromised in mice lacking MYD88 expression in FRCs, indicating that FRCs in
      FALCs function as an initial checkpoint in the orchestration of protective immune
      responses in the peritoneal cavity.

PMID- 30097538
TI  - Coalescence and Linkage Disequilibrium in Facultatively Sexual Diploids.
AB  - Under neutrality, linkage disequilibrium results from physically linked sites
      having nonindependent coalescent histories. In obligately sexual organisms,
      meiotic recombination is the dominant force separating linked variants from one
      another, and thus in determining the decay of linkage disequilibrium with
      physical distance. In facultatively sexual diploid organisms that principally
      reproduce clonally, mechanisms of mitotic exchange are expected to become
      relatively more important in shaping linkage disequilibrium. Here we outline
      mathematical and computational models of a facultative-sex coalescent process
      that includes meiotic and mitotic recombination, via both crossovers and gene
      conversion, to determine how linkage disequilibrium is affected with facultative
      sex. We demonstrate that the degree to which linkage disequilibrium is broken
      down by meiotic recombination simply scales with the probability of sex if it is
      sufficiently high (much greater than [Formula: see text] for population size N).
      However, with very rare sex (occurring with frequency on the order of [Formula:
      see text]), mitotic gene conversion plays a particularly important and
      complicated role because it both breaks down associations between sites and
      removes within-individual diversity. Strong population structure under rare sex
      leads to lower average linkage disequilibrium values than in panmictic
      populations, due to the influence of low-frequency polymorphisms created by
      allelic sequence divergence acting in individual subpopulations. These analyses
      provide information on how to interpret observed linkage disequilibrium patterns
      in facultative sexuals and to determine what genomic forces are likely to shape
      them.

PMID- 30097540
TI  - Reply to Pandey et al.: Understanding the efficacy of a potential antiretroviral
      drug candidate in humanized mouse model of HIV infection.

PMID- 30097541
TI  - Do the pharmacokinetic and pharmacodynamic graphs warrant additional explanation?

PMID- 30097539
TI  - Glucocorticoid receptor recruits to enhancers and drives activation by motif
      directed binding.
AB  - Glucocorticoids are potent steroid hormones that regulate immunity and metabolism
      by activating the transcription factor (TF) activity of glucocorticoid receptor
      (GR). Previous models have proposed that DNA binding motifs and sites of
      chromatin accessibility predetermine GR binding and activity. However, there are
      vast excesses of both features relative to the number of GR binding sites. Thus,
      these features alone are unlikely to account for the specificity of GR binding
      and activity. To identify genomic and epigenetic contributions to GR binding
      specificity and the downstream changes resultant from GR binding, we performed
      hundreds of genome-wide measurements of TF binding, epigenetic state, and gene
      expression across a 12-h time course of glucocorticoid exposure. We found that
      glucocorticoid treatment induces GR to bind to nearly all pre-established
      enhancers within minutes. However, GR binds to only a small fraction of the set
      of accessible sites that lack enhancer marks. Once GR is bound to enhancers, a
      combination of enhancer motif composition and interactions between enhancers then
      determines the strength and persistence of GR binding, which consequently
      correlates with dramatic shifts in enhancer activation. Over the course of
      several hours, highly coordinated changes in TF binding and histone modification
      occupancy occur specifically within enhancers, and these changes correlate with
      changes in the expression of nearby genes. Following GR binding, changes in the
      binding of other TFs precede changes in chromatin accessibility, suggesting that
      other TFs are also sensitive to genomic features beyond that of accessibility.

PMID- 30097542
TI  - Accelerated RNA secondary structure design using preselected sequences for
      helices and loops.
AB  - Nucleic acids can be designed to be nano-machines, pharmaceuticals, or probes.
      RNA secondary structures can form the basis of self-assembling nanostructures.
      There are only four natural RNA bases, therefore it can be difficult to design
      sequences that fold to a single, specified structure because many other
      structures are often possible for a given sequence. One approach taken by state
      of-the-art sequence design methods is to select sequences that fold to the
      specified structure using stochastic, iterative refinement. The goal of this work
      is to accelerate design. Many existing iterative methods select and refine
      sequences one base pair and one unpaired nucleotide at a time. Here, the
      hypothesis that sequences can be preselected in order to accelerate design was
      tested. To this aim, a database was built of helix sequences that demonstrate
      thermodynamic features found in natural sequences and that also have little
      tendency to cross-hybridize. Additionally, a database was assembled of RNA loop
      sequences with low helix-formation propensity and little tendency to cross
      hybridize with either the helices or other loops. These databases of preselected
      sequences accelerate the selection of sequences that fold with minimal ensemble
      defect by replacing some of the trial and error of current refinement approaches.
      When using the database of preselected sequences as compared to randomly chosen
      sequences, sequences for natural structures are designed 36 times faster, and
      random structures are designed six times faster. The sequences selected with the
      aid of the database have similar ensemble defect as those sequences selected at
      random. The sequence database is part of RNAstructure package at
      http://rna.urmc.rochester.edu/RNAstructure.html.

PMID- 30097544
TI  - Cross-leg free flap for limb salvage in the setting of radiation.
AB  - Limb salvage in an irradiated patient with limited recipient vessels leaves few
      options for reconstruction. Cross-leg free flaps have been used to reconstruct
      defects that would otherwise lead to amputation in patients with no ipsilateral
      recipient vessels. We present the first documented case of a cross-leg free flap
      for limb salvage in a radiated bed after infection and tumour resection.

PMID- 30097543
TI  - Signal transduction-dependent small regulatory RNA is involved in glutamate
      metabolism of the human pathogen Bordetella pertussis.
AB  - Bordetella pertussis is the causative agent of human whooping cough, a highly
      contagious respiratory disease which despite vaccination programs remains the
      major cause of infant morbidity and mortality. The requirement of the RNA
      chaperone Hfq for virulence of B. pertussis suggested that Hfq-dependent small
      regulatory RNAs are involved in the modulation of gene expression. High
      throughput RNA sequencing revealed hundreds of putative noncoding RNAs including
      the RgtA sRNA. Abundance of RgtA is strongly decreased in the absence of the Hfq
      protein and its expression is modulated by the activities of the two-component
      regulatory system BvgAS and another response regulator RisA. Whereas RgtA levels
      were elevated under modulatory conditions or in the absence of bvg genes,
      deletion of the risA gene completely abolished RgtA expression. Profiling of the
      DeltargtA mutant in the DeltabvgA genetic background identified the BP3831 gene
      encoding a periplasmic amino acid-binding protein of an ABC transporter as a
      possible target gene. The results of site-directed mutagenesis and in silico
      analysis indicate that RgtA base-pairs with the region upstream of the start
      codon of the BP3831 mRNA and thereby weakens the BP3831 protein production.
      Furthermore, our data suggest that the function of the BP3831 protein is related
      to transport of glutamate, an important metabolite in the B. pertussis
      physiology. We propose that the BvgAS/RisA interplay regulates the expression of
      RgtA which upon infection, when glutamate might be scarce, attenuates translation
      of the glutamate transporter and thereby assists in adaptation of the pathogen to
      other sources of energy.

PMID- 30097545
TI  - Kikuchi-Fujimoto disease: a rare cause of cervical lymphadenopathy and fever.
AB  - A 28-year-old Pakistani man with previously treated latent tuberculosis (TB)
      presented with a 3-month history of productive cough, fever, drenching night
      sweats, anorexia, sore throat and tender left cervical lymphadenopathy. Extensive
      biochemical and microbiological tests, and imaging studies were all inconclusive.
      Lymph node biopsy revealed the diagnosis of Kikuchi-Fujimoto disease (KFD). He
      had persistent fever and anorexia during admission despite supportive measures
      which resolved quickly on starting prednisolone. He remained well after being
      weaned off steroids on 18 weeks' follow-up. KFD is a rare, self-limiting disease
      which can mimic several serious conditions such as TB and lymphoma. Prompt
      diagnosis with lymph node biopsy is paramount in addressing diagnostic
      uncertainty and avoids starting potentially toxic treatment on these patients.

PMID- 30097546
TI  - Johanson-Blizzard syndrome with associated urogenital anomalies.
AB  - We present a case of a child with pancreatic insufficiency and facial defects
      typical of Johanson-Blizzard syndrome (JBS), along with the more facultative
      anomalies of the JBS, such as those of the urogenital system including persistent
      urogenital sinus, urethral duplication and dysplastic kidneys. Fetal ultrasound
      in a 21-year-old G1P1 woman revealed ambiguous genitalia. Examination at birth
      revealed a phallic structure with urethral meatus, non-palpable gonads, two
      orifices in close proximity in the perineum, with the anterior being a common
      urogenital channel and the posterior, the rectum. A voiding
      cystourethrogram/genitogram showed bilateral high-grade vesicoureteral reflux and
      a common urogenital sinus extending 1.5 cm before dividing into three channels:
      the native urethra, an accessory urethra directed anteriorly towards the clitoris
      and a septate vagina with uterus didelphys. JBS was suspected by clinical
      presentation and confirmed by UBR1 molecular testing (46,XX). At 16 months of
      age, she underwent feminising genitoplasty and posterior sagittal anorectoplasty.

PMID- 30097547
TI  - Bitter experience with liquorice sweetening agent resulting in apparent
      mineralocorticoid excess with periodic paralysis.
AB  - Chronic liquorice ingestion is a rare cause of secondary hypertension and
      hypokalaemia with periodic paralysis. We report the case of a middle-aged Indian
      man who presented with hypertension and hypokalaemic alkalosis with recurrent
      bouts of periodic paralysis. Biochemical investigations revealed suppressed
      plasma renin and aldosterone concentrations with normal cortisol concentration. A
      detailed history revealed that he was addicted for the last 5 years to a form of
      chewing tobacco mixed with herbal preparations as a sweetening agent which on
      analysis revealed active principles of glycyrrhizin using the thin liquid
      chromatography method. The hypokalaemia resolved and hypertension control
      improved significantly after discontinuing liquorice consumption, and the patient
      was asymptomatic at 1-year follow-up. Long-term liquorice ingestion should be
      kept in mind as a reversible cause of hypokalaemic periodic paralysis, with a
      meticulous history and biochemical evaluation helping in identifying this
      recognisable and curable medical disorder.

PMID- 30097548
TI  - Unexpected cause for eyelid swelling and ptosis: rigid gas permeable contact lens
      migration following a 28-year-old trauma.
AB  - A patient presented with left upper eyelid swelling and ptosis. The MRI reported
      a cyst with proteinaceous content. On surgical excision of the cyst, a rigid gas
      permeable (RGP) contact lens was found. The RGP lens was encapsulated within the
      upper eyelid soft tissue. It was later revealed that the patient experienced
      childhood trauma while wearing RGP contact lenses 28 years previously. The
      patient assumed that the RGP lens fell out and was lost; however, it can be
      inferred that the lens migrated into the eyelid and resided there
      asymptomatically for 28 years.

PMID- 30097549
TI  - Post-traumatic bony impingement into vagina: a rare cause of urethrovaginal
      fistula.
AB  - A 22-year-old woman met with road traffic accident 6 months back following which
      she underwent exploratory laparotomy with intraperitoneal bladder rupture repair.
      She presented with urethrovaginal fistula due to a fragment of fractured pubic
      bone impinging into the anterior vaginal wall. The findings were confirmed on CT
      scan and cystoscopy. The patient was managed with removal of the bony spicule and
      transvaginal repair of urethrovaginal fistula with Martius fat pad interposition.

PMID- 30097550
TI  - Shadow over abdomen.

PMID- 30097551
TI  - Mediastinal lipoblastoma: a rare entity discovered on physical exam.

PMID- 30097552
TI  - Tools for your stroke team: adapting crew-resource management for acute stroke
      care.
AB  - Crew-resource management is an approach to work and training that focuses on non
      technical skills and strategies to prevent human error in complex procedures. It
      was initially termed 'cockpit-resource management' and developed for aviation in
      the 1970s after several severe accidents; it has contributed to a measurable
      increase in flight safety. In recent years, this approach has been successfully
      implemented in other high-reliability environments; surgical disciplines have
      made particular use of crew-resource management strategies and training, with
      resulting reduced mortality rates. The stepwise implementation of different crew
      resource management strategies in stroke care at our tertiary stroke centre has
      helped to speed up process times significantly, and to improve patient safety and
      staff satisfaction. Here, we summarise our experience in adapting different crew
      resource management tools to acute stroke care, sharing specific tools that have
      proven valuable in our hands, and we encourage colleagues to implement such
      strategies in acute stroke care.

PMID- 30097553
TI  - Rheumatoid leptomeningitis presenting with an acute neuropsychiatric disorder.
AB  - Leptomeningitis is a rare central nervous system manifestation of rheumatoid
      arthritis, generally in patients with established chronic rheumatoid disease. We
      report a 41-year-old man without previous rheumatoid arthritis or psychiatric
      disorder who presented with an acute neuropsychiatric disturbance and
      polyarthralgia. His MR scan of brain showed asymmetric bifrontal leptomeningitis,
      confirmed on (18F)-fluoro-D-glucose-positron emission tomography. Other
      investigations showed highly positive serum and cerebrospinal fluid anti-cyclic
      citrullinated peptide. A leptomeningeal biopsy showed necrotising leptomeningeal
      inflammation with ill-defined granulomas and lymphoplasmacytic infiltrate without
      organisms. Prolonged high-dose corticosteroids and then rituximab resulted in
      recovery. Chronic leptomeningitis can present with an acute neuropsychiatric
      disorder. We highlight that early rheumatoid disease can, rarely, cause a chronic
      leptomeningitis, reversible with immunotherapy.

PMID- 30097554
TI  - How do trainee doctors introduce themselves to patients?
AB  - OBJECTIVES: To identify how trainee doctors introduce themselves to patients.
      DESIGN: Survey. SETTING: Chelsea and Westminster Hospital, London. PARTICIPANTS:
      One hundred trainee doctors, of mixed grades and specialties. MAIN OUTCOME
      MEASURES: Introducing oneself by name, using their professional title 'Dr', use
      of the term 'trainee'. RESULTS: All 100 participants introduced themselves by
      name to patients, with 63% using only their first name, 18% using only their last
      name and 18% using a combination of both. 67% mentioned their specialty and 18%
      mentioned their training grade. 85% identified themselves as a doctor, but only
      22% used their professional title (Dr), and only 6% introduced themselves by
      name, grade, specialty and title. 80% varied the way they introduced themselves
      to patients, depending on several factors including the clinical situation and
      patients' characteristics/features. 56% said that they had changed the way they
      introduced themselves over time, and 42% deliberately avoided the term 'trainee'
      during introductions. There was no association between trainees' age, gender or
      specialty and their comfort in describing themselves as 'trainees', but the more
      junior trainees were more comfortable using this term than the senior grades
      (p<0.0001). Overall, 76% disliked the term 'trainee', for various reasons.
      CONCLUSION: All doctors in this study introduced themselves by name but the
      majority did not specify their training grade or trainee status, predominantly
      because they believed it could trigger anxiety around their competence or
      undermine confidence in their abilities.

PMID- 30097556
TI  - All three IP3 receptor subtypes generate Ca2+ puffs, the universal building
      blocks of IP3-evoked Ca2+ signals.
AB  - All three subtypes of inositol 1,4,5-trisphosphate receptor (IP3R) are
      intracellular Ca2+ channels that are co-regulated by IP3 and Ca2+ This allows
      IP3Rs to evoke regenerative Ca2+ signals, the smallest of which are Ca2+ puffs
      that reflect the coordinated opening of a few clustered IP3Rs. We use total
      internal reflection microscopy (TIRF) microscopy to record Ca2+ signals in HEK
      cells expressing all three IP3R subtypes or a single native subtype. Ca2+ puffs
      are less frequent in cells expressing one IP3R subtype, commensurate with them
      expressing fewer IP3Rs than wild-type cells. However, all three IP3R subtypes
      generate broadly similar Ca2+ puffs with similar numbers of IP3Rs contributing to
      each. This suggests that IP3R clusters may be assembled by conserved mechanisms
      that generate similarly sized clusters across different IP3R expression levels.
      The Ca2+ puffs evoked by IP3R2 had slower kinetics and more prolonged durations,
      which may be due to IP3 binding with greater affinity to IP3R2. We conclude that
      Ca2+ puffs are the building blocks for the Ca2+ signals evoked by all IP3Rs.

PMID- 30097555
TI  - SCML2 promotes heterochromatin organization in late spermatogenesis.
AB  - Spermatogenesis involves the progressive reorganization of heterochromatin.
      However, the mechanisms that underlie the dynamic remodeling of heterochromatin
      remain unknown. Here, we identify SCML2, a germline-specific Polycomb protein, as
      a critical regulator of heterochromatin organization in spermatogenesis. We show
      that SCML2 accumulates on pericentromeric heterochromatin (PCH) in male germ
      cells, where it suppresses PRC1-mediated monoubiquitylation of histone H2A at
      Lysine 119 (H2AK119ub) and promotes deposition of PRC2-mediated H3K27me3 during
      meiosis. In postmeiotic spermatids, SCML2 is required for heterochromatin
      organization, and the loss of SCML2 leads to the formation of ectopic patches of
      facultative heterochromatin. Our data suggest that, in the absence of SCML2, the
      ectopic expression of somatic lamins drives this process. Furthermore, the
      centromere protein CENP-V is a specific marker of PCH in postmeiotic spermatids,
      and SCML2 is required for CENP-V localization on PCH. Given the essential
      functions of PRC1 and PRC2 for genome-wide gene expression in spermatogenesis,
      our data suggest that heterochromatin organization and spermatogenesis-specific
      gene expression are functionally linked. We propose that SCML2 coordinates the
      organization of heterochromatin and gene expression through the regulation of
      Polycomb complexes.

PMID- 30097557
TI  - Ivy1 is a negative regulator of Gtr-dependent TORC1 activation.
AB  - The highly conserved TORC1 complex controls cell growth in response to nutrients,
      especially amino acids. The EGO complex activates TORC1 in response to glutamine
      and leucine. Here, we demonstrate that the I-BAR domain-containing protein Ivy1
      colocalizes with Gtr1 and Gtr2, a heterodimer of small GTPases that are part of
      the EGO complex. Ivy1 is a negative regulator of Gtr-induced TORC1 activation,
      and is contained within puncta associated with the vacuolar membrane in cells
      grown in nutrient-rich medium or after brief nitrogen starvation. Addition of
      glutamine to nitrogen-starved cells leads to dissipation of Ivy1 puncta and
      redistribution of Ivy1 throughout the vacuolar membrane. Continued stimulation
      with glutamine results in concentration of Ivy1 within vacuolar membrane
      invaginations and its spatial separation from the EGO complex components Gtr1 and
      Gtr2. Disruption of vacuolar membrane invagination is associated with persistent
      mislocalization of Ivy1 across the vacuolar membrane and inhibition of TORC1
      activity. Together, our findings illustrate a novel negative-feedback pathway
      that is exerted by Ivy1 on Gtr-dependent TORC1 signaling and provide insight into
      a potential molecular mechanism underlying TORC1 activation by vacuolar membrane
      remodeling.

PMID- 30097559
TI  - Clinical Use of a New Nano-Hydroxyapatite/Polyamide66 Composite Artificial Lamina
      in Spinal Decompression Surgery: More Than 4 Years' Follow-Up.
AB  - BACKGROUND Long-term follow-up results showed that epidural scar formation and
      adhesion after laminectomy always affected the outcomes of repeat operations. The
      establishment of a barrier between scar tissue and dura was effective in
      preventing epidural scar formation. MATERIAL AND METHODS A nano
      hydroxyapatite/polyamide66 (n-HA/PA66) artificial lamina was designed and
      fabricated and used to cover the opened spinal canal in patients who received
      laminectomy. The visual analogue scale (VAS) and Japanese Orthopedic Association
      (JOA) Scores, X-ray, computed tomography, and magnetic resonance imaging results
      were periodically recorded and evaluated. RESULTS All patients were followed up
      for 4-7 years, with an average period of 5.2 years. The clinical symptoms
      improved significantly after surgery, as the JOA scores were significantly
      improved after the operation and maintained to last follow-up when compared with
      preoperative ones (P<0.05). The vertebral canal became noticeably enlarged, from
      16.7+/-4.7 mm to 32.9+/-2.2 mm, after surgery and well maintained to 32.1+/-1.8
      mm. The lumbar lordosis was well maintained after surgery. No rupture,
      absorption, or dislodgement of the n-HA/PA66 lamina was found. MRI showed the
      spinal canal had the correct morphology, with no stenosis, no obvious scar
      formation, and no nerve roots or epidural sac compression. CONCLUSIONS The
      artificial lamina is a reasonable choice for prevention of epidural scar
      formation after laminectomy, in spite of the results from a small sample of
      cases.

PMID- 30097560
TI  - Difficult Wiring of a Recanalized Thrombotic Lesion in the Right Coronary Artery
      Analyzed with Optical Coherence Tomography.
AB  - BACKGROUND Recanalized thrombi are usually unrecognized in conventional coronary
      angiography. However, multiple channels have been observed in recanalized
      thrombotic lesions. Therefore, the wire apparently crosses the lesion in some
      difficult cases. We analyzed the cause of difficult wiring of a recanalized
      thrombotic lesion using optical coherence tomography (OCT). CASE REPORT An 87
      year-old man with chest pain was admitted to our hospital. Coronary angiography
      showed significant stenosis of the proximal right coronary artery with irregular
      linear filling and haziness. Crossing of the wire for the lesion was very
      difficult but was achieved using a parallel wire technique. OCT clearly
      demonstrated multiple small channels which had ambiguous findings on angiography
      and intravascular ultrasound. These structures showed a honeycomb-like appearance
      suggests the recanalized thrombi. A drug-eluting stent was subsequently deployed
      to fully cover the entire lesion. CONCLUSIONS OCT is useful to evaluate the
      accurate tissue characteristics of a recanalized thrombotic lesion. Because
      recanalized thrombi have multiple small channels and since there are some cases
      in which a part of the channel only flows into a side branch, it is necessary to
      carefully monitor wiring at the time of percutaneous coronary intervention.

PMID- 30097558
TI  - The unusual flagellar-targeting mechanism and functions of the trypanosome
      ortholog of the ciliary GTPase Arl13b.
AB  - The small GTPase Arl13b is one of the most conserved and ancient ciliary
      proteins. In human and animals, Arl13b is primarily associated with the ciliary
      membrane, where it acts as a guanine-nucleotide-exchange factor (GEF) for Arl3
      and is implicated in a variety of ciliary and cellular functions. We have
      identified and characterized Trypanosoma brucei (Tb)Arl13, the sole Arl13b
      homolog in this evolutionarily divergent, protozoan parasite. TbArl13 has
      conserved flagellar functions and exhibits catalytic activity towards two
      different TbArl3 homologs. However, TbArl13 is distinctly associated with the
      axoneme through a dimerization/docking (D/D) domain. Replacing the D/D domain
      with a sequence encoding a flagellar membrane protein created a viable
      alternative to the wild-type TbArl13 in our RNA interference (RNAi)-based rescue
      assay. Therefore, flagellar enrichment is crucial for TbArl13, but mechanisms to
      achieve this could be flexible. Our findings thus extend the understanding of the
      roles of Arl13b and Arl13b-Arl3 pathway in a divergent flagellate of medical
      importance.This article has an associated First Person interview with the first
      author of the paper.

PMID- 30097561
TI  - RBFOX2 and alternative splicing in B-cell lymphoma.

PMID- 30097562
TI  - Iron-based trinuclear metal-organic nanostructures on a surface with local charge
      accumulation.
AB  - Coordination chemistry relies on harnessing active metal sites within organic
      matrices. Polynuclear complexes-where organic ligands bind to several metal atoms
      are relevant due to their electronic/magnetic properties and potential for
      functional reactivity pathways. However, their synthesis remains challenging; few
      geometries and configurations have been achieved. Here, we synthesise-via
      supramolecular chemistry on a noble metal surface-one-dimensional metal-organic
      nanostructures composed of terpyridine (tpy)-based molecules coordinated with
      well-defined polynuclear iron clusters. Combining low-temperature scanning probe
      microscopy and density functional theory, we demonstrate that the coordination
      motif consists of coplanar tpy's linked via a quasi-linear tri-iron node in a
      mixed (positive-)valence metal-metal bond configuration. This unusual linkage is
      stabilised by local accumulation of electrons between cations, ligand and
      surface. The latter, enabled by bottom-up on-surface synthesis, yields an
      electronic structure that hints at a chemically active polynuclear metal centre,
      paving the way for nanomaterials with novel catalytic/magnetic functionalities.

PMID- 30097563
TI  - N2 activation on a molybdenum-titanium-sulfur cluster.
AB  - The FeMo-cofactor of nitrogenase, a metal-sulfur cluster that contains eight
      transition metals, promotes the conversion of dinitrogen into ammonia when stored
      in the protein. Although various metal-sulfur clusters have been synthesized over
      the past decades, their use in the activation of N2 has remained challenging, and
      even the FeMo-cofactor extracted from nitrogenase is not able to reduce N2.
      Herein, we report the activation of N2 by a metal-sulfur cluster that contains
      molybdenum and titanium. An N2 moiety bridging two [Mo3S4Ti] cubes is converted
      into NH3 and N2H4 upon treatment with Bronsted acids in the presence of a
      reducing agent.

PMID- 30097564
TI  - Understanding the apparent fractional charge of protons in the aqueous
      electrochemical double layer.
AB  - A detailed atomic-scale description of the electrochemical interface is essential
      to the understanding of electrochemical energy transformations. In this work, we
      investigate the charge of solvated protons at the Pt(111) | H2O and Al(111) | H2O
      interfaces. Using semi-local density-functional theory as well as hybrid
      functionals and embedded correlated wavefunction methods as higher-level
      benchmarks, we show that the effective charge of a solvated proton in the
      electrochemical double layer or outer Helmholtz plane at all levels of theory is
      fractional, when the solvated proton and solvent band edges are aligned correctly
      with the Fermi level of the metal (EF). The observed fractional charge in the
      absence of frontier band misalignment arises from a significant overlap between
      the proton and the electron density from the metal surface, and results in an
      energetic difference between protons in bulk solution and those in the outer
      Helmholtz plane.

PMID- 30097566
TI  - The silicon cycle impacted by past ice sheets.
AB  - Globally averaged riverine silicon (Si) concentrations and isotope composition
      (delta30Si) may be affected by the expansion and retreat of large ice sheets
      during glacial-interglacial cycles. Here we provide evidence of this based on the
      delta30Si composition of meltwater runoff from a Greenland Ice Sheet catchment.
      Glacier runoff has the lightest delta30Si measured in running waters (-0.25 +/-
      0.120/00), significantly lower than nonglacial rivers (1.25 +/- 0.680/00), such
      that the overall decline in glacial runoff since the Last Glacial Maximum (LGM)
      may explain 0.06-0.170/00 of the observed ocean delta30Si rise (0.5-1.00/00). A
      marine sediment core proximal to Iceland provides further evidence for transient,
      low-delta30Si meltwater pulses during glacial termination. Diatom Si uptake
      during the LGM was likely similar to present day due to an expanded Si inventory,
      which raises the possibility of a feedback between ice sheet expansion, enhanced
      Si export to the ocean and reduced CO2 concentration in the atmosphere, because
      of the importance of diatoms in the biological carbon pump.

PMID- 30097567
TI  - Maximal viral information recovery from sequence data using VirMAP.
AB  - Accurate classification of the human virome is critical to a full understanding
      of the role viruses play in health and disease. This implies the need for
      sensitive, specific, and practical pipelines that return precise outputs while
      still enabling case-specific post hoc analysis. Viral taxonomic characterization
      from metagenomic data suffers from high background noise and signal crosstalk
      that confounds current methods. Here we develop VirMAP that overcomes these
      limitations using techniques that merge nucleotide and protein information to
      taxonomically classify viral reconstructions independent of genome coverage or
      read overlap. We validate VirMAP using published data sets and viral mock
      communities containing RNA and DNA viruses and bacteriophages. VirMAP offers
      opportunities to enhance metagenomic studies seeking to define virome-host
      interactions, improve biosurveillance capabilities, and strengthen molecular
      epidemiology reporting.

PMID- 30097565
TI  - Commensal microflora-induced T cell responses mediate progressive
      neurodegeneration in glaucoma.
AB  - Glaucoma is the most prevalent neurodegenerative disease and a leading cause of
      blindness worldwide. The mechanisms causing glaucomatous neurodegeneration are
      not fully understood. Here we show, using mice deficient in T and/or B cells and
      adoptive cell transfer, that transient elevation of intraocular pressure (IOP) is
      sufficient to induce T-cell infiltration into the retina. This T-cell
      infiltration leads to a prolonged phase of retinal ganglion cell degeneration
      that persists after IOP returns to a normal level. Heat shock proteins (HSP) are
      identified as target antigens of T-cell responses in glaucomatous mice and human
      glaucoma patients. Furthermore, retina-infiltrating T cells cross-react with
      human and bacterial HSPs; mice raised in the absence of commensal microflora do
      not develop glaucomatous T-cell responses or the associated neurodegeneration.
      These results provide compelling evidence that glaucomatous neurodegeneration is
      mediated in part by T cells that are pre-sensitized by exposure to commensal
      microflora.

PMID- 30097568
TI  - Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in
      children with autism.
AB  - The identification of brain-targeted autoantibodies in children with autism
      spectrum disorder (ASD) raises the possibility of autoimmune encephalopathy
      (AIE). Intravenous immunoglobulin (IVIG) is effective for AIE and for some
      children with ASD. Here, we present the largest case series of children with ASD
      treated with IVIG. Through an ASD clinic, we screened 82 children for AIE, 80 of
      them with ASD. IVIG was recommended for 49 (60%) with 31 (38%) receiving the
      treatment under our care team. The majority of parents (90%) reported some
      improvement with 71% reporting improvements in two or more symptoms. In a subset
      of patients, Aberrant Behavior Checklist (ABC) and/or Social Responsiveness Scale
      (SRS) were completed before and during IVIG treatment. Statistically significant
      improvement occurred in the SRS and ABC. The antidopamine D2L receptor antibody,
      the anti-tubulin antibody and the ratio of the antidopamine D2L to D1 receptor
      antibodies were related to changes in the ABC. The Cunningham Panel predicted
      SRS, ABC, parent-based treatment responses with good accuracy. Adverse effects
      were common (62%) but mostly limited to the infusion period. Only two (6%)
      patients discontinued IVIG because of adverse effects. Overall, our open-label
      case series provides support for the possibility that some children with ASD may
      benefit from IVIG. Given that adverse effects are not uncommon, IVIG treatment
      needs to be considered cautiously. We identified immune biomarkers in select IVIG
      responders but larger cohorts are needed to study immune biomarkers in more
      detail. Our small open-label exploratory trial provides evidence supporting a
      neuroimmune subgroup in patients with ASD.

PMID- 30097570
TI  - Long-term deep-supercooling of large-volume water and red cell suspensions via
      surface sealing with immiscible liquids.
AB  - Supercooling of aqueous solutions is a fundamentally and practically important
      physical phenomenon with numerous applications in biopreservation and beyond.
      Under normal conditions, heterogeneous nucleation mechanisms critically prohibit
      the simultaneous long-term (> 1 week), large volume (> 1 ml), and low
      temperatures (< -10  degrees C) supercooling of aqueous solutions. Here, we
      report on the use of surface sealing of water by an oil phase to significantly
      diminish the primary heterogeneous nucleation at the water/air interface. We
      achieve deep supercooling (down to -20  degrees C) of large volumes of water (up
      to 100 ml) for long periods (up to 100 days) simultaneously via this approach.
      Since oils are mixtures of various hydrocarbons we also report on the use of pure
      alkanes and primary alcohols of various lengths to achieve the same. Furthermore,
      we demonstrate the utility of deep supercooling via preliminary studies on
      extended (100 days) preservation of human red blood cells.

PMID- 30097569
TI  - Notch3-dependent beta-catenin signaling mediates EGFR TKI drug persistence in
      EGFR mutant NSCLC.
AB  - EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung
      cancer, but resistance universally develops. The involvement of beta-catenin in
      EGFR TKI resistance has been previously reported, however, the precise mechanism
      by which beta-catenin activation contributes to EGFR TKI resistance is not clear.
      Here, we show that EGFR inhibition results in the activation of beta-catenin
      signaling in a Notch3-dependent manner, which facilitates the survival of a
      subset of cells that we call "adaptive persisters". We previously reported that
      EGFR-TKI treatment rapidly activates Notch3, and here we describe the physical
      association of Notch3 with beta-catenin, leading to increased stability and
      activation of beta-catenin. We demonstrate that the combination of EGFR-TKI and a
      beta-catenin inhibitor inhibits the development of these adaptive persisters,
      decreases tumor burden, improves recurrence free survival, and overall survival
      in xenograft models. These results supports combined EGFR-TKI and beta-catenin
      inhibition in patients with EGFR mutant lung cancer.

PMID- 30097572
TI  - A balance between aerodynamic and olfactory performance during flight in
      Drosophila.
AB  - The ability to track odor plumes to their source (food, mate, etc.) is key to the
      survival of many insects. During this odor-guided navigation, flapping wings
      could actively draw odorants to the antennae to enhance olfactory sensitivity,
      but it is unclear if improving olfactory function comes at a cost to aerodynamic
      performance. Here, we computationally quantify the odor plume features around a
      fruit fly in forward flight and confirm that the antenna is well positioned to
      receive a significant increase of odor mass flux (peak 1.8 times), induced by
      wing flapping, vertically from below the body but not horizontally. This
      anisotropic odor spatial sampling may have important implications for behavior
      and the algorithm during plume tracking. Further analysis also suggests that,
      because both aerodynamic and olfactory functions are indispensable during odor
      guided navigation, the wing shape and size may be a balance between the two
      functions.

PMID- 30097571
TI  - A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to
      immune checkpoint blockers.
AB  - The biological determinants of sensitivity and resistance to immune checkpoint
      blockers are not completely understood. To elucidate the role of intratumoral T
      cells and their association with the tumor genomic landscape, we perform paired
      whole exome DNA sequencing and multiplexed quantitative immunofluorescence (QIF)
      in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients
      treated with PD-1 axis blockers. QIF is used to simultaneously measure the level
      of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell proliferation (Ki
      67 in CD3) and effector capacity (Granzyme-B in CD3). Elevated mutational load,
      candidate class-I neoantigens or intratumoral CD3 signal are significantly
      associated with favorable response to therapy. Additionally, a "dormant" TIL
      signature is associated with survival benefit in patients treated with immune
      checkpoint blockers characterized by elevated TILs with low activation and
      proliferation. We further demonstrate that dormant TILs can be reinvigorated upon
      PD-1 blockade in a patient-derived xenograft model.

PMID- 30097574
TI  - Optimized HepaRG is a suitable cell source to generate the human liver chimeric
      mouse model for the chronic hepatitis B virus infection.
AB  - The human liver chimeric mouse with primary human hepatocytes (PHHs) engraftment
      has been demonstrated to be a useful animal model to study hepatitis B virus
      (HBV) pathogenesis and evaluate anti-HBV drugs. However, the disadvantages of
      using PHHs include the inability for cellular expansion in vitro, limited donor
      availability, individual differences, and ethical issues, necessitating the
      development of alternatives. To obtain in vitro expandable hepatocytes, we
      optimized the hepatic differentiation procedure of the human liver progenitor
      cell line, HepaRG, using four functional small molecules (4SM) and enriched the
      precursor hepatocyte-like cells (HLCs). HepaRG cells of different hepatic
      differentiation states were engrafted to immunodeficient mice (FRGS) with weekly
      4SM treatment. The HepaRG-engrafted mice were challenged with HBV and/or treated
      with several antivirals to evaluate their effects. We demonstrated that the 4SM
      treatment enhanced hepatic differentiation and promoted cell proliferation
      capacity both in vitro and in vivo. Mice engrafted with enriched HepaRG of
      prehepatic differentiation and treated with 4SM displayed approximately 10% liver
      chimerism at week 8 after engraftment and were maintained at this level for
      another 16 weeks. Therefore, we developed a HepaRG-based human liver chimeric
      mouse model: HepaRG-FRGS. Our experimental results showed that the liver
      chimerism of the mice was adequate to support chronic HBV infection for 24 weeks
      and to evaluate antivirals. We also demonstrated that HBV infection in HepaRG
      cells was dependent on their hepatic differentiation state and liver chimerism in
      vivo. Overall, HepaRG-FRGS mice provide a novel human liver chimeric mouse model
      to study chronic HBV infection and evaluate anti-HBV drugs.

PMID- 30097573
TI  - Programmed cell removal by calreticulin in tissue homeostasis and cancer.
AB  - Macrophage-mediated programmed cell removal (PrCR) is a process essential for the
      clearance of unwanted (damaged, dysfunctional, aged, or harmful) cells. The
      detection and recognition of appropriate target cells by macrophages is a
      critical step for successful PrCR, but its molecular mechanisms have not been
      delineated. Here using the models of tissue turnover, cancer immunosurveillance,
      and hematopoietic stem cells, we show that unwanted cells such as aging
      neutrophils and living cancer cells are susceptible to "labeling" by secreted
      calreticulin (CRT) from macrophages, enabling their clearance through PrCR.
      Importantly, we identified asialoglycans on the target cells to which CRT binds
      to regulate PrCR, and the availability of such CRT-binding sites on cancer cells
      correlated with the prognosis of patients in various malignancies. Our study
      reveals a general mechanism of target cell recognition by macrophages, which is
      the key for the removal of unwanted cells by PrCR in physiological and
      pathophysiological processes.

PMID- 30097575
TI  - The physical, mental, and social impact of COPD in a population-based sample:
      results from the Longitudinal Aging Study Amsterdam.
AB  - Chronic obstructive pulmonary disease (COPD) is associated with substantial
      health impact that may already become apparent in early disease. This study aims
      to examine the features of subjects with COPD in a Dutch population-based sample
      and compare their physical status, mental status, and social status to non-COPD
      subjects. This study made use of Longitudinal Aging Study Amsterdam (LASA) data.
      Demographics, clinical characteristics, self-reported diseases, post
      bronchodilator spirometry, physical, mental, and social status were assessed. A
      number of 810 subjects (50.5% male, mean age 60.5 +/- 2.9 years) were included.
      Subjects with COPD (n = 68, mean FEV1 67.6 [IQR 60.4-80.4] %.) had a slower
      walking speed than non-COPD subjects, p = 0.033. When compared to non-COPD
      subjects, COPD subjects gave a lower rating on their health (physical subscale of
      SF-12: 15 [IQR 16.0-19.0] vs. 18 [IQR 11.0-17.0] points) and life (EQ5D VAS: 75
      [IQR 70.0-90.0] vs. 80 points [IQR 65.0-85.5]) surveys. COPD subjects also had a
      more impaired disease-specific health status (CAT: 9.5 +/- 5.9 vs. 6.7 +/- 5.2,
      respectively), were less likely to have a partner (69% vs. 84%, respectively) and
      received emotional support less often (24% vs. 36%, respectively) compared to non
      COPD subjects (All comparisons p < 0.001). In a population-based sample, subjects
      with COPD had a reduced physical performance, a more impaired disease-specific
      health status and were more socially deprived compared to non-COPD subjects.
      These impairments need to be taken into consideration when setting up a
      management program for patients with mild COPD.

PMID- 30097576
TI  - Elongator mutation in mice induces neurodegeneration and ataxia-like behavior.
AB  - Cerebellar ataxias are severe neurodegenerative disorders with an early onset and
      progressive and inexorable course of the disease. Here, we report a single point
      mutation in the gene encoding Elongator complex subunit 6 causing Purkinje neuron
      degeneration and an ataxia-like phenotype in the mutant wobbly mouse. This
      mutation destabilizes the complex and compromises its function in translation
      regulation, leading to protein misfolding, proteotoxic stress, and eventual
      neuronal death. In addition, we show that substantial microgliosis is triggered
      by the NLRP3 inflammasome pathway in the cerebellum and that blocking NLRP3
      function in vivo significantly delays neuronal degeneration and the onset of
      ataxia in mutant animals. Our data provide a mechanistic insight into the
      pathophysiology of a cerebellar ataxia caused by an Elongator mutation,
      substantiating the increasing body of evidence that alterations of this complex
      are broadly implicated in the onset of a number of diverse neurological
      disorders.

PMID- 30097577
TI  - Multiple timescales of normalized value coding underlie adaptive choice behavior.
AB  - Adaptation is a fundamental process crucial for the efficient coding of sensory
      information. Recent evidence suggests that similar coding principles operate in
      decision-related brain areas, where neural value coding adapts to recent reward
      history. However, the circuit mechanism for value adaptation is unknown, and the
      link between changes in adaptive value coding and choice behavior is unclear.
      Here we show that choice behavior in nonhuman primates varies with the statistics
      of recent rewards. Consistent with efficient coding theory, decision-making shows
      increased choice sensitivity in lower variance reward environments. Both the
      average adaptation effect and across-session variability are explained by a novel
      multiple timescale dynamical model of value representation implementing divisive
      normalization. The model predicts empirical variance-driven changes in behavior
      despite having no explicit knowledge of environmental statistics, suggesting that
      distributional characteristics can be captured by dynamic model architectures.
      These findings highlight the importance of treating decision-making as a dynamic
      process and the role of normalization as a unifying computation for contextual
      phenomena in choice.

PMID- 30097578
TI  - Lensfree OLEDs with over 50% external quantum efficiency via external scattering
      and horizontally oriented emitters.
AB  - High efficiency is important for successful deployment of any light sources.
      Continued efforts have recently made it possible to demonstrate organic light
      emitting diodes with efficiency comparable to that of inorganic light-emitting
      diodes. However, such achievements were possible only with the help of a
      macroscopic lens or complex internal nanostructures, both of which undermine the
      key benefits of organic light-emitting diodes as an affordable planar light
      source. Here we present a systematic way to achieve organic light-emitting diodes
      with ultrahigh efficiency even only with an external scattering film, one of the
      simplest low-cost outcoupling structures. Through a global, multivariable
      analysis, we show that scattering with a high degree of forwardness has a
      potential to play a critical role in realizing ultimate efficiency. Combined with
      horizontally oriented emitters, organic light-emitting diodes equipped with
      particle-embedded films tailored for forward-intensive scattering achieve a
      maximum external quantum efficiency of 56%.

PMID- 30097579
TI  - Brain-computer-interface-based intervention re-normalizes brain functional
      network topology in children with attention deficit/hyperactivity disorder.
AB  - A brain-computer-interface (BCI)-based attention training game system has shown
      promise for treating attention deficit/hyperactivity disorder (ADHD) children
      with inattentive symptoms. However, little is known about brain network
      organizational changes underlying behavior improvement following BCI-based
      training. To cover this gap, we aimed to examine the topological alterations of
      large-scale brain functional networks induced by the 8-week BCI-based attention
      intervention in ADHD boys using resting-state functional magnetic resonance
      imaging method. Compared to the non-intervention (ADHD-NI) group, the
      intervention group (ADHD-I) showed greater reduction of inattention symptoms
      accompanied with differential brain network reorganizations after training.
      Specifically, the ADHD-NI group had increased functional connectivity (FC) within
      the salience/ventral attention network (SVN) and increased FC between task
      positive networks (including the SVN, dorsal attention (DAN), somatomotor, and
      executive control network) and subcortical regions; in contrast ADHD-I group did
      not have this pattern. In parallel, ADHD-I group had reduced degree centrality
      and clustering coefficient as well as increased closeness in task-positive and
      the default mode networks (prefrontal regions) after the training. More
      importantly, these reduced local functional processing mainly in the SVN were
      associated with less inattentive/internalizing problems after 8-week BCI-based
      intervention across ADHD patients. Our findings suggest that the BCI-based
      attention training facilitates behavioral improvement in ADHD children by
      reorganizing brain functional network from more regular to more random
      configurations, particularly renormalizing salience network processing. Future
      long-term longitudinal neuroimaging studies are needed to develop the BCI-based
      intervention approach to promote brain maturation in ADHD.

PMID- 30097580
TI  - Targeting AURKA-CDC25C axis to induce synthetic lethality in ARID1A-deficient
      colorectal cancer cells.
AB  - ARID1A, a component of the SWI/SNF chromatin remodeling complex, is a tumor
      suppressor with a high frequency of inactivating mutations in many cancers.
      Therefore, ARID1A deficiency has been exploited therapeutically for treating
      cancer. Here we show that ARID1A has a synthetic lethal interaction with aurora
      kinase A (AURKA) in colorectal cancer (CRC) cells. Pharmacological and genetic
      perturbations of AURKA selectively inhibit the growth of ARID1A-deficient CRC
      cells. Mechanistically, ARID1A occupies the AURKA gene promoter and negatively
      regulates its transcription. Cells lacking ARID1A show enhanced AURKA
      transcription, which leads to the persistent activation of CDC25C, a key protein
      for G2/M transition and mitotic entry. Inhibiting AURKA activity in ARID1A
      deficient cells significantly increases G2/M arrest and induces cellular
      multinucleation and apoptosis. This study shows a novel synthetic lethality
      interaction between ARID1A and AURKA and indicates that pharmacologically
      inhibiting the AURKA-CDC25C axis represents a novel strategy for treating CRC
      with ARID1A loss-of-function mutations.

PMID- 30097581
TI  - Nuclear-resident RIG-I senses viral replication inducing antiviral immunity.
AB  - The nucleus represents a cellular compartment where the discrimination of self
      from non-self nucleic acids is vital. While emerging evidence establishes a
      nuclear non-self DNA sensing paradigm, the nuclear sensing of non-self RNA, such
      as that from nuclear-replicating RNA viruses, remains unexplored. Here, we report
      the identification of nuclear-resident RIG-I actively involved in nuclear viral
      RNA sensing. The nuclear RIG-I, along with its cytoplasmic counterpart, senses
      influenza A virus (IAV) nuclear replication leading to a cooperative induction of
      type I interferon response. Its activation signals through the canonical
      signaling axis and establishes an effective antiviral state restricting IAV
      replication. The exclusive signaling specificity conferred by nuclear RIG-I is
      reinforced by its inability to sense cytoplasmic-replicating Sendai virus and
      appreciable sensing of hepatitis B virus pregenomic RNA in the nucleus. These
      results refine the RNA sensing paradigm for nuclear-replicating viruses and
      reveal a previously unrecognized subcellular milieu for RIG-I-like receptor
      sensing.

PMID- 30097583
TI  - Growth tradeoffs produce complex microbial communities on a single limiting
      resource.
AB  - The relationship between the dynamics of a community and its constituent pairwise
      interactions is a fundamental problem in ecology. Higher-order ecological effects
      beyond pairwise interactions may be key to complex ecosystems, but mechanisms to
      produce these effects remain poorly understood. Here we model microbial growth
      and competition to show that higher-order effects can arise from variation in
      multiple microbial growth traits, such as lag times and growth rates, on a single
      limiting resource with no other interactions. These effects produce a range of
      ecological phenomena: an unlimited number of strains can exhibit multistability
      and neutral coexistence, potentially with a single keystone strain; strains that
      coexist in pairs do not coexist all together; and a strain that wins all pairwise
      competitions can go extinct in a mixed competition. Since variation in multiple
      growth traits is ubiquitous in microbial populations, our results indicate these
      higher-order effects may also be widespread, especially in laboratory ecology and
      evolution experiments.

PMID- 30097584
TI  - Beneficial effects of climate warming on boreal tree growth may be transitory.
AB  - Predicted increases in temperature and aridity across the boreal forest region
      have the potential to alter timber supply and carbon sequestration. Given the
      widely-observed variation in species sensitivity to climate, there is an urgent
      need to develop species-specific predictive models that can account for local
      conditions. Here, we matched the growth of 270,000 trees across a 761,100 km2
      region with detailed site-level data to quantify the growth responses of the
      seven most common boreal tree species in Eastern Canada to changes in climate.
      Accounting for spatially-explicit species-specific responses, we find that while
      2  degrees C of warming may increase overall forest productivity by 13 +/- 3%
      (mean +/- SE) in the absence of disturbance, additional warming could reverse
      this trend and lead to substantial declines exacerbated by reductions in water
      availability. Our results confirm the transitory nature of warming-induced growth
      benefits in the boreal forest and highlight the vulnerability of the ecosystem to
      excess warming and drying.

PMID- 30097582
TI  - Biology and genome of a newly discovered sibling species of Caenorhabditis
      elegans.
AB  - A 'sibling' species of the model organism Caenorhabditis elegans has long been
      sought for use in comparative analyses that would enable deep evolutionary
      interpretations of biological phenomena. Here, we describe the first sibling
      species of C. elegans, C. inopinata n. sp., isolated from fig syconia in Okinawa,
      Japan. We investigate the morphology, developmental processes and behaviour of C.
      inopinata, which differ significantly from those of C. elegans. The 123-Mb C.
      inopinata genome was sequenced and assembled into six nuclear chromosomes,
      allowing delineation of Caenorhabditis genome evolution and revealing unique
      characteristics, such as highly expanded transposable elements that might have
      contributed to the genome evolution of C. inopinata. In addition, C. inopinata
      exhibits massive gene losses in chemoreceptor gene families, which could be
      correlated with its limited habitat area. We have developed genetic and molecular
      techniques for C. inopinata; thus C. inopinata provides an exciting new platform
      for comparative evolutionary studies.

PMID- 30097585
TI  - Capacitive neural network with neuro-transistors.
AB  - Experimental demonstration of resistive neural networks has been the recent focus
      of hardware implementation of neuromorphic computing. Capacitive neural networks,
      which call for novel building blocks, provide an alternative physical embodiment
      of neural networks featuring a lower static power and a better emulation of
      neural functionalities. Here, we develop neuro-transistors by integrating dynamic
      pseudo-memcapacitors as the gates of transistors to produce electronic analogs of
      the soma and axon of a neuron, with "leaky integrate-and-fire" dynamics augmented
      by a signal gain on the output. Paired with non-volatile pseudo-memcapacitive
      synapses, a Hebbian-like learning mechanism is implemented in a capacitive
      switching network, leading to the observed associative learning. A prototypical
      fully integrated capacitive neural network is built and used to classify inputs
      of signals.

PMID- 30097586
TI  - AEBP1 promotes epithelial-mesenchymal transition of gastric cancer cells by
      activating the NF-kappaB pathway and predicts poor outcome of the patients.
AB  - Adipocyte enhancer binding protein 1 (AEBP1) is a transcriptional repressor that
      plays a critical role in regulating adipogenesis. Recent studies have indicated
      that AEBP1 might function as a candidate oncogene and is overexpressed in several
      human malignancies. However, the role of AEBP1 in gastric cancer (GC) remains
      largely unknown. This study aimed to investigate the expression pattern,
      prognostic significance and biological function of AEBP1 in human gastric cancer
      and to explore the underlying mechanism. We found that both the mRNA and protein
      levels of AEBP1 were significantly increased in human GC tissues. Elevated AEBP1
      expression was significantly correlated with poor overall survival in patients
      with both early-stage (Tumor, Node, Metastases (TNM) TNM I and II) and late-stage
      (TNM III and IV) GC. Silencing AEBP1 markedly suppressed the proliferation,
      migration, invasion, metastasis and epithelial-mesenchymal transition of GC
      cells. Moreover, we demonstrated that knockdown of AEBP1 in GC cells led to
      inhibition of the NF-kappaB pathway by hampering the degradation of IkappaBalpha.
      Thus, AEBP1 might be served as a promising prognostic indicator and a potential
      therapeutic target in human GC.

PMID- 30097587
TI  - Isocorroles as Homoaromatic NIR-Absorbing Chromophores: A First Quantum Chemical
      Study.
AB  - Density functional theory calculations of magnetically induced current densities
      have revealed high diatropic ring currents in unsubstituted isocorrole consistent
      with homoaromatic character. An examination of the Kohn-Sham molecular orbitals
      showed clear evidence of homoconjugative interactions in four occupied pi-type
      molecular orbitals as well as in the LUMO. Remarkably, substituents at the
      saturated meso position were found to exert a dramatic influence on the overall
      current density pattern. Thus, whereas bis(trimethylsilyl)-substitution strongly
      enhanced the peripheral diatropic current (consistent with enhanced
      homoaromaticity), difluoro-substitution engendered a strong, net paratropic
      current (consistent with antihomoaromaticity). In this respect, isocorroles stand
      in sharp contrast to benzenoid aromatics, for which substituents typically exert
      a small influence on the current density distribution.

PMID- 30097588
TI  - Genome-wide association study and genomic prediction using parental and breeding
      populations of Japanese pear (Pyrus pyrifolia Nakai).
AB  - Breeding of fruit trees is hindered by their large size and long juvenile period.
      Genome-wide association study (GWAS) and genomic selection (GS) are promising
      methods for circumventing this hindrance, but preparing new large datasets for
      these methods may not always be practical. Here, we evaluated the potential of
      breeding populations evaluated routinely in breeding programs for GWAS and GS. We
      used a pear parental population of 86 varieties and breeding populations of 765
      trees from 16 full-sib families, which were phenotyped for 18 traits and
      genotyped for 1,506 single nucleotide polymorphisms (SNPs). The power of GWAS and
      accuracy of genomic prediction were improved when we combined data from the
      breeding populations and the parental population. The accuracy of genomic
      prediction was improved further when full-sib data of the target family were
      available. The results suggest that phenotype data collected in breeding programs
      can be beneficial for GWAS and GS when they are combined with genome-wide marker
      data. The potential of GWAS and GS will be further extended if we can build a
      system for routine collection of the phenotype and marker genotype data for
      breeding populations.

PMID- 30097589
TI  - Monitoring bone changes due to calcium, magnesium, and phosphorus loss in rat
      femurs using Quantitative Ultrasound.
AB  - Bone mineral density is an important parameter for the diagnosis of bone
      diseases, as well as for predicting fractures and treatment monitoring. Thus, the
      aim of the present study was to evaluate the potential of Quantitative Ultrasound
      (QUS) to monitor bone changes after calcium, phosphorus, and magnesium loss in
      rat femurs in vitro during a demineralization process. Four quantitative
      ultrasound parameters were estimated from bone surface echoes in eight femur
      diaphysis of rats. The echo signals were acquired during a decalcification
      process by Ethylenediaminetetraacetic Acid (EDTA). The results were compared to
      Quantitative Computed Tomography (QCT) and inductively coupled plasma optical
      emission spectrometry measurements for validation. Integrated Reflection
      Coefficient (IRC) reflection parameters and Frequency Slope of Reflection
      Transfer Function (FSRTF) during demineralization tended to decrease, while the
      backscattering parameter Apparent Integrated Backscatter (AIB) increased and
      Frequency Slope of Apparent Backscatter (FSAB) showed an oscillatory behavior
      with no defined trend. Results indicate a clear relation between demineralization
      and the corresponding decrease in the reflection parameters and increase in the
      scattering parameters. The trend analysis of the fall curve of the chemical
      elements showed a better relationship between IRC and QCT. It was possible to
      monitor bone changes after ions losses, through the QUS. Thus, it is an
      indication that the proposed protocol has potential to characterize bone tissue
      in animal models, providing consistent results towards standardization of bone
      characterization studies by QUS endorsing its use in humans.

PMID- 30097590
TI  - Cholesterol modulates acetylcholine receptor diffusion by tuning confinement
      sojourns and nanocluster stability.
AB  - Translational motion of neurotransmitter receptors is key for determining
      receptor number at the synapse and hence, synaptic efficacy. We combine live-cell
      STORM superresolution microscopy of nicotinic acetylcholine receptor (nAChR) with
      single-particle tracking, mean-squared displacement (MSD), turning angle,
      ergodicity, and clustering analyses to characterize the lateral motion of
      individual molecules and their collective behaviour. nAChR diffusion is highly
      heterogeneous: subdiffusive, Brownian and, less frequently, superdiffusive. At
      the single-track level, free walks are transiently interrupted by ms-long
      confinement sojourns occurring in nanodomains of ~36 nm radius. Cholesterol
      modulates the time and the area spent in confinement. Turning angle analysis
      reveals anticorrelated steps with time-lag dependence, in good agreement with the
      permeable fence model. At the ensemble level, nanocluster assembly occurs in
      second-long bursts separated by periods of cluster disassembly. Thus, millisecond
      long confinement sojourns and second-long reversible nanoclustering with similar
      cholesterol sensitivities affect all trajectories; the proportion of the two
      regimes determines the resulting macroscopic motional mode and breadth of
      heterogeneity in the ensemble population.

PMID- 30097591
TI  - Computer-Guided Surface Engineering for Enzyme Improvement.
AB  - Protein engineering strategies are often guided by our understanding of how the
      structure of a protein determines its function. However, our understanding is
      generally restricted to small regions of a protein, namely the active site and
      its immediate vicinity, while the remainder of the protein is something of an
      enigma. Studying highly homologous transaminases with strictly conserved active
      sites, but different substrate preferences and activities, we predict and
      experimentally validate that the surface of the protein far from the active site
      carries out a decisive role in substrate selectivity and catalytic efficiency.
      Using a unique molecular dynamics approach and novel trajectory analysis, we
      demonstrate the phenomenon of surface-directed ligand diffusion in this well
      known protein family for the first time. Further, we identify the residues
      involved in directing substrate, design surface channel variants endowed for
      improved kinetic properties and establish a broadly applicable new approach for
      protein engineering.

PMID- 30097592
TI  - Design considerations for the enhancement of human color vision by breaking
      binocular redundancy.
AB  - To see color, the human visual system combines the response of three types of
      cone cells in the retina-a compressive process that discards a significant amount
      of spectral information. Here, we present designs based on thin-film optical
      filters with the goal of enhancing human color vision by breaking its inherent
      binocular redundancy, providing different spectral content to each eye. We
      fabricated a set of optical filters that "splits" the response of the short
      wavelength cone between the two eyes in individuals with typical trichromatic
      vision, simulating the presence of approximately four distinct cone types. Such
      an increase in the number of effective cone types can reduce the prevalence of
      metamers-pairs of distinct spectra that resolve to the same tristimulus values.
      This technique may result in an enhancement of spectral perception, with
      applications ranging from camouflage detection and anti-counterfeiting to new
      types of artwork and data visualization.

PMID- 30097593
TI  - Exosomes released from pancreatic cancer cells enhance angiogenic activities via
      dynamin-dependent endocytosis in endothelial cells in vitro.
AB  - Pancreatic cancer has the lowest 5 year survival rate among all cancers. Several
      extracellular factors are involved in the development and metastasis of
      pancreatic cancer to distant organs. Exosomes are lipid-bilayer, membrane
      enclosed nanoparticles that are recognised as important mediators of cell-to-cell
      communications. However, the role of exosomes released from pancreatic cancer
      cells in tumour micro-environment remains unknown. Here, we show that exosomes
      released from pancreatic cancer PK-45H cells activate various gene expressions in
      human umbilical vein endothelial cells (HUVECs) by in vitro analyses. In
      addition, these exosomes released from PK-45H cells promote phosphorylation of
      Akt and ERK1/2 signalling pathway molecules and tube formation via dynamin
      dependent endocytosis in HUVECs. Our findings suggested that exosomes released
      from pancreatic cancer cells may act as a novel angiogenesis promoter.

PMID- 30097594
TI  - Gemcitabine treatment promotes immunosuppressive microenvironment in pancreatic
      tumors by supporting the infiltration, growth, and polarization of macrophages.
AB  - Chemotherapy-induced immunosuppression poses an additional challenge to its
      limited efficacy in pancreatic cancer (PC). Here we investigated the effect of
      gemcitabine on macrophages, which are the first line of immune-defense
      mechanisms. We observed an increased presence of macrophages in orthotopic human
      pancreatic tumor xenografts from mice treated with gemcitabine as compared to
      those from vehicle only-treated mice. Conditioned media from gemcitabine-treated
      PC cells (Gem-CM) promoted growth, migration and invasion of RAW264.7 macrophage.
      In addition, Gem-CM also induced upregulation of M2-polarized macrophage markers,
      arginase-1 and TGF-beta1. Cytokine profiling of gemcitabine-treated PC cells
      identified IL-8 as the most differentially-expressed cytokine. Incubation of Gem
      CM with IL-8 neutralizing antibody diminished its ability to induce growth,
      migration and invasion of RAW264.7 macrophages, but did not abrogate their M2
      polarization. Together, our findings identify IL-8 as an important mediator in
      the gemcitabine-induced infiltration of macrophages within the pancreatic tumor
      microenvironment and suggest the requirement of additional mechanism(s) for
      macrophage polarization.

PMID- 30097596
TI  - Author Correction: Allogenic and Autogenic Signals in the Stratigraphic Record of
      the Deep-Sea Bengal Fan.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30097595
TI  - Circadian clock disruption by selective removal of endogenous carbon monoxide.
AB  - Circadian rhythms are regulated by transcription-translation feedback loops
      (TTFL) of clock genes. Previous studies have demonstrated that core
      transcriptional factors, NPAS2 and CLOCK, in the TTFL can reversibly bind carbon
      monoxide (CO) in vitro. However, little is known about whether endogenous CO,
      which is continuously produced during a heme metabolic process, is involved in
      the circadian system. Here we show that selective removal of endogenous CO in
      mice considerably disrupts rhythmic expression of the clock genes. A highly
      selective CO scavenger, hemoCD1, which is a supramolecular complex of an
      iron(II)porphyrin with a per-O-methyl-beta-cyclodextrin dimer, was used to remove
      endogenous CO in mice. Intraperitoneal administration of hemoCD1 to mice
      immediately reduced the amount of internal CO. The removal of CO promoted the
      bindings of NPAS2 and CLOCK to DNA (E-box) in the murine liver, resulting in up
      regulation of the E-box-controlled clock genes (Per1, Per2, Cry1, Cry2, and Rev
      erbalpha). Within 3 h after the administration, most hemoCD1 in mice was excreted
      in the urine, and heme oxygenase-1 (HO-1) was gradually induced in the liver.
      Increased endogenous CO production due to the overexpression of HO-1 caused
      dissociation of NPAS2 and CLOCK from E-box, which in turn induced down-regulation
      of the clock genes. The down-regulation continued over 12 h even after the
      internal CO level recovered to normal. The late down-regulation was ascribed to
      an inflammatory response caused by the endogenous CO reduction. The CO pseudo
      knockdown experiments provided the clear evidence that endogenous CO contributes
      to regulation in the mammalian circadian clock.

PMID- 30097597
TI  - Resting-state alpha power is selectively associated with autistic traits
      reflecting behavioral rigidity.
AB  - Previous research suggests that variation in at-rest neural activity correlates
      with specific domains of the ASD phenotype; however, few studies have linked
      patterns of brain activity with autistic trait expression in typically developing
      populations. The purpose of this study was to examine associations between
      resting-state electroencephalography (EEG) and three domains of the broader
      autism phenotype (social interest, rigidity, and pragmatic language) in typically
      developing individuals. High-density scalp EEG was recorded in thirty-seven
      typically developing adult participants (13 male, aged 18-52 years). The Broad
      Autism Phenotype Questionnaire (BAP-Q) was used to measure autistic trait
      expression. Absolute alpha power (8-13 Hz) was extracted from eyes-closed epochs
      using spectral decomposition techniques. Analyses revealed a specific positive
      association between scores on the BAP-Q Rigidity subscale and alpha power in the
      parietal scalp region. No significant associations were found between alpha power
      and the BAP-Q Aloofness or Pragmatic Language subscales. Furthermore, the
      association between EEG power and behavioral rigidity was specific to the alpha
      frequency band. This study demonstrates that specific traits within the broader
      autism phenotype are associated with dissociable patterns of at-rest neural
      activity.

PMID- 30097598
TI  - A superfolder variant of pH-sensitive pHluorin for in vivo pH measurements in the
      endoplasmic reticulum.
AB  - Many cellular processes are regulated via pH, and maintaining the pH of different
      organelles is crucial for cell survival. A pH-sensitive GFP variant, the so
      called pHluorin, has proven to be a valuable tool to study the pH of the cytosol,
      mitochondria and other organelles in vivo. We found that the fluorescence
      intensity of Endoplasmic Reticulum (ER)-targeted pHluorin in the yeast
      Saccharomyces cerevisiae was very low and barely showed pH sensitivity, probably
      due to misfolding in the oxidative environment of the ER. We therefore developed
      a superfolder variant of pHluorin which enabled us to monitor pH changes in the
      ER and the cytosol of S. cerevisiae in vivo. The superfolder pHluorin variant is
      likely to be functional in cells of different organisms as well as in additional
      compartments that originate from the secretory pathway like the Golgi apparatus
      and pre-vacuolar compartments, and therefore has a broad range of possible future
      applications.

PMID- 30097600
TI  - Biological significance and prognostic relevance of peripheral blood neutrophil
      to-lymphocyte ratio in soft tissue sarcoma.
AB  - Peripheral blood indices of systemic inflammation such as the neutrophil
      lymphocyte ratio (NLR) have been shown to be prognostic in various cancers. We
      aim to investigate the clinical significance of these indices in patients with
      soft tissue sarcoma (STS). Seven hundred and twelve patients with available blood
      counts at diagnosis and/or metastatic relapse were retrospectively examined. An
      optimal cutoff for NLR-high (>2.5) in predicting overall survival (OS) was
      determined using receiver operating curve analyses. Survival analyses were
      performed using the Kaplan-Meier method and multivariate Cox proportional models.
      Our results show that NLR was significantly higher in patients with distant
      metastasis at diagnosis (n = 183) compared to those without (n = 529) (median:
      4.36 vs 2.85, p < 0.0001). Progression of localized disease at diagnosis to
      metastatic relapse within the same patients was associated with an interval
      increase in NLR (median: 3.21 vs 3.74, p = 0.0003). In multivariate analysis, NLR
      high was the only consistent factor independently associated with both worse OS
      (HR 1.53, 95% CI 1.10-2.13, p = 0.0112) and relapse-free survival (HR 1.41, 95%
      CI 1.08-1.85, p = 0.0125) in localized disease, as well as OS (HR 1.82, 95% CI
      1.16-2.85, p = 0.0087) in metastatic/unresectable disease. In conclusion, high
      NLR is an independent marker of poor prognosis among patients with STS.

PMID- 30097599
TI  - Autophagy upregulation as a possible mechanism of arsenic induced diabetes.
AB  - The key features of type 2 diabetes mellitus (T2DM) caused by high fat diet (HFD)
      in combination with arsenic (As) exposure (pronounced glucose intolerance despite
      a significant decrease in insulin resistance) are different from those expected
      for T2DM. Autophagy has been considered as a possible link between insulin
      resistance and obesity. Therefore in this study, we utilized autophagy gene
      expression profiling via real-time RT-PCR array analysis in livers of NMRI mice
      exposed to an environmentally relevant and minimally cytotoxic concentration of
      arsenite (50 ppm) in drinking water while being fed with a HFD for 20 weeks. Out
      of 84 genes associated with autophagy under study, 21 genes were related to
      autophagy machinery components of which 13 genes were downregulated when HDF diet
      was applied. In this study, for the first time, it was shown that the exposure to
      arsenic in the livers of mice chronically fed with HFD along with increased
      oxidative stress resulted in the restoration of autophagy [upregulation of genes
      involved in the early phase of phagophore formation, phagophore expansion and
      autophagosome-lysosome linkage stages]. Considering the role of arsenic in the
      induction of autophagy; it can be argued that reduced insulin resistance in HFD -
      As induced diabetes may be mediated by autophagy upregulation.

PMID- 30097601
TI  - Comparative transcriptomic profiling of peripheral efferent and afferent nerve
      fibres at different developmental stages in mice.
AB  - Peripheral nerve injury impairs motor and sensory function in humans, and its
      functional recovery largely depends on the axonal outgrowth required for the
      accurate reinnervation of appropriate targets. To better understand how motor and
      sensory nerve fibres select their terminal pathways, an unbiased cDNA microarray
      analysis was conducted to examine differential gene expression patterns in
      peripheral efferent and afferent fibres at different developmental stages in
      mice. Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG)
      analyses revealed common and distinct features of enrichment for differentially
      expressed genes during motor and sensory nerve fibre development. Ingenuity
      Pathway Analysis (IPA) further indicated that the key differentially expressed
      genes were associated with trans-synaptic neurexin-neuroligin signalling
      components and a variety of gamma-aminobutyric acid (GABA) receptors. The aim of
      this study was to generate a framework of gene networks regulated during motor
      and sensory neuron differentiation/maturation. These data may provide new clues
      regarding the underlying cellular and molecular mechanisms that determine the
      intrinsic capacity of neurons to regenerate after peripheral nerve injury. Our
      findings may thus facilitate further development of a potential intervention to
      manipulate the therapeutic efficiency of peripheral nerve repair in the clinic.

PMID- 30097602
TI  - Anomalously high value of Coulomb pseudopotential for the H5S2 superconductor.
AB  - The H5S2 and H2S compounds are the two candidates for the low-temperature phase
      of compressed sulfur-hydrogen system. We have shown that the value of Coulomb
      pseudopotential (MU*) for H5S2 ([TC]exp = 36 K and p = 112 GPa) is anomalously
      high. The numerical results give the limitation from below to MU* that is equal
      to 0.402 (MU* = 0.589), if we consider the first order vertex corrections to the
      electron-phonon interaction). Presented data mean that the properties of
      superconducting phase in the H5S2 compound can be understood within the classical
      framework of Eliashberg formalism only at the phenomenological level (MU* is the
      parameter of matching the theory to the experimental data). On the other hand, in
      the case of H2S it is not necessary to take high value of Coulomb pseudopotential
      to reproduce the experimental critical temperature relatively well (MU* = 0.15).
      In our opinion, H2S is mainly responsible for the observed superconductivity
      state in the sulfur-hydrogen system at low temperature.

PMID- 30097603
TI  - Cortical signatures of wakeful somatosensory processing.
AB  - Sensory inputs carry critical information for the survival of an organism. In
      mice, tactile information conveyed by the whiskers is of high behavioural
      relevance, and is broadcasted across cortical areas beyond the primary
      somatosensory cortex. Mesoscopic voltage sensitive dye imaging (VSDI) of cortical
      population response to whisker stimulations has shown that seemingly 'simple'
      sensory stimuli can have extended impact on cortical circuit dynamics. Here we
      took advantage of genetically encoded voltage indicators (GEVIs) that allow for
      cell type-specific monitoring of population voltage dynamics in a chronic dual
      hemisphere transcranial windowed mouse preparation to directly compare the cortex
      wide broadcasting of sensory information in wakening (lightly anesthetized to
      sedated) and awake mice. Somatosensory-evoked cortex-wide dynamics is altered
      across brain states, with anatomically sequential hyperpolarising activity
      observed in the awake cortex. GEVI imaging revealed cortical activity maps with
      increased specificity, high spatial coverage, and at the timescale of cortical
      information processing.

PMID- 30097605
TI  - Hairy root induction and benzylisoquinoline alkaloid production in Macleaya
      cordata.
AB  - Sanguinarine is currently widely used to replace antibiotic growth promoters in
      animal feeding and has demonstrated useful anticancer activity. Currently, the
      main source of sanguinarine is from an important medicinal plant, Macleaya
      cordata. To obtain a new source of sanguinarine production, we established hairy
      root cultures of M. cordata by co-cultivating leaf and stem explants with
      Agrobacterium rhizogenes. Except the co-cultivation medium, all growth media
      contained 200 mg/L timentin to eliminate A. rhizogenes. Through comparing the
      metabolic profiles and gene expression of hairy roots and wild-type roots sampled
      at five time points, we found that the sanguinarine and dihydrosanguinarine
      contents of hairy roots were far higher than those of wild-type roots, and we
      revealed the molecular mechanism that causes these metabolites to increase.
      Consequently, this study demonstrated that the hairy root system has further
      potential for bioengineering and sustainable production of sanguinarine on a
      commercial scale. To the best of our knowledge, this is the first efficient
      protocol reported for the establishment of hairy root cultures in M. cordata
      using A. rhizogenes.

PMID- 30097604
TI  - Magnetic map navigation in a migratory songbird requires trigeminal input.
AB  - Recently, virtual magnetic displacement experiments have shown that magnetic cues
      are indeed important for determining position in migratory birds; but which
      sensory system(s) do they use to detect the magnetic map cues? Here, we show that
      Eurasian reed warblers need trigeminal input to detect that they have been
      virtually magnetically displaced. Birds with bilaterally ablated ophthalmic
      branches of the trigeminal nerves were not able to re-orient towards their
      conspecific breeding grounds after a virtual magnetic displacement, exactly like
      they were not able to compensate for a real physical displacement. In contrast,
      sham-operated reed warblers re-oriented after the virtual displacement, like
      intact controls did in the past. Our results show that trigeminally mediated
      sensory information is necessary for the correct function of the reed warblers'
      magnetic positioning system.

PMID- 30097606
TI  - Identification of UAP1L1 as a critical factor for protein O-GlcNAcylation and
      cell proliferation in human hepatoma cells.
AB  - Aged hepatocyte-specific-Mcl-1 knockout (MKO-hep) mice are prone to develop liver
      tumors mimicking human hepatocellular carcinoma (HCC). Here we reported that a
      protein named UDP-N-acetylglucosamine pyrophosphorylase-1-like-1 (Uap1l1) is
      upregulated in the liver of young MKO-hep mice without any macroscopically
      detectable tumor nodules and is prominently expressed in the hepatic tumors
      developed in the aged MKO-hep mice. Intriguingly, human UAP1L1 is also
      significantly upregulated in a distinct subset of HCC tissues and patients with
      upregulated expression of UAP1L1 appeared to have poor prognosis. Overexpression
      of UAP1L1 significantly promoted, whereas UAP1L1 knockdown markedly reduced the
      proliferation of human hepatoma cells both in vitro and in vivo. UAP1L1 shows
      ~59% sequence identity to UDP-N-acetylglucosamine pyrophosphorylase-1 (UAP1),
      which is directly involved in the synthesis of the sugar donor (UDP-GlcNac) for N
      acetylglucosamine modification (O-GlcNAcylation) of proteins. However, unlike
      UAP1, UAP1L1 harbors very limited UDP-GlcNAc synthesis activity. Moreover,
      although both UAP1 and UAP1L1 are required for O-GlcNAc transferase (OGT)
      mediated protein O-GlcNAcylation, they appear to function distinctly from each
      other. UAP1L1 directly interacts with OGT, but does not seem to be an OGT
      substrate. In addition, UAP1L1 alone is not sufficient to activate OGT activity
      in vitro, suggesting that UAP1L1 may function together with other proteins to
      modulate OGT activity in vivo. Lastly, UAP1L1 knockdown attenuated c-MYC O
      GlcNAcylation and protein stability, and overexpression of c-MYC significantly
      rescued the proliferation defect of UAP1L1 knockdown HepG2 cells, suggesting that
      c-MYC is one downstream target of UAP1L1 that contributes to UAP1L1-mediated cell
      proliferation, at least in HepG2 cells.

PMID- 30097608
TI  - A Recombinant Newcastle Disease Virus (NDV) Expressing S Protein of Infectious
      Bronchitis Virus (IBV) Protects Chickens against IBV and NDV.
AB  - Infectious bronchitis virus (IBV) causes a highly contagious respiratory,
      reproductive and urogenital tract disease in chickens worldwide, resulting in
      substantial economic losses for the poultry industry. Currently, live-attenuated
      IBV vaccines are used to control the disease. However, safety, attenuation and
      immunization outcomes of current vaccines are not guaranteed. Several studies
      indicate that attenuated IBV vaccine strains contribute to the emergence of
      variant viruses in the field due to mutations and recombination. Therefore, there
      is a need to develop a stable and safe IBV vaccine that will not create variant
      viruses. In this study, we generated recombinant Newcastle disease viruses
      (rNDVs) expressing the S1, S2 and S proteins of IBV using reverse genetics
      technology. Our results showed that the rNDV expressing the S protein of IBV
      provided better protection than the rNDV expressing S1 or S2 protein of IBV,
      indicating that the S protein is the best protective antigen of IBV. Immunization
      of 4-week-old SPF chickens with the rNDV expressing S protein elicited IBV
      specific neutralizing antibodies and provided complete protection against
      virulent IBV and virulent NDV challenges. These results suggest that the rNDV
      expressing the S protein of IBV is a safe and effective bivalent vaccine
      candidate for both IBV and NDV.

PMID- 30097607
TI  - Combined quantification of procalcitonin and HLA-DR improves sepsis detection in
      surgical patients.
AB  - Early recognition of sepsis is a key factor to improve survival to this disease
      in surgical patients, since it allows prompt control of the infectious source.
      Combining pro-inflammatory and immunosupression biomarkers could represent a good
      strategy to improve sepsis detection. Here we evaluated the combination of
      procalcitonin (PCT) with gene expression levels of HLA-DRA to detect sepsis in a
      cohort of 154 surgical patients (101 with sepsis and 53 with no infection). HLA
      DRA expression was quantified using droplet digital PCR, a next-generation PCR
      technology. Area under the receiver operating curve analysis (AUROC) showed that
      the PCT/HLA-DRA ratio outperformed PCT to detect sepsis (AUROC [CI95%], p): PCT:
      0.80 [0.73-0.88], <0.001; PCT/HLA-DRA: 0.85 [0.78-0.91], <0.001. In the
      multivariate analysis, the ratio showed a superior ability to predict sepsis
      compared to that of PCT (OR [CI 95%], p): PCT/HLA-DRA: 7.66 [1.82-32.29], 0.006;
      PCT: 4.21 [1.15-15.43] 0.030. Multivariate analysis was confirmed using a new
      surgical cohort with 74 sepsis patients and 21 controls: PCT/HLA-DRA: 34.86 [1.22
      995.08], 0.038; PCT: 5.52 [0.40-75.78], 0.201. In conclusion, the combination of
      PCT with HLA-DRA is a promising strategy for improving sepsis detection in
      surgical patients.

PMID- 30097609
TI  - Effect of patterned polyacrylamide hydrogel on morphology and orientation of
      cultured NRVMs.
AB  - We recently demonstrated that patterned Parylene C films could be effectively
      used as a mask for directly copolymerizing proteins on polyacrylamide hydrogel
      (PAm). In this work, we have proved the applicability of this technique for
      studying the effect such platforms render on neonatal rat ventricular myocytes
      (NRVMs). Firstly, we have characterised topographically and mechanically the
      scaffolds in liquid at the nano-scale level. We thus establish that such
      platforms have physical properties that closely mimics the in vivo extracellular
      environment of cells. We have then studied the cell morphology and physiology by
      comparing cultures on flat uniformly-covered and collagen-patterned scaffolds. We
      show that micro-patterns promote the elongation of cells along the principal axis
      of the ridges coated with collagen. In several cases, cells also tend to create
      bridges across the grooves. We have finally studied cell contraction, monitoring
      Ca2+ cycling at a certain stimulation. Cells seeded on patterned scaffolds
      present significant responses in comparison to the isotropic ones.

PMID- 30097610
TI  - On detection of periodicity in C-reactive protein (CRP) levels.
AB  - C-reactive protein (CRP) is an acute-phase plasma protein that can be used as a
      biomarker for activation of the immune system. A spectral analysis of CRP level
      over time for patients with gynaecological tumours has been reported by Madondo
      et al., using a periodogram method, suggesting that there is no significant
      periodicity in the data. In our study, we investigate the impact of low sample
      number on periodogram analysis, for non-uniform sampling intervals-we conclude
      that data of Madondo et al. cannot rule out periodic behaviour. The search for
      patterns (periodic or otherwise) in the CRP time-series is of interest for
      providing a cue for the optimal times at which cancer therapies are best
      administered. In this paper we show (i) there is no evidence to rule out
      periodicity in CRP levels, and (ii) we provide a prescription for the minimum
      data sample rate required in future experiments for improved testing of a
      periodic CRP signal hypothesis. The analysis we provide may be used for
      establishing periodicity in any short time-series signal that is observed without
      a priori information.

PMID- 30097612
TI  - Should suicide prevention training be required for mental health practitioners? A
      Colorado, United States case study.
AB  - Suicide is a critical public health problem, resulting in more than 40,000 deaths
      a year in the United States (U.S.) and 800,000 globally. Provision of mental
      health services is a key component of a comprehensive population-based approach
      to prevention. State licensing boards in some U.S. states require mental health
      practitioners to be trained in suicide risk assessment and management, but such
      requirements are not uniform. Our case study examined mental health practitioner
      preparedness to engage in suicide prevention and intervention in Colorado, a
      state with a high suicide rate, using a survey designed to understand training
      experiences and perceptions of the acceptability of mandated training. Our
      findings support efforts to require mental health practitioners be trained to
      prevent suicide.

PMID- 30097611
TI  - Correction: "Congenital hyperinsulinism as the presenting feature of Kabuki
      syndrome: clinical and molecular characterization of 10 affected individuals".
AB  - The author Diva D. De Leon was incorrectly listed as instead of Diva D. De Leo
      Critchlow in the original version of this paper.

PMID- 30097613
TI  - Diabetic complication could get a gene therapy boost.

PMID- 30097614
TI  - Nutrient scavenging in cancer.
AB  - While cancer cell proliferation depends on access to extracellular nutrients,
      inadequate tumour perfusion means that glucose, amino acids and lipids are often
      in short supply. To overcome this obstacle to growth, cancer cells utilize
      multiple scavenging strategies, obtaining macromolecules from the
      microenvironment and breaking them down in the lysosome to produce substrates for
      ATP generation and anabolism. Recent studies have revealed four scavenging
      pathways that support cancer cell proliferation in low-nutrient environments:
      scavenging of extracellular matrix proteins via integrins, receptor-mediated
      albumin uptake and catabolism, macropinocytic consumption of multiple components
      of the tumour microenvironment and the engulfment and degradation of entire live
      cells via entosis. New evidence suggests that blocking these pathways alone or in
      combination could provide substantial benefits to patients with incurable solid
      tumours. Both US Food and Drug Administration (FDA)-approved drugs and several
      agents in preclinical or clinical development shut down individual or multiple
      scavenging pathways. These therapies may increase the extent and durability of
      tumour growth inhibition and/or prevent the development of resistance when used
      in combination with existing treatments. This Review summarizes the evidence
      suggesting that scavenging pathways drive tumour growth, highlights recent
      advances that define the oncogenic signal transduction pathways that regulate
      scavenging and considers the benefits and detriments of therapeutic strategies
      targeting scavenging that are currently under development.

PMID- 30097617
TI  - On the loss of human sex chromosomes in lymphocytes with age: a quantitative
      treatment.
AB  - Increasing levels of aneuploidy of the sex chromosomes in human lymphocytes with
      age have been noted for several decades. The percentage of chromosome Y loss can
      reach up to 1.5% or even more, whereas the levels of X0 cells in females can
      increase up to 5% with age. Here, I propose simple mathematical models of the
      dynamics of 'normal' sex chromosome loss with age. These exponential models
      provide more mechanistic insights than linear regressions. They account for the
      lower incidence of sex chromosome loss in young individuals and its increase with
      age. Moreover, the exponential models show that aneuploidy of the sex chromosomes
      provides a selective advantage. As there are no longitudinal data available (for
      the same individual at different time points), the parameters reported here are
      average values derived from a population. Hopefully, this study will stimulate
      further work based on next-generation technologies to obtain better estimates of
      sex chromosome aneuploidy and of the parameters of the models discussed here.

PMID- 30097616
TI  - Characterization of three ciliopathy pedigrees expands the phenotype associated
      with biallelic C2CD3 variants.
AB  - Whole exome sequencing (WES) is utilized in diagnostic odyssey cases to identify
      the underlying genetic cause associated with complex phenotypes. Recent
      publications suggest that WES reveals the genetic cause in ~25% of these cases
      and is most successful when applied to children with neurological disease. The
      residual 75% of cases remain genetically elusive until more information becomes
      available in the literature or functional studies are pursued. WES performed on
      three families with presumed ciliopathy diagnoses, including orofaciodigital
      (OFD) syndrome, fetal encephalocele, or Joubert-related disorder, identified
      compound heterozygous variants in C2CD3. Biallelic variants in C2CD3 have
      previously been associated with ciliopathies, including OFD syndrome type 14
      (OFD14; MIM: 615948). As three of the six identified variants were predicted to
      affect splicing, exon-skipping analysis using either RNA sequencing or PCR-based
      methods were completed to determine the pathogenicity of these variants, and
      showed that each of the splicing variants led to a frameshifted protein product.
      Using these studies in combination with the 2015 ACMG guidelines, each of the six
      identified variants were classified as either pathogenic or likely pathogenic,
      and are therefore likely responsible for our patients' phenotypes. Each of the
      families had a distinct clinical phenotype and severity of disease, extending
      from lethal to viable. These findings highlight that there is a broad phenotypic
      spectrum associated with C2CD3-mediated disease and not all patients present with
      the typical features of OFD14.

PMID- 30097615
TI  - Associative plasticity in supplementary motor area - motor cortex pathways in
      Tourette syndrome.
AB  - The important role of the supplementary motor area (SMA) in the generation of
      tics and urges in Gilles de la Tourette syndrome (GTS) is underscored by an
      increased SMA-motor cortex (M1) connectivity. However, whether plasticity is also
      altered in SMA-M1 pathways is unclear. We explored whether SMA-M1 plasticity is
      altered in patients with Tourette syndrome. 15 patients with GTS (mean age of
      33.4 years, SD = 9.9) and 19 age and sex matched healthy controls were
      investigated with a paired association stimulation (PAS) protocol using three
      transcranial magnetic stimulation (TMS) coils stimulating both M1 and the SMA.
      Standard clinical measures for GTS symptoms were collected. There was a
      significant PAS effect showing that MEP amplitudes measured in blocks during and
      after PAS were significantly higher compared to those in the first block.
      However, the degree of PAS was not differentially modulated between patients and
      controls as shown by a Bayesian data analysis. PAS effects in GTS correlated
      positively with the YGTSS motor tic severity. Plasticity previously reported to
      be altered in sensorimotor pathways in GTS is normal in SMA-M1 projections
      suggesting that the dysfunction of the SMA in GTS is not primarily related to
      altered plasticity in SMA-M1 connections.

PMID- 30097619
TI  - Author Correction: Dual-organ invasion is associated with a lower survival rate
      than single-organ invasion in distal bile duct cancer: A multicenter study.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30097618
TI  - Enzyme-modified non-oxidized LDL (ELDL) induces human coronary artery smooth
      muscle cell transformation to a migratory and osteoblast-like phenotype.
AB  - Enzyme modified non-oxidative LDL (ELDL) is effectively taken up by vascular
      smooth muscle cells (SMC) and mediates transition into foam cells and produces
      phenotypic changes in SMC function. Our data show that incubation of human
      coronary artery SMC (HCASMC) with low concentration of ELDL (10 MUg/ml) results
      in significantly enhanced foam cell formation compared to oxidized LDL (200
      MUg/ml; p < 0.01) or native LDL (200 MUg/ml; p < 0.01). Bioinformatic network
      analysis identified activation of p38 MAPK, NFkB, ERK as top canonical pathways
      relevant for biological processes linked to cell migration and osteoblastic
      differentiation in ELDL-treated cells. Functional studies confirmed increased
      migration of HCASMC upon stimulation with ELDL (10 MUg/ml) or Angiopoietin like
      protein 4, (ANGPTL4, 5 MUg/ml), and gain in osteoblastic gene profile with
      significant increase in mRNA levels for DMP-1, ALPL, RUNX2, OPN/SPP1,
      osterix/SP7, BMP and reduction in mRNA for MGP and ENPP1. Enhanced calcification
      of HCASMC by ELDL was demonstrated by Alizarin Red staining. In summary, ELDL is
      highly potent in inducing foam cells in HCASMC and mediates a phenotypic switch
      with enhanced migration and osteoblastic gene profile. These results point to the
      potential of ELDL to induce migratory and osteoblastic effects in human smooth
      muscle cells with potential implications for migration and calcification of SMCs
      in human atherosclerosis.

PMID- 30097620
TI  - BCS thermal vacuum of fermionic superfluids and its perturbation theory.
AB  - The thermal field theory is applied to fermionic superfluids by doubling the
      degrees of freedom of the BCS theory. We construct the two-mode states and the
      corresponding Bogoliubov transformation to obtain the BCS thermal vacuum. The
      expectation values with respect to the BCS thermal vacuum produce the statistical
      average of the thermodynamic quantities. The BCS thermal vacuum allows a quantum
      mechanical perturbation theory with the BCS theory serving as the unperturbed
      state. We evaluate the leading-order corrections to the order parameter and other
      physical quantities from the perturbation theory. A direct evaluation of the
      pairing correlation as a function of temperature shows the pseudogap phenomenon,
      where the pairing persists when the order parameter vanishes, emerges from the
      perturbation theory. The correspondence between the thermal vacuum and
      purification of the density matrix allows a unitary transformation, and we found
      the geometric phase associated with the transformation in the parameter space.

PMID- 30097621
TI  - Accelerated pharmaceutical protein development with integrated cell free
      expression, purification, and bioconjugation.
AB  - The use of living cells for the synthesis of pharmaceutical proteins, though
      state-of-the-art, is hindered by its lengthy process comprising of many steps
      that may affect the protein's stability and activity. We aimed to integrate
      protein expression, purification, and bioconjugation in small volumes coupled
      with cell free protein synthesis for the target protein, ciliary neurotrophic
      factor. Split-intein mediated capture by use of capture peptides onto a solid
      surface was efficient at 89-93%. Proof-of-principle of light triggered release
      was compared to affinity chromatography (His6 fusion tag coupled with Ni-NTA).
      The latter was more efficient, but more time consuming. Light triggered release
      was clearly demonstrated. Moreover, we transferred biotin from the capture
      peptide to the target protein without further purification steps. Finally, the
      target protein was released in a buffer-volume and composition of our choice,
      omitting the need for protein concentration or changing the buffer. Split-intein
      mediated capture, protein trans splicing followed by light triggered release, and
      bioconjugation for proteins synthesized in cell free systems might be performed
      in an integrated workflow resulting in the fast production of the target protein.

PMID- 30097623
TI  - Genomic diversity in low-risk disease: present and future.

PMID- 30097622
TI  - Impact of cervical cancer on quality of life of women in Hubei, China.
AB  - We aimed to assess the quality of life (QOL) of the patients with cervical cancer
      after initial treatment, the factors affecting QOL and their clinical relevance.
      A total of 256 patients with cervical cancer who visited Zhongnan Hospital of
      Wuhan University from January 2017 to December 2017 were enrolled in this study.
      The European Organization for Research and Treatment of Cancer Quality of Life
      Questionnaire Core-30 item (EORTC QLQ-C30) and cervical cancer module (EORTC QLQ
      CX24) was used to assess the QOL of patients. More than half of the patients with
      cervical cancer reported an excellent QOL. Symptoms mostly experienced were
      insomnia, constipation, financial difficulties, and menopausal symptoms. Global
      QOL and social functioning were statistically associated with education level,
      occupation, the area of living, family income and treatment modality. Similarly,
      role functioning showed significant association with the stage of cancer,
      treatment modality and time since diagnosis. The rural area of living and poor
      economic status of the patients with cervical cancer has a negative impact on
      overall quality of life. Younger and educated patients are more worried about
      sexuality. Patients treated with multiple therapies had more problems with their
      QOL scales than patients treated with surgery only.

PMID- 30097626
TI  - Real time in situ x-ray diffraction study of the crystalline structure
      modification of Ba0.5Sr0.5TiO3 during the post-annealing.
AB  - We report about an in situ study of crystalline structural changes during thermal
      treatment of a Ba0.5Sr0.5TiO3 (BSTO) film grown on MgO. The study covers the
      complete cycle of heating, annealing and cooling and reveals simultaneous
      phenomena of phase transitions and strain evolution, which have been
      characterized by in situ 2D reciprocal space mapping (2D-RSM) using high
      resolution synchrotron x-ray diffraction in coplanar and grazing incidence
      geometries. In this way, temperature induced phase transformation from the BSTO2
      to the BSTO1 phase has been monitored and the appearance of a further crystalline
      phase was detected. Moreover, for both BSTO phases, transitions between in-plane
      compressive and tensile states have been determined during thermal treatment.
      Furthermore, a contraction of the out-of-plane lattice components has been
      observed during the annealing phase while the in-plane lattice components remain
      leading to the change of the residual in-plane strain towards tensile state. The
      in situ 2D-RSM findings provide valuable and versatile insights into strain
      engineering and structure modification upon thermal treatment.

PMID- 30097625
TI  - Dose-dependent reversal of KCC2 hypofunction and phenobarbital-resistant neonatal
      seizures by ANA12.
AB  - Neonatal seizures have an incidence of 3.5 per 1000 newborns; while hypoxic
      ischemic encephalopathy (HIE) accounts for 50-60% of cases, half are resistant to
      1st-line anti-seizure drugs such as phenobarbital (PB). Tyrosine receptor kinase
      B (TrkB) activation following ischemic injury is known to increase neuronal
      excitability by downregulation of K-Cl co-transporter 2 (KCC2); a neuronal
      chloride (Cl-) co-transporter. In this study, three graded doses of ANA12, a
      small-molecule selective TrkB antagonist, were tested in CD1 mice at P7 and P10
      following induction of neonatal ischemia by a unilateral carotid ligation. The PB
      loading dose remained the same in all treatment groups at both ages. Evaluation
      criteria for the anti-seizure efficacy of ANA12 were: (1) quantitative
      electroencephalographic (EEG) seizure burden and power, (2) rescue of post
      ischemic KCC2 and pKCC2-S940 downregulation and (3) reversal of TrkB pathway
      activation following ischemia. ANA12 significantly rescued PB resistant seizures
      in a dose-dependent manner at P7 and improved PB efficacy at P10. Additionally,
      female pups responded better to lower doses of ANA12 compared to males. ANA12
      significantly reversed post-ischemic KCC2 downregulation and TrkB pathway
      activation at P7 when PB alone was inefficacious. Rescuing KCC2 hypofunction may
      be critical for preventing emergence of refractory seizures.

PMID- 30097627
TI  - Dye-functionalized Sol-gel Matrix on Carbon Nanotubes for Refreshable and
      Flexible Gas Sensors.
AB  - We report a colorimetric dye-functionalized sol-gel matrix on carbon nanotubes
      for use as a refreshable and flexible gas sensor with humidity calibration. Here,
      we fabricated gas sensors by functionalizing dye molecules on the top of carbon
      nanotube networks via a sol-gel method. Using hybrid gas sensors with different
      dye molecules, we could selectively detect various hazardous gases, such as NH3,
      Cl2 and SO2 gases, via optical and electrical signals. The sensors exhibited
      rather large conductance changes of more than 50% following exposure to gas
      species with concentrations even under the permissible exposure limit.
      Significantly, we could refresh used gas sensors by simply exposing them to fresh
      N2 gas without any heat treatment. Additionally, our sensors can be bent to form
      versatile practical sensor devices, such as tube-shape sensors for ventilation
      tubes. This work shows a simple but powerful method for building refreshable and
      selective gas sensors for versatile industrial and academic applications.

PMID- 30097628
TI  - Author Correction: The Significance of Interstitial Fibrosis on Left Ventricular
      Function in Hypertensive versus Hypertrophic Cardiomyopathy.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30097629
TI  - Tightly binding valence electron in aluminum observed through X-ray charge
      density study.
AB  - Accurate and high reciprocal resolution experimental structure factors of
      aluminum were determined from a synchrotron powder X-ray diffraction data
      measured at 30 K with sin theta/lambda < 2.31 A-1. The structure factors have
      small deviations from independent atom model in sin theta/lambda < 0.83 A-1.
      Theoretical structure factors were prepared using density functional theoretical
      calculations by full potential linearized augmented plane wave method. The
      deviation between experimental and theoretical data was also observed at around
      sin theta/lambda ~ 0.4 A-1. The charge density was determined by an extended
      Hansen-Coppens multipole modeling using experimental and theoretical structure
      factors. Charge density maxima at tetrahedral site were observed in both
      experimental and theoretical deformation density. The charge-density difference
      peaks indicating directional bonding formation were observed in the difference
      density between experiment and theory. The present study reveals tight binding
      like character of valence electron of aluminum. The fact will provide a crucial
      information for development of high-performance aluminum alloy.

PMID- 30097630
TI  - Pelvic organ prolapse and urogynecological assessment in women with spinal cord
      injury.
AB  - STUDY DESIGN: Observational cross-sectional study. OBJECTIVES: Due to weakened
      pelvic floor muscles, the risk of pelvic organ prolapse (POP) may increase after
      a spinal cord injury (SCI); hence, the aim of this study was to investigate the
      occurrence of POP after SCI and to evaluate the need for urogynecological
      consultations offered to women with SCI. SETTING: Clinic for Spinal Cord
      Injuries, Rigshospitalet, Denmark. METHODS: Women with SCI who visited our SCI
      clinic during January 2013-January 2018 were offered a specialized
      urogynecological consultation. Any symptoms of POP, urinary/fecal incontinence,
      or bladder/bowel emptying problems were registered, and POP was classified
      according to the POP quantification system during a pelvic examination.
      Differences in baseline characteristics between women with POP stage 0-1 and POP
      stage >=2 were investigated. RESULTS: A total of 98 women were included in the
      study. Fourteen women (14%) reported POP symptoms and 21 women (21%) had
      anatomical POP stage >=2. The group with POP stage >=2 had a significantly higher
      age, higher parity, more with vaginal delivery, and more postmenopausal women,
      but the groups did not differ on median time after injury, neurological level,
      and completeness of injury. A total of 71% experienced urinary incontinence, 27%
      experienced fecal incontinence, 63% experienced bladder emptying problems, and
      70% experienced bowel emptying problems. Consequently, 65% received treatment.
      CONCLUSIONS: Women with SCI are not in increased risk of developing anatomical
      POP. Nonetheless, the high occurrence of other urogynecological issues and the
      high treatment-rate supports the need for specialized urogynecological
      consultations offered to women with SCI.

PMID- 30097631
TI  - Thermoelectric properties of SnSe nanowires with different diameters.
AB  - Tin selenide (SnSe) has been the subject of great attention in the last years due
      to its highly efficient thermoelectricity and its possibilities as a green
      material, free of Pb and Te. Here, we report for the first time a
      thermoelectricity and transport study of individual SnSe micro- and nano-wires
      with diameters in the range between 130 nm and 1.15 MUm. X-ray diffraction and
      transmission electron microscopy analyses confirm an orthorhombic SnSe structure
      with Pnma (62) symmetry group and 1:1 Sn:Se atomic ratio. Electrical and thermal
      conductivity and the Seebeck coefficient were measured in each individual
      nanowire using a specialized suspended microdevice in the 150-370 K temperature
      range, yielding a thermal conductivity of 0.55 Wm-1 K-1 at room temperature and
      ZT ~ 0.156 at 370 K for the 130 nm diameter nanowire. The measured properties
      were correlated with electronic information obtained by model simulations and
      with phonon scattering analysis. The results confirm these structures as
      promising building blocks to develop efficient temperature sensors, refrigerators
      and thermoelectric energy converters. The thermoelectric response of the
      nanowires is compared with recent reports on crystalline, polycrystalline and
      layered bulk structures.

PMID- 30097632
TI  - Rapid and reversible impairment of episodic memory by a high-fat diet in mice.
AB  - Alzheimer's disease is a leading cause of morbidity and mortality with no cure
      and only limited treatment available. Obesity and type 2 diabetes are positively
      associated with the development of premature cognitive decline and Alzheimer's
      disease, linking diet with these conditions. Here we demonstrate that in mice
      episodic memory, together with spatial and contextual associative memory, is
      compromised after only one day of high-fat diet. However, object memory remains
      intact. This shows not only a more rapid effect than previously reported but also
      that more complex memories are at higher risk of being compromised by a high-fat
      diet. In addition, we show that these memory deficits are rapidly reversed by
      switching mice from a high-fat diet back to a low-fat diet. These findings have
      important implications for the contribution of nutrition to the development of
      cognitive decline and Alzheimer's disease.

PMID- 30097633
TI  - Time trends in stroke incidence and in prevalence of risk factors in Southern
      Germany, 1989 to 2008/09.
AB  - In prior studies, stroke incidence has mainly shown either declining time trends
      or stable rates in high-income countries. Changes could partially be linked to
      trends in classic cardiovascular disease (CVD) risk factors. In the present
      study, we analyzed the incidence of stroke in parallel with the prevalence of CVD
      risk factors over time in a German population. Data from three independent
      population-based MONICA/KORA Augsburg surveys conducted in 1989/90 (S2), 1994/95
      (S3), and 1999/2001 (S4) were used to calculate age-standardized incidence rates
      (IR) of first-ever stroke over eight years from each baseline survey.
      Furthermore, the age-standardized prevalence rates of CVD risk factors were
      analyzed for these surveys. Changes in IR or prevalence were considered
      significantly different if their 95% confidence intervals (CI) did not overlap.
      The age-standardized IR of stroke showed no significant time trend (S2: IR =
      203.4 per 100,000 person-years; CI 176.4-233.4, S3: IR = 225.6; 197.1-257.0, S4:
      IR = 209.9; CI 182.4-240.3). In agreement, the prevalence of the CVD risk factors
      was quite stable over time, showing divergent, but mostly non-significant
      changes. However, due to the aging Western societies and the longer survival time
      of stroke patients, the total number of stroke patients in the population will
      increase even with a stable IR.

PMID- 30097634
TI  - Effect of carbon black addition on thermal stability and capacitive performances
      of supercapacitors.
AB  - In this study, we propose a simple way to improve thermal stability of solid
      state supercapacitors (SCs) by adding carbon black (CB) into reduced graphene
      oxide (rGO) electrodes. The CB used as a heat-resistant additive contributes to
      stable operation of the rGO-CB SC even after 1000 charge/discharge cycles at 90 
      degrees C. In the case of the rGO SC without CB, it fails after the 166th cycles
      at 90  degrees C. Compared with the rGO SC, the rGO-CB SC exhibits the decrease
      in internal resistance from 42 to 18 Omega and the increase in specific
      capacitance from 115 to 160 F/g. Moreover, the rGO-CB SC shows a smaller
      variation in specific capacitance (12%) than that of rGO SC (30%) as the
      temperature increases from 30 to 90  degrees C. The observation reveals that the
      addition of CB being a heat-resistant additive helps improve performance of
      thermal stable SCs.

PMID- 30097635
TI  - Hypoalbuminemia as a predictor of acute kidney injury during colistin treatment.
AB  - This study aimed to assess the predictors of acute kidney injury (AKI) during
      colistin therapy in a cohort of patients with bloodstream infections (BSI) due to
      colistin-susceptible Gram-negative bacteria, focusing on the role of serum
      albumin levels. The study consisted of two parts: (1) a multicentre retrospective
      clinical study to assess the predictors of AKI during colistin therapy, defined
      according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria; and
      (2) bioinformatic and biochemical characterization of the possible interaction
      between human serum albumin and colistin. Among the 170 patients included in the
      study, 71 (42%), 35 (21%), and 11 (6%) developed KDIGO stage 1 (K1-AKI), KDIGO
      stage 2 (K2-AKI), and KDIGO stage 3 (K3-AKI), respectively. In multivariable
      analyses, serum albumin <2.5 g/dL was independently associated with K1-AKI
      (subdistribution hazard ratio [sHR] 1.85, 95% confidence interval [CI] 1.17-2.93,
      p = 0.009) and K2-AKI (sHR 2.37, 95% CI 1.15-4.87, p = 0.019). Bioinformatic and
      biochemical analyses provided additional information nurturing the discussion on
      how hypoalbuminemia favors development of AKI during colistin therapy. In
      conclusion, severe hypoalbuminemia independently predicted AKI during colistin
      therapy in a large cohort of patients with BSI due to colistin-susceptible Gram
      negative bacteria. Further study is needed to clarify the underlying causal
      pathways.

PMID- 30097637
TI  - Niche dissociated assembly drives insular lizard community organization.
AB  - Interspecific competition for resources leading to niche partitioning is
      considered as one of the major drivers of community assembly. Competitive niche
      partitioning is diagnosed from species co-occurrence, species abundance
      distributions (SADs), and body size distributions of species. For several
      decades, studies have explored these patterns for the relative significance of
      interspecific competition in shaping communities. We explored these patterns in a
      finite assemblage of insectivorous lizards in the Andaman & Nicobar Islands, both
      at the level of archipelago and individual islands. Negative geographic co
      occurrences occurred only between species pairs in islands separated by deep
      ocean channels. Ecologically similar species did not show positive co-occurrence
      in guild co-occurrence analyses, indicating that the negative geographical co
      occurrences between species in islands were due to historical allopatry. Species
      abundance distribution was best explained by a Pareto distribution in both
      metacommunity and local communities. There was no predictable spacing of body
      sizes among co-existing species in local communities. The empirical data on
      insular lizard community on species co-occurrence, SADs, and body size ratios
      does not lend support to assortment of species in islands caused by niche
      subdivision. Such niche-dissociated assembly of species in islands might be an
      important factor in formation of biological communities, regardless of geographic
      scale.

PMID- 30097638
TI  - An avian foundation for dominant tolerance.

PMID- 30097636
TI  - Tissue metabolite profiles for the characterisation of paediatric cerebellar
      tumours.
AB  - Paediatric brain tumors are becoming well characterized due to large genomic and
      epigenomic studies. Metabolomics is a powerful analytical approach aiding in the
      characterization of tumors. This study shows that common cerebellar tumors have
      metabolite profiles sufficiently different to build accurate, robust diagnostic
      classifiers, and that the metabolite profiles can be used to assess differences
      in metabolism between the tumors. Tissue metabolite profiles were obtained from
      cerebellar ependymoma (n = 18), medulloblastoma (n = 36), pilocytic astrocytoma
      (n = 24) and atypical teratoid/rhabdoid tumors (n = 5) samples using HR-MAS.
      Quantified metabolites accurately discriminated the tumors; classification
      accuracies were 94% for ependymoma and medulloblastoma and 92% for pilocytic
      astrocytoma. Using current intraoperative examination the diagnostic accuracy was
      72% for ependymoma, 90% for medulloblastoma and 89% for pilocytic astrocytoma.
      Elevated myo-inositol was characteristic of ependymoma whilst high taurine,
      phosphocholine and glycine distinguished medulloblastoma. Glutamine, hypotaurine
      and N-acetylaspartate (NAA) were increased in pilocytic astrocytoma. High lipids,
      phosphocholine and glutathione were important for separating ATRTs from
      medulloblastomas. This study demonstrates the ability of metabolic profiling by
      HR-MAS on small biopsy tissue samples to characterize these tumors. Analysis of
      tissue metabolite profiles has advantages in terms of minimal tissue pre
      processing, short data acquisition time giving the potential to be used as part
      of a rapid diagnostic work-up.

PMID- 30097639
TI  - Topological structures are consistently overestimated in functional complex
      networks.
AB  - Functional complex networks have meant a pivotal change in the way we understand
      complex systems, being the most outstanding one the human brain. These networks
      have classically been reconstructed using a frequentist approach that, while
      simple, completely disregards the uncertainty that derives from data finiteness.
      We provide here an alternative solution based on Bayesian inference, with link
      weights treated as random variables described by probability distributions, from
      which ensembles of networks are sampled. By using both statistical and
      topological considerations, we prove that the role played by links' uncertainty
      is equivalent to the introduction of a random rewiring, whose omission leads to a
      consistent overestimation of topological structures. We further show that this
      bias is enhanced in short time series, suggesting the existence of a theoretical
      time resolution limit for obtaining reliable structures. We also propose a simple
      sampling process for correcting topological values obtained in frequentist
      networks. We finally validate these concepts through synthetic and real network
      examples, the latter representing the brain electrical activity of a group of
      people during a cognitive task.

PMID- 30097642
TI  - Editorial Comment on "Utilization and Prescription Patterns of Phosphidiesterase
      5 Inhibitor Medications in the United States Military Health System".

PMID- 30097640
TI  - Impact of Body Mass Index on Oncological Outcomes of Prostate Cancer Patients
      after Radical Prostatectomy.
AB  - Obesity, often represented by higher body mass index (BMI), is not yet fully
      understood as a potential risk factor for poor clinical outcomes of prostate
      cancer (PCa) after radical prostatectomy (RP). This study aimed to evaluate the
      relationship between BMI and biochemical recurrence (BCR)-free survival in RP
      patients. This study retrospectively reviewed a total of 2.997 PCa patients who
      underwent RP between 2006 and 2017. The patients were stratified into three BMI
      groups according to the WHO recommendations for Asian men: normal weight (<23
      kg/m2), overweight (>=23 to <27.5 kg/m2) and obese (>=27.5 kg/m2). Multivariable
      logistic regression analyses were undertaken to evaluate the factors influencing
      the BCR rates including BMI. Multivariable Cox regression analyses and Kaplan
      Meier analyses were performed to test the association of obesity with BCR-free
      survival. The final pathologic results showed obese patients had greater positive
      surgical margin rates (13.9%, p < 0.001), extraprostatic invasion (19.9%, p <
      0.001), advanced pathological Gleason score (GS) >= 8 (50.8%, p = 0.017), and
      lymph node invasion (LNI) (14.5%, p = 0.021) than overweight and normal weight
      patients. According to Kaplan-Meier analyses, obese patients, especially with BMI
      >= 27.5, were more likely to have lower BCR-free-survival. Multivariate Cox
      analysis revealed that diabetes mellitus, LNI status, pT, pathologic GS,
      extraprostatic invasion, margin positivity and obesity with BMI >= 27.5 kg/m2
      were significantly associated with BCR-free survival after RP. Obesity (higher
      BMI) was significantly associated with BCR after RP. BMI >= 27.5 kg/m2 was an
      independent predictor of BCR-free survival.

PMID- 30097641
TI  - IPL-M1 interaction shapes pre-reflective social differentiation in the human
      action system: new insights from TBS and TMS combined.
AB  - The conscious experience of being the author of our own actions is thought to be
      grounded in pre-reflective and low-level sensorimotor representations of the self
      as different from the other. It has been suggested that the inferior parietal
      lobe (IPL) is generally involved in self-other differentiation processes and in
      providing an explicit sense of action authorship. However, direct evidence for
      its causal and functional role in distinguishing self-related and other-related
      sensorimotor representations is lacking. The current study employed theta-burst
      stimulation (TBS) to condition left IPL's activity before a social version of the
      rubber hand illusion led participants to illusorily attribute observed finger
      movements to their own body. We recorded motor evoked potentials to single-pulse
      transcranial magnetic stimulation over the primary motor cortex (M1) as proxies
      of action authorship during action observation. The results showed that in a
      control condition (intermediate TBS over the left IPL) others' actions
      facilitated whereas self-attributed movements inhibited the motor system.
      Critically, continuous TBS disrupted this mismatch between self and other
      representations. This outcome provides direct evidence for the IPL's role in
      providing fundamental authorship signals for social differentiation in the human
      action system.

PMID- 30097643
TI  - Targeting Nucleotide Binding Domain of Multidrug Resistance-associated Protein-1
      (MRP1) for the Reversal of Multi Drug Resistance in Cancer.
AB  - Multidrug resistance (MDR) is the major cause, by which cancer cells expel the
      drugs out, developing a challenge against the current chemotherapeutic drugs
      regime. This mechanism is attributed to the over expression of ABC transporters
      like MRP1 on the surface of cells. Since nucleotide binding domains (NBD) of ABC
      transporters are the site of ATP binding and hydrolysis, thereby in this study we
      have targeted NBD1 of MRP1using molecular docking and molecular dynamic
      simulations (MDS). The compounds present in the FDA approved library were docked
      against NBD1 of the human multidrug resistance associated protein 1 (PDB ID:
      2CBZ). For the docking studies, Standard Precision and Extra Precision methods
      were employed. After the EP docking studies, ligands showed an extremely low
      docking score that was indicative of very high binding affinity of the ligands to
      the NBD. Apart from the low docking score, another short listing criterion in
      simulation studies was the interaction of incoming ligand with the desired
      conserved residues of NDB involved in ATP binding and hydrolysis. Based on these
      measures, potassium citrate (DB09125) and technetium Tc-99m medronate (DB09138)
      were chosen and subjected to 100 ns simulation studies. From the MDS study we
      concluded that between these two compounds, potassium citrate is a better
      candidate for targeting MRP1.

PMID- 30097644
TI  - Millennial soil retention of terrestrial organic matter deposited in the Bengal
      Fan.
AB  - The abundance of organic carbon (OC) in vegetation and soils (~2,600 PgC)
      compared to carbon in the atmosphere (~830 PgC) highlights the importance of
      terrestrial OC in global carbon budgets. The residence time of OC in continental
      reservoirs, which sets the rates of carbon exchange between land and atmosphere,
      represents a key uncertainty in global carbon cycle dynamics. Retention of
      terrestrial OC can also distort bulk OC- and biomarker-based paleorecords, yet
      continental storage timescales remain poorly quantified. Using "bomb" radiocarbon
      (14C) from thermonuclear weapons testing as a tracer, we model leaf-wax fatty
      acid and bulk OC 14C signatures in a river-proximal marine sediment core from the
      Bay of Bengal in order to constrain OC storage timescales within the Ganges
      Brahmaputra (G-B) watershed. Our model shows that 79-83% of the leaf-waxes in
      this core were stored in continental reservoirs for an average of 1,000-1,200
      calendar years, while the remainder was stored for an average of 15 years. This
      age structure distorts high-resolution organic paleorecords across geologically
      rapid events, highlighting that compound-specific proxy approaches must consider
      storage timescales. Furthermore, these results show that future environmental
      change could destabilize large stores of old - yet reactive - OC currently stored
      in tropical basins.

PMID- 30097645
TI  - Fast Na ion transport triggered by rapid ion exchange on local length scales.
AB  - The realization of green and economically friendly energy storage systems needs
      materials with outstanding properties. Future batteries based on Na as an
      abundant element take advantage of non-flammable ceramic electrolytes with very
      high conductivities. Na3Zr2(SiO4)2PO4-type superionic conductors are expected to
      pave the way for inherently safe and sustainable all-solid-state batteries. So
      far, only little information has been extracted from spectroscopic measurements
      to clarify the origins of fast ionic hopping on the atomic length scale. Here we
      combined broadband conductivity spectroscopy and nuclear magnetic resonance (NMR)
      relaxation to study Na ion dynamics from the um to the angstrom length scale.
      Spin-lattice relaxation NMR revealed a very fast Na ion exchange process in
      Na3.4Sc0.4Zr1.6(SiO4)2PO4 that is characterized by an unprecedentedly high self
      diffusion coefficient of 9 * 10-12 m2s-1 at -10  degrees C. Thus, well below
      ambient temperature the Na ions have access to elementary diffusion processes
      with a mean residence time tauNMR of only 2 ns. The underlying asymmetric
      diffusion-induced NMR rate peak and the corresponding conductivity isotherms
      measured in the MHz range reveal correlated ionic motion. Obviously, local but
      extremely rapid Na+ jumps, involving especially the transition sites in Sc-NZSP,
      trigger long-range ion transport and push ionic conductivity up to 2 mS/cm at
      room temperature.

PMID- 30097646
TI  - The Springtime Influence of Natural Tropical Pacific Variability on the Surface
      Climate of the Ross Ice Shelf, West Antarctica: Implications for Ice Shelf
      Thinning.
AB  - Observational records starting in the 1950s show West Antarctica is amongst the
      most rapidly warming regions on the planet. Together with increased intrusions of
      warm circumpolar deep water (CDW) onto the continental shelf due to local wind
      forcing (the primary mechanism in recent decades), this has resulted in enhanced
      surface and basal melting of floating ice shelves and an associated acceleration
      and thinning of West Antarctic outlet glaciers, increasing the rate of global sea
      level rise. In this study, it is shown that during the austral spring season,
      significant surface warming across West Antarctica has shifted westward to the
      Ross Ice Shelf in recent decades in response to enhanced cyclonic circulation
      over the Ross Sea. These circulation changes are caused by a Rossby wave train
      forced by increasing sea surface temperatures in the western tropical Pacific,
      which is tied to the springtime shift of the Interdecadal Pacific Oscillation
      (IPO) to its negative phase after 1992. While the local wind trends enhance warm
      air advection and surface warming across the Ross Ice Shelf, the strong easterly
      component of the wind trends reduces the likelihood for intrusions of CDW onto
      the continental shelf in this region. This suggests that during spring there are
      competing mechanisms of surface and basal melting of the Ross Ice Shelf, both of
      which are closely tied to natural tropical Pacific decadal variability. Moreover,
      that the projected transition of the IPO back to its positive phase in the coming
      decade, though likely to reduce surface warming on the Ross Ice Shelf, could
      increase the risk of disintegration of Ross Sea ice shelves due to increased
      intrusions of CDW and enhanced basal melting.

PMID- 30097647
TI  - Archaeal biofilm formation.
AB  - Biofilms are structured and organized communities of microorganisms that
      represent one of the most successful forms of life on Earth. Bacterial biofilms
      have been studied in great detail, and many molecular details are known about the
      processes that govern bacterial biofilm formation, however, archaea are
      ubiquitous in almost all habitats on Earth and can also form biofilms. In recent
      years, insights have been gained into the development of archaeal biofilms, how
      archaea communicate to form biofilms and how the switch from a free-living
      lifestyle to a sessile lifestyle is regulated. In this Review, we explore the
      different stages of archaeal biofilm development and highlight similarities and
      differences between archaea and bacteria on a molecular level. We also consider
      the role of archaeal biofilms in industry and their use in different industrial
      processes.

PMID- 30097649
TI  - Crystal Ball: Walter Willett.

PMID- 30097650
TI  - Dietary calcium intake and hypertension risk: a dose-response meta-analysis of
      prospective cohort studies.
AB  - The association of calcium intake with risk of developing hypertension in the
      general population has not been established yet. We systematically searched
      PubMed and Scopus databases up to February 2018 to find prospective observational
      studies investigating the association of calcium intake with risk of developing
      hypertension. The reported risk estimates were pooled using a random-effects
      model. Eight prospective cohort studies (248,398 participants and 30,838 cases)
      were included. Seven studies measured dietary calcium intake, but one study
      measured total calcium intake (calcium from food and supplements). A significant
      inverse association was found for the highest versus lowest category of calcium
      intake (relative risk: 0.89, 95%CI: 0.86, 0.93; I2 = 0%, n = 8), and for each 500
      mg/d increment (relative risk: 0.93, 95%CI: 0.90, 0.97; I2 = 64%, n = 7). Summary
      results were the same with the main analyses when the analyses were restricted
      only to dietary calcium intake. A nonlinear dose-response meta-analysis exhibited
      a linear inverse association, with a somewhat steeper trend within the low and
      moderate intakes. In conclusion, higher dietary calcium intake, independent of
      adiposity and intake of other blood pressure-related minerals, is slightly
      associated with a lower risk of developing hypertension.

PMID- 30097648
TI  - Adenosine Kinase couples sensing of cellular potassium depletion to purine
      metabolism.
AB  - Adenosine Kinase (ADK) regulates the cellular levels of adenosine (ADO) by fine
      tuning its metabolic clearance. The transfer of gamma-phosphate from ATP to ADO
      by ADK involves regulation by the substrates and products, as well as by Mg2+ and
      inorganic phosphate. Here we present new crystal structures of mouse ADK (mADK)
      binary (mADK:ADO; 1.2 A) and ternary (mADK:ADO:ADP; 1.8 A) complexes. In
      accordance with the structural demonstration of ADO occupancy of the ATP binding
      site, kinetic studies confirmed a competitive model of auto-inhibition of ADK by
      ADO. In the ternary complex, a K+ ion is hexacoordinated between loops adjacent
      to the ATP binding site, where Asp310 connects the K+ coordination sphere to the
      ATP binding site through an anion hole structure. Nuclear Magnetic Resonance 2D
      15N-1H HSQC experiments revealed that the binding of K+ perturbs Asp310 and
      residues of adjacent helices 14 and 15, engaging a transition to a catalytically
      productive structure. Consistent with the structural data, the mutants D310A and
      D310P are catalytically deficient and loose responsiveness to K+. Saturation
      Transfer Difference spectra of ATPgammaS provided evidence for an unfavorable
      interaction of the mADK D310P mutant for ATP. Reductions in K+ concentration
      diminish, whereas increases enhance the in vitro activity of mADK (maximum of 2.5
      fold; apparent Kd = 10.4 mM). Mechanistically, K+ increases the catalytic
      turnover (Kcat) but does not affect the affinity of mADK for ADO or ATP.
      Depletion of intracellular K+ inhibited, while its restoration was accompanied by
      a full recovery of cellular ADK activity. Together, this novel dataset reveals
      the molecular basis of the allosteric activation of ADK by K+ and highlights the
      role of ADK in connecting depletion of intracellular K+ to the regulation of
      purine metabolism.

PMID- 30097651
TI  - Association between vitamin D deficiency and lipid and non-lipid markers of
      cardiovascular diseases in the middle east region.
AB  - BACKGROUND: Previous studies have associated vitamin D deficiency with
      cardiovascular disease (CVD) markers. The underlying mechanism remains elusive.
      Lipid and non-lipid markers of CVD and their relationship to vitamin D deficiency
      have not been assessed simultaneously. OBJECTIVE: To measure the association
      between vitamin D deficiency and non-lipid markers of CVD after adjustment of
      lipid markers. METHODS: This cross-sectional study used the following biological
      data, which was routinely collected in a general hospital laboratory database
      between 2011 and 2016: 25OH vitamin D [25(OH)D], creatinine, CKD-EPI eGFR (eGFR),
      fasting blood glucose (FPG), glycated hemoglobin (HbA1c), uric acid, gamma
      glutamyl transferase (gammaGT), C-reactive protein (CRP), total cholesterol, LDL
      cholesterol, HDL cholesterol, triglycerides, and a surrogate for CVD. Crude odds
      ratios (ORs) and ORs adjusted for lipid profile, gender and age using separate
      logistic regression models were derived. RESULTS: A total of 8658 subjects were
      included. Half had 25(OH)D < 20 ng/mL. 25(OH)D was associated with increased odds
      of CRP, eGFR, increased uric acid, gammaGT, FPG, HbA1c, male gender, CV status,
      and abnormal lipid markers. After adjustment for lipid markers, age, and gender,
      vitamin D deficiency was associated with increased odds of CRP, eGFR, gammaGT,
      FPG, HbA1c, and the surrogate for CVD. CONCLUSIONS: In this exploratory analysis,
      the first of its kind in the MENA region, vitamin D deficiency was associated
      with abnormal lipid markers, non-lipid markers of CVD, male gender, lower eGFR,
      and a surrogate variable for CVD. The association between vitamin D deficiency
      and non-lipid markers of CVD persisted after adjustment for lipid markers, age,
      and gender.

PMID- 30097652
TI  - Predictors for misreporting sodium and potassium intakes by overweight and obese
      participants in a food-based clinical trial: implications for practice.
AB  - This study compared self-reported sodium and potassium intakes with urinary
      biomarkers and identified predictive factors. Secondary analysis of the 3-month
      intensive phase of the HealthTrack study with control (C), interdisciplinary
      intervention (I), intervention plus 30 g walnuts/day (IW) arms (n = 149). Dietary
      data was derived from diet history (DH) interviews and biomarker measures from
      urine. Urine-derived sodium (all, p = 0.000) and potassium (C: p = 0.011; I: p =
      0.000; IW: p = 0.004) measures were significantly greater than self-reported
      intakes over the three months. Multiple linear regression showed body weight at
      baseline, body mass index (BMI) at baseline, and combined BMI at baseline and DH
      interviewer significantly negatively predicted the differences in sodium intake
      and excretion for C (beta = -21.226, p = 0.016), I (beta = -106.140, p = 0.002)
      and IW (F (9.530, 2df), p = 0.000), respectively. Where intakes of sodium and
      potassium are of interest in a trial, both reported intake and urinary biomarker
      measures are recommended.

PMID- 30097653
TI  - Response to Letter to Editor re: "Screening for pulmonary hypertension in preterm
      infants-not ready for prime time".

PMID- 30097654
TI  - Use of car beds for infant travel: a review of the literature.
AB  - Discharging neonates in a proper car safety seat is standard of care in the
      United States and many other countries. However, not every neonate can be safely
      positioned in a standard semi-upright car seat. In these cases, providers may opt
      for a travel device that allows the infant to lie flat, either supine or prone,
      known as a car bed. Minimal evidence exists to guide providers on car bed safety
      and help determine which infants would benefit from discharge in a car bed. In
      this article, we provide a comprehensive summary of existing literature on the
      safety of car beds for motor vehicle travel, car bed use in specific patient
      populations, and car beds vs. car seats for infants at risk of adverse
      cardiorespiratory events, including preterm infants with Hg-O2 desaturations in
      the car seat. We discuss recommendations for the follow-up of infants discharged
      in a car bed in order to safely transition back to a car seat.

PMID- 30097655
TI  - Birds perceive colours in categories.

PMID- 30097657
TI  - Profile of an unknown airway cell.

PMID- 30097656
TI  - Yeast chromosome numbers minimized using genome editing.

PMID- 30097658
TI  - Reaction combination opens up 3D molecular diversity for drug discovery.

PMID- 30097659
TI  - Author Correction: Synaptic N6-methyladenosine (m6A) epitranscriptome reveals
      functional partitioning of localized transcripts.
AB  - In the version of this article initially published, a Supplementary Fig. 6f was
      cited in the last paragraph of the Results. No such panel exists; the citation
      has been deleted. The error has been corrected in the HTML and PDF versions of
      the article.

PMID- 30097660
TI  - Author Correction: Stability of an adaptive hybrid community.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30097661
TI  - Single cell analysis reveals a biophysical aspect of collective cell-state
      transition in embryonic stem cell differentiation.
AB  - In the stem cell research field, the molecular regulatory network used to define
      cellular states has been extensively studied, however, the general driving force
      guiding the collective state dynamics remains to be identified from biophysical
      aspects. Here we monitored the time-development of the cell-state transition at
      the single-cell and colony levels, simultaneously, during the early
      differentiation process in mouse embryonic stem cells. Our quantitative analyses
      revealed that cellular heterogeneity was a result of spontaneous fluctuation of
      cellular state and cell-cell cooperativity. We considered that the cell state is
      like a ball fluctuating on a potential landscape, and found that the
      cooperativity affects the fluctuation. Importantly, the cooperativity temporarily
      decreased and increased in the intermediate state of cell differentiation,
      leading to cell-state transition in unison. This process can be explained using
      the mathematical equation of flashing-ratchet behaviour, which suggests that a
      general mechanism is driving the collective decision-making of stem cells.

PMID- 30097662
TI  - Author Correction: Soy protein supplementation is not androgenic or estrogenic in
      college-aged men when combined with resistance exercise training.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30097663
TI  - Integrative analysis of fitness and metabolic effects of plasmids in Pseudomonas
      aeruginosa PAO1.
AB  - Horizontal gene transfer (HGT) mediated by the spread of plasmids fuels evolution
      in prokaryotes. Although plasmids provide bacteria with new adaptive genes, they
      also produce physiological alterations that often translate into a reduction in
      bacterial fitness. The fitness costs associated with plasmids represent an
      important limit to plasmid maintenance in bacterial communities, but their
      molecular origins remain largely unknown. In this work, we combine phenomics,
      transcriptomics and metabolomics to study the fitness effects produced by a
      collection of diverse plasmids in the opportunistic pathogen Pseudomonas
      aeruginosa PAO1. Using this approach, we scan the physiological changes imposed
      by plasmids and test the generality of some main mechanisms that have been
      proposed to explain the cost of HGT, including increased biosynthetic burden,
      reduced translational efficiency, and impaired chromosomal replication. Our
      results suggest that the fitness effects of plasmids have a complex origin, since
      none of these mechanisms could individually provide a general explanation for the
      cost of plasmid carriage. Interestingly, our results also showed that plasmids
      alter the expression of a common set of metabolic genes in PAO1, and produce
      convergent changes in host cell metabolism. These surprising results suggest that
      there is a common metabolic response to plasmids in P. aeruginosa PAO1.

PMID- 30097664
TI  - Distribution and population structure of endobacteria in arbuscular mycorrhizal
      fungi at North Atlantic dunes.
AB  - Arbuscular mycorrhizal fungi (AMF, Glomeromycotina), in addition to forming
      symbioses with the majority of land plants, harbor vertically transmitted
      endosymbiotic bacteria 'Candidatus Glomeribacter gigasporarum' (CaGg) and
      'Candidatus Moeniiplasma glomeromycotorum' (CaMg). CaGg is a nonessential
      mutualist of AMF, whereas the lifestyle of CaMg is unknown. To start unraveling
      the interactions between AMF and their endosymbionts in nature, we examined
      diversity and distribution of AMF-associated endobacteria in North Atlantic dunes
      at Cape Cod. Of nearly 500 foredune AMF isolates successfully genotyped during a
      systematic study, 94% were classified as Gigasporaceae. Two percent of all AMF
      spores harbored CaGg, and 88% contained CaMg. CaGg was found only in the
      Gigasporaceae, whereas CaMg was present in Gigasporaceae, Acaulosporaceae, and
      Diversisporaceae. Incidence of CaGg across AMF was not affected by any of the
      environmental parameters measured, whereas distribution of CaMg in one of the
      fungal hosts was impacted by plant density. CaMg populations associated with AMF
      individuals displayed high levels of genetic diversity but no evidence of gene
      flow, suggesting that host physical proximity is not sufficient to facilitate
      horizontal transmission of CaMg. Finally, in addition to a novel lineage of CaGg,
      we discovered that AMF likely harbor Burkholderia-related bacteria with close
      phylogenetic affinity to free-living Burkholderia and endobacteria of other
      Mucoromycota fungi.

PMID- 30097666
TI  - [Cold atmospheric plasma for the treatment of urological tumors].
AB  - Cold atmospheric plasma (CAP) is a highly reactive ionized physical state
      consisting of electrically charged particles, radicals and photons as well as
      electromagnetic radiation. Due to the high energy and reactivity of plasma
      components, physical plasmas are also referred to as the 4th aggregate state. In
      biological systems, CAP promotes antimicrobial, immunomodulatory, anti
      inflammatory, and wound-healing effects. Moreover, CAP bears antineoplastic
      properties which may be applied as a potential intraoperative option in the
      treatment of wound and resection margins during surgery of urological tumors.
      Some properties such as the penetration depth in various biological tissues, the
      effect on physiological healthy tissue, and the molecular mode of action
      regarding signalling and effector pathways are the subject of further
      investigation. CAP treatment effectively attenuates malignant cell growth. As an
      intraoperative application, CAP may represent a promising option particularly for
      the treatment of tissue regions that are close to critical structures (e. g.,
      nerves, adjacent organs). The present review article summarizes the current
      status of CAP-related studies in the field of urological oncology.

PMID- 30097665
TI  - Temperature-dependent excitonic superuid plasma frequency evolution in an
      excitonic insulator, Ta2NiSe5.
AB  - An interesting van der Waals material, Ta2NiSe5 has been known one of strong
      excitonic insulator candidates since it has very small or zero bandgap and can
      have a strong exciton binding energy because of its quasi-one-dimensional crystal
      structure. Here we investigate a single crystal Ta2NiSe5 using optical
      spectroscopy. Ta2NiSe5 has quasi-one-dimensional chains along the a-axis. We have
      obtained anisotropic optical properties of a single crystal Ta2NiSe5 along the a-
      and c-axes. The measured a- and c-axis optical conductivities exhibit large
      anisotropic electronic and phononic properties. With regard to the a-axis optical
      conductivity, a sharp peak near 3050 cm-1 at 9 K, with a well-defined optical gap
      ([Formula: see text] 1800 cm-1) and a strong temperature-dependence, is observed.
      With an increase in temperature, this peak broadens and the optical energy gap
      closes around ~325 K ([Formula: see text]). The spectral weight redistribution
      with respect to the frequency and temperature indicates that the normalized
      optical energy gap ([Formula: see text]) is [Formula: see text]. The temperature
      dependent superfluid plasma frequency of the excitonic condensation in Ta2NiSe5
      has been determined from measured optical data. Our study may pave new avenues in
      the future research on excitonic insulators.

PMID- 30097667
TI  - Profile and outcome of patients with recurrent urogenital fistula in a fistula
      centre in Nigeria.
AB  - INTRODUCTION AND HYPOTHESIS: Management of a recurrent urogenital fistula is very
      challenging and requires experienced surgeons. The aim of this study was to
      describe the characteristics, success rates, and associated factors related to
      surgical repairs of patients with recurrent urogenital fistulas by an experienced
      team at a fistula centre in Nigeria. METHODS: This was a retrospective cohort
      study of 154 patients that had repeat urogenital fistula repairs at the National
      Obstetric Fistula Centre, Abakaliki, Nigeria, between January 2014 and December
      2016. Information was retrieved from their hospital records. Successful repair
      was defined by continent status at 3 months after repair. Data were analyzed with
      SPSS version 20 by IBM Inc., and p < 0.05 was taken as statistically significant.
      Chi-square test was used to determine the association between the factors and
      successful repair. RESULTS: The mean age was 36.27 +/- 12.96 years. Obstetric
      fistula occurred in 92.2% of the patients. The success rates for the first,
      second, third, and fourth repeat repairs were 68.8%. 56.2%, 50%, and 0%
      respectively. Significant factors were the number of previous attempts at repair
      (chi2 = 20.44, p = 0.002), age group (chi2 = 16.95, p = 0.03), Waaldijk's
      classification (chi2 = 13.31, p = 0.04), duration of fistula (chi2 = 19.6, p =
      0.03), surgeons' experience (chi2 = 7.11, p = 0.04), and place of previous
      attempt at repair (chi2 = 6.35, p = 0.02). There were no complications in 86.4%.
      CONCLUSIONS: The success rate was good. Patients who had previous failed repairs
      at the fistula centre had better outcomes after the repeat surgeries.
      Centralizing fistula care will enhance optimal outcomes. It may also boost
      training and research in this specialty.

PMID- 30097668
TI  - Flexor carpi radialis brevis: a rare accessory muscle presenting as an
      intersection syndrome of the wrist.
AB  - The flexor carpi radialis brevis (FCRB) is a rare accessory muscle of the forearm
      and wrist. It is typically asymptomatic, but has been discovered either
      incidentally during cadaveric studies or at the time of surgery in patients with
      distal forearm injury. Rarely, the FCRB muscle is associated with pain. We report
      a patient with wrist pain related to intersection between the tendon of the FCRB
      muscle and the tendon of the flexor carpi radialis (FCR) muscle, with an
      associated longitudinal split tear of the FCR tendon, documented by magnetic
      resonance imaging (MRI). To our knowledge, this is only the second report in the
      English literature of this intersection syndrome.

PMID- 30097670
TI  - Influence of lanreotide on uptake of 68Ga-DOTATATE in patients with
      neuroendocrine tumours: a prospective intra-patient evaluation.
AB  - INTRODUCTION: Somatostatin receptor imaging with PET is the standard of care for
      patients with a neuroendocrine tumour (NET). Since therapy and imaging with
      somatostatin analogues utilize the same receptor, current guidelines recommend
      withdrawing long-acting somatostatin analogues for 3-4 weeks prior to
      somatostatin receptor PET imaging. The aim of this study is to prospectively
      assess the effect of lanreotide use on the uptake of 68Ga-DOTATATE intra
      individually 1 day prior to and 1 day post injection of lanreotide. METHODS:
      Thirty-four patients with metastatic and/or unresectable NET and currently on
      lanreotide therapy for at least 4 months were included in the study. A 68Ga
      DOTATATE PET/CT scan was performed on the day before and the day after lanreotide
      injection. In each patient 68Ga-DOTATATE uptake (SUVmax, mean, peak) was assessed
      in both tumour lesions and normal tissue. All scans were assessed by two blinded
      nuclear medicine physicians for visual analysis. Paired T-tests were performed to
      determine the differences between the scans. RESULTS: Of the 34 patients
      included, 31 were available for analyses in which 190 tumour lesions were
      measured. Uptake of 68Ga-DOTATATE in tumour lesions was increased significantly
      after lanreotide, but decreased significantly in the liver, spleen, and thyroid
      gland resulting in a higher tumour-to-liver ratio. CONCLUSION: Lanreotide
      injection prior to 68Ga-DOTATATE PET/CT does not result in decreased tumour
      uptake. In contrast, tumour uptake was increased, whereas the uptake in normal
      organs is decreased, leading to an increased tumour-to-liver ratio. However,
      these differences were small and not deemed clinically relevant. These results
      strongly suggest that discontinuation of lanreotide injections in the weeks prior
      to 68Ga-DOTATATE PET examinations is unnecessary and does not compromise nuclear
      medicine imaging results.

PMID- 30097671
TI  - The Application of the Acellular Dermal Matrix in the Correction of the Tear
      Trough Deformity.
AB  - OBJECTIVE: The acellular dermal matrix (ADM) used in correcting the tear trough
      deformity has been reported, but there were only a few cases. The long-term
      effectiveness of ADM was not clear. We aim to discuss the technique and the
      effect of using ADM to correct the tear trough deformity through more cases.
      METHODS: A retrospective study was conducted from January 2012 to January 2017.
      Twenty-six patients who showed obvious tear trough deformity with moderate or
      severe orbital fat bulging and excess of lower eyelid skin were treated with ADM
      to improve the appearance of the midface. Follow-up was performed for 2-12 months
      in 26 cases. The level of postoperative satisfaction was assessed by interview
      during the follow-up and rated as very satisfied, satisfied, acceptable, or
      unacceptable. RESULT: Twenty patients were very satisfied for having achieved
      complete correction. Three patients were satisfied for having achieved obvious
      improvement. Three patients felt the results were just acceptable and were
      refilled because of the insufficiency of the filler. No one was unacceptable.
      There were no complications such as rapid resorption, rejection, or inflammation.
      CONCLUSION: The method of using ADM for the correction of tear trough deformity
      has the advantages of low absorption rate, good appearance, and high security. It
      provides a new choice for the treatment of tear trough deformity. LEVEL OF
      EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 30097672
TI  - One-Piece Nasal Osteotomy for the Correction of a Centrally Deviated Nose.
AB  - BACKGROUND: A severely crooked nose due to trauma or other causes is difficult to
      correct. Although various nasal osteotomy techniques have been suggested,
      satisfactory outcomes have not always been achieved especially in centrally
      deviated noses. Definite correction of the midline and shape of the bony
      framework is necessary. We aimed to investigate a novel one-piece nasal bone
      osteotomy approach consisting of transverse osteotomy continued with bilateral
      lateral osteotomies for the correction of a centrally deviated nose. METHODS:
      This retrospective chart review included 66 consecutive patients who underwent
      corrective rhinoplasty with nasal bone osteotomy for a deviated nose. Group 1 was
      treated with one-piece osteotomy, and group 2 was treated with conventional
      lateral and/or medial osteotomy. Available preoperative and postoperative three
      dimensional facial bone computed tomography images were used to quantify nasal
      landmarks through three-dimensional reconstruction. Patient satisfaction was
      evaluated using a rhinoplasty outcome evaluation questionnaire. RESULTS:
      Measurements of nasal landmark angles toward the longitudinal facial midline
      plane showed a statistically narrowed postoperative angle in group 1 (subnasale
      landmark: preoperative angle 1.66 +/- 0.29 degrees  [group 1] vs. 0.76 +/- 1.09
      degrees  [group 2]; postoperative angle 0.96 +/- 0.77 degrees  [group 1] vs. 0.31
      +/- 0.29 degrees  [group 2]). The questionnaire scores revealed higher
      satisfaction (3.11 +/- 2.38 vs. 1.157 +/- 1.147) and a higher proportion of 4
      point scores in group 1. CONCLUSIONS: This is the first study to introduce the
      one-piece nasal osteotomy technique for centrally deviated noses. The technique
      consists of transverse osteotomy with bilateral osteotomies in one stage, thus
      the name "one-piece." Considering anatomic variances in Asian rhinoplasty, a
      deviated nose should be effectively corrected to obtain satisfactory outcomes. We
      demonstrated the efficacy and satisfactory outcomes of this new technique. LEVEL
      OF EVIDENCE IV: This journal requires that authors assign a level of evidence to
      each article. For a full description of these Evidence-Based Medicine ratings,
      please refer to the Table of Contents or the online Instructions to Authors
      www.springer.com/00266 .

PMID- 30097673
TI  - Bernese periacetabular osteotomy through a double approach : Simplification of a
      surgical technique.
AB  - OBJECTIVE: Reorientation of the acetabulum to normalize load transfer or avert
      femoroacetabular pincer impingement to prevent osteoarthritis of the hip.
      INDICATIONS: Persisting acetabular dysplasia after closure of growth plates or
      acetabular malrotation. CONTRAINDICATIONS: High dislocation of hip, secondary
      acetabulum, increased misalignment on functional X-ray, high-grade mobility
      restriction. Relative: degenerative changes, advanced age. SURGICAL TECHNIQUE:
      Bernese periacetabular osteotomy through two incisions; all bone cuts are carried
      out under direct vision. The osteotomies are equivalent to the classic Ganz
      method. In a slightly tilted forward lateral decubitus position, a posterior
      incision is applied for the ischium osteotomy and the caudal portion of the
      retroacetabular osteotomy. The pubis and ilium osteotomies are performed in a
      supine position through an anterior approach with subsequent reorientation and
      screw fixation. The rectus femoris is not dissected unless joint exposure is
      required. POSTOPERATIVE MANAGEMENT: Partial weight bearing with 20 kg for the
      first 6 weeks postoperatively, followed by stepwise transition to full loads
      after radiological control. RESULTS: In total, 34 patients (37 hips) were
      followed up for 20.4 +/- 10.3 months. Tonnis osteoarthritis scale levels remained
      constant. The center-edge angle of Wiberg increased from 13.2 +/- 7.5 degrees  to
      26.5 +/- 6.7 degrees , the Tonnis angle (acetabular index) changed from 13.8 +/-
      6.5 degrees  to 3.4 +/- 4.4 degrees . At follow-up, the Merle d'Aubigne and
      Postel score was 16.5 +/- 1.4; the modified Harris hip score 87.6 +/- 13.9 and
      the International hip outcome tool (iHOT)-12 78.2 +/- 20.3 points. The mean
      surgical time was 213 +/- 29 min. Severe complications were not observed.

PMID- 30097675
TI  - Keep moving and stay in a good shape to find your homologous recombination
      partner.
AB  - Genomic DNA is constantly exposed to damage. Among the lesion in DNA, double
      strand breaks (DSB), because they disrupt the two strands of the DNA double
      helix, are the more dangerous. DSB are repaired through two evolutionary
      conserved mechanisms: Non-Homologous End Joining (NHEJ) and Homologous
      Recombination (HR). Whereas NHEJ simply reseals the double helix with no or
      minimal processing, HR necessitates the formation of a 3'ssDNA through the
      processing of DSB ends by the resection machinery and relies on the recognition
      and pairing of this 3'ssDNA tails with an intact homologous sequence. Despite
      years of active research on HR, the manner by which the two homologous sequences
      find each other in the crowded nucleus, and how this modulates HR efficiency,
      only recently emerges. Here, we review recent advances in our understanding of
      the factors limiting the search of a homologous sequence during HR.

PMID- 30097676
TI  - Tensile gallbladder fundus sign.

PMID- 30097677
TI  - Correction to: Increasing the synthesis of bioactive abietane diterpenes in
      Salvia sclarea hairy roots by elicited transcriptional reprogramming.
AB  - Unfortunately, the second author name was wrongly published in the original
      publication. The correct author name should read as follows.

PMID- 30097674
TI  - Oxidative stress-induced miRNAs modulate AKT signaling and promote cellular
      senescence in uterine leiomyoma.
AB  - : Uterine leiomyomas (ULM) grow under high oxidative stress due to a hypoxic
      microenvironment and defects in redox metabolism. AKT is one major pathway
      activated by reactive oxygen species (ROS) that maintains ULM growth and
      survival. We previously reported that AKT inactivated by AKT inhibitors can
      significantly induce cellular senescence in ULM cells. Since some miRNAs are
      induced by AKT inhibitors in an ROS-dependent manner, we proposed that these
      miRNAs may modulate AKT function and cellular senescence in ULM. We therefore
      established ex vivo models of a three-dimensional ULM spheroid culture system to
      study the role of miRNAs in cellular senescence. Four miRNAs, miR-29b, miR-181a,
      miR-182, and miR-200c, were found to induce cellular senescence in primary ULM
      and myometrium spheroid cultures when stably overexpressed. miR-181a and miR-182
      were found to repress AKT3 and CCND2, respectively. Correspondingly, RNAi of AKT3
      or CCND2 also induced cellular senescence and G0/G1 arrest. Thus, miR-181a and
      miR-182 may drive cellular senescence in ULM by repressing AKT3 and CCND2
      activity, respectively. We further demonstrated that senescent ULM cells can be
      effectively removed by BH3 mimetic ABT263, which provides a new therapeutic venue
      for the treatment of ULM. Our findings suggest that miRNAs are potent modulators
      in regulating the ROS-AKT-cell cycle axis in uterine leiomyoma. KEY MESSAGES: A
      subset of oxidative stress-induced miRNAs is involved in AKT signaling in uterine
      leiomyoma. Overexpression of miR-181a and miR-182 resulted in cellular senescence
      in leiomyoma through repression of AKT3 and CCND2, respectively. Silencing of
      AKT3 and CCND2 drives leiomyoma cell into senescence and cycle arrest.
      Application of our newly developed 3D leiomyoma spheroids can provide a quick and
      reliable ex vivo model for cytopathologic and functional analysis. BH3 mimetics
      can effectively reduce the viability of miRNA-mediated senescent cells in
      leiomyoma.

PMID- 30097678
TI  - The perinatal health of immigrant women in France: a nationally representative
      study.
AB  - OBJECTIVES: Despite the healthy migrant effect, immigrants and descendants of
      immigrants face health challenges and socio-economic difficulties. The objective
      of this study is to examine the perinatal health of women of migrant origin.
      METHODS: The nationwide French ELFE (Etude Longitudinale Francaise Depuis
      l'Enfance) birth cohort study recruited approximately 18,000 women. We studied
      pre-pregnancy BMI, gestational diabetes mellitus (GDM), as well as tobacco, and
      alcohol consumption during pregnancy according to migrant status and region of
      origin. RESULTS: Women from North Africa and Turkey had a higher risk of pre
      pregnancy overweight and GDM, while women from Eastern Europe and Asia had a
      lower risk of pre-pregnancy overweight and obesity, but a higher risk of GDM
      compared to non-immigrants. Women from Sub-Saharan Africa had a higher risk of
      being overweight or obese pre-pregnancy. Compared to non-immigrants, immigrants
      but not descendants of immigrants-had lower levels of tobacco smoking, while
      descendants of immigrants were less likely to drink alcohol during pregnancy.
      CONCLUSIONS: Pregnant women of migrant origin have particular health needs and
      should benefit from a medical follow-up which addresses those needs.

PMID- 30097680
TI  - Integrated approaches to tackling health issues-related to agri-food systems.

PMID- 30097679
TI  - Building collaborative capability between law enforcement and civil society
      leaders to prevent urban violence.
AB  - OBJECTIVES: This research paper analyses how applying a Place-Based Leadership
      Development (P-BLD) programme adds value to an ongoing intersectoral Urban
      Violence Prevention Programme (IUVP) in Kenya building trust within
      collaboratives in the intersection between the historically adversarial law
      enforcement and civil society sectors. METHODS: Data on participants' experience
      of the P-BLD programme were systematically collected through detailed pre- and
      post-session questionnaires which included a series of challenging but open
      questions. A framework analysis was undertaken to draw out the common themes.
      RESULTS: By surfacing emotional, relational and structural tensions between law
      enforcement and civil society within the context of IUVP, the P-BLD programme has
      enabled leaders to become more open to and respecting others' perspectives as a
      first step towards a more collaborative mindset. CONCLUSIONS: The P-BLD programme
      is having a positive impact, explicitly addressing the tensions and enabling
      leaders to share their concerns and challenges in working towards violence
      prevention at the intersection between law enforcement and civil society.
      Moreover, this approach is replicable creating new knowledge and sustainable
      mechanisms for violence prevention within urban areas across the world.

PMID- 30097681
TI  - Anterior-posterior cricoid split combined with silastic T-tube stenting for
      subglottic stenosis in children: a single surgeon's experience.
AB  - PURPOSE: Treatment strategies and clinical outcomes of subglottic stenosis (SGS)
      in children are varied due to the degree and range of stenotic lesions. The
      optimal surgical procedure for SGS in children is still under debate. The aim of
      this study was to evaluate the clinical outcomes of our anterior-posterior
      cricoid (APC) split technique combined with long-term T-tube stenting for grade
      II or III SGS in children. METHODS: A retrospective chart review of children with
      SGS between January 2011 and December 2016 was conducted. APC split was performed
      via open procedure under rigid bronchoscopy. After splitting, a silastic T-tube
      was inserted as a stent and removed 6 months postoperatively. RESULTS: Seven
      children underwent APC split during the period. All children had undergone
      previous tracheostomy, and APC split was performed when the children were 3-9
      years old without any intraoperative complications. Median duration of T-tube
      stenting was 11 months, and all children were decannulated successfully. There
      were T-tube-related complications, including two tube-tip granulation that
      required intervention and one accidental T-tube removal. CONCLUSION: APC split is
      a technically simple and reproducible procedure, and it could be employed as an
      optimal procedure for SGS in children.

PMID- 30097682
TI  - Simulated Marine Heat Wave Alters Abundance and Structure of Vibrio Populations
      Associated with the Pacific Oyster Resulting in a Mass Mortality Event.
AB  - Marine heat waves are predicted to become more frequent and intense due to
      anthropogenically induced climate change, which will impact global production of
      seafood. Links between rising seawater temperature and disease have been
      documented for many aquaculture species, including the Pacific oyster Crassostrea
      gigas. The oyster harbours a diverse microbial community that may act as a source
      of opportunistic pathogens during temperature stress. We rapidly raised the
      seawater temperature from 20  degrees C to 25  degrees C resulting in an oyster
      mortality rate of 77.4%. Under the same temperature conditions and with the
      addition of antibiotics, the mortality rate was only 4.3%, strongly indicating a
      role for bacteria in temperature-induced mortality. 16S rRNA amplicon sequencing
      revealed a change in the oyster microbiome when the temperature was increased to
      25  degrees C, with a notable increase in the proportion of Vibrio sequences.
      This pattern was confirmed by qPCR, which revealed heat stress increased the
      abundance of Vibrio harveyi and Vibrio fortis by 324-fold and 10-fold,
      respectively. Our findings indicate that heat stress-induced mortality of C.
      gigas coincides with an increase in the abundance of putative bacterial pathogens
      in the oyster microbiome and highlights the negative consequences of marine heat
      waves on food production from aquaculture.

PMID- 30097683
TI  - Predictors of mortality in ischaemic versus non-ischaemic functional mitral
      regurgitation after successful transcatheter mitral valve repair using MitraClip:
      results from two high-volume centres.
AB  - INTRODUCTION: Transcatheter edge-to-edge mitral valve repair using the MitraClip
      has been widely performed in surgical high-risk patients with reduced left
      ventricular systolic function and severe functional mitral regurgitation (FMR).
      Ischaemic heart disease is the leading aetiology of heart disease worldwide. We
      aimed to assess the clinical implications of ischaemic aetiology in patients with
      severe FMR who underwent MitraClip implantation. METHODS AND RESULTS: From two
      high-volume centres in Germany, we retrospectively compared the clinical outcomes
      and clinical predictors of all-cause mortality after MitraClip implantation in
      patients with ischaemic (I-FMR) and non-ischaemic FMR (NI-FMR). In the overall
      FMR cohort (n = 575), there were 336 (58%) patients with I-FMR and 239 (42%) with
      NI-FMR. There was no significant difference in survival between the two groups
      (log-rank p = 0.78). In a multivariable Cox regression analysis of all-cause
      mortality, different predictors were observed for either group. In I-FMR
      patients, decreasing tricuspid annular systolic excursion [adjusted hazard ratio
      (HRadj) 1.06, 95% confidence interval (95% CI) 1.01-1.14 /1 mm, p = 0.028] and
      increasing logistic EuroSCORE (HRadj 1.02, 95% CI 1.00-1.03, p = 0.037) were
      independent predictors, whereas in NI-FMR patients, NT-pro BNP (HRadj 1.05, 95%
      CI 1.02-1.08, p = 0.001) and age (HRadj 1.06, 95% CI 1.01-1.11, p = 0.013) were
      independently predictive of mortality. CONCLUSIONS: Despite the similar survival
      between ischaemic and non-ischaemic FMR, different predictors of all-cause
      mortality were demonstrated. Further clinical studies are mandated to focus on
      each FMR subgroup with stratification by ischaemic origin.

PMID- 30097684
TI  - Symptom patterns and clinical outcomes in women versus men with systolic heart
      failure and depression.
AB  - BACKGROUND: Depression is more common in females than in males and is 3-5 times
      more prevalent in patients with heart failure (HF) than in the general
      population. The 9-item Patient Health Questionnaire (PHQ-9) is a validated
      depression screening instrument; higher sum-scores predict adverse clinical
      outcomes. Sex- and gender differences in PHQ-9 symptom profile, diagnostic and
      prognostic properties, and impact on health-related quality of life (HRQOL) have
      not been comprehensively studied in HF patients. METHODS AND RESULTS: This post
      hoc analysis from the Interdisciplinary Network Heart Failure program enrolled
      852/1022 participants (67 +/- 13 years, 28% female) who completed the PHQ-9 at
      hospital discharge after cardiac decompensation. All had a left ventricular
      ejection fraction <= 40%. Women had a higher mean PHQ-9 sum-score than men (8.4
      +/- 5.6 vs. 7.4 +/- 5.5; p = 0.027), and higher proportions rated the following
      items >= 2 (i.e., present on >= 50% of days): 'feeling down, hopeless' (25.8 vs.
      18.0%; p = 0.011); 'fatigue' (51.9 vs. 37.2%; p < 0.001); and 'trouble
      concentrating' (21.6 vs. 15.4%; p = 0.032). A PHQ-9 sum-score >= 10 predicted
      increased mortality in women [hazard ratio 1.91 (95% confidence interval 1.06
      3.43); p = 0.030] and men [2.10 (1.43-3.09); p < 0.001] and was associated with
      worse HRQOL (p < 0.001 for all comparisons). Sum-scores >= 10 predicted higher re
      hospitalization rates in men only [1.35 (1.08-1.69); p = 0.008]. CONCLUSIONS:
      Differences in several PHQ-9 items indicated sex- or gender-specific depression
      symptomatology in HF. For both sexes, HRQOL and survival were worse when PHQ-9
      sum-score was >= 10, but higher sum-scores predicted higher re-hospitalization
      rates in men only. Considering these specific aspects might help optimize care
      strategies in HF.

PMID- 30097685
TI  - [The S2k guideline: Indications for knee endoprosthesis : Evidence and consent
      based indications for total knee arthroplasty].
AB  - Total knee arthroplasty (TKA) is one of the most frequent surgical procedures in
      orthopaedic surgery. Until now there have not been any standardized indication
      criteria, which might contribute to the large geographical differences in the
      frequency of TKA. This guideline aims to consent minimal requirements (main
      criteria), additional important aspects (minor criteria), as well as relative and
      absolute contraindications for TKA. The following main criteria have been
      consented: knee pain, radiological confirmation of osteoarthritis or
      osteonecrosis, inadequate response to conservative treatment, adverse impact of
      knee disease on the patient's quality of life and the burden of suffering due to
      the knee disease. Relative contraindications have been consented as severe
      general disease with reduced life expectancy and a BMI >=40; absolute
      contraindications are an active infection and if the patient is not able to
      undergo major surgery.

PMID- 30097686
TI  - [Conservative treatment of atraumatic femoral head necrosis].
AB  - BACKGROUND: Femoral head necrosis is a progressive disease that can progress
      within a relatively short time. Therefore, an early and clear diagnosis including
      stage classification and treatment is necessary to prevent or delay the onset of
      the femoral head and joint destruction. TREATMENT: In addition to the
      identification of possible risk factors and treatment, the question of the
      available treatment options arises. The present article deals with conservative
      treatment options and presents the published results in the sense of the
      currently available evidence and against the background of the S3 guideline on
      atraumatic femoral head necrosis. The results of physical therapy, drug therapy
      (iloprost and bisphosphonates ), electrotherapy, shockwave therapy, etc. are
      presented. In the early stages of femoral head necrosis with low expansion,
      alendronate gives positive results. Iloprost is also a successful conservative
      treatment option in the early stages of atraumatic femoral head necrosis (ARCO I
      and II). In stages ARCO III and IV, Ilomedin is no longer indicated.
      Anticoagulants, such as enoxaparin, have demonstrated an arthroprotective effect.

PMID- 30097687
TI  - Predicting meniscal tear stability across knee-joint flexion using finite-element
      analysis.
AB  - PURPOSE: To analyse the stress distribution through longitudinal and radial
      meniscal tears in three tear locations in weight-bearing conditions and use it to
      ascertain the impact of tear location and type on the potential for healing of
      meniscal tears. METHODS: Subject-specific finite-element models of a healthy knee
      under static loading at 0 degrees , 20 degrees , and 30 degrees  knee flexion
      were developed from unloaded magnetic resonance images and weight-bearing,
      contrast-enhanced computed tomography images. Simulations were then run after
      introducing tears into the anterior, posterior, and midsections of the menisci.
      RESULTS: Absolute differences between the displacements of anterior and posterior
      segments modelled in the intact state and those quantified from in vivo weight
      bearing images were less than 0.5 mm. There were tear-location-dependent
      differences between hoop stress distributions along the inner and outer surfaces
      of longitudinal tears; the longitudinal tear surfaces were compressed together to
      the greatest degree in the lateral meniscus and were most consistently in
      compression on the midsections of both menisci. Radial tears resulted in an
      increase in stress at the tear apex and in a consistent small compression of the
      tear surfaces throughout the flexion range when in the posterior segment of the
      lateral meniscus. CONCLUSIONS: Both the type of meniscal tear and its location
      within the meniscus influenced the stresses on the tear surfaces under weight
      bearing. Results agree with clinical observations and suggest reasons for the
      inverse correlation between longitudinal tear length and healing, the inferior
      healing ability of medial compared with lateral menisci, and the superior healing
      ability of radial tears in the posterior segment of the lateral meniscus compared
      with other radial tears. This study has shown that meniscal tear location in
      addition to type likely plays a crucial role in dictating the success of non
      operative treatment of the menisci. This may be used in decision making regarding
      conservative or surgical management.

PMID- 30097688
TI  - The absorbable subacromial spacer for irreparable posterosuperior cuff tears has
      inconsistent results.
AB  - PURPOSE: To evaluate the 2-year results of an absorbable subacromial spacer in
      patients with irreparable posterosuperior rotator cuff tears. METHODS:
      Prospective longitudinal study of a consecutive case series of 16 subjects with
      irreparable tears of the posterosuperior rotator cuff in which the InSpace(r)
      subacromial spacer was arthroscopically implanted. A full clinical evaluation
      that included the Constant test, Simple Shoulder Test (SST) and the QuickDash
      questionnaire was performed preoperatively and at 12 and 24 months follow-up. The
      primary outcome for assessing the success of the procedure was a variable
      composed of a clinically relevant variation of the Constant (established in an
      improvement greater than 10 points) and the absence of surgical reintervention.
      RESULTS: Fifteen subjects (11 women/4 men, median age = 69.4 years [interquartile
      range 7.50], range 60-80 years) completed the 2-year of follow-up. According to
      the main evaluation criteria, only 6 patients (40%) had a successful outcome.
      Five subjects required reconversion to a reverse shoulder arthroplasty (at a
      median of 9.8 months postoperatively) due to absence of clinical improvement or
      worsening of symptoms. Of the ten remaining subjects, only 6 had improvements
      greater than 10 points in the Constant score. Despite of this, these 10 subjects
      had, on average, some improvement in the Constant test (preoperative Constant:
      median 35.0 [27.0-52.5] vs Constant at 24 months: 53.5 [55.0-84.0], significant
      differences p = 0.02), in the SST (3.0 [2.0-4.0] vs 6.0 [3.25-7.75], p = 0.039)
      and in the QuickDASH test (37.0 [33.25-40.0] vs 27.5 [20.5-32.75], p = 0.012).
      CONCLUSIONS: The outcomes of the implantation of the subacromial biodegradable
      spacer at 2-year follow-up are not satisfactory. In this small case series only
      40% of patients seem to clearly benefit from surgery. One in three required
      revision to a reverse shoulder arthroplasty. The described technique does not
      seem a reasonable alternative for the management of the majority of patients with
      irreparable ruptures of the rotator cuff. The indications of this device should
      be more clearly defined. LEVEL OF EVIDENCE: IV.

PMID- 30097689
TI  - Low prevalence of relevant associated articular lesions in patients with acute
      III-VI acromioclavicular joint injuries.
AB  - PURPOSE: To define the prevalence of associated articular injuries in patients
      with severe (Rockwood's III-VI) acute acromioclavicular joint injuries and to
      find out how many of these were associated with the traumatic event and required
      surgical treatment. METHODS: Retrospective observational multicentric study
      performed in ten centres included patients who required surgery for acute
      acromioclavicular joint injuries between 2010 and 2017. The inclusion criteria
      were: presence of an acute acromioclavicular joint injury (grades III-IV-V-VI)
      and surgical treatment within 3 weeks of injury that included a full arthroscopic
      evaluation of the shoulder. Basic epidemiological data, severity of the original
      injury, prelesional sport level and prelesional work site requirements were
      recorded. The presence of intraarticular glenohumeral lesions and information of
      their characteristics, treatment, and whether each lesion was considered acute or
      pre-existing was also recorded. RESULTS: Two-hundred one subjects [mean (SD) age
      36.7 (11.7) years] with acute acromioclavicular joint injuries (110 Rockwood type
      III, 34 type IV, 56 type V and 1 type VI) fulfilled the inclusion criteria. A
      total of 28 (13.9%) associated articular lesions were found. These lesions were
      more often found in grade IV injuries (26.5% in grade IV vs 11.4% in grade III, p
      = 0.037) and presented in males (18.7% in males vs 4% in females, p = 0.015).
      Age, laterality, sport level or work requirements did not affect the prevalence
      of associated lesions. Twelve were rotator cuff tears (6 PASTA lesions, 3 partial
      supscapularis tears, 2 bursal supraspinatus tears and 1 full-thickness
      supraspinatus tear), 16 were labral tears (9 anterior, 1 posteroinferior and 6
      SLAP). Only 14 (50% of lesions, 7% of total subjects) were considered acute and
      all but one (an SLAP type 2 tear) required further surgical attention. Most pre
      existing lesions were left untreated (n = 7) or managed with minimal debridement
      (n = 6), and only two required further surgery. The prevalence of associated
      lesions that required surgical management was 7.46%. CONCLUSIONS: The prevalence
      of relevant associated lesions in subjects with acute grade III to VI ACJI is
      relatively low. Only 14% of subjects have an associated lesion and only half of
      these required further surgical attention. LEVEL OF EVIDENCE: Retrospective case
      series, level IV.

PMID- 30097690
TI  - Significant anterior enlargement of femoral tunnel aperture after hamstring ACL
      reconstruction, compared to bone-patellar tendon-bone graft.
AB  - PURPOSE: This study aimed to retrospectively compare the enlargement and
      migration of the femoral tunnel aperture after anatomic rectangular tunnel
      anterior cruciate ligament (ACL) reconstruction with a bone-patella tendon-bone
      (BTB) or hamstring tendon (HT) graft using three-dimensional (3-D) computer
      models. METHODS: Thirty-two patients who underwent ACL reconstruction and
      postoperative computed tomography (CT) at 3 weeks and 6 months were included in
      this study. Of these, 20 patients underwent ACL reconstruction with a BTB graft
      (BTBR group), and the remaining 12 with an HT graft (HTR group). The area of the
      femoral tunnel aperture was extracted and measured using a 3-D computer model
      generated from CT images. Changes in the area and migration direction of the
      femoral tunnel aperture during this period were compared between the two groups.
      RESULTS: In the HTR group, the area of the femoral tunnel aperture was
      significantly increased at 6 months compared to 3 weeks postoperatively (P <
      0.05). The average area of the femoral tunnel aperture at 6 months
      postoperatively was larger by 16.0 +/- 12.4% in the BTBR group and 41.9 +/- 22.2%
      in the HTR group, relative to that measured at 3 weeks postoperatively (P <
      0.05). The femoral tunnel aperture migrated in the anteroinferior direction in
      the HTR group, and only in the inferior direction in the BTBR group. CONCLUSIONS:
      The femoral tunnel aperture in the HTR group was significantly more enlarged and
      more anteriorly located at 6 months after ACL reconstruction, compared to the
      BTBR group. LEVEL OF EVIDENCE: IV.

PMID- 30097691
TI  - Celiac disease biomarkers identified by transcriptome analysis of small
      intestinal biopsies.
AB  - Establishing a celiac disease (CD) diagnosis can be difficult, such as when CD
      specific antibody levels are just above cutoff or when small intestinal biopsies
      show low-grade injuries. To investigate the biological pathways involved in CD
      and select potential biomarkers to aid in CD diagnosis, RNA sequencing of
      duodenal biopsies from subjects with either confirmed Active CD (n = 20) or
      without any signs of CD (n = 20) was performed. Gene enrichment and pathway
      analysis highlighted contexts, such as immune response, microbial infection,
      phagocytosis, intestinal barrier function, metabolism, and transportation. Twenty
      nine potential CD biomarkers were selected based on differential expression and
      biological context. The biomarkers were validated by real-time polymerase chain
      reaction of eight RNA sequencing study subjects, and further investigated using
      an independent study group (n = 43) consisting of subjects not affected by CD,
      with a clear diagnosis of CD on either a gluten-containing or a gluten-free diet,
      or with low-grade intestinal injury. Selected biomarkers were able to classify
      subjects with clear CD/non-CD status, and a subset of the biomarkers (CXCL10,
      GBP5, IFI27, IFNG, and UBD) showed differential expression in biopsies from
      subjects with no or low-grade intestinal injury that received a CD diagnosis
      based on biopsies taken at a later time point. A large number of pathways are
      involved in CD pathogenesis, and gene expression is affected in CD mucosa already
      in low-grade intestinal injuries. RNA sequencing of low-grade intestinal injuries
      might discover pathways and biomarkers involved in early stages of CD
      pathogenesis.

PMID- 30097692
TI  - The functional role of sodium taurocholate cotransporting polypeptide NTCP in the
      life cycle of hepatitis B, C and D viruses.
AB  - Chronic hepatitis B, C and D virus (HBV, HCV and HDV) infections are a major
      cause of liver disease and cancer worldwide. Despite employing distinct
      replication strategies, the three viruses are exclusively hepatotropic, and
      therefore depend on hepatocyte-specific host factors. The sodium taurocholate co
      transporting polypeptide (NTCP), a transmembrane protein highly expressed in
      human hepatocytes that mediates the transport of bile acids, plays a key role in
      HBV and HDV entry into hepatocytes. Recently, NTCP has been shown to modulate HCV
      infection of hepatocytes by regulating innate antiviral immune responses in the
      liver. Here, we review the current knowledge of the functional role and the
      molecular and cellular biology of NTCP in the life cycle of the three major
      hepatotropic viruses, highlight the impact of NTCP as an antiviral target and
      discuss future avenues of research.

PMID- 30097693
TI  - Neuroimaging of central diabetes insipidus-when, how and findings.
AB  - Central or neurogenic diabetes insipidus (CDI) is due to deficient synthesis or
      secretion of antidiuretic hormone (ADH), also known as arginine vasopressin
      peptide (AVP). It is clinically characterised by polydipsia and polyuria (urine
      output > 30 mL/kg/day) of dilute urine (< 250 mOsm/L). It is the result of a
      defect in one of more sites involving the hypothalamic osmoreceptors, supraoptic
      or paraventricular nuclei of the hypothalamus, median eminence of the
      hypothalamus, infundibulum or the posterior pituitary gland. A focused MRI
      pituitary gland or sella protocol is essential. There are several neuroimaging
      correlates and causes of CDI, illustrated in this review. The most common causes
      are benign or malignant neoplasms of the hypothalamic-pituitary axis (25%),
      surgery (20%), head trauma (16%) or familial causes (10%). No cause is identified
      in up to 30% of cases. Knowledge of the anatomy and physiology of the hypothalamo
      neurohypophyseal axis is crucial when evaluating a patient with CDI. Establishing
      the aetiology of CDI with MRI in combination with clinical and biochemical
      assessment facilitates appropriate targeted treatment. The aim of the pictorial
      review is to illustrate the wide variety of causes of CDI on neuroimaging,
      highlight the optimal MRI protocol and to revise the detailed neuroanatomy and
      neurophysiology required to interpret these studies.

PMID- 30097694
TI  - Anti-angiogenic effects of the DPP-4 inhibitor linagliptin via inhibition of
      VEGFR signalling in the mouse model of oxygen-induced retinopathy.
AB  - AIMS/HYPOTHESIS: Linagliptin has protective effects on the retinal neurovascular
      unit but, in proliferative retinopathy, dipeptidyl peptidase 4 (DPP-4) inhibition
      could be detrimental. The aim of this study was to assess the effect of
      linagliptin on ischaemia-induced neovascularisation of the retina. METHODS:
      C57BL/6J and glucagon-like peptide 1 (GLP-1) receptor (Glp1r)-/- mice were
      subjected to a model of oxygen-induced retinopathy (OIR). Both strains were
      subcutaneously treated with linagliptin from postnatal days 12 to 16. Non
      injected OIR and non-exposed mice served as controls. Capillary proliferations
      and systemic levels of active GLP-1 were quantified. The effects of linagliptin
      on vascular endothelial growth factor (VEGF)-induced downstream signalling were
      assessed in human umbilical vein endothelial cells (HUVECs) using western blot
      for retinal phosphorylated extracellular signal-regulated kinase (ERK)1/2 and
      retinal gene expression analyses. RESULTS: Linagliptin treatment led to an
      increase in active GLP-1 and a decreased number of neovascular nuclei in OIR mice
      vs controls (-30%, p < 0.05). As the reduction in neovascularisation was similar
      in both C57BL/6J and Glp1r-/- mice, the anti-angiogenic effects of linagliptin
      were independent of GLP-1R status. The expression of Vegf (also known as Vegfa)
      and Hif1a was increased in C57BL/6J OIR mice upon linagliptin treatment (three-
      vs 1.5-fold, p < 0.05, p < 0.01, respectively). In HUVECs, linagliptin inhibited
      VEGF-induced increases in mitogen-activated protein kinase (MAPK)/ERK (-67%, p <
      0.001) and MAPK/c-Jun N-terminal kinase (JNK) (-13%, p < 0.05) pathway
      activities. In the retinas of C57BL/6J mice, p-ERK1/2 levels were significantly
      reduced upon linagliptin treatment (-47%, p < 0.05). CONCLUSIONS/INTERPRETATION:
      Systemic treatment with linagliptin demonstrated GLP-1R-independent anti
      angiogenic effects mediated by an inhibition of VEGF receptor downstream
      signalling. The specific effects of linagliptin on diabetic retinopathy are of
      potential benefit for individuals with diabetes, independent of metabolic
      effects.

PMID- 30097695
TI  - Characterization of oil-producing yeast Lipomyces starkeyi on glycerol carbon
      source based on metabolomics and 13C-labeling.
AB  - Lipomyces starkeyi is an oil-producing yeast that can produce triacylglycerol
      (TAG) from glycerol as a carbon source. The TAG was mainly produced after
      nitrogen depletion alongside reduced cell proliferation. To obtain clues for
      enhancing the TAG production, cell metabolism during the TAG-producing phase was
      characterized by metabolomics with 13C labeling. The turnover analysis showed
      that the time constants of intermediates from glycerol to pyruvate (Pyr) were
      large, whereas those of tricarboxylic acid (TCA) cycle intermediates were much
      smaller than that of Pyr. Surprisingly, the time constants of intermediates in
      gluconeogenesis and the pentose phosphate (PP) pathway were large, suggesting
      that a large amount of the uptaken glycerol was metabolized via the PP pathway.
      To synthesize fatty acids that make up TAG from acetyl-CoA (AcCoA), 14 molecules
      of nicotinamide adenine dinucleotide phosphate (NADPH) per C16 fatty acid
      molecule are required. Because the oxidative PP pathway generates NADPH, this
      pathway would contribute to supply NADPH for fatty acid synthesis. To confirm
      that the oxidative PP pathway can supply the NADPH required for TAG production,
      flux analysis was conducted based on the measured specific rates and mass
      balances. Flux analysis revealed that the NADPH necessary for TAG production was
      supplied by metabolizing 48.2% of the uptaken glycerol through gluconeogenesis
      and the PP pathway. This result was consistent with the result of the 13C
      labeling experiment. Furthermore, comparison of the actual flux distribution with
      the ideal flux distribution for TAG production suggested that it is necessary to
      flow more dihydroxyacetonephosphate (DHAP) through gluconeogenesis to improve TAG
      yield.

PMID- 30097698
TI  - Subtherapeutic doses of SSRI antidepressants demonstrate considerable serotonin
      transporter occupancy: implications for tapering SSRIs.

PMID- 30097697
TI  - The Response of Neotropical Fish Species (Brazil) on the Water Pollution: Metal
      Bioaccumulation and Genotoxicity.
AB  - The streams and rivers of the Upper Parana River Basin have been seriously
      affected by impacts of high population density around the basin area. Fishes are
      widely used as models to assess the health of aquatic ecosystems, being
      considered as bioindicators of environmental pollution. In this context, our
      objective was to assess the potential genotoxic and mutagenic effects of the
      polluted water in three native fish species (Astyanax lacustris, Hypostomus
      ancistroides, and Rhamdia quelen) from Taruma Microbasin, Upper Parana River,
      Brazil. We also investigated the concentration of metals in water and in fish
      muscle to verify bioavailability and bioaccumulation of metals. For both less
      impacted sites (LI) and impacted sites (IMP) of the microbasin, the
      concentrations of metals were above the maximum limit allowed by Brazilian
      legislation (Resolution CONAMA 357/2005), except for Pb, total Cr, and Cu at LI
      sites and total Cr at IMP sites. A. lacustris showed a higher frequency of
      micronuclei (MN) at IMP sites compared with LI sites (p < 0.0001). We found no
      significant differences in MN frequency between site classes for H. ancistroides
      and R. quelen (p > 0.05). There were no significant differences between site
      classes regarding to nuclear abnormalities in erythrocytes frequencies (p >
      0.05). A. lacustris from IMP sites had higher concentrations of Pb, Cu, Fe, Zn,
      and Ni in muscle tissue (p < 0.05), whereas H. ancistroides from IMP sites had
      higher concentration of Cr, Cu, and Ni (p < 0.0001) and R. quelen showed higher
      concentration of Cd, Fe, and Ni at these sites (p < 0.0001). So, the chosen
      biomarkers are able to identify the environmental risk of the water pollution.

PMID- 30097699
TI  - Recent biomonitoring reports on phosphate ester flame retardants: a short review.
AB  - Organophosphate triesters (PEFRs) are used increasingly as flame retardants and
      plasticizers in a variety of applications, such as building materials, textiles,
      and electric and electronic equipment. They have been proposed as alternatives to
      brominated flame retardants. This updated review shows that biomonitoring has
      gained incrementally greater importance in evaluating human exposure to PEFRs,
      and it holds the advantage of taking into account the multiple potential sources
      and various intake pathways of PEFRs. Simultaneous and extensive internal
      exposure to a broad range of PEFRs have been reported worldwide. Their
      metabolites, mainly dialkyl or diaryl diesters, have been used as biomarkers of
      exposure and have been ubiquitously detected in the urine of adults and children
      in the general population. Concentrations and profiles of PEFR urinary
      metabolites are seen to be variable and are highly dependent on individual and
      environmental factors, including age, country regulation of flame retardants, and
      types and quantities of emissions in microenvironments, as well as analytical
      procedures. Additional large biomonitoring studies, using a broad range of
      urinary diesters and hydroxylated metabolites, would be useful to improve the
      validity of the biomarkers and to refine assessments of human exposure to PEFRs.

PMID- 30097700
TI  - Chemical-induced contact allergy: from mechanistic understanding to risk
      prevention.
AB  - Chemical allergens are small molecules able to form a sensitizing complex once
      they bound to proteins. One of the most frequent manifestations of chemical
      allergy is contact hypersensitivity, which can have serious impact on quality of
      life. Allergic contact dermatitis is a predominantly CD8 + T cell-mediated immune
      disease, resulting in erythema and eczema. Chemical allergy is of considerable
      importance to the toxicologist, who has the responsibility of identifying and
      characterizing the allergenic potential of chemicals, and estimating the risk
      they pose to human health. This review aimed at exploring the phenomena of
      chemical-induced contact allergy starting from a mechanistic understanding,
      immunoregulatory mechanisms, passing through the potency of contract allergen
      until the hazard identification, pointing out the in vitro models for assessing
      contact allergen-induced cell activation and the risk prevention.

PMID- 30097696
TI  - Targeting pericytes for therapeutic approaches to neurological disorders.
AB  - Many central nervous system diseases currently lack effective treatment and are
      often associated with defects in microvascular function, including a failure to
      match the energy supplied by the blood to the energy used on neuronal
      computation, or a breakdown of the blood-brain barrier. Pericytes, an under
      studied cell type located on capillaries, are of crucial importance in regulating
      diverse microvascular functions, such as angiogenesis, the blood-brain barrier,
      capillary blood flow and the movement of immune cells into the brain. They also
      form part of the "glial" scar isolating damaged parts of the CNS, and may have
      stem cell-like properties. Recent studies have suggested that pericytes play a
      crucial role in neurological diseases, and are thus a therapeutic target in
      disorders as diverse as stroke, traumatic brain injury, migraine, epilepsy,
      spinal cord injury, diabetes, Huntington's disease, Alzheimer's disease,
      diabetes, multiple sclerosis, glioma, radiation necrosis and amyotrophic lateral
      sclerosis. Here we report recent advances in our understanding of pericyte
      biology and discuss how pericytes could be targeted to develop novel therapeutic
      approaches to neurological disorders, by increasing blood flow, preserving blood
      brain barrier function, regulating immune cell entry to the CNS, and modulating
      formation of blood vessels in, and the glial scar around, damaged regions.

PMID- 30097701
TI  - MicroRNA-942 mediates hepatic stellate cell activation by regulating BAMBI
      expression in human liver fibrosis.
AB  - MicroRNA (miRNA)-mediated gene regulation contributes to liver pathophysiology,
      including hepatic stellate cell (HSC) activation and fibrosis progression. Here,
      we investigated the role of miR-942 in human liver fibrosis. The expression of
      miR-942, HSC activation markers, transforming growth factor-beta pseudoreceptor
      BMP and activin membrane-bound inhibitor (BAMBI), as well as collagen deposition,
      were investigated in 100 liver specimens from patients with varying degree of
      hepatitis B virus (HBV)-related fibrosis. Human primary HSCs and the immortalized
      cell line (LX2 cells) were used for functional studies. We found that miR-942
      expression was upregulated in activated HSCs and correlated inversely with BAMBI
      expression in liver fibrosis progression. Transforming growth factor beta (TGF
      beta) and lipopolyssacharide (LPS), two major drivers of liver fibrosis and
      inflammation, induce miR-942 expression in HSCs via Smad2/3 respective NF
      kappaB/p50 binding to the miR-942 promoter. Mechanistically, the induced miR-942
      degrades BAMBI mRNA in HSCs, thereby sensitizing the cells for fibrogenic TGF
      beta signaling and also partly mediates LPS-induced proinflammatory HSC fate. In
      conclusion, the TGF-beta and LPS-induced miR-942 mediates HSC activation through
      downregulation of BAMBI in human liver fibrosis. Our study provides new insights
      on the molecular mechanism of HSC activation and fibrosis.

PMID- 30097702
TI  - Effect of acute exposure to toluene on cortical excitability, neuroplasticity,
      and motor learning in healthy humans.
AB  - Toluene is a well-known neurotoxic organic solvent and a major component of many
      industrial and commercial products such as adhesives, paint thinners and
      gasoline. Many workers are regularly exposed to toluene in their working
      environment and occupational exposure limits (OELs) have been set to avoid
      adverse health effects. These OELs or short-term exposure limits vary from 14 to
      300 ppm across countries partly due to heterogeneity of the findings from animal
      and human studies about its neurotoxic effects and the evaluation of the
      adversity of the underlying mechanisms. Furthermore, its acute neurophysiological
      effects remain poorly understood in humans. The purpose of this study was to
      investigate the effects of acute exposure to toluene on cortical excitability,
      plasticity, and implicit motor learning in healthy volunteers. Seventeen subjects
      were assessed with different transcranial magnetic stimulation measurements:
      motor thresholds, short-latency intracortical inhibition and intracortical
      facilitation, and short-interval afferent inhibition before and after clean air
      or toluene (single peak of 200 ppm) administration. Furthermore, we evaluated
      long-term potentiation-like neuroplasticity induced by anodal transcranial direct
      current stimulation (tDCS) over the motor cortex, and the participants conducted
      a motor sequence learning task, the serial reaction time task. Our findings
      revealed that toluene abolished the plasticity induced by anodal tDCS, attenuated
      intracortical facilitation, and increased inhibition in the short-latency
      afferent inhibition measure, while cortico-spinal excitability and intracortical
      inhibition were not affected. On the behavioural level, toluene did not alter
      performance of the motor learning task. These results suggest that toluene might
      act by modulating NMDA receptor activity, as well as cortical glutamatergic and
      cholinergic neurotransmission in the human brain. This study encourages further
      research to obtain more knowledge about mechanisms of action and effects of
      toluene on both naive and chronically exposed populations.

PMID- 30097703
TI  - [Osteomalacia-Clinical aspects, diagnostics and treatment].
AB  - Osteomalacia is a bone disease caused by impaired skeletal mineralization.
      Vitamin D dependent types have to be distinguished from hypophosphatemic forms.
      Typical signs and symptoms include diffuse bone pain, muscle weakness and
      fragility fractures. The fracture pattern in osteomalacia is typically different
      from that of osteoporosis. Fragility fractures of the pelvis, sacrum, distal
      parts of the foot, proximal tibia and ribs are indicators for osteomalacia,
      whereas femoral neck and vertebral fractures (wedged vertebra, fish vertebra,
      vertebra plana and cover plate impression fractures) are typical for
      osteoporosis. Unspecific clinical features may be the reason for a delayed
      diagnosis. The correct classification of the complaint is dependent on the
      knowledge of the pathophysiology of osteomalacia and performance of additional
      bone-specific examinations. Determination of specific laboratory parameters
      should follow a rational algorithm, supplemented by imaging methods and a bone
      biopsy.

PMID- 30097705
TI  - Prognostic Significance of Acute Kidney Injury Following Emergency Laparotomy: A
      Prospective Observational Cohort Study.
AB  - AIMS: Post-operative acute kidney injury (AKI) is a common and independent
      mortality risk factor carrying high clinical and economic cost. This study aimed
      to establish the incidence of AKI in patients undergoing emergency laparotomy
      (EL), to determine patients' risk profile and consequent mortality. METHODS:
      Consecutive 239 patients of median age 68 (IQR 51-76) years, undergoing EL in a
      UK tertiary hospital, were studied. Primary outcome measure was AKI and in
      hospital operative mortality. RESULTS: Ninety-five patients (39.7%) developed
      AKI, which was associated with in-hospital mortality in 32 patients (33.7%)
      compared with 7 patients (4.9%) without AKI. AKI occurred in 81.1% of all
      mortalities, but none occurred when AKI resolved within 48 h of EL. AKI was
      associated with chronic kidney disease, age, serum lactate, white cell count, pre
      EL systolic blood pressure and tachycardia (p < 0.010). Median length of hospital
      stay in AKI survivors was 15 days compared with 11 days in the absence of AKI (p
      < 0.001). On multivariable analysis, only AKI at 48 h post-EL was significantly
      and independently associated with mortality [HR 10.895, 95% CI 3.152-37.659, p <
      0.001]. CONCLUSION: Peri-operative AKI after EL was common and associated with a
      more than sixfold significant greater mortality. Pre-operative risk profile
      assessment and prompt protocol-driven intervention should minimise AKI and reduce
      EL mortality.

PMID- 30097704
TI  - Implementation of Current ENETS Guidelines for Surgery of Small (<=2 cm)
      Pancreatic Neuroendocrine Neoplasms in the German Surgical Community: An Analysis
      of the Prospective DGAV StuDoQ|Pancreas Registry.
AB  - BACKGROUND: ENETS guidelines recommend parenchyma-sparing procedures without
      formal lymphadenectomy, ideally with a minimally invasive laparoscopic approach
      for sporadic small pNENs (<=2 cm). Non-functioning (NF) small pNENs can also be
      observed. The aim of the study was to evaluate how these recommendations are
      implemented in the German surgical community. METHODS: Data from the prospective
      StuDoQ|Pancreas registry of the German Society of General and Visceral Surgery
      were analyzed regarding patient's demographics, tumor characteristics, surgical
      procedures, histology and perioperative outcomes. RESULTS: Eighty-four (29.2%) of
      287 patients had sporadic pNENs <=2 cm. Forty-three (51.2%) patients were male,
      and the mean age at diagnosis was 58.8 +/- 15.6 years. Twenty-five (29.8%) pNENs
      were located in the pancreatic head. The diagnosis pNEN was preoperatively
      established in 53 (65%) of 84 patients. Sixty-two (73.8%) patients had formal
      pancreatic resections, including partial pancreaticoduodenectomy or total
      pancreatectomy (21.4%). Only 22 (26.2%) patients underwent parenchyma-sparing
      resections and 23 (27.4%) patients had minimally invasive procedures. A
      lymphadenectomy was performed in 63 (75.4%) patients, and lymph node metastases
      were diagnosed in 6 (7.2%) patients. Eighty-two (97.7%) patients had an R0
      resection. Sixty (72%) tumors were classified G1, 24 (28%) tumors G2. Twenty
      seven (32.2%) of 84 patients had postoperative relevant Clavien-Dindo grade >=3
      complications. Thirty- and 90-day mortalities were 2.4% and 3.6%. CONCLUSIONS:
      ENETS guidelines for surgery of small pNENs are yet not well accepted in the
      German surgical community, since the rate of formal resections with standard
      lymphadenectomy is high and the minimally invasive approach is underused. The
      attitude to operate small NF tumors seems to be rather aggressive.

PMID- 30097707
TI  - Trends in Retention and Decay of Basic Surgical Skills: Evidence from Addis Ababa
      University, Ethiopia: A Prospective Case-Control Cohort Study.
AB  - INTRODUCTION: While prior studies have evaluated surgical skills simulation and
      retention in highly resourced environments, there is paucity of data on the
      retention of surgical skills taught in simulation laboratory to undergraduate
      students, and virtually none from low-resource settings. We aimed to evaluate the
      trends in retention/decay of surgical skills among medical students in Ethiopia
      and determine whether regular intervention in the form of intermittent skills
      testing can aid retention. METHODS: Forty-four final year medical students were
      randomly divided into two cohorts of 22 students each. All 44 were trained in
      surgical instrument identification, simple interrupted suturing and one-handed
      knot tying. A previously validated, standardized assessment was performed before
      training, immediately after training, and then at 6 weeks, 3 months, 6 months and
      1 year for cohort 1, and before training, immediately after training, and at 6
      months and 1 year for cohort 2. All areas learned were tested for general decay.
      RESULTS: The baseline mean scores of surgical skills were 3.8/30 for instrument
      identification, 3.3/15 for one-handed knot tying, and 1.35/15 for suturing. At
      the end of the training, mean scores improved to 26.6/30, 11.2/15 and 11.1/15
      (instrument identification +599% and +772%, knot tying +447% and +417%, suturing
      +237% and +260%, respectively, for Cohort I and II). At 6 months and 1 year,
      there was a significant drop in all the three areas tested, especially in knot
      tying and suturing. There was no statistically significant difference between the
      two cohorts. CONCLUSIONS: While our surgical skills course is an effective means
      to teach surgical skills to medical students, there is significant decay in
      abilities after 6 months. Conducting regular assessments does not appear to have
      any effect in helping students retain these skills. We recommend such surgical
      skills training be conducted at appropriate intervals, such as just before
      internship, to prepare student for active surgical practice.

PMID- 30097706
TI  - Effects of Thoracic Epidural Anaesthesia on the Serosal Microcirculation of the
      Human Small Intestine.
AB  - BACKGROUND: The effect of thoracic epidural analgesia (TEA) on splanchnic blood
      flow during abdominal surgery remains unclear. The purpose of this study was to
      examine whether the hemodynamic effects of TEA resulted in microcirculatory
      alterations to the intestinal serosa, which was visualized using incident dark
      field (IDF) videomicroscopy. METHODS: An observational cohort study was
      performed. In 18 patients, the microcirculation of the intestinal serosa was
      visualized with IDF. Microcirculatory and hemodynamic measurements were performed
      prior to (T1) and after administering a bolus of levobupivacaine (T2). If
      correction of blood pressure was indicated, a third measurement was performed
      (T3). The following microcirculatory parameters were calculated: microvascular
      flow index, proportion of perfused vessels, perfused vessel density and total
      vessel density. Data are presented as median [IQR]. RESULTS: Mean arterial
      pressure decreased from 73 mmHg (68-83) at T1 to 63 mmHg (+/-11) at T2 (p =
      0.001) with a systolic blood pressure of 114 mmHg (98-128) and 87 (81-97),
      respectively (p = 0.001). The microcirculatory parameters of the bowel serosa,
      however, were unaltered. In seven patients, blood pressure was corrected to
      baseline values from a MAP of 56 mmHg (55-57), while microcirculatory parameters
      remained constant. CONCLUSION: We examined the effects of TEA on the intestinal
      serosal microcirculation during abdominal surgery using IDF imaging for the first
      time in patients. Regardless of a marked decrease in hemodynamics,
      microcirculatory parameters of the bowel serosa were not significantly affected.
      TRIAL REGISTRY NUMBER: ClinicalTrials.gov identifier NCT02688946.

PMID- 30097708
TI  - Reply to comment on "Are body mass index and performance status enough to assess
      the nutritional and functional status of elderly patients undergoing gastric
      cancer surgery?"

PMID- 30097709
TI  - 1,25-Dihydroxyvitamin D3 attenuates disease severity and induces synoviocyte
      apoptosis in a concentration-dependent manner in rats with adjuvant-induced
      arthritis by inactivating the NF-kappaB signaling pathway.
AB  - An aggressive proliferation of synoviocytes is the hallmark of rheumatoid
      arthritis (RA). Emerging evidence shows that inhibiting the NF-kappaB signaling
      pathway with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may be a therapeutic approach
      for controlling inflammatory diseases. In this study, we demonstrated the
      protective effects of three different 1,25(OH)2D3 concentration on adjuvant
      induced arthritis (AA) rats through the NF-kappaB signaling pathway and their pro
      apoptotic roles in cultured adjuvant-induced arthritis synoviocytes (AIASs). AA
      rats were prepared by injecting complete Freund's adjuvant and independently
      given daily intraperitoneal injection of 1,25(OH)2D3 at concentrations of 50,
      100, and 300 ng/day/kg. Subsequently, AIASs were isolated from the inflamed
      joints of AA rats to test the effects of 1,25(OH)2D3 on AIASs in vitro.
      Intraperitoneal injection of 1,25-(OH)2D3 was found to induce a concentration-
      and time-dependent improvement in relieving the symptoms of AA. We found an
      increased paw withdrawal thermal latency (PWTL) in the affected paw of AA rats as
      the concentration of 1,25-(OH)2D3 increased. 1,25-(OH)2D3 treatment reduced
      levels of inflammatory factors in synovial tissues of AA rats. In the case of
      cultured AIASs, 1,25-(OH)2D3 was shown to inhibit cell proliferation and induce
      cell apoptosis in a concentration-dependent manner. Additionally, 1,25-(OH)2D3
      inhibited the activation of the NF-kappaB signaling pathway. In conclusion, our
      study provides evidence emphasizing that 1,25(OH)2D3 has the potential to
      attenuate disease severity in RA potentially due to its contributory role in
      synoviocyte proliferation and apoptosis. The protective role of 1,25(OH)2D3
      against RA depends on the NF-kappaB signaling pathway.

PMID- 30097711
TI  - Spontaneous cognition in dysphoria: reduced positive bias in imagining the
      future.
AB  - Anomalies in future-oriented cognition are implicated in the maintenance of
      emotional disturbance within cognitive models of depression. Thinking about the
      future can involve mental imagery or verbal-linguistic mental representations.
      Research suggests that future thinking involving imagery representations may
      disproportionately impact on-going emotional experience in daily life relative to
      future thinking not involving imagery (verbal-linguistic representation only).
      However, while higher depression symptoms (dysphoria) are associated with
      impaired ability to deliberately generate positive relatively to negative imagery
      representations of the future (when instructed to do so), it is unclear whether
      dysphoria is associated with impairments in the tendency to do so spontaneously
      (when not instructed to deliberately generate task unrelated cognition of any
      kind). The present study investigated dysphoria-linked individual differences in
      the tendency to experience spontaneous future-oriented cognition as a function of
      emotional valence and representational format. Individuals varying in dysphoria
      level reported the occurrence of task unrelated thoughts (TUTs) in real time
      while completing a sustained attention go/no-go task, during exposure to auditory
      cues. Results indicate higher levels of dysphoria were associated with lower
      levels of positive bias in the number of imagery-based future TUTs reported,
      reflecting higher negative imagery-based future TUT generation (medium to large
      effect size), and lower positive imagery-based TUT generation (small to medium
      effect size). Further, this dysphoria-linked bias appeared to be specific in
      temporal orientation (future, not past) and representational format (imagery, not
      non-imagery). Reduced tendency to engage in positive relative to negative imagery
      based future thinking appears to be implicated in dysphoria.

PMID- 30097710
TI  - Differences in elbow extensor muscle characteristics between resistance-trained
      men and women.
AB  - PURPOSE: Muscular strength is suggested to be dependent upon muscle
      characteristics. Yet, sex-specific relationships of muscle characteristics to
      strength in the resistance-trained require investigation. Therefore, the purpose
      was to evaluate sex differences in muscle characteristics and isometric strength
      in the elbow extensors, as well as their respective associations. METHODS:
      Resistance-trained men (n = 15, mean +/- SD 22 +/- 4 years, 87.5 +/- 12.8 kg,
      16.9 +/- 2.9% body fat) and women (n = 15, mean +/- SD 25 +/- 5 years, 59.3 +/-
      7.3 kg, 22.4 +/- 4.2% body fat) were tested. B-mode ultrasound images assessed
      muscle thickness, pennation angle, and echo intensity. Muscle volume and fascicle
      length were estimated from previously validated equations. Maximal voluntary
      isometric contraction measured elbow extensors isometric strength. Independent
      samples t-tests and Fisher's r-to-z test examined differences between sexes.
      RESULTS: Sex differences existed in all muscle characteristics (p < 0.05). Men's
      absolute strength (27.86 +/- 3.55 kg) was significantly greater than women (16.15
      +/- 3.15 kg), but no differences were noted when controlling for muscle volume
      (men 0.069 +/- 0.017, women 0.077 +/- 0.022 kg/cm3). Sex differences did not
      exist in the relationships of muscle characteristics to strength with muscle size
      having the largest correlations. However, the relationship between echo intensity
      and body fat was different in men (r = - 0.311) and women (r = 0.541, p =
      0.0143). CONCLUSIONS: Sex differences in isometric elbow extensor strength are
      eliminated when expressed relative to muscle volume. Relationships of echo
      intensity and body fat were different between men and women and may be indicative
      of greater adipose infiltration in women.

PMID- 30097712
TI  - Shared attention for action selection and action monitoring in goal-directed
      reaching.
AB  - Dual-task studies have shown higher sensitivity for stimuli presented at the
      targets of upcoming actions. We examined whether attention is directed to action
      targets for the purpose of action selection, or if attention is directed to these
      locations because they are expected to provide feedback about movement outcomes.
      In our experiment, endpoint accuracy feedback was spatially separated from the
      action targets to determine whether attention would be allocated to (a) the
      action targets, (b) the expected source of feedback, or (c) to both locations.
      Participants reached towards a location indicated by an arrow while identifying a
      discrimination target that could appear in any one of eight possible locations.
      Discrimination target accuracy was used as a measure of attention allocation.
      Participants were unable to see their hand during reaching and were provided with
      a small monetary reward for each accurate movement. Discrimination target
      accuracy was best at action targets but was also enhanced at the spatially
      separated feedback locations. Separating feedback from the reaching targets did
      not diminish discrimination accuracy at the movement targets but did result in
      delayed movement initiation and reduced reaching accuracy, relative to when
      feedback was presented at the reaching target. The results suggest attention is
      required for both action planning and monitoring movement outcomes. Dividing
      attention between these functions negatively impacts action performance.

PMID- 30097714
TI  - Inhibition of Stat3 signaling pathway decreases TNF-alpha-induced autophagy in
      cementoblasts.
AB  - Autophagy is a self-digestive process that eliminates impaired or aged proteins
      and potentially toxic intracellular components to maintain homeostasis. We
      previously demonstrated that TNF-alpha played a critical role in cementoblast
      differentiation, mineralization and apoptosis; however, the effect of TNF-alpha
      on cementoblast autophagy has remained unclear. In this study, an elevated
      immunofluorescence signal of LC3B and autophagic vacuoles, autophagosomes and
      autolysosomes were detected under TNF-alpha stimulation in OCCM-30 cells.
      Autophagy-related genes and proteins, Beclin-1, LC3A and Atg-5, were
      significantly upregulated by TNF-alpha in a time- and concentration-dependent
      manner. During this process, the activity of Stat3 was dramatically enhanced and
      when the activity of Stat3 was blocked by either a specific chemical inhibitor or
      siRNA transfection before TNF-alpha stimulation, the TNF-alpha-induced
      upregulation of autophagy-related genes and proteins was strongly inhibited. Our
      results suggest that TNF-alpha induced autophagy in cementoblasts was dependent,
      or partially dependent on the activity of Stat3 signaling pathway.

PMID- 30097713
TI  - Non-participation in breast cancer screening among previous cancer patients.
AB  - PURPOSE: Breast cancer can be detected at early stages through organised
      screening. This study explored reasons for non-participation in breast cancer
      screening among previous cancer patients, who have high risk of developing a new
      primary cancer. METHOD: We conducted a population-based historical cohort study,
      including all women invited to the first organised screening round in 2008-2009
      in the Central Denmark Region (n = 149,234). All data were based on national
      registers. RESULTS: Among women with previous cancer (n = 6638), 25.3% did not
      participate in breast cancer screening compared to 20.9% of women with no
      registrations of previous cancer, thus previous cancer patients were 21% less
      likely not to participate in breast cancer screening (PRR 1.21, 95% CI 1.16
      1.27). Further analysis showed that this association was due to women receiving
      current cancer treatment or being in palliative care in the time leading up to
      screening. Women with previous malignant melanoma or colorectal cancer were more
      likely to participate in breast cancer screening, whereas women with previous
      gynaecological or "other" cancer types were less likely to participate.
      CONCLUSION: Screening for breast cancer may help diagnose breast cancer at an
      early stage. Women with previous cancer who are not undergoing current treatment
      or in palliative care have the same propensity to participate as other women
      invited to breast cancer screening. Women with previous gynaecological cancer
      were less likely to participate in breast cancer screening than women with other
      cancer types. These results may only be generalised to similar health care
      systems.

PMID- 30097715
TI  - An organic electrochemical transistor for determination of microRNA21 using gold
      nanoparticles and a capture DNA probe.
AB  - A method is described for the determination of microRNA. It is based on the use
      of organic electrochemical transistors (OECTs) fabricated on a flexible
      poly(ethylene terephthalate) substrate. A gold electrode was modified with gold
      nanoparticles to immobilize the capture DNA probe and then served as the gate of
      the device. The detection of microRNA21 was realized by monitoring the change of
      the drain-source current after hybridization of capture DNA with microRNA21.
      Under optimal conditions, this biosensor exhibits good sensitivity and
      specificity. It works in the 5 pM to 20 nM microRNA concentration range and has a
      2 pM detection limit. Graphical abstract Schematic of the organic electrochemical
      transistor-based microRNA21 biosensor. It constitutes a screen-printed carbon
      source (S) and drain (D) electrodes, a spin-coated poly(3,4
      ethylenedioxythiophere):poly(styrene sulfonic acid) (PEDOT:PSS) film on the
      poly(ethylene terephthalate) (PET) substrate, and a gold gate modified with gold
      nanoparticles (Au NPs), capture probe, and 6-mercapto-1-hexanol (MCH).

PMID- 30097716
TI  - Therapeutic efficacy of the Galletti-Contrino manoeuvre for benign paroxysmal
      positional vertigo of vertical semicircular canals in overweight subjects.
AB  - OBJECTIVE: To compare the Galletti-Contrino manoeuvre with the more widely used
      Semont-Toupet in overweight subjects presenting with benign paroxysmal positional
      vertigo (BPBV) of vertical semicircular canals (posterior and anterior canals).
      STUDY DESIGN: Prospective cohort study. PATIENTS: 204 patients (BMI range 25-30)
      with a diagnosis of BPPV of vertical semicircular canals were randomly divided in
      two groups treated with two different maneuvers: Galletti-Contrino (Group A) and
      Semont-Toupet manoeuvre (Group B). The results were compared with those obtained
      from a control group (204 non-overweight subjects with BPV of vertical
      semicircular canals.) INTERVENTION: Galletti Contrino/ Semont Toupet manoeuvres.
      MAIN OUTCOME MEASURE(S): Liberatory nystagmus or vertigo after maximum 2
      maneuvers. Vertigo and dizziness intensity scores (Visual analogue scale VAS 0
      10) from day 0 to day 5 following the repositioning manoeuvre were also recorded
      in responsive patients. RESULTS: While in non-overweight subjects no significant
      difference comparing the effectiveness of the two manoeuvres was found,
      liberatory nystagmus and vertigo were more frequently observed after Galletti
      Contrino manoeuvre in overweight subjects; this difference was statistically
      significant when posterior canals were involved (P < 0.03). Vertigo and dizziness
      VAS scores reduced significantly from day 0 to day 5 after therapy in all groups.
      A more significant reduction of dizziness VAS was recorded in patients undergoing
      Galletti-Contrino manoeuvre at days 4-5 (P < 0.005). CONCLUSION: Galletti
      Contrino manoeuvre seems to be significantly more effective than Semont-Toupet
      manoeuvre in the treatment of BPPV of posterior semicircular canal and may be
      preferential in patients with limited body movements.

PMID- 30097718
TI  - Introduction: the why and whither of genomic data sharing.

PMID- 30097717
TI  - Public perception of climatological tornado risk in Tennessee, USA.
AB  - The southeastern United States experiences some of the greatest tornado fatality
      rates in the world, with a peak in the western portion of the state of Tennessee.
      Understanding the physical and social characteristics of the area that may lead
      to increased fatalities is a critical research need. Residents of 12 Tennessee
      counties from three regions of the state (N = 1804) were asked questions about
      their perception of climatological tornado risk in their county. Approximately
      half of participants underestimated their local tornado risk calculated from 50
      years of historical tornado data. The percentage of participants underestimating
      their climatological risk increased to 81% when using model estimates of tornado
      frequencies that account for likely missed tornadoes. A mixed effects, ordinal
      logistic regression model suggested that participants with prior experience with
      tornadoes are more likely to correctly estimate or overestimate (rather than
      underestimate) their risk compared to those lacking experience (beta = 0.52, p <
      0.01). Demographic characteristics did not have a large influence on the accuracy
      of climatological tornado risk perception. Areas where more tornadoes go
      unreported may be at a disadvantage for understanding risk because residents'
      prior experience is based on limited observations. This work adds to the
      literature highlighting the importance of personal experiences in determining
      hazard risk perception and emphasizes the uniqueness of tornadoes, as they may
      occur in rural areas without knowledge, potentially prohibiting an accumulation
      of experiences.

PMID- 30097720
TI  - Pierre Mollaret (1898-1987).

PMID- 30097719
TI  - Genome-wide investigation of an ID cohort reveals de novo 3'UTR variants
      affecting gene expression.
AB  - Intellectual disability (ID) is a severe neurodevelopmental disorder with
      genetically heterogeneous causes. Large-scale sequencing has led to the
      identification of many gene-disrupting mutations; however, a substantial
      proportion of cases lack a molecular diagnosis. As such, there remains much to
      uncover for a complete understanding of the genetic underpinnings of ID. Genetic
      variants present in non-coding regions of the genome have been highlighted as
      potential contributors to neurodevelopmental disorders given their role in
      regulating gene expression. Nevertheless the functional characterization of non
      coding variants remains challenging. We describe the identification and
      characterization of de novo non-coding variation in 3'UTR regulatory regions
      within an ID cohort of 50 patients. This cohort was previously screened for
      structural and coding pathogenic variants via CNV, whole exome and whole genome
      analysis. We identified 44 high-confidence single nucleotide non-coding variants
      within the 3'UTR regions of these 50 genomes. Four of these variants were located
      within predicted miRNA binding sites and were thus hypothesised to have
      regulatory consequences. Functional testing showed that two of the variants
      interfered with miRNA-mediated regulation of their target genes, AMD1 and FAIM.
      Both these variants were found in the same individual and their functional
      consequences may point to a potential role for such variants in intellectual
      disability.

PMID- 30097721
TI  - Interpretation of HRCT Scans in the Diagnosis of IPF: Improving Communication
      Between Pulmonologists and Radiologists.
AB  - Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung
      disease (ILD). In this review, we describe the central role of high-resolution
      computed tomography (HRCT) in the diagnosis of IPF and discuss how communication
      between pulmonologists and radiologists might be improved to make the
      interpretation of HRCT scans more effective. Clinical information is important in
      the interpretation of HRCT scans, as the likelihood that specific radiologic
      features reflect IPF is not absolute, but dependent on the clinical context. In
      cases where the clinical context or HRCT pattern are inconclusive,
      multidisciplinary discussion (MDD) between a pulmonologist and radiologist (and,
      where relevant, a pathologist and rheumatologist) experienced in the differential
      diagnosis of ILD is necessary to establish a diagnosis. While it can be
      challenging to convene a face-to-face meeting, MDD can be conducted virtually or
      by telephone to enable each specialty group to contribute. To make the MDD most
      effective, it is important that relevant clinical information (for example, on
      the patient's clinical history, exposures and the results of serological tests)
      is shared with all parties in advance. A common lexicon to describe HRCT features
      observed in ILD can also help improve the effectiveness of MDD. A working
      diagnosis may be made in patients who do not fulfill all the diagnostic criteria
      for any specific type of ILD, but this diagnosis should be reviewed at regular
      intervals, with repeat of clinical, radiological, and laboratory assessments as
      appropriate, as new information pertinent to the patient's diagnosis may become
      available.

PMID- 30097723
TI  - Sex differences in predicting ADHD clinical diagnosis and pharmacological
      treatment.
AB  - In youth, ADHD is more commonly diagnosed in males than females, but higher male
      to-female ratios are found in clinical versus population-based samples,
      suggesting a sex bias in the process of receiving a clinical diagnosis of ADHD.
      This study investigated sex differences in the severity and presentation of ADHD
      symptoms, conduct problems, and learning problems in males and females with and
      without clinically diagnosed ADHD. We then investigated whether the predictive
      associations of these symptom domains on being diagnosed and treated for ADHD
      differed in males and females. Parents of 19,804 twins (50.64% male) from the
      Swedish population completed dimensional assessments of ADHD symptoms and co
      occurring traits (conduct and learning problems) when children were aged 9 years.
      Children from this population sample were linked to Patient Register data on
      clinical ADHD diagnosis and medication prescriptions. At the population level,
      males had higher scores for all symptom domains (inattention,
      hyperactivity/impulsivity, conduct, and learning problems) compared to females,
      but similar severity was seen in clinically diagnosed males and females. Symptom
      severity for all domains increased the likelihood of receiving an ADHD diagnosis
      in both males and females. Prediction analyses revealed significant sex-by
      symptom interactions on diagnostic and treatment status for
      hyperactivity/impulsivity and conduct problems. In females, these behaviours were
      stronger predictors of clinical diagnosis (hyperactivity/impulsivity: OR 1.08,
      95% CI 1.01, 1.15; conduct: OR 1.43, 95% CI 1.09, 1.87), and prescription of
      pharmacological treatment (hyperactivity/impulsivity: OR 1.24, 95% CI 1.02, 1.50;
      conduct: OR 2.20, 95% CI 1.05, 4.63). Females with ADHD may be more easily missed
      in the ADHD diagnostic process and less likely to be prescribed medication unless
      they have prominent externalising problems.

PMID- 30097724
TI  - Chemical descriptors for describing physico-chemical properties with applications
      to geosciences.
AB  - Chemical descriptors using DFT concepts characterize elements reactivity. Such
      descriptors, namely hardness and electrophilicity, are components of the
      derivative of the chemical potential. Their values form a new coordinates system,
      on which a third parameter can be mapped. The simplest mapping is the chemical
      potential itself, but other mapping may involve totally different chemical or
      physical parameters. Examples use rock analyses generated within the continental
      or oceanic crust of the Earth. They are usually described in an 11D system of
      major oxides. The new system of coordinates reduces the description to a more
      easily tractable 2D diagram. It also represents a base for plotting other
      chemical information, such as the normative component composition or a
      combination of them. Physically, other properties, such as the polymerization
      state or viscosity values, can be used to produce a 3D topography. Other
      topographic surfaces similar to the chemical potential of elements can be mapped,
      allowing quantification of partition coefficient values when elements fractionate
      in both liquid or viscous states. The reduction of an 11D diagram to a 2D one is
      suggested in other scientific descriptions of complex combinations. Graphical
      abstract [omega-eta] diagrams showing the chemical potential and the different
      continental and oceanic rock typesthen ading some chemical (Aluminium Saturation
      Index) parameter.

PMID- 30097722
TI  - Genome-wide identification and characterization of ALTERNATIVE OXIDASE genes and
      their response under abiotic stresses in Camellia sinensis (L.) O. Kuntze.
AB  - MAIN CONCLUSION: Four typical ALTERNATIVE OXIDASE genes have been identified in
      tea plants, and their sequence features and gene expression profiles have
      provided useful information for further studies on function and regulation.
      Alternative oxidase (AOX) is a terminal oxidase located in the respiratory
      electron transport chain. AOX catalyzes the oxidation of quinol and the reduction
      of oxygen into water. In this study, a genome-wide search and subsequent DNA
      cloning were performed to identify and characterize AOX genes in tea plant
      (Camellia sinensis (L.) O. Kuntze cv. Longjing43). Our results showed that tea
      plant possesses four AOX genes, i.e., CsAOX1a, CsAOX1d, CsAOX2a and CsAOX2b. Gene
      structure and protein sequence analyses revealed that all CsAOXs share a four
      exon/three-intron structure with highly conserved regions and amino acid
      residues, which are necessary for AOX secondary structures, catalytic activities
      and post-translational regulations. All CsAOX were shown to localize in
      mitochondria using the green fluorescent protein (GFP)-targeting assay. Both
      CsAOX1a and CsAOX1d were induced by cold, salt and drought stresses, and with
      different expression patterns in young and mature leaves. Reactive oxygen species
      (ROS) accumulated strongly after 72 and 96 h cold treatments in both young and
      mature leaves, while the polyphenol and total catechin decreased significantly
      only in mature leaves. In comparison to AtAOX1a in Arabidopsis thaliana, CsAOX1a
      lost almost all of the stress-responsive cis-acting regulatory elements in its
      promoter region (1500 bp upstream), but possesses a flavonoid biosynthesis
      related MBSII cis-acting regulatory element. These results suggest a link between
      CsAOX1a function and the metabolism of some secondary metabolites in tea plant.
      Our studies provide a basis for the further elucidation of the biological
      function and regulation of the AOX pathway in tea plants.

PMID- 30097726
TI  - Excellence in orthopaedic surgery: an overview of Nobel Prize nominees 1901-1960
      with focus on Friedrich Pauwels and Gerhard Kuntscher.
AB  - PURPOSE: This paper provides for the first time an overview of orthopaedic
      surgeons nominated for the Nobel Prize in physiology or medicine during the first
      six decades of the twentieth century. The study is part of the project "Enacting
      Excellency: Nobel Prize nominations for surgeons 1901-1960". METHODS: The
      nomination letters were gathered in the archive of the Nobel Committee at the
      Karolinska Institute in Solna, Sweden. RESULTS: Among the nominees, we find
      renowned scholars like Pierre Delbet, Themistocles Gluck, Gerhard Kuntscher,
      Adolf Lorenz, Friedrich Pauwels, Leslie Rush, and Marius Smith-Petersen. The
      focus of the paper is on nominations for Pauwels (work on biomechanics) and
      Kuntscher (the Kuntscher nail). Both were nominated by German surgeons.
      CONCLUSIONS: Although no orthopaedic surgeon has yet received a Nobel Prize for
      an orthopaedic achievement, Nobel archive files can help reconstruct important
      trends in the field during the twentieth century.

PMID- 30097725
TI  - Decomposition of Wolffia arrhiza residues rapidly increases mineral nitrogen and
      decreases extractable phosphorus in acidic soils.
AB  - While nutrient loads from anthropogenic sources upset aquatic ecosystem balance,
      Wolffia arrhiza (duckweed) has capacity to purge nutrient-rich water if
      continuously harvested. The nutrients accumulated in biomass have potential as
      soil fertility amendments. The objective of this study was to determine changes
      in release of nitrogen (N) and phosphorus (P), and the fate of P in soils after
      duckweed biomass amendment. An incubation experiment was conducted at 25  degrees
      C using three soils amended with proportions equivalent to 501, 1002 and 1503 mg
      N kg-1 and 62, 124 and 186 mg P kg-1. Soil samples were collected on 0, 3, 7, 14,
      21, 28, 42 and 56 days, for ammonium-N, nitrate-N and extractable-P measurements.
      At the end of incubation, P pools were determined. At least 25 mg kg-1 of
      ammonium-N was released on day 0, reaching a peak within the first 2 weeks.
      Nitrate- and mineral-N increased from 14 to 42 days, with a corresponding
      decrease in ammonium-N. Relatively fertile soil released more mineral-N at higher
      applied ratios of duckweed than the less fertile. About 10-80 mg kg-1 of duckweed
      P was extractable on day 0 and amounts progressively declined over the incubation
      period. The combined percentage (0.5%) of tissue aluminium (Al) and iron (Fe)
      facilitated Al and Fe phosphate accumulation as the proportion of duckweed
      amendment increased. The results suggested that soil type and elemental
      composition of duckweed are important determinants for N and P release, and
      liming could improve P availability in soil.

PMID- 30097728
TI  - Radial head arthroplasty: a historical perspective.
AB  - There has been lively debate regarding the rationale behind the use of radial
      head arthroplasty (RHA) for more than 80 years. Currently, its primary indication
      is for treatment of non-reconstructible RH fractures. The first RH implant,
      released in 1941, was a ferrul cap used to prevent heterotopic ossification.
      Biomechanical studies in the 1980s stimulated a revolution in RHA design by
      promoting modular implants that replicated the native bony anatomy of the elbow.
      Subsequent data-driven evolution in design led to the creation of a variety of
      devices that also accommodated for common ligamentous injuries occurring at the
      time of RH fracture. Despite significant advances in our understanding of complex
      elbow instability, improvements in implant design have to make RHA the gold
      standard for treatment of non-reconstructible RH fractures. The challenge in the
      coming years will be to perform high-level clinical studies in order to obtain
      consensus regarding the most appropriate treatment for comminuted RH fractures.

PMID- 30097727
TI  - Escherichia coli-derived BMP-2-absorbed beta-TCP granules induce bone
      regeneration in rabbit critical-sized femoral segmental defects.
AB  - PURPOSE: This study investigated whether Escherichia coli-derived bone
      morphogenetic protein (BMP)-2 (E-BMP-2) adsorbed onto beta-tricalcium phosphate
      (beta-TCP) granules can induce bone regeneration in critical-size femoral
      segmental defects in rabbits. METHODS: Bone defects 20 mm in size and stabilized
      with an external fixator were created in the femur of New Zealand white rabbits,
      which were divided into BMP-2 and control groups. E-BMP-2-loaded beta-TCP
      granules were implanted into defects of the BMP-2 group, whereas defects in the
      controls were implanted with beta-TCP granules alone. At 12 and 24 weeks after
      surgery, radiographs were obtained of the femurs and histological and
      biomechanical assessments of the defect area were performed. Bone regeneration
      was quantified using micro-computed tomography at 24 weeks. RESULTS: Radiographic
      and histologic analyses revealed bone regeneration in the BMP-2 group but not the
      control group; no fracturing of newly formed bone occurred when the external
      fixator was removed at 12 weeks. At 24 weeks, tissue mineral density, the ratio
      of bone volume to total volume, and volumetric bone mineral density of the callus
      were higher in the BMP-2 group than in control animals. In the former, ultimate
      stress, extrinsic stiffness, and failure energy measurements for the femurs were
      higher at 24 weeks than at 12 weeks. CONCLUSION: E-BMP-2-loaded beta-TCP granules
      can effectively promote bone regeneration in long bone defects.

PMID- 30097729
TI  - Assessment of anatomical and reverse total shoulder arthroplasty with the scapula
      weighted Constant-Murley score.
AB  - AIM OF THE STUDY: To evaluate total (TSA) and reverse total shoulder arthroplasty
      (RTSA) using the Constant-Murley score (CMS) and the scapula-weighted (SW) CMS,
      an integrated outcome measure that takes into account the compensatory movements
      of the scapula. METHODS: Twenty-five consecutive patients, 12 with TSA and 13
      with RTSA, underwent kinematic analysis before and after shoulder replacement.
      Measurements included flexion (FLEX) and abduction (ABD) for the humerus and
      Protraction-Retraction (PR-RE), Medio-Lateral rotation (ME-LA), and Posterior
      Anterior tilting (P-A) for the scapula. They were recorded at baseline (T0) and
      at six (T1) and 12 months (T2). Reference data were obtained from 31 control
      shoulders. RESULTS: At T1, differences in CMS and SW-CMS were not significant in
      either group, whereas values at T2 were significantly lower in RTSA patients (p =
      0.310 and p = 0.327, respectively). In TSA shoulders, the compensatory scapular
      movements in FLEX were all reduced from T0 to T2, whereas P-A was increased in
      ABD. In RTSA patients, the compensatory scapular movements in FLEX showed a
      general reduction at T1, with an increase in P-A at T2, whereas in ABD, all
      increased at T1 and decreased at T2 except for P-A, which did not decrease.
      DISCUSSION: The SW-CMS showed that the physiological scapulothoracic motion was
      not restored in TSA and RTSA patients; it may be used as a reference for the
      gradual progression of deltoid and scapular muscle rehabilitation. CONCLUSIONS:
      The worse CMS and SW-CMS scores found in RTSA patients at six months may be due
      to the biomechanics of the reverse prosthesis and to the weakness of deltoid and
      periscapular muscles.

PMID- 30097730
TI  - Occult intra-operative periprosthetic fractures of the acetabulum may affect
      implant survival.
AB  - PURPOSE: Occult intra-operative periprosthetic acetabular fracture is a seldom
      reported complication of primary total hip arthroplasty (THA). It may potentially
      be associated with cup instability and implant loosening. The present study aimed
      to investigate clinical consequences of this complication. METHODS: Between 2003
      and 2012, a total of 3390 cementless total hip arthroplasties (THA) were
      performed at our institution. Their medical histories were retrospectively
      reviewed to identify all patients who received a thin-layer computer tomography
      (CT) scan of the pelvis including the acetabulum within the first 30 post
      operative days. They were evaluated and classified by two radiologists
      independently with respect to the presence of recent acetabular fractures. All
      cases with acetabular and periacetabular fractures were included in this study.
      Electronic medical records were reviewed to assess implant revision. Cup
      stability was measured with EBRA (Einzel-Bild-Rontgen-Analyse) from plain X-rays.
      RESULTS: Periprosthetic fractures of the acetabulum were identified in 58 (50.4%)
      of 115 selected patients. Fractures close to but not including the acetabulum
      were identified in 45% (n = 26/58) of the patients, at the superolateral wall in
      17% (n = 10/58), at the anterior wall of the acetabulum in 16% (n = 9/58) and in
      10% (n = 6/58) each at the medial wall, and at the posterior wall respectively.
      One out of these 58 fractures could not be classified. Three of a total of six
      occult medial wall fractures had to be revised, and another two showed a high
      implant migration. The highest cup migration values however were found after
      fractures of the superolateral wall. Incomplete column fractures did not
      influence implant survival. CONCLUSION: Central wall acetabular fractures,
      although unrecognized intra- and post-operatively may impair implant survival
      after THA.

PMID- 30097732
TI  - Demographic pressure in Serra do Mar State Park and its buffer zone, southeastern
      Brazil.
AB  - The Serra do Mar State Park forms a green corridor that connects significant
      remnants of the Atlantic Forest in Brazil, a region that presents great
      biodiversity. However, the mounting pressure exerted on it by disorderly urban
      expansion around conservation unit areas is a cause for concern. Thereby, this
      paper aims to analyze a geographical and demographic characterization of Serra do
      Mar State Park and its buffer zone in order to identify regions under the
      greatest pressure and provide subsidies for developing public policies. The study
      is based on a cartographic representation using a geographic information system
      associated with the 2010 Census demographic data, which has been conducted by the
      Brazilian Institute of Geography and Statistics (IBGE in Portuguese acronym). The
      study area covers the territory of 32 municipalities and it was found that almost
      25,000 inhabitants live inside the park while approximately 712,000 residents
      live inside its buffer zone.

PMID- 30097733
TI  - Blockchain for Healthcare: The Next Generation of Medical Records?

PMID- 30097734
TI  - Suitability of open-access elevation models for micro-scale watershed planning.
AB  - Watershed planning is a major issue in Turkey and other parts of the world.
      Surrounded by seawater on almost three-quarters of its international borders and
      by sheer mountains along the coastal regions and throughout the country, Turkey
      experiences a range of climatic changes, which constantly shape its topography.
      Recently, the occurrences of floods, landslides, and torrents have increased,
      forcing decision-makers to come up with solutions to manage and rehabilitate the
      upper watersheds in order to stop or limit the impact of disasters on downstream
      areas. Possible solutions should reduce flow coefficients, erosion, and
      sedimentation and increase reservoir capacities. It is expected that torrent
      volumes will decrease, drainage regimes on slopes will be better organized and
      adjusted, thawing snow will be better deposited and delayed, evapotranspiration
      will increase, surface runoffs will be delayed, and water regimes will be better
      managed, meaning that flood and torrent control will be achieved. For the reasons
      mentioned above, watershed parameters need to be firmly set. In the scope of this
      study, the elevation, slope acreage, and reservoir capacity of a small watershed,
      as extracted from open-access elevation models, were compared to a real-time
      kinematic (RTK) global positioning system (GPS)-generated point cloud and the
      resulting elevation model through various geospatial and analytical means. The
      Shuttle Radar Topography Mission (SRTM) C-band digital elevation model (DEM)
      (version 3) proved to be a satisfactory method in making residual, correlation,
      mean, and reservoir capacity comparisons. An L-band Advanced Land Observing
      Satellite (ALOS) phased-array-type synthetic aperture radar (PALSAR) and an X
      band DLR_SRTM ASTER were slightly superior methods in terms of defining a greater
      number of slope categories than the other models. Finally, DLR_SRTM and SRTMv3
      could match a greater number of slope facades than the other models. Seventeen
      years after its acquisition, SRTM and its derivatives have continued leading the
      topographic definition of the Earth.

PMID- 30097731
TI  - The Genetics of Dementia with Lewy Bodies: Current Understanding and Future
      Directions.
AB  - PURPOSE OF REVIEW: Dementia with Lewy bodies (DLB) is a neurodegenerative disease
      that can be clinically and pathologically similar to Parkinson's disease (PD) and
      Alzheimer's disease (AD). Current understanding of DLB genetics is insufficient
      and has been limited by sample size and difficulty in diagnosis. The first genome
      wide association study (GWAS) in DLB was performed in 2017; a time at which the
      post-GWAS era has been reached in many diseases. RECENT FINDINGS: DLB shares risk
      loci with AD, in the APOE E4 allele, and with PD, in variation at GBA and SNCA.
      Interestingly, the GWAS suggested that DLB may also have genetic risk factors
      that are distinct from those in AD and PD. Although off to a slow start, recent
      studies have reinvigorated the field of DLB genetics and these results enable us
      to start to have a more complete understanding of the genetic architecture of
      this disease.

PMID- 30097735
TI  - Colorimetric determination of sialic acid based on boronic acid-mediated
      aggregation of gold nanoparticles.
AB  - The authors describe a rapid, sensitive and selective colorimetric assay for
      sialic acid (SA) based on the use of gold nanoparticles (AuNPs) modified with 3
      aminophenylboronic acid (3-APBA) which acts as the recognition probe for SA. 3
      APBA contains amino groups and boronic acid groups through which it can assemble
      on citrate stabilized AuNPs. It reacts with the cis-diol groups of SA by
      reversible formation of a cyclic boronate ester in slightly acidic buffer.
      Detection involves the sequential addition of AuNPs, phosphate buffer, 3-APBA and
      SA in a tube, vortex mixing, acquisition of photographic images or absorption
      spectra, and calculation of the result. The method is simple, rapid, and does not
      require cumbersome steps such as the preparation of stable boronic acid
      functionalized AuNPs as used in colorimetric sensing of saccharides. Under the
      optimum conditions, the ratio of absorbances at 700 and 520 nm increases linearly
      in the 0.15-1.00 mM SA concentrations range, and the detection limit is 60 uM.
      This is comparable to the detection limit obtained in other colorimetric assays
      reported. Acceptable intra- and inter-day precisions of three SA concentrations
      (0.50, 1.00 and 2.00 mM) ranged from 1.9-4.2% and 4.2-6.4%, respectively. The
      efficacy of the method was demonstrated by analyzing simulated human saliva which
      gave recoveries ranging from 98.7-106.0%. Graphical abstract Schematic of a
      colorimetric method for detection of sialic acid (SA) in simulated saliva. It is
      based on aggregation of gold nanoparticles with 3-aminophenyl boronic acid (3
      APBA) which assembles on AuNPs while the boronic acid group binds to cis-diols of
      SA to form a boronate ester.

PMID- 30097736
TI  - Confinement induced catalytic activity in a Diels-Alder reaction: comparison
      among various CB[n], n = 6-8, cavitands.
AB  - The impact of the size of the confining regime on the thermodynamic and kinetic
      outcome of a representative Diels-Alder reaction between ethylene and 1,3
      butadiene has been investigated in silico. To this end, two organic hosts namely
      cucurbit[6]uril (CB[6]) and cucurbit[8]uril (CB[8]) have been considered in order
      to impose confinement on the reactants/transition state/product of the concerned
      reaction. The obtained results have been compared with the recently reported
      (Chakraborty et al. ChemPhysChem 18:2162-2170, 2017) corresponding case of the
      same reaction happening inside cucurbit[7]uril (CB[7]). Results indicate that as
      compared to the reaction of ethylene and 1,3 butadiene inside CB[7], both CB[6]
      and CB[8] cavitands slow down the same reaction at 298.15 K and 1 atm. It appears
      that the size of the cavitand plays a crucial role in affecting the kinetic
      outcome of the considered reaction. While CB[7] can enforce productive alignment
      of the reactants inside its cavity thereby facilitating the reaction, neither
      CB[6] nor CB[8] can perform the same task as effectively. This situation bears
      qualitative resemblance with the cases of enzyme catalyzed reactions.

PMID- 30097738
TI  - The "Msychology" of Hypersexuality: A 40-year-old Bisexual Man's Use of Online
      Chat, Pornography, Masturbation, and Extradyadic Sex.

PMID- 30097737
TI  - Aggression among 216 patients with a first-psychotic episode of bipolar I
      disorder.
AB  - BACKGROUND: Aggression by patients with bipolar I disorder (BD-I) is not
      uncommon. Identifying potential risk factors early in the illness-course should
      inform clinical management and reduce risk. METHODS: In a study sample of 216
      initially hospitalized, first-psychotic episode subjects diagnosed with DSM-IV-TR
      BD-I, we identified recent (within 1 month before hospitalization) aggression by
      ratings on the Brief Psychiatric Rating Scale-Expanded and review of detailed
      clinical research records. We compared subjects with versus without aggressive
      behavior for associations with selected demographic and clinical factors.
      RESULTS: Aggression was identified in 23/216 subjects (10.6%). It was associated
      significantly with recent suicide attempt (OR = 4.86), alcohol abuse (OR = 3.63),
      learning disability (OR = 3.14), and initial manic episode (OR = 2.59), but not
      with age, sex, onset-type, personality disorder, time to recovery, or functional
      status. CONCLUSIONS: Among first-major episode BD-I patients with psychotic
      features, recent serious aggression towards others was identified in 10.6%. The
      odds of aggression increased by 4.9-times in association with a recent suicide
      attempt, more than 3-times with alcohol-abuse or learning disability, and by 2.6
      times if the episode polarity was manic. The findings encourage closer management
      of alcohol misuse, suicide risk, and manic symptoms, and early detection of
      learning problems in BD-I patients.

PMID- 30097740
TI  - A new approach to left sleeve pneumonectomy: complete VATS left pneumonectomy
      followed by right thoracotomy for carinal resection and reconstruction.
AB  - BACKGROUND: Left sleeve pneumonectomy is a challenging operation that requires
      individualized approaches. Here, we present a new minimally invasive combined
      thoracoscopic approach. CASE PRESENTATION: A 61-year-old woman was diagnosed with
      tracheobronchial adenoid cystic carcinoma. The tumor originated from the left
      main stem bronchus, and tumor with carinal involvement was observed. We judged
      that complete resection would be possible via left sleeve pneumonectomy. However,
      because tumor involvement with the esophagus and descending aorta was suspected,
      evaluation of resectability in advance was necessary. After confirmation via
      examination thoracoscopy of no involvement with the surrounding organs, complete
      VATS left pneumonectomy was performed and followed by right thoracotomy for
      carinal resection and reconstruction. CONCLUSIONS: When thoracoscopic surgery
      becomes mainstream, this minimally invasive combined thoracoscopic approach might
      be an optimal option for patients who require left sleeve pneumonectomy.

PMID- 30097739
TI  - Clinical Impact of Neoadjuvant Therapy on Nutritional Status in Pancreatic
      Cancer.
AB  - BACKGROUND: The association between neoadjuvant therapy (NAT) and nutritional
      status in pancreatic cancer (PC) is unknown. OBJECTIVE: The aim of this study was
      to assess the impact of NAT on nutritional status. METHODS: Overall, 161 patients
      who underwent pancreatoduodenectomy for PC between August 2010 and March 2017
      were enrolled and were divided into two groups: the neoadjuvant group (NAG; n =
      67) and the control group (CG; n = 94). Based on relative dose intensity (RDI),
      patients in the NAG group were further divided into RDI >= 80% (n = 39) and RDI <
      80% (n = 19). Changes in nutritional index, inflammatory index, and inflammation
      based prognostic scores during NAT and the perioperative period were assessed.
      RESULTS: Retinol-binding protein, prealbumin, neutrophil-to-lymphocyte ratio,
      platelet-to-lymphocyte ratio, and prognostic nutrition index significantly
      worsened in the NAG after NAT (p = 0.007, p = 0.03, p = 0.04, p = 0.007, and p =
      0.004, respectively). The recovery of rapid turnover proteins after postoperative
      day 5 was significantly worse in the NAG compared with the CG (p < 0.05), but
      tended to be more prompt in the RDI >= 80% group among the NAG. There was no
      significant difference in the incidence of postoperative complications, length of
      hospital stay, and time to postoperative adjuvant therapy between the NAG and the
      CG. CONCLUSIONS: NAT for PC could aggravate nutritional status and hamper its
      postoperative recovery. Furthermore, malnutrition might decrease tolerance of
      NAT. These findings suggest the importance of nutritional support for patients
      with NAT in PC.

PMID- 30097741
TI  - Quantitative 19F MRI of perfluoro-15-crown-5-ether using uniformity correction of
      the spin excitation and signal reception.
AB  - OBJECTIVES: A common limitation of all 1H contrast agents is that they only allow
      indirect visualization through modification of the intrinsic properties of the
      tissue, making quantification of this effect challenging. 19F compounds, on the
      contrary, are measured directly, without any background signal. There is a linear
      relationship between the amount of 19F spins and the intensity of the signal.
      However, non-uniformity of the radiofrequency field may lead to errors in the
      quantified 19F signal and should be carefully addressed for any quantitative
      imaging. MATERIALS AND METHODS: Adaptation of the previously introduced [Formula:
      see text] mapping technique to the problem of quantifying the 19F signal from
      perfluoro-15-crown-5-ether (PFCE) is proposed in this work. Initial evaluation of
      the proposed technique simultaneously accounting for transmit [Formula: see text]
      and receive [Formula: see text] field inhomogeneities is performed in a PFCE
      phantom. As a proof of concept, in vivo quantification of the 19F signal is
      performed in a murine model after application of custom-designed hollow
      mesoporous silica spheres (HMSS) loaded with PFCE. RESULTS: A phantom experiment
      clearly shows that only compensation for both transmit and receive
      characteristics outperforms inaccurate quantification based on the non- or partly
      corrected signal intensities. Furthermore, an optimized protocol is proposed for
      in vivo application. CONCLUSION: The proposed [Formula: see text]/[Formula: see
      text] mapping technique represents a simple to implement and easy-to-use solution
      for quantification of the 19F signal from PFCE in the presence of B1-field
      inhomogeneities.

PMID- 30097742
TI  - Croton golden mosaic virus: a new bipartite begomovirus isolated from Croton
      hirtus in Colombia.
AB  - A new begomovirus infecting Croton hirtus (Euphorbiaceae) from Colombia has been
      characterized. The complete DNA-A and DNA-B components were determined to be 2613
      and 2551 nt in length, respectively, showing the typical genome organization of
      bipartite New World begomoviruses. DNA-A showed the highest nucleotide sequence
      identity (81.2%) to sida yellow mottle virus (JN411687), a begomovirus isolated
      from Sida rhombifolia in Cuba. Based on the current ICTV species demarcation
      criterion for the genus Begomovirus, we report a new member of this genus
      infecting C. hirtus. We propose that it be named Croton golden mosaic virus
      (CroGMV), based on the symptoms observed in the weed. Phylogenetic analysis
      revealed that CroGMV segregates into a single clade and has some relationship
      with viruses from Central America and the Caribbean. CroGMV is the first Croton
      infecting bipartite begomovirus reported in the world.

PMID- 30097743
TI  - New polyomavirus species identified in nutria, Myocastor coypus polyomavirus 1.
AB  - A novel polyomavirus (PyVs) comprising 5,422 bp was identified by high-throughput
      sequencing (HTS) in pooled organs of nutria (Myocastor coypus). The new genome
      displays the archetypal organization of PyVs, which includes open reading frames
      for the regulatory proteins small T antigen (sTAg) and large T antigen (LTAg), as
      well as for the capsid proteins VP1, VP2 and VP3. Based on the International
      Committee on Taxonomy of Viruses (ICTV) Polyomaviridae Study Group criteria, this
      genome comprises a new PyVs species for the Alphapolyomavirus genus and is
      putatively named "Myocastor coypus Polyomavirus 1" . The complete genome sequence
      of this Myocastor coypus Polyomavirus 1 (McPyV1) isolate is publically available
      under the GenBank accession no. MH182627.

PMID- 30097744
TI  - Comparative genomics of human rubulavirus 2.
AB  - Although human rubulavirus 2 (HPIV2) is an important respiratory pathogen, little
      is known about its molecular epidemiology. We performed a comparative analysis of
      the full-length genomes of fourteen HPIV2 isolates belonging to different
      genotypes. Additionally, evolutionary analyses (phylogenetic reconstruction,
      sequence identity, detection of recombination and adaptive evolution) were
      conducted. Our study presents a systematic comparative genetic analysis that
      complements prior analyses and utilizes full-length HPIV2 genomes to provide a
      basis for future work on the clinical significance, molecular variation and
      conservation, and evolution of HPIV2.

PMID- 30097745
TI  - Genetic diversity and phylogenetic analysis of newly discovered bat astroviruses
      in Korea.
AB  - Bats have been identified as a natural reservoir for several potentially zoonotic
      viruses. Recently, astroviruses have been reported in bats in many countries, but
      not Korea. We collected 363 bat samples from thirteen species at twenty-nine
      sites in Korea across 2016 and tested them for astrovirus. The detection of the
      RNA-dependent RNA polymerase (RdRp) gene in bat astroviruses was confirmed in
      thirty-four bats across four bat species in Korea: twenty-five from Miniopterus
      fuliginosusi, one from Myotis macrodactylus, four from M. petax, and four from
      Rhinolophus ferrumequinum. The highest detection rates for astrovirus were found
      in Sunchang (61.5%, 8/13 bats), and in the samples collected in April (63.2%,
      12/19 bats). The amino acid identity of astroviral sequences identified from bat
      samples was >= 46.6%. More specifically, the amino acid identity within multiple
      clones from individual bats was >= 50.8%. Additionally, the phylogenetic topology
      between astroviruses from different bat families showed a close relationship.
      Furthermore, phylogenetic analysis of the partial ORF2 sequence of bat
      astroviruses was found to have a maximum similarity of 73.3-74.8% with available
      bat astrovirus sequences. These results indicate potential multiple-infection by
      several bat astrovirus species in individual bats, or hyperpolymorphism in the
      astrovirus strains, as well as the transmission of astroviruses across bat
      families; furthermore, our phylogenetic analysis of the partial ORF2 implied that
      a novel astrovirus may exist. However, the wide diversity of astroviral sequences
      appeared to have no significant correlation with bat species or the
      spatiotemporal distribution of Korean bat astroviruses.

PMID- 30097746
TI  - High-degree and broad-spectrum resistance mediated by a combination of NIb siRNA
      and miRNA suppresses replication of necrotic and common strains of potato virus
      Y.
AB  - In plants, viral replication can be inhibited through gene silencing, which is
      mediated by short interfering RNA (siRNA) or microRNA (miRNA). However, under
      natural conditions, viruses are extremely susceptible to mutations that may
      decrease the efficiency of cleavage of these small RNAs (sRNAs). Therefore, a
      single sRNA may not provide a sufficient degree of viral resistance to transgenic
      plants. Potato virus Y necrotic strain (PVYN) and Potato virus Y common strain
      (PVYO) are the two major PVY strains that cause systemic necrosis and mottling,
      respectively, in tobacco. In this study, we designed specific siRNAs and miRNAs
      to target two regions of the PVYO replicase gene (NIb). Eight plant expression
      vectors containing one or two sRNAs were constructed. Luciferase activity assays
      showed that the designed sRNAs successfully cleaved the NIb gene of PVYO and
      PVYN, and the vector carrying a combined siRNA- and miRNA-based short hairpin RNA
      (shRNA) demonstrated the strongest inhibitory effect. These effects were
      confirmed through the acquisition of PVYO and PVYN resistance in transgenic sRNA
      expressing Nicotiana tabacum plants. This phenomenon could be related to a plant
      defense mechanism in which siRNA and miRNA pathways are complementary and
      interact to achieve gene silencing. Furthermore, there is a tendency for the
      homologous small RNA sequences (PVYO) to be more effective in conferring
      resistance than those with imperfect homology (PVYN). Overall, these findings
      confirm that the use of a combined siRNA- and miRNA-based shRNAs is a promising
      approach for introducing viral resistance to plants through genetic engineering.

PMID- 30097747
TI  - Automatic Detection of Negated Findings in Radiological Reports for Spanish
      Language: Methodology Based on Lexicon-Grammatical Information Processing.
AB  - We present a methodology for the automatic recognition of negated findings in
      radiological reports considering morphological, syntactic, and semantic
      information. In order to achieve this goal, a series of rules for processing
      lexical and syntactic information was elaborated. This required development of an
      electronic dictionary of medical terminology and informatics grammars. Pertinent
      information for the assembly of the specialized dictionary was extracted from the
      ontology SNOMED CT and a medical dictionary (RANM, 2012). Likewise, a general
      language dictionary was also included. Lexicon-Grammar (LG), proposed by Gross
      (1975; Cahiers de l'institut de linguistique de Louvain, 24. 23-41 1998), was
      used to set up the database, which allowed an exhaustive description of the
      argument structure of predicates projected by lexical units. Computational
      framework was carried out with NooJ, a free software developed by Silberztein
      (Silberztein and Noo 2018, 2016), which has various utilities for treating
      natural language, such as morphological and syntactic grammar, as well as
      dictionaries. This methodology was compared with a Spanish version of NegEx
      (Chapman et al. Journal of Biomedical Informatics, 34(5):301-310 2001; Stricker
      2016). Results show that there are minimal differences in favor of the algorithm
      developed using NooJ, but the quality and specificity of the data improves if
      lexical-grammatical information is added.

PMID- 30097749
TI  - Intracranial arterial dolichoectasia and superficial siderosis associated to
      neurofibromatosis type 1: report of one case.

PMID- 30097750
TI  - Blunt traumatic vascular injuries of the head and neck in the ED.
AB  - Cerebrovascular injury is increasingly identified in patients presenting after
      blunt trauma due to the implementation of screening criteria and advances in
      noninvasive angiographic imaging by CT. The variable latent time before onset of
      secondary stroke presents a window of opportunity for prevention, reinforcing the
      importance of detection of asymptomatic patients via screening. Furthermore, the
      high morbidity and mortality associated with secondary stroke makes it imperative
      that radiologists recognize these challenging injuries. This article reviews the
      epidemiology of and the various proposed screening criteria for blunt
      cerebrovascular injury. The imaging findings of extra- and intracranial vascular
      injuries, including arterial and venous trauma, are reviewed along with the
      grading system. Conservative management with anticoagulation has gained favor
      over the years with intervention restricted to high-grade injuries such as
      transection and hemodynamically significant arteriovenous fistula. Many of these
      injuries also evolve over time, with or without anticoagulation, necessitating
      imaging follow-up.

PMID- 30097752
TI  - Simultaneous production of alkaline amylase and biosurfactant by Bacillus
      methylotrophicus DCS1: application as detergent additive.
AB  - This study investigated the coproduction of alkaline amylase and lipopeptides by
      Bacillus methylotrophicus DCS1 strain, as well as their biochemical
      characterisation. The best production of both amylase and biosurfactant was
      obtained when potato starch (10 g/L) and glutamic acid (5 g/L) were used as
      carbon and nitrogen sources, respectively. The bacterial strain was incubated for
      48 h at 25  degrees C and 150 rpm. This strain produced a unique amylase as
      showed by zymography technique. The optima pH and temperature were 60-65  degrees
      C and 8.0, respectively. Amylase activity was partially inhibited by EDTA (5 mM).
      The main hydrolysis products of potato starch were maltose and maltotriose. The
      alkaline amylase showed excellent stability and compatibility with various solid
      and liquid detergents. Furthermore, the biosurfactant, produced simultaneously
      with alkaline amylase, demonstrated high stability at different ranges of
      salinity, pH, and temperature. Considering its promising properties, B.
      methylotrophicus DCS1 crude extract containing both biosurfactants and amylase
      activity may be considered as a potential candidate for future use in detergent
      processing industries and environmental remediation processes.

PMID- 30097751
TI  - Growth of Dehalococcoides mccartyi species in an autotrophic consortium producing
      limited acetate.
AB  - The dechlorinating Dehalococcoides mccartyi species requires acetate as carbon
      source, but little is known on its growth under acetate limiting conditions. In
      this study, we observed growth and dechlorination of a D. mccartyi-containing
      mixed consortium in a fixed-carbon-free medium with trichloroethene in the
      aqueous phase and H2/CO2 in the headspace. Around 4 mM formate was produced by
      day 40, while acetate was constantly below 0.05 mM. Microbial community analysis
      of the consortium revealed dominance by D. mccartyi and Desulfovibrio sp. (57 and
      22% 16S rRNA gene copies, respectively). From this consortium, Desulfovibrio sp.
      strain F1 was isolated and found to produce formate and acetate (1.2 mM and 48
      uM, respectively, by day 24) when cultivated alone in the above mentioned medium
      without trichloroethene. An established co-culture of strain F1 and D. mccartyi
      strain 195 demonstrated that strain 195 could grow and dechlorinate using acetate
      produced by strain F1; and that acetate was constantly below 25 uM in the co
      culture. To verify that such low level of acetate is utilizable by D. mccartyi,
      we cultivated strain 195 alone under acetate-limiting conditions and found that
      strain 195 consumed acetate to below detection (5 uM). Based on the acetate
      consumption and cell yield of D. mccartyi, we estimated that on average 1.2 * 108
      acetate molecules are needed to supply carbon for one D. mccartyi cell. Our study
      suggests that Desulfovibrio may supply a steady but low amount of fixed carbon to
      dechlorinating bacteria, exhibiting important implications for natural bio
      attenuation when fixed carbon is limited.

PMID- 30097753
TI  - Factors hindering the implementation of surgical site infection control
      guidelines in the operating rooms of low-income countries: a mixed-method study.
AB  - The study aims to find the factors hindering the implementation of surgical site
      infection control guidelines in the operating rooms of low-income countries. The
      design of the study is a mixed-method sequential explanatory study. The setting
      is Shifa International Hospital and Pakistan Institute of Medical Sciences,
      Islamabad, Pakistan. Participants are health care workers. A questionnaire and
      structured key informant interviews probed the perspectives and perceptions of
      different stakeholders regarding the factors which hinder the implementation of
      surgical site infection control guidelines. Two-hundred fifty-two health care
      workers took part in the survey. The response rate was 90%. The majority of the
      participants was based in private teaching hospitals (63.9%) and 36.1% in the
      public sector teaching hospitals. The factors of surveillance, knowledge,
      education, and culture had low scores. Qualitative data analysis revealed the
      hindering factors in the implementation of surgical site infection control
      guidelines in the operating rooms of low-income country. The important one are
      lack of a surveillance system, education, and culture of infection control. This
      study identified hindering factors regarding implementation of surgical site
      infection control guidelines in the operating rooms at the institutional and
      individual level involved in patient care. The identification of these hindering
      factors may help politicians, policy makers, and institutions to identify the
      strategies for overcoming these hindering factors. Education is the key factor
      for success. By offering training to health care workers, we significantly
      contribute to decrease the incidence of SSIs in the low-income country.

PMID- 30097754
TI  - Age- and height-adjusted total kidney volume growth rate in autosomal dominant
      polycystic kidney diseases.
AB  - BACKGROUND: The Mayo Clinic Image Classification (MIC) was proposed as a renal
      prognosis prediction model for autosomal dominant polycystic kidney disease
      (ADPKD). MIC is based on the assumption of exponential constant increase in
      height-adjusted total kidney volume (HtTKV). HtTKV growth rate is calculated by
      one-time measurement of HtTKV and age. We named it as an age-adjusted HtTKV
      growth rate (AHTKV-alpha). AHTKV-alpha was compared with HtTKV slope measured by
      at least two HtTKV values. METHODS: Comparison of repeatability between AHTKV
      alpha and HtTKV slope, correlation of subgroups divided according to baseline
      AHTKV-alpha and HtTKV slope with disease manifestations, estimated glomerular
      filtration rate (eGFR) slope, and renal survival were analyzed in 296 patients
      with ADPKD. PKD genotype influences were compared between AHTKV-alpha and HtTKV
      slope in 88 patients with characterized PKD mutations. RESULTS: Absolute
      differences between baseline and follow-up measures were significantly larger for
      the HtTKV slope than for AHTKV-alpha (P < 0.0001). From baseline AHTKV-alpha
      based subgroups A-E according to MIC, disease manifestations occurred earlier and
      future eGFR slopes became steeper (P < 0.0001). Multivariate hazard ratios of
      renal survival differed significantly among baseline AHTKV-alpha-based subgroups.
      Inter-subgroup differences in these predictors were less evident during baseline
      HtTKV slope-based classification. AHTKV-alpha values, but not HtTKV slopes, were
      significantly higher for PKD1 mutation carriers than for PKD2 mutation carriers
      (P < 0.0001). CONCLUSION: MIC is a good renal prediction model applicable to
      Japanese patients also. AHTKV-alpha can be a more sensitive and reliable
      indicator in TKV growth rate than HtTKV slope.

PMID- 30097748
TI  - Potential applications of engineered nanoparticles in medicine and biology: an
      update.
AB  - Nanotechnology advancements have led to the development of its allied fields,
      such as nanoparticle synthesis and their applications in the field of
      biomedicine. Nanotechnology driven innovations have given a hope to the patients
      as well as physicians in solving the complex medical problems. Nanoparticles with
      a size ranging from 0.2 to 100 nm are associated with an increased surface to
      volume ratio. Moreover, the physico-chemical and biological properties of
      nanoparticles can be modified depending on the applications. Different
      nanoparticles have been documented with a wide range of applications in various
      fields of medicine and biology including cancer therapy, drug delivery, tissue
      engineering, regenerative medicine, biomolecules detection, and also as
      antimicrobial agents. However, the development of stable and effective
      nanoparticles requires a profound knowledge on both physico-chemical features of
      nanomaterials and their intended applications. Further, the health risks
      associated with the use of engineered nanoparticles needs a serious attention.

PMID- 30097756
TI  - Twice-daily red and blue light treatment for Candida albicans biofilm matrix
      development control.
AB  - Phototherapy has been proposed as a direct means of affecting local bacterial
      infections. However, the use of phototherapy to prevent fungal biofilm
      development has received comparatively less attention. This study aimed to
      determine the effects of red light treatment and blue light treatment, without a
      photosensitizer, on the development of Candida albicans biofilm. During the
      development of 48-h biofilms of C. albicans SN 425 (n = 10), the biofilms were
      exposed twice-daily to noncoherent blue and red light (LumaCare; 420 nm and 635
      nm). The energy density applied was 72 J cm-2 for blue light and 43.8 J cm2, 87.6
      J cm2, and 175.5 J cm2 for red light. Positive control (PC) and negative control
      (NC) groups were treated twice-daily for 1 min with 0.12% chlorhexidine (CHX) and
      0.89% NaCl respectively. Biofilms were analyzed for colony forming units (CFU),
      dry-weight, and exopolysaccharides (EPS-soluble and EPS-insoluble). Data was
      analyzed by one-way ANOVA and Tukey post hoc test (alpha = 0.05). Dry-weight was
      lower than NC (p < 0.001) and approached PC levels with both red and blue light
      treatments. CFU were also lower in groups exposed to blue light and higher
      durations of red light (p < 0.05). EPS-soluble and EPS-insoluble measures were
      variably reduced by these light exposures. In conclusion, twice-daily exposure to
      both blue and red lights affect the biofilm development and physiology of
      polysaccharide production and are potential mechanisms for the control of C.
      albicans biofilm matrix development.

PMID- 30097755
TI  - Triggers of NLRC4 and AIM2 inflammasomes induce porcine IL-1beta secretion.
AB  - Pigs are an important livestock and serve as a large animal model due to
      physiological and anatomical similarities with humans. Thus, components of the
      porcine immune system such as inflammasomes need to be characterized for disease
      control, vaccination, and translational research purposes. Previously, we and
      others elucidated porcine nucleotide-binding oligomerization domain (NOD)-like
      receptor (NLR) family Pyrin domain containing 3 (NLRP3) inflammasome activation.
      However, until now, porcine NLR family caspase recruitment domain (CARD)
      containing 4 (NLRC4) and absent in melanoma 2 (AIM2) inflammasomes have been not
      well studied. In this study, we treated well defined NLRC4 and AIM2 inflammasome
      triggers to porcine peripheral blood mononuclear cells (PBMCs) and murine bone
      marrow derived macrophages (BMDMs) and observed interleukin (IL)-1beta maturation
      as a readout of inflammasome activation. NLRC4 (flagellin) and AIM2 (dsDNA)
      triggers led to IL-1beta secretion in both porcine PBMCs and mice macrophages. In
      addition, porcine and mouse NLRC4 and AIM2 inflammasomes responded differently to
      NLRP3 inhibitors. Bacterial inflammasome triggers, Salmonella enterica serovar
      Typhimurium, Listeria monocytogenes, and Escherichia coli, also induced IL-1beta
      secretion in porcine PBMCs. Taken together, we suggest that known triggers of
      NLRC4 and AIM2 inflammasomes in mice induce IL-1beta secretion in porcine PBMCs.

PMID- 30097757
TI  - Treatment of erythematotelangiectatic rosacea, facial erythema, and facial
      telangiectasia with a 577-nm pro-yellow laser: a case series.
AB  - Various lasers have been used for the treatment of erythematotelangiectatic
      rosacea (ETR), facial erythema (FE), and facial telangiectasias (FT). The
      assessment of the treatments of all of these conditions with a 577-nm pro-yellow
      laser has not been reported yet. The aim of this work was to assess the efficacy
      and safety of the 577-nm pro-yellow laser in ETR, FE, and FT. Forty patients
      suffering from ETR, FE, and FT (25 female and 15 male) were enrolled in this
      study. All of the patients were treated with 577-nm pro-yellow laser
      (QuadroStarPRO YELLOW(r) Asclepion Laser Technologies, Germany) at 4-week
      intervals, for one to four sessions. The assessment of the treatment was made
      based on the digital photographs and the percentage of fading of the erythema and
      telangiectasias in the lesions. Significant clinical improvement (80-100%) was
      observed in the first or second sessions of the treatment in FE and ETR patients
      and in second and fourth sessions of the treatment in FT patients. The treatment
      was very well tolerated. No side effect was observed except for a few patients
      who had mild to moderate erythema fading away in 12-24 h. This case series has
      shown that the pro-yellow laser is a very effective, safe, and well-tolerated
      treatment for ETR, FE, and FT.

PMID- 30097759
TI  - Vagal Tone as a Putative Mechanism for Pragmatic Competence: An Investigation of
      Carriers of the FMR1 Premutation.
AB  - Pragmatic language skills exist across a continuum in typical and clinical
      populations, and are impaired in many neurodevelopmental disorders, most notably
      autism. The mechanisms underlying pragmatic impairment are poorly understood,
      although theory suggests dampened vagal tone plays a role. This study
      investigated the FMR1 premutation as a genetic model that may lend insight into
      the relationship between vagal function and pragmatic ability. Participants
      included 38 women with the FMR1 premutation and 23 controls. Vagal tone accounted
      for significant variance in pragmatics across both groups and statistically
      mediated the effect of FMR1 premutation status on pragmatic ability. Results
      support vagal tone as a biophysiological correlate of pragmatic ability, which
      informs potential mechanistic underpinnings and could have implications for
      targeted treatment.

PMID- 30097758
TI  - A novel genetic marker of decreased inflammation and improved survival after
      acute myocardial infarction.
AB  - The CHRNA5 gene encodes a neurotransmitter receptor subunit involved in multiple
      processes, including cholinergic autonomic nerve activity and inflammation.
      Common variants in CHRNA5 have been linked with atherosclerotic cardiovascular
      disease. Association of variation in CHRNA5 and specific haplotypes with
      cardiovascular outcomes has not been described. The aim of this study was to
      examine the association of CHRNA5 haplotypes with gene expression and mortality
      among patients with acute myocardial infarction (AMI) and explore potential
      mechanisms of this association. Patients (N = 2054) hospitalized with AMI were
      genotyped for two common variants in CHRNA5. Proportional hazard models were used
      to estimate independent association of CHRNA5 haplotype with 1-year mortality.
      Both individual variants were associated with mortality (p = 0.0096 and 0.0004,
      respectively) and were in tight LD (D' = 0.99). One haplotype, HAP3, was
      associated with decreased mortality one year after AMI (adjusted HR = 0.42, 95%
      CI 0.26, 0.68; p = 0.0004). This association was validated in an independent
      cohort (N = 637) of post-MI patients (adjusted HR = 0.23, 95% CI 0.07, 0.79; p =
      0.019). Differences in CHRNA5 expression by haplotype were investigated in human
      heart samples (n = 28). Compared with non-carriers, HAP3 carriers had threefold
      lower cardiac CHRNA5 mRNA expression (p = 0.023). Circulating levels of the
      inflammatory marker hsCRP were significantly lower in HAP3 carriers versus non
      carriers (3.43 +/- 4.2 versus 3.91 +/- 5.1; p = 0.0379). Activation of the
      inflammasome, an important inflammatory complex involved in cardiovascular
      disease that is necessary for release of the pro-inflammatory cytokine IL-1 beta,
      was assessed in bone marrow-derived macrophages (BMDM) from CHRNA5 knockout mice
      and wild-type controls. In BMDM from CHRNA5 knockout mice, IL-1beta secretion was
      reduced by 50% compared to wild-type controls (p = 0.004). Therefore, a common
      haplotype of CHRNA5 that results in reduced cardiac expression of CHRNA5 and
      attenuated macrophage inflammasome activation is associated with lower mortality
      after AMI. These results implicate CHRNA5 and the cholinergic anti-inflammatory
      pathway in survival following AMI.

PMID- 30097760
TI  - Applying Eye Tracking to Identify Autism Spectrum Disorder in Children.
AB  - Eye tracking (ET) holds potential for the early detection of autism spectrum
      disorder (ASD). To overcome the difficulties of working with young children,
      developing a short and informative paradigm is crucial for ET. We investigated
      the fixation times of 37 ASD and 37 typically developing (TD) children ages 4-6
      watching a 10-second video of a female speaking. ASD children showed significant
      reductions in fixation time at six areas of interest. Furthermore, discriminant
      analysis revealed fixation times at the mouth and body could significantly
      discriminate ASD from TD with a classification accuracy of 85.1%, sensitivity of
      86.5%, and specificity of 83.8%. Our study suggests that a short video clip may
      provide enough information to distinguish ASD from TD children.

PMID- 30097763
TI  - Reckoning with the last enemy.
AB  - Developing the ethics of palliative sedation, particularly in contrast to
      terminal sedation, requires consideration of the relation between body and soul
      and of the nature of death and dying. Christianly considered, it also requires
      attention to the human vocation to immortality and hence to the relation between
      medicine (as aid for the body) and discipline (as aid to the soul). Leaning on
      Augustine's rendering of the latter, this paper provides a larger anthropological
      and soteriological frame of reference for the ethics of palliative sedation,
      organized by way of nine briefly expounded theses. It argues that palliative
      sedation, like other elements of medicine, is appropriate where, and only where,
      it properly orders care for the body to the requirements of care for the soul.

PMID- 30097762
TI  - Salt stress in rice: multivariate analysis separates four components of
      beneficial silicon action.
AB  - How many subcellular targets of the beneficial silicon effect do exist in salt
      stressed rice? Here, we investigate the effects of silicon on the different
      components of salt stress, i.e., osmotic stress, sodium, and chloride toxicity.
      These components are separated by multivariate analysis of 18 variables measured
      in rice seedlings (Oryza sativa L.). Multivariate analysis can dissect vectors
      and extract targets as principal components, given the regressions between all
      variables are known. Consequently, the exploration of 153 correlations and 306
      regression models between all variables is essential, and regression parameters
      for variables of shoot (silicon, sodium, chloride, carotenoids, chlorophylls a
      and b, and relative growth rate) and variables of shoot and root (hydrogen
      peroxide, ascorbate peroxidase (APX), catalase (CAT), fresh weight, dry weight,
      root-to-shoot ratio) are determined. The regression models [log (y) = y0 + a *
      log (x)] are confirmed by variance analysis of global goodness of fits (p <
      0.0001). Thereby, logarithmic transformation yields linearization for
      multivariate analysis by Pearson's correlation. Four principal components are
      extracted: two targets of osmotic stress, one target of sodium toxicity, and one
      target of chloride toxicity. Thereby, silicon improves salt tolerance by
      increasing APX and CAT activities and decreasing hydrogen peroxide, salt ion
      accumulation, photosynthetic pigment losses, and growth inhibition. Salt stress
      increases silicon uptake pointing to a physiological regulation of plant salt
      stress in the presence of silicon. This mechanism and its four components are
      promising targets for further agricultural application.

PMID- 30097765
TI  - Delayed childbearing and female ageing impair assisted reproductive technology
      outcome in survivors of male haematological cancers.
AB  - PURPOSE: To analyse the impact of female characteristics on assisted reproductive
      technology outcome among male haematological cancer survivors. METHODS: A
      retrospective analysis of 93 haematological cancer survivors attending our
      tertiary referral fertility centre between June 1998 and June 2017 for achieving
      fatherhood with assisted reproductive technology treatments. RESULTS: A
      progressive increase in the median female age was observed during the study
      period (32.2 years until the year 2007 and 36.9 years from the year 2012). Fifty
      five out of 93 patients were treated with intracytoplasmic sperm injection (ICSI)
      (113 ovarian stimulations, 108 ICSI procedures). Cryopreserved ejaculated sperm
      was used in 28 couples, fresh sperm in 19, and thawed testicular sperm in 8
      couples. Mean female age at ovarian stimulation was 37.0 +/- 4.7 years. Twenty
      six pregnancies resulted in a full-term birth (23% per started ovarian
      stimulation; 43.6% per couple) and 33 children were born. No significant
      differences were observed according to source of sperm (fresh, frozen,
      testicular) and multivariate analysis confirmed that maternal age was the only
      variable inversely related to the cumulative delivery rate, being five times
      lower (15.7%) when the female partner was >= 40 years (OR = 0.22, 95% CI 0.06
      0.77) vs. 58.3% with younger women (p = 0.0037). CONCLUSIONS: Delayed
      childbearing and female ageing affect ICSI outcome in couples where the male is a
      survivor of haematological cancer. This topic should be discussed when
      counselling male cancer patients about fertility preservation.

PMID- 30097766
TI  - Seven new resin glycosides from the seeds of Quamoclit * multifida.
AB  - Seven new resin glycosides, multifidins III (1)-IX (7), were isolated from the
      seeds of Quamoclit * multifida (syn. Q. sloteri House) (Convolvulaceae), along
      with five known glycosides, quamoclinic acid B methyl ester (8), operculin XIII
      (9), quamoclin I (10), QM-10 (11), and QM-12 (12). Their structures were
      determined on the basis of spectroscopic data and chemical evidence. These
      compounds were of two different types, i.e., those with macrolactone structures
      and those with non-macrolactone structures. Additionally, cytotoxic activity
      towards HL-60 human leukemia cells of 1, 2, 5, 8, 9, 11, and 12 was evaluated.
      Among them, macrolactone-type resin glycosides (jalapins), 1, 2, and 9,
      specifically demonstrated clear cytotoxic activity with IC50 values of 3.46,
      14.7, and 10.9 MUM, respectively.

PMID- 30097761
TI  - Social Function and Autism Spectrum Disorder in Children and Adults with
      Neurofibromatosis Type 1: a Systematic Review and Meta-Analysis.
AB  - In light of the proliferation of recent research into social function in
      neurofibromatosis type 1 (NF1), a systematic review and meta-analysis is required
      to synthesise data and place findings within the context of a theoretical
      framework. This paper reviews findings from research into social function and
      autism spectrum disorder (ASD) in children and adults with NF1 and integrates
      these findings with the Socio-Cognitive Integration Abilities Model (SOCIAL). It
      also critically appraises links between social outcomes, internal and external
      factors moderating social functioning, cognitive domains implicated in social
      functioning, and underlying neural pathology in NF1. A systematic literature
      search conducted in MedLine (Ovid), PsycINFO (Ovid), Embase (Ovid), and PubMed
      electronic databases yielded 35 papers that met inclusion criteria for the
      systematic review. Out of these papers, 22 papers provided sufficient data for
      meta-analysis. Findings from this review and meta-analysis provide evidence that
      children and adults with NF1 exhibit significantly higher prevalence and severity
      of social dysfunction and ASD symptomatology. To date, very few studies have
      examined social cognition in NF1 but results indicate the presence of both
      perceptual and higher-level impairments in this population. The results of this
      review also provide support for age, gender, and comorbid ADHD as moderating
      factors for social outcomes in NF1. Suggestions for future research are offered
      to further our understanding of the social phenotype in NF1 and to facilitate the
      development of targeted interventions.

PMID- 30097767
TI  - Investigating the structural properties of the active conformation BTL2 of a
      lipase from Geobacillus thermocatenulatus in toluene using molecular dynamic
      simulations and engineering BTL2 via in-silico mutation.
AB  - The discovery or development of thermoalkalophilic lipases that show high levels
      of catalytic activity in organic solvents would have important industrial
      ramifications. However, this goal is yet to be achieved because organic solvents
      induce structural changes in lipases that suppress their catalytic abilities. A
      deep understanding of these structural changes to lipases in the presence of
      organic solvents is required before strategies can be devised to stop them from
      occurring. In this work, we investigated the effects of an organic reaction
      medium, toluene, on the structure of the Bacillus thermocatenulatus lipase BTL2
      using MD simulation. The main aims were to identify the regions of the protein
      that are particularly sensitive to the presence of an organic solvent, and how
      the presence of a hydrophobic medium affects the overall stability of the enzyme.
      Upon analyzing how the behavior of the enzyme differed in aqueous and hydrophobic
      media, it was found that many significant zones of the protein suffer in the
      presence of an organic solvent, which increases the rigidity of the system. This
      was readily apparent when we investigated important noncovalent interactions
      (salt bridges) and probed how distances between the atoms of the catalytic triad
      Ser114, Asp318, and His359 change in the presence of toluene. Moreover, the high
      tendency for the system to destabilize in toluene was explained by the results of
      FoldX calculations. Calculations showed that the addition of a small amount of
      water to the hydrophobic reaction environment should restore the required
      flexibility of BTL2. The insights gained from the analysis of our simulations
      allowed us to propose a modification of BTL2, the G116P mutation, that should
      result in the structural behavior of BTL2 in organic solvent being closer to that
      of BTL2 in water.

PMID- 30097768
TI  - Particular Levels of Odors Released by Virgin Females Attract Conspecific Males
      of the Funnel-Web Spider Allagelena difficilis.
AB  - Female-released chemical signals are crucial clues for mate-searching males to
      locate and gain sexual receptivity of conspecific females. Abundant behavioral
      evidence indicates that female spiders release sex pheromones to guide mate
      searching behavior of conspecific mature males. However, the chemical nature of
      spider pheromones is poorly understood. Females of the funnel-web spider,
      Allagelena difficilis, employ sit-and-wait tactics for mating. Field observations
      indicate that males leave their retreats to search for potential mates during the
      breeding season. Therefore, we investigated whether virgin females release a sex
      attractant to conspecific males and then explored the chemical nature of the
      female pheromone. Four fatty acids extracted from the female bodies (palmitic
      acid, linoleic acid, cis-vaccenic acid and stearic acid) constitute a multiple
      component sex attractant to conspecific males in A. difficilis. Unexpectedly,
      mated females also produce the same fatty acids, but at trace levels. Two-choice
      experiments showed that males were significantly attracted by the blend of the
      four fatty acids in appropriate concentrations while avoiding the blend
      consisting of the same acids at very low concentrations, suggesting that mate
      searching males are able to discriminate virgin females from mated females by the
      quantities of female-specific fatty acids in the funnel-web spider A. difficilis.

PMID- 30097770
TI  - The Endosomal Network: Mediators and Regulators of Endosome Maturation.
AB  - Endocytosis is a means for the cell to sample its environment for nutrients and
      regulate plasma membrane (PM) composition and area. Whereas the majority of
      internalized cargo is recycled back to the cell surface, select material is sent
      to the lysosome for degradation. Endosomes further play major roles in central
      cell activities as diverse as establishment of cell polarity and signaling,
      lysosomal storage and immunity. The complexity of endosomal functions is
      reflected by the extensive changes to endosome properties as they mature. The
      identity of individual endosomes is influenced by the presence of specific Rab
      GTPases and phosphoinositides (PIPs), which coordinate membrane traffic and
      facilitate endosomal functions. Motors and tethers direct the endosomes to the
      required locations and moderate fusion with other organelles. The maintenance of
      the elaborate endosomal network is supported by the ER and the trans-Golgi
      network (TGN), which promote the exchange of membrane components, provide
      enzymes, and assist with signaling. Additionally, V-ATPase is emerging as an
      underappreciated coordinator of endosome maturation and cell signaling. The
      inputs of the various mediators of endosome maturation are tightly regulated and
      coordinated to ensure appropriate maintenance and functioning of endosomes at
      each stage of the maturation process. Perturbations in endosome maturation are
      implicated in devastating diseases, such as neurodegeneration and cancer, and the
      endosome maturation processes are manipulated and exploited by intracellular
      pathogens to meet their own needs. A greater understanding of coordination and
      fine-tuning of endosome maturation will help us address various pathologies more
      effectively.

PMID- 30097769
TI  - Plasma prolactin levels are associated with the severity of illness in drug-naive
      first-episode psychosis female patients.
AB  - Patients with schizophrenia frequently present hyperprolactinemia as a
      consequence of antipsychotic treatment. However, an increase in circulating
      prolactin levels has also been shown in patients without previous treatment. Our
      objective was to compare prolactin levels between antipsychotic-naive first
      episode psychosis (AN-FEP) patients and healthy controls (HC). As part of an FEP
      program (Programa Asistencial Fases Iniciales de Psicosis [PAFIP]), 270 AN-FEP
      patients and 153 HC were eligible for this study. Serum prolactin levels were
      measured by an automated immunochemiluminescent assay. Subjects' sex and having
      an AN-FEP diagnosis both had an effect on prolactin levels, with higher levels in
      women than in men, and in AN-FEP patients than in HC. Moreover, plasma prolactin
      levels showed a negative correlation with the SAPS scores in AN-FEP female
      patients. AN-FEP patients have increased levels of prolactin, which might be
      stress-induced. This, together with the association of higher prolactin with a
      lower severity of the disease, suggests that prolactin might play a
      neuroprotective role, especially in women.

PMID- 30097771
TI  - Integration of the Endocytic System into the Network of Cellular Functions.
AB  - Maintenance of physiologic cellular functions and homeostasis requires highly
      coordinated interactions between different cellular compartments. In this regard,
      the endocytic system, which plays a key role in cargo internalization and
      trafficking within the cell, participates in upkeep of intracellular dynamics,
      while communicating with multiple organelles. This chapter will discuss the
      function of endosomes from a standpoint of cellular integration. We will present
      examples of different types of interactions between endosomes and other cellular
      compartments, such as the endoplasmic reticulum (ER), mitochondria, the plasma
      membrane (PM), and the nuclear envelope. In addition, we will describe the
      incorporation of endocytic components, such as endosomal sorting complexes
      required for transport (ESCRT) proteins and Rab small GTPases, into cellular
      processes that operate outside of the endolysosomal pathway. The significance of
      endosomal interactions for processes such as signaling regulation, intracellular
      trafficking, organelle dynamics, metabolic control, and homeostatic responses
      will be reviewed. Accumulating data indicate that beyond its involvement in cargo
      transport, the endocytic pathway is comprehensively integrated into other systems
      of the cell and plays multiple roles in the complex net of cellular functions.

PMID- 30097772
TI  - GTPases Rac1 and Ras Signaling from Endosomes.
AB  - The endocytic compartment is not only the functional continuity of the plasma
      membrane but consists of a diverse collection of intracellular heterogeneous
      complex structures that transport, amplify, sustain, and/or sort signaling
      molecules. Over the years, it has become evident that early, late, and recycling
      endosomes represent an interconnected vesicular-tubular network able to form
      signaling platforms that dynamically and efficiently translate extracellular
      signals into biological outcome. Cell activation, differentiation, migration,
      death, and survival are some of the endpoints of endosomal signaling. Hence, to
      understand the role of the endosomal system in signal transduction in space and
      time, it is therefore necessary to dissect and identify the plethora of decoders
      that are operational in the different steps along the endocytic pathway. In this
      chapter, we focus on the regulation of spatiotemporal signaling in cells,
      considering endosomes as central platforms, in which several small GTPases
      proteins of the Ras superfamily, in particular Ras and Rac1, actively participate
      to control cellular processes like proliferation and cell mobility.

PMID- 30097773
TI  - ESCRT and Membrane Protein Ubiquitination.
AB  - The ubiquitin-dependent degradation of membrane proteins via the multivesicular
      body (MVB) pathway requires the Endosomal Sorting Complexes Required for
      Transport (ESCRT). This molecular machinery is composed of five distinct multi
      subunit complexes. On the surface of endosomes, ESCRT-0, -I and -II bind to
      ubiquitinated membrane proteins, while ESCRT-III and Vps4 bud intraluminal
      vesicles (ILVs) into the lumen of the endosomes. By working together, ESCRTs
      package membrane proteins into ILVs and thereby generate MVBs. The fusion of
      mature MVBs with lysosomes delivers ILVs into the lysosomal lumen where the
      membrane proteins are degraded. Besides generating ILVs, the ESCRT machinery
      mediates for topologically related membrane budding processes at the plasma
      membrane and the nuclear envelop. In this chapter, we briefly discuss membrane
      protein ubiquitination, endocytosis, and summarize current knowledge on the ESCRT
      machinery in the MVB pathway.

PMID- 30097774
TI  - Retromer and Its Role in Regulating Signaling at Endosomes.
AB  - The retromer complex is a key element of the endosomal protein sorting machinery
      being involved in trafficking of proteins from endosomes to the Golgi and also
      endosomes to the cell surface. There is now accumulating evidence that retromer
      also has a prominent role in regulating the activity of many diverse signaling
      proteins that traffic through endosomes and this activity has profound
      implications for the functioning of many different cell and tissue types from
      neuronal cells to cells of the immune system to specialized polarized epithelial
      cells of the retina. In this review, the protein composition of the retromer
      complex will be described along with many of the accessory factors that
      facilitate retromer-mediated endosomal protein sorting to detail how retromer
      activity contributes to the regulation of several distinct signaling pathways.

PMID- 30097775
TI  - The Lysosome and Intracellular Signalling.
AB  - In addition to being the terminal degradative compartment of the cell's endocytic
      and autophagic pathways, the lysosome is a multifunctional signalling hub
      integrating the cell's response to nutrient status and growth factor/hormone
      signalling. The cytosolic surface of the limiting membrane of the lysosome is the
      site of activation of the multiprotein complex mammalian target of rapamycin
      complex 1 (mTORC1), which phosphorylates numerous cell growth-related substrates,
      including transcription factor EB (TFEB). Under conditions in which mTORC1 is
      inhibited including starvation, TFEB becomes dephosphorylated and translocates to
      the nucleus where it functions as a master regulator of lysosome biogenesis. The
      signalling role of lysosomes is not limited to this pathway. They act as an
      intracellular Ca2+ store, which can release Ca2+ into the cytosol for both local
      effects on membrane fusion and pleiotropic effects within the cell. The
      relationship and crosstalk between the lysosomal and endoplasmic reticulum (ER)
      Ca2+ stores play a role in shaping intracellular Ca2+ signalling. Lysosomes also
      perform other signalling functions, which are discussed. Current views of the
      lysosomal compartment recognize its dynamic nature. It includes endolysosomes,
      autolysosome and storage lysosomes that are constantly engaged in fusion/fission
      events and lysosome regeneration. How signalling is affected by individual
      lysosomal organelles being at different stages of these processes and/or at
      different sites within the cell is poorly understood, but is discussed.

PMID- 30097776
TI  - Interplay of Endocytosis and Growth Factor Receptor Signalling.
AB  - Growth factor receptors play a variety of roles during embryonic development and
      in adult homeostasis. These receptors are activated repeatedly in different
      cellular contexts and with different cellular outcomes. This begs the question as
      to how cells in a particular developmental, spatial and temporal context, or in
      adult tissue, interpret signalling by growth factor receptors in order to deliver
      qualitatively different signalling outputs. One mechanism by which this could
      occur is via endocytic regulation. The original paradigm for the role of
      endocytosis in growth factor receptor signalling was that receptor uptake has a
      quantitative role in signalling by reducing the number of cell surface receptors
      available for activation and targeting activated receptors for degradation.
      However, a range of studies over the last several years, in many different
      experimental systems, has demonstrated an additional qualitative role for
      endocytic trafficking in receptor signalling, with specific outcomes depending on
      the location of the signalling complex. Confinement of receptors within endosomes
      can spatially regulate signalling, facilitating specific protein interactions or
      post-translational modifications that alter throughout the trafficking process.
      Therefore, endocytosis does not simply regulate cell surface expression, but
      tightly controls protein interactions and function to produce distinct outcomes.

PMID- 30097777
TI  - Role of the Endocytosis of Caveolae in Intracellular Signaling and Metabolism.
AB  - Caveolae are 60-80 nm invaginated plasma membrane (PM) nanodomains, with a
      specific lipid and protein composition, which assist and regulate multiple
      processes in the plasma membrane-ranging from the organization of signalling
      complexes to the mechanical adaptation to changes in PM tension. However, since
      their initial descriptions, these structures have additionally been found tightly
      linked to internalization processes, mechanoadaptation, to the regulation of
      signalling events and of endosomal trafficking. Here, we review caveolae biology
      from this perspective, and its implications for cell physiology and disease.

PMID- 30097778
TI  - EGFR Trafficking in Physiology and Cancer.
AB  - Signaling from the epidermal growth factor receptor (EGFR) elicits multiple
      biological responses, including cell proliferation, migration, and survival.
      Receptor endocytosis and trafficking are critical physiological processes that
      control the strength, duration, diversification, and spatial restriction of EGFR
      signaling through multiple mechanisms, which we review in this chapter. These
      mechanisms include: (i) regulation of receptor density and activation at the cell
      surface; (ii) concentration of receptors into distinct nascent endocytic
      structures; (iii) commitment of the receptor to different endocytic routes; (iv)
      endosomal sorting and postendocytic trafficking of the receptor through distinct
      pathways, and (v) recycling to restricted regions of the cell surface. We also
      highlight how communication between organelles controls EGFR activity along the
      endocytic route. Finally, we illustrate how abnormal trafficking of EGFR
      oncogenic mutants, as well as alterations of the endocytic machinery, contributes
      to aberrant EGFR signaling in cancer.

PMID- 30097779
TI  - Evolving View of Membrane Trafficking and Signaling Systems for G Protein-Coupled
      Receptors.
AB  - The G protein-coupled receptor (GPCR) superfamily activates complex signal
      pathways, yet untangling these signaling systems to understand how specificity in
      receptor signaling pathways is achieved, has been a challenging question. The
      roles of membrane trafficking in GPCR signal regulation has undergone a recent
      paradigm shift, from a mechanism that programs the plasma membrane G protein
      signaling profile to providing distinct signaling platforms critical for
      specifying receptor function in vivo. In this chapter, we discuss this evolution
      of our understanding in the endocytic trafficking systems employed by GPCRs, and
      how such systems play a deeply integrated role with signaling. We describe recent
      studies that suggest that the endomembrane compartment can provide a mechanism to
      both specify, and yet also diversify, GPCR signal transduction. These new
      evolving models could aid mechanistic understanding of complex disease and
      provide novel therapeutic avenues.

PMID- 30097780
TI  - Endosomal Trafficking During Mitosis and Notch-Dependent Asymmetric Division.
AB  - Endocytosis is key in a number of cell events. In particular, its role during
      cell division has been a challenging question: while early studies examined
      whether endocytosis occurs during cell division, recent works show that, during
      division, cells do perform endocytosis actively. More importantly, during
      asymmetric cell division, endocytic pathways also control Notch signaling:
      endocytic vesicles regulate the presence, at the plasma membrane, of receptors
      and ligands at different levels between the two-daughter cells. Both early and
      late endocytic compartments have been shown to exert key regulatory controls by
      up-regulating or down-regulating Notch signaling in those cells. This biased
      Notch signaling enable finally cell fate assignation and specification which play
      a central role in development and physiology. In this chapter, we cover a number
      of significant works on endosomal trafficking evincing the importance of
      endocytosis in Notch-mediated cell fate specification during development.

PMID- 30097781
TI  - Midwifery Students' Perceptions of Spirituality and Spiritual Care: An Example
      from Western Turkey.
AB  - This cross-sectional study aimed to explore Turkish midwifery students'
      perceptions of spirituality and spiritual care and to investigate the factors
      affecting them. Data were collected from 271 students of the Midwifery Department
      of the High School of Health of a state university in the west of Turkey using
      the Spirituality and Spiritual Care Rating Scale. A significant difference was
      found between belief in the need for spiritual care and the practice of spiritual
      care during midwifery training and the total score on the Spirituality and
      Spiritual Care Rating Scale, but no significant difference was found between the
      students' year of class, whether they had heard about spiritual care, and their
      state of knowledge concerning spiritual care. An increase in awareness, knowledge
      and skills relating to spirituality and spiritual care on the part of midwifery
      students, who are the midwives of the future, will allow students to provide
      spiritual care to their patients after they qualify. For this reason, the
      education program of midwifery students should be seen from a holistic standpoint
      in order to develop spiritual care.

PMID- 30097782
TI  - Lower Circulating Androgens Are Associated with Overall Cancer Risk and Prostate
      Cancer Risk in Men Aged 25-84 Years from the Busselton Health Study.
AB  - Androgens, notably testosterone (T), have been implicated in development of
      several common cancers and prostate cancer; however, precise mechanisms remain
      unclear. This study assessed prospective associations of serum T,
      dihydrotestosterone (DHT) and estradiol (E2) with overall cancer (excluding skin
      cancer), prostate, colorectal and lung cancer risk in 1574 community-dwelling men
      aged 25-84 years. Sex hormones were assayed using mass spectrometry and men were
      followed for 20 years with outcomes ascertained using data linkage. Over 20
      years, there were 289, 116, 48 and 22 men who developed any cancer, prostate
      cancer, colorectal cancer and lung cancer, respectively. Androgens in the lowest
      quartile were associated with an increased overall cancer risk (HR = 1.36, 95% CI
      1.05-1.76, p = 0.020 for T; and HR = 1.30, 95% CI 1.00-1.69, p = 0.049 for DHT
      comparing the lowest vs other quartiles). T in the lowest quartile was associated
      with an increased risk of prostate cancer (HR = 1.53, 95% CI 1.02-2.29, p = 0.038
      comparing the lowest vs other quartiles). The association between androgens and
      overall cancer risk remained similar after excluding prostate cancer outcomes;
      however, results were not significant. There were no associations of T, DHT or E2
      with colorectal or lung cancer risk; however, LH in the highest quartile was
      associated with an increased risk of lung cancer (HR = 4.55, 95% CI 1.70-12.19, p
      = 0.003 for the highest vs other quartiles). Whether T is a biomarker of poor
      health in men with any cancer or prostate cancer requires further confirmation as
      does the nature and mechanism of the association of a high LH with future lung
      cancer.

PMID- 30097783
TI  - Half-time photodynamic therapy in treatment of chronic central serous
      chorioretinopathy.
AB  - PURPOSE: Different modes of photodynamic therapy (PDT) were described for
      treatment of central serous chorioretinopathy (CSC). The purpose of the current
      study was to evaluate the outcome of half-time PDT in chronic CSC. METHODS: A
      retrospective case series study, including 114 eyes of 103 patients with chronic
      CSC, treated with reduced-fluence PDT. PDT was applied with full-dose verteporfin
      (6 mg/m2) and half-time fluence (43 s). The main outcome measures included timing
      of complete subretinal fluid (SRF) resolution, recurrences, pre- and post
      treatment best-corrected visual acuities (BCVA). Anatomical and functional
      effects were compared in subgroup analysis on the basis of CSC treatment
      efficacy. Subsequent analysis was performed to compare eyes with and without
      recurrences and CSC eyes treated by single and multiple PDT sessions. RESULTS: A
      total of 114 eyes of 103 patients (81 male; 22 female) were analyzed. The median
      age was 49 (28-70). The median CSC pretreatment duration was 12 months (3-393).
      The median follow-up period after PDT was 8 months (6-111). By the sixth-month
      period PDT was effective in 80% (91 eyes), with a subsequent enhancement up to
      87% (99 eyes) at 12th month and not effective in 13% (15 eyes). SRF resolution
      was achieved after 8 weeks (2-44) with a significant improvement of median LogMAR
      BCVA from 0.22 (- 0.2-1.3) before PDT to 0.1 (- 0.2-1.0) at last visit after PDT
      (p < 0.0001). CONCLUSIONS: Half-time PDT has proven to be an effective and safe
      treatment option for patients with chronic CSC with a significant BCVA
      improvement during the follow-up after the therapy.

PMID- 30097784
TI  - The characteristics of digenic familial exudative vitreoretinopathy.
AB  - AIM: To describe and analyse the clinical and genetic characteristics of digenic
      familial exudative vitreoretinopathy (FEVR). METHODS: The study cohort consisted
      of patients with FEVR (n = 13) to identify patients with two mutations in two
      different genes. A genetic analysis of the LRP5, FZD4, TSPAN12, and ZNF408 genes
      was performed with next-generation sequencing (NGS). The genotype data obtained
      from the patients with FEVR were analysed and correlated with their clinical
      manifestations. They were then further evaluated in conjunction with other data
      that were available for these genes. The probands and parents/relatives underwent
      comprehensive age-appropriate ophthalmic examinations. RESULTS: The medical
      history and genetic reports of 487 patients with FEVR were reviewed. In all, we
      identified 13 probands (2.67%, 13/487) with simultaneous mutations in two disease
      causing genes. A total of 25 of mutations were found, including10 in FZD4, 8 in
      LRP5, 3 in ZNF408, 2 in NDP, and 2 in TSPAN12. The most frequent mutations were
      those in FZD4 and LRP5. We identified 8 mutations that had previously been
      identified and 17 novel variants. Among 26 eyes, 65.38% exhibited a phenotype,
      and 10 (38.46%) were stage 4, while 7 (26.92%) were stage 5. CONCLUSIONS: This is
      the first study to report a group of patients with digenic FEVR. In most affected
      eyes, the stage was more severe than stage 3. We speculate that the phenotype of
      FEVR is more severe in patients with digenic rather than monogenic variants of
      FEVR-related genes.

PMID- 30097786
TI  - Dietary Patterns in Chinese Americans are Associated with Cardiovascular Disease
      Risk Factors, the Chinese American Cardiovascular Health Assessment (CHA CHA).
AB  - Little is known about the dietary patterns of Chinese Americans. Understanding
      their dietary patterns can provide insights for addressing cardiovascular disease
      (CVD) risk among Chinese American immigrants. The objective of this study was to
      identify dietary patterns among Chinese American immigrants living in New York
      City (NYC) and to describe associations with demographic and CVD risk factors. A
      validated Food Frequency Questionnaire assessed usual dietary intake in Chinese
      American immigrants living in NYC as part of the Chinese American Cardiovascular
      Health Assessment (CHA CHA) in 2010-2011 (n = 1973, age range 21-89 years).
      Principal components analysis with varimax rotation retaining three factors with
      eigenvalues > 1.5 identified dietary patterns. Multivariable linear regression
      models tested associations between CVD risk factors and dietary pattern scores.
      In multivariable analyses, each unit of increase in the Sweets factor was
      associated with 0.76 +/- 0.33 (mean +/- SD) mg/dL higher HDL cholesterol and a
      6.2 +/- 2.7% increase in HOMA-IR. In contrast, each unit increase in the Fried
      Noodles factor was associated with a 0.27 +/- 0.11 inch greater waist
      circumference, - 0.89 +/- 0.40 mg/dL lower HDL cholesterol, and also a 6.9 +/-
      2.6% increase in HOMA-IR. Each unit increase in the Vegetables factor was
      associated with a - 1.40 +/- 0.43 mmHg and - 0.95 +/- 0.27 mm Hg decrease in
      systolic and diastolic blood pressure, respectively. Dietary patterns are
      significantly associated with CVD risk factors among Chinese American immigrants
      in NYC. Future work will inform how dietary patterns relate to level of
      acculturation in order to guide the development of dietary interventions to
      reduce CVD risk.

PMID- 30097785
TI  - Incidence and risk factors for neovascular age-related macular degeneration in
      the fellow eye.
AB  - PURPOSE: The epidemiology, risk factors, and the effect of anti-VEGF treatment on
      neovascular age-related macular degeneration (nAMD) have primarily been studied
      in the first eye developing the disease. The understanding of pathophysiology and
      planning of follow-up examinations can be improved by knowledge of incidence and
      risk factors for development of the disease in the fellow eye. METHODS: In a
      prospective observational cohort study, epidemiological and clinical risk factors
      for the development of nAMD in the fellow eye among 2516 patients consecutively
      diagnosed with the disease from a population of 0.9 million citizens during a
      period of more than 10 years were studied. RESULTS: nAMD had been diagnosed in
      the fellow eye of 541 (21.5%) of the patients. The incidence of fellow-eye
      involvement increased from approximately 5% in patients initially presenting with
      bilateral disease to approximately 28% more than 6 years after the diagnosis in
      the first eye. Visual acuity (VA) was higher and central retinal thickness (CRT)
      was lower in fellow eyes with nAMD diagnosed later than the first eye. Male
      gender, increasing leakage area, and peripapillary location of the subretinal
      neovascular membrane in the first eye reduced the risk of developing disease in
      the fellow eye. CONCLUSIONS: The planning of follow-up examinations of patients
      diagnosed with nAMD in one eye should consider that the risk of fellow-eye
      involvement is higher within the first 6 years, in women, and when the leakage
      area in the first eye is small and not located peripapillary.

PMID- 30097787
TI  - Statistical modelling for optimized lyophilization of Lactobacillus acidophilus
      strains for improved viability and stability using response surface methodology.
AB  - The awareness regarding use of probiotics for health benefits has created a huge
      market worldwide. The use of probiotic cultures and its success in commercial
      scale is relying on the techniques employed to ensure that the potential cultures
      with desired functional activity are stable and viable for longer period. The
      present study was undertaken to statistically evaluate the effect of
      lyoprotectant in the suspension media containing sucrose and reconstituted skim
      milk on the viability of Lactobacillus acidophilus strains. The central composite
      rotatable design of response surface methodology was used in evaluating the
      survival rate and viability even after 24 months' storage of three different
      lyophilized strains of L. acidophilus. We also determined the exclusive use of
      lyoprotectant on the survival of the lyophilized strains throughout the study
      period without altering any of the culture conditions. The most conspicuous
      result to emerge from the data is that the suspension medium composed of minimal
      amount of sucrose (~ 1.2%) in the reconstituted skim milk (6%) was evident in
      maintaining a higher survival rate of lyophilized culture during 2-year storage.
      From this investigation, the optimized suspension media used to obtain the
      lyophilized concentrate of L. acidophilus could be recommended in designing
      dietary supplement with minimal modification for industrial application. This
      might reduce the manufacturing cost as well as storage loss occurring both in
      pharma and food sector.

PMID- 30097788
TI  - Utility of acute arrhythmia termination as an ablation endpoint for induced
      atrial tachyarrhythmia after complete pulmonary vein isolation during catheter
      ablation for persistent atrial fibrillation.
AB  - PURPOSE: The presence of inducible atrial tachyarrhythmia after pulmonary vein
      isolation (PVI) during radiofrequency catheter ablation (RFCA) for persistent
      atrial fibrillation (AF) may indicate the necessity of further substrate
      modification, but the optimal ablation endpoint is unknown. We sought to assess
      the impact of procedural termination of inducible atrial tachyarrhythmia after
      PVI in comparison with continued atrial tachyarrhythmia after PVI. METHODS: Among
      patients who underwent RFCA for persistent AF, we enrolled 93 patients who were
      in sinus rhythm after PVI and had inducible atrial tachyarrhythmia and 157
      patients with continued atrial tachyarrhythmia after PVI. The impact of acute
      arrhythmia termination during further substrate modification on recurrence was
      compared between the two groups. RESULTS: Acute termination was achieved in 51
      (54.8%) patients in the induced arrhythmia group and 61 (38.9%) in the continued
      arrhythmia group. During a mean 35.8 months, acute termination did not
      significantly reduce arrhythmia recurrence in the induced arrhythmia group (HR
      0.712, 95% CI 0.400-1.266, p = 0.247), while it was associated with improved
      outcome in the continued arrhythmia group (HR 0.590, 95% CI 0.355-0.979, p =
      0.038). Acute termination of either induced atrial tachycardia (AT) or induced AF
      was not associated with improved procedure outcome. Among the continued
      arrhythmia group, the benefit of acute termination was statistically significant
      in AT (HR 0.329, 95% CI 0.108-0.997, p = 0.039), but not in AF (HR 0.704, 95% CI
      0.396-1.253, p = 0.233) after PVI. CONCLUSIONS: Acute termination of induced
      rhythm is not a reliable ablation endpoint during substrate modification in
      patients with inducible arrhythmia after PVI.

PMID- 30097790
TI  - Correction to: Prognostic influence of prior chronic obstructive pulmonary
      disease in patients admitted for their first episode of acute heart failure.
AB  - In the original publication, the given name and family name of the fifth author
      Dr Margherita Migone De Amicis were incorrectly published. The correct given name
      and family name should read as 'Margherita' and 'Migone De Amicis', respectively.

PMID- 30097789
TI  - The effects of septal myectomy and alcohol septal ablation for hypertrophic
      cardiomyopathy on the cardiac conduction system.
AB  - AV conduction abnormalities are observed in 15-30% of patients with hypertrophic
      cardiomyopathy but are usually not severe enough to require permanent pacemaker
      implant. Both septal myectomy and alcohol septal ablation are effective options
      to relieve symptoms due to left ventricular outflow tract gradient in patients
      with hypertrophic cardiomyopathy but have procedure-specific effects on AV
      conduction and the His Purkinje system. Septal myectomy is associated with the
      development of LBBB in 50-100% of patients, while alcohol septal ablation is
      associated with RBBB in 37-70% of patients. Baseline abnormalities in the
      contralateral bundles and the presence of conduction disease have an important
      impact on the likelihood of the development of AV block for both of these
      therapies. AV block requiring permanent pacing occurs in approximately 2-3% of
      patients after septal myectomy and 10-15% of patients after alcohol septal
      ablation. Permanent pacemaker implant after alcohol septal ablation is more
      common in older patients (> 55 years old 13 vs. < 55 years old 5%; p = 0.06).
      Improved outcomes for septal myectomy and alcohol septal ablation are observed in
      experienced centers. Septal reduction therapies should be performed at medical
      centers with a dedicated hypertrophic cardiomyopathy program using a
      multidisciplinary approach.

PMID- 30097792
TI  - Examining potential gaps in supportive medication use for US and foreign-born
      Hispanic women with breast cancer.
AB  - BACKGROUND: Compared to non-Hispanic Whites, Hispanic women are more likely to
      report pain, depression, and other mental health concerns. However, little is
      known about Hispanic women's use of supportive medications, and whether use
      differs depending on nativity (US- vs. foreign-born). This study's objectives
      were to examine patterns of supportive medication use and investigate potential
      differences by ethnicity/nativity among women with breast cancer. METHODS: We
      used the Surveillance, Epidemiology, and End Results data linked with Medicare
      claims to identify women diagnosed with incident breast cancer between July 1,
      2007, and December 31, 2011. Supportive medication use (opioid pain and non
      opioid psychotropic medications) in the 90 days after diagnosis was the primary
      outcome. We categorized ethnicity/nativity as US-Born non-Hispanic, US-born
      Hispanic, foreign-born non-Hispanic, and foreign-born Hispanic. Modified Poisson
      models examined associations between ethnicity/nativity and medication use,
      adjusting for tumor, treatment, and demographic characteristics. RESULTS: We
      included 23,091 women, of whom 88% were US-born non-Hispanics, 4% US-born
      Hispanics, 6% foreign-born non-Hispanics, and 2% foreign-born Hispanics.
      Supportive medication use varied by ethnicity/nativity. Compared to US-born non
      Hispanics, foreign-born Hispanics and non-Hispanics were 5% (95% CI 0.92-0.98)
      and 10% (95% CI 0.85-0.96) less likely to receive supportive medications,
      respectively. US-born Hispanics were 5% (95% CI 1.02-1.09) more likely to receive
      supportive medications. Observed differences persisted when analyses were limited
      to stage I-III breast cancer cases. CONCLUSIONS: This work highlights potential
      disparities in the pharmacologic treatment of psychosocial needs of foreign-born
      breast cancer patients. Future studies should explore if differences observed
      here are reflective of health disparities or differential patient preferences.

PMID- 30097791
TI  - Pupillary response: cognitive effort for breast cancer survivors.
AB  - PURPOSE: The purpose of this cross-sectional comparative pilot study was to
      evaluate cognitive effort, indexed by pupillary response (PR), for breast cancer
      survivors (BCS) with complaints of cognitive dysfunction following chemotherapy.
      STUDY AIMS: Compare the cognitive effort employed by BCS to healthy controls (HC)
      during neuropsychological tests (NPT) for memory, sustained attention, verbal
      fluency, visuospatial ability, processing speed and executive function; and
      Investigate the relationship between PR-indexed cognitive effort and
      participants' self-report of cognitive function. METHODS: Self-report of
      cognitive function was collected from 23 BCS and 23 HC. PR was measured during
      NPT. Independent two-sample t tests or Wilcoxon rank sum tests were used to
      compare group scores. Between-group effect size (Cohen's d) was calculated for
      each outcome. Correlation between mean self-report scores and PR values, as well
      as 95% confidence intervals, was calculated. RESULTS: No group differences were
      demonstrated for NPT performance. BCS reported more issues with cognitive
      function than HC (p < .0001). A group effect for BCS was seen with PR-indexed
      cognitive effort for components of most NPT (p < .05). PR was correlated with
      most self-report measures of cognitive function (r = 0.33-0.45). CONCLUSIONS: PR
      sensitivity to cognitive effort across a variety of NPT and correlation with self
      report of cognitive function was demonstrated. The portability, affordability,
      and "real-time" aspects of PR are attractive for potential use in the clinic
      setting to assess cognitive function. A larger study is needed to confirm these
      results. Prospective investigation of PR in BCS is needed to demonstrate
      sensitivity to cognitive function changes over time.

PMID- 30097794
TI  - Machine learning and feature selection for drug response prediction in precision
      oncology applications.
AB  - In-depth modeling of the complex interplay among multiple omics data measured
      from cancer cell lines or patient tumors is providing new opportunities toward
      identification of tailored therapies for individual cancer patients. Supervised
      machine learning algorithms are increasingly being applied to the omics profiles
      as they enable integrative analyses among the high-dimensional data sets, as well
      as personalized predictions of therapy responses using multi-omics panels of
      response-predictive biomarkers identified through feature selection and cross
      validation. However, technical variability and frequent missingness in input "big
      data" require the application of dedicated data preprocessing pipelines that
      often lead to some loss of information and compressed view of the biological
      signal. We describe here the state-of-the-art machine learning methods for anti
      cancer drug response modeling and prediction and give our perspective on further
      opportunities to make better use of high-dimensional multi-omics profiles along
      with knowledge about cancer pathways targeted by anti-cancer compounds when
      predicting their phenotypic responses.

PMID- 30097795
TI  - The Association of Anesthesia Clinical Directors (AACD) Glossary of Times Used
      for Scheduling and Monitoring of Diagnostic and Therapeutic Procedures.
AB  - The Glossary of Times Used for Scheduling and Monitoring of Diagnostic and
      Therapeutic Procedures also known as the Procedural Times Glossary (PTG) was
      originally developed with the support of the Association of Anesthesia Clinical
      Directors (AACD). The goal was to establish standardized terms to measure and
      assess the performance of operating room and procedural areas. By incorporating
      standardized concepts of efficiency and utilization, the PTG codified operating
      room metrics and facilitated benchmarking and quality improvement initiatives. In
      the last three decades, these concepts have also served as the basis for research
      in operating room management, including incorporating frameworks from diverse
      fields. The metrics in the PTG are divided into four categories: (1) Procedural
      Times; (2) Procedural and Scheduling Definitions and Time Periods; (3)
      Utilization and Efficiency Indices; and (4) Patient Categories. We describe each
      of the categories and corresponding metrics. The PTG provides the fundamental
      building blocks for managing operating and non-operating room suites. We hope
      that reintroducing these important time markers will help facilitate the
      reporting of standardized metrics.

PMID- 30097796
TI  - Prophylactic mesh used in ileal conduit formation following radical cystectomy: a
      retrospective cohort.
AB  - PURPOSE: Given the difficulty of durable repairs, there is continued interest in
      hernia prevention. One emerging prevention technique for parastomal hernias is
      prophylactic mesh placement, whereby mesh is inserted during the index procedure
      as hernia prophylaxis. We evaluated our experience using prophylactic mesh when
      creating an ileal conduit. METHODS: We retrospectively reviewed patients
      undergoing robotic cystectomy with ileal conduit from 6/2010 to 8/2017. Patient
      demographics and operative/perioperative outcomes were documented. We evaluated
      hernia recurrence using postoperative computed tomography scanning or physical
      exam. Prophylactic mesh was inserted at the operating surgeon's discretion using
      a synthetic resorbable or biologic mesh. RESULTS: During the study period, 38
      patients underwent robotic-assisted cystectomy with ileal conduit formation.
      Average patient age was 68 years, with 28 (74%) male and 35 (92%) Caucasian
      patients. Three patients (8%) required conversion to open, and one patient (3%)
      had a concomitant colorectal resection. Thirty-one (88%) patients had
      postoperative computed tomography scanning. Prophylactic mesh was used in 18
      patients (47%) in a retrorectus position. Of these, 15 (83%) patients had
      synthetic resorbable mesh and 3 (17%) patients had biologic mesh. At average
      follow-up of 21 months, one hernia recurred (5%) in a patient without mesh
      placement at the time of ileal conduit. At an average follow-up of 11 months,
      there have been no recurrences and no mesh-related complications in the
      prophylactic mesh group. CONCLUSIONS: Using prophylactic mesh in ileal conduit,
      creation is feasible and may decrease the parastomal hernia formation rate.
      Further study of using synthetic resorbable and biologic meshes for hernia
      prophylaxis is warranted.

PMID- 30097799
TI  - Proceedings of the First Vietnamese-French Joint Conference on Applications of
      Mathematics to Ecology, Bio-economics, Epidemiology and Health Care: Hanoi and
      Tuanchau, Vietnam, December 12-15, 2016.

PMID- 30097798
TI  - Thickness Dependence on Interfacial and Electrical Properties in Atomic Layer
      Deposited AlN on c-plane GaN.
AB  - The interfacial and electrical properties of atomic layer deposited AlN on n-GaN
      with different AlN thicknesses were investigated. According to capacitance
      voltage (C-V) characteristics, the sample with a 7.4-nm-thick AlN showed the
      highest interface and oxide trap densities. When the AlN thickness was 0.7 nm, X
      ray photoelectron spectroscopy (XPS) spectra showed the dominant peak associated
      with Al-O bonds, along with no clear AlN peak. The amount of remained oxygen
      atoms near the GaN surface was found to decrease for the thicker AlN. However,
      many oxygen atoms were present across the AlN layer, provided the oxygen-related
      defects, which eventually increased the interface state density. The barrier
      inhomogeneity with thermionic emission (TE) model was appropriate to explain the
      forward bias current for the sample with a 7.4-nm-thick AlN, which was not proper
      for the sample with a 0.7-nm-thick AlN. The reverse leakage currents for both the
      samples with 0.7- and 7.4-nm-thick AlN were explained better using Fowler
      Nordheim (FN) rather than Poole-Frenkel emissions.

PMID- 30097797
TI  - Immunization with Chlamydia psittaci plasmid-encoded protein CPSIT_p7 induces
      partial protective immunity against chlamydia lung infection in mice.
AB  - The present study evaluated the immune-protective efficacy of the Chlamydia
      psittaci (C. psittaci) plasmid protein CPSIT_p7 and analyzed the potential
      mechanisms of this protection. The current study used recombinant CPSIT_p7
      protein with Freund's complete adjuvant and Freund's incomplete adjuvant to
      vaccinate BALB/c mice. Adjuvants alone or PBS formulated with the same adjuvants
      was used as negative controls. Mice were intranasally challenged with 105
      inclusion-forming units (IFU) of C. psittaci. We found that CPSIT_p7 vaccination
      significantly decreased the mouse lung chlamydial load, interferon-gamma (IFN
      gamma) level, and pathological injury. This protection correlated well with
      specific humoral and cellular immune responses against C. psittaci. In vitro or
      in vivo neutralization of C. psittaci with sera harvested from immunized mice did
      not reduce the number of recoverable C. psittaci in the infected lungs, but CD4+
      spleen cells collected from CPSIT_p7-immunized mice significantly decreased the
      chlamydial load via adoptive transfer to native mice. These results reveal that
      the protection conferred by CPSIT_p7 is dependent on CD4+ T cells.

PMID- 30097800
TI  - A Convenient and Effective Method to Deposit Low-Defect-Density nc-Si:H Thin Film
      by PECVD.
AB  - Hydrogenated nanocrystalline silicon (nc-Si:H) thin film has received a great
      deal of attention as a promising material for flat panel display transistors,
      solar cells, etc. However, the multiphase structure of nc-Si:H leads to many
      defects. One of the major challenges is how to reduce the defects conveniently.
      In this work, we developed a simple and effective method to deposit low-defect
      density nc-Si:H thin film. This method is simply by tuning the deposition
      pressure in a high-pressure range in plasma-enhanced chemical vapor deposition
      (PECVD) process. Microstructures of the nc-Si:H were characterized by Raman, AFM,
      and SEM. Furthermore, we focused on the defect density which was the key
      characteristic for photovoltaic materials and achieved the defect density of
      3.766 * 1016 cm-3. This defect density is lower than that of previous studies on
      the fabrication of low-defect-density nc-Si:H by other complex methods in PECVD
      process. The minority carrier lifetime of nc-Si:H is thus greatly improved.
      Moreover, we demonstrated the mechanism about the effect of deposition pressure
      on the ion bombardment and proved that the defect density is the key
      characteristic for nc-Si:H photovoltaic material.

PMID- 30097801
TI  - Correction to: Efficient derivation of extended pluripotent stem cells from NOD
      scid Il2rg-/- mice.
AB  - In the original publication Fig. 1D and supplementary material is incorrect. The
      correct figure and supplementary material is provided in this correction.

PMID- 30097802
TI  - Anti-Neuroinflammatory Effects of Vanillin Through the Regulation of Inflammatory
      Factors and NF-kappaB Signaling in LPS-Stimulated Microglia.
AB  - Microglia, resident macrophages of the central nervous system (CNS), is
      responsible for immune responses and homeostasis of the CNS. Microglia plays a
      complex role in neuroinflammation, which has been implicated in neurodegenerative
      diseases such as Alzheimer's disease and Parkinson's disease. Therefore,
      therapeutic agents that suppress the microglia-mediated inflammatory response
      could potentially be used in the prevention or treatment of neurodegenerative
      diseases. Vanillin, a primary component of vanilla bean extract, has anti
      inflammatory, anticancer, and antitumor properties. However, the effects of
      vanillin on the anti-neuroinflammatory responses of microglial cells are still
      poorly understood. In this study, we investigated the mechanism by which vanillin
      induces anti-neuroinflammatory responses in lipopolysaccharide (LPS)-stimulated
      BV-2 microglial cells. We found that vanillin significantly decreased the
      production of nitric oxide and pro-inflammatory cytokines, including interleukin
      (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6).
      Vanillin also reduced the protein levels of inducible nitric oxide synthase
      (iNOS) and cyclooxygenase-2 (COX-2), as well as the mRNA expression levels of IL
      1beta, TNF-alpha, and IL-6. Moreover, vanillin inhibited the phosphorylation of
      mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-kappaB.
      Collectively, these results suggest that vanillin has anti-neuroinflammatory
      properties and may act as a natural therapeutic agent for neuroinflammatory
      diseases.

PMID- 30097804
TI  - The 117th Annual Scientific Meeting of the American Society of Colon and Rectal
      Surgeons.

PMID- 30097803
TI  - Indocyanine green fluorescence angiography during low anterior resection for low
      rectal cancer: results of a comparative cohort study.
AB  - BACKGROUND: Anastomotic leak (AL) after low anterior resection (LAR) is
      associated with increased morbidity, mortality, cost and cancer recurrence rates.
      The aim of this study was to evaluate the impact of fluorescence angiography (FA)
      on AL following LAR for low rectal cancer. METHODS: This is a single surgeon
      retrospective cohort study with a historical, consecutively sampled case matched
      control group. The institution's prospectively maintained institutional review
      board (IRB)-approved database was queried for all patients who underwent a
      laparoscopic LAR for rectal neoplasia with a colorectal or coloanal anastomosis <
      5 cm from the anal verge between 2013 and 2016. Patients were divided into two
      groups: patients in whom FA was employed (study group, 2015-2016) and those
      patients in whom it was not (control group, 2013-2015). All patients were
      diverted with a loop ileostomy. The primary outcome measured was the AL rate and
      the secondary outcome measured was change in surgical plan following FA. RESULTS:
      Sixty patients were included in the study: 30 patients in the FA group and 30
      patients in the control group. Patients' demographics, the use of neoadjuvant
      chemoradiation, tumor stage, and mean height of anastomosis were comparable
      between the study groups. FA led to a change in surgical plan in four patients
      (13.3%) none of who suffered an AL. Two patients in the control group had a
      clinically and radiologically confirmed AL, whereas there were no leaks in the FA
      group (6.7% vs. 0%, p = 0.49). CONCLUSIONS: FA changed the surgical plan in 13.3%
      of LAR's, potentially reducing the incidence of AL in these high-risk patients.

PMID- 30097805
TI  - Probability of bivariate superiority: A non-parametric common-language statistic
      for detecting bivariate relationships.
AB  - Researchers often focus on bivariate normal correlation (r) to evaluate bivariate
      relationships. However, these techniques assume linearity and depend on
      parametric assumptions. We propose a new nonparametric statistical model that can
      be more intuitively understood than the conventional r: probability of bivariate
      superiority (PBS). Our development of Bp, the estimator of a PBS relationship,
      extends Dunlap's (1994) common-language transformation of r (CLr) by providing a
      method to directly estimate PBS-the probability that when x is above (or below)
      the mean of all X, its paired y score will also be above (or below) the mean of
      all Y. Probability of superiority is an important form of bivariate relationship
      that until now could only be accurately estimated when data met the parametric
      assumptions for r. We specify the copula that forms the theoretical basis for
      PBS, provide an algorithm for estimating PBS from a sample, and describe the
      results of a Monte Carlo experiment that evaluated our algorithm across 448 data
      conditions. The PBS estimate, Bp, is robust to violations of parametric
      assumptions and offers a useful method for evaluating the significance of
      probability-of-superiority relationships in bivariate data. It is critical to
      note that Bp estimates a different form of bivariate relationship than does r.
      Our working examples show that a PBS effect can be significant in the absence of
      a significant correlation, and vice versa. In addition to utilizing the PBS model
      in future research, we suggest that this new statistical procedure be used to
      find theoretically important but previously overlooked effects from past studies.

PMID- 30097807
TI  - Adenosine signaling and adenosine deaminase regulation of immune responses:
      impact on the immunopathogenesis of HIV infection.
AB  - Infection by human immunodeficiency virus (HIV) causes the acquired immune
      deficiency syndrome (AIDS), which has devastating effects on the host immune
      system. HIV entry into host cells and subsequent viral replication induce a
      proinflammatory response, hyperactivating immune cells and leading them to death,
      disfunction, and exhaustion. Adenosine is an immunomodulatory molecule that
      suppresses immune cell function to protect tissue integrity. The anti
      inflammatory properties of adenosine modulate the chronic inflammation and immune
      activation caused by HIV. Lack of adenosine contributes to pathogenic events in
      HIV infection. However, immunosuppression by adenosine has its shortcomings, such
      as impairing the immune response, hindering the elimination of the virus and
      control of viral replication. By attempting to control inflammation, adenosine
      feeds a pathogenic cycle affecting immune cells. Deamination of adenosine by ADA
      (adenosine deaminase) counteracts the negative effects of adenosine in immune
      cells, boosting the immune response. This review comprises the connection between
      adenosinergic system and HIV immunopathogenesis, exploring defects in immune cell
      function and the role of ADA in protecting these cells against damage.

PMID- 30097806
TI  - Extrusion 3D Printing of Paracetamol Tablets from a Single Formulation with
      Tunable Release Profiles Through Control of Tablet Geometry.
AB  - An extrusion-based 3D printer was used to fabricate paracetamol tablets with
      different geometries (mesh, ring and solid) from a single paste-based formulation
      formed from standard pharmaceutical ingredients. The tablets demonstrate that
      tunable drug release profiles can be achieved from this single formulation even
      with high drug loading (> 80% w/w). The tablets were evaluated for drug release
      using a USP dissolution testing type I apparatus. The tablets showed well-defined
      release profiles (from immediate to sustained release) controlled by their
      different geometries. The dissolution results showed dependency of drug release
      on the surface area/volume (SA/V) ratio and the SA of the different tablets. The
      tablets with larger SA/V ratios and SA had faster drug release. The 3D printed
      tablets were also evaluated for physical and mechanical properties including
      tablet dimension, drug content, weight variation and breaking force and were
      within acceptable range as defined by the international standards stated in the
      US Pharmacopoeia. X-ray powder diffraction, differential scanning calorimetry and
      attenuated total reflectance Fourier transform infrared spectroscopy were used to
      identify the physical form of the active and to assess possible drug-excipient
      interactions. These data again showed that the tablets meet USP requirement.
      These results clearly demonstrate the potential of 3D printing to create unique
      pharmaceutical manufacturing, and potentially clinical, opportunities. The
      ability to use a single unmodified formulation to achieve defined release
      profiles could allow, for example, relatively straightforward personalization of
      medicines for individuals with different metabolism rates for certain drugs and
      hence could offer significant development and clinical opportunities.

PMID- 30097808
TI  - Porous silicon-poly(epsilon-caprolactone) film composites: evaluation of drug
      release and degradation behavior.
AB  - This work focuses on an evaluation of novel composites of porous silicon (pSi)
      with the biocompatible polymer epsilon-polycaprolactone (PCL) for drug delivery
      and tissue engineering applications. The degradation behavior of the composites
      in terms of their morphology along with the effect of pSi on polymer degradation
      was monitored. PSi particles loaded with the drug camptothecin (CPT) were
      physically embedded into PCL films formed from electrospun PCL fiber sheets.
      PSi/PCL composites revealed a release profile of CPT (monitored via fluorescence
      spectroscopy) in accordance with the Higuchi release model, with significantly
      lower burst release percentage compared to pSi microparticles alone. Degradation
      studies of the composites, using gravimetric analysis, differential scanning
      calorimetry (DSC), and field emission scanning electron microscopy (FESEM),
      carried out in phosphate-buffered saline (PBS) under simulated physiological
      conditions, indicated a modest mass loss (15%) over 5 weeks due to pSi
      dissolution and minor polymer hydrolysis. DSC results showed that, relative to
      PCL-only controls, pSi suppressed crystallization of the polymer film during PBS
      exposure. This suppression affects the evolution of surface morphology during
      this exposure that, in turn, influences the degradation behavior of the polymer.
      The implications of the above properties of these composites as a possible
      therapeutic device are discussed.

PMID- 30097810
TI  - CMTM4 regulates angiogenesis by promoting cell surface recycling of VE-cadherin
      to endothelial adherens junctions.
AB  - Vascular endothelial (VE) cadherin is a key component of endothelial adherens
      junctions (AJs) and plays an important role in maintaining vascular integrity.
      Endocytosis of VE-cadherin regulates junctional strength and a decrease of
      surface VE-cadherin reduces vascular stability. However, disruption of AJs is
      also a requirement for vascular sprouting. Identifying novel regulators of
      endothelial endocytosis could enhance our understanding of angiogenesis. Here, we
      evaluated the angiogenic potential of (CKLF-like MARVEL transmembrane domain 4)
      CMTM4 and assessed in which molecular pathway CMTM4 is involved during
      angiogenesis. Using a 3D vascular assay composed of GFP-labeled HUVECs and dsRED
      labeled pericytes, we demonstrated in vitro that siRNA-mediated CMTM4 silencing
      impairs vascular sprouting. In vivo, CMTM4 silencing by morpholino injection in
      zebrafish larvae inhibits intersomitic vessel growth. Intracellular staining
      revealed that CMTM4 colocalizes with Rab4+ and Rab7+ vesicles, both markers of
      the endocytic trafficking pathway. CMTM4 colocalizes with both membrane-bound and
      internalized VE-cadherin. Adenovirus-mediated CMTM4 overexpression enhances the
      endothelial endocytic pathway, in particular the rapid recycling pathway, shown
      by an increase in early endosomal antigen-1 positive (EEA1+), Rab4+, Rab11+ , and
      Rab7+ vesicles. CMTM4 overexpression enhances membrane-bound VE-cadherin
      internalization, whereas CMTM4 knockdown decreases internalization of VE
      cadherin. CMTM4 overexpression promotes endothelial barrier function, shown by an
      increase in recovery of transendothelial electrical resistance (TEER) after
      thrombin stimulation. We have identified in this study a novel regulatory
      function for CMTM4 in angiogenesis. CMTM4 plays an important role in the turnover
      of membrane-bound VE-cadherin at AJs, mediating endothelial barrier function and
      controlling vascular sprouting.

PMID- 30097811
TI  - Effectiveness of high-intensity interval training on glycemic control and
      cardiorespiratory fitness in patients with type 2 diabetes: a systematic review
      and meta-analysis.
AB  - AIMS: The aim of this systematic review and meta-analysis was to quantify the
      effect of high-intensity interval training (HIIT) on glycemic control and
      cardiorespiratory fitness compared with moderate-intensity training (MICT) and no
      training at all in patients with type 2 diabetes (T2D). METHODS: Relevant
      articles were sourced from PubMed, Embase, the Web of Science, EBSCO, and the
      Cochrane Library. Randomized-controlled trials were included based upon the
      following criteria: participants were clinically diagnosed with T2D, outcomes
      that included glycemic control (e.g., hemoglobin A1c); body composition (e.g.,
      body weight); cardiorespiratory fitness (e.g., VO2peak) are measured at baseline
      and post-intervention and compared with either a MICT or control group. RESULTS:
      Thirteen trials involving 345 patients were finally identified. HIIT elicited a
      significant reduction in BMI, body fat, HbA1c, fasting insulin, and VO2peak in
      patients with type 2 diabetes. Regarding changes in the body composition of
      patients, HIIT showed a great improvement in body weight (mean difference: - 1.22
      kg, 95% confidence interval [CI] - 2.23 to - 0.18, P = 0.02) and body mass index
      (mean difference: - 0.40 kg/m2, 95% CI - 0.78 to - 0.02, P = 0.04) than MICT did.
      Similar results were also found with respect to HbA1c (mean difference: - 0.37,
      95% CI - 0.55 to - 0.19, P < 0.0001); relative VO2peak (mean difference: 3.37
      ml/kg/min, 95% CI 1.88 to 4.87, P < 0.0001); absolute VO2peak (mean difference:
      0.37 L/min, 95% CI 0.28 to 0.45, P < 0.00001). CONCLUSIONS: HIIT may induce more
      positive effects in cardiopulmonary fitness than MICT in T2D patients.

PMID- 30097813
TI  - Fatigue exhaustion of the mitral valve tissue.
AB  - Sudden failure and rupture of the tissue is a rare but serious short-term
      complication after the mitral valve surgical repair. Excessive cyclic loading on
      the suture line of the repair can progressively damage the surrounding tissue and
      finally cause tissue rupture. Moreover, mechanical over-tension, which occurs in
      a diseased mitral valve, gradually leads to tissue floppiness, mitral annular
      dilation, and leaflet rupture. In this work, the rupture mechanics of mitral
      valve is studied by characterizing the fracture toughness exhaustion of healthy
      tissue. Results of this study show that fracture toughness of the posterior
      mitral valve is lower than its anterior counterpart, indicating that posterior
      tissue is more prone to failure. Moreover, the decrease in fracture toughness by
      increasing the number of fatigue cycles shows that excessive mechanical loading
      leads to progressive failure and rupture of mitral valve tissue within a damage
      accumulative process.

PMID- 30097809
TI  - Recent Status of Nanomaterial Fabrication and Their Potential Applications in
      Neurological Disease Management.
AB  - Nanomaterials (NMs) are receiving remarkable attention due to their unique
      properties and structure. They vary from atoms and molecules along with those of
      bulk materials. They can be engineered to act as drug delivery vehicles to cross
      blood-brain barriers (BBBs) and utilized with better efficacy and safety to
      deliver specific molecules into targeted cells as compared to conventional system
      for neurological disorders. Depending on their properties, various metal
      chelators, gold nanoparticles (NPs), micelles, quantum dots, polymeric NPs,
      liposomes, solid lipid NPs, microparticles, carbon nanotubes, and fullerenes have
      been utilized for various purposes including the improvement of drug delivery
      system, treatment response assessment, diagnosis at early stage, and management
      of neurological disorder by using neuro-engineering. BBB regulates micro- and
      macromolecule penetration/movement, thus protecting it from many kinds of
      illness. This phenomenon also prevents drug delivery for the neurological
      disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple
      sclerosis, amyotrophic lateral sclerosis, and primary brain tumors. For some
      neurological disorders (AD and PD), the environmental pollution was considered as
      a major cause, as observed that metal and/or metal oxide from different sources
      are inhaled and get deposited in the lungs/brain. Old age, obesity, diabetes, and
      cardiovascular disease are other factors for rapid deterioration of human health
      and onset of AD. In addition, gene mutations have also been examined to cause the
      early onset familial forms of AD. AD leads to cognitive impairment and plaque
      deposits in the brain leading to neuronal cell death. Based on these facts and
      considerations, this review elucidates the importance of frequently used metal
      chelators, NMs and/or NPs. The present review also discusses the current status
      and future challenges in terms of their application in drug delivery for
      neurological disease management.

PMID- 30097814
TI  - Physiological dynamic compression regulates central energy metabolism in primary
      human chondrocytes.
AB  - Chondrocytes use the pathways of central metabolism to synthesize molecular
      building blocks and energy for cartilage homeostasis. An interesting feature of
      the in vivo chondrocyte environment is the cyclical loading generated in various
      activities (e.g., walking). However, it is unknown whether central metabolism is
      altered by mechanical loading. We hypothesized that physiological dynamic
      compression alters central metabolism in chondrocytes to promote production of
      amino acid precursors for matrix synthesis. We measured the expression of central
      metabolites (e.g., glucose, its derivatives, and relevant co-factors) for primary
      human osteoarthritic chondrocytes in response to 0-30 minutes of compression. To
      analyze the data, we used principal components analysis and ANOVA-simultaneous
      components analysis, as well as metabolic flux analysis. Compression-induced
      metabolic responses consistent with our hypothesis. Additionally, these data show
      that chondrocyte samples from different patient donors exhibit different
      sensitivity to compression. Most importantly, we find that grade IV
      osteoarthritic chondrocytes are capable of synthesizing non-essential amino acids
      and precursors in response to mechanical loading. These results suggest that
      further advances in metabolic engineering of chondrocyte mechanotransduction may
      yield novel translational strategies for cartilage repair.

PMID- 30097812
TI  - Anti-inflammatory Action of Metformin with Respect to CX3CL1/CX3CR1 Signaling in
      Human Placental Circulation in Normal-Glucose Versus High-Glucose Environments.
AB  - Upregulation of chemokine CX3CL1 and its receptor CX3CR1 occurs in the diabetic
      human placenta. Metformin, an insulin-sensitizing biguanide, is used in the
      therapy of diabetic pregnancy. By preventing the activation of NF-kappaB,
      metformin exhibits anti-inflammatory properties. We examined the influence of
      hyperglycemia (25 mmol/L glucose; HG group; N = 36) on metformin-mediated effects
      on CX3CL1 and TNF-alpha production by placental lobules perfused
      extracorporeally. Additionally, CX3CR1 expression and contents of CX3CR1, TNF
      alpha receptor 1 (TNFR1), and NF-kappaB proteins in the placental tissue were
      evaluated. Placentae perfused under normoglycemia (5 mmol/L glucose; NG group; N
      = 36) served as the control. Metformin (2.5 and 5.0 mg/L; subgroups B and C)
      lowered the production of CX3CL1 and TNF-alpha in a dose-dependent and time
      dependent manner. Hyperglycemia did not weaken the strength of these metformin
      effects. Moreover, CX3CL1 levels after perfusion with 5.0 mg/L metformin were
      reduced by 33.28 and 33.83% (at 120 and 150 min, respectively) in the HG-C
      subgroup versus 24.98 and 23.66% in the NG-C subgroup, which indicated an
      augmentation of the metformin action over time in hyperglycemia. CX3CR1
      expression was significantly higher in the HG-B and HG-C subgroups compared to
      that in the NG-B and NG-C subgroups. Increased CX3CR1 protein content in the
      placental lysates was observed in subgroups B and C. The two higher metformin
      concentrations significantly decreased the levels of NF-kappaBp65 protein content
      in both groups. However, the decrease was significantly stronger in
      hyperglycemia. TNFR1 upregulation in the HG group was not affected by metformin.
      Further studies on metformin therapy during pregnancy are needed, including
      safety issues.

PMID- 30097815
TI  - Influences of plaque eccentricity and composition on the stent-plaque-artery
      interaction during stent implantation.
AB  - This work aims to investigate the effects of plaque eccentricity and composition
      on the stent performance and stress distributions of plaque and artery during
      stenting by the finite element method. Three-dimensional stent-plaque-artery
      models for plaques with five different eccentricities and four different
      compositions were simulated, and the influences on stent recoil, stent plastic
      strain, stent foreshortening, stress distributions of artery and plaque, and
      lumen gain were studied. The results show that greater plaque eccentricity leads
      to greater stent recoil, stent plastic strain, stent foreshortening, maximum von
      Mises stresses of artery and plaque, and volume percentage of plaque in higher
      stress. Plaque composition exerts a great effect on all indices except the
      maximum von Mises stress of artery. The lipid pool declines stent recoil, but
      increases the maximum plastic strain of stent due to its softness, while the
      fibrous cap reduces stent foreshortening. Because of the existence of fibrous
      cap/calcified zones, plaque with greater eccentricity and higher mixture of
      components is more vulnerable during stenting process; thus, a larger expanding
      pressure should be carefully applied and a slightly longer stent should be used.
      The present study suggests that the real plaque geometry and composition in
      numerical simulations should be considered as an integral part of stent design
      and development, also is useful in enhancing our understanding of the mechanics
      of stent-plaque-artery interaction during stent implantation to improve the
      stent's long-term clinical outcome.

PMID- 30097817
TI  - Duration Since Never in HIV Care and Immediate Blood-Draw After HIV Diagnosis are
      Associated with Willingness to Link to Care Following Health Department Outreach,
      New York City.
AB  - Late presentation to human immunodeficiency virus (HIV) care is an important
      concern for clinical outcomes and HIV prevention. Significant proportions of HIV
      diagnosed persons are not timely linked to care following HIV diagnosis. We
      implemented and evaluated an intervention to link to care persons never in HIV
      care (NIC). Disease intervention specialists (DIS) traced persons presumed to be
      NIC since HIV diagnosis, offered them assistance with linkage to care, and
      elicited reasons for NIC. We examined the overall outcomes of the intervention
      and reasons for NIC. From January 2013 to December 2016, 121 persons were traced;
      19% were linked to HIV care. Significantly (all P < 0.001) higher proportions of
      persons linked versus not linked to care were diagnosed < 1 year prior to being
      contacted by DIS (48% vs. 13%) or had a HIV-related laboratory test performed
      within 0-7 days of their diagnosis (87% vs. 33%). Among the 105 who provided
      reasons for NIC, most commonly reported were not believing one's HIV diagnosis
      (30%) and lacking medical insurance (18%). Approximately 10% had been to a
      hospital emergency room and 20% to a primary care physician in the past year.
      Health department efforts to link persons NIC for HIV care were effective with a
      minority of eligible persons. Persons diagnosed within 1 year or who underwent
      HIV-related testing within 0-7 days of diagnosis were more likely to link to
      care. Newly HIV-diagnosed persons should be promptly referred to undergo all
      diagnostic testing and assessments on the same day or within 1 week of diagnosis.

PMID- 30097816
TI  - The Role of Nanomaterials and Nanotechnologies in Wastewater Treatment: a
      Bibliometric Analysis.
AB  - Nanomaterials and nanotechnologies (NNs) have been shaping the wastewater
      treatment process unprecedentedly. Bibliometric methods are regarded as an
      indispensable light to guide direction in scientific domain. The present study
      aims to investigate the role of NNs in wastewater treatment with bibliometric
      techniques based on SCI databases from 1997 to 2016. Results showed that China
      (962), USA (324) and Iran (140) are the most productive countries. Chinese
      Academy of Sciences (149), Tongji University (49), and Harbin Institute of
      Technology (40) from China are the most contributive institutions. China and USA
      played central roles in cross-national cooperation, but the top three Chinese
      institutions displayed limited vitality in overseas communication. Rsc Advances
      (108) was the most productive journal followed by Desalination (97) and
      Desalination and Water Treatment (96). The research direction of NNs in
      wastewater treatment was bound up with new NNs. Novel preparation methods and
      nanostructures were powerful impetus for its progress. Nanomaterials like
      graphene, nanotube, magnetic nanoparticle, and silver nanoparticle were hotpots
      in this field. Current and potential application of NNs in wastewater treatment
      as well as challenges were reviewed based on bibliometric results. This study
      also provided researchers future-minded advice about research topic selection.

PMID- 30097818
TI  - Lipids modulate acetic acid and thiol final concentrations in wine during
      fermentation by Saccharomyces cerevisiae * Saccharomyces kudriavzevii hybrids.
AB  - Saccharomyces cerevisiae * Saccharomyces kudriavzevii hybrids are typically used
      for white wine fermentation because of their cryotolerance. One group of these
      hybrids presents a unique ability to release thiol varietal aroma products as
      well as excessive amounts of acetic acid under specific conditions, which is
      detrimental for wine organoleptic quality. The aim of this work is to better
      assess the effects of lipids, sugar concentrations and temperature on the
      production of acetic acid and thiols during wine fermentation. To this end, we
      used a Box-Behnken experimental design and response surface modeling on the
      production of acetic acid and thiols in S. cerevisiae * S. kudriavzevii hybrids
      from the Eg8 family during fermentation of a synthetic must. We showed that these
      hybrids produced lower levels of acetic acid when the initial lipid concentration
      was increased, whereas they produced greater levels when the initial sugar
      concentration was high. Moreover, we found that lipids had a positive impact on
      the final concentrations of 4-methyl-4-mercaptopentan-2-one and 3-mercaptohexan-1
      ol (3MH), giving box tree and citrus flavors, respectively. The increase of 3MH
      was concomitant with a decrease of 3-mercaptohexyl acetate (3MHA) characterized
      by a passion fruit aroma, indicating that lipid addition reduces the rate of 3MH
      acetylation into 3MHA. These results highlight the key role of lipid management
      in acetic acid metabolism and thiol release by S. cerevisiae * S. kudriavzevii
      hybrids and underline its technological interest in alcoholic fermentation to
      avoid the overproduction of volatile acidity while favoring the release of
      volatile thiols.

PMID- 30097819
TI  - Community pharmacists' knowledge and perspectives of reporting adverse drug
      reactions in Australia: a cross-sectional survey.
AB  - : Background Under-reporting of adverse drug reactions (ADRs) by healthcare
      professionals is prevalent worldwide. Community pharmacists are the most
      frequently visited healthcare professional and are well placed to document ADRs
      as a part of their routine practice. Objective To measure community pharmacists'
      knowledge and perspectives towards ADR reporting and their reporting practices.
      Setting Community pharmacists in the New South Wales, Queensland, Victoria and
      Tasmania, Australia. Method A survey tool consisting of 28 items was developed,
      piloted and validated by a panel of expert reviewers. The final anonymised survey
      was distributed online to community pharmacists. Exploratory factor analysis and
      Cronbach's alpha were used to measure the validity and reliability of the tool,
      respectively. Non-parametric statistical tests were used to analyse knowledge,
      perspectives and ADR reporting practices. MAIN OUTCOME MEASURES: Knowledge,
      perceived importance, enablers and barriers to reporting ADRs. Results The survey
      tool showed acceptable validity and reliability. A total of 232 respondents
      completed the survey. The median knowledge score was 5 out of 10 (interquartile
      range, 2). Less than a third of respondents (31.0%) reported sufficient knowledge
      and training on ADR reporting. Only 35.3% of pharmacists reported at least one
      ADR in the previous 12 months. Non-reporting pharmacists were more likely to
      report lack of time as a barrier (P < 0.001), conversely they were more likely to
      report if the practice was remunerated (P = 0.007). Conclusion Under-reporting of
      ADRs by community pharmacists is highly prevalent. Initiatives to educate and
      train them on ADR reporting and simplifying the reporting process may improve
      reporting practices.

PMID- 30097820
TI  - Exploratory analysis for the implementation of antineoplastic logarithmic dose
      banding.
AB  - Background Dose banding (DB) is a strategy to rationalise antineoplastic
      production at Hospital Pharmacy Aseptic Compounding Units (ACUs) and to reduce
      patient's waiting time. DB allows for optimizing workflows and workloads,
      facilitating adoption of new technologies, and increasing safety, quality and
      efficiency of the compounding process. Objective To evaluate the potential impact
      of implementation of Logarithmic DB and to identify antineoplastic agents and
      preparations that fulfil criteria published and establish the number and standard
      doses that could be compounded in advance at the ACU. Setting University and
      Polytechnic third level general hospital. Method Retrospective observational
      study (December 2015-May 2016). Antineoplastic dose production was analysed.
      Investigational drugs were excluded. Three criteria were applied following
      bibliography reviewed to select candidates to be compounded at our ACU as
      standardised using logarithmic DB: (a) Antineoplastic preparations > 250 per
      year; (b) psychochemical stability in optimal storage conditions at least 14
      days; (c) maximum five logarithmic standardised doses that include at least 60%
      of all individualised doses compounded for a given drug. Main outcome measure
      Number of antineoplastic agents, preparations and logarithmic standard doses
      candidates to DB. Results 15,436 antineoplastic individualised doses
      corresponding to 69 antineoplastic agents were analysed. At our institution
      applying selection criteria, 19 (27%) antineoplastic drugs (3 monoclonal
      antibodies, 16 cytotoxic) were potential candidates to DB. 6285 (40%) of
      compounded individualised dose preparations could be prepared in 84 logarithmic
      standard doses in advance. Conclusion Dose banding implementations could
      contribute to rationalise antineoplastic production and increase the ACUs
      compounding capacity.

PMID- 30097823
TI  - 5-Aminolevulinic acid fluorescence guided surgery for recurrent high-grade
      gliomas.
AB  - INTRODUCTION: Fluorescence guided surgery (FGS) with five-aminolevulinic acid (5
      ALA) is expected to revolutionize neurosurgical care of patients with high-grade
      gliomas (HGG). After the recent landmark FDA approval, this optical agent is now
      available to neurosurgeons in the United States. METHODS: This review is designed
      to highlight the evidence for the use of 5-ALA in recurrent HGG surgery for the
      neurosurgical community. The manuscript was prepared in accordance with the
      PRISMA guidelines. RESULTS: Intra-operatively, a strong fluorescent signal is
      highly correlated with the presence of cellular tumor in recurrent HGG, giving it
      a high positive predictive value (PPV). Similar to what is observed in primary
      HGG surgery, false-negative results can occur if tumor cells do not emit
      fluorescence. In addition, false-positive fluorescence signals in tissues devoid
      of tumor cells can be observed more frequently in recurrent HGG compared to the
      primary setting. However, these areas overwhelmingly contain reactive/regressive
      tissue, resection of which is unlikely to cause functional deficits. The safety
      profile of 5-ALA is similarly favorable in primary and recurrent HGG.
      CONCLUSIONS: 5-ALA FGS is a powerful adjunct in the resection of recurrent HGG
      with a high PPV and favorable safety profile. It is therefore the authors'
      opinion to routinely employ this fluorescent agent as a standard of care.

PMID- 30097821
TI  - PubChem chemical structure standardization.
AB  - BACKGROUND: PubChem is a chemical information repository, consisting of three
      primary databases: Substance, Compound, and BioAssay. When individual data
      contributors submit chemical substance descriptions to Substance, the unique
      chemical structures are extracted and stored into Compound through an automated
      process called structure standardization. The present study describes the PubChem
      standardization approaches and analyzes them for their success rates, reasons
      that cause structures to be rejected, and modifications applied to structures
      during the standardization process. Furthermore, the PubChem standardization is
      compared to the structure normalization of the IUPAC International Chemical
      Identifier (InChI) software, as manifested by conversion of the InChI back into a
      chemical structure. RESULTS: The observed rejection rate for substances processed
      by PubChem standardization was 0.36%, which is predominantly attributed to
      structures with invalid atom valences that cannot be readily corrected without
      additional information from contributors. Of all structures that pass
      standardization, 44% are modified in the process, reducing the count of unique
      structures from 53,574,724 in substance to 45,808,881 in compound as identified
      by de-aromatized canonical isomeric SMILES. Even though the processing time is
      very low on average (only 0.4% of structures have individual standardization time
      above 0.1 s), total standardization time is completely dominated by edge cases:
      90% of the time to standardize all structures in PubChem substance is spent on
      the 2.05% of structures with the highest individual standardization time. It is
      worth noting that 60% of the structures obtained from PubChem structure
      standardization are not identical to the chemical structure resulting from the
      InChI (primarily due to preferences for a different tautomeric form).
      CONCLUSIONS: Standardization of chemical structures is complicated by the
      diversity of chemical information and their representations approaches. The
      PubChem standardization is an effective and efficient tool to account for
      molecular diversity and to eliminate invalid/incomplete structures. Further
      development will concentrate on improved tautomer consideration and an expanded
      stereocenter definition. Modifications are difficult to thoroughly validate, with
      slight changes often affecting many thousands of structures and various edge
      cases. The PubChem structure standardization service is accessible as a public
      resource ( https://pubchem.ncbi.nlm.nih.gov/standardize ), and via programmatic
      interfaces.

PMID- 30097822
TI  - Non-invasive genotype prediction of chromosome 1p/19q co-deletion by development
      and validation of an MRI-based radiomics signature in lower-grade gliomas.
AB  - PURPOSE: To perform radiomics analysis for non-invasively predicting chromosome
      1p/19q co-deletion in World Health Organization grade II and III (lower-grade)
      gliomas. METHODS: This retrospective study included 277 patients
      histopathologically diagnosed with lower-grade glioma. Clinical parameters were
      recorded for each patient. We performed a radiomics analysis by extracting 647
      MRI-based features and applied the random forest algorithm to generate a
      radiomics signature for predicting 1p/19q co-deletion in the training cohort (n =
      184). The clinical model consisted of pertinent clinical factors, and was built
      using a logistic regression algorithm. A combined model, incorporating both the
      radiomics signature and related clinical factors, was also constructed. The
      receiver operating characteristics curve was used to evaluate the predictive
      performance. We further validated the predictability of the three developed
      models using a time-independent validation cohort (n = 93). RESULTS: The
      radiomics signature was constructed as an independent predictor for
      differentiating 1p/19q co-deletion genotypes, which demonstrated superior
      performance on both the training and validation cohorts with areas under curve
      (AUCs) of 0.887 and 0.760, respectively. These results outperformed the clinical
      model (AUCs of 0.580 and 0.627 on training and validation cohorts). The AUCs of
      the combined model were 0.885 and 0.753 on training and validation cohorts,
      respectively, which indicated that clinical factors did not present additional
      improvement for the prediction. CONCLUSION: Our study highlighted that an MRI
      based radiomics signature can effectively identify the 1p/19q co-deletion in
      histopathologically diagnosed lower-grade gliomas, thereby offering the potential
      to facilitate non-invasive molecular subtype prediction of gliomas.

PMID- 30097824
TI  - Trametinib for progressive pediatric low-grade gliomas.
AB  - INTRODUCTION: Pediatric pilocytic astrocytomas (PAs) are low grade gliomas and
      the most common brain tumors in children. They often represent a therapeutic
      challenge when incompletely resected as they can recur and progress despite the
      use of several lines of chemotherapeutic agents or even radiation therapy.
      Genetic alterations leading to activation of the mitogen-activated-protein-kinase
      pathway are a hallmark of this disease and offer an interesting therapeutic
      alternative through the use of targeted inhibitors. METHODS: Here, we describe
      six children with sporadic PA who were treated with trametinib, a MEK inhibitor,
      following progression under conventional therapies. Retrospective chart review
      was performed. RESULTS: The median age at diagnosis was 2.3 years (y) old [range
      11 months (m)-8.5 y old]. KIAA1549-BRAF fusion was identified in five cases, and
      hotspot FGFR1/NF1/PTPN11 mutations in one. All patients received at least one
      previous line of chemotherapy (range 1-4). The median time on treatment was 11 m
      (range 4-20). Overall, we observed two partial responses and three minor
      responses as best response; three of these patients are still on therapy.
      Treatment was discontinued in the patient with progressive disease. The most
      frequent toxicities were minor to moderately severe skin rash and gastro
      intestinal symptoms. Two patients had dose reduction due to skin toxicity.
      Quality of life was excellent with decreased hospital visits and a close to
      normal life. CONCLUSION: Trametinib appears to be a suitable option for
      refractory pediatric low-grade glioma and warrants further investigations in case
      of progression.

PMID- 30097826
TI  - A systematic review comparing the diagnostic value of 14-3-3 protein in the
      cerebrospinal fluid, RT-QuIC and RT-QuIC on nasal brushing in sporadic
      Creutzfeldt-Jakob disease.
AB  - BACKGROUND: Sporadic Creutzfeldt-Jakob disease (sCJD) is a human prion disease
      that is a relatively common differential diagnosis in dementia patients.
      Therefore it needs a good diagnostic tool. Brain autopsy is the golden standard
      for the diagnosis of CJD; however, a less invasive technique is 14-3-3 protein
      measurement in the cerebrospinal fluid (CSF). In this systematic review, we
      compared the diagnostic value of the 14-3-3 protein measurement to the newer RT
      QuIC test and a variant of RT-QuIC where nasal brushing is used to collect the
      samples. METHODS: The search via MeSH terms and quality assessment was carried
      out by two individual researchers. RESULTS: In 14-3-3 and RT-QuIC the sensitivity
      was comparable, respectively, 88% and 86%. Specificity however was higher in RT
      QuIC 99.5% compared to 80% in 14-3-3. Nasal brushing showed the best results with
      a sensitivity of 97% and a specificity of 100%. CONCLUSION: Nasal brushing,
      despite being the best diagnostic tool according to the data, needs more study
      since there has only been a few studies regarding the technique. It is safe to
      say that due to the high specificity, RT-QuIC is superior to 14-3-3 testing.

PMID- 30097825
TI  - Impact of adjuvant treatments on survival in Korean patients with WHO grade II
      gliomas: KNOG 15-02 and KROG 16-04 intergroup study.
AB  - INTRODUCTION: Optimal treatment strategies for low-grade glioma (LGG) remain
      controversial. We analyzed treatment outcomes and evaluated prognostic factors of
      adult LGG patients in Korea. METHODS: We reviewed the medical records of 555
      patients diagnosed with WHO grade II LGG (astrocytoma 37.8%, oligoastrocytoma
      15.3%, and oligodendroglioma 46.8%) at 14 institutions between 2000 and 2010.
      Primary and secondary endpoints were progression-free survival (PFS) and overall
      survival (OS). Propensity-score matching (PSM) analyses were performed to correct
      imbalances in patient/tumor characteristics among adjuvant treatment groups.
      RESULTS: The median follow-up time was 83.4 months, and the 5-year PFS and OS
      rates were 52.2% and 83.0%, respectively. Male, older age, poorer performance
      status, multiple lobe involvement, and astrocytoma histology were associated with
      poorer survival. Among the treatment factors, gross total resection (GTR) was
      associated with better PFS and OS, and adjuvant chemotherapy with improved PFS.
      Interestingly, adjuvant radiotherapy (RT) did not improve PFS; rather, it was
      related with poorer OS. Regarding patient/tumor characteristics, the RT group had
      poorer characteristics than the non-RT group. After PSM, we detected a tendency
      for improved PFS in the matched RT group, and no significant difference in OS
      compared with the matched non-RT group. CONCLUSIONS: The achievement of GTR is
      important to improve survival in LGG patients. Adjuvant chemotherapy may enhance
      PFS, but adjuvant RT did not improve survival outcomes. After PSM, we observed
      potential impacts of adjuvant RT on PFS. Our results may reflect real-world
      practice and consequently may help to optimize treatment strategies for LGG.

PMID- 30097827
TI  - Optical coherence tomography retinal ganglion cell complex analysis for the
      detection of early chiasmal compression.
AB  - PURPOSE: To report patients with sellar tumors and chiasmal compression with
      normal visual fields, who demonstrate damage to the retinal nerve fiber layer
      (RNFL) and ganglion cell complex (GCC) on optical coherence tomography (OCT).
      METHODS: Seven patients with sellar tumors causing mass effect on the optic
      chiasm without definite visual field defect, but abnormal GCC are described.
      GCC/RNFL analyses using Cirrus-OCT were classified into centiles based on the
      manufacturer's reference range. RESULTS: In seven patients with radiologic
      compression of the chiasm by a sellar tumor, OCT-GCC thickness detected
      compressive chiasmopathy before visual defects became apparent on standard
      automated visual field testing. Without OCT, our patients would have been
      labelled as having normal visual function and no evidence of compressive
      chiasmopathy. With only OCT-RNFL analysis, 3/7 patients would still have been
      labelled as having no compression of the anterior visual pathways. CONCLUSIONS:
      These patients show that OCT-GCC analysis is more sensitive than visual field
      testing with standard automated perimetry in the detection of compressive
      chiasmopathy or optic neuropathy. These cases and previous studies suggest that
      OCT-GCC analysis may be used in addition to visual field testing to evaluate
      patients with lesions compressing the chiasm.

PMID- 30097828
TI  - Remote Effects of Transplanted Perivascular Adipose Tissue on Endothelial
      Function and Atherosclerosis.
AB  - PURPOSE: Perivascular adipose tissue (PVAT) surrounds the arterial adventitia and
      plays an important role in vascular homeostasis. PVAT expands in obesity, and
      inflamed PVAT can locally promote endothelial dysfunction and atherosclerosis.
      Here, using adipose tissue transplantation, we tested the hypothesis that
      expansion of PVAT can also remotely exacerbate vascular disease. METHODS: Fifty
      milligrams of abdominal aortic PVAT was isolated from high-fat diet (HFD)-fed
      wild-type mice and transplanted onto the abdominal aorta of lean LDL receptor
      knockout mice. Subcutaneous and visceral adipose tissues were used as controls.
      After HFD feeding for 10 weeks, body weight, glucose/insulin sensitivity, and
      lipid levels were measured. Adipocytokine gene expression was assessed in the
      transplanted adipose tissues, and the thoracic aorta was harvested to quantify
      atherosclerotic lesions by Oil-Red O staining and to assess vasorelaxation by
      wire myography. RESULTS: PVAT transplantation did not influence body weight, fat
      composition, lipid levels, or glucose/insulin sensitivity. However, as compared
      with controls, transplantation of PVAT onto the abdominal aorta increased
      thoracic aortic atherosclerosis. Furthermore, PVAT transplantation onto the
      abdominal aorta inhibited endothelium-dependent relaxation in the thoracic aorta.
      MCP-1 and TNF-alpha expression was elevated, while adiponectin expression was
      reduced, in the transplanted PVAT tissue, suggesting augmented inflammation as a
      potential mechanism for the remote vascular effects of transplanted PVAT.
      CONCLUSIONS: These data suggest that PVAT expansion and inflammation in obesity
      can remotely induce endothelial dysfunction and augment atherosclerosis.
      Identifying the underlying mechanisms may lead to novel approaches for risk
      assessment and treatment of obesity-related vascular disease.

PMID- 30097829
TI  - Comparison of esophageal submucosal glands in experimental models for esophagus
      tissue engineering applications.
AB  - OBJECTIVE: Esophagus tissue engineering holds promises to overcome the
      limitations of the presently employed esophageal replacement procedures. This
      study investigated 5 animal models for esophageal submucosal glands (ESMG) to
      identify models appropriate for regenerative medicine applications. Furthermore,
      this study aimed to measure geometric parameters of ESMG that could be utilized
      for fabrication of ESMG-specific scaffolds for esophagus tissue engineering
      applications. METHODS: Ovine, avian, bovine, murine, and porcine esophagus were
      investigated using Hematoxylin-Eosin (HE), Periodic Acid Schiff (PAS), and Alcian
      Blue (AB), with AB applied in 3 pH levels (0.2, 1.0, and 2.5) to detect sulphated
      mucous. Celleye(r) (version F) was employed to gain parametric data on ESMGs
      (size, perimeter, distance to lumen, and acini concentration) necessary for
      scaffold fabrication. RESULTS: Murine, bovine, and ovine esophagus were devoid of
      ESMG. Avian esophagus demonstrated sulphated acid mucous producing ESMGs with a
      holocrine secretion pattern, whereas sulphated acid and neutral mucous producing
      ESMGs with a merocrine secretion pattern were observed in porcine esophagus.
      Distance of ESMGs to lumen ranged from 127-340 MUm (avian) to 916-983 MUm
      (porcine). ESMGs comprised 35% (avian) to 45% (porcine) area of the submucosa.
      ESMG had an area of 125000 MUm2 (avian) to 580000 MUm2 (porcine). CONCLUSION:
      Avian and porcine esophagus possesses ESMGs. However, porcine esophagus
      correlates with data available on human ESMGs. Geometric and parametric data
      obtained from ESMG are valuable for the fabrication of ESMG-specific scaffolds
      for esophagus tissue engineering using the hybrid construct approach.

PMID- 30097830
TI  - Nonfunctional Missense Mutants in Two Well Characterized Cytosolic Enzymes Reveal
      Important Information About Protein Structure and Function.
AB  - The isolation and characterization of 42 unique nonfunctional missense mutants in
      the bacterial cytosolic beta-galactosidase and catechol 2,3-dioxygenase enzymes
      allowed us to examine some of the basic general trends regarding protein
      structure and function. A total of 6 out of the 42, or 14.29% of the missense
      mutants were in alpha-helices, 17 out of the 42, or 40.48%, of the missense
      mutants were in beta-sheets and 19 out of the 42, or 45.24% of the missense
      mutants were in unstructured coil, turn or loop regions. While alpha-helices and
      beta-sheets are undeniably important in protein structure, our results clearly
      indicate that the unstructured regions are just as important. A total of 21 out
      of the 42, or 50.00% of the missense mutants caused either amino acids located on
      the surface of the protein to shift from hydrophilic to hydrophobic or buried
      amino acids to shift from hydrophobic to hydrophilic and resulted in drastic
      changes in hydropathy that would not be preferable. There was generally good
      consensus amongst the widely used algorithms, Chou-Fasman, GOR, Qian-Sejnowski,
      JPred, PSIPRED, Porter and SPIDER, in their ability to predict the presence of
      the secondary structures that were affected by the missense mutants and most of
      the algorithms predicted that the majority of the 42 inactive missense mutants
      would impact the alpha-helical and beta-sheet secondary structures or the
      unstructured coil, turn or loop regions that they altered.

PMID- 30097832
TI  - Acute left ventricular free wall rupture treated by percutaneous intra
      pericardial fibrin-glue infusion.

PMID- 30097831
TI  - Expression and Functional Characterization of Pseudomonas aeruginosa Recombinant
      L.Asparaginase.
AB  - Recombinant l.asparaginase, L.ASNase, from Pseudomonas aeruginosa was purified
      using nickel affinity chromatography. The affinity purified L.ASNase exhibited a
      protein band with a molecular weight of 72.4 kDa on a native polyacrylamide gel
      and 36.276 kDa using SDS-PAGE. The activity of the purified L.ASNase was enhanced
      by Mg2+ and inhibited by Zn2+ at a concentration of 5 mM. The specificity of the
      recombinant L.ASNase towards different substrates was examined, and it was found
      that the enzyme showed the highest activity towards l.asparagine. Moreover, the
      enzyme showed lower activity towards other substrates such as L.glutamine, urea
      and acrylamide. The in vitro hemolysis assay revealed that the purified L.ASNase
      did not show hemolysis effect on blood erythrocytes. Serum and trypsin half-life
      of L.ASNase suggested that the recombinant L.ASNase retained 50% of its initial
      activity after 90 and 60 min incubation period in serum and trypsin separately.

PMID- 30097833
TI  - An unusual case of double-chambered left ventricle : A case of double-chambered
      left ventricle communicated with right ventricle through a ventricular septal
      defect presented during only in diastole and a concomitant mitral valve prolapse.

PMID- 30097834
TI  - The Relationship Between Quality of Life, Psychological Wellbeing, Satisfaction
      with Life and Acculturation of Immigrants in Greece.
AB  - Few studies have examined the quality of life of immigrants in Greece and its
      relations to acculturation. This study explored the quality of life,
      psychological wellbeing and satisfaction with life among Albanian immigrants,
      Pontic Greeks in comparison to native Greeks. Furthermore, the relationship
      between quality of life, psychological wellbeing, satisfaction with life and
      acculturation of Albanian immigrants and Pontic Greeks was investigated. The
      study was based on 520 participants from broader area of Athens, 58.3% (303
      people: 150 men and 153 women) native Greeks, 21.9% (114 people: 57 men and 57
      women) Albanian immigrants and 19.8% (103 people: 50 men and 53 women) Pontic
      Greeks. Quality of life was measured by WHOQOL BREF-while wellbeing was measured
      with Satisfaction With Life Scale and The Affect Balance Scale. An adapted a
      version of Vancouver Index of Acculturation was used to assess acculturation of
      immigrants. The findings indicated three important factors contributed to quality
      of life and wellbeing of immigrants: ethnicity, heritage dimension of
      acculturation and gender. Albanian immigrants and Pontic Greeks scored lower on
      quality of life and satisfaction with life than native Greek.

PMID- 30097836
TI  - High-risk women's risk perception after receiving personalized polygenic breast
      cancer risk information.
AB  - Evidence is accumulating of the clinical utility of single nucleotide
      polymorphisms to effectively stratify risk of breast cancer. Yet for this
      personalized polygenic information to be translated to clinical practice,
      consideration is needed about how this personalized risk information should be
      communicated and the impact on risk perception. This study examined the
      psychosocial implications and the impact on risk perception of communicating
      personalized polygenic breast cancer risk to high-risk women. High-risk women
      with a personal history of breast cancer and an uninformative BRCA1/2 result were
      genotyped in the Variants in Practice study for 22 breast cancer single
      nucleotide polymorphisms. Participants in the highest quartile of polygenic
      breast cancer risk were invited to receive their individual research results. Two
      personalized visual risk communication tools were used to facilitate
      communication of the polygenic information. Participants subsequently undertook a
      semi-structured interview examining their experience of receiving their polygenic
      breast cancer risk and their breast cancer risk perception. Thirty-nine women
      opted to receive their results and were interviewed. The women described the risk
      communication tools as helpful as the tool enabled comparison of their
      personalized breast cancer risk to the general population. Participants
      incorporated the polygenic risk information into their breast cancer risk
      perception, which for some reawakened feelings of being at risk years after an
      uninformative BRCA1/2 result. However, few reported any detrimental emotional
      impact. The delivery of personalized polygenic breast cancer risk to high-risk
      women informed and modified their breast cancer risk perception with little
      emotional impact.

PMID- 30097837
TI  - Introduction: Autonomy in Healthcare.

PMID- 30097835
TI  - Theta-Band Oscillations as an Indicator of Mild Traumatic Brain Injury.
AB  - Mild traumatic brain injury (mTBI) patients continue to pose a diagnostic
      challenge due to their diverse symptoms without trauma-specific changes in
      structural imaging. We addressed here the possible early changes in spontaneous
      oscillatory brain activity after mTBI, and their feasibility as an indicator of
      injury in clinical evaluation. We recorded resting-state magnetoencephalography
      (MEG) data in both eyes-open and eyes-closed conditions from 26 patients (11
      females and 15 males, aged 20-59) with mTBI 6 days-6 months after the injury, and
      compared their spontaneous oscillatory activity to corresponding data from 139
      healthy controls. Twelve of the patients underwent a follow-up measurement at 6
      months. Ten of all patients were without structural lesions in MRI. At single
      subject level, aberrant 4-7 Hz (theta) band activity exceeding the + 2 SD limit
      of the healthy subjects was visible in 7 out of 26 patients; three out of the
      seven patients with abnormal theta activity were without any detectable lesions
      in MRI. Of the patients that participated in the follow-up measurements, five
      showed abnormal theta activity in the first recording, but only two in the second
      measurement. Our results suggest that aberrant theta-band oscillatory activity
      can provide an early objective sign of brain dysfunction after mTBI. In 3/7
      patients, the slow-wave activity was transient and visible only in the first
      recording, urging prompt timing for the measurements in clinical settings.

PMID- 30097838
TI  - Ligand-induced symmetry breaking and concomitant blueshift in the emission
      wavelength of an octahedral chromium complex.
AB  - The resulting distortion of the octahedral symmetry of the complex
      [CrIII(NH3)6]3+ upon replacing the axial ligands with halides (i.e., weaker
      ligands) affects the stability of the doublet state with respect to that of the
      quartet ground state. This substitution affects the doublet-to-quartet transition
      responsible for phosphorescence. The position of the halide with respect to
      ammonia in the spectrochemical series is a major influence on the emission
      wavelength of the complex. The close proximity of fluorine and ammonia in the
      spectrochemical series leads to a blueshift in the emission wavelength when
      fluoride ions are introduced into the complex, thus providing a rational approach
      to the design of blue-phosphorescent materials, which are desirable for OLEDs
      used in full-color displays. Graphical abstract Shifts in the phosphorescence
      emission wavelength of an octahedral Cr(III) complex caused by axial ligand
      substitution. Replacing the axial ligands leads to a change in the relative
      positions of the axial and equatorial ligands in the spectrochemical series,
      which in turn induces a redshift or a blueshift in the emission wavelength.

PMID- 30097840
TI  - Long-term Growth in Congenital Adrenal Hyperplasia.
AB  - OBJECTIVES: To retrospectively assess growth of children with congenital adrenal
      hyperplasia (CAH) with special reference to puberty and to assess longitudinal
      growth and final height of subset of children with CAH. METHODS: A retrospective
      analysis of 30 children (14 boys) with classic CAH (11 salt wasters, 19 simple
      virilisers) followed up for a mean duration of 9.9 +/- 2.4 y (Study period
      December 2002 through December 2016) was performed. Height Z scores, target
      height Z scores, height velocities and laboratory parameters were analysed.
      RESULTS: Children were treated with hydrocortisone in a mean dose of 15.7 +/- 3.3
      mg/m2/d. Mean 17-hydroxy progesterone in boys and girls were 10.8 +/- 6.7 ng/ml
      and 11.3 +/- 9.3 ng/ml respectively. Fifteen children (7 boys) developed central
      precocious puberty at mean age of 7.6 +/- 1.8 y and 13 were treated with GnRH
      analogues for 3.5 y. Of all patients, 18 (10 girls, 8 boys) reached final height
      at a mean age of 14.2 +/- 1.6 y. Mean final height achieved was 158.0 +/- 8.5 cm
      in boys [target height (TH) -165.5 +/- 3.8 cm] and in girls it was 149.9 +/- 6.7
      cm [target height (TH) 154.7 +/- 6.4 cm]. Final height standard deviation scores
      (SDS) for boys and girls were - 2.06 +/- 1.1 (TH-SDS -1.06 +/- 0.5) and - 1.47 +/
      1.1 (TH-SDS -0.56 +/- 1.2) respectively and were not significantly different
      from target height Z scores (p > 0.05). Growth velocity was attenuated during
      pubertal years. CONCLUSIONS: Monitoring growth and puberty in children with CAH
      is critical for optimizing final height.

PMID- 30097839
TI  - The Challenges of the Schooling from Cultural Psychology of Education.
AB  - Education is in the core of societal change in all its different forms-from
      kindergartens to vocational schools and lifelong learning. Education-understood
      as goal-oriented personal movement-re-structures personal lives both inside
      school and outside the school. This special issue stems from the Cultural
      Psychology of Education (Marsico Culture & Psychology, 21(4), 445-454, 2015a, b,
      Journal for the Study of Education and Development, 40(4), 754-781, 2017)-a new
      approach to the field of education that examines how educational experience is
      culturally organized. This special issue is focused on the work of schooling as a
      crucial scientific arena to investigate. It is the follow up of an international
      workshop host by the Centre for Cultural Psychology (at Aalborg University,
      Demark) that was very thought provoking and from where several outcomes came out.
      Some of them are the papers here presented that tried to illuminate the different
      dimensions of the educational context in the East and West society with specific
      attention to the Chinese and Scandinavian educational practices. The dialogue
      between Chinese, European and North American scholars offered a complex view of
      the current educational challenges in the age of globalization. In this paper I
      try to focus on some of the most debated and challenging aspects in educational
      psychology worldwide: diversity, values and practical usability of psychology at
      school. I re-read these "hot topics" with the help of the themes developed by the
      authors of this special issue and in light of Cultural Psychology of Education.
      Then, I conclude by proposing a new agenda for the education of the future.

PMID- 30097841
TI  - Find TB; Screen the Contacts.

PMID- 30097842
TI  - Continuous Distribution of Autistic Traits in an Indian Sample.

PMID- 30097843
TI  - Hypotension After a Pediatric Invasive Procedure: Beware of Takotsubo
      Cardiomyopathy.

PMID- 30097844
TI  - Current Knowledge, Attitude and Practice (KAP) of Pediatricians on Infantile
      Spasms and the Way Forward.

PMID- 30097845
TI  - Treatment of Chronic Hepatitis C Infection with Direct Acting Antivirals in
      Adolescents with Thalassemia Major.
AB  - OBJECTIVES: To assess the efficacy and safety of sofosbuvir based generic Direct
      Acting Antivirals (DAAs) in treatment of Hepatitis C virus (HCV) in adolescents
      with thalassemia major (TM). METHODS: In this prospective single-arm study, 18 TM
      adolescents with Chronic Hepatitis C received sofosbuvir based generic DAAs.
      Patients with genotype 1 and genotype 3 received ledipasvir and daclatasvir
      respectively. Two cirrhotic patients with genotype 3 also received ribavirin.
      RESULTS: The mean age of patients was 15.1 y, of which 12 had genotype 1, 5 had
      genotype 3 and 1 had an undetermined genotype. Six patients had cirrhosis and 1
      was treatment experienced. Sixteen of 18 patients (89%; 95% confidence interval
      74 to 100%) achieved sustained virological response at 3 mo post completion of
      treatment with DAAs. There was a significant reduction in alanine
      aminotransferase levels (p < 0.001), HCV RNA load (p < 0.001) and ferritin levels
      (p < 0.026) at 3 mo post completion of treatment. There were no major adverse
      events associated with the use of DAAs. CONCLUSIONS: Generic DAAs are effective
      and safe in TM adolescents with HCV.

PMID- 30097846
TI  - Role of Automated Urine Flow Cytometry for the Diagnosis of Urinary Tract
      Infection in Children.

PMID- 30097847
TI  - Risks and Benefits of Sodium Polystyrene Sulfonate for Hyperkalemia in Patients
      on Maintenance Hemodialysis.
AB  - BACKGROUND: Concerns about sodium overload when using sodium polystyrene
      sulfonate (Na-resin) as an ion-exchange resin for the treatment of hyperkalemia
      led our institution to gradually shift to the use of calcium polystyrene
      sulfonate (Ca-resin). However, as serum potassium levels were insufficiently
      controlled and patients experienced constipation, we returned to using Na-resin
      and observed better results than previously. OBJECTIVE: As few papers have
      examined the potassium adsorption ability of Ca-resin compared with Na-resin, we
      investigated this issue within our institution. METHODS: We studied potassium
      adsorption in patients who switched from Ca-resin to an equivalent amount of Na
      resin (change group). We also investigated the incidence of sodium loading with
      Na-resin, including in patients newly commencing Na-resin treatment (new start
      group). RESULTS: Mean (+/- standard deviation) serum potassium levels decreased
      significantly, from 5.5 +/- 0.6 to 4.9 +/- 0.6 mEq/l in the change group and from
      5.9 +/- 0.4 to 4.7 +/- 0.6 mEq/l in the new start group. No changes were observed
      in blood pressure, weight gain or serum sodium levels in the change group, but
      serum sodium levels in the new start group increased significantly, from 137.4 +/
      2.3 to 139.0 +/- 2.5 mEq/l, although they remained within the normal range.
      CONCLUSIONS: Our results indicate that Na-resin exhibited an advantage in
      treating hyperkalemia when used in small amounts. However, when prescribing an
      ion-exchange resin at a higher dose, physicians should select the type and amount
      of resin according to the sodium and/or calcium load in each case.

PMID- 30097848
TI  - Pathophysiological Roles of Intracellular Proteases in Neuronal Development and
      Neurological Diseases.
AB  - Proteases are classified into six distinct classes (cysteine, serine, threonine,
      aspartic, glutamic, and metalloproteases) on the basis of catalytic mechanism.
      The cellular control of protein quality senses misfolded or damaged proteins
      principally by selective ubiquitin-proteasome pathway and non-selective autophagy
      lysosome pathway. The two pathways do not only maintain cell homeostasis
      physiologically, but also mediate necrosis and apoptosis pathologically.
      Proteasomes are threonine proteases, whereas cathepsins are lysosomal aspartic
      proteases. Calpains are non-lysosomal cysteine proteases and calcium-dependent
      papain-like enzyme. Calpains and cathepsins are involved in the neuronal
      necrosis, which are accidental cell death. Necrosis is featured by the disruption
      of plasma membranes and lysosomes, the loss of ATP and ribosomes, the lysis of
      cell and nucleus, and the caspase-independent DNA fragmentation. On the other
      hand, caspases are cysteine endoproteases and mediate neuronal cell death such as
      apoptosis and pyroptosis, which are programmed cell death. In the central nervous
      system, necroptosis, ferroptosis and autophagic cell death are also classified
      into programmed cell death. Neuronal apoptosis is characterized by cell
      shrinkage, plasma membrane blebbing, karyorrhexis, chromatin condensation, and
      DNA fragmentation. Necroptosis and pyroptosis are necrotic and lytic forms of
      programmed cell death, respectively. Although autophagy is involved in cell
      survival, it fails to maintain cellular homeostasis, resulting in autophagic cell
      death. Ferroptosis is induced by reactive oxygen species in excitotoxicity of
      glutamate and ischemia-reperfusion. Apoptosis and pyroptosis are dependent on
      caspase-3 and caspase-1, respectively. Autophagic cell death and necroptosis are
      dependent on calpain and cathepsin, respectively, but independent of caspase.
      Although apoptosis has been defined by the absence of morphological features of
      necrosis, the two deaths are both parts of a continuum. The intracellular
      proteases do not only maintain cell homeostasis but also regulate neuronal
      maturation during the development of embryonic brain. Furthermore,
      neurodegenerative diseases are caused by the impairment of quality control
      mechanisms for a proper folding and function of protein.

PMID- 30097849
TI  - Triclocarban Disrupts the Epigenetic Status of Neuronal Cells and Induces AHR/CAR
      Mediated Apoptosis.
AB  - Triclocarban is a phenyl ether that has recently been classified as a contaminant
      of emerging concern. Evidence shows that triclocarban is present in human
      tissues, but little is known about the impact of triclocarban on the nervous
      system, particularly at early developmental stages. This study demonstrated that
      triclocarban that was used at environmentally relevant concentrations induced
      apoptosis in mouse embryonic neurons, inhibited sumoylation, and changed the
      epigenetic status, as evidenced by impaired activities of HDAC, sirtuins, and
      DNMT, global DNA hypomethylation, and alterations of methylation levels of bax,
      bcl2, Ahr, and Car genes. The use of selective antagonists and specific siRNAs,
      which was followed by the co-localization of aryl hydrocarbon receptor (AHR) and
      constitutive androstane receptor (CAR) in mouse neurons, points to the
      involvement of AHR and CAR in triclocarban-induced neurotoxicity. A 24-h
      treatment with triclocarban enhanced protein levels of the receptors which was
      paralleled by Car hypomethylation and Ahr hypermethylation. Car hypomethylation
      is in line with global DNA hypomethylation and explains the increased mRNA and
      protein levels of CAR in response to triclocarban. Ahr hypermethylation could
      reflect reduced Ahr mRNA expression and corresponds to lowered protein levels
      after 3- and 6-h exposures to triclocarban that is likely related to proteasomal
      degradation of activated AHR. We hypothesize that the triclocarban-induced
      apoptosis in mouse neurons and the disruption of epigenetic status involve both
      AHR- and CAR-mediated effects, which may substantiate a fetal basis of the adult
      onset of neurological diseases; however, the expression of the receptors is
      regulated in different ways.

PMID- 30097850
TI  - PRDX6 Inhibits Neurogenesis through Downregulation of WDFY1-Mediated TLR4 Signal.
AB  - Impaired neurogenesis has been associated with several brain disorders, such as
      Alzheimer's disease (AD) and Parkinson's disease (PD). The role of peroxiredoxin
      6 (PRDX6) in neurodegenerative diseases is very controversial. To demonstrate the
      role of PRDX6 in neurogenesis, we compared the neurogenesis ability of PRDX6
      overexpressing transgenic (Tg) mice and wild-type mice and studied the involved
      molecular mechanisms. We showed that the neurogenesis of neural stem cells (NSCs)
      and the expression of the marker protein were lower in PRDX6 Tg-mice than in wild
      type mice. To determine the factors involved in PRDX6-related neural stem cell
      impairment, we performed a microarray experiment. We showed that the expression
      of WDFY1 was dramatically decreased in PRDX6-Tg mice. Moreover, WDFY1 siRNA
      decreases the differentiation ability of primary neural stem cells.
      Interestingly, WDFY1 reportedly recruits the signaling adaptor TIR-domain
      containing adapter-inducing interferon-beta (TRIF) to toll-like receptors (TLRs);
      thus, we showed the relationship among TLRs, PRDX6, and WDFY1. We showed that
      TLR4 was dramatically reduced in PRDX6 Tg mice, and reduced TLR4 expression and
      neurogenesis was reversed by the introduction of WDFY1 plasmid in the neural stem
      cells from PRDX6 Tg mice. This study indicated that PRDX6 inhibits the
      neurogenesis of neural precursor cells through TLR4-dependent downregulation of
      WDFY1 and suggested that the inhibitory effect of PRDX6 on neurogenesis play a
      role in the development of neurodegenerative diseases in the PRDX6 overexpressing
      transgenic mice.

PMID- 30097851
TI  - PET-based myocardial efficiency: Powerful yet under-utilized-now simpler than
      ever.

PMID- 30097852
TI  - Production of single cell oil from cane molasses by Rhodotorula kratochvilovae
      (syn, Rhodosporidium kratochvilovae) SY89 as a biodiesel feedstock.
AB  - BACKGROUND: Single cell oil has long been considered an alternative to
      conventional oil sources. The oil produced can also be used as a feedstock for
      biodiesel production. Oleaginous yeasts have relatively high growth and lipid
      production rates, can utilize a wide variety of cheap agro-industrial wastes such
      as molasses, and can accumulate lipids above 20% of their biomass when they are
      grown in a bioreactor under conditions of controlled excess carbon and nitrogen
      limitation. RESULTS: In this study, Rhodotorula kratochvilovae (syn,
      Rhodosporidium kratochvilovae) SY89 was cultivated in a nitrogen-limited medium
      containing cane molasses as a carbon source. The study aims to provide not only
      information on the production of single cell oil using R. kratochvilovae SY89 on
      cane molasses as a biodiesel feedstock, but also to characterize the biodiesel
      obtained from the resultant lipids. After determination of the sugar content in
      cane molasses, R. kratochvilovae SY89 was grown on the optimized cane molasses
      for 168 h. Under the optimized conditions, the yeast accumulated lipids up to
      38.25 +/- 1.10% on a cellular dry biomass basis. This amount corresponds to a
      lipid yield of 4.82 +/- 0.27 g/L. The fatty acid profiles of the extracted yeast
      lipids were analyzed using gas chromatography, coupled with flame ionization
      detector. A significant amount of oleic acid (58.51 +/- 0.76%), palmitic acid
      (15.70 +/- 1.27%), linoleic acid (13.29 +/- 1.18%) and low amount of other fatty
      acids were detected in the extracted yeast lipids. The lipids were used to
      prepare biodiesel and the yield was 85.30%. The properties of this biodiesel were
      determined and found to be comparable to the specifications established by ASTM
      D6751 and EN14214 related to biodiesel quality. CONCLUSIONS: Based on the results
      obtained, the biodiesel from R. kratochvilovae SY89 oil could be a competitive
      alternative to conventional diesel fuel.

PMID- 30097853
TI  - Potential determinants of physical inactivity among long-term colorectal cancer
      survivors.
AB  - PURPOSE: Since physical activity (PA) has been shown to be associated with better
      prognosis and quality of life (QOL) in colorectal cancer (CRC) patients, this
      study focuses on the barriers of PA among CRC survivors. METHODS: This study is
      based on a population-based study from Germany of 1343 women and men, diagnosed
      with CRC between 2003 and 2008 and being alive five years later. Multivariable
      logistic regression was used to explore associations between baseline as well as
      five-year follow-up (5YFU) characteristics and physical inactivity (PIA) at 5YFU.
      Quartiles were calculated based on metabolic equivalent hours per week of PA at
      baseline and at 5YFU. Participants in quartile 1 were defined as physically
      inactive, and patients in quartile 2 to quartile 4 were defined as physically
      active. RESULTS: Cancer-specific factors such as having a stoma (odds ratio (OR)
      = 1.51, 95% confidence interval (CI) = 1.12-2.04), demographic factors such as
      living in a small town or city (OR = 1.46, 95% CI = 1.05-2.02; OR = 1.42, 95% CI
      = 1.01-2.02), older age (OR = 1.44, 95% CI = 0.80-2.58), or being divorced (OR =
      1.72, 95% CI = 0.96-3.07), as well as lifestyle factors such as being a current
      smoker (OR = 1.54, 95% CI = 1.04-2.29) or being obese (OR = 1.43, 95% CI = 0.96
      2.13) were associated with PIA at 5YFU. Subgroup analyses showed that the
      association between body mass index  and PIA was stronger in women than in men.
      Baseline PA was identified as a strong predictor of PIA at 5YFU. CONCLUSIONS:
      Findings suggest that predominately patients with a stoma, patients living in a
      more populated area, being older, divorced, a current smoker, or obese were more
      likely to be physically inactive and therefore could be targeted to be more
      physically active. IMPLICATIONS FOR CANCER SURVIVORS: Addressing barriers for PA
      might help to develop specific, individually tailored PA interventions to
      overcome PIA and improve the long-term outcome of CRC survivors.

PMID- 30097855
TI  - Candidate susceptibility variants in angioimmunoblastic T-cell lymphoma.
AB  - Angioimmunoblastic T-cell lymphoma (AITL) is a subtype of peripheral T-cell
      lymphoma with a poor prognosis: the 5-year survival rate is approximately 30%.
      Somatic driver mutations have been found in TET2, IDH2, DNMT3A, RHOA, FYN, PLCG1,
      and CD28, whereas germline susceptibility to AITL has to our knowledge not been
      studied. The homogenous Finnish population is well suited for studies on genetic
      predisposition. Here, we performed an exome-wide rare variant analysis in 23 AITL
      patients. No germline mutations were found in the driver genes, implying that
      they are not frequently involved in genetic AITL predisposition. Potentially
      pathogenic variants present in at least two patients and showing significant (p <
      0.01) enrichment in our sample set were found in ten genes: POLK, PRKCB, ZNF676,
      PRRC2B, PCDHGB6, GNL3L, TTC36, OTOG, OSGEPL1, and RASSF9. The most significantly
      enriched variants, causing p.Lys469Ter in a splice variant of POLK and
      p.Pro588His in PRKCB, are intriguing candidates as Polk deficient mice display a
      spontaneous mutator phenotype, whereas PRKCB was recently shown to be somatically
      mutated in 33% of another peripheral T-cell lymphoma, adult T-cell lymphoma. If
      validated, our findings would provide new insight into the pathogenesis of AITL,
      as well as tools for early detection in susceptible individuals.

PMID- 30097857
TI  - Vitamin B3 in Health and Disease: Toward the Second Century of Discovery.
AB  - This introductory chapter briefly reviews the history, chemistry, and
      biochemistry of NAD (the term NAD as it is used here refers to both oxidized and
      reduced forms of the molecule) consuming ADP-ribose transfer enzymes as
      components of the involvement of vitamin B3 in health and disease.

PMID- 30097856
TI  - Selenious-beta-lactoglobulin induces the apoptosis of human lung cancer A549
      cells via an intrinsic mitochondrial pathway.
AB  - In this study, the cytotoxic activity of selenious-beta-lactoglobulin (Se-beta
      Lg) and the anticancer mechanism were investigated in human lung cancer A549
      cells in vitro. MTT assay showed that Se-beta-Lg at 200 MUg/mL exhibited a
      significant suppression effect on A549 cells and the maximum inhibition rate
      reached 90% after 72 h treatment. Flow cytometry analysis revealed that 200
      MUg/mL of Se-beta-Lg induced cell cycle arrest at G0/G1 phase. Cell apoptosis was
      induced via the generation of reactive oxygen species (ROS) and the decrease of
      mitochondrial membrane potential (DeltaPsim) in a time-dependent manner.
      Furthermore, Se-beta-Lg suppressed the expression of Bcl-2 and improved the level
      of Bax, leading to the release of cytochrome c and a higher expression of caspase
      3 in A549 cells. In summary, Se-beta-Lg could induce apoptosis in A549 cells via
      an intrinsic mitochondrial pathway and it might serve as a potential therapeutic
      agent for human lung cancer.

PMID- 30097854
TI  - Comorbid conditions and health-related quality of life in long-term cancer
      survivors-associations with demographic and medical characteristics.
AB  - PURPOSE: Our study provides a detailed overview of comorbid conditions and health
      related quality of life of long-term cancer survivors and analyses the impact of
      demographic, disease- and treatment-related characteristics. METHODS: We present
      data obtained from 1000 survivors across mixed tumour entities 5 and 10 years
      after cancer diagnosis in a cross-sectional study. We analyse the prevalence of
      physical symptoms and health conditions via self-report and health-related
      quality of life using the EORTC QLQ-C30 in comparison to gender- and age-matched
      reference values of the general population. RESULTS: Cancer survivors reported on
      average 5 comorbidities; 23% had 7 or more comorbid conditions. Cancer survivors
      reported higher physical symptom burden than the population-especially fatigue,
      insomnia and pain. Type and prevalence of long-term and late effects differ with
      disease-related factors (e.g. cancer type, treatment) and characteristics of the
      patient. Cancer survivors also reported lower quality of life than the
      population, especially in everyday activities, social life, psychological well
      being and financial difficulties. There was a positive association between high
      quality of life and a low level of morbidity. CONCLUSIONS: The specific knowledge
      about physical long-term consequences for the individual types of cancer could
      raise awareness in health care professionals for high-risk patients and help to
      develop adequate prevention and survivorship-programs. IMPLICATIONS FOR CANCER
      SURVIVORS: Limitations in the mental health area underlines the importance of
      psycho-oncological survivorship-care-plans, which go beyond the time of
      rehabilitation. Special attention should be given to the financial situation of
      patients in long-term follow-up care.

PMID- 30097858
TI  - Monitoring Poly(ADP-Ribosyl)ation in Response to DNA Damage in Live Cells Using
      Fluorescently Tagged Macrodomains.
AB  - Poly(ADP-ribosyl)ation (PARylation) is a dynamic posttranslational modification
      that is added and removed rapidly at sites of DNA damage. PARylation is important
      for numerous aspects of DNA repair including chromatin decondensation and protein
      recruitment. Visualization of PARylation levels after DNA damage induction is
      generally obtained using traditional immunofluorescent techniques on fixed cells,
      which results in limited temporal resolution. Here, we describe a microscopy
      based method to track ADP-ribosylation at break sites. This method relies on DNA
      damage induction using a 405 nm FRAP laser on Hoechst-treated cells expressing
      GFP-tagged PAR-binding proteins, such as macrodomains where the recruitment of
      the PAR-binder to sites of DNA damage gives an indication of PARylation levels.

PMID- 30097859
TI  - In Vitro Techniques for ADP-Ribosylated Substrate Identification.
AB  - ADP-ribosylation is a post-translational modification of proteins that has
      required the development of specific technical approaches for the full definition
      of its physiological roles and regulation. The identification of the enzymes and
      specific substrates of this reaction is an instrumental step toward these aims.
      Here we describe a method for the separation of ADP-ribosylated proteins based on
      the use of the ADP-ribose-binding macro domain of the thermophilic protein
      Af1521, coupled to mass spectrometry analysis for protein identification. This
      method foresees the coupling of the macro domain to resin, an affinity-based pull
      down assay, coupled to a specificity step resulting from the clearing of cell
      lysates with a mutated macro domain unable to bind ADP-ribose. By this method
      both mono- and poly-ADP-ribosylated proteins have been identified.

PMID- 30097861
TI  - Biochemical and Biophysical Assays of PAR-WWE Domain Interactions and Production
      of iso-ADPr for PAR-Binding Analysis.
AB  - The poly(ADP-ribose) polymerase (PARP) family of proteins utilize NAD+ as the
      substrate to modify protein acceptors with either mono(ADP-ribose) (MAR) or
      poly(ADP-ribose) (PAR). MAR and PAR have been shown to regulate distinct cellular
      processes. Iso-ADP-ribose (iso-ADPr) is the smallest internal PAR structural unit
      containing the characteristic ribose-ribose glycosidic bond formed during
      poly(ADP-ribosyl)ation. The WWE domain of RNF146 specifically recognizes the iso
      ADPr moiety in PAR but does not interact with MAR. This provides a way to
      distinguish PAR from MAR modification and to isolate PARylated proteins. Iso-ADPr
      can be used to detect the PAR-specific binding properties of interested proteins.
      Here we describe the detailed method to generate and purify iso-ADPr and its use
      in PAR-binding analysis through isothermal titration calorimetry (ITC) analysis.

PMID- 30097860
TI  - Assessment of Intracellular Auto-Modification Levels of ARTD10 Using Mono-ADP
      Ribose-Specific Macrodomains 2 and 3 of Murine Artd8.
AB  - Mono-ADP-ribosylation is a posttranslational modification, which is catalyzed in
      cells by certain members of the ADP-ribosyltransferase diphtheria toxin-like
      family (ARTD) of ADP-ribosyltransferases (aka PARP enzymes). It involves the
      transfer of a single residue of ADP-ribose (ADPr) from the cofactor NAD+ onto
      substrate proteins. Although 12 of the 17 members of the ARTD family have been
      defined as mono-ARTDs in in vitro assays, relatively little is known about their
      exact cellular functions. A major challenge is the detection of mono-ADP
      ribosylated (MARylated) proteins in cells as no antibodies are available that
      detect exclusively MARylated proteins. As an alternative to classical antibodies,
      the MAR-specific binding domains macro2 and macro3 of Artd8 can be utilized alone
      or in combination, to demonstrate intracellular auto-modification levels of
      ARTD10 in cells in both co-immunoprecipitation and co-localization experiments.
      Here we demonstrate that different macrodomain constructs of human ARTD8 and
      murine Artd8, alone or in combination, exert differences with regard to their
      interaction with ARTD10 in cells. Precisely, while the macrodomains of murine
      Artd8 interacted with ARTD10 in cells in a MARylation-dependent manner, the
      macrodomains of human ARTD8 interacted with ARTD10 independent of its catalytic
      activity. Moreover, we show that a combination of macro2 and macro3 of murine
      Artd8 was recruited more efficiently to ARTD10 during co-localization experiments
      compared to the single domains. Therefore, murine Artd8 macrodomain constructs
      can serve as a tool to evaluate intracellular ARTD10 auto-modification levels
      using the described methods, while the human ARTD8 macrodomains are less suited
      because of ADPr-independent binding to ARTD10. Protocols for co
      immunoprecipitation and co-localization experiments are described in detail.

PMID- 30097862
TI  - Assays for NAD+-Dependent Reactions and NAD+ Metabolites.
AB  - Nicotinamide adenine dinucleotide (NAD+) is an essential redox cofactor and
      signaling molecule that controls the activity of enzymes involved in metabolism,
      DNA repair, and cellular survival, such as the PARPs, CD38, and the sirtuins.
      Here, we describe three methods for measuring the activity of these enzymes: the
      etheno-NAD+ assay measures NAD+ hydrolase activity using an NAD+ analog to
      produce a fluorescent product that is measured in real time; the PNC1 assay
      converts a native product of NAD+ hydrolysis, nicotinamide, into a quantitative
      fluorescent readout; and liquid chromatography tandem mass spectrometry (LC
      MS/MS) is used to characterize the entire NAD+ metabolome in a sample. These
      methods will enable new insights into the roles that NAD+ and the enzymes that
      utilize it play in health and disease.

PMID- 30097863
TI  - Generating Protein-Linked and Protein-Free Mono-, Oligo-, and Poly(ADP-Ribose) In
      Vitro.
AB  - ADP-ribosylation is a covalent posttranslational modification of proteins that is
      catalyzed by various types of ADP-ribosyltransferase (ART) enzymes, including
      members of the poly(ADP-ribose) polymerase (PARP) family. ADP-ribose (ADPR)
      modifications can occur as mono(ADP-ribosyl)ation, oligo(ADP-ribosyl)ation, or
      poly(ADP-ribosyl)ation, depending on the particular ART enzyme catalyzing the
      reaction, as well as the specific reaction conditions. Understanding the biology
      of ADP-ribosylation requires facile and robust means of generating and detecting
      the modification in all of its forms. Here we describe how to generate protein
      linked mono(ADP-ribose), oligo(ADP-ribose), and poly(ADP-ribose) (MAR, OAR, and
      PAR, respectively) in vitro as an automodification of PARPs 1 or 3. First,
      epitope-tagged PARP-1 (a PARP polyenzyme) and PARP-3 (a PARP monoenzyme) are
      expressed individually in insect cells using baculovirus expression vectors, and
      purified using immunoaffinity chromatography. Second, the purified recombinant
      PARPs are incubated individually in the presence of different concentrations of
      NAD+ (as a donor of ADPR groups) and sheared DNA (to activate their catalytic
      activities) resulting in various forms of auto-ADP-ribosylation. Third, the
      products are confirmed using ADPR detection reagents that can distinguish among
      MAR, OAR, and PAR. Finally, if desired, the OAR and PAR can be deproteinized. The
      protein-linked and free MAR, OAR, and PAR generated in these reactions can be
      used as standards, substrates, or binding partners in a variety of ADPR-related
      assays.

PMID- 30097864
TI  - Methods to Study TCDD-Inducible Poly-ADP-Ribose Polymerase (TIPARP) Mono-ADP
      Ribosyltransferase Activity.
AB  - TCDD-inducible poly-ADP-ribose polymerase (TIPARP; also known as PARP7 and
      ARTD14) is a mono-ADP-ribosyltransferase that has emerged as an important
      regulator of innate immunity, stem cell pluripotency, and transcription factor
      regulation. Characterizing TIPARP's catalytic activity and identifying its target
      proteins are critical to understanding its cellular function. Here we describe
      methods that we use to characterize TIPARP catalytic activity and its mono-ADP
      ribosylation of its target proteins.

PMID- 30097865
TI  - Dictyostelium as a Model to Assess Site-Specific ADP-Ribosylation Events.
AB  - The amoeba Dictyostelium discoideum is a single-cell organism that can undergo a
      simple developmental program, making it an excellent model to study the molecular
      mechanisms of cell motility, signal transduction, and cell-type differentiation.
      A variety of human genes that are absent or show limited conservation in other
      invertebrate models have been identified in this organism. This includes ADP
      ribosyltransferases, also known as poly-ADP-ribose polymerases (PARPs), a family
      of proteins that catalyze the addition of single or poly-ADP-ribose moieties onto
      target proteins. The genetic tractability of Dictyostelium and its relatively
      simple genome structure makes it possible to disrupt PARP gene combinations, in
      addition to specific ADP-ribosylation sites at endogenous loci. Together, this
      makes Dictyostelium an attractive model to assess how ADP-ribosylation regulates
      a variety of cellular processes including DNA repair, transcription, and cell
      type specification. Here we describe a range of techniques to study ADP
      ribosylation in Dictyostelium, including analysis of ADP-ribosylation events in
      vitro and in vivo, in addition to approaches to assess the functional roles of
      this modification in vivo.

PMID- 30097866
TI  - Mono-ADP-Ribosylation Catalyzed by Arginine-Specific ADP-Ribosyltransferases.
AB  - Methods are described for determination of arginine-specific mono-ADP
      ribosyltransferase activity of purified proteins and intact cells by monitoring
      the transfer of ADP-ribose from NAD+ to a model substrate, e.g., arginine,
      agmatine, and peptide (human neutrophil peptide-1 [HNP1]), and for the
      nonenzymatic hydrolysis of ADP-ribose-arginine to ornithine, a noncoded amino
      acid. In addition, preparation of purified ADP-ribosylarginine is included as a
      control substrate for ADP-ribosylation reactions.

PMID- 30097867
TI  - Monitoring Expression and Enzyme Activity of Ecto-ARTCs.
AB  - Mammalian ARTCs are expressed as glycosylphosphatidylinositol (GPI)-anchored
      ectoenzymes (ARTC1-ARTC4) or secretory proteins (ARTC5) by different cell types.
      The ARTC2 enzymes catalyze mono-ADP-ribosylation of arginine residues in the
      extracellular domain of membrane proteins or secretory proteins. In this chapter
      we provide protocols to monitor the expression and activity of ARTCs on the cell
      membrane of living cells and in soluble form in biological fluids.

PMID- 30097868
TI  - ADP-Ribosyl-Acceptor Hydrolase Activities Catalyzed by the ARH Family of
      Proteins.
AB  - The ARH family of ADP-ribosyl-acceptor hydrolases is composed of three 39-kDa
      proteins (ARH1, 2, and 3), which hydrolyze specific ADP-ribosylated substrates.
      ARH1 hydrolyzes mono(ADP-ribosyl)ated arginine, which results from actions of
      cholera toxin and other nicotinamide adenine dinucleotide (NAD+):arginine ADP
      ribosyl-transferases, while ARH3 hydrolyzes poly(ADP-ribose) and O-acetyl-ADP
      ribose, resulting from the action of poly(ADP-ribose) polymerases and sirtuins,
      respectively. ARH2 has not been reported to have enzymatic activity, because of
      differences in the catalytic domain. Thus, the substrate specificities of ARH1
      and ARH3 proteins result in unique cellular functions. In this chapter, we
      introduce several methods to monitor the activities of the ARH family members.

PMID- 30097869
TI  - Mono-ADP-Ribosylhydrolase Assays.
AB  - Despite substantial progress in ADP-ribosylation research in recent years, the
      identification of ADP-ribosylated proteins, their ADP-ribose acceptors sites, and
      the respective writers and erasers remains challenging. The use of recently
      developed mass spectrometric methods helps to further characterize the ADP
      ribosylome and its regulatory enzymes under different conditions and in different
      cell types. Validation of these findings may be achieved by in vitro assays for
      the respective enzymes. In the below method, we describe how recombinant ADP
      ribosylated proteins are demodified in vitro with mono-ADP-ribosylhydrolases of
      choice to elucidate substrate and potentially also site specificity of these
      enzymes.

PMID- 30097870
TI  - Hydrolysis of ADP-Ribosylation by Macrodomains.
AB  - ADP-ribosylation is the process of transferring the ADP-ribose moiety from NAD+
      to a substrate. While a number of proteins represent well described substrates
      accepting ADP-ribose modification, a recent report demonstrated biological role
      for DNA ADP-ribosylation as well. The conserved macrodomain fold of several known
      hydrolyses was found to possess de-ADP-ribosylating activity and the ability to
      hydrolyze (reverse) ADP-ribosylation. Here we summarize the methods that can be
      employed to study mono-ADP-ribosylation hydrolysis by macrodomains.

PMID- 30097871
TI  - HPLC-Based Enzyme Assays for Sirtuins.
AB  - Sirtuins are a class of enzymes that utilize nicotinamide adenine dinucleotide,
      NAD+, to remove various acyl groups from protein lysine residues. They have
      important biological functions and regulate numerous biological pathways. Small
      molecules that can modulate sirtuin enzymatic activities are potential
      therapeutic candidates to treat various human diseases. This protocol describes a
      high-performance liquid chromatography (HPLC)-based method to measure the enzyme
      kinetics for SIRT2 and SIRT6's demyristoylase activities and SIRT5's
      desuccinylase activity. This method uses peptide substrates that resemble
      physiological substrates and thus can give more reliable kinetic parameters (K m
      and k cat values) for these enzymes. The data obtained are useful for
      understanding the biological function of sirtuins and developing sirtuin
      modulators.

PMID- 30097872
TI  - Small-Molecule Screening Assay for Mono-ADP-Ribosyltransferases.
AB  - Mono-ADP-ribosyltransferases of the PARP/ARTD enzyme family are enzymes
      catalyzing the transfer of a single ADP-ribose unit to target proteins. The
      enzymes have various roles in vital cellular processes such as DNA repair and
      transcription, and many of the enzymes are linked to cancer-relevant functions.
      Thus inhibition of the enzymes is a potential way to discover and develop new
      drugs against cancer. Here we describe an activity-based screening assay for mono
      ADP-ribosyltransferases. The assay utilizes the natural substrate of the enzymes,
      NAD+, and it is based on chemically converting the leftover substrate to a
      fluorophore and measuring its relative concentration after the enzymatic
      reaction. The assay is homogenous, robust, and cost-effective and, most
      importantly, applicable to mono-ADP-ribosyltransferases as well as poly-ADP
      ribosyltransferases for screening of small-molecule inhibitors against the
      enzymes.

PMID- 30097873
TI  - A Simple, Sensitive, and Generalizable Plate Assay for Screening PARP Inhibitors.
AB  - Poly-ADP-ribose polymerases (also known as ADP-ribosyltransferases or ARTDs) are
      a family of 17 enzymes in humans that catalyze the reversible posttranslational
      modification known as ADP-ribosylation. PARPs are implicated in diverse cellular
      processes, from DNA repair to the unfolded protein response. Small-molecule
      inhibitors of PARPs have improved our understanding of PARP-mediated biology and,
      in some cases, have emerged as promising treatments for cancers and other human
      diseases. However these advancements are hindered, in part, by a poor
      understanding of inhibitor selectivity across the PARP family. Here, we describe
      a simple, sensitive, and generalizable plate assay to test the potency and
      selectivity of small molecules against several PARP enzymes in vitro. In
      principle, this assay can be extended to all active PARPs, providing a convenient
      and direct comparison of inhibitors across the entire PARP enzyme family.

PMID- 30097874
TI  - Nonlocalized Searching of HCD Data for Fast and Sensitive Identification of ADP
      Ribosylated Peptides.
AB  - ADP-ribosylation is a technically challenging PTM which has just emerged into the
      field of PTM-specific proteomics. But this fragile modifier requires special
      treatment on both a data acquisition and data processing level: it is highly
      labile under higher-energy collisional dissociation (HCD), and the degree of
      lability can depend on the site it modifies. Its behavior thus violates some
      assumptions on which proteomics algorithms are based. Here we present
      nonlocalized ADPr searching: a simple principle for maximizing sensitivity toward
      ADP-ribosylation when searching conventional HCD data. By scoring the strong
      fragment ions generally observed in ADPr spectra rather than the weak and often
      absent localization-dependent ions, nonlocalized searches are more sensitive.
      They also run significantly faster, due to reduced search space, and require no
      assumptions about which amino acids can be modified. We illustrate implementation
      in three search systems: Morpheus, MaxQuant, and MASCOT, and we also present a
      means of rapidly finding and extracting ADP-ribosylated peptide spectra from
      large datasets for more focused searching. This approach both improves
      identification of ADP-ribosylated peptides and avoids mis-localization of the
      modification sites.

PMID- 30097875
TI  - Quantitative Determination of MAR Hydrolase Residue Specificity In Vitro by
      Tandem Mass Spectrometry.
AB  - ADP-ribosylation is a posttranslational modification that involves the
      conjugation of monomers and polymers of the small molecule ADP-ribose onto amino
      acid side chains. A family of ADP-ribosyltransferases catalyzes the transfer of
      the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD+) onto a variety
      of amino acid side chains including aspartate, glutamate, lysine, arginine,
      cysteine, and serine. The monomeric form of the modification mono(ADP
      ribosyl)ation (MARylation) is reversed by a number of enzymes including a family
      of MacroD-type macrodomain-containing mono(ADP-ribose) (MAR) hydrolases. Though
      it has been inferred from various chemical tests that these enzymes have
      specificity for MARylated aspartate and glutamate residues in vitro, the amino
      acid and site specificity of different family members are often not unambiguously
      defined. Here we describe a mass spectrometry-based assay to determine the site
      specificity of MAR hydrolases in vitro.

PMID- 30097876
TI  - Detection of ADP-Ribosylating Bacterial Toxins.
AB  - Many bacterial toxins catalyze the transfer of ADP-ribose from nicotinamide
      adenine dinucleotide (NAD) to a host protein. Greater than 35 bacterial ADP
      ribosyltransferase toxins (bARTTs) have been identified. ADP-ribosylation of host
      proteins may be specific or promiscuous. Despite this diversity, bARTTs share a
      common reaction mechanism, three-dimensional active site structure, and a
      conserved active site glutamic acid. Here, we describe how to measure the ADP
      ribosylation of host proteins as purified proteins or within a cell lysate.

PMID- 30097877
TI  - Preparation of Recombinant Alphaviruses for Functional Studies of ADP
      Ribosylation.
AB  - Recently we characterized the mono(ADP-ribosyl) hydrolase (MAR hydrolase)
      activity of the macrodomain of nonstructural protein 3 (nsP3MD) of chikungunya
      virus. Using recombinant viruses with targeted mutations in the macrodomain, we
      demonstrated that hydrolase function is important for viral replication in
      cultured neuronal cells and for neurovirulence in mice. Here, we describe the
      general cell culture and animal model infection protocols for alphaviruses and
      the technical details for biochemical characterization of the MAR hydrolase
      activity of nsP3MD mutants and the preparation of recombinant viruses
      incorporating those mutations through site-directed mutagenesis of an infectious
      cDNA virus clone.

PMID- 30097878
TI  - Monitoring the Sensitivity of T Cell Populations Towards NAD+ Released During
      Cell Preparation.
AB  - Mouse T cells express the toxin-related ecto-ADP-ribosyltransferase ARTC2 that
      catalyzes the posttranslational ADP-ribosylation of cell surface proteins by
      transferring the ADP-ribose group of its substrate nicotinamide adenine
      dinucleotide (NAD+) to arginine residues of its target proteins. One well known
      target of ARTC2 is the ATP-gated P2X7 ion channel. ADP-ribosylation of P2X7
      induces gating of the channel, calcium influx, ecto-domain shedding,
      phosphatidylserine externalization, and finally cell death. Previous studies have
      shown that the ARTC2 substrate NAD+ is released during T cell preparation. Since
      P2X7 is differentially expressed among T cell subpopulations, preparation-related
      ADP-ribosylation has a strong impact on the vitality of T cells that express high
      levels of P2X7. With this chapter we provide a protocol to monitor the
      consequences of preparation-related P2X7 ADP-ribosylation on T cells using
      regulatory T cells as generic T cell subpopulation known to express high levels
      of P2X7. However, this protocol could be easily adapted to other T cell
      populations.

PMID- 30097879
TI  - Identifying Target RNAs of PARPs.
AB  - Posttranscriptional regulation of RNA is an important component of gene
      expression by controlling the total amount of mRNA available for translation into
      protein. It involves multiple pathways including nuclear processing of mRNA and
      its precursors, RNA silencing, and regulation of RNA decay. Poly(ADP-ribose)
      polymerases (PARPs), enzymes that modify target proteins with ADP-ribose, play
      important roles in several RNA-regulatory pathways. RNA-binding PARPs target
      specific transcripts for regulation, and multiple PARPs ADP-ribosylate RNA
      regulatory proteins to alter their localization, activity, or RNA binding.
      Additionally, RNA-binding proteins can bind directly to poly(ADP-ribose) with
      various effects on their function. Here we describe methods to identify and
      confirm specific transcripts that are regulated by PARPs.

PMID- 30097880
TI  - ADPr-Peptide Synthesis.
AB  - Synthetic mono-ADPr-peptides are useful for structural, biochemical, and
      proteomics studies. We describe here a protocol for the preparation of mono-ADPr
      peptides based on a fairly standard Fmoc-based solid-phase synthesis.
      Phosphoribosylated precursor building blocks are introduced into the peptide
      chain on solid-phase and subsequently converted to ADPr-sites by chemical
      phosphorylation with adenosine phosphoramidite. Suitably protected
      phosphoribosylated glutamine, asparagine, and citrulline building blocks
      described in this protocol allow introduction of ADP-Gln, ADPr-Asn, and ADPr-Cit
      into peptide chains as demonstrated for three peptides. Trifunctional amino
      acids, for which base-sensitive side-chain protection is available, can be
      accommodated in the sequences flanking the ADPr-cites.

PMID- 30097881
TI  - Identifying Genomic Sites of ADP-Ribosylation Mediated by Specific Nuclear PARP
      Enzymes Using Click-ChIP.
AB  - Nuclear poly(ADP-ribose) polymerases (PARPs), including PARPs 1, 2, and 3 and the
      Tankyrases, belong to a family of enzymes that can bind to chromatin and
      covalently modify histone- and chromatin-associated proteins with ADP-ribose
      derived from nuclear NAD+. The genomic loci where the nuclear PARPs bind and
      covalently modify chromatin are a fundamental question in PARP biology. Chromatin
      immunoprecipitation coupled with deep sequencing (ChIP-seq) has become an
      essential tool for determining specific sites of binding and modification genome
      wide. Few methods are available, however, for localizing PARP-specific ADP
      ribosylation events across the genome. Here we describe a variation of ChIP-seq,
      called Click-ChIP-seq, for identifying sites of ADP-ribosylation mediated by
      specific PARP family members. This method uses analog-sensitive PARP (asPARP)
      technology, including asPARP mutants and the alkyne-containing "clickable" NAD+
      analog 8-Bu(3-yne)T-NAD+. In this assay, nuclei from cells expressing an asPARP
      protein of interest are incubated with 8-Bu(3-yne)T-NAD+, which is incorporated
      into ADP-ribose modifications mediated only by that specific asPARP protein. The
      nuclei are then subjected to cross-linking with formaldehyde, and the protein
      linked analog ADP-ribose is clicked to biotin using copper-catalyzed alkyne-azide
      "click" chemistry. The chromatin is fragmented, and the fragments containing
      analog ADP-ribose are enriched using streptavidin-mediated precipitation.
      Finally, the enriched DNA is analyzed by qPCR or deep-sequencing experiments to
      determine which genomic loci contain ADP-ribose modifications mediated by the
      specific PARP protein of interest. Click-ChIP-seq has proven to be a robust and
      reproducible method for identifying chromatin-associated, PARP-specific ADP
      ribosylation events genome-wide.

PMID- 30097882
TI  - Methods for Using a Genetically Encoded Fluorescent Biosensor to Monitor Nuclear
      NAD.
AB  - Free nicotinamide adenine dinucleotide (NAD+) serves as substrate for NAD+
      consuming enzymes. As such, the local concentration of free NAD+ can influence
      enzymatic activities. Here we describe methods for using a fluorescent,
      genetically-encoded sensor to measure subcellular NAD+ concentrations. We also
      include a discussion of the limitations and potential applications for the
      current sensor. Presented in this chapter are (1) guidelines for calibrating
      instrumentation and experimental setups using a bead-based method, (2)
      instructions for incorporating required controls and properly performing
      ratiometric measurements in cells, and (3) descriptions of how to evaluate
      relative and quantitative fluctuations using appropriate statistical methods for
      ratio-of-ratio measurements.

PMID- 30097883
TI  - The Barnes Maze Task Reveals Specific Impairment of Spatial Learning Strategy in
      the Intrahippocampal Kainic Acid Model for Temporal Lobe Epilepsy.
AB  - Temporal lobe epilepsy (TLE) is an acquired form of focal epilepsy, in which
      patients not only suffer from unprovoked, devastating seizures, but also from
      severe comorbidities, such as cognitive dysfunction. Correspondingly, several
      animal models of TLE exhibit memory dysfunction, especially spatial memory. The
      Morris water maze test is the most commonly used test for assessing spatial
      learning and memory in rodents. However, high stress and poor swimming abilities
      are common confounders and may contribute to misinterpretation. Particularly
      epileptic mice show altered behaviour during the test as they fail to understand
      the paradigm context. In the Barnes maze test, a dry-land maze test for spatial
      learning and memory that uses milder aversive stimuli, these drawbacks have not
      yet been reported. In the present study, we use this task to evaluate spatial
      learning and memory in the intrahippocampal kainic acid mouse model of TLE. We
      demonstrate that the epileptic mice understand the Barnes maze paradigm context,
      as they learn the location of the escape-chamber by using a serial search
      strategy but fail to develop the more efficient spatial search strategy. Our data
      indicate that the Barnes maze may be a better alternative to the Morris water
      maze for assessing search strategies and impairment of learning and memory in
      epileptic mice.

PMID- 30097884
TI  - Evaluation of the Impacts of Long-Term Enriched Artemia with Bacillus subtilis on
      Growth Performance, Reproduction, Intestinal Microflora, and Resistance to
      Aeromonas hydrophila of Ornamental Fish Poecilia latipinna.
AB  - The present study investigated the effect of enriched Artemia with Bacillus
      subtilis on growth performance, reproductive factors, proximate composition,
      intestinal microflora, and resistance to Aeromonas hydrophila of ornamental fish,
      Poecilia latipinna. Using a completely randomized design, the experiment included
      three groups. The first group was fed with commercial food without any probiotic.
      The second group was fed with unenriched Artemia, and the last group consumed
      long-time enriched Artemia with Bacillus subtilis. The bacteria B. subtilis with
      a density of 1 * 105 CFU mL-1 was added daily to Artemia culture medium. The
      total microflora and Bacillus subtilis counts were significantly increased in
      enriched Artemia compared to the unenriched group (P < 0.05). In fish fed groups,
      growth factors did not show any significant difference (P > 0.05). The maximum
      relative fecundity (28.65 +/- 2.52 egg number g-1), fry production (62.93 +/- 4.6
      individual per female), and fry survival (70.97 +/- 1.56%) obtained in the third
      group were found to be significantly more than those in the first and the second
      groups. Moreover, intestinal bacterial count for Bacillus revealed that the
      higher concentration of bacteria was significantly related to the third group
      (6.24 +/- 0.11 log CFU g-1) (P < 0.05). Maximum protein and fat contents were
      observed in fish fed with Bacillus-enriched Artemia; however, no significant
      difference was found between control and unenriched Artemia groups (P > 0.05).
      The highest amount of ash was observed in fish fed with commercial food without
      any probiotic (P < 0.05). At the end of the feeding period, each of the three
      groups along with positive group (oxytetracycline 100 mg kg-1 of commercial food)
      was exposed to A. hydrophila (BCCM5/LMG3770) bacteria intraperitoneally. Based on
      the results, the lowest cumulative mortality was significantly found in group
      three (68.75 +/- 3.6%) and positive group (62.5 +/- 7.0%) compared to control and
      unenriched Artemia groups (P < 0.05). Hence, B. subtilis with a concentration of
      1 * 105 CFU mL-1 during the period of Artemia culturing can improve the
      reproductive parameters, intestinal microflora, and resistance to pathogenic
      bacteria of Poecilia latipinna.

PMID- 30097886
TI  - Correction to: To See or NOsee: The Debate on the Nocebo Effect and Optimizing
      the Use of Biosimilars.
AB  - The article "To See or NOsee: The Debate on the Nocebo Effect and Optimizing the
      Use of Biosimilars", written by Mourad F. Rezk and Burkhard Pieper was originally
      published electronically on the publisher's internet portal (currently
      SpringerLink) on June 5, 2018 without open access.

PMID- 30097885
TI  - Prostate Cancer in Primary Care.
AB  - Prostate cancer is a common malignancy seen worldwide. The incidence has risen in
      recent decades, mainly fuelled by more widespread use of prostate-specific
      antigen (PSA) testing, although prostate cancer mortality rates have remained
      relatively static over that time period. A man's risk of prostate cancer is
      affected by his age and family history of the disease. Men with prostate cancer
      generally present symptomatically in primary care settings, although some
      diagnoses are made in asymptomatic men undergoing opportunistic PSA screening.
      Symptoms traditionally thought to correlate with prostate cancer include lower
      urinary tract symptoms (LUTS), such as nocturia and poor urinary stream, erectile
      dysfunction and visible haematuria. However, there is significant crossover in
      symptoms between prostate cancer and benign conditions affecting the prostate
      such as benign prostatic hypertrophy (BPH) and prostatitis, making it very
      challenging to distinguish between them on the basis of symptoms. The evidence
      for the performance of PSA in asymptomatic and symptomatic men for the diagnosis
      of prostate cancer is equivocal. PSA is subject to false positive and false
      negative results, affecting its clinical utility as a standalone test. Clinicians
      need to counsel men about the risks and benefits of PSA testing to inform their
      decision-making. Digital rectal examination (DRE) by primary care clinicians has
      some evidence to show discrimination between benign and malignant conditions
      affecting the prostate. Patients referred to secondary care for diagnostic
      testing for prostate cancer will typically undergo a transrectal or transperineal
      biopsy, where a number of samples are taken and sent for histological
      examination. These biopsies are invasive procedures with side effects and a risk
      of infection and sepsis, and alternative tests such as multiparametric magnetic
      resonance imaging (mpMRI) are currently being trialled for their accuracy and
      safety in diagnosing clinically significant prostate cancer.

PMID- 30097887
TI  - Clinical Pharmacokinetics and Pharmacodynamics of Ceftazidime-Avibactam
      Combination: A Model-Informed Strategy for its Clinical Development.
AB  - Avibactam is a non-beta-lactam, beta-lactamase inhibitor of the
      diazabicyclooctane class that covalently acylates its beta-lactamase targets,
      encompassing extended spectrum of activities that cover serine beta-lactamases
      but not metallo-beta-lactamases. Ceftazidime and avibactam have complementary
      pharmacokinetic (PK) profiles. Both drugs have a half-life of approximately 2 h,
      making them suitable to be combined in a fixed-dose combination ratio of 4:1
      (ceftazidime:avibactam). Renal clearance is the primary elimination pathway of
      both ceftazidime and avibactam, and dose adjustment is required in patients with
      moderate and severe renal impairment. Population PK models of ceftazidime and
      avibactam were developed separately and incorporated body weight, disease state,
      ethnicity, and renal function (creatinine clearance) as covariates of clearance
      and volume of distribution. The clinical dosing regimen of ceftazidime/avibactam
      combination was determined from population PK model simulations in the patient
      population for dosing regimens that can achieve sufficient joint probability of
      target attainment for ceftazidime minimum inhibitory concentration (MIC) of 8
      mg/L at a fixed 4 mg/L avibactam concentration (MIC <= 8/4 mg/L); 8 mg/L is the
      breakpoint of ceftazidime in Enterobacteriaceae and Pseudomonas aeruginosa for
      the target pharmacodynamic indices of ceftazidime and avibactam of 50% time at
      which the free ceftazidime concentration is above the MIC (fT > MIC) and 50% time
      at which the free avibactam is above a threshold concentration of 1 mg/L (fT >
      CT). Whereas the static index approach does not take into account the changing
      potency of ceftazidime in the presence of changing avibactam concentration, a
      mathematical model based on kill-curve kinetics was utilized to validate the dose
      selection in humans. The clinical dosing regimen of 2/0.5 g ceftazidime/avibactam
      administered every 8 h as a 2-h intravenous infusion in patients with normal
      renal function, with dose adjustment in renal impairment, demonstrated
      statistical non-inferiority to carbapenem in phase III studies on the treatment
      of complicated intra-abdominal infection, complicated urinary tract infection,
      and nosocomial pneumonia, including ceftazidime non-susceptible Gram-negative
      pathogens. The success of the phase III studies validated the dose selection and
      exposure target that were associated with efficacy based on a model-informed
      approach.

PMID- 30097889
TI  - Do Long-time Team-mates Lead to Better Team Performance? A Social Network
      Analysis of Data from Major League Baseball.
AB  - OBJECTIVES: To estimate the effects of team-mate shared experience on overall
      team performance as well as to determine whether concentration of time together
      among subgroups of players and/or focal players enhances team performance.
      METHODS: Social network analysis (SNA) was used to model 30 active Major League
      Baseball teams from 2006 to 2015 with years of experience together connecting
      players resulting in 300 individual team networks. Social network metrics of
      network density, network centralization, and average weighted degree were
      computed and analyzed with team attributes by generalized least squares
      regression to predict wins, and team rank. Logistic regression was used to
      predict binary outcomes of world series and division wins. RESULTS: Network
      density was negatively associated with team rank (beta = - 0.115, p = .05), while
      average weighted degree was positively associated with team rank (beta = 0.147, p
      = .01). On average, each extra year of shared player time per team was associated
      with 14.86% higher probability of winning a division title (B = 2.69, exp(B) =
      14.86, p = .05). Each extra shared year of infield membership among team-mates
      predicted 2.4% lower odds of winning the world series (B = -0.024, exp(B) =
      0.976, p = .01), and each extra shared year between outfield players predicted
      2.9% lower probability of winning a team's division (B = -0.029. exp(B) = 0.972,
      p = .05). CONCLUSIONS: Prolonged shared time between players is beneficial when
      it is spread evenly among all players of the team, whereas having few focal
      players who have been on a team together for many years is a disadvantage to
      overall performance.

PMID- 30097890
TI  - On the use of digital technologies to reduce the public health impacts of
      cannabis legalization in Canada.
AB  - The imminent legalization of recreational cannabis represents a considerable
      public health challenge that requires proactive measures to ensure a responsible
      transition. The federal government recognizes the need for strict regulation to
      reduce cannabis-related health harms, notably among the youth. Additionally, the
      government plans to oversee a national public awareness campaign as part of a
      harm-reduction strategy. In light of the public health risks of cannabis
      legalization, this paper proposes the implementation of increasingly popular,
      evidence-based, preventive, and therapeutic digital interventions to minimize the
      harms of this policy among adolescents and young adults. These E-health
      interventions facilitate healthcare delivery, improve patient care, and overcome
      stigmatization, especially in the context of substance abuse. Therefore, we argue
      that a continuum of digital tools, including prevention programs, educational
      material, and therapeutic interventions aimed at reducing risky consumption of
      cannabis, should be embraced as part of a comprehensive public health strategy by
      the federal government in anticipation of legalization later this year.

PMID- 30097888
TI  - Metastatic Melanoma: Recent Therapeutic Progress and Future Perspectives.
AB  - The prognosis of patients with metastatic melanoma has dramatically improved in
      recent years with the introduction of two new therapeutic strategies. BRAF and
      MEK inhibitors are small molecules that are able to block the mitogen-activated
      protein kinase (MAPK) pathway, which is constitutively activated by recurrent
      BRAF V600 mutations in 45% of melanoma patients. These agents were shown to
      provide a rapid and strong response but are often limited by a high rate of
      secondary resistance. Monoclonal antibodies against the immune checkpoints
      cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD
      1) can restore an efficient and durable anti-tumor immunity, even following
      treatment discontinuation. Anti-PD-1 antibodies were shown to prolong survival of
      metastatic melanoma patients and a real cure seems to be obtainable in some
      patients. Many more therapies are currently under investigation, given that 50%
      of patients still do not have long-term benefits from approved treatments. The
      main goal is to avoid or circumvent primary or secondary immune resistance to
      anti-PD-1 therapy not only by targeting other players in the tumor
      microenvironment but also by optimizing treatment sequencing and combining anti
      PD-1 with other treatments, especially with BRAF and MEK inhibitors. The
      unexpected major successes of immunotherapies in melanoma have opened the way for
      the development of these treatments in other cancers. In this review, we describe
      the different available treatments, their toxicities, and the key components of
      our decisional algorithms, and give an overview of what we expect to be the near
      future of melanoma treatment.

PMID- 30097891
TI  - Embedding health equity strategically within built environments.
AB  - BACKGROUND: Population health approaches are visible among multidisciplinary
      methods used in urban design and planning, but attention to health equity is not
      always an explicit focus. Population and Public Health-Saskatoon Health Region
      recognized the need for frameworks to prioritize, integrate and measure health
      equity within local built environments. SETTING: A cross-department healthy built
      environment (HBE) initiative coordinated activities involving Health Promotion,
      Environmental Public Health, Public Health Observatory, and Medical Health
      Officers engaged with municipal, academic and community partners in Saskatoon,
      Saskatchewan. INTERVENTIONS: The HBE team conducted evidence reviews and
      consulted with partners to identify common health equity issues in built
      environments and best and leading practices to address them. The HBE team then
      prioritized and undertook projects to model a health equity approach. OUTCOMES:
      Projects included the following: (1) developing a Health Equity in Healthy Built
      Environment Framework; (2) engaging in a partner campaign highlighting built
      environment and health equity during a municipal election; (3) producing a Health
      Equity Impact Assessment (HEIA) report on the City of Saskatoon's growth plan;
      and (4) developing a monitoring and evaluation framework for health equity
      outcomes. Other outputs include making new connections between local HBE and
      poverty reduction efforts and promoting social inclusion guidelines in
      consultation processes. IMPLICATIONS: Within a population health approach to HBE,
      an explicit focus on health equity can be a catalyst for engaging partners in
      cross-sectoral action for building inclusive physical and social environments.

PMID- 30097892
TI  - The Runs: Sudden Copious Ostomy Output in an Acolonic Hirschsprung Disease
      Patient with Short Gut Syndrome.

PMID- 30097893
TI  - Medical Prophylaxis of Post-Surgical Crohn's Disease Recurrence: Towards Timely
      Anti-TNF Therapy.

PMID- 30097895
TI  - Characterization of clarithromycin heteroresistance among Helicobacter pylori
      strains isolated from the antrum and corpus of the stomach.
AB  - Mixed infections and heteroresistance of Helicobacter pylori contribute to
      decreased efficacy of treatments. This study aimed to investigate frequency of
      clarithromycin heteroresistance and its link with mixed infections, medication
      history, and disease severity. A total of 40 pairs of H. pylori strains were
      isolated from the antrum and corpus of 97 patients. Susceptibility of the strains
      to clarithromycin was measured by agar dilution method. Site-specific mutations
      of 23S rRNA at A2143G, A2142G, and A2142C positions were analyzed by PCR and
      genomic relatedness of pairs of the strains was determined by random amplified
      polymorphic DNA (RAPD)-PCR. The results showed a prevalence of 35% (14/40)
      clarithromycin resistance. Diversity of the antrum and corpus isolates in
      resistance to clarithromycin was detected among 17.5% (7/40) of the patients.
      Similarly, diversity in MIC value was also detected in two patients infected with
      the sensitive strains. Significant difference in frequency of resistance was
      detected among patients with peptic ulcer disease (PUD) (MIC90 32 MUg/mL) and
      severe gastritis (MIC90 16 MUg/mL), compared with those who suffered from non
      ulcer dyspepsia (NUD) (MIC90 8 MUg/mL) and chronic gastritis (MIC90 0.25 MUg/mL).
      MIC values showed 8-32 folds increased levels in the corpus. A2142G, A2143G, and
      A2142C mutations were detected in three, two, and two patients, respectively, but
      not observed in 46% of the resistant strains. RAPD-PCR fingerprints showed
      identical molecular patterns for the isolates of the corpus and antrum in each
      patient. In conclusion, microevolution of H. pylori strains during chronic
      infection, rather than mixed infection, and inappropriate medication appear to be
      main reasons of treatment failure in adults.

PMID- 30097894
TI  - IL-17A Promotes Initiation and Development of Intestinal Fibrosis Through EMT.
AB  - BACKGROUND: Intestinal fibrosis is a common complication of Crohn's disease (CD).
      Its exact mechanism is still unclear, and effective treatments to control or
      reverse the fibrosis process are unavailable. Epithelial-mesenchymal transition
      (EMT) may promote intestinal fibrosis by increasing deposition of extracellular
      matrix protein. IL-17A is a pro-inflammatory cytokine, and it has been shown as a
      profibrotic factor as its association with fibrosis of multiple organs was
      reported. AIMS: To assess the roles of IL-17A and EMT in the initiation and
      development of intestinal fibrosis and to verify the potential inductive effect
      of IL-17A on EMT. METHODS: In this study, we evaluated the expression of IL-17A
      and EMT-related genes in colonic mucosal biopsy tissues of CD patients and
      control individuals. Then, we examined the changes of EMT-related genes and
      fibrosis-related genes of IEC-6 cells which cultured for 72 h under increasing
      concentrations of IL-17A or with TGF-beta1, to verify the potential inductive
      effect of IL-17A on EMT in vitro. We blocked the IL-17A of the mouse model of
      TNBS-induced experimental intestinal colitis and fibrosis to further verify the
      potential inductive effect of IL-17A on EMT in vivo. RESULTS: We found the
      occurrence of EMT and high-level expression of IL-17A in intestinal mucosa of CD
      patients. Using IEC-6 cells, we showed that IL-17A may induce EMT in intestinal
      epithelial cells that come with reduced E-cadherin expression and increased
      expression of vimentin, snail, and alpha-SMA. We further found that anti-IL-17A
      treatment alleviated intestinal fibrosis through reducing EMT in mouse intestine.
      CONCLUSIONS: Our study confirmed the involvement of IL-17A in the development of
      intestinal fibrosis through inducing EMT.

PMID- 30097896
TI  - Recommendations for the management of rheumatoid arthritis in the Eastern
      Mediterranean region: an adolopment of the 2015 American College of Rheumatology
      guidelines.
AB  - Clinical practice guidelines can assist rheumatologists in the proper
      prescription of newer treatment for rheumatoid arthritis (RA). The objective of
      this paper is to report on the recommendations for the management of patients
      with RA in the Eastern Mediterranean region. We adapted the 2015 American College
      of Rheumatology guidelines in two separate waves. We used the adolopment
      methodology, and followed the 18 steps of the "Guidelines 2.0" comprehensive
      checklist for guideline development. For each question, we updated the original
      guidelines' evidence synthesis, and we developed an Evidence Profile (EP) and an
      Evidence to Decision (EtD) table. In the first wave, we adoloped eight out of the
      15 original questions on early RA. The strength changed for five of these
      recommendations from strong to conditional, due to one or more of the following
      factors: cost, impact on health equities, the balance of benefits, and harms and
      acceptability. In the second wave, we adoloped eight out of the original 44
      questions on established RA. The strength changed for two of these
      recommendations from strong to conditional, in both cases due to cost, impact on
      health equities, balance of benefits and harms, and acceptability. The panel also
      developed a good practice recommendation. We successfully adoloped 16
      recommendations for the management of early and established RA in the Eastern
      Mediterranean region. The process proved feasible and sensitive to contextual
      factors.

PMID- 30097899
TI  - A Rapid and Cost-Effective Device for Testing Minimal Erythema Dose.
AB  - INTRODUCTION: We describe a novel device for rapid and economical minimal
      erythema dose testing in patients undergoing ultraviolet (UV) light phototherapy
      for treatment of skin diseases. METHODS: A minimal erythema testing device was
      designed and created using transparent plastic sheeting and printed patterns with
      increasing ink density, allowing for graded UV transmission of 100%, 80%, 60%,
      40%, 20%, and 10% energy through six 10-mm square apertures. The plastic sheet
      was placed in a UV-impenetrable and Velcro-fitted adjustable sleeve, designed to
      fit easily onto a patient's arm. A pilot validation study was performed,
      comparing this device with a commercially available windowed device in which the
      dose is controlled by varying the UV exposure time through sequential opening of
      each window. The pilot was conducted on healthy skin of two human subjects with
      different Fitzpatrick skin types. RESULTS: In our subjects, tested with one
      device on each forearm, the minimal erythema dose (MED), judged visually, was
      identical. However, the test device allowed MED testing in 3 min compared with 15
      min for the traditional device. The test device is equally effective for use with
      ultraviolet-A (UVA), narrowband ultraviolet-B (NB-UVB) and broadband ultraviolet
      B (BB-UVB) wavelengths. The test device is economical, with manufacturing cost of
      less than US $2. CONCLUSION: We designed an MED testing device that is quick,
      accurate, cost-effective, and easy to use in the setting of a busy phototherapy
      practice. This device therefore has many advantages over existing MED testing
      approaches.

PMID- 30097898
TI  - Cholecystectomy in Patients Submitted to Bariatric Procedure: A Systematic Review
      and Meta-analysis.
AB  - Weight loss following bariatric surgery increases risk for biliary stones. This
      study performed a meta-analysis evaluating cholecystectomy risks in bariatric
      patients. A systematic review and meta-analysis were performed. We evaluated the
      incidence rate for biliary complications in patients followed after bariatric
      surgery. We compared the risks for mortality, complications, and in hospital stay
      among patient submitted to cholecystectomy before, concomitantly with or after
      bariatric surgery, as well as patients submitted to bariatric surgery and
      cholecystectomy, and patients submitted only to bariatric surgery in order to
      evaluate when to perform cholecystectomy in morbidly obese patients. The
      incidence rate of biliary complications was 5.54 cases/1000 patient year. The
      addition of cholecystectomy to bariatric surgery resulted in an increased risk
      for complications (RD = 0.02). The risk for complications (RD = - 0.09) and
      reoperation (RD = - 0.02) was lower when performed concomitantly with bariatric
      surgery compared to post-bariatric procedure. Prophylactic cholecystectomy may be
      avoided. Patients submitted to bariatric surgery have low incidence rate of
      biliary complications, and concomitant cholecystectomy increases the risk for
      postoperative complications and operative time. If cholecystectomy is not
      indicated, patients should be carefully followed with attention for biliary
      complications, once cholecystectomy performed post-bariatric surgery is at higher
      risk for complications and reoperations.

PMID- 30097897
TI  - Safety of Blood Glucose Response Following Exercise Training After Bariatric
      Surgery.
AB  - INTRODUCTION: Safety of exercise training in relationship with the risk of
      hypoglycemia post-bariatric surgery is unknown. OBJECTIVE: To evaluate the safety
      and magnitude of changes in blood glucose levels during exercise training
      following bariatric surgery. MATERIAL AND METHODS: Twenty-nine severely obese
      patients undergoing either sleeve gastrectomy (SG) (n = 16) or biliopancreatic
      diversion with duodenal switch (BPD-DS) (n = 13) were prospectively enrolled.
      Three months after surgery, patients participated in a 12-week supervised
      exercise training program, (35-min aerobic training with a 25-min resistance
      exercises) three times a week. Capillary blood glucose (CBG) levels were measured
      immediately before and after each exercise session. RESULTS: Seven patients (24%)
      had type 2 diabetes before surgery (mean duration: 10 years); four patients still
      have type 2 diabetes 3 months post-bariatric surgery. A total of 577 exercise
      training sessions with CBG monitoring were recorded. Only seven sessions (1.2%)
      were associated with an episode of asymptomatic hypoglycemia (CBG <= 3.9 mmol/L).
      Patients with type 2 diabetes at baseline showed a larger decrease in CBG with
      pre-exercise CBG being between 6.1 and 8.0 mmol/L (- 1.6 +/- 1.2 vs. - 1.1 +/-
      0.9 mmol/L, p = 0.02). BPD-DS patients with CBG >= 6.1 mmol/L showed higher
      reduction in CBG following exercise vs. SG patients (- 1.7 +/- 1.0 vs. - 1.1 +/-
      1.1 mmol/L; p < 0.001 and - 4.3 +/- 1.0 vs. - 2.2 +/- 1.4 mmol/L, p < 0.001,
      respectively). CONCLUSION: Three months after bariatric surgery, exercise
      training program in patients without and with type 2 diabetes is safe, and is
      associated with a desirable glycemic profile, with few episodes of asymptomatic
      hypoglycemia.

PMID- 30097900
TI  - The secretory phenotype of senescent astrocytes isolated from Wistar newborn rats
      changes with anti-inflammatory drugs, but does not have a short-term effect on
      neuronal mitochondrial potential.
AB  - In the central nervous system (CNS), senescent astrocytes have been associated
      with neurodegeneration. Senescent cells secrete a complex mixture of pro
      inflammatory factors, which are collectively called Senescence Associated
      Secretory Phenotype (SASP). The SASP components can vary depending on the cell
      type, senescence inducer and time. The SASP has been mainly studied in
      fibroblasts and epithelial cells, but little is known in the context of the CNS.
      Here, the SASP profile in senescent astrocytes isolated from Wistar newborn rats
      induced to senescence by oxidative stress or by proteasome inhibition was
      analyzed. Senescent astrocytes secreted predominantly chemokines and IL-1alpha,
      but no IL-6. The effect of the anti-inflammatory drugs, sulforaphane (SFN) and
      dehydroepiandrosterone (DHEA), on the SASP profile was evaluated. Our results
      showed that SFN and DHEA decreased IL-1alpha secretion while increasing IL-10,
      thus modifying the SASP to a less anti-inflammatory profile. Primary neurons were
      subjected to the conditioned media obtained from drug-treated senescent
      astrocytes, and their mitochondrial membrane potential was evaluated.

PMID- 30097901
TI  - Ultrasound morphology of cecal appendix in pet rabbits.
AB  - PURPOSE: Cecal appendix is the terminal part of cecum and is characteristic of
      rabbit, among domestic animals. The purpose of this work is to evaluate its
      morphology upon ultrasound. METHODS: A prospective study was planned for the
      duration of approximately 1 year. Rabbits presented in the study period for
      abdominal ultrasound with no clinically evident alterations of the
      gastrointestinal tract were eligible for inclusion in the study. Abdominal
      ultrasound was performed under manual restrain with a high frequency linear probe
      (8-18 MHz). RESULTS: Cecal appendix was visualized in 40/42 rabbits (95.2%) with
      median or left paramedian views. The wall appeared multilayered in accordance
      with normal bowel anatomy, and the luminal content showed in all cases an
      alimentary pattern. Measurement of appendix wall thickness (AWT) was possible in
      all 40 rabbits in which the appendix was visualized while measurement of the
      appendix diameter (AD) was possible in 39 rabbits. Reference intervals for AWT
      were 1.1-2.1 mm, and for AD were 3.9-8.8 mm. There was a negative correlation
      between age and AWT (r = - 0.35, P = 0.027) and a moderate positive correlation
      between AWT and AD (r = 0.71, P < 0.001). CONCLUSIONS: Cecal appendix is
      recognizable via ultrasound in the vast majority of rabbits. We describe the
      normal morphological aspect of the appendix and we provide reference intervals
      for wall thickness and diameter of the appendix, in order to aid in the diagnosis
      of disorders of the appendix. The negative correlation between age and AWT
      indicates lower values of AWT associated with increasing age that could represent
      the physiological decrease in the immunitary function of the appendix in aged
      rabbits.

PMID- 30097902
TI  - Short-term efficacy of high intensity group and individual education in patients
      with type 2 diabetes: a randomized single-center trial.
AB  - PURPOSE: The aim of this randomized study was to examine the efficacy of two high
      intensity educational programs: the conversation maps-based (CMTM) education and
      the individual education (IE), compared to usual care (UC) in a cohort of type 2
      diabetic (T2DM) patients. METHODS: Ninety T2DM outpatients (30 per group) were
      randomized and 79 finished the study and were analyzed. The CMTM and IE groups
      received four educational sessions at 0, 4, 8 and 12 weeks, while the UC group
      received two brief individual sessions at 0 and 12 weeks. We evaluated glycemic
      control (HbA1c), diabetes treatment, body mass index (BMI) and carried out a
      questionnaire survey at three time points (before intervention, at 12 and at 32
      weeks) to assess patients' satisfaction, attitudes toward diabetes and dietary
      knowledge. RESULTS: All the three groups showed a significant and comparable
      reduction of both HbA1c and BMI. Diabetes therapy needed to be reinforced in a
      higher percentage of cases (39.3%) among UC patients compared to the IE (14.8%; p
      = 0.04) and the CMTM (8.3%; p = 0.01) groups. At 32 weeks Diabetes Treatment
      Satisfaction (DTSQ Q1 + Q4-8) significantly improved in the CMTM group (25.8 +/-
      4.5 vs. 22.4 +/- 6.0; p < 0.01) and attitudes toward diabetes (ATT19)
      significantly improved in the IE group (58.0 +/- 4.7 vs. 55.3 +/- 5.1; p = 0.02).
      CONCLUSIONS: Our trial provides preliminary data regarding the efficacy of
      structured group and individual education on achieving better glyco-metabolic
      control without drug therapy reinforcement and with positive effects on patients'
      attitude and treatment satisfaction.

PMID- 30097904
TI  - Positive and Negative Affect Change among People Living with HIV: a One-Year
      Prospective Study.
AB  - PURPOSE: The aim of this study was to investigate the heterogeneity of changes in
      affective states, i.e., positive (PA) and negative (NA) affect, as well as the
      sociodemographic and clinical covariates of these changes among people living
      with HIV (PLWH) in a 1-year prospective study. METHOD: Participants were 141
      ambulatory patients (15% female) with a confirmed diagnosis of HIV infection who
      were undergoing antiretroviral treatment. Their affective states were assessed
      three times, with 6-month intervals, using the positive and negative general
      affect scale (PANAS-X). Sociodemographic (gender, age, relationship status,
      education, employment) and clinical variables (CD4 count assessed via self
      report, HIV/AIDS status, time since HIV diagnosis and antiretroviral treatment
      duration) were also obtained. RESULTS: Heterogeneity of changes was present only
      for NA, whereas PA decreased gradually in the whole sample. Time since diagnosis
      was unrelated to baseline affect levels as well as affect level changes.
      Additionally, the trajectories of NA and PA were independent of each other. The
      significant correlates of trajectories were gender and CD4 counts, both baseline
      CD4 levels and CD4 changes. CONCLUSION: This study adds to the literature by
      describing affect changes among PLWH and identifying potential correlates of
      these changes, particularly CD4 count and gender. As such, these findings point
      to the potential clinical significance of further research on the roles of these
      variables.

PMID- 30097903
TI  - Effect of cabergoline monotherapy in Cushing's disease: an individual participant
      data meta-analysis.
AB  - CONTEXT: The primary treatment of choice for Cushing's disease (CD) is the
      removal of the pituitary adenoma by transsphenoidal surgery (TSS). The surgical
      failure is seen in up to 75% of cases depending on the experience of the surgeon
      in different studies. Medical therapy is one of the options for the treatment of
      recurrent or persistent CD. METHODOLOGY: The primary outcome of this meta
      analysis was to find the proportion of patients achieving normalisation of 24-h
      urinary free cortisol (remission of CD) following cabergoline monotherapy.
      Literature search was conducted in January 2018 in PubMed/MEDLINE database from
      its date of inception to 31st December 2017. The search strategy used was
      "[(cushing) OR Cushing's] AND cabergoline". Individual participant data were
      extracted from the included studies and risk of bias was analysed by review
      checklist proposed by MOOSE. RESULTS: The individual participant data of 124
      patients from six observational studies were included in this meta-analysis. 92
      patients (74.2%) had past pituitary surgery. The proportion of patients achieving
      remission of CD with cabergoline monotherapy was 39.4% (95% confidence interval
      0.31-0.49; P = 0.026). The previous surgery [odds ratio (OR) 28.4], duration of
      cabergoline monotherapy (OR 1.31) and maximum cabergoline dose (OR 0.19) were
      predictors for remission of CD. Mild and severe side effects were reported in
      37.3% and 5.6% of patients, respectively, during cabergoline monotherapy.
      CONCLUSIONS: This meta-analysis shows that cabergoline monotherapy is a
      reasonable alternative for subjects with persistent or recurrent CD after TSS. It
      can also be used in CD patients either as a bridge therapy while waiting for
      surgery or in those unwilling for surgery or have contraindication to it.

PMID- 30097905
TI  - A Network Pharmacology-Based Analysis of Multi-Target, Multi-Pathway, Multi
      Compound Treatment for Ovarian Serous Cystadenocarcinoma.
AB  - BACKGROUND AND OBJECTIVES: Pharmacological control against ovarian serous
      cystadenocarcinoma has received increasing attention. The purpose of this study
      was to investigate multi-drug treatments as synergetic therapy for ovarian serous
      cystadenocarcinoma and to explore their mechanisms of action by the network
      pharmacology method. METHODS: Genes acting on ovarian serous cystadenocarcinoma
      were first collected from GEPIA and DisGeNET. Gene Ontology annotation, Kyoto
      Encyclopedia of Genes and Genomes pathway, Reactome pathway, and Disease Ontology
      analyses were then conducted. A connectivity map analysis was employed to
      identify compounds as treatment options for ovarian serous cystadenocarcinoma.
      Targets of these compounds were obtained from the Search Tool for Interacting
      Chemicals (STITCH). The intersections between the ovarian serous
      cystadenocarcinoma-related genes and the compound targets were identified.
      Finally, the Kyoto Encyclopedia of Genes and Genomes and Reactome pathways in
      which the overlapped genes participated were selected, and a correspondence
      compound-target pathway network was constructed. RESULTS: A total of 541 ovarian
      serous cystadenocarcinoma-related genes were identified. The functional
      enrichment and pathway analyses indicated that these genes were associated with
      critical tumor-related pathways. Based on the connectivity map analysis, five
      compounds (resveratrol, MG-132, puromycin, 15-delta prostaglandin J2, and
      valproic acid) were determined as treatment agents for ovarian serous
      cystadenocarcinoma. Next, 48 targets of the five compounds were collected.
      Following mapping of the 48 targets to the 541 ovarian serous cystadenocarcinoma
      related genes, we identified six targets (PTGS1, FOS, HMOX1, CASP9, PPARG, and
      ABCB1) as therapeutic targets for ovarian serous cystadenocarcinoma by the five
      compounds. By analysis of the compound-target pathway network, we found the
      synergistic anti-ovarian serous cystadenocarcinoma potential and the underlying
      mechanisms of action of the five compounds. CONCLUSION: In summary, latent drugs
      against ovarian serous cystadenocarcinoma were acquired and their target actions
      and pathways were determined by the network pharmacology strategy, which provides
      a new prospect for medicamentous therapy for ovarian serous cystadenocarcinoma.
      However, further in-depth studies are indispensable to increase the validity of
      this study.

PMID- 30097907
TI  - Attending to behaviorally relevant moments enhances incidental relational memory.
AB  - Memory for the items one has recently encountered is sometimes enhanced in
      divided attention tasks: Attending to behaviorally relevant items, such as a
      target in a detection task, boosts memory for unrelated background items (e.g.,
      scenes or words). However, a central feature of episodic memory is memory for the
      spatiotemporal relationship between items and other elements of an event
      (relational memory), not just the item itself. Three experiments examined whether
      attending to a behaviorally relevant target-item boosts memory for the
      relationship between that item, its features, and a background scene.
      Participants memorized briefly presented scenes. At the same time, they pressed a
      button if a second unrelated item (a figure or face) was a particular target
      color (Experiments 1 and 2) or target gender (Experiment 3) rather than a
      distractor color or gender. Target and distractor items also varied in task
      irrelevant features (shape, location, or facial identity). If attending to
      behaviorally relevant events influences relational memory, then participants
      should be better able to report both target-defining and irrelevant features of
      items that appeared with target-paired scenes rather than distractor-paired
      scenes. This was the case in all experiments: memory was enhanced for the target
      paired scenes as well as the association between a scene and features of the
      paired target-item. Attending to behaviorally relevant moments therefore has
      broader effects on memory encoding than previously thought. In addition to
      boosting memory for unrelated background items, attending to targets facilitates
      relational memory in these tasks.

PMID- 30097908
TI  - Anticholinergic Drugs for Overactive Bladder in Frail Older Patients: The Case
      Against.
AB  - Urinary incontinence (UI) is a common and disabling problem among older people.
      Anticholinergic drugs (ADs) are a pharmacological option recommended for
      overactive bladder or mixed UI when non-pharmacological approaches have failed.
      However, UI is a more prevalent and complex condition in frail older people and
      to simply assume that AD actions are the same across all age groups would be
      wrong. This article reviews evidence for the efficacy and safety of these drugs,
      especially when prescribed for frail older people. Although ADs have a small but
      statistically significant benefit for UI in non-frail people, the vast majority
      choose to discontinue treatment because they feel that the beneficial effects do
      not outweigh the burden of taking the medication. Not only are the most frail
      older people more likely to experience adverse effects but there is also no
      evidence that these drugs are effective for UI. In addition, there is a mounting
      body of evidence that they impair cognitive function. The continued use of ADs in
      frail older people simply does not hold water.

PMID- 30097906
TI  - A Population-Based Pharmacokinetic Model Approach to Pantoprazole Dosing for
      Obese Children and Adolescents.
AB  - BACKGROUND AND AIMS: Pharmacokinetic data for proton pump inhibitors (PPIs), acid
      suppression drugs commonly prescribed to children, are lacking for obese children
      who are at greatest risk for acid-related disease. In a recent multi-center
      investigation, we demonstrated decreased, total body weight adjusted, apparent
      clearance (CL/F) of the PPI pantoprazole for obese children compared with their
      non-obese peers. Subsequently, we developed a population-based pharmacokinetic
      (PopPK) model to characterize pantoprazole disposition and evaluated appropriate
      pantoprazole dosing strategies for obese pediatric patients, using simulation.
      METHODS: Pharmacokinetic data from the only prospective study of PPIs in obese
      children (aged 6-17 years; n = 40) included 273 pantoprazole and 256 pantoprazole
      sulfone plasma concentrations, after single oral-dose administration, and were
      used for pantoprazole model development and covariate analysis (NONMEM(r)). Model
      evaluation was performed via bootstrapping and predictive checks, and the final
      model was applied to simulate systemic pantoprazole exposures for common dosing
      scenarios. RESULTS: A two-compartment PopPK model, which included CYP2C19
      genotype and total body weight, provided the best fit. Resultant, typical, weight
      normalized pantoprazole parameter estimates were different than previously
      reported for children or adults, with significantly reduced pantoprazole CL/F for
      obese children. Of the dosing scenarios evaluated, the weight-tiered approach,
      approved by the US Food and Drug Administration, achieved pantoprazole exposures
      [area under the curve (AUC0-infinity)] within ranges previously reported as
      therapeutic, without over- or under-prediction for obese children. CONCLUSIONS:
      Our data argue against empiric dose escalation of PPIs for obese children and
      support current FDA-approved pediatric weight-tiered dosing for pantoprazole;
      however, 3- to 5-fold inter-individual variability in pantoprazole AUC0-infinity
      remained using this dosing approach.

PMID- 30097909
TI  - Anticholinergics for Overactive Bladder in Frail and Medically Complex Older
      People: The Case For.
AB  - Overactive bladder (OAB) is a common, troublesome condition affecting the lives
      of many older people. When pharmacotherapy is considered, antimuscarinics remain
      the mainstay for treatment. Bladder antimuscarinics are effective in the relief
      of symptoms for OAB and treatment leads to significant improvements in quality of
      life for those with the condition. However, many older people (> 65 years) with
      OAB are in later life (> 75 years) and a proportion of these will either be
      medically complex, with multiple comorbid conditions, or frail. This article
      discusses the evidence for OAB treatment in the frail or medically complex
      elderly, outlines where caution should be exercised, giving examples from the
      recent literature, and advocates for an active approach for this group, who are
      often left without any treatment.

PMID- 30097910
TI  - Non-response to Cardiac Resynchronization Therapy.
AB  - PURPOSE OF REVIEW: Cardiac resynchronization therapy (CRT) is an effective
      treatment option for therapy-refractory mild to severe heart failure (HF)
      patients with reduced ejection fraction and left ventricular (LV) conduction
      delay. Multiple clinical trials have shown that CRT improves cardiac function and
      overall quality of life, as well as reduces HF hospitalizations, health care
      costs, and mortality. RECENT FINDINGS: Despite its effectiveness, the "non
      response" rate to CRT is around 30%, remaining a major challenge that faces
      electrophysiologists and researchers. It has been recently suggested that the
      etiology of CRT non-response is multifactorial, and it requires a multifaceted
      approach to address it. In this focused review, we will summarize the definitions
      of CRT non-response, identify key factors for CRT non-response, and offer a
      simplified framework to address CRT non-response with the main goal of improving
      CRT outcomes.

PMID- 30097911
TI  - Sleep quality as predictor of BMI in non-depressed caregivers of people with
      dementia.
AB  - PURPOSE: Although most cross-sectional and longitudinal studies of children and
      adolescents have found a link between short duration of sleep and obesity, the
      literature related to adults provides a non-consensual framework. The aim of the
      present study was to examine the association between sleep quality and BMI in a
      population of caregivers looking after people suffering from dementia, with a
      view to identifying the moderating role of depressive symptoms in the
      relationship between sleep problems and BMI. METHODS: A total of 117 subjects
      took part in the study, filling in a Sociodemographic Questionnaire, the
      Pittsburgh Sleep Quality Index, the Eating behavior Questionnaire and The Center
      for Epidemiologic Studies-Depression. RESULTS: Depressive symptoms were greater
      in females than in males. The sample was divided into two subgroups based on
      depressive-symptom scores. Only within the subsample with low depressive
      symptoms, higher sleep disturbances influenced BMI positively. Within this
      subsample of participants with low depressive symptoms, the variables that seem
      to play a pivotal role in explaining a high BMI are: female gender, sleep
      problems, and diet quality, while within the subsample with high depressive
      symptoms only the female gender factor was found to influence BMI. CONCLUSIONS:
      Depressive symptoms seem to act as moderators in the relationship between sleep
      and BMI. They should be evaluated to identify the risk of high BMI, and to
      differentiate clinical intervention, at least in this population, which
      experiences the stress of caregiving chronically, though not suffering from
      clinical eating disorders. LEVEL OF EVIDENCE: Level II, cross-sectional study.

PMID- 30097913
TI  - Health-related quality of life and the physician-patient alliance: a preliminary
      investigation of ultra-brief, real-time measures for primary care.
AB  - PURPOSE: Many psychometrically sound measures exist but feasibility makes real
      time use difficult. This study validates two ultra-brief, patient-rated
      instruments, the Wellness Rating Scale (WRS) and the Provider Alliance Scale
      (PAS). METHODS: The WRS and the EuroQol visual analogue scale (EQ VAS) were
      completed by patients in a primary care practice (n = 97) and a non-clinical
      sample of graduate students (n = 122). The WRS and the Patient-Completed Health
      Outcome Measures Information System-Global 10 (PROMIS) were completed by patients
      in a primary care setting (n = 305). The WRS and PROMIS were also administered to
      graduate students (n = 158). The PAS and the Patient Physician Working Alliance
      were administered to a primary care sample of 40 and a retrospective sample of
      students (n = 228). RESULTS: The WRS generated reliable scores, with coefficient
      alphas ranging from .83 to .91. Bivariate correlations between the WRS and the EQ
      VAS (r = .55-.75) and PROMIS (r = .64-73) indicate moderate-to-strong concurrent
      validity. The larger coefficients were with patient samples. Construct validity
      was evidenced by higher levels of distress for chronic conditions as well as for
      clinical samples. The PAS achieved an alpha of .94 for the primary care sample
      and .87 for the retrospective sample and bivariate correlations (r = .61-.72)
      indicate moderate-to-strong evidence of concurrent validity. CONCLUSIONS: The WRS
      and PAS demonstrate sufficient reliability and validity to move to the next phase
      of research: a randomized clinical trial comparing the use of real-time feedback
      from the two measures to treatment as usual targeting outcomes of chronic disease
      patients.

PMID- 30097912
TI  - Automatic 13C chemical shift reference correction for unassigned protein NMR
      spectra.
AB  - Poor chemical shift referencing, especially for 13C in protein Nuclear Magnetic
      Resonance (NMR) experiments, fundamentally limits and even prevents effective
      study of biomacromolecules via NMR, including protein structure determination and
      analysis of protein dynamics. To solve this problem, we constructed a Bayesian
      probabilistic framework that circumvents the limitations of previous reference
      correction methods that required protein resonance assignment and/or three
      dimensional protein structure. Our algorithm named Bayesian Model Optimized
      Reference Correction (BaMORC) can detect and correct 13C chemical shift
      referencing errors before the protein resonance assignment step of analysis and
      without three-dimensional structure. By combining the BaMORC methodology with a
      new intra-peaklist grouping algorithm, we created a combined method called
      Unassigned BaMORC that utilizes only unassigned experimental peak lists and the
      amino acid sequence. Unassigned BaMORC kept all experimental three-dimensional
      HN(CO)CACB-type peak lists tested within +/- 0.4 ppm of the correct 13C reference
      value. On a much larger unassigned chemical shift test set, the base method kept
      13C chemical shift referencing errors to within +/- 0.45 ppm at a 90% confidence
      interval. With chemical shift assignments, Assigned BaMORC can detect and correct
      13C chemical shift referencing errors to within +/- 0.22 at a 90% confidence
      interval. Therefore, Unassigned BaMORC can correct 13C chemical shift referencing
      errors when it will have the most impact, right before protein resonance
      assignment and other downstream analyses are started. After assignment, chemical
      shift reference correction can be further refined with Assigned BaMORC. These new
      methods will allow non-NMR experts to detect and correct 13C referencing error at
      critical early data analysis steps, lowering the bar of NMR expertise required
      for effective protein NMR analysis.

PMID- 30097915
TI  - The Duplexing of the Genetic Code and Sequence-Dependent DNA Geometry.
AB  - It is well known that sequences of bases in DNA are translated into sequences of
      amino acids in cells via the genetic code. More recently, it has been discovered
      that the sequence of DNA bases also influences the geometry and deformability of
      the DNA. These two correspondences represent a naturally arising example of
      duplexed codes, providing two different ways of interpreting the same DNA
      sequence. This paper will set up the notation and basic results necessary to
      mathematically investigate the relationship between these two natural DNA codes.
      It then undertakes two very different such investigations: one graphical approach
      based only on expected values and another analytic approach incorporating the
      deformability of the DNA molecule and approximating the mutual information of the
      two codes. Special emphasis is paid to whether there is evidence that pressure to
      maximize the duplexing efficiency influenced the evolution of the genetic code.
      Disappointingly, the results fail to support the hypothesis that the genetic code
      was influenced in this way. In fact, applying both methods to samples of
      realistic alternative genetic codes shows that the duplexing of the genetic code
      found in nature is just slightly less efficient than average. The implications of
      this negative result are considered in the final section of the paper.

PMID- 30097914
TI  - Impact of untreated dental caries severity on the quality of life of preschool
      children and their families: a cross-sectional study.
AB  - PURPOSE: Untreated dental caries is a persistent oral problem among preschool
      children. Although there is vast evidence regarding the impact of dental caries
      on oral health-related quality of life (OHRQoL) in this age group, evidence on
      the impact of untreated caries severity is scarce. The purpose of this study was
      to investigate the impact of untreated caries severity on the OHRQoL of preschool
      children and their families. METHODS: A cross-sectional study was conducted with
      563 individuals in the city of Goiania, Brazil. Data were collected through
      interviews with parents/caregivers and clinical examinations of their children.
      The OHRQoL was measured by the Brazilian version of the Early Childhood Oral
      Health Impact Scale. Untreated dental caries severity was assessed using
      validated indices. Other independent variables were socioeconomic, toothache
      prevalence, and the questionnaire respondent. Statistical analysis involved
      bivariate comparisons and Poisson regression analyses. RESULTS: A higher
      prevalence of impact on OHRQoL was found among preschool children with untreated
      dental caries with clinical consequences (PR 1.31; 95% CI 1.01-1.70) compared to
      those without caries; those aged 5 years (PR 1.47; 95% CI 1.18-1.82), compared to
      those aged two; and those with a toothache (PR 1.54; 95% CI 1.34-1.76), compared
      to those without toothache. Moreover, fathers (PR 0.71; 95% CI 0.55-0.92) and
      other respondents (PR 0.70; 95% CI 0.52-0.96) perceived less impact on the OHRQoL
      in comparison to mothers. CONCLUSIONS: Severe untreated dental caries with
      clinical consequences had a negative impact on the children's OHRQoL, regardless
      of toothache and socioeconomic factors.

PMID- 30097916
TI  - Spatial Moment Description of Birth-Death-Movement Processes Incorporating the
      Effects of Crowding and Obstacles.
AB  - Birth-death-movement processes, modulated by interactions between individuals,
      are fundamental to many cell biology processes. A key feature of the movement of
      cells within in vivo environments is the interactions between motile cells and
      stationary obstacles. Here we propose a multi-species model of individual-level
      motility, proliferation and death. This model is a spatial birth-death-movement
      stochastic process, a class of individual-based model (IBM) that is amenable to
      mathematical analysis. We present the IBM in a general multi-species framework
      and then focus on the case of a population of motile, proliferative agents in an
      environment populated by stationary, non-proliferative obstacles. To analyse the
      IBM, we derive a system of spatial moment equations governing the evolution of
      the density of agents and the density of pairs of agents. This approach avoids
      making the usual mean-field assumption so that our models can be used to study
      the formation of spatial structure, such as clustering and aggregation, and to
      understand how spatial structure influences population-level outcomes. Overall
      the spatial moment model provides a reasonably accurate prediction of the system
      dynamics, including important effects such as how varying the properties of the
      obstacles leads to different spatial patterns in the population of agents.

PMID- 30097917
TI  - The Persistence of a Local Dialect When a National Standard Language is Present:
      An Evolutionary Dynamics Model of Cultural Diversity.
AB  - In recent decades, cultural diversity loss has been a growing issue, which can be
      analyzed mathematically through the use of the formalism of the theory of
      cultural evolution. We here study the evolutionary dynamics of dialects in order
      to find the key processes for mitigating the loss of language diversity. We
      define dialects as different speech systems of the same language which are
      mutually intelligible. Specifically, we focus on the survival of a local dialect
      when competing against a national standard language, with the latter giving an
      advantage in occupational and economic contexts. We assume individuals may use
      different dialects, in response to two different situations: they may use the
      national language in a formal workplace, while they may use a local dialect in
      family or close friend meetings. We consider the choice of a dialect is guided by
      two forces: (1) differential attractiveness of the local/standard language and
      (2) willingness to speak the same dialect (conformity factor) inside a private
      group. We found that the evolutionary outcome critically depends on how
      conformity works. Conformity enhances the effect of differential attractiveness
      between the local dialect and the standard language if conformity works favoring
      only those states in which all speakers use the same dialect (unanimity pressure
      model), but conformity has no effect at all if it works in proportion to the
      fraction among peers (peer pressure model).

PMID- 30097918
TI  - Applications of WKB and Fokker-Planck Methods in Analyzing Population Extinction
      Driven by Weak Demographic Fluctuations.
AB  - In large but finite populations, weak demographic stochasticity due to random
      birth and death events can lead to population extinction. The process is
      analogous to the escaping problem of trapped particles under random forces.
      Methods widely used in studying such physical systems, for instance, Wentzel
      Kramers-Brillouin (WKB) and Fokker-Planck methods, can be applied to solve
      similar biological problems. In this article, we comparatively analyse
      applications of WKB and Fokker-Planck methods to some typical stochastic
      population dynamical models, including the logistic growth, endemic SIR, predator
      prey, and competitive Lotka-Volterra models. The mean extinction time strongly
      depends on the nature of the corresponding deterministic fixed point(s). For
      different types of fixed points, the extinction can be driven either by rare
      events or typical Gaussian fluctuations. In the former case, the large deviation
      function that governs the distribution of rare events can be well-approximated by
      the WKB method in the weak noise limit. In the later case, the simpler Fokker
      Planck approximation approach is also appropriate.

PMID- 30097919
TI  - Spreading Waves in a Farmers and Hunter-Gatherers Model of the Neolithic
      Transition in Europe.
AB  - The Neolithic transition began the spread of early agriculture throughout Europe
      through interactions between farmers and hunter-gatherers about 10,000 years ago.
      Archeological evidence produced by radiocarbon dating indicates that the
      expanding velocity of farming is roughly constant all over Europe. Theoretical
      understanding of such evidence has been performed from mathematical modeling
      viewpoint. However, the expanding velocity determined by existing modeling
      approaches is faster than the observed velocity. For understanding this
      difference, we propose a three-component reaction-diffusion system which consists
      of two different types of farmers (sedentary and migratory) and hunter-gatherers
      from the viewpoint of the influence of farming technology. Our purpose is to
      study the relation between the expanding velocity of farmers and the farming
      technology parameter (say, [Formula: see text]). In this paper, we mainly focus
      on the one-dimensional traveling wave solution with minimal velocity and show
      that the minimal velocity decreases, as [Formula: see text] increases. This can
      be compatible with the observed velocity when farming technology is developed.
      Our results suggest that the reason for the slowdown of the Neolithic transition
      might be related to the increase in the development of farming technology.

PMID- 30097920
TI  - Pattern Formation in the Longevity-Related Expression of Heat Shock Protein-16.2
      in Caenorhabditis elegans.
AB  - Aging in Caenorhabditis elegans is controlled, in part, by the insulin-like
      signaling and heat shock response pathways. Following thermal stress, expression
      levels of small heat shock protein-16.2 show a spatial patterning across the 20
      intestinal cells that reside along the length of the worm. Here, we present a
      hypothesized mechanism that could lead to this patterned response and develop a
      mathematical model of this system to test our hypothesis. We propose that the
      patterned expression of heat shock protein is caused by a diffusion-driven
      instability within the pseudocoelom, or fluid-filled cavity, that borders the
      intestinal cells in C. elegans. This instability is due to the interactions
      between two classes of insulin-like peptides that serve antagonistic roles. We
      examine output from the developed model and compare it to experimental data on
      heat shock protein expression. Given biologically bounded parameters, the model
      presented is capable of producing patterns similar to what is observed
      experimentally and provides a first step in mathematically modeling aging-related
      mechanisms in C. elegans.

PMID- 30097923
TI  - Protein Stains and Applications.
AB  - Staining of proteins separated on gels provides the basis for determination of
      the critical properties of these biopolymers, such as their molecular weight
      and/or charge. Detection of proteins on gels and blots require stains. These
      stains vary in sensitivity, ease of use, color, stability, versatility, and
      specificity. This review discusses different stains and applications with details
      on how to use the stains, and advantages and disadvantages of each stain. It also
      compiles some important points to be considered in imaging and evaluation.
      Commonly used colorimetric and fluorescent dyes for general protein staining, and
      stains that detect posttranslational modification-specific detection methods are
      also discussed.

PMID- 30097925
TI  - Multicolored Prestained Standard Protein Marker Generation Using a Variety of
      Remazol Dyes for Easy Visualization of Protein Bands During SDS-PAGE.
AB  - Isolation and detection of a specific protein from a complex mixture of proteins
      using molecular sieves provided by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE) is a widely used technique in molecular biology and
      biochemistry. The detection is achieved usually by running prestained standard
      markers along with the sample protein mixture. Multicolored standard markers are
      preferred compared to fluorescent labeled or single colored markers as it allows
      easy visualization of separation of a specific protein band during SDS-PAGE. In
      addition, these colored markers show evidence for the transfer of protein bands
      on the membrane in western blotting technique. This review describes a very
      simple, inexpensive and easy method of prestaining specific proteins with
      different colors using a variety of Remazol dyes.

PMID- 30097924
TI  - The Roles of Acetic Acid and Methanol During Fixing and Staining Proteins in an
      SDS-Polyacrylamide Electrophoresis Gel.
AB  - After SDS-polyacrylamide gel electrophoresis proteins are "fixed" in the gel to
      prevent dispersion of the proteins and visualized by staining with a chromogenic
      dye. Dyes like Coomassie Blue R-250, Amido Black, and Direct Red 81 are usually
      dissolved in an acetic acid-methanol-water mixture. During staining the dye
      solvent mixture infuses the gel and interacts with the protein. Acetic acid and
      methanol denature the protein and provide an acidic environment enhancing the
      interactions with dyes. After staining, the dye that is in the gel and not bound
      to the protein, is removed using the solvent medium the dyes were dissolved in.
      Over 2-3 h the solution surrounding the gel becomes colored, the gel becomes
      lighter and the protein bands remain dark and the contrast against the
      surrounding gel improves. This chapter describes how each of the individual
      components in the dye solution interact with the protein resulting in a stained
      protein band in a clear SDS-polyacrylamide electrophoresis gel.

PMID- 30097926
TI  - Coomassie Brilliant Blue Staining of Polyacrylamide Gels.
AB  - In the past a series of staining procedures for proteins were published. Still,
      the most commonly used staining dye for proteins is Coomassie Brilliant Blue. The
      major reason is that Coomassie Brilliant Blue staining is simple, fast, and
      sensitive. As Coomassie Brilliant Blue is almost insoluble in water a series of
      procedures including colloidal aqueous procedures has been described.

PMID- 30097928
TI  - Application of Heat to Quickly Stain and Destain Proteins Stained with Coomassie
      Blue.
AB  - Proteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
      have been visualized reliably by staining with Coomassie Brilliant Blue. In this
      chapter, we show that it is possible to drastically reduce protein staining and
      destaining time, while simultaneously increasing detection sensitivity, with the
      application of heat. It took 5 min to stain proteins at 55, 62.5, or 70  degrees
      C for a 1.5 mm gel, while it took 45, 45, and 20 min respectively for destaining.
      The time for staining was 1 min for a 0.8 mm gel at 65  degrees C, 2 min at 60 
      degrees C and 5 min at 55  degrees C. The destaining of proteins separated on a
      0.8 mm gel took 8, 15, and 20 min at 65, 60, and 55  degrees C respectively.
      Proteins can be stained and destained rapidly with the use of heat, while
      enhancing detection sensitivity.

PMID- 30097927
TI  - A Simple, Time-Saving Dye Staining of Proteins in Sodium Dodecyl Sulfate
      Polyacrylamide Gel Using Coomassie Blue.
AB  - Most traditional post-electrophoretic processes need several hours to several
      days to finish the whole staining process and traditional staining solutions all
      contain methanol, acetic acid, or phosphoric acid, which not only produce the
      unpleasant smell but also cause environmental pollution. Here a fixation-free,
      fast protein staining method in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis using Coomassie blue is described. The protocol includes only
      staining and quick washing steps, can be completed in 0.5 h. It has a sensitivity
      of 10 ng. In addition, the dye stain does not contain any acid or methanol.

PMID- 30097922
TI  - MiR-499/PRDM16 axis modulates the adipogenic differentiation of mouse skeletal
      muscle satellite cells.
AB  - Obesity is associated with increased risks of diverse diseases; brown adipose
      tissue (BAT) can increase energy expenditure and protect against obesity by
      increasing the decomposition of white adipose tissue (WAT) to enhance the non
      coupled oxidative phosphorylation of fatty acid in adipocytes and contributes to
      weight loss. However, BAT is abundant in only small rodents and newborn humans,
      but not in adults. PRDM16 is a key factor that induces the differentiation of
      skeletal muscle precursors to brown adipocytes and simultaneously inhibits
      myogenic differentiation. In the present study, we set insulin-induced skeletal
      muscle satellite cells (SMSCs) adipogenic differentiation model, as confirmed by
      the contents of adipogenic markers PRDM16, UCP1 and PGC1alpha and myogenic
      markers MyoD1 and MyoG. We selected miR-499 as candidate miRNA, which might
      regulate PRDM16 to affect SMSCs adipogenic differentiation. Possibly through
      directly binding to PRDM16 3'-UTR, miR-499 negatively regulated PRDM16 expression
      and hindered SMSCs adipogenic differentiation by reducing adipogenic markers
      PRDM16, UCP1 and PGC1alpha and increasing myogenic markers MyoD1 and MyoG. PRDM16
      overexpression could partially reverse the effect of miR-499 on the above markers
      and SMSCs adipogenic differentiation. Taken together, miR-499/PRDM16 axis can
      affect the balance between SMSC myogenic and adipogenic differentiation,
      targeting miR-499 to rescue PRDM16 expression, thus promoting SMSCs adipogenic
      differentiation may be a promising strategy for obesity treatment.

PMID- 30097929
TI  - Silver Staining Techniques of Polyacrylamide Gels.
AB  - After SDS-polyacrylamide gel electrophoresis the separated proteins have to be
      visualized by staining the gel. The same is true after transfer of separated
      proteins to a blotting membrane in order to verify an efficient transfer and to
      visualize the amount of protein(s) remaining in the gel. Several different
      staining techniques exist for staining of proteins in SDS-polyacrylamide gels.
      The sensitivity of these staining procedures are different, also the expenditure
      of time and other aspects. Still, silver staining is among the most sensitive and
      reliable staining technique. Because this technique was developed in the 1970s, a
      huge number of variations exist. Here, we will provide three variations, which
      are robust and easy to perform.

PMID- 30097930
TI  - Counterion Dye Staining of Proteins in One- and Two-Dimensional Sodium Dodecyl
      Sulfate-Polyacrylamide Gel Electrophoresis and Tryptic Gel Digestion of Stained
      Protein for Mass Spectrometry.
AB  - A fast and matrix-assisted laser desorption/ionization-mass spectrometry
      compatible protein staining method in one- and two-dimensional sodium dodecyl
      sulfate-polyacrylamide gel electrophoresis is described. It is based on the
      counterion dye staining method that employs oppositely charged two dyes, zincon
      and ethyl violet to form an ion-pair complex. The protocol including fixing,
      staining, and quick washing steps can be completed in 1-1.5 h depending upon gel
      thickness. It has the sensitivity comparable to the colloidal Coomassie Brilliant
      Blue G stain using phosphoric acid as a component of staining solution (4-8 ng).
      The counterion dye stain does not induce protein modifications that complicate
      interpretation of peptide mapping data from mass spectrometry. Considering the
      speed, sensitivity, and compatibility with mass spectrometry, the counterion dye
      stain may be more practical than any other dye-based protein stains for routine
      proteomic researches.

PMID- 30097931
TI  - Detection of Phosphoproteins in Sodium Dodecyl Sulfate-Polyacrylamide Gel
      Electrophoresis Using 8-Quinolinol Stain.
AB  - In order to detect phosphoproteins in sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE), an easy and fast fluorescent detection method is
      described. 8-Quinolinol can form ternary complexes in the gel matrix contributed
      by the affinity of aluminum ion to the phosphate groups on the proteins and the
      metal chelating property of 8-Quinolinol, exhibiting strong fluorescence in
      ultraviolet light. It can visualize as little as 4-8 ng of alpha-casein and beta
      casein, 15-31 ng of ovalbumin and kappa-casein within 70 min. The approach
      utilizing 8-quinolinol could be an alternative staining method for
      phosphoproteomics.

PMID- 30097932
TI  - Microwave-Assisted Protein Staining, Destaining, and In-Gel/In-Solution Digestion
      of Proteins.
AB  - Rapid evolution of state-of-the-art proteomic analyses has encompassed
      development of high-throughput analytical instrumentation and bioinformatic
      tools. However, recently there has been a particular emphasis on increasing the
      throughput of sample preparation, which has become one of the rate-limiting steps
      in protein characterization workflows. Researchers have been investigating
      alternative methods to conventional convection oven incubations to try and reduce
      sample preparation time for protein characterization. Several protocols have
      appeared in the literature, which employ microwave irradiation as a tool for the
      preparation of biological samples for subsequent characterization by a variety of
      analytical techniques. In this chapter, techniques for microwave-assisted protein
      staining, destaining, and digestion are described. In general, the application of
      microwave-assisted technologies resulted in the drastic reduction of overall
      sample preparation time, though discrepancies in the reproducibility of several
      published digestion protocols still remain to be clarified.

PMID- 30097933
TI  - Fluorescent Staining of Gels.
AB  - Certain transition metal complexes show intensive fluorescence when bound to
      proteins. They can be used to stain gels after electrophoresis with a sensitivity
      approaching that of silver staining, but in a much simpler and more reproducible
      procedure. Stains can be prepared easily and at a fraction of the cost of
      commercially available reagents. Hydrophobic dyes can be used to stain gels
      without fixing; they do not interfere with later blotting or electroelution.

PMID- 30097934
TI  - A Single-Step Simultaneous Protein Staining Procedure for Polyacrylamide Gels and
      Nitrocellulose Membranes by Alta During Western Blot Analysis.
AB  - A simple method for staining of proteins simultaneously on sodium dodecyl sulfate
      (SDS)-polyacrylamide gels and nitrocellulose membranes by Alta during Western
      blot analysis is described. A 5% solution of Alta, a commercially available
      cosmetic preparation, is added in the upper tank buffer during electrophoresis.
      On completion of electrophoresis, the gel is washed in distilled water, viewed on
      a white light plate and a transilluminator to photograph the protein profiles.
      The gel is processed for Western blot transfer of proteins onto a nitrocellulose
      membrane, and upon completion, the protein profiles on the membrane are viewed
      and photographed as stated above. The membrane can then be processed for
      immunostaining as per the standard procedure. Thus, the staining procedure using
      Alta is simple, rapid (without any need of destaining) and cost-effective.

PMID- 30097936
TI  - Detection of Glycoproteins in Polyacrylamide Gels Using Pro-Q Emerald 300 Dye, a
      Fluorescent Periodate Schiff-Base Stain.
AB  - Pro-Q Emerald 300 glycoprotein stain generates a bright-green fluorescent signal
      upon reacting with periodic acid-oxidized carbohydrate groups on proteins. With
      this dye it is possible to detect proteins directly in the gel without the need
      to transfer them to a membrane. This dye is more sensitive than the standard
      periodic-acid Schiff's base which uses acidic fuchsin dye.

PMID- 30097935
TI  - TEMED Enhanced Photoluminescent Imaging of Human Serum Proteins by Quantum Dots
      After PAGE.
AB  - Polyacrylamide gel electrophoresis (PAGE) has become one of the most powerful and
      widely used separation techniques for complex biological samples, whose
      traditional detection methods include organic dye or silver staining. For simple,
      convenient, and ultrasensitive detection of proteins after PAGE, a novel enhanced
      photoluminescent (PL) imaging method was developed. Thioglycolic acid (TGA)
      capped CdTe quantum dots (QDs) and the enhancer reagent
      tetramethylethylenediamine (TEMED) were introduced, achieving the direct
      detection of various proteins in native 1-DE, 2-DE and SDS-PAGE. Here we describe
      the general protocol of TEMED enhanced PL imaging by QDs, including materials,
      practical procedures, and some notes.

PMID- 30097937
TI  - Curcumin/Turmeric as an Environment-Friendly Protein Gel Stain.
AB  - Curcumin, the main curcuminoid in food spice turmeric, is insoluble in water at
      room temperature. We showed that curcumin can be solubilized in water with the
      application of heat (100  degrees C). Here we demonstrate that heat-solubilized
      curcumin can serve as a nontoxic and environment-friendly
      fluorescent/colorimetric reversible protein stain. Curcumin, the yellow pigment
      found in the rhizomes of the perennial herb Curcuma longa (turmeric), is
      insoluble in aqueous solvents. However, heat solubilization in water renders 1.5%
      of curcumin soluble. Curcumin solubilized by ethanol or alkali is ineffective in
      staining proteins. Heat-solubilized curry spice turmeric also stains proteins.
      Staining is achieved in 30 min, with a sensitivity almost equaling that of
      Coomassie Brilliant Blue (CBB). Destaining is not required and excess
      curcumin/turmeric can be discarded into the sink. Binding of proteins by silver
      inhibits curcumin binding, suggesting similarity of protein binding by silver and
      curcumin. It costs $1.5-2.0 to stain a mini-gel with curcumin, while turmeric
      costs less than 0.005 cent. CBB staining/destaining costs about two cents.
      Curcumin/turmeric, thus, can serve as an ideal nontoxic protein stain.

PMID- 30097938
TI  - Detection of Multiple Enzymes in Fermentation Broth Using Single PAGE Analysis.
AB  - Activity staining or zymography is a technique to detect enzymes based on their
      function/activity toward a specific substrate. Multiple enzyme-producing microbes
      secrete enzymes along with other proteins at varying time points during
      fermentation. The technique of zymography can be used to detect functionality of
      enzymes in complex protein/other enzyme mixtures. The protein bands corresponding
      to specific enzyme among other enzymes/proteins can be located by polyacrylamide
      gel electrophoresis (PAGE) followed by zymogram analysis. This can be employed to
      locate the secretion pattern of protein/enzyme from intracellular region to
      extracellular medium. Here we describe simple method for detection and cellular
      localization of esterases and protease secreted by single microbial strain in one
      PAGE gel.

PMID- 30097939
TI  - Revisit of Imidazole-Zinc Reverse Stain for Protein Polyacrylamide Gel
      Electrophoresis.
AB  - Imidazole-zinc reverse stain (ZN stain) is known for high sensitivity, ease of
      use, and cost-effective feature. ZN stain is compatible to many experiments of
      which those are proteomics-related in particular. Here, we describe the ZN
      staining procedures and the subsequent procedures incorporated in detail, along
      with the improvements of setup in aspects of visualization and documentation for
      postprocessing ZN stained gel images.

PMID- 30097940
TI  - A One-Step Staining Protocol for In-Gel Fluorescent Visualization of Proteins.
AB  - Native polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS)
      PAGE are among the most frequently applied techniques in protein analysis. Here
      we describe a fast one-step method for fluorescent visualization of proteins.
      Following PAGE, gels are soaked in solution of potassium ferricyanide (100 mM) in
      1 M NaOH, and are kept in the dark for 30 min. Gels are then transferred to water
      and scanned. The sensitivity of the method is comparable with standard Coomassie
      Brilliant Blue staining.

PMID- 30097941
TI  - Ten Minute Stain to Detect Proteins in Polyacrylamide Electrophoresis Gels with
      Direct Red 81 and Amido Black.
AB  - Proteins separated by SDS-polyacrylamide gel electrophoresis need to be stained
      with organic dyes to be visualized. Once stained the intensity of each stained
      protein band can be used to compare the differences in protein concentration and
      to measure the relative concentration of any protein band. The most popular
      standard protein staining is with Coomassie Blue R-250 which takes an hour to
      stain proteins to saturation and several hours to remove background staining.
      Direct Red 81 and Amido Black stain proteins within 2.5 min and staining is
      complete by 10 min. Here the rapid staining of proteins with Direct Red 81 and
      Amido Black in comparison to staining with Coomassie Blue R-250 is described.

PMID- 30097942
TI  - In-Gel Protein Phosphatase Assay Using Fluorogenic Substrates.
AB  - Protein phosphorylation plays important roles in regulating a variety of
      biological processes in animals, plants, and microorganisms. Therefore, it is
      important to use appropriate techniques to detect and analyze protein kinases and
      protein phosphatases. In this chapter, we describe the method to detect protein
      phosphatase activities using fluorogenic substrates such as 4-methylumbelliferyl
      phosphate (MUP) after separating proteins by one-dimensional or two-dimensional
      polyacrylamide gel electrophoresis.

PMID- 30097943
TI  - Detection of Proteins in Polyacrylamide Gels via Prelabeling by Isatoic
      Anhydride.
AB  - Fluorescent methods for staining of proteins in polyacrylamide gels are obtaining
      increasing attention due to their advantages including high sensitivity and
      rapidness. In the present chapter we describe, step by step, a rapid and
      inexpensive fluorescent prelabeling method based on derivatization of proteins
      with isatoic anhydride. This method allows researchers to detect less than 2 ng
      of standard proteins per band in less than 15 min. Although this method is
      sensitive, inexpensive, rapid, compatible with most of common biological reagents
      and is able to detect proteins in crude cell extract, covalent binding of isatoic
      anhydride to protein lysine residues makes it unsuitable for processes in which
      post-electrophoresis analysis is required. Moreover, isatoic anhydride
      derivatization induces a small band broadening.

PMID- 30097944
TI  - Fluorescent Protein Visualization Immediately After Gel Electrophoresis Using an
      In-Gel Trichloroethanol Photoreaction with Tryptophan.
AB  - SDS-polyacrylamide gel electrophoresis (SDS-PAGE) is one of the essential
      techniques in molecular biology and biochemistry laboratories and requires rapid
      visualization methods for efficient sample analysis. Proteins on polyacrylamide
      gels can be visualized within 5 min via the photoreaction of tryptophan with
      trichloroethanol. This process does not require protein fixation, staining, or
      destaining. In this method polyacrylamide gels are prepared by adding
      trichloroethanol before polymerization. After electrophoresis, the gel is
      immediately activated on a standard UV transilluminator and the fluorescently
      labeled proteins are imaged. The reaction is based on the photoreaction of
      trichloroethanol with tryptophan residues within the protein. This generates a
      visible blue-green fluorescence (~500 nm) that is accurately imaged. Here we
      describe the preparation of Tris-glycine and Tris-tricine SDS-polyacrylamide gels
      with trichloroethanol and the photoreaction and visualization of tryptophan
      containing proteins.

PMID- 30097945
TI  - Direct Immunodetection of Antigens Within the Precast Polyacrylamide Gel.
AB  - Western blotting is one of the few basic techniques widely used in the study of
      proteins in life science research. Despite its prevalence, the procedure has
      remained practically unchanged for more than 20 years. Although the method is
      viewed as being error-prone and as requiring excessive hands-on time, it is still
      widely accepted because it provides sensitive and direct information about the
      protein characteristics. The process is attractive to researchers because it
      reduces the investment in instrumentation and set up. Here we describe a
      procedure that eliminates the transfer step of western blotting and allows for
      antigen detection directly within the polyacrylamide gel, thus minimizing the
      investment necessary for setting up western blotting.

PMID- 30097946
TI  - Zymographic Determination of Intrinsic Specific Activity of Oxidases in the
      Presence of Interfering Proteins.
AB  - Zymography on peroxidase-entrapped gels enables the determination of the
      intrinsic specific activity (ISA) of H2O2-producing oxidases in the presence of
      interfering enzymes including catalase (decomposing hydrogen peroxide). To reveal
      the searched oxidase, the zymography gel is incubated first in the developing
      solution containing the appropriate substrate of the oxidase and an oxidizable
      chromogen such as o-phenylenediamine (o-PDA) peroxidase substrate. The
      zymographic gel, after image analysis, can be restained by Coomassie Blue for
      molecular weights, for the whole electrophoretic pattern and for the protein
      concentration, thus allowing for the determination of oxidase ISA.

PMID- 30097947
TI  - A Simple Method for Detecting Phosphorylation of Proteins by Using Zn2+-Phos-Tag
      SDS-PAGE at Neutral pH.
AB  - Zn2+-Phos-tag SDS-PAGE at neutral pH is a novel and simple method for analysis
      and separation of phosphorylated forms of proteins from their nonphosphorylated
      forms. This technique exploits the use of a dinuclear metal complex of 1,3
      bis[bis(pyridin-2-ylmethyl)amino]propan-2-olate which acts as a phosphate-binding
      tag, having the capacity to incorporate two zinc metal ions which could then bind
      to phosphomonoester dianion as a bridging ligand. The acrylamide-pendant Zn2+
      Phos-tag provides a phosphate affinity on simple SDS-PAGE gel for detection of
      mobility shift in phosphorylated proteins as compared to their nonphosphorylated
      forms. The technique is based on the principle that Zn2+-Phos-tag bound
      phosphorylated protein has a slower migration rate on the gel as compared to
      unbound nonphosphorylated proteins and are thus separated on the gel. Zn2+-Phos
      tag SDS-PAGE was developed by improving the Mn2+-Phos-tag SDS-PAGE as the latter
      was unsuccessful in showing a mobility shift in some proteins such as Tau and
      pepsin. Additionally, the use of neutral pH instead of alkaline pH gives almost
      about 6 months of stability to the gels as compared to gels in alkaline pH which
      were quite unstable. Therefore, this Zn2+-Phos-tag SDS-PAGE method is simple,
      reliable and convenient for phosphate-affinity SDS-PAGE.

PMID- 30097948
TI  - Principle and Method of Silver Staining of Proteins Separated by Sodium Dodecyl
      Sulfate-Polyacrylamide Gel Electrophoresis.
AB  - Silver staining is an excellent technique for detecting proteins which are
      separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis due to its
      efficiency of detecting proteins present in nanograms. The technique is based on
      the simple principle that selective reduction of silver into metallic silver
      occurs at the initiation site in the close proximity of protein molecules. The
      staining process sequentially consists of protein fixation, sensitization,
      washing, silver impregnation, and finally development of image. Depending upon
      the amount of silver incorporated into the protein bands, different color of gel
      is produced on silver staining. Though different protocols of silver staining
      exist, the method described here is easy, cheap, reliable, and very sensitive.

PMID- 30097949
TI  - Heat/Pressure Treatment with Detergents Significantly Increases Curcumin
      Solubility and Stability: Its Use as an Environment-Friendly Protein Gel Stain.
AB  - Curcumin, the principal curcuminoid in the food spice turmeric, is insoluble in
      water at room temperature. We have previously solubilized curcumin in water with
      the application of heat (100  degrees C) and found that this solubilized curcumin
      could be used as a gel protein stain. However, heat solubilization in water
      solubilized only a small fraction of the curcuminoid (1.5%), making it relatively
      expensive to stain one gel ($1.5-2 per gel). Heat/pressure solubilization (121 
      degrees C/15 psi) helps increase the solubility of curcumin in water to only 5%.
      Therefore, we ventured into increasing curcumin solubility further by using
      detergents (Tween 20, Tween 80, or Triton X-100) combined with heat/pressure
      treatment. Curcumin solubilized with Tween 20, Tween 80 or Triton X-100 stained
      proteins efficiently as before. We could dramatically increase the solubility of
      curcumin by solubilizing in detergents such that we had to dilute the solubilized
      curcumin 1:100 with water to stain proteins. However, we had to use the soluble
      curcumin (extracted with heat/pressure alone) straight without dilution. Thus,
      the amount of curcumin solubilized with detergents was at least 100-fold, with
      0.5% Tween 80 being the most efficient. Staining can be carried out in 30 min,
      and sensitivity of staining is similar or better than that obtained with
      Coomassie Brilliant Blue (CBB). It is unnecessary to destain the gel, and excess
      curcumin can be discarded into the sink, unlike CBB. Curcumin solubilized in
      Tween 20 has been found to be stable for a period of over 4 years. Therefore,
      curcumin solubilized in Tween 80 or Triton X-100 can serve as an efficient
      nontoxic and environment-friendly protein stain. Tween 80 has been used in cough
      syrups to make a colloidal suspension, and also in foods. Solubilizing curcumin
      with Tween 80 would be a useful alternative to increase curcumin bioavailability
      in clinical studies.

PMID- 30097950
TI  - Fungal Laccase Efficiently Destains Coomassie Brilliant Blue-R-250 Stained
      Polyacrylamide Gels.
AB  - Fungal laccase-mediated destaining of Coomassie Brilliant Blue-R-250 stained
      polyacrylamide electrophoretic gel is very sensitive and environment friendly.
      Fermenting of Cerrena sp. HYB07 yields a broth with laccase activity which when
      supplemented with distilled water and used as a destaining solution results in a
      clear gel background in 2 h at 37  degrees C. Also, separation of the laccase
      enzyme for efficient functioning is not required. The method utilizes gel
      destaining and process of decolorizing dye simultaneously with a detection
      sensitivity of up to 10 ng. This technique avoids the use of hazardous organic
      compounds, as the destaining solution and the destain solution could be discarded
      easily without any further treatment.

PMID- 30097951
TI  - Destaining Coomassie Brilliant Blue-Stained Sodium Dodecyl Sulfate-Polyacrylamide
      Protein Gels Using a Household Detergent.
AB  - We report here a one-step method using the household detergent Vim Ultra to
      destain sodium dodecyl sulfate-polyacrylamide protein gels stained with Coomassie
      Brilliant Blue. This method, originally described by Pal and group, uses a 5%
      suspension of the detergent to destain gels efficiently. This method is cheap and
      user-friendly compared to the commonly used methanol-acetic acid-water containing
      destaining solvent.

PMID- 30097952
TI  - Paper Adsorbents Remove Coomassie Blue from Gel Destain and Used Gel Stain in an
      Environment-Friendly Manner.
AB  - Coomassie Brilliant Blue (CBB), used to stain protein gels, is known to be toxic.
      Therefore, laboratories do not discard used CBB into the sink owing to the
      possibility of it contaminating drinking water supplies. We tested the ability of
      various paper adsorbents to adsorb CBB released from gels during destaining. The
      efficiency was as follows-Kimwipes > Teri towels > multifold towels > Whatman
      numbers 1 and 3 filter papers. Addition of three Kimwipes during destaining
      helped adsorb the dye released from a CBB-stained mini-gel. Stain removal with
      Kimwipes helps reduce destain use, organic waste accumulation, enable recycling
      of nonradioactive destaining solution and is 7.5-fold cheaper than an available
      method for CBB disposal. Next, we used Kimwipes to deplete the dye from a used
      CBB staining solution awaiting proper disposal by our Institutional Safety
      Office. Seventy five Kimwipes successfully helped remove the dye from a 0.05% CBB
      staining solution in 5-10 min. The blue Kimwipes did not release the CBB stain
      even when squeezed dry after incubation in various salts, water, or acid
      solutions for 5 weeks. The CBB removed thus can be simply disposed of as solid
      waste and will not leach out from solid landfills. Kimwipes, thus, enables CBB
      disposal in an environmentally friendly manner and allows for recycling of
      destaining solution.

PMID- 30097953
TI  - Gel Drying Methods.
AB  - There are several reasons for drying of polyacrylamide gels after gel
      electrophoresis; for example, it is necessary if autoradiography has to be
      performed using radioactive labeled proteins. Another reason may be to simply
      store the gel in the laboratory book. Aside laborious commercial solutions, the
      simple and cheap drying protocol presented here may be sufficient especially for
      storage of the dried gel in the lab book.

PMID- 30097954
TI  - Stained Gels Can Be Stored for Several Months in Nonsealed Polyethylene Bags.
AB  - It is customary to dry gels (SDS-PAGE, native gels, or two-dimensional gels)
      after staining for record keeping purposes. This is typically carried out with
      gel dryers or by drying between two cellophane sheets held together by acrylic
      frames. Here, we report a simple method to store a variety of stained gels
      without any storage buffer within flexible nonsealed polyethylene bags. Gels can
      be stored for several months at room temperature without significant shrinking or
      protein diffusion. The gel stays hydrated owing to the de facto sealing achieved
      by the polyethylene sheets adhering air-tightly to the gel on either side. The
      microsaturated environment generated by the thin film of water molecules trapped
      between the gel and the polyethylene sheets, combined with the nonporous nature
      of the polyethylene sheets, apparently keeps the gel from cracking or shrinking
      significantly. The intensity of stained proteins increased during storage
      probably from the slight gel shrinkage observed. Storing gels in this manner is
      convenient (a) when low abundance protein spots from multiple two-dimensional
      electrophoresis gels have to be excised for in-gel tryptic digestion or
      electroelution and (b) for wet gel autoradiography. In addition to avoiding dryer
      contamination and saving drying time, these bags prevent the moist gel from
      sticking to X-ray film. Such storage could also prove useful for electrophoretic
      transfer of fixed and stained gels.

PMID- 30097955
TI  - Radiolabeling and Analysis of Labeled Proteins.
AB  - Protein-based preparations for biomedical research, and radiolabeled
      pharmaceuticals for nuclear medical diagnostics and therapy require highest
      chemical, radiochemical, and in particular protein purity. For detection of
      contaminations most commonly size exclusion high-performance liquid
      chromatography and polyacrylamide gel analysis in combination with silver
      staining is used. Here we describe a by far more sensitive radiolabeling method
      for the detection of traces of contaminating proteins.

PMID- 30097956
TI  - Using the variogram for vector outlier screening: application to feature-based
      image registration.
AB  - PURPOSE: Matching points that are derived from features or landmarks in image
      data is a key step in some medical imaging applications. Since most robust point
      matching algorithms claim to be able to deal with outliers, users may place high
      confidence in the matching result and use it without further examination.
      However, for tasks such as feature-based registration in image-guided
      neurosurgery, even a few mismatches, in the form of invalid displacement vectors,
      could cause serious consequences. As a result, having an effective tool by which
      operators can manually screen all matches for outliers could substantially
      benefit the outcome of those applications. METHODS: We introduce a novel
      variogram-based outlier screening method for vectors. The variogram is a powerful
      geostatistical tool for characterizing the spatial dependence of stochastic
      processes. Since the spatial correlation of invalid displacement vectors, which
      are considered as vector outliers, tends to behave differently than normal
      displacement vectors, they can be efficiently identified on the variogram.
      RESULTS: We validate the proposed method on 9 sets of clinically acquired
      ultrasound data. In the experiment, potential outliers are flagged on the
      variogram by one operator and further evaluated by 8 experienced medical imaging
      researchers. The matching quality of those potential outliers is approximately
      1.5 lower, on a scale from 1 (bad) to 5 (good), than valid displacement vectors.
      CONCLUSION: The variogram is a simple yet informative tool. While being used
      extensively in geostatistical analysis, it has not received enough attention in
      the medical imaging field. We believe there is a good deal of potential for
      clinically applying the proposed outlier screening method. By way of this paper,
      we also expect researchers to find variogram useful in other medical applications
      that involve motion vectors analyses.

PMID- 30097957
TI  - A patient-specific haptic drilling simulator based on virtual reality for dental
      implant surgery.
AB  - PURPOSE: In the dental implant surgery, there are inevitable risks due to the
      anatomically complex operation in the cranio-maxillofacial region. Therefore,
      there is a trend to use computer-aided technology to simulate the process of the
      implant surgery. In this study, we present a haptic simulator for trainees to
      study and rehearse the drilling performance of dental implant surgery. MATERIALS
      AND METHODS: The dental implant surgery simulator (DISS) is developed based on
      the haptic force-feedback device Omega.6, and some free open-source software
      libraries such as Computer Haptics and Active Interface (CHAI3D), Qt and
      Visualization Toolkit. To achieve the desired effects of drilling, the meshes are
      subdivided with a recursive algorithm which breaks down a triangular patch into 4
      sub-triangles. The drilling operation can be implemented at any specified
      location of the model. Once the drilling direction is determined, the position
      and rotation of the haptic device tool are constrained to the orientation through
      a dimension reduction algorithm. The driller diameter and drill speed are tunable
      to implement stepwise drilling for the patient-specific models. RESULTS: A
      patient-specific drilling simulator based on virtual reality for dental implant
      surgery is presented. The simulation of stepwise drilling was conducted, and
      three patient-specific models reconstructed by Computed Tomography data were
      employed to help the novices to find the suitable drilling parameter. CONCLUSION:
      The obtained results showed that the haptic-based DISS could simulate various
      dental implant surgeries with different driller diameter and drill speed which
      takes patient-specific models as input. The evaluation of the DISS proves its
      good performance and it could provide an effective method to improve the skills
      and experiences of trainees.

PMID- 30097958
TI  - Volumetric analysis of intracranial vessels: a novel tool for evaluation of
      cerebral vasospasm.
AB  - PURPOSE: Together with other diagnostic modalities, computed tomography
      angiography (CTA) is commonly used to indicate endovascular vasospasm treatment
      after subarachnoid hemorrhage (SAH), despite the fact that objective, user
      independent parameters for evaluation of CTA are lacking. This exploratory study
      was designed to investigate whether quantification of vasospasm by automated
      volumetric analysis of the middle cerebral artery M1 segment from CTA data could
      be used as an objective parameter to indicate endovascular vasospasm treatment.
      METHODS: We retrospectively identified SAH patients who underwent transcranial
      Doppler sonography (TCD), CTA, and CT perfusion (CTP), with or without subsequent
      endovascular treatment. We determined vessel volume/vessel length of the M1
      segments from CTA data and used receiver operating characteristic curve analysis
      to determine the optimal threshold of vessel volume to predict vasospasm
      requiring endovascular treatment. In addition, blinded investigators
      independently analyzed TCD, CTA, and CTP data. RESULTS: Of 45 CTA examinations
      with corresponding CTP and TCD examinations (24 SAH patients), nine indicated the
      need for endovascular vasospasm treatment during examination. In our patients,
      vessel volume < 5.8 uL/mm was moderately sensitive but fairly specific to detect
      vasospasm requiring endovascular treatment (sensitivity, 67%; specificity, 78%;
      negative predictive value (NPV), 89%; positive predictive value (PPV), 46%). For
      CTA, CTP, and TCD, we found NPVs of 96%, 92%, and 89%, PPVs of 40%, 35%, and 35%,
      sensitivities of 89%, 78%, and 67%, and specificities of 67%, 64%, and 69%,
      respectively. CONCLUSION: Vessel volumes could provide a new objective parameter
      for the interpretation of CTA data and could thereby improve multimodal
      assessment of vasospasm in SAH patients.

PMID- 30097959
TI  - Comparative analysis of membranous and other nephropathy subtypes and
      establishment of a diagnostic model.
AB  - This study aimed to compare clinical features between membranous nephropathy (MN)
      and nonmembranous nephropathy (non-MN), to explore the clinically differential
      diagnosis of these two types, and to establish a diagnostic model of MN. After
      renal biopsy was obtained, 798 patients were divided into two groups based on
      their examination results: primary MN group (n = 248) and non-MN group (n = 550).
      Their data were statistically analyzed. Logistic regression analysis indicated
      that anti-PLA2R antibodies, IgG, and Cr were independently correlated with MN,
      and these three parameters were then used to establish the MN diagnostic model. A
      receiver operating characteristic (ROC) curve confirmed that our diagnostic model
      could distinguish between patients with and without MN, and their corresponding
      sensitivity, specificity, and AUC were 79.9%, 89.4%, and 0.917, respectively. The
      cutoff value for this combination in MN diagnosis was 0.34. The established
      diagnostic model that combined multiple factors shows a potential for broad
      clinical applications in differentiating primary MN from other kidney diseases
      and provides reliable evidence supporting the feasibility of noninvasive
      diagnosis of kidney diseases.

PMID- 30097960
TI  - Classification and treatment of orbital venous malformations: an updated review.
AB  - Orbital venous malformation (OVM) is a congenital vascular disease. As a common
      type of vascular malformation in the orbit, OVM may result in vision
      deterioration and cosmetic defect. Classification of orbital vascular
      malformations, especially OVMs, is carried out on the basis of different
      categories, such as angiogenesis, hemodynamics, and locations. Management of OVM
      is complicated and challenging. Treatment approaches include sclerotherapy, laser
      therapy, embolization, surgical resection, and radiotherapy. A satisfactory
      outcome can be achieved only by selecting the appropriate treatment according to
      lesion characteristics and following the sequential multi-method treatment
      strategy. This article summarizes the current classification and treatment
      advances in OVM.

PMID- 30097963
TI  - Minimally Invasive Debridement for Infected Pancreatic Necrosis.
AB  - Necrotizing pancreatitis has historically been treated with open necrosectomy,
      which carries a high morbidity and mortality rate. More recently, there has been
      a shift towards endoscopic and percutaneous approaches employed as part of a
      minimally invasive step-up approach. Herein, we describe the technical approaches
      to video-assisted retroperitoneal debridement and sinus tract endoscopic
      debridement of pancreatic necrosis. Additionally, we review important patient
      selection considerations and the strengths and weaknesses of each of the
      approaches.

PMID- 30097961
TI  - RNA m6A modification and its function in diseases.
AB  - N6-methyladenosine (m6A) is the most common post-transcriptional RNA modification
      throughout the transcriptome, affecting fundamental aspects of RNA metabolism.
      m6A modification could be installed by m6A "writers" composed of core catalytic
      components (METTL3/METTL14/WTAP) and newly defined regulators and removed by m6A
      "erasers" (FTO and ALKBH5). The function of m6A is executed by m6A "readers" that
      bind to m6A directly (YTH domain-containing proteins, eIF3 and IGF2BPs) or
      indirectly (HNRNPA2B1). In the past few years, advances in m6A modulators
      ("writers," "erasers," and "readers") have remarkably renewed our understanding
      of the function and regulation of m6A in different cells under normal or disease
      conditions. However, the mechanism and the regulatory network of m6A are still
      largely unknown. Moreover, investigations of the m6A physiological roles in human
      diseases are limited. In this review, we summarize the recent advances in m6A
      research and highlight the functional relevance and importance of m6A
      modification in in vitro cell lines, in physiological contexts, and in cancers.

PMID- 30097964
TI  - Factors Associated with Long-Term Quality of Life After Restorative
      Proctocolectomy with Ileal Pouch Anal Anastomosis.
AB  - THE AIM: The aim of this study was to analyze factors associated with quality of
      life (QoL) after ileal pouch anal anastomosis (IPAA). METHODS: Patients who
      underwent IPAA (1983-2015) and replied to QoL questionnaire were identified from
      an IRB-approved prospectively maintained IPAA-database. QoL was assessed using
      Cleveland Global Quality of Life (CGQL) questionnaire at 1, 3, 5, and 10 years
      postoperatively. Patient cohort was divided in two groups: overall QoL score <=
      0.7 (low) and > 0.7 (high). Demographics, perioperative morbidity, and functional
      results were analyzed. RESULTS: A total of 4059 patients replied to the
      questionnaire at the most recent follow-up and were included. A total of 2889
      (71%) had overall QoL > 0.7 (group 1) and 1170 (29%) patients had overall QoL <=
      0.7 (group 2). Patients in group 1 had lower rates of early (44.6 vs. 50.4%, p =
      0.003) and late (55.7 vs. 64.5%, p < 0.003) postoperative complications. Kaplan
      Meier survival analysis demonstrated significantly higher rates of pouch failure
      among patients with lower QoL. Pouchitis, obstruction, fistulas, higher number of
      stools, and IPAA performed during the most recent decade (2005-2015) were
      significantly associated with lower QoL (<= 0.7), while S-pouch configuration was
      associated with higher QoL (> 0.7). CONCLUSION: Patient's characteristics and
      minimal perioperative complications impact patient's QoL following IPAA not only
      in the short term, but also in the long term.

PMID- 30097965
TI  - Evaluating Surgeons on Intraoperative Disposable Supply Costs: Details Matter.
AB  - BACKGROUND: Cost report cards have demonstrated variation in intraoperative
      supply costs and may allow comparisons between surgeons. However, cost data are
      complex and, if not properly vetted, may be inaccurate. METHODS: A retrospective
      assessment of intraoperative supply costs for consecutive laparoscopic
      cholecystectomies (2013-2017) at a 4-facility academic center was performed.
      Using unadjusted data (akin to an auto-generated report card), surgeons were
      ranked and highest to lowest-cost ratios were calculated. Then, four stepwise
      adjustments were performed: (1) excluded non-comparable operations and low volume
      (< 10 cases) surgeons, (2) eliminated outlier cases based on instrument profiles,
      (3) stratified by facility, and (4) adjusted prices (assigned one price;
      corrected aberrant/missing prices). Surgeon rank and highest to lowest-cost
      ratios were then re-calculated. RESULTS: The unadjusted data identified 1392
      cases for 33 surgeons (range, 1-317 cases). The ratio between the highest cost
      and lowest cost surgeon was 4.13. Steps 1 and 2 excluded 272 cases and 15
      surgeons. Facility sample sizes ranged from 144 to 621 (step 3). Adjusting prices
      (step 4) required manual review of 472 unique items: 45% had > 1 price and 16 had
      missing prices. After all adjustments, surgeons had different rankings and
      highest to lowest-cost ratios within sites were smaller (ratio range, 1.17-2.10).
      CONCLUSIONS: Evaluating surgeons based on intraoperative supply costs is
      sensitive to analytic methods. Surgeons who were initially considered cost
      outliers became the least expensive within a given site. Auto-generated cost
      report cards may require additional analyses to produce accurate comparative
      assessments.

PMID- 30097966
TI  - Presentation and Survival of Gastric Cancer Patients at an Urban Academic Safety
      Net Hospital.
AB  - INTRODUCTION: Gastric cancer is decreasing nationally but remains pervasive
      globally. We evaluated our experience with gastric cancer at a safety-net
      hospital with a substantial immigrant population. METHODS: Demographics,
      pathology, and treatment were analyzed for gastric adenocarcinoma at our
      institution (2004-2017). Chi-square analyses were performed for dependence of
      staging on demographics. Survival was evaluated with Kaplan-Meier and Cox
      regression analyses. RESULTS: We identified 249 patients (median age 65 years).
      Patients were predominantly born outside the USA or Canada (74.3%), non-white
      (70.7%), and federally insured (71.4%), and presented with late-stage disease
      (52.2%). Hispanic ethnicity, Central American birthplace, Medicaid insurance, and
      zip code poverty > 20% were associated with late-stage presentation (all p <
      0.05). Univariate analyses showed decreased survival for patients with late-stage
      disease, highest zip code poverty, and age >= 65 (all p < 0.05). On multivariate
      analysis, survival was negatively associated with late-stage presentation (HR
      4.45, p < 0.001), age >= 65 (1.80, p = 0.018), and H. pylori infection (2.02, p =
      0.036). CONCLUSION: Hispanic ethnicity, Central American birthplace, Medicaid
      insurance, and increased neighborhood poverty were associated with late-stage
      presentation of gastric cancer with poor outcomes. Further study of these
      populations may lead to screening protocols in order to increase earlier
      detection and improve survival.

PMID- 30097962
TI  - Complex interplay between tumor microenvironment and cancer therapy.
AB  - Tumor microenvironment (TME) is comprised of cellular and non-cellular components
      that exist within and around the tumor mass. The TME is highly dynamic and its
      importance in different stages of cancer progression has been well recognized. A
      growing body of evidence suggests that TME also plays pivotal roles in cancer
      treatment responses. TME is significantly remodeled upon cancer therapies, and
      such change either enhances the responses or induces drug resistance. Given the
      importance of TME in tumor progression and therapy resistance, strategies that
      remodel TME to improve therapeutic responses are under developing. In this
      review, we provide an overview of the essential components in TME and the
      remodeling of TME in response to anti-cancer treatments. We also summarize the
      strategies that aim to enhance therapeutic efficacy by modulating TME.

PMID- 30097967
TI  - Clinical Feasibility of Large Gastrotomy Closure Using a Flexible Tissue Glue
      Based on N-Butyl-2-Cyanoacrylate: Experimental Study in Pigs.
AB  - BACKGROUND: The use of synthetic adhesives such as cyanoacrylates has been
      established previously for a wide range of clinical indications. However, more
      research is necessary to evaluate their use in digestive closures or anastomosis.
      New chemical formulations developed to achieve more flexibility of synthetic
      adhesives (i.e., based on n-butyl-2-cyanoacrylate) could be an alternative to
      achieve this purpose. The aim of this study was to investigate the feasibility of
      using flexible cyanoacrylate adhesives for large gastric incision closure in an
      animal model. METHODS: Twelve farm pigs were divided in two groups depending on
      the type of closure method applied. In all cases, extra-large seven centimeters
      gastrostomies were performed. Braided absorbable hand-sewn interrupted suture
      versus n-butyl-2-cyanoacrylate with softener closure were compared during a 3
      week follow-up period. Histopathological aspects, hematologic and inflammatory
      biomarkers, and endoluminal pressure tolerated until leakage were assessed. The
      time spent on both closing procedures was compared. RESULTS: No differences
      between the two groups were found in any of the histopathological and
      inflammatory variables evaluated. The glued group tolerated a significantly
      higher pressure than the manual suture group. A reduction of surgery time was
      also observed. CONCLUSIONS: Our results suggest that flexible cyanoacrylates
      could be a feasible alternative to improve the clinical outcome of the closure of
      hollow viscera through more efficient sutureless procedures.

PMID- 30097969
TI  - Functional Assays of Stem Cell Properties Derived from Different Niches.
AB  - It has been described that adult tissues contain mesenchymal stem cell
      populations. The specific areas where stem cells reside are known as niches.
      Crosstalk between cells and their niche is essential to maintain the correct
      functionality of stem cell. MSCs present a set of abilities such as migration,
      invasion, and angiogenic potentials, which make them ideal candidates for cell
      based therapies. In order to test the regenerative capacity of these cells, we
      have described a methodology for the collection and for the evaluation of these
      mesenchymal precursors from different niches.

PMID- 30097970
TI  - Laparoscopic lavage and drainage for Hinchey III diverticulitis: review of
      technical aspects.
AB  - The surgical treatment for patients with generalized peritonitis complicating
      sigmoid diverticulitis is currently debated; particularly in case of diffuse
      purulent contamination (Hinchey 3). Laparoscopic lavage and drainage (LLD) has
      been proposed by some authors as a safe and effective alternative to single- or
      multi-stage resective surgery. However, among all the different studies on LLD,
      there is no uniformity in terms of surgical technique adopted and data show
      significant differences in postoperative outcomes. Aim of this review was to
      analyze the differences and similarities among the authors in terms of
      application, surgical technique and outcomes of LLD in Hinchey 3 patients. A
      bibliographical research was performed by referring to PubMed and Cochrane.
      "Purulent peritonitis", "Hinchey 3 diverticulitis", "acute diverticulitis",
      "colonic perforation" and "complicated diverticulitis" were used as key words.
      Twenty-eight papers were selected, excluding meta-analysis, reviews and case
      reports with a very small number of patients. The aim of this review was to
      establish how LLD should be done, suggesting important technical tricks. We found
      agreement in terms of indications, preoperative management, ports' positioning,
      antibiotics, enteral feeding and drain management. On the contrast, different
      statements regarding indications, adhesiolysis and management of colonic hole and
      failure of laparoscopic lavage are reported. A widespread diffusion of LLD and
      standardization of its technique are impossible because of data heterogeneity and
      selection bias in the limited RCTs. It is necessary to wait for long terms
      results from randomized clinical trials (RCTs) in progress to establish the
      efficacy and safety of this technique. More importantly, an increased number of
      highly skilled and dedicated colorectal laparoscopic surgeons are required to
      standardized the procedure.

PMID- 30097968
TI  - Technical Aspects of Orthotopic Liver Transplantation-a Survey-Based Study Within
      the Eurotransplant, Swisstransplant, Scandiatransplant, and British
      Transplantation Society Networks.
AB  - BACKGROUND: Orthotopic liver transplantation (OLT) has emerged as the mainstay of
      treatment for end-stage liver disease. However, technical aspects of OLT are
      still subject of ongoing debate and are widely based on personal experience and
      local institutional protocols. METHODS: An international online survey was sent
      out to all liver transplant centers (n = 52) within the Eurotransplant,
      Swisstransplant, Scandiatransplant, and British Transplant Society networks. The
      survey sought information on center-specific OLT caseload, vascular and biliary
      reconstruction, graft reperfusion, intraoperative control of hemodynamics, and
      drain policies. RESULTS: Forty-two centers gave a valid response (81%). Out of
      these, 50% reported piggy-back and 40.5% total caval replacement as their
      standard technique. While 48% of all centers generally do not apply veno-venous
      bypass (vvBP) or temporary portocaval shunt (PCS) during OLT, vvBP/PCS are
      routinely used in six centers (14%). Portal vein first reperfusion is used in
      64%, followed by simultaneous (17%), and retrograde reperfusion (12%). End-to-end
      duct-to-duct anastomosis without biliary drain (67%) is the most frequently
      performed method of biliary reconstruction. No significant associations were
      found between the center caseload and the surgical approach used. The predominant
      part of the centers (88%) stated that techniques of OLT are not evidence-based
      and 98% would participate in multicenter clinical trials on these topics.
      CONCLUSION: Technical aspects of OLT vary widely among European centers. The
      extent to which center-specific variation of techniques affect transplant
      outcomes in Europe should be elucidated further in prospective multicenter
      trials.

PMID- 30097971
TI  - Contribution of quantitative viral markers to document hepatitis B virus
      compartmentalization in cerebrospinal fluid during hepatitis B with neuropathies.
AB  - Extrahepatic manifestations linked to hepatitis B Virus (HBV) are usually
      indirect consequences of immune-mediated mechanisms triggered by the virus
      replication. Strong evidence of brain HBV replication is missing and direct
      involvement of HBV in nervous system symptoms has been rarely reported. We report
      two cases of neurological manifestations contemporary to HBV infection. In both
      cases, HBV-DNA and HBsAg could be quantified in the cerebrospinal fluid (CSF) at
      relatively high levels. Differential quantification of HBsAg and HBV viral load
      both in CSF and in blood as well as phylogenic studies on HBV genomic sequences
      obtained from blood and CSF provided strong arguments for central nervous system
      viral replication in both cases. Direct causality of HBV replication in the
      central nervous system in these clinical situations is certainly not demonstrated
      but these findings could expand the list of hepatitis viruses possibly involved
      in neurological disorders. Further studies should be promoted to better document
      possible HBV replication in the brain tissues and its consequences.

PMID- 30097972
TI  - Disambiguation of Isomeric Procyanidins with Cyclic B-Type and Non-cyclic A-Type
      Structures from Wine and Peanut Skin with HPLC-HDX-HRMS/MS.
AB  - Hydrogen/deuterium exchange coupled with high-resolution mass spectrometry was
      successfully applied for the identification of A-type tetrameric, pentameric, and
      hexameric procyanidins in peanut skin. This extended a previous study on isomeric
      cyclic B-type unconventional tetramer, pentamer, and hexamer procyanidins found
      in wine and cranberries. Not only had the method successfully identified the
      procyanidins with a single A-linkage (e.g., tetrameric m/z 1153.2608) by means of
      distinguishing them from their isomeric cyclic B-type analogues, but this method
      also worked for procyanidins with two or more A-linkages (such as the tetrameric
      m/z 1151.2452). As a further consequence, B-type cyclic pentamers and hexamers in
      wine have been elucidated with hydrogen/deuterium exchange (HDX) for the first
      time. Graphical Abstract ?.

PMID- 30097973
TI  - Synthesis, Characterization and Luminescent Properties of Anthracen- or Pyrene
      Based Coumarin Derivatives.
AB  - Three anthracen- or pyrene-based coumarin derivatives have been successfully
      synthesized and characterized by EA, IR and 1H NMR. The photophysical properties
      of all derivatives were investigated by UV-Vis and photoluminescence
      spectroscopic analysis. Their thermal stabilities were demonstrated by TGA. These
      compounds exhibit strong blue mission under ultraviolet light excitation and have
      potential possible to explore organic electroluminescent materials. The vacuum
      processed doped devices with a configuration of ITO/TAPC (20 nm)/TBADN: b1 (x
      wt%, 30 nm)/TPBi (50 nm)/Liq (2 nm)/Al (150 nm) was fabricated, in which the
      devices based on b1 exhibited the best electroluminescence performance with a
      maximum brightness of 8165 cd/m2 and a maximum luminous efficiencies of 6.13 cd/A
      and a maximum external quantum efficiency (EQE) of 2.75%.

PMID- 30097975
TI  - I know that "Kiki" is angular: The metacognition underlying sound-shape
      correspondences.
AB  - We examined the ability of people to evaluate their confidence when making
      perceptual judgments concerning a classic crossmodal correspondence, the
      Bouba/Kiki effect: People typically match the "Bouba" sound to more rounded
      patterns and match the "Kiki" sound to more angular patterns instead. For each
      visual pattern, individual participants were more confident about their own
      matching judgments when they happened to fall in line with the consensual
      response regarding whether the pattern was rated as "Bouba" or "Kiki". Logit
      regression analyses demonstrated that participants' confidence ratings and
      matching judgments were predictable by similar regression functions. This implies
      that the consensus and confidence underlying the Bouba/Kiki effect are
      underpinned by a common process, whereby perceptual features in the patterns are
      extracted and then used to match the sound according to rules of crossmodal
      correspondences. Combining both matching and confidence measures potentially
      allows one to explore and quantify the strength of associations in human
      knowledge.

PMID- 30097974
TI  - Papain Loaded Poly(epsilon-Caprolactone) Nanoparticles: In-silico and In-Vitro
      Studies.
AB  - Papain is a protease enzyme with therapeutic properties that are very valuable
      for medical applications. Poly(epsilon-caprolactone) (PCL) is an ideal polymeric
      carrier for controlled drug delivery systems due to its low biodegradability and
      its high biocompatibility. In this study, the three-dimensional structure and
      action mechanism of papain were investigated by in vitro and in silico
      experiments using molecular dynamics (MD) and molecular docking methods to
      elucidate biological functions. The results showed that the size of papain-loaded
      PCL nanoparticles (NPs) and the polydispersity index (PDI) of the NPs were 242.9
      nm and 0.074, respectively. The encapsulation efficiency and loading efficiency
      were 80.4 and 27.2%, respectively. Human embryonic kidney cells (HEK-293) were
      used for determining the cytotoxicity of papain-loaded PCL and PCL nanoparticles.
      The in vitro cell culture showed that nanoparticles are not toxic at low
      concentrations, while toxicity slightly increases at high concentrations. In
      silico studies, which were carried out with MD simulations and ADME analysis
      showed that the strong hydrogen bonds between the ligand and the papain provide
      stability and indicate the regions in which the interactions occur.

PMID- 30097976
TI  - How Do Gender Differences in Quality of Care Vary Across Medicare Advantage
      Plans?
AB  - BACKGROUND: Healthcare Effectiveness Data and Information Set (HEDIS) quality
      measures have long been used to compare care across health plans and to study
      racial/ethnic and socioeconomic disparities among Medicare Advantage (MA)
      beneficiaries. However, possible gender differences in seniors' quality of care
      have received less attention. OBJECTIVE: To test for the presence and nature of
      any gender differences in quality of care across MA Plans, overall and by domain;
      to identify those most at risk of poor care. DESIGN: Cross-sectional analysis of
      individual-level HEDIS measure scores from 23.8 million records using binomial
      mixed-effect models to estimate the effect of gender on performance. For each
      measure, we assess variation in gender gaps and their correlation with plan
      performance. PARTICIPANTS: Beneficiaries from 456 MA plans in 2011-2012 HEDIS
      data. MAIN MEASURES: Performance on 32 of 34 HEDIS measures which were available
      in both measurement years. The two excluded measures had mean performance scores
      below 10%. KEY RESULTS: Women experienced better quality of care than men for
      22/32 measures, with most pertaining to screening or treatment. Men experienced
      better quality on nine measures, including four related to cardiovascular disease
      and three to potentially harmful drug-disease interactions. Plans varied
      substantially in the magnitude of gender gaps for 21/32 measures; in general, the
      gender gap in quality of care was least favorable to men in low-performing plans.
      CONCLUSIONS: Women generally experienced better quality of care than men.
      However, women experienced poorer care for cardiovascular disease-related
      intermediate outcomes and potentially harmful drug-disease interactions. Quality
      improvement may be especially important for men in low-performing plans and for
      cardiovascular-related care and drug-disease interactions for women. Gender
      stratified reporting could reveal gender gaps, identify plans for which care
      varies by gender, and motivate efforts to address faults and close the gaps in
      the delivery system.

PMID- 30097977
TI  - Engaging High-Need Patients in Intensive Outpatient Programs: A Qualitative
      Synthesis of Engagement Strategies.
AB  - BACKGROUND: Intensive outpatient programs address the complex medical, social,
      and behavioral needs of individuals who account for disproportionate healthcare
      costs. Despite their promise, the impact of these programs is often diminished
      due to patient engagement challenges (i.e., low rates of patient participation
      and partnership in care). OBJECTIVE: The objective of this study was to identify
      intensive outpatient program features and strategies that increase high-need
      patient engagement in these programs. DESIGN: Qualitative study. PARTICIPANTS:
      Twenty program leaders and clinicians from 12 intensive outpatient programs in
      academic, county, Veterans Affairs, community, and private healthcare settings.
      APPROACH: A questionnaire and semi-structured interviews were used to identify
      common barriers to patient engagement in intensive outpatient programs and
      strategies employed by programs to address these challenges. We used content
      analysis methods to code patient engagement barriers and strategies and to
      identify program features that facilitate patient engagement. KEY RESULTS: The
      most common barriers to patient engagement in intensive outpatient programs
      included physical symptoms/limitations, mental illness, care fragmentation across
      providers and services, isolation/lack of social support, financial insecurity,
      and poor social and neighborhood conditions. Patient engagement strategies
      included concrete services to support communication and use of recommended
      services, activities to foster patient trust and relationships with program
      staff, and counseling to build insight and problem-solving capabilities. Program
      features that were identified as enhancing engagement efforts included: 1)
      multidisciplinary teams with diverse skills, knowledge, and personalities to
      facilitate relationship building; 2) adequate staffing and resources to handle
      the demands of high-need patients; and 3) a philosophy that permitted flexibility
      and patient-centeredness. CONCLUSIONS: Promising clinical, interpersonal, and
      population-based approaches to engaging high-need patients frequently deviate
      from standard practice and require creative and proactive staff with adequate
      time, resources, and flexibility to address patients' needs on patients' terms.

PMID- 30097979
TI  - A Promising New Noninvasive Measure of Cerebrovascular Reactivity: Not Yet
      Cerebral Autoregulation.

PMID- 30097978
TI  - Screening Positive for Cognitive Impairment: Impact on Healthcare Utilization and
      Provider Action in Primary and Specialty Care Practices.
AB  - BACKGROUND: Alzheimer's disease, the most common cause of dementia, goes
      unrecognized in half of patients presenting to healthcare providers and is
      associated with increased acute care utilization. Routine cognitive screening of
      older adults in healthcare settings could improve rates of dementia diagnosis and
      patterns of healthcare utilization. OBJECTIVE: To evaluate the impact of
      screening positive for cognitive impairment on provider action in primary and
      specialty care practices and patient healthcare utilization. DESIGN: Individuals
      asymptomatic for cognitive impairment completed cognitive screening with the Mini
      Cog (MC). Outcomes included MC screen-positive rates, provider follow-up actions,
      and healthcare utilization for all participants over a period of 36 months (18
      months prior to and following MC screening). Data were extracted from the
      electronic medical record (EMR). Healthcare provider interventions and healthcare
      utilization for screen-positive and -negative groups, before and after screening,
      were compared. PARTICIPANTS: Primary and specialty care patients (n = 787) aged
      >= 65 without history of cognitive impairment seen in HealthPartners, an
      integrated healthcare system in Minnesota and Western Wisconsin. KEY RESULTS: In
      primary care and neurology practices combined, over the entire 36-month study
      window, individuals screening positive showed 32% higher rates of ED visits (p <
      0.05) pre and post-screening compared to those screening negative. Screen
      positive also showed 39% higher rates of hospitalizations pre-screening (p <
      0.05) and 58% higher rates post-screening (p < 0.01). While screen-detected
      cognitive impairment was associated with some relevant provider follow-up action
      in 32% of individuals, subsequent healthcare utilization did not change between
      the 18-month pre- and post-screening periods. CONCLUSION: Despite being
      associated with higher rates of healthcare utilization, screening positive on the
      MC led to a change in provider action in a minority of cases and did not reduce
      post-screening healthcare utilization. Screening for cognitive impairment alone
      is not sufficient to alter patterns of provider practice or patient healthcare
      utilization.

PMID- 30097980
TI  - Safety, Feasibility, and Efficiency of a New Cooling Device Using Intravenous
      Cold Infusions for Fever Control.
AB  - BACKGROUND: Fever control plays a key role in therapy of patients with acute
      brain injury. The infusion of cold saline could serve as an alternative or
      additional method for targeted temperature management. However, it is difficult
      to estimate the amount of fluid required to achieve normothermia merely on the
      basis of body weight. There is no standardized load management regarding the
      administration of cold saline, and no closed-loop systems based on continuous
      temperature-controlled feedback are available. The primary purpose of the present
      study was to evaluate the feasibility, efficacy, and safety of a new automated
      fluid infusion system. METHODS: Twelve patients with acute brain injury and
      febrile episodes were treated with the automated infusion device tempedy
      (seiratherm GmbH, Herzogenaurach, Germany). Patients were included if bladder
      temperature still was >= 37.9  degrees C after administration of antipyretic
      medication, cold washing solutions, and ice packs more than 2 h earlier. The
      efficacy was examined by measuring the time and amount of fluid needed to reach
      and maintain target temperature. Feasibility and safety were assessed based on
      recording any technical difficulties with the new device and the occurrence of
      clinical signs of fluid overload such as acute pulmonary edema, electrolyte
      disturbances, or acid-base dysfunction. RESULTS: The mean time was 73 min (range
      from 15 to 330 min) and 1650 ml the mean amount of fluid (21.2 ml/kg; SD 28.5
      ml/kg) to reach the target temperature. The mean total fluid balance to reach and
      maintain the target temperature in the first 12 h was 1350 ml (SD 1550 ml). In
      the first 12 h 89.4% of the time temperature values were in the target range
      (median 95.3%, range 83.8-10%). No clinical signs of fluid overload such as an
      acute pulmonary edema or device-related adverse events occurred. CONCLUSION:
      Target temperature management with the new automated infusion device is feasible.
      Although we provided first data regarding safety, further controlled randomized
      studies are needed to evaluate the long-time safety, as well as the best
      indications and timing for this cooling device.

PMID- 30097981
TI  - Response to Dr. Frederick Adam Zeiler.

PMID- 30097982
TI  - Evaluation of Essential and Toxic Elements in Amniotic Fluid and Maternal Serum
      at Birth.
AB  - The objective of this study was to determine the concentration and the reference
      ranges of essential and toxic elements in amniotic fluid (AF) and maternal serum
      (MS) at birth. This study was conducted among 175 healthy pregnant Caucasian
      European women aged 18-42. AF and maternal blood samples were collected during
      delivery. An inductively coupled plasma mass spectrometry (ICP-MS) technique was
      used to determine the levels of Mg, Co, Cu, Zn, Sr, Cd, Ba, Pb, U, Ca, Cr, Al,
      Mn, V, Fe, As, Se and Sb in AF and MS. The range of reference values was
      calculated for all analyzed elements in the serum and AF. The mean concentrations
      of elements, except Pb, were generally higher in MS than in AF. Multiple
      regression analysis showed that the maternal/newborn body mass (MBM/NBM) ratio
      was a strong negative predictor (among maternal age and gravidity) of Mg
      concentration in amniotic fluid. In the serum, MBN/NBM ratio was a strong
      positive predictor of Cu concentration. Moreover, regression analysis showed that
      maternal age was an independent positive predictor of the Se level in maternal
      serum. The reference value ranges of 18 essential and toxic elements were
      established in AF and MS among a population of healthy pregnant Polish women at
      delivery. The level of Mg, Co, Cu, Ca and Se in AF and MS can be determined by
      maternal age and MBM/NBM ratio. These results can be useful in counseling
      individuals with pregnancies affected by exposure to one of the parameters under
      investigation.

PMID- 30097983
TI  - Mineral Composition of Amazonian Fruits by Flame Atomic Absorption Spectrometry
      Using Multivariate Analysis.
AB  - This study aimed to evaluate the mineral composition in native and non-native
      Amazonian fruits using flame atomic absorption spectrometry (FAAS) and
      multivariate methods, such as principal component analysis (PCA) and hierarchical
      cluster analysis (HCA), in order to conduct a more thorough evaluation of the
      original data. The accuracy was checked by certified reference material analysis
      (Poplar leaves) and spike experiments. The results of the analysis were in
      agreement with the certified values, with analytical recoveries for all analytes
      in an acceptable range from 82 to 113%, and relative standard deviations (RSD)
      were in the range of 0.2-18%. Furthermore, PCA explained 68% of the total
      variance, while HCA confirmed the correlations found in the PCA, allowing for the
      evaluation of the degree of similarity between the fruits studied. These results
      will be used to better understand the distribution of inorganic constituents
      within these Amazonian fruits.

PMID- 30097984
TI  - Coastal erosion-a "new" land-based source of labile mercury to the marine
      environment.
AB  - Mercury (Hg) can be introduced into the marine environment in many different
      ways. In the case of the Baltic Sea, rivers and atmospheric deposition are the
      predominant ones. However, in the face of ongoing climate change, a new potential
      source, coastal erosion, is starting to become more important and is currently
      considered to be the third largest source of Hg in the Gdansk Basin region. It is
      especially significant along sections of coastline where, due to the higher
      frequency of extreme natural phenomena such as storms, heavy rains, and floods,
      increased erosion processes have already been noted. Cliffs, which account for
      about 20% of the Polish coastline, are particularly vulnerable. The aim of the
      study was to estimate the annual load of labile Hg entering the Gdansk Basin as a
      result of coastal erosion. Samples of down-core sediments (0-65 cm) were
      collected in the years 2016-2017 from selected cliffs situated in the Gulf of
      Gdansk area. The thermodesorption method was used to distinguish between labile
      and stable fractions of Hg. Considering the mean total Hg concentrations in the
      collected sediments (9.7 ng g-1) and the mean share of labile (64%), bioavailable
      mercury, it was estimated that the load of labile Hg originating from coastal
      erosion entering the Gdansk Basin is 10.0 kg per year. The load can increase by
      up to 50% in the case of episodic abrasion events during heavy storms and rains.

PMID- 30097985
TI  - Effect of amendments on contaminated soil of multiple heavy metals and
      accumulation of heavy metals in plants.
AB  - The contamination of soil with heavy metals is a severe problem due to adverse
      impact of heavy metals on environmental safety and human health. It is essential
      to remediate soil contaminated with heavy metals. This study has evaluated the
      effects of pine biochar, kaolin, and triple super phosphate (TSP) on multiple
      heavy metals (Ni, Zn, Cu, and Cd) in contaminated soil and accumulation of heavy
      metals in plants. The amendments can reduce availability of heavy metals in soil
      by increasing pH, adsorption, complexation, or co-precipitation. Different
      amendments have variable effects on accumulation of heavy metals in plants and in
      soil due to its diverse mechanism of stability. The results showed that
      application of triple super phosphate (TSP) has significant reduced soil Cd
      exchangeable (EXC) fraction from 58.59 to 21.30%. Bound to carbonates (CAR)
      fraction decreased from 9.84 to 5.11%, and bound to Fe-Mn oxides (OX) fraction
      increased from 29.61 to 69.86%. The triple super phosphate (TSP) has the ability
      to stabilize Cu and especially Cd. However, triple super phosphate (TSP) has
      enhanced ecological risk of Zn and Ni. Application of pine biochar has
      significantly enhanced soil pH. The kaolin has significantly reduced EXC fraction
      of Cd and increased OX fraction of Cu. The amendments and heavy metals have not
      caused significant effect on SPAD value of Buxus microphylla Siebold & Zucc (B.
      microphylla). The triple super phosphate (TSP) has significant decreased biomass
      of B. microphylla and bamboo-williow (Salix sp.) by 24.91 and 57.43%,
      respectively. Pine biochar and kaolin have increased the accumulation of Zn and
      Cd in plants. It is concluded that triple super phosphate (TSP) was effective in
      remediation of Cd and kaolin was effective in remediation of Cd and Cu. Pine
      biochar was effective in remediation of Cd, Cu, and Zn.

PMID- 30097986
TI  - Organic contaminants in the effluent of Chinese wastewater treatment plants.
AB  - The effluents of wastewater treatment plants (WWTPs) are the important sources
      for pollutants. These pollutants may entry into surface water, groundwater, and
      soil by recharging and irrigation then pose risk to human beings. Using reports
      from the past 20 years (n = 58), we conducted this review of organic contaminants
      (OCs) in the effluent of Chinese WWTPs. All the studies were during 2005 to 2017
      and more than two papers were conducted in every year. Nineteen provinces (20
      cities) were covered and most of the studies were located in the eastern part of
      China, especially the most developed and highest density of population areas. Two
      hundred eighty-four OCs were contained. E antibiotics, endocrine-disrupting
      chemicals (EDCs), and pharmaceuticals were the most commonly studied groups of
      OCs, and ofloxacin, norfloxacin, and sulfamethoxazole were the three most
      commonly reported OCs. The highest concentration appeared for bisphenol A (BPA).
      The relative standard deviations (RSDs) of concentrations of the most commonly
      studied compounds were high. In the future, more studies should pay attention on
      national analysis and more pollutants.

PMID- 30097987
TI  - Novel combined method of biosorption and chemical precipitation for recovery of
      Pb2+ from wastewater.
AB  - A novel combined biosorption-precipitation process has been designed and applied
      to recycle Pb2+ from low concentration lead containing wastewater. Pb2+ was
      firstly removed selectively from wastewater by pyromellitic dianhydride (PMDA)
      modified sugarcane bagasse (SB) fixed-bed column, and then, it was desorbed into
      the concentrated eluate and recycled by adding chemical precipitant. Adsorption
      performance of the column and optimum desorption and precipitation condition for
      Pb2+ were investigated in detail. Results showed that the as-prepared column
      could efficiently remove Pb2+ from aqueous solution and optimum condition for
      Pb2+ precipitation in eluate was at pH 3.0 and molar ratio of precipitant to Pb2+
      of 5:1 by using Na3PO4 as precipitant. Recovery experiment illustrated that Pb2+
      was selectively removed from wastewater containing ions of Pb2+, Zn2+, Cd2+,
      Ca2+, K+, and Na+ through competitive substitution adsorption on the modified SB,
      and mass ratio of the five metal ions in eluate was 96.8:0.7:0.7:0.7:0.5:0.5.
      Pb2+ in this concentrated and purified eluate solution was recycled efficiently
      by adding Na3PO4. The combined method had great potential in application of heavy
      metal recovery from wastewater.

PMID- 30097988
TI  - Efficacy and Safety of Topical Cantharidin Treatment for Molluscum Contagiosum
      and Warts: A Systematic Review.
AB  - BACKGROUND AND OBJECTIVE: Topical cantharidin is routinely used for the treatment
      of molluscum contagiosum and warts. The objective of this systematic review is to
      assess the efficacy and safety of topical cantharidin treatment for molluscum
      contagiosum and warts. METHODS: We performed a systematic review of studies
      assessing topical cantharidin treatment of molluscum contagiosum or warts. We
      searched the databases of Cochrane, EMBASE, GREAT, LILACS, MEDLINE, and Scopus.
      Two authors performed the study selection and data extraction. RESULTS: Twenty
      studies (1958-2018) met inclusion/exclusion criteria. Twelve studies assessed
      warts, and eight studies assessed molluscum contagiosum. Overall, 1752 patients
      were included (range 0.3-62 years; specified in 15 studies). Clearance rates with
      topical cantharidin for molluscum contagiosum were variable (range 15.4-100%).
      Significant clearance of warts with maintenance of clearance was demonstrated
      with topical cantharidin alone. Topical cantharidin in combination with
      podophyllotoxin and salicylic acid demonstrated efficacy for plantar warts
      (pediatric and adult; clearance rate range 81-100%; four studies had 100%
      clearance), with the majority clearing after a single treatment. Satisfaction
      with cantharidin therapy was high, especially in molluscum contagiosum. Pain (7
      85.7%), blistering (10-100%), and hyper-/hypopigmentation (1.8-53.3%) were the
      most commonly occurring adverse effects with cantharidin treatment. CONCLUSION:
      Topical cantharidin demonstrated clearance of warts, particularly in combination
      with podophyllotixin and salicylic acid, and modest benefit for pediatric
      molluscum contagiosum with good tolerability and safety.

PMID- 30097990
TI  - Training Future Leaders: Experience from China-ASEAN Cancer Control Training
      Program.
AB  - Cancer care professionals are pivotal in translating the knowledge into action in
      the continuum of cancer control process. Unfortunately, in China and the
      Association of South-east Asian Nations (ASEAN), limited training opportunities
      are available for health professionals in the area of cancer prevention and
      control. Therefore, the Cancer Hospital, Chinese Academy of Medical Sciences
      (CICAMS), and the International Agency for Research on Cancer (IARC)
      collaboratively designed and held the China-ASEAN Cancer Control and Prevention
      Training Program to provide continuing education opportunities for cancer
      professionals from China and ASEAN countries. The aim of this article is to
      report on the effectiveness and quality of the program and share our experience.
      A total of 36 participants from 12 countries completed the whole course including
      1-month online learning and 1-week face-to-face workshop and cancer control
      facility tour in October 2017. After completion of the program, all participants
      were invited to fill out a questionnaire and to provide their comments on the
      training course. Out of 36 participants, 33 completed the evaluation form and
      they rated the training course highly in terms of satisfaction, value, and
      likelihood of recommending it to other colleagues. Additionally, all participants
      provided very detailed and practical comments on the course. Such an intensive,
      short-term, and comprehensive training program is expected to help participants
      establish a broader view of cancer prevention and control within the wider health
      services and be involved in national cancer control programs in a more efficient
      way. This training course could serve as a model for other institutes dedicated
      to nurturing future leaders in cancer control.

PMID- 30097989
TI  - Subclinical Leishmania infection in patients with rheumatic diseases under
      biological drugs.
AB  - PURPOSE: Climate changes and immunosuppression are influencing the spread of
      leishmaniasis and re-emergence in Northern Italy, respectively. We evaluated the
      prevalence of subclinical leishmaniasis in patients from a Northern Italian
      region with chronic inflammatory rheumatism (CIRD) receiving biological drugs
      (BD) and correlated it to the area of residence. METHODS: DNA from PBMC of
      patients affected by CIRD treated with either BD for at least 5 years (Group A)
      or other immunosuppressive drugs (Group B) was investigated by a qPCR for
      Leishmania infantum kDNA and compared to healthy subjects (Group C). Variables
      such as sex and age, rural areas, dog ownership, type of BD administered and
      association between BD and steroids, were evaluated by statistical analysis.
      RESULTS: A higher proportion of L. infantum DNA positivity was found in Group A
      than in Group C (p < 0.05), while no parasite DNA was detected in Group B. In
      Group A, 18/50 patients (36%) had higher rates of parasite DNA (from 1 to 136 to
      1.000.000 copies/ml) than Group C (from 1 to 10 copies/ml). 14/18 (77.7%) of
      positive patients from Group A lived in rural areas, but no statistical
      differences occurred in relation to dog ownership or BD type (p < 0.0003).
      CONCLUSIONS: We can speculate that exposure to rural areas appears to be a factor
      closely linked with the risk of developing Leishmania subclinical infection. A
      screening with molecular methods in patients with CIRD treated with BD living in
      these areas and monitoring Leishmania DNA during such therapies, would be
      mandatory to prevent delay in diagnosis should VL symptoms appear.

PMID- 30097991
TI  - Lathosterolosis: A Relatively Mild Case with Cataracts and Learning Difficulties.
AB  - Lathosterolosis is a rare defect of cholesterol synthesis. Only four previous
      cases have been reported, two of whom were siblings. We report a fifth patient,
      with a relatively mild phenotype. He presented at 5 years of age with bilateral
      posterior cataracts, which were managed with lensectomies and intraocular lens
      implants. He also had learning difficulties, with a full-scale IQ of 64 at 11
      years of age. His head circumference is between the 0.4th and 2nd centiles, and
      he has mild hypotonia and subtle dysmorphism (a high-arched palate, anteverted
      nostrils, long philtrum and clinodactyly of toes). The diagnosis was established
      after sequencing a panel of genes associated with cataracts, which revealed
      compound heterozygous SC5D mutations: c.479C>G p.(Pro160Arg) and c.630C>A
      p.(Asp210Glu). The plasma lathosterol concentration was markedly raised at 219.8
      MUmol/L (control range 0.53-16.0), confirming the diagnosis. The c.630C>A
      p.(Asp210Glu) mutation has been reported in one previous patient, who also had a
      relatively mild phenotype (Ho et al., JIMD Rep 12:129-134, 2014). The mutation
      leads to a relatively conservative amino acid substitution, consistent with some
      residual enzyme activity. Our patient's family did not notice any benefit from
      treatment with simvastatin. In summary, milder patients with lathosterolosis may
      present with learning difficulties, cataracts and very subtle dysmorphism. The
      diagnosis will be missed unless plasma sterols are analysed or relevant genes
      sequenced.

PMID- 30097992
TI  - Cobalamin D Deficiency Identified Through Newborn Screening.
AB  - Cobalamin D deficiency (cblD) is one of the least common cobalamin metabolism
      disorders. It may result in isolated homocystinuria, isolated methylmalonic
      aciduria, or combined methylmalonic aciduria and homocystinuria (cblD-combined).
      Only seven cases of the combined cblD form have been reported to date. Due to the
      rarity of this disorder, the presentation and symptoms are not well described. We
      present an eighth case of the cblD-combined subtype, who had a positive newborn
      screen (NBS) on day of life 3. She was symptomatic and developed lethargy and
      poor oral intake at 8 days of life. She was treated with 10% dextrose, folinic
      acid, intramuscular hydroxocobalamin, and betaine. Despite the early initiation
      of treatment, she developed complications of the disease and was found to have
      abnormal brain imaging findings at 17 days of age and macular atrophy at 3 months
      of age and has global developmental delay. We provide detailed description of her
      presentation, her treatment, and her complications to aid in the understanding of
      this rare disorder, which is very similar to the more common cobalamin C disorder
      (cblC).

PMID- 30097993
TI  - Effect of Empagliflozin Versus Placebo on Cardiac Sympathetic Activity in Acute
      Myocardial Infarction Patients with Type 2 Diabetes Mellitus: Rationale.
AB  - INTRODUCTION: Protection from lethal ventricular arrhythmias leading to sudden
      cardiac death is one of the most important problems after myocardial infarction.
      Cardiac sympathetic hyperactivity is related to poor prognosis and fatal
      arrhythmias and can be non-invasively assessed with heart rate variability, heart
      rate turbulence, T-wave alternans, late potentials, and 123I-meta
      iodobenzylguanide (123I-MIBG) scintigraphy. Sodium glucose cotransporter 2
      (SGLT2) inhibitors potentially reduce sympathetic nervous system activity that is
      augmented in part due to the stimulatory effect of hyperglycemia. The EMBODY
      trial is designed to determine whether the suppression of cardiac sympathetic
      activity induced by the SGLT2 inhibitor is accompanied by protection against
      adverse cardiovascular outcomes. METHODS: The EMBODY trial is a prospective,
      multicenter, randomized, double-blind, placebo-controlled trial in patients with
      acute MI and type 2 diabetes in Japan. A total of 98 patients will be randomized
      (1:1) to receive once-daily placebo or empagliflozin, an SGLT2 inhibitor, 10 mg.
      The primary end point is the change from baseline to 24 weeks in heart rate
      variability. Secondary end points include the change from baseline for other
      sudden cardiac death surrogate-markers such as heart rate turbulence, T-wave
      alternans, late potentials, and 123I-MIBG scintigraphy imaging. Adverse effects
      will be evaluated throughout the trial period. PLANNED OUTCOMES: The EMBODY trial
      will evaluate the potential cardioprotective effect of empagliflozin and will
      provide additional important new data regarding its preventative effects on
      sudden cardiac death. TRIAL REGISTRATION: Unique Trial Number, UMIN000030158 (
      https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000034442 ).
      FUNDING: Nippon Boehringer Ingelheim and Eli Lilly and Company.

PMID- 30097994
TI  - Comorbidity Type and Health Care Costs in Type 2 Diabetes: A Retrospective Claims
      Database Analysis.
AB  - INTRODUCTION: Previous studies suggest that the type and combination of
      comorbidities may impact diabetes care, but their cost implications are less
      clear. This study characterized how diabetes patients' health care utilization
      and costs may vary according to comorbidity type classified on the basis of the
      Piette and Kerr framework. METHODS: We conducted a retrospective observational
      study of privately insured US adults newly diagnosed with type 2 diabetes (n =
      138,466) using the 2014-2016 Optum Clinformatics(r) Data Mart. Diabetes patients
      were classified into five mutually exclusive comorbidity groups: concordant only,
      discordant only, both concordant and discordant, any dominant, and none. We
      estimated average health care costs of each comorbidity group by using
      generalized linear models, adjusting for patient demographics, region, insurance
      type, and prior-year costs. RESULTS: Most type 2 diabetes patients had discordant
      conditions only (27%), dominant conditions (25%), or both concordant and
      discordant conditions (24%); 7% had concordant conditions only. In adjusted
      analyses, comorbidities were significantly associated with higher health care
      costs (p < 0.0001) and the magnitude of the association varied with comorbidity
      type. Diabetes patients with dominant comorbidities incurred substantially higher
      costs ($38,168) compared with individuals with both concordant and discordant
      conditions ($20,401), discordant conditions only ($9173), concordant conditions
      only ($9000), and no comorbidities ($3365). More than half of the total costs in
      our sample (53%) were attributable to 25% of diabetes patients who had dominant
      comorbidities. CONCLUSIONS: Diabetes patients with both concordant and discordant
      conditions and with clinically dominant conditions incurred substantially higher
      health costs than other diabetes patients. Our findings suggest that diabetes
      management programs must explicitly address concordant, discordant, and dominant
      conditions because patients may have distinctly different health care needs and
      utilization patterns depending on their comorbidity profiles. The Piette and Kerr
      framework may serve as a screening tool to identify high-need, high-cost diabetes
      patients and suggest targets for tailored interventions. FUNDING: Sanofi.

PMID- 30097995
TI  - Cost-Effectiveness of Insulin Degludec vs. Insulin Glargine U100 in Type 1 and
      Type 2 Diabetes Mellitus in a UK Setting.
AB  - BACKGROUND: Understanding which therapeutic innovations in diabetes represent the
      best value requires rigorous economic evaluation. Data from randomised controlled
      trials and observational studies indicate that insulin degludec has a
      hypoglycemia advantage versus insulin glargine 100 units/mL (glargine U100), the
      most widely prescribed basal insulin analogue in the UK. This analysis was done
      to more rigorously assess cost-effectiveness in a UK setting. METHODS: Data from
      two double-blinded, randomised, two-period crossover trials in type 1 (SWITCH 1)
      and type 2 (SWITCH 2) diabetes mellitus were used to assess the cost
      effectiveness of degludec vs. glargine U100 with an economic model. Cost
      effectiveness was analysed over a 1-year time horizon based on the different
      rates of hypoglycaemia and actual doses of insulin used, rather than glycaemic
      control due to the treat-to-target trial design. RESULTS: In type 1 diabetes
      mellitus, degludec was highly cost-effective compared with glargine U100, with an
      incremental cost-effectiveness ratio of L984 (increased costs of only L23/year
      and improvement in participant health of 0.0232 quality-adjusted life-years
      (QALYs)). In type 2 diabetes mellitus, it was estimated that quality of life was
      improved (0.0065 QALYs gain) with degludec compared with glargine U100 at an
      increased annual cost of L117 (incremental cost-effectiveness ratio, L17,939).
      One-way sensitivity analyses showed that the results were robust to changes in
      parameters in both type 1 and type 2 diabetes mellitus. CONCLUSIONS: The rigorous
      design of the SWITCH trials, coupled with a representative patient population and
      a definition of hypoglycaemia that is relevant for real-world patients, makes the
      results of these trials highly generalisable. The within-trial analysis has the
      added value of being able to include doses and event rates directly from the
      trials. This short-term economic analysis estimated that IDeg would be cost
      effective relative to IGlar U100 in both type 1 and type 2 diabetes mellitus in
      the UK. TRIAL REGISTRATION: SWITCH 1 (NCT02034513); SWITCH 2 (NCT02030600).
      FUNDING: Novo Nordisk, Soborg, Denmark.

PMID- 30097996
TI  - Effect of Age on Conversion to Everolimus with Calcineurin Inhibitor Minimization
      at A Late Post-Transplant Stage.
AB  - PURPOSE: The purpose of this study was to identify the risk factors for
      everolimus discontinuation in kidney transplant recipients converted to
      everolimus with calcineurin inhibitor (CNI) minimization at a late post
      transplant stage. MATERIALS AND METHODS: An observational retrospective cohort
      study was conducted on a total of 38 recipients of kidney transplantation at our
      institution from June 2012 to March 2015 who were converted from antimetabolites
      to everolimus at a late post-transplant stage and followed for 1 year. We divided
      the patients into two groups to evaluate the factors affecting everolimus
      discontinuation after conversion: everolimus continuation group (n = 23),
      patients in whom everolimus maintained, and everolimus discontinuation group (n =
      15), patients in whom everolimus were stopped within 1 year after conversion.
      RESULTS: Age at conversion was significantly older in the everolimus
      discontinuation group compared to the everolimus continuation group (57.9 +/-
      12.0 years in the everolimus discontinuation group vs 45.7 +/- 11.2 years in the
      everolimus continuous group; P = .0062). Multivariate cox proportional hazard
      regression analysis revealed that age at conversion significantly correlated with
      everolimus discontinuation (P = .012). Receiver operating characteristic curve of
      age at conversion showed that the cut-off value was 55 years old for the
      everolimus discontinuation group [area under curve 0.804, 95% confidence interval
      (0.654-0.954), sensitivity 86.7%, specificity 65.2%]. CONCLUSION: Our results
      indicated that late conversion to everolimus with CNI minimization in elderly
      recipients older than 55 years of age may be associated with more frequent
      adverse events and discontinuations.

PMID- 30097998
TI  - The application of stable-isotope tracers to study human musculoskeletal protein
      turnover: a tale of bag filling and bag enlargement.
AB  - The nutritional regulation of protein and amino acid balance in human skeletal
      muscle carried out by the authors with Mike Rennie is reviewed in the context of
      a simple physiological model for the regulation of the maintenance and growth of
      skeletal muscle, the "Bag Theory". Beginning in London in the late 1970s the work
      has involved the use of stable isotopes to probe muscle protein synthesis and
      breakdown with two basic experimental models, primed-dose continuous tracer
      infusions combined with muscle biopsies and arterio-venous (A-V) studies across a
      limb, most often the leg, allowing both protein synthesis and breakdown as well
      as net balance to be measured. In this way, over a 30 year period, the way in
      which amino acids and insulin mediate the anabolic effect of a meal has been
      elaborated in great detail confirming the original concepts of bag filling within
      the muscle endomysial "bag", which is limited by the "bag" size unless bag
      enlargement occurs requiring new collagen synthesis. Finally we briefly review
      some new developments involving 2 H2 O labelling of muscle proteins.

PMID- 30097999
TI  - DNA primase polypeptide 1 (PRIM1) involves in estrogen-induced breast cancer
      formation through activation of the G2/M cell cycle checkpoint.
AB  - The DNA primase polypeptide 1 (PRIM1) is responsible for synthesizing small RNA
      primers for Okazaki fragments generated during discontinuous DNA replication.
      PRIM1 mRNA expression levels in breast tumor samples were detected by real-time
      PCR analysis. Xenografted tumor model was established to study the carcinogenic
      role of PRIM1 and its potential therapeutic applications. The average PRIM1 mRNA
      (copy number * 103 /MUg) expression was 4.7-fold higher in tumors than in normal
      tissue (*p = 0.005, n = 254). PRIM1 was detected preferentially at a higher level
      (>40-fold) in poorly differentiated tumor tissues (n = 46) compared with more
      highly differentiated tumors tissues (n = 10) (*p = 0.005). Poor overall survival
      rate was correlated to the estrogen receptor positive (ER+, n = 20) patients with
      higher PRIM1 expression when compare to the ER- (n = 10) patients (Chi Square
      test, p = 0.03). Stable expression of PRIM1-siRNA in the ER+ BT-474 cells
      xenograft tumors significantly reduced tumor volume in SCID mice (*p = 0.005).
      The anti-tumoral effects of inotilone isolated from Phellinus linteus was tested
      and had significant effects on the inhibition of PRIM1 protein expression in ER+
      breast cancer cells. In vivo study was performed by administering inotilone (10
      mg/kg, twice a week for 6 weeks), which resulted in significantly reduced BT-474
      xenografted tumor growth volume compared with control (n =5 per group, *p <
      0.05). This study provides evidences for the prognostic effects of PRIM1 with
      poor overall survival rate in the ER+ patients and will be valuable to test for
      therapeutic purpose.

PMID- 30098000
TI  - Mechanistic insights of epithelial protein lost in neoplasm in prostate cancer
      metastasis.
AB  - EPLIN is frequently downregulated or lost in various cancers. The purpose of this
      study was to evaluate the importance of EPLIN in prostate cancer progression,
      with particular focus on the mechanistic implications to elucidate EPLIN's tumor
      suppressive function in cancer. EPLIN expression was evaluated in prostate cancer
      cell lines and tissues. PC-3 and LNCaP EPLINalpha overexpression models were
      generated through transfection with EPLINalpha sequence and EPLIN knockdown was
      achieved using shRNA in CA-HPV-10 cells. Functional assays were performed to
      evaluate cellular characteristics and potential mechanisms were evaluated using a
      protein microarray, and validated using western blot analysis. EPLIN expression
      was reduced in clinical prostate cancer sections, including hyperplasia (p <=
      0.001) and adenocarcinoma (p = 0.005), when compared to normal prostate tissue.
      EPLINalpha overexpression reduced cell growth, migration and invasion, and
      influenced transcript, protein and phosphoprotein expression of paxillin, FAK and
      Src. EPLIN knockdown increased the invasive and migratory nature of CA-HPV-10
      cells and also induced changes to FAK and Src total and/or phospho expression.
      Functional characterization of cellular migration and invasion in addition to FAK
      and Src inhibition demonstrated differential effects between control and
      EPLINalpha overexpression and EPLIN knockdown cell lines. This study highlights
      that EPLIN expression in prostate cancer is able to influence several aspects of
      cancer cell characteristics, including cell growth, migration and invasion. The
      mechanism of the tumor suppressive action of EPLIN remains to be fully
      elucidated; and this study proposes a role for EPLIN's ability to regulate the
      aggressive characteristics of prostate cancer cells partially through regulating
      FAK/Src signaling.

PMID- 30098001
TI  - The selective ROCK2 inhibitor KD025 reduces IL-17 secretion in human peripheral
      blood mononuclear cells independent of IL-1 and IL-6.
AB  - Reducing the activities of the pro-inflammatory cytokine IL-17 is an effective
      treatment strategy for several chronic autoimmune disorders. Rho-associated
      coiled-coil containing kinase 2 (ROCK2) is a member of the serine-threonine
      protein kinase family that regulates IL-17 secretion in T cells via signal
      transducer and activator of transcription 3 (STAT3)-dependent mechanism. We
      reported here that the selective ROCK2 inhibitor KD025 significantly reduced in
      vitro production of IL-17 in unfractionated human peripheral blood mononuclear
      cells (PBMCs) stimulated with the dectin-1 agonist Candida albicans. C. albicans
      induced IL-17 was reduced by 70% (p < 0.0001); a similar reduction (80%) was
      observed in PBMC stimulated with the Toll-like receptor 2 agonist Staphylococcus
      epidermidis (p < 0.0001). Treatment of PBMC with KD025 was not associated with a
      reduction in IL-1beta, IL-6 or IL-1alpha levels; in contrast, a 1.5 fold increase
      in the level of IL-1 receptor antagonist (IL-1Ra) was observed (p < 0.001). KD025
      down-regulated C. albicans-induced Myosin Light Chain and STAT3, whereas STAT5
      phosphorylation increased. Using anti-CD3/CD28 activation of the TCR, KD025
      similarly suppressed IL-17 independent of a reduction in IL-1beta. Thus, ROCK2
      directly regulates IL-17 secretion independent of endogenous IL-1 and IL-6
      supporting development of selective ROCK2 inhibitors for treatment of IL-17
      driven inflammatory diseases.

PMID- 30097997
TI  - Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau,
      alpha-synuclein, amyloid-beta and insulin resistance in neurodegenerative
      diseases.
AB  - While cytokines such as TNF have long been recognized as essential to normal
      cerebral physiology, the implications of their chronic excessive production
      within the brain are now also increasingly appreciated. Syndromes as diverse as
      malaria and lead poisoning, as well as non-infectious neurodegenerative diseases,
      illustrate this. These cytokines also orchestrate changes in tau, alpha
      synuclein, amyloid-beta levels and degree of insulin resistance in most
      neurodegenerative states. New data on the effects of salbutamol, an indirect anti
      TNF agent, on alpha-synuclein and Parkinson's disease, APOE4 and tau add
      considerably to the rationale of the anti-TNF approach to understanding, and
      treating, these diseases. Therapeutic advances being tested, and arguably useful
      for a number of the neurodegenerative diseases, include a reduction of excess
      cerebral TNF, whether directly, with a specific anti-TNF biological agent such as
      etanercept via Batson's plexus, or indirectly via surgically implanting stem
      cells. Inhaled salbutamol also warrants investigating further across the
      neurodegenerative disease spectrum. It is now timely to integrate this range of
      new information across the neurodegenerative disease spectrum, rather than keep
      seeing it through the lens of individual disease states.

PMID- 30098002
TI  - Deep learning applied to whole-brain connectome to determine seizure control
      after epilepsy surgery.
AB  - OBJECTIVE: We evaluated whether deep learning applied to whole-brain presurgical
      structural connectomes could be used to predict postoperative seizure outcome
      more accurately than inference from clinical variables in patients with mesial
      temporal lobe epilepsy (TLE). METHODS: Fifty patients with unilateral TLE were
      classified either as having persistent disabling seizures (SZ) or becoming
      seizure-free (SZF) at least 1 year after epilepsy surgery. Their presurgical
      structural connectomes were reconstructed from whole-brain diffusion tensor
      imaging. A deep network was trained based on connectome data to classify seizure
      outcome using 5-fold cross-validation. RESULTS: Classification accuracy of our
      trained neural network showed positive predictive value (PPV; seizure freedom) of
      88 +/- 7% and mean negative predictive value (NPV; seizure refractoriness) of 79
      +/- 8%. Conversely, a classification model based on clinical variables alone
      yielded <50% accuracy. The specific features that contributed to high accuracy
      classification of the neural network were located not only in the ipsilateral
      temporal and extratemporal regions, but also in the contralateral hemisphere.
      SIGNIFICANCE: Deep learning demonstrated to be a powerful statistical approach
      capable of isolating abnormal individualized patterns from complex datasets to
      provide a highly accurate prediction of seizure outcomes after surgery. Features
      involved in this predictive model were both ipsilateral and contralateral to the
      clinical foci and spanned across limbic and extralimbic networks.

PMID- 30098003
TI  - A 6-month prospective randomized controlled trial of remotely delivered group
      format epilepsy self-management versus waitlist control for high-risk people with
      epilepsy.
AB  - OBJECTIVE: Despite advances in care, many people with epilepsy have negative
      health events (NHEs) such as accidents, emergency department visits, and poor
      quality of life. "Self-management for people with epilepsy and a history of
      negative health events" (SMART) is a novel group format epilepsy self-management
      intervention. A community participatory approach informed the refinement of
      SMART, which was then tested in a 6-month randomized controlled trial of SMART (n
      = 60) versus waitlist control (WL, n = 60). METHODS: Participants were adults
      aged >=18 years with epilepsy and an NHE within the past 6 months (seizure,
      accident, self-harm attempt, emergency department visit, or hospitalization).
      Assessments were conducted at screening, baseline, 10 weeks, and 24 weeks (6
      months). Primary outcome was 6-month change in total NHE count. Additional
      outcomes included depression on the nine-item Patient Health Questionnaire and
      Montgomery-Asberg Depression Rating Scale, quality of life on the 10-item Quality
      of Life in Epilepsy, functioning on the 36-item Short-Form Health Survey, and
      seizure severity on the Liverpool Seizure Severity Scale. RESULTS: Mean age was
      41.3 years (SD = 11.82), 69.9% were African American, 74.2% were unemployed, and
      87.4% had an annual income < US$25 000; 57.5% had a seizure within 30 days of
      enrollment. Most NHEs were seizures. Six-month study attrition was 14.2% overall
      and similar between arms. Individuals randomized to SMART had greater reduction
      in total median NHEs from baseline to 6 months compared to WL (P = 0.04). SMART
      was also associated with improved nine-item Patient Health Questionnaire (P =
      0.032), Montgomery-Asberg Depression Rating Scale (P = 0.002), 10-item Quality of
      Life in Epilepsy (P < 0.001), and 36-item Short-Form Health Survey (P = 0.015
      physical health, P = 0.003 mental health) versus WL. There was no difference in
      seizure severity. SIGNIFICANCE: SMART is associated with reduced health
      complications and improved mood, quality of life, and health functioning in high
      risk people with epilepsy. Additional efforts are needed to investigate potential
      for scale-up.

PMID- 30098005
TI  - Low-temperature Raman spectroscopy reveals small chromophore distortion in
      primary photointermediate of proteorhodopsin.
AB  - Proteorhodopsin (PR) is a microbial rhodopsin functioning as a light-driven
      proton pump in aquatic bacteria. We performed low-temperature Raman measurements
      of PR to obtain the structure of the primary photoproduct, the K intermediate
      (PRK ). PRK showed the hydrogen-out-of-plane modes that are much less intense
      than those of bacteriorhodopsin as the prototypical light-driven proton pump from
      haloarchaea. The present results reveal the significantly relaxed chromophore
      structure in PRK , which can be coupled to the slow kinetics of the K
      intermediate. This structure suggests that PR transports protons using the small
      energy storage within the chromophore at the start of its photocycle.

PMID- 30098004
TI  - Inhibition of hyperpolarization-activated cyclic nucleotide-gated channels by
      beta-blocker carvedilol.
AB  - BACKGROUND AND PURPOSE: Carvedilol is a clinically effective beta-blocker broadly
      used for treating congestive heart failure (CHF), and several clinical trials
      have demonstrated that it shows a favourable effect compared with other beta
      blockers in patients with CHF. The mechanism underlying this beneficial effect of
      carvedilol compared to other beta-blockers is not clearly understood. In addition
      to beta-blockers, inhibitors of hyperpolarization-activated cyclic nucleotide
      (HCN)-gated channels, which play a critical role in spontaneous rhythmic activity
      in the heart, have also been proposed to be suitable drugs for reducing heart
      rate and, therefore, beneficial for treating CHF. In the present study, we
      investigated the effect of carvedilol on HCN channels. EXPERIMENTAL APPROACH:
      Whole-cell patch-clamp recordings were used to assess the effect of carvedilol on
      currents from wild-type and mutant HCN1, HCN2 and HCN4 channels expressed in CHO
      cells. KEY RESULTS: Carvedilol was the only beta-blocker tested that showed
      inhibitory effects on the major sinoatrial HCN channel isoform HCN4. Carvedilol
      inhibited HCN4 in a concentration-dependent manner with an EC50 of 4.4 MUM. In
      addition, carvedilol also inhibited HCN1 and HCN2 channels. Carvedilol blocked
      HCN channels by decelerating the rate of channel activation and increasing that
      of deactivation, and shifted the voltage-dependence of activation leftwards. Our
      data also showed that carvedilol, unlike other inhibitors of this channel
      (ivabradine and ZD7288), is not an 'open-channel' inhibitor of HCN4. CONCLUSIONS
      AND IMPLICATIONS: Carvedilol is a negative gating modulator of HCN channels. It
      represents a novel structure for future drug design of HCN channel inhibitors.

PMID- 30098006
TI  - Flawed mothering or infant signaling? The effects of deficient acoustic cues on
      ovine maternal response.
AB  - The neonate distress cry, which displays a similar acoustic structure across a
      range of mammalian species, is highly effective in attracting, even compelling,
      parental care. However, if this cry is defective, as found in human and rodent
      neonates with poor neurobehavioral function, is the signal less enticing? Using
      playback recordings of a ewe's own co-twins as stimuli in a two choice test, we
      compared the preference of each sheep dam for acoustic features of lamb distress
      calls to assess the impact of signal quality on maternal response. The results of
      this study indicate that lamb vocalizations with acoustic parameters reflecting
      poor vocal fold engagement and arousal were less likely to be preferred by their
      dam. Additionally, these calls were associated with delayed vocal initiation and
      poor infant survival behavior suggestive of subtle cognitive deficit; and support
      the possibility that, as in deer and rodents, ovine vocalizations within a
      specific fundamental frequency range may well be a trigger for optimal maternal
      behavior. This research has important implications for understanding failed
      maternal-young interactions in ungulate and other species, and for verifying
      standardization of infant stimuli used in maternal behavior studies.

PMID- 30098007
TI  - Use of topical antipsoriatic drugs in Denmark: a nationwide drug utilization
      study.
AB  - BACKGROUND: The reported real-life use of prescribed topical antipsoriatic drugs
      is conflicting and based on heterogeneous data sources. OBJECTIVES: To describe
      the utilization of topical antipsoriatic drugs among patients with psoriasis in
      Denmark. METHODS: A drug utilization study was performed based on nationwide
      Danish health registry data. We identified patients who received a first-time
      hospital diagnosis of psoriasis and redeemed at least one topical drug
      prescription in the period 2005-2015 (n = 7743). Patients were followed for 3
      years from the time of diagnosis. Use of topical and systemic antipsoriatic drugs
      was described, specified by the type of treatment. RESULTS: The total use of
      topical drugs was divided between corticosteroids with calcipotriol (31%),
      calcipotriol (6.5%), very potent corticosteroids (24%), potent corticosteroids
      (30%), moderate corticosteroids (7.2%) and corticosteroids with antimicrobials
      (1.6%). There was a 19% reduction in the overall use of topical drugs during the
      study period. Use increased around the time of diagnosis and the majority of
      patients redeemed more than two packages of topical drugs during the first year
      after being diagnosed. Regional differences in patients' use of topical drugs
      varied considerably. The distribution of use of topical drugs was uneven, with a
      minority of all patients (25%) using 70% of the total amount of topical
      treatment. There was a 70% increase in the use of methotrexate over the study
      period. Biologics were used by up to 6%. CONCLUSIONS: The study provides further
      evidence that the use of topical antipsoriatic drugs shows considerable
      heterogeneity over time and regional practices, and differences between patients.

PMID- 30098008
TI  - Everolimus in infants with tuberous sclerosis complex-related West syndrome:
      First results from a single-center prospective observational study.
AB  - Tuberous sclerosis complex (TSC) is the most common cause of West syndrome (WS).
      Currently available treatment options are ineffective in the majority of affected
      infants and/or associated with potential serious side effects. Based on the
      assumption that mTOR overactivation results in increased neuroexcitability in
      TSC, mTOR inhibitors have been studied as antiseizure therapy. As a result,
      everolimus recently received approval for the adjunctive treatment of patients
      aged >=2 years with refractory TSC-associated focal and secondary generalized
      seizures. However, efficacy and safety data for infants with TSC-associated WS
      are still lacking. Therefore, a prospective open-label observational study was
      initiated at our center, to evaluate everolimus add-on treatment in infants with
      TSC-associated WS, previously refractory to standard treatment. For this
      preliminary report, data from four male infants with TSC2 and a median
      observation period of 13 (range = 8-42) months after treatment initiation were
      analyzed. Two infants showed electroclinical remission until day 14 after
      everolimus treatment initiation. In one additional infant, hypsarrhythmia
      resolved. No relapse after initial response was documented. Developmental
      progress improved in three infants. Tolerability was similar to that described in
      older children. According to our preliminary results, everolimus appears to have
      the potential to treat successfully both spasms and hypsarrhythmia in infants
      with TSC-associated WS, contributing to better developmental progress.

PMID- 30098009
TI  - Consequences of Cre-mediated deletion of Ciz1 exon 5 in mice.
AB  - CIZ1 plays a role in DNA synthesis at the G1/S checkpoint. Ciz1 gene-trap null
      mice manifest motor dysfunction, cell-cycle abnormalities, and DNA damage. In
      contrast, it has previously been reported that mouse embryonic fibroblasts
      derived from presumed Ciz1 knock-out mice (Ciz1tm1.1Homy/tm1.1Homy ) generated by
      crossing Cre-expressing mice with exon 5-floxed mice (Ciz1tm1Homy/tm1Homy ) do
      not exhibit evidence of enhanced DNA damage following gamma-irradiation or cell
      cycle defects. Here, we report that Ciz1tm1.1Homy/tm1.1Homy mice show loss of
      Ciz1 exon 5 but are neurologically normal and express abnormal transcripts
      (Ciz1DeltaE5/DeltaE5 mice) that are translated into one or more proteins of
      approximate wild-type size. Therefore, Ciz1tm1.1Homy/tm1.1Homy mice
      (Ciz1DeltaE5/DeltaE5 ) lose residues encoded by exon 5 but may gain function from
      novel amino acid sequences.

PMID- 30098010
TI  - Return of individual results in epilepsy genomic research: A view from the field.
AB  - Genomic findings are emerging rapidly in 2 large, closely related epilepsy
      research consortia: the Epilepsy Phenome/Genome Project and Epi4K. Disclosure of
      individual results to participants in genomic research is increasingly viewed as
      an ethical obligation, but strategies for return of results were not included in
      the design of these consortia, raising complexities in establishing criteria for
      which results to offer, determining participant preferences, managing the large
      number of sites involved, and covering associated costs. Here, we describe the
      challenges faced, alternative approaches considered, and progress to date.
      Experience from these 2 consortia illustrates the importance, for genomic
      research in epilepsy and other disorders, of including a specific plan for return
      of results in the study design, with financial support for obtaining clinical
      confirmation and providing ongoing support for participants. Participant
      preferences for return of results should be established at the time of
      enrollment, and methods for allowing future contacts with participants should be
      included. In addition, methods should be developed for summarizing meaningful,
      comprehensible information about findings in the aggregate that participants can
      access in an ongoing way.

PMID- 30098012
TI  - Surviving childhood cancer: a systematic review of studies on risk and
      determinants of adverse socioeconomic outcomes.
AB  - Substantial improvements in childhood cancer survival have resulted in a steadily
      increasing population of childhood cancer survivors. Whereas somatic late effects
      have been assessed in many studies, less is known about the impact of childhood
      cancer on socioeconomic outcomes in survivors. The aim of this article was to
      evaluate and summarise the evidence on the socioeconomic conditions of childhood
      cancer survivors and to identify survivors at particular risk of adverse
      socioeconomic outcomes. An extensive literature search of three electronic
      databases was conducted. Of 419 articles identified, 52 met the inclusion
      criteria. All the selected articles were appraised for quality, and findings were
      summarised in a narrative synthesis. Childhood cancer survivors were at higher
      risk of adverse socioeconomic outcomes with regard to educational achievement,
      income and social security benefits than the general population or a sibling
      comparison group. The risks for unemployment and a lower occupational position
      were significantly increased only for survivors of a central nervous system
      tumour. Notably, survivors of central nervous system tumours, survivors treated
      with cranial radiotherapy and those diagnosed at younger age independent of
      cancer type were determinants of particular adverse socioeconomic outcomes. Given
      the increasing population of childhood cancer survivors, targeted follow-up
      interventions and support strategies addressing not only the somatic and
      psychiatric late effects but also the socioeconomic difficulties that some
      childhood cancer survivors face is of high importance to reduce social inequity,
      and ensure a high quality of life after childhood cancer.

PMID- 30098013
TI  - Reliable identification of women with CIN3+ using hrHPV genotyping and
      methylation markers in a cytology-screened referral population.
AB  - Cervical screening aims to identify women with high-grade squamous
      intraepithelial lesion/cervical intraepithelial neoplasia 2-3 (HSIL/CIN2-3) or
      invasive cervical cancer (ICC). Identification of women with severe premalignant
      lesions or ICC (CIN3+) could ensure their rapid treatment and prevent
      overtreatment. We investigated high-risk human papillomavirus (hrHPV) detection
      with genotyping and methylation of FAM19A4/miR124-2 for detection of CIN3+ in 538
      women attending colposcopy for abnormal cytology. All women had an additional
      cytology with hrHPV testing (GP5+/6+-PCR-EIA+), genotyping (HPV16/18,
      HPV16/18/31/45), and methylation analysis (FAM19A4/miR124-2) and at least one
      biopsy. CIN3+ detection was studied overall and in women <30 (n = 171) and >=30
      years (n = 367). Positivity for both rather than just one methylation markers
      increased in CIN3, and all ICC was positive for both. Overall sensitivity and
      specificity for CIN3+ were, respectively, 90.3% (95%CI 81.3-95.2) and 31.8%
      (95%CI 27.7-36.1) for hrHPV, 77.8% (95%CI 66.9-85.8) and 69.3% (95%CI 65.0-73.3)
      for methylation biomarkers and 93.1% (95%CI 84.8-97.0) and 49.4% (95%CI 44.8
      53.9) for combined HPV16/18 and/or methylation positivity. For CIN3, hrHPV was
      found in 90.9% (95%CI 81.6-95.8), methylation positivity in 75.8% (95%CI 64.2
      84.5) and HPV16/18 and/or methylation positivity in 92.4% (95%CI 83.5-96.7). In
      women aged >=30, the sensitivity of combined HPV16/18 and methylation was
      increased (98.2%, 95%CI 90.6-99.7) with a specificity of 46.3% (95%CI 40.8-51.9).
      Combination of HPV16/18 and methylation analysis was very sensitive and offered
      improved specificity for CIN3+, opening the possibility of rapid treatment for
      these women and follow-up for women with potentially regressive, less advanced,
      HSIL/CIN2 lesions.

PMID- 30098011
TI  - P2X7 as a scavenger receptor for innate phagocytosis in the brain.
AB  - The P2X7 receptor has been widely studied for its ATP-induced pro-inflammatory
      effect, but in the absence of a ligand, P2X7 has a second function as a scavenger
      receptor, which is active in the development of the human brain. The scavenger
      activity of P2X7 is only evident in the absence of serum but is fully active in
      cerebrospinal fluid. P2X7 on the cell surface is present as a membrane complex,
      and an attachment to non-muscle myosin of the cytoskeleton is required for
      particle engulfment. Selective antagonists of P2X7 pro-inflammatory function have
      little effect on phagocytosis, but inheritance of a variant haplotype spanning
      the P2RX7 and P2RX4 genes has been associated with loss of P2X7-mediated
      phagocytosis. Recent studies in mice suggest that the innate phagocytosis
      mediated by P2X7 receptors declines with ageing. Thus, defective P2X7-mediated
      phagocytosis may contribute to age-related neuro-degenerative diseases including
      Alzheimer's disease, age-related macular degeneration and primary progressive
      multiple sclerosis.

PMID- 30098014
TI  - Patterns of use and optimal timing of antenatal corticosteroids in twin compared
      with singleton pregnancies.
AB  - INTRODUCTION: Previous reports have shown that suboptimal antenatal
      corticosteroids administration occurs in most cases. However, as multifetal
      gestations were either excluded or constituted a small proportion of the
      participants in these studies, little is known about the patterns of use of
      antenatal corticosteroids in twin pregnancies. MATERIAL AND METHODS: We reviewed
      the records of women who received antenatal corticosteroids and delivered between
      240/7 and 346/7 weeks of gestation during 2015-2017 at 2 university hospitals.
      Optimal antenatal corticosteroids timing was defined as delivery >=24 hours <=7
      days from the previous antenatal corticosteroids course. RESULTS: Of 424
      pregnancies, 307 (72.4%) were singleton and 117 were (27.6%) twin. For twin
      compared with singleton pregnancies, gestational age at initial antenatal
      corticosteroids administration was lower (P = 0.02), the proportion of deliveries
      within the optimal window of the initial antenatal corticosteroids course was
      lower (19.7% vs 33.2%, P = 0.001), and the proportion of women eligible for a
      rescue antenatal corticosteroids course was higher (58.1% vs 32.9%, P < 0.0001).
      However, despite similar rates of rescue antenatal corticosteroids administration
      (P = 0.64), the overall rate of delivery within any optimal window (either
      initial or rescue course) was lower in twin than singleton pregnancies (26.5% vs
      42.3%, P = 0.004), and the antenatal corticosteroids-to-delivery interval was
      longer (median 6.9 vs 4.2 days, P = 0.0009). In multivariate analysis, optimal
      antenatal corticosteroids administration was negatively associated with twin
      pregnancy (P = 0.04) and preterm labor (P = 0.05), and positively associated with
      the presence of gestational hypertensive disorders (P = 0.03). CONCLUSIONS: Twin
      pregnancy is an independent risk factor for suboptimal antenatal corticosteroids
      administration. Directed efforts should be made to improve the utilization of
      antenatal corticosteroids in this vulnerable group of women.

PMID- 30098015
TI  - A Multicomponent Model to Improve Hospital Care of Older Adults with Cognitive
      Impairment: A Propensity Score-Matched Analysis.
AB  - OBJECTIVES: To determine whether a multicomponent intervention improves care in
      hospitalized older adults with cognitive impairment. DESIGN: One-year
      retrospective chart review with propensity score matching on critical demographic
      and clinical variables was used to compare individauls with cognitive impairmenet
      on intervention and nonintervention units. SETTING: Large tertiary medical
      center. PARTICIPANTS: All hospitalized individuals age 65 and older with
      cognitive impairment admitted to medicine who required constant or enhanced
      observation for behavioral and psychological symptoms. INTERVENTION:
      Multicomponent intervention (geographic unit cohorting, multidisciplinary
      approach, patient engagement specialists (PES), staff education) or usual care.
      MEASUREMENTS: In-hospital mortality, length of stay, readmission, management of
      behavioral disturbances. RESULTS: After propensity score matching, 476 of the 712
      intervention visits were pair-matched with 476 of the 558 usual care visits.
      Matching was successful in balancing baseline covariates between intervention and
      usual care units. Individuals admitted to the intervention unit had lower in
      hospital mortality (1.1% vs 2.9%, p=0.05) and shorter stays (5.0 vs 5.8 days,
      p=0.04). There was no difference in discharge home (p=0.90) or 30-day readmission
      rates (p=0.44). Individuals on the intervention unit were less likely than those
      receivng usual care to have an order for constant (12.0% vs 45.8%, p<0.01) or
      enhanced (22.1% vs 79.6%, p<0.01) observation, to be taking benzodiazepines
      (26.3% vs 38.0%, p<0.01), to be taking nothing by mouth (29.6% vs 40.8%, p=0.01),
      to be on bedrest (17.0% vs 25.8%, p=0.01), to be taking antipsychotics (41.2% vs
      54.0%, p<0.01), or to have restraints (3.2% vs 6.9%, p=.01). CONCLUSION: A
      multicomponent intervention of geographic cohorting, multidisciplinary approach,
      PES, and staff education may offer a new paradigm in the management of
      hospitalized older adults with cognitive impairment.

PMID- 30098016
TI  - Infectious events and associated risk factors in mycosis fungoides/Sezary
      syndrome: a retrospective cohort study.
AB  - BACKGROUND: Infections are one of the major causes of death in patients with
      advanced-stage mycosis fungoides (MF) or Sezary syndrome (SS). However, few
      recent data are available on the characteristics and risk factors of these
      infectious events. OBJECTIVES: To describe infectious events occurring in a
      cohort of patients with MF/SS, and to identify associated clinical and biological
      risk factors. METHODS: A retrospective cohort study was performed to investigate
      infectious events and associated factors in patients diagnosed with MF (stage IB
      and beyond) or SS followed from May 2011 to May 2016 at the University Hospital
      of Bordeaux, France. RESULTS: Seventy-one patients with complete follow-up were
      included. Eighty infectious events were recorded in 40 patients, including 28
      skin and soft tissue infections and 25 cases of pneumonia. Opportunistic
      infections, which are usually associated with depleted cell-mediated immunity,
      were scarce (9%). In multivariate analysis, cardiac, renal or lung comorbidities
      [odds ratio (OR) 7.2, 95% confidence interval (CI) 3.3-15.9; P = 0.002], SS (OR
      8.8, 95% CI 7.7-10.2; P = 0.037) and lymphocyte count < 0.5 * 109 cells L-1 (OR
      6.4, 95% CI 1.5-27.4; P = 0.004) were significantly associated with a higher risk
      of infection. CONCLUSIONS: Opportunistic germs were rarely recorded, but their
      incidence was probably prevented by adequate prophylaxis (ongoing in 28% of
      patients). As in patients living with AIDS, pneumonias were frequent. On the
      other hand, bacterial cutaneous infections represent a specific pattern in
      patients with MF/SS. Patients with chronic organ failure, lymphocytopenia and SS
      should be considered as being at high risk for infectious events. Pneumococcal
      vaccination should be systematically recommended, and prophylaxis with co
      trimoxazole and valaciclovir when the CD4 count is < 0.2 * 109 cells L-1 .

PMID- 30098017
TI  - Vision Impairment and Risk of Dementia: Findings from the English Longitudinal
      Study of Ageing.
AB  - OBJECTIVES: To determine whether vision impairment is independently associated
      cross-sectionally and longitudinally with dementia. DESIGN: Retrospective cohort
      study. SETTING: English Longitudinal Study of Ageing. PARTICIPANTS: Individuals
      aged 50 and older MEASUREMENTS: Cross-sectional association between self-rated
      vision (poor or blind, moderate, normal) and dementia was analyzed, adjusting for
      potential confounders (sex, wealth, education, cardiovascular risk factors) using
      multivariable logistic regression. We also modelled the adjusted longitudinal
      association between vision impairment and dementia over an average of 11 years of
      follow-up using Cox proportional hazards regression for individuals aged 50 to 69
      and those aged 70 and older. RESULTS: After adjustment for confounders,
      participants who rated their vision as moderate were 2.0 (95% confidence interval
      (CI)=1.4-3.1) times as likely as those with normal vision to have dementia, and
      those who rated their vision as poor were 4.0 (95% CI=2.6-6.1) times as likely.
      Longitudinally, individuals aged 50 to 69 who rated their vision as moderate
      (1.8, 95% CI=1.0-3.0) or poor (3.6, 95% CI=1.1-11.8) were at greater risk of
      developing dementia than those who rated their vision as normal. There was no
      significant difference in risk in those aged 70 and older. CONCLUSION: Our study
      confirms and extends findings from other countries, demonstrating cross-sectional
      associations between moderate and poor self-rated vision and dementia in England
      in all participants aged 50 and older and longitudinally over an 11-year period
      in those aged 50 to 69. These results help establish vision loss as a risk factor
      for dementia, although it is unclear why. Research is needed to determine whether
      screening and treatment for vision loss may slow cognitive decline.

PMID- 30098018
TI  - A trajectory analysis of childhood motor development following stress in
      pregnancy: The QF2011 flood study.
AB  - This prospective, longitudinal cohort study examined the effects of flood-related
      stress in pregnancy on the trajectory of children's motor development; and the
      moderating effects of gestational timing of the flood or sex of the child. Women
      who were pregnant during a severe flood reported on their objective flood-related
      experiences, emotional reactions, and cognitive appraisal of the disaster. At 2-,
      6-, 16-months, 21/2- and 4-years postpartum, mothers' assessed their children's
      fine and gross motor development using the Ages and Stages-3 Questionnaire. High
      objective flood-exposure, or a negative appraisal, especially in later pregnancy,
      predicted poorer gross motor skills which rapidly improved across early
      childhood. Children's fine motor skill was influenced by the sex of the child
      with improvements in girls' fine motor skills over time, but not boys'. This
      demonstrates that stress in pregnancy has enduring influences on gross, but not
      fine, motor skills. Results are discussed in relation to fetal programming and
      stress appraisal theory.

PMID- 30098020
TI  - Under pressure: biomechanical limitations of developing pneumatocysts in the bull
      kelp (Nereocystis luetkeana, Phaeophyceae).
AB  - Maintaining buoyancy with gas-filled floats (pneumatocysts) is essential for some
      subtidal kelps to achieve an upright stature and compete for light . However, as
      these kelps grow up through the water column, pneumatocysts are exposed to
      substantial changes in hydrostatic pressure, which could cause complications as
      internal gases may expand or contract, potentially causing them to rupture,
      flood, and lose buoyancy. In this study, we investigate how pneumatocysts of
      Nereocystis luetkeana resist biomechanical stress and maintain buoyancy as they
      develop across a hydrostatic gradient. We measured internal pressure, material
      properties, and pneumatocyst geometry across a range of thallus sizes and
      collection depths to identify strategies used to resist pressure-induced
      mechanical failure. Contrary to expectations, all pneumatocysts had internal
      pressures less than atmospheric pressure, ensuring that thalli are always exposed
      to a positive pressure gradient and compressional loads, indicating that they are
      more likely to buckle than rupture at all depths. Small pneumatocysts collected
      from depths between 1 and 9 m (inner radius = 0.4-1.0 cm) were demonstrated to
      have elevated wall stresses under high compressive loads and are at greatest risk
      of buckling. Although small kelps do not adjust pneumatocyst material properties
      or geometry to reduce wall stress as they grow, they are ~3.4 times stronger than
      they need to be to resist hydrostatic buckling. When tested, pneumatocysts
      buckled around 35 m depth, which agrees with previous measures of lower limits
      due to light attenuation, suggesting that hydrostatic pressure may also define
      the lower limit of Nereocystis in the field.

PMID- 30098019
TI  - Efficacy of treprostinil in the SU5416-hypoxia model of severe pulmonary arterial
      hypertension: haemodynamic benefits are not associated with improvements in
      arterial remodelling.
AB  - BACKGROUND AND PURPOSE: Pulmonary arterial hypertension (PAH) is a life
      threatening disease that leads to progressive pulmonary hypertension, right heart
      failure and death. Parenteral prostaglandins (PGs), including treprostinil, a
      prostacyclin analogue, represent the most effective medical treatment for severe
      PAH. We investigated the effect of treprostinil on established severe PAH and
      underlying mechanisms using the rat SU5416 (SU, a VEGF receptor-2 inhibitor)
      chronic hypoxia (Hx) model of PAH. EXPERIMENTAL APPROACH: Male Sprague Dawley
      rats were injected with SU (20 mg.kg-1 , s.c.) followed by 3 weeks of Hx (10% O2
      ) to induce severe PAH. Four weeks post-SU injection, baseline right ventricular
      (RV) systolic pressure (RVSP) was measured, and the rats were randomized to
      receive vehicle or treprostinil treatment (Trep-100: 100 ng.kg-1 .min-1 or Trep
      810: 810 ng.kg-1 .min-1 ). Following 3 weeks of treatment, haemodynamic and
      echocardiographic assessments were performed, and tissue samples were collected
      for protein expression and histological analysis. KEY RESULTS: At week 7, no
      difference in RVSP or RV hypertrophy was observed between vehicle and Trep-100;
      however, Trep-810 significantly reduced RVSP and RV hypertrophy. Trep-810
      treatment significantly improved cardiac structure and function. Further, a short
      term infusion of treprostinil in rats with established PAH at 4 weeks post-SU
      produced an acute, dose-dependent reduction in RVSP consistent with a vasodilator
      effect. However, chronic Trep-810 treatment did not alter media wall thickness,
      degree of vascular occlusion or total vessel count in the lungs. CONCLUSIONS AND
      IMPLICATIONS: Treprostinil exerts therapeutic benefits in PAH through decreased
      vascular resistance and improved cardiac structure and function; however,
      treprostinil treatment does not have direct impact vascular remodelling.

PMID- 30098022
TI  - In Response to Upper Airway Stimulation Therapy and Prior Airway Surgery for
      Obstructive Sleep Apnea.

PMID- 30098021
TI  - Enteral nutrition for maintenance of remission in Crohn's disease.
AB  - BACKGROUND: Prevention of relapse is a major issue in the management of quiescent
      Crohn's disease (CD). Current therapies (e.g. methotrexate, biologics, 6
      mercaptopurine and azathioprine) may be effective for maintaining remission in
      CD, but these drugs may cause significant adverse events. Interventions that are
      effective and safe for maintenance of remission in CD are desirable. OBJECTIVES:
      The primary objectives were to evaluate the efficacy and safety of enteral
      nutrition for the maintenance of remission in CD and to assess the impact of
      formula composition on effectiveness. SEARCH METHODS: We searched MEDLINE,
      Embase, CENTRAL, the Cochrane IBD Group Specialized Register and
      clinicaltrials.gov from inception to 27 July 2018. We also searched references of
      retrieved studies and reviews. SELECTION CRITERIA: Randomised controlled trials
      (RCTs) including participants of any age with quiescent CD were considered for
      inclusion. Studies that compared enteral nutrition with no intervention, placebo
      or any other intervention were selected for review. DATA COLLECTION AND ANALYSIS:
      Two authors independently screened studies for inclusion, extracted data and
      assessed methodological quality using the Cochrane risk of bias tool. The primary
      outcome was clinical or endoscopic relapse as defined by the primary studies.
      Secondary outcomes included anthropometric measures (i.e. height and weight),
      quality of life (QoL), adverse events, serious adverse events and withdrawal due
      to adverse events. We calculated the risk ratio and 95% confidence interval (CI)
      for dichotomous outcomes. For continuous outcomes, we calculated the mean
      difference and 95% CI. A random-effects model was used for the statistical
      analysis. We used the GRADE criteria to assess the overall certainty of the
      evidence supporting the primary outcome and selected secondary outcomes. MAIN
      RESULTS: Four RCTs (262 adult participants) met the inclusion criteria. One study
      (N = 33) compared an elemental diet to a non-elemental (polymeric) diet. One
      study (N = 51) compared a half elemental diet to a regular free diet. Another
      study (N = 95) compared an elemental diet to 6-mercaptopurine (6-MP) or a no
      treatment control group. One study (N= 83) compared a polymeric diet to
      mesalamine. Two studies were rated as high risk of bias due to lack of blinding
      or incomplete outcome data. The other two studies were judged to have an unclear
      risk of bias. The studies were not pooled due to differences in control
      interventions and the way outcomes were assessed.The effect of an elemental diet
      compared to a polymeric diet on remission rates or withdrawal due to adverse
      events is uncertain. Fifty-eight per cent (11/19) of participants in the
      elemental diet group relapsed at 12 months compared to 57% (8/14) of participants
      in the polymeric diet group (RR 1.01, 95% CI 0.56 to 1.84; very low certainty
      evidence). Thirty-two per cent (6/19) of participants in the elemental diet group
      were intolerant to the enteral nutritional formula because of taste or smell and
      were withdrawn from the study in the first 2 weeks compared to zero participants
      (0/14) in the polymeric diet group (RR 9.75, 95% CI 0.59 to 159.93; low certainty
      evidence). Anthropometric measures, QoL, adverse events and serious adverse
      events were not reported as outcomes.The effect of an elemental diet (half of
      total daily calorie requirements) compared to a normal free diet on relapse rates
      is uncertain. Thirty-five per cent (9/26) of participants in the elemental diet
      group relapsed at 12 months compared to 64% (16/25) of participants in the free
      diet group (RR 0.54, 95% CI 0.30 to 0.99; very low certainty evidence). No
      adverse events were reported. This study reported no differences in weight change
      between the two diet groups. Height and QoL were not reported as outcomes.The
      effect of an elemental diet compared to 6-MP on relapse rates or adverse events
      is uncertain. Thirty-eight per cent (12/32) of participants in the elemental diet
      group relapsed at 12 months compared to 23% (7/30) of participants in the 6-MP
      group (RR 1.61; 95% CI 0.73 to 3.53; very low certainty evidence). Three per cent
      (1/32) of participants in the elemental diet group had an adverse event compared
      to 13% (4/30) of participants in the 6-MP group (RR 0.23, 95% CI 0.03 to 1.98;
      low certainty evidence). Adverse events in the elemental diet group included
      surgery due to worsening CD. Adverse events in the 6-MP group included liver
      injury (n = 2), hair loss (n = 1) and surgery due to an abscess (n = 1). No
      serious adverse events or withdrawals due to adverse events were reported.
      Weight, height and QoL were not reported as outcomesThe effect of a polymeric
      diet compared to mesalamine on relapse rates and weight is uncertain. Forty-two
      per cent (18/43) of participants in the polymeric diet group relapsed at 6 months
      compared to 55% (22/40) of participants in the mesalamine group (RR 0.76; 95% CI
      0.49 to 1.19; low certainty evidence). The mean difference in weight gain over
      the study period was 1.9 kg higher in the polymeric diet group compared to
      mesalamine (95% CI -4.62 to 8.42; low certainty evidence). Two participants in
      the polymeric diet group experienced nausea and four had diarrhoea. It is unclear
      if any participants in the mesalamine group had an adverse event. Height, QoL,
      serious adverse events and withdrawal due to adverse events were not reported as
      outcomes. AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this
      review are uncertain and no firm conclusions regarding the efficacy and safety of
      enteral nutrition in quiescent CD can be drawn. More research is needed to
      determine the efficacy and safety of using enteral nutrition as maintenance
      therapy in CD. Currently, there are four ongoing studies (estimated enrolment of
      280 participants). This review will be updated when the results of these studies
      are available.

PMID- 30098023
TI  - Inhibition of adventitious root development in apple rootstocks by cytokinin is
      based on its suppression of adventitious root primordia formation.
AB  - Cytokinin (CK) inhibits adventitious root (AR) formation in stem cuttings. Little
      is known, however, about the mechanism underlying the inhibitory effect. In this
      study, 2 mg l-1 of exogenous 6-benzyl adenine (6-BA) was administered to 3 and 7
      day-old apple rootstocks 'M.26' cuttings (3 and 7 days 6-BA) by transferring them
      from a rooting medium containing indole-3-butanoic acid to the medium containing
      6-BA. Anatomical and morphological observations revealed that the exogenous
      application of 6-BA inhibited primordia formation in the 3 days 6-BA but not the
      7 days 6-BA group. The concentration of auxin (IAA), the ratios of IAA/CK and
      IAA/abscisic acid were lower in 3 days 6-BA than in 7 days 6-BA. Expression
      analysis of genes known to be associated with AR formation was also analyzed. In
      the 3 days 6-BA group, high level of CK inhibited the synthesis and transport of
      auxin, as a result, low endogenous auxin level suppressed the auxin signaling
      pathway genes, as were other AR development and cell cycle related genes; all of
      which had an inhibitory impact on AR primordium formation. On the contrary, low
      CK level in the 7 days 6-BA, reduced the inhibitory impact on auxin levels,
      leading to an upregulated expression of genes known to promote AR primordia
      formation. Collectively, our data indicated that 3-7 days is the time period in
      which AR primordia formation occurs in cuttings of 'M.26' and that the inhibition
      of AR development by CK is due to the suppression of AR primordia development
      over 3-7 days period after culturing in rooting medium.

PMID- 30098024
TI  - Intranasal Lidocaine for Acute Management of Primary Headaches: A Systematic
      Review.
AB  - Intranasal lidocaine has been studied and recommended as an alternative in the
      management of acute headache. The objective of this systematic review was to
      evaluate the efficacy and safety of intranasal lidocaine in the acute management
      of primary headaches. The MEDLINE (1946 to May 2018), EMBASE (1974 to May 2018),
      Cochrane Central Register of Controlled Trials (2008 to May 2018), Cumulative
      Index to Nursing and Allied Health Literature (CINAHL) (1982 to May 2018), and
      ClincialTrials.gov online databases were searched. Studies conducted in patients
      with acute primary headache were included if lidocaine was compared with placebo
      or alternative treatments, lidocaine dosing was specified, and patients' pain
      before and after treatment were clearly reported. Six studies met the inclusion
      criteria. Intranasal lidocaine demonstrated potential benefit over placebo in
      acute pain reduction and need for rescue medication only in the four studies
      deemed to be of poor quality, not in the two fair-quality studies. No study
      reported benefit in preventing headache recurrence or repeat visits to the
      emergency department. Lidocaine was associated with significantly higher rates of
      adverse events compared with placebo and may result in lower rates of patient
      satisfaction. There is insufficient evidence to support the use of intranasal
      lidocaine in acute management of primary headaches. Further research is warranted
      to better elucidate whether intranasal lidocaine has a role in the management of
      specific primary headache subtypes and whether there is an optimal regimen.

PMID- 30098026
TI  - Histone H3K36M mutation and trimethylation patterns in chondroblastoma.
AB  - AIMS: Histones are essential components of chromatin, and mutations in histones
      lead to alterations in methylation and acetylation, which play an important role
      in tumorigenesis. Most of the chondroblastomas harbour the H3K36M mutation. With
      the availability of a mutation-specific antibody, we sought to assess the
      sensitivity of this antibody and the alterations of histone methylation in a
      series of chondroblastoma cases. METHODS AND RESULTS: Immunohistochemical
      staining with antibodies against H3K36M, trimethylated histones (H3K27me3 and
      H3K36me3) and an osteoblastic marker (SATB2) was performed on 27 chondroblastomas
      from 27 patients. The clinical and radiological characteristics of each patient
      were reviewed. All 27 tumours showed typical radiological and histological
      features of chondroblastoma, with a subset of cases showing secondary aneurysmal
      bone cyst changes (11/27), giant-cell-rich foci (4/27), and matrix-rich areas
      mimicking chondromyxoid fibroma (1/27). All except one case (26/27, 96%) showed
      positive H3K36M immunostaining (nuclear). In the majority of cases, there was a
      diffuse staining pattern. Immunohistochemical staining for H3K27me3 and H3K36me3
      showed a heterogeneous staining pattern in all cases, regardless of mutation
      status. None of the cases showed loss of positivity or diffuse positivity. Focal
      or diffuse SATB2 expression was seen in 21 of 26 tumours (81%). CONCLUSION: Our
      results demonstrate that the vast majority of chondroblastomas are positive for
      H3K36M by immunohistochemical analysis, confirming its diagnostic value. H3K27me3
      expression and H3K36me3 expression are heterogeneous in these tumours.

PMID- 30098025
TI  - Development of deep neural network for individualized hepatobiliary toxicity
      prediction after liver SBRT.
AB  - BACKGROUND: Accurate prediction of radiation toxicity of healthy organs-at-risks
      (OARs) critically determines the radiation therapy (RT) success. The existing
      dose-volume histogram-based metric may grossly under/overestimate the therapeutic
      toxicity after 27% in liver RT and 50% in head-and-neck RT. We propose the novel
      paradigm for toxicity prediction by leveraging the enormous potential of deep
      learning and go beyond the existing dose/volume histograms. EXPERIMENTAL DESIGN:
      We employed a database of 125 liver stereotactic body RT (SBRT) cases with follow
      up data to train deep learning-based toxicity predictor. Convolutional neural
      networks (CNNs) were applied to discover the consistent patterns in 3D dose plans
      associated with toxicities. To enhance the predicting power, we first pretrain
      the CNNs with transfer learning from 3D CT images of 2644 human organs. CNNs were
      then trained on liver SBRT cases. Furthermore, nondosimetric pretreatment
      features, such as patients' demographics, underlying liver diseases, liver
      directed therapies, were inputted into the fully connected neural network for
      more comprehensive prediction. The saliency maps of CNNs were used to estimate
      the toxicity risks associated with irradiation of anatomical regions of specific
      OARs. In addition, we applied machine learning solutions to map numerical
      pretreatment features with hepatobiliary toxicity manifestation. RESULTS: Among
      125 liver SBRT patients, 58 were treated for liver metastases, 36 for
      hepatocellular carcinoma, 27 for cholangiocarcinoma, and 4 for other histologies.
      We observed that CNN we able to achieve accurate hepatobiliary toxicity
      prediction with the AUC of 0.79, whereas combining CNN for 3D dose plan analysis
      and fully connected neural networks for numerical feature analysis resulted in
      AUC of 0.85. Deep learning produces almost two times fewer false-positive
      toxicity predictions in comparison to DVH-based predictions, when the number of
      false negatives, i.e., missed toxicities, was minimized. The CNN saliency maps
      automatically estimated the toxicity risks for portal vein (PV) regions. We
      discovered that irradiation of the proximal portal vein is associated with two
      times higher toxicity risks (risk score: 0.66) that irradiation of the left
      portal vein (risk score: 0.31). CONCLUSIONS: The framework offers clinically
      accurate tools for hepatobiliary toxicity prediction and automatic identification
      of anatomical regions that are critical to spare during SBRT.

PMID- 30098027
TI  - Predicting lesion size by accumulated thermal dose in MR-guided focused
      ultrasound for essential tremor.
AB  - PURPOSE: To correlate the accumulated thermal dose (ATD) with lesion size in
      magnetic resonance (MR)-guided focused ultrasound (MRgFUS) thalamotomy to help
      guide future clinical treatments. MATERIALS AND METHODS: Thirty-six patients with
      medication-refractory essential tremor were treated using a commercial MRgFUS
      brain system (ExAblate 4000, InSightec) in a 3T MR scanner (MR750, GE
      Healthcare). Intraoperative MR-thermometry was performed to measure the induced
      temperature and thermal dose distributions (thermal coefficient = -0.00909 ppm/
      degrees C). The ATD was calculated over multiple sonications with appropriate
      corrections for spatial-shifting artifacts. The ATD profile sizes obtained for
      dose values of 17, 40, 100, 200, and 240 cumulative equivalent minutes at 43
      degrees C (CEM) were correlated with the corresponding lesion sizes measured via
      axial T1- and T2-weighted MR images acquired 1 day post-treatment. RESULTS: Of a
      total of 232 included sonications, 83 required corrections for off-resonance
      induced spatial-shifting artifacts (correction range = [1.1,2.2] mm). The mean
      lesion sizes measured on T2-weighted MR images (6.2 +/- 1.3 mm, mean +/- SD) were
      15% larger than those measured on corresponding T1-weighted MR images (5.3 +/-
      1.2 mm, mean +/- SD). The ATD values that provided the best correlations with the
      measured lesion sizes on T2- and T1-weighted MR images were 100 and 200 CEM,
      respectively. CONCLUSION: The ATD was correlated with lesion size measured 1 day
      following MRgFUS thalamotomy for essential tremor. These data provide useful
      information for predicting brain lesion size and determining treatment endpoints
      in future clinical MRgFUS procedures.

PMID- 30098029
TI  - Benchmarking the DACS-integrated Radiation Dose Monitor(r) skin dose mapping
      software using XR-RV3 Gafchromic(r) films.
AB  - PURPOSE: To perform a benchmark of a new DACS-integrated patient skin dose
      mapping solution using on-phantom measurements with Gafchromic(r) films.
      MATERIALS AND METHODS: To calculate cumulative patient skin dose distribution
      with 1-cm2 resolution, a Radiation Dose Monitor (RDM, Medsquare), using the
      Radiation Dose Structured Report (RDSR), tabulated backscatter and mass energy
      absorption coefficients together with site-specific corrections for table,
      mattress attenuation, and air kerma calibration factor. Peak skin dose (PSD) and
      two-dimensional (2D) skin dose distributions calculated with RDM were compared
      against on-phantom measurements with XR-RV3 Gafchromic(r) films considering two
      widely used x-ray equipment. Seventeen different settings which include simple
      and multiple beam projections with extreme angulations (up to 75 degrees ), all
      available fields-of-view (FOVs 48-11 cm), additional collimation, variable table
      height and lateral positions, and variable phantom thickness (12, 20, and 30 cm)
      were involved. RESULTS: Due to a careful calibration of films using clinical beam
      qualities, 22.8% (k = 2) overall measurement uncertainty was achieved. Calculated
      and measured PSD values agreed with an average difference of 10% +/- 7% and 9% +/
      7% for 34 test conditions performed on Siemens Artis Zee and GEMS Innova IGS
      interventional systems, respectively. Finally, RDM's 2D skin dose maps closely
      matched those registered on XR-RV3 films considering the 1-cm2 resolution. While
      RDM correctly reproduced beam overlapping due to variable tube projections, FOV,
      table positions, etc., few challenges were identified related to conversion of
      rectangular fields to square areas in the RDSR and a stair-step effect visible
      for large tube projections (>45 degrees ). CONCLUSION: The accuracy of RDM's DACS
      integrated skin dose mapping software was acceptable considering measurement
      uncertainties associated with Gafchromic(r) films.

PMID- 30098028
TI  - Use of ticagrelor alongside fibrinolytic therapy in patients with ST-segment
      elevation myocardial infarction: Practical perspectives based on data from the
      TREAT study.
AB  - Primary percutaneous coronary intervention (PCI) is the preferred reperfusion
      method in patients with ST-segment elevation myocardial infarction (STEMI). In
      patients with STEMI who cannot undergo timely primary PCI, pharmacoinvasive
      treatment is recommended, comprising immediate fibrinolytic therapy with
      subsequent coronary angiography and rescue PCI if needed. Improving clinical
      outcomes following fibrinolysis remains of great importance for the many patients
      globally for whom rapid treatment with primary PCI is not possible. For patients
      with acute coronary syndrome who underwent primary PCI, the PLATO trial
      demonstrated superior efficacy of ticagrelor relative to clopidogrel. Results in
      the predefined subgroup of patients with STEMI were consistent with the overall
      PLATO trial. Patients who received fibrinolytic therapy in the 24 hours before
      randomization were excluded from PLATO, and there is thus a lack of data on the
      safety of using ticagrelor in conjunction with fibrinolytic therapy in the first
      24 hours after STEMI. The TREAT study addresses this knowledge gap; patients with
      STEMI who had symptom onset within the previous 24 hours and had received
      fibrinolytic therapy (of whom 89.4% had also received clopidogrel) were
      randomized to treatment with ticagrelor or clopidogrel (median time between
      fibrinolysis and randomization: 11.5 hours). At 30 days, ticagrelor was found to
      be non-inferior to clopidogrel for the primary safety outcome of Thrombolysis in
      Myocardial Infarction (TIMI)-defined first major bleeding. Considering together
      the results of the PLATO and TREAT studies, initiating or switching to treatment
      with ticagrelor within the first 24 hours after STEMI in patients receiving
      fibrinolysis is reasonable.

PMID- 30098030
TI  - Overexpression of Ecm22 improves ergosterol biosynthesis in Saccharomyces
      cerevisiae.
AB  - Ergosterol biosynthesis in Saccharomyces cerevisiae is complex and the underlying
      mechanism of regulation remains unclear. To clarify the influence of
      transcriptional regulation on the ergosterol content, transcription factor Ecm22
      was overexpressed in S. cerevisiae. Results showed that the overexpression of
      ECM22 led to an increased invasive growth. Fluconazole susceptibility testing
      indicated that strains overexpressing ECM22 could grow at 20 MUg(fluconazole)  ml
      1 . By contrast, the control failed to grow at 16 MUg(fluconazole)  ml-1 . Among
      truncated ECM22 fragments, only the 1440-bp DNA fragment exerted almost the same
      impact on ergosterol content as that of the full-length gene. In a 5-l
      bioreactor, the highest ergosterol yield of the recombinant reached 32?7 mg g(dry
      cell weight) -1 , which was increased by about 20% compared with that of the
      control. In this work, a novel approach for enhancing the ergosterol production
      by overexpressing a transcription factor in S. cerevisiae was developed.

PMID- 30098032
TI  - Insular cortex lesions are not the only culprit in Takotsubo syndrome.

PMID- 30098031
TI  - Internal radiation dose estimation using multiple D-shuttle dosimeters for
      positron emission tomography (PET): A validation study using NEMA body phantom.
AB  - PURPOSE: Internal radiation dosimetry plays an important role in ensuring the
      safe use of positron emission tomography (PET) technology and is a legal
      requirement in most countries. We propose a new technique to estimate the
      internal radiation dose in PET studies by means of multiple D-shuttle dosimeters
      attached on the body surface of the patient. METHODS: Radioactivity in a source
      organ was estimated iteratively using measurements from multiple D-shuttle
      dosimeters with a maximum-likelihood expectation-maximization (MLEM) algorithm
      with dose response from a source to a D-shuttle dosimeter computed by Monte Carlo
      simulation. To validate our technique, we performed a phantom study using a
      National Electrical Manufacturers Association (NEMA) body phantom. The fillable
      compartments (torso cavity and six spheres) of the phantom were filled with 18 F
      FDG mixed with pure water using an 800:1 sphere-to-background radioactivity
      concentration ratio. The radioactivity concentrations present in the torso cavity
      and six spheres were 0.00165 MBq/mL and 1.32 MBq/mL, respectively. The initial
      radioactivities of the torso cavity and six spheres (treated as source organs)
      were 15.9 MBq (torso cavity), 34.7 MBq (37 mm sphere), 15.1 MBq (28 mm sphere),
      7.27 MBq (22 mm sphere), 3.26 MBq (17 mm sphere), 1.54 MBq (13 mm sphere), and
      0.697 MBq (10 mm sphere). Eleven D-shuttle dosimeters were attached to the NEMA
      body phantom surface to obtain information on body surface dose and a
      mathematical NEMA body phantom has been modeled in the Heavy Ion Transport Code
      System (PHITS) Monte Carlo simulation code. RESULTS: Radioactivity was estimated
      in 2 min intervals over a 110-min total dose time using our proposed technique. A
      significant correlation (R2 = 0.992) was found between actual radioactivity and
      estimated radioactivity at every 2 min interval for each source organ. The
      estimated initial radioactivity (mean with standard deviation) was 16.5 +/- 0.311
      MBq (torso cavity), 33.0 +/- 0.624 MBq (37 mm sphere), 15.7 +/- 0.189 MBq (28 mm
      sphere), 7.11 +/- 0.738 MBq (22 mm sphere), 4.17 +/- 0.083 MBq (17 mm sphere),
      1.48 +/- 0.469 MBq (13 mm sphere), and 0.865 +/- 0.313 MBq (10 mm sphere), which
      were very close to the actual initial radioactivity measurements for each source
      organ. CONCLUSIONS: The phantom study showed that our technique worked
      successfully. This technique could be used to estimate internal radiation
      dosimetry in a clinical PET study.

PMID- 30098033
TI  - First Successful Mechanical Splint for Obstructive Sleep Apnea With an Orally
      Administrable Pharyngeal Stenting Device.
AB  - We report the case of obstructive sleep apnea in a 19-year-old, otherwise healthy
      male presenting with persistent daytime sleepiness and nonrestorative sleep after
      velo- and uvuloplasty. An individually tailored prototype of an orally inserted
      pharyngeal stenting device was proposed in the framework of a first clinical
      feasibility trial. The noninvasive, easily self-administered device is mounted on
      a simple inferior dental guard. Baseline total apnea-hypopnea index (AHI) was
      15.5 and 24.4 per hour of rapid eye movement (REM) sleep. With the device, total
      AHI dropped to 6.7 per hour (56.8% reduction) and 1.4 per hour of REM (94.3%
      reduction). Recorded sleep efficiency during treatment was excellent at 96.5%.

PMID- 30098035
TI  - Upper Airway Stimulation in Patients With Obstructive Sleep Apnea and an Elevated
      Body Mass Index: A Multi-institutional Review.
AB  - OBJECTIVES/HYPOTHESIS: An elevated body mass index (BMI) influences the severity
      of disease and treatment options utilized for obstructive sleep apnea (OSA). With
      this study, we aim to evaluate a cohort of patients undergoing upper airway
      stimulation (UAS) for treatment of OSA and assess the impact of BMI on surgical
      and quality of life outcomes. METHODS: We designed a case-control, retrospective
      review, of all patients undergoing UAS at two academic institutions between 2014
      and 2017. We compare those with an elevated BMI to those without. We included
      patients with moderate-severe OSA, who were unable to tolerate therapy with
      continuous positive airway pressure (CPAP), were treated with UAS, and had a
      postoperative sleep study performed. We evaluated postoperative sleep study data
      including apnea-hypopnea index (AHI), O2 desaturation nadir, rate of cure, and
      rate of success in those with an elevated BMI to those without an elevated BMI.
      Success was defined as a drop in the postoperative AHI by 50% compared to the
      preoperative value and to less than 20. We also assessed daytime sleepiness using
      the Epworth Sleepiness Scale. RESULTS: When defining an elevated BMI as greater
      than 32, we found no difference between elevated and nonelevated BMI cohorts in
      postoperative AHI, O2 desaturation nadir, daytime sleepiness, rate of surgical
      success, or rate of cure. CONCLUSIONS: Patients with obstructive sleep apnea,
      unable to tolerate CPAP, and with an elevated BMI can be successfully treated
      with upper airway stimulation therapy. LEVEL OF EVIDENCE: 3. Laryngoscope,
      128:2425-2428, 2018.

PMID- 30098036
TI  - Response to Association of Prolonged QTc Interval With Takotsubo Cardiomyopathy:
      A Neurocardiac Syndrome Inside the Mystery of the Insula of Reil.

PMID- 30098037
TI  - The anatomy of transanal minimally invasive surgery: Perineal distances and
      transanal angles.
AB  - BACKGROUND: The recent interest in transanal, minimally invasive surgery has
      highlighted the importance of an in depth understanding of this complex region.
      We applied data from an anatomical study of the perineum to the concept of
      transanal minimally invasive surgery with the aim to describe more accurately
      anatomy relevant to this surgical technique. METHODS: A consecutive series of
      adult patients undergoing colonoscopy were approached for consent to measure
      dimensions and angles of the perineum before the examination. Distances from the
      posterior margin of the anus to the coccyx, and the anterior margin of the anus
      to the posterior edge of the scrotum or introitus were measured. Then, using a
      pediatric proctoscope and a protractor the anoperineal angle and the recto
      perineal angles were measured. The anorectal angle was derived from these
      measurements. Data is described using means and standard deviations. RESULTS:
      Measurements were obtained from 106 patients undergoing elective colonoscopy for
      average risk screening with no history of defecatory disorder. Posterior perineal
      length was similar in both sexes (4.5cm + 0.9 in women and 4.6cm +0.7 in men) but
      the anterior perineum was significantly shorter in women (2.5 + 0.8). The mean
      anoperineal angle was 93 degrees (+9), and mean rectoperineal angle was 73
      degrees (+9). These angles varied significantly between the sexes. The mean
      anorectal angle (derived) was 160 degrees (+9), and did not differ significantly
      between the sexes. There was no correlation between the posterior perineal length
      and ano perineal, recto perineal or anorectal angles. LIMITATIONS: Small sample
      size CONCLUSIONS: Anoperineal and recto perineal differ significantly between the
      sexes. Surgeons using transanal minimally invasive surgical techniques should
      expect to alter the alignment of their dissection accordingly. This study shows
      the magnitude of the differences that can exist. This article is protected by
      copyright. All rights reserved.

PMID- 30098034
TI  - Association of Healthcare Plan with atrial fibrillation prescription patterns.
AB  - BACKGROUND: Atrial fibrillation (AF) is treated by many types of physician
      specialists, including primary care physicians (PCPs). Health plans have
      different policies for how patients encounter these providers, and these may
      affect selection of AF treatment strategy. HYPOTHESIS: We hypothesized that
      healthcare plans with PCP-gatekeeping to specialist access may be associated with
      different pharmacologic treatments for AF. METHODS: We performed a retrospective
      cohort study using a commercial pharmaceutical claims database. We utilized
      logistic regression models to compare odds of prescription of oral anticoagulant
      (OAC), non-vitamin K-dependent oral anticoagulant (NOAC), rate control, and
      rhythm control medications used to treat AF between patients with PCP-gated
      healthcare plans (eg, HMO, EPO, POS) and patients with non-PCP-gated healthcare
      plans (eg, PPO, CHDP, HDHP, comprehensive) between 2007 and 2012. We also
      calculated median time to receipt of therapy within 90 days of index AF
      diagnosis. RESULTS: We found similar odds of OAC prescription at 90 days
      following new AF diagnosis in patients with PCP-gated plans compared to those
      with non-PCP-gated plans (OR: OAC 1.01, P = 0.84; warfarin 1.05, P = 0.08).
      Relative odds were similar for rate control (1.17, P < 0.01) and rhythm control
      agents (0.93, P = 0.03). However, PCP-gated plan patients had slightly lower
      likelihood of being prescribed NOACs (0.82, P = 0.001) than non-gated plan
      patients. Elapsed time until receipt of medication was similar between PCP-gated
      and non-gated groups across drug classes. CONCLUSIONS: Pharmaceutical claims data
      do not suggest that PCP-gatekeeping by healthcare plans is a structural barrier
      to AF therapy, although it was associated with lower use of NOACs.

PMID- 30098038
TI  - Towards context-sensitive CT imaging - organ-specific image formation for single
      (SECT) and dual energy computed tomography (DECT).
AB  - PURPOSE: The purpose of this study was to establish a novel paradigm to
      facilitate radiologists' workflow - combining mutually exclusive CT image
      properties that emerge from different reconstructions, display settings and organ
      dependent spectral evaluation methods into a single context-sensitive imaging by
      exploiting prior anatomical information. METHODS: The CT dataset is segmented and
      classified into different organs, for example, the liver, left and right kidney,
      spleen, aorta, and left and right lung as well as into the tissue types bone,
      fat, soft tissue, and vessels using a cascaded three-dimensional fully
      convolutional neural network (CNN) consisting of two successive 3D U-nets. The
      binary organ and tissue masks are transformed to tissue-related weighting
      coefficients that are used to allow individual organ-specific parameter settings
      in each anatomical region. Exploiting the prior knowledge, we develop a novel
      paradigm of a context-sensitive (CS) CT imaging consisting of a prior-based
      spatial resolution (CSR), display (CSD), and dual energy evaluation (CSDE). The
      CSR locally emphasizes desired image properties. On a per-voxel basis, the
      reconstruction most suitable for the organ, tissue type, and clinical indication
      is chosen automatically. Furthermore, an organ-specific windowing and display
      method is introduced that aims at providing superior image visualization. The
      CSDE analysis allows to simultaneously evaluate multiple organs and to show organ
      specific DE overlays wherever appropriate. The ROIs that are required for a
      patient-specific calibration of the algorithms are automatically placed into the
      corresponding anatomical structures. The DE applications are selected and only
      applied to the specific organs based on the prior knowledge. The approach is
      evaluated using patient data acquired with a dual source CT system. The final CS
      images simultaneously link the indication-specific advantages of different
      parameter settings and result in images combining tissue-related desired image
      properties. RESULTS: A comparison with conventionally reconstructed images
      reveals an improved spatial resolution in highly attenuating objects and in air
      while the compound image maintains a low noise level in soft tissue. Furthermore,
      the tissue-related weighting coefficients allow for the combination of varying
      settings into one novel image display. We are, in principle, able to automate and
      standardize the spectral analysis of the DE data using prior anatomical
      information. Each tissue type is evaluated with its corresponding DE application
      simultaneously. CONCLUSION: This work provides a proof of concept of CS imaging.
      Since radiologists are not aware of the presented method and the tool is not yet
      implemented in everyday clinical practice, a comprehensive clinical evaluation in
      a large cohort might be topic of future research. Nonetheless, the presented
      method has potential to facilitate workflow in clinical routine and could
      potentially improve diagnostic accuracy by improving sensitivity for incidental
      findings. It is a potential step toward the presentation of evermore increasingly
      complex information in CT and toward improving the radiologists workflow
      significantly since dealing with multiple CT reconstructions may no longer be
      necessary. The method can be readily generalized to multienergy data and also to
      other modalities.

PMID- 30098040
TI  - Metabolism of steroids by cytochrome P450 2C9 variants.
AB  - CYP2C9 is a human microsomal cytochrome P450c (CYP). Much variation in CYP2C9
      levels and activity can be attributed to polymorphisms of this gene. Wild-type
      CYP2C9 and ten mutants were co-expressed with NADPH-cytochrome P450 reductase in
      Escherichia coli. The hydroxylase activities toward steroids were examined.
      CYP2C9.2, CYP2C9.3, CYP2C9.4, CYP2C9.16, CYP2C9.28, CYP2C9.48 and CYP2C9.52 had
      higher testosterone 6beta-hydroxylation than CYP2C9.1. CYP2C9.4 showed higher
      progesterone 6beta-hydroxylation activity than CYP2C9.1. CYP2C9.28 and CYP2C9.48
      showed higher progesterone 11alpha-hydroxylation activity than CYP2C9.1.
      CYP2C9.48 showed higher progesterone 16alpha-hydroxylation activity than
      CYP2C9.1. CYP2C9.2, CYP2C9.3, CYP2C9.16 and CYP2C9.30 had higher estrone 16alpha
      hydroxylation activity than CYP2C9.1. CYP2C9.3 had higher estrone 11alpha
      hydroxylation activity than CYP2C9.1. CYP2C9.39 and CYP2C9.57 showed similar
      activities to CYP2C9.1. These results indicate that the substrate specificity of
      CYP2C9.39 and CYP2C9.57 was not changed, but CYP2C9.2, CYP2C9.3, CYP2C9.4,
      CYP2C9.16, CYP2C9.28, CYP2C9.30, CYP2C9.48 and CYP2C9.52 showed different
      hydroxylation activities toward steroids compared with CYP2C9.1.

PMID- 30098039
TI  - Trigger Reduction Prior to Systemic Drugs for Neurogenic Chronic Cough.
AB  - OBJECTIVE/HYPOTHESIS: Neurogenic chronic cough typically presents as a postviral
      chronic cough, often with paroxysms of coughing preceded by a tickle sensation
      with multiple triggers and often recalcitrant to multiple treatments for reflux
      disease, sinus disease, and asthma. Current treatment uses neuromodulating agents
      with moderate success. Post nasal drainage and laryngopharyngeal reflux can be
      triggers in the setting of laryngopharyngeal hypersensitivity. Treatment will
      focus on trigger reduction using nasal toilet and a dietary regimen for
      laryngopharyngeal reflux. STUDY DESIGN: Systematic review of retrospective cohort
      studies METHODS: One-year retrospective review of new patients with cough (R05.0)
      excluding asthma, proton pump inhibitor response, and sinus or pulmonary disease.
      Cough severity index (CSI) and reflux symptom index (RSI) were evaluated
      initially and 6 weeks after trigger-reduction treatment using nasal saline
      irrigation, nasal steroids, nasal antihistamines, and a plant-based diet with
      alkaline water. RESULTS: Of 119 patients, 29 met the criteria. Using the six
      point reduction (improvement) in RSI as an accepted response, 20 of 29 patients
      (68.9%, P = .0014) experienced a clinical response. Using reduction in RSI and
      CSI as a continuous variable to assess response, patients experienced a 10 (95%
      confidence interval [CI]: 6.75-13.2) and 10.9 (95% CI: 7.4-14.3) mean point
      reduction, respectively. The mean percent reduction in RSI following 6 weeks of
      treatment was 54.7% (95% CI: 41.5-68.0; P = .0001). These patients experienced a
      59.8% (95% CI: 43.4-76.2; P = .0001) reduction in CSI. CONCLUSIONS: A trigger
      reduction approach using nasal toilet and a plant-based diet in patients with
      neurogenic chronic cough prior to the initiation of systemic neuromodulating
      medications should be considered. LEVEL OF EVIDENCE: 4. Laryngoscope, 1-5, 2018.

PMID- 30098041
TI  - An investigation of left-right vocal fold symmetry in rheological and
      histological properties.
AB  - OBJECTIVES: The primary objective was to investigate the left-right vocal fold
      symmetry in rheological and histological properties using a rabbit model. The
      other objective was to develop statistical models for the comparison of
      rheological properties between paired vocal folds. METHODS: Viscoelastic shear
      properties of six pairs of vocal fold lamina propria specimens were measured over
      a frequency range of 1 to 250 Hz by a linear, controlled-strain, simple-shear
      rheometer. The rheological data of the left and right vocal folds was
      statistically compared using the mixed-effects model approach. Six additional
      rabbit larynges were histologically analyzed for left-right symmetry in
      distribution patterns and relative densities of major extracellular matrix
      constituents. RESULTS: There were no significant differences in elastic shear
      modulus (P = 0.1069) and dynamic viscosity (P = 0.944) of the lamina propria
      between the two vocal folds of the same larynx. Left-right vocal fold symmetry in
      densities and distribution patterns of the key molecular constituents was also
      demonstrated in histological results. CONCLUSION: By showing that the left and
      right vocal folds were rheologically and histologically symmetrical in rabbit,
      this study validated an underlying assumption made in many previous reports.
      Statistical models for the analysis of hierarchically correlated left-right vocal
      fold rheological data were also presented. LEVEL OF EVIDENCE: NA. Laryngoscope,
      128:E359-E364, 2018.

PMID- 30098042
TI  - Single- and multiple-dose pharmacokinetics and safety of pimodivir, a novel, non
      nucleoside polymerase basic protein 2 subunit inhibitor of the influenza A virus
      polymerase complex, and interaction with oseltamivir: a Phase 1 open-label study
      in healthy volunteers.
AB  - AIMS: The aim of this study was to evaluate the drug-drug interaction between
      pimodivir, a novel, non-nucleoside polymerase basic protein 2 (PB2) subunit
      inhibitor of the influenza A virus polymerase complex, and oseltamivir, to assess
      the feasibility of this combination therapy. Furthermore, single- and multiple
      dose pharmacokinetics and safety of pimodivir in healthy volunteers were
      assessed. METHODS: In Part 1 of this open-label Phase 1 study, healthy volunteers
      (n = 18) were randomized to one of six cross-over treatment sequences, each
      comprising administration of oseltamivir 75 mg or pimodivir 600 mg or combination
      thereof twice daily on Days 1-4, followed by a single morning dose on Day 5.
      Between each treatment session, there was a minimum 5-day washout period. In Part
      2, healthy volunteers (n = 16) randomly received pimodivir 600 mg or placebo
      (3:1) twice daily on Days 1-9, followed by a single morning dose on Day 10.
      Pharmacokinetics of pimodivir, oseltamivir and oseltamivir carboxylate, and
      safety were assessed. RESULTS: In Part 1, co-administration of pimodivir with
      oseltamivir increased the Cmax of pimodivir by 31% (90% CI: 0.92-1.85) with no
      change in Cmin or AUC12h . Pimodivir had no effect on oseltamivir or oseltamivir
      carboxylate pharmacokinetics. In Part 2, after single- and multiple-dose
      administration of pimodivir, there was a 1.2- and 1.8-fold increase in Cmax and
      AUC12h , respectively, between Day 1 and Day 10. The most frequently reported
      treatment-emergent adverse event was diarrhoea (n = 7 each in Part 1 and 2).
      CONCLUSION: Combination treatment with pimodivir and oseltamivir in healthy
      volunteers showed no clinically relevant drug-drug interactions. No safety
      concerns were identified with pimodivir 600 mg twice daily alone or in
      combination with oseltamivir 75 mg twice daily.

PMID- 30098043
TI  - Analysis of Risk Factors for Unplanned Reoperation Following Free Flap Surgery of
      the Head and Neck.
AB  - OBJECTIVES/HYPOTHESIS: Evaluate risk factors for unplanned reoperation following
      free flap surgery of the head and neck. STUDY DESIGN: Retrospective database
      review. METHODS: The National Surgical Quality Improvement Program database was
      queried for free flap surgeries of the head and neck between 2010 and 2014.
      Bivariate and multivariate analyses were performed to compare perioperative
      variables and postoperative complications in patients with and without unplanned
      reoperation. RESULTS: A total of 1,796 patients were identified, with an overall
      unplanned reoperation rate of 20.0% (n = 359) within 30 days after surgery. Upon
      multivariate analysis, independent preoperative risk factors for unplanned
      reoperation include smoking (odds ratio [OR]: 1.389, 95% confidence interval
      [CI]: 1.042-1.850), hypertension (OR: 1.443, 95% CI: 1.096-1.901), and prior open
      wound/wound infection (OR: 1.675, 95% CI: 1.123-2.499). Intraoperative risk
      factors include prolonged operative time (OR: 1.045, 95% CI: 1.021-1.070).
      Surgical site infection (OR: 6.518, 95% CI: 2.728-15.574), wound disruption (OR:
      17.034, 95% CI: 8.373-34.654), blood transfusion (OR: 1.561, 95% CI: 1.062
      2.296), and ventilation > 48 hours (OR: 3.626, 95% CI: 1.955-6.723) were
      significant postoperative predictors of unplanned reoperation. CONCLUSIONS: In
      patients with free flap surgeries of the head and neck, preoperative smoking,
      hypertension, and prior open wound/wound infection, along with prolonged
      operative time, are risk factors for 30-day unplanned reoperation. In addition,
      postoperative surgical site infection, wound disruption, blood transfusion, and
      ventilation >48 hours are independently associated with unplanned reoperation.
      LEVEL OF EVIDENCE: 4. Laryngoscope, 1-6, 2018.

PMID- 30098045
TI  - Initial and Long-term Retention of Robotic Technical Skills in an Otolaryngology
      Residency Program.
AB  - OBJECTIVES/HYPOTHESIS: To objectively assess the initial and long-term retention
      of robotic surgical skills of otolaryngology residents. STUDY DESIGN: This study
      was performed in an academic otolaryngology residency training program. Between
      October 2015 and November 2016, residents were invited to complete a prospective,
      multiphase robotic surgical skills training course: 1) online da Vinci Surgical
      System Assessment and didactic, 2) faculty-supervised robotic simulator training,
      3) robotic docking and draping training, 4) robotic dry-lab exercises. To
      optimize surgical skill retention, the training laboratory was repeated 2 weeks
      after the initial training session. METHODS: Twenty otolaryngology residents were
      included. Primary outcome was measured as robotic skill assessment scores on
      three tasks: camera targeting, peg board, and needle targeting. Skill assessments
      were completed prior to training, between the two training sessions, and at 1
      month and 6 months after training. Residents were also asked to complete a self
      assessment questionnaire. RESULTS: Camera targeting scores were improved at
      midtraining (P < .001) and 1-month posttraining (P = .010). Peg board scores were
      improved at 1 month training (P = .043). Needle targeting scores were improved at
      midtraining (P = .002), 1 month (P = .002), and 6 months posttraining (P < .001).
      Resident self-assessment scores demonstrating comfort with using the robotic
      console (P < .01) and docking/draping (P < .01) improved significantly following
      the training. CONCLUSIONS: Following a multiphase robotic training program,
      otolaryngology residents demonstrated significant, objective skill acquisition
      and retention at 1 month and 6 months follow-up. Although the proposed training
      strategy may be considered an important step in otolaryngology residency
      training, additional innovations are being designed toward a formal robotic
      training curriculum. LEVEL OF EVIDENCE: NA.

PMID- 30098044
TI  - Abdominal DCE-MRI reconstruction with deformable motion correction for liver
      perfusion quantification.
AB  - PURPOSE: Abdominal dynamic contrast-enhanced (DCE) MRI suffers from motion
      induced artifacts that can blur images and distort contrast-agent uptake curves.
      For liver perfusion analysis, image reconstruction with rigid-body motion
      correction (RMC) can restore distorted portal-venous input functions (PVIF) to
      higher peak amplitudes. However, RMC cannot correct for liver deformation during
      breathing. We present a reconstruction algorithm with deformable motion
      correction (DMC) that enables correction of breathing-induced deformation in the
      whole abdomen. METHODS: Raw data from a golden-angle stack-of-stars gradient-echo
      sequence were collected for 54 DCE-MRI examinations of 31 patients. For each
      examination, a respiratory motion signal was extracted from the data and used to
      reconstruct 21 breathing states from inhale to exhale. The states were aligned
      with deformable image registration to the end-exhale state. Resulting deformation
      fields were used to correct back-projection images before reconstruction with
      view sharing. Images with DMC were compared to uncorrected images and images with
      RMC. RESULTS: DMC significantly increased the PVIF peak amplitude compared to
      uncorrected images (P << 0.01, mean increase: 8%) but not compared to RMC. The
      increased PVIF peak amplitude significantly decreased estimated portal-venous
      perfusion in the liver (P << 0.01, mean decrease: 8 ml/(100 ml.min)). DMC also
      removed artifacts in perfusion maps at the liver edge and reduced blurring of
      liver tumors for some patients. CONCLUSIONS: DCE-MRI reconstruction with DMC can
      restore motion-distorted uptake curves in the abdomen and remove motion artifacts
      from reconstructed images and parameter maps but does not significantly improve
      perfusion quantification in the liver compared to RMC.

PMID- 30098046
TI  - Clinical Implications of Tumor-Associated Tissue Eosinophilia in Tongue Squamous
      Cell Carcinoma.
AB  - OBJECTIVES/HYPOTHESIS: The role of tumor-associated tissue eosinophilia (TATE) in
      oral cavity cancer remains quite controversial. This study investigated the
      potential role of TATE in tongue squamous cell carcinoma (TSCC). STUDY DESIGN:
      Retrospective case series. METHODS: This study retrospectively enrolled 259
      consecutive TSCC patients who underwent surgery between July 2004 and December
      2015. Histopathological examinations for TATE in TSCC tumors were reviewed, and
      the association of TATE with different clinicopathological factors was evaluated.
      A nomogram was generated based on several major clinicopathological factors and
      TATE to improve the accuracy of prognostic prediction. RESULTS: Higher levels of
      TATE were significantly associated with male sex, alcohol consumption, cigarette
      smoking, higher pT classification, advanced disease stage, and tumor depth (P =
      .006, .003, .024, .041, .013 and .006, respectively). Our results indicated that
      extranodal extension, cell differentiation, and TATE were independent predictors
      of overall survival (P < .001, .004, and .032, respectively) and disease-free
      survival (P < .001, .012, and .013, respectively). TATE levels significantly
      correlated with circulating eosinophils (r = 0.139, P = .040), and the c-index of
      our nomogram foroverall survival was 0.786, which demonstrates better accuracy in
      prognosis prediction than the TNM stage only (c-index = 0.738). CONCLUSIONS:
      Higher levels of TATE were associated with several clinicopathological factors
      and poorer survival rates, and a nomogram incorporating TATE levels may
      strengthen the prediction accuracy of prognosis in TSCC patients. LEVEL OF
      EVIDENCE: 4.

PMID- 30098047
TI  - Fluorescent Reporter Mice for Nerve Guidance Conduit Assessment: A High
      Throughput in vivo Model.
AB  - OBJECTIVE: Use of cell culture and conventional in vivo mammalian models to
      assess nerve regeneration across guidance conduits is resource-intensive. Herein
      we describe a high-throughput platform utilizing transgenic mice for stain-free
      axon visualization paired with rapid cryosection techniques for low-cost
      screening of novel bioengineered nerve guidance conduit performance. METHODS:
      Interposition repair of sciatic nerve transection in mice expressing yellow
      fluorescent protein in peripheral neurons (Thy1.2 YFP-16) was performed with
      various bioengineered neural conduit compositions using a rapid sutureless
      entubulation technique under isoflurane anesthesia. Axonal ingrowth was assessed
      at 3 and 6 weeks using epifluorescent microscopy following cryosectioning.
      RESULTS: Mean procedure time (incision-to-closure) was less than 21/2 minutes.
      Direct operational costs of a 3-week experiment was calculated at $21.47 per
      animal. Tissue processing steps were minimized to aldehyde fixation,
      cryoprotection and sectioning, and rapid fluorescent dye staining for conduit
      visualization. Fluorescent microscopy readily resolved robust axonal sprouting at
      3 weeks, with clear elucidation of ingrowth-permissive, semipermissive, or
      restrictive nerve guidance conduit environments. CONCLUSION: A rapid and cost
      efficient in vivo platform for screening of nerve guidance conduit performance
      has been described. LEVEL OF EVIDENCE: NA. Laryngoscope, E392-E392, 2018.

PMID- 30098048
TI  - Endonasal anatomy of the olfactory neural network: Surgical implications.
AB  - OBJECTIVES/HYPOTHESIS: Define the anatomic distribution of the olfactory
      filaments within specific mucosal regions of the nasal cavity. STUDY DESIGN:
      Cadaveric study. METHODS: Seventeen cadaveric specimens (34 sides) were dissected
      to study the anatomical distribution and density of olfactory fila within
      different regions of the nasal cavity. Olfactory fila were dissected retrogradely
      to their point of entry into the anterior cranial fossa through the cribriform
      plate. Anatomic relationships among various components of the olfactory system
      and their corresponding arterial supply were determined subjectively. RESULTS:
      The highest density of olfactory fila was found at the mucosa of the ethmoid roof
      and superior turbinates. Olfactory fila were found at regions not previously
      considered to be part of the olfactory system: lateral wall of the nose,
      ethmoidal bullae, and between the os sphenoidale and arc of the posterior choana.
      Furthermore, at the septum, 20% of the olfactory fila crossed contralaterally
      before exiting the nose. The anterior ethmoidal arteries were the primary blood
      supply to the olfactory epithelium. CONCLUSIONS: This study suggests that
      olfactory filaments extend beyond previously established boundaries. These
      findings may have clinical implications regarding oncologic resections and could
      serve as the foundation for the development of techniques that better preserve
      olfactory function. LEVEL OF EVIDENCE: NA Laryngoscope, 2473-2477, 2018.

PMID- 30098049
TI  - Anticholinergic exposure and cognitive decline in older adults: effect of
      anticholinergic exposure definitions in a 3-year analysis of the multidomain
      Alzheimer preventive trial (MAPT) study.
AB  - AIM: The aim of the present study was to assess the association between
      anticholinergic (atropinic) burden and cognitive decline in older adults over the
      course of 3 years. METHODS: We used data from Multidomain Alzheimer Preventive
      Trial (MAPT) study participants aged >=70 years and at risk of cognitive decline.
      Cognitive function was assessed with a composite score [Mini-Mental State
      Examination (MMSE) orientation, Free and Cued Selective Reminding Test, Category
      Naming Test, Digit Symbol Substitution Test] at 12, 24 and 36 months.
      Participants declining by more than 0.236 points on the composite score
      (representing the lowest quintile of 1-year cognitive change) during any 1-year
      period were considered to have undergone cognitive decline. Anticholinergic
      exposure was defined by four methods for each of four anticholinergic scales
      (Anticholinergic Drug Scale, Anticholinergic Cognitive Burden, Anticholinergic
      Risk Scale, the Duran list). The association between cognitive decline and time
      varying anticholinergic exposure [primary analysis using the Duran list and
      maximal anticholinergic score (0, 1 or 3)] was assessed using Cox proportional
      hazards models. Other cognitive decline definitions were used in sensitivity
      analyses. RESULTS: At baseline, among 1396 patients included, 7.4-23.5% were
      exposed to anticholinergic agents, depending on the anticholinergic scale used.
      Sixty-four per cent of participants experienced cognitive decline during follow
      up. Regardless of the anticholinergic scale/exposure measurement used, no
      significant association was observed with cognitive decline {primary analysis:
      compared with non-anticholinergic agent users, hazard ratio [HR] = 1.14 [95%
      confidence interval (CI) = 0.95, 1.38] for anticholinergic score = 1; HR = 0.92
      [95% CI = 0.65, 1.30] for score = 3}. Results were stable in sensitivity
      analyses. CONCLUSION: We found no significant association between anticholinergic
      exposure and cognitive decline in older adults using anticholinergic scales and
      definitions of exposure.

PMID- 30098051
TI  - The Relationships Between the Nasolacrimal Duct and the Anterior Wall of the
      Maxillary Sinus.
AB  - OBJECTIVES/HYPOTHESIS: To examine the anatomic relationships between the lower
      end opening into the inferior meatus of the bony nasolacrimal duct (NLD) and the
      anterior wall of the maxillary sinus. STUDY DESIGN: Anatomical investigation.
      METHODS: A total of 206 individuals were recruited for detailed anatomic
      investigation of the lower end of the bony NLD and their relation to the anterior
      wall of the maxillary sinus by high-resolution computed tomography (HRCT)
      imaging. The observed features were classified as either a fusion type or
      separation type, according to the HRCT images. Additionally, the angle between
      the anterior and medial wall of the maxillary sinus was classified as either an
      anterior mode or lateral mode. RESULTS: The NLD anatomical fusion type was found
      in 40.05% and the separation type in 59.95% of the HRCT imaging scans available.
      The anterior mode of angle between the anterior and medial wall of the maxillary
      sinus was present in 64.1% of the images, and the lateral mode in 35.9% of the
      images. In 165 cases of anatomical fusion, the anterior mode of angle was present
      in 15.8% and the lateral mode in 84.2% of cases. In 247 cases of anatomical
      separation, the anterior mode was present in 97.2% and the lateral mode in 2.8%
      of cases. CONCLUSIONS: The surgical anatomy of the lower end of the bony NLD and
      anterior wall of the maxillary sinus displays varied relationships. Preoperative
      use of HRCT and an awareness of the particular type of anatomical feature present
      are likely to aid in planning and performing successful endoscopic medial
      maxillectomy. LEVEL OF EVIDENCE: 4.

PMID- 30098052
TI  - The risk of graft loss 5 years after kidney transplantation is increased if cold
      ischemia time exceeds 14 hours.
AB  - BACKGROUND: The state of the evidence is unclear regarding the impact of cold
      ischemia time (CIT) on the outcome of kidney transplantation. The aim of this
      study was to investigate the effect of CIT on the short- and long-term function
      of kidneys transplanted at the Sahlgrenska University Hospital in 2007-2009 from
      donors after brain death (DBDs). METHODS: This study was designed as a
      retrospective analysis of data from local and national transplantation registers.
      The study endpoints were as follows: delayed graft function (DGF), primary
      nonfunction (PNF), biopsy-proven acute rejection (BPAR), serum creatinine (S
      creatinine) level at discharge, days of hospitalization after transplantation,
      and graft survival at 5 years post-transplantation. Adjusted regression analyses
      were used to determine causal relationships with CIT. A further aim was to
      estimate a threshold for CIT by analyzing event rates and coordinates of the
      receiver-operated characteristic (ROC) curve. RESULTS: There was a causal
      relationship between CIT as a continuous variable and the following endpoints:
      graft survival at 5 years post-transplantation, though this was not significant
      (hazard ratio (HR) 1.07, P = 0.057), DGF (odds ratio (OR) 1.09, P = 0.03) and S
      creatinine (P = 0.003). In our material, the risk for impaired outcome was higher
      with longer CIT. We were therefore able to estimate a threshold value for CIT,
      set to 14 hours for both graft survival at 5 years post-transplantation and DGF.
      This was proved with significance by analyzing both event rates and the
      coordinates of the ROC curve. The risk of graft loss increased, with HR 2.3 (P =
      0.023), when comparing a CIT cutoff of >=14 hours with CIT < 14 hours. Delayed
      graft function increased, with an OR of 2.6 (P = 0.001). CONCLUSION: Our study
      confirms that, in this patient material, longer CIT was associated with increased
      risk for both impaired graft survival and incidence of DGF. We estimated a
      threshold for CIT of 14 hours.

PMID- 30098053
TI  - Racial disparity in kidney transplant survival relates to late rejection and is
      independent of steroid withdrawal.
AB  - Black kidney transplant recipients have more acute rejection (AR) and inferior
      graft survival. We sought to determine whether early steroid withdrawal (ESW) had
      an impact on AR and death-censored graft loss (DCGL) in blacks. From 2006 to
      2012, AR and graft survival were analyzed in 483 kidney recipients (208 black and
      275 non-black). Rates of ESW were similar between blacks (65%) and non-blacks
      (67%). AR was defined as early (<=3 months) or late (>3 months). The impact of
      black race, early AR, and late AR on death-censored graft failure was analyzed
      using univariate and multivariate Cox models. Blacks had greater dialysis
      vintage, more deceased donor transplants, and less HLA matching, yet rates of
      early AR were comparable between blacks and non-blacks. However, black race was a
      risk factor for late AR (HR: 3.48 (95% CI: 1.87-6.47)) Blacks had a greater rate
      of DCGL, partially driven by late AR (HR with late AR: 5.6; 95% CI: 3.3-9.3). ESW
      had no significant interaction with black race for risk of early AR, late AR, or
      DCGL. Independent of ESW, black kidney recipients had a higher rate of late AR
      after kidney transplantation. Late AR was highly predictive of DCGL and
      contributed to inferior graft survival in blacks.

PMID- 30098050
TI  - Regularization strategies in statistical image reconstruction of low-dose x-ray
      CT: A review.
AB  - Statistical image reconstruction (SIR) methods have shown potential to
      substantially improve the image quality of low-dose x-ray computed tomography
      (CT) as compared to the conventional filtered back-projection (FBP) method.
      According to the maximum a posteriori (MAP) estimation, the SIR methods are
      typically formulated by an objective function consisting of two terms: (a) a data
      fidelity term that models imaging geometry and physical detection processes in
      projection data acquisition, and (b) a regularization term that reflects prior
      knowledge or expectations of the characteristics of the to-be-reconstructed
      image. SIR desires accurate system modeling of data acquisition, while the
      regularization term also has a strong influence on the quality of reconstructed
      images. A variety of regularization strategies have been proposed for SIR in the
      past decades, based on different assumptions, models, and prior knowledge. In
      this paper, we review the conceptual and mathematical bases of these
      regularization strategies and briefly illustrate their efficacies in SIR of low
      dose CT.

PMID- 30098056
TI  - Gene alterations and expression spectrum of SPATA33 in nonobstructive azoospermic
      Iranian men.
AB  - Genetic abnormalities have been considered a significant cause of male
      infertility. Increased expression of SPATA33 during the first wave of
      spermatogenesis indicates its possible association with the meiotic process. The
      aim of the current study was to investigate the genetic variations in the SPATA33
      gene and its expression in patients with nonobstructive azoospermia (NOA). A
      total of 100 Iranian NOA men with idiopathic infertility were taken as the case
      group. The control group comprised 100 fertile men who had at least one child.
      The presence of nucleotide variations was analyzed in both groups using the
      standard polymerase chain reaction (PCR) sequencing technique. For mRNA and
      protein expression studies, testicular biopsy specimens from 27 patients were
      subdivided into three groups: nine obstructive azoospermic patients with
      hypospermatogenesis as control; nine maturation arrest (MA) and nine Sertoli cell
      only syndromes (SCOS) as case groups. The expression of SPATA33 at both mRNA and
      protein levels was compared among these three groups using the reverse
      transcription PCR technique, the realtime-PCR technique, and
      immunohistochemistry. Mutation analysis of the SPATA33 gene revealed five
      nucleotide changes among the population studied. All but one showed no
      significant differences between the groups. The genotype distributions of
      rs112536073A > T in the transcription factor binding site region with
      heterozygote and homozygote genotypes were significantly different ( p < 0.05)
      between the two groups. More heterozygotes of this polymorphism were observed in
      patients, whereas more homozygotes were detected in controls. Accordingly, the
      current study illustrated that alterations in SPATA33 gene, at least those found
      in this study, may not impair spermatogenesis in patients with NOA. Reduction of
      gene expression at the level of mRNA in patients with SCOS can be interpreted by
      the absence of germ cells in the testicular tissue of these patients.

PMID- 30098057
TI  - Reply to the letter by Pindado-Ortega et al.

PMID- 30098058
TI  - Reply to: S2k guideline for treatment of cutaneous lupus erythematosus-guided by
      the European Dermatology Forum (EDF) in cooperation with the European Academy of
      Dermatology and Venereology (EADV).

PMID- 30098059
TI  - 3-Mono-Substituted BINOL Phosphoric Acids as Effective Organocatalysts in Direct
      Enantioselective Friedel-Crafts-Type Alkylation of N-Unprotected alpha
      Ketiminoester.
AB  - Although BINOL-derived phosphoric acids are among the most widely used chiral
      Bronsted acid organocatalysts, their structures are mostly limited to 3,3'
      disubstituted ones and simple 3-mono-substituted ones without any polar
      functionalities on the 3-substituent have not been used in highly
      enantioselective reactions. This work reports such 3-mono-substituted analogues
      as effective organocatalysts in direct highly enantioselective Friedel-Crafts
      type alkylation of N-unprotected alpha-ketiminoester. The origin of the observed
      high enantioselectivity with the 3-mono-substituted catalyst is also discussed.

PMID- 30098054
TI  - Bile salt hydrolases: Structure and function, substrate preference, and inhibitor
      development.
AB  - The worldwide trend of limiting the use of antibiotic growth promoters (AGPs) in
      animal production creates challenges for the animal feed industry, thus
      necessitating the development of effective non-antibiotic alternatives to improve
      animal performance. Increasing evidence has shown that the growth-promoting
      effect of AGPs is highly correlated with the reduced activity of bile salt
      hydrolase (BSH, EC 3.5.1.24), an intestinal bacteria-producing enzyme that has a
      negative impact on host fat digestion and energy harvest. Therefore, BSH
      inhibitors may become novel, attractive alternatives to AGPs. Detailed knowledge
      of BSH substrate preferences and the wealth of structural data on BSHs provide a
      solid foundation for rationally tailored BSH inhibitor design. This review
      focuses on the relationship between structure and function of BSHs based on the
      crystal structure, kinetic data, molecular docking and comparative structural
      analyses. The molecular basis for BSH substrate recognition is also discussed.
      Finally, recent advances and future prospectives in the development of potent,
      safe, and cost-effective BSH inhibitors are described.

PMID- 30098055
TI  - Refining protein structures using enhanced sampling techniques with restraints
      derived from an ensemble-based model.
AB  - This paper reports a method for high-accuracy protein structural refinement,
      which is a direct extension of the method in our recent publication (Zang, J Chem
      Phys 2018; 149:072319). It combines a parallel continuous simulated tempering
      (PCST) method with a temperature-dependent restraint and a blind model selection
      scheme. In this work, a single-reference-based restraint in previous work was
      changed to an ensemble-based model (EBM), in which the non-bonded Lennard-Jones
      term for each contacting atomic pair in previous restraining potential was
      replaced by a multi-Gaussian function whose parameters are derived from an
      ensemble of structures such as the ones from various CASP participating groups.
      The purpose of EBM is to take advantage of partial "correctness" distributed
      among members of the structural ensemble. Totally 18 targets were refined from
      the refinement category of CASP10, CASP11 and CASP12. In Top-1 group, 11 out of
      18 targets had better models (greater GDT_TS scores) than the CASPR participants.
      In Top-5 group, nine out of 18 were better. Our results show that PCST-EBM method
      can considerably improve the low-accuracy structures.

PMID- 30098060
TI  - Diverse paths to hybrid incompatibility in Arabidopsis.
AB  - One of the most essential questions of biology is to understand how different
      species have evolved. Hybrid incompatibility, a phenomenon in which hybrids show
      reduced fitness in comparison with their parents, can result in reproductive
      isolation and speciation. Therefore, studying hybrid incompatibility provides an
      entry point in understanding speciation. Hybrid incompatibilities are known
      throughout taxa, and the underlying mechanisms have mystified scientists since
      the theory of evolution by means of natural selection was introduced. In plants,
      it is only in recent years that the high-throughput genetic and molecular tools
      have become available for the Arabidopsis genus, thus helping to shed light on
      the different genes and molecular and evolutionary mechanisms that underlie
      hybrid incompatibilities. In this review, we highlight the current knowledge of
      diverse mechanisms that are known to contribute to hybrid incompatibility.

PMID- 30098061
TI  - MelaNostrum: a consensus questionnaire of standardized epidemiologic and clinical
      variables for melanoma risk assessment by the melanostrum consortium.
AB  - BACKGROUND: Many melanoma observational studies have been carried out across
      different countries and geographic areas using heterogeneous assessments of
      epidemiologic risk factors and clinical variables. AIM: To develop a consensus
      questionnaire to standardize epidemiologic and clinical data collection for
      melanoma risk assessment. METHODS: We used a stepwise strategy that included:
      compilation of variables from case-control datasets collected at various centres
      of the MelaNostrum Consortium; integration of variables from published case
      control studies; consensus discussion of the collected items by MelaNostrum
      members; revision by independent experts; addition of online tools and image
      based charts; questionnaire testing across centres and generation of a final
      draft. RESULTS: We developed a core consensus questionnaire (MelanoQ) that
      includes four separate sections: A. general and demographic data; B. phenotypic
      and ultraviolet radiation exposure risk factors and lifestyle habits; C. clinical
      examination, medical and family history; and D. diagnostic data on melanoma
      (cases only). Accompanying online tools, informative tables, and image-based
      charts aid standardization. Different subsections of the questionnaire are
      designed for self-administration, patient interviews performed by a physician or
      study nurse, and data collection from medical records. CONCLUSIONS: The MelanoQ
      questionnaire is a useful tool for the collection and standardization of
      epidemiologic and clinical data across different studies, centres, cultures and
      languages. This will expedite ongoing efforts to compile high-quality data for
      pooled analyses or meta-analyses and offer a solid base for the design of
      clinical, epidemiologic and translational studies on melanoma.

PMID- 30098063
TI  - The Coming of Age in Iodane-Guided ortho-C-H Propargylation: From Insight to
      Synthetic Potential.
AB  - As early as 1991 Ochiai et al. reported that an acid-activated form of
      phenyliodine diacetate, PhI(OAc)2 , undergoes a reaction with propargyl-silanes,
      germanes and stannanes to give the ortho-propargyl iodobenzene. This formal C-H
      alkylation was proposed to take place through an unusual (even to date) iodonio
      based [3,3] rearrangement of an intermediate allenylsilane. Although this
      mechanistic principle has been invoked in related iodane-directed C-H coupling
      reaction, some underlying principles have remained unaddressed, and the reaction
      rarely employed. Herein, DFT evidence for a mechanism best described as iodine
      guided electrophilic aromatic substitution is presented. Using a newly optimized
      reaction protocol that significantly reduces the undesired reduction process, the
      potency of the method is showcased through the synthesis of >40 structurally
      diverse ortho-iodo propargyl (or allenyl) arenes.

PMID- 30098064
TI  - Influenza A virus inhibits influenza virus replication by inducing IL-37.
AB  - BACKGROUNDS: The influenza virus is one of the major pathogens that seriously
      affect human health. It can cause a strong immune response and trigger a series
      of complications. Interleukin 37 (IL-37) is a newly discovered cytokine that
      plays an important regulatory role in infection and immunity. To date, there have
      been few studies on the correlation between influenza virus infection and IL-37.
      METHODS: Serum levels of IL-37 in 115 patients with influenza A virus (IAV)
      infection and 102 healthy subjects were measured by an enzyme-linked
      immunosorbent assay (ELISA). Real-time quantitative PCR (RT-qPCR) was used to
      detect differences in IL-37 expression in peripheral blood mononuclear cells
      (PBMCs) between IAV patients and healthy subjects. IL-37 expression was measured
      in A549 cells and PBMCs infected with IAV H3N2 using ELISA and RT-qPCR. After the
      H3N2-infected A549 cells were treated with human IL-37, the concentration of
      viral RNA was determined using RT-qPCR, and the titer of influenza virus was
      determined by a hemagglutination test. RESULTS: The IL-37 levels in the sera and
      PBMCs of patients infected with IAV were higher than those of healthy subjects.
      The expression of IL-37 mRNA and protein in IAV-infected A549 cells and PBMCs was
      upregulated, and IL-37 protein was able to inhibit the replication of IAV RNA.
      CONCLUSION: IAV-induced IL-37 expression inhibits IAV replication.

PMID- 30098062
TI  - Rhodobacterales use a unique L-threonine kinase for the assembly of the
      nucleotide loop of coenzyme B12.
AB  - Several of the enzymes involved in the conversion of adenosylcobyric acid
      (AdoCby) to adenosylcobamide (AdoCba) are yet to be identified and characterized
      in some cobamide (Cba)-producing prokaryotes. Using a bioinformatics approach, we
      identified the bluE gene (locus tag RSP_0788) of Rhodobacter sphaeroides 2.4.1 as
      a putative functional homolog of the L-threonine kinase enzyme (PduX, EC
      2.7.1.177) of S. enterica. In AdoCba, (R)-1-aminopropan-2-ol O-phosphate (AP-P)
      links the nucleotide loop to the corrin ring; most known AdoCba producers derive
      AP-P from L-Thr-O-3-phosphate (L-Thr-P). Here, we show that RsBluE has L-Thr
      independent ATPase activity in vivo and in vitro. We used 31 P-NMR spectroscopy
      to show that RsBluE generates L-Thr-P at the expense of ATP and is unable to use
      L-Ser as a substrate. BluE from R. sphaeroides or Rhodobacter capsulatus restored
      AdoCba biosynthesis in S. enterica EpsilonpduX and R. sphaeroides EpsilonbluE
      mutant strains. R. sphaeroides EpsilonbluE strains exhibited a decreased pigment
      phenotype that was restored by complementation with BluE. Finally, phylogenetic
      analyses revealed that bluE was restricted to the genomes of a few
      Rhodobacterales that appear to have a preference for a specific form of Cba,
      namely Co?-(?-5,6-dimethylbenzimidazolyl-Co?-adenosylcobamide (a.k.a.
      adenosylcobalamin, AdoCbl; coenzyme B12 , CoB12 ).

PMID- 30098065
TI  - Application of phiLOV2.1 as a fluorescent marker for visualization of
      Agrobacterium effector protein translocation.
AB  - Agrobacterium tumefaciens can genetically transform plants by translocating a
      piece of oncogenic DNA, called T-DNA, into host cells. Transfer is mediated by a
      type IV secretion system (T4SS). Besides the T-DNA, which is transferred in a
      single-stranded form and at its 5' end covalently bound to VirD2, several other
      effector proteins (VirE2, VirE3, VirD5, and VirF) are translocated into the host
      cells. The fate and function of the translocated proteins inside the host cell
      are only partly known. Therefore, several studies were conducted to visualize the
      translocation of the VirE2 protein. As GFP-tagged effector proteins are unable to
      pass the T4SS, other approaches like the split GFP system were used, but these
      require specific transgenic recipient cells expressing the complementary part of
      GFP. Here, we investigated whether use can be made of the photostable variant of
      LOV, phiLOV2.1, to visualize effector protein translocation from Agrobacterium to
      non-transgenic yeast and plant cells. We were able to visualize the translocation
      of all five effector proteins, both to yeast cells, and to cells in Nicotiana
      tabacum leaves and Arabidopsis thaliana roots. Clear signals were obtained that
      are easily distinguishable from the background, even in cases in which by
      comparison the split GFP system did not generate a signal.

PMID- 30098067
TI  - Role of galectin-3 in subclinical myocardial impairment in psoriasis.
AB  - BACKGROUND: Psoriasis has been shown to increase cardiovascular risk, and a
      contributor to this might be enhanced myocardial fibrosis promoted by the disease
      associated pro-inflammatory milieu. OBJECTIVE: We sought to investigate the
      relationship of galectin-3 (Gal-3) - a recognized mediator of fibrosis with
      inflammatory activation and left ventricular (LV) systolic and diastolic function
      in patients with psoriasis. METHODS: We enrolled 102 psoriatic patients (mean
      age: 52.5 +/- 12.6 years). Sixty-five age- and sex-matched healthy subjects
      served as controls. Echocardiographic assessment of myocardial function included
      estimation of LV longitudinal systolic deformation (GLS) and diastolic indices:
      tissue e' velocity and E/e' ratio. Laboratory measurements encompassed blood Gal
      3, creatinine, glucose, insulin, CRP and erythrocyte sedimentation rate (ESR).
      RESULTS: Patients with psoriasis were characterized by elevated Gal-3 (12.3 [9.3
      13.4] vs. 6.3 [5.5-9.4] ng/mL in healthy controls, P < 0.001), ESR (17.0 [11.0
      29.0] vs. 8.5 [6.0-13.0] mm, respectively, P < 0.001) and CRP (3.1 [1.7-10.6] vs.
      1.9 [1.5-4.0] mg/L, respectively, P < 0.001), and reduced GLS (19.9 +/- 3.7 vs.
      22.0 +/- 3.0%, respectively, P < 0.001). Progressive deterioration of GLS was
      demonstrated across Gal-3 tertiles. Significant associations between GLS and age
      (beta = -0.21, P < 0.04), Gal-3 (beta = -0.27, P < 0.01), CRP (beta = -0.22, P <
      0.03), ESR (beta = -0.25, P < 0.01), waist circumference (beta = -0.22, P < 0.03)
      and waist-to-hip ratio (beta = -0.20, P < 0.05) were found. Stepwise multiple
      regression analysis revealed that the independent determinants of GLS in
      psoriatic patients were Gal-3 (beta = -0.24, P < 0.01) and ESR (beta = -0.21, P <
      0.03). Regression-based mediation analysis demonstrated that the relationship
      between ESR and GLS was partially mediated by Gal-3. CONCLUSIONS: Subclinical
      left ventricular systolic dysfunction in psoriasis, as evidenced by reduced GLS,
      is linked with the inflammatory upregulation, and enhanced profibrotic activity
      (as reflected by elevated serum Gal-3) may be involved in this process. These
      putative mechanisms may be responsible for the observed higher incidence of heart
      failure in this disease condition and should be considered as a potential target
      for preventive and therapeutic measures.

PMID- 30098068
TI  - Seed germination and dormancy traits of forbs and shrubs important for
      restoration of North American dryland ecosystems.
AB  - In degraded dryland systems, native plant community re-establishment following
      disturbance is almost exclusively carried out using seeds, but these efforts
      commonly fail. Much of this failure can be attributed to the limited
      understanding of seed dormancy and germination traits. We undertook a systematic
      classification of seed dormancy of 26 species of annual and perennial forbs and
      shrubs that represent key, dominant genera used in restoration of the Great Basin
      ecosystem in the western United States. We examined germination across a wide
      thermal profile to depict species-specific characteristics and assessed the
      potential of gibberellic acid (GA3 ) and karrikinolide (KAR1 ) to expand the
      thermal germination envelope of fresh seeds. Of the tested species, 81% produce
      seeds that are dormant at maturity. The largest proportion (62%) exhibited
      physiological (PD), followed by physical (PY, 4%), combinational (PY+PD, 4%), and
      morphophysiological (MPD, 1%) dormancy classes. The effects of chemical
      stimulants were temperature- and species-mediated. In general, mean germination
      across the thermal profile was improved by GA3 and KAR1 for 11 and five species,
      respectively. We detected a strong germination response to temperature in freshly
      collected seeds of 20 species. Temperatures below 10 degrees C limited the
      germination of all except Agoseris heterophylla, suggesting that in their dormant
      state, the majority of these species are thermally restricted. Our findings
      demonstrate the utility of dormancy classification as a foundation for
      understanding the critical regenerative traits in these ecologically important
      species and highlight their importance in restoration planning. This article is
      protected by copyright. All rights reserved.

PMID- 30098066
TI  - Combined inhibition of MEK and PI3K pathways overcomes acquired resistance to
      EGFR-TKIs in non-small cell lung cancer.
AB  - Compensatory activation of the signal transduction pathways is one of the major
      obstacles for the targeted therapy of non-small cell lung cancer (NSCLC). Herein,
      we present the therapeutic strategy of combined targeted therapy against the MEK
      and phosphoinositide-3 kinase (PI3K) pathways for acquired resistance to
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in
      NSCLC. We investigated the efficacy of combined trametinib plus taselisib therapy
      using experimentally established EGFR-TKI-resistant NSCLC cell lines. The results
      showed that the feedback loop between MEK/ERK and PI3K/AKT pathways had developed
      in several resistant cell lines, which caused the resistance to single-agent
      treatment with either inhibitor alone. Meanwhile, the combined therapy
      successfully regulated the compensatory activation of the key intracellular
      signals and synergistically inhibited the cell growth of those cells in vitro and
      in vivo. The resistance mechanisms for which the dual kinase inhibitor therapy
      proved effective included (MET) mesenchymal-epithelial transition factor
      amplification, induction of epithelial-to-mesenchymal transition (EMT) and EGFR
      T790M mutation. In further analysis, the combination therapy induced the
      phosphorylation of p38 MAPK signaling, leading to the activation of apoptosis
      cascade. Additionally, long-term treatment with the combination therapy induced
      the conversion from EMT to mesenchymal-to-epithelial transition in the resistant
      cell line harboring EMT features, restoring the sensitivity to EGFR-TKI. In
      conclusion, our results indicate that the combined therapy using MEK and PI3K
      inhibitors is a potent therapeutic strategy for NSCLC with the acquired
      resistance to EGFR-TKIs.

PMID- 30098070
TI  - The regulatory role of curcumin on platelet functions.
AB  - Curcumin, the main ingredient of Curcuma longa L., has been used as a spice and
      as a herbal medicine with different therapeutic characteristics for centuries in
      Asian countries. This phytochemical has been shown to possess beneficial
      antiplatelet activity that has introduced it as a promising candidate for the
      treatment of thromboembolism, atherothrombosis, and inflammatory diseases.
      Platelet dysfunction under different circumstances may lead to cardiovascular
      disease, and curcumin has been shown to have beneficial effects on platelet
      dysfunction in several studies. Therefore, this narrative review is aimed to
      summarize available evidence on the antiplatelet activity of curcumin and related
      molecular mechanisms for this activity.

PMID- 30098069
TI  - Diagnosis of invasive fungal diseases in haematology and oncology: 2018 update of
      the recommendations of the infectious diseases working party of the German
      society for hematology and medical oncology (AGIHO).
AB  - Invasive fungal diseases (IFD) are a primary cause of morbidity and mortality in
      patients with haematological malignancies. These infections are mostly life
      threatening and an early diagnosis and initiation of appropriate antifungal
      therapy are essential for the clinical outcome. Most commonly, Aspergillus and
      Candida species are involved. However, other Non-Aspergillus moulds are
      increasingly identified in case of documented IFD. For definite diagnosis of IFD,
      a combination of diagnostic tools have to be applied, including conventional
      mycological culture and non-conventional microbiological tests such as
      antibody/antigen and molecular tests, as well as histopathology and radiology.
      Although varying widely in cancer patients, the risk of invasive fungal infection
      is highest in those with allogeneic stem cell transplantation and those with
      acute leukaemia and markedly lower in patients with solid cancer. Since the last
      edition of Diagnosis of Invasive Fungal Diseases recommendations of the German
      Society for Hematology and Oncology in 2012, integrated care pathways have been
      proposed for the management and therapy of IFDs with either a diagnostic driven
      strategy as opposed to a clinical or empirical driven strategy. This update
      discusses the impact of this additional evidence and effective revisions.

PMID- 30098071
TI  - Once-daily, prolonged-release tacrolimus vs twice-daily, immediate-release
      tacrolimus in de novo living-donor liver transplantation: A Phase 4, randomized,
      open-label, comparative, single-center study.
AB  - Randomized, open-label, comparative, single-center, Phase 4, 24-week study
      comparing pharmacokinetics (PK), safety, and efficacy of once-daily, prolonged
      release tacrolimus (PR-T) with twice-daily, immediate-release tacrolimus (IR-T)
      in adult de novo living-donor liver transplant (LDLT) recipients in Korea. All
      patients received intravenous tacrolimus from Day 0 (transplantation) for 4 days
      and were randomized (1:1) to receive oral PR-T or IR-T from Day 5. PK profiles
      were taken on Days 6 and 21. Primary endpoint: area under the concentration-time
      curve over 24 hour (AUC0-24 ). Predefined similarity interval for confidence
      intervals of ratios: 80%-125%. Secondary endpoints included: tacrolimus
      concentration at 24 hour (C24 ), patient/graft survival, biopsy-confirmed acute
      rejection (BCAR), treatment-emergent adverse events (TEAEs). One-hundred patients
      were included (PR-T, n = 50; IR-T, n = 50). Compared with IR-T, 40% and 66%
      higher mean PR-T daily doses resulted in similar AUC0-24 between formulations on
      Day 6 (PR-T:IR-T ratio of means 96.8%), and numerically higher AUC0-24 with PR-T
      on Day 21 (128.8%), respectively. Linear relationship was similar between AUC0-24
      and C24 , and formulations. No graft loss/deaths, incidence of BCAR and TEAEs
      similar between formulations. Higher PR-T vs IR-T doses were required to achieve
      comparable systemic exposure in Korean de novo LDLT recipients. PR-T was
      efficacious; no new safety signals were detected.

PMID- 30098072
TI  - Flavin oxidation in flavin-dependent N-monooxygenases.
AB  - Siderophore A (SidA) from Aspergillus fumigatus is a flavin-containing
      monooxygenase that hydroxylates ornithine (Orn) at the amino group of the side
      chain. Lysine (Lys) also binds to the active site of SidA; however, hydroxylation
      is not efficient and H2 O2 is the main product. The effect of pH on steady-state
      kinetic parameters was measured and the results were consistent with Orn binding
      with the side chain amino group in the neutral form. From the pH dependence on
      flavin oxidation in the absence of Orn, a pKa value >9 was determined and
      assigned to the FAD-N5 atom. In the presence of Orn, the pH dependence displayed
      a pKa value of 6.7 +/-0.1 and of 7.70 +/-0.10 in the presence of Lys. Q102
      interacts with NADPH and, upon mutation to alanine, leads to destabilization of
      the C4a-hydroperoxyflavin (FADOOH ). Flavin oxidation with Q102A showed a pKa
      value of ~8.0. The data are consistent with the pKa of the FAD N5-atom being
      modulated to a value >9 in the absence of Orn, which aids in the stabilization of
      FADOOH . Changes in the FAD-N5 environment lead to a decrease in the pKa value,
      which facilitates elimination of H2 O2 or H2 O. These findings are supported by
      solvent kinetic isotope effect experiments, which show that proton transfer from
      the FAD N5-atom is rate limiting in the absence of a substrate, however, is
      significantly less rate limiting in the presence of Orn and or Lys.

PMID- 30098074
TI  - Risk of diabetes with fibrates and statins: a pharmacoepidemiological study in
      VigiBase(r).
AB  - In contrast to statins, the risk of diabetes with fibrates was not clearly
      studied. This study investigates a putative signal of diabetes associated with
      the use of fibrates using the World Health Organization (WHO) global individual
      case safety reports database, VigiBase(r) . We included all reports registered
      until the 31st December 2017 in VigiBase(r) to measure the risk of reporting
      'hyperglycemia or new onset of diabetes' (SMQ term) compared with all other
      reports [as a reporting odds ratio (ROR 95% CI)] for fibrates, statins, and the
      combination fibrates + statins. The likelihood that diabetes resulted from statin
      fibrate interaction was also estimated. According to the interaction additive
      model, a ROR value for coexposure exceeding the sum of the RORs estimated for
      each individual class of drug supports a potential drug-drug interaction (DDI).
      To assess the stability of our results, we performed several sensitivity
      analyses, according to outcome definition and after exclusion of putative
      competitive (hyperglycemic) drugs. We included 19 149 patients exposed to
      fibrates (without statins), 177 323 to statins (without fibrates) and 3 247 to
      statins plus fibrates. In contrast to statins (ROR = 1.75, 95% CI 1.72-1.78), no
      association was found for fibrates (ROR = 0.76, 95% CI 0.71-0.82). The ROR value
      was lower for the combination statins plus fibrates (ROR = 1.46, 95% CI 1.28
      1.67). Similar trends were found in sensitivity analyses. This study, performed
      in the real conditions of use, failed to find a signal of diabetes with fibrates.
      It strengths the association previously described with statin without any
      evidence for a statin-fibrate DDI.

PMID- 30098073
TI  - Using 1 HN amide temperature coefficients to define intrinsically disordered
      regions: An alternative NMR method.
AB  - This report describes a cost-effective experimental method for determining an
      intrinsically disordered protein (IDP) region in a given protein sample. In this
      area, the most popular (and conventional) means is using the amide (1 HN ) NMR
      signal chemical shift distributed in the range of 7.5-8.5 ppm. For this study, we
      applied an additional step: analysis of 1 HN chemical shift temperature
      coefficients (1 HN -CSTCs) of the signals. We measured 1 H-15 N two-dimensional
      NMR spectra of model IDP samples and ordered samples at four temperatures (288,
      293, 298, and 303 K). We derived the 1 HN -CSTC threshold deviation, which gives
      the best correlation of ordered and disordered regions among the proteins
      examined (below -3.6 ppb/K). By combining these criteria with the newly optimized
      chemical shift range (7.8-8.5 ppm), the ratios of both true positive and true
      negative were improved by approximately 19% (62-81%) compared with the
      conventional "chemical shift-only" method.

PMID- 30098075
TI  - Reproductive life planning in women after kidney or liver transplantation.
AB  - INTRODUCTION: To estimate reproductive life planning in post-transplant women and
      to identify factors affecting their pregnancy intentions. MATERIAL AND METHODS: A
      survey study on reproductive life planning was conducted in 217 women of
      childbearing age who underwent kidney or liver transplantation. The results were
      compared with data obtained from 816 healthy women surveyed by the Polish Centre
      for Public Opinion Research. Data were summarized using descriptive statistics.
      RESULTS: Post-transplant women express a similar desire to have a child as women
      in the general population (42% vs 40%, respectively; P = 0.638). A comparable
      majority of childless women would like to give birth (65% vs 77%, P = 0.350).
      More post-transplant women who have one child give up on future procreation plans
      (80% vs 46%, P < 0.001). The main factors affecting post-transplant reproductive
      life planning were age (OR:0.79; 95% CI: 0.73-0.85), number of live births
      (OR:0.22; 95% CI: 0.11-0.43), and use of drugs contraindicated in pregnancy
      (OR:0.27; 95% CI: 0.11-0.63). CONCLUSIONS: Women after kidney or liver
      transplantation, especially childless, have a similar willingness to become
      mothers as those in the general population. For post-transplant women who have
      already given birth, it is worth considering contraceptive counseling because
      these women more often choose to not attempt another pregnancy.

PMID- 30098076
TI  - The protective effect of melatonin on brain ischemia and reperfusion in rats and
      humans: In vivo assessment and a randomized controlled trial.
AB  - Carotid endarterectomy (CEA) is the treatment of choice for carotid stenosis.
      Some patients develop ischemia and reperfusion (I/R) injury after CEA. This study
      was designed to investigate the neuroprotective effects of melatonin on I/R
      injury in both rats and humans. To this end, 36 male rats were evaluated, and a
      double-blind randomized controlled trial (RCT) including 60 patients was
      performed. A rat model of middle cerebral artery occlusion was used to mimic
      cerebral I/R. After 2 hour of occlusion and 24 hour of reperfusion, blood samples
      and brain tissues were harvested for further assessments. Compared with the
      vehicle treatment, melatonin decreased the expression of nuclear factor kappa
      light-chain-enhancer of activated B cells (NF-kappaB) and S100 calcium-binding
      protein beta (S100beta) (P < 0.05) and markedly increased the expression of
      nuclear erythroid 2-related factor 2 (Nrf2), superoxide dismutase (SOD), catalase
      (CAT), and glutathione peroxidase (GPx) (P < 0.05). The participants in the RCT
      took 6 mg/d melatonin orally from 3 days before surgery to 3 days after surgery.
      Blood samples were drawn at the following times: baseline; pre-anesthesia;
      carotid reconstruction completion; and 6, 24, and 72 hour after CEA. Compared
      with the oral placebo treatment, melatonin decreased the expression of NF-kappaB,
      tumor necrosis factor-alpha, interleukin-6 (IL-6), and S100beta (P < 0.05) and
      increased the expression of Nrf2, SOD, CAT, and GPx (P < 0.05) in patients after
      CEA. Our findings suggested that melatonin could ameliorate brain I/R injury
      after CEA and that this outcome was essentially due to the antioxidant and anti
      inflammatory effects of melatonin.

PMID- 30098077
TI  - Hormetic approaches to the treatment of Parkinson's disease: Perspectives and
      possibilities.
AB  - Age-related changes in the brain reflect a dynamic interaction of genetic,
      epigenetic, phenotypic, and environmental factors that can be temporally
      restricted or more longitudinally present throughout the lifespan. Fundamental to
      these mechanisms is the capacity for physiological adaptation through modulation
      of diverse molecular and biochemical signaling occurring from the intracellular
      to the network-systemic level throughout the brain. A number of agents that
      affect the onset and progression of Parkinson's disease (PD)-like effects in
      experimental models exhibit temporal features, and mechanisms of hormetic dose
      responses. These findings have particular significance since the hormetic dose
      response describes the amplitude and range of potential therapeutic effects,
      thereby affecting the design and conduct of studies of interventions against PD
      (and other neurodegenerative diseases), and may also be important to a broader
      consideration of hormetic processes in resilient adaptive responses that might
      afford protection against the onset and/or progression of PD and related
      disorders.

PMID- 30098079
TI  - Chemotherapy-induced alopecia - the urgent need for treatment options.

PMID- 30098078
TI  - Metallothionein-I/II expression associates with the astrocyte DNA damage response
      and not Alzheimer-type pathology in the aging brain.
AB  - Oxidative stress and oxidative DNA damage are early features of mild cognitive
      impairment and Alzheimer's disease (AD), occurring before the formation of
      classical AD neuropathology, and resulting from an imbalance between pro- and
      anti-oxidants. Astrocytes play a major neuroprotective role, producing high
      levels of anti-oxidants including metallothionein-I and -II (MT-I/II). In the
      present study we characterized the immunoreactive profile of MT-I/II in the
      temporal cortex of the Cognitive Function and Ageing Study (CFAS) aging
      population-representative neuropathology cohort, and examined H2 O2 -modulation
      of MT transcription by human astrocytes. MT-I/II is primarily expressed by
      astrocytes in the aging brain, but is also associated with pyramidal neurons in a
      small proportion of cases. Astrocyte expression of MT-I/II does not correlate
      with Alzheimer-type pathology (Abeta plaques and neurofibrillary tangles) but
      does relate to astrocyte oxidative DNA damage (rs  = .312, p = .006) and the
      astrocyte response to oxidative DNA damage in vivo (rs  = .238, p = .04), and MT
      gene expression is significantly induced in human astrocytes response to
      oxidative stress in vitro (p = .01). In contrast, neuronal MT-I/II does not
      relate to oxidative DNA damage or the neuronal DNA damage response, but is
      significantly higher in cases with high levels of local tangle pathology (p =
      .007). As MT-I/II is neuroprotective against oxidative stress, modulation of MT
      I/II expression is a potential therapeutic target to treat the onset and
      progression of cognitive impairment.

PMID- 30098080
TI  - Variability in response to salinity stress in natural Tunisian populations of
      Hordeum marinum subsp. marinum.
AB  - Soil salinity is one of the most serious environmental factors affecting crop
      productivity around the world. In this study, we analysed morpho-physiological
      variation in responses to salt stress in Tunisian populations of Hordeum marinum
      subsp. marinum. The plants were grown under two treatments (0 and 200 mm NaCl)
      until maturity. A total of 19 quantitative traits were measured before and during
      the harvest. It was observed that most studied traits are influenced by the
      increasing salinity. High to moderate broad-sense heritability (H2 ) were noted
      for most of parameters under control and salt treatment, implying that salt
      tolerance is moderately heritable and environmental variation plays an equally
      important role. The majority of correlations between measured traits under the
      two treatments are positive, where the strongest correlations were between spike
      number (SN) and weight (SW). Based on the salt response index (SRI) values, SN
      and SW are the most affected by salinity. The 150 studied lines formed three
      groups according to the SRI values of the 19 quantitative parameters, of which
      101 were moderately sensitive, 27 tolerant and 22 highly tolerant. Overall
      genetic variation of H. marinum in response to salt stress may provide novel
      insight to identify genes responsible for salt tolerance.

PMID- 30098082
TI  - Self-perceived preparedness of final year dental students in a developing country
      A multi-institution study.
AB  - AIMS: To evaluate the self-perceived preparedness to practice of final year
      dental undergraduate students in three dental institutions. METHODS: Dental
      undergraduate students in their final year from three dental institutions in
      Pakistan were invited to participate in an online study to assess self-perceived
      preparedness using a validated preparedness assessment scale. RESULTS: In total,
      134 students responded to the questionnaire yielding a response rate of 72%.
      Students felt adequately prepared to carry out several clinical procedures
      including clinical assessment, fillings, tooth extractions and communication
      skills. However, perceived preparedness was low in the students' ability to
      undertake intraoral radiographs, treatment planning, crowns, multirooted
      endodontics, research skills, referral for suspected oral cancer and raising
      concerns regarding inappropriate behaviour of colleagues. CONCLUSIONS: This is
      the first study which investigates the self-perceived preparedness of final year
      undergraduate dental students in Pakistan. The results show that the self
      perceived preparedness of final year students was satisfactory for a range of
      clinical and affective skills. However, several areas of weaknesses were
      identified which underscore the need for additional training and consolidation.

PMID- 30098081
TI  - Stillbirth and preterm birth and associated factors in one of the largest cities
      in central Vietnam.
AB  - AIM: Little is known about the rate of stillbirths, preterm births and associated
      risk factors in resource-limited settings like Vietnam. This study reports those
      rates for Da Nang, which is one of the largest cities in central Vietnam.
      METHODS: Data on 20 762 births including stillbirths and preterm births and
      associated risk factors were prospectively collected from health facilities from
      April 2015 to March 2016. RESULTS: The data represented 85% of the total births
      in Da Nang during the study period, and a stillbirth rate of 9.7 per 1000 live
      births was recorded. The preterm rate for live births was just under 5%.
      Independent factors associated with an increased risk of stillbirth and preterm
      births were mothers aged 35 plus, working as farmers, living in the provinces and
      a history of abortion. Mothers under 20 years with previous preterm births faced
      a higher risk of another preterm birth. CONCLUSION: The stillbirth and premature
      birth rates in Da Nang were higher than rates in high-income countries.
      Developing registration programmes in Vietnam will provide improved data that
      will enable researchers and policymakers to identify strategies to reduce the
      number of stillbirths and premature births.

PMID- 30098084
TI  - Fluorescence Probes for ALKBH2 Allow the Measurement of DNA Alkylation Repair and
      Drug Resistance Responses.
AB  - The DNA repair enzyme ALKBH2 is implicated in both tumorigenesis as well as
      resistance to chemotherapy in certain cancers. It is currently under study as a
      potential diagnostic marker and has been proposed as a therapeutic target. To
      date, however, there exist no direct methods for measuring the repair activity of
      ALKBH2 in vitro or in biological samples. Herein, we report a highly specific,
      fluorogenic probe design based on an oligonucleotide scaffold that reports
      directly on ALKBH2 activity both in vitro and in cell lysates. Importantly, the
      probe enables the monitoring of cellular regulation of ALKBH2 activity in
      response to treatment with the chemotherapy drug temozolomide through a simple
      fluorescence assay, which has only previously been observed through indirect
      means such as qPCR and western blots. Furthermore, the probe provides a viable
      high-throughput assay for drug discovery.

PMID- 30098083
TI  - Tuning Gold Nanoparticles with Chelating Ligands for Highly Efficient
      Electrocatalytic CO2 Reduction.
AB  - Capped chelating organic molecules are presented as a design principle for tuning
      heterogeneous nanoparticles for electrochemical catalysis. Gold nanoparticles
      (AuNPs) functionalized with a chelating tetradentate porphyrin ligand show a 110
      fold enhancement compared to the oleylamine-coated AuNP in current density for
      electrochemical reduction of CO2 to CO in water at an overpotential of 340 mV
      with Faradaic efficiencies (FEs) of 93 %. These catalysts also show excellent
      stability without deactivation (<5 % productivity loss) within 72 hours of
      electrolysis. DFT calculation results further confirm the chelation effect in
      stabilizing molecule/NP interface and tailoring catalytic activity. This general
      approach is thus anticipated to be complementary to current NP catalyst design
      approaches.

PMID- 30098085
TI  - Iterative l-Tryptophan Methylation in Psilocybe Evolved by Subdomain Duplication.
AB  - Psilocybe mushrooms are best known for their l-tryptophan-derived psychotropic
      alkaloid psilocybin. Dimethylation of norbaeocystin, the precursor of psilocybin,
      by the enzyme PsiM is a critical step during the biosynthesis of psilocybin.
      However, the "magic" mushroom Psilocybe serbica also mono- and dimethylates l
      tryptophan, which is incompatible with the specificity of PsiM. Here, a second
      methyltransferase, TrpM, was identified and functionally characterized. Mono- and
      dimethylation activity on l-tryptophan was reconstituted in vitro, whereas
      tryptamine was rejected as a substrate. Therefore, we describe a second l
      tryptophan-dependent pathway in Psilocybe that is not part of the biosynthesis of
      psilocybin. TrpM is unrelated to PsiM but originates from a retained ancient
      duplication event of a portion of the egtDB gene that encodes an ergothioneine
      biosynthesis enzyme. During mushroom evolution, this duplicated gene was widely
      lost but re-evolved sporadically and independently in various genera. We propose
      a new secondary metabolism evolvability mechanism, in which weakly selected genes
      are retained through preservation in a widely distributed, conserved pathway.

PMID- 30098086
TI  - Tunable Orthogonal Reversible Covalent (TORC) Bonds: Dynamic Chemical Control
      over Molecular Assembly.
AB  - Dynamic assembly of macromolecules in biological systems is one of the
      fundamental processes that facilitates life. Although such assembly most commonly
      uses noncovalent interactions, a set of dynamic reactions involving reversible
      covalent bonding is actively being exploited for the design of functional
      materials, bottom-up assembly, and molecular machines. This Minireview highlights
      recent implementations and advancements in the area of tunable orthogonal
      reversible covalent (TORC) bonds for these purposes, and provides an outlook for
      their expansion, including the development of synthetically encoded
      polynucleotide mimics.

PMID- 30098087
TI  - A Carboxylate to Amide Substitution That Switches Protein Folds.
AB  - Metamorphic proteins are biomolecules prone to adopting alternative
      conformations. Because of this feature, they represent ideal systems to
      investigate the general rules allowing primary structure to dictate protein
      topology. A comparative molecular dynamics study was performed on the denatured
      states of two proteins, sharing nearly identical amino-acid sequences (88 %) but
      different topologies, namely an all-alpha-helical bundle protein named GA 88 and
      an alpha+beta-protein named GB 88. The analysis allowed successful design of and
      experimental validation of a site-directed mutant that promotes, at least in
      part, the switch in folding from GB 88 to GA 88. The mutated position, in which a
      glutamic acid was replaced by a glutamine, does not make any intramolecular
      interactions in the native state of GA 88, such that its stabilization can be
      explained by considering the effects on the denatured state. The results
      represent a direct demonstration of the role of the denatured state in sculpting
      native structure.

PMID- 30098089
TI  - Supramolecular Assemblies with Near-Infrared Emission Mediated in Two Stages by
      Cucurbituril and Amphiphilic Calixarene for Lysosome-Targeted Cell Imaging.
AB  - A two-stage mediated near-infrared (NIR) emissive supramolecular assembly for
      lysosome-targeted cell imaging is presented. 4,4'-Anthracene-9,10-diylbis(ethene
      2,1-diyl))bis(1-ethylpyridin-1-ium) bromide (ENDT) was synthesized as an organic
      dye with weak fluorescence emission at 625 nm. When ENDT complexes with
      cucurbit[8]uril (CB[8]), this binary supramolecular complex assembles into
      nanorods with a near-infrared fluorescence emission (655 nm) and fluorescence
      enhancement as the first stage. Such supramolecular complexes interact with lower
      rim dodecyl-modified sulfonatocalix[4]arene (SC4AD) to form nanoparticles for
      further fluorescence enhancement as the second stage. Furthermore, based on a co
      staining experiment with LysoTracker Blue, such nanoparticles can be applied in
      NIR lysosome-targeted cell imaging.

PMID- 30098088
TI  - Physiological, biochemical and molecular responses to water stress and
      rehydration in Mediterranean adapted tomato landraces.
AB  - Mediterranean tomato landraces adapted to arid environments represent an option
      to counteract drought, and to address the complexity of responses to water
      deficit and recovery, which is a crucial component of plant adaptation
      mechanisms. We investigated physiological, biochemical and molecular responses of
      two Mediterranean tomato landraces, 'Locale di Salina' (Lc) and 'Pizzutello di
      Sciacca' (Pz) under two dehydration periods and intermediate rehydration in
      greenhouse pot experiments. Relationship between CO2 assimilation (A) and
      stomatal conductance under severe water stress (gs  < 0.05 mol.m-2 .s-1 )
      indicated the occurrence of stomatal and non-stomatal limitations of
      photosynthesis. Gas exchange promptly recovered within 2-3 days of rehydration.
      ABA and gs showed a strict exponential relationship. Both leaf ABA and proline
      peaked under severe water stress. Lc showed higher accumulation of ABA and higher
      induction of the expression of both NCED and P5CS genes than Pz. Poly(ADP-ribose)
      polymerase increased during imposition of stress, mainly in Lc, and decreased
      under severe water stress. The two landraces hardly differed in their
      physiological performance. Under severe water stress, gs showed low sensitivity
      to ABA, which instead controlled stomatal closure under moderate water stress (gs
      > 0.15 mol.m-2 .s-1 ). The prompt recovery after rehydration of both landraces
      confirmed their drought-tolerant behaviour. Differences between the two landraces
      were instead observed at biochemical and molecular levels.

PMID- 30098091
TI  - Deep sequencing identified potential miRNAs involved in defence response, stress
      and plant growth characteristics of wild genotypes of cardamom.
AB  - Cardamom has long been used as a food flavouring agent and in ayurvedic medicines
      for mouth ulcers, digestive problems and even depression. Extensive occurrence of
      pests and diseases adversely affect its cultivation and result in substantial
      reductions in total production and productivity. Numerous studies revealed the
      significant role of miRNAs in plant biotic stress responses. In the current
      study, miRNA profiling of cultivar and wild cardamom genotypes was performed
      using an Ion Proton sequencer. We identified 161 potential miRNAs representing 42
      families, including monocot/tissue-specific and 14 novel miRNAs in both
      genotypes. Significant differences in miRNA family abundance between the
      libraries were observed in read frequencies. A total of 19 miRNAs (from known
      miRNAs) displayed a twofold difference in expression between wild and cultivar
      genotypes. We found 1168 unique potential targets for 40 known miRNA families in
      wild and 1025 potential targets for 42 known miRNA families in cultivar
      genotypes. The differential expression analysis revealed that most miRNAs
      identified were highly expressed in cultivars and, furthermore, lower expression
      of miR169 and higher expression of miR529 in wild cardamom proved evidence that
      wild genotypes have stronger drought stress tolerance and floral development than
      cultivars. Potential targets predicted for the newly identified miRNAs from the
      miRNA libraries of wild and cultivar cardamom genotypes involved in metabolic and
      developmental processes and in response to various stimuli. qRT-PCR confirmed
      miRNAs were differentially expressed between wild and cultivar genotypes.
      Furthermore, four target genes were validated experimentally to confirm miRNA
      mRNA target pairing using RNA ligase-mediated 5' Rapid Amplification of cDNA Ends
      (5'RLM-RACE) PCR.

PMID- 30098090
TI  - Ammonia Storage by Reversible Host-Guest Site Exchange in a Robust Metal-Organic
      Framework.
AB  - MFM-300(Al) shows reversible uptake of NH3 (15.7 mmol g-1 at 273 K and 1.0 bar)
      over 50 cycles with an exceptional packing density of 0.62 g cm-3 at 293 K. In
      situ neutron powder diffraction and synchrotron FTIR micro-spectroscopy on ND3
      @MFM-300(Al) confirms reversible H/D site exchange between the adsorbent and
      adsorbate, representing a new type of adsorption interaction.

PMID- 30098092
TI  - Measurement of telomere length in cells from pleural effusion: Asbestos exposure
      causes telomere shortening in pleural mesothelial cells.
AB  - We estimated the telomere lengths of neoplastic and non-neoplastic mesothelial
      cells and examined their correlation with asbestos exposure and the expression of
      markers of mesothelial malignancy. Cell blocks of pleural effusion obtained from
      35 cases of non-neoplastic disease (NN), 12 cases of malignant mesothelioma (MM)
      and 12 cases of carcinomatous effusion due to lung adenocarcinoma (LA) were
      examined. Fifteen of the 35 NN cases had pleural plaques (NNpp+) suggestive of
      asbestos exposure, and the other 20 cases had no pleural plaques (NNpp-).
      Telomere length was measured using the tissue quantitative fluorescence in situ
      hybridization method, and expressed as normalized telomere-to-centromere ratio.
      NN cases had significantly longer telomeres than MM (P < 0.001) and LA (P <
      0.001) cases. Telomeres in NNpp+ cases were slightly shorter than those of NNpp-
      cases (P = 0.047). MM and LA showed almost the same telomere length. NN cases
      with shorter telomeres tended to show aberrant expression of epithelial membrane
      antigen (EMA), CD146, glucose transporter 1 (GLUT1) and IGF-II messenger RNA
      binding protein 3 (IMP3). These results suggest that telomere shortening and
      subsequent genetic instability play an important role in the development of MM.
      Measurement of telomere length of cells in pleural effusion might be helpful for
      earlier detection of MM.

PMID- 30098093
TI  - An observational, multicentre study of cabazitaxel in patients with metastatic
      castration-resistant prostate cancer previously treated with docetaxel
      (CAPRISTANA).
AB  - OBJECTIVES: To obtain routine clinical practice data on cabazitaxel usage
      patterns for patients with metastatic castration-resistant prostate cancer
      (mCRPC) and to describe physician-assessed cabazitaxel effectiveness, health
      related quality of life (HRQoL) and safety. PATIENTS AND METHODS: CAPRISTANA was
      an international, observational cohort study examining cabazitaxel use for the
      treatment of patients with mCRPC. Effectiveness was assessed by overall survival
      (OS), progression-free survival (PFS), time to treatment failure (TTF) and
      disease control rate. HRQoL was assessed using the Functional Assessment of
      Cancer Therapy-Prostate questionnaire (FACT-P) and the three-level European
      Quality of Life questionnaire (EQ-5D-3L). Safety was assessed by adverse event
      (AE) reporting. RESULTS: A total of 189 patients were treated across 54 centres
      between April 2012 and June 2016. At baseline, 58.7% had >=1 comorbidity, 93.7%
      had an Eastern Cooperative Oncology Group performance status <=1, and 60.1% had a
      Gleason score at diagnosis of >=8. Patients received a median of 6 cabazitaxel
      cycles; 84.7% received cabazitaxel as second-line therapy. The median OS, PFS and
      TTF were 13.2, 5.6 and 4.4 months, respectively. Cabazitaxel led to disease
      control in 52.9% of patients. HRQoL was maintained (40.3%) or improved (32.2%) in
      72.5% of patients based on total FACT-P scores. Interestingly, 53.6% of patients
      reported pain improvement and a further 21.2% maintained pain control based on
      FACT-P prostate cancer-specific pain scores. The most common treatment-related
      grade >=3 AEs were neutropenia (7.9%) and anaemia (2.1%). CONCLUSION: Patients in
      CAPRISTANA treated with cabazitaxel had similar disease outcomes and safety
      profiles compared with large phase III clinical trials. Most patients had
      maintained or improved HRQoL scores; >70% of patients had maintained or improved
      pain control.

PMID- 30098095
TI  - Stereospecific beta-l-Rhamnopyranosylation through an SN i-Type Mechanism by
      Using Organoboron Reagents.
AB  - Stereospecific beta-l-rhamnopyranosylations were conducted using a 1,2-anhydro-l
      rhamnopyranose donor and mono-ol or diol acceptors in the presence of a glycosyl
      acceptor-derived borinic or boronic ester. Reactions proceeded smoothly to
      provide the corresponding beta-l-rhamnopyranosides (beta-l-Rhap) with complete
      stereoselectivity in moderate to high yields without any further additives under
      mild conditions. Mechanistic studies of the borinic ester mediated glycosylation
      using 13 C kinetic isotope effect (KIE) measurements and DFT calculations were
      consistent with a concerted SN i mechanism with an exploded transition state. In
      addition, the present glycosylation method was applied successfully to the
      synthesis of a trisaccharide, alpha-l-Rhap-(1,2)-beta-l-Rhap-(1,4)-Glcp, derived
      from Streptococcus pneumoniae serotypes 7B, 7C, and 7D.

PMID- 30098094
TI  - Prevalence and phenotype of the c.1529C>T SPG7 variant in adult-onset cerebellar
      ataxia in Italy.
AB  - BACKGROUND AND PURPOSE: Hereditary ataxias are heterogeneous groups of
      neurodegenerative disorders, characterized by cerebellar syndromes associated
      with dysarthria, oculomotor and corticospinal signs, neuropathy and cognitive
      impairment. Recent reports have suggested mutations in the SPG7 gene, causing the
      most common form of autosomal recessive spastic paraplegia (MIM#607259), as a
      main cause of ataxias. The majority of described patients were homozygotes or
      compound heterozygotes for the c.1529C>T (p.Ala510Val) change. We screened a
      cohort of 895 Italian patients with ataxia for p.Ala510Val in order to define the
      prevalence and genotype-phenotype correlation of this variant. METHODS: We set up
      a rapid assay for c.1529C>T using restriction enzyme analysis after polymerase
      chain reaction amplification. We confirmed the diagnosis with Sanger sequencing.
      RESULTS: We identified eight homozygotes and 13 compound heterozygotes, including
      two novel variants affecting splicing. Mutated patients showed a pure cerebellar
      ataxia at onset, evolving in mild spastic ataxia (alternatively) associated with
      dysarthria (~80% of patients), urinary urgency (~30%) and pyramidal signs (~70%).
      Comparing homozygotes and compound heterozygotes, we noted a difference in age at
      onset and Scale for the Assessment and Rating of Ataxia score between the two
      groups, supporting an earlier and more severe phenotype in compound heterozygotes
      versus homozygotes. CONCLUSIONS: The SPG7 c.1529C>T (p.Ala510Val) mutants
      accounted for 2.3% of cerebellar ataxia cases in Italy, suggesting that this
      variant should be considered as a priority test in the presence of late-onset
      pure ataxia. Moreover, the heterozygous/homozygous genotype appeared to predict
      the onset of clinical manifestation and disease progression.

PMID- 30098096
TI  - Social wasps, crickets and cockroaches contribute to pollination of the
      holoparasitic plant Mitrastemon yamamotoi (Mitrastemonaceae) in southern Japan.
AB  - Mitrastemon yamamotoi is completely embedded within the tissues of its hosts,
      except during the reproductive stage, when aboveground parts emerge from host
      tissues. Its highly modified appearance has attracted attention of many
      botanists, but very little is known about the reproductive system. Floral
      visitors to M. yamamotoi were observed in southern Japan. Pollination experiments
      were conducted to determine the plant's self-compatibility and pollen limitation,
      as well as the contribution of diurnal and nocturnal visitors to fruit set and
      outcrossing. Mitrastemon yamamotoi is mainly pollinated by social wasps, but
      previously unnoticed pollinators (i.e. crickets and cockroaches) are also
      important, based on visitation frequency and pollen loads. Results of the
      pollination experiments suggest that nocturnal visitors, such as crickets and
      cockroaches, contribute to geitonogamous pollination, whereas diurnal visitors,
      such as social wasps, facilitate outcrossing. The unexpected pollinator
      assemblage of M. yamamotoi might be influenced by multiple factors, including the
      highly modified flowers that are produced close to the ground in dark understorey
      environments, the species' winter-flowering habit and the location of the study
      site (i.e. near the northern limit of the species' range). Considering that M.
      yamamotoi occurs widely in subtropical and tropical forests in Asia, additional
      studies are needed to assess pollinator assemblages of M. yamamotoi at other
      locations.

PMID- 30098097
TI  - Photo-Organocatalytic Enantioselective Radical Cascade Reactions of Unactivated
      Olefins.
AB  - Radical cascade processes are invaluable for their ability to rapidly construct
      complex chiral molecules from simple substrates. However, implementing catalytic
      asymmetric variants is difficult. Reported herein is a visible-light-mediated
      organocatalytic strategy that exploits the excited-state reactivity of chiral
      iminium ions to trigger radical cascade reactions with high enantioselectivity.
      By combining two sequential radical-based bond-forming events, the method
      converts unactivated olefins and alpha,beta-unsaturated aldehydes into chiral
      adducts in a single step. The implementation of an asymmetric three-component
      radical cascade further demonstrates the complexity-generating power of this
      photochemical strategy.

PMID- 30098098
TI  - Dentists' responses about the effectiveness of continuing education activities.
AB  - OBJECTIVE: To report the responses of dentists about the effectiveness of
      continuing education (CE) activities. METHODS: This cross-sectional study
      involved the administration of a pilot-tested questionnaire amongst dentists from
      different cities of the eastern province of Saudi Arabia. A calculated sample of
      dentists (n = 323) was approached in person to collect their responses about CE
      activities they attended during the last one year. Descriptive statistics and
      multivariate logistic regression analyses were performed. RESULTS: The response
      rate was 79.5% as 257 dentists returned completed questionnaires. There were
      54.9% male and 45.1% female participants (mean age 31.18 +/- 12.4 years). The
      majority of participants reported an improvement in knowledge (79.8%), a
      motivation for learning (79.8%), and quality of dental care (73.9%) as a result
      of CE activities. More than two-thirds recognised the importance of CE courses
      for maintaining licensure in dentistry, and 91.1% felt the need to increase CE
      activities. Logistic regression models showed that male participants were less
      likely (OR = 0.48, P = 0.05) than female counterparts to report an improvement in
      clinical skills. Having a private job (OR = 2.38 P = 0.005) and >10 years since
      graduation (OR = 1.84, P = 0.05) were associated with an improvement in clinical
      skills. Believing in the importance of CE activities for maintaining licensure
      was significantly associated with the effectiveness of CE activities in improving
      knowledge (OR = 2.76, P = 0.01), clinical skills (OR = 2.02, P = 0.04) and
      patient satisfaction (OR = 2.22, P = 0.01). CONCLUSION: The majority of dentists
      recognised that CE activities were effective in improving their knowledge,
      clinical practice, quality of patient care and motivation for learning.

PMID- 30098099
TI  - Food Choice Experiments Indicate Selective Fungivorous Predation in Fisculla
      terrestris (Thecofilosea, Cercozoa).
AB  - Thecofilosea is a class in Cercozoa comprising mainly freshwater inhabiting
      algivores. Since direct observation of amoeboid protists in soil is not possible,
      the prey spectra of their terrestrial relatives remain obscure. To test for
      grazing selectivity and the preferred prey of terrestrial thecofiloseans, we
      conducted a food choice experiment including yeasts and algae as prey. When being
      offered all food sources at once, the yeast cells were strongly reduced, whereas
      the abundance of the algae only slightly decreased. Since Fisculla terrestris
      thrives with fungal prey, it must be considered as a predator of eukaryotes with
      high preference for fungal cells.

PMID- 30098100
TI  - The ArabidopsisTHADA homologue modulates TOR activity and cold acclimation:
      Genetic modulation of cold acclimation in Arabidposis.
AB  - Low temperature is one of the most important environmental factors that affect
      global survival of humans and animals and equally importantly the distribution of
      plants and crop productivity. Survival of metazoan cells under cold stress
      requires regulation of the sensor-kinase Target Of Rapamycin (TOR). TOR controls
      growth of eukaryotic cells by adjusting anabolic and catabolic metabolism.
      Previous studies identified the Thyroid Adenoma Associated (THADA) gene as the
      major effect locus by positive selection in the evolution of modern human adapted
      to cold. Here we investigate the role of THADA in TOR signaling and cold
      acclimation of plants. We applied BLAST searches and homology modeling to
      identify the AtTHADA (AT3G55160) in Arabidopsis thaliana as the highly probable
      orthologue protein. Reverse genetics approaches were combined with immunological
      detection of TOR activity and metabolite profiling to address the role of the TOR
      and THADA for growth regulation and cold acclimation. Depletion of the AtTHADA
      gene caused complete or partial loss of full-length mRNA, respectively, and
      significant retardation of growth under non-stressed conditions. Furthermore,
      depletion of AtTHADA caused hypersensitivity towards low-temperatures. Atthada
      displayed a lowered energy charge. This went along with decreased TOR activity,
      which offers a molecular explanation for the slow growth phenotype of Atthada.
      Finally, we used TOR RNAi lines to identify the de-regulation of TOR activity as
      one determinant for sensitivity towards low-temperatures. Taken together our
      results provide evidence for a conserved function of THADA in cold acclimation of
      eukaryotes and suggest that cold acclimation in plants requires regulation of
      TOR.

PMID- 30098101
TI  - GhSTOP1, a C2H2 type zinc finger transcription factor is essential for Aluminum
      and proton stress tolerance and lateral root initiation in cotton.
AB  - The Aluminum (Al) and proton (H+ ) ions are major acid soil stress factors
      deleteriously affecting plant root growth and crop yield. In our preliminary
      studies, cotton seedlings (Gossypium hirsutum L.) displayed very sensitive
      phenotypes to Al and H+ rhizotoxicities. Based on previous Arabidopsis results,
      we aimed to characterize the Al stress responsive Sensitive to Proton
      rhizotoxicity 1 (GhSTOP1) transcription system in cotton by RNAi mediated down
      regulation. With the help of seed embryo apex explants, we developed transgenic
      cotton plants overexpressing a GhSTOP1-RNAi cassette with NPTII selection.
      Kanamycin tolerant T1 seedlings were further considered for Al and H+ stress
      tolerance studies. Down-regulation of the GhSTOP1 displayed increased sensitivity
      to Al and proton rhizotoxicities and the root growth was significantly reduced in
      RNAi-lines. The expression profile of GhALMT1 (Aluminum-activated Malate
      Transporter 1), GhMATE (Multidrug and Toxic Compound Extrusion), GhALS3 (Aluminum
      Sensitive 3) and the key genes involved in the GABA shunt were downregulated in
      the transgenic RNAi lines. Additionally, the lateral root initiation process was
      delayed and the expression of GhNAC1 which is involved in lateral root initiation
      was also suppressed in transgenic lines. Besides, overexpression of GhSTOP1 in
      Arabidopsis accelerated root growth and AtMATE and AtALMT1 expression under Al
      stress conditions. These analyses indicate that the GhSTOP1 is necessary for the
      expression of several genes which are necessary for acid soil tolerance
      mechanisms and lateral root initiation. This article is protected by copyright.
      All rights reserved.

PMID- 30098102
TI  - Inflammatory and neuropathic pain conditions do not primarily evoke anxiety-like
      behaviours in C57BL/6 mice.
AB  - BACKGROUND: Chronic pain is often accompanied by comorbidities like anxiety and
      depression. The temporal correlations, as well as the underlying mechanisms of
      these reciprocal correlations, are unclear. Moreover, preclinical studies
      examining emotional behaviour are very controversial, and a chronological
      analysis of anxiety-like behaviour in mouse pain models considering both genders
      has not been performed so far. METHODS: We used several behavioural tests to
      assess and validate anxiety-like behaviour in complete Freund's adjuvant (CFA)
      and spared nerve injury (SNI) pain models in C57BL/6 mice. Among these were the
      elevated plus maze test, open field test, hole-board test and light-dark test.
      Additionally, we included a late stage analysis of depression-like behaviour
      using the forced swim test. All tests were applied once for each cohort of mice.
      Importantly, we used C57BL/6N mice of both genders; we investigated the effect of
      social isolation, the impact of pain induction to either the right or left hind
      limb and also investigated C57BL/6J mice. RESULTS: The validity of test
      conditions was confirmed using the anxiogenic drugs Yohimbine and
      Pentylenetetrazol. Anxiety-like behaviour was analysed throughout the time period
      when mice exhibited hypersensitivity to mechanical stimuli. We did not observe
      any consistent alteration in anxiety-like behaviour at any of the investigated
      time points between 1 and 14 days following CFA-induced inflammation or 3 and 84
      days following SNI surgery using different behavioural tests. CONCLUSIONS:
      Inflammatory and neuropathic pain conditions do not primarily evoke anxiety- and
      depression-like behavioural alterations within the herein investigated time
      period. SIGNIFICANCE: Anxiety-like behaviour is not primarily altered following
      CFA and SNI in C57BL6 mice, irrespective of the gender, mouse sub-strain, housing
      conditions or affected body side within the herein investigated time period.

PMID- 30098103
TI  - Fasting hypoglycemia is associated with disease progression in presymptomatic
      early stage type 1 diabetes.
AB  - OBJECTIVE: In children with presymptomatic type 1 diabetes, intermittent
      hyperglycemia and rising hemoglobin A1c levels are a known signal of progression
      toward insulin-dependency. Episodes of hypoglycemia, however, have also been
      reported in one published case. We investigated the prevalence of hypoglycemia
      and its association with disease progression in children with presymptomatic type
      1 diabetes. METHODS: We compared the frequency of hypoglycemic fasting blood
      glucose levels (<60 mg/dL) in 48 autoantibody negative and 167 multiple beta-cell
      autoantibody positive children aged 2 to 5 years. We classified the autoantibody
      positive children into three categories based on their glucose levels in fasting
      state (hypoglycemic [<60 mg/dL], normoglycemic [60-99 mg/dL] or hyperglycemic
      [>=100 mg/dL]). We then compared the glucose levels under challenge during oral
      glucose tolerance tests (OGTTs) between the three categories. RESULTS: In the
      autoantibody positive children, 5.1% of the fasting samples were hypoglycemic,
      while in the autoantibody negative children no hypoglycemia was observed.
      Hypoglycemia occurred more often in autoantibody positive children who had
      already entered stage 2 or stage 3 of type 1 diabetes than in stage 1 patients (P
      = 0.02). Children who had hypoglycemic compared to normoglycemic fasting blood
      glucose values had higher 120-minute blood glucose values under OGTT challenge,
      and a higher rate of pathological OGTTs (P = 0.04). CONCLUSIONS: Fasting
      hypoglycemia seems to be an indicator of disease progression in presymptomatic
      type 1 diabetes and may therefore represent a novel marker for the identification
      of children who should be monitored more closely for progression toward insulin
      dependent type 1 diabetes.

PMID- 30098105
TI  - Labeling of Phosphatidylinositol Lipid Products in Cells through Metabolic
      Engineering by Using a Clickable myo-Inositol Probe.
AB  - Phosphatidylinositol (PI) lipids control critical biological processes, so
      aberrant biosynthesis often leads to disease. As a result, the capability to
      track the production and localization of these compounds in cells is vital for
      elucidating their complex roles. Herein, we report the design, synthesis, and
      application of clickable myo-inositol probe 1 a for bioorthogonal labeling of PI
      products. To validate this platform, we initially conducted PI synthase assays to
      show that 1 a inhibits PI production in vitro. Fluorescence microscopy
      experiments next showed probe-dependent imaging in T-24 human bladder cancer and
      Candida albicans cells. Growth studies in the latter showed that replacement of
      myo-inositol with probe 1 a led to an enhancement in cell growth. Finally,
      fluorescence-based TLC analysis and mass spectrometry experiments support the
      labeling of PI lipids. This approach provides a promising means for tracking the
      complex biosynthesis and trafficking of these lipids in cells.

PMID- 30098104
TI  - Behavioural and neural responses to aversive visceral stimuli in women with
      primary dysmenorrhoea.
AB  - BACKGROUND: Chronic pelvic pain, in particular dysmenorrhoea, is a significant
      yet unresolved healthcare problem in gynaecology. As interoceptive sensitivity
      and underlying neural mechanisms remain incompletely understood, this functional
      magnetic resonance imaging (fMRI) study assessed behavioural and neural responses
      to visceral stimuli in primary dysmenorrhoea (PMD). METHODS: Women with PMD (N =
      19) without psychological comorbidity and healthy women (N = 20) were compared
      with respect to visceral sensory and pain thresholds, and to neural responses to
      individually calibrated mildly painful and painful rectal distensions implemented
      during scanning. Trial-by-trial ratings of perceived intensity were accomplished
      with visual analogue scales (VAS). RESULTS: Although women with dysmenorrhoea
      reported significantly higher chronic pain intensity and pain interference with
      daily life activities (p < 0.01, assessed with the West Haven-Yale
      Multidimensional Pain Inventory), there were no differences between groups in
      visceral sensitivity and mean trial-by-trial VAS ratings were virtually
      identical. Analysis of neural responses revealed activation in brain regions
      previously shown to be involved in the processing of visceral stimuli with
      differences between painful and mildly painful stimulation, but no group
      differences were found even when using a liberal statistical threshold.
      CONCLUSIONS: Dysmenorrhoea patients show unaltered perceptual and neural
      responses to experimental interoceptive stimuli. Despite limited sample size,
      these negative results argue against a generalized sensitization towards
      interoceptive stimuli in patients without psychological comorbidities. Future
      studies should clarify the role of psychosocial factors in central sensitization
      using more pain region-specific models in larger and clinically more
      heterogeneous samples. SIGNIFICANCE: Despite higher chronic pain and pain
      interference with daily life activities, women with primary dysmenorrhoea do not
      differ from healthy women with respect to visceral sensitivity or neural
      processing of aversive interoceptive stimuli induced by rectal distensions.
      Generalized sensitization may be present only in subgroups with pronounced
      psychosocial or psychiatric disturbances.

PMID- 30098106
TI  - Prevalence of self-reported chronic pain among adolescents: Evidence from 42
      countries and regions.
AB  - BACKGROUND: Reports of the overall chronic pain prevalence and its associated
      demographic characteristics among adolescents vary greatly across existing
      studies. Using internationally comparable data, this study investigates age, sex
      and country-level effects in the prevalence of chronic single-site and multi-site
      pain among adolescents during the last six months preceding the survey. METHODS:
      Data (n = 214,283) from the 2013/2014 Health Behaviour in School-aged Children
      (HBSC) study were used including nationally representative samples of 11-, 13-
      and 15-year-olds from general schools in 42 participating countries. Multilevel
      logistic regression analyses were used. RESULTS: The overall proportion of
      adolescents reporting chronic weekly pain during the last six months was high
      (44.2%). On average, in comparison with different specific localized types of
      single-site pain, the prevalence of multi-site pain was more common varying from
      13.2% in Armenia to 33.8% in Israel. Adolescent age and sex were strong
      predictors for reporting pain, but significantly different demographic patterns
      were found in the cross-country analyses. The most consistent findings indicate
      that multi-site pain was more prevalent among girls across all countries and that
      the prevalence increased with age. CONCLUSIONS: Internationally comparable data
      suggest that self-reported chronic pain among adolescents is highly prevalent,
      but different age and sex patterns across countries exist. Adolescents with
      chronic pain are not a homogenous group. Chronic pain co-occurrence and
      differences in chronic pain characteristics should be addressed in both clinical
      and public health practice for effective adolescent chronic pain management and
      prevention. SIGNIFICANCE: Chronic pain co-occurrence is common during adolescence
      across countries, the prevalence being among girls and in older age groups.
      Significant cross-country variations in the chronic pain prevalence and chronic
      pain patterns among adolescents exist. Significant country differences emerge for
      specific chronic pain patterns in association with adolescent demographics.

PMID- 30098108
TI  - Intermetalloid Clusters: Molecules and Solids in a Dialogue.
AB  - Atom-precise, ligand-stabilized metalloid clusters have emerged as outstanding
      model systems to study fundamental structure and bonding situations of
      compositionally related molecules and extended solid phases. However, this
      fascinating field of research is still largely restricted to homometallic and
      pseudo-heterometallic systems of closely related d-block metals. In this review,
      we will highlight our own and others' efforts to project the structural and
      compositional diversity of intermetallics with dissimilar d- and p-block metal
      combinations, particularly the Zintl and Hume-Rothery phases, onto the molecular
      level in order to bridge the still gaping chasm between heterometallic molecular
      coordination chemistry and solid-state intermetallics. Herein, fundamental
      synthetic approaches, as well as structural and electronic properties of thus
      accessible "molecular alloys" will be addressed, and placed against their
      exceptional position as intermediates on the way to nanomaterials.

PMID- 30098107
TI  - Exploring genetic modifiers of Gaucher disease: The next horizon.
AB  - Gaucher disease is an autosomal recessive lysosomal storage disorder resulting
      from mutations in the gene GBA1 that lead to a deficiency in the enzyme
      glucocerebrosidase. Accumulation of the enzyme's substrates, glucosylceramide and
      glucosylsphingosine, results in symptoms ranging from skeletal and visceral
      involvement to neurological manifestations. Nonetheless, there is significant
      variability in clinical presentations amongst patients, with limited correlation
      between genotype and phenotype. Contributing to this clinical variation are
      genetic modifiers that influence the phenotypic outcome of the disorder. In this
      review, we explore the role of genetic modifiers in Mendelian disorders and
      describe methods to facilitate their discovery. In addition, we provide examples
      of candidate modifiers of Gaucher disease, explore their relevance in the
      development of potential therapeutics, and discuss the impact of GBA1 and
      modifying mutations on other more common diseases like Parkinson disease.
      Identifying these important modulators of Gaucher phenotype may ultimately
      unravel the complex relationship between genotype and phenotype and lead to
      improved counseling and treatments.

PMID- 30098110
TI  - NAD(P)HX repair deficiency causes central metabolic perturbations in yeast and
      human cells.
AB  - NADHX and NADPHX are hydrated and redox inactive forms of the NADH and NADPH
      cofactors, known to inhibit several dehydrogenases in vitro. A metabolite repair
      system that is conserved in all domains of life and that comprises the two
      enzymes NAD(P)HX dehydratase and NAD(P)HX epimerase, allows reconversion of both
      the S- and R-epimers of NADHX and NADPHX to the normal cofactors. An inherited
      deficiency in this system has recently been shown to cause severe neurometabolic
      disease in children. Although evidence for the presence of NAD(P)HX has been
      obtained in plant and human cells, little is known about the mechanism of
      formation of these derivatives in vivo and their potential effects on cell
      metabolism. Here, we show that NAD(P)HX dehydratase deficiency in yeast leads to
      an important, temperature-dependent NADHX accumulation in quiescent cells with a
      concomitant depletion of intracellular NAD+ and serine pools. We demonstrate that
      NADHX potently inhibits the first step of the serine synthesis pathway in yeast.
      Human cells deficient in the NAD(P)HX dehydratase also accumulated NADHX and
      showed decreased viability. In addition, those cells consumed more glucose and
      produced more lactate, potentially indicating impaired mitochondrial function.
      Our results provide first insights into how NADHX accumulation affects cellular
      functions and pave the way for a better understanding of the mechanism(s)
      underlying the rapid and severe neurodegeneration leading to early death in NADHX
      repair-deficient children.

PMID- 30098109
TI  - TRIM44 promotes human esophageal cancer progression via the AKT/mTOR pathway.
AB  - Aberrant expression of TRIM-containing protein 44 (TRIM44) acts as a promoter in
      multiple cancers. Here, we investigated the biological functions and clinical
      significance of TRIM44 in human esophageal cancer (HEC). TRIM44 expression was
      significantly higher in HEC tissues than corresponding normal tissues at both the
      mRNA (2.42 +/- 0.52 vs 0.99 +/- 0.25) and protein (1.01 +/- 0.27 vs 0.30 +/-
      0.13) levels. Patients with high TRIM44 expression showed poor differentiation (P
      = 1.39 * 10-5 ), advanced TNM stage (P = 3.87 * 10-4 ) and, most importantly,
      significantly poorer prognosis (P = 2.80 * 10-5 ). TRIM44 played a crucial role
      in epithelial mesenchymal transition (EMT). A significant correlation was
      observed between TRIM44 and Ki67 expression. We demonstrated that TRIM44 markedly
      enhanced HEC cell proliferation, migration, and invasion. Additionally, TRIM44
      was involved in the AKT/mTOR signaling pathway and its downstream targets, such
      as STAT3 phosphorylation. Thus, elevated TRIM44 expression promotes HEC
      development by EMT via the AKT/mTOR pathway, and TRIM44 may be a novel prognostic
      indicator for HEC patients after curative resection.

PMID- 30098111
TI  - Nonpharmacological Interventions for Sleep Promotion on Preterm Infants in
      Neonatal Intensive Care Unit: A Systematic Review.
AB  - BACKGROUND: Nonpharmacological interventions are often used to promote sleep
      among preterm infants in the neonatal intensive care unit (NICU). However, there
      is a lack of synthesis in the evidence of their effectiveness. AIM: To synthesize
      the evidence on the effectiveness of nonpharmacological interventions on NICU
      preterm infants' sleep during hospital stay. METHODS: Seven databases were
      searched, including MEDLINE, EMBASE, Cochrane Central Register of Controlled
      Trials, Wan-fang database, China National Knowledge Infrastructure, China
      Biological Medicine Database, and VIP Journal Integration Platform from their
      inceptions to August 2017. Randomized controlled trials examining the effects of
      nonpharmacological interventions on preterm infants' sleep were included.
      RESULTS: This review included 36 studies. Nonpharmacological interventions
      included the Newborn Individualized Developmental Care and Assessment Program
      (NIDCAP), music, non-nutritive sucking, touch, cycled light, cobedding, rocking,
      oral sucrose, remolding mattresses, and family nurturing. The meta-analysis
      results showed that 1. the NIDCAP had no significant effect on total sleep time
      efficiency (TST%; p = .34); 2. mattress interventions had significant effects on
      TST% (p < .001); and active sleep efficiency (AS%; p = .006) but no significant
      effect on quiet sleep efficiency (QS%; p = .75); 3. cycled light increased TST (p
      = .02); and 4. cobedding had no significant effects on QS% and AS% (p = .63 and p
      = .88, respectively). LINKING EVIDENCE TO ACTION: Remolding mattresses and cycled
      light had significant effects on sleep promotion in preterm infants, but the
      quality of the evidence was very low. Further high-quality studies are needed to
      strengthen this evidence.

PMID- 30098112
TI  - The Adjective Rating Scale for Withdrawal: Validation of its ability to assess
      severity of prescription opioid misuse.
AB  - BACKGROUND: Withdrawal symptoms have been widely shown to be a useful indicator
      of the severity of opioid dependence. One of the most used instruments to assess
      them is the Adjective Rating Scale for Withdrawal (ARSW). However, there is a
      lack of adaptations and validations for its use with prescription opioids, even
      less for chronic pain patients under treatment with these analgesics. Thus, the
      aims of this study were to analyse the psychometric properties and invariance
      across gender of the ARSW in a sample of chronic noncancer pain patients.
      METHODS: Data were collected from 208 consumers of opioid medication, chronic
      noncancer pain patients. Participants completed sociodemographic, ARSW,
      prescription opioid dependence (DSM-IV-TR) and prescription opioid-use disorder
      (DSM-5) measurements. Gender invariance was assessed through multigroup
      confirmatory factor analysis (CFA). RESULTS: The ARSW showed a unidimensional
      factor structure and high internal consistency (Cronbach's alpha = 0.85).
      Multigroup CFA showed configural, metric, scalar and strict invariances of ARSW
      across gender. Predictive validity analyses indicated that ARSW has good capacity
      for identifying the severity of prescription opioid-use disorder, using both DSM
      IV-TR and DSM-5 criteria. CONCLUSIONS: These findings show that the ARSW is a
      valid and reliable tool for use in the assessment of the withdrawal of
      prescription opioids in chronic pain patients under treatment with these
      analgesics, regardless of their gender. SIGNIFICANCE: Findings supported the
      reliability and validity of the ARSW to assess withdrawal of prescription opioids
      in individuals with chronic noncancer pain. The instrument can be applied
      indistinctly in men and women. An increase in the ARSW scores could be used as an
      indicator of potential risk of prescription opioid-use disorder during long-term
      treatments.

PMID- 30098113
TI  - Endoscopic approach in one hundred and seventy-nine patients of
      dacryocystorhinostomy.

PMID- 30098114
TI  - Varying 10-year off-treatment responses to nucleos(t)ide analogues in patients
      with chronic hepatitis B according to their pretreatment hepatitis B e antigen
      status.
AB  - OBJECTIVE: To evaluate the long-term durability and efficacy of nucleos(t)ide
      analogues (NAs) and to determine the related factors for virological relapse in
      chronic hepatitis B (CHB) patients. METHODS: CHB patients who fulfilled the
      criteria for discontinuing NAs therapy in accordance with the published
      guidelines were included in the study from December 2001. Virological relapse was
      defined as serum hepatitis virus B (HBV) DNA >104 copies/mL twice at least 2
      weeks apart. RESULTS: A total of 223 CHB patients were enrolled at the time their
      NAs therapy was discontinued. The 10-year cumulative relapse rate (CRR) in
      hepatitis B e antigen (HBeAg)-positive patients was statistically lower than that
      in HBeAg-negative patients (30.9% vs 62.3%, P < 0.001). In the HBeAg-positive
      group, Cox regression analysis showed that age at cessation (hazard ratio [HR]
      1.067, P < 0.001), consolidation therapy (HR 0.958, P = 0.021), and time to HBeAg
      seroconversion (HR 0.943, P = 0.019) were predictors for relapse. In the HBeAg
      negative group, age at cessation (HR 1.040, P = 0.004) and time to HBV DNA
      negativity (HR 1.246, P = 0.010) were potential predictors for virological
      relapse. CONCLUSIONS: The off-treatment responses to NAs differ in CHB patients
      with different pretreatment HBeAg status. NA withdrawal is generally safe and
      feasible in young patients with CHB. Long consolidation periods should be
      preferred in HBeAg-positive patients to achieve better durability. Benefits of
      cessation of NAs do not last long in HBeAg-negative CHB patients.

PMID- 30098115
TI  - Optical windows for head tissues in near-infrared and short-wave infrared
      regions: Approaching transcranial light applications.
AB  - Optical properties of the rat head tissues (brain cortex, cranial bone and scalp
      skin) are assessed, aiming at transcranial light applications such as optical
      imaging and phototherapy. The spectral measurements are carried out over the wide
      spectral range of 350 to 2800 nm, involving visible, near-infrared (NIR) and
      short-wave infrared (SWIR) regions. Four tissue transparency windows are
      considered: ~700 to 1000 nm (NIR-I), ~1000 to 1350 nm (NIR-II), ~1550 to 1870 nm
      (NIR-III or SWIR) and ~2100 to 2300 nm (SWIR-II). The values of attenuation
      coefficient and total attenuation length are determined for all windows and
      tissue types. The spectra indicate transmittance peaks in NIR, NIR-II and SWIR
      II, with maximum tissue permeability for SWIR light. The use of SWIR-II window
      for the transcranial light applications is substantiated. Furthermore, absorbance
      of the head tissues is investigated in details, by defining and describing the
      characteristic absorption peaks in NIR-SWIR.

PMID- 30098116
TI  - Don't be stumped by the stent: transanal total mesorectal excision in the
      resection of a stented rectal cancer - a video vignette.

PMID- 30098117
TI  - Modified fibrescope guided nasogastric tube insertion: Our experience with 23
      patients.

PMID- 30098118
TI  - Dual-Axial Gradient Doping (Zr and Sn) on Hematite for Promoting Charge
      Separation in Photoelectrochemical Water Splitting.
AB  - One of the crucial challenges to enhance the photoelectrochemical water-splitting
      performance of hematite (alpha-Fe2 O3 ) is to resolve its very fast charge
      recombination in bulk. Herein, we describe the design and fabrication of dual
      axial gradient-doping on 1D Fe2 O3 nanorod arrays with Zr doping for x-axial and
      Sn doping for y-axial directions to promote the charge separation. This dual
      axial gradient-doping structure fulfills the requirements of a greater electron
      carrier concentration for increasing conductivity as well as a higher charge
      separation efficiency across the dual-axial direction of Fe2 O3 nanorods,
      ultimately showing an excellent photocurrent density of 1.64 mA cm-2 at 1.23 V
      vs. RHE, which is 26.3 times more than that of the bare Fe2 O3 . Furthermore, the
      remarkably improved photocurrent density, when comparing the uniform Zr-doped Fe2
      O3 nanorod arrays (1.0 mA cm-2 at 1.23 V vs. RHE) with dual-axial gradient-doped
      (Zr and Sn) Fe2 O3 nanorod arrays, highlights the additional charge-separation
      effect resulting from gradient codoping of Zr and Sn. Hence, this promising
      design may provide guidelines for dual-axial gradient doping into photoelectrodes
      to realize efficient PEC water splitting.

PMID- 30098119
TI  - Spectral correction for handheld optoacoustic imaging by means of near-infrared
      optical tomography in reflection mode.
AB  - In vivo imaging of tissue/vasculature oxygen saturation levels is of prime
      interest in many clinical applications. To this end, the feasibility of combining
      two distinct and complementary imaging modalities is investigated: optoacoustics
      (OA) and near-infrared optical tomography (NIROT), both operating noninvasively
      in reflection mode. Experiments were conducted on two optically heterogeneous
      phantoms mimicking tissue before and after the occurrence of a perturbation. OA
      imaging was used to resolve submillimetric vessel-like optical absorbers at
      depths up to 25 mm, but with a spectral distortion in the OA signals. NIROT
      measurements were utilized to image perturbations in the background and to
      estimate the light fluence inside the phantoms at the wavelength pair (760 nm,
      830 nm). This enabled the spectral correction of the vessel-like absorbers' OA
      signals: the error in the ratio of the absorption coefficient at 830 nm to that
      at 760 nm was reduced from 60%-150% to 10%-20%. The results suggest that oxygen
      saturation (SO 2 ) levels in arteries can be determined with <10% error and
      furthermore, that relative changes in vessels' SO 2 can be monitored with even
      better accuracy. The outcome relies on a proper identification of the OA signals
      emanating from the studied vessels.

PMID- 30098120
TI  - Effect of positioning on ureteric stone retropulsion: 'gravity works'.
AB  - OBJECTIVE: To evaluate the potential impact of alterations in 'patient' position
      on laser-induced ureteric stone retropulsion in an in vitro model. MATERIALS AND
      METHODS: A ceramic (phantom) stone was placed in a water-filled clear polymer
      tube and subjected to continuous laser energy until the stone had retropulsed a
      distance of 10 cm. The trial was stopped after 60 s if the stone had not reached
      10 cm. The time and total energy needed to cause 10 cm of retropulsion were
      recorded at incline angles of 0 degrees , 10 degrees , 20 degrees , and 40
      degrees ; 10 trials at each angle were completed. The study was then repeated
      with pure calcium phosphate brushite stones. RESULTS: Retropulsion decreased with
      increasing incline angle of the saline-filled clear polymer tube. At 0 degrees 
      of incline the phantom stone reached a distance of 10 cm after 7.4 s. At 10
      degrees , 20 degrees  and 40 degrees , the phantom stone migrated a mean maximum
      distance of 3.1, 1.2 and 0.7 cm, respectively, and the trial was stopped after 60
      s. For the calcium phosphate stone, at 0 degrees  and 10 degrees  of incline, the
      stone reached 10 cm after 6.9 and 42.8 s, respectively (P < 0.05). At 20 degrees 
      and 40 degrees , the calcium phosphate stone moved a mean maximum distance of 2.4
      and 1 cm, and the trial was stopped after 60 s. CONCLUSION: Alterations in the
      angle of inclination reduced stone retropulsion during ureteroscopic lithotripsy
      in an in vitro model to <1 cm. Increasing the incline angle of a patient may
      effectively preclude retropulsion when performing laser lithotripsy of ureteric
      stones.

PMID- 30098121
TI  - Population attributable fractions of the main type 2 diabetes mellitus risk
      factors in women: Findings from the French E3N cohort.
AB  - BACKGROUND: Although many type 2 diabetes mellitus (T2DM) risk factors have been
      identified, little is known regarding their contributions to the diabetes burden
      at the population level. METHODS: The study included 72 655 French women from the
      Etude Epidemiologique de Femmes de la Mutuelle Generale de l'Education Nationale
      (E3N) prospective cohort followed between 1993 and 2011. Cox multivariable models
      including the main T2DM risk factors (metabolic, dietary, clinical, socioeconomic
      and hormonal) and a healthy lifestyle index combining five characteristics
      (smoking, body mass index [BMI], alcohol consumption, fruit and vegetable
      consumption, and physical activity) were used to estimate hazard ratios and
      population attributable fractions (PAFs) for T2DM. RESULTS: In multivariate
      models, factors with the strongest effect on T2DM risk were, in decreasing order,
      BMI >= 30 kg/m2 (PAF = 43%; 95% confidence interval [CI] 37-47), high adherence
      to a Western dietary pattern (PAF = 30%; 95% CI 20-40), hypertension (PAF = 26%;
      95% CI 20-32), an acidogenic diet (PAF = 24%; 95% CI 16-32), a family history of
      diabetes (PAF = 20%; 95% CI 17-22), and, with a negative correlation, moderate
      alcohol consumption (PAF-19%; 95% CI -34, -4). The PAF for an unhealthy lifestyle
      was 57% (95% CI 50-63). CONCLUSIONS: We have been able to sort out and quantify
      the effect of various dietary and biological T2DM risk factors simultaneously in
      a single population, and to highlight the importance of a healthy lifestyle for
      primary prevention: more than half the T2DM cases could have been prevented
      through a healthier lifestyle.

PMID- 30098123
TI  - Automated classification of osteomeatal complex inflammation on computed
      tomography using convolutional neural networks.
AB  - BACKGROUND: Convolutional neural networks (CNNs) are advanced artificial
      intelligence algorithms well suited to image classification tasks with variable
      features. These have been used to great effect in various real-world applications
      including handwriting recognition, face detection, image search, and fraud
      prevention. We sought to retrain a robust CNN with coronal computed tomography
      (CT) images to classify osteomeatal complex (OMC) occlusion and assess the
      performance of this technology with rhinologic data. METHODS: The Google
      Inception-V3 CNN trained with 1.28 million images was used as the base model.
      Preoperative coronal sections through the OMC were obtained from 239 patients
      enrolled in 2 prospective chronic rhinosinusitis (CRS) outcomes studies, labeled
      according to OMC status, and mirrored to obtain a set of 956 images. Using this
      data, the classification layer of Inception-V3 was retrained in Python using a
      transfer learning method to adapt the CNN to the task of interpreting sinonasal
      CT images. RESULTS: The retrained neural network achieved 85% classification
      accuracy for OMC occlusion, with a 95% confidence interval for algorithm accuracy
      of 78% to 92%. Receiver operating characteristic (ROC) curve analysis on the test
      set confirmed good classification ability of the CNN with an area under the ROC
      curve (AUC) of 0.87, significantly different than both random guessing and a
      dominant classifier that predicts the most common class (p < 0.0001). CONCLUSION:
      Current state-of-the-art CNNs may be able to learn clinically relevant
      information from 2-dimensional sinonasal CT images with minimal supervision.
      Future work will extend this approach to 3-dimensional images in order to further
      refine this technology for possible clinical applications.

PMID- 30098122
TI  - Lyotropic Chromonic Mesophases Derived from Metal-Organic Complexes.
AB  - Lyotropic chromonic (LC) mesophases have received a large amount of attention,
      owing to the semi-stable nature of the chromonics. In these systems, the balance
      between the ordering forces and the thermal motion is delicate. As such,
      temperature changes, concentration variations, alterations to the electric and
      magnetic fields, and the addition of additives to the chromonic systems can be
      sensitively monitored. Herein, we review the general characterization methods for
      lyotropic chromonic mesophases, including polarized optical microscopy (POM),
      multinuclear NMR spectroscopy, X-ray diffractometry, cryo-TEM, and rheology. In
      recent years, lyotropic chromonic mesophases that are derived from metal-organic
      complexes have become established and offer the possibility of introducing the
      rich functionalities of the metal complexes into these systems. The chromonic
      properties, aggregation behaviors, and influence factors on such systems are
      reviewed case-by-case. Finally, preliminary attempts to utilize these systems are
      reviewed, which have demonstrated their potential application in optical devices,
      biosensing, luminescent materials, etc.

PMID- 30098124
TI  - Transition experiences between hospital- and home-care for parents of children
      with hypoplastic left heart syndrome.
AB  - PURPOSE: Children with hypoplastic left heart syndrome (HLHS) experience numerous
      vulnerabilities during transitions from hospital to home during their first year
      of life. This paper examines the parents' responses to the situations they
      experience during the initial interstage transition as described through illness
      blogs. DESIGN AND METHODS: A qualitative descriptive design through inductive
      theme development using thematic analysis was performed for this study. Text data
      were used from publically available blogs written by parents of HLHS children on
      their feelings and experiences during transitions between hospital- and home-care
      during the interstage period. RESULTS: Six blogs were analyzed. Overall, the lack
      of difference in normalcy for these parents and their families was apparent.
      Major themes included: thoughts and feelings when discharged from the hospital,
      difficulties with hospital readmissions, protecting their child from infection,
      and developing a support system. CONCLUSIONS: Parents looked forward to going
      home and learned all they could about properly caring for their child before
      going home. They were disappointed and frustrated when returning to the hospital
      for either emergency or scheduled admissions and were not prepared to see their
      child in the intensive care unit environment again. Many parents isolated
      themselves and avoided the hospital as much as possible to avoid their child
      developing an infection. All parents had support systems through family and/or
      friends and found an unexpected sense of support through their blog families.

PMID- 30098125
TI  - Quantitative assessment of changes in anterior segment morphology after argon
      laser peripheral iridoplasty: findings from the EARL study group.
AB  - IMPORTANCE: Argon laser peripheral iridoplasty (ALPI) could be effective in
      widening residual angle closure following laser peripheral iridotomy (LPI).
      BACKGROUND: We investigated changes in angle parameters following ALPI and its
      safety profile in this study. DESIGN: Retrospective, observational case series.
      PARTICIPANTS: The records from a single centre, of 36 patients (60 eyes) who
      underwent ALPI, for residual angle closure following LPI, were reviewed. METHODS:
      We analysed anterior chamber parameters in anterior segment optical coherence
      tomography (ASOCT) images using customized software pre- and post-ALPI. Paired t
      test was used to compare changes. MAIN OUTCOME MEASURES: ASOCT parameters
      analysed included angle opening distance (AOD 500 and 750), trabecular iris
      surface area (TISA 500 and 750), anterior chamber width (ACW), anterior chamber
      volume (ACV), angle recess area (ARA), anterior chamber area (ACA), anterior
      chamber depth (ACD) and lens vault (LV). RESULTS: There was a mean increase in
      AOD 500 (0.05 vs. 0.16 mm, P < 0.001), AOD 750 (0.15 vs. 0.27 mm, P < 0.001),
      TISA 500 (0.010 vs. 0.038 mm2 , P < 0.001), TISA 750 (0.039 vs. 0.102 mm2 , P <
      0.001), ACV (89.76 vs. 102.25 mm3 , P = 0.01), ARA 500 (0.015 vs. 0.033 mm2 , P <
      0.001) and ARA 750 (0.044 vs. 0.088 mm2 , P < 0.001). There was no significant
      change in ACW, ACD, ACA and LV. Mean intraocular pressure (IOP) decreased post
      ALPI (17.2 vs. 15.7 mmHg, P = 0.002). The mean follow-up duration was 2.1 years
      (range 0.5-5 years). CONCLUSIONS AND RELEVANCE: ALPI results in changes to the
      angle morphology and lowered IOP in eyes with residual angle closure. Our
      findings suggest a possible role for ALPI in eyes with residual angle closure
      following peripheral iridotomy.

PMID- 30098126
TI  - The effects of dietary supplementation with inulin and inulin-propionate ester on
      hepatic steatosis in adults with non-alcoholic fatty liver disease.
AB  - The short chain fatty acid (SCFA) propionate, produced through fermentation of
      dietary fibre by the gut microbiota, has been shown to alter hepatic metabolic
      processes that reduce lipid storage. We aimed to investigate the impact of
      raising colonic propionate production on hepatic steatosis in adults with non
      alcoholic fatty liver disease (NAFLD). Eighteen adults were randomized to receive
      20 g/d of an inulin-propionate ester (IPE), designed to deliver propionate to the
      colon, or an inulin control for 42 days in a parallel design. The change in
      intrahepatocellular lipid (IHCL) following the supplementation period was not
      different between the groups (P = 0.082), however, IHCL significantly increased
      within the inulin-control group (20.9% +/- 2.9% to 26.8% +/- 3.9%; P = 0.012; n =
      9), which was not observed within the IPE group (22.6% +/- 6.9% to 23.5% +/-
      6.8%; P = 0.635; n = 9). The predominant SCFA from colonic fermentation of inulin
      is acetate, which, in a background of NAFLD and a hepatic metabolic profile that
      promotes fat accretion, may provide surplus lipogenic substrate to the liver. The
      increased colonic delivery of propionate from IPE appears to attenuate this
      acetate-mediated increase in IHCL.

PMID- 30098128
TI  - A miniaturized solid-phase extraction adsorbent of calix[4]arene-functionalized
      graphene oxide/polydopamine-coated cellulose acetate for the analysis of
      aflatoxins in corn.
AB  - A calix[4]arene-functionalized graphene oxide/polydopamine-coated cellulose
      acetate adsorbent was fabricated for the pre-concentration of aflatoxins. The
      highly porous developed adsorbent does not produce the high backpressure that
      normally occurs in particle-packed cartridges and its large surface area helps to
      improve adsorption. The highly efficient adsorption of aflatoxins by the hybrid
      adsorbent is facilitated via hydrogen bonding and hydrophobic and pi-pi
      interactions. Polymerization time, amount of calix[4]arene-functionalized
      graphene oxide, type and volume of desorption solvent, sample pH, sample volume,
      and sample flow rate were optimized. The linearity of aflatoxin B1 was in the
      range of 0.01-10.0 MUg/kg, aflatoxin B2 was in the range of 0.02-10.0 MUg/kg and
      aflatoxin G1 and aflatoxin G2 were in the range of 0.050-10.0 MUg/kg. The limits
      of detection were 0.01 MUg/kg for aflatoxin B1, 0.02 MUg/kg for aflatoxin B2 and
      0.05 MUg/kg for aflatoxin G1 and aflatoxin G2. The developed calix[4]arene
      functionalized graphene oxide/polydopamine-coated cellulose acetate adsorbent was
      successfully utilized for the analysis of aflatoxins from corn samples and the
      extraction efficiency was satisfactory with obtained recoveries from 83.0 to
      106.7%. Moreover, fabricated adsorbent is easy to prepare, inexpensive, and can
      be reused.

PMID- 30098127
TI  - The effect of mandelonitrile, a recently described salicylic acid precursor, on
      peach plant response against abiotic and biotic stresses.
AB  - In a previous work, we observed that mandelonitrile (MD), which controls
      cyanogenic glycoside turnover, is involved in salicylic acid (SA) biosynthesis in
      peach plants. In order to gain knowledge about the possible roles of this SA
      biosynthetic pathway, this current study looks at the effect of MD and
      phenylalanine (Phe; MD precursor) treatments on peach plant performance from an
      agronomic point of view. Abiotic (2 g.l-1 NaCl) and biotic (Plum pox virus, PPV)
      stresses were assayed. We recorded the following chlorophyll fluorescence
      parameters: quantum yield of photochemical energy conversion in PSII [Y(II)],
      photochemical quenching (qP) and quantum yield of regulated non-photochemical
      energy loss in PSII and its coefficient [Y(NPQ) and qN]. In addition, considering
      that environmental stresses lead to nutritional disorders, we determined the
      soluble K+ , Ca2+ , Na+ and Cl- concentrations in NaCl-stressed seedlings. In PPV
      infected seedlings, we recorded the Ca2+ level, which has been suggested to play
      critical roles in regulating SA-related plant defence responses against
      pathogens. The MD treatment lessened the effect of both stresses on plant
      development. In addition, an increase in non-photochemical quenching parameters
      was observed in MD-treated seedlings, suggesting a safer dissipation of excess
      energy under stress conditions. In NaCl-stressed peach seedlings both treatments
      stimulated the accumulation of phytotoxic ions in roots, whereas in PPV-infected
      seedlings MD increased Ca2+ content. Our results suggest that MD and Phe
      influence the response of peach seedlings to the deleterious effects of salt and
      PPV infection stresses.

PMID- 30098129
TI  - Carbohydrate quantity in the dietary management of type 2 diabetes: A systematic
      review and meta-analysis.
AB  - AIMS: This systematic review and meta-analysis (registration number:
      CRD42013005825) compares the effects of low carbohydrate diets (LCDs) on body
      weight, glycaemic control, lipid profile and blood pressure with the effects of
      higher carbohydrate diets (HCDs) in adults with type 2 diabetes. METHODS:
      MEDLINE, EMBASE, CENTRAL, CINAHL, Food Science Source and SweMed+ databases were
      systematically searched to identify randomized controlled trials (duration >=3
      months) investigating the effects of an LCD compared to an HCD in the management
      of type 2 diabetes. Data were extracted and pooled using a random effects model
      and were expressed as mean differences and risk ratio. Subgroup analyses were
      undertaken to examine the effects of duration of intervention, extent of
      carbohydrate restriction and risk of bias. The certainty of evidence was assessed
      using GRADE. RESULTS: Of the 1589 studies identified, 23, including 2178
      participants, met inclusion criteria. Reductions were slightly greater with LCDs
      than with HCDs for HbA1c (-1.0 mmol/mol; CI, -1.9, -0.1 [-0.09%; CI, -0.17, 
      0.01]) and for triglycerides (-0.13 mmol/L; CI, -0.24, -0.02). Changes in weight,
      HDL- and LDL-cholesterol, total cholesterol and blood pressure did not differ
      significantly between groups. Subgroup analyses suggested that the difference in
      HbA1c was evident only in studies with a duration of <=6 months and with a high
      risk of bias. CONCLUSIONS: The proportion of daily energy provided by
      carbohydrate intake is not an important determinant of response to dietary
      management, especially when considering longer term trials. A range of dietary
      patterns, including those traditional in Mediterranean countries, seems suitable
      for translating nutritional recommendations for individuals with diabetes into
      practical advice.

PMID- 30098130
TI  - Laparoscopic Hartmann's reversal after laparoscopic Hartmann's procedure for
      Hinchey III diverticulitis: a surprisingly difficult rectal stump dissection - a
      video vignette.

PMID- 30098131
TI  - Has the increasing incidence of chlamydia and gonorrhoea resulted in increased
      chlamydial and gonococcal conjunctivitis presentations? Results from Melbourne,
      Australia, from 2000 to 2017.

PMID- 30098132
TI  - Clopidogrel-associated genetic variants on inhibition of platelet activity and
      clinical outcome for acute coronary syndrome patients.
AB  - Acute coronary syndrome (ACS) has become a vital disease with high mortality
      worldwide. A combined antiplatelet therapy (aspirin and a P2Y12 antagonist) is
      commonly used to prevent re-infarction in ACS patients who have undergone
      percutaneous coronary intervention (PCI). Clopidogrel, a P2Y12 antagonist, plays
      an important role in the inhibition of platelet aggregation (IPA). However, it is
      a pro-drug requiring biotransformation by cytochrome P450 (CYP450). The aim of
      this study is to unravel the effect of clopidogrel-associated genetic variants on
      inhibition of platelet activity and clinical outcomes in ACS patients. In our
      study, a total of 196 patients with metabolic gene polymorphism of clopidogrel
      were enrolled, and their antiplatelet effect as well as their cardiovascular
      events were collected. Approximately 2 mL of venous blood samples were used for
      genotype detection and another 4 mL were collected for platelet reactivity with
      thrombelastography. The primary clinical end-point was defined as a combination
      of cardiovascular mortality and revascularization for targeted vascular lesion.
      Based on the results of IPA, the prevalence of high on-treatment platelet
      reactivity (HPR) was 17.3% and the majority of patients (82.7%) obtained normal
      on-treatment platelet reactivity (NPR). The HPR group had significantly higher
      body mass index (BMI) and lower arachidonic acid (AA) induced IPA (P < 0.05).
      Therapy including Glycoprotein (GP) IIb/IIIa antagonist increased IPA (P < 0.05).
      ADP-induced IPA effect was lower with the presence of CYP2C19*2, *3 and
      paraoxonase (PON)1 Q192R loss-of-function (LOF) alleles, respectively (P < 0.05).
      Multivariate logistic regression analysis demonstrated that aspirin resistance
      (AA-induced IPA < 50%) had a greater risk of the occurrence of major adverse
      cardiovascular events (MACE) (OR = 3.817; 95% CI: 1.672-8.700; P = 0.002).
      CYP2C19*2 LOF alleles were associated with high risk of MACE in 1-year post PCI
      operations (OR = 2.571; 95% CI: 1.143-5.780; P = 0.030). For the ACS patients,
      the presence of CYP2C19*2 and PON1 Q192R LOF alleles were the major drivers of
      HPR.

PMID- 30098133
TI  - Reply by Bell et al.

PMID- 30098134
TI  - Brain glucose uptake is associated with endogenous glucose production in obese
      patients before and after bariatric surgery and predicts metabolic outcome at
      follow-up.
AB  - AIMS: To investigate further the finding that insulin enhances brain glucose
      uptake (BGU) in obese but not in lean people by combining BGU with measures of
      endogenous glucose production (EGP), and to explore the associations between
      insulin-stimulated BGU and peripheral markers, such as metabolites and
      inflammatory markers. MATERIALS AND METHODS: A total of 20 morbidly obese
      individuals and 12 lean controls were recruited from the larger randomized
      controlled SLEEVEPASS study. All participants were studied under fasting and
      euglycaemic hyperinsulinaemic conditions using fluorodeoxyglucose-positron
      emission tomography. Obese participants were re-evaluated 6 months after
      bariatric surgery and were followed-up for ~3 years. RESULTS: In obese
      participants, we found a positive association between BGU and EGP during insulin
      stimulation. Across all participants, insulin-stimulated BGU was associated
      positively with systemic inflammatory markers and plasma levels of leucine and
      phenylalanine. Six months after bariatric surgery, the obese participants had
      achieved significant weight loss. Although insulin-stimulated BGU was decreased
      postoperatively, the association between BGU and EGP during insulin stimulation
      persisted. Moreover, high insulin-stimulated BGU at baseline predicted smaller
      improvement in fasting plasma glucose at 2 and 3 years of follow-up. CONCLUSIONS:
      Our findings suggest the presence of a brain-liver axis in morbidly obese
      individuals, which persists postoperatively. This axis might contribute to
      further deterioration of glucose homeostasis.

PMID- 30098135
TI  - High-performance, robustly verified Monte Carlo simulation with FullMonte.
AB  - We introduce the FullMonte tetrahedral 3-D Monte Carlo (MC) software package for
      simulation, visualization, and analysis of light propagation in heterogeneous
      turbid media including tissue. It provides the highest computational performance
      and richest set of input, output, and analysis facilities of any open-source
      tetrahedral-mesh MC light simulator. It also provides a robust framework for
      statistical verification. A scripting interface makes set-up of simulation runs
      simple, including parameter sweeps, while simultaneously providing customization
      options. Data formats shared with class-leading visualization tools, VTK and
      Paraview, facilitate interactive generation of publication-quality fluence and
      irradiance maps. The simulator can read and write file formats supported by other
      similar simulators, such as TIM-OS, MMC, COMSOL (finite-element simulations), and
      MCML to support comparison. Where simulator features permit, FullMonte can take a
      single test case, run it in multiple software packages, and load the results
      together for comparison. Example meshes, optical properties, set-up scripts, and
      output files are provided for user convenience. We demonstrate its use in several
      test cases, including photodynamic therapy of the brain, bioluminescence imaging
      (BLI) in a mouse phantom, and a comparison against MCML for layered geometries.
      Application domains that can benefit from use of FullMonte include photodynamic,
      photothermal, and photobiomodulation therapies, BLI, diffuse optical tomography,
      MC software development, and biophotonics education. Since MC results may be used
      for preclinical or even clinical experiments, a robust and rigorous verification
      process is essential. Being a stochastic numerical method, MC simulation has
      unique challenges associated with verification of output results since observed
      differences may be due simply to output variance or actual differences in
      expected output. We describe and have implemented a rigorous and statistically
      justified framework for comparing between simulators of the same class and for
      performing regression testing.

PMID- 30098138
TI  - Biomechanical Analysis of Augments in Revision Total Knee Arthroplasty.
AB  - Augments are a common solution for treating bone loss in revision total knee
      arthroplasty and industry is providing to surgeons several options, in terms of
      material, thickness and shapes. Actually, while the choice of the shape and the
      thickness is mainly dictated by the bone defect, no proper guidelines are
      currently available to select the optimal material for a specific clinical
      situation. Nevertheless, different materials could induce different bone
      responses and, later, potentially compromise implant stability and performances.
      Therefore, in this study, a biomechanical analysis is performed by means of
      finite element modelling about existing features for augment designs. Based upon
      a review of available products at present, the following augments features were
      analyzed: position (distal/proximal and posterior), thickness (5, 10 and 15 mm)
      and material (bone cement, porous and solid metal). For all analyzed
      configurations, bone stresses were investigated in different regions and compared
      among all configurations and the control model for which no augments were used.
      Results show that the use of any kind of augment usually induces a change in bone
      stresses, especially in the region close to the bone cut. The porous metal
      presents result very close to cement ones; thus it could be considered as a good
      alternative for defects of any size. Solid metal has the least satisfying results
      inducing the highest changes in bone stress. The results of this study
      demonstrate that material stiffness of the augment should be as close as possible
      to bone properties for allowing the best implant performances.

PMID- 30098136
TI  - Doxycycline Attenuates Atrial Remodeling by Interfering with MicroRNA-21 and
      Downstream Phosphatase and Tensin Homolog (PTEN)/Phosphoinositide 3-Kinase (PI3K)
      Signaling Pathway.
AB  - BACKGROUND Atrial remodeling especially in the form of fibrosis is the most
      important substrate of atrial fibrillation (AF). The aim of this study was to
      investigate the effects of doxycycline on chronic intermittent hypoxia (CIH)
      induced atrial remodeling and the pathophysiological mechanisms underlying such
      changes. MATERIAL AND METHODS A total of 30 Sprague-Dawley rats were randomized
      into 3 groups: Control group, CIH group, and CIH with doxycycline treatment
      group. CIH rats were subjected to CIH 6 h/d for 30 days and treatment rats were
      administrated doxycycline while they received CIH. After the echocardiography
      examination, rats were sacrificed at 31 days. The tissues of atria were collected
      for histological and molecular biological experiments, Masson staining was used
      to evaluate the extent of atrial fibrosis, microRNA-21, and its downstream target
      phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K) were
      assessed. RESULTS Compared to the control group, the CIH rats showed higher
      atrial interstitial collagen fraction, increased microRNA-21, PI3K levels, and
      decreased PTEN levels. Doxycycline treatment attenuated CIH-induced atrial
      fibrosis, reduced microRNA-21 and PI3K, and increased PTEN. CONCLUSIONS CIH
      induced significant atrial remodeling, which was attenuated by doxycycline in our
      rat model. These changes may be explained due to alterations in the microRNA-21
      related signaling pathways by doxycycline.

PMID- 30098137
TI  - Computational fluid dynamic study for aTAA hemodynamics: an integrated image
      based and RBF mesh morphing approach.
AB  - We present a novel framework for the fluid dynamics analysis of healthy subjects
      and patients affected by ascending thoracic aorta aneurysm (aTAA). Our aim is to
      obtain indications about the effect of a bulge on the hemodynamic environment at
      different enlargements. 3D surface models defined from healthy subjects and
      patients with aTAA, selected for surgical repair, were generated. A
      representative shape model for both healthy and pathological groups has been
      identified. A morphing technique based on radial basis functions (RBF) was
      applied to mould the shape relative to healthy patient into the representative
      shape of aTAA dataset to enable the parametric simulation of the aTAA formation.
      CFD simulations were performed by means of a finite volume solver using the mean
      boundary conditions obtained from three-dimensional (PC-MRI) acquisition. Blood
      flow helicity and flow descriptors were assessed for all the investigated models.
      The feasibility of the proposed integrated approach of RBF morphing technique and
      CFD simulation for aTAA was demonstrated. Significant hemodynamic changes appear
      at the 60% of the bulge progression. An impingement of the flow toward the bulge
      was observed by analyzing the normalized flow eccentricity index.

PMID- 30098139
TI  - The "Curse" of the Fellow Eye in Glaucoma.

PMID- 30098140
TI  - Cocaine-Induced Midline Destructive Lesions Associated With Erosion of the
      Eustachian Tube.

PMID- 30098141
TI  - MUC16 Mutations and Prognosis in Gastric Cancer: A Little Goes a Long Way.

PMID- 30098142
TI  - Sensitivity analysis of the estimated muscle forces during gait with respect to
      the musculoskeletal model parameters and dynamic simulation techniques.
AB  - The purpose of the current study was to investigate the robustness of dynamic
      simulation results in the presence of uncertainties resulting from application of
      a scaled-generic musculoskeletal model instead of a subject-specific model as
      well as the effect of the choice of simulation method on the obtained muscle
      forces. The performed sensitivity analysis consisted of the following multibody
      parameter modifications: maximum isometric muscle forces, number of muscles, the
      hip joint centre location, segment masses as well as different dynamic simulation
      methods, namely static optimization with three different criteria and a computed
      muscle control algorithm (hybrid approach combining forward and inverse
      dynamics). Twenty-four different models and fifty-five resultant dynamic
      simulation data sets were analysed. The effects of model perturbation on the
      magnitude and profile of muscle forces were compared. It has been shown that
      estimated muscle forces are very sensitive to model parameters. The greatest
      impact was observed in the case of the force magnitude of the muscles generating
      high forces during gait (regardless of the modification introduced). However, the
      force profiles of those muscles were preserved. Relatively large differences in
      muscle forces were observed for different simulation techniques, which included
      both magnitude and profile of muscle forces. Personalization of model parameters
      would affect the resultant muscle forces and seems to be necessary to improve
      general accuracy of the estimated parameters. However, personalization alone will
      not ensure high accuracy due to the still unresolved muscle force sharing
      problem.

PMID- 30098144
TI  - Unilateral Eyelid Swelling With Submandibular Lymph Node Enlargement.

PMID- 30098143
TI  - Genetic Penetrance of Macular Telangiectasia Type 2.
AB  - Importance: The apparent genetic penetrance of macular telangiectasia type 2
      (MacTel) is important for gene discovery studies and for clinical risk assessment
      of affected individuals' family members. Objective: To determine the genetic
      penetrance of MacTel. Design, Setting, and Participants: Descriptive cross
      sectional study of patients with MacTel at a tertiary referral eye center. From
      2008 to 2016, consecutive patients with MacTel were independently identified, and
      all of their available siblings and parents were recruited. Seventeen probands
      with MacTel were included in the study who satisfied the requirement of having at
      least 1 parent or sibling willing and able to participate. Data from these 17
      families were included for the analysis of apparent genetic penetrance. Main
      Outcomes and Measures: Determination of MacTel genetic penetrance in probands'
      parents and siblings. Results: Of 80 study participants, 50 (62.5%) were women.
      The mean (SD) age of study participants with MacTel was 61.2 (14.0) years (range,
      23-81 years) and without MacTel was 60.7 (16.4) years (range, 24-92 years). There
      were 17 MacTel probands, and there was a high rate of enrollment of living
      siblings and parents: 52 of 71 living siblings (73%) and 11 of 12 parents (92%).
      Of 52 enrolled siblings, 9 (17%) were affected. Of 11 enrolled parents, 3 (27%)
      had MacTel. Apparent genetic penetrance was calculated to be 0.35 (95% CI, 0.14
      0.6) by sibling analysis and 0.55 (95% CI, 0.02-1.00) by parent analysis.
      Combining the sibling and parent analyses, the apparent penetrance was calculated
      to be 0.38 (95% CI, 0.19-0.57). Conclusions and Relevance: The genetic penetrance
      of MacTel in rigorously phenotyped multiple large families is described. Families
      such as these could be critical for successful identification of MacTel genes.

PMID- 30098145
TI  - Effect of Longitudinal Variation of Vocal Fold Inner Layer Thickness on Fluid
      Structure Interaction During Voice Production.
AB  - A three-dimensional fluid-structure interaction computational model was used to
      investigate the effect of the longitudinal variation of vocal fold inner layer
      thickness on voice production. The computational model coupled a finite element
      method based continuum vocal fold model and a Navier-Stokes equation based
      incompressible flow model. Four vocal fold models, one with constant layer
      thickness and the others with different degrees of layer thickness variation in
      the longitudinal direction, were studied. It was found that the varied thickness
      resulted in up to 24% stiffness reduction at the middle and up to 47% stiffness
      increase near the anterior and posterior ends of the vocal fold; however, the
      average stiffness was not affected. The fluid-structure interaction simulations
      on the four models showed that the thickness variation did not affect vibration
      amplitude, glottal flow rate, and the waveform related parameters. However, it
      increased glottal angles at the middle of the vocal fold, suggesting that vocal
      fold vibration amplitude was determined by the average stiffness of the vocal
      fold, while the glottal angle was determined by the local stiffness. The models
      with longitudinal variation of layer thickness consumed less energy during the
      vibrations compared with the constant layer thickness one.

PMID- 30098146
TI  - Technique for Nonsurgical Lifting Procedures Using Polydioxanone Threads.

PMID- 30098147
TI  - A Poorly Differentiated Lung Malignancy in a Young Adult.

PMID- 30098148
TI  - A laboratory study on effects of cycling helmet fit on biomechanical measures
      associated with head and neck injury and dynamic helmet retention.
AB  - There is a scant biomechanical literature that tests, in a laboratory setting,
      whether or not determinants of helmet fit affect biomechanical parameters
      associated with injury. Using conventional cycling helmets and repeatable models
      of the human head and neck, integrated into a guided drop impact experiment at
      speeds up to 6m/s, this study tests the hypothesis that fit affects head
      kinematics, neck kinetics, and the extent to which the helmet moves relative to
      the underlying head (an indicator of helmet positional stability). While there
      were a small subset of cases where head kinematics were statistically
      significantly altered by fit, when viewed as a whole our measures of head
      kinematics suggest that fit does not systematically alter kinematics of the head
      secondary to impact. Similarly, when viewed as a whole our data suggests that fit
      does not systematically alter resultant neck compression and resultant moment and
      associated biomechanical measures. Our data suggests that backward fit helmets
      exhibit the worst dynamic stability, in particular when the torso is impacted
      before the helmeted head is impacted, suggesting that the typical certification
      method of dynamical loading of a helmet to quantify retention may not be
      representative of highly plausible cycling incident scenarios where impact forces
      are first applied to the torso leading to loading of the neck prior to the head.
      Further study is warranted so that factors of fit that affect injury outcome are
      uncovered in both laboratory and real world settings.

PMID- 30098149
TI  - Acute Vision Loss From Dacryocystitis.

PMID- 30098150
TI  - Assessment of the Accuracy of Disease Coding Among Patients Diagnosed With
      Sarcoma.

PMID- 30098151
TI  - Utility of Optical Coherence Tomography for Guiding Laser Therapy Among Patients
      With Recurrent Respiratory Papillomatosis.
AB  - Importance: Recurrent respiratory papillomatosis (RRP) is a viral-induced disease
      caused by human papillomavirus and the second leading cause of dysphonia in
      children; however, neither a cure nor a definitive surgical treatment is
      currently available for RRP. Although laser therapy is often used in the
      treatment of RRP, the lack of real-time laser-tissue interaction feedback
      undermines the ability of physicians to provide treatments with low morbidity.
      Therefore, an intraoperative tool to monitor and control laser treatment depth is
      needed. Objective: To investigate the potential of combining optical coherence
      tomography (OCT) with laser therapy for patient-tailored laryngeal RRP
      treatments. Design, Setting, and Participants: This in vivo study was performed
      at the Massachusetts Eye and Ear Infirmary from February 1, 2017, to September 1,
      2017. Three-dimensional OCT images were acquired before, during, and after
      photoangiolytic laser therapy in 10 pediatric patients with a history of
      papilloma growth who presented with lesions and hoarseness. Main Outcomes and
      Measures: Whether intraoperative OCT monitoring of changes in optical scattering
      and absorption provides quantitative information to control thermal damage in
      tissue. Results: Among the 10 pediatric patients (age range, 4-11 years; 6 male)
      included in the study, high-resolution OCT images revealed epithelial hyperplasia
      with clear RRP lesion margins. Images acquired during therapy indicated
      coagulation deep in tissue, and posttherapy images showed the ability to quantify
      the amount of tissue ablated by the photoangiolytic laser. Conclusions and
      Relevance: Concurrent use of OCT imaging and laser therapy may improve
      postoperative outcomes for patients with RRP by delivering an optimal, patient
      tailored treatment. Additional studies investigating the correlation between
      optical properties with vocal outcomes are required.

PMID- 30098152
TI  - Effect of Anlotinib as a Third-Line or Further Treatment on Overall Survival of
      Patients With Advanced Non-Small Cell Lung Cancer: The ALTER 0303 Phase 3
      Randomized Clinical Trial.
AB  - Importance: Anlotinib is a novel multitarget tyrosine kinase inhibitor for tumor
      angiogenesis and proliferative signaling. A phase 2 trial showed anlotinib to
      improve progression-free survival with a potential benefit of overall survival,
      leading to the phase 3 trial to confirm the drug's efficacy in advanced non-small
      cell lung cancer (NSCLC). Objective: To investigate the efficacy of anlotinib on
      overall survival of patients with advanced NSCLC progressing after second-line or
      further treatment. Design, Setting, and Participants: The ALTER 0303 trial was a
      multicenter, double-blind, phase 3 randomized clinical trial designed to evaluate
      the efficacy and safety of anlotinib in patients with advanced NSCLC. Patients
      from 31 grade-A tertiary hospitals in China were enrolled between March 1, 2015,
      and August 31, 2016. Those aged 18 to 75 years who had histologically or
      cytologically confirmed NSCLC were eligible (n = 606), and those who had
      centrally located squamous cell carcinoma with cavitary features or brain
      metastases that were uncontrolled or controlled for less than 2 months were
      excluded. Patients (n = 440) were randomly assigned in a 2-to-1 ratio to receive
      either 12 mg/d of anlotinib or a matched placebo. All cases were treated with
      study drugs at least once in accordance with the intention-to-treat principle.
      Main Outcomes and Measures: The primary end point was overall survival. The
      secondary end points were progression-free survival, objective response rate,
      disease control rate, quality of life, and safety. Results: In total, 439
      patients were randomized, 296 to the anlotinib group (106 [36.1%] were female and
      188 [64.0%] were male, with a mean [SD] age of 57.9 [9.1] years) and 143 to the
      placebo group (46 [32.2%] were female and 97 [67.8%] were male, with a mean [SD]
      age of 56.8 [9.1] years). Overall survival was significantly longer in the
      anlotinib group (median, 9.6 months; 95% CI, 8.2-10.6) than the placebo group
      (median, 6.3 months; 95% CI, 5.0-8.1), with a hazard ratio (HR) of 0.68 (95% CI,
      0.54-0.87; P = .002). A substantial increase in progression-free survival was
      noted in the anlotinib group compared with the placebo group (median, 5.4 months
      [95% CI, 4.4-5.6] vs 1.4 months [95% CI, 1.1-1.5]; HR, 0.25 [95% CI, 0.19-0.31];
      P < .001). Considerable improvement in objective response rate and disease
      control rate was observed in the anlotinib group over the placebo group. The most
      common grade 3 or higher adverse events in the anlotinib arm were hypertension
      and hyponatremia. Conclusions and Relevance: Among the Chinese patients in this
      trial, anlotinib appears to lead to prolonged overall survival and progression
      free survival. This finding suggests that anlotinib is well tolerated and is a
      potential third-line or further therapy for patients with advanced NSCLC. Trial
      Registration: ClinicalTrials.gov identifier: NCT02388919.

PMID- 30098154
TI  - Meta-analysis to Evaluate High-Dose Therapy Followed by Stem Cell Transplant in
      Patients With Multiple Myeloma-Reply.

PMID- 30098153
TI  - Calibration error due to different motion-encoding gradient strength on two
      scanners.
AB  - In this study, displacements of brain tissue in six human subjects and one
      gelatin "phantom" were measured by MR elastography on two MR scanners. Both were
      Siemens Trio 3T MRI scanners. One Trio scanner was located at the Beckman
      Institute at University of Illinois in Urbana-Champaign (UIUC; 4 subjects) and
      the other Trio scanner was at the Center for Clinical Imaging Research at
      Washington University in St. Louis (WU; 2 subjects and gel phantom). After
      publication, we discovered that the default motion-encoding gradient strength was
      not identical on the two scanners, but was lower on the WU scanner than on the
      UIUC scanner (20 mT/m vs 26 mT/m on the UIUC scanner). Thus in two subjects and
      the gel phantom, the estimated displacement amplitudes should be higher by a
      factor equal to 26/20 (1.3). Correcting this error changes estimates of mean and
      standard deviation of brain displacement, curl and strain values in the human
      brain by about 10% (due to 30% error in 2/6 subjects). Corresponding measurements
      in a gel phantom are also affected; these were included solely for qualitative
      comparison to the behavior of the brain. No statistical comparisons were affected
      by these errors. The main conclusions of the study are unchanged.

PMID- 30098155
TI  - Correction of a Graph's Axis Label.

PMID- 30098156
TI  - Finite Element Formulation of Multiphasic Shell Elements for Cell Mechanics
      Analyses in FEBio.
AB  - With the recent implementation of multiphasic materials in the open-source finite
      element (FE) software FEBio (febio.org), 3D models of cells embedded within the
      tissue may now be analyzed, accounting for porous solid matrix deformation,
      transport of interstitial fluid and solutes, membrane potential, and reactions.
      The cell membrane is a critical component in cell models, which selectively
      regulates the transport of fluid and solutes in the presence of large
      concentration and electric potential gradients, while also facilitating the
      transport of various proteins. The cell membrane is much thinner than the cell;
      therefore, in an FE environment, shell elements formulated as 2D surfaces in 3D
      space would be preferred for modeling the cell membrane, for the convenience of
      mesh generation from image-based data, especially for convoluted membranes.
      However, multiphasic shell elements are yet to be developed in the FE literature
      and commercial FE software. This study presents a novel formulation of
      multiphasic shell elements and its implementation in FEBio. The shell model
      includes front- and back-face nodal degrees of freedom for the solid
      displacement, effective fluid pressure and effective solute concentrations, and a
      linear interpolation of these variables across the shell thickness. This
      formulation was verified against classical models of cell physiology and
      validated against reported experimental measurements in chondrocytes. This
      implementation of passive transport of fluid and solutes across multiphasic
      membranes makes it possible to model the biomechanics of isolated cells or cells
      embedded in their extracellular matrix, accounting for solvent and solute
      transport.

PMID- 30098157
TI  - Determining subject-specific lower-limb muscle architecture data for
      musculoskeletal models using diffusion tensor MRI.
AB  - Accurate individualized muscle architecture data is crucial for generating
      subject-specific musculoskeletal models to investigate movement and dynamic
      muscle function. Diffusion tensor magnetic resonance (MR) imaging (DTI) has
      emerged as a promising method of gathering muscle architecture data in vivo,
      however its accuracy in estimating parameters such as muscle fiber lengths for
      creating subject-specific musculoskeletal models has not been tested. Here we
      provide a validation of the method of using anatomical MRI and DTI to gather
      muscle architecture data in vivo, by directly comparing those data obtained from
      MR scans of 3 human cadaveric lower limbs to those from dissections. DTI was used
      to measure fiber lengths and pennation angles, while the anatomical images were
      used to estimate muscle mass, which were used to calculate physiological cross
      sectional area (PCSA). The same data were then obtained through dissections,
      where it was found that on average muscle masses and fiber lengths matched well
      between the two methods (4% and 1% differences respectively), while PCSA values
      had slightly larger differences (6%). Overall, these results suggest that DTI is
      a promising technique to gather in vivo muscle architecture data, but further
      refinement and complementary imaging techniques may be needed to realize these
      goals.

PMID- 30098158
TI  - On Stability of Specific Adhesion of Particles to Membranes in Simple Shear Flow.
AB  - Adhesion of carrier particles to the luminal surface of endothelium under
      hemodynamic flow conditions is critical for successful vascular drug delivery.
      Endothelial cells line the inner surface of blood vessels. The effect of
      mechanical behavior of this compliant surface on the adhesion of blood-borne
      particles is unknown. In this contribution, we use a phase-plane method, first
      developed by Hammer and Lauffenburger [Biophysical Journal, 52, 475 (1987)], to
      analyze the stability of specific adhesion of a spherical particle to a compliant
      interface layer. We construct a phase diagram that predicts the state of particle
      adhesion, subjected to an incident simple shear flow, in terms of interfacial
      elasticity, shear rate, binding affinity of cell adhesive molecules, and their
      surface density. The main conclusion is that the local deformation of the
      flexible interface inhibits the stable adhesion of the particle. In comparison
      with adhesion to a rigid substrate, a greater ligand density is required to
      establish a stable adhesion between a particle and a compliant interface. The
      results can be used for the rational design of particles in vascular drug
      delivery.

PMID- 30098159
TI  - Meta-analysis to Evaluate High-Dose Therapy Followed by Stem Cell Transplant in
      Patients With Multiple Myeloma.

PMID- 30098160
TI  - Aortic expansion induces lumen narrrowing in anomalous coronary arteries: a
      parametric structural finite element analysis.
AB  - Anomalous aortic origin of coronary arteries (AAOCA) is a congenital disease that
      can lead to cardiac ischemia during intense physical activity. Although AAOCA is
      responsible for sudden cardiac death (SCD) among young athletes and soldiers, the
      mechanisms underlying the coronary occlusion during physical effort still have to
      be clarified. The present study investigates the correlation between geometric
      features of the anomaly and coronary lumen narrowing under aortic root
      dilatations. Idealized parametric computer-aided designed (CAD) models of the
      aortic root with anomalous and normal coronary are created and static finite
      element (FE) simulations of increasing aortic root expansions are carried out.
      Different coronary take-off angles and intramural penetrations are investigated
      to assess their role on coronary lumen narrowing. Results show that increasing
      aortic and coronary pressures lead to lumen expansions in normal coronaries,
      particularly in the proximal tract, while the expansion of anomalous coronary is
      impaired especially at the ostium. Concerning the geometric features of the
      anomaly, acute take-off angles cause elongated coronary ostia, with an
      eccentricity increasing with aortic expansion; the impact of intramural
      penetration of coronary on its luminal narrowing is limited. The present study
      provides a proof of concept of the biomechanical reasons underlying the lumen
      narrowing in AAOCA during aortic expansion, promoting the role of computational
      simulations as a tool to assess the mechanisms of this pathology.

PMID- 30098162
TI  - Association of Fellow Eye With Study Eye Disease Trajectories and Need for Fellow
      Eye Treatment in Collaborative Initial Glaucoma Treatment Study (CIGTS)
      Participants.
AB  - Importance: Clinicians would benefit from knowing the association of glaucomatous
      change in 2 eyes of the same patient. Objective: To estimate the time between
      initial glaucoma treatment of the study eye (SE) and the need for treatment of
      the fellow eye (FE) and to ascertain the concordance between rates of progression
      in SEs and FEs. Design, Setting, and Participants: In this post hoc analysis of
      participants from the Collaborative Initial Glaucoma Treatment Study, 607
      participants with newly diagnosed open-angle glaucoma in 1 or both eyes were
      followed up for up to 11 years. An SE was designated at baseline and randomized
      to medical or surgical treatment. By protocol, FEs were treated when eligible or
      at physician discretion. Survival analysis methods were used to estimate the
      probability of FE treatment over time and to test baseline and time-dependent
      predictors of treatment. Disease trajectory was calculated with linear regression
      as the patient eye-specific slopes of mean deviation (MD) and intraocular
      pressure (IOP) over time, and correlations between SE and FE trajectories were
      calculated. Data were collected from October 1993 to December 2004. Data were
      analyzed from September 2012 to May 2018. Main Outcomes and Measures: Time to FE
      treatment and slopes over time of MD and IOP in SEs and FEs. Results: Of the 607
      included patients, 334 (55.0%) were male and 337 (55.5%) were white, and the mean
      (SD) age was 58.0 (10.9) years. A total of 291 FEs (47.9%) were treated at
      baseline, 123 (20.3%) were eventually treated, and 193 (31.8%) never received
      treatment. The probability of FE treatment for open-angle glaucoma was 0.57 at 1
      year and 0.68 at 7 years after randomization. Characteristics significantly
      associated with an increased hazard of FE treatment included older age (hazard
      ratio [HR], 1.33; 95% CI, 1.08-1.64; P = .007), hypertension (HR, 1.76; 95% CI,
      1.16-2.67; P = .008), higher IOP (HR, 1.24; 95% CI, 1.20-1.29; P < .001), large
      cup-disc ratio (HR, 1.40; 95% CI, 1.23-1.58; P < .001), and worse MD.
      Correlations in MD slopes between SEs and FEs initially, eventually, and never
      treated were 0.73, 0.71, and 0.34, respectively. Comparable correlations in IOP
      slopes were 0.57, 0.24, and 0, respectively. Conclusions and Relevance: Among
      patients with newly diagnosed open-angle glaucoma, almost half had initial
      treatment of both eyes. After 7 years, approximately two-thirds of patients had
      bilateral treatment. Of the variables predictive of FE treatment, modifiable
      factors included hypertension and IOP. Slopes of MD were similar between SEs and
      treated FEs. This implies that SE change is a harbinger of FE change and
      therefore warrants close surveillance.

PMID- 30098161
TI  - Preoperative Tranexamic Acid for Treatment of Bleeding, Edema, and Ecchymosis in
      Patients Undergoing Rhinoplasty: A Systematic Review and Meta-analysis.
AB  - Importance: Evidence has emerged on the efficacy of tranexamic acid to control
      blood loss and postoperative complications after rhinoplasty. Objective: To
      investigate the results of tranexamic acid use to reduce intraoperative bleeding,
      postoperative eyelid edema, and periorbital ecchymosis in rhinoplasty. Data
      Sources and Study Selection: For this systematic review of randomized clinical
      trials, searches were performed in PubMed, Cochrane Central Register of
      Controlled Trials, Web of Science, SCOPUS, Science Direct, Google Scholar,
      OpenThesis, and ClinicalTrials.gov from inception to December 23, 2017. Key words
      included tranexamic acid, rhinoplasty, and nasal surgical procedures. The
      following elements were used to define eligibility criteria: (1) population:
      patients undergoing rhinoplasty surgery; (2) intervention and controls:
      tranexamic acid vs placebo solution or no-treatment control group; (3) outcomes:
      intraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis,
      and thromboembolic events; and (4) study type: randomized clinical trials. Data
      Extraction and Synthesis: Two reviewers extracted data and assessed study quality
      according to the Cochrane guidelines for randomized clinical trials. Treatment
      effects were defined as weighted mean difference (WMD) and 95% CIs. The strength
      of evidence was analyzed using the Grading of Recommendations Assessment,
      Development, and Evaluation rating system. Main Outcomes and Measures:
      Intraoperative bleeding, postoperative eyelid edema and periorbital ecchymosis.
      To calculate the effect sizes, means and SDs were obtained for each study group
      and outcome of interest. Results: Five studies comprising 276 patients were
      included in the systematic review: 177 patients (64.1%) were women, and mean age
      was 26.8 (range, 16-42) years. Four studies comprising 246 patients estimated the
      amount in intraoperative bleeding as a primary outcome and were included in the
      meta-analysis. Eyelid edema and ecchymosis were evaluated as outcomes in 2
      studies. Tranexamic acid was associated with reduced bleeding during rhinoplasty
      was found (WMD, -42.28 mL; 95% CI, -70.36 to -14.21 mL), with differences (P =
      .01) between oral (WMD, -61.70 mL; 95% CI, -83.02 to -40.39 mL; I2 = 0%) and
      intravenous (WMD, -23.88 mL; 95% CI, -45.19 to -2.58 mL; I2 = 56%)
      administration. Eyelid edema and ecchymosis scores in patients receiving
      tranexamic acid were significantly lower compared with the control group within
      the first postoperative week: lower eyelid edema, WMD, -0.76; 95% CI, -1.04 to 
      0.49 and lower eyelid ecchymosis, WMD, -0.94; 95% CI, -1.80 to -0.08. No cases of
      thromboembolic events were reported. Conclusions and Relevance: Current available
      evidence suggests that preoperative administration of tranexamic acid is safe and
      may reduce intraoperative bleeding as well as postoperative eyelid edema and
      ecchymosis in patients undergoing rhinoplasty.

PMID- 30098163
TI  - Association of MUC16 Mutation With Tumor Mutation Load and Outcomes in Patients
      With Gastric Cancer.
AB  - Importance: MUC16, which encodes cancer antigen 125 (CA-125), is frequently
      mutated in gastric cancer (GC); however, its association with tumor mutation load
      (TML) and outcome in patients with GC has not been established, to date.
      Objective: To investigate whether MUC16 mutations are associated with TML and
      prognosis in patients with GC. Design, Setting, and Participants: Statistical
      analysis of genomic data from 437 GC samples obtained from The Cancer Genome
      Atlas (TCGA) and 256 samples from an Asian cohort. Both cohorts contained data of
      patients with GC involved in previous genomic studies. Data were obtained from
      TCGA on September 3, 2017, and from the Asian cohort on March 5, 2013, and
      analyzed from September 3 to December 1, 2017. The TCGA cohort was used as a
      discovery set and the Asian cohort as a validation set. Kaplan-Meier survival
      analysis and multivariate Cox and logistic regression models were applied.
      Regression models addressed confounding factors; Bayesian variant nonnegative
      matrix factorization was used to extract mutational signatures. The MutSigCV
      algorithm was used to identify significantly mutated genes. Main Outcomes and
      Measures: Primary outcomes were mutation frequency, overall survival, and TML,
      calculated using Kaplan-Meier survival analysis, odds ratios (ORs), and
      significance of signaling pathways. Results: MUC16 was mutated in 168 of 437
      (38.4%) of the GC samples from the TCGA cohort and in 57 of 256 (22.3%) from the
      Asian cohort. In both cohorts, GC samples with MUC16 mutations exhibited
      significantly greater TML than those without MUC16 mutations (median mutation
      counts: TCGA cohort, 264 with MUC16 mutation vs 115 without; Asian cohort, 134
      with MUC16 mutation vs 74 without; Wilcoxon rank sum test, both P < .001). This
      association was independent of mutations in POLE and BRCA1/2 and mutational
      signatures in the TCGA cohort (OR, 1.87; 95% CI, 1.49-2.36; P < .001) and the
      Asian cohort (OR, 1.69; 95% CI, 1.25-2.29; P < .001). MUC16 mutations were
      significantly associated with better prognosis in both cohorts (median overall
      survival, 46.9 [95% CI, 26.4-NA (not available)] vs 26.7 [95% CI, 20.2-43.1]
      months; log-rank test, P = .007 [TCGA cohort] and not calculable [the median
      overall survival of patients with GC and MUC16 mutations could not be calculated
      because more than half the patients in the group were alive] vs 36.8 months; P =
      .04 [Asian cohort]). The association remained statistically significant after
      controlling for age, sex, TNM stage, mutations in POLE and BRCA1/2, and
      mutational signatures (hazard ratio, 0.61 [95% CI, 0.42-0.89]; log rank test, P =
      .01). Immune response and cell cycle regulation circuits were among the top
      altered signaling pathways in samples with MUC16 mutations (normalized enrichment
      score, 1.70 [95% CI, 1.57-1.79] and 2.04 [95% CI, 1.90-2.18]; adjusted P < .001).
      The prognostic significance of MUC16 mutation identified in the TCGA cohort was
      validated in the Asian cohort. Conclusions and Relevance: These findings indicate
      that MUC16 mutations may be associated with higher TML, better survival outcomes,
      and immune response and cell cycle pathways. These findings may be immediately
      applicable for guiding immunotherapy treatment for patients with GC.

PMID- 30098164
TI  - Assessment of Pliability and Elasticity of the External Nasal Skin in Patients
      With Unilateral Nasal Valve Collapse: A Static Biomechanical Evaluation.
AB  - Importance: Understanding the skin biomechanics, specifically pliability and
      elasticity, in patients with nasal valve collapse may allow for new methods to
      assess which patients require more advanced nasal valve surgery. Objective: To
      test the hypothesis that in patients with unilateral nasal valve collapse, the
      side of the nose with the collapse will have lower elasticity and increased
      pliability compared with the normal side, as assessed by a blinded observer using
      the Cutometer MPA 580. Design, Setting, and Participants: Prospective,
      investigator-blinded, case-control cohort study of patients with unilateral nasal
      valve collapse and subjective nasal obstruction conducted in an academic
      otolaryngology-head and neck surgery clinic. Interventions: Patients were
      assessed using the Cutometer MPA 580 by a blinded assessor. Three measurements
      were performed bilaterally on the exterior skin of the nose corresponding to the
      level of the inferior edge of the upper lateral cartilage. Measurements taken at
      the skin inferior to the zygoma were used as a control. Main Outcomes and
      Measures: Primary outcome measures of the nasal skin were pliability (Uf, defined
      as the lengthening of the skin after 3 seconds of constant load) and elasticity
      (Ua/Uf, defined as the percentage of the skin that returned to its normal
      position 3 seconds after the release from the 3-second constant load). Results:
      Of the 27 patients included in the study, 15 (56%) were male, and 12 (44%) were
      female; mean (SD) age, 44 (21) years (range, 16-90 years). There was no
      difference between the measurements of the skin overlying the area of nasal valve
      collapse in elasticity: side without collapse (0.960% [0.031%]) vs side with
      collapse (0.967% [0.036%]) (mean difference, 0.007%; 95% CI, -0.018% to 0.021%)
      (P = .90). However, there was a significant difference in pliability: side of the
      nose without collapse (0.520 [0.139] mm) vs side with collapse (0.610 [0.200])
      (mean difference, 0.090 mm; 95% CI, 0.014-0.156 mm) (P = .02). Conclusions and
      Relevance: Although the skin in patients with nasal valve collapse appears to
      maintain its elasticity, it demonstrates an increased ability to stretch and
      lengthen compared with nasal skin of those without valve collapse. Future studies
      are required to determine whether the biomechanical changes are related to the
      length and severity of nasal obstruction, or whether these changes in the skin
      may help predict who will benefit from nasal valve surgery and whether these
      patients are at an increased risk of surgical failure. Level of Evidence: 2.

PMID- 30098166
TI  - Optimizing Cancer Treatment Using Game Theory: A Review.
AB  - Importance: While systemic therapy for disseminated cancer is often initially
      successful, malignant cells, using diverse adaptive strategies encoded in the
      human genome, almost invariably evolve resistance, leading to treatment failure.
      Thus, the Darwinian dynamics of resistance are formidable barriers to all forms
      of systemic cancer treatment but rarely integrated into clinical trial design or
      included within precision oncology initiatives. Observations: We investigate
      cancer treatment as a game theoretic contest between the physician's therapy and
      the cancer cells' resistance strategies. This game has 2 critical asymmetries:
      (1) Only the physician can play rationally. Cancer cells, like all evolving
      organisms, can only adapt to current conditions; they can neither anticipate nor
      evolve adaptations for treatments that the physician has not yet applied. (2) It
      has a distinctive leader-follower (or "Stackelberg") dynamics; the "leader"
      oncologist plays first and the "follower" cancer cells then respond and adapt to
      therapy. Current treatment protocols for metastatic cancer typically exploit
      neither asymmetry. By repeatedly administering the same drug(s) until disease
      progression, the physician "plays" a fixed strategy even as the opposing cancer
      cells continuously evolve successful adaptive responses. Furthermore, by changing
      treatment only when the tumor progresses, the physician cedes leadership to the
      cancer cells and treatment failure becomes nearly inevitable. Without fundamental
      changes in strategy, standard-of-care cancer therapy typically results in "Nash
      solutions" in which no unilateral change in treatment can favorably alter the
      outcome. Conclusions and Relevance: Physicians can exploit the advantages
      inherent in the asymmetries of the cancer treatment game, and likely improve
      outcomes, by adopting more dynamic treatment protocols that integrate eco
      evolutionary dynamics and modulate therapy accordingly. Implementing this
      approach will require new metrics of tumor response that incorporate both
      ecological (ie, size) and evolutionary (ie, molecular mechanisms of resistance
      and relative size of resistant population) changes.

PMID- 30098167
TI  - Association of Corticosteroid Use With Incidence of Central Serous
      Chorioretinopathy in South Korea.
AB  - Importance: Information on the incidence of central serous chorioretinopathy
      (CSC) in individuals who receive corticosteroids is scarce but clinically
      important because these agents are useful and widely used. Objective: To estimate
      the annual and 5-year incidence of CSC in South Korea in the overall population
      and in those who have used corticosteroid medications. Design, Setting, and
      Participants: A cohort study of a population-based random sample included East
      Asian adults for whom records are held in the Korean National Health Insurance
      Service database for calendar years 2011 through 2015. The data analysis was
      performed from July 1, 2017 to January 5, 2018. Exposures: Any type of
      corticosteroid use from 2002 through 2015. Main Outcomes and Measures: Incidence
      of CSC. Results: The data set contained data from 868 939 adults (4 117 768
      person-years). From 2011 through 2015, 1423 individuals (among whom the mean [SD]
      age was 46.8 [16.4] years and 1091 [76.7%] were male) with newly diagnosed CSC
      were identified. From 2002 to 2015, 783 099 individuals in the data set (90.1%)
      had ever used corticosteroids. The incidence of CSC per 10 000 person-years was
      3.5 (5.4 in men; 1.6 in women) among the total population, 2.5 (3.0 in men; 1.2
      in women) in those who had never used corticosteroids, and 3.6 (5.7 in men; 1.6
      in women) among those who had ever used corticosteroids. The risk of CSCR with
      individuals who had ever used corticosteroids was estimated as an adjusted hazard
      ratio of 1.81 (95% CI, 1.47-2.23) compared with those who have never used these
      drugs. Current or recent corticosteroid use showed a positive association with
      the incidence of CSC (depending on duration of use, adjusted hazard ratio ranged
      from 1.54 to 2.15). Corticosteroid use in 2006 through 2009 was associated with
      an increased incidence of CSC after 2011 (adjusted hazard ratio 1.57 [95% CI,
      1.13-2.18]). Conclusions and Relevance: In 2002 through 2015, 90.1% of adults in
      Korea received corticosteroids at least once. Although there was a clear
      difference in relative risk, this data analysis could not replicate the more than
      30-fold increase in the risk ratio of CSC that has been reported previously. The
      incidence of CSC in the most vulnerable group, middle-aged men, was estimated to
      be approximately 1 case per 1000 corticosteroid users in the year following
      medication use. The overall incidence among those who had ever used
      corticosteroids and those who had never used these drugs was 2.5 and 3.6 per 10
      000 person-years, respectively. This study provides additional evidence to
      support the potential role of corticosteroids in CSC.

PMID- 30098168
TI  - Clinical Practice Guidelines: What's Next?

PMID- 30098165
TI  - Maintenance Treatment and Survival in Patients With Myeloma: A Systematic Review
      and Network Meta-analysis.
AB  - Importance: Several trials demonstrated the impact of novel agent-based
      maintenance in newly diagnosed multiple myeloma (NDMM), but there is no current
      evidence demonstrating the superiority of one regimen over the other, owing to
      the lack of direct/indirect comparisons. Objective: To analyze and compare the
      effectiveness of different maintenance regimens in NDMM via a network meta
      analysis. Data Sources: We performed 2 independent searches in PubMed and
      Cochrane databases, and then we identified all the records registered after 1999
      and on or before November 20, 2017. Study Selection: By blinded review, we
      identified prospective phase 3 randomized trials evaluating novel agent-based
      maintenance in patients with NDMM; the included studies compared at least 2
      maintenance approaches; comparators included placebo and no maintenance. From 364
      screened records, 11 studies were included. Data Extraction and Synthesis: We
      followed (independent extraction) the guidelines provided by the PRISMA Report
      and the EQUATOR Network. The evidence was synthesized using a network meta
      analysis (NMA). To allow comparison of all treatments, no maintenance was
      selected as common comparator and the effect of placebo was assumed to be the
      same as no treatment. The best option was identified by a Bayesian consistency
      model based on hazard ratio (HR), 95% credible interval (CrI), probability of
      being the best treatment (PbBT), and median ranking distribution (MedR). Main
      Outcomes and Measures: Outcomes of interest were progression-free survival (PFS)
      and overall survival (OS). Results: Eleven trials and 8 treatments including a
      total of 5073 participants were included. By PFS analysis, lenalidomide-based
      regimens (lenalidomide-prednisone, lenalidomide alone) were identified as the
      most effective options (HR, 0.39 [95% CrI, 0.28-0.53] and 0.47 [95% CrI, 0.39
      0.55], respectively; MedR, 1 and 2; overall PbBT, 74%). Four treatments
      (thalidomide-interferon, thalidomide-bortezomib, bortezomib-prednisone,
      thalidomide alone) showed an HR in favor of maintenance. By OS analysis,
      lenalidomide alone was identified as the best option (HR, 0.76; 95% CrI, 0.51
      1.16; MedR, 2; PbBT, 38%), followed by bortezomib-thalidomide and bortezomib
      prednisone. Similar features were noticed in the restricted network including
      transplant trials, in the sensitivity analysis, and in most of the prognostic
      subgroups. Conclusions and Relevance: Based on PFS and OS results of this NMA,
      lenalidomide maintenance appears to be the best treatment option, by synthesizing
      the available evidence of novel agent-based maintenance in the past 20 years.

PMID- 30098169
TI  - Quantitative Analysis of Agrammatism in Agrammatic Primary Progressive Aphasia
      and Dominant Apraxia of Speech.
AB  - Purpose: The aims of the study were to assess and compare grammatical deficits in
      written and spoken language production in subjects with agrammatic primary
      progressive aphasia (agPPA) and in subjects with agrammatism in the context of
      dominant apraxia of speech (DAOS) and to investigate neuroanatomical correlates.
      Method: Eight agPPA and 21 DAOS subjects performed the picture description task
      of the Western Aphasia Battery (WAB) both in writing and orally. Responses were
      transcribed and coded for linguistic analysis. agPPA and DAOS were compared to 13
      subjects with primary progressive apraxia of speech (PPAOS) who did not have
      agrammatism. Spearman correlations were performed between the written and spoken
      variables. Patterns of atrophy in each group were compared, and relationships
      between the different linguistic measures and integrity of Broca's area were
      assessed. Results: agPPA and DAOS both showed lower mean length of utterance,
      fewer grammatical utterances, more nonutterances, more syntactic and semantic
      errors, and fewer complex utterances than PPAOS in writing and speech, as well as
      fewer correct verbs and nouns in speech. Only verb ratio and proportion of
      grammatical utterances correlated between modalities. agPPA and DAOS both showed
      greater involvement of Broca's area than PPAOS, and atrophy of Broca's area
      correlated with proportion of grammatical and ungrammatical utterances and
      semantic errors in writing and speech. Conclusions: agPPA and DAOS subjects
      showed similar patterns of agrammatism, although subjects performed differently
      when speaking versus writing. Integrity of Broca's area correlates with
      agrammatism.

PMID- 30098170
TI  - Use of Palliative Care Earlier in the Disease Course in the Context of the Opioid
      Epidemic: Educational, Research, and Policy Issues.

PMID- 30098171
TI  - New Insights Into the Development and Progression of Geographic Atrophy After
      Full Thickness Autologous Choroidal Graft.
AB  - Purpose: To investigate if the contiguity between native and transplanted retinal
      pigment epithelium (RPE) represents a protective factor against the progression
      of atrophy after autologous choroidal graft. In addition, the changes in fundus
      autofluorescence (FAF) in the contiguous and noncontiguous RPE areas were
      explored. Methods: The first postoperative reliable FAF image was selected and
      divided into sectors based on the characteristics of the RPE at the edge of the
      graft. The sectors were categorized into three groups: contiguous RPE,
      noncontiguous RPE, and not classifiable. The area of RPE atrophy, inside and
      outside the graft, was measured for each sector at baseline, one, three, and five
      years of follow-up. The FAF pattern outside the graft was evaluated for every
      sector at baseline and during the follow-up. Results: Nineteen patients met the
      inclusion criteria and were included in this study. Trend analysis showed that
      the atrophy progression outside the graft was statistically significant in areas
      where native and transplanted RPE were noncontiguous (P < 0.0001) yet not so in
      contiguous areas (P < 0.058). Inside the graft, both groups showed an increase in
      atrophy over time. In addition, the noncontiguous group developed more severe
      increased FAF patterns compared with the contiguous group. Conclusions: RPE
      contiguity after autologous choroidal graft seems to be a protective factor
      against atrophy progression, whereas any area of damaged or absent RPE tends to
      enlarge over time. This may suggest that the transplantation of an RPE sheet is
      more likely to be effective than an RPE cell suspension.

PMID- 30098173
TI  - Differential Effects of Isoproterenol on Regional Myocardial Mechanics in Rat
      using 3D cine DENSE Cardiovascular Magnetic Resonance.
AB  - The present study assessed the acute effects of isoproterenol on left ventricular
      (LV) mechanics in healthy rats with the hypothesis that beta-adrenergic
      stimulation influences the mechanics of different myocardial regions of the LV
      wall in different ways. To accomplish this, magnetic resonance images were
      obtained in the LV of healthy rats with or without isoproterenol infusion. The LV
      contours were divided into basal, mid-ventricular, and apical regions.
      Additionally, the mid-ventricular myocardium was divided into three transmural
      layers with each layer partitioned into four segments (i.e., septal, inferior,
      lateral, and anterior). Peak systolic strains and torsion were quantified for
      each region. Isoproterenol significantly increased peak systolic radial strain
      and circumferential-longitudinal shear strain, as well as ventricular torsion,
      throughout the basal, mid-ventricle, and apical regions. In the mid-ventricle,
      isoproterenol significantly increased peak systolic radial strain, and induced
      significant increases in peak systolic circumferential strain and longitudinal
      strain in the septum. Isoproterenol consistently increased peak systolic
      circumferential-longitudinal shear strain in all mid-ventricular segments.
      Ventricular torsion was significantly increased in nearly all segments except the
      inferior sub-endocardium. The effects of isoproterenol on LV systolic mechanics
      (i.e., 3D strains and torsion) in healthy rats depend on the region. This region
      dependency is also strain component-specific. These results provide insight into
      the regional response of LV mechanics to beta-adrenergic stimulation in rats, and
      could act as a baseline for future studies on subclinical abnormalities
      associated with the inotropic response in heart disease.

PMID- 30098174
TI  - Low-spatial-frequency bias in context-dependent visual size perception.
AB  - Spatial frequency (SF) information is essential for visual perception. By
      combining a sensitization procedure and the Ebbinghaus illusion, we investigated
      the effect of SF bias in context-dependent visual size perception. During the
      sensitization phase, participants were repeatedly presented with low- or high
      pass filtered faces or gratings and were asked to discriminate the gender or the
      orientation of them, respectively. Immediately following the sensitization phase,
      the Ebbinghaus illusion strength was measured. The results showed that the
      illusion strength was significantly larger when the prior sensitized images were
      low-pass filtered relative to when they were high-pass filtered. Moreover, this
      SF bias was independent of low-level features and the specific content of the
      filtered images. Our findings extend the understanding of SF bias induced by
      sensitization in visual domain, and suggest that the processing of context
      dependent visual size information is likely to involve magnocellular projections
      from subcortical areas via low SF channel.

PMID- 30098175
TI  - Deformation-induced transparency resolves color scission.
AB  - Dynamic image deformation produces the perception of a transparent material that
      appears to deform the background image by light refraction. Since past studies on
      this phenomenon have mainly used subjective judgment about the presence of a
      transparent layer, it remains unsolved whether this is a real perceptual
      transparency effect in the sense that it forms surface representations, as do
      conventional transparency effects. Visual computation for color and luminance
      transparency, induced mainly by surface-contour information, can be decomposed
      into two components: surface formation to determine foreground and background
      layers, and scission to assign color and luminance to each layer. Here we show
      that deformation-induced perceptual transparency aids surface formation by color
      transparency and consequently resolves color scission. We asked observers to
      report the color of the front layer in a spatial region with a neutral physical
      color. The layer color could be seen as either reddish or greenish depending on
      the spatial context producing the color transparency, which was, however,
      ambiguous about the order of layers. We found that adding to the display a
      deformation-induced transparency that could specify the front layer significantly
      biased color scission in the predicted way if and only if the deformation-induced
      transparency was spatially coincident with the interpretation of color
      transparency. The results indicate that deformation-induced transparency is
      indeed a novel type of perceptual transparency that plays a role in surface
      formation in cooperation with color transparency.

PMID- 30098172
TI  - A Role for betaA3/A1-Crystallin in Type 2 EMT of RPE Cells Occurring in Dry Age
      Related Macular Degeneration.
AB  - Purpose: The RPE cells have a major role in the development of dry age-related
      macular degeneration (AMD). We present novel evidence that betaA3/A1-crystallin,
      encoded by the Cryba1 gene, a protein known to be important for lysosomal
      clearance in the RPE, also has a role in epithelial-to-mesenchymal transition
      (EMT) of RPE cells. Methods: RPE from dry AMD globes, genetically engineered mice
      lacking Cryba1 globally or specifically in the RPE, spontaneous mutant rats
      (Nuc1) with a loss-of-function mutation in Cryba1, and the melanoma OCM3 cell
      line were used. Spatial localization of proteins was demonstrated with
      immunofluorescence, gene expression levels were determined by quantitative PCR
      (qPCR), and protein levels by Western blotting. Cell movement was evaluated using
      wound healing and cell migration assays. Co-immunoprecipitation was used to
      identify binding partners of betaA3/A1-crystallin. Results: betaA3/A1-crystallin
      is upregulated in polarized RPE cells compared to undifferentiated cells. Loss of
      betaA3/A1-crystallin in murine and human RPE cells resulted in upregulation of
      Snail and vimentin, downregulation of E-cadherin, and increased cell migration.
      betaA3/A1-crystallin binds to cortactin, and loss of betaA3/A1-crystallin
      resulted in increased P-cortactinY421. The RPE from AMD samples had increased
      Snail and vimentin, and decreased E-cadherin, compared to age-matched controls.
      Conclusions: We introduced a novel concept of dry AMD initiation induced by
      lysosomal clearance defects in the RPE and subsequent attempts by RPE cells to
      avoid the resulting stress by undergoing EMT. We demonstrate that betaA3/A1
      crystallin is a potential therapeutic target for AMD through rejuvenation of
      lysosomal dysfunction and potentially, reversal of EMT.

PMID- 30098176
TI  - Symmetry perception for patterns defined by color and luminance.
AB  - Perception of visual symmetry is fast and efficient and relies on both early low
      level and late mid- and high-level neural mechanisms. To test for potential
      influences of early low-level mechanisms on symmetry perception, we used
      isoluminant, achromatic, and combined (color + luminance) patterns in a
      psychophysical and an event-related-potential (ERP) experiment. In the
      psychophysical experiment, pattern contrast was fixed at individual symmetry
      discrimination threshold. Participants then judged whether a pattern was
      symmetric or random. Stimuli at isoluminance were associated with a large bias
      toward symmetry, achromatic stimuli introduced the opposite bias, and stimuli
      containing a balance of both color and luminance were perceived without bias.
      These findings are in line with distinct contrast sensitivity functions for color
      and luminance, with color providing low-frequency information useful for symmetry
      detection and luminance providing high-frequency information useful for detection
      of detail. The subsequent ERP experiment was run at high contrasts to assess
      processing of symmetry in suprathreshold conditions. Sustained posterior
      negativity, a symmetry-sensitive ERP component, was observed in all conditions
      and showed the expected dependence on symmetry. However, interactions between
      symmetry and contrast type were not observed. In conclusion, while our findings
      at threshold support models that propose an important contribution of low-level
      mechanisms to symmetry perception, at suprathreshold these low-level
      contributions do not persist. Therefore, under everyday viewing conditions,
      symmetry perception engages a relatively broad cortical network that is not
      constrained by low-level inputs.

PMID- 30098177
TI  - Cognition modulates action-to-perception transfer in ambiguous perception.
AB  - Can cognition penetrate action-to-perception transfer? Participants observed a
      structure-from-motion cylinder of ambiguous rotation direction. Beforehand, they
      experienced one of two mechanical models: An unambiguous cylinder was connected
      to a rod by either a belt (cylinder and rod rotating in the same direction) or by
      gears (both rotating in opposite directions). During ambiguous cylinder
      presentation, mechanics and rod were invisible, making both conditions visually
      identical. Observers inferred the rod's direction from their moment-by-moment
      subjective perceptual interpretation of the ambiguous cylinder. They reported the
      (hidden) rod's direction by rotating a manipulandum in either the same or the
      opposite direction. With respect to their effect on perceptual stability, the
      resulting match/nonmatch between perceived cylinder rotation and manipulandum
      rotation showed a significant interaction with the cognitive model they had
      previously been biased with. For the "belt" model, congruency between cylinder
      perception and manual action is induced by same-direction report. Here, we found
      that same-direction movement stabilized the perceived motion direction,
      replicating a known congruency effect. For the "gear" model, congruency between
      perception and action is-in contrast-induced by opposite-direction report. Here,
      no effect of perception-action congruency was found: Perceptual congruency and
      cognitive model nullified each other. Hence, an observer's internal model of a
      machine's operation guides action-to-perception transfer.

PMID- 30098178
TI  - Test-retest reliability of non-linear methods to assess walking dynamics.
AB  - The present study investigated the day-to-day reliability (quantified by the
      absolute and relative reliability) of nonlinear methods that assess human
      locomotion dynamics. Twenty-four participants completed 5 minutes of treadmill
      walking at self-selected preferred speed on two separate days. Lower limb
      kinematics were recorded at 100Hz and hip, knee and ankle joint angles, three
      dimensional sacrum marker displacement and stride time intervals were extracted
      for 170 consecutive strides. The largest Lyapunov exponent and correlation
      dimension were calculated for the joint angle and sacrum displacement data using
      three different state space reconstruction methods (group average, test-retest
      average, individual time delay and embedding dimension). Sample entropy and
      detrended fluctuation analysis were applied to the stride time interval time
      series. Relative reliability was assessed using intra-class correlation
      coefficients and absolute reliability was determined by measurement error (ME).
      The group average state space reconstruction method resulted in the best relative
      and absolute reliability of the LyE parameter when compared to the individual and
      test-retest average methods. The detrended fluctuation analysis exhibited good
      reliability, while sample entropy showed poor reliability. The results comprise a
      reference material that can inspire and guide future studies of non-linear gait
      dynamics.

PMID- 30098181
TI  - Swept-Source Optical Coherence Tomography Angiography of Microaneurysms in Myopic
      Retinoschisis.

PMID- 30098183
TI  - Visualization of Capillary Dropout Emanating From an Optic Disc Pit Using Optical
      Coherence Tomography Angiography.

PMID- 30098182
TI  - Punctate Retinal Pigment Epitheliopathy and Choroidopathy After Radiotherapy With
      Chemotherapy.

PMID- 30098184
TI  - Extensive Intraocular Osseous Metaplasia With Bone Marrow Formation.

PMID- 30098188
TI  - Modeling the Origin of the Ocular Pulse and Its Impact on the Optic Nerve Head.
AB  - Purpose: To use finite element (FE) analysis to understand the origin of the
      ocular pulse and predict its biomechanical impact on the optic nerve head (ONH).
      Methods: An FE model of a healthy eye was reconstructed. The choroid was biphasic
      and consisted of a solid phase (connective tissues) and a fluid phase (blood). We
      applied arterial blood pressure at 18 entry sites (posterior ciliary arteries)
      and venous blood pressure at 4 exit sites (vortex veins). For one cardiac cycle,
      we reported the resulting pulse volume, the ocular pulse amplitude (OPA), and
      diastole-to-systole ONH deformations. We also studied the effect of a change in
      scleral stiffness, in arterial pressure, and in baseline IOP. Results: During the
      cardiac cycle, a change in arterial pressure resulted in choroidal expansion,
      which in turn induced a change in IOP (the OPA) and ONH deformations. From
      diastole to systole, we found that choroidal expansion made the peripapillary
      retina move anteriorly, but both choroidal expansion and the OPA made the
      prelamina and LC move posteriorly. The net result was shearing of neural tissues
      in the neuroretinal rim. Both a stiffer sclera and a higher IOP resulted in a
      higher OPA, smaller pulse volume, larger diastole-to-systole ONH strains, and
      neural tissue shear in the neuroretinal rim. Increasing the arterial pressure had
      the same effect, except that it increased the pulse volume. Conclusions: Our
      models indicate that, during the cardiac cycle, the OPA and choroidal expansion
      can deform the ONH with a net shearing of neural tissues within the neuroretinal
      rim.

PMID- 30098189
TI  - Eye Tracking Results in Postconcussive Syndrome Versus Normative Participants.
AB  - Purpose: Standard physical, neurologic, and neuropsychologic examinations may not
      detect abnormalities after mild traumatic brain injury (mTBI). An analysis of eye
      movements may be more sensitive to neurologic dysfunction. Methods: We performed
      eye tracking assessments in 71 active duty and veteran military personnel with
      persistent postconcussive symptoms (3 months to 5 years after mTBI) and 75
      volunteers with no history of brain injury. Both eyes were sampled at 500 Hz and
      analyzed for various eye measurement parameters during visual tasks involving the
      saccadic and smooth systems. Results: No difference between mTBI and normal
      participants in main sequence profiles was observed. On the circular task,
      intersaccadic interval duration was shorter in mTBI compared with normal subjects
      (horizontal: Cohen's D = -0.65; vertical: Cohen's D = -0.75). For reading,
      absolute saccadic amplitudes (Cohen's D = -0.76) and average forward saccadic
      amplitudes were lower (Cohen's D = -0.61). Absolute fixation velocity was higher
      (Cohen's D = 1.02), and overall fixation durations (Cohen's D = 0.58), regression
      durations (Cohen's D = 0.49), and forward saccadic durations (Cohen's D=0.54)
      were longer. mTBI participants had more fixations (Cohen's D = 0.54) and
      regressions per line (Cohen's D = 0.70) and read fewer lines (Cohen's D = -0.38)
      than normal subjects. On the horizontal ramp task, mTBI participants had lower
      weighted smooth pursuit gains (Cohen's D = -0.55). On the horizontal step task,
      mTBI participants had shorter mean fixation times (Cohen's D = -0.55).
      Conclusions: These results suggest vulnerability of the smooth pursuit and
      saccadic systems in mTBI. Eye tracking shows promise as an objective, sensitive
      assessment of damage after mTBI. (ClinicalTrials.gov number, NCT01611194,
      NCT01925963.).

PMID- 30098190
TI  - Change of beta-Zone Parapapillary Atrophy During Axial Elongation: Boramae Myopia
      Cohort Study Report 3.
AB  - Purpose: To investigate changes of beta-zone parapapillary atrophy (PPA) during
      axial elongation. Methods: Change of beta-zone PPA was evaluated by spectral
      domain optical coherence tomography (SD-OCT) in myopic children for 2 years,
      prospectively. Using the infrared images acquired by a fixed scan circle in the
      glaucoma progression analysis (GPA) mode, the retinal pigment epithelial opening
      (RPEO) and the clinical disc margin (CDM) were manually delineated. The area and
      position of beta-zone PPA was calculated as the differences from those of the
      RPEO and CDM, respectively. The beta-zone PPA was further differentiated into
      betaBM PPA (beta-zone PPA with Bruch's membrane [BM]) and gamma-zone PPA (beta
      zone PPA without BM). The change of beta-zone PPA was compared between the first
      and final visits. Results: The area of beta-zone PPA increased in 35 eyes (76%).
      This increase was associated with RPEO area increase and CDM area decrease. The
      center of beta-zone PPA moved along the direction of vascular trunk dragging, but
      to a lesser extent. The beta-zone PPA enlargement was correlated with the extent
      of vascular trunk dragging (P = 0.014). In all eyes with beta-zone PPA increase,
      the gamma-zone portion had increased. Even in childhood, betaBM PPA existed next
      to their gamma-zone PPA in 11 eyes (24%), including 4 eyes that showed increase
      of both gamma-zone and betaBM portion during axial elongation. Conclusions:
      Enlargement of beta-zone PPA during axial elongation was affected by the extent
      and direction of vascular trunk dragging, thus implicating disproportionate
      growth between the retina and sclera.

PMID- 30098187
TI  - Ultrastructural Morphology of the Optic Nerve Head in Aged and Glaucomatous Mice.
AB  - Purpose: To study age- and intraocular pressure-induced changes in the glial
      lamina of the murine optic nerve on the ultrastructural level. Methods: Naive
      C57bl/6 mice at various ages spanning the time between early adulthood (3 months)
      and senescence (30 months) were used in this study. In addition, the intraocular
      pressure (IOP) was increased in a group of young mice by injection of microbeads
      into the anterior chamber. The unmyelinated segments of the optic nerve
      containing the glial lamina were prepared for transmission electron microscopy
      and imaged at high resolution. Results: Axon packing density decreased slightly
      with age. Aging nerves contained higher numbers of enlarged and degenerating
      axons. Mean axonal diameter and in particular the variance of axonal diameter
      correlated well with age. Axonal mitochondria also showed age-dependent signs of
      pathology. The mean diameter of axonal mitochondria increased, and aged axons
      often contained profiles of mitochondria with very few or no cristae. Astrocytic
      mitochondria remained normal even in very old nerves. Changes to axons and axonal
      mitochondria in young glaucomatous nerves were comparable with those of 18- to 30
      month-old naive mice. In addition to axons and mitochondria, aged and
      glaucomatous nerves showed thickening of the blood vessel basement membranes and
      increased deposition of basement membrane collagen. Conclusions: On the
      ultrastructural level, the effects of age and elevated IOP are quite similar. One
      month of elevated IOP seems to have as strongly detrimental effects on the nerve
      as at least 18 months of normal aging.

PMID- 30098191
TI  - Ambient Air Currents Activate Corneal Nerves During Ocular Desiccation in Rats:
      Simultaneous Recordings of Neural Activity and Corneal Temperature.
AB  - Purpose: Previously we found two types of corneal neurons that we hypothesized to
      play an important role in tearing. One type is called low threshold-cold
      sensitive plus dry sensitive (LT-CS + DS), and the other is termed high threshold
      cold sensitive plus dry sensitive (HT-CS + DS). The present study examined
      critical stimuli influencing the activity of these neurons to elucidate
      environmental factors that may trigger this ocular reflex. Methods: Single
      corneal neurons were extracellularly recorded from the trigeminal ganglia in
      response to ocular stimuli that mimic environmental conditions one encounters in
      daily life. They included an ocular desiccation and slight air currents and were
      presented while simultaneously monitoring the ocular surface temperatures (OST)
      in rats. Results: The results showed that the changes in steady state (SS)
      activity of the neurons closely followed the changes in SS OST: during the
      sustained ocular desiccation, neural firing displayed numerous small sudden
      increases in activities ("spiking"); these "spiking" activities of LT-CS + DS
      neurons were replicated by a minute air current that induced slight ocular
      surface cooling of approximately 0.2-0.1 degrees C; and the responses of HT-CS +
      DS neurons showed an inconsistent relationship to the changes in SS OST or
      exhibited little evidence for "spiking" activities. Conclusions: These results
      suggest that LT-CS + DS neurons play a role in the afferent trigger of tearing as
      we face the environment, exposing the cornea to prevailing air currents that
      produce a slight cooling of the ocular surface. By contrast, HT-CS + DS neurons
      may serve to protect the eyes from extreme dryness by eliciting nociception
      evoked tearing when the OST or osmolarity of tears becomes injurious.

PMID- 30098193
TI  - Instability of TCF4 Triplet Repeat Expansion With Parent-Child Transmission in
      Fuchs' Endothelial Corneal Dystrophy.
AB  - Purpose: Fuchs' endothelial corneal dystrophy (FECD) caused by the CTG triplet
      repeat expansion in the TCF4 gene (CTG18.1 locus) is the most common repeat
      expansion disorder. Intergenerational instability of expanded repeats and
      clinical anticipation are hallmarks of other repeat expansion disorders. In this
      study, we examine stability of triplet repeat allele length and FECD disease
      severity in parent-child transmission of the expanded CTG18.1 allele. Methods: We
      studied 44 parent-child transmissions of the mutant expanded CTG18.1 allele from
      26 FECD families. The CTG18.1 polymorphism was genotyped using short tandem
      repeat analysis, triplet repeat primed PCR assay, and Southern blot analysis.
      FECD severity was assessed using modified Krachmer grading (KG) system. Triplet
      repeat length of mutant allele and KG severity were compared between generations.
      Results: Instability of the expanded allele was seen in 14 of 44 (31.8%) parent
      child transmissions, and the likelihood of an unstable event increased with the
      size of the parental allele
      (?(?def?upalpha{?unicode[Times]{x3B1}}?)?(?def?upbeta{?unicode[Times]{x3B2}}?)?(?
      ef?upgamma{?unicode[Times]{x3B3}}?)?(?def?updelta{?unicode[Times]{x3B4}}?)?(?def?
      pvarepsilon{?unicode[Times]{x3B5}}?)?(?def?upzeta{?unicode[Times]{x3B6}}?)?(?def?
      peta{?unicode[Times]{x3B7}}?)?(?def?uptheta{?unicode[Times]{x3B8}}?)?(?def?upiota
      ?unicode[Times]{x3B9}}?)?(?def?upkappa{?unicode[Times]{x3BA}}?)?(?def?uplambda{?u
      icode[Times]{x3BB}}?)?(?def?upmu{?unicode[Times]{x3BC}}?)?(?def?upnu{?unicode[Tim
      s]{x3BD}}?)?(?def?upxi{?unicode[Times]{x3BE}}?)?(?def?upomicron{?unicode[Times]{x
      BF}}?)?(?def?uppi{?unicode[Times]{x3C0}}?)?(?def?uprho{?unicode[Times]{x3C1}}?)?(
      def?upsigma{?unicode[Times]{x3C3}}?)?(?def?uptau{?unicode[Times]{x3C4}}?)?(?def?u
      upsilon{?unicode[Times]{x3C5}}?)?(?def?upphi{?unicode[Times]{x3C6}}?)?(?def?upchi
      ?unicode[Times]{x3C7}}?)?(?def?uppsy{?unicode[Times]{x3C8}}?)?(?def?upomega{?unic
      de[Times]{x3C9}}?)?(?def?bialpha{?boldsymbol{?alpha}}?)?(?def?bibeta{?boldsymbol{
      beta}}?)?(?def?bigamma{?boldsymbol{?gamma}}?)?(?def?bidelta{?boldsymbol{?delta}}?
      ?(?def?bivarepsilon{?boldsymbol{?varepsilon}}?)?(?def?bizeta{?boldsymbol{?zeta}}?
      ?(?def?bieta{?boldsymbol{?eta}}?)?(?def?bitheta{?boldsymbol{?theta}}?)?(?def?biio
      a{?boldsymbol{?iota}}?)?(?def?bikappa{?boldsymbol{?kappa}}?)?(?def?bilambda{?bold
      ymbol{?lambda}}?)?(?def?bimu{?boldsymbol{?mu}}?)?(?def?binu{?boldsymbol{?nu}}?)?(
      def?bixi{?boldsymbol{?xi}}?)?(?def?biomicron{?boldsymbol{?micron}}?)?(?def?bipi{?
      oldsymbol{?pi}}?)?(?def?birho{?boldsymbol{?rho}}?)?(?def?bisigma{?boldsymbol{?sig
      a}}?)?(?def?bitau{?boldsymbol{?tau}}?)?(?def?biupsilon{?boldsymbol{?upsilon}}?)?(
      def?biphi{?boldsymbol{?phi}}?)?(?def?bichi{?boldsymbol{?chi}}?)?(?def?bipsy{?bold
      ymbol{?psy}}?)?(?def?biomega{?boldsymbol{?omega}}?)?(?def?bupalpha{?unicode[Times
      {x1D6C2}}?)?(?def?bupbeta{?unicode[Times]{x1D6C3}}?)?(?def?bupgamma{?unicode[Time
      ]{x1D6C4}}?)?(?def?bupdelta{?unicode[Times]{x1D6C5}}?)?(?def?bupepsilon{?unicode[
      imes]{x1D6C6}}?)?(?def?bupvarepsilon{?unicode[Times]{x1D6DC}}?)?(?def?bupzeta{?un
      code[Times]{x1D6C7}}?)?(?def?bupeta{?unicode[Times]{x1D6C8}}?)?(?def?buptheta{?un
      code[Times]{x1D6C9}}?)?(?def?bupiota{?unicode[Times]{x1D6CA}}?)?(?def?bupkappa{?u
      icode[Times]{x1D6CB}}?)?(?def?buplambda{?unicode[Times]{x1D6CC}}?)?(?def?bupmu{?u
      icode[Times]{x1D6CD}}?)?(?def?bupnu{?unicode[Times]{x1D6CE}}?)?(?def?bupxi{?unico
      e[Times]{x1D6CF}}?)?(?def?bupomicron{?unicode[Times]{x1D6D0}}?)?(?def?buppi{?unic
      de[Times]{x1D6D1}}?)?(?def?buprho{?unicode[Times]{x1D6D2}}?)?(?def?bupsigma{?unic
      de[Times]{x1D6D4}}?)?(?def?buptau{?unicode[Times]{x1D6D5}}?)?(?def?bupupsilon{?un
      code[Times]{x1D6D6}}?)?(?def?bupphi{?unicode[Times]{x1D6D7}}?)?(?def?bupchi{?unic
      de[Times]{x1D6D8}}?)?(?def?buppsy{?unicode[Times]{x1D6D9}}?)?(?def?bupomega{?unic
      de[Times]{x1D6DA}}?)?(?def?bupvartheta{?unicode[Times]{x1D6DD}}?)?(?def?bGamma{?b
      {?Gamma}}?)?(?def?bDelta{?bf{?Delta}}?)?(?def?bTheta{?bf{?Theta}}?)?(?def?bLambda
      ?bf{?Lambda}}?)?(?def?bXi{?bf{?Xi}}?)?(?def?bPi{?bf{?Pi}}?)?(?def?bSigma{?bf{?Sig
      a}}?)?(?def?bUpsilon{?bf{?Upsilon}}?)?(?def?bPhi{?bf{?Phi}}?)?(?def?bPsi{?bf{?Psi
      }?)?(?def?bOmega{?bf{?Omega}}?)?(?def?iGamma{?unicode[Times]{x1D6E4}}?)?(?def?iDe
      ta{?unicode[Times]{x1D6E5}}?)?(?def?iTheta{?unicode[Times]{x1D6E9}}?)?(?def?iLamb
      a{?unicode[Times]{x1D6EC}}?)?(?def?iXi{?unicode[Times]{x1D6EF}}?)?(?def?iPi{?unic
      de[Times]{x1D6F1}}?)?(?def?iSigma{?unicode[Times]{x1D6F4}}?)?(?def?iUpsilon{?unic
      de[Times]{x1D6F6}}?)?(?def?iPhi{?unicode[Times]{x1D6F7}}?)?(?def?iPsi{?unicode[Ti
      es]{x1D6F9}}?)?(?def?iOmega{?unicode[Times]{x1D6FA}}?)?(?def?biGamma{?unicode[Tim
      s]{x1D71E}}?)?(?def?biDelta{?unicode[Times]{x1D71F}}?)?(?def?biTheta{?unicode[Tim
      s]{x1D723}}?)?(?def?biLambda{?unicode[Times]{x1D726}}?)?(?def?biXi{?unicode[Times
      {x1D729}}?)?(?def?biPi{?unicode[Times]{x1D72B}}?)?(?def?biSigma{?unicode[Times]{x
      D72E}}?)?(?def?biUpsilon{?unicode[Times]{x1D730}}?)?(?def?biPhi{?unicode[Times]{x
      D731}}?)?(?def?biPsi{?unicode[Times]{x1D733}}?)?(?def?biOmega{?unicode[Times]{x1D
      34}}?)?(P = 5.9 ?times {10^{ - 3}}?)). A tendency for contraction was seen in
      transmission of large alleles (repeat length > 120), whereas intermediate alleles
      (repeat length between 77 and 120) had predilection for further expansion (?(P =
      1.3 ?times {10^{ - 3}}?)). Although we noted increased KG severity in the
      offspring in three pairs, none of these transmissions were associated with allele
      instability. Conclusions: We observed instability of the TCF4 triplet repeat
      expansion in nearly a third of parent-child transmissions. Large mutant CTG18.1
      alleles are prone to contraction, whereas intermediate mutant alleles tend to
      expand when unstably transmitted. Intergenerational instability of TCF4 repeat
      expansion has implications on FECD disease inheritance.

PMID- 30098195
TI  - Differential Distribution of Laminin N-Terminus alpha31 Across the Ocular
      Surface: Implications for Corneal Wound Repair.
AB  - Purpose: Laminin N-terminus (LaNt) alpha31 is a relatively unstudied protein
      derived from the laminin alpha3 gene but structurally similar to netrins. LaNt
      alpha31 has, to date, been investigated only in two-dimensional (2D) keratinocyte
      culture where it influences cell migration and adhesion, processes integral to
      wound repair. Here we investigated LaNt alpha31 distribution in ocular surface
      epithelium, during limbal stem cell activation, and corneal wound healing.
      Methods: Human, mouse, and pig eyes, ex vivo limbal explant cultures, and alkali
      burn wounds were processed for immunohistochemistry with antibodies against LaNt
      alpha31 along with progenitor cell-associated proteins. LaNt alpha31 expression
      was induced via adenoviral transduction into primary epithelial cells isolated
      from limbal explants, and cell spreading and migration were analyzed using live
      imaging. Results: LaNt alpha31 localized to the basal layer of the conjunctival,
      limbal, and corneal epithelial cells. However, staining was nonuniform with
      apparent subpopulation enrichment, and some suprabasal reactivity was also noted.
      This LaNt alpha31 distribution largely matched that of keratin 15, epidermal
      growth factor receptor, and transformation-related protein 63alpha (p63alpha),
      and displayed similar increases in expression in activated limbal explants.
      During active alkali burn wound repair, LaNt alpha31 displayed increased
      expression in limbal regions and loss of basal restriction within the cornea.
      Distribution returned to predominately basal cell restricted once the wounded
      epithelium matured. Cultured corneal epithelial cells expressing LaNt alpha31
      displayed increased 2D area and reduced migration, suggesting a functional link
      between this protein and key wound repair activities. Conclusions: These data
      place LaNt alpha31 in position to influence laminin-dependent processes including
      wound repair and stem cell activation.

PMID- 30098194
TI  - Extended Intravitreal Rabbit Eye Residence of Nanoparticles Conjugated With
      Cationic Arginine Peptides for Intraocular Drug Delivery: In Vivo Imaging.
AB  - Purpose: Drug delivery by intravitreal injection remains problematic, small
      agents and macromolecules both clearing rapidly. Typical carriers use
      microparticles (>2 MUm), with size-related liabilities, to slow diffusion. We
      recently described cationic nanoparticles (NP) where conjugated Arg peptides
      prolonged residence in rat eyes, through ionic interaction with vitreal poly
      anions. Here we extended this strategy to in vivo tracking of NP-conjugate (NPC)
      clearance from rabbit eyes. Relating t1/2 to zeta potential, and varied dose, we
      estimated the limits of this charge-based delivery system. Methods: NPC carried
      covalently attached PEG8-2Arg or PEG8-3Arg pentapeptides, having known sequences
      from human eye proteins. Peptides were conjugated (61-64 per NPC); each NP/NPC
      also carried a cyanine7 tag (<0.5 dye/particle). In vivo imaging system (IVIS),
      after intravitreal injection, estimated NPC loss by 800-nm photon emission (745
      nm excitation) at 1 to 3-week intervals following initial scan at day 10.
      Results: NPC of 2Arg-peptides or 3Arg-peptides showed clearance t1/2 of 7 days
      and 17 days respectively, unconjugated NP t1/2 was <<5 days. Doses of 90, 180,
      and 360 MUg of PEG8-2Arg NPC were compared. The lower doses showed dose
      proportional day-10 concentration, and similar clearance. Higher early loss was
      seen with a 360-MUg dose, exceeding rabbit vitreal binding capacity. No
      inflammation was observed. Conclusions: This type of cationic NPC can safely
      increase residence t1/2 in a 1 to 3-week range, with dose <100 MUg per mL
      vitreous. Human drug load may then range from 10 to 100 MUg/eye, usefulness
      depending on individual drug potency and release rate, superimposed on extended
      intravitreal residence.

PMID- 30098192
TI  - Genome-Wide Association Study Identifies a Susceptibility Locus for Comitant
      Esotropia and Suggests a Parent-of-Origin Effect.
AB  - Purpose: To identify genetic variants conferring susceptibility to esotropia.
      Esotropia is the most common form of comitant strabismus, has its highest
      incidence in European ancestry populations, and is believed to be inherited as a
      complex trait. Methods: White European American discovery cohorts with
      nonaccommodative (826 cases and 2991 controls) or accommodative (224 cases and
      749 controls) esotropia were investigated. White European Australian and United
      Kingdom cohorts with nonaccommodative (689 cases and 1448 controls) or
      accommodative (66 cases and 264 controls) esotropia were tested for replication.
      We performed a genome-wide case-control association study using a mixed linear
      additive model. Meta-analyses of discovery and replication cohorts were then
      conducted. Results: A significant association with nonaccommodative esotropia was
      discovered (odds ratio [OR] = 1.41, P = 2.84 * 10-09) and replicated (OR = 1.23,
      P = 0.01) at rs2244352 [T] located within intron 1 of the WRB (tryptophan rich
      basic protein) gene on chromosome 21 (meta-analysis OR = 1.33, P = 9.58 * 10-11).
      This single nucleotide polymorphism (SNP) is differentially methylated, and there
      is a statistically significant skew toward paternal inheritance in the discovery
      cohort. Meta-analysis of the accommodative discovery and replication cohorts
      identified an association with rs912759 [T] (OR = 0.59, P = 1.89 * 10-08), an
      intergenic SNP on chromosome 1p31.1. Conclusions: This is the first genome-wide
      association study (GWAS) to identify significant associations in esotropia and
      suggests a parent-of-origin effect. Additional cohorts will permit replication
      and extension of these findings. Future studies of rs2244352 and WRB should
      provide insight into pathophysiological mechanisms underlying comitant
      strabismus.

PMID- 30098197
TI  - Comments on Assays Used to Measure VEGF in the Presence of Anti-VEGF
      Therapeutics.

PMID- 30098196
TI  - MicroRNA-124 Dysregulation is Associated With Retinal Inflammation and
      Photoreceptor Death in the Degenerating Retina.
AB  - Purpose: We sought to determine the role and retinal cellular location of
      microRNA-124 (miR-124) in a neuroinflammatory model of retinal degeneration.
      Further, we explored the anti-inflammatory relationship of miR-124 with a
      predicted messenger RNA (mRNA) binding partner, chemokine (C-C motif) ligand 2
      (Ccl2), which is crucially involved in inflammatory cell recruitment in the
      damaged retina. Methods: Human AMD donor eyes and photo-oxidative damaged (PD)
      mice were labeled for miR-124 expression using in situ hybridization. PDGFRa-cre
      RFP mice were used for Muller cell isolation from whole retinas. MIO-M1
      immortalized cells and rat primary Muller cells were used for in vitro analysis
      of miR-124 expression and its relationship with Ccl2. Therapeutic efficacy was
      tested with intravitreal administration of miR-124 mimic in mice, with
      electroretinography used to determine retinal function. IBA1 immunohistochemistry
      and photoreceptor row counts were used for assessment of inflammation and cell
      death. Results: MiR-124 expression was correlated with progressive retinal
      damage, inflammation, and cell death in human AMD and PD mice. In addition, miR
      124 expression was inversely correlated to Ccl2 expression in mice following PD.
      MiR-124 was localized to both neuronal-like photoreceptors and glial (Muller)
      cells in the retina, with a redistribution from neurons to glia occurring as a
      consequence of PD. Finally, intravitreal administration of miR-124 mimics
      decreased retinal inflammation and photoreceptor cell death, and improved retinal
      function. Conclusions: This study has provided an understanding of the mechanism
      behind miR-124 in the degenerating retina and demonstrates the usefulness of miR
      124 mimics for the modulation of retinal degenerations.

PMID- 30098198
TI  - Author Response: Comments on Assays Used to Measure VEGF in the Presence of Anti
      VEGF Therapeutics.

PMID- 30098199
TI  - Factors Affecting Microvascular Responses in the Bulbar Conjunctiva in Habitual
      Contact Lens Wearers.
AB  - Purpose: To investigate the factors affecting microvascular responses in the
      bulbar conjunctiva of habitual contact lens (HCL) wearers. Methods: A functional
      slit-lamp biomicroscope (FSLB) was used to image the temporal bulbar conjunctiva
      of habitual contact lens (HCL) wearers and non-contact lens (NCL) wearers. The
      vessel diameters and blood flow velocities (BFVs) were measured. Fractal analysis
      using Dbox as vessel density and D0 as vessel complexity were used to
      quantitatively analyze the microvascular network. One eye each of 91 NCL wearers
      and 75 HCL wearers was imaged. Results: The BFV of NCL wearers was 0.50 +/- 0.14
      mm/s, which was negatively correlated with age (r = -0.22, P < 0.05). The BFV,
      vessel diameter, Dbox, and D0 of HCL wearers was significantly higher than NCL
      wearers (P < 0.05). In these HCL wearers, BFVs were positively correlated with
      contact lens (CL) hours of wear per day and CL days of wear per week. BFV, Dbox,
      and D0 were not related to CL years of wear, CL power, CL base curve, and CL
      diameter (P > 0.05). Conclusions: Vascular responses on the bulbar conjunctiva
      occurred in HCL wearers and appeared to be unrelated to sex or age, CL years of
      wear, and lens parameters, indicating that wearing a CL itself may be the
      predominant factor inducing these responses.

PMID- 30098201
TI  - Retinal Microvascular Impairment in the Early Stages of Parkinson's Disease.
AB  - Purpose: To detect the retinal microvascular impairment using optical coherence
      tomography angiography (OCT-A) in patients with Parkinson's disease (PD) and find
      a correlation between the microvascular impairment and the neuronal damage.
      Methods: This is a prospective, observational study including 49 eyes from 38 PD
      patients in their early stages and 34 eyes from 28 healthy controls with
      comparable age range. Macula microvasculature was evaluated with the spectral
      domain optical coherence tomography (SD-OCT) angiography and intraretinal layer
      thickness evaluated with the SD-OCT. A custom algorithm was used for custom
      segmentation of retinal thickness and quantification of the superficial and deep
      microvascular density of the macula, respectively. Results: PD patients showed
      reduced microvascular density in most of the areas of the whole retina. In the
      superficial retinal capillary plexus, statistical difference (P < 0.01) was seen
      in the total annular zone (TAZ), superior, temporal, inferior, and nasal zones.
      In PD patients, there was a strong correlation between the average ganglion cell
      layer and inner plexiform (GCIP) thickness and the TAZ of the superficial
      microvascular density (r = 0.062, P = 0.032). Conclusion: We demonstrated that
      retinal microvascular density decreased in PD patients. The correlation between
      microvascular impairment in the superficial retinal capillary layer and GCIP
      thinning also revealed that the retinal microvascular abnormality may contribute
      to the neurodegeneration in PD patients. OCT-A with quantitative analysis offers
      a new path of study and will likely be useful in the future as an objective
      biomarker for detecting vessel impairment in early stages of PD.

PMID- 30098200
TI  - The Corneal Basement Membranes and Stromal Fibrosis.
AB  - Purpose: The purpose of this review was to provide detailed insights into the
      pathophysiology of myofibroblast-mediated fibrosis (scarring or late haze) after
      corneal injury, surgery, or infection. Method: Literature review. Results: The
      epithelium and epithelial basement membrane (EBM) and/or endothelium and
      Descemet's basement membrane (BM) are commonly disrupted after corneal injuries,
      surgeries, and infections. Regeneration of these critical regulatory structures
      relies on the coordinated production of BM components, including laminins,
      nidogens, perlecan, and collagen type IV by epithelial, endothelial, and
      keratocyte cells. Whether a cornea, or an area in the cornea, heals with
      transparency or fibrosis may be determined by whether there is injury to one or
      both corneal basement membranes (EBM and/or Descemet's BM) and delayed or
      defective regeneration or replacement of the BM. These opaque myofibroblasts, and
      the disordered extracellular matrix these cells produce, persist in the stroma
      until the EBM and/or Descemet's BM is regenerated or replaced. Conclusions:
      Corneal stromal fibrosis (also termed "stromal scarring" or "late haze") occurs
      as a consequence of BM injury and defective regeneration in both the anterior
      (EBM) and posterior (Descemet's BM) cornea. The resolution of fibrosis and return
      of stromal transparency depends on reestablished BM structure and function. It is
      hypothesized that defective regeneration of the EBM or Descemet's BM allows key
      profibrotic growth factors, including transforming growth factor beta-1 (TGF
      beta1) and TGF-beta2, to penetrate the stroma at sustained levels necessary to
      drive the development and maintenance of mature opacity-producing myofibroblasts
      from myofibroblast precursors cells, and studies suggest that perlecan and
      collagen type IV are the critical components in EBM and Descemet's BM that bind
      TGF-beta1, TGF-beta2, platelet-derived growth factor, and possibly other growth
      factors, and regulate their bioavailability and function during homeostasis and
      corneal wound healing.

PMID- 30098202
TI  - A novel fusion gene PLEKHA6-NTRK3 in langerhans cell histiocytosis.
AB  - Langerhans cell histiocytosis (LCH) is the most common histiocytosis with
      constitutive activation of the RAS-RAF-MEK-ERK (MAPKinase) cell signaling
      pathway. We analyzed 89 cases of BRAF and MAP2K1 mutations by Sanger sequencing,
      of which 18 cases showed that these two gene mutations are negative. Whole genome
      sequencing of suitable specimens in these negative cases revealed a translocation
      from the 3 intron of PLEKHA6 to the 13 intron of NTRK3 in one case. We identified
      that this translocation could cause a novel fusion mutation, PLEKHA6-NTRK3.
      Overexpression of the PLEKHA6-NTRK3 mutant in NIH 3T3 cells enhanced MAPKinase
      pathway activation, promote cell growth. Our result suggested that a new mutation
      need be included in LCH molecular screening panel to better define its prevalence
      in LCH.

PMID- 30098203
TI  - Acetylcholinesterase Inhibitors: Start Low or Risk Going Slow?

PMID- 30098207
TI  - Acidic extracellular environment affects miRNA expression in tumors in vitro and
      in vivo.
AB  - Hypoxia can control the expression of miRNAs in tumors which play an important
      role for the control of the malignant behavior. The aim of the study was to
      analyze whether extracellular acidosis, a common feature of tumors, also has an
      impact on the miRNA expression in isolated cells as well as in solid tumors.
      MiRNA expression was analyzed in two rat tumor cell lines (AT1 prostate and
      Walker-256 mammary carcinomas) by NGS and qPCR. In vivo the same cell lines were
      implanted subcutaneously and the tumor pH was modulated by inspiratory hypoxia
      and inhibition of the respiratory chain. In addition, the expression of five
      genes (Brip1, Ercc6l, Ikbke, Per3, Tlr5) which are potential targets of the
      miRNAs were analyzed on mRNA level. Screening showed that 38 (AT1) resp. 41
      (Walker-256) miRNAs were pH-dependent. Validation by qPCR revealed that only 4
      miRNAs were consistently regulated in both cell lines: miR-183, miR-203a, miR-215
      and miR-7a. The expression of miR-7a was increased by low pH whereas all others
      were decreased. In the tumors in vivo all 4 miRNAs were down-regulated. The
      potential targets showed pH dependency in both cell lines. In conclusion,
      extracellular acidosis regulates the expression of miRNAs in vitro and in vivo.
      The expression of targets of these miRNAs were also pH-dependent. The pH may
      therefore affect the biological behavior of tumors via miRNAs. This article is
      protected by copyright. All rights reserved.

PMID- 30098204
TI  - The inflammasomes, immune guardians at defence barriers.
AB  - As a result of its strategic location, the epithelium is constantly exposed to a
      wide variety of pathogen and danger signals. Traditionally, the epithelium has
      been perceived as a defensive but passive barrier; however, it has now become
      evident that the epithelium senses and actively responds to these signals in
      order to maintain barrier homeostasis and contributes to the inflammatory
      response. One way it does this is by producing pro-inflammatory cytokines
      including interleukin-1beta (IL-1beta) and IL-18. These two cytokines are
      synthesized as inactive precursors, the maturation of which is mediated by pro
      inflammatory caspases after the activation and assembly of macromolecular
      complexes called inflammasomes. Epithelial cells express a large panel of
      inflammasome components, and although the molecular mechanisms underlying the
      activation of these complexes in haematopoietic cells are well understood, how
      epithelial cells react to danger signals to activate the inflammasome remains
      unclear. We review and discuss how different inflammasomes contribute to barrier
      homeostasis and inflammation at several barrier sites, their mechanisms and how
      their aberrant regulation contributes to disease at the different epithelia.

PMID- 30098208
TI  - The association between birth order and childhood leukemia may be modified by
      paternal age and birth weight. Pooled results from the International Childhood
      Cancer Cohort Consortium (I4C).
AB  - The "delayed infection hypothesis" states that a paucity of infections in early
      childhood may lead to higher risks of childhood leukemia (CL), especially acute
      lymphoblastic leukemia (ALL). Using prospectively collected data from six
      population-based birth cohorts we studied the association between birth order (a
      proxy for pathogen exposure) and CL. We explored whether other birth or parental
      characteristics modify this association. With 2.2 * 106 person-years of follow
      up, 185 CL and 136 ALL cases were ascertained. In Cox proportional hazards
      models, increasing birth order (continuous) was inversely associated with CL and
      ALL; hazard ratios (HR) = 0.88, 95% confidence interval (CI): (0.77-0.99) and
      0.85: (0.73-0.99), respectively. Being later-born was associated with similarly
      reduced hazards of CL and ALL compared to being first-born; HRs = 0.78: 95% CI:
      0.58-1.05 and 0.73: 0.52-1.03, respectively. Successive birth orders were
      associated with decreased CL and ALL risks (P for trend 0.047 and 0.055,
      respectively). Multivariable adjustment somewhat attenuated the associations. We
      found statistically significant and borderline interactions between birth weight
      (p = 0.024) and paternal age (p = 0.067), respectively, in associations between
      being later-born and CL, with the lowest risk observed for children born at <3 kg
      with fathers aged 35+ (HR = 0.18, 95% CI: 0.06-0.50). Our study strengthens the
      theory that increasing birth order confers protection against CL and ALL risks,
      but suggests that this association may be modified among subsets of children with
      different characteristics, notably advanced paternal age and lower birth weight.
      It is unclear whether these findings can be explained solely by infectious
      exposures.

PMID- 30098206
TI  - Interleukin-33 contributes to disease severity in Dengue virus infection in mice.
AB  - The excessive inflammation often present in patients with severe dengue infection
      is considered both a hallmark of disease and a target for potential treatments.
      Interleukin-33 (IL-33) is a pleiotropic cytokine with pro-inflammatory effects
      whose role in dengue has not been fully elucidated. We demonstrate that IL-33
      plays a disease-exacerbating role during experimental dengue infection in
      immunocompetent mice. Mice infected with dengue virus serotype 2 (DENV2) produced
      high levels of IL-33. DENV2-infected mice treated with recombinant IL-33
      developed markedly more severe disease compared with untreated mice as assessed
      by mortality, granulocytosis, liver damage and pro-inflammatory cytokine
      production. Conversely, ST2-/- mice (deficient in IL-33 receptor) infected with
      DENV2 developed significantly less severe disease compared with wild-type mice.
      Furthermore, the increased disease severity and the accompanying pathology
      induced by IL-33 during dengue infection were reversed by the simultaneous
      treatment with a CXCR2 receptor antagonist (DF2156A). Together, these results
      indicate that IL-33 plays a disease-exacerbating role in experimental dengue
      infection, probably driven by CXCR2-expressing cells, leading to elevated pro
      inflammatory response-mediated pathology. Our results also indicate that IL-33 is
      a potential therapeutic target for dengue infection.

PMID- 30098205
TI  - The impact of inflationary cytomegalovirus-specific memory T cells on anti-tumour
      immune responses in patients with cancer.
AB  - Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV
      infection contributes to the accumulation of functional antigen-specific CD8+ T
      cell pools with an effector-memory phenotype and enrichment of these immune cells
      in peripheral organs. We review here this 'memory T-cell inflation' phenomenon
      and associated factors including age and sex. 'Collateral damage' due to CMV
      directed immune reactivity may occur in later stages of life - arising from CMV
      specific immune responses that were beneficial in earlier life. CMV may be
      considered an age-dependent immunomodulator and a double-edged sword in editing
      anti-tumour immune responses. Emerging evidence suggests that CMV is highly
      prevalent in patients with a variety of cancers, particularly glioblastoma. A
      better understanding of CMV-associated immune responses and its implications for
      immune senescence, especially in patients with cancer, may aid in the design of
      more clinically relevant and tailored, personalized treatment regimens. 'Memory T
      cell inflation' could be applied in vaccine development strategies to enrich for
      immune reactivity where long-term immunological memory is needed, e.g. in long
      term immune memory formation directed against transformed cells.

PMID- 30098210
TI  - A fast curtain-removal method for 3D FIB-SEM images of heterogeneous minerals.
AB  - : The focused ion beam-scanning electron microscope (FIB-SEM) system plays a
      crucial role in the research of shale reservoirs. It enables visualise nano-scale
      pores and helps characterise unconventional reservoirs. In this system, FIB
      removes a thin layer and SEM generates a high-resolution grey-scale image of this
      fresh surface. By iteratively using FIB and SEM, we can create a series of 2D
      images. Through stacking these images, a 3D model of a rock sample is generated.
      However, curtain noise of varying intensity often appears in FIB-SEM data. Its
      presence can cause a severe effect on estimation of rock properties, such as
      porosity and permeability, and lead to incorrect interpretation of the FIB-SEM
      image. Because curtain noise can be falsely identified as needle-shaped pore
      throats based on grey-scale image segmentation. Thus it is imperative to decrease
      curtain noise before segmentation in order to obtain a better understanding of a
      rock sample. In this paper, we propose a novel approach considering mineral
      density to decrease curtain noise and compare its results with several
      conventional used methods. LAY DESCRIPTION: The focused ion beam-scanning
      electron microscope (FIB-SEM) system plays a crucial role in the research of
      shale reservoirs. It enables visualise nano-scale pores and helps characterise
      unconventional reservoirs. In this system, FIB removes a thin layer and SEM
      generates a high-resolution grey-scale image of this fresh surface. By
      iteratively using FIB and SEM, we can create a series of 2D images. Through
      stacking these images, a 3D model of a rock sample is generated. However, curtain
      noise of varying intensity often appears in FIB-SEM data. Its presence can cause
      a severe effect on estimation of rock properties, such as porosity and
      permeability, and lead to incorrect interpretation of the FIB-SEM image. Because
      curtain noise can be falsely identified as needle-shaped pore throats based on
      grey-scale image segmentation. Thus it is imperative to decrease curtain noise
      before segmentation in order to obtain a better understanding of a rock sample.
      In this paper, we propose a novel approach considering mineral density to
      decrease curtain noise and compare its results with several conventional used
      methods.

PMID- 30098209
TI  - Avian predation intensity as a driver of clinal variation in colour morph
      frequency.
AB  - Phenotypic variation provides the framework for natural selection to work upon,
      enabling adaptive evolution. One of the most discernible manifestations of
      phenotypic variability is colour variation. When this variation is discrete,
      genetically based colour pattern morphs occur simultaneously within a population.
      Why and how colour polymorphisms are maintained is an evolutionary puzzle.
      Several evolutionary drivers have been hypothesized as influencing clinal
      patterns of morph frequency, with spatial variation in climate and predation
      being considered especially important. Despite this, no study has examined both
      of their roles simultaneously. The aims of this study were to: (a) examine the
      covariation of physiology, environmental variables and colouration at a local
      scale; and (b) determine if these factors and their interplay explain broad
      clinal variation in morph frequency. We used the lizard Liopholis whitii as a
      model system, as this species displays a discrete, heritable polymorphism for
      colour pattern (plain-backed, patterned morphs) whose morph frequency varies
      latitudinally. We measured reflectance, field activity temperatures and
      microhabitat structure to test for differences in crypsis, thermal biology and
      microhabitat selection of patterned and plain-backed morphs within a single
      population where colour morphs occur sympatrically. We then used data from the
      literature to perform a broad-scale analysis to identify whether these factors
      also explained the latitudinal variation of morph frequency in this species. At
      the local scale, plain-backed morphs were found to be less cryptic than patterned
      morphs while no other differences were detected in terms of thermal biology,
      dorsal reflectance and microhabitat use. At a broader scale, predation was the
      most influential factor mediating morph frequency across latitudes. However, the
      observed pattern of morph frequency is opposite to what the modelling results
      suggest in that the incidence of the least cryptic morph is highest where
      predation pressure is most severe. Clinal variation in the level of background
      matching between morphs or the potential reproductive advantage by the plain
      backed morph may, instead, be driving the observed morph frequency. Together,
      these results provide key insights into the evolution of local adaptation as well
      as the ecological forces involved in driving the dynamics of colour polymorphism.

PMID- 30098212
TI  - Breast ultrasonography (BU) in the screening protocol for women at hereditary
      familial risk of breast cancer: has the time come to rethink the role of BU
      according to different risk categories?
AB  - This article evaluates the breast cancer (BC) screening efficacy of biannual
      ultrasound (US) in three different risk categories. In a single-center,
      prospective, nonrandomized comparison study, BRCA mutation carriers and women
      with high risk (HR) or intermediate risk (IR) received mammography (MMG),
      ultrasound, (US) and Magnetic Resonance Imaging (MRI), scheduled according to the
      risk categories. Single and combined sensitivity were evaluated in specific
      groups of risk and the US performance at six-monthly interval was notably
      considered. Among 2,313 asymptomatic women at different risk (136 mutation
      carriers, 1,749 at HR and 428 at IR) 211 developed a BC, of which 193 (91.5%)
      were screen detected BC (SDBC) and 18 (8.5%) were interval BC (IBC). The SDBC
      detection rate (DR) was 11.2 per 1.000 person-years (37.9, 8.5 and 16.1 for BRCA,
      HR and IR, respectively); 116 BC were detected by MMG (DR = 6.6 * 1,000 persons
      years), 62 by US (DR = 3.6 * 1,000 persons-years) and 15 by MRI, that was applied
      only in 60 BRCA women (DR = 37 * 1,000 persons-years). At the six-monthly US, 52
      BC were detected (DR = 3.0 * 1,000 persons/years), of which 8 were BRCA-related.
      The most sensitive technique was MRI (93.7%) followed by MMG (55%) and US
      (29.4%). Combined sensitivity for MMG plus US was 100% in HR and 80.4% for IR
      women (p < 0.01). In BRCA mutated patients, MRI alone with annual US performed
      after six months, could be offered. In HR patients, MMG plus biannual US provide
      the most sensitive diagnosis and for IR group an annual MMG could be sufficient.

PMID- 30098211
TI  - Association between Development of Dementia and Use of Benzodiazepines: A
      Systematic Review and Meta-Analysis.
AB  - STUDY OBJECTIVE: The use of benzodiazepines and the development of dementia is
      controversial, with studies indicating that benzodiazepines could be either a
      protective factor or a risk factor for dementia, or no association may exist
      between the two. Our objective was to identify whether such an association
      exists. DESIGN: Systematic review and meta-analysis of 12 prospective and
      retrospective cohort studies and case-control studies. PARTICIPANTS: A total of
      981,133 (in the systematic review) and 980,860 (in the meta-analysis) adults or
      elderly individuals. MEASUREMENTS AND MAIN RESULTS: A search of the PubMed,
      LILACS, and Cochrane Central Register of Controlled Trials databases, as well as
      a manual search of the reference lists of the included publications and reviews,
      was performed. We included studies that reported the incidence of dementia and in
      ever users of benzodiazepines. Data were analyzed by using a random effects model
      in R software. Quality of the evidence was assessed with the Grading of
      Recommendations Assessment, Development and Evaluation (GRADE) certainty ratings
      system. The results of the main meta-analysis suggest that benzodiazepines can be
      a risk factor for developing dementia (odds ratio 1.38, 95% confidence interval
      1.07-1.77; I2 = 98%; 95% prediction interval 0.58-3.25; very low certainty).
      CONCLUSION: Our results suggest an association between the use of benzodiazepines
      and the development of dementia. However, the current evidence lacks the power to
      infer differences between the effects of Alzheimer's disease and vascular
      dementias, long-acting and short-acting benzodiazepines, and various exposure
      loads (duration and dose). Future long-term prospective cohort studies are
      necessary, with adequate adjustments for confounding variables, strategies to
      minimize reverse causality, reporting of subgroups aimed at greater homogeneity
      of findings, adequate statistical power to identify high-magnitude effects, and
      defined daily dose analyses for dose-response gradient.

PMID- 30098213
TI  - Simple Co-Occurrence Statistics Reproducibly Predict Association Ratings.
AB  - What determines human ratings of association? We planned this paper as a test for
      association strength (AS) that is derived from the log likelihood that two words
      co-occur significantly more often together in sentences than is expected from
      their single word frequencies. We also investigated the moderately correlated
      interactions of word frequency, emotional valence, arousal, and imageability of
      both words (r's <= .3). In three studies, linear mixed effects models revealed
      that AS and valence reproducibly account for variance in the human ratings. To
      understand further correlated predictors, we conducted a hierarchical cluster
      analysis and examined the predictors of four clusters in competitive analyses:
      Only AS and word2vec skip-gram cosine distances reproducibly accounted for
      variance in all three studies. The other predictors of the first cluster (number
      of common associates, (positive) point-wise mutual information, and word2vec CBOW
      cosine) did not reproducibly explain further variance. The same was true for the
      second cluster (word frequency and arousal); the third cluster (emotional valence
      and imageability); and the fourth cluster (consisting of joint frequency only).
      Finally, we discuss emotional valence as an important dimension of semantic
      space. Our results suggest that a simple definition of syntagmatic word
      contiguity (AS) and a paradigmatic measure of semantic similarity (skip-gram
      cosine) provide the most general performance-independent explanation of
      association ratings.

PMID- 30098215
TI  - A risk-based approach to identifying oligometastatic disease on imaging.
AB  - Recognition of <3 metastases in <2 organs, particularly in cancers with a known
      predisposition to oligometastatic disease (OMD) (colorectal, prostate, renal,
      sarcoma and lung), offers the opportunity to focally treat the lesions identified
      and confers a survival advantage. The reliability with which OMD is identified
      depends on the sensitivity of the imaging technique used for detection and may be
      predicted from phenotypic and genetic factors of the primary tumour, which
      determine metastatic risk. Whole-body or organ-specific imaging to identify
      oligometastases requires optimization to achieve maximal sensitivity. Metastatic
      lesions at multiple locations may require a variety of imaging modalities for
      best visualisation because the optimal image contrast is determined by tumour
      biology. Newer imaging techniques used for this purpose require validation.
      Additionally, rationalisation of imaging strategies is needed, particularly with
      regard to timing of imaging and follow-up studies. This article reviews the
      current evidence for the use of imaging for recognising OMD and proposes a risk
      based roadmap for identifying patients with true OMD, or at risk of metastatic
      disease likely to be OM.

PMID- 30098214
TI  - YY1 binds to the E3' enhancer and inhibits the expression of the immunoglobulin
      kappa gene via epigenetic modifications.
AB  - The rearrangement and expression of immunoglobulin genes are regulated by
      enhancers and their binding transcriptional factors that activate or suppress the
      activities of the enhancers. The immunoglobulin kappa (Igkappa) gene locus has
      three important enhancers: the intrinsic enhancer (Ei), 3' enhancer (E3'), and
      distal enhancer (Ed). Ei and E3' are both required for Igkappa gene rearrangement
      during early stages of B-cell development, whereas optimal expression of the
      rearranged Igkappa gene relies on both E3' and Ed. The transcription factor YY1
      affects the expression of many genes involved in B-cell development, probably by
      mediating interactions between their enhancers and promoters. Herein, we found
      that YY1 binds to the E3' enhancer and suppresses Igkappa expression in B
      lymphoma cells by epigenetically modifying the enhancer. Knocking down YY1
      enhanced Igkappa expression, which was associated with increased levels of E2A
      (encoded by the TCF3 gene) and its binding to the E3' enhancer. Moreover, in
      germinal centre B cells and plasma cells, YY1 expression was reversely associated
      with Igkappa levels, implying that YY1 might facilitate antibody affinity
      maturation in germinal centre B cells through the transient attenuation of
      Igkappa expression.

PMID- 30098216
TI  - Prophylactic infusion of calcium gluconate to prevent a symptomatic fall in
      plasma ionized calcium during therapeutic plasma exchange: A comparison of two
      methods.
AB  - We compared two methods of calcium gluconate infusion to maintain plasma ionized
      calcium ([Ca2+ ]) during therapeutic plasma exchange (TPE) performed using the
      Spectra Optia Apheresis System. Method A, our legacy method, consisted of adding
      5 mL of 10% calcium gluconate to each 500 mL bottle of 5% albumin replacement
      fluid. Method B used an accessory IV infusion of calcium gluconate (2 g in 50 mL
      of 0.9% NaCl starting at 25 mL/h). Plasma [Ca2+ ] was measured at 20-minute
      intervals, and symptoms of hypocalcemia were recorded during TPE. Baseline [Ca2+
      ] was the same (P = 0.616), as was total acid citrate dextrose Formula A used (P
      = 0.865), with either method. TPE with method A used 2.62 +/- 0.52 g of calcium
      gluconate vs 1.13 +/- 0.27 g with method B (P < 0.001). [Ca2+] remained stable
      with method A (P = 0.251), but fell on average by 5% with method B (P < 0.05).
      Hypocalcemic symptoms were reported in 0 of 23 TPE with method A and 2 of 24 TPE
      with method B. We conclude that both methods A and B prevent a symptomatic fall
      in plasma [Ca2+ ] during TPE. Method B requires significantly less calcium
      gluconate than does method A.

PMID- 30098217
TI  - A qualitative study exploring women's health behaviours after a pregnancy with
      gestational diabetes to inform the development of a diabetes prevention strategy.
AB  - AIM: To inform targeted interventions for women with gestational diabetes
      mellitus (GDM) by exploring the factors that influence their health behaviours
      and their preferences for lifestyle support. METHODS: Participants were women
      with previous GDM taken from a diverse inner-city UK population. Data collection
      involved focus groups (n = 35 women in six groups) and semi-structured interviews
      (n = 15 women). The transcribed data were analysed using framework analysis.
      RESULTS: Eight themes relating to factors influencing health behaviour were
      identified: psychological legacy of pregnancy, relationships with healthcare
      professionals, physical impacts of pregnancy, social support and cultural norms,
      life-scheduling, understanding and risk perception, appetite regulation, and
      prioritization of the baby. The women's recommendations for intervention
      components included addressing the emotional stress of pregnancy; conveying
      personalized risk in a motivational way, adopting a family-centered approach,
      focusing on women's health rather than just the infant's, and developing flexible
      interventions. These recommendations were used to construct a model integrating
      the behaviour-regulating factors with a suggested framework for intervention.
      CONCLUSIONS: This study identified some common drivers that may regulate the
      health behaviours of women following GDM, and recognized some ways to improve
      care to impact on this. Interventions for diabetes prevention in this population
      need to address factors at both the individual and systemic levels.

PMID- 30098219
TI  - Is insulin pump therapy effective in Type 1 diabetes?
AB  - There continues to be uncertainty about the effectiveness in Type 1 diabetes of
      insulin pump therapy (continuous subcutaneous insulin infusion, CSII) vs.
      multiple daily insulin injections (MDI). This narrative review discusses the
      reasons for this uncertainty, summarizes the current evidence base for CSII and
      suggests some future research needs. There are difficulties in interpreting
      trials of CSII because effectiveness varies widely due to factors such as
      differing baseline control, suboptimal use of best CSII practices, and
      psychological factors, for example, high external locus of control, non-adherence
      and lack of motivation. Many summary meta-analyses are also misleading because of
      poor trial selection (e.g. short duration, obsolete pumps, low baseline rate of
      hypoglycaemia) and reliance on mean effect size for decision-making. Both MDI and
      CSII can achieve strict glycaemic control without hypoglycaemia in some people
      with Type 1 diabetes, especially those who are motivated and have undergone
      structured diabetes education, and with high levels of ongoing input from
      healthcare professionals. CSII is particularly effective in those people with
      Type 1 diabetes who have not achieved target HbA1c levels without disabling
      hypoglycaemia using best attempts with MDI, and here there can be valuable and
      substantial improvement. Insulin pumps are safe, effective and accepted when used
      in newly diagnosed diabetes, particularly in children, where MDI may not be
      practicable. Future research needs include more studies on mortality associated
      with insulin pumps where registry data have suggested lower rates vs. MDI; and
      psychological strategies to improve non-adherence and suboptimal glycaemic
      outcomes on CSII.

PMID- 30098218
TI  - JPMHN report on the 2018 Skellern Lecture and JPHMN Lifetime Achievement Award
      held at the University of Greenwich Maritime Campus, June 14th 2018.

PMID- 30098220
TI  - The modification of mitochondrial energy metabolism and histone of goat somatic
      cells under small molecules compounds induction.
AB  - In recent years, induced pluripotent stem cells (iPSCs) technique is able to
      allow us to generate pluripotency from somatic cells in vitro through the over
      expression of several transcription factors. Normally, viral vectors and
      transcription factors are commonly used on iPSC technique, which could cause many
      barriers on further application. In this study, we attempt to process a new
      method to obtain pluripotency from goat somatic cells in vitro under fully
      chemically defined condition. The results showed that chemically induced
      pluripotent stem cells-like cells (CiPSC-like cells) colonies were generated from
      goat ear fibroblasts by fully small-molecule compounds. Those three dimensions
      colonies were similar with mouse iPSCs in morphology and had strong positive
      alkaline phosphatase (AP) activity and expressed pluripotency related genes OCT4,
      SOX2, NANOG, CDH1, TDGF, GDF3, DAX1, REX1, which determined by RT-PCR. Those
      colonies could also differentiate into different cell types derived from three
      germ layers proved by RT-PCR and immunofluorescence assays. The expression of
      glycolysis related genes about PGAM1, KPYM2 and HXK2 in CiPSC-like colonies
      formation groups were significantly higher than their parental fibroblasts, but
      not in the non-CiPSC-like colonies formation group. The expression of histone
      acetylation and methylation related genes, HAT1 and SMYD3, was not significantly
      up-regulated within different groups compared to their parental fibroblasts,
      respectively. However, the expression of histone methylation related gene, KDM5B,
      was significantly up-regulated on the cells from non-colonies formation group
      compared to parental fibroblasts, but the expression of KDM5B of the cells from
      CiPSC-like cell colonies was not significantly difference compared to that of
      parental fibroblasts. In conclusion, this is the first report that CiPSC-like
      cells could be generated in vitro from goat rather than just mouse under fully
      chemically defined condition. The generation of CiPSC-like colonies may be
      depended on the correct modification of energy metabolism and histone epigenetic
      during the reprogramming, rather than just the over-expression of those
      pluripotency related genes. This study will strongly support us to further
      establish the stable goat CiPSC lines without any integration of exogenous genes.
      This article is protected by copyright. All rights reserved.

PMID- 30098221
TI  - Pre-eclampsia and cardiovascular risk: comparing apples with apples.

PMID- 30098222
TI  - Residential HVAC runtime from smart thermostats: characterization, comparison,
      and impacts.
AB  - In North America, the majority of homes use forced-air systems for heating and
      cooling. The proportion of time these systems operate, or runtime, has a
      significant impact on many building performance parameters. The recent adoption
      of smart thermostats in many North American homes presents a potential data
      source for runtime. Smart thermostat data collected from over 7000 homes were
      compared with nine other investigations and a runtime estimation method based on
      exterior temperature. The smart thermostat runtimes have a median of 18% across
      all homes, but show considerable variation between homes, even at constant
      exterior temperature conditions suggesting that factors besides climate (eg,
      system sizing, user operation) have a significant impact on runtime. Results from
      other investigations suggest that smart thermostat runtimes are consistent with
      other measurement approaches. The practical implications of runtime include the
      impact on central filtration performance. At low to average runtimes, the filter
      efficiency matters much less for effectiveness because the system does not run
      enough for a sufficient air volume to pass through the filter and have a
      substantial impact on particle concentrations. This work illustrates the
      importance of measuring runtime for a particular home, and the value of data
      obtained from smart thermostats.

PMID- 30098224
TI  - Legibility of floor plans and wayfinding satisfaction of residents in Care and
      Attention homes in Hong Kong.
AB  - OBJECTIVE: Focusing on Hong Kong Care and Attention homes which provide
      residential care, meals, personal care and limited nursing care for older people,
      this study aimed to understand the impact of floor plans' legibility (layout and
      complexity) on residents' wayfinding satisfaction and self-reported health
      status. METHODS: A questionnaire survey was conducted in nine Care and Attention
      homes. Space syntax, a well-established method, was used to evaluate the
      legibility of their floor plans via calculating the integration value. RESULTS:
      Familiarity with Care and Attention homes did not influence the residents'
      satisfaction with wayfinding. The integration value had a significant impact on
      residents' satisfaction with wayfinding. No relationship was observed between
      integration value and self-reported health status. CONCLUSION: Increasing
      complexity in floor plans appears to negatively affect residents' wayfinding
      satisfaction. These data suggest that circulation patterns should be improved for
      better wayfinding.

PMID- 30098223
TI  - ABCA1 overexpression worsens colorectal cancer prognosis by facilitating tumour
      growth and caveolin-1-dependent invasiveness, and these effects can be
      ameliorated using the BET inhibitor apabetalone.
AB  - At the time of diagnosis, 20% of patients with colorectal cancer present
      metastasis. Among individuals with primary lesions, 50% of them will develop
      distant tumours with time. Therefore, early diagnosis and prediction of
      aggressiveness is crucial for therapy design and disease prognosis. Tumoral cells
      must undergo significant changes in energy metabolism to meet increased
      structural and energetic demands for cell proliferation, and metabolic
      alterations are considered to be a hallmark of cancer. Here, we present the ATP
      binding cassette transporter (ABCA1), a regulator of cholesterol transport, as a
      new marker for invasion and colorectal cancer survival. ABCA1 is significantly
      overexpressed in patients at advanced stages of colorectal cancer, and its
      overexpression confers proliferative advantages together with caveolin-1
      dependent-increased migratory and invasive capacities. Thus, intracellular
      cholesterol imbalances mediated by ABCA1 overexpression may contribute to primary
      tumour growth and dissemination to distant locations. Furthermore, we demonstrate
      here that increased levels of apolipoprotein A1 (APOA1), a protein involved in
      cholesterol efflux and high-density lipoprotein constitution, in the
      extracellular compartment modulates expression of ABCA1 by regulating COX-2, and
      compensate for ABCA1-dependent excessive export of cholesterol. APOA1 emerges as
      a new therapeutic option to inhibit the promotion of colorectal cancer to
      metastasis by modulating intracellular cholesterol metabolism. Furthermore, we
      propose apabetalone, an orally available small molecule that is currently being
      evaluated in clinical trials for the treatment of atherosclerosis, as a new
      putative therapeutic option to prevent colorectal cancer progression by
      increasing APOA1 expression and regulating reverse transport of cholesterol.

PMID- 30098225
TI  - Prodrug suicide gene therapy for cancer targeted intracellular by mesenchymal
      stem cell exosomes.
AB  - The natural behavior of mesenchymal stem cells (MSCs) and their exosomes in
      targeting tumors is a promising approach for curative therapy. Human tumor tropic
      mesenchymal stem cells (MSCs) isolated from various tissues and MSCs engineered
      to express the yeast cytosine deaminase::uracil phosphoribosyl transferase
      suicide fusion gene (yCD::UPRT-MSCs) released exosomes in conditional medium
      (CM). Exosomes from all tissue specific yCD::UPRT-MSCs contained mRNA of the
      suicide gene in the exosome's cargo. When the CM was applied to tumor cells, the
      exosomes were internalized by recipient tumor cells and in the presence of the
      prodrug 5-fluorocytosine (5-FC) effectively triggered dose-dependent tumor cell
      death by endocytosed exosomes via an intracellular conversion of the prodrug 5-FC
      to 5-fluorouracil. Exosomes were found to be responsible for the tumor inhibitory
      activity. The presence of microRNAs in exosomes produced from naive MSCs and from
      suicide gene transduced MSCs did not differ significantly. MicroRNAs from
      yCD::UPRT-MSCs were not associated with therapeutic effect. MSC suicide gene
      exosomes represent a new class of tumor cell targeting drug acting intracellular
      with curative potential.

PMID- 30098226
TI  - Effects of sclerotic changes on stress concentration in early-stage
      osteonecrosis: A patient-specific, 3D finite element analysis.
AB  - : Stress distribution remains unclear in early-stage osteonecrosis of the femoral
      head (ONFH). To clarify this issue, we generated patient-specific finite element
      models (FEMs) from 51 patients with ONFH. Patients' hips were classified into
      three groups: ONFH without a sclerotic boundary (Stage 1, n = 6), ONFH with a
      sclerotic boundary (Stage 2, n = 10), and ONFH with both a sclerotic boundary and
      <2 mm collapse (Stage 3, n = 35). Four hips without ONFH were used as controls.
      Stress distribution in each FEM was compared with magnetic resonance imaging
      (MRI) and computed tomography (CT) results. Fifteen wholly resected femoral heads
      in Stage 3 hips were assessed by micro-CT. Furthermore, we histologically
      examined three Stage 2 femoral heads that subsequently developed subchondral
      fractures after FEM analyses. In all FEMs of both control and Stage 1 hip, stress
      was equally distributed on the femoral head surface. However, in all FEMs of both
      Stages 2 and 3 hips, stress was concentrated at the lateral boundary of the
      femoral head surface, corresponding to both a low-intensity band on T1-weighted
      MRI images and sclerotic changes on CT. On micro-CT, subchondral fractures
      consistently began at the lateral boundary with sclerotic changes, in which bone
      volume fraction was increased. Histology showed breakage of subchondral plates at
      the junction between necrotic and reparative zones. In early-stage ONFH,
      sclerotic changes caused stress concentration, which can trigger subchondral
      fractures at the lateral boundary. CLINICAL SIGNIFICANCE: Our results will
      clarify the pathogenic mechanism of collapse in ONFH. (c) 2018 Orthopaedic
      Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30098227
TI  - Rising pregabalin use and misuse in Australia: trends in utilization and
      intentional poisonings.
AB  - BACKGROUND AND AIMS: Pregabalin is a gamma-aminobutyric acid (GABA) analogue,
      used to treat neuropathic pain and epilepsy. Pregabalin was registered in
      Australia in 2005, and subsidized publically in 2013. We aimed to describe
      Australian patterns of pregabalin use and intentional poisoning, and identify
      people potentially at high risk of misuse. DESIGN AND SETTING: Population-based
      retrospective cohort study of dispensings in the 10% sample of Australian
      Pharmaceutical Benefits Scheme (July 2012-February 2017); intentional poisoning
      calls to New South Wales Poisons Information Centre (NSWPIC) (2004-2016);
      intentional poisonings in two Australian toxicology service databases; and
      poisoning fatalities in NSW coronial records (2005-2016). PARTICIPANTS: A total
      of 122 572 people dispensed pregabalin, people with intentional pregabalin
      overdoses managed by NSWPIC and the toxicology services and pregabalin-associated
      deaths referred to the NSW coroner. MEASUREMENTS: Trends in dispensing,
      poisoning, death; demographics and patient characteristics, proportion of users
      at high risk of misuse (latent class analysis, LCA) and characteristics of high
      risk users. FINDINGS: Pregabalin dispensing increased by 73 424 per year [95%
      confidence interval (CI) = 61726-85 121 P < 0.001] between 2013 and 2016. NSWPIC
      received 1158 reports of intentional pregabalin poisonings, with a 53.8% increase
      per year, 2005-2016 (95% CI = 44.0-64.2%, P < 0.001). We identified 88 pregabalin
      associated deaths, 57.8% yearly increase (95% CI = 30.0-91.6%, P < 0.001).
      Patients overdosing on pregabalin commonly co-ingested opioids, benzodiazepines
      and illicit drugs, and had high rates of psychiatric and substance use
      comorbidities; 14.7% of pregabalin users were classed by the LCA as at high risk
      of misuse, and were more likely to be younger, male, co-prescribed
      benzodiazepines or opioids, have more individual prescribers and higher
      pregabalin strengths dispensed. CONCLUSIONS: There has been a dramatic increase
      in pregabalin use, poisonings and deaths in Australia since it became subsidized
      publicly in 2013. One in seven Australians dispensed pregabalin appears to be at
      high risk of misuse.

PMID- 30098228
TI  - Re: Randomised controlled trial to estimate reduction in pain after laparoscopic
      surgery when using a combination therapy of intraperitoneal normal saline and the
      pulmonary recruitment manoeuvre.

PMID- 30098230
TI  - Randomized Clinical Trial Comparing Procedural Amnesia and Respiratory Depression
      Between Moderate and Deep Sedation With Propofol in the Emergency Department.
AB  - OBJECTIVES: The objective was to determine if there is a difference in procedural
      amnesia and adverse respiratory events (AREs) between the target sedation levels
      of moderate (MS) and deep (DS) procedural sedation. METHODS: This was a
      prospective, randomized clinical trial of consenting adult patients planning to
      undergo DS with propofol between March 5, 2015, and May 24, 2017. Patients were
      randomized to a target sedation level of MS or DS using the American Society of
      Anesthesiologist's definitions. Drug doses, vital signs, observer's assessment of
      alertness/sedation (OAAS) score, end-tidal CO2 (ETCO2 ), and the need for
      supportive airway maneuvers (SAMs; bag-valve mask use, repositioning, and
      stimulation to induce respirations) were monitored continuously. A standardized
      image was shown every 30 seconds starting 3 minutes before the procedure
      continuing until the patient had returned to baseline after the procedure. Recall
      and recognition of images were assessed 10 minutes after the sedation.
      Subclinical respiratory depression (RD) was defined as SaO2 <= 91%, change in
      ETCO2 >= 10 mm Hg, or absent ETCO2 at any time. The occurrence of RD with a SAM
      was defined as an ARE. Patient satisfaction, pain, and perceived recollection and
      physician assessment of procedure difficulty were collected using visual analog
      scales (VASs). Data were analyzed with descriptive statistics and Wilcoxon rank
      sum test. RESULTS: A total of 107 patients were enrolled: 54 randomized to target
      MS and 53 to DS. Of the patients randomized to target MS, 50% achieved MS and 50%
      achieved DS. In the target DS group, 77% achieved DS and 23% achieved MS. The
      median total propofol dose (mg/kg) was lower in the MS group: MS 1.4 (95%
      confidence interval [CI] = 1.3-1.6, IQR = 1) versus DS 1.8 (95% CI = 1.6-2.0, IQR
      = 0.9). There were no differences in median OAAS during the procedure (MS 2.4 and
      DS 2.8), lowest OAAS (MS 2 and DS 2), percentage of images recalled (MS 4.7% vs.
      DS 3.8%, p = 0.73), or percentage of images recognized (MS 61.1% vs. DS 55%, p =
      0.52). In the MS group, 41% patients had any AREs compared to 42% in the DS group
      (p = 0.77, 95% CI difference = -0.12 to 0.24). The total number of AREs was 23%
      lower in the MS group (p = 0.01, 95% CI = -0.41 to -0.04). There was no
      difference in patient-reported pain, satisfaction, or recollection VAS scores.
      Provider's rating of procedural difficulty and procedural success were similar in
      both groups. CONCLUSIONS: Targeting MS or DS did not reliably result in the
      intended sedation level. Targeting MS, however, resulted in a lower rate of total
      AREs and fewer patients had multiple AREs with no difference in procedural
      recall. As seen in previous reports, patients who achieved MS had less AREs than
      those who achieved DS. Our study suggests that a target of MS provides adequate
      amnesia with less need for supportive airway interventions than a target level of
      DS, despite the fact that it often does not result in intended sedation level.

PMID- 30098229
TI  - Identification of novel GLI1 target genes and regulatory circuits in human cancer
      cells.
AB  - Hedgehog (HH) signaling is involved in many physiological processes, and pathway
      deregulation can result in a wide range of malignancies. Glioma-associated
      oncogene 1 (GLI1) is a transcription factor and a terminal effector of the HH
      cascade. Despite its crucial role in tumorigenesis, our understanding of the GLI1
      cellular targets is quite limited. In this study, we identified multiple new GLI1
      target genes using a combination of different genomic surveys and then subjected
      them to in-depth validation in human cancer cell lines. We were able to validate
      >90% of the new targets, which were enriched in functions involved in
      neurogenesis and regulation of transcription, in at least one type of follow-up
      experiment. Strikingly, we found that RNA editing of GLI1 can modulate effects on
      the targets. Furthermore, one of the top targets, FOXS1, a gene encoding a
      transcription factor previously implicated in nervous system development, was
      shown to act in a negative feedback loop limiting the cellular effects of GLI1 in
      medulloblastoma and rhabdomyosarcoma cells. Moreover, FOXS1 is both highly
      expressed and positively correlated with GLI1 in medulloblastoma samples of the
      Sonic HH subgroup, further arguing for the existence of FOXS1/GLI1 interplay in
      human tumors. Consistently, high FOXS1 expression predicts longer relapse-free
      survival in breast cancer. Overall, our findings open multiple new avenues in HH
      signaling pathway research and have potential for translational implications.

PMID- 30098231
TI  - Importance of physical evaluation using skeletal muscle mass index and body fat
      percentage to prevent sarcopenia in elderly Japanese diabetes patients.
AB  - AIMS/INTRODUCTION: To investigate the prevalence of sarcopenia, its related
      factors and indicators of physical evaluation in elderly diabetes patients.
      MATERIALS AND METHODS: This was a cross-sectional observation study. A total of
      267 diabetes patients (159 men, 108 women) aged >65 years were recruited in the
      present study. Skeletal muscle mass index, grip strength and usual gait speed
      were measured to diagnose sarcopenia according to the Asian Working Group for
      Sarcopenia. Body composition was measured using bioelectrical impedance analysis.
      Body mass index (BMI) and body fat percentage were evaluated in quartiles to
      investigate the relationship with sarcopenia. A multiple logistic regression
      analysis examined sarcopenia-related factors. RESULTS: The prevalence of
      sarcopenia in all participants was 18.7% and increased with age. Sarcopenia
      decreased as BMI increased (P < 0.01, Cochran-Armitage test). In contrast, the
      third quartile body fat percentage group showed the lowest prevalence of
      sarcopenia. A strong positive correlation was observed between body mass and
      skeletal muscle mass indices (R = 0.702-0.682). Multiple logistic regression
      analysis showed that sarcopenia was associated with lower BMI, non-use of
      metformin and lower bone mineral content in men (P < 0.05), and lower bone
      mineral content, lower serum levels of albumin and older age in women (P < 0.05).
      CONCLUSIONS: The present study suggests that diabetes patients with a high body
      fat percentage in addition to low BMI might develop sarcopenia. It is suggested
      that physical management in elderly diabetes patients should be carried out based
      on the evaluation of BMI and body fat percentage to prevent sarcopenia.

PMID- 30098232
TI  - Synthesis and Biological in vitro and in vivo Evaluation of 2-(5-Nitroindazol-1
      yl)ethylamines and Related Compounds as Potential Therapeutic Alternatives for
      Chagas Disease.
AB  - Chagas disease, a neglected tropical disease caused by infection with the
      protozoan parasite Trypanosoma cruzi, is a potentially life-threatening illness
      that affects 5-8 million people in Latin America, and more than 10 million people
      worldwide. It is characterized by an acute phase, which is partly resolved by the
      immune system, but then develops as a chronic disease without an effective
      treatment. There is an urgent need for new antiprotozoal agents, as the current
      standard therapeutic options based on benznidazole and nifurtimox are
      characterized by limited efficacy, toxicity, and frequent failures in treatment.
      In vitro and in vivo assays were used to identify some new low-cost 5
      nitroindazoles as a potential antichagasic therapeutic alternative. Compound 16
      (3-benzyloxy-5-nitro-1-vinyl-1H-indazole) showed improved efficiency and lower
      toxicity than benznidazole in both in vitro and in vivo experiments, and its
      trypanocidal activity seems to be related to its effect at the mitochondrial
      level. Therefore, compound 16 is a promising candidate for the development of a
      new anti-Chagas agent, and further preclinical evaluation should be considered.

PMID- 30098233
TI  - Triamterene-Grafted Graphitic Carbon Nitride with Electronic Potential
      Redistribution for Efficient Photocatalytic Hydrogen Evolution.
AB  - In this study, a photocatalyst with a distorted skeleton and synthesized by
      grafting triamterene onto graphitic carbon nitride (g-C3 N4 ) frameworks was
      prepared. The pteridine ring of the triamterene-based nitrogen-enriched organic
      structure functions as a trapped electron site owing to its inductive effect. The
      benzene ring in triamterene plays an important role in the even dispersion of
      electrons by a conjugative effect. Redistribution of the intramolecular
      electronic potential is caused by a synergistic effect between the pteridine and
      benzene rings of triamterene and promotes separation and migration of the
      photoinduced charge carriers. After coupling with triamterene, the pi electrons
      of g-C3 N4 are relocated; that is, the intrinsic electronic and band structures
      of g-C3 N4 are effectively modulated. The modified polymeric photocatalyst shows
      a high photocatalytic H2 evolution rate of 157.5 MUmol h-1 , a value that is 4.3
      times higher than the H2 evolution rate of pristine g-C3 N4 (36.8 MUmol h-1 ),
      with an apparent quantum efficiency of 9.7 % at lambda=450 nm. The incorporation
      of triamterene into the g-C3 N4 frameworks significantly expands its pi
      delocalized system by redistribution of the electronic potential, expands the
      visible-light absorption range, and effectively promotes the separation and
      migration of photoinduced charge carriers. This strategy may provide a reference
      for promoting charge separation of g-C3 N4 through redistribution of the
      electronic potential and for synthesizing novel carbon nitride based
      semiconductors for efficient solar energy conversion into hydrogen.

PMID- 30098234
TI  - Primary surgical treatment of nasal vestibule cancer - therapeutic outcome and
      reconstructive strategies.
AB  - OBJECTIVE: The treatment strategy of squamous cell carcinoma of the nasal
      vestibule (SCCNV) is controversial. The objective of this study is to investigate
      the role of surgery, which is the preferred treatment option at our institution.
      DESIGN: This was a monocentric prospective study of patients that were diagnosed
      with SCCNV between 2005 and 2013. MATERIAL AND METHODS: Twenty-six patients were
      included. Tumors were staged using the UICC (7th edition) TNM classification of
      nasal cavity cancer and the classification proposed by Wang. The primary
      treatment was surgery in all patients. Survival data were statistically analyzed
      using the Kaplan-Meier method. The median follow-up time was 6 years. RESULTS:
      Using the UICC classification, 9/26 tumors were staged as pT1 (35%), 7/26 as pT2
      (27%), and 10/26 as pT4a (39%). Using the classification by Wang, 9/26 tumors
      were staged as pT1 (35%), 15/26 as pT2 (58%), and 2/26 as pT3 (8%).
      Reconstruction was performed using an implant-retained prosthesis in 50% of
      patients and by plastic surgery in the remaining 50%. Only 2/26 patients (8%)
      needed adjuvant radiation therapy. The five-year recurrence-free survival (RFS)
      was 86.7%, disease-specific survival was 96.2% and overall survival was 91.8%
      after five years. CONCLUSION: Surgery in SCCNV gives an excellent prognosis and
      minimized the need for radiotherapy.

PMID- 30098235
TI  - [Screening for spinal muscular atrophy mutation carriers among 4931 pregnant
      women from Liuzhou region of Guangxi].
AB  - OBJECTIVE: To screen for carriers of SMN1 gene mutation, which underlies spinal
      muscular atrophy (SMA), in 4931 pregnant women from Liuzhou region of Guangxi,
      and to determine the carrier rate. METHODS: Combined denaturing high-performance
      liquid chromatography (DHPLC) and multiple PCR techniques were used to detect the
      copy number of SMN1 gene. The carrier frequency was calculated. The spouse of the
      carrier was also screened, and prenatal diagnosis was provided to the couples who
      were both positive. RESULTS: Among the 4931 pregnant women, 61 were found to
      harbor only one copy of the SMN1 gene, which yielded a carrier rate of 1.2%.
      Subsequent testing has identified 1 fetus carrying homozygous deletions of the
      SMN1 gene. CONCLUSION: The carrier rate of SMA mutation in Liuzhou region is
      slightly lower than that of other regions of southern China. DHPLC can
      effectively screen the carriers of SMA mutation and provide a basis for genetic
      counseling and prenatal diagnosis.

PMID- 30098236
TI  - [Analysis of MUT gene mutations and prenatal diagnosis for 20 pedigrees affected
      with isolated methylmalonic aciduria].
AB  - OBJECTIVE: To analyze MUT gene variants among 20 pedigrees affected with isolated
      methylmalonic aciduria by Sanger sequencing. METHODS: Peripheral blood samples
      were collected from the 20 probands and their parents. Following DNA extraction,
      the coding regions of the MUT gene were subjected to PCR amplification and Sanger
      sequencing. For 9 pedigrees, chorionic villus sampling was performed for prenatal
      genetic diagnosis. RESULTS: Nineteen variants were detected in the 20 pedigrees,
      with the most common ones including c.323G to A (p.Arg108His), c.1106G to A
      (p.Arg369His), c.729_730insTT(p.D244Lfs*39), and c.1107dupT (p.T370Yfs*22). Three
      variants were not reported previously, which included a small-scale deletion
      c.920_923delTCTT (p.F307Sfs*6) and two missense mutations c.419T to C
      (p.Leu140Pro) and 613G to A (p.Glu205Lys). For 9 pedigrees undergoing prenatal
      diagnosis, 1 fetus was normal, three were found to carry heterozygous mutations,
      while the remaining 5 fetuses have carried compound heterozygous mutations or
      homozygous mutations. CONCLUSION: Three novel variants of the MUT gene have been
      identified.

PMID- 30098237
TI  - [Analysis of SLC25A13 gene mutations and prenatal diagnosis for 20 families
      affected with citrin deficiency].
AB  - OBJECTIVE: To detect mutations of SLC25A13 gene in 20 families affected with
      citrin deficiency and provide prenatal diagnosis for them. METHODS: The 20
      probands and their parents were subjected to high-frequency mutation screening
      combined with Sanger sequencing. After confirming the genotype of each pedigree,
      genetic counseling and prenatal diagnosis were performed for their subsequent
      pregnancies. RESULTS: Biallelic pathogenic mutations of the SLC25A13 gene were
      identified in all probands. These included three deletions (c.851del4,
      c.1092_1095delT, and c.495delA), two splice-site mutations (IVS6+5G to A and
      IVS11+1G to A), two nonsense mutations (c.775C to T (p.Q259X) and c.72T to A
      (p.Y24X)), one duplication mutation (c.1638_1660dup), one insertion
      (IVSl6ins3kb), and one missense mutation (c.1775A to C (p.Q592P)). Among 24
      fetuses undergoing prenatal diagnosis, 8 had normal genotypes, 11 were mutation
      carriers, while 5 harbored biallelic mutations. Those with wild type alleles or
      heterozygous SLC25A13 mutations were delivered. Two fetuses harboring homozygous
      c.851del4 mutations were also delivered. Three fetuses harboring biallelic
      mutations were terminated. CONCLUSION: Analysis of SLC25A13 gene mutations in
      families affected by citrin deficiency can provide evidence for molecular
      diagnosis and facilitate genetic counseling and prenatal diagnosis for the
      subsequent pregnancy, which can effectively reduce the risk of birth of further
      affected children.

PMID- 30098238
TI  - [Analysis of NF1 gene mutations among eleven sporadic patients with
      neurofibromatosis type 1].
AB  - OBJECTIVE: To explore the genetic etiology for 11 sporadic patients with
      neurofibromatosis type 1. METHODS: Chip targeting capture and high-throughput
      sequencing were employed to detect potential mutations of NF1 and NF2 genes among
      the 11 patients. The data was filtered through multiple mutational databases and
      in-house whole exome sequence database. Sanger sequencing was used for analysis
      of family members of the patients. RESULTS: Eleven pathogenic variants were found
      among the 11 patients, which included two splicing mutations, one missense
      mutation, two nonsense mutations, and six frame-shifting mutations. None of the
      mutations was recorded by the public database or the in-house database generated
      from 1775 samples through whole exome sequencing. None of the unaffected parents
      carried the same mutation. Seven mutations were associated with neurofibromatosis
      type 1 previously, while the remaining four were discovered for the first time.
      Prenatal diagnosis of two high-risk pregnancies suggested that neither fetus has
      inherited the NF1 mutation from their affected parents. CONCLUSION:
      Identification of causative mutations in patients with sporadic-type
      neurofibromatosis type 1 has provided a basis for genetic counseling. The four
      novel mutations have enriched the spectrum of NF1 gene mutations.

PMID- 30098240
TI  - [Analysis of NF1 gene mutations in two sporadic patients with neurofibromatosis
      type 1].
AB  - OBJECTIVE: To detect mutations of the NF1 gene in two sporadic cases with
      neurofibromatosis type 1 (NF1) and explore their molecular mechanisms. METHODS:
      Clinical data of the two patients was collected. Genomic DNA was extracted from
      peripheral blood samples. Specific primers were designed to exclude pseudogenes.
      PCR was performed to amplify all coding exons of the NF1 gene. PCR products were
      directly sequenced. RESULTS: Two novel mutations of the NF1 gene (c.1019
      1020delCT in exon 9 and c.7189G to A in exon 48) were respectively identified in
      the two patients but not among their unaffected parents or 100 healthy controls.
      CONCLUSION: Mutations of the NF1 gene may have predisposed to the NF1 in the two
      patients.

PMID- 30098239
TI  - [Clinical and genetic features of five patients with Allan-Herndon-Dudley
      syndrome].
AB  - OBJECTIVE: To delineate the clinical and genetic characteristics of patients with
      Allan-Herndon-Dudley syndrome (AHDS). METHODS: Genetic testing was carried out by
      next generation sequencing on 117 patients featuring intellectual disability and
      developmental delay. Clinical information including clinical manifestation, brain
      magnetic resonance imaging(MRI), thyroid hormone levels, and electrocardiogram
      was collected for those with SLC16A2 mutations. RESULTS: Five male patients with
      SLC16A2 gene mutations were identified, including 2 affected brothers and 3
      sporadic cases. The ages of the patients ranged from 8 months to 8 years. All
      patients presented with severe intellectual disability and developmental delay
      including poor head control, inability to sit independently, no speech, and poor
      response to external stimuli. All patients presented with hypotonia, dystonia,
      and positive pyramidal signs. Three patients had sinus tachycardia. All patients
      had abnormal thyroid hormone levels with elevated free triiodothyronine (FT3),
      decreased free tetraiodothyronine(FT4), and normal thyroid stimulating hormone
      (TSH). Brain MRI on 3 patients showed delayed myelination. Among the 3 sporadic
      patients, 2 carried de novo mutations including c.61G to T(p.E21X) and
      c.695_699delATGGT(p.N232SfsX7), respectively, 1 carried a
      c.42delC(p.W15GfsX69)mutation, which was inherited from his heterozygous mother.
      A nonsense mutation (c.916C to T, p.Q306X) was discovered in the two brothers,
      for which their mother was heterozygous. CONCLUSION: AHDS is characterized by
      severe psychomotor developmental delay as well as congenital hypotonia, dystonia
      and positive pyramidal signs. Affected males may present with distinctive thyroid
      hormone abnormalities including increased FT3 and low FT4 accompanied by normal
      TSH. Delayed meylination of white matter is common. It is an X-linked mental
      retardation caused by SLC16A2 gene mutations.

PMID- 30098241
TI  - [Analysis of clinical manifestation and genetic mutations in two patients with
      Cornelia de Lange syndrome].
AB  - OBJECTIVE: To detect potential mutations in two neonates suspected for Cornelia
      de Lange syndrome (CdLS). METHODS: Peripheral blood samples from the neonates and
      their parents were collected and analyzed for CdLS-related genes using targeted
      sequence capture and next-generation sequencing. Suspected mutations were
      confirmed by direct Sanger sequencing. RESULTS: The neonates were found to
      respectively carry mutations c.7219C to T and p.D2339Lfs*4 of the NIPBL gene,
      among which the p.D2339Lfs*4 mutation has not been reported previously. No
      pathogenic mutation was found in other CdLS-related genes including NIPBL, SMC1A,
      SMC3, RAD21 and HDAC8. CONCLUSION: The c.7219C to T and p.D2339Lfs*4 mutations of
      the NIPBL gene probably account for the disease in both patients.

PMID- 30098242
TI  - [Analysis of DYSF gene mutations in two pedigrees affected with limb-girdle
      muscular dystrophy type 2B].
AB  - OBJECTIVE: To analyze mutations of DYSF gene in two pedigrees affected with limb
      girdle muscular dystrophy 2B (LGMD-2B). METHODS: Genomic DNA was extracted from
      peripheral blood samples of the two probands and unaffected family members.
      Variant sites were screened by next-generation sequencing using gene panel as
      well as Sanger sequencing. RESULTS: Four pathogenic mutations of the DYSF gene
      were detected, which included a de novo mutation and three mutations with
      uncertain significance. In pedigree 1, the proband carried compound heterozygous
      mutations of c.1667T to C (p.Leu556Pro) and c.5567T to A (p.Val1856Glu), which
      were respectively inherited from her mother and father. Proband of pedigree 2
      carried compound heterozygous mutations of c.4853A to G (p.Tyr1618Cys) and
      c.4876G to A (p.Val1612Ile), among which c.4876G to A (p.Val1626Ile) was also
      found in his father and grandfather, while c.4853A to G (p.Tyr1618Cys) was
      detected in his mother and grandmother. CONCLUSION: The two compound heterozygous
      mutations of the DYSF gene probably underlie the LGMD2B in the two pedigrees.
      Next generation sequencing has conferred great advantage for gene diagnosis of
      hereditary myopathy.

PMID- 30098243
TI  - [Clinical features and genetic analysis of seven patients with congenital
      hyperinsulinism].
AB  - OBJECTIVE: To analyze clinical characteristics, genetic mutation and therapeutic
      effect of seven patients diagnosed with congenital hyperinsulinism(CHI). METHODS:
      Clinical data for the patients was retrospectively analyzed. RESULTS: All
      patients presented with hyperinsulinism(serum insulin:2.0-58.4 mU/L),even after
      hypoglycemia (blood glucose: 0.7-2.39 mmol/L) has developed. Mutations were
      identified in 4 patients (57.1%), which included a heterozygous c.262C to
      T(p.R88C) mutation in exon 4 of the UCP2 gene, a heterozygous c.1495C to
      A(p.G499C) mutation in exon 12 of the GLUD1 gene, a heterozygous c.1493C to
      T(p.S498L) mutation in exon 1 of the GLUD1 gene, and a heterozygous c.4432G to
      A(p.G1478R) mutation in exon 37 of the ABCC8 gene. The patient carrying a
      maternally inherited ABCC8 mutation was treated with cornstarch and had his blood
      glucose kept normal. All other patients responded well to diazoxide. CONCLUSION:
      A genetic diagnosis was attained for 51.7% of patients in this study. Mild CHI
      patients can have their blood glucose controlled by giving cornstarch. Diazoxide
      is safe and effective for most CHI patients.

PMID- 30098244
TI  - [Identification of compound heterozygous mutations of SACS gene in two patients
      from a pedigree with spastic ataxia of Charlevoix-Saguenay].
AB  - OBJECTIVE: To detect potential mutations of the spastic ataxia of Charlevoix
      Saguenay (SACS) gene in a pedigree affected with autosomal recessive spastic
      ataxia of Charlevoix-Saguenay (ARSACS). METHODS: Genomic DNA was extracted from
      peripheral blood samples of the proband and her family members. All exons and
      flanking sequences of the SACS gene were analyzed by high-throughput sequencing.
      Suspected mutations were verified with Sanger sequencing. RESULTS: Next
      generation sequencing revealed novel compound heterozygous mutations of the SACS
      gene, namely c.13085T to G (p.I4362R) and c.5236dupA (p.T1746fs), in the proband,
      which were respectively derived from her parents. The mutations were confirmed by
      Sanger sequencing. CONCLUSION: The c.5236dupA (p.T1746fs) and c.13085T to G
      (p.I4362R) mutations of the SACS gene probably underlie the ocular symptoms and
      hearing loss in the proband.

PMID- 30098245
TI  - [Analysis of DSPP gene mutation in a Chinese pedigree affected with hereditary
      dentinogenesis imperfecta].
AB  - OBJECTIVE: To analyze the clinical phenotype of a Chinese pedigree affected with
      hereditary dentinogenesis imperfecta and mutation of dentin sialophosphoprotein
      (DSPP) gene. METHODS: Affected members underwent intraoral photography, dental
      film and panoramic radiography. Genomic DNA was extracted from peripheral venous
      blood samples. Coding regions of the DSPP gene were subjected to PCR
      amplification and Sanger sequencing. Functional effect of the mutation was
      predicted with SIFT and PolyPhen-2. The tertiary structure of wild type and
      mutant proteins were predicted by Swiss-Port. RESULTS: A heterozygous c.50C to T
      (p.P17L) mutation was identified in exon 2 of the DSPP gene in the proband and
      her father. The same mutation was not found among 200 unrelated healthy controls.
      The Pro-17 residues and its surrounding positions in DSPP are highly conserved
      across various species. The mutation was predicted to be damaging to the
      structure of DSPP protein. CONCLUSION: The c.50C to T (p.P17L) mutation of the
      DSPP gene probably underlies the disease in this pedigree. Above finding has
      expanded the spectrum of DSPP gene mutations and provided a basis for genetic
      counseling and prenatal diagnosis for this family.

PMID- 30098246
TI  - [Analysis of FOXL2 gene mutation and genotype-phenotype correlation in a Chinese
      pedigree affected with blepharophimosis-ptosis-epicanthus inversus syndrome].
AB  - OBJECTIVE: To detect FOXL2 gene mutation in a Chinese pedigree affected with
      blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type I, and to
      explore its genotype-phenotype correlation. METHODS: Peripheral blood samples
      were obtained from 3 patients and 19 healthy members from the pedigree for the
      isolation of genomic DNA. All exons and flanking sequences of the FOXL2 gene were
      amplified by PCR with 7 pairs of overlapping primers and sequenced. RESULTS: DNA
      sequencing indicated that the BPES phenotype in this pedigree was caused by a
      hotspot c.843_859dup17 mutation. The same mutation was not found among the
      healthy members of the pedigree. CONCLUSION: The c.843_859dup17 frameshift
      mutation probably underlies the BPES type I in this Chinese pedigree, which may
      manifest as either BEPS type I or type II.

PMID- 30098247
TI  - [Analysis of TGFBI gene mutation in a Chinese pedigree affected with lattice
      corneal dystrophy].
AB  - OBJECTIVE: To explore the clinical features and mutation of TGFBI gene in a
      Chinese pedigree affected with lattice corneal dystrophy (LCD). METHODS: Genomic
      DNA was extracted from 35 members including 11 patients from the pedigree. The 17
      exons and splicing region of introns of the TGFBI gene were amplified by PCR. The
      products were directly sequenced and compared with GenBank database to identify
      potential mutation. Bioinformatic analysis was carried out to predict the effect
      of mutation on proteins. RESULTS: A heterozygous mutation (p.R124C) was found in
      exon 4 of the TGFBI gene in all patients from the pedigree but not among
      unaffected members. The mode of inheritance of corneal dystrophy in this pedigree
      was identified as autosomal dominant. Bioinformatics analysis predicted that the
      p.R124C mutation may be functionally deleterious. The phenotype of corneal
      dystrophy in the pedigree was determined to be LCD I type. CONCLUSION: The
      p.R124C mutation of the TGFBI gene probably underlies the pathogenesis of LCD in
      this Chinese pedigree. Genetic testing can facilitate proper diagnosis of this
      type of corneal dystrophy.

PMID- 30098248
TI  - [Identification of compound heterozygous mutations p.Gly400Val and p.Arg532Ter of
      the F11 gene in a Chinese patient with hereditary factor XI deficiency].
AB  - OBJECTIVE: To investigate the phenotype and genotype defect characteristics of a
      Chinese patient with hereditary factor XI deficiency. METHODS: The activated
      partial thromboplastin time (APTT), prothrombin time (PT), FXI activity (FXI:C)
      of the proband and his relatives were measured by a clotting method using
      automatic coagulation analyzer. FXI antigen (FXI:Ag) was assayed by enzyme-linked
      immunosorbent assay (ELISA). Fifteen exons of the F11 gene were amplified by PCR
      and sequenced. Pymol software was used to analyze the novel mutations. RESULTS:
      The APTT of the proband was significantly prolonged (70.3 s, reference 34.5 s)
      with decreased FXI activity (6%, reference 50%-150%) and FXI antigen (1.9%,
      reference 50%-150%). The FXI activity and FXI antigen of his son was 31% and 39%,
      respectively. Two heterozygous F11 mutations were identified in the proband,
      which included a G to T substitution at nucleotide 1296 in exon 11 resulting in
      substitution of glycine by valine at codon 400 (p.Gly400Val) and a A to T
      substitution at nucleotide 1691 in exon 14 resulting in substitution of arginine
      (AGA) by a termination codon (TGA) at codon 532 (p.Arg532Ter). Analysis using
      Pymol indicated that the number of hydrogen bonds has changed, which led to a
      transformation of the structure of the FXI protein. The son of the proband was
      found to be heterozygous for the c.1296G to T (p.Gly400Val) mutation. NM_13142
      c.1691A to T (p.Arg532Ter) is a novel mutation based on HGMD professional 2016.4.
      Based on 2015 Guidelines of ACMG, it is PVS1 (very strong pathogenicity).
      CONCLUSION: The compound heterozygous mutations of F11 NM_13142 c.1296G to T
      (p.Gly400Val) and F11 NM_13142 c.1691A to T(p.Arg532Ter) probably underlies the
      FXI deficiency in the proband.

PMID- 30098249
TI  - [Analysis of clinical manifestation and genetic mutation in a child with X-linked
      chondrodysplasia punctata 2].
AB  - OBJECTIVE: To analyze clinical manifestations and genetic mutation in a child
      with severe short stature and other malformations. METHODS: The child has
      undergone history taking and physical examination. Genome DNA was extracted from
      peripheral blood samples of the proband and her family members. Candidate genes
      were captured with Agilent SureSelect and sequenced on an Illumina platform.
      Suspected mutation was verified by Sanger sequencing. RESULTS: The patient, a six
      year-and-10-month old girl, presented with non-symmetrical short stature,
      dysmorphism, abnormalities of limbs and spine, amblyopia of left eye, and
      cataract of right eye, in addition with frequent respiratory infection and
      micturition. Laboratory testing suggested 25-hydroxy vitamin D deficiency (18.9
      ng/mL). Spine X-ray showed multiple malformations with centrums. Her mother also
      featured short stature (138 cm). Her aunt had short stature (130 cm) and limb
      length discrepancy. Her little brother was 2.5 years old, and his height was 81
      cm (-3.4 SD). Exome sequencing revealed a heterozygous mutation c.184C to T
      (p.Arg62Trp) in the proband and her mother. The same mutation was not found in
      her father and brother. CONCLUSION: The patient was diagnosed with X-linked
      chondrodysplasia punctata 2. Mutation of the EBP gene probably underlied the
      disease in this family.

PMID- 30098250
TI  - [Genetic diagnosis of a child with aortic stenosis and thumb aplasia].
AB  - OBJECTIVE: To analyze the molecular mechanism and prognosis of a child with
      aortic stenosis and thumb aplasia. METHODS: The karotypes of the child and his
      parents were analyzed with routine G-banding. Their genomic DNA was also analyzed
      with array comparative genomic hybridization(aCGH) for chromosomal
      duplications/deletions. RESULTS: No karyotypic abnormality was detected at
      cytogenetic level for the child and his parents. aCGH identified a de novo 5.86
      Mb deletion at 2q22.3-q23.3 in the child. CONCLUSION: The child was diagnosed
      with 2q23.1 microdeletion syndrome. MBD5 may be the key gene for the 2q23.1
      microdeletion syndrome.

PMID- 30098251
TI  - [Phenotypic and genetic analysis of a boy with 3p26.3-pter deletion and 7q31.33
      qter duplication].
AB  - OBJECTIVE: To delineate the nature and origin of chromosomal copy number variants
      (CNVs) in a boy with mental retardation and multiple congenital malformation.
      METHODS: The karyotypes of the patient and his parents were analyzed with routine
      G-banded chromosomal analysis. Genome DNA was analyzed by next generation
      sequencing (NGS). RESULTS: The patient was found to harbor a structural
      aberration involving chromosome 3p. The karyotype of his father was
      46,XY,t(3;7)(p26;q31), while his mother was found to be normal. NGS analysis of
      the patient revealed a 2.16 Mb microdeletion at 3p26.3-pter and a duplication at
      7q31.33-qter. CONCLUSION: The structural aberration of 3p carried by the patient
      has derived from his father whom carried a balanced translocation of t(3;7), and
      his karyotype was finally determined as 46,XY,der(3) t(3;7)(p26.3;q31.33)pat. The
      abnormal phenotype of the patient can probably be attributed to the presence of
      3p26.3-pter microdeletion and 7q31.33-qter duplication.

PMID- 30098252
TI  - [Novel mutations of XPC gene detected in a family affected with xeroderma
      pigmentosum group C].
AB  - OBJECTIVE: To detect mutations of the XPC (XPC complex subunit, DNA damage
      recognition and repair factor) gene in a family affected with xeroderma
      pigmentosum group C (XP-C). METHODS: The patient was subjected to next-generation
      sequencing and Sanger sequencing. Suspected mutations were validated by Sanger
      sequencing. Effect of splicing mutation was confirmed by reverse transcription
      PCR (RT-PCR). RESULTS: Compound heterozygous mutations of c.2098G to T and c.2034
      7_2040del were found in the XPC gene in the proband. Among these, c.2098G to T
      (p.G700X) is a nonsense mutation resulting in a truncated XPC protein. C.2034
      7_2040del involves the -1 position, which may alter the splice donor site of the
      intron 11 of XPC and result in a truncated XPC protein with loss of amino acids
      from 940 to 679 positions. The two mutations were not detected among 100
      unrelated healthy controls. CONCLUSION: Mutations of c.2098 G to T and c.2034
      7_2040del of the XPC gene may lead to abnormal XPC expression and reduction or
      elimination of normal XPC functions, which may underlie the disease in this
      family.

PMID- 30098253
TI  - [Genotypic and phenotypic analysis of a case with inherited coagulation factor X
      deficiency].
AB  - OBJECTIVE: To explore the correlation between F10 gene mutation and its phenotype
      in a Chinese pedigree affected with FX deficiency. METHODS: Prothrombin time(PT),
      activated partial thromboplastin time(APTT), fibrinogen, FII activity(FII:C),
      FVII activity(FVII:C), FIX activity (FIX:C), FX activity(FX:C) were determined
      with a one-stage clotting assay. The FX antigen(FX:Ag) was detected with an
      enzyme linked immunosorbent assay(ELISA). The 8 exons, introns and 5' and 3'
      untranslated regions(UTR) of the F10 gene of the proband and her family members
      were subjected to PCR amplification and Sanger sequencing. Suspected mutation was
      confirmed by reverse sequencing. Polymorphisms were excluded by direct sequencing
      of 100 healthy individuals. RESULTS: The PT and APTT of the proband have
      prolonged to 16.1 s and 49.0 s, respectively. Her FX:C and FX:Ag were reduced by
      27% and 56%, and her mother's PT, APTT, FX:C and FX:Ag were 14.8 s, 37.4 s, 44%,
      34%, respectively. Her grandmother's PT, APTT, FX:C and FX:Ag were 15.8 s, 42.2
      s, 31%, 45%, respectively. The results of her father and other family members
      were all within the normal range. Genetic analysis has revealed a heterozygous G
      to A mutation in the proband at position 28076 in exon 8 of the F10 gene, which
      resulted in a p.Gly363Ser substitution. The same mutation was also found in her
      mother and grandmother. No mutation of the F10 gene was found in her father.
      Gly363Ser may result in changes in the secondary structure of the FX protein and
      reduction of its activity. CONCLUSION: The g.28076G to A(p.Gly363Ser) mutation of
      the F10 gene probably underlies the FX deficiency in this pedigree. The mutation
      was discovered for the first time in Chinese patients.

PMID- 30098254
TI  - [Analysis of a female neonate with pyruvate dehydrogenase complex deficiency].
AB  - OBJECTIVE: To analyze the clinical features and genetic basis of a female neonate
      with muscle weakness, abnormal brain magnetic resonance imaging and elevated
      blood lactate. METHODS: The patient was subjected to clinical and laboratory
      examination. Next generation sequencing was carried out for the patient and her
      relatives. RESULTS: The proband was diagnosed as small for gestational age, with
      clinical features including muscle weakness, abnormal brain magnetic resonance
      imaging, increased blood lactate, and acidosis. By genetic testing, a de novo
      PDHA1 mutation c.1133G to A (p.R378H) was identified, which was known to be
      pathogenic. The patient was diagnosed with pyruvate dehydrogenase complex
      deficiency disease (PDCDD), for which vitamin B1, coenzyme Q10, and L-carnitine
      were prescribed, and a ketogenic diet was recommended. Follow-up at 4-month-7-day
      found that her blood lactic acid was reduced to normal but her muscle tone was
      still low. CONCLUSION: The proband was diagnosed as PDCDD caused by a PDHA1
      missense mutation. NGS has provided a powerful tool for the diagnosis of such
      diseases.

PMID- 30098255
TI  - [Genetic and phenotypic analysis of a rare case with homozygous Chinese Ggamma
      (Agammadeltabeta)0-thal deletion].
AB  - OBJECTIVE: To analyze the genotype of a patient suspected for thalassemia through
      a series of experiments. METHODS: Conventional methods for detecting common
      thalassemia mutations was used in conjunction with multiplex ligation-dependent
      probe amplification (MLPA) in order to determine the genotype of the patient.
      Corresponding primers were designed for developing a Gap-PCR system for detecting
      rare type mutations. RESULTS: The patient was identified as a homozygote for
      Chinese Ggamma(Agammadeltabeta)0-thal deletion, with clinical manifestations
      tending to be intermediate or severe based on the hematological characteristics.
      A Gap-PCR system has been developed for detecting the above mutation with
      accuracy and rapidity. CONCLUSION: The Chinese Ggamma(Agammadeltabeta)0-thal is
      prevalent in southern China, and caution should be taken to avoid misdiagnosis.
      The Gap-PCR system for detecting Chinese Ggamma(Agammadeltabeta)0-thal is
      suitable for extended applications for its simplicity and rapidity.

PMID- 30098256
TI  - [Analysis of NIPBL gene mutation in a patient with Cornelia de Lange syndrome].
AB  - OBJECTIVE: To analyze the genotype-phenotype correlation in a case with Cornelia
      de Lange syndrome (CdLS). METHODS: Genetic testing was carried out for a baby
      girl born by Cesarean section. The patient had clinical features including
      peculiar face, long bushy eyebrows, hypertelorism, wide sagittal suture, low-set
      ears, retrognathia, polydactyly and polysyndactyly of first toes, weak cry, poor
      suck and slow response, and was suspected as CdLS. RESULTS: Sequencing of CdLS
      related genes including NIPBL, SMC1A, SMC3, RAD21 and HDAC8A has identified a
      novel heterozygous deletional mutation of the NIPBL gene. The deletion region has
      encompassed exon 46 and part of exon 47. The frameshift caused by the mutation
      has led to significant alteration of its protein sequence. CONCLUSION: A novel
      deletional mutation of the NIPBL gene has been identified, which has enriched its
      mutational spectrum and may facilitate further research into the genotype
      phenotype correlation of CdLS.

PMID- 30098257
TI  - [Association of single nucleotide polymorphisms of LEPR gene with essential
      hypertension among ethnic Mongolian and Han Chinese from Inner Mongolia region].
AB  - OBJECTIVE: To assess the association of single nucleotide polymorphisms (SNPs) of
      leptin receptor (LEPR) gene with essential hypertension (EH) and body mass index
      (BMI) among ethnic Mongolian and Han Chinese from Inner Mongolia region. METHODS:
      In total 411 Han Chinese patients with EH and 480 healthy controls, together with
      658 Mongolian patients with EH and 403 healthy controls, were collected. The SNPs
      of the LEPR gene were determined with ligase detection reaction (LDR). Logistic
      regression was used to analyze the association of the polymorphisms of each locus
      with EH and BMI. MDR software was used to analyze the interaction between above
      loci and environmental factors. RESULTS: Genotypic frequencies of LEPR gene
      rs7555955, rs1137100 and rs1137101 loci had differed significantly among ethnic
      Hans with EH and the control group (All P<0.05). While those of rs7555955,
      rs1805094, rs1137100, rs11579567, rs1805134 and rs6669354 loci had differed
      significantly among ethnic Mongolians with EH and the control group (All P<0.05).
      After adjustment for confounders, logistic regression analysis indicated that age
      (OR=2.97, 95%CI:1.94-3.99), BMI (OR=3.93, 95%CI:2.91-5.96), and rs1137101 (AA)
      (OR=3.96, 95%CI:1.32-11.90) were independent risk factors for EH among ethnic
      Hans, while age (OR=2.99, 95%CI:2.98-4.57), BMI (OR=3.03, 95%CI:1.05-1.27),
      rs7555955 (AG, AA) (OR=12.12, 95%CI:2.80-52.43; OR=6.35, 95%CI:1.44-27.94), and
      rs7555955 (GG) were independent risk factors for EH among ethnic Mongolians
      (P<0.05). CONCLUSION: Age and BMI are independent risk factors for EH in both
      ethnic Han and Mongolian Chinese. rs1137101 locus is associated with EH among
      ethnic Hans, while rs7555955 locus is associated with EH among ethnic Mongolians.

PMID- 30098258
TI  - [Association of TPH2 gene polymorphism with response to antidepressant treatment
      among ethnic Han Chinese population].
AB  - OBJECTIVE: To assess the association of TPH2 gene polymorphisms with the response
      or remission to selective serotonin reuptake inhibitors (SSRIs) drugs during
      treatment of major depressive disorder. METHODS: For 304 patients receiving SSRIs
      treatment for major depression disorder, 3 single nucleotide polymorphisms (SNPs)
      (rs1007023, rs1023990 and rs4570625) in the TPH2 gene were genotyped by MALDI-TOF
      mass spectrometry using a MassArray Analyzer 4 system. HAMD-17 was adopted as the
      primary rating tool to evaluate the severity of depression on the baseline and at
      the end of 1st, 2nd, 4th and 6th week of treatment. RESULTS: The frequency of GG
      genotype/G allele for rs4570625 differed significantly with the frequency of TT
      and GT genotypes/T allele between responders and non-responders (P=0.013 and
      0.007, respectively). Genotypic and allelic frequencies of the other
      polymorphisms did not differ significantly between the two groups (P>0.05). No
      association of TPH2 gene polymorphism with remission was found with the 3 SNPs.
      CONCLUSION: The polymorphisms of TPH2 gene may play an important role in response
      to antidepressant drug therapy.

PMID- 30098259
TI  - [Polymorphisms of methylenetetrahydrofolate reductase gene among women of
      childbearing age from Shiyan area].
AB  - OBJECTIVE: To assess the association of methylenetetrahydrofolate reductase
      (MTHFR) gene 677C to T polymorphism with blood homocysteine (Hcy) level among
      women of childbearing age from Shiyan area. METHODS: PCR-chip hybridization was
      used to determine the genotype of MTHFR 677C to T, and a biochemical assay was
      used to determine the total Hcy level among 428 healthy women of childbearing
      age. Association of MTHFR 677C to T with total Hcy level was assessed. RESULTS:
      Heterozygous CT mutation was most common form for the MTHFR 677C to T
      polymorphisms and amounted for 49.77% among the group, while the CC wild type and
      homozygous TT mutation respectively accounted for 30.61% and 19.63%. These gave a
      frequency of 44.51% for the 677T allele. The dominant genotype among different
      age groups were the CT type. Of note, the proportion of MTHFR 677CC is higher in
      women above 30 years of age. The distribution of MTHFR 677C to T genotypes has
      differed significantly among different age groups (P<0.05). Compared with those
      with wild type alleles, carriers of MTHFR mutations had a higher plasma Hcy
      level. The genotypic frequencies of MTHFR C677T in Shiyan region differed
      significantly from those of Sichuan, Hebei, Henan and Shandong (P<0.05) but were
      similar to those of Jiangsu, Guangdong, Ningxia and Xinjiang. CONCLUSION: The
      distribution of MTHFR C677T polymorphism among women of childbearing age in
      Shiyan area is influenced by age and is geographically specific and associated
      with plasma Hcy level. Nearly 50% of women have carried the high risk alleles,
      for whom folic acid supplementation is crucial for the reduction of birth defect
      rate.

PMID- 30098260
TI  - [Association of coagulation factor V gene polymorphism with unexplained recurrent
      spontaneous abortion among ethnic Hans from Wenzhou area].
AB  - OBJECTIVE: To assess the association of coagulation factor V gene polymorphisms
      with unexplained recurrent spontaneous abortion (URSA) among ethnic Han Chinese
      from Wenzhou area. METHODS: Ninety-six patients with URSA and 103 females with a
      history of normal pregnancy were recruited. Genotypes of coagulation factor V
      gene were determined through target sequence capture and high-throughput
      sequencing. The results were confirmed with a MassARRAY system. Allelic and
      genotypic frequencies between the two groups were compared. RESULTS: Nineteen
      single nucleotide polymorphism (SNPs), except coagulation factor V Leiden, were
      identified in the two groups. The frequencies of rs9287090 allele A, rs1046712
      allele T and rs1800594 allele G of the URSA group were lower than those of the
      control group (6.77% vs. 16.50%, 3.12% vs. 13.11%, 10.94% vs. 18.45%,
      respectively). After Bonferroni and false discovery rate correction, rs9287090
      and rs1046712 were significantly associated with URSA (corrected P<0.05).
      Although genotypic distribution of rs9287090 and rs1046712 also differed between
      the two groups, the corrected P value showed no significance (corrected P>0.05).
      A complete linkage disequilibrium (r2=1, D'=1) of rs6022 and rs6029 was observed
      for the haplotype block rs6022-rs6029-rs6028. The frequencies of rs6022 allele A
      and rs6029 allele T were higher in the URSA group with corrected insignificance
      (75.00% vs. 65.53%, corrected P>0.05). Furthermore, significantly more A-T-T
      haplotype was found in the URSA group (75.00% vs. 65.50%, OR=1.578, 95%CI:1.021
      2.438, chi2=4.248, P<0.05). CONCLUSION: The decreased rate of rs9287090 allele A,
      rs1046712 allele T, and rs1800594 allele G may contribute to the susceptibility
      to URSA among ethnic Han Chinese from Wenzhou area. The rs6022 allele A and
      rs6029 allele T may also predispose to URSA.

PMID- 30098261
TI  - [Association of vascular endothelial growth factor gene polymorphisms with
      Crohn's disease among Chinese patients].
AB  - OBJECTIVE: To assess the association of vascular endothelial growth factor (VEGF)
      gene polymorphisms with susceptibility to Crohn's disease (CD) in a Chinese
      population. METHODS: For 275 CD patients and 495 controls, the genotypes of VEGF
      gene rs699947 and rs3025039 loci were determined with a SNaPshot method. RESULTS:
      The allelic and genotypic frequencies of the rs699947 and rs3025039 loci did not
      differ between the two groups (all P>0.05). By stratification analysis, allele A
      and genotype CA+AA of rs699947 were more frequent in patients with colonic CD
      compared with the controls (P=0.006, 95%CI:1.143-2.234; P=0.005, 95%CI:1.203
      2.900, respectively). Compared with the controls, the allele A and genotype CA+AA
      of rs699947 were less frequent in patients with ileal lesions including ileal CD
      and ileocolonic CD (P=0.033, 95%CI:0.524-0.974;P=0.043, 95%CI:0.481-0.989,
      respectively). The frequency of TT homozygote of rs3025039 was lower in patients
      with non-stricturing and non-penetrating CD compared with the controls (P=0.036,
      95%CI:0.016-0.870). CONCLUSION: Polymorphisms of the VEGF gene rs699947 locus may
      contribute to an increased risk for colonic CD, but may play a protective role in
      patients with ileal lesion. Individuals carrying the TT genotype for VEGF
      rs3025039 locus may be less susceptible to non-stricturing and non-penetrating
      CD.

PMID- 30098262
TI  - [Association of GPER gene polymorphism with social function of children with
      attention deficit hyperactivity disorder].
AB  - OBJECTIVE: To assess the association of G protein-coupled estrogen receptor(GPER)
      gene polymorphism with social function of children with attention deficit
      hyperactivity disorder (ADHD). METHODS: The social function of 135 children with
      ADHD were assessed by Weiss Functional Impairment Scale-Parent form (WFIRS-P).
      The coding region of GPER gene of all patients was subjected to Sanger
      sequencing. The association of polymorphisms with the social function of the ADHD
      children was analyzed. RESULTS: In the case group, the social function scores of
      Learning and School and Risky Activities of boys were significantly higher than
      those of girls (t=2.704, P=0.008; t=2.289, P=0.027). No significant difference
      was found in the genotypic frequencies of the c.-9T/C and c.789G/A loci between
      different genders. But the learning and school scores of those with a TC genotype
      for the c.-9T to C locus were significantly higher than those with a TT genotype
      (t= 2.159, P=0.033). CONCLUSION: For children with ADHD, the social function of
      Learning and School of those with a TC genotype of the GPER gene c.-9T/C locus is
      more severely damaged compared with those with a TT genotype.

PMID- 30098263
TI  - [Application of next generation sequencing for the detection of chromosomal
      aneuploidies and copy number variations in abortus tissues].
AB  - OBJECTIVE: To detect numerical chromosomal aberrations and copy number variations
      (CNVs) in abortus tissue samples with a benchtop semiconductor sequencing
      platform (SSP). METHODS: One hundred and forty patients with early spontaneous
      abortions at between 7 and 16 weeks were selected. Following DNA extraction,
      library preparation, high-throughput sequencing was carried out. RESULTS:
      Chromosomal anomalies were detected in 82 cases (58.57%), which included 67
      aneuploidies and 15 CNVs. Trisomies 16, 21, 22, and X/Y were the most common. A
      significant difference was found in the anomaly rates between women <35 and >=35
      years old (P< 0.01). CONCLUSION: The SSP platform can detect chromosomal
      aneuploidies and CNVs among abortus tissues. Numerical chromosomal aberration is
      the main cause of early spontaneous abortion, and advance maternal age is a high
      risk factor for chromosomal abnormality.

PMID- 30098264
TI  - [Genetic polymorphism and relationship of 24 Y-STR loci among three ethnic
      minorities from Guizhou].
AB  - OBJECTIVE: To study the distribution of haplotypes of Y-chromosomal short tandem
      repeats (Y-STR) loci among three ethnic minorities from Guizhou, China. METHODS:
      Twenty four Y-STR loci of 174 unrelated males were amplified with a
      Microreader(TM)24Y Direct ID System kit. Capillary electrophoresis was carried
      out on an ABI 3100 Genetic Analyzer, and the data was analyzed with GeneMapper
      software. RESULTS: Seventy six haplotypes were identified for the 24 Y-STR loci
      among the three ethnic minorities, including 13 from the Qiangs, 35 from the
      Manchurians, and 28 from the Shes, with the corresponding Haplotype Diversity
      (HD) being 0.7327, 0.9578, and 0.9344. Genetic distance between the Shes and
      Qiangs was relatively close, whilst that for Manchurians was relatively far.
      CONCLUSION: Analysis of the genetic characteristics and relationship of the three
      ethnic minorities from Guizhou can provide a reference for the study of their
      origin, evolution and patrilineal fusion.

PMID- 30098265
TI  - [Progress in genetic research on primary pulmonary hypertension].
AB  - Primary pulmonary hypertension (PPH) consisting of hereditary pulmonary arterial
      hypertension and idiopathic pulmonary arterial hypertension is an obstructive
      pulmonary hypertension caused by primary pulmonary artery hyperplasia. Both
      environmental and genetic factors are involved in the pathogenesis of PPH. Genes
      associated with TGF-beta signaling pathway including BMPR2, ALK1, ENG, SMAD8 and
      other genes including NFU1, CAV1, KCNK3 and TopBPl have been associated with PPH.
      In this review, the function and mechanism of the above genes in the pathogenesis
      PPH are summarized.

PMID- 30098266
TI  - [Congenital cataract in a pedigree with six cases].

PMID- 30098267
TI  - The Twist of the Achilles Tendon - Associations of Torsions in the Lower
      Extremity.
AB  - Achilles tendinopathy and rupture of the Achilles tendon (AT) are frequent
      pathologies. Even though they may be associated with the twisted morphology of
      the AT, quantitative data on the extent of the twist of the entire AT are not
      available. The aim of this study was to investigate the torsion of the AT based
      on its individual parts and to evaluate a possible correlation with the torsion
      of the long bones of the lower extremity. Forty embalmed lower extremities were
      included in this study. The lateral deviation of the AT and its torsional angle
      as well as the angles of the individual parts in trans-section were measured.
      Thereafter, the torsions of femur and tibia were evaluated. Measuring the lateral
      deviation of the fibers resulted in an average torsion of the AT of 34.59 degrees
      (SD 16.8 degrees ). The angles of the different parts of the AT in trans-section
      resulted in a median AT torsion of 15.73 degrees , showing various patterns of
      rotations of the individual muscles. A statistically significant correlation
      between the torsions of the lower extremity and the AT (P =0.0242, r = 0.40) as
      well as a correlation between the femoral torsion and the AT torsion (P = 0.0127,
      r = 0.44) were found. This study adds to the morphological understanding of the
      torsion of the AT and its correlation with the torsions of the long bones of the
      lower extremity. Especially, the torsion of the femur seems to be connected to
      the torsion of the tendon. Clin. Anat. 31:1085-1091, 2018. (c) 2018 The Authors.
      Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of American
      Association of Clinical Anatomists.

PMID- 30098268
TI  - Do you know when a wound has healed? Insights from a large-scale multinational
      consumer survey.

PMID- 30098270
TI  - Complex mixture quantification without calibration using gas chromatography and a
      comprehensive carbon reactor in conjunction with flame ionization detection.
AB  - Quantification of complex carbon-containing mixtures is typically a very time
      intensive task with regards to the calibration process. A gas chromatograph with
      a flame ionization detector yields strong responses to organic compounds and
      provides a wide linear range over many orders of magnitude; however, responses
      for highly functionalized and heteroatom-containing compounds can be variable.
      Here, a commercial Polyarc microreactor unit, placed before the flame ionization
      detector, was investigated as a means of normalizing carbon response across all
      compounds. The device includes two catalytic reaction chambers, ultimately
      converting all carbon atoms to methane evenly for flame ionization detection.
      Three groups of different complex mixtures from n-alkane to terpene and polymer
      mixtures were analyzed to evaluate the potential for calibration-free
      quantitation of the new detector arrangement. We have obtained accurate
      quantification results without time-consuming calibration processes. The
      quantification of a terpene mixture and a polymer mixture confirms the ability of
      the detector for analyzing samples that either have complex physical or
      structural properties or wide concentration range. In summary, compared to other
      detectors, this methanizer - flame ionization detection system provides a
      simplified workflow, which can eliminate calibration steps and increase
      throughput.

PMID- 30098269
TI  - Low-fat versus ketogenic diet in Parkinson's disease: A pilot randomized
      controlled trial.
AB  - BACKGROUND: Preliminary evidence suggests that diet manipulation may influence
      motor and nonmotor symptoms in PD, but conflict exists regarding the ideal fat to
      carbohydrate ratio. OBJECTIVES: We designed a pilot randomized, controlled trial
      to compare the plausibility, safety, and efficacy of a low-fat, high-carbohydrate
      diet versus a ketogenic diet in a hospital clinic of PD patients. METHODS: We
      developed a protocol to support PD patients in a diet study and randomly assigned
      patients to a low-fat or ketogenic diet. Primary outcomes were within- and
      between-group changes in MDS-UPDRS Parts 1 to 4 over 8 weeks. RESULTS: We
      randomized 47 patients, of which 44 commenced the diets and 38 completed the
      study (86% completion rate for patients commencing the diets). The ketogenic diet
      group maintained physiological ketosis. Both groups significantly decreased their
      MDS-UPDRS scores, but the ketogenic group decreased more in Part 1 (-4.58 +/-
      2.17 points, representing a 41% improvement in baseline Part 1 scores) compared
      to the low-fat group (-0.99 +/- 3.63 points, representing an 11% improvement) (P
      < 0.001), with the largest between-group decreases observed for urinary problems,
      pain and other sensations, fatigue, daytime sleepiness, and cognitive impairment.
      There were no between-group differences in the magnitude of decrease for Parts 2
      to 4. The most common adverse effects were excessive hunger in the low-fat group
      and intermittent exacerbation of the PD tremor and/or rigidity in the ketogenic
      group. CONCLUSIONS: It is plausible and safe for PD patients to maintain a low
      fat or ketogenic diet for 8 weeks. Both diet groups significantly improved in
      motor and nonmotor symptoms; however, the ketogenic group showed greater
      improvements in nonmotor symptoms. (c) 2018 The Authors. Movement Disorders
      published by Wiley Periodicals, Inc. on behalf of International Parkinson and
      Movement Disorder Society.

PMID- 30098271
TI  - Effects of novel brominated flame retardant TBBPA on human airway epithelial cell
      (A549) in vitro and proteome profiling.
AB  - The cellular toxicity response of human airway epithelial cells (A549) to
      tetrabromobisphenol (TBBPA) was assessed in vitro. Cell viability, levels of
      intracellular reactive oxygen species (ROS), lipid peroxidation (MDA), and
      caspase-3 activity were determined after A549 treated with varying concentrations
      of TBBPA. A comparative proteomic analysis was performed in cells treated with
      different concentrations of TBBPA (0, 10, and 40 MUg/mL). Two-way anova analysis
      showed that cell viability was significantly decreased after treatment by TBBPA
      with a concentration of 16 MUg/mL for 48 hr, however, the caspase-3 activities,
      ROS generation, and MDA content increased. Ultrastructural observation revealed
      that the cell was morphological damaged after exposure to 64 MUg/mL TBBPA, with
      mitochondria seriously injured and the smooth endoplasmic reticulum dilated.
      There was a good correlation between ROS generation and mitochondrial
      dysfunction. Seventeen differentially expressed proteins involved in various
      biological processes were identified. These findings provide a basis for
      understanding the mechanisms of cell dysfunction and perturbation of antioxidant
      status induced by additive flame retardant on airway epithelial cells.

PMID- 30098272
TI  - A multicenter, randomized, single-blind trial comparing the efficacy of viable
      cryopreserved placental membrane to human fibroblast-derived dermal substitute
      for the treatment of chronic diabetic foot ulcers.
AB  - Randomized controlled clinical trials, the gold standard to determine treatment
      efficacy against control, have demonstrated advantages of skin substitutes for
      the treatment of chronic diabetic foot ulcers in comparison to standard of care.
      However, randomized controlled clinical trials comparing efficacy between two or
      more skin substitutes are very limited. With growing numbers of new skin
      substitutes, such studies are essential for treatment and policy-making decisions
      by wound care providers and payers. In this study, we analyzed clinical outcomes
      and product cost between a viable cryopreserved placental membrane (vCPM) and a
      human fibroblast-derived dermal substitute (hFDS) for the treatment of chronic
      diabetic foot ulcers in a prospective, multicenter, single-blind study. The
      outcomes of 62 patients were analyzed: 31 patients in the vCPM treatment group
      and 31 patients in the hFDS treatment group. Utilizing a non-inferiority trial
      design and the established treatment regimen of 8 applications for hFDS, we
      demonstrated that vCPM was not inferior to hFDS for the proportion of patients
      achieving complete wound closure (9.68, 90% CI: [10.67, 28.94]). However,
      preliminary findings show that vCPM may have better outcomes for wounds <= 5 cm2
      : 81.3% (13/16) of wounds in the vCPM group vs. 37.5% (6/16) of wounds in the
      hFDS group reached complete closure at the end of treatment (p = 0.0118). A
      preliminary product cost analysis for wounds <= 5 cm2 may show significant
      savings for patients treated with vCPM. Average per-patient costs during the
      course of treatment were $3,846 and $7,968 (p < 0.0001) for vCPM and hFDS
      patients, respectively. These results may be used as guidance to wound care
      providers and payers.

PMID- 30098275
TI  - Hydrogenation of Inorganic Metal Carbonates: A Review on Its Potential for Carbon
      Dioxide Utilization and Emission Reduction.
AB  - Carbonaceous minerals represent a valuable and abundant resource. Their
      exploitation is based on decarboxylation at elevated temperature and under
      oxidizing conditions, which inevitably release carbon dioxide into the
      atmosphere. Hydrogenation of inorganic metal carbonates opens up a new pathway
      for processing several metal carbonates. Preliminary experimental studies
      revealed significant advantages over conventional isolation technologies. Under a
      reducing hydrogen atmosphere, the temperature of decarboxylation is significantly
      lower. Carbon dioxide is not directly released into the atmosphere, but may be
      reduced to carbon monoxide, methane, and higher hydrocarbons, which adds value to
      the overall process. Apart from metal oxides in different oxidation states,
      metals in their elemental form may also be obtained if transition-metal
      carbonates are processed under a hydrogen atmosphere. This review summarizes the
      most important findings and fields of the application of metal carbonate
      hydrogenation to elucidate the need for a detailed investigation into optimized
      process conditions for large-scale applications.

PMID- 30098273
TI  - Glucose suppresses IL-1beta-induced MMP-1 expression through the FAK, MEK, ERK,
      and AP-1 signaling pathways.
AB  - Osteoarthritis (OA) commonly affects the synovial joint and is characterized by
      degradation of articular cartilage. Increased matrix metalloproteinase (MMP)
      activity plays a major role in this degradation. Dextrose (D-glucose)
      prolotherapy has shown promising activity in the treatment of different
      musculoskeletal disorders, including OA. However, little is known about the role
      of glucose on MMP inhibition in OA therapy. We found that stimulating
      chondrocytes with the proinflammatory cytokine interleukin-1beta (IL-1beta)
      increased the expression of MMP-1, MMP-3, and MMP-13. Glucose reduced this
      increase in MMP-1 expression, but had no effect upon MMP-3 or MMP-13 expression.
      Analyses using a focal adhesion kinase (FAK) inhibitor, MEK inhibitors (U0126 and
      PD98059), an ERK inhibitor, AP-1 inhibitors (curcumin and tanshinone), or siRNAs
      demonstrated that the FAK, MEK, ERK, and AP-1 pathways mediate IL-1beta-induced
      increases in MMP-1 expression. Glucose antagonized IL-1beta-promoted
      phosphorylation of FAK, MEK, ERK, and c-Jun. Thus, glucose decreased IL-1beta
      induced MMP-1 expression through the FAK, MEK, ERK, and AP-1 signaling cascades.
      These findings may provide a better understanding of the mechanisms of
      prolotherapy on inhibiting MMP expression.

PMID- 30098276
TI  - Hippocampal brain-derived neurotrophic factor determines recruitment of
      anatomically connected networks after stress in diabetic mice.
AB  - Diabetes increases adrenal steroids in humans and animal models, but potential
      interactions with psychological stress remain poorly understood. Diabetic rodents
      exhibit anxiety and reductions in hippocampal brain-derived neurotrophic factor
      (BDNF) expression, and these studies investigated whether loss of BDNF-driven
      hippocampal activity promotes anxiety and disinhibits the HPA axis. Mice with
      genetic obesity and diabetes (db/db) received intrahippocampal injections of
      lentivirus for BDNF overexpression (db/db-BDNFOE), and Wt mice received
      lentiviral constructs for BDNF knockdown (Wt-BDNFKD). Behavioral anxiety and
      glucocorticoid responses to acute restraint were compared with mice that received
      a fluorescent reporter (Wt-GFP, db/db-GFP). These experiments revealed that
      changes in hippocampal BDNF were necessary and sufficient for behavioral anxiety
      and HPA axis disinhibition. To examine patterns of stress-induced regional
      activity, we used algorithmic detection of cFos and automated segmentation of
      forebrain regions to generate maps of functional covariance, which were
      subsequently aligned with anatomical connectivity weights from the Brain
      Architecture Management database. db/db-GFP mice exhibited reduced activation of
      the hippocampal ventral subiculum (vSub) and anterior bed nucleus of stria
      terminalis (aBNST), and increases in the paraventricular hypothalamus (PVH),
      relative to Wt-GFP. BDNFKD recapitulated this pattern in Wt mice, and BDNFOE
      normalized activation of the vSub > aBNST > PVH pathway in db/db mice. Analysis
      of forebrain activation revealed largely overlapping patterns of network
      disruption in db/db-GFP and Wt-BDNFKD mice, implicating BDNF-driven hippocampal
      activity as a determinant of stress vulnerability in both the intact and diabetic
      brain.

PMID- 30098274
TI  - In vitro evaluation of the toxicity and underlying molecular mechanisms of Janus
      Fe3 O4 -TiO2 nanoparticles in human liver cells.
AB  - Recent studies show that Janus Fe3 O4 -TiO2 nanoparticles (NPs) have potential
      applications as a multifunctional agent of magnetic resonance imaging (MRI) and
      photodynamic therapy (PDT) for the diagnosis and therapy of cancer. However,
      little work has been done on their biological effects. To evaluate the toxicity
      and underlying molecular mechanisms of Janus Fe3 O4 -TiO2 nanoparticles, an in
      vitro study using a human liver cell line HL-7702 cells was conducted. For
      comparison, the Janus Fe3 O4 -TiO2 NPs parent material TiO2 NPs was also
      evaluated. Results showed that both Fe3 O4 -TiO2 NPs and TiO2 NPs decreased cell
      viability and ATP levels when applied in treatment, but increased malonaldehyde
      (MDA) and reactive oxygen species (ROS) generation. Mitochondria JC-1 staining
      assay showed that mitochondrial membrane permeability injury occurred in both NPs
      treated cells. Cell viability analysis showed that TiO2 NPs induced slightly
      higher cytotoxicity than Fe3 O4 -TiO2 NPs in HL7702 cells. Western blotting
      indicated that both TiO2 NPs and Fe3 O4 -TiO2 NPs could induce apoptosis,
      inflammation, and carcinogenesis related signal protein alterations.
      Comparatively, Fe3 O4 -TiO2 NPs induced higher signal protein expressions than
      TiO2 NPs under a high treatment dose. However, under a low dose (6.25 MUg/cm2 ),
      neither NPs had any significant toxicity on HL7702 cells. In addition, our
      results suggest both Fe3 O4 -TiO2 NPs and TiO2 NPs could induce oxidative stress
      and have a potential carcinogenetic effect in vitro. Further studies are needed
      to elaborate the detailed mechanisms of toxicity induced by a high dose of Fe3 O4
      -TiO2 NPs.

PMID- 30098278
TI  - Authors' reply re: Randomised controlled trial to estimate reduction in pain
      after laparoscopic surgery when using a combination therapy of intraperitoneal
      normal saline and the pulmonary recruitment manoeuvre.

PMID- 30098277
TI  - Supramolecular Metallopolymers: From Linear Materials to Infinite Networks.
AB  - The fields of coordination polymers (CPs) and supramolecular metallopolymers
      (SMPs) have been extensively studied for decades. Spectacular recent advances in
      both fields have created new compounds that lie at the interface between these
      two classes of organic-inorganic hybrid materials. At this interface, materials
      based on molecular weaving, supramolecular clusters, and metal-organic framework
      polymer hybrids have emerged. This minireview provides a perspective on the
      intellectual emergence and connection between different supramolecular constructs
      and the state of the art with respect to this new materials interface.

PMID- 30098279
TI  - Anti-carcinogenic effect of hesperidin against renal cell carcinoma by targeting
      COX-2/PGE2 pathway in Wistar rats.
AB  - The present study was designed to evaluate the protective effects of hesperidin,
      a flavonoid on DEN initiated and Fe-NTA promoted renal carcinogenesis in Wistar
      rats. Renal cancer was initiated by a single i.p. injection of DEN (200 mg/kg
      b.wt.) and promoted with Fe-NTA (9 mg Fe/kg b.wt. i.p.) twice a week for 16
      weeks. Rats were simultaneously administered with hesperidin (100 and 200 mg/kg
      b.wt.) for 16 consecutive weeks. The chemopreventive effect of hesperidin was
      assessed in terms of antioxidant activities, renal function, PGE2 level, and the
      expressions of COX-2 and VEGF. Hesperidin decreased the DEN and Fe-NTA induced
      lipid peroxidation, improved the renal function (by decreasing the levels of BUN,
      creatinine, and KIM-1) and restored the renal antioxidant armory (GSH, GPx, GR,
      SOD, and catalase). Hesperidin was also found to decrease the level of PGE2 and
      downregulate the expressions of COX-2 and VEGF. Histological findings further
      revealed the protective effects of hesperidin against DEN and Fe-NTA induced
      kidney damage. The result of our present findings suggest that hesperidin may be
      a promising modulator in preventing renal cancer possibly by virtue of its
      ability to alleviate oxidative stress and inhibit COX-2/PGE2 pathway.

PMID- 30098281
TI  - Distribution of CYP2D6 genotypes in the Indian population - preliminary report.

PMID- 30098280
TI  - Staphylococcal superantigen-like protein 13 activates neutrophils via formyl
      peptide receptor 2.
AB  - Staphylococcal superantigen-like (SSL) proteins, one of the major virulence
      factor families produced by Staphylococcus aureus, were previously demonstrated
      to be immune evasion molecules that interfere with a variety of innate immune
      defences. However, in contrast to characterised SSLs, which inhibit immune
      functions, we show that SSL13 is a strong activator of neutrophils via the formyl
      peptide receptor 2 (FPR2). Moreover, our data show that SSL13 acts as a
      chemoattractant and induces degranulation and oxidative burst in neutrophils. As
      with many other staphylococcal immune evasion proteins, SSL13 shows a high degree
      of human specificity. SSL13 is not able to efficiently activate mouse
      neutrophils, hampering in vivo experiments. In conclusion, SSL13 is a neutrophil
      chemoattractant and activator that acts via FPR2. Therefore, SSL13 is a unique
      SSL member that does not belong to the immune evasion class but is a pathogen
      alarming molecule. Our study provides a new concept of SSLs; SSLs not only
      inhibit host immune processes but also recruit human neutrophils to the site of
      infection. This new insight allows us to better understand complex interactions
      between host and S. aureus pathological processes.

PMID- 30098282
TI  - Simvastatin-related myopathy in shift workers: a report of two cases.

PMID- 30098283
TI  - Reciprocal role of hBD2 and hBD3 on the adaptive immune response by measuring T
      lymphocyte proliferation in terms of CD4 and CCR6 expression.
AB  - Background Human beta-defensins (hBD2 and hBD3) are small cationic antimicrobial
      peptides of innate immune system which can act as a barrier against the majority
      of pathogens, contributing to the host immune defence. Objective The aim of study
      is to determine whether hBD2 and hBD3 play a role in development and
      proliferation of human effector CD4 T cells or not. Furthermore, if enhanced
      proliferation is observed in the presence of hBD2 and hBD3, these data will
      demonstrate whether chemokine receptor type 6 (CCR6) is required to be present
      for this activity to occur. Methods In this study, we examined the effect of hBD2
      and hBD3 on CD4+ T cell proliferation in CCR6+ and CCR6- T cells through co
      culture of peripheral blood mononuclear cells with anti-CD3 and anti-CD28
      stimulation in the presence or absence of hBD2 and hBD3. Proliferation was
      assessed using flow cytometry. Results It was demonstrated that, co-culture with
      hBD2 and hBD3 led to up-regulation of CD4+ T cell proliferation after 72 h
      whereas, CD4+ T cell proliferation was suppressed after 96 h. On the other hand,
      CCR6- and CCR6+ T cell proliferation was up-regulated after 72 h. But, CCR6+ only
      was down-regulated in the second cycle in the presence of hBD3. In contrast,
      after 96 h CCR6+ and CCR6- T cell proliferation was decreased. Conclusion
      Collectively, our data indicated that hBD2 and hBD3 play a positive and negative
      regulatory role in development and proliferation of human effector CD4+ T cells
      which is essential for optimal adaptive immune responses and the control of
      immunopathology.

PMID- 30098284
TI  - Studying non-alcoholic fatty liver disease: the ins and outs of in vivo, ex vivo
      and in vitro human models.
AB  - The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing.
      Determining the pathogenesis and pathophysiology of human NAFLD will allow for
      evidence-based prevention strategies, and more targeted mechanistic
      investigations. Various in vivo, ex situ and in vitro models may be utilised to
      study NAFLD; but all come with their own specific caveats. Here, we review the
      human-based models and discuss their advantages and limitations in regards to
      studying the development and progression of NAFLD. Overall, in vivo whole-body
      human studies are advantageous in that they allow for investigation within the
      physiological setting, however, limited accessibility to the liver makes direct
      investigations challenging. Non-invasive imaging techniques are able to somewhat
      overcome this challenge, whilst the use of stable-isotope tracers enables
      mechanistic insight to be obtained. Recent technological advances (i.e.
      normothermic machine perfusion) have opened new opportunities to investigate
      whole-organ metabolism, thus ex situ livers can be investigated directly.
      Therefore, investigations that cannot be performed in vivo in humans have the
      potential to be undertaken. In vitro models offer the ability to perform
      investigations at a cellular level, aiding in elucidating the molecular
      mechanisms of NAFLD. However, a number of current models do not closely resemble
      the human condition and work is ongoing to optimise culturing parameters in order
      to recapitulate this. In summary, no single model currently provides insight into
      the development, pathophysiology and progression across the NAFLD spectrum, each
      experimental model has limitations, which need to be taken into consideration to
      ensure appropriate conclusions and extrapolation of findings are made.

PMID- 30098285
TI  - The diagnostic challenge of ovarian carcinoma in normal-sized ovaries: a report
      of two cases.
AB  - Normal-sized ovarian carcinoma syndrome (NOCS) is a rare condition characterised
      by malignancy identified in ovaries of normal size with abdominal metastasis. We
      report two cases of advanced ovarian carcinoma with ovaries of normal size. The
      first case was a 13-year-old adolescent with malignant ascites and bilateral
      normal sized multicystic ovaries detected on ultrasound. Serum cancer antigen 125
      (CA 125) and lactate dehydrogenase were markedly raised. A computed tomography
      (CT) scan showed the presence of thick omental cake but no ovarian tumour. An
      ultrasound-guided biopsy of the omental cake was undertaken. A histopathological
      examination and immunohistochemical studies of omentum caking confirmed a
      diagnosis of high-grade serous carcinoma of ovarian in origin. Despite
      neoadjuvant chemotherapy, she deteriorated rapidly with acute renal failure and
      respiratory distress. She succumbed to her disease 10 weeks after diagnosis. The
      second case, a 69-year-old postmenopausal female presented with malignant ascites
      and ultrasound evaluation showed hydrometra and bilateral atrophic ovaries. CA
      125 was significantly raised. A laparoscopic biopsy of the left ovary and
      endometrial sampling were performed. A diagnosis of synchronous primary high
      grade papillary serous ovarian cystadenocarcinoma and endometrial adenocarcinoma
      were revealed. Relapse occurred despite ongoing adjuvant chemotherapy. We
      concluded that a preoperative definitive diagnosis of NOCS is difficult. Strong
      clinical suspicion is needed when all the important causes of malignant ascites
      are excluded. Radiological-guided biopsy and laparoscopic biopsy are useful to
      achieve the diagnosis of NOCS.

PMID- 30098286
TI  - A personal series of 100 children operated for Cushing's disease (CD): optimizing
      minimally invasive diagnosis and transnasal surgery to achieve nearly 100%
      remission including reoperations.
AB  - Background Transnasal surgery (TNS) is the first choice in the treatment of
      pediatric Cushing's disease. The question is how can high remission rates be
      achieved with minimally invasive investigations and TNS whilst avoiding
      radiotherapy or bilateral adrenalectomy in children. Methods Data from a
      published series 1 (n=55) of surgeon DKL will be compared with his recent series
      2 (n=45) until 2009. All patients were operated by direct transnasal
      microsurgery. Over time, inferior petrosal sinus sampling (IPSS) was replaced by
      cavernous sinus sampling (CSS), restricted to unclear cases without increase of
      salivary cortisol in corticotropin-releasing hormone-test, difficult sellar
      anatomy or negative magnetic resonance imaging (MRI). Multiple direct intra
      operative micro-cytology, micro-doppler and adequate visualization techniques are
      described. Results In series 1, IPSS was performed in 13 (24%) of whom 46% had
      false adenoma lateralization. All adenomas could be removed with extensive
      pituitary exploration. Three patients had early successful re-surgery. In series
      2, with more refined MRI and endocrinology, CSS was used in only seven patients
      (15%) and all micro-adenomas were correctly localized. In three of four patients
      with persistent cortisol excess, repeat-TNS was necessary and successful. Side
      effects of TNS were minimal. Recurrence rates were 16% and 11% in series 1 and 2,
      respectively. Only four of 100 children with invasive adenomas were irradiated,
      significantly less than in other experienced pediatric centers. Conclusions Thus,
      98% remission rate could be achieved with fewer invasive pre-surgical
      investigations, such as central catheter studies, refined TNS and early repeat
      TNS. Repeat-TNS in recurrences minimized the need for irradiation.

PMID- 30098287
TI  - Somatic development at birth as influenced by maternal characteristics - an
      analysis of the German Perinatal Survey.
AB  - We investigated the effects of maternal age, body weight, body height, weight
      gain during pregnancy, smoking during pregnancy, previous live births and being a
      single mother on somatic development at birth. We analysed data from the German
      Perinatal Survey for the years 1998-2000 from eight German federal states. We had
      available data on 508,926 singleton pregnancies and neonates in total; for
      508,893 of which we could classify the neonates as small, appropriate or large
      for gestational age (SGA, AGA or LGA) based on the 10th and 90th birth weight
      percentiles. Multivariable regression analyses found statistically significant
      effects of a clinically relevant magnitude for smoking during pregnancy [odds
      ratio (OR) 2.9 for SGA births for women smoking >10 cigarettes per day], maternal
      height (OR 1.4 for SGA births for women <162 cm; OR 1.4 for LGA births for women
      >172 cm), maternal weight (OR 1.5 for SGA births for women <59 kg; OR 1.9 for LGA
      births for women >69 kg), weight gain during pregnancy (OR 1.9 for SGA births for
      women with a weight gain <8 kg; OR 2.0 for LGA births for women with a weight
      gain >18 kg) and previous live births (OR 2.1 for LGA births for women with one
      or more previous live births). Maternal age and being a single mother also had
      significant effects but their magnitude was small. Our analysis confirms the
      clinically relevant effects of smoking, maternal anthropometric measures and
      weight gain during pregnancy on neonatal somatic development.

PMID- 30098288
TI  - Prediction of postnatal developmental disabilities using the antenatal fetal
      neurodevelopmental test: KANET assessment.
AB  - Objective To assess the usefulness of the antenatal fetal neurodevelopmental test
      for the prediction of postnatal developmental disabilities. Methods Fetal
      behavior was assessed with Kurjak's antenatal neurodevelopmental test (KANET)
      using four-dimensional ultrasound between 28 and 38 weeks of gestation. A score
      range of 0-5 was characterized as abnormal, from 6 to 9 was considered
      borderline, and 10-16 was normal. After birth, follow-up was conducted for at
      least 2 years in all fetuses. Results There were 337 normal (95.47%) and 16
      borderline (4.53%) cases among the 353 cases studied, whereas there was no
      abnormal case. Five cases with postnatal developmental disabilities (one case of
      Werdig-Hoffmann disease diagnosed just after delivery, one case of autism
      spectrum disorder diagnosed at 24 months, one case of Ullrich congenital muscular
      dystrophy diagnosed at 9 months and two cases of developmental disorders
      diagnosed at age 3 and 18 months) were noted among the 337 normal cases (1.48%),
      whereas three cases with developmental disabilities (one case of motor
      development delay diagnosed at 6 months, one case of Duchenne muscular dystrophy
      diagnosed at 18 months and one case of autism spectrum disorder diagnosed at age
      30 months) were found among the 16 borderline cases (18.75%). There was a
      significant difference in the prevalence of postnatal developmental disabilities
      between the normal and borderline KANET groups (P<0.001). Conclusion Our results
      suggest that the KANET assessment may be a useful diagnostic modality for the
      prediction of postnatal developmental disabilities.

PMID- 30098289
TI  - Emerging public health threat of e-waste management: global and Indian
      perspective.
AB  - Background Electrical and electronic waste or e-waste is emerging as a major
      public health threat worldwide because of rapid advances in technology leading to
      the generation of large amount of wastes and a lack of knowledge in handling of
      these wastes. Objective The current review discusses the current e-waste problem
      worldwide, as a public health concern, with a specific focus on India and
      recommendations to have effective e-waste management. Methods This is a
      traditional review study. The burden of e-waste, regulations and its impact on
      health and the environment at the global and country level were identified using
      various search engines such as PubMed, Google Scholar, Scopus and ScienceDirect.
      Books, case studies, legislation documents, reports, original articles and other
      documents from international organizations and specific governmental agency
      websites were retrieved. In total, 33 original articles, reports, case studies
      and documents were used for this review. Results In 2016, 44.7 million tonnes of
      e-waste was generated with 2 million tonnes produced in India alone. Out of this,
      only 20% of the e-waste generated globally was handled properly. The situation is
      worse in India where more than 90% of the e-waste was handled by informal sector
      workers. An important problem with the process is that they do not take necessary
      precautionary measures before handling e-waste. Components which are not suitable
      for reuse are burnt openly or disposed of through open dumping. Most of the
      informal sector workers are illiterate making them unaware of the hazardous
      chemicals that can be released later into the water sources and the environment.
      Conclusion The current review shows that the e-waste poses a serious global
      public health threat leading to significant environmental and health risks. Most
      of the developing countries including India were found to be lagging behind in
      the implementation of environmentally sound formal recycling processes. Hence, a
      better life cycle assessment model which have been successfully implemented in
      other developing countries should be introduced in India.

PMID- 30098290
TI  - Fibromyalgia patients and healthy volunteers express difficulties and variability
      in rating experimental pain: a qualitative study.
AB  - Background and aims Despite the enormous body of literature spanning more than 50
      years describing results of pain experiments, very few have used qualitative
      methods to explore subjects' thoughts while scoring experimental painful stimuli,
      and none in the available literature have used qualitative interviews to do so.
      The current study examined how participants in experimental pain research
      delineate pain ratings to better understand the unique influences of the
      experimental setting on pain scores. An additional aim was to highlight how
      individuals with fibromyalgia and healthy volunteers are differently influenced
      by characteristics of the experimental setting. Methods This was an inductive,
      qualitative study in which individual, semi-structured interviews were performed
      with 31 fibromyalgia patients and 44 healthy volunteers. Participants had taken
      part in a pain experiment during which a thermode was used to induce painful heat
      stimuli on two skin areas. There were two primary interview questions analyzed
      for this report: (1) "Thinking back to when you were getting the heat pain on
      your leg, what were you thinking about when deciding on your pain score?" and (2)
      Participants who said that it was difficult to decide on a pain score were asked
      to, "Describe what made it difficult to choose a number." Thematic analysis was
      used to generate conceptual categories from textual data and find common themes.
      Results Three notable differences were found between fibromyalgia patients and
      healthy volunteers: (1) using current daily pain as a benchmark was seen more in
      patients, (2) wanting to appear strong in front of the study investigators was
      more common in healthy volunteers, and (3) becoming mentally fatigued from rating
      many stimuli was more common for fibromyalgia patients. Thoughts while scoring
      pain included: (1) comparing with previous or current pain, (2) self-monitoring
      of one's ability to endure the pain, (3) focusing on the physical aspects of the
      pain, (4) knowing the experimental setting is safe, (5) focusing on the pain
      scale as an anchor, and (6) desire to appear strong. Additionally, five
      difficulties in scoring experimental pain were identified: (1) falling asleep,
      (2) mentally fatigued, (3) feeling as though they were guessing, (4) having to
      make a quick decision, and (5) difficulty in being consistent. Conclusions This
      study provides insights into the thoughts of participants in experimental pain
      research studies. Participants were distracted and influenced by the experimental
      setting and some factors differed for fibromyalgia patients versus healthy
      volunteers. Implications Understanding the ways in which the experimental setting
      influences pain ratings may help pain researchers better design and interpret
      studies. Researchers can use these findings to mitigate difficulties for
      participants in experimental research to add to its validity.

PMID- 30098291
TI  - Prevalence, localization, perception and management of pain in dance: an
      overview.
AB  - Background and aims Pain is a highly complex bio-psychosocial phenomenon that may
      present a (potential) health risk and either occurs as a warning sign or a
      symptom of injury. It cannot be ruled out that these rising or changing
      requirements in dance of all styles, are reflected in health-related outcomes
      such as pain. The aim of this narrative review article is to outline an overview
      of prevalence and localization, concepts of performance pain and injury pain,
      pain perception and pain management in dance. At that consequences of pain and
      influencing factors focusing on different dance styles or forms of
      professionalism are discussed. Methods The databases CINAHL, Cochrane, Google
      Scholar, Medline, MeSH and Web of Science were screened for relevant articles.
      Results Pain prevalence in dance is very high. Pain localizations can be related
      to high dance-specific mechanical stress on the musculoskeletal system. Depending
      on the pain characteristics, dancers perceive pain as "positive" (performance
      pain) or "negative" (injury pain). Concerning pain attitudes and management,
      dancers show an increasing pain tolerance. Pain seems to be accepted as a
      necessity, often ignored and dancing is continued despite pain. Conclusions The
      findings of this article suggest that occurrence of pain, pain perception, coping
      with pain and pain history appear to be connected to dance-specific mechanical
      stress as well as to socialization in dance culture. In dance, effects of pain on
      health seem to be associated with characteristics of pain and pain behavior.
      Implications The results highlight the high relevance of pain in dance and the
      need to take into account preventive as well as rehabilitative measures.

PMID- 30098292
TI  - Toll-Like Receptor 4 (TLR4)/Cyclooxygenase-2 (COX-2) Regulates Prostate Cancer
      Cell Proliferation, Migration, and Invasion by NF-kappaB Activation.
AB  - BACKGROUND Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in
      invasion, metastasis, and survival of various cancers. Activation of TLR4 can
      promote cyclooxygenase-2 (COX-2) and nuclear factor-kappaB (NF-kappaB). However,
      little is known about the effects of TLR4/COX-2 in prostate cancer (PCa).
      MATERIAL AND METHODS In our study, TLR4 and COX-2 expressions were detected by
      quantitative real-time reverse transcription PCR (qRT-PCR) in PCa tissues (n=34).
      Cell proliferation was measured by Cell Counting Kit-8 (CCK-8) and
      carboxyfluorescein succinimidyl ester (CFSE) assays. The migration and invasion
      abilities were detected by wound healing and Transwell assays. qRT-PCR and
      western blot assays were performed to detect TLR4, COX-2, matrix
      metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinases
      (TIMP)-1, epithelial-cadherin (E-cadherin), vimentin, NF-kappaB (p65), and p-p65
      expressions. RESULTS The results revealed that TLR4 and COX-2 were upregulated in
      PCa tissues; Silencing of TLR4 or COX-2 inhibited PCa cell proliferation,
      migration, and invasion, and TLR4 siRNAs combined with COX-2 siRNAs
      synergistically suppressed PCa cell proliferation, migration, and invasion.
      Silencing of TLR4 or COX-2 also downregulated MMP-2, MMP-9, and E-cadherin
      expressions, and upregulated TIMP-1 and vimentin expressions. In addition,
      silencing of TLR4 or COX-2 inhibited p65 phosphorylation and had a synergistic
      effect. CONCLUSIONS We demonstrated that TLR4/COX-2 inhibits PCa cell
      proliferation, migration, and invasion by regulating NF-kappaB.

PMID- 30098294
TI  - Innovations in reconstructive microsurgery: Reconstructive transplantation.
AB  - In the past 20 years, reconstructive transplantation (RT) has emerged as a viable
      reconstructive option for carefully selected patients. More than 100 upper
      extremity and 40 face transplants have been performed worldwide to date.
      Concomitantly, the portfolio of reconstructive transplantation has been extended
      by additional procedures such as lower extremities, abdominal wall, neck, uterus,
      genitourinary, and pediatric transplants. In the present review article, we aim
      to summarize the current state of knowledge about this exciting field.

PMID- 30098295
TI  - Prognostic utility of atypical mitoses in patients with breast cancer: A
      comparative study with Ki67 and phosphohistone H3.
AB  - BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the presence of
      atypical mitoses is associated with poor prognosis in some types of cancer, but
      its clinical significance remains uncertain. Here, we investigated the occurrence
      of atypical mitoses in breast cancers. METHODS: Mitotic figures, including normal
      and atypical mitoses, were assessed in resected histological sections from 109
      patients with invasive carcinoma of no special type (ICNST). Comparisons with
      clinicopathological features and biomarkers such as Ki67 and phosphohistone H3
      (PHH3) were performed. RESULTS: The total number of mitotic figures, including
      atypical mitoses, was higher in situ and invasive ductal carcinoma components
      than in normal ducts. Morphological characteristics of atypical mitoses included
      multipolar, lagged, ring, asymmetrical mitoses, and anaphase bridge. Patients
      with higher total mitoses and PHH3, and the presence of atypical mitoses showed
      reduced overall survival (OS), compared to those with lower total mitoses and
      PHH3, and without atypical mitoses (P = 0.03, 0.02, and <0.001, respectively). In
      multivariate analysis, the presence of atypical mitoses alone attained
      significant correlation with shorter OS (P < 0.001). CONCLUSIONS: Atypical
      mitoses in routinely resected specimens have a robust prognostic value for ICNST
      of the breast, but its clinical utility remains to be validated in a multicenter
      large material.

PMID- 30098296
TI  - Fluorescence-guided surgery for liver tumors.
AB  - In hepatobiliary surgery, fluorescence imaging enables identification of
      subcapsular liver tumors through accumulation of indocyanine green after
      preoperative intravenous injection in cancerous tissues of hepatocellular
      carcinoma and in noncancerous hepatic parenchyma around intrahepatic
      cholangiocarcinoma and liver metastases. Indocyanine green-fluorescence imaging
      can also be used for visualizing extrahepatic bile duct anatomy and hepatic
      segmental boundaries, enhancing the accuracy of open and laparoscopic
      hepatectomy.

PMID- 30098293
TI  - Intraoperative fluorescence imaging in thoracic surgery.
AB  - Intraoperative fluorescence imaging (IFI) can improve real-time identification of
      cancer cells during an operation. Phase I clinical trials in thoracic surgery
      have demonstrated that IFI with second window indocyanine green (TumorGlow(r) )
      can identify subcentimeter pulmonary nodules, anterior mediastinal masses, and
      mesothelioma, while the use of a folate receptor-targeted near-infrared agent,
      OTL38, can improve the specificity for diagnosing tumors with folate receptor
      expression. Here, we review the existing preclinical and clinical data on IFI in
      thoracic surgery.

PMID- 30098298
TI  - Lymphovenous bypass for the treatment of lymphedema.
AB  - Lymphovenous bypass (LVB) is a form of physiological lymphedema surgery, which
      was described decades ago, but recently it is gaining popularity with improved
      microsurgical technology available. Benefits of the procedure are its
      effectiveness in treating early stage lymphedema of either the upper or lower
      extremity and having low complication profile. In the following article, the
      history of the procedure, mechanism, and details of various LVB techniques, and
      outcomes will be discussed.

PMID- 30098299
TI  - Role of Schwann cells in cutaneous wound healing.
AB  - Dermal wound healing is the process of repairing and remodeling skin following
      injury. Delayed or aberrant cutaneous healing poses a challenge for the health
      care system. The lack of detailed understanding of cellular and molecular
      mechanisms involved in this process hampers the development of effective targeted
      treatments. In a recent study, Parfejevs et al.-using state-of-the-art
      technologies, including in vivo sophisticated Cre/loxP techniques in combination
      with a mouse model of excisional cutaneous wounding-reveal that Schwann cells
      induce adult dermal wound healing. Strikingly, genetic ablation of Schwann cells
      delays wound contraction and closure, decreases myofibroblast formation, and
      impairs skin re-epithelization after injury. From a drug development perspective,
      Schwann cells are a new cellular candidate to be activated to accelerate skin
      healing. Here, we summarize and evaluate recent advances in the understanding of
      Schwann cells roles in the skin microenvironment.

PMID- 30098297
TI  - Correlation between high FBXW7 expression in pretreatment biopsy specimens and
      good response to chemoradiation therapy in patients with locally advanced
      esophageal cancer: A retrospective study.
AB  - BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) exhibits
      good reactivity to chemoradiation therapy (CRT). The dysregulation of F-Box and
      WD Repeat Domain Containing 7 (FBXW7) is associated with therapeutic resistance
      in cancer cells. However, the correlation between FBXW7 expression and CRT
      sensitivity in patients with clinical ESCC has been investigated only in few
      studies. Therefore, this study aimed to elucidate the significance of FBXW7
      expression in pretreatment biopsy specimens from patients with ESCC receiving
      CRT. METHODS: We investigated the relationship between FBXW7 expression and CRT
      sensitivity in 30 pretreatment biopsy specimens with histological grades of post
      CRT surgically resected tumors. Furthermore, we evaluated the effects of high
      FBXW7 expression on the sensitivity to cytotoxic agents, including docetaxel and
      nedaplatin, and radiation in ESCC cells in vitro. RESULTS: High FBXW7 expression
      before CRT correlated with a good pathological CRT response in patients with
      advanced ESCC (P < .05). Further, our in vitro data showed that both chemo and
      radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7
      compared with mock cells because of the degradation of the anti-apoptotic protein
      MCL1. CONCLUSIONS: The evaluation of FBXW7 expression before CRT treatment is a
      potential predictor of good responders among patients with ESCC receiving CRT.

PMID- 30098300
TI  - Melatonin improves hyperglycemia induced damages in rat brain.
AB  - BACKGROUND: Diabetes mellitus is an endocrine disorder which is characterized by
      the development of resistance to the cellular activity of insulin or inadequate
      insulin production. It leads to hyperglycemia, prolonged inflammation, and
      oxidative stress. Oxidative stress is assumed to play an important role in the
      development of diabetic complications. Melatonin is the hormone that interacts
      with insulin in diabetes. Therefore, in this study, the effects of melatonin
      treatment with or without insulin were examined in diabetic rat brain. METHODS:
      Rats were divided into five groups as control, diabetes, diabetes + insulin,
      diabetes + melatonin, and diabetes + melatonin + insulin. Experimental diabetes
      was induced by streptozotocin (60 mg/kg, i.p.). Twelve weeks after diabetes
      induction, rats were decapitated. Malondialdehyde, glutathione, sialic acid and
      nitric oxide levels, superoxide dismutase, catalase, glutathione-S-transferase,
      myeloperoxidase, and tissue factor activities were determined in brain tissue.
      RESULTS: Melatonin alone showed its antioxidant effect by increasing brain
      glutathione level, superoxide dismutase, catalase, and glutathione-S-transferase
      activities and decreasing malondialdehyde level in experimental diabetes.
      Although insulin did not have a significant effect on glutathione and glutathione
      S-transferase, its effects on lipid peroxidation, superoxide dismutase, and
      catalase were similar to melatonin; insulin also decreased myolopeoxidase
      activity and increased tissue factor activity. Combined melatonin and insulin
      treatment mimicked the effects of insulin. CONCLUSION: Addition of melatonin to
      the insulin treatment did not change the effects of insulin, but the detailed
      role of melatonin alone in the treatment of diabetes merits further experimental
      and clinical investigation.

PMID- 30098301
TI  - Sex disparity in cardiovascular mortality rates associated with diabetes.

PMID- 30098302
TI  - National practice patterns of completion lymph node dissection for sentinel node
      positive melanoma.
AB  - BACKGROUND AND OBJECTIVES: Close observation may be an appropriate alternative to
      completion lymph node dissection (CLND) for selected patient populations,
      especially those with minimal tumor burden in the sentinel lymph node (SLN). In
      this study, we examined the practice patterns of CLND utilization. METHODS: Using
      the National Cancer Database, we examined CLND utilization in SLN-positive
      patients diagnosed with clinically node-negative Stage III melanoma from 2012 to
      2015. Hierarchical logistic regression models were constructed to assess the
      factors associated with observation after positive SLN biopsy (SLNB). RESULTS: Of
      the 131 171 patients identified, 55 688 (42.5%) underwent SLNB and 7200 (12.9%)
      had an SLN with a metastatic disease. CLND was performed in 57.0% of the patients
      with a positive SLNB. Patients were more likely to forgo CLND if the primary
      tumor was located on the lower extremity (odds ratio [OR], 1.65, 95% confidence
      interval [CI], 1.40-1.94), were older (P < 0.001), had multiple comorbidities
      (OR, 1.61, 95% CI, 1.19-2.20), or were diagnosed with melanoma in 2015 (OR, 1.33,
      95% CI, 1.13-1.56 vs 2012). CONCLUSIONS: CLND utilization varied based on patient
      factors and decreased over time. As evidence supports close observation in
      selected patient populations with low SLN tumor burden, monitoring is needed to
      ensure that CLND is performed in the appropriate patient populations. However,
      this will require improvements in the data collected by cancer registries.

PMID- 30098303
TI  - Short- and long-term outcomes of middle hepatic vein-oriented hepatectomy for
      advanced perihilar cholangiocarcinoma.
AB  - BACKGROUND: This study aimed to compare clinical outcomes of the middle hepatic
      vein (MHV)-oriented versus conventional hemihepatectomy for perihilar
      cholangiocarcinoma (PHC). METHODS: From 2008 to 2017, medical records of patients
      undergoing hemihepatectomy with caudate lobectomy for advanced PHC were reviewed
      retrospectively. MHV-oriented hepatectomy was defined as full exposure of the MHV
      on the dissection plane. Predictors of morbidity and survival were identified.
      RESULTS: A total of 125 patients were enrolled. MHV-oriented and conventional
      hepatectomies were performed in 44 and 81 patients, respectively. The curative
      resection rate, blood loss, transfusion, and survival were comparable between two
      groups; however, severe morbidity rate was significantly lower in the MHV
      oriented group (9.1% vs 38.3%, P < 0.001). MHV-oriented approach was an
      independent predictor of severe morbidity, as were the age, bilirubin level, and
      blood transfusion. Severe morbidity was associated with significantly decreased
      overall survival and recurrence-free survival (RFS) (median 29.0 vs 46.9 months,
      P = 0.011 and 20.3 vs 31.1 months, P = 0.003, respectively). Multivariate
      analysis revealed that severe morbidity independently predicted shorter RFS (P =
      0.025). CONCLUSIONS: MHV-oriented approach for advanced PHC is safe and
      associated with a significant decrease in severe morbidity. Severe morbidity
      adversely affects survival after surgery; therefore, optimal preoperative
      preparation and MHV-oriented hepatectomy with meticulous dissection remain of
      critical importance.

PMID- 30098305
TI  - Metabotypes Related to Meat and Vegetable Intake Reflect Microbial, Lipid and
      Amino Acid Metabolism in Healthy People.
AB  - SCOPE: The objective of this study is to develop a new methodology to identify
      the relationship between dietary patterns and metabolites indicative of food
      intake and metabolism. METHODS AND RESULTS: Plasma and urine samples from healthy
      Swiss subjects (n = 89) collected over two time points are analyzed for a panel
      of host-microbial metabolites using GC- and LC-MS. Dietary intake is evaluated
      using a validated food frequency questionnaire. Dietary pattern clusters and
      relationships with metabolites are determined using Non-Negative Matrix
      Factorization (NNMF) and Sparse Generalized Canonical Correlation Analysis
      (SGCCA). Use of NNMF allows detection of latent diet clusters in this population,
      which describes a high intake of meat or vegetables. SGCCA associates these
      clusters to i) diet-host microbial and lipid associated bile acid metabolism, and
      ii) essential amino acid metabolism. CONCLUSION: This novel application of NNMF
      and SGCCA allows detection of distinct metabotypes for meat and vegetable dietary
      patterns in a heterogeneous population. As many of the metabolites associated
      with meat or vegetable intake are the result of host-microbiota interactions, the
      findings support a role for microbiota mediating the metabolic imprinting of
      different dietary choices.

PMID- 30098304
TI  - Gene expression profiles of rat MMECs with different glucose levels and fgl2 gene
      silencing.
AB  - BACKGROUND: Cardiac microvascular endothelial cells (MMECs) is one of the key
      factors in the process of diabetic cardiomyopathy, a common chronic complication
      of diabetes. Fibrinogen-like protein 2 (FGL2) is linked to apoptosis,
      angiogenesis, and inflammatory response, all of which also occur in diabetes.
      Thus, we investigate the role of FGL 2 and other genes in the pathology of
      diabetic cardiomyopathy. METHODS: In the present study, we used high-throughput
      microarray to profile gene expression in rat myocardial MMECs with or without
      silencing the fgl2 gene and in different glucose environments. We use volcanic
      maps to isolate genes with significantly different expression levels between
      conditions, using the standard statistical criteria of fold changes >=1.5 and P
      values <=0.05. From this list, we identified genes with the most signicant
      changes in RNA levels and confirmed their protein-level changes with Western
      blot. Furthermore, bioinformatic analysis predicts possible pathophysiology and
      clinical relevance of these proteins in diabetic cardiomyopathy. RESULTS: We
      identified 17 upregulated and 15 downregulated genes caused by silencing fgl2
      gene. Most of them are involved in metabolism, ion transport, cell membrane
      surface recognition signal modification, inflammatory response, and immune
      response. Using Western blot, we were able to confirm protein-level expression
      changes of three genes. Specifically, in both normal and high glucose conditions,
      silencing fgl2 significantly decreased the expression levels of CCL3 and PLAGL1
      while increasing the expression level of CTSC. Significantly, bioinformatic
      analyses show that CCL3 is related to type 1 diabetes, PLAGL1 to cardiomyocytes,
      and CTSC to albuminuria in type 2 diabetes. CONCLUSIONS: Our study provides clues
      for further studies on the mechanism of diabetic cardiomyopathy as well as
      function of FGL2 in this process, potentially offering new therapeutic strategies
      for treating diabetic cardiomyopathy.

PMID- 30098306
TI  - Introducing the subdermal free flap: Preserving the ultrathin-free skin flap
      option in morbidly obese patients.
AB  - In the morbidly obese population (BMI > 35), distal extremity defects are
      difficult to reconstruct. Traditional skin flaps are several centimeters in
      thickness in obese patients; however, a new plane superficial to the scarpal
      plane has demonstrated success in these patients. In this report, we present a 62
      year-old female (BMI = 44.81) with a chronic lower extremity wound. A
      suprascarpal thin flap (approximately 1 cm in thickness) was harvested from the
      thigh and transferred successfully with no wound-healing issues.

PMID- 30098307
TI  - The effect of contralateral prophylactic mastectomy on breast-related charges: A
      5-year analysis.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to determine charges
      following unilateral mastectomy (UM) and bilateral mastectomy (BM) for patients
      with unilateral breast cancer (UBC). We hypothesized that BM may be associated
      with fewer charges over time. METHODS: A retrospective review was conducted of
      patients with UBC treated between 2006 and 2010 with UM and BM in a large
      healthcare system. Institutional billing data were investigated for 5 years
      postoperatively to calculate the immediate and subsequent charges of all
      inpatient and outpatient breast-related care associated with the initial
      diagnosis for a subset of patients identified using propensity score matching
      method. RESULTS: A subset of matched patients (n = 320) undergoing UM (n = 160)
      or BM (n = 160) were included in this analysis. At 1 year, there was a trend
      toward lower total charges following UM as compared with BM (median, $125 230 vs
      $138 467; P = .6075). However, during years 2 to 5, total charges were
      significantly higher following UM vs BM ($22 128 vs $13 478; P = .0116).
      CONCLUSIONS: While initially higher, overall charges for BM are lower than UM
      between 2 and 5 years out from surgery. Further study is necessary to determine
      if this trend is sustained over the long term. These data can inform patient
      decision making regarding mastectomy for their breast cancer.

PMID- 30098308
TI  - L-tryptophan administration and increase in cerebral serotonin levels: Systematic
      review.
AB  - The amino acid tryptophan (2-Amino-3-(lH-indol-3-yl)-propanoic acid; Trp) is a
      precursor of the neurotransmitter serotonin (5-hydroxytryptamine; 5-HT) that
      performs various brain functions. The administration of Trp is used in
      experimental studies to manipulate the serotonergic system, however the dose of
      Trp required to raise brain 5-HT levels is controversial. The aim of this study
      was to systemically review the effect of the administration of different doses of
      Trp on cerebral 5-HT levels. Two independent authors conducted a systematic
      review in the electronic databases. Twenty-five studies were included in the
      present review. Trp was administered orally, intraperitoneally or subcutaneous in
      adult animals. The brain 5-HT levels elevated after Trp administration in
      different intensities, dependent of the brain region evaluated and the time of
      administration. Further studies are needed to assess the dose-response of Trp
      administration to brain 5-HT levels.

PMID- 30098310
TI  - Introduction to Neurogenetics.
AB  - Genetic variation can directly cause or increase susceptibility to neurologic
      diseases. An explosion of new genetic technologies has enabled the
      characterization of specific genes responsible for many neurologic diseases and
      has provided fundamentally new insight into their pathophysiology. These
      advancements, along with recent breakthroughs in gene therapy, are beginning to
      result in the translation of an individual's genetic sequence into targeted
      treatment strategies. This review aims to introduce key genetic concepts and to
      illustrate how these principles apply in cases of rare, single-gene neurologic
      diseases as well as more common, polygenic diseases that are encountered
      frequently in clinical practice.

PMID- 30098309
TI  - Potassium usnate toxicity against embryonic stages of the snail Biomphalaria
      glabrata and Schistosoma mansoni cercariae.
AB  - The snail Biomphalaria glabrata is the most important vector for Schistosoma
      mansoni. Control of this vector to prevent the spread of schistosomiasis is
      currently performed with the application of a niclosamide molluscicide, which is
      highly toxic to the environment. Screening of substances that show embryotoxic
      molluscicidal potential as well as have detrimental effects on cercariae is very
      relevant for the control of schistosomiasis, as the efficacy of prevention of the
      disease is increased if it acts as a molluscicide as well as on the cercariae of
      S. mansoni. The aim of this work was to evaluate the effect of potassium usnate
      derived from usnic acid on different stages of embryonic development of B.
      glabrata and on S. mansoni cercariae. After 24 h of exposure, potassium usnate
      showed embryotoxic activity across all embryonic stages. The values obtained from
      the LC50 for the embryonic stages were the following: blastula 5.22 MUg/mL,
      gastrula 3.21 MUg/mL, trochophore 3.58 MUg/mL, veliger 2.79, and hippo stage 2.52
      MUg/mL. Against S. mansoni cercariae, it had LC90 and 100% mortality at
      concentrations of 2.5 and 5 MUg/mL in 2 h of exposure. In conclusion, this is the
      first report of potassium usnate toxicity on the embryonic stages of B. glabrata
      and cercariae of S. mansoni, and this study shows the potassium usnate as a
      promising agent for the control of mansoni schistosomiasis.

PMID- 30098311
TI  - Advanced Therapies for Massive Pulmonary Embolism.

PMID- 30098312
TI  - Pharmacological blockade of fatty acid amide hydrolase (FAAH) by URB597 improves
      memory and changes the phenotype of hippocampal microglia despite ethanol
      exposure.
AB  - Changes in endogenous cannabinoid homeostasis are associated with both ethanol
      related neuroinflammation and memory decline. Extensive research is still
      required to unveil the role of endocannabinoid signaling activation on
      hippocampal microglial cells after ethanol exposure. Either microglial
      morphology, phenotype and recruitment may become notably altered after chronic
      alcohol-related neurodegeneration. Here, we evaluated the pharmacological effects
      of fatty-acid amide-hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg),
      oleoylethanolamide (OEA, 10 mg/kg), arachidonoylethanolamide (AEA, 10 mg/kg), the
      CB1 receptor agonist ACEA (3 mg/kg) and the CB2 receptor agonist JWH133 (0.2
      mg/kg) administered for 5 days in a rat model of subchronic (2 weeks) ethanol
      diet (11% v/v) exposure. URB597 turned to be the most effective treatment. URB597
      increased microglial (IBA-1+) cell population, and changed morphometric features
      (cell area and perimeter, roughness, fractal dimension, lacunarity) associated
      with activated microglia in the hippocampus of ethanol-exposed rats. Regarding
      innate immune activity, URB597 specifically increased mRNA levels of toll-like
      receptor 4 (TLR4), glial fibrillary acidic protein (Gfap) and the chemokine
      stromal cell-derived factor 1 (SDF-1alpha/CXCL12), and elevated the cell
      population expressing the chemokine receptors CX3CR1, CCR2 and CCR4 in the
      ethanol-exposed rat hippocampus. Contrary to ethanol effect, URB597 reduced mRNA
      levels of Iba-1, Tnfalpha, IL-6 and the monocyte chemoattractant protein-1 (MCP
      1/CCL2), as well as cell population expressing iNOS. URB597 effects on
      hippocampal immune system were accompanied by changes in short and long-term
      visual recognition memory. These results suggest that FAAH inhibition may
      modulates hippocampal microglial recruitment and activation that can be
      associated with improved hippocampal-dependent memory despite ethanol exposure.

PMID- 30098313
TI  - MicroRNA-143-3p inhibits growth and invasiveness of melanoma cells by targeting
      cyclooxygenase-2 and inversely correlates with malignant melanoma progression.
AB  - Malignant melanoma is one of the most leading form of skin cancer associated with
      a low patient survival rate. Increasing evidence revealed that microRNAs (miRNAs)
      play a crucial role in the occurrence and development of several form of cancer
      including melanoma. In this study, we aimed at investigating the expression and
      role of miR-143-3p in human malignant melanoma. Our results showed that the
      expression of miR-143-3p was lower in human melanoma cells, as well as human
      biopsy specimens, when compared to normal human melanocytes. Ectopic expression
      of miR-143-3p in human melanoma cells inhibited proliferation, migration,
      invasion and promoted apoptosis acting through a molecular mechanism that, at
      least in part, is dependent on inhibition of cyclooxygenase-2 (COX-2) gene.
      Collectively, these results demonstrate that miR-143-3p could represent at the
      same time, a new early diagnostic marker and therapeutic target acting as tumor
      suppressor in melanoma cancer.

PMID- 30098314
TI  - Study on activation and improvement of crop seeds by the application of plasma
      treating seeds equipment.
AB  - Plasma technology is applied in various fields, which involves in stimulating the
      germinability and amelioration of crop seeds, increasing crop production and
      displaying high quality, stress tolerance and other beneficial traits. Crucial
      techniques of plasma treating seeds (PTS) are introduced and the technical
      applications of activating seeds with key parameters of plasma discharge
      equipment are discussed. With a lot of laboratory researches and field tests, the
      biological effects of non-thermal PTS are analyzed. Meanwhile, a preliminary
      discussion about the PTS mechanism and technical popularization is made. Main
      findings including non-thermal plasma treatment are as follows: (i) the
      germination rates of the maize seeds were 72% or so if treated by 140 W-160 W
      power, which was the highest; (ii) the length of the wheat radicle and germ was
      increased effectively by 8.7 cm and 3.3 cm, and the dry weight of the wheat was
      increased by 10.1%; (iii) the germinative energy and germinating percentage of
      the aging seeds could be greatly increased. It is concluded that PTS enhances
      seed germination as well as plant growth, meanwhile, more crops are yielded and
      the quality is improved. Both technologies and plasma discharge equipment have
      significant applicative value and popularize in agriculture.

PMID- 30098315
TI  - Reply.

PMID- 30098316
TI  - Effects of GnRH and the dual regulatory actions of GnIH in the pituitary explants
      and brain slices of Astyanax altiparanae males.
AB  - The pituitary gonadotropins, Fsh (follicle-stimulating hormone) and Lh
      (luteinizing hormone), regulate testicular development and functions in all
      vertebrates. At the pituitary, different signaling systems regulate the synthesis
      and secretion of the gonadotropins, such as the hypothalamic neuropeptides GnRH
      (gonadotropin-releasing hormone) and GnIH (gonadotropin-inhibitory hormone).
      While GnRH exerts stimulatory roles, the actions of GnIH remain controversial for
      many teleost species. Therefore, the aim of this study was to evaluate the in
      vitro effects of chicken GnRH2 (cGnRH2) and zebrafish GnIH-3 (zGnIH-3) on the
      male gonadotropin and GnRH system expression using pituitary explants and brain
      slices from a neotropical species with economical and ecological relevance,
      Astyanax altiparanae. Our results showed that in males, cGnRH2 increased fshb and
      lhb mRNA levels in the pituitary explants. Interestingly, zGnIH-3 has no effect
      on basal gonadotropin expression, however zGnIH-3 decreased the cGnRH2-induced
      fshb and lhb transcripts in male pituitary explants. In the male brain slices,
      zGnIH-3 showed stimulatory effects, increasing gnrh2 mRNA levels. Overall, our
      results suggested that GnIH seems to have dual regulatory actions on gonadotropin
      and GnRH2 expression of A. altiparanae males. This study provided basic
      information on endocrine regulation of A. altiparanae reproduction, and the
      obtained results will expand our knowledge, improving the reproductive management
      of this economically important freshwater species.

PMID- 30098318
TI  - Resolution of inflammation and mood disorders.
AB  - Relationship between mood disorders and inflammation is now well-documented,
      although molecular mechanisms are not understood. Previously mostly pro
      inflammatory cytokines of immune system (IL-6, TNF, etc.) were taken into
      account. However, recent understanding of resolution of inflammation as an active
      process drew attention to mediators of resolution, which include both proteins
      and omega-3 and omega-6 polyunsaturated fatty acids derivatives (resolvins,
      cyclopentenone prostaglandins, etc.). This review takes into account new data on
      resolution of inflammation and action of mediators of resolution in models of
      depression. New facts and ideas about mechanisms of chronic inflammation onset
      are considered in relation to mood disorders. Basic control mechanisms of
      inflammation at the cellular level and the role of resolution substances in
      regulation of depression and other mood disorders are discussed. Signaling
      systems of innate immunity located in non-immune cells and their ability to
      generate substances that affect an onset of depression are reviewed. A novel
      hypothesis of depression as a type of abnormal resolution is proposed.

PMID- 30098317
TI  - Measuring immune responses to pneumococcal vaccines.
AB  - Quantitative assays that measure immune response to pneumococcal vaccines are not
      only important for the evaluation of vaccine immunogenicity and efficacy, but are
      also utilized in the clinical diagnosis of immune deficiency syndromes.
      Analytical methods have progressed in order to meet changing demands in both of
      these areas, from early methods to ELISA, and most recently multiplex bead array
      assays and opsonophagocytosis assays (OPA). It is necessary to understand the
      evolution of such techniques and the criteria for their interpretation in order
      to better inform the application of currently available methods, and to guide
      future investigation into assay development.

PMID- 30098319
TI  - A two-phase model of early fibrous cap formation in atherosclerosis.
AB  - Atherosclerotic plaque growth is characterised by chronic, non-resolving
      inflammation that promotes the accumulation of cellular debris and extracellular
      fat in the inner artery wall. This material is highly thrombogenic, and plaque
      rupture can lead to the formation of blood clots that occlude major arteries and
      cause myocardial infarction or stroke. In advanced plaques, vascular smooth
      muscle cells (SMCs) are recruited from deeper in the artery wall to synthesise a
      cap of fibrous tissue that stabilises the plaque and sequesters the thrombogenic
      plaque content from the bloodstream. The fibrous cap provides crucial protection
      against the clinical consequences of atherosclerosis, but the mechanisms of cap
      formation are poorly understood. In particular, it is unclear why certain plaques
      become stable and robust while others become fragile and dangerously vulnerable
      to rupture. We develop a multiphase model with non-standard boundary conditions
      to investigate early fibrous cap formation in the atherosclerotic plaque. The
      model is parameterised using data from a range of in vitro and in vivo studies,
      and includes highly nonlinear mechanisms of SMC proliferation and migration in
      response to an endothelium-derived chemical signal. We demonstrate that the model
      SMC population naturally evolves towards a steady-state, and predict a rate of
      cap formation and a final plaque SMC content consistent with experimental
      observations in mice. Parameter sensitivity simulations show that SMC
      proliferation makes a limited contribution to cap formation, and demonstrate that
      stable cap formation relies primarily on a critical balance between the rates of
      SMC recruitment to the plaque, chemotactic SMC migration within the plaque and
      SMC loss by apoptosis or phenotype change. This model represents the first
      detailed in silico study of fibrous cap formation in atherosclerosis, and
      establishes a multiphase modelling framework that can be readily extended to
      investigate many other aspects of plaque development.

PMID- 30098320
TI  - A mathematical model of type 1 diabetes involving leptin effects on glucose
      metabolism.
AB  - Leptin, a hormone released from fat cells in adipose tissues, was recently found
      to be capable of normalizing glucose metabolism in animals. Clinical data on
      patients with lipodystrophy indicates that leptin may have a positive effect on
      glucose metabolism in individuals with diabetes. There are growing expectations
      that leptin can improve the current insulin treatment for patients with type 1
      diabetes. We investigated this possibility through in silico experiments based on
      a mathematical model of diabetes, which is currently the only mode of research
      that eliminates human risk. A model of the brain-centered glucoregulatory system,
      in which leptin plays a central role, was constructed and integrated within a
      conventional model of insulin/glucose dynamics. The model has been validated
      using experimental data from animal studies. The in silico combination
      experiments showed excellent therapeutic performance over insulin monotherapy.

PMID- 30098321
TI  - The salient role of microRNAs in atherogenesis.
AB  - Atherosclerosis, a chronic inflammatory condition that is characterized by the
      accumulation of lipid-loaded macrophages, occurs preferentially at the arterial
      branching points where disturbed flow is prominent. The pathogenesis of
      atherosclerotic lesion formation is a multistage process involving multiple cell
      types, inflammatory mediators and hemodynamic forces in the vessel wall in
      response to atherogenic stimuli. Researches from the past decade have uncovered
      the critical roles of microRNAs (miRNAs) in regulating multiple
      pathophysiological effects and signaling pathways in endothelial cells (ECs),
      vascular smooth muscle cells (VSMCs), macrophages and lipid homeostasis, which
      are key in atherosclerotic lesion formation. The expression of these miRNAs are
      either in response to biomechanical (flow-responsive) or biochemical (non-flow
      responsive) stimuli. Recent evidences also indicate an important role for long
      non-coding RNAs (lncRNAs) in mediating several atherosclerotic processes. In this
      review, we provide a detailed summary on the current paradigms in miRNA-dependent
      regulation, the emerging role of lncRNAs in the initiation and progression of
      atherosclerosis, and clinical interventions targeting these in an attempt to
      develop novel diagnostics and treatments for atherosclerosis.

PMID- 30098322
TI  - The advantages of next-generation sequencing technology in the detection of
      different sources of abscess.

PMID- 30098323
TI  - Omics, big data and machine learning as tools to propel understanding of
      biological mechanisms and to discover novel diagnostics and therapeutics.

PMID- 30098325
TI  - Evaluating the Efficacy and Safety of Silodosin on Nocturia in Patients With
      Benign Prostatic Hyperplasia: A Multicenter, Prospective, Open-label, Single-arm,
      Phase IV Trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of silodosin on nocturia in
      patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: This was
      a 12-week, single-arm, open-label, prospective, multicenter study. The study
      included men aged 50years or older with nocturia (>=2 events/night) based on a
      voiding diary, an International Prostate Symptom Score (IPSS) >=8, and a quality
      of life score >=3. Enrolled patients received 8mg of silodosin once daily for 12
      weeks. We evaluated changes in the mean number of nocturia episodes (using a
      voiding diary) from baseline to the final assessment. Safety assessments included
      the rate of adverse events and adverse drug reactions. RESULTS: There were 118
      patients included in the safety evaluation analysis, and 112 patients in the full
      analysis set group. The number of nocturia episodes decreased significantly after
      12 weeks of treatment with silodosin (-1.12 +/- 1.05, P < .0001). The secondary
      efficacy variables, including IPSS, overactive bladder symptom score and
      International Consultation on Incontinence Questionnaire-Nocturia score, also
      improved with treatment (P < .0001). There were abnormal drug reactions in 11.8%
      of patients. The most common adverse drug reaction was an ejaculatory disorder
      (7.6%). There were no significant adverse drug reactions reported. CONCLUSION:
      Silodosin was found to be safe and effective in the treatment of nocturia in
      patients with BPH.

PMID- 30098324
TI  - Liver-specific ablation of insulin-degrading enzyme causes hepatic insulin
      resistance and glucose intolerance, without affecting insulin clearance in mice.
AB  - : The role of insulin-degrading enzyme (IDE), a metalloprotease with high
      affinity for insulin, in insulin clearance remains poorly understood. OBJECTIVE:
      This study aimed to clarify whether IDE is a major mediator of insulin clearance,
      and to define its role in the etiology of hepatic insulin resistance. METHODS: We
      generated mice with liver-specific deletion of Ide (L-IDE-KO) and assessed
      insulin clearance and action. RESULTS: L-IDE-KO mice exhibited higher (~20%)
      fasting and non-fasting plasma glucose levels, glucose intolerance and insulin
      resistance. This phenotype was associated with ~30% lower plasma membrane insulin
      receptor levels in liver, as well as ~55% reduction in insulin-stimulated
      phosphorylation of the insulin receptor, and its downstream signaling molecules,
      AKT1 and AKT2 (reduced by ~40%). In addition, FoxO1 was aberrantly distributed in
      cellular nuclei, in parallel with up-regulation of the gluconeogenic genes Pck1
      and G6pc. Surprisingly, L-IDE-KO mice showed similar plasma insulin levels and
      hepatic insulin clearance as control mice, despite reduced phosphorylation of the
      carcinoembryonic antigen-related cell adhesion molecule 1, which upon its insulin
      stimulated phosphorylation, promotes receptor-mediated insulin uptake to be
      degraded. CONCLUSION: IDE is not a rate-limiting regulator of plasma insulin
      levels in vivo.

PMID- 30098326
TI  - Characterization of the neuroinvasive profile of a pseudorabies virus recombinant
      expressing the mTurquoise2 reporter in single and multiple injection experiments.
AB  - BACKGROUND: Viral transneuronal tracing has become a well established technology
      used to define the synaptic architecture of polysynaptic neural networks. NEW
      METHOD: In this report we define the neuroinvasive profile and reporter
      expression of a new recombinant of the Bartha strain of pseudorabies virus (PRV).
      The new recombinant, PRV-290, expresses the mTurquoise2 fluorophor and is
      designed to complement other isogenic recombinants of Bartha that express
      different reporters of infection. Results & Comparison with Existing Methods: PRV
      290 was injected either alone or in combination with isogenic recombinants of PRV
      that express enhanced green fluorescent protein (EGFP; PRV-152) or monomeric red
      fluorescent protein (mRFP; PRV-614). Circuits previously defined using PRV-152
      and PRV-614 were used for the analysis. The data demonstrate that PRV-290 is a
      retrograde transneuronal tracer with temporal kinetics similar to those of its
      isogenic recombinants. Stable expression of the diffusible mTurquoise2 reporter
      filled infected neurons, with the extent and intensity of labeling increasing
      with advancing post inoculation survival. In multiple injection experiments, PRV
      290 established productive infections in neurons also replicating PRV-152 and/or
      PRV-614. This novel demonstration of three recombinants infecting individual
      neurons represents an important advance in the technology. CONCLUSION:
      Collectively, these data demonstrate that PRV-290 is a valuable addition to the
      viral tracer toolbox for transneuronal tracing of neural circuitry.

PMID- 30098328
TI  - What bilateral damage of the superior parietal lobes tells us about visual
      attention disorders in developmental dyslexia.
AB  - Neuroimaging studies have identified the superior parietal lobules bilaterally as
      the neural substrates of reduced visual attention (VA) span in developmental
      dyslexia. It remains however unclear whether the VA span deficit and the deficits
      in temporal and spatial attention shifting also reported in dyslexic children
      reflect a unitary spatio-temporal deficit of attention - probably linked to
      general posterior parietal dysfunction- or the dysfunction of distinct
      attentional systems that relate to different neural substrates. We explored this
      issue by testing an adult patient, IG, with a specific damage of the bilateral
      superior parietal lobules after stroke, on tasks assessing the VA span as well as
      temporal and spatial attention shifting. IG demonstrated a very severe VA span
      deficit, but preserved temporal attention shifting. Exogenous spatial orientation
      shifting was spared but her performance was impaired in endogenous attention. The
      overall findings show that distinct sub-systems of visual attention can be
      dissociated within the parietal lobe, suggesting that different attentional
      systems associated with specific neural networks can be selectively impaired in
      developmental dyslexia.

PMID- 30098329
TI  - Observation of an action with a congruent contextual background facilitates
      corticospinal excitability: A combined TMS and eye-tracking experiment.
AB  - Action observation produces activity in similar regions of the brain to those
      involved in action execution and can offer an effective intervention for motor
      (re)learning, although optimal viewing conditions for such interventions remain
      to be established. In this experiment, single-pulse transcranial magnetic
      stimulation (TMS) and eye-tracking were used simultaneously to investigate the
      effect of manipulating background context on both corticospinal excitability and
      visual attention during action observation. Twenty-four participants observed
      four different videos: (i) a static hand holding a sponge (control condition);
      and an index finger-thumb pinch of a sponge against (ii) a plain black
      background; (iii) a background containing objects that were incongruent with the
      observed action; and (iv) a background containing objects that were congruent
      with the observed action. TMS was delivered to the hand representation of the
      left primary motor cortex, and motor evoked potentials were recorded from the
      first dorsal interosseous and abductor digiti minimi muscles of the right hand.
      Eye movements were recorded throughout the experiment. Results indicated that
      corticospinal excitability was facilitated during the congruent context condition
      compared to both the static hand and plain black background conditions. In
      addition, the number of fixations and percentage of time participants spent
      fixating on the background scene were significantly greater during the
      incongruent and congruent conditions compared to the static hand and plain black
      background conditions. These results indicate that the provision of additional
      visual information that is congruent with the observed movement contributes to a
      facilitation of corticospinal excitability by providing the observer with
      information regarding the goal and intention of the observed action. Providing
      congruent contextual information may enhance the efficacy of action observation
      interventions for motor (re)learning.

PMID- 30098330
TI  - Sirtuin 5 overexpression attenuates glucolipotoxicity-induced pancreatic beta
      cells apoptosis and dysfunction.
AB  - Recently, SIRT5 was reported to be a predominant desuccinylase and demalonylase
      in mitochondria. Ablation of SIRT5 enhances the systemic succinylation and
      malonylation of mitochondrial proteins, including various metabolic enzymes;
      however, its function in pancreatic beta cells has not yet been clarified. In
      this study, we evaluated the effects of SIRT5 overexpression on glucolipotoxicity
      induced apoptosis in beta cell lines. Full-length SIRT5, which preferentially
      targeted to mitochondria and partially to the nucleus and cytoplasm, was
      overexpressed in NIT-1 cells. Chronic exposure to excess palmitate and glucose
      (High-PA-G) induced apoptosis and suppressed glucose-stimulated insulin secretion
      in beta cells. SIRT5 overexpression significantly alleviated apoptosis under the
      High-PA-G condition, accompanied by suppressed Caspase 3 activity and reduced
      malondialdehyde levels. SIRT5 overexpression also improved beta cell secretory
      capacity in response to glucose under the High-PA-G condition, suggesting its
      protective role in beta cell function. Furthermore, SIRT5 overexpression reversed
      the decreasing trend of anti-apoptotic factors BCL-2 and BCL-XL expression under
      High-PA-G condition. Further regulation mechanisms between SIRT5 and these anti
      apoptotic factors remains to be explored in future studies. Our data reveal that
      SIRT5 is a potentially protective factor for pancreatic beta cells against
      glucolipotoxicity-induced apoptosis and cell dysfunction.

PMID- 30098331
TI  - Protein kinase C mediated internalization of ErbB2 is independent of clathrin,
      ubiquitination and Hsp90 dissociation.
AB  - Overexpression of ErbB2 is frequent in cancer and understanding the mechanisms
      which regulate its expression is important. ErbB2 is considered endocytosis
      resistant. It has no identified ligand, but upon heterodimerization it is a
      potent mediator of proliferative signaling. A recent study established a role for
      protein kinase C (PKC) in internalization and recycling of ErbB2. We have now
      further investigated the molecular mechanisms involved in PKC-mediated
      downregulation of ErbB2. We confirm that PMA-induced PKC activation causes ErbB2
      internalization, but while the Hsp90 inhibitor 17-AAG induced ErbB2 degradation,
      PMA had no such effect. When combined with 17-AAG, PMA had additive effect on
      ErbB2 internalization indicating that Hsp90 inhibition and PKC activation induce
      internalization by alternative mechanisms. We confirm that while 17-AAG-induced
      internalization was clathrin-mediated, PMA-induced internalization was clathrin
      independent. This difference may be explained by while both 17-AAG and PMA
      reduced the constitutive tyrosine phosphorylation of ErbB2, only 17-AAG induced
      Hsp90 dissociation, Hsp70 recruitment and ubiquitination of ErbB2. Importantly,
      since PMA induced internalization of ErbB2, but not dissociation of Hsp90, Hsp90
      does not per se retain ErbB2 at the plasma membrane. The morphology of the
      compartment into which receptors are sorted upon PKC activation has not
      previously been identified. By immuno-electron microscopy, we show that PMA sorts
      ErbB2 into a complex tubulovesicular or cisternal organelle resembling a
      previously described endocytic recycling compartment.

PMID- 30098332
TI  - Epidermal growth factor receptor: Structure-function informing the design of
      anticancer therapeutics.
AB  - Research on the epidermal growth factor (EGF) family and the family of receptors
      (EGFR) has progressed rapidly in recent times. New crystal structures of the
      ectodomains with different ligands, the activation of the kinase domain through
      oligomerisation and the use of fluorescence techniques have revealed profound
      conformational changes on ligand binding. The control of cell signaling from the
      EGFR-family is complex, with heterodimerisation, ligand affinity and signaling
      cross-talk influencing cellular outcomes. Analysis of tissue homeostasis
      indicates that the control of pro-ligand processing is likely to be as important
      as receptor activation events. Several members of the EGFR-family are
      overexpressed and/or mutated in cancer cells. The perturbation of EGFR-family
      signaling drives the malignant phenotype of many cancers and both inhibitors and
      antagonists of signaling from these receptors have already produced therapeutic
      benefits for patients. The design of affibodies, antibodies, small molecule
      inhibitors and even immunotherapeutic drugs targeting the EGFR-family has yielded
      promising new approaches to improving outcomes for cancer patients. In this
      review, we describe recent discoveries which have increased our understanding of
      the structure and dynamics of signaling from the EGFR-family, the roles of ligand
      processing and receptor cross-talk. We discuss the relevance of these studies to
      the development of strategies for designing more effective targeted treatments
      for cancer patients.

PMID- 30098327
TI  - Oxidative stress in chronic lung disease: From mitochondrial dysfunction to
      dysregulated redox signaling.
AB  - The lung is a delicate organ with a large surface area that is continuously
      exposed to the external environment, and is therefore highly vulnerable to
      exogenous sources of oxidative stress. In addition, each of its approximately 40
      cell types can also generate reactive oxygen species (ROS), as byproducts of
      cellular metabolism and in a more regulated manner by NOX enzymes with functions
      in host defense, immune regulation, and cell proliferation or differentiation. To
      effectively regulate the biological actions of exogenous and endogenous ROS,
      various enzymatic and non-enzymatic antioxidant defense systems are present in
      all lung cell types to provide adequate protection against their injurious
      effects and to allow for appropriate ROS-mediated biological signaling. Acute and
      chronic lung diseases are commonly thought to be associated with increased
      oxidative stress, evidenced by altered cellular or extracellular redox status,
      increased irreversible oxidative modifications in proteins or DNA, mitochondrial
      dysfunction, and altered expression or activity of NOX enzymes and antioxidant
      enzyme systems. However, supplementation strategies with generic antioxidants
      have been minimally successful in prevention or treatment of lung disease, most
      likely due to their inability to distinguish between harmful and beneficial
      actions of ROS. Recent studies have attempted to identify specific redox-based
      mechanisms that may mediate chronic lung disease, such as allergic asthma or
      pulmonary fibrosis, which provide opportunities for selective redox-based
      therapeutic strategies that may be useful in treatment of these diseases.

PMID- 30098333
TI  - TUSC3 accelerates cancer growth and induces epithelial-mesenchymal transition by
      upregulating claudin-1 in non-small-cell lung cancer cells.
AB  - Lung cancer is the most frequent cause of cancer-related deaths worldwide, but
      its molecular pathogenesis is poorly understood. The tumor suppressor candidate 3
      (TUSC3) gene is located on chromosome 8p22 and is universally acknowledged as a
      cancer suppressor. However, our research has demonstrated that TUSC3 expression
      is significantly upregulated in non-small-cell lung cancer compared to benign
      controls. In this study, we analyzed the consequences of TUSC3 knockdown or
      overexpression on the biological functions of non-small-cell lung cancer cell
      lines. To identify the molecules and signaling pathways with which TUSC3 might
      interact, we completed immunoblotting, quantitative polymerase chain reaction,
      microarray, co-immunoprecipitation, and immunofluorescence assays. We
      demonstrated that TUSC3 knockdown leads to decreased proliferation, migration,
      and invasion, and reduced xenograft tumor growth of non-small-cell lung cancer
      cell lines, whereas opposite results were observed with overexpression of TUSC3.
      In addition, TUSC3 knockdown suppressed epithelial-mesenchymal transition by
      downregulating the expression of claudin-1, which plays an indispensable role in
      EMT progress. On the contrary, overexpression of TUSC3 significantly enhanced EMT
      progress by upregulating claudin-1 expression. Overall, our observations suggest
      that TUSC3 accelerates cancer growth and induces the epithelial-mesenchymal
      transition in non-small-cell lung cancer cells; we also identified claudin-1 as a
      target of TUSC3.

PMID- 30098334
TI  - MBD2-mediated Th17 differentiation in severe asthma is associated with impaired
      SOCS3 expression.
AB  - T helper 17 (Th17) cells has proven to be crucial in the pathogenesis of severe
      asthma. Although it is known that Suppressor of cytokine signaling 3 (SOCS3) is
      involved in differentiation of Th17 cells but, how it affects severe asthma is
      uncertain. Since previous studies indicated that Methtyl-CpG binding domain
      protein 2 (MBD2) null mice was deficient in Th17 cell differentiation, the aim of
      the present study was to understand how MBD2 interacts with SOCS3 to regulate
      Th17 cell differentiation in severe asthma. Here, we show that SOCS3 expression
      was significantly decreased in Th17-mediated severe asthmatic mice, accompanied
      by elevated STAT3 phosphorylation and RORgammat expression. Knock-down of SOCS3
      promoted the differentiation of naive T cells into Th17 cells through
      STAT3/RORgammat pathway. Meanwhile, MBD2 was overexpressed in Th17-mediated
      severe asthmatic mice. Intervention of MBD2 expression lead to a negative change
      of SOCS3 expression, whereas the differentiation of Th17 cells showed positive
      change. In addition, MBD2 knockout (MBD2-KO) mice displayed increased SOCS3
      expression and decreased Th17 differentiation after severe asthma modeling. Taken
      together, our results suggest that MBD2 might facilitate Th17 cell
      differentiation via down-regulating SOCS3 expression in severe asthma. These
      findings uncover new roles for SOCS3 and MBD2, and provide a potential target for
      treatment of severe asthma.

PMID- 30098335
TI  - Effects of farnesoid-X-receptor SUMOylation mutation on myocardial
      ischemia/reperfusion injury in mice.
AB  - Myocardial ischemia/reperfusion (MI/R) injury induces excessive cellular
      apoptosis and contributes significantly to final infarct size. We previously
      demonstrated that a nuclear receptor, Farnesoid X receptor (FXR), plays a crucial
      role in mediating myocardial apoptosis. The FXR functions are regulated by post
      translational modifications (PTM). However, whether the proapoptotic effect of
      FXR in MI/R injury is regulated by PTM remains unclear. Here, we aimed to study
      the effect of SUMOylation, a PTM involved in the pathogenesis of MI/R injury per
      se, on the proapoptotic effect of FXR in MI/R injury. We observed that FXR could
      be SUMOylated in heart tissues, and FXR SUMOylation levels were downregulated in
      ischemia reperfused myocardium. By overexpression of SUMOylation-defective FXR
      mutant, it was demonstrated that decreased SUMOylation augmented the detrimental
      effect of FXR, via activation of mitochondrial apoptosis pathway and autophagy
      dysfunction in MI/R injury. Further mechanistic studies suggested that decreased
      SUMOylation levels increased the transcription activity of FXR, and the
      subsequently upregulated FXR target gene SHP mediated the proapoptotic effects of
      FXR. Taken together, we provided the first evidence that the cardiac effects of
      FXR could be regulated by SUMOylation, and that manipulating FXR SUMOylation
      levels may hold therapeutic promise for constraining MI/R injury.

PMID- 30098336
TI  - Characterization of Plasmodium falciparum 6-Phosphogluconate Dehydrogenase as an
      Antimalarial Drug Target.
AB  - The enzyme 6-phosphogluconate dehydrogenase (6PGD) of the malaria parasite
      Plasmodium falciparum catalyzes the third step of the pentose phosphate pathway
      converting 6-phosphogluconate (6PG) to ribulose 5-phosphate. The NADPH produced
      by 6PGD is crucial for antioxidant defense and redox regulation, and ribose 5
      phosphate is essential for DNA and RNA synthesis in the rapidly growing parasite.
      Thus, 6PGD represents an attractive antimalarial drug target. In this study, we
      present the X-ray structures of Pf6PGD in native form as well as in complex with
      6PG or nicotinamide adenine dinucleotide phosphate (NADP+) at resolutions of 2.8,
      1.9, and 2.9 A, respectively. The overall structure of the protein is similar to
      structures of 6PGDs from other species; however, a flexible loop close to the
      active site rearranges upon binding of 6PG and likely regulates the conformation
      of the cofactor NADP+. Upon binding of 6PG, the active site loop adopts a closed
      conformation. In the absence of 6PG, the loop opens and NADP+ is bound in a
      waiting position, indicating that the cofactor and 6PG bind independently from
      each other. This sequential binding mechanism was supported by kinetic studies on
      the homodimeric wild-type Pf6PGD. Furthermore, the function of the Plasmodium
      specific residue W104L mutant was characterized by site-directed mutagenesis.
      Notably, the activity of Pf6PGD was found to be post-translationally redox
      regulated via S-nitrosylation, and screening the Medicines for Malaria Venture
      Malaria Box identified several compounds with IC50s in the low micromolar range.
      Together with the three-dimensional structure of the protein, this is a promising
      starting point for further drug discovery approaches.

PMID- 30098337
TI  - Quinolinic Acid Amyloid-like Fibrillar Assemblies Seed alpha-Synuclein
      Aggregation.
AB  - Quinolinic acid (QA), a downstream neurometabolite in the kynurenine pathway, the
      biosynthetic pathway of tryptophan, is associated with neurodegenerative diseases
      pathology. Mutations in genes encoding kynurenine pathway enzymes, which control
      the level of QA production, are linked with elevated risk of developing
      Parkinson's disease. Recent findings have revealed the accumulation and
      deposition of QA in post-mortem samples, as well as in cellular models of
      Alzheimer's disease and related disorders. Furthermore, intrastriatal inoculation
      of mice with QA results in increased levels of phosphorylated alpha-synuclein and
      neurodegenerative pathological and behavioral characteristics. However, the
      cellular and molecular mechanisms underlying the involvement of QA accumulation
      in protein aggregation and neurodegeneration remain elusive. We recently
      established that self-assembled ordered structures are formed by various
      metabolites and hypothesized that these "metabolite amyloids" may seed
      amyloidogenic proteins. Here we demonstrate the formation of QA amyloid-like
      fibrillar assemblies and seeding of alpha-synuclein aggregation by these
      nanostructures both in vitro and in cell culture. Notably, alpha-synuclein
      aggregation kinetics was accelerated by an order of magnitude. Additional amyloid
      like properties of QA assemblies were demonstrated using thioflavin T assay,
      powder X-ray diffraction and cell apoptosis analysis. Moreover, fluorescently
      labeled QA assemblies were internalized by neuronal cells and co-localized with
      alpha-synuclein aggregates. In addition, we observed cell-to-cell propagation of
      fluorescently labeled QA assemblies in a co-culture of treated and untreated
      cells. Our findings suggest that excess QA levels, due to mutations in the
      kynurenine pathway, for example, may lead to the formation of metabolite
      assemblies that seed alpha-synuclein aggregation, resulting in neuronal toxicity
      and induction of Parkinson's disease.

PMID- 30098339
TI  - Characterization of Denatured States and Reversible Unfolding of Sensory
      Rhodopsin II.
AB  - Our understanding on the folding of membrane proteins lags behind that of soluble
      proteins due to challenges posed by the exposure of hydrophobic regions during in
      vitro chemical denaturation and refolding experiments. While different folding
      models are accepted for soluble proteins, only the two-stage model and the long
      range interactions model have been proposed so far for helical membrane proteins.
      To address our knowledge gap on how different membrane proteins traverse their
      folding pathways, we have systematically investigated the structural features of
      SDS-denatured states and the kinetics for reversible unfolding of sensory
      rhodopsin II (pSRII), a retinal-binding photophobic receptor from Natronomonas
      pharaonis. pSRII is difficult to denature, and only SDS can dislodge the retinal
      chromophore without rapid aggregation. Even in 30% SDS (0.998 ChiSDS), pSRII
      retains the equivalent of six out of seven transmembrane helices, while the
      retinal-binding pocket is disrupted, with transmembrane residues becoming more
      solvent exposed. Folding of pSRII from an SDS-denatured state harboring a
      covalently bound retinal chromophore shows deviations from an apparent two-state
      behavior. SDS denaturation to form the sensory opsin apo-protein is reversible.
      We report pSRII as a new model protein which is suitable for membrane protein
      folding studies and has a unique folding mechanism that differs from those of
      bacteriorhodopsin and bovine rhodopsin.

PMID- 30098338
TI  - Temporal and Spatial Epigenome Editing Allows Precise Gene Regulation in
      Mammalian Cells.
AB  - Cell-type specific gene expression programs are tightly linked to epigenetic
      modifications on DNA and histone proteins. Here, we used a novel CRISPR-based
      epigenome editing approach to control gene expression spatially and temporally.
      We show that targeting dCas9-p300 complex to distal non-regulatory genomic
      regions reprograms the chromatin state of these regions into enhancer-like
      elements. Notably, through controlling the spatial distance of these induced
      enhancers (i-Enhancer) to the promoter, the gene expression amplitude can be
      tightly regulated. To better control the temporal persistence of induced gene
      expression, we integrated the auxin-inducible degron technology with CRISPR
      tools. This approach allows rapid depletion of the dCas9-fused epigenome modifier
      complex from the target site and enables temporal control over gene expression
      regulation. Using this tool, we investigated the temporal persistence of a
      locally edited epigenetic mark and its functional consequences. The tools and
      approaches presented here will allow novel insights into the mechanism of
      epigenetic memory and gene regulation from distal regulatory sites.

PMID- 30098340
TI  - Molecular Highways-Navigating Collisions of DNA Motor Proteins.
AB  - Fundamental biological processes require concurrent sharing of DNA by numerous
      motor proteins and complexes. Thus, collision, congestion, and roadblocks are
      inescapable on these busy "molecular highways." The consequences of these traffic
      problems are diverse, resulting in complex cellular mechanisms to resolve threats
      to genome stability and ensure cellular viability. Here, we review the different
      types of events and the diverse consequences that an RNA polymerase may encounter
      during transcription. We also address advances in the field that facilitate in
      depth investigation of intrinsic motor properties and multi-protein interactions
      and coordination, which are necessary to understand these complicated
      interactions. Together, these results provide mechanistic insights into how RNA
      polymerase successfully navigates its passage through crowded molecular highways.

PMID- 30098342
TI  - Important roles of the Ca2+-sensing receptor in vascular health and disease.
AB  - Ca2+-sensing receptor (CaSR), a member of G protein-coupled receptor family, is
      widely expressed in the vascular system, including perivascular neurons, vascular
      endothelial cells (VECs) and vascular smooth muscle cells (VSMCs). When
      stimulated, CaSR can further increase the cytosolic Ca2+ concentration
      ([Ca2+]cyt) in two ways: intracellular Ca2+ release from endo/sarcoplasmic
      reticulum (ER/SR) and extracellular Ca2+ entry through Ca2+-permeable cation
      channels. In endothelium, increased Ca2+ subsequently activate nitric oxide
      synthase (NOS) and intermediate conductance Ca2+-activated K+ channels (IKCa),
      resulting in vasodilation through NOS-mediated NO release or membrane
      hyperpolarization. In VSMCs, CaSR-induced intracellular Ca2+ increase causes
      blood vessel constriction. CaSR activation predominantly induces vasorelaxation
      of whole vascular tissues through VECs-dependent mechanisms; however, CaSR
      induced Ca2+ signaling in VSMCs may play a braking role in CaSR-mediated
      vasorelaxation. Emerging evidence reveals the importance of CaSR in the
      regulation of vascular tone and blood pressure. Here, we summarized recent
      advances in CaSR-mediated vascular reaction and the underlying mechanisms in
      different species, including humans. In addition, several studies have
      demonstrated that CaSR dysfunction may be associated with some fatal vascular
      diseases, such as pulmonary arterial hypertension, primary hypertension,
      diabetes, acute myocardial infarction and vascular calcification. With the
      advance of studies on CaSR in vascular health and disease, it is expected
      positive modulators or negative modulators of CaSR used for the treatment of
      specific diseases may be promising therapeutic options for the prevention and/or
      treatment of vascular diseases.

PMID- 30098343
TI  - Regulation of blood pressure is influenced by gender: A study in obese Zucker
      rats.
AB  - AIM: The present study determined the role of renin-angiotensin system (RAS),
      endothelin system, and eicosanoid system in the blood pressure (BP) regulation in
      male and female Zucker rats, and whether the pressor response change similarly in
      lean and obese animals. MATERIAL AND METHODS: In female (f) and male (m), lean
      (L) and obese (O) Zucker rats (ZR) at 22 weeks old, we evaluated the role of the
      3 mentioned systems using the following treatments: 1) enalapril (angiotensin I
      converting enzyme inhibitor), 2) the ABT-627 (endothelin receptor A (ETA)
      antagonist), and 3) the 1-aminobenzotriazol (1-ABT: eicosanoid synthesis
      inhibitor). KEY FINDINGS: MAP by radiotelemetry was similar and significantly
      higher in mOZR (120 +/- 2 mm Hg) and fOZR (116 +/- 4 mm Hg) (p < 0.05 vs. m-,
      fLZR), than mLZR (105 +/- 3 mm Hg) and fLZR (106 +/- 1 mm Hg), that were also
      similar. Enalapril reduced MAP more in mOZR (23%) and mLZR (26%), than fLZR (20%,
      p < 0.905 vs. mLZR) or fOZR (9%; p < 0.05 vs. other groups). After 10 days of
      drug-free and recovery period, ABT-627 reduced MAP in fLZR and mLZR by similar
      amounts (102 +/- 4 to 92 +/- 3 mm Hg, n = 6; p < 0.05 and 105 +/- 2 vs. 92 +/- 3
      mm Hg, n = 6; p < 0.05, respectively), but did not affect either fOZR or mOZR.
      After another 10 days of drug-free and recovery period, 1-ABT reduced MAP in fOZR
      (116 +/- 4 to 95 +/- 2, n = 6; p < 0.05), and did not affect all other groups.
      SIGNIFICANCE: We show that the mechanisms responsible for elevated BP in male and
      female OZR and LZR are different, and suggest that obesity may cause an increase
      in BP via different mechanisms in men and women as well.

PMID- 30098341
TI  - Functional Amyloid and Other Protein Fibers in the Biofilm Matrix.
AB  - Biofilms are ubiquitous in the natural and man-made environment. They are defined
      as microbes that are encapsulated in an extracellular, self-produced, biofilm
      matrix. Growing evidence from the genetic and biochemical analysis of single
      species biofilms has linked the presence of fibrous proteins to a functional
      biofilm matrix. Some of these fibers have been described as functional amyloid or
      amyloid-like fibers. Here we provide an overview of the biophysical and
      biological data for a wide range of protein fibers found in the biofilm matrix of
      Gram-positive and Gram-negative bacteria.

PMID- 30098346
TI  - Advanced Optical Coherence Tomography Angiography Analysis of Age-related Macular
      Degeneration Complicated by Onset of Unilateral Choroidal Neovascularization.
AB  - PURPOSE: To analyze optical coherence tomography angiography (OCTA) quantitative
      features in patients affected by new-onset choroidal neovascularization (CNV) in
      1 eye and early/intermediate age-related macular degeneration (AMD) in the fellow
      eye. DESIGN: Case-control study. METHODS: Setting: Clinical practice. STUDY
      POPULATION: Thirty patients and 30 age-matched controls. OBSERVATION PROCEDURES:
      Both cohorts underwent complete ophthalmologic examination, including best
      corrected visual acuity (BCVA) measurement, biomicroscopy, fluorescein
      angiography (FA) and indocyanine green angiography (ICGA) examination, optical
      coherence tomography, and OCTA scans. The 1-way a test with Bonferroni correction
      was used to assess statistical significance and Tau Kendall's correlation
      analysis was performed. MAIN OUTCOME MEASURES: BCVA, choroidal thickness, vessel
      density, vessel tortuosity, vessel dispersion. and vessel rarefaction. RESULTS:
      Mean BCVA was 20/32 for CNV eyes and 20/20 for both fellow and control eyes.
      Choroidal thickness was 190.33 +/- 63.98 MUm for CNV eyes, 216.83 +/- 50.31 MUm
      for fellow eyes, and 310.52 +/- 27.13 MUm for controls. The quantitative analysis
      of retinal vessels revealed significant alterations, especially in the deep
      capillary plexus and radial peripapillary capillaries, both in CNV and in fellow
      eyes, compared with controls. In particular, decreased vessel density and
      tortuosity and increased dispersion and rarefaction were found. Several
      significant correlations were also found among the quantitative parameters
      adopted. CONCLUSIONS: New postprocessing OCTA parameters are able to detect deep
      retinal vascular alterations quantitatively, in both CNV-affected and fellow eyes
      of patients with new-onset CNV. Further investigations are warranted in order to
      explore the validity of these new approaches on follow-up.

PMID- 30098344
TI  - Clinical significance and functions of microRNA-93/CDKN1A axis in human cervical
      cancer.
AB  - AIM: Accumulating studies have revealed that microRNA (miR)-93 may exert an
      oncogenic role in various cancers via inhibiting CDKN1A. However, the involvement
      of miR-93/CDKN1A axis in cervical cancer remains unclear. We aimed to investigate
      expression pattern, clinical significance and potential functions of miR
      93/CDKN1A axis in cervical cancer. METHODS: Expression levels of miR-93 and
      CDKN1A mRNA in 100 pairs of cervical cancer and matched non-cancerous tissue
      samples were detected by quantitative-PCR. Statistical analyses were performed to
      evaluate associations of miR-93 and/or CDKN1A expression with various
      clinicopathologic features and patients' prognosis. The functions of miR
      93/CDKN1A axis on cell proliferation and invasion were also examined. RESULTS:
      Compared to non-cancerous tissues, the expression levels of miR-93 and CDKN1A
      were dramatically increased and decreased in cervical cancer tissues,
      respectively (both P < 0.01). High miR-93 and/or low CDKN1A expression were
      significantly associated with advanced International Federation of Gynecology and
      Obstetrics stage, the presence of lymph node metastasis and recurrence (all P <
      0.05). Importantly, patients with high miR-93 and/or low CDKN1A expression had
      shorter overall survival than those with low miR-93 and/or high CDKN1A
      expression. The multivariate analysis identified miR-93 and/or CDKN1A expression
      as independent prognostic factors of cervical cancer. Functionally, miR-93
      promoted cell proliferation and invasion of cervical cancer cells via inhibiting
      CDKN1A. CONCLUSION: miR-93 upregulation and CDKN1A downregulation may be both
      associated with the development, progression and patients' prognosis of cervical
      cancer. miR-93/CDKN1A axis may also play an important role in the malignancy of
      cervical cancer cells, suggesting its potential as a therapeutic target for this
      cancer.

PMID- 30098345
TI  - Spectral-Domain Optical Coherence Tomography of the Vitreopapillary Interface in
      Acute Nonarteritic Anterior Ischemic Optic Neuropathy.
AB  - PURPOSE: To use spectral-domain optical coherence tomography (SD-OCT) to assess
      whether epipapillary vitreous traction from evolving posterior vitreous
      detachment (PVD) is mechanistically involved in the pathogenesis of nonarteritic
      anterior ischemic optic neuropathy (NAION). DESIGN: Retrospective cohort study.
      METHODS: Setting: Single academic center. Patient or Study Population: Eighty
      eyes in 74 subjects presenting within 2 weeks of symptom onset of NAION.
      Intervention or Observation Procedures: SD-OCT imaging of the optic nerve head,
      macula, and peripapillary retinal nerve fiber layer (pRNFL) were reviewed for PVD
      and vitreopapillary traction (VPT). MAIN OUTCOME MEASURES: Prevalence and
      incidence of PVD and VPT, logMAR best-corrected visual acuity (BCVA), mean
      deviation (MD) on automated perimetry, and pRNFL thickness at presentation and
      final follow-up. RESULTS: The co-prevalence of PVD at the time of acute
      presentation for NAION was 30% (n = 24/80). This was similar to the prevalence of
      PVD in contralateral uninvolved eyes (34.5%, n = 19/55). In 8 NAION eyes, PVD had
      been documented prior to the onset of NAION. No eyes had SD-OCT evidence of VPT
      on presentation or final follow-up. Only 5 eyes developed a PVD following the
      development of NAION, and this typically occurred months after resolution of
      optic disc edema. When comparing eyes with PVD and without PVD, there was no
      significant difference in BCVA, MD, and pRNFL thickness at baseline, final follow
      up, or the change from baseline to final follow-up (all P > .10). CONCLUSIONS:
      VPT was not mechanistically related to the development of classic NAION.
      Preexisting PVD did not preclude the future development of NAION. The co
      prevalence of PVD with acute NAION had no impact on final visual outcome.

PMID- 30098347
TI  - Comparing Outcomes of Phacoemulsification With Femtosecond Laser-Assisted
      Cataract Surgery in Patients With Fuchs Endothelial Dystrophy.
AB  - PURPOSE: To compare the outcome in patients with Fuchs endothelial dystrophy
      (FED) who underwent standard phacoemulsification vs femtosecond laser-assisted
      cataract surgery (FLACS) in the treatment of visually significant cataracts.
      DESIGN: Retrospective, comparative, interventional case series. METHODS: Patient
      or Study Population: Between April 2013 and December 2016, 140 FED eyes with
      cataracts of all densities were included. Seventy-two eyes underwent
      phacoemulsification and 68 eyes underwent FLACS. Intervention or Observation
      Procedures: Automated noncontact specular microscopy was performed at baseline
      and postoperatively over a mean of 17.91 +/- 10.47 months. Parameters collected
      include visual acuity, slit-lamp examination findings, and intraoperative
      findings. MAIN OUTCOME MEASURES: Pachymetry, endothelial cell density (ECD), and
      coefficient of variance (COV) were compared. RESULTS: Phacoemulsification had
      significantly greater postoperative median loss of ECD of 229.0 cells/mm2 (14.2%)
      compared to FLACS ECD of 133.0 cells/mm2 (6.5%) (U = 1343.0, Z = -2.241, P =
      .025). Mean loss of ECD was 346.524 +/- 420.472 cells/mm2 and 119.964 +/- 434.882
      cells/mm2 for phacoemulsification and FLACS, respectively (P = .005). Mean
      percentage loss of ECD was 15.3% +/- 17.5% for phacoemulsification and 4.4% +/-
      25.0% for FLACS (P = .006). Eyes that underwent phacoemulsification had 10.7% +/-
      15.4% mean ECD loss in the mild cataract group, and in the moderate/hard cataract
      group 19.5% +/- 18.0%, P = .045. Eyes that underwent FLACS had 0.9% +/- 22.5%
      mean ECD loss in the mild cataract group, and 8.2% +/- 26.3% in the moderate/hard
      cataract group, P = .291. Comparison between procedures of mean ECD loss for
      moderate/hard cataracts was significant (P = .043). CONCLUSIONS: FLACS is shown
      to be superior to phacoemulsification in reducing postoperative endothelial cell
      loss in FED patients, which translates to a lower risk of corneal decompensation,
      especially in patients with moderate/hard cataract densities.

PMID- 30098348
TI  - Enhanced Tomographic Assessment to Detect Corneal Ectasia Based on Artificial
      Intelligence.
AB  - PURPOSE: To improve the detection of corneal ectasia susceptibility using
      tomographic data. DESIGN: Multicenter case-control study. METHODS: Data from
      patients from 5 different clinics from South America, the United States, and
      Europe were evaluated. Artificial intelligence (AI) models were generated using
      Pentacam HR (Oculus, Wetzlar, Germany) parameters to discriminate the
      preoperative data of 3 groups: stable laser-assisted in situ keratomileusis
      (LASIK) cases (2980 patients with minimum follow-up of 7 years), ectasia
      susceptibility (71 eyes of 45 patients that developed post-LASIK ectasia [PLE]),
      and clinical keratoconus (KC; 182 patients). Model accuracy was independently
      tested in a different set of stable LASIK cases (298 patients with minimum follow
      up of 4 years) and in 188 unoperated patients with very asymmetric ectasia (VAE);
      these patients presented normal topography (VAE-NT) in 1 eye and clinically
      diagnosed ectasia in the other (VAE-E). Accuracy was evaluated with ROC curves.
      RESULTS: The random forest (RF) provided highest accuracy among AI models in this
      sample with 100% sensitivity for clinical ectasia (KC+VAE-E; cutoff 0.52), being
      named Pentacam Random Forest Index (PRFI). Considering all cases, the PRFI had an
      area under the curve (AUC) of 0.992 (94.2% sensitivity, 98.8% specificity; cutoff
      0.216), being statistically higher than the Belin/Ambrosio deviation (BAD-D; AUC
      = 0.960, 87.3% sensitivity, 97.5% specificity; P = .006, DeLong's test). The
      optimized cutoff of 0.125 provided sensitivity of 85.2% for VAE-NT and 80% for
      PLE, with 96.6% specificity. CONCLUSION: The PRFI enhances ectasia diagnosis.
      Further integrations with corneal biomechanical parameters and with the corneal
      impact from laser vision correction are needed for assessing ectasia risk.

PMID- 30098349
TI  - Anomalous Vertical Deviations in Attempted Abduction Occur in the Majority of
      Patients With Esotropic Duane Syndrome.
AB  - PURPOSE: To describe a phenomenon, depression in attempted abduction, not
      previously recognized as a feature of Duane syndrome (DS). DESIGN: Retrospective,
      observational case series. METHODS: Setting: Institutional practice. PATIENT
      POPULATION: Patients diagnosed with esotropic DS at Boston Children's Hospital
      from 2002 to 2015. Patients with clinical photographs documenting horizontal gaze
      were included. Patients with prior strabismus surgery were excluded. OBSERVATION
      PROCEDURES: Patients were classified into 3 groups according to their vertical
      eye position in attempted abduction: midline group, depression group, and
      elevation group. Group assignment was performed by 3 independent
      ophthalmologists. Baseline characteristics, eye movement, and ocular deviation
      were compared among the 3 groups. MAIN OUTCOME MEASURES: Horizontal and vertical
      deviation on attempted abduction in the DS eye. RESULTS: Depression in attempted
      abduction was present in 74 of 113 unilateral patients (66%) and 18 of 42
      gradable eyes (43%) of bilateral patients. Abduction limitation was significantly
      less severe in the midline group (median: -3.0) than in the depression group
      (median: -4.0) (P = .01). Vertical deviation in attempted abduction was more
      severe in the elevation group than in the depression group (P = .003).
      CONCLUSIONS: Depression of the eye in attempted abduction has not been widely
      described, yet it is present in the majority of DS patients. It is more likely to
      occur with more severe abduction limitation. This phenomenon is likely another
      form of dysinnervation in DS, the result either of anomalous vertical rectus
      muscle activation or asymmetric lateral rectus muscle innervation during
      attempted abduction. Awareness of vertical deviation in attempted abduction may
      facilitate surgical planning in affected patients.

PMID- 30098350
TI  - Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema in a
      Real-World Clinical Setting.
AB  - PURPOSE: To report the long-term outcomes of intravitreal anti-vascular
      endothelial growth factor (VEGF) treatment for diabetic macular edema (DME) in a
      real-world clinical setting and to assess the efficacy of subsequent alternative
      treatments in eyes with suboptimal response to anti-VEGF. DESIGN: Retrospective
      interventional case series. METHODS: The medical records of consecutive eyes with
      center-involving DME, treated between August 2008 and June 2015 with 3 monthly
      intravitreal anti-VEGF injections-with or without prompt or deferred laser
      followed by pro re nata re-treatment, were reviewed. A subgroup of eyes that were
      unresponsive to the treatment received subsequent alternative therapeutic
      options, including switching to another anti-VEGF drug, intravitreal injection of
      dexamethasone, and vitrectomy. RESULTS: A total of 170 eyes of 129 patients were
      included in the study. The mean follow-up (FU) was 45.6 months (SD 18; minimum 12
      maximum 81). The change in mean best-corrected visual acuity (BCVA) at 1-year FU
      was +5 ETDRS letters (P < .0001). Improvement in BCVA was statistically
      significant up to 5 years. Improvement in central macular thickness (CMT) was
      statistically significant up to the last FU visit. In eyes with suboptimal
      response, no significant visual improvement was found by switching to another
      anti-VEGF (P =.4347). Twenty-four eyes treated with intravitreal dexamethasone
      and 14 with vitrectomy exhibited a significant reduction in CMT with variable
      functional responses. In these eyes, better BCVA gain was found in cases with an
      early change of the treatment strategy. CONCLUSION: The results support treatment
      with intravitreal anti-VEGF for DME in real-world clinical settings and suggest
      that an early change of the therapeutic strategy should be considered for eyes
      unresponsive to the treatment.

PMID- 30098351
TI  - The Asia Cornea Society Infectious Keratitis Study: A Prospective Multicenter
      Study of Infectious Keratitis in Asia.
AB  - PURPOSE: To survey the demographics, risk factors, microbiology, and outcomes for
      infectious keratitis in Asia. DESIGN: Prospective, nonrandomized clinical study.
      METHODS: Thirteen study centers and 30 sub-centers recruited consecutive subjects
      over 12-18 months, and performed standardized data collection. A microbiological
      protocol standardized the processing and reporting of all isolates. Treatment of
      the infectious keratitis was decided by the managing ophthalmologist. Subjects
      were observed for up to 6 months. Main outcome measures were final visual acuity
      and the need for surgery during infection. RESULTS: A total of 6626 eyes of 6563
      subjects were studied. The majority of subjects were male (n = 3992). Trauma (n =
      2279, 34.7%) and contact lens wear (n = 704, 10.7%) were the commonest risk
      factors. Overall, bacterial keratitis was diagnosed in 2521 eyes (38.0%) and
      fungal keratitis in 2166 eyes (32.7%). Of the 2831 microorganisms isolated, the
      most common were Fusarium species (n = 518, 18.3%), Pseudomonas aeruginosa (n =
      302, 10.7%), and Aspergillus flavus (n = 236, 8.3%). Cornea transplantation was
      performed in 628 eyes to manage ongoing infection, but 289 grafts (46%) had
      failed by the end of the study. Moderate visual impairment (Snellen vision less
      than 20/60) was documented in 3478 eyes (53.6%). CONCLUSION: Demographic and risk
      factors for infection vary by country, but infections occur predominantly in male
      subjects and are frequently related to trauma. Overall, a similar percentage of
      bacterial and fungal infections were diagnosed in this study. Visual recovery
      after infectious keratitis is guarded, and corneal transplantation for active
      infection is associated with a high failure rate.

PMID- 30098352
TI  - Efficacy of Cataract Surgery With Trabecular Microbypass Stent Implantation in
      Combined-Mechanism Angle Closure Glaucoma Patients.
AB  - PURPOSE: To evaluate the effectiveness of trabecular microbypass stent (iStent)
      implantation in combined mechanism glaucoma (CMG). DESIGN: Retrospective cohort
      study. METHODS: We reviewed the medical charts of patients with the following
      scenarios: (1) primary open-angle glaucoma (POAG) undergoing phacoemulsification
      (PE), (2) POAG undergoing PE with iStent (POAG-PE/iStent), (3) CMG undergoing PE
      (CMG-PE), and (4) CMG undergoing PE with iStent (CMG-PE/iStent). CMG was defined
      as narrow-angle glaucoma patients whose angle had opened after iridotomy. Linear
      mixed-effects models were performed to determine the effect of iStent on
      postoperative 1-year success rate (intraocular pressure [IOP] <= 18 without
      medication), IOP, and number of medications. RESULTS: Data from 301 eyes were
      available. The number of eyes (subjects) was 61 (45) in the POAG-PE, 60 (50) in
      POAG-PE/iStent, 93 (76) in CMG-PE, and 87 (70) in CMG-PE/iStent group. Success
      criteria were achieved in 13.1% for POAG-PE, 33.3% for POAG-PE/iStent (POAG-PE vs
      POAG-PE/iStent B 3.01; P < .001), 37.6% for CMG-PE, and 43.7% for CMG-PE/iStent
      (CMG-PE vs CMG-PE/iStent B 2.25; P < .001). There was no difference in the IOP
      between POAG-PE and POAG-PE/iStent, and between CMG-PE and CMG-PE/iStent. The
      iStent significantly reduced number of medications in the POAG (B -0.70; P <
      .001) and CMG group (B -0.52; P < .001). Comparing the effect of iStent on POAG
      and CMG, the analysis showed similar iStent efficacy in terms of the success
      rate, IOP, and number of medications (P > .05). CONCLUSIONS: Combined PE/iStent
      significantly increased success rate and reduced number of medications in CMG
      patients compared to PE alone. The effects of iStent were comparable between POAG
      and CMG groups.

PMID- 30098354
TI  - The Phenotypic Spectrum of Albinism.
AB  - PURPOSE: To describe the phenotypic spectrum of a large cohort of albino
      patients, to investigate the relationship between the ocular abnormalities and
      the visual acuity (VA), and to define diagnostic criteria for the white
      population. We also estimated the prevalence of albinism in The Netherlands.
      DESIGN: Retrospective cohort study. PARTICIPANTS: We investigated the phenotype
      of 522 patients with albinism from the databases of Bartimeus (452 patients),
      Leiden University Medical Center (44 patients), and the Academic Medical Center
      Amsterdam (26 patients). METHODS: We collected clinical, genetic, and
      electrophysiologic data of patients with albinism. We used grading schemes for
      iris translucency, fundus hypopigmentation, and foveal hypoplasia. MAIN OUTCOME
      MEASURES: Visual acuity, nystagmus, iris translucency, fundus pigmentation,
      foveal hypoplasia, and misrouting. RESULTS: Nystagmus was absent in 7.7%
      (40/521), iris translucency could not be detected in 8.9% (44/492), 3.8% (19/496)
      had completely normal fundus pigmentation, 0.7% (3/455) had no foveal hypoplasia,
      and misrouting was not established in 16.1% (49/304). The VA varied from -0.1 to
      1.3 logarithm of the minimum of angle of resolution (logMAR). The foveal
      hypoplasia grading correlated best with the VA (r = 0.69, P < 0.001), whereas
      iris translucency, fundus pigmentation, and misrouting did not predict the VA
      significantly. We estimated a prevalence of albinism in The Netherlands of at
      least 1:12 000. CONCLUSIONS: None of the characteristics of albinism were
      consistently present in our cohort. To be able to distinguish albinism from other
      conditions with similar ocular features, especially in northern and western
      European countries, we propose major and minor clinical criteria. Major criteria
      would be (1) foveal hypoplasia grade 2 or more, (2) misrouting, and (3) ocular
      hypopigmentation, either iris translucency or fundus hypopigmentation grade 2 or
      more. Minor criteria would be (1) nystagmus, (2) hypopigmentation of skin and
      hair, (3) grade 1 fundus hypopigmentation, and (4) foveal hypoplasia grade 1. We
      propose that 3 major criteria or 2 major and 2 minor criteria are necessary for
      the diagnosis. In the presence of a molecular diagnosis, 1 major criterion or 2
      minor criteria will be sufficient.

PMID- 30098356
TI  - Mode of action of piperovatine, an insecticidal piperamide isolated from Piper
      piscatorum (Piperaceae), against voltage-gated sodium channels.
AB  - Piperamides, which are secondary metabolites in the genus Piper, have potent
      insecticidal activity, and have thus inspired the development of novel
      insecticides. In this study, piperovatine, a piperamide from Piper piscatorum
      (Piperaceae), was investigated using a two-electrode voltage clamp to clarify its
      detailed mode of action against voltage-gated sodium channels, a classic target.
      In Xenopus oocytes expressing voltage-gated sodium channels from German cockroach
      (Blattella germanica), piperovatine induced inward currents depending on
      repetitive openings. For instance, maximal currents were generated with 10 MUM
      piperovatine following 100 trains of depolarizing pulses with frequency 25 Hz.
      Piperovatine also shifted the half-activation voltage after conditioning pulses
      from -35 mV to -45 mV. In addition, piperovatine-modified currents were
      correlated with not only the number of prior conditioning pulses but also the
      proportion of activated channels. Finally, piperovatine was found to stabilize
      voltage-gated sodium channels in the fast-inactivated state after opening, and
      inhibit transition to the slow-inactivated state. These results suggest that
      piperovatine preferably binds to activated channels and stabilizes voltage
      sensors at the conformation acquired during depolarization.

PMID- 30098355
TI  - Intermittent low-level lead exposure provokes anxiety, hypertension, autonomic
      dysfunction and neuroinflammation.
AB  - BACKGROUND: Exposures to lead (Pb) during developmental phases can alter the
      normal course of development, with lifelong health consequences. Permanent Pb
      exposure leads to behavioral changes, cognitive impairment, sympathoexcitation,
      tachycardia, hypertension and autonomic dysfunction. However, the effects of an
      intermittent lead exposure are not yet studied. This pattern of exposure has been
      recently increasing due to migrations, implementation of school exchange programs
      and/or residential changes. OBJECTIVE: To determine and compare lead effects on
      mammal's behavior and physiology, using a rat model of intermittent and permanent
      Pb exposures. METHODS: Fetuses were intermittently (PbI) or permanently (PbP)
      exposed to water containing lead acetate (0.2% w/v) throughout life until
      adulthood (28 weeks of age). A control group (CTL) without any exposure to lead
      was also used. Anxiety was assessed by elevated plus maze (EPM) and locomotor
      activity and exploration by open field test (OFT). Blood pressure (BP),
      electrocardiogram (ECG), heart rate (HR), respiratory frequency (RF), sympathetic
      and parasympathetic activity and baro- and chemoreceptor reflex profiles were
      evaluated. Immunohistochemistry protocol for the assessment of neuroinflammation,
      neuronal loss (NeuN), gliosis and synaptic alterations (Iba-1, GFAP, Syn), were
      performed at the hippocampus. One-way ANOVA with Tukey's multiple comparison
      between means were used (significance p < 0.05) for statistical analysis.
      RESULTS: The intermittent lead exposure produced a significant increase in
      diastolic and mean BP values, concomitant with a tendency to sympathetic
      overactivity (estimated by increased low-frequency power) and without significant
      changes in systolic BP, HR and RF. A chemoreceptor hypersensitivity and a
      baroreflex impairment were also observed, however, less pronounced when compared
      to the permanent exposure. Regarding behavioral changes, both lead exposure
      profiles showed an anxiety-like behavior without changes in locomotor and
      exploratory activity. Increase in GFAP and Iba-1 positive cells, without changes
      in NeuN positive cells were found in both exposed groups. Syn staining suffered a
      significant decrease in PbI group and a significant increase in PbP group.
      CONCLUSION: This study is the first to show that developmental Pb exposure since
      fetal period can cause lasting impairments in physiological parameters. The
      intermittent lead exposure causes adverse health effects, i.e, hypertension,
      increased respiratory frequency and chemoreflex sensitivity, baroreflex
      impairment, anxiety, decreased synaptic activity, neuroinflammation and reactive
      gliosis, in some ways similar to a permanent exposure, however some are lower
      grade, due to the shorter duration of exposure. This study brings new insights on
      the environmental factors that influence autonomic and cardiovascular systems
      during development, which can help in creating public policy strategies to
      prevent and control the adverse effects of Pb toxicity.

PMID- 30098353
TI  - Donor, Recipient, and Operative Factors Associated with Graft Success in the
      Cornea Preservation Time Study.
AB  - PURPOSE: To associate donor, recipient, and operative factors with graft success
      3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in
      the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a
      multicenter, double-masked, randomized clinical trial. PARTICIPANTS: One thousand
      ninety individuals (1330 study eyes) with a median age of 70 years undergoing
      DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or
      aphakic corneal edema (PACE; 6% of eyes). METHODS: Eyes undergoing DSAEK were
      randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days
      (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters
      were recorded prospectively. Graft failure was defined as regraft for any reason,
      a graft that failed to clear by 8 weeks after surgery, or an initially clear
      graft that became and remained cloudy for 90 days. Failure in the first 8 weeks
      was classified further as primary donor failure or early failure, in the absence
      or presence of operative complications, respectively. Proportional hazards and
      logistic regression models were used to estimate risk ratios (RR) and 99%
      confidence intervals (CIs) for graft failure. MAIN OUTCOME MEASURES: Graft
      success at 3 years. RESULTS: One thousand two hundred fifty-one of 1330 grafts
      (94%) remained clear at 3 years and were considered successful. After adjusting
      for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and
      operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with
      increased risk for primary or early failure. Preoperative diagnosis of PACE (RR,
      3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by
      3 years after surgery compared with Fuchs dystrophy. Graft success showed little
      variation among other factors evaluated, including donor age (RR, 1.19 per
      decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell
      density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter
      (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft
      insertion (RR, 0.92; 99% CI, 0.40-2.10). CONCLUSIONS: Descemet stripping
      automated endothelial keratoplasty success in the early and entire postoperative
      period is more likely when the donor did not have diabetes and was without
      operative complications and in the long-term postoperative period in recipients
      with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic
      donors and PACE recipients reduce the rate of graft success after DSAEK warrant
      further study.

PMID- 30098357
TI  - Structure and inflammatory activity of the LPS isolated from Acetobacter
      pasteurianus CIP103108.
AB  - Acetobacter pasteurianus is an acetic acid-producing Gram-negative bacterium
      commonly found associated with plants and plant products and widely used in the
      production of fermented foods, such as kefir and vinegar. Due to the acid
      conditions of the bacterium living habitat, uncommon structural features
      composing its cell envelope are expected. In the present work we have
      investigated the A. pasteurianus CIP103108 lipopolysaccharide (LPS) structure and
      immunoactivity. The structure of the lipid A and of two different O
      polysaccharides was assessed. Furthermore, immunological studies with human cells
      showed a low immunostimulant activity of the isolated LPS, in addition to a
      slight capability to lower the NF-kB activation upon stimulation by toxic LPS.

PMID- 30098358
TI  - Nanoimmobilization of beta-glucosidase onto hydroxyapatite.
AB  - beta-Glucosidase is an enzyme of great industrial interest that is used in
      biorefineries and in the pharmaceutical, food, and beverage sectors, among
      others. These industrial processes would benefit from the use of immobilized
      enzyme systems that allow several reuses of the enzyme. A promising inorganic and
      nontoxic material for such application is hydroxyapatite (HA), which can be
      synthesized at nanometric scale, hence providing good accessibility of the
      substrate to the catalyst. Here, we carried out a systematic study to evaluate
      the feasibility of immobilizing beta-glucosidase on HA nanoparticles. The
      immobilization process was highly effective over wide ranges of pH and ionic
      strength, resulting in immobilization yields and recovered activities up to 90%.
      Investigation of the type of interaction between beta-glucosidase and HA (using
      FT-IR, zeta potential measurements, and desorption tests with different salts)
      indicated the formation of coordination bonds between Ca2+ sites of HA and COO-
      of amino acids. Even after 10 cycles of reuse, the immobilized beta-glucosidase
      retained about 70% of its initial activity, demonstrating the operational
      stability of the immobilized enzyme. The results showed that beta-glucosidase
      could be efficiently immobilized on HA nanoparticles by means of a very simple
      adsorption protocol, offering a promising strategy for performing repeated
      enzymatic hydrolysis reactions.

PMID- 30098359
TI  - Conjugation of Agrobacterium radiobacter epoxide hydrolase with ficoll:
      Catalytic, kinetic and thermodynamic analysis.
AB  - Epoxide hydrolase-mediated biocatalysis has a great prospective in the
      biosynthesis of optically pure epoxides. The present work targets toward the
      thermo-stabilization of epoxide hydrolase by covalent conjugation with
      polysaccharide. An epoxide hydrolase from Agrobacterium radiobacter (ArEH) was
      modified by covalent coupling to seven oxidized polysaccharides with different
      chemical structures and characteristics. Among all conjugates, ArEH with ficoll
      exhibited both the highest specific activity (494 U/mg) and half-life at 60 
      degrees C (t1/2 = 183 min). The conjugated enzyme also displayed wider optimum pH
      and temperature ranges, higher catalytic number (kcat), and catalytic efficiency
      (kcat/Km) as compared to its native counterpart. The conjugation significantly
      decreased the enthalpy of activation (DeltaH*), free energy of transition state
      binding (DeltaG*E-T), and free energy of activation (DeltaG*) for epichlorohydrin
      hydrolysis. Moreover, the conjugated ArEH showed enhanced thermal stability as
      evidenced by its longer half-life (t1/2), lower thermal deactivation constant
      (kd), and higher D values at 50-70  degrees C. Furthermore, the enzymatic
      activity of conjugated ArEH elevated significantly by Ca2+ and it showed
      increased tolerance against Co2+, Fe3+ and EDTA inhibitors. Finally, fluorescence
      and circular dichroism spectroscopic analysis were performed to confirm the
      noticeable conformational changes in ArEH structure after conjugation with
      ficoll, which could be responsible for the observed catalytic and stability
      enhancement.

PMID- 30098360
TI  - Structural alteration of low pH, low temperature induced protonated form of DNA
      to the canonical form by the benzophenanthridine alkaloid nitidine: Spectroscopic
      exploration.
AB  - Polymorphism of DNA plays a very important part of research relating to the drug
      DNA interactions. Here main focus of our investigation is to monitor the
      interaction of the benzophenanthridine plant alkaloid, nitidine (NIT) with two
      different forms of DNA i.e. B-DNA and protonated form of DNA maintaining proper
      temperatures and buffer conditions. Binding interaction of NIT was ascertained
      from the UV-Visible spectroscopic and spectrofluorimetric titration experiments.
      Binding constants of the interactions of NIT with different polymorphic forms
      were calculated from UV-absorption study. The binding constants were 3.8 * 105 M
      1 and 1.3 * 105 M-1 for B-DNA and protonated DNA respectively. Red shift in the
      absorption maxima of NIT on binding with DNA, comparatively greater relative
      quenching of fluorescence intensity of free NIT than bound NIT, perturbation in
      the CD spectrum of DNA in presence of NIT confirmed the mode of binding as
      intercalation. Moreover, spectropolarimetric experiment confirms that left handed
      protonated form of DNA gets partially converted to the canonical B form of DNA
      while binds with NIT. Besides the CD experiment, thermal melting experiment also
      showed that on binding with NIT stabilization of protonated DNA was increased to
      an appreciable extent.

PMID- 30098361
TI  - Identification of chemically diverse GABAA agonists as potential anti-epileptic
      agents using structure-guided virtual screening, ADMET, quantum mechanics and
      clinical validation through off-target analysis.
AB  - Development of resistance against existing anti-epileptic drugs has alarmed the
      scientific innovators to find novel potential chemical starting points for the
      treatment of epilepsy and GABAA inhibition is a promising drug target strategy
      against epilepsy. The crystal structure of a subtype-selective beta3
      homopentameric ligand-gated ion channel of GABAA receptor has been used for the
      first time for screening the Asinex library for discovery of GABAA agonists as
      potential anti-epileptic agents. Co-crystallized ligand established the
      involvement of part of the beta7-beta8 loop (Glu155 and Tyr157) and beta9-beta10
      loop (Phe200 and Tyr205) residues as the crucial amino acids in effective
      binding, an essential feature, being hydrogen bond or ionic interaction with
      Glu155 residue. Top ranked hits were further subjected to binding energy
      estimation, ADMET analysis and ligand efficiency matric calculations as
      consecutive filters. About 19 compounds qualifying all parameters possessed
      interaction of one positively charged group with Glu155 with good CNS drug-like
      properties. Simulation studies were performed on the apo protein, its complex
      with co-crystallized ligand and the best hit qualifying all screening parameters.
      The best hit was also analyzed using Quantum mechanical studies, off-target
      analysis and hit modification. The off-target analysis emphasized that these
      agents did not have any other predicted side-effects.

PMID- 30098362
TI  - Drug-loaded poly(L-lactide)/lignin stereocomplex film for enhancing stability and
      sustained release of trans-resveratrol.
AB  - We report a new drug-loaded film for blending poly(L-lactide) (PLLA) with lignin
      based functional filler, which enhanced stability and sustained release of trans
      resveratrol (trans-RSV). In addition, trans-RSV loaded PLLA/lignin films showed
      good antioxidant and anticancer effects. Incorporation of the optimized amount of
      lignin-based filler to PLLA matrix was key to achieve these desired functions.
      The lignin-based filler (LG-g-PDLA) was synthesized via ring-opening
      polymerization on alklin lignin with D-lactide. Benifiting from the stereocomplex
      formation (PLLA and PDLA side chains), similar polyphenolic structures between
      lignin and trans-RSV, and UV chromophoric groups of lignin, trans-RSV loaded
      PLLA/lignin-graft-PDLA films (R/P/LGPD) have good performances on mechanical
      property, uniformity distribution of drug, and light barrier property. The
      release behaviors of trans-RSV could be controlled by variation of LG-g-PDLA
      content. This system therefore offers great potential for the delivery of poor
      water soluble and light stability drugs.

PMID- 30098363
TI  - Effect of different drying methods on the physicochemical properties and
      antioxidant activities of mulberry leaves polysaccharides.
AB  - This study aimed to optimize the suitable drying method to obtain high yield of
      polysaccharides from mulberry leaves and to determine their structural
      characterization and antioxidant activities. The effects of three different
      drying methods such as air dried, hot air dried (55  degrees C, 65  degrees C &
      75  degrees C) and freeze dried on the physicochemical and antioxidant properties
      of mulberry leaves polysaccharides were studied using gas chromatography, high
      performance gel permeation chromatography, Fourier transform infrared
      spectroscopy, scanning electron micrography and antioxidant assays. Results
      revealed that pre-treatment remarkably influenced the changes in their
      physicochemical and antioxidant properties. In comparison with the other drying
      techniques, freeze dried polysaccharides showed more rough morphologies and
      significant antioxidant property. The yield of polysaccharides from the freeze
      dried sample was about 28.88% higher than the yield of hot air dried sample. The
      MDA activity of freeze dried sample was about 95.45%. Overall, the results
      suggested that the freeze drying technique was the appropriate method to extract
      polysaccharides from mulberry leaves that offered significant biological
      properties.

PMID- 30098364
TI  - Investigation of the magnetic field effect upon interpolymeric complexes
      formation based on bovine serum albumin and poly(aspartic acid).
AB  - The study presents a novel strategy for obtaining highly ordered interpolymeric
      complexes based on a protein, bovine serum albumin and a synthetic polymer,
      poly(aspartic acid). In this approach, experimental tests were carried out in the
      presence of a magnetic field of different intensities, namely 0.11 T and 0.3 T
      produced by permanent magnets. The influence of the magnetic force on the
      complexation process and the resulted self-assembled structures were studied by
      means of FTIR spectroscopy, X-ray diffraction, DLS, SEM microscopy and in vitro
      assay. The changes in the FTIR spectra acquired after 24 h of exposure were
      connected with conformational changes in the secondary structure and increased
      interactions between polymers, particularly when a higher intensity field was
      used. Due to a large anisotropy of magnetic susceptibility characteristic to both
      proteins and polypeptides, the magnetic field generated ordered assemblies
      consisting in globular structures of nanometric dimensions. This assembly
      strategy using magnets, along with remote manipulation capability can provide a
      versatile, contact-free, and inexpensive tool to create new, complex materials
      with tailorable characteristics.

PMID- 30098366
TI  - Cyamopsis tetragonoloba type 1 metallothionein (CtMT1) gene is upregulated under
      drought stress and its protein product has an additional C-X-C motif and unique
      metal binding pattern.
AB  - Metallothioneins (MTs) are involved in cellular homeostasis of essential metal
      ions and detoxification of nonessential metal ions. We report here the
      identification of four MT genes, CtMT1, CtMT2, CtMT3 and CtMT4, encoding CtMT1,
      CtMT2, CtMT3 and CtMT4 proteins, respectively, from the industrial guar crop. The
      primary structures of last three proteins were similar to those of respective MT
      proteins of other plants but the CtMT1 protein primary structure was different
      from the other plant MT1 proteins in having an additional C-X-C motif. The four
      MT genes showed tissue specific expression patterns suggesting their specific
      roles in different tissues. High expression of CtMT1 gene was observed in roots
      and nodules whereas CtMT2 and CtMT3 genes showed high expression in leaves. The
      expression of CtMT4 gene was high in seeds. The qRT-PCR studies revealed
      upregulation in expression of CtMT1 gene under drought stress. Recombinant CtMT1
      protein was produced in E. coli Rosetta cells and purified by metal affinity
      chromatography. The purified protein showed antioxidant property and the order of
      its metal ion binding affinities was Cu2+ > Zn2+ > Fe2+ > Cd2+. This information
      about CtMT1 protein is expected to be useful in understanding its role in drought
      tolerance and other physiological processes of guar.

PMID- 30098365
TI  - Novel vaccine candidates against Mycobacterium tuberculosis.
AB  - Tuberculosis (TB) is now among the top ten causes of mortality worldwide being
      resulted in 1.7 million deaths including 0.4 million among people with HIV in
      2016. The Bacille Calmette-Guerin (BCG) is the only available TB vaccine which
      fails to provide consistent protection against pulmonary TB in adults and
      adolescents despite being efficacious at protecting infants and young children
      from the most severe, often deadly forms of TB disease. To achieve the goal of
      global TB elimination by 2050 we will need new interventions including more
      improved vaccines that are effective in adult individuals who have not been
      infected with Mycobacterium tuberculosis as well as latently infected or
      immunocompromised subjects. In recent decades, multiple new vaccine candidates
      including whole cell vaccines, adjuvanted proteins, and vectored subunit vaccines
      have entered into the clinical trials. These new TB vaccines are hoped to provide
      encouraging safety and immunogenicity under various conditions including
      prevention of TB disease in adolescents and adults, as BCG replacement/boosters,
      or as therapeutic vaccines to reduce the duration of TB therapy. In this review,
      we will discuss the status of novel TB vaccine candidates currently under
      development in preclinical or clinical phases.

PMID- 30098367
TI  - Systematic calorimetric studies of proton exchange associated with binding of
      beta-lactoglobulin with ligand.
AB  - In proteins, proton exchange is caused due to the changes in the proton affinity
      (pKa) of ionizable groups that are engaged in conformational changes induced by
      the binding of a ligand. In addition, knowledge regarding the type and number of
      such ionizable groups is very important to understand the pH-dependent changes of
      the thermodynamic parameters. Therefore, in this study, we performed a
      comprehensive analysis of proton exchange by using beta lactoglobulin (Blg), a
      representative of the lipocalin family of proteins. We used isothermal titration
      calorimetry to evaluate the proton exchange during binding with sodium dodecyl
      sulfate (SDS) at different pHs ranging from 2 to 9. SDS binds to Blg in all
      studied range of pHs and enthalpy-driven reactions are observed in acidic pH,
      whereas enthalpy-entropy driven reactions are observed in neutral and basic pHs.
      Enthalpy-entropy compensation leads to relatively small changes in the
      association constants with the maximal value at pH = 8.0. The simultaneous
      analysis of the number of exchanged protons, the binding constants, and the
      enthalpy was performed in the range pH 5.5-9. At least 4 residues that change
      their ionization pattern are needed to explain the observed pH dependence.

PMID- 30098368
TI  - Alternatives to carcinogenic preservatives in Chinese Sausage - Sorbic acid
      loaded chitosan/tripolyphosphate nanoparticles.
AB  - Preservatives in processed meat raise significant concerns associated with bowel
      cancer and diabetes, and implicate various public health issues. This introduces
      the need for safer preservatives to uphold public health standards. However,
      developing safer alternatives to these preservatives poses a significant
      challenge to food industry. A potential solution to this issue is the use of
      loaded nanoparticles as preservative agents. This study investigated
      antimicrobial and antioxidant effects of sorbic acid-loaded
      chitosan/tripolyphosphate nanoparticles (SAN) in Chinese Sausage. SAN were
      prepared through ionic gelation, followed by natural air-drying for 20 days.
      After preparation, the antimicrobial and antioxidant activities of various
      treatment groups were analyzed intermittently during storage at room temperature.
      SAN-treated samples had significantly lower levels of surviving bacteria, molds,
      and yeasts than the blank control (p < 0.05) over the entire 72 days of storage.
      Additionally the SAN-treated samples also had lower levels of surviving bacteria
      than the chitosan/tripolyphosphate samples after 31-56 days of storage (p <
      0.05). The thiobarbituric acid value and pH of the SAN-treated samples were also
      significantly lower than the blank control (p < 0.05). These results indicated
      that SAN could be a good intervention strategy to retard lipid oxidation and
      inhibit microbial growth in Chinese Sausage.

PMID- 30098369
TI  - Incidental findings on brain MRI in a cohort of diabetic patients.
AB  - OBJECTIVE: To study the frequency and management of incidental findings in
      nonenhanced brain MRI of a middle-aged population of type 2 diabetic patients.
      METHODS: We retrospectively analyzed the results of 289 brain MRI obtained from
      subjects between 40-75 years recruited from a previous study. Incidental findings
      were classified into three categories: (1) Vascular findings; (2) neoplastic
      findings; and (3) others. On the other side, we made a classification of referral
      findings. To compare our results, we reviewed the prevalence and evidence about
      management of both incidental and referral findings in other series. RESULTS: We
      found an overall prevalence of incidental findings of 10.4% (30/289). Incidental
      findings raised according to age. The most common incidental findings were: 7
      vascular (2.4%), 6 calcifications (2.1%), 6 cystic (2.1%) and 5 neoplastic (1.7%)
      lesions. A percentage of 1.7% (5/289) were referral findings which required
      further clinical work-up. CONCLUSION: Incidental findings are relatively common
      in patients with type 2 diabetes. The most frequent are vascular findings,
      accordance with previous studies. Referral findings are uncommon. Clinical
      evidence about how to best manage the majority of incidental findings is lacking.

PMID- 30098370
TI  - Ipsilateral and contralateral cerebro-cerebellar white matter connections: A
      diffusion tensor imaging study in healthy adults.
AB  - BACKGROUND AND PURPOSE: The cerebellum has a pivotal role in regulating human
      behavior; yet whether this function is mediated only through contralateral
      cerebro-cerebellar pathways is under-investigated. Thus, we examined feed
      backward and feed-forward ipsilateral and contralateral cerebro-cerebellar
      connections using a detereministic diffusion tensor imaging (DTI) algorithm, the
      robustness of which was also estimated using phantom DTI data. MATERIALS AND
      METHODS: Fifty-one healthy controls (22-60 years old; 15 males/36 females) were
      scanned in a 3T MRI scanner with a 30-direction DTI sequence. Multiple region-of
      interest (ROI) method was applied for the reconstruction of the ipsilateral and
      contralateral (based on cerebellar seed ROI) fronto-ponto-cerebellar (FPC),
      parieto-ponto-cerebellar (PPC), temporo-ponto-cerebellar (TPC), occipito-ponto
      cerebellar (OPC) and dentate-rubro-thalamo-cortical (DRTC) tract bilaterally
      using the Brainance DTI Suite. A realistic diffusion MR phantom was used to
      evaluate the fiber tracking methodology for 16 fibers containing crossing,
      kissing, splitting and bending configurations. RESULTS: Both contralateral and
      ipsilateral FPC, PPC, OPC and ipsilateral DRTC tracts were successfully
      reconstructed; the contralateral DRTC tract was not reconstructed in all
      subjects. Also, the TPC tract was not reproduced in several subjects mostly
      regarding the contralateral connection. Descriptive DTI measures (number of
      fibers, fractional anisotropy, radial and axial diffusivity) are presented for
      each tract. Regarding phantom data, Brainance DTI Suite returned a dataset of 16
      fibers that almost perfectly matched the 16 ground truth fibers. CONCLUSIONS: We
      identified ipsilateral and contralateral connections using a clinically
      applicable DTI sequence, a robust deterministic algorithm and an unbiased
      methodology, which can be applied in daily practice in different brain
      pathologies.

PMID- 30098371
TI  - Potential effects of metformin in DNA BER system based on oxidative status in
      type 2 diabetes.
AB  - Metformin is used to reduce hyperglycemia that induces energetic stress and leads
      to reduction in gluconeogenesis. Also, metformin inhibits complex I in oxidative
      phosphorylation, thereby decreasing cellular ATP levels. Activation of AMPK by
      the reduced ATP levels can induce inhibition of reactive oxygen species (ROS)
      production and activate p53-mediated DNA repair. DNA polymerase-beta and XRCC1
      function to repair DNA damages in the BER (base excision repair) system. In type
      2 diabetes patients, metformin can enhance AMPK activation therefore suppress
      oxidative stress. The changes on oxidative stress may alter p53's function and
      effect many cellular pathways such as; DNA repair. In our project we aim to
      understand the effects of metformin on p53 and DNA-BER system based on the
      oxidative status in type 2 diabetes patients. Oxidative and antioxidative
      capacity, catalase, SOD, GPx activities and, DNA pol beta, XRCC1 and p53 levels
      were measured in metformin using or non-using type 2 diabetes patients and
      controls. Metformin enhanced SOD and GPx activities in type 2 diabetes patients
      but the reflection of this increase to the total antioxidant capacity was not
      significant. Although the increase in DNA pol beta was not significant, XRCC1 and
      p53 levels were significantly upregulated with metformin treatment in type 2
      diabetes patients. Our study reinforces the potential benefit of metformin in
      antioxidative capacity to protect cells from diabetic oxidative stress and in
      regulation of DNA BER system.

PMID- 30098372
TI  - One science-driven approach for the regulatory implementation of alternative
      methods: A multi-sector perspective.
AB  - EU regulations call for the use of alternative methods to animal testing. During
      the last decade, an increasing number of alternative approaches have been
      formally adopted. In parallel, new 3Rs-relevant technologies and mechanistic
      approaches have increasingly contributed to hazard identification and risk
      assessment evolution. In this changing landscape, an EPAA meeting reviewed the
      challenges that different industry sectors face in the implementation of
      alternative methods following a science-driven approach. Although clear progress
      was acknowledged in animal testing reduction and refinement thanks to an
      integration of scientifically robust approaches, the following challenges were
      identified: i) further characterization of toxicity pathways; ii) development of
      assays covering current scientific gaps, iii) better characterization of links
      between in vitro readouts and outcome in the target species; iv) better
      definition of alternative method applicability domains, and v) appropriate
      implementation of the available approaches. For areas having regulatory adopted
      alternative methods (e.g., vaccine batch testing), harmonised acceptance across
      geographical regions was considered critical for broader application. Overall,
      the main constraints to the application of non-animal alternatives are the still
      existing gaps in scientific knowledge and technological limitations. The science
      driven identification of most appropriate methods is key for furthering a multi
      sectorial decrease in animal testing.

PMID- 30098374
TI  - Developmental changes in the cortical sources of spontaneous alpha throughout
      adolescence.
AB  - This study investigated age-, gender-, and puberty-related changes in two
      cortical sources of spontaneous alpha during eyes-open and eyes-closed conditions
      in a cohort of adolescents aged 9-23 years. In total, 29 preadolescents (9-12
      years, 14 females), 29 mid-adolescents (13-17 years, 14 females), and 33 late
      adolescents (18-23 years, 17 females) had their resting brain activity measured
      using electroencephalography (EEG) during eyes-open and eyes-closed conditions.
      Standardised Low Resolution Brain Electromagnetic Tomography (sLORETA) was used
      to estimate the cortical sources of spontaneous alpha. Two cortical sources were
      chosen as regions of interest (ROIs): prefrontal cortex and occipital cortex.
      Significant age-related changes in the cortical sources of alpha were found,
      particularly in prefrontal regions; prefrontal alpha power was greater during the
      eyes-open condition compared to the eyes-closed condition for late adolescents,
      but equivalent across the eyes-open and eyes-closed conditions for both pre- and
      mid-adolescents. In addition, more advanced pubertal stage predicted reduced
      alpha power in male, but not female, adolescents aged 9-17 years. This study
      provides an important initial step towards understanding developmental changes in
      the cortical sources of spontaneous alpha in the typically developing brain.
      Moreover, the results from this study underscore the need to tease out the
      effects of age, gender, and puberty when examining the cortical sources of alpha
      during the adolescent period.

PMID- 30098373
TI  - No impact of resistance-associated substitutions on the efficacy of sofosbuvir,
      velpatasvir, and voxilaprevir for 12 weeks in HCV DAA-experienced patients.
AB  - BACKGROUND & AIMS: In phase III studies, the fixed dose combination of
      sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) administered for 12 weeks led
      to a sustained virologic response at 12 weeks (SVR12) in 96% of NS5A inhibitor
      experienced patients, and an SVR12 rate of 98% in DAA-experienced patients who
      had not previously received an NS5A inhibitor. Herein, we evaluate the
      relationship between the presence of detectable resistance-associated
      substitutions (RASs) at baseline and treatment outcome, and whether RASs were
      selected for in cases of virologic failure. METHODS: NS3, NS5A, and NS5B deep
      sequencing analyses were performed at baseline for all patients and at the time
      of virologic failure. Results are reported using a 15% cut-off. RESULTS: A total
      of 82.7% of NS5A inhibitor-experienced patients (205/248) had baseline NS3 and/or
      NS5A RASs; 79% had baseline NS5A RASs. SVR12 rates were similar in patients with
      or without NS3 and/or NS5A RASs, and with or without VOX- or VEL-specific RASs.
      RASs at NS5A position Y93 were present in 37.3% of patients and 95% achieved
      SVR12. All patients with >=2 NS5A RASs achieved SVR12. Baseline NS3 and/or NS5A
      RASs were present in 46.6% (83/178) of non-NS5A inhibitor DAA-experienced
      patients, all of whom achieved SVR12. All patients with baseline NS5B nucleoside
      inhibitor RASs, including two patients with S282T, achieved SVR12. Treatment
      selected resistance was seen in one of seven patients who relapsed. CONCLUSIONS:
      Baseline RASs had no impact on virologic response in DAA-experienced patients
      following treatment with SOF/VEL/VOX for 12 weeks. Selection of viral resistance
      with virologic relapse was uncommon. LAY SUMMARY: In phase III studies, 12 weeks
      of treatment with the combination of sofosbuvir, velpatasvir and voxilaprevir
      (SOF/VEL/VOX) cured 97% of patients with hepatitis C virus who failed prior
      treatment with direct-acting antiviral drugs. Herein, we show that the presence
      of pretreatment drug resistance did not affect treatment outcome in these
      patients who had previously received direct-acting antivirals. We also showed
      that new drug resistance was rare in patients who failed treatment with
      SOF/VEL/VOX for 12 weeks. This has important implications for the selection of
      best retreatment strategies for these patients.

PMID- 30098375
TI  - All-active antitumor micelles via triggered lipid peroxidation.
AB  - Traditional antitumor nanomedicines have been suffering from the poor tumor
      targeting (ca. 1%) by the enhanced permeability and retention (EPR) effect, and
      the low drug loading (<5%). It was postulated that engineering all-active
      nanoplatform could increase the therapeutic efficacy to enable the nanocarrier
      function as both vehicle and active ingredient. To achieve this, a
      photosensitizer, Ce6 was encapsulated within polymeric micelles with unsaturated
      fatty acids as the building blocks. Upon light irradiation, the singlet oxygen
      produced by Ce6 induced lipid peroxidation, resulting in the generation of both
      active free radicals and aldehydes. These supplementary radicals could exert
      cytotoxic effect for direct killing tumor cells. The aldehyde end-products
      induced significant cell cycle arrest at G2 phase in 4T1 cells. The peroxidation
      process also facilitated the on-demand disassembly of micelles and rapid release
      of Ce6 to maximize the therapeutic effect of singlet oxygen. These all-active
      micelles showed a significantly enhanced cytotoxicity with the half maximal
      inhibitory concentration (IC50) of 0.6 +/- 0.2 MUg/mL in contrast to the control
      micelles at 3.4 +/- 0.5 MUg/mL. The improved antitumor efficacy of the all-active
      micelles was also demonstrated in the 4T1 tumor-bearing mice in vivo. The current
      work provides a facile approach to enhance the antitumor efficacy of PDT
      nanomedicine using the biocompatible fatty acids, which can be applied to various
      antitumor drugs and unsaturated lipids.

PMID- 30098376
TI  - Development and validation of a universal S-segment-based real-time RT-PCR assay
      for the detection of Simbu serogroup viruses.
AB  - Simbu serogroup viruses induce acute clinical diseases and abnormal courses of
      pregnancies in livestock. In Israel, two members of this serogroup, namely
      Akabane virus (AKAV) and Shuni virus (SHUV), were recently detected and, in
      Europe, Schmallenberg virus (SBV) poses a threat to ruminants. To address this
      emerging problem, a universal S-segment-based real-time RT-PCR assay (Uni-S) for
      the detection of Simbu serogroup viruses was established, which, additionally,
      enabled species identification of the detected viruses by subsequent sequencing.
      The newly developed probe-based PCR system enabled reliable detection of a
      comprehensive panel of Simbu viruses. Furthermore, several SBV isolates and
      German field samples were tested by the new Uni-S system in comparison to a SBV
      specific real-time RT-PCR and both assays exhibited equally high levels of
      sensitivities. Finally, co-circulation of AKAV and SHUV in Israel was confirmed
      by analyzing field samples using the Uni-S assay followed by sequence analysis of
      the positive samples. To validate the test specificity, blood and tissue samples
      from animals negative for Simbu viruses, preparations of genetically related
      viruses and additional ruminant pathogens were examined and all were found to be
      negative. In conclusion, the new assay enabled sensitive and rapid universal
      molecular detection of Simbu viruses and is expected to serve as a valuable
      method for infection diagnosis, especially in regions where several Simbu
      serogroup members circulate.

PMID- 30098377
TI  - NLRP3 deficiency ameliorates renal inflammation and fibrosis in diabetic mice.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease.
      Activation of the nucleotide binding and oligomerization domain-like receptor
      family pyrin domain-containing 3 (NLRP3) inflammasome has been reported in
      diabetic kidney, yet the potential role of NLRP3 inflammasome in DN is not well
      known. In this study, we explored the role of NLRP3 inflammasome on inflammation
      and fibrosis in diabetic kidney using NLRP3 knockout mice. Renal expression of
      NLRP3, caspase-1 p10, interleukin-18 (IL-18) and cleaved IL-1beta was increased
      in diabetic wild-type (WT) mice at 24 weeks. NLRP3 knockout (KO) improved renal
      function, attenuated glomerular hypertrophy, glomerulosclerosis, mesangial
      expansion, interstitial fibrosis, inflammation and expression of TGF-beta1 and
      connective tissue growth factor (CTGF), as well as the activation of Smad3 in
      kidneys of STZ-induced diabetic mice. In addition, NLRP3 KO inhibited expression
      of thioredoxin-interacting protein (TXNIP) and NADPH oxidase 4 (Nox4) and
      superoxide production in diabetic kidneys. The diabetes-induced increase in
      urinary level of 8-hydroxydeoxyguanosine (8-OHdG) was attenuated in NLRP3 KO
      mice. In vitro experiments, using HK-2 cells, revealed that high glucose (HG)
      mediated expression of TXNIP and Nox4 was inhibited by transfection with NLRP3
      shRNA plasmid or antioxidant tempol treatment. Silencing of the NLRP3 resulted in
      reduced generation of reactive oxygen species (ROS) in HK-2 cells under HG
      conditions. Furthermore, we also found exposure of IL-1beta to HK-2 cells induced
      ROS generation and expression of TXNIP and Nox4. Taken together, inhibition of
      NLRP3 inflammasome activation inhibits renal inflammation and fibrosis at least
      in part via suppression of oxidative stress in diabetic nephropathy.

PMID- 30098379
TI  - Phenylpropanoids and Alzheimer's disease: A potential therapeutic platform.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by
      progressive dementia, neuroinflammation and the accumulation of intracellular
      neurofibrillary tangles and extracellular plaques. The etiology of AD is unclear,
      but is generally attributed to four leading hypotheses: (i) abnormal folding and
      aggregation of amyloid-beta (Abeta)/tau proteins (ii) activation of the innate
      immune system, (iii) mitochondrial dysfunction, and (iv) oxidative stress. To
      date, therapeutic strategies have largely focused on Abeta-centric targets;
      however, the repeated failure of clinical trials and the continued lack of a
      disease-modifying therapy demand novel, multifaceted approaches. Natural products
      are common molecular platforms in drug development; in AD, compounds from the
      plant phenylpropanoid metabolic pathway have yielded promising associations.
      Herein, we review developments in the pathogenesis of AD and the metabolism of
      phenylpropanoids in plants. We further discuss the role of these metabolites as
      relevant to the four leading mechanisms of AD pathogenesis, and observe multiple
      protective effects among phenylpropanoids against AD onset and progression.

PMID- 30098378
TI  - Early behavioral and metabolomic change after mild to moderate traumatic brain
      injury in the developing brain.
AB  - Pathophysiology of developmental traumatic brain injury (TBI) is unique due to
      intrinsic differences in the developing brain. Energy metabolic studies of the
      brain during early development (P13 to P30) have indicated acute oxidative energy
      metabolic decreases below 24 h after TBI, which generally recovered by 48 h.
      However, marked neurodegeneration and altered neural functional connectivity have
      been observed at later stages into adolescence. As secondary neurodegeneration is
      most prominent during the first week after TBI in the rat model, we hypothesized
      that the subacute TBI-metabolome may contain predictive markers of
      neurodegeneration. Sham and TBI metabolomes were examined at 72 h after a mild to
      moderate intensity TBI in male Sprague-Dawley rats aged P31. Sensorimotor
      behavior was assessed at 24, 48 and 72 h after injury, followed by 72-hour
      postmortem brain removal for metabolomics using Liquid Chromatography/Mass
      Spectrometry (LC-MS) measurement. Broad TBI-induced metabolomic shifts occurred
      with relatively higher intensity in the injury-lateralized (ipsilateral)
      hemisphere. Intensity of metabolomic perturbation correlated with the extent of
      sensorimotor behavioral deficit. N-acetyl-aspartate (NAA) levels at 72 h after
      TBI, predicted the extent of neurodegeneration assessed histochemically 7-days
      post TBI. Results from the multivariate untargeted approach clearly distinguished
      metabolomic shifts induced by TBI. Several pathways including amino acid, fatty
      acid and energy metabolism continued to be affected at 72 h after TBI, whose
      collective effects may determine the overall pathological response after TBI in
      early development including neurodegeneration.

PMID- 30098380
TI  - Substantial Reduction in Driveline Infection Rates With the Modification of
      Driveline Dressing Protocol.
AB  - BACKGROUND: Driveline infection (DLI) is a cause of morbidity and mortality in
      patients with continuous-flow left ventricular assist devices (CF-LVADs). We
      hypothesized that an alternate dressing protocol would decrease the rate of DLIs.
      METHODS AND RESULTS: A retrospective review of CF-LVAD implants at a single
      institution from January 2010 to October 2015 was conducted. Patients were
      divided into implants before (group 1) and after (group 2) the introduction of
      the new protocol on September 1, 2012. Patients were followed until death,
      transplantation, change in dressing type, or 2 years. 153 patients were included:
      61 in group 1 and 92 in group 2. Group 1 had fewer HVADs than group 2 (27.9% vs
      71.7%; P < .001) and more destination therapy, although the latter was not
      statistically significant (50.8% vs 34.8%; P = .118). At 24 months, the freedom
      from DLI was 53% in group 1 and 89% in group 2 (P = .01). Group 1 had a
      significantly greater risk of DLI than group 2 (incident rate ratio 3.18, 95%
      confidence interval 1.23-8.18; P = .016). CONCLUSIONS: Dramatic improvement in
      freedom from DLI at 2 years was achieved with a new driveline dressing protocol.
      This demonstrates that DLI rates can be improved with alternate percutaneous site
      care techniques in CF-LVAD patients.

PMID- 30098381
TI  - Calculated Estimates of Plasma Volume in Patients With Chronic Heart Failure
      Comparison With Measured Volumes.
AB  - BACKGROUND: Calculated estimates of plasma volume (PV) have been developed with
      the use of hemoglobin/hematocrit-body weight-based methods. The accuracy of such
      formula-derived values has not been thoroughly evaluated. The objective of this
      analysis was to compare the calculated estimate and a quantitative measure of PV
      in patients with chronic heart failure (HF). METHODS AND RESULTS: PV was measured
      with the use of a standardized computer-based indicator-dilution-labeled albumin
      technique in 110 patients with clinically stable chronic HF and correlated with
      paired Kaplan-Hakim (K-H) and Strauss formula estimates of PV. The K-H formula
      underestimated (3.4 +/- 0.7 L) and the Strauss formula overestimated (5.3 +/- 1.5
      L) PV relative to the measured volume (4.3 +/- 1.1 L). Calculated PV was only
      moderately correlated with measured PV by the K-H formula (r = 0.64; P < .001)
      and weakly by the Strauss formula (r = 0.285; P = .003). Strauss formula
      estimates of change (%) in PV were also poorly correlated with paired measured
      changes in PV (r = 0.162; P = .999; n = 40). CONCLUSIONS: Calculated estimates of
      PV demonstrate limited association with measured volumes. These findings indicate
      that although formula-based estimates of PV have been shown to have prognostic
      value, they are limited in their reliability for volume management in patients
      with chronic HF.

PMID- 30098382
TI  - Barriers and enablers to meticillin-resistant Staphylococcus aureus admission
      screening in hospitals: a mixed-methods study.
AB  - BACKGROUND: To reduce the risk of transmission of meticillin-resistant
      Staphylococcus aureus (MRSA), international guidelines recommend admission
      screening to identify hospital patients at risk of colonization. However, routine
      monitoring indicates that optimum screening compliance levels are not always
      achieved. In order to enhance compliance, we must better understand those factors
      which influence staff screening behaviours. AIM: To identify factors which
      influence staff compliance with hospital MRSA screening policies. METHODS: A
      sequential two-stage mixed-methods design applied constructs from normalization
      process theory and the theoretical domains framework to guide data collection and
      analysis. Initial qualitative findings informed subsequent development of a
      national cross-sectional survey of nursing staff (N = 450). Multiple regression
      modelling identified which barriers and enablers best predict staff compliance.
      FINDINGS: Three factors were significant in predicting optimum (>90%) compliance
      with MRSA screening: having MRSA screening routinized within the admission
      process; category of clinical area; feedback of MRSA screening compliance within
      the clinical area. Integration of data-sets indicated that organizational systems
      which 'make doing the right thing easy' influence compliance, as does local ward
      culture. Embedded values and beliefs regarding the relative (de)prioritization of
      MRSA screening are important. CONCLUSION: To our knowledge, this is the first
      study to provide original evidence of barriers and enablers to MRSA screening,
      applying both sociological and psychological theory. As antimicrobial resistance
      is a global health concern, these findings have international relevance for
      screening programmes. Future policy recommendations or behaviour change
      interventions, based on the insights presented here, could have significant
      impact upon improving screening compliance.

PMID- 30098384
TI  - Stroke in CNS white matter: Models and mechanisms.
AB  - White matter stroke (WMS) is a debilitating disorder, which is characterized by
      the formation of ischemic lesions along subcortical white matter tracts of the
      central nervous system. Initial infarction during the early stages of the disease
      is often asymptomatic and is thus considered a form of silent stroke. However,
      over time lesions accumulate, resulting in severe cognitive and motor decline of
      which there are no known therapies. Functional imaging and post mortem analysis
      of patients demonstrates a loss of oligodendrocytes and the subsequent damage of
      myelin as a primary hallmark of WMS lesions. Though the adult mammalian brain
      maintains the capacity to regenerate adult oligodendrocytes, this process is
      blocked in the infarcted white matter thereby preventing remyelination. Recent
      evidence suggests that activation of neural circuits via motor training or direct
      stimulation drives oligodendrogenesis and de novo myelin synthesis, opening a
      potential avenue for therapy in WMS.

PMID- 30098383
TI  - In schizophrenia serum level of neurotrophin-3 (NT-3) is increased only if
      depressive symptoms are present.
AB  - AIM: Neurotrophin-3 (NT-3) is a neurotrophic factor responsible for promoting
      development, survival and function of neurons. NT-3 may be involved in the
      etiopathology of schizophrenia and mood disorders. However it must be cleared up
      if changes of NT-3 level are associated with schizophrenia itself or are
      secondary to certain symptoms (e.g. negative or depressive). The aim of this
      study was to examine whether the presence of negative or depressive symptoms
      affects peripheral NT-3 concentration in patients with schizophrenia. METHODS:
      Data for 69 Caucasian adult hospitalized patients with chronic paranoid
      schizophrenia was compared with 27 healthy subjects. Level of NT-3 was measured
      in blood serum using enzyme-linked immunosorbent assay. Clinical symptoms were
      assessed using the Positive and Negative Syndrome Scale (PANSS) and Calgary
      Depression Scale for Schizophrenia (CDSS). RESULTS: Patients were stratified into
      three sub-groups: non-depressed with no dominating negative symptoms (DEP-/NEG-),
      non-depressed with dominating negative symptoms (DEP-/NEG+) and depressed with
      dominating negative symptoms (DEP+/NEG+). Mean NT-3 concentration was higher in
      the DEP+/NEG + sub-group (202.61 +/- 258.76 pg/mL) compared with the DEP-/NEG+
      (83.79 +/- 215.75 pg/mL), DEP-/NEG- (83.79 +/- 215.75 pg/mL) and control (36.47
      +/- 73.84 pg/mL) sub-groups (p = 0.016). CONCLUSION: We found that in
      schizophrenia serum level of neurotrophin-3 (NT-3) is increased only if
      depressive symptoms are present. There was no difference in NT-3 level between
      schizophrenia patients and controls.

PMID- 30098385
TI  - Early diagnosis of radio-insensitive human nasopharyngeal carcinoma xenograft
      models by diffusion kurtosis imaging.
AB  - OBJECTIVE: To investigate the feasibility of DKI in early detection of radio
      insensitive nasopharyngeal carcinoma (NPC) xenografts in nude mice. MATERIALS AND
      METHODS: Seventy-two nude mice were implanted with CNE-1 (low radio-sensitive)
      and CNE-2 (high radio-sensitive) NPC cell lines, and their respective xenografts
      were obtained. Then, the NPC-bearing nude mice were exposed to different doses of
      fraction irradiation, which are divided into non-irradiated group (G0), 10Gy
      group (G1), 20Gy group (G2), 30Gy group (G3), 3rd (G4) and 5th (G5) days after
      the entire dose (30y) of irradiation. Subsequently, DKI was performed on each
      group. Tumor volumes, shrink rates, D and K parameters were measured by two
      experienced radiologists. Student's t-test and receiver operating characteristic
      (ROC) curve analysis were conducted in this study. RESULTS: The differences of
      volume shrinkage rate between CNE-1 and -2 were observed in G2 (P = 0.032), with
      the shrink rates of 5.954% and 27.716%, respectively. The D values were reduced
      at G1 (DG1, P = 0.001) and then increased gradually after irradiation. The K
      values were increased at G1 (KG1, P = 0.001) and then declined sharply in CNE-2
      (P < 0.01), but not in CNE-1 xenografts (P > 0.05). The respective AUC values for
      DG1 and KG1 were 0.875 and 0.917, with 66.7% and 83.3% sensitivity and 100%
      specificity, at the cutoff values of 1.27 * 10-3 mm2/s for parameter D and 0.88
      for parameter K. CONCLUSION: DKI can be used for early detection of radio
      insensitive NPC xenografts prior to morphological change, where DG1 and KG1 may
      be the most valuable indicators.

PMID- 30098386
TI  - KIDS SAVE LIVES-Three years of implementation in Europe.

PMID- 30098387
TI  - DSP-4 induced depletion of brain noradrenaline and increased 6-hertz psychomotor
      seizure susceptibility in mice is prevented by sodium valproate.
AB  - The central neurotransmitters assume a noteworthy part in the pathophysiology of
      epilepsy, noradrenaline is one of them. However, its role in 6 Hz induced
      psychomotor seizures is not known. The present study was, therefore, designed to
      investigate the role of noradrenaline (NA) in 6 Hz-induced psychomotor seizures
      in Swiss albino mice using N-2-Chloroethyl-N-ethyl-2-bromobenzylamine
      hydrochloride (DSP-4), a well-known depletor of NA. The vehicle and DSP-4 treated
      mice were given 6 Hz stimulation. A sham treatment was utilized as a comparator
      and sodium valproate (SVP) was utilized as a reference anti-epileptic medication.
      Behavioral changes instigated by 6 Hz stimulation were described as the increased
      duration of Straub's tail, stun position, twitching of vibrissae, forelimb clonus
      and increased rearing and grooming. DSP-4 administration further amplified the
      seizures and behavioral changes while pretreatment with SVP reduced the same in
      mice. Further, SVP pre-treatment also attenuated the ultra-structural changes
      observed in cortex and hippocampus of mice treated with DSP-4 and 6 Hz. Finally,
      the neurochemical estimation of NA in cortex and hippocampus confirmed the
      depletion of NA following DSP-4 and 6 Hz seizures. SVP pretreatment (but not post
      treatment) protected the mice from 6 Hz seizures and attenuated the DSP-4 induced
      alterations of nor-adrenaline content in the mouse brain. The study indicates low
      brain NA content to enhance pharmacoresistant seizures in mice and demonstrates
      that SVP mediated protection against 6 Hz results possibly via modulation of NA
      content.

PMID- 30098388
TI  - Astrocytic rather than neuronal P2X7 receptors modulate the function of the tri
      synaptic network in the rodent hippocampus.
AB  - Whole-cell patch clamp recordings demonstrated that in the dentate gyrus (DG) as
      well as in the CA3 area of mouse hippocampal slices the prototypic P2X7 receptor
      (R) agonist dibenzoyl-ATP (Bz-ATP) induced inward current responses both in
      neurons and astrocytes. Whereas the selective P2X7R antagonist A438079 strongly
      inhibited both neuronal and astrocytic currents, a combination of ionotropic
      glutamate receptor (CNQX, AP-5) and GABAA-R (gabazine) antagonists depressed the
      Bz-ATP-induced current responses in the DG (granule cells) and CA3 neurons only.
      It was concluded that Bz-ATP activated astrocytic P2X7Rs and thereby released
      glutamate and GABA to stimulate nearby neurons. The residual A438079-resistant
      current response of astrocytes was suggested to be due to the stimulation of
      P2XRs of the non-P2X7-type. Further, we searched for presynaptic P2X7Rs at the
      axon terminals of DG and CA3 pyramidal neurons innervating CA3 and CA1 cells,
      respectively. Bz-ATP potentiated the frequency of spontaneous postsynaptic
      currents (sPSCs) in CA1 but not CA3 pyramidal cells. However, the Bz-ATP effect
      in CA1 cells was inhibited by gabazine or the astrocytic toxin fluorocitrate
      suggesting stimulation of P2X7Rs at stratum radiatum astrocytes located near to
      interneurons and synapsing onto CA1 neurons. Our data suggest that functional
      P2X7Rs are missing at neurons in the tri-synaptic network of the rodent
      hippocampus, but are present at nearby astrocytes indirectly regulating network
      activity.

PMID- 30098389
TI  - 8-(3-phenylpropyl)-1,3,7-triethylxanthine is a synthetic caffeine substitute with
      stronger metabolic modulator activity.
AB  - Caffeine is one of the most worldwide consumed methylxanthines. It is well-known
      for its thermogenic and cell metabolism modulating effects. Based on
      methylxanthines' chemical structure, 8-(3-phenylpropyl)-1,3,7-triethylxanthine
      (PTX) is a novel adenosine antagonist with higher receptor affinity than
      caffeine. Therefore, we hypothesized that PTX metabolic effects could be stronger
      than those of caffeine. For that purpose, murine 3T3-L1 cells were cultured in
      the presence of increasing doses of PTX or caffeine (0.1, 1, 10 and 100 MUM) for
      24 h. Cytotoxicity was evaluated by reduction of tetrazolium salt (MTT) and
      lactate dehydrogenase (LDH) release. Cell metabolites released to the culture
      medium were identified and quantified by proton nuclear magnetic resonance (1H
      NMR). Cellular oxidative profile was also evaluated. Our results showed that PTX
      displayed no signs of cytotoxicity at all studied concentrations. When compared
      with caffeine, PTX increased glucose, pyruvate, and glutamine consumption, as
      well as lactate, alanine, and acetate production. Additionally, PTX decreased
      protein oxidation, thus protecting against oxidative stress-induced damage. These
      results illustrate that PTX is a stronger and less cytotoxic caffeine substitute
      with potential applications as metabolic modulator and a good candidate for novel
      drug design.

PMID- 30098390
TI  - Design and validation of a simple device for insufflation of dry powders in a
      mice model.
AB  - Delivery of inhalational dry powders (DPs) to the lung of mice is pivotal for pre
      clinical pharmacokinetic and pharmacodynamic investigations. Although several
      devices have been reported, their application is always limited by many factors,
      including complicated design, high price, commercially discontinued status, as
      well as requirement of special skills. Here, we have introduced a simple device
      for non-invasive and precise delivery of DPs in mice. We set up the self-made
      device using a 20 G cannula tube and a 1 mL syringe. Subsequently, it was
      validated in terms for proper installation, delivery of dry powder and safety.
      Taken together, we believe that this device will be helpful in pre-clinical
      studies, especially in laboratory experiments, for respiratory drug delivery in
      small animal models.

PMID- 30098391
TI  - An examination of protein binding and protein-facilitated uptake relating to in
      vitro-in vivo extrapolation.
AB  - As explained by the free drug theory, the unbound fraction of drug has long been
      thought to drive the efficacy of a molecule. Thus, the fraction unbound term, or
      fu, appears in equations for fundamental pharmacokinetic parameters such as
      clearance, and is used when attempting in vitro to in vivo extrapolation (IVIVE).
      In recent years though, it has been noted that IVIVE does not always yield
      accurate predictions, and that some highly protein bound ligands have more
      efficient uptake than can be explained by their unbound fractions. This review
      explores the evolution of fu terms included when implementing IVIVE, the concept
      of protein-facilitated uptake, and the mechanisms that have been proposed to
      account for facilitated uptake.

PMID- 30098392
TI  - Rate of small-molecular drug transport across the blood-brain barrier in a
      pericyte-deficient state.
AB  - Close interactions between pericytes and brain endothelial cells are essential
      for keeping the blood-brain barrier (BBB) functional and to restrict the
      transport of various xenobiotics from blood circulation to the brain parenchyma.
      Profound understanding of pericyte roles at the BBB and underlying mechanisms for
      the regulation of BBB transport are important as a potential strategy to improve
      drug delivery in treatment of CNS disorders. The aim of the present study was to
      investigate pericyte role in the rate of small-molecular drug transport across
      the BBB, by examining three model compounds in a pericyte-deficient state.
      Diazepam, oxycodone and paliperidone were selected for this purpose based on
      utilization of different transport mechanisms at the BBB. The rate of brain
      uptake was assessed by implementing the trans-cardiac in situ brain perfusion
      technique. Radiolabeled 14C-sucrose was used as a vascular marker. Pericyte
      deficient mice (Pdgfbret/ret) exhibited significantly larger brain vascular
      volumes (Vvasc) 1.72 +/- 0.13 mL/100 g brain, compared to littermate controls
      with normal pericyte coverage (Pdgfbret/+) 1.15 +/- 0.13 mL/100 g brain (p <
      0001). However, the unidirectional transfer coefficient Kin, which describes the
      rate of brain uptake, was not different between Pdgfbret/ret and Pdgfbret/+ mice
      for all three tested compounds. Taken together the present results indicate no
      pericyte influence in the rate of small-molecular drug transport at the BBB,
      despite the larger brain vascular volumes that were observed in a pericyte
      deficient state.

PMID- 30098393
TI  - Rates and Risk Factors for Post-Traumatic Stress Disorder Symptomatology among
      Adult Hematopoietic Cell Transplant Recipients and Their Informal Caregivers.
AB  - Hematopoietic cell transplant (HCT) can cause significant distress in patients
      and their informal caregivers. Despite advances in reduced-intensity conditioning
      and supportive care, few recent studies have reported rates of clinically
      significant post-traumatic stress disorder (PTSD) symptomatology. Goals of the
      current study were to examine rates of PTSD and distress in patients and
      caregivers and to identify sociodemographic and clinical risk factors for PTSD.
      As part of an annual survivorship survey, 2157 HCT recipients and their
      caregivers were mailed self-report measures of PTSD and distress. Patients also
      completed self-report measures of sociodemographic information (eg, age, sex,
      employment status). Clinical variables (eg, time since transplant, transplant
      type) were captured in the transplant database. A total of 691 recipients (56%
      age 60 or above at the time of survey, 47% women, median 10.1 years post-HCT) and
      333 caregivers provided PTSD data and were included in the current analyses. More
      caregivers reported PTSD (6.6%) than patients (3.3%; P = .02). Patients or
      caregivers who had PTSD reported significantly higher distress related to
      uncertainty, family strain, medical demands, finances, identity, and health
      burden (P < .0001) compared with those without PTSD. Patient but not caregiver
      PTSD was associated with more recent transplant (P = .01 and P = .16,
      respectively). Rates of PTSD are relatively low in long-term survivors of HCT and
      their caregivers. Nevertheless, results are consistent with other studies of
      cancer caregiving suggesting that caregivers often experience greater distress
      than patients. Timely referral to psychosocial services should be offered to both
      HCT recipients and caregivers reporting symptoms of PTSD.

PMID- 30098394
TI  - Prospective Evaluation of a Practical Guideline for Managing Positive Sterility
      Test Results in Cell Therapy Products.
AB  - Product safety assurance is crucial for the clinical use of manufactured cellular
      therapies. A rational approach for delivering products that fail release criteria
      (because of potentially false-positive sterility results) is important to avoid
      unwarranted wastage of highly personalized and costly therapies in critically ill
      patients where benefits may outweigh risk. Accurate and timely interpretation of
      microbial sterility assays represents a major challenge in cell therapies. We
      developed a systematic protocol for the assessment of positive microbial
      sterility test results using retrospective data from 2007 to 2016. This protocol
      was validated and applied prospectively between October 2016 and September 2017
      to 13 products from which positive sterility results had been reported. Viable
      and nonviable environmental monitoring (EM) data were collected concurrently as
      part of a facility control assessment. Three of 13 (23%) positive sterility
      results were attributable to bone marrow collections that had been contaminated
      with skin flora during harvest; all were infused without pertinent infectious
      sequelae. Of the remaining 10, 1 was deemed a true positive and was discarded
      before infusion, whereas 9 were classified as false positives attributed to
      laboratory sampling and/or culturing processes. Three products deemed false
      positive were infused and 6 were withheld because of patient issues unrelated to
      microbial sterility results. No postinfusion-associated infectious complications
      were documented. Almost half of the positive EM findings were skin flora. Paired
      detection of an organism in both product and associated EM was identified in 1
      case. Application of our validated protocol to positive product sterility test
      results allowed for systematic data compilation for regulatory evaluation and
      provided comprehensive information to clinical investigators to ensure timely and
      strategic management for product recipients.

PMID- 30098395
TI  - Neurochemical difference between somato- and viscero-projecting sensory neurons
      in the pig.
AB  - The chemical coding of porcine somato (skin)- and viscero (urinary bladder)
      projecting sensory neurons have been studied and compared using
      immunohistochemistry. Cell bodies of skin and bladder afferents were identified
      following Fast Blue injections into the skin of the hind leg as well as into wall
      of the urinary bladder, respectively. Immunohistochemistry revealed that small
      and medium-sized neurons projecting to both skin and bladder contained all of the
      studied substances i.e. substance P (SP), calcitonin gene-related pepide (CGRP),
      transient receptor potential vanilloid (TRPV1), lectin from Bandeiraea
      simplicifolia - Griffonia simplicifolia isolectin B4 (IB4) and galanin (GAL).
      Moreover, small-sized sensory neurons projecting to the bladder and skin of hind
      leg showed predominantly immunoreactivity to SP and TRPV1 and CGRP, as well as to
      CGRP and TRPV1 and IB4. It is worth stressing that the subset of sensory neurons
      innervating the skin exhibited these substances more often than bladder
      projecting neurons. In addition, medium-sized skin-projecting neurons contained
      SP/GAL; SP/CGRP and CGRP/IB4 much more often than their bladder counterparts. On
      the other hand, small-sized perikarya that innervate the skin were less
      frequently expressed TRPV1, CGRP and GAL than the bladder-projecting neurons. In
      conclusion, the present report describes, for the first time, significant
      differences in the chemical coding between somato- and viscero-projecting sensory
      neurons in dorsal root ganglia. Moreover, these results provide morphological
      basis for further functional studies, which may explain the exact roles played by
      various subpopulations of somato- and viscero-projecting sensory neurons.

PMID- 30098396
TI  - Fluorescent genetic barcoding for cellular multiplex analyses.
AB  - Hematopoiesis depends on the controlled differentiation of hematopoietic stem
      cells to mature cells with defined functions. Although each cell population
      within the hematopoietic hierarchy can be described by phenotypic markers,
      isolation of marker pure populations does not necessarily result in cells with
      homogeneous functionality. However, techniques that enable the efficient
      characterization of cell behavior with high resolution are limited. Although
      single-cell transplantation assays demand high mouse numbers and workload,
      sequencing-based fate tracking techniques require the destruction of the host
      cell, substantial financial resources, and bioinformatics expertise and suffer
      from a delay between sample acquisition and data interpretation. To make analyses
      more efficient, several laboratories recently developed flow cytometry-driven,
      fluorescence-based multiplexing approaches that enable parallel analysis of
      longitudinal behavior from multiple clonally derived cells or polyclonal
      populations. Although these fluorescent genetic barcoding systems are still in
      their infancy, their power lies in the use of retroviral vectors for gene marking
      of multiple populations with unique fluorescent color codes. Tracing of color
      coded cells by flow cytometry guarantees the accessibility of information on
      population behavior in real time and at low cost, supports the prospective
      isolation of cells for downstream analyses, and can be applied to cell line
      models as well as to human- and animal-derived primary cells. Here, we discuss
      recent progress in the emerging field of fluorescent genetic barcoding for
      longitudinal multiplex cell tracking in biomedical research and how this
      technique will help to uncover mechanisms regulating cell behavior with clonal
      resolution in a reduced number of experimental samples.

PMID- 30098397
TI  - Molecular pathophysiology and genetic mutations in congenital sideroblastic
      anemia.
AB  - Sideroblastic anemia is a heterogeneous congenital and acquired disorder
      characterized by anemia and the presence of ring sideroblasts in the bone marrow.
      Congenital sideroblastic anemia (CSA) is a rare disease caused by mutations in
      genes involved in the heme biosynthesis, iron-sulfur [Fe-S] cluster biosynthesis,
      and mitochondrial protein synthesis. The most prevalent form of CSA is X-linked
      sideroblastic anemia, caused by mutations in the erythroid-specific delta
      aminolevulinate synthase (ALAS2), which is the first enzyme of the heme
      biosynthesis pathway in erythroid cells. To date, a remarkable number of
      genetically undefined CSA cases remain, but a recent application of the next
      generation sequencing technology has recognized novel causative genes for CSA.
      However, in most instances, the detailed molecular mechanisms of how defects of
      each gene result in the abnormal mitochondrial iron accumulation remain unclear.
      This review aims to cover the current understanding of the molecular
      pathophysiology of CSA.

PMID- 30098398
TI  - Toll-like receptor (TLR)4 signalling induces myeloid differentiation primary
      response gene (MYD) 88 independent pathway in avian species leading to type I
      interferon production and antiviral response.
AB  - Engagement of toll-like receptor (TLR)4 ligand, lipopolysaccharide (LPS) with
      TLR4 in mammals activates two downstream intracellular signaling routes; the
      myeloid differentiation primary response gene (MyD)88 dependent and independent
      pathways. However, existence of the later pathway leading to production of type I
      interferons (IFNs) in avian species has been debated due to conflicting
      observations. The objective of our study was to investigate whether LPS induces
      type I IFN production in chicken macrophages leading to antiviral response
      attributable to type I IFN. We found that LPS elicits type I IFN response
      dominated by IFN-beta production. We also found that reduction in infectious
      laryngotracheitis virus (ILTV) replication by LPS-mediated antiviral response is
      attributable to type I IFNs in addition to nitric oxide (NO). Our findings imply
      that LPS elicits both MyD88 dependent and independent pathways in chicken
      macrophages consequently eliciting anti-ILTV response attributable to production
      of both type I IFNs and NO.

PMID- 30098399
TI  - Exosomes derived from hypoxic epithelial ovarian cancer cells deliver microRNAs
      to macrophages and elicit a tumor-promoted phenotype.
AB  - Recently, cancer has been considered to be a complex system that includes the
      tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most
      common immune-related stromal cells in the TME, and communication between cancer
      cells and TAMs is crucial for the progression of epithelial ovarian cancer (EOC).
      In this study, we revealed that exosomes derived from EOC cells remodel
      macrophages to a tumor-promoted phenotype, namely TAMs. In addition, hypoxic
      microenvironments have been postulated to facilitate this process in the TME, and
      hypoxia-inducible factors (HIFs) play an important role in this process. We found
      that TAMs educated by hypoxic exosomes derived from EOC cells promote tumor
      proliferation and migration in a feedback loop. Based on microarray analysis of
      normoxic and hypoxic exosomes, we discovered that a panel of miRNAs was enriched
      in hypoxic exosomes. And these three highly expressed miRNAs were induced by
      hypoxia via HIFs. In this study, we revealed that under hypoxic conditions, EOC
      cell-derived exosomes deliver miRNAs to induce M2 macrophage polarization, which
      promotes EOC cell proliferation and migration. This study suggests that these
      exosomes and associated miRNAs might serve as targets for novel treatments or
      diagnostic biomarkers for EOC.

PMID- 30098400
TI  - Tannins from Syzygium guineense suppress Wnt signaling and proliferation of Wnt
      dependent tumors through a direct effect on secreted Wnts.
AB  - Triple-negative breast cancer (TNBC) and colon cancer (CC) are two stigmatic
      examples of poorly treatable tumors, whose progression critically depends upon
      hyperactivation of the Wnt signaling. Development of specific anti-Wnt inhibitors
      is required to develop drugs against these and other Wnt-dependent cancers.
      Natural products, especially plants, have been used for the treatment of various
      diseases from ancient times. We examined extracts from several indigenous
      Cameroonian herbs and tested their effects on proliferation and Wnt signaling in
      TNBC and CC cells. Extracts from "fruit rouge", Syzygium guineense Wall.
      (Myrtaceae), demonstrated a strong activity against these cancer cells, as well
      as CC organoids. We found TNBC cells to significantly upregulate expression of
      Wnt3a, and the effects of S. guineense extracts on TNBC cell proliferation
      correlated with inhibition of the Wnt3a-induced beta-catenin stabilization and
      transcriptional response. HPLC analysis revealed that the active components
      belong to tannins. We found a direct destabilizing effect of S. guineense extract
      on Wnt3a and other Wnt proteins, identifying a novel mechanism of action of
      tannins on the Wnt signaling pathway and cancer cell proliferation. Being edible,
      this African plant may have an important cancer-preventive nutritional value.

PMID- 30098401
TI  - cAMP/PKA-induced filamin A (FLNA) phosphorylation inhibits SST2 signal
      transduction in GH-secreting pituitary tumor cells.
AB  - An efficient intracellular response to somatostatin analogs (SSA) in pituitary
      tumors requires filamin A (FLNA). Since cAMP pathway plays an important role in
      GH-secreting pituitary tumors pathogenesis and FLNA is phosphorylated by PKA on
      S2152, aim of this study was to investigate in tumoral somatotrophs the impact of
      cAMP pathway activation and SSA stimulation on FLNA phosphorylation and the
      consequences on SST2 function. We found a PKA-mediated increase (2-fold) and SST2
      agonist-induced decrease (-50%) of FLNA phosphorylation in GH3, GH4C1 and primary
      somatotroph tumor cells. This modification regulates FLNA function. Indeed,
      phosphomimetic S2152D FLNA mutant, but not phosphodeficient S2152A, abolished the
      known SSA antitumoral effects, namely: 1) inhibition of cell proliferation,
      reduction of cyclin D3 and increase of p27; 2) increase of cell apoptosis; 3)
      inhibition of cell migration via RhoA activation and cofilin phosphorylation.
      Coimmunoprecipitation and immunofluorescence assays showed that S2152A FLNA was
      recruited to activated SST2, whereas S2152D FLNA constitutively bound SST2 on the
      plasma membrane, but prevented Galphai proteins recruitment to SST2. In
      conclusion, we demonstrated that FLNA phosphorylation, promoted by cAMP pathway
      activation and inhibited by SSA, prevented SST2 signaling in GH-secreting tumoral
      pituitary cells.

PMID- 30098402
TI  - B-cell and T-cell epitope identification with stability analysis of AI-2 import
      ATP-binding cassette LsrA from S. typhiIn silico approach.
AB  - Typhoid fever is a severe illness in humans, caused by Salmonella typhi, a Gram
      negative bacterium. Membrane proteins of S. typhi have strong potential for its
      use in development of subunit vaccine against typhoid. In current study, peptide
      based subunit vaccine constructed from AI-2 import ATP-binding cassette
      transporter protein (LsrA) against S. typhi. B-cell and T-cell epitopes were
      identified at fold level with validated 3-D theoretical modelled structure. T
      cell epitope from LsrA (LELPGSRPQ) has binds to maximum number (82.93%) of MHC
      class I and class II alleles. LsrA epitope was docked with HLA-DR4 and contact
      map were constructed to analyze molecular interaction (docking) studies.
      Simulation search for the binding site for full flexibility of the peptide from
      CABS-dock shows the stable interactions. MD simulation analysis reveals that LsrA
      epitope was binding and interacting firmly with the HLA-DR4. Hence, we are
      proposing that LsrA epitope would be a prominent epitope vaccine for human
      specific pathogen of S. typhi, which requires further steps to be elevated as a
      vaccine drug in near future.

PMID- 30098403
TI  - Meals based on cod or veal in combination with high or low glycemic index
      carbohydrates did not affect diet-induced thermogenesis, appetite sensations, or
      subsequent energy intake differently.
AB  - The objective of this study was to investigate the acute effects of meals
      containing protein from either cod or veal in combination with high or low
      glycemic index (GI) carbohydrates, on diet-induced thermogenesis (DIT) (primary
      endpoint), appetite, energy intake (EI), as well as postpranidal ghrelin,
      glucose, and insulin responses. Twenty-three overweight men and women (mean +/-
      SD age: 30.0 +/- 7.6 y, BMI: 27.2 +/- 1.4 kg/m2) consumed 4 test meals: cod with
      mashed potatoes (high GI carbohydrate), cod with wholegrain pasta (low GI
      carbohydrate), veal with mashed potatoes, and veal with wholegrain pasta (~2010
      kJ, ~25.5 E% protein, ~41.0 E% carbohydrate, ~33.5 E% fat). Energy expenditure
      was measured at baseline and six times postprandially, each lasting 25 min.
      Additionally, appetite sensations were measured every half hour. Arterialized
      venous blood samples were drawn every 20 min until an ad libitum buffet-style
      lunch was served 3.5 h later. DIT did not differ between test meals (P > 0.05),
      and there were no differences in appetite sensations or ad libitum EI (all, P >
      0.05). Meal-time interactions were found for glucose and insulin (P = 0.04 and P
      < 0.001). Pairwise comparisons revealed that glucose and insulin peaks were
      higher after the meals with high GI carbohydrates. No differences were found
      between meals with cod or veal in combination with carbohydrates with low or high
      GI on DIT, appetite sensations, or EI in overweight men and women. However, as
      expected meals with high GI carbohydrates resulted in higher glucose and insulin
      responses compared to meals with low GI carbohydrates regardless of protein
      source.

PMID- 30098404
TI  - Do People With Chronic Musculoskeletal Pain Have Impaired Motor Imagery? A Meta
      analytical Systematic Review of the Left/Right Judgment Task.
AB  - : The left/right judgment task (LRJT) is the most commonly used method of
      assessing motor imagery performance. Abnormally long response times are thought
      to reflect delayed processing of body/spatial representations, and poor accuracy
      is thought to reflect disrupted cortical proprioceptive representations or body
      schema. Slower and less accurate responses on the LRJT have been reported in a
      variety of chronic musculoskeletal pain conditions. To date, no systematic review
      of the literature has been conducted to assess if altered motor imagery
      performance as measured by the LRJT is characteristic of all chronic
      musculoskeletal pain conditions. Therefore, the aim of this study was to conduct
      a comprehensive systematic review and meta-analysis of the literature to answer
      the following question: Do people with chronic musculoskeletal pain have impaired
      left/right body part judgment? Twenty-five studies (2,266 participants) including
      a range of chronic pain populations who undertook an LRJT were identified from
      searches of 8 electronic databases from inception to March 2017. Results indicate
      that chronic musculoskeletal pain conditions affecting the limbs and face (P <=
      .01) are associated with altered motor imagery performance as measured by the
      LRJT. PERSPECTIVES: This review synthesizes evidence of altered motor imagery
      performance using the LRJT across chronic musculoskeletal pain conditions.
      Consistent evidence was found for altered motor imagery performance in peripheral
      pain conditions, but evidence was less consistent for axial conditions. Treatment
      to restore a normal body schema may be beneficial in chronic limb and facial
      pain.

PMID- 30098405
TI  - Associations Between Adolescent Chronic Pain and Prescription Opioid Misuse in
      Adulthood.
AB  - : Prescription opioid misuse is a serious public health concern, yet antecedent
      factors are poorly described. Using data from the National Longitudinal Study of
      Adolescent to Adult Health (N = 14,784), we examined the longitudinal
      relationship between a history of adolescent chronic pain and the odds of
      misusing prescription opioids in adulthood. The primary predictor variable was
      chronic pain status during adolescence. The primary outcome variables were
      prescription opioid misuse during early adulthood and adulthood. Multivariate
      models controlled for known risk factors of opioid misuse, including
      sociodemographics (sex, race, and ethnicity), adolescent mental health symptoms
      (anxiety, depression), adolescent self-reported physical health status,
      adolescent substance use/abuse, childhood trauma, and adult legitimate opioid
      use. We found that adults with a history of adolescent chronic pain were more
      likely to misuse opioids than those without history of chronic pain, even after
      controlling for other known risk factors. Further, we found that among
      individuals with history of adolescent chronic pain that race (white), other
      substance use, and exposure to trauma were risk factors for later opioid misuse.
      Longitudinal associations between adolescent chronic pain and subsequent adult
      prescription opioid misuse highlight the need for early targeted screening and
      prevention efforts that may reduce later opioid misuse. PERSPECTIVE: Using a
      large, nationally representative sample, we found that chronic pain during
      adolescence was an independent risk factor for opioid misuse in adulthood, over
      and above other known risk factors. Furthermore, among those individuals with
      adolescent chronic pain, substance use, exposure to trauma, and race were
      associated with opioid misuse.

PMID- 30098407
TI  - Combination of label-free quantitative proteomics and transcriptomics reveals
      intraspecific venom variation between the two strains of Tetrastichus brontispae,
      a parasitoid of two invasive beetles.
AB  - The venom apparatus is a conserved organ in parasitoids that shows adaptations
      correlated with life-style diversification. Combining transcriptomics and label
      free quantitative proteomics, here we explored the venom apparatus components of
      the endoparasitoid Tetrastichus brontispae (Eulophidae), and provide a comparison
      of the venom apparatus proteomes between its two closely related strains, T.
      brontispae-Octodonta nipae (Tb-On) and T. brontispae-Brontispa longissima (Tb
      Bl). Tb-Bl targets the B. longissima pupa as its habitual host. However, Tb-On is
      an experimental derivative of Tb-Bl, which has been exposed to the O. nipae pupa
      as host consecutively for over 40 generation. Results showed that approximately
      1505 venom proteins were identified in the T. brontispae venom apparatus. The
      extracts contained novel venom proteins, such as 4-coumarate-CoA ligase 4. A
      comparative venom proteome analysis revealed that significant quantitative and
      qualitative differences in venom composition exist between the two strains;
      although the most abundant venom proteins were shared between them. The
      differentially produced proteins were mainly enriched in fatty acid biosynthesis
      and melanotic encapsulation response. Six of these enriched proteins presented
      increased levels in Tb-On, and this result was validated by parallel reaction
      monitoring (PRM) analysis. Overall, our data reveal that venom composition can
      evolve quickly and respond to host selection.

PMID- 30098406
TI  - Combined proteomic and functional analysis reveals rich sources of protein
      diversity in skin mucus and venom from the Scorpaena plumieri fish.
AB  - : The biological activities observed upon envenomation by Scorpaena plumieri
      could be linked to both the venom and the skin mucus. Through a
      proteomic/functional approach we analyzed protein composition and biological
      activities of the venom and skin mucus. We identified 885 proteins: 722 in the
      Venomous Apparatus extracts (Sp-VAe) and 391 in the Skin Mucus extract (Sp-SMe),
      with 494 found exclusively in Sp-VAe, being named S. plumieri Venom Proteins (Sp
      VP), while 228 were found in both extracts. The majority of the many proteins
      identified were not directly related to the biological activities reported here.
      Nevertheless, some were classified as toxins/potentially interesting molecules:
      lectins, proteases and protease inhibitors were detected in both extracts, while
      the pore-forming toxin and hyaluronidase were associated with Sp-VP. Proteolytic
      and anti-microbial activities were linked to both extracts, while the main toxic
      activities - cardiovascular, inflammatory, hemolytic and nociceptive - were
      elicited only by Sp-VAe. Our study provided a clear picture on the composition of
      the skin mucus and the venom. We also show that the classic effects observed upon
      envenomation are produced by molecules from the venomous gland. Our results add
      to the growing catalogue of scorpaeniform fish venoms and their skin mucus
      proteins. SIGNIFICANCE: In this study a large number of proteins - including
      classical and non-classical toxins - were identified in the venomous apparatus
      and the skin mucus extracts of the Scorpaena plumieri fish through shotgun
      proteomic approach. It was shown that the toxic effects observed upon
      envenomation are elicited by molecules originated from the venomous gland. These
      results add to the growing catalogue of scorpaeniform fish venoms and their skin
      mucus proteins - so scarcely explored when compared to the venoms and bioactive
      components of terrestrial animals. Data are available via ProteomeXchange with
      identifier PXD009983.

PMID- 30098408
TI  - Basolateral amygdala inactivation eliminates fear-induced underestimation of time
      in a temporal bisection task.
AB  - We examined interval timing - time perception in the seconds-to-minutes range -
      of the fear-inducing stimulus and the role of the amygdala in this phenomenon.
      Rats were initially trained to perform a temporal bisection task, in which their
      responses to levers A and B were reinforced following 2-s and 8-s tones,
      respectively. After acquisition, the rats were also presented with tones of
      intermediate durations and pressed one of the two levers to indicate whether the
      tone duration was closer to 2 or 8 s. Subsequently, the rats underwent
      differential fear conditioning, in which one frequency tone (conditioned
      stimulus; CS+) was paired with an electric foot shock, whereas another frequency
      tone (CS-) was presented alone. The rats were then infused with artificial
      cerebrospinal fluid (aCSF) or the GABAA agonist muscimol into the bilateral
      basolateral amygdala (BLA) before performing the bisection task with CS+ and CS-.
      In rats infused with aCSF, the psychophysical function shifted rightward in CS+
      relative to that in CS-. Moreover, the point of subjective equality of the CS+
      was higher than that of CS-, suggesting that the duration of the fear -CS was
      perceived as shorter than that of the neutral CS. However, muscimol infusion into
      the BLA abolished this difference, suggesting that BLA inactivation suppresses
      the effect of the fear -CS. Our results demonstrate that normal BLA activity is
      essential for fear-induced underestimation of time.

PMID- 30098409
TI  - The Mastocytosis Society Survey on Mast Cell Disorders: Part 2-Patient Clinical
      Experiences and Beyond.
AB  - BACKGROUND: Mast cell diseases such as mastocytosis and mast cell activation
      syndrome involve abnormal proliferation and/or activation of these cells, leading
      to many clinically relevant symptoms. OBJECTIVE: To determine the characteristics
      and experiences of people known or suspected to have a mast cell disorder, The
      Mastocytosis Society, a US-based patient advocacy, research, and education
      organization, conducted a survey of patients. METHODS: This Web-based survey was
      publicized through specialty clinics and the society's newsletter, Web site, and
      online blogs. Both online and paper copies of the questionnaire were provided
      together with required statements of consent. RESULTS: The first set of results
      from this survey of 420 respondents has been previously published; the second set
      is presented in this article. These results include source(s) of diagnosis,
      clinical and laboratory tests reported, comorbidities, dietary practices,
      possible familial occurrence of mast cell disorders, and perceptions concerning
      mast cell disorder-related medical care needs in the United States. CONCLUSIONS:
      These patient survey results are provided to assist medical professionals in
      learning patients' perceptions of their experiences and to give patients with
      mast cell disorders and caregivers the opportunity to compare experiences with
      those of other affected individuals.

PMID- 30098410
TI  - A Large Single-Hospital Experience Using Drug Provocation Testing and Rapid Drug
      Desensitization in Hypersensitivity to Antineoplastic and Biological Agents.
AB  - BACKGROUND: Large-scale studies of drug provocation testing (DPT) or rapid drug
      desensitization (RDD) for hypersensitivity to antineoplastics and biologicals are
      scarce and limited to a few institutions. OBJECTIVE: Our aim was to review our
      experience with DPT and RDD in a large number of patients with a history of
      hypersensitivity to antineoplastics and biologicals and summarize the practical
      implications of that experience. METHODS: This was a 7-year prospective,
      observational, longitudinal study with reactive patients referred to the
      Desensitization Program at Ramon y Cajal University Hospital (RCUH). Patients
      were selected after following our systematic and validated diagnostic approach
      (clinical history, skin test, risk assessment, specific IgE, DPT) before RDD.
      Candidate patients underwent RDD using the RCUH protocol. Cetuximab reactors
      underwent 1-bag RDDs. RESULTS: A total of 1027 intravenous RDDs were performed
      using the RCUH protocol (399 platins, 395 taxanes, 178 biologicals, 55 other
      drugs), and 1026 were successfully accomplished in the 186 patients (of 515
      referred patients) who met inclusion criteria for RDD. No breakthrough reactions
      occurred in 88% of RDDs. Most breakthrough reactions were mild. A total of 341
      DPTs were performed, and 229 results were negative (67%). DPTs helped exclude
      hypersensitivity in 44% (229 of 515) of referred patients. In addition, 77 one
      bag RDDs were performed in 6 cetuximab-reactive patients. CONCLUSIONS: This
      experience allows us to describe general management plans, as well as specific
      patient phenotypic patterns, predictors for reactions, and risk considerations
      that need a tailored approach (taking into account the 3 prominent drug
      categories: platins, taxanes, and biologicals).

PMID- 30098411
TI  - Manduca sexta hemolymph protease-2 (HP2) activated by HP14 generates
      prophenoloxidase-activating protease-2 (PAP2) in wandering larvae and pupae.
AB  - Melanization is a universal defense mechanism of insects against microbial
      infection. During this response, phenoloxidase (PO) is activated from its
      precursor by prophenoloxidase activating protease (PAP), the terminal enzyme of a
      serine protease (SP) cascade. In the tobacco hornworm Manduca sexta, hemolymph
      protease-14 (HP14) is autoactivated from proHP14 to initiate the protease cascade
      after host proteins recognize invading pathogens. HP14, HP21, proHP1*, HP6, HP8,
      PAP1-3, and non-catalytic serine protease homologs (SPH1 and SPH2) constitute a
      portion of the extracellular SP-SPH system to mediate melanization and other
      immune responses. Here we report the expression, purification, and functional
      characterization of M. sexta HP2. The HP2 precursor is synthesized in hemocytes,
      fat body, integument, nerve and trachea. Its mRNA level is low in fat body of 5th
      instar larvae before wandering stage; abundance of the protein in hemolymph
      displays a similar pattern. HP2 exists as an active enzyme in plasma of the
      wandering larvae and pupae in the absence of an infection. HP14 cleaves proHP2 to
      yield active HP2. After incubating active HP2 with larval hemolymph, we detected
      higher levels of PO activity, i.e. an enhancement of proPO activation. HP2
      cleaved proPAP2 (but not proPAP3 or proPAP1) to yield active PAP2, responsible
      for a major increase in IEARpNA hydrolysis. PAP2 activates proPOs in the presence
      of a cofactor of SPH1 and SPH2. In summary, we have identified a new member of
      the proPO activation system and reconstituted a pathway of HP14-HP2-PAP2-PO.
      Since high levels of HP2 mRNA were present in integument and active HP2 in plasma
      of wandering larvae, HP2 likely plays a role in cuticle melanization during
      pupation and protects host from microbial infection in a soil environment.

PMID- 30098412
TI  - Appraising the uptake and use of the IDEAL Framework and Recommendations: A
      review of the literature.
AB  - INTRODUCTION: Evaluation of new surgical innovations is complex and variably
      regulated, and historically the quality of surgical studies has been criticized.
      The IDEAL (Idea, Development, Exploration, Assessment, Long-term monitoring)
      Framework was established to provide a pathway for evaluating surgical
      innovations at each stage of their development in order to produce high quality
      surgical research. Since the inception of IDEAL in 2009, there has been no
      assessment of its use. In this review, we look at the uptake and usage of IDEAL
      by examining the published literature. METHODS: We conducted a literature search
      to identify all of the publications that cited IDEAL and included only those
      papers that intentionally used IDEAL as part of the study methodology. We then
      characterized these publications by year of publication, specialty, and
      geographical location. We performed a critical appraisal of Stage 1, 2a, and 2b
      studies in order to assess the degree to which authors have correctly followed
      the Framework and Recommendations. RESULTS: We found 790 citations of IDEAL
      publications, and after abstract and full-text screening, 38 prospective studies
      for a surgical innovation that used IDEAL remained. We saw an overall increase in
      the uptake of IDEAL, with a predominance in urology and origin in the United
      Kingdom. The critical appraisal showed that although authors identified their
      project as using IDEAL, they often failed to include key IDEAL characteristics;
      this was especially true for the features unique to IDEAL Stages 2a and 2b.
      CONCLUSION: It is evident from the large number of studies citing IDEAL that the
      importance and challenges of reporting surgical research is well recognized among
      researchers. There is growing enthusiasm for using IDEAL but the current level of
      understanding of the Recommendations is low. Clearer and more comprehensive
      explanation of the application of the IDEAL Framework and Recommendations is
      needed to guide surgical researchers undertaking IDEAL based studies of surgical
      innovations.

PMID- 30098413
TI  - Pyomyoma After Uterine Artery Embolization: Laparotomy Avoided by In-Bag
      Morcellation.
AB  - We report a case of a pyomyoma in which in-bag morcellation allowed for a total
      laparoscopic hysterectomy instead of laparotomy, which has been recognized as the
      standard of care to avoid the spread of infection from morcellation. A 45-year
      old multiparous woman presented with sepsis, pelvic pain, and leukocytosis at 1
      month after undergoing uterine artery embolization for symptomatic uterine
      leiomyoma. Pelvic computed tomography scan revealed a 9-cm suspected pyomyoma. A
      total hysterectomy was performed using a laparoscopic approach with in-bag
      morcellation. The intervention was successful, and the postoperative course was
      uneventful. The patient was discharged on postoperative day 1 and was well at 2
      months after surgery.

PMID- 30098414
TI  - Expression, purification and biological activity of monomeric insulin precursors
      from methylotrophic yeasts.
AB  - The methylotrophic yeasts Pichia pastoris and Hansenula polymorpha have been used
      for the production of recombinant monomeric insulin precursor (MIP). Recombinant
      plasmids with one, two and four cassettes of the MIP gene have been successfully
      constructed in the pPICZalphaA expression vector to study the effects of gene
      copy number on MIP production. The MIP protein can be detected by dot-blot
      analysis from the culture broth of P. pastoris KM71H 24 h after placement in MMH
      induction medium. The secretion levels of MIP protein in culture broth at 72 h
      after induction indicated that P. pastoris KM71H with one cassette of the MIP
      gene had highest MIP protein levels (4.19 +/- 0.96 mg L-1). The transcription
      levels of the MIP gene increased proportionately with copy number. However, the
      amount of secreted MIP protein showed no correlation. The MIP molecular mass was
      5756.951 Da, as confirmed by typical MALDI-TOF mass spectrometry. The MIP protein
      in culture broth was purified by two steps purification including SP Sepharose
      Fast Flow chromatography followed by ultrafiltration (10 kDa MW cutoff). The
      percentage of MIP recovery after the two-step purification was 70%, with a single
      band in a native-PAGE. The biological activity of tryptic hydrolyzed MIP was
      determined via the expression of the glucose transporter 4 gene (GLUT4) in H9c2
      (2-1) cell line by RT-qPCR, and the results demonstrated that the MIP protein can
      induce glucose uptake and upregulation of GLUT4 mRNA transcription at 3 h and
      that this activity was related to Humalog(r) insulin.

PMID- 30098415
TI  - Is seashell powder suitable for phosphate recovery from fermentation broth?
AB  - This communication elaborates on the use of seashell powder (SP) for the removal
      of phosphate from lactic acid-containing fermentation broth. Despite extensive
      past research regarding the application of SP for phosphate removal from
      wastewater, no information is available for solutions containing various organic
      compounds. In order to fill this knowledge gap, tests were performed with pure
      phosphate solution (PPS) and PPS containing 0.83 M of three alcohols, ethanol,
      propanol or 1,2-propanediol, or 0.83 M of three organic acids, acetic, propionic
      or lactic acid. Furthermore, a real fermentation broth (RFB) obtained from the
      fermentative production of lactic acid from food waste was tested. Using 4.8 g
      SP, more than 95% of phosphate, present at an initial concentration of 50 mg L-1,
      could be removed from PPS and PPS containing alcohols after 120 min. The presence
      of organic acids reduced the removal capacity of SP and only 55%-73% of the
      phosphate initially present was removed. The presence of lactic acid also
      substantially affected the removal of phosphate from RFB when 132 mg L-1
      phosphate was initially present: after 120 min, only 28.6 mg L-1 of phosphate had
      been removed. The results indicate the use of SP for phosphate removal from
      fermentation broth, contributing to multi-component utilization of fermentation
      broth. However, the effects of respective fermentation products on removal
      capacity should first be tested.

PMID- 30098416
TI  - Bioactive molecules derived from smoke and seaweed Ecklonia maxima showing
      phytohormone-like activity in Spinacia oleracea L.
AB  - Bioactive compounds such as karrikinolide (KAR1 from smoke) and eckol (from the
      seaweed Ecklonia maxima) show promising effects on several important crop plants.
      These plant growth-stimulating organic biomolecules, along with crude extracts
      (smoke-water and Kelpak(r) product prepared from Ecklonia maxima), were tested on
      spinach plants. Eckol sprayed at 10-6 M significantly increased all the growth
      and biochemical parameters examined compared to control spinach plants. All
      tested plant growth biostimulants significantly increased total chlorophyll,
      carotenoids and protein content of spinach leaves. The cytokinin profile of
      spinach plants was also determined. Cis-zeatin, dihydrozeatin and
      isopentenyladenine types of cytokinins were promoted by both smoke- and seaweed
      based biostimulants. In comparison to the control plants, the level of free
      sinapic acid was greater in all spinach plants treated with these biostimulants.
      The application of these biostimulants can help spinach crop by improving growth,
      yield and nutritional quality; moreover, they are organic and cost-effective.

PMID- 30098417
TI  - Statin treatment reduces matrix degradation capacity of proinflammatory polarized
      macrophages.
AB  - BACKGROUND AND AIMS: Macrophages are versatile immune cells involved in tissue
      degradation and remodeling. Proinflammatory macrophages have the highest capacity
      of matrix degradation and proteolysis. Within atherosclerotic lesions,
      proinflammatory macrophages are associated with unstable plaques. Statins have
      been demonstrated to increase plaque stability. Possible changes of polarized
      macrophage tissue degradation behavior under statin treatment are currently
      unknown. METHODS: Polarized macrophages were tested in vitro for matrix
      degradation capacity with or without statin treatment. RESULTS: Proinflammatory
      macrophages show high matrix degradation capacity, which is lost after statin
      treatment. Statin concentrations were within a physiological range and did not
      influence overall macrophage polarization. Proinflammatory macrophages showed
      however a loss of filopodia where activators of MMPs are located. Loss of matrix
      degradation in proinflammatory macrophages was associated with changes of MMP14
      activation and loss of uPAR localization at filopodia. Supplementation of
      mevalonate restored localization of uPAR to cellular protrusions and matrix
      degradation capacity. CONCLUSION: Statins reduce the matrix degradation potential
      of proinflammatory macrophages by reducing uPAR localization to cellular
      filopodia and reducing intracellular MMP14 activation.

PMID- 30098418
TI  - The trabecular bone score: Relationships with trabecular and cortical
      microarchitecture measured by HR-pQCT and histomorphometry in patients with
      chronic kidney disease.
AB  - The trabecular bone score (TBS) is a novel tool using grayscale variograms of the
      lumbar spine bone mineral density (BMD) to assess trabecular bone
      microarchitecture. Studies in patients with chronic kidney disease (CKD) suggest
      it may be helpful in assessing fracture risk. However, TBS has not been validated
      as a measure of trabecular architecture against transiliac bone biopsy with
      histomorphometry in CKD patients. We hypothesized that TBS would reflect
      trabecular architecture at the iliac crest in CKD patients. We obtained
      tetracycline double labeled transiliac crest bone biopsy, areal BMD of the spine,
      total hip, femoral neck (FN) and spine TBS by dual energy X-ray absorptiometry
      (DXA), and cortical and trabecular volumetric density and microarchitecture by
      high resolution peripheral quantitative computed tomography (HR-pQCT) in CKD
      patients from two centers: twenty-two patients from Columbia University Medical
      Center, USA and thirty patients from Hospital das Clinicas - Universidade de Sao
      Paulo, Brazil. Two patients were excluded for outlier status. Univariate and
      multivariate relationships between TBS and measures from DXA, HR-pQCT and
      histomorphometry were determined. Patients were 50.2 +/- 15.8 years old, 23 (46%)
      were men, and 33 (66%) were on dialysis. TBS was <1.31 in 21 (42%) patients and
      22%, 14% and 10% had T-scores <= -2.5 at spine, FN and total hip respectively. In
      univariate regression, TBS was significantly associated with trabecular bone
      volume (BV/TV), trabecular width (Tb.Wi), trabecular spacing, cortical width but
      not with trabecular number or cortical porosity. FN Z-score and height were also
      associated with cancellous BV/TV and Tb.Wi, In multivariate analysis, TBS
      remained an independent predictor of BV/TV and Tb.Wi. There were no relationships
      between TBS and dynamic parameters from histomorphometry. These data suggest that
      TBS reflected trabecular microarchitecture and cortical width measured by bone
      biopsy in CKD patients. Future studies should address its utility in the
      identification of CKD patients who may benefit from fracture prevention
      strategies.

PMID- 30098419
TI  - Prostate cancer sheds the alphavbeta3 integrin in vivo through exosomes.
AB  - The alphavbeta3 integrin has been shown to promote aggressive phenotypes in many
      types of cancers, including prostate cancer. We show that GFP-labeled alphavbeta3
      derived from cancer cells circulates in the blood and is detected in distant
      lesions in NOD scid gamma (NSG) mice. We, therefore, hypothesized that
      alphavbeta3 travels through exosomes and tested its levels in pools of vesicles,
      which we designate extracellular vesicles highly enriched in exosomes (ExVs), and
      in exosomes isolated from the plasma of prostate cancer patients. Here, we show
      that the alphavbeta3 integrin is found in patient blood exosomes purified by
      sucrose or iodixanol density gradients. In addition, we provide evidence that the
      alphavbeta3 integrin is transferred through ExVs isolated from prostate cancer
      patient plasma to beta3-negative recipient cells. We also demonstrate the
      intracellular localization of beta3-GFP transferred via cancer cell-derived ExVs.
      We show that the ExVs present in plasma from prostate cancer patients contain
      higher levels of alphavbeta3 and CD9 as compared to plasma ExVs from age-matched
      subjects who are not affected by cancer. Furthermore, using PSMA antibody-bead
      mediated immunocapture, we show that the alphavbeta3 integrin is expressed in a
      subset of exosomes characterized by PSMA, CD9, CD63, and an epithelial-specific
      marker, Trop-2. Finally, we present evidence that the levels of alphavbeta3,
      CD63, and CD9 remain unaltered in ExVs isolated from the blood of prostate cancer
      patients treated with enzalutamide. Our results suggest that detecting exosomal
      alphavbeta3 integrin in prostate cancer patients could be a clinically useful and
      non-invasive biomarker to follow prostate cancer progression. Moreover, the
      ability of alphavbeta3 integrin to be transferred from ExVs to recipient cells
      provides a strong rationale for further investigating the role of alphavbeta3
      integrin in the pathogenesis of prostate cancer and as a potential therapeutic
      target.

PMID- 30098420
TI  - The Receptor for Hyaluronan-Mediated Motility (CD168) promotes inflammation and
      fibrosis after acute lung injury.
AB  - Acute lung injury results in early inflammation and respiratory distress, and
      later fibrosis. The glycosaminoglycan hyaluronan (HA) and the Receptor for
      Hyaluronan-Mediated Motility (RHAMM, CD168) have been implicated in the response
      to acute lung injury. We hypothesized that, compared to wild type (WT) mice,
      RHAMM knockout (KO) mice would be protected from, whereas mice with macrophage
      specific transgenic overexpression of RHAMM (TG) would have worse inflammation,
      respiratory distress and fibrosis after intratracheal (IT) bleomycin. Compared to
      WT mice, 10 days after IT bleomycin, RHAMM KO mice had less weight loss, less
      increase in respiratory rate, and fewer CD45+ cells in the lung. At day 28,
      compared to injured WT animals, injured RHAMM KO mice had lower M1 macrophage
      content, as well as decreased fibrosis as determined by trichrome staining,
      Ashcroft scores and lung HPO content. Four lines of transgenic mice with
      selective overexpression of RHAMM in macrophages were generated using the
      Scavenger Receptor A promoter driving a myc-tagged full length RHAMM cDNA.
      Baseline expression of RHAMM and CD44 was the same in WT and TG mice. By flow
      cytometry, TG bone marrow-derived macrophages (BMDM) had increased cell surface
      RHAMM and myc, but equal CD44 expression. TG BMDM also had 2-fold increases in
      both chemotaxis to HA and proliferation in fetal bovine serum. In TG mice,
      increased inflammation after thioglycollate-induced peritonitis was restricted to
      macrophages and not neutrophils. For lung injury studies, non-transgenic mice
      given bleomycin had respiratory distress with increased respiratory rates from
      day 7 to 21. However, TG mice had higher respiratory rates from 4 days after
      bleomycin and continued to increase respiratory rates up to day 21. At 21 days
      after IT bleomycin, TG mice had increased lung macrophage accumulation. Lavage HA
      concentrations were 6-fold higher in injured WT mice, but 30-fold higher in
      injured TG mice. At 21 days after IT bleomycin, WT mice had developed fibrosis,
      but TG mice showed exaggerated fibrosis with increased Ashcroft scores and HPO
      content. We conclude that RHAMM is a critical component of the inflammatory
      response, respiratory distress and fibrosis after acute lung injury. We speculate
      that RHAMM is a potential therapeutic target to limit the consequences of acute
      lung injury.

PMID- 30098421
TI  - Assessing mitochondrial heteroplasmy using next generation sequencing: A note of
      caution.
AB  - The mitochondrial genome has recently become the focus of several high-impact
      next-generation sequencing studies investigating the effect of mutations in
      disease and assessing the efficacy of mitochondrial replacement therapies.
      However, these studies have failed to take into consideration the capture of
      recurring translocations of mitochondrial DNA to the nuclear genome, known as
      nuclear mitochondrial sequences (NUMTs), continuing to align sequence data to the
      revised Cambridge reference sequence alone. Here, using different mtDNA
      enrichment techniques and a variety of tissues, we demonstrate that NUMTs are
      present in sequence data and that, dependent upon downstream analysis, are at a
      level which affects variant calling.

PMID- 30098422
TI  - Cell-free mitochondrial DNA in progressive multiple sclerosis.
AB  - Recent studies have linked cell-free mitochondrial DNA (ccf-mtDNA) to
      neurodegeneration in both Alzheimer's and Parkinson's disease, raising the
      possibility that the same phenomenon could be seen in other diseases which
      manifest a neurodegenerative component. Here, we assessed the role of circulating
      cell-free mitochondrial DNA (ccf-mtDNA) in end-stage progressive multiple
      sclerosis (PMS), where neurodegeneration is evident, contrasting both ventricular
      cerebral spinal fluid ccf-mtDNA abundance and integrity between PMS cases and
      controls, and correlating ccf-mtDNA levels to known protein markers of
      neurodegeneration and PMS. Our data indicate that reduced ccf-mtDNA is a
      component of PMS, concluding that it may indeed be a hallmark of broader
      neurodegeneration.

PMID- 30098423
TI  - Bone disorders associated with diabetes mellitus and its treatments.
AB  - Both type 1 and type 2 diabetes mellitus are associated with bone disorders,
      albeit via different mechanisms. Early studies in patients with type 1 diabetes
      suggested a 10-fold increase in the hip fracture risk compared to non-diabetic
      controls. Meta-analyses published more recently indicate a somewhat smaller risk
      increase, with odds ratios of 6 to 7. Diminished bone mineral density is among
      the contributors to the increased fracture risk. Both types of diabetes are
      associated with decreased bone strength related to low bone turnover. The
      multiple and interconnected pathophysiological mechanisms underlying the bone
      disorders seen in type 1 diabetes include insulin deficiency, accumulation of
      advanced glycation end products, bone microarchitecture alterations, changes in
      bone marrow fat content, low-grade inflammation, and osteocyte dysfunction. The
      bone alterations are less severe in type 2 diabetes. Odds ratios for hip
      fractures have ranged across studies from 1.2 to 1.7, and bone mineral density is
      higher than in non-diabetic controls. The odds ratio is about 1.2 for all bone
      fragility fractures combined. The pathophysiological mechanisms are complex,
      particularly as obesity is very common in patients with type 2 diabetes and is
      itself associated with an increased risk of fractures at specific sites (humerus,
      tibia, and ankle). The main mechanisms underlying the bone fragility are an
      increase in the risk of falls, sarcopenia, disorders of carbohydrate metabolism,
      vitamin D deficiency, and alterations in cortical bone microarchitecture and bone
      matrix. The medications used to treat both types of diabetes do not seem to play
      a major role. Nevertheless, thiazolidinediones and, to a lesser extent, sodium
      glucose cotransporter inhibitors may have adverse effects on bone, whereas
      metformin may have beneficial effects. For the most part, the standard management
      of bone fragility applies to patients with diabetes. However, emphasis should be
      placed on preventing falls, which are particularly common in this population.
      Finally, there is some evidence to suggest that anti-fracture treatments are
      similarly effective in patients with and without diabetes.

PMID- 30098424
TI  - Sarcopenia.
AB  - Sarcopenia is defined as a combination of low muscle mass with low muscle
      function. The term was first used to designate the loss of muscle mass and
      performance associated with aging. Now, recognized causes of sarcopenia also
      include chronic disease, a physically inactive lifestyle, loss of mobility, and
      malnutrition. Sarcopenia should be differentiated from cachexia, which is
      characterized not only by low muscle mass but also by weight loss and anorexia.
      Sarcopenia results from complex and interdependent pathophysiological mechanisms
      that include aging, physical inactivity, neuromuscular compromise, resistance to
      postprandial anabolism, insulin resistance, lipotoxicity, endocrine factors,
      oxidative stress, mitochondrial dysfunction, and inflammation. The prevalence of
      sarcopenia ranges from 3% to 24% depending on the diagnostic criteria used and
      increases with age. Among patients with rheumatoid arthritis 20% to 30% have
      sarcopenia, which correlates with disease severity. Sarcopenia exacts a heavy
      toll of functional impairment, metabolic disorders, morbidity, mortality, and
      healthcare costs. Thus, the consequences of sarcopenia include disability,
      quality of life impairments, falls, osteoporosis, dyslipidemia, an increased
      cardiovascular risk, metabolic syndrome, and immunosuppression. The adverse
      effects of sarcopenia are particularly great in patients with a high fat mass, a
      condition known as sarcopenic obesity. The diagnosis of sarcopenia rests on
      muscle mass measurements and on functional tests that evaluate either muscle
      strength or physical performance (walking, balance). No specific biomarkers have
      been identified to date. The management of sarcopenia requires a multimodal
      approach combining a sufficient intake of high-quality protein and fatty acids,
      physical exercise, and antiinflammatory medications. Selective androgen receptor
      modulators and anti-myostatin antibodies are being evaluated as potential
      stimulators of muscle anabolism.

PMID- 30098425
TI  - Long non-coding RNA THOR promotes cell proliferation and metastasis in
      hepatocellular carcinoma.
AB  - Long non-coding RNAs (lncRNAs) have been demonstrated to be involved in the
      development and progression of multiple cancers by previous studies. Recently, a
      novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding
      RNA), was characterized in human cancers and shown to exhibit an oncogenic role.
      However, the role of THOR in hepatocellular carcinoma (HCC) is still unclear. In
      this study, we found that THOR was relatively highly expressed in human HCC
      tissues and cell lines. Notably, high THOR expression was associated with worse
      prognosis. THOR depletion resulted in significant inhibition of the growth and
      metastasis of HCC cells. Mechanistically, THOR drives HCC cell progression via
      the PTEN/AKT pathway. Moreover, the specific PI3-K inhibitor LY294002 abolished
      the discrepancy in the growth and metastatic capacity between THOR-silenced HCC
      cells and control cells, which further confirmed that AKT was required in THOR
      driven HCC cell growth and metastasis. Taken together, our results suggest that
      THOR could promote HCC cell growth and metastasis by amplifying PTEN/AKT
      signaling and may be a new therapeutic target and predictive factor for HCC.

PMID- 30098426
TI  - LncRNA GACAT3 acts as a competing endogenous RNA of HMGA1 and alleviates
      cucurbitacin B-induced apoptosis of gastric cancer cells.
AB  - Long non-coding RNAs (lncRNAs) have been demonstrated to perform important roles
      in cancer development. Previously, we have shown that lncRNA gastric cancer
      associated transcript 3 (GACAT3) is overexpressed in gastric cancer and acts as a
      downstream target of interleukin 6/signal transducer and activator of
      transcription 3 (IL-6/STAT3) signaling. However, the role of GACAT3 in regulating
      gastric cancer cell growth remains unclear. In this study, we demonstrate that
      GACAT3 acts as a competing endogenous RNA of high mobility group A1 (HMGA1), a
      typical oncogene that is overexpressed in most types of cancer, based on a search
      for common miRNA-binding sites and on experiments involving in vitro cell
      transfection with synthesized miRNA mimics. Furthermore, knockdown of GACAT3 by
      its specific siRNA resulted in significantly decreased cell proliferation in
      gastric cancer cells, similar to the effect of an HMGA1 knockdown. Moreover,
      GACAT3 overexpression alleviated the apoptosis induced by cucurbitacin B, which
      is a widely used anticancer drug. Mechanistically, GACAT3 amplified STAT3
      expression and decreased the level of the apoptosis gene bcl-2-associated X
      protein (BAX). Thus, our study provides fundamental information regarding GACAT3,
      which could be a valuable target for gastric cancer therapy.

PMID- 30098427
TI  - Molecular characterization of a novel ovodefensin gene in chickens.
AB  - Host defense peptides (HDPs) represent a large group of diverse small peptides
      that play important roles in host defense and disease resistance. In vertebrates,
      one of the main types of HDPs belong to defensins, which are less than 100 amino
      acid residues and characterized by a highly conserved motif of cysteine residues.
      Recently, a subfamily of defensins, namely ovodefensins (OvoDs), has been
      identified in birds and reptiles. However, both their family members and
      evolutionary relationships remain unclear. In the present study, we cloned and
      characterized a novel gene namely OvoDBbeta in chickens. Our results showed that
      the full length of chicken OvoDBbeta mRNA contains 344 bp nucleotides and encodes
      a 61-amino acid protein. We further revealed that the mRNA of OvoDBbeta is
      abundant in the oviduct of laying hens but absent in many other tissues.
      Additionally, sequences comparison and analyses suggested that OvoDBbeta is
      orthologous to the gene previously known as zebra finch OvoDB1, albeit it might
      exhibit specific structures. Furthermore, both OvoDBalpha and OvoDBbeta were
      existent in the genome of each bird, implying that two types of OvoDBs sharing
      same cysteine motif have already emerged before the species divergence. More
      importantly, recombinant OvoDBbeta mature peptide exerted antibacterial activity
      against Escherischia coli (CICC23657 strain) in vitro. These results collectively
      indicated that the putative sequence, namely chicken OvoDBbeta, is a function
      gene with potential antimicrobial property. Discovery and function
      characterization of novel HDP genes may help us develop novel antimicrobial
      agents in the future.

PMID- 30098428
TI  - LINC00052/miR-101-3p axis inhibits cell proliferation and metastasis by targeting
      SOX9 in hepatocellular carcinoma.
AB  - Long non-coding RNAs (lncRNAs) have emerged as critical regulators in a variety
      of diseases, including many tumors, such as hepatocellular carcinoma (HCC).
      However, the function and mechanisms responsible for these molecules in HCC are
      not thoroughly understood. In our previous study, we found that LINC00052 was
      acted as a tumor suppressor in HCC. In this study, we performed transcription
      microarray analysis to investigate the target gene of LINC00052, and found that
      knockdown of LINC00052 significantly increased the expression of SRY-related HMG
      box gene 9 (SOX9), which plays an oncogenic role in HCC. Moreover, luciferase
      reporter assay revealed that LINC00052 promoted miR-101-3p expression by
      enhancing its promoter activity. In addition, online database analysis tools and
      luciferase assays showed that miR-101-3p could target SOX9. Quantitative real
      time polymerase chain reaction (qRT-PCR) demonstrated that miR-101-3p was
      downregulated in HCC tissues and HCC cell lines. And we found a positive
      relationship between LINC00052 and miR-101-3p, and a negative relationship
      between miR-101-3p and SOX9 in HCC tissues. Besides, miR-101-3p was involved in
      LINC00052 inhibits HCC cells proliferation and metastasis. At the molecular
      level, LINC00052 downgulated SOX9 to inhibit HCC cells proliferation and
      metastasis by interacting with miR-101-3p. It might be a potential application
      for HCC therapy.

PMID- 30098429
TI  - Comprehensive and in-depth analysis of microRNA and mRNA expression profile in
      salivary adenoid cystic carcinoma.
AB  - OBJECTIVES: To conduct an integrated analysis of microRNA and mRNA expression
      profile and further discover vital molecules to uncover novel pathogenic
      mechanisms in salivary adenoid cystic carcinoma (SACC). MATERIALS AND METHODS:
      MicroRNA and mRNA expression profiles were obtained from six paired primary SACC
      tumors and corresponding adjacent normal glands using high-throughput next
      generation sequencing technology followed by an overall integrated bioinformatics
      analysis and subsequently molecular biology techniques validation. RESULTS:
      Compared with adjacent noncancerous normal gland, 2107 significant differentially
      expressed mRNA were determined in SACC. Gene ontology and KEGG pathway analysis
      suggested that the differentially expressed genes were relevant to many
      significant biological implications. Venn diagram analysis of differentially
      expressed genes in different group identified 29 differentially expressed
      overlapping mRNA. 40 differentially expressed microRNAs were also identified in
      SACC. Furthermore, integrated analysis of microRNA and mRNA expression profiles
      recognized a core microRNA-mRNA regulatory network and unmasked many novel genes
      including SCUBE3, CA6, hsa-miR-885-5p and other molecules which may play an
      essential role in the carcinogenesis of SACC. Also, Q-PCR and
      immunohistochemistry results reveal the high expression and distribution of
      SCUBE3 in SACC and dual luciferase reporter assay also preliminarily validated
      that SCUBE3 was a target of hsa-miR-885-5p. CONCLUSION: Contemporary
      microRNA/mRNA analysis have uncovered many mRNAs and microRNAs worthy further
      exploration in SACC. These are bound to help us shed light on the overall genetic
      background of SACC and further elucidate the potential molecular mechanism of
      SACC.

PMID- 30098430
TI  - Effect of silencing microRNA-508 by STTM on melanogenesis in alpaca (Vicugna
      pacos).
AB  - It has been demonstrated that microRNAs (miRNAs) play important roles in the
      regulation of melanogenesis and hair color in mammals. Short tandem target mimic
      (STTM) has been used to effectively block small RNA functions in plants and
      animals. We previously showed that miR508-3p plays a functional role in
      regulating melanogenesis in alpaca melanocytes by directly targeting
      microphthalmia (MITF). To verify the effect of miR-508-3p function on
      melanogenesis in alpaca melanocytes, miR-508-3p was blocked using STTM technology
      in the present research. miR508-3p was predicted to target the gene encoding SRY
      box6 (SOX6) by bioinformatics. The luciferase reporter assay indicated that
      miR508-3p regulates SRY-box6 (SOX6) expression by targeting its 3'UTR. Here, STTM
      miR508-3p overexpression in alpaca melanocytes blocked the expression of miR-508
      3p and up-regulated SOX6 expression at both the mRNA and protein levels,
      resulting in increasing the expression of key melanogenic genes, including cAMP
      responsive element (CRE) binding protein (CREB), MITF, tyrosinase (TYR) and
      tyrosinase-related protein 1 and 2 (TYRP1 and TYRP2). STTM-miR508-3p
      overexpression in melanocytes also resulted in increased melanin production,
      including total alkali soluble melanogenesis (ASM), eumelanogenesis (EM) and
      pheomelanogenesis (PM). Additionally, we identified melanin granules in alpaca
      melanocytes transfected with STTM-miR508-3p under Fontana-Masson staining. These
      results suggest that STTM-miR508-3p could up-regulate melanogenesis by
      effectively blocking miR508-3p.

PMID- 30098431
TI  - Long noncoding RNA SNHG12 facilitates the tumorigenesis of glioma through miR-101
      3p/FOXP1 axis.
AB  - The increasing vital roles of long coding RNA (lncRNAs) in the glioma
      tumorigenesis have renewedly and roundly recognized. Nevertheless, the in-depth
      that lncRNAs modulate the gliomagenesis is still elusive. In this research, we
      focus on the functional study of lncRNA SNHG12 in the glioma pathogenesis. SNHG12
      expression was enhanced and high-expressed in the glioma clinical tissue samples
      and cell lines, especially in the advanced clinical grade. In functional study,
      knockdown of SNHG12 impaired the proliferation, induced the apoptosis in vitro
      and, meanwhile, inhibited the tumor growth in vivo. In mechanistic study, it was
      found that SNHG12 harbored the complementary binding sites with miR-101-3p at 3'
      UTR, acting as a miRNA 'sponge'. Furthermore, miR-101-3p also targeted the 3'-UTR
      of FOXP1 mRNA. The three elements construct the SNHG12/miR-101-3p/FOXP1 axis.
      Overall, we confirmed a functional regulatory pathway that SNHG12 and miR-101-3p
      regulated the expression of FOXP1 in glioma cells, forming the SNHG12/miR-101
      3p/FOXP1 pathway. This finding might act as a valuable target for glioma.

PMID- 30098432
TI  - Transcriptome analysis of Corynebacterium pseudotuberculosis biovar Equi in two
      conditions of the environmental stress.
AB  - Corynebacterium pseudotuberculosis has been widely studied in an effort to
      understand its biological evolution. Transcriptomics has revealed possible
      candidates for virulence and pathogenicity factors of strain 1002 (biovar Ovis).
      Because C. pseudotuberculosis is classified into two biovars, Ovis and Equi, it
      was interesting to assess the transcriptional profile of biovar Equi strain 258,
      the causative agent of ulcerative lymphangitis. The genome of this strain was re
      sequenced; the reassembly was completed using optical mapping technology, and the
      sequence was subsequently re-annotated. Two growth conditions that occur during
      the host infection process were simulated for the transcriptome: the osmotic and
      acid medium. Genes that may be associated with the microorganism's resilience
      under unfavorable conditions were identified through RNAseq, including genes
      present in pathogenicity islands. The RT-qPCR was performed to confirm the
      results in biological triplicate for each condition for some genes. The results
      extend our knowledge of the factors associated with the spread and persistence of
      C. pseudotuberculosis during the infection process and suggest possible avenues
      for studies related to the development of vaccines, diagnosis, and therapies that
      might help minimize damage to agribusinesses.

PMID- 30098433
TI  - Oxidative stress and bronchopulmonary dysplasia.
AB  - With the progress of modern medicine, oxygen therapy has become a crucial measure
      for the treatment of premature infants. As an environmental stimulus, in the
      normal development of lungs, oxygen plays a very important regulatory role.
      However, the problem is that long-term exposure to hyperoxia can interfere with
      the development of lungs, leading to irreversible developmental abnormalities.
      Now, the incidence of bronchopulmonary dysplasia (BPD) is increasing year by
      year. The existing related research shows that although BPD is a multi-factor
      triggered disease, its main risk factors are the premature exposure to hyperoxia
      and the role of reactive oxygen species (ROS). As for premature infants,
      especially very premature babies and those with very low birth weight, prolonged
      exposure to high oxygen can affect and alter the normal developmental
      trajectories of lung tissue and vascular beds, triggering developmental
      disorders, such as BPD. In the relevant studies about human BPD, a large number
      of them support that ROS is associated with impaired lung development. Neonates,
      due to the damage in the development of alveolar, are specific to hyperoxia
      induced inflammatory damage. This review while focusing on the role of oxidative
      stress in the pathogenesis of BPD, suggests that antioxidant measures may be
      effective to guard against BPD of preterm infants.

PMID- 30098434
TI  - Downregulation of circular RNA hsa_circ_0000144 inhibits bladder cancer
      progression via stimulating miR-217 and suppressing RUNX2 expression.
AB  - Although increasing aberrantly expressed circular RNAs (circRNAs) have been
      identified among many human cancer tissues, their roles in tumor progression
      still remain largely unknown. In bladder cancer, the function of hsa_circ_0000144
      has not been reported. In our study, we found hsa_circ_0000144 as a novel
      oncogene in bladder cancer by bioinformatics analysis. We found that
      hsa_circ_0000144 expression was significantly upregulated in bladder cancer
      tissues compared with adjacent normal tissues, and its high expression was
      related with poor prognosis. Additionally, knockdown of hsa_circ_0000144
      remarkably suppressed the proliferation and invasion of bladder cancer cells in
      vitro. Hsa_circ_0000144 silence also led to reduced tumor volumes in vivo. In
      mechanism, we found that hsa_circ_0000144 was a sponge of miR-217 while miR-217
      targeted RUNX2. Our results indicated that the expression of miR-217 was
      inversely correlated with that of both hsa_circ_0000144 and RUNX2 in bladder
      cancer tissues. Rescue assays showed that either inhibition of miR-217 or
      restoration of RUNX2 reversed the suppressive effects of hsa_circ_0000144
      knockdown on bladder cancer cell proliferation and invasion. Taken together,
      these findings demonstrated that hsa_circ_0000144 exerts oncogenic roles in
      bladder cancer via repressing miR-217 to facilitate RUNX2 expression.

PMID- 30098435
TI  - Human Placenta Simulator for Intracranial-Intracranial Bypass: Vascular Anatomy
      and 5 Bypass Techniques.
AB  - BACKGROUND: Intracranial-intracranial (IC-IC) bypass surgery involves the use of
      significant technical bimanual skills. Indications for this procedure are
      limited, so training in a simulator with brain vessels similarity could maintain
      microsurgical dexterity. Our goal is to describe the human placenta vascular
      anatomy to guide IC-IC bypasses apprenticeship. METHODS: Human placenta vascular
      anatomy was reported and validated with comparison to brain main vessels after
      studying the vascular tree of 100 placentas. Five simulated IC-IC bypasses (end
      to end, end to lateral, lateral to lateral, aneurysm bridge, and aneurysm exiting
      branch transposition) were developed and construct and concurrent validated.
      Statistical analysis using the t variance test was performed with a confidence
      interval of 0.95. RESULTS: A total of 1200 placenta vessels were used for test
      retest validation with a reliability index of 0.95. All 100 human placentas were
      suitable to perform the 5 different bypasses. Construct validity showed a P <
      0.005. Concurrent validity highlighted the technical differences among
      simulators. CONCLUSIONS: An ex vivo bypass model offers great similarity to main
      brain vessels with the possibility to practice a variety of IC-IC bypass
      techniques in a single simulator. Placenta vascular anatomy knowledge can improve
      laboratory microsurgical training.

PMID- 30098436
TI  - Pediatric Intracranial Anaplastic Gangliogliomas: Illustrative Case and
      Systematic Review.
AB  - OBJECTIVE: We present an illustrative case of pediatric intracranial anaplastic
      ganglioglioma and systematically reviewed the current reported data of anaplastic
      ganglioglioma in the pediatric population. METHODS: A comprehensive literature
      search for our review was conducted using PubMed, Scopus, Web of Science,
      PsycINFO, Cochrane, and Embase databases. The search terms included
      "ganglioglioma," "anaplastic," "pediatrics," "children," and "intracranial." We
      used no limitations for date, type, or language. Reports of pediatric patients
      (age <19 years) with intracranial anaplastic gangliogliomas were included.
      Baseline patient demographic characteristics, clinical presentations, imaging
      characteristics, management strategies, and outcomes data were extracted.
      RESULTS: We included 24 studies involving 34 patients in the quantitative
      synthesis. The mean patient age was 9.18 +/- 5.46 years (range, 0.16-18). A male
      predominance was observed (approximate male/female ratio, 1.61:1). Increased
      intracranial pressure was the most common symptom (n = 19; 55%), followed by
      seizures (n = 11; 32%). These tumors were most often found in the supratentorial
      compartment (n = 26; 76%). All 34 patients had undergone surgical removal. The
      mean follow-up was 22.2 months (range, 2-72). The mean overall survival duration
      was 43 months (95% confidence interval, 32.45%-55.31%; 1- and 3-year overall
      survival, 76.6% and 45.5%, respectively). The median event-free survival was 34
      months (95% confidence interval, 10.6%-57.3%; 1- and 3-year event-free survival
      rate, 76.6% and 42.4%, respectively). CONCLUSIONS: Our results contribute to our
      understanding of the characteristics of this rare malignant tumor and show that
      anaplastic ganglioglioma should be considered in the differential diagnosis of
      intracranial tumors in pediatric patients.

PMID- 30098437
TI  - Decompression by Cutting the Tentorium for Trigeminal Neuralgia Caused by
      Vertebrobasilar Dolichoectasia.
AB  - BACKGROUND: Trigeminal neuralgia caused by vertebrobasilar dolichoectasia (VBD)
      is rare and challenging to treat. Some authors have reported techniques for
      treating trigeminal neuralgia caused by VBD using various kinds of objects
      including clips, Proline slings, and titanium plates. METHODS: Here, we report
      the effectiveness of cutting and splitting of the tentorium in 3 patients with
      trigeminal neuralgia. RESULTS: The clinical results were good, the pain
      disappeared in all patients without medication, and no complications occurred.
      CONCLUSIONS: In cases of trigeminal neuralgia caused by VBD, this technique may
      be as useful as traditional microvascular decompression around the trigeminal
      nerve root entry zone.

PMID- 30098438
TI  - Stent-Assisted Coil Embolization for Ruptured Intracranial Dissecting Aneurysms
      Involving Essential Vessels.
AB  - BACKGROUND: The optimal treatment strategy for ruptured intracranial dissecting
      aneurysms involving essential vessels remains controversial. The aim of this
      study was to review the safety and efficacy of endovascular treatment at our
      center. METHODS: A total of 11 ruptured intracranial dissecting aneurysms
      involving branching arteries or arising from a major intracranial vessel without
      tolerance of parental artery occlusion were treated consecutively using
      endovascular techniques from January 2013 through December 2017. The lesions
      involved 4 internal carotid arteries, 2 basilar arteries, 3 vertebral arteries,
      and 2 posterior cerebral arteries. Clinical outcome and complications were
      evaluated retrospectively. RESULTS: Nine patients were initially treated by stent
      assisted coiling, whereas 2 underwent initial coil embolization followed by stent
      assisted coiling. Five patients required additional treatment because of
      rebleeding in 2 patients and re-expansion of the aneurysm in 3 patients. Anatomic
      preservation of parental, branching, and perforating arteries was successful in
      all patients, but thromboembolic complications related to an involved vessel
      occurred in 1 patient. After a mean follow-up period of 36 months (range, 10-63
      months), the clinical outcome was good (modified Rankin scale score 0-2) in 9
      patients, whereas 2 patients had a poor outcome (modified Rankin scale: 3 and 5)
      because of vasospasm-related delayed cerebral infarction. CONCLUSIONS: Careful
      follow-up is necessary after endovascular coiling for ruptured dissecting
      aneurysm involving essential vessels. Although additional treatment might be
      required, stent-assisted coiling could be a less invasive and feasible method for
      handling these difficult lesions.

PMID- 30098439
TI  - ACVR1 is essential for periodontium development and promotes alveolar bone
      formation.
AB  - OBJECTIVE: To explore the role of a BMP type I receptor (ACVR1) in regulating
      periodontium development, Acvr1 was conditionally disrupted in Osterix-expressing
      cells. METHODS: Mandibles from both control (Acvr1 fx/+; Osterix-Cre (+)/(-)) and
      cKO (Acvr1 fx/-; Osterix-Cre (+)/(-)) mice at postnatal day 21 (PN21) were
      scanned by micro-CT, followed by decalcification and histological observations.
      Distributions and levels of differentiation markers of fibroblasts, osteoblasts
      and cementocytes in the periodontium were detected by immunohistochemical (IHC)
      staining. RESULTS: Micro-CT results showed that bone mass and bone mineral
      density of the alveolar bones in the cKO mice were lower than those in the
      controls. Histomorphometry within the alveolar bones revealed that the lower bone
      mass observed in the cKO mice was caused by increased numbers and resorption
      activities of osteoclasts. The markers for osteoblast differentiation, Col I and
      DMP1, were reduced and the signals of the RANKL/OPG ratio were increased in the
      alveolar bones of the cKO mice compared to those of the control mice. The
      periodontal ligament in the cKO mice exhibited disorganized collagen fibers with
      weaker signals of Col I and periostin. However, there was no difference in terms
      of the cellular cementum between the two groups. CONCLUSION: ACVR1 is essential
      for normal periodontium development. ACVR1 in the osteoblasts negatively
      regulates osteoclast differentiation in association with the RANKL/OPG axis and
      thus promotes alveolar bone formation.

PMID- 30098440
TI  - Pro-angiogenic near infrared-responsive hydrogels for deliberate transgene
      expression.
AB  - : CuS nanoparticles (CuSNP) are degradable, readily prepared, inexpensive to
      produce and efficiently cleared from the body. In this work, we explored the
      feasibility of CuSNP to function as degradable near infrared (NIR)
      nanotransducers within fibrin-based cellular scaffolds. To prepare NIR-responsive
      CuSNP hydrogels, fibrinogen was dissolved in cell culture medium and supplemented
      with aqueous dispersions of CuSNP. Fibrinogen polymerization was catalyzed by the
      addition of thrombin. In some experiments, HUVEC, C3H/10T1/2 or C3H/10T1/2-fLuc
      cells, that harbor a heat-activated and rapamycin-dependent gene switch for
      regulating the expression of firefly luciferase transgene, were incorporated to
      the sol phase of the hydrogel. For in vivo experiments, hydrogels were injected
      subcutaneously in the back of adult C3H/HeN mice. Upon NIR irradiation, CuSNP
      hydrogels allowed heat-inducible and rapamycin-dependent transgene expression in
      cells contained therein, in vitro and in vivo. C3H/10T1/2 cells cultured in CuSNP
      hydrogels increased metabolic activity, survival rate and fibrinolytic activity,
      which correlated with changes at the transcriptome level. Media conditioned by
      CuSNP hydrogels increased viability of HUVEC which formed pseudocapillary
      structures and remodeled protein matrix when entrapped within these hydrogels.
      After long-term implantation, the skin patches that covered the CuSNP hydrogels
      showed increased capillary density which was not detected in mice implanted with
      matrices lacking CuSNP. In summary, NIR-responsive scaffolds harboring CuSNP
      offer compelling features in the tissue engineering field, as degradable implants
      with enhanced integration capacity in host tissues that can provide remote
      controlled deployment of therapeutic gene products. STATEMENT OF SIGNIFICANCE:
      Hydrogels composed of fibrin embedding copper sulfide nanoparticles (CuSNP)
      efficiently convert incident near infrared (NIR) energy into heat and can
      function as cellular scaffolding. NIR laser irradiation of CuSNP hydrogels can be
      employed to remotely induce spatiotemporal patterns of transgene expression in
      genetically engineered multipotent stem cells. CuSNP incorporation in hydrogel
      architecture accelerates the cell-mediated degradation of the fibrin matrix and
      induces pro-angiogenic responses that may facilitate the integration of these NIR
      responsive scaffolds in host tissues. CuSNP hydrogels that harbor cells capable
      of controlled expression of therapeutic gene products may be well suited for
      tissue engineering as they are biodegradable, enhance implant vascularization and
      can be used to deploy growth factors in a desired spatiotemporal fashion.

PMID- 30098441
TI  - Synergistic effect of dual targeting vaccine adjuvant with aminated beta-glucan
      and CpG-oligodeoxynucleotides for both humoral and cellular immune responses.
AB  - : Presently, clinically approved adjuvants (such as aluminum salts) fail to
      induce cellular immune responses, which is crucial to defend against
      intracellular pathogens (including HIV, malaria, tuberculosis and Ebola) and
      cancer. However, Freund's complete adjuvant potently stimulates both humoral and
      cellular immune responses, accompanying by high toxicity and severe side
      reactions. Here in this work, a CpG-oligodeoxynucleotides (CpG-OND) crosslinked
      aminated beta-glucan-Ovalbumin dual targeting nanoparticle (CpG-OND-AG-OVA) is
      prepared through a simple and mild ionic complexation method. The aminated beta
      glucan plays dual roles as antigen presenting cells (APCs) targeted carrier and
      immunopotentiator (targeting and activating dectin-1 on APCs). Meanwhile, CpG-OND
      also plays dual roles as ionic crosslinker and immunopotentiator (targeting and
      activating Toll-like receptor 9 in APCs). The adjuvant activity of the particles
      is evaluated through in vitro and in vivo experiments. The particles
      significantly enhance uptake and sustained proteolytic processing of antigens,
      and result in APCs maturation, inducing robust Th1 and Th2-type immune responses
      comparable to Freund's adjuvant without obvious toxicity. The potent adjuvant
      activity of the nanoparticles may originate from dual targeting synergistic
      effects between aminated beta-glucan and CpG-OND. Accordingly, the dual targeting
      nanoparticles may be a promising vaccine adjuvant for inducing robust humoral and
      cellular immune responses against infectious diseases and cancers. STATEMENT OF
      SIGNIFICANCE: An ideal adjuvant for subunit vaccine should act as both a carrier
      to enhance the uptake, sustained processing and cytosolic delivery of antigens,
      and an immunopotentiator to stimulate antigen presenting cells (APCs) for
      activation of naive T cells. Additionally, it should be easy to obtain and safe
      with negligible toxicity. Unfortunately, both synthetic and natural polymers that
      have been developed into antigen delivery system cannot completely fulfill the
      requirements. In the present study, the authors design nanoparticles with
      aminated beta-glucan and CpG-oligodeoxynucleotides (CpG-OND) through a simple and
      mild method. beta-Glucan (a dectin-1 and TLR2 targeted PAMP) and CpG-OND (a TLR9
      targeted PAMP) are readily accessible. Aminated beta-glucan plays dual roles in
      the nanoparticle as APCs targeted carrier and immunopotentiator. Meanwhile, CpG
      OND also plays dual roles as crosslinker and APCs targeted immunopotentiator. By
      making use of synergistic effect of the dual targeting vaccine adjuvant with
      aminated beta-glucan and CpG-OND, the nanoparticles induce robust antigen
      specific immune responses comparable to Freund's adjuvant without obvious
      toxicity.

PMID- 30098442
TI  - Using Mobile Health to Promote Early Language Development: A Narrative Review.
AB  - In this narrative review, we first present a brief overview of known disparities
      in children's language development based on socioeconomic status and efforts in
      the primary care setting to promote children's language development. Next, we
      define mobile health (m-health) and review the limited, published literature
      regarding the effectiveness of m-health interventions in promoting children's
      health, in general, and language development, in particular. Finally, we discuss
      the potential role of smartphone applications to increase parental behaviors that
      promote their children's language development, as well as challenges that should
      be addressed as the field of m-health continues to grow.

PMID- 30098443
TI  - Development and Assessment of an Online Training for the Medical Response to Sex
      Trafficking of Minors.

PMID- 30098444
TI  - Effects of low concentrations copper on antioxidant responses, DNA damage and
      genotoxicity in thick shell mussel Mytilus coruscus.
AB  - For the aim to study potential detrimental effects induced by Cu exposure at low,
      environmentally relevant concentrations, the in vivo activities at different
      levels of biological organisations of thick shell mussel Mytilus coruscus exposed
      to two levels of copper were assessed. Cu-induced stresses were evaluated through
      antioxidant responses, DNA damage and genotoxicity. The results revealed
      significant higher SOD and CAT activities, and MDA concentration in haemocytes of
      M. coruscus with Cu exposure at 8 MUg/L, while only significant accumulation in
      CAT activity with Cu exposure at 2 MUg/L and no significant changes with SOD
      activity and MDA concentration at this level of Cu exposure. Copper exposure
      induced DNA damage as induction of OTM value in a time- and concentration
      dependent manner. In addition, copper exposure could significantly induced the
      expressions of MT-10, Hsp70, Hsp90 and C3. The present results deepen the mussels
      as a suitable model marine invertebrate species to study potential detrimental
      effects induced by possible toxicants, in combinations at different levels of
      biological organisations.

PMID- 30098445
TI  - Analysis and identification of tyrosine phosphorylated proteins in hemocytes of
      Litopenaeus vannamei infected with WSSV.
AB  - Previous studies have demonstrated that protein tyrosine phosphorylation plays an
      important role in WSSV infection. In the present work, in order to further
      elucidate the potential role of protein tyrosine phosphorylation in white spot
      syndrome virus (WSSV) infection. The expression variation of tyrosine
      phosphorylated proteins in hemocytes of shrimp (Litopenaeus vannamei) after WSSV
      infection were examined by flow cytometric immunofluorescence assay (FCIFA) and
      enzyme linked immunosorbent assay (ELISA), and results showed that the level of
      protein tyrosine phosphorylation in hemocytes fluctuated significantly after WSSV
      infection and exhibited two peaks at 6 and 24 h post infection (hpi). Meanwhile,
      tyrosine phosphorylated proteins in hemocytes after WSSV infection were also
      detected by cell immunofluorescence, and results showed that the fluorescence
      intensity in hemocytes was altered with the course of WSSV infection and showed
      stronger fluorescent signals at 6 and 24 hpi compared to other time points.
      Furthermore, two dimensional gel electrophoresis (2-DE) and 2-DE western blotting
      were applied to identify the differentially expressed tyrosine phosphorylated
      proteins in hemocytes before and after WSSV infection. The result of 2-DE western
      blotting showed that there were nine tyrosine phosphorylated proteins in the
      hemocytes of healthy shrimp, whereas twenty-one tyrosine phosphorylated proteins
      were detected in the hemocytes of shrimp at 6hpi. Then, the differential tyrosine
      phosphorylated proteins were analyzed by Mass Spectrometry (MS), and eight of
      them were identified to be sodium/potassium-transporting ATPase subunit alpha,
      ubiquitin/ribosomal L40 fusion protein, actin-D, phosphopyruvate hydratase, beta
      actin, ATP synthase subunit beta, receptor for activated protein kinase c1 and
      protein disulfide-isomerase. Moreover, the expression levels of sodium/potassium
      transporting ATPase subunit alpha, ubiquitin/ribosomal L40 fusion protein,
      phosphopyruvate hydratase, ATP synthase subunit beta, receptor for activated
      protein kinase c1 and protein disulfide-isomerase were examined to be up
      regulated post WSSV infection by quantitative real-time RT-PCR. Taken together,
      these results demonstrated that protein tyrosine phosphorylation was involved in
      the process of WSSV infection, which might play an important role in the immune
      response to WSSV infection in shrimp.

PMID- 30098446
TI  - Influence of dietary inosine and vitamin C supplementation on growth, blood
      chemistry, oxidative stress, innate and adaptive immune responses of red sea
      bream, Pagrus major juvenile.
AB  - Both inosine (INO) and vitamin C (l-ascorbic acid, AsA) play important roles in
      growth performance, feed utilization and health status of fish. Therefore, a 56
      days feeding trial was conducted to determine the interactive effects of dietary
      INO and AsA on growth performance, oxidative status, innate and adaptive immune
      responses of red sea bream. Fish growth performance and fed utilization
      parameters were significantly affected by dietary INO supplementation but not by
      AsA. Fish fed diets with INO at 4 g kg-1 diet in combination of high and low
      levels of AsA (3.1 g kg-1 and 9.3 g kg-1) produced the highest growth and feed
      utilization performances. In terms of growth and feed utilization performances no
      significant interaction effects were observed between INO and AsA. Dietary INO
      significantly influenced hematocrit, glucose and glutamyl oxaloacetic
      transaminase (GOT) content of red sea bream meanwhile AsA also significantly
      influenced hematocrit, glucose, total cholesterol, blood urea nitrogen (BUN) and
      glutamic-pyruvate transaminase (GPT) content of the test fish. No significant
      interaction effects was also observed between INO and AsA on measured
      hematological parameters. Reactive oxygen metabolites (d-ROMs) significantly
      influenced by both INO and AsA. Fish fed diet groups D1, D4 and D6 showed best
      oxidative stress resistance. Only INO was a significant factor on nitro-blue
      tetrazolium activity (NBT) and bactericidal activity (BA). Neither INO nor AsA
      was a significant factor on serum catalase activity (CAT), total serum protein
      (TSP), peroxidase activity (PA) and lysozyme activity (LA). No significant
      interaction effects was observed between INO and AsA on measured innate immune
      parameters. Agglutination antibody titer was significantly influenced by dietary
      supplementation, after 15 days of vaccination but not in 21 days. In the day 15th
      fish and diet group D3 and D5 showed significantly higher values compared to diet
      groups control and D1. INO was the only significant factor of increasing
      agglutination antibody titer in 15 t h day. While AsA was not a significant
      factor on agglutination antibody titer values in day 15 t h, there was an
      interaction between dietary INO and AsA levels. Finally under the experimental
      conditions, fish fed high INO and low AsA levels (4 g kg-1 and 0.31 g kg-1 diet,
      respectively) showed best growth and feed utilization performance.
      Simultaneously, low level of INO and high level of AsA (2 g kg-1 and 0.93 g kg-1
      diet, respectively) improved blood chemistry and immunological parameters.
      Furthermore, combined use of INO and AsA is possible to improve hemato
      immunological responses of red sea bream.

PMID- 30098447
TI  - Functional and morphologic outcomes of CAD/CAM-assisted versus conventional
      microvascular fibular free flap reconstruction of the mandible: A retrospective
      study of 25 cases.
AB  - INTRODUCTION: Mandibular reconstruction using fibula free flap has been improved
      in the last decade with computer-aided design and computer-aided manufacturing
      (CAD/CAM) but any functional and aesthetic evaluation of their reattempts has
      been realized. Aim of this retrospective study is to compare functional and
      morphologic outcomes after mandibular reconstruction with fibula free flap using
      CAD/CAM or conventional peroperative shaping for mandible reconstruction.
      Moreover, we compared quality of life, patient and surgery characteristics in the
      two groups. PATIENTS AND METHODS: We realized a monocentric retrospective
      analyzed of 25 cases of unilateral mandibular reconstruction divided in two
      groups, using CAD/CAM (12 patient) or conventional approach (13 patients) between
      April 2012 and March. Functional and aesthetic measurements were performed
      postoperatively. RESULTS: Mouth opening, laterotrusion and protrusion of the
      mandible seemed to be improved in CAD/CAM group compared with conventional group
      but did not differ significantly. Quality of life, bite force, masticatory
      ability, eating and chewing satisfaction, appearance and social activity
      satisfaction did not differ significantly in the two groups. CONCLUSION: Even if
      no superiority has been established for CAD/CAM group regarding functional and
      aesthetic outcomes, a prospective design of future studies and transdisciplinary
      approach should improve our data and their interpretations. Thus, the integration
      of virtual planning and guided surgery is definitely of significant value and
      must be considered in complex maxillofacial reconstructions.

PMID- 30098448
TI  - Two step reconstruction of traumatic ear skin avulsion using Integra graft.
AB  - Treatment of traumatic ear injuries have always been a challenge. Preservation of
      the auricular cartilage is key for reconstruction. Many techniques have been
      reported for the management of exposed ear perichondrium. We present patient who
      sustained right ear soft tissue avulsion. Initial examination the patient
      revealed skin avulsion with exposed cartilage from the concha, scapha and
      antihelix on the right ear. The treatment sequence included debridement and
      application of Integra graft. This was followed by dressing changes every three
      days and three weeks. Once adequate vascularization was noted a split thickness
      skin graft was used for final reconstruction. Integra has been widely used for
      the management of burns as well as exposed bone and cartilage. However, its use
      in traumatic ear injuries has not been reported. This technique allowed for the
      reconstruction of a large skin avulsion from the right ear with minimal donor
      site morbidity and avoidance of local rotational flaps that could hinder later
      reconstructions if needed.

PMID- 30098449
TI  - Admission cardiotocography: A hospital based validation study.
AB  - OBJECTIVE: Admission CTG is a short fetal heart rate (FHR) tracing recorded
      immediately at hospital admission to avoid unnecessary delay in action among
      pregnancies complicated by pre-existent fetal distress. There are different
      opinions regarding the value of the admission CTG, especially in low risk
      pregnancies. STUDY DESIGN: A retrospective validation study from Karolinska
      University Hospital, Jan 2011 to June 2015 (total number of deliveries = 40,061).
      All women who underwent emergency cesarean section within one hour of admittance
      due to suspected fetal distress were identified. We assessed whether an admission
      CTG was performed, if it was beneficial for the decision to perform emergent
      cesarean delivery and if there were objective signs of fetal compromise or if it
      was performed unnecessarily. The main outcome was the benefit of the admission
      CTG in the decision to perform emergency cesarean delivery. RESULTS: Eighty-eight
      cases (0.22%) fulfilled our inclusion criteria. Over 90% of these women (80/88)
      had objective evidence of compromised fetal well-being, i.e., indicating that
      emergent delivery was necessary. In 74% (54/73) of all cases was admission CTG
      determined to have been beneficial in the decision to perform cesarean delivery,
      equally effective of those classified as low- and high risk pregnancies before
      admission. In 28% (15/54) the CTG pathology was deemed difficult to identify by
      auscultation. CONCLUSION: Admission CTG was deemed beneficial in 74% of both low-
      and high-risk pregnancies that were delivered by emergent cesarean section within
      one hour of admittance due to suspected fetal distress.

PMID- 30098450
TI  - Virome of > 12 thousand Culex mosquitoes from throughout California.
AB  - Metagenomic analysis of whole mosquitoes allows the genetic characterization of
      all associated viruses, including arboviruses and insect-specific viruses, plus
      those in their diet or infecting their parasites. We describe here the virome in
      mosquitoes, primarily Culex pipiens complex, Cx. tarsalis and Cx. erythrothorax,
      collected in 2016 from 31 counties in California, USA. The nearly complete
      genomes of 56 viruses, including 32 novel genomes, some from potentially novel
      RNA and DNA viral families or genera, were assembled and phylogenetically
      analyzed, significantly expanding the known Culex-associated virome. The majority
      of detected viral sequences originated from single-stranded RNA viral families
      with members known to infect insects, plants, or from unknown hosts. These
      reference viral genomes will facilitate the identification of related viruses in
      other insect species and to monitor changes in the virome of Culex mosquito
      populations to define factors influencing their transmission and possible impact
      on their insect hosts.

PMID- 30098451
TI  - Illicit drug use and work in a model therapeutic workplace.
AB  - BACKGROUND: The link between illicit drug use and impaired employee performance
      in the workplace has been assumed, but the relation has not been demonstrated
      clearly in research. This study was an evaluation of the relations between
      cocaine and opiate use, attendance, and performance in a job skills training
      program in a population with high rates of drug use. METHODS: Out-of-treatment
      injection drug users (N = 42) attended a model therapeutic workplace where they
      could earn a maximum pay of around $10 per hour, 4 h every weekday, for 30 weeks.
      At the workplace, participants could complete practice trials on computer-based
      typing and keypad training programs. Participants were asked to provide urine
      samples thrice weekly, which were tested for opiates and cocaine. RESULTS:
      Participants worked for more hours on a program that resulted in a flat hourly
      wage when their urine was negative for opiates and cocaine than when their urine
      was opiate and cocaine positive. Attendance was positively associated with opiate
      negative samples during the study. When participants attended the workplace,
      however, their performance was not related to drug use. Participants completed
      the same number of practice trials, performed at the same accuracy, and typed at
      the same speed when they were positive and negative for cocaine and opiates.
      CONCLUSIONS: Contrary to common expectations, this study failed to show that the
      use of opiates or cocaine affected in-training performance, even though opiate
      and cocaine use predicted reduced attendance under some circumstances.

PMID- 30098452
TI  - Automatic recognition of arrhythmia based on principal component analysis network
      and linear support vector machine.
AB  - Electrocardiogram (ECG) classification is an important process in identifying
      arrhythmia, and neural network models have been widely used in this field.
      However, these models are often disrupted by heartbeat noise and are negatively
      affected by skewed data. To address these problems, a novel heartbeat recognition
      method is presented. The aim of this study is to apply a principal component
      analysis network (PCANet) for feature extraction based on a noisy ECG signal. To
      improve the classification speed, a linear support vector machine (SVM) was
      applied. In our experiments, we identified five types of imbalanced original and
      noise-free ECGs in the MIT-BIH arrhythmia database to verify the effectiveness of
      our algorithm and achieved 97.77% and 97.08% accuracy, respectively. The results
      show that our method has high recognition accuracy in the classification of
      skewed and noisy heartbeats, indicating that our method is a practical ECG
      recognition method with suitable noise robustness and skewed data applicability.

PMID- 30098453
TI  - Do learners with special education needs really feel included? Evidence from the
      Perception of Inclusion Questionnaire and Strengths and Difficulties
      Questionnaire.
AB  - BACKGROUND: School inclusion is an important right of students in school systems
      around the world. However, many students with special education needs (SEN) have
      lower perceptions of inclusion despite attending inclusive schools. AIMS: This
      study examined perceived levels of inclusion, academic self-concept and
      developmental problems in inclusive schools. METHODS AND PROCEDURES: The
      Strengths and Difficulties Questionnaire and the Perception of Inclusion
      Questionnaire were administered at two measurement points (6th and 7th grade; n =
      407, including 48 with SEN) at multiple inclusive schools. Responses were
      compared based on gender, grade level, and SEN. Factor structure and measurement
      invariance were evaluated. OUTCOMES AND RESULTS: Factor structures of both
      questionnaires were confirmed. Academic self-concept and emotional inclusion were
      lower for learners with SEN. However, these effects shrank in grade 7. Similarly,
      academic self-concept increased between grade 6 and 7. Lastly, learners with SEN
      had a higher level of conduct problems. CONCLUSIONS AND IMPLICATIONS: Both
      instruments remain suitable for use in comparisons in inclusive schools.
      Significant differences exist for learners with SEN in inclusive classrooms,
      although these differences may shrink over time. We recommend the continued use
      of the Perception of Inclusion Questionnaire for information about school
      inclusion and for learners with SEN.

PMID- 30098454
TI  - Modified ride-on cars and mastery motivation in young children with disabilities:
      Effects of environmental modifications.
AB  - BACKGROUND: Independent mobility is important for children's psychological
      development. Modified ride-on cars are innovative, alternative options to enhance
      independent mobility, socialization, and motivation in young children with
      disabilities. AIM: We compared the effects of combining ride-on car use and a
      social interaction training program on mastery motivation and home affordances
      with a home education program in young children with disabilities. METHODS AND
      PROCEDURES: Twenty-nine children with disabilities aged 1-3 years were recruited.
      The treatment group (n = 15) received two 2-h sessions/week for 9 weeks of ride
      on car training in a hospital environment in Taiwan. The control group (n = 14)
      underwent similar home education programs. No treatment except regular therapy
      was administered during the 9-week follow-up period. Assessments included the
      Revised Dimensions of Mastery Questionnaire-Chinese version and the Affordance in
      the Home Environment for Motor Development-Toddler version-Chinese version.
      OUTCOMES AND RESULTS: The treatment group (compared to controls) had
      significantly greater improvements in object persistence during the intervention.
      Both groups showed significant improvements in mastery pleasure and home
      affordances during the intervention. CONCLUSIONS AND IMPLICATIONS: This novel
      study showed the potential use of modified ride-on cars to enhance mastery
      motivation in a hospital environment.

PMID- 30098455
TI  - Bivariate extreme value modeling for road safety estimation.
AB  - Surrogate safety measures have been advocated as a complementary approach to
      study safety from a broader perspective than relying on crash data alone. This
      study proposes an approach to incorporate different surrogate safety measures in
      a unified framework for road safety estimation within the bivariate extreme value
      theory framework. The model structure, model specification, threshold selection
      method, and parameter estimation method of the bivariate threshold excess model
      are introduced. Two surrogate safety measures, post encroachment time (PET) and
      length proportion of merging (LPM), are chosen to characterize the severity of
      merging events on freeway entrance merging areas. Based on the field data
      collected along Highway 417 in the City of Ottawa, Ontario, Canada, the bivariate
      modelling methods with seven distribution functions are applied and compared, and
      the model with logistic distribution function is selected as the best model. The
      best bivariate models' estimation results are then evaluated by comparing them to
      their two marginal (univariate Generalized Pareto distribution) models. The
      results show that the bivariate models tend to generate crash estimates that are
      much closer to observed crashes than univariate models. A more important finding
      is that incorporating two surrogate safety measures into the bivariate models can
      significantly reduce the uncertainty of crash estimates. The efficiency of a
      bivariate model is not evidently better than either of its marginal models, but
      it is expected to be improved with data of a prolonged observation period. This
      study is also a step forward in the direction of developing multivariate safety
      hierarchy models, since models of the safety hierarchy have been predominantly
      univariate.

PMID- 30098456
TI  - alpha-Tocopherol transfer protein does not regulate the cellular uptake and
      intracellular distribution of alpha- and gamma-tocopherols and -tocotrienols in
      cultured liver cells.
AB  - Liver cells express a cytosolic alpha-tocopherol transfer protein (alphaTTP) with
      high binding affinity for alpha-tocopherol (alphaT) and much lower affinities for
      the non-alphaT congeners. The role of alphaTTP in the intracellular distribution
      of the different vitamin E forms is currently unknown. We therefore investigated
      the intracellular localization of alphaT, gamma-tocopherol (gammaT), alpha
      tocotrienol (alphaT3), and gamma-tocotrienol (gammaT3) in cultured hepatic cells
      with and without stable expression of alphaTTP. We first determined cellular
      uptake of the four congeners and found the methylation of the chromanol ring and
      saturation of the sidechain to be important factors, with tocotrienols being
      taken up more efficiently than tocopherols and the gamma-congeners more than the
      alpha-congeners, irrespective of the expression of alphaTTP. This, however, could
      perhaps also be due to an observed higher stability of tocotrienols, compared to
      tocopherols, in culture media rather than a higher absorption. We then incubated
      HepG2 cells and alphaTTP-expressing HepG2 cells with alphaT, gammaT, alphaT3, or
      gammaT3, isolated organelle fractions by density gradient centrifugation, and
      determined the concentrations of the congeners in the subcellular fractions. All
      four congeners were primarily associated with the lysosomes, endoplasmic
      reticulum, and plasma membrane, whereas only alphaT correlated with mitochondria.
      Neither the chromanol ring methylation or sidechain saturation, nor the
      expression of alphaTTP were important factors for the intracellular distribution
      of vitamin E. In conclusion, alphaTTP does not appear to regulate the uptake and
      intracellular localization of different vitamin E congeners in cultured liver
      cells.

PMID- 30098457
TI  - Redox regulation of GRPEL2 nucleotide exchange factor for mitochondrial HSP70
      chaperone.
AB  - Mitochondria are central organelles to cellular metabolism. Their function relies
      largely on nuclear-encoded proteins that must be imported from the cytosol, and
      thus the protein import pathways are important for the maintenance of
      mitochondrial proteostasis. Mitochondrial HSP70 (mtHsp70) is a key component in
      facilitating the translocation of proteins through the inner membrane into the
      mitochondrial matrix. Its protein folding cycle is regulated by the nucleotide
      exchange factor GrpE, which triggers the release of folded proteins by ATP
      rebinding. Vertebrates have two mitochondrial GrpE paralogs, GRPEL1 and 2, but
      without clearly defined roles. Using BioID proximity labeling to identify
      potential binding partners of the GRPELs in the mitochondrial matrix, we obtained
      results supporting a model where both GRPELs regulate mtHsp70 as homodimers. We
      show that GRPEL2 is not essential in human cultured cells, and its absence does
      not prevent mitochondrial protein import. Instead we find that GRPEL2 is redox
      regulated in oxidative stress. In the presence of hydrogen peroxide, GRPEL2 forms
      dimers through intermolecular disulfide bonds in which Cys87 is the thiol switch.
      We propose that the dimerization of GRPEL2 may activate the folding machinery
      responsible for protein import into mitochondrial matrix or enhance the chaperone
      activity of mtHSP70, thus protecting mitochondrial proteostasis in oxidative
      stress.

PMID- 30098459
TI  - Swapping the roles of bacteriocins and bacteriophages in food biotechnology.
AB  - To move towards a safer and more sustainable food production chain, natural
      antimicrobials have been traditionally applied to enhance safety. This is well
      exemplified by the use of bacteriocins, antimicrobial peptides synthesized by
      bacteria, as food biopreservatives. However, as knowledge on bacteriocin biology
      develops, novel functions beyond food preservation emerge and a shift towards
      health applications is positioning bacteriocins as anti-infectives and modulators
      of gut microbiota. On the other hand, bacteriophages, viruses infecting bacteria,
      have been long regarded as a threat for dairy fermentations. However, they may
      also become allies when specific phages infecting pathogenic or spoilage bacteria
      are intentionally used. This review summarizes the 'dark side' and rather
      unexplored roles of bacteriocins and phages that, certainly, have much to learn
      from each other.

PMID- 30098458
TI  - The effect of tyramine infusion and exercise on blood flow, coagulation and clot
      microstructure in healthy individuals.
AB  - BACKGROUND: The long term benefits of exercise on the cardiovascular status of a
      patient have been proven, however, their benefit/risk relationship with exercise
      intensity is unclear. Furthermore, many thromboembolic diseases such as
      myocardial infarction and ischaemic stroke are associated with profound
      catecholamine release. In this study we explore the relationship between
      catecholamine release and hemodynamic changes and their effect on coagulation.
      MATERIALS AND METHODS: Twelve healthy recreationally active males were recruited.
      Local anesthesia was given and catheters were placed under aseptic conditions, in
      the femoral artery and vein of the experimental leg. The first experiment
      involved tyramine infusion into the femoral artery at a dose of 1.0 MUmol.min-1.L
      leg volume-1. The second experiment involved single leg knee-extensor exercise
      performed at 30 W for 15 min. Venous blood was collected at each time point to
      assess clot microstructure using the df biomarker. RESULTS AND CONCLUSIONS:
      Tyramine infusion causes a local noradrenaline release in the leg. The increase
      in noradrenaline was associated with a significant increase in clot
      microstructure formation (df increased from 1.692 +/- 0.029 to 1.722 +/- 0.047, p
      = 0.016). Additionally moderate intensity single leg knee extensor exercise,
      which minimally alters sympathetic activity, also induced an increases in df
      (from 1.688 +/- 0.025 to 1.723 +/- 0.023, p = 0.001). This suggests that exercise
      can alter clot microstructure formation both via an increase in catecholeamine
      levels and by factors related to muscle activity per se, such as increased blood
      flow and consequent shear. These findings have implications for recommendations
      of exercise in patients at risk of cardiovascular events.

PMID- 30098460
TI  - Following anticancer drug activity in cell lysates with DNA devices.
AB  - There is a great need to track the selectivity of anticancer drug activity and to
      understand the mechanisms of associated biological activity. Here we focus our
      studies on the specific NQO1 bioactivatable drug, beta-lapachone, which is in
      several Phase I clinical trials to treat human non-small cell lung, pancreatic
      and breast cancers. Multi-electrode chips with electrochemically-active DNA
      monolayers are used to track anticancer drug activity in cellular lysates and
      correlate cell death activity with DNA damage. Cells were prepared from the
      triple-negative breast cancer (TNBC) cell line, MDA-MB-231 (231) to be proficient
      or deficient in expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) enzyme,
      which is overexpressed in most solid cancers and lacking in control healthy
      cells. Cells were lysed and added to chips, and the impact of beta-lapachone
      (beta-lap), an NQO1-dependent DNA-damaging drug, was tracked with DNA
      electrochemical signal changes arising from drug-induced DNA damage.
      Electrochemical DNA devices showed a 3.7-fold difference in the electrochemical
      responses in NQO1+ over NQO1- cell lysates, as well as 10-20-fold selectivity to
      catalase and dicoumarol controls that deactivate DNA damaging pathways.
      Concentration-dependence studies revealed that 1.4 uM beta-lap correlated with
      the onset of cell death from viability assays and the midpoint of DNA damage on
      the chip, and 2.5 uM beta-lap correlated with the midpoint of cell death and the
      saturation of DNA damage on the chip. Results indicate that these devices could
      inform therapeutic decisions for cancer treatment.

PMID- 30098461
TI  - Au nanoparticles functionalized 3D-MoS2 nanoflower: An efficient SERS matrix for
      biomolecule sensing.
AB  - Fabrication of Molybdenum disulfide (MoS2) nanostructures and surface
      functionalization with noble metal nano particles is an emerging field of
      research as it has potential applications in electronic devices and chemical
      sensing. Here we report application of gold nanoparticles (AuNPs) decorated MoS2
      nanoflowers (Au-MoS2 NFs) as an efficient bio-sensor. MoS2 NFs, synthesized using
      green synthesis process, are further functionalized with AuNPs to tune their
      physical properties and make them more appropriate for biological applications.
      The abundant 'hot-spots' created by AuNPs through localization of electromagnetic
      field endows the Au-MoS2 hybrid structure as an excellent substrate for
      biochemical sensing through surface enhanced Raman scattering (SERS). The sensing
      efficiency of the SERS substrate is examined using Rh6G as probe molecule with
      concentration as low as 10-12 M. Main emphasis is given in detecting free
      bilirubin, an important component of human blood, using SERS technique. Au-MoS2
      NF SERS substrate exhibits high sensitivity, stability and excellent
      reproducibility in sensing bilirubin from high level (10-3 M) to picomolar level.
      The concentration (C) dependent SERS intensity (I) is found to follow the general
      relationship I = Calpha, with alpha ranging from 0.09 to 0.12. The substrate
      shows excellent selectivity and reliability while sensing of free bilirubin
      performed in human serum in the presence of crucial interferences such as
      dextrose, cholesterol and phosphate. In the present study, this Au-MoS2 hybrid
      offers a new potential biosensing technology for free bilirubin detection and is
      anticipated to be applied for clinic diagnosis.

PMID- 30098462
TI  - Trypsin electrochemical sensing using two-dimensional molecularly imprinted
      polymers on 96-well microplates.
AB  - Molecular imprinting is an efficient technology to create artificial receptors
      with antibody-like binding properties for a variety of applications such as
      separation and sensing. In this work, a new sensing method was introduced by
      combining a two-dimensional molecularly imprinted polymer (2D-MIP) film  with
      copper oxide nanoparticles (CuO NPs) labeling for signal conversion and
      amplification. CuO labeling can effectively monitor the thickness of 2D-MIPs to
      achieve the best imprinting effect. Trypsin imprinted polymer based
      electrochemical sensor on 96-well microplates was constructed and a good dynamic
      response was observed in the range of 0.5-500  ng/mL. Furthermore, detections of
      trypsin in fetal bovine serum were demonstrated using the imprinted polymer thin
      films. Our electrochemical sensors possess an excellent specificity, fast
      kinetics, high sensitivity and low cost, which have great potential in biological
      analysis.

PMID- 30098463
TI  - Aptasensor designed via the stochastic tunneling-basin hopping method for
      biosensing of vascular endothelial growth factor.
AB  - The Systematic Evolution Ligands by Exponential Enrichment (SELEX) is common used
      for selection of high affinity single-stranded DNA (ssDNA) aptamer with target
      protein. However, we do not know what the most stable configuration of the
      selected aptamer bound with target protein is. Therefore, a systematic search
      process using the stochastic tunneling-basin hopping (STUN-BH) method is proposed
      to find the most stable configuration of the ssDNA aptamer specific for vascular
      endothelial growth factor (VEGF) capture (AptVEGF; 5'-TGTGGGGGTGGACGGGCCGGGTAGA
      3'). After the most stable configuration was obtained by the STUN-BH method,
      molecular dynamics (MD) simulation was carried out to investigate the thermal
      stability of AptVEGF/VEGF at 300 K in both vacuum and water. All molecular
      simulations were conducted with the large-scale atomic/molecular massively
      parallel simulator (LAMMPS), and the AMBER99SB force field was used to describe
      the atomic interactions for the current AptVEGF/VEGF system. The three most
      stable AptVEGF/VEGF configurations obtained by the STUN-BH method indicated that
      AptVEGF residues exhibit greater affinity for VEGF surface loop fragments as
      compared with surface alpha helix and beta sheet fragments. Results indicated
      that after the first AptVEGF (AptVEGF I) occupies most of the VEGF loop fragment,
      the second AptVEGF (AptVEGF II) is adsorbed by the rest of the VEGF loop fragment
      and the VEGF Chain B beta sheet fragment, resulting in a 24.8% reduction in
      binding strength as compared to that of AptVEGF I. Furthermore, when AptVEGF I
      and AptVEGF II chains were stably adsorbed by VEGF, the third AptVEGF (AptVEGF
      III) chain can only partially attach to VEGF, as confirmed by real AptVEGF-VEGF
      binding experiments. Lastly, we demonstrated that the aptasensor constructed
      according to MD simulation is highly sensitive for VEGF with a linear detection
      range of 10 pg/mL-10 ng/mL.

PMID- 30098464
TI  - A self-powered photoelectrochemical glucose biosensor based on supercapacitor
      Co3O4-CNT hybrid on TiO2.
AB  - In this study, a photoelectrochemical (PEC) biosensor was constructed by
      depositing supercapacitor carbon nanotubes (CNT) and Co3O4 onto the anatase TiO2
      coated ITO electrodes. Herein, supercapacitor Co3O4 was employed as a
      semiconductor with a band gap of ~2.07 eV, and the supercapacitor behavior of the
      PEC system was improved by introducing CNT into the electrode material.
      Furthermore, a self-empowering glucose biosensor operating at 0 V was constructed
      for the first time. Also, upon the formation of p-n junction, Co3O4 was rendered
      electron accepting material, unlike its usual use in photocatalytic systems.
      Co3O4-CNT-anatase TiO2 semiconductor hybrid was used to reduce recombination of
      exited electrons, and increasing the visible light absorption. Prior to enzyme
      immobilization, CNT containing electrode material was modified with 1-pyrene
      boronic acid via pi-pi interactions. The enzyme immobilization was carried out
      through covalent esterification between the boronic acid moiety and the
      carbohydrate part of GOx. Enzyme immobilization way enabled the close contact
      between FAD and electrode material, and the electron donor FADH2 forming after
      the enzymatic reaction can give electrons to the photogenerated holes of Co3O4
      through CNT along with H2O2 by enhancing the photocurrent. The obtained PEC
      biosensor demonstrated acceptable reproducibility and decent stability with a
      linear measurement range of 0-4 mM, a sensitivity of 0.3 uA mM-1 cm-2, and lower
      detection limit of 0.16 uM. Thus, a self-powered biosensor was constructed by
      combining the PEC, and supercapacitor behavior of Co3O4 for the first time, and
      the utilization of the present PEC material can be extended to the other analytes
      detection through photoelectrochemistry. The supercapacitor materials led to the
      high current at direct electron transfer potential range, and this phenomenon
      implies that the PEC electrode can also be used in biofuel cells to obtain high
      power.

PMID- 30098465
TI  - Peptide-templated multifunctional nanoprobe for feasible electrochemical assay of
      intracellular kinase.
AB  - Protein kinases play a critical role in regulation of intracellular signal
      transduction, whose aberrant expression is closely associated with various
      dangerous human diseases. In this paper, we propose a feasible electrochemical
      assay of intracellular kinase by incorporating peptide nanoprobe-assisted signal
      labeling and signal amplification. Protein kinase A (PKA)-specific peptide P1 is
      self-assembled on the surface of a gold electrode, serine of which could be
      phosphorylated with catalysis of PKA in the presence of adenosine-5'-triphosphate
      (ATP). Another artificial peptide P2 contains a short template for preparation of
      copper nanoparticles-based nanoprobe (P2-CuNPs) and provides arginine residues
      for specific recognition of phosphorylation site. After PKA-catalyzed
      phosphorylation, phosphorylated P1 specially binds with P2-CuNPs through ultra
      stable phosphate-guanidine interaction, and thus results in amplified
      electrochemical response from surface-attached CuNPs. Our method demonstrates a
      satisfactory sensitivity toward PKA detection with a detection limit of 0.0019
      U/mL, which is also successfully applied in intracellular PKA assay and
      inhibitory study with high specificity comparable to ELISA. Therefore, the facile
      method suggests a promising potential use in kinase-related biochemical
      fundamental research, disease diagnosis and drug discovery in the future.

PMID- 30098466
TI  - CMOS-compatible biosensor for L-carnitine detection.
AB  - A CMOS-compatible ISFET with a Ta2O5 sensitive surface was developed. The
      structure was optimized for achieving high sensitivity using a subthreshold
      operation mode and by reducing the influence of the capacitances on the value of
      subthreshold swing. The developed ISFET was used as a basis for a biosensor for L
      carnitine detection. To this end, carnitine acetyltransferase was immobilized on
      the ISFET sensitive surface. The immobilized enzyme was active (0.082 U/g model
      plate). The complete microsystem, consisting of a packaged chip, an immobilized
      enzyme and a microfluidic channel, detected L-carnitine at a range of 0.2-100 MUM
      with a LOD of 0.2 MUM. The biosensor response was linear in the range of 0.2-50
      MUM of L-carnitine with sensitivity 18.0 +/- 1.7 mV/MUM. An experiment with
      artificial urine containing 1.3 MUM L-carnitine showed that the proposed
      biosensor could be used on a real sample. Therefore, a new sensor specially
      optimized for biosensing CMOS-compatible ISFET structures and direct
      determination of L-carnitine with immobilized carnitine acetyltransferase was
      developed.

PMID- 30098467
TI  - Smartphone-based integrated voltammetry system for simultaneous detection of
      ascorbic acid, dopamine, and uric acid with graphene and gold nanoparticles
      modified screen-printed electrodes.
AB  - Ascorbic acid, dopamine, and uric acid are important electroactive biomolecules
      for health monitoring and they coexist in serum or urine. Their quantitative
      determination by electrochemistry could provide the accurate reference for
      diseases diagnosis and treatment. However, the traditional electrochemical
      workstations are too large for on-field inspection. Hence, the design of handheld
      electrochemical system for the detection of biomolecules is significant for point
      of-care testing (POCT). In this paper, a smartphone-based integrated voltammetry
      system using modified electrode was developed for simultaneous detection of
      biomolecules. The system contained a disposable sensor, a coin-size detector, and
      a smartphone equipped with application program. Screen-printed electrodes were
      used as sensors for the detection, on which reduced graphene oxide and gold
      nanoparticles were electrochemically deposited by the system. The detector was
      used with voltammetric methods, in which excitation voltage was applied on the
      sensors and subsequent current responses were detected. The smartphone is the
      core component to communicate with the detector, calculate data, and plot
      voltammograms in real-time. Then, the system was applied to detect standard
      solutions of the biomolecules and their mixtures as examples. The results showed
      that the peak currents of each substance increased with higher concentration and
      the method allowed the discrimination of the different potentials of the studied
      species. Finally, the practical applications of the system were tested through
      detections of the biomolecules in artificial urine. The results exhibited that
      the system could be used to detect electrochemical activity of biomolecules with
      linear, high sensitivity, and specific responses in point-of-care testing.

PMID- 30098468
TI  - Associations of neighborhood socioeconomic, natural and built environmental
      characteristics with a 13-year trajectory of non-work physical activity among
      civil servants in Rio de Janeiro, Brazil: The Pro-Saude Study.
AB  - Positive influences of natural and built environment characteristics on human
      physical activity have been observed mainly in high-income countries, but mixed
      results exist. We explored these relationships in Rio de Janeiro, Brazil, where
      exuberant nature coexists with high levels of social inequality and urban
      violence. Data originated from questionnaires self-administered by 1731 civil
      servants at university campuses who participated in 4 waves (1999, 2001, 2007,
      2012) of a longitudinal study, and had their residential addresses geocoded. In
      multinomial regression models, adjusted for individual sociodemographic
      characteristics, mutually adjusted associations were estimated between 13-year
      trajectories of non-work physical activity and 8 contextual variables: distances
      from waterfronts, cycle paths, outdoor gym equipment, and squares; 2 indicators
      of exposure to greenness (a vegetation index - NDVI - derived from satellite
      images, and trees close to home); an indicator of walkability (street density),
      and neighborhood average income. Compared to participants living in the upper
      quartile of distance to waterfronts, those living in its lowest quartile had 2.6
      fold higher odds (aOR: 2.62, 95% CI: 1.37-5.01) of reporting non-work PA in all 4
      study waves. Similar results were observed in relation to distance to cycle
      paths; no independent associations were observed with other natural and built
      environment variables.

PMID- 30098469
TI  - Creative, strengths-based approaches to knowledge translation within indigenous
      health research.
AB  - OBJECTIVES: Good knowledge translation efforts can lead to significant changes in
      health status and service delivery. Although there is growing literature around
      ways to conduct knowledge translation within policy and health service delivery
      sectors, literature around how to conduct dissemination within indigenous
      community-based contexts remains scant. STUDY DESIGN: Using creative, strengths
      based approaches to not only return results but also to function as tools to
      address gaps in health knowledge as identified by participants and community
      members within intergenerational contexts was a central component applied to
      dissemination and knowledge translation. METHODS: We developed a series of seven
      key considerations that we applied to the creation of dissemination products from
      qualitative interviews and focus group discussions from two Manitoba, Canada
      specific public health research projects with indigenous communities. RESULTS:
      Products created (activity sheets, board game, and non-fiction storybooks)
      considered principles of timeliness, literacy level, feasibility of reproduction,
      and meeting the stated needs of study participants. CONCLUSIONS: By creating
      products that seek not only to return study information but also to answer
      questions and address specific challenges identified by participants, it is
      possible to continue to engage in research that is meaningful and ethical and
      strengthens relationships with all stakeholders.

PMID- 30098470
TI  - The prevalence of sufficient physical activity among primary and high school
      students in Mainland China: a systematic review and meta-analysis.
AB  - OBJECTIVES: This study aims to estimate the prevalence of sufficient physical
      activity (PA) for primary and high school students in China. STUDY DESIGN: This
      is a meta-analysis study. METHODS: The literature search was carried out using
      both English and Chinese online databases, including articles published from
      January 2005 to May 2018. Statistical analyses were performed with STATA 13.0.
      RESULTS: Of 1439 articles initially retrieved, 18 studies met the inclusion
      criteria. The prevalence of sufficient PA among Chinese students varied from
      8.96% to 56.02%. With meta-analysis, the sufficient PA prevalence was 31.1%
      (27.1%-35.2%). Boys were more likely to achieve sufficient PA compared to girls
      (boys vs girls: 42.4% vs 31.5%, P < 0.001), while urban students engaged in more
      sufficient PA than their rural counterparts (urban vs rural: 42.7% vs 38.5%, P <
      0.001). Primary school students spent more time in overall PA than junior
      (primary vs junior: 45.4% vs 40.6%, P < 0.001) or senior high school students
      (primary vs senior: 45.4% vs 27.9%, P < 0.001). Students tended to be more
      physically active on weekdays than weekends (weekdays vs weekend: 57.2% vs 45.2%,
      P < 0.001). CONCLUSIONS: The prevalence of sufficient PA was 31% among Chinese
      students. Intervention campaigns are needed for promoting PA level among students
      in China.

PMID- 30098471
TI  - The latent structure of spatial skill: A test of the 2 * 2 typology.
AB  - Multiple frameworks for categorizing spatial abilities exist but it has been
      difficult to verify them using exploratory factor analysis. The present study
      tested one of these frameworks-a 2 * 2 classification scheme that crossed the
      dimensions of static/dynamic and intrinsic/extrinsic (Uttal et al., 2013)-using
      confirmatory factor analysis with data on spatial performance from kindergarten
      (N = 251), third grade (N = 246) and sixth grade students (N = 241). For
      kindergarten and third grade students, four models were tested at each grade
      level: A 1-factor model, two 2-factor models (one static vs. dynamic, the other
      intrinsic vs. extrinsic), and a 4-factor model. In sixth grade, only the 2- and 1
      factor models could be tested given the available data. Evidence that the 4
      factor model was the best fit would have validated the 2x2 model. However, the 4
      factor models failed to converge in kindergarten and third grade. Both the 1- and
      2-factor models converged in these age groups, and chi-square tests demonstrated
      that the 2-factor intrinsic-extrinsic model was the best fit at both grade
      levels. In sixth grade, only one of the 2-factor models converged and it did not
      fit significantly better than the 1-factor model. Thus, there was limited
      validation of the model in these grades, as well as a trend toward less
      dimensionality in spatial skill over development.

PMID- 30098472
TI  - Influence of inter-domain dynamics and surrounding environment flexibility on the
      direct electrochemistry and electrocatalysis of self-sufficient cytochrome P450
      3A4-BMR chimeras.
AB  - The linker region of multi-domain enzymes has a very important role for the
      interconnection of different enzyme modules and for the efficiency of catalytic
      activity. This is particularly evident for artificial chimeric systems. We
      characterised an artificial self-sufficient enzyme developed by genetic fusion of
      the catalytic domain of cytochrome P450 3A4 and reductase domain of Bacillus
      megaterium BM3 (BMR). Here we report the direct electrochemistry of 3A4-BMR
      chimeras immobilised on glassy carbon electrodes and we investigated the effect
      of inter-domain loop length and immobilising environment flexibility on both
      redox properties and electrocatalysis. We observe that redox potential can be
      modulated by the linker length and the immobilising layer flexibility. In
      addition, enzyme inter-domain dynamics and environment flexibility also modulate
      3A4-BMR turnover efficiency on electrode system. Vmax values are increased up to
      about 100% in the presence of testosterone and up to about 50% in presence of
      tamoxifen by decreasing immobilising film rigidity. The effect on 3A4-BMR Vmax
      values is dependent on inter-domain loop length with 3A4-5GLY-BMR chimera being
      the more affected. The underlying reason for these observations is the potential
      motion of the FMN domain that is the key to shuttle electrons from FAD to haem.

PMID- 30098473
TI  - The prospective relationship between postpartum PTSD and child sleep: A 2-year
      follow-up study.
AB  - BACKGROUND: The main aim of this study was to examine the prospective impact of
      maternal postpartum PTSD on several standardized child sleep variables two years
      postpartum in a large, population-based cohort of mothers. Moreover, we
      investigated the influence of numerous potential confounding maternal and child
      factors. Finally, we tested potential reverse temporal associations between child
      sleep eight weeks postpartum and maternal PTSD symptoms two years postpartum.
      METHODS: This study is part of the population-based Akershus Birth Cohort, a
      prospective cohort study at Akershus University Hospital, Norway. Data from the
      hospital's birth record, from questionnaires at 17 weeks gestation, eight weeks
      and two years postpartum were used. At two years postpartum, 39% of the original
      participants could be retained, resulting in a study population of n = 1480. All
      child sleep variables significantly correlated with postpartum PTSD symptoms were
      entered into multiple linear regression analyses, adjusting for confounding
      factors. RESULTS: Postpartum PTSD symptoms were related to all child sleep
      variables, except daytime sleep duration. When all significant confounding
      factors were included into multivariate regression analyses, postpartum PTSD
      symptoms remained a significant predictor for number and duration of night
      wakings (beta = 0.10 and beta = 0.08, respectively), duration of settling time
      (beta = 0.10), and maternal rating of their child's sleep problems (beta = 0.12,
      all p<.01. Child sleep at eight weeks postpartum was not significantly related to
      maternal sleep two years postpartum when controlling for postpartum PTSD at eight
      weeks. LIMITATIONS: Child outcomes were based on maternal reporting and might be
      influenced by maternal mental health. CONCLUSIONS: Our results showed for the
      first time that maternal postpartum PTSD symptoms were prospectively associated
      with less favorable child sleep, thus increasing the risk of developmental or
      behavioral problems through an indirect, but treatable pathway. Early detection
      and treatment of maternal postpartum PTSD may prevent or improve sleep problems
      and long-term child development.

PMID- 30098475
TI  - NT-proBNP and CA 125 levels are associated with increased pro-inflammatory
      cytokines in coronary sinus serum of patients with chronic heart failure.
AB  - PURPOSE: Heart failure (HF) is considered to be a complex syndrome associated
      with neurohormonal and cytokine activation, that contribute to its progression.
      There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor
      marker widely used for ovarian cancer therapy monitoring, was significantly
      elevated in HF patients. We hypothesized that inflammatory stimuli may be
      responsible for amino-terminal fragment of the prohormone B-type natriuretic
      peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF). We
      aimed to measure the levels of NT-proBNP, CA 125, pro-anti-inflammatory cytokines
      (IL-6, IL-1beta, IL-8, TNF-alpha and IL-4), from peripheral venous (PV) and
      coronary sinus (CS) blood samples, in patients with CHF and to assess their
      correlation with echocardiographic indices. METHODS: We enrolled 32 subjects
      (20M/12F) with CHF (III-IV NYHA functional class) who were to undergo cardiac
      resynchronization therapy (CRT) device implantation and 30 healthy controls
      (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT
      for each CHF patient. Serum levels of biomarkers were measured by ELISA. Cardiac
      function was assessed echocardiographically. RESULTS: All investigated biomarkers
      were significantly higher in CHF patients than in non-CHF controls (P < 0.001).
      There were positive correlations between biomarkers concentrations in PV and CS
      (r between 0.54 and 0.98, all P < 0.003). NT-proBNP, IL-6 and IL-1beta levels
      were 17%, 86% and 36% higher in CS than in PV, these increases being very well
      correlated each other, while CA 125 levels were 86% higher in PV than in CS.
      Moreover, CS NT-proBNP, CS IL-6 and CS IL-1beta serum concentrations were
      inversely related to the echocardiographically determined left ventricular
      ejection fraction (LVEF) (r = -0.61, P < 0.001; r = -0.71, P < 0.001 and r = 
      0.48, P = 0.005, respectively). A positive relationship was found between CA 125
      and IL-1beta (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL-6 (r =
      0.43, P = 0.015), TNF-alpha (r = 0.46, P = 0.008) in PV serum. CA 125
      concentrations were closely related to NT-proBNP both in CS (r = 0.46, P = 0.008)
      and PV (r = 0.52, P = 0.002). CONCLUSIONS: CS sampling of NT-proBNP, CA 125 and
      pro-anti-inflammatory cytokines provides an additional insight into the possible
      mechanisms by which these biomarkers lead to left ventricular remodeling. Our
      results clearly suggest that serum NT-proBNP and CA 125 levels not only in PV,
      but also in CS of patients with CHF, may be dependent on inflammation as a
      consequence of cytokine network activation.

PMID- 30098474
TI  - A Plasma Long Noncoding RNA Signature for Early Detection of Lung Cancer.
AB  - The early detection of lung cancer is a major clinical challenge. Long noncoding
      RNAs (lncRNAs) have important functions in tumorigenesis. Plasma lncRNAs directly
      released from primary tumors or the circulating cancer cells might provide cell
      free cancer biomarkers. The objective of this study was to investigate whether
      the lncRNAs could be used as plasma biomarkers for early-stage lung cancer. By
      using droplet digital polymerase chain reaction, we determined the diagnostic
      performance of 26 lung cancer-associated lncRNAs in plasma of a development
      cohort of 63 lung cancer patients and 33 cancer-free individuals, and a
      validation cohort of 39 lung cancer patients and 28 controls. In the development
      cohort, 7 of the 26 lncRNAs were reliably measured in plasma. Two (SNHG1 and
      RMRP) displayed a considerably high plasma level in lung cancer patients vs.
      cancer-free controls (all P < .001). Combined use of the plasma lncRNAs as a
      biomarker signature produced 84.13% sensitivity and 87.88% specificity for
      diagnosis of lung cancer, independent of stage and histological type of lung
      tumor, and patients' age and sex (all P > .05). The diagnostic value of the
      plasma lncRNA signature for lung cancer early detection was confirmed in the
      validation cohort. The plasma lncRNA signature may provide a potential blood
      based assay for diagnosing lung cancer at the early stage. Nevertheless, a
      prospective study is warranted to validate its clinical value.

PMID- 30098477
TI  - The brain metabolic signature of visual hallucinations in dementia with Lewy
      bodies.
AB  - Visual hallucinations (VH) are a core clinical feature of dementia with Lewy
      bodies (DLB), but their specific neural substrate remains elusive. We used 18F
      FDG-PET to study the neural dysfunctional signature of VH in a group of 38 DLB
      patients (mean age+/-SD 72.9 +/- 7.5) with available anamnestic records,
      cognitive and neurological examination and NeuroPsychiatric Inventory assessing
      VH. We tested the voxel-wise correlation between 18F-FDG-PET hypometabolism and
      VH NPI scores at the whole-group level, then adopting inter-regional correlation
      analysis to explore the resting-state networks (RSNs) metabolic connectivity in
      DLB patients with and without visual hallucinations, as compared to N = 38 age
      matched healthy controls (HCs) (mean age+/-SD 71.5 +/- 6.9). At the whole-group
      level, we found a negative correlation between VH NPI scores and 18F-FDG-PET
      hypometabolism in the right occipito-temporal cortex (p < .001 uncorrected, p <
      .05 Family-Wise Error cluster-corrected). Then, splitting the group according to
      VH presence, we found that DLB non-hallucinators presented a pattern of
      connectivity seeding from this occipito-temporal cluster and extending to the
      ventral visual stream. At difference, the DLB hallucinators showed a metabolic
      connectivity pattern limited to the occipital-dorsal parietal regions. As for
      RSNs, both the DLB subgroups showed a markedly reduced extent of attention and
      visual networks compared to HCs, with a variable alteration in the topography.
      DLB-VH patients showed a more pronounced shrinkage of the primary visual network,
      which was disconnected from the higher visual hubs, at difference with both HC
      and DLB non-hallucinators. These findings suggest that an altered brain metabolic
      connectivity within and beyond visual systems may promote VH in DLB. These
      results support the most recent neurocognitive models interpreting VH as the
      result of an inefficient recruitment of the ventral visual stream and of a large
      scale multi-network derangement.

PMID- 30098476
TI  - Adipokine interactions promote the pathogenesis of systemic lupus erythematosus.
AB  - BACKGROUND: Adipokines are chemical mediators released from adipose tissue
      involved in regulation of appetite, insulin sensitivity, immune system and
      inflammatory responses. Adipokines contributes to low grade inflammatory response
      in autoimmune disease like Systemic Lupus Erythematosus (SLE) but the
      pathophysiology is yet not clear. The aim of this study is to understand role of
      adipokine interactions in SLE disease pathogenesis. METHODS: Sixty newly
      diagnosed treatment naive SLE patients fulfilling the ACR criteria and forty age
      sex matched healthy subjects were enrolled in thiscase-control study. Disease
      activity in SLE patients was evaluated using SELENA-SLEDAI. Array of adipokines,
      C1q circulating immune complexes (C1q-CIC), anti-C1q, anti-ribososmal P0 (anti
      RibP0) and anti-mitochondrial antibodies (AMA) levels were detected by ELISA.
      Antinuclear antibodies (ANA) and anti-dsDNA autoantibodieswere detected by
      Indirect Immunofluorescence (IIF), while antigen specificities were detected by
      Immunoassay blot. Serum levels of C3 and C4 complement factors were assessed by
      nephlometer. RESULTS: Statistically significant elevation in progranulin, adipsin
      and resistin levels was seen among SLE patients when compared to healthy controls
      (p < 0.0001). Leptin and omentin levels were significantly reduced in SLE
      patients (p < 0.0001). There was no statistically significant difference in serum
      adiponectin, chemerin and visfatin levels when these two groups were compared (p
      > 0.05). Adiponectin, adipsin and resistin levels were elevated in SLE patients
      with renal manifestations (p < 0.05). Reduced leptin levels were significantly
      associated with presence of renal manifestations (p < 0.05). Adiponectin levels
      positively correlated with disease activity (r = 0.294, p = 0.027) whereas
      negatively correlated with C3 levels (r = -0.439, p = 0.0007). A positive
      correlation was observed between hypocomplementemia and leptin levels (p < 0.05).
      Leptin levels were negatively correlated with disease activity, anti-dsDNA, C1q
      CIC and anti-C1q levels (p < 0.05). A significant positive correlation was
      observed between progranulin levels and anti-ribosomal P0 antibodies (r = 0.499,
      p < 0.0001). CONCLUSION: Adipokines levels and associated clinical manifestations
      suggest involvement of adipokines in disease pathogenesis of SLE. SLE disease
      activity and complement components may suggest regulatory effect of adipokines
      (adiponectin and leptin) on disease pathogenesis. Further studies on adipokines
      in SLE patients with renal manifestations may propose them as prognostic markers
      in renal damage. TRIAL REGISTRATION: NA.

PMID- 30098478
TI  - Meticulous optimization of cardiomyocyte yields in a 3-stage continuous
      integrated agitation bioprocess.
AB  - Human pluripotent stem cells (hPSCs) can be a renewable source for generating
      cardiomyocyte (CM) for treating myocardial infraction. In our previous
      publication, we described an integrated microcarrier-based wave reactor process
      for the expansion and differentiation of hPSCs to CMs on a rocker based platform.
      However, this platform is limited in terms of linear scalability and CMs purity.
      The present study describes ways to overcome these limitations by the use of a
      stirred scalable platform and incorporation of an additional lactate based
      purification step which increases CM purity. Efficient CM differentiation in
      stirred spinners was achieved by (1) Addition of ascorbic acid (AS) during the
      differentiation phase which resulted in an increase of 38.42% in CM yield (0.84
      +/- 0.03 * 106vs 1.17 +/- 0.07 * 106 CM/mL for cultures without AS and with AS
      respectively) and (2) Change of agitation regime to a shorter static intervals
      one (from 66 min off/6 min on (66/6) to 8 min off/1 min on (8/1)) during the
      first 3 days of differentiation which resulted in 22% increase in CM yield (1.50
      +/- 0.10 * 106vs 1.23 +/- 0.07 * 106 CM/mL). The combination of AS addition and
      change in agitation regime resulted in a production yield of 1.50 +/- 0.10 * 106
      CM/mL which is comparable to that achieved in the rocker platform as described
      before (1.61 +/- 0.36 * 106 CM/mL). Increase in CM purity was achieved by
      changing of culture medium to RPMI1640 (without glucose) + 5 mM lactate +0.6 mM
      AS at day 10 of differentiation which resulted in 44.5% increase in CM purity at
      day 15. The increase in purity of CMs was due to the death of the non-CM cells
      (~76% of cell death). It is important to note that in the absence of glucose,
      lactate was consumed at a rate of 0.01 mmol/106 cells/h. Addition of glucose,
      even in small amounts, during the purification step prevents the process of CM
      purification, due to the growth of the non-CM cell population. In summary, hPSC
      (hESC-HES3 and hiPSC-IMR90) can be efficiently differentiated to CMs in a
      scalable spinner process which integrates 7 days of expansion (3.01 +/- 0.51 *
      106 to 3.50 +/- 0.65 * 106 cells/mL) followed by 10 days of WNT modulated CM
      differentiation and 5 days of lactate based purification. CM yield of 1.38 +/-
      0.22 * 106 to 1.29 +/- 0.42 * 106 CM/mL with 72.5 +/- 8.35% to 83.12 +/- 8.73%
      cardiac troponin-T positive cells were obtained from these cultures.

PMID- 30098479
TI  - Obsessive-compulsive tendencies are related to seeking proxies for internal
      states in everyday life.
AB  - BACKGROUND AND OBJECTIVES: In recent years we have proposed and investigated the
      Seeking Proxies for Internal States (SPIS) model of obsessive-compulsive disorder
      (OCD), which postulates that deficient access to internal states is a key feature
      of the disorder. According to this model, rules and rituals that often
      characterize people with OCD can be understood as proxies for deficiently
      accessible internal states. Here we compliment this earlier experimental work by
      examining whether reliance on proxies for internal states in everyday life is
      associated with OCD. METHODS: We developed an inventory for assessing reliance on
      proxies in everyday life and examined its relationship with obsessive-compulsive
      tendencies in two internet panel studies. The internal states included hunger,
      enjoyment, interpersonal liking, preferences, a sense of understanding, and
      intuitions about correct solutions to problems. The proxies included one's own
      behavior, the opinion of others, and objective indices such as grades and elapsed
      time since eating. RESULTS: In both studies, participants with obsessive
      compulsive tendencies reported relying more on external, discernible proxies for
      a variety of internal states. These results remained significant after
      controlling for concurrent anxiety and depression. LIMITATIONS: Our inventory is
      by necessity limited in its sampling of internal states and proxies and further
      correlational and experimental studies will be needed to examine additional areas
      of application, such as decision making and interpersonal liking. CONCLUSIONS:
      These results are consistent with and expand the Seeking Proxies for Internal
      States (SPIS) model and may have implications for understanding and treating
      individual with OCD.

PMID- 30098480
TI  - White light color tuning ability of hybrid Dibenzoylmethane/YAG:Ce nanophosphor.
AB  - In this study, we have considered the synthesis of a novel hybrid material
      consisting of cerium-doped yttrium aluminium garnet (YAG:Ce) nanophosphor surface
      decorated by UV/blue sensitizing Dibenzoylmethane (DBM) organic molecule. A
      comparative evaluation of synthesized hybrid material YAG:Ce/DBM nanophosphor and
      YAG:Ce nanophosphors was made using a combination of different analytical
      techniques like X-ray diffraction, Scanning electron microscopy, UV-Visible
      Infrared absorption, Photoluminescence techniques etc. Due to the presence of
      organic ligand, the hybrid nanophosphor has extended excitation. We have
      monitored the emission spectra at excitation with 355 nm, 375 nm, 405 nm, and 465
      nm. The synthesized luminescent hybrid material was characterized by various
      spectroscopic techniques and its photophysical properties were thoroughly
      investigated. The color perception of hybrid YAG:Ce/DBM nanophosphor is
      significantly modified due to the mixing of blue color in the green-yellow
      emission of YAG:Ce nanophosphor at different excitations which yield CIE
      coordinates (0.37, 0.59).

PMID- 30098483
TI  - Geographic conditioning in dietary, social, and health patterns in elderly
      population with disabilities.
AB  - OBJECTIVE: The aim of this study was to identify the most relevant variables
      defining the dietary, social, and health patterns of elderly populations with
      disabilities, considering their geographic profile. METHODS: A cross-sectional
      study was carried out in a sample of 354 disabled, free-living elderly adults
      from three different geographic profiles (metropolitan, rural, and mixed
      profile). The dietary data were obtained through a validated food habit
      questionnaire. The data regarding health status, cohabitation unit, and social
      benefits were obtained through the public social services. A standardized
      principal component analysis was used to select the most relevant variables, by
      considering their contributions to each principal component and their relation
      with the geographic factor. RESULTS: From 131 variables, we highlighted 27
      (57.37% of variability explained). The variables with more contribution are, in
      order, the calorie intake (especially from lipids), absence of home assistance,
      and the difference between intake and recommended calories. The procedure was
      validated by assessing the prediction using a multinomial logistic regression
      model (88.2% and 66.7% of success rate regarding the metropolitan and rural
      profiles, respectively). There is a differentiated behavior based on the
      geographic origin of individuals, specifically regarding caloric intake, number
      of diseases, and the requirement for home assistance. CONCLUSIONS: Older adults
      living in a metropolitan are tend to have a greater number of diseases as well as
      a lower caloric intake. The increased rural caloric consumption comes from
      lipids. Better health status in rural areas is associated with a lower need for
      home assistance.

PMID- 30098481
TI  - Synthesis of a 3'-C-ethynyl-beta-d-ribofuranose purine nucleoside library:
      Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides.
AB  - A focused nucleoside library was constructed around a 3'-C-ethynyl-d-ribofuranose
      sugar scaffold, which was coupled to variously modified purine nucleobases. The
      resulting nucleosides were probed for their ability to inhibit tumor cell
      proliferation, as well as for their activity against a panel of relevant human
      viruses. While C6-aryl substituted purine nucleosides were found to be weakly
      active, several C7-substituted 7-deazapurine nucleosides elicited potent
      antiproliferative activity. Their activity spectrum was evaluated in the NCI-60
      tumor cell line panel indicating activity against several solid tumor derived
      cell lines. Analog 32, equipped with a 7-deaza 7-chloro-6-amino-purin-9-yl base
      was evaluated in a metastatic breast tumor (MDA-MB-231-LM2) xenograft model. It
      inhibited both tumor growth and reduced the formation of lung metastases as
      revealed by BLI analysis. The dideazanucleoside analog 66 showed interesting
      activity against hCMV. These results highlight the potential advantages of
      recombining known sugar and nucleobase motifs as a library design strategy to
      discover novel antiviral or antitumor agents.

PMID- 30098482
TI  - Pyrazinyl ureas revisited: 1-(3-(Benzyloxy)pyrazin-2-yl)-3-(3,4
      dichlorophenyl)urea, a new blocker of Abeta-induced mPTP opening for Alzheimer's
      disease.
AB  - Herein, we report synthesis and evaluation of new twenty-eight pyrazinyl ureas
      against beta amyloid (Abeta)-induced opening of mitochondrial permeability
      transition pore (mPTP) using JC-1 assay which measures the change of
      mitochondrial membrane potential (DeltaPsim). The neuroprotective effect of
      seventeen compounds against Abeta-induced mPTP opening was superior to that of
      the standard Cyclosporin A (CsA). Among them, 1-(3-(benzyloxy)pyrazin-2-yl)-3
      (3,4-dichlorophenyl)urea (5) effectively maintained mitochondrial function and
      cell viabilities on ATP assay and MTT assay. Also, hERG channel assay presented
      safe cardiotoxicity profile for compound 5. In addition, using CDocker algorithm,
      a molecular docking model presented a plausible explanation for the elicited
      differences in efficiencies of the synthesized compounds to reduce the green to
      red fluorescence as indication of mPTP closure. Hence, this report presents
      compound 5 as the most promising pyrazinyl urea-based mPTP blocker up to date.

PMID- 30098484
TI  - Systematic reviews of economic burden and health-related quality of life in
      patients with acute myeloid leukemia.
AB  - BACKGROUND: Acute myeloid leukemia (AML) is a rare hematologic malignancy largely
      affecting older adults. Comorbidities may compromise fitness and eligibility for
      high-intensity chemotherapy (HIC). This study presents the results of two
      systematic reviews (SRs) assessing (1) the impact of AML and current treatments
      on health-related quality of life (HRQoL), and (2) the economic burden and cost
      drivers of AML in patients who are ineligible for HIC. METHODS: Electronic
      searches (MEDLINE, EMBASE, EconLit, Cochrane library) were supplemented with
      manual searching of conference, utility, and HTA databases. All studies reporting
      HRQoL or economic data for patients with AML who were ineligible for HIC were
      included. RESULTS: The HRQoL SR included ten studies. Patients with AML have
      lower baseline HRQoL than other cancer patients or the general population, and
      those receiving lower intensity treatment have lower HRQoL than those eligible
      for HIC. Low baseline HRQoL predicts poor outcomes, and treatment had variable
      effects on HRQoL. The economic burden SR included nine studies. Medical costs
      varied widely, reflecting the heterogeneity of AML. Hospitalization is a key cost
      driver in AML treatment but was largely not considered in cost studies. Medical
      resource utilization comprised drug acquisition, drug administration, disease
      monitoring tests, transfusions, adverse event management, supportive
      care/monitoring costs and terminal care. CONCLUSION: As new drugs emerge that
      extend survival, assessment of HRQoL will be important to evaluate the quality of
      that survival. Cost data, driven by transfusions and hospitalization, will be
      important to evaluate the economic value of new treatments.

PMID- 30098485
TI  - Clinical benefit of controversial first line systemic therapies for advanced
      stage ovarian cancer - ESMO-MCBS scores.
AB  - BACKGROUND: The magnitude of clinical benefit scale (MCBS) was introduced by the
      European Society of Medical Oncology (ESMO) to quantify the clinical benefit of
      therapeutic regimens and to prioritise therapies. It distinguishes curative from
      palliative treatments and ranks their benefit based on overall survival (OS),
      progression free survival (PFS), quality of life (QoL) and toxicity. Objective of
      this study on the first line treatment of ovarian cancer was to evaluate the
      evidence for the current standard of care using the ESMO-MCBSv1.1 with an
      emphasis on controversial therapeutic options: intraperitoneal chemotherapy, dose
      dense paclitaxel and bevacizumab. METHODS: Phase III trials, published since
      1992, investigating first line systemic treatment of Federation Internationale de
      Gynecologie et d'Obstetrique (FIGO) stage IIB-IV epithelial ovarian cancer were
      included. Since most studies included patients with FIGO stage IV disease or
      incomplete debulking, all treatments were judged to be palliative. Treatments
      were graded 5 to 1 on the ESMO-MCBSv1.1, where grades 5 and 4 represent a high
      level of clinical benefit. RESULTS: 55 studies met the inclusion criteria. ESMO
      MCBS scores were calculated for eleven studies that showed a statistically
      significant benefit of the experimental treatment. Intraperitoneal (ip) cisplatin
      scored a 4 and 3, but two other studies were negative and therefore not scored on
      the ESMO-MCBS. Dose-dense paclitaxel showed substantial clinical benefit in one
      study (score 4), but three studies were negative. Addition of bevacizumab also
      scored a 4 in one study subgroup including high-risk patients but a 2 in another
      trial with a larger study population. CONCLUSION: Based on ESMO-MCBS scores, dose
      dense paclitaxel and intraperitoneal chemotherapy cannot be recommended as
      standard treatment. Bevacizumab should be considered only in the high-risk
      population. The ESMO-MCBSv1.1. helps to summarise reported studies on
      controversial treatment regimens, and identifies their weaknesses.

PMID- 30098486
TI  - Emotional and cognitive correlates of hating among adolescents: An exploratory
      study.
AB  - INTRODUCTION: The phenomenon of hate is becoming common among adolescents, but is
      little investigated by literature. Typically the haters leave their insults on
      the victim's social pages to denigrate another person, famous or not. In the
      literature, to date, there are no scientific studies that have explored
      psychological variables linked to these behaviors. The aim of this study was to
      evaluate the psychological correlates of pathological worry and cognitive
      distortions (CD) related to hating behaviors. METHODS: Participants (202 female
      and 200 male, mean age 14.9) of this study completed the Hating Adolescents Test
      (HAT), the Penn State Worry Questionnaire (PSWQ), and the How I Think
      Questionnaire (HITQ). RESULTS: Preliminary results show significant gender
      differences in the variables of the study: on hating and CD "minimizing," males
      reported higher scores than females, and females scored higher than males on
      pathological worry. The mediation model suggests that the CD "assuming the worst"
      is a mediator in the relationships between pathological worry and hating
      behaviors. CONCLUSIONS: The study suggests how the tendency towards pathological
      worry influences hatred among adolescents, but a relevant component is
      represented by the tendency to distort information and to consider ambiguous
      situations as hostile. The implications of these findings for future theoretical
      and empirical research in this field are discussed.

PMID- 30098487
TI  - Adolescent sleep insufficiency one year after high school.
AB  - INTRODUCTION: Sleep difficulties affect approximately 45% of adolescents and are
      associated with health consequences such as depression and obesity. Sleep
      duration immediately following high school is not well understood, especially for
      those not pursuing post-secondary education. We examined adolescent sleep
      insufficiency and its association with school and work status. METHODS: Data were
      collected in 2012 and 2013 as part of the NEXT Generation Health Study (NEXT), a
      nationally representative, longitudinal study of U.S. adolescents. Self-reported
      sleep was compared with guidelines for healthy sleep. RESULTS: On weekdays, 31%
      reported less than 7 h of sleep; which reduced to 6% on weekends. Average weekday
      sleep was 7.4 h and weekend sleep was 9.2 h. Few results emerged from interaction
      analyses comparing different work and school statuses. CONCLUSIONS: This study
      captures sleep habits of adolescents one year after high school regardless of
      school and/or working status. Implications and future directions are discussed.

PMID- 30098488
TI  - Steady-state evoked potentials distinguish brain mechanisms of self-paced versus
      synchronization finger tapping.
AB  - Sensorimotor synchronization (SMS) requires aligning motor actions to external
      events and represents a core part of both musical and dance performances. In the
      current study, to isolate the brain mechanisms involved in synchronizing finger
      tapping with a musical beat, we compared SMS to pure self-paced finger tapping
      and listen-only conditions at different tempi. We analyzed EEG data using
      frequency domain steady-state evoked potentials (SSEPs) to identify sustained
      electrophysiological brain activity during repetitive tasks. Behavioral results
      revealed different timing modes between SMS and self-paced finger tapping,
      associated with distinct scalp topographies, thus suggesting different underlying
      brain sources. After subtraction of the listen-only brain activity, SMS was
      compared to self-paced finger tapping. Resulting source estimations showed
      stronger activation of the left inferior frontal gyrus during SMS, and stronger
      activation of the bilateral inferior parietal lobule during self-paced finger
      tapping. These results point to the left inferior frontal gyrus as a pivot for
      perception-action coupling. We discuss our findings in the context of the ongoing
      debate about SSEPs interpretation given the variety of brain events contributing
      to SSEPs and similar EEG frequency responses.

PMID- 30098489
TI  - Evaluation of free thyroxine determination based on one-step fluorometric
      immunoassay technique and the suboptimal concordance with two-step immunoassay.
AB  - Free thyroxine (FT4) quantification is continuing to be a concern. The purpose of
      the following study was to evaluate the analytical performance of Tosoh AIA900
      based on a one-step technique and its comparison to Access 2 (two-step technique)
      over different clinical contexts (euthyroid, thyroid disorders, uncontrolled
      diabetes, renal failure and pregnancy). The protocol established by the French
      society of Clinical Biology was used to evaluate: imprecision, limit of
      detection, trueness, linearity, interferences and method comparisons. Within-run
      variation of 3.1%, 5.7% and 4.4% were found for the low, medium and high
      controls, respectively. Between-run was 5.8% for low control, 5.7% for medium
      control and 7.1% for high control. Common interferences did not affect one-step
      immunoassay FT4 results. The linearity was checked up to 86 pmol/L. The limit of
      detection was 5.5 pmol/L. The concordance correlation coefficient (CCC) showed a
      low agreement (0.6) between both methods. Bland-Altman plot revealed that AIA 900
      one-step immunoassay technique provides a significant higher values ((+2.8 +/-
      2.7 pmol/L;p < 0.0001). The Passing-Bablok regression demonstrated both
      proportional and systematic differences in comparison to Access 2. The lowest
      association was noted in subjects with impaired renal function (CCC = 0.27). At
      the time of the study, the results of on-step immunoassay are not directly
      comparable with Access 2.

PMID- 30098490
TI  - Impact of electrode micro- and nano-scale topography on the formation and
      performance of microbial electrodes.
AB  - From a fundamental standpoint, microbial electrochemistry is unravelling a
      thrilling link between life and materials. Technically, it may be the source of a
      large number of new processes such as microbial fuel cells for powering remote
      sensors, autonomous sensors, microbial electrolysers and equipment for effluent
      treatment. Microbial electron transfers are also involved in many natural
      processes such as biocorrosion. In these contexts, a huge number of studies have
      dealt with the impact of electrode materials, coatings and surface
      functionalizations but very few have focused on the effect of the surface
      topography, although it has often been pointed out as a key parameter impacting
      the performance of electroactive biofilms. The first part of the review gives an
      overview of the influence of electrode topography on abiotic electrochemical
      reactions. The second part recalls some basics of the effect of surface
      topography on bacterial adhesion and biofilm formation, in a broad domain
      reaching beyond the context of electroactivity. On these well-established bases,
      the effect of surface topography is reviewed and analysed in the field of
      electroactive biofilms. General trends are extracted and fundamental questions
      are pointed out, which should be addressed to boost future research endeavours.
      The objective is to provide basic guidelines useful to the widest possible range
      of research communities so that they can exploit surface topography as a powerful
      lever to improve, or to mitigate in the case of biocorrosion for instance, the
      performance of electrode/biofilm interfaces.

PMID- 30098491
TI  - Automated determination of cardiac rest period on whole-heart coronary magnetic
      resonance angiography by extracting high-speed motion of coronary arteries.
AB  - PURPOSE: The aim of the present study was to develop an automated system for
      determining the cardiac rest period during whole-heart coronary magnetic
      resonance angiography (CMRA) examination. MATERIALS AND METHODS: Ten healthy male
      volunteers (25-51 years old, 50-77 beats/min heart rate) were enrolled in this
      prospective study. A motion area map was generated from a cine image set by
      extracting high-speed component of cardiac motion, and it was used to specify the
      rest period in the proposed CMRA. In conventional CMRA, the rest period was
      determined based on the visual inspection of cine images. Agreement of the start
      time, end time, and trigger time between the two methods was assessed by the
      Bland-Altman plot analysis. Two observers visually evaluated the quality of the
      curved planar reformation (CPR) image of the coronary arteries. RESULTS: The
      proposed method significantly prolonged the start time (mean systematic
      difference 37.7 ms, P < 0.05) compared with the conventional method. Good
      agreement was observed for the end time (mean systematic difference 8.9 ms) and
      trigger time (mean systematic difference -28.8 ms) between the two methods. A
      significantly higher image quality (P < 0.05) was provided for the left
      circumflex artery in the proposed CMRA (mean grading score 3.88) than in
      conventional CMRA (mean grading score 3.68). CONCLUSION: Our system enabled
      detection of the rest period automatically without operator intervention and
      demonstrated somewhat higher image quality compared with conventional CMRA. Its
      use may be useful to improve the imaging workflow for CMRA in clinical practice.

PMID- 30098492
TI  - High Body Mass Index is associated with an expansion of endometrial T Regulatory
      cell and macrophage populations.
AB  - Obesity is associated with implantation failure, miscarriage, low-grade
      inflammation and a reduction in peripheral immune-suppressive T regulatory (Treg)
      cells. Therefore, we postulated that this reduction may also extend to the
      endometrium and cause embryonic loss. In a cohort of 40 infertile women, without
      implantation failure or recurrent miscarriage, we examined the density of Treg
      cells, macrophages and natural killer (NK) cells in mid-luteal endometrial
      biopsies. Significant positive correlations were observed between BMI and
      endometrial Treg cells and macrophages, but no relationship with NK cells. We
      postulate that this change may be a positive adaption to minimise adiposity
      related inflammation.

PMID- 30098493
TI  - Methane emission during on-site pre-storage of animal manure prior to anaerobic
      digestion at biogas plant: Effect of storage temperature and addition of food
      waste.
AB  - This study investigated the temperature dependency of CH4 emission from pre
      storage of animal manure prior to anaerobic digestion at 15, 20, 25 and 30 
      degrees C using lab-scale anaerobic digesters. The manure was added and removed
      daily to simulate the pre-storage process at biogas plants. CH4 emission
      accounted for 1-46% of total CH4 potential from pig manure (PM) and 1-2% of that
      from cattle manure (CM) at the investigated temperatures, with significant
      increases above 25  degrees C. Addition of food waste (FW) reduced the CH4
      emission when storage temperature was 20  degrees C or lower for PM and 25 
      degrees C or lower for CM due to volatile fatty acid accumulation and lower pH
      (<5.5) but emissions increased with higher storage temperatures.

PMID- 30098494
TI  - Can electrochemistry enhance the removal of organic pollutants by
      phytoremediation?
AB  - An electrokinetic-assisted phytoremediation test using maize (Zea mays L.) was
      conducted in order to assess the role of the electric field on the enhancement of
      plant uptake and degradation of the moderate polar pesticide atrazine in spiked
      soils. Twelve different treatments, including two different initial atrazine soil
      doses (5 and 10 mg kg-1) and two different values of the electric field applied
      (2 and 4 V cm-1), together with the corresponding control treatments without
      plants and/or without electric current, were tested. The application of an
      electric field during a period of 4 h a day and with periodical polarity
      inversion (each 2 h) did not caused significant changes in soil pH; moreover,
      maize plants increased the buffering capacity of the soil. The application of an
      electric field of 2 V cm-1 led to a slight decrease on maize biomass while the
      accumulation of atrazine and its main metabolites in plant tissues was
      significantly enhanced. On the overall, the yield of atrazine removal by
      electrokinetic-assisted phytoremediation with maize was increased up to 36.5%
      with respect to the phytoremediation process without electricity. On our
      knowledge, this work is the first one specifically focused on the removal of
      organic pollutants from soils by using the combination of phytoremediation and
      electrokinetic remediation.

PMID- 30098495
TI  - Green roof and photovoltaic panel integration: Effects on plant and arthropod
      diversity and electricity production.
AB  - The combination of green roofs with photovoltaic (PV) panels has been proposed to
      provide synergistic benefits as the panel is cooled by the presence of the
      vegetation, and thus produces more electricity, while the solar panel enhances
      growing conditions for vegetation, and increases abiotic heterogeneity, resulting
      in higher plant diversity. We tested these hypotheses in a non-irrigated green
      roof in a Mediterranean climate with replicated plots including green roofs only,
      green roofs with a PV panel, and a conventional roof surface with a PV panel. We
      found that presence of a panel resulted in higher heterogeneity in substrate
      moisture, but there was no effect on plant diversity. Plant species showed
      enhanced growth in plots with PV, including greater growth of Sedum sediforme and
      longer flowering time of annual species. On the other hand, arthropod diversity
      was lower during part of the year, and abundance of some arthropod taxa was lower
      in green roof plots with PV. The presence of the green roof also did not improve
      electricity production by the panels. We conclude that in a Mediterranean
      climate, it would be appropriate to examine the use of irrigation in green roofs
      with PV panels, including effects on the plant community and on electricity
      production.

PMID- 30098496
TI  - Hydrological responses to land degradation in the Northwest Benin Owena River
      Basin, Nigeria.
AB  - Adequate insights into how land degradation alters the hydrology of river basins
      will help forecast the hydrological impacts of land cover change dynamics,
      thereby providing unique information required for sustainable river basin
      management. This study attempts to utilize a multi-dimensional methodology
      involving the application of the physically based Soil and Water Assessment Tool
      (SWAT) hydrological model and Partial Least Square regression (PLSR) statistical
      model to evaluate the response of the hydrological components within the
      Northwest Benin Owena River Basin (NWBORB) in Nigeria to land degradation. Using
      the historic land cover maps of 1986, 2002, and 2015, covering the basin, the
      SWAT model was employed to simulate the hydrological components for each historic
      year. The PLSR model was utilized to establish a response relationship between
      land cover changes and hydrological component modification within the basin.
      Results showed that between 1986 and 2015, 18.56% of the forest was lost, with a
      major portion (16.19%) gained by plantation. Consequently, annual water yield and
      surface runoff increased by 18.28% and 17.26% respectively, while annual base
      flow and actual evapotranspiration decreased by 22.58% and 21.72% respectively.
      The reduction in forest is strongly correlated with an increase in plantation (
      0.833), surface runoff component (-0.723) and water yield (-0.532). Also,
      expansion of plantation land is strongly correlated with surface runoff
      components (0.877) and negatively correlated with base flow component (-0.573).
      Variable Importance of the Projections (VIP) from the PLSR model showed forest
      (VIP = 1.23), Plantation land (VIP = 1.02) as the most important land cover
      variables altering the basins' local hydrology. The study clearly shows that
      forest preservation plays an important role in the regulation of water resources
      within a river basin. This methodology can be replicated for poorly gauged river
      basins provided the land cover maps and stream discharge data are available.

PMID- 30098497
TI  - Octreotide attenuates hepatic fibrosis and hepatic stellate cells proliferation
      and activation by inhibiting Wnt/beta-catenin signaling pathway, c-Myc and cyclin
      D1.
AB  - Fibrosis is the common results from an excessive wound-healing response to
      chronic liver injury. Otreotide (OCT), an analogue of somatostatin, was reported
      to have an anti-hepatic fibrosis effect. However, its anti-fibrosis mechanisms
      have not been well characterized to date. The present study aimed to investigate
      the protective effects of OCT on carbon tetrachloride (CCl4)-induced rat liver
      fibrosis and activation and proliferation of transforming growth factor-beta1
      (TGF-beta1)-treated hepatic stellate cells (HSCs) and explore its anti
      hepatofibrotic mechanisms. Our results indicated that treatment with OCT markedly
      down-regulated the protein and mRNA expression of liver fibrosis markers
      including alpha-smooth muscle actin (alpha-SMA) and collagen I in CCl4-induced
      rat model of liver fibrosis, accompanied by decreasing aspartate transaminase
      (AST), alanine transaminase (ALT), total bilirubin (TBIL) activities and
      increasing the serum level of albumin (ALB). In addition, in vitro results
      revealed that OCT inhibited the activation and proliferation of TGF-beta1-treated
      LX-2 cells in a concentration-dependent manner and decreased in parallel the
      expression of Wnt1, beta-catenin, c-Myc and cyclin D1, indicating that OCT might
      attenuate liver fibrosis, at least in part, by inhibiting Wnt/beta-catenin
      signaling pathway. Overall, these results provide a novel anti-fibrotic mechanism
      of OCT, which might be associated with its ability to repress Wnt/beta-catenin
      signaling pathway.

PMID- 30098498
TI  - Informal recycling, income generation and risk: Health and social harms among
      people who use drugs.
AB  - BACKGROUND: Informal recycling refers to the street-based collection of discarded
      materials for reuse, resale, or return to a recycling facility for money. While
      qualitative research has explored experiences and perceptions of informal
      recycling, little is known about the scope and exposures associated with informal
      recycling among people who use drugs (PWUD). METHODS: Using data from two
      prospective longitudinal cohorts of PWUD, we examined the prevalence of informal
      recycling and its association with social, structural and health risks, including
      criminal justice system involvement. RESULTS: Between June 2010 and May 2015, of
      1664 participants, 557 (33.5%) reported engaging in informal recycling during the
      study period. In multivariable generalised estimating equations (GEE) analyses,
      informal recycling was positively associated with injection drug use (Adjusted
      Odds Ratio (AOR) = 1.43, 95% Confidence Interval (CI) 1.21-1.68), public
      injection (AOR = 1.27, 95% CI 1.09-1.49), methamphetamine use (AOR = 1.35, 95% CI
      1.05-1.72), difficulty finding harm reduction equipment (AOR = 1.16, 95% CI 1.02
      1.32), and police interactions (AOR = 1.35, 95% CI 1.18-1.55). Sub-analyses
      revealed PWUD engaged in informal recycling were more likely to be told to move
      on, ticketed, stopped for jaywalking, and directed to services by police.
      CONCLUSIONS: These findings suggest informal recycling as a situated practice for
      PWUD, with potential indications for higher-risk drug use, experiencing greater
      surveillance, and difficulty accessing health and addiction treatment services.
      This research highlights the significance of the broader risk environment and the
      need for health-promoting policies for socioeconomically marginalised PWUD
      engaged in informal recycling.

PMID- 30098499
TI  - Altered transcallosal inhibition evidenced by transcranial magnetic stimulation
      highlights neurophysiological consequences of premature birth in early adulthood.
AB  - BACKGROUND AND OBJECTIVE: A very preterm birth can induce deleterious
      neurophysiological consequences beyond childhood; alterations of the corpus
      callosum (CC) are reported in adolescents born very preterm along with cognitive
      impairments. The question remains whether neurophysiological alterations are
      still detectable in adulthood such as an alteration in CC inhibitory function.
      The aim of the present study was thus to examine transcallosal inhibition in
      young adults born very preterm compared to counterparts born at term. STUDY
      PARTICIPANTS & METHODS: Transcallosal inhibition was probed by measuring the
      ipsilateral silent period (iSP) using transcranial magnetic stimulation (TMS) in
      13 young adults born at 33w of gestation or less (20 +/- 3. 2y) and 12 young
      adults born at term (22 +/- 1. 75y). Single high-intensity TMS were delivered to
      the primary motor cortex (M1) ipsilateral to the preactivated first dorsal
      interosseous (FDI) muscle. Occurrence, latency, and duration of iSP were measured
      in the FDI EMG activity, for both hemispheres alternatively (10-12 trials each)
      along with their resting motor threshold (RMT). RESULTS: In individuals born very
      preterm as compared to individuals born at term, ISP occurred less frequently (p
      < .0001), its latency was longer (p = .004), especially in the non-dominant
      hemisphere, its duration shorter (p < .0001), and RMT was higher in the non
      dominant M1 than in the dominant. CONCLUSIONS: Impairment of transcallosal
      inhibition along with asymmetry of M1 excitability in young adults born very
      preterm as compared to those born at term underline that neurophysiological
      consequences of a preterm birth can still be detected in early adulthood.

PMID- 30098500
TI  - Intravenous thrombolysis in stroke patients taking novel oral anticoagulants:
      experience with the low-dose 0.6 mg/kg of recombinant tissue-type plasminogen
      activator. Case reports.

PMID- 30098501
TI  - Modulation of P2X7 purinergic receptor activity by extracellular Zn2+ in cultured
      mouse hippocampal astroglia.
AB  - The P2X7R protein, a P2 type purinergic receptor functioning as a non-selective
      cation channel, is expressed in different cell types of the central nervous
      system in several regions of the brain. The activation of the P2X7R protein by
      ATP modulates excitatory neurotransmission and contributes to microglial
      activation, apoptosis and neuron-glia communication. Zinc is an essential
      micronutrient that is highly concentrated in the synaptic vesicles of
      glutamatergic hippocampal neurons where free zinc ions released into the synaptic
      cleft alter glutamatergic signal transmission. Changes in both P2X7R-mediated
      signaling and brain zinc homeostasis have been implicated in the pathogenesis of
      mood disorders. Here, we tested the hypothesis that extracellular zinc regulates
      P2X7R activity in the hippocampus. We observed that P2X7R is expressed in both
      neurons and glial cells in primary mouse hippocampal neuron-glia culture.
      Propidium iodide (PI) uptake through large pores formed by pannexins and P2X7R
      was dose-dependently inhibited by extracellular zinc ions. Calcium influx
      mediated by P2X7R in glial cells was also reduced by free zinc ions.
      Interestingly, no calcium influx was detected in response to ATP or 3'-O-(4
      Benzoyl) benzoyl ATP (BzATP) in neurons despite the expression of P2X7R at the
      plasma membrane. Our results show that free zinc ions can modulate hippocampal
      glial purinergic signaling, and changes in the activity of P2X7R may contribute
      to the development of depression-like behaviors associated with zinc deficiency.

PMID- 30098502
TI  - Increased attention to the tobacco power wall predicts increased smoking risk
      among adolescents.
AB  - The purpose of this correlational study was to evaluate the association between
      attention paid by adolescents to the tobacco power wall and their susceptibility
      to future smoking. The study was conducted in the RAND Store Lab (RSL), a life
      sized replica of a convenience store designed to investigate how tobacco
      advertising displays in retail point-of-sale environments relate to tobacco use
      risk and behaviors. In this study, middle and high school students (N = 80)
      shopped in the RSL while their attention to the tobacco power wall was measured
      covertly. Before and after shopping in the RSL, participants completed a measure
      of susceptibility to smoking in the future. Controlling for baseline cigarette
      smoking susceptibility and other potential confounders, attention toward the
      tobacco power wall was found to be significantly associated with future smoking
      susceptibility, p = .046. This finding suggests that policies aimed at decreasing
      the prominence of power walls in retail outlets should be given careful
      consideration as ways to reduce the impact of point-of-sale tobacco advertising
      and promotion on youth smoking susceptibility.

PMID- 30098503
TI  - Selection of Metastatic Breast Cancer Cell-Specific Aptamers for the Capture of
      CTCs with a Metastatic Phenotype by Cell-SELEX.
AB  - Circulating tumor cells (CTCs) have the potential to predict metastasis, and the
      capture of CTCs based on their surface markers is mostly applied for CTC
      detection. Considering that the CTCs with a metastatic phenotype preferably form
      a metastatic focus and that aptamers have the ability to bind targets with high
      specificity and affinity, we selected aptamers directed toward metastatic cells
      by subtractive Cell-SELEX technology using highly metastatic MDA-MB-231 cells as
      the target cell and low-metastatic MCF-7 cells as the negative cell for the
      capture of metastatic CTCs. Affinity and selectivity assays showed that aptamer
      M3 had the highest affinity, with a KD of 45.6 +/- 1.2 nM, and had good
      specificity against several other types of metastatic cancer cells. Based on
      these findings, we developed an M3-based capture system for CTC enrichment, which
      has the capability to specifically capture the metastatic cells MDA-MB-231 mixed
      with non-metastatic MCF-7 cells and CTCs derived from the peripheral blood from
      metastatic breast cancer patients. A further comparative analysis with the anti
      EpCAM probe showed that M3 probe captured epithelial feature-deletion metastatic
      cells. We developed an aptamer-based CTC capture system through the selection of
      aptamers by taking whole metastatic cells, not known molecules, as targets, which
      provided a new insight into CTC capture and Cell-SELEX application.

PMID- 30098505
TI  - Oxytetracycline effects in specific biochemical pathways of detoxification,
      neurotransmission and energy production in Oncorhynchus mykiss.
AB  - Oxytetracycline (OTC) is a tetracycline antibiotic, widely used in human and
      veterinary medicines, including in aquaculture. Given this use, OTC has been
      detected in different aquatic environments. Some recent works have demonstrated
      unintentional biological activity of OTC in non-target aquatic organisms. This
      study investigated the acute and chronic effects of OTC on the physiology of the
      fish species Oncorhynchus mykiss (rainbow trout), namely through the
      quantification of the activity of enzymes involved in different biochemical
      pathways, such as detoxification (phase II - glutathione S-transferases - GSTs,
      uridine-diphosphate-glucuronosyltransferases - UGTs), neurotransmission
      (acetylcholinesterase - AChE) and energy production (lactate dehydrogenase -
      LDH). The here-obtained data demonstrated the induction of GSTs activity in
      gills, and inhibition of AChE activity in eyes tissue, in chronically exposed
      organisms, as well as alterations in LDH activity following both exposures.
      Considering this set of results, we can infer that OTC exposure may have induced
      the glutathione pathway of detoxification in gills with the involvement of GSTs,
      or indirectly due to the metabolites that may have been produced. In turn, these
      metabolites may have interfered with the mechanism of neurotransmission, also
      causing physiological and biochemical disturbances in rainbow trout after OTC
      exposure, namely disturbances in energetic metabolism. In addition, it is
      important to stress that such occurrences took place at low, environmentally
      realistic levels of OTC, suggesting that organisms exposed in the wild may be
      putative targets of toxic effects by commonly used drugs such as antibiotics.

PMID- 30098504
TI  - Silencing of circRNA.2837 Plays a Protective Role in Sciatic Nerve Injury by
      Sponging the miR-34 Family via Regulating Neuronal Autophagy.
AB  - Circular RNAs (circRNAs) represent a class of non-coding RNAs that are involved
      in transcriptional and posttranscriptional gene expression regulation and
      associated with different kinds of human diseases. However, the characterization
      and function of circular RNAs in peripheral nerve injuries remain elusive. Here,
      we established a rat sciatic nerve injury model and identified at least 4,942
      distinct circular RNA candidates and a series of circular RNAs that were
      differentially expressed in injured nerve tissues compared with matched normal
      tissues. We characterized one frequently downregulated circular RNA,
      circRNA.2837, and further investigated its function in sciatic nerve injury. We
      found that circRNA.2837 regulated autophagy in neurons in vitro and in vivo, and
      downregulation of circRNA.2837 alleviated sciatic nerve injury via inducing
      autophagy in vivo. Mechanistically, knockdown of circRNA.2837 may protect neurons
      against neurological injury by acting as a sponge for members of miR-34 family.
      Our findings suggested that differentially expressed circular RNAs were involved
      in the pathogenesis of sciatic nerve injury, and circular RNAs exerted regulatory
      functions in sciatic nerve injury and might be used as potential targets in
      sciatic nerve injury therapy.

PMID- 30098506
TI  - Antimony enhances c-Myc stability in prostate cancer via activating CtBP2-ROCK1
      signaling pathway.
AB  - Antimony, one of the heavier pnictogens, is widely used in industry, and its
      toxicity has become a major concern. Although previous studies suggested that
      antimony might be a tumorigenic risk factor in several cancers, the molecular
      basis underlying antimony-mediated transformation remains unclear. Our results
      showed that the serum concentration of antimony was higher in prostate cancer
      specimens relative to that of benign prostate tissues, and this high serum
      concentration of antimony was closely associated with poorer outcome in prostate
      cancer patients. Additionally, we demonstrated that antimony could promote
      prostate cancer cell growth in vitro and in vivo. In order to gain insight into
      the potential mechanisms, we examined the effects of antimony exposure on
      downstream signaling that could contribute to tumor development. We found that
      low-dose antimony could regulate the expression of Ctbp2 by binding and
      regulating the activity of its MRE domain. Meanwhile, CtBP2 could
      transcriptionally regulate the expression of RhoC, which is a member of the
      RhoGTPase family. Subsequently, the kinase activity of ROCK1 is increased, which
      promotes the stability of oncogene c-Myc. Overall, our study demonstrated that
      antimony could enhance c-Myc protein stability and promote prostate cancer cell
      proliferation through activating CtBP2-ROCK1 signaling pathway. These findings
      also substantially highlighted the potential of targeting molecules within
      antimony induced CtBP2-c-Myc signaling pathway as a promising therapeutic
      approach for the treatment of prostate cancer.

PMID- 30098507
TI  - Leaf shape variation as a potential biomarker of soil pollution.
AB  - Halophytic plants play a fundamental role in salt marshes, influencing their
      structure, dynamics, and cycling of nutrients and minerals. These plants have the
      ability to retain metals in the soil, or absorb and retain them in underground
      structures, or transport them to their aerial structures. Here we aim to study
      shape variation in the leaves of Cressa truxillensis inhabiting the salt marsh of
      San Antonio Oeste, according to their proximity to a source of metals in the
      soil. A gradient of bioavailability of metal was observed in the soil, decreasing
      from the site closest to the source to the most distant point, where Zn was the
      most abundant metal followed by Pb and Cu. We used landmark-based geometric
      morphometric tools to study leaf shape variation. We observed more oval leaf
      growth on the farthest point of the pollutant's source, and lanceolate shape
      close to it. No significant among-site size differences were found. Collectively,
      these results suggest that the stress conditions associated with the soil metals'
      concentration generate changes in the leaf shape of Cressa truxilensis.
      Considering that this species has not been extensively analyzed, this study
      establishes a baseline and supports the use of the leaf as an early biomarker of
      stress by contamination in plants associated with marshes.

PMID- 30098508
TI  - Molybdenum and Cadmium exposure influences the concentration of trace elements in
      the digestive organs of Shaoxing duck (Anas platyrhyncha).
AB  - To investigate the toxic effects of Molybdenum (Mo) and Cadmium (Cd) on trace
      elements in digestive organs of Shaoxing duck (Anas platyrhyncha), 120 Shaoxing
      ducks were randomly divided into control group and 5 treatment groups which were
      treated with a commercial diet containing different dosages of Mo and Cd. On the
      60th and 120th days, the beak, esophagus, glandular stomach, muscular stomach,
      small intestine, large intestine and feces were collected to determine contents
      of Mo, Cd, copper (Cu), iron (Fe), zinc (Zn) and selenium (Se), then correlation
      analysis was performed. The results showed that Cd content in digestive organs
      significantly increased in co-treated groups compared to single treated groups
      and Mo concentration increased in Mo-treated groups compared to control group,
      whereas Cu, Fe, Zn and Se concentrations in digestive organs decreased in co
      treated groups. Furthermore, Cd and Mo were mainly accumulated in the small
      intestine and esophagus, respectively. There was a strongly positive correlation
      between Cd and Mo while they had negative correlation with Cu, Fe, Zn and Se,
      respectively. In feces, Mo and Fe contents in high dose of Mo group and high Mo
      combined with Cd group were significantly higher than those in control group, and
      Cu content in all treated groups significantly increased and Cd, Zn and Se
      concentrations had no difference. The results indicated that dietary Mo or/and Cd
      might disturb homeostasis of trace elements in digestive organs of Shaoxing duck.
      Moreover, the two elements presented a synergistic relationship.

PMID- 30098509
TI  - Synergistic toxicity of some sulfonamide mixtures on Daphnia magna.
AB  - In livestock farming, sulfonamides (SAs) are used prophylactically and
      simultaneously in large numbers of animals. Therefore, traces of these compounds,
      alone or in combination, have been repeatedly detected in the environment.
      Synergistic interactions among chemicals in such mixtures represent an area of
      concern for the regulatory authorities. In this study, the acute toxic effects of
      binary and ternary mixtures of SAs were evaluated in Daphnia magna, in order to
      verify whether, based on their individual toxicity, they jointly exert a larger
      effect than would be predicted by individual actions alone. First, following the
      Concentration Addition (CA) principle, some preliminary observations were made by
      testing a number of drug combinations with an expected 50% effect. Then, mixtures
      more recognised for their synergistic effect (four binary and two ternary) were
      assayed in a range of reducing concentrations. The data acquired were processed
      using CompuSyn software, which integrates the different shape of the curves
      obtained in calculating the Combination Index (CI) for the evaluation of
      synergistic effects. For binary mixtures, synergy was also evaluated using the
      curvilinear isobologram method for heterodynamic drugs. Results indicate that
      most of the selected mixtures exhibit a synergistic effect using the CI
      methodology. For binary mixtures, these findings were also confirmed by
      isobologram analysis. Detected synergies indicate that the CA is not always
      precautionary as a reference model for the evaluation of the aquatic toxicity of
      SAs mixtures.

PMID- 30098510
TI  - Complex effects of pollution on fish in major rivers in the Czech Republic.
AB  - Monitoring the contamination level in aquatic environments and assessing the
      impact on aquatic life occurs throughout the world. In the present study, an
      approach based on a combination of biomarkers and the distribution of various
      industrial and municipal pollutants was used to investigate the effect of aquatic
      environmental contamination on fish. Monitoring was performed in ten rivers in
      the Czech Republic (Berounka, Dyje, Elbe, Luznice, Odra, Ohre, Otava, Sazava,
      Svratka, and Vltava rivers, with one or two locations in each river) at the same
      sites that were regularly monitored within the Czech National Monitoring Program
      in 2007-2011. Health status, hepatic ethoxyresorufin-O-deethylase (EROD)
      activity, total cytochrome P450 content, and the plasma vitellogenin
      concentration were assessed in wild chub (Squalius cephalus) males caught at the
      monitored sites. The contamination level was the highest in the Svratka River
      downstream of Brno. Among all measured persistent organic pollutants (POPs),
      polychlorinated biphenyls and dichlorodiphenyltrichloroethane and its metabolites
      were the major contributors of POPs in fish muscle. Elbe, Odra, and Svratka
      rivers were identified as the most polluted. Fish from these locations showed
      reduced gonad size, increased vitellogenin concentration in male plasma, EROD,
      and total cytochrome P450 content. These biomarkers can be used for future
      environmental monitoring assessments. Overall, this study improves our
      understanding of the relationship between human activities and pollutant loads
      and further contributes to the decision to support local watershed managers to
      protect water quality in this region.

PMID- 30098511
TI  - Childhood maltreatment, pituitary volume and adolescent hypothalamic-pituitary
      adrenal axis - Evidence for a maltreatment-related attenuation.
AB  - BACKGROUND: Alterations of the development of the hypothalamic-pituitary-adrenal
      axis (HPAA) have been suggested to be related to experiences of early
      maltreatment. It has been postulated that early stress (i.e., maltreatment) leads
      to initial hyperactivation of the HPAA, which subsequently may progress to
      hypoactivation during the course of adolescence, however empirical studies on
      this hypothesis are rare. In the current study, we aimed to examine the
      longitudinal relationships between childhood maltreatment, early adolescent
      pituitary gland volume (PGV) and mid-adolescent cortisol output in an existing
      data set to explore the utility of PGV as a measure of HPAA function, and as an
      indirect test of the attenuation hypothesis. METHODS: The sample comprised 69
      adolescents (30 females), subsampled from a larger longitudinal, community-based
      study on adolescent development. PGV, as an estimate of chronic childhood HPAA
      activity, was measured by magnetic resonance imaging during early adolescence
      (mean age 12.62 +/- 0.45 years). Cortisol output was assessed via multiple
      salivary cortisol measures in mid-adolescence (mean age 15.52 +/- 0.39 years).
      The cortisol awakening response (CAR) was calculated as a measure of HPAA
      functioning. Retrospective assessment of childhood maltreatment was performed
      using the Childhood Trauma Questionnaire (CTQ). Regression analyses were
      conducted to examine whether childhood maltreatment, PGV, and their interaction,
      predicted mid-adolescent CAR. RESULTS: No main effect of PGV or maltreatment was
      found on adolescent CAR. PGV did however significantly interact with childhood
      maltreatment in predicting the CAR (t = -2.26; p = 0.024). Larger PGV positively
      predicted lower CAR in the context of relatively high childhood maltreatment (t =
      2.032; p = 0.046), but showed no relationship in the context of relatively low
      maltreatment (t = 0.723; p = 0.472). Maltreatment also interacted with sex, such
      that (only) in females, higher levels of maltreatment predicted a lower CAR (t = 
      2.04, p = 0.042). CONCLUSIONS: In the presence of childhood maltreatment, larger
      PGV was associated with lower CAR in adolescence, providing support for the
      application of PGV in studies of HPA axis function. Our finding is consistent
      with a maltreatment-related attenuation of HPAA functioning that may derive from
      a stress induced chronic hyperactivation during childhood. Prospective
      longitudinal studies are now required to further explicate these findings and
      relationships with psychopathology.

PMID- 30098512
TI  - Sleep quality is differentially related to adiposity in adults.
AB  - OBJECTIVES: Sleep duration is associated with adiposity in adults. Abdominal
      adiposity specifically is strongly correlated with metabolic alterations,
      however, the relationships between abdominal adiposity and sleep quality are
      incompletely understood. The purpose of this study is to test the hypothesis that
      abdominal adiposity is related to poor sleep quality while total adiposity is
      not; and to explore whether pathways, including immune system and hypothalamic
      pituitary-adrenal axis, link abdominal adiposity to poor sleep quality. METHODS:
      Subjects were 101 men and women aged 38.88 +/- 11.96 years with body mass index
      between 29.35 +/- 6.93 kg/m2. Subjective sleep quality was determined by the
      Pittsburgh Sleep Questionnaire Index (PSQI). Body composition was determined by
      dual energy X-ray absorptiometry. Saliva and blood samples were collected for
      assessment of cortisol and markers of inflammation. In a cross-sectional study
      design, correlation analysis was conducted to determine the relationships between
      poor sleep quality and adiposity. Participants were stratified based on PSQI
      score to evaluate differences in main outcomes between subjects with normal (NSQ;
      PSQI <= 5) vs poor sleep quality (PSQ; PSQI > 5). RESULTS: Poor sleep quality was
      related to greater visceral fat (r = 0.26; p < 0.05), but not total fat. The PSQ
      group had greater visceral fat compared to the NSQ group (1.11 +/- 0.83 kg vs
      0.79 +/- 0.62 kg; p < 0.05), however, there was no difference in total fat mass
      (33.18 +/- 14.21 kg vs 29.39 +/- 13.03 kg; p = 0.24). The PSQ group had
      significantly greater leptin (1.37 +/- 0.07 ng/ml vs 1.08 +/- 0.08 ng/ml; p <
      0.05), but hypothalamic-pituitary-adrenal axis activity did not differ between
      the PSQ and NSQ groups. CONCLUSIONS: Poor sleep quality is associated with
      greater visceral adiposity and leptin secretion. Further research is needed to
      probe potential cause and effect relationships among visceral adipose tissue,
      leptin, and sleep quality.

PMID- 30098514
TI  - Microvessel density and cell proliferation in juvenile ossifying fibroma: A
      comparative study with central ossifying fibroma.
AB  - Considered as an aggressive counterpart of central ossifying fibroma (OF),
      juvenile ossifying fibroma (JOF) is a benign fibro-osseous neoplasm characterized
      by an unpredictable destructive behavior, elevated morbidity, mutilating
      treatment and high potential for local recurrences. The aim of this study is to
      compare the analysis for cell proliferation and vascular markers between JOF and
      OF. Cell proliferation index was measured by Ki-67 and Mcm-2 expression and
      microvessel density (MVD) was obtained by the immunoexpression of CD34/CD105. We
      observed a reduced expression of vascular markers, where MVD for CD34 was
      significantly higher in JOF than in OF (p = 0.009), but no statistical difference
      was found for CD105. JOF and OF showed low expression for Ki-67 and Mcm-2 and no
      difference was noted between both, suggesting that other mechanisms such as anti
      apoptotic and/or pro-autophagic pathways or even increased expression of matrix
      metalloproteinases may be responsible for the aggressiveness of JOF.

PMID- 30098515
TI  - Clinicopathologic features of 300 rhabdomyosarcomas with emphasis upon
      differential expression of skeletal muscle specific markers in the various
      subtypes: A single institutional experience.
AB  - The present study was aimed at evaluating clinicopathologic and
      immunohistochemical (IHC) features of 300 rhabdomyosarcomas (RMSs), including
      differential IHC expression and prognostic value of myogenin and MyoD1 across
      various subtypes of RMSs. IHC expression of myogenin and MyoD1 was graded on the
      basis of percentage of tumor cells displaying positive intranuclear
      immunostaining i.e. grade 1 (1-25%); grade 2 (26-50%); grade 3 (51-76%) and grade
      4 (76-100%).Clinical follow-up was available in 238 (79.3%) patients. Various
      clinicopathologic parameters were correlated with 3-year disease free survival
      (DFS) and overall survival (OS). There were 140 cases (46.7%) of alveolar RMS
      (ARMS), 90 of embryonal RMS (ERMS) (30%), 61 (20.3%) of spindle cell/sclerosing
      RMS and 9 cases (3%) of pleomorphic RMS. Most cases, barring pleomorphic RMSs,
      occurred in the first two decades (228 cases) (76%), frequently in males, in the
      head and neck region (126) (42%). By immunohistochemistry, desmin was positive in
      292/299 (97.6%) tumors; myogenin in 238/267 (89.1%) and MyoD1 in 192/266 (72.2%)
      tumors. High myogenin expression (in >=51% positive tumor cells) was
      significantly associated with ARMSs (95/121, 78.5%), as compared to other
      subtypes (48/117, 41%) (p value < 0.001). High MyoD1 expression (>=51% tumor
      cells) was seen in more cases of pure sclerosing, combined with spindle
      cell/sclerosing RMSs (10/10, 100%), as compared to the other subtypes (91/141,
      67.4%) (p = 0.032). There was no significant difference between high myogenin
      expression and clinical outcomes. Patients without metastasis and harbouring
      tumors, measuring <=5 cm showed a significant increase in OS, with p values =
      0.01 and <0.001, respectively. ARMS was the most frequent subtype. There was a
      significant association between high myogenin expression and ARMSs and high MyoD1
      expression and spindle cell/sclerosing RMSs. High myogenin expression did not
      correlate with clinical outcomes. Patients with smaller sized tumors and without
      metastasis had significantly better clinical outcomes.

PMID- 30098513
TI  - Marital distress, depression, and a leaky gut: Translocation of bacterial
      endotoxin as a pathway to inflammation.
AB  - BACKGROUND: Marital distress and depression work in tandem to escalate risks for
      inflammation-related disorders. Translocation of bacterial endotoxin
      (lipopolysaccharide, LPS) from the gut microbiota to blood circulation stimulates
      systemic inflammatory responses. METHODS: To investigate increased gut
      permeability (a "leaky gut") as one potential mechanistic pathway from marital
      distress and depression to heightened inflammation, this secondary analysis of a
      double-blind, randomized crossover study examined serial assessments of two
      endotoxin biomarkers, LPS-binding protein (LBP) and soluble CD14 (sCD14), as well
      as C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor
      alpha (TNF-alpha) during two separate 9.5 h visits. The 43 (N = 86) healthy
      married couples, ages 24-61 (mean = 38.22), discussed a marital disagreement
      during both visits; behavioral coding of these interactions provided data on
      hostile marital behaviors, a hallmark of marital distress. The Structured
      Diagnostic Interview for DSM-IV assessed participants' mood disorder history.
      RESULTS: Participants with more hostile marital interactions had higher LBP than
      those who were less hostile. Additionally, the combination of more hostile
      marital interactions with a mood disorder history was associated with higher
      LBP/sCD14 ratios. Higher LBP and LBP/sCD14 were associated with greater CRP
      production; for example, only 21% of low LBP participants (lowest quartile) had
      average CRP across the day > 3, compared to 79% of those in the highest quartile.
      Higher sCD14 was associated with higher IL-6. CONCLUSIONS: These bacterial LPS
      translocation data illustrate how a distressed marriage and a mood disorder
      history can promote a proinflammatory milieu through increased gut permeability,
      thus fueling inflammation-related disorders.

PMID- 30098516
TI  - Influence of the material properties of a poly(D,L-lactide)/beta-tricalcium
      phosphate composite on the processability by selective laser sintering.
AB  - Complex 3D scaffolds with interconnected pores are a promising tool for bone
      regeneration. Such 3D scaffolds can be manufactured by selective laser sintering
      (SLS) from biodegradable composite powders. However, the mechanical strength of
      these scaffolds is often too low for medical application. We propose that the
      mechanical strength of laser-sintered scaffolds can be improved through composite
      powders with tailored properties (e.g., suitable powder particle size and melt
      viscosity for SLS). To prove this, two batches of a poly(D,L-lactide)
      (PDLLA)/beta-tricalcium phosphate (beta-TCP) composite powder with 50 wt% PDLLA
      and 50 wt% beta-TCP were synthesized. The two batches differed in polymer
      particle size, filler particle size, and polymer molecular weight. Both batches
      were processed with identical SLS process parameters to study the extent to which
      the material properties influence how well a PDLLA/beta-TCP (50/50) composite can
      be processed with SLS. In the SLS process, batch 2 showed improved melting
      behavior due to its smaller polymer particle size (approx. 35 um vs. 50 um) and
      its lower zero-shear melt viscosity (5800 Pa?s vs. 17,900 Pa?s). The better
      melting behavior of batch 2 led to SLS test specimens with lower porosity
      compared to batch 1. In consequence, the batch 2 specimens exhibited a larger
      biaxial bending strength (62 MPa) than the batch 1 specimens did (23 MPa). We
      conclude that a tailored composite powder with optimized polymer particle size,
      filler particle size, and polymer molecular weight can increase the achievable
      mechanical strength of laser-sintered scaffolds.

PMID- 30098517
TI  - Understanding perceptions of nursing professional identity in students entering
      an Australian undergraduate nursing degree.
AB  - Developing a professional identity is an essential transition for nursing
      students as they move through their undergraduate degree. Professional identity
      is described as a person's perception of themselves within a profession or the
      collective identity of the profession. The formation of a professional identity
      is an evolving process, shaped by the media, educational experiences and role
      modelling. The aim of this study was to develop a greater understanding of the
      perceptions that students, about to embark on their undergraduate nursing degree,
      had of the nursing profession. A drawing and mind mapping exercise was conducted
      with a convenience sample of commencing nursing students to explore how they
      viewed their future profession. The data underwent thematic analysis and then
      grouped into sub-themes and themes. Four key themes were identified, 'To be a
      nurse, I have to look the part', 'To be a nurse, I have to perform in a variety
      of roles', 'To be a nurse, I have to connect with others', and 'To be a nurse, I
      have to care for myself.' The formation of a strong pre-professional identity is
      important for nursing students due to the link between future job satisfaction
      and the development of a robust nursing workforce.

PMID- 30098518
TI  - IRF4 in multiple myeloma-Biology, disease and therapeutic target.
AB  - Multiple Myeloma (MM) is an incurable hematologic malignancy characterized by
      abnormal proliferation of plasma cells. Interferon Regulatory Factor 4 (IRF4), a
      member of the interferon regulatory family of transcription factors, is central
      to the genesis of MM. IRF4 is highly expressed in B cells and plasma cells where
      it plays essential roles in controlling B cell to plasma cell differentiation and
      immunoglobulin class switching. Overexpression of IRF4 is found in MM patients'
      derived cells, often as a result of activating mutations or translocations, where
      it is required for their survival. In this review, we first describe the roles of
      IRF4 in B cells and plasma cells and then analyse the subversion of the IRF4
      transcriptional network in MM. Moreover, we discuss current therapies for MM as
      well as direct targeting of IRF4 as a potential new therapeutic strategy.

PMID- 30098519
TI  - Comparison of three bullet recovery systems.
AB  - Comparing the marks left on questioned bullets to those left on reference bullets
      is the main aim of a firearm identification expertise. Thus, producing reference
      bullets with a questioned firearm is an essential step. Different kinds of system
      have been developed to safely recover bullets fired from questioned firearms.
      However, the performance of each system and its impact on traces left on the
      bullets have not been addressed. Three bullet recovery systems - a horizontal
      water tank, a cotton tube and a recently designed fleece - were used to fire
      seven types of ammunition of various type, shape and casing. The bullets were
      then described and images of their surface were acquired with an automatic system
      to study the impact of each system on the bullets. The water tank is the more
      efficient system in terms of quality of the marks. However, it cannot be used to
      fire every type of ammunition. Some of them, such those used by law enforcement,
      tend to be damaged with this system. A way to mitigate the problem is to use the
      cotton or the fleece-based systems, the latter being more universal. It requires
      a cleaning step to remove all the fibres from the surface of the bullet, but the
      marks left by the weapon are still of interest.

PMID- 30098520
TI  - Femtosecond laser pulse assisted photoporation for drug delivery in Chronic
      myelogenous leukemia cells.
AB  - Chronic myelogenous leukemia (CML) is a myeloproliferative disorder occurs in the
      pluripotent hematopoietic stem cell. Currently, first-generation tyrosine kinase
      inhibitor (TKI) imatinib is the mainstay for the treatment of CML. Second
      generation TKI's like ponatinib, dasatinib, nilotinib, and bafetinib were treated
      against resistant CML. However, several CML patients develop resistance towards
      all existing inhibitors. Curcumin (Curcuma longa) a plant-derived natural
      compound is an effective bioactive component against various cancers including
      CML. Many studies have shown that curcumin induces time- and dose-dependent
      apoptosis in CML cells by regulating various downstream molecular regulators.
      Despite curcumin's selective cytotoxicity towards cancer cells, it has very poor
      bioavailability both in in-vitro and in-vivo conditions. In this present study,
      we have used femtosecond laser (fs-laser) pulses to ablate the cell membrane and
      standardized the conditions required for creating a cell membrane pores with less
      lethality. Following fs-laser pulse irradiation, K562 cells were incubated along
      with curcumin 30 MUM for 0 h, 6 h,12 h and 24 h. Interestingly irradiated cells
      have shown higher sensitivity towards curcumin than non-irradiated cells.
      Immunoblotting studies showed higher induction levels of cleaved caspase 3 and 9
      in irradiated population than non-irradiated. In summary, the results prove that
      irradiation by fs-laser pulses enhanced the bioavailability of curcumin and shows
      caspase-mediated cell death in irradiated CML cells than other populations.

PMID- 30098522
TI  - Synthesis, X-ray structure, DFT and antimicrobial studies of Ag(I) complexes with
      nicotinic acid derivatives.
AB  - The [Ag(Menic)2(ClO4)]2, (1) and [Ag(NA)2]ClO4, (2) complexes, where Menic;
      methylnicotinate and NA; nicotinamide, were synthesized and characterized using
      elemental analysis, FTIR, NMR and single crystal X-ray diffraction combined with
      DFT calculations. The Ag(I) is coordinated with two organic ligand molecules in
      both complexes. In 1, the coordination sphere is completed by one ClO4- anion as
      a monodentate ligand while in 2, the ClO4- anion is in the outer sphere. Both
      complexes showed some argentophilic interactions where the AgAg distance is
      shorter in 1 (3.152(6) A) than 2 (3.303(9) A). The organic ligands showed no
      antimicrobial activity up to 15 mmole/L while both silver(I) complexes are
      biologically active against different bacterial strains and the fungus Candida
      albicans. The minimal inhibition concentrations (MICs) of the Ag(I) complexes are
      in the range of 4-8 mmol/L depending on the nature of microorganism. Complex 2
      showed slightly better antifungal action than 1. In contrast, complex 1 showed
      higher antibacterial potency against P. aeruginosa, C. perfringens, Sh. sonnei
      and Str. pneumonia compared to 2. The antibacterial action of 2 is slightly
      higher or equal against the rest of microorganisms compared to 1. The strength
      and nature of the AgAg, AgN and Ag...O interactions were analyzed using atoms in
      molecules and natural bond orbital calculations.

PMID- 30098523
TI  - Infants perceive two-dimensional shape from horizontal disparity.
AB  - Previous studies observed that responsiveness to horizontal disparity as such
      emerges at approximately 2 months of age. Moreover, 3- to 4-month-old infants
      utilize stereoscopic information to perceive object variations in depth. The
      present study investigated infants' ability to respond to crossed horizontal
      disparity information that defines two-dimensional shape. Infants 4 and 5 months
      of age were habituated to either a cross or the outline of a square. During the
      posthabituation period, they were presented with both shapes. The stimuli were
      dynamic random dot stereograms shown on an autostereoscopic monitor. The
      participants 5 but not 4 months of age displayed significant novelty preferences
      for the unfamiliar shape during the posthabituation period. Five-month-old
      infants are hence sensitive to horizontal disparity information that specifies
      shape.

PMID- 30098521
TI  - Mitochondrial dynamics (fission and fusion) and collagen production in a rat
      model of diabetic wound healing treated by photobiomodulation: comparison of 904
      nm laser and 850 nm light-emitting diode (LED).
AB  - OBJECTIVE: Mitochondrial dysfunction has been associated with the development of
      diabetes mellitus which is characterized by disorders of collagen production and
      impaired wound healing. This study analyzed the effects of photobiomodulation
      (PBM) mediated by laser and light-emitting diode (LED) on the production and
      organization of collagen fibers in an excisional wound in an animal model of
      diabetes, and the correlation with inflammation and mitochondrial dynamics.
      METHODS: Twenty Wistar rats were randomized into 4 groups of 5 animals. Groups:
      (SHAM) a control non-diabetic wounded group with no treatment; (DC) a diabetic
      wounded group with no treatment; (DLASER) a diabetic wounded group irradiated by
      904 nm pulsed laser (40 mW, 9500 Hz, 1 min, 2.4 J); (DLED) a diabetic wounded
      group irradiated by continuous wave LED 850 nm (48 mW, 22 s, 1.0 J). Diabetes was
      induced by injection with streptozotocin (70 mg/kg). PBM was carried out daily
      for 5 days followed by sacrifice and tissue removal. RESULTS: Collagen fibers in
      diabetic wounded skin were increased by DLASER but not by DLED. Both groups
      showed increased blood vessels by atomic force microscopy. Vascular endothelial
      growth factor (VEGF) was higher and cyclooxygenase (COX2) was lower in the DLED
      group. Mitochondrial fusion was higher and mitochondrial fusion was lower in DLED
      compared to DLASER. CONCLUSION: Differences observed between DLASER and DLED may
      be due to the pulsed laser and CW LED, and to the higher dose of laser.
      Regulation of mitochondrial homeostasis may be an important mechanism for PBM
      effects in diabetes.

PMID- 30098524
TI  - Age-sex specific and sequela-specific disability-adjusted life years (DALYs) due
      to dental caries preventable through water fluoridation: An assessment at the
      national and subnational levels in Iran, 2016.
AB  - We assessed disability-adjusted life years (DALYs) due to dental caries
      preventable through water fluoridation apportioned by sex, age group, sequela,
      province, and community type in Iran, 2016. The burden of disease due to dental
      caries was extracted from the Global Burden of Disease Study 2016 (GBD 2016) and
      the caries preventive effect of water fluoridation was calculated using a
      database of fluoride levels in drinking water. All the preventable DALYs were
      caused by years lived with disability (YLDs) because of the non-fatal character
      of dental caries. DALYs and DALY rate (per 100,000 people) preventable through
      water fluoridation at the national level in 2016 were 14,971 (95% uncertainty
      interval 7348- 24,725) and 18.73 (9.19-30.93), respectively. The national
      population preventable fraction (PPF) of dental caries by water fluoridation was
      determined to be as high as 0.176 (0.141-0.189). The share of sequelae in the
      preventable DALYs at the national level were estimated to be 76.8% for edentulism
      and severe tooth loss, 21.4% for caries of permanent teeth, and 1.8% for caries
      of deciduous teeth. The national DALYs and DALY rate preventable through water
      fluoridation exhibited no difference by sex, but considerably increased by age
      from 110 (37-223) and 1.5 (0.5-3.1) for the age group 0-4 y to 4331 (2334-6579)
      and 88.9 (47.9-135.1) for the age group 65 y and older, respectively. Over 80% of
      the national preventable DALYs occurred in urban areas due to higher population
      and lower coverage of fluoridated drinking water. The highest provincial DALYs
      and DALY rate preventable by water fluoridation were observed in Tehran and Gilan
      to be 3776 (1866-6206) and 37.2 (18.6-60.8), respectively. The results indicated
      that water fluoridation can play a profound role in the promotion of dental
      public health and compensate the spatial inequality and increasing temporal trend
      of health losses from dental caries at the national level.

PMID- 30098525
TI  - Socioeconomic and particulate air pollution correlates of heart disease risk.
AB  - How does risk of heart disease depend on age, sex, smoking, income, education,
      marital status, and outdoor concentrations of fine particulate matter (PM2.5)? We
      join data available from the Centers for Disease Control and Prevention (CDC)
      Behavioral Risk Factor Surveillance (BRFSS) System for years 2008-2012 to US
      Environmental Protection Agency (EPA) data on county-specific concentrations of
      fine particulate matter (PM2.5) to quantify associations among these variables
      and to explore possible causal interpretations. Low income is identified as a
      direct cause of increased heart disease risk in this data set. The effect depends
      on age and sex: it is most pronounced for men under age 70 and for women under
      age 80. Income is significantly associated with all of the other variables
      examined and confounds the association between PM2.5 and heart disease risk. This
      association is significant in regression models that exclude income, but not in
      regression models that include it, both in the data set as a whole and in the
      subset of observations with PM2.5 < 15 MUg/m3. Causal directed acyclic graph
      (DAG) models and non-parametric model ensemble partial dependence plots confirm
      that higher incomes reduce heart disease risk, consistent with previous
      observations of socioeconomic gradients in health risks. They support
      interpretation of this as a robust causal relation apparent in non-parametric
      analyses, and hence independent of any specific parametric modeling assumptions.

PMID- 30098526
TI  - Axillary artery and brachial plexus injury secondary to proximal humeral
      fractures: A report of 2 cases.
AB  - INTRODUCTION: Axillary artery and brachial plexus injuries have been reported to
      be associated with proximal humeral fractures. In this report, we present two
      cases of axillary artery and brachial plexus injury secondary to proximal humeral
      fracture. PRESENTATION OF CASES: Case 1: An 88-year-old woman with cognitive
      impairment slipped and fell at home. The diagnosis was left proximal humeral
      fracture. The second day, paralysis of left upper arm due to left axillary artery
      occlusion appeared. Axillary-brachial artery bypass surgery was performed. After
      that, a radial artery pulse was palpable. Ten months have passed since the
      operation, but the neurologic deficit has not been restored. Case 2: A 74-year
      old woman fell from a ladder. She was diagnosed with a right proximal humeral
      fracture and right axillary artery occlusion. Emergency axillary-brachial bypass
      surgery and osteosynthesis were performed. After reestablishing the blood flow,
      there have been no signs of blood flow disorders but paralysis has remained.
      DISCUSSION: In neither of the two cases, were obvious findings of brachial plexus
      injury detected during surgery. The delayed onset of motor palsy implied that an
      ischemic factor was implicated in case 1. The acute onset of motor palsy might
      have been caused by a mechanical factor such as the dislocated of humeral head in
      case 2. CONCLUSION: Axillary artery and brachial plexus injury secondary to
      proximal humeral fracture is rare but it can develop severe sequels. By
      identifying the high-risk patients, diagnosis and management of this vascular and
      plexus injury might lead to improvement.

PMID- 30098527
TI  - The challenge of synthetic biology. Synthetic Darwinism and the aperiodic crystal
      structure.
AB  - 'Grand Challenges' offer ways to discover flaws in existing theory without first
      needing to guess what those flaws are. Our grand challenge here is to reproduce
      the Darwinism of terran biology, but on molecular platforms different from
      standard DNA. Access to Darwinism distinguishes the living from the non-living
      state. However, theory suggests that any biopolymer able to support Darwinism
      must (a) be able to form Schrodinger's 'aperiodic crystal', where different
      molecular components pack into a single crystal lattice, and (b) have a
      polyelectrolyte backbone. In 1953, the descriptive biology of Watson and Crick
      suggested DNA met Schrodinger's criertion, forming a linear crystal with
      geometrically similar building blocks supported on a polyelectrolye backbone. At
      the center of genetics were nucleobase pairs that fit into that crystal lattice
      by having both size complementarity and hydrogen bonding complementarity to
      enforce a constant geometry. This review covers experiments that show that by
      adhering to these two structural rules, the aperiodic crystal structure is
      maintained in DNA having 6 (or more) components. Further, this molecular system
      is shown to support Darwinism. Together with a deeper understanding of the role
      played in crystal formation by the poly-charged backbone and the intervening
      scaffolding, these results define how we might search for Darwinism, and
      therefore life, on Mars, Europa, Enceladus, and other watery lagoons in our Solar
      System.

PMID- 30098528
TI  - Sorption of organic compounds to two diesel soot black carbons in water evaluated
      by liquid chromatography and polyparameter linear solvation energy relationship.
AB  - Substantial variability in sorption capacity of black carbon (BC) has been a
      major challenge for accurate fate and risk assessment of organic pollutants in
      soils and sediments. 16 model organic sorbates (logKOW = 0.38-4.21) encompassing
      diverse chemical functionalities were used to probe the sorption capacity of two
      diesel soot samples representative of graphitic BC (BC1, specific surface area
      (SSA) = 87 m2/g) and amorphous, oxygenated BC (BC2; SSA = 3.6 m2/g). The BC-water
      sorption coefficients (logKBC) of the model sorbates were determined using
      reversed-phase liquid chromatography (RP-LC) on soot-filled columns. It was found
      that mass-based logKBC's of BC1 (1.64-3.66 L/kgBC) exceeded those of BC2 (0.68
      3.48 L/kgBC) consistently for all model sorbates. However, area-normalized
      logKBC's of BC2 were larger than those of BC1, suggesting that the overall
      sorption was more favored on the oxygenated sorbent per area basis. Linear
      solvation energy relationships (LSERs) for sorption onto BC1 and BC2 were found
      to be logKBC = (2.49 +/- 0.65)E + (-2.71 +/- 0.88)S + (1.17 +/- 0.46)A + (2.52 +/
      0.34)V and logKBC = (1.12 +/- 0.39)E + (-1.68 +/- 0.32)S + (-3.70 +/- 0.57)B +
      (4.37 +/- 0.38)V + (-1.51 +/- 0.22), respectively. The LSERs indicated that
      sorption onto soot was generally enhanced with increasing non-specific van der
      Waals and decreasing cavitation cost (i.e., eE, sS, and vV terms). The logKBC
      difference between BC1 and BC2, DeltalogKBC, appeared to be correlated with the H
      bonding capacity of the sorbates but not logKOW. Analysis of literature and
      experimental logKBC's revealed that logKBC and logSSA across different types of
      BC (i.e., soot, char, charcoal, activated carbon) were linearly correlated for
      benzene and toluene (r2 = 0.88-0.91). This work illustrates the utility of RP-LC
      in determining the sorption coefficients of high-capacity sorbents and suggests
      the possibility of a unified sorption model for the continuum of black carbon.

PMID- 30098529
TI  - Semi-continuous pharmaceutical and human tracer monitoring by POCIS sampling at
      the watershed-scale in an agricultural rural headwater river.
AB  - Pharmaceutical monitoring (37 pharmaceuticals and 3 human tracers) was conducted
      in a headwater streams in southwest France, an area characterized by a low
      population density with an elderly population (30% > 60 years old) and extensive
      agriculture (cow cattle breeding). Polar Organic Chemical Integrative Sampler
      (POCIS) were exposed for 14-day consecutive periods in 2016 at three sampling
      points. Three human wastewater tracers and 20 pharmaceuticals commonly used for
      human and/or cattle were quantified in headwaters. Succession of small Wastewater
      Treatment Plant (WWTP), non-collective sanitation, discharges of untreated
      effluents as well as the river ability to dilute discharged wastewater, mainly
      explain the pharmaceuticals and human tracers concentrations. Pharmaceutical
      loads were time-dependent and were higher during cold season due to increase of
      pharmaceutical consumption. In contrast, better degradation and/or sorption onto
      river biofilms in warm season induced the decrease of headwater pharmaceutical
      content. The headwaters streams were contaminated by compounds found in other
      type of watershed, but beta-blocker were the compounds quantified in higher
      concentration with frequencies of 100%, which was consistent with the elderly
      population living in the watershed. Specific compounds (sulfamerazine and
      sulfamethoxazole) used to cattle medical care were detected in waters, but at a
      low content.

PMID- 30098530
TI  - Remediation of soil polluted with HMW-PAHs by alfalfa or brome in combination
      with fungi and starch.
AB  - High-molecular weight polycyclic aromatic hydrocarbons (HMW-PAHs) are common
      pollutants in soil of coal mining areas that affect the safety of crops and the
      environment. In a pot experiment, we compared the remediation potential of
      alfalfa (Medicago sativa Linn) and brome (Bromus inermis Leyss.) either alone or
      in combination with starch or Fusarium sp. strain ZH-H2 for a farmland soil
      contaminated with 4-6-ring PAHs from a coal mine area. The alfalfa and brome
      alone treatments reduced the concentrations of most HMW-PAHs. However, when
      starch was added, the removal rates of indeno(1,2,3-cd)pyrene and
      benzo(ghi)perylene were significantly higher for brome than for alfalfa. When ZH
      H2 was combined with brome, benzo(k)fluoranthene, benzo(a)pyrene, indeno(1,2,3
      cd)pyrene, and benzo(ghi)perylene degradation rates were significantly enhanced
      compared with brome alone. In contrast, an antagonistic effect was observed
      between alfalfa and Fusarium. The brome, starch and ZH-H2 combination resulted in
      far better removal rates than the alfalfa combination. Maximum removal rates were
      obtained with the brome + starch + ZH-H2 combination for benzo(k)fluoranthene
      (42.64%), benzo(a)pyrene (51.01%), indeno(1,2,3-cd)pyrene (62.29%), and
      benzo(ghi)perylene (74.85%). These removal rates were 829.78%, 182.34%, 46.13%,
      and 70.94% higher than the equivalent alfalfa combination treatments. The lignin
      peroxidase activity was significantly increased in the presence of starch, ZH-H2
      and brome, consistent with the increased removal rates of HMW-PAHs.

PMID- 30098531
TI  - Fabrication of a loose nanofiltration candidate from Polyacrylonitrile/Graphene
      oxide hybrid membrane via thermally induced phase separation.
AB  - It is still a challenge to design and fabricate a robust nanoporous membrane in
      large scale and of fundamental importance for practical application. Here, a
      robust three/two-dimensional polyacrylonitrile/graphene oxide (PAN/GO)
      homogeneous nanoporous membrane is fabricated in large scale via thermally
      induced phase separation method, which guarantees the membrane with high
      mechanical strength and selective separation properties. Differing from
      conventional nanofiltration (NF) membrane with high rejection to both salt and
      dye, the resulting hybrid membrane is relative loose, which shows outstanding
      performances, i.e. high dye rejection and low salt rejection, high permeability
      and antifouling properties, acting as a promising candidate for dye/salt
      fractionation. The incorporation of 0.2 wt% GO endows membrane with excellent
      performance, where high tensile strength, high water permeability (33 L? m-2? h
      1? bar-1), selectivity (100% to methyl blue, 99.8% to acid red 18, 26.7% to
      magnesium sulfate and 10.9% to sodium chloride and flux recovery ratio of 84.4%)
      are perfectly balanced. Its homogeneous structure and high strength guarantee
      long term use without the peeling of thin active layer as encountered by
      conventional NF membranes. The successful fabrication of such a hybrid membrane
      provides an attractive opportunity for loose NF membrane preparation with
      performance enhancement in a feasible way for practical application.

PMID- 30098532
TI  - Toxicity of enzymatically decolored textile dyes solution by horseradish
      peroxidase.
AB  - The oxidative systems including enzymatic systems have been widely studied as an
      alternative for textile effluents treatment. However, studies have shown that
      some oxidative processes can produce degradation products with higher toxicity
      than the untreated dye. In this work, enzymatic dye decolorization was evaluated
      by horseradish peroxidase enzyme (HRP) and the toxicity of discoloration products
      was evaluate against Daphnia magna, Euglena gracilis algae, and Vibrio fischeri.
      Dye decolorization kinetics data were evaluated and the pseudo-second-order model
      showed the best-fitting to the experimental data. In addition, it was observed an
      increased acute and chronic toxicity associated with the decolorization
      efficiency. The Reactive Blue 19 and Reactive Black dye showed the highest
      toxicity against D. Magna (16 toxicity factor) and V. Fischeri (32 toxicity
      factor) after enzymatic decolorization. For the chronic toxicity against D.
      Magna, Reactive Red was the only dye with no fertility inhibition. In relation to
      toxicity tests with E. gracilis algae, it was not observed photosynthetic
      inhibition for all dyes. This study verified the viability of the enzyme
      horseradish peroxidase in the textile dyes decolorization and the importance to
      evaluate the decolorization products.

PMID- 30098533
TI  - Liquid-liquid phase-change absorption of SO2 using N, N-dimethylcyclohexylamine
      as absorbent and liquid paraffin as solvent.
AB  - In the present work, liquid-liquid phase-change absorption of SO2 was
      investigated using N, N-dimethylcyclohexylamine (DMCHA) as an absorbent, and high
      boiling liquid paraffin (LP) as a solvent to reduce volatilization of the
      absorbent. The homogenous solution was split into two immiscible phases upon SO2
      loading. The phase-change mechanism was attributed to the polarity variation of
      DMCHA before and after absorption by forming the charge-transfer complex
      DMCHA.SO2. The viscosity of the lower phase reached a maximum value of 24.5 mPa s
      at the absorption capacity of 1 mol SO2/mol DMCHA, and the viscosity of the
      corresponding upper phase was 46.4 mPa s. Both are lower than the reported
      viscosity of most ionic liquids. This solution exhibited extremely high mass
      selectivity of SO2/CO2 with a value of 626. The mass absorption capacity was
      founded to be 1.19 g SO2/g DMCHA at 1 atm, which is comparable with the highest
      reported mass absorption capacity. At low partial pressure, the absorption
      capacity still reached 0.78 g/g at 0.1 atm, 0.43 g/g at 0.02 atm and 0.27 g/g at
      0.001 atm. Furthermore, DMCHA could be completely regenerated in 10 min via
      microwave heating. All the results indicated this phase-change solution is a
      promising candidate for SO2 capture.

PMID- 30098534
TI  - Polystyrene microplastics alter the behavior, energy reserve and nutritional
      composition of marine jacopever (Sebastes schlegelii).
AB  - Uptake and toxicity of microplastics on marine organisms have been reported
      elsewhere. However, there is limited knowledge regarding the ecological effects
      of microplastics on marine organisms. In this study, we investigated the effects
      of polystyrene microplastics (1 * 106 microspheres per L) on the behavior, energy
      reserve and nutritional composition of juvenile jacopever (Sebastes schlegelii).
      Compared to the controls, fish treated by microplastics showed lower sensitivity
      toward the added food in the tank, and increased foraging time, indicating that
      microplastics significantly weakened feeding activity of the fish. Interestingly,
      the microplastics treated-fish obviously reduced swimming speed and range of
      movement, demonstrating that polystyrene microplastics could have negative effect
      on hunting behavior. Furthermore, polystyrene microplastics accumulated in the
      gills and intestine, causing significant histopathological changes in the
      gallbladder and liver. Moreover, the energy reserve and nutritional quality of
      fish were influenced by microplastics as evidenced by lower growth, protein and
      lipid contents. Our results highlighted the potential negative effects of
      microplastics on marine ecological function and food safety.

PMID- 30098535
TI  - Linalool bioactive properties and potential applicability in drug delivery
      systems.
AB  - The medicinal properties of essential oils from aromatic plants are known since
      antiquity. Currently, the technological innovation enabled the reinvention of the
      ancient plant knowledge leading to the identification and extraction of organic
      compounds present in essential oils. These organic compounds belong mainly to the
      terpene group and are accountable for the wide range of bioactive properties
      attributed to essential oils. Linalool (C10H18O), so-called 3,7-dimethyl-1,6
      octadien-3-ol, is a monoterpene alcohol broadly present as a major constituent of
      plant essential oils, particularly lavender and coriander. Linalool per se is non
      toxic and, according to recent in vitro and in vivo scientific studies, it has
      demonstrated to have a comprehensive range of bioactive properties, which can be
      exploited for pharmaceutic and cosmetic applications. The present review focuses
      on the anti-inflammatory, anticancer, anti-hyperlipidemic, antimicrobial,
      antinoceptive, analgesic, anxiolytic, antidepressive and neuroprotective
      properties of linalool. The advantages of the loading in nanotechnology-based
      drug delivery systems, with the purpose of enhancing its bioactive properties are
      also discussed.

PMID- 30098536
TI  - A rational and iterative process for targeted nanoparticle design and validation.
AB  - The lack of understanding of fundamental nano-bio interactions, and difficulties
      in designing particles stable in complex biological environments are major
      limitations to their translation into biomedical clinical applications. Here we
      present a multi-parametric approach to fully characterize targeted nanoparticles,
      and emphasizes the significant effect that each detail in the synthetic process
      can have on downstream in vitro results. Through an iterative process, particles
      were designed, synthesized and tested for physico-chemical and bio-interactive
      properties which allowed the optimization of nanoparticle functionality. Taken
      together all interative steps demonstrate that we have synthesized a
      multifunctional gold nanoparticles that can detect ERBB2-positive breast cancer
      cells while showing stealth-like behavior toward ERBB2-negative cells and
      excellent physicochemical stability.

PMID- 30098537
TI  - Coacervation of resilin fusion proteins containing terminal functionalities.
AB  - Liquid-liquid phase transition known as coacervation of resilin-like-peptide
      fusion proteins containing different terminal domains were investigated. Two
      different modular proteins were designed and produced and their behavior were
      compared to a resilin-like-peptide without terminal domains. The size of the
      particle-like coacervates was modulated by the protein concentration, pH and
      temperature. The morphology and three-dimensional (3D) structural details of the
      coacervate particles were investigated by cryogenic transmission electron
      microscopy (cryo-TEM) and tomography (cryo-ET) reconstruction. Selective adhesion
      of the coacervates on cellulose and graphene surfaces was demonstrated.

PMID- 30098538
TI  - Mobility of traffic-related Pd and Pt species in soils evaluated by sequential
      extraction.
AB  - The aim of this study was to evaluate the mobility of platinum (Pt) and palladium
      (Pd) emissions from automotive catalysts in soils and to contribute to the risk
      assessment of platinum group metals (PGMs) discharged from catalysts in the
      environment. To address this question, for the first time risk assessment code
      (RAC) was applied to consider the results from sequential extraction of different
      Pd and Pt species from soils. For this purpose, model soil samples were prepared
      spiking defined Pd or Pt species, respectively, at known concentrations. In order
      to mimic emitted species as well as possible transformation products of traffic
      related Pd and Pt emissions in soils, coated and uncoated elemental nanoparticles
      (cPd/cPt NPs, Pd/Pt NPs) and ionic divalent metal species (Pd(II)/Pt(II)) were
      applied. All model samples were characterized in detail and the developed
      sequential extraction scheme was validated. RAC values ranged between 24 and 8%
      revealing medium to low risk. The order of mobility for the studied species was
      found to be Pt(II) > cPd NPs " Pd(II) > Pd NPs > Pt NPs > cPt NPs. Furthermore,
      migration of Pd species in gravity columns was studied confirming highest
      transport of cPd NPs.

PMID- 30098539
TI  - Contamination, potential mobility, and origins of lead in sediment cores from the
      Shima River, south China.
AB  - Identifying contamination sources of environmental media and revealing their
      changing trends over time is useful for regional contamination control and
      environmental improvements. Four sediment cores (S1-S4) were collected from the
      Shima River to determine lead (Pb) concentrations, geochemical fractions and
      isotopic compositions, as well as the geochronology of core S3. The results show
      that Pb concentrations decreased from the upper and middle reach sites (means:
      57.6, 95.9, and 97.6 mg kg-1, respectively) to the lower reach site (43.8 mg kg
      1), resulting in a minimal to moderate enrichment in the sediments; enrichment
      increased due to anthropogenic Pb inputs at the river middle reach site since the
      1990s. Sediment Pb in the geochemical fractions followed a decreasing order of
      reducible (47.3%) > residual (37.8%) > oxidizable (11.2%) > acid-soluble fraction
      (3.68%), exhibiting high mobility, further verifying the anthropogenic inputs. A
      descending trend in the 206Pb/207Pb ratio of the top sediments was the result of
      anthropogenic activities. In the present study, coal combustion, which was the
      major anthropogenic Pb source determined by its isotopic composition, contributed
      significantly (means: 18.4-60.6%) to sediment Pb based on a three end-members
      model. Less of a contribution (0-10.6%) was derived from vehicle exhaust. The
      increasing trend in the coal contribution was in accordance with that of the coal
      consumption in the study area. These results suggest that Pb contamination
      resulting from coal combustion has grown to become a major environmental issue in
      the study area.

PMID- 30098540
TI  - Multibiomarker interactions to diagnose and follow-up chronic exposure of a
      marine crustacean to Hazardous and Noxious Substances (HNS).
AB  - Integrated compensatory responses of physiological systems towards homeostasis
      are generally overlooked when it comes to analysing alterations in biochemical
      parameters indicative of such processes. Here an hypothesis-driven multivariate
      analysis accounting for interactive multibiomarker responses was used to
      investigate effects of long-term exposure of Carcinus maenas to Hazardous and
      Noxious Substances (HNS). Adult male crabs were exposed to low and high post
      spill levels of acrylonitrile (ACN) or aniline (ANL) for 21d. Bioaccumulation,
      feeding behaviour, and biomarkers related to mode-of-action (MoA)
      (detoxification, neurotransmission and energy production) were evaluated over
      time. Distinct temporal patterns of response to low and high exposure
      concentrations were depicted, with a main set of interactive multibiomarker
      predictors identified for each HNS (five for ACN and three for ANL), useful to
      follow coupled evolvement of biomarker responses. ACN caused peripheral
      neurotoxic effects coupled with enhanced biotransformation and significant
      oxidative damage particularly relevant in gills. ANL elicited alterations in
      central neurotransmission affecting ventilation coupled with very low levels of
      oxidative damage in gills. Results indicate chronic toxicity data are determinant
      to improve HNS hazard assessment if the aim is to obtain reliable risk
      calculations, and develop effective predictive models avoiding overestimation but
      sufficiently protective. Accounting for multibiomarker interactions brought
      otherwise overlooked information about C. maenas responses and MoA of ACN and
      ANL.

PMID- 30098541
TI  - Development and preliminary validation of a brief behavioral measure of psychotic
      propensity.
AB  - Extensive research demonstrates that the dimensional assessment of psychotic
      manifestations is a primary strength of the Rorschach inkblot task, which
      provides an in vivo sample of problem-solving behavior and normative standards
      concerning the logic and coherence of thought processes and the typicality of
      perceptual representations. This article presents foundational research for the
      Thought and Perception Assessment System (TPAS), a Rorschach-based system
      designed to assess solely for disordered thinking and perceptual aberrations
      using either the standard 10-card set of inkblots or alternative 3-, 4-, and 5
      card short forms. Using data from three patient samples (ns = 61, 93, and 133)
      and one nonpatient sample (n = 118), we document the equivalence of mean scores
      across the full and short-form card sets. We also document satisfactory
      interrater reliability and validity for the full and short forms, as well as
      strong part-whole reliability coefficients between the short forms and the full
      form. Consistent with psychometric theory and the principle of aggregation, each
      type of coefficient decreased as a function of decreasing the number of cards. We
      discuss implications and future applications in research and clinical assessment.

PMID- 30098542
TI  - Maladaptive personality traits in patients identified at lower-risk and higher
      risk for psychosis.
AB  - The 'at-risk' state for psychosis is a high-risk paradigm that examines factors
      that contribute to conversion to a first episode of psychosis. Although a
      multitude of contributing factors have been identified in one's susceptibility to
      conversion to psychosis, dimensional pathological personality traits have not
      been examined in 'at-risk' populations. In this study we examine lower- versus
      higher-risk for psychosis using traits from the DSM-5 Alternative Dimensional
      Model of Personality Disorders (AMPD) to investigate which AMPD personality
      traits distinguish those 'at-risk' patients at relatively lower-risk for
      conversion to psychosis versus those at higher-risk. Remitted schizophrenic
      patients served as the comparison group. MANOVA analyses revealed significant
      group differences on the PID-5, with the higher-risk patients scoring higher on
      two of the five AMPD trait domains - Negative Affectivity and Detachment -
      compared to lower-risk patients. Maladaptive personality traits from the AMPD may
      serve as potential risk factor for conversion to psychosis.

PMID- 30098543
TI  - The relationship between night eating symptoms and disordered eating attitudes
      via insomnia and chronotype differences.
AB  - Humans' sleep timing and the psychological construct "diurnal preference"
      determines their "chronotype" (i.e., morning or evening type). Diurnal
      preferences can affect sleep-awake rhythms and eating behaviors. Our aim in this
      study was to examine the relationship between night eating symptoms and
      disordered eating attitudes by evaluating insomnia and chronotype differences in
      university students. The participants, 383 university students, filled out a
      package of psychological tools, including the Morningness-Eveningness
      Questionnaire, the Insomnia Severity Index, the Night Eating Questionnaire, and
      the Eating Attitude Test. One way analysis of variance was used to investigate
      the relationship of chronotypes with scale scores, and mediation regression
      analysis was used to investigate the indirect effects of night eating symptoms on
      disordered eating attitudes. Insomnia and night eating scores of the participants
      varied statistically according to chronotypes, and both insomnia and night eating
      scores were associated with the evening type. Findings show that night eating
      symptoms have a direct effect on the chronotype differences and insomnia and an
      indirect effect on disordered eating attitudes, by increasing insomnia scores. In
      conclusion, night eating syndrome may represent the misalignment of food intake
      and may shift the circadian rhythm to delayed sleep phase, acting as a peripheral
      oscillator in human.

PMID- 30098544
TI  - Oxytocin improves animal behaviors and ameliorates oxidative stress and
      inflammation in autistic mice.
AB  - OBJECTIVE: Autism is a neurodevelopmental disorder which significantly impacts
      the quality of people's life. Oxytocin is a hormone impacting the social
      cognition and interpersonal trust. In this study, we aimed to explore the role of
      oxytocin in autism. METHODS: Autistic mice models were established by valproate.
      Animal behaviors were assessed by open field test, tail suspension test, marble
      burying test and three-chamber social interaction test. Oxidative stress was
      evaluated by the levels or activities of malondialdehyde, superoxide dismutase,
      glutathion peroxidase, reduced glutathione and reactive oxygen species.
      Inflammation was assessed by the levels of tumor necrosis factor-alpha,
      interleukin-1beta and interleukin-6. The number of activated microglia was
      detected by immunofluorescence with an Iba-1 antibody. RESULTS: Our results
      showed that oxytocin improved the behaviors of autistic mice, with less anxiety,
      depression and repetitive behavior, and ameliorated social interaction. Further
      study showed that the elevated oxidative stress and inflammation in autistic mice
      were alleviated after treatment of oxytocin. CONCLUSION: Our study demonstrates
      that oxytocin treatment ameliorates autism in a mouse model, maybe through its
      modulation on oxidative stress and inflammation. It is indicated that oxytocin
      may beneficial to autism.

PMID- 30098545
TI  - LINC01116 targets miR-520a-3p and affects IL6R to promote the proliferation and
      migration of osteosarcoma cells through the Jak-stat signaling pathway.
AB  - OBJECTIVE: The purpose of this study was to find out the important lncRNA-miRNA
      mRNA axis and pathway in osteosarcoma (OS) through bioinformatics analysis and
      verify the biological functions of lncRNA/miRNA/mRNA in OS through in vitro and
      in vivo assays. METHODS: The differential expression mRNAs and lncRNAs were
      identified through microarray analysis, and the altered pathways were identified
      by GSEA. The Pearson Coefficient was used to analyze the correlations between
      mRNAs and lncRNAs. Kaplan-Meier survival analysis was preformed using patient
      information in GEO database. Their target miRNAs were predicted by Targetscan and
      miRanda database and confirmed by dual luciferase reporter assay. QRT-PCR were
      utilized to detected the relative expressions of mRNAs, miRNAs and lncRNAs. The
      expressions of IL6R protein and pathway related proteins were detected by western
      blot. OS cell viability, migration and apoptosis were determined through MTT
      assay, Transwell assay and flow cytometry. Tumor formation in nude mice verified
      the influence of LINC01116 in vivo. RESULTS: The Jak-stat signaling pathway was
      activated in OS tissues. LINC01116 expression was positively correlated with IL6R
      expression. MiR-520a-3p targeted the 3'-UTR of LINC01116 and IL6R. Lower
      expression levels of miR-520a-3p significantly correlated with shorter survival
      of patients. LINC01116 and IL6R were up-regulated while miR-520a-3p was down
      regulated in OS. LINC01116 and IL6R promoted the viability and migration of OS
      cells, while miR-520a-3p acted as a tumor suppressor. MiR-520a-3p inhibitor could
      rescue the suppressive effects of si-LINC011116 and si-IL6R on OS development.
      The Jak-stat signaling pathway related proteins were also down-regulated by miR
      520a-3p. Down-regulation of LINC01116 inhibited the tumor growth in nude mice.
      CONCLUSION: LINC01116 up-regulated IL6R in OS through targeting miR-520a-3p, thus
      activating the Jak-stat signaling pathway and promoting the progression of OS.

PMID- 30098546
TI  - Salicornia ramosissima J. Woods seeds affected the normal regenerative function
      on carbon tetrachloride-induced liver and kidney injury.
AB  - The growing importance of Salicornia plants as bioactive agents and health
      promoters associated with the continuous demand for alternative treatments for
      liver disorders, has stimulated us to evaluate the renal and hepatic effects of
      S. ramosissima seeds in mice under normal conditions and exposure to toxic
      products as carbon tetrachloride (CCl4). Thus, histopathological and lipid
      peroxidation evaluations of the liver and kidneys were performed. Powdered dried
      seeds of S. ramosissima (SRS) were administered orally for 22 days at a dose of
      2000 mg/kg/day to male mice in three different settings: 1) seed effects, 2)
      protection against CCl4 acute toxicity (0.2 mL/kg) and 3) regeneration after
      acute exposure to CCl4 (0.2 mL/kg), each study being performed with appropriate
      control animals. Mice treated with SRS per se had slightly enlarged hepatic
      sinusoids and noticeable renal inflammation. SRS did not show effective
      protection against mice exposed to CCl4 and had no positive influence on liver
      and kidney recovery after CCl4 administration. These results demonstrated that
      SRS failed to improve hepato- and nephrotoxicity, in addition to the apparent
      synergism between CCl4 and SRS under these experimental conditions. Although the
      biological mechanisms of S. ramosissima are not fully understood, the evidence
      suggests further research to elucidate its adverse biological effects.

PMID- 30098547
TI  - Allyl methyl sulfide, an organosulfur compound alleviates hyperglycemia mediated
      hepatic oxidative stress and inflammation in streptozotocin - induced
      experimental rats.
AB  - Therapeutic approaches based on dietary compounds obtained from food products to
      handle diabetes involving oxidative stress and inflammation. Garlic is a common
      spice and has a long history as a folk remedy. Allyl methyl sulfide (AMS) is a
      potential garlic-derived organosulfur compound displaying a substantial range of
      optimistic actions in various diseases. Herein, we investigated the potential
      role of AMS in ameliorating the effects of oxidative stress and inflammation in
      the liver of streptozotocin (STZ)-induced experimental rats. Diabetes was induced
      by single intraperitoneal (i.p.) injection of STZ (40 mg/kg/b.w). STZ-induced
      hyperglycemic rats received daily intragastric doses of 50, 100 and 200 mg/kg/b.w
      of the AMS for 30 days. Dietary intervention of AMS (100 mg/kg b.w) resulted in
      significant attenuation in blood glucose and expression of pro-inflammatory
      markers TNF-alpha, IL-6, NF-kappaB p65 unit and significant elevation in the
      plasma insulin level. Moreover, AMS instigated a marked enhance in the levels of
      hepatic tissue non enzymatic antioxidants and the activities enzymatic
      antioxidants of diabetic rats with significant decline in lipid peroxides and
      hydroperoxides formation, serum biomarkers of liver damage, thus representing the
      protecting efficacy of AMS in hyperglycemic state. The pathological abnormalities
      in hepatic tissues of diabetic rats were significantly ameliorated by AMS
      supplementation and offered great support to the biochemical findings. These
      conclusions explicate the prospective use of AMS as a promising compound against
      glucotoxicity mediated hepatic oxidative dysfunction in rats. Clinical trials in
      validating this benefit for optimizing the AMS nutrition are however warranted.

PMID- 30098548
TI  - Asiaticoside counteracts the in vitro activation of microglia and astrocytes:
      Innuendo for multiple sclerosis.
AB  - BACKGROUND: During the development of Multiple Sclerosis (MS) there is a marked
      activation of microglia and astrocyte, leading to progressive inflammation and
      degeneration of myelin sheath which results in axonal loss and neuron damage.
      PURPOSE: In this study, we have explored the action of Asiaticoside A against the
      activated microglia and astrocytes. METHODS: Primary microglia and astrocyte
      cultures were used for the study and the activity were evaluated using cell
      proliferation assay, nitrate assay and TNFalpha estimation using ELISA. RESULTS:
      Asiaticoside A inhibited the production of nitric oxide and TNFalpha in LPS
      activated primary microglia and astrocyte cultures. CONCLUSION: This study
      suggests that Asiaticoside A may be effective against the progression of MS.

PMID- 30098549
TI  - Chronic hyperglycemia mediated physiological alteration and metabolic distortion
      leads to organ dysfunction, infection, cancer progression and other
      pathophysiological consequences: An update on glucose toxicity.
AB  - Chronic exposure of glucose rich environment creates several physiological and
      pathophysiological changes. There are several pathways by which hyperglycemia
      exacerbate its toxic effect on cells, tissues and organ systems. Hyperglycemia
      can induce oxidative stress, upsurge polyol pathway, activate protein kinase C
      (PKC), enhance hexosamine biosynthetic pathway (HBP), promote the formation of
      advanced glycation end-products (AGEs) and finally alters gene expressions.
      Prolonged hyperglycemic condition leads to severe diabetic condition by damaging
      the pancreatic beta-cell and inducing insulin resistance. Numerous complications
      have been associated with diabetes, thus it has become a major health issue in
      the 21st century and has received serious attention. Dysregulation in the
      cardiovascular and reproductive systems along with nephropathy, retinopathy,
      neuropathy, diabetic foot ulcer may arise in the advanced stages of diabetes.
      High glucose level also encourages proliferation of cancer cells, development of
      osteoarthritis and potentiates a suitable environment for infections. This review
      culminates how elevated glucose level carries out its toxicity in cells,
      metabolic distortion along with organ dysfunction and elucidates the
      complications associated with chronic hyperglycemia.

PMID- 30098550
TI  - Standardized Ginkgo biloba extract EGb 761(r) attenuates early brain injury
      following subarachnoid hemorrhage via suppressing neuronal apoptosis through the
      activation of Akt signaling.
AB  - BACKGROUND: Early brain injury (EBI) plays a critical role in determining the
      outcome of subarachnoid hemorrhage (SAH). The present study was designed to
      investigate the role of EGb 761, a standardized extract of Ginkgo biloba, in SAH
      induced EBI and to explore its potential mechanism of action. METHOD: A rat SAH
      model was established by the endovascular perforation process. Doses of 10, 50
      and 100 mg/kg EGb 761 were injected intraperitoneally 2 h after SAH was induced.
      Mortality, SAH grade, neurological score and brain water content were measured 24
      h after SAH was induced. A Western blot assay was performed to assess the
      expression of the apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, Akt
      and phosphorylated Akt (p-Akt). Terminal deoxynucleotidyl transferase-mediated
      dUTP nick end labeling (TUNEL) and neuronal nuclei (NeuN) double
      immunofluorescence staining were used to detect apoptotic neurons. RESULTS:
      Animals suffered from serious neurological deficits and increased brain water
      content after induction of SAH. Rats treated with EGb 761 experienced dose
      dependent attenuation of neurological dysfunction and decreased brain water
      content. In addition, EGb 761 significantly activated Akt signaling accompanied
      by increased Bcl-2 levels and decreased expression of Bax and cleaved caspase-3.
      Moreover, EGb 761 decreased the number of TUNEL/NeuN-positive cells in a dose
      dependent manner. However, all the beneficial effects of EGb 761 for SAH were
      abolished by the Akt inhibitor MK2206. CONCLUSION: Our results indicated that EGb
      761 could ameliorate SAH-induced EBI and that the neuroprotective effects of EGb
      761 against SAH were exerted via suppression of neuronal apoptosis through
      activation of the Akt pathway.

PMID- 30098551
TI  - Long non-coding RNA TUG1 sponges miR-197 to enhance cisplatin sensitivity in
      triple negative breast cancer.
AB  - Breast cancer is the leading cause of women death worldwide. Several long non
      coding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressors
      during the progression of cancers. However, the role of taurine upregulated gene
      (TUG1) in mediating the chemotherapy sensitivity of triple negative breast cancer
      (TNBC) has not been studied yet. In TNBC patients, we observed a significant
      decrease of TUG1 in tumor tissues compared to the normal tissues. Similarly, TUG1
      expression was significantly decreased in TNBC cell lines compared with normal
      breast epithelial cell line and cell lines of other subtypes of breast cancer. In
      MDA-MB-231 and BT549, cisplatin induced cell growth arrest was remarkably
      augmented by overexpression of TUG1 and was significantly reduced by TUG1
      silencing. Moreover, very low concentration of cisplatin caused cell
      proliferation inhibition in TUG1-overexpressed-TNBC cells. In addition, we found
      that TUG1 negatively regulated miR-197 expression in the tested TNBC cell lines.
      Sponging of TUG1 to miR-197 was proved by a dual luciferase reporter assay. We
      further predicted and validated that nemo-like kinase (NLK), which was positively
      controlled by TUG1, was a target gene of miR-197. Via regulation of miR-197/NLK,
      TUG1 inactivated WNT signaling pathway and thus increasing chemotherapy
      sensitivity of TNBC cells. Analysis of TCGA database showed that higher
      expression of TUG1 was associated with better prognosis in breast cancer
      patients. Our current study drew a preliminary conclusion that TUG1 was involved
      in chemotherapy sensitivity in TNBC cells.

PMID- 30098552
TI  - Asymmetrical flow field-flow fractionation in purification of an enveloped
      bacteriophage phi6.
AB  - Basic and applied virus research requires specimens that are purified to high
      homogeneity. Thus, there is much interest in the efficient production and
      purification of viruses and their subassemblies. Advances in the production steps
      have shifted the bottle neck of the process to the purification. Nonetheless, the
      development of purification techniques for different viruses is challenging due
      to the complex biological nature of the infected cell cultures as well as the
      biophysical and -chemical differences in the virus particles. We used
      bacteriophage phi6 as a model virus in our attempts to provide a new purification
      method for enveloped viruses. We compared asymmetrical flow field-flow
      fractionation (AF4)-based virus purification method to the well-established
      ultracentrifugation-based purification of phi6. In addition, binding of phi6
      virions to monolithic anion exchange columns was tested to evaluate their
      applicability in concentrating the AF4 purified specimens. Our results show that
      AF4 enables one-hour purification of infectious enveloped viruses with specific
      infectivity of ~1 * 1013 PFU/mg of protein and ~65-95% yields. Obtained purity
      was comparable with that obtained using ultracentrifugation, but the yields from
      AF4 purification were 2-3-fold higher. Importantly, high quality virus
      preparations could be obtained directly from crude cell lysates. Furthermore,
      when used in combination with in-line light scattering detectors, AF4
      purification could be coupled to simultaneous quality control of obtained virus
      specimen.

PMID- 30098553
TI  - The effects of transport mode use on self-perceived health, mental health, and
      social contact measures: A cross-sectional and longitudinal study.
AB  - BACKGROUND: Transport mode choice has been associated with different health risks
      and benefits depending on which transport mode is used. We aimed to evaluate the
      association between different transport modes use and several health and social
      contact measures. METHODS: We based our analyses on the Physical Activity through
      Sustainable Transport Approaches (PASTA) longitudinal study, conducted over a
      period of two years in seven European cities. 8802 participants finished the
      baseline questionnaire, and 3567 answered the final questionnaire. Participants
      were 18 years of age or older (16 years of age or older in Zurich) and lived,
      worked and/or studied in one of the case-study cities. Associations between
      transport mode use and health/social contact measures were estimated using mixed
      effects logistic regression models, linear regression models, and logistic
      regression models according to the data available. All the associations were
      assessed with single and multiple transport mode models. All models were adjusted
      for potential confounders. RESULTS: In multiple transport mode models, bicycle
      use was associated with good self-perceived health [OR (CI 95%) = 1.07 (1.05,
      1.08)], all the mental health measures [perceived stress: coef (CI 95%) = -0.016
      (-0.028, -0.004); mental health: coef (CI 95%) = 0.11 (0.05, 0.18); vitality:
      coef (CI 95%) = 0.14 (0.07, 0.22)], and with fewer feelings of loneliness [coef
      (CI 95%) = -0.03 (-0.05, -0.01)]. Walking was associated with good self-perceived
      health [OR (CI 95%) = 1.02 (1.00, 1.03)], higher vitality [coef (CI 95%) = 0.14
      (0.05, 0.23)], and more frequent contact with friends/family [OR (CI 95%) = 1.03
      (1.00, 1.05)]. Car use was associated with fewer feelings of loneliness [coef (CI
      95%) = -0.04 (-0.06, -0.02)]. The results for e-bike and public transport use
      were non-significant, and the results for motorbike use were inconclusive.
      CONCLUSIONS: Similarity of findings across cities suggested that active
      transport, especially bicycle use, should be encouraged to improve population
      health and social outcomes.

PMID- 30098554
TI  - History, advancements, and perspective of biological research in deep-underground
      laboratories: A brief review.
AB  - The world is entering a new era of exploring and exploiting the deep-underground
      space. With humans poised to reach historical depths in the use of the deep
      Earth, it is essential to understand the effect of the deep-underground
      environment on the health of humans and other living organisms. This article
      outlines the history and development of biological research conducted in deep
      underground laboratories and provides insight into future areas of investigation.
      Many deep-underground laboratories have investigated the effects of reduced
      cosmic ray muons flux, searching for rare events such as proton decay, dark
      matter particles, or neutrino interactions, but few have focused on the influence
      of the environmental factors in the deep-underground on living organisms. Some
      studies revealed that prokaryote and eukaryote cells maintained in low levels of
      background radiation exhibited an stress response, which manifested as changes in
      cell growth, enzyme activity, and sensitivity to factors that cause genetic
      damage; however, the underlying mechanisms are unclear. There remains an urgent
      need to understand the detrimental and beneficial biological effects of low
      background radiation and other factors in the deep-underground on humans and
      other organisms. Consequently, a multidisciplinary approach to medical research
      in the deep-underground has been proposed, creating a new discipline, deep
      underground medicine, and representing a historical milestone for exploring the
      deep Earth and in medical research.

PMID- 30098555
TI  - Simultaneous removal of nitrogen and phosphorus by magnesium-modified calcium
      silicate core-shell material in water.
AB  - In this study, a new core-shell material (CMCS) is prepared with magnesium oxide
      (MgO) around calcium silicate hydrate (CSH), and CSH is prepared by SiO2 from the
      red mud. The CMCS simultaneously removes ammonia nitrogen (NH4+) and phosphate
      (PO43-) by chemical precipitation and it can achieve recovery of nitrogen and
      phosphorus. The removal process of NH4+ and PO43- is as follows. First, the shell
      of MgO is used to remove NH4+ and a part of the PO43- by the assisted adsorption
      and struvite (MgNH4PO4.6H2O) precipitation method. Then the CSH is used to remove
      the residual part of PO43- by chemical precipitation (Ca5(PO4)3OH, CaHPO4 and
      Ca3(PO4)2). Furthermore, the MgO shell of CMCS not only removes NH4+ and PO43-,
      but also can control the calcium ions (Ca2+) spill from CSH and pH in the process
      of removing NH4+ and PO43-. The removal rate of NH4+ and PO43- can reach 76.63%
      and 87.18%, respectively, in the solution in 80 min, but in the actual wastewater
      the removal rate of NH4+ and PO43- is 61.40% and 62.83%, respectively. Finally,
      CMCS was recycled five times and its removal rates of NH4+ and PO43- are 21.01%
      and 24.99%, respectively. The aim of this article is to present CMCS, which has a
      good effect on removing the NH4+ and PO43- simultaneously.

PMID- 30098556
TI  - Functional and structural biomarkers to monitor heavy metal pollution of one of
      the most contaminated freshwater sites in Southern Europe.
AB  - This study evaluated the biological effects of highly polluted freshwater
      environment (Regi Lagni channels, S Italy) on the aquatic moss Leptodictyum
      riparium, exposed in bags at three sites representative of different
      environmental conditions and characterized by different heavy metal burdens.
      Bioaccumulation, ultrastructural alterations, Reactive Oxygen Species (ROS)
      production, antioxidant enzymes activity and DNA damage were assessed. To better
      evaluate the biological response of the moss species to heavy metals, the same
      biological parameters were assessed also in L. riparium samples cultured in vitro
      using metal mixtures at the same concentrations as measured at the 3 field
      exposure sites. Heavy metals were accumulated into the moss tissues causing
      severe ultra-structural damages at higher concentration case studies, and the ROS
      production as well as the activity of the enzyme followed a concentration
      dependent increase. However, the DNA damage trend suggested a threshold effect
      that changed between field and in vitro experiment. The enrichment factor
      suggests that the concentration in the most polluted site is close to the upper
      limit of L. riparium to accumulate metals. Overall, combining measures of the
      morpho-functional traits at different level contribute to improving the knowledge
      about the tolerance of L. riparium to heavy metal stress, suggesting that this
      moss could be suitable for biomonitoring activity in field conditions.

PMID- 30098557
TI  - Non-targeted metabolomics reveals alterations in liver and plasma of gilt-head
      bream exposed to oxybenzone.
AB  - The extensive use of the organic UV filter oxybenzone has led to its ubiquitous
      occurrence in the aquatic environment, causing an ecotoxicological risk to biota.
      Although some studies reported adverse effects, such as reproductive toxicity,
      further research needs to be done in order to assess its molecular effects and
      mechanism of action. Therefore, in the present work, we investigated metabolic
      perturbations in juvenile gilt-head bream (Sparus aurata) exposed over 14 days
      via the water to oxybenzone (50 mg/L). The non-targeted analysis of brain, liver
      and plasma extracts was performed by means of UHPLC-qOrbitrap MS in positive and
      negative modes with both C18 and HILIC separation. Although there was no
      mortality or alterations in general physiological parameters during the
      experiment, and the metabolic profile of brain was not affected, the results of
      this study showed that oxybenzone could perturb both liver and plasma metabolome.
      The pathway enrichment suggested that different pathways in lipid metabolism
      (fatty acid elongation, alpha-linolenic acid metabolism, biosynthesis of
      unsaturated fatty acids and fatty acid metabolism) were significantly altered, as
      well as metabolites involved in phenylalanine and tyrosine metabolism. Overall,
      these changes are signs of possible oxidative stress and energy metabolism
      modification. Therefore, this research indicates that oxybenzone has adverse
      effects beyond the commonly studied hormonal activity, and demonstrates the
      sensitivity of metabolomics to assess molecular-level effects of emerging
      contaminants.

PMID- 30098558
TI  - Efficiency and surface characterization of different plant derived biochar for
      cadmium (Cd) mobility, bioaccessibility and bioavailability to Chinese cabbage in
      highly contaminated soil.
AB  - Cadmium (Cd) contamination in red soil has become a serious environmental concern
      due to its toxic effects on organisms and the food chain. Possible eco-friendly
      solutions for Cd immobilization were required to reduce its mobility through
      biochar. This study evaluated the comparative efficiency of rice straw (RSB),
      rice hull (RHB) and maize stover (MSB) derived biochar (BC) on Cd mobility and
      its accumulation in Chinese cabbage (Brassica chinensis L.), which is highly Cd
      accumulating crop. Results showed that the soil chemical properties (pH, organic
      carbon and nutrients) significantly increased with increasing the biochar
      application rate from 1.5% to 3%. Concentration of Cd decreased in CaCl2 extract
      by 58.6, 39.7 and 46.49% and in toxicity characteristics leaching test (TCLP) by
      42.9, 32.7 and 36.7% for RSB, RHB and MSB, respectively at 3% application rate.
      The simple bioaccessibility extraction test (SBET) techniques showed a
      significant decrease in Cd by 30.5, 20.6 and 27.5% for RSB, RHB and MSB,
      respectively at the 3% application rate. Moreover, the Cd contents in the cabbage
      shoots decreased by 25, 21.3 and 23.1% for RSB, RHB and MSB at a 3% application
      rate and in the roots by 31.3, 23.9 and 26.5% for RSB, RHB and MSB at a 3%
      application rate, respectively. Bioaccumulation (BCF) and translocation factors
      (TF) were significantly decreased upto 26.5% and 11%, respectively among all
      biochar types. Overall, RSB demonstrated positive results as soil amendments for
      Cd immobilization and thereby, reducing its bioavailability in the Cd
      contaminated soil to mitigate food security risks.

PMID- 30098559
TI  - The aryl hydrocarbon receptor (AhR) activity and DNA-damaging effects of
      chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs).
AB  - An increasing number of studies have indicated that environmental contamination
      with chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) has been
      underestimated. However, insufficient available toxicological information on Cl
      PAHs makes evaluating their risks to health challenging. Two in vitro bioassays
      were used in the present study to characterize the aryl hydrocarbon receptor
      (AhR) activity and DNA-damaging effects of 22 low-molecular-weight PAHs and their
      Cl-PAHs by using the EROD assay in rat hepatoma (H4IIE) cells and the SOS/umu
      test (S. typhimurium TA1535/pSK1002). Compared with their parent PAHs, most of
      the Cl-PAHs enhanced AhR-mediated activity in the EROD assay. 1,3,6,8-Tetrachloro
      pyrene (1,3,6,8-Tetracl-Py) induced the greatest potency of EROD activity (83.1%
      TCDD-max) and its single point ReP was 6.64 * 10-6. Compared with their parent
      PAHs, several Cl-PAHs showed significant DNA-damaging effects in the SOS/umu test
      with the addition of S9, and the toxic equivalency of benzo[a]pyrene (TEQBaP) was
      calculated for them. 9-Chloroanthracene (9-Ant) and 5,6-Dichloroacenaphthene (5,6
      Dicl-Ace) had relatively high TEQBaP (0.62 and 0.54, respectively). However, only
      1,3,6,8-Tetracl-Py elicited strong DNA-damaging effects in the absence of S9. The
      degree of chlorination, the position of chlorine substitutions, and the structure
      of parent PAHs influenced the potency of low-molecular-weight PAHs with regard to
      their AhR activity and DNA-damaging effects. More concern should be raised for
      these environmentally relevant pollutants.

PMID- 30098560
TI  - Impact on growth, oxidative stress, and apoptosis-related gene transcription of
      zebrafish after exposure to low concentration of arsenite.
AB  - Low concentrations of arsenic (As) contamination in aquatic environment is a
      worldwide issue, which is of great concern. To evaluate the impact of low
      concentrations of As on zebrafish, we measured the growth, antioxidant enzymes
      including superoxide dismutase (SOD) and catalase (CAT), oxidative damage
      (malondialdehyde, MDA) and apoptosis-related genes (nrf2, p53 and c-jun) of adult
      zebrafish after exposing to different AsIII concentrations (0, 10, 50, 100 or 150
      MUg L-1) for 28 d. Results indicated that exposure to low AsIII concentrations
      decreased the zebrafish weight by 14%, increased the activities of SOD and CAT by
      23-41% and 31-59%, decreased the contents of MDA by 29-54%, and modulated
      transcription of apoptosis related genes. Our study showed that chronic exposure
      to AsIII concentrations <150 MUg L-1 generated oxidative stress and damage on
      zebrafish, and altered apoptosis-related genes in zebrafish.

PMID- 30098561
TI  - Bioremediation of hexavalent chromium by endophytic fungi; safe and improved
      production of Lactuca sativa L.
AB  - One of the main problems of the industrialized world is the accumulation of
      chromium (Cr) in soil, which is a serious threat to the crops. Complete removal
      of Cr from the contaminated soils poses a great challenge. However, this issue
      can be minimised by using plant growth promoting microbes as a bioremediation
      tool. In the present study, healthy plants established near the University campus
      in Mardan were selected for the isolation of Cr resistant endophytes. From the
      designated plants, 114 species of endophytic fungi were isolated. Among the 114
      isolated strains, 4 strains have induced resistance in L. sativa against Cr. The
      strains were identified as Aspergillus fumigatus, Rhizopus sp., Penicillium
      radicum and Fusarium proliferatum based on ITS region (18 S rDNA) homology. The
      isolates have removed Cr from soil and culture media as well as bio-transformed
      it from highly toxic hexavalent to least toxic trivalent form, thus helped the Cr
      stressed L. sativa to restore its normal growth. The Rhizopus Sp. CUC23 has
      mainly accrued Cr and detoxified intracellularly, whereas A. fumigatus ML43 and
      P. radicum PL17 has detoxified up to 95% of Cr extracellularly. From the results,
      it is concluded that the selected endophytic strains might be used as
      biofertilizer for healthy and safe crop production in Cr contaminated soils.

PMID- 30098562
TI  - Mercury contamination of stream sediments in the North Bohemian Coal District
      (Czech Republic): Mercury speciation and the role of organic matter.
AB  - Industrial expansion in the North Bohemian Coal District over the past decades
      has had an adverse effect not only on stream sediments but also on the freshwater
      system. So far mercury occurrence has not been properly investigated in the area.
      In response to this situation, the present study applies mercury quantification
      and speciation in order to predict the possible mobility of mercury. The
      enrichment factor (EF) and sediment quality guidelines (SQGs) were used to
      calculate the degree of mercury contamination. An automatic mercury analyser was
      employed to detect the total mercury content (Hg-T) and Thermal Desorption
      technique was used to identify mercury species. All the sediment samples were
      assessed with the contamination degree which increased to very severe in stream
      sediments in the middle section of the river course. Mercury species identified
      were chiefly the insoluble forms Hg-FeS2 and HgS. Lignite components and
      combustion residues were identified as the primary source of Hg contamination in
      the area.

PMID- 30098563
TI  - Delineating the origin of Pb and Cd in the urban dust through elemental and
      stable isotopic ratio: A study from Hangzhou City, China.
AB  - Urban dust (UD) is one of the main sinks of heavy metals in urban environments;
      however, the sources of these heavy metals are quite difficult to identify. A
      total of 78 UD samples were collected bi-monthly from October 2012 to August
      2013, including 13 sites from three functional areas (residential areas, city
      parks, and main roads) and the Botanic Garden as a control district. The metal
      ratios and lead isotopic ratios combined with correlation analysis were used to
      identify the sources of Pb and Cd in the UD samples. In the scatter plot of Cd/Mn
      vs Pb/Mn, the dust samples could be classified into four groups showing their
      different sources and characteristics. Lead isotopic composition analysis
      indicated that coal combustion was the main source of Pb for residential dusts,
      while automobile exhaust emission for road dusts. Correlation analysis revealed
      that the abraded paints was a main contribution of Cd in UD, especially those in
      city parks. The research provides a useful method of combining multiple
      approaches to identify sources of metal elements in UD.

PMID- 30098564
TI  - Biological treatment of selenium-laden wastewater containing nitrate and sulfate
      in an upflow anaerobic sludge bed reactor at pH 5.0.
AB  - This study investigated the removal of selenate (SeO42-), sulfate (SO42-) and
      nitrate (NO3-) at different influent pH values ranging from 7.0 to 5.0 and 20 
      degrees C in an upflow anaerobic sludge blanket (UASB) reactor using lactate as
      an electron donor. At pH 5.0, the UASB reactor showed a 20-30% decrease in
      reactor performance compared to operation at pH 5.5 to 7.0, reaching removal
      efficiencies of 79%, 15%, 43% and 61% for NO3-, SO42-, Setotal and Sediss,
      respectively. However, the reactor stability was an issue upon lowering the pH to
      5.0 and further experiments are recommended. The sludge formed during low pH
      operation had a fluffy, floc-like appearance with filamentous structure, possibly
      due to the low polysaccharide (PS) to protein (PN) ratio (0.01 PS/PN) in the
      soluble extracellular polymeric substances (EPS) matrix of the biomass. Scanning
      electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) analysis
      of the sludge confirmed Se oxyanion reduction and deposition of Se0 particles
      inside the biomass. Microbial community analysis using Illumina MiSeq sequencing
      revealed that the families of Campylobacteraceae and Desulfomicrobiaceae were the
      dominant phylotypes throughout the reactor operation at approximately 23% and 10%
      relative abundance, respectively. Furthermore, approximately 10% relative
      abundance of both Geobacteraceae and Spirochaetaceae was observed in the granular
      sludge during the pH 5.0 operation. Overall, this study demonstrated the
      feasibility of UASB operation at pH values ranging from 7.0 to 5.0 for removing
      Se and other oxyanions from wastewaters.

PMID- 30098565
TI  - Headspace passive dosing of volatile hydrophobic chemicals - Aquatic toxicity
      testing exactly at the saturation level.
AB  - It is challenging to conduct aquatic tests with highly hydrophobic and volatile
      chemicals while avoiding substantial sorptive and evaporative losses. A simple
      and versatile headspace passive dosing (HS-PD) method was thus developed for such
      chemicals: The pure liquid test chemical was added to a glass insert, which was
      then placed with the open end in the headspace of a closed test system containing
      aqueous test medium. The test chemical served as the dominating partitioning
      donor for establishing and maintaining maximum exposure levels in the headspace
      and aqueous solution, without direct contact between the donor and the test
      medium. The HS-PD method was cross validated against passive dosing with a
      saturated silicone elastomer, using headspace gas chromatography as analytical
      instrument and saturated vapors as reference. The HS-PD method was then applied
      to control the exposure in algal growth inhibition tests with the green algae
      Raphidocelis subcapitata. The model chemicals were C9-C14 n-alkanes and the
      cyclic volatile methyl siloxanes octamethyltetracyclosiloxane (D4) and
      decamethylpentacyclosiloxane (D5). Growth rate inhibition at the solubility limit
      was 100% for C9-C13 n-alkanes and 53 +/- 31% (95% CI) for tetradecane. A moderate
      inhibition of 11 +/- 4% (95% CI) was observed for D4, whereas no inhibition was
      observed for D5. The present study introduces an effective method for aquatic
      toxicity testing of a difficult-to-test group of chemicals and provides an
      improved experimental basis for investigating toxicity cut-offs.

PMID- 30098566
TI  - Combined intra- and extracellular reduction involved in the anaerobic
      biodecolorization of cationic azo dye by Shewanella oneidensis MR-1.
AB  - Microbial reduction decolorization is a promising strategy for cationic azo dye
      pollution remediation, but the reduction mechanism is unclear yet. In this work,
      the anaerobic reduction decolorization mechanism of cationic red X-GRL (X-GRL) by
      Shewanella oneidensis MR-1 (MR-1) was investigated from both intracellular and
      extracellular aspects. The exogenous additional riboflavin treatment test was
      used to analyze the extracellular reduction mechanism of X-GRL, and the actual
      role of riboflavin during the reduction of X-GRL was identified by three
      dimensional fluorescence analysis for the first time. The proteinase K and the
      electron competitor treatment tests were used to analyze the intracellular
      reduction mechanism of X-GRL. Moreover, the effect of external environment on the
      reduction mechanism of X-GRL was elucidated by the decolorization performance of
      MR-1 wild type and its mutants, DeltaomcA/mtrC, DeltamtrA, DeltamtrB and
      DeltacymA, under different external pH conditions. The results indicated that X
      GRL could be decolorized by MR-1 in both extracellular and intracellular spaces.
      The extracellular decolorization of X-GRL could be caused by Mtr respiratory
      pathway or the indirect reduction of riboflavin, while the intracellular
      decolorization might occur due to the intracellular reduction depending on CymA
      pathway and a NADH-dependent reduction catalyzed by intracellular azoreductases.
      Furthermore, the proportion of extracellular decolorization decreased, whereas
      that of intracellular decolorization increased as the environmental pH rose.

PMID- 30098567
TI  - Do Anti-Epileptic Drug modifications after first trimester of pregnancy influence
      fetal malformation or cognitive outcome?
AB  - OBJECTIVE: The management of Women With Epilepsy (WWE) in pregnancy is a
      challenge that demands balancing the risks of Major Congenital Malformation (MCM)
      on one hand with adequate seizure control on the other. While most studies have
      analysed the risks of Anti-Epileptic Drugs (AED) exposure in the first trimester,
      AED changes during the second and third trimester and their effects on fetal
      outcome has not been studied adequately. MATERIALS AND METHODS: Data of WWE who
      were prospectively followed up and completed pregnancy with live birth under the
      Kerala registry of epilepsy and pregnancy (KREP) between 1998 and 2014 were
      analysed. The AED addition, dose escalation, unchanged continuation, dose
      reduction or stoppage during the second or third trimester in comparison to the
      first trimester was tabulated for each drug. The outcome measures evaluated were
      malformation status and Developmental Quotient (DQ) at one year as extracted from
      the clinical records of the registry. RESULTS: The first trimester AED exposure
      was nil for 231, monotherapy for 925 and polytherapy for 391 WWE. WWE on
      monotherapy in first trimester were more likely to remain on the same number of
      AEDs in second or third trimester than those who were on polytherapy (OR 3.1, 95%
      CI 2.2 - 4.46). AED naive women had a higher likelihood (OR 16.7; 95% CI 10.9
      25.8) of being started on AED than women on monotherapy being switched to
      polytherapy. At least one AED was reduced or stopped during second or third
      trimester more often in women on polytherapy (15.1%) than in women on monotherapy
      (3.7%) (OR 4.7; 95% CI 2.9-7.2). Malformation rates for the infants of women
      whose AED dosage was increased or added were not significantly different from
      those of others. There was no statistically significant change in DQ with
      increase in dose or addition of drugs in the second or third trimester.
      CONCLUSION: AEDs were reduced in a significant proportion of patients on
      polytherapy while more than a third of women who were not on AEDs in the first
      trimester were subsequently started on AEDs. Increase in dose or addition of AEDs
      after the first trimester is unlikely to influence malformation outcome but the
      potential adverse effect on the DQ needs to be explored on a larger set of data.

PMID- 30098568
TI  - Effect of nano-structural properties of biomimetic hydroxyapatite on
      osteoimmunomodulation.
AB  - Immune cells are sensitive to the microstructural and textural properties of
      materials. Tuning the structural features of synthetic bone grafts could be a
      valuable strategy to regulate the specific response of the immune system, which
      in turn modulates the activity of bone cells. The aim of this study was to
      analyse the effect of the structural characteristics of biomimetic calcium
      deficient hydroxyapatite (CDHA) on the innate immune response of macrophages and
      the subsequent impact on osteogenesis and osteoclastogenesis. Murine RAW 264.7
      cells were cultured, under standard and inflammatory conditions, on chemically
      identical CDHA substrates that varied in microstructure and porosity. The impact
      on osteogenesis was evaluated by incubating osteoblastic cells (SaOS-2) with RAW
      CDHA conditioned extracts. The results showed that macrophages were sensitive to
      different textural and structural properties of CDHA. Under standard conditions,
      the impact of inflammatory cytokine production by RAW cells cultured on CDHA
      played a significant role in the degradation of substrates, suggesting the impact
      of resorptive behaviour of RAW cells on biomimetic surfaces. Osteoblast
      differentiation was stimulated by the conditioned media collected from RAW cells
      cultured on needle-like nanostructured CDHA. The results demonstrated that needle
      like nanostructured CDHA was able to generate a favourable osteoimmune
      environment to regulate osteoblast differentiation and osteogenesis. Under
      inflammatory conditions, the incubation of RAW cells with less porous CDHA
      resulted in a decreased gene expression and release of pro-inflammatory
      cytokines.

PMID- 30098569
TI  - Large-scale production of stem cells utilizing microcarriers: A biomaterials
      engineering perspective from academic research to commercialized products.
AB  - Human stem cells, including pluripotent, embryonic and mesenchymal, stem cells
      play pivotal roles in cell-based therapies. Over the past decades, various
      methods for expansion and differentiation of stem cells have been developed to
      satisfy the burgeoning clinical demands. One of the most widely endorsed
      technologies for producing large cell quantities is using microcarriers (MCs) in
      bioreactor culture systems. In this review, we focus on microcarriers properties
      that can manipulate the expansion and fate of stem cells. Here, we provide an
      overview of commercially available MCs and focus on novel stimulus responsive MCs
      controlled by temperature, pH and field changes. Different features of MCs
      including composition, surface coating, morphology, geometry/size, surface
      functionalization, charge and mechanical properties, and their cellular effects
      are also highlighted. We then conclude with current challenges and outlook on
      this promising technology.

PMID- 30098571
TI  - Hypoxia-responsive block copolymer radiosensitizers as anticancer drug
      nanocarriers for enhanced chemoradiotherapy of bulky solid tumors.
AB  - Radiosensitizers play an important role in the clinical radiotherapy of hypoxic
      solid tumors to improve therapeutic efficacy. However, the in vivo performance of
      clinically used small-molecule radiosensitizers is commonly compromised by low
      bioavailability in hypoxic tumor regions. Herein, amphiphilic block copolymer
      radiosensitizers are prepared from clinically approved poly(ethylene glycol)
      block-poly(l-glutamic acid) (PEG-b-PLG) and metronidazole (MN) to obtain MN
      grafted PEG-b-PLG (PEG-b-P(LG-g-MN)) via condensation reaction, which can self
      assemble into core-shell micelles as nanoparticle-formulated radiosensitizers in
      aqueous solution. The radiosensitizers are demonstrated to possess significantly
      higher sensitization enhancement ratio (SER) of 2.18 and potent in vivo tumor
      ablation capability upon exposure to electron beam irradiation compared with
      clinically used sodium glycididazole (GS) with SER of 1.32. Moreover, after
      optimizing the ratios of carboxyl and MN groups, PEG-b-P(LG-g-MN) micelles can be
      used to encapsulate doxorubicin (DOX@HMs) efficiently. Hypoxia-responsive
      structural transformation of MN into hydrophilic aminoimidazole triggers fast DOX
      release from DOX@HMs. After intravenous injection of DOX@HMs, potent ablation
      capability against bulky solid tumors (~500 mm3) is realized at a low radiation
      dose (4 Gy) via enhanced chemoradiotherapy. Therefore, the developed novel
      amphiphilic block copolymer radiosensitizers can be concurrently used as high
      efficiency radiosensitizers and hypoxia-responsive DOX nanocarriers for enhanced
      chemoradiotherapy.

PMID- 30098570
TI  - Optimal electrical stimulation boosts stem cell therapy in nerve regeneration.
AB  - Peripheral nerve injuries often lead to incomplete recovery and contribute to
      significant disability to approximately 360,000 people in the USA each year. Stem
      cell therapy holds significant promise for peripheral nerve regeneration, but
      maintenance of stem cell viability and differentiation potential in vivo are
      still major obstacles for translation. Using a made-in-house 96-well vertical
      electrical stimulation (ES) platform, we investigated the effects of different
      stimulating pulse frequency, duration and field direction on human neural crest
      stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced
      neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100MUs
      pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a
      novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo
      transplantation following peripheral nerve regeneration. 15 mm critical-sized
      sciatic nerve injuries were generated with subsequent surgical repair in sixty
      athymic nude rats. Injured animals were randomly assigned into five groups (N =
      12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft.
      The optimized ES was applied immediately after surgical repair for 1 h in ES and
      NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis),
      wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6
      or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass
      measurements in ES + NCSC group were comparable to autologous nerve
      transplantation and significantly higher than other groups (p < 0.05).
      Quantitative histomorphometric analysis and catwalk gait analysis showed similar
      improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown
      via immunochemical analysis, with higher Schwann cell (SC) differentiation in the
      NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC
      transplantation significantly enhanced nerve regeneration after injury and
      repair, and was comparable to autograft treatment. Thus, ES can be a potent
      alternative to biochemical and physical cues for modulating stem cell survival
      and differentiation. This novel cell-based intervention presents an effective and
      safe approach for improved outcomes after peripheral nerve repair.

PMID- 30098572
TI  - The effect of enteral versus parenteral nutrition for critically ill patients: A
      systematic review and meta-analysis.
AB  - STUDY OBJECTIVE: To analyze the effect of enteral nutrition compared with
      parenteral nutrition in critically ill patients. DESIGN: Systematic review and
      meta-analysis of randomized controlled trials. SETTING: Intensive care unit.
      PATIENTS: 23 trials containing 6478 patients met our inclusion criteria.
      INTERVENTION: A systematical literature search was conducted to identify eligible
      trials in electronic databases including PubMed, Embase, Scopus, EBSCO and
      Cochrane Library. The primary outcome was mortality, the secondary outcomes were
      gastrointestinal complications, bloodstream infections, organ failures, length of
      stay in ICU and hospital. We performed a predefined subgroup analyses to explore
      the treatment effect by mean age, publication date and disease types. MAIN
      RESULTS: The result showed no significant effect on overall mortality rate (OR
      0.98, 95%CI 0.81 to 1.18, P = 0.83, I2 = 19%) and organ failure rate (OR 0.87,
      95%CI 0.75 to 1.01, P = 0.06, I2 = 16%). The use of EN had more beneficial
      effects with fewer bloodstream infections when compared to PN (OR 0.59, 95%CI
      0.43 to 0.82, P = 0.001, I2 = 27%) and this was more noteworthy in the subgroup
      analysis for critical surgical patients (OR 0.36, 95%CI 0.22 to 0.59, P < 0.0001,
      I2 = 0%). EN was associated with reduction in hospital LOS (MD -0.90, 95%CI -1.63
      to -0.17, P = 0.21, I2 = 0%) but had an increase incidence of gastrointestinal
      complications (OR 2.00, 95%CI 1.76 to 2.27, P < 0.00001, I2 = 0%). CONCLUSION:
      For critically ill patients, the two routes of nutrition support had no different
      effect on mortality rate. The use of EN could decrease the incidence of
      bloodstream infections and reduce hospital LOS but was associated with increased
      risk of gastrointestinal complications.

PMID- 30098574
TI  - Limitations of the Erector Spinae Plane (ESP) block for radical mastectomy.

PMID- 30098573
TI  - Partial hepatic resections for metastatic neuroendocrine tumors: perioperative
      outcomes.
AB  - STUDY OBJECTIVE: Partial hepatic resection reduces tumor burden in patients with
      metastatic neuroendocrine tumors, thereby improving quality and length of life.
      These procedures can be challenging as well as life-threatening. Our aim was to
      evaluate our patients' perioperative outcomes and propose a definition for an
      intraoperative carcinoid crisis relevant to this surgery, given its unique
      surgical considerations. DESIGN: Retrospective study. SETTING: Mayo Clinic,
      Rochester, Minnesota. PATIENTS: One hundred sixty-nine patients undergoing
      partial hepatic resection for metastatic neuroendocrine tumors between 1997 and
      2015 were identified retrospectively from a surgical database at Mayo Clinic
      Rochester. INTERVENTIONS: None. MEASUREMENTS: Intraoperative carcinoid crisis for
      patients undergoing hepatic resection of neuroendocrine tumors was defined.
      Patients' medical records were reviewed and data were abstracted describing
      patient and procedural characteristics and perioperative outcomes. MAIN RESULTS:
      There were no documented cases of carcinoid crisis (0.0%, 95% C.I. 0.0% to 2.2%).
      One patient developed clinical findings of an emerging carcinoid crisis, but was
      successfully treated with doses of octreotide and findings resolved in <10 min.
      Prophylactically 500 MUg octreotide was given subcutaneously in 77% (130/169) of
      patients preoperatively. CONCLUSIONS: There were no documented cases of carcinoid
      crisis (0.0%, 95% C.I. 0.0% to 2.2%). Adverse events were infrequent.

PMID- 30098575
TI  - Non-invasive positive pressure ventilation in lung transplant recipients with
      acute respiratory failure: Beyond the perioperative period.
AB  - PURPOSE: The purpose of this study is to evaluate outcomes in MICU lung
      transplant recipients with acute respiratory failure treated with non-invasive
      positive pressure ventilation (NPPV) and identify factors associated with NPPV
      failure (need for intubation). METHODS: Retrospective chart review of all lung
      transplant recipients who were admitted with acute respiratory failure to the
      MICU from January 2009-August 2016 was completed. Logistic regression analysis
      was performed to determine which factors were independently associated with NPPV
      failure. RESULTS: Of 156 patients included in the study, 125 (80.1%) were tried
      on NPPV. Sixty-eight (54.4%) were managed successfully with NPPV with a hospital
      survival rate of 94.1%. Subjects who failed NPPV had higher hospital mortality,
      similar to those intubated from the outset (15 [48.3%]; 22 [38.6%], p = .37). In
      multivariate analyses, APACHE III scores >78 (9.717 [3.346, 28.22]) and PaO2/FiO2
      <= 151 (4.54 [1.72, 11.99]) were associated with greater likelihood of NPPV
      failure. There was no difference in NPPV failure based on the presence of BOS. In
      patients with high severity of illness, there was no difference in mortality
      between initial IMV and NPPV failure when stratified on the basis of hypoxemia
      (PaO2/FiO2 > 151, p-value 0.34; PaO2/FiO2 <= 151, p-value 0.99). CONCLUSIONS:
      NPPV is a viable option for lung transplant recipients with acute respiratory
      failure. Extreme caution should be exercised when used in patients with high
      severity of illness (APACHE III >78) and/or severe hypoxemia (PaO2/FiO2 <= 151).

PMID- 30098576
TI  - The use of video vignettes to measure health worker knowledge. Evidence from
      Burkina Faso.
AB  - The quality of care is a crucial determinant of good health outcomes, but is
      difficult to measure. Survey vignettes are a standard approach to measuring
      medical knowledge among health care providers. Given that written vignettes or
      knowledge tests may be too removed from clinical practice, particularly where
      "learning by doing" may be an important form of training, we developed a new type
      of provider vignette. It uses videos presenting a patient visiting the clinic
      with maternal/early childhood symptoms. We tested these video vignettes with
      current and future (students) health professionals in Burkina Faso. Participants
      indicated that the cases used were interesting, understandable and common. Their
      performance was consistent with expectations. Participants with greater training
      (medical doctors vs. nurses and midwives) and experience (health professionals
      vs. students) performed better. The video vignettes can easily be embedded in
      computers, tablets and smart phones; they are a convenient tool to measure
      provider knowledge; and they are cost-effective instruction and testing tools.

PMID- 30098578
TI  - In vitro lesion bypass by human PrimPol.
AB  - Many human DNA polymerases bypass DNA damage during translesion synthesis (TLS).
      Human primase and polymerase, PrimPol, assists fork progression by repriming DNA
      synthesis downstream of the lesion using its DNA primase activity. We tested the
      properties of PrimPol as a TLS polymerase in the presence of different metal ions
      in vitro. We demonstrate that in the presence of Mg2+ ions PrimPol carries out
      efficient and relatively accurate synthesis past 8-oxoguanine and 5-formyluracil.
      It also bypasses an abasic site and O6-methylguanine, but is blocked by thymine
      glycol and 1,N6-ethenoadenine. Substitution of Mg2+ with Mn2+ stimulates the TLS
      activity of PrimPol and allows for efficient, but error-prone, synthesis on DNA
      templates containing all tested DNA lesions, including thymine glycol and 1,N6
      ethenoadenine. The TLS activity of PrimPol has possible relevant functions in
      vivo; e.g., the combined primase and DNA polymerase activities of PrimPol might
      facilitate replication of DNA with clustered damage.

PMID- 30098577
TI  - DNArCdb: A database of cancer biomarkers in DNA repair genes that includes
      variants related to multiple cancer phenotypes.
AB  - Functioning DNA repair capabilities are vital for organisms to ensure that the
      biological information is preserved and correctly propagated. Disruptions in DNA
      repair pathways can result in the accumulation of DNA mutations, which may lead
      to onset of complex disease such as cancer. The discovery and characterization of
      cancer-related biomarkers may allow early diagnosis and targeted treatment, which
      could significantly contribute to the survival rates of cancer patients. To this
      end, we have applied a hypothesis driven bioinformatics approach to identify
      biomarkers related to 25 different DNA repair enzymes, in combination with
      structural analysis of six selected missense mutations of newly discovered SNPs
      that are associated with cancer phenotypes. Our search on 8 distinct cancer
      databases uncovered 43 missense SNPs that statistically significantly associated
      at least one phenotype. Moreover, nine of these missense SNPs are statistically
      significantly associated with two or more cancers. In addition, we have performed
      classical molecular dynamics to characterize the impact of rs10018786 on POLN,
      which results in the M310 L Pol nu variant, and rs3218784 on POLI, which results
      in the I236 M Pol iota. Our results suggest that both of these cancer-associated
      variants result in noticeable structural and dynamical changes compared with
      their respective wild-type proteins.

PMID- 30098579
TI  - MicroRNA-375 inhibits the proliferation, migration and invasion of kidney cancer
      cells by triggering apoptosis and modulation of PDK1 expression.
AB  - Kidney cancer is one of the deadly cancers and is the cause of significant number
      of deaths worldwide. The treatments used for the treatment of kidney cancer are
      limited and associated with number of side effects. Therefore, there is need for
      the development of new drug options or to identify novel therapeutic targets for
      the treatment of kidney cancer. In this study we investigated the potential of
      miR-375 as the therapeutic target for the treatment of Kidney cancer. The results
      revealed that miR-375 is significantly downregulated in the Kidney cancer cells.
      To investigate the role therapeutic potential of miR-375, one kidney cancer cell
      line (A-498) was selected for further experimentation. It was observed that
      overexpression of miR-375 inhibits A-498 kidney cancer proliferation by induction
      of apoptosis. In addition, overexpression of miR-375 causes suppression of
      migration and invasion of the A-498 kidney cancers cells. Bioinformatic analysis
      revealed PDK1 to be putative target of miR-375 in Kidney cancer cells. The
      western blot analysis revealed the expression of PDK1 to be significantly
      upregulated in Kidney cancer cells and overexpression of miR-375 in A-498 cells
      caused inhibition of PDK1 preventing the phosphorylation of AKT (Thr308 and
      Ser473). Additionally, inhibition of PDK1 had similar effects as that of miR-375
      overexpression on cell proliferation of A-498 kidney cancer cells. The inhibition
      of miR-375 expression could not rescue the effects of PDK-1 suppression on A-498
      cell proliferation. In contrary, overexpression of PKD1 in A-498 cells
      transfected with miR-375 mimics could nullify the effects of miR-375 on
      proliferation of the A-498 cells. Taken together, we conclude that miR-375
      regulates cell proliferation, migration and invasion of A-498 kidney cancer cells
      and may prove to be an important therapeutic target.

PMID- 30098580
TI  - 4-tert-octylphenol injures motility and viability of human sperm by affecting
      cAMP-PKA/PKC-tyrosine phosphorylation signals.
AB  - 4-tert-octylphenol (4t-OP) is a well-known xenoestrogen. Our objective was to
      explore the effects and molecular mechanisms of 4t-OP on human sperm. Sperm
      samples were exposed to 0, 0.1, or 0.3 mM 4t-OP for two hours. Results showed
      that both sperm viability and motility were significantly injured by 0.3 mM 4t
      OP. We applied comparative proteomics to explore the molecular targets affected
      by 4t-OP. 81 differentially expressed (DE) proteins were identified.
      Bioinformatic analysis showed that these proteins were highly associated with
      motility and apoptosis, and were mostly enriched in cAMP-PKA/PKC-phosphorylation
      associated pathway. We further verified that 0.1 mM and 0.3 mM 4t-OP
      significantly decreased cAMP activity of sperm. Expression of RACK1 and PRDX6
      were detected by western blot (WB) to verify their tendencies in gels;
      antiapoptotic factor BCL2 was also detected by WB. The data indicated that 4-tert
      octylphenol injures the motility and viability of human sperm probably by
      affecting cAMP-PKA/PKC-tyrosine phosphorylation signals.

PMID- 30098581
TI  - Discriminating power of rapidly mutating Y-STRs in deep rooted endogamous
      pedigrees from Sindhi population of Pakistan.
AB  - Rapidly mutating Y-STRs (RM Y-STRs) have been paid much attention in recent
      years. The 13 RM Y-STRs (DYF387S1, DYF399S1, DYF403S1a/b, DYF404S1, DYS449,
      DYS518, DYS526I/II, DYS547, DYS570, DYS576, DYS612, DYS626, and DYS627) have been
      proved to have substantially higher haplotype diversity and discrimination
      capacity than conventionally used Y-STRs indicating the considerable power in
      paternal lineage differentiation in endogamous populations, separation of which
      is usually impossible with standard Y-STRs. In current study, we analyzed the RM
      Y-STRs and PowerPlex(r) Y23 System in 216 male relatives from 18 deep rooted
      endogamous Sindhi families from Pakistan. Mutations were frequently observed at
      DYF399S1, DYS449, DYS518DYS547 and DYF403S1b2 loci, which are known to mutate
      more rapidly than other RM Y-STRs. Overall differentiation rate with RM Y-STRs
      was as high as 32.88%, while those with PowerPlex(r) Y23 System and AmpFlSTR(r)
      YfilerTM kit were 6.85% and 3.65% respectively. The differentiation rate of RM Y
      STRs was 29.22% and 26.03% higher than those of AmpFlSTR(r) YfilerTM kit and
      PowerPlex(r) Y23 System, respectively.

PMID- 30098582
TI  - Estimation of stature and sex from sacrum and coccyx measurements by
      multidetector computed tomography in Chinese.
AB  - The present study is an attempt to estimation of stature and sex from sacrum and
      coccyx measurements by multidetector computed tomography (MDCT) in a contemporary
      Chinese population. Nine measurements for every sacrum and coccyx were taken from
      CT image of 350 Chinese. The sample is composed of 190 males and 160 females with
      an average age of 55 and 50 years, respectively. Discriminant function was used
      in sex estimation and regression analysis was used in stature estimation from
      these two bones. The stepwise analysis of all measurements yielded a sex
      classification accuracy rate of 84.9%. The classification accuracy rates of the
      univariate discriminant function analyses are 58.3%-76.9%. For stature
      estimation, the accuracy of stature prediction ranged from 4.891 to 6.107 cm for
      male, from 4.474 to 5.606 cm for female, respectively. This paper provides
      indications that the sacrum and coccyx are important bones for sex estimation and
      they could be effectively used as alternatives in forensic cases when the skull
      and pelvis are unavailable. Furthermore, the regression equations presented in
      this study may be useful for forensic estimation of the stature of Chinese
      individuals, particularly in cases where better predictors such as the long bones
      are not available.

PMID- 30098583
TI  - The processing of animacy in noun-classifier combinations in reading Korean: An
      ERP study.
AB  - A key issue in the area of language processing is the mechanism underlying the
      processing of animacy information during sentence comprehension. In this ERP
      study, we investigated the temporal dynamics of animacy processing in Korean noun
      classifier combinations that do not involve verb-noun thematic processing. We
      manipulated semantic and animacy relationships between nouns and their following
      classifiers, and there were three conditions in our experiment: (a) correct, (b)
      semantic mismatch, or (c) animacy mismatch. The results showed that both noun
      classifier mismatch conditions evoked a biphasic N400-P600 effect, but there was
      no P600 difference between the two mismatch conditions. However, further analyses
      indicated that the animacy mismatch condition evoked a less negative-going
      waveform than the semantic mismatch condition in the 400-500 ms time window. Our
      findings suggest that the brain processes animacy information differently from
      other semantic features in noun-classifier combinations in Korean, and additional
      animacy mismatch blocked further fine-grained semantic processing. The ERP
      evidence also suggests that the role of animacy in sentence comprehension varies
      according to language type and sentence structure. Whether animacy participates
      in the construction of verb-noun thematic relationships in sentences may be an
      important factor that influences the neural patterns of animacy processing in
      language comprehension.

PMID- 30098584
TI  - Solvent-free lignin recovered by thermal-enzymatic treatment using fixed-bed
      reactor technology - Economic assessment.
AB  - The economic viability of producing lignin by thermal-enzymatic treatment in a
      high-pressure fixed-bed reactor is investigated for the first time. In this
      direction, different advantages (e.g. recovery of low-odor sulfur-free lignin,
      high process flexibility) and disadvantages (e.g. high investment for high
      pressure equipment) of this technology are considered. Regarding process
      flexibility, four different operating modes (i.e. flow through, circulation) are
      investigated by varying process parameters and applications of the C5 sugar
      fraction. Therefore, a combined modelling approach is applied by using overall
      biorefinery models and a predictive fixed-bed model. At optimum process
      conditions, lignin can be produced at a competitive price (395 ?/tLignin) when
      comparing to other technical lignins. This result is achieved by using the fixed
      bed reactor only for thermal treatment, with the water consumption being the most
      important factor affecting the cost of lignin production. Compared to that the C5
      sugar recovery of the pretreatment is negligible.

PMID- 30098585
TI  - Proteomics unravel the regulating role of salicylic acid in soybean under yield
      limiting drought stress.
AB  - Drought is a major concern for sustainable yield under changing environment.
      Soybean, an economically important oil and protein crop, is prone to drought
      resulting in yield instability. Salicylic acid (SA), a multifaceted growth
      hormone, modulates a series of parallel processes to confer drought tolerance
      thereby relieving yield limitations. The present study was performed in soybean
      plants treated with SA (0.5 mM) through seed pretreatment under drought regimes:
      severe stress (50% RWC) and moderate stress (75% RWC), and rehydration.
      Differential leaf proteome profiling with morphological, physiological and
      antioxidative metabolism studies were performed at two developmental stages
      (vegetative and flowering). This explained the tolerance attribution to soybean
      throughout the development attaining yield stability. Abundance of proteins
      involved in photosynthesis and ATP synthesis generated energy driving metabolic
      processes towards plant growth, development and stress acclimation. Carbon (C)
      metabolism proteins involved in growth, osmoregulation and C partition relieved
      drought-induced C impairment under SA. Defensive mechanisms against redox
      imbalance and protein misfolding and degradation under stress were enhanced as
      depicted by the abundance of proteins involved in redox balance and protein
      synthesis, assembly and degradation at vegetative stage. Redox signaling in
      chloroplast and its interplay with SA signaling triggered different defense
      responses as shown through thioredoxin protein abundance. Amino acid metabolism
      proteins abundance resulted in increased osmoprotectants accumulation like
      proline at initial stage which contributed later towards N (nitrogen)
      remobilization to developing sink. At later stage, abundance of these proteins
      maintained redox homeostasis and N remobilization for improved sink strength. The
      redox homeostasis was supported by the increased antioxidative metabolism in SA
      treated plants. The downregulation of proteins at flowering also contributed
      towards N remobilization. Yield potential was improved by SA under drought
      through acclimation with enhanced N and C remobilization to sink as demonstrated
      by increased yield parameters like seed number and weight per plant, thousand
      seed weight and harvest index. The potential of SA in conferring drought
      tolerance to plants to maintain sustainable yield possess future research
      interests.

PMID- 30098586
TI  - Nutritional properties of Tempranillo grapevine leaves are affected by clonal
      diversity, mycorrhizal symbiosis and air temperature regime.
AB  - Tempranillo grapevine is widely cultivated in Spain and other countries over the
      world (Portugal, USA, France, Australia, and Argentina, among others) for its
      wine, but leaves are scarcely used for human or animal nutrition. Since high
      temperatures affect quality of fruits and leaves in grapevine and the association
      of Tempranillo with arbuscular mycorrhizal fungi (AMF) enhances the antioxidant
      properties of berries and leaves, we assessed the effect of elevated air
      temperature and mycorrhization, separately or combined, on the nutritional
      properties of Tempranillo leaves at the time of fruit harvest. Experimental assay
      included three clones (CL-260, CL-1048, and CL-1089) and two temperature regimes
      (24/14  degrees C or 28/18  degrees C day/night) during fruit ripening. Within
      each clone and temperature regime there were plants not inoculated or inoculated
      with AMF. The nutritional value of leaves increased under warming climate:
      elevated temperatures induced the accumulation of minerals, especially in CL
      1089; antioxidant capacity and soluble sugars also increased in CL-1089; CL-260
      showed enhanced amounts of pigments, and chlorophylls and soluble proteins
      increased in CL-1048. Results suggested the possibility of collecting leaves
      together with fruit harvest with different applications of every clone: those
      from CL-1089 would be adequate for an energetic diet and leaves from CL-260 and
      CL-1048 would be suitable for culinary processes. Mycorrhization improved the
      nutritional value of leaves by enhancing flavonols in all clones, hydroxycinnamic
      acids in CL-1089 and carotenoids in CL-260.

PMID- 30098587
TI  - Automated radiosynthesis of [18F]FBEM, a sulfhydryl site specific labeling agent
      for peptides and proteins.
AB  - In the process of developing [18F]FBEM coupled target peptide, we have instituted
      a robust automated synthesis of [18F]FBEM, a sulfhydryl (-SH) site specific agent
      for radiolabeling of peptides and proteins. The radiosynthesis generated 1.67
      3.89 GBq (45.1-105.1 mCi, 7.5-18.8% non-decay corrected yield) of [18F]FBEM from
      22.2 GBq (600 mCi) of starting [18F]fluoride with molar activity of 31.8 +/- 5.3
      GBq/umol (0.86 +/- 0.14 mCi/nmol) (n = 3) at the end of synthesis. Radiochemical
      purity was greater than 98%, and total synthesis time was ~90 min.

PMID- 30098588
TI  - Mass spectrometric method for distinguishing isomers of dexamethasone via
      fragment mass ratio: An HRMS approach.
AB  - The major challenge in identifying dexamethasone, betamethasone, and
      paramethasone from a mixture of these corticosteroids is difficulty in achieving
      an efficient separation. In this study, we aimed to develop an efficient
      technique to identify these co-eluting isomers based on the mass spectral
      patterns of them and their corresponding phase II metabolites after electrospray
      ionization. Fragmentation pathways in tandem mass spectrometry revealed
      acceptable specificity within the groups of conjugates. The method was validated
      using individual isomers and mixtures at various compositions. The effects of
      concentration and collision energies on fragmentation patterns were also studied
      extensively. Matrix-fortified equine urine and plasma samples were also included
      so that matrix effects and interferences on fragmentation ratios could be
      elucidated. Preliminary results using biological samples demonstrated the
      suitability of this analytical strategy for direct measurement from their
      fragmentation patterns. Possible fragmentation pathways for each isomer were
      proposed.

PMID- 30098589
TI  - The effects of habitat filtering and non-habitat processes on species spatial
      distribution vary across life stages.
AB  - PREMISE OF THE STUDY: Habitat filtering and non-habitat processes are two major
      processes affecting spatial distributions of species. Because trees at different
      life stages perform differently, the life stage of tree species could play an
      important role in shaping the spatial distribution of species and community
      assembly. Here, we examined the possible changes of spatial distributions of
      species and evaluated the shifts in the relative importance of habitat filtering
      and non-habitat processes across life stages in a 50-ha subtropical forest plot
      in China. METHODS: We modeled species distribution with and without life stages
      using three point process models. The performance of these models, with and
      without considering life stages, was evaluated by comparing the species-area
      curve and the degree of clustering. The relative effects of habitat filtering and
      non-habitat processes across life stages were quantified using a spatial variance
      decomposition method. KEY RESULTS: The incorporation of life stage considerably
      improved the goodness-of-fit of these point process models at both the community
      and species levels. Non-habitat processes explained about 90% of the total
      variation in spatial distribution, while habitat filtering explained about 10%.
      The relative importance of habitat filtering only increased slightly from sapling
      to adult stages. CONCLUSIONS: Point process models performed better when life
      stages are included, indicating the importance of considering life stage when
      modeling spatial distributions for understanding community assembly. The finding
      that habitat acts weakly and non-habitat processes act dominantly in determining
      spatial distributions of species suggests a strong dependence of spatial patterns
      on non-habitat processes.

PMID- 30098590
TI  - A model for internal medicine physicians in a small rural hospital.
AB  - CONTEXT: Finding providers to work in the hospitals and clinics in the small
      towns of the USA is a significant struggle. In the traditional model, the primary
      care doctor sees patients in the inpatient setting in addition to a clinic
      practice. In the usual hospitalist model, providers specialize to work only in
      the inpatient setting. ISSUES: Rural communities often lack the resources,
      facilities, and volume to safely adopt the usual hospitalist model, which has its
      own disadvantages. Small town hospitals have found several ways to find a middle
      ground between the two models. A provider staffing model is described that
      utilizes internal medicine physicians to provide inpatient and consultative
      outpatient care in a rural 10-bed hospital in Washington State. The hospital is
      located in a town with a population of about 3100, in a county with an
      approximate population of 70 000 people. It has a 24-hour emergency room, three
      primary care clinics, urgent care, X-ray, pharmacy, and laboratory capabilities.
      In this model, the internist on duty provides care in the inpatient unit and in
      the afternoon sees patients consulted from primary care providers, as well as
      follow-up patients from the emergency room and the inpatient setting. LESSONS
      LEARNED: The model potentially increases access to a higher level of care in the
      rural setting. It potentially provides work that for the provider is interesting,
      satisfying, balanced, purposeful, and appropriate to their training level.
      Specific norms, standards, and leadership are key to functionality, including
      some continued experience in a larger hospital. The model has been functioning
      successfully for more than 3 years. The potential cost savings over the usual
      hospitalist model are substantial. The model could be used in other locations and
      in training internal medicine physicians in the rural setting. Research in this
      area could include randomizing communities to this and other staffing models and
      following the care given and the health of the community members over time.

PMID- 30098591
TI  - Ramadan fasting alters food patterns, dietary diversity and body weight among
      Ghanaian adolescents.
AB  - BACKGROUND: Ramadan is a monthlong fast for healthy adolescents and adult
      Muslims. The quality of foods eaten and eating patterns in Ramadan may be
      different from other months of the year. Food intake of adolescents is a concern
      as energy and nutrient requirements are higher and needed to support the growth
      spurt of this stage. The objective of the present study was to describe the food
      patterns, dietary diversity and body weight changes among adolescents during
      Ramadan. METHODS: A prospective cohort study design with four measurement points
      (baseline, midline, endline and post endline) was conducted among 366 adolescents
      in Junior High Schools. Food pattern was assessed with a food frequency
      questionnaire, a 24-h dietary recall was used to assess dietary diversity and
      body weight was measured using an electronic scale. A repeated measures ANOVA was
      used to compare changes in dietary diversity scores (DDS) and weight of pupils.
      RESULTS: Half of the pupils (50.3%) were female and average age was 15.9 +/- 1.8
      years. Pupils fasted for an average of 28.3 +/- 4.0 days and 14.3 +/- 0.5 h a day
      (dawn to dusk) during Ramadan. The number and types of dishes taken at meal times
      differed substantially between Ramadan periods and outside Ramadan. Consumption
      of vitamin A-rich fruits, other fruits, and milk and milk products increased
      markedly during Ramadan. However, fasting came with a reduction in consumption of
      foods from roots and tubers, legumes and nuts, and dark green leafy vegetables
      while other food groups remained unchanged. Mean DDS increased significantly
      during Ramadan (F (2.933, 1070.573) = 7.152, p < 0.001) while mean daily meal
      frequency decreased (F (2.936, 1071.623) = 51.653, p < 0.001). There was
      significant body weight loss (-1.5 kg (95% CI: -1.1 kg to -1.6 kg)) among
      adolescents (F (2.656, 958.95) = 304.90, p < 0.001). Weight loss was short-lived;
      regained one month after Ramadan. CONCLUSION: In this prospective cohort study
      among schooling Ghanaian adolescents who fast during Ramadan, fasting was
      characterised by marked changes in usual food patterns, increased dietary
      diversity and significant body weight loss.

PMID- 30098592
TI  - Comparison of cervical cancer screening among women with and without
      hysterectomies: a nationwide population-based study in Korea.
AB  - BACKGROUND: Cervical cancer screening is not recommended for women who underwent
      hysterectomy with no history of cervical intraepithelial neoplasia (CIN) of grade
      2 or higher. We aimed to determine the cervical cancer screening rate in Korean
      women who underwent hysterectomies and compare it to that in women with intact
      uteri. METHODS: We used data from the 2014-2016 Korean National Cancer Screening
      Survey; 6807 women aged 30-74 years were included in the study. Participants were
      asked about their experiences with cervical cancer screening, hysterectomy
      status, and other variables associated with cancer screening. RESULTS: The
      screening rates among women who have undergone a hysterectomy vs. those who have
      not during the past 2 years were 61.8% (95% confidence interval [CI], 58.8-64.9)
      and 64.7% (95% CI, 64.1-65.3), respectively. Among younger women (30-44 years)
      and women with a family history of cancer, those with hysterectomies showed a
      higher cervical cancer screening rate than those without (77.8% vs. 57.1% and
      75.0% vs. 67.1%, respectively). CONCLUSIONS: Despite available evidence and
      clinical recommendations, a considerable number of Korean women who no longer
      have a cervix continue to undergo unnecessary cervical cancer screening. It is
      necessary to identify the exact underlying causes for this phenomenon, and
      systematic efforts are required to prevent unnecessary screening for women who
      have undergone a hysterectomy.

PMID- 30098593
TI  - Continuous hemofiltration improves the prognosis of bacterial sepsis complicated
      by liver dysfunction in children.
AB  - BACKGROUND: Liver dysfunction is an independent risk factor for poor prognosis of
      patients with sepsis. The aim of this study is to evaluate the effects of
      continuous hemofiltration in patients with bacterial sepsis complicated by liver
      dysfunction. METHODS: We retrospectively analyzed the medical records of 27 cases
      of bacterial sepsis with liver dysfunction admitted to pediatric intensive care
      unit (PICU) of Shanghai Children's Hospital between January 2013 and December
      2016. RESULTS: 28-day mortality and length of PICU stay were significantly
      reduced in the continuous hemofiltration group (n = 16) compared with the
      conventional management group (n = 11) (31.3% vs. 72.7%, 9 [4-23] vs. 14 [4-36],
      respectively, both P < 0.05). The interval time between PICU admission and
      continuous hemofiltration initiation was (22.06 +/- 17.68) h, and the median time
      of continuous hemofiltration duration was 48 h (31-70 h). After 72 h
      hemofiltration, the levels of total bilirubin (TBIL), direct bilirubin (DBIL),
      total bile acids (TBA), ammonia, lactate (Lac), TNF-alpha and IL-6 were
      significantly decreased in the continuous hemofiltration group. Moreover,
      multivariate logistic regression analysis indicated that continuous
      hemofiltration treatment and the TBIL level were independently associated with 28
      day mortality of patients with bacterial sepsis complicated by liver dysfunction.
      CONCLUSIONS: Continuous hemofiltration significantly decreases the serum levels
      of TBIL, DBIL, TBA, Lac, ammonia, TNF-alpha, IL-6, and improves 28-day mortality
      of patients with bacterial sepsis complicated by liver dysfunction.

PMID- 30098594
TI  - Anti-CD52 antibody treatment depletes B cell aggregates in the central nervous
      system in a mouse model of multiple sclerosis.
AB  - BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune disease of the
      central nervous system (CNS) for which several new treatment options were
      recently introduced. Among them is the monoclonal anti-CD52 antibody alemtuzumab
      that depletes mainly B cells and T cells in the immune periphery. Considering the
      ongoing controversy about the involvement of B cells and in particular the
      formation of B cell aggregates in the brains of progressive MS patients, an in
      depth understanding of the effects of anti-CD52 antibody treatment on the B cell
      compartment in the CNS itself is desirable. METHODS: We used myelin basic protein
      (MBP)-proteolipid protein (PLP)-induced experimental autoimmune encephalomyelitis
      (EAE) in C57BL/6 (B6) mice as B cell-dependent model of MS. Mice were treated
      intraperitoneally either at the peak of EAE or at 60 days after onset with 200
      MUg murine anti-CD52 vs. IgG2a isotype control antibody for five consecutive
      days. Disease was subsequently monitored for 10 days. The antigen-specific B
      cell/antibody response was measured by ELISPOT and ELISA. Effects on CNS
      infiltration and B cell aggregation were determined by immunohistochemistry.
      Neurodegeneration was evaluated by Luxol Fast Blue, SMI-32, and Olig2/APC
      staining as well as by electron microscopy and phosphorylated heavy neurofilament
      serum ELISA. RESULTS: Treatment with anti-CD52 antibody attenuated EAE only when
      administered at the peak of disease. While there was no effect on the production
      of MP4-specific IgG, the treatment almost completely depleted CNS infiltrates and
      B cell aggregates even when given as late as 60 days after onset. On the
      ultrastructural level, we observed significantly less axonal damage in the spinal
      cord and cerebellum in chronic EAE after anti-CD52 treatment. CONCLUSION: Anti
      CD52 treatment abrogated B cell infiltration and disrupted existing B cell
      aggregates in the CNS.

PMID- 30098595
TI  - LncRNA DLEU1 contributes to colorectal cancer progression via activation of
      KPNA3.
AB  - BACKGROUND: Accumulating evidences show that long noncoding RNAs (lncRNA) play
      essential roles in the development and progression of various malignancies.
      However, their functions remains poorly understood and many lncRNAs have not been
      defined in colorectal cancer (CRC). In this study, we investigated the role of
      DLEU1 in CRC. METHODS: Quantitative real-time PCR was used to detect the
      expression of DLEU1 and survival analysis was adopted to explore the association
      between DLEU1 expression and the prognosis of CRC patients. CRC cells were stably
      transfected with lentivirus approach and cell proliferation, migration, invasion
      and cell apoptosis, as well as tumorigenesis in nude mice were performed to
      assess the effects of DLEU1 in BCa. Biotin-coupled probe pull down assay, RNA
      immunoprecipitation and Fluorescence in situ hybridization assays were conducted
      to confirm the relationship between DLEU1 and SMARCA1. RESULTS: Here we revealed
      that DLEU1 was crucial for activation of KPNA3 by recruiting SMARCA1, an
      essential subunit of the NURF chromatin remodeling complex, in CRC. DLEU1 was
      indispensible for the deposition of SMARCA1 at the promoter of KPNA3 gene.
      Increased expression of DLEU1 and KPNA3 was observed in human CRC tissues. And
      higher expression of DLEU1 or KPNA3 in patients indicates lower survival rate and
      poorer prognosis. DLEU1 knockdown remarkably inhibited CRC cell proliferation,
      migration and invasion in vitro and in vivo while overexpressing KPNA3 in the
      meantime reversed it. CONCLUSIONS: Our results identify DLEU1 as a key regulator
      by a novel DLEU1/SMARCA1/KPNA3 axis in CRC development and progression, which may
      provide a potential biomarker and therapeutic target for the management of CRC.

PMID- 30098596
TI  - Management of a case of high-risk gastrointestinal stromal tumor in rectum by
      transanal minimal invasive surgery.
AB  - BACKGROUND: Rectal gastrointestinal stromal tumor (GIST) is a very rare tumor of
      gastrointestinal tract. Surgical management of rectal GIST requires special
      attention for preserving of anal and urinary functions. Transanal minimal
      invasive surgery (TAMIS) is a well-developed minimally invasive technique for
      local excision of benign and early malignant rectal tumors; however, the
      application of TAMIS for rectal GIST is rarely and inadequately reported. We
      report the novel application of TAMIS for rectal GIST with considerations for
      anal and urinary functions. CASE PRESENTATION: A 67 years old female, who
      presented with history of per rectal bleeding, was diagnosed with submucosal GIST
      of 4.5 cm in diameter at right posterior wall of 7 cm from anal verge. Histology
      of biopsy showed abundant spindle-shaped cells arranged in bundles that were
      positive for CD34 and negative for C-Kit, desmin, smooth muscle actin (SMA), and
      S-100. The tumor was excised by TAMIS successfully. Final histopathology showed
      pT2 tumor with C-Kit positive and mitosis count 10 per 50 HPF. Postoperative
      period was uneventful, and she was discharged on adjuvant imatinib mesylate for 3
      years. CONCLUSION: TAMIS can be used safely in the management of rectal GIST
      after appropriate evaluation of tumor size, extent, location, and experience of
      operating surgeon.

PMID- 30098597
TI  - Retraction Note: The impact of repeated vaccination on influenza vaccine
      effectiveness: a systematic review and meta-analysis.
AB  - The authors have retracted this article, The impact of repeated vaccination on
      influenza vaccine effectiveness: a systematic review and meta-analysis.

PMID- 30098598
TI  - Reproductive aging and elective fertility preservation.
AB  - Reproductive aging is a natural process that occurs in all women, eventually
      leading to reproductive senescence and menopause. Over the past half century
      there has been a trend towards delayed motherhood. Postponing reproduction can
      increase the chance of a woman remaining involuntarily childless as well as an
      increase in pregnancy complications in those that do achieve pregnancy at
      advanced maternal age. Despite the well-documented decrease in fecundity that
      occurs as a woman ages, reproductive aged women frequently overestimate the age
      at which a significant decline in fertility occurs and overestimate the success
      of assisted reproductive technologies (ART) to circumvent infertility. Oocyte
      cryopreservation enables women to achieve genetically related offspring in the
      event that they desire to postpone their childbearing to an age after which a
      significant decline in fertility occurs or in circumstances in which their
      reproductive potential is compromised due to medical pathology. Available success
      rates and safety data following oocyte cryopreservation have been reassuring and
      is not considered experimental according to the American Society for Reproductive
      Medicine and the European Society for Human Reproduction and Embryology. This
      review article will focus on an evidence-based discussion relating to
      reproductive aging and oocyte cryopreservation.

PMID- 30098599
TI  - LncRNA PTAR promotes EMT and invasion-metastasis in serous ovarian cancer by
      competitively binding miR-101-3p to regulate ZEB1 expression.
AB  - BACKGROUND: Ovarian cancer (OvCa) is one of the most common malignant diseases of
      the female reproductive system in the world. The majority of OvCa is diagnosed
      with metastasis in the abdominal cavity. Epithelial-to-mesenchymal transition
      (EMT) plays a key role in tumor cell metastasis. However, it is still unclear
      whether long non-coding RNA (lncRNA) is implicated in EMT and influences cell
      invasion and metastasis in OvCa. RESULTS: In this study, using bioinformatcis
      analysis, we constructed a lncRNA-mediated competing endogenous RNA (ceRNA)
      network for mesenchymal OvCa and identified lncRNA AP000695.4, which we named pro
      transition associated RNA (PTAR). PTAR was significantly up-regulated in the
      mesenchymal subtype samples compared with the epithelial subtype samples from the
      TCGA OvCa data sets. In addition, our study showed that PTAR expression was
      positively correlated with the expression level of ZEB1 in the mesenchymal OvCa
      samples. Meanwhile, we found that silencing miR-101 promoted cell migration,
      whereas the overexpression of miR-101 suppressed EMT and cell migration in OvCa
      cell lines through the regulation of ZEB1. Further analysis showed that enhanced
      expression of PTAR promoted EMT and metastasis through the regulation of miR-101,
      whereas silencing PTAR led to the attenuation of TGF-beta1-induced tumorigenicity
      in ovarian cancer cells. Mechanistically, we found that PTAR acted as a ceRNA of
      miR-101, as forced expression of PTAR reduced the expression and activity of miR
      101. More importantly, the knockdown of PTAR reduced tumorigenicity and
      metastasis in vivo. CONCLUSIONS: Taken together, the results from our study
      highlight a role for the PTAR-miR-101-ZEB1 axis in OvCa, which offers novel
      strategies for the prevention of metastasis in OvCa.

PMID- 30098600
TI  - Role of hypoxia-induced exosomes in tumor biology.
AB  - PURPOSE: Hypoxia is a major regulator of angiogenesis and always influences the
      release of exosomes in various types of tumors. The present review aimed to
      assess the role of hypoxia-induced exosomes in the tumor biology. METHODS: The
      relevant publications were retrieved from PubMed using keywords such as hypoxia,
      exosome, extracellular vesicles, tumor, cancer, and other similar terms. RESULTS:
      Recent studies have shown that cancer cells produce more exosomes under hypoxic
      conditions than do parental cells under normoxic conditions. The secretion and
      function of exosomes could be influenced by hypoxia in various types of cancer.
      Hypoxia-induced exosomes play critical roles in tumor angiogenesis, invasion,
      metastasis, and the immune system. CONCLUSIONS: These findings provide new
      insights into the complex networks underlying cellular and genomic regulation in
      response to hypoxia and might provide novel and specific targets for future
      therapies.

PMID- 30098601
TI  - Characterization and high-efficiency secreted expression in Bacillus subtilis of
      a thermo-alkaline beta-mannanase from an alkaliphilic Bacillus clausii strain
      S10.
AB  - BACKGROUND: beta-Mannanase catalyzes the cleavage of beta-1,4-linked internal
      linkages of mannan backbone randomly to produce new chain ends. Alkaline and
      thermostable beta-mannanases provide obvious advantages for many applications in
      biobleaching of pulp and paper, detergent industry, oil grilling operation and
      enzymatic production of mannooligosaccharides. However, only a few of them are
      commercially exploited as wild or recombinant enzymes, and none heterologous and
      secretory expression of alkaline beta-mannanase in Bacillus subtilis expression
      system was reported. Alkaliphilic Bacillus clausii S10 showed high beta-mannanase
      activity at alkaline condition. In this study, this beta-mannanase was cloned,
      purified and characterized. The high-level secretory expression in B. subtilis
      was also studied. RESULTS: A thermo-alkaline beta-mannanase (BcManA) gene
      encoding a 317-amino acid protein from alkaliphilic Bacillus clausii strain was
      cloned and expressed in Escherichia coli. The purified mature BcManA exhibited
      maximum activity at pH 9.5 and 75  degrees C with good stability at pH 7.0-11.5
      and below 80  degrees C. BcManA demonstrated high cleavage capability on
      polysaccharides containing beta-1,4-mannosidic linkages, such as konjac
      glucomannan, locust bean gum, guar gum and sesbania gum. The highest specific
      activity of 2366.2 U mg-1 was observed on konjac glucomannan with the Km and kcat
      value of 0.62 g l-1 and 1238.9 s-1, respectively. The hydrolysis products were
      mainly oligosaccharides with a higher degree of polymerization than biose. BcManA
      also cleaved manno-oligosaccharides with polymerization degree more than 3
      without transglycosylation. Furthermore, six signal peptides and two strong
      promoters were used for efficiently secreted expression optimization in B.
      subtilis WB600 and the highest extracellular activity of 2374 U ml-1 with
      secretory rate of 98.5% was obtained using SPlipA and P43 after 72 h cultivation
      in 2 * SR medium. By medium optimization using cheap nitrogen and carbon source
      of peanut meal and glucose, the extracellular activity reached 6041 U ml-1 after
      72 h cultivation with 6% inoculum size by shake flask fermentation. CONCLUSIONS:
      The thermo-alkaline beta-mannanase BcManA showed good thermal and pH stability
      and high catalytic efficiency towards konjac glucomannan and locust bean gum,
      which distinguished from other reported beta-mannanases and was a promising
      thermo-alkaline beta-mannanase for potential industrial application. The
      extracellular BcManA yield of 6041 U ml-1, which was to date the highest reported
      yield by flask shake, was obtained in B. subtilis with constitutive expression
      vector. This is the first report for secretory expression of alkaline beta
      mannanase in B. subtilis protein expression system, which would significantly cut
      down the production cost of this enzyme. Also this research would be helpful for
      secretory expression of other beta-mannanases in B. subtilis.

PMID- 30098602
TI  - Does red blood cell irradiation and/or anemia trigger intestinal injury in
      premature infants with birth weight <= 1250 g? An observational birth cohort
      study.
AB  - BACKGROUND: Necrotizing enterocolitis (NEC) is a leading cause of neonatal
      morbidity and mortality in premature infants. To date, no effective biomarkers
      exist to predict which premature infants will develop NEC, limiting targeted
      prevention strategies. Multiple observational studies have reported an
      association between the exposure to red blood cell (RBC) transfusion and/or
      anemia and the subsequent development of NEC; however, the underlying physiologic
      mechanisms of how these factors are independently associated with NEC remain
      unknown. METHODS: In this paper, we outline our prospective, multicenter
      observational cohort study of infants with a birth weight <= 1250 g to
      investigate the associations between RBC transfusion, anemia, intestinal
      oxygenation and injury that lead to NEC. Our overarching hypothesis is that
      irradiation of RBC units followed by longer storage perturbs donor RBC metabolism
      and function, and these derangements are associated with paradoxical
      microvascular vasoconstriction and intestinal tissue hypoxia increasing the risk
      for injury and/or NEC in transfused premature infants with already impaired
      intestinal oxygenation due to significant anemia. To evaluate these associations,
      we are examining the relationship between prolonged irradiation storage time
      (pIST), RBC metabolomic profiles, and anemia on intestinal oxygenation non
      invasively measured by near-infrared spectroscopy (NIRS), and the development of
      NEC in transfused premature infants. DISCUSSION: Our study will address a
      critical scientific gap as to whether transfused RBC characteristics, such as
      irradiation and metabolism, impair intestinal function and/or microvascular
      circulation. Given the multifactorial etiology of NEC, preventative efforts will
      be more successful if clinicians understand the underlying pathophysiologic
      mechanisms and modifiable risk factors influencing the disease. TRIAL
      REGISTRATION: Our study is registered in ClinicalTrials.gov Identifier:
      NCT02741648 .

PMID- 30098603
TI  - Comparative study of endometrioid borderline ovarian tumor with and without
      endometriosis.
AB  - BACKGROUND: Synchronous endometriosis has been poorly studied in women with
      endometrioid borderline ovarian tumors (EBOTs). The aims of this study were to
      compare the clinicopathological features and prognosis of EBOTs with or without
      endometriosis. RESULTS: Of 52 patients diagnosed with EBOTs, no death was
      observed and only one case had successful pregnancy during the follow-up period.
      Older, menopausal EBOT patients, EBOT patients with small tumors and relatively
      low CA125 level probably had better progression-free survival (PFS) outcomes.
      About 1/3 of EBOTs had concomitant endometrial lesions. Approximately 1/3 of
      EBOTs were associated with endometriosis. Patients were divided into two groups
      according to the presence or not of endometriosis in this retrospective cohort
      study. Patients with endometriosis-associated endometrioid borderline ovarian
      tumor (EAEBOT) were more likely to be younger and premenopausal. Variables such
      as PFS outcomes, endometrial lesions did not differ statistically between groups.
      However, in specific EBOT patients like parous patients, patients with CA125 >=
      140 U/ml or patients without fertility sparing surgery, coexisting endometriosis
      perhaps predicted worse PFS outcomes. CONCLUSION: We considered EAEBOT as an
      entity similar to non-EAEBOT. Closely follow-up for some particular patients with
      concomitant endometriosis was necessary.

PMID- 30098605
TI  - Surgeon Scorecards: Accurate or Not?

PMID- 30098606
TI  - How to Predict 30-Day Readmission.

PMID- 30098607
TI  - Nipple-Sparing Mastectomy.

PMID- 30098604
TI  - K284-6111 prevents the amyloid beta-induced neuroinflammation and impairment of
      recognition memory through inhibition of NF-kappaB-mediated CHI3L1 expression.
AB  - BACKGROUND: Alzheimer's disease, which is pathologically characterized by an
      excessive accumulation of amyloid beta (Abeta) fibrils, is a degenerative brain
      disease and the most common cause of dementia. In a previous study, it was
      reported that an increased level of CHI3L1 in plasma was found in AD patients. We
      investigated the inhibitory effect of 2-({3-[2-(1-cyclohexen-1-yl)ethyl]-6,7
      dimethoxy-4-oxo-3,4-dihydro-2-quinazolinyl}sulfanyl)-N-(4-ethylphenyl)butanamide
      (K284-6111), an inhibitor of chitinase 3 like 1 (CHI3L1), on memory impairment in
      Abeta1-42-infused mice, and microglial BV-2 cells and astrocytes. METHODS: We
      examined whether K284-6111 (3 mg/kg given orally for 4 weeks) prevents
      amyloidogenesis and memory loss in Abeta1-42-induced AD mice model. After
      intracerebroventrical (ICV) infusion of Abeta1-42 for 14 days, the cognitive
      function was assessed by the Morris water maze test and passive avoidance test.
      K284-6111 treatment was found to reduce Abeta1-42-induced memory loss. RESULTS: A
      memory recovery effect was found to be associated with the reduction of Abeta1-42
      induced expression of inflammatory proteins (iNOS, COX-2, GFAP, and Iba-1) and
      the suppression of CHI3L1 expression in the brain. Additionally, K284-6111
      reduced Abeta1-42-induced beta-secretase activity and Abeta generation.
      Lipopolysaccharide (LPS)-induced (1 MUg/mL) expression of inflammatory (COX-2,
      iNOS, GFAP, Iba-1) and amyloidogenic proteins (APP, BACE1) were decreased in
      microglial BV-2 cells and cultured astrocytes by the K284-6111 treatment (0.5, 1,
      and 2 MUM). Moreover, K284-6111 treatment suppressed p50 and p65 translocation
      into the nucleus, and phosphorylation of IkappaB in vivo and in vitro.
      CONCLUSION: These results suggest that CHI3L1 inhibitor could be an applicable
      intervention drug in amyloidogenesis and neuroinflammation, thereby preventing
      memory dysfunction via inhibition of NF-kappaB.

PMID- 30098608
TI  - Should the Management of a Ruptured Abdominal Aortic Aneurysm Be Regionalized?

PMID- 30098609
TI  - Diagnosis and Management of Hyperparathyroidism.

PMID- 30098610
TI  - Laparoscopic Surgery for Small Bowel Obstruction: Is It Safe?

PMID- 30098611
TI  - Management of Aortoenteric Fistula.

PMID- 30098612
TI  - Benign Anorectal Surgery: Management.

PMID- 30098613
TI  - Intraperitoneal Drainage and Pancreatic Resection.

PMID- 30098614
TI  - How Long Should Patients with Cystic Lesions of the Pancreas Be Followed?

PMID- 30098616
TI  - Are Opioids Overprescribed Following Elective Surgery?

PMID- 30098615
TI  - What Is the Best Pain Control After Major Hepatopancreatobiliary Surgery?

PMID- 30098617
TI  - Contemporary Management of Critical Limb Ischemia.

PMID- 30098618
TI  - The Use of Lavage for the Management of Diverticulitis.

PMID- 30098619
TI  - Prevention and Treatment of Clostridium difficile Enterocolitis.

PMID- 30098620
TI  - The Management of Venous Thromboembolic Disease: New Trends in Anticoagulant
      Therapy.

PMID- 30098621
TI  - Proper Use of Cholecystostomy Tubes.

PMID- 30098622
TI  - Is Maintenance of Certification Working in Surgery?

PMID- 30098623
TI  - How Should Gallbladder Cancer Be Managed?

PMID- 30098624
TI  - Visual salience and biological motion interact to determine camouflaged target
      detectability.
AB  - Target visual salience and biological motion independently influence the accuracy
      and latency of observer detection. However, it is currently unknown how these
      target parameters might interact in modulating the detectability of camouflaged
      human targets. In two experiments, observers performed a visual target detection
      task. In a pilot experiment, observers detected a static human target with
      parametrically varied visual salience, superimposed on a complex background
      scene. As expected, results demonstrated varied target detectability as a
      function of salience, with observers showing higher hit rates and faster response
      times as a function of increased salience. In the Main Experiment, observers
      detected simulated human targets walking across a complex scene at five different
      speeds and three different levels of visual salience (as validated in the pilot
      experiment). We found strong effects of both movement rate and visual salience,
      and the two parameters interacted. Specifically, increasing the rate of
      biological motion increased detectability for even the least salient camouflage
      patterns. In other words, biological motion can "break" even the least
      conspicuous camouflage pattern. In contrast, a very salient pattern was highly
      detectable under static and moving conditions. Results are considered in relation
      to theories of camouflage detectability, and trade-offs between camouflage
      development efforts versus advanced training in military maneuvering.

PMID- 30098625
TI  - Selecting trainee pilots: Predictive validity of the WOMBAT situational awareness
      pilot selection test.
AB  - The WOMBAT pilot selection test is widely used to select candidates for pilot
      training programs. Despite use in many countries, little information is available
      regarding the predictive validity of the test. This study was designed to test
      the ability of the WOMBAT test to predict performance outcomes in a sample of ab
      initio pilots. Sixty students commenced the study in 3 cohorts, and completed the
      WOMBAT test before their performance in the training program was evaluated
      through flight time to solo, flight time to licence level achievement, and
      instructor ratings of performance. Higher WOMBAT total scores were significantly
      related to reduced time to solo, achieving flight licences, as well as some early
      ratings of performance by flight instructors. Further research now needs to
      examine the exact nature of the skills and abilities that the test indexes in
      order to further improve pilot selection and training procedures.

PMID- 30098626
TI  - Beyond ConCA: Rethinking causality and construction accidents.
AB  - The construction industry takes an orthodox approach to safety: Finding root
      causes, quantifying risk, and often blaming frontline workers. However, safety
      has reached a plateau and the limitations of this approach are starting to be
      acknowledged. A sociotechnical systems approach (as applied in the ConCA model)
      presents new opportunities to understand accident causation by linking immediate
      accident circumstances with the distal shaping and originating influences. 32
      construction safety managers, consultants, and experts contributed their views
      regarding the hazards of construction (both human and physical) and the
      difficulties managing these. The findings provide an insight into the work of
      construction safety managers and their decision making which is influenced by
      industry-wide pressures and worker attributes over physical hazards. Construction
      suffers from a wide range of pressures; a combination of both top-down, from the
      client, and bottom-up challenges from the workforce it attracts. The original
      ConCA model has been revised to reflect the findings. By applying systems
      thinking, the relationships between negative perceptions of workers' risk-taking
      and these challenges can be crystallised. The results support integrating safety
      into primary activities to increase engagement, learning legacies to transfer
      knowledge between projects, multi-disciplinary teams to raise risk awareness,
      empowerment to combat their feelings of dissatisfaction and disloyalty, and
      collaboration in risk management to incorporate workers' expertise and ensure
      they feel valued.

PMID- 30098627
TI  - Barriers for implementation of successful change to prevent musculoskeletal
      disorders and how to systematically address them.
AB  - This scoping review identified common barriers and facilitators encountered
      during the implementation of changes to prevent musculoskeletal disorders (MSD)
      and examined their relationship with those encountered in general Occupational
      Health and Safety (OHS) efforts. Thematic analysis of the literature identified
      11 barriers: (i) Lack of time; (ii) Lack of resources; (iii) Lack of
      communication; (iv) Lack of management support, commitment, and participation;
      (v) Lack of knowledge and training; (vi) Resistance to change; (vii) Changing
      work environment; (viii) Scope of activities; (ix) Lack of trust, fear of job
      loss, or loss of authority; (x) Process deficiencies; and (xi) Difficulty of
      implementing controls. Three facilitators identified were: (i) Training,
      knowledge and ergonomists' support; (ii) Communication, participation and
      support; and (iii) An effective implementation process. The barriers and
      facilitators identified were similar to those in general OHS processes. The
      integration of MSD prevention into a general management system approach may
      overcome these barriers.

PMID- 30098629
TI  - Relocation to an activity-based flexible office - Design processes and outcomes.
AB  - Many organizations relocate to activity-based flexible offices (A-FOs) and the
      results are mixed. This study aims at identifying factors in the design and
      implementation process that contribute to perceived performance and environmental
      satisfaction with A-FOs. A company with 50 employees was studied using
      interviews, questionnaires and documentation before and after relocation. The
      results showed that process factors such as objectives, financial and time
      resources, employee participation and empowerment, and methodological approach
      contributed to the outcomes. Perceived performance and employee satisfaction with
      the physical environment increased significantly after the relocation. Employee
      empowerment, highlighted by the employees, correlated with the performance and
      satisfaction parameters. A conceptual model is proposed relating process factors,
      internal and external organizational context, and physical office setting to work
      condition consequences and overall outcomes such as employee performance and
      satisfaction.

PMID- 30098628
TI  - Effects of seat parameters and sitters' anthropometric dimensions on seat profile
      and optimal compressed seat pan surface.
AB  - Designing one seat for multi-sitters and multi-activities is challenging
      especially in a very restrained aircraft economy class cabin. In this paper, the
      effects of seat parameters and sitters' anthropometric dimensions on seat profile
      and optimal compressed seat pan surface were studied using a newly built multi
      adjustable experimental seat. The 'optimal' seat pan contact surface was obtained
      by controlling the height of 52 cylinders so that the normal contact force was
      distributed to all cylinders as evenly as possible. With 13 other motorized
      adjustments controllable by a computer, individual seat profile in the symmetry
      plane such as seat height, seat pan length, seat pan angle, lumbar protrusion and
      headrest position were also studied. Data were collected from 36 men and women of
      varying body size testing 40 seat configurations. Parametric models were obtained
      for predicting seat profile and optimal compressed seat pan seat surface in
      function of seat pan and back rest angles for two sitting postures. It is
      expected that the proposed parametric models provide necessary reference values
      in seat development for a better fit of a target population of sitters with large
      varying body size.

PMID- 30098630
TI  - Human performance measures for the evaluation of process control human-system
      interfaces in high-fidelity simulations.
AB  - We reviewed the available literature on measuring human performance to evaluate
      human-system interfaces (HSIs), focused on high-fidelity simulations of
      industrial process control systems, to identify best practices and future
      directions for research and operations. We searched the available literature and
      then conducted in-depth review, structured coding, and analysis of 49 articles,
      which described 42 studies. Human performance measures were classified across six
      dimensions: task performance, workload, situation awareness,
      teamwork/collaboration, plant performance, and other cognitive performance
      indicators. Many studies measured performance in more than one dimension, but few
      studies addressed more than three dimensions. Only a few measures demonstrated
      acceptable levels of reliability, validity, and sensitivity in the reviewed
      studies in this research domain. More research is required to assess the
      measurement qualities of the commonly used measures. The results can provide
      guidance to direct future research and practice for human performance measurement
      in process control HSI design and deployment.

PMID- 30098631
TI  - Corrigendum to "A method for effect modifier assessment (EMA) in ergonomic
      intervention research" [Appl. Ergon. 72, (October 2018), 113-120].

PMID- 30098632
TI  - Detection of visual stimuli on monocular peripheral head-worn displays.
AB  - OBJECTIVE: To compare people's ability to detect peripherally presented stimuli
      on a monocular head-worn display (HWD) versus a conventional screen. BACKGROUND:
      Visual attention capture has been systematically investigated, but not with
      respect to HWDs. How stimulus properties affect attention capture is likely to be
      different on an HWD when compared to a traditional computer display. METHOD:
      Participants performed an ongoing perceptual task and attempted to detect stimuli
      that were displayed peripherally on either a computer monitor or a monocular HWD.
      RESULTS: Participants were less able to detect peripheral stimuli when the
      stimuli were presented on a HWD than when presented on a computer monitor.
      Moreover, the disadvantage of the HWD was more pronounced when peripheral stimuli
      were less distinct and when the stimuli were presented further into the
      periphery. CONCLUSION: Presenting stimuli on a monocular head-worn display
      reduces participants' ability to notice peripheral visual stimuli compared to
      presentation on a normal computer monitor. This effect increases as stimuli are
      presented further in the periphery, but can be ameliorated to a degree by using
      high-contrast stimuli. APPLICATION: The findings are useful for designers
      creating visual stimuli intended to capture attention when viewed on a
      peripherally positioned monocular head-worn display.

PMID- 30098633
TI  - Inattentional blindness and pattern-matching failure: The case of failure to
      recognize clinical cues.
AB  - Eye-tracking methodology was used to investigate lapses in the appropriate
      treatment of ward patients due to not noticing critical cues of deterioration.
      Forty nursing participants with different levels of experience participated in an
      interactive screen-based simulation of hypovolemic shock. The results show that
      65% of the participants exhibited at least one episode of non-fixation on
      clinically relevant, fully visible cues that were in plain sight. Thirty-five
      percent of participants dwelt for sufficient time (>200 ms) on important cues for
      perception to take place, but no action followed, indicating they had pattern
      matching failure. When participants fail to notice what, they should notice in
      patient status until it is too late, this can have serious consequences. Much
      work needs to be done, since these human perceptual limitations can affect
      patient safety in general wards.

PMID- 30098634
TI  - Glance behavior as design indices of in-vehicle visual support system: A study
      using crane simulators.
AB  - A prediction model is used to predict subjective responses of crane operators
      with respect to different designs of In-Vehicle Visual Support (IVVS). Selected
      gaze metrics are used as objective metrics to minimize prejudice, which is
      commonly caused by subjective measures. Experiments are carried out using crane
      simulator to measure glance behavior of novice operators and the 3D perspective
      projection method is used for autonomous mapping of gaze fixations to dynamic
      Area-of-Interests (AOIs). Subjective responses, such as operators' emotion and
      usability of IVVS, are evaluated using the Likert scale of the Semantic
      Differential method. Correlation between gaze metrics and subjective responses is
      established using multiple linear regression. Glance behavior exhibits a
      statistically significant difference when information on IVVS is perceived as
      useful to ease operation and reduce tension. Despite this, there are no
      significant signs of distraction. Glance behavior is found to be a reliable sub
      conscious indicator of subjective response and distraction. More importantly, the
      proposed gaze metrics are found to be a good representation of glance behavior,
      such as randomness and distribution of attention. The methods and findings are
      useful to evaluate impact of IVVS, which is becoming more common in many other
      applications.

PMID- 30098636
TI  - Spatial dependency of shoulder muscle demand during dynamic unimanual and
      bimanual pushing and pulling.
AB  - Work involving extensive pushing and pulling is associated with higher frequency
      of shoulder complaints. While reports of shoulder muscle demand during submaximal
      isometric tasks are abundant, dynamic submaximal push-pull exertions are not well
      understood. We evaluated how muscle demand (weighted EMG average) of surface
      glenohumeral muscles varies with task type and target. Seventeen healthy young
      adults performed seated unimanual and bimanual pushes and pulls to 3
      thoracohumeral elevations (20 degrees , 90 degrees , 170 degrees ) and 4
      elevation planes (0 degrees , 45 degrees , 90 degrees , 135 degrees ) with
      loading at 15% of isometric push-pull capacity. Pulling required less demand than
      pushing (p < 0.0001). Muscle demand varied more with elevation than elevation
      plane. The lowest target had highest demand for pulling (p < 0.01), and the most
      elevated target had highest demand for pushing (p < 0.0001). Working above the
      shoulder is known to increase demand during isometric tasks, however, these
      results suggest that for dynamic tasks working against gravity has a larger
      effect on demand than task target.

PMID- 30098635
TI  - Cardiorespiratory responses to heavy military load carriage over complex terrain.
AB  - This study examined complex terrain march performance and cardiorespiratory
      responses when carrying different Soldier loads. Nine active duty military
      personnel (age, 21 +/- 3 yr; height, 1.72 +/- 0.07 m; body mass (BM), 83.4 +/-
      12.9 kg) attended two test visits during which they completed consecutive laps
      around a 2.5-km mixed terrain course with either a fighting load (30% BM) or an
      approach load (45% BM). Respiratory rate and heart rate data were collected using
      physiological status monitors. Training impulse (TRIMP) scores were calculated
      using Banister's formula to provide an integrated measure of both time and
      cardiorespiratory demands. Completion times were not significantly different
      between the fighting and approach loads for either Lap 1 (p = 0.38) or Lap 2 (p =
      0.09). Respiration rate was not significantly higher with the approach load than
      the fighting load during Lap 1 (p = 0.17) but was significantly higher for Lap 2
      (p = 0.04). However, heart rate was significantly higher with the approach load
      versus the fighting load during both Lap 1 (p = 0.03) and Lap 2 (p = 0.04).
      Furthermore, TRIMP was significantly greater with the approach load versus the
      fighting load during both Lap 1 (p = 0.02) and Lap 2 (p = 0.02). Trained military
      personnel can maintain similar pacing while carrying either fighting or approach
      loads during short mixed terrain marches. However, cardiorespiratory demands are
      greatly elevated with the approach load and will likely continue to rise during
      longer distance marches.

PMID- 30098638
TI  - From the seat to the system: Re-designing a tram drivers' workstation combining
      technical and contextual aspects.
AB  - Through the detailed account of a design case-study, the paper aims to
      demonstrate how the activity-oriented approach promotes a systems perspective in
      ergonomics interventions. Specifically, by presenting an activity-oriented re
      design of a tram drivers' workstation, it is shown: (i) how technical and
      contextual aspects were jointly considered, (ii) how their combination affects
      workers' activity in a non-trivial manner, and (iii) how this system level view
      helped generate feasible and sustainable design solutions. First, the activity
      oriented theoretical lens is briefly presented, followed by the analysis of the
      tram driving activity, emphasizing on drivers' efforts to compensate for the
      original work-system design flaws. Next, key elements of the re-design process
      are presented, through a concept map, combining technical and contextual aspects,
      coupled with an account of stakeholder debates and resolution processes. The
      paper ends with a discussion on the lessons learned, concerning the adopted
      approach for design interventions in real work situations.

PMID- 30098637
TI  - Workstation configuration and container type influence upper limb posture in
      grocery bagging.
AB  - INTRODUCTION: Repetitive movements and awkward postures are two persistent injury
      risk factors for grocery store cashiers. Due to the recent rise in popularity of
      environmentally-friendly grocery bagging options, current recommendations for
      cashiers are likely outdated. Correspondingly, the objective of this study was to
      examine the effects of cashier-specific work demands, workstation configuration,
      and container type on upper limb postures during typical job activities. METHODS:
      Fifteen experienced cashiers bagged groceries at varying combinations of
      workstation height (low, medium, high) and container type (reusable bins,
      reusable bags, plastic bags). Upper limb movement was quantified with motion
      capture and amplitude probability distribution functions of humeral elevation and
      humeral axial internal rotation were used to assess the static (10th percentile),
      median (50th percentile), and peak (90th percentile) postural demands, which were
      then interpreted in the context of existing postural guidelines. RESULTS: High
      workstation height and reusable bags increased right arm elevation at peak
      posture by 15.7 degrees  compared to the low workstation height and reusable bin
      combination. However, reusable bins increased internal rotation demands of the
      right arm by 4.3 degrees  compared to other container types. Left arm elevation
      and internal rotation were consistently lower than right arm angles. CONCLUSION:
      Cashiers are encouraged to adjust the workstation to decrease the arm elevation
      and internal rotation required by higher workstation heights and tall containers,
      and to use both arms for scanning and packing, when possible, to reduce
      undesirable arm postures.

PMID- 30098639
TI  - Comparative usability evaluation of consultation order templates in a simulated
      primary care environment.
AB  - Communication breakdowns in the referral process negatively impact clinical
      workflow and patient safety. There is a lack of evidence demonstrating the impact
      of published design recommendations addressing contributing issues with
      consultation order templates. This study translated the recommendations into a
      computer-based prototype and conducted a comparative usability evaluation. With a
      scenario-based simulation, 30 clinicians (referrers) participated in a within
      group, counterbalanced experiment comparing the prototype with their present
      electronic order entry system. The prototype significantly increased satisfaction
      (Cohen's d = 1.80, 95% CI [1.19, 2.41], p < .001), and required significantly
      less mental effort (d = 0.67 [0.14, 1.20], p < .001). Regarding efficiency, the
      prototype required significantly fewer mouse clicks (mean difference = 29 clicks,
      p < .001). Although overall task time did not differ significantly (d = -0.05 [
      0.56, 0.47]), the prototype significantly quickened identification of the
      appropriate specialty clinic (mean difference = 12 s, d = 0.98 [0.43, 1.52], p <
      .001). The experimental evidence demonstrated that clinician-centered interfaces
      significantly improved system usability during ordering of consultations.

PMID- 30098640
TI  - Clothing comfort during physical exercise - Determining the critical factors.
AB  - Clothing comfort is determined by multiple material and design factors. Wetness
      at the skin-clothing interface mainly impacts wear comfort. The current study
      investigated the combined effect of fabric contact area, fabric absolute sweat
      content and fabric moisture saturation percentage on wetness and stickiness
      sensations, during exercise. Moreover, factors causing wear (dis)comfort during
      exercise were identified. Higher fabric saturation percentage induced greater
      stickiness sensation, despite lower fabric contact area and absolute sweat
      content (typically associated with lower stickiness). Wetness perception did not
      change between fabrics with different saturation percentages, contact areas and
      sweat contents. Therefore, fabric saturation percentage mainly affects stickiness
      sensation of wet fabrics, overruling the impact of fabric contact area and
      absolute sweat content. No overall model of wear discomfort across all data could
      be developed, however, models for different time points were produced, with
      texture and stickiness sensations being the best predictors of wear discomfort at
      baseline and during exercise, respectively. This suggests that the factors
      determining clothing (dis)comfort are dynamics and alter importance during
      exercise activity.

PMID- 30098641
TI  - Bio-mathematical fatigue models predict sickness absence in hospital nurses: An
      18 months retrospective cohort study.
AB  - This study examined the associations between bio-mathematical fatigue-risk scores
      and sickness absence (SA) in hospital nurses over 18 months. Work schedules and
      SA data were extracted from the hospital's attendance system. Fatigue-risk scores
      were generated for work days using the Fatigue Audit InterDyne (FAID) and Fatigue
      Risk Index (FRI). Over the study period, 5.4% of the shifts were absence shifts.
      FAID-fatigue ranged from 7 to 154; scores for a standard 9-5 work schedule can
      range from 7 to 40. Nurses with high FAID-scores were more likely to be absent
      from work when compared to standard FAID-scores (41-79, OR = 1.38, 95%CI = 1.21
      1.58; 80-99, OR = 1.63, 95%CI = 1.37-1.94 and >= 100, OR = 1.73, 95%CI = 1.40
      2.13). FRI-fatigue ranged from 0.9 to 76.8. When FRI-scores were >60, nurses were
      at 1.58 times (95%CI = 1.05-2.37) at increased odds for SA compared to scores in
      the 0.9-20 category. Nurse leaders can use these decision-support models to
      adjust high-risk schedules or the number of staff needed to cover anticipated
      absences from work.

PMID- 30098642
TI  - Armrests and back support reduced biomechanical loading in the neck and upper
      extremities during mobile phone use.
AB  - Mobile phone use is known to be associated with musculoskeletal pain in the neck
      and upper extremities because of related physical risk factors, including awkward
      postures. A chair that provides adequate support (armrests and back support) may
      reduce biomechanical loading in the neck and shoulder regions. Therefore, we
      conducted a repeated-measures laboratory study with 20 participants (23 +/- 1.9
      years; 10 males) to determine whether armrests and back support during mobile
      phone use reduced head/neck flexion, gravitational moment, and muscle activity in
      the neck and shoulder regions. The results showed that the chair support
      (armrests and back support) reduced head/neck flexion (p < 0.001), gravitational
      moment (p < 0.001), and muscle activity (p < 0.01) in the neck and shoulder
      regions significantly compared to no chair support. These results indicate that a
      chair with adequate support can be an effective intervention to reduce the
      biomechanical exposures and associated muscular pain in the neck and shoulders
      during mobile phone use.

PMID- 30098643
TI  - Production quality and human factors engineering: A systematic review and
      theoretical framework.
AB  - The purpose of this paper is to systematically examine available empirical
      evidence on the impact of human factors (HF) in the design and management of
      manufacturing operations on system quality performance. A systematic review was
      conducted to map the linkages between the human-system fit in the design of
      operations systems (OS) with production quality. A total of 73 empirical studies
      were identified linking HF to OS performance in manufacturing. Quality risk
      factors included HF aspects in product design, process design and workstation
      design of the manufacturing OS. Quality deficits were associated with undesirable
      human effects of workload like fatigue and injury-related risk factors. Forty-six
      percent of the studies reported on efforts to improve HF in the OS with effect
      sizes for quality improvements reaching up to 86%. The paper documents available
      quality risk factors in the design of OS. It also provides a conceptual framework
      explaining HF-Quality linkage.

PMID- 30098644
TI  - Effect of in-seat exercising on comfort perception of airplane passengers.
AB  - Sitting still for extended periods of time can lead to physical discomfort and
      even serious health risks. Due to safety regulations, reducing passenger' sitting
      time in aircrafts is not feasible. This paper presents the results of a
      laboratory study, in where an interactive airplane seat was compared with a
      current economy class seat. Participants used both seats for 3.5 h, and performed
      significantly more in-seat movements when using the interactive seating system.
      Furthermore, this interactive seat predominantly lead to significantly better
      comfort experiences and reduced discomfort experiences, however no significant
      differences have been found in self-reported localized musculoskeletal
      discomfort. Passengers indicated that they would prefer this interactive seat
      over a standard aircraft seat.

PMID- 30098645
TI  - Mental workload is reflected in driver behaviour, physiology, eye movements and
      prefrontal cortex activation.
AB  - Mental workload is an important factor during driving, as both high and low
      levels may result in driver error. This research examined the mental workload of
      drivers caused by changes in road environment and how such changes impact upon
      behaviour, physiological responses, eye movements and brain activity. The
      experiment used functional near infrared spectroscopy to record prefrontal cortex
      activation associated with changes in mental workload during simulated driving.
      Increases in subjective ratings of mental workload caused by changes in road type
      were accompanied by increases in skin conductance, acceleration signatures and
      horizontal spread of search. Such changes were also associated with increases in
      the concentration of oxygenated haemoglobin in the prefrontal cortex. Mental
      workload fluctuates during driving. Such changes can be identified using a range
      of measures which could be used to inform the development of in-vehicle devices
      and partially autonomous systems.

PMID- 30098646
TI  - Interventional Equipment and Radiation Safety.
AB  - Interventional radiology in veterinary medicine was adapted from techniques
      developed in human medicine, and has a variety of applications to treat disease
      in multiple body systems. Fluoroscopy is required for almost all interventional
      procedures, requiring knowledge of proper safety techniques for working with
      ionizing radiation. There are a wide variety of catheters, wires, sheaths,
      stents, and embolics used in veterinary medicine. Familiarity with their
      indications and sizing compatibility is essential for procedural success.

PMID- 30098647
TI  - Minimally Invasive Management of Uroliths in Cats and Dogs.
AB  - Urolithiasis commonly affects cats and dogs. The American College of Veterinary
      Internal Medicine established guidelines for the treatment of uroliths that
      reflect modern techniques prioritizing minimally invasive procedures with an
      emphasis on prevention strategies to limit morbidity and mortality.
      Extracorporeal shockwave lithotripsy and endoscopic nephrolithotomy constitute
      some of the minimally invasive treatment modalities available for upper urinary
      tract uroliths. Cystoscopic-guided basket retrieval, cystoscopic-guided laser
      lithotripsy, and percutaneous cystolithotomy are minimally invasive options for
      the management of lower urinary tract uroliths. Following stone removal,
      prevention strategies are essential to help reduce morbidity and mortality
      associated with stone recurrence.

PMID- 30098648
TI  - Pharmacokinetics, Tolerability, and Bioequivalence of Two Formulations of
      Rotigotine in Healthy Chinese Subjects.
AB  - PURPOSE: The pharmacokinetic (PK) profile of the rotigotine transdermal patch is
      well characterized in Caucasian patients with Parkinson's disease (PD) but not in
      Chinese subjects. This article reports the PK variables, safety, and tolerability
      of the rotigotine transdermal patch (2 mg/24 hours and 4 mg/24 hours cold-chain
      PR2.1.1 formulation) in healthy Chinese subjects (SP0913; NCT01675024). A second
      study (PD0011; NCT02070796) evaluated the relative bioavailability of cold-chain
      (PR2.1.1) and room temperature-stable (PR2.2.1) formulations of rotigotine in
      healthy Chinese men. METHODS: In treatment period 1 of SP0913, subjects received
      a single application of rotigotine 2 mg/24 hours on day 1 followed by a washout
      period (days 2-6); treatment period 2 (days 6-14) involved multiple doses of
      rotigotine 2 mg/24 hours (days 7-9) followed by multiple doses of rotigotine 4
      mg/24 hours (days 10-12), with patches applied for 24 hours each. In PD0011,
      subjects received a single dose (2 mg/24 hours) of each rotigotine formulation
      (PR2.2.1 and PR2.1.1) for 24 hours each in a crossover design. Blood samples were
      collected at scheduled time points to determine rotigotine plasma concentrations.
      Safety and tolerability were evaluated by adverse events monitoring. RESULTS:
      Twenty-four healthy Chinese subjects (12 males, 12 females) were enrolled and
      completed SP0913. Geometric mean plasma concentrations of unconjugated and total
      rotigotine increased to a plateau beginning at ~8 hours (multiple dose) to 16
      hours (single dose) postdose; no characteristic Tmax was observed for
      unconjugated and total rotigotine. The respective geometric mean Cmax, Cmax,ss,
      AUC from zero up to the last analytically quantifiable concentration, and AUC0
      24,ss values for unconjugated and total rotigotine were similar when rotigotine 2
      mg/24 hours was applied as a single dose or multiple-dose regimen. During the
      multiple-dose period, geometric mean Cmax,ss and AUC0-24,ss of both unconjugated
      and total rotigotine were ~2-fold higher for rotigotine 4 mg/24 hours than for
      rotigotine 2 mg/24 hours. Forty-seven of 50 male Chinese subjects completed
      PD0011. Primary PK parameters for the room temperature-stable formulation of
      rotigotine were highly comparable to the cold-chain formulation. Common adverse
      events included application site pruritus, nausea, dizziness, and constipation
      (SP0913 only), with no clinically significant changes in other safety measures.
      IMPLICATIONS: PK profiles and derived PK parameters of unconjugated and total
      rotigotine in healthy Chinese subjects were consistent with findings from other
      ethnic groups receiving single and multiple doses of the rotigotine transdermal
      patch. Single and repeated daily doses of the rotigotine transdermal patch were
      well tolerated. Room temperature-stable and cold-chain formulations were
      bioequivalent. ClinicalTrials.gov identifiers: NCT01675024 and NCT02070796.

PMID- 30098649
TI  - Electroconvulsive Therapy in Depression: Current Practice and Future Direction.
AB  - The current practice of electroconvulsive therapy (ECT) has evolved over several
      decades with the implementation of safer equipment and advancement of techniques.
      In addition, modifications in the delivery of ECT, such as the utilization of
      brief and ultrabrief pulse widths and individualization of treatment parameters,
      have improved the safety of ECT without sacrificing efficacy. This article aims
      to provide psychiatrists with a balanced, in-depth look into the recent advances
      in ECT technique as well as the evidence of ECT for managing depression in
      special populations and patients with comorbid medical problems.

PMID- 30098650
TI  - When All Else Fails: The Use of Electroconvulsive Therapy for Conditions Other
      than Major Depressive Episode.
AB  - The use of electroconvulsive therapy (ECT) for those suffering from major
      depressive disorder is well-evidenced, time-honored, and recognized by most
      treatment guidelines. However, since its inception ECT has been used by
      practitioners for a broader range of neuropsychiatric conditions. This article
      reviews the highly variable evidence supporting the use of ECT in conditions
      other than depression, such as schizophrenia, bipolar manic states, catatonia,
      Parkinson disease, and post-traumatic stress disorder.

PMID- 30098652
TI  - Deep Brain Stimulation: Clinical Applications.
AB  - Deep brain stimulation has been used for decades in neurology to treat movement
      disorders. More recent work has focused on developing applications for deep brain
      stimulation in psychiatric illness. Initial studies have demonstrated positive
      results for treatment-refractory obsessive-compulsive disorder. Initial open
      label studies of deep brain stimulation at targets for treatment-resistant
      depression have been encouraging. However, the only 2 published controlled trials
      that were conducted for potential FDA approval for treatment-resistant depression
      were both negative. Future directions include potential use of alternate clinical
      trial designs, using tractography for more refined deep brain stimulation
      electrode targeting, and closed-loop deep brain stimulation approaches.

PMID- 30098653
TI  - The Mechanism of Action of Vagus Nerve Stimulation in Treatment-Resistant
      Depression: Current Conceptualizations.
AB  - Stimulation of the left cervical vagus nerve, or vagus nerve stimulation (VNS),
      brings about an antidepressant response in a subset of treatment-resistant
      depression (TRD) patients. How this occurs is poorly understood; however,
      knowledge of the neuroanatomic vagal pathways, in conjunction with functional
      brain imaging studies, suggests several brain regions associated with mood
      regulation are critical: brainstem nuclei (locus coeruleus, dorsal raphe, and
      ventral tegmental area), thalamus, and insular and prefrontal cortex.
      Furthermore, animal studies suggest that VNS enhances neuroplasticity and changes
      in neuronal firing patterns. Continued study to better understand the mechanism
      of action of VNS in TRD is warranted.

PMID- 30098654
TI  - Vagus Nerve Stimulation: Changing the Paradigm for Chronic Severe Depression?
AB  - Vagus nerve stimulation (VNS) has been studied for its effect on treatment
      resistant depression. Open-label studies have shown a significant positive effect
      in an especially treatment-resistant depressive population. Insurance company
      support for VNS has been limited but may be reviewed given recent positive open
      label data. Coming developments in novel external ways to stimulate the vagus
      nerve may revive interest in this area. This article reviews the clinical
      development of VNS starting with the first recognition of its potential for
      treating depression, parses the results of several large clinical trials, and
      suggests a future path for optimal clinical development and use.

PMID- 30098651
TI  - Deep Brain Stimulation in Psychiatry: Mechanisms, Models, and Next-Generation
      Therapies.
AB  - Deep brain stimulation has preliminary evidence of clinical efficacy, but has
      been difficult to develop into a robust therapy, in part because its mechanisms
      are incompletely understood. We review evidence from movement and psychiatric
      disorder studies, with an emphasis on how deep brain stimulation changes brain
      networks. From this, we argue for a network-oriented approach to future deep
      brain stimulation studies. That network approach requires methods for identifying
      patients with specific circuit/network deficits. We describe how dimensional
      approaches to diagnoses may aid that identification. We discuss the use of
      network/circuit biomarkers to develop self-adjusting "closed loop" systems.

PMID- 30098655
TI  - Updates on Transcranial Magnetic Stimulation Therapy for Major Depressive
      Disorder.
AB  - Transcranial magnetic stimulation has emerged as a treatment option for treatment
      resistant depression. While existing data largely support efficacy of
      transcranial magnetic stimulation for major depressive disorder, ongoing research
      aims to optimize treatment parameters and identify biomarkers of treatment
      response. In this article, the authors describe data from controlled trials and
      ongoing efforts to enhance transcranial magnetic stimulation outcomes for major
      depressive disorder. Findings from preliminary research aimed at identifying
      neuroimaging and neurophysiological biomarkers of transcranial magnetic
      stimulation effects are discussed.

PMID- 30098656
TI  - Clinical Repetitive Transcranial Magnetic Stimulation for Posttraumatic Stress
      Disorder, Generalized Anxiety Disorder, and Bipolar Disorder.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is being investigated for
      psychiatric disorders such as posttraumatic stress disorder (PTSD), generalized
      anxiety disorder (GAD), and both phases of bipolar disorder. Case series, open
      trials, and randomized controlled studies have demonstrated preliminary support
      for treating PTSD with rTMS alone as well as with rTMS combined with
      psychotherapy. Similarly, there is some evidence that GAD can be treated with
      rTMS. The results for treating either phase of bipolar disorder are mixed with
      most of the current studies showing lack of benefit over sham. Further study is
      required before rTMS can be recommended for these disorders.

PMID- 30098657
TI  - Transcranial Direct Current Stimulation in Psychiatric Disorders: A Comprehensive
      Review.
AB  - Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation
      technique that has been gaining favor as a viable tool in Psychiatry. The purpose
      of this review is to summarize the evidence of tDCS as a treatment of disorders
      such as depression, schizophrenia, and obsessive-compulsive disorder (OCD).
      Current findings indicate that tDCS is probably effective in non-treatment
      resistant depressive patients. Regarding schizophrenia and OCD, present evidence
      is not robust enough, although preliminary results indicate that tDCS is a
      promising technique. Therefore, more trials are needed before using tDCS in a
      clinical setting.

PMID- 30098658
TI  - Therapeutic Applications of Noninvasive Neuromodulation in Children and
      Adolescents.
AB  - Recent advances and growing evidence supporting the safety and efficacy of
      noninvasive neuromodulatory techniques in adults have facilitated the study of
      neuromodulation applications in children and adolescents. Noninvasive brain
      stimulation methods such as transcranial direct current stimulation and
      transcranial magnetic stimulation have been considered in children with
      depression, autism spectrum disorder, attention-deficit hyperactivity disorder,
      and other neuropsychiatric disorders. However, current clinical applications of
      neuromodulation techniques in children and adolescents are nascent. There is a
      great need for developmentally informed, large, double-blinded, randomized,
      controlled clinical trials to demonstrate efficacy and safety of noninvasive
      brain stimulation in children and adolescents.

PMID- 30098660
TI  - Clinical Usefulness of Therapeutic Neuromodulation for Major Depression: A
      Systematic Meta-Review of Recent Meta-Analyses.
AB  - The authors conducted a meta-review of meta-analyses published in the past decade
      on therapeutic neuromodulation (ie, repetitive transcranial magnetic stimulation,
      transcranial direct current stimulation, vagus nerve stimulation and deep brain
      stimulation) for major depression. Active repetitive transcranial magnetic
      stimulation and transcranial direct current stimulation have been generally
      associated with small to moderate effect sizes vis-a-vis their efficacy and with
      similar acceptability compared with sham. Vagus nerve stimulation and deep brain
      stimulation (although more challenging to investigate) have demonstrated
      preliminary effectiveness, particularly during longer-term follow-up.

PMID- 30098659
TI  - Therapeutic Applications of Invasive Neuromodulation in Children and Adolescents.
AB  - Although the application of noninvasive brain stimulation methods to children and
      adolescents has been frequently studied in depression, autism spectrum disorder,
      attention-deficit/hyperactivity disorder, and other neuropsychiatric disorders,
      invasive methods such as deep brain stimulation (DBS) and vagal nerve stimulation
      (VNS) have received less attention. DBS and VNS have demonstrated utility in
      young patients especially for dystonia and epilepsy. VNS has FDA clearance for
      intractable epilepsy in patients aged 4 years and older. Further measured work
      with invasive neuromodulation for children and adolescents with debilitating
      neuropsychiatric disorders could provide new treatment options and expand current
      knowledge base of neurocircuitry across development.

PMID- 30098661
TI  - Noninvasive Focused Ultrasound for Neuromodulation: A Review.
AB  - This article covers noninvasive focused ultrasound (FUS) and its potential for
      neuromodulation. Although diagnostic uses of ultrasound are well known, its
      potential to noninvasively alter brain activity is a relatively new subject of
      research. Low-intensity focused ultrasound (LIFU) is a potential future
      alternative modality to other noninvasive neuromodulation techniques. This
      article aims at providing an updated review of the literature related to the role
      of LIFU in neuromodulation and the progress of animal as well as human research
      done on this topic. It also includes a critical review of the safety concerns
      slowing the translation of LIFU research into clinical trials.

PMID- 30098662
TI  - The Future of Brain Stimulation Treatments.
AB  - Trends in brain stimulation include becoming less invasive, more focal, and more
      durable with less toxicity. Several of the more interesting new potentially
      disruptive technologies that are just making their way through basic and
      sometimes clinical research studies include low-intensity focused ultrasound and
      temporally interfering electric fields. It is possible, and even likely, that
      noninvasive brain stimulation may become the dominant form of brain treatments
      over the next 20 years. The future of brain stimulation therapeutics is bright.

PMID- 30098663
TI  - Neuromodulation.

PMID- 30098664
TI  - Health-Related Quality of Life in People Living with Psychotic Illness and
      Factors Associated with Its Variation.
AB  - OBJECTIVES: To establish whether the four-dimensional Assessment of Quality of
      Life (AQoL-4D) produces robust utility values in adults with psychotic illness,
      and identify health inequalities compared with the general population. METHODS:
      The AQoL-4D was completed by 1613 individuals with an International
      Classification of Diseases, Tenth Revision, psychotic illness in the 2010
      Australian National Survey of Psychosis. Utilities were assessed for this sample
      and 20 subgroups, and were compared with general population norms. Modified Cohen
      d was used as an index of effect size. Utilities were collapsed into 10 health
      related quality-of-life (HRQOL) bands or decades. RESULTS: HRQOL in people with
      psychotic illness was half of the maximum achievable utility (half-"full health")
      with a mean utility of 0.49 (95% confidence interval [CI] 0.48-0.51), and showing
      substantial variability across subgroups. Participants with essentially normal
      functioning had the highest mean utility (0.72; 95% CI 0.68-0.77), and those with
      very poor perceived mental health had the lowest (0.22; 95% CI 0.18-0.26). These
      subgroups showed the most variability. Negative symptoms also gave rise to
      substantial variation. Among diagnostic categories, only depressive psychosis had
      a large effect relative to delusional disorders. The distribution of utilities in
      people with psychotic illness differed markedly from that in the general
      population, with 6.8% versus 47.2% having values in the highest decade (>0.90
      1.00). Utilities were lower in every age group in people with psychosis.
      CONCLUSIONS: Profound HRQOL impacts are revealed by the AQoL-4D in people with
      psychotic illness, and marked variations in utilities were observed for key
      subjective and objective measures. We provide a suite of utility values for
      economic modeling studies and recommend the AQoL-4D for assessing HRQOL in people
      with psychotic illness.

PMID- 30098665
TI  - Generating EQ-5D-3L Utility Scores from the Dermatology Life Quality Index: A
      Mapping Study in Patients with Psoriasis.
AB  - OBJECTIVES: To develop an algorithm to predict the three-level EuroQol five
      dimensional questionnaire (EQ-5D-3L) utility scores from the Dermatology Life
      Quality Index (DLQI) in psoriasis. METHODS: This mapping study used data from the
      British Association of Dermatologists Biologic Interventions Register-a
      pharmacovigilance register comprising patients with moderate to severe psoriasis
      on systemic therapies. Conceptual overlap between the EQ-5D-3L and DLQI was
      assessed using Spearman rank correlation coefficients and exploratory factor
      analysis. Six regression methods to predict the EQ-5D-3L index (direct mapping)
      and two regression methods to predict EQ-5D-3L domain responses (response
      mapping) were tested. Random effects models were explored to account for repeated
      observations from the same individual. Estimated and actual EQ-5D-3L utility
      scores were compared using 10-fold cross-validation (in-sample) to evaluate
      predictive performance. Final models were selected using root mean squared error,
      mean absolute error, and mean error. RESULTS: The data set comprised 22,085
      observations for which DLQI and EQ-5D-3L were recorded on the same day. A
      moderate correlation was found between the measures (r = -0.47). Exploratory
      factor analysis showed that two EQ-5D-3L domains (pain/discomfort and
      depression/anxiety) were associated with all six DLQI domains. The best
      performing model used ordinary least squares with DLQI items, age, and sex as
      explanatory variables (with squared, cubic, and interaction terms). A tool was
      produced to allow users to map their data to the EQ-5D-3L, and includes
      algorithms that require fewer variables (e.g., total DLQI scores). CONCLUSIONS:
      This study produced mapping algorithms that can generate EQ-5D-3L utility scores
      from DLQI data for economic evaluations of health interventions for patients with
      psoriasis.

PMID- 30098666
TI  - Surveying the Cost-Effectiveness of the 20 Procedures with the Largest Public
      Health Services Waiting Lists in Ireland: Implications for Ireland's Cost
      Effectiveness Threshold.
AB  - OBJECTIVES: To survey the cost effectiveness of procedures with the largest
      waiting lists in the Irish public health system to inform a reconsideration of
      Ireland's current cost-effectiveness threshold of ?45,000/quality-adjusted life
      year (QALY). METHODS: Waiting list data for inpatient and day case procedures in
      the Irish public health system were obtained from the National Treatment Purchase
      Fund. The 20 interventions with the largest number of individuals waiting for
      inpatient and day case care were identified. The academic literature was searched
      to obtain cost-effectiveness estimates from Ireland and other high-income
      countries. Cost-effectiveness estimates from foreign studies were adjusted for
      differences in currency, purchasing power parity, and inflation. RESULTS: Of the
      top 20 waiting list procedures, 17 had incremental cost-effectiveness ratios
      (ICERs) lower than ?45,000/QALY, 14 fell below ?20,000/QALY, and 10 fell below
      ?10,000/QALY. Only one procedure had an ICER higher than the current threshold.
      Two procedures had ICERs reported for different patient and indication groups
      that lay on either side of the threshold. CONCLUSIONS: Some cost-effective
      interventions that have large waiting lists may indicate resource misallocation
      and the threshold may be too high. An evidence-informed revision of the threshold
      may require a reduction to ensure it is consistent with its theoretical basis in
      the opportunity cost of other interventions foregone. A limitation of this study
      was the difficulty in matching specific procedures from waiting lists with ICER
      estimates from the literature. Nevertheless, our study represents a useful
      demonstration of a novel concept of using waiting list data to inform cost
      effectiveness thresholds.

PMID- 30098667
TI  - Productivity Benefits of Medical Care: Evidence from US-Based Randomized Clinical
      Trials.
AB  - BACKGROUND: One of the key recommendations of the Second Panel on Cost
      Effectiveness in Health and Medicine is to take a societal perspective when
      evaluating new technologies-including measuring the productivity benefits of new
      treatments. Yet relatively little is known about the impact that new treatments
      have on labor productivity. OBJECTIVES: To examine the relationship between new
      drug treatments and gains in labor productivity across conditions in the United
      States and to evaluate which randomized clinical trials (RCTs) collected labor
      productivity data. METHODS: We collected data on US-based RCTs with work-ability
      surveys from searches of Google Scholar, PubMed, Scopus, the Cochrane Central
      Registry of Clinical Trials, and ClinicalTrails.gov. Combining RCT data with
      survey data from the Medical Expenditure Panel Survey, we assessed productivity
      changes from new drug treatments. RESULTS: During the last decade, some disease
      conditions have seen treatments that improve ability to work by as much as 60%.
      The annual increase in productivity gains attributable to new drug treatments was
      modest 1.1% (P = 0.53). Of the 5092 RCTs reviewed, ability-to-work measures were
      collected in 2% of trials. Work productivity surveys were more likely among
      prevalent medical conditions that affected individuals who worked, earned higher
      wages, and experienced larger reductions in hours worked as a consequence of
      disease diagnosis. CONCLUSIONS: From our data, we estimated that drug innovation
      increased productivity by 4.8 million work days per year and $221 billion in
      wages per year. These labor-sector benefits should be taken into account when
      assessing the socially optimal cost for new drug innovation.

PMID- 30098668
TI  - Cost-Effectiveness of Current and Emerging Treatments of Varicose Veins.
AB  - OBJECTIVES: To analyze the cost-effectiveness of current technologies
      (conservative care [CONS], high-ligation surgery [HL/S], ultrasound-guided foam
      sclerotherapy [UGFS], endovenous laser ablation [EVLA], and radiofrequency
      ablation [RFA]) and emerging technologies (mechanochemical ablation [MOCA] and
      cyanoacrylate glue occlusion [CAE]) for treatment of varicose veins over 5 years.
      METHODS: A Markov decision model was constructed. Effectiveness was measured by
      re-intervention on the truncal vein, re-treatment of residual varicosities, and
      quality-adjusted life-years (QALYs) over 5 years. Model inputs were estimated
      from systematic review, the UK National Health Service unit costs, and
      manufacturers' list prices. Univariate and probabilistic sensitivity analyses
      were undertaken. RESULTS: CONS has the lowest overall cost and quality of life
      per person over 5 years; HL/S, EVLA, RFA, and MOCA have on average similar costs
      and effectiveness; and CAE has the highest overall cost but is no more effective
      than other therapies. The incremental cost per QALY of RFA versus CONS was
      L5,148/QALY. Time to return to work or normal activities was significantly longer
      after HL/S than after other procedures. CONCLUSIONS: At a threshold of
      L20,000/QALY, RFA was the treatment with highest median rank for net benefit,
      with MOCA second, EVLA third, HL/S fourth, CAE fifth, and CONS and UGFS sixth.
      Further evidence on effectiveness and health-related quality of life for MOCA and
      CAE is needed. At current prices, CAE is not a cost-effective option because it
      is costlier but has not been shown to be more effective than other options.

PMID- 30098669
TI  - Effect of Interferon-Free Regimens on Disparities in Hepatitis C Treatment of US
      Veterans.
AB  - OBJECTIVES: To determine whether implementation of interferon-free treatment for
      hepatitis C virus (HCV) reached groups less likely to benefit from earlier
      therapies, including patients with genotype 1 virus or contraindications to
      interferon treatment, and groups that faced treatment disparities: African
      Americans, patients with HIV co-infection, and those with drug use disorder.
      METHODS: Electronic medical records of the US Veterans Health Administration
      (VHA) were used to characterize patients with chronic HCV infection and the
      treatments they received. Initiation of treatment in 206,544 patients with
      chronic HCV characterized by viral genotype, demographic characteristics, and
      comorbid medical and mental illness was studied using a competing events Cox
      regression over 6 years. RESULTS: With the advent of interferon-free regimens,
      the proportion treated increased from 2.4% in 2010 to 18.1% in 2015, an absolute
      increase of 15.7%. Patients with genotype 1 virus, poor response to previous
      treatment, and liver disease had the greatest increase. Large absolute increases
      in the proportion treated were observed in patients with HIV co-infection
      (18.6%), alcohol use disorder (11.9%), and drug use disorder (12.6%) and in
      African American (13.7%) and Hispanic (13.5%) patients, groups that were less
      likely to receive interferon-containing treatment. The VHA spent $962 million on
      interferon-free treatments in 2015, 1.5% of its operating budget. CONCLUSIONS:
      The proportion of patients with HCV treated in VHA increased sevenfold. The VHA
      was successful in implementing interferon treatment in previously undertreated
      populations, and this may become the community standard of care.

PMID- 30098671
TI  - Comparing the ICERs in Medicine Reimbursement Submissions to NICE and PBAC-Does
      the Presence of an Explicit Threshold Affect the ICER Proposed?
AB  - OBJECTIVES: The English National Institute for Health and Care Excellence (NICE)
      and the Australian Pharmaceutical Benefits Advisory Committee (PBAC) require
      evidence that a new medicine represents value for money before being publicly
      funded. NICE has an explicit threshold for cost effectiveness, whereas PBAC does
      not. We compared the initial incremental cost-effectiveness ratios (ICERs)
      presented by manufacturers in matched submissions to each decision-making body,
      with the aim of exploring the impact of an explicit threshold on these ICERs.
      METHODS: Data were extracted from matched submissions from 2005 to 2015. The
      ICERs in these submissions were compared within each pair and with respect to a
      cost-effectiveness threshold. RESULTS: Fifty-eight pairs of matched submissions
      were identified. The median difference between the ICERs ($2635/quality-adjusted
      life year [QALY]) was significantly greater than zero (Wilcoxon signed-rank test,
      P = 0.0299), indicating that the proposed ICERs in the submissions to NICE were
      higher than those in the matched submissions to PBAC. On 93% of occasions, NICE
      ICERs were within -$17,772 to +$48,422 of the corresponding PBAC ones (Bland
      Altman analysis), demonstrating poor agreement. When an implicit threshold of
      AUD$50,000/QALY was assumed for PBAC decision making, only eight pairs of
      submissions had discordant ICERs falling above or below the respective threshold.
      CONCLUSIONS: The significantly higher ICERs in the submissions to NICE than those
      to PBAC may be a consequence of NICE's explicit willingness-to-pay threshold,
      and/or other health system factors. Industry may be assuming an implicit
      threshold for PBAC when constructing their ICERs despite the lack of
      acknowledgement of such a threshold.

PMID- 30098672
TI  - Estimating Future Health Technology Diffusion Using Expert Beliefs Calibrated to
      an Established Diffusion Model.
AB  - OBJECTIVES: Estimates of future health technology diffusion, or future uptake
      over time, are a requirement for different analyses performed within health
      technology assessments. Methods for obtaining such estimates include constant
      uptake estimates based on expert opinion or analogous technologies and on
      extrapolation from initial data points using parametric curves-but remain
      divorced from established diffusion theory and modeling. We propose an approach
      to obtaining diffusion estimates using experts' beliefs calibrated to an
      established diffusion model to address this methodologic gap. METHODS: We
      performed an elicitation of experts' beliefs on future diffusion of a new preterm
      birth screening illustrative case study technology. The elicited quantities were
      chosen such that they could be calibrated to yield the parameters of the Bass
      model of new product growth, which was chosen based on a review of the diffusion
      literature. RESULTS: With the elicitation of only three quantities per diffusion
      curve, our approach enabled us to quantify uncertainty about diffusion of the new
      technology in different scenarios. Pooled results showed that the attainable
      number of adoptions was predicted to be relatively low compared with what was
      thought possible. Further research evidence improved the attainable number of
      adoptions only slightly but resulted in greater speed of diffusion. CONCLUSIONS:
      The proposed approach of eliciting experts' beliefs about diffusion and informing
      the Bass model has the potential to fill the methodologic gap evident in value of
      implementation and research, as well as budget impact and some cost-effectiveness
      analyses.

PMID- 30098670
TI  - Oncologists' Views on Using Value to Guide Cancer Treatment Decisions.
AB  - OBJECTIVES: Cancer costs have increased substantially in the past decades,
      prompting specialty societies to urge oncologists to consider value in clinical
      decision making. Despite oncologists' crucial role in guiding cancer care,
      current literature is sparse with respect to the oncologists' views on value.
      Here, we evaluated oncologists perceptions of the use and measurement of value in
      cancer care. METHODS: We conducted in-depth, open-ended interviews with 31 US
      oncologists practicing nationwide in various environments. Oncologists discussed
      the definition, measurement, and implementation of value. Transcripts were
      analyzed using matrix and thematic analysis. RESULTS: Oncologists' definitions of
      value varied greatly. Some described versions of the standard health economic
      definition of value, that is, cost relative to health outcomes. Many others did
      not include cost in their definition of value. Oncologists considered patient
      goals and quality of life as important components of value that they perceived
      were missing from current value measurement. Oncologists prioritized a patient
      centric view of value over societal or other perspectives. Oncologists were
      inclined to consider the value of a treatment only if they perceived treatment
      would pose a financial burden to patients. Oncologists had differing opinions
      regarding who should be responsible for determining whether care is low value but
      generally felt this should remain within the purview of the oncology community.
      CONCLUSIONS: Oncologists agreed that cost was an important issue, but disagreed
      about whether cost was involved in value as well as the role of value in guiding
      treatment. Better clarity and alignment on the definition of and appropriate way
      to measure value is critical to the success of efforts to improve value in cancer
      care.

PMID- 30098673
TI  - Sharing and the Provision of "Cost-Ineffective" Life-Extending Services to Less
      Severely Ill Patients.
AB  - BACKGROUND: Cost-utility analysis prioritizes services using cost, life-years,
      and the health state utility of the life-years. Nevertheless, a significant body
      of evidence suggests that the public would prefer more variables to be considered
      in decision making and at least some sharing of the budget with services for
      severe conditions that are not cost-effective because of their high cost.
      OBJECTIVES: To examine whether this preference for sharing persists for less
      severe conditions when both cost effectiveness and illness severity would
      indicate that resources should be allocated to other services. METHODS: Survey
      respondents were asked to divide a budget between two patients facing life
      threatening illnesses. The severity of the illnesses differed and the price of
      treatment was varied. RESULTS: Sharing occurred in all scenarios including
      scenarios in which the illness was less severe and services were not cost
      effective. Results are consistent with behavior commonly observed in other
      contexts. CONCLUSIONS: Results suggest that sharing per se is important and that
      the public would support some funding of cost-ineffective services for less
      severe health problems.

PMID- 30098674
TI  - Test-Retest Reliability of Discrete Choice Experiment for Valuations of QLU-C10D
      Health States.
AB  - BACKGROUND: Recently, a newly developed cancer-specific multiattribute utility
      instrument based on the widely used health-related quality of life instrument,
      the European Organisation for Research and Treatment of Cancer QLQ-C30, was
      introduced: the QLU-C10D. For the elicitation of utility weights, a discrete
      choice experiment (DCE) was designed. Our aim was to investigate the DCE in terms
      of individual choice consistency and utility estimate consistency by applying a
      test-retest design. METHODS: We conducted the study in general population samples
      in Germany and France. The DCE was administered via a web-based self-complete
      survey using online panels. Respondents were presented 16 choice sets comprising
      11 attributes with 4 levels each. Retest was conducted 4 to 6 weeks after first
      assessment. We used kappa and percentage agreement as measures of choice
      consistency and both intraclass correlations and mean utility differences as
      measures of utility estimate consistency. RESULTS: A total of 300 German
      respondents (31% female, mean age 48 years [SD 14]) and 305 French respondents
      (46% female, mean age 47 years [SD 16]) completed test and retest assessments.
      Individual choice consistency was moderate to high (Germany: kappa = 0.605,
      percentage agreement = 80.2%; France: kappa = 0.411, percentage agreement =
      70.6%). Utility estimate consistency was high when considering intraclass
      correlations (all >0.79). Mean utility differences were 0.08 in the German sample
      and 0.05 in the French sample. CONCLUSIONS: Results indicate that the designed
      DCE elicits stable health state preferences rather than guesses or mood-specific
      or condition-specific judgments. Nevertheless, the identified mean utility
      differences between test and retest need to be taken into account when
      determining minimal important differences for the QLU-C10D in future research.

PMID- 30098675
TI  - Patient-Reported Outcome Measures in the Food and Drug Administration Pilot
      Compendium: Meeting Today's Standards for Patient Engagement in Development?
AB  - BACKGROUND: In 2016, the Food and Drug Administration (FDA) released a Pilot
      Clinical Outcome Assessment Compendium (COA Compendium) intended to foster
      patient-focused drug development (PFDD). However, it is unclear whether patient
      perspectives were solicited during development or validation of the included
      patient-reported outcome (PRO) measures. OBJECTIVE: To examine the pedigree of a
      sample of measures included in the COA Compendium. METHODS: PROs included in
      chapters 1 or 2 of the COA Compendium were extracted and three reviewers
      independently searched PubMed and Google to identify information on measure
      pedigree. Data on method and stage of measure development where patient
      engagement took place were documented. RESULTS: Among the 26 evaluated PRO
      measures, we were unable to identify information on development or validation on
      nearly half the sample (n = 12). Among the remaining 14 measures, 5 did not
      include any evidence of patient engagement; 2 engaged patients during concept
      elicitation only; 1 engaged patients during psychometric validation only; and 6
      engaged patients during both concept elicitation and cognitive interviewing.
      Measures either previously qualified or submitted for qualification were more
      likely to include patient engagement. CONCLUSIONS: For the FDA Pilot COA
      Compendium to fulfill its purpose of fostering PFDD, it needs fine-tuning to
      reflect today's standards, improving transparency and facilitating clear
      identification of included measures so that the level of patient engagement,
      among other factors, can be properly assessed. Suggested improvements include
      identifying clinical trials that correspond to the COA Compendium's use in drug
      development; more clearly identifying which measure is referred to; and including
      only those measures that already qualified or undergoing qualification.

PMID- 30098676
TI  - Qualitative Research to Explore the Patient Experience of X-Linked
      Hypophosphatemia and Evaluate the Suitability of the BPI-SF and WOMAC(r) as
      Clinical Trial End Points.
AB  - BACKGROUND: X-linked hypophosphatemia (XLH) is a rare genetic disorder
      characterized by renal phosphate wasting and defective bone mineralization.
      Symptoms include bone pain, joint pain, stiffness, and fatigue. Published
      evidence regarding the patient experience of XLH is sparse and no XLH-specific
      outcome measures have been validated. OBJECTIVES: To understand the symptoms,
      impacts, and patient experience of XLH and to evaluate the face and content
      validity of the Western Ontario and McMaster Universities Osteoarthritis Index
      (WOMAC(r)) and the Brief Pain Inventory Short Form (BPI-SF) for use as end points
      in XLH clinical trials. METHODS: Face-to-face, qualitative, semistructured
      interviews were conducted with 18 adults with XLH in the United States using
      concept elicitation and cognitive debriefing techniques. Open-ended questioning
      elicited spontaneous concepts focusing on XLH-associated symptoms and functional
      limitations. Cognitive debriefing of the WOMAC(r) and BPI-SF assessed the
      relevance and patient understanding of item wording, recall period, and response
      options. RESULTS: Various distinct symptom concepts were elicited including pain
      symptoms, dental symptoms, sensory symptoms, tiredness/fatigue symptoms, and
      musculoskeletal symptoms. Participants reported experiencing significant bone and
      joint pain, stiffness, mobility limitations, and an impact on their ability to
      work. Cognitive interviewing found both instruments to be relevant and well
      understood by most patients. CONCLUSIONS: The interviews generated rich,
      qualitative insights into the patient experience of XLH. Cognitive debriefing of
      the BPI-SF and WOMAC(r) supported their value as XLH clinical trial end points.
      Future research will assess the psychometric properties of these instruments for
      use in the XLH population.

PMID- 30098678
TI  - Advocating a Paradigm Shift in Health-State Valuations: The Estimation of Time
      Preference Corrected QALY Tariffs.
AB  - BACKGROUND: Despite evidence of nonproportional trade-offs in time trade-off
      exercises and the explicit incorporation of exponential discounting in health
      technology assessment calculations, quality-adjusted life-year (QALY) tariffs are
      currently still established under the assumption of linear time preferences.
      OBJECTIVES: The aim of this study was to introduce a general method of
      accommodating for nonlinear time preferences in discrete choice experiment (DCE)
      duration studies and to evaluate its impact on estimated QALY tariffs. METHODS: A
      parsimonious utility function is proposed that accommodates any discounting
      function and preserves linear time preferences as a special case. Based on an
      efficient DCE design and 1775 respondents from a nationally representative
      scientific household panel, preferences and QALY tariffs for the Dutch SF-6D were
      estimated while accommodating for nonlinear time preferences via exponential and
      hyperbolic discounting functions. RESULTS: When the discount rate was estimated
      directly, we found strong evidence of nonlinear time preferences (with an
      exponential and hyperbolic discount rate of 5.7% and 16.5%, respectively). When
      the discount rate was estimated as a function of health state severity, we found
      that years lived in better health states are discounted minus years lived in
      impaired health states. Finally, the best statistical fit was obtained when using
      a hyperbolic discount function, which resulted in smaller QALY decrements and
      fewer health states classified as worse than immediate death. CONCLUSIONS: Our
      results highlight the relevance and even necessity of a paradigm shift in health
      valuation studies in favor of time-preference corrected QALY tariffs, with
      potentially important implications for health technology assessment calculations
      and regulatory decisions.

PMID- 30098679
TI  - Cervicovaginal microbiota, women's health, and reproductive outcomes.
AB  - The human microbiome project has shown a remarkable diversity of microbial
      ecology within the human body. The vaginal microbiota is unique in that in many
      women it is most often dominated by Lactobacillus species. However, in some women
      it lacks Lactobacillus spp. and is comprised of a wide array of strict and
      facultative anaerobes, a state that broadly correlates with increased risk for
      infection, disease, and poor reproductive and obstetric outcomes. Interestingly,
      the level of protection against infection can also vary by species and strains of
      Lactobacillus, and some species although dominant are not always optimal. This
      factors into the risk of contracting sexually transmitted infections and possibly
      influences the occurrence of resultant adverse reproductive outcomes such as
      tubal factor infertility. The composition and function of the vaginal microbiota
      appear to play an important role in pregnancy and fertility treatment outcomes
      and future research in this field will shed further translational mechanistic
      understanding onto the interplay of the vaginal microbiota with women's health
      and reproduction.

PMID- 30098677
TI  - Initial Development and Content Validation of a Health-Related Symptom Index for
      Persons either Treated or Monitored for Anal High-Grade Squamous Intraepithelial
      Lesions.
AB  - BACKGROUND: Anal cancer, caused by oncogenic types of human papillomavirus, is a
      growing problem in the United States. A key focus of anal cancer prevention has
      been screening for and treating precancerous high-grade squamous intraepithelial
      anal lesions (HSILs). OBJECTIVES: To develop a health-related symptom index for
      HSIL using qualitative techniques because anal HSIL and its treatment may have a
      negative impact on health-related quality of life (HRQOL), and no HRQOL measure
      specific to this condition and treatment currently exists. METHODS: Expert
      consultation was used to guide one-on-one concept elicitation interviews with
      participants to identify HRQOL aspects they attribute to their anal HSIL and its
      treatment. This resulted in a draft instrument, which was administered to an
      independent participant sample, where cognitive interview techniques assessed
      comprehension. RESULTS: Eighteen anal HSIL-related concepts were identified by
      the expert panel. Across the 41 concept elicitation interviews, 23 items
      representing physical symptoms, physical impacts, and psychological symptoms were
      identified to comprise the initial measure, which was then evaluated during three
      rounds of cognitive interviews (n = 45). Several questionnaire aspects were
      refined on the basis of participant input, with three additional items added per
      expert/participant recommendation. One item was removed because of poor
      comprehension, resulting in a 25-item measure. CONCLUSIONS: Using state-of-the
      art qualitative methodology, we have established the content validity of this new
      instrument, the ANCHOR Anal HSIL Health-Related Symptom Index. Quantitative
      validation efforts are currently underway. The participant-driven process of
      developing this tool will facilitate a participant-centered evaluation of the
      impact on morbidity for treatment of anal HSIL or observation without treatment.

PMID- 30098680
TI  - Relevance of assessing the uterine microbiota in infertility.
AB  - Technical advances in massive parallel sequencing have allowed the
      characterization of the whole reproductive tract microbiome in all the
      compartments beyond the vagina. The microbiota in the uterine cavity seem to be a
      continuum from the microbiota in the vagina, but several works have reported
      significant differences between vaginal and endometrial microbiota, highlighting
      the relevance of assessing the upper genital tract microbiota to better
      understand the potential roles of bacteria in the physiological and pathological
      processes taking place in the uterine cavity, including embryo implantation,
      pregnancy maintenance, and other gynecological diseases. However, the study of
      the endometrial microbiota, as with other low-biomass microbiota, presents
      important hurdles because, due to the small amount of starting material, they are
      easily contaminated by exogenous bacterial DNA. For this reason, careful and
      appropriate investigation of the endometrial microbiota is of outstanding
      importance to detect uterine dysbiosis that may impact the reproductive function.

PMID- 30098681
TI  - Is preimplantation genetic testing for aneuploidy an essential tool for embryo
      selection or a costly 'add-on' of no clinical benefit?

PMID- 30098682
TI  - The pros and cons of preimplantation genetic testing for aneuploidy: clinical and
      laboratory perspectives.

PMID- 30098683
TI  - Clinically integrated health care: optimizing our approach to reproductive
      medicine.

PMID- 30098684
TI  - Fertility preservation and reproduction in patients facing gonadotoxic therapies:
      an Ethics Committee opinion.
AB  - Chemotherapy and radiation therapy often result in reduced fertility. Patients
      receiving gonadotoxic treatment should be informed of options for fertility
      preservation and future reproduction prior to such treatment. Reproduction in the
      context of cancer also raises a number of ethical issues related to the welfare
      of both patients and offspring. This document replaces the document titled,
      "Fertility preservation and reproduction in patients facing goandotoxic
      therapies," last published in 2013.

PMID- 30098686
TI  - Increasing evidence of the role of the sperm epigenome in embryogenesis:
      oligoasthenoteratozoospermia, altered embryo DNA methylation, and miscarriage.

PMID- 30098685
TI  - The role of immunotherapy in in vitro fertilization: a guideline.
AB  - Adjuvant immunotherapy treatments in in vitro fertilization (IVF) aim to improve
      the outcome of assisted reproductive technology (ART) in both the general ART
      population as well as subgroups such as patients with recurrent miscarriage or
      implantation failure. The purpose of this guideline is to evaluate the role of
      immunomodulating therapy in ART. Unfortunately, many of the evaluated therapies
      lack robust evidence from well-designed adequately powered randomized controlled
      trials to support their use. Immunotherapies reviewed in the present document are
      either not associated with improved live-birth outcome in IVF or have been
      insufficiently studied to make definitive recommendations.

PMID- 30098687
TI  - Are infertile patients at greater risk of cesarean delivery?

PMID- 30098688
TI  - Endometriosis and pregnancy outcome.

PMID- 30098689
TI  - Current status and future prospects of noninvasive preimplantation genetic
      testing for aneuploidy.

PMID- 30098690
TI  - Unleashing the potential of stem cells to help poor responders.

PMID- 30098691
TI  - Speak up! Equipping women with polycystic ovary syndrome to have high quality
      encounters with their providers.

PMID- 30098692
TI  - Can any meta-analysis help us manage polycystic ovary syndrome?

PMID- 30098693
TI  - Optimal management of symptomatic cesarean scar defects.

PMID- 30098695
TI  - Celiac disease is not more prevalent in patients undergoing in vitro
      fertilization and does not affect reproductive outcomes with or without
      treatment: a large prospective cohort study.
AB  - OBJECTIVE: To study the prevalence of celiac disease in the infertile population
      undergoing in vitro fertilization (IVF) and assess outcomes. DESIGN: Prospective
      cohort study. SETTING: A single infertility center from January 2016 to March
      2017. PATIENT(S): Women 18-45 years of age participating in IVF. INTERVENTION(S):
      Patients had serum tissue transglutaminase (tTG) and endomysial (EMA) IgA testing
      to screen for celiac disease and completed a 10-question "yes or no" survey to
      assess their medical history, previous testing, dietary habits, and pertinent
      symptoms. MAIN OUTCOME MEASURE(S): IVF cycle outcomes were compared between
      seronegative and seropositive patients. RESULT(S): Of 1,000 patients enrolled,
      995 completed serologic screening and 968 underwent oocyte retrieval. Eighteen
      patients screened positive for both tTG and EMA (1.8%) and 10 additional patients
      (1.0%) screened positive for one of the two antibodies. The number of mature
      oocytes retrieved, fertilization rates, and blastulation rates were equivalent
      between seronegative and seropositive patients. There were 987 patients who
      completed the questionnaire (98.7%), and 84 reported being gluten free (8.5%).
      Those who reported being gluten free were no more likely to be antibody positive
      than the general population. Furthermore, a low-gluten diet was not associated
      with markers of ovarian reserve, oocytes retrieved, fertilization, blastulation,
      sustained implantation and pregnancy loss rates. CONCLUSION(S): The prevalence of
      seropositive celiac disease was consistent with that of the general population
      (2.8%). Patients who were seropositive for celiac disease-related antibodies had
      outcomes equivalent to seronegative patients, and patients with a gluten-free
      diet did not have improved outcomes.

PMID- 30098694
TI  - Factors associated with increased odds of cesarean delivery in ART pregnancies.
AB  - OBJECTIVE: To quantify the effect of medical and obstetrical factors on the odds
      of cesarean delivery, comparing assisted reproductive technology (ART)-treated
      women and women with subfertility not treated with ART versus fertile women.
      DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Singleton
      deliveries to primiparous women; with the source of this data being the
      Massachusetts vital and hospital records linked to the Society for Assisted
      Reproductive Technology Clinic Outcome Reporting System data (2004-2010).
      INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mode of delivery. RESULT(S): The
      173,130 deliveries included 5,768 ART-treated, 2,657 subfertile (1,627 non-ART
      medically assisted reproduction [MAR] and 1,030 unassisted infertile), and
      164,705 fertile pregnancies and 117,743 vaginal and 55,387 cesarean deliveries.
      ART-treated women were older, more often white and non-Hispanic, and with more
      private insurance, previous uterine surgery, gestational diabetes, pregnancy
      hypertension, bleeding, and placental complications than fertile women. Overall
      rates of cesarean delivery were 45.7%, 43.3%, and 31.1% for ART-treated,
      subfertile, and fertile women and 41.7% and 45.9% for MAR and unassisted
      infertile deliveries. When adjusted for demographics, underlying medical factors,
      previous uterine surgery, and placental and delivery complications, adjusted odds
      ratios (ORs) compared with fertile women were 1.27 for ART-treated and 1.15 for
      subfertile women, with greater odds among unassisted infertile (OR 1.26) but not
      MAR (OR 1.09) women. The strongest confounders of odds of cesarean delivery were
      age and previous uterine surgery. CONCLUSION(S): ART and unassisted infertility
      were associated with greater odds of cesarean compared with fertile women.
      Underlying medical and obstetrical risks had strong confounding effects strongly
      attenuating the odds for cesarean delivery.

PMID- 30098696
TI  - Ninety babies born after round spermatid injection into oocytes: survey of their
      development from fertilization to 2 years of age.
AB  - OBJECTIVE: To compare physical and cognitive development of babies born after
      round spermatid injection (ROSI) with those born after natural conception.
      DESIGN: Comparison of efficiencies of ROSI and ICSI using testicular spermatozoa,
      performed in the St. Mother Clinic. Physical and cognitive development of ROSI
      babies recorded by parents in the government-issued Mother-Child Handbook was
      checked and verified by attending pediatricians. Data included baby's weight gain
      and response to parents' voice/gesture. SETTING: Assisted reproduction technology
      practice. PATIENT(S): A total of 721 men participated in ROSI; 90 ROSI babies
      were followed for 2 years for their physical and cognitive development. Control
      subjects were 1,818 naturally born babies. INTERVENTION(S): Surgical retrieval of
      spermatogenic cells from testes; selection and injection of round spermatids into
      oocytes; oocyte activation, in vitro culture of fertilized eggs, and embryo
      transfer to mothers. MAIN OUTCOME MEASURE(S): Physical and cognitive development
      of ROSI babies (e.g., body weight increase, response to parents, and
      understanding and speaking simple language) compared with naturally born babies.
      RESULT(S): Of 90 ROSI babies, three had congenital aberrations at birth, which
      corrected spontaneously (ventricular septa) or after surgery (cleft lip and
      omphalocele). Physical and cognitive development of ROSI babies was similar to
      those of naturally born babies. CONCLUSION(S): There were no significant
      differences between ROSI and naturally conceived babies in either physical or
      cognitive development during the first 2 years after birth. CLINICAL TRIAL
      REGISTRATION NUMBER: UMIN Clinical Trials Registry UMIN000006117.

PMID- 30098697
TI  - Maternal antithyroid antibodies and euploid miscarriage in women with recurrent
      early pregnancy loss.
AB  - OBJECTIVE: To determine whether an association exists between maternal
      antithyroid antibodies and euploid miscarriage in women with recurrent early
      pregnancy loss (REPL). DESIGN: Observational cohort study. SETTING: Two academic
      medical centers. PATIENT(S): Women seen between 2004-2015 with a history of REPL,
      who were euthyroid or had subclinical hypothyroidism, had maternal antithyroid
      antibody testing and had at least one subsequent early pregnancy loss (<10 weeks'
      gestation). INTERVENTION(S): Thyroid function and antibodies were measured at
      consultation. Subsequent miscarriages were assessed by conventional cytogenetic
      analysis, and when indicated, microsatellite analysis and/or comparative genomic
      hybridization/single nucleotide polymorphisms were performed. MAIN OUTCOME
      MEASURE(S): Determine whether maternal antithyroid antibodies are associated with
      euploid miscarriage. RESULT(S): Cohort consisted of 74 subjects with REPL who had
      130 subsequent early pregnancy losses. The prevalence of maternal antithyroid
      antibodies in the cohort was 17.6%. Mean TSH was significantly higher among
      subjects with maternal antithyroid antibodies. Otherwise, no significant
      differences in demographics were noted. When comparing types of early pregnancy
      losses between the two groups, a trend toward having more miscarriages than
      nonvisualized pregnancy losses was noted among subjects with maternal antithyroid
      antibodies (70% and 30%) compared with subjects without maternal antithyroid
      antibodies (55% and 43%). No significant difference was noted in the frequency of
      euploid miscarriage between subjects with and without maternal antithyroid
      antibodies (42% vs. 56%). CONCLUSION(S): Our study did not demonstrate an
      association between euploid miscarriage and maternal antithyroid antibodies in
      subjects with a history of REPL. Therefore, testing or treatment in this cohort
      may not be warranted.

PMID- 30098698
TI  - Obstetric complications after laparoscopic excision of posterior deep
      infiltrating endometriosis: a case-control study.
AB  - OBJECTIVE: To study obstetric outcomes and complications in women with previously
      excised posterior deep infiltrating endometriosis (DIE) in comparison with women
      without endometriosis. DESIGN: Matched case-control study. SETTING: Tertiary
      level academic center. PATIENT(S): All surgeries for endometriosis performed in
      the Department of Gynecology and Gynecological Oncology, University of Bern
      between March 2004 and July 2015, were assessed. Inclusion criteria included
      complete laparoscopic excision of posterior DIE. Exclusion criteria included
      concomitant hysterectomies, refusal to participate, and patients lost to follow
      up. Each subsequent pregnancy was matched to three controls by maternal age,
      parity, history of cesarean, and mode of conception. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Obstetric complications. RESULT(S): Among 841 patients with
      surgically diagnosed endometriosis, 125 satisfied the inclusion and exclusion
      criteria. Of these, 73 pregnancies resulted, although a further 11 patients were
      excluded owing to early miscarriages or extrauterine pregnancies. The final study
      cohort included 62 singleton pregnancies matched to 186 controls. The analysis
      identified an increased risk of placenta previa, gestational hypertension, and
      intrauterine growth restriction for the case group. The possibility of successful
      vaginal delivery was similar between groups. Moreover, no significant increase in
      risk of maternal and neonatal delivery complications, except for a slightly
      higher postpartum blood loss in the case group, was observed. CONCLUSION(S):
      Despite previous surgical excision, women with history of DIE present a higher
      risk of placenta previa, gestational hypertonia, and intrauterine growth
      restriction during pregnancy. Previous surgery for DIE does not seem to
      predispose to failed vaginal delivery.

PMID- 30098699
TI  - Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic
      premature ovarian insufficiency.
AB  - OBJECTIVE: To analyze whether telomere length, X-chromosome inactivation (XCI),
      and androgen receptor (AR) GAG polymorphism are related to idiopathic premature
      ovarian insufficiency (POI). DESIGN: Case-control study. SETTING: University
      hospital. PATIENT(S): A total of 121 women, including 46 nonsyndromic POI and 75
      controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age, weight, height,
      body mass index (BMI), systolic and diastolic arterial pressure, E2,
      androstenedione, T, and C-reactive protein were assessed. Telomere length was
      estimated by quantitative real-time polymerase chain reaction, XCI was measured
      using the Human Androgen Receptor and X-linked retinitis pigmentosa 2 (RP2)
      methylation assays. AR and FMR1 polymorphism was assessed by quantitative
      fluorescent polymerase chain reaction and sequencing. RESULT(S): Premature
      ovarian insufficiency women had a higher mean age, weighed less, and exhibited
      lower C-reactive protein, E2, and androstenedione levels. The AR polymorphism did
      not differ between the groups. Four patients had premutation (55-200 CGG
      repeats), and none displayed a full mutation in the FMR1 gene. However, patients
      with POI showed shorter telomere length and higher frequency of skewed XCI.
      Extreme skewing (>=90%) was observed in 15% of women with POI, and shorter
      telomeres correlated with XCI skewing in both groups. CONCLUSION(S): Skewed XCI
      and shortened telomere length were associated with idiopathic POI, despite no
      alterations in the AR and FMR1 genes. Additionally, there is a tendency for women
      with short telomeres to exhibit skewed XCI.

PMID- 30098700
TI  - Mutation profiles and clinical characteristics of Chinese males with isolated
      hypogonadotropic hypogonadism.
AB  - OBJECTIVE: To investigate the mutation profiles and clinical characteristics of
      Chinese males with isolated hypogonadotropic hypogonadism (IHH) and discover new
      pathogenic genes that cause IHH. DESIGN: A gene panel, including 31 known IHH
      genes and 52 candidate genes, was used to perform semiconductor next-generation
      sequencing. SETTING: University hospital. PATIENTS: One hundred thirty-eight
      sporadic male IHH patients and 10 IHH families; 100 healthy men with normal
      fertility served as control subjects. INTERVENTIONS(S): None. MAIN OUTCOME
      MEASURE(S): Targeted next-generation sequencing, polymerase chain reaction and
      sequencing, pedigree analysis, and bioinformatics analysis. RESULT(S): Variants
      were distributed uniformly throughout 52 genes (52/83, 62.65%), including 16
      (16/31, 51.61%) causal genes and 36 (36/52, 69.23%) candidate genes. Six new
      pathogenic variants and 52 likely pathogenic variants were identified in 16 genes
      known to cause nIHH/KS (normosmic IHH/Kallmann syndrome). In the 148 probands,
      PROKR2 (22/148, 14.86%), CHD7, FGFR1, and KAL1 had high mutation rates, and 8.78%
      (13/148) of the patients carried at least two variants in known genes. In
      addition, variants were identified in 36 candidate genes, and EGFR, ERBB4, PAX6,
      IGF1, SEMA4D, and SEMA7A should be prioritized for further research and genetic
      testing in IHH. CONCLUSION(S): The mutation frequency of IHH-causal genes in
      Chinese HAN males was different from the data reported in white populations.
      Oligogenic inheritance was a common phenomenon in IHH. Our study expands the
      mutation profile for IHH, and the new likely pathogenic genes identified in our
      study warrant further research in GnRH neuronal networks.

PMID- 30098701
TI  - Identification of biparental and diploid blastocysts from monopronuclear zygotes
      with the use of a single-nucleotide polymorphism array.
AB  - OBJECTIVE: To select normal fertilized diploid blastocysts in patients who had
      only monopronucleated (1PN) embryos for transfer. DESIGN: Experimental study.
      SETTING: University-affiliated center. PATIENT(S): Couples who were undergoing
      intracytoplasmic sperm injection treatment and had 1PN blastocysts.
      INTERVENTION(S): In a preliminary test, limited cells of parthenogenetic human
      embryonic stem cells (phESCs) and normal fertilized blastocysts were analyzed
      with the use of a low-density single-nucleotide polymorphism (SNP) array to
      identify the distribution pattern and rate of heterozygosity. In the clinical
      application, 1PN blastocysts were analyzed with the use of the SNP array. Only
      diagnosed normal blastocysts were transferred. The diagnosed uniparental
      blastocysts were validated by imprinted gene expression. MAIN OUTCOME MEASURE(S):
      Distribution pattern and rate of heterozygosity between parthenogenesis and
      normal fertilization. RESULT(S): In the pretest, phESCs exhibited distinct
      distribution pattern and lower rate of heterozygosity, compared with normal
      fertilized blastocysts after SNP analysis. In particular, homozygous hESCs showed
      a panhomozygosity distribution pattern, hybrid phESCs showed a partial
      homozygosity distribution pattern, and normal fertilized blastocysts exhibited a
      panheterozygosity distribution pattern with an average of 20.21% heterozygosity
      rate; 13.6% was found to be the minimum cutoff to predict normal fertilized
      samples. In the clinical application, 24 1PN blastocysts were analyzed; 10/24
      showed chromosomal abnormalities, 3/24 showed panhomozygosity with 0.45%-0.8%
      heterozygosity, and 1/24 showed partial homozygosity with 6.54% heterozygosity.
      The remaining 10 blastocysts, with a panheterozygosity distribution pattern and
      higher genomic heterozygosity rate, were diagnosed as normal-fertilization
      diploid embryos; three were transferred and resulted in two healthy newborns.
      CONCLUSION(S): The low-density SNP array might serve as a cost-effective method
      to identify biparental origin and diploid 1PN blastocysts for transfer.

PMID- 30098702
TI  - Hysteroscopic repair of cesarean scar isthmocele.
AB  - OBJECTIVE: To demonstrate an approach to the hysteroscopic repair of cesarean
      scar isthmocele and discuss its association with secondary infertility. DESIGN: A
      step-by-step explanation of the procedure with surgical video footage. SETTING:
      Academic medical center. PATIENT(S): Two patients undergoing hysteroscopic repair
      of symptomatic cesarean scar isthmoceles. Surgical candidates for this procedure
      include patients with a symptomatic isthmocele and a residual myometrial
      thickness of at least 3 mm confirmed with pre-operative imaging. INTERVENTION(S):
      Operative hysteroscopy is performed using a step-wise approach: identification of
      relevant anatomy; resection of the cephalad edge of fibrosis; resection of the
      caudad edge of fibrosis; and ablation of the isthmocele base. MAIN OUTCOME
      MEASURE(S): Restoration of the contour between the uterine cavity and cervical
      canal. RESULT(S): Hysteroscopic resection of cesarean scar isthmocele is
      successfully performed in both cases presented. Postoperatively, both patients
      had resolution of their symptoms. CONCLUSION(S): The surgical approach presented
      in this video can result in the successful revision of a cesarean scar
      isthmocele. Current literature supports a role for hysteroscopic isthmoplasty in
      treating isthmocele-related abnormal uterine bleeding. However, more evidence is
      required on the safety of conceiving following hysteroscopic isthmoplasty, and
      its use in the setting of secondary infertility.

PMID- 30098703
TI  - Retraction notice to Breast Cancer Risk, Dietary Intake, and
      Methylenetetrahydrofolate reductase (MTHFR) Single Nucleotide Polymorphisms Food
      and Chemical Toxicology 48/7 (2010) 1881 - 1885.

PMID- 30098704
TI  - The effect of dental pulp-capping materials on hard-tissue barrier formation: A
      systematic review and meta-analysis.
AB  - BACKGROUND: The authors of this systematic review aimed to compare the effects of
      pulp-capping materials on hard-tissue barrier formation using histologic
      assessments. TYPE OF STUDIES REVIEWED: The authors included randomized controlled
      trials and controlled clinical trials in humans, with vital therapies performed
      on healthy permanent teeth undergoing experimental mechanical pulp exposures.
      They searched electronically in the PubMed, Cochrane, Embase, and Summon
      databases and carried out a manual search. Twenty-seven full-text articles were
      eligible for inclusion in the systematic review. After data extraction, the
      authors performed 2 sets of meta-analyses with odds ratios (OR) and their 95%
      confidence intervals (CI) on 22 studies. Ten studies compared mineral trioxide
      aggregate (MTA) with calcium hydroxide (CH), and 12 compared bonding agents with
      CH. The authors assessed bias by means of Cochrane Collaboration's tool for
      assessing risk, funnel plots, and Harbord test. RESULTS: The use of MTA was
      associated with a higher rate of hard-tissue barrier formation than CH. The OR
      comparing the 2 groups was 2.45 (95% CI, 1.39 to 4.29; P = .002). Use of bonding
      agents was associated with a lower rate of hard-tissue barrier formation than CH.
      The OR comparing the 2 groups was 0.02 (95% CI, 0.01 to 0.05; P < .001).
      CONCLUSIONS AND PRACTICAL IMPLICATIONS: The results suggest that MTA and CH have
      positive effects on hard-tissue barrier formation. On the basis of the evidence,
      the authors conclude that MTA has better effects than CH regarding dental pulp
      protection in the capping of mechanical pulp exposures. Conversely, bonding
      agents are inferior to CH.

PMID- 30098705
TI  - Syphilis Maligna: A Presentation to Bear in Mind.
AB  - Malignant syphilis is an uncommon form of secondary syphilis associated with HIV
      infection. Clinically, it is characterized by necrotic nodules and generalized
      ulcerated lesions. We present 4 cases of malignant syphilis diagnosed after
      evaluating syphilis cases diagnosed at our hospital between 2012 and 2016. We
      describe the epidemiologic, clinical, histiopathologic, and serologic
      characteristics of malignant syphilis and explore its response to treatment and
      association with HIV infection. Although malignant syphilis is uncommon, there
      has been an increase in the number of cases published in recent years,
      particularly in young HIV-positive patients. Malignant syphilis must be
      contemplated in the differential diagnosis of HIV patients with ulcerated,
      necrotic lesions.

PMID- 30098706
TI  - The National Echocardiography Database Australia (NEDA): Rationale and
      methodology.
AB  - The National Echocardiography Database Australia (NEDA) is a new echocardiography
      database collecting digital measurements on both a retrospective and prospective
      basis. To date, echocardiographic data from 435,133 individuals (aged 61.6 +/-
      17.9 years) with linkage to 59,725 all-cause deaths during a median of 40 months
      follow-up have been collected. These data will inform a number of initial
      analyses focusing on pulmonary hypertension, aortic stenosis and the role of
      artificial intelligence to facilitate accurate diagnoses of cardiac
      abnormalities.

PMID- 30098707
TI  - Usefulness and Safety of Rivaroxaban in Patients Following Isolated Mitral Valve
      Replacement With a Mechanical Prosthesis.
AB  - Rivaroxaban has previously been tested in experimental and animal models with
      encouraging results. We prospectively selected seven patients between May 2017
      and January 2018 who underwent isolated mitral valve replacement with a
      mechanical prosthesis and had unstable INR control at least 3 months after
      surgery. An intervention of rivaroxaban 15mg was then administered twice daily
      for a period of 90days. No patient presented intracardiac thrombus, reversible
      ischemic neurological deficit, ischemic or hemorrhagic stroke, and
      hospitalization or death during 3 months of follow-up. Two patients eradicated
      the presence of spontaneous echo contrast. Mean and peak pressure gradients, peak
      velocity, effective orifice area, and PHT were similar before and after the
      intervention. In conclusion, the use of rivaroxaban for 90days in seven patients
      after replacement of mitral valve with the mechanical prosthesis did not present
      thromboembolic or bleeding events (NCT02894307).

PMID- 30098708
TI  - Meta-Analysis of the Prognostic Value of Psoas-Muscle Area on Mortality in
      Patients Undergoing Transcatheter Aortic Valve Implantation.
AB  - We performed a meta-analysis of currently available studies assessing prognostic
      value of psoas-muscle area (PMA) on mortality in patients who underwent
      transcatheter aortic valve implantation (TAVI). MEDLINE and EMBASE were searched
      through May 2018 to identify studies reporting >=1-year all-cause mortality in
      PMA-stratified TAVI patients. A hazard ratio of follow-up (including early)
      mortality for "lowest-quantile" versus "higher-quantiles" PMA. Study-specific
      estimates were combined in the random-effects model. Our search identified 6
      eligible studies enrolling a total of 1,237 TAVI patients with 1-year to 2-year
      (midterm) follow-up. A primary meta-analysis pooling all hazard ratios for
      "lowest-quantile versus higher-quantiles" PMA demonstrated significantly higher
      mortality in "lowest-quantile" than "higher-quantiles" patients (p <0.0001). A
      subgroup meta-analysis indicated no significant difference in mortality between
      "<50th- and >=50th-percentile" patients (p = 0.95), but significantly higher
      mortality in "lowest-tertile" than "higher-tertiles" patients (p = 0.0009) and in
      "lowest-quartile" than "higher- quartiles" patients (p = 0.0003). A secondary
      meta-analysis revealed significantly higher mortality in "lowest-tertile" than
      "mid-tertile" patients (p = 0.01) and in "lowest-tertile" than "highest-tertile"
      patients (p = 0.01). A gender-stratified meta-analysis showed significantly
      higher mortality in "lowest-quantile" than "higher-quantiles" patients in both
      men (p = 0.0008) and women (p = 0.01). In conclusion, low PMA, especially "lowest
      tertile/quartile" PMA, is a predictor of high all-cause mortality at midterm
      follow-up after TAVI for both men and women. However, PMA categorization into
      50th percentiles may be invalid to predict mortality.

PMID- 30098709
TI  - Proficiency-based training and credentialing can improve patient outcomes and
      decrease cost to a hospital system.
AB  - BACKGROUND: While proficiency-based robotic training has been shown to enhance
      skill acquisition, no studies have shown that training leads to improved outcomes
      or quality measures. METHODS: Board-certified general surgeons participated in an
      optional proficiency-based robotic training curriculum and outcomes from robotic
      hernia cases were analyzed. Multivariable analysis was performed for operative
      times to adjust for patient and surgical variables. RESULTS: Six out of 16 (38%)
      surgeons completed training and 210 robotic hernia cases were analyzed. Longer
      operative times were associated with bilateral repairs (observed-to-expected
      operative time ratio [OTR] = 1.41, p < 0.001) and incarceration (OTR = 1.24, p =
      0.006), while female patients (OTR = 0.87, p = 0.001) and increasing chronologic
      case order (OTR = 0.94, p < 0.001) were associated with shorter operative times.
      Surgeons who completed robotic training achieved shorter OTRs than those who did
      not (p = 0.03). Comparing non-risk adjusted hospital costs, trainees had an
      average of $1207 in savings (20% reduction) per robotic hernia case. CONCLUSIONS:
      A structured proficiency-based robotics training curriculum is an effective way
      to reduce operative times and costs.

PMID- 30098710
TI  - The New World Health Organization Classification for Pancreatic Neuroendocrine
      Neoplasia.
AB  - Based on the 2010 version, the 2017 World Health Organization (WHO 2017)
      classification is for pancreatic neuroendocrine neoplasms (PanNEN). The WHO 2017
      classification introduces the novel well-differentiated neuroendocrine tumor of
      high grade (NET G3). A sharp distinction between NET and poorly differentiated
      neuroendocrine carcinoma (NEC) is emphasized to highlight substantial biological
      differences. Further changes comprise the definition of mixed neuroendocrine non
      neuroendocrine neoplasm (MiNEN), to accommodate all grades of both neoplasm
      components, and the abolition of preneoplastic lesions given their rarity in the
      pancreas. The 2017 American Joint Cancer Committee classification (AJCC 2017)
      adopts such a classification for all digestive sites.

PMID- 30098711
TI  - Liquid Biopsies for Neuroendocrine Tumors: Circulating Tumor Cells, DNA, and
      MicroRNAs.
AB  - Effective management of neuroendocrine tumors depends on early diagnosis,
      personalized risk stratification, and monitoring response to therapy. During
      cancer progression, tumors shed circulating tumor cells, circulating tumor DNA,
      and microRNAs into the bloodstream. Analysis of these biomarkers offers the
      prospect of a liquid biopsy to predict/monitor therapeutic responses, assess drug
      resistance, and quantify residual disease. Compared with single-site biopsies,
      these entities have the potential to inform intratumor heterogeneity and tumor
      evolution in a reproducible and less invasive way. This article summarizes the
      state-of-the-art on the potential role of these markers as prognostic and
      predictive factors in neuroendocrine tumors.

PMID- 30098712
TI  - The NETest: The Clinical Utility of Multigene Blood Analysis in the Diagnosis and
      Management of Neuroendocrine Tumors.
AB  - The neuroendocrine neoplasms test (NETest) is a multianalyte liquid biopsy that
      measures neuroendocrine tumor gene expression in blood. This unique signature
      precisely defines the biological activity of an individual tumor in real time.
      The assay meets the 3 critical requirements of an optimal biomarker: diagnostic
      accuracy, prognostic value, and predictive therapeutic assessment. NETest
      performance metrics are sensitivity and specificity and in head-to-head
      comparison are 4-fold to 10-fold more accurate than chromogranin A. NETest
      accurately identifies completeness of surgery and response to somatostatin
      analogs. Clinical registry data demonstrate significant clinical utility in
      watch/wait programs.

PMID- 30098713
TI  - Novel Functional Imaging of Neuroendocrine Tumors.
AB  - Somatostatin receptor imaging constitutes an integral part in neuroendocrine
      tumor visualization and should, because of its vastly superior performance, use
      68Ga-DOTA-somatostatin analogue-PET/computed tomography rather than scintigraphy;
      it is particularly valuable for detecting metastases to lymph nodes, bone,
      peritoneum, and liver, which may be missed by morphologic imaging. 18FDG
      PET/computed tomography is better suited for G3 and high-G2 neuroendocrine
      tumors. 18FDG-PET/computed tomography provides prognostic information.
      Alternative available PET tracers are 18F-DOPA and 11C-5-hydroxytryptophan. To
      take full advantage of the technique PET/computed tomography should include
      diagnostic intravenous contrast-enhanced computed tomography. PET/MRI is
      currently mainly investigational.

PMID- 30098714
TI  - Molecular Genetic Studies of Pancreatic Neuroendocrine Tumors: New Therapeutic
      Approaches.
AB  - Pancreatic neuroendocrine tumors (PNETs) arise sporadically or as part of
      familial syndromes. Genetic studies of hereditary syndromes and whole exome
      sequencing analysis of sporadic NETs have revealed the roles of some genes
      involved in PNET tumorigenesis. The multiple endocrine neoplasia type 1 (MEN1)
      gene is most commonly mutated. Its encoded protein, menin, has roles in
      transcriptional regulation, genome stability, DNA repair, protein degradation,
      cell motility and adhesion, microRNA biogenesis, cell division, cell cycle
      control, and epigenetic regulation. Therapies targeting epigenetic regulation and
      MEN1 gene replacement have been reported to be effective in preclinical models.

PMID- 30098715
TI  - When and How to Use Somatostatin Analogues.
AB  - Long-acting depot formulations of the currently available somatostatin analogues
      are considered the first-line treatment for control of hormonal excess by hormone
      producing neuroendocrine tumors of the gastrointestinal tract and pancreas. These
      drugs are currently also considered the first-line treatment for tumor control of
      both hormone-producing and non-hormone-producing neuroendocrine tumors of the
      gastrointestinal tract and pancreas. These drugs need coupling and interaction
      with specific somatostatin receptor subtypes, which are expressed on the cells of
      neuroendocrine tumors of the gastrointestinal tract and pancreas.

PMID- 30098716
TI  - New Treatments for the Carcinoid Syndrome.
AB  - Neuroendocrine tumors, including carcinoids, are rare and insidiously growing
      tumors. Related to their site of origin, tumors can be functional, causing
      various forms of the carcinoid syndrome, owing to the overproduction of
      serotonin, histamine, or other bioactive substances. They often invade adjacent
      structures or metastasize to the liver and elsewhere. Treatment includes
      multimodal approaches, including cytoreductive surgery, locoregional
      embolization, cytotoxic therapy, peptide receptor radionuclide therapy, and
      various targeted therapies with goals of symptom relief and control of tumor
      growth. This article summarizes current and emerging approaches to management and
      reviews several promising future therapies.

PMID- 30098718
TI  - Current Chemotherapy Use in Neuroendocrine Tumors.
AB  - The role of chemotherapy in neuroendocrine tumors (NETs) has evolved with the
      development of other effective systemic therapies. At the same time, the evolving
      classification of NETs by grade has allowed for prognostic stratification.
      Chemotherapy is not routinely used for grade 1 to 2 NETs, but capecitabine
      (CAPTEM) or streptozocin-based regimens may be used, particularly for pancreatic
      NETs. In contrast, poorly differentiated grade 3 NETs are usually treated with
      platinum doublet chemotherapy. There is no consensus for the treatment of well
      differentiated G3 NETs, but platinum doublets or CAPTEM are reasonable options.

PMID- 30098719
TI  - Peptide Receptor Radiotherapy Comes of Age.
AB  - Peptide receptor radionuclide therapy is a form of systemic radiotherapy shown to
      be effective in treating neuroendocrine tumors expressing somatostatin receptors.
      The NETTER-1 trial was the first randomized phase III clinical trial evaluating a
      radiolabeled somatostatin analog, and demonstrated significant improvement in
      progression-free survival among patients with midgut neuroendocrine tumors
      treated with 177Lu-DOTATATE versus high-dose octreotide. This article discusses
      the evolution of peptide receptor radionuclide therapy, side effects, and
      potential future treatment approaches.

PMID- 30098720
TI  - Surgical Approaches to the Management of Neuroendocrine Liver Metastases.
AB  - Surgical approaches to hepatic metastases occupy an important role in the
      management of patients with neuroendocrine neoplasms and may have curative or
      palliative intentions. Resection of hepatic disease with curative intent is the
      only modality offering potential cure for patients with liver metastases;
      however, only a minority of patients are eligible. Regardless of resection
      margin, disease recurrence almost invariably occurs and novel
      adjuvant/neoadjuvant therapies are mandated to be included within multimodal
      treatment concepts. Liver transplantation in meticulously selected patients may
      be associated with excellent outcomes, but unfortunately demands on donated
      organs limit the wider utilization of this approach.

PMID- 30098721
TI  - Gastric Carcinoids.
AB  - Gastric carcinoids, formally named gastric neuroendocrine neoplasms (NENs), are
      derived from enterochromaffin-like cells of the stomach and are increasingly
      diagnosed. A majority are designated as type I (related to autoimmune gastritis)
      and type II (related to gastrinoma) neoplasms that develop secondary to gastrin
      hypersecretion. Types I and II gastric carcinoids are mostly small-sized (1-2
      cm), multiple, low-malignancy potential lesions mainly confined to the gastric
      mucosa/submucosa. These lesions have an indolent course and low metastatic
      potential. In contrast, type III gastric carcinoids are single, larger-sized (>2
      cm), non-gastrin-related lesions that infiltrate the muscular layers associated
      with local and distant metastases.

PMID- 30098722
TI  - The Problem of Appendiceal Carcinoids.
AB  - Appendiceal neuroendocrine neoplasms are uncommon, mostly discovered
      coincidentally during appendectomy. They usually show a benign clinical course
      and appendectomy alone is curative. However, some cases may harbor malignant
      potential; therefore, additional/prophylactic operations, such as right
      hemicolectomy, are offered. Current international guidelines are based on
      heterogeneous and retrospective series. Thus, there is lack of robust evidence,
      mainly in terms of accurate factors, that could identify patients at risk,
      requiring more extensive surgical treatment. In this article, we highlight
      controversies in the epidemiology, workup assessment, and management algorithms
      of appendiceal neuroendocrine neoplasms, but also to explore future developments
      and advances.

PMID- 30098717
TI  - Gastrinomas: Medical or Surgical Treatment.
AB  - This article reviews the role of surgical and medical management in patients with
      Zollinger-Ellison syndrome (ZES) due to a gastrin-secreting neuroendocrine tumor
      (gastrinoma). It concentrates on the status at present but also briefly reviews
      the changes over time in treatment approaches. Generally, surgical and medical
      therapy are complementary today; however, in some cases, such as patients with
      ZES and multiple endocrine neoplasia type 1, the treatment approach remains
      controversial.

PMID- 30098723
TI  - Carcinoid Heart Disease: A Review.
AB  - Carcinoid heart disease remains a major cause of morbidity and mortality among
      patients with carcinoid syndrome and metastatic neuroendocrine tumors. Screening
      of all patients with N-terminal pro-B-type natriuretic peptide and transthoracic
      echocardiography is critical for early detection, as early symptoms and signs
      have low sensitivity for the disease. Cardiac surgery, in appropriate cases, is
      the only definitive therapy for advanced carcinoid heart disease, and it improves
      patient symptoms and survival. Management of carcinoid heart disease is complex,
      and multidisciplinary assessment of cardiac status, hormonal syndrome, and tumor
      burden is critical in guiding optimal timing of surgery.

PMID- 30098724
TI  - The Problem of High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms: Well
      Differentiated Neuroendocrine Tumors, Neuroendocrine Carcinomas, and Beyond.
AB  - High-grade gastroenteropancreatic neuroendocrine neoplasms are well
      differentiated neuroendocrine tumors or poorly differentiated small/large cell
      neuroendocrine carcinoma. Distinguishing these entities relies on different
      genetic backgrounds and resulting different biology. The new classification
      creates several problems. Almost all clinical treatment data on neuroendocrine
      neoplasms do not stratify between well and poorly differentiated, providing
      insufficient help in treatment selection. Treatment of gastroenteropancreatic
      neuroendocrine neoplasms should separate between well-differentiated
      neuroendocrine tumors and neuroendocrine carcinoma, and depends on primary tumor
      site, stage, proliferation rate, and clinical course. This article addresses how
      to diagnose and treat gastroenteropancreatic neuroendocrine neoplasms, focusing
      on well-differentiated neuroendocrine tumors versus neuroendocrine carcinomas.

PMID- 30098726
TI  - The Genesis of the Neuroendocrine Tumors Concept: From Oberndorfer to 2018.
AB  - The concept of neuroendocrine tumors (NETs) began in the 1900s with Oberndorfer's
      description of carcinoid tumors, followed by specific cytotoxic agents and the
      identification of somatostatin. NETs diagnosis was confirmed by World Health
      Organization classification. Histopathology included immunohistochemistry with
      specific antibodies. Imaging was refined with molecular imaging. Somatostatin is
      the leading agent for controlling clinical symptoms related to hormone
      production. Increasing interest in these tumors, previously thought rare, led to
      increased incidence and prevalence. Between 1960 and 1970, the true NET-concept
      was established with development of radioimmunoassays for peptides and hormones,
      and imaging with computerized tomography.

PMID- 30098725
TI  - Lung and Thymic Carcinoids.
AB  - Carcinoids of the lung and thymus are rare thoracic cancers. In general, lung
      carcinoid tumors have a favorable prognosis, particularly when diagnosed at an
      early stage and treated with surgical resection. Thymic neuroendocrine tumors may
      be associated with multiple endocrine neoplasia-1 syndrome, tend to have a more
      aggressive natural history, and relatively frequently secrete ectopic
      adrenocorticotropic hormone.

PMID- 30098727
TI  - Management of Neuroendocrine Tumors in the Twenty-First Century.

PMID- 30098728
TI  - NET-Working for the Future.

PMID- 30098729
TI  - The Unfolded State of the C-Terminal Domain of L9 Expands at Low but Not at
      Elevated Temperatures.
AB  - The temperature dependence of the overall dimensions of the denatured state
      ensemble (DSE) of proteins remains unclear. Some studies indicate compaction of
      the DSE at high temperatures, whereas others argue that dimensions do not
      decrease. The degree of compaction or expansion in the cold-denatured state has
      been less studied. To investigate the temperature dependence of unfolded state
      dimensions, small angle x-ray scattering measurements were performed in native
      buffer in the absence of denaturant for a designed point mutant of the C-terminal
      domain of L9, a small cooperatively folded alpha-beta protein, at 14 different
      temperatures over the range of 5-60 degrees C. The I98A mutation destabilizes the
      domain such that both the DSE and the folded state are populated at 25 degrees C
      in the absence of denaturant or extreme pH. Thermal unfolding as well as cold
      unfolding can thus be observed in the absence of denaturant, allowing a direct
      comparison of these regimes for the same protein using the same technique. The
      temperature of maximal stability, Ts, is 30 degrees C. There is no detectable
      change in Rg of the unfolded state as the temperature is increased above Ts, but
      a clear expansion is detected as the temperature is decreased below Ts. The Rg of
      the DSE populated in buffer was found to be 27.8 +/- 1.7 A at 5 degrees C, 21.8
      +/- 1.9 A at 30 degrees C, and 21.7 +/- 2.0 A at 60 degrees C. In contrast, no
      significant temperature dependence was observed for the value of Rg measured in 6
      M guanidine hydrochloride. The small angle x-ray scattering data reported here
      indicate clear differences between the cold- and thermal-unfolded states and show
      that there is no significant compaction at elevated temperatures.

PMID- 30098730
TI  - Determination of trace water contents of organic solvents by gas chromatography
      mass spectrometry-selected ion monitoring.
AB  - This paper describes the development of a novel gas chromatography-mass
      spectrometry-selected ion monitoring (GC/MS-SIM) method for the determination of
      trace water contents of organic solvents, using the characteristic m/z 18, m/z
      17, and m/z 16 ions of H2O as the qualitative ion and the m/z 18 ion as the
      quantifier ion. The accuracy and precision of this method were validated. An
      excellent linear correlation was obtained for trace water contents between 0 and
      0.5217 wt%, with a correlation coefficient (R2) of 0.9999, in addition to spike
      recoveries of 82.6-112.6%, and relative standard deviations (n = 6) of 0.4-7.2%.
      The limit of detection (S/N = 3) and limit of quantitation (S/N = 10) for the
      trace water contents of organic solvents were 0.0005% wt% and 0.0016% wt%,
      respectively.The analytical results confirmed that this method was useful for
      determining the trace water contents of organic solvents, because it has a low
      detection limit and wide linear range. It requires only small amounts of the
      samples and enables sample batch analysis. It is very environmentally friendly
      and saves reagents.

PMID- 30098731
TI  - Dual-opposite end multiple injection method applied to sequential determination
      of Na+, K+, Ca+2, Mg+2 ions and free and total glycerol in biodiesel by capillary
      zone electrophoresis.
AB  - A novel method for the sequential determination of sodium, potassium, calcium,
      and magnesium and free and total glycerol in biodiesel by capillary zone
      electrophoresis is proposed herein. The inorganic cations were separated along an
      effective length of 43.5 cm. The samples to quantify the free and total glycerol
      were injected into the opposite capillary end, close to the detection window,
      with an effective length of 8.5 cm. It was possible to achieve the separation of
      six analytes within 3 min. The quantification limits for the cations and glycerol
      ranged from 0.071 to 0.5 mg kg-1 to and 0.0017% to 0.017% w/w, respectively.
      Despite the complexity of the injection steps, the values for the instrumental,
      intraday and interday precision were better than 2.13, 4.49 and 5.68% (RSD),
      respectively, for the cations and the free and total glycerol. The method has
      good accuracy and specificity, which was statistically confirmed through an
      interlaboratory assay, where the method was compared with official methods.

PMID- 30098732
TI  - Regression algorithm for calculating second-dimension retention indices in
      comprehensive two-dimensional gas chromatography.
AB  - Gas chromatography-mass spectrometry (GC-MS) is one of the most accurate, well
      developed, and reliable analytical tools for the analysis of volatile and
      semivolatile compounds. The GC-MS data have been extensively improved by
      enhancing the separation capacity via comprehensive two-dimensional gas
      chromatography (GC * GC). The reliability of the identification of the analytes
      in GC * GC-MS can be notably improved by applying the second-dimension retention
      index (2I) as additional analytical parameter along with the commonly used first
      dimension retention index (1I) and mass spectrum. A novel approach for
      calculating second-dimension retention indices (2I) for semivolatile organic
      compounds is proposed. It is noteworthy that the standards used in calculations
      are the same compounds recommended as internal standards by US EPA 8270 Method
      for analysis of semivolatile organic compounds. The new algorithm takes into
      account the analyte retention time and its retention temperature at the secondary
      column, (2tR) and (2TR), respectively. The experimental data collected with
      different primary oven temperature ramp rates and carrier gas flow rates have
      shown that the calculated by the proposed approach 2I values remain the same for
      each evaluated compound, drifting in a very narrow range. The proposed approach
      was tested using 100 organic compounds from various chemical classes including
      alkanes, phenols, nitrobenzenes, chlorinated hydrocarbons, anilines, polycyclic
      aromatic hydrocarbons (PAHs), phthalates, etc. The important advantage of the
      proposed 2I values for compounds of the same chemical origin (reference standards
      and analytes) involves applicability of well-known Lee's indices for non-polar
      phases. Therefore, the proposed approach can be used in targeted and non-targeted
      analysis of a wide range of organic compounds. The reduced version of the second
      dimension retention indices provides a valuable mapping of the homologues series
      of organic compounds, making their detection and identification easy and
      reliable.

PMID- 30098733
TI  - Application of cellulose 3,5-dichlorophenylcarbamate covalently immobilized on
      superficially porous silica for the separation of enantiomers in high-performance
      liquid chromatography.
AB  - Our earlier studies have demonstrated the applicability of polysaccharide-based
      chiral selectors in combination with superficially porous (or core-shell) silica
      (SPS) particles for the preparation of highly efficient chiral stationary phases
      (CSP). In earlier studies, CSPs were prepared by coating (adsorption) of the
      chiral selector onto the surface of silica. In this study we report for the first
      time the CSP obtained by covalent immobilization of a chiral selector onto the
      surface of SPS particles. The applicability of this CSP for the separation of
      enantiomers in pure methanol and acetonitrile, as well as in n-hexane/2-propanol
      mobile phases is shown. The effect of the injected sample amount, mobile phase
      flow rate and detection frequency on separation performance were studied, as well
      as high efficiency separation of enantiomers with the analysis time less than 30
      s was attempted.

PMID- 30098734
TI  - Gas chromatographic-based techniques for the characterization of low molecular
      weight carbohydrates and phenylalkanoid glycosides of Sedum roseum root
      supplements.
AB  - An extensive characterization of low molecular weight carbohydrates (LMWC) and
      phenylalkanoid glycosides (PAG) of Sedum roseum root supplements has been carried
      out for the first time by gas chromatography coupled to mass spectrometry (GC-MS)
      and by comprehensive two-dimensional gas chromatography coupled to time-of-flight
      mass spectrometry (GC * GC-ToF MS). Optimization of the required derivatization
      procedure for improved determination of PAG showed the combined use of
      trimethylsilylimidazole and trimethylchlorosilane as the most appropriate
      reagents. Up to 37 compounds were qualitative- and quantitatively characterized
      in different dietary supplements of S. roseum by GC-MS. In addition to the well
      known rosin, rosarin, rosavin and salidroside, other carbohydrates, polyalcohols,
      acids, etc. were determined. Among them, several seven-carbon monosaccharides
      such as coriose and 2,7-anhydro-beta-d-altro-heptulose were detected for the
      first time in S. roseum root supplements. Sedoheptulose was found to be the most
      abundant compound (9-151 mg g-1), followed by rosiridin (20-81 mg g-1) and
      rosavin (11-56 mg g-1). The use of GC * GC-ToF MS allowed the detection and
      tentative assignation of 48 additional compounds mainly belonging to the
      phenylalkanoid glycoside, pentosyl-hexose and hexosyl-hexose families.

PMID- 30098735
TI  - Summary of the 2016 International Surviving Sepsis Campaign: A Clinician's Guide.
AB  - The Surviving Sepsis Campaign: International Guidelines for Management of Sepsis
      and Septic Shock: 2016 provides updated recommendations, rationales, and evidence
      tables for best care of patients with sepsis. "Sepsis is a life-threatening organ
      dysfunction caused by a dysregulated host response to infection. Septic shock
      (sepsis-3) is a subset of sepsis with circulatory and cellular/metabolic
      dysfunction associated with a higher risk of mortality than with sepsis alone."
      Sepsis and septic shock are major health care problems, affecting millions of
      people around the world each year. Early identification and management of sepsis
      and septic shock in the initial hours after sepsis develops, improves outcomes.

PMID- 30098736
TI  - Early Administration of Intravenous Fluids in Sepsis: Pros and Cons.
AB  - Fluid resuscitation in the management of patients with sepsis and severe sepsis
      has been considered the standard of care for almost 2 decades. The rationale for
      fluid resuscitation is related to improvement in cardiac output and organ
      perfusion. Recent research evidence challenges the use of fluid resuscitation in
      patients diagnosed with sepsis. Research is needed to determine the timing of
      fluid administration, as well as the volume and type of fluid to achieve positive
      patient outcomes. This article discusses the pros and cons of early fluid
      administration in the management of patients with sepsis.

PMID- 30098737
TI  - Beyond the Intensive Care Unit: Posttraumatic Stress Disorder in Critically Ill
      Patients.
AB  - Medical care progress has enabled more patients in the intensive care unit to
      survive critical illnesses and return to daily living. This shift in survival
      rates has shed new light on the emotional consequences this experience. For
      patients surviving an ICU stay, posttraumatic stress disorder has been identified
      in approximately 9% to 27% compared with 7% of the general US population.
      Practitioners have an important role to play in early identification of patients
      experiencing signs and symptoms of this disorder. Timely interventions and
      treatment may reduce the incidence of physical and psychological comorbid
      conditions.

PMID- 30098738
TI  - Emerging Adjunctive Approach for the Treatment of Sepsis: Vitamin C and Thiamine.
AB  - Evidence is emerging that parenteral administration of high-dose vitamin C and
      thiamine may be a beneficial adjuvant therapy of severe sepsis and septic shock.
      Despite modern practices in critical care medicine, sepsis and severe sepsis
      remain a leading cause of morbidity and mortality in the critical care unit.

PMID- 30098739
TI  - Hit or Miss? A Review of Early-Onset Sepsis in the Neonate.
AB  - For the bedside nurse identifying at-risk neonates for development of early-onset
      sepsis is a challenge. The ambiguity of clinical presentation can easily be
      overlooked, resulting in delayed treatment of this vulnerable population. Adding
      to this dilemma is inconsistent implementation of screening criteria used by
      health providers to identify at-risk neonates, resulting in lost opportunities of
      early identification and treatment. This article discusses the current approach
      to and the nurse's role in early-onset sepsis.

PMID- 30098740
TI  - Simulation to Manage the Septic Patient in the Intensive Care Unit.
AB  - Sepsis and septic shock are complex, clinical conditions associated with high
      morbidity and mortality rates. There are evidence-based guidelines outlining
      priority care areas for sepsis, including early screening outside the intensive
      care unit. Nurses are directly involved with patient care and must be able to
      provide safe, competent care after graduation. High-fidelity human patient
      simulation is an educational tool that provides access to a safe learning
      environment where the care of a septic patient can be experienced. Nurses can
      gain confidence and knowledge surrounding the care of the septic patient while
      improving patient care outcomes.

PMID- 30098741
TI  - Cardiogenic Shock in the Septic Patient: Early Identification and Evidence-Based
      Management.
AB  - Sepsis-induced cardiogenic shock is a lethal condition and the management of it
      is challenging. Cardiogenic shock in the septic patient involves myocardial
      systolic and diastolic dysfunction. The limited ability of the ventricles to
      contract effectively results in a decrease in oxygen delivery to the organs and
      tissues. Supportive therapy is provided to patients with sepsis and no specific
      drug can reverse the myocardial dysfunction. Rapid diagnosis, prompt antibiotic
      therapy, cautious protocol-driven fluid resuscitation and vasoactive agents,
      control of infectious source, and expeditious coronary artery revascularization
      is recommended to achieve a positive outcome.

PMID- 30098742
TI  - Hospital Costs Associated with Sepsis Compared with Other Medical Conditions.
AB  - Sepsis is a condition that has become a main focus for health care organizations
      owing to the alarming cost of caring for patients, as well as the disturbing
      mortality rates, that accompany this condition. Sepsis is one of the costliest
      conditions billed to all payer groups: Medicare, Medicaid, private insurance, and
      uninsured patients. Health care organizations have implemented multiple
      strategies and best practices to improve the outcomes of patients with a
      diagnosis of sepsis.

PMID- 30098743
TI  - Special Considerations for the Septic Patient Going to the Operating Room.
AB  - Perioperative care of the septic patient presents unique challenges for the
      nurse. Understanding the physiology of sepsis is important for the nurse to
      anticipate the physiologic changes associated with the disorder and to prioritize
      the patient's needs. Ensuring adequate intravenous access by peripheral or
      central venous access as well as anticipating potential invasive monitoring lines
      allows the nurse to quickly administer antibiotic therapy, initiate fluid
      resuscitation, and prepare for potential vasopressor use.

PMID- 30098744
TI  - Early Identification and Management of the Septic Patient in the Emergency
      Department.
AB  - Sepsis and septic shock affect millions of people around the globe and kills more
      than 1 in 4 patients worldwide. Emergency departments (EDs) nationwide have
      implemented evidence-based protocols to facilitate the early detection and
      treatment of patients with sepsis. Despite these efforts, patients present to the
      ED undifferentiated and can often have an unclear source of infection. The latest
      literature provides refined definitions and clinical criteria for sepsis
      identification and indicates that early detection combined with the appropriate
      early management improves the septic patients' morbidity and mortality rates.

PMID- 30098745
TI  - Sepsis in the Obstetric Client.
AB  - Maternal sepsis is the third most common direct cause of maternal mortality
      following maternal hemorrhage and maternal hypertension. Undetected and poorly
      managed maternal infections can lead to sepsis, death, or disability for the
      mother and an increased likelihood of early neonatal infection and other adverse
      outcomes. When caring for obstetric patients, it is important to identify the
      stages of antepartum, intrapartum, and postpartum care. Sepsis occurs at any
      stage of obstetric care.

PMID- 30098746
TI  - Sepsis in the Burn Patient.
AB  - Sepsis is the leading cause of death in burn patients. Interventions are
      challenging owing to a lack of specific guidelines. All burn types involve a risk
      for complications. Interventions should include care of the burn, medication
      administration, continuous monitoring for infection development, infection
      prevention measures, and (if necessary) treatment of sepsis. Sepsis in burn
      patients is different from the unburned population. Efforts are needed to develop
      more accurate diagnostic strategies and guidelines to trigger rapid treatment via
      specific sepsis bundles.

PMID- 30098747
TI  - Sepsis: Special Considerations, Management, and Treatment for Diverse Patient
      Populations.

PMID- 30098748
TI  - Menstrual Cycle Effects on Sleep.
AB  - Subjective and objective sleep changes occur during the menstrual cycle. Poorer
      sleep quality in the premenstrual phase and menstruation is common in women with
      premenstrual symptoms or painful menstrual cramps. There is increased sleep
      spindle activity from follicular to luteal phase, potentially progesterone
      related. Luteal phase changes also include blunted temperature rhythm amplitude
      and reduced rapid eye movement sleep. Women with polycystic ovary syndrome should
      be screened for sleep disordered breathing. Short sleep duration is associated
      with irregular menstrual cycles, which may impact reproductive health. Menstrual
      cycle phase and menstrual-related disorders should be considered when assessing
      women's sleep complaints.

PMID- 30098749
TI  - Impact of Shift Work on the Circadian Timing System and Health in Women.
AB  - Women who do shift work are a sizable part of the workforce. Shift workers
      experience circadian misalignment due to shifted sleep periods, with potentially
      far-reaching health consequences, including elevated risk of sleep disturbances,
      metabolic disorders, and cancer. This review provides an overview of the
      circadian timing system and presents the sex differences that can be observed in
      the functioning of this system, which may account for the lower tolerance to
      shift work for women compared with men. Recent epidemiologic findings on female
      specific health consequences of shift work are discussed.

PMID- 30098750
TI  - Sleep Health in Pregnancy: A Scoping Review.
AB  - Using scoping review methodology, this article investigates the literature on
      sleep duration, continuity/efficiency, timing, daytime sleepiness/alertness, and
      perceived sleep quality in each trimester of a healthy pregnancy. Data suggest
      significant variability in sleep between women, with less evidence to support
      major changes in sleep health across trimesters. There is a need for further
      research on this topic to better inform women and their health providers.

PMID- 30098751
TI  - Management Strategies for Restless Legs Syndrome/Willis-Ekbom Disease During
      Pregnancy.
AB  - Restless legs syndrome/Willis-Ekbom disease is a common disorder during pregnancy
      that may significantly impact on the health of affected women, leading to
      negative consequences in the short and long term. An accurate diagnosis helps to
      recognize the syndrome and choose the optimal therapeutic strategy, based on the
      characteristics and needs of the patient. This article summarizes the main
      treatment options recommended by the consensus clinical guidelines of the
      International Restless Legs Syndrome Study Group and provides a short guide to
      the management of restless leg syndrome during pregnancy in clinical practice.

PMID- 30098752
TI  - Sleep-Disordered Breathing in Pregnancy.
AB  - Sleep-disordered breathing (SDB) in pregnancy can present as snoring and/or
      obstructive sleep apnea (OSA), and the prevalence is increasing due to the
      increase in maternal obesity. Pregnant women often present with fatigue and
      daytime sleepiness rather than the classic symptoms. Habitual snoring, older age,
      chronic hypertension, and high prepregnancy body mass index are reliable
      indicators of increased risk for SDB and should trigger further testing. The gold
      standard for diagnosis of OSA is an overnight laboratory polysomnography.
      Although there are no studies linking SDB to poor fetal outcomes, fetal well
      being remains paramount throughout the course of pregnancy.

PMID- 30098753
TI  - The Role of Circadian Rhythms in Postpartum Sleep and Mood.
AB  - Women often experience sleep disturbances and worsening sleep quality throughout
      pregnancy and postpartum. Circadian rhythms are closely linked to sleep problems
      and mood disorders. This systematic review provides a summary of studies of
      circadian rhythms and associated sleep problems and maternal distress, among
      postpartum women. Articles were idenitfied through a systematic literature
      search. Circadian rhythm disturbances were strongly correlated with depression,
      social factors and mothers's exposure to light postpartum. Future research should
      include larger, prospective studies as well as randomized controlled trials for
      measuring effect of circadian rhythm interventions on postpartum mental health
      outcomes.

PMID- 30098754
TI  - Sleep in Women with Chronic Pain and Autoimmune Conditions: A Narrative Review.
AB  - Chronic pain and sleep disturbances are intricately intertwined. This narrative
      review provides comments on observations related to pain, stress-immunity, and
      sleep. Sleep evidence is reviewed from studies of select conditions involving
      pain (ie, functional somatic syndromes and autoimmune) that are predominant in
      women. Chronic pain and poor sleep encompass persistent stress-immune activation
      with systemic inflammation, cellular oxidative stress, and sick behavior
      indicators that increase morbidity and threaten quality of life. In painful
      conditions, sleep impairments are nearly ubiquitous, and exaggerated combined
      effects should not be underestimated or ignored, nor should crucial implications
      for clinical practice and research.

PMID- 30098755
TI  - Effects of Exercise on Sleep in Women with Breast Cancer: A Systematic Review.
AB  - Sleep deficiency is common and distressing for women with breast cancer
      throughout the care continuum. This article describes the scope and quality of
      evidence related to exercise interventions to improve sleep in women with breast
      cancer. Fifteen studies met the criteria and 12 were judged to be excellent
      quality. The most frequent intervention was walking, primarily during the time of
      chemotherapy. Eleven studies reported postintervention improvement in sleep
      deficiency. Most yoga, qigong, and dance intervention studies reported no
      differences between groups. Emerging evidence exists for the effectiveness of
      aerobic exercise to improve various sleep outcomes in women with breast cancer.

PMID- 30098756
TI  - Impact of Traumatic Stress on Sleep and Management Options in Women.
AB  - After exposure to traumatic stress, women are at greater risk than men for
      developing symptoms of some psychiatric disorders, including insomnia and
      nightmares. Sleep disturbance is one of the most refractory symptoms of
      posttraumatic stress disorder. Women were included in a few studies that examined
      efficacy of psychological or pharmacologic interventions for trauma-related sleep
      disturbances. Studies demonstrated preliminary evidence for efficacy of cognitive
      behavioral therapy for insomnia, imagery rehearsal therapy, and combinations of
      these techniques in treating insomnia and nightmares in trauma-exposed women.
      Prazosin as an adjunct to ongoing treatment is a potentially efficacious strategy
      for treating trauma-related nightmares in women.

PMID- 30098757
TI  - Sleep Disorders in Women Veterans.
AB  - Sleep disorders are common among women veterans and contribute to poor
      functioning and quality of life. Studies show that women veterans are
      particularly prone to insomnia, sleep-disordered breathing, and insufficient
      sleep. Standard cognitive behavioral therapy for insomnia (CBT-I) should be
      viewed as first-line therapy for insomnia disorder, and women veterans should be
      screened and treated for sleep-disordered breathing. Behavioral and lifestyle
      factors contributing to insufficient sleep should also be addressed. Challenges
      exist in diagnosing and treating sleep disorders in women veterans, in part
      because of high rates of psychiatric comorbidities, such as posttraumatic stress
      disorder and depression.

PMID- 30098760
TI  - Sleep and Women's Health Across the Lifespan.

PMID- 30098761
TI  - Evaluation of patient safety and satisfaction in a program of ambulatory
      laparoscopic cholecystectomy program with expanded criteria.
AB  - INTRODUCTION: The good results obtained with the implementation of ambulatory
      laparoscopic cholecystectomy programs have led to the expansion of the initial
      inclusion criteria. The main objective was to evaluate the results and the degree
      of satisfaction of the patients included in a program of laparoscopic
      cholecystectomy without admission, with expanded criteria. METHODS: Observational
      study of a cohort of 260 patients undergoing ambulatory laparoscopic
      cholecystectomy between April 2013 and March 2016 in a third level hospital. We
      classified the patients into 2groups based on compliance with the initial
      inclusion criteria of the outpatient program. Group I (restrictive criteria)
      includes 164 patients, while in group ii (expanded criteria) we counted 96
      patients. We compared the surgical time, the rate of failures in ambulatory
      surgery, rate of conversion, reinterventions and mortality and the satisfaction
      index. RESULTS: The overall success rate of ambulatory laparoscopic
      cholecystectomy was 92.8%. The most frequent cause of unexpected income was for
      medical reasons. There was no statistically significant difference between the
      2groups for total surgery time, the rate of conversion to open surgery and the
      number of major postoperative complications Do not demostrate differences in
      surgical time, nor in the number of perioperative complications (major
      complications 1,2%), or the number of failures in ambulatory surgery, nor the
      number of readmissions between both groups. There was no death. 88.5% of patients
      completed the survey, finding no differences between both groups in the patient
      satisfaction index. The overall score of the process was significantly better in
      group ii(P=.023). CONCLUSIONS: Ambulatory laparoscopic cholecystectomy is a safe
      procedure with a good acceptance by patients with expanded criteria who were
      included in the surgery without admission program.

PMID- 30098759
TI  - Impact of Poor Sleep on Physical and Mental Health in Older Women.
AB  - Many aspects of sleep and circadian rhythms change as people age. Older adults
      usually experience decrease in sleep duration and efficiency, increase in sleep
      latency and fragmentation, high prevalence of sleep disorders, and weakened rest
      activity rhythms. Research evidence suggests that women are more likely to report
      aging-related sleep problems. This review presents epidemiologic and clinical
      evidence on the relationships between sleep deficiency and physical and mental
      outcomes in older women, explores potential mechanisms underlying such
      relationships, points out gaps in the literature that warrant future
      investigations, and considers implications in clinical and public health
      settings.

PMID- 30098758
TI  - Sleep and Sleep Disorders in the Menopausal Transition.
AB  - The menopausal transition is associated with an increase in insomnia symptoms,
      especially difficulty staying asleep, which negatively impacts quality of life.
      Vasomotor symptoms are a key component of sleep disruption. Findings from
      polysomnographic studies are less consistent in showing disrupted sleep in
      menopausal transition independent of aging; further prospective studies are
      needed. Hormone therapy alleviates subjective sleep disturbances, particularly if
      vasomotor symptoms are present. However, because of contraindications, other
      options should be considered. Further work is needed to develop preventive and
      treatment strategies for alleviating sleep disturbances to ensure better health,
      quality of life, and productivity in midlife women.

PMID- 30098762
TI  - The short-term prognostic value of C-reactive protein in elderly patients with
      acute heart failure.
AB  - INTRODUCTION AND OBJECTIVES: Plasma c-reactive protein (crp) has been tested as a
      prognostic marker in acute heart failure (ahf). Whether its measurement really
      provides significant prognostic information when applied to elderly patients with
      ahf episodes remains unclear. METHODS: We measured the plasma crp values of
      patients admitted because of any type of ahf to internal medicine services. We
      evaluated the association of these values with the patients' baseline clinical
      characteristics and their 3-month posdischarge all-cause mortality or readmission
      rates. For comparison purposes, we divided the sample in tertiles of low, medium
      and high crp values (<2,24mg/l, 2,25-11,8mg/l and>11,8mg/l). RESULTS: We included
      1443 patients with a median age of 80 years (interquartile range 73-85); 680
      (47%) were men, with a moderate comorbid burden. 60.1% had preserved left
      ventricular ejection fraction (> 50%). Multivariate analysis confirmed an
      independent association between higher crp values and the presence of respiratory
      infection, lower systolic blood pressure and deteriorated renal function upon
      admission. Three months after the index admission, a total of 142 patients (9.8%)
      had died, and 268 (18.6%) had either been readmitted or died. admission crp
      values did not correlate with 3-month all-cause mortality (P=0.79), 3-month all
      cause readmission (P=0.96) or the combination of both events (P=0.96). However,
      higher crp values were associated with a longer length of stay (P<0.001).
      CONCLUSION: Our study does not confirm an association between admission plasma
      crp values in elderly ahf patients and subsequent higher 3-month mortality or
      readmission risks.

PMID- 30098763
TI  - Metabolic signature of squamous cell carcinoma of the head and neck: Consequences
      of TP53 mutation and therapeutic perspectives.
AB  - There is a pressing need to identify ways of sensitising squamous cell carcinomas
      of the head and neck (SCCHN) to the effects of current treatments, both from
      oncological and functional perspectives. Alteration to cellular metabolism is now
      widely considered a hallmark of the cancer phenotype; presents a potentially
      attractive therapeutic target in this regard; and as such has received renewed
      research interest in recent years. However, whilst metabolic disruption may occur
      to some degree in all tumours, there is undoubtedly heterogeneity and detailed
      study of individual tumour types is paramount if effective therapeutic strategies
      targeting metabolism are to be developed and effectively deployed. In this review
      we outline current understanding of altered tumour metabolism and how these
      adaptations promote tumorigenesis generally. We relate this specifically to SCCHN
      by focusing on several recent key studies specific to SCCHN, and by discussing
      the role TP53 mutation may play in this metabolic switch, given the fundamental
      role of this oncogenic event in SCCHN tumorigenesis. Finally, we also offer
      insight into the potential therapeutic implications this may have in the clinical
      setting and make recommendations for future study.

PMID- 30098765
TI  - Impact of obesity on outcomes for patients with head and neck cancer.
AB  - OBJECTIVES: The prognostic role of obesity in head and neck squamous cell
      carcinoma (HNSCC) is not well defined. This study aims to determine its effect on
      disease-specific outcomes such as recurrence-free survival (RFS), locoregional
      recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) in
      addition to overall survival (OS). METHODS: For patients with newly diagnosed
      HNSCC undergoing radiation therapy (RT) at a single institution, body mass index
      (BMI) at diagnosis was categorized as normal (18.5 to 24.9 kg/m2), overweight (25
      to 29.9 kg/m2) and obese (>=30 kg/m2). Outcomes were compared by BMI group using
      Cox regression. RESULTS: 341 patients of median age 59 (range, 20-93) who
      underwent curative RT from 2010 to 2017 were included. 58% had oropharynx cancer,
      17% larynx and 15% oral cavity. 72% had stage IVA/B disease and 28% stage I-III.
      At diagnosis, 33% had normal BMI, 40% overweight, and 28% obese. 59% had
      definitive RT and 41% had postoperative RT. Alcoholic/smoking status, advanced
      tumor stage, hypopharynx/larynx tumors, and feeding tube placement were more
      common in patients with lower BMI (P < .05 for each). Median follow-up was 30
      months (range, 3-91). Higher BMI was associated with improved OS (P < .05) and
      obesity was associated with longer RFS (P < .05) and DMFS (P < .05), but not
      LRRFS (P = .07) after adjusting for confounding variables. CONCLUSION: Being
      overweight/obese at the time of HNSCC diagnosis is an independent prognostic
      factor conferring better survival, while obesity is independently associated with
      longer time to recurrence, primarily by improving distant control.

PMID- 30098766
TI  - A prospective analysis of prevalence of metastasis in levels IIB and V neck nodes
      in patients with operable oral squamous cell carcinoma.
AB  - OBJECTIVES: The present study was designed to know and analyze the prevalence of
      pathological involvement of level IIB and V neck nodes in operable oral cavity
      squamous cell carcinomas. MATERIALS AND METHODS: All treatment naive, willing
      biopsy proven patients of age group 18-70 years with oral cavity squamous cell
      carcinomas undergoing surgery from May 2015 to December 2016 in a single tertiary
      care Institute were prospectively analyzed for level IIb and V involvement.
      RESULTS: A total of 199 patients met the selection criteria of the study. Most
      common site was buccal mucosa, majority were cT2 lesions and 90% underwent
      Modified neck dissection. 63% of patients had pN0 disease. The rate of
      involvement of level II b and V nodes was 3% and was associated with higher T
      size, disease burden in proximal basin and lymphovascular invasion. There was no
      skip metastasis to level IV. Only one patient had skip metastasis to levels V and
      IIB each. CONCLUSION: To conclude our data strongly supports omission of level
      IIb and level V nodal dissection routinely in patients with cT1 and T2 buccal
      cancers. However, a randomized controlled study to evaluate the morbidity as well
      as recurrence pattern between the selective and super-selective approach is
      warranted.

PMID- 30098767
TI  - The course of sexual interest and enjoyment in head and neck cancer patients
      treated with primary (chemo)radiotherapy.
AB  - INTRODUCTION: The aim of this prospective study was to investigate the course of
      sexual interest and enjoyment in relation to sociodemographic and clinical
      factors, health-related quality of life (HRQOL), and symptoms of psychological
      distress in head and neck cancer (HNC) patients treated with primary
      (chemo)radiotherapy. METHODS: HNC patients (n = 354) completed patient-reported
      outcome measures (PROMs) on HRQOL (EORTC QLQ-C30 and QLQ-H&N35, including the
      sexuality subscale covering less sexual interest and enjoyment), and
      psychological distress (HADS) pretreatment, at 6-week follow-up and at 3-, 6-, 12
      , 18-, and 24-month follow-up (i.e., after treatment). Linear mixed models were
      used to analyze the course of sexuality from pretreatment to 24-month follow-up,
      and to investigate its relation to sociodemographic and clinical factors, HRQOL,
      and psychological distress as measured at baseline, and to investigate the course
      of sexuality from 6- to 24-month follow-up in relation to these factors measured
      at 6-month follow-up. RESULTS: Before start of treatment, 37% of patients
      reported having less sexuality, which increased to 60% at 6-week follow-up, and
      returned to baseline level from 12-month follow-up onwards. Older age (p = 0.037)
      and trouble with social contact (p < 0.001), weight loss (p = 0.013), and
      constipation (p = 0.041) before treatment were associated with less sexuality
      over time. Female gender (p = 0.021) and poor social functioning (p < 0.001) at 6
      month follow-up were associated with less sexuality from 6- to 24-month follow
      up. DISCUSSION: Less sexuality is often reported in HNC patients treated with
      (chemo)radiotherapy. Using PROMs in clinical practice may help identify patients
      who might benefit from supportive care targeting sexuality.

PMID- 30098764
TI  - Emergency department visits and unplanned hospitalizations in the treatment
      period for head and neck cancer patients treated with curative intent: A
      population-based analysis.
AB  - BACKGROUND: Mucosal head and neck squamous cell cancers are often managed with
      multimodality treatment which can be associated with significant toxicity. The
      objective of this study was to assess emergency department visits and unplanned
      hospitalizations for these patients during and immediately after their treatment.
      METHODS: A cohort of patients treated for head and neck squamous cell carcinoma
      was developed using administrative data. Emergency department visits and
      hospitalizations in the 90-day post-treatment period was determined. If a second
      treatment was initiated prior to the completion of 90 days, the attributable risk
      period was changed to the second treatment. RESULTS: Cohort of 3898 patients
      (1312 larynx/hypopharynx; 2586 oral cavity/oropharynx) from 2008 to 2012. The
      number of unplanned hospitalizations or ED visits (per 100 patient days) were
      0.69 for surgery, 0.78 for surgery followed by concurrent chemoradiotherapy
      (CCRT), 0.55 for surgery followed by radiotherapy, 0.86 for CCRT, and 0.50 for
      radiation. Patients receiving CCRT had a statistically higher likelihood of
      treatment period events. The larynx/hypopharynx cancer subsite, higher
      comorbidity and more advanced stage of disease were all independent predictors of
      events. CONCLUSIONS: Patients undergoing treatment for head and neck cancer have
      significant unplanned hospitalizations and visits to the emergency department in
      the treatment period. Rates are higher in patients receiving CCRT. Quality
      improvement interventions should be used to improve these rates.

PMID- 30098768
TI  - Pattern of and survival following loco-regional and distant recurrence in
      patients with HPV+ and HPV- oropharyngeal squamous cell carcinoma: A population
      based study.
AB  - OBJECTIVES: The incidence of human papillomavirus (HPV) positive oropharyngeal
      squamous cell carcinoma (OPSCC) is increasing. Currently, data is sparse on the
      pattern and timing of recurrence. This long-term study concerning both HPV- and
      p16-status aimed to report predictive factors, pattern, timing of loco-regional
      recurrence (LRR) and distant recurrence (DR), and survival following recurrence
      in patients diagnosed with OPSCC. MATERIAL AND METHODS: We included patients
      diagnosed with OPSCC from 2000 to 2014 in Eastern Denmark, who were treated with
      curative intent. Tumors were defined as HPV-positive when they were both HPV-DNA
      and p16-positive. Time-to-failure and -death were estimated by the Kaplan-Meier
      method. Cox proportional hazards models were used to evaluate predictors of
      failure. RESULTS: The cohort consisted of 1244 consecutive patients with OPSCC of
      which 288 patients (23%) experienced recurrence. Of these patients, the majority
      (n = 197/1244; 16%) experienced LRR and the remaining (n = 91/1244; 7%) DR.
      Significantly more HPV-negative patients experienced recurrence (n = 170/486;
      35%) compared to HPV-positive patient (n = 112/726; 15%). DR occurred for both
      groups predominantly to the lung (n = 63/91; 69.2%) followed by the liver and
      bone. Factors influencing risk of LRR included gender, T-classification, and HPV
      status. The same variables influenced risk of DR in addition to the UICC-8
      classification, N-classification, pack years of smoking, and performance status.
      HPV-status was the strongest risk factor for LRR and DR. CONCLUSION: LRR and DR
      occur significantly less often in HPV-positive patients compared with HPV
      negative patients. HPV-status is an independent and strong predictor of
      recurrence. DR most commonly occurs to the lungs, irrespective of HPV-status.

PMID- 30098769
TI  - Gastro-omental free flap for reconstruction of tongue defects.
AB  - OBJECTIVES: The purpose of this paper is to report the technique and outcomes of
      the use of gastro-omental free flap reconstruction in glossectomy defects.
      MATERIALS AND METHODS: This is a prospective case series of 9 patients of tongue
      squamous cell carcinoma, who underwent either subtotal or partial glossectomy and
      reconstruction with gastro-omental free flap. The flap anatomy, surgical
      technique and the outcomes including the swallowing and speech are presented.
      RESULTS: Five patients underwent partial glossectomy and 4 had sub-total
      glossectomy. The median age was 43 years; and the median follow up was 11.4
      months. Laparoscopic harvest was done in 8 patients. There was one flap loss.
      Seven patients underwent postoperative radiotherapy. Functional evaluation was
      done in 5 patients who were disease free. Four could tolerate soft diet orally,
      one patient was on liquid to pureed diet. Speech was intelligible in 4. None of
      the patients had any complications related to laparotomy or laparoscopy.
      CONCLUSION: Gastro-omental flap provided a secretory mucosal surface and was
      beneficial in the saliva depleted patients post radiotherapy. The laparoscopic
      harvest of this flap has minimized donor site morbidity. One patient had a flap
      loss. Two patients reported superficial ulcerations on the surface, one of them
      had to undergo surgical debulking to correct it while the other healed with
      conservative measures. Speech and swallowing outcomes of the reconstructed tongue
      was good, especially in patients with partial glossectomy. The reconstructed
      gastric mucosal flaps tolerated the adjuvant radiation well.

PMID- 30098770
TI  - Validation and assessment of discordance of the 8th edition AJCC (American Joint
      Committee on Cancer) clinical and pathologic staging systems in patients with
      p16+ oropharyngeal cancer treated with surgery and adjuvant radiation at a single
      institution.

PMID- 30098771
TI  - Oropharyngeal cancer is no longer a disease of younger patients and the
      prognostic advantage of Human Papillomavirus is attenuated among older patients:
      Analysis of the National Cancer Database.
AB  - OBJECTIVES: HPV-positive oropharyngeal cancer (OPC) patients have been observed
      to be younger than patients with HPV-negative OPC at diagnosis. We evaluated
      recent trends in age at OPC diagnosis, and whether older age attenuates the
      survival benefit of HPV-positive tumor status. MATERIALS AND METHODS: Patients
      diagnosed with OPC from 2004 to 2014 represented in the National Cancer Database
      were included. HPV tumor status was available after 2010. Trends in age by
      calendar year were compared using linear regression. Overall survival was
      compared using Cox Proportional Hazards models. RESULTS: The mean age of OPC
      patients (N = 119,611) increased significantly from 2004 to 2014 (beta = 0.21
      years of age per calendar year, 95% confidence interval [CI] = 0.19-0.23). The
      increase in age from 2010 to 2014 was similar for HPV-positive (N = 21,880; beta
      = 0.63, 95%CI = 0.53-0.72) and HPV-negative (N = 11,504; beta = 0.59, 95%CI =
      0.45-0.74) patients. Between 2010 and 2014, the proportion of OPCs that were HPV
      positive increased significantly for all age groups, including for patients >=70
      years old (from 45% to 60%, ptrend < 0.001). Although patients >=70 years with
      HPV-OPC had improved survival compared to those with HPV-negative OPC (adjusted
      hazard ratio [aHR] = 0.65, 95%CI = 0.55-0.76), the survival benefit of HPV
      positive tumor status was significantly attenuated compared to younger HPV-OPC
      patients (50-59 years: aHR = 0.45, 95%CI = 0.39-0.51; pinteraction < 0.001).
      CONCLUSION: The age at OPC diagnosis is increasing for both HPV-positive and HPV
      negative patients, and a rising proportion of older patients have HPV-positive
      tumors. These findings dispel the notion that HPV-positive OPC is a disease of
      younger patients, identify a growing elderly population of HPV-positive OPC
      patients with reduced survival, and have implications for evolving treatment
      paradigms.

PMID- 30098772
TI  - Perioperative considerations in free flap surgery: A review of pressors and
      anticoagulation.
AB  - Given the high stakes for microvascular reconstruction, the majority of
      reconstructive surgeons have developed paradigms for pre, intra, and
      postoperative management that have proven to result in individual high success
      rates. Much has been done to identify and avoid perioperative factors that could
      potentially increase flap failure rates. Two example of this practice has been
      the generalized use of anticoagulation in free tissue transfer and the
      prohibition against vasopressor use in patients that are undergoing free tissue
      transfer. This manuscript will discuss these issues.

PMID- 30098773
TI  - Reconstruction Special Edition, Issue 3.

PMID- 30098775
TI  - Vanderbilt head and neck symptom survey, version 2.0: Clinical and research
      utility for identification of symptom clusters and changes in symptoms over time.
AB  - OBJECTIVES: The symptoms and functional defects following treatment for head and
      neck cancer (HNC) have been poorly defined. The purpose of this study was to
      examine the utility of the Vanderbilt Head and Neck Symptom Survey (VHNSS)
      version 2.0 to identify symptom clusters experienced by patients with HNC as well
      as assess reliability and sensitivity to change. MATERIALS AND METHODS: The VHNSS
      2.0 questionnaire was completed by 150 patients over three studies. Two studies
      utilized the survey at multiple time points. RESULTS: Cluster analysis identified
      ten multi-item clusters and three single items. The internal consistency was good
      to excellent, with Cronbach's alpha coefficient above 0.90 in five symptom
      clusters and above 0.70 in remaining clusters. Clusters demonstrated convergent
      and divergent validity with other measures. Symptom burden was lowest at
      baseline, peaked at the end of treatment then subsided over the following months.
      CONCLUSIONS: The VHNSS 2.0 is a reliable and valid measure of acute and late
      toxicities in patients treated for HNC. The tool may be used in research and
      clinical practice to screen, to evaluate treatments, and to compare side effects
      of treatment regimens.

PMID- 30098774
TI  - A mixed methods examination of distress and person-centred experience of head and
      neck lymphoedema.
AB  - PURPOSE: This study aimed to examine the course and nature of distress and
      quality of life (QoL) during and after head and neck lymphoedema (HNL) treatment
      in people who developed HNL following treatment for head and neck cancer (HNC).
      METHODS: This study (n = 10) used a mixed method explanatory design to explore
      distress associated with HNL. Component 1 used a prospective repeated measures
      design to examine distress during a 22-week HNL program. Component 2 used a
      qualitative interview approach to understand the patient experience of distress
      after completion of HNL treatment. RESULTS: During the HNL program distress
      associated with HNL significantly reduced from baseline to week 6 (p = 0.015),
      and baseline to week 22 (p = 0.007). There were no significant differences in
      QoL, body image or fear of cancer progression over time. Self-reported presence
      of HNL significantly reduced from baseline to week 6 (p = 0.02), week 6 to week
      22 (p = 0.026), and from baseline to week 22 (p = 0.001). Qualitative interviews
      using thematic analysis following HNL treatment, revealed 6 major themes
      associated with the experiences of distress related to HNL - psychological
      impact; physical appearance and pattern/timing; experience of receiving
      treatment; day to day impact; supports that helped manage distress; and
      adjustment to a new normal. CONCLUSIONS: This study found that distress
      associated with cancer treatment-related HNL may reduce with the delivery of a
      HNL program. Interview data following completion of the HNL treatment identified
      several themes related to HNL and its relationship with distress, function and
      day-to-day life. CLINICAL TRIAL REGISTRATION: HREC/12/QPAH/295.

PMID- 30098777
TI  - The impact of unplanned reoperations in head and neck cancer surgery on survival.
AB  - OBJECTIVES: Unplanned reoperation causes physical and psychological stress in
      patients and it costs more in terms of medical, economic and social resource. The
      purpose of the study was to evaluate the incidence, risk factors and clinical
      significance of unplanned reoperation (any unscheduled surgery within 30 days
      from the initial surgery) in patients who had undergone head and neck cancer
      (HNC) surgery. MATERIALS AND METHODS: A total of 574 consecutive patients who had
      received surgery for HNC with or without flap reconstruction from 2010 to 2015
      were analyzed. Clinical and biochemical characteristics, cause of unplanned
      reoperation, cancer subsites, and previous treatment history were compared
      between unplanned reoperation group (n = 60) and control group (n = 514).
      Multivariable analyses were performed to identify risk factors for unplanned
      reoperation. Clinical significance was evaluated by multivariable survival
      analyses using Cox proportional hazard model. RESULTS: Overall rate of unplanned
      reoperation was 10.5%. Flap complication (40.0%) was the most common cause,
      followed by infection (16.7%), necrosis (11.7%), and bleeding (8.3%). Higher N
      (N2) classification, long operation time and previous treatment before surgery
      were identified as risk factors for unplanned reoperation. Based on multivariable
      survival analyses, recurrence-free survival was significantly decreased in
      unplanned reoperation group (Hazard ratio = 1.85, 95% confidence interval [1.23
      2.80]), but not overall survival. CONCLUSION: Unplanned reoperation significantly
      decreased recurrence-free survival in patients with HNC surgery. Thus, careful
      surgical/ perioperative management is needed to reduce unplanned reoperation in
      HNC patients with advanced nodal disease, long operation time or previous
      treatment history.

PMID- 30098776
TI  - Frequent HPV-independent p16/INK4A overexpression in head and neck cancer.
AB  - OBJECTIVES: p16INK4A (p16) is the most widely used clinical biomarker for Human
      Papillomavirus (HPV) in head and neck squamous cell cancer (HNSCC). HPV is a
      favourable prognostic marker in HNSCC and is used for patient stratification.
      While p16 is a relatively accurate marker for HPV within the oropharynx, recent
      reports suggest it may be unsuitable for use in other HNSCC subsites, where a
      smaller proportion of tumors are HPV-driven. MATERIALS AND METHODS: We integrated
      reverse phase protein array (RPPA) data for p16 with HPV status based on
      detection of viral transcripts by RNA-seq in a set of 210 HNSCCs profiled by The
      Cancer Genome Atlas project. Samples were queried for alterations in CDKN2A, and
      other pathway genes to investigate possible drivers of p16 expression. RESULTS:
      While p16 levels as measured by RPPA were significantly different by HPV status,
      there were multiple HPV (-) samples with similar expression levels of p16 to HPV
      (+) samples, particularly at non-oropharyngeal subsites. In many cases, p16
      overexpression in HPV (-) tumors could not be explained by mutation or
      amplification of CDKN2A or by RB1 mutation. Instead, we observed enrichment for
      inactivating mutations in the histone H3 lysine 36 methyltransferase, NSD1 in HPV
      (-)/p16-high tumors. CONCLUSIONS: RPPA data suggest high p16 protein expression
      in many HPV (-) non-oropharyngeal HNSCCs, limiting its potential utility as an
      HPV biomarker outside of the oropharynx. HPV-independent overexpression of wild
      type p16 in non-oropharyngeal HNSCC may be linked to global deregulation of
      chromatin state by inactivating mutations in NSD1.

PMID- 30098778
TI  - MicroRNA-based classifiers for diagnosis of oral cavity squamous cell carcinoma
      in tissue and plasma.
AB  - BACKGROUND: MicroRNAs (miRNAs) hold promise as diagnostic cancer biomarkers. Here
      we aimed to define the miRNome in oral squamous cell carcinoma (OSCC) and normal
      oral mucosa (NOM), and to identify and validate new diagnostic miRNAs and miRNA
      combinations in formalin-fixed paraffin-embedded (FFPE) tissue samples and plasma
      samples. METHODS: We performed next-generation miRNA sequencing in FFPE tissue
      samples of OSCC (n = 80) and NOM (n = 8). Our findings were validated by
      quantitative polymerase chain reaction (qPCR) analysis of OSCC (n = 195) and NOM
      (n = 103) FFPE tissue samples, and plasma samples from OSCC patients (n = 55) and
      healthy persons (n = 18). RESULTS: The OSCC miRNome included 567 miRNAs, 66 of
      which were differentially expressed between OSCC and NOM. Using qPCR data, we
      constructed receiver operating curves to classify patients as NOM or OSCC based
      on miRNA combinations. The area under the curve was of 0.92 from FFPE tissue (miR
      204-5p, miR-370, miR-1307, miR-193b-3p, and miR-144-5p), and 1.0 from plasma
      samples (miR-30a-5p and miR-769-5p). Model calibration and discrimination were
      evaluated using 10-fold cross-validation. CONCLUSIONS: Analysis of the miRNome
      from many OSCC cases improves our knowledge of the importance of individual
      miRNAs and their predictive potential in OSCC. We successfully identified miRNA
      classifiers in FFPE OSCC tissue and plasma with a high discriminatory ability
      between OSCC and NOM. The proposed combination of miR-30a-5p and miR-769-5p in
      plasma from OSCC patients could serve as a minimal invasive biomarker for
      diagnosis and control of T-site recurrences.

PMID- 30098779
TI  - Swallowing beyond six years post (chemo)radiotherapy for head and neck cancer; a
      cohort study.
AB  - OBJECTIVE: The objective of this prospective study is to report on long-term
      swallowing outcomes in a group of head and neck cancer patients following (chemo)
      radiotherapy treatment, assess for changes over time and identify any predictor
      variables of outcome. MATERIALS AND METHODS: 42 survivors were assessed on four
      swallowing measures and followed up from pre-treatment to six years post 3D
      (chemo) radiotherapy. Measures included a swallowing specific QOL questionnaire,
      penetration-aspiration scale, dietary restrictions and a timed water swallow
      test. RESULTS: At six years, 71% reported swallowing difficulties on the
      questionnaire. One fifth of patients had aspiration, with a raised risk of chest
      infection. Seven percent required a laryngectomy for a dysfunctional larynx.
      Despite this, half the group reported having a normal diet. There was variation
      in the pattern of change between one and six years. A significant deterioration
      was only observed in the timed water swallow test (p < 0.0001). Larger
      radiotherapy volume predicted this outcome. None of the variables tested
      predicted outcome for the other three swallow measures. CONCLUSION: Patients
      continue to report swallowing difficulties at six years, with a proportion having
      persistent aspiration. Further work on identifying the risk factors associated
      with aspiration tolerance, aspiration pneumonia, prevention and management is
      warranted. Long-term dysphagia remains a significant and serious concern
      following (chemo) radiotherapy for HNC and swallowing outcomes should continue to
      be monitored over time.

PMID- 30098780
TI  - Risk and survival of patients with medullary thyroid cancer: National
      perspective.
AB  - BACKGROUND: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor account
      for 1-2% of thyroid cancer. In this study, we aim to examine the characteristics
      and survival of patients with MTC. METHODS: A retrospective cohort study
      utilizing the National Cancer Data Base, 2004-2014. The study population included
      adults with either MTC (cases) or with differentiated thyroid cancer (DTC)
      (controls). RESULTS: A total of 2,776 MTC and 171,631 DTC patients were included.
      The median follow-up time for MTC was 55.5 months (interquartile range: 31.2-84.6
      months). As compared to DTC, patients with MTC were more likely to be >= 45-year
      old, male, and Black (p < 0.001). Neck dissection improved survival in patients
      with stage III [HR: 0.26, 95%CI: (0.10, 0.64), p = 0.004]. In patients with
      stages I and II, neck dissections did not add significant survival benefit to
      thyroidectomy [stage I, HR: 1.00, 95%CI: (0.54, 1.86), p = 0.99],[stage 2, HR:
      0.72, 95%CI: (0.40, 1.29), p = 0.27]. However, neck dissections upgraded staging
      to N1A and N1B in 17.7% and 14.3% of patients with clinically N0 neck,
      respectively. In stage IV, thyroidectomy with neck dissection had the highest 5
      year survival (84.9%), but this was not significantly different from
      thyroidectomy alone (84.1%); Patients who had thyroidectomy and EBRT with or
      without neck dissection had a lower survival than thyroidectomy alone (p < 0.01).
      CONCLUSIONS: Neck dissection performed on patients with clinically N0 neck, is
      important for accurate staging and associate with improved survival in advanced
      stages. Thyroidectomy and neck dissection in stage IV not only have palliative
      role but also add survival advantage.

PMID- 30098782
TI  - Nomogram for preoperative prediction of nodal extracapsular extension or positive
      surgical margins in oropharyngeal squamous cell carcinoma.
AB  - INTRODUCTION: Extracapsular extension (ECE) in regional lymph nodes and positive
      surgical margins (PSM) are considered high-risk adverse pathologic features in
      patients with oropharyngeal squamous cell carcinoma (OPSCC) that each constitute
      an indication for postoperative adjuvant chemoradiation. We identify pre
      operative clinical factors that can predict post-operative ECE and/or PSM and
      create a nomogram to help clinical decision making. METHODS: Adult patients with
      non-metastatic OPSCC with initial surgical treatment and confirmed HPV status
      diagnosed between 2010 and 2014 were selected from the National Cancer Database.
      Clinical staging was modified to American Joint Committee on Cancer 8th edition
      parameters. Logistic regression was used for multivariate analysis to identify
      predictors of pathologic ECE and/or PSM. RESULTS: 5065 patients were included.
      47.5% of the 3336 HPV-positive (HPV+) patients had ECE/PSM. 40.4% of the 1729 HPV
      negative (HPV-) patients with had ECE/PSM. A model was built that included age,
      clinical ECE, tumor grade, and clinical T and N staging for HPV+ patients.
      Increasing N-classification was highly predictive of pathologic ECE and/or PSM
      (N1 OR = 3.6, N2 OR = 7.0, N3 OR = 11.2, p < 0.01). Clinical ECE (OR = 4.1, p <
      0.01), tumor grade (ORs 2.2-4.4 with p < 0.05), and increasing clinical T
      classification (ORs 1.2-1.8, p < 0.05) were also associated with ECE and/or PSM.
      A similar model was built for HPV- with similar predictive capability. Two
      internally validated nomograms were designed that demonstrated good
      discrimination (HPV+ AUC = 0.66, 95% CI: 0.64-0.68, and HPV- AUC = 0.70, 95% CI:
      0.67-0.72) and good calibration (goodness-of-fit statistic of HPV+ 6.32, p = 0.61
      and HPV- 11.66, p = 0.17). CONCLUSIONS: These are the first nomograms designed to
      help predict ECE or PSM for both HPV+ and HPV- OPSCC. The nomograms can
      facilitate shared decision-making between clinicians and patients as they
      consider upfront treatment selection for OPSCC.

PMID- 30098781
TI  - Adverse effects of chemotherapy on the teeth and surrounding tissues of children
      with cancer: A systematic review with meta-analysis.
AB  - OBJECTIVE: The aim of this systematic review was to assess evidence on dental
      adverse effects associated with chemotherapy (CH) administered to children with
      cancer. MATERIAL AND METHODS: Eight databases were searched without restrictions
      up to March 2017 for studies reporting on dental effects of CH administered for
      childhood cancer. After elimination of duplicates, data extraction, and risk of
      bias assessment according to the Cochrane guidelines, random-effects meta
      analyses of Relative Risks (RR) and Mean Differences (MD) and their 95%
      Confidence Intervals (CI) were performed, followed by meta-regression and
      sensitivity analyses. RESULTS: The literature search identified a total of 15 non
      randomized case-control studies including at least 2315 patients (mean age at
      diagnosis or CH of 6.6 years; 36% male) followed for up to 22.9 years after CH.
      Meta-analysis indicated that CH was associated with increased risk for tooth
      agenesis compared to healthy controls (RR = 2.47; 95% CI = 1.30-4.71; P = 0.006).
      This translated to every seventh child with CH having agenesis of at least one
      tooth that would not otherwise have. Additionally, CH was significantly
      associated with increased risk of tooth discoloration, arrested tooth
      development, enamel hypoplasia, microdontia, premature apexification, and
      decreased salivary flow rate, as well as worse oral hygiene and greater caries
      experience compared to controls. However, the strength of evidence was very low
      due to the inclusion of non-randomized study designs with high risk of bias.
      CONCLUSIONS: Current evidence from childhood cancer survivors indicates that
      chemotherapy is associated with considerable dental adverse effects that might be
      associated with greater burden of disease and treatment costs.

PMID- 30098784
TI  - Risk of plate removal in free flap reconstruction of the mandible.
AB  - OBJECTIVES: To evaluate the factors associated with need for removal of fixation
      plates in mandibular free flap reconstruction. METHODS: This retrospective cohort
      analysis reviews patients undergoing mandibular free flap reconstruction at a
      tertiary care center from 2005 to 2016. Patients requiring removal of fixation
      plates were identified through electronic medical records. Factors including
      demographics, adjuvant therapy, surgical site infection (SSI) and fistula rates
      were compared. Removal rates based on flap type were determined. RESULTS: Between
      2004 and 2016, 307 patients underwent osteocutaneous mandibular free flap
      reconstruction. 83 required removal of their fixation plates (27%). Age, tobacco
      use, and BMI were similar between patients requiring removal versus not requiring
      removal. Primary indications for removal were plate exposure (n = 41), and/or
      chronic drainage (n = 31), infection (n = 25), and pain (n = 17). Patients
      undergoing removal were significantly more likely to have had adjuvant radiation
      therapy (OR 2.09, CI 1.82-3.81), surgical site infection (OR 13.9, CI 5.15-43.2),
      and post-operative fistula (OR 13.0, 6.85-24.8). 35% of all fibula flaps (n =
      52), 21% of osteocutaneous radial forearm (n = 21), and 11% of osteocutaneous
      scapular flaps (n = 6) required removal. 90% of patients (n = 75) had resolution
      of their symptoms following hardware removal. CONCLUSION: Surgical site infection
      and fistula are strongly associated with the need for plate removal. Fibular free
      flaps carry the highest rate of plate removal. Plate removal leads to resolution
      of plate-associated symptoms in a majority of cases.

PMID- 30098785
TI  - Prognostic and clinicopathological significance of cyclin D1 expression in oral
      squamous cell carcinoma: A systematic review and meta-analysis.
AB  - OBJECTIVES: To evaluate the prognostic significance of cyclin D1 (CD1)
      overexpression in OSCC. MATERIAL AND METHODS: We searched studies published
      before August 2017 (Pubmed, Embase, Web of Science, Scopus). We evaluated the
      quality of the studies included (Quality in Prognosis Studies [QUIPS] tool). The
      impact of CD1 overexpression on overall survival and disease-free survival, T
      status, N status, stage, and histological degree was meta-analyzed. We analyzed
      heterogeneity among studies, conducted sensitivity analyses, analyzed small-study
      effects, and conducted subgroup analyses. RESULTS: 31 studies (2942 patients) met
      inclusion criteria. Qualitative evaluation demonstrated that not all studies were
      performed with the same rigor, finding the greatest risk of bias in the study
      confounding domain. Quantitative evaluation showed that CD1 overexpression had a
      strong statistical association with worse overall survival (HR = 2.00, 95% CI =
      1.59-2.51, p < 0.001), worse disease-free survival (HR = 1.46, 95% CI = 1.13
      1.87, p = 0.003), higher T status (OR = 1.51, 95% CI = 1.07-2.13, p = 0.02), N+
      status (OR = 2.16, 95% CI = 1.60-2.92, p < 0.001), advanced stage (OR = 1.44, 95%
      CI = 1.15-1.81, p = 0.002), and high histological grade (OR = 1.60, 95% CI = 1.12
      2.29, p = 0.010). We observed heterogeneity in all parameters except for disease
      free survival and clinical stage. We found effect of small studies on T and N
      status. The tonguel SCC subgroup showed the strongest association between CD1
      overexpression and worse development. In addition, application of a cutoff point
      >=10% tumor cells with nuclear CD1 expression maintained most of the significant
      associations reported. CONCLUSIONS: These findings indicate that
      immunohistochemical assessment of CD1 overexpression may be useful as a
      prognostic biomarker for OSCC.

PMID- 30098783
TI  - Oncogenic drivers in 11q13 associated with prognosis and response to therapy in
      advanced oropharyngeal carcinomas.
AB  - OBJECTIVES: To identify potential molecular drivers associated with prognosis and
      response to treatment in advanced oropharyngeal squamous cell carcinomas (OPSCC).
      MATERIALS AND METHODS: Thirty-three OPSCC biopsies from untreated Brazilian
      patients were evaluated for human papilloma virus genotyping, genome wide copy
      number alterations and gene expression profiling. Data were integrated using
      CONEXIC algorithm. Validation with TCGA dataset and confirmation by RT-qPCR of
      candidate genes were performed. RESULTS: High-risk HPV positive cases, detected
      in 55% of advanced OPSCC, were associated with better outcome. Losses of 8p11.23
      p11.22, 14q11.1-q11.2 and 15q11.2, and gains of 11q13.2 and 11q13.2-q13.3 were
      detected as recurrent alterations. Gains of 3q26.31 and 11q13.2 and losses of
      9p21.3 were exclusively detected in HPV-negative tumors. Two clusters of
      expression profiles were observed, being one composed mostly by HPV positive
      cases (83%). HPV-positive enriched cluster showed predominantly immune response
      related pathways. Integrative analysis identified 10 modulators mapped in 11q13,
      which were frequently cancer-related. These 10 genes showed copy number gains,
      overexpression and an association with worse survival, further validated by TCGA
      database analyses. Overexpression of four genes (ORAOV1, CPT1A, SHANK2 and
      PPFIA1) evaluated by RT-qPCR confirmed their association with poor survival.
      Multivariate analysis showed that PPFIA1 overexpression and HPV status are
      independent prognostic markers. Moreover, SHANK2 overexpression was significantly
      associated with incomplete response to treatment. CONCLUSION: The integrative
      genomic and transcriptomic data revealed potential driver genes mapped in 11q13
      associated with worse prognosis and response to treatment, giving fundamentals
      for the identification of novel therapeutic targets in OPSCC.

PMID- 30098786
TI  - Resveratrol-induced p53 activation is associated with autophagy in mouse
      embryonic stem cells.
AB  - Resveratrol is a natural polyphenol with several therapeutic effects, in
      particular, inducing p53-dependent cell cycle arrest and/or apoptosis in tumor
      cells. Resveratrol-induced p53 activation may trigger differentiation and
      apoptosis in embryonic stem cells (ESCs). We show that resveratrol activates p53
      that is negatively regulated by SIRT1 deacetylation on Lys379 and positively by
      AMPK phosphorylation on Ser15 in mouse ESCs (mESCs). Surprisingly, the
      resveratrol-activated p53 is not associated with either G1/S cell cycle
      checkpoint or apoptosis in mESCs. Instead, it stimulates autophagy in a
      transcriptional-dependent manner involving up-regulation of dram1 gene
      expression. This study demonstrates a novel mechanism of resveratrol-dependent
      p53 activation in mESCs.

PMID- 30098788
TI  - Fenofibrate inhibits the growth of prostate cancer through regulating autophagy
      and endoplasmic reticulum stress.
AB  - Fenofibrate is a fibric acid derivative which exhibits a role of peroxisome
      proliferator-activated receptor-alpha agonist. It is widely utilized in therapy
      of hyperlipidemia and hypercholesterolemia. Its anticancer function is discovered
      in recent years. However, the role of fenofibrate in prostate cancer (PCa) is
      poorly understood. In this study, we investigated the function and mechanism of
      fenofibrate in PCa cells. Firstly, fenofibrate treated PCa cells showed more
      apoptosis compared with the control group. Further, we found that fenofibrate
      induced autophagy but finally blocked its complete flux in PCa cells through
      regulating AMPK-mTOR pathway. The intermediate metabolite from uncompleted
      autophagy induced endoplasmic reticulum stress (ER stress) via PERK and IRE1
      signalings. In vivo mice model confirmed that fenofibrate inhibited the growth of
      PCa. This study suggests that fenofibrate is an effective inhibitor of PCa by
      regulating autophagy and ER stress.

PMID- 30098787
TI  - Microglia support neural stem cell maintenance and growth.
AB  - Increasing evidence suggests that disease-associated microglia play a protective
      role in neurodegenerative diseases. Microglia are known to polarize into two
      reciprocate forms in response to external cues - inflammatory M1 state and anti
      inflammatory M2 state. These cells perform key functions in the development of
      the brain, such as circuit refinement, neurogenesis, and neuronal growth. In this
      study, we analyzed the secretion effect of microglia on neural stem/progenitor
      cell (NSPC) proliferation and differentiation. We cultured adult mouse-derived
      NSPCs in a conditioned medium from BV2 immortalized microglia without growth
      factors and evaluated their differentiation. When cultivated with BV2-derived
      soluble factors in the presence of basic fibroblast growth factor (bFGF) and
      epidermal growth factor (EGF), NSPCs were able to maintain Nestin expression and
      showed increased proliferation compared with those cells cultivated with bFGF and
      EGF only. Moreover, conditioned media from M2-polarized primary microglia,
      stimulated by IL-10/IL-13, showed supportive effect on NSPC proliferation. These
      data suggest that microglia support neural stem cell proliferation through
      secreting neuro-nutritious soluble factors.

PMID- 30098789
TI  - A novel MtHSP70-FPR1 fusion protein enhances cytotoxic T lymphocyte responses to
      cervical cancer cells by activating human monocyte-derived dendritic cells via
      the p38 MAPK signaling pathway.
AB  - OBJECTIVE: To evaluate the potential effects of recombinant mycobacterium
      tuberculosis heat shock protein 70-formyl peptide receptor 1 (MtHSP70-FPR1)
      fusion protein on human monocyte-derived dendritic cell (moDC) maturation;
      cytotoxic T lymphocyte (CTL) responses to cervical cancer (CC) cells; and the
      roles of the p38 MAPK, ERK, and JNK pathways in its transition. METHODS:
      Monocytes were positively selected with a MACS column with antiCD14 antibody
      conjugated microbeads from umbilical cord blood. MoDCs were stimulated with
      MtHSP70-FPR1, MtHSP70, a mix of MtHSP70 and FPR1, FPR1, or phosphate buffer
      solution (PBS) as control. Flow cytometry was used to analyze the surface
      molecule expression of moDCs and IFN-gamma-producing CD8+ T cells. T cell
      proliferation was assessed using [3][H]-thymidine assays. The cytotoxicity of
      moDC-activated T cells against CC cells was evaluated by MTT assays. Cytokine
      production was determined by enzyme-linked immunosorbent assay. Western blotting
      was used to investigate protein expression. RESULTS: Compared with MtHSP70,
      MtHSP70 + FPR1, FPR1, or PBS-mediated moDCs, MtHSP70-FPR1-pulsed moDCs expressed
      higher levels of CD80, CD86, CD83, HLA-DR, and CCR7; secreted more IL-12p70, TNF
      alpha and IL-1beta; and elicited stronger CTL priming and proliferation,
      resulting in an effective, HLA-I-dependent killing effect on CC cells. The p38
      MAPK, ERK, and JNK pathways were all activated in MtHSP70-FPR1-mediated moDC
      maturation, but the p38 MAPK pathway played a vital role. CONCLUSIONS: The
      excellent capability of MtHSP70-FPR1 fusion protein to induce phenotypical and
      functional maturation of moDCs and CC-specific CTL responses partly illustrates
      the potential clinical benefits of DC-based immunotherapy for CC.

PMID- 30098790
TI  - Ethical, Palliative, and Policy Considerations in Disorders of Consciousness.
AB  - This essay complements the scientific and practice scope of the American Academy
      of Neurology Guideline on Disorders of Consciousness by providing a discussion of
      the ethical, palliative, and policy aspects of the management of this group of
      patients. We endorse the renaming of "permanent" vegetative state to "chronic"
      vegetative state given the increased frequency of reports of late improvements
      but suggest that further refinement of this class of patients is necessary to
      distinguish late recoveries from patients who were misdiagnosed or in cognitive
      motor dissociation. Additional nosologic clarity and prognostic refinement is
      necessary to preclude overestimation of low probability events. We argue that the
      new descriptor "unaware wakefulness syndrome" is no clearer than "vegetative
      state" in expressing the mismatch between apparent behavioral unawareness when
      patients have covert consciousness or cognitive motor dissociation. We advocate
      routine universal pain precautions as an important element of neuropalliative
      care for these patients given the risk of covert consciousness. In medical
      decision-making, we endorse the use of advance directives and the importance of
      clear and understandable communication with surrogates. We show the value of
      incorporating a learning health care system so as to promote therapeutic
      innovation. We support the Guideline's high standard for rehabilitation for these
      patients but note that those systems of care are neither widely available nor
      affordable. Finally, we applaud the Guideline authors for this outstanding
      exemplar of engaged scholarship in the service of a frequently neglected group of
      brain-injured patients.

PMID- 30098791
TI  - Practice Guideline Update Recommendations Summary: Disorders of Consciousness:
      Report of the Guideline Development, Dissemination, and Implementation
      Subcommittee of the American Academy of Neurology; the American Congress of
      Rehabilitation Medicine; and the National Institute on Disability, Independent
      Living, and Rehabilitation Research.
AB  - OBJECTIVE: To update the 1995 American Academy of Neurology (AAN) practice
      parameter on persistent vegetative state and the 2002 case definition on
      minimally conscious state (MCS) and provide care recommendations for patients
      with prolonged disorders of consciousness (DoC). METHODS: Recommendations were
      based on systematic review evidence, related evidence, care principles, and
      inferences using a modified Delphi consensus process according to the AAN 2011
      process manual, as amended. RECOMMENDATIONS: Clinicians should identify and treat
      confounding conditions, optimize arousal, and perform serial standardized
      assessments to improve diagnostic accuracy in adults and children with prolonged
      DoC (Level B). Clinicians should counsel families that for adults, MCS (vs
      vegetative state [VS]/ unresponsive wakefulness syndrome [UWS]) and traumatic (vs
      nontraumatic) etiology are associated with more favorable outcomes (Level B).
      When prognosis is poor, long-term care must be discussed (Level A), acknowledging
      that prognosis is not universally poor (Level B). Structural MRI, SPECT, and the
      Coma Recovery Scale-Revised can assist prognostication in adults (Level B); no
      tests are shown to improve prognostic accuracy in children. Pain always should be
      assessed and treated (Level B) and evidence supporting treatment approaches
      discussed (Level B). Clinicians should prescribe amantadine (100-200 mg bid) for
      adults with traumatic VS/UWS or MCS (4-16 weeks post injury) to hasten functional
      recovery and reduce disability early in recovery (Level B). Family counseling
      concerning children should acknowledge that natural history of recovery,
      prognosis, and treatment are not established (Level B). Recent evidence indicates
      that the term chronic VS/UWS should replace permanent VS, with duration specified
      (Level B). Additional recommendations are included.

PMID- 30098792
TI  - Comprehensive Systematic Review Update Summary: Disorders of Consciousness:
      Report of the Guideline Development, Dissemination, and Implementation
      Subcommittee of the American Academy of Neurology; the American Congress of
      Rehabilitation Medicine; and the National Institute on Disability, Independent
      Living, and Rehabilitation Research.
AB  - OBJECTIVE: To update the 1995 American Academy of Neurology (AAN) practice
      parameter on persistent vegetative state and the 2002 case definition for the
      minimally conscious state (MCS) by reviewing the literature on the diagnosis,
      natural history, prognosis, and treatment of disorders of consciousness lasting
      at least 28 days. METHODS: Articles were classified per the AAN evidence-based
      classification system. Evidence synthesis occurred through a modified Grading of
      Recommendations Assessment, Development and Evaluation process. Recommendations
      were based on evidence, related evidence, care principles, and inferences
      according to the AAN 2011 process manual, as amended. RESULTS: No diagnostic
      assessment procedure had moderate or strong evidence for use. It is possible that
      a positive EMG response to command, EEG reactivity to sensory stimuli, laser
      evoked potentials, and the Perturbational Complexity Index can distinguish MCS
      from vegetative state/unresponsive wakefulness syndrome (VS/UWS). The natural
      history of recovery from prolonged VS/UWS is better in traumatic than
      nontraumatic cases. MCS is generally associated with a better prognosis than VS
      (conclusions of low to moderate confidence in adult populations), and traumatic
      injury is generally associated with a better prognosis than nontraumatic injury
      (conclusions of low to moderate confidence in adult and pediatric populations).
      Findings concerning other prognostic features are stratified by etiology of
      injury (traumatic vs nontraumatic) and diagnosis (VS/UWS vs MCS) with low to
      moderate degrees of confidence. Therapeutic evidence is sparse. Amantadine
      probably hastens functional recovery in patients with MCS or VS/UWS secondary to
      severe traumatic brain injury over 4 weeks of treatment. Recommendations are
      presented separately.

PMID- 30098793
TI  - Corrigendum to "Calcium mediates cell shape change in human peritoneal
      mesothelial cells" [Cell Calcium 72 (2018) 116-126].

PMID- 30098794
TI  - A three-dimensional (3D) organotypic microfluidic model for glioma stem cells -
      Vascular interactions.
AB  - Glioblastoma (GBM) is one of the deadliest forms of cancer. Despite many
      treatment options, prognosis of GBM remains dismal with a 5-year survival rate of
      4.7%. Even then, tumors often recur after treatment. Tumor recurrence is
      hypothesized to be driven by glioma stem cell (GSC) populations which are highly
      tumorigenic, invasive, and resistant to several forms of therapy. GSCs are often
      concentrated around the tumor vasculature, referred to as the vascular niche,
      which are known to provide microenvironmental cues to maintain GSC stemness,
      promote invasion, and resistance to therapies. In this work, we developed a 3D
      organotypic microfluidic platform, integrated with hydrogel-based biomaterials,
      to mimic the GSC vascular niche and study the influence of endothelial cells
      (ECs) on patient-derived GSC behavior and identify signaling cues that mediate
      their invasion and phenotype. The established microvascular network enhanced GSC
      migration within a 3D hydrogel, promoted invasive morphology as well as
      maintained GSC proliferation rates and phenotype (Nestin, SOX2, CD44). Notably,
      we compared migration behavior to in vivo mice model and found similar invasive
      morphology suggesting that our microfluidic system could represent a
      physiologically relevant in vivo microenvironment. Moreover, we confirmed that
      CXCL12-CXCR4 signaling is involved in promoting GSC invasion in a 3D vascular
      microenvironment by utilizing a CXCR4 antagonist (AMD3100), while also
      demonstrating the effectiveness of the microfluidic as a drug screening assay.
      Our model presents a potential ex vivo platform for studying the interplay of
      GSCs with its surrounding microenvironment as well as development of future
      therapeutic strategies tailored toward disrupting key molecular pathways involved
      in GSC regulatory mechanisms.

PMID- 30098795
TI  - Commentary for An integrative review of the literature on in-hospital worsening
      heart failure.

PMID- 30098796
TI  - Updates to IEC/AAMI ECG standards, a new hybrid standard.
AB  - The current set of IEC particular standards that pertain to electrocardiograph
      (ECG) devices, namely, 60601-2-25, 60601-2-27, and 60601-2-47, which define
      requirements and testing for the essential performance and basic safety of
      diagnostic ECG, ECG monitoring and ambulatory ECG systems, respectively. These
      standards have been harmonized with the corresponding AAMI standards, namely
      EC11, EC13 and EC38. Together these standards have been in existence for decades
      and have evolved separately even though the technology used in these three
      clinical applications is very similar. A work proposal was initiated in the
      ISO/IEC Joint Work Group 22 (JWG22), which over sees the revision of these
      standards, to update the standards by creating a single new hybrid standard. The
      goal of this work is a joint endeavor between ISO and IEC to combine the three
      separate particular standards that cover ECG device and to harmonize the similar
      requirements that are common across all three types of devices into one set of
      general requirements. The requirements that separate specific to meeting the
      intended use and essential performance for each of the 3 types of devices
      (diagnostic, patient monitoring, and ambulatory ECG recording) will continue to
      remain as separate requirements. Furthermore, manufactures of ECG devices have
      also been required to meet standards for disposable electrodes (AAMI EC12), ECG
      cables and leadwires (AAMI EC53), and arrhythmia analysis performance reporting
      (AAMI EC57). In addition to the primary goal, a secondary goal for the JW22 work
      is to also incorporate these three AAMI standards into the ECG hybrid standard.
      This paper describes the work being done and highlights key updates, and explains
      the rationale for approaches and changes being made. The Joint Work Group is
      currently in the process of updating the committee draft of the new hybrid
      standard before requesting comments from National Standard Committees
      participating in JWG22.

PMID- 30098797
TI  - Colonic CD30 positive plasmablastic plasmacytoma masquerading as anaplastic large
      cell lymphoma.

PMID- 30098798
TI  - China: The Next Pharmacy of the World?
AB  - The manufacturing success in China has not yet radiated to the pharmaceutical
      sector. Recently, China released a policy guideline to foster its follow-on drug
      industry, revealing its ambition to become a great power in the field. Here, I
      briefly discuss how this guideline may change the industry landscape, and its
      associated challenges and opportunities.

PMID- 30098799
TI  - New classification of tauopathies.
AB  - Tauopathies are a group of neurodegenerative diseases characterized by
      pathological intracellular deposits of the protein tau. Isoform composition,
      morphology and anatomical distribution of cellular tau-immunoreactivities are
      defining distinct tauopathies as molecular pathological disease entities. The
      clinical spectrum of tauopathies includes syndromes with primary motor symptoms
      and with primary cognitive dysfunction. The traditional syndrome-based
      classification is currently being complemented by a molecular-pathological
      classification. While the syndrome-based classification is helpful to select
      symptomatic therapies, and to generate clinical working hypotheses about
      underlying etiologies, the molecular-pathological classification is most
      important for the development and application of molecularly tailored disease
      modifying therapies.

PMID- 30098800
TI  - The neuropsychiatry of Gilles de la Tourette syndrome: The etat de l'art.
AB  - Gilles de la Tourette syndrome (GTS) is a chronic tic disorder characterised by
      the presence of multiple motor and vocal tics with onset during development. Tics
      are the most common hyperkinetic symptoms in childhood and co-morbid behavioural
      conditions (especially obsessive-compulsive disorder, attention-deficit and
      hyperactivity disorder, affective symptoms, and impulsivity) are present in the
      majority of patients. Although GTS is no longer considered a rare medical
      curiosity, its exact pathophysiology remains elusive. Recent research on the
      brain correlates of the subjective 'urge to tic' has highlighted the role of
      extra-motor pathways within the brain mechanisms of tic generation. Advances in
      our understanding of the pathophysiology of GTS can pave the way to the
      implementation of more effective treatment strategies for this heterogeneous
      neurobehavioral condition. Finally, the development of GTS-specific instruments
      for the assessment of health-related quality of life has allowed more
      standardised assessments across the lifespan, capturing the impact of both tics
      and behavioural co-morbidities.

PMID- 30098801
TI  - Keystone Genes.
AB  - The keystone species concept is used in ecology to describe individual species
      with disproportionately large effects on their communities. We extend this idea
      to the level of genes with disproportionately large effects on ecological
      processes. Such 'keystone genes' (KGs) would underlie traits involved in species
      interactions or causing critical biotic and/or abiotic changes that influence
      emergent community and ecosystem properties. We propose a general framework for
      how KGs could be identified, while keeping KGs under the umbrella of
      'ecologically important genes' (EIGs) that also include categories such as
      'foundation genes', 'ecosystem engineering genes', and more. Although likely
      rare, KGs and other EIGs could dominate certain ecological processes; thus, their
      discovery and study are relevant for understanding eco-evolutionary dynamics.

PMID- 30098802
TI  - Epigenetic and Cellular Diversity in the Brain through Allele-Specific Effects.
AB  - The benefits of diploidy are considered to involve masking partially recessive
      mutations and increasing genetic diversity. Here, we review new studies showing
      evidence for diverse allele-specific expression and epigenetic states in
      mammalian brain cells, which suggest that diploidy expands the landscape of gene
      regulatory and expression programs in cells. Allele-specific expression has been
      thought to be restricted to a few specific classes of genes. However, new studies
      show novel genomic imprinting effects that are brain-region-, cell-type- and age
      dependent. In addition, novel forms of random monoallelic expression that impact
      many autosomal genes have been described in vitro and in vivo. We discuss the
      implications for understanding the benefits of diploidy, and the mechanisms
      shaping brain development, function, and disease.

PMID- 30098803
TI  - Last gasp revisited.

PMID- 30098804
TI  - Deciding the fate of radial arteries: Will surgeons take matters in their own
      hands?

PMID- 30098805
TI  - Seeing through the ground-glass: Do imaging characteristics really matter?

PMID- 30098806
TI  - ACTIVE or not, high intensity is here to stay.

PMID- 30098807
TI  - Modify, simplify, apply: Do we need preclinical models for surgical innovation?

PMID- 30098808
TI  - Intolerably high risk in ascending aortic surgery.

PMID- 30098809
TI  - Excellent results up to 20 years with the Ross operation, albeit with some
      sobering.

PMID- 30098810
TI  - Controversies in the management of neonatal testicular torsion: A meta-analysis.
AB  - OBJECTIVE: This meta-analysis seeks to discern the optimal management strategy in
      neonatal testicular torsion (NTT). METHODS: Reviewed all English-language
      articles published between 2005 and 2015 in Medline/Pubmed that had a defined
      diagnosis of NTT within the first thirty days of life, and discussed specific
      surgical and nonsurgical management. Exclusion criteria were non-English
      literature, case reports, case studies, and failure to clearly describe the
      management of NTT. Data from 9 studies were analyzed, individually and together
      as pooled data, using a random effect model with a random intercept to estimate
      the pooled proportions of interest. Results are presented with 95% confidence
      interval. All analyses were done in SAS 9.4(r). RESULTS: 9 publications met
      criteria for this analysis with a total of 196 patients. Bilateral testicular
      torsions (n = 14) were less common as compared to right/left testicular torsion
      (n = 85/97). Asynchronous NTTs (n = 9) were more common than synchronous NTTs (n
      = 2). There was a higher incidence of NTT in neonates delivered by vaginal
      delivery (n = 110) as compared to those delivered by c-section (n = 25).
      Extravaginal torsion (n = 54) is far more common than intravaginal torsion (n =
      2). Full-term neonates (n = 122) have a higher incidence of NTT as compared to
      preterm neonates (n = 9). A total of 15 testicles were salvaged. Of the salvaged
      testicles 2 were documented as prenatal, 10 postnatal and 3 were undocumented. A
      strategy of bilateral exploration allows for salvage of about 7% of ipsilateral
      testicles and prevent asynchronous torsion in about 4% of neonates. CONCLUSIONS:
      Based on our population, between 8-12% of patients would benefit from bilateral
      exploration at the time of diagnosis. We recommend urgent bilateral exploration
      with orchiopexy of the contralateral testicle in order to avert anorchia. TYPE OF
      STUDY: Systematic review. LEVEL OF EVIDENCE: Level 5 meta-synthesis (Evidence
      from systematic reviews of qualitative and descriptive studies).

PMID- 30098811
TI  - Ten-year reassessment of the shortage of general surgeons: Increases in
      graduation numbers of general surgery residents are insufficient to meet the
      future demand for general surgeons.
AB  - BACKGROUND: In 2008, we projected that a deficit in the general surgical
      workforce would grow to 19% by 2050. We reexamined population-based general
      surgical workforce projections to determine the impact of recent changes in
      population estimates and trends in certification and General Surgery Residency.
      METHODS: We reviewed the Census Bureau data and the potential pool of general
      surgeons defined by American Board of Surgery certificates, residents completing
      Accreditation Council for Graduate Medical Education-approved General Surgery
      Residency and combined American Board of Surgery and osteopathic certificates
      averaged from 2007-2016. The model included removal of 150 surgeons/year who
      subspecialize and 729 retirements/year. RESULTS: Updated census projections
      estimate a 2050 U.S. population of 439 million, a 19 million increase over prior
      census projections. From 2007-2016, the American Board of Surgery granted 10,173
      certificates, averaging 1,017/year; General Surgery Residency graduations were
      10,088, averaging 1,088/year; combined American Board of Surgery and osteopathic
      (American Osteopathic Association) certificates were 10,084, averaging
      1,084/year. General surgical workforce shortage in 2050 is projected to be 7,047
      (21%) based on American Board of Surgery certificates; 4,917(15%) based on
      General Surgery Residency completions; 5,037 (15%) based on combined American
      Board of Surgery and American Osteopathic Association certificates; and 57 (0%)
      based on hypothetical expansion of general surgeons training by 75 positions by
      2021. CONCLUSIONS: Without increasing future general surgeons training numbers,
      the projected future general surgical workforce shortage will continue to grow.

PMID- 30098812
TI  - Opioid prescribing practices during implementation of an enhanced recovery
      program at a tertiary care hospital.
AB  - BACKGROUND: Enhanced recovery programs have demonstrated a decrease in opioid use
      in hospitals where patients have undergone colorectal surgery. This study is to
      investigate whether similar decreases in opioid prescribing are achieved at
      discharge and postdischarge. METHODS: Patients undergoing colorectal surgery
      November 2014-November 2016 were reviewed. Postdischarge opioid prescribing was
      quantified in morphine milligram equivalents at time of discharge, 30 days
      postdischarge, and 60 days postdischarge. Linear regression models were used to
      examine factors predictive of opioid prescribing. RESULTS: A total of 324
      patients treated on enhanced recovery program protocol and 451 patients off
      enhanced recovery program protocol were reviewed. Enhanced recovery program
      patients had shorter lengths of stay: 6.74 +/- 5.3 vs 9.0 +/- 7.0 days (mean +/-
      standard deviation; P < .0001). At discharge, enhanced recovery program patients
      were prescribed higher amounts of opioids (morphine milligram equivalent 307.4 +/
      286.3 vs 242.5 +/- 243.1 [mean +/- SD]; P = .001) and were more likely to
      receive additional opioid prescriptions in the next 30 days (28.7% vs 18.85%; P =
      .0013). Linear regression models suggest that preoperative opioid use, age, and
      treatment on enhanced recovery program protocol were predictive of opioid
      prescribing (morphine milligram equivalent) at time of discharge. CONCLUSION:
      Enhanced recovery program patients received more opioid prescribing (morphine
      milligram equivalent) at discharge and within the first 30 days postdischarge.
      Alternative confounding variables require further investigation.

PMID- 30098813
TI  - Direct oral anticoagulants do not worsen traumatic brain injury after low-level
      falls in the elderly.
AB  - BACKGROUND: Falls are now the leading cause of trauma and represent the most
      common type of trauma in the elderly. The use of anticoagulants is increasing in
      older patients, but there are little data on outcomes after traumatic brain
      injury while anticoagulated with direct oral anticoagulants compared with
      warfarin. We hypothesized that anticoagulated patients would have a greater
      mortality and complications than nonanticoagulated patients, and patients on
      direct oral anticoagulants would have more fatal outcomes after low-level falls
      because of lack of reversal agents. METHODS: Patients 65 years or older admitted
      to level 1-3 trauma centers with 24-hour neurosurgical care were identified
      through the administrative database of 19 Trinity Health hospitals. Patients with
      International Classification of Diseases, Ninth Revision, codes consistent with
      low-level fall and traumatic brain injury from May 2013 through October 2015 were
      included. Preadmission warfarin or direct oral anticoagulant use was extracted
      from admission reconciliation of medications in the database. RESULTS: A total of
      700 patients met inclusion criteria with 177 on anticoagulants before admission.
      Anticoagulated patients had more cardiac (P < .001), pulmonary (P < .001), and
      clotting (P < .02) comorbidities. Warfarin patients had the greatest
      neurosurgical intervention rate at 18% compared with direct oral anticoagulants
      (2.8%, P < .02) or nonanticoagulation (11%, P < .02). No difference was
      identified in overall mortality and mortality after neurosurgical intervention
      between the nonanticoagulated, warfarin, or direct oral anticoagulant groups.
      Warfarin patients received more plasma (P < .001) and red cell transfusions (P =
      .035) with greater intensive care unit stays (P < .001) compared with direct oral
      anticoagulant or nonanticoagulated patients. With logistic regression, only
      advancing age (P < .05) and a lesser Glasgow Coma Scale score (P < .01) were
      associated with greater mortality. CONCLUSION: Older direct oral anticoagulant
      patients with traumatic brain injury after low-level fall did not have increased
      morbidity or mortality compared with those treated with warfarin or who were not
      treated with anticoagulants. Concerns over the use of direct oral anticoagulant
      agents in this population may be overstated and deserve more scrutiny.

PMID- 30098814
TI  - Efficiency of care and cost for common emergency general surgery conditions:
      Comparison by surgeon training and practice.
AB  - BACKGROUND: Our institutional emergency general surgery service is staffed by
      both trauma and critical care-trained surgeons and other boarded general surgeons
      and subspecialists. We compared efficiency of care for common emergency general
      surgery conditions between trauma and critical care-trained surgeons and boarded
      general surgeons and subspecialists. METHODS: Adults admitted between February
      2014 and May 2017 with acute appendicitis, acute cholecystitis, intestinal
      obstruction, incarcerated hernia, or other acute abdominal diagnoses seen by
      emergency general surgery service were included. Demographic characteristics,
      consulting surgeon, operations, outcomes, and cost data were obtained. RESULTS: A
      total of 1,363 patients were included: 384 (28.2%) with acute appendicitis, 477
      (35.0%) with acute cholecystitis, 406 (29.8%) with intestinal obstruction, 22
      (1.6%) with incarcerated hernia, and 74 (5.4%) with other acute abdominal
      diagnoses. Trauma and critical care-trained surgeons saw 836 (61.3%) patients.
      There was no difference in operative management between the two groups, however,
      trauma and critical care-trained surgeons had significantly less time to the
      operative room (7.0 vs 12.9 hours; P < .001), without a difference in duration of
      stay or costs. The subgroups of acute appendicitis and acute cholecystitis when
      treated by trauma and critical care-trained surgeons had less time to the
      operative room (8.4 vs 17.4 hours; P < .001), shorter hospital stay (2.5 vs 2.8
      days; P = .021), and less emergency department cost ($822 vs $876; P = .012).
      CONCLUSION: Compared with boarded general surgeons and subspecialists, trauma and
      critical care-trained surgeons provide more efficient care for common emergency
      general surgery conditions, with less time from consultation to the operative
      room.

PMID- 30098815
TI  - Systematic review and meta-analysis of randomized controlled trials of the
      clinical effectiveness of impervious plastic wound protectors in reducing
      surgical site infections in patients undergoing abdominal surgery.
AB  - BACKGROUND: Surgical site infections are a common postoperative complication
      after abdominal surgery. Although impervious plastic wound protectors have been
      used in surgery to reduce surgical site infection rates, the effectiveness of
      impervious plastic wound protectors for reduction of surgical site infections
      remains unclear. This study aimed to determine the clinical effectiveness of
      impervious plastic wound protectors in reducing surgical site infection rates
      after abdominal surgery. METHODS: A systematic review of the PubMed, Embase, and
      Cochrane Library databases was performed to identify randomized clinical trials
      evaluating surgical site infection risk after abdominal surgeries with and
      without the use of impervious plastic wound protectors. The outcome of interest
      was a well-specified, clinically based definition of surgical site infections. No
      language or time restrictions were applied. The pooled risk ratio was estimated
      with random-effect meta-analysis. The quality assessment of the studies and the
      quantitative analyses were performed in line with the principles of the Cochrane
      Collaboration. RESULTS: Of the 400 studies identified, 14 randomized controlled
      trials representing 2,684 patients were included in this review. The pooled risk
      ratio under a random-effects model was 0.70 (95% confidence interval, 0.51-0.96;
      I2, 56.8%), indicating a potentially significant benefit from impervious plastic
      wound protector use. There was a significant trend toward greater protective
      effect in studies using a dual ring protector (relative risk = 0.31; 95%
      confidence interval, 0.15-0.58), rather than a single ring protector (relative
      risk = 0.84; 95% confidence interval, 0.71-1.00). There was no significant
      between-study heterogeneity or publication bias. CONCLUSION: This study suggests
      that impervious plastic wound protectors are efficient in reducing surgical site
      infection rates in patients undergoing abdominal surgery.

PMID- 30098816
TI  - Re:"Laparoscopic Nissen Fundoplication Controls Symptoms and Improves Disease
      Specific Quality of Life in Patients with Class I and II Obesity".

PMID- 30098817
TI  - [Autosomal-recessive amylosis cutis dyschromica and GPNMB mutations].

PMID- 30098818
TI  - Efficacy and safety data for checkpoint inhibitors in advanced melanoma under
      real-life conditions: A monocentric study conducted in Nice from 2010 to 2016.
AB  - BACKGROUND: Immunotherapies using anti-CTLA4 and anti-PD1 antibodies have
      revolutionised the management of patients with advanced melanoma. The aim of our
      study was to analyse the efficacy and safety of immunotherapies in patients with
      advanced melanoma under real-life conditions. METHODS: We conducted a
      monocentric, retrospective, observational study that included all patients
      treated with immunotherapies (ipilimumab, i.e. ipi; nivolumab, i.e. niv and
      pembrolizumab, i.e. pbr) for advanced melanoma with exclusion of primary mucosal
      or ocular melanoma. The primary endpoint was progression-free survival (PFS).
      RESULTS: A total of 110 patients were included. Median PFS was better in the anti
      PD1 group than in the anti-CTLA4 group (3.9 months vs. 2.9 months, P=0.025). The
      frequency of adverse events of any grade was 53.4% with ipi, 66.7% with niv and
      75% with pbr. DISCUSSION: Our study shows slightly inferior efficacy data vs.
      clinical trials of ipi and niv because patients were presenting more severe
      illness at inclusion. Nevertheless, the study argues in favour of the superiority
      of anti-PD1 antibodies vs. anti-CTLA4 antibodies in terms of PFS and best overall
      response. Moreover, our study exhibits safety data comparable to those from
      clinical trials except for a lower frequency with ipi. CONCLUSION: Our efficacy
      and safety data obtained under real-life conditions are reassuring since they are
      consistent with data already published.

PMID- 30098819
TI  - Effect of Elastic Therapeutic Taping on Abdominal Muscle Endurance in Patients
      With Chronic Nonspecific Low Back Pain: A Randomized, Controlled, Single-Blind,
      Crossover Trial.
AB  - OBJECTIVE: The purpose of this study was to determine the immediate effect of
      elastic therapeutic taping and sham taping of the abdominal musculature on
      maximum hold time of endurance tests in patients with chronic nonspecific low
      back pain (CNLBP). METHODS: Twenty-six people with CNLBP and 26 asymptomatic
      individuals were included in this study. The CNLBP participants were allocated to
      an elastic therapeutic tape group or a sham tape group. Standard adhesive elastic
      therapeutic tape was utilized for facilitatory application in the elastic
      therapeutic tape group. The elastic therapeutic tape group received real elastic
      therapeutic taping on the transversus abdominis and internal obliques, and the
      sham tape group received sham elastic therapeutic taping application. For the
      sham group, the elastic therapeutic tape was positioned horizontally above the
      navel and applied without tension. After a wash-out period, each CNLBP
      participant was switched to the other group. Outcome measures included maximum
      hold time of supine isometric chest raise, supine double straight-leg raise, and
      abdominal drawing in maneuver. RESULTS: The CNLBP participants had lower maximum
      hold time compared to the asymptomatic individuals (P <= .01). Following taping,
      both groups showed an increase in the maximum hold time (mean difference = 4.43 -
      50.69 seconds; P <= .02). Although there was no difference between the results of
      both groups (P >= .12), effect sizes were large for the elastic therapeutic tape
      group (Cohen's d = -1.93 to -1.00). CONCLUSIONS: The results suggest that the
      maximum hold time of endurance tests was decreased in CNLBP patients compared to
      healthy participants. The application of both elastic therapeutic tape and sham
      tape to the transversus abdominis and internal obliques produced short-term
      improvement in abdominal endurance. There was no statistically significant
      difference between the results of elastic therapeutic tape and sham tape.

PMID- 30098821
TI  - Association Between Trapezius Muscle Tenderness and Tension-Type Headache in
      Female Office Workers: A Cross-sectional Study.
AB  - OBJECTIVE: The purpose of the study was to determine the association between
      trapezius muscle tenderness and tension-type headache among female office
      workers. METHODS: Through a questionnaire survey, 256 female office workers with
      tension-type headaches reported the level of palpable tenderness ("no," "some,"
      or "severe tenderness") in the trapezius muscle. The number of days with headache
      ("0-7," "8-14," or ">14"), intensity ("low," "moderate," or "high"), duration of
      headache ("<8 hours per day," ">8 hours per day," and "all day"), and use of
      analgesic medications were reported. Odds ratio (OR) for tenderness in the
      trapezius muscle ("no/some" vs "severe tenderness") as a function of days with
      headache, intensity of headache, duration of headache, and use of analgesic
      medications were calculated using a binary logistic regression controlling for
      age and body mass index. RESULTS: After adjustments for confounders, a strong
      association was found between the level of trapezius muscle tenderness and
      intensity of headache (moderate intensity, OR 2.45; 95% confidence interval [CI]
      1.08-5.54; high intensity, OR 7.51 [95% CI 2.65-21.29]) and days with headache
      (>14 days, OR 4.75 [95% CI 1.41-15.89]). No association was observed for duration
      of headache or use of analgesic medications. CONCLUSIONS: For the participants
      studied, there was a strong association between trapezius muscle tenderness and
      the level of intensity and the number of days with a headache among female office
      workers. No association was seen for duration of headaches or use of analgesic
      medications.

PMID- 30098820
TI  - Prevalence of Work-Related Musculoskeletal Disorders in Iranian Physical
      Therapists: A Cross-sectional Study.
AB  - OBJECTIVE: The purpose of this study was to determine the prevalence of
      musculoskeletal disorders among Iranian physical therapists. METHODS: A cross
      sectional study was carried out. An online survey was completed by Iranian
      physiotherapists from June 2017 to August 2017. A total of 333 online
      questionnaires were sent, and 319 questionnaires were fully completed and used
      for data analysis. The Persian version of the Nordic Questionnaire was the main
      outcome measurement. This questionnaire identified work-related pain or
      discomfort in 9 parts of the body, including: (1) neck, (2) shoulder, (3) elbow,
      (4) wrists, (5) upper back, (6) lumbar, (7) thighs, (8) knee, and (9) ankle.
      RESULTS: The findings of this study showed the prevalence of musculoskeletal
      disorders was 94% in Iranian physiotherapists. Lumbar (65%), neck (57.4%),
      shoulder (50.2%), upper back (49%), and knee (45.5%) were the most prevalent
      regions of these disorders. While ankle (19.7%) and elbow (21.6%) disorders
      showed the lowest prevalence. CONCLUSION: The prevalence of work-related
      musculoskeletal disorders was high in Iranian physiotherapists, especially in the
      lumbar, neck, shoulder, and upper back regions.

PMID- 30098822
TI  - Combined Use of Diadynamic Currents and Manual Therapy on Myofascial Trigger
      Points in Patients With Shoulder Impingement Syndrome: A Randomized Controlled
      Trial.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effect of combined
      manual therapy (MT) and diadynamic (DD) currents on myofascial trigger points of
      the upper trapezius muscle in individuals with a diagnosis of unilateral shoulder
      impingement syndrome. METHODS: A randomized clinical trial was conducted
      involving 60 individuals with shoulder impingement syndrome who were allocated to
      the following 3 groups: (1) MT and DD currents (MTDD), (2) MT alone, and (3) DD
      currents alone. The participants were submitted to 16 treatment sessions over an
      8-week period and were evaluated using the Numerical Rating Pain Scale as well as
      the pain and disability subscales of the Shoulder Pain and Disability Index.
      RESULTS: Differences in Numerical Rating Pain Scale scores (secondary outcome)
      between MTDD and MT groups (mean difference 2.25 points, 95% confidence interval
      1.07-3.42) and between MTDD and DD groups (mean difference 2.30 points, 95%
      confidence interval 1.42-3.17) were clinically relevant. No clinical gains were
      observed in the comparisons between groups of Shoulder Pain and Disability Index
      scores. CONCLUSION: The combination of MT and DD currents on myofascial trigger
      points was more effective at reducing pain intensity but not disability than each
      therapy performed individually for patients with unilateral shoulder impingement
      syndrome.

PMID- 30098823
TI  - Inflammatory juvenile compound nevi: A melanoma is not all that it appears to be.
AB  - An 11 year-old girl presented with a recent growth pigmented conjuntival lesion
      in the bulbar conjunctiva of left eye. Due to the the biomicroscopic and
      ultrasound findings, an excisional biopsy was performed on the lesion using the
      "no touch" technique, as well as cryo-coagulation of surgical margins.
      Histopathological examination revealed an inflammatory compound nevus. Melanotic
      conjunctival tumours are mostly benign. However, the recent growth of a lesion,
      its vascularisation, irregularities of the margins, and colour change must
      suggest it has turned malignant. In such case, excision of the lesion is
      mandatory. Despite all the clinical changes, especially in young patients, it can
      still be an inflammatory compound nevus.

PMID- 30098824
TI  - The practice of ophthalmology in Mexico in the 18th century.

PMID- 30098825
TI  - Multimodal non-invasive imaging in choroidal rupture secondary to a firework
      explosion.

PMID- 30098826
TI  - Utility of temporal profiles of new cardio-renal and pulmonary candidate
      biomarkers in chronic heart failure.
AB  - BACKGROUND: Our aim was to explore potential use of temporal profiles of seven
      emerging cardio-renal and two pulmonary candidate biomarkers for predicting
      future adverse clinical outcome in stable patients with chronic heart failure
      (CHF). METHODS: In 263 CHF patients, we determined the risk of a composite
      endpoint of HF-hospitalization, cardiac death, LVAD-placement and heart
      transplantation in relation to repeatedly assessed (567 samples in total) blood
      biomarker levels, and slopes of their temporal trajectories (i.e., rate of
      biomarker change per year). In each patient, we estimated biomarker trajectories
      using repeatedly measured osteopontin (OPN), osteoprotegerin (OPG), epidermal
      growth factor receptor (EGFR), heparin-binding protein (HBP), trefoil factor-3
      (TFF3), kallikrein-6 (KLK-6), matrix extracellular phosphoglycoprotein (MEPE),
      pulmonary surfactant-associated protein-D (PSP-D), and secretoglobulin family 3A
      member-2 (SCGB3A2). RESULTS: During 2.2 years of follow-up, OPN, OPG, and HBP
      levels predicted the composite endpoint (univariable hazard ratio [95% confidence
      interval] per 1SD increase: 2.31 [1.76-3.15], 2.23 [1.69-3.00], and 1.36[1.09
      1.70]). Independently of the biomarkers' levels, the slopes of OPG, TFF-3, PSP-D
      trajectories were also strong clinical predictors (per 0.1SD increase: 1.24 [1.14
      1.38], 1.31 [1.17-1.49], and 1.32 [1.21-1.47]). All associations persisted after
      multivariable adjustment for baseline characteristics, and repeatedly assessed
      CHF pharmacological treatment and cardiac biomarkers NT-proBNP and troponin T.
      CONCLUSIONS: Repeatedly-measured levels of OPN, OPG, and HBP, and slopes of OPG,
      TFF-3, and PSP-D strongly predict clinical outcome. These candidate biomarkers
      may be clinically relevant as they could further define a patient's risk and
      provide additional pathophysiological insights into CHF.

PMID- 30098828
TI  - High expression of TROP2 is correlated with poor prognosis of oral squamous cell
      carcinoma.
AB  - Human trophoblastic cell-surface antigen 2 (TROP2) is a cell surface glycoprotein
      that exhibits high expression in various carcinomas but low or no expression in
      normal tissues. High TROP2 expression plays an important role in promoting tumor
      development and aggressiveness, which is correlated with reduced patient
      survival. However, there are few studies regarding TROP2 in relation to both oral
      squamous cell carcinoma (OSCC) and oral potentially malignant lesions. The
      expression of TROP2 protein and mRNA was investigated in OSCC tissues, oral
      potentially malignant lesion tissues, and normal oral tissues using
      immunohistochemistry and quantitative real-time polymerase chain reaction (qRT
      PCR). The association between TROP2 expression and clinicopathological
      characteristics of OSCC was also analyzed, and the prognostic value of TROP2 was
      evaluated. The expression of TROP2 protein and mRNA were both higher in OSCC
      tissues than in oral potentially malignant lesion tissues or normal oral tissues.
      Positive TROP2 expression was related to differentiation, lymph node metastases,
      TNM stage, perineural infiltration, and vascular invasion. Poor overall survival
      was associated with high TROP2 expression and other factors associated with poor
      overall survival including poor differentiation, lymph node metastasis, TNM
      stage, vascular invasion, and perineural invasion in univariate analyses. TROP2
      expression as well as TNM stage and vascular invasion were independent prognostic
      factors associated with the overall survival of OSCC patients in multivariate
      analyses. In summary, High TROP2 expression is associated with poor overall
      survival and serves as an independent prognostic factor in OSCC. The results
      suggest that TROP2 expression could be an effective prognostic biomarker for
      OSCC.

PMID- 30098827
TI  - Dose-dependent efficacy of beta-blocker in patients with chronic heart failure
      and atrial fibrillation.
AB  - BACKGROUND: The usefulness of beta-blockers in heart failure (HF) patients with
      permanent atrial fibrillation (AF) has been questioned. METHODS AND RESULTS: We
      analyzed data from HF patients (958 patients (801 males, 84%, age 67 +/- 11
      years)) with AF enrolled in the MECKI score database. We evaluated prognosis
      (composite of cardiovascular death, urgent heart transplant, or left ventricular
      assist device) of patients receiving beta-blockers (n = 777, 81%) vs. those not
      treated with beta-blockers (n = 181, 19%). We also analyzed the role beta1
      selectivity and the role of daily beta-blocker dose. To account for different HF
      severity, Kaplan-Meier survival curves were normalized for relevant confounding
      factors and for treatment strategies. Dose was available in 629 patients. Median
      follow-up was 1312 (577-2304) days in the entire population, 1203 (614-2420) and
      1325 (569-2300) days in patients not receiving and receiving beta-blockers. 224
      (23%, 54/1000 events/year), 163 (21%, 79/1000 events/year), and 61 (34%, 49/1000
      events/year) events were recorded, respectively. At 10-year patients treated with
      beta-blockers had a better outcome (HR 0.447, p < 0.01) with no effects as
      regards beta1selective drugs (53%) vs. beta1-beta2 blockers (47%). Survival
      improved in parallel with beta-blocker dose increase (HR 0.296, 0.496, 0.490 for
      the high, medium, and low dose vs. no beta-blockers, p < 0.0001). CONCLUSION: HF
      patients with AF taking a beta-blocker have a better outcome (with a survival
      improvement in parallel with daily dose but no differences as regards beta1
      selectivity) but this does not mean that beta-blockers improve outcomes in these
      patients as we cannot control for all the potential confounders associated with
      beta-blocker use.

PMID- 30098829
TI  - miR-26b-5p suppresses proliferation and promotes apoptosis in multiple myeloma
      cells by targeting JAG1.
AB  - BACKGROUND: Though the levels of diagnosis and treatment of multiple myeloma (MM)
      have been largely improved recent years, the prognosis of these patients remain
      unacceptable. It is urgent for us to discover the exact mechanism and determine
      some new indicators for MM. MiRNAs play a critical role in the occurrence and
      progression of cancers, including MM. MiR-26b-5p has been reported to be closely
      related to cells proliferation in human pulmonary cancer, hepatocellular
      carcinoma and so on. MATERIAL AND METHODS: Here, we measured the expression of
      miR-26b-5p in MM samples and cell lines by real-time PCR. Then, Kaplan-Meier
      Curves were applied to assess the effect of miR-26b-5p expression on MM patients
      prognosis. Functionally, MTT assay and Flow cytometry were conducted to explore
      the functions of miR-26b-5p in cells proliferation and apoptosis. Furthermore,
      bioinformatics tools, Pearson's correlation coefficient analysis, gain-and loss
      of-function experiments and rescue experiment were used to determine the
      relationship between JAG1 and miR-26b-5p in MM cells. In addition, we also
      confirmed the role of JAG1 in MM cells proliferation and apoptosis by gain-and
      loss of-function experiments. RESULTS: Here, we reported for the first time that
      miR-26b-5p was under-expressed in MM by real-time PCR. Clinically, Kaplan-Meier
      Curves showed that MM patients with lower miR-26b-5p expression had worse
      prognosis. Functionally, MTT assay revealed that miR-26b-5p inhibited cells
      proliferation. Flow cytometry indicated that miR-26b-5p accelerated tumor cells
      apoptosis. Furthermore, bioinformatics tools, Pearson's correlation coefficient
      analysis gain-and loss of-function experiments showed that JAG1 was the target of
      miR-26b-5p in MM cells. And, gain-and loss of-function experiments for JAG1
      confirmed that JAG1 was an oncogene in MM cells. What's more, rescue experiment
      showed that JAG1 mediated the function of miR-26b-5p in MM cells. CONCLUSION: MiR
      26b-5p acts as a tumor suppressor through suppressing cells proliferation and
      inducing cells apoptosis via directly targeting JAG1 in MM. MiR-26b-5p could be a
      potential and ponderable tumor target for MM in future.

PMID- 30098830
TI  - A reply to 'A comment on "Antigenic analysis of genetic variants of Canine
      distemper virus"'.

PMID- 30098831
TI  - The importance of designating type material for uncultured taxa.
AB  - Naming of uncultured Bacteria and Archaea is often inconsistent with the
      International Code of Nomenclature of Prokaryotes. The recent practice of
      proposing names for higher taxa without designation of lower ranks and
      nomenclature types is one of the most important inconsistencies that needs to be
      addressed to avoid nomenclatural instability. The Code requires names of higher
      taxa up to the rank of class to be derived from the type genus name, with a
      proposal pending to formalise this requirement for the rank of phylum.
      Designation of nomenclature types is crucial for providing priority to names and
      ensures their uniqueness and stability. However, only legitimate names proposed
      for axenic cultures can be used for this purpose. Candidatus names reserved for
      taxa lacking cultured representatives may be granted this right if recent
      proposals to use genome sequences as type material are endorsed, thereby allowing
      the Code to be fully applied to lineages represented by metagenome-assembled
      genomes (MAGs) or single amplified genomes (SAGs). Genome quality standards need
      to be considered to ensure unambiguous assignment of type material. Here, we
      illustrate the recommended practice by proposing nomenclature type material for
      four major uncultured prokaryotic lineages based on high-quality MAGs in
      accordance with the Code.

PMID- 30098832
TI  - [Anticoagulation in the elderly: is it all about guidelines or there room for the
      art of medicine?]

PMID- 30098833
TI  - The placebo and its effects: A psychoneuroendocrinological perspective.
AB  - Placebos are usually employed deceptively in clinical trials in order to control
      for non-specific effects. However, since placebos themselves have been found to
      cause clinically relevant changes and in some cases are indistinguishable from
      the verum they are tested against, this theoretically inert, but practically
      effective intervention has become a scientific discipline in its own right. In
      this review, it is argued that placebos are generic and genuine biopsychosocial
      interventions and as such are highly interesting candidates for a
      psychoneuroendocrinological perspective. Yet, despite a considerable conceptual
      proximity between explanatory models of placebos and their effects with
      psychoneuroendocrine models and findings, placebos have thus far not been subject
      to systematic psychoneuroendocrine examination. Consequently, it would be highly
      interesting and informative to make placebos the target of psychoneuroendocrine
      scrutiny.

PMID- 30098834
TI  - Heparin or Sodium Chloride for Prolonging Peripheral Intravenous Catheter Use in
      Children - A Systematic Review.
AB  - PROBLEM: Children's wellbeing should always be considered but during hospital
      stay, many children experience pain due to medical procedures such as inserting a
      peripheral venous catheter. In order to prolong the time in situ and to avoid the
      necessity to change the catheter frequently, it can be flushed with either
      heparin or sodium chloride. Since heparin has negative side effects, the aim of
      this study was to examine whether or not there is any scientific support for
      intermittent flush with heparin being more efficient in extending the time in
      situ as compared to intermittent flush with sodium chloride. ELIGIBILITY
      CRITERIA: A systematic review structured according to PICO was performed. The
      databases used were PubMed, CINAHL and Cochrane Library, and eligible study
      designs were systematic reviews and randomized controlled double-blinded trials.
      The studies were critically appraised and synthesized, after which an evidence
      grading was performed. SAMPLE: Two systematic reviews and four randomized
      controlled double-blinded trials were included. RESULTS: The systematic reviews
      were assessed as high quality and the randomized controlled double-blinded trials
      assessed as moderate quality. The results showed both significant differences,
      and no significant differences between heparin groups and sodium chloride groups
      regarding time in situ. CONCLUSIONS: Our conclusion is that heparin might not be
      necessary but no guidelines are possible to develop. IMPLICATIONS: Since heparin
      has negative side effects among children and no significant result in favor of
      heparin was found, more studies are needed in order to provide evidence-based
      care.

PMID- 30098835
TI  - Generalized anxiety disorder among emergency department patients.

PMID- 30098836
TI  - Platelet indices may not be associated with diagnosis and prognosis of
      gastrointestinal bleeding.

PMID- 30098837
TI  - Preparation of lifeguards to Basic Life Support in the drowning.

PMID- 30098838
TI  - Lycopene treatment inhibits activation of Jak1/Stat3 and Wnt/beta-catenin
      signaling and attenuates hyperproliferation in gastric epithelial cells.
AB  - Helicobacter pylori (H pylori) colonizes the human stomach and increases the risk
      of gastric diseases including gastric cancer. H pylori increases reactive oxygen
      species (ROS), which activate Janus-activator kinase 1 (Jak1)/signal transducers
      and activators of transcription 3 (Stat3) in gastric epithelial cells. ROS
      mediate hyperproliferation, a hallmark of carcinogenesis, by activating Wnt/beta
      catenin signaling in various cells. Lycopene is a potent antioxidant exhibiting
      anticancer effects. We hypothesized that lycopene may inhibit H pylori-induced
      hyperproliferation by suppressing ROS-mediated activation of Jak1/Stat3 and
      Wnt/beta-catenin signaling, and beta-catenin target gene expression in gastric
      epithelial cells. We determined cell viability, ROS levels, and the protein
      levels of phospho- and total Jak1/Stat3, Wnt/beta-catenin signaling molecules,
      Wnt-1, lipoprotein-related protein 5, and beta-catenin target oncogenes (c-Myc
      and cyclin E) in H pylori-infected gastric epithelial AGS cells. The Jak1/Stat3
      inhibitor AG490 served as the control treatment. The significance of the
      differences among groups was calculated using the 1-way analysis of variance
      followed by Newman-Keuls post hoc tests. The results show that lycopene reduced
      ROS levels and inhibited Jak1/Stat3 activation, alteration of Wnt/beta-catenin
      multiprotein complex molecules, expression of c-Myc and cyclin E, and cell
      proliferation in H pylori-infected AGS cells. AG490 similarly inhibited H pylori
      induced cell proliferation, alteration of Wnt/beta-catenin multiprotein complex
      molecules, and oncogene expression. H pylori increased the levels of Wnt-1 and
      its receptor lipoprotein-related protein 5; this increase was inhibited by either
      lycopene or AG490 in AGS cells. In conclusion, lycopene inhibits ROS-mediated
      activation of Jak1/Stat3 and Wnt/beta-catenin signaling and, thus, oncogene
      expression in relation to hyperproliferation in H pylori-infected gastric
      epithelial cells. Lycopene might be a potential and promising nutrient for
      preventing H pylori-associated gastric diseases including gastric cancer.

PMID- 30098839
TI  - Spatial information is preferentially processed by the distal part of CA3:
      Implication for memory retrieval.
AB  - For the past decades, CA3 was considered as a single functional entity. However,
      strong differences between the proximal (close to the dentate gyrus) and the
      distal (close to CA2) parts of CA3 in terms of connectivity patterns, gene
      expression and electrophysiological properties suggest that it is not the case.
      We recently showed that proximal CA3 (together with distal CA1) preferentially
      deals with non-spatial information [1]. In contrast to proximal CA3, distal CA3
      mainly receives and predominantly projects to spatially tuned areas. Here, we
      tested if distal CA3 preferentially processes spatial information, which would
      suggest a segregation of the spatial information along the proximodistal axis of
      CA3. We used a high-resolution imaging technique based on the detection of the
      expression of the immediate-early gene Arc, commonly used to map activity in the
      medial temporal lobe. We showed that distal CA3 is strongly recruited in a newly
      designed delayed nonmatching-to-location task with high memory demands in rats,
      while proximal CA3 is not. These results indicate a functional segregation of CA3
      that mirrors the one reported in CA1, and suggest the existence of a distal CA3-
      proximal CA1 spatial subnetwork. These findings bring further evidence for the
      existence of 'specialized' spatial and non-spatial subnetworks segregated along
      the proximodistal axis of the hippocampus and put forward the 'segregated' view
      of information processing in the hippocampus as a reasonable alternative to the
      well-accepted 'integrated' view, according to which spatial and non-spatial
      information are systematically integrated in the hippocampus to form episodic
      memory.

PMID- 30098840
TI  - Direct infiltration of botulinum toxin into the pterygoid lateral muscle for
      repositioning of the disc during arthroscopy of the temporomandibular joint.

PMID- 30098841
TI  - Burden of Tuberculosis Hospitalizations in Portugal From 2000 to 2015.

PMID- 30098842
TI  - Systemic-to-Pulmonary Artery Fistula as a Late Complication of Biliary Surgery.

PMID- 30098843
TI  - Isolated Myopathy: An Unusual Manifestation of Inhaled Fluticasone Propionate and
      Ritonavir Interaction.

PMID- 30098844
TI  - Avoid valproate in patients with IARS2 mutation.

PMID- 30098845
TI  - Vaginal estrogen: Underprescribed treatment for an underdiagnosed condition of
      menopausal women.

PMID- 30098846
TI  - Effects of cold atmospheric plasma (CAP) on bacteria and mucosa of the upper
      aerodigestive tract.
AB  - OBJECTIVE: Ear, nose and throat infections are among the most common reasons for
      absence from work. They are usually caused by various bacteria like Haemophilus
      influenzae, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus
      pyogenes. Cold atmospheric plasma (CAP) can effectively eliminate even multi
      resistant bacteria and has no cytotoxic or mutagenic effects on the mucosa when
      applied for less than 60s. Aim of the study was to evaluate the effects of CAP on
      common ENT bacteria and on the mucosa of the upper aerodigestive tract. METHODS:
      The bactericidal effects of CAP against the bacteria most commonly causing ENT
      infections were investigated using the colony-forming units assay (CFU) on a
      Muller-Hinton agar plate after applying CAP for 30, 60, 90 and 120s. To evaluate
      the interaction of CAP with mucosal cells, 3D mini organ cultures were treated
      for up to 180s, after which cell viability and necrosis induction were evaluated.
      RESULTS: Treatment with CAP for 60s or longer induced at least a 3-log10
      reduction in the bacterial load (> 99.9%). Treatment times shorter than 60s had
      only slight cytotoxic effects on cell viability and necrosis whereas treatment
      times above 60s showed a fast increase of cytotoxic side effects. CONCLUSION: CAP
      exhibited strong bactericidal effects on the most common ENT pathogens. Treatment
      times of up to 60s showed only minimal adverse reactions in healthy mucosa. CAP
      could be a promising new therapeutic modality for ENT infections.

PMID- 30098847
TI  - Meta-analysis of the efficacy and safety of structured triglyceride lipid
      emulsions in parenteral nutrition therapy in China.
AB  - BACKGROUND & AIMS: We performed a meta-analysis of data from recent studies to
      evaluate the safety and efficacy of parenteral nutrition (PN) with structured
      triglyceride (STG) lipid emulsions compared to medium-chain triglyceride
      (MCT)/long-chain triglyceride (LCT) lipid emulsions in Chinese patients. METHODS:
      PubMed, Embase, Cochrane Library, China National Knowledge Internet, Wanfang, and
      VIP were searched for randomized controlled trials comparing STGs with MCTs/LCTs
      published in English or Chinese between January 1987 and October 2017. Two
      independent investigators screened and selected studies according to prespecified
      selection criteria. Data were pooled and analysed using RevMan(r) version 5.3.
      RESULTS: Thirty-two studies comprising 1944 patients were included in the meta
      analysis. Compared with MCT/LCT emulsions, STGs resulted in a shorter hospital
      length of stay (LOS) (weighted mean difference [WMD], -1.65 days; 95% confidence
      interval [CI]: -2.63, -0.67; P = 0.001) and lower adverse event rates (relative
      risk, 0.64; 95% CI: 0.48, 0.85; P = 0.002). STGs were associated with a
      significantly better cumulative nitrogen balance (WMD, 4.04 g/24 h; 95% CI: 3.10,
      4.97; P < 0.0001) as well as higher concentrations of pre-albumin (WMD 35.20
      mg/L; 95% CI: 26.59, 43.81; P < 0.0001) and albumin (WMD, 1.64 g/L; 95% CI: 1.17,
      2.10; P < 0.0001) compared with MCTs/LCTs. In contrast, significantly lower
      concentrations of plasma triglycerides (WMD, -0.21 mmol/L; 95% CI: -0.30, -0.12;
      P < 0.0001), total cholesterol (WMD, -0.45 mmol/L; 95% CI: -0.60, -0.29; P <
      0.0001), alanine aminotransferase (WMD, -7.68 IU/L; 95% CI: -9.68, -5.68; P <
      0.0001) and aspartate aminotransferase (WMD, -10.27 IU/L; 95% CI: -16.05, -4.49;
      P = 0.0005) were observed in patients receiving STGs compared with MCT/LCTs. STGs
      were also associated with reduced inflammation and improved immunological
      function, as reflected by significantly lower C-reactive protein concentrations
      (WMD, -2.67 mg/L; 95% CI: -4.55, -0.79; P = 0.005) and increased concentrations
      of IgG (WMD, 2.11 g/L; 95% CI: 0.23, 3.99; P = 0.03), IgA (WMD, 0.21 g/L; 95% CI:
      0.14, 0.28; P < 0.0001), CD3+ (WMD, 5.81%; 95% CI: 0.92, 10.70; P = 0.02), and
      CD4+/CD8+ (WMD, 0.12; 95% CI: 0.00, 0.24; P = 0.04) compared with MCT/LCTs.
      CONCLUSIONS: Administration of STGs was shown to improve hepatic function,
      nutrition status, and immunological function and reduce inflammation, LOS, and
      adverse events compared with MCT/LCTs in Chinese patients receiving PN.

PMID- 30098849
TI  - Performance of Candida albicans germ tube antibodies (CAGTA) and its association
      with (1 -> 3)-beta-D-glucan (BDG) for diagnosis of invasive candidiasis (IC).

PMID- 30098850
TI  - Carry-over of host nutrients during sampling enhances undesired growth of
      Staphylococcus aureus in liquid Amies transport medium.
AB  - Optimal transportation of bacteria is important for accurate clinical
      interpretation, quantitative assays, and microbiome studies. A transport medium
      should ideally keep the bacteria alive without supporting growth or altering the
      relative proportions of the constituent species. We investigated the effect of
      nasal mucus and mucin on the growth and survival of two Staphylococcus aureus
      strains in liquid Amies transport medium at room temperature and 4  degrees C for
      14 days. The study showed that the presence of nasal mucus in microbiological
      samples stimulated undesired S. aureus growth at room temperature in a dose
      dependent manner. These findings underscore that microbiological samples from
      humans and animals should be stored at 4  degrees C until analysis to avoid
      undesired S. aureus growth.

PMID- 30098851
TI  - Outpatient parenteral antimicrobial therapy (OPAT) in the UK: a cross-sectional
      survey of acute hospital trusts and health boards.
AB  - This study reviews the current OPAT service provision in the UK and evaluates
      concordance with the national OPAT practice guidelines (standards of care). We
      conducted a survey of acute hospital trusts and health boards in the UK regarding
      OPAT practices between June and September 2017. 165 (93%) of the 178 acute
      hospital trusts/health boards that were contacted responded to the survey. 100
      (61%) indicated they had an OPAT service. Ten (10%) OPAT services did not involve
      an infection specialist. Bone and joint infections, and skin and soft-tissue
      infections were the most common conditions treated. Most OPAT services (74%) hold
      weekly multidisciplinary meetings/virtual ward rounds to review patient's
      progress. 73% had a dedicated OPAT database. We identified variations in practice
      and concordance with the national OPAT good practice guidelines. In an era of
      increasing demand for home-based care, further studies are required to identify
      the optimal configuration of OPAT services with regards to quality and patient
      safety.

PMID- 30098848
TI  - ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Home
      parenteral nutrition.

PMID- 30098852
TI  - Effect of increasing meropenem MIC on the killing activity of meropenem in
      combination with amikacin or polymyxin B against MBL- and KPC-producing
      Enterobacter cloacae.
AB  - Carbapenem resistant Enterobacteriaceae (CRE) are a growing threat worldwide.
      Infections caused by these organisms have exhibited high rates of mortality (50%)
      for which there is no standard of care and a dearth of clinical trials. Most in
      vitro data on CRE focus on Klebsiella pneumoniae, but it is known that effective
      therapy may depend on species or even strain. To address this, meropenem,
      amikacin, and polymyxin B alone and in combination were evaluated by time kill
      against four carbapenem-producing Enterobacter cloacae clinical isolates
      representing a range of meropenem nonsusceptibility (2-32 mg/L) and resistance
      mechanisms (KPC 2 and/or VIM 1). As meropenem minimum inhibitory concentration
      (MIC) increased, bactericidal activity and synergy were maintained for 48 hours
      in isolates exposed to meropenem and amikacin, but synergy and bactericidal
      activity were not maintained in all isolates exposed to meropenem and polymyxin
      B.

PMID- 30098853
TI  - Cognitive control network dysconnectivity and response to antipsychotic treatment
      in schizophrenia.
AB  - To better understand cognitive control impairment in schizophrenia, it is vital
      to determine the extent of dysfunctional connectivity in the associated fronto
      striatal brain network, with a focus on the connections with the anterior
      cingulate cortex (ACC), prior to the potential confounding effect of medication.
      It is also essential to determine the effects following antipsychotic medication
      and the relationship of those effects on psychosis improvement. Twenty-two
      patients with schizophrenia, initially unmedicated and after a 6-week course of
      risperidone, and 20 matched healthy controls (HC) performed a fMRI task twice,
      six weeks apart. We investigated group and longitudinal differences in ACC
      related functional connectivity during performance of a Stroop color task as well
      as connectivity patterns associated with improvement in psychosis symptoms.
      Unmedicated patients with schizophrenia showed greater functional connectivity
      between ACC and bilateral caudate and midbrain and lower connectivity with left
      putamen compared to healthy controls. At baseline, greater functional
      connectivity between ACC and bilateral putamen predicted subsequent better
      treatment response. Change in functional connectivity between ACC and left
      putamen positively correlated with better treatment response. These results
      suggest that patterns of functional connectivity in fronto-striatal networks can
      be utilized to predict potential response to antipsychotic medication. Prior to
      treatment, brain function may be structured with a predisposition that favors or
      not treatment response.

PMID- 30098854
TI  - Relationship between pneumonia and cardiovascular diseases: A retrospective
      cohort study of the general population.
AB  - AIMS: To evaluate the relationship between cardiovascular diseases (CVDs) and
      pneumonia in the general population. METHODS: This retrospective observational
      study included two cohorts, namely CVD (n = 28,363) and non-CVD (n = 28,363)
      cohorts, which were matched by propensity score and examined for cases of
      pneumonia. Data were obtained from 2000 to 2011. In both cohorts, pneumonia risk
      was measured using multivariable Cox proportional hazard models. RESULTS: With
      the non-CVD cohort as reference, the corresponding adjusted hazard ratios (aHRs)
      [95% confidence intervals (CIs)] of pneumonia were 2.03 [1.77-2.31] for coronary
      artery disease, 4.11 [3.15-5.36] for heart failure, 3.21 [2.70-3.81] for
      cerebrovascular disease, 1.46 [1.07-1.98] for peripheral vascular disease, and
      2.27 [2.01-2.56] for the CVD cohort. The cohort with comorbidities had a higher
      risk (all p < .05) of pneumonia compared with that without comorbidities, except
      for patients with the comorbidities of hypertension, hyperlipidemia, obesity, and
      liver disease. The aHR (95% CI) of pneumonia for antibiotic use was 1.26 (1.09
      1.47). The aHRs of community-acquired pneumonia (CAP) and hospital-acquired
      pneumonia (HAP) were 3.25 (95% CI = 1.04-10.1) and 2.95 (95% CI = 2.25-3.88),
      respectively. The aHRs (95% CI) were 1.78 (1.05-3.03) for intensive care unit
      (ICU) risk and 0.98 (0.96-0.99) for length of admission. CONCLUSION: Pneumonia
      risk was associated with CVDs, especially heart failure, regardless of age,
      gender, comorbidities, and antibiotic use, particularly in elderly male patients.
      In addition, Patients with CVDs had a higher risk of CAP and HAP. The CVD cohort
      had a higher frequency of ICU admissions, but shorter admission lengths.

PMID- 30098855
TI  - Association between ankylosing spondylitis and chronic obstructive pulmonary
      disease in Taiwan.

PMID- 30098857
TI  - Scientific Biography of a Mid-Career Physician-Scientist: Getting by With Help
      From My Friends.

PMID- 30098856
TI  - Recovery of dehydrated aerobic granules: A comparison.
AB  - Dehydrated aerobic granules, if can be sufficiently recovered without significant
      loss of structural stability and biological activities, presents a promising long
      time storage option in practical use. This study dehydrated aerobic granules by
      six protocols: air drying at 25 or 50  degrees C, freeze-dry, acetone or ethanol
      dehydration, and microwave heating, and then recovered them in liquid medium,
      with the measured characteristics being reported. The granule stability has no
      correlation with measured settleability, hydrophobicity or extracellular
      polymeric substances compositions; instead, is correlated with the functional
      strains presented in the recovered granules. Air dry dehydration minimally damage
      the functional strains including genus Brevundimonas and genus Comamonas and
      markedly deteriorated structural breaker such as Acinetobacter of Moraxellaceae
      to lead to stable and tough recovered granules.

PMID- 30098858
TI  - Letter re: Comparison of acetabular and femoral morphologies on hip, pelvic, and
      lumbar radiographs (Yun et al.).

PMID- 30098859
TI  - The Association of Serum Carotenoids, Tocopherols, and Ascorbic Acid With Rapid
      Kidney Function Decline: The Coronary Artery Risk Development in Young Adults
      (CARDIA) Study.
AB  - OBJECTIVE: Nutritional intervention targeting dietary intake modification is a
      major component of treatment for chronic kidney disease; however, little is known
      about the relationship between dietary intake and kidney function decline in
      individuals with preserved kidney function. DESIGN AND METHODS: In this
      prospective cohort study we examined the association of biomarkers of dietary
      intake with kidney function decline over a 5-year interval in 2,152 men and women
      with cystatin-C-based estimated glomerular filtration rate > 60 mL/minute/1.73 m2
      from the Coronary Artery Risk Development in Young Adults study. The biomarkers
      of interest included carotenoids, tocopherols, and ascorbic acid. Multivariable
      logistic regression was used to explore the relationship between serum
      concentrations of the sum of 4 carotenoids (alpha-carotene, beta-carotene, beta
      cryptoxanthin, and lutein/zeaxanthin), lycopene, alpha-tocopherol, gamma
      tocopherol, and ascorbic acid and rapid kidney function decline, defined as .15%
      decline in cystatin-C-based estimated glomerular filtration rate over 5 years.
      RESULTS: During the 5-year follow-up, 290 participants (13.5%) experienced rapid
      kidney function decline. Relative to individuals in the lowest quartile of serum
      carotenoids, those in the highest quartile had significantly lower odds of rapid
      kidney function decline in the fully adjusted model (odds ratio, 0.51; 95%
      confidence interval [CI], 0.32-0.80; P trend, .02). No association of levels of
      serum tocopherols, ascorbic acid, or lycopene with kidney function decline was
      found. There was no evidence that results differed for individuals with
      hypertension or diabetes. CONCLUSIONS: These results demonstrate that higher
      serum carotenoid levels, reflective of a fruit- and vegetable-rich dietary
      pattern, inversely associate with rapid kidney function decline in early middle
      adulthood and provide insight into how diet might play a role in chronic kidney
      disease prevention.

PMID- 30098860
TI  - Comparison of DEXA and Bioimpedance for Body Composition Measurements in
      Nondialysis Patients With CKD.
AB  - OBJECTIVES: The aims of this study are (1) to compare dual-energy X-ray
      absorptiometry (DEXA) and bioimpedance for body composition measurements in
      nondialysis patients with chronic kidney disease, and (2) to investigate factors
      associated with any measurement differences. DESIGN AND METHODS: This is a
      substudy using some baseline data from a randomized controlled clinical trial.
      One hundred twenty patients (aged 65 +/- 14 years) with a measured glomerular
      filtration rate 8 to 55 mL/min/1.73m2, not on renal replacement therapy,
      irrespective of age and number of comorbidities, were included from 2011 to 2016.
      For DEXA measurements, Lunar Prodigy or Lunar iDXA were used. For bioimpedance
      measurements, body composition monitor (BCM) was used. Glomerular filtration rate
      was measured with iohexol clearance. Data were analyzed using R software. Bland
      Altman analysis was performed to compare the 2 measurements. The measurement
      difference was DEXA minus BCM. Multiple linear regression analysis was performed
      to analyze relationships between variables. RESULTS: The estimation of fat-free
      mass was higher using BCM than DEXA, with a mean difference of -2.8 kg and limits
      of agreement (mean +/- 2 SD) ranging from -12 kg to 6.5 kg. The estimation of fat
      mass was lower using BCM than DEXA, with a mean difference of 3.1 kg and limits
      of agreement (mean +/- 2 SD) ranging from -6.8 kg to 13 kg. The measurement
      differences were significantly related to lean tissue index, fat tissue index,
      extracellular water, intracellular water, extracellular water/intracellular
      water, total body water, and overhydration. CONCLUSION: Our study showed a
      limited agreement between DEXA and bioimpedance, indicating that these 2
      measurements are not interchangeable in nondialysis patients with chronic kidney
      disease. Lean tissue index, fat tissue index, and body water might contribute to
      the measurement differences, while measured glomerular filtration rate is not a
      factor associated with the measurement differences for body composition. Thus, we
      suggest that the same measure of body composition be used over time.

PMID- 30098861
TI  - The Effect of Inhaled Milrinone Versus Inhaled Levosimendan in Pulmonary
      Hypertension Patients Undergoing Mitral Valve Surgery - A Pilot Randomized Double
      Blind Study.
AB  - OBJECTIVE: To compare the effects of inhaled milrinone and levosimendan on
      pulmonary and systemic hemodynamics in patients with pulmonary hypertension.
      DESIGN: Prospective, double-blind, randomized controlled study. SETTING: Tertiary
      care cardiac institute with 650 beds. PARTICIPANTS: The study comprised 150 adult
      patients with pulmonary hypertension undergoing mitral valve surgery.
      INTERVENTIONS: Patients were assigned randomly into 1 of the following 3 groups:
      milrinone (M), levosimendan (L), or control (C); n = 50 per group. In group M,
      inhaled milrinone (50 ug/kg); in group L, inhaled levosimendan (24 ug/kg); and in
      group C, normal saline was administered when the patient arrived in the recovery
      room. Pre-inhalation and post-inhalation hemodynamics (mean arterial pressure
      [MAP], pulse rate, and systemic vascular resistance [SVR]) were noted until 24
      hours of inhalation of the drug. The change in pulmonary artery pressures
      (pulmonary artery systolic pressure [PASP] and mean pulmonary artery pressure
      [MPAP]) and the duration for which they remained decreased compared with the
      control group, were noted. MEASUREMENTS AND MAIN RESULTS: MAP, pulse rate, and
      SVR were comparable in the 3 groups at various time intervals. PASP and MPAP
      decreased comparably after inhalation of levosimendan and milrinone. However,
      they reached levels near the control group values after 2.5 to 3 hours in group L
      and after 0.5 hours in group M. CONCLUSIONS: Because inhaled levosimendan causes
      a decrease in PASP and MPAP without causing a decrease in SVR and MAP, the
      authors conclude that inhaled levosimendan is a selective pulmonary vasodilator.
      It is as effective as milrinone in reducing pulmonary artery pressures. In
      addition, it has advantage over inhaled milrinone because it is has a longer
      duration of action.

PMID- 30098862
TI  - Clinical Efficacy of Spectral Computed Tomography for Evaluating Liver Function
      in Patients with Budd-Chiari Syndrome.
AB  - RATIONALE AND OBJECTIVES: To analyze the clinical relevance of quantitative
      spectral parameters in evaluating the treatment of patients with Budd-Chiari
      syndrome (BCS) with different classes of liver function by comparing normalized
      iodine concentration (NIC) before and after BCS treatment. MATERIALS AND METHODS:
      Angiographic data were obtained from 41 patients with confirmed BCS between
      December 2015 and March 2017. All patients underwent spectral computed tomography
      (CT) before and after BCS treatment; the average interval between scans was 2-4
      months. Iodine concentration and NIC were measured and calculated during the
      portal venous phase in liver segments I-VIII. Clinical liver function parameters
      including prothrombin time (PT), albumin (ALB), total bilirubin (TBIL), aspartate
      aminotransferase, and alanine aminotransferase were recorded. Liver function was
      classified according to the Child-Pugh grading standard (before treatment). Liver
      NIC and liver function-related parameters before and after treatment were
      compared using the paired t-test; Pearson correlation analysis was performed to
      analyze the aforementioned parameters among different liver function classes
      before BCS treatment. p < 0.05 was to be statistically considered significant.
      RESULTS: PT and TBIL were negatively correlated with liver NIC (p < 0.05),
      whereas ALB and liver NIC exhibited a positive correlation (p < 0.05). Comparison
      of NIC before and after treatment revealed that NIC in liver segments I-VIII was
      higher after treatment. The p values for segments II-VIII were 0.041, 0.046,
      0.041, 0.038, 0.039, 0.042, and 0.040, respectively; the differences were
      statistically significant (p < 0.05). The increase in NIC in liver segments I
      VIII before and after treatment was more significant in patients with class C
      liver function than in their class B and A counterparts. Comparison of liver
      function-related parameters revealed that PT was shortened after treatment; ALB
      levels were increased; and TBIL, alanine aminotransferase, and aspartate
      aminotransferase levels were decreased. CONCLUSION: NIC determined through
      spectral CT was beneficial for evaluating liver function in patients with BCS,
      and can provide imaging data for reexamination, prognostic evaluation, and follow
      up of patients with BCS after treatment. Liver parenchyma NIC values in BCS
      patients with varying liver function may provide a degree of diagnostic value.
      Multi-locus and multi-parameter studies of spectral CT can help to further
      evaluate liver function and assess prognosis in patients with BCS.

PMID- 30098864
TI  - Cutaneous permeability barrier function in signal transducer and activator of
      transcription 6-deficient mice is superior to that in wild-type mice.
AB  - BACKGROUND: Th2 cytokines exhibit a variety of inhibitory effects on permeability
      barrier function via signal transducer and activator of transcription 6 (STAT6).
      However, the role of STAT6 signaling on the construction and/or homeostasis of
      permeability barrier function in the physiological state has not been fully
      assessed. OBJECTIVE: We compared permeability barrier function between Stat6
      deficient and wild-type C57BL/6 mice at steady state. METHODS AND RESULTS:
      Measurement of transepidermal water loss and quantitative penetration assay
      revealed that permeability barrier function was superior in Stat6-deficient mice.
      Accordingly, expressions of loricrin, acidic sphingomyelinase (aSMase) and beta
      glucocerebrosidase (beta-GlcCer'ase) in epidermis and ceramide levels in stratum
      corneum were elevated in STAT6-deficient mice. On the other hands, up-regulations
      of loricrin, aSMase and beta-GlcCer'ase were not observed in 3-dimensionally
      cultured human keratinocytes transfected with siRNA for STAT6. Meanwhile, number
      of mast cells in the dermis was decreased in Stat6-deficient mice. CONCLUSIONS:
      These results suggest that STAT6 signaling negatively affects permeability
      barrier function in vivo, even in the physiological state. However, the superior
      permeability barrier function in Stat6-deficient mice may be a secondary effect
      exerted via cells other than keratinocytes, such as mast cells, since mast cells
      are known to influence permeability barrier function in vivo. Blockade of STAT6
      signaling might be a strategy to augment the permeability barrier function.

PMID- 30098865
TI  - Identification of a novel series of potent and selective CCR6 inhibitors as
      biological probes.
AB  - CCR6 has been implicated in both autoimmune diseases and non-autoimmune diseases.
      Thus, inhibition of CCR6-dependent cell migration is an attractive strategy for
      their treatment. An orally available small molecule inhibitor of CCR6 could
      therefore be a useful biological probe for the pathophysiological studies.
      Initial SAR study of a hit compound provided potent N-benzenesulfonylpiperidine
      derivatives that suppressed CCL20-induced Gi signals. By subsequent scaffold
      morphing of the central ring and further optimization, we identified a novel
      series of 1,4-trans-1-benzenesulfonyl-4-aminocyclohexanes as potent and selective
      CCR6 inhibitors with good pharmacokinetic properties. Our compounds showed good
      correlation between Gi signal inhibitory activity and cell migration inhibitory
      activity in human CCR6-transfected CHO cells. In addition, representative
      compound 35 potently inhibited CCR6-dependent cell migration and the increase in
      ERK phosphorylation in human primary cells. Therefore, the compound could be used
      effectively as a biological probe against human CCR6.

PMID- 30098863
TI  - HIF-1alpha-induced xenobiotic transporters promote Th17 responses in Crohn's
      disease.
AB  - In Crohn's disease, pathogenic Th17-cells express low levels of CD39
      ectonucleotidase and are refractory to the immunosuppressive effects of
      unconjugated bilirubin (UCB), an endogenous ligand for aryl-hydrocarbon-receptor
      (AhR). This resistance to AhR ligation might be associated with alterations in
      responses to hypoxia. Limited exposure to hypoxia appears beneficial in acute
      tissue injury. However, in protracted inflammation, hypoxemia may paradoxically
      result in Th17-cell activation. We report here that in vitro exposure of Th17
      cells from Crohn's disease patients to hypoxia limits responsiveness to AhR
      stimulation by UCB, as reflected by lower CD39 levels. Blockade of hypoxia
      inducible-factor-1alpha (HIF-1alpha) upregulates CD39 and favors Th17-cell
      regulatory responses. Resistance of Th17-cells to AhR signaling results, in part,
      from HIF-1alpha-dependent induction of ATP-binding cassette (ABC) transporters:
      multidrug-resistance-protein-1 (MDR1) and multidrug-resistance-associated-protein
      4 (MRP4). Increased ABC transporters promote efflux of suppressive AhR ligands,
      such as UCB, from Th17-cells. Inhibition of MDR1, MRP4 and/or HIF-1alpha with
      ritonavir (RTV) reconstitutes AhR function in Th17-cells, enhancing therapeutic
      effects of UCB in dextran-sulfate-sodium-induced experimental colitis.
      Deleterious effects of hypoxia on Th17-cells in Crohn's disease can be
      ameliorated either by inhibiting HIF-1alpha or by suppressing ABC transporters to
      increase UCB availability as an AhR substrate. Targeting HIF-1alpha-ABC
      transporters could provide innovative therapeutic pathways for IBD.

PMID- 30098867
TI  - Inhibition of the LOX enzyme family members with old and new ligands. Selectivity
      analysis revisited.
AB  - Lysyl oxidase (LOX) enzymes as potential drug targets maintain constant attention
      in the therapy of fibrosis, cancer and metastasis. In order to measure the
      inhibitory activity of small molecules on the LOX enzyme family members a
      fluorometric activity screening method was developed. During assay validation,
      previously reported non-selective small inhibitor molecules (BAPN, MCP-1, thiram,
      disulfiram) were investigated on all of the major LOX enzymes. We confirmed that
      MCP-1, thiram, disulfiram are in fact pan-inhibitors, while BAPN inhibits only
      LOX-like enzymes (preferably LOX-like-protein-2, LOXL2) in contrast to the
      previous reports. We measured the LOX inhibitory profile of a small targeted
      library generated by 2D ligand-based chemoinformatics methods. Ten hits (10.4%
      hit rate) were identified, and the compounds showed distinct activity profiles.
      Potential inhibitors were also identified for LOX-like-protein-3 (LOXL3) and LOX
      like-protein-4 (LOXL4), that are considered as emerging drug targets in the
      therapy of melanoma and gastric cancer.

PMID- 30098866
TI  - Novel, potent, selective and brain penetrant vasopressin 1b receptor antagonists.
AB  - Herein we report the discovery of a novel oxindole-based series of vasopressin 1b
      (V1b) receptor antagonists. Introducing a substituted piperazine moiety and
      optimizing the southern and the northern aromatic rings resulted in potent,
      selective and brain penetrant V1b receptor antagonists. Compound 9c was found to
      be efficacious in a rat model of anti-depressant activity (3 mg/kg, ip).
      Interestingly, both moderate terminal half-life and moderate bioavailability
      could be achieved despite sub-optimal microsomal stability.

PMID- 30098868
TI  - Monoterpene's multiple free radical scavenging capacity as compared with the
      radioprotective agent cysteamine and amifostine.
AB  - Monoterpenes are major active components of lavender, thyme, and mint. The X-ray
      radioprotective activity of pure monoterpenes is attributed to their scavenging
      ability against active species, but so far no firm evidence has been
      demonstrated. The objective of this study is to quantitatively determine
      antioxidant abilities of monoterpenes and collate it with radioprotective
      activity. Using multiple free-radical scavenging (MULTIS) method, we have
      determined the scavenging abilities of monoterpenes (linalool, thymol, and
      menthol) against six active species. A previous study has shown that the
      monoterpene linalool is a radioprotector for cellular systems, therefore, its
      scavenging ability was compared with known radioprotective agents such as
      cysteamine and amifostine. Results indicated that the monoterpene menthol but not
      linalool is a potent scavenger of reactive oxygen species and its scavenging
      magnitude is comparable to cysteamine and amifostine. This paper is first to show
      a correlation between ROS scavenging ability and radioprotective action.

PMID- 30098869
TI  - Design, synthesis and preclinical evaluation of 5-methyl-N4-aryl-furo[2,3
      d]pyrimidines as single agents with combination chemotherapy potential.
AB  - The design, synthesis and biological evaluation of 4-substituted 5-methyl
      furo[2,3-d]pyrimidines is described. The Ullmann coupling of 5-methyl-furo[2,3
      d]pyrimidine with aryl iodides was successfully optimized to synthesize these
      analogs. Compounds 6-10 showed single-digit nanomolar inhibition of EGFR kinase.
      Compounds 1 and 6-10 inhibited VEGFR-2 kinase better than or equal to sunitinib.
      Compounds 1 and 3-10 were more potent inhibitors of PDGFR-beta kinase than
      sunitinib. In addition, compounds 4-11 had higher potency in the CAM angiogenesis
      assay than sunitinib. Compound 1 showed in vivo efficacy in an A498 renal
      xenograft model in mice. Multiple RTK and tubulin inhibitory attributes of 1, 4,
      6 and 8 indicates that these compounds may be valuable preclinical single agents
      targeting multiple intracellular targets.

PMID- 30098870
TI  - Left Ventricular Myocardial Contractile Reserve during Exercise Stress in Healthy
      Adults: A Two-Dimensional Speckle-Tracking Echocardiographic Study.
AB  - BACKGROUND: The aims of the present study were to determine left ventricular (LV)
      myocardial contractile reserve during exercise stress testing in healthy adults
      and to evaluate the effects of gender and age on exercise LV global longitudinal
      strain (GLS). METHODS: The study population consisted of 67 healthy adults (age
      range, 23-80 years; 49% women). Subjects were analyzed with respect to gender and
      predefined age groups (age < 35 years, n = 18; age 35-55 years, n = 24; age > 55
      years, n = 25). All subjects underwent comprehensive echocardiographic assessment
      at rest and during symptom-limited semisupine exercise test. LV GLS was
      determined using two-dimensional speckle-tracking echocardiography. RESULTS: LV
      GLS magnitude during peak stress was 25.4 +/- 2.0%. The average absolute numeric
      LV GLS increase was 5.3%, equivalent to a relative 26.7% increase of LV GLS. LV
      GLS magnitude at peak exercise was without clinically significant differences
      between age groups (P = .07). No significant difference was found in peak
      exercise LV GLS between genders (P = .48). Linear regression analysis revealed a
      significant but weak correlation between peak LV GLS and age (r = -0.30, P =
      .02), whereas peak LV GLS was independent of maximal heart rate (r = 0.23, P =
      .07), peak mean arterial blood pressure (r = -0.11, P = .38), body mass index (r
      = 0.15, P = .22), and peak pulsed Doppler-derived cardiac index (r = -0.06, P =
      .67). CONCLUSIONS: LV GLS increases significantly during exercise stress in a
      healthy population. A dose-response relationship was found between LV GLS and
      exercise level independent of gender, and the influence of age appeared marginal.
      The technique is feasible, with low intra- and interobserver variability.

PMID- 30098872
TI  - Kvido Strisovsky: Casting the Spotlight on Intramembrane Proteases.

PMID- 30098873
TI  - Virtual histology uncertainty in synchrotron x-ray micro-computed tomography
      evaluation.
AB  - A three-dimensional (3D) X-ray tomogram evaluation gives a full view of the bone
      distribution around an entire implant in contrast to the often-used two
      dimensional (2D) histological methods. High-resolution X-ray absorption
      tomography was used to evaluate the 3D bone growth around dental implants in an
      experimental goat mandible reconstruction model. The tomograms allowed for the
      construction of virtual histological cross-sections that could be used to
      evaluate the statistical uncertainty of the histological methods, which was the
      purpose of this paper. The virtual 2D histological results showed a significantly
      higher uncertainty within the same sample than did the full 3D volume results.

PMID- 30098871
TI  - Three-Dimensional Mitral Valve Morphology in Children and Young Adults With
      Marfan Syndrome.
AB  - BACKGROUND: Mitral valve (MV) prolapse is common in children with Marfan syndrome
      (MFS) and is associated with varying degrees of mitral regurgitation (MR).
      However, the three-dimensional (3D) morphology of the MV in children with MFS and
      its relation to the degree of MR are not known. The goals of this study were to
      describe the 3D morphology of the MV in children with MFS and to compare it to
      that in normal children. METHODS: Three-dimensional transthoracic
      echocardiography was performed in 27 patients (3-21 years of age) meeting the
      revised Ghent criteria for MFS and 27 normal children matched by age (+/-1 year).
      The 3D geometry of the MV apparatus in midsystole was measured, and its
      association with clinical and two-dimensional echocardiographic parameters was
      examined. RESULTS: Compared with age-matched control subjects, children with MFS
      had larger 3D annular areas (P < .02), smaller annular height/commissural width
      ratios (P < .001), greater billow volumes (P < .001), and smaller tenting
      heights, areas, and volumes (P < .001 for all). In multivariate modeling, larger
      leaflet billow volume in MFS was strongly associated with moderate or greater MR
      (P < .01). Intra- and interuser variability of 3D metrics was acceptable.
      CONCLUSIONS: Children with MFS have flatter and more dilated MV annuli, greater
      billow volumes, and smaller tenting heights compared with normal control
      subjects. Larger billow volume is associated with MR. Three-dimensional MV
      quantification may contribute to the identification of patients with MFS and
      other connective tissue disorders. Further study of 3D MV geometry and its
      relation to the clinical progression of MV disease is warranted in this
      vulnerable population.

PMID- 30098874
TI  - Phacoemulsification with intraocular pinhole implantation associated with
      Descemet membrane endothelial keratoplasty to treat failed full-thickness graft
      with dense cataract.
AB  - We present a case in which a different approach was used to treat an eye with
      dense cataract associated with an irregular failed full-thickness corneal graft.
      After cataract surgery, a foldable intraocular pinhole was implanted in the
      capsular bag to treat the irregular corneal astigmatism. Next, a Descemet
      membrane endothelial keratoplasty graft was used to improve transparency in the
      failed penetrating keratoplasty. This approach addressed the cataract, irregular
      cornea, and failed graft through a standard 2.2 mm clear corneal
      phacoemulsification incision, thus avoiding open-sky surgical time and expediting
      visual rehabilitation.

PMID- 30098876
TI  - Visual and physiological outcomes of scleral lens wear.
AB  - PURPOSE: To describe patient-specific outcomes of scleral lens wear utilizing a
      variety of lens designs across multiple practice settings as reported in an
      international practitioner survey. METHODS: An electronic survey was administered
      to eye care providers who prescribe scleral lenses in which they were asked to
      describe their most recently examined established scleral lens patient. Data was
      collected on patient characteristics, lens designs, wearing schedules, care
      products, and visual and physiological outcomes of lens wear. Descriptive
      analysis of data was performed. RESULTS: A total of 292 responses were received.
      Participants represented 26 countries. The most commonly reported indication for
      scleral lens wear was corneal irregularity (87%) followed by ocular surface
      disease (8%), refractive error (4%) and 1% with multiple indications. Visual
      acuity improved from 0.4 +/- 0.4 (mean +/- SD) to 0.1 +/- 0.2 in eyes with
      corneal irregularity (p < 0.001), from 0.3 +/- 0.3 to 0.1 +/- 0.3 in eyes with
      ocular surface disease (p < 0.001), and from 0.1 +/- 0.1 to 0.0+/- [0.1] in eye
      with refractive error (p = 0.01). Prior to scleral lens wear, corneal staining
      was present in 55% of patients; staining was present in only 35% of patients
      following scleral lens wear. The number of topical ophthalmic drops needed
      decreased from 1.7 +/- 0.9 to 0.8 +/- 0.8 in patients with corneal irregularity
      (p < 0.001) and from 3.5 +/- 1.7 to 1.1 +/- 1.0 in patients with ocular surface
      disease (p < 0.001). The number of drops used by patients with refractive error
      remained stable, with these patients using an average of 2.0 +/- 1.0 drops prior
      to scleral lens wear and 1.7 +/- 1.5 drops following scleral lens wear.
      CONCLUSIONS: Patients with corneal irregularity experienced the greatest
      improvement in visual acuity, but patients with ocular surface disease and
      refractive error also achieved better visual acuity with scleral lenses. Ocular
      surface condition improved in patients with both corneal irregularity and ocular
      surface disease; patients with ocular surface disease experienced the most
      dramatic improvement. Patients who wore scleral lenses to correct uncomplicated
      refractive error did not experience an improvement in signs or symptoms of ocular
      surface disease.

PMID- 30098875
TI  - Factors Associated with Adherence to Mammography Screening Among Insured Women
      Differ by Income Levels.
AB  - BACKGROUND: Breast cancer is the second leading cause of cancer mortality, yet
      mammography screening rates remain less than optimal and differ by income levels.
      The purpose of this study was to compare factors predicting mammography adherence
      across income groups. METHODS: Women 41 to 75 years of age (N = 1,681) with
      health insurance and with no mammogram in the last 15 months were enrolled to
      participate in an interventional study. Binary logistic regression was used to
      estimate multivariable-adjusted odds ratios (ORs) for demographic and health
      belief factors predicting mammography adherence for each income group: 1) low,
      less than $30,000, 2) middle, $30,000 to 75,000, and 3) high, greater than
      $75,000 per year. RESULTS: Being in the contemplation stage (vs.
      precontemplation) of obtaining a mammogram predicted mammography adherence across
      all income groups and was the only predictor in the middle-income group (OR, 3.9;
      95% CI, 2.61-5.89). Increase in age was associated with 5% increase (per year
      increase in age) in mammography adherence for low-income (OR, 1.05; 95% CI, 1.01
      1.09) and high-income (OR, 1.05; 95% CI, 1.02-1.08) women. Having a doctor
      recommendation predicted mammography adherence only in low-income women (OR,
      10.6; 95% CI, 2.33-48.26), whereas an increase in perceived barriers predicted
      mammography adherence only among high-income women (OR, 0.96; 95% CI, 0.94-0.99).
      In a post hoc analysis, high-income women reported difficulty in remembering
      appointments (53%) and lack of time to get a mammogram (24%) as key barriers.
      CONCLUSIONS: For all income groups, being in contemplation of obtaining a
      mammogram predicted mammography adherence; however, age predicted mammography
      adherence for low- and high-income groups, whereas doctor recommendation and
      perceived barriers were unique predictors for low- and high-income women,
      respectively. Health care providers should be aware of differences in factors and
      emphasize strategies that increase mammography adherence for each income group.

PMID- 30098877
TI  - Low level laser therapy reduces oral leukoplakia lesion size: Results from a
      preliminary study.

PMID- 30098878
TI  - [An unusual lung cavity].

PMID- 30098879
TI  - [Mediastinitis following endobronchial ultrasound-guided transbronchial needle
      aspiration].
AB  - INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) is a minimally invasive procedure designed to explore mediastinal
      lymphadenopathy. Its use and indications have increased recently and severe,
      though rare, complications have been reported. CASE REPORT: EBUS-TBNA was
      performed in a 64-year-old patient presenting with mediastinal lymphadenopathy,
      probably due to sarcoidosis, but without histological proof. Within hours of the
      aspiration of subcarinal lymph nodes (station 7), the patient developed fever and
      dry cough associated with progressive dysphagia and dysphonia that persisted for
      four weeks. Mediastinitis was diagnosed after a CT-scan revealed a collection in
      the subcarinal space previously tapped using CT guidance. Intravenous antibiotics
      were started and both symptoms and the mediastinal collection resolved without
      need of a surgical procedure. The patient recovered fully. CONCLUSION: EBUS-TBNA
      is associated with a risk of mediastinitis that may manifest as an isolated fever
      arising within hours of the procedure. The pathogens responsible are usually
      contaminants from the oropharynx such as Streptococcus sp, probably inoculated
      directly into the mediastinum during transbronchial needle aspiration. Rapid
      diagnosis and treatment are necessary in order to reduce morbidity and mortality
      associated with mediastinitis.

PMID- 30098880
TI  - [Acquired hemophilia A revealing lung cancer].
AB  - : Acquired hemophilia A (AHA) is a rare disease, defined by the production of
      anti-factor VIII antibodies causing disordered hemostasis. It is idiopathic in
      50% of cases, but sometimes associated with solid tumors. We report a case where
      AHA led to the diagnosis of lung cancer. CASE REPORT: An 82-year-old man with
      spontaneous hematomas on his trunk and extremities, and isolated prolongation of
      activated partial thromboplastin time was admitted to the emergency room. A
      severely reduced factor VIII level and a high factor VIII inhibitor title
      confirmed the diagnosis of AHA. Thoracic computed tomography scan found a suspect
      lung nodule and biopsy was consistent with a primary lung adenocarcinoma. The
      patient received recombinant factor VIII, immunosuppressive therapies, and
      finally lung stereotactic radiotherapy. Thirty months after diagnosis, the
      patient is in complete remission both from AHA and from his lung cancer.
      CONCLUSIONS: Acquired hemophilia A is a rare but potentially severe disease,
      which may be idiopathic or linked to a solid tumor. The severity of AHA depends
      on both the volume of hemorrhage and the presence of associated diseases.

PMID- 30098881
TI  - [Assessment of insomnia among Tunisian patients with lung cancer].
AB  - INTRODUCTION: Sleep disorders are relatively common in oncology. However, they
      have not been well studied and are often treated insufficiently. AIM: To assess
      the prevalence and severity of insomnia in lung cancer patients and evaluate the
      relationship between insomnia and certain clinical parameters. METHODS: A cross
      sectional study was undertaken of patients in Tunis with primary lung cancer.
      Socio-demographic and clinical data were obtained from the medical records
      Patients were then asked to answer questionnaires related to insomnia (ISI),
      depression-anxiety (HAD) and quality of life (QLQ-C30). RESULTS: Fifty patients
      with lung cancer were included (46 men, 4 women). The average age was 59+/-9
      years. Insomnia was found in 24 patients (48%) and 60% of patients had
      depression. HAD was significantly higher in the insomniac patients (21.54+/-8.96
      vs. 9.81+/-5.28, P<0.0001). Similarly, the QLQ-C30 was significantly lower in
      these patients (41.24+/-12.55 vs. 56+/-16.88, P<0.01). ISI was significantly
      correlated with HAD and QLQ-C30. CONCLUSION: Insomnia is common in patients with
      lung cancer. It is responsible for impaired quality of life and psychological
      distress. Diagnosis and management of insomnia in patients with lung cancer is
      therefore mandatory.

PMID- 30098882
TI  - Expert Recommendations on the Interleukin 6 Blockade in Patients with Rheumatoid
      Arthritis.
AB  - OBJECTIVE: To draft recommendations on interleukin 6 (IL-6) blockade in
      rheumatoid arthritis (RA), based on best evidence and experience. METHODS: A
      group of 10 experts on IL-6 blockade in RA was selected. The 2 coordinators
      formulated 23 questions about IL-6 blockade (indications, efficacy, safety,
      etc.). A systematic review was conducted to answer the questions. Using this
      information, inclusion and exclusion criteria were established, as were the
      search strategies (Medline, EMBASE and the Cochrane Library were searched). Two
      different reviewers selected the articles. Evidence tables were created. At the
      same time, European League Against Rheumatism and American College of
      Rheumatology abstracts were evaluated. Based on this evidence, the coordinators
      proposed preliminary recommendations that the experts discussed and voted on in a
      nominal group meeting. The level of evidence and grade of recommendation were
      established using the Oxford Centre for Evidence Based Medicine and the level of
      agreement with the Delphi technique (2 rounds). Agreement was established if at
      least 80% of the experts voted yes (yes/no). RESULTS: The 8 preliminary
      recommendations were accepted after the Delphi process. They covered aspects such
      as the use of these therapies in monotherapy, in combination, in patients with
      refractory disease or intolerant patients, response evaluation, optimization and
      risk management. CONCLUSIONS: The manuscript aims to solve frequently asked
      questions and aid in decision making strategies when treating RA patients with IL
      6 blockade.

PMID- 30098883
TI  - Pseudomonas aeruginosa quorum sensing molecule N-3-oxo-dodecanoyl-l-homoserine
      lactone activates human platelets through intracellular calcium-mediated ROS
      generation.
AB  - Pseudomonas aeruginosa, an opportunistic pathogen release N-3-oxo-dodecanoyl-l
      homoserine lactone (3-oxo-C12HSL) and N-butyryl-l-homoserine lactone (C4-HSL)
      quorum sensing (QS) molecules to regulate various virulence factors responsible
      for infection in the host. 3-oxo-C12 HSL not only regulates the bacterial gene
      expression but also modulates the host cell system. Thus, it is pertinent to
      evaluate the effect of these QS molecules on blood platelets which is responsible
      for the maintenance of hemostasis and thrombus formation. Here, in the present
      study, we showed that 3-oxo-C12 HSL activates platelets in a dose-dependent
      manner and induces intracellular calcium-mediated reactive oxygen species (ROS)
      release, whereas no such effect was observed with C4-HSL. 3-oxo-C12 HSL
      stimulated ROS release was mediated by NADPH oxidase. Results confirmed the
      involvement of phospholipase C (PLC) and IP3 receptor behind intracellular
      calcium-mediated ROS generation. The impact of 3-oxo-C12 HSL on platelet
      activation suggests that it could interfere and alter the normal function of
      platelet in individuals infected with P. aeruginosa.

PMID- 30098884
TI  - Spectroscopic techniques investigation on the interaction of glucoamylase with 1
      deoxynojirimycin: Mechanistic and conformational study.
AB  - 1-Deoxynojirimycin (DNJ), a representative polyhydroxylated alkaloids, is widely
      used in the field of antidiabetic, antitumor, and anti-HIV. The present study
      tried to clarify the interaction mechanism of DNJ with glucoamylase by multi
      spectroscopic techniques, dynamic light scattering in combination with molecular
      modeling strategies from biophysics point of view. Fluorescence and UV-vis data
      indicated that fluorescence quenching mechanism of glucoamylase and DNJ was a
      dynamic manner. The association constant, binding site and thermodynamic
      parameters were also obtained from fluorescence spectrum at different
      temperatures. Synchronous fluorescence, circular dichroism and dynamic light
      scattering methods demonstrated that their interaction induced microenvironment
      changes around tryptophan residue and protein conformational alteration. The main
      driving force was hydrophobic interaction and hydrogen bonding. In addition,
      molecular docking study indicated that 1-deoxynojirimycin could bind in the
      catalytic domain of glucoamylase and interact with amino acid residues Arg78,
      Asp79, Glu203 and Glu424 by forming hydrogen bonds. Molecular dynamics simulation
      demonstrated that profiles of atomic fluctuation remained the rigidity of ligand
      binding site. This study elucidated the detailed interaction mechanism of DNJ
      with glucoamylase, which will be helpful for pharmaceutical companies to design
      new alpha-glucosidase inhibitor drugs based on polyhydroxylated alkaloids
      compound like DNJ.

PMID- 30098886
TI  - [Socio-cognitive determinants of intention to apply blood transfusion procedures:
      Survey in French public hospitals].
AB  - OBJECTIVES: Studies on blood transfusion reveal that specific rules are not
      always respected by healthcare professionals. This study aims to better
      understand the intention to apply the blood transfusion rules, and to examine,
      within the framework of the theory of planned behavior, the barriers and
      facilitators. METHODS: In total, 2604 healthcare professionals from 13 French
      public hospitals responded to this survey. The questionnaire included measures
      related to attitudes, pressure from colleagues/physicians/institutions, and
      factors related to the intention to apply haemovigilance rules. RESULTS: The
      majority of healthcare professionals (67 %) received blood transfusion safety
      training, 56 % reported compliance of blood transfusion procedures, and 24 %
      would never meet them or occasionally. The regression analyzes show that the
      factors related to training, age, frequency of blood transfusion explain very
      little behavioral intention. Professionals' attitudes (utility and perceived
      value of behavior) (beta=0.42) and peer pressure (beta=0.21) are major
      predictors. The barriers related to habits/beliefs (beta=-0.12), lack of time
      (beta=-0.12), pressure from institutions (beta=-0.05) also contribute, but to a
      lesser extent. CONCLUSIONS: The results confirm the theory of planned behavior
      showing that the intention to apply specific blood transfusion rules is related
      to attitude and social norms. These findings may encourage the development of
      networks of referents in healthcare units, and actions of prevention on the
      usefulness of blood transfusion rules.

PMID- 30098885
TI  - Current role of staple line reinforcement in 30-day outcomes of primary
      laparoscopic sleeve gastrectomy: an analysis of MBSAQIP data, 2015-2016 PUF.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has become a dominant bariatric
      procedure. In the past, significant leak rates prompted the search for staple
      line reinforcement (SLR) techniques. Previous analysis of the Metabolic and
      Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP)
      database for all LSG suggested a detrimental influence of SLR on leak rates and
      overall morbidity. OBJECTIVE: To investigate the relationship between various SLR
      techniques and bougie size with 30-day outcomes. SETTING: Metabolic and Bariatric
      Surgery Accreditation and Quality Improvement Program-accredited bariatric
      surgery hospitals. METHODS: Using the Metabolic and Bariatric Surgery
      Accreditation and Quality Improvement Program 2015 to 2016 Participant Use File
      data, primary LSG cases were divided into study groups based on surgical
      techniques. All variables were reported in the Participant Use File except leak
      rate and overall morbidity, which had to be derived. Multiple bivariate analyses
      were used to analyze the 30-day outcomes. RESULTS: A total of 198,339 primary LSG
      operations were included and grouped into No SLR (23.0%), SLR (54.2%), oversewn
      staple line (9.5%), and a combination of SLR + oversewn staple line (13.3%).
      There were no statistical differences between study groups in mortality, overall
      morbidity, or leak rate. Bleeding and reoperation rates were statistically higher
      in the No SLR group. Bougie size was not associated with change in leak rates.
      CONCLUSION: Primary LSG is a safe procedure with low morbidity and mortality
      rates. SLR is associated with decreased rates of bleeding and reoperations but
      does not affect leak rates. The selection of SLR technique should be left to the
      surgeon's discretion with an understanding of the associated risks, benefits, and
      costs.

PMID- 30098887
TI  - Feasibility of Dual Energy X-Ray Absorptiometry Based Images for Measurement of
      Height, Sitting Height, and Leg Length in Children.
AB  - BACKGROUND: Interpretation of pediatric bone mineral density by dual energy
      absorptiometry (DXA) requires adjustment for height (Ht). This is often not
      easily obtainable in nonambulant subjects. AIMS: To investigate the feasibility
      of using DXA images to evaluate measurements of Ht, sitting height (SH), and leg
      length (LL). METHODOLOGY: A total of 2 observers performed measurements of Ht,
      SH, and LL on 3 separate occasion using DXA digital images in 125 children.
      Intraclass correlation and relative technical error of measurement (rTEM) were
      performed to assess reliability of repeated measurements. In 25 children, Ht and
      SH were measured in clinic on the same day and Bland-Altman analysis was
      performed to compare DXA measured Ht, SH, LL with clinic measurements for these
      25 children. RESULTS: Intraclass correlation for DXA based Ht, SH, and LL
      measurements ranged from 0.996 to 0.998 (p < 0.0001). rTEM of Ht, SH, and LL for
      observer 1 was 0.0016%, 0.002%, and 0.0034%, respectively. rTEM of Ht, SH, and LL
      between observer 1 and 2 was 0.0047%, 0.0049%, and 0.0087%, respectively. Mean
      difference between clinic and DXA measurements from Bland-Altman plots were +0.57
      cm (95% confidence interval [CI] -0.54 to +1.68) for Ht, +1.33cm (-1.60 to +4.24)
      for SH, and -0.76cm (-3.88 to +2.37) for LL. CONCLUSIONS: Our study demonstrated
      for the first time that Ht, SH, and LL in children can be measured very precisely
      using DXA images. Ht can be measured accurately. We believe this may be a
      convenient method to obtain Ht measurements to allow size adjustment of DXA bone
      mineral density in immobile children with chronic conditions.

PMID- 30098888
TI  - Associations between recent and established ophthalmic conditions and risk of
      Alzheimer's disease.
AB  - INTRODUCTION: Identifying ophthalmic diseases associated with increased risk of
      Alzheimer's disease (AD) may enable better screening and understanding of those
      at risk of AD. METHODS: Diagnoses of glaucoma, age-related macular degeneration
      (AMD), and diabetic retinopathy (DR) were based on International Classification
      of Diseases, 9th revision, codes for 3877 participants from the Adult Changes in
      Thought study. The adjusted hazard ratio for developing probable or possible AD
      for recent (within 5 years) and established (>5 years) diagnoses were assessed.
      RESULTS: Over 31,142 person-years of follow-up, 792 AD cases occurred. The recent
      and established hazard ratio were 1.46 (P = .01) and 0.87 (P = .19) for glaucoma,
      1.20 (P = .12) and 1.50 (P < .001) for AMD, and 1.50 (P = .045) and 1.50 (P =
      .03) for DR. DISCUSSION: Increased AD risk was found for recent glaucoma
      diagnoses, established AMD diagnoses, and both recent and established DR. People
      with certain ophthalmic conditions may have increased AD risk.

PMID- 30098889
TI  - Evaluation of surgery and surgical results of Baha(r) Attract system
      implantations - single centre experience of hundred twenty five cases.
AB  - INTRODUCTION: Bone-anchored hearing aids are currently well-established solutions
      for treatment of hearing-impaired patients. OBJECTIVE: To evaluate the surgery of
      the Baha(r) Attract system, healing process and soft tissue condition after the
      processor activation. METHODS: 125 patients implanted with the Baha(r) Attract
      system during a 3 year period in a single ENT department were analysed. Evaluated
      parameters comprised: details of surgery, healing process and soft tissue
      condition at the time of the processor activation and on subsequent follow-up
      visits. RESULTS: The implantation was conducted under local anaesthesia in 96% of
      patients. The mean surgery time was 42min. Soft tissue reduction was performed in
      43.2% of cases; bone polishing in 23.2% and bipolar coagulation in all the cases.
      Healing was uneventful in 92.8%. 10 days after the surgery, pain was reported in
      48% of cases. On subsequent follow-up visits, 1 month and 3 months after the
      surgery, pain was present in 18.4% and 2.4% of cases respectively. Similarly,
      numbness and paresthesia, initially reported in 84% and 15.2%, were present in
      60% and 11.2% after a month, and in 17.6% and 1.6% after three months. After the
      processor attachment, no serious problems were observed in the analysed group
      during follow-up visits. However, mild redness and/or mild pain over the magnet
      were observed in 9.6% of patients. CONCLUSION: Implantation of the Baha(r)
      Attract system is an easy and safe procedure. It can be performed under local
      anaesthesia in adults. There are no major surgical problems or complications, and
      the healing process proceeds efficiently in most patients. Postoperative pain is
      usually mild and gradually decreases in the following months. Numbness in the
      operated area is frequent, but as reinnervation occurs in time, the numb patch
      decreases in size and finally completely disappears in most cases.

PMID- 30098890
TI  - Reply to Dr. Madias on "Autonomic adrenergic sympathetic hyperstimulation,
      myocardial edema, and "muscle cramps" in takotsubo syndome".

PMID- 30098903
TI  - [Sedentary lifestyle and urinary incontinence in women: A literature review].
AB  - AIM: The sedentary lifestyle is defined by a lack of regular mobilizing
      activities in the activities of daily life. The purpose of this work was to
      gather data related to the potential link between urinary incontinence and
      sedentary lifestyle in women. METHOD: A literature review (Pubmed/MEDLINE
      databases) based on keywords: women; urinary incontinence; sedentary; sedentary
      behavior; sedentary lifestyle; physical activity; exercise; sport, over the
      period 2008-2018 was carried out. RESULTS: Five cross-sectional observational
      studies were analyzed. Overall, the data supported a link between sedentary
      behavior and urinary incontinence in women. Several potential confounding factors
      (age, body mass index, comorbidities, lower socio-familial support) have been
      identified in the literature. Pathophysiological mechanisms remain poorly
      established, potentially including metabolic factors, postural factors and muscle
      dysfunctions. Few articles respected the strict definition of sedentary
      lifestyle, and no prospective study investigating the causal link between meddle
      or long-term sedentary was highlighted. CONCLUSION: The limited data available in
      the literature suggests that sedentary lifestyle is a risk factor for female
      urinary incontinence. Many confounding factors have been identified, justifying
      further studies evaluating more specifically the causal link between sedentary
      lifestyle and urinary incontinence in women.

PMID- 30098904
TI  - [Menthol in the control of bladder activity: A review].
AB  - INTRODUCTION: Menthol is a natural compound, of which the known effects on human
      physiology are manifold (a feeling of freshness, decongestant, bowel
      antispasmodic). Its implication in vesico-sphincteral physiopathology has been
      studied since the nineties. METHOD: Literature review of the previous studies
      having implied menthol in pelvi-perineal physiology through the articles indexed
      on the Pubmed database, with keywords menthol, menthol and bladder, menthol and
      toxicity, and TRPM8. Only articles in English were selected. RESULTS: Of the 30
      articles that were included, most demonstrated the existence of a micturition
      reflex to menthol and cold, mediated by the C-type nerve to the spine through
      activation of TRPM8 urothelial receptors. More recent experiments paradoxically
      showed an inhibitory effect of menthol on detrusor contractility, independently
      of TRPM8, when muscle tissue is directly exposed to the compound. However,
      similar effects of targeted cutaneous exposure or urothelial exposure on
      detrusorian function have also been demonstrated through TRPM8. This receptor
      also appears to be involved in interstitial cystitis and idiopathic detrusor
      overactivity. Lastly, the potential toxicity of menthol appears negligible. Most
      of the referenced studies are related to animal experiments. Of the three studies
      that implied humans, only one elucidates some therapeutic applications.
      CONCLUSION: It seems that menthol and its receptors are involved in vesico
      sphincteral physiopathology and could provide therapeutic potential in
      detrusorian overactivity and interstitial cystitis with reduced toxicity.

PMID- 30098905
TI  - "I just need to know they are going to do what they say they're going to do with
      my mom." Understanding hospice expectations from the patient, caregiver and
      admission nurse perspective.
AB  - OBJECTIVE: The objective of this paper is to understand patient, caregiver and
      hospice admission nurses needs during the hospice admission conversation so
      patients and their caregivers can make informed decisions about hospice. METHODS:
      Resulting data set from this qualitative study included 60 h of observation and a
      total of 30 interviews with caregivers, patients and hospice admission nurses.
      Participants were from a large non-profit hospice; observation settings included:
      home, hospital and skilled nursing facility. RESULTS: Four themes were
      identified: (1) Wide variation in patient knowledge of hospice care prior to the
      admission conversation, (2) competing expectations and objectives for the
      admission conversation between patients, caregivers and hospice admission team
      members, (3) organizational influences around the goals of the admission
      conversation, (4) importance of integrating the patient and caregiver perspective
      to improve the quality of admission conversations. CONCLUSION: Hospice services
      provided may be inconsistently explained by hospice personnel and therefore, can
      be misunderstood by patients and families. With the ubiquitous challenges
      surrounding hospice admission consults, there is a critical need for complete and
      accurate information during the admission process. PRACTICE IMPLICATIONS:
      Providing accurate and pertinent information at the time of the admission consult
      can help mitigate misinformed expectations of services provided.

PMID- 30098906
TI  - The Patient-Professional Interaction Questionnaire (PPIQ) to assess patient
      centered care from the patient's perspective.
AB  - OBJECTIVE: To investigate how patients evaluate the provision of patient-centered
      care (PCC) by healthcare professionals and psychometrically test a questionnaire
      to assess it. A tool previously developed for self-assessment of professionals'
      provision of PCC was adapted into a patient-rated form, named Patient
      Professional Interaction Questionnaire (PPIQ). METHODS: A sample of 1139 patients
      from six hospitals completed the 16-item PPIQ and the questionnaire structure,
      reliability, susceptibility to social desirability, and associations with other
      variables were tested. RESULTS: The PPIQ confirmed the original four-factor
      structure (effective communication, interest in the patient's agenda, empathy,
      and patient involvement in care) and showed acceptable reliability and
      measurement invariance across both in-/out-patients and first/non-first encounter
      with the evaluated professional. Associations with patients' social desirability
      were negligible and effective communication was rated the highest among the PPIQ
      dimensions. PPIQ scores varied according to patients' educational level and type
      of professional evaluated, while associations between first/non-first encounter
      and PPIQ scores varied according to in-/out-patient. CONCLUSION: The PPIQ is a
      psychometrically sound patient-rated measure of the provision of PCC by
      healthcare professionals. PRACTICE IMPLICATIONS: The PPIQ has potential value in
      promoting quality patient-professional interactions in the hospital setting, as
      patients' reported experience is an important dimension of the clinician's
      performance.

PMID- 30098907
TI  - Decision role preferences for return of results from genome sequencing amongst
      young breast cancer patients.
AB  - OBJECTIVE: To better understand decision role preferences in women diagnosed with
      breast cancer at a young age for return of results of genome sequencing in
      research and clinical settings. METHODS: Participants were surveyed about
      communication and decision-making preferences related to genome sequencing
      results and factors that may affect these preferences. The primary outcome was
      decision role preference (Control Preference Scale) for selecting what results to
      receive within medical care or within a research study. RESULTS: For results
      returned as part of medical care, most patients preferred a collaborative (N =
      481, 45%) or active (N = 488, 45%) role with only 107 (10%) choosing a passive
      role. When making the decision as part of a research study, most patients
      preferred an active role (N = 617, 57%), 350 (33%) choosing a collaborative role,
      and110 (10%) choosing a passive role. CONCLUSION: Most women in this study
      preferred to share in decision making. Participants had somewhat different role
      preferences for clinical and research contexts, with greater preference for
      active roles in the research context. PRACTICE IMPLICATIONS: We advocate for
      practice guidelines that incorporate discussion of decision role as an integral
      part of patient centered care and shared decision-making and recognize that more
      work is needed to inform guidelines.

PMID- 30098908
TI  - Monascus ruber: A new of onychomycosis in the north of Morocco (Tetouan).
AB  - We report a case of onychomycosis caused by Monascus ruber from 57-year old
      women. The diagnosis was based on culture morphological characteristics on
      Sabouraud's Dextrose agar one with antibacterial (chloramphenicol) and the other
      with cycloheximide. The identification of specie was confirmed by DNA sequencing.

PMID- 30098909
TI  - A new approach to testing the efficacy of drinking water disinfectants.
AB  - New disinfection procedures are being developed and proposed for use in drinking
      water production. Authorising their use requires an effective test strategy that
      can simulate conditions in practice. For this purpose, we developed a test rig
      working in a flow-through mode similar to the disinfection procedures in
      waterworks, but under tightly defined conditions, including very short contact
      times. To quantify the influence of DOC, temperature and pH on the efficacy of
      two standard disinfectants, chlorine and chlorine dioxide, simulated use tests
      were systematically performed. This test rig enabled quantitative comparison of
      the reduction of four test organisms, two viruses and two bacteria, in response
      to disinfection. Chlorine was substantially more effective against Enterococcus
      faecium than chlorine dioxide whereas the latter was more effective against the
      bacteriophage MS2, especially at pH values of >7.5 at which chlorine efficacies
      already decline. Contrary to expectation, bacteria were not generally reduced
      more quickly than viruses. Overall, the results confirm a high efficacy of
      chlorine and chlorine dioxide, validating them as standard disinfectants for
      assessing the efficacy of new disinfectants. Furthermore, these data demonstrate
      that the test rig is an appropriate tool for testing new disinfectants as well as
      disinfection procedures.

PMID- 30098910
TI  - Osthole inhibits pancreatic cancer progression by directly exerting negative
      effects on cancer cells and attenuating tumor-infiltrating M2 macrophages.
AB  - Pancreatic cancer has remained a major cause of cancer-related deaths. A hallmark
      of pancreatic cancer is extensive stromal reactions, resulting in a unique tumor
      microenvironment, especially the involvement of macrophages. These tumor-educated
      cells limit the efficacy of chemotherapy. Therefore, it is necessary to identify
      an effective treatment strategy. In this study, we aimed to explore the anti
      tumor and immunomodulatory effects of osthole on pancreatic cancer. We found that
      osthole suppressed Panc 02 cell migration and proliferation and induced apoptosis
      as shown in vitro. Osthole also attenuated the development of pancreatic cancer
      in mice by inhibiting tumor-infiltrating M2 macrophages in our study.
      Additionally, osthole inhibited the polarization of primary bone marrow cells
      into M2 macrophages and inhibited the expression of MRC1, CCL22 and TGF-beta in
      the M2 polarization process in vitro. Detection of the related signaling pathways
      revealed that osthole exerted immunomodulatory effects on M2 macrophages by down
      regulating p-STAT6 and the p-ERK1/2-C/EBP beta axis. These results indicated that
      osthole has effective anti-tumor and immunomodulatory effects on pancreatic
      cancer.

PMID- 30098911
TI  - Diallyl trisulfide regulates rat colonic smooth muscle contractions by inhibiting
      L-type calcium channel currents.
AB  - Diallyl trisulfide (DATS) is an active organosulfide component of allicin and has
      several beneficial effects, including antimicrobial, antioxidant,
      cardioprotective and anticancer effects. Few studies have shown the modulatory
      effect of DATS on L-type calcium channels in rat colonic smooth muscle cells and
      colonic motility. To investigate the modulatory effect of DATS on L-type calcium
      channels in rat colonic smooth muscle and colonic contraction, L-type calcium
      channel currents were recorded, and colonic contractility in longitudinal and
      circular smooth muscle strips was measured. DATS attenuated L-type calcium
      channel currents without affecting steady-state activation or inactivation
      kinetics and inhibited the spontaneous contractions of both longitudinal and
      circular smooth muscle strips dose-dependently. In conclusion, DATS has an
      inhibitory effect on the contractions of colonic muscle strips that is related to
      its regulation of L-type calcium channels.

PMID- 30098912
TI  - Anti-angiogenic and anticancer effects of baicalein derivatives based on
      transgenic zebrafish model.
AB  - Angiogenesis leads to tumor neovascularization by promoting tumor growth and
      metastatic spread, therefore, angiogenesis is considered as an attractive target
      for potential small molecule anticancer drug discovery. Herein, we report the
      structural modification and biological evaluation of baicalein derivatives, among
      which compound 42 had potent in vivo anti-angiogenic activity and wide security
      treatment window in transgenic zebrafish model. Further, 42 exhibited the most
      potent inhibitory activity on HUVEC proliferation, migration and tube formation
      in vitro. Moreover, 42 significantly inhibited growth of human lung cancer A549
      cells and weak influence on human normal fibroblast L929 cells. The present
      research demonstrated that the significant anti-angiogenic and anticancer
      effects, which provided the supportive evidence for 42 could be used as a
      potential compound of cancer therapy.

PMID- 30098913
TI  - Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and
      preliminary evaluation.
AB  - The treatment of glioma has become a great challenge because of the existence of
      brain barrier (BB). In order to develop an efficient brain targeting drug
      delivery system to greatly improve the brain permeability of anti-cancer drugs, a
      novel brain-targeted glucose-vitamin C (Glu-Vc) derivative was designed and
      synthesized as liposome ligand for preparing liposome to effectively deliver
      paclitaxel (PTX). The liposome was prepared and its particle size, zeta
      potential, encapsulation efficiency, release profile, stability, hemolysis and
      cytotoxicity were also characterized. What's more, the cellular uptake of CFPE
      labeled Glu-Vc-Lip on GLUT1- and SVCT2-overexpressed C6 cells was 4.79-, 1.95-,
      4.00- and 1.53-fold higher than that of Lip, Glu-Lip, Vc-Lip and Glu + Vc-Lip.
      Also, the Glu-Vc modified liposomes showed superior targeting ability in vivo
      evaluation compared with naked paclitaxel, non-coated, singly-modified and co
      modified by physical blending liposomes. The relative uptake efficiency was
      enhanced by 7.53 fold to that of naked paclitaxel, while the concentration
      efficiency was up to 7.89 times. What's more, the Glu-Vc modified liposomes also
      displayed the maximum accumulation of DiD-loaded liposomes at tumor sites with
      the strongest fluorescence in the brain in vivo imaging. Our results suggest that
      chemical modification of liposomes with warheads of glucose and vitamin C
      represents a promising and efficient strategy for the development of brain
      specific liposomes drug delivery system by utilizing the endogenous
      transportation mechanism of the warheads.

PMID- 30098914
TI  - Pathophysiology of severe fever with thrombocytopenia syndrome and development of
      specific antiviral therapy.
AB  - Severe fever with thrombocytopenia syndrome (SFTS) caused by SFTS virus (SFTSV),
      a novel phlebovirus, was reported to be endemic to central and northeastern PR
      China and was also to be endemic to South Korea and western Japan. SFTS is an
      emerging viral infection, which should be categorized as a viral hemorrhagic
      fever disease as Crimean-Congo hemorrhagic fever (CCHF) is caused by CCHF virus.
      SFTS is a tick-borne viral infection. SFTSV is maintained between several species
      of ticks and wild and domestic animals in nature. Patients with SFTS show
      symptoms of fever, general fatigue, and gastrointestinal symptoms such as bloody
      diarrhea. The severely ill SFTS patients usually show gastrointestinal hemorrhage
      and deteriorated consciousness. The case fatality rate of SFTS ranges from 5 to
      40%. Pathological studies on SFTS have revealed that the mechanisms behind the
      high case fatality rate are virus infection-related hemophagocytic syndrome
      associated with cytokine storm, coagulopathy due to disseminated intravascular
      coagulation causing bleeding tendency, and multi-organ failure. Favipiravir was
      reported to show efficacy in the prevention and treatment of SFTSV infections in
      an animal model. A clinical study to evaluate the efficacy of favipiravir in the
      treatment of SFTS patients has been initiated in Japan. SFTSV is circulating in
      nature in PR China, Korea, and Japan, indicating that we cannot escape from the
      risk being infected with SFTSV. The development of specific therapy and
      preventive measures is a pressing issue requiring resolution to reduce the
      morbidity and mortality of SFTS patients.

PMID- 30098915
TI  - Visceral leishmaniasis in hematopoietic cell transplantation: Case report and
      review of the literature.
AB  - Visceral leishmaniasis has been recognized as an opportunistic infection
      affecting people with cellular-immunity impairment, including hematopoietic cell
      transplantation (HCT) recipients. We describe the case of a young Italian man
      with Hodgkin lymphoma, who developed visceral leishmaniasis after multiple lines
      of chemotherapy and allogenic HCT. Literature review of visceral leishmaniasis in
      HCT recipients was also performed. Eleven patients (median age 50 years, 9 male)
      developed visceral leishmaniasis after allogenic (n = 9) and autologous (n = 2)
      HCT. Most of them presented with fever and pancytopenia. Bone marrow examination
      was the main diagnostic technique; liposomal amphotericin B was the treatment of
      choice. Four out of eight patients (for whom data are available) experienced
      visceral leishmaniasis relapse. Visceral leishmaniasis in HCT recipients is a
      rare event that should be suspected in patients with persistent fever,
      pancytopenia and possible exposure to Leishmania spp., remembering that - as well
      as South-East Asia, East Africa and South America - it is endemic in several
      European regions.

PMID- 30098916
TI  - An unusual case of cardiac tamponade: Bronchogenic cyst infection due to
      Salmonella bredeney.
AB  - We present an unusual case of cardiac tamponade in a 17-year-old girl
      immunocompetent patient due to Salmonella enterica ssp. bredeney following
      infection of a bronchogenic cyst. The patient was admitted to hospital with
      pleuritic chest pain, dyspnoea and fever. Pulmonary angio-CT showed a
      bronchogenic cyst compressing the left atrium. The echocardiography showed
      diffuse pericardial effusion with right ventricular collapse consistent with
      cardiac tamponade. Pericardiocentesis was performed and microbiological cultures
      of the pericardial fluid became positive for Salmonella species confirmed later
      as bredeney subspecies by PCR. Empirical antibiotherapy was started with
      intravenous (IV) ceftriaxone. Bronchogenic cyst infection was suspected and
      confirmed by 18FDG PET CT. The patient was successfully treated by complete
      resection of the cyst and continuation of IV ceftriaxone followed by oral
      amoxicillin/clavulanate for a total duration of 6 weeks. She then completely
      recovered and didn't present any relapse after 6 months of follow up.

PMID- 30098917
TI  - Comparative Study of Neoadjuvant Chemotherapy With and Without Zometa for
      Management of Locally Advanced Breast Cancer With Serum VEGF as Primary Endpoint:
      The NEOZOL Study.
AB  - INTRODUCTION: Neoadjuvant chemotherapy has become the treatment of choice for
      locally advanced breast cancer. Zoledronic acid (ZA) is a bisphosphonate
      initially used in the treatment of bone metastases because of its antibone
      resorption effect. Antitumor effects of ZA, including the inhibition of cell
      adhesion to mineralized bone or the antiangiogenic effect, have been
      demonstrated. However, the clinical significance of these effects remains to be
      determined. MATERIALS AND METHODS: We undertook a multicenter open-label
      randomized trial to analyze the value of adding ZA to neoadjuvant chemotherapy
      for TNM clinical stage T2/T3 breast cancer. The primary endpoint was the
      evolution of serum VEGF. RESULTS: The data from 24 patients were included in the
      ZA group and 26 in the control group. The evolution of serum VEGF was slightly in
      favor of ZA at 5.5 months (-0.7% vs. +7.5%), without reaching statistical
      significance (P = .52). The secondary endpoints were the breast conservation rate
      (higher with ZA; 83.3% vs. 65.4%; P = NS), pathologic complete response (no
      effect), and circulating tumor cells (odds ratio, 0.68 in favor of ZA; 95%
      confidence interval, 0.02-24.36). No cases of jaw necrosis or severe renal
      failure were observed in either group. CONCLUSION: ZA is an antitumor drug of
      interest because of its multiple effects on tumor biology. Larger trials with
      longer follow-up that include additional endpoints such as relapse and survival
      rates would be of interest.

PMID- 30098918
TI  - Novel Defense Peptides from Platelets Kill Malaria Parasites.
AB  - PF4 (platelet factor 4) is the first host defense peptide identified from
      platelets that kills malaria parasites. In a recent study, a cyclic PF4
      derivative, cPF4PD, is developed, which inherits the antiparasitic effect of PF4
      but excludes its potential side effects. cPF4PD is a promising novel antimalarial
      agent of human origin.

PMID- 30098919
TI  - Response to 'Re. Vascular Access: Clinical Practice Guidelines of the European
      Society for Vascular Surgery'.

PMID- 30098920
TI  - Letter to the Editor on the article "Sexual Health During Postgraduate Training
      European Survey Across Medical Specialties".

PMID- 30098921
TI  - Sleep quality and psychosocial characteristics of patients with painful post
      traumatic trigeminal neuropathies.
AB  - OBJECTIVES: The aim of this study was to explore how pain and psychological
      distress influence the sleep quality of patients with painful post-traumatic
      trigeminal neuropathy (PPTN). STUDY DESIGN: Thirty-two patients with a diagnosis
      of PPTN according to the International Classification for Headache Disorders of
      the International Headache Society were enrolled. All patients completed a number
      of questionnaires that examined sleep quality, psychological distress, and
      quality of life. RESULTS: The global Pittsburg Sleep Quality Index (PSQI) score
      was "5" or greater in 75% of the patients. Additionally, the Symptom Check List
      90-Revised (SCL-90-R) global severity index (GSI) revealed that 71.9% of the
      study sample reported values of psychological distress over the level of clinical
      significance. Sleep quality was analyzed through a linear regression model of
      global PSQI (dependent variable) that included gender, age, pain intensity, and
      pain duration (independent variables). This model revealed a significant positive
      association between the PSQI global score and the SCL-90-R GSI that was
      independent of age, gender, pain intensity, and duration. CONCLUSIONS: Patients
      with PPTN present higher levels of sleep disturbance and psychological distress
      compared with the general population. Sleep quality disturbances and levels of
      psychological distress are strongly associated and seem to be independent of age,
      gender, medication use, pain intensity and duration.

PMID- 30098922
TI  - Letter to the Editor regarding Ringenberg et al: "Interobserver and intraobserver
      reliability of radiographic classification of acromioclavicular joint
      dislocations".

PMID- 30098923
TI  - Increased scapular spine fractures after reverse shoulder arthroplasty with a
      humeral onlay short stem: an analysis of 485 consecutive cases.
AB  - BACKGROUND: Scapular stress fractures after reverse shoulder arthroplasty (RSA)
      are a potentially serious complication with modern lateralized and onlay
      implants. The aim of this study was to report the scapular spine stress fracture
      rate after RSA with an onlay, 145 degrees  humeral stem, analyzing potential
      fracture risk factors and clinical outcomes in a large cohort of patients.
      METHODS: A consecutive series of 485 RSAs were implanted with the Aequalis Ascend
      Flex stem. Data collection included preoperative and postoperative clinical and
      radiographic assessment findings (rotator cuff Goutallier grade; Hamada, Walch,
      and Favard classifications; range of motion; Constant score) and perioperative
      data. Patients with a scapular spine fracture following RSA were matched with
      nonfracture control patients, and preoperative variables were tested to determine
      whether they were predictive of a scapular spine fracture. RESULTS: A scapular
      spine fracture following RSA occurred in 21 patients (4.3%), with a mean time to
      diagnosis of 8.6 months (range, 1-34 months). No preoperative factor was found to
      be a significant predictor of scapular spine fracture. Both groups showed
      significant improvements in active mobility measurements and Constant scores from
      preoperatively to final follow-up (P < .001). The control group scored
      significantly better than the scapular spine fracture group regarding the
      Constant score and forward flexion. CONCLUSION: Scapular spine fractures have
      shown an increased prevalence after onlay-design RSA. This series was not able to
      link any clear risk factors. Functional results are limited, regardless of the
      fracture management.

PMID- 30098924
TI  - Letter to the Editor regarding Mahylis et al: "Hemolytic strains of
      Propionibacterium acnes do not demonstrate greater pathogenicity in
      periprosthetic shoulder infections".

PMID- 30098925
TI  - Reply.

PMID- 30098926
TI  - Reply.

PMID- 30098927
TI  - Reply.

PMID- 30098929
TI  - Very Early Versus Early Percutaneous Coronary Intervention After Successful
      Fibrinolytic Therapy in Pharmacoinvasive Strategy.
AB  - BACKGROUND: The proper time for the use of percutaneous coronary intervention
      (PCI) following the successful fibrinolysis for ST-segment elevation myocardial
      infarction (STEMI) for maximum efficiency and minimum side effects has not been
      determined yet. The present study was designed to compare the outcome of
      myocardial infarction patients who received fibrinolytic therapy with successful
      results and underwent PCI very early (within 3-12 h) (group 1) versus early
      (within 12-24 h) (group 2). METHODS: The study compared the occurrence of major
      adverse cardiac events during PCI (no-reflow phenomenon, access site bleeding,
      cerebral hemorrhage, and cardiac death). Patients were followed for 6 months
      after PCI for the occurrence of unstable angina, recurrent angina, non-STEMI,
      recurrent STEMI, repeat revascularization, heart failure, and cardiac death.
      RESULTS: Group 1 (121 patients) with the mean age of 59.93 +/- 10.43 years were
      compared with group 2 (144 patients) with the mean age of 62.84 +/- 10.22 years.
      Except for age, the 2 groups were not significantly different regarding baseline
      characteristics. No-reflow phenomenon was less in group 1 with p value = 0.005,
      whereas incidence of access site bleeding and cerebral hemorrhage were more in
      this group with p value = 0.001 and 0.049, respectively. During the period of 6
      months' follow-up, recurrent angina and recurrent non-STEMI occurred more in
      group 2 with p value = 0.049 and 0.035, respectively, with no other significant
      difference between the 2 groups. CONCLUSIONS: No-reflow phenomenon and the risk
      of recurrent ischemia is significantly lower in patients undergoing PCI very
      early after successful fibrinolytic therapy, but the risk of bleeding is
      increased in this time. So it is recommended that patients received successful
      fibrinolytic therapy to be subjected to very early PCI within 3 to 12 h from
      fibrinolysis.

PMID- 30098928
TI  - Individual islet respirometry reveals functional diversity within the islet
      population of mice and human donors.
AB  - OBJECTIVE: Islets from the same pancreas show remarkable variability in glucose
      sensitivity. While mitochondrial respiration is essential for glucose-stimulated
      insulin secretion, little is known regarding heterogeneity in mitochondrial
      function at the individual islet level. This is due in part to a lack of high
      throughput and non-invasive methods for detecting single islet function. METHODS:
      We have developed a novel non-invasive, high-throughput methodology capable of
      assessing mitochondrial respiration in large-sized individual islets using the
      XF96 analyzer (Agilent Technologies). RESULTS: By increasing measurement
      sensitivity, we have reduced the minimal size of mouse and human islets needed to
      assess mitochondrial respiration to single large islets of >35,000 MUm2 area
      (~210 MUm diameter). In addition, we have measured heterogeneous glucose
      stimulated mitochondrial respiration among individual human and mouse islets from
      the same pancreas, allowing population analyses of islet mitochondrial function
      for the first time. CONCLUSIONS: We have developed a novel methodology capable of
      analyzing mitochondrial function in large-sized individual islets. By
      highlighting islet functional heterogeneity, we hope this methodology can
      significantly advance islet research.

PMID- 30098930
TI  - Towards Universal Eye Health: Hospital-based disability-disaggregated data
      collection in Takeo province, Cambodia.
AB  - BACKGROUND: Universal access and equity are salient principles of the World
      Health Organization global action plan 'Towards Universal Eye Health'. However,
      collection of disability-disaggregated data to measure access to eye hospitals in
      low- and middle income countries, including referral to rehabilitative services,
      are not routinely integrated into Health Management Information Systems.
      OBJECTIVE: This report presents secondary-data analysis of disability
      disaggregated data collection that was introduced at a tertiary eye hospital in a
      rural province in Cambodia. METHODS: A modified version of the Washington Group
      Short Set of Questions was used to count the number of eye patients with self
      reported difficulties. The number of referrals of patients with unavoidable
      visual impairment to low vision services as well as referral to rehabilitative
      services was also counted. RESULTS: From 2011 to 2016, out of 182,327 patients
      overall 4981 (2.7%; 95% CI 2.66-2.81) reported difficulties with hearing, moving
      or communicating in addition to visual or other eye-related problems. Most of the
      difficulties were reported in the age group of patients aged 50 years and older
      (89.8% [95% CI 88.9-90.6]). All together 901 (0.5%; 95% CI 0.46-0.53) patients
      were treated at the low vision unit and 652 (0.36%; 95% CI 0.33-0.39) patients
      were referred to rehabilitation services. The number of referrals to
      rehabilitation declined annually from the year 2013-2016. CONCLUSIONS: Patients
      with self-reported impairments constitute a significant proportion of the eye
      hospital's population. A modified version of the Washington Group Short Set of
      Questions enabled routine disability-disaggregated data collection but resulted
      also in possible under-reporting of difficulties.

PMID- 30098931
TI  - Detection of Rickettsia monacensis and Rickettsia amblyommatis in ticks collected
      from dogs in Costa Rica and Nicaragua.
AB  - The neotropical climate of Central America provides ideal conditions for ticks,
      which may transmit several human pathogens, including spotted-fever group
      Rickettsia. Dogs may act as sentinels or reservoirs for human tick-borne diseases
      due to shared tick species. Here, ticks were collected from 680 client-owned dogs
      in Nicaragua and Costa Rica, and a total of 316 tick pools were investigated for
      Rickettsia infection by quantitative real-time PCR (qPCR) targeting the gltA
      gene. Subsequently, up to six further genomic targets (16S rDNA, gltA, sca4,
      ompA, ompB and the 23S-5S intergenic spacer) were investigated for Rickettsia
      species determination. The predominant tick species was Rhipicephalus sanguineus
      sensu lato (s.l.) (19.9% of dogs infested in Costa Rica, 48.0% in Nicaragua),
      followed by Ixodes boliviensis (3.1% in Costa Rica / none in Nicaragua) and
      Amblyomma ovale (4.8% in Costa Rica, 0.9% in Nicaragua). In total, 22 of 316 tick
      pools containing 60 of 1023 individual ticks were Rickettsia-positive as
      determined by qPCR, resulting in a minimum infection rate (MIR) of 2.2%. In
      detail, MIR in Rh. sanguineus s.l. was 0.7% (7/281 pools), in I. boliviensis
      33.3% (12/13 pools) and in A. ovale 9.7% (3/22 pools). For 11 of 12 positive I.
      boliviensis pools and one of six positive Rh. sanguineus s.l. pools, the species
      could be determined as R. monacensis. R. amblyommatis was identified in one Rh.
      sanguineus s.l. pool from Costa Rica and one A. ovale pool from Nicaragua. Nine
      of 12 R. monacensis-positive tick pools were collected in San Rafael de Heredia,
      Costa Rica, indicating a high local occurrence in this area. This study supports
      recent evidence that R. monacensis is present on the American continent. Its high
      local occurrence among dog-associated I. boliviensis, which may also parasitize
      humans, in Costa Rica gives cause for concern, as R. monacensis is also
      pathogenic to humans.

PMID- 30098932
TI  - Cost-effectiveness of Evolocumab. Response.

PMID- 30098934
TI  - The open door policy - An important and under-recognised activity of the adult CF
      centre.

PMID- 30098933
TI  - Objective Assessment of the Early Stages of the Learning Curve for the Senhance
      Surgical Robotic System.
AB  - OBJECTIVE: The purpose of this research is to study the early stages of the
      Senhance learning curve to report how force feedback impacts learning rate. This
      serves as an exploratory investigation into assumptions that fellows and faculty
      will adjust faster to the Senhance in comparison with residents, and that force
      feedback will not hinder skill acquisition. DESIGN: In this study, participants
      completed the peg transfer and precision cutting task from the Fundamentals of
      Laparoscopic Surgery (FLS) manual skills assessment five times each using the
      Senhance while instrument motion was tracked. SETTING: This study took place in
      the Surgical Education and Activities Laboratory at Duke University Medical
      Center. PARTICIPANTS: Participants for this study were residents, fellows, and
      faculty from Duke University Medical Center in general surgery and gynecology
      specialties (N = 16). RESULTS: Postulated linear mixed effects models with
      participant level random effects showed significant improvement with additional
      attempts for the peg transfer task after adjusting for surgical experience and
      force feedback respectively for the primary FLS score metric. The secondary
      metric of total instrument path length also showed improvement (significant
      decreases) in path length with additional attempts after respectively adjusting
      for surgical experience and force feedback. CONCLUSIONS: This study investigates
      the early stages of the learning curve of the Senhance. Exploratory modeling
      indicates that residents, fellows, and faculty surgeons rapidly adapt to the
      controls of the Senhance regardless of experience level and force feedback
      engagement. The results from this study may serve as motivation for future
      prospective studies that achieve sufficient statistical power with a larger
      sample size and strict experimental design.

PMID- 30098935
TI  - A spatial filtering approach to environmental emotion perception based on
      electroencephalography.
AB  - Studies have demonstrated that visual built environments can affect the emotions
      of individuals, which can be recorded and investigated using
      electroencephalography (EEG). To study emotional intensity in adolescents exposed
      to different visual built environments, we proposed an EEG-based spatial
      filtering method using Independent Component Analysis (ICA). Specifically, to
      identify effective video stimuli to induce emotions, we first developed a
      stimulus selection strategy using the normalized valence/arousal space model.
      Subsequently, we designed an optimum ICA-based spatial filter by analyzing
      independent component-to-electrode mapping patterns in different emotional
      states. Based on this, EEG signals with five emotional intensities in terms of
      arousal and valence dimensions were linearly projected by the designed filter to
      extract feature parameters. Finally, we used the Support Vector Model as the
      classifier to recognize emotions. In the laboratory environment, the average
      recognition accuracy ratios for the valence and arousal dimensions were 73.35%
      and 68.54% (within-participant test) and 66.98% and 62.62% (between-participant
      test), respectively, for the 10 participants. The experimental results validated
      the feasibility of the proposed ICA-based spatial filtering algorithm for
      emotional intensity recognition.

PMID- 30098936
TI  - The influence of bileaflet prosthetic aortic valve orientation on the blood flow
      patterns in the ascending aorta.
AB  - We investigate three-dimensional pulsatile aortic flow in the ascending aorta
      with mechanical prosthetic aortic valve implanted at two different orientations
      under physiological flow conditions using an anatomically accurate aorta. We
      perform 3D Particle Tracking Velocimetry measurements to assess the phase
      averaged and fluctuating velocity patterns as well as the shear stresses. A St
      Jude Medical prosthetic heart valve is implanted in an anatomically accurate
      silicone model of an aorta obtained from high resolution magnetic resonance
      imaging of a healthy proband at two different orientations. Our results show that
      the mechanical prosthetic valve orientation has considerable impact on the local
      kinetic energy and shear stress distributions but minor effects on the spatially
      averaged kinetic energy (10%) and shear stresses (15%). We show that the valve
      orientation plays a distinct role in spatial distribution of wall shear stresses
      and vortical structures. We show that our results, which show good agreement with
      the in silico and in vitro studies in the literature, provide full 3D kinetic
      energy and shear stress information over the entire cardiac cycle for different
      bileaflet prosthetic valve orientations under physiological flow conditions.

PMID- 30098937
TI  - An interpolation technique to enable accurate three-dimensional joint kinematic
      analyses using asynchronous biplane fluoroscopy.
AB  - Biplane 2D-3D model-based registration and radiostereometric analysis (RSA)
      approaches have been commonly used for measuring three-dimensional, in vivo joint
      kinematics. However, in clinical biplane systems, the x-ray images are acquired
      asynchronously, which introduces registration errors. The present study
      introduces an interpolation technique to reduce image registration error by
      generating synchronous fluoroscopy image estimates. A phantom study and cadaveric
      shoulder study were used to evaluate the level of improvement in image
      registration that could be obtained as a result of using our interpolation
      technique. Our phantom study results show that the interpolated bead tracking
      technique was in better agreement with the true bead positions than when
      asynchronous images were used alone. The overall RMS error of glenohumeral
      kinematics for interpolated biplane registration was reduced by 1.27 mm, 0.40 mm,
      and 0.47 mm in anterior-posterior, superior-inferior, and medial-lateral
      translation, respectively; and 0.47 degrees , 0.67 degrees , and 0.19 degrees  in
      ab-adduction, internal-external rotation and flexion-extension, respectively,
      compared to asynchronous registration. The interpolated biplane registration
      results were consistent with previously reported studies using custom synchronous
      biplane fluoroscopy technology. This approach will be particularly useful for
      improving the kinematic accuracy of high velocity activities when using clinical
      biplane fluoroscopes or two independent c-arms, which are available at a number
      of institutions.

PMID- 30098938
TI  - Predicting Response to Intravesical Therapy in Non-muscle-invasive Bladder
      Cancer.
AB  - CONTEXT: The ability to predict response to intravesical therapy (IVT) following
      transurethral resection in non-muscle-invasive bladder cancer holds important
      prognostic information. However, few predictive tools are available to guide
      urologists. OBJECTIVE: We reviewed the most recent studies investigating the
      predictors of response to IVT. EVIDENCE ACQUISITION: A literature search was
      conducted using PubMed database from January 1, 2013 to April 1, 2018 following
      the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)
      criteria. For our search strategy, we used the combination of the MeSH terms of
      "Administration, Intravesical" and "Urinary Bladder Neoplasms" with any of the
      following words: "Biomarkers," "Predictive Value of Tests," "response,"
      "recurrence," and "progression." We limited our search to the English language.
      EVIDENCE SYNTHESIS: Risk stratification models utilizing clinicopathological
      features are the most cost-effective and widely used tools currently available to
      predict response to IVT. Additionally, urinary fluorescence in situ hybridization
      testing and urinary cytokine-based nomograms (Cytokine Panel for Response to
      Intravesical Therapy) may enhance predictive ability. Protein-based biomarkers
      have been associated with predicting recurrence. Several gene-based biomarkers
      quantifying mutations in DNA damage repair genes may have predictive ability.
      However, genomic data are relatively new and lack validation. CONCLUSIONS:
      Clinicopathological criteria remain the most widely utilized tool for predicting
      IVT response. Further research to validate protein- and genomic-based biomarkers
      are needed before adoption in clinical practice. PATIENT SUMMARY: We reviewed
      contemporary studies that investigated how to predict response to medication
      instilled in the bladder (intravesical therapy) for bladder cancer. We found that
      most predictive tools use clinical data, such as tumor stage and grade, to
      determine the outcome. Newer biological (gene, protein, cytokines) marker tests
      are being studied. We concluded that the combination of clinical data with levels
      of certain experimental markers (fluorescence in situ hybridization test or
      urinary cytokines) may improve predictive ability. Genetic testing methods may
      also yield additional predictive markers in the future, but this needs more
      validation.

PMID- 30098939
TI  - Self-perceived body image, dissatisfaction with body weight and nutritional
      status of Brazilian adolescents: a nationwide study.
AB  - OBJECTIVES: The purpose of this study was to evaluate the agreement and risk
      factors for underestimation and overestimation between nutritional status and
      self-perceived body image and to assess the prevalence and associated factors for
      dissatisfaction with body weight among Brazilian adolescents. METHODS: Students
      aged 12-17 years participating in the Study of Cardiovascular Risk in Adolescents
      ("ERICA"), a multicenter, cross-sectional, school-based country-wide study, were
      included (n=71,740). Variables assessed as covariates were sex, age, skin color,
      socioeconomic status, and common mental disorders (screened by the General Health
      Questionnaire, GHQ-12). Multinomial logistic regression was used to explore the
      association between covariates and combinations between self-perceived body image
      and body mass index (agreement, underestimation and overestimation). The
      associations between dissatisfaction with body weight and exposure variables were
      investigated using multivariable Poisson regression models. RESULTS:
      Approximately 66% students rightly matched their body mass index with self
      perceived weight (kappa coefficient was 0.38 for boys and 0.35 for girls).
      Agreement was higher among younger students and adolescents from low income
      households. Male sex, older age, and GHQ-12 score >=3 were associated with weight
      overestimation. Prevalence of dissatisfaction with body weight was 45.0% (95% CI:
      44.0-46.0), and higher among girls, older adolescents, those with underweight or
      overweight/obesity, as well as those who were physically inactive and with GHQ-12
      >=3. CONCLUSIONS: Most of the sample rightly self-perceived their body image
      according to body mass index. Students with body image misperception and those
      dissatisfied with their weight were more likely to present a positive screening
      for common mental disorders.

PMID- 30098940
TI  - Is contraceptive self-injection cost-effective compared to contraceptive
      injections from facility-based health workers? Evidence from Uganda.
AB  - OBJECTIVE: To assess the cost-effectiveness of self-injected subcutaneous depot
      medroxyprogesterone acetate (DMPA-SC) compared to health-worker-administered
      intramuscular DMPA (DMPA-IM) in Uganda. STUDY DESIGN: We developed a decision
      tree model with a 12-month time horizon for a hypothetical cohort of
      approximately 1 million injectable contraceptive users in Uganda to estimate the
      incremental costs per pregnancy averted and per disability-adjusted life year
      (DALY) averted. The study design derived model inputs from DMPA-SC self-injection
      continuation and costing research studies and peer-reviewed literature. We
      calculated incremental cost-effectiveness ratios from societal and health system
      perspectives and conducted one-way and probabilistic sensitivity analyses to test
      the robustness of results. RESULTS: Self-injected DMPA-SC could prevent 10,827
      additional unintended pregnancies and 1620 maternal DALYs per year for this
      hypothetical cohort compared to DMPA-IM administered by facility-based health
      workers. Due to savings in women's time and travel costs, under a societal
      perspective, self-injection could save approximately US$1 million or $84,000 per
      year, depending on the self-injection training aid used. From a health system
      perspective, self-injection would avert more pregnancies but incur additional
      costs. A training approach using a one-page client instruction sheet would make
      self-injection cost-effective compared to DMPA-IM, with incremental costs per
      pregnancy averted of $15 and per maternal DALY averted of $98. Sensitivity
      analysis showed that the estimates were robust. The one-way and probabilistic
      sensitivity analyses showed that the costs of the first visit for self-injection
      (which include training costs) were an important variable impacting the cost
      effectiveness estimates. CONCLUSIONS: Under a societal perspective, self-injected
      DMPA-SC averted more pregnancies and cost less compared to health-worker
      administered DMPA-IM. Under a health system perspective, self-injected DMPA-SC
      can be cost-effective relative to DMPA-IM when a lower-cost visual aid for client
      training is used. IMPLICATIONS: Self-injection has economic benefits for women
      through savings in time and travel costs, and it averts additional pregnancies
      and maternal disability-adjusted life years compared to health-worker
      administered injectable DMPA-IM. Implementing lower-cost approaches to client
      training can help ensure that self-injection is also cost-effective from a health
      system perspective.

PMID- 30098942
TI  - Efficiency of flubendazole-loaded mPEG-PCL nanoparticles: A promising formulation
      against the protoscoleces and cysts of Echinococcus granulosus.
AB  - None of the existing drugs can effectively treat the human cystic echinococcosis.
      This study aimed to improve the efficacy of flubendazole (FLBZ) against the
      protoscoleces and cysts of Echinococcus granulosus by preparing polymeric FLBZ
      loaded methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) nanoparticles. The
      protoscoleces and microcysts were treated with FLBZ-loaded mPEG-PCL nanoparticles
      (FLBZ-loaded nanoparticles) and free FLBZ at the final concentrations of 1, 5,
      and 10 MUg/mL for 27 and 14 days, respectively. The chemoprophylactic efficacy of
      the drugs was evaluated in experimentally infected mice. The nanoparticles were
      stable for 1 month, with an average size of 101.41 +/- 5.14 nm and a zeta
      potential of -19.13 +/- 2.56 mV. The drug-loading and entrapment efficiency of
      the FLBZ-loaded nanoparticles were calculated to be 3.08 +/- 0.15% and 89.16 +/-
      2.93%, respectively. The incubation of the protoscoleces with the 10 MUg/mL nano
      formulation for 15 days resulted in 100% mortality, while after incubation with
      the 10 MUg/mL free FLBZ, the viability rate of the protoscoleces was only 44.0%
      +/- 5.22%. Destruction of the microcysts was observed after 7 days' exposure to
      the FLBZ-loaded nanoparticles at a concentration of 10 MUg/mL. The in vivo
      challenge showed a significant reduction in the weight and number of the cysts (P
      <  0.05) in the mice treated with the FLBZ-loaded nanoparticles, yielding
      efficacy rates of 94.64% and 70.21%, correspondingly. Transmission electron
      microscopy revealed extensive ultrastructural damage to the cysts treated with
      the FLBZ-loaded nanoparticles. The results indicated that the FLBZ-loaded
      nanoparticles were more effective than the free FLBZ against the protoscoleces
      and cysts of E. granulosus both in vitro and in vivo.

PMID- 30098941
TI  - Novel organic salts based on quinoline derivatives: The in vitro activity trigger
      apoptosis inhibiting autophagy in Leishmania spp.
AB  - Leishmaniases are infectious diseases, caused by protozoa of the Leishmania
      genus. These drugs present high toxicity, long-term administration, many adverse
      effects and are expensive, besides the identification of resistant parasites. In
      this work, the antileishmanial activity of quinoline derivative salts (QDS) was
      evaluated, as well as the toxicity on mammalian cells and the mechanism of action
      of the most promising compound. Among the compound tested, only the compound QDS3
      showed activity against promastigotes and amastigotes of Leishmania spp., being
      more active against the intracellular amastigotes of L. amazonensis-GFP (IC50 of
      5.48 MUM). This value is very close to the one observed for miltefosine (IC50 of
      4.05 MUM), used as control drug. Furthermore, the compound QDS3 exhibited a
      selective effect, being 40.35 times more toxic to the amastigote form than to the
      host cell. Additionally, promastigotes of L. amazonensis treated with this
      compound exhibited characteristics of cells in the process of apoptosis such as
      mitochondrial membrane depolarization, mitochondrial swelling, increase of ROS
      production, phosphatidylserine externalization, reduced and rounded shape, and
      cell cycle alteration. The integrity of the plasma membrane remained unaltered,
      excluding necrosis in treated promastigotes. The compound QDS3 inhibited the
      formation of autophagic vacuoles, which may have contributed to parasite death by
      preventing autophagic mechanisms in the removal of damaged organelles,
      intensifying the damage caused by the treatment, highlighting the antileishmanial
      effect of this compound. In addition, treatment with QDS3 induced increased ROS
      levels in L. amazonensis-infected macrophages, but not in uninfected host cell.
      These data reinforce that the induction of oxidative stress is one of the main
      toxic effects caused by the treatment with the compound QDS3 in L. amazonensis,
      causing irreversible damage and triggering a selective death of intracellular
      parasites. Data shown here confirm the biological activity of quinoline
      derivatives and encourage future in vivo studies with this compound in the murine
      model.

PMID- 30098943
TI  - Evaluation of Opisthorchis viverrini calreticulin for potential host modulation.
AB  - The multifunctional calreticulin (CALR) was identified as a major calcium-binding
      protein of the endoplasmic reticulum before being recognized as a chaperone in
      the same place. Only later were activities of calreticulin outside the
      endoplasmic reticulum described that for example affect cell proliferation and
      the innate immune system. In the present work we have investigated those
      extracellular activities of CALR from the cancerogenic human liver fluke
      Opisthorchis viverrini (OvCALR), as they might be important in host/parasite
      interaction. We first demonstrate that OvCALR is released from the parasite and
      stimulates a specific humoral immune response. Recombinant OvCALR is then shown
      to suppress proliferation of primary endothelial cells, their motility and
      sprouting activities. The potential of OvCALR to interfere with the complement
      system is established, firstly by demonstrating its direct binding to C1q and,
      secondly by suppression of hemolysis of sensitized red blood cells. These
      findings suggest that OvCALR is an important parasite antigen that could modulate
      diverse host functions and support parasite survival.

PMID- 30098944
TI  - Characterization of self-assembled hybrid siloxane-phosphocholine bilayers.
AB  - We have synthesized six new hybrid siloxane phosphocholines (SiPCs) and examined
      their self-assembly behaviour in aqueous dispersions. Employing small angle X-ray
      scattering we have characterized SiPC bilayers. SiPCs exhibit differential self
      assembly behaviour that results from the interplay between the siloxane fatty
      acid in the sn-2 position and the differing chain length fatty acids in the sn-1
      position. SiPCs that possess a fatty acid chain of a C8-C14 chain length in the
      sn-1 position form unilamellar vesicles. Extending the fatty acid chain length to
      C16 and C18 allows for the formation of both unilamellar and multilamellar
      vesicles. We propose that the preferential formation of unilamellar vesicles is
      the result of an enhanced hydrophobic effect imparted by siloxane chains at the
      termini of lipid tails.

PMID- 30098945
TI  - Aggressive behavior after social exclusion is linked with the spontaneous
      initiation of more action-oriented coping immediately following the exclusion
      episode.
AB  - The experience of social exclusion may provoke prosocial, avoidant, or antisocial
      (aggressive) behaviors. Multiple situational and personal factors seem to affect
      which course of action people adopt, and to which degree. The present study
      examined the relevance of the most spontaneous initiation of more passive,
      avoidant (disengagement) or action-oriented (engagement) coping immediately
      following a social exclusion experience to subsequent aggressive behavior. In a
      sample of n = 85 healthy female students, an ostensible discussion group excluded
      (versus included) the participant on the basis of her personal traits and
      preferences. The dynamics of heart rate changes immediately following the social
      exclusion episode yielded information on the most spontaneous preparation for
      passive, avoidant coping (sustained heart rate deceleration, indicating temporary
      behavioral inhibition and vigilance, "freezing") or action-oriented coping (heart
      rate acceleration, indicating mobilization for action, "fighting"). Aggressive
      tendencies following social exclusion were assessed using the hot sauce paradigm.
      On average, social exclusion was followed by heart rate deceleration, indicating
      the spontaneous drive to avoid directly dealing with the threat (F(time by
      condition) = 3.3, p = .017, eta2 = 0.038). A less pronounced cardiac slowing or
      even accelerative response to the exclusion, however, was associated with more
      subsequent aggressive behavior (r = 0.35, p = .023). The results indicate that
      individual differences in exclusion-related antisocial responding are in part
      already initiated instantaneously following the exclusion experience, before
      conscious interpretation and regulation efforts can take effect and modulate the
      behavioral outcome. The findings point to a potentially important factor that, in
      concert with other determinants, may explain interindividual differences in
      changes of social behavior following the experience of social exclusion.

PMID- 30098946
TI  - Possible evidence for care and treatment in the Tyrolean Iceman.
AB  - The Tyrolean Iceman is the world's oldest glacier mummy. He was found in
      September 1991 in the Italian part of the Otztal Alps. Since his discovery a
      variety of morphological, radiological and molecular analyses have been performed
      that revealed detailed insights into his state of health. Despite the various
      pathological conditions found in the Iceman, little is known about possible forms
      of care and treatment during the Copper Age in Northern Italy. A possible
      approach to this topic is the presence of tattoos on the mummified body. In
      previous work, it was already believed that the tattoos were administered as a
      kind of treatment for his lower back pain and degenerative joint disease of his
      knees, hip and wrist. In other studies, the tattoos of the Iceman have been
      related to an early form of acupuncture. We carefully re-evaluated the various
      health issues of the Iceman, including joint diseases, gastrointestinal problems
      and arterial calcifications and compared them to the location and number of
      tattoos. Together with the finding of medically effective fungi and plants, such
      as the birch polypore or fern in his equipment and intestines, we suggest that
      care and treatment was already common during the Iceman's time.

PMID- 30098947
TI  - An Inflammatory Bowel Disease Mimic in a Patient With Human Immunodeficiency
      Virus.

PMID- 30098948
TI  - Editorial Comment.

PMID- 30098949
TI  - Editorial Comment.

PMID- 30098950
TI  - Editorial Comment.

PMID- 30098951
TI  - Investigation of transition ion ratio variation for liquid chromatography-tandem
      mass spectrometry: A case study approach.
AB  - BACKGROUND: A transition ion ratio (TIR) is the ratio of one fragment over
      another from the same precursor and is frequently monitored in liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) assays for analyte
      identification. The Clinical and Laboratory Standards Institute (CLSI) C50-A
      guidelines give a static percent allowable TIR deviation based on the TIR level.
      Anecdotally, we observed failures of these rules for some of our LC-MS/MS assays.
      We determined what parameters may affect TIRs in a clinical setting and whether
      TIR variations may be analyte, matrix, instrument service, and/or concentration
      dependent. METHODS: Data was collected from the validation and selected periods
      after implementation for urine benzodiazepines (7 analytes) and plasma azole
      antifungals (6 analytes). TIRs for the calibrators and quality control materials
      on a Thermo TSQTM Quantum Ultra from July 2016 to February 2017 for
      benzodiazepines in urine and Thermo TSQTM Vantage from May 2016 to Oct 2016 for
      azoles in serum were monitored. RESULTS: The statistically significant day-to-day
      TIR shift ranged from 5.7 to 27.0% of the days studies for benzodiazepines and
      from 5.6 to 27.8% of the days studied for azoles excluding shifts caused by
      instrument services. Instrument service had significant impact on all
      benzodiazepines except oxazepam with p-values ranging from 1.79 * 10-6 to 1.53 *
      10-39 and 4 of the 6 azoles (fluconazole, isavuconazole, voriconazole, and
      itraconazole) with (p from 7.89 * 10-3 to 1.98 * 10-12). Lorazepam, alpha
      hydroxyalprazolam, and hydroxyitraconazole showed significant concentration
      dependent TIR variations. CONCLUSIONS: TIR variations may be affected by
      instrument services, and can be concentration and analyte dependent. Instead of
      using a static percent deviation rule, establishment of TIR variation criteria
      for each analyte during test development and validation may provide a more useful
      tool for analyte identification.

PMID- 30098953
TI  - Increasing incidence of cancer in children and competing risks.

PMID- 30098954
TI  - Malignant Hyperthermia: A Case Report in a Trauma Patient.
AB  - Malignant hyperthermia is a rare condition that occurs in susceptible patients
      exposed to triggering anesthetic agents. It is associated with a high mortality
      rate if not recognized immediately and treated appropriately. A 52-year-old man
      presented to our clinic 2 days after an assault for management of jaw pain. A
      minimally displaced right parasymphyseal fracture and moderately displaced left
      body fracture of the mandible were diagnosed. There were no known drug allergies.
      The patient reported no previous difficulty with anesthesia, as well as no known
      prior adverse reactions to anesthesia in any relatives. The planned surgical
      intervention was open reduction-internal fixation of bilateral mandibular
      fractures. The patient received succinylcholine and desflurane during the
      procedure. A full 70 minutes elapsed before initial signs of hypermetabolism were
      noted, namely a rise in end-tidal carbon dioxide level. The patient received
      dantrolene sodium approximately 120 minutes after induction of anesthesia. Signs
      of hypermetabolism began to abate within 45 minutes of commencement of the
      malignant hyperthermia treatment protocol. He was subsequently transferred to the
      surgical intensive care unit for continued management and had a favorable
      postoperative course. This case underscores the importance of awareness of
      malignant hyperthermia and its presentation. This condition carries a potential
      high risk of complications after exposure to triggering anesthetic agents. Taking
      a complete and detailed history may help to identify potential cases. In this
      case, it was subsequently discovered that the patient's biological sister had a
      nearly fatal reaction to general anesthesia several years before this incident.
      Intraoperative vigilance in the monitoring of vital signs cannot be
      overemphasized. An increase in end-tidal carbon dioxide values, in addition to
      other clinical signs that cannot be easily attributed to other causes, should
      increase the clinical index of suspicion for a diagnosis of malignant
      hyperthermia.

PMID- 30098955
TI  - Atypical Metastasis of p16-Positive Tonsillar Squamous Cell Carcinoma to the
      Pleura: A Case Report.
AB  - Incidence rates and patterns of distant metastases of head and neck malignancies
      are well documented in the literature, such that focused management strategies
      are routinely practiced in anticipation of their likely behavior. Head and neck
      tumors are known to most commonly metastasize to the lungs, skeletal system, and
      liver, generally within 2 years of definitive treatment and in the context of
      poor locoregional control of the primary lesion. Recent studies, however, have
      shown that human papillomavirus (HPV)-positive oropharyngeal squamous cell
      carcinoma (SCCa) tumors display different patterns of distant metastases than
      those traditionally described for head and neck HPV-negative SCCa tumors. This
      finding has substantial implications for how patients undergoing treatment of
      these cancers should be surveilled after therapy. This report describes a case of
      p16-positive tonsillar SCCa with metastasis to a highly unusual secondary site in
      the pleura to show an example of the unconventional patterns of distant
      metastases reported for HPV-positive oropharyngeal SCCa in the recent literature.
      We aim to provide a more thorough understanding of this case by discussing the
      pathogenesis of metastatic spread to the pleura and the clinical progression
      generally observed in patients with secondary pleural malignancy. This report
      goes on to investigate how behaviors of distant metastases exhibited by HPV
      positive oropharyngeal SCCa differ from those of more conventionally described
      head and neck HPV-negative SCCa and the implications thereof for strategies of
      post-treatment surveillance of these tumors going forward.

PMID- 30098952
TI  - Changing geographical patterns and trends in cancer incidence in children and
      adolescents in Europe, 1991-2010 (Automated Childhood Cancer Information System):
      a population-based study.
AB  - BACKGROUND: A deceleration in the increase in cancer incidence in children and
      adolescents has been reported in several national and regional studies in Europe.
      Based on a large database representing 1.3 billion person-years over the period
      1991-2010, we provide a consolidated report on cancer incidence trends at ages 0
      19 years. METHODS: We invited all population-based cancer registries operating in
      European countries to participate in this population-based registry study. We
      requested a listing of individual records of cancer cases, including sex, age,
      date of birth, date of cancer diagnosis, tumour sequence number, primary site,
      morphology, behaviour, and the most valid basis of diagnosis. We also requested
      population counts in each calendar year by sex and age for the registration area,
      from official national sources, and specific information about the covered area
      and registration practices. An eligible registry could become a contributor if it
      provided quality data for all complete calendar years in the period 1991-2010.
      Incidence rates and the average annual percentage change with 95% CIs were
      reported for all cancers and major diagnostic groups, by region and overall,
      separately for children (age 0-14 years) and adolescents (age 15-19 years). We
      examined and quantified the stability of the trends with joinpoint analyses.
      FINDINGS: For the years 1991-2010, 53 registries in 19 countries contributed a
      total of 180 335 unique cases. We excluded 15 162 (8.4%) of 180 335 cases due to
      differing practices of registration, and considered the quality indicators for
      the 165 173 cases included to be satisfactory. The average annual age
      standardised incidence was 137.5 (95% CI 136.7-138.3) per million person-years
      and incidence increased significantly by 0.54% (0.44-0.65) per year in children
      (age 0-14 years) with no change in trend. In adolescents, the combined European
      incidence was 176.2 (174.4-178.0) per million person-years based on all 35 138
      eligible cases and increased significantly by 0.96% (0.73-1.19) per year,
      although recent changes in rates among adolescents suggest a deceleration in this
      increasing trend. We observed temporal variations in trends by age group,
      geographical region, and diagnostic group. The combined age-standardised
      incidence of leukaemia based on 48 458 cases in children was 46.9 (46.5-47.3) per
      million person-years and increased significantly by 0.66% (0.48-0.84) per year.
      The average overall incidence of leukaemia in adolescents was 23.6 (22.9-24.3)
      per million person-years, based on 4702 cases, and the average annual change was
      0.93% (0.49-1.37). We also observed increasing incidence of lymphoma in
      adolescents (average annual change 1.04% [0.65-1.44], malignant CNS tumours in
      children (average annual change 0.49% [0.20-0.77]), and other tumours in both
      children (average annual change 0.56 [0.40-0.72]) and adolescents (average annual
      change 1.17 [0.82-1.53]). INTERPRETATION: Improvements in the diagnosis and
      registration of cancers over time could partly explain the observed increase in
      incidence, although some changes in underlying putative risk factors cannot be
      excluded. Cancer incidence trends in this young population require continued
      monitoring at an international level. FUNDING: Federal Ministry of Health of the
      Federal German Government, the European Union's Seventh Framework Programme, and
      International Agency for Research on Cancer.

PMID- 30098956
TI  - What Factors Are Associated With Regional Recurrence After Operative Treatment of
      Oral Squamous Cell Carcinoma?
AB  - PURPOSE: A considerable proportion of oral squamous cell carcinoma (OSCC)
      recurrences involve the neck, which has a substantial impact on prognosis and is
      poorly understood. The purpose of this study was to analyze clinical and
      pathologic characteristics of regional recurrence of OSCC and identify possible
      risk factors. MATERIALS AND METHODS: A single-center retrospective cohort study
      was designed to address the study purpose. All patients who were treated
      surgically for primary OSCC with or without adjuvant therapy between 2010 and
      2015 were considered for inclusion with respect to predefined criteria, and
      demographic, clinical, and pathologic variables were collected. The lymph node
      status after primary OSCC treatment (pN) was defined as the predictor variable,
      and the occurrence of regional recurrence served as the primary outcome variable.
      Further variables of special interest were the histologic differentiation (G
      status) of the primary OSCC and the values of the lymph node ratio and log odds
      of positive lymph nodes. Descriptive, inferential, and appropriate time-dependent
      (Kaplan-Meier analysis, Cox regression model) statistics were computed. The level
      of statistical significance was set at P <= .05. RESULTS: The study sample was
      composed of 171 patients (70 women and 101 men; average age, 62.4 years). Neck
      failure occurred in 18 patients (11%) either in combination with local recurrence
      (15 patients) or in isolation (3 patients). Poor histologic differentiation of
      the primary tumor was identified as an independent risk factor for regional
      recurrence. Most neck recurrences manifested in previously unaddressed levels (IV
      and V). CONCLUSIONS: Regional recurrence of OSCC might be associated with
      specific clinicopathologic parameters of the primary tumor. The importance of
      these parameters for OSCC prognosis assessment and recurrence prediction should
      be elucidated in further studies.

PMID- 30098957
TI  - Oral Cysticercosis: A Case Series and Review of Literature.
AB  - The cysticercus is the larval form of the pork tapeworm. Oral cavity involvement
      of cysticercosis is rare but frequently reported from developing countries. This
      report presents 3 cases of oral cysticercosis involving the tongue and buccal
      mucosa in isolation. All 3 patients were treated with surgical excision and had
      an uneventful postoperative course. A brief review of the PubMed English-language
      literature search is presented. Oral cavity involvement with cysticercosis
      presents a diagnostic dilemma. Management is primarily surgical and carries an
      excellent prognosis.

PMID- 30098958
TI  - Postoperative Alopecia Following Oral Surgery.
AB  - Postoperative alopecia is an uncommon complication and its outcome is an
      esthetically drastic change. Although its mechanism has not been clearly
      reported, risk factors might be positioning and prolonged operative time during
      oral surgeries. In addition, perioperative stressful conditions might influence
      the biological clock of the hair cycle. This report presents 2 cases of
      postoperative alopecia after oral surgery. Prevention of alopecia with type of
      headrest, change in head positioning, and avoidance of continuous compression is
      important.

PMID- 30098959
TI  - Combating Acute Heart Failure in the Arena: Lessons From the ROPA-DOP Trial.

PMID- 30098960
TI  - Vaccination Trends in Patients With Heart Failure: Insights From Get With The
      Guidelines-Heart Failure.
AB  - OBJECTIVES: This study sought to evaluate and contribute to the limited data on
      U.S. hospital practice patterns with respect to respiratory vaccination in
      patients hospitalized with heart failure (HF). BACKGROUND: Respiratory infection
      is a major driver of morbidity in patients with HF, and many influenza and
      pneumococcal infections may be prevented by vaccination. METHODS: This study
      evaluated patients hospitalized at centers participating in the Get With The
      Guidelines-HF (GWTG-HF) registry from October 2012 to March 2017. The proportion
      of patients receiving vaccination was described for influenza and pneumococcal
      vaccination, respectively. The association of hospital-level vaccination rates
      with individual GWTG-HF performance measures and defect-free care was evaluated
      using multivariable modeling. RESULTS: This study evaluated 313,761 patients
      discharged from 392 hospitals during the study period. The proportion of patients
      receiving influenza vaccination was 68% overall and declined from 70% in 2012 to
      2013 to 66% in 2016 to 2017 (p < 0.001), although this was not statistically
      significant after adjustment (odds ratio: 1.05 per flu season; 95% confidence
      interval [CI]: 0.94 to 1.18). The proportion of patients receiving pneumococcal
      vaccination was 66% overall and decreased over the study period from 71% in 2013
      to 60% in 2016 (p < 0.001), remaining significant after adjustment (odds ratio:
      0.75 per calendar year; 95% CI: 0.67 to 0.84). Hospitals with higher vaccination
      rates were more likely to discharge patients with higher performance on defect
      free care and individual GWTG-HF performance measures (p < 0.001). In a subset of
      patients with linked Medicare claims, vaccinated patients had similar rates of 1
      year all-cause mortality (adjusted hazard ratio: 0.96 [95% CI: 0.89 to 1.03] for
      influenza vaccination; adjusted hazard ratio: 0.95 [95% CI: 0.89 to 1.01] for
      pneumococcal vaccination) compared with those not vaccinated. CONCLUSIONS: Nearly
      1 in 3 patients hospitalized with HF at participating hospitals were not
      vaccinated for influenza or pneumococcal pneumonia, and vaccination rates did not
      improve from 2012 to 2017. Hospitals that exhibited higher vaccination rates
      performed well with respect to other HF quality of care measures. Vaccination
      status was not associated with differences in clinical outcomes. Further
      randomized controlled data are needed to assess the relationship between
      vaccination and outcomes.

PMID- 30098961
TI  - Long-Chain Omega-3 Fatty Acid Supplements in Depressed Heart Failure Patients:
      Results of the OCEAN Trial.
AB  - OBJECTIVES: The goal of this study was to test the effects of long-chain omega-3
      fatty acid supplementation on omega-3 levels, depressive symptoms, and other
      psychosocial factors, as well as other chronic heart failure (CHF)-related
      functional measures. BACKGROUND: Patients with CHF and depression had low blood
      omega-3 concentrations that were associated with an elevated risk of mortality.
      METHODS: This study was a randomized, double-blind, placebo-controlled pilot
      clinical trial using a 400/200 eicosapentaenoic acid (EPA)/docosahexaenoic acid
      (DHA) fish oil at 2 g and an almost pure EPA at 2 g, compared with a matched
      placebo, daily for 12 weeks for patients with CHF and major depressive disorder.
      Statistical analyses included the intention-to-treat population and "completers"
      (defined as participants consuming >=70% of the capsules and completing the final
      endpoint evaluation between 10 and 14 weeks). RESULTS: A total of 108 patients
      with CHF and major depressive disorder and a score >=18 on the Hamilton
      Depression Scale who were randomized at 1:1:1 to the 3 interventions at 3
      enrolling centers from June 12, 2014, to May 19, 2016; 80 (74.1%) qualified as
      completers. Intention-to-treat analyses revealed that the levels of all omega-3
      variables were significantly elevated in the omega-3 groups, whereas the placebo
      group showed little change; there were no between-group differences with overall
      depression measurements. Per-protocol exploratory analyses showed that scores on
      the social functioning measurement of the 36-item Short Form Health Survey
      improved notably in the 400/200 EPA/DHA (p = 0.040) and EPA (p = 0.10) groups
      compared with the placebo group. Spearman correlation analysis indicated that
      increased omega-3 indices were associated with improved cognitive depressive
      symptoms. CONCLUSIONS: Omega-3 supplementation resulted in significant increases
      in omega-3 levels in red blood cell counts, corresponding to a particular
      compound of omega-3. Changes in cognitive depressive symptoms and social function
      were in favor of the omega-3 supplementation. Further studies with larger sample
      sizes are necessary to confirm the benefits of omega-3 supplementation on
      modifying psychosocial factors for patients with CHF. (Omega-3 Supplementation
      for Co-Morbid Depression and Heart Failure Treatment [OCEAN]; NCT02057406).

PMID- 30098963
TI  - Vaccinations in Heart Failure: An Expert-Opinion Based Recommendation That
      Deserves Randomized Validation.

PMID- 30098962
TI  - Randomized Evaluation of Heart Failure With Preserved Ejection Fraction Patients
      With Acute Heart Failure and Dopamine: The ROPA-DOP Trial.
AB  - OBJECTIVES: This study sought to compare a continuous infusion diuretic strategy
      versus an intermittent bolus diuretic strategy, with the addition of low-dose
      dopamine (3 MUg/kg/min) in the treatment of hospitalized patients with heart
      failure with preserved ejection fraction (HFpEF). BACKGROUND: HFpEF patients are
      susceptible to development of worsening renal function (WRF) when hospitalized
      with acute heart failure; however, inpatient treatment strategies to achieve safe
      and effective diuresis in HFpEF patients have not been studied to date. METHODS:
      In a prospective, randomized, clinical trial, 90 HFpEF patients hospitalized with
      acute heart failure were randomized within 24 h of admission to 1 of 4
      treatments: 1) intravenous bolus furosemide administered every 12 h; 2)
      continuous infusion furosemide; 3) intermittent bolus furosemide with low-dose
      dopamine; and 4) continuous infusion furosemide with low-dose dopamine. The
      primary endpoint was percent change in creatinine from baseline to 72 h. Linear
      and logistic regression analyses with tests for interactions between diuretic and
      dopamine strategies were performed. RESULTS: Compared to intermittent bolus
      strategy, the continuous infusion strategy was associated with higher percent
      increase in creatinine (continuous infusion: 16.01%; 95% confidence interval
      [CI]: 8.58% to 23.45% vs. intermittent bolus: 4.62%; 95% CI: -1.15% to 10.39%; p
      = 0.02). Low-dose dopamine had no significant effect on percent change in
      creatinine (low-dose dopamine: 12.79%; 95% CI: 5.66% to 19.92%, vs. no-dopamine:
      8.03%; 95% CI: 1.44% to 14.62%; p = 0.33). Continuous infusion was also
      associated with greater risk of WRF than intermittent bolus (odds ratio [OR]:
      4.32; 95% CI: 1.26 to 14.74; p = 0.02); no differences in WRF risk were seen with
      low-dose dopamine. No significant interaction was seen between diuretic strategy
      and low-dose dopamine (p > 0.10). CONCLUSIONS: In HFpEF patients hospitalized
      with acute heart failure, low-dose dopamine had no significant impact on renal
      function, and a continuous infusion diuretic strategy was associated with renal
      impairment. (Diuretics and Dopamine in Heart Failure With Preserved Ejection
      Fraction [ROPA-DOP]; NCT01901809).

PMID- 30098964
TI  - Antihyperglycemic Therapies to Treat Patients With Heart Failure and Diabetes
      Mellitus.
AB  - There is increasing recognition of the relationship between diabetes and heart
      failure (HF). Comorbid diabetes is associated with worse outcomes in patients
      with HF, and death from HF forms a large burden of mortality among patients with
      diabetes and atherosclerotic cardiovascular disease. However, there is evidence
      of harm relating to the risk of HF outcomes from several antihyperglycemic
      therapies. The absence of well-powered randomized controlled studies has resulted
      in significant treatment variations in the glycemic management in patients with
      coexisting diabetes and HF. However, there is emerging evidence from recent
      clinical trials suggesting that sodium-glucose-co-transporter-2 inhibitors may be
      used as a therapy to improve HF outcomes. In order to understand the current
      state of knowledge, we reviewed the evolving evidence of antihyperglycemic
      therapies and present strategies to optimize these therapies in patients with
      diabetes and HF. This analysis is based on discussions among scientists, clinical
      trialists, industry sponsors, and regulatory representatives who attended the
      12th Global Cardiovascular Clinical Trialists Forum, Washington, DC, December 1
      to 3, 2016.

PMID- 30098965
TI  - Heart Failure With Improved Ejection Fraction: Is it Possible to Escape One's
      Past?
AB  - Among patients with heart failure with reduced ejection fraction, investigators
      have repeatedly identified a subgroup whose left ventricular ejection fraction
      and structural remodeling can improve to normal or nearly normal levels with or
      without medical therapy. This subgroup of patients with "heart failure with
      improved ejection fraction" has distinct clinical characteristics and a more
      favorable prognosis compared with patients who continue to have reduced ejection
      fraction. However, many of these patients also manifest clinical and biochemical
      signs of incomplete resolution of heart failure pathophysiology and remain at
      some risk of adverse outcomes, thus indicating that they may not have completely
      recovered. Although rigorous evidence on managing these patients is sparse, there
      are several reasons to recommend continuation of heart failure therapies,
      including device therapies, to prevent clinical deterioration. Notable exceptions
      to this recommendation may include patients who recover from peripartum
      cardiomyopathy, fulminant myocarditis, or stress cardiomyopathy, whose excellent
      long-term prognoses may imply true myocardial recovery. More research on these
      patients is needed to better understand the mechanisms that lead to improvement
      in ejection fraction and to guide their clinical management.

PMID- 30098966
TI  - Predictors of Hospice Enrollment for Patients With Advanced Heart Failure and
      Effects on Health Care Use.
AB  - OBJECTIVES: This study sought to: 1) identify the predictors of hospice
      enrollment for patients with heart failure (HF); and 2) determine the impact of
      hospice enrollment on health care use. BACKGROUND: Patients with HF rarely enroll
      in hospice. Little is known about how hospice affects this group's health care
      use. METHODS: Using a propensity score-matched sample of Medicare decedents with
      >=2 HF discharges within 6 months, an Outcome and Assessment Information Set
      (OASIS) assessment, and subsequent death, we used Medicare administrative,
      claims, and patient assessment data to compare hospitalizations, intensive care
      unit stays, and emergency department visits for those beneficiaries who enrolled
      in hospice and those who did not. RESULTS: The propensity score-matched sample
      included 3,067 beneficiaries in each group with a mean age of 82 years; 53% were
      female, and 15% were Black, Asian, or Hispanic. For objective 1, there were no
      differences in the characteristics, symptom burden, or functional status between
      groups that were associated with hospice enrollment. For objective 2, in the 6
      months after the second HF discharge, the hospice group had significantly fewer
      emergency department visits (2.64 vs. 2.82; p = 0.04), hospital days (3.90 vs.
      4.67; p < 0.001), and intensive care unit stays (1.25 vs. 1.51; p < 0.001); they
      were less likely to die in the hospital (3% vs. 56%; p < 0.001), and they had
      longer median survival (80 days vs. 71 days; log-rank test p = 0.004).
      CONCLUSIONS: Beneficiaries' characteristics, including symptom burden and
      functional status, do not predict hospice enrollment. Those patients who enrolled
      in hospice used less health care, survived longer, and were less likely to die in
      the hospital. A tailored hospice model may be needed to increase enrollment and
      offer benefits to patients with HF.

PMID- 30098967
TI  - A Bayesian Model to Predict Survival After Left Ventricular Assist Device
      Implantation.
AB  - OBJECTIVES: This study investigates the use of a Bayesian statistical models to
      predict survival at various time points in patients undergoing left ventricular
      assist device (LVAD) implantation. BACKGROUND: LVADs are being increasingly used
      in patients with end-stage heart failure. Appropriate patient selection continues
      to be key in optimizing post-LVAD outcomes. METHODS: Data used for this study
      were derived from 10,277 adult patients from the INTERMACS (Inter-Agency Registry
      for Mechanically Assisted Circulatory Support) who had a primary LVAD implanted
      between January 2012 and December 2015. Risk for mortality was calculated
      retrospectively for various time points (1, 3, and 12 months) after LVAD
      implantation, using multiple pre-implantation variables. For each of these
      endpoints, a separate tree-augmented naive Bayes model was constructed using the
      most predictive variables. RESULTS: A set of 29, 26, and 31 pre-LVAD variables
      were found to be predictive at 1, 3, and 12 months, respectively. Predictors of 1
      month mortality included low Inter-Agency Registry for Mechanically Assisted
      Circulatory Support profile, number of acute events in the 48 h before surgery,
      temporary mechanical circulatory support, and renal and hepatic dysfunction.
      Variables predicting 12-month mortality included advanced age, frailty, device
      strategy, and chronic renal disease. The accuracy of all Bayesian models was
      between 76% and 87%, with an area under the receiver operative characteristics
      curve of between 0.70 and 0.71. CONCLUSIONS: A Bayesian prognostic model for
      predicting survival based on the comprehensive INTERMACS registry provided highly
      accurate predictions of mortality based on pre-operative variables. These models
      may facilitate clinical decision-making while screening candidates for LVAD
      therapy.

PMID- 30098968
TI  - Cardiac Resynchronization Therapy in Inotrope-Dependent Heart Failure Patients: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVES: The purpose of this study was to evaluate outcomes after cardiac
      resynchronization therapy (CRT) in inotrope-dependent patients with heart failure
      (HF) to ascertain the viability of CRT in these patients. BACKGROUND: During the
      last decade, significant numbers of trials have demonstrated the beneficial
      effect of CRT in the treatment of patients with HF and systolic dysfunction,
      prolonged QRS complex duration, and New York Heart Association functional class
      III or IV. However, it is currently undetermined whether CRT may benefit patients
      who require inotropic support. METHODS: The authors systematically searched
      Medline, Embase, Scopus, and the Cochrane Library through March 2017 for studies
      evaluating outcomes after CRT in inotrope-dependent patients with HF. The study
      analyzed 8 studies including 151 patients. Most of the patients were in New York
      Heart Association functional class IV (80.1%), and all had severe systolic HF,
      with a left ventricular ejection fraction <30% and a significant intraventricular
      conduction delay in their surface electrocardiogram (QRS complex duration >130
      ms). RESULTS: The pooled analysis demonstrated that 93% of the reported patients
      (95% confidence interval: 86% to 100%) were weaned from inotropic support after
      CRT, and the overall 12-month survival rate was 69% (95% confidence interval: 56%
      to 83%). CONCLUSIONS: This study suggests that rescue CRT may be considered a
      viable therapeutic option in inotrope-dependent patients with HF. In these
      patients, rescue CRT may allow them to be weaned from inotropic therapy, improve
      their quality of life, and decrease the rate of mortality; furthermore, rescue
      CRT may serve as a possible bridge to cardiac transplantation or left ventricular
      assist device therapy.

PMID- 30098969
TI  - Predicting Prognosis in Heart Failure: Important, But Easier Said Than Done.

PMID- 30098970
TI  - INTERMACS Profiles and Outcomes Among Non-Inotrope-Dependent Outpatients With
      Heart Failure and Reduced Ejection Fraction.
AB  - OBJECTIVES: This study sought to evaluate INTERMACS (Interagency Registry for
      Mechanically Assisted Circulatory Support) profiles for prognostic use among
      ambulatory non-inotrope-dependent patients with heart failure with reduced
      ejection fraction (HFrEF). BACKGROUND: Data for INTERMACS profiles and prognoses
      in ambulatory patients with HFrEF are limited. METHODS: We evaluated 3-year
      outcomes in 969 non-inotrope-dependent outpatients with HFrEF (EF: <=40%) not
      previously receiving advanced HF therapies. Patients meeting an INTERMACS profile
      at baseline were classified as profile 7 (n = 348 [34.7%]); 146 patients (14.5%)
      were classified profile 6; and 52 patients (5.2%) were classified profile 4 to 5.
      Remaining patients were classified "stable Stage C" (n = 423 [42.1%]). RESULTS:
      Three-year mortality rate was 10.0% among stable Stage C patients compared with
      21.8% among INTERMACS profile 7 (hazard ratio [HR] vs. Stage C: 2.45; 95%
      confidence interval [CI]: 1.64 to 3.66), 26.0% among profile 6 (HR: 3.93; 95% CI:
      1.64 to 3.66), and 43.8% among profile 4 to 5 (HR: 6.35; 95% CI: 3.51 to 11.5)
      patients. Hospitalization rates for HF were 4-fold higher among INTERMACS profile
      7 (38 per 100 patient-years; rate ratio [RR] vs. Stage C: 3.88; 95% CI: 2.70 to
      5.35), 6-fold higher among profile 6 patients (54 per 100 patient-years; RR:
      5.69; 95% CI: 3.72 to 8.71), and 10-fold higher among profile 4 to 5 patients (69
      per 100 patient-years; RR: 9.96; 95% CI: 5.15 to 19.3) than stable Stage C
      patients (11 per 100 patient-years). All-cause hospitalization rates had similar
      trends. INTERMACS profiles offered better prognostic separation than NYHA
      functional classifications. CONCLUSIONS: INTERMACS profiles strongly predict
      subsequent mortality and hospitalization burden in non-inotrope-dependent
      outpatients with HFrEF. These simple profiles could therefore facilitate and
      promote advanced HF awareness among clinicians and planning for advanced HF
      therapies.

PMID- 30098971
TI  - It Is Time to Discuss Dying.

PMID- 30098972
TI  - The Australian high performance and sport science workforce: A national profile.
AB  - OBJECTIVES: The purpose of this study was to provide a profile of the
      demographics and employment characteristics of the Australian high performance
      and sport science workforce. DESIGN: This study used a cross-sectional,
      quantitative survey methodology to collect data about the Australian high
      performance and sport science workforce. METHOD: 175 Australian high performance
      and sport science employees completed an online survey which captured demographic
      information and work-related characteristics such as role, industry sector,
      income, permanence of employment and hours worked. Descriptive statistics were
      used to summarise information and some comparisons were made between position
      titles, industry sectors and sexes. RESULTS: The Australian high performance and
      sport science workforce is predominantly male (76.0%), <=35 years of age (50.3%),
      located on the eastern seaboard of Australia (69%) and have been in their current
      position for 2-5 years (37.4%). They are mostly employed on a fixed term contract
      of 2.4 years, by an institute of sport. Income varied, with those working in
      professional sporting clubs and/or employed as high performance managers earning
      the highest wage. On average, participants worked well over their contracted
      hours, with a considerable proportion of these hours outside the standard 9-5
      working week. CONCLUSIONS: Employees in the high performance and sport science
      workforce in Australia face significant professional issues that relate to long
      and unusual work hours, job insecurity and income disparity. Policy makers and
      the managers of this workforce should consider the impact of these issues on work
      life balance, staff retention rates and the risk of burnout.

PMID- 30098973
TI  - Urinary incontinence and disordered eating in female elite athletes.
AB  - OBJECTIVES: To evaluate the association between urinary incontinence and
      disordered eating, in elite female athletes. DESIGN: This cross-sectional study
      included 744 young and healthy Portuguese women: 372 elite athletes and 372 age
      matched non-athletes, mean age 21+/-5.3years. METHODS: Data regarding clinical,
      demographic, and sport practice characteristics were collected by questionnaire.
      The International Consultation on Incontinence Questionnaire-Urinary Incontinence
      Short Form was applied to identify urinary incontinence. The Eating Disorder
      Examination Questionnaire was applied to identify disordered eating. Odds ratios
      with 95% confidence intervals (95% CI) were used to estimate the association
      between UI and disordered eating. RESULTS: The prevalence of urinary incontinence
      in athletes and non-athletes was 29.3% and 13.4%, p<0.001, respectively. No
      difference in prevalence of disordered eating was found between athletes (17.7%)
      and non-athletes (20.2%), p=0.435. Urinary incontinence was associated with
      disordered eating only in the athletes. After adjustment for age, type of sport,
      smoking and alcohol intake, athletes with disordered eating presented increased
      odds of urinary incontinence of any type over athletes without disordered eating
      (OR=3.09; 95% CI: 1.74-5.50). CONCLUSIONS: Athletes with disordered eating were
      three times more likely to present urinary incontinence than women without
      disordered eating. There is a need for further studies to elaborate on mechanisms
      for this association.

PMID- 30098974
TI  - Temporal trends in muscular fitness of English 10-year-olds 1998-2014: An
      allometric approach.
AB  - OBJECTIVES: To identify temporal trends in muscular fitness of English children
      using allometric scaling for height and weight to adjust for the influence of
      body size. DESIGN: Repeated cross-sectional study. METHODS: We measured; height,
      weight, standing broad-jump, handgrip, sit-ups and bent-arm hang in 10-year-old
      boys and girls from Chelmsford, England in: 2014 (n=306), 2008 (n=304) and 1998
      (n=310). Physical activity was (PAQ-C) was assessed in 2008 and 2014. Muscular
      fitness was allometrically scaled for height and weight. We assessed temporal
      trends using General Linear Models (fixed factors: wave and sex) and reported
      effect sizes using partial eta squared (etaP2). We compared percentage change per
      year 1998-2008 with 2008-2014. RESULTS: Ten-year-olds in 2014 were taller and
      heavier than in 2008 and 1998 but there were no differences in BMI. Compared with
      2008, physical activity was lower in boys (etaP2=0.012) and girls (etaP2=0.27)
      assessed in 2014. There were significant main effects of wave for handgrip
      (etaP2=0.060), sit-ups (etaP2=0.120) and bent-arm hang (etaP2=0.204). Pairwise
      comparisons showed muscular fitness of both sexes was significantly lower in 2014
      than in 1998. From 2008 to 2014 percent change per year in handgrip (1.6%) and
      sit-ups (3.9%) were greater than for the preceding decade (handgrip 0.6%, sit-ups
      2.6%). CONCLUSIONS: Downward temporal trends in muscular fitness appear
      independent of secular changes in body size. We found a decrease in self-reported
      physical activity concurrent with the accelerated declines in fitness from 2008
      to 2014. These findings suggest the declines in children are not engaging in
      physical activities which support development of muscular fitness.

PMID- 30098975
TI  - Quantification of Achilles and patellar tendon structure on imaging does not
      enhance ability to predict self-reported symptoms beyond grey-scale ultrasound
      and previous history.
AB  - BACKGROUND: Tendon pathology on imaging has been associated with an increased
      risk of developing symptoms. This evidence is based on classifying the tendon as
      normal or pathological. It is unclear whether the extent of tendon pathology is
      associated with the development or severity of symptoms. OBJECTIVES: To
      investigate whether the presence and extent of tendon pathology on ultrasound
      tissue characterisation (UTC), or a previous history of symptoms, were associated
      with the development of symptoms over a football season. METHODS: 179 male
      Australian football players underwent UTC imaging of their Achilles and/or
      patellar tendon at the start of the pre-season. Players completed monthly OSTRC
      overuse questionnaires to quantify the presence and severity of Achilles and/or
      patellar tendon symptoms. Risk factor analysis was performed to identify
      associations between imaging and the development of symptoms. RESULTS: A
      pathological Achilles tendon increased the risk of developing symptoms (RR=3.2,
      95%CI 1.7-5.9). Conversely, a pathological patellar tendon was not significantly
      associated with the development of symptoms (RR=1.8, 95%CI 0.9-3.7).
      Quantification of tendon structure using UTC did not enhance the ability to
      identify athletes who developed symptoms. Previous history of symptoms was the
      strongest predictor for the development of symptoms (Achilles RR=3.0 95%CI 1.8
      4.8; patellar RR=3.7 95%CI 2.2-6.1). CONCLUSION: Tendon pathology was associated
      with the development of self-reported symptoms; however previous history of
      symptoms was a stronger risk factor. The extent of disorganisation quantified by
      UTC should not be used as a marker for the presence or severity of current and
      future symptoms.

PMID- 30098976
TI  - Longitudinal associations of fundamental movement skills with objectively
      measured physical activity and sedentariness during school transition from
      primary to lower secondary school.
AB  - OBJECTIVES: This study aimed to investigate cross-lagged associations of leaping
      skill and throwing-catching skills with objectively measured moderate-to-vigorous
      physical activity (MVPA) and sedentary time (ST) during school transition from
      upper primary (Grade 6) to lower secondary school (Grade 7). DESIGN: This study
      is a one-year prospective follow-up study within Finnish school settings.
      Students' MVPA, ST, leaping skill and throwing-catching skills were measured at
      Grade 6 and subsequently at Grade 7. METHODS: A sample of 336 students (163
      girls, 173 boys; M age=12.0 years, SD=0.4 at Grade 6 participated in the study.
      Students' MVPA and ST were measured objectively by hip-worn accelerometers.
      Leaping skill was measured by 5-leaps test. Throwing and catching skills were
      measured by throwing-catching combination test. Cross-lagged structural equation
      modeling was conducted to evaluate the associations between MVPA, ST, leaping
      skill, and throwing-catching skills at Grade 6 and Grade 7. RESULTS: Results
      demonstrated three significant cross-lagged associations among girls: (1) leaping
      skill measured at Grade 6 was negatively associated with ST at Grade 7; (2)
      objectively measured MVPA at Grade 6 associated positively with leaping skill at
      Grade 7; and (3) throwing-catching skills measured at Grade 6 associated
      positively with leaping skill measured at Grade 7. There were no statistically
      significant cross-lagged associations between the study variables for the sample
      of boys. CONCLUSIONS: The results of this study indicated that supporting
      opportunities for girls' engagement in both MVPA and leaping skill development
      activities during their primary school education is strongly recommended.

PMID- 30098978
TI  - The association of teaching-learning methods and self-confidence of nurse
      midwives. A survey from one province in India.
AB  - BACKGROUND: This study aimed to investigate the association between self
      confidence of final-year students in selected midwifery skills and teaching
      learning methods used in the two formally recognized education programs for nurse
      midwives in India. DESIGN: A cross-sectional survey PARTICIPANTS: 633 final-year
      students, from 25 educational institutions randomly selected, stratified by type
      of program (diploma/bachelor), and ownership (private/government) in Gujarat.
      DATA COLLECTION AND ANALYSIS: Students assessed their confidence on a 4-point
      scale, in four midwifery competency domains-antepartum, intrapartum, postpartum,
      and newborn care recommended by the International Confederation of Midwives
      (ICM). Explorative factor analysis was used to reduce skill statements into
      subscales separately for each domain. Odds ratios with 95% CI were calculated for
      students with high confidence (>=75th percentile on each subscale) and not high
      confidence (all others) between diploma and bachelor students. RESULTS: Classroom
      teaching was the most practiced method. 'Laboratory demonstrations', 'Practice on
      models', 'Demonstrations at clinical sites', 'Births Attended' (Hands-on clinical
      practice), and 'Satisfaction with clinical supervision' were practiced less,
      lesser in the bachelor's compared to the diploma program. High confidence was
      associated with 'Births Attended' (Hands-on clinical practice), 'Practice on
      models', and 'Satisfaction with clinical supervision' for all subscales of all
      four domains of competencies. CONCLUSIONS: Hands on skills practice in the
      laboratory and supervised clinical practice during clinical placements were
      associated with high confidence for basic clinical midwifery skills amongst
      students. The diploma program followed better pedagogoical approaches than the
      bachelor's program.

PMID- 30098977
TI  - Over- and underestimation of motor ability after a stroke: Implications for
      anosognosia.
AB  - We administered a discrepancy-based measure of anosognosia for hemiplegia (AHP)
      to a group of 42 right-brain-damaged (RBD) and left-brain-damaged (LBD) stroke
      patients with varying levels of functional motor ability. In addition to the
      expected (anosognosic) pattern of overestimation of motor function in some RBD
      patients, we found an equal and opposite underestimation in some others, both RBD
      and LBD. We also found that around a quarter of self-estimation error could be
      predicted directly from actual ability, such that patients with poorer motor
      function tended to overestimate, and vice versa. This pattern suggests that some
      misestimation is attributable simply to statistical regression. However, even
      after adjusting for this regression effect, levels of overestimation were
      significantly greater in RBD patients, while LBD patients were more likely to
      underestimate their motor ability.

PMID- 30098979
TI  - Australian caregivers' perceptions of influenza vaccination in pregnancy: A mixed
      methods exploration.
AB  - BACKGROUND: Pregnant women and their unborn children are at high risk from both
      pandemic and seasonal influenza. AIM: To explore views about influenza
      vaccination during pregnancy, in a pandemic and immediate post-pandemic context,
      among mothers and other carers of young children. METHODS: In a mixed methods
      study, caregivers from 16 childcare centres in Sydney, Australia, were surveyed
      in November and December 2009, and interviews were conducted with caregivers from
      six childcare centres between June 2009 and May 2011. FINDINGS: Emerging themes
      from 41 interviews conducted with mothers included: 'pregnancy as a protected
      state', 'risk negotiation' and 'centrality of healthcare worker interaction'. Of
      972 surveys distributed, 431 were completed (a response rate of 44%). Respondents
      perceived pandemic influenza risks to be greater for pregnant women than for
      their unborn children. Only 2% (9/383) of women reported being vaccinated against
      swine flu during pregnancy and 45% (168/383) indicated intent to receive swine
      flu vaccination in a future pregnancy. DISCUSSION: The low rates of maternal
      influenza vaccination revealed in this study contrast to recent gains in vaccine
      uptake. Vaccination decision-making in pregnancy can be complex and contextually
      driven for some women. Healthcare workers, including midwives, have a key role in
      addressing women's concerns about maternal influenza vaccination in both pandemic
      and interpandemic periods. CONCLUSIONS: Policy makers need to be cognisant of
      women's concerns and develop resources for both pregnant women and healthcare
      workers as part of both future pandemic planning and seasonal vaccination
      efforts.

PMID- 30098980
TI  - The uptake and implementation of the Baby Friendly Health Initiative in
      Australia.
AB  - PROBLEM: Despite evidence that implementation of the Initiative has been
      effective in increasing breastfeeding rates and duration of breastfeeding
      worldwide; the uptake is low with only 70 Baby Friendly accredited maternity
      facilities across Australia (approximately 23% of facilities). BACKGROUND: The
      Ten Steps to Successful Breastfeeding and International Code of Marketing of
      Breastmilk Substitutes shaped the foundation for the Initiative to implement
      practices that protect, promote and support breastfeeding. There is evidence that
      implementation of the Initiative is impacted by individual and organisational
      culture, organisational support, and education. Organisational change is also
      identified as playing an important role in the successful implementation of the
      Initiative. Despite policy and guideline support for the Initiative at national
      and state levels in Australia the uptake of the Initiative is low. AIM: The aim
      of this research was to explore health practitioners' perspectives about the
      uptake and implementation of the Initiative in Australia. METHODS: Semi
      structured, face-to-face, telephone and Skype interviews were conducted with 12
      health practitioners. Thematic analysis was used to analyse data. RESULTS:
      Participants identified that the uptake and implementation of the Initiative in
      Australia is complex. This complexity was related to six themes: (1) policy and
      guideline support for the Initiative, (2) leadership support to implement the
      Initiative, (3) improving breastfeeding and Initiative-related knowledge, (4)
      improving communication between stakeholders regarding the Initiative, (5)
      accreditation and reaccreditation processes, and (6) implementation complexity.
      CONCLUSION: Using organisational change theories as a guide to implementation of
      the Initiative may be useful for facilities intending to become accredited.

PMID- 30098981
TI  - Correction.

PMID- 30098982
TI  - Impact of Prior Local Treatment on the Outcomes of Metastatic Hormone-Sensitive
      Prostate Cancer: Secondary Analysis of a Randomized Controlled Trial.
AB  - BACKGROUND: Local treatment of metastatic prostate cancer and its impact on
      future disease course requires further assessment. We sought to evaluate the
      impact of prior local treatment to the prostate on the outcomes of hormone
      sensitive prostate cancer (HSPC) patients recruited in the CHAARTED study.
      PATIENTS AND METHODS: We performed a retrospective analysis of the prospectively
      collected data among patients with metastatic HSPC in the CHAARTED study, a phase
      3 multicenter study conducted between 2006 and 2014. The CHAARTED study compared
      androgen deprivation therapy plus docetaxel versus androgen deprivation therapy
      alone among patients with metastatic HSPC. The main outcomes of the current
      analysis are overall survival, progression-free survival, prostate cancer
      specific survival, and time to castration-resistant disease as assessed by Kaplan
      Meier analysis, log-rank testing, and Cox regression models. RESULTS: Kaplan
      Meier overall survival estimates were produced according to whether patients
      underwent prior local treatment and results were stratified by treatment arm. For
      both treatment arms, patients with prior local treatment had better overall
      survival (P < .01). Similarly, Kaplan-Meier progression-free survival estimates
      were produced according to whether patients underwent prior local treatment, and
      results were stratified by the treatment arm. For both treatment arms, patients
      with prior local treatment had better progression-free survival (P < .01). In an
      adjusted Cox multivariate model (adjusted for assigned study treatment arm, age,
      baseline prostate-specific antigen, and baseline Gleason score, volume of the
      disease (low risk or high risk) and baseline performance status), patients with
      prior local treatment had better overall survival (P = .045), progression-free
      survival (P = .035), and cancer-specific survival (P = .010) compared to those
      without prior local treatment. Moreover, they had a longer time to development of
      castration-resistant disease (P = .025). CONCLUSION: Patients with metastatic
      HSPC and prior local treatment had better overall, progression-free, and cancer
      specific survivals compared to those without prior local treatment. The impact of
      these findings on the treatment paradigms for metastatic HSPC should be
      thoroughly evaluated.

PMID- 30098985
TI  - SMFM Statement on Elective Induction of Labor in Low-Risk Nulliparous Women at
      Term: The ARRIVE Trial.

PMID- 30098983
TI  - Decarbamoylation of acetylcholinesterases is markedly slowed as carbamoyl groups
      increase in size.
AB  - Carbamates are esters of substituted carbamic acids that react with
      acetylcholinesterase (AChE) by initially transferring the carbamoyl group to a
      serine residue in the enzyme active site accompanied by loss of the carbamate
      leaving group followed by hydrolysis of the carbamoyl enzyme. This hydrolysis, or
      decarbamoylation, is relatively slow, and half-lives of carbamoylated AChEs range
      from 4 min to more than 30 days. Therefore, carbamates are effective AChE
      inhibitors that have been developed as insecticides and as therapeutic agents. We
      show here, in contrast to a previous report, that decarbamoylation rate constants
      are independent of the leaving group for a series of carbamates with the same
      carbamoyl group. When the alkyl substituents on the carbamoyl group increased in
      size from N-monomethyl- to N,N-dimethyl-, N-ethyl-N-methyl-, or N,N-diethyl-, the
      decarbamoylation rate constants decreased by 4-, 70-, and 800-fold, respectively.
      We suggest that this relationship arises as a result of active site distortion,
      particularly in the acyl pocket of the active site. Furthermore, solvent
      deuterium oxide isotope effects for decarbamoylation decreased from 2.8 for N
      monomethylcarbamoyl AChE to 1.1 for N,N-diethylcarbamoyl AChE, indicating a shift
      in the rate-limiting step from general acid-base catalysis to a likely
      conformational change in the distorted active site.

PMID- 30098984
TI  - Lipid metabolism alterations in the neuronal response to A53T alpha-synuclein and
      Fe-induced injury.
AB  - Pathological alpha-synuclein (alpha-syn) overexpression and iron (Fe)-induced
      oxidative stress (OS) are involved in the death of dopaminergic neurons in
      Parkinson's disease (PD). We have previously characterized the role of
      triacylglycerol (TAG) formation in the neuronal response to Fe-induced OS. In
      this work we characterize the role of the alpha-syn variant A53T during Fe
      induced injury and investigate whether lipid metabolism has implications for
      neuronal fate. To this end, we used the N27 dopaminergic neuronal cell line
      either untransfected (UT) or stably transfected with pcDNA3 vector (as a
      transfection control) or pcDNA-A53T-alpha-syn (A53T alpha-syn). The
      overexpression of A53T alpha-syn triggered an increase in TAG content mainly due
      to the activation of Acyl-CoA synthetase. Since fatty acid (FA) beta-oxidation
      and phospholipid content did not change in A53T alpha-syn cells, the unique
      consequence of the increase in FA-CoA derivatives was their acylation in TAG
      moieties. Control cells exposed to Fe-induced injury displayed increased OS
      markers and TAG content. Intriguingly, Fe exposure in A53T alpha-syn cells
      promoted a decrease in OS markers accompanied by alpha-syn aggregation and
      elevated TAG content. We report here new evidence of a differential role played
      by A53T alpha-syn in neuronal lipid metabolism as related to the neuronal
      response to OS.

PMID- 30098986
TI  - Do 5alpha-Reductase Inhibitors Raise Circulating Serum Testosterone Levels? A
      Comprehensive Review and Meta-Analysis to Explaining Paradoxical Results.
AB  - INTRODUCTION: Many studies have reported that 5alpha-reductase inhibitors
      (finasteride and dutasteride) raise serum testosterone (T) levels, yet there is
      lack of consistency among studies on this point. AIM: To review and meta-analyze
      available studies reporting changes in serum T concentrations in men treated with
      5alpha-reductase inhibitors (5alpha-RIs). METHODS: A Medline search using PubMed
      and EMBASE was performed including the following key words: "finasteride,"
      "dutasteride," "testosterone and 5alpha-reductases." MAIN OUTCOME MEASURE:
      Relevant studies were extracted, evaluated, and analyzed. Of these, 40 studies
      were analyzed qualitatively and 11 were included in the meta-analysis. A random
      effects model was used to conduct the meta-analysis. RESULTS: In 11 studies
      comprising 1,784 patients with age ranging between 18 and 83 years and average
      treatment follow-up of 17 months, meta-analytic estimate of the mean baseline
      change was 27 (95% confidence interval 1-54). The meta-analysis did not
      demonstrate unequivocal significant increase in serum T levels. The increase was
      not uniform among all studies reported. Sensitivity analysis showed that no
      single study contributed decisively to the outcome or could be attributed to drug
      action. The reported increases in T levels with finasteride or dutasteride in men
      with low baseline serum T may be attributed, in part, to increased trapping of T
      by unsaturated sex hormone binding globulin (SHBG) due to dissociation of 5alpha
      dihydrotestosterone. In men with high baseline T levels, there appears to be no
      change in serum T levels. 10 studies reported luteinizing hormone, follicle
      stimulating hormone, SHBG, and estradiol values and none reported significant
      changes in their levels, suggesting that observed changes in serum T levels are
      unlikely mediated by gonadotropins levels or peripheral conversion of T to
      estradiol. CONCLUSION: 5alpha-RI therapy is not associated with consistent and
      significant increases in serum T levels. Traish AM, Krakowsky Y, Doros G, et al.
      Do 5alpha-reductase inhibitors raise circulating serum testosterone levels? A
      comprehensive review and meta-analysis to explaining paradoxical results. Sex Med
      Rev 2018;XX:XXX-XXX.

PMID- 30098987
TI  - Inhibition of ERK-Drp1 signaling and mitochondria fragmentation alleviates IGF
      IIR-induced mitochondria dysfunction during heart failure.
AB  - Mitochondrial dysfunction is a major contributor to myocyte loss and the
      development of heart failure. Myocytes have quality control mechanisms to retain
      functional mitochondria by removing damaged mitochondria via specialized
      autophagy, i.e., mitophagy. The underlying mechanisms of fission affect the
      survival of cardiomyocytes, and left ventricular function in the heart is poorly
      understood. Here, we demonstrated the direct effect and potential mechanisms of
      mitochondrial functional defects associated with abnormal mitochondrial dynamics
      in heart failure. We observed that IGF-IIR signaling produced significant changes
      in mitochondrial morphology and function; such changes were associated with the
      altered expression and distribution of dynamin-related protein (Drp1) and
      mitofusin (Mfn2). IGF-IIR signaled extracellular signal-regulated kinase (ERK)
      activation to promote Drp1 phosphorylation and translocation to mitochondria for
      mitochondrial fission and mitochondrial dysfunction. Moreover, IGF-IIR signaling
      triggered Rab9-dependent autophagosome formation by the JNK-mediated
      phosphorylation of Bcl-2 at serine 87 and promoted ULK1/Beclin 1-dependent
      autophagic membrane formation. Excessive mitochondrial fission by Drp1 enhanced
      the Rab9-dependent autophagosome recognition and engulfing of damaged
      mitochondria and eventually decreased cardiomyocyte viability. Therefore, these
      results demonstrated the connection between Rab9-dependent autophagosomes and
      mitochondrial fission in cardiac myocytes, which provides a potential therapeutic
      strategy for treating heart disease.

PMID- 30098988
TI  - Protease-activated receptor 1 activation enhances doxorubicin-induced
      cardiotoxicity.
AB  - OBJECTIVE: The anti-cancer anthracycline drug Doxorubicin (Dox) causes
      cardiotoxicity. We investigated the role of protease-activated receptor 1 (PAR-1)
      in Dox-induced cardiotoxicity. METHODS AND RESULTS: In vitro experiments revealed
      that PAR-1 enhanced Dox-induced mitochondrial dysfunction, reactive oxygen
      species and cell death of cardiac myocytes and cardiac fibroblasts. The
      contribution of PAR-1 to Dox-induced cardiotoxicity was investigated by
      subjecting PAR-1-/- mice and PAR-1+/+ mice to acute and chronic exposure to Dox.
      Heart function was measured by echocardiography. PAR-1-/- mice exhibited
      significant less cardiac injury and dysfunction compared to PAR-1+/+ mice after
      acute and chronic Dox administration. PAR-1-/- mice had reduced levels of
      nitrotyrosine, apoptosis and inflammation in their heart compared to PAR-1+/+
      mice. Furthermore, inhibition of PAR-1 in wild-type mice with vorapaxar
      significantly reduced the acute Dox-induced cardiotoxicity. CONCLUSION: Our
      results indicate that activation of PAR-1 contributes to Dox-induced
      cardiotoxicity. Inhibition of PAR-1 may be a new approach to reduce Dox-induced
      cardiotoxicity in cancer patients.

PMID- 30098990
TI  - Neural correlates of action: Comparing meta-analyses of imagery, observation, and
      execution.
AB  - Several models propose Motor Imagery, Action Observation, and Movement Execution
      recruit the same brain regions. There is, however, no quantitative synthesis of
      the literature that directly compares their respective networks. Here we
      summarized data from neuroimaging experiments examining Motor Imagery (303
      experiments, 4902 participants), Action Observation (595 experiments, 11,032
      participants), and related control tasks involving Movement Execution (142
      experiments, 2302 participants). Comparisons across these networks showed that
      Motor Imagery and Action Observation recruited similar premotor-parietal cortical
      networks. However, while Motor Imagery recruited a similar subcortical network to
      Movement Execution, Action Observation did not consistently recruit any
      subcortical areas. These data quantify and amend previous models of the
      similarities in the networks for Motor Imagery, Action Observation, and Movement
      Execution, while highlighting key differences in their recruitment of motor
      cortex, parietal cortex, and subcortical structures.

PMID- 30098991
TI  - Preparation of Ibuprofen Microparticles by Antisolvent Precipitation
      Crystallization Technique: Characterization, Formulation, and In Vitro
      Performance.
AB  - This study demonstrates the preparation and characterization of ibuprofen (IBP)
      microparticles with some excipients by a controlled crystallization technique
      with improved dissolution performance. Using the optimum concentrations pluronic
      F127, hydroxypropyl methyl cellulose, D-mannitol, and l-leucine in aqueous
      ethanol, the IBP microparticles were prepared. The dissolution tests were
      performed in phosphate buffer saline using a United States Pharmacopoeia
      dissolution tester at 37 degrees C. The Raman spectroscopy was used to
      investigate the interactions and distribution of the IBP with the additives in
      the microcrystals. The prepared IBP microparticles showed higher dissolution
      compared to that of the smaller sized original IBP particles. The Raman data
      revealed that the excipients with a large number of hydroxyl groups distributed
      around the IBP particle in the crystal enhanced the dissolution of the drug by
      increasing the drug-solvent interaction presumably through hydrogen bonding. The
      Raman mapping technique gave an insight into the enhanced dissolution behavior of
      the prepared IBP microparticles, and such information will be useful for
      developing pharmaceutical formulations of hydrophobic drugs. The controlled
      crystallization was a useful technique to prepare complex crystals of IBP
      microparticles along with other additives to achieve the enhanced dissolution
      profile.

PMID- 30098992
TI  - PIKfyve inhibitor cytotoxicity requires AKT suppression and excessive cytoplasmic
      vacuolation.
AB  - PIKfyve phosphoinositide kinase produces PtdIns(3,5)P2 and PtdIns5P and governs a
      myriad of cellular processes including cytoskeleton rearrangements and cell
      proliferation. The latter entails rigorous investigation since the cytotoxicity
      of PIKfyve inhibition is a potential therapeutic modality for cancer. Here we
      report the effects of two PIKfyve-specific inhibitors on the attachment/spreading
      and viability of mouse embryonic fibroblasts (MEFs) and C2C12 myoblasts.
      Importantly, 18-h treatment of adherent cells with YM201636 (800 nM) and apilimod
      (20 nM) in serum-containing culture media did not affect cell viability despite
      the presence of multiple cytoplasmic vacuoles, a hallmark of PIKfyve inhibition.
      Strikingly, at the same dose and duration the inhibitors caused excessive
      cytoplasmic vacuolation, initial suppression of cell attachment/spreading and
      subsequent marked detachment/death in serum-deprived cells. The remaining
      adherent cells under serum-deprived conditions had smaller surface area, lacked
      vinculin/actin-positive focal adhesions and displayed vacuoles occupying the
      entire cytoplasm. Serum or growth factors protected against PIKfyve inhibitor
      cytotoxicity. This protection required Akt activation evidenced by the abrogated
      beneficial effect of serum upon treatment with the clinically-relevant Akt
      inhibitor MK-2206. Moreover, Akt inhibition triggered cell detachment/death even
      in serum-fed adherent MEFs treated with apilimod. Intriguingly, BafilomycinA1 (H+
      vacuolar ATPase inhibitor), which prevents the cytoplasmic vacuolation under
      PIKfyve perturbations, rescued all defects in attaching/spreading as well as in
      adherent cells under serum-starved or serum-fed conditions, respectively.
      Together, the results indicate that the cytotoxicity of PIKfyve inhibitors in
      MEFs and C2C12 myoblasts requires Akt suppression and excessive cytoplasmic
      vacuolation.

PMID- 30098993
TI  - Weighted Schatten p-norm minimization for 3D magnetic resonance images denoising.
AB  - Magnetic resonance (MR) imaging plays an important role in clinical diagnosis and
      scientific research. A clean MR image can better provide patient's information to
      doctors or researchers for further treatment. However, in real life, MR images
      are inevitably corrupted by annoying Rician noise in the process of imaging.
      Aiming at the Rician noise of 3D MR images, a framework is proposed to suppress
      noise by low-rank matrix approximation (LRMA) with weighted Schatten p-norm
      minimization regularization (WSNMD-3D). The proposed method not only considers
      the importance of different rank components, but can also approximate the true
      rank of the latent low-rank matrix. This approach first groups similar non-local
      cubic patches extracted from the noisy 3D MR image into a matrix whose columns
      are vectorized patches. The above matrix can be modeled as a low-rank matrix
      approximate model. Then weighted Schatten p-norm minimization (WSNM) is applied
      to the model, which shrinks different rank components with different treatments.
      Finally, the denoised 3D MR image is acquired by aggregating all denoised patches
      with weighted averaging. Experimental results on synthetic and real 3D MR data
      show that the proposed method obtains better results than state-of-the-art
      methods, both visually and quantitatively.

PMID- 30098994
TI  - Continuous assays for meprin alpha and beta using prolyl tripeptidyl
      aminopeptidase (PtP) from Porphyromonas gingivalis.
AB  - Common assays for endoprotease activity of meprin alpha and beta are based on
      cleavage of internally quenched substrates. Although direct and convenient, for
      meprins these assays bear disadvantages such as, e.g., significant substrate
      inhibition or potential fluorescence quenching by compounds applied in inhibitor
      analysis. Here, we present a novel continuous assay by introducing an auxiliary
      enzyme, prolyl tripeptidyl aminopeptidase (PtP) and the chromogenic substrate
      KKGYVADAP-p-nitroanilide. We provide a quick strategy for expression and one-step
      purification of the auxiliary enzyme. The enzyme kinetic data for meprin alpha
      and beta suggest hyperbolic v/S-characteristics, the kinetic parameters of
      substrate conversion by meprin beta were Km = 184 +/- 32 MUM and kcat = 20 +/- 4
      s-1. We also present conditions for the use of the fluorogenic substrate
      KKGYVADAP-AMC to assess meprin beta activity. The assays were applied for
      determination of inhibitory parameters of the natural inhibitor actinonin and two
      recently published hydroxamates. Hence, we present two novel methods, which can
      be applied to assess inhibitory mechanism and potency with the attractive current
      drug targets meprin alpha and beta. Furthermore, the assay might also provide
      implications for analysis of other endoproteases as well as their inhibitors.

PMID- 30098995
TI  - Lycopene and alpha-lipoic acid improve semen antioxidant enzymes activity and
      cashmere goat sperm function after cryopreservation.
AB  - Cashmere goats, a unique biological resource in China, have the highest cashmere
      yield and best fiber quality in the world. The goal of this study was to
      determine the effects of cryopreserving with lycopene (LP) and alpha-lipoic acid
      (ALA) on the physiological characteristics of Cashmere goat spermatozoa. The
      results showed that sperm motility, acrosome integrity, membrane integrity, and
      mitochondrial activity of goat spermatozoa were greater in extenders containing
      1.0 mg/mL LP and 10 MUg/mL ALA (P < 0.05). Furthermore, higher SOD, CAT, and GSH
      Px levels in semen occurred for extenders with 1.0 mg/mL LP and 10 MUg/mL ALA
      compared with that of other treatments and the control group (P < 0.05).
      Interestingly, this study also combined LP + ALA in the extender. The results
      showed that the sperm motility, membrane integrity, and acrosome integrity in 1.0
      mg/mL + 5 MUg/mL in the LP + ALA group were significantly elevated compared with
      that of the control group (P < 0.05). Moreover, 1.0 mg/mL + 5 MUg/mL LP + ALA
      addition increased SOD, CAT, and GSH-Px in spermatozoa more than 1.0 mg/mL LP and
      10 MUg/mL ALA (P < 0.05). In addition, the results of AI showed that the
      pregnancy rates were higher in the 1.0 mg/mL + 5 MUg/mL LP + ALA group than the
      control group (P < 0.05). In conclusion, the addition of LP + ALA to extender
      solutions protects goat spermatozoa from ROS attack by improving antioxidant
      enzymes activity, and the results suggested that freezing extenders supplemented
      with 1.0 mg/mL + 5 MUg/mL LP + ALA would be beneficial to the Cashmere goat
      breeding industry.

PMID- 30098996
TI  - Single blastocyst transfer (SET) and pregnancy outcome of day 5 and day 6 human
      blastocysts vitrified using a closed device.
AB  - This study investigates the utility of the Rapid-i closed device for
      vitrification of human blastocysts on day-5 (D5) and day-6 (D6) of development
      and the implantation and pregnancy rate following single blastocyst transfer
      (SBT) of warmed D5/D6 blastocysts. This retrospective cohort study was performed
      at Edinburgh Assisted Conception Programme, EFREC, Royal Infirmary of Edinburgh
      between January 2013 and January 2017. Good quality blastocysts were vitrified on
      D5 or D6 using Irvine Vitrification medium (Irvine Scientific-USA) and the Rapid
      I closed Vitrification SystemTM (Vitrolife, Sweden). After warming, blastocysts
      were cultured in G-TLTM medium (Vitrolife) supplemented with 20% HSA-solutionTM
      (Human Serum Albumin) for 2 h before the transfer. The survival, pregnancy and
      implantation rates were compared in relation to the day of culture at the time of
      vitrification (D5/D6) in 1090 cryopreserved cycles. The overall survival rate was
      93.4% (1018/1090) with no significant difference between the D5 and D6 groups:
      93.9% (712/758) and 92.2% (306/332) respectively. Single embryo transfers of D6
      vitrified/warmed blastocysts resulted in a lower implantation and clinical
      pregnancy rate compared to D5 embryos. The implantation rate (IPR) and clinical
      pregnancy rate (CPR) were respectively 49.6% and 43.0% for the D5 and 37.0% and
      33.0% for the D6 embryos, which was statistically significant. The multiple
      pregnancy rate was 1.08% (0.98% for D5 vs 1.3% for day 6).

PMID- 30098989
TI  - Advanced biomarkers of pediatric mild traumatic brain injury: Progress and
      perils.
AB  - There is growing public concern about neurodegenerative changes (e.g., Chronic
      Traumatic Encephalopathy) that may occur chronically following clinically
      apparent and clinically silent (i.e., sub-concussive blows) pediatric mild
      traumatic brain injury (pmTBI). However, there are currently no biomarkers that
      clinicians can use to objectively diagnose patients or predict those who may
      struggle to recover. Non-invasive neuroimaging, electrophysiological and
      neuromodulation biomarkers have promise for providing evidence of the so-called
      "invisible wounds" of pmTBI. Our systematic review, however, belies that notion,
      identifying a relative paucity of high-quality, clinically impactful, diagnostic
      or prognostic biomarker studies in the sub-acute injury phase (36 studies on
      unique samples in 28 years), with the majority focusing on adolescent pmTBI.
      Ultimately, well-powered longitudinal studies with appropriate control groups, as
      well as standardized and clearly-defined inclusion criteria (time post-injury,
      injury severity and past history) are needed to truly understand the complex
      pathophysiology that is hypothesized (i.e., still needs to be determined) to
      exist during the acute and sub-acute stages of pmTBI and may underlie post
      concussive symptoms.

PMID- 30098997
TI  - Effect of sericin supplementation on heat shock protein 70 (HSP70) expression,
      redox status and post thaw semen quality in goat.
AB  - Cryopreservation results in substantial deterioration of heat shock protein 70
      (HSP70) and ultra-structural changes in sperm organelles, resulting in a marked
      reduction in post-thaw semen quality. The present study was aimed to explicate
      the effect of sericin supplementation on expression profile of HSP70, redox
      status and post-thaw semen quality in Barbari goat. Five Barbari bucks were used
      to collect thirty semen ejaculates by using artificial vagina and each ejaculate
      was divided into three aliquots to which sericin was supplemented at 0%
      (Control), 0.25% (T1) and 0.50% (T2). Further, extended semen samples were
      equilibrated followed by their cryopreservation. Post-thaw semen characteristics,
      redox status of seminal plasma, enzyme leakage and HSP70 gene/protein expression
      in spermatozoa were assessed in all the groups. Per cent progressive motile
      spermatozoa, spermatozoa having intact plasma membrane (HOST + ve) and intact
      acrosomes in post-thaw spermatozoa were significantly (p < 0.01) higher in T1 and
      T2 as compared to control. A significant (p < 0.01) reduction in abnormal
      spermatozoa was found in T1 as compared to T2. Sericin supplementation
      significantly (p < 0.05) improved the antioxidative status (SOD, GST, CAT),
      reduced lipid peroxidation (MDA) and also prevented enzyme (ALT, LDH) leakage as
      compared to control samples. qRT-PCR results revealed that HSP70 mRNA expression
      was significantly (p < 0.01) upregulated in T1 and T2 group as compared to
      control. The positive effect of sericin on expression of HSP70 was further
      confirmed by immunoblotting followed by densitometry revealing higher expression
      in T1 and T2 compared to control. Inclusion of 0.25% w/v sericin in semen
      extender ameliorated the post-thaw semen quality by improving antioxidative
      status and minimizing the leakage of intracellular enzymes. Sericin
      supplementation had a beneficial effect on HSP70/HSP70 mRNA expression either by
      induction or by protection of HSP70/HSP70 mRNA as evident from the gene
      expression and immunoblotting studies.

PMID- 30098998
TI  - Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted
      endothelial cell junctions.
AB  - The BMP pathway regulates developmental processes including angiogenesis, yet its
      signaling outputs are complex and context-dependent. Recently, we showed that
      SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases
      vessel sprouting and branching both in vitro and in zebrafish. Genetic deletion
      of SMAD6 in mice results in poorly characterized cardiovascular defects and
      lethality. Here, we analyzed the effects of SMAD6 loss on vascular function
      during murine development. SMAD6 was expressed in a subset of blood vessels
      throughout development, primarily in arteries, while expression outside of the
      vasculature was largely confined to developing cardiac valves with no obvious
      embryonic phenotype. Mice deficient in SMAD6 died during late gestation and early
      stages of postnatal development, and this lethality was associated with vessel
      hemorrhage. Mice that survived past birth had increased branching and sprouting
      of developing postnatal retinal vessels and disorganized tight and adherens
      junctions. In vitro, knockdown of SMAD6 led to abnormal endothelial cell adherens
      junctions and increased VE-cadherin endocytosis, indicative of activated
      endothelium. Thus, SMAD6 is essential for proper blood vessel function during
      murine development, where it appears to stabilize endothelial junctions to
      prevent hemorrhage and aberrant angiogenesis.

PMID- 30098999
TI  - Folate deficiency prevents neural crest fate by disturbing the epigenetic Sox2
      repression on the dorsal neural tube.
AB  - Folate deficiency has been known to contribute to neural tube and neural crest
      defects, but why these tissues are particularly affected, and which are the
      molecular mechanisms involved in those abnormalities are important human health
      questions that remain unanswered. Here we study the function of two of the main
      folate transporters, FolR1 and Rfc1, which are robustly expressed in these
      tissues. Folate is the precursor of S-adenosylmethionine, which is the main donor
      for DNA, protein and RNA methylation. Our results show that knockdown of FolR1
      and/or Rfc1 reduced the abundance of histone H3 lysine and DNA methylation, two
      epigenetic modifications that play an important role during neural and neural
      crest development. Additionally, by knocking down folate transporter or
      pharmacologically inhibiting folate transport and metabolism, we observed ectopic
      Sox2 expression at the expense of neural crest markers in the dorsal neural tube.
      This is correlated with neural crest associated defects, with particular impact
      on orofacial formation. By using bisulfite sequencing, we show that this
      phenotype is consequence of reduced DNA methylation on the Sox2 locus at the
      dorsal neural tube, which can be rescued by the addition of folinic acid. Taken
      together, our in vivo results reveal the importance of folate as a source of the
      methyl groups necessary for the establishment of the correct epigenetic marks
      during neural and neural crest fate-restriction.

PMID- 30099000
TI  - Association between physical exercise and mental health in 1.2 million
      individuals in the USA between 2011 and 2015: a cross-sectional study.
AB  - BACKGROUND: Exercise is known to be associated with reduced risk of all-cause
      mortality, cardiovascular disease, stroke, and diabetes, but its association with
      mental health remains unclear. We aimed to examine the association between
      exercise and mental health burden in a large sample, and to better understand the
      influence of exercise type, frequency, duration, and intensity. METHODS: In this
      cross-sectional study, we analysed data from 1 237 194 people aged 18 years or
      older in the USA from the 2011, 2013, and 2015 Centers for Disease Control and
      Prevention Behavioral Risk Factors Surveillance System survey. We compared the
      number of days of bad self-reported mental health between individuals who
      exercised and those who did not, using an exact non-parametric matching procedure
      to balance the two groups in terms of age, race, gender, marital status, income,
      education level, body-mass index category, self-reported physical health, and
      previous diagnosis of depression. We examined the effects of exercise type,
      duration, frequency, and intensity using regression methods adjusted for
      potential confounders, and did multiple sensitivity analyses. FINDINGS:
      Individuals who exercised had 1.49 (43.2%) fewer days of poor mental health in
      the past month than individuals who did not exercise but were otherwise matched
      for several physical and sociodemographic characteristics (W=7.42 * 1010, p<2.2 *
      10-16). All exercise types were associated with a lower mental health burden
      (minimum reduction of 11.8% and maximum reduction of 22.3%) than not exercising
      (p<2.2 * 10-16 for all exercise types). The largest associations were seen for
      popular team sports (22.3% lower), cycling (21.6% lower), and aerobic and gym
      activities (20.1% lower), as well as durations of 45 min and frequencies of three
      to five times per week. INTERPRETATION: In a large US sample, physical exercise
      was significantly and meaningfully associated with self-reported mental health
      burden in the past month. More exercise was not always better. Differences as a
      function of exercise were large relative to other demographic variables such as
      education and income. Specific types, durations, and frequencies of exercise
      might be more effective clinical targets than others for reducing mental health
      burden, and merit interventional study. FUNDING: Cloud computing resources were
      provided by Microsoft.

PMID- 30099001
TI  - Exercise and mental health: a complex and challenging relationship.

PMID- 30099003
TI  - EPA + DHA in Prevention of Early Preterm Birth - Do We Know How to Apply it?

PMID- 30099004
TI  - Not one hormone or another: Aggression differentially affects progesterone and
      testosterone in a South American ovenbird.
AB  - Behaviors such as territorial interactions among individuals can modulate
      vertebrate physiology and vice versa. Testosterone has been pointed out as a key
      hormone that can be rapidly affected by aggressive interactions. However,
      experimental evidence for such a link is mixed. In addition, behaviors can elicit
      changes in multiple hormones, which in turn have the potential to synergistically
      feedback to behavior. For example testosterone and progesterone can act
      interdependently in modulating male behavior. However, if aggression can affect
      progesterone levels in males remain unknown and - to the best of our knowledge -
      no one has yet tackled if and how aggressive behavior simultaneously affects
      testosterone and progesterone in free-living animals. We addressed these
      questions by performing simulated territorial intrusion experiments measuring
      both hormones and their ratio in male rufous horneros (Aves, Furnarius rufus)
      during the mating and parental care periods. Aggression affected testosterone and
      progesterone differentially depending on the period of testing: challenged birds
      had higher levels of progesterone during the mating period and lower levels of
      testosterone during parental care compared to controls. Challenged individuals
      had similar progesterone to testosterone ratios during both periods and these
      ratios were higher than those of control birds. In summary, territorial
      aggression triggered hormonal pathways differentially depending on the stage of
      the breeding cycle, but equally altered their ratio independent of it. Our
      results indicate that multiple related hormones could be playing a role rather
      than each hormone alone in response to social interactions.

PMID- 30099005
TI  - Sensitive and rapid detection of Salmonella enterica serovar Indiana by cross
      priming amplification.
AB  - Salmonella enterica serovar Indiana (S. Indiana) was the most frequently reported
      foodborne pathogen, which has a broad host range including poultry, swine, and
      humans. Traditional methods used for the detection of S. Indiana from
      contaminated food products are time-consuming and labor-intensive. Therefore,
      rapid detection methods with high sensitivity and specificity are vitally
      important to prevent the spread of S. Indiana. In this study, we developed a
      nearly instrument-free, simple molecular method which incorporates cross-priming
      amplification (CPA) combined with a nucleic acid detection strip (NADS) for
      sensitive detection of S. Indiana. A set of CPA primers was designed based on S.
      Indiana specific nucleotide sequences and the specificity of CPA-NADS was tested
      against 42 bacterial strains. The results showed that this method was highly
      specific for detection of S. Indiana. The sensitivity of CPA-NADS was evaluated
      and compared with that of the serovar-specific PCR method and the real-time PCR
      method. The limit of detection of the CPA method was 8.997 fg/MUL for genomic DNA
      and 6.2 * 101 CFU/mL for bacteria in pure culture. An application of the CPA
      assay was conducted with 90 inoculated specimens by S. Indiana. The accuracy of
      CPA-NADS was consistent with the results of the traditional culture-based methods
      in inoculated specimens. This method showed a higher sensitivity than the serovar
      specific PCR method did and was more convenient to perform. In conclusion, we
      demonstrated that the CPA-NADS system offers high specificity, sensitivity,
      rapidity, and a simple detection tool for screening S. Indiana.

PMID- 30099007
TI  - Adenosine activates Galphas proteins and inhibits C3a-induced activation of human
      mast cells.
AB  - Anaphylatoxin C3a and adenosine receptors (AR) are implicated in the inflammatory
      process associated with allergic rhinitis and asthma by modifying mast cell (MC)
      responses. Possible interactions between these G-protein coupled receptor (GPCR)
      pathways in MCs have not yet been demonstrated. LAD2 human MC were stimulated
      with C3a in the presence or absence of AR agonists and antagonists and their
      adhesion, chemotaxis and mediator release were measured. The pan-specific AR
      agonist, 5'-N-Ethylcarboxamidoadenosine (NECA) inhibited C3a-induced LAD2 cell
      migration, adhesion, degranulation, production of CCL2, and ERK1/2
      phosphorylation. The selective A2A receptor agonist CGS 21680 inhibited C3a
      mediated degranulation, while the A2B and A3 receptor agonists BAY 60-6583 and IB
      MECA, respectively, had no effect. Moreover, an A2A receptor antagonist SCH 58261
      blocked the inhibitory effect of NECA on C3a-induced degranulation, suggesting
      that inhibition of degranulation was mediated through the A2A receptor. NECA
      increased intracellular cAMP in C3a-activated mast cells, suggesting that Galphas
      protein signals are required for adenosine-induced inhibition of C3a-mediated
      human mast cell activation. The adenylyl cyclase inhibitor SQ 22536 attenuated
      the inhibitory effect of NECA on C3a-activated degranulation, and the A2A agonist
      CSG 21680 potentiated the inhibition of mast cell activation mediated by the A2A
      receptor. Our results suggest that adenosine inhibits C3a-mediated activation of
      human mast cells, possibly through a Galphas protein-dependent pathway.

PMID- 30099008
TI  - Modulation of nitric oxide-stimulated soluble guanylyl cyclase activity by
      cytoskeleton-associated proteins in vascular smooth muscle.
AB  - Soluble guanylyl cyclase (sGC, EC 4.6.1.2) is a key enzyme in the regulation of
      vascular tone. In view of the therapeutic interest of the NO/cGMP pathway, drugs
      were developed that either increase the NO sensitivity of the enzyme or activate
      heme-free apo-sGC. However, modulation of sGC activity by endogenous agents is
      poorly understood. In the present study we show that the maximal activity of NO
      stimulated purified sGC is significantly increased by cytosolic preparations of
      porcine coronary arteries. Purification of the active principle by several
      chromatographic steps resulted in a protein mixture consisting of 100, 70, and 40
      kDa bands on SDS polyacrylamide gel electrophoresis. The respective proteins were
      identified by LC-MS/MS as gelsolin, annexin A6, and actin, respectively. Further
      purification resulted in loss of activity, indicating an interaction of sGC with
      a protein complex rather than a single protein. The partially purified
      preparation had no effect on basal sGC activity or enzyme activation by the heme
      mimetic BAY 60-2770, suggesting a specific effect on the conformation of the NO
      bound heterodimeric holoenzyme. Since the three proteins identified are all
      related to contractile elements of smooth muscle, our data suggest that
      regulation of vascular tone involves a modulatory interaction of sGC with the
      cytoskeleton.

PMID- 30099002
TI  - Miniature pig magnetic resonance spectroscopy model of normal adolescent brain
      development.
AB  - BACKGROUND: We are developing the miniature pig (Sus scrofa domestica), an in
      vivo translational, gyrencephalic model for brain development, as an alternative
      to laboratory rodents/non-human primates. We analyzed longitudinal changes in
      adolescent pigs using proton magnetic resonance spectroscopy (1H-MRS) and
      examined the relationship with white matter (WM) integrity derived from diffusion
      weighted imaging (DWI). NEW METHOD: Twelve female SinclairTM pigs underwent three
      imaging/spectroscopy sessions every 23.95 +/- 3.73 days beginning at three months
      of age using a clinical 3 T scanner. 1H-MRS data were collected using 1.2 * 1.0 *
      3.0 cm voxels placed in left and right hemisphere WM using a Point Resolved
      Spectroscopy sequence (TR = 2000 ms, TE = 30 ms). Concentrations of N
      acetylaspartate, myo-inositol (MI), glutamate + glutamine, choline, creatine, and
      macromolecules (MM) 09 and 14 were averaged from both hemispheres. DWI data were
      collected using 15 shells of b-values (b = 0-3500 s/mm2) with 32 directions/shell
      and fit using the WM Tract Integrity model to calculate fractional anisotropy
      (FA), kurtosis anisotropy (KA) and permeability-diffusivity index. RESULTS: MI
      and MM09 significantly declined with age. Increased FA and KA significantly
      correlated with decline in MI and MM09. Correlations lost significance once
      corrected for age. COMPARISON WITH EXISTING METHODS: MRI scanners/protocols can
      be used to collect 1H-MRS and DWI data in pigs. Pigs have a larger, more complex,
      gyrencephalic brain than laboratory rodents but are less complex than non-human
      primates, thus satisfying the "replacement" principle of animal research.
      CONCLUSIONS: Longitudinal effects in MRS measurements were similar to those
      reported in adolescent humans. MRS changes correlated with diffusion measurements
      indicating ongoing WM myelination/maturation.

PMID- 30099010
TI  - Immune and biochemical responses in hemolymph and gills of the Patagonian
      freshwater mussel Diplodon chilensis, against two microbiological challenges:
      Saccharomyces cerevisiae and Escherichia coli.
AB  - Immune cell characterization, immunological response and the associated gill
      oxidative balance were studied in the Patagonian freshwater mussel, Diplodon
      chilensis, using two microbiological immunostimulant models: Saccharomyces
      cerevisiae and Escherichia coli. Mussels were collected out of the breeding
      season in Paimun Lake and acclimated in the laboratory. Two exposure experiments
      were performed during two consecutive weeks: (1) mussels challenged with 500
      yeast cells mL-1; and (2) mussels challenged with 1000 bacteria cells mL-1.
      Microorganisms were added in the water every two days, alternating with 6000
      lyophilized cells of the green algae Scenedesmus vacuolatus mL-1. A control
      group, fed with S. vacuolatus, was set for each treatment. Morphological cell
      characterization was carried out in adherent hemocytes of D. chilensis hemolymph
      under control conditions. The most important cell type observed were the
      hyalinocytes (representing ca. 98% of the circulating cells), agranular cells
      with non-central polymorphic nucleus surrounded by cytoplasm; granulocytes (cells
      with cytoplasmic granules and non-central rounded nucleus) represented ca. 2%.
      Another two cell types were occasionally detected, binucleated hyalinocytes and
      hemoblast-like cells but were not considered for the analyses. Both adherent
      hyalinocytes and granulocytes exhibit phagocytic activity towards Congo red
      stained yeast, which was two-fold higher in granulocytes than in hyalinocytes,
      regardless of the applied challenge. Total hemocyte counts were diminished in
      mussels challenged with S. cerevisiae or E. coli. Hydrolytic and defense cellular
      enzyme activities were analyzed only for hyalinocytes. Both, S. cerevisiae and E.
      coli increased acid phosphatase activity. E. coli challenge diminished hemocyte
      lysosomal membrane stability and increased humoral phenoloxidase activity, while
      S. cerevisiae challenge did not affect any of these variables. Mussels challenged
      with E. coli showed increased gill antioxidant response without oxidative damage,
      while those challenged with S. cerevisiae showed no change in these variables.

PMID- 30099009
TI  - Promising new therapeutic targets for regulation of inflammation and immunity:
      RING-type E3 ubiquitin ligases.
AB  - Ubiquitin-proteasome system (UPS) is a primary signaling pathway for regulation
      of protein turnover and removal of misfolded proteins in eukaryotic cells.
      Enzymes of the UPS pathway - E1 activating, E2 conjugating, E3 ligating - act
      together to covalently tag substrate proteins with a chain of ubiquitins, small
      regulatory proteins. The poly-ubiquitin chain then serves as a recognition motif
      for 26S proteasome to recognize and degrade the substrate. In recent years UPS
      has emerged as attractive enzymatic cascade for development of novel therapeutics
      against various human diseases. Building on the previous success of targeting
      this pathway in cancer - the broader scientific community is currently looking
      for ways to elucidate functions of E3 ligases, substrate-specific members of the
      UPS. RING-type E3 ubiquitin ligases, the largest class of E3s, represent
      prospective targets for small molecule modulation and their importance is
      reinforced by ever growing evidence of playing role in non-cancer diseases,
      primarily associated with inflammatory and immune disorders. In this review, we
      aim to briefly cover the current knowledge of biological functions of RING-type
      E3 ligases in inflammation and immunity.

PMID- 30099006
TI  - Selective up-regulation of cannabinoid CB1 receptor coupling to Go-proteins in
      suicide victims with mood disorders.
AB  - Brain endocannabinoid system is proposed to play a role in the pathogenesis of
      affective disorders. In the present study, we analyzed the functionality of the
      cannabinoid receptor type 1 (CB1 receptor) at different transduction levels in
      prefrontal cortex (PFC) of depressed suicide victims. We examined stimulation of
      [35S]GTPgammaS binding, activation of Galpha protein subunits and inhibition of
      adenylyl cyclase by the cannabinoid agonist WIN55,212-2, as well as [3H]CP55,940
      binding, in PFC homogenates from suicide victims with major depression (MD) and
      matched control subjects. CB1 receptor-stimulated [35S]GTPgammaS binding was
      significantly greater in the PFC of MD compared with matched controls (23%, p <
      0.05). This increase was most evident in the PFC from MD subgroup with negative
      blood test for antidepressants (AD) at the time of death (AD-free) (38%, p <
      0.05), being absent when comparing the AD-treated MD cases with their controls.
      The density of CB1 receptors and their coupling to adenylyl cyclase were similar
      between MD and control cases, regardless of the existence of AD intake. Analysis
      of [35S]GTPgammaS-labelled Galpha subunits allowed for the detection of
      upregulated CB1 receptor coupling to Galphao, but not to Galphai1, Galphai2,
      Galphai3, Galphaz subunits, in the PFC from AD-free MD suicides. These results
      suggest that increased CB1 receptor functionality at the Galphai/o protein level
      in the PFC of MD subjects is due to enhanced coupling to Galphao proteins and
      might be modulated by AD intake. These data provide new insights into the role of
      endocannabinoid neurotransmission in the pathobiology of MD and suggest its
      regulation by ADs.

PMID- 30099011
TI  - Genomic abnormalities affecting mussels (Mytilus edulis-galloprovincialis) in
      France are related to ongoing neoplastic processes, evidenced by dual flow
      cytometry and cell monolayer analyses.
AB  - In the context of the abnormal mass mortality of mussels in France since 2014,
      Flow CytoMetry (FCM) was used in 2015 and 2016 to study the DNA content and cell
      cycle characteristics of hemic circulating cells collected from 2000 mussels. The
      mussels were sampled from 12 wild and cultivated blue mussels stocks distributed
      along the French Atlantic coast from the south Brittany to Pertuis Charentais
      areas. During these surveys, various genetic abnormalities were frequently
      detected, and ploidy characteristics revealed contrasting profiles that
      corresponded to respective contrasting sanitary status, i.e. healthy mussels with
      high cytogenetic quality (HCQ) versus diseased mussels with low cytogenetic
      quality (LCQ). In the present work, FCM and hemocytology cell monolayer
      techniques were combined in order to determine the putative causes of the
      observed genetic abnormalities that were significantly associated with mortality
      levels. FCM and cell monolayer approaches permitted the definition of new
      threshold values delimiting HCQ mussels from LCQ ones. FCM histograms of mussels
      from the HCQ group showed one single or a largely dominant population of diploid
      (2n) nuclei and a large majority of normal hemocytes. Hemolymph cell-monolayer
      analyses showed predominantly acidophil granulocytes characterized by nuclei of
      normal size and a large cytoplasm with numerous granulations. In contrast, FCM
      histograms for the LCQ group showed, in addition to the normal diploid (2n)
      nuclei, populations of nuclei that displayed aneuploidy patterns in a broad
      ploidy range, including diploid-triploid (2-3n), tetraploid-pentaploid (4-5n) and
      heptaploid-octaploid levels (7-8n). The corresponding hemolymph cell-monolayer
      showed cellular features characteristic of disseminated neoplasia disease with
      frequent abnormal anaplastic cells that exhibited noticeable numbers of mitotic
      figures with both normal and aberrant chromosomes segregation patterns. These
      neoplastic cells were a rounded shape with a reduced, granulation-free cytoplasm
      and large (11-12 um) to very large (up to 21 um) round or ovoid nuclei that
      correspond to the 4-5n and 7-8n nuclei previously detected by FCM analyses. These
      characteristics suggest that the genetic abnormalities detected by means of FCM
      were related to an ongoing neoplastic process that is affecting blue mussels in
      France, at least since the onset in 2014 of the mortality that heavily impacted
      French blue mussels stocks.

PMID- 30099013
TI  - Steroid hormones induce in vitro human first trimester trophoblast tubulogenesis
      by the lysophosphatidic acid pathway.
AB  - Successful implantation and placentation requires that extravillous
      cytotrophoblast acquires an endovascular phenotype and remodels uterine spiral
      arteries. Progesterone (P4) and estradiol (E2) control many of the placental
      functions, but their role in vascular remodeling remains controversial. Here, we
      investigated whether P4 and E2 regulate the acquisition of the human first
      trimester trophoblast endovascular phenotype, and the participation of the
      lysophosphatidic acid pathway. For this purpose, human first trimester HTR
      8/SVneo cells were seeded on Geltrex and assayed for capillary-like tube
      formation. P4 and E2 increased HTR-8/SVneo tube formation in a concentration
      dependent manner and this effect is mediated by the LPA3 receptor. Moreover, sex
      steroids increased the mRNA levels of the main enzyme that produce
      lysophosphatidic acid (lysophospholipase-D) but did not regulate LPA3 mRNA
      levels. Overall, we demonstrate that steroid hormones regulate HTR-8/SVneo
      trophoblast capillary-like structures formation and we propose that this process
      could be modulated directly or indirectly by mechanisms associated to the
      LPA/LPA3 pathway.

PMID- 30099012
TI  - Larvicidal potential of Skermanella sp. against rice leaf folder (Cnaphalocrosis
      medinalis Guenee) and pink stem borer (Sesamia inferens Walker).
AB  - Insect pests in the rice agroecosystem, particularly the leaf folder,
      Cnaphalocrosis medinalis (Guenee) and stem borer, Sesamia inferens (Walker),
      cause significant yield losses. These pests are generally managed by farmers by
      application of insecticides and a few biocontrol agents. As a component of
      integrated pest management, biocontrol agents play a dynamic role in pest
      control. Although diverse microbial communities are available in the rice
      ecosystem, bacterial genera such as Bacillus and Pseudomonas spp. are broadly
      used as biocontrol agents. Therefore, an attempt was made to identify other
      effective entomopathogenic bacteria to manage the above mentioned pests. In this
      study, the two entomopathogenic bacteria isolated from diseased pink stem borer
      (S. inferens Walker) larvae collected from rice fields were identified as
      Skermanella sp. (KX611462) and Serratia sp. (KX761232). The larvicidal activity
      of these two bacteria was evaluated against third instar larvae of C. medinalis
      and S. inferens in in vitro assays and on potted rice plants (Oryza sativa var.
      TN1). The results of this study demonstrated 50% (LC50) larval mortality of C.
      medinalis at 2.95 * 103 and 5.88 * 103 colony forming units (CFU) ml-1 for
      Skermanella sp. and Serratia sp., respectively, under in vitro conditions, 2.57 *
      104 and 3.38 * 104 CFU ml-1, respectively, in whole plant assays. Similarly, the
      LC50 value for Skermanella sp. was 3.80 * 104 CFU ml-1 and Serratia sp. was 2.29
      * 105 CFU ml-1 for S. inferens larvae. Our study reports the larvicidal activity
      of Skermanella sp. against C. medinalis and S. inferens.

PMID- 30099014
TI  - Bead-extraction and heat-dissociation (BEHD): A novel way to overcome drug and
      matrix interference in immunogenicity testing.
AB  - Biological therapeutics are foreign antigens and can potentially induce immune
      response resulting in the formation of anti-drug antibodies (ADA), which in turn
      may lead to a wide range of side effects. Neutralizing Ab (NAb) is a subset of
      ADA that can bind to the pharmacological activity regions of therapeutic to
      inhibit or complete neutralize its clinical efficacy. A cell-based functional NAb
      assay is preferred to characterize its neutralization activity. However, cell
      based NAb assays are often vulnerable to drug interference, as well as
      interference from numerous serum factors, including but not limited to growth
      factors and disease-related cytokines. Bead Extraction with Acid Dissociation
      (BEAD) has been successfully applied to remove circulating drug and/or other
      interfering factors from human serum samples, thereby enriching for ADA/NAb.
      However, the harsh acid used in the extraction procedure can cause irreversible
      denaturing of NAb and lead to underestimated NAb measurement. Herein we describe
      a new approach when acid-dissociation is not optimal for a PEGylated domain
      antibody (Ab). We further demonstrate that heating at 62  degrees C can not only
      dissociate drug/ADA/NAb immune complex but also selectively and irreversibly
      denature domain Ab drug due to much lower thermal stability of the domain Ab,
      when compared to that of full antibodies. The irreversible denaturing of the drug
      favors the formation of an immune complex between ADA/NAb and the added
      biotinylated drug thus increasing the recovery of ADA/NAb from samples. We call
      this new procedure Bead Extraction with Heat Dissociation (BEHD), which can
      potentially be applied to other NAb assays that have poor compatibility with acid
      dissociation.

PMID- 30099015
TI  - Enhanced quantification of serum immunoglobulin G from a non-model wildlife
      species, the Steller sea lion (Eumetopias jubatus), using a protein A ELISA.
AB  - Immunoglobulins (Ig) are proteins that preserve immune homeostasis and are
      quantified to infer changes to the acquired humoral immune response in mammals.
      Measuring Ig in non-model wildlife for immune surveillance often requires
      ingenuity, and rigorous standardization of methodologies to provide reliable
      results especially when lacking species-specific reagents. We modified and
      optimized existing ELISA methodology utilizing the binding properties of
      Staphylococcus-derived Protein A (PrtA) to immunoglobulin G (IgG). We enhanced
      the assay for quantifying IgG in Steller sea lion (SSL) serum using critical
      quality control measures including dilution linearity, spike and percent
      recoveries, and internal controls. Of the modifications made, heat treatment of
      SSL serum enhanced accuracy and precision of IgG measurements by improving
      linearity and percent recovery in parallel dilutions and serum spikes. Purified
      canine IgG standard was not affected by heat inactivation. These results support
      that confounding serum proteins interfere with binding of PrtA with IgG
      demonstrating the need for heat treatment of serum to optimize IgG quantification
      using the PrtA-ELISA. Further, essential validation measures ensure proper assay
      performance. Consequently, the improved PrtA-ELISA provides species-independent
      IgG detection with validation criteria to enhance accuracy and precision for
      addressing future immunological questions in non-model wildlife in clinical,
      ecological, and conservation contexts.

PMID- 30099016
TI  - Patency of the supraclinoid internal carotid artery branches after flow diversion
      treatment. A meta-analysis.
AB  - BACKGROUND AND PURPOSE: Placement of flow-diverters across the ostia of major ICA
      branches carries a risk of arterial occlusion. We determined the rate of
      occlusion of the supraclinoid ICA branches and the related symptoms, following
      coverage with flow-diverters. MATERIALS AND METHODS: A systematic search was
      performed in PubMed, MEDLINE, and EMBASE. We selected studies reporting
      treatments with flow-diverters in which the device was placed across the ostium
      of the OphtA, PcomA, or AchorA. Random-effects meta-analysis was used to pool the
      following outcomes: rate of arterial occlusion, diminished flow, incidence of
      related symptoms, factors associated with arterial occlusion. RESULT: Twenty-one
      studies evaluating 1152 supraclinoid ICA branches were included in the meta
      analysis. The incidence of OphtA occlusion and associated symptoms was 5.9% (95
      CI% = 3.1-8.6%) (incidence rate = 6% per patient-year), and 0.8% (95% CI = 0.1
      1.4%) (incidence rate = 0.8% per patient-year), respectively. Although
      asymptomatic in all cases, PcomA showed a higher occlusion rate (20.7%, 95% CI =
      8.9-32.4%) (incidence rate = 19.5% per patient-year). AchorA was occluded in 1%
      (95% CI = 0.3-2.4%) of cases, with approximately 1% (95% CI = 0.4-2.3%) of
      transient neurological symptoms (incidence rate = 0.96% per patient-year). There
      was a trend toward higher odds of arterial patency among arteries arising from
      the aneurysm (OR = 2.94, P = 0.06). Demographic factors and multiple stents were
      not associated with higher risk of arterial impairment. Adequate collateral
      circulation was reported in 94.5% of patients with arterial occlusion.
      CONCLUSIONS: During aneurysm treatment, the ostium of the supraclinoid ICA
      branches can be covered with flow-diverter devices with low rates of neurological
      symptoms related to arterial occlusion.

PMID- 30099017
TI  - Dual receptor recognizing liposomes containing paclitaxel and hydroxychloroquine
      for primary and metastatic melanoma treatment via autophagy-dependent and
      independent pathways.
AB  - Autophagy acts as a cytoprotective mechanism for malignant tumors, thus
      maintaining the survival and promoting proliferation and metastasis of malignant
      tumors. Recent studies have showed that autophagy inhibitors can enhance the
      chemotherapeutic efficacy of anti-tumor growth. However, the antimetastasis
      effects and the possible mechanisms of chemotherapeutics combined with autophagy
      inhibitors have not been thoroughly explored. Here, we prepared R8-dGR peptide
      modified paclitaxel (PTX) and hydroxychloroquine (HCQ) co-loaded liposomes
      (PTX/HCQ-R8-dGR-Lip) for enhanced delivery by recognizing integrin alphavbeta3
      receptors and neuropilin-1 receptors on B16F10 melanoma cells. Our results showed
      that R8-dGR modified liposomes (R8-dGR-Lip) enhanced tumor-targeting delivery in
      vitro and in vivo. Besides, PTX/HCQ-R8-dGR-Lip exhibited the optimum inhibitory
      effects on migration, invasion and anoikis resistance of B16F10 cells in vitro,
      and showed enhanced efficiency on inhibiting primary tumor growth and reducing
      lung metastasis in vivo. Meanwhile, the antimetastasis mechanism studies
      confirmed that the combination of the chemotherapeutic PTX and the autophagy
      inhibitor HCQ further suppressed the degradation of paxillin, the expression of
      MMP9 and MMP2. Moreover, HCQ disturbed the CXCR4/CXCL12 axis which could induce
      invasion and metastasis of malignant melanoma in an autophagy-independent way.

PMID- 30099018
TI  - A facile route to heterotelechelic polymer prodrug nanoparticles for imaging,
      drug delivery and combination therapy.

PMID- 30099019
TI  - Macrophage-targeted drugamers with enzyme-cleavable linkers deliver high
      intracellular drug dosing and sustained drug pharmacokinetics against alveolar
      pulmonary infections.
AB  - Intracellular bacterial infections localized to the lung alveolar macrophage (AM)
      remain one of the most challenging settings for antimicrobial therapy. Current
      systemic antibiotic treatment fails to deliver sustained doses to intracellular
      bacterial reservoirs, which necessitates prolonged treatment regimens. Herein, we
      demonstrate a new intracellular enzyme-cleavable polymeric prodrug with tailored
      ciprofloxacin release profiles in the lungs and AM. The targeted polymeric
      prodrug, termed "drugamers", incorporates (1) hydrophilic mannose residues to
      solubilize the antibiotic cargo and to target and enhance AM uptake and
      intracellular delivery, and (2) enzyme-cleavable linkage chemistry to provide
      high and sustained intracellular AM drug dosing. Prodrug monomers, derived from
      the antibiotic ciprofloxacin, were synthesized with either an intracellular
      protease cleavable dipeptide linker or a hydrolytic phenyl ester linker. RAFT
      polymerization was used to copolymerize the prodrug monomers and mannose monomer
      to synthesize well-defined drugamers without requiring a post-polymerization
      conjugation step. In addition to favorable in vivo safety profiles following
      intratracheal administration, a single dose of the drugamers sustained
      ciprofloxacin dosing in lungs and AMs above the minimum inhibitory concentration
      (MIC) over at least a 48 h period. The enzyme-cleavable therapeutic achieved a
      >10-fold increase in sustained ciprofloxacin in AM, and maintained a
      significantly higher whole lung PK as well. Ciprofloxacin dosed in identical
      fashion displayed rapid clearance with a half-life of approximately 30 min.
      Notably, inhalation of the mannose-targeted ciprofloxacin drugamers achieved full
      survival (100%) in a highly lethal mouse model of pneumonic tularemia, contrasted
      with 0% survival using free ciprofloxacin. These findings demonstrate the
      versatility of the drugamer platform for engineering the intracellular
      pharmacokinetic profiles and its strong therapeutic activity in treating
      pulmonary intracellular infections.

PMID- 30099020
TI  - Mechanism of MEN1 gene in radiation-induced pulmonary fibrosis in mice.
AB  - OBJECTIVE: To investigate the regulatory mechanism of MEN1 gene in radiation
      induced lung fibrosis in mice and provide a new theoretical basis for the
      clinical treatment of radiation pulmonary fibrosis. METHODS: First, 80 C57BL/6
      mice aged 8 weeks and weighing 18-22 g were selected, half of them were male and
      the other half were female. The mice were divided into control group and
      irradiation group (40 mice in each group) according to the method of the random
      number table. A radiation-induced lung fibrosis mouse model was established in
      which a single X-ray irradiation of 20 Gy was applied to the right lung in the
      irradiation group; H&E and Masson staining were used to verify whether the model
      was successful at 4, 8, 16 and 24 weeks after irradiation. The expression of
      MEN1, smooth muscle actin (alpha-SMA), Collagen-1 and transforming growth factor
      (TGF-beta) in lung tissue were detected by Western blot and qPCR. Secondly, in
      the mouse embryonic fibroblast cell line (MEF) and mouse lung epithelial cell
      line (MLE-12), we constructed cell models of MEN1 knockout and interference
      separately with the irradiation of 10 Gy X-rays. The expression of alpha-SMA,
      Collagen-1, and TGF-beta/Smads signaling pathway molecules was detected by qPCR.
      Finally, using the immunoprecipitation (IP) method, we can detect the interaction
      between Smad2 and the protein menin encoded by the MEN1 gene. RESULTS: The
      results of the radiation pulmonary fibrosis model in mice showed that compared
      with the control group, the alveolar septum widens, the alveolar integrity
      decreases, the lung tissue slightly thickens, and a small amount of collagen
      deposits appear after 4-8 weeks in the model group. At twenty-fourth weeks, a
      large number of cells in the interstitial space of the lung tissue and a
      localized focal fibrosis area were observed. Further study found that radiation
      induced fibrogenic inflammatory cytokines TGF-beta up-regulation, down-regulation
      of MEN1 gene expression, and then enhanced the expression of alpha-SMA and
      promotes the transformation of fibroblasts to myofibroblasts; At the same time,
      the expression of Collagen-1 was enhanced, which suggested that the extracellular
      matrix was overconcentrated and eventually promoted the formation of pulmonary
      fibrosis. In vitro, we found that knockout and interference of MEN1 gene can
      significantly enhance radiation-induced fibrosis, and up-regulate the expression
      of downstream molecules Smad2 and Smad3 of TGF-beta signaling pathway, and down
      regulate the expression of Smad7. Furthermore, it played an important role in
      regulating the process of radionuclide fibrosis. CONCLUSION: MEN1 plays a key
      role in the formation of pulmonary fibrosis by regulating the secretion of TGF
      beta and the activation of TGF-beta/Smads signaling pathway.

PMID- 30099021
TI  - Novel copy number variation of the KLF3 gene is associated with growth traits in
      beef cattle.
AB  - Copy number variation (CNV) related to complex traits, such as disease and
      quantitative phenotype, is considered an important and wealthy source of genetic
      and phenotypic diversity. It suggests that the copy number variation of function
      gene maybe leads to the phenotypic changes. Kupple like factor 3 (KLF3) gene is a
      vital transcription factor associated with the growth and development of muscle
      and adipose tissue. It has been mapped in a CNV region by animal genome re
      sequencing. In this study, we detected the distribution diversity of KLF3 gene
      copy numbers in six Chinese cattle breeds (QC, NY, XN, PN, QDM and JX) and
      associated the phenotypic traits with it. Then, we analyzed the KLF3 gene
      transcription expression level in different tissues of Jiaxian (JX) cattle.
      Furthermore, we detected mRNA expression level of muscle and fat tissues of
      Jiaxian cattle (JX), Angus * Jiaxian (AJ). The results showed that the copy
      number in CNV loss was more frequent in QC than others. And we revealed a
      positive effect of KLF3 CNV on growth traits, such as body mass and heart girth
      (P < 0.05). In a word, we ascertained the significance between CNVs of KLF3 gene
      and growth traits in different cattle breeds, and our data indicates that the
      CNVs of KLF3 gene may as a marker for the future molecular breeding of Chinese
      beef cattle.

PMID- 30099022
TI  - Network analysis reveals the co-expression of sugar and aroma genes in the
      Chinese white pear (Pyrus bretschneideri).
AB  - The quality of pear and other fruit affects their economic value by determining
      their attractiveness to the consumer. For this reason the two most important
      quality traits, namely the sugar content and the aroma, have been the focus of
      much research. This research has been conducted both on the biochemical
      characteristics of sugar and aroma of fruits and on the activity of enzymes
      related to their metabolism. In this study, by analyzing the transcriptome of
      pear fruit, we built the first co-expression network of the genes related to
      sugar metabolism and those related to aroma, to reveal their connections. Genes
      that encode beta-glucosidases and sorbitol dehydrogenases are shown to be the hub
      genes within this network. This study has demonstrated the power of such network
      analysis for the first time in a non-model organism. Our research can lead to new
      discoveries that go beyond the previous focus on individual genes.

PMID- 30099023
TI  - Generation of osteoclasts from type 1 Gaucher patients and correlation with
      clinical and genetic features of disease.
AB  - Gaucher disease (GD) is a rare autosomal recessive disorder caused by deficient
      activity of beta-glucocerebrosidase resulting in the accumulation of
      glucosylceramide. Bone disease is a common feature with radiological evidence in
      up to 93% of patients. Severity of bone involvement ranges from osteoporosis to
      pathological fractures. The progressive course of type 1 GD is largely mitigated
      by treatment with enzyme replacement therapy (ERT) or substrate reduction. A
      number of studies have shown some patients suffer bone events while receiving
      ERT. Studies of biochemical markers of bone turnover have generated varied
      results and as a consequence are not generally used to assess bone disease in GD.
      In vitro osteoclast generation from peripheral blood samples of 74 Gaucher
      patients followed over a period of up to 10 years was correlated with bone
      events, reports of bone pain, anaemia, spleen status, bone mineral density,
      chitotriosidase activity, treatment with Gaucher specific therapies,
      bisphosphonates, mutation status and severity. Osteoclast generation, enumerated
      when cultured on glass, was significantly higher when differentiated from the
      peripheral blood of Gaucher patients which reported bone pain (116.4 +/- 18.0 vs
      69.0 +/- 8.6, p < 0.01), had anaemia (153.7 +/- 34.9 vs 78.5 +/- 8.8, p < 0.01),
      had a splenectomy (137.6 +/- 41.1 vs 60.8 +/- 13.0, p < 0.05), versus those who
      did not. Osteoclast generation was also indicative of in vivo Gaucher specific
      therapy response as those naive to therapy generated significantly more
      osteoclasts than those on therapy (111.2 +/- 35.8 vs 45.1 +/- 10.3, p < 0.05), as
      did patients receiving therapy but still suffering bone events (125.1 +/- 31.37
      vs 45.1 +/- 10.33, p < 0.05). These findings demonstrate that the in vitro
      osteoclast assay may be a useful method for following bone disease progression in
      Gaucher patients.

PMID- 30099024
TI  - Modulation of porcine microRNAs associated with apoptosis and NF-kappaB signaling
      pathways in response to Salmonella enterica serovar Typhimurium.
AB  - MicroRNAs (miRNAs) are small, non-coding RNAs that regulate eukaryotic gene
      expression at the post-transcriptional level. In addition to their involvement in
      a variety of biological processes, miRNAs are implicated in the eukaryotic
      response to bacterial pathogens. The objective of this study was to identify
      miRNAs involved in the regulation of the porcine response to the human foodborne
      pathogen, Salmonella enterica serovar Typhimurium (S. Typhimurium). Differential
      expression analysis from the whole blood of pigs over a 7-day period following S.
      Typhimurium challenge identified 50 miRNAs, many of which are implicated in
      functional pathways associated with NF-kappaB signaling and apoptosis (e.g., ssc
      let-7c, ssc-miR-21). Transcriptional analyses of whole blood mRNA identified the
      differential expression of several genes involved in NF-kappaB signaling and
      apoptosis (e.g., IL10, CBX4, TGFB2) whose mRNAs are predicted targets of miRNAs
      identified in our study. Overall, our data identified porcine miRNAs that are
      differentially expressed following S. Typhimurium challenge, thereby defining
      regulatory factors to target for controlling the porcine response to this human
      foodborne pathogen.

PMID- 30099025
TI  - Transcriptional analysis identifies major pathways as response components to
      Sporisorium scitamineum stress in sugarcane.
AB  - BACKGROUND: Sugarcane smut, which is caused by Sporisorium scitamineum, is a
      severe fungal disease affecting sugarcane. However, the major pathways involved
      in the interaction between sugarcane and S. scitamineum remains unclear. RESULTS:
      In the present study, suppression subtractive hybridization (SSH) library
      construction, together with reverse northern blotting, was conducted on the most
      prevalent sugarcane genotype ROC22 challenged with S. scitamineum. After
      alignment and homologous expressed sequence tag (EST) assembly, a total of 155
      differentially expressed unigenes were identified from SSH libraries. Totally, 26
      of 155 differentially expressed unigenes were analyzed by qRT-PCR in sugarcane
      smut-resistant genotype YC05-179 and susceptible genotype ROC22. Genes encoded
      two unknown protein (Q1 and Q11), serine/threonine kinase (Q2), fiber protein
      (Q3), eukaryotic translation initiation factor 5A (Q23), and Sc14-3-3-like
      protein (Q24) were induced in sugarcane smut-resistant genotype YC05-179 but
      inhibited in susceptible genotype ROC22. Based on the differential expression
      data achieved from SSH libraries and qRT-PCR, we found that, serine/threonine
      kinases, Ca2+ sensors, mitogen-activated protein genes and some NBS-LRR genes may
      involve in the signal recognition and transduction of smut fungus infection in
      sugarcane. While in the plant hormone signaling pathways, the genes related to
      auxin, abscisic acid, salicylic acid and ethylene were more apparently in
      response to smut fungus invasion. The hypersensitive response, protein
      metabolism, polyamine synthesis, and cell wall formation may play an important
      role in sugarcane defense against smut fungus colonization. Additionally, the
      Sc14-3-3 might serve as a molecular modulator in sugarcane being immune to smut
      disease by interacting with proteins like ScGAPN (Q10), which have been further
      verified by BiFC assay. CONCLUSIONS: The findings of the present study could
      provide a general view about gene pathways involving in sugarcane defense against
      smut disease and facilitate a better understanding of the molecular mechanism
      underlying sugarcane-S. scitamineum interaction.

PMID- 30099027
TI  - Translocation of Exogenous FGF1 and FGF2 Protects the Cell against Apoptosis
      Independently of Receptor Activation.
AB  - FGF1 and FGF2 bind to specific cell-surface tyrosine kinase receptors (FGFRs) and
      activate intracellular signaling that leads to proliferation, migration or
      differentiation of many cell types. Besides this classical mode of action, under
      stress conditions, FGF1 and FGF2 are translocated in a receptor-dependent manner
      via the endosomal membrane into the cytosol and nucleus of the cell. However,
      despite many years of research, the role of translocated FGF1 and FGF2 inside the
      cell remains unclear. Here, we reveal an anti-apoptotic activity of intracellular
      FGF1 and FGF2, which is independent of FGFR activation and downstream signaling.
      We observed an inhibition of cell apoptosis induced by serum starvation or
      staurosporine upon treatment with exogenous FGF1 or FGF2, despite the presence of
      highly potent FGFR inhibitors. Similar results were found when the tyrosine
      kinase of FGFR1 was completely blocked by a specific mutation. Moreover, the anti
      apoptotic effect of the growth factors was abolished by known inhibitors of the
      translocation of FGF1 and FGF2 from the endosomes to the interior of the cell.
      Interestingly, FGF2 showed higher anti-apoptotic activity than FGF1. Since FGF2
      is not phosphorylated by PKCdelta and is present inside the nucleus longer than
      is FGF1, we speculated that the different activities could reflect their diverse
      nuclear export kinetics. Indeed, we observed that FGF1 mutations preventing
      binding to nucleolin and therefore phosphorylation in the nucleus affect the anti
      apoptotic activity of FGF1. Taken together, our data indicate that the
      translocation of FGF1 and FGF2 protects cells against apoptosis and promotes cell
      survival.

PMID- 30099026
TI  - Multiple Modes of Protein-Protein Interactions Promote RNP Granule Assembly.
AB  - Eukaryotic cells are known to contain a wide variety of RNA-protein assemblies,
      collectively referred to as RNP granules. RNP granules form from a combination of
      RNA-RNA, protein-RNA, and protein-protein interactions. In addition, RNP granules
      are enriched in proteins with intrinsically disordered regions (IDRs), which are
      frequently appended to a well-folded domain of the same protein. This structural
      organization of RNP granule components allows for a diverse set of protein
      protein interactions including traditional structured interactions between well
      folded domains, interactions of short linear motifs in IDRs with the surface of
      well-folded domains, interactions of short motifs within IDRs that weakly
      interact with related motifs, and weak interactions involving at most transient
      ordering of IDRs and folded domains with other components. In addition, both well
      folded domains and IDRs in granule components frequently interact with RNA and
      thereby can contribute to RNP granule assembly. We discuss the contribution of
      these interactions to liquid-liquid phase separation and the possible role of
      phase separation in the assembly of RNP granules. We expect that these principles
      also apply to other non-membrane bound organelles and large assemblies in the
      cell.

PMID- 30099029
TI  - Body composition, biochemical, behavioral and molecular alterations in overfed
      rats after chronic exposure to SSRI.
AB  - Serotonin (5-HT) plays a regulatory role in coordinating the neural circuits
      regulating energy balance, with differences in both 5-HT availability at the
      synapse and the activity of 5-HT receptors mediating anorectic (via POMC/CART
      activation) and orexigenic (via NPY/AgRP activation) responses. In conditions of
      overweight and obesity the control of energy balance is clearly deregulated, and
      serotonergic modulation appears to make a significant contribution to weight
      gain. Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) that
      increases 5-HT availability in the synaptic cleft may thus have potential effects
      on energy balance. Our aim was to use an overfeeding model to investigate the
      effects of chronic FLX treatment on energy balance-related parameters regulated
      by hypothalamic neuropeptides. Nursing male Wistar rats were assigned to normofed
      (9 pups/dam) or overfed (3 pups/dam) groups beginning at 3 days of age and
      continuing until 21 days of age, when commercial chow and water were made
      available ad libitum until experimental treatments were begun. From 39 through 59
      days of age groups were divided according to pharmacological treatment: 1) NV
      group, normofed + vehicle solution (NaCl 0.9%, 10 ml/kg b.w.), 2) NF group,
      normofed + FLX (10 mg/kg b.w., in vehicle solution, 10 ml/kg b.w.) 3), OV,
      overfed + vehicle solution and 4) OF, overfed + FLX. At 60 days of age, body
      weight, white and brown adipose tissue content, and food intake were determined,
      and serum biochemical parameters and hypothalamic neuropeptide gene expression
      were measured. Results showed that FLX induced reductions in several murinometric
      indices, improvement of adipose profile, hypophagic behavior, reduction in serum
      parameters, and positive modulation of hypophagia-related genes. These data
      suggest that the beneficial effects of FLX-treatment on overfeeding-induced
      physical and behavioral effects in rats was due to hypothalamic alterations that
      led to improvement in energy balance in animals with a compromised metabolism.

PMID- 30099030
TI  - Neural correlates of liraglutide effects in persons at risk for Alzheimer's
      disease.
AB  - : Insulin resistance (IR) is a metabolic state preceding development of type 2
      diabetes (DM2), cardiovascular disease, and neurodegenerative disorders,
      including Alzheimer's Disease (AD). Liraglutide, a glucagon-like peptide-1 (GLP)
      agonist, is an insulin-sensitizing agent with neuroprotective properties, as
      shown in animal studies. The purpose of this double-blinded, placebo-controlled
      study was to examine the neural effects of administration of liraglutide in
      cognitively normal late middle-aged individuals with subjective cognitive
      complaints (half of subjects had family history of AD). Seed-based resting state
      connectivity using functional magnetic resonance imaging (fMRI) was conducted
      before and after 12 weeks of liraglutide treatment or placebo. Neuropsychological
      testing was conducted before and after treatment to determine whether there were
      any potential behavioral correlates to neural changes. RESULTS: At baseline (time
      point 1), higher fasting plasma glucose (FPG) was associated with decreased
      connectivity between bilateral hippocampal and anterior medial frontal
      structures. At time point 2, we observed significant improvement in intrinsic
      connectivity within the default mode network (DMN) in the active group relative
      to placebo. There were no detectable cognitive differences between study groups
      after this duration of treatment. To our knowledge, this is the first placebo
      controlled study to report neural effects of liraglutide in a middle-aged
      population with subjective cognitive complaints. Larger and longer duration
      studies are warranted to determine whether liraglutide has neuroprotective
      benefits in individuals at risk for AD.

PMID- 30099031
TI  - Evidence of degradation of hair corticosterone in museum specimens.
AB  - Researchers increasingly rely on non-invasive physiological indices, such as
      glucocorticoid (GC) levels, to interpret how vertebrates respond to changes in
      their environment. Recently, hair GCs have been of particular interest, because
      they are presumed stable over long periods of storage, which may facilitate the
      study of large-scale spatial and temporal patterns of stress in mammals. In the
      current study, we evaluated the stability of hair corticosterone levels in museum
      specimens, and the potential effects of different museum curation treatments.
      Using deer mouse (Peromyscus maniculatus) specimens collected from Vancouver
      Island (11 sites, 82 individuals) over 76 years, we found that specimens
      collected earlier in the 20th century had lower hair corticosterone than more
      recently collected specimens. These results suggest that hair hormone levels may
      not be stable over decades of storage time. We then subjected hair samples
      collected from white-footed mouse (Peromyscus leucopus, n = 36) to 3 different
      museum curation treatments, and found that borax lowered hair corticosterone
      levels relative to control samples, but air drying samples, or treating them with
      turpentine had no effect. Our results present a source of concern for the use of
      museum specimens for hair hormone analysis, and for studying long term trends in
      glucocorticoid levels.

PMID- 30099032
TI  - Expression profiles of RA synthases and catabolic enzymes in newly hatched and
      metamorphosing larvae of Japanese flounder, Paralichthys olivaceus.
AB  - Retinoic acid (RA) plays various embryogenesis and post-embryogenesis roles in
      vertebrates. As exposure of metamorphosing flounder larvae to RA has teratogenic
      effects on skin color and vertebral column development, harmonized RA synthesis
      and catabolism are likely essential in metamorphic development. To approach
      understanding of the roles of RA in flounder metamorphic development, we here
      examined the tissue mRNA expression of RA synthases (aldh1a1, aldh1a2, aldh1a3)
      and catabolic enzymes (cyp26a1, cyp26b1, cyp26c1) in newly hatched and
      metamorphosing larvae, and three-month-old juveniles by in situ hybridization
      (ISH). No ISH signal was detected for any genes from the skin and vertebral
      column susceptible to the teratogenic effects by RA. Since the intestine
      expressed aldh1a2 at high level in larvae but not in juvenile, it is a
      possibility that the larval intestine serves as a source of RA, and RA catabolic
      enzymes function at the level below sensitivity of ISH at vertebral column and
      skin development. We found that aldh1a2 and aldh1a3 were expressed along the
      margin of the tectum and the neurohypophysis of pituitary, respectively, both in
      contact with the cerebrospinal fluid (CSF), and cyp26b1 at the posterior tectum
      and cerebellum. We hypothesize that RA is supplied from the tectum and pituitary
      via the CSF for brain growth and maintenance, and cyp26b1 locally regulates RA
      contents in the brain.

PMID- 30099028
TI  - Who's In and Who's Out-Compositional Control of Biomolecular Condensates.
AB  - Biomolecular condensates are two- and three-dimensional compartments in
      eukaryotic cells that concentrate specific collections of molecules without an
      encapsulating membrane. Many condensates behave as dynamic liquids and appear to
      form through liquid-liquid phase separation driven by weak, multivalent
      interactions between macromolecules. In this review, we discuss current models
      and data regarding the control of condensate composition, and we describe our
      current understanding of the composition of representative condensates including
      PML nuclear bodies, P-bodies, stress granules, the nucleolus, and two-dimensional
      membrane localized LAT and nephrin clusters. Specific interactions, such as
      interactions between modular binding domains, weaker interactions between
      intrinsically disorder regions and nucleic acid base pairing, and nonspecific
      interactions, such as electrostatic interactions and hydrophobic interactions,
      influence condensate composition. Understanding how specific condensate
      composition is determined is essential to understanding condensates as
      biochemical entities and ultimately discerning their cellular and organismic
      functions.

PMID- 30099033
TI  - Prenatal undernutrition suppresses sexual behavior in female rats.
AB  - Infectious, psychological and metabolic stresses in the prenatal and early
      neonatal period induce long-lasting effects in physiological function and
      increase the risk of metabolic disorders later in life. We examined the sexual
      behavior of female rats that were subjected to undernutrition in the prenatal
      period. Eight pregnant rats were divided into two groups: a maternal normal
      nutrition group (mNN; n = 4) and a maternal undernutrition group (mUN; n = 4),
      which received 50% of the daily food intake amount of the mNN group from
      gestation day 13 to delivery. Nine and seven female offspring were randomly
      selected from the mNN and mUN groups, respectively. Vaginal opening (VO), estrous
      cycle length, sexual behavior and mRNA expression levels of the factors that
      regulate sexual behavior were observed. In the mUN group, VO day was later, the
      estrous cycle was longer, and the lordosis quotient and lordosis rating were
      lower than in the mNN group; such differences were not seen in other sexual
      performances, such as ear wiggles, darts, kick bouts and box. The hypothalamic
      mRNA expression level of progesterone receptor (PR) A + B and oxytocin (OT) were
      significantly lower in the mUN group than in the mNN group. These findings
      indicated that prenatal undernutrition disrupted puberty onset, the estrous
      cycle, sexual behavior and hypothalamic mRNA expression of PR and OT in female
      rat pups.

PMID- 30099034
TI  - Endocrine-immune signaling as a predictor of survival: A prospective study in
      developing songbird chicks.
AB  - Immune function varies with an animal's endocrine physiology and energy reserves,
      as well as its abiotic and biotic environment. This context-dependency is thought
      to relate to adaptive trade-off resolution that varies from one context to the
      next; however, it is less clear how state- and environmentally-dependent
      differences in endocrine-immune signaling relate to survival in natural
      populations. We begin to address this question in a prospective study on a free
      living passerine bird, the tree swallow (Tachycineta bicolor), by capitalizing
      upon naturally-occurring variation in ectoparasitism in 12-day old chicks. We
      measured body mass, hematological gene expression of the pro-inflammatory
      cytokine interleukin-6 (IL-6) as well as corticosterone (CORT) secretion at
      baseline and in response to 30 min of handling. We found that chicks with
      ectoparasites had smaller body mass and higher levels of IL-6 gene expression at
      this critical stage of post-natal growth and development. Mass and IL-6 were
      positively correlated, but only among parasitized chicks, suggesting that larger
      chicks mount stronger immune responses when necessary, i.e. in the presence of
      ectoparasites that are known to induce inflammation. IL-6 mRNA expression was
      negatively correlated with stress-induced CORT levels, suggesting that this proxy
      of inflammation may be co-regulated with or coordinated by glucocorticoids. More
      importantly, these endocrine-immune parameters predicted survival to fledging,
      which was positively associated with IL-6 mRNA abundance and, to a lesser degree,
      CORT reactivity. These results suggest a link between endocrine-immune
      interactions and performance in nature, and as a consequence, they shed light on
      the potentially adaptive, context-dependent interplay between body mass,
      immunity, and endocrine physiology during development.

PMID- 30099035
TI  - Conjunctival and Intrascleral Vasculatures Assessed Using Anterior Segment
      Optical Coherence Tomography Angiography in Normal Eyes.
AB  - PURPOSE: To investigate conjunctival and intrascleral vasculatures using anterior
      segment optical coherence tomography angiography (AS-OCTA) in normal eyes.
      DESIGN: Cross-sectional study. METHODS: AS-OCTA images of the corneal limbus were
      acquired circumferentially using a swept-source optical coherence tomography
      system in 10 eyes of 10 healthy subjects. AS-OCTA flow patterns with en face
      maximum projection were compared between the superficial (from the conjunctival
      epithelium to a depth of 200 MUm) and deep (from a depth of 200 MUm to 1000 MUm)
      layers. The OCTA images were also compared with fluorescein scleral angiography
      and indocyanine green aqueous angiography images. Quantitative parameters (vessel
      density, vessel length density, vessel diameter index, and fractal dimension)
      were compared among different locations. RESULTS: The OCTA vessel patterns
      differed between the superficial and deep layers. The superficial-layer flow
      signals showed centrifugal patterns from the limbus, whereas the deep-layer flow
      signals showed segmental patterns. The OCTA en face images with whole signals had
      a similar appearance to the scleral angiography images, whereas those in the deep
      layer showed a similar appearance to the aqueous angiography images. In the
      superficial layer, only the vessel diameter index was significantly different
      among the locations (P = .003). In the deep layer, all 4 parameters differed
      significantly among the locations (P < .001 to P = .003). CONCLUSIONS: OCTA is a
      promising tool for evaluating conjunctival and intrascleral vasculatures. It may
      also help in understanding ocular surface blood flow relevant to vascular and
      ocular surface diseases, as well as aqueous humor outflow.

PMID- 30099036
TI  - Combined Use of Retinal Nerve Fiber Layer and Ganglion Cell-Inner Plexiform Layer
      Event-based Progression Analysis.
AB  - PURPOSE: To evaluate patterns of glaucomatous structural progression using the
      combined retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer
      (GCIPL) event-based progression analysis feature provided by spectral-domain
      optical coherence tomography (SD-OCT)'s - (GPA) software. DESIGN: Retrospective
      observational case series. METHODS: Seventy-nine (79) patients were identified
      with open-angle glaucoma (OAG) showing clinically confirmed structural
      progression within a minimum 3-year follow-up period. For each eye, RNFL and
      GCIPL GPA data were obtained from serial SD-OCT data from 2012 to 2017. An
      integrated GPA map thereafter was merged by vascular landmark-guided
      superimposition of RNFL and GCIPL GPA event-based progression maps onto the RNFL
      imagery (resulting in what we call the GPA PanoMap). The GPA PanoMap progression
      patterns were classified as (1) RNFL-only, (2) GCIPL-only, (3) concurrent (both
      RNFL and GCIPL), (4) GCIPL after RNFL, and (5) RNFL after GCIPL. The locations of
      structural progression were classified, based on an earlier schematic model, as
      (1) superior vulnerability zone (SVZ), (2) papillomacular bundle (PM), (3)
      macular vulnerability zone (MVZ), and (4) inferoinferior portion. Structural
      progression patterns on the GPA PanoMap were evaluated according to the location
      of progression. Among the eyes with progression in the inferior hemiretina,
      structural progression patterns on the GPA PanoMap were evaluated according to
      the baseline structural damage. RESULTS: On the GPA PanoMap, when structural
      progression was located in the SVZ or inferoinferior portion, it was detected
      only in the RNFL area; when progression was located in the PM or MVZ, various
      patterns were observed, among which the concurrent pattern was the majority in
      both areas (43.8% and 45.6% in the PM and MVZ, respectively). Among the eyes with
      progression in the inferior hemiretina (n = 66), the location of progression
      varied but did not differ significantly according to the baseline deviation map
      (P = .440). The progression patterns of MVZ were significantly different among
      the baseline deviation map patterns (P = .023); however, all of the progression
      patterns of the inferoinferior portion were RNFL-only. CONCLUSION: The various
      progression patterns were confirmed according to the locations and baseline
      patterns of glaucomatous structural change on the integrated GPA map (GPA
      PanoMap). Combined use of RNFL and GCIPL GPA or the GPA PanoMap could be useful
      for determination of structural progression and understanding of its patterns in
      patients with glaucoma.

PMID- 30099038
TI  - Hyaluronic acid is present on specific perineuronal nets in the mouse cerebral
      cortex.
AB  - In the central nervous system (CNS), extracellular matrix (ECM) molecules
      comprise more than 20% of the volume and are involved in neuronal plasticity,
      synaptic transmission, and differentiation. Perineuronal nets (PNNs) are ECM
      molecules that highly accumulate around the soma of neurons. The components of
      the ECM in the CNS include proteins, proteoglycans, and glycosaminoglycans.
      Although hyaluronic acid (HA) is considered a constituent element of PNNs, the
      distribution of HA in the cortex has not been clarified. To elucidate the
      cortical region-specific distribution of HA, we quantitatively analyzed HA
      binding protein (HABP)-positive PNNs in the mature mouse cerebral cortex. Our
      findings revealed that HABP-positive PNNs are present throughout the mouse
      cortex. The distribution of many HABP-positive PNNs differed from that of
      Wisteria floribunda agglutinin-positive PNNs. Furthermore, we observed granular
      like HABP-positive PNNs in layer 1 of the cortex. These findings indicate that
      PNNs in the mouse cortex show region-dependent differences in composition. HABP
      positive PNNs in layer 1 of the cortex may have different functions such as
      neuronal differentiation, proliferation, and migration unlike what has been
      reported for PNNs so far.

PMID- 30099037
TI  - Performance of the 10-2 and 24-2 Visual Field Tests for Detecting Central Visual
      Field Abnormalities in Glaucoma.
AB  - PURPOSE: To compare the performance of the pattern standard deviation (PSD)
      values derived from the central 12 locations of the 24-2 visual field test (C24
      2) to the entire 10-2 test for detecting central visual field abnormalities in
      eyes with, suspected of having, or at risk of having glaucoma. DESIGN: Cross
      sectional case-control study. METHODS: Eyes with, suspected of having, or at risk
      of having glaucoma, based on masked grading of optic disc stereophotographs
      and/or ocular hypertension (intraocular pressure >= 22 mm Hg) were included as
      cases (n = 523). Eyes from healthy participants were included as controls (n =
      107) to allow the 2 tests to be compared at matched specificities. The
      sensitivity to detect cases at 95% specificity using PSD values derived from the
      entire 10-2 test and C24-2 were compared. RESULTS: The sensitivity of the 10-2
      and C24-2 PSD values was not significantly different between the 10-2 and C24-2
      at matched specificities (35.9% and 35.4% respectively; P = .900). There was also
      a substantial agreement between the cases detected by both methods (kappa = 0.80
      +/- 0.04), and a very strong association between the PSD values from the 2
      methods (R2 = 0.91). CONCLUSIONS: 10-2 and 24-2 tests identified a similar number
      of eyes with, suspected of having, or at risk of having glaucoma as having
      central visual field abnormalities using PSD values. These findings do not mean
      that 10-2 tests are not useful, but highlight the need for further studies to
      determine the potential advantages of 10-2 tests through equivalent comparisons
      against 24-2 tests to ensure appropriate recommendations are made about its
      incorporation into the glaucoma standard of care.

PMID- 30099040
TI  - Exploring the effects of methylene blue on amyloid fibrillogenesis of lysozyme.
AB  - The 129-residue lysozyme has been shown to form amyloid fibrils in vitro. While
      methylene blue (MB), a compound in the phenothiazinium family, has been shown to
      dissemble tau fibril formation, its anti-fibrillogenic effect has not been
      thoroughly characterized in other proteins/peptides. This study examines the
      effects of MB on the in vitro fibrillogenesis of lysozyme at pH 2.0 and 55 
      degrees C. Our results demonstrated that, upon 7-day incubation, the plateau ThT
      fluorescence of the sample was found to be ~8.69% or ~2.98% of the control when
      the molar ratio of lysozyme to MB was at 1:1.11 or 1:3.33, respectively,
      indicating that the inhibitory potency of MB against lysozyme fibrillogenesis is
      positively correlated with its concentration. We also found that MB is able to
      destabilize the preformed lysozyme fibrils. Moreover, molecular docking and
      molecular dynamics simulations results revealed that MB's mechanism of fibril
      formation inhibition may be triggered by binding with lysozyme's aggregation
      prone region. Results reported here provide solid support for MB's effect on
      amyloid fibrillogenesis. We believe the additional insights gained herein may
      pave way to the discovery of other small molecules that may have similar action
      toward amyloid fibril formation and its associated diseases.

PMID- 30099039
TI  - Identification of novel blood biomarker panels to detect ischemic stroke in
      patients and their responsiveness to therapeutic intervention.
AB  - The use of blood biomarkers for stroke has been long considered an excellent
      method to determine the occurrence, timing, subtype, and severity of stroke. In
      this study, venous blood was obtained from ischemic stroke patients after stroke
      onset and compared with age and sex-matched controls. We used a multiplex panel
      of 37 inflammatory molecules, analyzed using Luminex MagPix technology, to
      identify the changes in plasma proteins after ischemic stroke. We identified
      eight key molecules that were altered within the blood of stroke patients as
      compared to controls. Plasma levels of interleukin 6 signal transducer (sIL
      6Rbeta/gp130), matrix metalloproteinase-2 (MMP-2), osteopontin, sTNF-R1 and sTNF
      R2 were significantly higher in stroke patients compared to controls. Interferon
      beta, interleukin-28, and thymic stromal lymphopoietin (TSLP) were decreased in
      plasma from stroke patients. No other immunological markers were significantly
      different between patient groups. When stroke patients were treated with tissue
      plasminogen activator (t-PA), plasma levels of interferon-alpha2 significantly
      increased while interleukin-2 and pentraxin-3 decreased. The discriminatory power
      of the molecules was evaluated by receiver operating characteristic (ROC)
      analysis. According to ROC analysis, the best markers for distinguishing stroke
      occurrence were MMP-2 (AUC = 0.76, sensitivity 62.5%, specificity 88.5%), sTNF-R2
      (AUC = 0.75, sensitivity 83.3%, specificity 65.3%) and TSLP (AUC = 0.81,
      sensitivity 66.7%, specificity 96.2%). Multivariate logistic regression, used to
      evaluate the combination of proteins, identified a biomarker panel with high
      specificity and sensitivity (AUC = 0.96, sensitivity 87.5%, specificity 96.2%).
      These results indicate a novel set of blood biomarkers that could be used in a
      panel to identify stroke patients and their responsiveness to therapeutic
      intervention.

PMID- 30099041
TI  - Fire-retardant multilayer assembled on polyester fabric from water-soluble
      chitosan, sodium alginate and divalent metal ion.
AB  - Lay-by-layer (LbL) assembly among water-soluble chitosan (WSC), sodium alginate
      (SA) and copper ion was applied to form polysaccharide-based flame retardant
      coating on polyester fabric. Thermogravimetric analysis (TGA) results indicated
      the thermal decomposition temperature of the surface-modified sample was higher
      than that of the original one, and increased with increasing the layers.
      Microscale combustion calorimetry (MCC) measurements exhibited that the heat
      release rate (HRR) values of the samples containing various layers were lower
      than that of unmodified sample and decreased as increasing layers. The peak value
      in HRR and total heat release of unmodified sample were 343.31 w/g and 46.11
      kJ/g, while 214.29 w/g and 38.49 kJ/g for the sample containing 16-layers WSC-SA
      Cu(II) respectively. The limiting oxygen index values of the samples were in the
      order: samples containing WSC-SA-Cu(II) layers > samples containing SA-Cu(II)
      layers > unmodified sample. The vertical burning reflected the sample containing
      WSC-SA-Cu(II) or SA-Cu(II) self-extinguished within 35 s, and the time was
      shorter as the sample composed of more layers. The flame retardancy of polyester
      fabric was significantly improved through LbL assembly of polysaccharide-based
      polyelectrolytes and copper ion.

PMID- 30099042
TI  - Isolation, characterization, and microwave assisted surface modification of
      Colocasia esculenta (L.) Schott mucilage by grafting polylactide.
AB  - Mucilage (represented as CEM) is abundantly present in Colocasia esculenta (L.)
      Schott or taro and is a water-soluble neutral polysaccharide that can act as a
      binder, thickening agent, and matrix agent in the pharmaceutical fields of
      research. Presence of hydroxyl groups on its surface structure allows chemical
      modification. This study describes in details the synthesis and characterization
      of its graft copolymer with polylactide (CEM-g-PLA). The polymerization has
      performed using both the microwave irradiation and conventional methods. Ring
      opening polymerization of lactide onto the mucilage carried out in presence of
      stannous octoate as catalyst in chloroform medium produced CEM-g-PLA copolymer
      under optimum condition. The structure of CEM-g-PLA copolymers obtained from both
      the methods were comprehensively characterized for their physicochemical and
      thermal properties by Fourier transform infrared spectroscopy (FTIR), scanning
      electron microscopy (SEM), and X-ray diffraction (XRD), differential scanning
      colorimetric (DSC), thermo-gravimetric analysis (TGA/DTG) and Dynamic light
      scattering (DLS) measurements. Grafting of lactide onto CEM backbone has changed
      its water absorption capacity, solubility and swelling power, morphology,
      crystalline structure, and thermal property of the mucilage. The newly
      synthesized CEM-g-PLA copolymer may find potential applications in wastewater
      treatment and for sustained and controlled drug delivery systems.

PMID- 30099043
TI  - Berberine-piperazine conjugates as potent influenza neuraminidase blocker.
AB  - In these studies, we analyzed substituted piperazine based berberine analogs
      conjugated through a pentyloxy side chain for their in vitro and in silico
      biological effects. All the final analogs were screened for their in vitro
      antiviral action against a collection of different influenza virus strains using
      the CPE assay and SRB assay. Moreover, their cytotoxicity towards non-cancer cell
      lines was examined employing Madin-Darby canine kidney (MDCK) cell lines. The
      anti-influenza activities of berberine-piperazine derivatives (BPD) were
      evaluated in the range from 35.16 MUg/mL to 90.25 MUg/mL of the IC50s along with
      cytotoxicity level which was observed in the range 44.8 MUg/mL to 3890.6 MUg/mL
      of CC50s towards MDCK cells. In an effort to know the mechanism of action of BPD1
      BPD23, results of Neuraminidase inhibition assay and Molecular docking studies
      carried out against neuraminidase as the target enzyme revealed that titled
      compounds are potential neuraminidase inhibitors that merge to the active site of
      neuraminidase, with moderate to high binding energy.

PMID- 30099044
TI  - Long non-coding RNA GAS5 reduces cardiomyocyte apoptosis induced by MI through
      sema3a.
AB  - OBJECTIVE: To investigate the role of GAS5 on cardiomyocyte apoptosis. METHODS:
      Myocardial infarction (MI) model was established by the left-anterior descending
      coronary artery ligation. Norepinephrine (NE) was used to induce cardiomyocyte
      apoptosis. GAS5 levels and mRNA expressions of Semaphorin 3a (sema3a) were
      measured by qRT-PCR. Protein level of sema3a was detected by Western blotting.
      Cardiomyocyte apoptosis was detected by flow cytometry assay. RNA pull-down and
      RIP assay were used to verify the combination between GAS5 and sema3a. Infarct
      size was measured by TTC staining. RESULTS: GAS5 expression was increased in
      infarct boundary zone of MI group, while sema3a protein expression was decreased.
      Moreover, GAS5 expression in cardiomyocyte induced by NE was higher than control
      group, while sema3a protein expression was lower than control group. In addition,
      GAS5 could negatively regulate sema3a protein expression. pcDNA-GAS5 reversed
      cardiomyocyte apoptosis induced by NE, while pcDNA-sema3a countered the
      inhibitory effect. In animal experiment, overexpression of GAS5 decreased sema3a
      protein expression and reduced infarct size. CONCLUSION: GAS5 could ameliorate
      cardiomyocyte apoptosis induced by MI via down-regulating sema3a.

PMID- 30099045
TI  - Lipid storage myopathies: Current treatments and future directions.
AB  - Lipid storage myopathies (LSMs) are a heterogeneous group of genetic disorders
      that present with abnormal lipid storage in multiple body organs, typically
      muscle. Patients can clinically present with cardiomyopathy, skeletal muscle
      weakness, myalgia, and extreme fatigue. An early diagnosis is crucial, as some
      LSMs can be managed by simple nutraceutical supplementation. For example, high
      dosage l-carnitine is an effective intervention for patients with Primary
      Carnitine Deficiency (PCD). This review discusses the clinical features and
      management practices of PCD as well as Neutral Lipid Storage Disease (NLSD) and
      Multiple Acyl-CoA Dehydrogenase Deficiency (MADD). We provide a detailed summary
      of current clinical management strategies, highlighting issues of high-risk
      contraindicated treatments with case study examples not previously reviewed.
      Additionally, we outline current preclinical studies providing disease
      mechanistic insight. Lastly, we propose that a number of other conditions
      involving lipid metabolic dysfunction that are not classified as LSMs may share
      common features. These include Neurofibromatosis Type 1 (NF1) and autoimmune
      myopathies, including Polymyositis (PM), Dermatomyositis (DM), and Inclusion Body
      Myositis (IBM).

PMID- 30099046
TI  - Prevalence of master plans supportive of active living in US municipalities.
AB  - Community planning documents can play an important role in promoting the design
      and maintenance of walkable communities. This study estimates the prevalence
      among US municipalities of (1) community wide planning documents and (2)
      inclusion of plan objectives supportive of active living within these documents.
      Data from the 2014 National Survey of Community-Based Policy and Environmental
      Supports for Healthy Eating and Active Living (CBS HEAL), a survey of local
      officials, were analyzed (n = 2005). Prevalence of comprehensive or general
      plans, 3 specific plan types, and 3 objectives supportive of active living were
      analyzed using survey weights to create national estimates. Overall, 64% of
      municipalities had a comprehensive/general plan, 46% had a transportation plan,
      48% had a bicycle or pedestrian plan and 76% had a land use plan. Of
      municipalities with a plan, 78% included at least one of the three objectives
      measured supportive of active living. Differences in presence of plans and
      objectives were observed by population size of the municipality, urban status,
      region, and median education. Helping communities, especially smaller or rural
      municipalities and those with lower median education levels, create and adopt
      planning documents supportive of active living may be an important step in
      creating more walkable communities.

PMID- 30099047
TI  - Breast cancer screening programme participation and socioeconomic deprivation in
      France.
AB  - The objective was to quantify the relationship between deprivation and national
      breast cancer screening programme (NBCSP) participation at an ecological level in
      mainland France. Data from 4,805,390 women-living in 36,209 municipalities within
      95 departments-participating in the 2013-2014 NBCSP were analysed using the
      French Deprivation Index (FDep). FDep population quintiles by municipality were
      computed to describe NBCSP participation according to deprivation. To better
      examine the relationship between continuous value of deprivation index and
      participation rates at the municipality level, we built a generalized linear
      mixed model. Geographical variations in participation rates were marked. The
      national standardized participation rate was higher in the intermediate quintiles
      (55%), 45% for the least deprived one and 52% for the most deprived one. Using
      our model, we also obtained an inverted U-curve for the relationship between
      NBCSP participation and municipality deprivation: participation was lower for
      both the least and most deprived municipalities. This relationship was also
      observed for each of the two subpopulations-urban municipalities and rural ones
      considered separately. Introducing the FDep in the model reduced slightly the
      unexplained variations in participation rates between departments and between
      municipalities (with a proportional change in variance of 14% and 12%
      respectively). We highlight major disparities in departmental participation rates
      and FDep/participation profiles. However, deprivation appears to have only little
      influence on geographical variation in participation rates. There is a need to
      further understand the factors affecting geographical variation in participation
      rates, in particular the use of opportunistic screening.

PMID- 30099048
TI  - Association of serum Sestrin2 level with metabolic risk factors in newly
      diagnosed drug-naive type 2 diabetes.
AB  - AIMS: Previous in-vitro and in-vivo experimental studies have shown that Sestrin2
      attenuates oxidative stress and the pro-inflammatory pathway, resulting in
      improving metabolic homeostasis. However, the relationship between circulating
      Sestrin2 concentration and cardiometabolic risks in humans has not been explored.
      METHODS: Sestrin2 concentration was measured in 240 subjects (46 without diabetes
      and 194 with diabetes), and the associations between Sestrin2 level and various
      cardiometabolic risk factors including body composition, insulin resistance, and
      atherosclerosis was assessed. RESULTS: Sestrin2 concentration showed a trend of
      increasing in subjects with metabolic syndrome. After adjustment for age and
      gender, Sestrin2 level had a positive relationship with serum triglyceride,
      alanine aminotransferase (ALT), and creatinine levels, but no association with
      carotid atherosclerosis. Especially, in subjects with type 2 diabetes Sestrin2
      concentration exhibited a significant positive correlation with body mass index
      (P = 0.015), waist circumference (P = 0.020), high-sensitivity C-reactive protein
      (P = 0.008), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (P =
      0.041), percentage body fat (P = 0.001), and truncal fat mass (P = 0.005) after
      adjusting age and gender. Multiple stepwise regression analysis identified age,
      serum ALT and creatinine levels, and percentage body fat as independent
      determining factors for Sestrin2 concentration in patients with type 2 diabetes
      (R2 = 0.173). CONCLUSIONS: This study is the first to demonstrate a trend for
      increased Sestrin2 level in subjects with metabolic syndrome. In particular, in
      subjects with type 2 diabetes, Sestrin2 was significantly related to insulin
      resistance and percentage body fat, suggesting its potential as a novel
      modulatory factor for metabolic disorders in humans.

PMID- 30099049
TI  - 7-Methoxyderivative of tacrine is a 'foot-in-the-door' open-channel blocker of
      GluN1/GluN2 and GluN1/GluN3 NMDA receptors with neuroprotective activity in vivo.
AB  - N-methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that
      mediate excitatory neurotransmission in the mammalian central nervous system
      (CNS), and their dysregulation results in the aetiology of many CNS syndromes.
      Several NMDAR modulators have been used successfully in clinical trials
      (including memantine) and NMDARs remain a promising pharmacological target for
      the treatment of CNS syndromes. 1,2,3,4-Tetrahydro-9-aminoacridine (tacrine; THA)
      was the first approved drug for Alzheimer's disease (AD) treatment. 7
      methoxyderivative of THA (7-MEOTA) is less toxic and showed promising results in
      patients with tardive dyskinesia. We employed electrophysiological recordings in
      HEK293 cells and rat neurones to examine the mechanism of action of THA and 7
      MEOTA at the NMDAR. We showed that both THA and 7-MEOTA are "foot-in-the-door"
      open-channel blockers of GluN1/GluN2 receptors and that 7-MEOTA is a more potent
      but slower blocker than THA. We found that the IC50 values for THA and 7-MEOTA
      exhibited the GluN1/GluN2A < GluN1/GluN2B < GluN1/GluN2C = GluN1/GluN2D
      relationship and that 7-MEOTA effectively inhibits human GluN1/GluN2A-M817V
      receptors that carry a pathogenic mutation. We also showed that 7-MEOTA is a
      "foot-in-the-door" open-channel blocker of GluN1/GluN3 receptors, although these
      receptors were not inhibited by memantine. In addition, the inhibitory potency of
      7-MEOTA at synaptic and extrasynaptic hippocampal NMDARs was similar, and 7-MEOTA
      exhibited better neuroprotective activity when compared with THA and memantine in
      rats with NMDA-induced lesions of the hippocampus. Finally, intraperitoneal
      administration of 7-MEOTA attenuated MK-801-induced hyperlocomotion and pre-pulse
      inhibition deficit in rats. We conclude that 7-MEOTA may be considered for the
      treatment of diseases associated with the dysfunction of NMDARs.

PMID- 30099050
TI  - Ouabain increases neuronal branching in hippocampus and improves spatial memory.
AB  - Previous research shows Ouabain (OUA) to bind Na, K-ATPase, thereby triggering a
      number of signaling pathways, including the transcription factors NF?B and CREB.
      These transcription factors play a key role in the regulation of BDNF and WNT
      beta-catenin signaling cascades, which are involved in neuroprotection and memory
      regulation. This study investigated the effects of OUA (10 nM) in the modulation
      of the principal signaling pathways involved in morphological plasticity and
      memory formation in the hippocampus of adult rats. The results show
      intrahippocampal injection of OUA 10 nM to activate the Wnt/beta-Catenin
      signaling pathway and to increase CREB/BDNF and NF?B levels. These effects
      contribute to important changes in the cellular microenvironment, resulting in
      enhanced levels of dendritic branching in hippocampal neurons, in association
      with an improvement in spatial reference memory and the inhibition of long-term
      memory extinction.

PMID- 30099051
TI  - Profiling of orthosteric and allosteric group-III metabotropic glutamate receptor
      ligands on various G protein-coupled receptors with Tag-lite(r) assays.
AB  - Group-III metabotropic glutamate (mGlu) receptors are important synaptic
      regulators and are potential druggable targets for Parkinson disease, autism and
      pain. Potential drugs include orthosteric agonists in the glutamate binding
      extracellular domain and positive allosteric modulators interacting with seven
      pass transmembrane domains. Orthosteric agonists are rarely completely specific
      for an individual group-III mGlu subtype. Furthermore they often fail to pass the
      blood-brain barrier and they constitutively activate their target receptor. These
      properties limit the potential therapeutic use of orthosteric agonists.
      Allosteric modulators are more specific and maintain the biological activity of
      the targeted receptor. However, they bind in a hydrophobic pocket and this limits
      their bio-availability and increases possible off-target action. It is therefore
      important to characterize the action of potential drug targets with a
      multifaceted and deeply informative assay. Here we aimed at multifaceted deep
      profiling of the effect of seven different agonists, and seven positive
      allosteric modulators on 34 different G protein-coupled receptors by a Tag
      lite(r) assay. Our results did not reveal off-target activity of mGlu orthosteric
      agonists. However, five allosteric modulators had either positive or negative
      effects on non-cognate G protein-coupled receptors. In conclusion, we demonstrate
      the power of the Tag-lite(r) assay for potential drug ligand profiling on G
      protein-coupled receptors and its potential to identify positive allosteric
      compounds.

PMID- 30099052
TI  - Negative roles of B7-H3 and B7-H4 in the microenvironment of cervical cancer.
AB  - Although persistent human papilloma virus (HPV) infection exerts a crucial
      influence on cervical carcinogenesis, other factors are also involved in its
      development, such as intraepithelial lesions and cervical cancer. B7-H3 and B7
      H4, which have been reported to be co-regulatory ligands in the B7 family, had
      been found to be overexpressed in cervical cancer and correlated with adverse
      clinicopathological features and poor prognosis in our previous studies. In this
      study, we sought to explore the effects of B7-H3 and B7-H4 on the cervical
      microenvironment. Among several immune cytokines, interleukin-10 (IL-10) and
      transforming growth factor (TGF) beta1 stand out as important immunosuppressive
      factors. Our studies found that IL-10 expression increased with pathological
      change levels and significantly correlated with cervical cancer differentiation
      (P < 0.05). TGF-beta1 correlated with lymph node metastasis (LNM) (P < 0.01).
      Expression of B7-H3 and B7-H4 positively correlated with the expression of IL-10
      and TGF-beta1. After co-culture, we found that overexpression of B7-H3 and B7-H4
      in cervical cancer cell lines resulted in activation of the cell cycle and
      decreased apoptosis of U-937 cells. In addition, the contents of IL-10 and TGF
      beta1, as well as their protein expression levels, increased in co-culture
      supernatants in U-937 cells, suggesting regulation by the p-JAK2/STAT3 pathway.
      The in vivo results demonstrated that with the increasing expression of B7-H3/B7
      H4, the expression of IL-10 and TGF-beta1 also increased significantly. Overall,
      the expression of B7-H3 and B7-H4 favored an immunosuppressive microenvironment
      by promoting the production of IL-10 and TGF-beta1, thereby resulting in
      progression of cervical carcinogenesis.

PMID- 30099053
TI  - Optimization of cationic (Q)-paper for detection of arboviruses in infected
      mosquitoes.
AB  - Previously (Glushakova et al. 2017), a cellulose-based cationic (Q) paper
      derivatized with quaternary ammonium groups was shown to be a convenient platform
      to collect, preserve, and store nucleic acids (NAs) derived from mosquito vectors
      infected with pathogens for surveillance. NAs bind electrostatically to Q-paper,
      but the quantity of NA bound depends on the paper's binding capacity. To optimize
      the original technology for mosquito surveillance, factors that affected NA
      absorbance on Q-paper were evaluated. Sixteen variations of Q-paper were prepared
      with modifications of the derivatizing reagents and derivatization temperature.
      The binding capacities of these variations were determined first with 1,3,5
      benzenetricarboxylic (BTCA), then viral RNA (purified or in infected mosquito
      samples) was used for validation. For this, samples with Zika (ZIKV) and
      chikungunya (CHIKV) RNA or virus-infected Aedes aegypti mosquito bodies were
      applied to sixteen Q-paper variants. Washing the paper samples with water versus
      elution with aqueous salt (1 M) gave samples that were analyzed for viral RNA by
      a PCR-based direct Luminex hybridization assay. The comparison ranked the Q-paper
      binding capacities from the lowest to the highest. The Q-paper with the highest
      RNA binding capability was further validated with ZIKV- and CHIKV-infected
      mosquito saliva.

PMID- 30099054
TI  - Assessment of sodium benzoate and potassium sorbate preservatives in some
      products in Kashan, Iran with estimation of human health risk.
AB  - The purpose was to assess of sodium benzoate (SB) and potassium sorbate (PS)
      preservatives in 103 samples of cake, toast bread, tomato paste, mayonnaise
      sauce, carbonated soft drink and Olovieh salad in Kashan, by spectrophotometry
      and high performance liquid chromatography (HPLC) methods. The chronic daily
      intake (CDI), target hazard quotient (THQ) and hazard index (HI) of SB and PS for
      Iranian population were calculated. The results showed that SB and PS were not
      detected in the tomato paste samples. SB and PS concentrations for all samples
      were less than regulatory limits except for PS in one cake sample (3.57%). CDI
      and THQ of PS for mayonnaise sauce, Olovieh salad and cake products, except toast
      bread, were less than the acceptable daily intakes (ADIs) and one, respectively.
      While HI value of PS for the selected products was more than one, indicating that
      the non-carcinogenic risk represent a threat to consumers. THQ and HI values of
      SB for mayonnaise sauce and carbonated soft drink products were more than one
      through consumption of these products, indicating considerable non-carcinogenic
      risk. Therefore, the results highlighted the importance of a more attentive
      monitoring of these preservatives by the public and food health authorities in
      Iran.

PMID- 30099055
TI  - Evaluation of methanol content of beverages using an easy modified chromotropic
      acid method.

PMID- 30099056
TI  - Rare mould infections caused by Mucorales, Lomentospora prolificans and Fusarium,
      in San Diego, CA: the role of antifungal combination therapy.
AB  - Non-Aspergillus invasive mould infections (IMIs) are associated with devastating
      morbidity and mortality rates and are increasingly diagnosed in immunocompromised
      hosts. The aim of this study was to describe the epidemiology and outcomes of non
      Aspergillus IMIs at a university hospital in San Diego, California, USA. A
      retrospective chart review of the medical records of all patients with cultures
      growing non-Aspergillus moulds at the microbiology laboratory in the Center for
      Academic Laboratory Medicine, Department of Pathology, University of California,
      San Diego (UCSD) Health between mid-2014 and mid-2017 (3-year period) was
      performed. A total of 23 cases of non-Aspergillus IMI were identified, including
      10 cases of mucormycosis, 8 cases of lomentosporiosis and 5 cases of fusariosis.
      Antifungal susceptibility testing was performed for 14 isolates, and 10/11
      Fusarium and Lomentospora isolates had minimum inhibitory concentrations (MICs)
      of >16 ug/mL for voriconazole and/or posaconazole. Overall 180-day mortality was
      significantly lower among those who received combination antifungal therapy than
      among those who received single-agent therapy [3/13 (23%) vs. 9/10 (90%); P =
      0.003]. In conclusion, Lomentospora prolificans (35% of non-Aspergillus IMIs) and
      Fusarium spp. (22%) accounted for high proportions of non-Aspergillus IMIs during
      the study period. Non-Aspergillus IMIs were detected in patients with various
      underlying diseases and were associated with high mortality rates, which was
      significantly lower in those who received antifungal combination therapy.

PMID- 30099057
TI  - First report of an mcr-1-harboring Salmonella enterica subsp. enterica serotype
      4,5,12:i:- strain isolated from blood of a patient in Switzerland.

PMID- 30099058
TI  - Disease Probability Index (DPI, chi): A new alignment-free scoring method to
      evaluate the propensities of polypeptide sequences leading to disease onset.
AB  - The analyses of the amino acid sequences of proteins provide valuable information
      regarding the structure and function of the protein. A comparatively new approach
      is the alignment-free sequence comparisons. To-date most, if not all, sequence
      analysis techniques are used to find out the sequence homologies to measure the
      evolutionary relatedness among the species. However, a still untouched avenue in
      the field of sequence analyses is to build a comparative estimate of the sequence
      similarities between unrelated protein sequences from and within a single
      species. In this work, we tried to develop an alignment-free scoring method to
      study sequences from different proteins belonging to humans to identify the
      disease-associations of the sequences. A total of 52 protein sequences were
      analyzed. There were 599 reported polymorphic sites and 802 (708 polymorphic and
      94 disease-associated) Single Amino acid Variants (SAVs) in the training data
      set. For cross-validation purposes, another set of 62 protein sequences (26
      enzymes, 16 Membrane-bound Enzymes and 20 Membrane-bound Proteins), with a total
      of 261 reported polymorphic sites and 799 (291 polymorphic and 508 disease
      associated) SAVs, were used. A negative correlation was observed for both
      training and cross-validation data set between percentage of reported disease
      associated SAVs with a ratio of (polymorphic site : protein length). A new
      scoring pattern was also developed that would take into account the ratio of
      polymorphic site and protein length by counting the number of polymorphic amino
      acids and the total numbers of amino acids in proteins.

PMID- 30099059
TI  - Typical readout durations in spiral cine DENSE yield blurred images and
      underestimate cardiac strains at both 3.0 T and 1.5 T.
AB  - INTRODUCTION: Displacement encoding with stimulated echoes (DENSE) is a phase
      contrast technique that encodes tissue displacement into phase images, which are
      typically processed into measures of cardiac function such as strains. For
      improved signal to noise ratio and spatiotemporal resolution, DENSE is often
      acquired with a spiral readout using an 11.1 ms readout duration. However, long
      spiral readout durations are prone to blurring due to common phenomena such as
      off-resonance and T2* decay, which may alter the resulting quantifications of
      strain. We hypothesized that longer readout durations would reduce image quality
      and underestimate cardiac strains at both 3.0 T and 1.5 T and that using short
      readout durations could overcome these limitations. MATERIAL AND METHODS:
      Computational simulations were performed to investigate the relationship between
      off-resonance and T2* decay, the spiral cine DENSE readout duration, and measured
      radial and circumferential strain. Five healthy participants subsequently
      underwent 2D spiral cine DENSE at both 3.0 T and 1.5 T with several different
      readout durations 11.1 ms and shorter. Pearson correlations were used to assess
      the relationship between cardiac strains and the spiral readout duration.
      RESULTS: Simulations demonstrated that long readout durations combined with off
      resonance and T2* decay yield blurred images and underestimate strains. With the
      typical 11.1 ms DENSE readout, blurring was present in the anterior and lateral
      left ventricular segments of participants and was markedly improved with shorter
      readout durations. Radial and circumferential strains from those segments were
      significantly correlated with the readout duration. Compared to the 1.9 ms
      readout, the 11.1 ms readout underestimated radial and circumferential strains in
      those segments at both field strengths by up to 19.6% and 1.5% (absolute), or 42%
      and 7% (relative), respectively. CONCLUSIONS: Blurring is present in spiral cine
      DENSE images acquired at both 3.0 T and 1.5 T using the typical 11.1 ms readout
      duration, which yielded substantially reduced radial strains and mildly reduced
      circumferential strains. Clinical studies using spiral cine DENSE should consider
      these limitations, while future technical advances may need to leverage
      accelerated techniques to improve the robustness and accuracy of the DENSE
      acquisition rather than focusing solely on reduced acquisition time.

PMID- 30099060
TI  - Spine MR images in patients with pedicle screw fixation: Comparison of
      conventional and SEMAC-VAT sequences at 1.5 T.
AB  - BACKGROUND AND PURPOSE: Slice-encoding metal artifact corrections (SEMAC)-view
      angle tilting (VAT) sequences have recently been used in clinical protocols to
      reduce metal artifacts in MR scans of patients with spinal instrumentation. The
      objective of this study was to compare the SEMAC-VAT sequence with the
      conventional MR sequence with a low bandwidth turbo-spin echo (TSE) in terms of
      image quality, visibility of periprosthetic structures, and diagnostic confidence
      for detection of postoperative complications in patients who underwent pedicle
      screw fixation at 1.5 T. METHODS: Seventy patients who underwent pedicle screw
      fixation between the thoracic vertebrae and the sacrum were included in the
      study. The MR scans were retrospectively evaluated by two radiologists for signal
      to-noise ratio of anatomical structures and size of artifacts, visibility of
      periprosthetic anatomical structures, and diagnostic confidence for detection of
      postoperative complications on conventional TSE and on SEMAC-VAT images. Paired t
      tests and Wilcoxon signed-rank tests were used for comparisons, and kappa values
      were used for inter-observer agreement. RESULTS: SEMAC-VAT images demonstrated
      significantly fewer metal artifacts, providing improved delineation of most
      periprosthetic anatomical structures and higher diagnostic confidence for
      detection of postoperative complications compared with conventional TSE images (p
      < 0.001). For the spinal canal, however, the visibility of anatomical structures
      and diagnostic confidence for detection of postoperative complications were
      better for conventional TSE than for SEMAC-VAT imaging (p < 0.001). CONCLUSION:
      In conclusion, although SEMAC-VAT can significantly reduce metal artifact and
      provide improved delineation of periprosthetic anatomical structures compared to
      conventional TSE images, TSE is better for spinal canal evaluation. Therefore, it
      is important to understand the advantages and disadvantages of SEMAC-VAT and to
      use it properly.

PMID- 30099061
TI  - 1alpha,25-Dihydroxyvitamin D3 inhibits aflatoxin B1-induced proliferation and
      dedifferentiation of hepatic progenitor cells by regulating PI3K/Akt and Hippo
      pathways.
AB  - Hepatic progenitor cells (HPCs) might be the origin of hepatocellular carcinoma.
      1alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) (VD3) has been documented as an
      anticancer agent for various cancers. However, the potential effect of VD3 on the
      proliferation and malignant transformation of HPCs induced by aflatoxin B1 (AFB1)
      has not been determined. In this study, we found that AFB1 exhibited the
      stimulative effects on the proliferation, dedifferentiation and invasion of HPCs
      via activating AKT pathway but turning off Hippo pathway, which were terminated
      when VD3 was used in combination with AFB1. Furthermore, in AFB1-induced liver
      damage mouse model, VD3 also showed protective effect by reducing HPCs
      population. Together, these preclinical data not only provide a newly identified
      mechanism by which AFB1 affects HPCs but also strengthen the idea of developing
      VD3 as an anticancer agent.

PMID- 30099062
TI  - Clarifying the phylogenetic relationships and taxonomy of Stenonema, Stenacron
      and Maccaffertium, three common eastern North American mayfly genera.
AB  - Stenonema, Stenacron, and Maccaffertium are three closely related genera of
      mayflies (Ephemeroptera:Heptageniidae) commonly found across North America. Due
      to their primarily aquatic life history and sensitivity to aquatic pollutants,
      these mayflies are often used as water quality indicators. However, there is
      little morphological variation within these genera, leading to difficulties in
      identification and rampant taxonomic confusion, limiting their utility as
      bioindicators. In an attempt to resolve the phylogenetic relationships of
      Stenonema, Stenacron, and Maccaffertium, and to clarify their higher-level
      classifications, we sequenced regions of two mitochondrial genes (cytochrome
      oxidase subunit 1 (cox1) and 16S ribosomal RNA (rrnl)) and two nuclear genes
      (Wingless (Wg) and histone H3) from 60 individuals representing most of the
      described species in these genera and included data from representatives of three
      heptageniid genera (Kageronia, Macdunnoa and Pseudiron) proposed in previous
      studies to be closely related to our focal taxa as well as two more distantly
      related heptageniid genera (Epeorus and Heptagenia) to root the phylogenies.
      Maximum likelihood and Bayesian analysis were conducted on single-gene and
      concatenated multi-gene data sets and species tree methods were utilized to
      resolve relationships. These analyses resolved Stenacron as a monophyletic group
      sister to a clade comprising Macdunnoa, Maccaffertium and Stenonema.
      Maccaffertium was found to be paraphyletic, with Stenonema femoratum resolved
      within Maccaffertium as sister to M. mexicanum. Many relationships remained
      unresolved or varied across analyses, making revision of the classification based
      on phylogenetic considerations challenging. To minimize confusion while naming
      clades and acknowledging uncertainty in our phylogenetic conclusions, we redefine
      Stenonema to include Maccaffertium and propose three subgenera-Stenonema,
      Maccaffertium and Lewisa- for key well-supported clades.

PMID- 30099063
TI  - Lineage diversity and reproductive modes of the Daphnia pulex group in Chinese
      lakes and reservoirs.
AB  - Recent studies of the distribution and diversity of freshwater zooplankton have
      indicated that the previously understudied Eastern Palearctic region is an
      important biogeographic hotspot. Here, we explored the lineage diversity and
      reproductive modes of the Daphnia pulex species group across China. Members of
      this group are often keystone species of standing water bodies and are frequently
      used as a model system for ecological, evolutionary and, more recently, genomic
      studies. We found members of the D. pulex group in seven of seventy-six Chinese
      water bodies examined. We analyzed their phylogenetic position using
      mitochondrial markers, and explored the genetic structure of six populations
      using microsatellite markers. Mitochondrial DNA analysis suggested the presence
      of two distinct species complexes in China: the D. pulex complex that has a
      global distribution, and an apparently endemic Eastern Palearctic D. mitsukuri
      complex. Microsatellite analyses of six populations suggested that three of these
      reproduced by cyclical parthenogenesis, as evidenced by high clonal diversity and
      the absence of deviations from the Hardy-Weinberg equilibrium. In contrast, three
      other populations showed remarkably low diversity of multilocus genotypes. This
      suggests an obligate parthenogenetic reproductive mode, which was confirmed in
      one of the populations by comparison of genotypes of Daphnia adults and dormant
      embryos. All presumably obligate parthenogenetic clones were heterozygous at the
      majority of microsatellite loci, suggesting their hybrid origin. This was further
      supported by analyses of a small GTPase nuclear gene (rab4), as two alleles
      within single individuals belonged to different clades. Interestingly, one
      putatively obligate parthenogenetic clone carried three distinct alleles
      suggesting higher ploidy and potential gene flow between the D. pulicaria and D.
      mitsukuri complexes. Our data show that the expansion of the D. pulex complex in
      the Eastern Palearctic was associated with widespread hybridization.

PMID- 30099064
TI  - Aryl hydrocarbon receptor activation by benzo(a)pyrene inhibits proliferation of
      myeloid precursor cells and alters the differentiation state as well as the
      functional phenotype of murine bone marrow-derived macrophages.
AB  - Intensive research during the past decade has highlighted the impact of the
      regulatory function of the aryl hydrocarbon receptor (AhR) in immunity. In this
      study, we focused on the influence of AhR activation on the differentiation of
      murine bone marrow-derived myeloid precursor cells into mature macrophages. Our
      results show that the activation of AhR by subtoxic doses of the AhR ligand
      benzo(a)pyrene (BaP) impaired the proliferation of bone marrow cells (BMCs)
      whereas the proportion of resulting adherent cells was not affected. Flow
      cytometric analysis revealed that the number of mature bone marrow-derived
      macrophages (BMMs) was significantly decreased by AhR activation. However,
      expression of the murine macrophage marker F4/80, the major histocompatibility
      complex class II (MHC-II) and the Fcgamma receptor I (FcgammaRI/CD64) were
      upregulated on BaP-exposed BMMs in an AhR-dependent manner. Analysis of cytokine
      secretion after BMM activation with heat-killed (hk) salmonellae showed that BaP
      exposure resulted in suppressed secretion of interleukin (IL)-1beta, IL-6 and the
      chemokine CXC motif ligand 1 (CXCL1). In contrast, the release of tumor necrosis
      factor (TNF)-alpha and IL-10 was increased following BaP exposure. In addition,
      the production of antimicrobial nitric oxide (NO) was increased AhR-dependently.
      Bacterial stimulation of BaP exposed BMMs also induced the expression of MHC-II
      and CD64, while the expression of F4/80 was dramatically decreased. In summary,
      this study demonstrates for the first time that sustained exposure over 6 days of
      bone marrow-derived myeloid precursors to subtoxic doses of BaP critically
      interferes with differentiation and activation of BMMs. We could convincingly
      show that AhR-induced gene regulation is crucial for homeostasis of pro- and anti
      inflammatory cytokines during macrophage activation.

PMID- 30099066
TI  - Importance of bioavailable calcium in fluoride dentifrices for enamel
      remineralization.
AB  - OBJECTIVES: To compare remineralization of enamel subsurface lesions by fluoride
      dentifrices with added calcium in a double-blind, randomized, cross-over, in situ
      study. METHODS: Human enamel with subsurface lesions were prepared and inserted
      into intra-oral appliances worn by volunteers. A slurry (1 g toothpaste/4 ml H2O)
      was rinsed for 60 s, 4 times per day for 14 days. Seven toothpastes were tested:
      (i) 1450 ppm F (NaF), (ii) 5000 ppm F (NaF), (iii) 1450 ppm F (MFP) with calcium
      sodium phosphosilicate (CSP), (iv) 1450 ppm F (MFP) with CaCO3/Arg, (v) 1150 ppm
      F (SnF2) with amorphous calcium phosphate (ACP), (vi) 1100 ppm F (NaF) with
      casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and (vii) 5000 ppm F
      (NaF) with functionalized tri-calcium phosphate (TCP). Total (acid soluble) and
      bioavailable (water soluble) calcium, inorganic phosphate and fluoride levels of
      the dentifrices were measured using ion chromatography (F/MFP) and
      spectrophotometry (Ca and inorganic phosphate). Enamel lesion mineral content was
      measured using transverse microradiography. Data were statistically analysed
      using a linear mixed model. RESULTS: All calcium and fluoride containing
      toothpastes released > 90% of bioavailable fluoride and were superior to the
      respective fluoride alone toothpastes in remineralization of enamel subsurface
      lesions. The level of remineralization followed the order: CPP-ACP/1l00 ppm F >
      ACP/1150 ppm F = TCP/5000 ppm F > 5000 ppm F = CaCO3/Arg/1450 ppm F = CSP/1450
      ppm F > 1450 ppm F. Bioavailable calcium levels significantly correlated with
      enhanced remineralization of enamel subsurface lesions. CONCLUSIONS: Bioavailable
      calcium in fluoride dentifrices enhanced remineralization of enamel subsurface
      lesions.

PMID- 30099065
TI  - The effects of benzophenone-3 on apoptosis and the expression of sex hormone
      receptors in the frontal cortex and hippocampus of rats.
AB  - Benzophenone-3 (BP-3) is the most commonly used chemical UV filter. This compound
      can easily be absorbed through the skin and the gastrointestinal tract and can
      disturb sex hormone receptor function. BP-3 is lipophilic and should cross the
      blood-brain barrier and it may reduce the survival of neurons, although so far,
      its effects on nerve cells have been studied in only in vitro cultures. The aim
      of the present study was to determine the effects of BP-3 on apoptosis and the
      expression of oestrogen, androgen and arylhydrocarbon receptors (AhR) in the rat
      frontal cortex and hippocampus. This compound was administered dermally to female
      rats during pregnancy and next to their male offspring through 6 and 7 weeks of
      age. BP-3 in the frontal cortex induced the mitochondrial apoptosis pathway by
      increasing the active forms of caspase-3 and caspase-9, inducing the pro
      apoptotic proteins Bax and Bak and increasing the number of cells with apoptotic
      DNA fragmentation. In the hippocampus, an increase in the caspase-9 level and a
      downward trend in the level of anti-apoptotic proteins were observed. In both
      brain regions, the contents of ERbeta in the nuclear fraction and GPR30 in the
      membrane fraction were significantly reduced. BP-3 significantly increased AhR in
      the cytosol of the frontal cortex but had no effect on the content of this
      receptor in the hippocampus. This is the first study showing that exposure to BP
      3 induces the mitochondrial apoptosis pathway in the rat frontal cortex and this
      effect may result from a weakening of the neuroprotective effects of oestrogen
      and/or an intensification of AhR-mediated apoptosis.

PMID- 30099067
TI  - Observed and self-reported assessments of caregivers' feeding styles: Variable-
      and person-centered approaches for examining relationships with children's eating
      behaviors.
AB  - BACKGROUND: Demandingness and responsiveness are dimensions used in general
      parenting as well as the feeding literature to measure parent attitudes and
      behaviors. These dimensions can be treated as continuous variables (variable
      centered) or used to form groups of parents based on scores on each dimension
      (person-centered). Research focusing on these dimensions in the feeding domain
      has relied exclusively on maternal self-reports; observational studies of feeding
      styles have yet to be conducted. OBJECTIVES: The purpose of this study was to
      investigate the effectiveness of variable-centered versus person-centered
      analyses in examining relationships between maternal feeding styles, child eating
      behaviors, and child weight status using both self-reported and observational
      methods for assessing parental feeding style. METHODS: Participants included 137
      low-income Head Start mothers and their preschoolers. Mothers completed the
      Caregiver's Feeding Styles Questionnaire and the Children's Eating Behavior
      Questionnaire. Parent/child interactions were observed during dinner meals at
      home and were coded using a previously developed coding system. RESULTS: Maternal
      demandingness during feeding was negatively associated with child BMI z-scores
      and positively associated with slowness in eating and satiety responsiveness.
      Maternal responsiveness was associated positively with enjoyment of food and
      associated negatively with food fussiness. Significant demandingness by
      responsiveness interactions showed that children of authoritarian mothers showed
      the highest levels of food fussiness and the lowest enjoyment of food. Overall,
      the findings were stronger for the self-report than for the observational
      measures and the variable-centered approach was clearly superior to the person
      centered approach. CONCLUSIONS: The current results indicate that for research
      purposes the variable-centered approach may be the most powerful for examining
      relationships between maternal feeding and child eating. However, for clinical
      purposes, the person-centered approach might be most informative.

PMID- 30099069
TI  - The effect of a mindfulness-based decentering strategy on chocolate craving.
AB  - According to the elaborated-intrusion theory of desire, strategies that load
      visual working memory will reduce cravings. According to the grounded cognition
      theory of desire, cravings will be reduced with mindfulness-based decentering
      strategies that encourage individuals to see their thoughts as thoughts. However,
      decentering strategies also tend to load visual working memory making it
      difficult to test the latter prediction. This study addressed this issue by
      matching visualization across decentering and guided imagery tasks. Male and
      female participants (n = 101) underwent a chocolate craving induction before
      listening to a 4-min audio recording that guided them to (a) decenter from their
      thoughts and feelings, (b) engage in visualization, or (c) let their mind wander.
      Participants reported on chocolate craving before and after the craving induction
      and following the 4-min recording. They also provided retrospective reports of
      craving during the recording, reported on the extent to which they had adhered to
      the audio instructions and briefly indicated what they had been thinking about
      during the recording. Results showed a significant reduction in cravings to
      baseline following the recording across all three conditions (p < .001), but no
      significant differences between conditions or in the retrospective reports of
      craving. There was some evidence to suggest that participants in the mind
      wandering condition had been thinking about alternate goals, which may have
      inhibited thoughts about chocolate and been just as effective at reducing craving
      as the imagery and decentering strategies. Exploratory analyses showed a trend
      toward decentering being more effective than imagery where participants reported
      higher task adherence throughout the 4 min (p = .067). This raises the
      possibility that decentering effects may be improved with better strategy
      adherence, which might be achieved through practice or increased motivation.

PMID- 30099070
TI  - Context-dependent effects of temperature on starvation resistance in Drosophila
      melanogaster: Mechanisms and ecological implications.
AB  - Temperature can modulate the responses of ectotherms to environmental stressors,
      such as food shortage. Temperature-mediated plasticity in starvation resistance
      can arise by changes in the amount of energy stored, the speed of energy
      expenditure, or the threshold energy reserves required for survival. However, few
      studies have investigated how temperature affects these physiological mechanisms
      underlying starvation resistance. In this study, we first examined the
      mechanistic basis of the temperature dependence of starvation resistance in
      Drosophila melanogaster. We then tested whether the effects of temperature on
      starvation resistance would depend on diet and developmental stage in this
      species. We found that exposure to high temperature during starvation
      significantly reduced the capacity of D. melanogaster to resist starvation. This
      warming-induced decrease in starvation resistance was mainly caused by faster
      depletion of body lipids and not by lower threshold lipid content for survival.
      D. melanogaster exposed to higher temperatures during feeding accumulated more
      body lipids and thus became more starvation resistant. Such positive effect of
      high feeding temperature on starvation resistance was pronounced when D.
      melanogaster consumed carbohydrate-rich diets. D. melanogaster raised as larvae
      at low temperature (18  degrees C) had a weaker starvation resistance at adult
      emergence compared to those raised at higher temperatures (23 and 28  degrees C).
      These results demonstrate that the effects of temperature on starvation responses
      are highly context-dependent in D. melanogaster.

PMID- 30099068
TI  - Antecedents of picky eating behaviour in young children.
AB  - BACKGROUND: Picky eating behaviour in young children is a common concern for
      parents. OBJECTIVE: To investigate early life factors which are associated with a
      child becoming a picky eater. DESIGN: Singleton children from the Avon
      Longitudinal Study of Parents and Children were studied prospectively (n = 5758
      6608). Parental-completion questionnaires were used to define 'picky eating'
      status at age 3 years, and child and parental feeding behaviours and practices
      throughout the first 2 years of life. Multinomial logistic regression models with
      3 levels of picky eating (not, somewhat and very picky) as the dependant
      variables tested associations with antecedent variables, from pregnancy, and the
      first and second year of life, separately, then combining all significant
      variables in a final model. RESULTS: Feeding difficulties during complementary
      feeding and late introduction of lumpy foods (after 9 months) were associated
      with increased likelihood of the child being very picky. A strong predictor was
      the child being choosy at 15 months, particularly if the mother was worried about
      this behaviour. Many children (56%) were considered to be choosy at 15 months:
      17% went on to be very picky at 3 years if the mother was not worried, compared
      with 50% if the mother was very worried by the choosiness. The mother providing
      fresh fruit and eating the same meal as the child were protective against later
      'picky eating', while feeding ready-prepared food was predictive. CONCLUSION:
      Advice and support to parents could help to reduce picky eating behaviour.
      Parents should be encouraged to introduce lumpy foods by 9 months, to feed fresh
      foods particularly fruit, and to eat with their children. Parents should be
      reassured that choosiness is normal and to continue to provide a variety of
      foods.

PMID- 30099071
TI  - A Rare Case of Small Bowel Obstruction.

PMID- 30099072
TI  - Re: Regular use of aspirin or non-aspirin nonsteroidal anti-inflammatory drugs is
      not associated with risk of incident pancreatic cancer in two large cohort
      studies.

PMID- 30099073
TI  - Multiple Unusual Ulcerated Skin Lesions in a Crohn's Disease Patient.

PMID- 30099074
TI  - Combined Inactivation of TP53 and MIR34A Promotes Colorectal Cancer Development
      and Progression in Mice Via Increasing Levels of IL6R and PAI1.
AB  - BACKGROUND & AIMS: Combined inactivation of the microRNA 34a gene (MIR34A, by
      methylation) and the TP53 gene (by mutation or deletion) is observed in 50% of
      colorectal tumors that progress to distant metastases. We studied mice with
      intestinal disruption of Mir34a and Tp53 to investigate mechanisms of colorectal
      carcinogenesis and identify strategies to block these processes. METHODS: Mice
      with disruption of Mir34a and/or Tp53 specifically in intestinal epithelial cells
      (IECs) (Mir34aDeltaIEC mice, Tp53DeltaIEC mice, and Mir34aDeltaIEC/Tp53DeltaIEC
      mice) and controls (Mir34aFl/Fl/Tp53Fl/Fl) were given azoxymethane to induce
      colorectal carcinogenesis. Some mice were given intraperitoneal injections of an
      antibody against mouse interleukin 6 receptor (IL6R), or received an inhibitor of
      PAI1 (tiplaxtinin) in their chow. Intestinal tissues were collected and analyzed
      by immunohistochemistry; gene expression profiles were analyzed by RNA
      sequencing. We determined the expression and localization of PAI1 in 61 human
      primary colon cancers and compared them to MIR34A methylation and inactivating
      mutations in TP53. Data on mRNA levels, methylation, and clinical features of 628
      colon and rectal adenocarcinomas were obtained from The Cancer Genome Atlas
      portal. RESULTS: Mir34aDeltaIEC/Tp53DeltaIEC mice developed larger and more
      colorectal tumors, with increased invasion of surrounding tissue and metastasis
      to lymph nodes, than control mice or mice with disruption of either gene alone.
      Cells in tumors from the Mir34aDeltaIEC/Tp53DeltaIEC mice had decreased apoptosis
      and increased proliferation compared to tumor cells from control mice, and
      expressed higher levels of genes, that regulate inflammation (including Il6r and
      Stat3) and epithelial-mesenchymal transition. The gene expression pattern of the
      tumors from Mir34aDeltaIEC/Tp53DeltaIEC mice was similar to that of human
      colorectal tumor consensus molecular subtype 4 (mesenchymal, invasive). We
      identified the Pai1 messenger RNA as a target of Mir34a; levels of PAI1 protein
      were increased in primary colon cancer samples, that displayed methylation of
      MIR34A and mutational inactivation of TP53. Administration of tiplaxtinin or anti
      IL6R antibody to Mir34aDeltaIEC/Tp53DeltaIEC mice decreased proliferation of
      cancer cells, and reduced colorectal tumor invasion and metastasis. CONCLUSIONS:
      In mice, we demonstrated that combined inactivation of Mir34a and Tp53 promotes
      azoxymethane-induced colorectal carcinogenesis and tumor progression and
      metastasis by increasing levels of IL6R and PAI1. Strategies to inhibit these
      processes might be developed to slow progression of colorectal cancer.

PMID- 30099075
TI  - Gastrointestinal Complications and Management of Obesity.

PMID- 30099077
TI  - Multi-modal brain fingerprinting: A manifold approximation based framework.
AB  - This work presents an efficient framework, based on manifold approximation, for
      generating brain fingerprints from multi-modal data. The proposed framework
      represents images as bags of local features which are used to build a subject
      proximity graph. Compact fingerprints are obtained by projecting this graph in a
      low-dimensional manifold using spectral embedding. Experiments using the T1/T2
      weighted MRI, diffusion MRI, and resting-state fMRI data of 945 Human Connectome
      Project subjects demonstrate the benefit of combining multiple modalities, with
      multi-modal fingerprints more discriminative than those generated from individual
      modalities. Results also highlight the link between fingerprint similarity and
      genetic proximity, monozygotic twins having more similar fingerprints than
      dizygotic or non-twin siblings. This link is also reflected in the differences of
      feature correspondences between twin/sibling pairs, occurring in major brain
      structures and across hemispheres. The robustness of the proposed framework to
      factors like image alignment and scan resolution, as well as the reproducibility
      of results on retest scans, suggest the potential of multi-modal brain
      fingerprinting for characterizing individuals in a large cohort analysis.

PMID- 30099079
TI  - Pick your trade-offs wisely: Predator-prey eco-evo dynamics are qualitatively
      different under different trade-offs.
AB  - In recent decades, myriad studies have explored the population dynamics of
      coevolving populations of predator and prey. A variety of choices are made in
      these models: exponential or logistic prey growth in the absence of a predator,
      various forms of predator functional response, and uni- or bi-directional trait
      axes. In addition, some form of trade-offs are assumed in order to prevent run
      away evolution of the prey and predator traits. While there is a considerable
      amount of theory regarding various forms of prey growth rates and predator
      functional responses, only a few studies have explored how different types of
      trade-offs affect predator-prey dynamics. Here, we compared two ditrophic
      coevolution models incorporating different trade-offs via dual effects of the
      prey trait on attack rate and either prey carrying capacity or intrinsic growth
      rate. We employed a standard dynamical systems approach to analyze the
      equilibrium conditions of each model and find conditions for non-equilibrium
      oscillatory coexistence. The exact effect of various parameters on the outcome of
      predator-prey interactions depends on whether the trade-offs affect the intrinsic
      growth rate or carrying capacity. In particular, coexistence is more likely when
      prey growth rate is affected by the evolving trait. In addition, in parameter
      regimes where cycles occur in both models, oscillations typically have larger
      periods and amplitudes when prey growth rate is affected by the evolving trait.

PMID- 30099076
TI  - Comparing fully automated state-of-the-art cerebellum parcellation from magnetic
      resonance images.
AB  - The human cerebellum plays an essential role in motor control, is involved in
      cognitive function (i.e., attention, working memory, and language), and helps to
      regulate emotional responses. Quantitative in-vivo assessment of the cerebellum
      is important in the study of several neurological diseases including cerebellar
      ataxia, autism, and schizophrenia. Different structural subdivisions of the
      cerebellum have been shown to correlate with differing pathologies. To further
      understand these pathologies, it is helpful to automatically parcellate the
      cerebellum at the highest fidelity possible. In this paper, we coordinated with
      colleagues around the world to evaluate automated cerebellum parcellation
      algorithms on two clinical cohorts showing that the cerebellum can be parcellated
      to a high accuracy by newer methods. We characterize these various methods at
      four hierarchical levels: coarse (i.e., whole cerebellum and gross structures),
      lobe, subdivisions of the vermis, and the lobules. Due to the number of labels,
      the hierarchy of labels, the number of algorithms, and the two cohorts, we have
      restricted our analyses to the Dice measure of overlap. Under these conditions,
      machine learning based methods provide a collection of strategies that are
      efficient and deliver parcellations of a high standard across both cohorts,
      surpassing previous work in the area. In conjunction with the rank-sum
      computation, we identified an overall winning method.

PMID- 30099080
TI  - Evolutionary analysis and structural characterization of Aquilaria sinensis
      sesquiterpene synthase in agarwood formation: A computational study.
AB  - Agarwood originating from Aquilaria sinensis contains sesquiterpenoids that have
      tremendous commercial value in the pharmaceutical and fragrance industries.
      Aquilaria sinensis sesquiterpene synthase (AsSTS) is the key enzyme in the
      agarwood biosynthesis pathway, and its activity directly affects the chemical
      composition of agarwood; however, its role in species evolution remains unclear.
      In this study, we performed an evolutionary analysis based on 68 plant
      sesquiterpene synthase (STS) genes and further structural characterization of the
      gene encoding AsSTS to explore its molecular evolution. The phylogenetic tree
      indicated that these STS genes included three subfamilies. Additionally, 23
      positively selected sites were detected, and no influence of recombination was
      found. Furthermore, the protein structure of AsSTS was characterized using
      primary sequence and structural analyses as having a functional active site lid
      domain, a substrate binding site, two post-translational modification sites and
      four conserved motifs. Finally, most virtual mutations of positively selected
      sites could be stabilized against thermal denaturation by a decrease in free
      energy, and three virtual mutations (D403R, G470Q and S538K) were shown to play
      important roles in the function and stability of AsSTS. The molecular
      evolutionary analysis of plant STSs provides essential clues for further
      experimental site-directed mutagenesis and molecular modification of AsSTS.

PMID- 30099081
TI  - PET Radioligands for imaging of the PDE10A in human: current status.
AB  - The development of beta+ emitter tracers labelled with carbon-11 or fluorine-18
      having optimal characteristics of affinity and selectivity for the
      phosphodiesterase 10 A protein has received considerable attention, due to the
      major implication of this enzyme in neurological and psychiatric disorders, such
      as Hungtington's disease, Parkinson's disease and schizophrenia. The ability to
      quantify PDE10 A availability in the human brain in vivo will thus aid
      understanding its role in neurodegenerative and neuropsychiatric pathophysiology
      as well as providing a valuable tool for drug development. This manuscript
      reviews the different compound series assessed to date as PET radioligand for the
      PDE10 A in human and their use to support the development programmes of novel
      drugs or to evaluate PDE10 A alterations in pathologies as Huntington's,
      Parkinson's Diseases and Schizophrenia.

PMID- 30099082
TI  - Functional MRI findings, pharmacological treatment in major depression and
      clinical response.
AB  - Major depressive disorders are common conditions with relatively limited response
      to treatment. In order to improve response to treatment, a better understanding
      of functional neuroanatomy is necessary to improve treatment targets at brain
      level. This work summarises the literature of longitudinal functional magnetic
      resonance imaging studies in major depression to identify brain regions where
      aberrant neural activity normalises after clinical response following treatment
      with pharmacological compounds with known antidepressant properties.
      Hyperactivity in regions such as the amygdala and the ventral components of the
      anterior cingulate cortex were some of the most replicated findings of functional
      MRI studies in major depression and normalisation of aberrant activity one of the
      best predictive biomarkers of treatment response.

PMID- 30099078
TI  - Functional connectivity within the voice perception network and its behavioural
      relevance.
AB  - Recognizing who is speaking is a cognitive ability characterized by considerable
      individual differences, which could relate to the inter-individual variability
      observed in voice-elicited BOLD activity. Since voice perception is sustained by
      a complex brain network involving temporal voice areas (TVAs) and, even if less
      consistently, extra-temporal regions such as frontal cortices, functional
      connectivity (FC) during an fMRI voice localizer (passive listening of voices vs
      non-voices) has been computed within twelve temporal and frontal voice-sensitive
      regions ("voice patches") individually defined for each subject (N = 90) to
      account for inter-individual variability. Results revealed that voice patches
      were positively co-activated during voice listening and that they were
      characterized by different FC pattern depending on the location
      (anterior/posterior) and the hemisphere. Importantly, FC between right frontal
      and temporal voice patches was behaviorally relevant: FC significantly increased
      with voice recognition abilities as measured in a voice recognition test
      performed outside the scanner. Hence, this study highlights the importance of
      frontal regions in voice perception and it supports the idea that looking at FC
      between stimulus-specific and higher-order frontal regions can help understanding
      individual differences in processing social stimuli such as voices.

PMID- 30099083
TI  - Speech analysis for health: Current state-of-the-art and the increasing impact of
      deep learning.
AB  - Due to the complex and intricate nature associated with their production, the
      acoustic-prosodic properties of a speech signal are modulated with a range of
      health related effects. There is an active and growing area of machine learning
      research in this speech and health domain, focusing on developing paradigms to
      objectively extract and measure such effects. Concurrently, deep learning is
      transforming intelligent signal analysis, such that machines are now reaching
      near human capabilities in a range of recognition and analysis tasks. Herein, we
      review current state-of-the-art approaches with speech-based health detection,
      placing a particular focus on the impact of deep learning within this domain.
      Based on this overview, it is evident while that deep learning based solutions be
      become more present in the literature, it has not had the same overall dominating
      effect seen in other related fields. In this regard, we suggest some possible
      research directions aimed at fully leveraging the advantages that deep learning
      can offer speech-based health detection.

PMID- 30099084
TI  - A guide to nucleic acid detection by single-molecule kinetic fingerprinting.
AB  - Conventional methods for detecting small quantities of nucleic acids require
      amplification by the polymerase chain reaction (PCR), which necessitates prior
      purification and introduces copying errors. While amplification-free methods do
      not have these shortcomings, they are generally orders of magnitude less
      sensitive and specific than PCR-based methods. In this review, we provide a
      practical guide to a novel amplification-free method, single-molecule recognition
      through equilibrium Poisson sampling (SiMREPS), that provides both single
      molecule sensitivity and single-base selectivity by monitoring the repetitive
      interactions of fluorescent probes to immobilized targets. We demonstrate how
      this kinetic fingerprinting filters out background arising from the inevitable
      nonspecific binding of probes, yielding virtually zero background signal. As
      practical applications of this digital detection methodology, we present the
      quantification of microRNA miR-16 and the detection of the mutation EGFR L858R
      with an apparent single-base discrimination factor of over 3 million.

PMID- 30099085
TI  - Public acceptability of computer-controlled antibiotic management: An exploration
      of automated dosing and opportunities for implementation.
AB  - A paucity of data describing citizen perceptions of novel technologies, including
      those containing unsupervised computer-controlled systems is currently available.
      We explored citizen perceptions of using a microneedle biosensor and automated
      dose control system at a university public festival. Groups of citizens (from 2-6
      people per group) attended a short demonstration of a microneedle biosensor and
      automated dosing system versus a traditional phlebotomy approach over a two-day
      public festival. Individual groups discussed and reached consensus on a number of
      short questions regarding their perceptions on the acceptability of such
      technology. Over the two days, 100 groups participated (56/100 day 1 and 44/100
      day 2). The majority of individuals reported high acceptability of microneedle
      technology (median Likert score 9/10), but the majority believed that doctors
      should decide what dose of antibiotic is delivered (75/100; 75%). Groups
      concurred with the acceptability of microneedles to reduce blood tests and pain
      associated with them. However, concerns were reported over unsupervised computer
      controlled programmes making decision about antibiotic dosing. This was driven by
      concerns over computer error and the inability of systems to contextualise
      decision making to the human and social context. Future work must consider the
      greater role of citizen engagement in the development of such technologies, to
      ensure their acceptability upon implementation in clinical practice.

PMID- 30099086
TI  - Effects of bisphenol analogs on thyroid endocrine system and possible interaction
      with 17beta-estradiol using GH3 cells.
AB  - This study was conducted using a rat pituitary (GH3) cell line to understand the
      effects of bisphenol analogs (BPs) on the thyroid endocrine system, in the
      presence of 17beta-estradiol (E2). In the first series of experiments, changes in
      cell proliferation were examined after exposure to each of ten BPs, in the
      absence or presence of a median effective concentration (6.4 * 10-10 M) of
      triiodothyronine (T3). All tested BPs significantly increased cell proliferation,
      suggesting thyroid hormone (TH) agonistic effects of BPs. BPs did not potentiate
      the T3-induced cell proliferation at 48 h exposure, while several tested BPs
      including BPA, BPAF, BPB, BPF, BPS, and BPZ elicited a potentiating effect on the
      T3-induced cell proliferation at 96 h exposure. These results indicate that TH
      antagonistic effects of BPs depend on the tested dose and exposure time. In the
      second set of experiments, one of the most potent BPs, i.e., BPAF, was selected,
      and its possible interaction with E2 on the thyroid endocrine system was
      evaluated. Co-exposure of GH3 cells to 10-12 M E2 showed an additive-like effect.
      The extent of increase in cell proliferation was more pronounced with a
      combination of BPAF and E2 than with that of BPA and E2. Significant down
      regulation of Tralpha, Trbeta, and Dio2 genes and up-regulation of the Tshbeta
      gene were observed in GH3 cells following co-exposure to BPAF and E2. Our results
      showed that some BP analogs might influence the thyroid endocrine system, and
      such perturbation appeared to be enhanced in the presence of E2.

PMID- 30099087
TI  - Effect of aqueous dilution on the absorption of the nerve agent VX through skin
      in vitro.
AB  - The in vitro percutaneous penetration of the nerve agent VX through pig skin was
      measured in the absence and presence of water or artificial sweat to determine
      the impact such conditions might have on penetration rates. Experiments were
      performed with Franz-type glass diffusion cells containing dermatomed pig skin as
      a surrogate for human skin. The receptor fluid used was 50% aqueous ethanol. 14C
      labelled VX was applied to the skin surface under infinite or finite dosing
      conditions with regular receptor fluid sampling up to 24 h. Penetration from
      aqueous solutions of VX showed the maximal steady state penetration rate (Jss)
      was from the 50% (v:v) solution (366 +/- 149 MUg.cm-2.h-1), this being ~2.2 fold
      greater than Jss measured for neat VX (169 +/- 89 MUg.cm-2.h-1). Application of
      neat VX to water-wetted skin was also found to result in an increased penetration
      rate, compared to dry skin, shortly after contamination. These studies have shown
      that, in vitro, aqueous solutions of VX in contact with the skin can result in
      increased penetration rates when compared to neat VX applied to dry skin.

PMID- 30099089
TI  - Upstream regulators of apoptosis mediates methionine-induced changes of lipid
      metabolism.
AB  - Although the role of methionine (Met), as precursor for l-carnitine synthesis, in
      the regulation of lipid metabolism has been explored. Met seems to have tissue-
      and species-specific regulatory effect on lipid metabolism, implying that the
      mechanisms in Met regulation of lipid metabolism is complex and may involve the
      upstream regulatory pathway of lipid metabolism. The present study was performed
      to determine the mechanism of apoptosis signaling pathways mediating Met-induced
      changes of hepatic lipid deposition and metabolism in fish, and compare the
      differences of the mechanisms between the fish and mammals. By iTRAQ-based
      quantitative proteome analyses, we found that both dietary Met deficiency and
      excess evoked apoptosis signaling pathways, increased hepatic lipid deposition
      and caused aberrant hepatic lipid metabolism of yellow catfish Pelteobagrus
      fulvidraco. Using primary hepatocytes from P. fulvidraco, inhibition of caspase
      by Z-VAD-FMK blocked the apoptotic signaling pathways with a concomitant reversal
      of Met deficiency- and excess-induced increase of lipid deposition, indicating
      that apoptosis involved the Met-mediated changes of hepatic lipid metabolism.
      Moreover, we explored the roles of three upstream apoptotic signaling pathways
      (PI3K/AKT-TOR pathway, cAMP/PKA/CREB pathway and LKB1/AMPK-FOXO pathway)
      influencing hepatic lipid metabolism of P. fulvidraco. The three upstream
      pathways participated in apoptosis mediating Met-induced changes of lipid
      metabolism in P. fulvidraco. At last, HepG2 cell line was used to compare the
      similarities of mechanisms in apoptosis mediating Met-induced changes of lipid
      metabolism between fish and mammals. Although several slight differences existed,
      apoptosis mediated the Met-induced changes of lipid metabolism between fish and
      mammals. The present study reveals novel apoptosis-relevant signal transduction
      axis which mediates the Met-induced changes of lipid metabolism, which will help
      understand the mechanistic link between apoptosis and lipid metabolism, and
      highlight the importance of the evolutionary conservative apoptosis signaling
      axis in regulating Met-induced changes of hepatic lipid metabolism.

PMID- 30099088
TI  - Establishing a systematic framework to characterise in vitro methods for human
      hepatic metabolic clearance.
AB  - Hepatic metabolic clearance is one of the most important factors driving the
      overall kinetics of chemicals including substances used in various product
      categories such as pesticides, biocides, pharmaceuticals, and cosmetics. A large
      number of in vitro systems from purified isozymes and subcellular organelles to
      hepatocytes in simple cultures and in complex scaffold setups are available for
      measuring hepatic metabolic clearance for different applications. However, there
      is currently no approach for systematically characterising and comparing these in
      vitro methods in terms of their design, applicability and performance. To address
      this, existing knowledge in the field of in vitro human hepatic metabolic
      clearance methods was gathered and analysed in order to establish a framework to
      systematically characterise methods based on a set of relevant components. An
      analogous framework would be also applicable for non-human in vitro systems. The
      components are associated with the biological test systems used (e.g. subcellular
      or cells), the in vitro method (e.g. number of cells, test item solubility),
      related analytical techniques, data interpretation methods (based on substrate
      depletion/metabolite formation), and performance assessments (precision and
      accuracy of clearance measurements). To facilitate the regulatory acceptance of
      this class of methods, it is intended that the framework provide the basis of
      harmonisation work within the OECD.

PMID- 30099090
TI  - Primary mouse brain pericytes isolated from transgenic Alzheimer mice
      spontaneously differentiate into a CD11b+ microglial-like cell type in vitro.
AB  - Alzheimer's disease (AD) is characterized by amyloid-beta plaques, tau pathology
      and vascular impairment including pericyte damage. Pericytes are perivascular
      cells of the blood-brain barrier and can differentiate into different cell types
      in vitro including microglia. The aim of the present study is to explore if
      primary mouse brain pericytes isolated and cultured from transgenic AD
      (APP_SweDI) mice can differentiate into CD11b+ (integrin alpha M) microglia in
      vitro. We show that primary pericytes (passage 5) isolated from wildtype C57BL6
      mice differentiated into CD11b+ microglia (Type B, >90%), when exposed to a
      differentiation factor mix of FGF-2, cAMP and fibronectin. This differentiation
      was time-dependent and seen as a large 80 kDa CD11b fragment (days 1-8) and a
      smaller 50 kDA CD11b fragment (>4 days). These pericytes did not differentiate
      into neurons, astroglia or oligodendroglia. However, pericytes isolated from
      transgenic AD mice differentiated into CD11b+ microglia (Type A, <10%) without
      addition of exogenous differentiation factors, displayed moderate Iba1+
      immunostaining and phagocytic activity, but were still positive for PDGFRbeta. In
      conclusion, we show for the first time that primary mouse pericytes from AD mice
      have the potential to spontanously differentiate in vitro into a CD11b+
      microglial-like (Type A) cell type, but we do not provide evidence that these
      pericytic microglia display a full active microglial cell.

PMID- 30099091
TI  - A highly sensitive and selective high pressure liquid chromatography with tandem
      mass spectrometry (HPLC/MS-MS) method for the direct peptide reactivity assay
      (DPRA).
AB  - While the HPLC/UV (high performance liquid chromatography coupled with ultra
      violet spectrometry)-based DPRA (Direct Peptide Reactivity Assay) identifies
      dermal sensitizers with approximately 80% accuracy, the low selectivity and
      sensitivity of the HPLC/UV-based DPRA poses challenges to accurately identify the
      sensitization potential of certain chemicals. In this study, a high performance
      liquid chromatography coupled with tandem mass spectrometry (HPLC/MS-MS)-based
      DPRA was developed and validated according to the test guideline (OECD TG 442C).
      The final results were compared with the results from the traditional HPLC/UV
      based guideline DPRA. This HPLC/MS-MS-based DPRA demonstrated similar performance
      compared to HPLC/UV-based DPRA using known dermal sensitizers and non-sensitizers
      according to the test guideline (OECD TG 442C). Following the validation, a
      challenge set of chemicals with either overlapping retention time with peptides,
      or higher hydrophobicity or chemicals potentially forming non-covalent
      interactions with peptides were assessed for dermal sensitization potential using
      both methods and the results were compared to existing in vivo data. The HPLC/MS
      MS-based DPRA correctly predicted these chemicals as sensitizers or non
      sensitizers; however, the HPLC/UV-based DPRA resulted in false-positive
      predictions for hydrophobic substances, chemicals with UV peaks overlapping with
      those of the peptide(s), and compounds that non-covalently interact with the
      peptides. These findings demonstrate the broader applicability and better
      sensitivity and selectivity of the LC/MS-MS-based DPRA over the traditional
      HPLC/UV-based guideline DPRA.

PMID- 30099092
TI  - Balancing the risks to individual and society: a systematic review and synthesis
      of qualitative research on antibiotic prescribing behaviour in hospitals.
AB  - BACKGROUND: Antimicrobial resistance is a global health threat, partly driven by
      inappropriate antibiotic prescriptions for acute medical patients in hospitals.
      AIM: To provide a systematic review of qualitative research on antibiotic
      prescribing decisions in hospitals worldwide, including broad-spectrum antibiotic
      use. METHODS: A systematic search of qualitative research on antibiotic
      prescribing for adult hospital patients published between 2007 and 2017 was
      conducted. Drawing on the Health Belief Model, a framework synthesis was
      conducted to assess threat perceptions associated with antimicrobial resistance,
      and perceived benefits and barriers associated with antibiotic stewardship.
      FINDINGS: The risk of antimicrobial resistance was generally perceived to be
      serious, but the abstract and long-term nature of its consequences led physicians
      to doubt personal susceptibility. While prescribers believed in the benefits of
      optimizing prescribing, the direct link between over-prescribing and
      antimicrobial resistance was questioned, and prescribers' behaviour change was
      frequently considered futile when fighting the complex problem of antimicrobial
      resistance. The salience of individual patient risks was a key barrier to more
      conservative prescribing. Physicians perceived broad-spectrum antibiotics to be
      effective and low risk; prescribing broad-spectrum antibiotics involved low
      cognitive demand and enabled physicians to manage patient expectations.
      Antibiotic prescribing decisions in low-income countries were shaped by a context
      of heightened uncertainty and risk due to poor microbiology and infection control
      services. CONCLUSIONS: When tackling antimicrobial resistance, the tensions
      between immediate individual risks and long-term collective risks need to be
      taken into account. Efforts to reduce diagnostic uncertainty and to change risk
      perceptions will be critical in shifting practice.

PMID- 30099093
TI  - EZH1 is an antipsychotic-sensitive epigenetic modulator of social and
      motivational behavior that is dysregulated in schizophrenia.
AB  - BACKGROUND: With the capacity to modulate gene networks in an environmentally
      sensitive manner, the role of epigenetic systems in mental disorders has come
      under intense investigation. Dysregulation of epigenetic effectors, including
      microRNAs and histone-modifying enzymes, may better explain the role of
      environmental risk factors and the observed heritability rate that cannot be
      fully attributed to known genetic risk alleles. Here, we aimed to identify novel
      epigenetic targets of the schizophrenia-associated microRNA 132 (miR-132).
      METHODS: Histone modifications were quantified by immunodetection in response to
      viral-mediated overexpression of miR-132 while a luminescent reporter system was
      used to validate targets of miR-132 in vitro. Genome-wide profiling, quantitative
      PCR and NanoSting were used to quantify gene expression in post-mortem human
      brains, neuronal cultures and prefrontal cortex (PFC) of mice chronically exposed
      to antipsychotics. Following viral-mediated depletion of Enhancer of Zeste 1
      (EZH1) in the murine PFC, behaviors including sociability and motivation were
      assessed using a 3-chambered apparatus and forced-swim test, respectively.
      RESULTS: Overexpression of miR-132 decreased global histone 3 lysine 27 tri
      methylation (H3K27me3), a repressive epigenetic mark. Moreover, the polycomb
      associated H3K27 methyltransferase, EZH1, is regulated by miR-132 and upregulated
      in the PFC of schizophrenics. Unlike its homolog EZH2, expression of EZH1 in the
      murine PFC decreased following chronic exposure to antipsychotics. Viral-mediated
      depletion of EZH1 in the mouse PFC attenuated sociability, enhanced motivational
      behaviors, and affected gene expression pathways related to neurotransmission and
      behavioral phenotypes. CONCLUSIONS: EZH1 is dysregulated in schizophrenia,
      sensitive to antipsychotic medications, and a brain-enriched miR-132 target that
      controls neurobehavioral phenotypes.

PMID- 30099094
TI  - Targeting neurodegeneration to prevent post-traumatic epilepsy.
AB  - In the quest for developing new therapeutic targets for post-traumatic epilepsies
      (PTE), identifying mechanisms relevant to development and progression of disease
      is critical. A growing body of literature suggests involvement of
      neurodegenerative mechanisms in the pathophysiology of acquired epilepsies,
      including following traumatic brain injury (TBI). In this review, we discuss the
      potential of some of these mechanisms to be targets for the development of a
      therapy against PTE.

PMID- 30099095
TI  - Traditional medicinal plants of Agri Province, Turkey.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: This study serves as the first investigation of
      the knowledge of traditional medicinal plants used in Agri Province. The
      mountainous and strongly fragmented area, diversity of local flora, limited
      access to modern medicines because of the people's seminomadic lifestyle, and
      harsh climatic conditions have prompted the locals to benefit from natural
      resources, principally plants. AIM OF THE STUDY: Although the use of medicinal
      plant is common in the area, documentation and inventory analysis are not
      available on the plant taxa used in traditional medicine in Agri Province. This
      study focused on the answer of the following question: What are the most
      medicinally valuable plant taxa in the province? Therefore, this study aimed to
      (i) document medicinal plant taxa used in Agri Province; (ii) determine the
      endemic plant species and their risk categories; (iii) determine the most widely
      used plant taxa for specific ailments to further contribute to drug discovery;
      (iv) determine the local names, plant part(s) used, preparation, and utilization
      methods of these local plant medicines to assist with pharmaceutical studies; and
      (v) reveal the origin(s) of traditional medicinal knowledge of Agri Province.
      MATERIALS AND METHODS: Ethnopharmacological field studies were conducted between
      2014 and 2016 in 638 locations within Agri Province. Plant samples used in folk
      medicine were determined through face-to-face interviews with 120 local healers.
      Traditional medicinal plant samples were collected from wild areas with the help
      of the local healers and transported to Van Pharmaceutical Herbarium (Van,
      Turkey) for botanical identification. The statistical analyses of data were
      conducted using the informant consensus factor (ICF) method. RESULTS: In this
      study, 118 medicinal taxa belonging to 35 families of plants were determined to
      be used in Agri Province. Ninety-three different local names were recorded, which
      mainly described the plant's morphological characteristics. Data analysis (ICF)
      revealed that the traditional medicinal plants used in Agri Province might offer
      promising information for new pharmaceuticals. CONCLUSIONS: The local population
      in the study area has a preserved and comprehensive knowledge of traditional
      medicine because of its limited access to modern medicine, seminomadic lifestyle,
      isolated geographical position, traditional taste habits, climatic conditions,
      diversity of local flora, and mountainous and rugged geography. The medicinal
      plants presented in this study might provide valuable leads for the
      identification of bioactive compounds for pharmaceutical use and represent a vast
      and underutilized resource for the development of newer and more efficient
      pharmacological treatments.

PMID- 30099096
TI  - Effects of dietary nitrate supplementation, from beetroot juice, on blood
      pressure in hypertensive pregnant women: A randomised, double-blind, placebo
      controlled feasibility trial.
AB  - Chronic hypertension in pregnancy is associated with significant adverse
      pregnancy outcomes, increasing the risk of pre-eclampsia, fetal growth
      restriction and preterm birth. Dietary nitrate, abundant in green leafy
      vegetables and beetroot, is reduced in vivo to nitrite and subsequently nitric
      oxide, and has been demonstrated to lower blood pressure, improve vascular
      compliance and enhance blood flow in non-pregnant humans and animals. The primary
      aims of this study were to determine the acceptability and efficacy of dietary
      nitrate supplementation, in the form of beetroot juice, to lower blood pressure
      in hypertensive pregnant women. In this double-blind, placebo-controlled
      feasibility trial, 40 pregnant women received either daily nitrate
      supplementation (70 mL beetroot juice, n = 20) or placebo (70 mL nitrate-depleted
      beetroot juice, n = 20) for 8 days. Blood pressure, cardiovascular function and
      uteroplacental blood flow was assessed at baseline and following acute (3 h) and
      prolonged (8 days) supplementation. Plasma and salivary samples were collected
      for analysis of nitrate and nitrite concentrations and acceptability of this
      dietary intervention was assessed based on questionnaire feedback. Dietary
      nitrate significantly increased plasma and salivary nitrate/nitrite
      concentrations compared with placebo juice (p < 0.001), with marked variation
      between women. Compared with placebo, there was no overall reduction in blood
      pressure in the nitrate-treated group; however there was a highly significant
      correlation between changes in plasma nitrite concentrations and changes in
      diastolic blood pressure in the nitrate-treated arm only (r = -0.6481; p =
      0.0042). Beetroot juice supplementation was an acceptable dietary intervention to
      97% of women. This trial confirms acceptability and potential efficacy of dietary
      nitrate supplementation in pregnant women. Conversion of nitrate to nitrite
      critically involves oral bacterial nitrate reductase activities. We speculate
      that differences in efficacy of nitrate supplementation relate to differences in
      the oral microbiome, which will be investigated in future studies.

PMID- 30099098
TI  - The Microbiome in Cirrhosis and Its Complications.
AB  - The microbiome in cirrhosis is affected by multiple processes occurring at the
      level of the gut and systemically. This dysbiosis, or unfavorable microbiota
      profile, is present at several body sites and is associated with higher systemic
      inflammation, bacterial infections and poor outcomes. This increased morbidity in
      cirrhosis stems from an immune paralysis state that is partly related to the
      constant stimulation of the immune system by this dysbiosis. Dysbiosis as a
      dynamic event worsens with decompensation such as with hepatic encephalopathy,
      infections or acute-on-chronic liver failure (ACLF). These microbial patterns
      could be applied as diagnostic and prognostic measures in cirrhosis in the
      outpatient and inpatient setting. Current therapies for cirrhosis have differing
      impacts on gut microbial composition and functionality. Dietary modifications and
      the oral cavity have emerged as newer targetable factors to modulate the
      microbiome, which could affect inflammation and, potentially improve outcomes.
      Additionally, fecal microbial transplant is being increasingly studied to provide
      compositional and functional modulation of the microbiome. Ultimately, a
      combination of targeted therapies may be needed to provide an optimal gut milieu
      to improve outcomes in cirrhosis.

PMID- 30099099
TI  - A Rare Case of Asymptomatic Primary Gastric Localized Amyloidosis.

PMID- 30099097
TI  - Signaling interplay between primary cilia and nitric oxide: A mini review.
AB  - New discoveries into the functional role of primary cilia are on the rise. In
      little more than 20 years, research has shown the once vestigial organelle is a
      signaling powerhouse involved in a vast number of essential cellular processes.
      In the same decade that interest in primary cilia was burgeoning, nitric oxide
      won molecule of the year and a Nobel prize for its role as a near ubiquitous
      signaling molecule. Although primary cilia and nitric oxide are both involved in
      signaling, a direct relationship has not been investigated; however, after a
      quick review of the literature, parallels between their functions can be drawn.
      This review aims to suggest a possible interplay between primary cilia and nitric
      oxide signaling especially in the areas of vascular tissue homeostasis and
      cellular proliferation.

PMID- 30099100
TI  - Neuroendocrine Tumor Presenting as a Large Gastric Ulcer.

PMID- 30099101
TI  - Porphyria Cutanea Tarda Improvement With Elbasvir/Grazoprevir in End-Stage Renal
      Disease.

PMID- 30099102
TI  - Gastric Hamartomatous Inverted Polyp Causing Ball Valve Syndrome.

PMID- 30099103
TI  - Intramucosal Metastasis of Gastric Cancer to the Duodenum.

PMID- 30099105
TI  - Quantification of Antibody to Hepatitis B Core Antigen to Predict Outcomes of
      Patients With HBV Infection.

PMID- 30099104
TI  - Safety and Acceptability of a Nonendoscopic Esophageal Sampling Device -
      Cytosponge: A Systematic Review of Multicenter Data.
AB  - BACKGROUND & AIMS: Diagnosis and surveillance of Barrett's esophagus (BE) and
      eosinophilic esophagitis (EoE) have become emerging public health issues.
      Cytosponge(r) is a novel, minimally invasive esophageal cell collection device.
      We aimed to assess the data on safety and acceptability of this device. METHODS:
      We performed a patient-level review of 5 prospective trials assessing
      Cytosponge(r) performance in patients with reflux disease, BE and EoE in primary
      and secondary care. Acceptability of Cytosponge(r) and subsequent endoscopy were
      recorded with visual analogue scale (VAS), wherein 0 and 10 denoted lowest and
      highest acceptability. Median VAS scores were compared using a Mann-Whitney test.
      The number of attempts, failures in swallowing the device and occurrence of
      adverse events were analyzed. Risk factors for failure in swallowing were
      analyzed using a multivariate regression model. RESULTS: In total 2,672
      Cytosponge(r) procedures were performed in 2,418 individuals between 2008 and
      2017. There were two adverse events related to the device: a minor pharyngeal
      bleed and one case of detachment (<1:2,000). The median acceptability score for
      the Cytosponge(r) was 6.0 (IQR 5.0-8.0), which was higher than endoscopy without
      sedation (median 5.0, IQR 3.0-7.0; P < .001) and lower than endoscopy with
      sedation (median 8.0, IQR 5.0-9.0; P < .001). Nearly all patients (91.1%)
      successfully swallowed the Cytosponge(r) and most (90.1%) were achieved with the
      first swallow attempt. Failure to swallow the device was more likely to occur in
      secondary care (OR= 5.13, 95% CI 1.48-17.79, P < .01). CONCLUSIONS: The
      Cytosponge(r) test is a safe procedure with good acceptability ratings in a
      variety of health care settings.

PMID- 30099106
TI  - When to Resume Direct Oral Anticoagulants Following Gastrointestinal Bleeding.

PMID- 30099107
TI  - ???.

PMID- 30099108
TI  - Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease.
AB  - DESCRIPTION: The purpose of this clinical practice update review is to describe
      key principles in the diagnosis and management of functional gastrointestinal
      (GI) symptoms in patients with inflammatory bowel disease (IBD). METHODS: The
      evidence and best practices summarized in this manuscript are based on relevant
      scientific publications, systematic reviews, and expert opinion where applicable.
      Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory
      activity should be followed in IBD patients with persistent GI symptoms
      (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional
      imaging). Best practice advice 2: In those patients with indeterminate fecal
      calprotectin levels and mild symptoms, clinicians may consider serial
      calprotectin monitoring to facilitate anticipatory management. Best practice
      advice 3: Anatomic abnormalities or structural complications should be considered
      in patients with obstructive symptoms including abdominal distention, pain,
      nausea and vomiting, obstipation or constipation. Best practice advice 4:
      Alternative pathophysiologic mechanisms should be considered and evaluated (small
      intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance,
      chronic pancreatitis) based on predominant symptom patterns. Best practice advice
      5: A low FODMAP diet may be offered for management of functional GI symptoms in
      IBD with careful attention to nutritional adequacy. Best practice advice 6:
      Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness
      therapy) should be considered in IBD patients with functional symptoms. Best
      practice advice 7: Osmotic and stimulant laxative should be offered to IBD
      patients with chronic constipation. Best practice advice 8: Hypomotility agents
      or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD. Best
      practice advice 9: Antispasmodics, neuropathic-directed agents, and anti
      depressants should be used for functional pain in IBD while use of opiates should
      be avoided. Best practice advice 10: Probiotics may be considered for treatment
      of functional symptoms in IBD. Best practice advice 11: Pelvic floor therapy
      should be offered to IBD patients with evidence of an underlying defecatory
      disorder. Best practice advice 12: Until further evidence is available, fecal
      microbiota transplant should not be offered for treatment of functional GI
      symptoms in IBD. Best practice advice 13: Physical exercise should be encourage
      in IBD patients with functional GI symptoms. Best practice advice 14: Until
      further evidence is available, complementary and alternative therapies should not
      be routinely offered for functional symptoms in IBD.

PMID- 30099109
TI  - Erroneous Use of Endoscopic Biopsy Data in Crohn's Disease.

PMID- 30099110
TI  - Patient, Procedure, and Endoscopist Risk Factors for Perforation, Bleeding, and
      Splenic Injury After Colonoscopies.
AB  - BACKGROUND & AIMS: We investigated perforations, bleeding, and splenic injuries
      after screening or diagnostic colonoscopies to identify patient-, procedure-,
      endoscopist-, and facility-associated risk factors. METHODS: We analyzed data
      from the SNIIRAM-PMSI national claims databases in France. A total of 4,088,799
      patients, 30 years or older, undergoing a first screening or diagnostic
      colonoscopy from 2010 through 2015 were identified. Rates of severe adverse
      events (SAEs) were estimated using stringent and broad definitions. Risk factors
      associated with perforations and major bleeding were estimated using multilevel
      logistic regression models, adjusted for patient, colonoscopy, and endoscopist
      characteristics. RESULTS: Perforation rates ranged from 3.5 (stringent
      definition) to 7.3 (broad definition) per 10,000 procedures, bleeding rates
      ranged from 6.5 to 23.1 per 10,000 procedures, and splenic injury rates ranged
      from 0.20 to 0.34 per 10,000 procedures. Rates of 30-day mortality were 13.2 per
      1000 bleeds, 29.2 per 1000 perforations, and 36.1 per 1000 splenic injuries
      (stringent definitions). Patient characteristics associated with SAEs were
      increasing age (especially for perforation), cancer, and cardiovascular
      comorbidities. Procedure characteristics associated with SAEs included
      polypectomy-especially of polyps larger than 1 cm with an increased risk of
      perforation (odds ratio, 4.1; 95% CI, 3.4-5.0) and bleeding (odds ratio, 13.3;
      95% CI, 11.7-15.1). Less-experienced endoscopists and endoscopists who performed
      a smaller number of colonoscopies were independently associated with a risk of
      SAEs. CONCLUSION: In an analysis of national claims databases in France, we found
      SAEs related to screening and diagnostic colonoscopies to be more frequent in
      older patients, in patients with comorbidities, and with less-experienced
      endoscopists. Patients at risk of SAE should be identified and colonoscopies
      should be performed or supervised by experienced endoscopists.

PMID- 30099112
TI  - Herpes Esophagitis That Resembles Candidiasis.

PMID- 30099111
TI  - Sex-Based Differences in the Association Between Nonalcoholic Fatty Liver Disease
      and Mortality.

PMID- 30099113
TI  - Oral Diclofenac Potassium Versus Hyoscine-N-Butyl Bromide in Reducing Pain
      Perception during Office Hysteroscopy: A Randomized Double-blind Placebo
      controlled Trial.
AB  - STUDY OBJECTIVE: To compare the efficacy of oral diclofenac potassium versus
      hyoscine-N-butyl bromide (HBB) in reducing pain perception in patients undergoing
      diagnostic office hysteroscopy (OH). DESIGN: A randomized double-blind placebo
      controlled trial (Canadian Task Force classification I). SETTING: A university
      hospital. INTERVENTIONS: One-hundred twenty-nine patients were divided randomly
      into 3 groups (n = 43 in each group); group 1 received 50 mg diclofenac
      potassium, group 2 received 20 mg HBB, and group 3 received placebo tablets. All
      tablets were taken orally 1 hour before OH. The primary outcome was the
      participant's self-rated pain perception using the 10-point visual analog scale
      during the procedure. The secondary outcomes included the visual analog scale
      score 30 minutes after OH, ease of OH assessment using a 10-cm scale, duration of
      OH, and adverse effects of the study medications. MEASUREMENTS AND MAIN RESULTS:
      Both the diclofenac and HBB groups showed significant pain score reduction
      compared with the placebo group (p = .001). The mean pain score in the diclofenac
      group was significantly lower than the HBB group (2.12 +/- 1.03 vs 3.02 +/- 1.55,
      respectively; p = .002). The pain scores in the diclofenac and HBB groups
      immediately after OH were significantly lower than the placebo group (p = .001),
      and the mean pain score in the diclofenac group was significantly lower than the
      HBB group (1.23 +/- 0.57 vs 1.56 +/- 0.73, respectively; p = .024). The ease of
      procedure score was significantly lower in the diclofenac and HBB groups than the
      placebo group (p = .003 and p = .005, respectively). The mean duration of the
      procedure was significantly less in the diclofenac group (p = .01). Fourteen
      women (32.6%) in the HBB group experienced dizziness and 2 women (4.6%) had
      nausea, whereas only 4 women (9.3%) in the diclofenac group had dizziness and 2
      women (4.6%) had vomiting. CONCLUSION: Oral diclofenac potassium administration 1
      hour before diagnostic OH reduces the procedure pain with subsequent easier and
      shorter OH duration. Oral HBB is less effective than diclofenac potassium with
      more adverse effects.

PMID- 30099114
TI  - Performance of the Michigan Hand Outcomes Questionnaire in hand osteoarthritis.
AB  - OBJECTIVE: To investigate the performance of the Michigan Hand Outcomes
      Questionnaire (MHQ) in hand osteoarthritis (OA) by evaluating truth,
      discrimination and feasibility. DESIGN: Symptomatic hand OA patients from the
      Hand Osteoarthritis in Secondary Care (HOSTAS) cohort completed questionnaires
      (demographics, MHQ, Australian/Canadian Hand Osteoarthritis Index [AUSCAN],
      Functional Index for Hand Osteoarthritis [FIHOA] and visual analogue scale [VAS]
      pain) at baseline (n = 383), 1- and 2-year follow-up (n = 312, n = 293). Anchor
      questions at follow-up assessed whether pain/function levels were (un)acceptable
      and had changed compared to baseline. Correlations between MHQ and other
      pain/function questionnaires were calculated. Validity of unique MHQ domains
      (work performance, aesthetics, satisfaction), discrimination across disease
      stages, and responsiveness were assessed by categorizing patients by external
      anchors (employment, joint deformities, erosions, and anchor questions). Between
      group differences were assessed with linear regression, probability plots and
      comparison of medians. RESULTS: MHQ pain and function subscales correlated
      moderately-to-good with other instruments (rs 0.63-0.81). Work performance scores
      were worse in patients with reduced working capacity than in employed patients.
      Aesthetics scores were worse in patients with more deformities. Patients with
      unacceptable complaints had worse satisfaction scores. All pain/function
      instruments discriminated between patients with acceptable vs unacceptable
      pain/function, while only MHQ activities of daily living (ADL), FIHOA, and MHQ
      aesthetics could discriminate between erosive and non-erosive disease. MHQ and
      AUSCAN were most responsive. CONCLUSIONS: MHQ has several unique aspects and
      advantages justifying its use in hand OA, including the unique assessment of work
      performance, aesthetics, and satisfaction. However, MHQ, AUSCAN and FIHOA appear
      to measure different aspects of pain and function.

PMID- 30099116
TI  - Does experimental cortisol elevation mediate risk-taking and antipredator
      behaviour in a wild teleost fish?
AB  - The hypothalamic-pituitary-interrenal (HPI) axis is centrally implicated in
      stressor mitigation in teleost fishes. Sustained HPI axis activation can be
      detrimental to the physiological functioning of an organism and can result in
      fitness-related trade-offs. Predator-induced mortality is known to be higher in
      stressed fish than in unstressed conspecifics, suggesting a role for the HPI axis
      in mediating fish behaviour. However, the underlying specific mechanism(s) for
      this phenomenon is(are) unknown. The purpose of the current study was to address
      how the HPI axis influences risk-taking, and antipredator behaviours in a wild
      teleost, the pumpkinseed sunfish (Lepomis gibbosus). Here, individual juvenile
      pumpkinseed were implanted either with cocoa butter as a sham control or with a
      biologically-relevant concentration of cortisol. Forty-eight hours post
      implantation, fish were assessed for behavioural metrics associated with boldness
      and risk taking in three sequential behavioural tests: (i) a predation-risk test,
      (ii) an exploration tendency test, and (iii) a shoaling tendency test, with test
      order randomized among different trials. Cortisol treatment had no influence on
      antipredator, exploratory, or shoaling behaviours. However, post-attack swimming
      duration (in predation-risk test) and exploratory activity (in Z-maze exploration
      test) were significantly affected by body mass. Collectively, our results
      indicate that cortisol may not have a role in mediating sociability, boldness,
      and risk-taking behaviours in pumpkinseed sunfish, at least under the current
      laboratory conditions. However, cortisol may nonetheless play a role in mediating
      predator-prey interactions in fishes in more natural environmental settings that
      were not considered here.

PMID- 30099115
TI  - Contribution of central and peripheral risk factors to prevalence, incidence and
      progression of knee pain: a community-based cohort study.
AB  - AIM: To explore risk factors that may influence knee pain (KP) through central or
      peripheral mechanisms. METHODS: A questionnaire-based prospective community
      cohort study with KP defined as pain in or around a knee on most days for at
      least a month. Baseline prevalence, and one year incidence and progression (KP
      worsening) were examined. Central (e.g., Pain Catastrophizing Scale (PCS)) and
      peripheral (e.g., significant injury) risk factors were examined. Adjusted odds
      ratio (OR) and 95% confidence interval (CI) were calculated using logistic
      regression. Proportional risk contribution (PRC) was estimated using receiver
      operator-characteristic (ROC) analysis. RESULTS: Of 9506 baseline participants,
      4288 (45%) had KP (men 1826; women, 2462). KP incidence was 12% (men 11%, women
      13%), and KP progression 19% (men 16%, women 21%) at one year. While both central
      and peripheral factors contributed to prevalence, central factors contributed
      more to progression, and peripheral factors more to incidence of KP. For example,
      although PCS (OR 2.06, 95% CI 1.88-2.25) and injury (5.62, 4.92-6.42) associated
      with KP prevalence, PCS associated with progression (2.27, 1.83-2.83) but not
      incidence (1.14, 0.86-1.52), whereas injury more strongly associated with
      incidence (69.27, 24.15-198.7) than progression (2.52, 1.48-4.30). The PRC of
      central and peripheral factors were 19% and 23% for prevalence, 14% and 29% for
      incidence, and 29% and 5% for progression, respectively. CONCLUSIONS: Both
      central and peripheral risk factors influence KP but relative contributions may
      differ in terms of development (mainly peripheral) and progression (mainly
      central). Further study of such relative contributions may inform primary and
      secondary prevention strategies.

PMID- 30099117
TI  - Target-cell-specific Short-term Plasticity Reduces the Excitatory Drive onto CA1
      Interneurons Relative to Pyramidal Cells During Physiologically-derived Spike
      Trains.
AB  - Short-term plasticity enables synaptic strength to be dynamically regulated by
      input timing. Excitatory synapses arising from the same axon can have profoundly
      different presynaptic forms of short-term plasticity onto inhibitory and
      excitatory neurons. We previously showed that Schaffer collateral synapses onto
      most hippocampal CA1 stratum radiatum interneurons have less paired-pulse
      facilitation than synapses onto CA1 pyramidal cells, but little difference in
      steady-state short-term depression. However, less is known about how synapses
      onto interneurons respond to temporally complex patterns that occur in vivo. Here
      we compared Schaffer collateral synapses onto stratum radiatum interneurons and
      pyramidal cells in acute hippocampal slices in response to physiologically
      derived spike trains. We find that synapses onto interneurons have less short
      term facilitation than synapses onto pyramidal cells, and a subset expresses only
      short-term depression. Mathematical modeling predicts this target cell-specific
      short-term plasticity occurs through differences in initial release probability.
      All three groups have more short-term facilitation during physiologically-derived
      train stimulation than during constant-frequency stimulation at the same
      frequency, indicating that variability in stimulus timing is important. These
      target-cell specific differences in short-term plasticity reduce the strength of
      excitatory input onto interneurons relative to pyramidal cells, and of depression
      interneurons relative to facilitation interneurons, during high frequency
      portions of the train. This occurs to a similar extent at 25  degrees C and at 33
      degrees C, and is even greater at physiological extracellular calcium. Target
      cell specific differences in short-term plasticity enable synapses to have
      different temporal filtering characteristics, which may help to dynamically
      regulate the balance of inhibition and excitation in CA1.

PMID- 30099118
TI  - Primary Neural Degeneration in the Human Cochlea: Evidence for Hidden Hearing
      Loss in the Aging Ear.
AB  - The noise-induced and age-related loss of synaptic connections between auditory
      nerve fibers and cochlear hair cells is well-established from histopathology in
      several mammalian species; however, its prevalence in humans, as inferred from
      electrophysiological measures, remains controversial. Here we look for cochlear
      neuropathy in a temporal-bone study of "normal-aging" humans, using autopsy
      material from 20 subjects aged 0-89 yrs, with no history of otologic disease.
      Cochleas were immunostained to allow accurate quantification of surviving hair
      cells in the organ Corti and peripheral axons of auditory-nerve fibers. Mean loss
      of outer hair cells was 30-40% throughout the audiometric frequency range (0.25
      8.0 kHz) in subjects over 60 yrs, with even greater losses at both apical (low
      frequency) and basal (high-frequency) ends. In contrast, mean inner hair cell
      loss across audiometric frequencies was rarely >15%, at any age. Neural loss
      greatly exceeded inner hair cell loss, with 7/11 subjects over 60 yrs showing
      >60% loss of peripheral axons re the youngest subjects, and with the age-related
      slope of axonal loss outstripping the age-related loss of inner hair cells by
      almost 3:1. The results suggest that a large number of auditory neurons in the
      aging ear are disconnected from their hair cell targets. This primary neural
      degeneration would not affect the audiogram, but likely contributes to age
      related hearing impairment, especially in noisy environments. Thus, therapies
      designed to regrow peripheral axons could provide clinically meaningful
      improvement in the aged ear.

PMID- 30099119
TI  - Assessment of the 11-year nationwide trend of out-of-hospital cardiac arrest
      cases among elderly patients in Japan (2005-2015).
AB  - OBJECTIVE: Japan has one of the most rapidly aging societies worldwide. This
      study aimed to assess the long-term nationwide trend of out-of-hospital cardiac
      arrest (OHCA) cases among elderly patients in Japan. METHODS: This prospective,
      nationwide observational study in Japan included elderly patients aged >=65 years
      who experienced OHCA from January 1, 2005 to December 31, 2015. The patients were
      classified into three groups: young-old, aged 65-74 years; old-old, aged 75-84
      years; and oldest-old, aged >=85 years. The primary outcome of this study was one
      month survival with a favorable neurological outcome, which was defined as a
      cerebral performance category scale score of 1 or 2. RESULTS: A total of 877,009
      patients were included in our analysis. The number of elderly patients with OHCA
      increased from 65,968 in 2005 to 87,339 in 2015, and each age category showed a
      significantly increasing trend (p value <0.001 for each trend). The proportions
      of favorable neurological outcomes also increased from 1.2% in 2005 to 2.8% in
      2015 in the young-old group; from 0.6% in 2005 to 1.1% in 2015 in the old-old
      group; and from 0.2% in 2005 to 0.5% in 2014 in the oldest-old group.
      Furthermore, this improving trend was notable for those with a shockable first
      documented rhythm. CONCLUSIONS: Based on this long-term nationwide observational
      study in Japan, the number of elderly patients with OHCA increased annually, and
      a significant improvement in the patients' neurological outcomes was noted
      regardless of age category, particularly among those with an initially shockable
      rhythm.

PMID- 30099120
TI  - The cost of care for cardiac arrest.

PMID- 30099121
TI  - Spatiotemporal AED optimization is generalizable.
AB  - AIMS: Mathematical optimization of automated external defibrillator (AED)
      placements has the potential to improve out-of-hospital cardiac arrest (OHCA)
      coverage and reverse the negative effects of limited AED accessibility. However,
      the generalizability of optimization approaches has not yet been investigated.
      Our goal is to examine the performance and generalizability of a spatiotemporal
      AED placement optimization methodology, initially developed for Toronto, Canada,
      to the new study setting of Copenhagen, Denmark. METHODS: We identified all
      public OHCAs (1994-2016) and all registered AEDs (2016) in Copenhagen, Denmark.
      We calculated the coverage loss associated with limited temporal accessibility of
      registered AEDs, and used a spatiotemporal optimization model to quantify the
      potential coverage gain of optimized AED deployment. Coverage gain of
      spatiotemporal deployment over a spatial-only solution was quantified through 10
      fold cross-validation. Statistical testing was performed using chi2 and McNemar's
      tests. RESULTS: We found 2149 public OHCAs and 1573 registered AED locations.
      Coverage loss was found to be 24.4% (1104 OHCAs covered under assumed 24/7
      coverage, and 835 OHCAs under actual coverage). The coverage gain from using the
      spatiotemporal model over a spatial-only approach was 15.3%. Temporal and
      geographical trends in coverage gain were similar to Toronto. CONCLUSIONS:
      Without modification, a previously developed spatiotemporal AED optimization
      approach was applied to Copenhagen, resulting in similar OHCA coverage findings
      as Toronto, despite large geographic and cultural differences between the two
      cities. In addition to reinforcing the importance of temporal accessibility of
      AEDs, these similarities demonstrate the generalizability of optimization
      approaches to improve AED placement and accessibility.

PMID- 30099122
TI  - Yeast red pigment modifies cloned human alpha-synuclein pathogenesis in Parkinson
      disease models in Saccharomyces cerevisiae and Drosophila melanogaster.
AB  - Recently, we identified the yeast red pigment (RP), a polymer of 1-(5'
      Phosphoribosyl)-5-aminoimidazole, as a novel potential anti-amyloid agent for the
      therapy of neurodegenerative diseases. The purpose of this study was to further
      validate RP for treatment of Parkinson's disease (PD) and to clarify molecular
      mechanisms involved in the reduction of amyloid cytotoxicity. We investigated RP
      effects in vivo using Saccharomyces cerevisiae and Drosophila melanogaster PD
      models. Western blot analysis revealed reduction in the levels of insoluble alpha
      synuclein in both models, while soluble alpha-synuclein decreased only in
      Drosophila. In both models RP significantly reduced alpha-synuclein cytotoxicity,
      as was revealed by immunohistochemistry in Drosophila (p < 0.001, n = 27 flies
      per genotype/assay) and by flow cytometry in yeast (p < 0.05). Data obtained from
      the yeast PD model suggests that RP antitoxic effects are associated with a drop
      in ROS accumulation, and slower cellular transition from the early to late
      apoptotic stage. Using Drosophila brain tissue sections, we have demonstrated
      that RP helps to compensate for an alpha-synuclein-mediated reduction in the
      number of dopaminergic neurons and leads to better performance in animal climbing
      tests (p < 0.001, n = 120-150 flies per genotype/assay). Taken together, these
      results demonstrate the potential of RP for the treatment of PD, at least in
      model systems.

PMID- 30099123
TI  - Selection of protein conformations for structure-based polypharmacology studies.
AB  - Several drugs exert their therapeutic effect through the modulation of multiple
      targets. Structure-based approaches hold great promise for identifying compounds
      with the desired polypharmacological profiles. These methods use knowledge of the
      protein binding sites to identify stereoelectronically complementary ligands. The
      selection of the most suitable protein conformations to be used in the design
      process is vital, especially for multitarget drug design in which the same ligand
      has to be accommodated in multiple binding pockets. Herein, we focus on currently
      available techniques for the selection of the most suitable protein conformations
      for multitarget drug design, compare the potential advantages and limitations of
      each method, and comment on how their combination could help in polypharmacology
      drug design.

PMID- 30099124
TI  - New leads for drug repurposing against malaria.
AB  - Malaria is threatening a resurgence because of drug resistance against frontline
      artemisinin-based combination therapies (ACTs). This necessitates the development
      of alternate routes for malaria treatment. Here, we present a refined focus on US
      Food and Drug Administration (FDA)-approved over-the-counter (OTC) drugs that
      could be repurposed. We analyzed growth inhibition data for Plasmodium falciparum
      and Plasmodium berghei in the context of 189 and 37 drugs (total of 226),
      respectively. Of these, our analyses revealed 18 currently used drugs that would
      be suitable for further development as potential antimalarials. Eight identified
      drugs share enzymatic targets between the human host and the malaria parasite,
      providing a platform for mechanistic and drug selectivity studies that could
      provide optimized leads as next-generation antimalarials.

PMID- 30099125
TI  - Aging impairs protective host defenses against Clostridioides (Clostridium)
      difficile infection in mice by suppressing neutrophil and IL-22 mediated
      immunity.
AB  - BACKGROUND: Morbidity and mortality associated with Clostridioides (formerly
      Clostridium) difficile infection (CDI) rises progressively with advanced age
      (>=65 years) due in part to perturbations of the gut microbiota and immune
      dysfunction. Epidemiological data of community-acquired CDI suggests increased
      susceptibility may begin earlier during middle-age (45-64 years) but the
      causation remains unknown. METHODS: Middle-aged (12-14 months) and young (2-4
      months) adult mice were infected with C. difficile, and disease severity, gut
      microbiome and innate immune response were compared. Cytokine reconstitution
      studies were performed in infected middle-aged mice. RESULTS: Infection of middle
      aged mice with C. difficile led to greater disease compared to young controls,
      which was associated with increases in C. difficile burden and toxin titers, and
      elevated bacterial translocation. With the exception of an expansion of C.
      difficile in middle-aged mice, microbiome analysis revealed no age-related
      differences. In contrast, middle-aged mice displayed a significant defect in
      neutrophil recruitment to the colon, with diminished levels of innate immune
      cytokines IL-6, IL-23 and IL-22. Importantly, recombinant IL-22 administration
      during CDI reduced morbidity and prevented death in middle-aged mice. CONCLUSION:
      Increased susceptibility to C. difficile occurs in middle-aged mice modeling the
      community-acquired CDI demographics and is driven by an impaired innate immune
      response.

PMID- 30099126
TI  - Could Nonenhanced Computer Tomography Suffice as the Imaging Study of Choice for
      the Screening of Asymptomatic Microscopic Hematuria?
AB  - OBJECTIVE: To compare the diagnostic accuracy of the noncontrast and contrast
      enhanced phases of computed tomographic urography for detection of upper urinary
      tract findings in adults undergoing initial evaluation of newly diagnosed
      asymptomatic microscopic hematuria to determine if less-intensive noncontrast
      imaging has the potential to become a suitable imaging alternative in the work-up
      of this common condition. MATERIALS AND METHODS: Retrospective review from 2010
      2015 for adults who underwent computed tomographic urography for initial
      evaluation of asymptomatic microscopic hematuria. Three nonblinded physicians
      independently categorized the upper urinary tract findings described in the
      computed tomography reports into one of three groups: normal, benign, or
      suspicious for malignancy. The noncontrast images of a randomized portion of the
      studies categorized as normal and all studies categorized as suspicious and
      benign were submitted to two blinded radiologists who independently classified
      each study into one of the aforementioned categories. RESULTS: The noncontrast
      images for 475 subjects were blindly reviewed. When compared to the computed
      tomographic urography reports, the negative predictive values of noncontrast
      images were 97.25% and 94.92% for radiologist 1 and radiologist 2, respectively,
      with an associated specificity of 88.6% and 97.95%. Of the 5 true upper tract
      malignancies, both blinded radiologists correctly identified 4 of the 5.
      CONCLUSION: Contrast imaging added little diagnostic value when compared with
      noncontrast imaging for most subjects undergoing initial evaluation for
      asymptomatic microscopic hematuria. Less-intensive imaging with nonenhanced
      computed tomography could reduce the nontrivial risks associated with multiphasic
      contrast imaging but further work is necessary to identify risk-stratifying
      criteria.

PMID- 30099127
TI  - The Effect of Adjunct Mechanical Traction on Penile Length in Men Undergoing
      Primary Treatment for Peyronie's Disease: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: To accurately characterize the effect of penile traction therapy (PTT)
      on stretched penile length (SPL) after primary treatment for men with PD.
      MATERIALS AND METHODS: A systematic search was performed for studies that
      evaluated the correction of PD using penile traction as secondary treatment
      published through January 2018. Studies were included if (1) a singular primary
      treatment of PD (injection or surgical treatment) was performed for all included
      men, (2) if there was a control group with no adjunct traction, and (3) if
      patients were required to wear the traction device for greater than 2 h/d.
      Estimates were pooled using random-effects meta-analysis. RESULTS: Data were
      obtained from 4 studies involving 348 men with an average age of 55.7 +/- 2.0
      years. Men who used PTT after primary intervention had SPLs 1.02 cm greater [95%
      CI: 0.64 to 1.40; I2=0%] when compared with men who did not use traction after
      primary intervention (p = 0.009). When performing subgroup analysis by primary
      therapy, no difference was seen in men undergoing penile traction after surgical
      correction when compared with men undergoing penile traction after injection
      therapy (1.01 vs 1.29 cm, p = 0.84). CONCLUSION: PTT may be a promising technique
      to reduce length loss in men undergoing PD treatment. Future work should be done
      to determine the ideal timing and subpopulations who would benefit from PTT.

PMID- 30099128
TI  - The Relationship Between Nocturnal Enuresis and Spina Bifida Occulta: A
      Prospective Controlled Trial.
AB  - OBJECTIVE: To compare the frequency of spina bifida occulta (SBO) detected in
      patients with nocturnal enuresis (NE) and to investigate its clinical
      significance. METHODS: Patients aged 6 to 15 years who were admitted to the
      urology clinic with NE were included in this prospective study. The control group
      consisted of patients who were admitted with a complaint of abdominal or lateral
      pain. The patients who had lower urinary tract symptoms (LUTS) were classified as
      nonmonosymptomatic NE (NMNE). Those with monosymptomatic NE were treated with
      desmopressine. In patients with NMNE, treatment with oxybutynin was added if an
      overactive bladder or uninhibited contraction was detected by urodynamics.
      RESULTS: A total of 184 NE and 180 control patients were included in the study.
      SBO was detected in 71 (19.5%) patients and LUTS in 100 (27.4%). When the groups
      with and without NE were compared, the number of patients with SBO (26% vs 17%, P
      = .044) and those with LUTS (36% vs 17.5%, P < .001) were significantly higher in
      the NE group. The overall rate of dryness (67.4% vs 83.6%, P = .024) and response
      to LUTS treatment (65% vs 97%, P < .01) were significantly lower in those with
      SBO than in those without SBO. CONCLUSION: SBO is more common in NE patients than
      in non-NE patients. Response to NE treatment is lower in SBO patients with severe
      LUTS; for this population, advanced treatment options may be considered earlier.

PMID- 30099129
TI  - Comparative Effectiveness of Prostate Cancer Treatment Options: Limitations of
      Retrospective Analysis of Cancer Registry Data.
AB  - PURPOSE: Retrospective analyses of cancer registry and institutional data have
      consistently found better survival after radical prostatectomy versus radiation
      therapy, which contrasts with findings from a randomized trial. This is likely
      because of the inability of retrospective studies to fully account for
      comorbidity differences across treatment groups because of the lack of detailed
      data in the registries. We use a unique population-based data set with detailed
      data regarding comorbidities and functional limitations to assess whether this
      can provide valid comparisons of survival across prostate cancer treatment
      groups. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results
      (SEER)-Medicare Health Outcomes Survey (MHOS) data set results from a linkage
      between the SEER database and the MHOS database, which includes detailed
      information regarding patient-reported comorbidity and functional limitations. We
      analyzed 3102 patients with prostate cancer in SEER-MHOS and used latent class
      analysis to identify the healthiest group with minimal comorbidity burden and
      functional limitations. Among the healthiest group, we examined overall survival
      across treatments using the Kaplan-Meier method. RESULTS: Three distinct health
      groups were identified using latent class analysis; the healthiest group
      comprised 57% of the cohort and had a 10-year overall survival of 67%. Other
      health groups had higher rates of comorbidities or functional limitations. Among
      the healthiest group, 10-year overall survival differed across treatment groups:
      no local treatment (55%), external beam radiation therapy (69%), brachytherapy
      (76%), and radical prostatectomy (85%). Survival curves for the 3 treated groups
      separated at 4 years of follow-up. CONCLUSIONS: Despite the detailed health
      status information available in SEER-MHOS, our retrospective analysis could not
      fully account for patient selection biases across prostate cancer treatment
      groups. These findings highlight an important limitation of retrospective studies
      using population-based data sets and serve as a reminder to interpret results
      with caution.

PMID- 30099130
TI  - Patterns of Failure following Postoperative Radiation Therapy Based on "Tumor Bed
      with Margin" for Stage II-IV Type C Thymic Epithelial Tumor.
AB  - PURPOSE: To report failure pattern in Masaoka-Koga stage II-IV type C thymic
      epithelial tumor (TET) following postoperative radiation therapy (PORT) and to
      evaluate suitability of PORT target volume confined to "tumor bed only with
      margin". METHODS AND MATERIALS: Retrospective review of 53 patients with stage II
      IV type C TET was done. The clinical outcomes, failure pattern in relation to
      PORT target volume, and prognostic factors were analyzed. RESULTS: During the
      median follow-up of 69 months, 14 deaths and 25 recurrences were observed. The 5
      year rates of overall survival (OS), disease-specific survival (DSS), and freedom
      from-recurrence (FFR) were 81.0%, 91.5% and 49.7%, respectively. Failure pattern
      in relation to PORT target volume were in-field failure in two patients (3.8%),
      marginal in two (3.8%), and out-of-field in 23 (43.4%), respectively. The most
      common failure sites were the pleura in 12 patients, followed by lung parenchyme
      in eight, respectively. Relapse involving the regional lymph node was observed in
      six patients, among whom four had synchronous distant failure and only two had
      isolated ipsilateral supraclavicular LN failure. CONCLUSIONS: Policy of PORT
      target volume confined to tumor bed only seems reasonable in treating stage II-IV
      type C TET patients. Development of more effective systemic therapy regimen would
      be warranted.

PMID- 30099132
TI  - Cardiovascular Preventive Care and Coordination Of Care In Prostate Cancer
      Survivors: A Multi-Institutional Prospective Study.
AB  - BACKGROUND: Prostate cancer survivors who receive androgen deprivation therapy
      (ADT) are at increased risk of cardiovascular disease. They require coordinated
      care between cancer specialist and primary care physicians (PCPs) to monitor for
      cancer control and manage cardiovascular risk factors. METHODS: We prospectively
      enrolled 103 men receiving ADT with radiotherapy from 7 institutions to assess
      cardiovascular risk factors and survivorship care. Medical records, fasting labs,
      and patient-reported outcomes using a validated instrument were assessed at
      baseline (pre-treatment) and 1 year post-RT. RESULTS: Cardiovascular disease
      (39%) and risk factors (diabetes 22%, hypertension 63%, hyperlipidemia 31%) were
      prevalent at baseline. During the first year after RT completion, 63% received
      cardiovascular monitoring concordant with American Heart Association guidelines.
      Fasting labs at 1 year showed 24% with inadequately controlled blood sugar, and
      22% elevated cholesterol. Patient perceptions about care coordination were
      relatively low. At 1 year, 57% reported that their PCP "always know about the
      care I receive at other places," 67% reported that their cancer physician
      "communicated with other providers I see," and 65% reported the cancer physician
      "knows the results of my visits with other doctors." CONCLUSIONS: Prostate cancer
      patients who receive ADT and RT are a vulnerable population with prevalent
      baseline cardiovascular disease and risk factors, and suboptimal survivorship
      care specifically related to coordinated care and cardiovascular monitoring.
      Clinical trials examining ways to improve the care and outcomes of these
      survivors are needed.

PMID- 30099131
TI  - Phase 1 study of spinal cord constraint relaxation with single session spine
      stereotactic radiosurgery in the primary management of patients with inoperable,
      previously unirradiated metastatic epidural spinal cord compression.
AB  - In this Phase 1 prospective clinical trial, spinal cord dose constraint
      relaxation up to 16 Gy was not associated with any myelopathy events and may be
      considered in high risk inoperable patients with epidural disease, or metastatic
      epidural spinal cord compression to optimize local control.

PMID- 30099133
TI  - Probiotics and the immunological response to infant vaccinations; a double-blind
      randomized controlled trial.
AB  - OBJECTIVES: To examine the effect of a combination of probiotics on the antibody
      response to pneumococcal and pertussis vaccination in healthy Danish children,
      aged 8-14 months, at the time of starting day care. Moreover, the cytokine
      response to lipopolysaccharide of whole blood was assessed. METHODS: A total of
      290 children were randomly allocated to receive a combination of Bifidobacterium
      animalis ssp. lactis and Lactobacillus rhamnosus GG daily for a 6-month
      intervention period, and blood samples were drawn at the start and end of the
      study. Specific antibody response towards Streptococcus pneumoniae serotypes and
      Bordetella pertussis toxin, as well as endotoxin-induced interleukin-6 (IL-6) and
      interferon-gamma (IFN-gamma) production in blood were analysed by Luminex and
      ELISA. RESULTS: There was no significant difference between the average
      individual changes from baseline to end of study in antibody concentrations for
      S. pneumoniae for both the probiotics (340.4% +/- 11.2%) and the placebo group
      (382.9% +/- 10.4%) (p 0.525), nor for B. pertussis toxin in the two groups
      (probiotics 190.1% +/- 12.6% versus placebo 238.8% +/- 1.1%, p 0.340). The
      average individual change in IL-6 concentration was significantly lower in the
      probiotics versus the placebo group (2.9% +/- 10.3% versus 33.7% +/- 9.0%, p
      0.024), whereas there was no difference in IFN-gamma concentration (0.0% +/- 0.2%
      versus -0.2% +/- 0.1%, p 0.279). CONCLUSIONS: The probiotic intervention did not
      affect the antibody response against S. pneumoniae and B. pertussis toxin in
      healthy Danish children.

PMID- 30099134
TI  - Disseminated Volvariella volvacea infections in patients with haematological
      malignancies: a case series.

PMID- 30099135
TI  - Prevalence of Kingella kingae oropharyngeal carriage and predominance of type a
      and type b polysaccharide capsules among French young children.

PMID- 30099136
TI  - High acquisition rate of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae among French military personnel on mission abroad, without
      evidence of inter-individual transmission.
AB  - OBJECTIVES: Acquisition of extended-spectrum beta-lactamase-producing
      Enterobacteriaceae (ESBL-E) by Europeans travelling individually in high
      endemicity countries is common. However, how the different ESBL-E strains
      circulate in groups of travellers has not been studied. We investigated ESBL-E
      transmission within several groups of French military personnel serving overseas
      for 4-6 months. METHODS: We conducted a prospective study among French military
      personnel assigned to Afghanistan, French Guiana or Cote d'Ivoire for 4-6 months.
      Faecal samples provided by volunteers before leaving and after returning were
      screened for ESBL-E isolates. ESBL Escherichia coli from each military group was
      characterized by repetitive element palindromic polymerase chain reaction (rep
      PCR) fingerprinting followed, in the Afghanistan group, by whole-genome
      sequencing (WGS) if similarity was >=97%. RESULTS: Among the 189 volunteers whose
      samples were negative before departure, 72 (38%) were positive after return. The
      highest acquisition rates were observed in the Afghanistan (29/33, 88%) and Cote
      d'Ivoire (39/80, 49%) groups. Acquisition rates on return from French Guiana were
      much lower (4/76, 5%). WGS of the 20 strains from the Afghanistan group that
      clustered by rep-PCR identified differences in sequence type, serotype,
      resistance genes and plasmid replicons. Moreover, single-nucleotide polymorphism
      (SNP) differences across acquired strains from a given cluster ranged from 30 to
      3641, suggesting absence of direct transmission. CONCLUSIONS: ESBL-E. coli
      acquisition was common among military personnel posted overseas. Many strains
      clustered by rep-PCR but differed by WGS and SNP analysis, suggesting acquisition
      from common external sources rather than direct person-to-person transmission.

PMID- 30099137
TI  - Diet as a risk factor for antimicrobial resistance in community-acquired urinary
      tract infections in a middle-aged and elderly population: a case-control study.
AB  - OBJECTIVES: There is an ongoing debate as to what extent antimicrobial resistance
      (AMR) can be transmitted from animals to humans via the consumption of animal
      products. Because epidemiological data on the role of diet in AMR in humans are
      lacking, we investigated this association between diet and AMR for different
      antimicrobial drugs in Escherichia coli (E. coli) in urinary tract infections
      (UTIs). METHODS: Susceptibility of E. coli in urinary cultures and information on
      diet (with food frequency questionnaires) were obtained from participants of the
      Rotterdam study, a population-based prospective cohort study. The association
      between intake of several food groups (meat, seafood, eggs, dairy products,
      crops) and resistance of E. coli to several antimicrobial drugs (amoxicillin,
      amoxicillin-clavulanic acid, trimethoprim, sulfamethoxazole-trimethoprim, first
      generation cephalosporins, cefotaxime, nitrofurantoin, norfloxacin) was studied.
      RESULTS: Urinary cultures with E. coli were obtained from 612 individuals, of
      whom 481 (78.6%) were women. Resistance rates varied from 246/611 (40.3%) for
      amoxicillin and 167/612 (27.3%) for trimethoprim to only 29/612 (4.7%) for
      nitrofurantoin and 16/462 (3.5%) for cefotaxime. A higher intake of chicken was
      associated with cefotaxime resistance (OR 2.18; 95% CI 1.05-4.51 per tertile
      increase); a higher intake of pork was associated with norfloxacin resistance (OR
      1.42; 95% CI 1.04-1.95 per quartile increase). In contrast, a higher intake of
      cheese was associated with lower AMR to amoxicillin (OR 0.84; 95% CI 0.72-0.99
      per quartile increase) and amoxicillin-clavulanic acid (OR 0.67; 95% CI 0.53-0.86
      per quartile increase). CONCLUSIONS: These findings support the hypothesis that
      diet may play a role in the AMR of E. coli in UTIs.

PMID- 30099138
TI  - Effect of polymerizable quaternary ammonium monomer MEIM-x's alkyl chain length
      and content on bone cement's antibacterial activity and physicochemical
      properties.
AB  - Quaternary ammonium monomers with N-alkyl chain length varied from 6 to 18,
      namely MEIM-x(x = 6-18), were incorporated into acrylic bone cements to prepare
      antibacterial bone cements. With the increasing of MEIM-x's alkyl chain length,
      the MEIM-x monomers' minimum inhibitory concentrations (MIC) decreased to 8
      MUg/mL and 2 MUg/mL (MEIM-14, for E. coli and S. aureus, respectively) at first
      and then increased. The 50% hemolytic concentrations (HC50) decreased
      monotonously with the increasing of alkyl chain length. The bone cements
      contained 2% and 5% of long-chain MEIM-x (x >= 10) showed significant
      antibacterial activity against E. coli and S. aureus, while the bone cements
      contained short-chain MEIM-x(x < 10) showed a weaker activity. Overall, adding 2%
      of MEIM-x had acceptable influences on the bone cements' properties in terms of
      doughing time, setting time, peak temperature, solubility, fluid uptake,
      compressive strength, flexural strength, flexural modulus, hemolysis and
      cytotoxicity, but adding 5% of MEIM-x impaired the bone cements' mechanical
      properties and hemolysis significantly.

PMID- 30099139
TI  - Molecular characterization and function analysis of three RIG-I-like receptor
      signaling pathway genes (MDA5, LGP2 and MAVS) in Oreochromis niloticus.
AB  - The recognition of microbial pathogens, which is mediated by pattern recognition
      receptors (PRRs), is critical to the initiation of innate immune responses. In
      the present study, we isolated the full-length cDNA and genomic DNA sequences of
      the MDA5, LGP2 and MAVS genes in Nile tilapia, termed OnMDA5, OnLGP2 and OnMAVS.
      The OnMDA5 gene encodes 974 amino acids and contains two caspase-associated
      recruitment domains (CARDs), a DExDc domain (DExD/H box-containing domain), a
      HELICc (helicase superfamily C-terminal) domain and a C-terminal regulatory
      domain (RD). The OnLGP2 gene encodes 679 amino acids and contains a DExDc, a
      HELICc and an RD. The OnMAVS gene encodes 556 amino acids and contains a CARD, a
      proline-rich domain, a transmembrane helix domain and a putative TRAF2-binding
      motif (269PVQDT273). Phylogenetic analyses showed that all three genes from Nile
      tilapia were clustered together with their counterparts from other teleost
      fishes. Real-time PCR analyses showed that all three genes were constitutively
      expressed in all examined tissues in Nile tilapia. OnMDA5 presented the highest
      expression level in the blood and the lowest expression level in the liver, while
      OnMAVS presented the highest expression level in the kidney. The highest
      expression level of OnLGP2 was detected in the liver. An examination of the
      expression patterns of these RIG-I-like receptors (RLRs) during embryonic
      development showed that the highest expression levels of OnMDA5 occurred at 2
      days postfertilization (dpf), and the expression significantly decreased from 3
      to 8 dpf. The expression levels of OnLGP2 significantly increased from 4 to 8
      dpf. The expression levels of OnMAVS mRNA were stable from 2 to 8 dpf. Upon
      stimulation by intraperitoneal injection of Streptococcus agalactiae, the
      expression levels of OnMDA5 were first downregulated and then upregulated in the
      blood, gill and spleen. In the intestine and kidney, the expression of OnMDA5 was
      first upregulated, then downregulated, and then upregulated again. The expression
      of OnLGP2 was upregulated in the kidney and intestine, and the expression of
      OnMAVS was upregulated in the spleen. Overexpression of OnMAVS increased NF
      kappaB activation in 293 T cells (p < 0.05), and after cotransfection with
      OnMDA5, the OnMAVS-dependent NF-kappaB activation was slightly increased (p >
      0.05), after cotransfection with OnLGP2, the OnMAVS-dependent NF-kappaB
      activation was significantly decreased (p < 0.05). These findings suggest that,
      although the deduced protein structure of OnMDA5 is evolutionarily conserved with
      the structures of other RLR members, its signal transduction function is markedly
      different. The results also suggest that OnLGP2 has a negative regulatory effect
      on the OnMAVS gene. OnMDA5 and OnMAVS were uniformly distributed throughout the
      cytoplasm in 293 T cells, whereas OnLGP2 was distributed throughout the cytoplasm
      and nucleus. These results are helpful for clarifying the innate immune response
      against bacterial infection in Nile tilapia.

PMID- 30099140
TI  - Morphological and functional characterization of clam Ruditapes philippinarum
      haemocytes.
AB  - Clam Ruditapes philippinarum is one of the most important commercial aquaculture
      species in China. The haemocytes play vital roles in internal defense of the
      calm. In this investigation, classification and immune functions of R.
      philippinarum haemocytes were identified. The haemocyte density was (8.28 +/-
      1.42) * 106/mL and two major haemocyte types basophilic hyalinocytes and
      eosinophilic granulocytes were recognized based on the presence or absence of
      granules and staining affinities of their cytoplasm. Granulocytes were the most
      common cell type (73.08 +/- 3.23%). The hyalinocytes and granulocytes could be
      divided into eight subtypes respectively according to N/C ratio as well as the
      nucleus shape and number by light microscope. Fourteen types of granules were
      identified and the multivesicular body and R-body were first found in bivalve,
      moreover, transmission electron microscope observation was consistent with the
      results from light microscope. Also eight different external forms of haemocytes
      could be identified by scanning electron microscope. Both granulocytes and
      hyalinocytes showed the abilities of phagocytosis and reactive oxygen species
      (ROS) production which were higher in granulocytes than that in hyalinocytes. The
      phagocytic rate of the total haemocytes and the granulocytes was about 45.06% and
      40.74% respectively. The ROS production of the total haemocytes and granulocytes
      was 58.7% and 51.19% respectively. Although the hyalinocytes showed less ability
      in phagocytosis and ROS production, they played important roles in agglutination.
      This investigation provided a fundamental knowledge for future study of the
      immune function of haemocytes in clam R. philippinarum.

PMID- 30099141
TI  - Functional characterization of grass carp runt-related transcription factor 3:
      Involvement in TGF-beta1-mediated c-Myc transcription in fish cells.
AB  - In mammals, both runt-related transcription factor 3 (RUNX3) and c-Myc are the
      downstream effectors of transforming growth factor-beta1 (TGF-beta1) signaling to
      mediate various cellular responses. However, information of their interaction
      especially in fish is lacking. In the present study, grass carp (Ctenopharyngodon
      idella) runx3 (gcrunx3) cDNA was cloned and identified. Interestingly, opposing
      effects of recombinant grass carp TGF-beta1 (rgcTGF-beta1) on c-myc and runx3
      mRNA expression were observed in grass carp periphery blood lymphocytes (PBLs).
      Parallelly, Runx3 protein levels were enhanced by rgcTGF-beta1 in the cells.
      These findings prompted us to examine whether Runx3 can mediate the inhibition of
      TGF-beta1 on c-myc expression in fish cells. In line with this, overexpression of
      grass carp Runx3 and Runx3 DN (a dominant-negative form of Runx3) in grass carp
      kidney cell line (CIK) cells decreased and increased c-myc transcript levels,
      respectively. Particularly, the regulation of Runx3 and Runx3 DN on c-myc mRNA
      expression was direct since they were presented in the nucleus without any
      stimulation. In addition, rgcTGF-beta1 alone suppressed c-myc mRNA expression in
      CIK cells as in PBLs. Moreover, this inhibitory effect was also observed when
      grass carp Runx3 and Runx3 DN were overexpressed. These results strengthened the
      role of TGF-beta1 signaling in controlling c-myc transcription. Taken together,
      TGF-beta1-mediated c-myc expression was affected at least in part by Runx3,
      thereby firstly exploring the functional role of Runx3 in TGF-beta1 down
      regulation on c-myc mRNA expression in fish.

PMID- 30099142
TI  - A mannose receptor is involved in the anti-Vibrio defense of red swamp crayfish.
AB  - Mannose receptor (MR), a member of pattern-recognition receptors (PRRs), is the
      first MR family member to be discovered that plays a critical role in immunity.
      The function of MRs has been reported in mammals and teleosts while none in
      invertebrates. In the present study, we identified a MR-like gene (designated as
      PcMR) from red swamp crayfish, Procambarus clarkii. The PcMR cDNA is 6848 bp long
      with a 6288 bp open reading frame that encodes a polypeptide with 2095 amino acid
      residues. PcMR transcripts were mainly detected in hepatopancreas and hemocytes,
      and upregulated by Vibrio anguillarum challenge. The PcMR protein contained 14 C
      type lectin domains (CTLDs) and they were divided into four fragments (CTLD 1-3,
      CTLD 4-6, CTLD 7-10, CTLD 11-14). The four recombinant proteins encoded by the
      four fragments were all expressed and purified. Microorganism-binding and sugar
      binding assay showed that CTLD 1-3, CTLD 4-6, CTLD 7-10, CTLD 11-14 could bind to
      a variety of bacteria, as well as glycoconjugates on the bacterial surface.
      Moreover, they agglutinated bacteria in a calcium-dependent manner. Bacteria
      clearance experiment manifested that the mixed proteins facilitated the clearance
      of injected bacteria in crayfish. PcMR silencing by siRNA interference impaired
      the bacterial clearance ability. These results suggest PcMR is involved in the
      antibacterial defense of crayfish, and this study will help us better understand
      the functions of invertebrate MRs.

PMID- 30099143
TI  - Dietary yeast hydrolysate and brewer's yeast supplementation could enhance growth
      performance, innate immunity capacity and ammonia nitrogen stress resistance
      ability of Pacific white shrimp (Litopenaeus vannamei).
AB  - An 8-week feeding trial was conducted to evaluate the effects of dietary yeast
      hydrolysate and brewer's yeast supplementation on growth, immune-related genes
      expression and ammonia nitrogen stress resistance of Pacific white shrimp
      (Litopenaeus vannamei). Three isonitrogenous and isolipidic practical diets were
      formulated to contain 0% (control diet), 1% yeast hydrolysate and 1% brewer's
      yeast, respectively. 360 juvenile L. vannamei with an initial weight (0.88 +/-
      0.01 g) was randomly divided into 3 treatments in four replicates (30 shrimp per
      replicate). The results indicated that shrimp fed the diet containing 1% yeast
      hydrolysate had a significantly higher weight gain (WG), and specific growth rate
      (SGR) than that fed the control diet, and the lowest feed conversion ratio (FCR)
      was occurred in the 1% yeast hydrolysate supplementation group. Proximate
      composition in whole body and muscle among all treatments was not significantly
      influenced by the dietary yeast hydrolysate or brewer's yeast supplementation.
      The challenge test with ammonia nitrogen showed that lower cumulative survival
      was observed in those fed the control diet, and the highest cumulative survival
      was occurred at shrimp fed the 1% yeast hydrolysate supplementation. Shrimp fed
      the control diet had higher inflammation-related genes expression levels of tnf
      alpha and il-1beta in the intestine than those fed the diets supplemented with 1%
      yeast hydrolysate or 1% brewer's yeast, however, there was no significant
      difference in expression level of alp in intestine among all treatments. The
      relative expression levels of mTOR signal pathway genes (eif4ebp, eif4e1a, eif4e2
      and p70s6k) were significantly up-regulated in the shrimp fed the diets
      supplemented with 1% yeast hydrolysate, and the lowest gene expression levels of
      eif4ebp, eif4e1a, eif4e2 and p70s6k in the intestine were occurred at the control
      diet. The highest expression levels of the immune-related genes (dorsal, relish,
      and proPO) in the intestine were observed at shrimp fed the 1% yeast hydrolysate
      supplementation, and the lowest expression levels of these genes were occurred at
      shrimp fed the control diet, however, there was no significant difference in gene
      expression of lysozyme among all treatments. The expression levels of
      penaeidin3a, crustin, proPO, and IMD in the hepatopancreas were significantly
      influenced by the dietary yeast hydrolysate, brewer's yeast or no yeast product
      supplementation, shrimp fed the 1% yeast hydrolysate supplementation had higher
      expression levels of these genes than those fed the control diet. The present
      study indicated that dietary 1% yeast hydrolysate or brewer's yeast
      supplementation could improve growth performance, enhance innate immunity, and
      strengthen resistance of ammonia nitrogen stress, and dietary 1% yeast
      hydrolysate supplementation provides better immunostimulatory effects than
      brewer's yeast of L. vannamei.

PMID- 30099144
TI  - Ovarian function following immunocontraceptive vaccination of mares using native
      porcine and recombinant zona pellucida vaccines formulated with a non-Freund's
      adjuvant and anti-GnRH vaccines.
AB  - An important determinant in the selection of any contraceptive agent is the
      impact on ovarian function, both in the short and longer term. In this study,
      ovarian activity was monitored in mares immunised with one of the following
      vaccine formulations; native porcine zona pellucida (pZP), recombinant zona
      pellucida proteins ZP3 and ZP4 (reZP), pZP and reZP combined or a commercially
      available anti-GnRH vaccine. The ZP antigens were prepared in an adjuvant
      formulation consisting of 6% polymeric adjuvant (MontanideTM PetGel A, Seppic,
      France) and 500 MUg polyinosinic-polycytidylic acid - TLR3-agonist (Poly(I:C) HMW
      VacciGradeTM, Invivogen, USA). A vehicle-only control group was administered the
      adjuvant formulation without antigen. Ovarian activity was monitored using
      clinical observations (transrectal palpation and ultrasonography of the
      reproductive tract) in addition to blood sampling for serum progesterone and anti
      Mullerian hormone (AMH) concentrations while employing a low sampling frequency.
      Treatments and measurements were initiated in December (southern hemisphere
      summer) and subsequent data collection was performed in January, February, March
      and May. Both reZP and anti-GnRH vaccination were associated with clinically
      evident ovarian suppression in the short term. Ovarian activity in mares
      administered a reZP or anti-GnRH vaccine was significantly different to adjuvant
      control and pZP treated mares. Serum AMH concentrations were different between
      pZP and anti-GnRH treated mares 3.5 months after the final vaccination. Serum AMH
      concentrations were significantly correlated with mare age, serum progesterone
      and ovarian volume.

PMID- 30099145
TI  - Hepatitis E infection in stem cell and solid organ transplantpatients: A cross
      sectional study: The importance of HEV RNA screening in peri-transplant period.
AB  - BACKGROUND: Hepatitis E Virus (HEV) is a common cause of acute viral hepatitis
      worldwide. Typically associated with a self-limiting illness, infection may
      persist in immunosuppressed populations with significant morbidity and mortality.
      Based on clinical data published world-wide, UK blood safety guidance recommends
      the universal screening for HEV RNA of blood donors and donors of tissue, organs
      and stem cells. OBJECTIVES: This cross-sectional study aimed to determine the
      point prevalence of HEV viraemia and clinical course of viraemic patients in the
      peri-transplant period in solid organ transplant (SOT) and haematopoietic stem
      cell transplant (HSCT) recipients transplanted over a 3-year period (2013-2015).
      STUDY DESIGN: Nucleic acid extracts of whole blood from patients undergoing SOT
      or HSCT were tested by an in-house real-time reverse-transcriptase polymerase
      chain reaction assay for HEV RNA. Samples were tested at baseline (time of
      transplant), 30, 60 and 90 days post-transplant. RESULTS: 870 patients (259 HSCT,
      262 liver and 349 kidney transplant) were included with 2554 samples meeting the
      inclusion criteria. No kidney transplant patients had HEV viraemia at time of
      testing. One HSCT and three liver transplant patients were found to be HEV RNA
      positive. Overall this represented 0.46% of the patients testing positive for HEV
      viraemia. CONCLUSIONS: Prevalence of HEV viraemia in SOT and HSCT patients in
      U.K. although higher than in the general population is low at baseline and
      remains low throughout the early post-transplant phase. Clearance of viraemia can
      be maintained despite ongoing immunosuppression. Prospective U.K. studies are
      necessary to inform screening policies in this population.

PMID- 30099146
TI  - Sustainability assessments of regional water supply interventions - Combining
      cost-benefit and multi-criteria decision analyses.
AB  - To cope with present and future challenges, a growing number of water utilities
      in Sweden, Europe and elsewhere initiate various forms of inter-municipal
      cooperations creating a new regional level of drinking water governance. In order
      to reach viable decisions of alternative ways forward, there is an international
      consensus that sustainability needs to be addressed in water supply planning,
      design and decision-making. There are, however, few decision aids focusing on
      assessing the sustainability of inter-municipal cooperations and the inter
      municipal policies and interventions that regional decision-makers are faced
      with. This paper presents a decision support model based on a combination of cost
      benefit analysis and multi-criteria decision analysis for assessing the
      sustainability of regional water supply interventions, including formations of
      inter-municipal cooperations. The proposed decision support model integrates
      quantitative and semi-quantitative information on sustainability criteria. It
      provides a novel way of presenting monetized benefits and costs, capturing
      utilitarian aspects of alternative interventions, with non-monetized social and
      environmental effects, capturing aspects based in the deontological theories of
      moral ethics. The model is based on a probabilistic approach where uncertainties
      are defined by statistical probability distributions. A case study is used to
      exemplify and evaluate model application in decision situations regarding
      regionalization, (de)centralization, source water quality and redundancy. All
      evaluated alternatives were expected to contribute to a slightly improved social
      sustainability, whereas the results were more varying in the economic and
      environmental domains. A structured and transparent treatment of uncertainties
      facilitates a better understanding of the results as well as communication
      between decision-makers, stakeholders and the community.

PMID- 30099147
TI  - Exploring the critical determinants of environmentally oriented public
      procurement using the DEMATEL method.
AB  - This study explores the critical determinants of environmentally oriented public
      procurement in Singapore, and investigates the causal relationships among the
      determinants that influence this procurement. Using the extant literature and
      basing our examination on natural-resource-based theory, we develop a conceptual
      framework for the implementation of environmentally oriented public procurement
      using three high-level dimensions and ten determinants. Sixteen interviews were
      conducted with 16 senior executives working in various ministries and statutory
      boards in Singapore who are closely involved in the public-procurement process.
      The decision-making trial and evaluation laboratory (DEMATEL) method, which is a
      multicriteria decision-making tool, is employed to analyse the interview data and
      information. The results of the analysis reveal that the two most critical
      determinants for environmentally oriented public procurement in Singapore are
      energy-efficiency strategy and environmental standards. These two determinants
      were also found to be the primary drivers of the implementation of
      environmentally oriented public procurement in Singapore. Through further
      analysis using the level of influence, a cognition map is developed to illustrate
      the relationships among the ten determinants. Understanding the dynamic nature of
      public procurement through these causal relationships is essential for the
      formulation of environmentally oriented public procurement implementation
      strategies.

PMID- 30099148
TI  - Exploratory analysis of lightning-ignited wildfires in the Warren Region, Western
      Australia.
AB  - An exploratory analysis of lightning-ignited wildfire data for the Warren Region
      of Western Australia was carried out for the period from April 1976 to December
      2016. Temporal patterns in the series were examined in terms of characterizing
      the seasonal cycle, and detecting long-term trends and changes in seasonality
      over time. A generalized additive modelling approach was used to ensure that
      temporal features were determined by the data rather than a priori assumed
      mathematical forms (e.g. linear or low-order polynomial functions). The spatial
      organization of the data was evaluated using concepts from the theory of
      stochastic point processes. Results indicate a strong seasonality in the monthly
      lightning ignition series, the presence of a long-term trend and an interaction
      between trend and seasonality. There is also strong evidence of spatial variation
      in the number of ignitions per unit area in terms of location and distance from
      nearest ignition. Within the Warren Region, observation platforms for fire
      detection and reporting protocols have remained stable over the period of record,
      and changes in land use are unlikely to have altered the pattern of lightning
      ignition. Thus, the above results might reflect an interplay between: landscape
      attributes (e.g. vegetation classes, elevation, slope, aspect); changes in
      rainfall and fuel moisture; changes in fuel management practices; and, perhaps,
      an increase in the frequency of dry thunderstorms and fire weather conditions.

PMID- 30099149
TI  - Association of spasticity and motor dysfunction in chronic stroke.
AB  - BACKGROUND: The prevalence of increased muscle tone after stroke is frequently
      reported as 30% to 40%, and the condition is often concurrent with motor control
      deficits, manifesting as an inability to isolate paretic-limb joint movements.
      OBJECTIVE: The objectives of this retrospective analysis were to 1) report the
      prevalence of increased muscle tone in a convenience sample of 128 chronic stroke
      survivors with moderate/severe motor deficits and 2) quantify the relation
      between tone and motor impairment in chronic stroke survivors. METHODS: Analyses
      included descriptive statistics and multiple regression modeling, with the
      modified Ashworth Scale score (MAS; tone) as a predictor of isolated joint
      movement control (Fugl-Meyer score [FM]; motor impairment). RESULTS: Increased
      muscle tone was present in 97% of subjects. Increased muscle tone was associated
      with impaired motor control (FM; upper extremity, P=0.008; lower extremity,
      P=0.03) after adjusting for age, time since stroke and sex. We found a
      significant difference between flexor and extensor strength for finger, elbow,
      hip and knee joints (P<0.002). Participants were classified in high and low MAS
      score groups. With high MAS score and for muscles of finger flexion and forearm
      pronation, we found a trend toward impaired strength of antagonist muscles
      (finger extensors and forearm supinators, respectively) as compared with low MAS
      score for these same muscle pairings. CONCLUSIONS: The prevalence of increased
      tone was higher in this study than in previous reports. Increased muscle tone in
      chronic stroke survivors with persistent motor dysfunction could be associated
      with impaired motor control and differential muscle strength of antagonistic
      muscles.

PMID- 30099150
TI  - Analgesic gas for rehabilitation of frozen shoulder: Protocol for a randomized
      controlled trial.
AB  - BACKGROUND: There is little evidence regarding the best way to treat adhesive
      capsulitis. Physical therapy can reduce pain and improve function and range of
      motion. However, we lack clear indications on the regimen, techniques or
      intensity of physical therapy to achieve better results. Intensive physical
      therapy seems to be confined to the later stages of adhesive capsulitis (chronic
      stage) given that rehabilitation-induced pain could worsen the outcomes. Here we
      describe a protocol for a study comparing the efficacy of a standardized program
      of intensive mobilization under analgesic gas to a similar program under placebo
      gas and questioning the impact of pain. METHOD/DESIGN: A randomized, double
      blind, multicenter study - the MEOPA Trial - was designed to include adults with
      strictly defined clinical adhesive capsulitis for a 14-day intensive physical
      rehabilitation program under an equimolar mixture of oxygen and nitrous oxide or
      sham gas administration. Efficacy will be assessed by the Constant-Murley score.
      Data for secondary criteria including pain, disability, quality of life and
      perceived efficacy by the patient or physiotherapist will be collected over 6
      months. DISCUSSION: This randomized controlled trial has been designed to test
      the effectiveness of intensive physical therapy under a simple and safe analgesic
      method. This study will also address the effect of pain during rehabilitation in
      adhesive capsulitis. Furthermore, results from the 6-month multidimensional
      follow-up of painful mobilization for this condition could be extrapolated to
      other musculoskeletal conditions. TRIAL REGISTRATION: ClinicalTrials.gov No.
      NCT01087229.

PMID- 30099151
TI  - Neural multi-atlas label fusion: Application to cardiac MR images.
AB  - Multi-atlas segmentation approach is one of the most widely-used image
      segmentation techniques in biomedical applications. There are two major
      challenges in this category of methods, i.e., atlas selection and label fusion.
      In this paper, we propose a novel multi-atlas segmentation method that formulates
      multi-atlas segmentation in a deep learning framework for better solving these
      challenges. The proposed method, dubbed deep fusion net (DFN), is a deep
      architecture that integrates a feature extraction subnet and a non-local patch
      based label fusion (NL-PLF) subnet in a single network. The network parameters
      are learned by end-to-end training for automatically learning deep features that
      enable optimal performance in a NL-PLF framework. The learned deep features are
      further utilized in defining a similarity measure for atlas selection. By
      evaluating on two public cardiac MR datasets of SATA-13 and LV-09 for left
      ventricle segmentation, our approach achieved 0.833 in averaged Dice metric (ADM)
      on SATA-13 dataset and 0.95 in ADM for epicardium segmentation on LV-09 dataset,
      comparing favorably with the other automatic left ventricle segmentation methods.
      We also tested our approach on Cardiac Atlas Project (CAP) testing set of MICCAI
      2013 SATA Segmentation Challenge, and our method achieved 0.815 in ADM, ranking
      highest at the time of writing.

PMID- 30099152
TI  - Trends in Prevalence and Management of Childhood Anxiety by Australian
      Pediatricians.
AB  - OBJECTIVE: Rising anxiety rates and equity of care are ongoing concerns. Through
      2 pediatric practice audits conducted 5years apart, we aimed to determine the
      change in 1) anxiety diagnoses; 2) associated comorbid diagnoses; 3) variance in
      management by location; and 4) child, family, and pediatrician predictors of
      management. METHODS: Members of the Australian Paediatric Research Network (APRN)
      were invited to participate in patient-level prospective national pediatric
      practice audits in 2008 and 2013. Pediatricians were asked to complete
      standardized forms for 100 consecutive patients or all patients seen over 2
      weeks, whichever was completed first. Demographic data, diagnoses, medications,
      and referrals were collected. Logistic regressions were conducted, clustered at
      the pediatrician level. RESULTS: Of eligible APRN pediatricians in 2013 and 2008,
      48% and 66% participated and contributed 7102 and 8345 consultations,
      respectively. Anxiety diagnoses increased over the 5-year period (4.4% vs 7.6%; P
      < .001), as did proportions with comorbid autism spectrum disorder (18.4% vs
      29.5%; P < .001) and sleep problems (5.1% vs 9.5%; P = .02). There was an
      increase in the prescription of core anxiety medications, with prescription of
      selective serotonin reuptake inhibitors increasing from 2.0% to 27.7% (P = .01).
      Children were more likely to be referred to a psychologist if they were seen in
      metropolitan practices (odds ratio = 2.0; 95% confidence interval, 1.1-3.9; P =
      .03) or had learning difficulties (odds ratio = 2.1; 95% confidence interval, 1.1
      3.9; P = .03). CONCLUSIONS: Prevalence of anxiety among children and adolescents
      attending pediatricians nearly doubled over the 5-year period. Children in
      regional and remote locations are less likely to be referred to psychological
      services, prompting concerns about inequity in access to care.

PMID- 30099154
TI  - Effect of ursodeoxycholic acid on glycemic markers: A systematic review and meta
      analysis of clinical trials.
AB  - Ursodeoxycholic acid (UDCA) is widely used to treat liver diseases; however, its
      potential effect on metabolic parameters has been poorly investigated.
      Additionally, owing to divergent data, the objective of this meta-analysis was to
      evaluate the effect of UDCA on glycemic parameters in clinical trials. Clinical
      trials investigating the impact of UDCA treatment on glycemic markers were
      searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases
      (from inception to April 16, 2018). A random-effects model and generic inverse
      variance method were used for quantitative data synthesis. Sensitivity analysis
      was conducted using the leave-one-out method. A weighted random-effects meta
      regression was performed to evaluate the impact of potential confounders on
      glycemic parameters. Meta-analysis of seven studies comprising eight treatment
      arms revealed a significant reduction of fasting glucose levels following UDCA
      therapy (WMD: -3.30 mg/dL, 95% CI: -6.36, -0.24, p = 0.034; I2 = 28.95%). Also,
      meta-analysis of two treatment arms indicated a significant reduction of glycated
      hemoglobin (HbA1c) concentrations (WMD: -0.41% mg/dL, 95% CI: -0.81, -0.01, p =
      0.042; I2 = 0%). Additionally, meta-analysis of four treatment arms also revealed
      a significant reduction in plasma insulin levels (WMD: -1.50 mg/dL, 95% CI: 
      2.81, -0.19, p = 0.025; I2 = 67.90%) but not significant effect HOMA-IR (WMD: 
      0.20 mg/dL, 95% CI: -0.42, 0.01, p = 0.057; I2 = 85.34%). Results of this meta
      analysis showed that UDCA significantly reduces fasting plasma glucose, HbA1c,
      and insulin concentrations suggesting a positive impact on glucose homeostasis.

PMID- 30099153
TI  - Changes in vertebral dimensions in early adulthood - A 10-year follow-up MRI
      study.
AB  - Previous studies have shown that vertebral height increases until the early
      twenties, but very few studies have been conducted on other vertebral dimensions.
      Growth in vertebral size is believed to take place in elderly age but not in
      early adulthood. In this study, we wanted to clarify the potential changes in the
      dimensions of the lumbar vertebrae during early adulthood. We used the Northern
      Finland Birth Cohort 1986 as our study material, with a final sample size of 375
      individuals. We performed lumbar magnetic resonance imaging (MRI) when the
      participants were 20 and 30 years of age (baseline and follow-up, respectively).
      We recorded the width, depth, height, and cross-sectional area (CSA) of the
      fourth lumbar vertebra (L4) using the MRI scans. We used generalized estimating
      equation (GEE) models to analyse the data. Men had 7.6%-26.5% larger vertebral
      dimensions than women at both baseline and follow-up. The GEE models demonstrated
      that all the studied dimensions increased during the follow-up period among both
      sexes (p < 0.001). Men had a higher growth rate in vertebral depth and CSA than
      women (p < 0.001). Among women, small vertebral width (p = 0.001), depth (p =
      0.05) and height (p = 0.02) at baseline were associated with a higher vertebral
      growth rate during the follow-up than among those with large dimensions at
      baseline. Among men, small baseline width was associated with higher vertebral
      growth rate (p = 0.001). Our results clearly indicate that vertebral dimensions
      increase after 20 years of age among both sexes.

PMID- 30099155
TI  - Graphene oxide triggers mass transfer limitations on the methanogenic activity of
      an anaerobic consortium with a particulate substrate.
AB  - Graphene oxide (GO) is an emerging nanomaterial widely used in many manufacturing
      applications, which is frequently discharged in many industrial effluents
      eventually reaching biological wastewater treatment systems (WWTS). Anaerobic
      WWTS are promising technologies for renewable energy production through biogas
      generation; however, the effects of GO on anaerobic digestion are poorly
      understood. Thus, it is of paramount relevance to generate more knowledge on
      these issues to prevent that anaerobic WWTS lose their effectiveness for the
      removal of pollutants and for biogas production. The aim of this work was to
      assess the effects of GO on the methanogenic activity of an anaerobic consortium
      using a particulate biopolymer (starch) and a readily fermentable soluble
      substrate (glucose) as electron donors. The obtained results revealed that the
      methanogenic activity of the anaerobic consortium supplemented with starch
      decreased up to 23-fold in the presence of GO compared to the control incubated
      in the absence of GO. In contrast, we observed a modest improvement on methane
      production (>10% compared to the control lacking GO) using 5 mg of GO L-1 in
      glucose-amended incubations. The decrease in the methanogenic activity is mainly
      explained by wrapping of starch granules by GO, which caused mass transfer
      limitation during the incubation. It is suggested that wrapping is driven by
      electrostatic interactions between negatively charged oxygenated groups in GO and
      positively charged hydroxyl groups in starch. These results imply that GO could
      seriously hamper the removal of particulate organic matter, such as starch, as
      well as methane production in anaerobic WWTS.

PMID- 30099156
TI  - Alteration of bioaccumulation mechanisms of Cu by microalgae in the presence of
      natural fulvic acids.
AB  - The impact of natural fulvic acids (FAs) on the toxicity and bioaccumulation of
      Cu by Chlorella pyrenoidosa was studied. FAs extracted from Taihu Lake were
      separated into three fractions using dialysis bags: F1 (<500 Da), F2 (500-1000
      Da) and F3 (>1000 Da). The results showed that the F3 fraction with a larger
      molecular weight contained less acidic groups and unsaturated aliphatic
      structures than F1 and F2, and it showed stronger alleviation of the toxicity of
      Cu to algae. In the presence of F1~F3, the bioaccumulation curve of Cu in algae
      intersected with the straight line in the binary system of Cu-algae at
      approximately 5.3 * 10-3-6.0 * 10-3 mM of Cu equilibrium concentration, showing
      an inhibition of bioaccumulation of Cu in lower concentrations but an enhancement
      in higher Cu concentrations. The ratio of {Cu}ads/{Cu}int was used to clarify the
      transformation mechanism on adsorption; the transition interval occurred at a
      ratio of 3.5-4.4. This ratio indicated a shift from a mechanism of slow trending
      to equilibrium to a mechanism with rapid increase, which may be due to the
      bridging action of Cu to form a ternary complex of FA-Cu-algae and the occurrence
      of multilayer adsorption. The promotion order of F1> F3> F2 was consistent with
      percentages of the carboxyl group in total acidic functional groups in the FAs.
      This research is helpful for improving the accuracy of present models for the
      prediction of heavy metal risks in aqueous environments.

PMID- 30099157
TI  - What kind of effects do Fe2O3 and Al2O3 nanoparticles have on anaerobic
      digestion, inhibition or enhancement?
AB  - Fe2O3 and Al2O3 nanoparticles are widely used in products and find their way to
      wastewater treatment plants through the contact of water with these products. In
      this study, impacts of Fe2O3 and Al2O3 nanoparticles on methane potential of
      waste activated sludge (WAS) were investigated by comparing long and short term
      toxicity test results, modelling and FISH analysis. Methane production from the
      samples treated with the maximum concentration of Fe2O3 nanoparticles decreased
      28.9% at the end of the long term BMP test. EC50 value for BMP test of the Fe2O3
      nanoparticles was calculated as 901.94 mg/gTS with high coefficient of
      determination. Methane production from the samples treated with Al2O3
      nanoparticles increased up to 14.8% (p > 0.05) at the end of the BMP test.
      However, short term toxicity tests for Fe2O3 and Al2O3 nanoparticles showed no
      impact on anaerobic digestion of WAS. Kinetic parameters obtained from models and
      captured FISH images were consistent with these results. Different impacts of
      nanoparticles on methane production suggested that anaerobic microorganisms can
      be affected from nanoparticles in various mechanisms. Hydrolysis (kH) and overall
      reaction rates (kR) values were determined as 0.0277 and 0.1441 d-1, respectively
      for each concentration of Al2O3 nanoparticles and raw WAS. Similarly, methane
      production from WAS containing 5, 50, 150 and 250 mgFe2O3/gTS were modeled with
      same kinetic values. However, kH constant was calculated as 0.0149 d-1 for 500
      mgFe2O3/gTS. This means that Fe2O3 nanoparticles starting from this concentration
      inhibited the methanogenic consortium and caused decreased biogas production and
      spesific methane production rate.

PMID- 30099158
TI  - Application of fuzzy logic tools for the biogeochemical characterisation of
      (un)contaminated waters from Aljustrel mining area (South Portugal).
AB  - Aljustrel mining area (South Portugal) belongs to the Iberian Pyrite Belt (IPB).
      It is classified of high environmental risk due to its large tailings and to the
      Acid Mine Drainage (AMD) affected waters, generated by sulphides' oxidation.
      Integrating biological parameters (for the first time) in the input data matrix
      of the software PreFuRGe, allowed a better discrimination of the diatoms'
      responses to the stimuli caused by the hydrochemical changes imposed by the
      processes affecting water quality. Each hydrochemical scenario, was modeled by
      imposing maximum and minimum limits for each antecedent, according to the
      conditions imposed by the consequent, which in this case were the number of
      diatom species and pH. Thus, PreFuRGe evidenced some qualitative aspects that
      could not be achieved by classic statistics. pH appeared as the main
      discriminator of diversity and diatom species composition, nevertheless and due
      to the complex environment under study other chemical interactions must be
      considered: (a) AMD waters, with extremely low pH values, but also with extremely
      high hydrogeochemical complexity, represented by a mixture of metals, do not
      allow to associate, unequivocally, the reduction in diatom diversity to pH, but
      also to high metal (loid)s concentrations; (b) in the most alkaline waters, with
      higher abundance of diatom species, average to high concentrations of Na and Cl
      (due to Cenozoic sediments) do not seem to affect diatom diversity. This
      methodology proved to be an efficient tool to establish, for the first time,
      cause-effect relationships, improving the comprehension between biological
      (diatoms) and hydrochemical parameters.

PMID- 30099160
TI  - Perinatal exposure to nonylphenol impairs dendritic outgrowth of cerebellar
      Purkinje cells in progeny.
AB  - Nonylphenol (NP) is a commercially produced nonionic surfactant that has become a
      global environmental pollutant due to poor biodegradability. Many studies have
      confirmed that NP has detrimental effects on the central nervous system. However,
      the damaging roles of NP on the cerebellum and the underlying mechanisms remain
      unclear. Therefore, we investigated the effects of perinatal exposure to NP on
      cerebellar Purkinje cell (PC) dendrites and explored the potential mechanism
      involved. The animal model of perinatal exposure to NP was established by orally
      administering dams with either corn oil or NP (10, 50, or 100 mg/kg) during
      pregnancy and lactation. Offspring subjected to NP exposure during pregnancy and
      lactation had shorter and fewer cerebellar PC dendritic branches in childhood
      (postnatal day (PND)21) and adulthood (PND80). Contrary to expectations,
      perinatal NP treatment increased phosphorylation of protein kinase C gamma on
      PND21, but not on PND80. However, perinatal exposure to NP decreased
      phosphorylation of stathmin and tropomyosin-related kinase B (TrkB), as well as
      the expression of brain derived neurotrophic factor (BDNF) in cerebellar PCs on
      PND21 and PND80. These results indicate that perinatal exposure to NP
      irreversibly inhibited dendritic growth of PCs in the cerebella of offspring.
      Furthermore, the irreversible damage to PC dendrites in the cerebella of
      offspring subjected to perinatal NP exposure may be due to increased stathmin
      activity mediated by BDNF-TrkB signaling.

PMID- 30099159
TI  - Early chemical and toxicological risk characterization of inorganic constituents
      in surface water from the Canadian oil sands first large-scale end pit lake.
AB  - End pit lakes (EPLs) have been proposed as a method for the long-term reclamation
      of process water and fluid fine tailings (FFT) produced from surface mining
      within the Canadian oil sands. These waste products contain elevated
      concentrations of dissolved organics, metals, and salts which reduce surface
      water quality and are toxic to aquatic organisms. This study measured the
      concentrations of inorganic constituents in surface water from the industry's
      first large-scale EPL over the course of a three-year period (2014-2016). The
      toxicological risk was subsequently assessed to identify constituents of concern
      that may impair surface water quality necessary for the development of a
      functional aquatic ecosystem or for release to the surrounding environment.
      Changes in surface water concentrations over the three-year period were strongly
      correlated with hydrological processes occurring within the lake: advective
      diffusive chemical influx from FFT pore water to the overlying surface water was
      offset by efflux via continuous manual pumping (freshwater in, process water
      out). These processes resulted in a net dilution effect of approximately 5-10%
      per year, however, a significant chemical mass is expected to persist within the
      underlying FFT. Elevated salinity (as Na+, Cl-, HCO3-) and concentrations of
      boron and nickel were predicted to pose very high toxicological risk to aquatic
      organisms. Despite these risks, the discovery of wild Daphnia pulex in the August
      2016 sample suggested that surface water quality was sufficient to support
      populations of certain salt-tolerant zooplankton and primary producers. However,
      the time required for development into a robust aquatic ecosystem remains
      unknown.

PMID- 30099161
TI  - Study of the impacts of process changes of a pulp and paper mill on aerated
      stabilization basin (ASB) performance.
AB  - A laboratory scale (LS) and a field-based pilot plant (PP), designed to simulate
      aerobic stabilization basin (ASB) operation, were utilized to assess the
      potential impacts of changes in pulp and paper (P&P) mill operations on full
      scale (FS) ASB performance. Two stages of investigation were conducted. The first
      was undertaken to determine the potential of pre-alum treatment of pulp mill
      wastewaters on ASB performance. The second investigation was conducted to assess
      ASB performance where wastewaters transitioned from being coagulated pulp and
      paper mill wastewaters to paper mill wastewaters only. Simulation ASB performance
      was assessed based on removals of BOD5, colour, UV@254 nm and nutrients [total
      phosphorus (TP) and nitrogen compounds (TN)]. Pre-alum treatment of pulp mill
      wastewaters with subsequent ASB treatment following mixing with paper mill
      wastewaters showed high percentage removals of BOD5. Despite low TP
      concentrations (<=0.05 mg/L) and low nutrient to BOD5 ratios of wastewaters in
      the LS-ASB trial, the high % BOD5 removal indicated recycling of nutrients from
      sludge [sourced from the FS-ASB]. Despite coagulation of pulp mill wastewater
      being performed using a very high alum dose (~2000 mg/L) to remove colour and its
      precursors, colour formation remained high throughout the simulated ASB trials.
      Simulation of discontinuation of pulping indicated that colour would reduce
      rapidly to low levels in ASB wastewaters, but that TP and TN concentrations would
      persist for longer periods of time and decline slowly. Survey data of water
      qualities of the FS-ASB system obtained before, during and 2 years after
      discontinuation of pulping are presented.

PMID- 30099162
TI  - Assessment of natural radionuclides mobility in a phosphogypsum disposal area.
AB  - The phosphogypsum (PG) stacks located at Huelva (SW Spain) store about 100 Mt of
      PG, and covers a surface of 1000 ha. It has been very well established in many
      studies that this waste contains significant U-series radionuclides
      concentrations, with average activity concentrations rounding the 650, 600, 400
      and 100 Bq kg-1 for 226Ra, 210Po, 230Th and 238U, respectively. However, the
      radionuclide transfer from this repository into the environment by the aquatic
      pathway will depend on the mobility of each radionuclide. The mobility of the
      natural radionuclides (U-isotopes, Th-isotopes, 226Ra, and 210Po) contained in
      the PG piles were evaluated by using the optimized BCR sequential extraction
      procedure (BCR "Community Bureau of Reference"). The radionuclides were measured
      in the liquid fractions by alpha-particle spectrometry with semiconductor PIPS
      detectors. In addition, to validate the obtained results, waters from different
      locations of the PG piles (pore-water, perimeter channel and edge outflow
      leachates) were taken and the alpha emitter radionuclides determined. Uranium
      presents the highest mobility, being its total mobile fraction in the PG around
      70%, while 210Po and 226Ra present an intermediate mobility of (around 50% and
      30%, respectively). And finally, the Th-isotopes have very low mobility (mobile
      fraction < 5%), being fixed to the residual fraction. It is noteworthy that this
      behaviour has been also found in the water samples taken from the stacks,
      demonstrating that this sequential leaching operational methodology is a useful
      tool for assessing the release capacity of radionuclides by inorganic wastes.

PMID- 30099163
TI  - Ultra-low pressure membrane-based bio-purification process for decentralized
      drinking water supply: Improved permeability and removal performance.
AB  - Ultra-low pressure gravity-driven membrane (GDM) filtration has been proposed as
      a cost-efficiency alternative for the decentralized drinking water supply in
      terms of its simple operation and low energy consumptions, whereas its
      undesirable removals of dissolved organic compounds (DOC) and relatively low flux
      impede its widespread application. In order to improve its filtration
      performance, filter media (granular activated carbon (GAC), zeolite and bio
      ceramsite) was directly coated on the membrane surface to engineer an integrated
      GDM system. The coating filter layer and bio-cake layer on the membrane surface
      could engineer a highly porous "multifunctional double layer" structure, which
      facilitated improvements of stabilized flux by 30%-120% relative to GDM control.
      Besides, coating filter media to GDM can efficiently combine the complementary
      performance between filter coat and GDM filtration, and thus the removals of
      CODMn were improved to 21%, 30% and 70% in bio-ceramsite, zeolite and GAC coated
      systems. Furthermore, the integrated GDM systems conferred much higher potentials
      in resisting the shock load of contaminants (e.g. organics, ammonia, iron and
      manganese) compared to GDM control. In addition, a low-aeration cleaning in
      presence of filter media scouring could efficiently improve the flux recovery
      from 35% to 50-94%, while the membrane integrity test indicated that such filter
      media scouring would not damage the membrane surface. Overall, these findings can
      hopefully spark improvements of both permeability and permeate quality in GDM
      filtration and bring relevant benefits to the applications of GDM technologies
      for decentralized drinking water supply.

PMID- 30099164
TI  - An investigation onto Cd toxicity to freshwater microalga Chlorella sorokiniana
      in mixotrophy and photoautotrophy: A Bayesian approach.
AB  - Aquatic ecosystems are composed by a myriad of dissolved organic materials that
      can be assimilated by microalgae, while they can perform photosynthesis, this is
      refereed as mixotrophy. However, ecotoxicological tests usually consider only the
      photoautotrophic metabolism. This research investigated the ecotoxicological
      differences between photoautotrophy and mixotrophy in Chlorella sorokiniana
      exposed to cadmium (Cd). Chlorophyll a, photosynthetic efficiency (Fv/Fm), cell
      viability, biochemical composition and pH were used to monitor possible toxic
      effects at 72 h cultures. Glucose (1 g.L-1) was used as organic carbon source. To
      evaluate the probability of the photoautotrophic culture being more affected by
      Cd than the mixotrophic one, Bayesian statistical analysis was performed. The
      photoautotrophic cultures were more affected by Cd than the mixotrophic ones,
      with reduction of all evaluated parameters, except for protein concentration.
      However, in mixotrophic cultures, no changes in protein concentration and
      proteins:carbohydrates ratio were observed, and chlorophyll a, Fv/Fm and cell
      viability were only affected at the high Cd concentrations (range ln -11.5 to 
      9.4). However, both mixotrophy and photoautotrophy had the same probability of
      having the carbohydrates concentration affected by Cd. We conclude that the
      microalgae in mixotrophy were more resistant to the Cd than in photoautotrophy.
      In addition, we showed that under photoautotrophy Fv/Fm decreased linearly as Cd
      concentration increased, but in mixotrophy no effect was observed up to 10-5 molL
      1 Cd, after which it decreased. We rationale that the reduced photosynthetic
      capacity under mixotrophy can end up reducing the release of oxygen gas, which
      can compromise the entire aquatic ecosystem.

PMID- 30099165
TI  - Biosorption of lead (Pb2+) by the vegetative and decay cells and spores of
      Bacillus coagulans R11 isolated from lead mine soil.
AB  - The lead (Pb2+) bioaccumulation capacities and mechanisms of three different
      physiological structures (vegetative cells, decay cells and spores) of B.
      coagulans R11 isolated from a lead mine were examined in this study. The results
      showed that the total Pb2+ removal capacity of vegetative cells (17.53 mg/g) was
      at its optimal and higher than those of the spores and decay cells at the initial
      lead concentration of 50 mg/L. However, when the initial lead concentration
      surpassed 50 mg/L, Pb2+ removal capacity of decay cells was more efficient. Zeta
      potential, Fourier transform infrared (FTIR) and functional group modification
      analyses demonstrated that the electrostatic attraction and chelating activity of
      the functional groups were the primary pathways involved in the extracellular
      accumulation of Pb2+ by the vegetative cells and spores. However, the primary
      Pb2+ binding pathway in the decay cells was hypothesized to be due to physical
      adsorption, which easily led to Pb2+ desorption. Based on these results, we
      conclude that the vegetative cell is the ideal lead sorbent. Therefore, it is
      important to inhibit the transformation of the vegetative cells into decay cells
      and spores, which can be achieved by culturing the bacteria under anaerobic
      conditions to prevent spore formation. Heat stimulation can effectively enhance
      spore germination to generate vegetative cells.

PMID- 30099166
TI  - Presence of fluoroquinolone resistance with persistent occurrence of gyrA gene
      mutations in a municipal wastewater treatment plant in India.
AB  - Municipal wastewater treatment plants (WWTP) have been cited as the reservoirs of
      antibiotic resistance, as they provide suitable conditions for the selection of
      antibiotic resistant bacteria over the antibiotic-sensitive ones. This study is
      an attempt to investigate the occurrence of fluoroquinolone (FQ) antibiotics, FQ
      resistant bacteria in a WWTP located in India. The results indicated that the
      concentrations of FQ resistant bacteria ranged from 5.10 * 103 to 5.76 * 103
      CFU/mL in the influent stream and 2.66 * 102 to 4 * 102 CFU/mL in the effluent
      stream. An increase in the fraction of FQ resistant bacteria over the total
      bacteria is observed at the bio-outlet indicating there is a selection pressure
      within the biological treatment unit of the treatment plant. The mean
      concentrations of the FQ antibiotics, namely ciprofloxacin, norfloxacin and
      ofloxacin in the influent ranged from 6 to 16.4 MUg/L with 60-90% of removal in
      the biological treatment unit. Chlorine-based disinfection process was able to
      eliminate 96% of the FQ-resistant bacteria from the treated water being
      discharged into the river Ganges. However, the risk of horizontal gene
      transformation of resistance was found to be negligible as the resistant
      mutations occurred at Quinolone resistant determining region (QRDR) of Gyrase A
      gene. It is observed that 75% of the isolated bacteria showed two point mutations
      at S83L and D87N positions of the QRDR region of gyrA gene.

PMID- 30099167
TI  - Fluoride altered rat's blood testis barrier by affecting the F-actin via IL
      1alpha.
AB  - Fluoride is known to affect the pro-inflammatory cytokines in the testis. Most of
      the recent literatures cited that cytokines regulate the blood-testis-barrier
      (BTB). However, the involvement of cytokines in the fluoride induced toxicity in
      BTB remains unclear. In order to study this, 60 male Sprague-Dawley (SD) rats
      were taken and randomly divided into 5 groups which included four fluoride groups
      exposed to 0, 25, 50, and 100 mg/L NaF in distilled water and one positive
      control group. On the 29th day of fluoride exposure, the positive control group
      rats were administered 0.1% CaCl2 solution. Biotin tracer technology and
      transmission electron microscopy (TEM) analysis were applied to evaluate the
      function and ultra-structure of BTB. The expression levels of the BTB associated
      proteins, actin relative protein 3 (Arp3), interleukin-1 alpha (IL-1alpha), and
      transforming growth factor beta-3 (TGF-beta3) were determined using Western
      blotting and Enzyme Linked Immunosorbent Assay (ELISA) respectively, meanwhile
      the actin filament (F-actin) was detected by fluorescent phalloidin conjugates.
      Our results revealed that the function and the ultra-structure of BTB in all the
      fluoride treated groups were damaged with a concomitant significant decreases in
      basal ectoplasmic specialization (basal ES), associated protein beta-catenin, and
      F-actin. Moreover, Arp3 levels were significantly increased in 50 and 100 mg/L
      NaF groups. Meanwhile, IL-1alpha significantly increased in all the fluoride
      treated groups. In summary, we concluded that an increase in IL-1alpha induced by
      NaF significantly decreased the expression of F-actin and the organization of F
      actin highly branched, which might facilitate the BTB's functional and ultra
      structural variations.

PMID- 30099168
TI  - Effectiveness and Safety of Rivaroxaban Compared to Acenocumarol after
      Infrainguinal Surgical Revascularization.
AB  - BACKGROUND: Optimal antithrombotic therapy after lower limb infrainguinal
      revascularization remains a controversial topic. The use of anticoagulants, alone
      or in combination with antiplatelet drugs, can potentially improve patency rate
      and limb salvage, particularly in patients with risk factors for early
      thrombosis. Bleeding is the main complication of long-term anticoagulant use. New
      oral anticoagulants can represent an attractive alternative to the standard
      vitamin K antagonists. The objective of the study is to evaluate the
      effectiveness (bypass occlusion and major amputation) and safety (major bleeding
      and all-cause mortality) of rivaroxaban compared to acenocumarol after
      infrainguinal lower limb surgical revascularization. MATERIAL AND METHODS:
      Retrospective cohort study of patients with peripheral arterial disease submitted
      to lower limb infrainguinal bypass revascularization with vein or expanded
      polytetrafluoroethylene conduit, who were anticoagulated with acenocumarol or
      rivaroxaban after hospital discharge. Patients with proximal revascularization,
      revascularization due to any pathology other than peripheral arterial disease,
      coagulation disorder, stroke or acute myocardial infarction in less than 30 days,
      glomerular filtration rate <15 mL/min, or on hemodialysis were excluded. RESULTS:
      One hundred nine patients were included (78.9% male), with a mean age of 64.8
      years. After hospital discharge, 40 patients (36.7%) were medicated with
      rivaroxaban and 69 patients (63.3%) with acenocumarol. At 1 year of follow-up,
      patients under rivaroxaban and acenocumarol presented comparable major amputation
      rates (12.5 % vs. 10.1%, P = 0.756), bypass occlusion (22.5% vs. 24.6 %, P =
      0.769), and mortality rate (10% vs. 8.7%, P = 0.756). Major bleeding occurred in
      13.8% of patients. Patients with renal dysfunction had significantly higher
      bleeding risk with acenocumarol (45.5% vs. 0%, P = 0.028) compared to
      rivaroxaban, while patients with normal renal function presented similar bleeding
      rates with both anticoagulants (6.1% vs. 6.4%, P = 0.953). CONCLUSIONS:
      Rivaroxaban has equivalent effectiveness to acenocumarol after infrainguinal
      bypass revascularization, with similar occlusion, major amputation, and mortality
      rates. Rivaroxaban has an improved safety profile in patients with moderate renal
      dysfunction due to a significantly lower incidence of major bleeding. In patients
      with normal renal function, rivaroxaban and acenocumarol present equivalent major
      bleeding rates.

PMID- 30099169
TI  - Evaluation of the BASIL Survival Prediction Model in Patients Undergoing
      Infrapopliteal Interventions for Critical Limb Ischemia.
AB  - BACKGROUND: Survival prediction models are clinical tools that help professionals
      make the best treatment decisions. In the treatment of critical limb ischemia,
      several scoring methods have emerged; however, many are limited because they are
      not reproducible in different populations. This study analyze the Bypass versus
      Angioplasty in Severe Ischemia of the Leg survival prediction model (BASIL SPM),
      exclusively in patients who underwent infrapopliteal (InfraPo) revascularization
      for the treatment of critical limb ischemia. METHODS: In this retrospective
      cohort, patients who underwent InfraPo interventions during a 4-year period (2009
      2013) were consecutively included, according to the primary intervention
      (endovascular or open repair), irrespective of combined treatment in the
      femoropopliteal and InfraPo segments. Performance of the BASIL SPM was determined
      using the area under the curve of the receiver-operating characteristic curve.
      Additionally, secondary patency, limb salvage, and overall survival were analyzed
      by the Kaplan-Meier method. RESULTS: The mean follow-up duration was 32.7 +/-
      23.8 months. In the total patient group (n = 134), the mean age was 72 +/- 8.6
      years (range, 46-91 years), and the main associated comorbidities were
      hypertension (85.8%) and diabetes mellitus (76.8%). Regarding differences between
      the groups, patients in the endovascular group (n = 100) were older (73 vs. 69.5;
      P = 0.033) and more frequently stratified as high risk (61% vs. 38.2%; P = 0.030)
      than the open repair group (n = 34). The area under the curve (95% confidence
      interval [CI]) using the BASIL SPM at 6, 12, and 24 months was 0.499 (95% CI:
      0.344-0.657), 0.508 (95% CI: 0.353-0.629), and 0.549 (95% CI: 0.420-0.678),
      respectively. In the total patient group, the 36-month secondary patency, limb
      salvage, and overall survival were 31.5%, 81.1%, and 65.9%, respectively.
      CONCLUSIONS: The BASIL SPM was a poor predictor of life expectancy in this
      patient cohort.

PMID- 30099170
TI  - Cyanoacrylate Embolization: A Novelty in the Field of Varicose Veins Surgery.
AB  - In the past 2 decades, varicose veins surgery went through a great turbulence and
      various innovations. A number of new techniques have been introduced with a goal
      to increase the success rate, reduce the periprocedural complications and,
      overall, to improve patients' quality of life. The latest of them, named
      cyanoacrylate embolization (CAE) technique, threatens to shake the glory of the
      currently well-established endovenous methods. We have analyzed all previous
      studies by searching MEDLINE base using PubMed. Although the idea of using n
      butyl cyanoacrylate (NBCA) glue in medical purposes was not new, the very first
      in vivo and animal experiments using NBCA for vein closure were conducted just at
      the beginning of this millennium. The results of these studies gave warranty to
      begin with the first interventions in humans. Early studies reported very high
      success rates of more than 90%, with the longest follow-up period of 36 months.
      There were no major adverse events reported, while the minor ones-mostly
      phlebitic reactions-were defined as mild to moderate. The newest head-to-head
      studies showed that CAE is a noninferior technique to other endovenous methods,
      with higher occlusion rates and fewer adverse events. Short procedure time and no
      need for tumescent anesthesia or compressive stockings reduce patients'
      discomfort to the minimum and definitely seem to be a step forward answering the
      modern "walk in-walk out surgery" demands. As an easily handling technique, CAE
      undoubtedly pierces its path to the top of varicose veins surgery but more head
      to-head clinical trials with longer follow-up periods are necessary to obtain a
      plain picture.

PMID- 30099171
TI  - Removal of dichlorophenol by Chlorella pyrenoidosa through self-regulating
      mechanism in air-tight test environment.
AB  - Microalgae are surprisingly efficient to remove pollutants in a hermetically
      closed environment, though its growth is inhibited in the absence of pollutants.
      The final pH, algal density, Chl-a content, and the removal efficiency of 2,4
      dichlorophenol (2,4-DCP) by Chlorellar pyrenoidosa in a closed system were
      observed under different initial pH, lighting regimes, and various carbon
      sources. The optimal condition for 2,4-DCP removal was obtained, and adopted to
      observe the evolution of above items by domesticated and origin strains. The
      results showed that both respiration and photosynthesis participated in the
      degradation of 2,4-DCP, and caused the changes of pH. The photosynthesis seemed
      to increase the solution pH, while the respiration and the biodegradation of 2,4
      DCP to decrease the solution pH. The domesticated strain achieved nearly 100%
      removal when initial concentrations of 2,4-DCP lower than 200 MUg L-1, due to
      providing a appropriate but narrow pH evolution range, mostly falling between 6.5
      and 7.9. The research helps to understand the mechanism of biodegradation of
      chlorophenol compounds by green algae.

PMID- 30099172
TI  - Inventories of heavy metal inputs and outputs to and from agricultural soils: A
      review.
AB  - Heavy metal pollution of agricultural soils is an important issue around the
      world. To understand the overall pollution process, accurate determination of
      every input and output pathway of heavy metals to and from soils is essential.
      Hence, input and output inventory, a quantitative analysis method of heavy metals
      balance in agricultural soils, has been widely used. However, due to differences
      in geography, climate, socioeconomic factors, industrial and agricultural
      production, substantial variation exists among existing input and output
      inventories for different countries and regions. In this study, we systematically
      analyzed these differences and the findings will improve the compilation of
      inventories worldwide.

PMID- 30099173
TI  - Aquatic toxicity of biofuel candidates on Daphnia magna.
AB  - The increasing need for carbon-neutral, low-emission transportation sector has
      led to the development of advanced biofuels with tailor-made production and
      combustion processes. Even though the large-scale deployment of these advanced
      biofuels also increases the risk for their release into the environment, their
      toxic potency remains largely unknown. To identify hazardous biofuel candidates
      as early as possible, the fuel development process can be expanded by "Green
      Toxicology". To demonstrate such early Green Toxicology testing, this study
      investigates the aquatic toxicity for the two biofuel candidates 2
      methyltetrahydrofuran (2-MTHF) and 2-methylfuran (2-MF) on Daphnia magna. We
      performed the prolonged acute immobilisation assay (96 h) and the D. magna
      reproduction test. 2-MF induced acute effects on D. magna that were two orders of
      magnitude stronger than those of 2-MTHF. Furthermore, both substances affected
      the growth and reproductive output of D. magna in a 21 d reproduction test, with
      2-MF already inducing effects with concentrations one to two orders of magnitude
      lower than those of 2-MTHF. Thus, our assessment of the aquatic toxicity suggests
      that further biofuel development should focus on 2-MTHF. Furthermore, the acute
      immobilisation test with D. magna was identified as a promising tool for a rapid
      and sensitive "Green Toxicology" screening of further biofuel candidates.

PMID- 30099174
TI  - Understanding alcohol motivation using the alcohol purchase task: A
      methodological systematic review.
AB  - BACKGROUND: The Alcohol Purchase Task (APT) is a behavioral economic assessment
      of alcohol demand (i.e., motivation for consumption during escalating levels of
      response cost) using simulated marketplace survey techniques. While the APT is
      often used and widely cited, to date, there has yet to be a systematic review
      elucidating the variability in administering and analyzing the APT. The purpose
      of the current paper is to address this knowledge gap in the literature by
      cataloging the various purchase task methodologies and providing recommendations
      and future areas of inquiry. METHODS: The PRISMA (Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses) methodology was utilized (Prospero: No.
      CRD42017072159). Searches through Google Scholar, PsychINFO, PubMed, and
      SpringerLink databases identified 47 empirical articles referencing the use of an
      APT and published through the year 2016. Articles were coded for demographic and
      procedural characteristics, structural characteristics of the APT itself, and
      characteristics of data analysis. RESULTS: Results indicate substantial variation
      within categories and suggest that there is no standard approach to administering
      the APT or analyzing the responses generated from it. The results underscore the
      need for researchers to report as much information as possible related to
      administration, instructions, price structuring, and analytical approach, as we
      found that many articles did not provide these details. CONCLUSION: Enhancing the
      transparency of APT methods and analyses in published reports will aid in
      reproducibility as well as future meta-analytic studies of alcohol demand that
      could lead to the development of best-practice recommendations for this
      procedure.

PMID- 30099175
TI  - Comparing state, regional, and local variation in concurrent opioid and
      benzodiazepine use.
AB  - BACKGROUND: Concurrent opioid and benzodiazepine use is associated with a three
      fold increase in the risk of opioid-related overdose. No study has evaluated
      geographic variation in the concurrent use of opioids and benzodiazepines in US
      Medicare. We compared state, hospital-referral region (HRR), and county-level
      variation in concurrent opioid and benzodiazepine use among US Medicare opioid
      users and examined the heterogeneity in concurrent use within states. METHODS:
      Using 2013-2014 US Medicare Part D claims, we identified non-cancer beneficiaries
      who used opioids in 2014 (n = 268,678). The outcome was concurrent opioid and
      benzodiazepine use. We constructed logistic regression models to isolate state,
      HRR, and county-level variation not explained by patient characteristics, and
      evaluated how county and HRR quintiles are distributed within state quintiles.
      RESULTS: The adjusted probability of concurrent use ranged from 16.7%-29.6%
      across states, 12.1%-37.0% across HRRs, and 0%-65.2% across counties. State-level
      variation masks substantial county-level variation: only 18% of counties located
      in the lowest state quintile were in the lowest county quintile, and only 23% of
      counties located in the highest state quintile were in the highest county
      quintile. We also observed variation in concurrent use across HRRs within states,
      but it was not as dispersed. For example, 52% of the HRRs located in the highest
      state quintile were in the highest HRR quintile. CONCLUSIONS: Large variation in
      concurrent use of opioids and benzodiazepines exists across the US. State
      variation masks substantial local variation, which beckons for polices to monitor
      concurrent opioid and benzodiazepine use at the county level.

PMID- 30099177
TI  - Intracranial Stenting as a Rescue Therapy for Acute Ischemic Stroke After
      Stentriever Thrombectomy Failure.
AB  - OBJECTIVE: To evaluate the efficacy and safety of intracranial stenting as a
      rescue therapy for acute ischemic stroke (AIS) after stentriever thrombectomy
      failure. METHODS: Patients who received intracranial stenting as a rescue therapy
      for AIS after failure of stent retrieval with or without concomitant treatment
      between January 2014 and December 2016 were retrospectively analyzed.
      Recanalization results and outcome at 3 months were assessed, and perioperative
      complications related to the procedure were recorded. RESULTS: A total of 193
      patients with AIS received stent retriever thrombectomy. Initial successful
      recanalization with stent retriever was achieved in 125 patients. Among the 68
      patients with stent retrieval failure, 47 patients received stent placement as
      rescue therapy, and successful recanalization was achieved in 38 patients. The
      rate of successful recanalization, favorable outcome at 90 days, mortality, and
      symptomatic intracerebral hemorrhage were comparable between the stenting group
      and no-stenting group; however, the time from groin puncture to recanalization
      was significantly longer in the stenting group (P = 0.03). Compared with anterior
      circulation stroke, the rate of stent placement was significantly greater (P =
      0.041) and the intracerebral hemorrhage rate was lower in the patients with
      posterior circulation stroke who received stent placement. CONCLUSIONS:
      Intracranial stenting as a rescue therapy for AIS after failure of Solitaire
      retrieval stent is feasible and safe. AIS of posterior circulation showed greater
      intracranial stent placement than anterior circulation.

PMID- 30099176
TI  - Chronic Dilatation of Superficial Temporal Artery and Middle Meningeal Artery
      Associated with Development of Collateral Circulation After Bypass Surgery for
      Moyamoya Angiopathy.
AB  - OBJECTIVES: Dilatation of the superficial temporal artery (STA) and middle
      meningeal artery (MMA) were occasionally observed after bypass surgery for
      moyamoya angiopathy. The purpose of this study was to examine the correlation
      between angiographic outcomes and magnetic resonance imaging (MRI), specifically
      focusing on the postoperative dilatation ratio of the STA (rSTA) and MMA (rMMA).
      METHODS: Fifty-six hemispheres in 36 consecutive patients who underwent
      revascularization for moyamoya angiopathy were evaluated. All patients underwent
      angiography and MRI before surgery and during the chronic phase. Angiographic
      outcomes were classified as good or poor according to the extent of the blood
      supply through direct or indirect bypass. The rSTA and rMMA was calculated in
      time-of-flight magnetic resonance angiography (MRA). The signal changes of ivy
      signs and flow voids in basal ganglia were also evaluated. RESULTS: Postoperative
      collaterals through direct and indirect bypass was good in 30 (53.6%) and 33
      (58.9%) patients, respectively. The mean rSTA and rMMA were 36.04 +/- 28.79% and
      29.15 +/- 22.01%, respectively. Ivy signs and flow voids were decreased in 9
      (16.1%) and 26 (46.4%) patients, respectively. Univariate analyses demonstrated
      no significant correlation between the angiographic outcomes and postoperative
      signal changes on MRI. However, rSTA was significantly correlated with good
      collaterals through direct bypass (P = 0.04), whereas rMMA was significantly
      correlated with good collaterals through indirect bypass (P < 0.001).
      CONCLUSIONS: MRA may be an alternative to angiography. Both rSTA and rMMA
      estimated the development of collaterals after bypass surgery for moyamoya
      angiopathy.

PMID- 30099178
TI  - Widely Metastatic Choroid Plexus Carcinoma Associated with Novel TP53 Somatic
      Mutation.
AB  - BACKGROUND: Choroid plexus carcinoma (CPC) is a rare, malignant tumor occurring
      more commonly in children than adults. This case report describes the clinical
      course of a 3-year-old boy with a rare case of metastatic CPC with a novel TP53
      mutation. CASE DESCRIPTION: A 3-year-old boy presented with postconcussive
      symptoms after a fall. Computed tomography and magnetic resonance imaging
      revealed lesions in the suprasellar cistern, left lateral ventricle, and cauda
      equina. The tumor was diagnosed as choroid plexus carcinoma with a novel TP53
      V216M somatic mutation. The patient underwent resection of the left lateral
      ventricle lesion. CONCLUSION: We describe a case of CPC with highly metastatic
      characteristics and a novel TP53 mutation. Our report implicates TP53 in the
      pathogenesis of pediatric CPC, and we emphasize that CPC in children should
      prompt careful consideration of TP53 status to inform prognosis and clinical
      treatment.

PMID- 30099179
TI  - Perfusion Computed Tomography Parameters Are Useful for Differentiating
      Glioblastoma, Lymphoma, and Metastasis.
AB  - BACKGROUND: Perfusion computed tomography (PCT) reflects blood flow and capillary
      condition, which is valuable in assessing brain tumors. We evaluated PCT
      parameters at the tumor (t) and peritumoral (p) region to differentiate malignant
      brain tumors. METHODS: We performed PCT in 39 patients with supratentorial
      malignant brain tumors (22 glioblastomas, 6 lymphomas, 11 metastases). Regions of
      interests were placed manually at tumor, peritumoral region, and contralateral
      normal-appearing white matter. Cerebral blood volume (CBV), cerebral blood flow
      (CBF), mean transit time (MTT), and permeability surface (PS) were measured.
      These parameters were divided by those of contralateral normal-appearing white
      matter to normalize at tumor (relative [r]CBVt, rCBFt, rMTTt, rPSt) and
      peritumoral regions (rCBVp, rCBFp, rMTTp, rPSp). The parameters were evaluated
      with Mann-Whitney U test and receiver operating characteristics analyses.
      Stepwise analyses also were performed to select useful PCT parameters for
      differentiating these tumors. RESULTS: The rCBFt and rCBVt of glioblastoma (GBM)
      were greater than those of primary central nervous system lymphoma (PCNSL) (P =
      0.0005, 0.0002) and brain metastasis (METS) (P = 0.0044, 0.0028). The rMTTp of
      METS was greater than that of GBM and PCNSL (P = 0.0001, 0.0007). The combination
      of rCBVt and rPSt could differentiate GBM from other tumors with sensitivity and
      specificity of 81.8% and 94.1%. The combination of rCBFp and rMTTp could
      differentiate METS from other tumors with sensitivity and specificity of 90.9%
      and 82.1%. CONCLUSIONS: Our study introduces and supports the usefulness of PCT
      parameters for differentiation among GBM, PCNSL, and METS. rCBVt and rPSt may be
      the best predictors of GBM. rCBFp and rMTTp may be the best predictors of METS.

PMID- 30099180
TI  - Electrocardiogram-Triggered Angiography Non-Contrast-Enhanced (TRANCE) Imaging to
      Assess Access Route Before Diagnostic Cerebral Angiography.
AB  - BACKGROUND: Electrocardiogram (ECG)-triggered angiography non-contrast-enhanced
      (TRANCE) imaging is useful for investigating peripheral vessel diseases; however,
      its efficacy for access route assessment in cerebral angiography has yet to be
      reported. Therefore we aimed to evaluate the efficacy of TRANCE imaging in the
      assessment of the access route before diagnostic subtraction angiography for
      cerebral vascular disorders. METHODS: TRANCE imaging was performed in all
      patients undergoing catheter angiography for disease diagnosis at our institute
      between April 2014 and March 2015. This study included 31 patients (14 men, 17
      women) and investigated potential changes in the planned puncture site before and
      during the procedure (including the reason for the change) as our main outcome.
      RESULTS: TRANCE was successfully conducted in all of the patients recruited.
      TRANCE images led to an alteration in the approach vessel for 5 cases. The mean
      procedure time for angiography was <60 minutes. The median total number of
      catheters and guidewires used during catheter angiography was 1 (range: 1-3) and
      1 (range: 1-2), respectively. There were no catheter angiography-related
      complications. CONCLUSIONS: TRANCE imaging before diagnostic angiography is
      useful because it allows detailed assessment of the access route. This practice
      may reduce procedure time, thus resulting in fewer complications.

PMID- 30099181
TI  - Individual Surgical Strategy Using Posterior Lag Screw-Rod Technique for Unstable
      Atypical Hangman's Fracture Based on Different Fracture Patterns.
AB  - OBJECTIVE: The literature on surgical management of atypical hangman's fracture
      (AHF) is sparse. The aim of this study was to describe an individual surgical
      strategy using a lag screw-rod technique for treatment of unstable AHF based on
      different fracture patterns. METHODS: A retrospective analysis of 23 patients
      with unstable AHF was performed. Fractures were classified into 3 patterns: A, 1
      fracture line through 1 side of C2 body obliquely and another through pars
      interarticularis on the other side; B, 1 fracture line through 1 side of C2 body
      obliquely and another through contralateral lamina; C, bilateral oblique fracture
      lines through posterior cortex of C2 on different sides. Posterior C2-C3 pedicle
      screw fixation and fusion using a lag screw-rod technique with different surgical
      strategies for each fracture pattern was used for all patients. Complications,
      neck pain, neurologic status, reduction of anterior translation and angulation
      between C2 and C3, and fusion rate were evaluated. RESULTS: No technique-related
      complications (e.g., spinal cord or nerve injury caused by malposition of screws)
      occurred. Mean follow-up time was 37 months. Satisfactory reduction and bony
      union were demonstrated on postoperative radiographs. Neck pain and neurologic
      deficits caused by C2 injury improved significantly in all patients after
      operation. No graft or implant-related complications were observed in patients
      during the entire follow-up period. CONCLUSIONS: Using individual surgical
      strategies based on different fracture patterns, the posterior C2-C3 lag screw
      rod technique may be an effective and reliable option for unstable AHF.

PMID- 30099182
TI  - Biomechanical Characterization of Intracranial Aneurysm Wall: A Multiscale Study.
AB  - OBJECTIVE: Aneurysm wall biomechanics are not yet an integral part of aneurysm
      rupture risk evaluation. We aimed to develop a new technique describing the
      biomechanical properties of aneurysm wall and correlating them to rupture status.
      METHODS: Aneurysm wall samples collected during surgery were submitted before and
      after freezing to tensile tests or as fresh samples to indentation tests. The
      lateral stiffness or the Young's modulus of the different samples was determined
      as a function of the mechanical test used. The impact of freezing on
      biomechanical properties was evaluated. The correlation of clinical and
      radiologic data with the biomechanical profile of the aneurysm samples was
      investigated. Two-photon microscopy was used to study collagen fiber
      organization. RESULTS: Sixteen aneurysm samples (11 unruptured and 5 ruptured)
      were included. Freezing decreased tissue stiffness. No significant difference was
      found between ruptured and unruptured aneurysm wall samples regarding demographic
      characteristics, ethnicity, smoking status, arterial hypertension, site, size and
      shape of the aneurysm, PHASES score, mechanical profile, or overall Young's
      modulus. Indentation tests found that the rupture occurred in a restricted area
      of increased elastic capacity and unruptured areas had increased stiffness. Two
      photon microscopy found disruption of the collagen fiber network in rupture
      zones. CONCLUSIONS: The indentation test of fresh aneurysm wall samples described
      the heterogeneity of biomechanical properties of the tissue and found increased
      elastic capacity in the rupture zone and increased stiffness in the remainder of
      the aneurysm. This study could be a basis for further research aimed at building
      a biomechanical-based model of aneurysm rupture risk.

PMID- 30099183
TI  - Intracranial Rosai-Dorfman Disease Involving the Cavernous Sinus: A Case Report
      and Review of the Literature.
AB  - BACKGROUND: Rosai-Dorfman disease (RDD), also called sinus histiocytosis with
      massive lymphadenopathy, is an idiopathic, non-neoplastic, lymphoproliferative
      disorder. Histologically, the disease is characterized by emperipolesis and S-100
      immunoreactivity. RDD usually presents with massive painless cervical
      lymphadenopathy, with only 5% of cases affecting the central nervous system. CASE
      DESCRIPTION: We report the case of a 46-year-old woman with isolated RDD of the
      left cavernous sinus with left facial numbness and weakness of the left
      masticatory muscle. The patient was successfully treated by total resection
      without recurrence found at the 65-month follow-up examination. CONCLUSIONS:
      Central nervous system RDD is a diagnostic challenge preoperatively depending on
      the radiologic findings. Immunohistochemical confirmation is indispensable for
      the definite diagnosis. Total resection remains the most effective treatment to
      date. Adjuvant treatment such as chemotherapy, radiotherapy, and steroids can be
      administrated in cases of incomplete resection, recurrence, or multiple foci.

PMID- 30099184
TI  - Stereotactic Radiosurgery for Trigeminal Schwannomas: A 28-Year Single-Center
      Experience and Review of the Literature.
AB  - OBJECTIVE: To assess outcomes and complications of stereotactic radiosurgery
      treatment for trigeminal schwannoma (TS). METHODS: A retrospective analysis was
      performed to describe the presentation and outcomes of patients undergoing Gamma
      Knife radiosurgery (GKRS) for TS. Clinical, radiographic, and stereotactic
      radiosurgery dose plans were reviewed. Descriptive statistics and univariate
      analysis were performed to identify factors associated with poor tumor control.
      RESULTS: A total of 22 patients with TS were treated with GKRS between 1990 and
      2018. One patient had a history of neurofibromatosis type II. Of the study
      population, 81% underwent GKRS as a first-line treatment. The average tumor
      volume was 3.3 cm3 and the average margin treatment dose was 14.1 Gy. The median
      clinical and radiographic follow-up period were 18.5 and 27 months, respectively.
      Tumor control was achieved in 17 patients (77.3%). Symptomatic improvement was
      noted in 8 patients (42.1%). Tumor expansion was observed in 7 patients (31.8%)
      and was associated with poor tumor control at last follow-up (P < 0.05). Patients
      who developed transient tumor expansion had higher margin doses (14.9 +/- 1.1 Gy)
      compared with patients who did not have expansion (13.6 +/- 1.3 Gyk P < 0.05).
      CONCLUSIONS: GKRS provides effective control for most TS. Increased margin doses
      are associated with tumor expansion, which was a poor prognostic event associated
      with progression and clinical decline. Based on these results, combined with
      analysis of available data from other series of TS treated with GKRS, we believe
      that margin dose between 13 and 14 Gy offers a high probability of tumor control,
      yet minimizing risk of adverse radiation effects.

PMID- 30099185
TI  - Hybrid Operation of a Ruptured Aneurysm Associated with a Developmental Venous
      Anomaly.
AB  - BACKGROUND: As a normal variation of the cerebral venous angioarchitecture,
      developmental venous anomalies (DVAs) represent a rare cause of intraparenchymal
      hemorrhage. Different from mixed vascular lesions, such as capillary
      malformations, arteriovenous malformations, arteriovenous fistulas, and
      thrombosis, here we describe the first case of a ruptured hemodynamic aneurysm
      associated with a DVA and introduce the first use of hybrid operation for the
      treatment of a hemorrhagic DVA. METHODS: A 14-year-old girl suffered from sudden
      onset of headache, aphasia, and left hemiplegia. On the way of her transfer to
      our center, she suddenly fell into a coma. Computed tomography scan demonstrated
      an enlarged intraparenchymal hemorrhage in the left temporal lobe. Angiography
      revealed a large frontal DVA with an associated hemodynamic aneurysm.
      Superselective angiography of left middle cerebral artery confirmed that the
      aneurysm was located on the turning site of arteriovenous transition. RESULTS:
      Considering the large hematoma and the possible occlusion of surrounding
      collecting veins, we attempted transarterial embolization but were unsuccessful.
      Hematoma evacuation and aneurysm isolation were performed in a hybrid operation
      room. Intraoperative angiography was used to confirm the location of the aneurysm
      and to recheck the result. The patient woke up 1 day later and the symptoms were
      relieved entirely 1 year later. CONCLUSIONS: Associated aneurysm may be a cause
      of intraparenchymal hemorrhage in DVAs and routine imaging monitoring is needed.
      Hybrid operation is a possible treatment for such complicated mixed lesions in
      DVA, which proved to be safe and effective in this patient.

PMID- 30099186
TI  - The 100 Most-Cited Reports About Craniopharyngioma.
AB  - OBJECTIVE: Our objective was to identify the 100 most-cited research reports on
      craniopharyngiomas. METHODS: The Thomson Reuters Web of Science service was
      queried for the years 1900 to 2017 without language restrictions. The articles
      were sorted in descending order of the number of times they had been cited by
      other studies, and all titles and abstracts were screened to identify the
      research areas of the top 100 reports. The number of citations per year was
      calculated. RESULTS: We identified the 100 most-cited articles on
      craniopharyngioma, which, collectively, had been cited 20,994 times at the time
      of our report. The top cited report had been cited 718 times, with an average of
      144 citations annually since publication. The oldest article had been published
      in 1969 and the most recent in 2013; the most prolific decade was the 2000s, with
      38 of the included articles published during that period. Thirty-two unique
      journals contributed to the 100 articles, with the Journal of Neurosurgery
      contributing most of the articles (n = 31). The most common country of article
      origin was the United States (n = 49), followed by United Kingdom (n = 12),
      Germany (n = 10), and Italy (n = 6). CONCLUSIONS: The present study identified
      the 100 most-cited research articles in craniopharyngioma. These results
      highlight the multidisciplinary and multimodal nature of craniopharyngioma
      management. Recognition of important historical contributions to this field could
      guide future investigations.

PMID- 30099187
TI  - Clinical and Radiologic Outcomes of Direct Versus Indirect Decompression with
      Lumbar Interbody Fusion: A Matched-Pair Comparison Analysis.
AB  - OBJECTIVE: To compare the radiologic and clinical outcomes between oblique lumbar
      interbody fusion (OLIF) without laminectomy and minimally invasive transforaminal
      lumbar interbody fusion (MI-TLIF). METHODS: This was a retrospective study.
      Between April 2012 and January 2017, 25 patients in each of the MI-TLIF and OLIF
      groups were recruited as matched pairs. Clinical outcomes included visual
      analogue scale, Oswestry Disability Index, and satisfaction rates. Radiographic
      outcomes comprised disc height (DH) and fusion status. Intraoperative data and
      complications were collected. All patients completed the clinical and radiologic
      outcomes. Outcomes were compared preoperatively and postoperatively. RESULTS:
      Matched pairs were compared between 2 groups in terms of demographic data and
      preoperative measurements; less blood loss and shorter operative time were found
      in OLIF versus MI-TLIF (P < 0.001). The total complication rate was 36% in OLIF
      and 32% in MI-TLIF (P = 0.77). The outcomes of visual analogue scale and Oswestry
      Disability Index were significantly improved in both groups, and there was no
      significant difference between 2 groups. Satisfaction rates of the both groups
      were more than 90%. OLIF was superior to MI-TLIF with respect its capability to
      restore DH (P < 0.001). Earlier time of fusion was observed in OLIF (80%)
      compared with MI-TLIF (52%) at 6 months (P = 0.04). CONCLUSIONS: OLIF may achieve
      equivalent clinical and radiologic outcomes compared with MI-TLIF when the
      stenosis is minimal because the decompression performed is indirect. Furthermore,
      the OLIF shows less blood loss and shorter operative time, better restoration of
      DH, and earlier time to fusion than the MI-TLIF.

PMID- 30099188
TI  - Effect of Bone Flap Surface Area on Outcomes in Decompressive Hemicraniectomy for
      Traumatic Brain Injury.
AB  - BACKGROUND: Decompressive hemicraniectomy to control medically refractory
      intracranial hypertension and cerebral edema and evacuate mass lesions in
      traumatic brain injury is a widely accepted treatment paradigm. However, the
      critical specifications of the bone flap size necessary to control the
      intracranial pressure (ICP) and provide improved patient outcomes is unknown. We
      assessed the effect of craniectomy size on the outcomes in surgical decompression
      for traumatic brain injury. METHODS: From 2003 to 2011, 58 cases of decompressive
      hemicraniectomy were performed for evacuation of hematoma and treatment of
      refractory ICP in adult patients with traumatic brain injury. The surface area of
      the decompressive bone flaps was calculated from the postoperative computed
      tomography scans and correlated with the ICP and Glasgow Coma Scale scores
      immediately postoperatively and during long-term follow-up. RESULTS:
      Decompressive craniectomy led to a statistically significant continued reduction
      in the preoperative ICP values (24.5 mm Hg; range, 5-30 mm Hg) compared with the
      postoperative ICP (16.7 mm Hg; range, 1-30; P = 0.006). However, no significant
      improvement in the preoperative Glasgow Coma Scale (7.47 mm Hg; range, 3-15; vs.
      7.50 mm Hg; range, 3-15; P = 0.96) was observed with hemicraniectomy. CONCLUSION:
      For surface areas of 7000-16,000 mm2, size was an independent factor in ICP
      reduction but not for the overall neurologic outcome.

PMID- 30099189
TI  - Cerebrospinal Fluid Leak in Juvenile Nasopharyngeal Angiofibroma-Rare Sequelae of
      Flutamide-Induced Tumor Shrinkage.
AB  - BACKGROUND: Nonsteroidal androgen receptor blockers like flutamide have been
      described as an adjuvant treatment for preoperative shrinkage of extensive
      juvenile nasopharyngeal angiofibroma. We present a case of cerebrospinal fluid
      (CSF) leak due to flutamide-induced tumor shrinkage. CASE REPORT: A 15-year-old
      male with a prior diagnosis of juvenile nasopharyngeal angiofibroma stage IIIB on
      preoperative flutamide for 3.5 weeks presented with altered sensorium, meningeal
      signs, and clear watery nasal discharge consistent with CSF leak. Computed
      tomogram of the head revealed air in the ventricle and repeat contrast-enhanced
      magnetic resonance imaging showed significant tumor shrinkage in the area of the
      anterior skull base. This patient had an atypical pattern of tumor extension into
      the anterior skull base through the roof of posterior ethmoid and sphenoid sinus,
      which are inherently weak areas of the skull base, thereby predisposing the CSF
      leak on tumor shrinkage. CONCLUSION: CSF leak is a rare complication following
      flutamide therapy, especially if large areas of the anterior skull base are
      involved.

PMID- 30099190
TI  - Continuous and Dynamic Facial Nerve Mapping During Surgery of Cerebellopontine
      Angle Tumors: Clinical Pilot Series.
AB  - OBJECTIVE: To evaluate a new surgical tool combining suction and monopolar
      neurostimulation (stimulation sucker) for cerebellopontine angle (CPA) tumors.
      The usefulness for continuous (time) and dynamic (space) facial nerve mapping was
      studied. METHODS: Patients operated on with the stimulation sucker for a CPA
      tumor between April 2016 and May 2017 in a tertiary care center were identified.
      Clinical charts were retrospectively evaluated. The minimum follow-up time of
      patients was 12 months. RESULTS: The study population included 17 patients with
      tumor (6 women and 11 men). The age range was from 2 to 77 years (mean age, 45.7
      years; standard error of the mean, 22.7 years). Most CPA tumors were large (Koos
      grade 4) vestibular schwannomas (n = 10); other pathologies included petrous
      meningioma (n = 1), metastasis (n = 1), medulloblastoma (n = 2), ependymoma (n =
      2), and pilocytic astrocytoma (n = 1). One patient with trigeminal neuralgia
      served as the normal control subject. No complications because of the stimulation
      sucker were encountered. Clinical and radiologic outcomes compared favorably with
      institutional experience and literature. The stimulation sucker allowed for
      continuous (time) mapping of the facial nerve at the site of resection (space).
      This real-time feedback allowed early identification of the facial nerve.
      Handling and ergonomy were excellent and workflow improved. The shortcomings
      compared with a bayonet-shaped bipolar probe were decreased visibility of
      neurovascular structures and lower spatial discrimination. The new device did not
      simplify delicate at the brainstem and on the nerve. We think it should be
      considered as a complementary tool in the surgeon's armamentarium. CONCLUSIONS:
      Until now, nerve damage as assessed by neuromonitoring (e.g., facial nerve
      electromyography, motor evoked potential) served as surrogate for nerve function.
      This concept should be challenged. The studied stimulation sucker detected the
      facial nerve earlier than conventional techniques, preventing harm by surgical
      trauma. A larger, prospective study is warranted to better define its role in CPA
      surgery.

PMID- 30099191
TI  - Sex-Specific Trends in Incidence and Mortality for Urban and Rural Ambulatory
      Patients with Heart Failure in Eastern Ontario from 1994 to 2013.
AB  - BACKGROUND: Differences in outcomes have previously been reported between urban
      and rural settings across a multitude of chronic diseases. Whether these
      discrepancies have changed over time, and how sex may influence these findings is
      unknown for patients with ambulatory heart failure (HF). We examined the temporal
      incidence and mortality trends by geography in these patients. METHODS AND
      RESULTS: We conducted a retrospective cohort study of 36,175 eastern Ontario
      residents who were diagnosed with HF in an outpatient setting from 1994 to 2013.
      The primary outcome was 1-year mortality. We examined temporal changes in
      mortality risk factors with the use of multivariable Cox proportional hazard
      models. The incidence of HF decreased in women and men across both rural and
      urban settings. Age-standardized mortality rates also decreased over time in both
      sexes but remained greater in rural men compared with rural women. CONCLUSIONS:
      The incidence of HF in the ambulatory setting was greater for men than women and
      greater in rural than urban areas, but mortality rates remained higher in rural
      men compared with rural women. Further research should focus on ways to reduce
      this gap in the outcomes of men and women with HF.

PMID- 30099192
TI  - Validation and Recalibration of Seattle Heart Failure Model in Japanese Acute
      Heart Failure Patients.
AB  - BACKGROUND: Precise risk stratification in heart failure (HF) patients enables
      clinicians to tailor the intensity of their management. The Seattle Heart Failure
      Model (SHFM), which uses conventional clinical variables for its prediction, is
      widely used. We aimed to externally validate SHFM in Japanese HF patients with a
      recent episode of acute decompensation requiring hospital admission. METHODS AND
      RESULTS: SHFM was applied to 2470 HF patients registered in the West Tokyo Heart
      Failure and National Cerebral And Cardiovascular Center Acute Decompensated Heart
      Failure databases from 2006 to 2016. Discrimination and calibration were assessed
      with the use of the c-statistic and calibration plots, respectively, in HF
      patients with reduced ejection fraction (HFrEF; <40%) and preserved ejection
      fraction (HFpEF; >=40%). In a perfectly calibrated model, the slope and intercept
      would be 1.0 and 0.0, respectively. The method of intercept recalibration was
      used to update the model. The registered patients (mean age 74 +/- 13 y) were
      predominantly men (62%). Overall, 572 patients (23.2%) died during a mean follow
      up of 2.1years. Among HFrEF patients, SHFM showed good discrimination (c
      statistic = 0.75) but miscalibration, tending to overestimate 1-year survival
      (slope = 0.78; intercept = -0.22). Among HFpEF patients, SHFM showed modest
      discrimination (c-statistic = 0.69) and calibration, tending to underestimate 1
      year survival (slope = 1.18; intercept = 0.16). Intercept recalibration
      (replacing the baseline survival function) successfully updated the model for
      HFrEF (slope = 1.03; intercept = -0.04) but not for HFpEF patients. CONCLUSIONS:
      In Japanese acute HF patients, SHFM showed adequate performance after
      recalibration among HFrEF patients. Using prediction models to tailor the care
      for HF patients may improve the allocation of medical resources.

PMID- 30099193
TI  - Assessment of Congestion in Acute Heart Failure: When Simplicity Does Not Go
      Along With Accuracy.

PMID- 30099194
TI  - MyD88 signaling in T regulatory cells by endogenous ligands dampens skin
      inflammation in filaggrin deficient mice.
AB  - Mutations in filaggrin are associated with atopic dermatitis. Filaggrin-deficient
      flaky tail (Flgft/ft) mice develop spontaneous inflammatory skin lesion that wax
      and wane. We show that loss of MyD88 promotes the persistence of skin lesions in
      Flgft/ft mice and exaggerates their expression of the Th17-associated cytokines
      Il7a and Il22. The development and persistence of skin lesions in Flgft/ft mice
      was independent of the microbiota. MyD88-mediated signals are shown to be
      important for the accumulation of T regulatory cells (Tregs) in lesional skin of
      Flgft/ft mice. Adoptive transfer of WT Tregs dampened the severity of skin
      lesions in MyD88-/-/Flgft/ft mice. These results suggest that MyD88 signaling in
      Treg cells by endogenous ligands attenuates skin inflammation in filaggrin
      deficiency.

PMID- 30099195
TI  - Expression and DNA methylation analysis of cyp19a1a in Chinese sea perch
      Lateolabrax maculatus.
AB  - Cytochrome P450 aromatase (P450arom), which is encoded by cyp19a1a, can convert
      androgen to estrogen. Therefore, P450arom is important in gonadal differentiation
      and maintenance. In this study, we analyzed the expression and DNA methylation of
      cyp19a from Chinese sea perch Lateolabrax maculatus (sp. cyp19a1a). The sp.
      cyp19a1a gene consists of 9 exons, but only 3.5 kb, being smaller than the human
      cyp19a1a, as a result of small introns. The sp. cyp19a1a protein contains 518
      amino acid residues and evolutionarily conserved domains and is clustered in the
      teleost subfamily on the phylogenetic tree. Amino acid alignment indicates that
      sp. cyp19a1a shares the highest identity (91.6%) to Epinephelus akaara and Lates
      calcarifer. Endogenous sp. cyp19a1a is detected mainly in stromal cells around
      the oocytes of stage I ovary, and the gene expression level has no difference
      after 40 days fresh water culture in both ovary and testis. The sp. Cyp19a1a can
      catalyze the production of estrogen from androgen in vitro. Seven CpG
      dinucleotides are found in the proximal promoter. Binding sites of the conserved
      predicted transcription factors include cAMP response element, steroidogenic
      factor-1, and SRY-Box. The deletion of this region reduces promoter activity
      significantly. The methylation level of the seven CpG dinucleotides in cyp19a1a
      promoter is higher in the testis (44.25 +/- 4.04) than in the ovary (24.71 +/-
      3.05). The induced hypermethylation of the sp. cyp19a1a promoter suppressed
      promoter transcription function in vitro. These results suggest that DNA
      methylation may be a mechanism used for natural sex maintenance.

PMID- 30099196
TI  - Effects of short-term fasting on the rhythmic expression of core circadian clock
      and functional genes in skeletal muscle of goldfish (Carassius auratus).
AB  - Molecular oscillators exist in peripheral tissues like pacemaker cells. Food
      intake is a dominant zeitgeber for peripheral clocks in vertebrates. Fasting is a
      physiological stress that elicits well-known metabolic adaptations, however,
      little is known about the effects of the rhythmic expression of clock components
      in skeletal muscle following short-term fasting in goldfish. Here, we
      characterized the molecular clock components and their daily transcription in
      COSINOR, and assessed the effect of 7-day fasting on the circadian patterns of
      the candidate genes expression in goldfish skeletal muscle. For the core clock
      genes, clock, bmal1a, cry1, cry2, cry3, per1, per2 and per3 showed circadian
      rhythmicity in fed goldfish, but not for bmal1a, cry2 and per1 in the fasted
      state. Of the 8 candidate functional genes analyzed, igf1, igf2 and igfbp2 showed
      circadian rhythmicity in the fed state, but circadian pattern was only observed
      for mRNA of myog, igfbp2 and mstn in fasted goldfish. Additionally, Spelman's
      correlation analysis showed the circadian expression of the myog and mstn
      presented positive and negative correlation with the transcription pattern of
      clock and per2 genes in fasted goldfish, respectively. Our results demonstrated
      that the peripheral clocks might be reset to respond rapidly to withholding of
      food in teleost skeletal muscle.

PMID- 30099197
TI  - Toxicological assessment of additively manufactured methacrylates for medical
      devices in dentistry.
AB  - : The paucity of information on the biological risks of photopolymers in additive
      manufacturing is a major challenge for the uptake of the technology in the
      construction of medical devices in dentistry. In this paper, the biocompatibility
      of methacrylates for denture bases, splints, retainers and surgical guides were
      evaluated using the innovative zebrafish embryo model, which is providing a high
      potential for toxicity profiling of photopolymers and has high genetic similarity
      to humans. Toxicological data obtained confirmed gradations of toxicity
      influenced by ethanol treatment, exposure scenarios and extraction vehicles. In
      direct exposure tests, juvenile fish exposed to non-treated methacrylates in
      ultrapure water showed accelerated toxicity endpoints compared to fish in
      transparent E3 medium. Similarly, toxic extracts induced mostly acute responses
      (embryonic mortality) in contrast to cumulative chronic (sublethal and
      teratogenic effects) in direct exposure. Methacrylates composed of >60%
      Ethoxylated bisphenol A dimethacrylate produced a relatively lower conversion
      rate in FTIR spectroscopy, but were safe in zebrafish bioassays after ethanol
      treatment. The study affirms that biocompatibility was influenced primarily by
      physico-chemical characteristics of the materials, which subsequently influenced
      their residual monomer content before and after immersion in ethanol. Given the
      precautionary implications of the study, we propose a 3-tiered approach i.e.
      using approved materials, apposite manufacturing parameters and post-processing
      techniques that together guarantee optimal results for medical devices. STATEMENT
      OF SIGNIFICANCE: This study is timely and relevant since there is limited
      published literature that precisely describes the toxicological properties of
      additively manufactured methacrylates despite their increased popularity for
      medical devices. While it is generally accepted that the zebrafish excels as a
      model system for developmental toxicity, a further examination of its utility in
      this study using different protocols provides basis for its consideration and
      adoption at a crucial time when there is a lack of consensus regarding the most
      suited biological assessment methods for medical devices.

PMID- 30099198
TI  - Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic
      pancreatic tumor complexity.
AB  - : The preclinical drug screening of pancreatic cancer treatments suffers from the
      absence of appropriate models capable to reproduce in vitro the heterogeneous
      tumor microenvironment and its stiff desmoplasia. Driven by this pressing need,
      we describe in this paper the conception and the characterization of a novel 3D
      tumor model consisting of a triple co-culture of pancreatic cancer cells (PANC
      1), fibroblasts (MRC-5) and endothelial cells (HUVEC), which assembled to form a
      hetero-type multicellular tumor spheroid (MCTS). By histological analyses and
      Selective Plain Illumination Microscopy (SPIM) we have monitored the spatial
      distribution of each cell type and the evolution of the spheroid composition.
      Results revealed the presence of a core rich in fibroblasts and fibronectin in
      which endothelial cells were homogeneously distributed. The integration of the
      three cell types enabled to reproduce in vitro with fidelity the influence of the
      surrounding environment on the sensitivity of cancer cells to chemotherapy. To
      our knowledge, this is the first time that a scaffold-free pancreatic cancer
      spheroid model combining both tumor and multiple stromal components has been
      designed. It holds the possibility to become an advantageous tool for a pertinent
      assessment of the efficacy of various therapeutic strategies. STATEMENT OF
      SIGNIFICANCE: Pancreatic tumor microenvironment is characterized by abundant
      fibrosis and aberrant vasculature. Aiming to reproduce in vitro these features,
      cancer cells have been already co-cultured with fibroblasts or endothelial cells
      separately but the integration of both these essential components of the
      pancreatic tumor microenvironment in a unique system, although urgently needed,
      was still missing. In this study, we successfully integrated cellular and
      acellular microenvironment components (i.e., fibroblasts, endothelial cells,
      fibronectin) in a hetero-type scaffold-free multicellular tumor spheroid. This
      new 3D triple co-culture model closely mimicked the resistance to treatments
      observed in vivo, resulting in a reduction of cancer cell sensitivity to the
      anticancer treatment.

PMID- 30099199
TI  - Solution fibre spinning technique for the fabrication of tuneable decellularised
      matrix-laden fibres and fibrous micromembranes.
AB  - : Recreating tissue-specific microenvironments of the extracellular matrix (ECM)
      in vitro is of broad interest for the fields of tissue engineering and organ-on-a
      chip. Here, we present biofunctional ECM protein fibres and suspended membranes,
      with tuneable biochemical, mechanical and topographical properties. This soft and
      entirely biologic membrane scaffold, formed by micro-nano-fibres using low
      voltage electrospinning, displays three unique characteristics for potential cell
      culture applications: high-content of key ECM proteins, single-layered mesh
      membrane, and flexibility for in situ integration into a range of device setups.
      Extracellular matrix (ECM) powder derived from urinary bladder, was used to
      fabricate the ECM-laden fibres and membranes. The highest ECM concentration in
      the dry protein fibre was 50 wt%, with the rest consisting of gelatin. Key ECM
      proteins, including collagen IV, laminin, and fibronectin, were shown to be
      preserved post the biofabrication process. The single fibre tensile Young's
      modulus can be tuned for over two orders of magnitude between ~600 kPa and 50 MPa
      depending on the ECM content. Combining the fibre mesh printing with 3D printed
      or microfabricated structures, culture devices were constructed for endothelial
      layer formation, and a trans-membrane co-culture formed by glomerular cell types
      of podocytes and glomerular endothelial cells, demonstrating feasibility of the
      membrane culture. Our cell culture observation points to the importance of
      membrane mechanical property and re-modelling ability as a factor for soft
      membrane-based cell cultures. The ECM-laden fibres and membranes presented here
      would see potential applications in in vitro assays, and tailoring structure and
      biological functions of tissue engineering scaffolds. STATEMENT OF SIGNIFICANCE:
      Recreating tissue-specific microenvironments of the extracellular matrix (ECM) is
      of broad interest for the fields of tissue engineering and organ-on-a-chip. Both
      the biochemical and biophysical signatures of the engineered ECM interplay to
      affect cell response. Currently, there are limited biomaterials processing
      methods which allow to design ECM membrane properties flexibly and rapidly.
      Solvents and additives used in many existing processes also induced unwanted ECM
      protein degradation and toxic residues. This paper presents a solution fibre
      spinning technique, where careful selection of the solution combination led to
      well-preserved ECM proteins with tuneable composition. This technique also
      provides a highly versatile approach to fabricate ECM fibres and membranes,
      leading to designable fibre Young's modulus for over two orders of magnitude.

PMID- 30099200
TI  - Size-dependent neutralizing activity of gold nanoparticle-based subunit vaccine
      against dengue virus.
AB  - : Dengue results in substantial human morbidity and significant socio-economic
      impacts, but a specific dengue therapeutic is not available. The currently
      available dengue vaccine has low efficacy and high rate of adverse effects,
      necessitating different strategies for the development of a safer and more
      efficient vaccine against dengue virus. We describe here a hybrid combination of
      different-sized gold nanoparticles (AuNPs) and domain III of envelope
      glycoprotein derived from serotype 2 of dengue virus (EDIII) as dengue subunit
      vaccine. The efficacy of the EDIII-functionalized AuNPs (AuNP-E) to induce
      neutralizing antibody in BALB/c mice is evaluated. Obtained results show that
      AuNP-E induced a high level of antibody which mediates serotype-specific
      neutralization of dengue virus. More importantly, the level of antibody is
      dependent on both the size of AuNPs and the concentration of AuNP-E, implicating
      the possibility to modulate it through adjusting these parameters. These results
      represent an important step towards the development of tetravalent AuNP-based
      subunit dengue vaccine. STATEMENT OF SIGNIFICANCE: This research presents a novel
      subunit vaccine against dengue virus using a hybrid comprising gold nanoparticles
      (AuNPs) and domain III of envelop protein (EDIII). We proved the neutralizing
      activity of anti-EDIII antibody induced in immunized mice on Dengue virus
      serotype 2 in an AuNP core size and concentration dependent manner. The hybrid
      concept behind this work could also be adopted for the development of a
      tetravalent vaccine against four serotypes of Dengue virus.

PMID- 30099201
TI  - Tailoring the subchondral bone phase of a multi-layered osteochondral construct
      to support bone healing and a cartilage analog.
AB  - : Focal chondral and osteochondral defects create significant pain and disability
      for working-aged adults. Current osteochondral repair grafts are limited in
      availability and often fail due to insufficient osseous support and integration.
      Thus, a need exists for an off-the-shelf osteochondral construct with the
      propensity to overcome these shortcomings. Herein, a scalable process was used to
      develop a multi-layered osteochondral graft with a subchondral bone (ScB) phase
      tailored to support bone healing and integration. Multiple ScB formulations and
      fabrication techniques were screened via degradation, bioactivity, and unconfined
      compression testing. An optimized ScB construct was selected and its cytotoxicity
      assessed. Additionally, a cartilage analog was secured to the optimized ScB
      construct via a calcified cartilage layer, and the resulting osteochondral
      construct was characterized via interfacial shear and dynamic mechanical testing.
      The optimized ScB construct did not significantly alter local pH during
      degradation, exhibited measurable bioactivity in vitro, and had significantly
      greater compressive mechanical strength compared to other constructs. The
      attachment strength of the cartilage analog was significantly greater by an
      increase in compressive dynamic mechanical properties. Furthermore, this ScB
      construct was found to be cytocompatible with human bone marrow-derived
      mesenchymal stromal cells. Taken together, this optimized ScB material forms the
      robust foundation of a novel, off-the-shelf osteochondral construct to be used in
      defect repair. STATEMENT OF SIGNIFICANCE: The quality of life for millions of
      individuals worldwide is detrimentally affected by focal chondral or
      osteochondral defects. Current off-the-shelf biomaterial constructs often fail to
      repair these defects due to insufficient osseous support and integration. Herein,
      we used a scalable process to fabricate and optimize a novel boney construct.
      This optimized boney construct demonstrated biochemical, physical, and mechanical
      properties tailored to promote bone healing. Furthermore, a novel cartilage
      analog was successfully attached to the boney construct, forming a multi-layered
      osteochondral construct.

PMID- 30099202
TI  - Choline ameliorates adult learning deficits and reverses epigenetic modification
      of chromatin remodeling factors related to adolescent nicotine exposure.
AB  - Earlier initiation of smoking correlates with higher risk of nicotine dependence,
      mental health problems, and cognitive impairments. Additionally, exposure to
      nicotine and/or tobacco smoke during critical developmental periods is associated
      with lasting epigenetic modifications and altered gene expression. This study
      examined whether adolescent nicotine exposure alters adult hippocampus-dependent
      learning, involving persistent changes in hippocampal DNA methylation and if
      choline, a dietary methyl donor, would reverse and mitigate these alterations.
      Mice were chronically treated with nicotine (12.6 mg/kg/day) starting at post
      natal day 23 (pre-adolescent), p38 (late adolescent), or p54 (adult) for 12 days
      followed by a 30-day period during which they consumed either standard chow or
      chow supplemented with choline (9 g/kg). Mice then were tested for fear
      conditioning and dorsal hippocampi were dissected for whole genome methylation
      and selected gene expression analyses. Nicotine exposure starting at p21 or p38,
      but not p54, disrupted adult hippocampus-dependent fear conditioning. Choline
      supplementation ameliorated these deficits. 462 genes in adult dorsal hippocampus
      from mice exposed to nicotine as adolescents showed altered promoter methylation
      that was reversed by choline supplementation. Gene network analysis revealed that
      chromatin remodeling genes were the most enriched category whose methylation was
      altered by nicotine and reversed by choline dietary supplementation. Two key
      chromatin remodeling genes, Smarca2 and Bahcc1, exhibited inversely correlated
      changes in methylation and expression due to nicotine exposure; this was reversed
      by choline. Our findings support a role for epigenetic modification of
      hippocampal chromatin remodeling genes in long-term learning deficits induced by
      adolescent nicotine and their amelioration by dietary choline supplementation.

PMID- 30099203
TI  - A contemporary study of mortality in the multiple sclerosis population of south
      east Wales.
AB  - BACKGROUND: Mortality studies in multiple sclerosis (MS) are valuable to identify
      changing disease patterns and inform clinical management. This study examines
      mortality in a British MS cohort. METHODS: Patients were selected from the
      southeast Wales MS registry. Hazard of death was analysed using Cox proportional
      hazards regression, adjusted for onset age, annualised relapse rate, initial
      disease course, time to EDSS 4.0, sex, socioeconomic status, and onset year. Age-
      and sex-stratified standardised mortality ratios (SMRs) were calculated by EDSS
      scores. RESULTS: Median time from MS diagnosis to death was 35.5 years and median
      age 73.9. Older onset age (hazard ratio [HR] 1.05, 95% confidence interval 1.03
      1.06) was associated with increased hazard of death. Primary progressive course
      was associated with increased hazard of death in women (HR 2.04, 1.15-3.63) but
      not men (HR 1.23, 0.61-2.47). Slow time to EDSS 4.0 (HR 0.41, 0.28-0.60) and high
      socioeconomic status (HR 0.54, 0.37-0.79) were associated with reduced hazard of
      death. SMR increased from EDSS 6.0 (3.86, 2.63-5.47) but more substantially at
      EDSS 8.0 (22.17, 18.20-26.75). CONCLUSIONS: Risk of death in MS varies
      substantially with degree of disability. This has important implications for
      clinical management and health economic modelling.

PMID- 30099205
TI  - Lower extremity deep venous thrombosis in a multiple sclerosis patient on
      dimethyl fumarate.

PMID- 30099204
TI  - No C9orf72 repeat expansion in patients with primary progressive multiple
      sclerosis.
AB  - Pathological repeat expansion (RE) of the C9orf72 hexanucleotide sequence is
      associated to amyotrophic lateral sclerosis (ALS) and frontotemporal dementia
      disease continuum, although other heterogeneous clinical phenotypes have been
      documented. The occurrence of multiple sclerosis (MS) in some C9orf72 carriers
      with a more severe ALS disease course has suggested a possible modifying role for
      MS. However, C9orf72 RE seems not to play a role in MS pathogenesis. In this
      study, we screened C9orf72 in 189 Italian patients with primary progressive MS
      (PPMS), a rare clinical form characterized by less inflammation over
      neurodegenerative features. We failed to detect C9orf72 RE, but a significant
      representation of intermediate alleles (>= 20 units) was observed in our PPMS
      cohort (2.1%) compared to healthy controls (0%, p < 0.05). In the normal range,
      allele distribution showed a trimodal pattern (2,5,8-repeat units) in PPMS and
      healthy controls with no significant difference. Our findings further demonstrate
      that C9orf72 RE is not genetically associated to MS spectrum, but suggest that
      intermediate alleles may represent risk factors as already reported for Parkinson
      disease.

PMID- 30099206
TI  - Epstein Barr virus shedding in multiple sclerosis: Similar frequencies of EBV in
      saliva across separate patient cohorts.
AB  - BACKGROUND: Epstein Barr Virus (EBV) infection is closely associated with
      multiple sclerosis (MS), but the relationship between viral load and disease
      activity is unclear. This study tested the observed levels of salivary EBV in MS,
      as a first step in investigating this relationship. METHODS: Real-time
      quantitative PCR (qPCR) was used to measure EBV DNA levels in saliva samples from
      three separate Multiple Sclerosis (MS) patient cohorts. RESULTS: The qPCR assay
      was used to delineate EBV shedding, defined here as a reliably detectable level
      of extracellular EBV DNA in saliva. Frequency of EBV shedding was found to be
      similar across the groups, with 20-25% of subjects releasing virus on any given
      sampling date. Diurnal variation in EBV count was tested in one of the cohorts,
      in which 26% of subjects showed more than a 10-fold difference between the
      highest and lowest EBV levels on a single day. In the same cohort, elevated viral
      levels at one time point did not predict elevated viral levels at a subsequent
      time point. CONCLUSIONS: These results indicate that EBV lytic activity in a
      subject cannot be inferred from a single measure of EBV in saliva. Also, subjects
      do not appear to be behave constantly as "EBV shedders" or "non-shedders". The
      assay is useful in giving a clear indication of salivary gland EBV lytic activity
      across a patient cohort - for example, in testing anti-viral drugs in MS.

PMID- 30099207
TI  - Interleukin (IL)-8 polymorphisms contribute in suicide behavior.
AB  - Previous studies have highlighted the role of immune dysregulation in suicide
      behavior. Interleukin (IL)-8 is a chemokine with neuroprotective effects whose
      lower serum concentrations have been detected in individuals committed suicide.
      In the present study, we genotyped three single nucleotide polymorphisms (SNPs)
      within IL-8 gene (rs4073, rs2227306 and rs1126647) in 229 individuals who
      attempted suicide with soft suicide methods, 235 suicide victims and 290
      individuals without any history of psychiatric disorders or suicide attempt. The
      T allele of rs4073 was significantly over-represented in suicide attempt group
      compared with both control and completed suicide groups (adjusted P values of
      8.3E-7 and 9.8E-8 respectively). This SNP was associated with suicide attempt in
      both dominant and co-dominant models (P values of 6.2E-9 and 4.3 E-8
      respectively). The genotype and allele frequencies of other SNPs were not
      significantly different among the three study groups. The T C A haplotype
      (rs4073, rs2227306 and rs1126647 respectively) were significantly less prevalent
      in completed suicide group compared with suicide attempt group (OR (95% CI) =
      0.63 (0.46-0.86), adjusted P value = 0.03). Besides, the A T A haplotype has
      significant lower frequency in individuals who attempted soft suicide compared
      with controls (OR (95% CI) = 0.44 (0.26-0.75), adjusted P value = 0.02). However,
      this haplotype was significantly more prevalent in individuals attempted hard
      methods compared with those attempted soft methods (OR (95% CI) = 2.21 (1.26
      3.87), adjusted P value = 0.04). The present study provided further evidence for
      the role of IL-8 in suicide behavior.

PMID- 30099208
TI  - Attachment and psychotherapy.
AB  - Attachment theory provides a model for understanding (1) development within the
      context of the child's primary, and formative relationships, and (2) an adult's
      orientation toward lifelong intimate connections, social relationships, and
      autonomous exploration. Psychotherapy researchers have linked measures of patient
      attachment with therapeutic alliance, process, and outcomes. Studies of ruptures
      and discourse analysis distinguish in-session behaviors associated with different
      patterns of insecure attachments, and identify distinct ways of working with
      them. The therapist's own attachment organization and mentalizing capacity also
      play a significant role in therapeutic success. The key tenets of attachment
      informed psychotherapy are: (1) the therapist-patient attachment relationship is
      central to promoting change, (2) the in vivo recognition of attachment dynamics
      during therapy guides formulation and intervention, and (3) therapy can reshape
      attachment dynamics.

PMID- 30099210
TI  - Measurement Properties of Visual Analogue Scale, Numeric Rating Scale, and Pain
      Severity Subscale of the Brief Pain Inventory in Patients With Low Back Pain: A
      Systematic Review.
AB  - : The Visual Analogue Scale (VAS), Numeric Rating Scale (NRS), and Pain Severity
      subscale of the Brief Pain Inventory (BPI-PS) are the most frequently used
      instruments to measure pain intensity in low back pain. However, their
      measurement properties in this population have not been reviewed systematically.
      The goal of this study was to provide such systematic evidence synthesis. Six
      electronic sources (MEDLINE, EMBASE, CINAHL, PsycINFO, SportDiscus, Google
      Scholar) were searched (July 2017). Studies assessing any measurement property in
      patients with nonspecific low back pain were included. Two reviewers
      independently screened articles and assessed risk of bias using the COSMIN
      checklist. For each measurement property, evidence quality was rated as high,
      moderate, low, or very low (GRADE approach) and results were classified as
      sufficient, insufficient, or inconsistent. Ten studies assessed the VAS, 13 the
      NRS, 4 the BPI-PS. The 3 instruments displayed low or very low quality evidence
      for content validity. High-quality evidence was only available for NRS
      insufficient measurement error. Moderate evidence was available for NRS
      inconsistent responsiveness, BPI-PS sufficient structural validity and internal
      consistency, and BPI-PS inconsistent construct validity. All VAS measurement
      properties were underpinned by no, low, or very low quality evidence; likewise,
      the other measurement properties of NRS and BPI-PS. PERSPECTIVES: Despite their
      broad use, there is no evidence clearly suggesting that one among VAS, NRS, and
      BPI-PS has superior measurement properties in low back pain. Future adequate
      quality head-to-head comparisons are needed and priority should be given to
      assessing content validity, test-retest reliability, measurement error, and
      responsiveness.

PMID- 30099209
TI  - The Pain Course: 12- and 24-Month Outcomes From a Randomized Controlled Trial of
      an Internet-Delivered Pain Management Program Provided With Different Levels of
      Clinician Support.
AB  - Little is known about the long-term outcomes of emerging Internet-delivered pain
      management programs. The current study reports the 12- and 24-month follow-up
      data from a randomized controlled trial (n = 490) of an Internet-delivered pain
      management program, the Pain Course. The initial results of the trial to the 3
      month follow-up have been reported elsewhere. There were significant improvements
      in disability, depression, anxiety, and pain levels across 3 treatment groups
      receiving different levels of clinician support compared with a treatment as the
      usual control. No marked or significant differences were found between the
      treatment groups either after treatment or at the 3-month follow-up. The current
      study obtained long-term follow-up data from 78% and 79% of participants (n =
      397) at the 12-month and 24-month follow-up marks, respectively. Clinically
      significant decreases (average percent reduction; Cohen's d effect sizes) were
      maintained at the 12- and 24-month follow-ups for disability (average reduction
      >=27%; d >= .67), depression (average reduction >=36%; d >= .80), anxiety
      (average reduction >=38%; d >= .66), and average pain levels (average reduction
      >=21%; d >= .67). No marked or consistent differences were found among the 3
      treatment groups. These findings suggest that the outcomes of Internet-delivered
      programs may be maintained over the long term. PERSPECTIVE: This article presents
      the long-term outcome data of an established Internet-delivered pain management
      program for adults with chronic pain. The clinical improvements observed during
      the program were found to be maintained at the 12- and 24-month follow-up marks.
      This finding indicates that these programs can have lasting clinical effects.

PMID- 30099211
TI  - Exploring the Relationships Between Altered Body Perception, Limb Position Sense,
      and Limb Movement Sense in Complex Regional Pain Syndrome.
AB  - : Chronic pain is often accompanied by patient-reported distorted body perception
      and an altered kinesthesia (referring to the senses of limb position and limb
      movement), but the association between these deficits is unknown. The objectives
      of this study were to assess body perception and the senses of limb position and
      limb movement in complex regional pain syndrome (CRPS) and to test whether these
      variables are related to each other and to pain intensity. Thirteen patients with
      upper limb CRPS (mean pain intensity, 4.2 +/- 2.4 out of 10) and 13 controls were
      recruited. Body perception was self-reported with a questionnaire, and the senses
      of limb position (task 1) and of limb movement (task 2) were assessed with a
      robotic system combined with a 2D virtual reality display. The results showed
      altered kinesthesia in the patients with CRPS compared with controls (all P <
      .05). Moreover, in the CRPS group, greater pain intensity was associated with
      lower performance on task 2 (r = -.60; P < .05). Although alterations in
      participants' sense of limb position and limb movement were associated with each
      other (r = -.70, P < .01), they were not related to the altered body perception
      (all P > .26). Therefore, the results suggest that kinesthesia and body
      perception should be considered and evaluated separately in patients with CRPS.
      PERSPECTIVE: Senses of limb position and movement rely on sensorimotor
      integration. Both are altered in complex regional pain syndrome. However, they
      are not related to the subjective perception of the painful limb, and thus they
      should be assessed separately in rehabilitation.

PMID- 30099212
TI  - NLC versus nanoemulsions: Effect on physiological skin parameters during regular
      in vivo application and impact on drug penetration.
AB  - Nanostructured lipid carriers (NLC) and nano-sized emulsions based on monoacyl
      phosphatidylcholine (MAPL) were tested for their effect on physiological skin
      parameters in vivo during daily application over four weeks. The influence of the
      basic formulations on transepidermal water loss (TEWL), skin hydration, sebum
      content and pH was determined once per week and after a recovery period of three
      weeks. In addition, confocal Raman spectroscopy was employed to evaluate natural
      moisturising factor and urea content. The results showed that the tested NLC
      systems with different MAPL content led to increased TEWL and decreased stratum
      corneum hydration, NMF and urea content. This effect was more pronounced for NLC
      with higher MAPL content and less pronounced for corresponding emulsions with
      increased oil phase volume. The observed effects indicate temporarily impaired
      barrier function; however, all effects were reversible after the treatment was
      finished. Additional tape stripping penetration experiments were performed on
      intact human forearm skin in vivo using the model substance curcumin. Higher
      total penetrated curcumin amounts were found for NLC-based formulations when
      compared to the emulsion. Comparative in vitro tape stripping data on porcine ear
      skin confirmed the trends observed in vivo. In summary, these findings suggest
      that the effect of the developed MAPL-based NLC and nano-sized emulsion on skin
      barrier function differs mildly in a one-time application setup, but may increase
      strongly during daily application over a longer treatment period.

PMID- 30099213
TI  - Novel approaches for improving stability of cysteamine formulations.
AB  - Cystinosis is a genetic disorder that leads to the formation of cystine crystals
      in many organs in the body including cornea. Ocular manifestation of this disease
      is treated by eye drops of cysteamine which can easily oxidize into its disulfide
      cystamine. The rapid oxidation limits the shelf life as well the duration during
      which the drug can be used after opening the eye drop bottle. We evaluate two
      approaches of preventing the oxidation of cysteamine with the goal of increasing
      the time of use after opening the bottle to one month. The first approach
      integrates antioxidants such as catalase enzyme and vitamins C and E into the
      aqueous solution. Results show that catalase is the most effective additive as it
      decreases the oxidation rate by 58%, which on its own is not sufficient to reach
      targeted one month stability. The second approach focuses on incorporating
      diffusion barriers to prevent oxygen from reaching the cysteamine solution. This
      was accomplished by two methods: formulation of a hydrophobic layer which floats
      on the surface of the aqueous solution and integration of OMAC(r) oxygen
      resistant material into the eye drop bottle. Both methods delay the onset of
      cysteamine degradation and decrease the rate of degradation. In particular, an
      eye drop bottle with three layers of OMAC(r) has less than 10% degradation after
      one month of opening the bottle and withdrawing a drop each day. By integrating
      all three methods, we designed a system where >90% of cysteamine remains in the
      active form for 70 days after opening the bottle. In addition, we examine the use
      of OMAC(r) as heat-sealed pouches for storage of cysteamine eye drop bottles
      during packaging to eliminate the need for the current approach of freezing the
      formulation during shipping. The results show that such heat-sealed pouches would
      keep cysteamine stable for over one year at ambient conditions.

PMID- 30099214
TI  - Redox sensitive lipid-camptothecin conjugate encapsulated solid lipid
      nanoparticles for oral delivery.
AB  - Camptothecin (CPT) is an important topoisomerase I enzyme (Topo I) targeting anti
      cancer drug, but its oral administration is limited by poor bioavailability and
      severe side effects. In this study, a redox sensitive CPT prodrug loaded solid
      lipid nanoparticles (SLN) system for oral delivery was developed. First of all,
      CPT-palmitic acid conjugate via a cleavable disulfide bond linker (CPT-SS-PA) was
      synthesized and encapsulated into SLN. The drug release of SLN was evaluated in
      neutral environment, simulated gastrointestinal fluid and reductive solution. The
      results indicated that CPT-SS-PA SLN maintained chemical structural stability in
      simulated physiological environment but exhibited quick reduction-response
      release of CPT in the presence of dithiothreitol. Furthermore, in vitro
      cytotoxicity of CPT-SS-PA SLN was tested against cancer cell lines, and the
      cellular uptake behavior for oral delivery was checked by confocal laser scanning
      microscopy (CLSM) using Caco-2 cells model. From the data, CPT-SS-PA SLN revealed
      high anti-cancer activity and enhanced Caco-2 cell absorption. Finally, the oral
      bioavailability and intestinal safety of CPT-SS-PA SLN were preliminary evaluated
      by in vivo pharmacokinetic and histopathological study, respectively. This study
      demonstrated that CPT-SS-PA SLN could be developed as an effective CPT oral
      delivery system due to its enhanced oral bioavailability and reduced intestinal
      side effect.

PMID- 30099215
TI  - Electrospun fixed dose formulations of amlodipine besylate and valsartan.
AB  - Increasing numbers of elderly people require multi-drug therapies. One route to
      improve adherence rates is to prepare fixed dose combinations (FDCs), in which
      multiple active ingredients are loaded into a single formulation. Here, we report
      the use of electrospinning to prepare fast-dissolving oral FDCs containing
      amlodipine besylate and valsartan, two drugs prescribed as FDCs for the treatment
      of hypertension. Electrospun fibers were prepared loaded with one or both drugs,
      using polyvinylpyrrolidone as the polymer matrix. The fibers were largely
      cylindrical in morphology and comprise amorphous solid dispersions except with
      the highest loadings of amlodipine besylate. HPLC demonstrated drug entrapment
      efficiencies of >85% of the theoretical dose. The mats have folding endurances
      and thicknesses suitable for use as oral films. The amlodipine besylate-loaded
      systems are fast-dissolving, with >90% release obtained within 120 s. In
      contrast, valsartan release from its single-drug formulations took longer,
      ranging from 360 s to 24 min. With the FDC formulations, rapid release within 360
      s was achieved when the loading was 5% w/w of each drug, but again the release
      time increased with drug loading. Electrospun fibers therefore have significant
      promise as FDCs, but the target drug and its loading need to be carefully
      considered.

PMID- 30099216
TI  - An attempt to study (111) oriented NiO-like TCO thin films in terms of
      structural, optical properties and photocatalytic activities under strontium
      doping.
AB  - This work covers some physical properties of Sr-doped NiO sprayed thin films at
      various concentrations (0 to 4%) prepared on glass substrates. Structural
      properties by using X-ray diffraction (XRD) show that all films have a cubic
      structure with (111) orientation. The stress, estimated by adjusting the XRD
      diffraction peaks increases with the doping concentration. Also, the grain size
      decreases with the doping concentration. On the other hand, the stacking fault
      probability has been discussed in terms of Sr doping level. The surface
      morphology of NiO:Sr thin films were examined by AFM observations. The optical
      constants (refractive index and extinction coefficient) were obtained by
      reflectance and transmittance measurements. This optical measurements show that
      the optical band gap is around 3.8 eV. PL measurements show mainly the transition
      band in UV blue and green domains related to the band-to-band transition and some
      defects in these prepared thin films. Finally, the advances in the actively
      studied photocatalysts that are emerging as effective alternate for nickel oxide
      based photocatalysts is also discussed.

PMID- 30099217
TI  - Paying more for less? Insurer competition and health plan generosity in the
      Medicare Advantage program.
AB  - This paper explores the relationship between insurer competition and health plan
      benefit generosity by examining the impact of a regulatory change that caused the
      cancellation of 40% of the private plans in Medicare. I isolate cancellation's
      causal effect by using variation induced by insurers canceling all plans
      nationally. Results show that insurers in markets affected by cancellation
      reduced the benefit generosity of the plans remaining in the market. In the
      average market, out-of-pocket costs for a representative beneficiary enrolled in
      plans not directly affected by the policy increased by $91 annually. In the least
      competitive markets, out-of-pocket costs increased by roughly $64-$127 a year for
      enrollees in those plans. Meanwhile in the most competitive markets, benefit
      generosity barely changed. These findings have crucial implications for markets
      such as health insurance exchanges, as they suggest that plan generosity is
      degraded when competition declines.

PMID- 30099218
TI  - Deriving risk adjustment payment weights to maximize efficiency of health
      insurance markets.
AB  - Risk-adjustment is critical to the functioning of regulated health insurance
      markets. To date, estimation and evaluation of a risk-adjustment model has been
      based on statistical rather than economic objective functions. We develop a
      framework where the objective of risk-adjustment is to minimize the efficiency
      loss from service-level distortions due to adverse selection, and we use the
      framework to develop a welfare-grounded method for estimating risk-adjustment
      weights. We show that when the number of risk adjustor variables exceeds the
      number of decisions plans make about service allocations, incentives for service
      level distortion can always be eliminated via a constrained least-squares
      regression. When the number of plan service-level allocation decisions exceeds
      the number of risk-adjusters, the optimal weights can be found by an OLS
      regression on a straightforward transformation of the data. We illustrate this
      method with the data used to estimate risk-adjustment payment weights in the
      Netherlands (N = 16.5 million).

PMID- 30099219
TI  - Killer-cell immunoglobulin-like receptors associated with polycystic ovary
      syndrome.
AB  - : Polycystic ovary syndrome (PCOS) affects the endocrine system and is associated
      with low-grade inflammation. Natural killer (NK) cells are involved in the
      defense of the female reproductive tract, folliculogenesis, ovulation and the
      menstrual cycle. The killer-cell immunoglobulin-like receptors (KIR) on the
      surface of NK cells modulate the activation and function of these cells after
      interacting with human leukocyte antigen (HLA) class I ligands. The objective of
      this study was to evaluate the possible association of the KIR and their HLA
      ligands with polycystic ovary syndrome. METHODS: Ninety-three patients with PCOS
      according to the Rotterdam criteria and 104 healthy controls were included in
      this study. The HLA class I and KIR genotypes were determined using a PCR-SSO
      technique, rSSO Luminex(r). In order to assess whether the distribution of the
      HLA and KIR genotypes was in Hardy-Weinberg equilibrium, Arlequin 3.1 software
      was used. The frequency distributions in the two study groups were compared using
      the chi-squared statistic with Yates's correction using Open Epi software.
      RESULTS: The higher frequencies of KIR3DS1-Bw4 (41% vs. 19%, Pc = 0.002; OR =
      2.90) and homozygotic KIR2DS4-del (54% vs. 26%, Pc = 0.0002; OR = 3.316) in
      patients compared with controls suggest they confer susceptibility to PCOS. A
      lower frequency of KIR2DS4-full was observed in patients (43% vs. 70%, Pc =
      0.0004, OR = 0.320). CONCLUSION: KIR and its HLA ligands were associated with the
      development of PCOS in the studied population.

PMID- 30099220
TI  - Local and systemic levels of cytokines and danger signals in endometriosis
      affected women.
AB  - Endometriosis is a prevalent gynaecological disorder with a still unclear
      pathogenesis. So far inflammatory mechanisms are associated with disease
      progression and critical reviews have discussed the so-called 'danger theory'
      related to endometriosis. Hence, we performed immunoassays to evaluate whether
      local inflammation is linked to the severity of the disease. In addition, we
      investigated the role of recently described cytokines IL-33, IL-32alpha and the
      'alarmin' high mobility group box 1 (HMGB1). We confirmed a dysfunctional immune
      response in the local environment of women suffering from endometriosis. However,
      we found no direct evidence for a significant up-regulation of danger signals in
      endometriosis, irrespective of the severity of the disease.

PMID- 30099221
TI  - Three-dimensional pharyngeal airway changes in dento-skeletal class II patients
      after two-jaw orthognathic surgery with segmentation - a pilot study.
AB  - PURPOSE: To investigate short- and long-term post-surgical three-dimensional
      changes of pharyngeal airway morphology and hyoid bone position in dento-skeletal
      class II deformity patients after two-jaw surgery with segmentation. METHODS:
      Relations between skeletal movement, hyoid bone position and three-dimensional
      pharyngeal airway changes were retrospectively analyzed on pre- and post-surgical
      CBCTs in dento-skeletal class II patients who underwent orthognathic two-jaw
      surgery with segmentation. RESULTS: While long-term significant reductions in
      length (P= 0.003), surface area (P= 0.042) and volume (P= 0.004) were found in
      the nasopharynx, the highly significant increases in oropharyngeal airway length,
      surface area, volume and the minimal cross-sectional area (P < 0.05) prevailed
      only in the short-term. Although a significant antero-superior movement of the
      hyoid bone was detected both in short- and long-term follow-up CBCTs (P < 0.05),
      only its superior, but not the anterior movement was found to be associated with
      an increased lateral width of the oropharyngeal minimal cross-sectional area.
      CONCLUSION: Two-jaw orthognathic surgery with segmentations in dento-skeletal
      class II patients improved oropharyngeal airway parameters significantly in the
      short-, but not long-term.

PMID- 30099222
TI  - Metabolic features and regulation of the healing cycle-A new model for chronic
      disease pathogenesis and treatment.
AB  - Without healing, multicellular life on Earth would not exist. Without healing,
      one injury predisposes to another, leading to disability, chronic disease,
      accelerated aging, and death. Over 60% of adults and 30% of children and teens in
      the United States now live with a chronic illness. Advances in mass spectrometry
      and metabolomics have given scientists a new lens for studying health and
      disease. This study defines the healing cycle in metabolic terms and reframes the
      pathophysiology of chronic illness as the result of metabolic signaling
      abnormalities that block healing and cause the normal stages of the cell danger
      response (CDR) to persist abnormally. Once an injury occurs, active progress
      through the stages of healing is driven by sequential changes in cellular
      bioenergetics and the disposition of oxygen and carbon skeletons used for fuel,
      signaling, defense, repair, and recovery. >100 chronic illnesses can be organized
      into three persistent stages of the CDR. One hundred and two targetable
      chemosensory G-protein coupled and ionotropic receptors are presented that
      regulate the CDR and healing. Metabokines are signaling molecules derived from
      metabolism that regulate these receptors. Reframing the pathogenesis of chronic
      illness in this way, as a systems problem that maintains disease, rather than
      focusing on remote trigger(s) that caused the initial injury, permits new
      research to focus on novel signaling therapies to unblock the healing cycle, and
      restore health when other approaches have failed.

PMID- 30099223
TI  - Treatment and outcomes of patients in the Brain Metastases in Breast Cancer
      Network Registry.
AB  - BACKGROUND: Brain metastases (BMs) have a major impact on life expectancy and
      quality of life for many breast cancer patients. Knowledge about treatment
      patterns and outcomes is limited. METHODS: We analysed clinical data of 1712
      patients diagnosed with BMs from breast cancer between January 2000 and December
      2016 at 80 institutions. RESULTS: Median age at diagnosis of BMs was 56 years (22
      90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328)
      had triple-negative and 30.8% (n = 471) had hormone receptor (HR)-positive, HER2
      negative (luminal-like) primary tumours. The proportion of patients with HER2
      positive BMs decreased comparing the years 2000-2009 with 2010-2015 (51%-44%),
      whereas the percentage of patients with luminal-like tumours increased (28%-34%;
      p = 0.0331). Patients with BMs in the posterior fossa were more often HER2
      positive (n = 169/314, 53.8%) than those diagnosed with triple-negative (n =
      65/314, 20.7%) or luminal-like primary breast cancer (n = 80/314, 25.5%), (p <
      0.0001). Median overall survival (OS) time after development of BMs for the
      overall cohort was 7.4 months (95% confidence interval [CI]: 6.7-8.0 months). One
      year survival rate was 37.7% (95% CI: 35.2-40.1). Patients with HER2-positive
      tumours had the longest median OS of 11.6 months (95% CI: 10.0-13.4) compared
      with 5.9 months (95% CI: 5.0-7.2) for patients with luminal-like and 4.6 months
      (95% CI: 3.9-5.4) for patients with triple-negative tumours. Patients with HER2
      positive tumours who received anti-HER2 treatment had longer median OS than those
      without (17.1 months versus 7.2 months, p < 0.0001). CONCLUSIONS: Prognosis of
      patients after developing BMs varies significantly according to the subtype. The
      outcome in this cohort is similarly poor in triple-negative and HR-positive/HER2
      negative patients. Our results underline the high medical need for improvement of
      treatment and prevention strategies for BMs in breast cancer patients.

PMID- 30099224
TI  - Adiabatic and constant volume decomposition process of condensed phase delta
      1,3,5,7-tetranitro-1,3,5,7-tetrazocane at high temperatures: Quantum molecular
      dynamics simulations.
AB  - We performed quantum molecular dynamics simulations to investigate the initiation
      chemistry of condensed phase delta-HMX at high temperatures by maintaining
      constant energy and volume to model adiabatic initiation process. The
      decomposition of HMX began by the C-N bond breaking in one molecule and by the C
      H bond cleavage in other HMX molecule at 2400 K. At 2700 K, HMX is triggered by
      only one path that the C-N bond broke and the ring opened. At 3000 K, the
      decomposition of HMX is triggered by the C-H bond and N-O bond fission in the
      branch chains. There are seven decomposition channels observed during the whole
      decomposition stage. The N-O bond cleavage is a dominant reaction pathway. The
      boat configuration of the HMX molecule caused a new reaction channel to be
      happened by forming a new N-N bond. Another new reaction channel took place to
      form a new N-C bond due to intermolecular effects.

PMID- 30099225
TI  - Impact of uterine fibroids on quality of life: a national cross-sectional survey.
AB  - OBJECTIVE: To study clinical impact of symptomatic uterine fibroids on women's
      health-related perceived quality of life regarding several dimensions. STUDY
      DESIGN: A prospective cross-sectional web-based survey was conducted from August
      18th to September 2nd 2016 among the general French population of women. A total
      of 1287 French women over the age of 18, among which 302 reported symptomatic
      uterine fibroids were surveyed. Data concerning demographics, symptoms and health
      related quality of life (HRQL) using the UFS-QoL questionnaire, an overall well
      being score and overall discomfort score were collected. RESULTS: Almost two
      thirds of surveyed women (n = 193; 64%) reported moderate to severe fibroid
      related symptoms (symptom severity score between 40 and 100). The global HRQL
      score showed that 64% of women (n = 193) reported a moderate to very important
      impact of fibroids on quality of life (HRQL global score between 0 and 50). The
      worse HRQL scores were reported for concern (57.5 +/- 26.7), energy (58.1 +/-
      23.2) and self-conscious subscales (63.4 +/- 24.3). The mean overall well-being
      score was lower in women with symptomatic uterine fibroids (6.6 +/- 1.7) than in
      women without (7.3 +/- 1.5). The mean overall discomfort score rated by women
      with symptomatic uterine fibroid was 5.7 +/- 2.5 with a score between 6 and 10
      reported by 56% of them. CONCLUSIONS: We observed that 64% of surveyed women
      reported a moderate to very important impact of fibroids on their quality of
      life. This perceived alteration of quality of life together with the severity of
      symptomatic fibroids have a significant impact on the overall level of discomfort
      perceived by women and on their personal quality of life.

PMID- 30099226
TI  - Physical activity and body image dissatisfaction among pregnant women: A
      systematic review and meta-analysis of cohort studies.
AB  - Body image dissatisfaction has increased among pregnant women, affecting their
      mental and physical activities. Previous systematic reviews only found
      significant results existed in cross-sectional design instead of longitudinal
      designs. This meta-analytic review of cohort studies aimed to report the
      relationships and moderator variables about body image dissatisfaction and
      physical activity among pregnant women. We searched for studies in PubMed,
      EMBASE, Web of Science and the Cochrane library until December 2017. Cohort
      studies that were written in English and reported on the effect size between
      physical activity and body image dissatisfaction among pregnant women were
      eligible for inclusion. The authors evaluated the risk of bias in all eligible
      studies, extracted data, and used a random-effects model to assume the
      correlation and potential moderator variables. Ultimately, only 4 cohort studies
      met eligibility criteria. There was a total sample size (n) of 406 pregnant women
      and 8 individual effect sizes. The pregnant women who exercised a lot had better
      body image satisfaction (R=0.151, 95% confidence interval [CI], 0.078-0.223,
      Z=4.001, p=0.000, I2=23.052%). The moderator variables were the pregnancy time
      points and body mass index. The first meta-analysis evaluated the correlations
      and moderator variables of physical activity and body image dissatisfaction in
      pregnancy. More and high-quality, randomized clinical trials are needed in future
      research.

PMID- 30099228
TI  - Parents' perception of child behavior, parenting stress, and child abuse
      potential: Individual and partner influences.
AB  - Based on the Social Information Processing model of parenting risk for child
      abuse, the present study examined the associations between mothers' and fathers'
      perception of child behavior and child abuse potential, as well as whether
      parenting stress mediates the association between these constructs. Two hundred
      and fifty-nine mother-father couples raising preschool children answered the
      Child Behavior Checklist (CBCL), the Parenting Stress Index (PSI), and the Child
      Abuse Potential Inventory (CAPI). The results of dyadic path analysis showed that
      perception of child behavior was related to heightened parenting stress and abuse
      potential in both mothers and fathers. Concerning partner effects, we found that
      mothers' perception of child behavior problems was positively associated with
      fathers' parenting stress and that the higher the mothers' distress, the higher
      the fathers' risk of physical abuse. Finally, parenting distress partially
      mediated the association between parents' perception of child behavior and child
      abuse potential, with mothers' perception of their children as problematic
      showing a significant indirect effect through distress on their own abuse risk
      and on fathers' CAP as well. These findings suggest that parental distress may
      represent a critical mechanism by which parents' negative views of their children
      contribute to abuse potential. Moreover, mothers seem to influence fathers'
      tendency towards abusive behaviors.

PMID- 30099229
TI  - Age-specific risk factors associated with placement instability among foster
      children.
AB  - Placement instability places foster children at an increased risk of negative
      developmental outcomes. Previous research has yielded inconsistent results on
      risk factors for placement instability. Therefore, we investigated two research
      questions: (1) Which child attributes and case histories are associated with
      placement disruptions (moves indicative of child, agency or caregiver
      dissatisfaction with the existing placement)?; and (2) How do associations of
      child attributes and case histories with placement disruptions vary by
      developmental stage --early childhood (0-5 years), middle childhood (6-12 years),
      and adolescence (13 years or older)? Using a complete entry cohort of 23,765
      foster children in Texas, our results demonstrated that the effects of different
      risk factors varied by placement end reason and across developmental stages. Of
      note, kinship placement, compared to non-relative foster care, and placement with
      all siblings were each associated with an increased risk of substandard care
      disruptions. Placements with females or Hispanic children were at an increased
      risk of child-initiated disruption, whereas placements with Black children were
      more likely to end due to placement mismatch or substandard care reasons.
      Finally, the adolescence age group was always associated with the greatest
      increase in risk regardless of disruption reason. These findings provide
      researchers, caseworkers, and policymakers important information on the risk
      factors for placement instability among children in foster care.

PMID- 30099227
TI  - SAMHD1 deficient human monocytes autonomously trigger type I interferon.
AB  - Germline mutations in the human SAMHD1 gene cause the development of Aicardi
      Goutieres Syndrome (AGS), with a dominant feature being increased systemic type I
      interferon(IFN) production. Here we tested the state of type I IFN induction and
      response to, in SAMHD1 knockout (KO) human monocytic cells. SAMHD1 KO cells
      exhibited spontaneous transcription and translation of IFN-beta and subsequent
      interferon-stimulated genes (ISGs) as compared to parental wild-type cells. This
      elevation of IFN-beta and ISGs was abrogated via inhibition of the TBK1-IRF3
      pathway in the SAMHD1 KO cells. In agreement, we found that SAMHD1 KO cells
      present high levels of phosphorylated TBK1 when compared to control cells.
      Moreover, addition of blocking antibody against type I IFN also reversed
      elevation of ISGs. These experiments suggested that SAMHD1 KO cells are
      persistently auto-stimulating the TBK1-IRF3 pathway, leading to an enhanced
      production of type I IFN and subsequent self-induction of ISGs.

PMID- 30099230
TI  - Incorporation of Black Soldier Fly (Hermetia illucens L.) larvae fat or extruded
      linseed in diets of growing rabbits and their effects on meat quality traits
      including detailed fatty acid composition.
AB  - The inclusion of Black Soldier Fly (BSF) fat or extruded linseed (LIN) in diets
      for growing rabbits on meat fatty acids (FA), dimethyl acetals (DMA), oxidative
      stability and color was evaluated. Forty-eight rabbits with 35 days of age were
      individually housed, fed one of 4 diets (LIN-Low, 30 g/kg of fat from LIN; LIN
      High, 60 g/kg of fat from LIN; BSF-Low, 30 g/kg of BSF fat; BSF-High, 60 g/kg of
      BSF fat) and slaughtered after 5 weeks. Diets with BSF reduced the intramuscular
      FA but increased the 12:0 and 14:0 in meat compared to LIN, whereas LIN diets
      increased the 18:3n-3 deposition in meat. Regressions between FA intake and FA
      meat concentration indicate that the deposition of 12:0 and 14:0 in the meat of
      BSF-fed rabbits was lower than the deposition of n-3 PUFA in the meat of LIN-fed
      rabbits. Overall, lipid profiles of meat from BSF-fed rabbits were less healthy,
      but meat from LIN-fed rabbits was the more susceptible to oxidation.

PMID- 30099231
TI  - Predicting pork freshness using multi-index statistical information fusion method
      based on near infrared spectroscopy.
AB  - In this work, the near infrared spectroscopy (NIR) technology was applied to
      nondestructively evaluate the freshness of pork. The total volatile basic
      nitrogen (TVB-N) and pH value of pork were detected as freshness evaluation
      indicators. A multi-index statistical information fusion (MSIF) modeling method
      based on variable selection was proposed to evaluate pork freshness. In the
      experiment, the proposed MSIF was compared with other state-of-the-art variable
      selection methods. Results showed that the proposed method achieved the best
      generalization performance and stability. The prediction correlation coefficient
      (Rval) and root mean square error (RMSEP) of MSIF were: Rval = 0.8618 and RMSEP =
      3.910 for TVB-N content, Rval = 0.9379 and RMSEP = 0.1046 for pH value. The
      research demonstrated that NIR combined with MSIF has the potential for rapid and
      nondestructive determination of pork freshness, and so hopefully to provide a
      promising tool for monitoring meat quality and enriching the extracted
      information from food industry.

PMID- 30099232
TI  - Assessment of the energy expenditure of Belgian nursing home residents using
      indirect calorimetry.
AB  - OBJECTIVES: The aim of this study was to assess the energy expenditure of Belgian
      nursing home residents using indirect calorimetry and compare the energy
      expenditure with energy intake. METHODS: Indirect calorimetry was performed in
      nursing home residents to estimate their basal metabolism. The basal metabolism
      was multiplied by a physical activity level coefficient and energy expenditure
      that was related to thermogenesis (i.e., 10% of the total amount of energy
      ingested over 24 h) was added. In this way, we obtained the total energy
      expenditure of each nursing home resident. The nutritional intake of each
      resident was calculated using the precise food-weighing method over a 3-d period.
      The difference between energy expenditure and consumption was calculated for each
      patient and the mean of the difference in the population was calculated. These
      quantitative variables were compared by means of analysis of variance. RESULTS: A
      total of 25 subjects were included in this study (88.1 +/- 5.8 y; 84% women). The
      estimated mean basal metabolism was 1087.2 +/- 163.2 kcal. The physical activity
      level was 1.29 +/- 0.1 on average and the energy expenditure due to thermogenesis
      was 163.1 +/- 28.9 kcal. Thus, the mean daily energy expenditure was 1575.2 +/-
      210.6 kcal, which was within the range of the actual calculated energy intake of
      the residents (1631.5 +/- 289.3 kcal; P = 0.33). CONCLUSIONS: The estimated
      energy intake of Belgian nursing home residents seems appropriate for their
      energy expenditure.

PMID- 30099233
TI  - A versatile cathodic "signal-on" photoelectrochemical platform based on a dual
      signal amplification strategy.
AB  - Novel cathodic photoelectrochemical (PEC) aptasensors for sensitive and selective
      determination of thrombin and Pb2+ were developed based on a new dual-signal
      amplification strategy. The presence of gold nanoparticles (AuNPs) could quench
      the PEC signal of bismuth oxyiodide (BiOI). At the same time, the redox moiety G
      quadruplex/hemin or ferrocene (Fc) was found to enhance the PEC signal of BiOI.
      So, in the presence of thrombin or Pb2+, the interaction between target and the
      aptamer resulted in the releasement of the AuNPs, as well as shorter distance
      between the redox moiety and the electrode surface. Hence dual-enhanced cathodic
      PEC biosensor strategy was realized. Under the optimized conditions, the
      detection limits of thrombin and Pb2+ were 17.3 fM and 3.16 pM, respectively with
      good selectivity. At the same time, the PEC performance of redox moiety G
      quadruplex/hemin and Fc was compared.

PMID- 30099235
TI  - Evaluation of long-term antiepileptic drug use in patients with temporal lobe
      epilepsy: Assessment of risk factors for drug resistance and polypharmacy.
AB  - PURPOSE: To evaluate risk factors for drug resistance and polypharmacy in
      patients with temporal lobe epilepsy. METHODS: Patients with temporal lobe
      epilepsy, treated for more than 5 years, completed questionnaires on
      antiepileptic drug use and effect. Logistic regression models were used for
      analysis of risk factors. RESULTS: Of 135 patients included in the study, 65%
      were classified as drug resistant and 41% identified as using polypharmacy. Poor
      effects associated with first-choice antiepileptic drug were reported by 59% of
      the patients, and 70% reported poor effects of second-line treatment. The most
      frequently used first-generation antiepileptic drugs had a similar mean effect to
      those of second-generation. Univariate regression analyses showed a significant
      association between drug resistance and mesial temporal sclerosis, seizure onset
      below 18 years, and lack of family history of epilepsy. However, multivariate
      regression analysis showed no association with any demographic or clinical
      features. Unsuccessful treatment with the first antiepileptic drug increased the
      risk of drug resistance by 18 times, and the risk of poor effect from the second
      antiepileptic drug by 9 times. Disease duration was associated with annual risk
      for drug resistance of 7% and for polypharmacy of 5%. CONCLUSIONS: A poor effect
      from initial pharmacotherapy is the only early risk factor for drug resistance
      found in this study. Long disease duration increases the risk of drug resistance
      and polypharmacy. Second-generation antiepileptic drugs provide no additional
      effect for poor responders to first-generation drugs.

PMID- 30099236
TI  - Changes to sleep-wake behaviors are associated with trajectories of pubertal
      timing and tempo of secondary sex characteristics.
AB  - We examined relations between sleep-wake behaviors and pubertal development from
      age 8.5 through 15.5 years in a US-based sample of 488 boys (75% White) and 478
      girls (78% White). Applying conditional nonlinear growth models to 7-waves of
      longitudinal data, we examined how sleep-wake behaviors are related to individual
      differences in the developmental timing and tempo of secondary sex
      characteristics. For girls, results supported the hypothesis that circadian
      changes in bedtimes, wake times, sleep duration, and eveningness preference were
      uniquely related to development of discrete aspects of secondary sex
      characteristics. For boys, the hypothesis was generally not supported. Different
      endocrine systems related to discrete secondary sex characteristics may be
      responsible for more relations between sleep and pubic hair development than for
      breast or genital development. Further research into associations between
      adrenarche and sleep during puberty may help researchers understand more about
      the origins and timing of adolescent sleep changes.

PMID- 30099237
TI  - New method for establishing a 3D subject-specific numerical electromagnetic model
      using hybrid imaging modalities.
AB  - Numerical electromagnetic models that can mimic the dielectric properties of
      human tissues have been widely used for dosimetry-related studies in bio
      electromagnetics, particularly for the calculation of electromagnetic field
      distribution inside the human body, which is subject specific. Reports indicated
      that considerable electromagnetic field variations may occur inside different
      human subjects even when existing differences in the geometrical dimensions of
      these subjects are minimal. Therefore, a subject-specific three-dimensional (3D)
      electromagnetic model is crucially required to calculate the electromagnetic
      field distribution accurately. However, the manner in which a precise subject
      specific 3D electromagnetic model is established has not been fully explored in
      the literature yet. In this study, a new method was proposed for the
      establishment of a subject-specific 3D electromagnetic model using hybrid imaging
      modalities, with computed tomography (CT) and magnetic resonance (MR) images as
      sources. The exemplary application was provided by using the established subject
      specific model to calculate the local specific absorption rates in MR imaging.
      Comparison studies indicated that detailed information was obtained using the
      proposed model.

PMID- 30099234
TI  - A non-synthetic approach to extending the lifetime of hyperpolarized molecules
      using D2O solvation.
AB  - Although dissolution dynamic nuclear polarization is a robust technique to
      significantly increase magnetic resonance signal, the short T1 relaxation time of
      most 13C-nuclei limits the timescale of hyperpolarized experiments. To address
      this issue, we have characterized a non-synthetic approach to extend the
      hyperpolarized lifetime of 13C-nuclei in close proximity to solvent-exchangeable
      protons. Protons exhibit stronger dipolar relaxation than deuterium, so
      dissolving these compounds in D2O to exchange labile protons with solvating
      deuterons results in longer-lived hyperpolarization of the 13C-nucleus 2-bonds
      away. 13C T1 and T2 times were longer in D2O versus H2O for all molecules in this
      study. This phenomenon can be utilized to improve hyperpolarized signal-to-noise
      ratio as a function of longer T1, and enhanced spectral and imaging resolution
      via longer T2.

PMID- 30099238
TI  - Exploiting the semantic graph for the representation and retrieval of medical
      documents.
AB  - OBJECTIVE: The objective of this study was to propose a graph-based semantic
      search approach by addressing the inherent complexity and ambiguity of medical
      terminology in queries and clinical text for enhanced medical information
      retrieval. METHODS: The supportive use of a medical domain ontology exploits the
      light-weight semantics discovered from queries and documents for enhanced
      document ranking. First, the implicit information regarding concepts and the
      relations between them is discovered in the documents and queries and is used to
      evaluate the relevance of the query-document; then, the semantic linkages between
      concepts distributed in target documents and reference documents are built and
      used to score the document's popularity; finally, the above two evaluations are
      integrated to produce the final ranking list for document ranking. RESULTS:
      Empirical experiments are conducted on two different datasets. The results
      demonstrate that the proposed graph-based approach significantly outperforms the
      baselines. For example, the average performance improvement on two datasets of
      the best variant of GSRM compared to the best baseline achieve 7.2% and 7.9% in
      terms of P@20 and NDCG@20, respectively, which illustrates the effectiveness of
      the proposed approach.

PMID- 30099239
TI  - Influence of aging-induced flow waveform variation on hemodynamics in aneurysms
      present at the internal carotid artery: A computational model-based study.
AB  - The variation of blood flow waveform in the internal carotid artery (ICA) with
      age is a well-documented hemodynamic phenomenon, but little is known about how
      such variation affects the characteristics of blood flow in aneurysms present in
      the region. In the study, hemodynamic simulations were conducted for 26 ICA
      aneurysms, with flow waveforms measured in the ICAs of young and older adults
      being used respectively to set the inflow boundary conditions. Obtained results
      showed that replacing the young-adult flow waveform with the older-adult one led
      to little changes (<10%) in simulated time-averaged wall shear stress (WSS),
      transient maximum WSS, relative residence time and trans-aneurysm pressure loss
      coefficient, but resulted in a marked increase (32.36 +/- 17.24%) in oscillatory
      shear index (OSI). Frequency-domain wave analysis revealed that the progressive
      enhancement of low-frequency harmonics dominated the observed flow waveform
      variation with age and was a major factor contributing to the increase in OSI.
      Cross-sectional comparisons among the aneurysms further revealed that the degree
      of increase in OSI correlated positively with some specific morphological
      features of aneurysm, such as aspect ratio and size ratio. In summary, the study
      demonstrates that the variation in flow waveform with age augments the
      oscillation of WSS in ICA aneurysms, which underlies the importance of setting
      patient-specific boundary conditions in hemodynamic studies on cerebral
      aneurysms, especially those involving long-term patient follow-up or cross
      sectional comparison among patients of different ages.

PMID- 30099240
TI  - In vitro effect of a resin infiltrant on different artificial caries-like enamel
      lesions.
AB  - OBJECTIVES: A resin infiltrant was employed for the treatment of active white
      spot lesions due to its ability to penetrate into the enamel pores and prevent
      the progression of the lesion. However, limited information is available about
      its mechanical effect on different artificial enamel lesions as well as on its
      resistance to further demineralization. Therefore, this study aimed to evaluate
      the effects of the Icon(r) infiltrant on different artificial caries-like enamel
      lesions and its resistance to new acid challenges. DESIGN: Artificial lesions
      were produced in bovine enamel using three different protocols
      (demineralization/remineralization cycling, DE-RE; 8% methylcellulose gel, MC;
      and methyl ethyl diphosphonate solution, MHDP; n = 13). The specimens were
      treated with Icon(r) and subjected to a new acid challenge using DE-RE cycling.
      The surface and cross-sectional hardness were evaluated in sound, demineralized,
      treated and further demineralized enamel areas. Data were statistically analyzed
      using ANOVA and Tukey's test (p < 0.05). RESULTS: All of the demineralizing
      protocols produced subsurface artificial caries lesions. The infiltrant was able
      to partially recover the surface hardness and prevent further surface hardness
      loss in enamel previously demineralized using the DE-RE and MHDP protocols. In
      regard to cross-sectional hardness, no positive effect was found. CONCLUSIONS:
      The effect of the infiltrant depends on the type of lesion created in vitro, and
      its action is limited to the lesion surface.

PMID- 30099241
TI  - Knee motion and muscle activation patterns are altered in hip osteoarthritis: The
      effect of severity on walking mechanics.
AB  - BACKGROUND: Knee function is impaired in individuals with moderate hip
      osteoarthritis. How this extends to those undergoing total hip arthroplasty is
      unknown despite the common requirement for knee arthroplasty in this population.
      The study purpose was to determine whether sagittal plane knee joint movements
      and quadriceps and hamstring activation patterns differ between individuals with
      either moderate or severe unilateral hip osteoarthritis, and between ipsilateral
      and contralateral knees. METHODS: 20 individuals with moderate osteoarthritis and
      20 with severe osteoarthritis were recruited. Sagittal knee motion and surface
      electromyograms from the hamstrings and quadriceps were collected during
      treadmill walking at a self-selected speed. Principal component analysis captured
      amplitude and temporal sagittal plane motion and EMG waveform features. Student's
      t-tests and Analysis of Variance determined between group differences and
      within/between group leg differences. FINDINGS: The severe groups' contralateral
      knee was in greater flexion at initial contact and demonstrated a movement
      profile of a longer stance phase (p < 0.001). The severe group had reduced
      sagittal plane knee motion (p < 0.0001); more so in the ipsilateral knee (p <
      0.0001). The severe group had greater hamstring (p = 0.009) and quadriceps
      activation (p < 0.001) overall, specifically mid-stance quadriceps bilaterally (p
      = 0.002). Ipsilateral sagittal plane knee motion was reduced in both groups.
      Compared with those with moderate osteoarthritis, individuals with severe
      osteoarthritis walk with reduced sagittal plane knee motion bilaterally,
      suggesting prolonged contralateral stance, and elevated mid-stance hamstring and
      quadriceps activation. INTERPRETATION: Altered kinematics and muscle activity
      could contribute to a greater mechanical demand on the contralateral knee in
      those with more severe hip osteoarthritis.

PMID- 30099242
TI  - Impact of multilevel joint contractures of the hips, knees and ankles on the Gait
      Profile score in children with cerebral palsy.
AB  - BACKGROUND: Children with cerebral palsy are at risk of developing muscle
      contractures, often contributing to pain, structural deformities and mobility
      limitations. With the increasing use of gait indices to summarise the findings of
      three dimensional gait analysis (3DGA), the purpose of this study is to determine
      whether there is a relationship between multilevel joint contractures and the
      Gait Profile Score in children with cerebral palsy. METHODS: The Gait Profile
      Score, calculated from 3D gait analysis, and passive range of motion, strength
      and spasticity of the hips, knees and ankles in the sagittal plane were measured
      in 145 children with cerebral palsy (mean age:11 years,4 months; SD:2 years,10
      months) (83 males) enrolled in the NSW Paediatric Gait Analysis Service Research
      Registry from 2011 to 2016. The relationships between these physical measures and
      the Gait Profile Score were explored using bivariate and multivariate
      correlations. FINDINGS: Reduced hip extension, knee extension and ankle
      dorsiflexion (knee extended) range of motion were correlated with a higher
      (worse) Gait Profile Score (r = -0.348 to -0.466, p < .001). Children with all
      joints contracted had a significantly higher Gait Profile Score (mean 17.5
      degrees , SD 6.2 degrees ) than those with no contractures (mean 11.0 degrees ,
      SD 2.3 degrees ) or ankle contractures only (mean 12.8 degrees , SD 5.1 degrees )
      (p < .05). Knee flexion weakness, reduced hip extension and ankle dorsiflexion
      (knee extended) range of motion predicted 47% of the Gait Profile Score.
      INTERPRETATION: The Gait Profile Score is a sensitive measure for demonstrating
      the relationship between multilevel sagittal plane joint contractures and
      kinematic gait. Clinically, this supports the use of the Gait Profile Score as a
      simplified measure to understand the contribution of contractures to functional
      gait limitations. Monitoring knee flexion strength, and hip extension and ankle
      dorsiflexion (knee extended) range of motion may assist clinicians in
      prioritising interventions to improve gait in this population.

PMID- 30099243
TI  - Psychological time and intertemporal preference.
AB  - Many decisions people make involve intertemporal tradeoffs between current and
      future costs and benefits. Because outcomes in such decisions are separated by
      time (i.e., delay), the perception of time should play an important role.
      Traditionally, researchers have treated time as objective information (i.e.,
      calendar time) and examined the effect of different delays on intertemporal
      preference. Recently, researchers have started to take into account the
      subjective nature of future time perception and to use psychological (subjective)
      time rather than objective calendar time as a focal explanatory variable for
      intertemporal preference. The subjective nature of future time perception and its
      impact on intertemporal preference has particular significance because it implies
      that one's impatience can be reduced by altering his or her time perception.

PMID- 30099244
TI  - The influence of age and time horizon perspective on consumer behavior.
AB  - Past research has highlighted the role of time horizon view (i.e. the perception
      of remaining time as either limited or expansive) in goal salience and goal
      pursuit. Past studies have consistently found that age is associated with an
      increased focus on emotion. The present article focuses on the perception that
      time is limited as a key reason for older (versus young) adults' increased focus
      on emotions. This article investigates some important effects of aging and time
      horizon view on consumers' goals and preferences using Socioemotional Selectivity
      Theory.

PMID- 30099245
TI  - Identification of mutations in the PARK2 gene in Serbian patients with
      Parkinson's disease.
AB  - Mutations in the PARK2 (PRKN) gene are the most common cause of autosomal
      recessive (AR) juvenile parkinsonism and young-onset Parkinson's disease (YOPD).
      >100 different variants have been reported, including point mutations, small
      indels and single or multiple exon copy number variations. Mutation screening of
      PARK2 was performed in 225 Serbian PD patients (143 males and 82 females) with
      disease onset before 50 years and/or positive family history with apparent AR
      inheritance. All coding regions and their flanking intronic sequences were
      amplified and directly sequenced. Whole exon multiplications or deletions were
      detected using Multiple Ligation Probe Amplification (MLPA) method. We identified
      12 PD patients with PARK2 mutations (5.3%). Five patients (2.2%) had biallelic
      mutations and seven (3.1%) were single mutation carriers. Patients with compound
      heterozygous mutations had earlier onset of the disease compared to non-carriers
      (p = 0.005) or heterozygotes (p = 0.001). Other clinical features in mutation
      carriers were not different compared to non-carriers. In our cohort, sequence and
      dosage variants were equally represented in patients, inducing their first
      symptoms mainly before the age of 30. For efficient genetic testing strategy,
      patients with early, especially juvenile onset of PD were strong candidates for
      both dosage and sequence variants screening of PARK2 gene.

PMID- 30099246
TI  - Rotigotine transdermal patch for the treatment of neuropsychiatric symptoms in
      Parkinson's disease: A meta-analysis of randomized placebo-controlled trials.
AB  - OBJECTIVE: To systematically evaluate and quantify the effects of rotigotine
      treatment on neuropsychiatric symptoms in Parkinson's disease (PD). METHODS: We
      searched for articles involving randomized controlled trials (RCTs) that were
      published before September 1, 2017, in the PubMed, Clinical Trials, Cochrane
      Library, and EMBASE databases. A meta-analysis was performed to estimate changes
      in the scales used to assess neuropsychiatric symptoms. The data were analyzed
      using Cochrane Collaboration's Review Manager 5.3 software. RESULTS: We
      identified 8 RCTs involving 1675 subjects. Compared with placebo treatment,
      treatment with the rotigotine transdermal patch significantly improved scores for
      the emotion/apathy domains of the Non-Motor Symptoms Scale (NMSS), Beck
      Depression Inventory-II (BDI-II), Apathy Scale (AS), the sleep/fatigue domains of
      the NMSS, the 8-item Parkinson's disease Questionnaire (PDQ-8) and the 39-item
      PDQ (PDQ-39) (emotion/apathy domain of the NMSS: MD = -2.5, 95% CI [-4.11, 0.89];
      BDI-II: MD = -1.19, 95% CI [-2.30, 0.08]; AS: MD = -1.56, 95% CI [-2.67, 0.45];
      sleep/fatigue domain of the NMSS: MD = -2.03, 95% CI [-3.08, 0.98]; PDQ-8: MD = 
      4.93, 95% CI [-6.79, 3.07]; PDQ-39: MD = -3.52, 95% CI [-5.25, 1.79]; PDQ-8 and
      PDQ-39: SMD = -0.36,95% CI [-0.49,0.23]). The results of the Parkinson's Disease
      Sleep Scale 2nd version (PDSS-2) were heterogeneous, and those on the Snaith
      Hamilton Pleasure Scale (SHAPS) were not statistically significant (P = .61).
      CONCLUSION: The rotigotine transdermal patch effectively improved
      neuropsychiatric symptoms and quality of life in patients with PD. Further
      studies are warranted.

PMID- 30099247
TI  - Derivation and numerical profile analysis of a hierarchically formulated
      microscopic model of hemoglobin oxygen binding.
AB  - To address complex thermodynamic systems with multiple interacting events, we
      have developed the concept of hierarchical thermodynamic interactions. In this
      study, this concept is extended to protein-ligand systems with similar but not
      identical protein subunits, and applied to the analysis of previously published
      NMR and UV-vis monitored hemoglobin oxygen binding data. Non-linear regression
      provided estimated errors for statistically significant parameters, but not for
      null (zero) valued parameters. A numerical/graphical profiling approach was
      therefore used to assess confidence intervals and correlations for both the
      statistically significant and nulled valued parameters in this model. Individual
      parameters were set to fixed values around their best-fit value, and the subset
      of statistically significant parameters re-minimized against hemoglobin oxygen
      binding data. Plots provide a graphical representation of parameter confidence
      intervals and correlations, and demonstrate how the two different data types - UV
      vis and NMR - constrain the range of values for each parameter. This analysis
      further illustrates the value of hierarchically formulated models for the
      analysis of complex state systems, and illuminates the complexity of parameter
      space around the derived minimum microscopic model of hemoglobin oxygen binding.

PMID- 30099248
TI  - A weighted average kinetic equation and its application in estimating mass
      transfer coefficients in liquid phase adsorption.
AB  - The pseudo-first-order (PFO) and pseudo-second-order (PSO) models are widely used
      to describe liquid phase adsorption kinetics due to their simplicity and easy
      application. But these models do not take into account the diffusion or mass
      transfer effects that exist in adsorption. In this work a new weighted average
      (WA) kinetic model is presented. The model parameters are related to mass
      transfer coefficients, which allows for the estimation of the film mass transfer
      and surface diffusion coefficients from adsorption kinetic data. The WA model is
      applied to four adsorption systems and compared with the PFO and PSO models by
      using the Akaike Information Criterion (AIC). The results show that the WA model
      fits the experimental kinetic data much better than the PFO and PSO models.

PMID- 30099249
TI  - Estimation of leakage rate of air from a fume hood in a radioisotope laboratory
      using CFD simulations.
AB  - The leakage rate of air from a fume hood is an important factor for calculating
      the internal exposure at a workplace using the dose conversion factors
      recommended by the International Atomic Energy Agency. In this study, the leakage
      rate from a fume hood was estimated in a radioisotope laboratory using
      computational fluid dynamics simulations. For this purpose, a three-dimensional
      fume hood model was built using CAD software. In this model, the leakage rate was
      calculated to be 3%, with face velocities between 0.1 and 1.0 m/s at the sash
      opening of the fume hood. This rate rapidly decreased to zero as the face
      velocities decreased to less than 0.1 m/s.

PMID- 30099250
TI  - Understand the acquired resistance of RTK inhibitors by computational receptor
      tyrosine kinases network.
AB  - Receptor Tyrosine Kinase inhibitors are the most popular anti-cancer drug types.
      But the resistance is the major challenge. Our study on the network with 1334
      proteins and their 2623 interactions which retrieved from 52 RTKs indicated that
      most RTKs proteins were the key controllers of the protein-protein network.
      Direct or indirect interactions with RTKs (shortest path of 2) were often
      associated with resistance to RTKs inhibitors in the literature. The results
      based on the KEGG pathway analysis demonstrated the Rap1 signal pathway would
      also contribute to the resistance of RTKs inhibitor as well as the known Ras
      pathway and PI3K/Akt pathway. The pathways can crosstalk within and between
      complex signals transduction networks, then activate the upstream or downstream
      pathway, and/or activate the other oncogenes, which lead to the acquired
      resistance. Our results gave a systematically global view to understand the drug
      resistance and provided a clue to how to combine the different targets or
      pathways for synergy of targeted RTKs inhibitors.

PMID- 30099251
TI  - Thiabendazole-based Rh(III) and Ir(III) biscyclometallated complexes with
      mitochondria-targeted anticancer activity and metal-sensitive photodynamic
      activity.
AB  - Two pairs of Rh(III) and Ir(III) biscyclometallated complexes with thiabendazole
      (L1), named [Ir-a]Cl and [Rh-a]Cl, and N-benzyl-thiabendazole (L2), named [Ir
      b]Cl and [Rh-b]Cl, have been designed and synthesized to explore the
      photophysical and biological effects that arise from changing both the metal
      center and the ancillary ligand. In the dark, the four metal complexes exhibit
      greater cytotoxicity than cisplatin against human colon (SW480) and human lung
      (A549) adenocarcinoma cell lines. Moreover, the pair of complexes bearing the
      ligand L2 is markedly more cytotoxic and present higher uptake values than
      complexes with L1, thereby their biological properties were studied further to
      determine their mechanism of action. Interestingly, in spite of the different
      metal center both the [Ir-b]Cl and [Rh-b]Cl complexes are responsible for the
      loss of mitochondrial functionality and the activation of apoptotic cell death
      pathways. Moreover, the photodynamic activity of the four complexes, [Ir-a,b]Cl
      and [Rh-a,b]Cl, was tested using visible blue light (460 nm) under soft
      irradiation conditions (20 min, 5.5 mW cm-2). While the Rh complexes are not
      photopotentiated, the phototoxicity index (IC50 non-irradiated/IC50 irradiated)
      of [Ir-a]Cl and [Ir-b]Cl complexes was 15.8 and 3.6, respectively. We also
      demonstrate that only the Ir derivatives are capable of photocatalyzing the
      oxidation of S-containing l-amino acids under blue light irradiation, [Ir-a]Cl
      being more active than [Ir-b]Cl, which provides a reasonable mechanism for their
      biological action (oxidative stress could be selectively promoted through a
      photocatalytic action) upon irradiation. This different PDT behaviour depending
      on the metal center and the ancillary substituent may be useful for future
      rational design of metal-based photosensitizers.

PMID- 30099252
TI  - Design and synthesis of multipotent 3-aminomethylindoles and 7-azaindoles with
      enhanced protein phosphatase 2A-activating profile and neuroprotection.
AB  - We report the synthesis and pharmacological evaluation of new 3
      aminomethylindoles derivatives with neuroprotective properties designed to
      present multi-target activity centered on reducing the neuronal Ca2+ overload and
      preventing phosphatase 2A (PP2A) inhibition, which are two important early
      physiophathological events observed in neurodegenerative scenarios. Chemical
      syntheses of proposed compounds were achieved in two straightforward reaction
      steps with high yields. Most of the compounds mitigated the okadaic acid-provoked
      inhibition of PP2A and protected SH-SY5Y cells against toxic stimuli related to
      Tau-hyperphosphorylation and oxidative stress, similarly to the observed in
      Alzheimer's disease (AD). In addition, some of them mitigated the Ca2+ overload
      induced by depolarization. The derivative 1-(1-benzyl-5-chloro-1H-indol-3-yl)-N,N
      dimethylmethanamine (19) outstood by its high recovery of the PP2A activity and
      blockade of voltage-gated Ca2+ channels, accompanied by good neuroprotective
      profile. These findings make this compound eligible for further preclinical
      assays with the goal of positioning new innovative drugs for the treatment of AD.

PMID- 30099253
TI  - Design, synthesis, docking studies and biological screening of 2-thiazolyl
      substituted -2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines as potent HIV-1 reverse
      transcriptase inhibitors.
AB  - 1,3-oxazine nucleus and thiazolyl group features prominently in many biologically
      important natural products as well as bioactive molecules. A series of novel 2
      thiazolyl substituted-2,3-dihydro-1H-naphtho [1,2-e][1,3]oxazine derivatives were
      designed and synthesized based on their structure-activity relationships (SARs)
      from 2-naphthol, substituted thiazolyl amines and formalin through ring closure
      by one-pot three component reaction. These derivatives were first evaluated for
      their inhibitory effect on HIV-1 Reverse Transcriptase (RT) enzyme activity. Out
      of 14 compounds, 4 showed potent inhibition of HIV-1 RT activity at significantly
      low concentration. Docking studies of these molecules revealed their high
      affinity binding to several amino acids of HIV-1 RT which are less sensitive to
      point mutations. Furthermore, anti-HIV activity of these molecules was analysed
      in a CD4+ T cell-line, which indicates that Therapeutic Index (TI) of some of
      these compounds is better than Zidovudine and Efavirenz, known HIV-1 RT
      inhibitors. Taken together, our studies report for the first time some novel
      naphthoxazine derivatives with significant TI, which is through inhibition of HIV
      1 RT activity.

PMID- 30099254
TI  - Pharmacomodulation on Gold-NHC complexes for anticancer applications - is
      lipophilicity the key point?
AB  - A series of four new mononuclear cationic gold(I) complexes containing nitrogen
      functionalized N-heterocyclic carbenes (NHCs) was synthesized and fully
      characterized by spectroscopic methods. The X-ray structures of three complexes
      are presented. These lipophilic gold(I) complexes originate from a
      pharmacomodulation of previously described gold(I)-NHC complexes, by replacing an
      aliphatic spacer with an aromatic one. The Log P values of the resulting
      complexes increased by 0.7-1.5, depending on the substituents in comparison to
      the aliphatic-linker systems. The new series of complexes has been investigated
      in vitro for their anti-cancer activities in PC-3 (prostate cancer) and T24
      (bladder cancer) cell lines and in the non-cancerous MC3T3 (osteoblast) cell
      line. All tested complexes show high activities against the cancer cell lines
      with GI50 values lower than 500 nM. One complex (11) has been selected for
      further investigations. It has been tested in vitro in six cancer cell lines from
      different origins (prostate, bladder, lung, bone, liver and breast) and two non
      cancerous cell lines (osteoblasts, fibroblasts). Moreover, cellular uptake
      measurements were indicative of a good bioavailability. By various biochemical
      assays, this complex was found to effectively inhibit the thioredoxin reductase
      (TrxR) and its cytotoxicity towards prostate PC-3, bladder T24 and liver HepG2
      cells was found to be ROS-dependent.

PMID- 30099255
TI  - Computer-aided drug discovery: Novel 3,9-disubstituted eudistomin U derivatives
      as potent antibacterial agents.
AB  - Thirty-two new 3,9-disubstituted eudistomin U derivatives were designed and
      synthesized based on computer-aided drug discovery (CADD). Sixteen 3,9
      disubstituted eudistomin U derivatives (6a-6p) have exhibited potent
      antibacterial activity. Specially, the most active compound 6p displayed better
      activity than commercial drugs fosfomycin sodium, ciprofloxacin and propineb,
      with a peak minimum inhibitory concentration (MIC) of 1.5625 MUmol/L. The
      antibacterial mechanism indicated that these compounds could exert bactericidal
      effect by damaging bacterial cell membrane and disrupting the function of DNA
      gyrase.

PMID- 30099256
TI  - An update on small molecule strategies targeting leishmaniasis.
AB  - Leishmaniasis is an infectious disease caused by various species of protozoan
      parasite known as Leishmania, which is transmitted to its mammalian host via bite
      of an infected sandfly. Clinically, Leishmaniasis appears as following four
      conditions: Cutaneous Leishmaniasis, Mucocutaneous Leishmaniasis, Visceral
      Leishmaniasis/Kala-azar, Post Kala azar dermal Leishmaniasis. Current therapies
      include pentavalent antimonials, Amphotericin B, Paromomycin, Miltefosine,
      Pentamidine, Sitamaquine. Presence of diverse survival pathways in the parasite
      to carry out various physiological functions has rendered targeting via drugs
      inefficient and troublesome. Moreover, emerging resistance mechanisms in the well
      established key targets are affecting the use of current drug treatment options
      thus leading to treatment failure. Therefore, development of novel anti
      leishmanial compounds with alternative and efficient mechanisms of actions is
      required to eradicate this disease. This review provides an overview of
      leishmaniasis along with the main emphasis on novel heterocycles reported for
      their anti-leishmanial activity in recent years.

PMID- 30099257
TI  - Hedgehog pathway inhibitors of the acylthiourea and acylguanidine class show
      antitumor activity on colon cancer in vitro and in vivo.
AB  - Small series of acylguanidine and acylthiourea derivatives were synthesized in
      gram-scale and assayed for their ability to modulate the Hh signalling pathway.
      In vitro studies showed a low micromolar inhibitory activity toward tumor cell
      lines, while the oral administration revealed an excellent ADME profile in vivo.
      Compound 5 emerged as the most active and safe inhibitor of colon cancer cells
      both in vitro and in a xenograft mouse model. Based on these data, 5 could be
      prioritized to further development with the perspective of clinical studies.

PMID- 30099258
TI  - Design, synthesis and characterization of potent microtubule inhibitors with dual
      anti-proliferative and anti-angiogenic activities.
AB  - Microtubule has been an important target for anticancer drug development. Here we
      report the discovery and characterization of a series of fused 4-aryl-4H-chromene
      based derivatives as highly potent microtubule inhibitors. Among a total of 37
      derivatives synthesized, 23 exhibited strong in vitro anti-proliferative
      activities against A375 human melanoma cells. The relationship between the
      biological activities of these microtubule inhibitors and their chemical
      structure variations was analyzed. Studies of compounds 27a, 19a and 9a in
      parallel with colchicine as the positive control compound in a panel of
      biological assays revealed that these compounds blocked cell cycle progression,
      increased apoptosis, and inhibited HUVEC capillary tube formation at low
      nanomolar concentrations. The most potent compound 27a was also tested in eight
      additional cancer cell lines besides A375 cells and two non-cancer cells and
      showed potent and selective activity on these cancer cells. To understand the
      molecular and structure mechanism of action of these compounds, tubulin
      polymerization and molecular docking studies were carried out for 27a as the
      representative. The results were consistent with the mechanism by which 27a
      interacts with the colchicine binding site on tubulin and disrupts tubulin
      polymerization. With potent dual actions of microtubule destabilization and
      vascular disruption described above, this small molecule can serve as a valuable
      research probe of the function and role of microtubules in human diseases and
      promising lead for developing new therapeutic agents.

PMID- 30099259
TI  - "Anywhere but here": Querying spatial stigma as a social determinant of health
      among youth of color accessing LGBTQ services in Chicago's Boystown.
AB  - The link between stigma and negative health outcomes is established, yet
      available research infrequently considers the complex intersection of place,
      race, and class-based stigma and how this stigma shapes opportunities and health
      among marginalized groups. Furthermore, scholarship on the relationship between
      stigma and health often fails to include the voices of the stigmatized
      themselves. This exclusion renders their lived-experiences hidden and their
      insight devalued, producing findings with limited validity to promote health
      equity and social change. In this article, we explore intersecting place, race,
      and class-based stigmas, or spatial stigma, as a social determinant of health
      among youth of color (YoC) accessing LGBTQ-specific services in the Chicago's
      White, middle-class gay enclave, Boystown. Qualitative data were collected within
      the context of a youth participatory action research study with 11 youth
      researchers (ages 18-24). Data sources included critical autoethnography, focus
      groups with current and former LGBTQ service patrons, and individual interviews
      with LGBTQ service providers. Emergent thematic patterns illuminate how the
      stigmatization of YoC based on place, race, and class (i.e., being from poor and
      low-income, racialized South and West sides communities) impacts their
      opportunities in the neighborhood and access to health-supporting resources.
      These findings may be useful for practitioners and policy makers who aim to
      promote health equity among marginalized young people and add to the growing body
      of literature on health effects of spatial stigma among marginalized communities.

PMID- 30099260
TI  - Long-acting liposomal corneal anesthetics.
AB  - Eye drops producing long-acting ocular anesthesia would be desirable for corneal
      pain management. Here we present liposome-based formulations to achieve very long
      ocular anesthetic effect after a single eye drop instillation. The liposomes were
      functionalized with succinyl-Concanavalin A (sConA-Lip), which can bind corneal
      glycan moieties, to significantly prolong the dwell time of liposomes on the
      cornea. sConA-Lip were loaded with tetrodotoxin and dexmedetomidine (sConA
      Lip/TD), and provided sustained release for both. A single topical instillation
      of sConA-Lip/TD on the cornea could achieve 105 min of complete analgesia and 608
      min of partial analgesia, which was significantly longer than analgesia with
      proparacaine, tetrodotoxin/dexmedetomidine solution or unmodified liposomes
      containing tetrodotoxin and dexmedetomidine. sConA-Lip/TD were not cytotoxic in
      vitro to human corneal limbal epithelial cells or corneal keratocytes. Topical
      administration of sConA-Lip/TD provided prolonged corneal anesthesia without
      delaying corneal wound healing. Such a formulation may be useful for the
      management of acute surgical and nonsurgical corneal pain, or for treatment of
      other ocular surface diseases.

PMID- 30099261
TI  - Long-acting hydrogel/microsphere composite sequentially releases dexmedetomidine
      and bupivacaine for prolonged synergistic analgesia.
AB  - Local anesthetics are a class of drugs, which have wide applications in the
      treatment of acute and chronic pain. However, their analgesic effects only last
      for a few hours because of their short half-life, which is insufficient for
      clinical application, especially for long-term surgery or postoperative
      analgesia. Herein, an injectable hydrogel/microsphere (GEL/MS) composite co
      encapsulating bupivacaine (BUP) and dexmedetomidine (DEX) was developed for
      effective sustained analgesia. The GEL/MS composite appeared as a three
      dimensional porous network microstructure and displayed sustained sequential
      release of DEX and BUP over several days in vitro, without obvious burst release.
      In this composite, DEX was released from the GEL matrix preferentially, exhibited
      long-term vasoconstriction effect and improved the local anesthetic concentration
      at injection site by preventing BUP from diffusing into the blood circulation.
      BUP was released subsequently from the MS for blockage of the Na+ channel on
      nerve cell membranes and provided long-term analgesia. In vivo analgesic effect
      demonstrated that DEX significantly prolonged the effect of analgesia when
      synergistically administered with BUP in the GEL/MS composite. Moreover, the
      GEL/MS composite exhibited good biodegradability and biocompatibility in
      histological analyses. Taken together, the administration of BUP and DEX in the
      GEL/MS composite achieved a synergistic effect in prolonging analgesia without
      causing toxicity, and thus represented a potential strategy for long-acting
      analgesia therapy.

PMID- 30099262
TI  - Gene expression profile associated with thymus regeneration in dexamethasone
      treated beef cattle.
AB  - Glucocorticoids (GCs) are illegally used as growth promoters in cattle, and the
      analytical methods officially applied most likely underestimate the precise
      frequency of the abuse. As a side effect, the administration of GCs causes fat
      infiltration, apoptosis, and atrophy of the thymus. However, gross and
      histological observations carried out previously showed that the thymus preserves
      an intrinsic ability to regenerate. The aim of this work was to study the
      transcriptional effects of GCs on genes likely involved in regeneration of the
      epithelial cell network in the cervical and thoracic thymus of beef cattle
      treated with dexamethasone (DEX) or prednisolone (PRD) in comparison with a
      control group. Moreover, the ratio of bax/bcl2 genes was examined to verify a
      possible antiapoptotic activity occurring at the same time. In the cervical
      thymus, DEX administration increased the gene expression of c-myc (P < 0.01),
      tcf3 (P < 0.05), tp63 (P < 0.01), and keratin 5 (krt5; P < 0.01). In the thoracic
      thymus of DEX-treated cattle, the gene expression of tcf3 (P < 0.01), tp63 (P <
      0.01), and krt5 (P < 0.05) was increased. These results suggested that thymic
      regeneration is underway in the DEX-treated animals. However, the bax/bcl2 ratio
      was decreased in both cervical and thoracic thymus of DEX-treated cattle (P <
      0.01 and P < 0.05, respectively), showing an antiapoptotic effect through the
      mitochondrial pathway. Conversely, PRD administration caused no change in the
      expression of all considered genes. These results sustain the hypothesis that
      regeneration occurs in the thymus parenchyma 6 d after the DEX treatment was
      discontinued. This hypothesis is also supported by the absence of alterations in
      the thymus of PRD-treated beef cattle. Indeed, previous studies showed the
      inability of PRD to induce macroscopic and microscopic lesions in the thymus.
      Therefore, in this context, it is not surprising that PRD induced no alteration
      of genes involved in the regeneration pathway.

PMID- 30099263
TI  - The origins of cortical multisensory dynamics: Evidence from human infants.
AB  - Classic views of multisensory processing suggest that cortical sensory regions
      are specialized. More recent views argue that cortical sensory regions are
      inherently multisensory. To date, there are no published neuroimaging data that
      directly test these claims in infancy. Here we used fNIRS to show that temporal
      and occipital cortex are functionally coupled in 3.5-5-month-old infants (N =
      65), and that the extent of this coupling during a synchronous, but not an
      asynchronous, audiovisual event predicted whether occipital cortex would
      subsequently respond to sound-only information. These data suggest that
      multisensory experience may shape cortical dynamics to adapt to the ubiquity of
      synchronous multisensory information in the environment, and invoke the
      possibility that adaptation to the environment can also reflect broadening of the
      computational range of sensory systems.

PMID- 30099264
TI  - Diagnostic and surgical challenges of a giant pheochromocytoma in a resource
      limited setting-A case report.
AB  - INTRODUCTION: Pheochromocytomas are catecholamine producing tumours which arise
      from chromaffin cells within the adrenal medulla. Patients with these tumours
      commonly present with a triad of headache, palpitations and hypertension. CASE
      PRESENTATION: We present a case of a 37-year-old male patient who presented with
      dull left sided abdominal pain and discomfort for 6 weeks. A preoperative
      Computed tomography (CT) scan showed a huge left suprarenal tumour but urinary
      vanillylmandelic acid (VMA) were negative. The patient underwent an open surgical
      resection via an extraperitoneal approach without untoward intraoperative and
      postoperative events. Histopathological evaluation of the specimen showed a
      pheochromocytoma with a PASS score of 9. The successful management of the patient
      highlights the good results of team work despite the limitations of preoperative
      diagnosis. DISCUSSION: Giant pheochromocytomas by definition are tumours more
      than 7 cm in size and are rare. They rarely secrete catecholamines and commonly
      present with vague abdominal symptoms. A computerized tomogram helps suggest the
      diagnosis whilst the biochemical workup for pheochromocytoma may be diagnostic.
      If the tumours are biochemically active, preoperative alpha-blockade is necessary
      and care must be taken at operation in handling the tumour. The surgical and
      anaesthetic team must be prepared to manage hypertensive crisis should it occur.
      CONCLUSION: This case brings to the attention of clinicians the need to have a
      high index of suspicion of a giant pheochromocytoma in a patient presenting with
      vague abdominal symptoms whose CT scan shows a large retroperitoneal tumour, even
      in the absence of clinical symptoms and negative or absent biochemical workup.

PMID- 30099265
TI  - Small bowel obstruction due to a phytobezoar thirty years after Roux-en-Y
      gastrojejunostomy: A case report.
AB  - INTRODUCTION: We present a case of a delayed small bowel obstruction due to a
      phytobezoar in a patient with a previous surgical history. PRESENTATION OF CASE:
      A 73-year-old male patient presented with vomiting and obstipation for a week.
      His past surgical history included a Roux-en-y gastrojejunostomy due to a
      surgical management for peptic ulcer disease 30 years ago. Abdominal computed
      tomography demonstrated a dilation of small bowel with air-fluid levels. He was
      diagnosed with acute bowel obstruction. On exploration, we found a compressible
      mass 150 cm from the jejunojejunostomy anastomosis. An enterotomy was performed
      and the mass was milked back. It was a phytobezoar. After the bezoar removal, his
      complaints relieved completely. DISCUSSION: Small bowel obstruction after
      abdominal surgery (Roux-en-y gastrojejunostomy) is a complication that may
      present early or late for many causes. One of the unusual underlying causes is
      phytobezoar. CONCLUSION: This case aims to raise awareness of phytobezoar as a
      cause of small bowel obstruction even in delayed presentation.

PMID- 30099266
TI  - Excess lung cancer occurrence in poultry plants. Occupational risk factors:
      Findings for oncogenic viruses exposure and other occupational exposures.
AB  - Certain viruses naturally infect and cause cancer in chickens and turkeys. Humans
      are widely exposed. The viruses cause cancer in primates, and transform human
      cells in vitro, but it is not known if they cause cancer in humans, mainly
      because of the lack of epidemiologic evidence. We conducted cohort mortality
      studies of workers in poultry slaughtering/processing plants across the United
      States, because they have the highest human exposures. An excess of lung cancer
      and other deaths was recorded in the poultry workers. Here, we report on a case
      cohort study of the lung cancer deaths nested within these cohorts, that was
      conducted to provide epidemiologic evidence linking these viruses with human
      cancer occurrence, while adjusting for possible confounders, including workplace
      chemical carcinogens. We obtained interviews for 339 lung cancer deaths and 457
      controls, selected from our combined cohorts of 30,411 poultry plant workers and
      16,405 non-poultry workers, belonging to United Food & Commercial Workers unions.
      Data was analyzed by both logistic regression and Cox regression, adjusting for
      smoking and other confounders. Lung cancer risk was independently associated with
      tasks or work areas indicative of exposure to both poultry oncogenic viruses and
      to workplace chemical carcinogens. The study provides an incremental piece of
      evidence (epidemiologic), indirectly linking the oncogenic viruses of poultry
      with the occurrence of cancer in humans, and thus may have public health
      implications, but the limitations highlighted must be considered. Confirmatory
      studies, particularly molecular studies providing definitive proof of poultry
      oncogenic retrovirus integration in human DNA are needed, before the findings
      observed in this study can be put into proper perspective.

PMID- 30099267
TI  - Child maltreatment, psychopathological symptoms, and onset of diabetes mellitus,
      hypothyroidism and COPD in adulthood.
AB  - BACKGROUND: The aim of this study was to assess the associations between child
      maltreatment (CM), psychopathological symptoms, and onset of diabetes mellitus,
      hypothyroidism (i.e., low metabolism), and chronic bronchitis/emphysema/COPD in
      adulthood. METHODS: The present analysis used cross-sectional data collected in
      2007-2008 within the Tromso Study, Norway (N = 12,981). CM was measured with a
      single item, and self-reported information on psychopathological symptoms and
      physical health outcomes was used. The associations between CM,
      psychopathological symptoms, and physical health outcomes were assessed with
      linear and Poisson regression models. Mediation was assessed with difference-in
      coefficients method. RESULTS: In the fully-adjusted models, CM was associated
      with higher levels of anxiety and depression, psychological distress, difficulty
      in sleeping, insomnia, and use of sleeping pills and antidepressants in adulthood
      (p < 0.05). Moreover, CM was associated with a more than two-folds increased risk
      of consultation with psychiatrist (p < 0.001), a 26% increased risk of
      forgetfulness (p < 0.001), a 15% increased risk of decline in memory (p < 0.001),
      and a 96% increased risk of psychiatric problems (p < 0.001) over the course of
      life. In the fully-adjusted models, CM was associated with a 27-82% increased
      risk of physical health outcomes in adulthood (p < 0.05). Indicators of
      psychopathological symptoms significantly (p < 0.05) mediate the associations
      between CM and physical health outcomes. LIMITATIONS: The design of this study is
      cross-sectional, and all measures are self-reported. CONCLUSION: The associations
      between retrospectively-reported CM and physical health outcomes in adulthood are
      partially driven by psychopathological symptoms in adulthood.

PMID- 30099268
TI  - Characterizing the course of suicidal ideation response to ketamine.
AB  - BACKGROUND: No pharmacological treatments exist for active suicidal ideation
      (SI), but the glutamatergic modulator ketamine elicits rapid changes in SI. We
      developed data-driven subgroups of SI trajectories after ketamine administration,
      then evaluated clinical, demographic, and neurobiological factors that might
      predict SI response to ketamine. METHODS: Data were pooled from five clinical
      ketamine trials. Treatment-resistant inpatients (n = 128) with DSM-IV-TR
      diagnosed major depressive disorder (MDD) or bipolar depression received one
      subanesthetic (0.5 mg/kg) ketamine infusion over 40 min. Composite SI variable
      scores were analyzed using growth mixture modeling to generate SI response
      classes, and class membership predictors were evaluated using multinomial
      logistic regressions. Putative predictors included demographic variables and
      various peripheral plasma markers. RESULTS: The best-fitting growth mixture model
      comprised three classes: Non-Responders (29%), Responders (44%), and Remitters
      (27%). For Responders and Remitters, maximal improvements were achieved by Day 1.
      Improvements in SI occurred independently of improvements in a composite
      Depressed Mood variable for Responders, and partially independently for
      Remitters. Indicators of chronic SI and self-injury were associated with
      belonging to the Non-Responder group. Higher levels of baseline plasma
      interleukin-5 (IL-5) were linked to Remitters rather than Responders.
      LIMITATIONS: Subjects were not selected for active suicidal thoughts; findings
      only extend to Day 3; and plasma, rather than CSF, markers were used. CONCLUSION:
      The results underscore the heterogeneity of SI response to ketamine and its
      potential independence from changes in Depressed Mood. Individuals reporting
      symptoms suggesting a longstanding history of chronic SI were less likely to
      respond or remit post-ketamine.

PMID- 30099270
TI  - Investigating the efficacy of a new intravenous (IV) nanoemulsified
      sevoflurane/arginine formulation for maintenance of general anesthesia for
      embolization of cerebral aneurysm.
AB  - The aim of this research investigation was to profound analysis the mitigating
      impact of sevoflurane/arginine post-molding on cerebral ischemia-reperfusion
      damage in rats. The authors fabricated emulsions fusing sevoflurane,
      perfluorooctyl bromide as a settling specialist, and mixes of arginine polymer.
      Cell suitability and gene expression of tubulin and NeuN were assessed. The
      stability, morphology and functional group were evaluated utilizing dynamic light
      scattering (DLS), Transmission Electron Microscope (TEM), atomic force microscopy
      (AFM), and Fourier-transform infrared spectroscopy (FTIR). Cerebral aneurysms
      were prompted through hypertension and a solitary stereotactic infusion of
      elastase into the basal storage in rat. The capacity of the emulsions to
      decreased cerebral aneurysm was tried in vivo by regulating them IV delivery of
      Se/Arg samples to rats. Se/Arg pre-conditioning expanded cell feasibility in
      neuroblast (SK-N-DZ) cells. Se/Arg pre-conditioning diminished infarct volume and
      enhanced neurological result in rats subjected to cerebral hypoxia-ischemia.
      Se/Arg preconditioning expanded levels of tubulin and NeuN. The prepared
      sevoflurane/arginine material pre-conditioning-incited neuroprotective impacts in
      vitro as well as in vivo analyses. Sevoflurane/arginine post-molding decreased
      cerebral tissue misfortune detected 7 days after cerebrum hypoxia-ischemia. This
      impact was prompted by clinically significant focuses and canceled by
      Sevoflurane/arginine. These outcomes recommend that Sevoflurane/arginine post
      conditioning ensures neonatal cerebrum against cerebrum hypoxia-ischemia.

PMID- 30099269
TI  - Enhanced wound healing activity of PEG/PCL copolymer combined with bioactive
      nanoparticles in wound care after anorectal surgery: Via bio-inspired
      methodology.
AB  - Over the past decade, the implementation of the novel nanomaterials in the field
      of nanotechnology for the biomedical applications is essential for the comfort
      factors such as non-toxicity and biocompatibility in the human biological
      systems. In this context, a novel synthesis was worked out through bacterial
      species (citrobacter braakii) in the biofabrication of bioactive gold
      nanoparticles (Au NPs) for the wound healing management. The biosynthesized Au
      NPs were further modified and improved its compatibility with polyethylene glycol
      (PEG) and polycaprolactone (PCL) for formed as Au-PEG/PCL nanocomposites to
      extent the activity in wound healing application. The combination of bioactive
      nanoparticles with biocompatible polymeric substances has been upsurges the
      activity of nanoparticles due to the strong interaction of polymers. The
      biofabricated Au NPs and its nanocomposites were characterized using UV-Vis, FT
      IR, XRD, DLS and TEM studies. Further, the prepared materials were tested in a
      wound healing model of rat with the wound of 22 mm size. The found results are
      demonstrated that the improved materials are highly active in growth of
      keratinocytes proliferation and simultaneously reduce scar formation. After 15
      days observations, the wound were almost completely healed by the developed Au-
      PEG/PCL nanocomposites material which was confirmed by Masson's Trichrome
      staining histological images and antibacterial efficacy was displayed by the CLSM
      images. Notably, polymeric Au-PEG/PCL nanocomposites showed no inflammation on
      the wounded portion and internal implantation on rats thus evidencing it as a
      safe and biologically very active wound healing agent.

PMID- 30099271
TI  - Visible light responsive flower-like ZnO in photocatalytic antibacterial
      mechanism towards Enterococcus faecalis and Micrococcus luteus.
AB  - Flower-like ZnO micro/nanostructures were successfully fabricated via a
      surfactant-free co-precipitation method. The as-synthesized product was
      characterized using X-ray diffraction (XRD), field emission scanning electron
      microscopy (FESEM), energy dispersive X-ray (EDX), transmission electron
      microscopy (TEM), fourier transform infrared spectroscopy (FTIR), UV-vis diffuse
      reflectance spectroscopy (UV-vis DRS) and photoluminescence (PL) analyses. In the
      presence of visible light irradiation, the as-synthesized flower-like ZnO showed
      higher antibacterial activities against Enterococcus faecalis (E. faecalis) and
      Micrococcus luteus (M. luteus) than that of commercial ZnO. The excellent
      antibacterial performance of synthesized flower-like ZnO was also observed via
      the bacterial morphological change, K+ ions leakage and protein leakage in
      extracellular suspension. In addition, the FTIR investigation on both treated
      bacteria further confirmed the bacterial membrane damage via cellular substance
      alteration. The enhancement of the antibacterial activity of synthesized ZnO can
      be attributed to the unique flower-like morphology which can increase the surface
      OH- groups and the quantity of photogenerated electron-hole pair available to
      participate in the photocatalytic reaction. The reactive oxidizing species (ROS)
      scavengers experiments showed that H2O2 played a main role in the photocatalytic
      antibacterial process. Our study showed that the synthesized flower-like ZnO
      micro/nanostructures can act as efficient antibacterial agents in the
      photocatalytic antibacterial process under visible light irradiation.

PMID- 30099272
TI  - Dibenzoxanthenes induce apoptosis and autophagy in HeLa cells by modeling the
      PI3K/Akt pathway.
AB  - A new series of dibenzoxanthene derivatives 4a-4d (4a: 1-oxo-5-bromo-11-cyano-13c
      methoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene, 4b: 1-oxo-5-bromo-11-cyano-13c
      ethoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene, 4c: 1-oxo-5-bromo-11-cyano-13c
      propoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene and 4d: 1-oxo-5-bromo-11-cyano-13c
      butoxy-1,13c-dihydroxyl-dibenzo[a,kl]xanthene) were synthesized and the molecular
      mechanisms of anti-cancer activities were investigated. These compounds showed
      excellent anti-tumor activity against A549, Eca-109, HeLa, HepG2 and SGC-7901
      cell lines. Compounds 4a-4d could effectively inhibit the migration and invasion
      of HeLa cells in wound healing and transwell assays. Compounds induced the DNA
      damage and arrested in cell cycle distribution at G0/G1 phase. Apoptosis induced
      by compounds was detected using morphological observation of nuclear changes and
      FITC-Annexin V/PI staining. Additionally, compounds also induced the autophagy of
      HeLa cells through observing AO staining and upregulated the expression of LC3II
      and Beclin-1 proteins. Furthermore, treatment with autophagy inhibitor 3
      methyladenine induced an obvious decrease in apoptotic rate in HeLa cells. This
      indicated that autophagy further promoted the HeLa cells apoptosis. Compounds 4a
      4d enhanced the intracellular Ca2+ and ROS. Then the mitochondrial membrane
      potential of HeLa cells was depolarized and the cytochrome C was released from
      mitochondria into cytoplasm. Activities of the apoptotic factors Bcl-2, Bax,
      caspase-3 were measured using western blotting. After HeLa cells were exposed to
      compounds, the expressions of PI3K and Akt protein were decreased. Compounds
      exhibit anti-cancer activity via apoptosis and autophagy through inhibition of
      PI3K/Akt signaling pathway in HeLa cells.

PMID- 30099273
TI  - Exogenous 24-Epibrassinolide alleviates oxidative damage from copper stress in
      grape (Vitis vinifera L.) cuttings.
AB  - Copper (Cu) stress is the most common abiotic stress experienced in vineyards
      owing to the copper-based fungicides application. Plant hormones, including 24
      Epibrassinolide (EBR), may alleviate the adverse impacts of heavy metal stress on
      plants. We investigated the effects of EBR pretreatment on root morphological
      parameters, active oxygen metabolism, osmolytes contents, antioxidant enzyme
      activity, endogenous phytohormone contents, and ascorbate-glutathione (AsA-GSH)
      cycle activity of one-year-old grape (Vitis vinifera L.) cuttings under Cu
      stress. Pretreatment with EBR significantly enhanced root morphological
      parameters (total root length, root surface area, root diameter, root volume, and
      tip number), increased soluble protein and proline contents, and significantly
      decreased the contents of H2O2, O2?-, and malondialdehyde (MDA) in roots and
      leaves. EBR pretreatment increased the activities of superoxide dismutase (SOD),
      catalase (CAT), peroxidase oxidase (POD), and the contents of the endogenous
      phytohormones abscisic acid, jasmonic acid, and salicylic acid in the leaves. In
      addition, EBR regulated the balance of the AsA-GSH cycle by increasing the
      activities of monodehydroascorbate reductase (MDHAR), glutathione peroxidase
      (GR), ascorbate peroxidase (APX), and dehydroascorbate reductase (DHAR), and the
      contents of the antioxidant ascorbate (AsA) and dehydroascorbic acid (DHA), but
      the contents of glutathione (GSH) and oxidized glutathione (GSSG) decreased.
      Among the treatments tested, pretreatment with 0.10 mg/L EBR showed the optimal
      performance for alleviation of Cu toxicity. The results show that exogenous
      brassinosteroids reduce oxidative damage and improve the tolerance of Cu stress
      of grapevine cuttings.

PMID- 30099275
TI  - More intensive probing increases the detection of social anxiety disorders in
      schizophrenia.
AB  - This study examined the influence of the assessment methods in detecting social
      anxiety disorders (SAD). We used a two-stage procedure to elicit social anxiety
      symptoms (SAS) to diagnose SAD in 80 people with a schizophrenia spectrum
      psychotic disorder (SZSPD) from an early intervention program. We observed a
      28.8% lifetime prevalence of SAD when considering only the SAS elicited using the
      SCID probes (first stage), and a significant increase to 48.8% after adding the
      probes from the Liebowitz Social Anxiety Scale (second stage). In conclusion, the
      LSAS can increase the sensitivity in detecting SAS and hence SAD comorbid to
      SZSPD.

PMID- 30099274
TI  - Effect of delayed cord clamping on very preterm twins.
AB  - BACKGROUND: The very preterm infants of twin births may particularly benefit from
      delayed cord clamping (DCC) as the likelihood of unfavorable outcome is greater
      compared to singletons. Unfortunately, there is paucity of available information
      regarding safety and efficacy of DCC in this group. OBJECTIVE: To report the
      clinical consequences of delayed cord clamping (DCC) in very preterm twins, born
      between 230/7 and 316/7 weeks gestation. STUDY DESIGN: In this pre and post
      intervention retrospective cohort study, we compared 30 very preterm infants born
      from 15 twin deliveries during historic study period to 32 very preterm infants
      born from 16 twin deliveries during DCC study period. During historic study
      period (August 19, 2013 to January 31, 2015), infants included were eligible to
      receive DCC, but their cords were immediately clamped. DCC study period (February
      1, 2015 to January 31, 2017) included infants who had DCC performed for 60 s
      after birth. RESULTS: The Apgar scores and other resuscitation variables were
      similar between both groups. After adjusting for gestational age and mode of
      delivery, significantly fewer infants in the DCC cohort needed red blood cell
      (RBC) transfusions in first week of life compared to the historic cohort (15.6%
      vs. 43.3%; P = 0.03). Death and other major neonatal outcomes were similar
      between both groups. CONCLUSION: DCC in very preterm twins was safe, feasible and
      not associated with any adverse neonatal outcomes compared to early cord
      clamping. DCC was associated with a significant reduction in early RBC
      transfusions.

PMID- 30099276
TI  - The relationship between theory of mind deficits and neurocognition in first
      episode-psychosis.
AB  - Research suggests that theory of mind (ToM) deficits are related to chronic
      psychosis and to first-episode psychosis (FEP) independently of other
      neurocognition domains. The aim of this study was to measure the differences in
      ToM area in a Spanish population of FEP sample (N = 32) and in a healthy control
      group (N = 32). A further aim was to describe the relationship between different
      domains of neurocognition, psychotic symptoms and social functioning with ToM in
      this sample. ToM was assessed with the MASC task. Estimated IQ with a short
      version of the WAIS III, Rey-Osterrieth Complex figure, Trail Making Test, Stroop
      test and Wisconsin Carting Sorting test were used to assess neurocognition.
      Psychotic symptoms were assessed with Community Assessment of Psychic Experiences
      (CAPE) in both groups and with PANSS scale in FEP group. GAF and Cannon-Spoor
      scales were used to measure social functioning before and after onset of
      psychosis. FEP showed important deficits in ToM domain compared to controls. A
      worse executive functioning was associated with worse scores in ToM task.
      However, no relation was found between positive or negative psychotic symptoms
      and ToM or social functioning and ToM. In our sample neurocognition tests were
      strongly related to ToM domain independently of other variables.

PMID- 30099277
TI  - A synthetic polymeric biolubricant imparts chondroprotection in a rat meniscal
      tear model.
AB  - Intra-articular injection of hyaluronic acid (HA) is used to treat osteoarthritis
      (OA) as a viscosupplement, yet it only provides short-term benefit because HA is
      cleaved by hyaluronidase and cleared out of the joint after several days.
      Therefore, we developed a new polymer biolubricant based on poly-oxanorbornane
      carboxylate to enhance joint lubrication for a prolonged time. Rheological and
      biotribological studies of the biolubricant reveal viscoelastic properties and
      coefficient of friction equivalent and superior to that of healthy synovial
      fluid, respectively. Furthermore, in an ex vivo bovine cartilage plug model, the
      biolubricant exhibits superior long-term reduction of friction and wear
      prevention compared to saline and healthy synovial fluid. ISO 10993
      biocompatibility tests demonstrate that the biolubricant polymer is non-toxic. In
      an in vivo rat medial meniscal tear OA model, where the performance of the
      leading HA viscosupplement (Synvisc-one(r)) is comparable to the saline control,
      treatment with the biolubricant affords significant chondroprotection compared to
      the saline control.

PMID- 30099279
TI  - Perceptions of mental health and mental health services among college students in
      Vietnam and the United States.
AB  - The global burden of mental health disorders is a significant public health
      issue. One population that has a risk for mental health issues is college
      students. Little is known about perceptions of mental illness and mental health
      services among college students in Vietnam. The purpose of this study is to
      describe perceptions of mental illness and mental health services among college
      students in Vietnam, and to compare them with those in the United States (US).
      The cross-sectional data were collected using a self-administered survey from
      January to March in 2018 at a national university in Vietnam, and a state
      university in the US. The study revealed differences in perceptions of causes of
      mental health between Vietnamese and US participants. Vietnamese participants
      tended to believe that individuals with mental illness were dangerous and need to
      be kept out from the community, while US participants perceived that mental
      illnesses are the same as other illnesses. An important indicator of Vietnamese
      perceptions of mental health was the low likelihood of seeking formal help
      because of preference for seeking help from family or friends for mental illness.
      Interventions, such as mental health awareness campaigns or training courses
      should be provided for college students in Vietnam. Some strategies to improve
      mental health among college students used in the US may help to reduce stigma
      toward mental illness in Vietnam.

PMID- 30099278
TI  - Coupling of a specific photoreactive triple-helical peptide to crosslinked
      collagen films restores binding and activation of DDR2 and VWF.
AB  - Collagen-based scaffolds may require chemical crosslinking to achieve mechanical
      properties suitable for tissue engineering. Carbodiimide treatment, often used
      for this purpose, consumes amino acid side chains required for receptor
      recognition, thus reducing cell-collagen interaction. Here, we restore
      recognition and function of both von Willebrand Factor (VWF) and Discoidin Domain
      Receptor 2 (DDR2) to crosslinked collagen films by derivatisation with a specific
      triple-helical peptide (THP), an approach previously applied to integrin-mediated
      cellular adhesion. The THP contained the collagen III-derived active sequence,
      GPRGQOGVNleGFO, conjugated to a photoreactive moiety, diazirine, allowing UV
      dependent covalent coupling to collagen films. Crosslinking of collagen films
      attenuated the binding of recombinant VWF A3 domain and of DDR2 (as the GST and
      Fc fusions, respectively), and coupling of the specific THP restored their
      attachment. These derivatised films supported activation of DDR2 expressed in
      either COS-7 or HEK293 cells, reflected by phosphorylation of tyrosine 740, and
      VWF-mediated platelet deposition from flowing blood was restored. Further, such
      films were able to increase low-density lipoprotein uptake in vascular
      endothelial cells, a marker for endothelial phenotype. Thus, covalent linkage of
      specific THPs to crosslinked collagen films i) restores their cognate protein
      binding, ii) triggers the corresponding cellular responses, and iii) demonstrates
      the broad applicability of the approach to a range of receptors for applications
      in regenerative medicine.

PMID- 30099280
TI  - Directional brain networks underlying OM chanting.
AB  - OM chanting is an ancient technique of Indian meditation. OM chanting is
      associated with an experience of relaxation, changes in autonomic balance and
      deactivation of limbic brain regions. While functional localization is important,
      how brain regions interact with each other has been shown to underlie various
      brain functions. Therefore, in this study, we tested the hypothesis that there is
      reduced communication between deactivated regions during OM chanting. In order to
      do so, we employed multivariate autoregressive model (MVAR) based Granger
      causality to obtain directional connectivity between deactivated regions. fMRI
      scans of 12 right handed healthy volunteers (9 Men) from a previously published
      study was used in which participants performed OM chanting and a control
      condition in a block design. We found that outputs from insula, anterior
      cingulate and orbitofrontal cortices were significantly reduced in OM condition.
      Of interest is the reduction of outputs from these regions to limbic area
      amygdala. Modulation of brain regions involved in emotion processing and
      implicated in major depressive disorder (MDD) raises a potential possibility of
      OM chanting in the treatment of MDD.

PMID- 30099281
TI  - Control of Staphylococcus aureus biofilms by the application of single and
      combined treatments based in plant essential oils.
AB  - Effective and environmentally-friendly alternatives to traditional disinfectants
      are necessary to reduce the pollution and the emergence of antimicrobial
      resistant bacterial strains in food-related environments. In the present study,
      treatments based in single and combined applications of plant essential oils
      (EOs) were evaluated for control Staphylococcus aureus biofilms. EOs of Lippia
      sidoides, Thymus vulgaris and Pimenta pseudochariophyllus showed a higher
      efficacy than peracetic acid and sodium hypochlorite against S. aureus planktonic
      cells and 24-h-old biofilms formed on polystyrene and stainless steel under food
      related conditions. High concentrations of thymol and chavibetol were detected in
      these EOs, as well as the presence of other antimicrobial compounds such as
      carvacrol, eugenol, p-cymene, limonene, alpha-pinene, alpha-terpineol, terpinen-4
      oil and linalool. L. sidoides oil were particularly effective against S. aureus,
      but doses higher than 2.75% (v/v) were required to completely eradicate 24-h-old
      biofilms. Binary combinations of L. sidoides, T. vulgaris and P.
      pseudochariophyllus allowed decrease significantly doses required to reduce
      99.99% the number of biofilm cells. Furthermore, peracetic acid increased its
      efficacy against S. aureus biofilms by the combined application with these EOs.
      The most effective treatments against S. aureus biofilms were those combining L.
      sidoides with T. vulgaris or peracetic acid. Therefore, these EO-based treatments
      can be considered as an effective and environmentally-friendly alternative to
      control S. aureus biofilms in food-contact surfaces.

PMID- 30099282
TI  - Molecular response of Vibrio parahaemolyticus to the sanitizer peracetic acid.
AB  - Peracetic acid (PAA) is a common oxidative sanitizer that is used in the food
      industry against various microorganisms. Limited information on the response of
      bacteria to this biocide is available. This study investigates the molecular
      response of the prevalent seafood-borne pathogenic Vibrio parahaemolyticus to PAA
      using mutants of peroxide scavenging genes. Among katE1, katE2, katG1, katG2,
      ahpC1 and ahpC2, and their regulator oxyR gene mutants, oxyR and katE mutants
      were highly susceptible to PAA. The growth and lethality of V. parahaemolyticus
      were harmed by 15 ppm of PAA in the ?katE1E2 double mutant, and were
      significantly ameliorated in the presence of the katE1 gene in the wild-type
      strain and the gene-complementary strains that were pre-adapted in 2 ppm of PAA
      or 100 MUM hydrogen peroxide. The application of PAA to these strains induced the
      accumulation of reactive oxygen species. The reduction of the level of hydrogen
      peroxide and gene expression during this treatment was influenced by the presence
      of katE genes. This investigation confirmed the major role of katE1 and a
      compensatory role of katE2 in the resistance of V. parahaemolyticus to PAA, and
      demonstrated some minor differences in the responses of this bacterium against
      PAA and hydrogen peroxide.

PMID- 30099284
TI  - Measuring and modeling interventions in aging.
AB  - Many dietary, pharmaceutical, and genetic interventions have been found to
      increase the lifespan of laboratory animals. Several are now being explored for
      clinical application. To understand the physiologic action and therapeutic
      potential of interventions in aging, researchers must build quantitative models.
      Do interventions delay the onset of aging? Slow it down? Merely ameliorate some
      of its symptoms? If interventions slow some aging mechanisms but accelerate
      others, can we detect or predict the systemic consequences? Statistical and
      analytic models provide a crucial framework in which to answer these questions
      and clarify the systems-level effect of molecular interventions in aging. This
      review provides a brief survey of approaches to modeling lifespan data and places
      them in the context of recent experimental work.

PMID- 30099283
TI  - Lead, cadmium, arsenic, and mercury combined exposure disrupted synaptic
      homeostasis through activating the Snk-SPAR pathway.
AB  - Lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) are among the leading
      toxic agents detected in the environment, and they have also been detected
      simultaneously in blood, serum, and urine samples of the general population.
      Meanwhile early neurologic effects and multiple interactions of Pb, Cd, As, and
      Hg had been found in children from environmentally polluted area. However, the
      current studies of these four metals were mostly limited to the interactions
      between any two metals, whereas the interaction characteristics between any three
      and four metals were rarely studied. In our study, we firstly explored the
      characteristics of the neurotoxic interactions among these four elements in nerve
      cells with factorial designs. The results showed that Pb+Cd+As+Hg co-exposure had
      a synergistic neurotoxic effect that was more severe than that induced by any two
      or three metals, when their individual metals were at human environmental
      exposure (in the blood of U.S. population) relevant levels and below no observed
      adverse effect levels (NOAELs). Therefore, Pb+Cd+As+Hg co-exposure at human
      environmental exposure relevant levels were further selected to examine synaptic
      homeostasis as the cellular and molecular foundation of learning and memory. We
      reported for the first time that Pb+Cd+As+Hg co-exposure induced dose-dependent
      decreases of the dendritic lengths and branching, as well as spine density and
      mature phenotype in primary hippocampal neurons, and the stimulated neurite
      outgrowths in NGF-differentiated PC12 cells. And the above synaptic homeostasis
      disruption was associated with serum induced kinase (Snk)-spine associated Rap
      GTPase activating protein (SPAR) pathway. Our study suggests that human
      environmental Pb, Cd, As, and Hg co-exposure has the potential to evoke
      synergistic neurotoxicity even if their individual metals are below NOAELs, which
      reinforces the need to control and regulate potential sources of metal
      contamination.

PMID- 30099285
TI  - Mindfulness for pregnancy: A randomised controlled study of online mindfulness
      during pregnancy.
AB  - OBJECTIVE: Prenatal depression, stress and anxiety are significant predictors of
      postnatal depression and also have a direct negative impact on the family.
      Helpful psychological interventions during pregnancy are scarce and expensive,
      and usually only available for a small percentage of those suffering or deemed to
      be at risk. The aim of this study was to evaluate the potential of an online
      mindfulness course for expectant mothers. DESIGN: A randomised study was
      conducted to explore differences between control and active participants
      allocated to take an online mindfulness course, offered free to research
      participants, or wait. SETTING: The course provided was online and already
      available but given to study participants for free. Measures were also taken
      online using a secure site to collect the data. PARTICIPANTS: 185 mothers were
      recruited and randomised to the online course (n = 107) or a waitlist control (n
      = 78), with 72 completers at post-course (n = 22 active, n = 50 control) and 48
      completers at postnatal follow-up (n = 16 active and n = 32 control).
      INTERVENTION: The online mindfulness course is available at
      www.bemindfulonline.com and comprises a four-week, condensed version of an eight
      week mindfulness course, with videos and written instructions for guided
      meditation and other mindfulness-based exercises. MEASUREMENTS AND FINDINGS: A
      number of psychological well-being measurements were taken including stress,
      anxiety, depression and pregnancy-specific measure such as labour worry.
      Intention to treat analysis (baseline carried forwards) showed no group
      difference in stress from pre to post intervention or control. KEY CONCLUSIONS:
      Results indicated that the course was potentially beneficial for those who
      completed it, but levels of drop out from the course were very high. IMPLICATIONS
      FOR PRACTICE: Although outcomes for mothers completing the intervention were
      improved relative to a waitlist control, high rates of drop out indicate that the
      online course has low completion rates for pregnant women in its current format.

PMID- 30099286
TI  - Untargeted lipidomics based on UPLC-QTOF-MS/MS and structural characterization
      reveals dramatic compositional changes in serum and renal lipids in mice with
      glyoxylate-induced nephrolithiasis.
AB  - Nephrolithiasis is a systemic metabolic disease with a worldwide incidence that
      is increasing yearly, as well as a high recurrence rate; however, this disease's
      pathogenesis has not been thoroughly elucidated to date. Several epidemiological
      studies have shown that the risk for developing kidney stones increases in people
      with dyslipidemia. To explore the mechanism of lipid-induced kidney stones, we
      established a mouse model for renal urolithiasis based on intraperitoneal
      injections of glyoxylate (120 mg/kg/d). Lipidomics based on ultra high
      performance liquid chromatography coupled with quadrupole-time of flight mass
      spectrometry (UPLC-QTOF-MS/MS) was performed to determine the changes in lipid
      metabolism in serum and kidneys. We screened 179 and 196 different lipid
      metabolites in the kidneys and serum, respectively, including fatty acyls,
      glycerophospholipids, sphingolipids, glycerolipids and prenol lipids. We found
      that polyunsaturated fatty acids, such as arachidonic acid, eicosapentaenoic
      acid, and docosahexoenoic acid, and ceramides and lysophosphocholines mediated
      inflammatory responses and that the oxidative stress induced by oleylethanolamine
      and glycerophosphoethanolamine plasmalogens is closely related to the development
      of kidney stones. These results provide strong evidence for the relationship
      between lipid metabolism and the development of kidney stones and suggest a clear
      direction for future research.

PMID- 30099287
TI  - Heme oxygenase-2 suppresses acute inflammation and improves the survival of skin
      allografts.
AB  - The heme oxygenase (HO) system is an important regulatory arm of the intrinsic
      cytoprotective and anti-inflammatory system. HO-2 plays an important role in
      regulating inflammation following injury. The aim of this study was to evaluate
      the effect of HO-2 overexpression on inflammatory responses. A skin
      transplantation model, involving the application of skin grafts from wild-type or
      HO-2 overexpressing mice to BALB/c mice, was used for investigation. HO-2
      overexpression suppressed the production of pro-inflammatory cytokines (IL-1beta,
      TNF-alpha, and IL-6) in macrophages compared to that in macrophages obtained from
      control mice. HO-2 overexpression also significantly prolonged the survival of
      allografted skin. Our findings suggest that HO-2 attenuates inflammatory
      responses and effectively prolongs skin graft survival.

PMID- 30099288
TI  - Morin attenuates cigarette smoke-induced lung inflammation through inhibition of
      PI3K/AKT/NF-kappaB signaling pathway.
AB  - Cigarette smoke (CS) is a major factor that leads to lung inflammation. The
      prevalence of CS-induced lung injury has continuously increased worldwide. Morin
      exists in a large member of plants and fruits that has been reported to have
      antioxidant and anti-inflammatory properties. In the present study, we tested the
      mechanism and protective effects of morin on CS-induced lung inflammation in
      mice. The mice were exposed to CS for 2 h twice a day for 4 weeks. Morin (10, 20,
      and 40 mg/kg) was treated to mice through oral gavage 1 h before CS
      administration. 24 h after the last CS exposure, the mice were euthanized. The
      lung tissues were collected and the pathological changes, wet/dry ratio, MPO
      activity, MDA levels, and P13K/ATK/NF-kappaB signaling pathway expression were
      detected. The bronchial alveolar lavage fluid (BALF) was obtained and the levels
      of inflammatory cells and inflammatory cytokines were measured. The results
      showed that morin treatment significantly inhibited lung pathological changes,
      wet/dry ratio, MPO activity, and MDA level. The levels of total cells,
      neutrophils, macrophages, as well as the production of inflammatory cytokines in
      the BALF induced by CS were also suppressed by morin. Further research showed
      that morin dramatically suppressed the activation of P13K/ATK/NF-kappaB singling
      pathway induced by CS. This study highlights the protective effects of morin on
      CS-induced lung inflammation, which may, at least part, be mediated through
      inhibiting P13K/ATK/NF-kappaB signaling pathway. These finding demonstrated that
      morin could be a potential drug for CS-induced lung injury.

PMID- 30099289
TI  - Predictors of correspondence between self-reported substance use and urinalysis
      screening among a racially diverse cohort of young men who have sex with men and
      transgender women.
AB  - It is unknown if estimates of illicit drug use among young men who have sex with
      men and transgender women (YMSM/TW) may be biased due to historical distrust of
      research or reliable due to more accepting norms for use. Research is needed to
      examine the validity of drug use self-reports among YMSM/TW. Data came from an
      ongoing longitudinal study of YMSM/TW aged 16-29 living in Chicago (analytic N =
      1029). Baseline urinalysis screens for marijuana, ecstasy, amphetamine,
      methamphetamine, cocaine, benzodiazepine, and opiate metabolites were compared to
      self-reported use within different recall periods using measures of concordance.
      Generalized estimating equations logistic regressions were conducted on three
      waves of data to identify predictors of disclosing past-6-month use of marijuana
      and non-marijuana drugs. Past-6-month self-reported use of all non-marijuana
      substances was <15%. There was excellent agreement between self-reported and drug
      tested marijuana use. For other substances, sensitivities within the urinalysis
      detection window were <0.5 but increased with longer recall periods. Black
      participants had lower odds of disclosing non-marijuana drug use. Gender minority
      participants had lower odds of disclosing marijuana use. Participants with a
      history of arrest had higher odds of disclosing both marijuana and non-marijuana
      drug use. Wave and year of first research participation were non-significant,
      suggesting no systematic bias or increasing honesty associated with longer
      research participation. Programs that rely on self-identification of non
      marijuana illicit substance use may be missing a substantial portion of drug
      using YMSM/TW. Future epidemiological studies should work to reduce social
      desirability biases and include biomarker-based drug screenings to increase
      validity.

PMID- 30099290
TI  - Comparison of catalytically non-productive adsorption of fungal proteins to
      lignins and pseudo-lignin using isobaric mass tagging.
AB  - Catalytically non-productive adsorption of fungal enzymes to pseudo-lignin (PL)
      was compared to adsorption to lignin preparations derived from different sources
      (SL, spruce; BL, birch; OL, beech) using different methods [steam
      pretreatment/enzymatic saccharification (SL, BL) and organosolv processing (OL)].
      The protein adsorption to the SL was more extensive than the adsorption to the
      hardwood lignins, which was relatively similar to the adsorption to the PL. The
      adsorption patterns of 13 individual proteins were studied using isobaric mass
      tagging with TMTsixplex reagent and LC-MS/MS analysis. The results suggest that,
      on an average, adsorption of proteins equipped with carbohydrate-binding modules,
      such as the cellulases CBHI, EGII, and EGIV, was less dependent on the quality of
      the lignin/PL than adsorption of other proteins, such as beta-Xyl, Xyn-1, and Xyn
      2, which are involved in xylan degradation.

PMID- 30099291
TI  - Effects of dibutyl phthalate and di(2-ethylhexyl) phthalate with their
      metabolites on CYP2C9*1 and CYP2C19*1 activities in vitro.
AB  - The aim of this article is to assess the effect of phthalates on the activities
      of CYP2C9 and CYP2C19 in vitro. In this study, recombinant CYP2C9*1 and CYP2C19*1
      microsomes were used to investigate the effects of phthalates and their
      metabolites on corresponding enzyme activities in vitro. 2-100 MUM substrate of
      enzyme was incubated with series concentration of phthalates for 30 min at 37 
      degrees C. The metabolic products were detected using ultra-high performance
      liquid chromatography (UHPLC) and ultra-high performance liquid chromatography
      mass spectrometry (UHPLC-MS/MS) methods. The results showed dibutyl phthalate
      (DBP) significantly inhibited CYP2C9*1 with an activity inhibition rate of 67.3%
      and half-maximal inhibitory concentration (IC50) of 29.63 MUmol L-1, but its
      metabolite monobutyl phthalate (MBP) had no significant effect. On the other
      hand, di(2-ethylhexyl)phthalate (DEHP) had no effect on CYP2C9*1, but its
      metabolite monoethylhexyl phthalate (MEHP) significantly inhibited the enzyme
      activity with an activity inhibition rate of 90.6% and IC50 of 6.37 MUmol L-1.
      With regards to CYP2C19*1, DBP completely inhibited the enzyme activity with an
      activity inhibition rate of 100% and IC50 of 2.63 MUmol L-1, but its metabolite
      MBP had no effect on it. DEHP and MEHP also inhibited the activity of CYP2C19*1.
      Further investigation showed MEHP was a competitive inhibitor of CYP2C9*1 (Ki =
      7.063 MUmol L-1), and DBP was a competitive inhibitor of CYP2C19*1 (Ki = 7.013
      MUmol L-1) against their substrates, both phthalates were non-competitive
      inhibitors of the cofactor NADPH. Our results suggested that DBP, DEHP, and their
      metabolites exhibited significant inhibitory effects toward either CYP2C9*1 or
      CYP2C19*1. These findings provided valuable information for a potentially toxic
      mechanism of DEHP and DBP on endocrine disruption and a useful guidance for safe
      and effective usage of drugs in patients with long-term DEHP and DBP exposure.

PMID- 30099292
TI  - In-vitro metabolism, CYP profiling and metabolite identification of E- and Z-
      guggulsterone, a potent hypolipidmic agent.
AB  - The polyphenol E- and Z-gugggulsterone (GS) is an antagonist ligand for the
      Farnesoid X Receptor (FXR) and known to possess potent hypolipidemic properties
      as shown in various preclinical and clinical studies. In the present study, we
      examined drug-like properties of GS by assessing the isomers plasma protein
      binding, metabolic stability, CYP profiling, CYP inhibition, and phase I and II
      metabolite identification of GS using liver microsomes and S9 fractions. GS
      followed Lipinski and Veber rules and were substrates of CYP3A CYP2C19 and CYP2D6
      isoforms. GS was also found to be an inhibitor of CYP2C19 with an IC50 value of
      2.1 MUM. GS showed high plasma protein binding (<96%), and low to moderate
      binding with human serum albumin (~70%). Unbound intrinsic clearances (CLint, in
      vitro) was determined to be low at 0.029 +/- 0.0009 and 0.027 +/- 0.008 mL/min/mg
      protein for E- and Z-isomer, respectively in human liver microsomes. Nineteen
      phase I and II metabolites were identified and hydroxylation was found to be
      major metabolic pathway using human liver microsomes and S9 fractions. The
      results of in-vitro drug-metabolism studies provide impetus for further
      structural modification of this pharmacophore in order to improve the stability
      of drugs with potent hypolipidemic effects.

PMID- 30099293
TI  - Characterization of polydisperse macrogols and macrogol-based excipients via HPLC
      and charged aerosol detection.
AB  - Macrogol-based emulsifiers and their respective precursor substances, i.e.
      macrogols (PEG), fatty acids (FA), and fatty alcohols (FAA), are widely used
      excipients which are usually characterized by a series of tests described within
      the European Pharmacopoeia (Ph. Eur.). Examples are bulk parameters such as the
      hydroxyl value, the peroxide value, and the determination of fatty acids
      composition by gas chromatography. The choice of tests depends on the emulsifier
      considered and its possible precursors. Though all methods are well established,
      most of them are time consuming and, in some cases, prone to errors and exhibit a
      low reproducibility. Here, an alternative and supplemental method was developed,
      using a HPLC-system coupled to a charged aerosol detector (CAD). Seven PEG
      samples, five saturated as well as two nonsaturated FA samples, and two FAA
      samples were analyzed. Together with these precursors, 13 macrogol-based
      emulsifiers of 3 different groups, i.e. macrogol ethers with FAA, macrogol esters
      with FA, and polysorbates, were successfully analyzed for oligomeric distribution
      and free precursor molecules in one run.

PMID- 30099294
TI  - Immobilized enzyme-based analytical tools in the -omics era: Recent advances.
AB  - Protein analysis is a field under rapid development mainly thanks to
      technological advances which have granted miniaturization of analytical devices,
      automation and higher detection sensitivity. The interest in the field has
      paralleled the expansion of the -omics era, laying down the bases for the current
      applications in proteomics and glycomics. Advances in protein sample
      transformation prior to analysis have led to reduction of sample consumption and
      contamination, enhancing throughput. Within this context, and thanks to the
      availability of new high performing materials and technologies, increasingly more
      efficient and miniaturized enzyme-based analytical tools have been proposed to
      overcome shortcomings encountered in the in-solution enzymatic reactions (protein
      digestion and protein deglycosylation, for proteomics and glycomics,
      respectively). In this context, immobilized enzyme reactors (IMERs) and IMER
      based platforms have been developed as promising approaches toward automation and
      higher analysis throughput. The scenario is in continuous development as
      underlined by thirty-four papers published in the last five years. This review
      encompasses recent advances in the design and operational set-ups of IMERs
      purposely developed for the analysis of proteins and glycoproteins. Recently
      developed dual IMERs, which integrate more than one processing step into a single
      IMER, and analytical platforms exploiting tandem IMERs are also reviewed and
      commented.

PMID- 30099296
TI  - Construction of Ag-incorporated coating on Ti substrates for inhibited bacterial
      growth and enhanced osteoblast response.
AB  - In orthopedic fields, effective anti-infection property and promotive
      biocompatibility on surface of titanium implants are two crucial factors for long
      term successful implants. Herein, Ag nanoparticles (NPs) loaded TiO2 nanotubes
      (TNT) arrays were fabricated on Ti substrates with assistance of ultraviolet
      irradiation. Then, bioactive multilayer films of chitosan (CHI) and dialdehyde
      alginate (ADA) pair were deposited onto the Ag-loaded TNT arrays via a layer-by
      layer (LBL) self-assembly technique, which could effectively achieve the
      impactful antibacterial ability of titanium and endow the substrates with
      favorable biocompatibility. The driving force of the assembling of multilayer
      films came from two sources, electrostatic interaction and covalent interaction
      of Schiff-bonds between CHI and ADA. The surface topography and wettability of
      different samples were characterized by field emission scanning electron
      microscopy, transmission electron microscopy and contact angle measurements,
      respectively. In addition, Ag ions release from TNT-Ag and LBL substrate was
      measured via inductively coupled plasma atomic emission spectroscopy (ICP-AES).
      The results of a series of biological behaviors of osteoblasts on different
      substrates in vitro, including lactate dehydrogenase activity assay, cytoskeleton
      observation and cell viability measurement, confirmed that LBL substrates coated
      with (ADA-CHI)10 multilayer films have negligible cytotoxicity and promote
      osteoblast growth compared with TNT-Ag substrates, which could ascribe to the
      slow-release of Ag ions and the biocompatibility of (ADA-CHI)10 multilayer. More
      importantly, owing to the release of Ag ions, the LBL samples still exhibited a
      prominent antibacterial activity for S.aureus and E.coli. Characteristics of
      bacterial adhesion and viability measurement proved that the fabricated Ag
      incorporated platform was capable of obviously inhibiting the adhesion and growth
      of bacteria. Therefore, this approach of surface modification for Ti substrates
      presented here may provide an alternative strategy to simultaneously meet the
      desirable osteoblast growth and reduce bacterial infection for implants in
      clinical application.

PMID- 30099297
TI  - Autophagy induced by cardamonin is associated with mTORC1 inhibition in SKOV3
      cells.
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) integrates energy level to
      modulate cell proliferation and autophagy. Cardamonin exhibits anti-proliferative
      activity through inhibiting mTOR. In this study, the effect of cardamonin on
      autophagy and its mechanism on mTOR inhibition were investigated. METHODS: Cell
      viability and proliferation were measured by MTT assay and BrdU incorporation,
      respectively. Cell apoptosis was assayed by flow cytometry and cell autophagy was
      detected by electron microscopy and GFP-LC3 fluorescence. The mechanism of
      cardamonin on mTORC1 inhibition was investigated by Raptor siRNA and Raptor over
      expression. RESULTS: The cell viability and proliferation were inhibited by
      cardamonin. The autophagosomes and the protein level of LC3-II were increased by
      cardamonin. Cell apoptosis and the levels of cleaved PARP and Caspase-3 were
      increased by cardamonin. Cardamonin inhibited the phosphorylation of mTOR and
      ribosome S6 protein kinase 1 (S6K1) as well as the protein level of regulatory
      associated protein of mTOR (Raptor). However, cardamonin had no effect on the
      component of mTORC2 and its downstream substrate Akt. The inhibitory effect of
      cardamonin on the phosphorylation of mTOR and S6K1 was eliminated by Raptor
      knockdown with siRNA, whereas this effect of cardamonin was stronger than that of
      rapamycin and AZD8055 in Raptor over-expression cells. Cell viability was
      inhibited by cardamonin in both Raptor knockdown and Raptor over-expression
      cells, which was consistent with the inhibitory effect of cardamonin on mTOR.
      CONCLUSION: These findings demonstrated that the autophagy induced by cardamonin
      was associated with mTORC1 inhibition through decreasing the protein level of
      Raptor in SKOV3 cells.

PMID- 30099298
TI  - Nephroprotective effects of nebivolol in 2K1C rats through regulation of the
      kidney ROS-ADMA-NO pathway.
AB  - BACKGROUND: To evaluate the protective effect of nebivolol against kidney damage
      and elucidate the underlying mechanism in a two-kidney, one-clip (2K1C) rat
      model. METHODS: 2K1C rats were obtained by clipping left renal artery of male
      Wistar rats and were considered hypertensive when systolic blood pressure (SBP)
      was >=160mmHg 4 weeks after surgery. The 2K1C hypertensive rats were divided into
      untreated, nebivolol (10mg/kg, ig), and atenolol (80mg/kg, ig) treatment groups.
      The treatments lasted for 8 weeks. SBP, kidney structure and function, plasma and
      kidney angiotensin (Ang) II, nitric oxide (NO), asymmetric dimethylarginine
      (ADMA), and the oxidant status were examined. Kidney protein expression of NADPH
      oxidase (Nox) isoforms and its subunit p22phox, nitric oxide synthase (NOS)
      isoforms, protein arginine N-methyltransferase (PRMT) 1, and dimethylarginine
      dimethylaminohydrolase (DDAH) 1 and 2 was tested by western blotting. RESULTS:
      Nebivolol and atenolol exerted similar hypotensive effects. However, atenolol had
      little effect while nebivolol significantly ameliorated the functional decline
      and structural damage in the kidney, especially in non-clipped kidney (NCK),
      which was associated with the reduction of Ang II in NCK. Moreover, nebivolol
      inhibited the NCK production of reactive oxygen species (ROS) by decreasing Nox2,
      Nox4, and p22phox expression. Further, nebivolol reduced the plasma and kidney
      ADMA levels by increasing DDAH2 expression and decreasing PRMT1 expression.
      Nebivolol also increased the NCK NO level by ameliorating the expression of
      kidney NOS isoforms. CONCLUSIONS: Our results demonstrated that long-term
      treatment with nebivolol had renoprotective effect in 2K1C rats partly via
      regulation of kidney ROS-ADMA-NO pathway.

PMID- 30099299
TI  - Anti-melanogenesis effect of dehydroglyasperin C through the downregulation of
      MITF via the reduction of intracellular cAMP and acceleration of ERK activation
      in B16F1 melanoma cells.
AB  - BACKGROUND: In mammals, UV radiation induces melanin synthesis in melanocyte for
      protecting their skin through the stimulation of alpha-melanocyte stimulating
      hormone (alpha-MSH) from keratinocytes. In this study, the inhibitory effects of
      dehydroglyasperin C (DGC), an useful component of Glycyrrhiza uralensis (G.
      uralensis), was investigated on melanogenesis induced by alpha-melanocyte
      stimulating hormone (alpha-MSH) and its mechanisms. METHODS: Melanogenesis
      suppression effect of DGC on alpha-MSH induced B16F1 melanoma cells. The cell
      viability was measured by MTT assay. Expression and phosphorylation of melanogeic
      protein were conducted using western blot. cAMP acceleration was measured by cAMP
      immunoassay kit. To investigate whitening mechanism, we used ERK inhibitor
      (PD98059). RESULTS: DGC decreased intra cellular tyrosinase (TYR) activity and
      expression of melanin synthesis related proteins (TYR and TRP-1) in a dose
      dependent manner on alpha-MSH induced melanogenesis. In addition, DGC induced the
      downregulation of MITF (melanocyte-specific transcription factor) through
      suppression of cAMP-CREB pathway. Also, phosphorylation of extracellular signal
      regulated kinase (ERK) decreased MITF by DGC treatment. CONCLUSION: Therefore,
      DGC could be used as a whitening ingredient in skin and clinical usage against
      hyperpigmentation.

PMID- 30099300
TI  - Limitations on using CDOM as a proxy for DOC in temperate lakes.
AB  - Colored dissolved organic matter (CDOM) has been widely studied as part of
      efforts to improve understanding of the aquatic carbon cycle, by laboratory, in
      situ, and remote sensing methods. We studied ecoregion-scale differences in CDOM
      and dissolved organic carbon (DOC) to understand variability in organic matter
      composition and the use of CDOM as a proxy for DOC. Data from 299 lakes across
      the U.S. Upper Midwest showed that CDOM, measured as absorptivity at 440 nm
      (a440), correlated strongly with DOC (R2 = 0.81, n = 412). Colored lakes in the
      Northern Lakes and Forests (NLF) ecoregion drove this relationship. Lakes in the
      North Central Hardwood Forests (NCHF) had low color (most had a440 < 3 m-1) and
      weaker CDOM-DOC relationships (R2 = 0.47). Spectral slopes and specific
      ultraviolet absorbance (SUVA), indicated relatively low aromaticity and non
      terrestrial DOM sources in low color lakes. Multiple regression analyses that
      included total dissolved nitrogen (TDN) and CDOM, but not chlorophyll a, improved
      DOC estimates in low color lakes, suggesting a dominant contribution of non
      planktonic sources of low color DOM in these lakes. Our results show that CDOM is
      a reliable, regional proxy for DOC in lakes where forests and wetlands dominate
      the landscape and the DOM is primarily terrestrial in origin. Mapping of lake DOC
      at broad spatial scales by satellite-derived CDOM has lower accuracy in low color
      lakes.

PMID- 30099302
TI  - Non-coding genetic variation shaping mental health.
AB  - Over 98% of our genome is non-coding and is now recognised to have a major role
      in orchestrating the tissue specific and stimulus inducible gene expression
      pattern which underpins our wellbeing and mental health. The non-coding genome
      responds functionally to our environment at all levels, encompassing the span
      from psychological to physiological challenge. The gene expression pattern,
      termed the transcriptome, ultimately gives us our neurochemistry. Therefore a
      major modulator of mental wellbeing is how our genes are regulated in response to
      life experiences. Superimposed on the aforementioned non-coding DNA framework is
      a vast body of genetic variation in the elements that control response to
      challenges. These differences, termed polymorphisms, allow for a differential
      response from a specific DNA element to the same challenge thus potentially
      allowing 'individuality' in the modulation of our transcriptome. This review will
      focus on a fundamental mechanism defining our psychological and psychiatric
      wellbeing, namely how genetic variation can be correlated with differential gene
      expression in response to specific challenges, thus resulting in altered
      neurochemistry which consequently may shape behaviour.

PMID- 30099301
TI  - System-level model and experiments for irrigation water alkalinity reduction and
      enrichment using an atmospheric pressure dielectric barrier discharge.
AB  - The treatment of distilled water with varying amounts of dissolved sodium
      bicarbonate (representing alkalinity) is considered using an atmospheric pressure
      electrical discharge. The discharge ignited between a capillary tube (used as
      powered electrode) and a ground electrode wrapped around the beaker holding the
      treated water consists of streamers propagating in ambient air and striking the
      water surface. The streamer interaction with water is shown to lead to a decrease
      in pH and an increase in nitrate concentration. The pH variation with time is
      shown to be similar to a titration curve for acid-base neutralization with final
      pH values around 3 for 22 min of treatment. The nitrate ion concentration
      increase with time is consistent with a two-rate system-level model that is
      characterized by two asymptotic rates for NO3- creation by the plasma. The two
      asymptotic rates are calibrated to be about 2.7 MUmol/min and 22.5 MUmol/min with
      the transition between the two rates occurring at the breakeven time that is
      representative of the time required for all dissolved bicarbonate to be consumed
      by the plasma treatment. The increase in rate of NO3- creation at the breakeven
      time is attributed to the increase in conductivity of the treated solution once
      all bicarbonate is consumed thereby modifying the plasma properties. Another
      system-level model that is based on the observed pH variation is also considered
      for comparison with measured data. While both system-level models have some
      discrepancies with the measurements, the two-rate model based on the nitrate ion
      concentration is concluded to be more useful for determining the NO3- formation
      rates in the context of irrigation water enrichment. The discrepancies are
      attributed to the simplicity of the system-level models considered here where the
      effect of the plasma is completely represented by the creation of just one
      chemical species in HNO3 thereby neglecting potentially important species such as
      HNO2 and H2O2. Nevertheless, the proposed system-level model could greatly assist
      in the design of plasma treatment systems with specified alkalinity, pH and
      nitrate ion levels for irrigation water.

PMID- 30099303
TI  - Three dimensional vanadium pentoxide/graphene foam composite as positive
      electrode for high performance asymmetric electrochemical supercapacitor.
AB  - The electrochemical performance of hydrothermal synthesized three dimensional
      (3D) orthorhombic vanadium pentoxide (V2O5) nanosheets and vanadium
      pentoxide/graphene foam (V2O5/GF) composites at different mass loading of GF were
      successfully studied. The optimized V2O5/GF-150 mg composite provided a high
      specific capacity of 73 mA h g-1, which was much higher than that the pristine
      V2O5 (60 mA h g-1) nanosheets at a specific current of 1 A g-1. A hybrid
      capacitor was also fabricated by adopting a carbon-based negative electrode
      obtained from the pyrolysis of an iron-PANI polymer (C-Fe/PANI) mixture and the
      3D V2O5/GF-150 mg composite as the positive electrode in 6 M KOH electrolyte. The
      hybrid device of V2O5/GF-150 mg//C-Fe/PANI demonstrated a high energy density of
      39 W h kg-1 with a corresponding high power density of 947 W kg-1 at a specific
      current of 1 A g-1 in an operating voltage window of 0.0-1.6 V. The hybrid device
      also exhibited an excellent cycling stability with 74% capacity retention
      recorded for up to 10,000 constant charging-discharge cycles and an excellent
      ageing test at a specific current of 10 A g-1.

PMID- 30099304
TI  - Metal organic frameworks derived cobalt sulfide/reduced graphene oxide composites
      with fast reaction kinetic and excellent structural stability for sodium storage.
AB  - We report a metal-organic framework-derived Co9S8 nanoflakes on reduced graphene
      oxide sheet composites as an advanced sodium-ion battery anode. Using a
      galvanostatic intermittent titration technique, we reveal that the sodium
      diffusion coefficient of the composite is higher than that of its counterpart. Ex
      situ scanning electron microscopy images suggest the excellent mechanical
      stability of Co9S8 nanoflakes on the reduced graphene oxide sheet electrode
      during cycling, thereby facilitating cyclic stability. The partial surface
      induced capacitive effect also contributes to electrochemical performance. With
      the reduced graphene oxide, the Co9S8 nanoflakes on the reduced graphene oxide
      sheet electrode deliver a high discharge capacity of 551 mA h g-1 at 0.1 A g-1, a
      good rate capability at 10 A g-1, and an excellent cyclic stability up to 500
      cycles. rGO/Co9S8 shows potential for practical applications in
      Na3V2(PO4)3||rGO/Co9S8 full cells.

PMID- 30099305
TI  - Elimination of bromate from water using aluminum beverage cans via catalytic
      reduction and adsorption.
AB  - While zero valent aluminum (ZVAl) is a promising reductant for eliminating
      bromate from water, ZVAl is typically obtained from reagent grade aluminum. As
      used aluminum beverage can is the most common aluminum waste, it can be
      conveniently used to prepare ZVAl. Thus, in this study aluminum beverage cans are
      employed for the first time as a plentiful and easily accessible aluminum source
      to afford ZVAl for eliminating bromate from water. As aluminum is easily oxidized
      to form aluminum oxide, aluminum can pieces (ACPs) are pre-treated with HCl for
      removing the oxide layer to afford ZVAl. While non-acid-treated ACP is
      ineffective to remove bromate, the acid-treated ACP successfully eliminates
      bromate from water completely. Bromate elimination by ACP is attributed to
      reduction of bromate to bromide by the reactive sites of ACP and adsorption of
      bromate to the surface of ACP. Bromate elimination by ACP also proceeds much
      faster at higher temperatures and low pH values, while the alkaline condition
      causes serious negative effects on bromate elimination. Besides, oxalic acid is
      found to facilitate bromate elimination not only on the kinetics but also
      reduction to bromide because the passivation layer is suppressed in the presence
      of oxalic acid. ACP could also be reused and the acid-washing regeneration could
      enable used ACP to restore its reactive sites for bromate elimination. This study
      successfully demonstrates the valorization of aluminum beverage cans for
      mitigating the toxic bromate and the findings here provide useful information and
      insights to develop aluminum beverage cans for controlling pollutants in water.

PMID- 30099306
TI  - Cost-effective synthesis and superior electrochemical performance of sodium
      vanadium fluorophosphate nanoparticles encapsulated in conductive graphene
      network as high-voltage cathode for sodium-ion batteries.
AB  - Sodium vanadium fluorophosphate (Na3(VO)2(PO4)2F, denoted as NVPF) has attracted
      particular interests as cathode for high-energy sodium-ion batteries (SIBs) owing
      to the high working potential, high specific capacity, and robust structural
      framework. However, it is challenged by the low electron conductivity and lack of
      available facile synthesis method. Herein, an environmentally benign, cost
      effective synthesis route is reported to produce NVPF nanoparticles encapsulated
      in conductive graphene network (NVPF/C), involving low-temperature synthesis of
      NVPF nanoparticles in absolute aqueous solvents and subsequent construction of
      conductive network through thermally induced transformation of graphene-oxide
      nanosheets. The resultant product is structurally and electrochemically
      investigated by combining X-ray diffraction, fourier transform infrared
      spectroscopy, scanning electron microscope, transition electron microscope, and
      electrochemical analysis. Experimental results show that the optimized NVPF/C
      product possesses a three-dimensional graphene-encapsulation nanostructure
      composed of ~100 nm NVPF nanoparticles and ~4 nm carbon-coating layer. The unique
      hierarchical structure enables it cycling with excellent electrochemical
      performance in terms of a high reversible capacity (116.4 mA h g-1 at 0.2 C),
      excellent high-rate capability (87.4 mA h g-1 at 10 C) and long-term lifetime
      (82.1% capacity retention after 1200 cycles). It is indicated that the facile
      synthesis route can achieve high-performance NVPF/C material for SIBs.

PMID- 30099307
TI  - Fabrication and adsorption performance for CO2 capture of advanced nanoporous
      microspheres enriched with amino acids.
AB  - Advanced porous organic materials with high gas storage capacity and high
      selectivity have been rapidly developed for CO2 adsorbents in the recent decade,
      due to extremely high surface area and nanoscale pore size. Here, novel amino
      acids-incorporated solid adsorbents based on porous hypercrosslinked polymers
      were fabricated by a dispersion polymerization of an aromatic monomer and
      quaternary ammonium salt comonomer, subsequently a hypercrosslinked reaction and
      an ion-exchange step. The developed adsorbents presented mesopores structure with
      BET surface area up to 864 m2/g and an extremely high CO2 capturing capacity up
      to 60.7 wt% (13.8 mmol/g) at 273 K/1 bar. The results also showed the adsorbent
      had an excellent recycling ability over repetitive adsorption-desorption cycles.
      All the results suggest that the amino acids-modified porous sorbents are
      promising CO2 sorbents that can meet the challenges of the current CO2 capture
      and storage technology.

PMID- 30099308
TI  - Plasmonic assemblies of gold nanorods on nanoscale patterns of poly(ethylene
      glycol): Application in surface-enhanced Raman spectroscopy.
AB  - Approaches are needed for the tailored assembly of plasmonic building blocks on
      the surface of substrates to synergistically enhance their properties. Here we
      demonstrate selective immobilization and assembly of gold nanorods (NRs) on
      substrates modified and patterned with end-grafted poly(ethylene glycol) (PEG)
      layers. The ligand exchange from the initial cetyltrimethylammonium bromide to
      sodium citrate was necessary for the immobilization of gold NRs onto PEG grafted
      substrates. Linear nanopatterns of PEG were fabricated using electrospun
      nanofibers as masks in oxygen plasma etching. The selective immobilization of
      citrate-stabilized gold NRs with a length of ~50 nm and a width of 20 nm on the
      nanopatterned PEG layers led to linear and registered arrays of rods. The number
      of gold NRs per line depended on the width of the patterns and approached 1 when
      the width of the patterns was comparable to the length of the rods. The
      confinement of the binding regions led to a ~3 fold increase in the number of
      gold NRs immobilized per unit area. The selective and dense immobilization of
      gold NRs on the nanoscale patterns of PEG resulted in spatially defined and
      strong surface-enhanced Raman scattering activity enabling detection of molecules
      at concentrations as low as 1 nM.

PMID- 30099309
TI  - Multifunctional Ag nanoparticle decorated Si nanowires for sensing,
      photocatalysis and light emission applications.
AB  - We report on the fabrication of Ag nanoparticle (NP) decorated mesoporous Si
      nanowire (NW) heterostructure (HS) by a simple and low cost chemical process. The
      as-grown Si NWs are mesoporous in nature and the Ag NP decorated Si NWs (Ag@Si
      NWs) exhibit broadband light emission, ultralow reflectance, efficient
      photocatalytic degradation of organic dyes and excellent sensitivity for the
      detection of organic molecules over a wide range of concentration. The broadband
      white light photoluminescence emission from the bare Si NWs is explained on the
      basis of quantum confinement effect in Si NCs/NWs and the nonbridging oxygen hole
      center defects in the SiSiOx interface. High work function of the noble metal NPs
      facilitates the effective separation of the photoinduced electron-hole pairs in
      Si NWs, which enables the Ag@Si NWs to exhibit high photocatalytic efficiency for
      the degradation of organic dye. The Ag@Si NWs exhibited high potential and
      sensitivity for the selective and quantitative detection of different organic
      molecules at extremely low concentration down to 10-12 M by surface-enhanced
      Raman scattering and 10-11 M by fluorescence-based detection. These versatile
      properties of the Ag@Si NWs open up opportunities for a variety of energy and
      environmental applications, such as white light emission, solar cell, artificial
      photosynthesis, disposal of organic pollutant and bio-chemical sensors etc.

PMID- 30099310
TI  - Computational study on the mechanisms and kinetics of the CH2 = CHCH2F with O(3P)
      reaction.
AB  - The potential energy surface for the reaction of O(3P) with CH2 = CHCH2F has been
      studied at the CCSD(T)//M06-2X level of theory. Three different reaction
      entrances were revealed, namely, terminal-C addition, central-C addition, and
      H(or F)-abstraction, leading to CH2OCHCH2F (IM1), CH2CHOCH2F (IM2) and HO + C3H4I
      (OF + C3H5), respectively. The corresponding activation barriers are 3.04 (TS1),
      3.71 (TS2), 7.06 (h-TS1), 12.68 (h-TS2), 14.04 (h-TS3) and 63.58 kcal/mol (F-TS1)
      kcal/mol. Several conceivable decomposition and isomerization channels were also
      examined for IM1 and IM2. The total and individual rate constants were calculated
      by using Multichannel RRKM and TST theory over a wide range of temperatures (200
      3000 K) and pressures(10-14-1014 Torr).The branching ratios indicate that IM1 is
      the major product at 200-800 K. The production of P1 (CH2FCHCHO + H)via H
      elimination from IM1 becomes dominant at high temperatures.

PMID- 30099311
TI  - Nonlinear least squares with local polynomial interpolation for quantitative
      analysis of IR spectra.
AB  - When using spectroscopic instrumentation for quantitative analysis of mixture,
      spectral intensity non-linearity and peak shift make it challenging for building
      calibration model. In this study, we investigated the performance of a nonlinear
      model, namely nonlinear least squares with local polynomial interpolation
      (NLSLPI). In NLSLPI, the parameters to be optimized are the concentrations of the
      components. Levenberg-Marquardt (L-M) method is used to solve the nonlinear-least
      squares optimization problem and local polynomial interpolation is used to
      generate the nonlinear function for each component. We tested the robustness of
      NLSLPI on a computer-simulation dataset. We also compared NLSLPI, in terms of
      RMSEP, to partial least squares (PLS), classical least squares (CLS) and
      piecewise classical least squares (PCLS) on a real-world dataset. Experimental
      results demonstrate the effectiveness of the proposed method.

PMID- 30099312
TI  - Spectrofluorometric genotyping of single nucleotide polymorphisms using carbon
      dots as fluorophores.
AB  - In the present manuscript, a new spectrofluorometric method for the genotyping of
      various single nucleotide polymorphisms (SNPs) using carbon dots (CDs) is
      investigated. For the construction of the assay, thiolated probe DNA is self
      assembled on a gold surface via sulfur-gold chemistry and afterward, the probe is
      partially hybridized with a longer target DNA strand. Subsequently, the
      unhybridized section of the target DNA is hybridized with a capture DNA to form
      the DNA double-helix self-assembled monolayer on the gold surface. Finally, CDs
      surface amine groups are covalently attached to the 5' phosphate groups of
      various monobases (MB-CDs) using phosphoramidite chemistry. In this method,
      genotyping of SNPs is based on following the changes in fluorescence intensity of
      the MB-CDs suspensions before and after incubation with DNA modified gold
      surface. The assay is straightforward with no need for target labeling and is
      sensitive and low cost enough to genotype various SNPs independent of their
      position in a DNA double helix with an acceptable limit of detections in
      picomolar ranges.

PMID- 30099313
TI  - Comment on the frequently used method of the metal complex-DNA binding constant
      determination from UV-Vis data.
AB  - Present contribution describes the UV-Vis study of the mixture of Cu(II) ions,
      pyridoxal 5'-phosphate nicotinoyl hydrazone and DNA. Neither free hydrazone nor
      its copper(II) complex interacts with DNA under the given concentration
      conditions. The changes in the UV-Vis spectra of the mixture containing metal
      complex and DNA are caused by partial dissociation of the coordination compound
      and complexation of the released Cu(II) ions with DNA. This result was obtained
      by the analysis of a number of the reactions that could occur in the solution of
      Cu(II) ions, buffer components (namely, Tris), ligand (hydrazone), and DNA.

PMID- 30099314
TI  - Application of terahertz spectroscopy and chemometrics for discrimination of
      transgenic camellia oil.
AB  - Discrimination of transgenic edible oil has become the focus of attention in the
      field of food safety. In this paper, we propose a method for discrimination of
      transgenic edible oils by using terahertz spectroscopy combine with weighted
      linear discriminant analysis (WLDA). To evaluate the lustiness of the model, we
      employ successive projection arithmetic (SPA) and partial least squares (PLS) to
      verify the discrimination performance through variable selection. The results
      demonstrate that the SPA-WLDA model has higher classification accuracy than PLS
      WLDA. In conclusion, terahertz spectroscopy is coupled with chemometrics is an
      effective method for discriminating various types of transgenic edible oils.

PMID- 30099315
TI  - Carbon quantum dots embedded mesoporous silica for rapid fluorescent detection of
      acidic gas.
AB  - A fluorescent composite consisting of an ordered mesoporous material (MCM-41) and
      carbon quantum dots (CQDs) was successfully prepared and designated as MCM/CQDs.
      CQDs with citric acid as a carbon source and diethylenetriamine as a nitrogen
      doping agent were directly synthesized in MCM-41 via a hydrothermal method and
      the reaction conditions were optimized. The MCM/CQDs prepared at the optimized
      condition showed different fluorescent properties (as indicated by the
      fluorescent emission wavelength and fluorescent response to acid) compared to the
      CQDs formed in water. It was found that the preparation of MCM/CQDs caused
      changes in the characteristics (i.e., surface and pore properties) of MCM-41,
      which in turn could impact the formation of CQDs in MCM-41. The prepared MCM/CQDs
      combined the porous nature of MCM-41 and the fluorescent properties of CQDs, and
      can be applied to the rapid detection of acetic acid (HAc) as a model organic
      volatile compound. The detection was more sensitive for HAc gas (detection limit:
      0.2 MUmol/L) than for HAc solution (detection limit: 3 MUmol/L). The reason was
      explained by the physical adsorption of HAc gas by MCM-41, which increased the
      HAc concentration in the MCM/CQDs and therefore enhanced the fluorescent
      response. This study expanded the potential application of CQDs embedded
      mesoporous silica in gas sensing, especially in the rapid and sensitive detection
      of acetic acid as a representative of acidic volatile compounds.

PMID- 30099316
TI  - Facilitated delignification in CAD deficient transgenic poplar studied by
      confocal Raman spectroscopy imaging.
AB  - Lignocellulosic biomass represents the only renewable carbon resource which is
      available in sufficient amounts to be considered as an alternative for our fossil
      based carbon economy. However, an efficient biochemical conversion of
      lignocellulosic feedstocks is hindered by the natural recalcitrance of the
      biomass as a result of a dense network of cellulose, hemicelluloses, and lignin.
      These polymeric interconnections make a pretreatment of the biomass necessary in
      order to enhance the susceptibility of the polysaccharides. Here, we report on a
      detailed analysis of the favourable influence of genetic engineering for two
      common delignification protocols for lignocellulosic biomass, namely acidic
      bleaching and soda pulping, on the example of CAD deficient poplar. The altered
      lignin structure of the transgenic poplar results in a significantly accelerated
      and more complete lignin removal at lower temperatures and shorter reaction times
      compared to wildtype poplar. To monitor the induced chemical and structural
      alterations at the tissue level, confocal Raman spectroscopy imaging, FT-IR
      spectroscopy, and X-ray diffraction were used.

PMID- 30099318
TI  - The effect of movement-focused and breath-focused yoga practice on stress
      parameters and sustained attention: A randomized controlled pilot study.
AB  - Yoga-based practices (YBP) typically involve a combination of movement sequences,
      conscious regulation of the breath, and techniques to engage attention. However,
      little is known about whether effects of YBP result from the synergistic
      combination of these components, or whether a subset may yield similar effects.
      In this study we compared the effect of a movement-focused practice and a breath
      focused practice on stress parameters (perceived stress and salivary cortisol)
      and sustained attention (response inhibition) in yoga naive university students.
      While participants of both programs showed a reduction in perceived stress and
      salivary cortisol, only the breath-focused group showed improvements in sustained
      attention. In addition, improvement in sustained attention was correlated with
      reduction in perceived stress but not with reduction in salivary cortisol. We
      discuss these findings in the context of a theoretical framework outlining bottom
      up neurophysiological and top-down neurocognitive mechanisms hypothesized to be
      engaged by YBP.

PMID- 30099317
TI  - Shape and non-bonding interactions in the formic acid-difluoromethane complex by
      rotational spectroscopy.
AB  - The rotational spectrum of the formic acid-difluoromethane complex was measured
      by using supersonic-jet Fourier transform microwave spectrometer. Experimental
      results and ab initio calculations support a conformation formed through a
      relative strong OH?F and a bifurcated weak CH2?O hydrogen bonds. The distances of
      the non-bonding interactions were determined to be 1.960(2) A and 2.797(3) A for
      OH?F and CH2?O, respectively. The dissociation energy of the complex is estimated
      to be about 1346 cm-1. The bonding nature of the intermolecular interactions was
      revealed by non-covalent interaction analysis and electron density difference
      analysis.

PMID- 30099319
TI  - Assessment of microplastics derived from mariculture in Xiangshan Bay, China.
AB  - Mariculture activities including enclosure, raft and cage cultures employ a
      variety of plastic gear such as fishing nets, buoyant material and net cages. The
      plastic gear poses a potential source of microplastics to the coastal
      environment, but relevant data on the impacts of mariculture are still limited.
      To this end, a semi-enclosed narrow bay (i.e., Xiangshan Bay, China) with a long
      term mariculture history was investigated to assess how mariculture activities
      affect microplastics in seawater and sediment. The results indicated that
      mariculture-derived microplastics accounted for approximately 55.7% and 36.8% of
      the microplastics in seawater and sediment, respectively. The average
      microplastic abundances of seawater and sediment were 8.9 +/- 4.7 (mean +/- SD, n
      = 18) items/m3 seawater and 1739 +/- 2153 (n = 18) items/kg sediment,
      respectively. The types of mariculture-derived microplastics included
      polyethylene (PE) foam, PE nets, PE film, polypropylene (PP) rope, polystyrene
      (PS) foam and rubber. PE foam had the highest proportion (38.6%) in the seawater
      samples. High usage rates and the porous structure of PE foam led to the high
      abundance. The average microplastic sizes of seawater and sediment are 1.54 +/-
      1.53 mm and 1.33 +/- 1.69 mm, respectively. The spatial variations in the
      abundance and size of microplastics implied that the mariculture-derived
      microplastics in Xiangshan Bay were transported along the Bay to the open sea.
      The results of this study indicate that mariculture activity can be a significant
      source of microplastics. Further research is required to investigate how the high
      microplastic abundance in mariculture zone affects marine organisms, especially
      cultured seafood.

PMID- 30099320
TI  - Potential-resolved Faraday cage-type electrochemiluminescence biosensor for
      simultaneous determination of miRNAs using functionalized g-C3N4 and metal
      organic framework nanosheets.
AB  - Here, a novel Faraday cage-type electrochemiluminescence (ECL) biosensor was
      presented for simultaneous determination of miRNA-141 and miRNA-21 based on the
      potential-resolved strategy. In this work, capture units were prepared by
      immobilizing hairpin DNA1 (HP1) and hairpin DNA2 (HP2) on Fe3O4 @Au
      nanocomposites, while g-C3N4 @AuNPs nanocomposites labelled by signal DNA1
      (sDNA1) and ruthenium-based metal organic framework (Ru-MOF) nanosheets labelled
      by signal DNA2 (sDNA2) were used as signal units. In this proposed biosensor,
      signal units g-C3N4 @AuNPs-sDNA1 and Ru-MOF-sDNA2 could exhibit two strong and
      stable ECL emissions at - 1.4 V and + 1.5 V respectively, which could be used as
      effective potential-resolved signal tags. Moreover, taking advantage of the
      proposed Faraday cage-type model, all electrochemiluminophores in the signal
      units could take part in electrode reactions, the signal units became part of the
      electrode surface and extended the outer Helmholtz plane (OHP) of the proposed
      electrode, and then the detection sensitivity was improved greatly. Accordingly,
      dual targets miRNA-141 and miRNA-21 could be detected within the linear range of
      1 fM to 10 pM, with the detection limit of 0.3 fM. Meanwhile, the proposed miRNA
      assay exhibited high selectivity and sensitivity, even for practical analysis in
      human serum. So, this potential-resolved ECL biosensor is proved to be a feasible
      tool for dual targets detection of miRNAs in clinical diagnosis.

PMID- 30099321
TI  - The defective component of viral populations.
AB  - Particles containing degenerate forms of the viral genome which interfere with
      virus replication and are non-replicative per se are known as defective
      interfering particles (DIPs). DIPs are likely to be produced upon infection by
      any virus in vitro and in nature. Until recently, roles of these non-viable
      particles as members of a multi-component viral system have been overlooked. In
      this review, we cover the most recent studies that shed light on critical roles
      of DIPs during the course of infection, including: the modulation of virus
      replication, innate immune responses, disease outcome and virus persistence, as
      well as the evolution of the viral population. Together, these reports allow us
      to conceive a more complete picture of the virion population, and highlight the
      fact that DIPs are not a negligible subset of this population but instead can
      greatly influence the fate of infection.

PMID- 30099322
TI  - Graph structured autoencoder.
AB  - In this work, we introduce the graph regularized autoencoder. We propose three
      variants. The first one is the unsupervised version. The second one is tailored
      for clustering, by incorporating subspace clustering terms into the autoencoder
      formulation. The third is a supervised label consistent autoencoder suitable for
      single label and multi-label classification problems. Each of these has been
      compared with the state-of-the-art on benchmark datasets. The problems addressed
      here are image denoising, clustering and classification. Our proposed methods
      excel of the existing techniques in all of the problems.

PMID- 30099323
TI  - Pinning impulsive synchronization for stochastic reaction-diffusion dynamical
      networks with delay.
AB  - This paper considers the problem of the asymptotic synchronization in mean square
      for stochastic reaction-diffusion complex dynamical networks with infinite delay
      driven by the Wiener processes in the infinite dimensional space under the
      pinning impulsive control. Two types of the impulsive controllers are proposed:
      the first is a single pinning impulsive controller on the first node, and the
      second is the pinning impulsive controller on a small portion of the network
      nodes. By using the variation-of-constant formula and the fixed point theorem,
      the asymptotic behavior of impulsive differential equations with infinite delay
      is first analyzed. Then, by introducing some operators in the abstract space, the
      networks are transformed into a set of stochastic coupled impulsive partial
      differential equations in Hilbert space. Under these two pinning impulsive
      control types, the asymptotic stability in mean square of stochastic coupled
      partial differential equations is examined by Lyapunov function approach and the
      comparison principle. The asymptotic synchronization in mean square of stochastic
      reaction-diffusion dynamical networks can be realized for these two pinning
      impulsive control schemes. One example is provided to present the potential
      application of the theoretic results obtained.

PMID- 30099324
TI  - [omim][BF4]-mediated toxicity in mussel hemocytes includes its interaction with
      cellular membrane proteins.
AB  - The current study is based on the increasing demand for the assessment of ionic
      liquid (IL)-mediated aquatic toxicity. Specifically, although a lot of studies
      have been performed so far, investigating IL-mediated adverse effects on numerous
      aquatic organisms, little is known about their mode of action. Given that the use
      of in vitro models is considered as a reliable tool for determining the mediated
      biological effects, the modulation of specific biochemical pathways and the onset
      of various forms of damage with great precision and reproducibility, mixed
      primary cultures of mussel Mytilus galloprovincialis hemocytes were used for
      investigating whether 1-octyl-3-methylimidazolium tetrafluoroborate ([omim][BF4])
      mediated toxicity is related to its interaction with cellular membrane proteins.
      Specifically, [omim][BF4]-mediated cytotoxic, oxidative and genotoxic effects
      were investigated in mussel hemocytes before and after pre-treatment of cells
      with non-toxic concentration of guanidine hydrochloride (1 mM GndHCl). The
      results showed that [omim][BF4] at concentrations ranging from 0.7 to 1.75 MUM
      can induce cytotoxic (almost <50% reduction of cell viability), oxidative
      (increased levels of O2*- production and lipid peroxidation by-products) and
      genotoxic (increased levels of DNA damage) effects, while cells pre-treated with
      1 mM GndHCl showed a significant attenuation of IL's toxic potency in all cases.
      According to the latter, the current study showed that [omim][BF4]-mediated
      toxicity could be related not only to its well-known interaction with membrane
      lipid bilayers, but also to its interference with membrane proteins. Using
      GndHCl, a chaotropic agent that disrupts the hydrogen bonding network and the
      stability of membrane proteins via its interference with the intramolecular
      interactions mediated by non-covalent forces on cellular membranes, it was
      firstly shown that altering the membrane integrity as well as the native state of
      cellular membrane proteins, by weakening the hydrophobic effect, could attenuate
      the possible interaction of [omim][BF4] with cellular membranes and the
      concomitant induction of protein-based intracellular processes, commonly linked
      with the induction of severe cellular damage.

PMID- 30099325
TI  - Sex-specific immunomodulatory action of the environmentalestrogen 17alpha
      ethynylestradiol alongside with reproductive impairment in fish.
AB  - Estrogenic endocrine disrupting chemicals (EEDCs) are present ubiquitously in
      sediments and aquatic ecosystems worldwide. The detrimental impact of EEDCs on
      the reproduction of wildlife is widely recognized. Increasing evidence shows the
      immunosuppressive effects of EEDCs in vertebrates. Yet, no studies have
      considered concomitantly EEDC-induced impacts on reproductive impairment and
      immune suppression in vivo, which are deemed essential for risk assessment and
      environmental monitoring. In this study, EE2 was used as a representative EEDC,
      for parallel evaluation of EEDC-induced immune suppression (immune marker gene
      expression, leukocyte numbers, host resistance assay, and immune competence
      index) and reproductive impairment (estrogen responsive gene expression,
      fecundity, fertilization success, hatching success, and reproductive competence
      index) in an established fish model (marine medaka Oryzias melastigma),
      considering sex-specific induction and adaptation and recovery responses under
      different EE2 exposure scenarios. The findings in marine medaka reveal distinct
      sex differences in the EE2-mediated biological responses. For female fish, low
      concentration of exogenous EE2 (33 ng/L) could induce hormesis (immune
      enhancement), enable adaptation (restored reproduction) and even boost fish
      resistance to bacterial challenge after abatement of EE2. However, a prolonged
      exposure to high levels of EE2 (113 ng/L) not only impaired F0 immune function,
      but also perturbed females recovering from reproductive impairment, resulting in
      a persistent impact on the F1 generation output. Thus, for female fish, the
      exposure concentration of EE2 is more critical than the dose of EE2 in
      determining the impacts of EE2 on immune function and reproduction. Conversely,
      male fish are far more sensitive than females to the presence of low levels of
      exogenous EE2 in water and the EE2-mediated biological impacts are clearly dose
      dependent. It is also evident in male fish that direct contact of EE2 is
      essential to sustain impairments of immune competence and reproductive output as
      well as deregulation of immune function genes in vivo. The immunomodulatory
      pathways altered by EE2 were deciphered for male and female fish, separately.
      Downregulation of hepatic tlr3 and c3 (in female) and tlr3, tlr5 and c3 (in male)
      may be indicative of impaired fish immune competence. Taken together, impaired
      immune competence in the EE2-exposed fish poses an immediate thread on the
      survival of F0 population. Impaired reproduction in the EE2-exposed fish can
      directly affect F1 output. Parallel evaluation of immune competence and
      reproduction are important considerations when assessing the risk of sublethal
      levels of EE2/EEDCs in aquatic environments.

PMID- 30099326
TI  - Impact of subtypes and comorbidities on breast cancer relapse and survival in
      population-based studies.
AB  - OBJECTIVE: To study the impact of subtypes and comorbidities on breast cancer
      (BC) relapse and survival in the heterogeneous patients of the real world.
      METHODS: We identified patients diagnosed with BC between January 2003 and
      December 2005 from six population-based Swiss cancer registries.
      Clinicopathologic data was completed with information on locoregional and distant
      relapse and date and cause of death for over 10-years. We approximated BC
      subtypes using grade and the immunohistochemical panel for oestrogen,
      progesterone and human epidermal growth factor 2 (HER2) receptor status. We
      studied factors affecting relapse and survival. RESULTS: Luminal A-like subtype
      represented 46% of all newly diagnosed BC (N = 1831), followed by luminal B-like
      (N = 1504, 38%), triple negative (N = 436, 11%) and HER2 enriched (N = 204, 5%).
      We observed regional disparities in subtype prevalence that contribute to explain
      regional differences in survival formerly described. Disease relapse and BC
      specific mortality differed by subtype and were lower for luminal A like tumours
      than for other subtypes for any stage at diagnosis. After a median follow-up of
      10.9 years, 1311 (33%) had died, half of them 647 (16%) due to another disease,
      showing the importance of comorbidities. Omission of systemic therapies in
      selected patients was not associated with poorer BC specific survival, BC subtype
      and life expectancy playing a role. CONCLUSIONS: Information on tumour subtype is
      necessary for an adequate interpretation of population-based BC studies. Measures
      of comorbidity or frailty help in the evaluation of quality of care in the highly
      heterogeneous patients of the real world.

PMID- 30099327
TI  - A cost-utility analysis comparing large volume displacement oncoplastic surgery
      to mastectomy with single stage implant reconstruction in the treatment of breast
      cancer.
AB  - BACKGROUND: For larger cancers in moderate to large breast sized women, breast
      surgical cancer treatment may include large volume displacement oncoplastic
      surgery (LVOS) or mastectomy with single stage implant reconstruction (SSIR).
      Often in the case of LVOS, reduction mammaplasty designs are used in the
      oncoplastic reconstructions with a contralateral symmetry operation. The goal of
      this study was to investigate the cost-utility between LVOS versus SSIR to
      determine which approach is cost-effective in the treatment of breast cancer.
      METHODS: A review of the literature was performed to determine baseline values
      and ranges. An average national Medicare payment rates using DRG and CPT codes
      were used for cost assessment. After constructing a decision tree, an incremental
      cost-utility ratio (ICUR) was calculated comparing the difference for both
      surgical options in costs by the difference in clinical-effectiveness. To
      validate our results, we performed one-way sensitivity analyses in addition to a
      Monte-Carlo analysis. RESULTS: An ICUR of $546.81/QALY favoring LVOS was
      calculated based off of its clinical-effectiveness gain of 7.67 QALY at an
      additional cost of $4194. One-way sensitivity analyses underscored the degree by
      which LVOS was cost-effective. For example, LVOS became cost-ineffective when a
      successful LVOS cost more than $50,000. Similarly, probabilistic sensitivity
      analysis using Monte-Carlo simulation showed that even with varying multiple
      variables at once, results tended to favor our conclusion supporting the cost
      effectiveness of LVOS. CONCLUSIONS: For the appropriate patients with moderate to
      large sized breasts with breast cancer, large volume displacement oncoplastic
      surgery is cost-effective compared to mastectomy with single staged implant
      reconstruction.

PMID- 30099328
TI  - Recommendation to use exact P-values in biomarker discovery research in place of
      approximate P-values.
AB  - BACKGROUND: Biomarker candidates are often ranked using P-values. Standard P
      value calculations use normal or logit-normal approximations, which may not be
      correct for small P-values and small sample sizes common in discovery research.
      METHODS: We compared exact P-values, correct by definition, with logit-normal
      approximations in a simulated study of 40 cases and 160 controls. The key measure
      of biomarker performance was sensitivity at 90% specificity. Data for 3000
      uninformative false markers and 30 informative true markers were generated
      randomly. We also analyzed real data for 2371 plasma protein markers measured in
      121 breast cancer cases and 121 controls. RESULTS: In our simulation, using the
      same discovery criterion, exact P-values led to discovery of 24 true and 82 false
      biomarkers, while logit-normal approximate P-values yielded 20 true and 106 false
      biomarkers. The estimated true discovery rate was substantially off for
      approximate P-values: logit-normal estimated 42 but found 20. The exact method
      estimated 22, very close to 24, which was the actual number of true discoveries.
      Although these results are based on one specific simulation, qualitatively
      similar results were obtained from 10 random repetitions. With real data, ranking
      candidate biomarkers by exact P-values, versus approximate P-values, resulted in
      a very different ordering of these markers. CONCLUSIONS: Exact P-values, which
      correspond to permutation tests with non-parametric rank statistics such as
      empirical ROC statistics, are preferred over approximate P-values. Approximate P
      values can lead to inappropriate biomarker selection rules and incorrect
      conclusions. IMPACT: Exact P-values in place of approximate P-values in discovery
      research may improve the yield of biomarkers that validate clinically.

PMID- 30099329
TI  - Effect of maternal weight during pregnancy on offspring muscle strength response
      to resistance training in late adulthood.
AB  - PURPOSE: Maternal obesity can unfavorably influence offspring body composition,
      muscle strength, and possibly muscle's adaptability to training, but the human
      studies are scarce. Therefore, we aimed to investigate the effect of maternal
      obesity on offspring muscle strength responses to resistance training
      intervention in elderly frail women. MATERIALS/METHODS: Recruited participants
      were elderly frail women offspring of lean/normal weight mothers (n = 19, mean
      body mass index (BMI): 22.8 kg/m2, range: 19.9-24.5) or overweight/obese mothers
      (n = 16, mean BMI: 29.7 kg/m2, range: 28.2-34.2). Information on maternal BMI
      immediately prior to delivery was collected from the birth registers. All women
      participated in a 4-month supervised progressive resistance training intervention
      three times a week for 60 min. Predicted 1-RM of abdominal crunch, hip abduction,
      leg curl, leg press, seated row, and total strength were measured at baseline and
      after each month of training. RESULTS: According to rANOVA, strength increased
      significantly in both groups (p for time <0.001), but no significant between the
      group difference were detected (p for time x group interaction > 0.072). On
      average, muscle strength of the women offspring of overweight/obese mothers
      tended to be lower than in women offspring of lean/normal weight mothers, but the
      only significant difference was found in leg curl (p = 0.006). No significant
      differences between the groups were found in relative strength changes from
      baseline to 4-months. CONCLUSIONS: Muscle strength response to supervised
      resistance training is not modulated by maternal adiposity in late pregnancy in
      elderly frail female offspring.

PMID- 30099330
TI  - Secondary EMR data for quality improvement and research: A comparison of manual
      and electronic data collection from an integrated critical care electronic
      medical record system.
AB  - PURPOSE: This study measured the quality of data extracted from a clinical
      information system widely used for critical care quality improvement and
      research. MATERIALS AND METHODS: We abstracted data from 30 fields in a random
      sample of 207 patients admitted to nine adult, medical-surgical intensive care
      units. We assessed concordance between data collected: (1) manually from the
      bedside system (eCritical MetaVision) by trained auditors, and (2) electronically
      from the system data warehouse (eCritical TRACER). Agreement was assessed using
      Cohen's Kappa for categorical variables and intraclass correlation coefficient
      (ICC) for continuous variables. RESULTS: Concordance between data sets was
      excellent. There was perfect agreement for 11/30 variables (35%). The median
      Kappa score for the 16 categorical variables was 0.99 (IQR 0.92-1.00). APACHE II
      had an ICC of 0.936 (0.898-0.960). The lowest concordance was observed for SOFA
      renal and respiratory components (ICC 0.804 and 0.846, respectively). Score
      translation errors by the manual auditor were the most common source of data
      discrepancies. CONCLUSIONS: Manual validation processes of electronic data are
      complex in comparison to validation of traditional clinical documentation. This
      study represents a straightforward approach to validate the use of data
      repositories to support reliable and efficient use of high quality secondary use
      data.

PMID- 30099331
TI  - Defining and defending drug-free bodybuilding: A current perspective from
      organisations and their key figures.
AB  - The use of performance- and image-enhancing drugs in the past seventy years or so
      has sparked a number of responses, including heated public debates, the creation
      of dedicated organisations and drug policies, as well as the emergence of
      communities of practice and belief in support of or in opposition to the
      phenomenon. Drug-free, known in the field as 'natural', bodybuilding has been
      developing since the 1970 s as a response to a dominant bodybuilding culture
      where the use of performance- and image-enhancing drugs has become normalised.
      Recent years have seen a multiplication of national and international governing
      bodies, competitions, and participants in drug-free bodybuilding in different
      parts of the globe. As the field grows, the questions of what constitutes natural
      bodybuilding and who can authentically represent it become central. Adopting a
      multi-method, qualitative approach, this article explores the ways organisations
      and their key figures define and defend their versions of drug-free bodybuilding.
      The discussion focus is on the policies, meanings and identities embedded in
      these different versions, and how their production and negotiation makes sense in
      light of antagonisms between players in the field of natural bodybuilding as well
      as their relation to drug-enhanced bodybuilding and the wider world of sport. In
      examining this previously uncharted body culture, the article explores how the
      use of performance- and image-enhancing drugs provokes responses and processes of
      contestation and differentiation. In the process, what becomes apparent is the
      designation and negotiation of drug-free, natural bodies as an ongoing, dynamic,
      social process.

PMID- 30099332
TI  - Multifrequency Kelvin probe force microscopy on self assembled molecular layers
      and quantitative assessment of images' quality.
AB  - The application of single-pass multifrequency Kelvin probe force microscopy
      (KPFM) for topography and contact potential difference (CPD) measurements of
      organic self-assembled monolayers (SAM) is demonstrated. Four modes of mechanical
      and electrical cantilever excitation were tested in order to obtain the best
      possible resolution in the CPD measurements. The algorithm using maximum capacity
      of information channel for quantitative image quality assessment was proposed to
      compare and assess the quality of the recorded images and imaging modes. The
      improvement of the quality of CPD imaging in multiresonance operation was
      confirmed.

PMID- 30099333
TI  - Generation of patient-specific induced pluripotent stem cell lines from one
      patient with Jervell and Lange-Nielsen syndrome, one with type 1 long QT syndrome
      and two healthy relatives.
AB  - Four human iPSC cell lines (one Jervell and Lange-Nielsen Syndrome, one Long QT
      Syndrome-type 1 and two healthy controls) were generated from peripheral blood
      obtained from donors belonging to the same family. CytoTuneTM-iPS 2.0 Sendai
      Reprogramming Kit (containing OCT3/4, KLF4, SOX2 and cMYC as reprogramming
      factors) was used to generate all cell lines. The four iPSCs have normal
      karyotype, express pluripotency markers as determined by RT-PCR and flow
      cytometry and differentiated spontaneously in vitro into cells of the three germ
      layers, confirming their pluripotent capacity.

PMID- 30099334
TI  - Generation of a human induced pluripotent stem cell line (LL008 1.4) from a
      familial Alzheimer's disease patient carrying a double KM670/671NL (Swedish)
      mutation in APP gene.
AB  - A double mutation (KM670/671NL) in amyloid precursor protein gene (APP) is
      causative for familial Alzheimer's disease and has been shown to increase the
      total Abeta burden. Here we report the generation and characterization of an iPSC
      line from a fAD patient carrying APP KM670/671NL. The generated iPSCs retained
      the mutation, expressed pluripotency markers, showed a normal karyotype and
      differentiated into all three germ layers. This iPSC line can be used, for
      example, in disease modeling and mechanistic studies. Resource table.

PMID- 30099335
TI  - Improving single-cell cloning workflow for gene editing in human pluripotent stem
      cells.
AB  - The availability of human pluripotent stem cells (hPSCs) and progress in genome
      engineering technology have altered the way we approach scientific research and
      drug development screens. Unfortunately, the procedures for genome editing of
      hPSCs often subject cells to harsh conditions that compromise viability: a major
      problem that is compounded by the innate challenge of single-cell culture. Here
      we describe a generally applicable workflow that supports single-cell cloning and
      expansion of hPSCs after genome editing and single-cell sorting. Stem-Flex and
      RevitaCell supplement, in combination with Geltrex or Vitronectin (VN), promote
      reliable single-cell growth in a feeder-free and defined environment.
      Characterization of final genome-edited clones reveals that pluripotency and
      normal karyotype are retained following this single-cell culture protocol. This
      time-efficient and simplified culture method paves the way for high-throughput
      hPSC culture and will be valuable for both basic research and clinical
      applications.

PMID- 30099336
TI  - Generation of nine induced pluripotent stem cell lines as an ethnic diversity
      panel.
AB  - Human induced pluripotent stem cells (iPSCs) provide a potentially unlimited
      source of differentiated cells from individuals with specific genetic
      backgrounds. Using self-replicative RNA reprogramming technology, we generated
      nine iPSC lines from endothelial progenitor cells (EPCs) derived from blood
      samples of three different ethnicities: Black or African American, Latino or
      Hispanic, and Non-Hispanic White. The resulting iPSC lines showed normal
      karyotype in large part, expressed pluripotency marker genes, and spontaneously
      differentiated in vitro into the three germ layers. These iPSC lines offer the
      potential to generate tissues with ethnic diversity, and thus afford a valuable
      tool for ethnic-related toxicological applications.

PMID- 30099338
TI  - Sitagliptin attenuates myocardial apoptosis via activating LKB-1/AMPK/Akt pathway
      and suppressing the activity of GSK-3beta and p38alpha/MAPK in a rat model of
      diabetic cardiomyopathy.
AB  - The present study aimed to investigate the protective effect of sitagliptin, a
      dipeptidyl peptidase-4 inhibitor, on diabetic cardiomyopathy (DCM)-associated
      apoptosis and if this effect is mediated via modulating the activity of the
      survival kinases; AMP-activated protein kinase (AMPK) and Akt & the apoptotic
      kinases; glycogen synthase kinase-3 beta (GSK-3beta) and p38 mitogen-activated
      protein kinase (p38MAPK). Diabetes was induced by a single intraperitoneal
      injection of streptozotocin (55 mg/kg). Diabetic rats were treated with
      sitagliptin (10 mg/kg/day, p.o.) and metformin (200 mg/kg/day, p.o. as positive
      control) for six weeks. Chronic hyperglycemia resulted in elevation of serum
      cardiac biomarkers reflecting cardiac damage which was supported by H&E stain.
      The mRNA levels of collagen types I and III were augmented reflecting cardiac
      fibrosis and hypertrophy which was supported by Masson trichome stain and
      enhanced phosphorylation of p38MAPK. Cardiac protein levels of cleaved casapse-3,
      BAX were elevated, whereas, the levels of Bcl-2 and p-BAD were reduced indicating
      cardiac apoptosis which could be attributed to the diabetes-induced reduced
      phosphorylation of Akt and AMPK with concomitant augmented activation of GSK
      3beta and p38MAPK. Protein levels of liver kinase B-1, the upstream kinase of
      AMPK were also supressed. Sitagliptin administration alleviated the decreased
      phosphorylation of AMPK and Akt, inactivated the GSK-3beta and p38 AMPK,
      therefore, attenuating the apoptosis and hypertrophy induced by hyperglycemia in
      the diabetic heart. In conclusion, sitagliptin exhibits valuable therapeutic
      potential in the management of DCM by attenuating apoptosis. The underlying
      mechanism may involve the modulating activity of AMPK, Akt, GSK-3beta and
      p38MAPK.

PMID- 30099339
TI  - MiR-148b-3p inhibits renal carcinoma cell growth and pro-angiogenic phenotype of
      endothelial cell potentially by modulating FGF2.
AB  - MicroRNAs (miRNAs) have been implicated in a large number of biological processes
      such as tumor angiogenesis. MiR-148b-3p has been identified as a tumor suppressor
      in multiple cancer types and the function of miR-148b-3p in renal carcinoma
      remains unidentified. In this study, we found that the expression of miR-148b-3p
      was decreased in renal carcinoma based on GEO analysis and the gain-of-function
      experiments revealed that miR-148b-3p promoted renal carcinoma cell apoptosis and
      suppressed cell proliferation, migration in vitro and tumor growth in vivo.
      Functionally, the tube formation, invasion and migration capabilities of human
      umbilical vein endothelial cells (HUVECs) were suppressed by conditioned media
      derived from renal carcinoma 786-O cells that were transfected with miR-148b-3p
      mimics. Meanwhile, these conditioned media inhibited the proliferation and
      promoted apoptosis of HUVECs. The key angiogenesis inducer hypoxia inducible
      factor-1alpha (HIF-1alpha) and the pro-angiogenic mediators were decreased in 786
      O cells that were transfected with miR-148b-3p mimics. Mechanistically, miR-148b
      3p could target fibroblast growth factor-2 (FGF2) and further impaired the
      activation of fibroblast growth factor receptor 2 (FGFR2). Taken together, our
      findings demonstrate that miR-148b-3p attenuates renal carcinoma cell growth, the
      invasion and tube formation of endothelial cell potentially via regulating FGF2
      FGFR2 signaling pathway.

PMID- 30099340
TI  - Methanolic extract of Morinda citrifolia Linn. unripe fruit attenuates
      methamphetamine-induced conditioned place preferences in mice.
AB  - The first objective of the present study was to determine the appropriate dose of
      methamphetamine (Meth) to induce a successful conditioned place preference (CPP)
      in mice. The next objective was to examine the effect of a methanolic extract of
      M. citrifolia unripe fruit (MMC) against Meth-induced CPP in mice. In answering
      to the first objective, following the preconditioning test, an intraperitoneal
      injection of a fixed dose of Meth (0.5 or 1 or 2 mg/kg, i.p.) or saline (10
      ml/kg, i.p.) was given on alternate days during the 10 days conditioning period
      followed by a postconditioning test conducted in Meth-free state. The first
      experiment revealed that 0.5 mg/kg of Meth could be an appropriate fixed low dose
      to induce CPP in mice. Meanwhile, in other experiments, the effect of MMC and
      bupropion (BUPR) against the expression, extinction, and reinstatement of Meth
      (0.5 mg/kg)-induced CPP in mice, respectively, was investigated. In a separate
      set of studies on each phase, an oral administration of MMC (1, 3 and 5 g/kg,
      p.o.) or BUPR (20 mg/kg, p.o.) was given 60 min prior to CPP postconditioning
      testing or extinction testing or reinstatement testing in mice. Extinction trials
      were conducted in Meth-free state to weaken CPP over the next 5 days.
      Reinstatement test was conducted by a single low dose priming injection of Meth
      (0.1 mg/kg, i.p.). The present study, however, failed to establish a successful
      extinction and reinstatement of Meth-CPP in mice. Further studies using other
      doses of Meth are warranted for a successful establishment of all phases of Meth
      CPP in mice. This study also demonstrates that MMC (3 and 5 g/kg, p.o.) and BUPR
      (20 mg/kg, p.o.) could attenuate the expression of Meth-induced CPP in mice.

PMID- 30099337
TI  - Association of N-terminal pro B-type natriuretic peptide (NT-proBNP) change with
      the risk of atrial fibrillation in the ARIC cohort.
AB  - BACKGROUND: Circulating N-terminal pro B-type natriuretic peptide (NT-proBNP)
      predicts incidence of atrial fibrillation (AF), but the association of
      longitudinal changes in NT-proBNP concentrations with incident AF has not been
      explored. METHODS: We studied 9705 individuals without prevalent AF in 1996-1998
      and with available NT-proBNP measurements obtained in samples collected during
      two visits in 1990-1992 (visit 2) and 1996-1998 (visit 4) in the Atherosclerosis
      Risk in Communities (ARIC) Study. Participants were followed through the end of
      2013. AF was ascertained from electrocardiograms, hospital discharge codes, and
      death certificates. Multivariable Cox regression was used to evaluate the
      association of absolute change in log-transformed NT-proBNP [ln(NT-proBNP)] with
      incident AF. We also assessed the impact of adding ln(NT-proBNP) change as a
      predictor of AF by difference in the C-statistic and net reclassification
      improvement (NRI). RESULTS: Over a median follow up of 16 years, there were 1503
      incident cases of AF. The means (SD) ln(NT-proBNP) at visit 2 and visit 4 were
      3.83 (1.01) and 4.35 (0.94), respectively. There was a 0.52 (0.79) increase in
      ln(NT-proBNP) over the 6-year period. Greater increases in ln(NT-proBNP) were
      associated with higher risk of AF [hazard ratio, 2.82 (95% confidence interval
      2.34, 3.39), comparing top to bottom quintiles, and 1.74 (1.61, 1.87) per 1-unit
      increase in ln(NT-proBNP)]. Adding ln(NT-proBNP) change to a model with multiple
      predictors including baseline NT-proBNP had relatively limited impact in the C
      statistic (increase from 0.748, 95%CI 0.736-0.761, to 0.762, 95%CI 0.750, 0.774).
      Adding ln(NT-proBNP) change to initial predictive models resulted in a
      categorical NRI of 0.062 (95% CI 0.033, 0.092) and a continuous NRI of 0.092
      (95%CI, 0.017, 0.182). CONCLUSION: Positive NT-proBNP change is associated with
      an increased incidence rate of AF. Adding NT-proBNP change into the prediction
      model modestly improved incident AF prediction. Future studies should assess the
      value of monitoring NT-proBNP concentration among individuals at high risk of
      developing AF.

PMID- 30099341
TI  - Leucodin attenuates inflammatory response in macrophages and lipid accumulation
      in steatotic hepatocytes via P2x7 receptor pathway: A potential role in alcoholic
      liver disease.
AB  - The current study was aimed to reveal that leucodin, a sesquiterpene lactone from
      Artemisia capillaris could inhibit the inflammatory response in macrophages and
      the lipid accumulation in hepatocytes via P2x7R-NLRP3 inflammasome activation.
      Several types of macrophages including mouse peritoneal macrophages, mouse bone
      marrow-derived macrophages and human macrophages THP-1 cells were pretreated with
      different concentrations of leucodin for 1 h and then stimulated with LPS and
      ATP. LPS plus ATP initiated IL-1beta cleavage and release in mouse peritoneal
      macrophages and peaked at 4 h. Leucodin did not show significant toxicity within
      200 MUM and effectively inhibited pro-IL-1beta cleavage and release of mature-IL
      1beta in macrophages. Also, P2x7R antagonist and caspase-1 inhibitor also
      decreased IL-1beta release and cleavage. Additionally, leucodin suppressed P2x7R,
      TLR4 and NLRP3 expression in LPS/ATP-stimulated macrophages. HepG2 cells were
      pretreated with different concentrations of leucodin for 1 h and then exposed to
      ethanol for 24 h. Leucodin suppressed lipid accumulation and enhanced
      phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase
      (ACC) in HepG2 cells exposed to ethanol. In addition, leucodin inhibited the
      expression of sterol regulatory element binding protein-1 (SREBP1) and ACC in
      ethanol-treated HepG2 cells. Leucodin possessed the capacity for inhibiting
      inflammatory response in macrophages and suppressing lipid accumulation in
      hepatocytes, suggesting a promising therapeutic potential targeting inflammation
      and lipid metabolism in alcoholic liver disease.

PMID- 30099342
TI  - Long noncoding RNA kcna3 inhibits the progression of colorectal carcinoma through
      down-regulating YAP1 expression.
AB  - Long non-coding RNAs (lncRNAs) regulate diverse cellular processes, and their
      anomalous expression exert an essential role in the progression of many kinds of
      cancers, including colorectal carcinoma (CRC). The objective of this study was to
      investigate the role of lncRNA kcna3 and its underlying mechanism in CRC
      progression. The expression of lncRNA kcna3 in human CRC tissues and the adjacent
      non-tumor tissues was evaluated by RT-PCR. The correlations between lncRNA kcna3
      expression levels and the overall survival (OS), as well as the
      clinicopathological features of CRC patients were analyzed. Gain-of-function and
      loss-of-function experiments were used to evaluate the effects of lncRNA kcna3 on
      the proliferation, apoptosis, migration, invasion and tumorigenesis of colon
      cancer SW620 cells. We found that lncRNA kcna3 was lowly expressed in CRC
      tissues, and its low expression was closely associated with patients' higher TNM
      grade and the higher occurrence rate of lymphatic metastasis and distant
      metastasis, as well as shorter OS. Enhanced expression of lncRNA kcna3 inhibited
      SW620 cells' proliferation, migration and invasion, and induced cell apoptosis in
      vitro, and repressed CRC tumor growth in vivo. Whereas knockdown of lncRNA kcna3
      showed the opposite results. Mechanistically, up-regulation of lncRNA kcna3
      decreased YAP1 protein expression and accelerated its degradation. The effects of
      lncRNA kcna3 overexpression on cell growth and tumorigenesis inhibition and
      apoptosis promotion were weakened when the expression of YAP1 was up-regulated.
      In conclusion, this study revealed that lncRNA kcna3 exerts a tumor-inhibit role
      in CRC progression through down-regulating YAP1 expression, indicating that
      lncRNA kcna3/YAP1 might be served as a new prognostic biomarker and therapeutic
      target for CRC.

PMID- 30099343
TI  - Cathepsin B contributes to radioresistance by enhancing homologous recombination
      in glioblastoma.
AB  - Resistance to adjuvant radiotherapy is a major cause of treatment failure in
      patients with glioblastoma (GBM). Recently, the role of lysosome, especially
      lysosomal proteases, in radioresistance is being paid more and more attention to.
      Here, we investigated the radioresistant role of Cathepsin B (CTSB), one
      important member of cysteine proteases, in GBM cell lines. A protease array kit
      was used to test GBM cells before and after irradiation. Nude mice were implanted
      with GBM cells to generate orthotopic xenografts for in vivo studies. Response of
      U87 and U251 cells to treatment was examined using cell viability, flow
      cytometry. Cells were transfected with siRNA knockdown and gene expression
      constructs and molecules potentially mediating response were examined through
      western blot analysis, PCR and EdU assay. The results from protease array kit
      showed that CTSB was up-regulated the most among all proteases after irradiation.
      And this was verified by western blot analysis and immunohistochemistry of tumor
      samples both from in vivo study and clinical patients. Compared to negative
      control group, knocking down CTSB led to radiosensitivity. And this
      radiosensitive effect was achieved by decreasing homologous recombination (HR)
      efficiency. Further study showed that knocking down CTSB caused cell cycle
      arrested in G0/G1 phases, in which HR efficiency was impaired. Knocking down CTSB
      contributed to radiosensitivity in GBM cells by causing cell cycle arrest and
      down-regulating HR efficiency.

PMID- 30099344
TI  - Rosmarinic acid influences collagen, MMPs, TIMPs, glycosylation and MUC1 in CRL
      1739 gastric cancer cell line.
AB  - Rosmarinic acid (RA) is a natural phenylpropanoid with numerous pharmacological
      activities. Because of limited studies of the effects of RA action in gastric
      cancer cells we examined how 100 and 200 MUM acid influences MMPs, TIMPs,
      collagen, MUC1 and specific sugar antigens in gastric adenocarcinoma CRL-1739
      cells. We revealed inhibitory effect of RA on MMP-9 activity what was correlated
      with increased collagen type I expression, main ECM substrate degraded by MMPs.
      Tissue inhibitor of MMPs, TIMP-1 but not TIMP-2 was significantly decreased on
      the protein level and increased on mRNA level by RA action what can suggest TIMP
      1 independent inhibitory action of an acid on MMP-9 activity. Glycosylation of
      gastric cancer proteins was also effected by RA. ELISA tests revealed inhibitory
      effect of an acid on Tn antigen in cell lysates and culture supernatant and on T
      antigen in cell lysates. RA inhibited also sialylated Tn antigen in protein of
      culture supernatant and sialyl T in cell lysates. Extracellular domain of MUC1
      mucin, main carrier of Tn and T antigens was significantly inhibited by higher
      dose of RA. The data suggest potential usefulness of RA as a complementary agent
      supporting chemotherapy in cancer treatment.

PMID- 30099345
TI  - Colorectal cancer and medicinal plants: Principle findings from recent studies.
AB  - Colorectal cancer is one of the most frequent malignancies in the world. Although
      recent advances in chemotherapy have improved management and survival of
      colorectal cancer patients, side effects and resistance to chemotherapy have
      shown the limitations of current chemotherapy and led to the search for
      alternative treatments. In this context, medicinal plants provide a large number
      of molecules with proven cytotoxic and apoptogenic activities against several
      types of cancers including colorectal cancer. These molecules belong to various
      phytochemical families and trigger different signaling pathways. Here, we review
      the recent findings regarding the anti-colorectal cancer activities of several
      plants, both in vitro and in vivo, and the phytochemical molecules possibly
      responsible for these activities. Besides, their effects on several cancer
      signaling pathways are discussed. This review highlights the importance of
      medicinal plants as promising sources of lead anti-colorectal molecules.

PMID- 30099346
TI  - Recovery of latent fingermarks from brass cartridge cases: Evaluation of
      developers, analysis of surfaces and internal ballistic effects.
AB  - A study was undertaken wherein different fingermark developers were evaluated for
      the recovery of fingermarks from brass cartridge cases, besides the evaluation of
      factors such as firing effects and surface characterization of the cases. The
      latent fingermarks on alpha-brass plates, fired and unfired cartridge cases were
      deposited and aged for 1-14days before development with different developers. In
      order to mimic the fired cartridge case conditions, the brass plates were heated
      and examined at room temperature (RT), at 63 and at 200 degrees C. The sequential
      treatment with cyanoacrylate, gun blue and fluorescent dye has been found to be
      the best among other developers for the recovery of latent fingermarks on brass
      surfaces including fired and unfired cartridge cases. Cartridge cases and other
      brass surfaces were also analyzed by surface characterization methods, including
      X-ray diffraction, scanning electronic microscopy, energy dispersive X-ray
      spectroscopy and metallographic examination. The tested surfaces correspond to
      alpha-phase brass Cu0.7Zn0.3 composition and have shown different surface
      morphologies (such as grain structure) and different levels of oxidation, even
      for cartridge cases obtained from the same batch. Due to this, the effectiveness
      of a given reagent for a specific brass surface is uncertain. Therefore, the
      application of the entire tested sequence of developers is strongly recommended.
      Further, the effects of firing on fingermarks on cartridge cases were examined,
      and the results indicated that the blowback of hot gases through the looseness
      between cartridge case and chamber wall of the firearm is the main cause
      responsible for deterioration of fingermarks during firing. Despite the
      recognized damage caused to fingermarks by the firing effects, good quality
      fingermarks were recovered from fired cartridge cases in which full fingermarks
      were intentionally deposited prior to firing. This indicates that the handling of
      the cartridges before and during the loading of the gun may have a strong
      influence on the quantity and quality of fingermarks, and that the firing itself
      is not the main responsible factor for the absence or low quality of fingermarks,
      as frequently reported in fired cartridge cases studies.

PMID- 30099347
TI  - Erasure of striatal chondroitin sulfate proteoglycan-associated extracellular
      matrix rescues aging-dependent decline of motor learning.
AB  - Cognitive decline is a feature of aging. Accumulating evidence suggests that the
      brain extracellular matrix (ECM) is involved in the process of aging-dependent
      cognitive impairment and neurodegeneration by regulating synaptic
      neurotransmission and affecting neuroplasticity. Age-related changes in brain
      structure and cognition are not uniform across the whole brain. Being one of the
      most vulnerable brain regions to aging-dependent alterations, striatum is
      integral to several central nervous system functions, such as motor, cognition,
      and affective control. However, the striatal ECM is largely understudied. We
      first describe 2 major types of chondroitin sulfate proteoglycan (CSPG)
      associated ECM in striatum: perineuronal nets and diffusive ECM. Both types of
      ECM accumulate in an aging-dependent manner. The accumulation of CSPG-associated
      ECM correlates with aging-dependent decline in striatum-related cognitive
      functions, including motor learning and working memory. Enzymatic depletion of
      CSPG-associated ECM in aged mice via chondroitinase ABC significantly improves
      motor learning, suggesting that changes in neural ECM CSPGs regulate striatal
      plasticity. Our study provides a greater understanding of the role of neural ECM
      underlying striatal plasticity, which is an important precursor to design
      appropriate therapeutic strategies for normal and pathologic aging.

PMID- 30099348
TI  - The spectrum of preclinical Alzheimer's disease pathology and its modulation by
      ApoE genotype.
AB  - Sporadic Alzheimer's disease (AD) usually presents clinically after 65 years of
      age, but its pathological changes begin decades earlier. We examined for AD
      pathology in the postmortem brains of 431 of subjects aged 30-65 years not
      clinically characterized. Among 40-49 year olds, 15% showed diffuse amyloid beta
      (Abeta) plaques, with a prevalence of 80% in ApoE4/E4, 42% in E4/E3, and <1% in
      E3/E3 subjects. Abeta deposits appeared after age 49 years in subjects with E3/E3
      genotypes. Neuritic plaques first appeared after age 50 years and increased
      steadily with age in all genotypes. Insoluble Abeta42 levels were highest in
      parietal, temporal, and frontal lobes, but barely detectable in precuneus. Tau
      lesions were present in the hippocampus and entorhinal cortex in 7% of subjects
      aged <40 years and increased steadily with age reaching near 70% in the 60- to 65
      year age group. In the locus coeruleus, tau lesions were present in 72% of
      subjects aged 31-40 years and 94% in the 41- to 50-year age group. Both Abeta and
      tau lesions are present in the brains of young individuals decades before the age
      of clinical onset of AD. Abeta lesions closely correlate with the ApoE4 allele
      and appear as the earliest event in the development of senile plaques.

PMID- 30099349
TI  - Lack of a substantive effect of insurance and the national US payment system on
      the relative distribution of surgical cases among hospitals in the State of Iowa:
      A retrospective, observational, cohort study.
AB  - STUDY OBJECTIVE: Our aim was to quantify the extent to which the distribution of
      patients among payers and changes to the payers' policies has influenced the
      market of surgery among hospitals in a relatively rural state. DESIGN:
      Retrospective cohort study. SETTING: Iowa Hospital Association data analyzed were
      from 2007 through 2016 for the N = 121 hospitals with at least one case performed
      that included a major therapeutic procedure. MEASUREMENTS: We used five
      categories of payer (e.g., Medicare), five categories of patient age (e.g., 18 to
      64 years), and three categories of patient residence location (e.g., neither from
      the county of the hospital nor from a county contiguous to the county of the
      hospital). MAIN RESULTS: Sorting hospitals in descending sequence of numbers of
      surgical cases, depending on year, the top 10% of hospitals performed 58.4% to
      59.2% of the cases. Increases in numbers of cases among patients with commercial
      insurance increased the heterogeneity among hospitals in numbers of surgical
      cases (P < 0.0001). However, the magnitude of the effect was very small, with an
      estimated relative marginal effect on the overall Gini index of only 0.9% +/-
      0.2% (SE). Increases in numbers of cases of patients with Medicare insurance
      reduced the heterogeneity in numbers of cases among hospitals (P < 0.0001), but
      also with very small magnitude (-0.9% +/- 0.2%). In contrast, factors encouraging
      patient travel contributed to larger hospitals becoming larger, and smaller
      hospitals becoming smaller (3.9% +/- 0.7%, P < 0.0001). CONCLUSIONS: We found the
      absence of a substantive effect of insurance and national US payment systems on
      the relative distribution of surgical cases among hospitals. Anesthesia groups
      should focus on payer and payment reform in terms of their effects on payment
      rates (e.g., average payment per relative value guide unit), not on their
      potential effects on hospital caseloads.

PMID- 30099351
TI  - Association between periodic limb movements during sleep and cerebral small
      vessel disease.
AB  - OBJECTIVE: Periodic limb movements (PLMs) can increase the risk of cardiovascular
      disease and mortality. Small vessel disease (SVD) has been considered a precursor
      to symptomatic stroke. We aimed to investigate the association between PLMs and
      cerebral SVD. METHODS: We enrolled participants who visited our clinic for the
      evaluation of sleep disturbance and underwent overnight polysomnography and brain
      magnetic resonance imaging. The processing steps included rating and analyzing
      white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), asymptomatic
      lacunar infarctions (ALIs), perivascular spaces (PVSs), and calculating the total
      SVD score. Logistic regression and correlation analyses were used to examine the
      association between PLMs during sleep (PLMS) and SVD. RESULTS: A total of 31 (19
      men and 12 women) patients with PLMS index >= 15/h were enrolled. The mean age
      was 61.7 years and the median PLMS index was 46.5/h. A total of 29 controls (16
      men and 13 women) with PLMS index < 5/h were also included. PLMS index was
      positively associated with an increase in WMHs, ALIs, and PVSs (odds ratio [OR] =
      1.022, 95% confidence interval [CI] = 1.003-1.040, p = 0.008; OR = 1.024, 95% CI
      = 1.006-1.043, p = 0.010; OR = 1.029, 95% CI = 1.010-1.049, p = 0.003,
      respectively). Correlation analyses revealed that total SVD score was
      significantly correlated with PLMS index (r = 0.504, p < 0.001). CONCLUSIONS: An
      elevated PLMS index was associated with an increase in WMHs, ALIs, PVSs, and
      total SVD burden. Our study suggests that PLMS is a marker for SVD, which carries
      a potential risk for progression to overt stroke or cognitive impairment.

PMID- 30099350
TI  - Impaired cerebral oxygenation and exercise tolerance in patients with severe
      obstructive sleep apnea syndrome.
AB  - OBJECTIVE AND BACKGROUND: Impaired cerebral blood flow and cerebrovascular
      reactivity to hypercapnia during wakefulness at rest as well as reduced exercise
      tolerance have been reported in severe obstructive sleep apnea (OSA) patients.
      Impaired cerebral oxygenation and hemodynamics can contribute to reduced exercise
      performance. We hypothesized that (i) OSA patients show impaired cerebrovascular
      response both during exercise and in response to hypercapnia together with
      reduced exercise tolerance and (ii) continuous positive airway pressure (CPAP)
      treatment improves these alterations in cerebral oxygenation. METHODS: Fifteen
      OSA patients and 12 healthy matched controls performed a hypercapnic response
      test and a maximal cardiopulmonary exercise test before and after eight weeks of
      CPAP treatment or control period. Prefrontal cortex and muscle oxygenation were
      assessed by near-infrared spectroscopy (NIRS) during both tests. RESULTS:
      Cerebrovascular reactivity to hypercapnia was impaired in OSA patients (lower
      increase in oxyhemoglobin [0.29 +/- 0.19 vs 0.44 +/- 0.14 MUmol mmHg-1] and total
      hemoglobin [0.14 +/- 0.15 vs 0.26 +/- 0.09 MUmol mmHg-1]) compared to controls.
      Reduced prefrontal cortex oxygen extraction and total blood volume (ie, lower
      increase in deoxyhemoglobin [1.76 +/- 1.57 vs 3.43 +/- 2.08 MUmol] and total
      hemoglobin [5.36 +/- 7.08 vs 8.55 +/- 5.13 MUmol at exhaustion], respectively)
      during exercise together with a reduced exercise tolerance (ie, lower peak oxygen
      consumption) were observed in OSA patients compared to controls. CPAP treatment
      did not induce any improvement in cerebrovascular response during hypercapnic
      response test and exercise. CONLUSIONS: This study demonstrates that
      cerebrovascular response to exercise is altered in OSA and may contribute to
      exercise intolerance in these patients. Prefrontal cortex oxygenation and
      exercise tolerance are not significantly improved following eight weeks of CPAP
      treatment. CLINICAL TRIAL REGISTRATION: NCT02854280.

PMID- 30099352
TI  - Association of social jetlag with metabolic syndrome among Japanese working
      population: the Furukawa Nutrition and Health Study.
AB  - OBJECTIVE: Social jetlag, ie, the mismatch between biological and social timing,
      has been suggested to induce obesity and cardiometabolic abnormalities. Yet, no
      study has currently linked social jetlag to metabolic syndrome (MetS) among
      Asians. The aim of this study was to investigate the cross-sectional association
      of social jetlag with MetS in a Japanese working population. METHODS:
      Participants were 1164 employees, aged 18-78 years, who completed a health survey
      at a periodic checkup. Social jetlag was calculated as the difference in hours of
      midpoint of sleep times between weekdays and weekends. MetS was defined according
      to the Joint Interim Statement criteria. Multivariable logistic regression was
      used to examine the association between social jetlag and MetS with adjustment
      for potential confounding variables. RESULTS: Greater social jetlag was
      significantly associated with an increased likelihood of having MetS. The
      multivariable adjusted odds ratio (95% confidence intervals) for >=2 h of social
      jetlag was 1.92 (1.01-3.67) compared to those with <1 h of social jetlag. Of the
      components of MetS, greater social jetlag was significantly associated with an
      increased likelihood of having high waist circumference; the multivariable
      adjusted odds ratio (95% confidence intervals) for >=2 h of social jetlag was
      2.26 (1.33-3.84) compared to those with <1 h of social jetlag. CONCLUSION: Social
      jetlag may be associated with an increased likelihood of having MetS among non
      shift workers.

PMID- 30099353
TI  - Association of sleep disorders, chronic pain, and fatigue with survival in
      patients with chronic kidney disease: a meta-analysis of clinical trials.
AB  - OBJECTIVE: Sleep disorders, chronic pain, and fatigue have been long-standing
      torments in most patients with chronic kidney disease (CKD). In this review, we
      attempted to explore whether these nontraditional cardiovascular risk factors are
      associated with increased mortality in patients with CKD. METHOD: Electronic
      searches were performed in MEDLINE (PubMed, 1966-2018), EMBASE (1974-2018),
      ClinicalTrials.gov, and the Cochrane Central Register of Controlled Trials
      databases. All prospective or retrospective studies were considered eligible if
      they were cohort or observational studies and the final outcome was all-cause
      death or mortality. RESULTS: We ultimately included 18 studies (12 studies on
      sleep disorders, three studies on chronic pain, and three studies on fatigue) in
      our review. Pooled analysis of all studies indicated that patients with sleep
      disorders, chronic pain, and fatigue had increased risks of all-cause mortality
      (risk ratio [RR] = 1.47, 95% confidence interval [CI] = 1.30-1.66, p < 0.0001; RR
      = 1.29, 95% CI = 1.27-1.31, p < 0.0001; RR = 1.45, 95% CI = 1.23-1.70, p <
      0.0001, respectively). Pooled results from four studies indicated that dialysis
      patients with sleep-disordered breathing had increased cardiovascular disease
      outcomes (RR = 2.45, 95% CI = 1.74-3.44, p < 0.0001). CONCLUSION: Sleep
      disorders, chronic pain, and fatigue are remarkably associated with increased all
      cause mortality in patients with CKD. Large clinical randomized controlled trials
      are required to further confirm the results of our meta-analysis.

PMID- 30099354
TI  - Sleep assessment in a randomized trial of hyperbaric oxygen in U.S. service
      members with post concussive mild traumatic brain injury compared to normal
      controls.
AB  - STUDY OBJECTIVE: In this exploratory, double-blind, longitudinal sham-controlled
      trial of hyperbaric oxygen (HBO2) for military personnel with post concussive
      mild traumatic brain injury (mTBI), self-reports and objective measures of sleep
      wake disturbances were assessed and compared to normals. METHODS: Self-reports
      consisting of Pittsburg Sleep Quality Index (PSQI), sleep diary, screening for
      obstructive sleep apnea (OSA) risk, restless legs syndrome (RLS), cataplexy, and
      objective actigraphic measures of sleep-wake were obtained on 71 military
      personnel with mTBI [baseline, 13 weeks and six months post-randomization (post
      intervention)], of which 35 met post-traumatic stress disorder (PTSD) criteria,
      and 75 healthy volunteers (baseline). Baseline between-group and follow-up
      changes from baseline overall and within subgroups were evaluated. Mild TBI was
      defined as consisting of head injury associated loss of consciousness (<24 h),
      post-traumatic amnesia, and neurological deficits. RESULTS: Sleep quality by self
      reports was markedly degraded in the mTBI group at baseline compared to a
      normative cohort; insomnia 87.3 versus 2.8%, OSA risk 70% versus 1.3%, RLS 32.4%
      versus and 2.7%. (all p-values <0.001), but actigraphy measures did not
      differentiate between groups. HBO2 compared to sham treatment improved self
      reports of PSQI sleep measures, reports (five out of eight at 13-weeks and two
      out of eight at six-months). However, other sleep-wake measures were not
      different. CONCLUSIONS: Perceived sleep quality was markedly disrupted in mTBI
      military personnel and sleep-wake disturbances were prevalent compared to a
      normative cohort. HBO2 relative to sham improved some measures of sleep quality
      on the PSQI, but other measures of sleep were not significantly different.

PMID- 30099355
TI  - Women with both sleep problems and snoring show objective impairment of sleep.
AB  - OBJECTIVE: Combined insomnia and obstructive sleep apnea has been the focus of
      considerable research with respect to its health effects. A related issue is
      whether sleep disturbances in combination with snoring might exert effects on
      objective sleep variables in the non-clinical general population. The purpose of
      the present study was to investigate the polysomnographical characteristics of
      individuals who had sought medical help for both disturbed sleep and for snoring.
      No previous work of this type has been carried out. METHOD: For this study we
      used a representative set of data of 384 women with one night of in-home PSG. We
      identified those individuals who had sought medical help for sleep problems (SL),
      individuals that had sought help for snoring (SN), as well as those that had
      sought help for either both (Combined), or for neither (Control). RESULTS: Our
      results yielded an N of 46, 16, 21, and 301 individuals, respectively. A one
      factor analysis of variance showed significant main effects on N1% (F = 10.2, p <
      0.001), N3% (F = 2.7, p < 0.05), AHI/h (F = 5.5, p < 0.001), and a delta power
      measure (F = 3.8, p < 0.05). The combined group showed significantly higher
      levels than the other groups for N1% (29% vs < 21%), AHI/h (19/h vs < 10/h) and
      lower levels for N3%, and a measure of delta power. Reported sleep quality
      measures did not show the same pattern, since the highest/lowest value were found
      for either the group presenting snoring alone or sleep problems alone.
      CONCLUSION: We concluded that individuals who had sought help for both insomnia
      and snoring showed impaired sleep in terms of PSG and that this was not reflected
      in ratings of sleep or health. This suggests that simultaneous sleep disturbances
      and snoring may potentiate each other to cause impaired sleep, yet the mechanism
      still needs to be elucidated.

PMID- 30099356
TI  - Antibacterial biocompatible arginine functionalized mono-layer graphene: No more
      risk of silver toxicity.
AB  - Antibacterial ability is vital in biological approaches as well as functional
      biomaterials. Besides, cytocompatibility aspect of biologic media, tissue and
      organs is always concern for appropriate synthesis. From the past, metallic/oxide
      phases of silver (Ag) material in various macro, micro or nano configurations
      have been widely used for antibacterial targets. While, background of Ag toxicity
      within particle, film and composites is posing gradual ion release affected by
      molecular bounding. Recent researches conducted to control, optimize and
      neutralize Ag limitations finding the benefits of ideal (~ 100%) mediation
      against both Gram-negative and Gram-positive bacteria. Whereas, non-degradable
      releases history is still a challenge and its longer accumulation may cause to
      disrupt biostructures and disease risk. Thus, facile development of large-area
      organic materials with switchable bacteria toxicity and normal cell compatibility
      function is interesting for concerned approaches. Here, smart positively-charged
      stable arginine amino acid incorporated mono layer graphene (Arg-EMGr)
      nanobiocomposite introduced as useful antibacterial and safe bactericidal agent
      competitive with Ag direct. The immunity characteristic versus Escherichia coli
      (E. coli) and Staphylococcus aureus (S. aureus) comparably assessed with graphene
      oxide (GO) and different concentrations GO-AgNPs morphology. As cell viability
      matter, 1,3,5,7-days vitro culture assay shown attachment proliferation and
      cytotoxicity due to short interaction.

PMID- 30099357
TI  - Oxidative degradation of Bisphenol A by carbocatalytic activation of persulfate
      and peroxymonosulfate with reduced graphene oxide.
AB  - In the present study, novel metal-free activation of persulfate (PS) and
      peroxymonosulfate with reduced graphene oxide (rGO) was investigated to degrade
      Bisphenol A (BPA), one of the most important endocrine disrupting compounds, from
      different aqueous matrices, namely distilled water (DW) and municipal wastewater
      treatment plant effluent (TWW). The home-made rGO was characterize and the effect
      of oxidant (PS and PMS) and catalyst (rGO) concentrations on BPA degradation
      rates in DW and TWW samples was examined. Complete BPA degradation occurred in DW
      and TWW with the PS/rGO treatment system after 10 min and 30 min, respectively,
      whereas 94% (DW) and 83% (TWW) BPA removals were obtained with PMS/rGO for the
      same treatment period (BPA = 2 mg/L; rGO = 0.02 g/L; PS = 0.25 mM; PMS = 0.5 mM).
      The radical quenching experiments demonstrated that the SO4- predominated in the
      activation of PS and PMS with rGO for BPA removal, however, HO contributed to the
      catalytic oxidation process but to a lower extend. The reusability test results,
      where the catalyst was deactivated seriously just after second cycle, highlighted
      the need for further studies to enhance the stability of rGO. This study
      represented an environmentally benign and efficient oxidative treatment of BPA
      along with insights into the rGO activated PS or PMS processes.

PMID- 30099358
TI  - One-step fabrication of functionalized poly(l-lactide) porous fibers by
      electrospinning and the adsorption/separation abilities.
AB  - In this work, novel functionalized poly(l-lactide) (F-PLLA) porous fibers were
      fabricated through electrospinning using the PLLA/methylene chloride (CH2Cl2)/N,N
      dimethylformamide (DMF) solution containing diethylenetriamine (DETA) and gamma
      aminopropyltriethoxysilane (KH-550). The effects of PLLA, DETA and KH-550
      contents on the morphologies of the electrospun fibers were systematically
      investigated, and the results showed that at PLLA, DETA and KH-550 contents of
      20% w/v, 2 wt% and 3 wt%, respectively, the electrospun F-PLLA fibers exhibited
      the homogeneous distribution of fiber diameters and the homogeneous porous
      structure on the fiber surface. Nitrogen-containing groups were successfully
      introduced to the electrospun fibers, which induced the great improvement of the
      hydrophilicity of the membrane surface. Adsorption measurements showed that the
      electrospun F-PLLA membrane had good adsorption ability toward Congo red (CR),
      and the adsorption capacity at room temperature was enhanced in 16 times compared
      with the common PLLA fiber membrane, and the maximum adsorption capacity was
      135.7 mg g-1. Furthermore, the adsorption behavior could be well described by the
      pseudo second-order model. Oil/water separating measurements showed that the
      electrospun F-PLLA membrane exhibited high separation efficiency and the maximum
      water fluxes were 2018 and 1861 L m-2  h-1 in separating non-emulsified and
      emulsified oil/water system under atmospheric pressure, respectively.

PMID- 30099359
TI  - Polyaniline-derived porous carbons: Remarkable adsorbent for removal of various
      hazardous organics from both aqueous and non-aqueous media.
AB  - Polyaniline (pANI) was pyrolyzed under a nitrogen atmosphere to get porous pANI
      derived carbons (PDCs). To increase the porosity of the carbons further, the PDCs
      were activated at 600-800  degrees C in the presence of KOH. The obtained PDCs
      were firstly applied in liquid-phase adsorptions in order to remove hazardous
      organics from both water and fuel effectively via adsorption. PDC-700, activated
      at 700  degrees C, showed record high adsorption capacities from water for the
      removal of hazardous organics such as diethyl phthalate and Janus Green B, as
      representative organics for industrial chemicals (endocrine disturbing agent) and
      organic dyes, respectively. Moreover, PDC-700 had record high adsorption capacity
      for the removal of 4,6-dimethyldibenzothiophene from a model fuel. The plausible
      mechanisms were also suggested to explain the remarkable adsorptions both from
      water and fuel. The adsorbents could be regenerated in a facile way and reused in
      adsorption up to several cycles. Therefore, the PDCs could be suggested as a new
      class of adsorbents for the purification of both water contaminated with organics
      and fuel having a high concentration of thiophenics.

PMID- 30099360
TI  - Effects of toxin from Bacillus thuringiensis (Bt) on sorption of Pb (II) in red
      and black soils: equilibrium and kinetics aspects.
AB  - Bt crops have been widely commercialized for cultivation in the world, but as
      yet, the effects of Bt toxin on sorption of heavy metals in soils has not been
      reported. In this study, the effects of toxin from Bacillus thuringiensis on Pb
      (II) sorption by red (Ultisol) and black soil (Vertisol) were studied using the
      batch method. The results showed that Pb(II) sorption by both soil types
      decreased in the presence of Bt toxin from 0 to 10 mg/L, which was probably due
      to the sorptive sites competition and Pb-toxin complex formation. The Langmuir
      and Freundlich isotherm models were fitted well to the sorption data at different
      Bt toxin additions. The sorption capacity of black soil for Pb (II) was higher
      than that of red soil, however, the influential trends of Bt toxin to the maximum
      capacity of Pb (II) in both soils was reversed. Sorption of Pb (II) in both soils
      was rapid and reached equilibrium within 80 min, following the pseudo-second
      order kinetic model. Decreasing sorption of Pb (II) by red and black soils was
      observed in the presence of Bt toxin, suggesting that the environmental risk of
      Pb(II) may increase if Bt toxin is released by Bt crops.

PMID- 30099361
TI  - Ultra-low content of Pt modified CdS nanorods: Preparation, characterization, and
      application for photocatalytic selective oxidation of aromatic alcohols and
      reduction of nitroarenes in one reaction system.
AB  - A series of Pt nanoparticles (with size of 3-4 nm) decorated CdS nanorods were
      prepared via a simple solvothermal method. The samples were then used for
      photocatalytic selective oxidation (SO) of aromatic alcohols and reduction (SR)
      of nitroarenes in one reaction system. The platinized samples showed enhanced
      activity for the conversions than pristine CdS as Pt can serve as e- trapping and
      reaction sites, by which the recombination of photoinduced charge carriers can be
      suppressed and the adsorption of reactants and the SR of nitroarenes can be
      promoted. The sample loaded with only of 0.03% Pt showed the highest performance
      and, after irradiation for 4 h, the conversions of p-methoxybenzyl alcohol and
      nitrobenzene are as high as 92.7% and 94.8%, while the yields of p
      methoxybenzaldehyde and aniline are 80.5% and 36.0%. The activities are about 2.0
      times higher than that of CdS. The coupling reaction mechanism for the SO of
      aromatic alcohols to aldehydes and SR of nitroarenes to anilines in the reaction
      system was finally proposed.

PMID- 30099362
TI  - In-situ synthesis of rGO-ZnO nanocomposite for demonstration of sunlight driven
      enhanced photocatalytic and self-cleaning of organic dyes and tea stains of
      cotton fabrics.
AB  - Recently, research activities are focused on development of 2D reduced graphene
      oxide (rGO) based semiconductor nanocomposite materials for boosting up its
      catalytic applications. In this work, a rarely reported green synthesis approach
      has been envisioned to synthesize in-situ 2D rGO-ZnO (rGZn) nanocomposites from
      Apple juice and zinc acetate. Also the composition of the samples has been
      optimized to achieve high photocatalytic and self-cleaning properties by the
      formation of reactive oxidation species. The samples are characterized for their
      microstructural, optical absorption and photoluminescence properties. It has been
      tested that rGZn nanocomposites are capable of removing a test dye, namely
      methylene blue (MB) from water and achieved the highest dye degradation
      efficiency of ~91% within only 60 min under UV-vis light irradiation. A smart
      cotton fabric (CF) coated with rGZn has been prepared and demonstrated its
      photocatalytic self-cleaning property by degradation of MB, rhodamine B dyes and
      tea stains on it even under sunlight irradiation, which is scarcely available in
      the literature. Therefore, this work may open a new avenue of research for low
      cost and easy synthesis of rGO-semiconductor nanocomposites with high
      photocatalytic properties for industrial applications as well as for development
      of rGO based smart fabric for real-life applications.

PMID- 30099363
TI  - Advanced oxidation of pharmaceuticals by the ozone-activated peroxymonosulfate
      process: the role of different oxidative species.
AB  - Given the need for innovations in advanced oxidation processes to deal with
      challenges such as OH scavenging, this paper addresses the removal of
      pharmaceuticals with a large variety in ozone reactivity (kO3 = 0.15-3 * 105 M-1s
      1) by use of the novel ozone-activated peroxymonosulfate (O3/PMS) process. A
      clear improvement in removal efficiency (up to 5 times higher) is noticed as a
      result of the generation of SO4- radicals, mainly for slow-ozone reacting
      compounds (kO3 <= 250 M-1s-1) and in the presence of a OH scavenger. Depending on
      the target compound, SO4- are assessed to contribute for 50-90% to the overall
      removal of the micropollutants, both in single-compound and mixture experiments.
      Ozone-based PMS activation occurs at neutral to alkaline pH and, in the presence
      of a OH scavenger, removal efficiencies during O3/PMS are up to 3 times higher
      than with the O3/H2O2 process. In optimizing the O3/PMS process, a trade-off has
      to made between the desired removal and the PMS:O3 ratio. A molar ratio of 1:10
      already results in a clear benefit compared to the ozonation process. Further
      increase of the PMS content up to a 1:1 ratio improved the removal by an
      additional factor of 1.3-1.5.

PMID- 30099364
TI  - The effect of biochar on the mitigation of the chiral insecticide fipronil and
      its metabolites burden on loach (Misgurnus.anguillicaudatus).
AB  - In this work, the enantioselective toxicity, enrichment, and distribution of
      fipronil and its main metabolites (fipronil sulfone, fipronil sulfide, and
      fipronil desulfinyl) in loach (Misgurnus anguillicaudatus) were studied. The
      influence of maize-straw derived biochar on acute toxicity and bioaccumulation of
      contaminants were also investigated. The three main metabolites were more toxic
      to loach than parent fipronil. Meanwhile, loach exhibited more sensitive to S
      enantiomer. The alleviated toxic response of loach was observed in the presence
      of biochar during 72-h acute toxicity test. Fipronil was readily metabolized to
      sulfone and sulfide with enantioselectivity in loach liver, and it was also found
      R-fipronil could transform into S-fipronil. The metabolites profile indicated
      that oxidation processes was the most predominant pathway in loach.
      Bioaccumulation factors showed the metabolites could be enriched in loach and
      they were relatively persistent. The bioaccessibility of fipronil and its
      metabolite decreased significantly when biochar was applied to the ecosystem. The
      present study provided basic data and outlines of enantioselective toxicity,
      biotransformation and metabolism of chiral pesticide fipronil and its main
      derivatives along with biochar in loach-water ecosystem, and further provide an
      alternative approach for field remediation to mitigate environmental adverse
      effects of fipronil.

PMID- 30099366
TI  - Notes From the Other Side.

PMID- 30099365
TI  - Beyond unpleasantness. Social exclusion affects the experience of pain, but not
      of equally-unpleasant disgust.
AB  - Seminal theories posit that social and physical suffering underlie partly-common
      representational code. It is unclear, however, if this shared information
      reflects a modality-specific component of pain, or alternatively a supramodal
      code for properties common to many aversive experiences (unpleasantness,
      salience, etc.). To address this issue, we engaged participants in a gaming
      experience in which they were excluded or included by virtual players. After each
      game session, participants were subjected to comparably-unpleasant painful or
      disgusting stimuli. Subjective reports and cardiac responses revealed a reduced
      sensitivity to pain following exclusion relative to inclusion, an effect which
      was more pronounced in those participants who declared to feel more affected by
      the gaming manipulation. Such modulation was not observed for disgust. These
      findings indicate that the relationship between social and physical suffering
      does not generalize to disgust, thus suggesting a shared representational code at
      the level of modality-specific components of pain.

PMID- 30099367
TI  - Letter to the Editor: Integrating Skeletal Muscle Mass and Radiodensity Improves
      Outcome Prediction and Correlation in Oncologic Studies.

PMID- 30099368
TI  - Evaluating Antiretroviral Therapy Initiation in HIV-Associated Malignancy: Is
      There Enough Evidence to Inform Clinical Guidelines?

PMID- 30099369
TI  - DNA Repair Gene Alterations and PARP Inhibitor Response in Patients With
      Metastatic Castration-Resistant Prostate Cancer.
AB  - Background: PARP inhibition is a promising therapeutic strategy for the treatment
      of men with metastatic castration-resistant prostate cancer whose tumors harbor
      homologous recombination DNA repair gene alterations. However, questions remain
      for many practicing clinicians about which patients are ideally suited for PARP
      inhibitor treatment. This report details our institutional experience using PARP
      inhibitor therapy in patients whose tumors harbored specific DNA repair gene
      alterations. Patients and Methods: We performed a retrospective chart review to
      identify patients at Oregon Health & Science University who were treated with
      PARP inhibition. We identified 8 patients and determined the impact of the
      specific DNA repair gene alterations on tumor response and time on treatment with
      PARP inhibition. Results: A number of DNA repair gene alterations were
      identified. Three patients had pathogenic BRCA2 mutations and one had a BRCA2
      mutation of uncertain significance. Conversely, the 4 other patients' tumors
      harbored alterations in other DNA repair genes, none of which were clearly
      pathogenic. A statistically significant difference in benefit was seen between
      patients whose tumors harbored BRCA2 gene alterations and those whose tumors did
      not, as measured by >50% decline in prostate-specific antigen levels (100% vs 0%;
      P=.03) and duration on therapy (31.4 vs 6.4 weeks; P=.03). Conclusions: Our
      results demonstrate that not all DNA repair alterations are equally predictive of
      PARP inhibitor response. Importantly, all responding patients had tumors
      harboring BRCA2 DNA repair alterations, including one without a known pathogenic
      mutation. Conversely, among the 4 nonresponders, several DNA repair alterations
      in genes other than BRCA2 were identified that were not clearly pathogenic. This
      demonstrates the need to carefully examine the functional relevance of the DNA
      repair alterations identified, especially in genes other than BRCA2, when
      considering patients for PARP inhibitor treatment.

PMID- 30099371
TI  - Chemoradiation Improves Survival Compared With Chemotherapy Alone in Unresected
      Nonmetastatic Gastric Cancer.
AB  - Background: Limited data are available to guide management of patients with stage
      I-III gastric cancer not undergoing potentially curative surgical resection. We
      compared survival outcomes associated with chemotherapy alone versus
      chemoradiation (CRT) in the treatment of nonmetastatic gastric cancer. Methods:
      Patients with gastric adenocarcinoma from 2004 to 2015 were identified using the
      National Cancer Database. Patients were excluded if they had surgery, metastatic
      disease, or T0, Tis, or T1a disease. Logistic regression was used to evaluate
      predictors of CRT use. Cox proportional hazards modeling was performed to compare
      overall survival (OS) between chemotherapy alone and CRT in overall and
      propensity score-matched cohorts. Results: We identified 4,795 patients with
      stage I-III gastric adenocarcinoma who did not undergo surgery, at a median
      follow-up of 11.8 months. A total of 3,316 patients (69.2%) received chemotherapy
      alone and 1,479 patients (30.8%) received CRT. Predictors of increased CRT use
      were age >=65 years (odds ratio [OR] 1.68; 95% CI, 1.43-1.99; P<.001), Charlson
      Deyo comorbidity score >=2 (OR, 1.46; 95% CI, 1.18-1.81), and treatment at a
      community facility (OR, 1.27; 95% CI, 1.07-1.51; P=.006). Patients receiving CRT
      had a 2-year OS rate of 28.3% compared with 21.5% among those receiving
      chemotherapy. Multivariate analysis showed that CRT was associated with improved
      OS (hazard ratio [HR], 0.82; 95% CI, 0.77-0.89; P<.001). After propensity score
      matching, a persistent survival benefit was observed (HR, 0.80; 95% CI, 0.74
      0.88; P<.001). Conclusions: In patients with stage I-III gastric cancer not
      undergoing surgical resection, CRT was associated with improved survival compared
      with chemotherapy alone. However, only 30.8% of patients received CRT in this
      setting.

PMID- 30099370
TI  - NCCN Guidelines Insights: Colorectal Cancer Screening, Version 1.2018.
AB  - The NCCN Guidelines for Colorectal Cancer (CRC) Screening outline various
      screening modalities as well as recommended screening strategies for individuals
      at average or increased-risk of developing sporadic CRC. The NCCN panel meets at
      least annually to review comments from reviewers within their institutions,
      examine relevant data, and reevaluate and update their recommendations. These
      NCCN Guidelines Insights summarize 2018 updates to the NCCN Guidelines, with a
      primary focus on modalities used to screen individuals at average-risk for CRC.

PMID- 30099373
TI  - Genomic Profiling in Patients With Malignant Peripheral Nerve Sheath Tumors
      Reveals Multiple Pathways With Targetable Mutations.
AB  - Background: The aim of this study was to determine the frequency of alterations
      in BRAF and other RAS/RAF genes, as well as other targetable pathways in
      malignant peripheral nerve sheath tumors (MPNSTs). Patients and Methods:
      Pathology specimens were available for 2 cohorts: (1) patients with MPNST at
      Swedish Cancer Institute (n=17) from 2004 through 2016, and (2) patients with
      MPNST evaluated for >300 genomic alterations at Foundation Medicine from 2014
      through 2016 (n=186; including 2 Swedish patients with BRAF-mutated MPNST).
      Results: Of 201 MPNSTs, 13 (6.5%) demonstrated BRAF alterations. In the
      Foundation Medicine cohort, 10 of 84 tumors (11.9%) with no NF1 alterations had
      BRAF mutations (5 were V600E, 5 other), as did 3 of 102 (2.9%) tumors with NF1
      alterations (1 V600E, 2 other). In the Foundation Medicine cohort, 47% of
      patients had an alteration in at least one other gene in the RAS/RAF pathway (not
      including NF1 or BRAF); 46% had alterations in the PI3 pathway, with 70% having
      alterations in at least 1 of the 2 pathways; 57% had a CDKN2A alteration (80% in
      BRAF-mutated and 71% in NF1-altered patients); and 70% had an alteration in DNA
      repair genes. MPNST, both NF1 wild-type and NF1-mutated, often harbor alterations
      in the RAS/RAF pathway as well as changes related to DNA repair and CDKN2A/B
      V600E and other mutations occur in BRAF, suggesting the need for second
      generation activating BRAF inhibitors. The concurrence of BRAF and/or NF1
      alterations with CDKN2A/B mutations, in particular, may be significant in the
      transformation of neurologic tumors from benign to malignant. Conclusions: All
      MPNSTs would benefit from a comprehensive genomic analysis. Treatments targeted
      to RAS/RAF, DNA repair, and CDKN2A/B pathways should be used and/or developed to
      treat this uncommon tumor.

PMID- 30099372
TI  - Swedish Version of the Distress Thermometer: Validity Evidence in Patients With
      Colorectal Cancer.
AB  - Background: The objective of this study was to validate the NCCN Distress
      Thermometer (DT), including the accompanying Problem List (PL), in a Swedish
      population of patients diagnosed with colorectal cancer (CRC). Methods: A total
      of 488 patients diagnosed with CRC completed the DT/PL and EORTC core quality-of
      life questionnaire (QLQ-C30) before surgery. Construct validity of the PL was
      analyzed using a confirmatory factor analysis. Internal consistency reliability
      (ICR) was tested using Cronbach's alpha coefficient. Correlations between the
      reported PL areas and QLQ-C30 function scales were used to explore convergent
      validity. Discriminant validity was examined by evaluating associations between
      the DT and QLQ-C30 measures of overall health-related quality of life (HRQoL).
      Results: Findings showed that the Swedish translation of the DT/PL is consistent
      with the original English version. The DT has good ICR, with the total number of
      reported problems significantly correlating with DT scores (r=0.67; P<.001).
      Analysis of convergent validity indicated that the PL areas significantly
      correlated with QLQ-C30 function scales, with emotional problems showing the
      highest correlation (r=0.76; P<.001), and item-level correlation analyses showed
      significant correlations between symptoms. There was also good discriminant
      validity between the DT and the QLQ-C30 in terms of HRQoL, including overall
      health status (r=-0.49; P<.001) and overall quality of life (r=-0.57; P<.001).
      Furthermore, there was good discriminant validity between the DT and QLQ-C30
      regarding poor, moderate, and excellent HRQoL. Conclusions: These findings
      provide validity evidence regarding the DT, including the PL. Findings also show
      that the DT has good potential for screening distress-related practical, family,
      emotional, and physical problems during the cancer trajectory in Swedish-speaking
      patients. Additionally, the DT seems to be an effective screening tool to detect
      patients with poor, moderate, and excellent HRQoL.

PMID- 30099374
TI  - Determinants and Outcomes of Satisfaction With Healthcare Provider Communication
      Among Cancer Survivors.
AB  - Background: Despite the surge of interest in improving provider communication,
      empirical research is sparse on the determinants and outcomes of cancer
      survivors' satisfaction with healthcare provider communication. Methods:
      Longitudinal Medical Expenditure Panel Survey data spanning 2008 through 2014 was
      used to identify 4,588 respondents who were ever diagnosed with cancer. A
      composite score was generated by combining 5 measures of satisfaction. We used
      multivariate logistic regressions and 2-part models to examine the associations
      between satisfaction ratings and outcomes, including general, mental, and
      physical health; office visits; and total healthcare, drug, and out-of-pocket
      expenditures. Results: The study sample comprised 2,257 nonelderly (age 18-64
      years) and 2,331 elderly (age >=65 years) respondents. Among both age groups,
      higher satisfaction was associated with fewer comorbidities, fewer year 1 office
      visits, and absence of year 1 emergency department visits. Membership of higher
      satisfaction tertile in year 1 was associated with better year 2 mental health
      (tertile 1 [T1]: predictive margin [PM], 27.1%; tertile 2 [T2]: PM, 35.5%;
      P=.013; tertile 3 [T3]: PM, 37.0%; P=.005) and general health (T1 [ref]: PM,
      30.3%; T3: PM, 38.9%; P=.007) among the elderly. Greater satisfaction was
      associated with fewer year 2 office visits (T1 [ref]: PM, 7.42 visits; T3: PM,
      6.26 visits; P=.038) among the nonelderly; and lower year 2 healthcare
      expenditures (T1 [ref]: PM, $34,071; T3: PM, $26,995; P=.049) among the elderly.
      Conclusions: We identified potential differences in cancer survivors' needs and
      expectations of provider communication based on comorbidities and baseline
      service use. These results emphasize the need for individualized communication
      strategies for patients with cancer and survivors shaped by their distinct
      requirements. Our findings of better health, lower service use, and lower
      expenditures among more satisfied cancer survivors suggest that interventions to
      improve provider communication could lead to a more efficient use of healthcare
      resources.

PMID- 30099375
TI  - Cancer in People Living With HIV, Version 1.2018, NCCN Clinical Practice
      Guidelines in Oncology.
AB  - People living with HIV (PLWH) are diagnosed with cancer at an increased rate over
      the general population and generally have a higher mortality due to delayed
      diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer
      treatment disparities. Lack of guidelines and provider education has led to
      substandard cancer care being offered to PLWH. To fill that gap, the NCCN
      Guidelines for Cancer in PLWH were developed; they provide treatment
      recommendations for PLWH who develop non-small cell lung cancer, anal cancer,
      Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline
      advice regarding HIV management during cancer therapy; drug-drug interactions
      between antiretroviral treatments and cancer therapies; and workup, radiation
      therapy, surgical management, and supportive care in PLWH who have cancer.

PMID- 30099377
TI  - Does Chemoradiation Benefit Patients With Gastric Cancer Managed Without Surgery?

PMID- 30099376
TI  - Evolving Paradigms in HIV Malignancies: Review of Ongoing Clinical Trials.
AB  - This review highlights current interventional clinical trials for HIV-associated
      malignancies (HIVAMs), with emphasis on 4 mechanistic areas: immunomodulatory
      therapies and gene therapies, including immune checkpoint inhibitors; cytotoxic
      therapies; novel tumor-targeted and virally targeted therapies in both AIDS
      defining and non-AIDS-defining cancers (NADC); and other screening or
      topical/ablative interventions. A search on ClinicalTrials.gov located 35 trials,
      including 12 immunomodulatory or gene therapy trials, 6 cytotoxic therapy trials,
      10 trials of therapies with tumor or viral molecular targets, and 7 trials
      evaluating screening interventions or topical or ablative therapies. Study drugs,
      mechanisms, and outcomes of interest, including future directions, are discussed.
      Targeted therapies and immunotherapies address not only the tumor but underlying
      viral oncogens, including possible benefits on HIV-specific immunologic control.
      The resulting science from the trials listed in this review will provide
      important translational breakthroughs for people living with HIV (PLWH) and
      cancer. We highlight disease-specific challenges that could be addressed in
      future studies, including testing the safety and efficacy of cutting-edge
      immunotherapy and targeted treatments used in the general cancer population, and
      improving gaps in knowledge and practice for cancer screening and its treatment,
      especially in low-resource regions. Additional important considerations include
      identification of novel therapies for virally mediated tumors that
      disproportionally present in PLWH, how to treat persons with HIVAM and advanced
      immunosuppression, and how to comanage both diseases in antiretroviral therapy
      naive persons and those receiving care in settings where supportive therapies for
      hematologic toxicities and infections are limited. Current and future clinical
      trials should address needs of both resource-replete and -limited regions, as
      well as cancers that are uncommon in or respond differently to HIV-negative
      populations (eg, Kaposi sarcoma or anal cancer), in addition to an increased
      focus on NADCs not traditionally linked with HIV, such as lung or
      gastrointestinal tumors.

PMID- 30099380
TI  - Heat Trims the Fat: HIL1 Functions in Lipid Homeostasis.

PMID- 30099381
TI  - CDL1-OST1 Interaction as a Focal Point of Brassinosteroid-Abscisic Acid Hormone
      Signaling Crosstalk.

PMID- 30099379
TI  - Safety of 5914 intravitreal ziv-aflibercept injections.
AB  - PURPOSE: To analyse the pooled safety data of intravitreal ziv-aflibercept (IVZ)
      therapy for various retinal conditions. METHODS: This was a retrospective,
      observational study which included patients from 14 participating centres who
      received IVZ. The medical records of patients who received IVZ from March 2015
      through October 2017 were evaluated. Patient demographics and ocular details were
      compiled. Ocular and systemic adverse events that occurred within 1 month of IVZ
      injections were recorded and defined as either procedure-related or drug-related.
      RESULTS: A total of 1704 eyes of 1562 patients received 5914 IVZ injections
      (mean+/-SD: 3.73+/-3.94) during a period of 2.5 years. The age of patients was
      60.6+/-12.8 years (mean+/-SD) and included diverse chorioretinal pathologies.
      Both ocular (one case of endophthalmitis, three cases of intraocular
      inflammation, and one case each of conjunctival thinning/necrosis and scleral
      nodule) and systemic adverse events (two cases of myocardial infarction, one case
      of stroke and two deaths) were infrequent. CONCLUSION: This constitutes the
      largest pooled safety report on IVZ use and includes patients from 14 centres
      distributed across the globe. It shows that IVZ has an acceptable ocular and
      systemic safety profile with incidences of adverse events similar to those of
      other vascular endothelial growth factor inhibitory drugs. The analysis supports
      the continued use of IVZ in various retinal disorders.

PMID- 30099382
TI  - Escape from Centromere Land.

PMID- 30099383
TI  - NAC Transcription Factors ANAC087 and ANAC046 Control Distinct Aspects of
      Programmed Cell Death in the Arabidopsis Columella and Lateral Root Cap.
AB  - Programmed cell death in plants occurs both during stress responses and as an
      integral part of regular plant development. Despite the undisputed importance of
      developmentally controlled cell death processes for plant growth and
      reproduction, we are only beginning to understand the underlying molecular
      genetic regulation. Exploiting the Arabidopsis thaliana root cap as a cell death
      model system, we identified two NAC transcription factors, the little
      characterized ANAC087 and the leaf-senescence regulator ANAC046, as being
      sufficient to activate the expression of cell death-associated genes and to
      induce ectopic programmed cell death. In the root cap, these transcription
      factors are involved in the regulation of distinct aspects of programmed cell
      death. ANAC087 orchestrates postmortem chromatin degradation in the lateral root
      cap via the nuclease BFN1. In addition, both ANAC087 and ANAC046 redundantly
      control the onset of cell death execution in the columella root cap during and
      after its shedding from the root tip. Besides identifying two regulators of
      developmental programmed cell death, our analyses reveal the existence of an
      actively controlled cell death program in Arabidopsis columella root cap cells.

PMID- 30099385
TI  - B-BOX DOMAIN PROTEIN28 Negatively Regulates Photomorphogenesis by Repressing the
      Activity of Transcription Factor HY5 and Undergoes COP1-Mediated Degradation.
AB  - Plants have evolved a delicate molecular system to fine-tune their growth and
      development in response to dynamically changing light environments. In this
      study, we found that BBX28, a B-box domain protein, negatively regulates
      photomorphogenic development in a dose-dependent manner in Arabidopsis thaliana
      BBX28 interferes with the binding of transcription factor HY5 to the promoters of
      its target genes through physical interactions, thereby repressing its activity
      and negatively affecting HY5-regulated gene expression. In darkness, BBX28
      associates with CONSTITUTIVELY PHOTOMORPHOGENIC1 (COP1) and undergoes COP1
      mediated degradation via the 26S proteasome system. Collectively, these results
      demonstrate that BBX28 acts as a key factor in the COP1-HY5 regulatory hub by
      maintaining proper HY5 activity to ensure normal photomorphogenic development in
      plants.

PMID- 30099387
TI  - Concomitant acute stroke, pulmonary and myocardial infarction due to in-transient
      thrombus across a patent foramen ovale.
AB  - Non-atherosclerotic myocardial infarction (MI) is an important but often
      misdiagnosed cause of acute MI. Furthermore, non-atherosclerotic MI with
      concomitant acute stroke and pulmonary embolism due to in-transit thrombus across
      a patent foramen ovale (PFO) is a rare but potentially fatal combination (1-3).
      Early detection of this clinical entity can facilitate delivery of targeted
      therapies and avoid poor outcome (1, 2). Here, we describe a 68-year-old female
      with hypertension, tobacco abuse, and chronic obstructive pulmonary disease
      presenting with facial droop, right arm weakness and aphasia. Head computed
      tomography (CT) without contrast was unremarkable. ECG showed an acute
      inferolateral ST-elevation MI (Panel A). As patient presented with both an acute
      neurological deficit and MI, clinical suspicion of non-atherosclerotic MI was
      raised and the patient underwent concurrent emergency coronary angiography (CAG)
      and transesophageal echocardiogram (TEE). TEE revealed highly mobile mass in the
      left and right atrium (Panel B, Video S1). The large mass (thrombus or cast of a
      deep venous thrombus) was caught in a PFO (Panel C-E, Videos S2-3). A second
      smaller mass/thrombus was seen on the Eustachian valve near the right
      atrial/inferior vena cava junction (Panel F, Video S4). CAG confirmed a 100%
      occluded distal right posterolateral artery suggestive of an embolic phenomenon.
      The patient underwent successful thrombectomy, retrieving a large thrombus burden
      (Panel G, Videos S5-7). CT angiography showed occluded internal carotid artery
      (Panel H). Pathology from thrombectomy confirmed fibrin-rich thrombus. The
      patient had bilateral lower extremity deep vein thrombosis and bilateral diffuse
      pulmonary embolisms.

PMID- 30099386
TI  - Trans-oesophageal echocardiography (TOE): contra-indications, complications and
      safety of perioperative TOE.
AB  - Trans-oesophageal echocardiography (TOE) has become an almost universal
      intraoperative monitor and diagnostic tool. The use of TOE in most cardiac,
      aortic, major vascular and transplant operations is used to aid anaesthetic
      management as well as assist surgical decision-making. In addition to the
      perioperative environment it is increasingly being used in the Outpatient
      Department, Emergency Department and Intensive Care settings. In this review we
      consider the safety associated with the use of TOE, we review the suggested
      contra-indications and areas that we would consider to TOE to be a necessity. Two
      case reports at the beginning of the review highlight the need for vigilance and
      care when utilizing TOE.

PMID- 30099388
TI  - The use of Apixaban for the treatment of an LV thrombus.
AB  - A 42 year old male was admitted with shortness of breath secondary to suspected
      heart failure and chest infection. An echocardiogram revealed a dilated and
      impaired left ventricle; ejection fraction 29%, with a large, mobile thrombus
      within the left ventricular apex. Due to the presence of liver dysfunction,
      vitamin K antagonists were deemed inappropriate, thus the decision was taken to
      use the novel anticoagulation agent Apixaban. After six days of receiving
      Apixaban, a cardiac magnetic resonance scan was preformed which showed complete
      resolution of the LV apical thrombus.

PMID- 30099384
TI  - Plastidial Phosphoglucose Isomerase Is an Important Determinant of Seed Yield
      through Its Involvement in Gibberellin-Mediated Reproductive Development and
      Storage Reserve Biosynthesis in Arabidopsis.
AB  - The plastid-localized phosphoglucose isomerase isoform PGI1 is an important
      determinant of growth in Arabidopsis thaliana, likely due to its involvement in
      the biosynthesis of plastidial isoprenoid-derived hormones. Here, we investigated
      whether PGI1 also influences seed yields. PGI1 is strongly expressed in maturing
      seed embryos and vascular tissues. PGI1-null pgi1-2 plants had ~60% lower seed
      yields than wild-type plants, with reduced numbers of inflorescences and thus
      fewer siliques and seeds per plant. These traits were associated with low
      bioactive gibberellin (GA) contents. Accordingly, wild-type phenotypes were
      restored by exogenous GA application. pgi1-2 seeds were lighter and accumulated
      ~50% less fatty acids (FAs) and ~35% less protein than wild-type seeds. Seeds of
      cytokinin-deficient plants overexpressing CYTOKININ OXIDASE/DEHYDROGENASE1
      (35S:AtCKX1) and GA-deficient ga20ox1 ga20ox2 mutants did not accumulate low
      levels of FAs, and exogenous application of the cytokinin 6-benzylaminopurine and
      GAs did not rescue the reduced weight and FA content of pgi1-2 seeds. Seeds from
      reciprocal crosses between pgi1-2 and wild-type plants accumulated wild-type
      levels of FAs and proteins. Therefore, PGI1 is an important determinant of
      Arabidopsis seed yield due to its involvement in two processes: GA-mediated
      reproductive development and the metabolic conversion of plastidial glucose-6
      phosphate to storage reserves in the embryo.

PMID- 30099389
TI  - Cancer and suicidal ideation and behaviours: protocol for a systematic review and
      meta-analysis.
AB  - INTRODUCTION: Prevalence of suicidal ideation (SI) and behaviours are higher
      among patients with cancer than general population. No systematic review/meta
      analysis investigated this topic; therefore, our aim will be to assess the
      relationship between cancer and SI and behaviours. METHODS: We will search
      PubMed/MEDLINE, EMBASE, SCOPUS, Web of Science, PsycINFO and Cochrane Library
      databases from their inception until 30 June 2018. Case-control and cohort
      studies focused on the association between cancer (any type) and suicidal
      outcomes (suicide, suicide attempt and SI) will be included. Two team members
      will independently: (A) perform the selection of the included studies and data
      extraction, with the supervision of a third member in case of discrepancies and
      (B) assess each study with: (1) Newcastle-Ottawa Scale (NOS); (2) Strengthening
      the Reporting of Observational Studies in Epidemiology (STROBE) statement; (3)
      Grading of Recommendations Assessment, Development and Evaluation (GRADE). We
      will conduct a random-effects meta-analysis. Individual and pooled ORs and
      associated 95% CIs will be calculated as well as between-study heterogeneity. We
      will examine the potential for publication bias. If possible, we will explore
      reasons for potential between-study heterogeneity. ETHICS AND DISSEMINATION: This
      study does not require ethical approval. The study will be submitted to a peer
      reviewed journal, will be publicly disseminated and will be the topic of research
      presentations. PROSPERO REGISTRATION NUMBER: CRD42017072482.

PMID- 30099390
TI  - Combining online Community Reinforcement and Family Training (CRAFT) with a
      parent-training programme for parents with partners suffering from alcohol use
      disorder: study protocol for a randomised controlled trial.
AB  - INTRODUCTION: Partners and children of individuals with alcohol use disorder
      (AUD) present with impaired quality of life and mental health, yet seldom seek or
      participate in traditional supportive interventions. Engaging the parent/partner
      without AUD in treatment is a promising way of supporting behavioural change in
      both the child and the parent with AUD. Universal parent-training (PT) programmes
      are effective in increasing children's well-being and decreasing problem
      behaviours, but have yet to be tailored for children with a parent with AUD.
      Community Reinforcement Approach And Family Training (CRAFT) programmes are
      conceptually similar, and aim to promote behavioural change in individuals with
      AUD by having a concerned significant other change environmental contingencies.
      There has been no study on whether these two interventions can be combined and
      tailored for partners of individuals with AUD with common children, and delivered
      as accessible, online self-help. METHODS AND ANALYSIS: n=300 participants with a
      child showing mental health problems and partner (co-parent) with AUD, but who do
      not themselves present with AUD, will be recruited from the general public and
      randomised 1:1 to either a four-module, online combined PT and CRAFT programme or
      a psychoeducation-only comparison intervention. Primary outcome will be the
      child's mental health. Additional outcomes will cover the partner's drinking, the
      participants own mental health and drinking, the child's social adjustment,
      treatment seeking in all three parties and parental self-efficacy. Measures will
      be collected preintervention, mid-intervention and postintervention, and three
      times during a 2-year follow-up period. Data will be analysed using mixed-effects
      modelling. ETHICS AND DISSEMINATION: This study has been approved by the
      Stockholm Regional Ethical Review Board (2016/2179-31). The results will be
      presented at conferences and published as peer-reviewed publications. TRIAL
      REGISTRATION NUMBER: ISRCTN38702517; Pre-results.

PMID- 30099391
TI  - Binational cohort study comparing the management and outcomes of pregnant women
      with a BMI >50-59.9 kg/m2 and those with a BMI >=60 kg/m2.
AB  - OBJECTIVES: To compare the management, maternal and perinatal outcomes of women
      with a body mass index (BMI) >=60 kg/m2 with women with a BMI >50-59.9 kg/m2.
      DESIGN: International collaborative cohort study. SETTING: Binational study in
      the UK and Australia. PARTICIPANTS: UK: all pregnant women, and Australia: women
      who gave birth (birth weight >=400 g or gestation >=20 weeks) METHODS: Data from
      the Australasian Maternity Outcomes Surveillance System and UK Obstetric
      Surveillance System. Management, maternal and infant outcomes were compared
      between women with a BMI >=60 kg/m2 and women with a BMI >50-59.9 kg/m2, using
      unconditional logistic regression. RESULTS: The sociodemographic characteristics
      and previous medical histories were similar between the 111 women with a BMI >=60
      kg/m2 and the 821 women with a BMI >50-59.9 kg/m2. Women with a BMI >=60 kg/m2
      had higher odds of thromboprophylaxis usage in both the antenatal (24% vs. 12%;
      OR 2.25, 95% CI 1.39 to 3.64) and postpartum periods (78% vs. 66%; OR 1.68, 95%
      CI 1.04 to 2.70). Women with BMI >=60 kg/m2 had nearly double the odds of pre
      eclampsia/eclampsia (adjusted OR 1.83 (95% CI 1.01 to 3.30)). No other maternal
      or perinatal outcomes were statistically significantly different. Severe adverse
      outcomes such as perinatal death were uncommon in both groups thus limiting the
      power of these comparisons. The rate of perinatal deaths was 18 per 1000 births
      for those with BMI >=60 kg/m2; 12 per 1000 births for those with BMI >50-59.9
      kg/m2; those with BMI >=60 kg/m2 had a non-significant increased odds of
      perinatal death (unadjusted OR 1.46, 95% CI 0.31 to 6.74). CONCLUSIONS: Women are
      managed differently on the basis of BMI even at this extreme as shown by
      thromboprophylaxis. The pre-eclampsia result suggests that future research should
      examine whether weight reduction of any amount prior to pregnancy could reduce
      poor outcomes even if women remain extremely obese.

PMID- 30099392
TI  - Electronic patient-generated health data to facilitate prevention and health
      promotion: a scoping review protocol.
AB  - INTRODUCTION: Rapidly expanding digital innovations transform the perception,
      reception and provision of health services. Simultaneously, health system
      challenges underline the need for patient-centred, empowering and citizen
      engaging care, which facilitates a focus on prevention and health promotion.
      Through enhanced patient-engagement, patient-provider interactions and reduced
      information gaps, electronic patient-generated health data (PGHD) may facilitate
      both patient-centeredness and preventive scare. Despite that, comprehensive
      knowledge syntheses on their utilisation for prevention and health promotion
      purposes are lacking. The review described in this protocol aims to fill that
      gap. METHODS AND ANALYSIS: Our methodology is guided by Arksey and O' Malley's
      methodological framework for scoping reviews, as well as its advanced version by
      Levac, Colquhoun and O'Brien. Seven electronic databases will be systematically
      searched using predefined keywords. Key electronic journals will be hand
      searched, while reference lists of included documents and grey literature sources
      will be screened thoroughly. Two independent reviewers will complete study
      selection and data extraction. One of the team's senior research members will act
      as a third reviewer and make the final decision on disputed documents. We will
      include literature with a focus on electronic PGHD and linked to prevention and
      health promotion. Literature on prevention that is driven by existing discomfort
      or disability goes beyond the review's scope and will be excluded. Analysis will
      be narrative and guided by Shapiro et al's adapted framework on PGHD flow. ETHICS
      AND DISSEMINATION: The scoping review described in this protocol aims to
      establish a baseline understanding of electronic PGHD generation, collection,
      communication, sharing, interpretation, utilisation, context and impact for
      preventive purposes. The chosen methodology is based on the use of publicly
      available information and does not require ethical approval. Review findings will
      be disseminated in digital health conferences and symposia. Results will be
      published and additionally shared with relevant local and national authorities.

PMID- 30099394
TI  - Evaluation of capillary pathologies by nailfold capillaroscopy in patients with
      psoriasis vulgaris: study protocol for a prospective, controlled exploratory
      study.
AB  - INTRODUCTION: Psoriasis vulgaris was shown to be an independent factor increasing
      the risk of several comorbidities such as obesity, diabetes and dyslipidaemia
      with an increased risk of stroke and myocardial infarction. We hypothesise that
      early endothelial dysfunction, which plays a crucial role in the pathogenesis of
      atherosclerosis, may be detected by digital video nailfold capillaroscopy (DVNC)
      at the level of the dermal capillary microvasculature as a surrogate parameter.
      Nailfolds represent the only body site allowing for a non-invasive assessment of
      the capillary microvasculature at a horizontal plane. DVNC is a well-established
      diagnostic tool for in vivo assessment of the peripheral microcirculation by
      evaluating the morphology of dermal papillary capillaries. To date, reports on
      morphological changes of the non-lesional nailfold capillaries in patients with
      psoriasis vulgaris are scarce and the existing data are not conclusive. METHODS
      AND ANALYSIS: This is a prospective, single-centre, non-randomised, controlled,
      exploratory study assessing the capillary patterns in 100 subjects affected by
      psoriasis vulgaris. Non-lesional nailfold capillaries will be imaged by means of
      DVNC (Optilia Digital Capillaroscopy System, Optilia Instruments AB, Sollentuna,
      Sweden) in 50 patients affected by psoriasis vulgaris and 50 healthy controls.
      Assessments will include a qualitative, descriptive analysis of the nailfold
      capillaries' morphology, as well as a quantitative investigation (frequency,
      extent) of changes in capillary patterns. Moreover, patients' characteristics
      associated with the manifestation of nailfold capillaries' pathologies including
      well-known cardiovascular risk markers will be studied. ETHICS AND DISSEMINATION:
      Ethical approval was provided by the ethic committee of the medical faculty of
      the University of Heidelberg (Ethics approval number S-447/2017). The design and
      the final results of the study will be published and made available to the
      public. TRIAL REGISTRATION NUMBER: DRKS00012856.

PMID- 30099395
TI  - Morita Therapy for depression (Morita Trial): a pilot randomised controlled
      trial.
AB  - OBJECTIVE: To address uncertainties prior to conducting a fully powered
      randomised controlled trial of Morita Therapy plus treatment as usual (TAU)
      versus TAU alone, or to determine that such a trial is not appropriate and/or
      feasible. DESIGN: Pilot parallel group randomised controlled feasibility trial.
      SETTING AND PARTICIPANTS: Participants aged >=18 years with Diagnostic and
      Statistical Manual of Mental Disorders (DSM)-IV major depressive disorder, with
      or without DSM-IV anxiety disorder(s), recruited from general practice record
      searches in Devon, UK. INTERVENTIONS: We randomised participants on a 1:1 basis
      stratified by symptom severity, concealing allocation using a secure independent
      web-based system, to receive TAU (control) or 8-12 sessions of Morita Therapy, a
      Japanese psychological therapy, plus TAU (intervention). OUTCOMES: Rates of
      recruitment, retention and treatment adherence; variance and estimated between
      group differences in follow-up scores (on the Patient Health Questionnaire 9 (PHQ
      9) (depressive symptoms); Generalised Anxiety Disorder Questionnaire 7 (anxiety
      symptoms); Short Form 36 Health Survey Questionnaire/Work and Social Adjustment
      Scale (quality of life); Morita Attitudinal Scale for Arugamama (attitudes)) and
      their correlation with baseline scores. RESULTS: We recruited 68 participants,
      5.1% (95% CI 3.4% to 6.6%) of those invited (34 control; 34 intervention); 64/68
      (94%; 95% CI 88.3% to 99.7%) provided 4-month follow-up data. Participants had a
      mean age of 49 years and mean PHQ-9 score of 16.8; 61% were female. Twenty-four
      of 34 (70.6%) adhered to the minimum treatment dose. The follow-up PHQ-9 (future
      primary outcome measure) pooled SD was 6.4 (95% CI 5.5 to 7.8); the magnitude of
      correlation between baseline and follow-up PHQ-9 scores was 0.42 (95% CI 0.19 to
      0.61). Of the participants, 66.7% and 30.0% recovered in the intervention and
      control groups, respectively; 66.7% and 13.3% responded to treatment in the
      intervention and control groups, respectively. CONCLUSIONS: A large-scale trial
      of Morita Therapy would require 133 participants per group and is feasible with
      minor modifications to the pilot trial protocol. Morita Therapy shows promise in
      treating depression and may provide patients with a distinct alternative to
      current treatments. TRIAL REGISTRATION NUMBER: ISRCTN17544090; Pre-results.

PMID- 30099393
TI  - Village-Integrated Eye Worker trial (VIEW): rationale and design of a cluster
      randomised trial to prevent corneal ulcers in resource-limited settings.
AB  - INTRODUCTION: Corneal opacity is a leading cause of blindness worldwide. In
      resource-limited settings, untreated traumatic corneal abrasions may result in
      infection and ultimately, opacity. Although antimicrobial treatment of corneal
      ulcers may successfully cure infections, the scarring that accompanies the
      resolution of infection can still result in visual impairment. Prevention may be
      the optimal approach for reducing corneal blindness. Studies have employed
      community health workers to provide prompt administration of antimicrobials after
      corneal abrasions to prevent infections, but these studies were not designed to
      determine the effectiveness of such a programme. METHODS AND ANALYSIS: The
      Village-Integrated Eye Worker trial (VIEW) is a cluster-randomised trial designed
      to assess the effectiveness of a community health worker intervention to prevent
      corneal ulcers. Twenty-four Village Development Committees (VDCs) in Nepal were
      randomised to receive a corneal ulcer prevention programme or to no intervention.
      Female Community Health Volunteers (FCHVs) in intervention VDCs are trained to
      diagnose corneal abrasions, provide antimicrobials and to refer participants when
      needed. An annual census is conducted over 3 years in all study VDCs to assess
      the incidence of corneal ulceration via corneal photography (primary outcome).
      Masked outcome assessors grade corneal photographs to determine the presence or
      absence of incident corneal opacities. The primary analysis is negative binomial
      regression to compare the incidence of corneal ulceration by study arm. ETHICS
      AND DISSEMINATION: The University of California San Francisco Committee on Human
      Research, Nepal Netra Jyoti Sangh and the Nepal Health Research Council have
      given ethical approval for the trial. The results of this trial will be presented
      at local and international meetings and submitted to peer-reviewed journals for
      publication. TRIAL REGISTRATION NUMBER: NCT01969786; Pre-results.

PMID- 30099396
TI  - Laparoscopic or open distal gastrectomy after neoadjuvant chemotherapy for
      advanced gastric cancer: study protocol for a randomised phase II trial.
AB  - INTRODUCTION: Current guidelines recommend open gastrectomy with D2 lymph node
      dissection and adjuvant chemotherapy as the standard treatment for advanced
      gastric cancer. However, the prognosis is not satisfactory. Perioperative
      chemotherapy has been proposed to improve survival. Although still in debate, the
      efficacy of laparoscopic distal gastrectomy (LDG) in patients with advanced
      gastric cancer has been demonstrated in a few trials. Therefore, LDG after
      neoadjuvant chemotherapy can be a candidate for future standard treatment on
      advanced distal gastric cancer. We propose a randomised phase II trial to compare
      LDG and open distal gastrectomy (ODG) after neoadjuvant chemotherapy for advanced
      gastric cancer. METHODS AND ANALYSIS: To test the efficacy and safety, a
      randomised, open-label, single-centre, phase II trial was designed to evaluate
      the non-inferiority of LDG compared with ODG after neoadjuvant chemotherapy, with
      3-year recurrence-free survival as the primary endpoint. The chosen critical
      value of a non-inferiority margin was an increase of <8%. The study started in
      2015 and enrolled 96 patients according to a prior sample size calculation.
      Intention-to-treat and per-protocol approach will be used for efficacy analysis,
      and as-treated analysis will be applied for safety analysis. The survival curves
      will be constructed as time-to-event plots using the Kaplan-Meier method and
      compared using log-rank tests and Cox proportional hazards model. All statistical
      analyses will be conducted in standard statistical software with a significance
      level of 0.05. ETHICS AND DISSEMINATION: This study was approved by the Peking
      University Cancer Hospital Ethics Committee. The results will be submitted for
      publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02404753;
      Pre-results.

PMID- 30099397
TI  - Efficacy and tolerance of early administration of tranexamic acid in patients
      with cirrhosis presenting with acute upper gastrointestinal bleeding: a study
      protocol for a multicentre, randomised, double-blind, placebo-controlled trial
      (the EXARHOSE study).
AB  - INTRODUCTION: The management of acute upper gastrointestinal bleeding (UGIB) is
      challenging in patients with cirrhosis, as it is responsible for severe
      complications and high mortality rates. Tranexamic acid (TXA) may help control
      the bleeding by counterbalancing cirrhosis-related hyperfibrinolysis. Still,
      there is a lack of unbiased data to conclude on its efficacy. The aim of this
      study is to evaluate the efficacy of TXA in the early treatment of acute UGIB in
      patients with cirrhosis. METHODS AND ANALYSIS: This study is a multicentre,
      randomised, double-blind, placebo-controlled trial, for adult patients with
      cirrhosis presenting with an acute UGIB and allocated to one of two arms: TXA or
      placebo (saline). Physicians from emergency mobile services, emergency
      departments (EDs) or intensive care units (ICUs) can include patients. Besides
      study intervention, standard care for UGIB will be performed as recommended.
      Intervention will consist an intravenous infusion of 10 mL of TXA (1 g) or
      saline, immediately followed by three identical intravenous infusions over 8
      hours each (total dose of 4 g of TXA or 40 mL of placebo over 24 hours). Main
      analyses will be conducted in intention to treat on every patient included, then
      in modified intention to treat on patients with underlying lesion of portal
      hypertension visualised by endoscopy. The main objective is to show efficacy of
      TXA until day 5 on a composite criterion (bleeding control, rebleeding episodes
      and mortality). Secondary objectives aim at showing the efficacy of TXA on each
      individual component of the main outcome measure and others at 6 weeks and later
      (transjugular intrahepatic portosystemic shunt procedure, cirrhosis-specific
      complications, length of stay in ICU and in hospital, safety and tolerance of
      TXA, liver transplantation). Included patients will be followed up to 1 year
      after inclusion.500 patients will be necessary to show a reduction in the
      prevalence of the primary outcome from 30% to 18% with a bilateral alpha risk of
      5% and a power of 80%. ETHICS AND DISSEMINATION: Ethical approval has been
      obtained from the Comite de Protection des Personnes Ile-de-France 1 (CPP-IDF1).
      Results will be disseminated via publications in peer-review medical journals and
      scientific forums. PROTOCOL VERSION: This protocol is based on the latest
      version, as established on 11 October 2017 and validated by the IRB CPP Ile-de
      France 1. TRIAL REGISTRATION NUMBER: NCT03023189.

PMID- 30099398
TI  - Effectiveness of traditional lectures and case methods in Swedish general
      practitioners' continuing medical education about COPD: a cluster randomised
      controlled trial.
AB  - OBJECTIVES: To study the effects of continuing medical education (CME) about
      chronic obstructive pulmonary disease (COPD) for general practitioners (GPs) by
      comparing two commonly used CME methods with each other and no CME (reference
      group). DESIGN: A pragmatic cluster randomised controlled trial with primary
      healthcare centres (PHCCs) as units of randomisation. SETTING, PARTICIPANTS AND
      INTERVENTIONS: 24 PHCCs in Stockholm County, Sweden, were randomised into two CME
      intervention arms: case method learning (CM) (n=12) and traditional lectures (TL)
      (n=12). A reference group without CME (n=11) was recruited separately. GPs
      (n=255) participated in the study arm to which their PHCC was allocated: CM,
      n=87; TL, n=93; and reference, n=75. Two 2-hour CME seminars were given in a
      period of 3 months. PRIMARY OUTCOME MEASURES: Changes in scores between baseline
      and 12 months on a 13-item questionnaire about evidence-based COPD management (0
      2 points/question, maximum total score 26 points). RESULTS: 133 (52%) GPs
      completed the questionnaire both at baseline and 12 months. Both CM and TL
      resulted in small yet significantly higher total scores at 12 months than at
      baseline (CM, 10.34 vs 11.44; TL, 10.21 vs 10.91; p<0.05); there were few
      significant differences between these CME methods. At both baseline and 12
      months, all three groups' scores were generally high on questions about smoking
      cessation support and low on those that measured spirometry interpretation
      skills, interprofessional care and management of multimorbidity. CONCLUSIONS:
      Neither short CM nor short TL CME sessions substantially improve GPs' skills in
      managing COPD. It is justified to challenge the use of these common CME methods
      as a strategy for improving GPs' level of knowledge about management of COPD and
      other complex chronic diseases characterised by multimorbidity. TRIAL
      REGISTRATION NUMBER: NCT02213809; Results.

PMID- 30099399
TI  - Cost-effectiveness of interventions for perinatal anxiety and/or depression: a
      systematic review.
AB  - OBJECTIVES: Anxiety and/or depression during pregnancy or year after childbirth
      is the most common complication of childbearing. Economic evaluations of
      interventions for the prevention or treatment of perinatal anxiety and/or
      depression (PAD) were systematically reviewed with the aim of guiding researchers
      and commissioners of perinatal mental health services towards potentially cost
      effective strategies. METHODS: Electronic searches were conducted on the MEDLINE,
      PsycINFO and NHS Economic Evaluation and Health Technology Assessment databases
      in September 2017 to identify relevant economic evaluations published since
      January 2000. Two stages of screening were used with prespecified
      inclusion/exclusion criteria. A data extraction form was designed prior to the
      literature search to capture key data. A published checklist was used to assess
      the quality of publications identified. RESULTS: Of the 168 non-duplicate
      citations identified, 8 studies met the inclusion criteria for the review; all
      but one focussing solely on postnatal depression in mothers. Interventions
      included prevention (3/8), treatment (3/8) or identification plus treatment
      (2/8). Two interventions were likely to be cost-effective, both incorporated
      identification plus treatment. Where the cost per quality-adjusted life year
      (QALY) gained was reported, interventions ranged from being dominant (cheaper and
      more effective than usual care) to costing L39 875/QALY. CONCLUSIONS: Uncertainty
      and heterogeneity across studies in terms of setting and design make it difficult
      to make direct comparisons or draw strong conclusions. However, the two
      interventions incorporating identification plus treatment of perinatal depression
      were both likely to be cost-effective. Many gaps were identified in the economic
      evidence, such as the cost-effectiveness of interventions for perinatal anxiety,
      antenatal depression or interventions for fathers. PROSPERO REGISTRATION NUMBER:
      CRD42016051133.

PMID- 30099400
TI  - Manual ventilation to prevent hypoxaemia during endotracheal intubation of
      critically ill adults: protocol and statistical analysis plan for a multicentre
      randomised trial.
AB  - INTRODUCTION: Hypoxaemia is the most common complication during endotracheal
      intubation of critically ill adults, and it increases the risk of cardiac arrest
      and death. Manual ventilation between induction and intubation has been
      hypothesised to decrease the incidence of hypoxaemia, but efficacy and safety
      data are lacking. METHODS AND ANALYSIS: The Preventing Hypoxemia with Manual
      Ventilation during Endotracheal Intubation trial is a prospective, multicentre,
      non-blinded randomised clinical trial being conducted in seven intensive care
      units in the USA. A total of 400 critically ill adults undergoing endotracheal
      intubation will be randomised 1:1 to receive prophylactic manual ventilation
      between induction and endotracheal intubation using a bag-valve-mask device or no
      prophylactic ventilation. The primary outcome is the lowest arterial oxygen
      saturation between induction and 2 min after successful endotracheal intubation,
      which will be analysed as an unadjusted, intention-to-treat comparison of
      patients randomised to prophylactic ventilation versus patients randomised to no
      prophylactic ventilation. The secondary outcome is the incidence of severe
      hypoxaemia, defined as any arterial oxygen saturation of less than 80% between
      induction and 2 min after endotracheal intubation. Enrolment began on 2 February
      2017 and is expected to be complete in May 2018. ETHICS AND DISSEMINATION: The
      trial was approved by the institutional review boards or designees of all
      participating centres. The results will be submitted for publication in a peer
      reviewed journal and presented at one or more scientific conferences. TRIAL
      REGISTRATION NUMBER: NCT03026322; Pre-results.

PMID- 30099401
TI  - Impact of maternity waiting homes on facility delivery among remote households in
      Zambia: protocol for a quasiexperimental, mixed-methods study.
AB  - INTRODUCTION: Maternity waiting homes (MWHs) aim to improve access to facility
      delivery in rural areas. However, there is limited rigorous evidence of their
      effectiveness. Using formative research, we developed an MWH intervention model
      with three components: infrastructure, management and linkage to services. This
      protocol describes a study to measure the impact of the MWH model on facility
      delivery among women living farthest (>=10 km) from their designated health
      facility in rural Zambia. This study will generate key new evidence to inform
      decision-making for MWH policy in Zambia and globally. METHODS AND ANALYSIS: We
      are conducting a mixed-methods quasiexperimental impact evaluation of the MWH
      model using a controlled before-and-after design in 40 health facility clusters.
      Clusters were assigned to the intervention or control group using two methods: 20
      clusters were randomly assigned using a matched-pair design; the other 20 were
      assigned without randomisation due to local political constraints. Overall, 20
      study clusters receive the MWH model intervention while 20 control clusters
      continue to implement the 'standard of care' for waiting mothers. We recruit a
      repeated cross section of 2400 randomly sampled recently delivered women at
      baseline (2016) and endline (2018); all participants are administered a household
      survey and a 10% subsample also participates in an in-depth interview. We will
      calculate descriptive statistics and adjusted ORs; qualitative data will be
      analysed using content analysis. The primary outcome is the probability of
      delivery at a health facility; secondary outcomes include utilisation of MWHs and
      maternal and neonatal health outcomes. ETHICS AND DISSEMINATION: Ethical
      approvals were obtained from the Boston University Institutional Review Board
      (IRB), University of Michigan IRB (deidentified data only) and the ERES Converge
      IRB in Zambia. Written informed consent is obtained prior to data collection.
      Results will be disseminated to key stakeholders in Zambia, then through open
      access journals, websites and international conferences. TRIAL REGISTRATION
      NUMBER: NCT02620436; Pre-results.

PMID- 30099403
TI  - Meanings of 'centredness' in long-term care facilities: a scoping review
      protocol.
AB  - INTRODUCTION: There is a growing demand for long-term care services for older
      adults that embrace a model of care centred on individual recipients of care. In
      long-term care, models of person, resident and relationship-centred care have
      been developed and implemented to promote independence, decision making and
      choices of residents. Although the concepts of centredness have been readily
      adopted in these environments, what constitutes centredness is often vague and
      lacks conceptual clarity and definition. The research questions guiding this
      scoping review are: (1) What are the defining attributes, conceptual boundaries
      and theoretical underpinnings of each centredness term in long-term care? (2) For
      what purposes have centredness directed models of care been used in this context?
      (3) What types of study designs have been used to examine centredness in this
      context? (4) What outcomes related to centredness have been reported or evaluated
      and how were they measured in long-term care? METHODS AND ANALYSIS: This review
      uses the methodological framework for conducting a scoping review by Arksey and
      O'Malley. The search strategy will be applied to nine bibliographic and citation
      databases, Google Scholar and the grey literature. Study selection will occur in
      a two-step process. First, the titles and abstracts of all search results will be
      screened by individual reviewers. Second, a full-text review will be conducted by
      a pair of reviewers. To be included articles must (1) define centredness in the
      context of long-term care; (2) describe the defining features of centredness; (3)
      explore the theoretical underpinnings of centredness; (4) outline outcomes of
      centredness or (5) use outcome measures related to centredness. Data will be
      extracted from included studies and analysed using thematic analysis as described
      by Braun and Clark. ETHICS AND DISSEMINATION: Research ethics approval is not
      required for this scoping review. Dissemination strategies will follow a targeted
      and tailored approach based on study findings.

PMID- 30099402
TI  - Pain education for patients with non-specific low back pain in Nepal: protocol of
      a feasibility randomised clinical trial (PEN-LBP Trial).
AB  - INTRODUCTION: Low back pain (LBP) is the leading cause of years lived with
      disability in Nepal and elsewhere. Management of LBP that is evidence-based,
      easily accessible, cost-effective and culturally appropriate is desirable. The
      primary aim of this feasibility study is to determine if it is feasible to
      conduct a full randomised clinical trial evaluating the effectiveness of pain
      education as an intervention for individuals with LBP in Nepal, relative to
      guideline-based physiotherapy treatment. The findings of the study will inform
      the planning of a full clinical trial and if any modifications are required to
      the protocol before undertaking a full trial. METHODS/ANALYSIS: This protocol
      describes an assessor-blinded feasibility clinical trial investigating
      feasibility of the pain education intervention in patients with non-specific LBP
      in a physiotherapy hospital in Kathmandu, Nepal. Forty patients with LBP will be
      randomly allocated to either pain education or guideline-based physiotherapy
      treatment (control). Outcomes will be assessed at baseline and at a 1 week post
      treatment. The primary outcomes are related to feasibility, including: (1)
      participant willingness to participate in a randomised clinical trial, (2)
      feasibility of assessor blinding, (3) eligibility and recruitment rates, (4)
      acceptability of screening procedures and random allocation, (5) possible
      contamination between the groups, (6) intervention credibility, (7) intervention
      adherence, (8) treatment satisfaction and (9) difficulty in understanding the
      interventions being provided. ETHICS/DISSEMINATION: The protocol was approved by
      Nepal Health Research Council (NHRC; registration number: 422/2017) and
      University of Otago Human Ethics Committee for Health (registration number:
      H17/157). The results of the study will be presented at national and
      international conferences and published in a peer-reviewed journal. TRIAL
      REGISTRATION NUMBER: NCT03387228; Pre-results.

PMID- 30099404
TI  - Protocol paper for the 'Harnessing resources from the internet to maximise
      outcomes from GP consultations (HaRI)' study: a mixed qualitative methods study.
AB  - INTRODUCTION: Many patients now turn to the internet as a resource for healthcare
      information and advice. However, patients' use of the internet to manage their
      health has been positioned as a potential source of strain on the doctor-patient
      relationship in primary care. The current evidence about what happens when
      internet-derived health information is introduced during consultations has relied
      on qualitative data derived from interview or questionnaire studies. The
      'Harnessing resources from the internet to maximise outcomes from GP
      consultations (HaRI)' study combines questionnaire, interview and video-recorded
      consultation data to address this issue more fully. METHODS AND ANALYSIS: Three
      data collection methods are employed: preconsultation patient questionnaires,
      video-recorded consultations between general practitioners (GP) and patients, and
      semistructured interviews with GPs and patients. We seek to recruit 10 GPs
      practising in Southeast England. We aim to collect up to 30 patient
      questionnaires and video-recorded consultations per GP, yielding up to 300. Up to
      30 patients (approximately three per participating GP) will be selected for
      interviews sampled for a wide range of sociodemographic characteristics, and a
      variety of ways the use of, or information from, the internet was present or
      absent during their consultation. We will interview all 10 participating GPs
      about their views of online health information, reflecting on their own usage of
      online information during consultations and their patients' references to online
      health information. Descriptive, conversation and thematic analysis will be used
      respectively for the patient questionnaires, video-recorded consultations and
      interviews. ETHICS AND DISSEMINATION: Ethical approval has been granted by the
      London-Camden & Kings Cross Research Ethics Committee. Alongside journal
      publications, dissemination activities include the creation of a toolkit to be
      shared with patients and doctors, to guide discussions of material from the
      internet in consultations.

PMID- 30099406
TI  - Correction: A pushing chronic care forward in Abu Dhabi by identifying priorities
      and addressing barriers: a modified Delphi technique.

PMID- 30099405
TI  - Increasing engagement in advance care planning using a behaviour change model:
      study protocol for the STAMP randomised controlled trials.
AB  - INTRODUCTION: Advance care planning (ACP) is a key component of high-quality end
      of-life care but is underused. Interventions based on models of behaviour change
      may fill an important gap in available programmes to increase ACP engagement.
      Such interventions are designed for broad outreach and flexibility in delivery.
      The purpose of the Sharing and Talking about My Preferences study is to examine
      the efficacy of three behaviour change approaches to increasing ACP engagement
      through two related randomised controlled trials being conducted in different
      settings (Veterans Affairs (VA) medical centre and community). METHODS AND
      ANALYSIS: Eligible participants are 55 years or older. Participants in the
      community are being recruited in person in primary care and specialty outpatient
      practices and senior living sites, and participants in the VA are recruited by
      telephone. In the community, randomisation is at the level of the practice or
      site, with all persons at a given practice/site receiving either computer
      tailored feedback with a behaviour stage-matched brochure (computer-tailored
      intervention (CTI)) or usual care. At the VA, randomisation is at the level of
      the participant and is stratified by the number of ACP behaviours completed at
      baseline. Participants are randomised to one of four groups: CTI, motivational
      interviewing, motivational enhancement therapy or usual care. The primary outcome
      is completion of four key ACP behaviours: identification of a surrogate decision
      maker, communication about goals, completing advance directives and ensuring
      documents are in the medical record. Analysis will be conducted using mixed
      effects models, taking into account the clustered randomisation for the community
      study. ETHICS AND RANDOMISATION: The studies have been approved by the
      appropriate Institutional Review Boards and are being overseen by a Safety
      Monitoring Committee. The results of these studies will be disseminated to
      academic audiences and leadership in in the community and VA sites. TRIAL
      REGISTRATION NUMBERS: NCT03137459 and NCT03103828.

PMID- 30099407
TI  - CD147 expression is associated with poor overall survival in chemotherapy treated
      triple-negative breast cancer.
AB  - AIMS: In breast cancer models, the functional roles of CD147 in proliferation,
      invasion and treatment resistance have been widely reported. However, there are
      only a few studies examining the clinicopathological correlation and prognostic
      relevance of CD147 in breast cancer, especially in relation to breast cancer
      molecular subtypes. METHODS: In this study, we analysed CD147 expression in a
      large cohort of breast cancers, correlating with clinicopathological features and
      the expression of a comprehensive panel of biomarkers in triple-negative breast
      cancer (TNBC) and non-TNBC subsets. Its relationship with patients' survival was
      also analysed. RESULTS: CD147 was expressed in 11.9%(140/1174) of all cases and
      in 23.8% (40/168) of TNBC. The expression was associated with tumour histological
      subtypes (p=0.01) and most commonly seen in carcinoma with medullary features
      (26.0%). CD147 expression correlated with high tumour grade, presence of necrosis
      and basal-like breast cancer (BLBC) subtype, high Ki67 and expression of some
      other basal markers and stem-like markers. CD147 expression was also associated
      with poor overall survival in chemotherapy treated patients with TNBC.
      CONCLUSIONS: CD147 is a putative marker in identifying TNBC or BLBC, and may be
      useful as a prognosis indicator for patients with TNBC or BLBC post chemotherapy.

PMID- 30099409
TI  - Observing an analyzer's operational life cycle: a useful management tool for
      clinical laboratories.

PMID- 30099408
TI  - Bird-biting mosquitoes on farms in southern England.

PMID- 30099410
TI  - Local inhibition of carbonic anhydrase does not decrease sweat rate.
AB  - BACKGROUND: The purpose of this study was to measure sweat rate during exercise
      in the heat after directly inhibiting carbonic anhydrase (CA) in eccrine sweat
      glands via transdermal iontophoresis of acetazolamide. It was hypothesized that
      if CA was important for sweat production, local administration of acetazolamide,
      without the confounding systemic effects of dehydration typically associated with
      past studies, would have a significant effect on sweat rate during exercise.
      METHODS: Ten healthy subjects volunteered to exercise in the heat following
      acetazolamide or distilled water iontophoresis on the forearm. RESULTS: The
      distilled water iontophoresis site had a mean sweat rate during exercise in the
      heat of 0.59+/-0.31 MUL/cm2/min, while the acetazolamide iontophoresis site had a
      mean sweat rate of 0.63+/-0.36 MUL/cm2/min (p>0.05). CONCLUSIONS: The most
      important finding of the current study was that iontophoresis of acetazolamide
      did not significantly decrease sweat rate during exercise in the heat. Such
      results suggest that in past studies it was systemic dehydration, and not CA
      inhibition at the level of the sweat gland, that caused the reported decreased
      sweat rate.

PMID- 30099411
TI  - Effect of caffeine on alcohol consumption and alcohol-induced conditioned place
      preference in rodents.
AB  - Background The aim of the study was to determine the effect of caffeine on
      alcohol consumption with or without deprivation and alcohol-induced conditioned
      place preference. Methods In the present study, we examined the effects of
      caffeine (2.5, 5 and 10 mg/kg) on alcohol consumption in Wistar rats with or
      without periods of deprivation in an unlimited-access, two-bottle, free choice
      drinking procedure after a stable baseline alcohol consumption was established.
      Conditioned place preference (CPP) was established by intraperitoneal injections
      of alcohol (2 g/kg) in a 12-day conditioning schedule in mice. The effect of
      caffeine (3 mg/kg) on CPP expression was determined by a final post-conditioning
      test following 12 conditioning sessions with alcohol. The effect of caffeine (3
      mg/kg) on the reinstatement of alcohol-induced CPP was determined in a final post
      conditioning test following 12 conditioning sessions with alcohol and the
      extinction of alcohol-induced CPP. Results Alcohol deprivation for 3 days did not
      result in alcohol deprivation effect (ADE). While caffeine (10 mg/kg) caused a
      significant (p<0.05) reduction in alcohol consumption compared with the baseline
      following a period of alcohol deprivation, it did not cause a change in alcohol
      consumption compared with the baseline in the study without alcohol deprivation
      phase. Caffeine significantly (p<0.05) reduced the expression of alcohol-induced
      CPP compared to saline and blocked the reinstatement of alcohol-induced CPP
      following the injection of a priming dose (0.4 g/kg) of alcohol. Conclusions
      Given that caffeine is an adenosine receptor antagonist, our findings suggest a
      role for adenosine receptors in the alcohol reward and alcohol-seeking behaviour.

PMID- 30099412
TI  - Asymmetric dimethylarginine and soluble inter-cellular adhesion molecule-1 serum
      levels alteration following ginger supplementation in patients with type 2
      diabetes: a randomized double-blind, placebo-controlled clinical trial.
AB  - Aims Patients with type 2 diabetes mellitus (T2DM) are prone to cardiovascular
      disease (CVD) due to inflammation process and oxidative stress. ADMA (Asymmetric
      dimethylarginine) and ICAM-1 (inter-cellular adhesion molecule-1) play an
      important role in CVD pathogenesis. Ginger as an anti-oxidant and anti
      inflammation can effect on these biomarkers. The aim of present study was to
      characterize the effect of ginger supplementation on ADMA and ICAM-1 serum levels
      in patients with T2DM. Methods The present study is a randomized double-blind
      clinical trial which is conducted among 45 diabetic patients (nginger=23,
      nplacebo=22). The participants were randomly divided into two intervention and
      placebo groups which were received 2 g ginger powder and 2 g wheat flour for 10
      weeks, respectively. ADMA and ICAM-1 concentration were measured by ELISA method.
      Results Ginger supplementation decreased ADMA serum levels significantly
      (P=0.002) and sICAM-1 serum levels marginally (P=0.097) in supplementation group
      after intervention. No significant difference was observed between placebo and
      supplementation groups. Conclusions Present study was conducted among patients
      with type 2 diabetes mellitus to investigate the effect of ginger supplementation
      on ADMA and sICAM-1 levels. There was a significant decrement in ADMA serum
      concentration and slight reduction in sICAM-1 levels in intervention group. The
      amount of reduction in both biomarkers was not statistically significant in
      between-groups comparison.

PMID- 30099413
TI  - Modulatory effect of some citrus (Citrus limon, Citrus reticulata, Citrus maxima)
      peels on monoamine oxidase, phosphodiesterase-5 and angiotensin-1 converting
      enzyme activities in rat heart homogenate.
AB  - Background Citrus peels have been reported useful in folk medicine for the
      management of cardiovascular diseases, but there is dearth of information on the
      possible mechanisms for their therapeutic action. The aim of this study was to
      investigate the effect of methanolic extracts from some citrus [lime (Citrus
      limon), tangerine (Citrus reticulata), shaddock (Citrus maxima)] peels on some
      enzymes relevant to the management of cardiovascular diseases [monoamine oxidase
      (MAO), phosphodiesterase-5 (PDE-5) and angiotensin-1-converting enzyme (ACE)].
      Methods Effect of methanolic extracts of lime, tangerine and shaddock peels on
      MAO, PDE-5 and ACE were carried out using standard methods. In addition, the
      ability of the extracts to prevent oxidative damage in rat heart homogenates was
      also investigated. Finally, the total polyphenol content of extracts was
      determined. Results The results revealed that methanolic extracts of lime,
      tangerine and shaddock peels inhibited MAO, PDE-5, ACE and pro-oxidants induced
      lipid peroxidation in rat heart homogenate in a concentration-dependent manner.
      Conclusions Findings in this study revealed citrus peel methanolic extracts as
      natural inhibitor of enzymes (MAO, PDE-5 and ACE) implicated in cardiovascular
      diseases. Therefore, citrus peels could help in the management of cardiovascular
      diseases possibly through inhibition of these enzymes.

PMID- 30099414
TI  - Pathogenesis of insulin resistance in pregnant women with obesity.
AB  - OBJECTIVE: Introduction: Obesity is one of the most important medical and social
      problems in many countries of the world, as it is associated with the development
      of the most common non-communicable diseases: cardiovascular, type II diabetes
      mellitus, motor disorders, non-alcoholic fatty liver disease (NHAHP) and others.
      The aim of this paper is to analyze the pathogenetic mechanisms of insulin
      resistance development in pregnant women with varying obesity degrees in early
      and late gestation periods. PATIENTS AND METHODS: Materials and methods: 459
      pregnant women were examined at the Poltava City Clinical Maternity Hospital in
      the early (9-13 weeks) and late gestation periods (34-38 weeks). Metabolic
      disorders in pregnant women were studied by carbohydrate and lipid metabolism
      indices. RESULTS: Results: Due to increased insulin resistance and reduced
      glucose absorption by tissues of pregnant women with obesity, there are
      prerequisites for the development of energy insufficiency. Obese women pregnancy
      runs on the background of hypertriglyceridemia and type IV hyperlipoproteinemia.
      The general pathogenic consequence of the insulin resistance progression during
      pregnancy in obese women is an energy deficiency increase, which causes a
      threatening obstetric and perinatal complications frequency increase. CONCLUSION:
      Conclusions: The progression of insulin resistance during pregnancy of women with
      varying degrees of obesity is the pathogenetic basis of energy insufficiency and
      the reduction of adaptive mechanisms of pregnant women with obesity, as evidenced
      by the increase in obstetric and perinatal complications frequency.

PMID- 30099415
TI  - Correlation of electrophysiological parameters of peripheral nerves and manual
      dexterity in patients with amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Introduction: Amyotrophic lateral sclerosis (ALS) is a
      neurodegenerative disease affecting upper and lower motor neurons, presenting
      with various manifestations, leading to progressing disability, with poor
      prognosis, and with no options for successful treatment. In its classic form the
      central and peripheral motor neurons are simultaneously affected at the
      beginning; the bulbar-onset ALS successively involving other parts of the nervous
      system is slightly less common. The aim: To demonstrate a correlation between
      electrophysiological parameters of peripheral nerves and loss of manual dexterity
      in the ALS. PATIENTS AND METHODS: Materials and methods: The analysis covered
      results of electrophysiological tests of motor conductivity in median and ulnar
      nerves, and results of the Mira Stambak and Rene Zazzo tests normally used to
      evaluate lateralisation, while in this study they were adapted to verify manual
      dexterity. The study covered 20 patients with clinically confirmed or possible
      ALS determined on the basis of the EI Escorial criteria. Half (10 people) of the
      studied group had limb-onset ALS, while the other half had the bulbar-onset ALS.
      RESULTS: Results: When evaluating a correlation between the results of
      electrophysiological tests and the results of the Mira Stambak and Rene Zazzo
      tests, a significant relationship was found between a reduction in an amplitude
      of the compound muscle action potential (CMAP) and deterioration in manual
      dexterity in the subjects, with a tendency for progression in these deviations,
      but with their interdependency maintained. CONCLUSION: Conclusions: 1. A loss of
      motor cells in the anterior horns of the spinal cord is reflected in the
      deterioration of manual dexterity in ALS patients. 2. A significant correlation
      is found between a loss in manual dexterity and an increase in changes in motor
      conductivity.

PMID- 30099416
TI  - [The analysis of association between ENPP1 K121Q polymorphism and risk factors of
      type 2 diabetes mellitus in ukrainian population].
AB  - OBJECTIVE: Introduction: More than 100 genes have been described associations
      between single nucleotide polymorphisms and type 2 diabetes mellitus (T2DM).
      Among these candidate genes, Ectonucleotide Pyrophosphatase/Phosphodiesterase 1
      (ENPP1), is located on the long arm of chromosome 6 (6q23.2) and encodes for a
      protein which is one of the factors determining the insulin sensitivity. An
      allelic polymorphism in exon 4 of ENPP1 (rs1044498) has been designated K121Q and
      widely investigated in T2DM in different populations. The aim: To analyze the
      association between ENPP1 K121Q polymorphism with the risk factors of type 2
      diabetes mellitus in the Ukrainian population. PATIENTS AND METHODS: Materials
      and methods: Venous blood of 317 patients with type 2 diabetes mellitus and 302
      controls was used for analysis. ENPP1 K121Q genotyping was performed using PCR
      RFLP method. RESULTS: Results: Our results revealed that ratio of K/K
      homozygotes, K/Q heterozygotes and Q/Q homozygotes between case and control
      groups was significantly different (59.3%, 34.1%, 6.6% vs 67.9%, 28.5%, 3.6%, P =
      0.05). Method of binary logistic regression shown that a reliable relationship
      was established in the general group for KQ/QQ vs K/K genetic model (P = 0.027).
      It was shown that in carriers of the minor Q-allele, the risk of T2DM is 1.4x
      higher than in homozygotes in the main K-allele (95% CI = 1.043-2.016). After
      adjusting for age, sex, smoking habit, BMI, obesity and the presence of
      hypertension, the reliability of these results persisted (P = 0.026). CONCLUSION:
      Conclusions: ENPP1 K121Q polymorphism is associated with T2DM in Ukrainian
      population. In carriers of the minor Q-allele the risk of T2DM is 1.4x higher
      than in homozygotes in the main K-allele. The risk increases in patients with BMI
      >= 25 kg/m2.

PMID- 30099417
TI  - Prevention of ventilator-associated pneumonia in newborns.
AB  - OBJECTIVE: The aim of the study is to optimize the prevention of the development
      of ventilator-associated pneumonia in newborns by developing a method for
      tracheal rehabilitation and assessment of its effectiveness. PATIENTS AND
      METHODS: Materials and methods: A prospective cohort randomized clinical study
      was organized, particularly artificial ventilation of the lungs was conducted on
      90 newborns. Patients were divided into two groups. In the main group (n = 50) an
      intubation tube of author's design was used, which design allowed prophylactic
      tracheal sanation on the outer wall of the intubation tube, which included vacuum
      aspiration of the tracheal secretion and irrigation with a solution of antiseptic
      decamethoxin 0.02% every 3 hours. In the comparative group (n = 40) the classical
      non-cuff structure of the intubation tube was used; preventive tracheal sanation
      on the outer wall of the intubation tube was not carried out. RESULTS: Results
      and conclusions: Preventive tracheal sanation on the outer surface of the
      intubation tube in newborns units that undergo artificial ventilation of the
      lungs exhibit high efficiency against the main types of microorganisms that are
      dangerous from the point of view of the development of ventilator-associated
      pneumonia. The use of prophylactic tracheal sanitization in newborns - patients
      of neonatal intensive care units, which undergoes artificial ventilation of the
      lungs, can significantly lower the frequency of the implementation of ventilator
      associated pneumonia.

PMID- 30099418
TI  - The hypo- and hyperelementosis to women of the Republic of Sakha (Yakutia).
AB  - OBJECTIVE: Introduction: Stability of the chemical composition of the body is one
      of the most important and mandatory conditions for its normal functioning.
      Accordingly, deviations in the content of chemical elements caused by
      environmental, climatic-geographical factors or diseases will lead to a wide
      range of disorders in the state of health. Therefore, the identification and
      evaluation of deviations in the exchange of macro- and microelements, as well as
      their correction, are a promising direction of modern medicine. The aim of the
      work is to reveal the regularity of distribution of diselementoses and the
      elemental profile of pathology in women from various regions of the Republic of
      Sakha (Yakutia). PATIENTS AND METHODS: Materials and methods: Using the
      multielement analysis system using AES-ISP and MS-ISP methods, the content of
      chemical elements in the hair of 555 women from various regions of the Republic
      of Sakha (Yakutia) was investigated. The study of hair was conducted on the
      content of 24 chemical elements (Al, As, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na,
      Ni, P, Pb, Se, Si, Sn, Ti, V, Zn , MUg / g). RESULTS: Results and conclusions:
      The results obtained show that the risk of hyperelementosis in the female
      population of the Republic of Sakha (Yakutia) is significantly increasing in the
      direction of south-south; in the direction of north-south the risk of development
      of hypo-elemental diseases increases significantly. At the same time, the central
      regions of the republic are an exception to the general scheme: the prevalence of
      excessive accumulation in the hair as toxic and essential chemical elements is
      also great here, as in the arctic regions of the republic.

PMID- 30099419
TI  - [The influence of type 2 diabetes mellitus on early and late results of
      percutaneous coronary intervention for non-st segment elevation myocardial
      infarction].
AB  - OBJECTIVE: The aim: We aimed at assessing the prognostic significance of diabetes
      mellitus in patients with NSTEMI treated with PCI as well as determining the
      independent predictors of worse prognosis. PATIENTS AND METHODS: Materials and
      methods: We performed a retrospective analysis of 830 patients hospitalized
      between January 2006 and December 2012 with diagnoses of NSTEMI and undergoing
      angiography and percutaneous coronary interventions. Patients were divided into
      two groups: with diabetes mellitus (246 patients) and without diabetes mellitus
      (584 patients). All patients were followed up at 30 days, 12 months, and 24
      months. RESULTS: Results: Diabetes mellitus was an independent risk factor for
      the occurrence of complex endpoints (HR, 1.64) at the 24-month follow-up visit:
      myocardial infarction not ending with death analyzed alone (HR, 1.82), death
      analyzed together with myocardial infarction not ending with death (HR, 1.65),
      and repeated revascularization performed due to the presence of ischemia (HR,
      1.63) Moreover, diabetes mellitus was one of the factors influencing 24-month
      mortality, but its independent influence was at the threshold of significance
      (HR, 1.46; p=0.08). In the multiple factor analysis the independent risk factors
      for death at the 24-month follow-up were: creatinine concentration on admission,
      LVEF, age, and cardiogenic shock during hospitalization. CONCLUSION: Conclusions:
      Despite similar efficacy of percutaneous coronary intervention, diabetes mellitus
      was associated with a worse in-hospital and long-term outcomes. Diabetes mellitus
      did not affect long-term mortality.

PMID- 30099420
TI  - Problems of nitrate water pollution in poltava region.
AB  - OBJECTIVE: Introduction: The topicality is determined bypriority and importance
      of researches that have preventive referral directed on provision of harmonious
      growth and early childhood development, children's resistance to the infection's
      effects and other unfavorable external factors. There are problems about the role
      of permanent nitrate load in the formation of children health issues, especially
      children who live in the area with high nitrate levels in drinking well water.
      The aim is to evaluate the physical development of children who live in nitrate
      contaminated areas. PATIENTS AND METHODS: Materials and methods: Object of study 
      children living in nitrate-polluted locality. Subject of study - violation of
      physical development and morbidity of children in interrelation of factors that
      determined. Methods - clinical, biochemical, instrumental, sanitary-hygienic,
      statistical. RESULTS: Results: When studying the content of methemoglobin among
      adult population in village areas, where well water with a high concentration of
      nitrates is consumed and in the city where centralized water supply is used, it
      was observed that rural people have a higher level of methemoglobin. Parents who
      lived in nitrates-polluted territories have a chronic pathology formed in
      childhood that affects the morbidity of their children, which affects the health
      of the nation. CONCLUSION: Conclusions: centralized water supply was conducted
      many locations over the years, but parents who lived in nitrates-polluted
      territories have a chronic pathology formed in childhood that affects the
      morbidity of their children.

PMID- 30099421
TI  - Current tendencies in the nutrition of women and pregnant women of industrial
      region of ukraine and their influence on microelements supply.
AB  - OBJECTIVE: Introduction: During recent decades there has been observed a
      violation in the structure of nutrition of the population with a significant
      decrease in the consumption of biologically valuable products, resulting in the
      development of the so-called "latent hunger", particularly in sensitive groups of
      population - women of reproductive age and pregnant women. The aim: To study
      nutritional peculiarities and the level of biotic and abiotic trace elements
      intake into the body of the female population, residents of the industrial
      region. PATIENTS AND METHODS: Materials and methods: Physiological and hygienic
      nutritional assessment was carried out in 185 women and pregnant women, residents
      of industrial and non-industrial cities of Dnipropetrovsk region of Ukraine.
      Actual nutrition was studied using the 24-hour food reproduction method
      recommended by the WHO. Calculation of the content of trace elements in the diet
      was carried out using well-known techniques, followed by the assessment of their
      compliance by the level of permissible daily load for toxic trace elements - lead
      and cadmium and daily requirements - for essential elements, zinc and copper.
      RESULTS: Results: Studies performed have found significant violations of the
      requirements of rational nutrition in relation to its regime and the average
      daily food package, which is excessive in consumption of bread and bakery
      products, sugar and confectionery products by 9,9%-67,6% and is characterized by
      a shortage of other groups of foodstuff with various degree of evidence. On the
      background of deformation of nutrition there is observed an increased income of
      xenobiotics - lead and cadmium into the female body, which is by 3,8-7,8 times
      higher than the level of so-called "optimal one". At the same time the level of
      income of essential micronutrients - zinc and copper was by 9,5-45,7% lower than
      the RDI. CONCLUSION: Conclusions: Nutrition of fertile age and pregnant women,
      residents of industrial regions of Ukraine, does not meet the requirements of
      rational nutrition due to violations in diet, in quantitative and qualitative
      nutritional budget, excessive intake of xenobiotics and deficiency of essential
      micronutrients.

PMID- 30099423
TI  - [Clinical and laboratory grounding of using medication based on the antiseptic
      troklosene to treat patients with chronic generalized periodontitis of the ii and
      iii degrees of severity].
AB  - OBJECTIVE: Introduction: Periodontal diseases take second place in the world
      among dental diseases and tend to be ubiquitous regardless of age, sex and place
      of residence. According to the modern point of view inflammatory periodontal
      diseases refer to infectious chronic inflammatory diseases, therefore, the
      normalization of the microflora of the oral cavity is an essential condition for
      their rational therapy. The aim: To increase the effectiveness of conservative
      treatment of chronic generalized periodontitis of the II-nd and III-rd severity
      using the medication based on the antiseptic Troklosene. PATIENTS AND METHODS:
      Materials and methods: 34 patients of age 45 to 55 years who were diagnosed with
      chronic generalized periodontitis of the IIInd and IIIrd degree of severity were
      examined and treated. All patients reported signs of the disease for 3-15 years.
      Patients of the study group by simple randomization were divided into two
      subgroups, depending on the therapeutic treatment performed. The I-st subgroup 
      16 patients treated with the additional use of the medication based on the
      antiseptic Troklosene, the IInd subgroup - 18 patients who were treated without
      using this drug. RESULTS: Results: Analyzing the results after the treatment in
      the patients of the I -st and II -nd subgroup, they noted a decrease in PMA
      index, Green-Vermillion index, bleeding index. Pathological mobility of teeth
      decreased to the I degree. The hygienic condition of the oral cavity was
      characterized in patients of both subgroups after treatment as satisfactory. In
      patients of the Ist subgroup (with the additional use of the medication based on
      the antiseptic Troklosene), after the 5th visit there were signs of remission,
      and in the IInd subgroup (using standard base therapy), after 7 visits, there
      were signs of clinical remission. With the additional use of the drug based on
      the antiseptic Troklosene, in contrast to the traditional therapy, a change in
      the bacterial ratio of microorganisms occurred, which influenced a significant
      decrease in the total bacterial mass. CONCLUSION: Conclusion: The best results
      were obtained in the Ist subgroup, where along with the standard base therapy,
      the supplement of based on the antiseptic Troklosene was used additionally.
      Introduction to the treatment regimen for patients with chronic generalized
      periodontitis with II and III severity of the drug based on the antiseptic
      Troklosene contributed to a stable clinical effect, as evidenced by the dynamics
      of clinical indicators and the reduction in the number of visits. Also, a change
      in the bacterial ratio of microorganisms with a significant decrease due to
      Enterobacterium spp. is noted. To maintain this result, it is recommended to
      continue the use of the drug based on the antiseptic Troklosene with a frequency
      of 4 times per day within 7 days after the end of treatment.

PMID- 30099422
TI  - ASIT as the component of bronchial asthma's therapy can improve the adherence to
      the treatment.
AB  - OBJECTIVE: The aim: To compare the treatment adherence of patients with Bronchial
      Asthma (BA) receiving basic treatment and its combination with allergen-specific
      immunotherapy. PATIENTS AND METHODS: Materials and methods: The study included
      104 patients aged from 18 to 50 with BA. All patients were divided into two
      groups. The main group (MG) consisted of 51 patients receiving basic medical
      treatment and ASIT. 38 of them received subcutaneous ASIT and 13 patients
      received sublingual ASIT. The comparative group (CG) consisted of 53 patients who
      received only basic therapy. The patients' observation duration was for a year.
      RESULTS: Results: All patients were done the computer spirometry with a
      bronchodilation test, determination of the total IgE level, questionnaires
      (quality of life, control of asthma, adherence to treatment). Also the major and
      minor component of allergy house dust mites and specific IgG4 were determined in
      patients of main groups. After 12 months of observation in both groups the
      spirometry rates improved (the main group result was 16.9%, the control group -
      was 12.8%). The indicators of asthma's control also increased (MG by 28%, in CG -
      21%, (p <0,05)). After individual conversations and training the patients
      improved and adherence to the treatment too. In the beginning of our research the
      mean level in MG was 3.2 +/- 0.3 points, in - CG-3.3 +/- 0.2 points (p> 0.05),
      after 12 months it increased to 6.3 +/- 0.2 points in MG vs 5. 8 +/- 0.1 points
      in CG (p <0.05). CONCLUSION: Conclusion: Patients' combining basic therapy with
      SIT had significantly better results of the overall BA's controllability compared
      to the patients' receiving only basic therapy.

PMID- 30099424
TI  - DYNAMICS OF CONTENT OF SOME MINERALS IN TEENAGERS WITH CARDIOVASCULAR SYSTEM
      PATHOLOGY AGAINST THE BACKGROUND OF CHRONIC TONSILLITIS ZMIANY ZAWARTOSCI
      NIEKTORYCH SKLADNIKOW MINERALNYCH U MLODZIEZY Z CHOROBAMI UKLADU SERCOWO
      NACZYNIOWEGO JAKO PODLOZE ROZWOJU PRZEWLEKLEGO ZAPALENIA MIGDALKOW
      PODNIEBIENNYCH.
AB  - OBJECTIVE: Introduction: Chronic diseases of the upper respiratory tract in
      children and teenagers, such as chronic tonsillitis is quite common in pediatric
      populations, accompanied by changes in reactivity, causing a risk of
      complications. Due to the fact that the child's body resistance to acute
      infectious diseases depends on the sufficiency of trace elements, then at present
      stage greatly increased interest in deeper study of exchange of macro- and
      microelements in the human body in normal and pathological conditions. The aim:
      To study the dynamics of zinc, iron, potassium and magnesium in adolescents with
      disorders of the cardiovascular system with chronic tonsillitis. PATIENTS AND
      METHODS: Materials and methods: It was examined 63 patients with chronic
      tonsillitis, among them- 31 children suffer from chronic tonsillitis off-damage
      to the cardiovascular system (I group), 32 patients with disorders of the
      cardiovascular system against the background of chronic tonsillitis (II group).
      The content of trace elements zinc, iron, minerals potassium and magnesium was
      analyzed. The measurement and calculation were done according to AAS-SPECTR
      program. Analysis and statistics treatment was done on using application programs
      STATISTICA 7.0 and MS Excel XP. RESULTS: Results: In result of investigation it
      was found a violation of trace element composition in the blood serum. Thus, in
      patients with chronic tonsillitis without cardiovascular system damage during
      hospitalization was observed a significant decrease in the concentration of iron
      to (15,47 +/- 1,12) mmol/l. Similar changes were observed with the concentration
      of zinc in the blood serum. In patients with chronic tonsillitis without
      cardiovascular system damage during hospitalization was observed a significant
      decrease in the concentration of iron to (15,47 +/- 1,12) mmol/l. Similar changes
      were observed with the concentration of zinc in the blood serum of patients of I
      groups during hospitalization (10,89 +/- 0,57mmol/l) and was significantly lower
      compared with the data of healthy children (18,40 +/- 0,71 mmol/l (p <0.05)).
      CONCLUSION: Sonclusions: It should be noted that children with tonsillogene
      cardiac lesions during hospitalization have a significant decreasing in the level
      of magnesium compared with indicators of children without pathology of the
      cardiovascular system. After treatment, the normalization of trace elements iron,
      zinc, magnesium did not happen, moreover, significant changes were observed in
      patients with heart disease against the background of chronic tonsillitis.

PMID- 30099425
TI  - [Prevalence of acute symptomatic seizure after intracerebral hemorrhage].
AB  - OBJECTIVE: Introdustion: Acute symptomatic seizure (ASS) is a most frequently
      complication after a stroke. Seizures could be associated with the worse outcome.
      Nowadays the prophylactic antiepileptic treatment after the stroke is not
      advisable. However this question have to be discussed in a particular groups of
      patients. The aim: To study the prevalence of ASS in the particular groups of
      patients after intracerebral hemorrhage as well as to determine the predictors of
      the sizure occurrence in these groups of patients. PATIENTS AND METHODS:
      Materials and methods: The retrospective analysis of the clinical features of
      intracerebral hemorrhage for 305 patients was performed. Among them there were
      127 patients with aneurysmal subarachnoid hemorrhage as well as 178 patients were
      with nonaneurysmal intracerebral hemorrhage. RESULTS: Results: In 12 patients
      from 127 with subarachnoid hemorrhage were occurred onset seizures. 4 patients
      from 12 with subarachnoid hemorrhage died (28.5% of all deaths in the group of
      patients with subarachnoid hemorrhage (SAH)). In the group of patients with
      seizures 10 of them had aneurysm in anterior part of Willi's Circle. In 11
      patients from 178 with nonaneurysmal intracerebral hemorrhage occurred onset
      seizures. Only one patient from 72 with medial localization of intracerebral
      hemorrhage had seizures. CONCLUSION: Conclusions: Prevalence of ASS after
      intracerebral hemorrhage reaches 7.5%, in the group of patients with SAH - 9.5%,
      in the group of patients with intracerebral nonaneurysmal hemorrhage - 6.25%.
      Initial seizures at the onset of subarachnoid hemorrhage is an unfavorable
      prognostic criteria and is associated with higher mortality. Localization of
      aneurysm in anterior part of Willi's Circle and lateral localisation of
      intracerebral hemorrhage are associated with a higher risk of the ASS
      development.

PMID- 30099426
TI  - Epigallocatechin-3-gallate prevents disruption of connective tissue in
      periodontium and salivary glands of rats during systemic inflammation.
AB  - OBJECTIVE: Introduction: The connective tissue remodeling is essential for
      periodontal and salivary glands (SG) pathology. Recently there has been
      demonstrated the number of pharmacological effects of green tea (Camellia
      sinensis) such as antioxidant, anti-inflammatory, anti-aging, antibacterial,
      antiviral and DNA-protective effects, associated with the presence of
      epigallocatechin-3-gallate (EGCG) as an inducer of the Keap1 / Nrf2 / antioxidant
      response element signaling pathway. However, the EGCG effects on the components
      of soft connective tissues of periodontium and SG are still unclear. The aim: To
      investigate the effect of EGCG on markers of disruption of periodontal and
      submandibular SG connective tissues in rats during the conditions of experimental
      systemic inflammation (SI). PATIENTS AND METHODS: Materials and methods: The
      studies were conducted on 30 white rats of the Wistar line, divided into 3
      groups: the 1st included intact animals, the 2nd was made up of animals after
      induced SI (by intraperitoneal administration of lipopolysaccharide Salmonella
      typhi), and the 3rd included animals, which were injected EGCG (production of
      Sigma-Aldrich, Inc., USA) intraperitoneally in a dose of 21.1 mg / kg 3 times a
      week, starting on the 30th day of SI induction. The level of collagenolysis was
      assessed by the content of free hydroxyproline (FHP). The process of
      depolymerization of proteoglycans and sialoglycoproteins was evaluated by
      determining their monomers, glycosaminoglycans (GAGs) and N-acetylneuraminic acid
      (NANA) respectively. The molar roots exposure index (MREI) was calculated.
      RESULTS: Results: Administering EGCG reduced the content of FHP by 33.3 %
      (p<0.01), the content of GAGs by 39.4% (p<0.02), and content of NANA by 34.3%
      (p<0.001) in the soft periodontal tissues compared with the relevant findings in
      the second group of the animals. In this condition the concentration of these
      compounds in the calcified components of periodontium (alveolar bone) lowered as
      well: FHP - by 41.9% (p<0.001), GAGs - by 41.0% (p<0.001), NANA - by 53.3%
      (p<0.001), MREI reduced to 27.1+1.6, i.e. by 27.7% (p<0.01) compared with the
      relevant findings in the second group of the animals. The administration of EGCG
      also reduced the content of FHP by 37.8% (p<0.001), the content of GAGs by 39.8%
      (p<0.001), and the content of NANA by 37.6% (p<0.001) in SG tissues compared with
      the relevant results of the second group of the animals. CONCLUSION: Conclusions:
      The administration of EGCG under modeled systemic inflammation is an effective
      means of preventing and correcting the disruption of connective tissue of
      periodontium and submandibular salivary glands in rats: it reduces collagenolysis
      and depolymerization of proteoglycans and glycoproteins.

PMID- 30099427
TI  - [First aid education - a questionnaire survey].
AB  - OBJECTIVE: Introduction: The ability to provide first aid, especially
      cardiopulmonary resuscitation (CPR) in accordance with the guidelines of the
      European Resuscitation Council (ERC) is a key element in helping and rescuing
      people with pre-hospital cardiac arrest. As recommended by the ERC 2015
      guidelines, one of the most important steps to be taken to increase the rate of
      CPR appraisal by participants or cardiac arrest witnesses is to teach these
      skills to all children in schools. Numerous studies have shown that school-age
      children are positive about learning resuscitation, and moreover, they are
      important multipliers of knowledge because they are happy to transmit the
      information they receive to family members and the closest surroundings. The aim:
      To get to know the opinions of young people about the need for first aid
      education and the period in which it is best to start learning in this area.
      PATIENTS AND METHODS: Materials and methods: The study was attended by 498
      people, students of various types of universities, the research method was an
      online diagnostic survey, a self-help questionnaire tool. RESULTS: Results: The
      study involved 309 women (62%) and 189 (38%) men. The respondents are young
      people between 18-30. Almost all respondents (97.2%) are of the opinion that
      learning first aid should be compulsory in the course of school education. The
      majority of respondents (76.7%) expressed the opinion that the knowledge
      regarding first aid should be updated, 16.3% had no opinion on this subject,
      while only 7.0% of respondents believed that there was no need to do so. Almost
      half of respondents (48.3%) are of the opinion that learning first aid should
      take place from the elementary school, while 30.3% of respondents think that they
      should be educated at pre-school age. CONCLUSION: Conclusions: The vast majority
      of respondents consider first aid education to be significant and needed during
      education. Young people are aware of the need to practice skills and to repeat
      and update information on first aid. The majority of respondents are of the
      opinion that education in this area should be started very early, even in the pre
      school period.

PMID- 30099428
TI  - [The reactions of lipid's free radical oxidation, hemocoagulant properties of
      oral fluid in patients with galvanic currents in the mouth].
AB  - OBJECTIVE: Introduction: Oral manifestation of galvanic currents due to the
      presence of two and more dissimilar metals in dental restorations is rather
      important in prosthodontics. The aim of our study was to assess the reactions
      lipid's free radical oxidation and hemocoagulant properties of oral fluid in
      patients with disorders in oral cavity due to galvanic currents. PATIENTS AND
      METHODS: Materials and methods: The study had got some groups. The first one
      consisted of 7 healthy patients without dental prosthesis. The other one included
      22 patients with dental prosthesis and they were suffered from short circuiting
      due dissimilar metallic restorations in oral cavity. This group we were divided
      into two groups: the second one - for 7 patients were produced metal ceramic
      fixed dental prosthesis, the third one - for 15 patients were produced whole
      casted fixed dental prosthesis and pressing brazed fixed dental prosthesis. To
      assess the process of lipid's free radical oxidation of oral fluid we studied
      kinetic concentration of malone dialdehyde, activity level of superoxide
      dismutase and catalase. Also we found out hemocoagulant activity data of oral
      fluid: thrombin time, prothrombin time, fibrinolytic activity, recalcification
      time. RESULTS: Results: In our study we observed increasing of lipid's free
      radical oxidation in patients of the second and third groups, which led to
      increasing malone dialdehyde data in third group compared with second group. In
      patients of second and third groups was recorded the increasing of the CAT
      activity in the oral fluid. Also there is the in fact decreasing in hemocoagulant
      properties of oral fluid, such as reducing in recalcification time, increasing in
      prothrombin time in the second and especially in the third groups of patients. It
      was marked the significant increasing of fibrinolytic activity of oral fluid in
      the second and third group of patients. CONCLUSION: Conclusions: The oral
      manifestation of electrochemical interactions due to presence of dissimilar
      metallic restorations led to shift in oral cavity's homeostasis. This statement
      we can verify with results of our study. In patients with oral manifestation of
      galvanic currents were observed the increasing in activity of the reactions of
      lipid's free radical oxidation in oral fluid, changes in antioxidative enzymes
      and in local homeostasis of oral fluid.

PMID- 30099429
TI  - Dynamics of epidemiological indications of epilepsy prevalence, morbidity and
      disability among children in kharkiv region, Ukraine.
AB  - OBJECTIVE: Introduction: According to the World Health Organization, epilepsy is
      one of the most common diseases of the central nervous system, which affects 0.5
      to 2% of the entire population The aim is comparison of prevalence, incidence and
      disability from nervous diseases and epilepsy among children of the Kharkiv
      region of Ukraine and the results are compared with global figures. PATIENTS AND
      METHODS: Materials and methods: Epidemiological indicators, namely the prevalence
      and incidence. For the comparative analysis, the statistical data of the last 5
      years are used. RESULTS: Review: The prevalence of epilepsy in Ukraine amounts to
      25 695 children (3.21%), higher than the prevalence of cerebral palsy or
      neuroinfections, the average value for 5 years is 24 667 children (3.144%). In
      the Kharkiv region the number is 1 451 children (3.43%), 5-year average is 1 340
      children (3.21%). The incidence of epilepsy in children in Ukraine is 3 306
      children (0.43%), the average value for 5 years is 3 569 children (0.454%). In
      Kharkiv region the incidence is 252 persons (0.53%), an average is 201.2 children
      (0.468%). CONCLUSION: Conclusions: Reliable epidemiological indicators will make
      it possible to improve the system of rendering specialized medical care to
      children with epilepsy, carry out a pharmaco-economic analysis, calculation and
      estimation of the costs for patients' treatment, which is especially important in
      the framework of the health care system reformation. Thus, the compilation of
      patients' registers with epilepsy is one of the urgent tasks to optimize the
      medical care.

PMID- 30099430
TI  - [Practical aspects of the use of botulinum toxin in the treatment of idiopathic
      overactive bladder].
AB  - Idiopathic overactive bladder due to its high impact on quality of life and high
      prevalence is a significant problem in everyday clinical practice. Currently, we
      do not have medicines that allow patients to be cured completely. Therapy is
      focused on the elimination or reduction of symptoms. An established position in
      the treatment of this disease for many years has a botulinum toxin. This therapy
      is used in patients whose conservative methods have not improved or are not
      acceptable because of side effects. The therapeutic effect after the injection of
      bladder detrusor muscle is limited in time and does not occur in all patients.
      Patients who benefit from this therapy require repeated procedures to reduce the
      symptoms of the disease. Many authors modify the standard treatment protocol of
      botulinum toxin in idiopathic overactive bladder in search of better results. The
      main goal is to improve the efficiency and extend the duration of the drug while
      reducing side effects. Undoubtedly, the technique of botulinum toxin injection
      has an effect on the final effect of treatment. The location and depth of
      punctures, the dose of the drug, preparation of the drug solution, periprocedural
      management and prophylaxis, and observation of the patient after the procedure
      are some issues whose modifications in the literature have been studied in order
      to achieve additional benefits from this therapy. In our work, we discuss the
      technical and practical aspects of this procedure in the search for the most
      optimal treatment protocol with the use of botulinum toxin in the treatment of
      idiopathic overactive bladder.

PMID- 30099431
TI  - Screening and periodical medical examinations as important part of public health:
      problem of the legal implementation.
AB  - OBJECTIVE: Introduction: Public health is an important concept, which is
      continually being globalized and integrated into today's society. It helps to
      improve and prolong the quality of life of people and prevent the spread of
      epidemics and serious incurable diseases. The components of public health include
      protection, prevention, and promotion. Prevention, the measures taken to prevent
      disease as opposed to treatment consist of screening and periodical medical
      examinations. There are two types of screening- universal screening and case
      finding (individual screening). Universal screening and periodical medical
      examination are identical concepts; the terms dispensary and individual screening
      (case finding) have similar meanings and can be used interchangeably. These
      concepts and their importance are analyzed in this research. The aim: A research
      on the legal regulation of periodic health examinations and screening as a two
      systems, which provides the implementation of prevention within the public
      health. Analysis of foreign experience such countries as: Great Britain, USA,
      Austria, Germany, Australia, France, Italy and others. PATIENTS AND METHODS:
      Materials and methods: The research based on: Ukrainian legislation, European
      Union's Law Acts, decisions of the ECHR, EU's member-states law, WHO Acts and
      Recommendations, scientific articles. The research is also based on general
      scientific and special research methods (such as dialectical, comparative,
      analytic, synthetic). RESULTS: Review: In Europe (except Germany and Austria) is
      happening the transition from the system of mandatory periodical medical
      examination to new screening system. However, despite this, periodical medical
      examinations of Europeans held in connection with exist system health insurance
      (both voluntary and mandatory). CONCLUSION: Conclusions: Screening and periodical
      medical examinations are two of the most important aspects of public health as
      they help to diagnose diseases at an early stage, even before showing any
      symptoms. Screening and periodical medical examinations ensures the safety and
      health of the entire population as opposed to certain individuals and therefore
      be mandatory procedure in today's society.

PMID- 30099432
TI  - Criteria of economic effectiveness of preventive measures of chronic non
      infectious diseases.
AB  - OBJECTIVE: Introduction: Today, Ukraine is among the five largest European
      countries in terms of population, ranking fifth after Germany, Great Britain,
      France and Italy. Over the past decades, the number of people in Ukraine has been
      decreasing, mainly due to the excess of deaths over births. The high mortality
      rate in Ukraine is burdened by the fact that it concerns people of working age -
      the standardized mortality rate of the working-age population is 2.4 times higher
      than that of the EU countries and 1.5 times the average in Europe. The aim of
      this article was to determine the rationale for the economic effectiveness of the
      prevention of chronic non-communicable diseases and criteria for calculating the
      economic forecast. PATIENTS AND METHODS: Materials and methods: The research was
      conducted with the help of theoretical and statistical methods, by studying
      scientific sources and systematic analysis and generalization of the experience
      of finding economic efficiency of preventive measures of chronic diseases.
      CONCLUSION: Review and conclusions: The analysis of the considered methods of
      economic evaluation of the prevention and treatment of chronic non-infectious
      diseases made it possible to draw the following conclusions that the
      effectiveness of the health care system and individual health care facilities
      should be considered in a complex manner from the point of view of medical,
      social and economic efficiency. Economic efficiency, as a rule, is the result of
      medical and social efficiency. When calculating the cost-effectiveness of
      treatment and prevention measures, the whole complex of losses and costs
      associated with illnesses should be taken into account, in particular: direct
      costs directly related to preventionand treatment; Indirect losses associated
      with the illness, due to the unprocessed part of the gross domestic product, paid
      by sick leave. The task of the economic substantiation of medical and preventive
      measures is to calculate the necessary volume of material and technical and
      financial resources, as well as their effective use.

PMID- 30099433
TI  - [ROLA I WARTOSC ROKOWNICZA MIKROKRWAWIEN MOZGOWYCH W SCHORZENIACH NEUROLOGICZNYCH
      THE ROLE AND PROGNOSTIC VALUE OF CEREBRAL MICROBLEEDS IN NEUROLOGICAL DISORDERS
      907].
AB  - Cerebral microbleeds (CMB) are small foci of low signal which are detected in
      neuroimaging. They correspond to hemosiderin and other blood breakdown products
      from brain vessels whose structure was affected by pathological processes. Their
      pathogenesis is closely related to angiopathy associated with hypertension and
      cerebral amyloid angiopathy. Microbleeds occur in a completely healthy population
      as well as in numerous neurological disorders. They are often present in people
      afflicted with dementia, in the course of neurodegenerative diseases and due to
      vascular causes. Their prevalence is also higher in people with ischemic stroke
      and in non-traumatic intracerebral bleeding. The presence of microbleeds is
      reflected in the prognosis of the patients, the presence of complications of
      treatment, and the occurrence of the disease entities in previously healthy
      people. They also affect the emotional state and quality of life of patients. We
      will try to summarize the current state of knowledge regarding the relationship
      between microbleeds and neurological disorders and present their potential
      predictive value.

PMID- 30099434
TI  - Obesity during pregnancy: literature review.
AB  - OBJECTIVE: Introduction: Maternal obesity is a serious problem in obstetric
      gynecological practice in the world. Pathophysiological changes create conditions
      for obstetric and perinatal complications, the most important complications of
      which is gestational diabetes mellitus, preeclampsia, pathological course of
      labor, increased operative delivery, fetal distress. The aim of the study is to
      find out the depth of the problem "Obesity and Pregnancy" by analyzing the range
      of obstetric, perinatal complications based on the processing of scientific
      relevant literature data. PATIENTS AND METHODS: Materials and methods: An
      analysis of international and national scientific literature on the problem of
      pregnancy has been made. Methods used: bibliographic, scientific research,
      synthetic, analytical and generalizing. CONCLUSION: Review and conclusions:
      Taking into account the high risk of maternal and perinatal complications
      associated with obesity, it is necessary to develop therapeutic and diagnostic
      measures and implement dynamic monitoring of pregnant women to minimize these
      risks.

PMID- 30099435
TI  - Emphysematous pyelonephritis - a rare complication of diabetes mellitus.
AB  - Emphysematous pyelonephritis is a rare form of acute necrotizing pyelonephritis.
      It is a gas-producing, necrotizing infection involving the renal parenchyma and
      surrounding tissues. It is associated with high mortality and morbidity. In the
      majority of cases, patients with long-standing diabetes and poor glycemic control
      are affected. We report the case of a 67 yr old female who survived severe sepsis
      due to emphysematous pyelonephritis. Potential therapeutic strategies in the
      aftermath from a diabetologist's point of view are discussed.

PMID- 30099436
TI  - Treatment algorithms of patients with impaction of maxillary central incisors
      caused by supernumerary teeth.
AB  - OBJECTIVE: Introduction: Supernumerary teeth, like etiological factor of
      impaction, occur in 7,05% of patients, are usually located in anterior maxillary
      region - 93,2%. The aim of the study is to develop an algorithm of treatment of
      patients with impaction of permanent maxillary central incisors, caused by
      supernumerary teeth, during periods of mixed and permanent dentition by
      processing our own approaches to treatment. PATIENTS AND METHODS: Materials and
      methods: Treatment results of seven patients (6, 7 (2 patients), 8, 9, 10 and 15
      years old) with delay in eruption of maxillary central incisors were analyzed.
      According to the results of clinical and additional examination methods
      (photometric examination of face, study of diagnostic models of jaws and
      orthopantomograms, 3D computed tomography), impacted central incisors,
      supernumerary teeth, blocking their eruption, were diagnosed. RESULTS: Results:
      Clinical experience of treatment of patients with impacted teeth caused by
      presence of supernumerary teeth in the jaws, allowed us to propose algorithms of
      providing complex treatment in such cases, depending on physiological state of
      occlusion - mixed or permanent, and depth of supernumerary tooth location.
      CONCLUSION: Conclusions: If there are no central incisors in the dental arch
      after the term of their physiological eruption, orthopantomogram must be taken to
      confirms or reject tooth impaction, and then 3D computed tomography should be
      done to show accurate localization of the tooth and only after these stages it is
      possible to choose the treatment plan. Patients with impacted maxillary central
      incisors caused by supernumerary teeth should undergo orthodontic treatment in
      several stages.

PMID- 30099437
TI  - Mortality Effects of Prolonged Hemoperfusion Therapy Using a Polymyxin B
      Immobilized Fiber Column for Patients with Septic Shock: A Sub-Analysis of the
      DESIRE Trial.
AB  - BACKGROUND/AIMS: The optimal duration of hemoperfusion therapy with a polymyxin B
      immobilized fiber column has not yet been verified. METHODS: This analysis
      examined whether hemoperfusion therapy with a polymyxin B-immobilized fiber
      column lasting longer than 2 h (prolonged polymyxin) improved outcomes for
      patients with septic shock compared to 2-h polymyxin therapy (sub-analysis of
      data from the DESIRE trial). RESULTS: The 2-h and prolonged polymyxin groups
      contained 22 and 14 patients, respectively. Both groups had similar
      characteristics. The polymyxin duration per session in the prolonged polymyxin
      group was significantly longer (median, 5.5 h) than in the 2-h polymyxin group (p
      < 0.01). The 28-day mortality rate was significantly higher in the 2-h polymyxin
      group (7, 31.8%) than in the prolonged polymyxin group (0, 0%; p = 0.019).
      CONCLUSION: Prolonged polymyxin therapy might be associated with better clinical
      outcomes than 2-h polymyxin therapy in patients with septic shock. Video Journal
      Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=491744.

PMID- 30099438
TI  - Disassembly of Subplasmalemmal Actin Filaments Induces Cytosolic Ca2+ Increases
      in Astropecten aranciacus Eggs.
AB  - BACKGROUND/AIMS: Eggs of all animal species display intense cytoplasmic Ca2+
      increases at fertilization. Previously, we reported that unfertilized eggs of
      Astropecten aranciacus exposed to an actin drug latrunculin A (LAT-A) exhibit
      similar Ca2+ waves and cortical flashes after 5-10 min time lag. Here, we have
      explored the molecular mechanisms underlying this unique phenomenon. METHODS:
      Starfish eggs were pretreated with various agents such as other actin drugs or
      inhibitors of phospholipase C (PLC), and the changes of the intracellular Ca2+
      levels were monitored by use of Calcium Green in the presence or absence of LAT
      A. The concomitant changes of the actin cytoskeleton were visualized with
      fluorescent F-actin probes in confocal microscopy. RESULTS: We have shown that
      the LAT-A-induced Ca2+ increases are related to the disassembly of actin
      flaments: i) not only LAT-A but also other agents depolymerizing F-actin (i.e.
      cytochalasin B and mycalolide B) induced similar Ca2+ increases, albeit with
      slightly lower efficiency; ii) drugs stabilizing F-actin (i.e. phalloidin and
      jasplakinolide) either blocked or significantly delayed the LAT-A-induced Ca2+
      increases. Further studies utilizing pharmacological inhibitors of PLC (U-73122
      and neomycin), dominant negative mutant of PLC-gamma, specific sequestration of
      PIP2 (RFP-PH), InsP3 uncaging, and quantitation of endogenous InsP3 all indicated
      that LAT-A induces Ca2+ increases by stimulating PLC rather than sensitizing
      InsP3 receptors. In support of the idea, it bears emphasis that LAT-A timely
      increased intracellular contents of InsP3 with concomitant decrease of PIP2
      levels in the plasma membrane. CONCLUSION: Taken together, our results suggest
      that suboolemmal actin filaments may serve as a scaffold for cell signaling and
      modulate the activity of the key enzyme involved in intracellular Ca2+ signaling.

PMID- 30099440
TI  - Cardiac Magnetic Resonance Evaluation of the Extent of Myocardial Injury in
      Patients with Inferior ST Elevation Myocardial Infarction and Concomitant ST
      Depression in Leads V1-V3: Analysis from the MITOCARE Study.
AB  - : The aim of our study was to examine the pathophysiology of ST depression (STD)
      in leads V1-V3 in the setting of inferior ST elevation myocardial infarction
      (iSTEMI) through the perspective of cardiac magnetic resonance (CMR). METHODS:
      Differences in myocardial area at risk (MaR), infarct size, ejection fraction and
      myocardial segment involvement by CMR were compared in MITOCARE trial patients
      with first iSTEMI with ST elevation (STE), STD or no ST changes (NST) in V1-V3.
      The frontal plane projection of the inferior wall MaR in relationship to the
      anterior/posterior chest wall was calculated and compared between groups.
      RESULTS: Fifty-six patients were included. Patients with STD (n = 38) and STE (n
      = 5) in V1-V3 had significantly larger mean MaR compared to NST (n = 13; 32 +/-
      7%LV, 36 +/- 10%LV and 26 +/- 6%LV, respectively; p = 0.01). STD in leads V1-V3
      was associated with more apical inferior and mid inferoseptal involvement and had
      a larger mean frontal plane projection of MaR compared with NST (24 +/- 6%LV vs.
      20 +/- 6%LV, p = 0.04). CONCLUSION: STD in V1-V3 in iSTEMI is associated with
      larger MaR, more extension into the inferoseptal segments and likely results from
      greater frontal plane projection of the MaR, leading to reciprocal changes on the
      electrocardiogram.

PMID- 30099439
TI  - Combined Immunosuppressive Treatment May Improve Short-Term Renal Outcomes in
      Chinese Patients with Advanced IgA Nephropathy.
AB  - BACKGROUND/AIMS: Treatment of advanced Immunoglobulin A nephropathy (IgAN)
      patients with estimated glomerular filtration rate (eGFR) below 45 mL/min per
      1.73 m2 remains inconsistent. The aim of this study is to compare the effects of
      corticosteroid and immunosuppressant therapies among these patients. METHODS: A
      total of 201 adult patients with advanced IgAN (eGFR < 45 mL/min/1.73 m2 and
      proteinuria > 1 g/24h at biopsy) grouped into supportive care (SC), steroids
      alone (CS), and steroids plus immunosuppressant (IT) groups, were investigated
      between 30th December 2002 and 30th June 2016. The primary endpoint was the
      combined endpoint of a 50% decline in eGFR and/or end stage renal disease (ESRD:
      eGFR < 15 mL/min/1.73 m2 or maintenance renal replacement treatment). Responses
      to therapy included complete remission (CR: urinary protein excretion < 0.5
      g/24h, with eGFR decrease less than 10% baseline), partial remission (PR:
      proteinuria decrease by > 50% baseline, with eGFR decrease less than 10%
      baseline), no response (NR: proteinuria decrease < 50% baseline, or eGFR decrease
      > 10% baseline) and ESRD. Kaplan-Meier and Cox proportional hazards analyses were
      performed. RESULTS: During the follow-up period (37.2 +/- 22.7 months), 6.8%
      patients in SC group, 25.0% in CS group, and 38.0% in IT group achieved CR or PR,
      while 78.4%, 62.5% and 49.3% patients in these 3 groups reached primary endpoint
      respectively (p < 0.001). Three-year renal survival rates in SC and combined
      immunosuppressive treatment groups (CS and IT groups) were 33.8% vs 51.2% (p =
      0.02), and 5-year renal survival rates were 12.2% vs 21.3% (p = 0.1)
      respectively. Multivariate Cox regression analysis showed that hypertension (HR =
      2.44, 95% CI 1.51-3.95; p < 0.001), Scr (HR = 1.01, 95% CI 1.00-1.01; p < 0.001),
      T1-T2 lesion (HR = 1.99, 95% CI 1.35-2.93; p = 0.001) were independent indicators
      of poor renal outcome. CONCLUSION: Immunosuppressive treatment (CS and IT
      therapy) may improve short-term renal outcome compared with supportive treatment
      in advanced IgAN patients.

PMID- 30099441
TI  - Daclatasvir Plasma Levels in a Cohort of Patients with Hepatitis C Virus
      Infection Taking Methadone: A Prospective Analysis.
AB  - : Backround: The effect of methadone (MET) during therapy with novel direct
      acting antiviral agents is still not fully understood. Currently, no data are
      available about the influence of MET on daclatasvir (DCV) plasma levels in
      patients affected by chronic hepatitis C (CHC). The aim of this study was to
      assess the DCV plasma concentrations in patients treated with sofosbuvir (SOF)
      plus DCV, with or without ribavirin (RBV) and with or without MET. METHODS: In
      this analysis, 47 patients were included, treated consecutively with SOF + DCV +/
      RBV for 24 weeks, from May to October 2015; 22 (46.8%) received MET substitutive
      therapy. RESULTS AND CONCLUSION: We found a significant difference in DCV levels
      at 2 weeks and 1 month: 150 ng/mL in patients without MET and 313 ng/mL with MET
      at 2 weeks (p < 0.001), 149 and 279 ng/mL at 1 month (p = 0.006). DCV levels were
      lower in cirrhotic patients (p < 0.001); among cirrhotic patients we also
      evidenced higher DCV concentrations in patients receiving MET at 2 weeks, 1 and 2
      months (p < 0.001, p = 0.005, and p = 0.031, respectively). In multivariate
      analysis, the only predictive factor associated with DCV plasma levels was the
      presence of MET. The reason for this increased DCV exposure is unclear; on the
      clinical side, we have not observed significant adverse events related to the
      reduction or increase of MET plasma levels. The administration of MET in patients
      with advanced fibrosis or cirrhosis leads to an early increase of DCV plasma
      level without significant clinical effects or toxicity.

PMID- 30099442
TI  - Mir-758-5p Suppresses Glioblastoma Proliferation, Migration and Invasion by
      Targeting ZBTB20.
AB  - BACKGROUND/AIMS: To determine the cellular functions and clinical significance of
      micro-758-5p (miR-758-5p) in glioblastoma (GBM) by targeting zinc finger and BTB
      domain-containing protein 20 (ZBTB20). METHODS: Fifty-five paired GBM tissues and
      adjacent normal tissues, GBM cell lines (U118, LN-299, H4, A172, U87-MG, and
      U251), and normal human astrocyte cell line (HEB) were used. miR-758-5p mimics,
      ZBTB20 siRNA, and pcDNA3.1-ZBTB20 were transiently transduced into cancer cells
      independently or together. qRT-PCR was conducted to analyze the expression of miR
      758-5p and ZBTB20. Luciferase reporter assays were performed to determine the
      effect of miR-758-5p on ZBTB20. Western blot was applied to measure the
      expression of ZBTB20, PCNA, and cleaved caspase3. Cell Counting Kit-8 (CCK8),
      colony formation, FACS, and Transwell assays were carried out to detect cellular
      proliferation, apoptosis, migration, and invasion. Xenograft experiments were
      implemented to evaluate tumor growth and metastasis in vivo. RESULTS: miR-758-5p
      was significantly downregulated in GBM tissues and cell lines compared with that
      in adjacent normal tissues and HEB cells. miR-758-5p overexpression inhibited the
      proliferation, migration, and invasion of GBM cells and induced apoptosis by
      regulating the ZBTB20 expression. Pearson correlation analysis also confirmed
      that miR-758-5p was inversely correlated with ZBTB20 in GBM tissues. miR-758-5p
      suppressed tumor growth and metastasis in vivo. The restored ZBTB20 expression
      partially rescued the miR-758-5p-induced inhibition of GBM cell proliferation,
      migration, and invasion. Kaplan-Meier curve analysis revealed that a high miR-758
      5p expression indicated an enhanced prognosis of patients with GBM. CONCLUSION:
      miR-758-5p suppressed GBM progression by targeting ZBTB20. The miR-758-5p/ZBTB20
      axis might be a promising therapeutic target for GBM treatment.

PMID- 30099444
TI  - The Association of Urinary Sodium and Potassium with Renal Uric Acid Excretion in
      Patients with Chronic Kidney Disease.
AB  - BACKGROUND/AIMS: Hypertension and hyperuricemia are closely associated with an
      intermingled cause and effect relationship. Additionally, urinary sodium and
      potassium excretion is related to blood pressure. Whether or not it is associated
      with urinary uric acid excretion is not clear. Therefore, we aim to study the
      association of urinary sodium and potassium with renal uric acid excretion in
      patients with CKD. METHODS: A cross-sectional study of 428 patients with CKD
      recruited from our department was conducted. All patients were divided into
      hypertension and non-hypertension group. In these two groups, Spearman
      correlation and multiple linear regression analysis were used to study the
      correlation of urinary sodium and potassium with renal handling of uric acid.
      RESULTS: According to multiple linear regression analysis, in hypertension group,
      fractional excretion of sodium (FEna) was negatively correlated with 24 hour
      urinary uric acid (24-hUur) and uric acid clearance rate (Cur) (beta coefficients
      [B]=-0.066, -0.182, respectively; both P< 0.05), and positively correlated with
      fractional excretion of uric acid (FEur) (B=1.641, P< 0.001). Additionally,
      fractional excretion of potassium (FEk) was positively correlated with FEur
      (B=0.576, P< 0.001), but not related to 24-hUur and Cur (both P>0.05). And
      urinary sodium/potassium ratio (Una/k) was negatively related to 24-h Uur and Cur
      (B=-0.047, -0.159, both P< 0.05), and positively related to FEur (B=0.578, P<
      0.05). Furthermore, FEna and FEk was still positively related to FEur in the
      lowest tertile of eGFR groups (both P< 0.05), but not related in the second and
      highest tertile of eGFR groups (all P> 0.05). In non-hypertension group, FEna was
      negatively correlated with 24-hUur (B=-0.589, P< 0.05), but not related to Cur
      and FEur (both P> 0.05). both FEk and Una/k was not related to 24-h Uur, Cur and
      FEur (all P> 0.05). Moreover, FEna and FEk was still not correlated with FEur in
      all tertiles of eGFR groups (all P> 0.05). CONCLUSION: We found that in patients
      with CKD, urinary sodium and potassium excretion is closely correlated to renal
      handling of uric acid, which was pronounced in hypertensive patients with low
      eGFR. This phenomenon may be one of the mechanisms of the relationship between
      hypertension and hyperuricemia. Further research is needed to confirm it. It is
      expected to manage hyperuricemia in terms of controlling the diet of sodium and
      potassium.

PMID- 30099443
TI  - Dihydroartemisinin Increases the Sensitivity of Photodynamic Therapy Via NF
      kappaB/HIF-1alpha/VEGF Pathway in Esophageal Cancer Cell in vitro and in vivo.
AB  - BACKGROUND/AIMS: Although photodynamic therapy (PDT) can relieve esophageal
      obstruction and prolong survival time of patients with esophageal cancer, it can
      induce nuclear factor-kappa B (NF-kappaB) activation in many cancers, which plays
      a negative role in PDT. Dihydroartemisinin (DHA), the most potent artemisinin
      derivative, can enhance the effect of PDT on esophageal cancer cells. However,
      the mechanism is still unclear. METHODS: We generated stable cell lines
      expressing the super-repressor form of the NF-kappaB inhibitor IkappaBalpha and
      cell lines with lentivirus vector-mediated silencing of the HIF-1alpha gene.
      Esophageal xenograft tumors were created by subcutaneous injection of Eca109
      cells into BALB/c nude mice. Four treatment groups were analyzed: a control
      group, photosensitizer alone group, light alone group, and PDT group. NF-kappaB
      expression was detected by an electrophoretic mobility shift assay, hypoxia
      inducible factor alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF)
      by real-time PCR, NF-kappaB, HIF-1alpha, and VEGF protein by western blot, and Ki
      67, HIF-1alpha, VEGF, and NF-kappaB protein by immunohistochemistry. RESULTS: PDT
      increased NF-kappaB activity and the gene expression of HIF-1alpha and VEGF in
      vitro and in vivo. In contrast, the DHA groups, particularly the combined DHA and
      PDT treatment group, abolished the effect. The combined treatment significantly
      inhibited tumor growth in vitro and in vivo. NF-kappaB activity and HIF-1alpha
      expression were also reduced in the stable IkappaBalpha expression group, whereas
      the former showed no change in HIF-1alpha-silenced cells. CONCLUSION: DHA might
      increase the sensitivity of esophageal cancer cells to PDT by inhibiting the NF
      kappaB/HIF-1alpha/VEGF pathway.

PMID- 30099446
TI  - Gynecologic Oncologists' Perceptions of Palliative Care and Associated Barriers:
      A Survey of the Society of Gynecologic Oncology.
AB  - OBJECTIVES: Gynecologic oncologists frequently care for patients at the end of
      life with the aid of palliative care (PC) specialists. Our primary objectives
      were to identify perceived barriers to integrating specialty PC into gynecologic
      cancer care. MATERIALS AND METHODS: Members of the Society of Gynecologic
      Oncology (SGO) were invited to participate in an anonymous online survey. A
      Likert scale captured perceptions regarding primary and specialty PC, frequent
      barriers to use of PC, and potential interventions. RESULTS: A total of 174 (16%)
      gynecologic oncologists completed the survey. The majority (75%) agreed or
      strongly agreed that PC should be integrated into cancer care at diagnosis of
      advanced or metastatic cancer. The most frequently perceived PC barriers included
      patients' unrealistic expectations (54%), limited access to specialty PC (25%),
      poor reimbursement (25%), time constraints (22%), and concern of reducing hope or
      trust (21%). The most agreed upon potential intervention was increased access to
      outpatient PC (80%). CONCLUSIONS: According to this cohort of SGO members,
      families' or patients' unrealistic expectations are the most frequent barriers to
      specialty PC. Understanding this communication breakdown is critically important.

PMID- 30099445
TI  - Independent Association of Overhydration with All-Cause and Cardiovascular
      Mortality Adjusted for Global Left Ventricular Longitudinal Systolic Strain and
      E/E' Ratio in Maintenance Hemodialysis Patients.
AB  - BACKGROUND/AIMS: Fluid overload is common and associated with morbidity and
      mortality in patients with end-stage renal disease. The relationship between
      fluid overload and cardiac function is complex, and whether fluid overload is
      associated with adverse outcomes in patients undergoing hemodialysis (HD)
      independently of systolic and diastolic function of the left ventricle (LV)
      remains unclear. METHODS: The present study aimed to investigate the relationship
      between overhydration and all-cause and cardiovascular (CV) mortality after
      adjusting for LV function in 178 maintenance HD patients. The relative hydration
      status (overhydration/ extracellular water, ?HS) was measured using a body
      composition monitor, and then used to assess the fluid status. A ?HS >=7% was
      defined as fluid overload. Global left ventricular longitudinal systolic strain
      (GLS), and the early filling and early diastolic mitral annular velocity (E/E')
      ratio were assessed using speckle-tracking and tissue Doppler echocardiography.
      RESULTS: During a mean follow-up period of 2.7 years, 24 patients died, including
      11 CV deaths. An increased ?HS was significantly associated with all-cause and CV
      mortality in the univariate analysis. This prognostic significance remains after
      multivariate adjusting for GLS and E/E' ratio for all-cause (HR, 1.123; 95% CI,
      1.063-1.186; p-value < 0.001) and CV (HR, 1.088; 95% CI, 1.005-1.178; p-value
      =0.037) mortality. Moreover, ?HS significantly improved the prognostic value
      beyond conventional clinical and echocardiographic parameters. CONCLUSION: A
      higher ?HS was independently associated with increased all-cause and CV mortality
      after adjusting for systolic and diastolic function of the LV. This suggests that
      ?HS may be a relevant target for improving outcomes in maintenance HD patients.

PMID- 30099447
TI  - Emodin and Its Combination with Cytarabine Induce Apoptosis in Resistant Acute
      Myeloid Leukemia Cells in Vitro and in Vivo.
AB  - BACKGROUND/AIMS: Acute myeloid leukemia (AML) remains a hematologic malignancy
      with poor survival and a high risk of relapse, which is mainly caused by the
      emergence of multidrug resistance (MDR). The identification of novel agents to
      improve therapeutic strategies becomes important priority for AML treatment. It
      has been shown that emodin has therapeutic effects on many kinds of human
      malignant tumors. In this study, we investigated the anti-leukemia effects of
      emodin alone or in combination with cytarabine (Ara-C) on multidrug-resistant AML
      HL-60/ADR cells and in a mouse xenograft model of human highly tumorigenic AML HL
      60/H3 cells. The underlying mechanism was also addressed. METHODS: Cell viability
      after treatment was measured by MTT assay. The DNA fragmentation assay, Annexin V
      PE/7-AAD, AO/EB staining, and electron microscopy were introduced to assess the
      apoptotic induction effects. Changes in protein expression in the Akt and ERK
      signaling pathways were determined by western blotting. In vivo antileukemia
      effects on HL-60/H3 xenograft model and overall mouse survival outcomes were
      further analyzed in this study. RESULTS: Emodin dose-dependently induced growth
      inhibition and apoptotic effects in resistant HL-60/ADR cells in vitro as well as
      in the HL-60/H3 xenograft models in vivo. Moreover, emodin significantly enhanced
      chemosensitivity of AML cells to Ara-C, inhibited leukemic cell growth, and
      improved survival in the mouse xenograft model of AML. Dual targeting of Akt and
      ERK signaling pathways might contribute to the anti-leukemia effects on AML cells
      in vitro and in vivo. CONCLUSION: Emodin and its combination with Ara-C may be
      considered a promising therapeutic approach in AML and worthy of further
      investigation.

PMID- 30099448
TI  - Lipopolysaccharides (LPS) Induced Angiogenesis During Chicken Embryogenesis is
      Abolished by Combined ETA/ETB Receptor Blockade.
AB  - BACKGROUND/AIMS: Angiogenesis plays a key role during embryonic development. The
      vascular endothelin (ET) system is involved in the regulation of angiogenesis.
      Lipopolysaccharides (LPS) could induce angiogenesis. The effects of ET blockers
      on baseline and LPS-stimulated angiogenesis during embryonic development remain
      unknown so far. METHODS: The blood vessel density (BVD) of chorioallantoic
      membranes (CAMs), which were treated with saline (control), LPS, and/or BQ123 and
      the ETB blocker BQ788, were quantified and analyzed using an IPP 6.0 image
      analysis program. Moreover, the expressions of ET-1, ET-2, ET3, ET receptor A
      (ETRA), ET receptor B (ETRB) and VEGFR2 mRNA during embryogenesis were analyzed
      by semi-quantitative RT-PCR. RESULTS: All components of the ET system are
      detectable during chicken embryogenesis. LPS increased angiogenesis
      substantially. This process was completely blocked by the treatment of a
      combination of the ETA receptor blockers-BQ123 and the ETB receptor blocker
      BQ788. This effect was accompanied by a decrease in ETRA, ETRB, and VEGFR2 gene
      expression. However, the baseline angiogenesis was not affected by combined
      ETA/ETB receptor blockade. CONCLUSION: During chicken embryogenesis, the LPS
      stimulated angiogenesis, but not baseline angiogenesis, is sensitive to combined
      ETA/ETB receptor blockade.

PMID- 30099449
TI  - Rotenone Protects Against Acetaminophen-Induced Kidney Injury by Attenuating
      Oxidative Stress and Inflammation.
AB  - BACKGROUND/AIMS: In clinic, excessive acetaminophen (APAP) can cause kidney
      damage with uncertain mechanisms. Recently, accumulating evidence demonstrated a
      pathogenic role of mitochondrial dysfunction in the kidney injury. Thus, in this
      study, rotenone, a mitochondrial complex I inhibitor, was applied to the mice
      with APAP-induced acute kidney injury to evaluate the effect of mitochondrial
      complex I inhibition on APAP nephrotoxicity. METHODS: After 3 days of rotenone
      pretreatment, mice were administered with APAP (300mg/kg) by intraperitoneal
      injection for 24 h. Then the kidney injury, inflammation, and oxidative stress
      were evaluated. RESULTS: APAP significantly enhanced the BUN, serum creatine, and
      cystatin C levels in line with a moderate alteration of renal morphology.
      Strikingly, rotenone treatment normalized BUN, serum creatinine, and cystatin C
      levels, as well as the kidney morphology. Meanwhile, APAP enhanced tubular injury
      markers of NGAL and KIM-1 by 347- and 5-fold at mRNA levels, respectively. By
      Western blotting, we confirmed a 15-fold increment of NGAL in APAP-exposed
      kidneys. Importantly, rotenone treatment largely normalized NGAL and KIM-1 levels
      and attenuated inflammatory response in APAP-treated mice. Similarly, rotenone
      treatment enhanced the expressions of SOD1-3 compared with APAP group in line
      with a significant suppression of kidney MDA content. Finally, we observed that
      inhibition of mitochondrial complex III failed to protect against APAP-induced
      nephrotoxicity. CONCLUSION: Mitochondrial complex I inhibitor rotenone protected
      kidneys against APAP-induced injury possibly via the inhibition of mitochondrial
      oxidative stress and inflammation.

PMID- 30099451
TI  - Icariin Improves Sepsis-Induced Mortality and Acute Kidney Injury.
AB  - OBJECTIVES: Icariin (ICA) is a bioactive flavonoid with renal protective actions.
      This study investigated the effects of ICA on renal injury, inflammation,
      oxidative damage, apoptosis, and survival in a mouse model of cecal ligation and
      perforation (CLP)-induced sepsis. METHODS: Sepsis was induced by CLP. Mice were
      treated with ICA (30 or 60 mg/kg) for 3 days before CLP. Renal functions,
      inflammatory responses, oxidative damage, histological changes, apoptosis, and
      vascular permeability were examined. The effects of ICA on CLP-induced expression
      of renal nuclear factor-kappaB (NF-kappaB), cleaved caspase-3, Bax, and Bcl-2
      were evaluated. RESULTS: Mice in the CLP group had a low survival rate and
      increases in blood urea nitrogen and creatinine levels, proinflammatory cytokine
      levels, oxidative damage, apoptosis, and vascular permeability. These renal
      changes were dramatically improved by ICA treatment, especially in the 60 mg/kg
      ICA group. The detection of molecules involved in the inflammation and apoptosis
      of the kidney indicated that ICA reduced expression of NF-kappaB, cleaved caspase
      3, and Bax but enhanced expression of Bcl-2. CONCLUSION: ICA improves CLP-induced
      mortality and acute kidney injury by inhibiting renal oxidant damage,
      inflammatory responses, apoptosis, and vascular permeability.

PMID- 30099450
TI  - Once-a-Day Trazodone in the Treatment of Depression in Routine Clinical Practice.
AB  - OBJECTIVE: The aim of the study was to evaluate the efficacy, tolerability, and
      safety of once-a day trazodone tablets (Trittico Prolong(r) 300 mg) in patients
      with moderate to severe depression in routine clinical practice. METHODS: Men and
      women >=18 years old with Montgomery-Asberg Depression Rating Scale (MADRS)
      scores > 21 and Clinical Global Impression - Severity (CGI/S) >=4 were included
      in this post-authorization, non-interventional, observational prospective safety
      study, conducted in 8 psychiatric centers in the Czech -Republic. The acute
      treatment phase lasted 5 weeks: 1 week of titration and 4 weeks of full-dose
      treatment. Patients had follow-up visits 9 and 21 weeks after commencing 
      treatment. RESULTS: Overall, 85 patients were enrolled in the study, of which 80
      completed the acute treatment of 5 weeks. There were significant decreases in the
      overall MADRS score from the baseline mean value of 27.4-21.2 at week 1 (p <
      0.001), and a further decrease to 7.9 at week 5 (p < 0.001). The severity of
      depression according to CGI/S gradually declined. Most patients reported
      improvement after 6 days of trazodone treatment. The most frequent adverse drug
      reactions (ADRs) reported were somnolence and fatigue. CONCLUSIONS: Trazodone, in
      the new extended-release formulation, had very good effects in clinical practice,
      both in previously untreated depressive episodes and in episodes not responsive
      to previous antidepressive therapy.

PMID- 30099453
TI  - Multidose Methotrexate Treatment of Ectopic Pregnancies with High initial beta
      Human Chorionic Gonadotropin: Can Success Be Predicted?
AB  - OBJECTIVE: To investigate the clinical results and prognostic factors of multiple
      dose methotrexate (Mtx) treatment of ectopic pregnancy patients with high initial
      serum (human chorionic gonadotropin [hCG]). DESIGN: Retrospective cohort study.
      PATIENTS: Twenty-six ectopic pregnancy patients with serum (betahCG) > 5,000
      mIU/mL who received multiple doses of Mtx (1 mg/kg) with folinic acid rescue on
      the alternating days. RESULTS: Success rate was 88.5%. All failures were tubal
      ruptures in those who underwent surgery. Median initial hCG values of the success
      and the failure patients were 8,582 (5,058-31,114) and 5,280 (5,042-13,563)
      mIU/mL respectively (p > 0.05). Side effects were seen in 18 patients (69.2%, one
      bone marrow suppression and 17 minor side effects). The number of Mtx injections
      (7.04 +/- 1.71), Mtx dose (71.35 +/- 13.16 mg) and follow-up period (42.04 +/-
      23.77 days) did not differ between groups. Body mass index (BMI), Mtx dose,
      number of Mtx and change in betahCG levels between the initials and the levels
      measured 2 days after the 3rd, 4th, and 5th Mtx injections were found to be
      highly predictive for tubal rupture. CONCLUSIONS: Multiple-dose Mtx treatment of
      ectopic pregnancies with high initial hCG is safe and effective. BMI, Mtx dose,
      number of Mtx injections and the decrement of betahCG levels were found as highly
      predictive for the success of the treatment.

PMID- 30099452
TI  - 11beta-Hydroxysteroid Dehydrogenase Type 1 Inhibitor Development by Lentiviral
      Screening Based on Computational Modeling.
AB  - In this study, rat and human 11beta-hydroxysteroid dehydrogenase type 1 (11beta
      HSD1) have been cloned by lentiviral transduction and expressed by CHO-K1 cells.
      The results showed that recombinant plasmids contained R11bhsd1 or H11bhsd1 have
      been constructed, which is consistent with the gene bank respectively. A clone
      cell was selected with G418 and cultivated to express 11beta-HSD1. 11beta-HSD1
      catalytic activity of rat and human were 99.5 and 98.7%, respectively, determined
      by scanning radiometer. And the cloned CHO-K1 cells expressed the protein of
      11beta-HSD1 in a long-term and stable manner, which makes it suitable for
      screening 11beta-HSD1 inhibitor. The three-dimensional structure of 11beta-HSD1
      was used for studying the interaction between inhibitor and enzyme by the binding
      poses predicted by AutoDock and LeDock software. The docking results revealed
      that compound 8 forms 2 hydrogen bonds with the residues of Gly-216 and Ile-218
      in 11beta-HSD1, that is to say compound 8 maybe a good 11beta-HSD1 inhibitor.
      Moreover, C57BL/6 mice with R11bHsd1 overexpression had a higher body weight,
      glucose, total cholesterol, and triglyceride levels compared to the mice treated
      with an empty viral vector. The results might provide a beneficial foundation for
      selecting inhibitors of 11beta-HSD1 or for researching drug candidate mechanisms.

PMID- 30099454
TI  - gamma-Acetylcholine Receptor Mediating Dynamic Changes of Resistance to
      Rocuronium in the Denervated Skeletal Muscle.
AB  - BACKGROUND/AIMS: Denervation resulted in resistance to non-depolarizing muscle
      relaxants (NDMRs), the magnitude of which changed after denervation in the
      skeletal muscle. The aim of this study was to investigate whether changed
      potencies of rocuronium were due to altered gamma-acetylcholine receptor (gamma
      AChR) expression after skeletal muscle denervation. METHODS: Innervated and
      denervated muscle cells were used in this study. Patch clamp and Western blotting
      techniques were separately applied to examine IC50 values of rocuronium and gamma
      AChR protein expression at different times after denervation. Then, using the
      linear Pearson correlation analysis, the relationship between IC50 values of
      rocuronium and gamma-AChR expression was tested. RESULTS: Compared with the
      innervated control, both IC50 values of rocuronium and gamma-AChR expression
      significantly increased at Day 4, 7, and 14 after denervation in the skeletal
      muscle. Furthermore, gamma-AChR protein and IC50 values of rocuronium exibited a
      significant positive correlation (r = 0.7678, p < 0.0001). CONCLUSION: These
      above results indicated that dynamic changes of resistance to NDMRs may be due to
      altered gamma-AChR expression after skeletal muscle denervation.

PMID- 30099455
TI  - Profiles and Bioinformatics Analysis of Differentially Expressed Circrnas in
      Taxol-Resistant Non-Small Cell Lung Cancer Cells.
AB  - BACKGROUND/AIMS: Circular RNAs (circRNAs) act as microRNA (miRNA) sponges that
      regulate gene expression and are involved in physiological and pathological
      processes. In this study, we evaluated the roles of circRNAs in the
      chemoresistance of non-small cell lung cancer (NSCLC) to taxol. METHODS: High
      throughput circRNA microarrays were employed to investigate the circRNA profiles
      of parental A549 and taxol-resistant A549/Taxol cells. We predicted the miRNA
      targets of differentially expressed circRNAs via miRNA prediction software and
      then constructed a circRNA/miRNA network using Cytoscape. Bioinformatics analyses
      were performed to annotate dysregulated circRNAs in detail. RESULTS: We detected
      2909 significantly upregulated and 8372 downregulated circRNAs in A549/Taxol
      cells compared with A549 cells. The circRNA/miRNA network displayed their
      interactions, suggesting that circRNAs exert biological effects by absorbing and
      sequestering miRNA molecules. Computational Gene Ontology and pathway analyses
      were used to determine the biological function and signaling pathways of host
      genes of dysregulated circRNAs and to identify potential molecular mechanisms
      prompting the resistance of NSCLC to taxol. CONCLUSION: This study focusing on
      circRNAs related to taxol resistance provides a basis for clarifying the
      development and progression of drug resistance and for identifying therapeutic
      targets in NSCLC.

PMID- 30099456
TI  - MicroRNA-124 Prevents H2O2-Induced Apoptosis and Oxidative Stress in Human Lens
      Epithelial Cells via Inhibition of the NF-kappaB Signaling Pathway.
AB  - AIM: To investigate the regulation of microRNA-124 -(miRNA-124) on NF-kappaB
      pathway from H2O2-induced apoptosis and oxidative stress in human lens epithelial
      cells (hLEC). METHODS: The MTT (3-[4, 5-dimethylthiazol-2-yl]-2,5 diphenyl
      tetrazolium bromide) assay was used to detect hLEC -viability. HLECs were divided
      into Blank, H2O2, mimics (miRNA-124 mimics) + H2O2, NC+ H2O2, pyrrolidine
      dithiocarbamate (PDTC; NF-kappaB signaling pathway inhibitor) + H2O2, and
      inhibitors (miRNA-124 inhibitors) + PDTC + H2O2 groups. Quantitative real-time
      polymerase chain reaction and Western blot were employed to detect mRNA and
      protein expressions, Dichloro-dihydro-fluorescein diacetate to measure reactive
      oxygen species (ROS) production, and AnnexinV-FITC/PI staining to determine cell
      apoptosis. The mitochondrial membrane potential (MMP) was detected by
      fluorescence probe JC-1. RESULTS: The H2O2-induced hLEC showed reductions in cell
      viability with decreased miRNA-124 but increased p-p65 in a dose-/time-dependent
      manner. Furthermore, ROS production, malondialdehyde content, Bax and Caspase-3
      expressions, and cell apoptosis were elevated in H2O2-induced hLEC, whereas the
      activities of superoxide dismutase and glutathione peroxidase, Bcl-2 expression,
      MMP, as well as the mitochondrial energy metabolism genes were reduced.
      Additionally, miRNA-124 mimics and PDTC both decreased the p-p65 and reversed the
      cytotoxicity in H2O2-induced hLEC. CONCLUSION: MiRNA-124 prevents H2O2-induced
      oxidative stress and apoptosis in hLEC through suppressing the activation of the
      NF-kappaB pathway.

PMID- 30099458
TI  - The Utility of Feticide Procedure to Shorten the Induction-to-Abortion Interval
      in Medical Abortion.
AB  - AIM: To evaluate the effect of intracardiac potassium chloride feticide procedure
      (FP) on the induction-to-abortion (I-to-A) interval for various indications in
      the termination of pregnancy. METHOD: Medically indicated abortions between 17
      and 28 weeks' gestation were retrospectively evaluated and allocated into 2
      groups: Cases with (group 1, n = 58) or without an FP (group 2, n = 60). I-to-A
      intervals were compared across the groups, considering different baseline
      parameters and fetal abnormality categories. RESULTS: There were no differences
      among the groups except in gestational age (GA; mean, 21.2 vs. 19.6 weeks, p =
      0.01) in group 1. Overall, the I-to-A interval was shorter (900 +/- 233 vs. 1,198
      +/- 375 min, p = 0.001) and prolonged medical abortion (I-to-A interval > 48 h)
      was less common (2% vs. 6%, p = 0.03) in group 1. The facilitating effect of FP
      persisted when indications were categorized as central nervous system,
      chromosomal, other structural abnormalities, and unclassified conditions.
      Logistic regression analyses demonstrated the following features to be associated
      with expulsion of fetus after 24-h: (1) advanced GA (> 24 week; aOR 6.9, 95% CI
      3.24-14.72), (2) central nervous system abnormalities (aOR 5.3, 95% CI 2.6-11.4),
      (3) lack of feticide (aOR 3.67, 95% CI 2.24-10.72). CONCLUSION: FPs seem to
      shorten the I-to-A interval and decrease prolonged I-to-A interval rates. This
      facilitating effect remains unchanged for various medical indications.

PMID- 30099459
TI  - Human Paleoneurology and the Evolution of the Parietal Cortex.
AB  - Paleoneurology deals with the study of brain anatomy in fossil species, as
      inferred from the morphology of their endocranial features. When compared with
      other living and extinct hominids, Homo sapiens is characterized by larger
      parietal bones and, according to the paleoneurological evidence, also by larger
      parietal lobes. The dorsal elements of the posterior parietal cortex (superior
      parietal lobules, precuneus, and intraparietal sulcus) may be involved in these
      morphological changes. This parietal expansion was also associated with an
      increase in the corresponding vascular networks, and possibly with increased heat
      loads. Only H. sapiens has a specific early ontogenetic stage in which brain form
      achieves such globular appearance. In adult modern humans, the precuneus displays
      remarkable variation, being largely responsible for the longitudinal parietal
      size. The precuneus is also much more expanded in modern humans than in
      chimpanzees. Parietal expansion is not influenced by brain size in fossil
      hominids or living primates. Therefore, our larger parietal cortex must be
      interpreted as a derived feature. Spatial models suggest that the dorsal and
      anterior areas of the precuneus might be involved in these derived morphological
      variations. These areas are crucial for visuospatial integration, and are
      sensitive to both genetic and environmental influences. This article reviews
      almost 20 years of my collaborations on human parietal lobe evolution,
      integrating functional craniology, paleoneurology, and evolutionary neuroanatomy.

PMID- 30099457
TI  - A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats.
AB  - BACKGROUND: NADPH oxidases (Nox) is a major enzyme system contributing to
      oxidative stress, which plays an important role in the pathogenesis of diabetic
      kidney disease (DKD). We have shown an elevation of renal Nox1, Nox2, and Nox4 in
      diabetic mice. APX-115, a pan-Nox inhibitor, attenuated the progression of DKD in
      mice. As the standard diabetic mice cannot fully mimic human DKD, the present
      study was aimed to show the dose-dependent effect and to provide a confirmatory
      evidence of APX-115 in attenuating DKD in diabetic rats. METHOD: Type 1 diabetes
      was induced by a single 60 mg/kg intraperitoneal injection of streptozotocin in
      Sprague-Dawley rats. 0.5, 5, or 30 mg APX-115/kg/day or losartan 1 mg/kg/day were
      administered orally to diabetic rats for 8 weeks. RESULTS: APX-115 treatment
      showed an improvement in kidney function and tubular and podocyte -injury, as
      well as attenuation of inflammation, fibrosis, and oxidative stress as much as
      losartan, a comparative drug and mainstay treatment in DKD. Therapeutic effect of
      APX-115 was exhibited in a dose-dependent manner; a dose of 30 mg/kg displayed a
      superior efficacy. CONCLUSION: This finding verified the pre-clinical data of APX
      115 in protecting against DKD, which is important to bring APX-115 toward the
      next stage of drug development.

PMID- 30099460
TI  - The Endocranial Cavity of Oviraptorosaur Dinosaurs and the Increasingly Complex,
      Deep History of the Avian Brain.
AB  - Unraveling the origins of the character complexes diagnosing major crown clades
      is one of the greatest challenges in evolutionary biology. These origination
      events tend to optimize along extraordinarily long stem lineages where the
      comparative biology of extant lineages is relatively weak in its heuristic power.
      Here we add to a growing paleontological literature on the evolutionary origins
      of the modern avi an brain by describing the endocranial casts of two
      oviraptorosaur dinosaurs, Citipati osmolskae and Khaan mckennai. These fossil
      data confirm the antiquity of several avian features, including the expanded
      cerebrum. They also extend our appreciation of both the inherent variability in
      the brain-skull relationship along the avian stem and the dynamic nature of these
      crown characters in the earliest history of their expression.

PMID- 30099461
TI  - Comparative Primate Connectomics.
AB  - A connectome is a comprehensive map of neural connections of a species nervous
      system. While recent work has begun comparing connectomes across a wide breadth
      of species, we present here a more detailed and specific comparison of
      connectomes across the primate order. Long-range connections are thought to
      improve communication efficiency and thus brain function but are costly in terms
      of energy and space utilization. Methods for measuring connectivity in the brain
      include measuring white matter volume, histological cell counting, anatomical
      tract tracing, diffusion-weighted imaging and tractography, and functional
      connectivity in MRI. Comparisons of global white matter connectivity suggest that
      larger primate brains are less well connected than smaller primate brains, but
      that humans have more connections than expected for our cortical neuron number,
      which may be concentrated in the prefrontal cortex. Although there is significant
      overlap in structural connectivity between humans and nonhuman primates, human
      specific connections are found in cortical areas involved with language,
      imitation, and tool use. Similar to structural connectivity, there is also
      widespread overlap between humans and macaques in resting state functional
      connectivity. However, there are again a number of human-specific connections in
      cortical regions involved in language, tool use, and empathy. Comparative
      connectomics also offers the opportunity to detect specializations of
      connectivity in other primate species besides humans. Future research should
      capitalize on the ability of diffusion tractography to measure connectivity in
      postmortem brains that could expand the representation of species beyond humans,
      chimpanzees, and rhesus macaques, and facilitate identification of connectivity
      based adaptations to different social and ecological niches. This work will
      require careful attention to establishing cortical homologies across species and
      to improving tractography methods to limit detection of false-positive and false
      negative connections. Finally, it will be important to attempt to establish the
      functional significance of variation in connectivity profiles by examining how
      these covary with behavior and cognition both across and within species.

PMID- 30099462
TI  - Augmenting Trait-Dependent Diversification Estimations with Fossil Evidence: A
      Case Study Using Osmoregulatory Neurovasculature.
AB  - When comparative neuromorphological studies are extended into evolutionary
      contexts, traits of interest are often linked to diversification patterns.
      Features demonstrably associated with increases in diversification rates and the
      infiltration or occupation of novel niche spaces are often termed "key
      innovations." Within the past decade, phylogenetically informed methods have been
      developed to test key innovation hypotheses and evaluate the influence these
      traits have had in shaping modern faunas. This is primarily accomplished by
      estimating state-dependent speciation and extinction rates. These methods have
      important caveats and guidelines related to both calculation and interpretation,
      which are necessary to understand in cases of discrete (qualitative) character
      analysis, as can be common when studying the evolution of neuromorphology. In
      such studies, inclusion of additional characters, acknowledgement of character
      codistribution, and addition of sister clade comparison should be explored to
      ensure model accuracy. Even so, phylogenies provide a survivor-only examination
      of character evolution, and paleontological contexts may be necessary to
      replicate and confirm results. Here, I review these issues in the context of
      selective brain cooling - a neurovascular-mediated osmoregulatory physiology that
      dampens hypothalamic responses to heat stress and reduces evaporative water loss
      in large-bodied mammals. This binary character provides an example of the
      interplay between sample size, evenness, and character codistribution. Moreover,
      it allows for an opportunity to compare phylogenetically constrained results with
      paleontological data, augmenting survivor-only analyses with observable
      extinction patterns. This trait- dependent diversification example indicates that
      selective brain cooling is significantly associated with the generation of modern
      large-mammal faunas. Importantly, paleontological data validate phylogenetic
      patterns and demonstrate how suites of characters worked in concert to establish
      the large-mammal communities of today.

PMID- 30099463
TI  - The Utility of DiceCT Imaging for High-Throughput Comparative Neuroanatomical
      Studies.
AB  - Advancements in imaging techniques have drastically improved our ability to
      visualize, study, and digitally share complex, often minute, anatomical
      relationships. The recent adoption of soft-tissue X-ray imaging techniques, such
      as diffusible iodine-based contrast-enhanced computed tomography (diceCT), is
      beginning to offer previously unattainable insights into the detailed
      configurations of soft- tissue complexes across Metazoa. As a contrast agent,
      dissolved iodine diffuses deeply throughout preserved specimens to bind fats and
      carbohydrates that are natural ly present within metazoan soft tissues,
      increasing the radiodensities of these tissues in predictable ways. Like the
      current "gold standard" of magnetic resonance imaging, diceCT does not require
      physical dissection and can differentiate between the lipid content of myelinated
      versus nonmyelinated tissues, thereby offering great potential for
      neuroanatomical studies. Within the brain, for example, diceCT distinguishes
      myelinated fiber tracts from unmyelinated cortices, nuclei, and ganglia and
      allows three-dimensional visualization of their anatomical interrelationships at
      previously unrealized spatial scales. In this study, we illustrate the utility of
      diceCT for the rapid visualization of both external and internal brain anatomy in
      vertebrates - alongside the intact bones of the skull and the complete,
      undisturbed pathways of peripheral nerves, up to and including the target organs
      that they innervate. We demonstrate the transformative potential of this
      technique for developing high-resolution neuroanatomical datasets and describe
      best practices for imaging large numbers of specimens for broad evolutionary
      studies across vertebrates.

PMID- 30099466
TI  - Title Page/Table of Contents.

PMID- 30099465
TI  - From Fossils to Function: Integrative and Taxonomically Inclusive Approaches to
      Vertebrate Evolutionary Neuroscience.

PMID- 30099464
TI  - Development and Evolution of Cerebral and Cerebellar Cortex.
AB  - Cerebral cortex and cerebellar cortex both vary enormously across species in
      their size and complexity of convolutions. We discuss the development and
      evolution of cortical structures in terms of anatomy and functional organization.
      We propose that the distinctive shapes of cerebral and cerebellar cortex can be
      explained by relatively few developmental processes, notably including mechanical
      tension along axons and dendrites. Regarding functional organization, we show how
      maps of myelin content in cerebral cortex are evolutionarily conserved across
      primates but differ in the proportion of cortex devoted to sensory, cognitive,
      and other functions. We summarize recent progress and challenges in (i)
      parcellating cerebral cortex into a mosaic of distinct areas, (ii) distinguishing
      cortical areas that correspond across species from those that are present in one
      species but not another, and (iii) using this information along with surface
      based interspecies registration to gain deeper insights into cortical evolution.
      We also comment on the methodological challenges imposed by the differences in
      anatomical and functional organization of cerebellar cortex relative to cerebral
      cortex.

PMID- 30099467
TI  - Inhibition of Nicotine Dependence by Curcuminoid Is Associated with Reduced
      Acetylcholinesterase Activity in the Mouse Brain.
AB  - Nicotine is a stimulatory component in tobacco that activates the central nervous
      system reward pathway and causes nicotine dependence. We found that the anti
      inflammatory agent, curcuminoid, prevents nicotine dependence and relapse, as
      assessed by the conditioned placed preference test. Curcuminoid (1, 3.2, and 10
      mg.kg-1, oral) dose-dependently inhibited nicotine dependence and enhanced
      nicotine extinction when administrated 30 min prior to nicotine administration
      (0.5 mg.kg-1, i.p.) for 7 days. In addition, curcuminoid significantly suppressed
      the priming effects of nicotine and inhibited acetylcholinesterase (AChE)
      activity. Taken together, curcuminoid ameliorates nicotine dependence and
      relapse, in part via the inhibition of the AChE activity in the brain.

PMID- 30099468
TI  - Association of Peridialysis Blood Pressure and Its Variability with
      Cardiovascular Events in Hemodialysis Patients.
AB  - BACKGROUND/AIMS: Blood pressure variability (BPV) is a novel cardiovascular risk
      factor for the population undergoing hemodialysis (HD). METHODS: We conducted a
      retrospective cohort study of 526 HD patients. Four short-term peridialysis BPV
      metrics were analyzed: systolic blood pressure (SBP) change, SBP coefficient of
      variation (CV), SBP intradialytic average real variability (ARV), and absolute
      SBP residual. Multi variate analysis with Cox regression models were used to
      account for the potential confounders. RESULTS: Short-term BPV is found to be
      affected by age, pre-dialysis SBP, antihypertensive drugs, dialysis time, and
      vascular access. Calcium-channel blockers (CCBs) were found to be associated with
      lower BPV than those on non-CCB therapy or no antihypertensive drugs. Patients
      dialyzed in the morning had a greater absolute SBP change than those dialyzed in
      the afternoon or evening. Patients using fistulas had a lower BPV than catheters.
      Higher BPV metrics including SBP CV (unadjusted hazard ratio [HR]: 1.37, 95%
      confidence interval [CI] 1.14-1.66, p=0.001), SBP intradialytic ARV (unadjusted
      HR: 1.46, 95% CI: 1.20-1.77, p< 0.001), and SBP residual (unadjusted HR: 1.47,
      95% CI: 1.21-1.79, p< 0.001) were associated with a greater risk of
      cardiovascular events. After complete multivariate adjustment for other potential
      confounders, the HR remained statistically significant for SBP intradialytic ARV
      (HR 1.31, 95% CI: 1.04-1.66, p=0.024). CONCLUSION: Peridialytic BPV may be a
      potential target for improved blood pressure (BP) management in HD patients. Each
      short-term BPV metric has different advantages and disadvantages and should be
      applied according to the clinical context and purpose.

PMID- 30099470
TI  - Care Pathway Effect on In-Hospital Care for ST-Elevation Myocardial Infarction.
AB  - OBJECTIVES: To study the care pathway effect on the percentage of patients with
      ST-elevation myocardial infarction -(STEMI) receiving timely coronary reperfusion
      and the percentage of STEMI patients receiving optimal secondary prevention.
      METHODS: A care pathway was implemented by the Collaborative Model for Achieving
      Breakthrough Improvement. One pre-intervention and 2 post-intervention audits
      included all adult STEMI patients admitted within 24 h after onset and eligible
      for reperfusion. Adjusted (hospital random intercepts and controls for transfer
      and out-of-office admission) differences in composite outcomes were analyzed by a
      multilevel logistic regression. RESULTS: Significant improvements in intervals
      between the first medical contact (FMC) to percutaneous coronary intervention
      (PCI) and between the door to PCI were shown between post-intervention audit II
      and post-intervention audit I. Secondary prevention significantly deteriorated at
      post-intervention audit I but improved significantly between both post
      intervention audits. Six out of nine outcomes were significantly poorer in the
      case of transfer. The interval from FMC to PCI was significantly poorer for
      patients admitted during out-of-office hours. CONCLUSIONS: After care pathway
      implementation, composite outcomes improved for in-hospital STEMI care.
      Collaborative efforts exploited heterogeneity in performance between hospitals.
      Iterative and incremental care pathway implementation maximized performance
      improvement.

PMID- 30099471
TI  - Care Pathways in ST Elevation Myocardial Infarction. Maybe a Modern Way to
      Hippocrates' Oath: "Harm Less and Help More".

PMID- 30099469
TI  - Systematic DNA Study for Fabry Disease in the End Stage Renal Disease Patients
      from a Southern Italy Area.
AB  - BACKGROUND/AIMS: Fabry disease (FD) is a lysosomal storage disorder characterized
      by pervasive renal involvement. However, this disease is underdiagnosed in
      patient with chronic kidney disease (CKD), including those with end stage renal
      disease (ESRD), so their investigation represents an unexploited opportunity for
      early diagnosis of the disease and for its identification in relatives of
      affected patients. METHODS: We investigated Fabry disease in a clinical and
      biological database including ESRD patients of unknown cause in a geographical
      area with 2 million residents. The study was based on state of art GLA gene
      sequencing and was extended to relatives of affected ESRD patients. RESULTS:
      Among ESRD patients qualified for enrollment into this study, a previously
      undiagnosed young man harboring the mutation p.I91T was identified. The study of
      the proband's family led to the identification of 8 additional cases. In another
      ESRD male patient, we identified the functional polymorphism p.D313Y.
      Furthermore, in 55 ESRD patients (24.2%) we found intronic polymorphisms of
      uncertain functional relevance in the non-coding regions of the GLA gene.
      CONCLUSION: A comprehensive survey of ESRD patients in a geographical area of 2
      million residents identified one undiagnosed case of Fabry disease and led to the
      identification of 8 additional cases among his relatives. Screening protocols
      starting from the dialysis population and upstream extended to families of
      affected individuals may be an effective strategy to maximize the early
      identification of subjects with Fabry disease.

PMID- 30099472
TI  - Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms Are Associated with Risk
      of Intervertebral Disc Degeneration in Chinese Han Population: A Case Control
      Study.
AB  - BACKGROUND The present study aimed to evaluate whether the fat mass and obesity
      associated (FTO) gene polymorphisms are associated with risk of intervertebral
      disc degeneration (IDD) in a largest Chinese Han population. MATERIAL AND METHODS
      There were 502 IDD patients and 497 healthy controls enrolled in this study.
      Nineteen single nucleotide polymorphisms (SNPs) in the FTO gene were tested using
      the Sequenom MassARRAY platform. The Hardy-Weinberg equilibrium test, followed by
      allelic, genotypic, haplotypic association, and SNP interaction analyses were
      used for SNP evaluation. The Genotype-Tissue Expression (GTEx) database was used
      to evaluate expression quantitative trait loci (eQTL) value of polymorphism.
      Spearman rank correlation and logistic regression analyses were used for
      assessing the internal relation between genotypic changes and the risk of IDD.
      RESULTS Seventeen SNPs survived the Hardy-Weinberg equilibrium test. Allelic
      analysis showed that allele T of SNP rs1121980 was a risk allele. Haplotypic and
      SNP interaction analyses suggested that 2 haplotypes and 5 SNP combinations were
      associated with the predisposition of IDD respectively. GTEx database revealed
      that the SNP rs1121980 might interfere with the expression of the FTO gene in the
      muscle-skeletal system. Through clinical statistics analysis, the different
      genotypes of rs1121980 can present different disease severity of IDD. CONCLUSIONS
      Our study suggests that rs1121980 can become a biomarker for the screening and
      prognosis of IDD. The 2 haplotype blocks and 5 SNP-SNP combinations that we
      discovered might be indicative of the onset of IDD. Therefore, our study might
      serve as evidence for future IDD molecular diagnosis.

PMID- 30099473
TI  - Evaluation of Sexual Function in Women with Hypogonadotropic Hypogonadism Using
      the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI).
AB  - BACKGROUND Hypogonadotropic hypogonadism (HH), or secondary hypogonadism, results
      from reduced secretion of gonadotropins, including follicle-stimulating hormone
      (FSH) and luteinizing hormone (LH), by the pituitary gland, resulting in lack of
      production of sex steroids. The aim of this study was to evaluate self-reported
      sexual function in sexually active women with and without HH using two evaluation
      methods, the Female Sexual Function Index (FSFI) and the Beck Depression
      Inventory (BDI). MATERIAL AND METHODS The study recruited 88 women who attended
      an outpatient in vitro fertilization (IVF) clinic in Turkey for primary
      infertility, between August 2013 and August 2016. All patients were sexually
      active with an age that ranged from 20-41 years. Following an initial
      examination, including measurement of FSH and LH levels, all study participants
      were asked to complete the FSFI and BDI self-reporting questionnaires. Patients
      were divided into Group 1 (with HH) (N=42) and Group 2 (the control group)
      (N=46). RESULTS Analysis of the patient responses to questions regarding their
      sexual function in the FSFI and BDI showed that of the 42 patients in Group 1
      (the HH group), 27 patients (64.28%) reported sexual dysfunction; of the 46
      patients in Group 2 (the control group) 14 patients (30.34%) reported sexual
      dysfunction. Analysis of the FSFI lubrication scores and orgasm scores showed a
      statistically significant difference between the two groups (both, p<0.01).
      CONCLUSIONS Women with HH require both physical and psychological support to
      improve their sexual function, self-esteem, mental health, and quality of life.

PMID- 30099474
TI  - Validation of rapid 4-component body composition assessment with the use of dual
      energy X-ray absorptiometry and bioelectrical impedance analysis.
AB  - Background: The 4-component (4C) model is a criterion method for human body
      composition that separates the body into fat, water, mineral, and protein, but
      requires 4 measurements with significant cost and time requirements that preclude
      wide clinical use. A simplified model integrating only 2 measurements-dual-energy
      X-ray absorptiometry (DXA) and bioelectrical impedance analysis (BIA)-and 10 min
      of patient time has been proposed. Objective: We aimed to validate a rapid,
      simplified 4C DXA + BIA body composition model in a clinical population. Design:
      This was a cross-sectional observational study of 31 healthy adults. Participants
      underwent whole-body DXA, segmental BIA, air displacement plethysmography (ADP),
      and total body water (TBW) measurement by deuterium (D2O) dilution. 4C
      composition was calculated through the use of the Lohman model [DXA mineral mass,
      D2O TBW, ADP body volume (BV), scale weight] and the simplified model (DXA
      mineral mass and BV, BIA TBW, scale weight). Accuracy of percentage of fat (%Fat)
      and protein measurements was assessed via linear regression. Test-retest
      precision was calculated with the use of duplicate DXA and BIA measurements.
      Results: Of 31 participants, 23 were included in the analysis. TBWBIA showed good
      test-retest precision (%CV = 5.2 raw; 1.1 after outlier removal) and high
      accuracy to TBWD2O [TBWD2O = 0.956*TBWBIA, R2= 0.92, root mean squared error
      (RMSE) = 2.2 kg]. %Fat estimates from DXA, ADP, D2O, and BIA all showed high
      correlation with the Lohman model. However, only the 4C simplified model provides
      high accuracy for both %Fat (R2 = 0.96, RMSE = 2.33) and protein mass (R2= 0.76,
      RMSE = 1.8 kg). %Fat precision from 4C DXA + BIA was comparable with DXA (root
      mean square-SD = 0.8 and 0.6 percentage units, respectively). Conclusions: This
      work validates a simplified 4C method that measures fat, water, mineral, and
      protein in a 10-min clinic visit. This model has broad clinical application to
      monitor many conditions including over/dehydration, malnutrition, obesity,
      sarcopenia, and cachexia.

PMID- 30099475
TI  - Linking HIV and Viral Hepatitis Surveillance Data: Evaluating a Standard,
      Deterministic Matching Algorithm Using Data From 6 US Health Jurisdictions.
AB  - Accurate interpretations and comparisons of record linkage results across
      jurisdictions require valid and reliable matching methods. We compared existing
      matching methods used by 6 US state and local health departments (Houston, Texas;
      Louisiana; Michigan; New York, New York; North Dakota; and Wisconsin) to link
      human immunodeficiency virus and viral hepatitis surveillance data with a 14-key
      automated, hierarchical deterministic matching method. Applicable years of study
      varied by disease and jurisdiction, ranging from 1979 to 2016. We calculated
      percentage agreement and Cohen's kappa coefficient to compare the matching
      methods used within each jurisdiction. We calculated sensitivity, specificity,
      and positive predictive value for each matching method, as compared with a new
      standard that included manual review of discrepant cases. Agreement between the
      existing matching method and the deterministic matching method was 99.6% or
      higher in all jurisdictions; Cohen's kappa values ranged from 0.87 to 0.98. The
      sensitivity of the deterministic matching method ranged from 97.4% to 100% in the
      6 jurisdictions; specificity ranged from 99.7% to 100%; and positive predictive
      value ranged from 97.4% to 100%. Although no gold standard exists, prior
      assessments of existing methods and review of discrepant classifications suggest
      good accuracy and reliability of our deterministic matching method, with the
      advantage that our method reduces the need for manual review and allows for
      standard comparisons across jurisdictions when linking human immunodeficiency
      virus and viral hepatitis data.

PMID- 30099476
TI  - A comparative analysis of cell-type adjustment methods for epigenome-wide
      association studies based on simulated and real data sets.
AB  - Technological advances and reduced costs of high-density methylation arrays have
      led to an increasing number of association studies on the possible relationship
      between human disease and epigenetic variability. DNA samples from peripheral
      blood or other tissue types are analyzed in epigenome-wide association studies
      (EWAS) to detect methylation differences related to a particular phenotype. Since
      information on the cell-type composition of the sample is generally not available
      and methylation profiles are cell-type specific, statistical methods have been
      developed for adjustment of cell-type heterogeneity in EWAS.In this study we
      systematically compared five popular adjustment methods: the factored spectrally
      transformed linear mixed model (FaST-LMM-EWASher), the sparse principal component
      analysis algorithm ReFACTor, surrogate variable analysis (SVA), independent SVA
      (ISVA) and an optimized version of SVA (SmartSVA). We used real data and applied
      a multilayered simulation framework to assess the type I error rate, the
      statistical power and the quality of estimated methylation differences according
      to major study characteristics.While all five adjustment methods improved false
      positive rates compared with unadjusted analyses, FaST-LMM-EWASher resulted in
      the lowest type I error rate at the expense of low statistical power. SVA
      efficiently corrected for cell-type heterogeneity in EWAS up to 200 cases and 200
      controls, but did not control type I error rates in larger studies. Results based
      on real data sets confirmed simulation findings with the strongest control of
      type I error rates by FaST-LMM-EWASher and SmartSVA. Overall, ReFACTor, ISVA and
      SmartSVA showed the best comparable statistical power, quality of estimated
      methylation differences and runtime.

PMID- 30099477
TI  - Alcoholic beverages and cancer: raising the alarm.

PMID- 30099478
TI  - Overall survival and risk of second malignancies with cancer chemotherapy and G
      CSF support.
AB  - Background: The use of supportive granulocyte colony-stimulating factor (G-CSF)
      to reduce the risk of neutropenic complications in high-risk cancer patients is
      consistently recommended by several clinical practice guidelines. However, in a
      previous meta-analysis, G-CSF prophylaxis was associated with an increased risk
      of secondary malignancies while reducing long-term mortality. We present here an
      updated systematic review and meta-analysis. Materials and methods: A systematic
      literature search was carried out to identify randomized controlled trials of
      cancer patients receiving conventional-dose chemotherapy, assigned to primary G
      CSF support or a control group without initial G-CSF, with at least 2 years of
      follow-up. Studies were categorized into one of the four groups, based on the
      chemotherapy regimen and study design. An updated meta-analysis was carried out;
      relative risk (RR) and 95% confidence intervals (CIs) for all-cause mortality and
      secondary malignancies were calculated. Results: Of 2604 articles screened, 14
      eligible studies were identified and combined with studies identified in the
      previous systematic literature searches. The updated meta-analysis included a
      total of 68 studies presenting 71 separate comparisons. Survival was
      significantly improved in patients receiving primary G-CSF support, compared with
      patients without primary G-CSF support (mortality RR=0.92; 95% CI 0.90-0.95; ARD=
      3.3%; 95% CI -4.2--2.4; P < 0.0001). The largest improvement in survival was
      observed with dose-dense chemotherapy regimens with G-CSF support, compared with
      controls receiving no G-CSF support (mortality RR=0.86; 95% CI 0.80-0.92; P <
      0.0001). Patients who received primary G-CSF support experienced a significantly
      higher risk of secondary malignancies, compared with controls (RR=1.85; 95% CI
      1.19-2.88; ARD=0.47; 95% CI 0.21-0.73; P < 0.01). Conclusions: Our findings
      demonstrate that overall survival is improved in patients receiving intensified
      chemotherapy with primary G-CSF support, compared with those receiving standard
      chemotherapy. Primary G-CSF support was also associated with a higher risk of
      developing secondary malignancies, including secondary acute myeloid leukemia and
      myelodysplastic syndrome.

PMID- 30099479
TI  - Time-Series Analysis of Air Pollution and Health Accounting for Covariate
      Dependent Overdispersion.
AB  - Time-series studies are routinely used to estimate associations between adverse
      health outcomes and short-term exposures to ambient air pollutants. Use of the
      Poisson log-linear model with the assumption of constant overdispersion is the
      most common approach, particularly when estimating associations between daily air
      pollution concentrations and aggregated counts of adverse health events
      throughout a geographical region. We examined how the assumption of constant
      overdispersion plays a role in estimation of air pollution effects by comparing
      estimates derived from the standard approach with those estimated from covariate
      dependent Bayesian generalized Poisson and negative binomial models that
      accounted for potential time-varying overdispersion. Through simulation studies,
      we found that while there was negligible bias in effect estimates, the standard
      quasi-Poisson approach can result in a larger standard error when the constant
      overdispersion assumption is violated. This was also observed in a time-series
      study of daily emergency department visits for respiratory diseases and ozone
      concentration in Atlanta, Georgia (1999-2009). Allowing for covariate-dependent
      overdispersion resulted in a reduction in the ozone effect standard error, while
      the ozone-associated relative risk remained robust to different model
      specifications. Our findings suggest that improved characterization of
      overdispersion in time-series modeling can result in more precise health effect
      estimates in studies of short-term environmental exposures.

PMID- 30099480
TI  - Education and Cognitive Aging: Accounting for Selection and Confounding in
      Linkage of Data From the Danish Registry and Survey of Health, Ageing and
      Retirement in Europe.
AB  - Earlier studies report inconsistent associations between education and cognitive
      aging. We assessed the association, accounting for selective dropout due to death
      or dementia, and, in a subsample, accounting for confounding by early-life
      intelligence. Data from the Danish component of the Survey of Health, Ageing and
      Retirement in Europe (n = 3,400) were linked to registry data (education records,
      dementia diagnoses, and mortality) and the Danish Conscription Database (youth
      intelligence measurements for 854 men). Word recall and verbal fluency were
      assessed up to 4 times over 10 years (2004-2013) and combined by averaging the z
      scores. We fitted a joint model linking a time-to-event model for dementia or
      death to a linear mixed-effects model for cognitive change. Rate of cognitive
      decline was slower among people with high education compared with low education
      (beta = 0.112, 95% confidence interval (CI): 0.056, 0.170). Adjusting for youth
      intelligence did not attenuate the association between education and cognitive
      decline (crude beta = 0.136, 95% CI: 0.028, 0.244 vs. adjusted beta = 0.145, 95%
      CI: 0.022, 0.269). The results suggest that higher education may slow cognitive
      decline in later life. In this sample, results changed little when accounting for
      selective attrition and confounding by intelligence.

PMID- 30099481
TI  - Ligand binding and retention in snake gourd seed lectin (SGSL). A
      crystallographic, thermodynamic and molecular dynamics study.
AB  - Snake gourd seed lectin (SGSL) is a non-toxic homolog of type II ribosome
      inactivating proteins (RIPs) which contain a catalytic domain and a lectin
      domain. Isothermal titration calorimetry (ITC) measurements of the interactions
      of the protein with LacNAc, Lac, Gal, Me-alpha-Gal were carried out and the
      crystal structures of the native protein and its complex with Lac were
      determined. The crystal structure of the Me-alpha-Gal complex has already been
      determined. While the crystal structure showed the presence of two-sugar-binding
      sites, one on each of the two domains of the lectin chain, ITC measurements
      indicated the presence of only one binding site. In order to resolve this
      anomaly, molecular dynamics (MD) simulations were carried out on the native
      protein and on its complexes with Me-alpha-Gal and Lac. Simulations were also
      performed on the protein after reducing the inter-chain disulfide bridge between
      the two chains. The crystal structures and the simulations confirmed the
      robustness of the protein structure, irrespective of the presence or absence of
      the disulfide bridge. The simulations indicated that although two sites can bind
      sugar, only the ligand at one site is retained in a dynamic situation. The
      studies thus bring out the subtle relationship between binding and retention of
      the ligand.

PMID- 30099482
TI  - A Genetic Map of Ostrich Z Chromosome and the Role of Inversions in Avian Sex
      Chromosome Evolution.
AB  - Recombination arrest is a necessary step for the evolution of distinct sex
      chromosomes. Structural changes, such as inversions, may represent the
      mechanistic basis for recombination suppression and comparisons of the structural
      organization of chromosomes as given by chromosome-level assemblies offer the
      possibility to infer inversions across species at some detail. In birds,
      deduction of the process of sex chromosome evolution has been hampered by the
      lack of a validated chromosome-level assembly from a representative of one of the
      two basal clades of modern birds, Paleognathae. We therefore developed a high
      density genetic linkage map of the ostrich Z chromosome and used this to correct
      an existing assembly, including correction of a large chimeric superscaffold and
      the order and orientation of other superscaffolds. We identified the
      pseudoautosomal region as a 52 Mb segment (~60% of the Z chromosome) where
      recombination occurred in both sexes. By comparing the order and location of
      genes on the ostrich Z chromosome with that of six bird species from the other
      major clade of birds (Neognathae), and of reptilian outgroup species, 25 Z-linked
      inversions were inferred in the avian lineages. We defined Z chromosome
      organization in an early avian ancestor and identified inversions spanning the
      candidate sex-determining DMRT1 gene in this ancestor, which could potentially
      have triggered the onset of avian sex chromosome evolution. We conclude that
      avian sex chromosome evolution has been characterized by a complex process of
      probably both Z-linked and W-linked inversions (and/or other processes). This
      study illustrates the need for validated chromosome-level assemblies for
      inference of genome evolution.

PMID- 30099484
TI  - Interpretation of differential gene expression results of RNA-seq data: review
      and integration.
AB  - Differential gene expression (DGE) analysis is one of the most common
      applications of RNA-sequencing (RNA-seq) data. This process allows for the
      elucidation of differentially expressed genes across two or more conditions and
      is widely used in many applications of RNA-seq data analysis. Interpretation of
      the DGE results can be nonintuitive and time consuming due to the variety of
      formats based on the tool of choice and the numerous pieces of information
      provided in these results files. Here we reviewed DGE results analysis from a
      functional point of view for various visualizations. We also provide an
      R/Bioconductor package, Visualization of Differential Gene Expression Results
      using R, which generates information-rich visualizations for the interpretation
      of DGE results from three widely used tools, Cuffdiff, DESeq2 and edgeR. The
      implemented functions are also tested on five real-world data sets, consisting of
      one human, one Malus domestica and three Vitis riparia data sets.

PMID- 30099483
TI  - Genome-Wide Association Study Reveals Distinct Genetic Susceptibility of Thyroid
      Nodules From Thyroid Cancer.
AB  - Context: Thyroid nodules are very common, and 7% to 15% of them are diagnosed as
      thyroid cancer. However, the inherited genetic risk factors for thyroid nodules
      and their associations with thyroid cancer remain unknown. Objective: To identify
      the genetic variants associated with susceptibility to thyroid nodules in
      comparison with thyroid cancer. Design and Setting: We performed a three-stage
      genome-wide association study for thyroid nodules. The discovery stage involved a
      genome-wide scan of 811 subjects with thyroid nodules and 691 subjects with a
      normal thyroid from a population-based cohort. Replication studies were conducted
      in an additional 1981 cases and 3100 controls from the participants of a health
      checkup. We also performed expression quantitative trait loci analysis of public
      data. Results: The most robust association was observed in TRPM3 (rs4745021) in
      the joint analysis (OR, 1.26; P = 6.12 * 10-8) and meta-analysis (OR, 1.28; P =
      2.11 * 10-8). Signals at MBIP/NKX2-1 were replicated but did not reach genome
      wide significance in the joint analysis (rs2415317, P = 4.62 * 10-5; rs944289, P
      = 8.68 * 10-5). The expression quantitative trait loci analysis showed that TRPM3
      expression was associated with the rs4745021 genotype in thyroid tissues.
      Conclusions: To the best of our knowledge, we have performed the first genome
      wide association study of thyroid nodules and identified a susceptibility locus
      associated with thyroid nodules, suggesting that thyroid nodules have a genetic
      predisposition distinct from that of thyroid cancer.

PMID- 30099485
TI  - Recent advances and prospects of computational methods for metabolite
      identification: a review with emphasis on machine learning approaches.
AB  - MOTIVATION: Metabolomics involves studies of a great number of metabolites, which
      are small molecules present in biological systems. They play a lot of important
      functions such as energy transport, signaling, building block of cells and
      inhibition/catalysis. Understanding biochemical characteristics of the
      metabolites is an essential and significant part of metabolomics to enlarge the
      knowledge of biological systems. It is also the key to the development of many
      applications and areas such as biotechnology, biomedicine or pharmaceuticals.
      However, the identification of the metabolites remains a challenging task in
      metabolomics with a huge number of potentially interesting but unknown
      metabolites. The standard method for identifying metabolites is based on the mass
      spectrometry (MS) preceded by a separation technique. Over many decades, many
      techniques with different approaches have been proposed for MS-based metabolite
      identification task, which can be divided into the following four groups: mass
      spectra database, in silico fragmentation, fragmentation tree and machine
      learning. In this review paper, we thoroughly survey currently available tools
      for metabolite identification with the focus on in silico fragmentation, and
      machine learning-based approaches. We also give an intensive discussion on
      advanced machine learning methods, which can lead to further improvement on this
      task.

PMID- 30099486
TI  - European external quality assessments for identification, molecular typing and
      characterization of Staphylococcus aureus.
AB  - Objectives: We present the results of two European external quality assessments
      (EQAs) conducted in 2014 and 2016 under the auspices of the Study Group on
      Staphylococci and Staphylococcal Infections of ESCMID. The objective was to
      assess the performance of participating centres in characterizing Staphylococcus
      aureus using their standard in-house phenotypic and genotypic protocols. Methods:
      A total of 11 well-characterized blindly coded S. aureus (n = 9), Staphylococcus
      argenteus (n = 1) and Staphylococcus capitis (n = 1) strains were distributed to
      participants for analysis. Species identification, MIC determination,
      antimicrobial susceptibility testing, antimicrobial resistance and toxin gene
      detection and molecular typing including spa typing, SCCmec typing and MLST were
      performed. Results: Thirteen laboratories from 12 European countries participated
      in one EQA or both EQAs. Despite considerable diversity in the methods employed,
      good concordance (90%-100%) with expected results was obtained. Discrepancies
      were observed for: (i) identification of the S. argenteus strain; (ii) phenotypic
      detection of low-level resistance to oxacillin in the mecC-positive strain; (iii)
      phenotypic detection of the inducible MLSB strain; and (iv) WGS-based detection
      of some resistance and toxin genes. Conclusions: Overall, good concordance (90%
      100%) with expected results was observed. In some instances, the accurate
      detection of resistance and toxin genes from WGS data proved problematic,
      highlighting the need for validated and internationally agreed-on bioinformatics
      pipelines before such techniques are implemented routinely by microbiology
      laboratories. We strongly recommend all national reference laboratories and
      laboratories acting as referral centres to participate in such EQA initiatives.

PMID- 30099487
TI  - The 1918-1919 Influenza Pandemic in Portugal: A Regional Analysis of Death
      Impact.
AB  - Although the impact of deaths occurring during the 1918-1919 influenza pandemic
      has been assessed in many archeo-epidemiologic studies, detailed estimates are
      not available for Portugal. We applied negative binomial models to monthly data
      on respiratory-related and all-cause deaths at the national and district levels
      from Portugal for 1916-1922. Influenza-related excess mortality was computed as
      the difference between observed and expected deaths. Poisson regression was used
      to estimate the association of geographic and sociodemographic factors with
      excess mortality. Two waves of pandemic influenza-July 1918 to January 1919 and
      April to May 1919-were identified, for which the excess all-cause death rate was
      195.7 per 10,000 persons. All districts of Portugal were affected. The pandemic
      hit earlier in southeastern districts and the main cities, but excess mortality
      was highest in the northeast, in line with the high death burden experienced by
      northern Spanish provinces. During the period of intense excess mortality
      (fall/winter 1918-1919), population density was negatively associated with
      pandemic impact. This pattern changed during the March 1919 to June 1920 wave,
      when excess mortality increased with population density and in northern and
      western directions. Portuguese islands were less and later affected. Given the
      geographic heterogeneity evidenced in our study, subnational sociodemographic
      characteristics and connectivity should be integrated in pandemic preparedness
      plans.

PMID- 30099489
TI  - Immunotherapy With Apitopes Blocks the Immune Response to TSH Receptor in HLA-DR
      Transgenic Mice.
AB  - We have combined major histocompatibility complex-binding assays with
      immunization and tolerance induction experiments in HLA-DR3 transgenic mice to
      design apitopes (antigen-processing independent epitopes) derived from
      thyrotropin receptor (TSHR) for treatment of patients with Graves' disease (GD).
      A challenge model was created by using an adenovirus-expressing part of the
      extracellular domain of the thyrotropin receptor (TSHR289). This model was used
      to test whether current drug treatments for GD would have an impact on effective
      antigen-specific immunotherapy using the apitope approach. Furthermore, selected
      peptides were assessed for their antigenicity using peripheral blood mononuclear
      cell samples from patients with GD. A mixture of two immunodominant apitopes was
      sufficient to suppress both the T-cell and antibody response to TSHR when
      administered in soluble form to HLA-DR transgenic mice. Tolerance induction was
      not disrupted by current drug treatments. These results demonstrate that antigen
      specific immunotherapy with apitopes from TSHR is a suitable approach for
      treatment of GD.

PMID- 30099488
TI  - Live-Birth Bias and Observed Associations Between Air Pollution and Autism.
AB  - A recent analysis found that exposure to air pollution during specific weeks of
      pregnancy was negatively associated with risk of autism spectrum disorder (ASD)
      when mutually adjusted for postnatal air-pollution exposure. In this commentary,
      we describe 2 possible selection-bias processes that might lead to such results,
      both related to live-birth bias (i.e., the inevitable restriction of the analyzed
      sample to live births). The first mechanism is described using a directed acyclic
      graph and relates to the chance of live birth being a common consequence of both
      exposure to air pollution and another risk factor of ASD. The second mechanism
      involves preferential depletion of fetuses susceptible to ASD in the higher air
      pollution exposure group. We further discuss the assumptions underlying these
      processes and their causal structures, their plausibility, and other studies
      where similar phenomena might have occurred.

PMID- 30099490
TI  - Effectiveness of ceftazidime/avibactam as salvage therapy for treatment of
      infections due to OXA-48 carbapenemase-producing Enterobacteriaceae.
AB  - Background: Experience in real clinical practice with ceftazidime/avibactam is
      limited, and there are even fewer data on infections due to OXA-48-producing
      Enterobacteriaceae. Methods: We designed an observational study of a
      prospectively collected cohort of adult patients receiving ceftazidime/avibactam
      in our centre. Only the first treatment course of each patient was analysed.
      Efficacy and safety were evaluated as 14 and 30 day mortality, recurrence rate at
      90 days, resistance development and occurrence of adverse effects. Results: Fifty
      seven patients were treated with ceftazidime/avibactam. The median age was 64
      years (range 26-86), 77% were male and the median Charlson index was 3. The most
      frequent sources of infection were intra-abdominal (28%), followed by respiratory
      (26%) and urinary (25%). Thirty-one (54%) patients had a severe infection
      (defined as presence of sepsis or septic shock). Most patients received
      ceftazidime/avibactam as monotherapy (81%) and the median duration of treatment
      was 13 days. Mortality at 14 days was 14%. In multivariate analysis, the only
      mortality risk factor was INCREMENT-CPE score >7 (HR 11.7, 95% CI 4.2-20.6).
      There was no association between mortality and monotherapy with
      ceftazidime/avibactam. The recurrence rate at 90 days was 10%.
      Ceftazidime/avibactam resistance was not detected in any case and only two
      patients developed adverse events related to treatment. Conclusions:
      Ceftazidime/avibactam shows promising results, even in monotherapy, for the
      treatment of patients with severe infections due to OXA-48-producing
      Enterobacteriaceae and limited therapeutic options. The emergence of resistance
      to ceftazidime/avibactam was not observed.

PMID- 30099491
TI  - Experience With High-Volume Buttock Fat Transfer: A Report of 137 Cases.
AB  - Background: Buttock augmentation with fat transfer has become increasingly
      popular, with many patients seek high-volume augmentations. There is a lack of
      consensus as to the safe upper-limit of fat that can be transferred. Concern for
      risks such as fat necrosis and fat embolism may lead surgeons to limit the amount
      of fat to place. However, it is unclear if volume alone is associated with these
      complications. The authors examined their experience to evaluate the outcomes of
      high-volume fat transfer. Objective: To evaluate the safety and efficacy of high
      volume buttock fat transfer. Methods: A retrospective case review of all buttock
      fat transfers performed between 2014 and 2016 involving placement of 1000 mL or
      more per buttock was undertaken. Patients were followed clinically and evaluated
      for their subjective assessment of satisfaction. Results: A total of 137 patients
      were identified. A mean of 1331 mL of fat was placed in each buttock (range, 1000
      1890 mL) and the mean age was 35.3 years (range, 19-56 years). One hundred
      eighteen patients (86.1%) were satisfied with their result. None complained of
      the buttocks having been made too large. Nineteen patients (13.9%) wanted the
      buttocks made larger. Eight patients underwent an additional fat transfer
      procedure. Twelve patients (8.8%) had minor cosmetic issues following surgery.
      Another 10 patients (7.3%) had minor medical complications. No patient suffered
      major complications such as fat embolism, venous thromboembolism, infection or
      skin loss. Conclusion: High-volume buttock fat transfer is safe and effective in
      increasing the buttock volume. Complication rates appear to be low with careful
      surgical technique. No serious complications were noted in this case series.

PMID- 30099493
TI  - Corrigendum to Abundance and Diversity in the Melolonthidae Community in
      Cultivated and Natural Grassland Areas of the Brazilian Pampa.

PMID- 30099494
TI  - Letter to the Editor.

PMID- 30099495
TI  - Crohn's Disease-Like Ileitis and the Inhibitory Effect of Sucralose on
      Streptococci.

PMID- 30099496
TI  - Artificial oocyte activation with SrCl2 or calcimycin after ICSI improves
      clinical and embryological outcomes compared with ICSI alone: results of a
      randomized clinical trial.
AB  - STUDY QUESTION: Are pregnancy and birth rates affected by artificial oocyte
      activation (AOA) with SrCl2 or calcimycin after ICSI for couples with male-factor
      infertility linked to abnormal sperm morphology or for couples with previous ICSI
      cycles of unexplained low fertilization or inadequate fertilization associated
      with impaired oocyte morphology? SUMMARY ANSWER: AOA with either SrCl2 or
      calcimycin can improve the rates of clinical pregnancy, ongoing pregnancy and
      live birth compared with ICSI alone, and the two agents have diverse effects for
      different subgroups of patients. WHAT IS KNOWN ALREADY: ICSI is a successful
      treatment for infertility, but not in all individuals. AOA has potential to
      overcome inadequate fertilization in ICSI. Calcimycin and SrCl2 are candidate
      agents for AOA, but their effectiveness remains to be compared. STUDY DESIGN,
      SIZE, DURATION: This study was a randomized, open-label, three-arm, parallel
      group, double-centre, superiority trial conducted between April 2015 and January
      2016. The study evaluated the effects of AOA with calcimycin or SrCl2 for
      clinical pregnancy rates after ICSI and included 343 couples divided into three
      groups. PARTICIPANTS/MATERIALS, SETTING, METHODS: Couples were included if they
      had two previous ICSI cycles of no or low fertilization (0-30%) with unknown
      causes or impaired oocyte morphology. Male-factor infertility cycles (frozen
      thawed sperm, surgically retrieved sperm or ejaculates contained <10 millions
      spermatozoa/ml) undergoing their first ICSI attempt were also included if they
      had 100% abnormal sperm morphology (including globozoospermia and tapered-head).
      Couples were randomized to undergo ICSI with SrCl2 AOA, ICSI with calcimycin AOA
      or ICSI alone, with clinical pregnancy as the primary endpoint. Effect sizes were
      summarized as absolute rate differences (ARDs) and odds ratios (ORs), with
      precision evaluated by 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: Both SrCl2
      and calcimycin AOA improved clinical pregnancy rates compared to ICSI alone (49,
      42 and 27%; ARD 22, 95% CI: 9-33; P = 0.0007 and ARD 16, 95% CI: 3-27; P =
      0.014). SrCl2 and calcimycin AOA were also superior to ICSI alone on the rates of
      ongoing pregnancy (42, 36 and 23%; P = 0.0019 and P = 0.023) and live birth (40,
      33 and 18%; P = 0.0002 and P = 0.012). Among couples with previous ICSI cycles of
      low fertilization, AOA with SrCl2 (but not with calcimycin) was superior to ICSI
      alone for rates of clinical pregnancy (ARD 35 percentage points (pp), P =
      0.0007), ongoing pregnancy (ARD 27 pp, P = 0.009) and live birth (ARD 37 pp, P =
      0.002). Among couples affected by male-factor infertility, AOA with calcimycin
      (but not with SrCl2) was superior to ICSI alone for rates of clinical pregnancy
      (ARD 22 pp, P = 0.006), ongoing pregnancy (ARD 19 pp, P = 0.013) and live birth
      (ARD 17 pp, P = 0.02). LIMITATIONS, REASONS FOR CAUTION: This study was an open
      label trial, and this design might have introduced bias, although randomization
      methods were used. The study did not include a longitudinal follow-up, so further
      evidence is required to demonstrate the safety of AOA. WIDER IMPLICATIONS OF THE
      FINDINGS: The decision to use SrCl2 or calcimycin for AOA after ICSI may depend
      on whether the activation failure originates in the oocyte or the sperm. STUDY
      FUNDING/COMPETING INTEREST(S): The study received no funding and the authors have
      no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: NCT02424214.
      TRIAL REGISTRATION DATE: 22 April 2015. DATE OF FIRST PATIENT'S ENROLMENT: 27
      April 2015.

PMID- 30099492
TI  - The diversity and evolution of pollination systems in large plant clades:
      Apocynaceae as a case study.
AB  - Background and Aims: Large clades of angiosperms are often characterized by
      diverse interactions with pollinators, but how these pollination systems are
      structured phylogenetically and biogeographically is still uncertain for most
      families. Apocynaceae is a clade of >5300 species with a worldwide distribution.
      A database representing >10 % of species in the family was used to explore the
      diversity of pollinators and evolutionary shifts in pollination systems across
      major clades and regions. Methods: The database was compiled from published and
      unpublished reports. Plants were categorized into broad pollination systems and
      then subdivided to include bimodal systems. These were mapped against the five
      major divisions of the family, and against the smaller clades. Finally,
      pollination systems were mapped onto a phylogenetic reconstruction that included
      those species for which sequence data are available, and transition rates between
      pollination systems were calculated.  Key Results : Most Apocynaceae are insect
      pollinated with few records of bird pollination. Almost three-quarters of species
      are pollinated by a single higher taxon (e.g. flies or moths); 7 % have bimodal
      pollination systems, whilst the remaining approx. 20 % are insect generalists.
      The less phenotypically specialized flowers of the Rauvolfioids are pollinated by
      a more restricted set of pollinators than are more complex flowers within the
      Apocynoids + Periplocoideae + Secamonoideae + Asclepiadoideae (APSA) clade.
      Certain combinations of bimodal pollination systems are more common than others.
      Some pollination systems are missing from particular regions, whilst others are
      over-represented. Conclusions: Within Apocynaceae, interactions with pollinators
      are highly structured both phylogenetically and biogeographically. Variation in
      transition rates between pollination systems suggest constraints on their
      evolution, whereas regional differences point to environmental effects such as
      filtering of certain pollinators from habitats. This is the most extensive
      analysis of its type so far attempted and gives important insights into the
      diversity and evolution of pollination systems in large clades.

PMID- 30099497
TI  - Heterogeneity of EGFR-mutant clones and PD-L1 highly expressing clones affects
      treatment efficacy of EGFR-TKI and PD-1 inhibitor.

PMID- 30099498
TI  - Spatio-temporal Virus Surveillance for Severe Acute Respiratory Infections in
      Resource-limited Settings: How Deep Need We Go?

PMID- 30099500
TI  - Reproductive Diapause in North American Populations of the Introduced Lady Beetle
      Hippodamia variegata (Coleoptera: Coccinellidae).
AB  - The Palearctic lady beetle species, Hippodamia variegata (Coleoptera:
      Coccinellidae), first collected in 1984 near Montreal, Quebec, Canada, is
      expanding its distribution into northeastern and north central portions of North
      America. Examination of responses to abiotic factors that influence the seasonal
      biology of H. variegata may provide insights into its potential range expansion
      in North America. The induction and duration of adult hibernal diapause in three
      North American populations of H. variegata, collected between 40 degrees N and 44
      degrees N latitude, was determined at four constant photoperiods (L:D 16:8,
      14:10, 12:12, and 10:14) at 22 degrees C. Thirteen to twenty-one percent of
      females reared at L:D 16:8 entered diapause, whereas shorter photoperiods (L:D
      12:12 and 10:14) induced diapause in 100% of females. Variation in the response
      to L:D 14:10 was observed among the three populations, 27-100% of females
      exhibited reproductive diapause. Pupae and young adults were sensitive to changes
      in constant photoperiods (L:D 16:8 ? 10:14). Individuals reared at L:D 10:14 that
      were moved to L:D 16:8 on the day of pupation or the day of adult eclosion
      produced ovipositing females. Individuals reared at L:D 16:8 and transferred to
      L:D 10:14 on the day of pupation or the day of adult eclosion produced females
      that did not oviposit within 30 d of eclosion.

PMID- 30099499
TI  - A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single
      Genome Sequences.
AB  - Overlapping genes in viruses maximize the coding capacity of their genomes and
      allow the generation of new genes without major increases in genome size. Despite
      their importance, the evolution and function of overlapping genes are often not
      well understood, in part due to difficulties in their detection. In addition,
      most bioinformatic approaches for the detection of overlapping genes require the
      comparison of multiple genome sequences that may not be available in metagenomic
      surveys of virus biodiversity. We introduce a simple new method for identifying
      candidate functional overlapping genes using single virus genome sequences. Our
      method uses randomization tests to estimate the expected length of open reading
      frames and then identifies overlapping open reading frames that significantly
      exceed this length and are thus predicted to be functional. We applied this
      method to 2548 reference RNA virus genomes and find that it has both high
      sensitivity and low false discovery for genes that overlap by at least 50
      nucleotides. Notably, this analysis provided evidence for 29 previously
      undiscovered functional overlapping genes, some of which are coded in the
      antisense direction suggesting there are limitations in our current understanding
      of RNA virus replication.

PMID- 30099501
TI  - Reply to Steigbigel.

PMID- 30099502
TI  - TILLER ANGLE CONTROL 1 modulates plant architecture in response to photosynthetic
      signals.
AB  - Light serves as an important environmental cue in regulating plant architecture.
      Previous work had demonstrated that both photoreceptor-mediated signaling and
      photosynthesis play a role in determining the orientation of plant organs. TILLER
      ANGLE CONTROL 1 (TAC1) was recently shown to function in setting the orientation
      of lateral branches in diverse plant species, but the degree to which it plays a
      role in light-mediated phenotypes is unknown. Here, we demonstrated that TAC1
      expression was light dependent, as expression was lost under continuous dark or
      far-red growth conditions, but did not drop to these low levels during a diurnal
      time course. Loss of TAC1 in the dark was gradual, and experiments with
      photoreceptor mutants indicated this was not dependent upon red/far-red or blue
      light signaling, but partially required the signaling integrator CONSTITUTIVE
      PHOTOMORPHOGENESIS 1 (COP1). Overexpression of TAC1 partially prevented the
      narrowing of branch angles in the dark or under far-red light. Treatment with the
      carotenoid biosynthesis inhibitor norflurazon or the PSII inhibitor 3-(3,4
      dichlorophenyl)-1,1-dimethylurea (DCMU) led to loss of TAC1 expression similar to
      dark or far-red conditions, but expression increased in response to the PSI
      inhibitor paraquat. Treatment of adult plants with norflurazon resulted in upward
      growth angle of branch tips. Our results indicate that TAC1 plays an important
      role in modulating plant architecture in response to photosynthetic signals.

PMID- 30099504
TI  - Do health assets have a protective effect for hospitalized frail older adults?
AB  - Background: Although increasing frailty is predictive of increased mortality and
      length of stay for hospitalized older adults, this approach ignores health assets
      that individuals can utilize to recover following hospital admission. Aim: To
      examine whether health assets mitigate the effect of frailty on outcomes for
      older adults admitted to hospital. Design: Patients of 1418 aged >= 70 years
      admitted to 11 hospitals in Australia were evaluated at admission using the
      interRAI assessment system for Acute Care, which surveys a large number of
      domains, including cognition, communication, mood and behaviour, activities of
      daily living, continence, nutrition, skin condition, falls and medical diagnosis.
      Methods: The data set was interrogated for potential health assets and a multiple
      logistic regression adjusted for frailty index, age and gender as covariates was
      performed for the outcomes mortality, length of stay, re-admission and new need
      for residential care. Results: Inpatient mortality was 3% and 4.5% of patients
      died within 28 days of discharge. Median length of stay was 7 days (IQR 4-11). In
      multivariate analysis that includes frailty, being able to walk further [OR 0.08
      (0.01-0.63)], ability to leave the house [OR 0.35 (0.17-0.74)] and living alone
      [OR 0.28 (0.10-0.79)] were protective against mortality. The presence of a
      support person was associated with a decreased length of stay [OR 0.14 (0.08
      0.25)]. Conclusion: The inclusion of health assets in predictive models can
      improve prognostication and highlights potential interventions to improve
      outcomes for hospitalized older adults.

PMID- 30099503
TI  - Mediator Kinase Disruption in MED12-Mutant Uterine Fibroids From Hispanic Women
      of South Texas.
AB  - Context: Mutations in the gene encoding Mediator complex subunit MED12 are
      dominant drivers of uterine fibroids (UFs) in women of diverse racial and ethnic
      origins. Previously, we showed that UF-linked mutations in MED12 disrupt its
      ability to activate cyclin C-CDK8/19 in Mediator. However, validation of Mediator
      kinase disruption in the clinically relevant setting of MED12-mutant UFs is
      currently lacking. Objective: The objective of this study was twofold. First, to
      extend the ethnic distribution profile of MED12 mutations by establishing their
      frequency in UFs from Hispanic women of South Texas. Second, to examine the
      impact of MED12 mutations on Mediator kinase activity in patient-derived UFs.
      Methods: We screened 219 UFs from 76 women, including 170 tumors from 57 Hispanic
      patients, for MED12 exon 2 mutations, and further examined CDK8/19 activity in
      Mediator complexes immunoprecipitated from MED12 mutation-negative and MED12
      mutation-positive UFs. Results: MED12 exon 2 mutations in UFs from Hispanic women
      are somatic in nature, predominantly monoallelic, and occur at high frequency
      (54.1%). We identified a minimal cyclin C-CDK8 activation domain on MED12
      spanning amino acids 15 through 80 that includes all recorded UF-linked mutations
      in MED12, suggesting that disruption of Mediator kinase activity is a principal
      biochemical defect arising from these pathogenic alterations. Analysis of
      Mediator complexes recovered from patient UFs confirmed this, revealing that
      Mediator kinase activity is selectively impaired in MED12-mutant UFs.
      Conclusions: MED12 mutations are important drivers of UF formation in Hispanic
      women of South Texas. MED12 mutations disrupt Mediator kinase activity,
      implicating altered CDK8/19 function in UF pathogenesis.

PMID- 30099507
TI  - Recanalization of Acute Common Carotid Artery Occlusion: 2-Dimensional Operative
      Video.
AB  - While revascularization of the acutely or chronically occluded internal carotid
      artery has become commonplace with modern endovascular techniques,
      revascularization of an acutely occluded common carotid artery (CCA) is a
      controversial procedure with unique challenges. These challenges can be related
      to the lack of observable markers for identifying vessels during navigation or
      for identifying the exact location and extent of occlusion within the CCA, in
      addition to wide-ranging treatment risks. In this video, we illustrate the
      controversial revascularization of a 68-yr-old woman with an acute CCA occlusion
      who presented with fluctuating neurological symptoms. We believed treatment to be
      indicated by the lack of adequate collaterals on the intracranial CTA, and
      fluctuating symptoms in the absence of an intracranial major vessel occlusion,
      suggesting that the CCA occlusion was exerting important hemodynamic effects and
      at risk of causing a major stroke without revascularization, despite a low
      initial NIH stroke score. Though acute recanalization of patients with low NIH
      stroke score with stent-angioplasty is a controversial procedure, we believed it
      to be necessary in the case of our patient and believe it will likely be the
      focus of the next wave of large clinical trials dedicated to acute stroke.

PMID- 30099508
TI  - Is Splenda, or Sucralose, Causally Linked to Inflammatory Bowel Disease?

PMID- 30099505
TI  - Measurement of Vaccine Direct Effects Under the Test-Negative Design.
AB  - Test-negative designs are commonplace in assessments of influenza vaccination
      effectiveness, estimating this value from the exposure odds ratio of vaccination
      among individuals treated for acute respiratory illness who test positive for
      influenza virus infection. This approach is widely believed to recover the
      vaccine direct effect by correcting for differential health-care-seeking behavior
      among vaccinated and unvaccinated persons. However, the relationship of the
      measured odds ratio to true vaccine effectiveness is poorly understood. We
      derived the odds ratio under circumstances of real-world test-negative studies.
      The odds ratio recovers the vaccine direct effect when 2 conditions are met: 1)
      Individuals' vaccination decisions are uncorrelated with exposure or
      susceptibility to the test-positive or test-negative conditions, and 2)
      vaccination confers "all-or-nothing" protection (whereby certain individuals have
      no protection while others are perfectly protected). Biased effect-size estimates
      arise if either condition is unmet. Such bias might suggest misleading
      associations of vaccine effectiveness with time since vaccination or the force of
      infection of influenza. The test-negative design could also fail to correct for
      differential health-care-seeking behavior among vaccinated and unvaccinated
      persons without stringent criteria for enrollment and testing. Our findings
      demonstrate a need to reassess how data from test-negative studies can inform
      policy decisions.

PMID- 30099506
TI  - Adipose Tissue Transferrin and Insulin Resistance.
AB  - Context: Excessive body iron stores are a risk factor for decreased insulin
      sensitivity (SI) and diabetes. We hypothesized that transcriptional dysregulation
      of genes involved in iron metabolism in adipocytes causes insulin resistance.
      Objective and Design: To define the genetic regulation of iron metabolism and its
      role in SI, we used gene expression, genotype, and SI data from an African
      American cohort (N = 256). Replication studies were performed in independent
      European ancestry cohorts. In vitro studies in human adipocytes were performed to
      define the role of a selected gene in causing insulin resistance. Results: Among
      62 transcripts representing iron homeostasis genes, expression of 30 in adipose
      tissue were correlated with SI. Transferrin (TF) and ferritin heavy polypeptide
      were most positively and negatively associated with SI, respectively. These
      observations were replicated in two independent European ancestry adipose data
      sets. The strongest cis-regulatory variant for TF expression (rs6785596; P = 7.84
      * 10-18) was identified in adipose but not muscle or liver tissue. Variants
      significantly affected the normal relationship of serum ferritin to insulin
      resistance. Knockdown of TF in differentiated Simpson-Golabi-Behmel syndrome
      adipocytes by short hairpin RNA decreased intracellular iron, reduced maximal
      insulin-stimulated glucose uptake, and reduced Akt phosphorylation. Knockdown of
      TF caused differential expression of 465 genes, including genes involved in
      glucose transport, mitochondrial function, Wnt-pathway/ SI, chemokine activity,
      and obesity. Iron chelation recapitulated key changes in the expression profile
      induced by TF knockdown. Conclusion: Genetic regulation of TF expression in
      adipose tissue plays a novel role in regulating SI.

PMID- 30099509
TI  - New Methylation Biomarker Panel for Early Diagnosis of Dysplasia or Cancer in
      High-Risk Inflammatory Bowel Disease Patients.
AB  - Background: The risk of developing colorectal cancer (CRC) is increased in
      patients with inflammatory bowel disease (IBD) of the colon. The aim of the study
      was to evaluate the effectiveness of selected methylation gene panel for the
      early detection of CRC in high-risk IBD patients. Methods: In a discovery phase,
      73 biopsies of 48 IBD patients (associated or not to CRC) were analyzed from
      genome-wide DNA methylation analysis using the Illumina Human Methylation 450K
      BeadChip. The panel of 5 genes selected (EYA4, SLIT2, FLI1, USP44, and SND1) was
      validated prospectively using methylation-specific melting curve analysis in
      biopsies of diseased and adjacent healthy tissue of 203 patients: 38 with IBD and
      associated neoplasia, 81 patients with IBD (25 of them with high risk), 48 with
      sporadic CRC, and 36 healthy controls. Results: The prevalence of methylation was
      higher in patients with IBD and associated neoplasia (both in diseased and
      adjacent healthy tissue, 71% and 52%, respectively) than in healthy controls
      (2/36, 6%; P = 6.72E-05). Methylation in IBD patients at high risk of dysplasia
      or cancer was more frequently detected than in patients at low risk (92% vs 57%;
      odds ratio, 8.63; P = 0.001). EYA4 and SLIT2 were the markers most frequently
      methylated. Differences in methylation levels were more evident in healthy mucosa
      (82% vs 15% high vs low risk, respectively; P = 1.25E-05). Conclusions: Analysis
      of this panel of methylation markers may help in the early identification of
      colorectal dysplasia or cancer in high-risk IBD patients.

PMID- 30099510
TI  - Precision surveillance for viral respiratory pathogens: virome capture sequencing
      for the detection and genomic characterization of severe acute respiratory
      infection in Uganda.
AB  - Background: Precision public health is a novel set of methods to target disease
      prevention and mitigation interventions to high-risk subpopulations. We applied a
      precision public health strategy to syndromic surveillance for severe acute
      respiratory infection (SARI) in Uganda by combining spatiotemporal analytics with
      genomic sequencing to detect and characterize viral respiratory pathogens with
      epidemic potential. Methods: Using a national surveillance network we identified
      patients with unexplained, influenza-negative SARI from 2010-2015. Spatiotemporal
      analyses were performed retrospectively to identify clusters of unexplained SARI.
      Within clusters, respiratory viruses were detected and characterized in naso- and
      oro-pharyngeal swab samples using a novel oligonucleotide probe capture
      (VirCapSeq-VERT) and high-throughput sequencing platform. Linkage to conventional
      epidemiologic strategies further characterized transmission dynamics of
      identified pathogens. Results: Among 2,901 unexplained SARI cases, 9 clusters
      were detected, accounting for 301 (10.4%) cases. Clusters were more likely to
      occur in urban areas and during biannual rainy seasons. Within detected clusters,
      we identified an unrecognized outbreak of measles-associated SARI; sequence
      analysis implicated co-circulation of endemic genotype B3 and genotype D4 likely
      imported from England. We also detected a likely nosocomial SARI cluster
      associated with a novel picobirnavirus most closely related to swine and
      dromedary viruses. Conclusions: Using a precision approach to public health
      surveillance, we detected and characterized the genomics of vaccine-preventable
      and zoonotic respiratory viruses associated with clusters of severe respiratory
      infections in Uganda. Future studies are needed to assess the feasibility,
      scalability, and impact of applying similar approaches during real-time public
      health surveillance in low-income settings.

PMID- 30099511
TI  - Corrigendum: Current understanding of the pathways of flavonoid biosynthesis in
      model and crop plants.

PMID- 30099512
TI  - The Zurich Checklist for Safety in the Intraoperative Magnetic Resonance Imaging
      Suite: Technical Note.
AB  - BACKGROUND: Recently, the use of intraoperative magnetic resonance imaging
      (ioMRI) has evolved in neurosurgery. Challenges related to ioMRI-augmented
      procedures are significant, since the magnetic field creates a potentially
      hazardous environment. Strict safety guidelines in the operating room (OR) are
      necessary. Checklists can minimize errors while increasing efficiency and
      improving workflow. OBJECTIVE: To describe the Zurich checklists for safety in
      the ioMRI environment. METHODS: We summarize the checklist protocol and the
      experience gained from over 300 surgical procedures performed over a 4-yr period
      using this new system for transcranial or transsphenoidal surgery in a 2-room
      high-field 3 Tesla ioMRI suite. RESULTS: Particularities of the 2-room setting
      used at our institution can be summarized as (1) patient transfer from a sterile
      to a nonsterile environment and (2) patient transfer from a zone without to a
      zone with a high-strength magnetic field. Steps on the checklist have been
      introduced for reasons of efficient workflow, safety pertaining to the strength
      of the magnetic field, or sterility concerns. Each step in the checklist
      corresponds to a specific phase and particular actions taken during the workflow
      in the ioMRI suite. Most steps are relevant to any 2-room ioMRI-OR suite.
      CONCLUSION: The use of an ioMRI-checklist promotes a zero-tolerance attitude for
      errors, can lower complications, and can help create an environment that is both
      efficient and safe for the patient and the OR personnel. We highly recommend the
      use of a surgical checklist when applying ioMRI.

PMID- 30099513
TI  - Occupational Exposure to Mycotoxins: Current Knowledge and Prospects.
AB  - Occupational exposure to mycotoxins is supposedly very frequent, but it is rarely
      reported in the scientific literature. Several recent studies described
      occupational exposure to the aflatoxin B1 (AFB1) mycotoxin in different
      occupational settings. Previously, exposure to other mycotoxins was shown in the
      animal husbandry and food processing sectors, confirming that occupational
      exposure cannot be negligible. However, no guidelines or standard methodologies
      are available for helping occupational hygienists to consider mycotoxin exposure
      in their interventions. This article reviews the literature on this problem and
      recommends some actions for the better management of this risk factor in
      occupational settings, especially where environmental conditions are favorable to
      fungal presence.

PMID- 30099514
TI  - Supplementing goat kids with coconut medium chain fatty acids in early life
      influences growth and rumen papillae development until 4 months after
      supplementation but effects on in vitro methane emissions and the rumen
      microbiota are transient.

PMID- 30099515
TI  - Feed batch sequencing to decrease the risk of porcine epidemic diarrhea virus
      (PEDV) cross-contamination during feed manufacturing.
AB  - Feed has been identified as a vector of transmission for porcine epidemic
      diarrhea virus (PEDV). The objective of this study was to determine if feed batch
      sequencing methods could minimize PEDV cross-contamination. Porcine epidemic
      diarrhea virus-free swine feed was manufactured to represent the negative
      control. A 50 kg feed batch was mixed in a pilot scale feed mill for 5 min,
      sampled, then discharged for 10 min into a bucket elevator and sampled again upon
      exit. Next, a pathogenic PEDV isolate was used to inoculate 49.5 kg of PEDV-free
      feed to form the positive control. The positive control was mixed, conveyed and
      sampled similar to the negative control. Subsequently, 4 sequence batches
      (sequence 1 to 4) were formed by adding a 50 kg batch of PEDV-negative feed to
      the mixer after the prior batch was mixed and conveyed; all sequences were mixed,
      conveyed, and sampled similar to the negative and positive control batches. None
      of the equipment was cleaned between batches within a replicate. This entire
      process was replicated 3 times with cleaning the feed mill between replicates.
      Feed was then analyzed for PEDV RNA by real-time reverse transcriptase
      semiquantitative polymerase chain reaction (rRT-PCR) as measured by cycle
      threshold (Ct) and for infectivity by bioassay. Sequence 1 feed had higher (P ?
      0.05) rRT-PCR Ct values than the positive batch and sequence 2 feed had higher (P
      ? 0.05) Ct values than sequence 1, regardless of sampled location. Feed sampled
      from the mixer from sequence 2, 3, and 4 was rRT-PCR negative whereas feed
      sampled from the bucket elevator was rRT-PCR negative from sequence 3 and 4.
      Bioassay was conducted using 66 mixed sex 10-d-old pigs confirmed negative for
      PEDV allocated to 22 different rooms. Pigs were initially 10-d old. Control pigs
      remained PEDV negative for the study. All pigs from the mixer positive batch
      (9/9) and bucket elevator positive batch (3/3) were rRT-PCR positive on fecal
      swabs by the end of the study. One replicate of pigs from mixer sequence 1 was
      rRT-PCR positive (3/3) by 7 dpi. One replicate of mixer pigs from sequence 2 was
      rRT-PCR positive (3/3) by 7 dpi although no detectable PEDV RNA was found in the
      feed. The results demonstrate sequenced batches had reduced quantities of PEDV
      RNA although sequenced feed without detectible PEDV RNA by rRT-PCR can be
      infectious. Therefore, a sequencing protocol can reduce but not eliminate the
      risk of producing infectious PEDV carryover from the first sequenced batch of
      feed.

PMID- 30099517
TI  - Temporal trends in acute kidney injury across health care settings in the Irish
      health system: a cohort study.
AB  - Background: Complete ascertainment of the true rates of acute kidney injury (AKI)
      and emerging trends are essential for planning of preventive strategies within
      health systems. Methods: We conducted a retrospective cohort study from 2005 to
      2014 using data from regional laboratory information systems to determine
      incidence rates of AKI and severity Stages 1-3 in the Irish health system.
      Multivariable models were developed to explore annual trends and the
      contributions of demographic factors, clinical measures, geographic factors and
      location of medical supervision expressed as adjusted odds ratios (ORs) and 95%
      confidence intervals (CIs). Results: From 2005 to 2014, incidence rates of AKI
      increased from 6.1% (5.8-6.3) to 13.2% (12.7-13.8) per 100 patient-years in men
      and from 5.0% (4.8-5.2) to 11.5% (11.0-12.0) in women, P < 0.001. Stage 1 AKI
      accounted for the greatest growth in incidence, from 4.4% (95% CI 4.3-4.6) in
      2005 to 10.1% (95% CI 9.8-10.5) in 2014 (P < 0.001 for trend). Compared with
      2005, patients in 2014 were more likely to experience AKI [OR 4.53 (95% CI 4.02
      5.1) for Stage 1, OR 5.22 (4.16-6.55) for Stage 2 and OR 4.11 (3.05-5.54) for
      Stage 3], adjusting for changing demographic and clinical profiles. Incidence
      rates of AKI increased in all locations of medical supervision during the period
      of observation, but were greatest for inpatient [OR 19.11 (95% CI 17.69-20.64)]
      and emergency room settings [OR 5.97 (95% CI 5.56-6.42)] compared with a general
      practice setting (referent). Conclusion: Incidence rates of AKI have increased
      substantially in the Irish health system, which were not accounted for by
      changing demographic patterns, clinical profiles or location of medical
      supervision.

PMID- 30099518
TI  - The Distance Between Forests and Crops Affects the Abundance of Drosophila
      suzukii During Fruit Ripening, But Not During Harvest.
AB  - Drosophila suzukii (Matsumura; Diptera: Drosophilidae) is an invasive pest with
      the ability to reproduce not only in various soft fruit crops, but also in
      numerous wild hosts. Forests and forest edges harbor many wild hosts, provide
      suitable microclimatic conditions and are therefore thought to enhance the
      abundance of D. suzukii. Although the comprehension of pest activity based on
      specific landscape elements is important to implement efficient management
      strategies, knowledge of how forests affect the abundance of D. suzukii in nearby
      crops is very limited. We conducted a monitoring study with liquid baited traps
      across different crops at different distance from the forests. During fruit
      ripening, more flies were captured in crops closer to forests (22.21 % decrease
      per 500 m distance), whereas there was no significant relationship during
      harvest. Since color can affect the efficiency of D. suzukii traps, we have used
      traps either with a red or black lid. Acquired data suggest that traps with black
      lids capture significantly more flies than traps with red lids. We provide a
      quantitative estimation of how and when distance from adjacent forests affects
      the abundance of D. suzukii in crop fields. Our results can help consultants and
      farmers to estimate the pest pressure of D. suzukii in crop fields near forested,
      noncrop areas and to implement appropriate control strategies when D. suzukii
      populations increase and fruit becomes susceptible to infestation.

PMID- 30099516
TI  - HLA and KIR Associations of Cervical Neoplasia.
AB  - Background: Cervical cancer is the fourth most common cancer in women, and we
      recently reported human leukocyte antigen (HLA) alleles showing strong
      associations with cervical neoplasia risk and protection. HLA ligands are
      recognized by killer immunoglobulin-like receptors (KIRs) expressed on a range of
      immune cell subsets, governing their proinflammatory activity. We hypothesized
      that the inheritance of particular HLA-KIR combinations would increase cervical
      neoplasia risk. Methods: Here, we used HLA and KIR dosages imputed from single
      nucleotide polymorphism genotype data from 2143 cervical neoplasia cases and
      13858 healthy controls of European decent. Results: The following 4 novel HLA
      alleles were identified in association with cervical neoplasia, owing to their
      linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles:
      HLA-DRB3*9901 (odds ratio [OR], 1.24; P = 2.49 * 10-9), HLA-DRB5*0101 (OR, 1.29;
      P = 2.26 * 10-8), HLA-DRB5*9901 (OR, 0.77; P = 1.90 * 10-9), and HLA-DRB3*0301
      (OR, 0.63; P = 4.06 * 10-5). We also found that homozygosity of HLA-C1 group
      alleles is a protective factor for human papillomavirus type 16 (HPV16)-related
      cervical neoplasia (C1/C1; OR, 0.79; P = .005). This protective association was
      restricted to carriers of either KIR2DL2 (OR, 0.67; P = .00045) or KIR2DS2 (OR,
      0.69; P = .0006). Conclusions: Our findings suggest that HLA-C1 group alleles
      play a role in protecting against HPV16-related cervical neoplasia, mainly
      through a KIR-mediated mechanism.

PMID- 30099519
TI  - Metabolic Outcomes in Adults Born Preterm With Very Low Birthweight or Small for
      Gestational Age at Term: A Cohort Study.
AB  - Context and Objectives: Low birthweight (LBW) has emerged as a risk factor of
      metabolic syndrome (MetS). Whether adults with very low birthweight (VLBW) born
      preterm are at higher risk than individuals who were term-born small for
      gestational age (tb-SGA) is not established. We assessed metabolic outcomes,
      including relation with skeletal parameters, in these two LBW categories. Design,
      Participants, and Outcomes: This follow-up cohort study included 189 individuals
      (females 51%), aged 25 to 28 years; 55 were preterm VLBW (<=1500 g), 59 were tb
      SGA (<10th percentile), and 75 were controls (>=10th percentile). Outcomes were
      indices of MetS: blood pressure (BP), waist circumference, fasting glucose, lipid
      profile, and association between calculated MetS score and bone mineral density
      (BMD) and trabecular bone score (TBS), a measure of bone quality. Results:
      Compared with controls, individuals with VLBW displayed higher systolic [mean
      (SD), 126 (13.3) vs 119 (12.3) mm Hg; 95% CI, 1.27 to 11.48 mm Hg] and diastolic
      [71.9 (7.6) vs 68.6 (7.1) mm Hg; 95% CI, 0.3 to 6.2 mm Hg] BP, higher glycated
      hemoglobin, higher C-peptide, increased insulin resistance (Homeostatic Model
      Assessment 2), and lower high-density lipoprotein cholesterol [1.34 (0.3) vs 1.50
      (0.4); 95% CI, 0.32 to 0.01]. Substantial differences were mainly seen between
      control females and females with VLBW. The adults who were tb-SGA had higher
      waist circumference and higher total and low-density lipoprotein cholesterol
      compared with controls. In males, MetS score correlated positively with BMD and
      inversely with TBS. Conclusions: The LBW groups and preferentially females in the
      VLBW group displayed a less favorable metabolic profile than did controls. The
      inverse association between MetS score and bone quality suggests enhanced future
      fracture risk.

PMID- 30099520
TI  - Bayesian Phylogeography and Pathogenic Characterization of Smallpox Based on HA,
      ATI, and CrmB Genes.
AB  - Variola virus is at risk of re-emergence either through accidental release,
      bioterrorism, or synthetic biology. The use of phylogenetics and phylogeography
      to support epidemic field response is expected to grow as sequencing technology
      becomes miniaturized, cheap, and ubiquitous. In this study, we aimed to explore
      the use of common VARV diagnostic targets hemagglutinin (HA), cytokine response
      modifier B (CrmB), and A-type inclusion protein (ATI) for phylogenetic
      characterization as well as the representativeness of modelling strategies in
      phylogeography to support epidemic response should smallpox re-emerge. We used
      Bayesian discrete-trait phylogeography using the most complete data set currently
      available of whole genome (n = 51) and partially sequenced (n = 20) VARV
      isolates. We show that multilocus models combining HA, ATI, and CrmB genes may
      represent a useful heuristic to differentiate between VARV Major and subclades of
      VARV Minor which have been associated with variable case-fatality rates. Where
      whole genome sequencing is unavailable, phylogeography models of HA, ATI, and
      CrmB may provide preliminary but uncertain estimates of transmission, while
      supplementing whole genome models with additional isolates sequenced only for HA
      can improve sample representativeness, maintaining similar support for
      transmission relative to whole genome models. We have also provided empirical
      evidence delineating historic international VARV transmission using
      phylogeography. Due to the persistent threat of re-emergence, our results provide
      important research for smallpox epidemic preparedness in the posteradication era
      as recommended by the World Health Organisation.

PMID- 30099521
TI  - Genomic characterization of IMP and VIM carbapenemase-encoding transferable
      plasmids of Enterobacteriaceae.
AB  - Objectives: IMP and VIM carbapenemases, in association with class 1 integrons,
      have spread globally among multiple Enterobacteriaceae species. We characterized
      IMP- and VIM-encoding transferable plasmids of clinical Enterobacteriaceae
      collected from two global surveillance programmes. Methods: We performed
      conjugation and transformation experiments for 38 IMP and 89 VIM producers.
      Plasmids, obtained from transconjugants or transformants, were sequenced with
      Illumina next-generation sequencing and analysed for replicon types and
      antimicrobial resistance genes. Results: A total of 41 transconjugants (blaIMP, n
      = 22; blaVIM, n = 19) and 10 transformants (blaIMP, n = 1; blaVIM, n = 9) were
      obtained. Broad-host-range IncL/M, IncC and IncN plasmids were associated with
      blaIMP and blaVIM, contained various integrons and showed inter-species and
      international distribution. Narrow-host-range IncFII(K) plasmids were limited to
      Klebsiella pneumoniae with blaIMP-26 from the Philippines, while IncR and IncHI1B
      IncFIB(Mar) plasmids were restricted to K. pneumoniae with blaVIM from Greece and
      Spain. IncA-like hybrid plasmids were detected in Enterobacter xiangfangensis
      from Italy and K. pneumoniae from Spain. Transferable plasmids were major
      contributors of antimicrobial resistance genes among Enterobacteriaceae with
      blaIMP and blaVIM. Conclusions: This is the first report, to the best of our
      knowledge, describing blaIMP on IncFII(K) plasmids and blaVIM on IncL/M, IncN2,
      IncHI1B-IncFIB(Mar) and IncX3-IncC-like plasmids and showed that broad-host-range
      and narrow-host-range plasmids have contributed to the global spread of blaIMP
      and blaVIM among different species. This study highlights the importance of
      molecular analysis of plasmids in providing insight into horizontal spread of
      these carbapenemases.

PMID- 30099524
TI  - WITHDRAWAL FOR "Glucose-Dependent Insulinotropic Polypeptide Increases Blood Flow
      in Adipose Tissue of Humans by Recruiting Capillaries".

PMID- 30099525
TI  - Antagonistic Roles of phyA and phyB in Far-red Light-Dependent Leaf Senescence in
      Arabidopsis thaliana.
AB  - Leaf senescence is regulated by diverse developmental and environmental factors
      to maximize plant fitness. The red to far-red light ratio (R:FR) detected by
      plant phytochromes is reduced under vegetation shade, thus initiating leaf
      senescence. However, the role of phytochromes in promoting leaf senescence under
      FR-enriched conditions is not fully understood. In this study, we investigated
      the role of phyA and phyB in regulating leaf senescence under FR in Arabidopsis
      thaliana (Arabidopsis). FR enrichment and intermittent FR pulses promoted the
      senescence of Arabidopsis leaves. Additionally, phyA and phyB mutants showed
      enhanced and repressed senescence phenotypes in FR, respectively, indicating that
      phyA and phyB antagonistically regulate FR-dependent leaf senescence.
      Transcriptomic analysis using phyA and phyB mutants in FR identified
      differentially expressed genes (DEGs) involved in leaf senescence-related
      processes, such as responses to light, phytohormones, and temperature,
      photosynthesis, and defense, showing opposite expression patterns in phyA and
      phyB mutants. These contrasting expression profiles of DEGs support the
      antagonism between phyA and phyB in FR-dependent leaf senescence. Among the genes
      showing antagonistic regulation, we confirmed that the expression of WRKY6, which
      encodes a senescence-associated transcription factor, was negatively and
      positively regulated by phyA and phyB, respectively. The wrky6 mutant showed a
      repressed senescence phenotype compared with the wild type in FR, indicating that
      WRKY6 plays a positive role in FR-dependent leaf senescence. Our results imply
      that antagonism between phyA and phyB is involved in fine-tuning leaf senescence
      under varying FR conditions in Arabidopsis.

PMID- 30099522
TI  - Clinical Characteristics and Postoperative Outcomes of Primary Aldosteronism in
      the Elderly.
AB  - Context: Primary aldosteronism (PA) in the elderly has increased in importance in
      association with population aging. Objective: To investigate the characteristics
      and outcomes of elderly patients with PA undergoing adrenalectomy. Patients and
      Methods: Using a database of patients with PA who underwent adrenal venous
      sampling (AVS), we compared elderly patients (>=65 years old) with nonelderly
      patients (<65 years old) in terms of characteristics, subtype classification in
      ACTH-stimulated AVS, and outcomes after adrenalectomy. Results: The elderly group
      had a higher prevalence of comorbidities than the nonelderly group. The
      proportion of the unilateral subtype [defined as a lateralization index (LI) >4]
      was comparable between the age groups. In patients who received adrenalectomy,
      biochemical cure was comparable between the groups, whereas persistent
      hypertension was more common in the elderly group. The prevalences of
      hyperkalemia and renal impairment (chronic kidney disease stage 3b or higher)
      were higher in the elderly group. Multiple regression analysis showed that the
      duration of hypertension predicted persistent hypertension and hyperkalemia and
      that preoperative estimated glomerular filtration rate predicted renal impairment
      in the elderly group. LI >4 in AVS was an independent predictor of biochemical
      cure after adrenalectomy in the elderly group but not in the nonelderly group.
      Age was negatively associated with biochemical cure in patients with LI <=4.
      Conclusion: Adrenalectomy contributes to biochemical improvement in elderly
      patients if determined in accordance with AVS. The treatment strategy should be
      determined considering the high postoperative incidence of persistent
      hypertension and hyperkalemia in elderly patients with a long history of
      hypertension or renal impairment in those with reduced renal function.

PMID- 30099526
TI  - Plant Cuttings.

PMID- 30099527
TI  - Letter to the editor concerning comments by Hamer and Chen on Japanese
      encephalitis: vaccine options and timing of pre-travel vaccination.

PMID- 30099528
TI  - MicroPheno: predicting environments and host phenotypes from 16S rRNA gene
      sequencing using a k-mer based representation of shallow sub-samples.

PMID- 30099529
TI  - Clinical Practice Guideline for the Medical Management of Perianal Fistulizing
      Crohn's Disease: The Toronto Consensus.
AB  - Background: Fistulas occur in about 25% of patients with Crohn's disease (CD) and
      can be difficult to treat. The aim of this consensus was to provide guidance for
      the management of patients with perianal fistulizing CD. Methods: A systematic
      literature search identified studies on the management of fistulizing CD. The
      quality of evidence and strength of recommendations were rated according to the
      Grading of Recommendation Assessment, Development and Evaluation (GRADE)
      approach. Statements were developed through an iterative online platform using a
      modified Delphi process, then finalized, and voted on by a group of specialists.
      Results: The quality of evidence for treatment of fistulizing CD was generally of
      very low quality, and because of the scarcity of good randomized controlled
      trials (RCTs), these consensus statements generally provide conditional
      suggestions (5 of 7 statements). Imaging and surgical consultations were
      recommended in the initial assessment of patients with active fistulizing CD,
      particularly those with complicated disease. Antibiotic therapy is useful for
      initial symptom control. Antitumor necrosis factor (anti-TNF) therapy was
      recommended to induce symptomatic response, and continued use was suggested to
      achieve and maintain complete remission. The use of concomitant immunosuppressant
      therapies may be useful to optimize pharmacokinetic parameters when initiating
      anti-TNF therapy. When there has been an inadequate symptomatic response to
      medical management strategies, surgical therapy may provide effective fistula
      healing for some patients. Conclusions: Optimal management of perianal
      fistulizing CD requires a collaborative effort between gastroenterologists and
      surgeons and may include the evidence-based use of existing therapies, as well as
      surgical assessments and interventions when needed.

PMID- 30099530
TI  - Reasons for disparity in statin adherence rates between clinical trials and real
      world observations: a review.
AB  - With statins, the reported rate of adverse events differs widely between
      randomized clinical trials (RCTs) and observations in clinical practice, the
      rates being 1-2% in RCTs vs. 10-20% in the so-called real world. One possible
      explanation is the claim that RCTs mostly use a run-in period with a statin. This
      would exclude intolerant patients from remaining in the trial and therefore
      favour a bias towards lower rates of intolerance. We here review data from RCTs
      with more than 1000 participants with and without a run-in period, which were
      included in the Cholesterol Treatment Trialists Collaboration. Two major
      conclusions arise: (i) the majority of RCTs did not have a test dose of a statin
      in the run-in phase. (ii) A test dose in the run-in phase was not associated with
      a significantly improved adherence rate within that trial when compared to trials
      without a test dose. Taken together, the RCTs of statins reviewed here do not
      suggest a bias towards an artificially higher adherence rate because of a run-in
      period with a test dose of the statin. Other possible explanations for the
      apparent disparity between RCTs and real-world observations are also included in
      this review albeit mostly not supported by scientific data.

PMID- 30099531
TI  - The AP-1 Complex is Required for Proper Mucilage Formation in Arabidopsis Seeds.
AB  - The adaptor protein (AP) complexes play crucial roles in vesicle formation in
      post-Golgi trafficking. Land plants have five types of AP complexes (AP-1 to AP
      5), each of which consists of two large subunits, one medium subunit and one
      small subunit. Here, we show that the Arabidopsis AP-1 complex mediates the
      polarized secretion and accumulation of a pectic polysaccharide called mucilage
      in seed coat cells. Previously, a loss-of-function mutant of AP1M2, the medium
      subunit of AP-1, has been shown to display deleterious growth defects because of
      defective cytokinesis. To investigate the function of AP-1 in interphase, we
      generated transgenic Arabidopsis plants expressing AP1M2-GFP (green fluorescent
      protein) under the control of the cytokinesis-specific KNOLLE (KN) promoter in
      the ap1m2 background. These transgenic plants, designated pKN lines, successfully
      rescued the cytokinesis defect and dwarf phenotype of ap1m2. pKN lines showed
      reduced mucilage extrusion from the seed coat. Furthermore, abnormal accumulation
      of mucilage was found in the vacuoles of the outermost integument cells of pKN
      lines. During seed development, the accumulation of AP1M2-GFP was greatly reduced
      in the integument cells of pKN lines. These results suggest that trans-Golgi
      network (TGN)-localized AP-1 is involved in the trafficking of mucilage
      components to the outer surface of seed coat cells. Our study highlights an
      evolutionarily conserved function of AP-1 in polarized sorting in eukaryotic
      cells.

PMID- 30099532
TI  - Aortic Root Dilatation Is Associated With Incident Cardiovascular Events in a
      Population of Treated Hypertensive Patients: The Campania Salute Network.
AB  - BACKGROUND: Aortic root (AR) dimension (ARD) at the Valsalva sinuses has been
      associated with incident cardiovascular (CV) events in population-based studies,
      but this effect could be due to the association with increased left ventricular
      (LV) mass. There is also uncertainty on how to define clear-cut AR dilatation.
      Thus, we analyzed the Campania Salute Network (CSN) registry to (i) establish
      criteria for evaluation of ARD, (ii) propose cut-points for AR dilatation, and
      (iii) determine whether AR dilatation has prognostic value independent of LV
      hypertrophy (LVH). METHODS: We analyzed hypertensive patients with available
      follow-up, in sinus rhythm and free of prevalent valvular and CV disease (n =
      8,573). AR exceeding the 75th percentile of the AR z-score (Ao-Z) obtained by
      comparison with the value predicted by age, sex, and height (i.e., Ao-Z > 0.80)
      was considered dilated. RESULTS: Patients with baseline-dilated ARD by Ao-Z were
      more likely to be younger, men, and obese and had higher baseline blood pressure
      (BP; all <0.02) but similar kidney function as those without ARD dilatation. In
      multivariable Cox regression model, dilated ARD predicted 36% increased rate of
      CV events, independently of older age, male sex, systolic BP, LVH, and class of
      antihypertensive medications used during follow-up (95% confidence interval: 1.07
      1.71, P = 0.011). CONCLUSIONS: In the context of a population of treated
      hypertensive patients, ARD defined by z-score of predicted values is an
      independent predictor of CV events regardless of LVH and other common
      confounders. CLINICAL TRIALS REGISTRATION: Trial Number NCT02211365.

PMID- 30099533
TI  - A Maximum-Likelihood Approach to Estimating the Insertion Frequencies of
      Transposable Elements from Population Sequencing Data.
AB  - Transposable elements (TEs) contribute to a large fraction of the expansion of
      many eukaryotic genomes due to the capability of TEs duplicating themselves
      through transposition. A first step to understanding the roles of TEs in a
      eukaryotic genome is to characterize the population-wide variation of TE
      insertions in the species. Here, we present a maximum-likelihood (ML) method for
      estimating allele frequencies and detecting selection on TE insertions in a
      diploid population, based on the genotypes at TE insertion sites detected in
      multiple individuals sampled from the population using paired-end (PE) sequencing
      reads. Tests of the method on simulated data show that it can accurately estimate
      the allele frequencies of TE insertions even when the PE sequencing is conducted
      at a relatively low coverage (=5X). The method can also detect TE insertions
      under strong selection, and the detection ability increases with sample size in a
      population, although a substantial fraction of actual TE insertions under
      selection may be undetected. Application of the ML method to genomic sequencing
      data collected from a natural Daphnia pulex population shows that, on the one
      hand, most (>90%) TE insertions present in the reference D. pulex genome are
      either fixed or nearly fixed (with allele frequencies >0.95); on the other hand,
      among the nonreference TE insertions (i.e., those detected in some individuals in
      the population but absent from the reference genome), the majority (>70%) are
      still at low frequencies (<0.1). Finally, we detected a substantial fraction
      (~9%) of nonreference TE insertions under selection.

PMID- 30099534
TI  - Risk of benign meningioma after childhood cancer in the DCOG-LATER cohort:
      contributions of radiation dose, exposed cranial volume, and age.
AB  - Background: Pediatric cranial radiotherapy (CrRT) markedly increases risk of
      meningiomas. We studied meningioma risk factors with emphasis on independent and
      joint effects of CrRT dose, exposed cranial volume, exposure age, and
      chemotherapy. Methods: The DCOG-LATER cohort includes five-year childhood cancer
      survivors (CCSs) diagnosed 1963-2001. Histologically confirmed benign meningiomas
      were identified from the population-based Dutch Pathology Registry (PALGA; 1990
      2015). We calculated cumulative meningioma incidence and used multivariable Cox
      regression and linear excess relative risk (ERR) modelling. Results: Among 5,843
      CCSs (median follow-up: 23.3 years, range: 5.0-52.2 years), 97 developed a benign
      meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared
      to CrRT doses of 1-19 Gy, no CrRT was associated with a low meningioma risk
      (HR=0.04,95%CI:0.01-0.15), while increased risks were observed for CrRT doses 20
      39 Gy (HR=1.66,95%CI:0.83-3.33) and 40+ Gy (HR=2.81,95%CI: 1.30-6.08). CCSs
      diagnosed before age 5 vs 10-17 years showed significantly increased risks
      (HR=2.38,95% CI:1.39-4.07). In this dose-adjusted model, volume was not
      significantly associated with increased risk (HR full vs. partial=1.66,95%CI:0.86
      3.22). Overall, the ERR/Gy was 0.30 (95%CI:0.03-unknown). Dose effects did not
      vary significantly according to exposure age nor CrRT volume. Cumulative
      incidence after any CrRT was 12.4% (95%CI:9.8%-15.2%) 40 years after primary
      cancer diagnosis. Among chemotherapy agents (including methotrexate and
      cisplatin), only carboplatin (HR=3.55,95%CI:1.62-7.78) appeared associated with
      meningioma risk. However, we saw no carboplatin dose-response and all nine
      exposed cases had high-dose CrRT. Conclusion: After cranial radiotherapy one in
      eight survivors developed late meningioma by age 40 years, associated with
      radiation dose- and exposure age, relevant for future treatment protocols and
      awareness among survivors and physicians.

PMID- 30099535
TI  - Early Liver Transplantation is a Viable Treatment Option in Severe Acute
      Alcoholic Hepatitis.
AB  - Liver transplantation is lifesaving for patients with severe acute alcoholic
      hepatitis (SAH) with preliminary data demonstrating favorable early post
      transplant outcomes. Using the United Network for Organ Sharing database, we
      demonstrate that liver transplantation for SAH in the USA has steadily increased
      and is associated with similar 1- and 3-year post-transplant survival as well as
      comparable 30-day waitlist mortality to acute liver failure due to drug-induced
      liver injury.

PMID- 30099536
TI  - Attitudes Toward Deafness Affect Impressions of Young Adults With Cochlear
      Implants.
AB  - This study continues a project on speech-based impressions of early-implanted
      cochlear implant (CI) users. It examined relationships between listeners'
      attitudes or personal traits and how they judged CI users upon hearing their
      speech. College students with typical hearing (TH) listened to speech samples
      from CI users and TH young adults and rated the speakers' personalities and
      attractiveness as friends. CI users varied in speech intelligibility (proportion
      of words recognized by transcribers in prior work). Overall, listeners rated TH
      speakers most positively, CI users with high intelligibility (CI-Hi) as
      intermediate, and CI users with lower intelligibility (CI-Lo) most negatively.
      Listeners also completed questionnaires about their personalities, values, and
      attitudes toward deafness. Listeners with more positive attitudes toward deaf
      people rated both CI user groups more positively, and listeners whose personality
      and values questionnaires showed more tolerance and openness to interpersonal
      differences rated CI-Lo speakers more positively. These patterns underline the
      social importance of CI users' speech intelligibility while bringing to light the
      role of listeners' pre-existing attitudes in forming negative first impressions,
      which could impact CI users' friendships with TH peers. Because listeners'
      attitudes reflected ignorance about deaf people's abilities, this study calls for
      increased education about deafness for TH students.

PMID- 30099538
TI  - Data Sciences and Informatics: What's in a name?

PMID- 30099539
TI  - General Principles for Preoperative Planning and Microsurgical Treatment of
      Pediatric Brain Arteriovenous Malformations: 2-Dimensional Operative Video.
AB  - Children with arteriovenous malformations (AVMs) are at cumulative, life-long
      risk of debilitating and fatal intracranial hemorrhage, especially with syndromes
      such as hereditary hemorrhagic telangiectasia. Cerebral angiography is the gold
      standard for diagnosis and allows simultaneous adjunctive embolization limiting
      radiation and contrast exposure and intraoperative blood loss, important in
      pediatric patients with low blood volume. Microsurgical resection of low-grade
      AVMs offers cure with minimal morbidity. The plasticity of the pediatric brain
      may allow resection of AVMs near eloquent regions. Multidisciplinary care offers
      the best outcomes in these cases. Discussion of the operative plan with all team
      members at the start of surgery is carried out. Confirmation that blood products
      are present and that the microscope, additional suction, and surgical clips are
      available is performed. A generous craniotomy is created, adequately exposing the
      lesion. The dura is carefully opened to avoid injury to draining veins.
      Circumferential dissection and isolation of the AVM is performed, coagulating
      small arterial feeders, dissecting to the lesion's apex to coagulate, and divide
      major deep feeders. Once all feeders have been obliterated, venous drainage is
      disconnected. Indocyanine green distinguishes arterial feeders from arterialized
      veins and confirms complete resection. Since 2008, all of our patients undergo
      perioperative angiography in our dedicated suite, greatly improving resection
      rates. Strict blood pressure control and close neurological monitoring in the
      intensive care unit is performed postoperatively. In conclusion, microsurgical
      resection of AVMs can be performed safely with low rates of morbidity. Protocols
      for preoperative evaluation and planning appear to improve outcomes. Anonymous
      video is permitted when done without identifying patient related information.

PMID- 30099537
TI  - Construction of a Selectable Marker Recycling System and the Use in Epitope
      Tagging of Multiple Nuclear Genes in the Unicellular Red Alga Cyanidioschyzon
      merolae.
AB  - The nuclear genome of the unicellular red alga Cyanidioschyzon merolae can be
      modified by homologous recombination with exogenously introduced DNA. However, it
      is presently difficult to modify multiple chromosome loci because of the limited
      number of available positive selectable markers. In this study, we constructed a
      modified URA5.3 gene (URA5.3T), which can be repeatedly used for nuclear genome
      transformation, as well as two plasmid vectors for 3* FLAG- or 3* Myc-epitope
      tagging of nuclear-encoded proteins using URA5.3T. In the URA5.3T marker, the
      promoter region and open reading frame were located between directly repeated
      URA5.3 terminator sequences, and the URA5.3 gene can be eliminated by 5
      fluoroorotic acid selection through homologous recombination. To demonstrate the
      utility of the constructed system, a 3* FLAG-tag and 3* Myc-tag were introduced
      at the C-termini of two of the six Rab proteins in C. merolae, CmRab18 and
      CmRab7, respectively, and the differential expression levels were successfully
      monitored by immunoblot analysis using these epitope tags. The URA5.3T marker's
      introduction and elimination cycle can be repeated. Thus, we have constructed a
      marker recycling system for C. merolae nuclear transformation. A novel procedure
      to obtain a high plating efficiency of C. merolae cells on solid gellan gum
      plates is also presented.

PMID- 30099540
TI  - Nonclinical Safety Assessment of CFZ533, a Fc-Silent Anti-CD40 Antibody, in
      Cynomolgus Monkeys.
AB  - CFZ533 is a pathway blocking, nondepleting anti-CD40 antibody that is in clinical
      development for inhibition of transplant organ rejection and therapy for
      autoimmune diseases. A 26-week GLP toxicity study in sexually mature Cynomolgus
      monkeys was conducted in order to support chronic application of CFZ533. CFZ533
      was subcutaneously administered at doses up to 150 mg/kg/week and was safe and
      generally well tolerated. CFZ533 showed no adverse effects for cardiovascular,
      respiratory, and neurobehavioral endpoints, and no changes were observed for
      blood lymphocyte and platelet counts or blood coagulation markers. In line with
      the nondepleting nature of CFZ533, CD20+ B cells in the blood were only
      marginally reduced. A complete suppression of germinal center (GC) development in
      lymph nodes and spleen was the most prominent result of post-mortem histological
      investigations. This was corroborated by an abrogated T-dependent antibody
      response (TDAR) to the antigen Keyhole Limpet Hemocyanin (KLH) as well as an
      absence of anti-drug antibodies (ADAs) in the absence of B cell depletion as seen
      with immunophenotyping and histology. When serum levels of CFZ533 in recovery
      animals dropped levels necessary for full CD40 occupancy on B cells, all animals
      were able to mount a TDAR to KLH. All histological changes also reverted to
      normal appearance after recovery. In summary, CFZ533 was shown to be well
      tolerated and safe in the 26-week toxicity study with a distinct pharmacodynamic
      profile in histology and immune function.

PMID- 30099542
TI  - Prompts to increase physical activity at points-of-choice between stairs and
      escalators: what about escalator climbers?
AB  - Since 1980, many studies have evaluated whether stair-use prompts increased
      physical activity by quantifying changes in stair use. To more completely
      evaluate changes in physical activity, this study addressed the often-overlooked
      assessment of climbing up escalators by evaluating the degree to which stair-use
      sign prompts increased active ascent-defined as stair use or escalator climbing.
      Over 5 months, at an airport stairs/escalator point of choice, we video-recorded
      passersby (N = 13,544) who ascended either stairs or escalators, on 10 days with
      signs and 10 days without signs. Ascenders using the stairs, standing on the
      escalator, and climbing the escalator were compared on days with versus without
      signs using multivariable logistic regression. The percentage of ascenders on
      days with versus without signs were as follows: stair use, 6.9 versus 3.6
      percent; escalator standing, 75.2 versus 76.0 percent; and escalator climbing,
      18.5 versus 20.4 percent. Signs more than doubled the odds of stair use (vs.
      escalator use; OR = 2.25; 95% CI = 1.90-2.68; p < .001). Signs decreased the odds
      of escalator climbing (vs. escalator standing or stair use); OR = 0.90; 95% CI =
      0.82-0.99; p = .028). Signs increased the odds of active ascent versus escalator
      standing by 15 percent (OR = 1.15; 95% CI = 1.05-1.25; p = .002). Although stair
      use prompts increased stair use more than twofold (125%), they increased active
      ascent by only 15 percent, partly because escalator climbing-a behavior not
      targeted by the intervention-decreased. Although our results corroborated the
      established consensus that point-of-choice prompts increase stair use, future
      studies should test interventions designed to increase active ascent.

PMID- 30099541
TI  - Triple-Negative Breast Cancer Risk Genes Identified by Multigene Hereditary
      Cancer Panel Testing.
AB  - Background: Germline genetic testing with hereditary cancer gene panels can
      identify women at increased risk of breast cancer. However, those at increased
      risk of triple-negative (estrogen receptor-negative, progesterone receptor
      negative, human epidermal growth factor receptor-negative) breast cancer (TNBC)
      cannot be identified because predisposition genes for TNBC, other than BRCA1,
      have not been established. The aim of this study was to define the cancer panel
      genes associated with increased risk of TNBC. Methods: Multigene panel testing
      for 21 genes in 8753 TNBC patients was performed by a clinical testing
      laboratory, and testing for 17 genes in 2148 patients was conducted by a Triple
      Negative Breast Cancer Consortium (TNBCC) of research studies. Associations
      between deleterious mutations in cancer predisposition genes and TNBC were
      evaluated using results from TNBC patients and reference controls. Results:
      Germline pathogenic variants in BARD1, BRCA1, BRCA2, PALB2, and RAD51D were
      associated with high risk (odds ratio > 5.0) of TNBC and greater than 20%
      lifetime risk for overall breast cancer among Caucasians. Pathogenic variants in
      BRIP1, RAD51C, and TP53 were associated with moderate risk (odds ratio > 2) of
      TNBC. Similar trends were observed for the African American population.
      Pathogenic variants in these TNBC genes were detected in 12.0% (3.7% non-BRCA1/2)
      of all participants. Conclusions: Multigene hereditary cancer panel testing can
      identify women with elevated risk of TNBC due to mutations in BARD1, BRCA1,
      BRCA2, PALB2, and RAD51D. These women can potentially benefit from improved
      screening, risk management, and cancer prevention strategies. Patients with
      mutations may also benefit from specific targeted therapeutic strategies.

PMID- 30099543
TI  - Associations and Heritability of Auditory Encoding, Gray Matter, and Attention in
      Schizophrenia.
AB  - Background: Auditory encoding abnormalities, gray-matter loss, and cognitive
      deficits are all candidate schizophrenia (SZ) endophenotypes. This study
      evaluated associations between and heritability of auditory network attributes
      (function and structure) and attention in healthy controls (HC), SZ patients, and
      unaffected relatives (UR).  Methods: Whole-brain maps of M100 auditory activity
      from magnetoencephalography recordings, cortical thickness (CT), and a measure of
      attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability
      estimates (h2r) were obtained for M100, CT at each group-difference region, and
      the attention measure.  Results: SZ patients had weaker bilateral superior
      temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100
      response than UR. Abnormally large M100 responses in left superior frontal gyrus
      were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral
      STG and right frontal regions. Interrelatedness between 3 putative SZ
      endophenotypes was demonstrated, although in the left STG the M100 and CT
      function-structure associations observed in HC and UR were absent in SZ patients.
      Heritability analyses also showed that right frontal M100 and bilateral STG CT
      measures are significantly heritable.  Conclusions: Present findings indicated
      that the 3 SZ endophenotypes examined are not isolated markers of pathology but
      instead are connected. The pattern of auditory encoding group differences and the
      pattern of brain function-structure associations differ as a function of brain
      region, indicating the need for regional specificity when studying these
      endophenotypes, and with the presence of left STG function-structure associations
      in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray
      matter that disrupts function-structure relationships in SZ.

PMID- 30099544
TI  - Robotic-Assisted Spine Surgery Using the Mazor XTM System: 2-Dimensional
      Operative Video.
AB  - We demonstrate the setup and workflow of performing robotic spine surgery using
      the Mazor XTM system (MAZOR Robotics Inc, Orlando, Florida) in this video. An
      illustrative case was presented, including detailed steps for S2AI screw and
      lumbar pedicle screw placement using robotic assistance. A step-by-step narration
      is provided along with discussion of surgical nuances. Robotic spine surgery can
      be a safe and efficient method for screw placement, which can potentially reduce
      the risk of screw malposition. Spine surgeons should be familiar with this
      technology and keep this technique in their armamentarium.There is no identifying
      information in this video. A patient consent was obtained for publishing of the
      material included in the video.

PMID- 30099545
TI  - Germ Cell-Specific Retinoic Acid Receptor alpha Functions in Germ Cell
      Organization, Meiotic Integrity, and Spermatogonia.
AB  - Retinoic acid receptor alpha (RARA), a retinoic acid-dependent transcription
      factor, is expressed in both somatic and germ cells of the testis. Rara-null male
      mice with global Rara mutations displayed severely degenerated testis and
      infertility phenotypes. To elucidate the specific responsibility of germ cell
      RARA in spermatogenesis, Rara was deleted in germ cells, generating germ cell
      specific Rara conditional knockout (cKO) mice. These Rara cKO animals exhibited
      phenotypes of quantitatively reduced epididymal sperm counts and disorganized
      germ cell layers in the seminiferous tubules, which worsened with aging. Abnormal
      tubules lacked lumen, contained vacuoles, and showed massive germ cell sloughing,
      all characteristics similar to those observed in Rara-null tubules. Spermatocyte
      chromosomal spreads revealed a novel role for germ cell RARA in modulating the
      integrity of synaptonemal complexes and meiotic progression. Furthermore, the
      initiation of spermatogenesis from spermatogonial stem cells was decreased in
      Rara cKO testes following busulfan treatment, supporting a role of germ cell RARA
      in spermatogonial proliferation. Collectively, the evidence in this study
      indicates that RARA produced in male germ cells has a broad spectrum of functions
      throughout spermatogenesis, which includes the maintenance of seminiferous
      epithelium organization, the integrity of the meiotic genome, and spermatogonial
      proliferation and differentiation. The results further suggest that germ cell
      RARA has dual functions: intrinsically in germ cells, balancing proliferation and
      differentiation of spermatogonia, and controlling genome integrity during
      meiosis; and extrinsically in the crosstalks with Sertoli cells, controlling the
      cell junctional physiology for coordinating proper spatial and temporal
      development of germ cells during spermatogenesis.

PMID- 30099547
TI  - The effect of zolpidem on cognitive function and postural control at high
      altitude.
AB  - Study Objectives: Sleep is altered at high altitude leading many mountaineers to
      use hypnotics in order to improve sleep efficiency. While after a full night at
      altitude the short-acting hypnotic zolpidem does not appear to alter cognitive
      function, residual adverse effects should be considered following early waking-up
      as performed by mountaineers. We hypothesized that zolpidem intake at high
      altitude would alter cognitive function 4 hours after drug intake. Methods: In a
      randomized double-blind controlled cross-over study, 22 participants were
      evaluated during two nights at sea level and two nights at 3800 m, 4 hours after
      zolpidem (10 mg) or placebo intake at 10:00 pm. Polygraphic recording was
      performed until waking-up at 01:30 am. Sleep quality, sleepiness and symptoms of
      acute mountain sickness were assessed by questionnaires. Two cognitive tasks
      (Simon task and duration-production task) were performed at rest and during
      exercise and postural control was evaluated. Results: Zolpidem increased reaction
      time in all conditions (zolpidem 407 +/- 9 ms vs. placebo 380 +/- 11 ms; p <
      0.001) and error rate in incongruent trials only (10.2 +/- 1.1% vs. 7.8 +/- 0.8%;
      p < 0.01) in the Simon task and increased time perception variability (p <
      0.001). Zolpidem also altered postural parameters (e.g. center of pressure area,
      zolpidem 236 +/- 171.5 mm2 vs. placebo 119.6 +/- 59 mm2; p < 0.001). Zolpidem did
      not affect apnea-hypopnea index and mean arterial oxygen saturation (p > 0.05)
      but increased sleep quality (p < 0.001). Zolpidem increased symptoms of acute
      mountain sickness and sleepiness (p < 0.05). Conclusions: Acute zolpidem intake
      at high altitude alters cognitive functions and postural control during early
      wakening which may be deleterious for safety and performances of climbers.

PMID- 30099546
TI  - Stimulatory TSH-Receptor Antibodies and Oxidative Stress in Graves Disease.
AB  - Context: We hypothesized that TSH-receptor (TSHR) stimulating antibodies (TSAbs)
      are involved in oxidative stress mechanisms in patients with Graves disease (GD).
      Methods: Nicotinamide adenine dinucleotide phosphate oxidase, isoform 2 (NOX2);
      oxidative parameters; and oxidative burst were measured in serum, urine, and
      whole blood from patients with GD and control subjects. Superoxide production was
      investigated in human embryonic kidney (HEK)-293 cells stably overexpressing the
      TSHR. Lipid peroxidation was determined by immunodot-blot analysis for protein
      bound 4-hydroxy-2-nonenal (4-HNE) in human primary thyrocytes and HEK-293-TSHR
      cells. Results: Serum NOX2 levels were markedly higher in hyperthyroid untreated
      vs euthyroid treated patients with GD, hyperthyroid patients with toxic nodular
      goiter, and euthyroid healthy control subjects (all P < 0.0001). Urine oxidative
      parameters were increased in patients with GD vs patients with toxic goiter (P <
      0.01) and/or control subjects (P < 0.001). The maximum of the zymosan A- and
      phorbol 12,13-dibutyrate-induced respiratory burst of leukocytes was 1.5-fold
      higher in whole blood from hyperthyroid patients with GD compared with control
      subjects (P < 0.001 and P < 0.05). Monoclonal M22 TSAbs stimulated cAMP (HEK
      cells) in a dose-dependent manner. M22 (P = 0.0082), bovine TSH (P = 0.0028), and
      sera of hyperthyroid patients with GD (P < 0.05) increased superoxide-specific 2
      hydroxyethidium levels in HEK-293 TSHR cells after 48-hour incubation vs control
      subjects. In contrast, triiodothyronine (T3) did not affect reactive oxygen
      species (ROS) production. In primary thyrocytes, the 4-HNE marker was higher in
      patients with GD vs control subjects at 6 and 48 hours (P = 0.02 and P = 0.04,
      respectively). Further, after 48-hour incubation of HEK-293 TSHR cells with
      patient sera, 4-HNE was higher in patients with untreated GD compared with
      control subjects (P < 0.05). Conclusions: Monoclonal M22 and polyclonal serum
      TSAbs augment ROS generation and/or induce lipid peroxidation.

PMID- 30099549
TI  - Transcriptomic insight into nitrogen uptake and metabolism of Populus simonii in
      response to drought and low nitrogen stresses.
AB  - Understanding the regulation of plant responses to drought and low nitrogen (N)
      stresses is necessary to improve N use in water-limited lands, maintaining the
      sustainable and healthy development of ecosystems. In the present study, we
      investigated morphological, physiological and transcriptome changes in Populus
      simonii Carr. root responding to long-term drought and low N stresses. Both
      stresses resulted in lower net photosynthetic rates, chlorophyll content and
      total dry weight. Transcriptome analysis of fine roots identified 4642 genes that
      were differentially expressed in response to drought and/or low N stresses. Most
      ammonium transporters had high transcript abundances in response to drought
      and/or low N stress; meanwhile the ratio of ammonium to nitrate concentrations
      was increased under drought condition. Data of N uptakes and metabolism further
      supported that fine roots under drought stress increased ammonium uptake, and the
      aspartate-derived amino acid pathway might play a key role in tolerating drought
      stress in poplar roots. The large-scale dataset in this study presents a global
      view of the critical pathways involved in drought and low N stress. When linked
      with physiology and metabolomics data, these results provide new insights into
      the modulation of N uptake, metabolism and storage, and events within the N
      related pathways for transportation, assimilation and amino acid metabolism.

PMID- 30099548
TI  - Celiac Autoimmunity Is Associated With Lower Blood Pressure and Renal Risk in
      Type 1 Diabetes.
AB  - Context: Though the long-term consequences of celiac disease (CD) in type 1
      diabetes are unclear, CD has been associated with increased prevalence of end
      stage renal disease (ESRD) independent of type 1 diabetes. Objective: We
      evaluated whether celiac autoimmunity is related to the cumulative incidence of
      microalbuminuria [albumin excretion rate (AER) 20 to 200 ug/min],
      macroalbuminuria (AER >200 ug/min), and ESRD. Design, Patients, and Methods: In
      the prospective follow-up of the Pittsburgh Epidemiology of Diabetes
      Complications study of childhood-onset type 1 diabetes, 618 participants were
      screened for tissue transglutaminase (tTG) antibodies with a clinical assay.
      Nephropathy outcomes were determined at 25 years of diabetes duration. Results:
      Overall, the 33 subjects (5.3%) with strongly positive tTG levels (>=3 times the
      upper limit of normal) or a reported clinical history of CD had lower baseline
      blood pressure and lipid values. At 25 years of diabetes duration, a lower
      cumulative incidence of macroalbuminuria in strongly positive subjects compared
      with those with negative serology (3.6% vs 30.0%; P = 0.003) remained significant
      after adjustment for age, HbA1c, lipid measures, and blood pressure (adjusted P =
      0.004). No considerable differences between these subjects and tTG-negative
      groups were found for microalbuminuria (40.0% vs 57.1%) or ESRD (0 vs 4.1%).
      Conclusions: These findings show that strongly positive celiac autoimmunity
      status in individuals with childhood-onset type 1 diabetes is associated with
      lower baseline blood pressure and cholesterol measurements as well as lower
      macroalbuminuria risk after 25 years of type 1 diabetes duration with no increase
      in the risk of microalbuminuria or ESRD.

PMID- 30099550
TI  - Genome-wide association study of lung lesions and pleurisy in New Zealand lambs.
AB  - Pneumonia is an important issue for sheep production, leading to reduced growth
      rate and a predisposition to pleurisy. The objective of this study was to
      identify loci associated with pneumonic lesions and pleurisy in New Zealand
      progeny test lambs. The lungs from 3,572 progeny-test lambs were scored for
      presence and severity of pneumonic lesions and pleurisy at slaughter. Animals
      were genotyped using the Illumina Ovine Infinium HD SNP BeadChip (606,006
      markers). The heritability of lung lesion score and pleurisy were calculated
      using the genomic relationship matrix, and genome-wide association analyses were
      conducted using EMMAX and haplotype trend regression. At slaughter, 35% of lambs
      had pneumonic lesions, with 9% showing lesions on more than half of any
      individual lobe. The number of lambs recorded as having pleurisy by the
      processing plants was 9%. Heritability estimates for pneumonic lesions and
      pleurisy scores adjusted for heteroscedasticity (CPSa and PLEURa) were 0.16 (+/-
      0.03) and 0.05 (+/- 0.02), respectively. Five single-nucleotide polymorphisms
      (SNPs) were significantly associated with pneumonic lesions at the genome-wide
      level, and additional 37 SNPs were suggestively significant. Four SNPs were
      significantly associated with pleurisy, with an additional 11 SNPs reaching the
      suggestive level of significance. There were no regions that overlapped between
      the 2 traits. Multiple SNPs were in regions that contained genes involved in
      either the DNA damage response or the innate immune response, including several
      that had previously been reported to have associations with respiratory disease.
      Both EMMAX and HTR analyses of pleurisy data showed a significant peak on
      chromosome 2, located downstream from the transcription factor SP3. SP3 activates
      or suppresses the expression of numerous genes, including several genes with
      known functions in the immune system. This study identified several SNPs
      associated with genes involved in both the innate immune response and the
      response to DNA damage that are associated with pneumonic lesions and pleurisy in
      lambs at slaughter. Additionally, the identification in sheep of several SNPs
      within genes that have previously been associated with the respiratory system in
      cattle, pigs, rats, and mice indicates that there may be common pathways that
      underlie the response to invasion by respiratory pathogens in multiple species.

PMID- 30099552
TI  - Making Sense of... the Microbiome in Psychiatry.
AB  - Microorganisms can be found almost anywhere, including in and on the human body.
      The collection of microorganisms associated with a certain location is called a
      microbiota with its collective genetic material referred to as the microbiome.
      The largest population of microorganisms on the human body resides in the
      gastrointestinal tract thus it is not surprising that most investigated human
      microbiome is the human gut microbiome. On average, the gut hosts microbes from
      more than 60 genera and contains more cells than the human body. The human gut
      microbiome has been shown to influence many aspects of host health including more
      recently the brain.Several modes of interaction between the gut and the brain
      have been discovered, including via the synthesis of metabolites and
      neurotransmitters, activation of the vagus nerve and activation of the immune
      system. A growing body of work is implicating the microbiome in a variety of
      psychological processes and neuropsychiatric disorders. These include mood and
      anxiety disorders, neurodevelopmental disorders such as autism spectrum disorder
      and schizophrenia, and even neurodegenerative disorders such as Alzheimer's and
      Parkinson's Disease. Moreover, it is probable that most psychotropic medications
      have an impact on the microbiome.Here, an overview will be provided for the
      bidirectional role of the microbiome in brain health, age-associated cognitive
      decline, neurological and psychiatric disorders. Furthermore, a primer on the
      common microbiological and bioinformatics techniques used to interrogate the
      microbiome will be provided. This review is meant to equip the reader with a
      primer to this exciting research area which is permeating all areas of biological
      psychiatry research.

PMID- 30099553
TI  - The role of antimicrobial peptides in plant immunity.
AB  - Selective pressure imposed by millions of years of relentless biological attack
      has led to the development of an extraordinary array of defense strategies in
      plants. Among these, antimicrobial peptides (AMPs) stand out as one of the most
      prominent components of the plant immune system. These small and usually basic
      peptides are deployed as a generalist defense strategy that grants direct and
      durable resistance against biotic stress. Even though their name implies a
      function against microbes, the range of plant-associated organisms affected by
      these peptides is much broader. In this review, we highlight the advances in our
      understanding on the role of AMPs in plant immunity. We demonstrate that the
      capacity of plant AMPs to act against a large spectrum of enemies relies on their
      diverse mechanism of action and remarkable structural stability. The efficacy of
      AMPs as a defense strategy is evidenced by their widespread occurrence in the
      plant kingdom, an astonishing heterogeneity in host peptide composition, and the
      extent to which plant enemies have evolved effective counter-measures to evade
      AMP action. Plant AMPs are becoming an important topic of research due to their
      significance in allowing plants to thrive and for their enormous potential in
      agronomical and pharmaceutical fields.

PMID- 30099554
TI  - Comparison of empirical therapy with cefoperazone/sulbactam or a carbapenem for
      bloodstream infections due to ESBL-producing Enterobacteriaceae.
AB  - Objectives: Carbapenems are widely recommended for the treatment of infections
      caused by ESBL producers however, non-carbapenem beta-lactams such as beta
      lactam/beta-lactamase inhibitor combinations (BLBLIs) deserve consideration for
      the treatment of ESBL infections. Cefoperazone/sulbactam is one of the most
      commonly used BLBLIs in China; however, few outcome studies have been reported.
      In this study, we evaluated and compared the clinical efficacy of
      cefoperazone/sulbactam with that of a carbapenem in the treatment of bloodstream
      infections (BSIs) caused by ESBL-producing Enterobacteriaceae. Methods: Patients
      with monomicrobial ESBL-producing Enterobacteriaceae BSIs empirically treated
      with cefoperazone/sulbactam or a carbapenem were included. Outcomes of interest
      were clinical response and 14 day mortality. To make a comparison of the efficacy
      of cefoperazone/sulbactam and a carbapenem more accurate, propensity score
      analysis was performed. Results: No statistically significant differences in
      success rates or 14 day mortality were found between the cefoperazone/sulbactam
      (n = 17) and carbapenem (n = 46) groups. In the propensity score analysis with 17
      case-control pairs, the success rate in the cefoperazone/sulbactam group (70.6%,
      12/17) was lower than that in the carbapenem group (94.1%, 16/17), but the
      difference was not significant (P = 0.175). Sepsis-related mortality and 14 day
      mortality rates did not significantly differ either (P = 1.000 for both). In the
      cefoperazone/sulbactam group, 66.7% (2/3) of the patients with a Pitt bacteraemia
      score >=5 died within 14 days, whereas none (0/14) of the patients with a Pitt
      bacteraemia score <5 died within 14 days (P = 0.022). Conclusions: This study
      showed that cefoperazone/sulbactam had a lower success rate and a higher 14 day
      mortality rate compared with carbapenems, although the differences were not
      statistically significant because of the small patient numbers. Further
      evaluation of cefoperazone/sulbactam is needed.

PMID- 30099551
TI  - Piercing Fishes: Porin Expansion and Adaptation to Hematophagy in the Vampire
      Snail Cumia reticulata.
AB  - Cytolytic pore-forming proteins are widespread in living organisms, being mostly
      involved in both sides of the host-pathogen interaction, either contributing to
      the innate defense or promoting infection. In venomous organisms, such as
      spiders, insects, scorpions, and sea anemones, pore-forming proteins are often
      secreted as key components of the venom. Coluporins are pore-forming proteins
      recently discovered in the Mediterranean hematophagous snail Cumia reticulata
      (Colubrariidae), highly expressed in the salivary glands that discharge their
      secretion at close contact with the host. To understand their putative functional
      role, we investigated coluporins' molecular diversity and evolutionary patterns.
      Coluporins is a well-diversified family including at least 30 proteins, with an
      overall low sequence similarity but sharing a remarkably conserved actinoporin
      like predicted structure. Tracking the evolutionary history of the molluscan
      porin genes revealed a scattered distribution of this family, which is present in
      some other lineages of predatory gastropods, including venomous conoidean snails.
      Comparative transcriptomic analyses highlighted the expansion of porin genes as a
      lineage-specific feature of colubrariids. Coluporins seem to have evolved from a
      single ancestral porin gene present in the latest common ancestor of all
      Caenogastropoda, undergoing massive expansion and diversification in this
      colubrariid lineage through repeated gene duplication events paired with
      widespread episodic positive selection. As for other parasites, these findings
      are congruent with a "one-sided arms race," equipping the parasite with multiple
      variants in order to broaden its host spectrum. Overall, our results pinpoint a
      crucial adaptive role for coluporins in the evolution of the peculiar trophic
      ecology of vampire snails.

PMID- 30099555
TI  - The "House of Quality for Behavioral Science"-a user-centered tool to design
      behavioral interventions.
AB  - Within the behavioral field, a plethora of conceptual frameworks and tools have
      been developed to improve transition from efficacy to effectiveness trials;
      however, they are limited in their ability to support new, iterative intervention
      design decision-making methodologies beyond traditional randomized controlled
      trial design. Emerging theories suggest that researchers should employ
      engineering based user-centered design (UCD) methods to support more iterative
      intervention design decision-making in the behavioral field. We present, an
      adaptation of a UCD tool used in the engineering field-the Quality Function
      Deployment "House of Quality" correlation matrix, to support iterative
      intervention design decision-making and documentation for multicomponent
      behavioral interventions and factorial trial designs. We provide a detailed
      description of the adapted tool-"House of Quality for Behavioral Science", and a
      step-by-step use-case scenario to demonstrate the early identification of
      intervention flaws and prioritization of requirements. Four intervention design
      flaws were identified via the tool application. Completion of the relationship
      correlation matrix increased requirement ranking variance for the researcher
      (sigma2 = 0.47 to 7.19) and participant (sigma2 = 0.56 to 3.89) perspective.
      Requirement prioritization (ranking) was facilitated by factoring in the strength
      of the correlation between each perspective and corresponding importance. A
      correlational matrix tool such as the "House of Quality for Behavioral Science"
      may provide a structured, UCD approach that balances researcher and participant
      needs and identifies design flaws for pragmatic behavioral intervention design.
      This tool may support iterative design decision-making for multicomponent and
      factorial trial designs.

PMID- 30099556
TI  - Far Lateral Craniotomy for Posterior Inferior Cerebellar Artery-Posterior
      Inferior Cerebellar Artery Bypass and Trapping of Posterior Inferior Cerebellar
      Artery Aneurysm: 3-Dimensional Operative Video.
AB  - Posterior inferior cerebellar artery (PICA) aneurysms account for 3% to 4% of all
      intracranial aneurysms with an unusually high predilection towards a nonsaccular
      morphology making microsurgical clipping or endovascular reconstruction of the
      parent artery difficult. The management of these complicated aneurysms may
      require revascularization procedures for flow preservation with aneurysm
      trapping. Recently, there is an increasing inclination towards intracranial
      intracranial (IC-IC) bypasses over traditional extracranial donors. This video
      demonstrates a side-to-side PICA-PICA in situ bypass with trapping of an
      unruptured incidental right p1-PICA aneurysm. Radiological lesion progression and
      presence of dysplastic morphological characteristics prompted surgical
      management. The aneurysm was not amenable to clip reconstruction due to the
      dysplastic PICA segment and lack of a discernable neck. Institutional Review
      Board approval and patient consent were sought. With patient in three-quarter
      prone position, a right far lateral craniotomy was performed. A left-to-right p3
      p3 PICA bypass was completed. The aneurysm was clipped along with proximal PICA
      at its takeoff from vertebral artery. Indocyanine green videoangiography revealed
      complete occlusion of aneurysm and proximal PICA and a patent anastomosis with
      distal right PICA flow. Postoperatively, patient recovered with no new
      neurological deficits. Dolichoectatic posterior circulation aneurysms are not
      readily amenable to clip reconstruction. PICA-PICA in situ bypass is an elegant
      alternative to existing extracranial-intracranial revascularization constructs
      (occipital artery to PICA).1 There is lower neurological morbidity associated
      with IC-IC bypass vs PICA reimplantation due to the deep surgical corridor and
      its proximity to lower cranial nerves. Additionally, in this patient endovascular
      occlusion posed a higher risk of thrombotic complications and postprocedural
      cerebellar edema with brainstem compression.2.

PMID- 30099557
TI  - Gender differences in utilization of services and tobacco cessation outcomes at a
      state quitline.
AB  - Research suggests that women may have poorer tobacco cessation outcomes than men;
      however, the literature is somewhat mixed. Less is known about gender differences
      in cessation within quitline settings. This study examined gender differences in
      the utilization of services (i.e., coaching sessions, pharmacotherapy) and
      tobacco cessation among callers to the Arizona Smokers' Helpline (ASHLine). The
      study sample included callers enrolled in ASHLine between January 2011 and June
      2016. We tracked number of completed coaching sessions. At the 7-month follow-up,
      callers retrospectively reported use of cessation pharmacotherapy (gum, patch, or
      lozenge), as well as current tobacco use. Associations between gender and tobacco
      cessation were tested using logistic regression models. At month 7, 36.4% of
      women (3,277/9,004) and 40.3% of men (2,960/7,341) self-reported 30-day point
      prevalence abstinence. Compared to men, fewer women reported using
      pharmacotherapy (women: 71.4% vs. men: 73.6%, p = .01) and completed at least
      five coaching sessions (women: 35.1% vs. men: 38.5%, p < .01). After adjusting
      for baseline characteristics, women had significantly lower odds of reporting
      tobacco cessation than men (OR = 0.91, 95% CI: 0.84 to 0.99). However, after
      further adjustment for use of pharmacotherapy and coaching, there was no longer a
      significant relationship between gender and tobacco cessation (OR: 0.96, 95% CI:
      0.87 to 1.06). Fewer women than men reported tobacco cessation. Women also had
      lower utilization of quitline cessation services. Although the magnitude of these
      differences were small, future research on improving the utilization of quitline
      services among women may be worth pursuing given the large-scale effects of
      tobacco.

PMID- 30099558
TI  - Increased root investment can explain the higher survival of seedlings of 'mesic'
      Quercus suber than 'xeric' Quercus ilex in sandy soils during a summer drought.
AB  - In Mediterranean-type ecosystems, drought is considered the main ecological
      filter for seedling establishment. The evergreen oaks Quercus ilex L. and Quercus
      suber L. are two of the most abundant tree species in the Mediterranean Basin.
      Despite their shared evergreen leaf habit and ability to resist low soil water
      potentials, traditionally it has been suggested that Q. ilex is better suited to
      resist dry conditions than Q. suber. In this study, we examined how seedlings of
      Q. ilex and Q. suber grown in sandy soils responded to different levels of water
      availability using natural dry conditions and supplemental watering.
      Specifically, we estimated survival and water status of seedlings and explored
      the role of acorn mass and belowground biomass in seedling performance. To our
      surprise, Q. suber was better able to survive the summer drought in our
      experiment than Q. ilex. Nearly 55% of the Q. suber seedlings remained alive
      after a 2-month period without rain or supplemental water, which represents
      almost 20% higher survival than Q. ilex over the same period. At the end of the
      dry period, the surviving seedlings of Q. suber had strikingly higher water
      potential, potential maximum quantum yield of photosystem II (Fv/Fm) and stomatal
      conductance (gs) than those of Q. ilex. Acorn mass was associated with the
      probability of survival under dry conditions; however, it did not explain the
      differences in survival or water status between the species. In contrast, Q.
      suber had a higher root ratio and root:shoot ratio than Q. ilex and these traits
      were positively associated with predawn leaf water potential, Fv/Fm, gs and
      survival. Taken together, our results suggest that the higher relative investment
      in roots by Q. suber when growing in a sandy acidic substrate allowed this
      species to maintain better physiological status and overall condition than Q.
      ilex, increasing its probability of survival in dry conditions.

PMID- 30099560
TI  - RADIATION DOSE FROM DENTAL RADIOGRAPHY IN INDONESIA: A FIVE-YEAR SURVEY.
AB  - Dose metrics on intraoral and panoramic dental radiography were analyzed to
      preliminarily indicate dose trend of dental radiology equipment in Indonesia.
      Measurements were performed in 71 healthcare institutions involving a total of 92
      dental X-ray devices. Imaging modes are categorized into 'low dose' and 'high
      dose' based on the task. The 75th percentile for intraoral IAK was 2.8 and 4.3
      mGy for 'low' and 'high' dose modes, respectively while for panoramic devices the
      75th percentile of the KAP for 'low' and 'high' dose modes were 85.2 and 192.4
      mGy cm2, respectively. Results compared with local regulatory recommendation for
      intraoral units indicated that 38.8 and 6.3% of measured dose modes on analogue
      and digital devices, respectively, were above the recommended range. The dose
      trend can be used as reference for local regulations concerning patient dose in
      dental radiography and preliminary value prior to the establishment of national
      diagnostic reference level.

PMID- 30099561
TI  - RADIATION HAZARDS FROM CRITICALITY ACCIDENT IN OPEN POOL TYPE REACTOR.
AB  - In this study, a hypothetical nuclear criticality accident has occurred in open
      pool type reactor due to ejection of the control rod during loss of coolant
      accident. Dose rate distribution was determined for prompt neutrons and gamma
      rays resulting from first radiation pulse of the criticality accident. MCNP code
      has been used to determine the dose rate in different positions that the worker
      may locate inside the reactor during the accident. The results show that the
      maximum radiation dose is 2.52 Sv which located at the center of the top of the
      main pool. The worker located in the control room, the first floor and the ground
      floor will receive a dose of 68.2, 11.6 and 0.85 mSv, respectively. The worker
      located in the underground floor will receive a dose of 35 MUSv. SKYDOSE and
      SKYNEUT codes were used to determine the dose distribution outside the reactor
      building resulting from skyshine effect where the shielding around the reactor
      core is sufficient to attenuate the radiation in the radial direction. MCNP code
      was used to verify the SKYDOSE and SKYNEUT results along the distance of 1200 m
      from the reactor. The results show that the person around the reactor would
      receive an accumulated dose ranged between 1776.7 and 0.02 MUSv along the
      distance between 20 and 1200 m.

PMID- 30099559
TI  - The pathway of transmembrane cadmium influx via calcium-permeable channels and
      its spatial characteristics along rice root.
AB  - To develop elite crops with low cadmium (Cd), a fundamental understanding of the
      mechanism of Cd uptake by crop roots is necessary. Here, a new mechanism for Cd2+
      entry into rice root cells was investigated. The results showed that Cd2+ influx
      in rice roots exhibited spatially and temporally dynamic patterns. There was a
      clear longitudinal variation in Cd uptake along rice roots, with the root tip
      showing much higher Cd2+ influx and concentration than the root mature zone,
      which might be due to the much higher expression of the well-known Cd transporter
      genes OsIRT1, OsNRAMP1, OsNRAMP5, and OsZIP1 in the root tip. Both the net Cd2+
      influx and the uptake of Cd in rice roots were highly inhibited by ion channel
      blockers Gd3+ and TEA+, supplementation of Ca2+ and K+, and the plasma membrane
      H+-ATPase inhibitor vanadate, with Gd3+ and Ca2+ showing the most inhibitory
      effects. Furthermore, Ca2+- or Gd3+-induced reduction in Cd2+ influx and Cd
      uptake did not coincide with the expression of Cd transporter genes, but with
      that of two Ca channel genes, OsAAN4 and OsGLR3.4. These results indicate that Cd
      transporters are in part responsible for Cd2+ entry into rice root, and provide a
      new perspective that the Ca channels OsAAN4 and OsGLR3.4 might play an important
      role in rice root Cd uptake.

PMID- 30099562
TI  - Interhemispheric Approaches to Arteriovenous Malformations: 3-Dimensional
      Operative Video.
AB  - We present 2 illustrative cases of interhemispheric approaches to right sided
      arteriovenous malformations (AVMs). The first patient is a healthy 54-yr-old
      female who presented with left-sided hearing loss and pulsatile tinnitus, and was
      neurologically intact. Imaging demonstrated a right sided interhemispheric AVM,
      fed by the anterior cerebral artery with superficial venous drainage to the
      superior sagittal sinus. The AVM was thought to be asymptomatic and the patient
      chose to have her AVM treated surgically to eliminate future risk of hemorrhage.
      We elected to approach this lesion via a contralateral interhemispheric approach
      to avoid retraction of the right hemisphere. Intraoperative angiogram
      demonstrated complete obliteration of the malformation and the patient was
      neurologically intact postoperatively. The second patient is a 41-yr-old healthy
      male who presented with progressive bifrontal headaches and was also
      neurologically intact. Imaging revealed a right interhemispheric AVM fed by the
      anterior cerebral artery and with superficial venous drainage to the superior
      sagittal sinus. Although the patient's headaches may have been related, the
      patient's decision to undergo surgical resection was primarily to eliminate
      future risk of hemorrhage. The difference with this patient was that imaging
      revealed the presence of two draining veins on the left side that would
      potentially be injured via a contralateral approach. As a result, we elected to
      approach this lesion ipsilaterally. Intraoperative angiogram showed complete
      obliteration of the malformation with intact venous drainage, and the patient was
      neurologically intact postoperatively. Contralateral vs ipsilateral
      interhemispheric approaches are compared and contrasted.

PMID- 30099563
TI  - Side-to-Side Anastomosis Training Model Using Rat Common Carotid Arteries.
AB  - BACKGROUND: The side-to-side anastomosis is one of the difficult bypass
      configurations that may be used in various complex cerebral vascular and
      neoplastic cases. Few pure arterial models exist for practicing this bypass
      subtype. OBJECTIVE: To provide an optimized side-to-side anastomosis training
      model using rat common carotid arteries (CCA). METHODS: Bilateral CCAs were
      exposed in the neck of 10 anesthetized Sprague-Dawley rats. The arteries were
      juxtaposed in parallel, using temporary aneurysm clips applied proximally and
      distally. CCA caliber and the length of CCA juxtaposition were measured. Side-to
      side anastomosis was completed and ischemia time was recorded. Unintended
      complications were recorded for further analysis. RESULTS: Anastomosis was
      completed successfully in all animals. The CCAs were approximated in all animals
      without any difficulty or undue tension. In 2 rats, death occurred prior to
      completion of anastomosis, which was attributed to injury to the external jugular
      vein during vessel exposure. Mean ischemia time was 35 min with an average of 22
      sutures done to complete the anastomosis. The average CCA caliber was 1.1 +/- 0.2
      mm and the arteries could be juxtaposed for an average length of 10.2 +/- 1.5 mm.
      CONCLUSION: Full exposure of the cervical segment of the CCAs enables tension
      free approximation of adequate length of the vessel for a side-to-side
      anastomosis. Avoiding complications during exposure helps in prevention of animal
      death during the ischemia period.

PMID- 30099564
TI  - Lumbar Arthroplasty Core Herniation Presenting With Cauda Equina Syndrome: Case
      Report of a Rare Complication.
AB  - BACKGROUND: Treatment failures of artificial disc implantation are well
      described, but posterior herniation of the arthroplasty core is rare. We present
      a case of posterior herniation of the arthroplasty core resulting in cauda equina
      syndrome in a 36-yr-old woman. Preoperative imaging studies including computed
      tomography (CT), magnetic resonance imaging (MRI), and CT Myelogram were
      performed; only the CT Myelogram demonstrated the severe compression well. This
      report highlights the radiographic findings on multiple imaging modalities,
      clinical implications, and management considerations of posterior arthroplasty
      failures. OBJECTIVE: To demonstrate a rare complication of lumbar arthroplasties.
      The biomechanical considerations, surgical management, and thorough radiographic
      work-up demonstrate successful diagnosis and treatment of this unusual
      complication. METHODS: The patient's chart was reviewed for medical history,
      laboratory and radiographic studies, and outpatient clinical follow-up. RESULTS:
      After imaging work-up, this patient was found to have a herniation of the
      arthroplasty core at L5-S1. She was taken emergently to the operating room for a
      decompression at L5-S1 and arthroplasty core removal. She made some recovery
      neurological, but over 3 mo time, she developed a spondylolisthesis with new back
      pain and radiculopathy. This ultimately responded well to an L5-S1 instrumented
      posterior fusion. CONCLUSION: Posterior herniation of the lumbar arthroplasty
      core is a rare complication from implantation of an artificial lumbar disc.
      Confirmation of the diagnosis is best confirmed with a CT Myelogram. Furthermore,
      this case underscores the biomechanical importance of the artificial disc given
      the development of the spondylolisthesis after removal, and fusion after
      arthroplasty core removal should be considered.

PMID- 30099565
TI  - Fluorescent "keep-on" type pharmacophore obtained from dynamic combinatorial
      library of Schiff bases.
AB  - We established a novel principle for fluorescence detection of a target protein.
      A low-molecular-weight fluorescent pharmacophore, as a targeted probe, was
      selected from a dynamic combinatorial library of Schiff bases. The pharmacophore
      retains its fluorescence when bound to the hydrophobic site of the target,
      whereas it loses it because of hydrolysis when unbound. Graphical abstract We
      describe a novel concept for detection of a target protein (i.e., HSA) by using a
      keep-on-type fluorescent pharmacophore which is discovered from a dynamic
      combinatorial library of Schiff bases. When the target is absent, the keep-on
      pharmacophore is degraded by hydrolysis, with the result that we can see no
      fluorescence.

PMID- 30099566
TI  - Lack of uniformity among United States recommendations for diagnosis and
      management of acute, uncomplicated cystitis.
AB  - INTRODUCTION AND HYPOTHESIS: Acute, uncomplicated cystitis is one of the most
      common bacterial infections seen in clinical practice. Quality improvement and
      antibiotic stewardship efforts to optimize cystitis management rely on clinicians
      managing patients in a manner recommended by experts and guidelines. However, it
      is unclear if recent recommendations for cystitis from experts and guidelines
      from US medical societies that provide recommendations are well aligned. METHODS:
      We examined recommendations and guidelines for acute, symptomatic cystitis in
      women published in US medical societies' journals from January 1, 2008, to
      December 31, 2016, within the fields of family medicine, obstetrics and
      gynecology, internal medicine, female pelvic medicine and reconstructive surgery,
      and infectious diseases. RESULTS: All recommendations endorsed the use of
      symptoms and urine dipstick to diagnose cystitis. Some societies did not
      recommend urine dipstick in patients with recurrent urinary tract infection
      (UTI), classic UTI symptoms, or a lack of underlying conditions or competing
      diagnoses. All endorsed nitrofurantoin, trimethoprim-sulfamethoxazole, and
      fosfomycin as first-line agents. Some guidelines classified fluoroquinolones as
      second- or third-line, while others considered them first-line treatment for UTI.
      Avoiding use of amoxicillin and ampicillin, antibiotic agents with high
      prevalence of resistance in the US, was recommended by some societies.
      CONCLUSIONS: US recommendations differed in their approach to the treatment of
      acute, uncomplicated cystitis. Lack of uniformity likely contributes to clinical
      management variance for patients with UTI and hampers quality improvement and
      antibiotic stewardship efforts aimed at promoting optimal management. Our
      findings emphasize the need for more consistent recommendations for cystitis
      management.

PMID- 30099567
TI  - Total laparoscopic hysterectomy: how does training for surgeons in a standardized
      operation affect hospitals and patients?
AB  - PURPOSE: Surgical training usually means inexperienced physicians initially doing
      operations supervised by an experienced physician, to gain the experience and
      skills needed to conduct surgery independently. Various issues arise here for
      both hospitals and patients. Are training procedures associated with higher
      complication rates, blood losses, and transfusion rates? What does training in
      the operating room ultimately cost in terms of valuable surgical time? Do longer
      hospitalization periods potentially mean financial losses for the hospital under
      the diagnosis-related groups (DRG) system? METHODS: A retrospective analysis was
      carried out of data for 571 patients who underwent total laparoscopic
      hysterectomy (TLH) in the Department of Gynecology at the University of Erlangen
      from 2009 to 2012, with/without adnexectomy, due to benign indication; and of
      data for 255 patients who underwent the same procedures in Karlsruhe Municipal
      Hospital in 2013-2014. The patients were classified into two groups: those in
      whom surgery was carried out by experienced specialists who had carried out at
      least 40 independent operations; and those in whom it was carried out by a
      trainee resident who had personally done fewer than 40 operations. RESULTS: In
      the two groups, the patients had similar mean body mass indexes, uterus weights,
      and blood losses. Patients in the specialist group were slightly older. There
      were no differences in complication rates. Over two-thirds of complications
      occurred in patients with previous surgery. Procedures by residents took
      significantly longer. Hospitalization periods in both groups were still below the
      mean threshold length of stay under Germany's DRG system, so that no income
      losses occurred even with training procedures. CONCLUSIONS: Training and teaching
      operations supervised by experienced surgeons are just as safe as operations by
      experienced surgeons themselves. Interpretation of these data is of course
      limited by the retrospective study design; patients treated by specialists tended
      to have more prior operations and were older, with a trend toward larger uteri.
      Surgical training, as the example of TLH in benign indication shows here,
      involves an additional time of approximately 10-20 min per operation. With regard
      to the revenue situation, the hospitalization periods in both groups were within
      the profit zone for the hospital concerned.

PMID- 30099569
TI  - Stability analysis of a steady state of a model describing Alzheimer's disease
      and interactions with prion proteins.
AB  - Alzheimer's disease (AD) is a neuro-degenerative disease affecting more than 46
      million people worldwide in 2015. AD is in part caused by the accumulation of
      A[Formula: see text] peptides inside the brain. These can aggregate to form
      insoluble oligomers or fibrils. Oligomers have the capacity to interact with
      neurons via membrane receptors such as prion proteins ([Formula: see text]). This
      interaction leads [Formula: see text] to be misfolded in oligomeric prion
      proteins ([Formula: see text]), transmitting a death signal to neurons. In the
      present work, we aim to describe the dynamics of A[Formula: see text] assemblies
      and the accumulation of toxic oligomeric species in the brain, by bringing
      together the fibrillation pathway of A[Formula: see text] peptides in one hand,
      and in the other hand A[Formula: see text] oligomerization process and their
      interaction with cellular prions, which has been reported to be involved in a
      cell-death signal transduction. The model is based on Becker-Doring equations for
      the polymerization process, with delayed differential equations accounting for
      structural rearrangement of the different reactants. We analyse the well
      posedness of the model and show existence, uniqueness and non-negativity of
      solutions. Moreover, we demonstrate that this model admits a non-trivial steady
      state, which is found to be globally stable thanks to a Lyapunov function. We
      finally present numerical simulations and discuss the impact of model parameters
      on the whole dynamics, which could constitute the main targets for pharmaceutical
      industry.

PMID- 30099568
TI  - Novel synthetic 4-chlorobenzoyl berbamine inhibits c-Myc expression and induces
      apoptosis of diffuse large B cell lymphoma cells.
AB  - C-Myc expression is associated with poor prognosis and aggressive progression of
      diffuse large B cell lymphoma (DLBCL), and the development of drug-like c-Myc
      inhibitors remains challenging. In this study, we report a novel berbamine
      derivative termed 4-chlorobenzoyl berbamine (CBBM) that potently induced the
      apoptosis of c-Myc-overexpressing DLBCL cells but spared normal blood cells. The
      compound showed IC50 values ranging from 1.93 to 3.89 MUmol/L in DLCBL cells and
      exhibited a 4.75- to 9.64-fold increase in anti-tumor activity compared to
      berbamine. Additionally, CBBM inhibited the proliferation of the DLBCL line OCI
      Ly3 cells through G0/G1 cell-cycle arrest and induced apoptosis. Further studies
      have shown that CBBM treatment leads to the proteasome-dependent degradation of c
      Myc protein in OCI-Ly3 cells. Interestingly, we found that the inhibitory effect
      of CBBM was positively correlated with basal levels of CaMKIIgamma, which is a
      key inducer of c-Myc expression in DLBCL cells. We also observed that CBBM
      inhibits the JAK2/STAT3 pathway, leading to reduced c-Myc transcription.
      Collectively, these findings suggest that CBBM could be a promising lead compound
      for treatment of c-Myc-driven DLBCL.

PMID- 30099570
TI  - Meniscal fixation is a successful treatment for hypermobile lateral meniscus in
      soccer players.
AB  - PURPOSE: To report the outcomes (subjective function, return to play,
      complications and reoperations) of arthroscopic all-inside meniscal fixation in a
      large sample of soccer players with hypermobile lateral meniscus. METHODS:
      Between 2010 and 2015, 55 patients undergoing surgical treatment for hypermobile
      lateral meniscus at Mutualidad Catalana de Futbolistas (Barcelona, Spain) were
      identified. Patients with open physes, associated injuries, discoid meniscus, or
      clinical follow-up less than 6 months were excluded. Once identified, all
      patients were contacted over the phone to collect cross-sectional data on
      International Knee Documentation Committee (IKDC) score, postoperative Tegner
      score, and postoperative visual analogue scale (VAS) for pain. In addition,
      complications and reoperations were retrospectively collected. RESULTS: Forty-six
      cases (in 45 patients) with a mean (SD) age of 26.3 (9.5) years and mean (SD;
      range) follow-up of 43 (19.5; 8-73) months were included. The pre- and post
      operative median (range) Tegner score was 9 (6-9) and 8 (0-9), respectively.
      Compared to the preoperative period, the postoperative Tegner score was equal in
      27/46 (59%) cases and lower in 16/46 (35%) cases (3 missing values). Return to
      play was possible in 38/46 (82%) cases, from which 27/46 (59%) corresponded to
      the same pre-injury activity level. Postoperatively, the median (range) VAS for
      pain was 1 (0-9), and the mean (SD) subjective IKDC was 86.2 (16.7). Three of the
      46 cases (6.5%) required a reoperation because of pain in one patient (meniscal
      suture failure) and meniscal tear in two patients. CONCLUSIONS: All-inside
      meniscal fixation is a successful treatment for hypermobile lateral meniscus,
      which allows acceptable return to play and good function in soccer players at a
      low reoperation rate. However, according to the present cross-sectional case
      series, players should be advised that return to the same pre-injury activity
      level is achieved in only 27 of 46 (59%) of the cases. Surgeons facing with the
      difficult problem of hypermobile lateral meniscus in soccer players should
      consider meniscus fixation as an easy and successful option. LEVEL OF EVIDENCE:
      Level IV-Therapeutic Case Series.

PMID- 30099571
TI  - Plant cell culture technology in the cosmetics and food industries: current state
      and future trends.
AB  - The production of drugs, cosmetics, and food which are derived from plant cell
      and tissue cultures has a long tradition. The emerging trend of manufacturing
      cosmetics and food products in a natural and sustainable manner has brought a new
      wave in plant cell culture technology over the past 10 years. More than 50
      products based on extracts from plant cell cultures have made their way into the
      cosmetics industry during this time, whereby the majority is produced with plant
      cell suspension cultures. In addition, the first plant cell culture-based food
      supplement ingredients, such as Echigena Plus and Teoside 10, are now produced at
      production scale. In this mini review, we discuss the reasons for and the
      characteristics as well as the challenges of plant cell culture-based productions
      for the cosmetics and food industries. It focuses on the current state of the art
      in this field. In addition, two examples of the latest developments in plant cell
      culture-based food production are presented, that is, superfood which boosts
      health and food that can be produced in the lab or at home.

PMID- 30099572
TI  - Temporal dynamics of activated sludge bacterial communities in two diversity
      variant full-scale sewage treatment plants.
AB  - Bacterial community in activated sludge (AS) is diverse and highly dynamic.
      Little is known about the mechanism shaping bacterial community composition and
      dynamics of AS and no study had quantitatively compared the contribution of
      abiotic environmental factors and biotic associations to the temporal dynamics of
      AS microbial communities with significantly different diversity. In this study,
      two full-scale sewage treatment plants (STPs) with distinct operational
      parameters and influent composition were sampled biweekly over 1 year to reveal
      the correlating factors to whole and sub-groups of AS bacterial community
      diversity and dynamics. The results show that the bacterial communities of the
      two STPs were entirely different and correlated with the influent composition and
      operating configurations. Bacterial associations represented by cohesion metrics
      and the environmental factor temperature were the primary correlated factors to
      the temporal bacterial community dynamics within each STP. The STP with high
      diversity and evenness could treat influent with higher suspended solid and a
      shorter sludge retention time, and was less correlated with environmental
      factors, implying the importance of diversity for AS system.

PMID- 30099573
TI  - Not all drugs are created equal: impaired future thinking in opiate, but not
      alcohol, users.
AB  - Episodic future thinking refers to the ability to travel forward in time to pre
      experience an event. Although future thinking has been intimately linked with
      self and identity, to our knowledge, no prior research has compared episodic
      future thinking in populations with different substance use disorders. This study
      investigates whether there are differences in episodic future thinking between
      these alcohol and opiate users. The study recruited participants who were on the
      opiate substitution program (n = 31) and individuals who had been diagnosed with
      alcohol dependence (n = 21) from the Royal Prince Alfred Hospital Drug and Health
      Services. Healthy controls (n = 23) were recruited via Royal Prince Alfred
      Hospital databases and the general community. Past and future thinking was
      measured using four cue words. After each cue word, participants rated their
      phenomenological experience (e.g. emotion, reliving experience). Results
      indicated that alcohol-dependent individuals performed significantly higher in
      episodic future thinking compared to opiate users. These findings indicate that
      not all substance use disorder groups share similar episodic thinking
      capabilities. Our results suggest that the self-projection component of
      rehabilitation programs may have to be tailored to the different episodic
      construction abilities found in substance use disorder groups.

PMID- 30099574
TI  - Different Trypanosoma cruzi calreticulin domains mediate migration and
      proliferation of fibroblasts in vitro and skin wound healing in vivo.
AB  - Calreticulin is an endoplasmic reticulum-resident, calcium-binding, stress
      produced, chaperone protein that serves multiple functions and is widely
      distributed in eukaryotic cells. Exogenously applied recombinant calreticulin
      solution, markedly enhanced the rate and quality of skin wound healing. These
      modulatory effects are more efficient than commercially available topic platelet
      derived growth factor ointments (Regranex(r)). Trypanosoma cruzi calreticulin is
      more effective in equimolar terms to human counterpart in accelerating skin wound
      healing. While the effect of externally added recombinant parasite calreticulin
      on wound healing has been reported, the domains responsible for these modulatory
      effects have not yet been established. Here, recombinant parasite calreticulin
      and some of its domains were tested to assess their influence in increasing
      proliferation and migration of fibroblasts in vitro and rat skin wound healing in
      vivo. Herein, we propose that Trypanosoma cruzi whole calreticulin or some of its
      domains are differentially involved in the modulation of wound-healing cell
      migration and proliferation, and cosmetic outcome. Therefore, precise combination
      of the parasite protein and its domains could allow us to tailor-specific desired
      effects during the skin wound-healing process.

PMID- 30099576
TI  - Relationships between Hoffa fragment size and surgical approach selection: a
      cadaveric study.
AB  - INTRODUCTION: Fixation of a small Hoffa fragment requires a selection of the
      proper surgical approach for reduction and posterior to anterior screws fixation.
      However, currently there are no guidelines regarding how to select the best
      approach for small posterior Hoffa fractures. OBJECTIVES: To compare the size of
      Hoffa fractures that are appropriate for reduction and fixation with the medial
      parapatellar approach (MPPA) and those which require the direct medial approach
      (DMA), and to make a similar comparison between the lateral parapatellar approach
      (LPPA) and the posterolateral approach (PLA). MATERIALS AND METHODS: Twenty
      extremities of fresh cadavers were included. After completion of each approach,
      the articular surface boundaries were marked and soft tissue was removed. On the
      medial condyle, an imaginary line was drawn from the most anterior (A) to the
      most posterior (B) point, representing the AP diameter (d3). The most posterior
      boundary of MPPA (C) and the most anterior boundary of DMA (D) were similarly
      marked. Distances between B and C (d1) and between B and D (d2) were measured as
      well as the anterior-posterior diameter of the condyle (d3). The same
      measurements were made for the lateral condyle. RESULTS: On the medial condyle,
      the average values of d1, d2, and d3 were 10.8 mm +/- 3.8, 17.3 mm +/- 3.3, and
      60.1 mm +/- 3.2, while percentages of d1/d3 and d2/d3 were 18.3% +/- 6.4 and
      28.7% +/- 4.7. In lateral condyle, the averages for d1, d2, d3 were 6.1 mm +/-
      1.4, 12.1 mm +/- 2.8 and 60.9 mm +/- 3.3 mm and the percentages of d1/d3 and
      d2/d3 were 10.1% +/- 2.3 and 19.9% +/- 4.9. CONCLUSIONS: When the Hoffa fragment
      is less than 18.3% of the AP diameter of medial condyle or 10.1% of lateral
      condyle, the fracture is invisible with the PPA. When the Hoffa fragment is more
      than 28.7% of the medial condyle or 19.9% of the lateral condyle, the PPA should
      be selected. If the Hoffa fragment is less than 28.7% of the medial condyle or
      19.9% of the lateral condyle, the DMA or PLA with posterior-to-anterior screws is
      recommended. Combined approaches should be considered in some complex cases with
      articular comminution.

PMID- 30099575
TI  - Long-term results of revision total hip arthroplasty with a cemented femoral
      component.
AB  - INTRODUCTION: In revision total hip arthroplasty (THA), the cancellous bone is
      normally completely removed out of the femoral canal during stem extraction. This
      situation is comparable to primary THA following the shape-closed concept, with
      some authors advocating to remove the metaphyseal cancellous bone to enhance
      press-fit stability ("French paradox"). The aim of this study was to investigate
      the long-term outcome, regarding survival and radiological results, of a cemented
      straight stem when used for revision THA and to compare these results to the
      results of the same stem in primary THA. MATERIALS AND METHODS: 178 stem
      revisions performed between 01/1994 and 08/2008 using the Virtec straight stem
      were included. The cumulative incidence for re-revision was calculated using a
      competing risk model. Risk factors for re-revision of the stem were analyzed
      using an absolute risk regression model. Radiographs analyzed for osteolysis,
      debonding and subsidence had a minimum follow-up of 10 years. RESULTS: The
      cumulative incidence for re-revision due to aseptic loosening of the stem was
      5.5% (95% CI, 2.9-10.2%) at 10 years. Aseptic loosening was associated with
      younger age, larger defect size and larger stem size. After a minimum 10-year
      follow-up, osteolysis was seen in 39 of 80 revision THA. Compared to the results
      in primary THA, the survival in revision THA with the same implant was inferior.
      CONCLUSIONS: Cemented straight stems used for revision THA showed excellent long
      term results regarding survivorship and radiological outcome. This stem therefore
      offers a valuable and cost-effective option in revision THA.

PMID- 30099577
TI  - Radiochemotherapy-induced reactivation of scar tissue on 18F-FDG PET/CT.

PMID- 30099579
TI  - Wake-up call for more doctor-patient communication and an increase in public
      information campaigns on the risk factor of smoking with regard to the
      development and prognosis of bladder cancer.

PMID- 30099580
TI  - Genomics and clinical correlates of renal cell carcinoma.
AB  - PURPOSE: Clear cell, papillary cell, and chromophobe renal cell carcinomas (RCCs)
      have now been well characterised thanks to large collaborative projects such as
      The Cancer Genome Atlas (TCGA). Not only has knowledge of the genomic landscape
      helped inform the development of new drugs, it also promises to fine tune
      prognostication. METHODS: A literature review was performed summarising the
      current knowledge on the genetic basis of RCC. RESULTS: The Von Hippel-Lindau
      (VHL) tumour suppressor gene undergoes bi-allelic knockout in the vast majority
      of clear cell RCCs. The next most prevalent aberrations include a cohort of
      chromatin-modifying genes with diverse roles including PBRM1, SETD2, BAP1, and
      KMD5C. The most common non-clear cell renal cancers have also undergone genomic
      profiling and are characterised by distinct genomic landscapes. Many recurrent
      mutations have prognostic value and show promise in aiding decisions regarding
      treatment stratification. Intra-tumour heterogeneity appears to hamper the
      clinical applicability of sparsely sampled tumours. Ways to abrogate
      heterogeneity will be required to optimise the genomic classification of tumours.
      CONCLUSION: The somatic mutational landscape of the more common renal cancers is
      well known. Correlation with outcome needs to be more comprehensively furnished,
      particularly for small renal masses, rarer non-clear cell renal cancers, and for
      all tumours undergoing targeted therapy.

PMID- 30099578
TI  - 18F-FDGPET/CT in fever of unknown origin and inflammation of unknown origin: a
      Chinese multi-center study.
AB  - PURPOSE: To evaluate the clinical value of 18F-FDG-PET/CT for the diagnosis of
      fever of unknown origin (FUO) and inflammation of unknown origin (IUO) in Chinese
      population, as well as the characteristics of PET/CT in different category of
      etiological disease. METHODS: A total of 376 consecutive patients with FUO/IUO
      who underwent FDG-PET/CT at 12 hospitals were retrospectively studied. FDG uptake
      was quantitatively and visually evaluated, by using SUVmax and a 4-grade scale
      respectively. A questionnaire survey to the clinicians was used to evaluate the
      significance of PET/CT in diagnosing of FUO/IUO. Data analysis included the
      etiological distribution in the study population, image characteristics in
      different category of diseases, and clinical significance of PET/CT. RESULTS: In
      376 studied patients, the infectious diseases accounted for 33.0% of patients,
      rheumatologic diseases for 32.4%, malignancies for 19.1%, miscellaneous causes
      for 6.6%, and cause unknown for 8.8%. However, the etiological distribution among
      hospitals was varied. In addition, the etiological disease composition ratio has
      changed over time in China. On PET/CT examinations, 358 (95.2%) of the patients
      had a positive finding. Within them, local high uptake lesion was found in 219
      cases, and nonspecific abnormal uptake (NAU) was found in 187 cases. FDG uptake
      in malignant diseases was significantly higher than in other category diseases
      both on SUVmax and visual scores (t-value range from 4.098 to 5.612, all P value
      < 0.001). Based on a clinical questionnaire survey, PET/CT provided additional
      diagnostic information for 77.4% of patients, and 89.6% of patients benefited
      from PET/CT examination. CONCLUSIONS: FDG PET/CT is a valuable tool for clinical
      diagnosis of FUO/IUO, and it is of great significance in further investigating
      the usefulness of PET/CT in non-neoplastic diseases.

PMID- 30099581
TI  - Pitfalls in the management of congenital tracheal stenosis: is conservative
      management feasible?
AB  - PURPOSE: Congenital tracheal stenosis (CTS) is rare and challenging. Complete
      tracheal rings cause a wide spectrum of airway-obstructing lesions and varying
      degrees of respiratory distress. Although surgical reconstruction is the primary
      option for symptomatic CTS, sometimes an appropriate management strategy may be
      difficult due to other anomalies. We aimed to identify pitfalls in the management
      of CTS. METHODS: We retrospectively reviewed the records of patients with CTS
      during the last 10 years in our institution. RESULTS: Sixteen pediatric patients
      were diagnosed with CTS. Of the 16 patients, 12 (75.0%) had cardiovascular
      anomalies including seven left pulmonary artery sling. Six patients with dyspnoea
      caused by CTS and three patients with difficult intubations due to CTS underwent
      tracheoplasty. Four patients underwent only cardiovascular surgery without
      tracheoplasty. Three asymptomatic patients were followed up without undergoing
      any surgical procedure. We repeatedly discussed management of four patients with
      especially complex pathophysiology at multidisciplinary meetings. Right
      ventricular outflow tract obstruction, tracheobronchial malacia, increased
      pulmonary blood flow, and pulmonary aspiration due to gastroesophageal reflux
      presumably accounted for their severe respiratory distress, and we forewent their
      tracheal reconstruction. CONCLUSION: The management of CTS should be
      individualized, and conservative management is a feasible option in selected
      cases.

PMID- 30099582
TI  - New prognostic classification and managements in infants with esophageal atresia.
AB  - PURPOSE: The aim of this study was to investigate the risk factors for in
      hospital mortality in infants with esophageal atresia (EA) without critical
      chromosome abnormality disorders and develop a new prognostic classification to
      assess the influence of external risk factors on the prognosis of EA, which could
      provide more effective treatment strategies in clinical practice. METHODS: A
      retrospective chart review of all consecutive patients between January 1994 and
      December 2017, which included 65 EA infants who were admitted to Shizuoka
      Children's Hospital, was conducted. Based on multivariate analysis data and ROC
      analysis, the discrimination of the new prognostic classification was quantified
      and compared with that of the Spitz classification using the area under the ROC
      curve (AUC). RESULTS: Multiple logistic regression analysis showed that birth
      weight of < 1606 g (adjusted OR, 13.16; 95% CI, 1.16-352.75), and complex cardiac
      anomalies (adjusted OR 22.39; 95% CI 2.45-569.14) were significant risk factors
      for death. We have created a new classification close to Spitz classification
      using the presence of complex cardiac anomalies and birth weight. The mortality
      rates were 0% for class I (n = 0/40), 7.1% for class II (n = 1/14), 33.3% for
      class III (n = 3/9), and 100% for class IV (n = 2/2). The AUC of the new
      classification was better than that of the Spitz classification (0.939 vs 0.812,
      respectively; p = 0.04). CONCLUSION: New prognostic classification can improve
      the stratification of EA patients and be a useful predictor of survival.

PMID- 30099583
TI  - Improving the knowledge and behavior of workplace chemical exposures in
      Vietnamese-American nail salon workers: a randomized controlled trial.
AB  - OBJECTIVES: We assessed the efficacy of trainings with Vietnamese nail salon
      owners and workers on knowledge and behaviors that could reduce exposures to
      toxic chemicals in nail products. METHODS: We trained Vietnamese salon owners in
      California (n = 77) who then trained their workers (n = 200) on best practices.
      In a cluster randomized controlled trial, we assessed the efficacy of the
      training on change in knowledge and self-reported behaviors. Data were collected
      from 2013 to 2016 and analyzed from 2016 to 2017. RESULTS: Compared to the
      control group, the intervention group had significantly greater increases in
      knowledge about: safer nail polishes [odds ratio (OR) 3.7 (95% confidence
      interval (CI) 1.9, 7.2)]; proper ventilation methods (OR 4.2; 95% CI 2.2, 8.1);
      recommended glove types (OR 3.4; 95% CI 1.9, 6.3); and recommended product
      handling and storage (OR 4.1; 95% CI 1.7, 9.9). The intervention also increased
      best practices: using safer nail polishes (OR 3.6; 95% CI 1.9, 6.8); reading
      product labels (OR 2.6; 95% CI 1.3, 5.0); and wearing long sleeves (OR 2.4; 95%
      CI 1.3, 4.2). CONCLUSIONS: The owner-to-worker intervention with culturally and
      linguistically appropriate training for salon owners who then trained workers was
      effective in promoting knowledge and self-reported behaviors that can reduce
      workplace chemical exposures.

PMID- 30099584
TI  - Risk Stratification in Patients with Complicated Parapneumonic Effusions and
      Empyema Using the RAPID Score.
AB  - PURPOSE: Complicated parapneumonic effusions and empyema are a leading cause of
      morbidity in the United States with over 1 million admissions annually and a
      mortality rate that remains high in spite of recent advances in diagnosis and
      treatment. The identification of high risk patients is crucial for improved
      management and the provision of cost-effective care. The RAPID score is a scoring
      system comprised of the following variables: renal function, age, purulence,
      infection source, and dietary factors and has been shown to predict outcomes in
      patients with pleural space infections. METHODS: In a single center retrospective
      study, we evaluated 98 patients with complicated parapneumonic effusions and
      empyema who had tube thoracostomy (with or without Intrapleural fibrinolytic
      therapy) and assessed treatment success rates, mortality, length of hospital
      stay, and direct hospitalization costs stratified by three RAPID score
      categories: low-risk (0-2), medium risk (3-4), and high-risk (5-7) groups.
      RESULTS: Treatment success rate was 71%, and the 90 day mortality rate was 12%.
      There was a positive-graded association between the low, medium and high RAPID
      score categories and mortality, (5.3%, 8.3% and 22.6%, respectively), length of
      hospital stay (10, 21, 19 days, respectively), and direct hospitalization costs
      ($19,909, $36,317 and $43,384, respectively). CONCLUSION: Our findings suggest
      that the RAPID score is a robust tool which could be used to identify patients
      with complicated parapneumonic effusions and empyema who may be at an increased
      risk of mortality, prolonged hospitalization, and who may incur a higher cost of
      treatment. Randomized controlled trials identifying the most effective initial
      treatment modality for medium- and high-risk patients are needed.

PMID- 30099585
TI  - Fatigue in patients with myasthenia gravis.
AB  - BACKGROUND: The subjective feeling of fatigue in myasthenia gravis (MG) is poorly
      elucidated, in part because it is often confounded with the objective sign of
      muscle fatigability. Another reason is the paucity of validated fatigue
      questionnaires in MG. METHODS: We applied the 9-item Fatigue Severity Scale (FSS)
      and the 40-item Fatigue Impact Scale (FIS) to 73 MG patients and 230 age- and sex
      matched control subjects. We ascertained levels of education, marital status, and
      comorbidities such as depression, sleepiness, sleep times and sleep debt. Disease
      severity was graded according to the Myasthenia Gravis Foundation of America
      (MGFA) classification. RESULTS: All fatigue scores, with the exception of the
      cognitive FIS subscale, were higher in MG patients than controls. In MG, the
      prevalence of fatigue (defined by FSS scores >= 4.0) was 70%. Multiple regression
      analyses revealed several independent associates of fatigue, including depression
      (all fatigue scales), MGFA stage (FSS, physical FIS), female sex (cognitive and
      psychosocial FIS), and sleep debt (physical FIS). CONCLUSION: Fatigue in MG is
      highly prevalent, mainly physical, and influenced by depressive symptoms, disease
      severity, female sex and sleep debt. Cognitive fatigue in MG may not be a direct
      disease manifestation, but secondary to depression. The FSS and FIS represent
      reliable and validated tools, appropriate to discern meaningful clinical aspects
      of fatigue in MG. Clinical recognition of the complexity of fatigue may foster
      individualized treatment approaches for affected MG patients.

PMID- 30099589
TI  - Optimizing stimulus waveforms for electroceuticals.
AB  - There has been a growing interest in the use of electrical stimulation as a
      therapy across diverse medical conditions. Most electroceutical devices use
      simple waveforms, for example sinusoidal or rectangular biphasic pulses.
      Clinicians empirically tune the waveform parameters (e.g. amplitude, frequency)
      without altering the fundamental shape of the stimulus. In this article, we
      review computational strategies that have been used to optimize the shape of
      stimulus waveforms in order to improve clinical outcomes, and we discuss
      potential directions for future exploration.

PMID- 30099588
TI  - Age estimation combining radiographic information of two dental and four skeletal
      predictors in children and subadults.
AB  - Improved age estimates may result from combining different age predictors. This
      study aimed to validate age estimation performances combining the radiographic
      development of teeth, cervical vertebrae, hand and wrist bones, skull, and
      mandible. The sampled consisted of 256 individuals aged between 4 and 20 years.
      Bayes' rule with a multivariate continuation ratio model was applied for the
      distribution of the dental scores. The additional age information of the skeletal
      variables was assessed extending the dental model separately and combining the
      variables. The performances of all models were quantified and compared using mean
      error (ME), mean absolute error (MAE), and root mean squared error (RMSE). The
      best performance resulted combining all variables (ME - 0.04 for F and M; MAE
      0.91 for F and 0.95 for M; RMSE 1.14 for F and 1.19 for M). To improve
      performances and minimize radiation doses, the combination of teeth and hand and
      wrist bones information is recommended.

PMID- 30099587
TI  - Nuclear loss and cytoplasmic expression of androgen receptor in penile
      carcinomas: role as a driver event and as a prognosis factor.
AB  - Androgen receptor (AR) is a member of the steroid and nuclear family receptor
      that acts as transcription factor. AR signaling plays pivotal role in the
      development and progression of prostate cancer. However, the role of AR in penile
      cancer (PeCa) is poorly explored. Our previous molecular studies unveiled
      frequent AR mRNA loss in PeCa, which was further predicted as a major driver
      alteration in this neoplasm. Herein, we assessed the AR protein expression in 59
      usual PeCa tissues and 42 surrounding normal tissues (SNT) by
      immunohistochemistry using a tissue microarray. In a paired analysis, we found a
      total absence of nuclear AR expression in PeCa while 95.2% of SNT samples
      presented strong nuclear AR expression (P < 0.001). Interestingly, 17 of 42 PeCa
      presented weak or moderate cytoplasmic AR staining, contrasting with 5 of 42 SNT
      (P = 0.008). Increased levels of AR cytoplasmic expression were related with poor
      prognosis features including advanced clinical staging (P = 0.044), compromised
      surgical margins (P = 0.005), and pathological inguinal node status (P = 0.047).
      Furthermore, AR cytoplasmic expression was also related with shorter overall
      survival (P = 0.032). In conclusion, the frequent loss of nuclear AR protein
      levels suggests a potential function in PeCa development. Based on this result,
      the androgen deprivation therapy is not indicated for PeCa patients. In addition,
      the AR cytoplasmic expression found in a significant number of cases (40.5%)
      showed prognostic value and pathways activated by the non-genomic AR signaling
      may represent a promising therapeutic strategy.

PMID- 30099586
TI  - Biocontrol strain Aspergillus flavus WRRL 1519 has differences in chromosomal
      organization and an increased number of transposon-like elements compared to
      other strains.
AB  - Aflatoxins are toxic secondary metabolites produced by members of the genus
      Aspergillus, most notably A. flavus. Non-aflatoxigenic strains of A. flavus are
      commonly used for biocontrol of the aflatoxigenic strains to reduce aflatoxins in
      corn, cotton, peanuts and tree nuts. However, genomic differences between
      aflatoxigenic strains and non-aflatoxigenic strains have not been reported in
      detail, though such differences may further elucidate the evolutionary histories
      of certain biocontrol strains and help guide development of other useful strains.
      We recently reported the genome and transcriptome sequencing of A. flavus WRRL
      1519, a strain isolated from almond that does not produce aflatoxins or
      cyclopiazonic acid due to deletions in the biosynthetic gene clusters. Continued
      bioinformatics analyses focused on comparing strain WRRL 1519 to the
      aflatoxigenic strain NRRL 3357. The genome assembly of strain WRRL 1519 was
      improved by anchoring 84 of the 127 scaffolds to the putative nuclear chromosomes
      of strain NRRL 3357. The five largest areas of extrachromosomal mismatches
      observed between WRRL 1519 and NRRL 3357 were not similar to any of the
      mismatches that were observed with pairwise comparisons of NRRL 3357 to other non
      aflatoxigenic strains NRRL 21882, NRRL 30797 or NRRL 18543. Comparisons of
      predicted secondary metabolite gene clusters uncovered two other biosynthetic
      gene clusters in which strain WRRL 1519 had large deletions compared to the
      homologous clusters in NRRL 3357. Additionally, there was a marked
      overrepresentation of repetitive sequences in WRRL 1519 compared to other
      inspected A. flavus strains. This is the first report of detection of a large
      number of putative retrotransposons in any A. flavus strain, initially suggesting
      that retrotransposons may contribute to the natural occurrence of genetic
      variation and biocontrol strains. However, the transposons may not be
      significantly associated with the chromosomal differences. Future experimentation
      and continued bioinformatics analyses will potentially illuminate causes of the
      differences and may reveal whether transposon activity in A. flavus can lead to
      random natural occurrences of non-aflatoxigenic strains.

PMID- 30099590
TI  - Cotranscriptional 3'-End Processing of T7 RNA Polymerase Transcripts by a Smaller
      HDV Ribozyme.
AB  - In vitro run-off transcription by T7 RNA polymerase generates heterogeneous 3'
      ends because the enzyme tends to add untemplated adenylates. To generate
      homogeneous 3'-termini, HDV ribozymes have been used widely. Their sequences are
      added to the 3'-terminus such that co-transcriptional self-cleavage generates
      homogeneous 3'-ends. A shorter HDV sequence that cleaves itself efficiently would
      be advantageous. Here we show that a recently discovered, small HDV ribozyme is a
      good alternative to the previously used HDV ribozyme. The new HDV ribozyme is
      more efficient in some sequence contexts, and less efficient in other sequence
      contexts than the previously used HDV ribozyme. The smaller size makes the new
      HDV ribozyme a good alternative for transcript 3'-end processing.

PMID- 30099591
TI  - Ultrasound of sacroiliac joints in spondyloarthritis: a systematic review.
AB  - Ultrasound (US) is an accessible imaging technique with a possible role to
      diagnose active sacroiliitis, so this technique is projected as a promising
      diagnostic tool for the diagnosis of SpA. We analyse the available evidence about
      the use of US as a diagnostic tool in sacroiliitis in patients with SpA, by a
      systemic review of the literature fulfilling OMERACT criteria. A systematic
      literature search for original articles was carried out using four databases
      (Medline, Embase, Scopus and Web of Science). Data from studies were included
      only if participants had SpA and a US examination of sacroiliac joint (SIJ) was
      performed. The methodological quality of the studies was assessed using QUADAS-2
      tool. Thirteen studies were included. All studies were observational, prospective
      and cross-sectional. In most articles (76.9%), the main US finding compatible
      with sacroiliitis evaluated was the presence of vascularisation (Doppler signals)
      with measurements of the resistive index (RI). The sensitivity and specificity
      analysis were performed in seven studies (58.8%) and were good, with a median of
      90 and 89.2%, respectively. The studies showed a positive to moderate a strong
      correlation between the US and the gold standard but this was optimal only in
      four studies. In general, the agreement was good in all studies (>= 0.80). The
      methods of evaluation of sacroiliitis vary between the studies included. To date,
      there is not enough evidence to support the use of ultrasound as a diagnostic
      method for sacroiliitis but it has potential to identify structural lesions at
      SIJ's level.

PMID- 30099592
TI  - A retrospective study comparing the phenotype and outcomes of patients with
      polyarteritis nodosa between UK and Turkish cohorts.
AB  - There is a need for better definition of polyarteritis nodosa (PAN) subphenotypes
      and the influence of ethnicity and geography. This study is aimed to study the
      demographic and clinical features of PAN cohorts from the UK and Turkey (TR) and
      to compare and contrast disease characteristics. A retrospective survey of
      databases from two vasculitis centres between 1990 and 2016 for PAN patients
      fulfilling the EMEA Vasculitis Classification algorithm. All paediatric-onset
      adult patients met the Ankara 2008 (EULAR/PReS endorsed) criteria for childhood
      PAN. Those with typical angiographic and/or histopathologic findings consistent
      with PAN were included. 93 (M/F: 51/42) patients (UK: 47, TR: 46) were included.
      Three were HBV-related, 20 (21.5%) had paediatric onset and 16 (16.5%), cutaneous
      PAN. TR patients had younger age of disease onset 44 (28.5-59.0) vs. 24.5 (11.8
      40.5), p = 0.002. Twelve (26%) of TR patients had monogenic disease (Familial
      Mediterranean Fever association (n = 7), deficiency of adenosine deaminase 2,
      DADA2, (n = 5). No difference was found in phenotype between paediatric and adult
      onset patients except for frequency of cutaneous lesions (p = 0.002). During a
      median 67.5 (32-126) months follow-up, 13 patients died (12.7% in UK vs. 15.2% in
      Turkish cohorts). No difference was found between two cohorts in relation to
      relapse rate, death and vasculitis damage index. This study defined a diagnosis
      of PAN according to the EMEA algorithm. The TR group had a younger age of disease
      onset and more cases of monogenic disease; however, disease extent, relapse rate,
      damage index and death rates were similar between groups.

PMID- 30099594
TI  - Ethynylglycine synthon, a useful precursor for the synthesis of biologically
      active compounds: an update. Part II: synthetic uses of ethynylglycine synthon.
AB  - The ethynylglycine synthon {(R)-2,2-dimethyl-3-(tert-butoxycarbonyl)-4-ethynyl
      oxazolidine} is a chiral compound with valuable synthetic interest. An update
      (covering literature from 2005 to 2017) on the different synthetic utilities is
      reviewed and discussed.

PMID- 30099593
TI  - Lupus anticoagulant hypoprothrombinemia syndrome associated with systemic lupus
      erythematosus in children: report of two cases and systematic review of the
      literature.
AB  - We report two children with systemic lupus erythematosus (SLE) having severe
      bleeding manifestations and lupus anticoagulant hypoprothrombinemia syndrome
      (LAHPS) along with a review of published cases of childhood SLE and LAHPS. We
      report clinical and laboratory profile of two children diagnosed with childhood
      SLE and LAHPS. We also conducted literature search to identify similar published
      cases and a review was performed. An 8-year-old girl had presented with fever,
      arthralgia, alopecia, anasarca and bleeding from multiple sites. She was
      diagnosed to have SLE based on laboratory investigations which showed anemia,
      thrombocytopenia, low complements, positive anti-nuclear antibody (ANA) and
      double standard DNA (dsDNA) antibodies. She was also found to have prolonged
      prothrombin time (PT) and activated partial thromboplastin time (aPTT), positive
      lupus anticoagulant (LA) and low factor II levels. She was diagnosed to have SLE
      with LAHPS and treated with intravenous methylprednisolone, intravenous
      immunoglobulin and cyclophosphamide with good outcome. Patient 2 was a 7-year-old
      boy who was diagnosed to have SLE when he presented with fever, anasarca, malar
      rash, arthritis and bleeding from skin and mucosa. Laboratory investigations
      revealed anemia, proteinuria, low complements, positive ANA and anti-dsDNA titre.
      Coagulation studies showed deranged PT and aPTT, positive LA and low factor II
      levels. He was diagnosed to have SLE with LAHPS and was treated with intravenous
      methylprednisolone and oral mycophenolate mofetil. Review of literature of cases
      with childhood SLE and LAHPS showed that there are 32 cases have been reported
      till date which have been summarized. LAHPS is an uncommonly identified cause of
      bleeding in patients with SLE and must be suspected while evaluating these
      children.

PMID- 30099595
TI  - Membrane affinity and fluorescent labelling: comparative study of monolayer
      interaction, cellular uptake and cytotoxicity profile of carboxyfluorescein
      conjugated cationic peptides.
AB  - Fluorescent labelling is a common approach to reveal the molecular details of
      cellular uptake, internalisation, transport, distribution processes in biological
      systems. The conjugation with a fluorescent moiety might affect relevant physico
      chemical and in vitro transport properties of the bioactive component. A
      representative set of seven cationic peptides-including cell-penetrating peptides
      as well as antimicrobial peptides and synthetic derivatives-was selected for our
      comparative study. Membrane affinity of the peptides and their 5(6)
      carboxyfluorescein (Cf) derivatives was determined quantitatively and compared
      applying Langmuir monolayer of zwitterionic (DPPC) and negatively charged (DPPC +
      DPPG) lipids as cell membrane models. The interaction with neutral lipid layer is
      mainly governed by the overall hydrophobicity of the molecule which is remarkably
      increased by Cf-conjugation for the most hydrophobic Magainin, Melittin and
      Transportan. A significantly enhanced membrane affinity was detected in
      negatively charged lipid model monolayer for all of the peptides since the
      combination of electrostatic and hydrophobic interaction is active in that case.
      The Cf-conjugation improved the penetration ability of Penetratin and Dhvar4
      suggesting that both the highly charged character (Z/n) and the increased
      hydrophobicity by Cf-conjugation present important contribution to membrane
      interaction. This effect might also responsible for the observed high in vitro
      internalisation rate of Penetratin and Dhvar4, while according to in vitro
      studies they did not cause damage of cell membrane. From the experiments with the
      given seven cationic peptides, it can be concluded that the Cf-conjugation alters
      the degree of membrane interaction of such peptides which are moderately
      hydrophobic and highly charged.

PMID- 30099596
TI  - Correction to: Ten weeks of branched-chain amino acid supplementation improves
      select performance and immunological variables in trained cyclists.
AB  - For the author R. Mac Thompson, the first name should be R. Mac and the last name
      should be Thompson. On SpringerLink the name is listed correctly, but on PubMed
      he is listed as Mac Thompson R.

PMID- 30099598
TI  - Bacterial Glycoengineering as a Biosynthetic Route to Customized Glycomolecules.
AB  - Bacteria have garnered increased interest in recent years as a platform for the
      biosynthesis of a variety of glycomolecules such as soluble oligosaccharides,
      surface-exposed carbohydrates, and glycoproteins. The ability to engineer
      commonly used laboratory species such as Escherichia coli to efficiently
      synthesize non-native sugar structures by recombinant expression of enzymes from
      various carbohydrate biosynthesis pathways has allowed for the facile generation
      of important products such as conjugate vaccines, glycosylated outer membrane
      vesicles, and a variety of other research reagents for studying and understanding
      the role of glycans in living systems. This chapter highlights some of the key
      discoveries and technologies for equipping bacteria with the requisite
      biosynthetic machinery to generate such products. As the bacterial glyco-toolbox
      continues to grow, these technologies are expected to expand the range of
      glycomolecules produced recombinantly in bacterial systems, thereby opening up
      this platform to an even larger number of applications.

PMID- 30099597
TI  - Location of Reference Electrode Does Not Interfere on Electromyographic
      Parameters in the Domains of Time and Frequency.
AB  - There is currently little information on the positioning of reference electrode
      (RE). It is generally accepted that it must be positioned on electrically neutral
      tissues, such as tendons or bony prominences. The objective of this study is to
      analyze the characteristics of the electromyographic signal (EMG) for different
      positions of RE as well as at different levels of muscle contraction. Signals
      from the brachial biceps and triceps were recorded from 18 healthy women (BMI:
      21.20 kg/m2 +/- 1.72; mean age: 21.94 +/- 1.98 years old) during 100 and 50%
      maximum flexion voluntary isometric contractions, as well as at rest. For each
      situation, the RE was randomly positioned in 4 different locations: a)
      homolateral acromion; b) homolateral brachial biceps; c) styloid process of the
      contralateral ulna; and d) lateral malleolus of the contralateral ankle. For
      statistical analysis, Shapiro-Wilk and Kruskal-Wallis tests were used, followed
      by Dunn's post-hoc test, at a significance level of 5% (p < 0.05). RMS,
      normalized RMS, PSD, median frequency and levels of energy at 60 Hz, 120 Hz and
      180 Hz were assessed for the different sites of RE. The results show that the
      positioning of the RE on the four experimental locations did not change important
      features of the electromyographic signals in the time and frequency domains, for
      the three levels of isometric contractions studied. Such findings compel us to re
      think the current trend regarding the RE position followed by the great majority
      of the researches in areas such as physical therapy.

PMID- 30099599
TI  - Rocuronium pharmacodynamic models for published five pharmacokinetic models: age
      and sex are covariates in pharmacodynamic models.
AB  - PURPOSE: Equilibration rate constant is necessary to calculate effect-site
      concentration, which is useful to control drug effect. We developed
      pharmacodynamic models for published five compartmental pharmacokinetic models
      published by Wierda, Szenohradszky, Cooper, Alvarez-Gomez, and McCoy. METHODS: We
      used 3848 train-of-four ratios from 15 male and nine female patients (21-76
      years; 44-93 kg body weight; 148-181 cm height; and 17.3-29.8 kg/m2 body mass
      index) as pharmacodynamic measures, which were collected at the start of 0.6
      mg/kg rocuronium administration until the end of the surgery. Effect compartment
      was assumed to be connected to central compartment of the pharmacokinetic model
      with equilibration rate constant (ke0). Sigmoid Emax model was fitted to describe
      the relationship between train-of-four ratio and effect-site concentration. Age,
      sex, and body mass index were assessed as possible covariates of the following
      model parameters: ke0, effect-site concentration for half of maximum effect, and
      the steepness of the effect-site concentration versus effect relationship.
      RESULTS: The duration of neuromuscular monitoring was 69 (37-129) [median
      (range)] min. All pharmacodynamic models included age and three included sex as
      significant covariates. Ke0 values ranged between 0.0820 and 0.247 depending on
      the pharmacokinetic model. The time-courses of the effect-site concentration were
      similar among the pharmacodynamic models for Wierda, Cooper, and Alvarez-Gomez
      pharmacokinetic models, which were lower than that for the Szenohradszky
      pharmacokinetic model. CONCLUSION: Each pharmacodynamic model with the
      corresponding pharmacokinetic model can be described the time course of
      rocuronium effect appropriately. The required effect-site concentration of
      rocuronium for a pharmacodynamic effect was depending on the applied models.

PMID- 30099600
TI  - Characterization of the human ridged and non-ridged skin: a comprehensive
      histological, histochemical and immunohistochemical analysis.
AB  - The structure of the human skin is directly dependent on its location and the
      mechanical forces to which it is subjected. In the present work, we have
      performed a comprehensive analysis of the human ridged and non-ridged skin to
      identify the differences and similarities between both skin types. For this
      purpose, human skin samples were obtained from dorsal hand skin (DHS), palmar
      hand skin (PHS), dorsal foot skin (DFS) and plantar foot skin (PFS) from the same
      cadaveric donors. Histological, histochemical and semiquantitative and
      quantitative immunohistochemical analyses were carried out to evaluate the
      epidermis, dermis and basement membrane. Results show that the epithelial layer
      of ridged skin had larger cell number and size than non-ridged skin for most
      strata. Melanocytes and Langerhans cells were more abundant in non-ridged skin,
      whereas Merkel cells were preferentially found in ridged skin. The expression
      pattern of CK5/6 was slightly differed between non-ridged and ridged skin.
      Involucrin expression was slightly more intense in non-ridged skin than in ridged
      skin. Collagen was more abundant in foot skin dermis than in hand skin, and in
      ridged skin as compared to non-ridged skin. Elastic fibers were more abundant in
      DHS. Biglycan was more abundant in foot skin than in hand skin. No differences
      were found for blood and lymphatic vessels. The basement membrane laminin was
      preferentially found in foot skin. These results revealed important differences
      at the epithelial, dermal and basement membrane levels that could contribute to a
      better knowledge of the human skin histology.

PMID- 30099601
TI  - Real-world use of granulocyte colony-stimulating factor in ambulatory breast
      cancer patients: a cross-sectional study.
AB  - PURPOSE: To prevent febrile neutropenia (FN), European Organisation for Research
      and Treatment of Cancer (EORTC) guidelines recommend primary prophylaxis with
      granulocyte colony-stimulating factors (PPG) for patients at high risk (>= 20%)
      of FN. In Belgium, the use of PPG is restricted by specific reimbursement
      criteria. The impact of these criteria on PPG use and adherence to guidelines is
      unknown. METHODS: This multicentre, cross-sectional, observational study aimed to
      describe PPG use by FN risk category in breast cancer patients who were scheduled
      to receive myelosuppressive chemotherapy in outpatient clinics in Belgium during
      a 2-week period between 13 October and 12 December 2014. RESULTS: In total, 490
      patients were enrolled. Median age was 57.0 years. Based on their chemotherapy
      regimen, 53.9, 5.1 and 41.0% of patients were at a low, intermediate and high
      risk of FN, respectively. Overall, 39.8% of patients received PPG (17.0, 12.0 and
      73.1% of those receiving low-, intermediate- and high-risk regimens,
      respectively). In the high-risk category, PPG was used in 89.9% of dose-dense and
      in 25.0% of classical chemotherapy regimens. PPG use was adherent to EORTC
      guidelines in 75.3% of patients (30.6% appropriate use, 44.7% appropriate non
      use). EORTC guidelines would recommend PPG use in 46.1% of this study population
      (n = 226), and its use was reimbursable in Belgium in 76.1% of these patients (n
      = 172), but only 66.4% of them received PPG (n = 150). CONCLUSIONS: Both Belgian
      reimbursement criteria and physician decision-making led to a proportion of
      patients for whom PPG treatment was recommended but finally not receiving it.

PMID- 30099602
TI  - Feasibility of using a pragmatic trials model to compare two primary febrile
      neutropenia prophylaxis regimens (ciprofloxacin versus G-CSF) in patients
      receiving docetaxel-cyclophosphamide chemotherapy for breast cancer (REaCT-TC).
AB  - PURPOSE: Optimal primary febrile neutropenia (FN) prophylaxis (i.e. ciprofloxacin
      or granulocyte-colony stimulating factors [G-CSF]) for patients receiving
      docetaxel-cyclophosphamide (TC) chemotherapy is unknown. We assessed the
      feasibility of using a novel pragmatic comparative effectiveness trial to compare
      these standard-of-care options. METHODS: Early-stage breast cancer patients
      receiving TC chemotherapy were randomised to either ciprofloxacin or G-CSF. Trial
      methodology consists of broad eligibility criteria, simply-defined endpoints,
      integrated consent model incorporating oral consent, and web-based randomisation
      in the clinic. Primary feasibility endpoints included patient and physician
      engagement (if > 50% of patients approached agree to participate and if > 50% of
      physicians approached patients for the study). Secondary clinical endpoints
      included the following: first occurrence rates of FN, treatment-related
      hospitalisation, or chemotherapy dose reduction/delay/discontinuation, as well as
      patient satisfaction with the oral consent process. RESULTS: Of 204 patients
      approached, 91.2% (186/204) agreed to randomisation. Sixteen of twenty (80%)
      participating medical oncologists randomised patients. Median patient age was
      57.7 (range 31.8-84.1). The 186 patients received 557 cycles of chemotherapy.
      Overall incidences of first events by patient (n = 186) were as follows: FN
      (18/186, 21.43%), treatment-related hospitalisation (11/186, 13.10%),
      chemotherapy reduction (19/186, 22.62%), chemotherapy discontinuation (16/186,
      19.05%), and chemotherapy delays (5/186, 5.95%). A total of 37.77% (69/186) of
      patients and 12.39% (69/557) of chemotherapy cycles had at least one of these
      first events. Patients were highly satisfied with the oral consent process.
      CONCLUSION: This study met its feasibility endpoints. This model offers a means
      of comparing standard-of-care treatments in a practical and cost-efficient
      manner. TRIAL REGISTRATION: Trial registration: ClinicalTrials.gov : NCT02173262.

PMID- 30099604
TI  - Drought negates growth stimulation due to root herbivory in pasture grasses.
AB  - Predicted increases in extreme weather are likely to alter the interactions
      between organisms within ecosystems. Whilst many studies have investigated the
      impacts of climate change on aboveground plant-insect interactions, those
      belowground remain relatively unexplored. Root herbivores can be the dominant
      taxa in grasslands, potentially altering plant community dynamics. To better
      predict the impact of climate change on grasslands, we subjected four Australian
      pasture grasses (Cynodon dactylon, Paspalum dilatatum, Microlaena stipoides and
      Lolium perenne) to contrasting rainfall regimes [a press drought (i.e. sustained,
      moderate water stress), a pulse drought (water stress followed by periodic,
      infrequent deluge event) and a well-watered control], with and without root
      herbivores; a manual root cutting treatment was also included for comparison.
      Plant growth, rooting strategy, phenology and biochemistry were measured to
      evaluate above and belowground treatment responses. Watering treatments had a
      larger effect on plant productivity than root damage treatments: press drought
      and pulse drought treatments reduced biomass by 58% and 47%, respectively. Root
      herbivore damage effects were species dependent and were not always equivalent to
      root cutting. The combination of pulse drought and root herbivory resulted in
      increased root:shoot ratios for both P. dilatatum and L. perenne, as well as
      decreased biomass and delayed flowering time for P. dilatatum. Plant biomass
      responses to root damage were greatest under well-watered conditions; however,
      root damage also delayed or prevented investment in reproduction in at least one
      species. Our findings highlight the important role of soil-dwelling invertebrates
      for forecasting growth responses of grassland communities to future rainfall
      regime changes.

PMID- 30099603
TI  - Diverse effects of the common hippopotamus on plant communities and soil
      chemistry.
AB  - The ecological importance of the common hippopotamus (Hippopotamus amphibius) in
      aquatic ecosystems is becoming increasingly well known. These unique
      megaherbivores are also likely to have a formative influence on the terrestrial
      ecosystems in which they forage. In this study, we employed a novel exclosure
      design to exclude H. amphibius from experimental plots on near-river grasslands.
      Our three-year implementation of this experiment revealed a substantial influence
      of H. amphibius removal on both plant communities and soil chemistry. H.
      amphibius significantly reduced grassland canopy height, increased the leafiness
      of common grasses, reduced woody plant abundance and size, and increased the
      concentrations of several soil elements. Many of the soil chemistry changes that
      we experimentally induced by exclusion of H. amphibius were mirrored in the soil
      chemistry differences between naturally occurring habitats of frequent (grazing
      lawns) and infrequent (shrub forest) use by H. amphibius and other grazing
      herbivores. In contrast to existing hypotheses regarding grazing species, we
      found that H. amphibius had little effect on local plant species richness.
      Simultaneous observations of exclosures designed to remove all large herbivores
      revealed that H. amphibius removal had ecologically significant impacts, but that
      the removal of all species of large herbivores generated more pronounced impacts
      than the removal of H. amphibius alone. In aggregate, our results suggest that H.
      amphibius have myriad effects on their terrestrial habitats that likely improve
      the quality of forage available for other herbivores. We suggest that ongoing
      losses of this vulnerable megaherbivore are likely to cause significant
      ecological change.

PMID- 30099605
TI  - Scale-dependent effects of conspecific flower availability on pollination
      quantity and quality in an invasive shrub.
AB  - Pollen limitation can strongly influence reproduction of pollinator-dependent
      plants. Flower abundance can affect pollination 'quantity' and 'quality' due to
      its influence on pollen availability and foraging patterns of pollinators,
      ultimately impacting on seed production. We complemented individual-based
      measurements with landscape-level metrics to assess the influence of conspecific
      flower availability at different spatial scales on the quantity and quality
      components of pollination, and their impact on seed production in the invasive
      shrub Cytisus scoparius. In 2013-2014, we sampled 40 C. scoparius populations in
      Nahuel Huapi National Park, Patagonia (Argentina). In each population, we
      estimated the proportion of tripped flowers, fruit- and seed-set in five randomly
      selected individuals. The proportion of tripped flowers and the proportion of
      them setting fruit were used as proxies of pollination quantity and quality,
      respectively. Conspecific flower availability at distinct spatial scales (5-1000
      m) was estimated as the area covered by flowering C. scoparius from color aerial
      photographs. Flower availability influenced seed output due to contrasting scale
      dependent effects on pollination quantity and quality. Increasing flower
      availability at the landscape-scale reduced pollination quantity, whereas at the
      neighborhood-scale it increased pollination quality. The overall positive effect
      of flower availability on seed output at the neighborhood scale was slightly
      higher than the overall negative effect at the landscape scale. Moreover,
      pollination quality had a higher positive effect on seed output than pollination
      quantity. Our results demonstrate that pollination quality may severely limit
      plant reproduction. Pollination quality limitation can act independently of
      pollination quantity limitation because these factors operate at different
      spatial scales.

PMID- 30099607
TI  - An EPIC Switch: Observations and Opportunities After Go-Live.

PMID- 30099606
TI  - Do grazers respond to or control food quality? Cross-scale analysis of algivorous
      fish in littoral Lake Tanganyika.
AB  - Food quality determines the growth rate of primary consumers and ecosystem
      trophic efficiencies, but it is not clear whether variation in primary consumer
      densities control, or is controlled by, variation in food quality. We quantified
      variation in the density and condition of an abundant algae-eating cichlid,
      Tropheus brichardi, with respect to the quality and productivity of algal
      biofilms within and across rocky coastal sites in Lake Tanganyika, East Africa.
      Adjacent land use and sediment deposition in the littoral zone varied widely
      among sites. Tropheus brichardi maximized both caloric and phosphorus intake at
      the local scale by aggregating in shallow habitats: algivore density decreased
      with depth, tracking attached algae productivity (rETRMAX) remarkably well (r2 =
      0.84, P = 0.00033). In contrast, algivore density was unrelated to among-site
      variation in algal productivity. Rather, there was significant increase in algal
      quality (r2 = 0.44, P = 0.011) and decrease in algal biomass (r2 = 0.53, P =
      0.0068) with T. brichardi density across sites, consistent with strong top-down
      control of primary producers. The amount of inorganic sediment on rock surfaces
      was the strongest predictor of among-site variation in algivore density (r2 =
      0.69, P = 0.00096), and algivore gut length increased with sedimentation (r2 =
      0.36, P = 0.034). These patterns indicate extrinsic and top-down forcing of algal
      food quality and quantity across coastal landscapes, combined with adaptive
      habitat selection by fish at the local scale. Factors that degrade food quality
      by decreasing algal nutrient content or diluting the resource with indigestible
      material are likely to depress grazer densities, potentially dampening top-down
      control in high-light, low-nutrient aquatic ecosystems.

PMID- 30099608
TI  - Determination of bacterial DNA based on catalytic oxidation of cysteine by G
      quadruplex DNAzyme generated from asymmetric PCR: Application to the colorimetric
      detection of Staphylococcus aureus.
AB  - A one-step, one-tube colorimetric assay is described for the detection of
      bacterial double-stranded DNA (dsDNA). It utilizes a G-quadruplex DNAzyme
      produced by an asymmetric polymerase chain reaction (As-PCR) that catalyzes the
      oxidation of cysteine to form cystine. This results in the formation of
      oligonucleotide-modified gold nanoparticles via triplex formation, and eventually
      in a color change from red to blue that occurs within about 10 mins. This can be
      measured by ratiometric colorimetric (at 525 and 600 nm). The limit of detection
      (LOD) for the model analyte (dsDNA of Staphylococcus aureus (S. aureus)) is as
      low as 0.28 pg per 0.05 mL with a good linear response ranging from 16.0 fg.MUL-1
      to 1.6 ng.MUL-1. This is much lower than previously reported LODs. The assay is
      highly selective for S. aureus dsDNA over a range of other bacterial DNAs.
      Conceivably, it provides an attractive alternative tool for rapid detection of
      bacterial dsDNA as required in pathogen screening in the food industry. Graphical
      abstract Schematic presentation of a colorimetric assay for bacterial DNA. It is
      based on the catalytic activity of a G-quadruplex DNAzyme that is formed by an
      asymmetric PCR involving triplex DNA formation and gold nanoparticle (AuNPs)
      aggregation.

PMID- 30099609
TI  - Peak oxygen uptake, ventilatory threshold, and arterial stiffness in adolescents.
AB  - PURPOSE: To investigate the associations of peak oxygen uptake ([Formula: see
      text]) and [Formula: see text] at ventilatory threshold ([Formula: see text] at
      VT) with arterial stiffness in adolescents. METHODS: The participants were 55
      adolescents (36 girls, 19 boys) aged 16-19 years. Aortic pulse wave velocity
      (PWVao) and augmentation index (AIx%) were measured by non-invasive oscillometric
      device from right brachial artery level. [Formula: see text] was directly
      measured during a maximal ramp test on a cycle ergometer. [Formula: see text] at
      VT was determined using the equivalents for ventilation ([Formula: see
      text]/[Formula: see text] and [Formula: see text]/[Formula: see text]). [Formula:
      see text] and [Formula: see text] at VT were normalised for body mass (BM) and
      lean mass (LM). Data were analysed using linear regression analyses and analysis
      of covariance adjusted for age and sex. RESULTS: [Formula: see text] normalised
      for BM (beta = - 0.445, 95% CI - 0.783 to - 0.107) and [Formula: see text]
      normalised for LM (beta = - 0.386, 95% CI - 0.667 to - 0.106) were inversely
      associated with PWVao. A higher [Formula: see text] at VT normalised for BM (beta
      = - 0.366, 95% CI - 0.646 to - 0.087) and LM (beta = - 0.321, 95% CI - 0.578 to -
      0.064) was associated with lower PWVao. Adolescents in the lowest third of
      [Formula: see text] by LM (6.6 vs. 6.1 m/s, Cohen's d = 0.33) and [Formula: see
      text] at VT by LM (6.6 vs. 6.0 m/s, Cohen's d = 0.33) had a higher PWVao than
      those in the highest third of [Formula: see text] or [Formula: see text] at VT by
      LM. CONCLUSIONS: Higher [Formula: see text] and [Formula: see text] at VT by BM
      and LM were related to lower arterial stiffness in adolescents. Normalising
      [Formula: see text] and [Formula: see text] at VT for LM would provide the most
      appropriate measure of cardiorespiratory fitness in relation to arterial
      stiffness.

PMID- 30099610
TI  - Physiological and transcriptomic responses of reproductive stage soybean to
      drought stress.
AB  - KEY MESSAGE: The dynamic alterations of the physiological and molecular processes
      in reproductive stage soybean indicated the dramatic impact caused by drought.
      Drought is a major abiotic stress that limits soybean (Glycine max) production.
      Most prior studies were focused on either model species or crops that are at
      their vegetative stages. It is known that the reproductive stage of soybean is
      more susceptible to drought. Therefore, an understanding on the responsive
      mechanisms during this stage will not only be important for basic plant
      physiology, but the knowledge can also be used for crop improvement via either
      genetic engineering or molecular breeding. In this study, physiological
      measurements and RNA-Seq analysis were used to dissect the metabolic alterations
      and molecular responses in the leaves of soybean grown at drought condition.
      Photosynthesis rate, stomata conductance, transpiration, and water potential were
      reduced. The activities of SOD and CAT were increased, while the activity of POD
      stayed unchanged. A total of 2771 annotated genes with at least twofold changes
      were found to be differentially expressed in the drought-stressed plants in which
      1798 genes were upregulated and 973 were downregulated. Via KEGG analysis, these
      genes were assigned to multiple molecular pathways, including ABA biogenesis,
      compatible compound accumulation, secondary metabolite synthesis, fatty acid
      desaturation, plant transcription factors, etc. The large number of
      differentially expressed genes and the diverse pathways indicated that soybean
      employs complicated mechanisms to cope with drought. Some of the identified genes
      and pathways can be used as targets for genetic engineering or molecular breeding
      to improve drought resistance in soybean.

PMID- 30099611
TI  - The wheat TdRL1 is the functional homolog of the rice RSS1 and promotes plant
      salt stress tolerance.
AB  - KEY MESSAGE: Rice rss1 complementation assays show that wheat TdRL1 and RSS1 are
      true functional homologs. TdRL1 over-expression in Arabidopsis conferred salt
      stress tolerance and alleviated ROS accumulation. Plants have developed highly
      flexible adaptive responses to their ever-changing environment, which are often
      mediated by intrinsically disordered proteins (IDP). RICE SALT SENSITIVE 1 and
      Triticum durum RSS1-Like 1 protein (TdRL1) are both IDPs involved in abiotic
      stress responses, and possess conserved D and DEN-Boxes known to be required for
      post-translational degradation by the APC/Ccdc20 cyclosome. To further understand
      their function, we performed a computational analysis to compare RSS1 and TdRL1
      co-expression networks revealing common gene ontologies, among which those
      related to cell cycle progression and regulation of microtubule (MT) networks
      were over-represented. When over-expressed in Arabidopsis, TdRL1::GFP was present
      in dividing cells and more visible in cortical and endodermal cells of the Root
      Apical Meristem (RAM). Incubation with the proteasome inhibitor MG132 stabilized
      TdRL1::GFP expression in RAM cells showing a post-translational regulation.
      Moreover, immuno-cytochemical analyses of transgenic roots showed that TdRL1 was
      present in the cytoplasm and within the microtubular spindle of mitotic cells,
      while, in interphasic cells, it was rather restricted to the cytoplasm with a
      spotty pattern at the nuclear periphery. Interestingly in cells subjected to
      stress, TdRL1 was partly relocated into the nucleus. Moreover, TdRL1 transgenic
      lines showed increased germination rates under salt stress conditions as compared
      to wild type. This enhanced salt stress tolerance was associated to an
      alleviation of oxidative damage. Finally, when expressed in the rice rss1 mutant,
      TdRL1 suppressed its dwarf phenotype upon salt stress, confirming that both
      proteins are true functional homologs required for salt stress tolerance in
      cereals.

PMID- 30099613
TI  - Regulation of Mitochondrial and Cytosol Antioxidant Systems of Fenugreek
      (Trigonella foenum graecum L.) Exposed to Nanosized Titanium Dioxide.
AB  - In the present study, the interactions between nanoparticle (NP) exposure, root
      application and plants were examined. NPs are potentially responsible for
      conformational changes in polysaccharides, lipids, proteins, pectin, suberin and
      lignin molecules. 4 days of treatment with metal oxide caused a statistically
      significant increase in nicotinamide adenine dinucleotide oxidase activity in
      mitochondria and cytosol. Following exposure to TiO2NP, even lipid peroxidation
      levels decreased in the mitochondria (leaves, stem and root) and in the cytosol
      (leaves and root), although it increased in the cytosol of the stem.
      Malondialdehyde accumulation was found to be higher in the cytosol compared to
      the mitochondria of stems, and in the cytosol of leaves and roots. NPs caused
      alterations in metabolism, antioxidant enzyme activities (guaiacol peroxidase,
      catalase and ascorbate peroxidase) and the generation of oxidative stress.
      Effects caused by exposures to NPs were influenced by differences in metabolic
      responses in plant parts, plant compartments, the period of exposure and the NP
      doses.

PMID- 30099614
TI  - Pollution and Risk of PAHs in Surface Sediments from the Tributaries and Their
      Relation to Anthropogenic Activities, in the Main Urban Districts of Chongqing
      City, Southwest China.
AB  - Concentrations, sources and risk of 16 priority polycyclic aromatic hydrocarbons
      (PAHs) were investigated in surface sediments from 19 representative tributaries
      in a regional scale of Chongqing City. The total concentration of 16 PAHs
      (SigmaPAHs) ranged from 221 to 3205 ng g-1 with a mean of 1055 ng g-1. Most
      tributaries of the Jialing River exhibited significantly higher SigmaPAHs
      concentrations (mean 1864 ng g-1) compared to those flowing into the Yangtze
      River (mean 787 ng g-1). Isomeric ratio and hierarchical clustering analysis
      showed combustion may impact sedimentary PAHs at most center sites of the City,
      while PAHs at most sites were mixed of petrogenic and pyrogenic sources. Toxicity
      equivalency concentration for carcinogenic PAH were 2-4 times more than the Dutch
      limit. More comprehensive assessment of safety is suggested to reduce
      environmental risk of PAHs in sediments.

PMID- 30099612
TI  - Overexpressing heat-shock protein OsHSP50.2 improves drought tolerance in rice.
AB  - KEY MESSAGE: OsHSP50.2, an HSP90 family gene up-regulated by heat and osmotic
      stress treatments, positively regulates drought stress tolerance probably by
      modulating ROS homeostasis and osmotic adjustment in rice. Heat-shock proteins
      (HSPs) serve as molecular chaperones for a variety of client proteins in abiotic
      stress response and play pivotal roles in protecting plants against stress, but
      the molecular mechanism remains largely unknown. Here, we report an HSP90 family
      gene, OsHSP50.2, which acts as a positive regulator in drought stress tolerance
      in rice (Oryza sativa). OsHSP50.2 was ubiquitously expressed and its transcript
      level was up-regulated by heat and osmotic stress treatments. Overexpression of
      OsHSP50.2 in rice reduced water loss and enhanced the transgenic plant tolerance
      to drought and osmotic stresses. The OsHSP50.2-overexpressing plants exhibited
      significantly lower levels of electrolyte leakage and malondialdehyde (MDA) and
      less decrease of chlorophyll than wild-type plants under drought stress.
      Moreover, the OsHSP50.2-overexpressing plants had significantly higher SOD
      activity under drought stress compared with the wild type. These results imply
      that OsHSP50.2 positively regulates drought stress tolerance in rice, probably
      through the modulation of reactive oxygen species (ROS) homeostasis.
      Additionally, the OsHSP50.2-overexpressing plants accumulated significantly
      higher content of proline than the wild type under drought stress, which
      contributes to the improved protection ability from drought stress damage via
      osmotic adjustment. Our findings reveal that OsHSP50.2 plays a crucial role in
      drought stress response, and it may possess high potential usefulness in drought
      tolerance improvement of rice.

PMID- 30099615
TI  - Endoplasmic reticulum stress and monogenic kidney diseases in precision
      nephrology.
AB  - The advent of next-generation sequencing (NGS) in recent years has led to a rapid
      discovery of novel or rare genetic variants in human kidney cell genes, which is
      transforming the risk assessment, diagnosis, and treatment of kidney disease.
      Mutations may lead to protein misfolding, disruption of protein trafficking, and
      endoplasmic reticulum (ER) retention. An imbalance between the load of misfolded
      proteins and the folding capacity of the ER causes ER stress and unfolded protein
      response. Mutations in nephrin (NPHS1), podocin (NPHS2), laminin beta2 (LAMB2),
      and alpha-actinin-4 (ACTN4) have been shown to induce ER stress in HEK293 cells
      and podocytes in hereditary nephrotic syndromes; various founder mutations in
      collagen IV alpha chains (COL4A) have been demonstrated to activate podocyte ER
      stress in collagen IV nephropathies; and mutations in uromodulin (UMOD) have been
      reported to trigger tubular ER stress in autosomal dominant tubulointerstitial
      kidney disease. Meanwhile, ER resident protein SEC63 may modify disease severity
      in autosomal dominant polycystic kidney disease. These findings underscore the
      importance of ER stress in the pathogenesis of monogenic kidney disease.
      Recently, we have identified mesencephalic astrocyte-derived neurotrophic factor
      (MANF) and cysteine-rich with EGF-like domains 2 (CRELD2) as urinary ER stress
      biomarkers in ER stress-mediated kidney diseases.

PMID- 30099616
TI  - More assortative mating in US compared to European parents and spouses of
      patients with bipolar disorder: implications for psychiatric illness in the
      offspring.
AB  - The effect of assortative mating on offspring is often not considered. Here, we
      present data on illness in the spouse and the parents of patients with bipolar
      disorder as they affect illness in the offspring. A history of psychiatric
      illness (depression, bipolar disorder, suicide attempt, alcohol abuse, drug
      abuse, and "other" illness) was elicited for the parents, spouse, and the
      offspring of 968 patients with bipolar disorder (540 of whom had children) who
      gave informed consent for participation in a treatment outcome network.
      Assortative mating for a mood disorder in the spouse and parents in those from
      the United States (US) was compared to those from the Netherlands and Germany and
      related to illnesses in the offspring. There was more illness and assortative
      mating for a mood disorder in both the spouse and patient's parents from the US
      compared to Europe. In the parents of the US patients, assortative mating for a
      mood disorder was associated with more depression, bipolar disorder, alcohol, and
      "other" illness in the offspring. Compared to the Europeans, there was more
      assortative mating for mood and other disorders in two generations of those from
      the US. This bilineal positivity for a parental mood disorder was related to more
      depression a second generation later in the patients' offspring. In clinical
      assessment of risk of illness in the offspring, the history of psychiatric
      illness in the spouse and patient's parents might provide additional information.

PMID- 30099618
TI  - Rigid dilatation of pediatric laryngotracheal stenosis as an adequate alternative
      to balloon dilatation.
AB  - INTRODUCTION: Endoscopic balloon dilation (EBD) is the mainstay of endoscopic
      therapy for laryngotracheal stenosis (LTS), although there is no evidence that it
      achieves better results than traditional rigid laryngeal dilators. Rigid bougie
      dilators are less expensive and easier to use, and confer the advantage of
      providing tactile information about the stenosis to the surgeon. We analyzed the
      outcome of endoscopic rigid bougie dilatation of LTS in a large series of
      children and compared it to the reported results of EBD in the same setting.
      PATIENTS AND METHODS: All cases of pediatric LTS treated by endoscopic rigid
      dilatation in a tertiary referral center between 2006 and 2015 were
      retrospectively studied. They were divided into a primary dilatation group (PDG)
      and a post-reconstruction dilatation group (PRG). The PDG children had no history
      of reconstructive airway surgery, and dilatation was the major treatment
      approach. The PRG children underwent dilatations after airway reconstruction
      surgery as part of routine postoperative management. A successful primary outcome
      was defined as improvement of dyspnea and achievement of a functional airway
      without reconstructive laryngotracheal surgery or need for a tracheostomy at
      final follow-up. RESULTS: Sixty-two children (68 cases, mean age 5.1 years, range
      0.7-17.2) underwent 156 endoscopic rigid dilatations. Successful outcome was
      achieved in 48 cases (70.6%), 73.0% in the PDG and 67.7% in the PRG. There were
      no procedure-related adverse events. CONCLUSIONS: Endoscopic rigid dilatation is
      a relatively inexpensive and efficacious tool in endoscopic management of
      pediatric LTS. Its success rates are in the same range as those of EBD.

PMID- 30099621
TI  - LI-RADS version 2018: What is new and what does this mean to my radiology
      reports?

PMID- 30099620
TI  - To be or not to be Wilbrand's knee? A question that is looking for an answer.

PMID- 30099619
TI  - Neuroendoscopy for post-infective hydrocephalus in children.
AB  - The treatment of hydrocephalus has changed in recent years with better imaging
      and introduction of endoscopic procedures as well as enhanced shunts. Indications
      of endoscopic third ventriculostomy (ETV) are now more refined with better
      quantification of outcome. This article reviews the current state of
      neuroendoscopy for infective hydrocephalus in children. The roles of third
      ventriculostomy as a primary procedure or after shunt malfunction, endoscopic
      interventions in multiloculated hydrocephalus and introduction of
      intraventricular lavage to salvage severely infected children are evaluated.

PMID- 30099617
TI  - Sleep in Parkinson's Disease with Impulse Control Disorder.
AB  - PURPOSE OF REVIEW: This paper aims to explore the relationship between impulse
      control disorders (ICDs) and sleep problems in patients with Parkinson's disease
      (PD) among scientific literature. RECENT FINDINGS: Previously published results
      are controversial and sometimes inconclusive. ICDs and sleep disruption represent
      important non-motor features of Parkinson's disease, responsible for reducing
      quality of life and increasing burden of disease. The relationship between sleep
      problems and ICDs is complex and bidirectional. Indeed, sleep disturbances and
      fragmentation may play a crucial role in increasing susceptibility to impulsive
      behavior and may represent a risk factor for developing ICDs in PD patients.
      Moreover, REM sleep behavior disorder (RBD) and restless legs syndrome (RLS) have
      been indicated as independent risk factors for ICDs in PD patients. On the other
      hand, also ICDs may lead to sleep restriction and fragmentation, suggesting a
      bidirectional relationship. The association between sleep problems and ICDs in PD
      is far from being completely understood. Further studies are needed to confirm
      the nature of this relationship and its pathophysiology.

PMID- 30099622
TI  - Successive complementary model-based experimental designs for parameter
      estimation of fed-batch bioreactors.
AB  - When a dynamic model is used for the description of (fed-)batch bioreactors, it
      is typical that the model parameters are highly correlated to each other. In this
      case, it is important to keep the parameter correlation as small as possible to
      obtain a reliable set of parameter estimates. In this study, we propose an
      anticorrelation parameter estimation scheme that can be best utilized when a
      number of different batch experiments are sequentially processed. The scheme
      iteratively performs parameter estimation and model-based design of experiment
      (MBDOE) at the beginning and between the batches. The important difference from
      the existing approaches is that the MBDOE objective is defined according to the
      system analysis performed a priori, so that each new batch supplements what is
      lacking from the previous batches combined, in terms of information. The use of
      the scheme is illustrated on a fed-batch bioreactor model.

PMID- 30099623
TI  - Reclamation of wastewater organics via two-stage growth of bacteria-then
      oleaginous phagotrophic algae.
AB  - A substantial amount of organic matter is wasted in current wastewater treatment
      processes. To reclaim the value of organic matter, a two-stage continuous-flow
      open process has been developed by utilizing the capability of phagotrophic algae
      in ingesting bacterial cells. In this process, wastewater is first pumped into a
      bacteria tank to grow bacterial cells, and then the effluent containing grown
      bacteria cells is fed to an algae tank to grow phagotrophic algae. The operation
      conditions such as dilution rate, pH, and dissolved oxygen level were
      comprehensively investigated and optimized with long-term tests. Results show
      that phagotrophic algae can be stably cultivated with wastewater organics through
      this open process without costly chemical/physical sterilization. The produced
      phagotrophic algae had high lipid content and can be potentially used as biofuel
      feedstock.

PMID- 30099624
TI  - Translational Aspects of Brown Fat Activation by Food-Derived Stimulants.
AB  - Since the rediscovery of brown adipose tissue (BAT) in humans, its energy
      dissipating ability has been well-recognized. The negative correlations of BAT
      activity with adiposity and insulin sensitivity provided an obvious rationale for
      discerning reliable and practical strategies for stimulating BAT. Though cold
      exposure or use of pharmacological adrenomimetics can activate BAT, they may have
      adverse effects. Therefore, determining alternative stimulants of BAT with lower
      risks such as commonly used food ingredients is highly desirable. Recent
      observations revealed that chemical activation of temperature-sensitive transient
      receptor potential (TRP) channels by food ingredients can recruit BAT in humans.
      Furthermore, animal studies have identified several food-derived stimulants of
      BAT acting through multiple mechanisms distinct from a TRP-mediated process.
      Dietary compounds acting as an activator of Sirtuin 1, a critical regulator of
      mitochondrial biogenesis and brown adipocyte differentiation, are one such class
      of promising food-derived BAT activators in humans. While the individual effects
      of various dietary factors are increasingly established in a laboratory setting,
      the potential synergistic effects of multiple stimulants on BAT remain to be
      tested in a clinical environment. These investigations may support the
      development of efficient, flexible dietary regimens capable of boosting BAT
      thermogenesis.

PMID- 30099625
TI  - Techniques and Applications of Magnetic Resonance Imaging for Studying Brown
      Adipose Tissue Morphometry and Function.
AB  - The present review reports on the current knowledge and recent findings in
      magnetic resonance imaging (MRI) and spectroscopy (MRS) of brown adipose tissue
      (BAT). The work summarizes the features and mechanisms that allow MRI to
      differentiate BAT from white adipose tissue (WAT) by making use of their distinct
      morphological appearance and the functional characteristics of BAT. MR is a
      versatile imaging modality with multiple contrast mechanisms as potential
      candidates in the study of BAT, targeting properties of 1H, 13C, or 129Xe nuclei.
      Techniques for assessing BAT morphometry based on fat fraction and markers of BAT
      microstructure, including intermolecular quantum coherence and diffusion imaging,
      are first described. Techniques for assessing BAT function based on the
      measurement of BAT metabolic activity, perfusion, oxygenation, and temperature
      are then presented. The application of the above methods in studies of BAT in
      animals and humans is described, and future directions in MR study of BAT are
      finally discussed.

PMID- 30099626
TI  - Management of patients with rectal prolapse: the 2017 Dutch guidelines.
AB  - BACKGROUND: Rectal prolapse-both external rectal prolapse and internal rectal
      prolapse-is a disabling condition. In view of the overwhelming number of surgical
      procedures described for the treatment of rectal prolapse, a comprehensive update
      concerning the diagnostic and therapeutic pathway for this condition is required
      to draw recommendations for clinical practice. This initiative was commissioned
      by the Dutch Association for Surgery (Nederlandse Vereniging voor Heelkunde) as a
      multidisciplinary collaboration. METHODS: Nine questions outlining the diagnostic
      approach, conservative and surgical management of rectal prolapse were selected.
      A systematic literature search for evidence was then conducted in the Medline and
      Embase databases. RESULTS: Recommendations included diagnostic approach, methods
      to assess complaints of fecal incontinence and/or obstructive defecation and
      treatment options, both conservative and surgical. A level of evidence was
      assigned to each statement following the Grades of Recommendation Assessment,
      Development and Evaluation (GRADE) system. CONCLUSIONS: These guidelines for
      clinical practice are useful in the diagnosis and treatment of rectal prolapse.
      There are many statements requiring a higher level of evidence due to a lack of
      studies.

PMID- 30099628
TI  - Racial variation in receipt of quality radiation therapy for prostate cancer.
AB  - PURPOSE: Racial disparities are apparent in the management and outcomes for
      prostate cancer; however, disparities in compliance to quality measures for
      radiation therapy for prostate cancer have not been previously studied.
      Therefore, the goal of the study was to characterize disparities in the
      compliance rates with quality measures. METHODS: The comparative effectiveness
      analysis of radiation therapy and surgery study is a population-based,
      prospective cohort study that enrolled 3708 men with clinically localized
      prostate cancer from 2011 to 2012. Compliance with 5 radiation-specific quality
      measures endorsed by national consortia as of 2011 was assessed, and compliance
      was compared by race using logistic regression. RESULTS: Overall, 604 men
      received definitive external beam radiation therapy (EBRT) of which 20% were self
      reported black, 74% non-Hispanic white, and 6% Hispanic. Less than two-thirds of
      black and Hispanic men received EBRT that was compliant with all available
      quality measures (p = 0.012). Compared to white men, black men were less likely
      to receive dose-escalated EBRT (95% vs. 87%, p = 0.011) and less likely to avoid
      unnecessary pelvic radiation for low-risk disease (99% vs. 20%, p < 0.001).
      Compared to white men, Hispanic men were less likely to undergo image guidance
      (87% vs. 71%, p = 0.04). Black and Hispanic men were more likely to receive EBRT
      from low-quality providers than white men. CONCLUSIONS: Addressing disparities in
      access to providers that meet quality guidelines, and improving adherence to
      evidence-based processes of care may decrease racial/ethnic disparities in
      prostate cancer outcomes.

PMID- 30099627
TI  - Electrophysiological Signatures of Intrinsic Functional Connectivity Related to
      rTMS Treatment for Mal de Debarquement Syndrome.
AB  - To determine intrinsic functional connectivity (IFC) related to symptom changes
      induced by rTMS in mal de debarquement syndrome (MdDS), a motion perceptual
      disorder induced by entrainment to oscillating motion. Twenty right-handed women
      (mean age: 52.9 +/- 12.6 years; mean duration illness: 35.2 +/- 24.2 months) with
      MdDS received five sessions of rTMS (1 Hz right DLPFC, 10 Hz left DLPFC) over
      consecutive days. High-density (128-channel) resting-state EEG were recorded
      prior to and following treatment sessions and analyzed using a group-level
      independent component (IC) analysis. IFC between 19 ICs was quantified by inter
      IC phase coherence (ICPC) in six frequency bands (delta, theta, low alpha, high
      alpha, beta, gamma). Correlational analyses between IFCs and symptoms were
      performed. Symptom improvement after rTMS was significantly correlated with (1)
      an increase in low alpha band (8-10 Hz) IFC but a decrease of IFC in all other
      bands, and (2) high baseline IFC in the high alpha (11-13 Hz) and beta bands (14
      30 Hz). Most treatment related IFC changes occurred between frontal and parietal
      regions with a linear association between the degree of symptom improvement and
      the number of coherent IFC changes. Frequency band and region specific IFC
      changes correlate with and can predict symptom changes induced by rTMS over DLPFC
      in MdDS. MdDS symptom response correlates with high baseline IFC in most
      frequency bands. Treatment induced increase in long-range low alpha IFC and
      decreases in IFC in other bands as well as the proportion of coherent IFC changes
      correlate with symptom reduction.

PMID- 30099629
TI  - Temporal reliability of serum soluble and endogenous secretory receptors for
      advanced glycation end-products (sRAGE and esRAGE) in healthy women.
AB  - PURPOSE: The soluble receptor for advanced glycation end-products (sRAGE) and
      endogenous secretory RAGE (esRAGE) have been considered as biomarkers of several
      chronic diseases. However, the temporal reliability of their concentrations in
      the circulation is yet to be demonstrated. We evaluated whether a single
      measurement of serum sRAGE and esRAGE could serve as an estimate for usual serum
      levels in epidemiologic studies. METHODS: Serum sRAGE and esRAGE were measured
      using ELISAs in three yearly samples from 36 participants in the New York
      University Women's Health Study. The intraclass correlation coefficient (ICC) was
      used to evaluate temporal reliability. RESULTS: The intra- and inter-batch
      coefficients of variation were 3.0% and 14.8% for sRAGE and 6.5% and 34.7% for
      esRAGE, and decreased to 0.4% and 2.1% for sRAGE and 1.0% and 6.3% for esRAGE
      after log2-transformation of the data. On the original scale, the ICCs of a
      single measurement of serum sRAGE and esRAGE were 0.89 (95% CI 0.82-0.94) and
      0.87 (95% CI 0.79-0.93), respectively, and were similar using log2-transformed
      data. CONCLUSION: Our results indicate that a single measurement of serum sRAGE
      and esRAGE is a sufficiently reliable measure of their usual levels that can be
      used in epidemiologic studies.

PMID- 30099630
TI  - Indoor tanning and the risk of developing non-cutaneous cancers: a systematic
      review and meta-analysis.
AB  - PURPOSE: Despite a strong association between indoor tanning and the risk of
      cutaneous cancers, the relationship between indoor tanning and non-cutaneous
      cancers is unknown. Our objective was to estimate the association of indoor
      tanning with developing non-cutaneous cancers. METHODS: We conducted a systematic
      literature review and meta-analysis of the association between indoor tanning and
      non-cutaneous cancer sites. Associations were estimated using random effects
      models. Heterogeneity was investigated through subgroup analyses and the Q-test
      and I2 statistics. RESULTS: From 15 identified studies, 33 effect estimates for
      12 cancer sites were included in the review. Adjustment for sun exposure was a
      significant source of heterogeneity in the association of indoor tanning and non
      cutaneous cancer risk (meta-regression p = 0.0043). When restricting to studies
      that adjusted for solar ultraviolet radiation (7 studies and 19 effect estimates)
      a potential increased risk was observed among ever users of indoor tanning
      devices with the risk of hematologic malignancies (pooled relative risk = 1.11;
      95% CI 0.96-1.28), with differing effects observed by hematologic types and
      subtypes of non-Hodgkin lymphoma. No association was observed among solid non
      cutaneous cancers (pooled relative risk = 0.98; 95% CI 0.94-1.19). Neither study
      design nor geographical region was significant sources of heterogeneity in these
      associations. CONCLUSION: When controlling for sun exposure, indoor tanning does
      not protect against solid non-cutaneous cancers and may increase the risk of some
      hematologic malignancies. Given the well-established relationship with skin
      cancer and potential relationship with hematologic malignancies, efforts to
      reduce the use of indoor tanning devices should continue.

PMID- 30099631
TI  - Unraveling obscurins in heart disease.
AB  - Obscurins, expressed from the single OBSCN gene, are a family of giant, modular,
      cytoskeletal proteins that play key structural and regulatory roles in striated
      muscles. They were first implicated in the development of heart disease in 2007
      when two missense mutations were found in a patient diagnosed with hypertrophic
      cardiomyopathy (HCM). Since then, the discovery of over a dozen missense,
      frameshift, and splicing mutations that are linked to various forms of
      cardiomyopathy, including HCM, dilated cardiomyopathy (DCM), and left ventricular
      non-compaction (LVNC), has highlighted OBSCN as a potential disease-causing gene.
      At this time, the functional consequences of the identified mutations remain
      largely elusive, and much work has yet to be done to characterize the disease
      mechanisms of pathological OBSCN variants. Herein, we describe the OBSCN
      mutations known to date, discuss their potential impact on disease development,
      and provide future directions in order to better understand the involvement of
      obscurins in heart disease.

PMID- 30099633
TI  - Neoadjuvant therapy for breast cancer treatment: an expert panel recommendation
      from the Brazilian Society of Breast Surgeons 2018.
AB  - PURPOSE: Breast cancer neoadjuvant chemotherapy (NAC) consists of the
      administration of cytotoxic and targeted drugs prior to breast surgery, with the
      objective of reducing the tumor burden to allow breast conservation. NAC also
      aims to improve long-term treatment outcomes such as disease-free and overall
      survival. To optimize clinical practice with the best available evidence for
      breast cancer patients in the setting of neoadjuvant treatment, the Brazilian
      Society of Breast Surgeons (Sociedade Brasileira de Mastologia-SBM) held a
      consensus conference to develop this guideline. METHODS: Twenty-two questions
      addressing relevant breast cancer neoadjuvant treatment were previously
      formulated. The voting panel comprised 25 specialists from the SBM. A consensus
      was established if there was 75% agreement. If there was less concordance, after
      discussion, the consensus was determined by a 51% concordance. RESULTS: The
      recommendations were based on the best level of scientific evidence and the
      opinion from breast cancer experts, when no such research data were available.
      CONCLUSION: This manuscript provides updated guidance according to the views of
      the SBM's experts for the clinical practice of breast cancer surgeons. This
      manuscript depicts the summarized recommendations for NAC treatment.

PMID- 30099632
TI  - Loss-of-function of Nav1.8/D1639N linked to human pain can be rescued by
      lidocaine.
AB  - Mutations in voltage-gated sodium channels are associated with altered pain
      perception in humans. Most of these mutations studied to date present with a
      direct and intuitive link between the altered electrophysiological function of
      the channel and the phenotype of the patient. In this study, we characterize a
      variant of Nav1.8, D1639N, which has been previously identified in a patient
      suffering from the chronic pain syndrome "small fiber neuropathy". Using a
      heterologous expression system and patch-clamp analysis, we show that
      Nav1.8/D1639N reduces current density without altering biophysical gating
      properties of Nav1.8. Therefore, the D1639N variant causes a loss-of-function of
      the Nav1.8 sodium channel in a patient suffering from chronic pain. Using
      immunocytochemistry and biochemical approaches, we show that Nav1.8/D1639N
      impairs trafficking of the channel to the cell membrane. Neither co-expression of
      beta1 or beta3 subunit, nor overnight incubation at 27  degrees C rescued current
      density of the D1639N variant. On the other hand, overnight incubation with
      lidocaine fully restored current density of Nav1.8/D1639N most likely by
      overcoming the trafficking defect, whereas phenytoin failed to do so. Since
      lidocaine rescues the loss-of-function of Nav1.8/D1639N, it may offer a future
      therapeutic option for the patient carrying this variant. These results
      demonstrate that the D1639N variant, identified in a patient suffering from
      chronic pain, causes loss-of-function of the channel due to impaired cell surface
      trafficking and that this trafficking defect can be rescued by lidocaine.

PMID- 30099634
TI  - Associations of preoperative breast magnetic resonance imaging with subsequent
      mastectomy and breast cancer mortality.
AB  - PURPOSE: To examine associations between pre-operative magnetic resonance imaging
      (MRI) use and clinical outcomes among women undergoing breast-conserving surgery
      (BCS) with or without radiotherapy for early-stage breast cancer. METHODS: We
      identified women from the Surveillance, Epidemiology, and End Results-Medicare
      dataset aged 67-94 diagnosed during 2004-2010 with stage I/II breast cancer who
      received BCS. We compared subsequent mastectomy and breast cancer mortality with
      versus without pre-operative MRI, using Cox regression and competing risks
      models. We further stratified by receipt of radiotherapy for subgroup analyses.
      RESULTS: Our sample consisted of 24,379 beneficiaries, 4691 (19.2%) of whom
      received pre-operative MRI. Adjusted rates of subsequent mastectomy and breast
      cancer mortality were not significantly different with and without MRI: 3.2
      versus 4.1 per 1000 person-years [adjusted hazard ratio (AHR) 0.92; 95%
      confidence interval (CI) 0.70-1.19] and 5.3 versus 8.7 per 1000 person-years (AHR
      0.89; 95% CI 0.73-1.08), respectively. In subgroup analyses, women receiving BCS
      plus radiotherapy had similar rates of subsequent mastectomy (AHR 1.17; 95% CI
      0.84-1.61) and breast cancer mortality (AHR 1.00; 95% CI 0.80-1.24) with versus
      without MRI. However, among women receiving BCS alone, MRI use was associated
      with lower risks of subsequent mastectomy (AHR 0.60; 95% CI 0.37-0.98) and breast
      cancer mortality (AHR 0.57; 95% CI 0.36-0.92). CONCLUSIONS: Pre-operative MRI was
      associated with improved outcomes among older women with breast cancer receiving
      BCS alone, but not among those receiving BCS plus radiotherapy. Further research
      is needed to identify appropriate settings for which MRI may be helpful.

PMID- 30099635
TI  - Predicting efficacy of epirubicin by a multigene assay in advanced breast cancer
      within a Danish Breast Cancer Cooperative Group (DBCG) cohort: a retrospective
      prospective blinded study.
AB  - PURPOSE: Anthracyclines remain a cornerstone in the treatment of primary and
      advanced breast cancer (BC). This study has evaluated the predictive value of a
      multigene mRNA-based drug response predictor (DRP) in the treatment of advanced
      BC with epirubicin. The DRP is a mathematical method combining in vitro
      sensitivity and gene expression with clinical genetic information from > 3000
      clinical tumor samples. METHODS: From a DBCG cohort, 140 consecutive patients
      were treated with epirubicin between May 1997 and November 2016. After patient
      informed consent, mRNA was isolated from archival formalin-fixed paraffin
      embedded primary breast tumor tissue and analyzed using Affymetrix arrays. Using
      time to progression (TTP) as primary endpoint, the efficacy of epirubicin was
      analyzed according to DRP combined with clinicopathological data collected
      retrospectively from patients' medical records. Statistical analysis was done
      using Cox proportional hazards model stratified by treatment line. RESULTS:
      Median TTP was 9.3 months. The DRP was significantly associated to TTP (P =
      0.03). The hazard ratio for DRP scores differing by 50 percentage points was 0.55
      (95% CI -0.93, one-sided). A 75% DRP was associated with a median TTP of 13
      months compared to 7 months following a 25% DRP. Multivariate analysis showed
      that DRP was independent of age and number of metastases. CONCLUSION: The current
      study prospectively validates the predictive capability of DRP regarding
      epirubicin previously shown retrospectively allowing the patients predicted to be
      poor responders to choose more effective alternatives. Randomized prospective
      studies are needed to demonstrate if such an approach will lead to increased
      overall survival.

PMID- 30099636
TI  - Potential for local resection with sentinel node basin dissection for early
      gastric cancer based on the distribution of primary sites.
AB  - BACKGROUND: Based on the sentinel node (SN) concept, function-preserving surgery
      with SN basin dissection (SNBD) can be performed for SN-negative early gastric
      cancers. Particularly, a resection area can be minimized when the SN basin and
      primary site are closely localized. The aim of this study was to compare
      probabilities of being candidates for local resection with SNBD based on tumor
      location among patients with early gastric cancer. METHODS: We retrospectively
      analyzed 358 patients who underwent surgery with SN mapping for gastric cancer in
      our institution from November 1999 to April 2014. The proportion of patients who
      had a localized single basin and the distributions of the SN basins and primary
      sites were investigated. Patients with single basin drainage excluding remote
      sentinel node basin were considered as candidates for local resection with SNBD.
      RESULTS: Of the 358 patients, 191 (53%) patients were considered eligible for
      local resection with SNBD. Patients with tumors located in the upper third of the
      stomach were more likely candidates for local resection than those with tumors in
      other locations (upper third, 68%; middle third, 50%; and lower third, 51%),
      whereas patients with tumors located in the anterior wall were less likely
      candidates than those with tumors other locations (anterior wall, 31%; posterior
      wall, 58%; greater curvature, 55%; and lesser curvature, 57%). CONCLUSION: We
      found that > 50% of the patients indicated for SN navigation surgery,
      particularly those with tumors in the upper third of the stomach, potentially
      could undergo partial resection with SNBD.

PMID- 30099637
TI  - Fidaxomicin for the treatment of Clostridium difficile infection (CDI) in at-risk
      patients with inflammatory bowel disease, fulminant CDI, renal impairment or
      hepatic impairment: a retrospective study of routine clinical use (ANEMONE).
AB  - Information is limited or lacking on fidaxomicin treatment of Clostridium
      difficile infection (CDI) in patients with inflammatory bowel disease, fulminant
      or life-threatening CDI, severe renal impairment, moderate-to-severe hepatic
      impairment and pregnancy. The ANEMONE study investigated fidaxomicin use in a
      routine clinical setting, focusing on these medical conditions of specific
      interest (MCSIs). This retrospective, post-authorisation study reviewed hospital
      records from Austria, Germany, Spain and the UK (June 2012-June 2015), collecting
      data from hospital admission to 30 days after last fidaxomicin dose. The primary
      objective was to identify the proportion of fidaxomicin-treated patients with
      MCSIs. Secondary objectives were to describe 30-day mortality, changes in ECG and
      laboratory parameters, fidaxomicin exposure and CDI response (resolution of
      diarrhoea; 30-day recurrence). 45.3% (261/576) of patients had >= 1 MCSI. Thirty
      day mortality (post-first dose) was 17.0% (98/576) in the total population and
      slightly higher (24.6-27.6%) in patients with fulminant CDI or severe renal
      impairment. 29.6% (24/81) deaths of known cause were attributable to CDI. Of
      changes in laboratory parameters or ECG findings, only a decrease in leucocyte
      counts appeared associated with fidaxomicin, consistent with a positive treatment
      response. Diarrhoea resolved in 78.0% (404/518) of treatment episodes; diarrhoea
      resolution was lowest in patients with fulminant CDI (investigator-defined,
      67.5%, 56/88) and severe renal impairment (68.0%, 68/100). Thirty-day recurrence
      (18.8%, 79/420) was similar across MCSI subgroups. Although almost half of
      fidaxomicin-treated patients had >= 1 MCSI, the majority of patients in all
      subgroups had positive responses to treatment, and no particular safety concerns
      were identified.

PMID- 30099638
TI  - A 5-year study of the performance of the Verigene Gram-positive blood culture
      panel in a pediatric hospital.
AB  - High accuracy of direct from positive blood culture molecular panels is
      imperative, particularly for the detection of resistance determinants as it
      allows for antimicrobial optimization prior to conventional susceptibility
      testing. In this study, we provide extensive data since implementation of the
      Verigene Gram-positive blood culture panel (BC-GP) in 2013. Within 5 years, 1636
      blood culture bottles positive for a Gram-positive organism were tested on the BC
      GP panel. The BC-GP panel identified 1520 Gram-positive organisms in 1636 (92.9%)
      blood cultures tested. For positive blood cultures, we observed 96.4% (806/834)
      concordance to the species level. Compared with conventional antimicrobial
      susceptibility testing, the positive percent agreement (PPA) of methicillin
      resistant SA (MRSA) (50) and methicillin-resistant SE (MRSE) (365) was 100%. The
      mecA gene was detected in two methicillin-susceptible Staphylococcus aureus
      (MSSA) and one methicillin-susceptible S. epidermidis (MSSE) with a negative
      percent agreement (NPA) of 99.1% (221/223) and 99.2% (120/121), respectively. The
      PPA and NPA for vancomycin-resistant Enterococcus faecium (VRE) was 100%. The BC
      GP panel demonstrated excellent performance and clinicians can confidently de
      escalate antimicrobial therapy in the absence of mecA and vanA/B gene.

PMID- 30099639
TI  - Morphometrics and Mitochondrial DNA Genes Analysis Suggest a New Species of
      Penaeus (Crustacea: Penaeidae) from the Persian Gulf.
AB  - There are two morphotypes of Penaeus semisulcatus described hitherto in the
      Persian Gulf, namely the banded and non-banded antennae morphotypes. In this
      study, we used morphometric measurements and two mitochondrial genes (16S rRNA
      and cytochrome oxidase subunit I-COI) to assess relationships between the two
      morphotypes of P. semisulcatus. Out of 25 morphological characters examined, 10
      characters were found significantly different between the two morphotypes when
      tested against separate sexes or both sexes combined. Results from the 16S rRNA
      and COI sequence analysis of two morphotypes of P. semisulcatus morphotype showed
      up to 6% and 17% sequence divergence, respectively. The 16S rDNA and COI
      sequences of the non-banding morphotype were not only very different to those of
      the banding morphotype but was also very different to all other Penaeus species
      (i.e., P. monodon, P. merguiensis, and P. indicus) included in the study. Both
      parsimony and Neighbor-Joining trees based on 16S rDNA and COI sequences provide
      similar tree topology that clearly separated the two morphotypes into two
      distinct groups. Based on these findings, we propose the two morphotypes of P.
      semisulcatus to be relegated as two sympatric species.

PMID- 30099640
TI  - A new esophageal elongation technique for long-gap esophageal atresia: in vitro
      comparison of myotomy techniques.
AB  - BACKGROUND: Complications such as stricture, leakage, recurrent tracheoesophageal
      fistula and mucosal pouch are commonly seen in myotomy techniques used for long
      gap esophageal atresia (LGEA) treatments. Therefore, we think that there is a
      clear need for other techniques which would enable us to create more robust and
      longer esophagus in such cases. In this study, we reviewed multiple V-myotomy
      (VM) technique and the differences of the said technique with Livaditis circular
      myotomy (LM) and Kimura spiral myotomy (KM) techniques using literature as an
      aid. METHODS: 21 esophagus samples from 21 male lambs aged 12 months were used in
      vitro for the study. All esophageal samples were matched to have a length of 120
      mm. Samples were divided into 3 groups of 7 and VM, LM and KM techniques were
      used in each group, respectively. Post-op esophagus lengths, elongation amount
      with each incision and perforation pressures were measured. RESULTS: Post-op
      esophageal lengths were measured as 227, 210 and 200 mm for VM, LM and KM,
      respectively. Elongation amount per incision was measured as 5.1, 4 and 3.34 mm,
      again in previous order of VM, LM, and KM. Finally, perforation pressure
      following VM, LM, and KM was measured as 460, 400, and 410 mmHg. CONCLUSION: VM
      was found to significantly increase total esophagus length and elongation per
      incision over LM and KM. In addition, VM was also shown to have a higher
      perforation pressure. Although in vivo live animal studies are required, we can
      say that VM can be used to create longer and robust esophagus.

PMID- 30099641
TI  - Denosumab does not decrease the risk of lung metastases from bone giant cell
      tumour.
AB  - PURPOSE: There are conflicting reports on the effect of denosumab on lung
      metastases in patients with giant cell tumor (GCT) of bone. To address these
      reports, we performed this study to determine if denosumab prevents lung
      metastasis and to evaluate univariate and multivariate predictors for lung
      metastases in these patients. MATERIALS AND METHODS: We retrospectively studied
      381 GCT patients with surgery alone and 30 GCT patients with surgery and
      denosumab administration. The median follow-up was 85.2 months (IQR, 54.2-124.4
      months). We evaluated lung metastases and local recurrences, univariate and
      multivariate predictors for lung metastases, response, and adverse events of
      denosumab administration. RESULTS: The occurrence of lung metastases was similar
      (surgery alone 4.7%, 18 patients; denosumab administration 3.3%, 1 patient);
      however, the occurrence of local recurrences was significantly higher in the
      patients with denosumab administration. Denosumab administration was not an
      important predictor for lung metastases; Campanacci stage and type of surgery
      were the only univariate predictors for lung metastases, and type of surgery and
      local recurrence were the only multivariate predictors for lung metastases.
      Histology showed viable tumour in all tumor specimens of the patients with
      denosumab administration. CONCLUSION: Denosumab does not decrease the risk of
      lung metastases in patients with bone GCT; the only important predictors for lung
      metastases in these patients are type of surgery and local recurrence. However,
      because the number of patients with lung metastases was small for a multivariate
      analysis, the possibility of denosumab's effect could not be completely
      eliminated.

PMID- 30099642
TI  - The influence of bearing surfaces on periprosthetic hip infections: analysis of
      thirty nine thousand, two hundred and six  cementless total hip arthroplasties.
AB  - PURPOSE: Periprosthetic hip infection (PHI) is a devastating complication. The
      association between PHI and bearing surfaces as well as patient-related factors
      has been recently investigated, with contradictive outcomes. The dataset of
      Emilia-Romagna region Registry for Orthopaedic Prosthetic Implants (RIPO) has
      been assessed to investigate, if the bearing choice influenced the risk of septic
      loosening occurrence. METHODS: RIPO data about 39,206 cementless total hip
      arthroplasties (THA), collected since 2003, were analysed. Age, gender, BMI,
      diabetes and bearing surfaces were evaluated. The end point of the study was the
      revision of at least a single component due to sepsis. RESULTS: Adjusted and
      unadjusted survival rates showed that ceramic-on-ceramic (COC) implants had the
      lower incidence of PHIs, whereas metal-on-metal (MOM) THAs were significantly
      more prone to infection. In MOM cohort, stemmed implants were involved in 28 out
      of 30 cases. Among the demographical features and comorbid conditions, only
      diabetes statistically influenced the rate of sepsis. CONCLUSIONS: Bearing
      surfaces influenced the rate of PHI; in particular, stemmed MOM implants were at
      higher risk, probably due to metal debris consequent to taperosis. Despite the
      preliminary results, stemmed MOM THAs should be used with care, and diabetic
      patients should be warned about increased septic risks.

PMID- 30099643
TI  - Curettage, phenolization, and cementation in paediatric Ewing's sarcoma with a
      complete radiological response to neoadjuvant chemotherapy.
AB  - PURPOSE: Although wide resection is the standard treatment for Ewing's sarcoma
      (ES), it has complications especially in children. In this study, we compared the
      oncologic and functional outcomes of wide resection with extended curettage and
      local adjuvant therapy (phenolization and cementation), as a less extensive
      surgery for paediatric ES with a complete radiologic response to neoadjuvant
      chemotherapy. METHODS: Children aged <= ten years, with ES of non-expendable long
      bones and complete radiologic response to neoadjuvant chemotherapy, were included
      in this case-control study. Twenty-six patients were treated with extended
      curettage and local adjuvant therapy (case group) and 17 were managed with wide
      resection (control group). The average follow-up period was 60.1 +/- 28.7 months
      (range 30-168 months). Functional outcome was assessed with the Musculoskeletal
      Tumor Society (MSTS) scoring system. RESULTS: Three local recurrences (11.5%) and
      three distant metastases (11.5%) were observed in the case group. Two local
      recurrences (11.7%) and two metastases (11.7%) were recorded in the control
      group. The rate of local recurrence was not statistically different between the
      two study groups (p = 0.668). The rate of metastasis was not statistically
      different between the two study groups as well (p = 0.668). The complication
      rates were 15% in the case group and 53% in the control group (p = 0.005). The
      mean MSTS score was 98.3% and 74% in the case and control group, respectively (p
      < 0.001). CONCLUSION: The oncologic outcome of extended curettage and local
      adjuvant therapy in paediatric ES with complete radiological response to
      neoadjuvant chemotherapy is comparable to wide resection, yet it offers
      considerably better functional results.

PMID- 30099645
TI  - Correction to: Rational design of engineered microbial cell surface multi-enzyme
      co-display system for sustainable NADH regeneration from low-cost biomass.
AB  - In the original publication, the author group has been published incorrectly. All
      authors have agreed to add Aihua Liu as co-author of this article, since the
      original idea for the experiments, the experimental expertise and some of the
      plasmids originated from him.

PMID- 30099644
TI  - A novel mutation in the PRPF31 in a North Indian adRP family with incomplete
      penetrance.
AB  - PURPOSE: To identify the underlying genetic defect for non-syndromic autosomal
      dominant retinitis pigmentosa (adRP) with incomplete penetrance in a North Indian
      family. METHODS: Family history and clinical data were collected. Linkage
      analysis using 72 fluorescently labeled microsatellite markers flanking all the
      26 candidate genes known for adRP was performed. Mutation screening in candidate
      gene at the mapped region was performed by bi-directional DNA sequencing.
      RESULTS: Positive two-point lod scores > 1.0 (theta = 0.000) suggestive of
      linkage were obtained with markers D19S572, D19S927 and D19S926 at 19q13.42, in
      the vicinity of PRPF31 gene. Mutation screening in all the 14 exonic regions and
      intron-exon boundaries of PRPF31 revealed a novel change, i.e. c.896G>A
      (p.Cys299Tyr) in exon eight. The observed change segregated in heterozygous form
      in all the six affected members and in three carriers, consistent with incomplete
      penetrance. This substitution was not observed in tested 15 unaffected members
      and in 200 ethnically matched controls. CONCLUSION: Present study describes
      mapping of a locus for non-syndromic adRP with incomplete penetrance at 19q13.42
      in a North Indian family and identifies a novel missense mutation (p.Cys299Tyr)
      in PRPF31 localized at the mapped interval. The observed substitution lies in the
      NOP domain of PRPF31 that exhibit RNA and protein binding surfaces and thus may
      interfere in the formation of spliceosome complex. Due to p.Cys299Tyr
      substitution hydrogen bonds are generated, which may result in conformational
      changes and PRPF31 protein deformity. Present findings further substantiate the
      role of PRPF31 in adRP with incomplete penetrance and expand the mutation
      spectrum of PRPF31.

PMID- 30099647
TI  - Music Therapy for Coping Self-Efficacy in an Acute Mental Health Setting: A
      Randomized Pilot Study.
AB  - For adults with mental illness, coping skills represent an integral component of
      illness management and recovery (IMR) programs. Music therapy can be used to
      target IMR but empirical research specific to coping is needed. The purpose of
      this study was to determine if educational music therapy can influence coping
      self-efficacy in acute care mental health inpatients. Adults on an acute care
      mental health unit (N = 92) were cluster-randomized to one of three single
      session conditions over 24 group-based sessions: educational lyric analysis,
      educational songwriting, or control. Although results were not significant, both
      educational music therapy conditions tended to have more favorable coping self
      efficacy subscale means than the control condition but there were negligible
      differences between lyric analysis and songwriting conditions. Results can be
      considered clinically relevant within the temporal parameters of single-session
      therapy typical in acute care settings. Limitations, implications for practice,
      and suggestions for future research are included.

PMID- 30099648
TI  - Who Becomes a Bullying Perpetrator After the Experience of Bullying
      Victimization? The Moderating Role of Self-esteem.
AB  - It is well known that victims of bullying could become a bullying perpetrator
      later on. However, there are some cases where victims do not become bullies after
      being bullied. What constitutes the differences between the two groups, who show
      different response strategies despite the similar experiences of victimization,
      is the main question that the current study poses. Based on the threatened
      egotism theory, the current longitudinal study postulates that there could be
      possible moderating effects of self-esteem in the relationship between prior
      bullying victimization and subsequent bullying perpetration. The data was drawn
      from 3,660 Korean secondary students (51.5% male) in the Seoul Education
      Longitudinal Study for 2 waves (7th to 8th grades). The results from structural
      equation modeling indicated that there is a significant interaction effect
      between bullying victimization and self-esteem in the 7th grade, in prediction to
      bullying perpetration in the 8th grade, after controlling for the prior level of
      bullying victimization and perpetration experiences, demographic and background
      characteristics (i.e., gender and family income), students' school-environmental
      factor (i.e., perceived seriousness of school bullying), individual factor (i.e.,
      self-control) and family-environmental factor (i.e., parent-child relationship).
      Students with higher self-esteem were the most likely to engage in future
      bullying perpetration in response to bullying victimization, while the students
      with lower self-esteem were the least likely to engage in future bullying
      perpetration. Educators who examine adolescents' social problems should pay
      closer attention to self-esteem, as well as their bullying and victimization
      experiences, in order to provide appropriate interventions.

PMID- 30099646
TI  - Electrical manipulation of the failing heart.
AB  - Chronic heart failure with reduced (<= 40%) ejection fraction (HFrEF) poses a
      significant residual mortality risk despite modern optimal medical therapy. In
      the last decades, we have witnessed the introduction of breakthrough cardiac
      implantable electronic devices (CIED) aimed at addressing sudden cardiac death
      and HF progression in patients with HFrEF, leading to improved survival and
      functional capacity. Following their introduction, implantable cardioverter
      defibrillators (ICD) and cardiac resynchronization therapy (CRT) have undergone
      substantial technological improvements and have been investigated in different
      settings of HFrEF, some of which yielded controversial results. In this review,
      we provide a comprehensive, yet pragmatic, approach to the individual key points
      in the electrical manipulation of the failing heart with ICD and CRT including
      patient selection, technological advances in the implant technique, follow-up,
      and long-term management. The aim of the review is to provide real-life-oriented
      advices to maximize the desired outcomes of CIED-based therapy of HFrEF.
      Accordingly, a framework to inform the decision-making process in candidates to
      ICD and/or CRT has been developed reflective of a critical appraisal of the most
      recently available evidence reappraising some domains beyond the classic views.

PMID- 30099649
TI  - Androgen Receptor Signalling Promotes a Luminal Phenotype in Mammary Epithelial
      Cells.
AB  - Androgens influence mammary gland development but the specific role of the
      androgen receptor (AR) in mammary function is largely unknown. We identified cell
      subsets that express AR in vivo and determined the effect of AR activation and
      transgenic AR inhibition on sub-populations of the normal mouse mammary
      epithelium by flow cytometry and immunohistochemistry. Immunolocalisation of AR
      with markers of lineage identity was also performed in human breast tissues. AR
      activation in vivo significantly decreased the proportion of basal cells, and
      caused an accumulation of cells that expressed a basal cell marker but exhibited
      morphological features of luminal identity. Conversely, in AR null mice the
      proportion of basal mammary epithelial cells was significantly increased.
      Inhibition of AR increased basal but not luminal progenitor cell activity in
      vitro. A small population of AR-positive cells in a basal-to-luminal phenotype
      transition was also evident in human breast lobules. Collectively, these data
      support a role for AR in promoting a luminal phenotype in mammary epithelial
      cells.

PMID- 30099650
TI  - AgMYB2 transcription factor is involved in the regulation of anthocyanin
      biosynthesis in purple celery (Apium graveolens L.).
AB  - MAIN CONCLUSION: This study showed that an R2R3-MYB transcription factor, AgMYB2,
      functions in anthocyanin biosynthesis and accumulation in purple celery.
      Anthocyanins are involved in tissue coloration and stress response in plants.
      Foods containing high anthocyanin content are also beneficial to human health.
      Purple celery accumulated amounts of anthocyanins in the petioles. The
      biosynthesis of anthocyanin in plants is mainly regulated by the R2R3-MYB
      transcription factor (TF). However, the R2R3-MYB TF that controls anthocyanin
      accumulation in purple celery remains unclear. In this study, an R2R3-MYB TF
      gene, AgMYB2, was cloned from purple celery and characterized as anthocyanin
      biosynthetic regulator. Sequence analysis indicated that AgMYB2 contained highly
      conserved R2R3 domain and two anthocyanin characteristic motifs, ANDV motif and
      KPRPR[S/T]F motif. The relative expression level of AgMYB2 in purple celery was
      significantly higher than that in non-purple celery at three developmental
      stages. Heterologous expression of AgMYB2 in Arabidopsis generated more
      anthocyanins and resulted in dark-purple leaves and flowers. The expression
      levels of anthocyanin biosynthetic genes and the antioxidant activity of
      transgenic Arabidopsis carrying AgMYB2 were up-regulated. The determination of
      anthocyanin glycosylation activity of Arabidopsis crude enzyme verified the
      anthocyanin biosynthesis regulatory function of AgMYB2 at the protein level. The
      interaction between AgMYB2 and bHLH proteins was shown by yeast two-hybrid assay.
      The results will help to elucidate the molecular mechanism of anthocyanin
      biosynthesis in purple celery and provide an approach for cultivating plants with
      high anthocyanin content.

PMID- 30099651
TI  - Evidence for preservation of vacuolar compartments during foehn-induced chalky
      ring formation of Oryza sativa L.
AB  - MAIN CONCLUSION: Vacuolar compartments being sustained among the amyloplasts
      inadequately accumulated in rice endosperm cells are the main cause of chalky
      ring formation under dry wind conditions. Foehn-induced dry wind during the grain
      filling stage induces shoot water deficit in rice (Oryza sativa L.) plants, which
      form a ring-shaped chalkiness in their endosperm that degrades milling quality
      and rice appearance. Air spaces formed in several inner cells cause significant
      transparency loss due to irregular light reflection. Although starch synthesis
      was suggested to be retarded by osmotic adjustment at foehn-induced moderately
      low water potential, the source of these air spaces remains unknown. We
      hypothesised that the preservation of vacuoles accompanied by a temporary
      reduction in starch biosynthesis in the inner cells leads to the chalky ring
      formation. Panicle water status measurement, light and transmission electron
      microscopic (TEM) observations, and an absolute qPCR analysis were conducted.
      Most starch synthesis-related genes exhibited temporarily reduced expression in
      the inner zone in accordance with the decrease in panicle water status. TEM
      observations provided evidence that vacuolar compartments remained among the
      loosely packed starch granules in the inner endosperm cells, where a chalky ring
      appeared after kernel dehydration. Taken together, we propose that vacuolar
      compartments sustained among the amyloplasts inadequately accumulated in rice
      endosperm cells and caused air space formation that leads to ring-shaped
      chalkiness under dry wind conditions.

PMID- 30099652
TI  - Effects of Probiotics on Inflammation and Uremic Toxins Among Patients on
      Dialysis: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND/OBJECTIVES: We performed this systematic review and meta-analysis to
      evaluate effects of probiotics on inflammation, uremic toxins, and
      gastrointestinal (GI) symptoms in end-stage renal disease (ESRD) patients.
      METHODS: A literature search was conducted utilizing MEDLINE, EMBASE, and
      Cochrane Database from inception through October 2017. We included studies that
      assessed assessing effects of probiotics on inflammatory markers, protein-bound
      uremic toxins (PBUTs), and GI symptoms in ESRD patients on dialysis. Effect
      estimates from the individual study were extracted and combined utilizing random
      effect, generic inverse variance method of DerSimonian and Laird. The protocol
      for this meta-analysis is registered with PROSPERO; No. CRD42017082137. RESULTS:
      Seven clinical trials with 178 ESRD patients were enrolled. There was a
      significant reduction in serum C-reactive protein (CRP) from baseline to post
      probiotic course (>= 2 months after treatment) with standardized mean difference
      (SMD) of - 0.42 (95% CI - 0.68 to - 0.16, p = 0.002). When compared to control,
      patients who received probiotics also had a significant higher degree of
      reduction in CRP level with SMDs of - 0.37 (95% CI - 0.72 to 0.03, p = 0.04).
      However, there were no significant changes in serum TNF-alpha or albumin with
      SMDs of - 0.32 (95% CI - 0.92 to 0.28, p = 0.29) and 0.16 (95% CI - 0.20 to 0.53,
      p = 0.39), respectively. After probiotic course, there were also significant
      decrease in PBUTs and improvement in overall GI symptoms (reduction in GI symptom
      scores) with SMDs of - 0.61 (95% CI - 1.16 to - 0.07, p = 0.03) and - 1.04 (95%
      CI - 1.70 to - 0.38, p = 0.002), respectively. CONCLUSION: Our study demonstrates
      potential beneficial effects of probiotics on inflammation, uremic toxins, and GI
      Symptoms in ESRD patients. Future large-scale clinical studies are required to
      assess its benefits on other important clinical outcomes including patient
      mortality.

PMID- 30099653
TI  - 2D MoSe2 sheets embedded over a high surface graphene hybrid for the amperometric
      detection of NADH.
AB  - Delaminated 2D sheets of MoSe2 were prepared by liquid phase exfoliation and were
      embedded over high surface area hydrogen exfoliated graphene (HEG) by a simple
      technique. The MoSe2/HEG hybrid composite exhibits fast heterogeneous electron
      transfer (HET) and a high electrochemically active surface area compared to only
      HEG. When employed for detection of NADH, it exhibits electrooxidation at a low
      potential of 150 mV (vs. Ag/AgCl) with high sensitivity of 0.0814 uA?uM-1?cm2
      over a wide linear range (1-280 MUM), good selectivity, and a low limit of
      detection (1 MUM). The good performance of the composite is due to the
      homogeneously dispersed 2D sheets of MoSe2 over large-surface area HEG, which
      retain its electrochemical activity, prevents restacking, and acts as an electron
      transfer channel. On the basis of the above analytical requirements and its easy
      synthesis, the hybrid composite represents a robust material for electrochemical
      sensing. Graphical abstract Schematic of the 2D MoSe2/HEG composite for
      electrochemical detection of NADH.

PMID- 30099654
TI  - Added value of non-criteria antiphospholipid antibodies for antiphospholipid
      syndrome: lessons learned from year-long routine measurements.
AB  - The international classification criteria for definite antiphospholipid syndrome
      (APS) include three laboratory measurements: lupus anticoagulant (LA), IgG and
      IgM isotypes of anti-cardiolipin (aCL) and anti-beta2glycoprotein I antibodies
      (anti-beta2GPI). When persistently elevated, they are specific for APS; however,
      many patients that fulfil clinical criteria may exhibit negative serological
      results. These "seronegative" APS (SN-APS) are exposed to an increased thrombotic
      risk. The aims of our cross-sectional, retrospective study of consecutive
      autoimmune patients' samples were to evaluate the association of non-criteria
      antiphospholipid antibodies (aPL) with thrombosis and obstetric events, to
      calculate the risk score for adverse events and to assess the specific
      contribution of single aPL positivity in SN-APS. LA, aCL, anti-beta2GPI and anti
      phosphatidylserine/prothrombin antibodies (aPS/PT) of IgG, IgM, and IgA isotypes
      were determined in sera of 323 patients with autoimmune disorders. Medical
      records of all patients were carefully analyzed. aCL, anti-beta2GPI and aPS/PT of
      IgG and IgA isotypes were significantly associated with thrombosis while none of
      the IgM aPL showed such association. aPS/PT of all isotypes, aCL and anti
      beta2GPI of IgG and IgA isotype showed significant correlation to obstetric
      events. When considering results of aPS/PT ELISA, we could additionally identify
      3% of thrombotic patients and 2% of obstetric patients. Thrombotic and obstetric
      risk scores were calculated showing significantly higher association to clinical
      events, as compared to evaluating individual risk factors. aPS/PT could represent
      an additional biomarker in SN-APS patients. IgA aPL are associated with
      thrombosis and obstetric complications. Risk scores accounting different aPL and
      conventional risk factors, better assesses risk for adverse event, as compared to
      evaluating individual factors alone.

PMID- 30099656
TI  - A Comparison Between Two Screening Approaches for ASD Among Toddlers in Israel.
AB  - Systematic screening of autism spectrum disorder (ASD) can improve early
      diagnosis of ASD. We compared the efficacy of two ASD screening methods, the
      Global Developmental Screening (GDS), and the Modified Checklist for Autism in
      Toddlers-Revised, with Follow-Up (M-CHAT/F) in 1591 toddlers of ages 18-36 months
      from 35 government-funded clinics in south Israel. The M-CHAT/F performed better
      than the GDS in detecting toddlers with ASD (sensitivity: 70.0% vs. 50.0%, and
      specificity: 98.2% vs. 96.6% respectively). Both methods had an equivalent
      performance in detecting other forms of developmental delays (sensitivity = 63%;
      and specificity ~ 98%). In addition, remarkable inter-nurse variation was
      observed in the GDS referral decisions. Thus, employment of the M-CHAT/F in the
      Israeli health system may improve early detection of ASD among toddlers.

PMID- 30099655
TI  - Comparative efficacy between adalimumab and infliximab in the treatment of non
      infectious intermediate uveitis, posterior uveitis, and panuveitis: a
      retrospective observational study of 107 patients.
AB  - To compare the efficacy of adalimumab (ADA) and infliximab (IFX) in patients with
      non-infectious intermediate uveitis, posterior uveitis, and panuveitis.
      Demographic, clinical, instrumental, and therapeutic data from patients enrolled
      were collected at the start of treatment, at 12-month follow-up, and at the last
      follow-up assessment. One hundred seven patients (46 females, 187 eyes) were
      enrolled, 66 (61.7%) treated with ADA and 41 (38.3%) with IFX. Bilateral
      involvement was observed in 80 cases. The mean follow-up was 26.45 +/- 21.71
      months for ADA patients and 56.60 +/- 56.04 months for IFX patients. The overall
      decrease of uveitis frequency during the first 12 months of treatment was 66.7%
      in the IFX group and 84.2% in the ADA group, compared to the previous 12 months
      (p = 0.09). A significantly higher corticosteroid dosage was found among patients
      treated with ADA at the last follow-up visit (p = 0.008). The percentage of
      patients co-administered with corticosteroids was significantly higher among ADA
      patients both at the 12-month visit (p = 0.03) and at the last visit (p =
      0.0004). The frequency of uveitic macular edema (UME) was significantly higher
      among patients treated with ADA compared to those treated with IFX at the 12
      month assessment (p = 0.015) and at the last follow-up visit (p = 0.011); central
      macular thickness was significantly higher in ADA group compared to the IFX group
      at the last follow-up assessment (p = 0.04). ADA and IFX have shown a similar
      efficacy in controlling uveitis relapses, but IFX showed a more pronounced
      corticosteroid sparing effect and a significantly higher capacity in resolving
      UME compared to ADA.

PMID- 30099657
TI  - Evolutionary tinkering vs. rational engineering in the times of synthetic
      biology.
AB  - Synthetic biology is not only a contemporary reformulation of the recombinant DNA
      technologies of the last 30 years, combined with descriptive language imported
      from electrical and industrial engineering. It is also a new way to interpret
      living systems and a statement of intent for the use and reprogramming of
      biological objects for human benefit. In this context, the notion of designer
      biology is often presented as opposed to natural selection following the powerful
      rationale formulated by Francois Jacob on evolution-as-tinkering. The onset of
      synthetic biology opens a different perspective by leaving aside the question
      about the evolutionary origin of biological phenomena and focusing instead on the
      relational logic and the material properties of the corresponding components that
      make biological system work as they do. Once a functional challenge arises, the
      solution space for the problem is not homogeneous but it has attractors that can
      be accessed either through random exploration (as evolution does) or rational
      design (as engineers do). Although these two paths (i.e. evolution and
      engineering) are essentially different, they can lead to solutions to specific
      mechanistic bottlenecks that frequently coincide or converge-and one can easily
      help to understand and improve the other. Alas, productive discussions on these
      matters are often contaminated by ideological preconceptions that prevent
      adoption of the engineering metaphor to understand and ultimately reshape living
      systems-as ambitioned by synthetic biology. Yet, some possible ways to overcome
      the impasse are feasible. In parallel to Monod's evolutionary paradox of teleo
      logy (finality/purpose) vs. teleo-nomy (appearance of finality/purpose), a
      mechanistic paradox could be entertained between techno-logy (rational
      engineering) vs techno-nomy (appearance of rational engineering), all for the
      sake of understanding the relational logic that enables live systems to function
      as physico-chemical entities in time and space. This article thus proposes a
      radical vision of synthetic biology through the lens of the engineering metaphor.

PMID- 30099659
TI  - Accuracy assessment of wireless transponder tracking in the operating room
      environment.
AB  - PURPOSE: To evaluate the applicability of the Calypso(r) wireless transponder
      tracking system (Varian Medical Systems Inc., USA) for real-time tumor motion
      tracking during surgical procedures on tumors in non-rigid target areas. An
      accuracy assessment was performed for an extended electromagnetic field of view
      (FoV) of 27.5 * 27.5 * 22.5 cm (which included the standard FoV of 14 * 14 * 19
      cm) in which 5DOF wireless Beacon(r) transponders can be tracked. METHODS: Using
      a custom-made measurement setup, we assessed single transponder relative
      accuracy, absolute accuracy and jitter throughout the extended FoV at 1440
      locations interspaced with 2.5 cm in each orthogonal direction. The NDI Polaris
      Spectra optical tracking system (OTS) was used as a reference. Measurements were
      taken in a room without surrounding distorting factors and repeated in an
      operating room (OR). In the OR, the influence of a carbon fiber and regular
      stainless steel OR tabletop was investigated. RESULTS: The calibration of the OTS
      and transponder system resulted in an average root-mean-square error (RMSE)
      vector of 0.03 cm. For both the standard and extended FoV, all accuracy measures
      were dependent on transponder to tracking array (TA) distances and the absolute
      accuracy was also dependent on TA to OR tabletop distances. This latter influence
      was reproducible, and after calibrating this, the residual error was below 0.1 cm
      RMSE within the entire standard FoV. Within the extended FoV, this residual RMSE
      did not exceed 0.1 cm for transponder to TA distances up to 25 cm. CONCLUSION:
      This study shows that transponder tracking is promising for accurate tumor
      tracking in the operating room. This applies when using the standard FoV, but
      also when using the extended FoV up to 25 cm above the TA, substantially
      increasing flexibility.

PMID- 30099658
TI  - Elevated hydrostatic pressure stimulates ATP release which mediates activation of
      the NLRP3 inflammasome via P2X4 in rat urothelial cells.
AB  - Partial bladder outlet obstruction (pBOO) is a prevalent urological condition
      commonly accompanied by increased intravesical pressure, inflammation, and
      fibrosis. Studies have demonstrated that pBOO results in increased NLRP3
      inflammasome and caspase-1 activation and that ATP is released from urothelial
      cells in response to elevated pressure. In the present study, we investigated the
      role of elevated pressure in triggering caspase-1 activation via purinergic
      receptors activation in urothelial cells. Rat urothelial cell line, MYP3 cells,
      was subjected to hydrostatic pressures of 15 cmH2O for 60 min, or 40 cmH2O for 1
      min to simulate elevated storage and voiding pressure conditions, respectively.
      ATP concentration in the supernatant media and intracellular caspase-1 activity
      in cell lysates were measured. Pressure experiments were repeated in the presence
      of antagonists for purinergic receptors to determine the mechanism for pressure
      induced caspase-1 activation. Exposure of MYP3 cells to both pressure conditions
      resulted in an increase in extracellular ATP levels and intracellular caspase-1
      activity. Treatment with P2X7 antagonist led to a decrease in pressure-induced
      ATP release by MYP3 cells, while P2X4 antagonist had no effect but both
      antagonists inhibited pressure-induced caspase-1 activation. Moreover, when MYP3
      cells were treated with extracellular ATP (500 uM), P2X4 antagonist inhibited ATP
      induced caspase-1 activation, but not P2X7 antagonist. We concluded that pressure
      induced extracellular ATP in urothelial cells is amplified by P2X7 receptor
      activation and ATP-induced-ATP release. The amplified ATP signal then activates
      P2X4 receptors, which mediate activation of the caspase-1 inflammatory response.

PMID- 30099660
TI  - Development of a shoulder-mounted robot for MRI-guided needle placement: phantom
      study.
AB  - PURPOSE: This paper presents new quantitative data on a signal-to-noise ratio
      (SNR) study, distortion study, and targeting accuracy phantom study for our
      patient-mounted robot (called Arthrobot). Arthrobot was developed as an MRI
      guided needle placement device for diagnostic and interventional procedures such
      as arthrography. METHODS: We present the robot design and inverse kinematics.
      Quantitative assessment results for SNR and distortion study are also reported. A
      respiratory motion study was conducted to evaluate the shoulder mounting method.
      A phantom study was conducted to investigate end-to-end targeting accuracy.
      Combined error considering targeting accuracy, respiratory motion, and structure
      deformation is also reported. RESULTS: The SNR study showed that the SNR changes
      only 2% when the unpowered robot was placed on top of a standard water phantom.
      The distortion study showed that the maximum distortion from the ground truth was
      2.57%. The average error associated with respiratory motion was 1.32 mm with
      standard deviation of 1.38 mm. Results of gel phantom targeting studies indicate
      average needle placement error of 1.64 mm, with a standard deviation of 0.90 mm.
      CONCLUSIONS: Noise and distortion of the MR images were not significant, and
      image quality in the presence of the robot was satisfactory for MRI-guided
      targeting. Combined average total error, adding mounting stability errors and
      structure deformation errors to targeting error, is estimated to be 3.4 mm with a
      standard deviation of 1.65 mm. In clinical practice, needle placement accuracy
      under 5 mm is considered sufficient for successful joint injection during
      shoulder arthrography. Therefore, for the intended clinical procedure, these
      results indicate that Arthrobot has sufficient positioning accuracy.

PMID- 30099661
TI  - Role of lipoprotein (a) and LPA KIV2 repeat polymorphism in bicuspid aortic valve
      stenosis and calcification: a proof of concept study.
AB  - Hemodynamic valvular impairment is a frequent determinant of the natural history
      of bicuspid aortic valve (BAV). The role of elevated Lp(a) levels and LPA Kringle
      IV type 2 (KIV-2) size polymorphism in influencing aortic valve calcification and
      stenosis development in patients with tricuspid aortic valve was recognized. In
      this study, we investigate the association between Lp(a) and LPA KIV-2 repeat
      number, and the presence of calcification and stenosis in BAV patients. Sixty
      nine patients [79.7% males; median age 45(30-53) yrs], consecutively referred to
      Center for Cardiovascular Diagnosis or Referral Center for Marfan syndrome or
      related disorders, AOU Careggi, from June to November 2014, were investigated.
      For each patient, clinical (ECG and echocardiography) and laboratory [Lp(a)
      (Immunoturbidimetric assay) and LPA KIV-2 repeat number (real-time PCR)]
      evaluation were performed. Patients were compared with 69 control subjects. No
      significant association between Lp(a) circulating levels and LPA KIV-2 repeat
      number and BAV was evidenced. Among BAV patients, significantly higher Lp(a)
      levels according to calcification degree were found [no calcifications:78(42-159)
      mg/L, mild/moderate: 134(69-189) mg/L; severe: 560(286-1511) mg/L, p = 0.008].
      Conversely, lower LPA KIV-2 repeat numbers in subjects with more severe
      calcification degree were observed. Furthermore, higher Lp(a) levels in patients
      with aortic stenosis [214(67-501) mg/L vs 104(56-169) mg/L, p = 0.043] were also
      found. In conclusion, present data suggest the potential role for Lp(a) as a
      possible risk marker useful to stratify, among BAV patients, those with a higher
      chance to develop valvular calcifications and aortic stenosis.

PMID- 30099663
TI  - Low confidence levels with the robotic platform among senior surgical residents:
      simulation training is needed.
AB  - Acquisition of robotic surgical skills by surgical residents is usually hindered
      by time pressure and financial imperatives. Robotic simulation training offers an
      attractive solution because it allows residents to learn in a safe, controlled,
      and standardized environment. We aimed to determine the confidence levels of
      senior surgical residents with the robotic platform, and how those levels were
      affected by simulation training. Twenty senior residents participated in a
      simulation course using perfused porcine tissue blocks to perform the following
      robotic procedures: Nissen fundoplication, Heller myotomy, sleeve gastrectomy,
      colectomy, and lobectomy. Procedural steps evaluated included port placements,
      docking process, suturing, using energy devices, and using staplers. Mean
      baseline confidence levels were low for all the surgical steps analyzed, and all
      these values significantly increased after the 3-day robotic training in the
      simulation center. A standardized formal robotic simulation program with
      realistic hands-on training should be incorporated in the general surgery
      residency curriculum.

PMID- 30099662
TI  - Association of individual and area-level socioeconomic conditions with quality of
      life and glycaemic control in 11- to 21-year-old adolescents with early-onset
      type 1 diabetes: a cross-sectional study.
AB  - PURPOSE: To analyse the association of area-level deprivation (German Index of
      Multiple Deprivation, GIMD 2010) with health- and disease-related quality of life
      (QoL) and glycaemic control (HbA1c) jointly with individual-level socioeconomic
      status (SES) in young patients with preschool-onset type 1 diabetes. METHODS: A
      total of 425 male and 414 female patients aged 11-21 years from a Germany-wide
      population-based survey completed the generic KINDL-R, the DISABKIDS chronic
      generic module (DCGM-12), and the DISABKIDS diabetes-specific module with impact
      and treatment scales (QoL indicators; range 0-100 with higher scores representing
      better QoL). To analyse the association of area-level deprivation and SES with
      QoL and HbA1c, multiple linear regression models were applied adjusting for
      sociodemographic and health-related variables. RESULTS: Mean QoL scores (SD) were
      73.2 (12.2) for the KINDL-R, 76.1 (16.1) for the DCGM-12, 66.2 (19.9) for
      diabetes impact, and 56.4 (27.3) for diabetes treatment (DISABKIDS). Mean HbA1c
      was 8.3 (1.4)%. While both QoL outcomes and HbA1c level improved with increasing
      individual SES, no association was observed between area-level deprivation (GIMD
      2010) and either outcome. CONCLUSIONS: Compared with individual SES, area-level
      deprivation seems to be of minor importance for QoL and glycaemic control in
      young people with early-onset type 1 diabetes.

PMID- 30099665
TI  - Risk of Colorectal Polyps and Malignancies Among Predominantly Rural Hispanics.
AB  - Colorectal cancer is the fourth most frequently diagnosed cancer. However, due to
      variations in diet, it was hypothesized that risk of adenomatous or hyperplastic
      polyps or malignancies would be lower among Hispanics. Participants (n = 1671)
      underwent a colonoscopy. Results were grouped into one of four groups: normal,
      hyperplastic polyps only, adenomatous polyps, and malignancies. As expected,
      Hispanics had a lower risk of hyperplastic (p = .031, OR = 0.47) and adenomatous
      polyps (p = .031, OR = 0.66) than non-Hispanic Whites. Comparison between
      malignancies was not possible as no Hispanics had a malignancy. Contrary to
      expectations, risk of hyperplastic and adenomatous polyps and malignancies were
      no different between non-Hispanic Blacks and Whites. Among rural and mostly rural
      populations, Hispanics had a lower risk of hyperplastic and adenomatous polyps.

PMID- 30099667
TI  - The spectrum of end of life care: an argument for access to medical assistance in
      dying for vulnerable populations.
AB  - Medical assistance in dying (MAiD) was legalized by the Supreme Court of Canada
      in June 2016 and became a legal, viable end of life care (EOLC) option for
      Canadians with irremediable illness and suffering. Much attention has been paid
      to the balance between physicians' willingness to provide MAiD and patients'
      legal right to request medically assisted death in certain circumstances. In
      contrast, very little attention has been paid to the challenge of making MAiD
      accessible to vulnerable populations. The purpose of this paper was to examine
      the extant literature and resources that are available on the provision of MAiD
      in Canada. We found that the provision of EOLC in Canada offers insufficient
      access to palliative and EOLC options for Canadians and that vulnerable Canadians
      experience disproportional barriers to accessing these already limited resources.
      Consequently, we argue that palliative care, hospice care and MAiD must be
      considered a spectrum of EOLC that is inclusive and accessible to all Canadians.
      We conclude by imploring Canadian healthcare professionals, policy makers and
      legislators to consider MAiD as a viable EOLC option for all Canadians.

PMID- 30099664
TI  - PharmAdhere: training German community pharmacists with Objective Structured
      Clinical Examinations.
AB  - Background Pharmacists who engage in Pharmaceutical Care need skills to optimise
      responsible medication use and increase medication adherence. Objectives We
      developed and evaluated a blended-learning programme for German community
      pharmacists that focused on conducting consultations in chronic diseases. Setting
      Community pharmacists in Germany. Method Interventional study with pre-post
      design. We combined e-learning with Objective Standardised Clinical Examinations
      (OSCEs) for emergency situations, initiation/implementation of medication therapy
      and detection of symptoms of four chronic diseases. Specific procedures were
      defined in the Pharmaceutical Action Plan. Skills were measured with a global
      analytical marking sheet derived from the Medication Related Consultation
      Framework and scored with the Canadian criticality/relevancy matrix. Time limits
      matched real practice scenarios. Main outcome measures Changes in knowledge
      (difference of test results before and after e-learning) and changes in skills
      (difference in scores of the OSCEs before and after training). Results 22 out of
      the 26 pharmacists enrolled, completed the study. The number of correctly
      answered questions increased significantly after the e-learning for all four
      indications with a mean number of additional correct answers between 3.86 and 4.9
      points out of 15 (p < 0.001). The sums of the analytical checklist points in
      percentages increased significantly in all topics from the baseline summative
      OSCE to the final summative OSCE between 6.14 and 31.85% (p < 0.001). The maximum
      duration of consultation per patient was less than 10 min in all OSCEs.
      Conclusion The use of e-learning and OSCEs was well received by participants and
      is a successful method to deliver practical Pharmaceutical Care training.

PMID- 30099666
TI  - Expression of BMP2/4/7 during the odontogenesis of deciduous molars in miniature
      pig embryos.
AB  - Bone morphogenetic proteins (BMPs) play important roles in tooth development.
      However, their expression has not been studied in miniature pigs, which have many
      anatomical similarities in oral and maxillofacial region compared to human. This
      study investigated BMP2/4/7 expression patterns during deciduous molar
      development in miniature pigs on embryonic days (E) 40, 50, and 60. The mandibles
      were fixed, decalcified, and embedded before sectioning. H&E staining,
      immunohistochemistry, in situ hybridization using specific radionuclide-labeled
      cRNA probes, and real-time PCR were used to detect the BMP expression patterns
      during morphogenesis of the third deciduous molar. H&E staining showed that for
      the deciduous third molar, E40 represented the cap stage, E50 represented the
      early bell stage, and E60 represented the late bell stage or secretory stage.
      BMP2 was expressed in both the enamel organ and in the dental mesenchyme on E40
      and E50 and was expressed mainly in pre-odontoblasts on E60. BMP7 expression was
      similar to BMP2 expression, but BMP7 was also expressed in the inner enamel
      epithelium on E60. On E40, BMP4 was expressed mainly in the epithelium, with some
      weak expression in the mesenchyme. On E50, BMP4 expression was stronger in the
      mesenchyme but weaker in the epithelium. On E60, BMP4 was expressed mainly in the
      mesenchyme. These data indicated that BMP2/4/7 showed differential spatial and
      temporal expression during the morphogenesis and odontogenesis of deciduous
      molars, suggesting that these molecules were associated with tooth morphogenesis
      and cell differentiation.

PMID- 30099668
TI  - Is vertebral body stenting in combination with CaP cement superior to
      kyphoplasty?
AB  - PURPOSE: In the evolution of the minimally invasive treatment of vertebral
      compression fractures, vertebral body stenting (VBS) was developed to reduce
      intraoperative and secondary loss of vertebral height. Particularly in
      combination with the usage of biodegradable cement, the influence of VBS on the
      rate of intraoperative complications and long-term outcome is unclear. The
      purpose of this study was to investigate the differences between balloon
      kyphoplasty (BKP) and VBS regarding their long-term clinical and radiological
      outcome in combination with calcium phosphate (CaP) application instead of
      polymethyl methacrylate (PMMA). METHODS: This retrospective study included 49
      patients with fresh mono-segmental thoracolumbar fractures without neurological
      signs treated with VBS or BKP and CaP cement (Calcibone). The outcome was
      evaluated with the visual analogue pain scale (VAS), the Oswestry disability
      score (ODI), and radiologically assessed. RESULTS: In the course of the
      radiological follow-up, the VBS group showed statistically significant less
      vertebral height loss than the BKP group. However, with respect to VAS and ODI
      scores there were no statistically significant differences between the VBS and
      BKP group in the clinical follow-up. The rate of cement leakage was comparable in
      both groups. CONCLUSIONS: Both techniques facilitated good clinical results in
      combination with absorbable cement augmentation. In particular, the VBS enabled
      us to benefit from the advantages of the resorbable isothermic CaP cement with an
      improved radiological outcome in the long term compared to BKP. However, there
      was a mentionable loss of reduction in the follow-up in both groups compared to
      previously published data with PMMA cement. These slides can be retrieved under
      Electronic Supplementary Material.

PMID- 30099670
TI  - Minimally invasive spinal decompression surgery in diabetic patients:
      perioperative risks, complications and clinical outcomes compared with non
      diabetic patients' cohort.
AB  - BACKGROUND: Prior studies have documented an increased complication rate in
      diabetic patients undergoing spinal surgery. However, the impact of diabetes on
      the risk of postoperative complications and clinical outcome following minimally
      invasive spinal (MIS) decompression is not well understood. OBJECTIVES: To
      compare complication rates and outcomes of MIS decompression in diabetic patients
      with a cohort of non-diabetic patients undergoing similar procedures. METHODS:
      Medical records of 48 patients with diabetes and 151 control patients that
      underwent minimally invasive lumbar decompression between April 2009 and July
      2014 at our institute were reviewed and compared. Past medical history, the
      American Society of Anesthesiologists score, perioperative mortality,
      complication and revision surgeries rates were analyzed. Patient outcomes
      included: the visual analog scale and the EQ-5D scores. RESULTS: The mean age was
      68.58 +/- 11 years in the diabetic group and 51.7 +/- 17.7 years in the control
      group. No major postoperative complications were recorded in either group. Both
      groups were statistically equivalent in their postoperative length of stay, minor
      complications and revision rates. Both groups showed significant improvement in
      their outcome scores following surgery. CONCLUSIONS: Our results indicate that
      minimally invasive decompressive surgery is a safe and effective treatment for
      diabetic patients and does not pose an increased risk of complications. Future
      prospective studies are necessary to validate the specific advantages of the
      minimally invasive techniques in the diabetic population. These slides can be
      retrieved under Electronic Supplementary Material.

PMID- 30099671
TI  - Prediction of glandularity and breast radiation dose from mammography results in
      Japanese women.
AB  - Glandularity has a marked impact on the incidence of breast cancer and the missed
      lesion rate of mammography. The aim of this study was to develop a novel model
      for predicting glandularity and patient radiation dose using physical factors
      that are easily determined prior to mammography. Data regarding glandularity and
      mean glandular dose were obtained from 331 mammograms. A stepwise multiple
      regression analysis model was developed to predict glandularity using age,
      compressed breast thickness and body mass index (BMI), while a model to predict
      mean glandular dose was created using quantified glandularity, age, compressed
      breast thickness, height and body weight. The most significant factor for
      predicting glandularity was age, the influence of which was 1.8 times that of
      BMI. The most significant factor for predicting mean glandular dose was
      compressed breast thickness, the influence of which was 1.4 times that of
      glandularity, 3.5 times that of age and 6.1 times that of height. Both models
      were statistically significant (both p < 0.0001). Easily determined physical
      factors were able to explain 42.8% of the total variance in glandularity and
      62.4% of the variance in mean glandular dose. Graphical abstract Validation
      results of the above prediction model made using physical factors in Japanese
      women. The plotted points of actual vs. prediction glandularity shown in a are
      distributed in the vicinity of the diagonal line, and the residual plot for
      predicted glandularity shows an almost random distribution as shown in b. These
      distributions indicate the appropriateness of the prediction model.

PMID- 30099672
TI  - The roots of SGLT inhibition: Laurent-Guillaume de Koninck, Jean Servais Stas and
      Freiherr Josef von Mering.

PMID- 30099669
TI  - The Global Spine Care Initiative: public health and prevention interventions for
      common spine disorders in low- and middle-income communities.
AB  - PURPOSE: The purpose of this study was to develop recommendations for prevention
      interventions for spinal disorders that could be delivered globally, but
      especially in underserved areas and in low- and middle-income countries. METHODS:
      We extracted risk factors, associations, and comorbidities of common spinal
      disorders (e.g., back and neck pain, spinal trauma, infection, developmental
      disorders) from a scoping review of meta-analyses and systematic reviews of
      clinical trials, cohort studies, case control studies, and cross-sectional
      studies. Categories were informed by the Global Spine Care Initiative (GSCI)
      classification system using the biopsychosocial model. Risk factors were
      clustered and mapped visually. Potential prevention interventions for individuals
      and communities were identified. RESULTS: Forty-one risk factors, 51
      associations, and 39 comorbidities were extracted; some were associated with more
      than one disorder. Interventions were at primary, secondary, tertiary, and
      quaternary prevention levels. Public health-related actions included screening
      for osteopenia, avoiding exposure to certain substances associated with spinal
      disorders, insuring adequate dietary intake for vitamins and minerals, smoking
      cessation, weight management, injury prevention, adequate physical activity, and
      avoiding harmful clinical practices (e.g., over-medicalization). CONCLUSION:
      Prevention principles and health promotion strategies were identified that were
      incorporated in the GSCI care pathway. Interventions should encourage healthy
      behaviors of individuals and promote public health interventions that are most
      likely to optimize physical and psychosocial health targeting the unique
      characteristics of each community. Prevention interventions that are implemented
      in medically underserved areas should be based upon best evidence, resource
      availability, and selected through group decision-making processes by individuals
      and the community. These slides can be retrieved under Electronic Supplementary
      Material.

PMID- 30099673
TI  - Effects of long-term dietary administration of estrogen receptor-beta agonist
      diarylpropionitrile on ovariectomized female ICR (CD-1) mice.
AB  - Diarylpropionitrile (DPN) is an estrogen receptor-beta-specific agonist that has
      been linked to neuroprotection, preserving cognitive function with age, the
      suppression of anxiety-like behaviors, inhibition of cancer growth, and other
      positive properties. We hypothesized that DPN may have pro-longevity properties.
      DPN was administered via feed at a dose corresponding to approximately 3
      mg/kg/day to ovariectomized female mice beginning at 7 months of age. Mice were
      followed for the duration of their lifespans while monitoring body mass, aspects
      of behavior, learning, memory, and frailty. DPN-treated mice gained more body
      mass over the first 2 years of age (17 months of the study). A test of voluntary
      running behavior at 24 months of age behavior revealed no deficits in DPN-treated
      mice, which were as likely as control mice to engage in extended bouts of wheel
      running, and did so at higher average speeds. DPN administration had anxiolytic
      like effects when measured using an elevated plus maze at 9 months of age. A
      mouse frailty index was used to assess age-related changes. The correlation
      between age and frailty differed between control and DPN-treated mice. Overall,
      dietary DPN administration had some beneficial effects on the aging phenotype of
      ovariectomized female mice with few significant detrimental effects.

PMID- 30099674
TI  - Negative-pressure wound therapy for management of chronic neuropathic noninfected
      diabetic foot ulcerations - short-term efficacy and long-term outcomes.
AB  - PURPOSE: Negative pressure wound therapy (NPWT) is an adjunct method used in the
      treatment of diabetic foot ulceration (DFU). Real world data on its effectiveness
      and safety is scarce. In this prospective observational study, we assessed the
      short-term efficacy, safety, and long-term outcomes of NPWT in patients with type
      2 diabetes (T2DM) and neuropathic, noninfected DFUs. METHODS: Based on wound
      characteristics, mainly area (>1 vs. <=1 cm2), 75 patients with DFUs treated in
      an outpatient clinic were assigned to NPWT (n = 53) or standard therapy (n = 22).
      Wound area reduction was evaluated after 8 +/- 1 days. Long-term outcomes
      assessed included complete ulceration closure and recurrence rate. RESULTS:
      Patients assigned to NPWT were characterized by greater wound area (15.7 vs. 2.9
      cm2). Reduction in wound area was found in both the NPWT (-1.1 cm2, -10.2%, p =
      0.0001) and comparator group (-0.3 cm2, -18.0%, p = 0.0038). No serious adverse
      events related to NPWT were noted. Within 1 year, 55.1% (27/49) of DFUs were
      closed in the NPWT group and 73.7% (14/19) in the comparator group (p = 0.15). In
      the logistic regression, wound duration and smaller initial area, but not
      treatment mode, were associated with closure. One-year follow-up after DFU
      resolution revealed an ~30.0% recurrence rate in both groups (p = 0.88).
      CONCLUSIONS: NPWT is a safe treatment for neuropathic, nonischemic, and
      noninfected DFU in patients with T2DM, although this observational study did not
      prove its effectiveness over standard therapy. Additionally, we report a high
      rate of both closure and recurrence of ulcers, the latter irrespective of initial
      ulcer area.

PMID- 30099675
TI  - Galectin-3 deficiency enhances type 2 immune cell-mediated myocarditis in mice.
AB  - Experimental autoimmune myocarditis (EAM) is a mouse model of immune-mediated
      myocarditis and cardiomyopathy. The role of Galectin-3 (Gal-3), a beta
      galactoside-binding lectin, in autoimmune myocarditis has not been studied.
      Therefore, the aim of this study was to delineate the role of Gal-3 in myosin
      peptide-induced autoimmune myocarditis in mice. EAM was induced in relatively
      resistant C57BL/6J mice (wild type, WT) and in mice with a targeted deletion of
      Gal-3 gene (Gal-3KO) by immunization with myosin peptide MyHCalpha334-352. Gal
      3KO mice developed more severe myocarditis and more pronounced heart hypertrophy
      than WT mice. Increased infiltration of CD45+ leucocytes, CD3+ T cells, F4/80+
      macrophages, and eosinophils was observed in hearts of Gal-3KO mice compared to
      WT mice on day 21 after EAM induction. Moreover, hearts of Gal-3KO mice had more
      T helper type 2 (Th2) cells, alternatively activated M2 macrophages, higher
      amounts of IgG deposits, and higher serum levels of IL-4 and IL-33 than WT mice.
      Ablation of Gal-3 in Th1-dominant C57BL/6J mice that are relatively resistant to
      EAM resulted in more severe disease characterized by type 2 cardiac inflammation.
      The complex effects of Gal-3 on EAM progression might be important in the
      consideration of therapeutic options for the treatment of EAM.

PMID- 30099676
TI  - Rutin protects against lipopolysaccharide-induced mastitis by inhibiting the
      activation of the NF-kappaB signaling pathway and attenuating endoplasmic
      reticulum stress.
AB  - Rutin, found widely in traditional Chinese medicine materials, is used to treat
      eye swelling and pain, hypertension, and hyperlipidemia. In the present study, a
      mouse mastitis model induced by lipopolysaccharide (LPS) was established to
      explore rutin's inhibitory mechanism on mastitis via nuclear factor kappa B (NF
      kappaB) inflammatory signaling and the relationship between NF-kappaB signaling
      and endoplasmic reticulum (ER) stress. Mice were divided into six groups: Control
      group, LPS model group, LPS + rutin (25, 50, and 100 mg/kg) and LPS +
      dexamethasone (DEX) group. DEX, rutin, and PBS (control and LPS groups) were
      administered 1 h before and 12 h after perfusion of LPS. After LPS stimulation
      for 24 h, to evaluate rutin's therapeutic effect on mastitis, the mammary tissues
      of each group were collected to detect histopathological injury, tumor necrosis
      factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6 mRNA and protein
      levels; and glucose-regulated protein, 78 kDa (GRP78) protein levels. The protein
      and mRNA levels of TNF-alpha, IL-1beta, and IL-6 in the LPS + rutin group were
      significantly lower than those in the LPS model group. Similarly, p50/p105,
      phosphorylated (p)-p65/p65 and p-inhibitor of nuclear factor kappa b kinase
      subunit beta (p-IKKbeta)/IKKbeta ratios in the LPS + rutin group (50 mg/kg) and
      LPS + rutin group (100 mg/kg) decreased significantly. GRP78 protein expression
      was significantly higher in LPS + rutin group (100 mg/kg). The structure of
      mammary tissue became gradually more intact and vacuolization of acini decreased
      as the rutin concentration increased. The nuclear quantity of p65 in the LPS +
      rutin group decreased significantly in a rutin dose-dependent manner. Rutin had
      an anti-inflammatory effect in the LPS-induced mouse mastitis model, manifested
      by inhibition of NF-kappaB pathway activation and attenuation of ER stress.

PMID- 30099677
TI  - Genome-wide evidences of bisphenol a toxicity using Schizosaccharomyces pombe.
AB  - To clarify reliable toxic mechanisms of bisphenol A (BPA), an endocrine
      disrupting chemical, we approached an alternative animal and whole genome
      analyses with the yeast knockout library (YKO) of Schizosaccharomyces pombe. As
      results, the 50% growth inhibition concentrations (GI50) of BPA was approximately
      600 MUM and the YKO-three step screening revealed the top 10 target candidate
      genes including dbp2, utp18, srs1, tif224, use1, qcr1, etc. The screening results
      were confirmed in human embryonic stem cell (hES)-derived hepatic cells and HepG2
      human liver cancer cells. We found BPA down-regulated UQCRC, the human orthlog of
      S. pombe- qcr1, as a part of the mitochondrial respiratory chain, in HepG2 cells
      and hESs during cell differentiation into hepatic cells. Therefore, BPA may
      induce mitochondrial dysfunction and disruption of differentiation by suppressing
      UQCRC1.

PMID- 30099678
TI  - 3, 5, 3'-Triiodothyroacetic acid (TRIAC) is an anti-inflammatory drug that
      targets toll-like receptor 2.
AB  - Drug repositioning is a strategy that explores new pharmaceutical applications of
      previously launched or failed drugs, and is advantageous since it saves capital
      and time. In this study, we examined the inhibition of TLR2 signaling by drug
      candidates. HEK-BlueTM-hTLR2 cells were pretreated with drugs and stimulated
      using the TLR2 ligand, Pam3CSK4. Among the drugs that inhibited TLR2 signaling,
      we selected TRIAC, which is yet to be patented. Pretreatment with TRIAC decreased
      the TLR2 level and the phosphorylation of Akt and MAPKs in HEK-BlueTM-hTLR2
      cells. Since TLR2 is overexpressed in patients with acute hepatitis, we confirmed
      that TRIAC alleviates necrosis in a mouse model of Con A-induced acute hepatitis.
      The serum AST and ALT levels are indicators of liver damage, and are increased in
      Con A-induced hepatitis. Additionally, TLR2 and inflammatory cytokine levels are
      increased following administration of Con A and lead to liver damage. TRIAC
      decreased the serum levels of AST and ALT, and reduced liver tissue necrosis in
      mice with Con A-induced acute fulminant liver damage, by reducing the levels of
      inflammatory cytokines. In conclusion, TRIAC alleviates inflammation in mouse
      models of Con A-induced hepatitis by inhibiting the phosphorylation of Akt and
      MAPKs, the sub-mechanisms underlying TLR2 signaling.

PMID- 30099681
TI  - Long-Term Monokaryotic Cultures of Pleurotus ostreatus var. florida Produce High
      and Stable Laccase Activity Capable to Degrade beta-Carotene.
AB  - An extracellular laccase (Lacc10) was discovered in submerged cultures of
      Pleurotus ostreatus var. florida bleaching beta-carotene effectively without the
      addition of a mediator (650 mU/L, pH 4). Heterologous expression in P. pastoris
      confirmed the activity and structural analyses revealed a carotenoid-binding
      domain, which formed the substrate-binding pocket and is reported here for the
      first time. In order to increase activity, 106 basidiospore-derived monokaryons
      and crosses of compatible progenies were generated. These showed high
      intraspecific variability in growth rate and enzyme formation. Seventy-two
      homokaryons exhibited a higher activity-to-growth-rate-relation than the parental
      dikaryon, and one isolate produced a very high activity (1800 mU/L), while most
      of the dikaryotic hybrids showed lower activity. The analysis of the laccase gene
      of the monokaryons revealed two sequences differing in three amino acids, but the
      primary sequences gave no clue for the diversity of activity. The enzyme
      production in submerged cultures of monokaryons was stable over seven sub
      cultivation cycles.

PMID- 30099680
TI  - Dissimilatory arsenate-respiring prokaryotes catalyze the dissolution, reduction
      and release of arsenic from paddy soils into groundwater: implication for the
      effect of sulfate.
AB  - The paddy soils in some areas in Jianghan Plain were severely contaminated by
      arsenic. However, little is known about the activity and diversity of the
      dissimilatory arsenate-respiring prokaryotes (DARPs) in the paddy soils, and the
      effects of sulfate on the microbial mobilization and release of arsenic from
      soils into solution. To address this issue, we collected arsenic-rich soils from
      the depths of 1.6 and 4.6 m in a paddy region in the Xiantao city, Hubei
      Province, China. Microcosm assays indicated that all of the soils have
      significant arsenate-respiring activities using lactate, pyruvate or acetate as
      the sole electron donor. Functional gene cloning and analysis suggest that there
      are diverse DARPs in the indigenous microbial communities of the soils. They
      efficiently promoted the mobilization, reduction and release of arsenic and iron
      from soils under anaerobic conditions. Remarkably, when sulfate was amended into
      the microcosms, the microorganisms-catalyzed reduction and release of arsenic and
      iron were significantly increased. We further found that sulfate significantly
      enhanced the arsenate-respiring reductase gene abundances in the soils. Taken
      together, a diversity of DARPs in the paddy soils significantly catalyzed the
      dissolution, reduction and release of arsenic and iron from insoluble phase into
      solution, and the presence of sulfate significantly increased the microbial
      reactions.

PMID- 30099679
TI  - Sex Differences in Neuropathology and Cognitive Behavior in APP/PS1/tau Triple
      Transgenic Mouse Model of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is the most common form of dementia among the elderly,
      characterized by amyloid plaques, neurofibrillary tangles, and neuroinflammation
      in the brain, as well as impaired cognitive behaviors. A sex difference in the
      prevalence of AD has been noted, while sex differences in the cerebral pathology
      and relevant molecular mechanisms are not well clarified. In the present study,
      we systematically investigated the sex differences in pathological
      characteristics and cognitive behavior in 12-month-old male and female
      APP/PS1/tau triple-transgenic AD mice (3*Tg-AD mice) and examined the molecular
      mechanisms. We found that female 3*Tg-AD mice displayed more prominent amyloid
      plaques, neurofibrillary tangles, neuroinflammation, and spatial cognitive
      deficits than male 3*Tg-AD mice. Furthermore, the expression levels of
      hippocampal protein kinase A-cAMP response element-binding protein (PKA-CREB) and
      p38-mitogen-activated protein kinases (MAPK) also showed sex difference in the AD
      mice, with a significant increase in the levels of p-PKA/p-CREB and a decrease in
      the p-p38 in female, but not male, 3*Tg-AD mice. We suggest that an estrogen
      deficiency-induced PKA-CREB-MAPK signaling disorder in 12-month-old female 3*Tg
      AD mice might be involved in the serious pathological and cognitive damage in
      these mice. Therefore, sex differences should be taken into account in
      investigating AD biomarkers and related target molecules, and estrogen
      supplementation or PKA-CREB-MAPK stabilization could be beneficial in relieving
      the pathological damage in AD and improving the cognitive behavior of
      reproductively-senescent females.

PMID- 30099683
TI  - Development of an oxidative stress sensor in live bacteria using the optimized
      HyPer2 protein.
AB  - Oxidative stress is a key regulator in many cellular processes but also an
      important burden for living organisms. The source of oxidative damage usually is
      difficult to measure and assess with analytical tools or chemical indicators. One
      major limitation is to discriminate the presence of secondary oxidant molecules
      derived from the cellular metabolism after exposure to the oxidant or the
      scavenging capacity of reactive oxygen species by cells. Using a whole-cell
      reporter system based on an optimized HyPer2 protein for Escherichia coli
      expression, we demonstrate that, as previously shown for eukaryotic organisms,
      the effect at the transcriptional level of hydrogen peroxide can be monitored in
      vivo using flow cytometry of bacterial cells without the need of a direct
      analytical measurement. In this approach, we generated two different HyPer2
      expression systems, one that is induced by IPTG and a second one that is induced
      by oxidative stress responsive promoters to control the expression of the HyPer2
      protein and the exposure of higher H2O2 concentrations that has been shown to
      activate oxidative response genes. Both systems showed that the pathway that
      leads to the generation of H2O2 in vivo can be traced from H2O2 exposure. Our
      results indicate that hydrogen peroxide pulses can be readily detected in E. coli
      cells by a defined fluorescence signature that is H2O2 concentration-dependent.
      Our findings indicate that although less sensitive than purified protein or
      expressed in eukaryotic cells, HyPer2 is a good bacterial sensor for H2O2. As
      proof of concept, this system was used to trace the oxidative capacity of
      Toluidine Blue O showing that oxidative stress and redox imbalance is generated
      inside the cell. This system is expanding the repertoire of whole cell probes
      available for tracing cellular stress in bacteria.

PMID- 30099682
TI  - Causes, background, and characteristics of binocular diplopia in the elderly.
AB  - PURPOSE: We evaluated the background and characteristics of elderly patients with
      binocular diplopia including diseases caused by abnormalities in orbital pulleys.
      STUDY DESIGN: Retrospective. METHODS: The participants were 236 patients aged 60
      years or older who visited Kitasato University Hospital complaining of binocular
      diplopia. We classified strabismus by types and investigated the causes for each
      group. We diagnosed orbital pulley disorders using magnetic resonance imaging
      (MRI). Patients with orbital pulley disorders exhibited esotropia and/or vertical
      strabismus and did not present with cranial nerve palsy, systemic illness, or
      ocular injury. RESULTS: Classification of strabismus types was: exotropia
      (24.2%); esotropia (25.0%); vertical strabismus (30.1%), combined strabismus
      (20.8%). There were 50.9% cases of strabismus associated with vertical deviation.
      The causes of disease in each group were as follows: in the exotropia group,
      50.9% convergence insufficiency exotropia, 21.1% basic exotropia; in the
      esotropia group: 35.6% orbital pulley disorder 33.9% sixth cranial nerve palsy;
      in the vertical strabismus group: 32.4% forth cranial nerve palsy, 31.0% orbital
      pulley disorder; in the combined strabismus group: 28.6% orbital pulley disorder,
      28.6% forth cranial nerve palsy. CONCLUSIONS: About half of the elderly patients
      with binocular diplopia exhibited vertical deviation. In addition, binocular
      diplopia was often caused by orbital pulley disorders. It is the first
      epidemiological study focusing on orbital pulley disorders diagnosed on the basis
      of MRI.

PMID- 30099684
TI  - Dimethyl Sulfoxide-Induced Tonic-Clonic Seizure and Cardiac Arrest During
      Infusion of Autologous Peripheral Blood Stem Cells.
AB  - Various side effects associated with dimethyl sulfoxide (DMSO) which is used for
      cryopreservation of bone marrow or peripheral blood progenitor cells (PBPCs) have
      been reported. Among the central nervous system side effects the epileptic
      seizures, stroke, transient and temporary leucoencephalopathy, and global amnesia
      are well known. Herein we report a 52-year-old man who experienced tonic-clonic
      seizure within minutes after the initiation of DMSO cryopreserved autologous PBPC
      infusion. Unfortunately, he also developed cardiac arrest and required intubation
      for ventilation after the seizure. Pathophysiology of acute neurological and
      cardiac toxicity is unclear, but may also be idiosyncratic. Clinicians should be
      aware of the toxicity of cryoprotectant agents during PBSC infusion. Determining
      the risk factors associated with increased DMSO toxicity and taking preventive
      actions is utmost important.

PMID- 30099685
TI  - GLO1 gene polymorphisms and their association with retinitis pigmentosa: a case
      control study in a Sicilian population.
AB  - Glyoxalase 1 (GLO1) is a ubiquitous cellular enzyme involved in detoxification of
      methylglyoxal (MGO), a cytotoxic byproduct of glycolysis, whose excess can cause
      oxidative stress. In retinitis pigmentosa (RP), the prevalent cause of blindness
      just during working life in the industrialized countries, oxidative stress
      represents one of the possible mechanisms leading to death of cones following
      that of rods in the retina. To date, the causes of secondary death of cones
      remain unclear and among proposed mechanisms are: the deprivation of trophic
      factors normally produced by healthy rods, a compromised uptake of nutrients to
      cones due to irreversible destruction of RPE-cone outer segment, microglial
      activation and following release of pro-inflammatory cytokines and rod-derived
      toxins. In present paper, role of oxidative stress due to an excess of MGO was
      evaluated. In particular, we wanted to determine whether single nucleotide
      polymorphisms (SNPs) in GLO1 influence enzyme activity, contributing to cone
      death in advanced RP. 120 healthy controls and 80 RP patients from Sicilian
      population were genotyped for three GLO1 common SNPs, rs1130534 (c.372A>T,
      p.G124G), rs2736654 (c.A332C, p.E111A) and rs1049346 (c.-7C>T, 5'-UTR). While
      c.A332C polymorphism was not associated with RP, c.372A>T showed an allelic
      association (T372 allele frequency = 70% vs 60% in controls, p = 0.0071).
      Conversely, c.-7C>T showed both genotypic (chi2 = 68.0952; p = 1.634e-15) and
      allelic associations (chi2 = 51.7094; p = 6.435e-13): mutated allele frequency
      was higher in controls than in patients, suggesting its possible protective role.
      RP susceptibility may be associated with two of the analyzed GLO1 polymorphisms
      (rs1130534 and rs1049346).

PMID- 30099687
TI  - Design, synthesis, cytotoxicity and molecular modeling studies of some novel
      fluorinated pyrazole-based heterocycles as anticancer and apoptosis-inducing
      agents.
AB  - 3,5-Diamino-4-(3-trifluoromethylphenyldiazenyl)-1H-pyrazole was used as a
      starting scaffold for the synthesis of new pyrazole-based heterocycles to study
      their effects on the proliferation of three human cancer cell lines; human liver
      carcinoma cell line (HepG-2), colon cancer cell line (HCT-116) and human breast
      cancer cell line (MCF-7) using MTT assay. The synthesized compounds were
      characterized on the basis of IR, 1H NMR, 13C NMR, mass spectral data and
      elemental analysis results. Cytotoxicity assay results revealed that some of the
      compounds showed potent growth inhibition against all the cell lines tested, with
      IC50 values in the range of 0.64-7.73 MUg/mL. Breast cancer cells were used for
      further detailed studies to understand the mechanism of cell growth inhibition
      and apoptosis-inducing effect of the most active compounds. The results indicated
      that compounds 3a, 10b and 11a arrested MCF-7 cells at G2/M phase of the cell
      cycle and might induce apoptosis via caspase-3-dependent pathway. Molecular
      modeling and binding mode analysis of the most active compounds to caspase 3
      active site further provide a synergistic mechanism for their pro-apoptotic
      effects. In order to explore the structural requirements controlling the observed
      cytotoxic properties, 3D pharmacophore model was generated.

PMID- 30099688
TI  - Facile and highly diastereo and regioselective synthesis of novel
      octahydroacridine-isoxazole and octahydroacridine-1,2,3-triazole molecular
      hybrids from citronella essential oil.
AB  - A novel and highly efficient synthetic approach for the expedite construction of
      new octahydroacridine-isoxazole- and octahydroacridine-1,2,3-triazole-based
      molecular hybrids is first reported. Rapid access to the octahydroacridine core
      was achieved in a highly diastereoselective fashion via cationic Povarov reaction
      of N-propargyl anilines and citronella essential oil (Cymbopogon nardus). The
      subsequent 1,3-dipolar and Cu (I) catalyzed alkyne-azide cycloaddition reaction
      of the terminal alkyne fragment with the corresponding oxime or azide affords the
      desired 3,5-isoxazoles and 1,2,3-triazoles, respectively, as interesting
      molecular hybrid models for pharmacological studies.

PMID- 30099686
TI  - Vicenin-2: a potential radiosensitizer of non-small cell lung cancer cells.
AB  - Non-small cell lung cancer (NSCLC) is a major form of cancer and is resistant to
      chemo- and radio-therapy. Vicenin-2 (VCN-2) is a flavonoid obtained from Ocimum
      sanctum L. and it has been reported to have radioprotective and anti-cancer
      properties. This study was conducted to check for the radiosensitizing potential
      of VCN-2 in the NSCLC cell line, NCI-H23. NCI-H23 cells were exposed to VCN-2
      singularly, and to X-rays with and without prior VCN-2 treatment. Cytotoxicity
      assay, cell proliferation assay, caspase-3 activity assay, DNA fragmentation
      assay and Western blotting for Rad50, MMP-2 and p21 were performed to investigate
      the radiosensitizing properties of VCN-2. Fibroblast survival assay was performed
      using HEK293T cells to check for any adverse effects of VCN-2 on normal
      fibroblast cell line. VCN-2 singularly and in combination with radiation reduced
      the surviving cancer cells, increased caspase-3 activity, increased DNA
      fragmentation, increased the levels of Rad50 and lowered levels of MMP-2 and p21
      proteins while being non-toxic and radioprotective to the fibroblast cells. VCN-2
      showed a potent radiosensitizing property while also showing a chemotherapeutic
      property against NSCLC cell line NCI-H23.

PMID- 30099689
TI  - Pediatric Sleep Related Problems: The Tip of the Iceberg.

PMID- 30099690
TI  - Depression Among Caregivers of Children with Cystic Fibrosis: Causes and
      Solutions.

PMID- 30099691
TI  - Can Estimation of Presepsin Levels in Endotracheal Aspirate Predict Early Onset
      Pneumonia in Newborns?

PMID- 30099692
TI  - "I Was Trying to Do the Maths": Exploring the Impact of Risk Communication in
      Discrete Choice Experiments.
AB  - BACKGROUND: Risk is increasingly used as an attribute in discrete choice
      experiments (DCEs). However, risk and probabilities are complex concepts that can
      be open to misinterpretation, potentially undermining the robustness of DCEs as a
      valuation method. This study aimed to understand how respondents made benefit
      risk trade-offs in a DCE and if these were affected by the communication of the
      risk attributes. METHODS: Female members of the public were recruited via local
      advertisements to participate in think-aloud interviews when completing a DCE
      eliciting their preferences for a hypothetical breast screening programme
      described by three attributes: probability of detecting a cancer; risk of
      unnecessary follow-up; and cost of screening. Women were randomised to receive
      risk information as either (1) percentages or (2) percentages and icon arrays.
      Interviews were digitally recorded then transcribed to generate qualitative data
      for thematic analysis. RESULTS: Nineteen women completed the interviews (icon
      arrays n = 9; percentages n = 10). Analysis revealed four key themes where women
      made references to (1) the nature of the task; (2) their feelings; (3) their
      experiences, for instance making analogies to similar risks; and (4) economic
      phenomena such as opportunity costs and discounting. CONCLUSION: Most women
      completed the DCE in line with economic theory; however, violations were
      identified. Women appeared to visualise risk whether they received icon arrays or
      percentages only. Providing clear instructions and graphics to aid interpretation
      of risk and qualitative piloting to verify understanding is recommended. Further
      investigation is required to determine if the process of verbalising thoughts
      changes the behaviour of respondents.

PMID- 30099693
TI  - Folate and Its Impact on Cancer Risk.
AB  - PURPOSE OF REVIEW: Research has evaluated the potential impact of folate on
      cancer risk with conflicting findings. Studies have demonstrated increased risk,
      no effect, and decreased risk. This review summarizes findings of mixed results
      between folate intake, serum levels, gene polymorphisms, and cancer risk based on
      meta-analyses from the past five years. RECENT FINDING: Low or deficient folate
      status is associated with increased risk of many cancers. Folic acid
      supplementation and higher serum levels are associated with increased risk of
      prostate cancer. Gene polymorphisms may impact risk in certain ethnic groups.
      Folate has been studied extensively due to its role in methylation and nucleotide
      synthesis. Further prospective studies are needed to clarify optimal levels for
      nutrient remediation and risk reduction in those at risk, as well as elucidate
      the association between high intake, high serum levels, and prostate cancer risk.
      Future considerations for cancer risk may include gene interactions with
      nutrients and environmental factors.

PMID- 30099694
TI  - Trichotillomania and Trichophagia: Modern Diagnostic and Therapeutic Methods.
AB  - Trichotillomania is a chronic, mental disease of impulse control, characterized
      by repetitive, compulsive, and self-induced hair pulling. It can occur at any age
      but is observed more often in adolescents, with a strong predominance in females.
      Diagnosis of trichotillomania may be difficult, and its effective treatment
      challenging. The aim of this study is to critically review current literature
      regarding diagnostic procedures and treatment of trichotillomania, including
      psychotherapy, N-acetylcysteine, naltrexone, topiramate, atypical neuroleptics,
      and selective serotonin-reuptake inhibitors. The importance of cooperation
      between dermatologists and psychiatrists is emphasized to shorten the time to
      diagnose the disease and begin appropriate treatment. Finally, trichotillomania
      is also often connected with trichophagia, which may lead to formation of
      trichobezoars and cause a direct danger to the patient's health and even life due
      to the risk of intestinal obstruction and the need for surgical intervention.
      Based on thorough literature review, we conclude that diagnosis of
      trichotillomania can be challenging. Trichoscopy could help to distinguish
      trichotillomania from other types of hair loss. Most clinical trials using
      various treatment options have been conducted on small groups of patients, and
      the potential benefits determined using various scales. Therefore, it is
      difficult to compare the effectiveness of different treatment methods. There is
      also a lack of studies assessing treatment efficacy over longer periods of time.
      Thus, there is a need to perform better-designed studies in the near future to
      optimize current treatment modalities for trichotillomania.

PMID- 30099696
TI  - Clinical and Molecular Characterization of Surgically Treated Oropharynx Squamous
      Cell Carcinoma Samples.
AB  - A better understanding of the clinical and molecular features of oropharyngeal
      squamous cell carcinomas (OPSCC) may help in the development of strategies for a
      better patient management, improving survival rates. This retrospective study
      conducted a clinical and molecular characterization of surgically treated OPSCC
      samples. Paraffin-embedded samples from a series of cases were screened for high
      risk (HR) human papillomavirus (HPV) infection, methylation of a 5-gene panel,
      p53 expression, and TP53 mutation. The study was conducted at Barretos Cancer
      Hospital. Twenty-five surgically treated OPSCC with available tissue were
      included in the study. Samples were classified according to HPV status and
      molecular features and some of these characteristics were associated to clinical
      data. Twenty percent of the cases were HR-HPV positive and 62.5% presented TP53
      mutations. DAPK hypermethylation was associated with HPV status (p = 0.023),
      while methylated CCNA1 was inversely related to TP53 mutations in primary tumors
      (p = 0.042) and associated with a better disease-free survival (22.3% vs. 100.0%;
      p = 0.028) and overall survival (8.0% vs. 100.0%; p = 0.012). The results show
      differences regarding molecular and clinical characteristics in the oropharynx
      cases identified that should be validated in more cases to confirm whether these
      differences are able to classify patients according to outcome and help in a more
      thorough patient management.

PMID- 30099695
TI  - Correction to: Novel Mutations in RASGRP1 Are Associated with Immunodeficiency,
      Immune Dysregulation, and EBV-Induced Lymphoma.
AB  - The original version of this article unfortunately contained mistakes in Author's
      name, in Table 1 and in result section.

PMID- 30099697
TI  - Low-dose Gamma Knife radiosurgery plus whole-brain radiation therapy for patients
      with 5 or more brain metastases with or without meningeal dissemination.
AB  - PURPOSE/OBJECTIVE(S): Radiosurgery plus whole-brain radiotherapy (WBRT) has been
      reported to be useful for patients with <= 4 brain metastases (BM), but we
      hypothesized that similar treatment may be applicable to patients with >= 5 BM
      with or without meningeal dissemination. The purpose of this study was to
      evaluate the efficacy and toxicity of low-dose Gamma Knife (GK) followed by WBRT
      for patients with advanced BM. MATERIALS/METHODS: Major eligibility criteria for
      this phase II study were: (1) >= 5 BM with or without meningeal dissemination and
      (2) the largest tumor diameter <= 4 cm. During 2013-2016, 40 patients (13 men and
      27 women) entered the study. Nineteen had meningeal dissemination. The GK dose
      was 12 Gy at the periphery when the longest diameter was 3-4 cm and 14 Gy when it
      was < 3 cm. The WBRT dose to the isocenter was 30 Gy in 10 fractions, or 37.5 Gy
      in 15 fractions for two patients, with an expected survival of > 12 months. The
      median number of target BM was 17.5. RESULTS: After GK plus WBRT for 40 patients,
      31 did not develop further intracranial recurrence until death or last follow-up,
      whereas 9 developed recurrence. With a follow-up period up to 24 months, the
      overall survival rate was 36% at 12 months and median survival time was 8 months.
      The cumulative incidence of intracranial recurrence was 25% at 12 months.
      Toxicity was considered acceptable. CONCLUSION: Treatment with low-dose GK
      followed by WBRT for advanced-stage BM appeared to contribute to local control.

PMID- 30099698
TI  - Cultivation of Adipose-Derived Stromal Cells on Intact Amniotic Membrane-Based
      Scaffold for Skin Tissue Engineering.
AB  - Application of cell-based skin substitutes has recently evolved as a novel
      treatment for hard-to-heal wounds. Here, we focus on the development of a novel
      skin substitute by seeding human adipose-derived stromal cells (ASCs) on
      acellular human amniotic membrane (HAM). This construction is probably associated
      with higher rates of host cell infiltration and implanted cell engraftment. ASCs
      are achieved by separation of stromal cells from lipoaspirates using collagenase
      digestion and acellular HAM was obtained by separation of outer membrane of the
      chorion and removing its epithelial cells.

PMID- 30099699
TI  - Determining Competitive Potential of Bone Metastatic Cancer Cells in the Murine
      Hematopoietic Stem Cell Niche.
AB  - The ability of cancer cells to compete with hematopoietic stem cells (HSCs) to
      target the bone marrow microenvironment, or the HSC niche, during the
      dissemination process is critical for the development of bone metastasis. Here,
      we describe the methods for testing the relative potential of cancer cells to
      compete with HSCs for occupancy of the HSC niche by measuring the peripheral
      blood level of engrafted HSCs by flow cytometry in mice after bone marrow
      transplantation and tandem cancer cell inoculation. This method is useful for
      determining the molecular mechanisms for the roles of HSCs in the regulation of
      bone metastases.

PMID- 30099700
TI  - Toll-like receptor-4 deficiency alleviates chronic intermittent hypoxia-induced
      renal injury, inflammation, and fibrosis.
AB  - BACKGROUND: Obstructive sleep apnea (OSA)-associated chronic kidney disease is
      mainly caused by chronic intermittent hypoxia (CIH) triggered renal damage. This
      study aims to investigate the role of toll-like receptor-4 (TLR4) in underlying
      mechanism involved chronic intermittent hypoxia (CIH)-induced renal damage.
      METHODS: C57BL/6J mice with normal TLR4 (TLR4 WT) or deficient TLR4 (TLR4 KO)
      were divided into four groups and exposed to normal air (NA) and CIH: TLR4 WT +
      NA, TLR4 KO + NA, TLR4 WT + CIH, and TLR4 KO + CIH. CIH lasted for 8 h/day and 7
      days/week for 6 weeks. Renal injury and inflammation were evaluated by histology
      and ELISA. Renal tubular apoptosis, macrophages, and fibroblasts recruitment were
      determined by TUNEL assay, immunofluorescence, and western blot. RESULTS: In
      response to CIH, TLR4 deficiency alleviated renal histological injury, renal
      dysfunction, and fibrosis. TLR4 deficiency ameliorated renal dysfunction (serum
      BUN and creatinine) and tubular endothelial apoptosis determined by
      immunofluorescence staining of CD31 and TUNEL, and western blot of apoptotic
      protein (caspase-3, c-caspase-3, and Bax/Bcl-2 ratio). Furthermore, we also found
      TLR4 deficiency abrogated CIH-induced macrophages (CD68) and fibroblasts (alpha
      SMA) recruitment, further reducing expression of extra-cellular matrix protein
      (collagen I and collagen IV) and inflammatory cytokines release (IL-6, TNF-alpha,
      and MCP-1). Finally, we used immunohistochemistry to demonstrate that TLR4
      deficiency attenuated increased expression of MyD88 and NF-kB p65 after CIH
      treatment. CONCLUSIONS: Our data suggest that TLR4 plays a vital role in CIH
      induced renal injury, inflammation and fibrosis, and inhibition of TLR4 probably
      provides a therapeutic potential for CIH-induced kidney damage.

PMID- 30099701
TI  - Safe drugs in drug facilitated crimes and acute intoxications in Northern Italy.
AB  - Toxicological analyses are often performed in drug-facilitated sexual assaults
      (DFSA), when the victim shows or reports impaired consciousness and reduced
      ability. However, in other crimes or fatalities, especially in cases of
      concurrent natural disease or when another likely cause of death has been
      established, the involvement of drugs can be overlooked. The aim of this study is
      to report a series of cases of (i) victims of drug-facilitated crimes (DFC) other
      than DFSA and (ii) victims of acute intoxications, in which "licit" psychoactive
      drugs were found in blood samples, with the aim of understanding in which
      circumstances and to what extent prescription drugs have been used for non
      medical purposes in recent Italian casuistry. Circumstantial, autopsy, and
      toxicological data were collected through a retrospective analysis performed
      between 2013 and 2017 in the Forensic Toxicology Unit of the University of
      Bologna. Cases of "DFC other than DFSA" and "Acute Intoxication" in which
      "psychoactive drugs" or "prescription drugs" or "licit drugs" were found in the
      blood samples of the victims were included in the study. Nine cases of DFC other
      than DFSA, and 11 cases of acute intoxication, were identified. Different
      categories of "licit" psychoactive drugs (e.g. hypnotics, antipsychotics,
      antidepressants, anticonvulsants) had been used to facilitate diverse types of
      crime (homicide, robberies, elder abuse, fatal poisoning) or acute intoxication
      (suicide, attempted suicide, accidental death). The circumstances of these cases,
      as well as toxicological findings in blood samples and other relevant forensic
      elements, are reported, summarized and discussed in this paper. The non-medical
      use of pharmaceuticals has been identified by recent forensic literature and the
      present study as a significant and growing phenomenon, and its implication in
      fatalities should be taken into consideration and accurately investigated through
      appropriate toxicological analysis. Our study presents an overview of the
      circumstances of non-medical use of prescription drugs, usually considered "safe
      drugs", and their involvement in cases of DFC, suicides and accidental
      intoxication. In order to estimate the real incidence of these medications in DFC
      and acute intoxication, and thus collect more analytical and contextual data,
      further studies are needed, along with effective cooperation among police
      officers, clinicians, forensic pathologists, and toxicologists.

PMID- 30099702
TI  - Electrical weapons and excited delirium: shocks, stress, and serum serotonin.
AB  - It has been suggested that a CEW (conducted electrical weapon) exposure could
      elicit a stress response that could cause ExDS (excited delirium syndrome). There
      are some parallels between the signs of ExDS and serotonin syndrome (SS).
      Electroconvulsive therapy raises serotonin levels and therefore provides a
      plausible link between CEW applications and elevated serotonin levels. This study
      was designed to determine whether a CEW exposure elevates serum serotonin. A
      total of 31 police academy cadets were exposed to a very broad-spread 5-s CEW
      stimulus from a TASER brand X26 CEW. Blood was drawn before and after the
      exposure and at 24 h post exposure to measure serum serotonin levels. Lactic acid
      and cortisol levels were also compared. Median serum serotonin levels were 30 IQR
      (21,46), 36 IQR (22,50), and 32 IQR (21,45) ng/mL before exposure, after
      exposure, and 24 h after exposure (NS by pooled comparisons). The increase from
      baseline to post-test serotonin (? median = +6, ? mean = +2.7) ng/mL was not
      significant by a paired T-test (p = .29) but was significant by the Wilcoxon
      signed-rank test (p = .037). The increase to post-test log serotonin was not
      significant by a paired T-test (p = .13) but was significant by the Wilcoxon test
      (p = .049). All serotonin levels remained within the normal reference range of 0
      200 ng/mL. Post-hoc analysis demonstrated that the study was powered to detect a
      1/2 SD change, in log serotonin, with a 90% likelihood. With a very-broad
      electrode spread, CEW exposure did not significantly raise serum serotonin
      levels.

PMID- 30099703
TI  - An Uncertainty Visual Analytics Framework for fMRI Functional Connectivity.
AB  - Analysis and interpretation of functional magnetic resonance imaging (fMRI) has
      been used to characterise many neuronal diseases, such as schizophrenia, bipolar
      disorder and Alzheimer's disease. Functional connectivity networks (FCNs) are
      widely used because they greatly reduce the amount of data that needs to be
      interpreted and they provide a common network structure that can be directly
      compared. However, FCNs contain a range of data uncertainties stemming from
      inherent limitations, e.g. during acquisition, as well as the loss of voxel-level
      data, and the use of thresholding in data abstraction. Additionally, human
      uncertainties arise during interpretation due to the complexity in understanding
      the data. While existing FCN visual analytics tools have begun to mitigate the
      human ambiguities, reducing the impact of data limitations is an open problem. In
      this paper, we propose a novel visual analytics framework with three linked,
      purpose-designed components to evoke deeper interpretation of the fMRI data: (i)
      an enhanced FCN abstraction; (ii) a temporal signal viewer; and (iii) the
      anatomical context. Each component has been specifically designed with novel
      visual cues and interaction to expose the impact of uncertainties on the data. We
      augment this with two methods designed for comparing subjects, by using a small
      multiples and a marker approach. We demonstrate the enhancements enabled by our
      framework on three case studies of common research scenarios, using clinical
      schizophrenia data, which highlight the value in interpreting fMRI FCN data with
      an awareness of the uncertainties. Finally, we discuss our framework in the
      context of fMRI visual analytics and the extensibility of our approach.

PMID- 30099705
TI  - Profile of Dr. Shougong Zhang.

PMID- 30099704
TI  - Tracheal sounds accurately detect apnea in patients recovering from anesthesia.
AB  - Apnea should be monitored continuously in the post anesthesia care unit (PACU) to
      avoid serious complications. It has been confirmed that tracheal sounds can be
      used to detect apnea during sedation in healthy subjects, but the performance of
      this acoustic method has not been evaluated in patients with frequent apnea
      events in the PACU. Tracheal sounds were acquired from the patients in the PACU
      using a microphone encased in a plastic bell. Concurrently, a processed nasal
      pressure signal was used as a reference standard to identify real respiratory
      events. The logarithm of the tracheal sound variance (log-var) was used to detect
      apnea, and the results were compared to the reference method. Sensitivity,
      specificity, positive likelihood ratios (PLR), and negative likelihood ratios
      (NLR) were calculated. One hundred and twenty-one patients aged 55.5 +/- 13.2
      years (mean +/- SD) with a body mass index of 24.6 +/- 3.7 kg/m2 were included in
      data analysis. The total monitoring time was 52.6 h. Thirty-four patients
      experienced 236 events of apnea lasting for a total of 122.2 min. The log-var
      apnea detection algorithm detected apnea with 92% sensitivity, 98% specificity,
      46 PLR and 0.08 NLR. The performance of apnea detection in the PACU using the log
      var tracheal sounds method proved to be reliable and accurate. Tracheal sounds
      could be used to minimize the potential risks from apnea in PACU patients.

PMID- 30099706
TI  - Extraction and identification of the chyme proteins in the digestive tract of
      growing pigs.
AB  - This study aimed to explore the rule of degradation of dietary proteins by
      identifying chyme proteins in different segments of the digestive tract of
      growing pigs, using proteomics techniques. Six growing pigs were fed a corn
      soybean meal-based diet for 7 days. The feedstuff and chyme proteins were
      separately extracted and separated with SDS-PAGE. 2D LCMS/MS combined with
      protein database searching identified 1,513 proteins in different segments of the
      gastrointestinal tract, the number of identified exogenous proteins gradually
      decline from the stomach to colon, with large amounts in the duodenum to the
      large intestine. More corn proteins than soybean proteins were identified both in
      the feedstuff and chyme, and these were significantly decreased after digestion
      in the stomach. More membrane proteins than non-membrane proteins were identified
      in whole digestive tract. These results regarding the profiles of chyme proteins
      in different segments of the gastrointestinal tract would provide useful
      information for optimizing feed formula in pigs.

PMID- 30099707
TI  - Primate stem cells: bridge the translation from basic research to clinic
      application.
AB  - A growing body of literature has shown that stem cells are very effective for the
      treatment of degenerative diseases in rodents but these exciting results have not
      translated to clinical practice. The difference results from the divergence in
      genetic, metabolic, and physiological phenotypes between rodents and humans. The
      high degree of similarity between non-human primates (NHPs) and humans provides
      the most accurate models for preclinical studies of stem cell therapy. Using a
      NHP model to understand the following key issues, which cannot be addressed in
      humans or rodents, will be helpful for extending stem cell applications in the
      basic science and the clinic. These issues include pluripotency of primate stem
      cells, the safety and efficiency of stem cell therapy, and transplantation
      procedures of stem cells suitable for clinical translation. Here we review
      studies of the above issues in NHPs and current challenges of stem cell
      applications in both basic science and clinical therapies. We propose that the
      use of NHP models, in particular combining the serial production and
      transplantation procedures of stem cells is the most useful for preclinical
      studies designed to overcome these challenges.

PMID- 30099708
TI  - Chemical modulation of cell fates: in situ regeneration.
AB  - Chemical modulation of cell fates has been widely used to promote tissue and
      organ regeneration. Small molecules can target the self-renewal, expansion,
      differentiation, and survival of endogenous stem cells for enhancing their
      regenerative power or induce dedifferentiation or transdifferentiation of mature
      cells into proliferative progenitors or specialized cell types needed for
      regeneration. Here, we discuss current progress and potential using small
      molecules to promote in vivo regenerative processes by regulating the cell fate.
      Current studies of small molecules in regeneration will provide insights into
      developing safe and efficient chemical approaches for in situ tissue repair and
      regeneration.

PMID- 30099709
TI  - Resection of a plasma cell granuloma combining a conventional posterolateral left
      sided thoracotomy with a minimally invasive valve approach.
AB  - Plasma cell granuloma (PCG) is a rare benign tumor that is difficult to
      differentiate from malignancy. Depending on the location of the PCG, surgical
      management can be challenging. We describe a patient with a PCG involving the
      left lower lobe extending into the left atrium, that was resected en bloc using a
      conventional posterolateral thoracotomy combined with a surgical approach
      predominantly used for minimally invasive mitral valve surgery. This case
      illustrates how it is possible to utilize a technique used for cardiac surgery
      for tumors of pulmonary origin involving the heart.

PMID- 30099710
TI  - Mercury contamination in the sludge of drinking water treatment plants dumping
      into a reservoir in Rio de Janeiro, Brazil.
AB  - Although sludge piles from drinking water treatment plants can contain harmful
      substances, in many countries, their disposal methods are still unregulated.
      Besides aluminum, which is a major constituent in these residues, many other
      contaminants-like trace metals-can be present and may result from the quality of
      the raw materials used for water treatment. The application of these chemicals
      for the treatment of drinking water can generate toxic sludge and contaminate the
      produced water. In the present work, mercury contamination in the sludge piles of
      two drinking water treatment plants located along the margins of the Juturnaiba
      Reservoir, Southeast Brazil, was evaluated to verify whether contaminants are
      incorporated during water treatment. In the summer 2012, five cores were
      collected from the piles, and were analyzed for Eh, granulometry, total carbon,
      total nitrogen, and total mercury. The results indicated an anoxic environment,
      reflecting composition of the suspended matter. Carbon and nitrogen presented
      elevated concentrations, but also seemed to reproduce the characteristics of the
      suspended matter in the raw water. The concentrations of mercury were extremely
      variable but presented unexpectedly high values in some of the layers, reaching
      18,484 ng g-1. On the other hand, concentrations ten times lower than those
      observed in the natural system (8 ng g-1) could be observed. It was concluded
      that the only possible source for the contamination of the sludge was the
      chemicals used for water treatment.

PMID- 30099711
TI  - Environmental functions of biochar-a special issue for the 3rd Asia Pacific
      Biochar Conference (APBC 2016).

PMID- 30099712
TI  - Synergetic effect of hydrochar on the transport of anatase titanium dioxide
      nanoparticles in the presence of phosphate in saturated quartz sand.
AB  - The rapid development of nanomaterials has led to the unavoidable leakage and
      release of nanoparticles (NPs) into soil and the underlying groundwater. It is
      possible for chars and phosphate introduced into soil to improve crop soil
      properties by improving contact with NPs. In this study, the influences of
      hydrochar and/or phosphate on the anatase nTiO2 transport behaviors were
      investigated under different conditions. The breakthrough curves (BTCs) and
      retention profiles were obtained by the saturated sand column experiments. The
      additional analysis of zeta potentials, sedimentation kinetics, Raman mapping,
      and the two-site kinetic attachment model (TSKAM) was conducted to explore the
      possible underlying mechanisms. The simultaneous presence of phosphate and
      hydrochar acted in a synergetic fashion to enhance the transport of nTiO2 in a
      sand medium compared to the facilitated effect of single phosphate or hydrochar.
      The higher levels of hydrochar induce the more nTiO2 in the high IC solution
      passing through the saturated sand columns in the co-presence of phosphate. It
      was attributed to the competitive adsorption of hydrochar with nTiO2 to the sand
      site and the phosphate adsorption on nTiO2 occurred simultaneously through the
      sand columns. The fitting results of BTCs using TSKAM showed that the value of k2
      for nTiO2 (the irreversible attachment coefficient at site 2) was smaller than
      that of k1d/k1 (the first-order reversible detachment and attachment coefficient
      at site 1, respectively), suggesting irreversible retention of anatase nTiO2 at
      site 1. The value of k1d/k1 could be better used to explain the retention of
      nTiO2 with combined phosphate and hydrochar. This study provides insight into the
      implications of phosphate and/or hydrochar for nTiO2 transport in crop soil
      environments. Graphical abstract ?.

PMID- 30099714
TI  - Prediction of trastuzumab-induced cardiotoxicity in breast cancer patients
      receiving anthracycline-based chemotherapy.
AB  - BACKGROUND: Adjuvant trastuzumab improved overall survival and reduced the risk
      for disease recurrence in women with breast cancers, because of its potential
      cardiotoxicity, careful monitoring of left ventricular (LV) function during
      treatment is required. METHODS: This study investigates, whether myocardial
      strain imaging and level of N-terminal pro-brain natriuretic peptide (NT-pro BNP)
      could predict subsequent reduction in LVEF in breast cancer patients received
      adjuvant trastuzumab. 61 women with pathologically proven breast cancer HER-2
      positive received AC (Doxorubicin-Cyclophosphamide) for 4 cycles, followed by
      paclitaxel with Trastuzumab were enrolled. Clinical, conventional
      echocardiographic parameters, myocardial strain imaging [global longitudinal peak
      systolic strain (GLS), radial and circumferential systolic strain] and level of
      NT pro-BNP were measured at baseline, after 3, 6, 9 and 12 months of trastuzumab
      therapy. RESULTS: Of 61 patients, 18 patients (29.5%) developed trastuzumab
      induced cardiomyopathy (CM) at 6 and 9 months of therapy (LVEF declines >= 10%),
      GLS and radial strain significantly decreased in CM group at 3 months of
      trastuzumab treatment, the value of GLS at 3 months was the strongest predictors
      of cardiotoxicity its area under the curve (AUC 0.98) with an optimal cut-off for
      GLS (- 18%) having 92.5% sensitivity and 83% specificity. NT-pro BNP levels were
      not predictive of later trastuzumab-induced cardiac dysfunction. CONCLUSION:
      Myocardial strain imaging has been able to predict pre-clinical changes in LV
      systolic function and GLS is an independent early predictor of subsequent
      reduction in EF in breast cancer patients treated with trastuzumab.

PMID- 30099713
TI  - Uptake and accumulation of polycyclic aromatic hydrocarbons in the mangroves
      Avicennia marina and Rhizophora mucronata.
AB  - This study investigated the uptake and accumulation of polycyclic aromatic
      hydrocarbons (PAHs) in two mangrove species, Avicennia marina and Rhizophora
      mucronata. We tested the hypothesis that A. marina would absorb and accumulate
      more PAHs than R. mucronata. One-year old seedlings of both species were
      subjected to Bunker Fuel Oil 180 for 3 weeks, and the concentration of PAHs was
      analyzed by gas chromatography-mass spectrometry (GC/MS). The concentration of
      PAHs was significantly higher in A. marina than in R. mucronata. The major
      portion of the PAH pool was in roots (96% in A. marina, 98% in R. mucronata)
      compared to leaves. The dominant PAHs in roots of both species possessed two to
      three rings and included phenanthrene, anthracene, fluorene, and acenaphthene. In
      shoots, PAHs in A. marina included phenanthrene, chrysene, anthracene,
      acenaphthene, benzo[k+b]fluoranthene, pyrene, benzo[a] anthracene, and benzo[a]
      pyrene, while those in R. mucronata included phenanthrene, naphthalene,
      fluoranthene, fluorene, and acenaphthene. Phenanthrene was the dominant PAH in
      roots and shoots of both species. The greater susceptibility of A. marina appears
      to be due to its greater root length and specific root length, which permit more
      exposure to oil than R. mucronata. Other contributory factors include root
      anatomical characteristics such as larger air spaces, lower suberization of root
      epidermal cells, lower concentrations of polyphenols, tannins, lignin, and a less
      efficient antioxidative system. This study provides novel information on
      differences in the uptake and accumulation of PAHs in two contrasting mangrove
      species.

PMID- 30099715
TI  - Medical device patents-a review of contemporary global trends with an Irish
      comparison.
AB  - INTRODUCTION: Trends in medical technology patents provide an objective
      comparison of research and development between countries and over time. An
      analysis of these trends can benchmark innovation within Ireland in a worldwide
      context. By identifying and examining leading countries, domestic educational,
      infrastructural, regulatory and fiscal planning may be optimised. MATERIALS AND
      METHODS: Published data filing and granting reports from the two major patent
      offices (United States Patent and Trademark Office (USPTO) and European Patent
      Office (EPO)) were analysed. RESULTS: USPTO statistics demonstrated an 83.1%
      decrease in the overall number of medical device patents filed over the 10-year
      period, from 2005 (n = 1092) to 2015 (n = 185). Conversely, there was a 166%
      increase in the number of medical device patents granted over the same period.
      EPO applications in the field of medical technology represented the single
      largest industry category. The proportion of patents granted of Irish origin have
      increased from 0.7 (n = 22) to 0.9% (n = 73) over 10 years. Switzerland ranks
      first for medical device patents granted per head of population by the EPO, with
      Ireland ranking 5th. Ireland's medical device patents have increased dramatically
      per head of population, from 4.1 per million in 2012, to 15.3 in 2016. Israel has
      the highest number of USPTO patents granted per head of population, with Ireland
      ranking 5th. CONCLUSIONS: Ireland demonstrates high levels of medical technology
      patent filing per head of population, reflecting the importance of this industry.
      However, both Switzerland and Israel demonstrate dominance amongst smaller
      nations, and serving as benchmarks for national planning.

PMID- 30099716
TI  - Percutaneous dilatational tracheostomy versus fibre optic bronchoscopy-guided
      percutaneous dilatational tracheostomy in critically ill patients: a randomised
      controlled trial.
AB  - BACKGROUND: To determine whether fibre optic bronchoscopy-guided percutaneous
      dilatational tracheostomy (FOB-PDT) is a better option in critically ill
      patients, we compared the efficacy and incidence of procedure complications
      between PDT with and without FOB. METHODS: We included 90 patients with oral
      intubation and mechanical ventilation who received PDT with (n = 45, FOB-PDT
      group) and without (n = 45, PDT group) FOB. For all patients, a simplification of
      the Griggs technique was used in this study with a central venous catheter set
      and dilating forceps. Demographic data, body mass index (BMI), Sequential Organ
      Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation
      II (APACHE II) score, rate of first-time success, complication rate and time of
      procedure were evaluated in both groups. PDT was performed guided by FOB only in
      the FOB-PDT group. RESULTS: The rate of major complications, including minor or
      major haemorrhage requiring intervention and subcutaneous emphysema in the neck
      or pneumothorax, was significantly higher in the PDT group than in the PDT-FOB
      group (40% vs. 20%, P < 0.05). Significant differences were observed between the
      two groups with respect to the rate of first-time success (64.4% vs. 93.3%, P <
      0.05); the rate of first-time success puncture with the puncture needle in the
      PDT-FOB group was higher than that in the PDT group (93.3% vs. 75.6%, P < 0.05).
      The mean procedure duration was significantly longer in the PDT group than in the
      PDT-FOB group (12.9 +/- 1.1 vs. 9.8 +/- 1.2 min, P < 0 .05). CONCLUSIONS: PDT
      with FOB offers the advantages of a high rate of first-time success, a low
      complication rate and short-procedure duration. Thus, FOB-PDT is a better option
      in critically ill patients.

PMID- 30099717
TI  - High prevalence of risk factors for low bone mineral density and estimated
      fracture and fall risk among elderly medical inpatients: a missed opportunity.
AB  - AIMS: (1) To calculate the absolute fracture risk by using the fracture risk
      assessment (FRAX) model among elderly medical inpatients; (2) to assess the risk
      of falls, especially among patients with increased risk of fractures; and (3) to
      design and implement a bone health protocol to improve the assessment of fracture
      risk. METHODS: The study participants were all inpatients admitted to the medical
      wards at University Hospital Kerry, Ireland. All consecutive eligible patients
      aged >= 65 years were prospectively evaluated to populate clinical risk factor
      variables used in the FRAX model and the fall assessment was made by using
      Fracture Risk Questionnaire. RESULTS: Consecutive 465 medical inpatients were
      screened, and 200 eligible medical inpatients were evaluated. The mean age of the
      cohort was 73.8 +/- 9 years and 56% were male. The body mass index of the cohort
      was 27 +/- 5, and only 21% (n = 42) of patients reported having ever had a DXA
      scan. Previous personal history of low fragility fracture was present in 20.5% (n
      = 41) of the patients. The absolute 10-year risk of major osteoporotic and hip
      fracture was 15 +/- 12 and 7.6 +/- 11, respectively, and 25.5% (n = 51) and 64.5%
      (n = 129) respectively of the cohort had fracture risks exceeding the National
      Osteoporosis Federation (NOF) thresholds for treatment. High fall risk was noted
      in 63% of the cohort. CONCLUSIONS: A very high prevalence of fracture and fall
      risk was noted. A medical inpatient stay offers a window of opportunity for
      assessment of osteoporotic fracture risk. With these findings, a bone health
      protocol has been developed.

PMID- 30099718
TI  - Backbone and side chain NMR assignments for the ribosome Elongation Factor P (EF
      P) from Staphylococcus aureus.
AB  - Elongation Factor P (EF-P) is a 20.5 kDa protein that provides specialized
      translation of special stalling amino acid motifs. Proteins with stalling motifs
      are often involved in various processes, including stress resistance and
      virulence. Thus it has been shown that the virulent properties of microorganisms
      can be significantly reduced if the work of EF-P is disrupted. In order to
      elucidate the structure, dynamics and function of EF-P from Staphylococcus aureus
      (S. aureus), here we report backbone and side chains 1H, 13C and 15N chemical
      shift assignments of EF-P. Analysis of the backbone chemical shifts by TALOS+
      suggests that EF-P contains 1 alpha-helix and 13 beta-strands (beta1-beta2-beta3
      beta4-beta5-beta6-beta7-alpha1-beta8-beta9-beta10-beta11-beta12-beta13). The
      solution of the structure of this protein by NMR and X-ray diffraction analysis,
      as well as the structure of the ribosome complex by cryo-electron microscopy,
      will allow further screening of highly selective inhibitors of the translation of
      the pathogenic bacterium S. aureus. Here we report the almost complete 1H, 13C,
      15N backbone and side chain NMR assignment of a 20.5 kDa EF-P.

PMID- 30099719
TI  - Genetic associations between ADHD and dopaminergic genes (DAT1 and DRD4) VNTRs in
      Korean children.
AB  - It is well known that dopaminergic genes affect the development of attention
      deficit hyperactivity disorder (ADHD) in various populations. Many studies have
      shown that variable number tandem repeats (VNTRs) located within the 3'
      untranslated region of DAT1 and in exon 3 of DRD4 are associated with ADHD
      development; however, these results were inconsistent. Therefore, we investigated
      the genetic association between two VNTRs and ADHD in Korean children. We
      determined the VNTRs using PCR. We examined genotype and allele frequency
      differences between the experimental and control groups, along with the odds
      ratios, using Chi square and exact tests. We observed a significant association
      between the children with ADHD and the control group in the 10R/10R genotype of
      DAT1 VNTRs (p = 0.025). In addition, the 11R allele of DAT1 VNTRs showed a higher
      frequency in the control group than in the ADHD group (p = 0.023). Also, the
      short repeat (without 11R) and long repeat alleles (including 11R) were
      associated with ADHD (p < 0.05). The analysis of DRD4 VNTRs revealed that the 2R
      allele is associated with ADHD (p = 0.025). A significant result was also
      observed in long and short repeats (p < 0.05). Additionally, ADHD subtypes showed
      that the DRD4 VNTRs are associated with combined and hyperactive-impulsive
      subtype groups (p < 0.05). Therefore, our results suggest that DAT1 VNTRs and
      DRD4 VNTRs play a role in the genetic etiology of ADHD in Korean children.

PMID- 30099720
TI  - Genome-wide analyses of the Jeju, Thoroughbred, and Jeju crossbred horse
      populations using the high density SNP array.
AB  - The Jeju horse is an indigenous Korean horse breed that is currently registered
      with the Food and Agriculture Organization of the United Nations. However, there
      is severe lack of genomic studies on Jeju horse. This study was conducted to
      investigate genetic characteristics of horses including Jeju horse, Thoroughbred
      and Jeju crossbred (Jeju * Thoroughbred) populations. We compared the genomes of
      three horse populations using the Equine SNP70 Beadchip array. Short-range
      Linkage disequilibrium was the highest in Thoroughbred, whereas r2 values were
      lowest in Jeju horse. Expected heterozygosity was the highest in Jeju crossbred
      (0.351), followed by the Thoroughbred (0.337) and Jeju horse (0.311). The level
      of inbreeding was slightly higher in Thoroughbred (- 0.009) than in Jeju
      crossbred (- 0.035) and Jeju horse (- 0.038). FST value was the highest between
      Jeju horse and Thoroughbred (0.113), whereas Jeju crossbred and Thoroughbred
      showed the lowest value (0.031). The genetic relationship was further assessed by
      principal component analysis, suggesting that Jeju crossbred is more genetically
      similar to Thoroughbred than Jeju horse population. Additionally, we detected
      potential selection signatures, for example, in loci located on LCORL/NCAPG and
      PROP1 genes that are known to influence body. Genome-wide analyses of the three
      horse populations showed that all the breeds had somewhat a low level of
      inbreeding within each population. In the population structure analysis, we found
      that Jeju crossbred was genetically closer to Thoroughbred than Jeju horse.
      Furthermore, we identified several signatures of selection which might be
      associated with traits of interest. To our current knowledge, this study is the
      first genomic research, analyzing genetic relationships of Jeju horse,
      Thoroughbred and Jeju crossbred.

PMID- 30099721
TI  - A case of interdigitating dendritic cell sarcoma studied by whole-exome
      sequencing.
AB  - Interdigitating dendritic cell sarcoma (IDCS) is an aggressive neoplasm and is an
      extremely rare disease, with a challenging diagnosis. Etiology of IDCS is also
      unknown and most studies with only case reports. In our case,
      immunohistochemistry showed that the tumor cells were positive for S100, CD45,
      and CD68, but negative for CD1a and CD21. This study aimed to investigate the
      causative factors of IDCS by sequencing the protein-coding regions of IDCS. We
      performed whole-exome sequencing with genomic DNA from blood and sarcoma tissue
      of the IDCS patient using the Illumina Hiseq 2500 platform. After that, we
      conducted Sanger sequencing for validation of sarcoma-specific variants and gene
      ontology analysis using DAVID bioinformatics resources. Through comparing
      sequencing data of sarcoma with normal blood, we obtained 15 nonsynonymous single
      nucleotide polymorphisms (SNPs) as sarcoma-specific variants. Although the 15
      SNPs were not validated by Sanger sequencing due to tumor heterogeneity and low
      sensitivity of Sanger sequencing, we examined the function of the genes in which
      each SNP is located. Based on previous studies and gene ontology database, we
      found that POLQ encoding DNA polymerase theta enzyme and FNIP1 encoding tumor
      suppressor folliculin-interacting protein might have contributed to the IDCS. Our
      study provides potential causative genetic factors of IDCS and plays a role in
      advancing the understanding of IDCS pathogenesis.

PMID- 30099723
TI  - Effects of mandatory salt iodization on breast milk, urinary iodine
      concentrations, and thyroid hormones: is iodine deficiency still a continuing
      problem?
AB  - PURPOSE: To investigate whether mandatory use of iodized salt in Turkey, since
      1999 has sufficient effects on pregnant women and their newborns' urinary iodine
      concentrations (UIC), maternal and newborns' thyroid function tests and breast
      milk iodine concentrations (BMIC). METHODS: This cross-sectional analytical-type
      study was conducted in an obstetrics and gynecology hospital in Konya, Turkey.
      One hundred and seven pregnant women and their 107 full-term newborns were
      included into the study. Levels of pregnant women and their newborns' UIC,
      thyroid-stimulated hormone (TSH), free triiodothyronine (fT3), free thyroxine
      (fT4), thyroglobulin (Tg), and BMIC were studied. RESULTS: Of 107 women with term
      pregnancy, mean TSH value and hypothyroidism frequency were found as 2.34 +/-
      1.33 mIU/L and 18.7%, respectively. Cord blood TSH level was found higher (>= 10
      mIU/L) in five newborns. Accordingly, the incidence of transient congenital
      hypothyroidism was 4.7% (5/107). Tg levels were observed to be higher in 50.5% of
      newborns and 22.4% of pregnant women. Frequency of iodized salt use in
      pregnancies was detected as 96.3% in general population, 97.5% in urban, and
      92.9% in rural areas. Of pregnancies and newborns, 57.9 and 53.3% were found to
      have deficient urinary iodine, respectively, and BMIC deficiency was detected as
      52.0%. There was a significant positive correlation between pregnant women's UIC,
      and newborns' UIC and BMIC. CONCLUSIONS: Despite the effective struggle with
      iodine deficiency and salt iodination control program in Konya, we concluded that
      iodine deficiency still persists as a significant problem in pregnancies.

PMID- 30099722
TI  - CRISPR/Cas9-induced monoallelic mutations in the cytosolic AGPase large subunit
      gene APL2 induce the ectopic expression of APL2 and the corresponding small
      subunit gene APS2b in rice leaves.
AB  - The first committed step in the endosperm starch biosynthetic pathway is
      catalyzed by the cytosolic glucose-1-phosphate adenylyl transferase (AGPase)
      comprising large and small subunits encoded by the OsAPL2 and OsAPS2b genes,
      respectively. OsAPL2 is expressed solely in the endosperm so we hypothesized that
      mutating this gene would block starch biosynthesis in the endosperm without
      affecting the leaves. We used CRISPR/Cas9 to create two heterozygous mutants, one
      with a severely truncated and nonfunctional AGPase and the other with a C
      terminal structural modification causing a partial loss of activity.
      Unexpectedly, we observed starch depletion in the leaves of both mutants and a
      corresponding increase in the level of soluble sugars. This reflected the
      unanticipated expression of both OsAPL2 and OsAPS2b in the leaves, generating a
      complete ectopic AGPase in the leaf cytosol, and a corresponding decrease in the
      expression of the plastidial small subunit OsAPS2a that was only partially
      complemented by an increase in the expression of OsAPS1. The new cytosolic AGPase
      was not sufficient to compensate for the loss of plastidial AGPase, most likely
      because there is no wider starch biosynthesis pathway in the leaf cytosol and
      because pathway intermediates are not shuttled between the two compartments.

PMID- 30099724
TI  - Elevated extracellular trap formation and contact system activation in acute
      leukemia.
AB  - Leukemic cells release their nuclear contents into the extracellular space upon
      activation. The released nuclear contents, called extracellular traps, can
      activate the contact system of coagulation. This study accessed the extent of
      contact system activation, the levels of extracellular traps, and coagulation
      activation in hematologic malignancies including acute leukemia. In 154 patients
      with hematologic malignancies (acute leukemia, n = 29; myelodysplastic syndrome,
      n = 20; myeloproliferative neoplasms, n = 69; plasma cell myeloma, n = 36) and 48
      normal controls, the levels of coagulation factors (fibrinogen and factor VII,
      VIII, IX, and XII), D-dimer, thrombin generation, extracellular trap markers
      (histone-DNA complex, cell-free dsDNA, leukocyte elastase), and contact system
      markers (activated factor XII [XIIa], high-molecular-weight kininogen,
      prekallikrein, bradykinin) were measured. Patients with acute leukemia showed the
      highest levels of peak thrombin, extracellular trap markers, and factor XIIa.
      Factor XIIa level was significantly associated with the presence of acute
      leukemia. The histone-DNA complex and cell-free dsDNA were revealed as
      significant associated factors with the factor XIIa level. Three markers of
      extracellular traps and two markers of thrombin generation significantly
      contributed to the hemostatic abnormalities in hematologic malignancies. Contact
      system was activated in acute leukemia and its activation was significantly
      associated with the extent of extracellular trap formation. This finding suggests
      that extracellular traps might be a major source of contact system activation and
      therapeutic strategies targeting extracellular trap formation or contact system
      activation may be beneficial in acute leukemia.

PMID- 30099725
TI  - Molecular chaperone HSP70 prevents formation of inclusion bodies of the 25-kDa C
      terminal fragment of TDP-43 by preventing aggregate accumulation.
AB  - Transactive response DNA/RNA-binding protein 43-kDa (TDP-43) C-terminal
      fragments, such as a 25-kDa fragment (TDP-25), have been identified as a
      ubiquitinated and phosphorylated components of inclusion bodies (IBs) in motor
      neurons from amyotrophic lateral sclerosis patients. Cells contain proteins that
      function as molecular chaperones and prevent aggregate formation of misfolded and
      aggregation-prone proteins. Recently, we reported that heat shock protein
      (HSP)70, an abundant molecular chaperone, binds to TDP-25 in an ATP-dependent
      manner; however, whether HSP70 can prevent the formation of TDP-25-related IBs
      remains unknown. Here, we showed that HSP70 prevented TDP-25 aggregation
      according to green fluorescent protein-tagged TDP-25 (G-TDP-25) colocalization in
      the cytoplasm with mCherry-tagged HSP70 (HSP70-R). The mobile fraction of HSP70-R
      in the cytoplasmic IBs associated with G-TDP-25 increased relative to that of G
      TDP-25, suggesting that HSP70 strongly bound to G-TDP-25 in the IBs, whereas a
      portion remained dissociated from the IBs. Importantly, the proportion of G-TDP
      25 IBs was significantly decreased by HSP70-R overexpression; however, G-TDP-25
      levels in the insoluble fraction remained unchanged by HSP70-R overexpression,
      suggesting that G-TDP-25 formed aggregated species that cannot be dissolved, even
      in the presence of strong detergents. These results indicated that HSP70
      prevented the accumulation of G-TDP-25 aggregates in cytoplasmic IBs, but was
      insufficient for G-TDP-25 disassembly and solubilization.

PMID- 30099726
TI  - The effectiveness of a health promotion and stress-management intervention
      program in a sample of obese children and adolescents.
AB  - OBJECTIVE: Our study aimed to evaluate the effectiveness of an 8-week stress
      management intervention program that included progressive muscle relaxation,
      diaphragmatic breathing, guided imagery, and cognitive restructuring in obese
      Greek children and adolescents. DESIGN: Thirty-six patients were prospectively
      recruited to participate in this randomized controlled study. Of these, 16
      participants formed the intervention group and 20 participants the control group.
      Anthropometric measurements and salivary cortisol, determined serially 3 times a
      day, were assessed at the beginning and at the end of the study. Participants
      also completed the state-trait anxiety in children questionnaire (STAIC), the
      stress in children questionnaire (SiC), and the child behavior checklist (CBCL).
      RESULTS: The intervention resulted in a significant reduction of waist-hip ratio
      (p = 0.008) in the intervention group compared with the control group. Moreover,
      school performance was improved in the intervention group (p = 0.025), while both
      the intervention and the control group adopted healthier daily habits (p = 0.020
      and 0.011, respectively). However, there was no statistically significant
      difference between body mass index (BMI) z-score, stress, anxiety, and diurnal
      patterns in salivary cortisol. CONCLUSIONS: The present study supports the
      effectiveness of stress management intervention programs on waist-hip ratio
      reduction. Further research is required to investigate biomarkers able to predict
      and evaluate the effectiveness of stress management intervention programs.

PMID- 30099728
TI  - Cryogenic Numbing to Reduce Injection Discomfort during Indocyanine Green
      Lymphography.

PMID- 30099727
TI  - Australia's Progress in Improving Diets and Preventing Obesity: Clear
      Opportunities for Action.
AB  - PURPOSE OF REVIEW: Australia, like other developed countries, has a high
      prevalence of overweight and obesity, in both adults and children. This review
      examines progress in food policy in Australia, particularly at a national level,
      around key policy domains as well as in relation to public education. RECENT
      FINDINGS: Australia lacks a national nutrition strategy or an obesity prevention
      strategy, incorporating best practice recommendations to improve diets.
      Examination of current progress shows patchy implementation of key food policy
      initiatives and significant gaps, particularly at the federal level. In the
      absence of a long-term strategic approach, the response of the federal government
      has been ad hoc around the adoption of key policies and funding for programs to
      improve what Australians eat. Consensus around a platform for obesity prevention
      for national action, including food policy, is building from public health,
      academic and consumer groups.

PMID- 30099729
TI  - Outcome following Sternal Reconstruction with the Omental Flap.

PMID- 30099730
TI  - Hand Perfusion in Patients with Physiological or Pathological Allen's Tests.
AB  - INTRODUCTION:  The Allen test (AT) is a widely used clinical tool for the
      preoperative assessment of sufficient dual vessel hand perfusion although the
      impact of a pathological AT on tissue perfusion of the hand is not entirely
      clear. This study reveals perfusion changes of the hand in patients with
      pathological and physiological AT after terminating the dual blood supply.
      METHODS:  Patients were distributed into 2 groups (physiological and pathological
      AT) that each contained 25 members. Perfusion of the thumb, middle, and small
      fingers was measured with a laser Doppler based ("oxygen-to-see" [O2C]) device. A
      steady state was measured and also values at 1, 3, 5, and 10 minutes after radial
      occlusion were measured. RESULTS:  In patients with a physiological AT, only 1
      out of 18 values differed significantly from the steady state measurements after
      10 minutes, whereas patients with a pathological AT showed significant
      alterations in 8 out of 18 values. Oxygen saturation of the superficial and deep
      tissues appeared to be significantly worse in patients with a pathological AT.
      CONCLUSION:  Patients with a pathological AT suffered significantly more from the
      loss of dual hand perfusion than patients with a physiological AT. Patients with
      a pathological AT need more time to compensate for the altered perfusion pattern.

PMID- 30099731
TI  - Effect of Segment Length and Number of Osteotomy Sites on Cancellous Bone
      Perfusion in Free Fibula Flaps.
AB  - BACKGROUND:  Indocyanine green (ICG) videoangiography is routinely used to
      evaluate skin and organ perfusion and to assess patency rates of microvascular
      anastomoses. This study uses ICG angiography as a novel approach to qualitatively
      and quantitatively evaluate bone perfusion of microvascular fibula grafts
      intraoperatively and to assess the effect of fibula segment length and number of
      osteotomies on bone perfusion. METHODS:  All patients planned for mandible
      reconstruction using a microvascular fibula graft between January 2013 and May
      2017 were considered for this study. ICG videoangiography of cancellous bone
      perfusion was performed using a handheld ICG camera. Videos were analyzed, and a
      perfusion curve was generated. Peak enhancement, time to peak, slope, and wash-in
      area under the curve were extracted; rise time, wash-in rate (WiR), and wash-in
      perfusion index were calculated. Results were statistically analyzed with regard
      to distal fibula segment length and number of osteotomy sites. RESULTS:  Thirty
      nine patients (age 59 +/- 8 years) were included in the study. Mandible
      reconstruction was achieved with 1 (n = 15), 2 (n = 13), or 3 (n = 11) fibula
      segments. The WiR was 6.4 +/- 2.3 and 4.4 +/- 0.2 before and after proximal
      osteotomy, respectively. The wash-in perfusion index was 114.2 +/- 48.4 before
      and 84.4 +/- 20.0 after proximal osteotomy. Bone perfusion was significantly
      reduced after additional proximal osteotomies. Both the segment length and number
      of proximal osteotomies correlated with bone perfusion, with longer segments and
      fewer osteotomies showing higher perfusion. CONCLUSIONS:  This study demonstrates
      the feasibility of cancellous bone perfusion analysis using ICG and can serve as
      a basis for future bone perfusion studies. Additional osteotomies and short
      segment length negatively affects cancellous bone perfusion of the distal fibula
      segment in free fibula flaps. The extent to which the observed decrease in
      arterial inflow to the distal fibula segment affects the further course of
      healing needs to be addressed in future studies.

PMID- 30099732
TI  - A Hyperbaric Warm Perfusion System Preserves Tissue Composites Ex vivo and Delays
      the Onset of Acute Rejection.
AB  - BACKGROUND:  Ischemia-reperfusion injury (IRI) precipitates acute rejection of
      vascularized composite allografts (VCA). Hyperbaric preservation of tissues ex
      vivo, between harvest and revascularization, may reduce IRI and mitigate acute
      rejection of VCA. METHODS:  A porcine heterotopic musculocutaneous gracilis flap
      model was used. In phase 1, control autografts (n = 5) were infused with
      University of Wisconsin Solution (UWS) and stored at 4 degrees C for 3 hours.
      Intervention autografts (n = 5) were placed in a hyperbaric oxygen organ
      preservation system for 5 hours and infused with hyperoxygenated UWS at 20
      degrees C and 3 atm. Grafts were replanted into the animals' necks. In phase 2,
      similarly treated control (n = 8) and intervention grafts (n = 8) were
      allotransplanted into the necks of animals separated by a typed and standardized
      genetic mismatch. No systemic immunosuppression was given. Systemic markers of
      IRI, and clinical and histopathological assessments of necrosis and rejection
      were performed. RESULTS:  Autotransplanted tissue composites preserved in the
      hyperbaric chamber showed histopathological evidence of less muscle necrosis at 3
      hours (p = 0.05). Despite a longer period of ischemia, no evidence was found of a
      difference in systemic markers of IRI following revascularization in these
      groups. Allotransplanted tissues supported ex vivo within the hyperbaric
      perfusion device experienced acute rejection significantly later than
      corresponding controls. CONCLUSIONS:  Hyperbaric warm perfusion preserves
      musculocutaneous tissue composites ex vivo for longer than standard cold
      preservation in this model. This translates into a delay in acute rejection of
      allotransplanted tissue composites.

PMID- 30099733
TI  - Limb Salvage and Functional Outcomes following Free Tissue Transfer for the
      Treatment of Recalcitrant Diabetic Foot Ulcers.
AB  - BACKGROUND:  Recent evidence documenting high success rates following
      microvascular diabetic foot reconstruction has led to a paradigm shift in favor
      of more aggressive limb preservation. The primary aim of this study was to
      examine reconstructive and functional outcomes in patients who underwent free
      tissue transfer (FTT) for recalcitrant diabetic foot ulcers (DFUs) at our
      tertiary referral center for advanced limb salvage. METHODS:  Between June 2013
      and June 2016, 29 patients underwent lower extremity FTT for diabetic foot
      reconstruction by the senior author (K.K.E.). In all cases, microsurgical
      reconstruction was offered as an alternative to major amputation for the
      management of recalcitrant DFUs. Overall rates of flap survival, limb salvage,
      and postoperative ambulation were evaluated. The lower extremity functional scale
      (LEFS) score was used to assess functional outcomes after surgery. RESULTS: 
      Overall rates of flap success and lower limb salvage were 93 and 79%,
      respectively. Flap failure occurred in two patients with delayed microvascular
      compromise. Seven patients in this series ultimately required below-knee
      amputation secondary to recalcitrant infection (n = 5), intractable pain (n = 1),
      and limb ischemia (n = 1). The average interval between FTT and major amputation
      was 8 months (r, 0.2-15 months). Postoperative ambulation was confirmed in 25
      patients (86%) after a mean final follow-up of 25 months (r, 10-48 months). The
      average LEFS score for all patients was 46 out of 80 points (r, 12-80 points),
      indicating the ability to ambulate in the community with some limitations.
      CONCLUSIONS:  FTT for the management of recalcitrant DFUs is associated with high
      rates of reconstructive success and postoperative ambulation. However, several
      patients will eventually require major amputation for reasons unrelated to
      ultimate flap survival. These data should be used to counsel patients regarding
      the risks, functional implications, and prognosis of microvascular diabetic foot
      reconstruction.

PMID- 30099734
TI  - Exercise-Loaded Indocyanine Green Fluorescence Lymphangiography for Diagnosing
      Lymphedema.
AB  - BACKGROUND:  Indocyanine green (ICG) fluorescence lymphography (ICGLG) that can
      visualize the lymphatic vessel and its flow noninvasively and dynamically was
      developed in 2007. It is frequently used to observe the function and pathway of
      the lymphatic vessels. ICGLG is simple and easy to perform, and it is useful for
      understanding the condition of the lymphatic system in real time. However, its
      protocol is not standardized. In addition, the lymphatic flow is enhanced by an
      exercise load such as walking. Till now, there is no report of exercise-loaded
      ICGLG. Therefore, we aimed to shorten the examination time and establish a
      standard ICGLG protocol. METHODS:  We examined 63 patients (126 lower limbs) who
      visited our clinic for lower extremity edema. We observed detailed images of
      exercise-loaded ICGLG and examined the changes in findings over time in affected
      legs classified according to the International Society of Lymphedema. After ICG
      was injected, the participants exercised for 30 minutes. We observed the farthest
      proximal point where any ICG could be observed and the appearance of dermal
      backflow (DB), which is a specific finding of lymphedema, every 5 minutes.
      RESULTS:  The proximal migration speed of ICG tended to slow as the disease stage
      worsened. For all disease stages, after 20 minutes of exercise, the DB appearance
      rate did not change further. The rates were 0% for legs with stage 0 lymphedema,
      50% for legs with stage 1 lymphedema, and 100% for legs with stages 2a and 2b
      lymphedema. CONCLUSIONS:  The appropriate exercise duration after ICG injection
      is 20 minutes. ICGLG is useful for screening for lymphedema.

PMID- 30099735
TI  - Impact of Contralateral Symmetry Procedures on Long-Term Patient-Reported
      Outcomes following Unilateral Prosthetic Breast Reconstruction.
AB  - BACKGROUND:  One aim of unilateral postmastectomy breast reconstruction (BR) is
      to restore symmetry with the contralateral breast. As such, unilateral prosthetic
      reconstruction often requires a contralateral symmetry procedure (CSP). There is
      sparse literature on the impact of CSPs on long-term patient-reported outcomes
      (PROs) such as satisfaction and health-related quality of life (HRQoL). This
      study aims to describe PROs following CSPs, using a validated PRO tool, BREAST-Q.
      The hypothesis is that CSPs are associated with greater patient-reported
      satisfaction and HRQoL. METHODS:  This study is a single institutional analysis
      of prospectively collected BREAST-Q scores of patients who underwent unilateral
      prosthetic BR during 2011 to 2015. Women 18 years and older with BREAST-Q scores
      measured >= 9months after BR with or without CSP(s) at the time of expander
      replacement were included. Patients were classified into four subcohorts:
      augmentation, mastopexy, reduction, and no symmetry procedure (controls).
      Sociodemographic, clinical characteristics, and BREAST-Q scores were analyzed.
      Multivariable linear regression was performed. RESULTS:  Of 553 patients, 67
      (12%) underwent contralateral augmentation, 68 (12%) mastopexy, 93(17%)
      reduction, and 325 (59%) were controls. Mean follow-up time was 52 months.
      Satisfaction with breast and outcomes were higher in the augmentation compared
      with the control groups (p = 0.01). On multivariable analysis, augmentation
      remained an independent predictor of satisfaction with breast (p = 0.04).
      Physical well-being scores were lower for contralateral mastopexy and reduction
      compared with the controls with a trend toward statistical significance on
      multivariable models. Psychological and sexual well-being was similar across
      groups. CONCLUSION:  Prosthetic reconstruction with contralateral breast
      augmentation was associated with greater satisfaction with breast and
      reconstructive outcome. In contrast, breast reduction and mastopexy procedures
      demonstrated equivalent satisfaction with breasts compared with controls but may
      be associated with lower physical well-being. Such information can be used to
      improve the shared decision-making process for women who choose unilateral
      prosthetic BR.

PMID- 30099736
TI  - Volume Change of Pedicled Latissimus Dorsi Muscle Flap after Partial Breast
      Reconstruction.
AB  - INTRODUCTION:  Despite successful breast reconstruction with oversized latissimus
      dorsi muscle flap after breast-conserving surgery for breast cancer, esthetic
      problems continue to exist due to flap shrinkage. The purpose of this study was
      to evaluate the objective volume change of pedicled latissimus dorsi muscle flap
      when it is used in breast reconstruction. METHODS:  Patients who were diagnosed
      with breast cancer and underwent a breast-conserving surgery with immediate
      breast reconstruction with pedicled latissimus dorsi myocutaneous flap between
      October 2009 and November 2015 were studied. Eleven patients who were followed up
      for more than 1 year after operation were included in the study. We evaluated the
      volume of muscle portion of the latissimus dorsi myocutaneous flap with computed
      tomography (CT) scan. We analyzed the rate of volume change of the latissimus
      dorsi muscle every year until 5 years after the operation. RESULT:  The
      latissimus dorsi muscle flaps of all 11 patients showed a volume decrease over
      time. The rate of volume change of the latissimus dorsi muscle flaps decreased
      8.04% in the first year, 6.36% in the second year, 5.05% in the third year, 2.88%
      in the fourth year, and 2.56% in the fifth year after operation in average.
      CONCLUSION:  This research shows the possibility of objectively evaluating the
      volume change of pedicled latissimus dorsi muscle flaps after breast
      reconstruction. The findings will be helpful in designing the size of the flaps
      to use on defects after breast-conserving surgery.

PMID- 30099738
TI  - Sleep deprivation versus melatonin to induce sleep during paediatric
      electroencephalography.

PMID- 30099737
TI  - An ex vivo RNA trans-splicing strategy to correct human generalized severe
      epidermolysis bullosa simplex.
AB  - BACKGROUND: Generalized severe epidermolysis bullosa simplex (EBS-gen sev) is a
      genetic blistering skin disease in which autosomal dominant mutations in either
      the keratin KRT5 or KRT14 genes lead to impaired function of the intermediate
      filament cytoskeleton in the basal epidermis. Here we present an ex vivo RNA
      trans-splicing-based therapeutic approach to correct the phenotype. OBJECTIVES:
      To correct a mutation within exon 1 of the KRT14 gene, using a 5'-trans-splicing
      approach, where any mutation within the first seven exons could be replaced by a
      single therapeutic molecule. METHODS: A therapeutic RNA trans-splicing molecule
      containing wild-type exons 1-7 was stably transduced into an EBS patient-derived
      keratinocyte line. Trans-splicing was confirmed via reverse-transcriptase
      polymerase chain reaction, Western blotting and immunofluorescence microscopy.
      Skin equivalents generated from corrected keratinocytes were grafted onto nude
      mice and analysed about 8 weeks post-transplantation for regular epidermal
      stratification, trans-splicing-induced green fluorescent protein expression and
      blistering. RESULTS: Transplanted skin equivalents generated from trans-splicing
      corrected patient keratinocytes showed a stable and blister-free epidermis. KRT14
      correction disrupted EBS-gen sev-associated proinflammatory signalling, as shown
      at the mRNA and protein levels. Disruption of the pathogenic feedback loop in
      addition to overall downregulation of KRT14 expression highlighted the effect of
      KRT14 correction on the EBS pathomechanism. CONCLUSIONS: Our data demonstrate
      that trans-splicing-mediated mRNA therapy is an effective method for the
      correction of dominantly inherited KRT14 mutations at the transcriptional level.
      This results in the rescue of the EBS-gen sev phenotype and stabilization of the
      epidermis in a xenograft mouse model.

PMID- 30099739
TI  - Human CD8 T-cell activation in acute and chronic chikungunya infection.
AB  - There is a need for more detailed elucidation of T-cell immunity in chikungunya
      infection. CD8 T cells are one of main actors against viruses. Here, we analysed
      CD8+ T lymphocytes from patients in the acute and chronic phases of chikungunya
      disease (CHIKD). Our results demonstrate that CD8+ T cells expressed higher ex
      vivo granzyme B, perforin and CD107A expression in patients in the acute phase of
      CHIKD compared with healthy individuals and higher ex vivo expression of CD69,
      interleukin-17A, interleukin-10 and CD95 ligand, and co-expression of CD95/CD95
      ligand. These results elucidate the importance of these lymphocytes,
      demonstrating immune mechanisms mediated in human chikungunya infection.

PMID- 30099740
TI  - Effectiveness of technology-enhanced learning in Endodontic education: a
      systematic review and meta-analysis.
AB  - The aim of the present systematic review was to evaluate the effectiveness of
      technology-enhanced learning (TEL) in the field of Endodontics to improve
      educational outcomes compared to traditional learning methods. Randomized
      controlled studies published in English were identified from two electronic
      databases (PubMed and Scopus) up to May 2018. Two authors independently performed
      study selection, data extraction and assessed the risk of bias (ROB). Any
      teaching method using TEL was considered as the intervention, and this was
      compared to traditional methods. The outcome measuring the effectiveness of
      learning activities was evaluated by Kirkpatrick's four-level training evaluation
      model. The four levels of training outcomes are as follows: Reaction, Learning,
      Behaviour and Results. A meta-analysis was performed to estimate the standardized
      mean difference (SMD) by the random effects model. In total, 13 studies were
      included in the systematic review. Only three studies were assessed as 'low' ROB.
      A meta-analysis could not be performed in the domains of Reaction and Behaviour.
      No significant difference was observed in knowledge gain (Learning domain)
      between TEL and traditional methods (SMD, 0.14 (95% CI -0.10 to 0.39) I2  =
      62.7%). Similarly, no difference was observed in performance (Behaviour domain).
      A variable response was found in attitude (Reaction domain). From the available
      evidence, it can be concluded that TEL is equally as effective as traditional
      learning methods.

PMID- 30099741
TI  - Bacterial species associated with persistent apical periodontitis exert
      differential effects on osteogenic differentiation.
AB  - AIM: To determine if bacteria associated with persistent apical periodontitis
      induce species-specific pro-inflammatory cytokine responses in macrophages, and
      the effects of this species-specific microenvironment on osteogenic
      differentiation. METHODOLOGY: Macrophages were exposed to Enterococcus faecalis,
      Streptococcus oralis, Streptococcus mitis, Fusobacterium nucleatum, Treponema
      denticola or Tannerella forsythia, and levels of TNF-alpha and IL-1beta elicited
      were determined by immunoassay. Following treatment of MG-63 pre-osteoblasts with
      conditioned media from bacteria-exposed macrophages, osteogenic differentiation
      and viability of osteoblasts were analyzed by Alizarin Red Staining and MTS
      assay, respectively. Statistical analysis was carried out by one-way anova with
      the Tukey post-hoc test. Differences were considered to be significant if P <
      0.05. RESULTS: Macrophages exposed to Gram-positive bacteria did not produce
      significant amounts of cytokines. F. nucleatum-challenged macrophages produced up
      to four-fold more TNF-alpha and IL-1beta compared to T. denticola or T.
      forsythia. Only conditioned media from macrophages treated with Gram-negative
      bacteria decreased mineralization and viability of osteoblasts. CONCLUSIONS: Gram
      positive bacteria did not impact osteogenic differentiation and appeared
      innocuous. Gram-negative bacteria, in particular F. nucleatum elicited an
      enhanced pro-inflammatory response in macrophages, inhibited osteogenic
      differentiation and reduced cell viability. The findings suggest that the
      presence of this organism could potentially increase the severity of persistent
      apical periodontitis.

PMID- 30099742
TI  - Prevalence, risk factors, and mortality outcome in the drug reaction with
      eosinophilia and systemic symptoms patients with cardiac involvement.
AB  - BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS)
      syndrome is a severe cutaneous drug reaction that can affect multiple internal
      organ systems. Cardiac involvement in DRESS syndrome (CiDs) is uncommon but can
      be life-threatening. OBJECTIVE: To determine the prevalence, risk factors, and
      mortality outcome of CiDs. MATERIAL AND METHODS: Forty-one patients who were
      diagnosed with probable and definite DRESS syndrome according to the RegiSCAR
      criteria were recruited. Cardiac involvement was evaluated by two independent
      cardiologists. RESULTS: The cardiac involvement was found in 8/41 (19.5%)
      patients. Specifically, myocardial involvement was found in five patients, while
      three patients had pericardial involvement. The majority of culprit drugs were
      antibiotics followed by anti-epileptic medications. The hemoglobin and albumin
      levels were significantly lower in the patients with CiDs when compared to the
      patients without CiDs (P-value = 0.005 for both factors). The mortality rate at
      30 and 90 days was significantly higher among CiDs patients, that is, 3/8 (37.5%)
      versus 2/28 (6.1%); P-value = 0.02 and 4/8 (50.0%) versus 2/33 (6.1%); P-value =
      0.002 respectively. CONCLUSION: Our study showed the prevalence of CiDs was as
      high as 19.5% with high mortality rate. We suggest a thorough cardiac evaluation
      in all DRESS patients with RegiSCAR score >=4. The patients with CiDs had
      significantly lower hemoglobin and albumin levels, which might imply poor health
      condition, when compared to those without CiDs.

PMID- 30099743
TI  - HIV/AIDS Vaccines: 2018.
AB  - Human immunodeficiency virus (HIV) has infected 76 million people and killed an
      estimated 35 million. During its 40-year history, remarkable progress has been
      made on antiretroviral drugs. Progress toward a vaccine has also been made,
      although this has yet to deliver a licensed product. In 2007, I wrote a review,
      HIV AIDS Vaccines: 2007. This review, HIV AIDS Vaccines: 2018, focuses on the
      progress in the past 11 years. I begin with key challenges for the development of
      an AIDS vaccine and the lessons learned from the six completed efficacy trials,
      only one of which has met with some success.

PMID- 30099744
TI  - Normal and Injured Ankle Ligaments on Ultrasonography With Magnetic Resonance
      Imaging Correlation.
AB  - Ultrasonography (US) has been increasingly used in the evaluation of ankle
      ligamentous injuries given its advantages as a dynamic, efficient, noninvasive,
      and cost-effective imaging method. Understanding the anatomy of the ankle
      ligaments is critical for correct diagnosis and treatment. This pictorial essay
      describes and illustrates the US scanning technique and potential pitfalls in
      evaluating the ankle ligaments and also provides an overview of the US appearance
      of normal and injured ankle ligaments with magnetic resonance imaging
      correlation. Highlighted structures include the lateral complex, medial/deltoid
      complex, spring (calcaneonavicular) ligament complex, and syndesmosis.

PMID- 30099745
TI  - Ultrasonographic Characteristics of Pyriform Sinus Fistulas Involving the Thyroid
      Gland.
AB  - OBJECTIVES: Ultrasonography (US) has been considered to have a more limited role
      in the diagnosis of pyriform sinus fistulas than computed tomography. The aim of
      this study was to evaluate the US characteristics of pyriform sinus fistulas
      involving the thyroid gland in an attempt to improve our ability to diagnose this
      condition using US. METHODS: Between 2005 and 2016, 14 patients with pyriform
      sinus fistulas presenting as suppurative thyroiditis or as thyroid nodules were
      enrolled in the study. Their US images were reviewed to identify US
      characteristics indicating the presence of an underlying pyriform sinus fistula
      and compared with the computed tomographic images. RESULTS: A hypoechoic tubular
      lesion across the thyroid gland was identified in 9 patients (64.3%). Hyperechoic
      foci or echogenic lines were found within the lesion in 10 patients (71.4%). A
      hypoechoic rim was found at the boundary of the lesion in 7 patients (50.0%). A
      lesion emerging from the posterolateral aspect of the thyroid cartilage was found
      in 4 patients (28.6%). Thirteen (92.9%) of the 14 patients had 1 of these 4
      findings. CONCLUSIONS: Ultrasonography would be a useful diagnostic modality for
      indicating the presence of an underlying pyriform sinus fistula in patients with
      suppurative thyroiditis or a thyroid nodule and can be used as a first-line
      diagnostic tool to screen for pyriform sinus fistulas.

PMID- 30099746
TI  - In vitro evaluation of antagonism, modulation of cytokines and extracellular
      matrix proteins by Bifidobacterium strains.
AB  - : A healthy skin provides a protective barrier against pathogenic micro
      organisms. Recent studies have shown that probiotics, as those of Bifidobacterium
      genus, could act beneficially in dermatology, both when ingested and by topical
      use. In the present study, we evaluated by in vitro antagonism assays and using
      two skin cell lines the potential of four strains of Bifidobacterium spp. Among
      the four bifidobacteria, Bifidobacterium longum 51A was the only one able to
      inhibit the growth of the eight pathogenic indicators tested. Production of some
      cytokines and extracellular matrix proteins was determined when ccc or
      inactivated cells of the bifidobacteria were incubated with keratinocyte and/or
      fibroblast cell cultures. Significant results were observed only for IL-6, IL-8
      and IL-18 production, and inactivated Bifidobacterium pseudolongum 1191A was the
      only one which significantly stimulated collagen production, whereas lumican was
      stimulated by treatments with live Bifidobacterium bifidum 1622A , B. longum 51A
      and B. pseudolongum 1191A . Highest adhesion and internalization capabilities
      were observed with B. bifidum 1622A and Bifidobacterium breve 1101A . Concluding,
      B. longum 51A was highlighted for its antagonistic capacity and B. bifidum 1622A
      and B. pseudolongum 1191A for stimulating the production of cytokines and
      proteins of the extracellular matrix. SIGNIFICANCE AND IMPACT OF THE STUDY: The
      skin is the first line of defence against invasive micro-organisms, and its local
      microbiota provides additional protective functions based on antagonism against
      pathogenic micro-organisms and immunomodulation. Based on in vitro assays using
      Bifidobacterium spp. we demonstrated the antagonistic potential, as well as
      capacity in stimulating the production of cytokines and proteins of the
      extracellular matrix that these bacteria may exert on skin cells. This positive
      influence suggests the use of a consortium of these bifidobacteria in a topical
      product for dermatological treatments.

PMID- 30099747
TI  - Comorbidities and complications of polycystic ovary syndrome: An overview of
      systematic reviews.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common
      endocrinopathies affecting reproductive-aged women with adverse reproductive,
      metabolic and psychological outcomes. It has a complex pathophysiology and
      therefore requires a multidiscipline clinical approach. However, there remains
      limited research synthesizing the broad clinical implications of PCOS which would
      assist clinicians in the management of PCOS. OBJECTIVE: To summarize and appraise
      methodological quality of systematic reviews and meta-analyses evaluating
      complications and comorbidities associated with PCOS. METHODS: A literature
      search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed until 15
      September 2017. Article selection, data extraction and quality appraisal of
      included reviews using the Assessing the Methodological Quality of Systematic
      Reviews (AMSTAR) tool were performed in duplicate. A narrative synthesis of the
      findings was conducted. RESULTS: Twenty-three reviews were included. All reviews
      were of low (n = 2) to moderate quality (n = 21). PCOS was associated with
      adverse pregnancy outcomes (n = 2), impaired glucose tolerance (n = 6), insulin
      resistance (n = 6), increased risk of type 2 diabetes (n = 1), cardiovascular
      disease (n = 10), metabolic syndrome (n = 2), psychological stress (n = 7),
      endometrial cancer (n = 1) and vitamin D deficiency (n = 1). Obesity exacerbates
      many of these outcomes. CONCLUSIONS: There is a large body of reliable evidence
      for adverse metabolic outcomes and smaller, but consistent evidence for
      psychological issues in PCOS. We identified a shortage of systematic reviews
      regarding pregnancy outcomes of PCOS and significant gaps in knowledge of the
      association between PCOS and subclinical hyperthyroidism, vitamin D levels and
      cancers which future studies could aim to address.

PMID- 30099748
TI  - Methods for measurement of root canal curvature: a systematic and critical
      review.
AB  - The assessment of root canal curvature is essential for clinical and research
      purposes. This systematic review presents an overview of the published techniques
      for the measurement of root canal curvature features using imaging and to provide
      a critique of their clinical application. A database search in PubMed, PubMed
      Central, Embase, Scopus, EBSCO Dentistry & Oral Sciences Source and Virtual
      Health Library was conducted, using appropriate key words to identify measurement
      methods for root canal curvatures. The search strategy retrieved 10594 records in
      total, and 31 records fulfilled the inclusion criteria. From 2D image
      acquisitions, eleven studies measured exclusively the angle of curvature, an
      additional thirteen measured other curvature features (level, height, radius,
      length and shape). Seven reports described methods from 3D imaging (CBCT, MUCT).
      Root canal curvatures should be measured, for clinical proposes, to facilitate
      endodontic treatment planning, and in research, to reduce the risk of selection
      bias. This review has revealed that there are many methods described in the
      literature; however, no consensus exists on which method should be used. Some of
      the methodologies have potential clinical translation, whereas others are
      suitable for research purpose only, as they require a specific software or
      radiographic exposure in the mesiodistal direction.

PMID- 30099750
TI  - Pathogen infections and primary biliary cholangitis.
AB  - Primary biliary cholangitis (PBC) is a multi-factorial disease caused by the
      interaction of both genetic predisposition and environmental triggers. Bacterial
      infection has been investigated most intensively, both epidemiologically and
      experimentally, as a prime environmental aetiology in PBC. The association of
      recurrent history of urinary tract infection (UTI) with PBC has been frequently
      confirmed by several large-scale, case-control studies, despite variation in
      geographic area or case-finding methods. Escherichia coli is a predominant
      pathogen in most cases with UTI. Animal studies and molecular mimicry analysis
      between the human and E. coli E2 subunit of the 2-oxo-acid dehydrogenase
      complexes demonstrated that E. coli infection is a key factor in breaking
      immunological tolerance against the mitochondria, resulting in the production of
      anti-mitochondrial autoantibodies (AMA), the disease-specific autoantibodies of
      PBC. Novosphingobium aromaticivorans, a ubiquitous xenobiotic-metabolizing
      bacterium, is another candidate which may be involved in the aetiology of PBC.
      Meanwhile, improved environmental hygiene and increased prevalence of PBC,
      especially in males, may argue against the aetiological role of bacterial
      infection in PBC. Multiple mechanisms can result in the loss of tolerance to
      mitochondrial autoantigens in PBC; nonetheless, bacterial infection is probably
      one of the dominant pathways, especially in female patients. Notably, there is a
      rising prevalence of male patients with PBC. With increasing exposure to
      environmental xenobiotics in both genders, studies directed towards identifying
      the environmental culprit with systematically designed case-control studies are
      much needed to further determine the environmental factors and role of bacterial
      infections in PBC.

PMID- 30099749
TI  - Research update for articles published in EJCI in 2016.

PMID- 30099752
TI  - Evidence for changing nerve growth factor signalling mechanisms during
      development, maturation and ageing in the rat molar pulp.
AB  - AIM: To examine rat molar pulp innervation and identify complex cellular
      signalling systems involving nerve growth factor (NGF) and its p75 receptors
      (NGFR) at different stages of development, maturation and ageing. METHODOLOGY:
      Decalcified mandibular first molar mesial cusps from Wistar rats of ages 0 day;
      1, 2, 3, 4, 6, 9, 12 and 24 weeks (n = 5 per group) were sectioned (10 MUm) and
      incubated with antibodies for NGF, NGFR, calcitonin gene-related peptide (CGRP)
      and neurofilament. Nerve densities in worn and intact regions of 3- to 24-week
      old rats were compared by anova, Bonferroni and t-tests. RESULTS: During
      odontogenesis, differences in NGF and NGFR expression were observed, with no
      evidence of nerve fibres, suggesting a signalling mechanism controlling cellular
      differentiation and dentine formation. Tooth wear in 4-week rats was associated
      with reduced NGF expression and significantly decreased CGRP axons within
      affected odontoblast regions. The underlying subodontoblasts started expressing
      NGF which continued until 9 weeks. This may promote a significant increase in
      CGRP nerve density in affected regions. Nerve density in intact odontoblast
      regions increased gradually and reached significant levels in 12-week rats.
      Reduction in nerve densities within worn and intact regions of cusps was observed
      at 24 weeks. CONCLUSIONS: Age-related changes and responses to tooth wear may be
      controlled by the NGF signalling mechanism, with roles in
      odontoblast/subodontoblast communication and control of sensory innervation at
      different stages of tooth development, maturation and ageing. Greater
      understanding of cellular and nerve regulation in the injured pulp may promote
      therapeutic strategies for pulp survival.

PMID- 30099751
TI  - A cellular mechanism of muscle memory facilitates mitochondrial remodelling
      following resistance training.
AB  - KEY POINTS: Referring to the muscle memory theory, previously trained muscles
      acquire strength and volume much faster than naive muscles. Using extreme
      experimental models such as synergist ablation or steroid administration,
      previous studies have demonstrated that the number of nuclei increases when a
      muscle becomes enlarged, which serves as a cellular muscle memory mechanism for
      the muscle. In the present study, we found that, when rats were subjected to
      physiologically relevant resistance training, the number of myonuclei increased
      and was retained during a long-term detraining period. The acquired myonuclei
      were related to a greater degree of muscle hypertrophic and mitochondrial
      biogenesis processes following subsequent hypertrophic conditions. Our data
      suggest a cellular mechanism supporting the notion that exposing young muscles to
      resistance training would help to restore age-related muscle loss coupled with
      mitochondrial dysfunction in later life. ABSTRACT: Muscle hypertrophy induced by
      resistance training is accompanied by an increase in the number of myonuclei. The
      acquired myonuclei are viewed as a cellular component of muscle memory by which
      muscle enlargement is promoted during a re-training period. In the present study,
      we investigated the effect of exercise preconditioning on mitochondrial
      remodelling induced by resistance training. Sprague-Dawley rats were divided into
      four groups: untrained control, training, pre-training or re-training. The
      training groups were subjected to weight loaded-ladder climbing exercise
      training. Myonuclear numbers were significantly greater (up to 20%) in all
      trained muscles compared to untrained controls. Muscle mass was significantly
      higher in the re-training group compared to the training group (~2-fold
      increase). Mitochondrial content, mitochondrial biogenesis gene expression levels
      and mitochondrial DNA copy numbers were significantly higher in re-trained
      muscles compared to the others. Oxidative myofibres (type I) were significantly
      increased only in the re-trained muscles. Furthermore, in vitro studies using
      insulin-like growth factor-1-treated L6 rat myotubes demonstrated that myotubes
      with a higher myonuclear number confer greater expression levels of both
      mitochondrial and nuclear genes encoding for constitutive and regulatory
      mitochondrial proteins, which also showed a greater mitochondrial respiratory
      function. These data suggest that myonuclei acquired from previous training
      facilitate mitochondrial biogenesis in response to subsequent retraining by (at
      least in part) enhancing cross-talk between mitochondria and myonuclei in the pre
      conditioned myofibres.

PMID- 30099754
TI  - Shifts in Alcohol-Related Diagnoses After the Introduction of International
      Classification of Diseases, Tenth Revision, Clinical Modification Coding in U.S.
      Hospitals: Implications for Epidemiologic Research.
AB  - BACKGROUND: In October 2015, the United States transitioned healthcare diagnosis
      codes from the International Classification of Diseases, Ninth Revision, Clinical
      Modification (ICD-9-CM), to the Tenth Revision (ICD-10-CM). Trend analyses of
      alcohol-related stays could show discontinuities solely from the change in
      classification systems. This study examined the impact of the ICD-10-CM coding
      system on estimates of hospital stays involving alcohol-related diagnoses.
      METHODS: This analysis used 2014 to 2017 administrative data from the Agency for
      Healthcare Research and Quality Healthcare Cost and Utilization Project State
      Inpatient Databases for 17 states. Quarterly ICD-9-CM data from second quarter
      2014 through third quarter 2015 were concatenated with ICD-10-CM data from fourth
      quarter 2015 through first quarter 2017. Quarterly counts of alcohol-related
      stays were examined overall and then by 6 diagnostic subgroups: withdrawal,
      abuse, dependence, alcohol-induced mental disorders (AIMD), nonpsychiatric
      alcohol-induced disease, and intoxication or toxic effects. Within each group, we
      calculated the difference in the average number of stays between ICD-9-CM and ICD
      10-CM coding periods. RESULTS: On average, the number of stays involving any
      alcohol-related diagnosis in the 6 quarters before and after the ICD-10-CM
      transition was stable. However, substantial shifts in stays occurred for alcohol
      abuse, AIMD, and intoxication or toxic effects. For example, the average
      quarterly number of stays involving AIMD was 170.7% higher in the ICD-10-CM
      period than in the ICD-9-CM period. This increase was driven in large part by 1
      ICD-10-CM code, Alcohol use, unspecified with unspecified alcohol-induced
      disorder. CONCLUSIONS: Researchers conducting trend analyses of inpatient stays
      involving alcohol-related diagnoses should consider how ongoing modifications in
      the ICD-10-CM code system and coding guidelines might affect their work. An
      advisable approach for trend analyses across the ICD-10-CM transition is to
      aggregate diagnosis codes into broader, clinically meaningful groups-including a
      single global group that encompasses all alcohol-related stays-and then to select
      diagnostic groupings that minimize discontinuities between the 2 coding systems
      while providing useful information on this important indicator of population
      health.

PMID- 30099755
TI  - Utility of the 3-Vessel and 3-Vessel and Trachea Views in Prenatal Diagnosis of a
      Pulmonary Artery Sling.
AB  - A pulmonary artery (PA) sling is a very rare congenital cardiovascular anomaly,
      and only a few studies have reported PA slings in fetuses. The relationship of
      the PA, aorta, ductus arteriosus, and trachea can be evaluated in the 3-vessel
      and 3-vessel and trachea views during fetal echocardiography. A PA sling can be
      detected by abnormal positioning of the left PA in relation to the trachea when
      sweeping from the 3-vessel view cranially to the 3-vessel and trachea view. Here
      we report 3 cases of fetal PA slings and their follow-ups. Two cases were
      confirmed by postnatal echocardiography, and the other case was confirmed by a
      cardiovascular cast after pregnancy termination. We emphasize that the 3-vessel
      and 3-vessel and trachea views are of crucial importance in the prenatal
      diagnosis of a PA sling.

PMID- 30099753
TI  - Immunogenicity of meningococcal polysaccharide ACWY vaccine in primary immunized
      or revaccinated adults.
AB  - Meningococcal polysaccharide (Men-Ps) vaccine immunogenicity following either
      primary immunization or revaccination in adults was evaluated. The study
      population consisted of subjects who have received tetravalent Men-Ps vaccine
      once (group 1) or at least twice, with a 2-6 dose range (group 2). Human
      leucocyte antigen (HLA)-typing was performed by polymerase chain reaction and
      specific immunoglobulin (Ig)G was measured by enzyme-linked immunosorbent assay.
      Nine months post-immunization, the percentages of individuals with levels of anti
      Men-Ps IgG >= 2 ug/ml were comparable in both groups, with the exception of anti
      Men-PsW135 IgG, which were significantly higher in group 2. The percentage of
      subjects doubling IgG levels at 9 months was significantly higher in group 1. The
      high baseline anti-Men-Ps antibody levels negatively influenced the response to
      revaccination, suggesting a feedback control of specific IgG. The calculated
      durability of anti-Men-Ps IgG was 2.5-4.5 years, depending on the Men-Ps,
      following a single vaccine dose. No interference by other vaccinations nor HLA
      alleles association with immune response were observed. This study confirms that
      Men-Ps vaccine in adults is immunogenic, even when administered repeatedly, and
      underlines the vaccine suitability for large-scale adult immunization programmes
      that the higher costs of conjugate vaccines may limit in developing countries.

PMID- 30099756
TI  - Comparison of Ultrasound-Guided and Landmark-Based Lumbar Punctures in
      Inexperienced Resident Physicians.
AB  - OBJECTIVES: We sought to determine whether US-guided lumbar puncture reduced the
      rate of lumbar puncture failures for providers at an academic teaching hospital
      with variable lumbar puncture and US experience compared to the traditional
      landmark-based technique. METHODS: We conducted a prospective randomized
      controlled trial to compare US-guided lumbar puncture to the traditional landmark
      technique in an academic emergency department. Thirty-five patients were
      randomized to either have their lumbar puncture performed either via the landmark
      or US-guided technique. All procedures were completed by an emergency medicine
      resident with variable lumbar puncture and US experience. Procedural failures,
      the number of attempts, the time to completion, and patient pain scores were all
      recorded. RESULTS: The adjusted odds ratio of successfully obtaining
      cerebrospinal fluid (CSF) in the US-guided lumbar puncture group was 2.31
      compared to the landmark-based lumbar puncture group (P = .377). It took 1.54
      times more attempts to obtain CSF in the landmark group as it did in the US group
      (P = .046). It seemed to have no effect on postprocedural pain or the time to
      obtain CSF. CONCLUSIONS: The use of US guidance to assist in lumbar punctures did
      not improve the procedural success rate over traditional landmark techniques in
      an academic setting with novice providers. Although using US for procedural
      guidance significantly decreased the number of attempts, it seemed to have no
      effect on postprocedural pain or the time to obtain CSF.

PMID- 30099757
TI  - Minimally Invasive Treatment of Cesarean Scar and Cervical Pregnancies Using a
      Cervical Ripening Double Balloon Catheter: Expanding the Clinical Series.
AB  - The efficacy of treating cesarean scar pregnancies and cervical pregnancies with
      the Cook(r) cervical ripening balloon catheter, in a multicenter office-based
      setting is reported. Thirty-eight women were treated. Insertion of the catheter
      was performed under real-time ultrasound guidance. Patients received adjuvant
      systemic methotrexate, prophylactic oral antibiotics, and oral pain medication.
      Serum human chorionic gonadotropin and ultrasound scans were followed serially
      until resolution. Thirty-seven patients were successfully treated, requiring no
      further procedures. We found that the Cook cervical ripening balloon technique is
      a simple, effective, outpatient, minimally invasive treatment with few
      complications noted in this expanded series.

PMID- 30099758
TI  - Current Experience of Ultrasound Training in Otolaryngology Residency Programs.
AB  - OBJECTIVES: The applications of using ultrasound for the evaluation and
      management of otolaryngologic diagnoses are expanding. The purpose of this study
      was to evaluate the current experience of ultrasound training in otolaryngology
      residency programs. METHODS: All allopathic and osteopathic otolaryngology
      residency programs in the United States were surveyed online via an e-mailed
      survey link to the resident representatives of the Section for Residents and
      Fellows in Training of the American Academy of Otolaryngology-Head and Neck
      Surgery. We present a descriptive analysis of the survey results. RESULTS: A
      total of 110 responses were obtained from resident representatives at MD and DO
      otolaryngology residency programs, representing a response rate of 94.8%. Forty
      four percent of residents reported that they would not feel comfortable with
      performing ultrasound-guided procedures after residency; 43% reported that they
      do not perform ultrasound procedures as a part of their residency training; and
      60% of those trainees performing ultrasound procedures do not log the procedures.
      Twenty-three percent of residents did not have access to an ultrasound machine.
      Most respondents (71%) desired more exposure to diagnostic and/or interventional
      ultrasound training during residency. CONCLUSIONS: Although current experience is
      variable, there is a strong interest in increasing resident skill acquisition in
      ultrasound training among otolaryngology residents. Some barriers to these goals
      may be a lack of trained faculty members using ultrasound and insufficient
      recording mechanisms for residents performing ultrasound procedures.

PMID- 30099759
TI  - Mummified Thyroid Nodules: Conventional and Contrast-Enhanced Ultrasound
      Features.
AB  - OBJECTIVES: The purpose of our study was to highlight the conventional and
      contrast-enhanced ultrasound (US) features of mummified thyroid nodules, which
      should help differentiate them from histologically proven papillary thyroid
      carcinomas (PTCs). METHODS: Thirty-one patients with 33 mummified thyroid
      nodules, which showed suspicious US findings that were suggestive of malignancy,
      as well as 33 patients with 38 surgically confirmed PTCs were enrolled in this
      study. We evaluated the size, shape, margin, echogenicity, presence of shadowing
      and halo, presence of punctate echogenic foci, vascularity, and contrast
      enhancement parameters for each nodule. The final diagnosis of mummified thyroid
      nodules was confirmed via fine-needle aspiration (FNA) or surgery. RESULTS: Of
      the 33 mummified thyroid nodules, 9 (27.3%) were confirmed by surgery to be
      benign, and 24 (72.7%) were proven by FNA to be benign. A univariate analysis
      indicated that the mummified thyroid nodules more frequently showed wider-than
      tall shapes, marked hypoechogenicity, the presence of posterior shadowing, the
      absence of nodular vascularity, hypoenhancement or no enhancement, and peak index
      and area under the curve indices of less than 1 in the findings of preoperative
      US and contrast-enhanced US compared to PTCs. A multivariate analysis showed that
      marked hypoechogenicity and an area under the curve index of less than 1 were
      independent characteristics related to mummified nodules for discriminating from
      PTCs (all P < .05). CONCLUSIONS: Benign thyroid nodules may display shrinkage
      over time and may reveal malignant US features. Awareness of these findings and
      their connection with initial and follow-up US examinations should help identify
      mummified thyroid nodules and to avoid surgical excision or unnecessary FNA.

PMID- 30099760
TI  - Glucose and lipid metabolism, bone density, and body composition in individuals
      with Williams syndrome.
AB  - OBJECTIVE: We assessed body composition, bone mineral density (BMD), glucose and
      lipids in Williams syndrome (WS), a rare microdeletion disorder. DESIGN:
      Individuals with WS had outpatient assessment at Massachusetts General Hospital.
      Controls were selected from the National Health and Nutrition Examination Survey
      (NHANES 2005-2006). PATIENTS: A total of 22 individuals with WS, each matched by
      age, sex and race to four NHANES controls. MEASUREMENTS: Blood sampling, oral
      glucose tolerance test, dual-energy X-ray absorptiometry scan. RESULTS: WS and
      control groups were 59% female and 29 +/- 8 years old. Compared to controls,
      individuals with WS were shorter but had similar body weight, with more fat and
      less lean mass. Per cent body fat was higher in WS even after adjusting for BMI
      (+2.1% [95% CI 0.4, 3.9%]). Four WS patients had abnormal lower extremity fat
      accumulation resembling lipedema. HbA1c (+0.5% [0.2, 0.7]) and 2-hour glucose
      (+68 mg/dL [44, 93]) were higher in WS vs controls, differences which persisted
      after adjusting for BMI. Fasting glucose was comparable between groups. LDL (-18
      mg/dL [-35, -2]) and triglycerides (-45 mg/dL [-87, -2]) were significantly lower
      in WS. Whole-body BMD was significantly lower (-0.15 g/cm2 [-0.20, -0.11]) in WS,
      and this remained true controlling for height (-0.06 g/cm2 [-0.11, -0.02]).
      Vitamin D was <30 ng/mL in 81% of those with WS. CONCLUSIONS: On average, adults
      with WS have increased fat, decreased lean mass, impaired glucose homeostasis and
      reduced BMD. Clinical efforts to build muscle and bone mass, and to ensure
      vitamin D sufficiency, are warranted. Genotype-phenotype research efforts are
      also warranted.

PMID- 30099762
TI  - Biologically guided flap stability: the role of flap thickness including
      periosteum retention on the performance of the coronally advanced flap-A double
      blind randomized clinical trial.
AB  - AIM: To evaluate the possible benefit on wound healing and flap stability of
      periosteum inclusion, comparing a "split-full-split" thickness flap elevation
      versus a "split" thickness approach performed during CAF for the treatment of
      isolated-type gingival recessions in the upper jaw. MATERIAL AND METHODS: Forty
      patients were randomized, 20 were treated with "split-full-split" (test group)
      and 20 with a "split" approach (control group). Analysed parameters at 1 year
      were CRC, percentage of recession coverage (RC), keratinized tissue (KT) gain and
      patient-related outcome measurements. RESULTS: After 12 months, CRC was 80% in
      the test group and 35% in the control group. Percentages of RC and KT gain were
      higher in the test group, and a significant association between CRC and the
      thickness of the flap after elevation was found. Patient-related outcomes
      measurements were better for the test group. CONCLUSIONS: Flap thickness
      preservation and the presence of the periosteum in part of the flap may play a
      fundamental role in obtaining CRC.

PMID- 30099761
TI  - Upregulation of C/EBPbeta and TSC2 by an HDAC inhibitor CG200745 protects heart
      from DOCA-induced hypertrophy.
AB  - Histone deacetylases (HDACs) are a vast family divided into four major classes:
      class I (1, 2, 3, and 8), class II (4, 5, 6, 7, 9 and 10), class III (sirtuin
      family) and class IV (HDAC11). HDAC inhibition attenuates cardiac hypertrophy
      through suppression of the mechanistic target of rapamycin complex1 (mTORC1)
      signaling. HDAC inhibitors upregulate the expression of tuberous sclerosis
      complex 2 (TSC2), an mTORC1 inhibitor. However, the molecular mechanism
      underlying HDAC inhibitor-mediated upregulation of TSC2 is unclear. We
      hypothesized that an HDAC inhibitor, CG200745 (CG), ameliorates cardiac
      hypertrophy through the inhibition of mTORC1 signaling by upregulating of the
      CCAAT/enhancer-binding protein-beta (C/EBP-beta)/TSC2 pathway. To establish a
      cardiac hypertrophy model, deoxycorticosterone acetate (DOCA, 40 mg/kg/wk) was
      subcutaneously injected for 4 weeks into Sprague-Dawley rats. All rats were
      unilaterally nephrectomized and had free access to drinking water containing 1%
      NaCl with or without CG of different concentrations. The expression level of TSC2
      and C/EBP-beta was measured by quantitative real-time PCR (qRT-PCR) and western
      blot analysis. Acetylation of C/EBP-beta was analyzed by immunoprecipitation. The
      recruitment of C/EBP-beta and polymerase II (Pol II) on TSC2 promoter region was
      analyzed by chromatin immunoprecipitation (ChIP). CG treatment increased the
      expression of TSC2. In addition, CG treated rats showed an increased in the
      expression and acetylation of C/EBP-beta, owing to the increase in the
      recruitment of C/EBP-beta and Pol II at Tsc2 gene promoter. Thus, CG ameliorates
      cardiac hypertrophy through the inhibition of mTORC1 signaling via upregulation
      of the C/EBP-beta/TSC2 pathway in DOCA-induced hypertensive rats.

PMID- 30099763
TI  - Self-reported oral health predicts tooth loss after five and ten years in a
      population-based study.
AB  - AIM: To assess the suitability of self-reported oral health status to predict 5-
      and 10-year tooth loss without involvement of any clinical measures. MATERIALS
      AND METHODS: Within the population Study of Health in Pomerania (SHIP), 2,776
      subjects with 5-year follow-up data and 2,016 subjects with 10-year follow-up
      examination data were studied. Self-rated oral health was assessed at baseline
      and related to 5- and 10-year tooth loss. Odds ratios and probability of loss
      were estimated. RESULTS: Five- and 10-year tooth loss was significantly
      associated with baseline self-rated oral health. The predictive value of oral
      health ratings for tooth loss was comparable to that of the CDC/AAP case
      definition or caries and periodontitis diagnostics. In regression analyses
      including age, sex, smoking, education, income, and further items collected from
      questionnaires, odds ratios for dichotomous tooth loss associated with rating of
      oral health as poor were 3.04 (95% CI: 2.43-3.82) and 2.80 (2.11-3.71) after 5
      and 10 years, respectively. Prediction with cut-off probability at 0.25 resulted
      in sensitivity 85.8% and specificity 44.2% for 5 years, and that with cut-off
      probability at 0.40 resulted in sensitivity 83.5% and specificity 46.5% for 10
      years. CONCLUSION: Self-reported oral health provides reliable predictions of
      tooth loss comparable to those assessed by clinical diagnostics.

PMID- 30099764
TI  - Prediction of protein flexibility using a conformationally restrained contact
      map.
AB  - Knowledge of protein flexibility is crucial to understanding protein function.
      However, probing protein flexibility by either experiment or computational
      simulations is a difficult process. In particular, many computational approaches
      to understanding protein flexibility require an experimentally determined protein
      structure. The Conformationally Restrained Contact Map (CoRe-CMap) approach
      reported here couples protein disorder predictions with protein structure
      predictions and only requires sequence data to predict protein flexibility. This
      paper reports the application of the CoRe-CMap model to predicting Lipari-Szabo
      order parameters of all proteins for which experimentally derived Lipari-Szabo
      order parameters are available in the BioMagResBank: the median root mean square
      deviation between a protein's predicted and experimentally derived order
      parameters is 0.124. Additionally, application of the CoRe-CMap model to predict
      Lipari-Szabo order parameters for the 10th Type III Domain in Fibronectin and a
      homologous domain from Tenascin demonstrates the ability of CoRe-CMap to predict
      functionally important differences in protein flexibility.

PMID- 30099765
TI  - Deformation imaging of the atria using 2D strain: A noninvasive modality to
      characterize operating compliance?
AB  - This viewpoint with two illustrated case summaries of biventricular and biatrial
      mechanical function/dysfunction emphasizes the importance of continued research
      in deformation imaging beyond the left ventricle, as there are no Cinderellas in
      the heart and we just cannot afford to be nonchalant toward the atria,
      particularly the right atrium.

PMID- 30099766
TI  - Risk factors for reduced bone mineral density measurements in milk-allergic
      patients.
AB  - BACKGROUND: Earlier studies noted that young adults with IgE-mediated cow's milk
      allergy (IgE-CMA) have significantly lower bone mineral density (BMD) than age-
      and gender-matched controls. We sought to identify additional risk factors
      contributing to the low BMD in IgE-CMA patients. METHODS: Postpubertal (defined
      by Tanner stage V) IgE-CMA patients (n = 78; 16- to 30-year-old females and 17.5-
      to 30-year-old males) were evaluated prospectively for BMD using a DXA scan,
      serum values of bone turnover factor, and dietary and lifestyle questionnaires.
      Patients receiving > 2 short courses of systemic steroid treatments were
      excluded. RESULTS: Abnormal BMD measurements (T- or Z-scores < -1.0) of the
      lumbar vertebrae, femoral neck, or hip were noted in 60 patients, while normal
      BMD values were present in 18 patients, despite similarly decreased calcium
      intakes between the groups (P = 0.92). Patients with abnormal BMD were more
      likely to be asthmatic (P = 0.014), have a lower weight z-score (P = 0.007), have
      a decreased percent caloric intake derived from fat (P = 0.01), and have an
      increased carbohydrate intake (P = 0.03), in comparison with the normal-BMD
      group. Serum values of bone turnover were similar between the groups. On
      multivariate regression analysis, only asthma significantly (P = 0.006) increased
      the risk for osteopenia and osteoporosis (OR 38.5, 95% CI 2.8-500). Fitting
      continuous z-scores into a regression model, both asthma and weight z-score were
      significant (adjusted r2  = 0.272). Asthma was significantly overrepresented in
      osteopenic and osteoporotic subpopulations while decreased weight only in
      patients with osteoporosis. CONCLUSIONS: In the context of a low calcium intake,
      asthma and weight are independent risk factors for decreased BMD in IgE-CMA
      patients.

PMID- 30099767
TI  - Simultaneous Longitudinal Examination of Hopelessness, Thwarted Belongingness,
      and Perceived Burdensomeness as Predictors of Suicide Ideation.
AB  - OBJECTIVE: Based on Beck's hopelessness model (Beck, Kovacs, & Weissman, Journal
      of the American Medical Association, 234, 1975, 1146) and Joiner's (Why people
      die by suicide, 2005, Harvard University Press, Boston, MA) interpersonal theory
      of suicide, this study simultaneously examined three cognitive risk factors
      (hopelessness, thwarted belongingness, and perceived burdensomeness) as
      predictors of suicide ideation. METHOD: The study focused on high school and
      college students (ns = 192 and 142, respectively), assessed twice 4 months apart.
      RESULTS: When hopelessness, perceived burdensomeness, and thwarted belongingness
      were examined separately, each cognitive risk factor predicted future suicide
      ideation in both groups. When the three cognitions were tested simultaneously,
      none emerged as uniquely predictive of suicide ideation. A longitudinal, latent
      variable model suggested that a common factor underlying all three types of
      cognition significantly predicted suicide ideation. Furthermore, thwarted
      belongingness predicted both hopelessness and perceived burdensomeness over time.
      CONCLUSIONS: Results suggest ways that aspects of Beck's and Joiner's theories
      complement each other and could be combined to yield a more comprehensive
      understanding of cognitive factors associated with suicide ideation.

PMID- 30099768
TI  - Giant coronary artery aneurysms in an infant with Kawasaki disease: Evaluation by
      echocardiography and computed tomographic angiography.
AB  - Kawasaki disease (KD) is a vasculitis that affects medium-sized arteries and can
      lead to coronary artery aneurysms. KD should be considered in any infant
      presenting with prolonged fever. Delaying treatment beyond Day 10 of fever
      portends a high risk of coronary artery aneurysms. Echocardiography is often
      necessary to diagnose KD in young infants who frequently present without classic
      physical examination findings. We report on a case of KD with giant aneurysms in
      a 2-month-old infant. A combination of transthoracic echocardiography and CT
      angiography was utilized in the diagnosis as well as in the management of this
      infant.

PMID- 30099769
TI  - Standardized intraoperative application of an absorbable polysaccharide
      hemostatic powder to reduce the incidence of lymphocele after kidney
      transplantation - a prospective trial.
AB  - We assessed whether standardized application of an absorbable polysaccharide
      hemostatic powder (HaemoCerTM) has an effect on lymphocele rate after kidney
      transplantation. For this nonrandomized prospective trial, we first aimed to know
      our center-specific lymphocele rate diagnosed by ultrasound imaging. We
      retrospectively assessed all patient records of the elapsed year resulting in a
      center-specific rate of 20%, this was consistent with literature. The power
      analysis showed that 108 patients were required to detect a 50% reduction in
      lymphocele rate. During the prospective study period, 155 patients undergoing
      kidney transplantation were recruited to receive HaemoCerTM intraoperatively. In
      two patients, the product accidentally was not used. Six patients were excluded
      from analysis because of failure to complete follow-up (one early death and five
      early graft failures). Of the remaining 147 patients, 15 developed lymphoceles,
      which represents a rate of 10.2%; (95% CI: 6.3-16.2%). Compared to the expected
      occurrence, this was significantly lower (P = 0.003). Lymphoceles appeared to be
      associated with preoperative donor-specific antibody, retransplantation and
      immunoadsorption in HLA or ABO incompatible donors. At our institution, the
      frequency of lymphoceles after kidney transplantation appeared to be
      significantly reduced when HaemoCerTM was applied routinely. The magnitude of the
      effect warrants randomized evaluation.

PMID- 30099770
TI  - Decorin promotes proliferation and migration of ORS keratinocytes and maintains
      hair anagen in mice.
AB  - DECORIN is a prototypical member of the small leucine-rich proteoglycan (SLRP)
      family that plays important roles in numerous biological processes and cellular
      biological pathways. We previously showed that Decorin expression was highly
      enhanced in mouse dorsal hair follicles (HFs) during the anagen phase and was
      reduced during the catagen and telogen phases, suggesting that Decorin might
      modulate follicular cycling and morphogenesis. In this study, to further clarify
      the effects of DECORIN on hair cells and the cycling transition, an in vitro
      overexpression strategy and Decorin-null (Dcn-/- ) mice were used to investigate
      the effects of DECORIN on outer root sheath (ORS) keratinocytes. DECORIN
      overexpression significantly enhanced proliferation and migration in ORS
      keratinocytes in vitro. Moreover, DECORIN overexpression upregulated the mRNA and
      protein expression levels of WNT10b, beta-CATENIN and LEF1. The DECORIN
      overexpression-induced increase in the proliferation and migration of ORS
      keratinocytes was partially inhibited by a Wnt/beta-catenin inhibitor.
      Furthermore, Dcn-/- mice had a shortened anagen phase and lower levels of beta
      catenin expression than were observed in wild-type mice in imaging and
      histological analyses. Taken together, these findings suggest that DECORIN
      promotes the proliferation and migration of ORS keratinocytes in vitro and
      maintains hair anagen in mice.

PMID- 30099771
TI  - Cervical transposition test using Hegar dilator at oestrus as a tool to select
      ewes for transcervical embryo collection.
AB  - This study evaluated the cervical transposition method as a tool to select ewes
      for embryo collection by transcervical route. Adult Santa Ines ewes (n = 50)
      received Day 0 protocol for superovulation treatments. The cervix transposition
      test was performed both at oestrus and at the embryo collection time. The latter
      was preceded by hormonal cervical dilation. The sensitivity, specificity,
      positive predictive value, negative predictive value and accuracy were 85.7%,
      66.6%, 85.7%, 66.6% and 80.0%, respectively. The kappa index yielded a moderate
      score (kappa = 0.52). In conclusion, the high sensitivity and accuracy indicate
      that the cervical transposition test is a screening option to select ewes for
      embryo collection by transcervical route.

PMID- 30099772
TI  - Interleukin-1 receptor antagonist as a biomarker of sepsis in neutropenic
      haematological patients.
AB  - OBJECTIVE: The study aim was to compare the performance of interleukin-1 receptor
      antagonist (IL-1Ra) to C-reactive protein (CRP) and procalcitonin (PCT) in early
      prediction of the clinical course of febrile neutropenia. METHODS: The study
      population consisted of 86 consecutive patients with febrile neutropenia who
      received intensive chemotherapy for haematological malignancy between November
      2009 and November 2012 at the adult haematology ward of Kuopio University
      Hospital. Twenty-three (27%) patients had acute myeloid leukaemia and 63 (73%)
      patients were autologous stem cell transplant recipients. IL-1Ra, CRP and
      procalcitonin were measured at the onset of fever (d0), on day 1 (d1) and on day
      2 (d2). RESULTS: Eight patients developed severe sepsis, including three patients
      with septic shock. Eighteen patients had bacteraemia. After the onset of febrile
      neutropenia Youden's indices (with their 95% confidence intervals) to identify
      severe sepsis were for IL-1Ra on d0 0.57 (0.20-0.71) and on d1 0.65 (0.28-0.78),
      for CRP on d0 0.41 (0.04-0.61) and on d1 0.47 (0.11-0.67) and for PCT on d0 0.39
      (0.05-0.66) and on d1 0.52 (0.18-0.76). CONCLUSIONS: In haematological patients,
      IL-1Ra has a comparable capacity with CRP and PCT to predict severe sepsis at the
      early stages of febrile neutropenia.

PMID- 30099773
TI  - The Firepower Sweep Test: A novel approach to cookstove laboratory testing.
AB  - Emissions from solid-fuel cookstoves have been linked to indoor and outdoor air
      pollution, climate forcing, and human disease. Although task-based laboratory
      protocols, such as the Water Boiling Test (WBT), overestimate the ability of
      improved stoves to lower emissions, WBT emissions data are commonly used to
      benchmark cookstove performance, estimate indoor and outdoor air pollution
      concentrations, estimate impacts of stove intervention projects, and select
      stoves for large-scale control trials. Multiple-firepower testing has been
      proposed as an alternative to the WBT and is the basis for a new standardized
      protocol (ISO 19867-1:2018); however, data are needed to assess the value of this
      approach. In this work, we (a) developed a Firepower Sweep Test [FST], (b)
      compared emissions from the FST, WBT, and in-home cooking, and (c) quantified the
      relationship between firepower and emissions using correlation analysis and
      linear model selection. Twenty-three stove-fuel combinations were evaluated. The
      FST reproduced the range of PM2.5 and CO emissions observed in the field,
      including high emissions events not typically observed under the WBT. Firepower
      was modestly correlated with emissions, although the relationship varied between
      stove-fuel combinations. Our results justify incorporating multiple-firepower
      testing into laboratory-based protocols but demonstrate that firepower alone
      cannot explain the observed variability in cookstove emissions.

PMID- 30099774
TI  - Treatment of recurrent isolated right atrial metastatic cavitary mass from breast
      cancer with radiation therapy: A case report and review of literature.
AB  - The heart is a destination for metastases of various types of primary tumors,
      with lung, breast, melanoma, and mesothelioma being the most common types.
      Recurrent isolated cardiac metastasis presenting as a cavitary mass is rare. We
      present a case of recurrent isolated cavitary metastatic mass to the right atrium
      in a patient with the history of breast cancer who presented with new-onset
      atrial fibrillation. The patient successfully received radiation therapy with the
      resolution of the mass confirmed on repeat echocardiography.

PMID- 30099775
TI  - High-throughput prediction of disordered moonlighting regions in protein
      sequences.
AB  - Intrinsically disordered regions lack stable structure in their native
      conformation but are nevertheless functional and highly abundant, particularly in
      Eukaryotes. Disordered moonlighting regions (DMRs) are intrinsically disordered
      regions that carry out multiple functions. DMRs are different from moonlighting
      proteins that could be structured and that are annotated at the whole-protein
      level. DMRs cannot be identified by current predictors of functions of disorder
      that focus on specific functions rather than multifunctional regions. We
      conceptualized, designed and empirically assessed first-of-its-kind sequence
      based predictor of DMRs, DMRpred. This computational tool outputs propensity for
      being in a DMR for each residue in an input protein sequence. We developed novel
      amino acid indices that quantify propensities for functions relevant to DMRs and
      used evolutionary conservation, putative solvent accessibility and intrinsic
      disorder derived from the input sequence to build a rich profile that is suitable
      to accurately predict DMRs. We processed this profile to derive innovative
      features that we input into a Random Forest model to generate the predictions.
      Empirical assessment shows that DMRpred generates accurate predictions with area
      under receiver operating characteristic curve = 0.86 and accuracy = 82%. These
      results are significantly better than the closest alternative approaches that
      rely on sequence alignment, evolutionary conservation and putative disorder and
      disorder functions. Analysis of abundance of putative DMRs in the human proteome
      reveals that as many as 25% of proteins may have long >30 residues) DMRs. A
      webserver implementation of DMRpred is available at
      http://biomine.cs.vcu.edu/servers/DMRpred/.

PMID- 30099776
TI  - Adenomatoid tumour of the uterus is frequently associated with iatrogenic
      immunosuppression.
AB  - AIMS: Uterine adenomatoid tumour (AT) is a benign proliferation of cells showing
      mesothelial differentiation within the myometrium that usually presents as a
      single nodule. Rare diffuse uterine ATs have been reported, often in patients
      undergoing immunosuppressive therapy. Herein, we aimed to elucidate the general
      association between the incidence of uterine AT and iatrogenic immunosuppression
      by cohort analysis. METHODS AND RESULTS: We analysed 611 consecutive hysterectomy
      specimens to determine the incidence of AT and its correlation with the
      immunosuppressive status. Mesothelial lineage, p16 expression, mismatch repair
      (MMR) protein alterations, and the possible integration of tumorigenic viruses
      were examined by in situ hybridizasion and immunohistochemistry. ATs were
      detected in 14 of 611 hysterectomy cases (2.3%). The incidence of AT was
      significantly higher in the immunosuppressed (IS) group (5/20, 25.0%) than in the
      non-IS group (9/591, 1.52%), with a relative risk of 16.4. Of the five ATs in the
      IS group, three were multifocal or diffuse. Latent uterine AT was detected, by in
      toto sectioning, in one of four immunosuppressed autopsy cases. The tumor cells
      of ATs commonly expressed calretinin and podoplanin. Characteristic block-type
      (>=90%) positivity for p16 was observed in most ATs. None of the ATs were
      positive for human herpes virus type 8, Merkel cell polyomavirus, SV40 large T
      antigen, Epstein-Barr virus, and human papilloma virus, and the MMR proteins were
      retained. A TRAF7 mutation was identified from macrodissected tissue in one of 12
      ATs by Sanger sequencing. CONCLUSION: Uterine AT is an immunosuppression
      associated mesothelial lesion characterised by p16 overexpression.

PMID- 30099777
TI  - Differential expression of lncRNAs and predicted target genes in normal mouse
      melanocytes and B16 cells.
AB  - Melanoma is a highly invasive and metastatic malignant skin tumor with poor
      prognosis. Although several widely studied pure melanoma cell lines are
      available, the precise mechanism underlying transformation of melanocyte to
      melanoma remains unclear. Long non-coding RNAs (lncRNAs) represent a vast
      category of non-coding RNA molecules, and increasing evidence suggests that
      lncRNAs are crucial for various biological processes, including those in the
      skin. Herein, lncRNA sequencing was performed on an Illumina HiSeq platform to
      identify lncRNAs expressed differently in murine B16 melanoma cells compared to
      normal mouse melanocytes. Using four computational approaches, 2319 lncRNAs were
      expressed in both normal melanocytes and B16 cells, with 373 being differentially
      expressed at a significant level. Of these, 136 lncRNAs were upregulated and 237
      were downregulated. KEGG analyses revealed that 467 genes were target genes in
      the Wnt signalling pathway, TGF-beta signalling pathway, MAPK signalling pathway,
      NF-kappa B signalling pathway, melanoma and several other cancer-related
      regulatory pathways. From among the differentially expressed lncRNAs, lnc-13317.1
      was found to play a role in the cell cycle in melanoma by targeting BRCA1. Thus,
      lnc-13317.1 might have therapeutic potential in melanoma treatment. The lncRNA
      profile described here highlights the importance of elucidating the exact
      function of these lncRNAs in the transformation of melanoma. Lnc-13317.1 might
      have therapeutic potential in melanoma treatment by targeting BRCA1.

PMID- 30099778
TI  - Rumination, Brooding, and Reflection: Prospective Associations with Suicide
      Ideation and Suicide Attempts.
AB  - OBJECTIVE: Rumination is often cited as a risk factor for suicide, yet few
      studies of rumination have utilized clinical samples, and no studies have
      examined its prospective association with suicide attempts. The purpose of this
      study was to examine concurrent and prospective associations of brooding and
      reflection (the two components of rumination) with suicide ideation and suicide
      attempts among a high-risk clinical sample. METHOD: Participants were 286
      adolescents and young adults (77% Caucasian, 59% female) aged 13-25 seeking
      psychiatric emergency services. A majority (71%) were presenting with a primary
      complaint of suicide ideation or recent suicide attempt. Participants completed a
      baseline assessment at the index visit; 226 participants (79%) completed a 4
      month follow-up assessment of suicidal thoughts and behaviors. RESULTS: Brooding
      was associated with lifetime history of one or more suicide attempts, but not
      concurrent suicide ideation. Reflection was not associated with lifetime suicide
      attempts or concurrent suicide ideation. Furthermore, prospective associations of
      brooding and reflection with suicide ideation and suicide attempts were weak-to
      small in magnitude and statistically nonsignificant. CONCLUSIONS: Rumination
      appears to have a limited association with suicide-related outcomes within a high
      risk clinical sample. Additional longitudinal studies utilizing clinical samples
      are critically needed to better understand these associations.

PMID- 30099780
TI  - Frailty has a significant influence on postoperative complications after kidney
      transplantation-a prospective study on short-term outcomes.
AB  - Currently, there are no tools to predict postsurgery outcome after kidney
      transplantation. This study assesses whether frailty influence 30-day
      postoperative complications after kidney transplantation. One-hundred and fifty
      kidney transplantations were prospectively included. Frailty was assessed using a
      frailty indicator, consisting of 15 questions, covering most domains of
      functioning. Postoperative complications were measured by the Comprehensive
      Complication Index (CCI). Using a linear regression model, 30-day postoperative
      complications and frailty correlation were adjusted for confounders, including
      sex, age, ASA Score, Charlson Comorbidity Index, hypertension, BMI, smoking,
      dialysis, duration of dialysis, type of transplantation, and retransplantation.
      The mean frailty score was 2.07(+/-1.6) and 23 patients were classified as frail
      (GFI >=4). The mean CCI-score was 18(+/-15.6), the mean CCI-score for "frail"
      patients 30.1(+/-17.2) compared to 15.5 (+/-14.2) for "non-frail" patients (N =
      116). In a regression analysis, a significant relationship between CCI-score and
      frailty (beta = 13.3; 95% CI 5.7-20.9; P = 0.0007) and transplantation type (beta
      = 4.9; 95% CI: 0.72-9.16; P = 0.02) was found, independent of confounders. In
      conclusion, frailty and type of transplantation are independent factors
      associated with an increased risk of postoperative complications.

PMID- 30099779
TI  - The role of environmental factors in allergy: A critical reappraisal.
AB  - Allergies are usually referred to as type I hypersensitivity reactions against
      innocuous environmental antigens, characterized by a Th2/IgE-dominated
      inflammation. They can manifest themselves in various organs, such as skin,
      gastrointestinal and respiratory tract, and comprise diseases as diverse as
      allergic rhinitis and conjunctivitis, bronchial asthma, oral allergy syndrome,
      food allergy, urticaria and atopic eczema, but also anaphylactic shock. Within
      the last decades, there was a significant global increase in allergy prevalence,
      which has been mostly attributed to changes in environment and lifestyle. But
      which, among all factors discussed, are the most relevant, and what are the
      mechanisms by which these factors promote or prevent the development of allergic
      diseases? To answer this, it is necessary to go back to the two key questions
      that have occupied allergy researchers for the last decades: Firstly, what makes
      an allergen an allergen? Secondly, why are more and more individuals affected?
      Within the last decade, we have made considerable progress in answering these
      questions. This review gives an overview over scientific progress in the field,
      summarizes latest findings and points out future prospective and research needs.

PMID- 30099782
TI  - Disorders of sex development in cats with different complements of sex
      chromosomes.
AB  - The genetic background of disorders of sex development (DSDs) in cats is poorly
      understood, due to a relatively low number of such studies in this species. Here
      we present three new DSD cases with different complements of sex chromosomes. The
      first, an Oriental Shorthair cat with a rudimentary penis, abdominal atrophic
      testicles and lack of uterus appeared to be a freemartin, since leucocyte
      chimerism XX/XY and a lack of Y-linked genes (SRY and ZFY) were observed in DNA
      isolated from hair follicles. XXY trisomy was identified in the second case, a
      tortoiseshell Devon Rex male cat with atrophic scrotal testicles and a normal
      penis. Finally, a European Shorthair cat with atrophic testicles in a bifid
      scrotum, rudimentary penis and a lack of uterus had XY complement, including Y
      chromosome of normal size and morphology. Also presence of eight Y-linked genes,
      detected by PCR, was confirmed. Due to the low testosterone level in this last
      patient, we searched for a causative mutation in two candidate genes (HSD3B2 and
      HSD17B3) involved in the metabolism of this steroid hormone. Altogether, five
      polymorphic sites in HSD3B2 and two in HSD17B3 were found, but none of them
      showed associations with DSD phenotype. We thus excluded a possibility that the
      causative mutation is present in these genes. In conclusion, we confirmed that
      analysis of the sex chromosome complement is a crucial step in diagnosis of DSDs.
      However, extensive molecular studies of the genes involved in sex development are
      needed to elucidate the causes of DSDs in cats with normal complements of sex
      chromosomes.

PMID- 30099783
TI  - In vitro rumen fermentation, microbial protein synthesis and composition of
      microbial community of total mixed rations replacing maize silage with red clover
      silage.
AB  - This study aimed to evaluate in vitro fermentation characteristics, microbial
      protein synthesis and microbial community composition when replacing maize silage
      (MS) with red clover silage (RCS) in total mixed rations (TMR) of dairy cows.
      Treatments included TMR containing forage (MS and RCS) and concentrates
      (0.75:0.25) with targeted proportions (dry matter (DM) basis) of RCS in TMR of
      0.15 (RCS15 ), 0.30 (RCS30 ), 0.45 (RCS45 ), and 0.60 (RCS60 ), in substitution
      of MS. Samples of the TMR were incubated using the in vitro Ankom RF technique
      with a mixture of rumen fluid and buffer solution (1:2 v/v) for 8 and 24 hr. Gas
      production and total short-chain fatty acids concentration did not differ between
      diets, whereas ammonia-nitrogen concentration increased with increasing level of
      RCS. Acetate proportion was not affected by RCS level, but propionate showed a
      linear increase with increasing level of RCS at the expenses of butyrate.
      Branched fatty acids proportions linearly declined, reflecting a reduced
      deamination of true protein. Gene copy numbers of protozoa linearly decreased
      with increasing RCS levels, while total numbers of bacteria and methanogens were
      not affected by diet. The amylolytic bacteria Ruminobacter amylophillus and
      Prevotella bryantii showed evidence to increase with higher RCS levels after 8 hr
      and 24 hr, respectively, whereas no effects of diet where observed for the
      fibrolytic bacteria Ruminococcus albus, Ruminococcus flavefaciens and Fibrobacter
      succinogenes. Concentrations of purine bases, and total N production in liquid
      associated microbes declined with increasing RCS levels, suggesting a negative
      impact of this feed on microbial growth. The findings of this study suggest that
      in general, microbial protein synthesis might be impaired by the substitution of
      MS by RCS, therefore caution should be taken when formulating diets for dairy
      cows using high levels of RCS as ingredient.

PMID- 30099784
TI  - Determination of the gestational age through ultrasound measurements of some
      uterine and foetal parameters in Bulgarian local goats.
AB  - The aim of the current study was to determine the gestational age in goats
      through the measurement of some foetal and uterine structures. Twenty-four
      pregnant Bulgarian local goats were submitted to ultrasound foetometry by
      transrectal and transabdominal approaches. Ultrasound measurement of studied
      parameters was done at 7-day intervals during the first trimester of gestation
      (days 21-49) and at 14-day intervals between gestation days 49 and 133.
      Associations of foetometry data with foetal age were investigated by linear (y =
      a + bx), quadratic (y = ax2  + bx + c) and exponential (y = axn ) equations.
      According to the results, some biometric parameters (uterine lumen diameter,
      crown-rump length, trunk diameter, biparietal diameter, foetal aortic diameter)
      exhibited a stronger correlation to gestational age (R2  >= 0.90) and lower
      standard error of the estimate (SEE <= 8) as compared to foetal eye orbit
      diameter, and outer and inner placentome diameters (R2  <= 0.90; SEE >= 8). Each
      of these biometric parameters could be measured in different periods of
      gestation, thus allowing for monitoring and determination of foetal age at almost
      all stages of pregnancy.

PMID- 30099781
TI  - Racial disparities in preemptive referral for kidney transplantation in Georgia.
AB  - BACKGROUND: Racial disparities persist in access to kidney transplantation.
      Racial differences in preemptive referral, or referral prior to dialysis start,
      may explain this discrepancy. METHODS: Patient-level data on kidney transplant
      referrals (2005-2012) from all Georgia transplant centers were linked to the
      United States Renal Data System to examine racial disparities in preemptive
      referral, waitlisting, and living donor transplant. Adjusted logistic regression
      and Cox proportional hazard models determined the associations between race
      (African American vs white) and preemptive referral, and placement on the
      waitlist and receipt of a living donor kidney, respectively. RESULTS: Among 7752
      adults referred for transplant evaluation, 20.38% (n = 1580) were preemptively
      referred. The odds of African Americans being preemptively referred for
      transplant evaluation were 37% (OR = 0.63; [95% CI: 0.55 0.71]) lower than white
      patients. Among preemptively referred patients, there was no racial difference
      (African Americans compared to white patients. HR = 0.96; [95% CI: 0.88, 1.04])
      in waitlisting. However, African Americans were 70% less likely than white
      patients to receive a living donor transplant (HR = 0.30; [95% CI: 0.21, 0.42]).
      CONCLUSION: Racial disparities in transplant receipt may be partially explained
      by disparities in preemptive referral. Interventions to reduce racial disparities
      in kidney transplant access may need to be targeted earlier in the disease
      process.

PMID- 30099785
TI  - Homogenization-resistant spermatids in testicular tissue stored under suboptimal
      conditions-Effect of time and temperature.
AB  - Reproductive assessments on wild animals are often hampered due to practical
      problems during sample collection. For example, the time between death and tissue
      collection as well as sample storage conditions will affect the quality of the
      tissue. The aim of this study was to examine the effect of less optimal, field
      like conditions, that is different temperatures and variable storage time, on the
      quantification of homogenization-resistant spermatids in testicular tissue, using
      the bull as a model. One bull testis was kept in +5 degrees C for 216 hr, from
      which (n = 68) samples were taken at different time points for storage in -20
      degrees C or +21 degrees C. Some samples were frozen, thawed and then refrozen.
      The tissue was homogenized, and the number of spermatids was quantified manually
      with a counter chamber. Compared to the samples taken at 0 hr, the number of
      spermatids was unchanged until 120 hr storage in +5 degrees C and in frozen
      samples from the same time-point. After 72-hr storage in room temperature, there
      was a marked drop in the number of spermatids. Refreezing of samples resulted in
      a markedly lower number of spermatids. Frozen samples did not have significantly
      decreased numbers of spermatids compared to refrigerated samples. In conclusion,
      different storage conditions do not seem to affect the spermatids resistance to
      homogenization until day 3, but if kept in cool conditions it is possible to use
      samples up until 5 days of storage. The method is a good choice for suboptimal
      sampling conditions.

PMID- 30099786
TI  - Granulocyte-macrophage colony-stimulating factor improves mouse peripheral nerve
      regeneration following sciatic nerve crush.
AB  - Peripheral nerve injuries severely impair patients' quality of life as full
      recovery is seldom achieved. Upon axonal disruption, the distal nerve stump
      undergoes fragmentation, and myelin breaks down; the subsequent regeneration
      progression is dependent on cell debris removal. In addition to tissue clearance,
      macrophages release angiogenic and neurotrophic factors that contribute to axon
      growth. Based on the importance of macrophages for nerve regeneration, especially
      during the initial response to injury, we treated mice with granulocyte
      macrophage colony-stimulating factor (GM-CSF) at various intervals after sciatic
      nerve crushing. Sciatic nerves were histologically analyzed at different time
      intervals after injury for the presence of macrophages and indicators of
      regeneration. Functional recovery was followed by an automated walking track
      test. We found that GM-CSF potentiated early axon growth, as indicated by the
      enhanced expression of growth-associated protein at 7 days postinjury. Inducible
      nitric oxide synthase expression increased at the beginning and at the end of the
      regenerative process, suggesting that nitric oxide is involved in axon growth and
      pruning. As expected, GM-CSF treatment stimulated macrophage infiltration, which
      increased at 7 and 14 days; however, it did not improve myelin clearance.
      Instead, GM-CSF stimulated early brain-derived neurotrophic factor (BDNF)
      production, which peaked at 7 days. Locomotor recovery pattern was not improved
      by GM-CSF treatment. The present results suggest that GM-CSF may have beneficial
      effects on early axonal regeneration.

PMID- 30099787
TI  - Relationship of cysteine-rich secretory protein-3 gene and protein with semen
      quality in stallions.
AB  - Cysteine-rich secretory protein-3 (CRISP-3) and some of its nonsynonymous
      polymorphism have been related to the fertility and freezability of stallion
      semen; however, the role of the CRISP-3 gene and its seminal plasma protein in
      the raw semen quality is still unknown. The aim of this study was to evaluate the
      relationship of CRISP-3 with semen quality in stallions. DNA was obtained from
      blood samples of 100 stallions, from which 30 stallions were randomly selected to
      obtain 60 ejaculates. Through PCR amplification and sequencing, the variation of
      four nonsynonymous SNPs from CRISP-3 was identified and haplotypes were derived.
      Semen quality was assessed through the total motility (MOT), sperm vitality (SV),
      normal morphology (NM), functional integrity of membrane (MI) and a seminal
      quality index (SQi). CRISP-3 protein content of seminal plasma (SP) was
      determined by ELISA. The effect of the genotype, the haplotype and the
      concentration of the CRISP-3 protein on the seminal quality were evaluated
      through generalized linear models and linear regression analyses. Homozygous
      genotypes for SNP1, SNP2 and SNP3 and the heterozygous genotype for SNP4 showed a
      positive effect on seminal quality. Different haplotypes with positive effect on
      MOT, SV, NM, MI and SQi were identified. The allelic substitution analysis
      resulted in positive regression coefficients for MOT (SNP2) and MI (SNP2 and
      SNP3). A high level of CRISP-3 resulted in a higher MOT and SQi. It is concluded
      that the quality of stallion semen is influenced by the genotype of CRISP-3 and
      the concentration of CRISP-3 protein in SP.

PMID- 30099790
TI  - Neuroscience without borders: Preserving the history of neuroscience.
AB  - Over the last 50 years, neuroscience has enjoyed a spectacular development, with
      many discoveries greatly expanding our knowledge of brain function. Despite this
      progress, there has been a disregard for preserving the history of these
      discoveries. In many European countries, historic objects, instruments, and
      archives are neglected, while libraries and museums specifically focusing on
      neuroscience have been closed or drastically cut back. To reverse this trend, the
      Federation of European Neuroscience Societies (FENS) has organized a number of
      projects, including (a) the History of Neuroscience online projects, (b) the
      European Brain Museum Project (EBM), (c) the History online library, (d) the FENS
      meeting History Corner, (e) history lectures in historic venues, and (f) a series
      of history seminars in various European venues. These projects aim to stimulate
      research in, and increase awareness of, the history of European neuroscience. Our
      seminars have attracted large audiences of students, researchers, and the general
      public, who have supported our initiatives for the preservation of the history of
      neuroscience for future generations and for the promotion of interest in the
      history of neuroscience. It is therefore urgent to develop new methods for
      preserving our history, not only in Europe but also in the rest of the world, and
      to increase greatly teaching and research in this important aspect of our
      scientific and cultural legacy.

PMID- 30099789
TI  - Investigation of Eph-ephrin A1 in the regulation of embryo implantation in sows.
AB  - Eph A1 and ephrin A1 (Eph-ephrin A1) is a key receptor-ligand pair of Eph-ephrin
      system, which plays important roles in the migration and adhesion of cells,
      tissue morphogenesis and vasculogenesis in mammals. In order to investigate the
      regulation of Eph-ephrin A1 during porcine embryo implantation, the expressions
      of mRNA and protein of Eph-ephrin A1 were detected in different reproductive
      tissues from twelve sows during embryo implantation period on pregnancy day 13,
      18 and 24, respectively. Functions of Eph-ephrin A1 on the migration and adhesion
      of porcine endometrial epithelial cells were analysed by RNA interference (RNAi),
      transwell migration assays and MTT assays. Results showed that mRNA levels of Eph
      ephrin A1 were highly expressed in endometrial attachment site when compared to
      other reproductive tissues (p < 0.05) and were peaked on pregnancy day 18 during
      embryo implantation (p < 0.05). Protein levels of Eph-ephrin A1 were highly
      expressed in endometrial attachment site and were peaked on pregnancy day 18 (p <
      0.05). Eph-ephrin A1 proteins were located in endometrial luminal epithelium,
      stroma of attachment site and inter-attachment site during embryo implantation,
      and the protein levels were higher during implantation compared to pre
      implantation or post-implantation. Furthermore, silencing ephrin A1 gene
      significantly reduced the migration and adhesion capacity of porcine endometrial
      epithelial cells. These findings suggest that the Eph-ephrin A1 protein likely
      targets endometrial attachment site to enhance the migration and adhesion of
      porcine endometrial epithelial cells around pregnancy day 18 during pregnancy in
      sows.

PMID- 30099788
TI  - Vitamin D status and risk of infections after liver transplantation in the Swiss
      Transplant Cohort Study.
AB  - Increasing evidence indicates a role of vitamin D in the immune system affecting
      response to infections. We aimed to characterize the role of vitamin D status,
      i.e. deficiency [25-OH vitamin D (25-OHD) <50 nmol/l] and no deficiency (25-OHD
      >=50 nmol/l) in incident infections after liver transplantation. In 135 liver
      transplant recipients, blood samples drawn at time of liver transplantation and 6
      months afterwards were used to determine 25-OHD levels. Incident infections
      episodes were prospectively collected within the Swiss Transplant Cohort Study
      database. Poisson regression was applied to address associations between vitamin
      D status and incident infections. Vitamin D deficiency was common at time of
      transplantation and 6 months afterwards without a significant change in median 25
      OHD levels. In univariable analyses, vitamin D deficiency was a risk factor for
      incident infections in the first 6 months post-transplant incidence rate ratio
      (IRR 1.52, 95% CI 1.08-2.15, P = 0.018) and for bacterial infections occurring
      after 6 up to 30 months post-transplant (IRR 2.29, 95% CI 1.06-4.94, P = 0.034).
      These associations were not detectable in multivariable analysis with adjustment
      for multiple confounders. Efforts to optimize vitamin D supplementation in liver
      transplant recipients are needed. Our data question the role of vitamin D
      deficiency in incident infections.

PMID- 30099792
TI  - Child participation in sports is influenced by patterns of lifestyle-related
      behaviors.
AB  - OBJECTIVES: The purpose of this study was to identify patterns of child and
      family characteristics and behaviors, and to determine the association of those
      patterns with child participation in sports. METHODS: A questionnaire and
      anthropometric measures were used to collect data on 834 parents and their 6- to
      10-year-old children. A principal component analysis identified child and
      parental patterns, which were tested for association with child participation in
      extracurricular sports (ES). RESULTS: Seven patterns were identified: (1) socio
      economic, (2) child obesity, (3) parental TV viewing, (4) father's physical
      activity (PA), (5) mother's PA, (6) child screen time, and (7) parental reported
      barriers. After adjustment, patterns 1 and 7 (P < .001), pattern 2 (P = .01), and
      patterns 5 and 6 (P = .04) were significantly associated with the number of
      sports practiced by children while, patterns 1 and 7 (P < .001), pattern 2 (P =
      .03), and patterns 4 and 5 (P = .01) were significantly associated with frequency
      of participation in ES. CONCLUSION: Future interventions to promote children's
      participation in sports should be based on a socio-ecological model and targeted
      to high-risk populations showing multiple risks such as a lower socio-economic
      status, inactive parents, or obese children.

PMID- 30099791
TI  - The first crystal structure of crustacean ferritin that is a hybrid type of H and
      L ferritin.
AB  - Ferritin, a ubiquitous iron storage protein, has a crucial role in innate
      immunity in arthropods, which have no adaptive immune system. Arthropods are
      thought to have two types of ferritin molecules: the secreted type and the
      cytosolic type. Here, we present the first crystal structure of ferritin from
      crustacean, kuruma prawn (Marsupenaeus japonicus), at 1.16 A resolution. This
      shrimp ferritin (MjFer) is the cytosolic type, and its structure shows well
      conserved ferritin fold composed of a 4-helix bundle that assembles into a cage
      like 24-mer. The structure of MjFer was more similar to those of human and
      vertebrate ferritins than to that of the secreted-type arthropod ferritin from an
      insect. MjFer possesses both a ferroxidase site and a nucleation site, which are
      the main characteristics of vertebrate H and L chain ferritins, respectively. The
      first crystal structure of crustacean ferritin, MjFer, has exceptionally high
      quality that provides the detailed structural information of metal moving pathway
      in ferritin.

PMID- 30099794
TI  - The influence of biological affinity and sex on morphometric parameters of the
      clavicle in a South African sample.
AB  - OBJECTIVES: The present study aims to investigate the influence of environmental
      and functional factors associated with biological affinity and musculature on
      sexual dimorphism of the clavicle, and to develop population-specific methods of
      sex estimation from the clavicle. METHODS: The maximum length of the clavicle
      (MAXL), the sagittal diameter of the clavicle (SAGD), and the vertical diameter
      of the clavicle (VERD) were measured. The left clavicles of 198 South African
      coloured individuals (108 males and 90 females) were examined. RESULTS: Overall,
      the results of this study indicate that the SAGD of the clavicle is more sexually
      dimorphic than the VERD in the South African coloured sample. When the black
      American, white American, and Greek discriminant functions were applied to the
      South African coloured metric data, females were more accurately classified than
      males overall. Population-specific discriminant functions were created for the
      South African coloured sample. The original accuracy showed that females (85.5%)
      were more accurately classified than males (78.1%). Overall, the multivariate
      discriminant function demonstrated a higher correct classification of South
      African coloureds than the univariate discriminant functions. The results also
      suggest that univariate discriminant function equations are more accurate for sex
      estimation than univariate sectioning points in the South African coloured
      sample. CONCLUSIONS: Overall, the results of the present study indicate that the
      clavicle is an accurate predictor of sex and its dimensions are population
      specific. Therefore, discriminant functions of the clavicle should only be used
      for sex estimation in forensic anthropology with the populations from which they
      were derived. (c) 2018 Wiley Periodicals, Inc.

PMID- 30099793
TI  - Identification of gibberellin-regulated protein as a new allergen in orange
      allergy.
AB  - BACKGROUND: To date, three orange allergens have been reported. However, it is
      still unclear whether gibberellin-regulated proteins (GRPs), identified as new
      allergens in other fruit allergies, are also involved in orange allergy.
      OBJECTIVE: To investigate the allergenicity of orange GRP and to determine the
      clinical characteristics of patients with orange allergy who are sensitized to
      orange GRP. METHODS: We enrolled 14 patients (four men, 10 women, mean age: 29.6
      years) who were diagnosed with orange allergy based on relevant clinical history,
      positive skin test, and/or positive challenge test. Orange GRP (molecular weight:
      6941.6 Da) was purified by ion-exchange column chromatography. To test for orange
      GRP-specific IgE, we performed ELISA, basophil activation tests, and skin prick
      tests. Cross-reactivity of orange GRP with native peach allergen nPru p 7 and
      Japanese apricot nPru m 7 was analysed by ELISA inhibition assays. IgE specific
      for orange, grapefruit, and peach allergens rPru p 1, rPru p 3, and rPru p 4 was
      measured using ImmunoCAP. RESULTS: Twelve of the 14 patients (85.7%) were
      positive for orange GRP allergy in at least one test: 71.4% (10/14) were positive
      by ELISA, 50% (3/6) were positive in the basophil activation test, and 100% (4/4)
      were positive in the skin prick test. ELISA inhibition assays revealed cross
      reactivity of orange GRP with both nPru p 7 and nPru m 7. The patients showed
      variable positivity for specific IgE against orange, grapefruit, rPru p 1, rPru p
      3, and rPru p 4 (57.1%, 71.4%, 7.1%, 0%, and 21.4%, respectively). The most
      frequent symptoms of orange GRP allergy were facial swelling and oropharyngeal
      symptoms. CONCLUSIONS AND CLINICAL RELEVANCE: Orange GRP may be involved in
      orange allergy and may be a cross-reactive allergen between citrus fruits and the
      Rosaceae family of fruits.

PMID- 30099795
TI  - Cell-based therapy for Parkinson's disease: A journey through decades toward the
      light side of the Force.
AB  - This review describes the history, development, and evolution of cell-based
      replacement therapy for Parkinson's disease (PD), from the first pioneering
      trials with fetal ventral midbrain progenitors to future trials using stem cells
      as well as reprogrammed cells. In the spirit of Tom Isaacs, the review takes
      parallels to the storyline of Star Wars, including the temptations from the dark
      side and the continuous fight for the light side of the Force. It is subdivided
      into headings based on the original movies, spanning from A New Hope to the Last
      Jedi.

PMID- 30099796
TI  - Systematic review of the effects of acute stress in binge eating disorder.
AB  - Binge eating disorder (BED) is characterized by recurrent episodes of eating an
      excessive amount of food over a discrete time period, while feeling a loss of
      control over one's eating. Although stress is one of the most commonly reported
      triggers of binge eating in individuals with BED, there has been little work
      examining the stress response specifically in individuals with the disorder. In
      this review, we examine what is known about how individuals with BED respond to
      acute stressors. A systematic literature search identified 14 relevant articles
      that report on the effects of experimentally induced stress on objective
      measures. Dependent measures that have been examined include changes in the
      levels of hormones such as cortisol and ghrelin, cardiovascular function, ad
      libitum food intake and eating rate. In this review, we describe the published
      findings and discuss their implications in the context of the wider literature.
      Overall, we found partial evidence that BED is associated with a heightened
      response to stress. Given the inconsistencies between studies, we suggest that
      reported differences between individuals with and without BED might be driven by
      factors that are correlated with, but not specific to, BED. We suggest that two
      priorities for this research area are to identify factors that modulate the
      stress response in individuals with BED, and to address the underrepresentation
      of males in this literature.

PMID- 30099797
TI  - What's Race Got to Do With It? Racial Socialization's Contribution to Black
      Adolescent Coping.
AB  - While youth generally experience stressors from developmental milestones, Black
      youth also face racialized stressors. Racial socialization has been found to help
      Black youth cope with racialized stressors, but research has yet to show its
      contribution to coping beyond general socialization practices. This study
      examines how racial socialization contributes beyond that of general coping
      socialization to coping behaviors. Fifty-eight third-eighth-grade (Mage  = 11.3,
      SD = 1.54) youth reported general coping socialization and racial socialization
      practices and coping behaviors. Results indicate that for engagement coping,
      racial socialization messages contributed significantly to parent-provided
      engaged socialization strategies. Implications are considered for the ways in
      which Black youth experience stress and require culturally specific practices for
      successful coping with frequently encountered stressors.

PMID- 30099799
TI  - A genetic portrait of the South-Eastern Carpathians based on autosomal short
      tandem repeats loci used in forensics.
AB  - OBJECTIVES: This work aimed to describe the genetic landscape of the Balkan
      Peninsula, as revealed by STR markers commonly used in forensics and spatial
      methods specifically developed for genetic data. METHODS: We generated and
      analyzed 16 short tandem repeats (STRs) autosomal genotypes in 287 subjects from
      ten administrative/geographical regions of Eastern Europe (Romania and the
      Republic of Moldova). We report estimates of the allele frequencies in these sub
      populations, their fixation indexes, and use these results to complement previous
      spatial analyses of Southern Europe. RESULTS: In seven out of ten analyzed
      regional samples the heterozygosity, averaged across loci, was lower than
      expected. The average Fis was 0.011. Among the 16 loci, five returned a
      significant fixation index Fst. The composite Fst across the 16 loci, among the
      10 regional samples, was 0.00417, a figure twice as large as that obtained with
      the same markers across the entire Northern Mediterranean. The first spatial
      principal component (sPC1) returned the picture of a Central-European pattern of
      frequencies for the Carpathians, which extended to the Southern boundary of the
      Balkan Peninsula. However, the 8 alleles extracted by sPC1 returned a picture of
      a strong reduction of the migration rate in the Carpathian region, mostly between
      the inner locations. CONCLUSIONS: Our results revealed an unexpected
      heterogeneity in the area. We believe that populations from some regions will
      require treatment as distinct entities when considered in forensic applications.

PMID- 30099798
TI  - Upregulation and release of soluble fms-like tyrosine kinase receptor 1 mediated
      by complement activation in human syncytiotrophoblast cells.
AB  - PROBLEM: Antiangiogenic molecule soluble fms-like tyrosine kinase receptor 1
      (sFLT1) released from trophoblast cells is associated with pregnancy-specific
      hypertensive disorder pre-eclampsia. Cause of elevated sFLT1 in pre-eclampsia
      patients is not well understood. Despite evidence of excess systemic and
      placental complement activation in pre-eclampsia patients, its role in
      pathophysiology is not clear. If the complement activation plays a role in
      upregulation and secretion of sFLT1 is not known. METHOD OF STUDY: Human
      trophoblast cells were isolated from term placentas and allowed to syncytialize.
      Complement was activated in vitro at sublethal levels on syncytiotrophoblast
      cells. Effect of complement activation on expression and release of sFLT1 was
      assessed by comparing its levels in these cells with and without complement
      activation. RESULTS: Sublethal level of complement activation on syncytialized
      human trophoblast cells induced upregulation of sFLT1 mRNA and protein.
      Complement also induced secretion of sFLT1 in a manner depending on degree of
      activation. Anaphylatoxins C3a induced upregulation but not the release of sFLT1.
      Release of terminal membrane attack complex (MAC) was associated with sFLT1
      secretion. CONCLUSION: Complement activation plays a major role in both the
      expression and secretion of sFLT1 from syncytial trophoblast cells. The terminal
      MAC complex is involved in its secretion. Increased levels of sFLT1 in pre
      eclampsia patients may be due to complement-induced upregulation and secretion.

PMID- 30099800
TI  - Body adiposity from childhood to adolescence in boys: Interaction with somatic
      maturity.
AB  - OBJECTIVES: To investigate the longitudinal relationship between adiposity and
      maturity status throughout the transition between childhood and adolescence in
      boys, and the moderation effect of maturation on adiposity trajectories. METHODS:
      This was a longitudinal study conducted with 197 boys who were followed over 3
      years (from childhood to adolescence). Body adiposity was estimated through the
      subcutaneous skinfold method, with measures of triceps and subscapular skinfolds.
      Skinfolds were analyzed singly and aggregated through the sum of skinfolds.
      Maturity status was estimated through Moore's method of estimated peak of height
      velocity, which uses an algorithm with stature and chronological age values and
      was categorized according to mean and SD. Analysis of covariance was used to test
      moderation effects. All analyses were conducted in STATA 14.0, at a 0.05 level of
      significance. RESULTS: Early maturing adolescents presented higher values of body
      adiposity at all moments when compared with on-time and late maturing adolescents
      (P < .05). Moreover, maturity status moderated the association between sum of
      skinfolds at childhood and sum of skinfolds at adolescence (F = 2.49; P = .045).
      CONCLUSION: Somatic maturation moderates the relationship between adiposity in
      childhood and adolescence, with earlier maturation associated with a greater
      increase in adiposity. Future tracking studies should consider the effects of
      maturity status when analyzing body adiposity.

PMID- 30099801
TI  - Redescription of a Hymenostome Ciliate, Tetrahymena setosa (Protozoa, Ciliophora)
      Notes on its Molecular Phylogeny.
AB  - In recent years, Tetrahymena species have been used as model organisms for
      research in a wide range of fields, highlighting the need for a fuller
      understanding of the taxonomy of this group. It is in this context that this
      paper uses living observation and silver staining methods to investigate the
      morphology and infraciliature of one Tetrahymena species, T. setosa (Schewiakoff
      1892 Verh. Naturh. Med. Ver. Heidelb., 4:544) McCoy (1975) Acta Protozool.,
      14:253; the senior subjective synonym of T. setifera Holz and Corliss (1956) J.
      Protozool., 3:112; isolated from a freshwater pond in Harbin, north-eastern
      China. This organism can be distinguished from other described Tetrahymena
      species mainly by its single caudal cilium, which is about twice the length of
      the somatic ciliature. While the Harbin isolate appears similar to the population
      described by Holz and Corliss (1956) J. Protozool., 3:112, an improved diagnosis
      for T. setosa is given based on the previous descriptions and the Harbin
      population. In summary, this species can be recognized mainly by the combination
      of the following characters: body in vivo approximately 40 MUm * 25 MUm, 21-26
      somatic kineties, one to four contractile vacuole pores associated with meridians
      6-11 and a single caudal cilium. The small subunit ribosomal (SSU) rRNA gene and
      the cox1 gene sequences of Harbin population are also characterized in order to
      corroborate that the isolated species branches in phylogenetic trees as a T.
      setosa species. The phylogenetic analysis also indicated that sequences of
      populations of Tetrahymena species should be published with detailed
      morphological identifications.

PMID- 30099802
TI  - Bilateral intraorbital masses in a child.

PMID- 30099803
TI  - Dopamine and opioids inhibit synaptic outputs of the main island of the
      intercalated neurons of the amygdala.
AB  - Neural circuits in the amygdala are important for associating the positive
      experience of drug taking with the coincident environmental cues. During
      abstinence, cue re-exposure activates the amygdala, increases dopamine release in
      the amygdala and stimulates relapse to drug use in an opioid dependent manner.
      Neural circuits in the amygdala and the learning that underlies these behaviours
      are inhibited by GABAergic synaptic inhibition. A specialised subtype of
      GABAergic neurons in the amygdala are the clusters of intercalated cells. We
      focussed on the main-island of intercalated cells because these neurons, located
      ventromedial to the basolateral amygdala, express very high levels of dopamine D1
      receptor and MU-opioid receptor, release enkephalin and are densely innervated by
      the ventral tegmental area. However, where these neurons project to was not fully
      described and their regulation by opioids and dopamine was incomplete. To address
      this issue we electrically stimulated in the main-island of the intercalated
      cells in rat brain slices and made patch-clamp recordings of GABAergic synaptics
      from amygdala neurons. We found that main-island neurons had a strong GABAergic
      inhibitory output to pyramidal neurons of the basolateral nucleus and the medial
      central nucleus, the major output zones of the amygdala. Opioids inhibited both
      these synaptic outputs of the intercalated neurons and thus would disinhibit
      these target zones. Additionally, dopamine acting at D1-receptors inhibited main
      island neuron synapses onto other main-island neurons. This data indicates that
      the inhibitory projections from the main-island neurons could influence multiple
      aspects of addiction and emotional processing in an opioid and dopamine dependent
      manner.

PMID- 30099804
TI  - The influences of genes, the environment, and social factors on the evolution of
      skin color diversity in India.
AB  - OBJECTIVES: Skin color is a highly visible and variable trait across human
      populations. It is not yet clear how evolutionary forces interact to generate
      phenotypic diversity. Here, we sought to unravel through an integrative framework
      the role played by three factors-demography and migration, sexual selection, and
      natural selection-in driving skin color diversity in India. METHODS: Skin
      reflectance data were collected from 10 diverse socio-cultural populations along
      the latitudinal expanse of India, including both sexes. We first looked at how
      skin color varies within and between these populations. Second, we compared
      patterns of sexual dimorphism in skin color. Third, we studied the influence of
      ultraviolet radiation on skin color throughout India. Finally, we attempted to
      disentangle the interactions between these factors in the context of available
      genetic data. RESULTS: We found that the relative importance of these forces
      varied between populations. Social factors and population structure have played a
      stronger role than natural selection in shaping skin color diversity across
      India. Phenotypic overprinting resulted from additional genetic mutations
      overriding the skin lightening effect of variants such as the SLC24A5 rs1426654-A
      allele in some populations, in the context of the variable influence of sexual
      selection. Furthermore, specific genotypes are not associated reliably with
      specific skin color phenotypes. This result has relevance for DNA forensics and
      ancient DNA research. CONCLUSIONS: India is a crucible of macro- and micro
      evolutionary forces, and the complex interactions of physical and social forces
      are visible in the patterns of skin color seen today in the country.

PMID- 30099805
TI  - Binge drinking is associated with attenuated frontal and parietal activation
      during successful response inhibition in fearful context.
AB  - Binge drinking is associated with increased impulsivity and altered emotional
      processing. This study investigated, in a group of university students who
      differed in their level of binge drinking, whether the ability to inhibit a pre
      potent response and to delay gratification is disrupted in the presence of
      emotional context. We further tested whether functional connectivity within
      intrinsic resting-state networks was associated with alcohol use. Higher
      incidence of binge drinking was associated with enhanced activation of the
      lateral occipital cortex, angular gyrus, the left frontal pole during successful
      response inhibition irrespective of emotional context. This observation suggests
      a compensatory mechanism. However, higher binge drinking attenuated frontal and
      parietal activation during successful response inhibition within a fearful
      context, indicating the selective emotional facilitation of inhibitory control.
      Similarly, higher binge drinking was associated with attenuated frontopolar
      activation when choosing a delayed reward over an immediate reward within the
      fearful, relative to the neutral, context. Resting-state functional data analysis
      revealed that binge drinking decreased coupling between the right supramarginal
      gyrus and Ventral Attention Network, indicating alcohol-associated disruption of
      functional connectivity within brain substrates directing attention. Together,
      our results suggest that binge drinking makes response inhibition more effortful,
      yet emotional (more arousing) contexts may mitigate this; disrupted functional
      connectivity between regions underlying adaptive attentional control, is a likely
      mechanism underlying these response inhibition effects associated with binge
      drinking.

PMID- 30099806
TI  - Longitudinal associations of android and gynoid fat mass on cardiovascular
      disease risk factors in normal weight and overweight boys during puberty.
AB  - OBJECTIVES: The aim of this longitudinal study was to assess associations between
      android and gynoid fat distribution and different cardiovascular disease risk
      factors in normal weight as well as overweight/obese boys during the pubertal
      period. METHODS: In total, 146 boys (baseline age 11.9 +/-0.6 years) were
      recruited for a 2-year longitudinal study. Total body fat percentage and android
      gynoid fat distribution were measured using DXA. In addition, waist and hip
      circumference was measured and body mass index (BMI) was calculated. Total
      cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL)
      cholesterol, triglycerides, insulin and glucose were measured, and homeostatic
      model assessment-insulin resistance (HOMA-IR) was calculated. Tanner stage and
      physical activity were assessed as covariates. RESULTS: Overweight subjects had
      worse values for most of the measured blood parameters (P <0.05). Higher android,
      gynoid fat mass (FM), and android/gynoid FM ratio were longitudinally associated
      with higher insulin and HOMA-IR values in both normal weight and overweight boys
      (P <0.05). In addition, higher android FM and gynoid FM were associated with
      worse values in HDL cholesterol, LDL cholesterol, and triglycerides in overweight
      boys (P <0.05). CONCLUSIONS: Our results suggest that higher android as well as
      gynoid fat have a strong impact on cardiovascular disease risk factors in both
      normal weight and overweight boys during the pubertal period. It can be suggested
      that measurement of fat distribution as android and gynoid fat is important for
      the assessment of the development or burden of metabolic diseases in boys with
      different weight statuses.

PMID- 30099807
TI  - Ecological sorting and character displacement contribute to the structure of
      communities of Clarkia species.
AB  - Despite long-standing interest in the evolutionary ecology of plants that share
      pollinators, few studies have explored how these interactions may affect
      communities during both community assembly (ecological sorting) and through
      ongoing, in situ evolution (character displacement), and how the effects of these
      interactions may change with community context. To determine if communities
      display patterns consistent with ecological sorting, we assessed the frequency of
      co-occurrence of four species of Clarkia in the southern Sierra foothills (Kern
      County, CA, USA). To investigate potential character displacement, we measured
      pollination-related traits on plants grown in a greenhouse common garden from
      seed collected in communities with one, two or four Clarkia species. Among the
      four species of Clarkia in this region, the two species that are often found in
      multi-species communities also co-occur with one another more frequently than
      expected under a null model. This pattern is consistent with ecological sorting,
      although further investigation is needed to determine the role of pollinators in
      shaping community assembly. Patterns of trait variation in a common garden
      suggest that these two species have diverged in floral traits and converged in
      flowering time where they co-occur, which is consistent with character
      displacement. Trait variation across community types also suggests that the
      process and outcome of character displacement may vary with community context.
      Because community context appears to affect both the direction and magnitude of
      character displacement, change in more species-rich communities may not be
      predictable from patterns of change in simpler communities.

PMID- 30099808
TI  - Cloning and Partial Characterization of a Cold Shock Domain-Containing Protein
      Gene from the Dinoflagellate Scrippsiella trochoidea.
AB  - CSPs, cold shock domain (CSD) containing proteins, are demonstrated to be
      involved in low temperature responses and various cellular processes under normal
      growth conditions. Here, we used the cosmopolitan, toxic, and resting cyst
      producing dinoflagellate Scrippsiella trochoidea as a representative harmful
      algal bloom-forming dinoflagellate to investigate the expression patterns of CSP
      in vegetative cells in response to temperature shocks and in resting cysts, with
      an objective to probe the possible function of CSP in dinoflagellates. The full
      length cDNA of a CSP gene from S. trochoidea (StCSP) was obtained which has a
      solely N-terminal CSD with conserved nucleic acids binding motifs. The qPCR
      results together indicated StCSP expression was not modulated by temperature at
      the transcriptional level and implied this gene may not be associated with
      temperature stress responses in S. trochoidea as the gene's name implies.
      However, we observed significantly higher StCSP transcripts in resting cysts
      (newly formed and maintained in dormancy for different periods of time) than that
      observed in vegetative cells (at exponential and stationary stages), indicating
      StCSP is actively expressed during dormancy of S. trochoidea. Taking together our
      recent transcriptomic work on S. trochoidea into consideration, we postulate that
      StCSP may play roles during encystment and cyst dormancy of the species.

PMID- 30099809
TI  - Four misunderstandings about cultural attraction.
AB  - Cultural attraction theory (CAT) is a research agenda the purpose of which is to
      develop causal explanations of cultural phenomena. CAT is also an evolutionary
      approach to culture, in the sense that it treats culture as a population of items
      of different types, with the frequency of tokens of those types changing over
      time. Now more than 20 years old, CAT has made many positive contributions,
      theoretical and empirical, to the naturalization of the social sciences. In
      consequence of this growing impact, CAT has, in recent years, been the subject of
      critical discussion. Here, we review and respond to these critiques. In so doing,
      we also provide a clear and concise introduction to CAT. We give clear
      characterizations of CAT's key theoretical notions, and we outline how these
      notions are derived from consideration of the natural character of cultural
      phenomena (Box ). This naturalistic quality distinguishes CAT from other
      evolutionary approaches to culture.

PMID- 30099810
TI  - Cytochemical Localization of Polyphenol Oxidase Activity in K2-Bodies of
      Saprolegnia ferax Secondary Zoospores.
AB  - Zoospores of the oomycete Saprolegnia ferax release adhesive material from K
      bodies at the onset of attachment to substrates. To understand more fully how K
      bodies function in adhesion, enzyme activity was investigated cytochemically in
      secondary zoospores. Presence of catalase, a marker enzyme for microbodies, was
      explored in the diaminobenzidine (DAB) reaction. Although pH 9.2 DAB-staining
      characteristic of catalase activity was detected in the granular matrix regions
      of K-bodies, reaction controls indicated that the reaction was due to oxidative
      enzyme activity other than catalase. Because polyphenol oxidase (PPO) is another
      metal-containing enzyme capable of oxidizing DAB, activity of this enzyme was
      tested with a more specific substrate, dihydroxyphenylalanine (DOPA). In the DOPA
      procedure, reaction product was exclusively localized within K-bodies, indicating
      the presence of PPO. Results with three methods of reaction controls (elimination
      of substrate, addition of a PPO enzyme inhibitor, and heat-inactivation of
      enzymes) all supported the presence of PPO in K-bodies. This study highlights
      potential roles for K-body PPO in stabilization of adhesion bodies by: cross
      linking matrix phenolic proteins or glycoproteins as K-bodies discharge adhesives
      onto substrates, or polymerizing phenolics protective against microbial attacks
      of the adhesion pad.

PMID- 30099811
TI  - Losartan ointment relieves hypertrophic scars and keloid: A pilot study.
AB  - Keloid and hypertrophic scars are two types of fibrosis caused by extracellular
      matrix overexpression, and angiotensin II via AT1 receptor is known to play a key
      role in stimulation of fibrosis. A pilot placebo controlled single blind study
      was carried out on patients with hypertrophic scars and keloids. A total of 37
      adult volunteers were randomly assigned into losartan 5% or placebo treatment
      groups. The treatment was performed twice a day for three months and a 6-month
      follow-up. The treatment was evaluated using Vancouver scar scale method.
      Totally, 30 participants were analyzed (Losartan ointment n = 20; placebo
      ointment n = 10; seven placebo volunteers left the study because they thought the
      treatment was not effective for them). In the losartan group, VSS scores dropped
      significantly (p < 0.01) both in keloid and hypertrophic scar patients.
      Vascularity and pliability were significantly reduced by losartan treatment (p <
      0.05). It can be concluded that losartan potassium ointment (5%) can alleviate
      the keloid and hypertrophic scar.

PMID- 30099812
TI  - Antibiotic therapy of diabetic foot infections: A systematic review of randomized
      controlled trials.
AB  - Diabetic foot infection is a common diabetic complication that may end in lower
      limb amputation if not treated properly. We performed this systematic review to
      assess the clinical efficacy of different antibiotic regimens, whether systemic
      or topical, in the treatment of moderate to severe diabetic foot infections. We
      searched Medline, Web of Science, SCOPUS, Cochrane CENTRAL, and ScienceDirect for
      randomized controlled trials that evaluated the efficacy of antibiotic regimens
      in moderate to severe diabetic foot infections. The primary outcome of interest
      was the clinical efficacy (cure/improvement rates) of the regimens. We included
      16 trials (4,158 patients) in this review, from which we extracted 10
      comparisons: some trials compared systemic antibiotics to each other, others
      compared systemic to topical agents, while one study compared the combined
      topical and systemic agents to systemic antibiotics alone. Qualitative analysis
      of the findings of these studies showed that: (1) pipracillin/tazobactam was
      superior to ertapenem in severe infections (clinical resolution rate: 91.5%
      compared with PIP/TAZ 97.2%, p <= 0.04), but had similar efficacy in moderate
      infections, (2) ertapenem was more effective than tigecycline in moderate to
      severe infections (absolute difference -5.5, [95% CI -11.0, 0.1]), (3) the
      adjuvant use of topical agents with systemic antibiotics improved the outcomes,
      compared with systemic antibiotics alone (p = 0.024), (4) the rates of recurrence
      and re-ulceration were significantly lower in patients using the amino-penicillin
      regimen, compared with those using oral/intravenous ofloxacin, and (5) lower
      rates of complications accompanied the imipenem/cilastatin regimen, compared with
      the pipracillin/tazobactam regimen (p = 0.13). In conclusion, data from the
      included studies showed better results for ertapenem when compared with
      tigecycline; however, it was inferior to pipracillin/tazobactam in severe
      infections. The adjuvant use of topical agents improves the efficacy of systemic
      antibiotics in diabetic foot infection.

PMID- 30099813
TI  - A computational method for semi-automatic measurement of pressure ulcers.
AB  - Pressure ulcers are skin lesions caused by the excessive compression of soft
      tissues between bones and hard surfaces that may increase treatment risks and
      costs. Manual techniques to evaluate the area of the affected region include the
      use of adhesive labels and rulers in direct contact with the ulcer. In this
      article, a semi-automatic method is proposed to estimate the lesion area through
      computerized techniques in different color spaces using filters and morphological
      operators. Experiments with a set of 110 images of pressure ulcers resulted in a
      statistically significant increase in effectiveness, when compared with other
      published results, reaching 90.8% of precision, 81.6% of sensitivity, and 81.3%
      of accuracy.

PMID- 30099815
TI  - Effects of self-regulatory skill usage on weight management behaviours: Mediating
      effects of induced self-efficacy changes in non-obese through morbidly obese
      women.
AB  - OBJECTIVES: Self-regulation is thought to play a role in overcoming barriers to
      weight management behaviour changes. This research assessed the extent that
      relationship is manifested through associated changes in self-efficacy, and
      effects based on degree of obesity. DESIGN: Data sets from three previous studies
      of the present research group were utilized. After assessment of change scores
      using repeated-measures ANOVA, mediation and moderation analyses assessed effects
      of changes in self-regulatory skill usage on changes in physical activity and
      fruit/vegetable intake through self-efficacy changes. Moderating effects of BMI
      were then assessed. METHODS: Women with body compositions ranging from non-obese
      (BMI < 30 kg/m2 ) to those with morbid obesity (BMI >= 40 kg/m2 ) were
      administered similar cognitive-behavioural treatments, and assessed on theory
      based psychosocial and behavioural measures over 6 months. RESULTS: From baseline
      to Month 6, changes in self-regulation for physical activity and eating, physical
      activity behaviours, fruit/vegetable intake, and self-efficacy for controlled
      eating were significant in non-obese women (n = 48) and women with Class 1 (n =
      43), Class 2 (n = 70), and Class 3 (n = 48) obesity. Positive effects were
      smaller in exercise self-efficacy. For each of the BMI-based groups, changes in
      self-efficacy significantly mediated the prediction of physical activity and
      fruit/vegetable intake by changes in self-regulation. In aggregated data, BMI
      significantly moderated the prediction of change in physical activity (higher BMI
      associated with a stronger association), but not fruit/vegetable intake, within
      those models. CONCLUSION: Increasing self-regulatory skills to overcome lifestyle
      barriers was found to be important for fostering improved weight loss behaviours,
      especially in the treatment of higher degrees of obesity in women. Statement of
      contribution What is already known on this subject? Self-efficacy is a malleable
      factor that predicts behaviour change within multiple theories. Learned self
      regulatory skills may effectively deal with lifestyle barriers associated with
      improvements in weight management behaviours. Increased physical activity and
      fruit/vegetable consumption predicts success with weight loss. What does this
      study add? Much of self-regulation's effect on physical activity and eating
      behaviours is through its impact on self-efficacy. Weight management treatments
      should emphasize self-regulatory skills development over simply health education.
      Effects of interrelations of self-regulation and self-efficacy are more effective
      as female weight increases.

PMID- 30099816
TI  - Excessive mortality and loss to follow-up among HIV-infected children in Guinea
      Bissau, West Africa: a retrospective follow-up study.
AB  - OBJECTIVES: To estimate the magnitude of mortality and loss to follow-up and
      describe predictors of mortality among HIV-infected children in Guinea-Bissau.
      METHODS: Retrospective follow-up study among HIV-infected children under 15 years
      of age at the largest HIV-clinic in Guinea-Bissau from 2006-2016. A multivariate
      Cox proportional hazards model was used to identify predictors of mortality.
      RESULTS: Of 525 children were included in the analysis: 371 (70.7%) with HIV-1,
      17 (3.2%) with HIV-2, 25 (4.8%) with HIV-1/2, and 112 (21.3%) with HIV of unknown
      type. At diagnosis, the median age was 3.5 years, 44.7% met the WHO criteria for
      severe immunodeficiency by age based on CD4 cell count, and 59.4% were
      underweight. The median follow-up time was 6 months. Despite the availability of
      antiretroviral treatment, the mortality rate was 10.4 deaths per 100 person-years
      of follow-up. Within the first year of follow-up, 11.0% died, 3.1% were
      transferred and 38.8% were lost to follow-up, leaving 47.1% in follow-up. Severe
      immunodeficiency (adjusted hazard ratio (aHR) = 2.52, 95% CI: 1.22-5.21) and
      underweight (aHR = 3.14, 95% CI: 1.40-7.02) were independent predictors of
      mortality. CONCLUSIONS: This study reveals a high rate of early mortality and
      loss to follow-up among HIV-infected children in Guinea-Bissau. Initiatives to
      improve patient retention are urgently needed.

PMID- 30099814
TI  - Targeting the FOXM1-regulated long noncoding RNA TUG1 in osteosarcoma.
AB  - Long noncoding RNAs (lncRNAs) play an important role in the proliferation and
      metastasis of osteosarcoma. Identification of the pathogenesis of osteosarcoma
      and development of new therapeutic strategies against osteosarcoma are urgently
      needed. In this study, we evaluated the expression of TUG1 (Taurine Upregulated
      Gene 1) in osteosarcoma tissues and selected it as our target for further
      analyses. In vitro, we found that TUG1 was upregulated by FOXM1 (Forkhead Box M1)
      in osteosarcoma cells. TUG1 accelerated osteosarcoma proliferation, migration,
      and invasion by competitively sponging miR-219a-5p, leading to upregulation of
      Phosphatidylinositol-4, 5-Bisphosphate 3-Kinase Catalytic Subunit Alpha and
      activation of the protein kinase B (AKT) signaling pathway. In addition, the AKT
      pathway activation promoted TUG1 expression by upregulating the expression of
      FOXM1, forming a positive feedback loop in osteosarcoma. Furthermore, we designed
      and synthesized therapeutic locked nucleic acids targeting TUG1. The
      proliferation of osteosarcoma was significantly repressed. Hence, TUG1 may be a
      potential biomarker and therapeutic target for osteosarcoma.

PMID- 30099817
TI  - Women's decision making about antidepressant use during pregnancy: A narrative
      review.
AB  - BACKGROUND: Depression is common, particularly among women of childbearing age,
      and can have far-reaching negative consequences if untreated. Efficacious
      treatments are available, but little is known about how women make depression
      treatment decisions during pregnancy. The purpose of this narrative review is to
      interpretively synthesize literature on women's decision making (DM) regarding
      antidepressant use during pregnancy. METHODS: The databases PubMed, CINAHL, and
      PsycINFO were searched between May 2015 and August 2017 for peer-reviewed,
      English-language papers using terms such as "depression," "pregnancy," and "DM."
      The literature matrix abstraction method was used to systematically abstract data
      from full articles that met criteria for inclusion. RESULTS: Of the articles
      abstracted (N = 10), half did not cite a DM theory on which the work was based.
      Key aspects of DM for this population were need for information and decision
      support, desire for active participation in DM, reflection on beliefs and values,
      evaluation of treatment option sequelae, and societal expectations. Treatment DM
      for depression during pregnancy is particularly impacted by the stigma associated
      with depression and societal expectations of pregnant women related to medication
      use during pregnancy. These findings, however, were based on studies of
      predominantly Caucasian and well-educated women. CONCLUSIONS: Women require a
      nonjudgmental environment, in which shared DM feels safe, to foster positive DM
      experiences and outcomes. Future research is needed to define how to best support
      women to make depression treatment decisions in pregnancy, with particular
      attention to DM in the second and third trimesters of pregnancy.

PMID- 30099819
TI  - Screening and follow-up for depression among Arab Americans.
AB  - BACKGROUND: The authors compared proportions and associations of depression
      screening, major depression, and follow-up care of Arab Americans compared to non
      Hispanic whites, non-Hispanic blacks, Asians, and Hispanics. METHODS:
      Administrative data was electronically abstracted from a large health system in
      metropolitan Detroit among 97,918 adult patients in 2014 and 2015. A valid and
      reliable surname list was used to identify Arab Americans. Using chi-squares, we
      examined the relationship between race/ethnicity and depression screening, major
      depression, and follow-up care. We calculated odds ratios (OR) and 95% confidence
      intervals (CI) to examine the relationship between the main independent variable
      of race/ethnicity and the dependent variables of depression screening and major
      depression while controlling for confounders. RESULTS: Arab American women were
      23% less likely to be screened for depression compared to non-Hispanic white
      women (OR = 0.77; 95% CI = 0.70, 0.86). The age- and sex-adjusted proportions of
      major depression were 5.5% for Arab Americans compared to 7.0% for Hispanics,
      6.0% for non-Hispanic blacks, 5.9% for non-Hispanic whites, and 1.5% for Asians.
      Arab Americans with major depression were less likely to follow up with a
      behavioral specialist and more likely to follow up with a primary care physician
      compared to other racial and ethnic groups. CONCLUSIONS: Our study adds to the
      discourse on depression care among Arab Americans by highlighting the existing
      disparities related to adequate screening and appropriate management of
      depression. Future studies should include information about the influences of
      acculturation, culture, stigma, family, and religion on depression care.

PMID- 30099818
TI  - Phase I dose-escalation trial of Sym004, an anti-EGFR antibody mixture, in
      Japanese patients with advanced solid tumors.
AB  - Sym004 is a 1:1 mixture of two antibodies targeting non-overlapping epitopes of
      the epidermal growth factor receptor that antagonizes ligand binding and induces
      receptor downregulation. In preclinical models, it has superior antitumor
      activity to cetuximab and panitumumab. Japanese adults aged >=20 years with an
      Eastern Cooperative Oncology Group status of 0/1 and life expectancy >=3 months
      were eligible. Patients in Part A (dose escalation) had refractory or recurrent
      late-stage solid tumors and received Sym004 6 mg/kg/wk (n = 3), 9 mg/kg loading/6
      mg/kg/wk (n = 6), 12 mg/kg/wk (n = 6), or 18 mg/kg biweekly (n = 6). Patients in
      expansion Part B (n = 30) had esophageal squamous cell carcinoma and received
      Sym004 at the dose recommended from Part A. Fifty-one patients received Sym004.
      No dose-limiting toxicities were observed in Part A. A dose of 12 mg/kg/wk was
      selected for Part B. All patients in Part B experienced treatment-related adverse
      events, most commonly dermatitis acneiform (76.7%). Eighteen grade >=3 treatment
      related adverse events and five serious adverse events occurred (cardiac arrest,
      lung infection, interstitial lung disease, toxic skin eruption, blood creatinine
      increase). Two patients had treatment-related adverse events resulting in death
      (cardiac arrest and blood creatinine increase). Five patients in Part B had a
      best overall response of partial response, 12 stable diseases and 12 disease
      progression (1 not evaluable). The objective response rate was 16.7% (95% CI:
      5.6%-34.7%). Sym004 therapy was well tolerated with no dose-limiting toxicities
      at any dose studied. Evidence of antitumor activity was seen in patients with
      esophageal squamous cell carcinoma. ClinicalTrials.gov Identifier: NCT01955473.

PMID- 30099821
TI  - Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at
      asymptomatic PSA progression in patients with metastatic castration-resistant
      prostate cancer.
AB  - OBJECTIVE: To evaluate the effects of switching from prednisone (P) to
      dexamethasone (D) at asymptomatic prostate-specific antigen (PSA) progression in
      patients with metastatic castration-resistant prostate cancer (mCRPC) treated
      with abiraterone acetate (AA). MATERIALS AND METHODS: Among 93 patients treated
      with AA between January 2013 and April 2016 in our institution, 48 consecutive
      asymptomatic patients with mCRPC, who experienced biochemical progression on
      treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5
      mg/day at PSA increase was administered until radiological and/or clinical
      progression. The primary endpoint was progression-free-survival (PFS). A
      prognostic score based on independent prognostic factors was defined. RESULTS:
      The median time to PSA progression on AA+P was 8.94 months. The median PFS on
      AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively.
      A total of 56.25% of patients showed a decrease or stabilization in PSA levels
      after the switch. In univariate analysis, three markers of switch efficiency were
      significantly associated with a longer PFS: long hormone-sensitivity duration
      (>=5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90%
      confidence interval [CI] 0.16-0.56); low PSA level at the time of switch (<50
      ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18-0.60); and short
      time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR
      0.41 (90% CI 0.21-0.81). In multivariate analysis, hormone sensitivity duration
      and PSA level were independent prognostic factors. CONCLUSION: A steroid switch
      from P to D appears to be a safe and non-expensive way of obtaining long-term
      responses to AA in selected patients with mCRPC. A longer PFS has been observed
      in patients with previous long hormone sensitivity duration, and/or low PSA level
      and/or short time to PSA progression on AA+P.

PMID- 30099820
TI  - Subthreshold PTSD and PTSD in a prospective-longitudinal cohort of military
      personnel: Potential targets for preventive interventions.
AB  - BACKGROUND: Prevention of PTSD requires identification of subpopulations
      contributing most to the population burden of PTSD. This study examines the
      relative contribution of subthreshold PTSD and probable PTSD on future PTSD in a
      representative military cohort. METHODS: We analyze data on 3,457 U.S. National
      Guard members from the state of Ohio, assessed by telephone annually from 2008 to
      2014. At each wave, participants were classified into one of three groups based
      on the PTSD Checklist: probable PTSD (DSM-IV-TR criteria), subthreshold PTSD
      (Criterion A1, at least one symptom in each cluster, symptom lasting longer than
      30 days, and functional impairment), and no PTSD. We calculated the exposure
      rate, risk ratio (RR), and population attributable fraction (PAF) to determine
      the burden of future probable PTSD attributable to subthreshold PTSD compared to
      probable PTSD. RESULTS: The annualized prevalence of subthreshold PTSD and
      probable PTSD was respectively 11.9 and 5.0%. The RR for probable PTSD was twice
      as great among respondents with probable PTSD the prior interview than that of
      those with subthreshold PTSD (7.0 vs. 3.4); however, the PAF was considerably
      greater in participants with subthreshold PTSD the prior interview (PAF = 35%;
      95% confidence interval (CI) = 26.0-42.9%) than in those with probable PTSD (PAF
      = 28.0%; 95% CI = 21.8-33.8%). Results were robust to changes in subthreshold
      PTSD definition. CONCLUSIONS: Subthreshold PTSD accounted for a substantial
      proportion of this population's future PTSD burden. Population-based preventive
      interventions, compared to an approach focused exclusively on cases of
      diagnosable PTSD, is likely to affect the greatest reduction in this population's
      future PTSD burden.

PMID- 30099822
TI  - MRI measurement of residual cervical length after radical trachelectomy for
      cervical cancer and the risk of adverse pregnancy outcomes: a blinded imaging
      analysis.
AB  - OBJECTIVE: To determine the association between the residual cervix measured on
      postoperative MRI after radical vaginal trachelectomy (RVT) and adverse
      obstetrical outcomes. DESIGN: Observational study. SETTING: Referral Cancer
      centre. POPULATION: Women who conceived after RVT for cervical cancer at the
      Royal Marsden Hospital, London, between 1995 and 2015. METHODS: Postoperative MRI
      scans were analysed by three researchers. The agreement between researchers was
      assessed by Pearson's correlation coefficient and Bland-Altman plot. Patients
      were divided into two groups (<10 and >=10 mm residual cervix) for the analysis
      of adverse obstetrical outcomes. MAIN OUTCOME MEASURES: Late miscarriage,
      premature delivery, premature rupture of membranes (PROM) and chorioamnionitis.
      RESULTS: Thirty-one MRI scans were available; 29 of these women had a pregnancy
      that progressed beyond the first trimester. There was a strong reproducibility of
      the measurement of residual cervix (P < 0.001). Nineteen women (65.5%) had <10 mm
      residual cervix and 10 (34.5%) had >=10 mm. Among women with <10 mm residual
      cervix, seven (36.8%) experienced PROM and ten (66.7%) had a preterm birth; No
      women with >=10 mm residual cervix had PROM and two (22.2%) had a preterm birth
      (P = 0.028 and P = 0.035, respectively). Overall, there were nine (16.7%) first
      trimester miscarriages, six (11.1%) late fetal losses, 12 (31.6%) preterm births
      and 36 (66.7%) live births. After a mean follow up of 78.1 months, 36 women were
      disease-free and one woman had died. CONCLUSIONS: MRI measurements of the
      residual cervix are reproducible between observers. The incidence of PROM and
      premature delivery is higher when the residual cervix after RVT is <10 mm.
      TWEETABLE ABSTRACT: The risk of prematurity after RVT can be predicted from
      measurements of residual cervical length on postoperative MRI scan.

PMID- 30099823
TI  - Descriptive epidemiology of salivary gland neoplasms in Nigeria: An AOPRC
      multicenter tertiary hospital study.
AB  - OBJECTIVES: Accurate diagnosis of salivary gland neoplasms (SGN) in many centers
      in Africa is limited by poor diagnostic resources and ancillary services. Hence,
      we have carried out a multicenter epidemiological study to understand the true
      burden of SGN in Nigeria. METHOD: In this descriptive cross-sectional study, we
      have deployed resources available to members of the African Oral Pathology
      Consortium (AOPRC) to examine the burden of salivary gland lesions in Nigeria,
      using a multicenter approach. Data from seven major tertiary health institutions
      in northern, western, and southern Nigeria were generated using a standardized
      data extraction format and analyzed using the Epi-info software (Version 7.0,
      Atlanta, USA). RESULT: Of the 497 cases examined across the seven centers, we
      observed that SGN occurred more in females than males. Overall, pleomorphic
      salivary adenoma (PA) was found to be the most common. PA was found to be the
      commonest benign SGN while adenocystic carcinoma (ADCC) was the commonest
      malignant SGN. Regional variations were observed for age group, diagnosis, and
      gender distribution. Significant statistical differences were found between males
      and females for malignant SGNs (p-value=0.037). CONCLUSION: We found regional
      variation in the pattern of distribution of SGN in Nigeria. This is the largest
      multicenter study of SGN in Nigeria, and our findings are robust and
      representative of the epidemiology of this neoplasm in Nigeria.

PMID- 30099824
TI  - Autonomous system for rapid field quantification of Escherichia coli in surface
      waters.
AB  - AIMS: The purpose of this work is to present and evaluate the performance of a
      novel Automatic Lab-in-vial Escherichia coli Remote Tracking technology based on
      an automated real-time defined substrate approach, implemented in both portable
      and in situ instruments. METHODS AND RESULTS: We present the fresh water
      calibration procedure, and assess performance using side-by-side comparison with
      most probable number (MPN) approaches in terms of accuracy, reproducibility and
      capability to correctly generate early-warning alerts. Long-term data from an
      operational in situ deployment at a potential bathing site is presented as well.
      CONCLUSIONS: Automatic Lab-in-vial Escherichia coli Remote Tracking technology is
      shown to be an accurate and rapid bacterial quantification technology, capable of
      autonomous in situ measurements with metrological capabilities comparable to
      those of an approved laboratory using MPN microplate techniques. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Rapid quantification of bacterial pollution is a requirement
      in water quality applications ranging from recreational water use, agriculture
      and aquaculture to drinking and wastewater treatment. The method and instruments
      presented in this work should enable fast and accurate bacterial concentration
      measurements to be performed in a portable or in situ manner, thus simplifying
      operational logistics, reducing time-to-result delays, and eliminating sample
      transportation constraints associated with traditional techniques.

PMID- 30099825
TI  - Visceral adiposity index as a predictor of NAFLD: A prospective study with 4-year
      follow-up.
AB  - BACKGROUND & AIMS: Although evidence indicates that visceral adipose tissue is
      associated with nonalcoholic fatty liver disease (NAFLD), it is unclear whether
      the visceral adiposity index (VAI) can predict the onset of NAFLD. This study
      aimed to determine whether the VAI is an independent risk factor of NAFLD and
      whether there is a dose-response relationship. METHODS: We explored the
      relationship between VAI levels and NAFLD in a health check-up cohort established
      in 2012. There were 4809 subjects with baseline data and results from 4 follow-up
      examinations. The diagnosis of NAFLD was established by demonstration of
      increased hepatic echogenicity with ultrasound and exclusion of alcohol
      overconsumption with questionnaires. We divided the subjects into 4 groups
      according to baseline VAI levels and used the Cox hazard regression model to
      estimate NAFLD risk by VAI quartile at baseline by adjusting for potential
      confounding factors. A Kaplan-Meier survival analysis was used to compare the
      risk of NAFLD incidence among individuals in each VAI quartile. RESULTS: The 4
      year cumulative incidence of NAFLD in this cohort was 13.9%. The hazard ratios
      (95% confidence intervals, 95% CI) for NAFLD in the second, third and fourth VAI
      quartiles compared with the first quartile were 1.42 (95% CI: 1.24-1.64), 1.73
      (95% CI: 1.51-1.99) and 2.13(95% CI: 1.86-2.45) respectively. The Kaplan-Meier
      survival analysis suggested that higher VAI levels predict higher incidences of
      NAFLD in a dose-dependent relationship. CONCLUSIONS: Our findings suggest that
      the VAI level is an independent risk factor of NAFLD and there is a dose-response
      relationship between VAI level and NAFLD risk.

PMID- 30099826
TI  - LncRNA HOXA11-AS drives cisplatin resistance of human LUAD cells via modulating
      miR-454-3p/Stat3.
AB  - Over the past several years, long non-coding RNAs (lncRNAs) have attracted more
      and more attention due to their special functions. They are vital biomarkers in
      multiple diseases. LncRNA HOMEOBOX A11 (HOXA11) has been found to be aberrantly
      expressed in some kinds of malignant tumors. In this study, we mainly discuss the
      oncogenic role of it in promoting malignant progression and chemoresistance in
      lung adenocarcinoma (LUAD) cells. The expression of HOXA11-AS was much stronger
      in cisplatin-resistant LUAD cells. Based on The Cancer Genome Atlas database,
      patients with high expression of HOXA11-AS had shorter survival time.
      Additionally, knockdown of HOXA11-AS caused positive changes in cell activities
      of LUAD. For example, cell proliferation and migration were weakened, the
      epithelial mesenchymal transition process was reversed, and apoptosis was
      induced. These changes were more obvious in cells treated with cisplatin. Next,
      the HOXA11-AS/miR-454-3p/Stat3 (signal transducer and activator of transcription
      3) pathway was found to influence the cisplatin resistance of LUAD cells. HOXA11
      AS specifically acted as a competing endogenous RNA (ceRNA) in LUAD cells. The
      combinations among these three genes were demonstrated. Finally, rescue assays
      were applied to demonstrate the ceRNA pattern consisting of HOXA11-AS, miR-454-3p
      and Stat3. In conclusion, lncRNA HOXA11-AS acted as a ceRNA to promote cisplatin
      resistance of human LUAD cells via the miR-454-3p/Stat3 axis.

PMID- 30099827
TI  - Fatty pancreas: A possible risk factor for pancreatic cancer in animals and
      humans.
AB  - Obesity, type 2 diabetes mellitus (T2DM) and aging are associated with pancreatic
      cancer risk, but the mechanisms of pancreatic cancer development caused by these
      factors are not clearly understood. Syrian golden hamsters are susceptible to N
      nitrosobis(2-oxopropyl)amine (BOP)-induced pancreatic carcinogenesis. Aging, BOP
      treatment and/or a high-fat diet cause severe and scattered fatty infiltration
      (FI) of the pancreas with abnormal adipokine production and promote pancreatic
      ductal adenocarcinoma (PDAC) development. The KK-Ay mouse, a T2DM model, also
      develops severe and scattered FI of the pancreas. Treatment with BOP induced
      significantly higher cell proliferation in the pancreatic ducts of KK-Ay mice,
      but not in those of ICR and C57BL/6J mice, both of which are characterized by an
      absence of scattered FI. Thus, we hypothesized that severely scattered FI may be
      involved in the susceptibility to PDAC development. Indeed, severe pancreatic FI,
      or fatty pancreas, is observed in humans and is associated with age, body mass
      index (BMI) and DM, which are risk factors for pancreatic cancer. We analyzed the
      degree of FI in the non-cancerous parts of PDAC and non-PDAC patients who had
      undergone pancreatoduodenectomy by histopathology and demonstrated that the
      degree of pancreatic FI in PDAC cases is significantly higher than that in non
      PDAC controls. Moreover, the association with PDAC is positive, even after
      adjusting for BMI and the prevalence of DM. Accumulating evidence suggests that
      pancreatic FI is involved in PDAC development in animals and humans, and further
      investigations to clarify the genetic and environmental factors that cause
      pancreatic FI are warranted.

PMID- 30099829
TI  - Glucocorticoid administration restores salience network activity in patients with
      spider phobia.
AB  - BACKGROUND: Glucocorticoids reduce phobic fear in patients with anxiety
      disorders. Although the neurobiology of anxiety disorders is not fully
      understood, convergent structural and functional neuroimaging studies have
      identified abnormalities in various brain regions, including those in the
      salience network (SN) and default mode network (DMN). Here, we examine the
      effects of glucocorticoid administration on SN and DMN activity during the
      processing of phobic stimuli. METHODS: We use functional magnetic resonance
      imaging to record brain activity in 24 female patients with spider phobia who
      were administered either 20 mg of cortisol or placebo while viewing pictures of
      spiders. Fourteen healthy female participants were tested with the same task but
      without substance administration. Independent component analysis (ICA) performed
      during stimulus encoding identified the SN and DMN as exhibiting synchronized
      activation in diverse brain regions; thus, we examined the effects of cortisol on
      these networks. Furthermore, participants had to rate their level of fear at
      various time points. RESULTS: Glucocorticoids reduced phobic fear in patients
      with spider phobia. The ICA performed during stimulus encoding revealed that
      activity in the SN and DMN was reduced in placebo-treated patients versus healthy
      controls. Brain activity in the SN, but not the DMN, was altered in cortisol-
      versus placebo-treated patients to a level that was similar to that observed in
      healthy controls. CONCLUSIONS: Activity in both the SN and DMN was reduced in
      patients with spider phobia. Cortisol administration altered the SN activity to a
      level that was comparable to that found in healthy controls. This alteration in
      SN activity might reflect the fear-reducing effects of glucocorticoids in phobia.

PMID- 30099831
TI  - Parents' and healthcare professionals' experiences of care after stillbirth in
      low- and middle-income countries: a systematic review and meta-summary.
AB  - BACKGROUND: Stillbirth has a profound impact on women, families, and healthcare
      workers. The burden is highest in low- and middle-income countries (LMICs). There
      is need for respectful and supportive care for women, partners, and families
      after bereavement. OBJECTIVE: To perform a qualitative meta-summary of parents'
      and healthcare professionals' experiences of care after stillbirth in LMICs.
      SEARCH STRATEGY: Search terms were formulated by identifying all synonyms,
      thesaurus terms, and variations for stillbirth. Databases searched were AMED,
      EMBASE, MEDLINE, PsychINFO, BNI, CINAHL. SELECTION CRITERIA: Qualitative,
      quantitative, and mixed method studies that addressed parents' or healthcare
      professionals' experience of care after stillbirth in LMICs. DATA COLLECTION AND
      ANALYSIS: Studies were screened, and data extracted in duplicate. Data were
      analysed using the Sandelowski meta-summary technique that calculates frequency
      and intensity effect sizes (FES/IES). MAIN RESULTS: In all, 118 full texts were
      screened, and 34 studies from 17 countries were included. FES range was 15-68%.
      Most studies had IES 1.5-4.5. Women experience a broad range of manifestations of
      grief following stillbirth, which may not be recognised by healthcare workers or
      in their communities. Lack of recognition exacerbates negative experiences of
      stigmatisation, blame, devaluation, and loss of social status. Adequately
      developed health systems, with trained and supported staff, are best equipped to
      provide the support and information that women want after stillbirth.
      CONCLUSIONS: Basic interventions could have an immediate impact on the
      experiences of women and their families after stillbirth. Examples include public
      education to reduce stigma, promoting the respectful maternity care agenda, and
      investigating stillbirth appropriately. TWEETABLE ABSTRACT: Reducing stigma,
      promoting respectful care and investigating stillbirth have a positive impact
      after stillbirth for women and families in LMICs.

PMID- 30099832
TI  - Pushing the limit: Resilience of an Arctic copepod to environmental fluctuations.
AB  - Life history strategies such as multiyear life cycles, resting stages, and
      capital breeding allow species to inhabit regions with extreme and fluctuating
      environmental conditions. One example is the zooplankton species Calanus
      hyperboreus, whose life history is considered an adaptation to the short and
      unpredictable growth season in the central Arctic Ocean. This copepod is commonly
      described as a true Arctic endemic; however, by statistically analyzing compiled
      observational data, we show that abundances are relatively low and later stages
      and adults dominate in the central Arctic Ocean basins, indicating expatriation.
      Combining data analyses with individual-based modeling and energy requirement
      estimation, we further demonstrate that while C. hyperboreus can reach higher
      abundances in areas with greater food availability outside the central Arctic
      basins, the species' resilience to environmental fluctuations enables the life
      cycle to be completed in the central Arctic basins. Specifically, the energy
      level required to reach the first overwintering stage-a prerequisite for
      successful local production-is likely met in some-but not all-years. This fine
      balance between success and failure indicates that C. hyperboreus functions as a
      peripheral population in the central Arctic basins and its abundance will likely
      increase in areas with improved growth conditions in response to climate change.
      By illustrating a key Arctic species' resilience to extreme and fluctuating
      environmental conditions, the results of this study have implications for
      projections of future biogeography and food web dynamics in the Arctic Ocean, a
      region experiencing rapid warming and sea ice loss.

PMID- 30099833
TI  - The new therapeutic choice of tranexamic acid solution in treatment of
      erythematotelangiectatic rosacea.
AB  - BACKGROUND: Erythematotelangiectatic rosasea is a common,chronic, relapsing
      disease characterized mainly by vascular components, for which many therapies may
      exist but with limited efficacy. OBJECTIVES: We decided to test the efficacy of
      tranexamic acid when applied topically on the affected areas.,Tranexamic acid is
      an antifibrinolytic,thus we considered it could be effective at this type of
      rosacea. METHODS: This is an unblinded study. We included 20 patients, having
      erythematotelangiectatic rosacea. All patients were women between 27 and 65 years
      old. We divided the patients in two groups,the first group was treated only with
      tranexamic acid solution (Transamin inj/sol 500 mg/5 mL) infused wet dressing for
      20 minutes, and the second group was treated with microneedling simultaneously
      with tranexamic acid solution topical application followed by tranexamic acid
      solution infused dressing therapy,every 15 days for four sessions. RESULTS: The
      improvement assecion was outlined according to the Investigator Global Assessment
      of Rosacea Severity Score (IGA-RSS) and the use of clinical photos and
      dermoscopy. All patients were improved in the end of the therapy. There was
      statistically significant improvement, 2 units IGA-RSS in the first group,
      whereas 3 units IGA-RSS in the second group. The improvement lasted more than
      four months. The tolerability of the use of tranexamic acid was also asessed.
      CONCLUSIONS: According to our results a new really promising simple, safe and
      cheap treatment option targeting mainly to the vascular net and the erythema of
      rosacea is proposed.

PMID- 30099830
TI  - Human immunodeficiency virus Tat-TIP30 interaction promotes metastasis by
      enhancing the nuclear translocation of Snail in lung cancer cell lines.
AB  - Lung cancer patients with human immunodeficiency virus (HIV) have a poorer
      prognosis than do patients without HIV infection. HIV1 Tat is a secreted viral
      protein that penetrates the plasma membrane and interacts with a number of
      proteins in non-HIV-infected cells. The loss of function of Tat-interacting
      protein 30 (TIP30) has been linked to metastasis in non-small cell lung cancer
      (NSCLC). However, it is unknown how the interaction of HIV1 Tat with TIP30
      regulates the metastasis of NSCLC cells. In this study, the overexpression of
      TIP30 decreased tumor growth factor-beta-induced epithelial-to-mesenchymal
      transition (EMT) and invasion of NSCLC cells, whereas the knockdown of TIP30
      promoted EMT, invasion and stemness. Exposure to recombinant HIV1 Tat proteins
      promoted EMT and invasion. A mechanistic study showed that the interaction of
      HIV1 Tat with TIP30 blocked the binding of TIP30 to importin-beta, which is
      required for the nuclear translocation of Snail. Indeed, the loss of TIP30
      promoted the nuclear translocation of Snail. In vivo studies demonstrated that
      the overexpression of TIP30 inhibited the metastasis of NSCLC cells. In contrast,
      the coexpression of HIV1 Tat and TIP30 diminished the inhibitory effect of TIP30
      on metastasis. Immunohistochemistry confirmed that TIP30 overexpression reduced
      the nuclear localization of Snail, whereas the coexpression of HIV1 Tat and TIP30
      increased nuclear Snail in metastatic tumors. In conclusion, the binding of HIV1
      Tat to TIP30 enhanced EMT and metastasis by regulating the nuclear translocation
      of Snail. Targeting Tat-interacting proteins may be a potential therapeutic
      strategy to prevent metastasis in NSCLC patients with HIV infection.

PMID- 30099834
TI  - Is mentalization-based therapy effective in treating the symptoms of borderline
      personality disorder? A systematic review.
AB  - OBJECTIVE: This review sought to systematically review evidence on the efficacy
      of mentalization-based therapy (MBT) for the treatment of borderline personality
      disorder (BPD), in particular, in decreasing psychiatric symptoms associated with
      BPD and its comorbid disorders. METHOD: Fourteen papers were included in the
      review which examined the effectiveness of MBT in the context of BPD; these
      included 11 original studies and three follow-up papers. RESULTS: Mentalization
      based therapy was found to achieve either superior or equal reductions in
      psychiatric symptoms when compared with other treatments (supportive group
      therapy, treatment as usual/standard psychiatric care, structured clinical
      management, and specialized clinical management). DISCUSSION: Mentalization-based
      therapy can achieve significant reductions in BPD symptom severity and the
      severity of comorbid disorders as well as increase quality of life. However,
      caution is required, as the need for better quality research such as randomized
      controlled trials is pressing. Research is also needed on the proposed mediators
      of MBT. PRACTITIONER POINTS: Mentalization-based therapy (MBT) is increasingly
      being considered as a treatment for people with borderline personality disorder
      (BPD), and a systematic review was required to investigate its effectiveness. MBT
      was found to be equally as effective or superior to well-established comparison
      treatments of BPD, however, the majority of studies was of unsatisfying quality.
      Little is known about the mechanisms of MBT. Further, better quality trials are
      needed to investigate its efficacy in treating BPD.

PMID- 30099835
TI  - Editorial Decisions: Does Reject Really Mean Resubmit and Other Frequently Asked
      Questions.

PMID- 30099836
TI  - Energy-dependent OAR sparing and dose conformity for total marrow irradiation of
      obese patients.
AB  - PURPOSE: To investigate the effect on target coverage and organs at risk sparing
      by using 10 versus 6 MV for VMAT total marrow irradiation of obese patients.
      METHODS AND MATERIALS: Twenty-six total marrow irradiation, TMI, treatment plans
      delivered between December 2014 and June 2017 were reviewed and 10 were chosen
      for replanning based on patient characteristics and plan metrics. Beam geometry
      and isocenter placement were conserved, energy was changed from 6 to 10 MV and
      plans were reoptimized. Resulting dose distributions were compared to original
      plans to evaluate any potential advantage of choosing one energy over the other.
      RESULTS: Target coverage and total monitor units were consistent between the 6
      and 10 MV plans when averaged over all ten patients. Improvement in the
      conformity index (-11.0%, P = 0.009) when using 10 MV was statistically
      significant compared to the 6 MV plans. Volumes of normal tissue receiving 50%,
      75%, and 90% Rx all decreased for the 10 MV plans compared to the original 6 MV
      plans. The mean dose to individual OARs decreased significantly for all
      investigated structures except for the lenses, oral cavity, and genitalia. The
      largest decreases in Dmean were found for the rectum (22.4%, P = 0.004) and
      bladder (18.1%, P = 0.005). The three highest priorities for sparing during plan
      optimization (lungs, liver, and heart), showed decreases of 7.6%, 16.1%, and
      13.0%. CONCLUSIONS: Use of a higher energy 10 MV beam provided similar dose to
      target while achieving increased OAR and normal tissue sparing for the patients
      reviewed in this study.

PMID- 30099837
TI  - Adolescent parenthood associated with adverse socio-economic outcomes at age 30
      years in women and men of the Pelotas, Brazil: 1982 Birth Cohort Study.
AB  - OBJECTIVE: To investigate the potential long-term effects of adolescent
      parenthood on completed education and income. DESIGN: Population-based birth
      cohort study. SETTING: All live births in 1982, whose mothers lived in the urban
      area of Pelotas, southern Brazil. SAMPLE: A total of 3701 participants: 1914
      women and 1787 men at age 30 years. METHODS: Questionnaires were completed by the
      mothers in the early phases of this study, and by the cohort members in
      adolescence and adulthood. Linear regression models and G-computation were used
      in the analyses. MAIN OUTCOME MEASURES: Educational attainment and income at age
      30 years. RESULTS: In women, adolescent parenthood was associated with lower
      attained education compared with women without adolescent maternity: by -2.8
      years [95% confidence interval (CI) -3.2 to -2.3] if their first birth was at age
      16-19, and by -4.4 years (-5.5 to -3.3) at age 11-15. These effects were greater
      among women who had three or more children. Women with adolescent parenthood also
      had 49 or 33% lower income at age 30 if their first child was born when aged 16
      19 or 11-15, respectively. In men, the adverse effect of adolescent parenthood on
      education appeared to be mediated by a higher number of children and there was no
      effect of adolescent paternity on income at age 30 years. CONCLUSION: These
      findings suggest lasting socio-economic disadvantages of adolescent parenthood,
      with larger effects being apparent in women than in men. TWEETABLE ABSTRACT:
      Adolescent parenthood has an adverse effect on educational attainment later in
      life, and on household income among women.

PMID- 30099839
TI  - The use of platelets in regenerative medicine and proposal for a new
      classification system: guidance from the SSC of the ISTH.
AB  - Autologous and single-donor allogenic platelet preparations are increasingly
      being used in many areas of regenerative medicine. However, there are few
      properly controlled randomized clinical trials, and the preparation, content and
      characteristics of platelet preparations are generally poorly defined and
      controlled. The Platelet Physiology Subcommittee of the Scientific and
      Standardization Committee (SSC) of the ISTH formed a working party of experts
      with the aim of producing consensus recommendations for guidance on the use of
      platelets in regenerative medicine. Owing to a lack of investigations that
      provide definitive evidence for the efficacy, definition and use of different
      platelet preparations in regenerative medicine, there were insufficient data to
      develop evidence-based guidelines. Therefore, the RAND method was used, which
      obtains a formal consensus among experts particularly when scientific evidence is
      absent, scarce and/or heterogeneous. Using this approach, each expert scored as
      'appropriate', 'uncertain' or 'inappropriate' a series of 45 statements about the
      practice of regenerative medicine with platelets, which included different
      sections on general aspects, platelet preparations, clinical trial design, and
      potential utility in different clinical scenarios. After presentation and public
      discussion at SSC meetings, the assessments were further refined to produce final
      consensus recommendations, which constitute the subject of the present report.

PMID- 30099838
TI  - A quantitative assessment of the consequences of allowing dose heterogeneity in
      prostate radiation therapy planning.
AB  - Target dose uniformity has been historically an aim of volumetric modulated arc
      therapy (VMAT) planning. However, for some sites, this may not be strictly
      necessary and removing this constraint could theoretically improve organ-at-risk
      (OAR) sparing and tumor control probability (TCP). This study systematically
      investigates the consequences of PTV dose uniformity that results from the
      application or removal of an upper dose constraint (UDC) in the inverse planning
      process for prostate VMAT treatments. OAR sparing, target coverage, hotspots, and
      plan complexity were compared between prostate VMAT plans with and without the
      PTV UDC optimized using the progressive resolution optimizer (PRO, Varian Medical
      Systems, Palo Alto, CA). Removing the PTV UDC, the median D1cc reached 144.6% for
      the CTV and the PTV, and an average increase of 3.2% TCP was demonstrated, while
      CTV and PTV coverage evaluated by D99% was decreased by less than 0.6% with
      statistical significance. Moreover, systematic improvement in the rectum dose
      volume histograms was shown (a 5-10% decrease in the volume receiving 50% to 75%
      prescribed dose), resulting in an average decrease of 1.3% (P < 0.01) in the
      rectum normal tissue complication probability. Additional consequences included
      potentially increased dose to the urethra as evaluated by PTV D0.035cc (median:
      153.4%), delivering 283 extra monitor units (MUs), and slightly higher degrees of
      modulation. In general, the results were consistent when a different optimizer
      (Photon Optimizer, Varian Medical Systems) was used. In conclusion, removing the
      PTV UDC is acceptable for localized prostate cases given the systematic
      improvement of rectal dose and TCP. It can be particularly useful for cases that
      do not meet the rectum dose constraints with the PTV UDC on. This comes with the
      foreseeable consequences of increased dose heterogeneity in the PTV and an
      increase in MUs and plan complexity. It also has a higher requirement for
      reproducing the position and size of the target and OARs during treatment.
      Finally, with the PTV UDC completely removed, in some cases the maximum doses
      within the PTV did approach levels that may be of concern for urethral toxicity
      and therefore in clinical implementation it may still be necessary to include a
      PTV UDC, but one based on limiting toxicity rather than enforcing dose
      homogeneity.

PMID- 30099840
TI  - ADAMTS-13 activity and ischemic heart disease: a Mendelian randomization study.
AB  - : Essentials Cardiovascular disease remains the leading cause of global mortality
      despite progress in control. We assessed the role of ADAMTS-13 in ischemic heart
      disease using Mendelian randomization. Genetically instrumented ADAMTS-13
      activity reduced ischemic heart disease. Therapeutics targeting ADAMTS-13
      activity could perhaps be repurposed in ischemic heart disease. BACKGROUND:
      Despite great progress in the prevention and control of cardiovascular disease,
      it remains the leading cause of global mortality and morbidity, with new
      unexpected risk factors emerging and few effective new pharmaceutical treatments.
      ADAMTS-13 is involved in a clotting disorder, thrombotic thrombocytopenic
      purpura, for which new treatments are being developed. Observationally, ADAMTS-13
      activity is inversely associated with ischemic heart disease (IHD) but positively
      associated with diabetes. OBJECTIVES: To obtain unconfounded estimates of the
      effect of ADAMTS-13 on IHD, diabetes and lipids. METHODS: We applied genetic
      variants strongly, (P < 5 * 10-8 ), solely and independently associated with
      ADAMTS-13 to the largest available extensively genotyped case-control studies of
      IHD and diabetes and to a large study of lipids to obtain Mendelian randomization
      inverse variance weighted (IVW) estimates. Sensitivity was evaluated through
      weighted median and MR-Egger estimates. RESULTS: Genetically predicted ADAMTS-13
      activity, based on three genetic variants, was consistently inversely associated
      with IHD (IVW odds ratio [OR] 0.91 per effect size; 95% confidence interval [CI]
      0.86-0.97) but not with diabetes (OR 0.94, 95% CI 0.88-1.01) or high or low
      density lipoprotein cholesterol (0.01, 95% CI -0.02 to 0.04; -0.01, 95% CI -0.04
      to 0.02, respectively). ADAMTS-13 antigen, based on four genetic variants, was
      not associated with any outcome. CONCLUSIONS: This genetic validation of ADAMTS
      13 activity as a target of intervention in IHD raises the possibility of new ways
      of prevention and treatment being developed by repurposing therapeutics that
      raise ADAMTS-13 activity, or by other environmental or dietary interventions that
      raise ADAMTS-13 activity.

PMID- 30099841
TI  - A scoping review on the prevalence of Shiga-toxigenic Escherichia coli in wild
      animal species.
AB  - Zoonotic pathogens constitute the major source (60.3%) of emerging infectious
      diseases. Previous studies have investigated the prevalence of Shiga-toxigenic
      Escherichia coli (STEC) among wild animal species, but comprehensive data are
      needed to assess the role that these animals have in the transmission of STEC
      infections to the human population via faecal contamination of the environment,
      agri-food or water chain. Due to the nature of these microorganisms in which this
      human-animal-environment interface plays a relevant role on the disease's
      dynamics, a "One Health" approach is needed to prevent and control the worldwide
      spread. The aim of this study was to review the published research on the
      prevalence of STEC in wildlife. The search was performed using several online
      databases consisting of three blocks of specific search terms covering pathogen,
      type of study and population. Two reviewers applied the inclusion and exclusion
      criteria to screening and eligibility phases. Two hundred and twenty-five
      abstracts were screened for relevance, and 72 were included for data analysis.
      Most studies (77.8%) investigated the prevalence of STEC in ruminants and urban
      birds. Their role in transmitting the pathogen to humans, other animals and the
      agri-food chain is potentiated by the peculiar biological characteristics in
      ruminants and improved adaptation of urban birds to urban environments. The
      popularity of convenience and voluntary response sampling may be due to the lack
      of human-made boundaries on the wild animal species' habitat and having some
      samples from hunted-harvested animals. To our knowledge, this is the first
      comprehensive review on STEC prevalence in wild animal species from studies
      conducted across the globe. We recommend that future research includes and
      compares samples from varying origins (i.e., human, animal, environment and food)
      and applies a "One Health" approach to the emerging challenges that STEC poses to
      public health.

PMID- 30099842
TI  - Unusual sequelae of a subluxated primary incisor on its permanent successor
      tooth.
AB  - Traumatic dental injuries (TDIs) such as subluxations of primary teeth can have
      significant consequences on their developing successors. The purpose of this
      report is to present a 3-year-old boy who encountered subluxation injuries to his
      primary incisors which subsequently had an unusual consequence on the permanent
      successor. On the day of the TDI, based on clinical and radiographic
      examinations, a diagnosis of subluxation of teeth 52, 51 and 61 was made. By age
      5, the patient reported that tooth 51 had exfoliated, and consequently, tooth 11
      had erupted into the oral cavity, but it was very loose. Eventually, the patient
      lost the crown of tooth 11 during his routine daily activities. Furthermore,
      radiographic examination at age 11 revealed a small root-like structure in the
      tooth 11 region. It is very unusual to have premature loss of a permanent incisor
      following subluxation to its predecessor. Therefore, the present case serves as a
      good example to emphasize that even minor TDIs are of considerable importance as
      they may lead to unexpected consequences.

PMID- 30099843
TI  - Heparin-induced thrombocytopenia-associated thrombosis: from arterial to venous
      to venous limb gangrene.
AB  - Heparin-induced thrombocytopenia (HIT) is an acquired immune-mediated
      hypercoagulability state that is strongly associated with thrombosis. During the
      1970s and 1980s, the prevailing concept was that HIT was associated only with
      arterial thrombosis, through its unique pathogenesis via heparin-dependent,
      platelet-activating IgG antibodies. However, in 1990, when I began to encounter
      HIT in my clinical practice, I found that most such patients developed
      symptomatic venous thrombosis. This historical sketch summarizes some of the
      research that challenged the dogma of HIT being a mainly arterial prothrombotic
      disorder. Two studies - one a substudy of a randomized trial of post-orthopedic
      surgery thromboprophylaxis, and the second a retrospective five-hospital analysis
      of consecutive patients with positive test results for HIT antibodies - showed a
      marked predominance of venous over arterial thrombosis complicating HIT (~ 4 :
      1). By the end of the 1990s, an even more dramatic manifestation of HIT
      associated venous thrombosis was recognized: venous limb gangrene. Here, ischemic
      limb necrosis occurs despite palpable arterial pulses, as a result of both
      macrovascular and microvascular venous thrombosis. The surprising explanation was
      natural anticoagulant impairment (severe depletion of protein C, a vitamin K
      dependent anticoagulant) resulting from treatment of HIT-associated deep vein
      thrombosis with warfarin (vitamin K antagonist). These insights from HIT research
      helped to elucidate the pathogenesis of ischemic limb losses in other intense non
      HIT hypercoagulability states, including warfarin-associated venous limb gangrene
      complicating cancer-associated hypercoagulability, and symmetrical peripheral
      gangrene complicating disseminated intravascular coagulation of critical illness,
      in which proximate 'shock liver' helps to explain the profound failure of natural
      anticoagulant systems (protein C; antithrombin) in predisposing to peripheral
      limb microthrombosis in circulatory shock.

PMID- 30099844
TI  - Healthcare utilization in chronic thromboembolic pulmonary hypertension after
      acute pulmonary embolism.
AB  - Essentials Diagnostic delay of chronic thromboembolic pulmonary hypertension
      (CTEPH) is long. We explored healthcare utilisation of patients diagnosed with
      CTEPH after pulmonary embolism. A large number of physicians were consulted and
      test results were not always interpreted correctly. Better education and higher
      awareness of CTEPH may lead to faster diagnosis. SUMMARY: Background The median
      diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) is 14
      months, which may affect prognosis. We aimed to explore the healthcare
      utilization of patients diagnosed with CTEPH after acute pulmonary embolism (PE),
      and to identify the causes of diagnostic delay. Methods We collected all data on
      patient symptoms, medical specialist referrals and ordered diagnostic tests to
      reconstruct the clinical pathways of 40 patients referred to the VU University
      Medical Center Amsterdam (VUMC, the Netherlands) for CTEPH treatment. Diagnostic
      delay was defined as the time between first symptom onset and referral to the
      VUMC. Correlations of patient-specific characteristics and diagnostic delay were
      evaluated. Results Patients consulted four (median) different physicians for a
      median of 13 (interquartile range [IQR] 10-18) consultations before the correct
      diagnosis was made. The median diagnostic delay was 21 months (IQR 12-49 months).
      Echocardiographic results suggestive of CTEPH were not always followed by an
      adequate work-up; most patients were not subjected to ventilation/perfusion
      scanning. Prior cardiopulmonary comorbidity and recurrent venous thromboembolism
      were predictors of a longer delay. Conclusion Healthcare utilization in patients
      before their final CTEPH diagnosis was far from optimal, contributing to a
      considerable diagnostic delay. Better education and higher awareness of CTEPH
      among PE caretakers may lead to faster diagnosis.

PMID- 30099845
TI  - Glucagon-like peptide-1 receptor agonists for type 2 diabetes: A rational drug
      development.
AB  - Today, glucagon-like peptide-1 (GLP-1) receptor agonists are established glucose
      lowering drugs used in the management of type 2 diabetes. Their development
      emerged from the understanding that a combined islet dysfunction comprising of
      impaired insulin secretion and exaggerated glucagon secretion is the key defect
      of hyperglycemia. GLP-1 was shown to target these defects, and after the
      discovery that dipeptidyl peptidase-4 inactivates native GLP-1, several different
      dipeptidyl peptidase-4-resistant GLP-1 receptor agonists have been developed.
      They are administered subcutaneously, but show differences in molecular
      structure, molecular size and pharmacokinetics, the latter allowing twice-daily,
      once-daily or once-weekly administration. They have been shown to be efficient in
      reducing both glycated hemoglobin and bodyweight, and to be safe and highly
      tolerable. Cardiovascular outcomes trials have shown them to be neutral or
      beneficial. GLP-1 receptor agonists are positioned as add-ons to metformin alone
      or in combination with oral agents in the clinical paradigm. They are also
      efficient when combined with insulin, and fixed dose combinations with long
      acting insulin have been developed. Recent development includes a very long
      administration schedule and oral availability. The research from the first
      demonstration of the antidiabetic action of GLP-1 in the early 1990s to the
      enormously accumulated data today represents a successful and rational
      development, which has been characterized by focused perseverance to establish
      this therapy in the management of type 2 diabetes.

PMID- 30099846
TI  - GlaR (YugA)-a novel RpiR-family transcription activator of the Leloir pathway of
      galactose utilization in Lactococcus lactis IL1403.
AB  - Bacteria can utilize diverse sugars as carbon and energy source, but the
      regulatory mechanisms directing the choice of the preferred substrate are often
      poorly understood. Here, we analyzed the role of the YugA protein (now designated
      GlaR-Galactose-lactose operon Regulatory protein) of the RpiR family as a
      transcriptional activator of galactose (gal genes) and lactose (lac genes)
      utilization genes in Lactococcus lactis IL1403. In this bacterium, gal genes
      forming the Leloir operon are combined with lac genes in a single so-called gal
      lac operon. The first gene of this operon is the lacS gene encoding galactose
      permease. The glaR gene encoding GlaR lies directly upstream of the gal-lac gene
      cluster and is transcribed in the same direction. This genetic layout and the
      presence of glaR homologues in the closest neighborhood to the Leloir or gal-lac
      operons are highly conserved only among Lactococcus species. Deletion of glaR
      disabled galactose utilization and abrogated or decreased expression of the gal
      lac genes. The GlaR-dependent regulation of the gal-lac operon depends on its
      specific binding to a DNA region upstream of the lacS gene activating lacS
      expression and increasing the expression of the operon genes localized
      downstream. Notably, expression of lacS-downstream genes, namely galMKTE, thgA
      and lacZ, is partially independent of the GlaR-driven activation likely due to
      the presence of additional promoters. The glaR transcription itself is not
      subject to catabolite control protein A (CcpA) carbon catabolite repression (CRR)
      and is induced by galactose. Up to date, no similar mechanism has been reported
      in other lactic acid bacteria species. These results reveal a novel regulatory
      protein and shed new light on the regulation of carbohydrate catabolism in L.
      lactis IL1403, and by similarity, probably also in other lactococci.

PMID- 30099847
TI  - Safety and tolerability of empagliflozin in East Asian patients with type 2
      diabetes: Pooled analysis of phase I-III clinical trials.
AB  - AIMS/INTRODUCTION: We investigated the safety and tolerability of empagliflozin
      (EMPA) in East Asian patients with type 2 diabetes. MATERIALS AND METHODS: Data
      were pooled from participants with type 2 diabetes evenly randomized to a
      placebo, EMPA 10 mg or EMPA 25 mg in 15 phase I-III trials. Adverse events (AEs)
      were analyzed in the subgroup of trial participants from East Asian
      countries/regions. RESULTS: In total, 709, 724 and 708 East Asian trial
      participants with type 2 diabetes received a placebo, EMPA 10 mg and EMPA 25 mg,
      respectively; total exposure was 953, 1,072, and 1,033 patient-years in these
      groups, respectively. The EMPA and placebo groups had similar incidences of
      severe AEs, serious AEs and AEs leading to discontinuation. Incidences of
      hypoglycemia differed according to anti-diabetes medication used at baseline.
      Higher rates of events consistent with genital infection were observed with EMPA
      (EMPA 1.5-1.7/100, placebo 0.2/100 patient-years). Rates of AEs consistent with
      volume depletion were comparable among treatment groups (0.8-1.4/100 patient
      years), but in trial participants aged >=65 years, the rate was greater with EMPA
      25 mg (EMPA 25 mg 3.5/100, placebo 2.0/100 patient-years). Incidences of events
      consistent with urinary tract infection, thromboembolic events, renal events,
      hepatic AEs, diabetic ketoacidosis, fractures and lower limb amputation were
      similar between EMPA and the placebo. CONCLUSIONS: In the present pooled
      analysis, EMPA was well tolerated in East Asian type 2 diabetes patients based on
      >2,100 patient-years' exposure, consistent with results from the overall analysis
      population.

PMID- 30099848
TI  - Progranulin is a novel biomarker for predicting an acute exacerbation of chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Progranulin is a pleiotropic glycosylated protein precursor that
      plays an important role in inflammation. Limited data exist regarding the role of
      progranulin in the acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD). OBJECTIVES: The study is to assess the efficiency of progranulin as a
      circulating biomarker of AECOPD. METHODS: The plasma progranulin levels were
      measured and compared in patients with AECOPD (n = 52), patients with stable COPD
      (n = 56), and healthy controls (n = 36). In patients with AECOPD, plasma
      progranulin levels were measured repeatedly on the last day of hospitalization.
      Demographical data, pulmonary function, and laboratory parameters were recorded.
      RESULTS: Patients with AECOPD had higher plasma progranulin levels than both
      stable COPD patients and healthy controls (158.77 +/- 48.17, 109.00 +/- 25.05,
      93.67 +/- 14.71 ng/mL, respectively; P < .001). In patients with AECOPD, the
      plasma progranulin levels significantly decreased on the last day of
      hospitalization compared with those on the first day of hospitalization (138.51
      +/- 44.68 vs. 158.77 +/- 48.17 ng/mL, P = .042). The progranulin levels were
      negatively correlated to FEV1%pred but positively correlated to neutrophil-to
      lymphocyte ratio and C-reactive protein in all patients with COPD. Multivariate
      logistic regression and ROC analysis revealed progranulin (odds ratio 1.05, 95%
      confidence interval 1.03-1.08, P < .001) as an independent predictor of AECOPD,
      with an area under the curve of 0.82. CONCLUSIONS: Progranulin may be a valuable
      blood biomarker of AECOPD and progranulin may be involved in the pathogenesis of
      AECOPD by disturbing inflammatory responses.

PMID- 30099849
TI  - Assessing rabies knowledge gaps in human and animal healthcare professionals
      practicing in Washington, DC-A one health approach.
AB  - Once a person is exposed to the rabies virus, it is universally fatal unless
      postexposure prophylaxis (PEP) is administered promptly. In the United States,
      determining whether PEP recommeded is often a collaborative effort where health
      departments work with both animal and human healthcare professionals to enact
      animal quarantines (or rabies testing), recommending PEP when appropriate. A
      failure in the knowledge base of either profession can result in incorrect PEP
      recommendations and an increased risk of adverse outcomes. To assess rabies
      knowledge in licensed physicians and veterinarians practicing in Washington, DC,
      we conducted a survey from December 2, 2016, to January 2, 2017, assessing their
      knowledge of the clinical signs, epidemiology and the primary vectors of rabies.
      These responses were compared between the two groups. Physician-specific or
      veterinary-specific questions regarding the correct PEP schedule and
      administration site or animal quarantine recommendations, respectively, were also
      included. Nine hundred and fifty-two physicians and 125 veterinarians responded.
      Veterinarians were more likely to select the correct vectors and clinical signs
      in animals than physicians. Physicians more likely selected the correct
      transmission routes. Less than half of physicians identified the correct PEP
      schedule (39.4%) and administration site (49.0%). Half of veterinarians (50.0%)
      correctly identified quarantine length for wildlife-exposed vaccinated dogs
      compared to only 19.4% for unvaccinated dogs. Several knowledge gaps were
      identified amongst physicians and veterinarians. Due to the fatal nature of
      rabies, it is important that all healthcare providers have an understanding of
      current recommendations. Health departments can work to correct these gaps and
      serve as a bridge between human and animal healthcare professionals.

PMID- 30099850
TI  - Heterogeneity of fatty acid metabolism in breast cancer cells underlies
      differential sensitivity to palmitate-induced apoptosis.
AB  - Breast cancer (BrCa) metabolism is geared toward biomass synthesis and
      maintenance of reductive capacity. Changes in glucose and glutamine metabolism in
      BrCa have been widely reported, yet the contribution of fatty acids (FAs) in BrCa
      biology remains to be determined. We recently reported that adipocyte coculture
      alters MCF-7 and MDA-MB-231 cell metabolism and promotes proliferation and
      migration. Since adipocytes are FA-rich, and these FAs are transferred to BrCa
      cells, we sought to elucidate the FA metabolism of BrCa cells and their response
      to FA-rich environments. MCF-7 and MDA-MB-231 cells incubated in serum-containing
      media supplemented with FAs accumulate extracellular FAs as intracellular
      triacylglycerols (TAG) in a dose-dependent manner, with MDA-MB-231 cells
      accumulating more TAG. The differences in TAG levels were a consequence of
      distinct differences in intracellular partitioning of FAs, and not due to
      differences in the rate of FA uptake. Specifically, MCF-7 cells preferentially
      partition FAs into mitochondrial oxidation, whereas MDA-MB-231 cells partition
      FAs into TAG synthesis. These differences in intracellular FA handling underpin
      differences in the sensitivity to palmitate-induced lipotoxicity, with MDA-MB-231
      cells being highly sensitive, whereas MCF-7 cells are partially protected. The
      attenuation of palmitate-induced lipotoxicity in MCF-7 cells was reversed by
      inhibition of FA oxidation. Pretreatment of MDA-MB-231 cells with FAs increased
      TAG synthesis and reduced palmitate-induced apoptosis. Our results provide novel
      insight into the potential influences of obesity on BrCa biology, highlighting
      distinct differences in FA metabolism in MCF-7 and MDA-MB-231 cells and how lipid
      rich environments modulate these effects.

PMID- 30099852
TI  - Weight-adjusted tinzaparin for the prevention of venous thromboembolism after
      bariatric surgery.
AB  - : Essentials The optimal dose and duration of thromboprophylaxis after bariatric
      surgery are unclear. We evaluated the safety of weight-adjusted tinzaparin
      prophylaxis in 1212 patients. In-hospital rates of venous thromboembolism and
      major bleeding were 0.2% and 1.8% respectively. In a sub-set of patients, trough
      anti-Xa levels did not show excessive anticoagulant activity. SUMMARY: Background
      Patients undergoing bariatric surgery are at moderate to high risk of venous
      thromboembolism (VTE). The optimal dose and duration of anticoagulant prophylaxis
      is uncertain. Objective To evaluate the safety of extended-duration weight
      adjusted tinzaparin after bariatric surgery. Patients/methods We conducted a
      single-center retrospective cohort study of consecutive patients undergoing
      bariatric surgery who received weight-adjusted tinzaparin 4500-14 000 IU daily
      (75 IU kg-1 rounded to the nearest prefilled syringe) for 10 days after surgery
      (7-9 days post-hospital discharge). Primary safety outcomes were the frequency of
      VTE and major bleeding within 30 days of surgery in patients receiving at least
      one dose of tinzaparin. Results A total of 1279 patients undergoing bariatric
      surgery between July 2009 and December 2012 were reviewed, of whom 1212 received
      weight-adjusted tinzaparin. Safety outcomes were collected for 819 patients at 30
      days, and for 1212 patients in-hospital only. The median age was 45.0 years,
      median weight was 130.0 kg and 98.8% of patients underwent gastric bypass or
      sleeve gastrectomy. In patients completing 30 days of follow-up, VTE occurred in
      4/819 (0.5%) and major bleeding occurred in 13/819 patients (1.6%). In-hospital
      rates of VTE and major bleeding during surgical admission were 3/1212 (0.2%) and
      22/1212 (1.8%), respectively. Conclusions Extended thromboprophylaxis with weight
      adjusted tinzaparin appears to be a safe strategy after bariatric surgery, with
      low rates of postoperative VTE and major bleeding.

PMID- 30099851
TI  - Metabolomic profiling of human lung tumor tissues - nucleotide metabolism as a
      candidate for therapeutic interventions and biomarkers.
AB  - Although metabolomics has attracted considerable attention in the field of lung
      cancer (LC) detection and management, only a very limited number of works have
      applied it to tissues. As such, the aim of this study was the thorough analysis
      of metabolic profiles of relevant LC tissues, including the most important
      histological subtypes (adenocarcinoma and squamous cell lung carcinoma). Mass
      spectrometry-based metabolomics, along with genetic expression and histological
      analyses, were performed as part of this study, the widest to date, to identify
      metabolic alterations in tumors of the most relevant histological subtypes in
      lung. A total of 136 lung tissue samples were analyzed and 851 metabolites were
      identified through metabolomic analysis. Our data show the existence of a clear
      metabolic alteration not only between tumor vs. nonmalignant tissue in each
      patient, but also inherently intrinsic changes in both AC and SCC. Significant
      changes were observed in the most relevant biochemical pathways, and nucleotide
      metabolism showed an important number of metabolites with high predictive
      capability values. The present study provides a detailed analysis of the
      metabolomic changes taking place in relevant biochemical pathways of the most
      important histological subtypes of LC, which can be used as biomarkers and also
      to identify novel targets.

PMID- 30099853
TI  - Verification of Kumamoto Declaration 2013 and Glycemic Targets for Elderly
      Patients with Diabetes in Japan for prevention of diabetic complications: A
      retrospective longitudinal study using outpatient clinical data.
AB  - AIMS/INTRODUCTION: The present study examined the association between the onset
      of micro- and macroangiopathy in type 2 diabetes mellitus patients and levels of
      glycated hemoglobin (HbA1c) described in the Evidence-based Practice Guideline
      for the Treatment for Diabetes in Japan 2013 or those indicated in the Japan
      Diabetes Society and the Japan Geriatrics Society Joint Committee on Improving
      Care for Elderly Patients with Diabetes. MATERIALS AND METHODS: Patients with
      type 2 diabetes mellitus who visited the outpatient clinic at Kawasaki Medical
      School Hospital between 2000 and 2016 and received follow up for >2 years were
      eligible for the present study. Two datasets, comprising 2,424 or 3,316 patients
      without micro- or macroangiopathy at the start of follow up, were used,
      respectively. The Cox model was used in two categories of patients, younger and
      elderly, with the dividing line set at the age of 65 years. RESULTS: For the
      prevention of microangiopathy, in all patients, there was found to be no
      advantage in controlling HbA1c at a level of <6.0% based on the categories in the
      Evidence-based Practice Guideline for the Treatment for Diabetes in Japan 2013,
      and there was found to be a disadvantage in maintaining HbA1c >=8.5% based on the
      categories in the Japan Diabetes Society and the Japan Geriatrics Society Joint
      Committee on Improving Care for Elderly Patients with Diabetes guideline. For the
      prevention of macroangiopathy in younger patients, there seemed to be an
      advantage in maintaining HbA1c within the range of 6.0-6.9% and <7.0% based on
      the Evidence-based Practice Guideline for the Treatment for Diabetes in Japan
      2013 and the Japan Diabetes Society and the Japan Geriatrics Society Joint
      Committee on Improving Care for Elderly Patients with Diabetes, respectively.
      CONCLUSIONS: In all type 2 diabetes mellitus patients, average HbA1c should be
      maintained <7.0% to prevent microangiopathy. However, in elderly patients, no
      optimal target for preventing macroangiopathy was found, in contrast to the
      younger patients in the present study.

PMID- 30099855
TI  - Search for altered imprinting marks in Mayer-Rokitansky-Kuster-Hauser patients.
AB  - BACKGROUND: Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) is the second most
      common cause of primary amenorrhea and characterized by absence of the uterus and
      the upper part of the vagina. The etiology of MRKH is mainly unknown but a
      contribution of genomic alterations is probable. A molecular disturbance so far
      neglected in MRKH research is aberrant methylation at imprinted loci. In fact,
      MRKH has been reported in patients with the imprinting disorder Silver-Russell
      syndrome. METHODS: We report on a rare patient with MRKH and SRS due to an ICR1
      hypomethylation in 11p15.5. On the basis of this observation we screened a large
      cohort of MRKH patients (n > 100) for aberrant methylation at nine imprinted
      loci. RESULTS: We failed to detect any epimutation, thus we conclude that
      imprinting defects at least at the currently known disease-relevant imprinted
      loci do not contribute to the isolated MRKH phenotype. However, it cannot be
      excluded that altered methylation marks at other loci are involved in the
      etiology of MRKH. CONCLUSION: The molecular basis for MRKH remains unclear in the
      majority of patients, but future studies on the association between MRKH and ICR1
      hypomethylation/SRS will to enlighten the role of epigenetics in the etiology of
      MRKH.

PMID- 30099856
TI  - Factors influencing refusing of Flu Vaccination among pregnant women in Italy:
      health care workers's role.
AB  - BACKGROUND: Pregnant women are at increased risk of influenza complications.
      Influenza vaccine provides them a substantial protection. The aim of this study
      was to investigate determinants associated with non-adherence to influenza
      vaccine recommendations in pregnant women in Italy. METHODS: A cross-sectional
      study has been carried out among pregnant women attending their follow-up visit
      in some mother and child services in a Region of Italy from October 2016 to
      January 2017. THE STUDY PROTOCOL WAS APPROVED BY THE LOCAL RESEARCH ETHICS: A
      self-administered close-ended questionnaire has been administered to the pregnant
      women. Differences in background, socio-demographic characteristics, knowledge
      and attitudes towards flu vaccine were tested in vaccinated and unvaccinated
      women. Multilevel analysis was performed to control for confounding factors.
      RESULTS: 366 women answered the survey (97% response rate) and 96.1% (348)
      declared of being unvaccinated against influenza during the 2016-2017 influenza
      season. Frequent reasons for refusing vaccination were drugs objection and
      concerns about vaccines' effects. According to the refusal attitude, influenza
      knowledge were low in the group. Moreover, analysis showed that low adherence to
      vaccination is associated to lacking promotion of vaccination to pregnant women
      carried out by healthcare workers (p<0.005). CONCLUSION: Health care workers have
      a key role in assisting women during the gestational period, so their active
      involvement in vaccination promotion is essential. It is necessary to improve
      health care workers' knowledge about vaccine relevance in protecting pregnancy
      and their communication skills to properly inform pregnant women. This article is
      protected by copyright. All rights reserved.

PMID- 30099854
TI  - Telbivudine in chronic lymphocytic myocarditis and human parvovirus B19
      transcriptional activity.
AB  - AIMS: Myocarditis is often associated with parvovirus B19 (B19V) persistence,
      which can induce vascular damage. Based on the antiviral and anti-inflammatory
      properties of telbivudine, we aimed to evaluate its efficacy to protect B19V
      infected endothelial cells in vitro and to treat chronic lymphocytic myocarditis
      patients with B19V transcriptional activity. METHODS AND RESULTS: We evaluated
      the endothelial-protective potential of telbivudine in human microvascular
      endothelial cells-1, which were infected with B19V. Treatment with 10 ng/mL of
      telbivudine decreased the B19V-induced endothelial cell apoptosis and endothelial
      to-mesenchymal transition. Along with this finding, telbivudine reduced the
      expression of transforming growth factor-beta1 and of tenascin-C. The endothelial
      protective properties of telbivudine were also found in tumour necrosis factor
      alpha-stressed human microvascular endothelial cells-1. In addition, oxidative
      stress in angiotensin II-stressed and transforming growth factor-beta1-stressed
      HL-1 cardiomyocytes and fibroblasts, respectively, was reduced upon telbivudine
      treatment, illustrating that telbivudine exerts multimodal protective effects.
      Based on these in vitro findings, four patients severely suffering from an
      endomyocardial biopsy-proven myocarditis associated with B19V transcriptional
      activity (VP1/VP2-mRNA positive) were treated with telbivudine (600 mg/dL) for 6
      months in a single-patient-use approach. Follow-up biopsies 6 months after
      treatment showed that VP1/VP2-mRNA levels and CD3 cells decreased in all patients
      and were associated with an improvement in ejection fraction and New York Heart
      Association class. These findings were paralleled by a drop in tenascin-C
      expression as shown via matrix-assisted laser desorption ionization-imaging mass
      spectrometry. CONCLUSIONS: Telbivudine exerts endothelial-protective effects in
      B19V-infected endothelial cells and improves chronic myocarditis associated with
      B19V transcriptional activity. These findings will be further evaluated in the
      clinical exploratory trial: the PreTopic study.

PMID- 30099857
TI  - Programmed environmental illumination during autologous stem cell transplantation
      hospitalization for the treatment of multiple myeloma reduces severity of
      depression: A preliminary randomized controlled trial.
AB  - BACKGROUND: Over a third of multiple myeloma (MM) patients report clinical levels
      of depression during autologous stem cell transplant (ASCT) hospitalization. We
      report preliminary results from a randomized clinical trial investigating the
      effect of Programmed Environmental Illumination (PEI) of hospital rooms on
      depression. METHODS: Patients (N = 187) scheduled to receive an ASCT were
      assessed for eligibility. Those who met study eligibility criteria (n = 44) were
      randomly assigned to one of two PEI conditions involving delivery of either
      circadian active bright white light (BWL) or circadian inactive dim white light
      (DWL) throughout the room from 7 to 10 am daily during hospitalization. Patients
      completed the Center for Epidemiological Studies Depression Scale (CES-D) prior
      to hospitalization, at days 2 and 7 post-transplant, and on the third day of
      engraftment. RESULTS: General linear model analyses revealed no difference
      between the groups in CES-D total score at baseline (P = 0.7859). A longitudinal
      linear mixed model analysis revealed a significant interaction between time of
      assessment and light condition [F(3,107) = 2.90; P = 0.0386; n2  = 0.08)],
      indicating that PEI prevented the development of depression during
      hospitalization, with effects reaching significance by the third day of
      engraftment. At the third day of engraftment, 68.4% of the participants in the
      DWL comparison condition met the criteria for clinically significant depression
      compared to 42.1% in the BWL condition. CONCLUSION: These findings demonstrate
      that PEI using BWL during MM ASCT hospitalization is effective in reducing the
      development of depression. Future studies should examine the mechanisms whereby
      PEI improves depression.

PMID- 30099858
TI  - Hand selection in a preferential reaching task: The effects of object location,
      orientation, and task intention in preadolescent children.
AB  - INTRODUCTION AND METHODS: Hand selection was assessed in preadolescent children
      (ages 9-11) within a preferential reaching task to delineate the effects of
      object location, orientation, and task intention on the assessment procedure and
      compared to data previously acquired from young adults. RESULTS: The observed
      differences support the notion that children are still in a process of refining
      their movements in attempt to discern the most efficient and effective patterns
      of behavior. Notwithstanding differences in performance, similarities between
      preadolescents and young adults also emerged. Greater right-hand selection in
      right space and when the handle was oriented to the right indicate that object
      proximity and orientation influence efficiency and thus constrain hand selection
      in unimanual object manipulation and role-differentiated bimanual manipulation.
      CONCLUSIONS: Together, findings add to our understanding of hand preference,
      unimanual and bimanual object manipulation.

PMID- 30099859
TI  - Decreased pain and improved dynamic knee instability mediate the beneficial
      effect of wearing a soft knee brace on activity limitations in persons with knee
      osteoarthritis.
AB  - OBJECTIVE: To evaluate whether improvement of proprioception, pain or dynamic
      knee instability mediate the effect of wearing a soft knee brace on activity
      limitations in persons with knee osteoarthritis (OA). METHODS: Exploratory
      analysis from 44 participants with knee OA and self-reported knee instability in
      a laboratory trial evaluating the effect of wearing a commercially available soft
      knee brace. Activity limitations were assessed with the 10-meter walk test and
      the Get up and Go test. Knee joint proprioception was assessed by an active joint
      position sense test; pain was assessed with the Numeric Rating Scale (NRS);
      pressure pain threshold (PPT) was assessed with a hand-held pressure algometer;
      dynamic knee instability was expressed by the Perturbation Response, i.e. a
      measure reflecting a deviation in mean knee varus-valgus angle after a controlled
      mechanical perturbation on a treadmill, with respect to level walking. Mediation
      analysis was conducted with the product of coefficients approach. Confidence
      intervals were calculated with a bootstrap procedure. RESULTS: A decrease of pain
      (NRS) and a decrease of dynamic knee instability mediated the effect of wearing a
      soft knee brace on reduction of activity limitations (p < 0.05), while changes of
      proprioception and PPT did not mediate this effect (p > 0.05). CONCLUSION: This
      study shows that decreased pain and reduced dynamic knee instability are pathways
      via which wearing a soft knee brace decreased activity limitations in persons
      with knee OA. This article is protected by copyright. All rights reserved.

PMID- 30099861
TI  - Effects of language, insurance and race/ethnicity on measurement properties of
      the PROMIS Physical Function Short Form 10a in rheumatoid arthritis.
AB  - OBJECTIVE: Most studies evaluating patient-reported outcomes such as the PROMIS
      Physical Function Short Form 10a (PF10a) in rheumatoid arthritis (RA) have been
      performed in Caucasian and English-speaking populations. We assessed the
      measurement properties of the PF10a in a racially/ethnically diverse population
      with RA. We determined the effect of non-English language proficiency, insurance
      status and race/ethnicity, on the validity and responsiveness of the PF10a.
      METHODS: Data were abstracted from electronic health records for all RA patients
      seen in a university-based rheumatology clinic between 2013 and 2017. We
      evaluated the PF10a's use, floor and ceiling effects, and construct validity
      across categories of language preference, insurance and race/ethnicity. We used
      standardized response means and linear mixed-effects models to evaluate the
      responsiveness of the PF10a to longitudinal changes in the Clinical Disease
      Activity Index (CDAI) across population subgroups. RESULTS: We included 595
      patients in a cross-sectional analysis of validity and 341 patients in
      longitudinal responsiveness analyses of the PF10a. The PF10a had acceptable floor
      and ceiling effects and was successfully implemented. We observed good construct
      validity and responsiveness to changes in CDAI among whites, English-speakers and
      privately-insured patients. However, constructs evaluated by the PF10a were less
      correlated with clinical measures among Chinese-speakers and Hispanics, and less
      sensitive to clinical improvements among Medicaid patients and Spanish-speakers.
      CONCLUSION: While the PF10a has good measurement properties and is both practical
      and acceptable for implementation in routine clinical practice, we also found
      important differences across racial/ethnic groups and those with limited English
      proficiency that warrant further investigation. This article is protected by
      copyright. All rights reserved.

PMID- 30099863
TI  - Jejunal diverticulosis.

PMID- 30099860
TI  - Dynamics of circulating microRNAs as a novel indicator of clinical response to
      neoadjuvant chemotherapy in breast cancer.
AB  - BACKGROUND: Circulating microRNAs (miRNAs) have been indicated as predictive
      biomarkers in breast cancer. We aimed to explore the association of plasma miRNA
      dynamics with response to neoadjuvant chemotherapy (NCT) and disclose early
      markers for predicting sensitivity. METHODS: One hundred and nine patients with
      operable or locally advanced breast cancer, who participated in a prospective
      clinical trial and received NCT, were analyzed. Blood samples were collected
      before random assignment, after two cycles of chemotherapy (C2) and before
      surgery. Based on their clinical response, the patients were defined as chemo
      sensitive or insensitive. First, baseline and preoperative samples of selected
      cases from both groups were screened via TaqMan miRNA array for candidate miRNAs.
      Afterward all the biospecimens were tested for the candidate miRNAs (miR-222, miR
      20a, miR-451, miR-9, miR-34a, miR-155, and miR-145) by quantitative real-time
      PCR. Finally, logistic regression model was utilized to determine the predictive
      value of baseline/C2 expression of these miRNAs. RESULTS: Based on the results of
      microRNA profiling, seven miRNAs were selected for further validation. In the
      HR+/HER2- cohort (n = 51) dynamics of three miRNAs, including miR-222, miR-20a,
      and miR-451, were associated with chemo-sensitivity. Importantly, across all the
      three subtypes we consistently identified chemo-induced decrease in plasma miR
      34a in the insensitive patients. Finally, baseline miR-222 overexpression (OR =
      6.422, P = 0.049), C2 miR-20a up-regulation (OR = 0.144, P = 0.021) and C2 miR
      451 down-regulation (OR = 8.213, P = 0.012) were predictive markers of response
      to NCT in HR+/HER2- breast cancer. CONCLUSIONS: We described that dynamics of
      circulating miRNAs might help predict clinical response to NCT in breast cancer.

PMID- 30099864
TI  - Effects of botulinum toxin injection on systemic sclerosis-related digital
      ulcers.

PMID- 30099862
TI  - Clinical and laboratory factors related to acute isolated vertigo or dizziness
      and cerebral infarction.
AB  - OBJECTIVE: To clarify the relationship of clinical factors with isolated vertigo
      or dizziness of cerebrovascular origin. METHODS: Clinical data of patients
      admitted in East Hospital from Jan. 2015 to Apr. 2016, whose complaint were acute
      vertigo or dizziness were retrospectively collected. All patients arrived at the
      emergency department within 24 hr of symptom onset, had no acute ischemic lesion
      first CT and NIHSS score of 0. Patients were divided into cerebral infarction
      group and noncerebral infarction group according to subsequent cerebral imaging
      results and clinical and laboratory factors related to cerebral infarction were
      analyzed. RESULT: 51.6% of patients were female (n = 141). 46 patients (16.8%)
      were diagnosed with acute cerebral infarction. Baseline demographic data of the
      two groups was not significantly different. Univariate analysis found that
      history of smoking (p = 0.009), headache (p = 0.028), unsteadiness (p = 0.009),
      neuron specific enolase (p = 0.001), and vertebral artery abnormalities found on
      imaging (p = 0.009) were the significant difference between two groups. Increased
      neuron specific enolase (p = 0.005) and an abnormal vertebral artery (p = 0.044)
      were significant on multivariate analysis. CONCLUSIONS: 16.8% of acute isolated
      vertigo or dizziness presentations were diagnosed with acute cerebral infarction.
      Increased serum neuron specific enolase and vertebral artery abnormalities were
      the strongest indicators of acute cerebral infarction.

PMID- 30099865
TI  - Cardiac computed tomography reveals aortic valve perforation in a patient with
      severe aortic regurgitation.

PMID- 30099866
TI  - Fever of unknown origin caused by intrathyroidal thymic carcinoma.

PMID- 30099867
TI  - Reduction of Background Generated from Template-Template Hybridizations in the
      Exponential Amplification Reaction.
AB  - The Exponential Amplification Reaction (EXPAR) enables isothermal amplification
      of nucleic acids. However, applications of EXPAR for the amplification of trace
      amounts of nucleic acids are hindered by high background. The mechanism of
      background generation is currently not well understood, although it is assumed to
      involve nonspecific extension of EXPAR templates by DNA polymerase. We present
      here a study of the mechanisms of triggering EXPAR background amplification. We
      show that interactions of EXPAR templates lead to background amplification via
      polymerase extension of the templates. We further designed and tested two
      strategies to minimize background amplification: blocking of the 3'-end of the
      template and sequence-independent weakening of the template-template
      interactions. Sequence-specific 3'-end blocking showed reduced background,
      suggesting that 3'-end template interactions are a contributing factor to
      background amplification. Sequence-independent binding of the whole EXPAR
      template substantially reduced background amplification by competing with
      template-template interactions along the entire template sequence. This study
      provided evidence that nonspecific template interactions and extension by DNA
      polymerase triggered the amplification of background in EXPAR. The addition of
      single stranded binding protein to bind nonspecifically with the EXPAR template
      decreased background by 3 orders of magnitude.

PMID- 30099868
TI  - Conducting Polymer Coating on a High-Voltage Cathode Based on Soft Chemistry
      Approach toward Improving Battery Performance.
AB  - The surface of a 5 V class LiNi0.5Mn1.5O4 particle is modified with poly(3,4
      ethylenedioxythiophene) (PEDOT) conducting polymer by utilizing the hydrophobic
      characteristics of the 3,4-ethylenedioxythiophene (EDOT) monomer and the tail
      group of cetyl trimethyl ammonium bromide (CTAB) surfactants, in addition to the
      electrostatic attraction between cationic CTAB surfactant and cathode materials
      with a negative zeta potential in aqueous solution. With this novel concept, we
      design and prepare a uniform EDOT monomer layer on the cathode materials, and
      chemical polymerization of the EDOT coating layer is then carried out to achieve
      PEDOT-coated cathode materials via a simple one-pot preparation process. This
      uniform conducting polymer layer provides notable improvement in the power
      characteristics of electrodes, and stable electrochemical performance can be
      obtained especially at severe operating conditions such as the fully charged
      state and elevated temperatures owing to the successful suppression of the side
      reaction between the oxide particle and the electrolyte as well as the
      suppression of Mn dissolution from the oxide material.

PMID- 30099869
TI  - Synthesis of Enantioenriched Bromohydrins via Divergent Reactions of Racemic
      Intermediates from Anchimeric Oxygen Borrowing.
AB  - We report a chiral phosphoric acid catalyzed bromocyclization/regiodivergent
      reaction of racemic intermediates sequence, which is enabled by anchimeric oxygen
      borrowing. Different types of alkenes are applicable, and both enantiomers of the
      bromohydrin products were obtained in generally excellent yields and
      enantioselectivities. In addition, an example of enantioconvergent synthesis from
      the two isomeric products is presented.

PMID- 30099870
TI  - In Situ Kinetic and Thermodynamic Growth Control of Au-Pd Core-Shell
      Nanoparticles.
AB  - One-pot wet-chemical synthesis is a simple way to obtain nanoparticles (NPs) with
      a well-defined shape and composition. However, achieving good control over NP
      synthesis would require a comprehensive understanding of the mechanisms of NP
      formation, something that is challenging to obtain experimentally. Here, we study
      the formation of gold (Au) core-palladium (Pd) shell NPs under kinetically and
      thermodynamically controlled reaction conditions using in situ liquid cell
      transmission electron microscopy (TEM). By controlling the reaction temperature,
      we demonstrate that it is possible to tune the shape of Au nanorods to Au-Pd
      arrow-headed structures or to cuboidal core-shell NPs. Our in situ studies show
      that the reaction temperature can switch the Pd shell growth between the
      kinetically and thermodynamically dominant regimes. The mechanistic insights
      reported here reveal how the reaction temperature affects the packing of the
      capping agents and how the facet selection of depositing shell atoms drives the
      shell formation under different kinetic conditions, which is useful for
      synthesizing NPs with greater design flexibility in shape and elemental
      composition for various technological applications.

PMID- 30099872
TI  - Estimation of Exposure to Organic Flame Retardants via Hand Wipe, Surface Wipe,
      and Dust: Comparability of Different Assessment Strategies.
AB  - This study aimed to investigate the exposure of three occupational populations
      (i.e., office worker, taxi drivers, and security guards) to flame retardants by
      comparing different sampling approaches (i.e., hand wipe, surface wipe, and
      dust). Hand wipe samples were collected from 68 participants from three
      populations in Beijing, China. Dust and/or surface wipes were also sampled from
      their respective occupational workplaces. Ten phosphorus flame retardants (PFRs),
      two novel brominated flame retardants (NBFRs) and eight polybrominated diphenyl
      ethers (PBDEs) were analyzed. BDE209, decabromodiphenylethane (DBDPE),
      tris(chloropropyl) phosphate isomers (?TCPP), tris(2-chloroethyl) phosphate
      (TCEP) and triphenyl phosphate (TPHP) were detected in at least 95% of the
      samples, collectively accounting for over 90% of the total concentrations in each
      type of samples. Concentrations and composition profiles of flame retardants
      differed in hand wipes of the three populations with summed level of all target
      compounds (?FRs) ranked as taxi drivers > office workers > security guards. Most
      FRs in hand wipes were significantly correlated with those in surface wipes,
      whereas the correlations between hand wipes and dust are weak. Estimated exposure
      to FRs via dust ingestion and dermal absorption for each population varied when
      using different types of samples for exposure assessment, suggesting the
      importance of sampling strategy selection. Estimation via hand wipes indicated
      that taxi drivers were subjected to greater exposure to PFRs among three
      populations, while office workers were subjected to greater BFR exposure. Our
      data suggest hand wipes have the potential of being standardized into a
      noninvasive method for evaluating human exposure to environmental contaminants
      across different populations.

PMID- 30099871
TI  - Progress on Identifying and Characterizing the Human Proteome: 2018 Metrics from
      the HUPO Human Proteome Project.
AB  - The Human Proteome Project (HPP) annually reports on progress throughout the
      field in credibly identifying and characterizing the human protein parts list and
      making proteomics an integral part of multiomics studies in medicine and the life
      sciences. NeXtProt release 2018-01-17, the baseline for this sixth annual HPP
      special issue of the Journal of Proteome Research, contains 17 470 PE1 proteins,
      89% of all neXtProt predicted PE1-4 proteins, up from 17 008 in release 2017-01
      23 and 13 975 in release 2012-02-24. Conversely, the number of neXtProt PE2,3,4
      missing proteins has been reduced from 2949 to 2579 to 2186 over the past two
      years. Of the PE1 proteins, 16 092 are based on mass spectrometry results, and
      1378 on other kinds of protein studies, notably protein-protein interaction
      findings. PeptideAtlas has 15 798 canonical proteins, up 625 over the past year,
      including 269 from SUMOylation studies. The largest reason for missing proteins
      is low abundance. Meanwhile, the Human Protein Atlas has released its Cell Atlas,
      Pathology Atlas, and updated Tissue Atlas, and is applying recommendations from
      the International Working Group on Antibody Validation. Finally, there is
      progress using the quantitative multiplex organ-specific popular proteins
      targeted proteomics approach in various disease categories.

PMID- 30099873
TI  - The Chemistry of Europium(III) Encountering DNA: Sprouting Unique Sequence
      Dependent Performances for Multifunctional Time-Resolved Luminescent Assays.
AB  - Screening functional DNA that can fruitfully interact with metal ions is a long
      standing hot topic in the fields of biotechnology, medicine, and DNA-based
      sensors. In this paper, we focus on the chemistry of europium(III) (Eu) coupled
      with single-stranded DNA (ssDNA), and we innovatively unveil that cytosine- and
      thymine-rich ssDNA oligomers (e.g., C16 and T16) can be effective antenna ligands
      to sensitize the luminescence of Eu. Luminescence lifetime spectroscopy, circular
      dichroic (CD) spectroscopy, and isothermal titration calorimetry (ITC) have been
      used to systematically characterize the interaction involved between Eu and
      ssDNA. In light of the resultant sequence-dependent performances, the long
      luminescence lifetime Eu/ssDNA-based label-free and versatile probes are further
      devised as a pattern distinction system for time-resolved luminescent (TRL)
      sensing applications. The interactions of metal ions and ssDNA can distinctively
      shift the antenna effect of ssDNA toward Eu as accessible pattern signals. As a
      result, as few as two Eu/ssDNA label-free TRL probes can discriminate 17 metal
      ions via principal component analysis (PCA). In addition, thiols can readily
      capture metal ions to switch the luminescence of Eu/ssDNA probes initially
      altered by metal ions. Hence, four Eu/ssDNA-metal ion ensembles are demonstrated
      to be a powerful label-free TRL sensor array for pattern differentiation of eight
      thiols and even chiral recognition of cysteine enantiomers with different
      concentrations. Moreover, the sensitive TRL detection of thiols in biofluids can
      be successfully realized by using our method, promising its potential practical
      usage. This is the first report of a ssDNA-sensitized Eu-based TRL platform for
      label-free yet multifunctional background-free sensing and would open a door for
      sprouting of more novel lanthanide ion/DNA-relevant strategies toward widespread
      applications.

PMID- 30099874
TI  - Sorption, Aerobic Biodegradation, and Oxidation Potential of PFOS Alternatives
      Chlorinated Polyfluoroalkyl Ether Sulfonic Acids.
AB  - Global phase out of perfluorooctanesulfonic acid (PFOS) has led to increasing
      production of alternatives such as the chlorinated polyfluoroalkyl ether sulfonic
      acids (Cl-PFESAs) for which little is known on their environmental fate. In this
      study, sorption by soils, aerobic soil biodegradation, and oxidation potential of
      6:2 Cl-PFESA (9-chlorohexadecafluoro-3-oxanonane-1-sulfonate) and 8:2 Cl-PFESA (9
      chlorooctadecafluoro-3-oxanonane-1-sulfonate) were evaluated. 6:2 Cl-PFESA
      sorption was quantified for aqueous and acetone/water solutions, whereas 8:2
      PFESA could only be accurately measured in acetone/water solutions. The log
      linear cosolvency model was applied and validated to estimate sorption of 8:2 Cl
      PFESA. Only soil organic carbon (OC, 0.76-4.30%) was highly and positively
      correlated to sorption of the Cl-PFESAs ( R2 > 0.96). The resulting log Koc
      values (OC-normalized sorption coefficients) are 4.01 +/- 0.09 ( n = 6) and 5.54
      +/- 0.05 ( n = 4) L kg-1 for 6:2 Cl-PFESA and 8:2 Cl-PFESA, respectively. Aerobic
      biodegradation in a loam soil at 24 +/- 0.5  degrees C showed negligible
      degradation of both Cl-PFESAs. Cl-PFESAs also remained unchanged in an unbuffered
      heat (50  degrees C)-activated 42 mM persulfate oxidation treatment. Therefore,
      Cl-PFESAs are equally recalcitrant as PFOS in addition to being more sorptive,
      thus with a higher bioaccumulation potential for a similar alkyl chain length.

PMID- 30099875
TI  - Sources and Fate of Cyclic Phenylmethylsiloxanes in One Municipal Wastewater
      Treatment Plant and Biosolids-Amended Soil.
AB  - cis-/ trans-2,4,6-Triphenyl-2,4,6-trimethylcyclotrisiloxanes ( cis-P3 and trans
      P3) and cis-/ trans-2,4,6,8-tetraphenyl-2,4,6,8-tetramethylcyclotetrasiloxanes (
      cis-P4 and trans-P4a,b,c) were detected in personal care products [<LOD-54.2
      MUg/g, detection frequencies (df) = 14.5-15.5%, n = 110] collected from a Chinese
      city, suggesting their potential release to local municipal wastewater treatment
      plant (WWTP). In the local WWTP, per capita mass loadings of P3 and P4 were 43.4
      340 MUg/d in influents, while neither P3 nor P4 was detected in effluents. Due to
      large solid/water distribution coefficients (apparent Log Kd = 3.42-3.99),
      sorption to sludge had a dominant contribution (95.6-99.2%) to
      phenylmethylsiloxanes removal in the WWTP. As amended by biosolids containing
      phenylmethylsiloxanes [66.2 ng/g to 2.63 MUg/g dw (dry weight)] from this WWTP,
      concentrations (<LOD -255 ng/g dw, df = 27.5-52.5%, n = 120) of six
      phenylmethylsiloxane isomers in soils from one commercial forest were
      significantly higher than those (<LOD) in the reference area without biosolids
      application, but no increasing trend was found at six sampling events during July
      2015 to February 2017. Simulated experiments indicated that hydrolysis half-lives
      of phenylmethylsiloxanes (1.50-6.50 d for P3, 16.5-65.4 d for P4) in soil were
      4.74-46.3 times shorter than volatilization half-lives (51.9-120 d for P3, 158
      376 d for P4). For both cyclic phenylmethylsiloxanes, their trans-isomers had
      lower (1.14-1.82 times) degradation rates than their cis-isomers.

PMID- 30099876
TI  - A Stimuli-Responsive Molecular Capsule with Switchable Dynamics, Chirality, and
      Encapsulation Characteristics.
AB  - In this study, we report the preparation, conformational dynamics, and
      recognition characteristics of novel molecular capsule 1 comprising a bowl-shaped
      framework conjugated to a tris(2-pyridylmethyl)amine (TPA) lid. With the
      assistance of experiment (1H NMR spectroscopy) and theory (MM and DFT) we found
      that C3 symmetric 1 is poorly preorganized with three pyridines at the rim
      adopting a propeller-like orientation and undergoing P-to- M (or vice versa)
      stereoisomerization (Delta G? < 8 kcal/mol, VT 1H NMR). Capsule 1 binds CH4,
      CH3Cl, CH2Cl2, CHCl3, and CCl4 with Ka < 7 M-1. Protonation of 1 with HCl,
      however, gives [1.H]-Cl, with the solid-state structure showing the TPA lid being
      "flattened" and the +N-H---Cl hydrogen-bonded group residing outside.
      Importantly, the P-to- M stereoisomerization would for [1.H]-Cl occur with Delta
      G? = 11 kcal/mol (VT 1H NMR). Less dynamic and more preorganized [1.H]-Cl binds
      CH4, CH3Cl, CH2Cl2, CHCl3, and CCl4 guests with a greater affinity ( Ka = 100-400
      M-1) than 1. The results of our studies suggest that the complexation of
      increasingly larger guests takes place in an induced-fit fashion, with [1.H]-Cl
      (a) elongating along its vertical axis and concurrently potentially (b) twisting
      pyridines from P into M (and vice versa) orientation. The addition of Et3N to
      [1.H]-Cl?CH2Cl2 causes deprotonation of the capsule and the release of CH2Cl2
      with the process being fully reversed after the addition of HCl. Allosteric
      capsule 1 with unique structural and dynamic characteristics is expected to, in
      the future, assist the construction of complex molecular machines and smart
      functional materials.

PMID- 30099877
TI  - Systematic Study of Photoluminescence Enhancement in Monolayer Molybdenum
      Disulfide by Acid Treatment.
AB  - Monolayer molybdenum disulfide (MoS2) is an atomically thin semiconducting
      material with a direct band gap. This physical property is attributable to
      atomically thin optical devices such as sensors, light-emitting devices, and
      photovoltaic cells. Recently, a near-unity photoluminescence (PL) quantum yield
      of a monolayer MoS2 was demonstrated via a treatment with a molecular acid,
      bis(trifluoromethane)sulfonimide (TFSI); however, the mechanism still remains a
      mystery. Here, we work on PL enhancement of monolayer MoS2 by treatment of
      Bronsted acids (TFSI and sulfuric acid (H2SO4)) to identify the importance of the
      protonated environment. In TFSI as an acid, different solvents-1,2-dichloroethane
      (DCE), acetonitrile, and water-were studied, as they show quite different acidity
      in solution. All of the solvents showed PL enhancement, and the highest was
      observed in DCE. This behavior in DCE would be due to the higher acidity than
      others have. Acids from different anions can also be studied in water as a common
      solvent. Both TFSI and H2SO4 showed similar PL enhancement (~4-8 enhancement) at
      the same proton concentration, indicating that the proton is a key factor to
      enhance the PL intensity. Finally, we considered another cation, Li+ from Li2SO4,
      instead of H2SO4, in water. Although Li and H atoms showed similar binding energy
      on MoS2 from theoretical calculations, Li2SO4 treatment showed little PL
      enhancement; only coexisting H2SO4 reproduced the enhancement. This study
      demonstrated the importance of a protonated environment to increase the PL
      intensity of monolayer MoS2. The study will lead to a solution to achieve high
      optical quality and to implementation for atomically thin optical devices.

PMID- 30099878
TI  - pH-Regulated Optical Performances in Organic/Inorganic Hybrid: A Dual-Mode Sensor
      Array for Pattern-Recognition-Based Biosensing.
AB  - Dual-mode optical assays are becoming more popular and attractive because they
      would provide robust detailed information in biochemical analysis. We herein
      unveil a novel dual-mode optical (i.e., UV-vis absorption and fluorescence)
      method for multifunctional sensing of phosphate compounds (PCs) (e.g.,
      nucleotides and pyrophosphate) based on pattern recognition, which innovatively
      employs only one kind of porphyrin/lanthanide-doped upconversion nanoparticles
      (Ln-UCNPs) hybrid integrated with a facile pH-regulated strategy as the sensor
      array. An easy-to-obtain porphyrin hydrate (tetraphenylporphyrin tetrasulfonic
      acid hydrate, TPPS) can assemble onto the ligand-free Ln-UCNPs to construct the
      organic/inorganic hybrid (TPPS/Ln-UCNPs), leading to a new absorption band to
      quench the upconversion fluorescence of Ln-UCNPs due to fluorescence resonance
      energy transfer (FRET). The dual-mode optical performances of TPPS/Ln-UCNPs are
      characteristically correlated with the pH in aqueous solution. Thus, as a proof
      of-concept design, three types of TPPS/Ln-UCNPs (TPPS/Ln-UCNPs4, TPPS/Ln
      UCNPs4.5, and TPPS/Ln-UCNPs5) were prepared by using buffers with different pH
      (at 4, 4.5, and 5) to form our proposed sensor array, which would result in
      individual dual-mode optical response patterns upon being challenged with PCs for
      their pattern recognition through a competitive mechanism between TPPS and PCs.
      The results show that three TPPS/Ln-UCNPs n sensors can successfully permit the
      sensitive detection of 14 PCs and differentiate them between different
      concentrations, as well as a mixture of them. The pH-dependent TPPS/Ln-UCNPs
      promises the simple, yet powerful discrimination of PCs via pattern recognition,
      would prospectively stimulate and expand the use of organic/inorganic hybrid
      toward more biosensing applications.

PMID- 30099879
TI  - Polymers at the Interface with Biology.

PMID- 30099880
TI  - The Cape Town Declaration on Access to Cardiac Surgery in the Developing World.

PMID- 30099881
TI  - Redo tricuspid valve operation in patients with 1st-generation mitral prostheses.
AB  - Background In patients with remarkably enlarged cardiac chambers and history of
      implantation of older types of mitral valve prosthesis, the considerations for
      reoperative tricuspid valve surgery are not limited to the risks of sternal
      reentry but also include the dilemma of whether to carry out prophylactic
      replacement of the normal functioning but outdated prosthesis or leave it in
      situ. Methods We reviewed our surgical strategy and postoperative 5-year follow
      up findings in two patients who underwent redo tricuspid surgery 3 to 4 decades
      after mechanical mitral valve replacement. Both patients presented with
      significant symptoms of progressive right heart failure due to severe tricuspid
      regurgitation, despite optimal medical therapy. Results We found the beating
      heart approach to be an effective and safe method for redo tricuspid surgery.
      Both first-generation mitral mechanical prostheses were not replaced and have
      remained well functional upon the patients' postoperative 5-year follow-up,
      respectively. Conclusion For patients with normal functioning first-generation
      mechanical mitral prostheses, whether to prophylactically replace the prosthesis
      should be based on an individualized risk-benefit analysis.

PMID- 30099882
TI  - Upper Extremity Subcutaneous Lymphatic Drainage "Lymphocentesis" for Symptom
      Relief in End-Stage Breast Cancer.
AB  - Lymphedema is a challenging condition that occurs as a complication to many life
      limiting medical conditions. It has a number of associated symptoms including
      pain, functional impairments, and emotional distress. Majority of treatment
      interventions have been studied and applied outside of the palliative care
      context. Subcutaneous drainage is a technique that has been used in some case
      reports for the lower extremity and sacrum with good results. This report
      describes an adapted technique of subcutaneous drainage for treating upper
      extremity lymphedema in the palliative setting.

PMID- 30099883
TI  - Workability of patients with HIV/AIDS in Northern Vietnam: a societal perspective
      on the impact of treatment program.
AB  - In Vietnam, the antiretroviral therapy (ART) program has been widely scaled up
      across the country since 2005, and now covers treatment for about half the HIV
      population. However, limited data exist about the workability and productivity
      outcome of ART in Vietnam. We aim to assess the employment status and work
      productivity among HIV patients taking ART in Northern Vietnam. A cross-sectional
      study was conducted in Hanoi and Nam Dinh with 1133 participants taking ART at
      the selected clinics. The Work Productivity and Activity Impairment
      Questionnaire: General Health (WPAI-GH) was applied. We found that 23% of
      patients with HIV/AIDS reported overall work productivity loss, and 12% had
      activity impairment. Among those having a job, their monthly income, however, was
      significantly lower than national averages 2806 thousand VND vs. 4120 thousand
      VND). The average education level of participants was low, with only 41.61%
      having greater than secondary education. Health problems and lower CD4 cell
      counts decreased workability of the patients while having a more dependent
      family, being a smoker or having a later HIV stage was associated with being less
      likely to have a job. The rate of employment among HIV/AIDS patients in this
      study was high however incomes were substantially lower than average. This could
      be due to low education levels or social stigma regarding these patients.
      Vocational education programs and public awareness could empower the patients
      economically. Similarly, a number of social and behavioral problems were
      associated with decreasing the working rate and productivity. Addressing these
      health issues may improve productivity among patients.

PMID- 30099884
TI  - Empathy Training Through Symptom Burden Simulation.
AB  - BACKGROUND: Providing quality care to hospice and palliative care patients
      requires the ability to feel and demonstrate empathic behaviors. To acquire a
      heightened level of empathy, the learner needs to internalize a process of
      experiencing first-hand real-life symptom burdens common at end of life. Making
      this happen during new employee orientation is a challenge but with powerful
      outcomes. OBJECTIVE: To increase empathy levels in hospice and palliative care
      staff within the agency. METHODS: A mandatory class for all new employees and
      open sessions for existing employees in a hospice and palliative care setting.
      Subjecting participants to multiple disease process simulations. RESULTS: All new
      employees participated in a symptom simulation workshop during their orientation.
      CONCLUSIONS: Ninety-eight percent of the new employees found their experience in
      the workshop to dramatically positively affect their empathy levels and
      consequently formulate compassionate responses to patient situations based on
      their experiences of feeling empathy during the training.

PMID- 30099885
TI  - Quality of life improvement, social stigma and antiretroviral treatment
      adherence: implications for long-term HIV/AIDS care.
AB  - By 2020, the Vietnamese government has committed to having 90% of patients
      receiving ART as well as 90% of those on ART having successful viral suppression.
      Factors that influence adherence to ART among patients are essential to allowing
      the adequate care. This study was conducted across 8 outpatient clinics in Hanoi
      and Nam Dinh province and included 1133 patients living with HIV. Socioeconomic
      factors such as marital status, education, employment as well as health-related
      quality of life improvements were investigated as potentially being associated
      with adherence rates of ART patients. Through multivariate logistic regression
      analysis with self-reported ART adherence and VAS scores, this study was able to
      identify marital status and employment as two factors associated with positive
      adherence scores. Similarly, health problems, stigmatization, and duration on ART
      were associated negatively with ART adherence. Knowing that these factors may be
      linked to adherence rates, they can be preemptively managed with patients to
      enhance adherence rates and achieve successful viral suppression.

PMID- 30099886
TI  - Abemaciclib: The Newest CDK4/6 Inhibitor for the Treatment of Breast Cancer.
AB  - OBJECTIVE: To review the pharmacology, efficacy, and safety of the cyclin
      dependent kinase (CDK) inhibitor, abemaciclib, in the treatment of advanced or
      metastatic breast cancer (MBC). DATA SOURCES: Relevant information was identified
      through a MEDLINE/PubMed (January 2000 to June 2018) literature search. The new
      drug application, prescribing information, and abstracts and posters from
      scientific meetings were also reviewed. STUDY SELECTION/DATA EXTRACTION: The
      literature search was limited to human studies published in the English language.
      Phase 1, 2, and 3 studies evaluating the pharmacology, efficacy, or safety of
      abemaciclib for breast cancer were included. DATA SYNTHESIS: Abemaciclib is an
      oral, potent, small molecule inhibitor of CDK4 and CDK6 activity, which blocks
      retinoblastoma tumor suppressor protein phosphorylation and thereby prevents
      progression through the cell cycle. Three major clinical trials, MONARCH 1, 2,
      and 3, established the efficacy and safety of abemaciclib for the treatment of
      hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)
      negative advanced or MBC. In these trials, response rates were promising, ranging
      from 19.7% to 59%, and median progression-free survival was significantly
      prolonged over the control arm in 2 of the trials. Common adverse effects
      included diarrhea, neutropenia, nausea, abdominal pain, infections, and fatigue.
      Relevance to Patient Care and Clinical Practice: Although no head-to-head studies
      have been completed between the CDK4/6 inhibitors, abemaciclib may be an
      attractive option because of its continuous dosing and ability to be used as
      monotherapy. CONCLUSIONS: Abemaciclib is an effective and well-tolerated
      treatment for HR-positive, HER2-negative advanced or metastatic breast cancer.

PMID- 30099887
TI  - Impact of a Medication Therapy Management Clinic on Glycosylated Hemoglobin,
      Blood Pressure, and Resource Utilization.
AB  - BACKGROUND: Medication therapy management is widely promoted to improve care.
      However, few well-controlled studies have evaluated its impact. OBJECTIVES: We
      evaluated whether enrollment in a comprehensive medication therapy management
      clinic (MTMC) was associated with improved 12-month outcomes. METHODS: This
      institutional review board approved study was a retrospective controlled cohort
      study in an academic health center serving low-income, African American and
      Latino populations. Between 2001 and 2011 MTMC patients were matched to control
      patients by age, gender, and comorbidities. Outcomes were mean change in
      glycosylated hemoglobin (A1C), diastolic (DBP) and systolic blood pressure (SBP),
      and emergency department (ED) and hospital admissions at 6 and 12 months. A
      difference-in-difference analysis was conducted for each outcome of interest,
      adjusting for observed, unmatched confounders. RESULTS: Patients with diabetes
      and receiving MTMC had greater A1C improvements, compared with controls, of 0.54%
      (P = 0.0067) at 6 months and 0.63% (P = 0.0160) at 12 months. At 6 months, SBP
      and DBP decreased in MTMC patients by 6.5 mm Hg (P = 0.0108) and 3.8 mm Hg (P =
      0.0136) more than controls, respectively. At 12 months, those receiving MTMC
      services had SBP and DBP decreases, respectively, of 8.2 mm Hg (P = 0.0018) and
      1.7 mm Hg (P = 0.2691) compared with controls. ED and hospital visits were not
      statistically significantly different between groups. Conclusion and Relevance:
      This MTMC potentially improved outcomes for referred patients in whom target
      goals were difficult to achieve and can serve as a model for other similar
      medication management programs.

PMID- 30099888
TI  - Clinical Safety Outcomes in Patients With Nonvalvular Atrial Fibrillation on
      Rivaroxaban and Diltiazem.
AB  - BACKGROUND: It is unknown whether diltiazem, a moderate cytochrome P450 enzyme
      (CYP3A4) and P-glycoprotein (P-gp) inhibitor, increases the incidence of bleeding
      events in combination with rivaroxaban, a CYP3A4 and P-gp substrate. OBJECTIVE:
      To assess major and clinically relevant nonmajor (CRNM) bleeding outcomes in
      patients with nonvalvular atrial fibrillation (NVAF) on rivaroxaban with
      concomitant diltiazem in a real-world setting. METHODS: This retrospective case
      cohort study included adult patients with NVAF prescribed both rivaroxaban and
      diltiazem for at least 30 days. Patients were matched 1:1 by age and baseline
      creatinine clearance (CrCl) to control patients taking rivaroxaban alone. The
      primary outcome was the composite of major and CRNM bleeding. Additional outcomes
      included bleeding events resulting in discontinuation of rivaroxaban, time to
      first bleeding event, and type of first bleed. RESULTS: A total of 143 cases and
      143 controls were included. The mean age was 69 years and median baseline CrCl
      was 87 mL/min. Median follow-up time was 12.4 months for cases and 16.5 months
      for controls. There was no significant difference in proportion of patients
      experiencing a major and/or CRNM bleeding event between cases and controls: 23.1%
      versus 28.0%, respectively; 9 cases and 8 controls permanently discontinued
      rivaroxaban because of bleeding. Gastrointestinal/rectal bleeding and hematuria
      were the most frequently reported bleeding events in both groups. Conclusion and
      Relevance: This is the first study to assess major and CRNM bleeding outcomes in
      patients with NVAF on rivaroxaban and diltiazem. Diltiazem use was not associated
      with an increased rate of bleeding events.

PMID- 30099889
TI  - Compatibility and safety of five lectin-binding putative probiotic strains for
      the development of a multi-strain protective culture for poultry.
AB  - The ban on the use of antibiotics as feed additives for animal growth promotion
      in the European Union and United States and the expectation of this trend to
      further expand to other countries in the short term have prompted a surge in
      probiotic research. Multi-species probiotics including safe and compatible
      strains with the ability to bind different nutritional lectins with detrimental
      effects on poultry nutrition could replace antibiotics as feed additives.
      Lactobacillus salivarius LET201, Lactobacillus reuteri LET210, Enterococcus
      faecium LET301, Propionibacterium acidipropionici LET103 and Bifidobacterium
      infantis CRL1395 have proved to be compatible as evaluated through three
      different approaches: the production and excretion of antimicrobial compounds,
      growth inhibition by competition for essential nutrients and physical contact,
      and a combination of both. The safety of P. acidipropionici LET103 was confirmed,
      since no expression of virulence factors or antibiotic resistance was detected.
      The innocuity of E. faecium LET301 should be further evaluated, since the
      presence of genes coding for certain virulence factors (gelE, efaAfm and efaAfs)
      was observed, albeit no expression of gelE was previously detected for this
      strain and there are no reports of involvement of efaAfm in animal pathogenicity.
      Finally, a combination of the five strains effectively protected intestinal
      epithelial cells of broilers from the cytotoxicity of mixtures of soybean
      agglutinin, wheat germ agglutinin and concanavalin A. To our knowledge, this is
      the first time that a combination of strains is evaluated for their protection
      against lectins that might be simultaneously present in poultry feeds.

PMID- 30099891
TI  - Effects of paraprobiotic Lactobacillus paracasei MCC1849 supplementation on
      symptoms of the common cold and mood states in healthy adults.
AB  - We investigated the effects of paraprobiotic Lactobacillus paracasei MCC1849 (LAC
      ShieldTM) on symptoms of the common cold and mood states in healthy young adults.
      A total of 241 participants were randomised to receive 1*1010 heat-killed L.
      paracasei MCC1849 cell powder (10LP), 3*1010 heat-killed L. paracasei MCC1849
      cell powder (30LP), or placebo powder without any L. paracasei cells once daily
      for 12 weeks based on the incidence of the common cold in the previous year, so
      that the risk of the incidence was equal among the groups. The incidence and
      severity of common cold symptoms were rated daily in a subject diary. Salivary
      secretory immunoglobulin A concentrations and saliva flow rates were analysed at
      0 and 6 weeks. The Profile of Mood States (POMS) was assessed using POMS 2 0, 6,
      and 12 weeks after the intervention. No significant differences were observed in
      the incidence of the common cold among the groups. In a prespecified subgroup of
      subjects who had the common cold in the previous year, the incidence, total
      number of days of symptoms, and symptom scores of the common cold significantly
      improved in the 10LP-intake group, and were slightly lower in the 30LP-intake
      group than in the placebo group. The level of deterioration in the positive mood
      state caused by stress was less in the MCC1849-intake group than in the placebo
      group. These results indicate that L. paracasei MCC1849 has the potential to
      improve resistance to common cold infections in susceptible subjects and maintain
      a desirable mood state, even under mental stress conditions. Further randomised
      controlled trials are needed in order to investigate the possible beneficial
      effects of paraprobiotic L. paracasei MCC1849 on the common cold in susceptible
      populations.

PMID- 30099890
TI  - Gut bacterial composition in a mouse model of Parkinson's disease.
AB  - The mechanism of neurodegeneration in Parkinson's disease (PD) remains unknown
      but it has been hypothesised that the intestinal tract could be an initiating and
      contributing factor to the neurodegenerative processes. In PD patients as well as
      in animal models for PD, alpha-synuclein-positive enteric neurons in the colon
      and evidence of colonic inflammation have been demonstrated. Moreover, several
      studies reported pro-inflammatory bacterial dysbiosis in PD patients. Here, we
      report for the first time significant changes in the composition of caecum
      mucosal associated and luminal microbiota and the associated metabolic pathways
      in a rotenone-induced mouse model for PD. The mouse model for PD, induced by the
      pesticide rotenone, is associated with an imbalance in the gut microbiota,
      characterised by a significant decrease in the relative abundance of the
      beneficial commensal bacteria genus Bifidobacterium. Overall, intestinal
      bacterial dysbiosis might play an important role in both the disruption of
      intestinal epithelial integrity and intestinal inflammation, which could lead or
      contribute to the observed alpha-synuclein aggregation and PD pathology in the
      intestine and central nervous system in the oral rotenone mouse model of PD.

PMID- 30099892
TI  - Probiotic Bacillus enhance the intestinal epithelial cell barrier and immune
      function of piglets.
AB  - Bacillus is widely used in the livestock industry. This study was designed to
      evaluate the effects of probiotic Bacillus amyloliquefaciens SC06 (Ba),
      originally isolated from soil, in piglets diet as an alternative to antibiotics
      (aureomycin), mainly on intestinal epithelial barrier and immune function. Ninety
      piglets were divided into three groups: G1 (containing 150 mg/kg aureomycin in
      the diet); G2 (containing 75 mg/kg aureomycin and 1*108 cfu/kg Ba in the diet);
      G3 (containing 2*108 cfu/kg Ba in the diet without any antibiotics). The results
      showed that, compared with the antibiotic group (G1), villus length, crypt depth
      and villus length/crypt depth ratio of intestine significantly increased in the
      G2 and G3 groups. In addition, intestinal villi morphology, goblet-cell number,
      mitochondria structure and tight junction proteins of intestinal epithelial cells
      in G2 and G3 were better than in G1. The relative gene expression of intestinal
      mucosal defensin-1, claudin3, claudin4, and human mucin-1 in G3 was significantly
      lower, while the expression of villin was significantly higher than in the
      antibiotic group. Probiotic Ba could significantly decrease serum interferon
      (IFN)-alpha, IFN-gamma, interleukin (IL)-1beta, and IL-4 levels, whereas increase
      tumour necrosis factor (TNF)-alpha and IL-6 secretion. Ba could also
      significantly decrease cytokines TNF-alpha, IFN-gamma, IL-1beta, and IL-4 level
      in liver, whereas it significantly increased IFN-alpha. Furthermore, replacing
      antibiotics with Ba also significantly down-regulated gene expression of TNF and
      IL-1alpha in intestinal mucosa, but up-regulated IL-6 and IL-8 transcription.
      Dietary addition of Ba could significantly reduce the gene expression of nuclear
      factor kappa beta (NFkappaB)-p50 and Toll-like receptor (TLR)6, while there was
      no significant difference for that of myeloid differentiation primary response
      88, TNF receptor-associated factor-6, nucleotide-binding oligomerisation domain
      containing protein 1, TLR2, TLR4, and TLR9. Taken together, our findings
      demonstrated that probiotic Ba could increase the intestinal epithelial cell
      barrier and immune function by improving intestinal mucosa structure, tight
      junctions and by activating the TLRs signalling pathway.

PMID- 30099894
TI  - The Art of Health Promotion: linking research to practice.

PMID- 30099893
TI  - Influence of monostrain and multistrain probiotics on immunity, intestinal
      ultrastructure and microbiota in experimental dysbiosis.
AB  - The biological effects of three probiotic strains Lactobacillus rhamnosus K32,
      Bifidobacterium longum GT15, Enterococcus faecium L3 and their mixture were
      studied using a model of dysbiosis induced in rats by antibiotics. It was found
      that after taking different probiotics intestinal microbiota changed in a strain
      specific manner. The maximal activity against pathogens was revealed after the
      administration of a mixture of bacterial strains under study or a single strain
      of enterococci. The strain E. faecium L3 showed the most activity against both
      Klebsiella spp. and Bacteroides fragilis. It helped to restore the original
      content of Faecalibacterium prausnitzii. The number of Klebsiella spp. was the
      same in the group receiving L. rhamnosus K32 and the group of animals, which was
      not consuming probiotics. Different probiotic strains included in the composition
      had various immunological effects. Probiotic bifidobacteria, enterococci and the
      mixture of three probiotics stimulated of mRNA expression of interleukin (IL)-10
      in mesenteric lymph nodes. The changes in microbiota after consuming an
      enterococcal probiotic correlated with an increase in transforming growth factor
      (TGF)-beta and IL-10 content in blood serum and an increase of the intestinal
      mucus layer. Consumption of L. rhamnosus K32 led to the stimulation of IL-8
      expression in mesenteric lymph nodes. Control group not receiving probiotics was
      characterised by expression of pro-inflammatory cytokines, damage of epithelial
      cells and the destruction of their tight junctions. The damage to the
      ultrastructure of the mucosa was prevented in all the groups taking probiotics.

PMID- 30099896
TI  - Sleep Deprivation and the Workplace: Prevalence, Impact, and Solutions.

PMID- 30099895
TI  - Is Health Promotion a Journey or a Destination?
AB  - Recent data on our progress in workplace-based health promotion should keep us
      grounded as we consider whether we are on track to planned destinations. One
      recent survey suggests employees view worksite wellness as a valuable employee
      benefit but another survey suggests employees are dissatisfied with their
      employers' wellness offerings. What explains these differences? Is the program
      driven by a plan? Is the plan relevant to the company's priorities? Was the plan
      developed using participatory planning principles?" A participant centered health
      promotion initiative means deciding a destination and planning how to get there
      alongside those you aspire to serve. This approach is far more likely to lead to
      alternative routes and, often, untested sources of data for finding the way. The
      urgent opportunity for workplace-based program planners is that of strategic
      planning that is guided by a continuous review of credible metrics such as those
      offered in best practices scorecards.

PMID- 30099897
TI  - Sleep at Work: The Economic and Societal Argument for Workplace-Based Health
      Promotion Tailored to Shift Workers.

PMID- 30099898
TI  - Sleep: An Integral Component of Employee Well-Being Programs.

PMID- 30099899
TI  - Everyone Sleeps!-(Poorly) or Not Enough: Sleep as a Priority and Vital Sign.

PMID- 30099900
TI  - The Cost of Sleep Lost: Implications for Health, Performance, and the Bottom
      Line.

PMID- 30099901
TI  - In Briefs.

PMID- 30099903
TI  - [Pernicious anemia in a thalassemic patient - difficulties of the diagnosis].
AB  - The bone marrow aspiration, which was done in a leukopenic, hypochromic,
      microcytic, progressive anemic, thalassemic patient, revealed megaloblastic
      morphology. The low level of vitamin B12 and the reticulocytosis following the
      B12 supportation strenghtened the diagnosis of pernicious anemia. The set of the
      right diagnosis has been delayed by the fact that even in severe anemia one could
      not obtain the typical signs of B12 deficiency, having a hypochromic, microcytic
      erythrocyte morphology, due to the thalassemia minor disorder. Orv Hetil. 2018;
      159(33): 1368-1371.

PMID- 30099904
TI  - [Diabetes mellitus: endothelial dysfunction and changes in hemostasis].
AB  - Diabetes mellitus involves a group of chronic metabolic disorders with elevated
      blood glucose concentrations. Since this disease needs lifelong treatment and
      care, the medical and social aspects present major public health concerns and
      pose a global challenge for health care providers. The number of aged patients
      with degenerative diseases undergoing surgical procedures is continuously
      increasing, resulting in an overwhelming dominance of diabetes in the
      perioperative care. There is a particular need for an increased awareness of
      diabetic patients in cardiovascular units, where the incidence of this disease
      reaches as high as 30-40%. The main hallmarks of the pathologic metabolic milieu
      of diabetes are hyperglycaemia, insulin resistance and pathologic lipid
      metabolism. The biochemical, cellular and organ-level pathophysiological changes
      lead to endothelial dysfunction including a low-grade prothrombotic balance,
      inflammatory state and, as a consequence, impaired micro- and macrocirculation.
      Diabetes is also followed by platelet dysfunction resulting from intracellular
      hyperglycaemia, because thrombocytes have insulin-independent glucose
      transporters in their cell membrane. The levels of the coagulation factors of the
      plasma are increased, and these factors are also modified by oxidation and
      glycation. Diabetes mellitus is a prothrombotic condition resulting from direct
      and indirect tendencies of the endothelial platelet and the plasma coagulation
      factors. The basic "bench to clinical basics" knowledge of the endothelial
      dysfunction and prothrombotic balance in diabetes may contribute to the better
      understanding of the clinical focuses in the perioperative care of patients with
      diabetes mellitus. Orv Hetil. 2018; 159(33): 1335-1345.

PMID- 30099906
TI  - [Cardiac rehabilitation and its sporty face].
AB  - The prognosis of cardiac and other diseases is highly determined by the level of
      cardiopulmonary fitness (aerobic capacity). The main purposes of rehabilitative
      activities include the restoration and increase of VO2max. The "classic" method
      is the continuous aerobic exercise (moderate-intensity continuous exercise). The
      higher increase of aerobic capacity in a shorter time can be developed by
      interval loads: shorter or longer active periods are interspersed by low
      intensity rest periods. A recent form is the high-intensity interval training:
      0.5-4 minutes on 70-90% of the aerobic capacity followed by a rest or low
      intensity biking/walking/jogging/any activity. The sprint interval training uses
      a few ten seconds of maximal intensity bursts changed with longer low-intensity
      activities. The advantages of the interval methods are shorter training time,
      less monotony, higher efficiency with not more risks. Interval training methods
      are applied also in other pathologies without disadvantages. Orv Hetil. 2018;
      159(33): 1346-1352.

PMID- 30099905
TI  - [Personnel and material conditions of the Hungarian intensive care units dealing
      with organ donation].
AB  - INTRODUCTION: At the end of 2016, the number of patients on the domestic
      transplant waiting list was twice as much as the number of the organ
      transplantations accomplished that year. The institutional prerequisites for
      functional organ donation programs are the sufficient number of personnel and the
      adequate material conditions to be provided in relation to the needs. AIM: The
      goal of the current study was to evaluate the professional environment in
      Hungary. METHOD: The Organ Coordination Office at the Hungarian National Blood
      Transfusion Service compiled a questionnaire survey on the personnel and material
      conditions of the intensive care units (ICUs) in Hungary in regards to organ
      donations. The survey applied an online questionnaire including 43 questions. In
      addition to the number of beds and employees, we investigated the tools needed
      for the legal and the medical diagnosis of brain death as well as the
      accessibility of examinations on the donor information form. The data collection
      spanned from 12 December 2016 to 30 June 2017. RESULTS: 59 intensive care units
      completed the questionnaire; the investigation involved 640 hospital beds, 816
      physicians and 1252 nurses. In the daytime shift, 0.25 doctors and 0.41 nurses
      work on a patient bed at an average, while in the night shift, the figures are
      0.11 and 0.33, respectively. 51.7% of the doctors are registered to access the
      National Non-Donor Registry, and brain death diagnosis committee is available in
      83% of the hospitals. Among the medical imaging methods (cranial, abdominal
      thoracic), CT scan in 71-73%, abdominal ultrasound in 75%, transthoracic
      echocardiograpy (TTE) in 37%, transoesophageal echocardiography (TEE) in 4%,
      bronchoscopy in 49%, coronarography in 19% are non-stop available, with instant
      interpretation in 75% of the cases. Transcranial Doppler (TCD) in 30%, four
      vessel angiography in 45% and SPECT in 14% of the cases are available. More than
      90% of the laboratory examinations on the donor information form are available 24
      hours a day. CONCLUSION: The number of doctors and nurses did not change compared
      to our 2008 survey (0.18 doctors, 0.37 nurses/ICU beds in 2008), but the care of
      potential donors needs more resources and time. The standby availability of
      personnel and material conditions is a prerequisite for organ donation programs
      in order to save lives. Orv Hetil. 2018; 159(33): 1360-1367.

PMID- 30099908
TI  - Senile-Onset Subacute Sclerosing Panencephalitis, Presenting With Peculiar
      Findings.
AB  - Subacute sclerosing panencephalitis (SSPE) is a well-known childhood disease;
      however, the adult onset of SSPE cases are also widely recognized where the
      oldest case reported is 52 years old. We report a 61-year-old woman patient
      presenting with atypical clinical and EEG features, diagnosed with SSPE. Measles
      and SSPE have decreased dramatically owing to worldwide immunization programs;
      however, there are still reasons to consider SSPE in differential diagnosis even
      in patients presenting with atypical clinical findings and older ages. First,
      there is a generation who missed the immunization era, constituting a latent
      disease pool. Second, antivaccination movements have led to a decline in MMR
      (measles, mumps, rubella) vaccination worldwide, leading to measles outbreaks and
      potential future SSPE cases. Third, most of the vaccination programs start
      measles immunization at the age of 12 months, leading to a shift in the incidence
      below the age of 1 year, when the risk of developing SSPE in adult life is
      higher. Finally, disruption in vaccination programs, in which fast disease
      transmission due to close contact living, unhygienic conditions of refugee camps,
      and limited access to health care in displaced populations have also led to
      measles outbreaks. In conclusion, we believe that neurologists for adults should
      consider SSPE in differential diagnosis, even in older patients with atypical
      presentations.

PMID- 30099907
TI  - [Phagocytic function of monocytes and neutrophil granulocytes in ovarian cancer].
AB  - INTRODUCTION: Recently, tumor-infiltrating immune cells have been studied in
      various cancers. However, fewer studies address the role of peripheral immune
      cells in the pathogenesis of cancer. AIM: Our aim was to investigate whether the
      phagocytic activity of peripheral monocytes and neutrophil granulocytes is
      affected by the removal of tumor in advanced ovarian cancer. METHOD: We
      investigated peripheral blood samples from 12 patients with advanced stage of
      serous epithelial ovarian cancer - which were collected before the optimal tumor
      reduction surgery and on the 7th postoperative day - and from 8 healthy women.
      After separation of monocytes and neutrophils, the cells were incubated with
      opsonized fluorescein isothiocyanate-labeled zymosan A particles as the target of
      phagocytosis. By using fluorescence microscope we counted the number of particles
      phagocytized by the cells and calculated the phagocytic index. Statistical
      analysis of the data was performed using analysis of variances method. RESULTS:
      Preoperative phagocytic indexes of monocytes and neutrophils from patients were
      significantly lower than phagocytic indexes of the corresponding cells from
      healthy women. The phagocytic function of monocytes and granulocytes isolated
      from postoperative samples of patients significantly increased compared to
      preoperative values and reached the phagocytic indexes of monocytes and
      neutrophils from healthy controls. CONCLUSION: Based on our results we assume
      that the tumor and/or its microenvironment in ovarian cancer may produce factors
      that can depress the phagocytic function of monocytes and granulocytes. Since the
      phagocytic indexes increased following the cytoreductive surgery, it can be
      assumed that after the removal of the tumor, the production of these factors is
      reduced or eliminated. Orv Hetil. 2018; 159(33): 1353-1359.

PMID- 30099909
TI  - Interactions between tumor-associated macrophages and tumor cells in
      glioblastoma: unraveling promising targeted therapies.
AB  - INTRODUCTION: Glioblastoma (GBM) is the deadliest primary malignant central
      nervous system (CNS) tumor with a median overall survival of 15 months despite a
      very intensive therapeutic regimen including maximal safe surgery, radiotherapy,
      and chemotherapy. Therefore, GBM treatment still raises major biological and
      therapeutic challenges. Areas covered: One of the hallmarks of the GBM is its
      tumor microenvironment including tumor-associated macrophages (TAM). TAM,
      accounting for approximately 30% of the GBM bulk cell population, may explain, at
      least in part, the immunosuppressive features of GBMs. The TAM are active and
      highly plastic immune cells and include two major ontogenetically different cell
      populations: (i) microglia and, (ii) monocytes-derived macrophages (MDM). TAM
      recruited to the tumor bulk can be reprogramed by GBM cells resulting in an
      ineffective anti-tumor response. Interestingly, interactions between TAM and GBM
      cells promote tumor oncogenesis (i.e. tumor cells proliferation and
      migration/invasion). This review aims to explore TAM targeting in GBM as a
      promising therapeutic option in the near future. Expert Commentary: A better
      understanding of TAM-GBM interactions and dynamics will certainly uncover new
      anti-GBM therapeutic avenues.

PMID- 30099910
TI  - Accuracy of sonographic estimated fetal weight in suspected macrosomia: the
      likelihood of overestimating and underestimating the true birthweight.
AB  - OBJECTIVE: Macrosomia has increased risk of serious adverse outcomes for both
      infants and their mothers. As such, many providers recommend induction of labor
      or cesarean delivery (CD) based on sonographic estimated fetal weight (sonoEFW)
      cutoffs. It is known that sonoEFW is a poor predictor of birthweight (BW),
      especially at the extremes of weight. It is not clear, however, whether sonoEFWs
      tend to underestimate or overestimate the true BW among fetuses with suspected
      macrosomia. The objective of this study was to compare rates of overestimation of
      BW among women with suspected macrosomia by sonoEFW. METHODS: This was a
      retrospective cohort study of women who presented to a single maternal-fetal
      medicine ultrasound unit within 2 weeks prior to delivery from January 2011 to
      November 2017. We identified women who received a sonoEFW >=4000 g. The study
      sample was divided into four sonoEFW categories: 4000-4249, 4250-4499, 4500-4749,
      and >=4750 g. Accuracy of sonoEFW was compared across groups, with the primary
      outcome being overestimation of BW. RESULTS: A total of 502 patients were
      included, of whom 301 (60.1%) had a sonoEFW 4000-4249 g, 135 (26.9%) had a
      sonoEFW 4250-4499 g, 45 (9.0%) had a sonoEFW 4500-4749 g, and 21 (4.2%) had a
      sonoEFW >=4750 g. In each sonoEFW group, the risk of overestimating BW was
      greater than 50%, and the likelihood of overestimation of BW increased
      significantly across sonoEFW groups (69.4, 76.3, 80.0, 95.2%, p < .001). This
      held true after adjusting for differences in baseline characteristics, including
      diabetes and amniotic fluid index. BW >=4500 g was not accurately predicted.
      Among women with sonoEFW 4500-4749 g, only 28.9% delivered a neonate with a BW
      >4500 g; for women with a sonoEFW >=4750 g, only 47.6% had a BW >4500 g. One
      hundred sixty-one (32.1%) women underwent CD for suspected macrosomia. Of these
      CDs, 48 (29.8%) of neonates had a BW <4000 g and 134 (83.2%) had a BW <4500 g.
      CONCLUSION: In patients undergoing sonoEFW within 2 weeks of delivery, sonoEFWs
      >=4000 g are significantly more likely to overestimate than underestimate the
      true BW. Obstetricians should be cautious about intervening based on sonoEFW
      alone, given the high risk that this value is an overestimation of the true
      weight.

PMID- 30099911
TI  - Cardiovascular impact of testosterone therapy for hypogonadism.
AB  - INTRODUCTION: Since 2010 some evidence supporting the possible increased
      cardiovascular (CV) risk related to testosterone treatment (TTh) has created much
      debate in the scientific community. Based on these results, the US Food and Drug
      Administration agency has questioned TTh for aging men recognizing its value only
      for classical hypogonadism due to genetic or organic causes. To better clarify
      this topic, we scrutinized and summarized, also by using meta-analytic methods,
      the data generated during the last 7 years, as derived from the analysis of
      randomized controlled trials (RCTs) on TTh and CV risk. Areas covered: Analysis
      included 31 RCTs published between 2010 and 2018. Retrieved trials included 2675
      and 2308 patients in TTh and placebo groups, respectively. The analysis
      documented that TTh was not associated with an increased CV mortality or
      morbidity either when overall or major adverse CV events were considered. Expert
      commentary: Despite present evidence it is important to recognize that the
      duration of the available trials is short (lower that 3 years) limiting final
      conclusions on this topic. In particular, the available information on possible
      long-term effects of TTh on CV risk is limited. Long-term safety studies are
      advisable to better clarify these points.

PMID- 30099912
TI  - Biomarkers of drug-induced acute kidney injury: a regulatory perspective.
AB  - INTRODUCTION: Biomarkers are one of the drug development tools that are being
      developed through collaborative efforts among multiple stakeholder communities to
      enhance the drug development process. Biomarkers of acute drug-induced renal
      injury as used in drug development are more commonly referred to as renal safety
      biomarkers, the focus of this manuscript. Areas covered: This manuscript provides
      an overview of the history and evolution of the United States Food and Drug
      Administration's Center for Drug Evaluation and Research's Biomarker
      Qualification Program. In addition, a regulatory perspective on the potential for
      renal safety biomarkers to accelerate medical and pharmaceutical research is
      presented. The first qualification submissions (acute kidney injury biomarkers)
      are discussed, including how the FDA review process affected the evolution of the
      biomarker qualification process and the future of biomarker discovery,
      development, and use. This manuscript also discusses a new repository for data on
      novel translational safety biomarkers from drug development programs. Expert
      opinion: In addition to the qualification of novel biomarkers, a key achievement
      of the first submission for qualification was the bringing together of multiple
      stakeholder communities to optimize the process. Early qualification reviews
      provided valuable lessons that informed an overarching approach of how to develop
      a biomarker for regulatory use.

PMID- 30099913
TI  - A review of factors associated with severe violence in schizophrenia.
AB  - BACKGROUND: There is a modest but consistent association between violence and
      schizophrenia. The consequences of serious violence could be catastrophic for the
      victims, as well as the patients themselves and the community. Any knowledge that
      would help to prevent acts of serious violence would be of considerable value for
      the individual and the society. AIM: To identify external and clinical risk
      factors for serious violence in schizophrenia, in addition to considering the
      strength of the association between the factors assessed and severe violence.
      METHODS: This was accomplished by a literature survey. One-hundred and two
      relevant papers were identified that were published during the past 20 years.
      Forty-four papers were assessed for eligibility. In all, 27 studies including
      clinical or cognitive variables were reviewed systematically. An effect size was
      reported where an odds ratio (OR) could be identified or calculated from
      available data. Five external factors and six clinical domains were evaluated.
      RESULTS: Substance abuse is robustly linking schizophrenia and violence. Among
      the clinical factors, insight, impulsivity, psychopathy, motor speed and a global
      measure of cognition are the factors with the strongest empirical evidence for an
      association with severe violence. CONCLUSION: This is the first systematic review
      of risk factors for severe violence in schizophrenia, in which a great number of
      clinical and external factors have been evaluated. Most of the clinical factors
      have been compared on effect size. The identified factors that represent an
      increased risk of violence in patients with schizophrenia should be included in
      risk assessments.

PMID- 30099914
TI  - Laryngoscopes for difficult airway scenarios: a comparison of the available
      devices.
AB  - INTRODUCTION: According to the American Society of Anesthesiologists, the
      incidence of difficult intubation in the operating room is 1.2-3.8%; however, in
      emergency conditions, this rate is higher and reaches even 5.3%. Successful
      emergency airway management is an essential component of the modern practice of
      medicine. Areas covered: The aim of the study is to review the literature
      regarding different devices used to perform endotracheal intubation (Macintosh,
      Miller, and McCoy laryngoscopes; ETView, GlideScope, TruView, Airtraq, McGrath
      MAC, Pentax AWS, Trachlight, Shikani, and Bullard) and discuss their clinical and
      experimental role in difficult airway management. Expert commentary: Owing to the
      development of medical technology, there are an increasing number of
      videolaryngoscopes and other devices facilitating endotracheal intubation in
      difficult airway scenarios, including cardiopulmonary resuscitation, cervical
      spine injury, or face-to-face intubation. Each of these devices may bring
      benefits in the form of increasing the intubation effectiveness, as well as
      shortening the procedure, provided that the person performing intubation is
      familiar with the use of the device.

PMID- 30099915
TI  - Immunobiology of periprosthetic inflammation and pain following ultra-high
      molecular-weight-polyethylene wear debris in the lumbar spine.
AB  - INTRODUCTION: Wear debris-induced osteolysis is a common cause of arthroplasty
      failure in several joints including the knee, hip and intervertebral disc. Debris
      from the prosthesis can trigger an inflammatory response that leads to aseptic
      loosening and prosthesis failure. In the spine, periprosthetic pain also occurs
      following accumulation of wear debris through neovascularization of the disc. The
      role of the immune system in the pathobiology of periprosthetic osteolysis of
      joint replacements is debatable. Areas covered: We discussed the stimulation of
      pro-inflammatory and pro-protective and pro-regenerative pathways due to debris
      from the prosthetics. The balance between the two pathways may determine the
      outcome results. Also, the role of cytokines and immune cells in periprosthetic
      inflammation in the etiology of osteolysis is critically reviewed. Expert
      commentary: Therapies targeting the inflammatory process associated with ultra
      high-molecular-weight polyethylene wear debris could reduce implant failure.
      Additionally, therapies targeting neovascularization of discs following
      arthroplasty could mitigate periprosthetic pain.

PMID- 30099916
TI  - The role of racial/ethnic factors in global clinical trials.

PMID- 30099917
TI  - Evaluating Nasalance Values Among Bilingual Mandarin-English Speakers.
AB  - OBJECTIVE: The goals of this research are (1) to establish normative nasalance
      values for bilingual Mandarin-English speakers and compare values to those of
      previously reported monolingual Mandarin speakers, and (2) to examine whether
      sex, age, dialect, and language proficiency affect levels of nasalance among
      Mandarin-English speakers in both English and Mandarin. DESIGN: All participants
      recorded the speech stimuli, constructed to include oral sentences, nasal
      sentences, oronasal sentences, and vowels /alpha, i, u/ in Mandarin and English.
      Nasalance measurements were recorded using the Nasometer II 6450. PARTICIPANTS
      AND SETTING: A total of 45 (20 males and 25 females) native Mandarin speakers
      between 20 and 54 years of age from mainland China participated in the study.
      RESULTS: Mean nasalance scores of the Mandarin oral sentence (Mean [M] = 17.64,
      standard deviation [SD] = 7.33), oronasal sentence (M = 54.62, SD = 7.81), and
      nasal sentence (M = 68.73, SD = 8.09) are reported. Mean nasalance scores of the
      English oral sentence (M = 20.02, SD = 7.83), oronasal sentence (M = 58.71, SD =
      7.59), and nasal sentence (M = 65.27, SD = 7.45) are reported. A repeated
      measures analysis of variance showed significant sex difference in nasalance
      scores for English stimuli ( P = .031) and Mandarin stimuli ( P = .040). There
      was no significant effects of age, dialect, and language proficiency on Mandarin
      or English stimuli. CONCLUSIONS: This is the first study to report normative
      values for Mandarin-English speakers using the Nasometer II. Values reported can
      be used for objective assessment of bilingual speakers.

PMID- 30099918
TI  - Cardiac sarcoidosis - an expert review for the chest physician.
AB  - INTRODUCTION: Sarcoidosis is a multisystem granulomatous disease predominantly
      affecting the lungs, with increased risk of cardiovascular disease, pulmonary
      hypertension and cardiac sarcoidosis (CS), the latter due to direct granuloma
      infiltration. Sarcoidosis is often managed by chest physicians who need to
      understand the diagnostic pathways and initial management plans for patients with
      cardiac involvement. Areas covered: The most serious consequence of CS is sudden
      cardiac death due to ventricular tachyarrhythmias or complete atrioventricular
      block. Additional complications include atrial arrhythmias and congestive cardiac
      failure. There are no internationally accepted screening pathways, but a
      combination of history, clinical examination and ECG detects up to 85% of cases.
      Newer modalities including signal-averaged ECG and speckle-tracking
      echocardiography increase identification of patients who require a definitive
      diagnosis. Early immunosuppression reduces the risk of conduction abnormalities
      and incidence of supraventricular arrhythmias. Management of ventricular
      arrhythmias requires antiarrhythmic medications followed by possible catheter
      ablation and device (ICD) implantation. Expert commentary: Prospective trials are
      underway to identify the optimum methods for screening, which will guide future
      international statements on indications for and methods of screening in CS.

PMID- 30099920
TI  - Genetic Polymorphism of VKORC1-1639 in Children With Intracranial Hemorrhage Due
      to Vitamin K Deficiency.
AB  - Intracranial hemorrhage due to vitamin K deficiency is a serious disease that can
      lead to morbidity, mortality, and mental retardation. Our goal in this study is
      to determine the frequency of VKORC1-1639 G>A polymorphism in patients who have
      undergone intracranial hemorrhage due to vitamin K deficiency bleeding (VKDB). To
      study VKORC1-1639 G>A polymorphism, blood was drawn from patients (n = 51, age
      8:0 +/- 6:5 years) followed at the Pediatric Neurology and Hematology section,
      Faculty of Medicine, Erciyes University, between 1990 and 2016, diagnosed with
      VKDB as idiopathic or from patients diagnosed with intracranial hemorrhage due to
      secondary vitamin K deficiency and also from volunteers (n = 51, age 11 +/- 4.5
      years). Intensive care and nutrition needs of patients and the laboratory
      radiological imaging results and treatments that were applied were analyzed
      through scanning the files of the patients and information received from
      families. Through detailed physical examination, patients with neurologic
      sequelae and ongoing epilepsy were determined. The results were compared to
      clinical and laboratory results with control group. Eight (15.7%) of the patients
      were normal, 29 (56.9%) heterozygous carrier, and 14 (27.5%) homozygous mutants.
      In the control group, 19 (37.3%) were normal, 19 (37.3%) heterozygous carriers,
      and 13 (25.5%) homozygous mutants. The VKOR1-1639>A (SNP:rs9923231) mutant
      positivity (homozygous plus heterozygous mutant) was significantly higher in the
      patient group when compared to controls. There were no significant differences
      between patient and control groups in terms of the prognosis.

PMID- 30099921
TI  - Correlates of recent HIV infection among men who have sex with men recruited
      through the internet in Huzhou City, Eastern China.
AB  - Objective To identify factors associated with recent HIV infection among men who
      have sex with men (MSM) in Huzhou City, Eastern China, who seek sexual partners
      via the internet. Methods Adult members of Tencent QQ instant messaging software,
      who completed a face-to-face interview questionnaire and serological HIV testing
      at baseline, were enrolled into this prospective cohort study. Questionnaires and
      serological testing were also completed at 6 and 12 months. Cox proportional
      hazards was used for initial bivariate analyses of differences between
      participants with or without recent HIV infection, and for subsequent forward
      stepwise multiple regression of statistically significant variables. Results Out
      of 415 baseline participants, 283 completed the 12-month follow-up (25 with
      recent HIV infection and 258 without; recent HIV infection rate, 8.20 per 100
      person-years). Recent HIV infection was shown to be significantly associated with
      <= high school education (versus college/university), registered residence
      outside Huzhou City (versus within Huzhou City), having >= two male sexual
      partners, and syphilis infection. Conclusions Improving education levels,
      treating syphilis promptly, and reducing the number of male sexual partners may
      reduce HIV transmission among MSM in Eastern China.

PMID- 30099919
TI  - Development of rapid and simple experimental and in silico serotyping systems for
      Citrobacter.
AB  - AIM: Members of the genus Citrobacter are important opportunistic pathogens
      responsible for high mortality rate. Therefore, in this study, we aimed to
      develop efficient and accurate Citrobacter typing schemes for clinical detection
      and epidemiological surveillance. MATERIALS & METHODS: Using genomic and
      experimental analyses, we located the O-antigen biosynthesis gene clusters in
      Citrobacter genome for the first time, and used comparative genomic analyses to
      reveal the specific genes in different Citrobacter serotypes. RESULTS: Based on
      the specific genes in O-antigen biosynthesis gene clusters of Citrobacter, we
      established experimental and in silico serotyping systems for this bacterium.
      CONCLUSION: Both serotyping tools are reliable, and our observations are
      biologically and clinically relevant for understanding and managing Citrobacter
      infection.

PMID- 30099922
TI  - Impact of Time to Start Systemic Therapy on the Outcomes of Patients with
      Metastatic Colorectal Cancer Treated with First Line FOLFOX Chemotherapy; a
      Patient-Level Pooled Analysis of Two Clinical Trials.
AB  - BACKGROUND: Impact of time to start first-line systemic chemotherapy following
      diagnosis of metastatic colorectal cancer (mCRC) needs to be studied. METHODS:
      This is a pooled analysis of the raw data of the comparator arms of two
      randomized studies (NCT00272051; NCT00305188). Univariate and multivariate
      analyses of predictors of overall and progression-free survival were conducted
      through Cox regression analysis. Factors with statistically significant P value
      (P < 0.05) in the univariate part of the analysis were included in the
      multivariate analysis. RESULTS: In univariate analysis, time to start systemic
      therapy did not affect overall or progression-free survival (P=0.694; P= 0.891
      respectively). In multivariate analysis for overall survival, the following
      factors were predictive of worse overall survival: younger age (P = 0.019),
      higher ECOG performance score (P = 0.001), more than one site of metastatic
      disease (P = 0.002), colon site of the primary tumor (P = 0.004), and no
      oncologic surgery to the primary tumor (P < 0.001). Likewise, in multivariate
      analysis for progression-free survival, the following factors were predictive of
      worse progression-free survival: no oncologic surgery to the primary (P < 0.001),
      more than one organ of metastatic disease (P < 0.001), and no concurrent
      bevacizumab administration (P = 0.015). CONCLUSION: Time to start systemic
      chemotherapy does not appear to impact overall or progression-free survival among
      mCRC patients.

PMID- 30099923
TI  - Strengthening Nutrition-Specific Policies for Adolescents in Indonesia: A
      Qualitative Policy Analysis.
AB  - BACKGROUND: There is a growing recognition of the importance of adolescent health
      and well-being. Yet, little attention has been paid to adolescent nutrition, and
      few policies and programs are targeting to improve adolescent nutrition in
      Indonesia. OBJECTIVE: This analysis aimed to identify (1) the extent to which
      adolescents are considered in nutrition policy in Indonesia and (2) opportunities
      to improve nutrition policy content to effectively target adolescents. METHODS:
      We collected data on policy content through a desk review of national and
      subnational level nutrition-specific strategic plans, laws, regulations, and
      program guidelines. We then conducted 74 key informant interviews with policy
      makers and program experts in health, education, and related sectors using
      semistructured interview guides based on policy theory to examine policy context
      and implementation. The policy content and interview data were analyzed using
      thematic synthesis and narrative analysis. RESULTS: Currently, 2 nutrition
      specific policies and programs are designed to improve adolescent nutrition in
      Indonesia, one focusing on iron-folic acid supplementation for adolescent girls
      and another on obesity prevention and management in schools. These programs are
      yet to be implemented at scale. Overall, adolescent nutrition is not yet
      considered a priority in the national development agenda. An opportunity exists
      to improve action on adolescent nutrition in Indonesia through scaling up of
      district-level policies and through improving coordination mechanisms across
      sectors. CONCLUSIONS: Few policies and programs exist to support adolescent
      nutrition in Indonesia. Coordinated efforts across relevant sectors and levels of
      government should be made to mainstream adolescent nutrition into relevant
      policies.

PMID- 30099924
TI  - Cost consequence analysis of use of a balloon expandable vascular access system
      and standard vascular sheath for transcatheter aortic valve implantation.
AB  - BACKGROUND: Vascular complications are an important complication of transcatheter
      aortic valve implantation and are associated with increased morbidity and
      mortality as well as cost. The Solopath device is an expandable vascular access
      system that has previously been shown to be associated with lower rates of
      vascular complications. This study sought to evaluate the impact of the use of
      this system on vascular complications and costs in a decision model analysis.
      METHODS: A cost-consequence analysis was undertaken utilizing event rate data
      from the PARTNER trials and a published retrospective analysis of the Solopath
      device. The decision model estimated costs and benefits in a hypothetical cohort
      of patients with aortic stenosis undergoing TAVI using either a standard sheath
      or Solopath. The modeled analysis compared the occurrence of vascular
      complications and mortality at 30 days and 1 year using TreeAge Pro. RESULTS: The
      decision model demonstrated that use of the Solopath sheath resulted in 36 fewer
      major vascular complications, three fewer deaths at 30 days, and five fewer
      deaths at 1 year, resulting in a discounted cost savings of $846 CDN. Results
      were sensitive to decreasing rates of vascular complications with newer
      generation devices, however maintained modest cost-savings. CONCLUSIONS:
      Reduction in vascular complications is an important part of improving care for
      TAVI patients. The Solopath vascular access device offers an alternative to
      standard sheaths with a potential reduction in complications and cost-savings.

PMID- 30099925
TI  - Current challenges in managing comorbid heart failure and COPD.
AB  - INTRODUCTION: Heart failure (HF) with reduced ejection fraction and chronic
      obstructive pulmonary disease (COPD) frequently coexist, particularly in the
      elderly. Given their rising prevalence and the contemporary trend to longer life
      expectancy, overlapping HF-COPD will become a major cause of morbidity and
      mortality in the next decade. Areas covered: Drawing on current clinical and
      physiological constructs, the consequences of negative cardiopulmonary
      interactions on the interpretation of pulmonary function and cardiopulmonary
      exercise tests in HF-COPD are discussed. Although those interactions may create
      challenges for the diagnosis and assessment of disease stability, they provide a
      valuable conceptual framework to rationalize HF-COPD treatment. The impact of
      COPD or HF on the pharmacological treatment of HF or COPD, respectively, is then
      comprehensively discussed. Authors finalize by outlining how the non
      pharmacological treatment (i.e. rehabilitation and exercise reconditioning) can
      be tailored to the specific needs of patients with HF-COPD. Expert commentary:
      Randomized clinical trials testing the efficacy and safety of new medications for
      HF or COPD should include a sizeable fraction of patients with these coexistent
      pathologies. Multidisciplinary clinics involving cardiologists and respirologists
      trained in both diseases (with access to unified cardiorespiratory rehabilitation
      programs) are paramount to decrease the humanitarian and social burden of HF
      COPD.

PMID- 30099926
TI  - Pancreatic cancer circulating tumor cells: applications for personalized
      oncology.
AB  - INTRODUCTION: Pancreatic cancer (PC) is a highly lethal disease, in part because
      of early metastasis, late diagnosis, and limited treatment options. Circulating
      tumor cells (CTCs) are cancer cells that have achieved the metastatic step of
      intravasation, and are thus a unique source of biomarkers with potential
      applications in the staging, prognostication, and treatment of PC. Areas covered:
      This review describes the use of CTCs in PC, including isolation methods, the
      significance of CTC enumeration, and studies examining phenotypic and molecular
      characteristics of CTCs. We also speculate on future directions for PC CTC
      research such as single-cell analysis and CTC culture. Expert commentary: CTCs
      represent a potential unique serial source of cancer tissue via a convenient and
      minimally invasive blood draw. Recent development of isolation methods that allow
      for the release of viable CTCs with unaltered molecular characteristics has set
      the stage for single-cell analysis and ex vivo culture. Although there is
      significant potential for CTCs as a biomarker to impact PC from diagnosis to
      therapy, there still remain a number of challenges to the routine implementation
      of CTCs in the clinical management of PC.

PMID- 30099927
TI  - The Romanian Adaptation of the Survey Work-Home Interaction, NijmeGen.
AB  - To date, there are no scales measuring work-home interaction which are adapted
      for the Eastern European population. Owing to the significantly different
      sociocultural contexts and geopolitical history between Western and Eastern
      populations, despite the massive contemporary East-West migration, a more
      culturally appropriate scale is needed to ensure valid and reliable measurement
      of the construct. This article presents the adaptation of the Survey Work-Home
      Interaction-NijmeGen (SWING) for the Romanian population. The results show that
      SWING can successfully measure work-home interaction for this population. Gender
      equivalence is also discussed.

PMID- 30099928
TI  - The neurocognitive correlates of academic diligence in adolescent girls.
AB  - Academic diligence is the ability to regulate behavior in the service of goals,
      and a predictor of educational attainment. Here we combined behavioral,
      structural MRI, functional MRI and connectivity data to investigate the
      neurocognitive correlates of diligence. We assessed whether individual
      differences in diligence are related to the interplay between frontal control and
      striatal reward systems, as predicted by the dual-systems hypothesis of
      adolescent development. We obtained behavioral measures of diligence from 40
      adolescent girls (aged 14-15 years) using the Academic Diligence Task. We
      collected structural imaging data for each participant, as well as functional
      imaging data during an emotional go-no-go self-control task. As predicted by the
      dual-systems hypothesis, we found that inferior frontal activation and
      gyrification correlated with academic diligence. However, neither striatal
      activation nor structure, nor fronto-striatal connectivity, showed clear
      associations with diligence. Instead, we found prominent activation of temporal
      areas during the go-no-go task. This suggests that academic diligence is
      associated with an extended network of brain regions.

PMID- 30099930
TI  - Coeliac disease.
AB  - : Coeliac disease (CD) develops in genetically susceptible individuals who, in
      response to unclear environmental triggers, develop an immune response triggered
      by gluten ingestion. It is now recognised as a global disease affecting about
      0.7% of the world's population. The clinical presentation ranges from
      malabsorption to asymptomatic individuals diagnosed by screening high-risk
      groups. Diagnosis requires the demonstration of small intestinal villous atrophy
      in the presence of circulating coeliac auto-antibodies and/or an unequivocal
      response to a gluten-free diet (GFD). Recent guidelines suggest that, in a subset
      of children, duodenal biopsies can be avoided in the presence of strict
      symptomatic and serological criteria. While the majority of patients respond to a
      GFD, up to 20% of patients with CD have persistent or recurrent symptoms. There
      are several aetiologies for residual or new symptoms in a patient with CD on a
      GFD, with inadvertent exposure to gluten being the most common. Following a GFD
      can be challenging for patients with CD and understanding the barriers/challenges
      faced by patients in maintaining a GFD is crucial for compliance. ABBREVIATIONS:
      AGA: anti-gliadin antibodies; Anti-DGP-ab: anti-deamidated gliadin peptide
      antibodies; Anti-tTG-ab: anti-tissue transglutaminase antibodies; ATD: auto
      immune thyroid disorders; BMD: bone mineral density; CD: coeliac disease; DH:
      dermatitis herpetiformis; EMA: anti-endomysial antibodies; FDR: first-degree
      relatives; GFD: gluten-free diet; HbA1c: haemoglobin A1c; HLA: human leucocyte
      antigen; IBS: irritable bowel syndrome; LMIC: low- and middle-income countries;
      NPV: negative predictive value; NRCD: non-responsive coeliac disease; POCT: point
      of-care tests; SDR: second-degree relatives; SIBO: small intestinal bacterial
      overgrowth; T1DM: type 1 diabetes mellitus; ULN: upper limit of normal.

PMID- 30099931
TI  - Ways of coping with excessive academic stress among Korean adolescents during
      leisure time.
AB  - PURPOSE: Korean adolescents are under excessive academic pressure because of the
      competitive college entrance examination. This study examined the characteristics
      of coping strategies on the academic stress experienced by senior high school
      students in Korea. METHODS: A total of 11 adolescents who were preparing for the
      college entrance examination participated in this study. This study employed semi
      structured in-depth interviews. A constructive grounded theory was employed to
      capture the characteristics of stress-coping strategies among adolescents.
      RESULTS: After analyzing the data, we identified four themes as strategic
      attributes of stress-coping for academic stress among Korean adolescents: (a)
      creating coping strategies in a physically active manner; (b) creating coping
      strategies in a non-physical and positive form; (c) utilizing maladaptive coping
      mechanisms; and (d) relying upon religious belief and spiritual power.
      CONCLUSION: This study indicates that Korean adolescents developed their own
      coping strategies to deal with various academic stressors through either positive
      or negative forms of leisure.

PMID- 30099929
TI  - Photodynamic Therapy for Metastatic Melanoma Treatment: A Review.
AB  - This review article is based on specifically targeted nanoparticles that have
      been used in the treatment of melanoma. According to the Skin Cancer Foundation,
      within 2017 an estimated 9730 people will die due to invasive melanoma.
      Conventional treatments for nonmalignant melanoma include surgery, chemotherapy,
      and radiation. For the treatment of metastatic melanoma, 3 therapeutic agents
      have been approved by the Food and Drug Administration: dacarbazine, recombinant
      interferon alpha-2b, and high-dose interleukin 2. Photodynamic therapy is an
      alternative therapy that activates a photosensitizer at a specific wavelength
      forming reactive oxygen species which in turn induces cell death; it is
      noninvasive with far less side effects when compared to conventional treatments.
      Nanoparticles are generally conjugated to photosynthetic drugs, since they are
      biocompatible, stabile, and durable, as well as have a high loading capacity,
      which improve either passive or active photosensitizer drug delivery to targeted
      cells. Therefore, various photosynthetic drugs and nanoparticle drug delivery
      systems specifically targeted for melanoma were analyzed in this review article
      in relation to either their passive or their active cellular uptake mechanisms in
      order to deduce the efficacy of photodynamic therapy treatment for metastatic
      melanoma which currently remains ongoing. The overall findings from this review
      concluded that no current photodynamic therapy studies have been performed in
      relation to active nanoparticle platform photosensitizer drug carrier systems for
      the treatment of metastatic melanoma, and so this type of research requires
      further investigation into developing a more efficient active nano
      photosensitizer carrier smart drug that can be conjugated to specific cell
      surface receptors and combinative monoclonal antibodies so that a further
      enhanced and more efficient form of targeted photodynamic therapy for the
      treatment of metastatic melanoma can be established.

PMID- 30099932
TI  - In silico studies and the design of novel agents for the treatment of systemic
      tuberculosis.
AB  - Tuberculosis is an ancient infectious disease, which re-emerged with the
      appearance of multidrug-resistant strains and Acquired Immune Deficiency
      Syndrome. Enoyl-acyl-carrier protein reductase (InhA) has emerged as a promising
      target for the development of antituberculosis therapeutics. The present study
      aims to develop quantitative structure-activity relationship (QSAR) models for a
      series of arylcarboxamides as InhA inhibitors. The QSAR models were calculated on
      the basis of optimal molecular descriptors based on the simplified molecular
      input line-entry system (SMILES) notation with the Monte Carlo method as a model
      developer. The molecular docking study was used for the final assessment of the
      developed QSAR model and designed novel inhibitors. Methods used for the
      validation indicated that the predictability of the developed model was good.
      Structural indicators defined as molecular fragments responsible for increases
      and decreases of the studied activity were defined. The computer-aided design of
      new compounds as potential InhA inhibitors was presented. The Monte Carlo
      optimisation was capable of being an efficient in silico tool for developing a
      model of good statistical quality. The predictive potential of the applied
      approach was tested, and the robustness of the model was proven using different
      methods. The results obtained from molecular docking studies were in excellent
      correlation with the results from QSAR studies. The presented study can be useful
      in the search for novel anti-tuberculosis therapeutics based on InhA inhibition.

PMID- 30099933
TI  - A randomised controlled trial exploring the effects of different beverages
      consumed alongside a nitrate-rich meal on systemic blood pressure.
AB  - BACKGROUND:: Ingestion of nitrate (NO3-)-containing vegetables, alcohol and
      polyphenols, separately, can reduce blood pressure (BP). However, the
      pharmacokinetic response to the combined ingestion of NO3- and polyphenol-rich or
      low polyphenol alcoholic beverages is unknown. AIM:: The aim of this study was to
      investigate how the consumption of low and high polyphenolic alcoholic beverages
      combined with a NO3--rich meal can influence NO3- metabolism and systemic BP.
      METHODS:: In a randomised, crossover trial, 12 normotensive males (age 25 +/- 5
      years) ingested an acute dose of NO3- (~6.05 mmol) in the form of a green leafy
      salad, in combination with either a polyphenol-rich red wine (NIT-RW), a low
      polyphenol alcoholic beverage (vodka; NIT-A) or water (NIT-CON). Participants
      also consumed a low NO3- salad and water as a control (CON; ~0.69 mmol NO3-). BP
      and plasma, salivary and urinary [NO3-] and nitrite ([NO2-]) were determined
      before and up to 5 h post ingestion. RESULTS:: Each NO3--rich condition elevated
      nitric oxide (NO) biomarkers when compared with CON ( P < 0.05). The peak rise in
      plasma [NO2-] occurred 1 h after NIT-RW (292 +/- 210 nM) and 2 h after NIT-A (318
      +/- 186 nM) and NIT-CON (367 +/- 179 nM). Systolic BP was reduced 2 h post
      consumption of NIT-RW (-4 mmHg), NIT-A (-3 mmHg) and NIT-CON (-2 mmHg) compared
      with CON ( P < 0.05). Diastolic BP and mean arterial pressure were also lower in
      NIT-RW and NIT-A compared with NIT-CON ( P < 0.05). CONCLUSIONS:: A NO3--rich
      meal, consumed with or without an alcoholic beverage, increases plasma [NO2-] and
      lowers systemic BP for 2-3 h post ingestion.

PMID- 30099934
TI  - Pharmacist Perception of a Mobile Application Audience Response System for Remote
      Pharmacy Continuing Education Participants.
AB  - INTRODUCTION: Interactive audience response during continuing education (CE) in
      pharmacy practice increases audience involvement. However, remote-site
      participants may not have access to interactive technology. This study explores
      the perceptions of a mobile application audience response system (ARS) by remote
      pharmacy CE participants. Secondarily, we evaluatedinterest in continued use of
      ARS, as well as willingness to use as an assessment tool for CE effectiveness.
      METHODS: Pharmacists participating in CE sessions remotely within a health system
      were provided a unique ARS session code to enter into a free mobile application.
      Participants then responded to ARS presentation questions. An online survey link
      was e-mailed to all potential remote participants inquiring about perceptions of
      ARS use. RESULTS: Of the 52 potential remote users, 28 (53.8%) responded to the
      survey. The top 3 positive responses included the availability of free software
      (71.4%), anonymity (57.1%), and ease of use (53.6%). Top 2 barriers included
      slowing the process down (14.3%) and requiring the use of application software
      (14.3%). DISCUSSION: Interactive software during pharmacy CE lectures for
      participants at remote locations within a health system was well accepted. ARS
      should be considered and further studied for CE lectures at institutions with
      remote participants.

PMID- 30099935
TI  - Decision-makers and mediators in a home healthcare digitisation process: nurses'
      experiences of implementation and use of a decision support system.
AB  - BACKGROUND: This study focuses on a decision support system (DSS) for home
      healthcare and the implementation of it. AIM: To describe home healthcare nurses'
      experiences of the implementation and use of a new DSS, with a focus on how it
      influences decision making in everyday work practice. DESIGN: A qualitative
      research design. METHODS: Data was collected through three focus group interviews
      with six home healthcare nurses.The data analysis was drawn from Burnard's method
      for content analysis. RESULTS: The DSS was experienced as bringing support to
      decisions, but sometimes incompatible with home healthcare nurses' work practice.
      Professional understanding and the DSS were sometimes experienced as parallel
      support systems not assisting work across healthcare organisations. CONCLUSION:
      When a DSS is used to transform work of healthcare organisations several aspects
      should be highlighted. If the organisation does not consider these aspects,
      nurses may adopt a role as mediator in the implementation process.

PMID- 30099936
TI  - Risk Stratification With Coccidioidal Skin Test to Prevent Valley Fever Among
      Inmates, California, 2015.
AB  - Two California state prisons (A and B) have very high rates of coccidioidomycosis
      (Valley Fever). The prison health care service sought to improve their prevention
      strategy by risk stratification with a newly available spherulin-based
      Coccidioides delayed-type hypersensitivity test. Of the 36,789 voluntarily
      screened inmates, 4.7% experienced adverse reactions. A positive test (8.6% of
      those tested) was independently associated with (1) incarceration at prisons A
      and B, (2) admission to prison from a Coccidioides-endemic county, (3) length of
      stay at prisons A and B, and (4) increasing age. These findings suggest that the
      test is safe and performing well at risk stratification; the prison system now
      restricts inmates with negative tests from prisons A and B. This novel use of the
      test might benefit other coccidioidomycosis prevention programs.

PMID- 30099938
TI  - A new biofeedback approach for the control of masseter and temporal myalgia:
      Utilization of an awake posterior interocclusal device.
AB  - OBJECTIVE: To evaluate the improvement in reducing the pain of patients diagnosed
      with masticatory myofascial pain and bruxism when undergoing treatment with a
      partial posterior interocclusal device for the management and control of awake
      bruxism through biofeedback. METHODS: Sixty patients were evaluated during the
      following periods: pretreatment, 7, 30, and 90 days. The evaluation was carried
      out by measuring the reduction in pain using clinical and numerical scales.
      RESULTS: The majority of the patients who complained of masticatory myofascial
      pain, TMJ, and neck pain experienced a significant reduction in pain between t0
      and t30 (p < 0.0001). After 30 days of using the device, the improvement remained
      at the same level, without any recurrence of pain up to t90. CONCLUSION: The
      utilization of a posterior interocclusal device for the management and control of
      awake bruxism through biofeedback contributed to the reduction of pain in the
      majority of patients.

PMID- 30099937
TI  - Experiences of advanced dementia care in seven European countries: implications
      for educating the workforce.
AB  - BACKGROUND: There is a paucity of robust research concerning the care experiences
      of peoplewith advanced dementia within Europe. It is essential to understand
      these experiences if weare to address care inequalities and create impactful
      dementia policies to improve servicesthat support individuals and enable family
      caring. OBJECTIVES: To identify the strengths and weaknesses in daily life
      perceived by people with dementia and family caring across Europe by exemplifying
      experiences and the range of typical care settings for advanced dementia care in
      seven partner countries. METHODS: Twenty two in-depth qualitative case studies
      were completed in seven European countries across a range of care settings
      considered typical within that country. Narrative accounts of care illuminated a
      unique set of experiences and highlighted what was working well (strengths or
      positive aspects) and not so well (weaknesses or negative aspects) for people
      with advanced dementia and family caring. A constant comparative method of
      analysis through thematic synthesis was used to identify the common themes.
      RESULTS: Eight key themes were identified; Early diagnosis, good coordination
      between service providers, future planning, support and education for carers,
      enabling the person with dementia to live thebest life possible and education on
      advanced dementia for professional and family caregiverswere all significant and
      recurring issues considered important for care experiences to bepositive.
      CONCLUSION: People with advanced dementia may have limited opportunities for self
      realization and become increasingly reliant on the support of others to maximize
      their health and well-being. Careful attention must be given to their
      psychosocial well-being, living environment and family caring to enable them to
      live the best life possible. Building on what the case studies tell us about what
      works well, we discuss the potential for integrating the findings into
      interprofesional learning solutions for the professional workforce across Europe
      to champion practice-based change.

PMID- 30099939
TI  - Current Approaches to Ischemic Mitral Regurgitation: Repair, Replacement, or
      Nothing.
AB  - The treatment strategy for ischemic mitral regurgitation (MR) continues to evolve
      with the completion of multicenter trials and the advancement of surgical and
      percutaneous interventional techniques. This review defines ischemic MR, outlines
      key clinical trials that assess surgical and interventional approaches, and
      reports the main elements of recent national guidelines for decision making in
      treatment of ischemic MR. New findings in percutaneous mitral valve repair and
      replacement for ischemic MR will also be described. Effective perioperative care
      of patients with ischemic MR requires clinicians to be well versed in the most up
      to-date recommendations and emerging technological developments.

PMID- 30099940
TI  - Prevalence of low-calorie sweetener intake in South Asian adults.
AB  - BACKGROUND: Consumption of low-calorie sweeteners (LCS) has increased in the US
      and is associated with cardiometabolic risk. No data exist on LCS consumption in
      South Asians. AIM: The aim of this study was to assess the prevalence of LCS use
      across socio-demographic characteristics, chronic disease status, and
      cardiometabolic risk factors. METHODS: Cross-sectional analyses were conducted
      using data from the Mediators of Atherosclerosis in South Asians Living in
      America study ( N = 892; 47% women; mean age = 55 (standard deviation = 9.4) y).
      Chi-squared and ANOVA tests were used to compare LCS consumption across socio
      demographic characteristics and cardiometabolic risk factors. RESULTS: Twenty-two
      percent of participants reported LCS use, with higher consumption among men and
      those with longer residency in the US. LCS use was associated with adiposity and
      higher odds of hypertension, high cholesterol, and diabetes. CONCLUSIONS: LCS use
      is prevalent among South Asians, emphasizing the need for long-term, prospective
      studies to investigate its role in incident cardiometabolic risk in an already
      metabolically vulnerable population.

PMID- 30099941
TI  - Incidence of cardiovascular risk factors in female patients with systemic lupus
      erythematosus: a 3-year follow-up cohort.
AB  - Objectives To evaluate the incidence and variability of traditional coronary
      artery disease (CAD) risk factors in a cohort of lupus patients and to
      investigate if prednisone use predicts an increase in the number of risk factors.
      Methods A total of 151 women, 37.8 +/- 11.1 (mean +/- SD) years old at baseline,
      were reevaluated after a median period of 39 (interquartile range 36.5-42.0)
      months. The cumulative incidence of traditional risk factors, the incidence rate
      (with 95% confidence interval) of hypertension, diabetes, dyslipidemia and
      hypertriglyceridemia, and the frequency of the risk factors' disappearance were
      calculated. Metabolic syndrome (MetS) and Framingham risk score (FRS) were
      computed. Logistic regression was used to investigate if maximum or cumulative
      prednisone dose used during follow-up predicted an increase in the
      cardiometabolic risk factors' number. Results The cumulative incidence of risk
      factors varied from 39.1% (abdominal obesity) to zero (smoking), and the
      incidence rate varied from 133.2 (87.8-178.6) per 1000 person-years
      (dyslipidemia) to 10.4 (1.3-19.5) per 1000 person-years (diabetes). The
      cumulative incidence for MetS was 18.8%, and 11.7% of 143 patients with low FRS
      at baseline (T1) were classified in the high-risk category at the end of the
      study (T2). Dyslipidemia was the most variable risk factor, with 43.5%
      disappearance at T2. The maximum prednisone dose used during follow-up was
      borderline ( p = 0.050) for prediction of an increase in the number of
      cardiometabolic risk factors in an adjusted model for antimalarial use, modified
      Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and age.
      Conclusion The authors described high incidence and variability of CAD risk
      factors in female lupus patients, with higher prednisone dose being borderline
      for an increase in the number of cardiometabolic risk factors.

PMID- 30099942
TI  - Stem cells for lupus nephritis: a concise review of current knowledge.
AB  - Lupus nephritis (LN), a common manifestation of systemic lupus erythematosus
      (SLE), accounts for significant morbidity and mortality in SLE patients. Since
      the available standard therapies and biologic agents for LN are yet to achieve
      the desired response and have considerable secondary effects, stem cell therapy
      has now emerged as a new approach. This therapy involves the transplantation of
      hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Our current
      review will highlight the progress of stem cell therapy for LN, along with the
      challenges encountered and the future direction of this approach.

PMID- 30099943
TI  - Linear gingival erythema in a child with systemic lupus erythematosus: an
      association or a coincidence?

PMID- 30099944
TI  - The Substance Abuse and Mental Health Services Administration (SAMHSA): New
      Directions.

PMID- 30099945
TI  - Frequent relapses in a child with nephrotic syndrome due to PLEVA.
AB  - A seven-year-old boy with nephrotic syndrome presented with a frequent rash along
      with relapse of nephrotic syndrome. Clinical and histological features were
      suggestive of pityriasis lichenoides et varioliformis acuta (PLEVA). Treatment of
      the condition with doxycycline led to the cure of the lesions as well as the
      relapses.

PMID- 30099946
TI  - Do Support and Strain With Adult Children Affect Mothers' and Fathers' Physical
      Activity?
AB  - Physical activity is central to health. Parents tend to have lower levels of
      physical activity than the childless, however, little is known about how adult
      child-parent relationship quality matters for mothers' and fathers' physical
      activity trajectories. Nationally representative panel data from the Americans'
      Changing Lives survey (1986-2012) are used to analyze multilevel-ordered logistic
      regression models. Greater social support from adult children is associated with
      more frequent active exercise, and higher strain with adult children is related
      to more frequent active exercise and walking. A significant gender interaction
      suggests that strain with adult children is related to greater exercise among men
      more so than women, but this interaction is attenuated after adjusting for
      cigarette smoking, another gendered way of coping with stress. This study
      contributes to a more nuanced understanding of how different dimensions of
      intergenerational relationships shape health behaviors across the life course.

PMID- 30099947
TI  - Hyperinflation: Definitions and Causes.
AB  - Hundreds of oral and injectable generic drugs have seen dramatic price increases
      during the 2010s. Several reasons for the astronomic price increases have been
      postulated, ranging from reduced competition, shortages in the manufacturing
      supply chain, very small markets, market consolidation, the Unapproved Drugs
      Initiative of 2006, and unanticipated manufacturing safety issues. In one survey,
      over 90% of hospital administrators reported that higher drug prices had a
      moderate or severe impact on their budgets. Whereas compounding pharmacies may
      present an effective solution to high drug prices, it is a potentially dangerous
      one, as the case of New England Compounding Center makes clear. The risks make a
      meticulous vetting process necessary.

PMID- 30099948
TI  - Real-Time 3D Virtual Target Fluoroscopic Display for Challenging Hepatocellular
      Carcinoma Ablations Using Cone Beam CT.
AB  - Three-dimensional virtual target fluoroscopic display is a new guidance tool that
      can facilitate challenging percutaneous ablation. The purpose of this study was
      to assess the feasibility, local efficacy, and safety of liver ablation assisted
      by three-dimensional virtual target fluoroscopic display. Sixty-seven
      hepatocellular carcinomas (mean diameter: 31 mm, range: 9-90 mm, 24 >= 30 mm, 16
      of an infiltrative form) in 53 consecutive patients were ablated using
      irreversible electroporation (n = 39), multibipolar radiofrequency (n = 25), or
      microwave (n = 3) under a combination of ultrasound and three-dimensional virtual
      target fluoroscopic display guidance because the procedures were considered to be
      unfeasible under ultrasound alone. This guidance technology consisted of real
      time fluoroscopic three-dimensional visualization of the tumor previously
      segmented from cone beam computed tomography images acquired at the start of the
      procedure. The results were assessed by cross-sectional imaging performed at 1
      month and then every 3 months in the event of complete ablation. Factors
      associated with overall local tumor progression (initial treatment failure and
      subsequent local tumor progression) were assessed using a logistic regression
      model. Sixty-one (91%) tumors were completely ablated after 1 (n = 53) or 2 (n =
      8) procedures. After a median follow-up of 12.75 months (1-23.2) of the 61 tumors
      displaying imaging characteristics consistent with complete ablation at 1 month,
      local tumor progression was observed in 9, so the overall local tumor progression
      rate was 22.3% (15 of 67). Under multivariate analysis, dome locations and
      infiltrative forms were associated with local tumor progression. No major
      complications occurred. Three-dimensional virtual target fluoroscopic display is
      a feasible and efficient image guidance tool to facilitate challenging ablations
      that are generally considered as infeasible using ultrasound alone.

PMID- 30099951
TI  - Significant Publications on Infectious Diseases Pharmacotherapy in 2017.
AB  - PURPOSE: The most significant peer-reviewed articles pertaining to infectious
      diseases (ID) pharmacotherapy, as selected by panels of ID pharmacists, are
      summarized. SUMMARY: Members of the Houston Infectious Diseases Network (HIDN)
      were asked to nominate peer-reviewed articles that they believed most contributed
      to the practice of ID pharmacotherapy in 2017, including the areas of human
      immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). A
      list of 33 articles related to general ID pharmacotherapy and 4 articles related
      to HIV/AIDS was compiled. A survey was distributed to members of the Society of
      Infectious Diseases Pharmacists (SIDP) for the purpose of selecting 10 articles
      believed to have made the most significant impact on general ID pharmacotherapy
      and the single significant publication related to HIV/AIDS. Of 524 SIDP members
      who responded, 221 (42%) and 95 (18%) members voted for general pharmacotherapy-
      and HIV/AIDS-related articles, respectively. The highest ranked articles are
      summarized below. CONCLUSION: Remaining informed on the most significant ID
      related publications is a challenge when considering the large number of ID
      related articles published annually. This review of significant publications in
      2017 may aid in that effort.

PMID- 30099953
TI  - Cyclic changes in sensations to painful stimuli in migraine patients.
AB  - Introduction Migraine is characterized by cycling phases (interictal, preictal,
      ictal and postictal) with differing symptoms, while in chronic tension type
      headache pain phases are fluctuating. The question we asked is whether these
      phases are associated with changes in parameters of somatosensation and axon
      reflex erythema. Methods Patients with episodic migraine and chronic tension type
      headache were examined psychophysically in the interictal, preictal and ictal
      phase and healthy subjects on five different test days. Thresholds and
      suprathreshold ratings of pressure and electrical pain were assessed on three
      different regions of the head. In migraine patients and in healthy controls,
      electrically induced axon-reflex erythema was measured in the area of the first
      trigeminal branch. All migraine patients filled out questionnaires about
      prodromal symptoms at every visit. Results The axon-reflex erythema was always
      larger in patients with migraine in contrast to healthy subjects. The pressure
      pain threshold was lower in migraine patients and chronic tension type headache
      in comparison to healthy subjects. Electrical pain thresholds did not differ
      between headache patients and healthy subjects and showed no changes between the
      phases. However, suprathreshold pain ratings showed less habituation solely in
      the preictal phase of migraine. The number of prodromal symptoms in migraine
      patients was increased in the preictal and ictal phase. Discussion Reduced
      habituation was the unique sign of the preictal phase in migraine patients,
      independently of prodromal symptoms, whereas a larger axon-reflex erythema and
      higher pressure pain sensitivity are constitutional and non-phase dependent
      properties of migraine. Reduced inhibitory mechanisms in the preictal phase may
      contribute to trigger headache attacks in migraine.

PMID- 30099952
TI  - Sonography of the optic nerve sheath diameter before and after microsurgical
      closure of a dural CSF fistula in patients with spontaneous intracranial
      hypotension - a consecutive cohort study.
AB  - Objective Spontaneous intracranial hypotension is caused by spinal cerebrospinal
      fluid leakage. Patients with orthostatic headaches and cerebrospinal fluid
      leakage show a decrease in optic nerve sheath diameter upon movement from supine
      to upright position. We hypothesized that the decrease in optic nerve sheath
      diameter upon gravitational challenge would cease after closure of the leak.
      Methods We included 29 patients with spontaneous intracranial hypotension and
      refractory symptoms admitted from 2013 to 2016. The systematic workup included:
      Optic nerve sheath diameter sonography, spinal MRI and dynamic myelography with
      subsequent CT. Microsurgical sealing of the cerebrospinal fluid leak was the aim
      in all cases. Results Of 29 patients with a proven cerebrospinal fluid leak, one
      declined surgery. A single patient was lost to follow-up. In 27 cases, the
      cerebrospinal fluid leak was successfully sealed by microsurgery. The width of
      the optic nerve sheath diameter in supine position increased from 5.08 +/- 0.66
      mm before to 5.36 +/- 0.53 mm after surgery ( p = 0.03). Comparing the response
      of the optic nerve sheath diameter to gravitational challenge, there was a
      significant change from before (-0.36 +/- 0.32 mm) to after surgery (0.00 +/-
      0.19 mm, p < 0.01). In parallel, spontaneous intracranial hypotension-related
      symptoms resolved in 26, decreased in one and persisted in a single patient
      despite recovery of gait. Conclusions The sonographic assessment of the optic
      nerve sheath diameter with gravitational challenge can distinguish open from
      closed spinal cerebrospinal fluid fistulas in spontaneous intracranial
      hypotension patients. A response to the gravitational challenge, that is, no more
      collapse of the optic nerve sheath while standing up, can be seen after
      successful treatment and correlates with the resolution of clinical symptoms.
      Sonography of the optic nerve sheath diameter may be utilized for non-invasive
      follow-up in spontaneous intracranial hypotension.

PMID- 30099954
TI  - A case report of isolated orbital vasculitis mimicking retinal migraine: A
      potential cause of recurrent transient monocular blindness and ipsilateral
      headache.
AB  - Background Retinal migraine is an important differential diagnosis of recurrent
      transient monocular blindness accompanied by headache when other etiologies are
      excluded. Here, we report a case of orbital vasculitis which initially mimicked
      retinal migraine. Case report A 47-year-old woman had recurrent episodes of fully
      reversible transient monocular blindness accompanied by ipsilateral headache for
      15 months. The patient's neuroimaging and cardiac and ophthalmologic evaluations
      were normal. With a diagnosis of retinal migraine, her symptoms remitted in
      response to prophylactic treatment with topiramate and propranolol for 8 months.
      Three months after discontinuation of medications, transient monocular blindness
      recurred. High-resolution vessel wall magnetic resonance imaging revealed
      enhancement of the ipsilateral orbital vessels. Isolated orbital vasculitis was
      diagnosed. Complete remission of transient monocular blindness was achieved after
      steroid pulse therapy. Discussion Isolated orbital vasculitis should be
      considered in differential diagnosis of recurrent transient monocular blindness
      and ipsilateral headache. High-resolution vessel wall magnetic resonance imaging
      can be helpful for the diagnosis.

PMID- 30099955
TI  - Reliable self-application of short stretch leg compression: Pressure measurements
      under self-applied, adjustable compression wraps.
AB  - Aim Self-application of properly performed compression bandages is generally
      considered as problematic. Therefore, the aim of this study was to measure the
      pressure of self-applied short stretch adjustable compression wrap compression
      systems (Juxta fitTM) and to compare the results with the pressure achieved by
      bandaging other legs using the same material. Methods In the two training courses
      for nurses, specifically interested in leg ulcer treatment, the new bandage type
      of adjustable compression wrap was explained and workshops were organized, in
      which the interface pressure achieved by Juxta fitTM was measured. In the first
      course, the nurses applied the compression system to each other, and in the
      second course, another group did it on their own legs. Bandagers were instructed
      to apply the system strongly, with a target range of more than 50-60 mmHg.
      Results In the first course with mutual application ( n = 34), the median
      pressure at the medial lower leg was 58.5 mmHg (minimal 31, maximal value 137
      mmHg), in the second course in which self-application was tested ( n = 36), the
      corresponding values were 61.5 mmHg (minimum 35, maximum 102 mmHg). No pressures
      less than 30 mmHg were seen on the distal calf in either group. Conclusions In
      contrast to short stretch bandages that are frequently applied by bandagers with
      too low pressure, the adjustable compression wrap devices handled by the patients
      themselves produce more appropriate and more consistent pressure.

PMID- 30099956
TI  - Facial Growth of Patients With Complete Unilateral Cleft Lip and Palate Treated
      With Alveolar Bone Grafting at 6 Years.
AB  - OBJECTIVE: To investigate the effect that alveolar bone grafting (ABG) around 6
      years of age has on facial growth by assessing craniofacial growth outcomes.
      DESIGN: Retrospective cohort study. SETTING: North American cleft centers.
      PARTICIPANTS: A total of 33 children with complete unilateral cleft lip and
      palate who were consecutively treated with secondary ABG around 6 years of age
      were compared to 148 participants from 4 centers with late secondary ABG.
      METHODS: Preorthodontic standardized lateral cephalometric radiographs were
      analyzed and traced according to the Americleft Study protocol. Sixteen angular
      and 2 proportional measurements were performed. The outcomes of all ABG were
      assessed using the Standardized Way to Assess Graft scale. Measurement means from
      the study center (SC) were compared to 4 North American centers using analysis of
      variance and Welch modified t tests, and P < .05 was considered statistically
      significant. RESULTS: For the SC, the mean age (SD) at the time of bone graft was
      5.85 (0.71) years and the mean age at the time of the lateral cephalogram was
      13.4 (1.8) years. The sagittal maxillary prominence of the SC was comparable to
      the 4 other centers. The mean SNA (78.1 [4.3]) for the SC was significantly
      higher compared to one center that used primary bone grafting ( P = .03). The
      soft tissue mean ANB (3.52 [4.09]) for the SC was significantly lower compared to
      3 of the centers. CONCLUSIONS: Early secondary ABG around 6 years of age did not
      result in reduced midface projection as assessed by SNA and thus did not
      compromise anterior maxillary growth.

PMID- 30099957
TI  - Pulmonary arterial hypertension induced by a novel method: Twice-intraperitoneal
      injection of monocrotaline.
AB  - Pulmonary arterial hypertension (PAH) in humans manifests as a chronic process.
      However, PAH induced by high-dose monocrotaline (MCT) in animals occurs as a
      subacute process. To establish a chronic PAH model, rats were randomly divided
      into three groups, control (ctrl), single injection (SI), and twice injection
      (TI) groups. Rats in the SI group received a single intraperitoneal injection of
      40 mg/kg MCT on day 0. Rats in the TI group received twice injections of 20 mg/kg
      MCT on days 0 and 7. Survival percentage, characteristic changes of pulmonary
      arterial variables, and right ventricular features were evaluated. Thirty-five
      days after the first MCT injection, survival percentage in TI group was higher
      than that in the SI group. The mean pulmonary arterial pressure (mPAP), right
      ventricular hypertrophy index (RVHI), pulmonary vascular remodeling, serum tumor
      necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6) were higher either in
      SI or in TI 28 and 35 days after the first MCT injection. The rats in the SI and
      TI groups exhibited higher right ventricle end diastolic diameter (RVEDD) and
      lower adjusted pulmonary artery acceleration time (PAAT/HR), tricuspid annular
      plane systolic excursion (TAPSE), cardiac output (CO) and right ventricle
      fractional shortening (RVFS) when compared with controls. However, mPAP, RVHI,
      TAPSE, PAAT/HR, CO, TNFalpha, and IL-6 were lower and RVEDD were higher in the TI
      group than in the SI group. Pulmonary macrophage infiltration and right ventricle
      (RV) fibrosis were lower in TI than SI groups. The cardiomyocyte cross-sectional
      area and the beta myosin heavy chain (MYH7) mRNA level of RV were lower in TI
      than SI, whereas alpha myosin heavy chain (MYH6) was increased. These results
      show that two intraperitoneal injections of 20 mg/kg MCT with seven days interval
      could induce a model similar to chronic PAH with increased survival percentage in
      rats. Impact statement We demonstrated previously that a single intraperitoneal
      injection of 40 mg/kg MCT produced a subacute, not chronic, PAH model in rats,
      and the short survival periods of these rats did not represent adequately the
      chronic PAH seen in humans. To overcome this limitation, in this study, the
      single dose of 40 mg/kg MCT was divided into twice injections of 20 mg/kg with an
      interval of seven days. This modified administration of MCT produced an animal
      model much more similar to chronic PAH with prolonged survival and characteristic
      changes of structures and function in pulmonary arteries and right ventricles.

PMID- 30099958
TI  - Detection and interpretation of fecal host mRNA in rural Malawian infants aged 6
      12 months at risk for environmental enteric dysfunction.
AB  - Recent studies have suggested that environmental enteric dysfunction can be
      assessed in rural African children by measuring levels of fecal mRNA transcripts.
      The field collection of fecal samples is less invasive and cumbersome than
      administration of the lactulose:mannitol test, which is typically used to assess
      environmental enteric dysfunction. This study sought to determine if, as in
      children aged 12-60 months, an array of seven fecal host transcripts (CD53, CDX1,
      HLA-DRA, TNF, S100A8, MUC12, and REG1A) could predict environmental enteric
      dysfunction in rural African infants. Host fecal transcript abundance was
      correlated to the percentage of lactulose (%L) excreted in the urine for 340
      samples from Malawian children aged 6-12 months. Permeability was categorized as
      not severe (%L < 0.45) and severe (%L >= 0.45). This study found the prevalence
      of severe environmental enteric dysfunction to be 114/834 (14%), lower than what
      was previously reported for 12-60 months old children, 595/1521 (39%, P = 0.001).
      In linear regression analysis with the seven host transcripts, two were
      associated with %L: beta coefficients of -1.843 ( P = 0.035) and 0.215 ( P =
      0.006) for CDX1 and REG1A, respectively. The seven fecal host transcripts in a
      random forest model did not predict severe environmental enteric dysfunction.
      Future models utilizing different transcripts identified from an untargeted,
      agnostic assessment of all potential host transcripts could provide accurate
      predictions of environmental enteric dysfunction in infants. Impact statement
      Environmental enteric dysfunction (EED) is associated with reduced linear growth.
      The dual sugar absorption test has been used as a non-invasive method to
      determine the gut health of individuals. Alternative methods using fecal host
      mRNAs as predictors of the gut health are promising. In older children, we have
      determined that seven transcripts can predict the gut health in a random forest
      model. Our current study determined that the host fecal mRNA is abundant in
      infants and toddlers alike. Severe EED in rural Malawian children is less
      prevalent in infants than in young children. REG1A and CDX1 are associated with
      gut health. Fecal host mRNA may well be a means to assess gut health in African
      infants, but the panel of transcripts used to do this will differ from that in
      older children.

PMID- 30099960
TI  - Regulation of birthweight by placenta-derived miRNAs: evidence from an arsenic
      exposed birth cohort in Bangladesh.
AB  - Altered expression of microRNAs (miRNAs) is implicated in fetal growth. However,
      the mechanisms by which placenta-derived miRNAs regulate birthweight are not well
      understood. In Phase 1, we compared the expression of 754 miRNAs in the placenta
      of mothers from two extreme birthweight groups (0.8-2.2 kg vs. 3.3-3.9 kg, n = 77
      each) selected from an arsenic-exposed Bangladeshi birth cohort (n = 1,141). We
      identified 49 miRNAs associated with the extreme birthweight groups and/or
      gestational age in Phase 1, which were further analyzed in Phase 2 among 364
      randomly selected mother-infant pairs. Gestational age was determined by
      ultrasound. Causal mediation analysis was used to estimate the effect of miRNAs
      on birthweight considering gestational age a mediator, adjusting for core blood
      arsenic and other risk factors. miR-1290, miR-195, and let-7g showed significant
      inverse associations with gestational age, while miR-328 showed significant
      positive association [false discovery rate (FDR) <0.05]. Via changing gestational
      age, miR-1290, miR-195, and miR-27a showed significant inverse associations with
      birthweight, while miR-328 and miR-324-5p showed significant positive
      associations (FDR <0.05). The effect of miRNAs on birthweight varied by
      gestational age (for miR-1290, miR-195, miR-328) and in utero arsenic exposure
      (for miR-1290): stronger effect was observed among infants delivered early in
      gestation or exposed to higher concentrations of arsenic in cord blood. Gene
      enrichment analysis with in silico predicted targets identified cell
      proliferation, inflammation, apoptosis, insulin, and IGF family signaling
      cascades associated with these miRNAs. Future studies are warranted to replicate
      these findings and assess these miRNAs as early biomarkers of fetal growth.

PMID- 30099961
TI  - Characterization of Factors Affecting the Detection Limit of EGFR p.T790M in
      Circulating Tumor DNA.
AB  - OBJECTIVE: Circulating tumor DNA is a promising noninvasive tool for cancer
      monitoring. One of the challenges in applying this tool is the detection of low
      frequency mutations. The detection limit of these mutations varies between
      different molecular methods. The aim of this study is to characterize the factors
      affecting the limit of detection for epidermal growth factor receptor p.T790M
      mutation in circulating tumor DNA of patients with lung adenocarcinoma. METHODS:
      DNA was extracted from plasma samples of 102 patients. For sequencing the DNA, we
      used 2 different next-generation sequencing-based platforms: Ion Torrent Personal
      Genome Machine (56 cases) and Roche/454 (46 cases). Serially diluted synthetic
      DNA samples carrying the p.T790M mutation were sequenced using the Ion Torrent
      Personal Genome Machine for validation. Limit of detection was determined through
      the analysis of non-hot-spot nonreference reads, which were regarded as
      sequencing artifacts. RESULTS: The frequency of the non-hot-spot nonreference
      reads was higher in Ion Torrent Personal Genome Machine compared to Roche/454
      (0.07% +/- 0.08% and 0.03% +/- 0.06%, respectively, P < .001). We found that
      different base type substitutions occur with different frequency. Since the base
      substitution leading to p.T790M mutation is C>T transition, its frequency was
      used to determine the limit of detection for the assay. Based on the C>T non-hot
      spot nonreference allele frequency, we found that the limit of detection is 0.18%
      in Ion Torrent Personal Genome Machine and 0.1% in Roche/454. Based on these
      values, 48% and 56% of the cases were positive for T790M mutation in Ion Torrent
      Personal Genome Machine and Roche/454 groups, respectively. Agreement between
      duplicates was 76% in Ion Torrent Personal Genome Machine and 72% in Roche/454.
      Using serially diluted synthetic DNA samples carrying the p.T790M mutation, we
      could identify mutations with allele frequency of 0.18% or more using the Ion
      Torrent Personal Genome Machine, supporting our approach to determine the
      detection limit. CONCLUSION: Both the sequencing platform and the specific
      nucleotide change affect the limit of detection and should therefore be
      determined in the validation process of new assays.

PMID- 30099962
TI  - Prophylactic and therapeutic effects of twice-daily famciclovir administration on
      infectious upper respiratory disease in shelter-housed cats.
AB  - Objectives In humans with herpetic disease, early or pre-emptive famciclovir
      therapy reduces disease duration and severity. This prospective, masked, placebo
      controlled study tested therapeutic and prophylactic effects of two famciclovir
      doses given to cats for 7 days following shelter entry. Methods Cats were
      assigned to prophylactic or therapeutic study arms based on clinical evidence of
      herpetic disease at study entry. Cats in the therapeutic arm received no
      treatment (n = 19), placebo (lactulose; n = 18) or famciclovir at ~30 (n = 21) or
      ~90 mg/kg (n = 20) orally q12h for 7 days. Cats in the prophylactic arm received
      no treatment (n = 25) or famciclovir at ~30 (n = 28) or ~90 mg/kg (n = 27) orally
      q12h for 7 days. Disease scores, body weight, conjunctival feline herpesvirus 1
      (FHV-1) shedding, and adoption rates were recorded on days 1 (admission), 8 (end
      of therapy) and 15 (1 week after cessation of therapy). Results No significant
      differences in clinical scores were observed among groups in the prophylactic or
      therapeutic arms at any of the three time points. However, within the therapeutic
      arm, viral shedding on day 8 was significantly higher in cats receiving no
      treatment than in those receiving ~30 or ~90 mg/kg famciclovir, and this effect
      persisted 1 week after famciclovir was stopped (day 15) only in cats receiving
      ~30 mg/kg, although this approached significance in cats receiving ~90 mg/kg. No
      significant differences in adoption rates were detected among groups in either
      arm throughout the study. Conclusions and relevance Although we did not
      demonstrate a statistically or clinically significant effect of famciclovir
      administration upon clinical signs of infectious upper respiratory disease or
      adoption, when it was administered at ~30 or ~90 mg/kg q12h for 1 week
      famciclovir reduced conjunctival FHV-1 shedding. This suggests a potential role
      in interrupting the infectious cycle within a shelter population; however cost in
      time and resources, and stress and pathogen transmission induced by oral
      administration should be considered.

PMID- 30099963
TI  - Multiorgan dysfunction syndrome in feline sepsis: prevalence and prognostic
      implication.
AB  - Objectives The current study was designed to evaluate the prevalence and
      prognostic significance of multi-organ dysfunction syndrome (MODS) in cats with
      sepsis. Methods Cats hospitalised in the intensive care unit of a veterinary
      university hospital with a diagnosis of sepsis were prospectively enrolled and
      divided according to disease severity and outcome (survivors; non-survivors). The
      feline acute patient physiological and laboratory evaluation (APPLE) scores were
      calculated upon admission, as previously described. Specific criteria to identify
      selected organ dysfunction (hepatic, renal, respiratory, cardiocirculatory,
      haemostatic) were adapted from the available human and veterinary literature, and
      evaluated at baseline and at the end of hospital stay. MODS was defined as the
      presence of at least two dysfunctional organs simultaneously. Non-parametric
      statistics were used for comparisons. Univariate and multivariate regression
      analyses to evaluate significant risk factors for death were carried out.
      Correlations between variables were assessed by the Spearman's rank correlation
      coefficient. Significance was set at P <0.05. Results A total of 43 cats with
      heterogeneous sources of sepsis were included. MODS was identified in 25/43 cats
      upon admission and in 32/43 cats at the end of hospital stay. Regression analyses
      showed a significantly elevated odds ratio for mortality for the presence of
      MODS, renal and cardiovascular dysfunction upon admission, as well as for the
      number of dysfunctional organs. The latter was the only variable retained by the
      model from the multivariate binary logistic regression analysis. Significant
      correlations were documented between the number of dysfunctional organs and the
      APPLE scores. Conclusions and relevance MODS is a frequent complication of feline
      sepsis, and is associated with worse outcomes. In particular, renal and
      cardiovascular dysfunction significantly increase the odds for death. Hence,
      systematic screening for organ dysfunction is advocated in cats with sepsis.

PMID- 30099964
TI  - Bleeding risk and complications associated with percutaneous ultrasound-guided
      liver biopsy in cats.
AB  - Objectives Liver biopsy is necessary for a diagnosis of liver disease; however,
      post-biopsy bleeding is a concern. The aim of this study was to describe the
      extent of bleeding and the occurrence of complications after percutaneous
      ultrasound-guided liver biopsy (PUGLB) in cats. Methods The medical records of 30
      cats that had a PUGLB were retrospectively reviewed. Using human guidelines,
      bleeding was classified as minor or major when the absolute change in packed cell
      volume (DeltaPCV) was >0 and <-6% or >=-6%, respectively. Complications were
      defined as physiologic compromise necessitating an intervention, or death. The
      relationship between DeltaPCV and the occurrence of complications and the
      signalment, initial PCV, coagulation parameters, serum liver enzymes and
      bilirubin, number of biopsies, histological diagnosis, ultrasound findings,
      radiologist experience, concurrent procedures and vitamin K administration were
      assessed using Fisher's exact test, ANOVA and Pearson's correlation coefficient,
      with a P value <0.05 considered significant. Results All cats had a decrease in
      PCV after biopsy. The mean DeltaPCV was -6.9% +/- 4.1%. Minor and major bleeding
      occurred in 13/30 (43.3%) and 17/30 (56.7%) cats, respectively, and non-lethal
      bleeding complications in 5/30 (16.7%). Cats with complications had a lower pre
      biopsy PCV ( P <0.003). Major bleeding was more likely with a diagnosis of
      hepatic lipidosis ( P = 0.03). There was no correlation between DeltaPCV or
      complications and signalment, coagulation parameters, serum parameters, number of
      biopsies, ultrasound findings, radiologist experience, concurrent procedures and
      vitamin K administration. Conclusions and relevance A PUGLB is a relatively safe
      procedure in cats, although many cats have a subclinical decrease in PCV. As
      conventional coagulation tests did not predict complications or the magnitude of
      DeltaPCV, there is a need for more sensitive indicators of bleeding risk in cats
      undergoing PUGLB.

PMID- 30099965
TI  - Field study assessing the performance of a patient-side blood test to determine
      neuter status in female cats based on detection of luteinising hormone.
AB  - Objectives The aim of this study was to assess the performance of a patient-side
      blood test in determining neuter status in female cats. Methods Residual blood
      samples from female cats of unknown neuter status that were admitted to four cat
      adoption centres in the UK were tested for luteinising hormone (LH) using the
      Witness LH test (Zoetis). A positive LH test result indicated that the cat was
      neutered. Cats were assessed for evidence of a surgical scar suggestive of prior
      neutering; if none was found, an exploratory laparotomy was performed to confirm
      neuter status. The LH test performance was assessed (sensitivity, specificity,
      negative and positive predictive value). Results Two hundred and thirty-six cats
      had both LH test and exploratory laparotomy data. The specificity of the test in
      detecting neutered cats was 100% (95% confidence interval 96.2-99.9) and the
      sensitivity was 69% (95% confidence interval 59.3-76.8). The prevalence of
      neutered cats in this sample was 49%. The positive and negative predictive values
      were 1 and 0.77, respectively. Conclusions and relevance The Witness LH test
      correctly detected all unneutered cats and thus there were no false positive
      results that incorrectly indicated a cat was neutered. This study therefore
      suggests that positive LH test results avoid the need to perform surgery to
      confirm neuter status. This has significant welfare benefits for cats as it
      provides a lower risk, faster and less traumatic alternative to surgery and, in
      the shelter setting, it will have a positive impact on the cost, speed of
      assessment and time to rehoming of cats.

PMID- 30099966
TI  - Transfer RNA function and evolution.

PMID- 30099967
TI  - Using focused pharmacovigilance for ensuring patient safety against
      antileishmanial drugs in Bangladesh's National Kala-azar Elimination Programme.
AB  - BACKGROUND: Adverse effects of antileishmanial drugs can affect patients' quality
      of life and adherence to therapy for visceral leishmaniasis (VL) and post-kala
      azar dermal leishmaniasis (PKDL). In Bangladesh, there are 26 treatment centers
      that manage leishmaniasis cases coming from 100 endemic upazilas (subdistricts)
      of 26 districts (these include VL, PKDL, treatment failure, and relapse VL and
      cutaneous leishmaniasis cases). This study aimed to investigate the feasibility
      of using focused pharmacovigilance for VL (VLPV) in Bangladesh's National Kala
      azar Elimination Programme for the early detection and prevention of expected and
      unexpected adverse drug reactions (ADRs). METHODS: This activity has been going
      on since December 2014. Activity area includes secondary public hospital or
      Upazila health complex (UHC) in hundred sub districts and Surya Kanta Kala-azar
      Research Center (SKKRC) in Mymensingh District, a specialized center for
      management of complicated VL and PKDL cases. Communicable Disease Control (CDC)
      of the Directorate General of Health Services (DGHS) assigned twenty five of
      hundred UHCs and SKKRC (total 26) as treatment centers depending on their
      suitable geographical location. This was implemented for better management of VL
      cases with Liposomal Amphotericin B (AmBisome(r)) to ensure patient convenience
      and proper utilization of this expensive donated drug. A VLPV expert committee
      and a UHC VLPV team were established, an operational manual and pharmacovigilance
      report forms were developed, training and refresher training of health personnel
      took place at UHCs and at the central level, collected information such as
      patient data including demographics, treatment history and response, adverse
      events were analyzed. This report includes information for the period from
      December 2014 to December 2016. RESULTS: From December 2014 to December 2016,
      1327 leishmaniasis patients were treated and 1066 (80%) were available for VLPV.
      Out of these, 57, 33, 9, and 1% were new VL, PKDL, VL relapse, and other cases,
      respectively. Liposomal amphotericin B was mostly used (82%) for case management,
      followed by miltefosine (20%) and paromomycin (3%). Out of the 1066 patients, 26%
      experienced ADRs. The most frequent ADR was fever (17%, 176/1066), followed by
      vomiting (5%, 51/1066). Thirteen serious adverse events (SAEs) (eight deaths and
      five unexpected SAEs) were observed. The expert committee assessed that three of
      the deaths and all unexpected SAEs were possibly related to treatment. Out of the
      five unexpected SAEs, four were miltefosine-induced ophthalmic complications and
      the other was an AmBisome(r)-induced avascular necrosis of the nasal alae. The
      Directorate General of the Drug Administration entered the ADRs into the World
      Health Organization Uppsala Monitoring Centre (WHO-UMC) VigiFlow database.
      CONCLUSIONS: This study found that VLPV through NKEP is feasible and should be
      continued as a routine activity into the public health system of Bangladesh to
      ensure patient safety against anti-leishmanial drugs.

PMID- 30099969
TI  - How do pig farms maintain low Salmonella prevalence: a case-control study.
AB  - Salmonella prevalence in UK pigs is amongst the highest in Europe, highlighting
      the need to investigate pig farms which have managed to maintain a low Salmonella
      seroprevalence. A total of 19 pig farms that had a consistently low (<10%)
      seroprevalence over 4 years (named Platinum farms) were compared against 38
      randomly selected Control farms, chosen to match the same distribution of
      production types and geographical distribution of the Platinum farms. Each farm
      was visited and floor faeces and environmental samples were collected. It was
      shown that Control farms had a significantly higher median percentage of pooled
      faecal samples positive for Salmonella compared with the Platinum farms (12.1%
      and 0.4% for pooled faecal samples, respectively) and were more likely to have
      serovars of public health importance detected (S. Typhimurium/ monophasic
      variants or S. Enteritidis). Considering the comprehensive on-farm sampling, the
      identification of farms negative for Salmonella, along with the identification of
      those that had maintained low prevalence over a long period is important. The
      risk factor analyses identified pelleted feed, feed deliveries crossing farm
      perimeter and regular antibiotic use as associated with being a Control farm.
      Performance data indicated that Platinum farms were performing better for
      slaughter live weight than Controls. Limited assessments of available pig
      movement records suggested that the source of pigs was not key to Platinum
      status, but further study would be needed to confirm this finding. These results
      emphasise that maintaining very low prevalence on UK farms is achievable.

PMID- 30099970
TI  - The management of laryngeal lipoid proteinosis.
AB  - BACKGROUND: Lipoid proteinosis is a rare autosomal recessive disorder caused by
      mutations in the extracellular matrix protein 1 gene. It is characterised by
      deposition of hyaline material in the skin and mucous membranes. This paper
      describes the management of two cases with laryngopharyngeal disease. METHODS:
      Two patients with a biopsy diagnosis of lipoid proteinosis were identified from
      the surgical pathology archive covering the period 2004-2016. Their notes were
      reviewed. RESULTS: An adult male and an adult female were identified. Both had
      dysphonia and laryngopharyngeal lesions. The patients underwent interval laser
      microlaryngoscopy to debulk disease but minimise mucosal injury and scarring,
      using a 'pepper pot' technique. Both had adequate symptom control. CONCLUSION:
      Lipoid proteinosis is a rare genetic condition, which typically presents in
      infancy with dysphonia and subsequent skin involvement. Two cases are presented
      to demonstrate that laryngotracheal symptoms can be controlled with interval
      laser debulking and the 'pepper pot' technique without causing stenosis.

PMID- 30099968
TI  - Real-world data reveal a diagnostic gap in non-alcoholic fatty liver disease.
AB  - BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of
      liver disease worldwide. It affects an estimated 20% of the general population,
      based on cohort studies of varying size and heterogeneous selection. However, the
      prevalence and incidence of recorded NAFLD diagnoses in unselected real-world
      health-care records is unknown. We harmonised health records from four major
      European territories and assessed age- and sex-specific point prevalence and
      incidence of NAFLD over the past decade. METHODS: Data were extracted from The
      Health Improvement Network (UK), Health Search Database (Italy), Information
      System for Research in Primary Care (Spain) and Integrated Primary Care
      Information (Netherlands). Each database uses a different coding system.
      Prevalence and incidence estimates were pooled across databases by random-effects
      meta-analysis after a log-transformation. RESULTS: Data were available for
      17,669,973 adults, of which 176,114 had a recorded diagnosis of NAFLD. Pooled
      prevalence trebled from 0.60% in 2007 (95% confidence interval: 0.41-0.79) to
      1.85% (0.91-2.79) in 2014. Incidence doubled from 1.32 (0.83-1.82) to 2.35 (1.29
      3.40) per 1000 person-years. The FIB-4 non-invasive estimate of liver fibrosis
      could be calculated in 40.6% of patients, of whom 29.6-35.7% had indeterminate or
      high-risk scores. CONCLUSIONS: In the largest primary-care record study of its
      kind to date, rates of recorded NAFLD are much lower than expected suggesting
      under-diagnosis and under-recording. Despite this, we have identified rising
      incidence and prevalence of the diagnosis. Improved recognition of NAFLD may
      identify people who will benefit from risk factor modification or emerging
      therapies to prevent progression to cardiometabolic and hepatic complications.

PMID- 30099971
TI  - Mixed motivations to provide formal care to older adults: lessons from a training
      program.
AB  - : ABSTRACTObjective:With the aging of the population, the demand for long-term
      services is increasing accordingly and the recruitment of paid caregivers to
      older adults has become a critical issue. Hence, there is a great need to train
      people in the care of older adults. This study examined motivations to
      participate in a new program, which aims to train young people (ages 19-25) to
      become paid caregivers for older adults. METHODS: The study is based on focus
      groups with program participants (N = 33) and on phone interviews with former
      participants (N = 8) and face-to-face interviews with staff members (N = 14).
      Transcripts were analyzed using qualitative content analysis. RESULTS: Three
      major themes emerged: (1) "Motivations to participate in the program," referred
      to participants' motivations to work with older adults. (2) "Reduced motivations
      due to ambiguity of roles," referred to the unclear definition of the care
      worker's role, which created a decrease in participants' motivations to provide
      care. (3) "Inadequate financial compensation," concerned participants' reduced
      motivation to participate in the program as a result of financial promises that
      were not realized. CONCLUSIONS: Findings suggest that it is important to be
      cautious about the motivations for participation in the program because by
      emphasizing the difficult situation of older adults, one stresses the low status
      assigned to older adults, rather than positive attributes. It is also suggested
      that care workers should be financially rewarded, so that despite the
      difficulties that may arise during work, they will feel valued and will want to
      remain in the profession.

PMID- 30099972
TI  - Depression is associated with self-rated frailty in older adults from an
      outpatient clinic: a prospective study.
AB  - : ABSTRACTObjectives:The aim of the present study was to evaluate the association
      between depression and SSRI monotherapy and frailty both baseline and
      prospectively in older adults. DESIGN: Prospective cohort study, 12-month follow
      up. SETTING: Geriatric outpatient clinic in Sao Paulo, Brazil. PARTICIPANTS: A
      total of 811 elderly adults aged 60 or older. MEASUREMENTS: Depression was
      diagnosed as follows: (1) a diagnosis of major depression disorder (MDD)
      according to DSM-5; or (2) an incomplete diagnosis of MDD, referred to as minor
      or subsyndromic depression, plus Geriatric Depression Scale 15-itens >= 6 points,
      and social or functional impairment secondary to depressive symptoms and observed
      by relatives. Frailty evaluation was performed through the FRAIL questionnaire,
      which is a self-rated scale. Trained investigators blinded to the baseline
      assessment conducted telephone calls to evaluate frailty after 12-month follow
      up. The association between depression and the use of SSRI with frailty was
      estimated through a generalized estimating equation adjusted for age, gender,
      total drugs, and number of comorbidities. RESULTS: Depression with SSRI use was
      associated with frailty at baseline (OR 2.82, 95% CI = 1.69-4.69) and after 12
      months (OR 2.75, 95% CI = 1.84-4.11). Additionally, depression with SSRI
      monotherapy was also associated with FRAIL subdomains Physical Performance (OR
      1.99, 95% CI = 1.29-3.07) and Health Status (OR 4.64, 95% CI = 2.11-10.21). SSRI
      use, without significant depressive symptoms, was associated with subdomain
      Health Status (OR 1.52, 95% CI = 1.04-2.23). CONCLUSION: It appears that
      depression with SSRI is associated to frailty, and this association cannot be
      explained only by antidepressant use.

PMID- 30099973
TI  - The "Golden Angels": effects of trained volunteers on specialling and readmission
      rates for people with dementia and delirium in rural hospitals.
AB  - : ABSTRACTObjectives:Evaluate the clinical outcomes for patients with dementia,
      delirium, or at risk for delirium supported by the person-centered volunteer
      program in rural acute hospitals. DESIGN: A non-randomized, controlled trial.
      PARTICIPANTS: Older adults admitted to seven acute hospitals in rural Australia.
      Intervention (n = 270) patients were >65 years with a diagnosis of dementia or
      delirium or had risk factors for delirium and received volunteer services.
      Control (n = 188) patients were admitted to the same hospital 12 months prior to
      the volunteer program and would have met eligibility criteria for the volunteer
      program, had it existed. INTERVENTION: Trained volunteers provided 1:1 person
      centered care with a focus on nutrition and hydration support, hearing and visual
      aids, activities, and orientation. MEASURES: Medical record audits provided data
      on volunteer visits, diagnoses, length of stay (LOS), behavioral incidents,
      readmission, specialling, mortality, admission to residential care, falls,
      pressure ulcers, and medication use. RESULTS: Across all sites, there was a
      significant reduction in rates of 1:1 specialling and 28 day readmission for
      patients receiving the volunteer intervention. LOS was significantly shorter for
      the control group. There were no differences in other patient outcomes for the
      intervention and control groups. CONCLUSION: The volunteer intervention is a
      safe, effective, and replicable way to support older acute patients with
      dementia, delirium, or risk factors for delirium in rural hospitals. Further
      papers will report on cost effectiveness, family carer, volunteer, and staff
      experiences of the program.

PMID- 30099974
TI  - Does phonological distance impact quality of phonological representations?
      Evidence from Arabic diglossia.
AB  - The study tested the impact of the phonological distance between Spoken Arabic
      (SpA) and Standard Arabic (StA) on quality of phonological representations among
      kindergarten, first-, second-, and sixth-grade Arabic-speaking children (N =
      120). A pronunciation accuracy judgment task targeted three types of StA words
      that varied in extent of phonological distance from their form in SpA: (a)
      identical words, with an identical lexical-phonological form in StA and SpA; (b)
      cognate words, with partially overlapping phonological forms; items in this
      category varied in degree of phonological distance too; and (c) unique words with
      entirely different lexical-phonological forms. Multilevel Regression analysis
      showed that phonological distance had a significant impact on quality of
      phonological representations across all grades. Growth in quality of phonological
      representations was mainly noted between the three younger groups and the sixth
      graders. Implications for the impact of phonological distance on phonological
      representations and on language and literacy development are discussed.

PMID- 30099975
TI  - Emerging outbreaks associated with conflict and failing healthcare systems in the
      Middle East.
AB  - The escalating conflicts in the Middle East have been associated with the rapid
      collapse of the existing healthcare systems in affected countries. As millions of
      refugees flee their countries, they become vulnerable and exposed to communicable
      diseases that easily grow into epidemic crises. Here, we describe infectious
      disease epidemics that have been associated with conflicts in the Middle East,
      including cholera, poliomyelitis, measles, cutaneous leishmaniasis, and
      diphtheria, that call for appropriate preventive measures. Local ongoing wars and
      failing healthcare systems have resulted in regional and global health threats
      that warrant international medical interventions.

PMID- 30099977
TI  - Predictors of finance management in dementia: managing bills and taxes matters.
AB  - : ABSTRACTObjectives:Finance management skills deteriorate early on in dementia,
      and can influence the ability to maintain control over personal affairs. The aim
      of this study was to assess the contributions of different types of cognition and
      motor functioning to finance management. DESIGN: Cross-sectional analysis using
      secondary data. SETTING: Community living. PARTICIPANTS: Baseline data from the
      Uniform Data Set from the National Alzheimer's Coordinating Centers were obtained
      and extracted up until December 2016. MEASUREMENTS: Measures on everyday
      functioning (Functional Assessment Questionnaire) and cognition (memory,
      executive functioning, and language), the Clinical Dementia Rating scale, and
      questions on Parkinsonian motor symptoms (gait disturbance, falls, tremors, and
      slowness) were included. Data were analyzed using bivariate correlation and
      linear regression analyses. RESULTS: A total of 9,383 participants were included
      in the analysis (Alzheimers disease (AD) = 8,201; behavioral variant fronto
      temporal dementia (bvFTD) = 796; Dementia with Lewy Bodies (DLB) = 386).
      Cognition and motor functioning varied significantly across AD, bvFTD, and DLB,
      with poorer motor functioning and poorer finance management skills in DLB than in
      AD and bvFTD. In the regression models, slowness, verbal fluency, executive
      functioning, and language, followed by age, gender, and diagnosis accounted for
      13.8% of the variation in managing bills, and for 11.4% of the variation in
      managing taxes. CONCLUSION: Maintaining finance management abilities for as long
      as possible is important for people with dementia, to avoid potential financial
      exploitation. Findings from this study highlight avenues to pursue to delay
      deterioration in managing bills and taxes, and help maintain financial control.

PMID- 30099976
TI  - The shift in seasonality of legionellosis in the USA.
AB  - According to the Centers for Disease Control and Prevention (CDC), from 2000 to
      2014, reported cases of legionellosis per 100 000 population increased by 300% in
      the USA, although reports on disease seasonality are inconsistent. Using two
      national databases, we assessed seasonal patterns of legionellosis in the USA. We
      created a monthly time series from 1993 to 2015 of reported cases of
      legionellosis from the CDC, and from 1997 to 2006 of medical claims of
      legionellosis-related hospitalisation in older adults from the Centers for
      Medicaid and Medicare Services (CMS). We split the study time interval into two
      segments (before and after 2003), and applied a Poisson harmonic regression model
      to each dataset and each segment. The time series of monthly counts exhibited a
      significant shift of seasonal peaks from mid-September (9.676 +/- 0.164 months)
      before 2003 to mid-August (8.452 +/- 0.042 months) after 2003, along with an
      alarming increase in the amplitude of seasonal peaks in both CDC and CMS data.
      The lowest monthly reported cases of legionellosis in 2015 (281) exceed the
      maximum value reported before 2003 (206). We also observed a discrepancy between
      CDC and CMS data, suggesting that not all cases of legionellosis diagnosed by
      hospital-based laboratories were reported to the CDC. Improved reporting of
      legionellosis is required to better inform the public and organise disease
      prevention.

PMID- 30099978
TI  - Removal of external ear canal exostoses by piezo surgery: a novel technique.
AB  - BACKGROUND: External auditory canal exostoses are known to occur in patients who
      engage in cold-water sports. Although the majority of patients with exostosis
      remain asymptomatic, larger lesions can cause wax impaction, conductive hearing
      loss and predispose to recurrent otitis externa. OBJECTIVE: A novel technique is
      described of using a piezo saw to excise exostoses that are symptomatic. The
      piezo saw is used to perform various procedures, but its use in removing
      exostoses has not been described in the literature. CONCLUSION: Excision of
      exostoses of the ear canal using a piezo saw is a safe technique and patients
      have a speedy recovery. This paper describes a new technique for removing
      exostoses.

PMID- 30099979
TI  - Association of depression with mortality in an elderly treated hypertensive
      population.
AB  - : ABSTRACTBackground:Both elevated blood pressure and/or depression increase the
      risk of cardiovascular disease and mortality. This study in treated elderly
      hypertensive patients explored the incidence of depression, its association (pre
      existing and incident) with mortality and predictors of incident depression.
      METHODS: Data from 6,083 hypertensive patients aged >=65 years enrolled in the
      Second Australian National Blood Pressure study were used. Participants were
      followed for a median of 10.8 years (including 4.1 years in-trial) and classified
      into: "no depression," "pre-existing" and "incident" depression groups based on
      either being "diagnosed with depressive disorders" and/or "treated with an anti
      depressant drug" at baseline or during in-trial period. Further, we redefined
      "depression" restricted to presence of both conditions for sensitivity analyses.
      For the current study, end-points were all-cause and any cardiovascular
      mortality. RESULTS: 313 (5%) participants had pre-existing depression and a
      further 916 (15%) participants developed depression during the trial period
      (incidence 4% per annum). Increased (hazard-ratio, 95% confidence-interval) all
      cause mortality was observed among those with either pre-existing (1.23, 1.01
      1.50; p = 0.03) or incident (1.26, 1.12-1.41; p < 0.001) depression compared to
      those without. For cardiovascular mortality, a 24% increased risk (1.24, 1.05
      1.47; p = 0.01) was observed among those with incident depression. The
      sensitivity analyses, using the restricted depression definition showed similar
      associations. Incident depression was associated with being female, aged >=75
      years, being an active smoker at study entry, and developing new diabetes during
      the study period. CONCLUSIONS: This elderly cohort had a high incidence of
      depression irrespective of their randomised antihypertensive regimen. Both pre
      existing and incident depression were associated with increased mortality.

PMID- 30099980
TI  - Dimethylated histone H3 lysine 9 is dispensable for the interaction between
      developmental pluripotency-associated protein 3 (Dppa3) and ten-eleven
      translocation 3 (Tet3) in somatic cells.
AB  - Both developmental pluripotency-associated protein 3 (Dppa3/Stella/PGC7) and
      dioxygenase ten-eleven translocation 3 (Tet3) are maternal factors that regulate
      DNA methylation reprogramming during early embryogenesis. In the mouse zygote,
      dimethylated histone H3 lysine 9 (H3K9me2) attracts Dppa3 to prevent Tet3
      mediated oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC).
      Here, we addressed the interplay between Dppa3 and Tet3 or H3K9me2 in somatic
      cells. In mouse NIH3T3 cells, the exogenously expressed Dppa3 preferentially
      accumulated in the cytoplasm and had no effect on Tet3-mediated 5hmC generation.
      In HeLa cells, the expressed Dppa3 was predominantly localised in the nucleus and
      could partially suppress Tet3-induced 5hmC accumulation, but this suppressive
      function was not correlated with H3K9me2. Co-immunoprecipitation assays further
      revealed an interaction of Dppa3 with Tet3 but not with H3K9me2 in HeLa cells. In
      cloned zygotes from somatic cells, Dppa3 distribution and 5hmC accumulation in
      nuclei were not affected by H3K9me2 levels. Taken together, these results suggest
      that H3K9me2 is not functionally associated with Dppa3 and Tet3 in somatic cells
      or somatic cell cloned embryos.

PMID- 30099981
TI  - Primary care redesign for person-centred care: delivering an international
      generalist revolution.
AB  - Person-centred primary care is a priority for patients, healthcare practitioners
      and health policy. Despite this, data suggest person-centred care is still not
      consistently achieved - and indeed, that in some areas, care may be worsening.
      Whole-person care is the expertise of the medical generalist - an area of
      clinical practice that has been neglected by health policy for some time. It is
      internationally recognised that there is a need to rebalance specialist and
      generalist primary care. Drawing on 15 years of scholarship within the science of
      medical generalism (the expertise of whole-person medical care), this discussion
      paper outlines a three-tiered approach to primary care redesign; describing
      changes needed at the level of the consultation, practice set up and strategic
      planning. The changing needs of patients living with complex chronic illness has
      already started a revolution in our understanding of healthcare systems. This
      paper outlines work to support that paradigm shift from disease-focused to person
      focused primary healthcare.

PMID- 30099982
TI  - Artificial blastocyst collapse prior to vitrification significantly improves
      Na+/K+-ATPase-dependent post-warming blastocoel re-expansion kinetics without
      inducing endoplasmic reticulum stress gene expression in the mouse.
AB  - Blastocoel expansion during embryo development is known to be reliant on the
      Na+/K+-ATPase pump, but little is known about the relative contribution of active
      (Na+/K+-ATPase pump) and facilitated diffusion (aquaporins) water transport
      during blastocoel re-expansion after vitrification. The aims of this study were
      to examine potential effects of artificial blastocoel collapse (ABC) on markers
      of embryo stress and the contribution of active and facilitated diffusion water
      transport mechanisms to blastocoel re-expansion. Day 5 mouse embryos were
      vitrified using either a standard protocol, laser pulse ABC, a hyperosmotic
      sucrose ABC protocol or both laser pulse and sucrose. Using real-time polymerase
      chain reaction, no differences were found in the gene expression of the
      endoplasmic reticulum (ER) stress markers activating transcription factor 4
      (Atf4) or heat shock protein 90-alpha (Hsp90alpha) 2 h after warming. Similarly,
      expression of the Na+/K+-ATPase pump gene, ATPase, Na+/K+ transporting, beta 1
      polypeptide (Atp1b1) and protein did not differ between groups. Aquaporin 8
      (Aqp8) gene expression was significantly lower in the laser + sucrose ABC group
      than in fresh controls, and aquaporin 3 (Aqp3) expression significantly higher in
      standard vitrified embryos compared with all other groups. Ouabain, a potent and
      specific Na+/K+-ATPase pump inhibitor, inhibited blastocoel re-expansion in both
      standard protocol- and laser ABC-vitrified embryos, reducing both groups to the
      same rate of re-expansion 3 h after warming. These results demonstrate that ABC
      before vitrification does not alter mRNA or protein expression of Na+/K+-ATPase,
      or mRNA levels of ER stress genes Atf4 and Hsp90alpha. Activity of the pump may
      be increased in ABC embryos, with potential compensation by AQP3 when it is
      compromised.

PMID- 30099983
TI  - Differential relationship between colorectal cancer and diabetes in a nationally
      representative sample of adults.
AB  - BACKGROUND: Diabetes has been identified as a risk factor for developing
      colorectal cancer (CRC); however, the literature identifying groups most at risk
      is sparse. This study aims to understand the relationship between CRC and
      diabetes by age and race/ethnicity. METHODS: This is a cross-sectional study of
      data from the 2001-2014 National Health and Nutrition Examination Survey
      (unweighted n = 37,173; weighted n = 214,363,348). Individuals were categorized
      as having CRC if diagnosed with colon or rectal cancer and as having diabetes if
      told by a doctor they had diabetes, were taking insulin, or had an HbA1c >= 6.5%.
      Covariates included gender, age, race, marital status, educational level and
      income as a ratio of the poverty line. Multivariable logistic regression was used
      to assess the relationship between CRC and diabetes overall and stratified by age
      and by race. RESULTS: 24.32% of the sample with CRC also had diabetes. After
      adjusting for covariates, individuals with diabetes had a 47% greater probability
      of having CRC (p = 0.03). While significance did not persist after stratification
      for those >=65 years (OR = 1.06, p = 0.74), those <65 years with diabetes had
      nearly 5-times higher odds of having CRC (OR = 4.78, p < 0.001). When stratified
      by race, both groups had statistically higher odds of having CRC; however, the
      odds for non-whites (OR = 1.87, p = 0.04) were higher compared to whites (OR =
      1.54, p = 0.03). CONCLUSION: Individuals younger than 65 and racial/ethnic
      minorities have higher odds of CRC when also diagnosed with diabetes. Targeted
      interventions for these populations, especially regarding screening
      recommendations, may result in earlier detection of CRC and improved health
      outcomes.

PMID- 30099984
TI  - Changes in platelet morphology indices in relation to duration of disease and
      glycemic control in children with type 1 diabetes mellitus.
AB  - BACKGROUND: There is limited data on platelet alterations in children with type 1
      diabetes mellitus (T1DM). We planned to study the effect of glycemic control and
      duration of T1DM on platelet morphology in children with T1DM. METHODS: We
      conducted an observational study on 260 children; 130 with T1DM (cases) and 130
      healthy controls, in a tertiary care pediatric hospital. Platelet indices
      including Platelet count (PLT), Mean Platelet Volume (MPV), Platelet Distribution
      Width (PDW), Platelet-Large cell ratio (P-LCR), Plateletcrit (PCT) were measured,
      and their means were compared between cases and controls and various subgroups
      among the cases. RESULTS: The MPV, PDW and P-LCR were significantly higher (p <
      0.05) in cases when compared to controls and in children with suboptimal glycemic
      control compared to optimal control. PLT was considerably lower in cases compared
      to controls. In children with new-onset T1DM, only PDW was significantly raised
      when compared to controls. MPV and P-LCR had a significant positive correlation
      with duration of T1DM. CONCLUSIONS: Children with T1DM have altered morphological
      parameter(s) which progress over time. Poor glycemic control is a significant
      risk factor for abnormal platelet indices.

PMID- 30099985
TI  - Skin autofluorescence is associated with vascular complications in patients with
      type 2 diabetes.
AB  - AIMS: Tissue accumulatedadvanced glycation end products (AGEs) can be evaluated
      non-invasively by an autofluorescence reader as skin autofluorescence (skin
      AF).The present study investigated whether skin AF is associated with diabetic
      micro- and macroangiopathies in Japanese patients with type 2 diabetes mellitus
      (T2DM). METHODS: Skin AF was measured in 193 enrolled Japanese patients with T2DM
      and 24 enrolled healthy non-diabetic subjects by using the AGE reader(r).
      Diabetic micro- and macroangiopathies were evaluated in the T2DM patients.
      RESULTS: Skin AF was significantly increased in patients with T2DM than in age-
      and sex-matched non-diabetic controls (2.35 +/- 0.51 [mean +/- SD] and 1.91 +/-
      0.29, respectively, p = 0.001). In subjects with T2DM, skin AF was associated
      with age, pack-years of smoking, and eGFR (estimated glomerular filtration rate)
      independently. Skin AF was significantly increased in patients with diabetic
      retinopathy, neuropathy, nephropathy, and macroangiopathy than in those without
      them, and significantly associated with the number of diabetic complications.
      Moreover, skin AF was an independent predictor for diabetic retinopathy,
      neuropathy, and nephropathy but not macroangiopathy, after adjusting for major
      traditional risk factors. CONCLUSIONS: Skin AF is an independent predictor for
      diabetic retinopathy, neuropathy and nephropathy in Japanese patients with T2DM.

PMID- 30099986
TI  - Short-term Toxicity of High Dose Rate Brachytherapy in Prostate Cancer Patients
      with Inflammatory Bowel Disease.
AB  - AIMS: Inflammatory bowel disease (IBD) has historically been considered a risk
      factor for increased bowel toxicity in patients receiving pelvic external beam
      radiotherapy. The risk is reduced in intensity-modulated radiotherapy compared
      with three-dimensional conformal radiotherapy. The effect of brachytherapy has
      been less extensively researched. Despite the increased dose to the gross tumour
      volume and decreased dose to organs at risk, previous studies have recommended
      avoidance of low dose rate (LDR) brachytherapy in patients with IBD, due to
      increased bowel toxicity. We investigated the effect of high dose rate (HDR)
      brachytherapy in IBD. MATERIALS AND METHODS: Eleven IBD patients across four
      different sites (in the UK and Spain) who received HDR brachytherapy, between
      2012 and 2015, were followed for up to 12 months. Acute bowel and urinary
      toxicity data were collected and recorded. RESULTS: The median length of follow
      up was 6 months (range between 6 weeks and 12 months). Five patients had Crohn's
      disease and six patients had ulcerative colitis. Only one patient (with Crohn's
      disease) had active disease at the time of treatment. This patient reported no
      bowel toxicity. Of the remaining patients, two suffered grade 1 diarrhoea (at 6
      weeks and 6 months); three suffered grade 1 proctitis (at 6 weeks and 6 months).
      There was no grade >=2 bowel toxicity. The most severe toxicity was grade 2
      urinary frequency in one patient (at 6 weeks). DISCUSSION: This small,
      prospective case series suggests that, in the short term, HDR brachytherapy is
      safe and well tolerated in IBD patients. Therefore, IBD should not automatically
      disqualify patients from, at least, HDR brachytherapy. The reason why these
      results differ from previous LDR studies possibly reflects the benefit of inverse
      planning, which more readily achieves rectal dose constraints in HDR
      brachytherapy.

PMID- 30099987
TI  - Regulation of the Activity in the p53 Family Depends on the Organization of the
      Transactivation Domain.
AB  - Despite high sequence homology among the p53 family members, the regulation of
      their transactivation potential is based on strikingly different mechanisms.
      Previous studies revealed that the activity of TAp63alpha is regulated via an
      autoinhibitory mechanism that keeps inactive TAp63alpha in a dimeric
      conformation. While all p73 isoforms are constitutive tetramers, their basal
      activity is much lower compared with tetrameric TAp63. We show that the dimeric
      state of TAp63alpha not only reduces DNA binding affinity, but also suppresses
      interaction with the acetyltransferase p300. Exchange of the transactivation
      domains is sufficient to transfer the regulatory characteristics between p63 and
      p73. Structure determination of the transactivation domains of p63 and p73 in
      complex with the p300 Taz2 domain further revealed that, in contrast to p53 and
      p73, p63 has a single transactivation domain. Sequences essential for stabilizing
      the closed dimer of TAp63alpha have evolved into a second transactivation domain
      in p73 and p53.

PMID- 30099988
TI  - Structural Basis for MARK1 Kinase Autoinhibition by Its KA1 Domain.
AB  - The kinase associated-1 (KA1) domain is found at the C-terminus of multiple
      Ser/Thr protein kinases from yeast to humans, and has been assigned
      autoinhibitory, membrane-binding, and substrate-targeting roles. Here, we report
      the crystal structure of the MARK1 kinase/UBA domain bound to its autoinhibitory
      KA1 domain, revealing an unexpected interface at the alphaD helix and contacts
      with both the N- and C-lobes of the kinase domain. We confirm the binding
      interface location in kinetic studies of variants mutated on the kinase domain
      surface. Together with other MARK kinase structures, the data implicate that the
      KA1 domain blocks peptide substrate binding. The structure highlights the kinase
      specific autoinhibitory binding modes of different KA1 domains, and provides
      potential new avenues by which to intervene therapeutically in Alzheimer's
      disease and cancers in which MARK1 or related kinases are implicated.

PMID- 30099991
TI  - Reprint of "The relationship between culinary skills and eating behaviors:
      Challenges and opportunities for parents and families".
AB  - Unhealthy dietary intake among American children and adults is of great concern
      to public health practitioners, nutritional scientists, and child development
      experts. Cooking skills are related to healthier dietary intake among Americans
      of all ages, but remain a substantial barrier for many parents who want to serve
      healthy meals for their families at home. Culinary education interventions are
      effective solutions for many parents who do not know how to cook, but issues with
      participation bias mean that these programs are not effective solutions for all
      individuals. The food industry should develop solutions to help those parents for
      whom learning cooking skills is not an option - specifically through the
      development of healthier pre-assembled or prepared foods that do not require
      cooking skills to make. In the future, the research community should also strive
      to collect comprehensive population-based data on the state of cooking skills in
      the United States.

PMID- 30099990
TI  - Lipid Droplet Phase Transition in Freezing Cat Embryos and Oocytes Probed by
      Raman Spectroscopy.
AB  - Embryo and oocyte cryopreservation is a widely used technology for
      cryopreservation of genetic resources. One limitation of cryopreservation is the
      low tolerance to freezing observed for oocytes and embryos rich in lipid
      droplets. We apply Raman spectroscopy to investigate freezing of lipid droplets
      inside cumulus-oocyte complexes, mature oocytes, and early embryos of a domestic
      cat. Raman spectroscopy allows one to characterize the degree of lipid
      unsaturation, the lipid phase transition from the liquid-like disordered to solid
      like ordered state, and the triglyceride polymorphic state. For all cells
      examined, the average degree of lipid unsaturation is estimated as ~1.3 (with +/
      20% deviation) double bonds per acyl chain. The onset of the lipid phase
      transition occurs in a temperature range from -10 to +4 degrees C and does not
      depend on the cell type. Lipid droplets in cumulus-oocyte complexes are found to
      undergo abrupt lipid crystallization shifted in temperature from the ordering of
      the lipid conformational state. In the case of mature oocytes and early embryos
      obtained in vitro, the lipid crystallization is broadened. In the frozen state,
      lipid droplets inside cumulus-oocyte complexes have a higher content of
      triglyceride polymorphic beta and beta' phases than estimated for mature oocytes
      and early embryos. For the first time, to our knowledge, the temperature
      evolution of the phase state of lipid droplets is examined. Raman spectroscopy is
      proved to be a promising tool for in situ monitoring of the lipid phase state in
      a single embryo/oocyte during its freezing.

PMID- 30099989
TI  - Linear Chains of HER2 Receptors Found in the Plasma Membrane Using Liquid-Phase
      Electron Microscopy.
AB  - The spatial distribution of the human epidermal growth factor 2 (HER2) receptor
      in the plasma membrane of SKBR3 and HCC1954 breast cancer cells was studied. The
      receptor was labeled with quantum dot nanoparticles, and fixed whole cells were
      imaged in their native liquid state with environmental scanning electron
      microscopy using scanning transmission electron microscopy detection. The
      locations of individual HER2 positions were determined in a total plasma membrane
      area of 991 MUm2 for several SKBR3 cells and 1062 MUm2 for HCC1954 cells. Some of
      the HER2 receptors were arranged in a linear chain with interlabel distances of
      40 +/- 7 and 32 +/- 10 nm in SKBR3 and HCC1954 cells, respectively. The finding
      was tested against randomly occurring linear chains of six or more positions,
      from which it was concluded that the experimental finding is significant and did
      not arise from random label distributions. Because the measured interlabel
      distance in the HER2 chains is similar to the 36-nm helix-repetition distance of
      actin filaments, it is proposed that a linking mechanism between HER2 and actin
      filaments leads to linearly aligned oligomers.

PMID- 30099992
TI  - Combination of conventional culture, vial culture, and broad-range PCR of
      sonication fluid for the diagnosis of prosthetic joint infection.
AB  - We assessed the value of conventional culture, vial culture, and broad-range PCR
      of the sonication fluid (SF), individually or in combinations, for the diagnosis
      of prosthetic joint infection (PJI). We studied 114 consecutive patients (median
      age:72.5 years, males: 28.07%) undergoing removal of a total knee or hip
      prosthesis. By non-microbiologic criteria, 87 patients had aseptic failure, and
      27 PJI. All patients had periprosthetic tissue culture, sonication of prosthesis,
      and study of SF by conventional and vial culture, and PCR. Compared to tissue
      culture, each test was significantly more sensitive and less specific. If only
      one test was positive, the sensitivity was 88.46% and specificity 64.29%. If all
      three SF tests were positive, sensitivity, and NPV were decreasing (34.6% and
      80.23%), but specificity and PPV were increasing up to 98.57% and 90.9%,
      respectively, outperforming tissue culture. A triple negative test practically
      excluded PJI.

PMID- 30099993
TI  - [Impact of beauty and well-being care assessed in a national survey including
      1166 individuals].
AB  - INTRODUCTION: Research has suggested a high level of satisfaction following
      beauty and well-being care in oncology. We aimed to assess perception of beauty
      and well-being care in a large sample of patients affected by cancer. METHODS:
      From June through August, 2017, a physical and online survey was conducted
      recruiting patients affected by cancer and their relatives. A questionnaire,
      established in a collaborative manner with healthcare providers and patients,
      collected general demographic and medical data, awareness and knowledge data, the
      experience of beauty and well-being care and perceived benefits. RESULTS: At
      baseline, 1263 people were recruited (online, n=485; others, n=778) with 1254
      usable replies. After excluding caregivers (n=88), the analysis was made on 1166
      patients (mean age=51.7). This sample included 1080 women (92.6 %) and breast
      cancer was prominent (n=827; 70.9%). Among the 481 patients, who had received
      beauty and well-being care, 405 stated them as a relaxing time (84 %) and the
      average ranking was 8,1/10. Mean number of sessions was 2.8. A combined scheme of
      beauty and well-being care (individual and collective) and a greater number of
      sessions were statistically associated with a higher perceived benefit (P=0.02
      and P<0.001) and a higher level of recommendation (P=0.039 and P=0.05).
      DISCUSSION: This large national survey confirms the high level of satisfaction
      associated with beauty and well-being care. The type and number of sessions seem
      to be positively correlated with a greater benefit.

PMID- 30099994
TI  - Characterization of a novel cysteine-rich antifungal protein from Fusarium
      graminearum with activity against maize fungal pathogens.
AB  - Filamentous fungi are an invaluable source for biocontrol strategies and for
      production and development of different antifungal polypeptides. Within this
      context, cysteine-rich antifungal AFP-like peptides stand out among many
      different antimicrobial compounds given their production easiness, stability,
      versatility, and efficacy. AFP from Aspergillus giganteus represents the hallmark
      of this still increasing family of antifungal polypeptides. Close in silico
      analyses of the Fusarium graminearum genome revealed the presence of an AFP-like
      peptide, here designated as FgAFP. This new peptide was cloned, produced in the
      yeast Pichia pastoris, and characterized. The results obtained showed its strong
      and specific antifungal activity against several well-recognized maize pathogens,
      but inefficacy against F. oxysporum, which has not been described as a natural
      biological competitor of other fungal pathogens assayed. All results together
      suggest that this small peptide is an important factor for the fungal interplays
      involved in maize infection and reveals unforeseen potential biotechnological
      applications for FgAFP in maize production and storage.

PMID- 30099995
TI  - ESBL- and AmpC-producing Escherichia coli from legally and illegally imported
      meat: Characterization of isolates brought into the EU from third countries.
AB  - Multiresistant Enterobacteriaceae producing extended-spectrum beta-lactamases
      (ESBL) constitute a serious healthcare concern. Contaminated meat and meat
      products have been suggested as a major transmission route for these strains in
      the population. In this study, 36 ESBL-/AmpC-producing Escherichia (E.) coli
      isolates recovered from meat products imported into the EU from third countries
      (non-EU countries), both legally and illegally, were examined with regard to
      their antibiotic resistance profiles, virulence-associated genes and their
      genetic relatedness. The isolates were characterized by antibiotic susceptibility
      testing, multilocus sequence typing, macrorestriction analysis, microarray
      analyses and additional PCR assays. The most prevalent ESBL gene among the
      isolates was blaCTX-M-2 (n = 15), followed by the AmpC beta-lactamase gene blaCMY
      2 (n = 8). The remaining isolates carried genes belonging to CTX-M groups 8, 1 or
      9, or blaSHV-12. This distribution differs from the genotypes typically detected
      in meat-associated isolates of European origin. Most isolates showed additional
      phenotypic resistances and genes conferring resistance to further antimicrobial
      agents were detected through microarray analysis. Most commonly observed were
      resistances to tetracycline, sulfamethoxazole/trimethoprim, and gentamicin. A
      genotype conferring multidrug resistance to 3 or more classes of antimicrobials
      could be observed in 33 isolates (91.7%). Most isolates carried at least one gene
      associated with virulence and one isolate could be identified as an
      enteropathogenic E. coli, indicating a potential risk to consumers' health.
      Molecular typing results revealed a genetic variety among the isolates. The most
      common multilocus sequence types were ST101 and ST117, represented by three
      isolates each. One isolate belonged to ST131 and three novel sequence types could
      be identified among three isolates (ST7509, ST7602, ST7845). Group D was the most
      prevalent phylogenetic group, which was represented by 18 isolates. Overall, the
      results of this study show that imported meat products can constitute a source
      for locally uncommon lineages of multidrug resistant and virulent ESBL-producing
      E. coli and can thereby facilitate their dissemination in Europe.

PMID- 30099998
TI  - Hyperglycemia Syndromes.
AB  - Diabetes mellitus and its complications are among the leading causes of organ
      failure around the world. It is imperative that timely, patient-centered care is
      provided to avoid microvascular and macrovascular damage. People with well
      controlled diabetes can live long and healthy lives through interprofessional
      management, emphasizing optimal, individualized care.

PMID- 30099996
TI  - Characterization of Bacillus cereus group isolates from powdered food products.
AB  - Mashed potato powder as well as powdered infant formula (PIF) are frequently
      contaminated with Bacillus cereus sensu lato (B. cereus s.l.), mainly with its
      spores. These products have also been implicated in foodborne illnesses. Here, we
      characterized B. cereus s.l. isolates originating from powdered products based on
      sporulation assays, toxin gene profiling, and panC typing combined with a
      SplitsTree analysis. Furthermore, cytotoxicity assays with B. cytotoxicus
      isolates were performed. 78% of PIF tested positive for B. cereus s.l., whereas
      92% of all mashed potato powders were positive. In total, 43 isolates were
      further characterized. The nhe and cytK2 genes were most frequently detected.
      Moreover, a cereulide-producer was detected from PIF. Most isolates were assigned
      to panC group III, but members of group II, IV, V, and VII could also be found.
      Nine B. cytotoxicus were isolated out of nine mashed potato powders. All panC
      group VII isolates were positive for cytK1. Cytotoxicity assays of these nine
      isolates revealed one highly cytotoxic strain, while all other isolates exhibited
      no detectable cytotoxicity, underpinning that cytotoxicity of a certain B. cereus
      group strain cannot be deduced from the sole presence or absence of toxin genes.

PMID- 30099999
TI  - Immunosuppressive/Autoimmune Disorders.
AB  - Autoimmune disorders are a category of diseases in which the immune system
      attacks healthy cells as a result of a dysfunction of the acquired immune system.
      Clinical presentation and diagnosis are disease specific and often correspond
      with the degree of inflammation, as well as the systems involved. Treatment
      varies based on the specific disease, its stage of presentation, and patient
      symptoms. The primary goal of treatment is to decrease inflammation, minimize
      symptoms, and lessen the potential for relapse. Graves disease, Hashimoto
      thyroiditis, rheumatoid arthritis, Crohn disease, ulcerative colitis, systemic
      lupus erythematosus, and multiple sclerosis are discussed in this article.

PMID- 30100000
TI  - Fat Embolism Syndrome.
AB  - Fat embolisms are fat globules that enter the circulatory system, typically
      through trauma, that may or may not lead to the development of fat embolism
      syndrome (FES), a rare and ill-defined diagnosis that can cause multiorgan
      failure and death. The exact mechanism of FES remains unknown, although several
      theories support the involvement of inflammatory response activation that
      contributes to characteristic clinical findings. There is no gold standard for
      diagnosis of FES, and treatment at this time remains primarily supportive. Early
      recognition of FES symptoms is the most beneficial nursing intervention for
      combating this serious disorder.

PMID- 30099997
TI  - Beverage spoilage yeast detection methods and control technologies: A review of
      Brettanomyces.
AB  - Spoilage yeasts detection is the key to improve the quality of alcoholic
      fermentation beverages such as wine and cider. The metabolic activity of the
      spoilage yeast causes irreparable damage to many liters of final products every
      year. Therefore, winemakers and cider-house companies suffer a substantial
      economic impact. Thus, over the years, many detection techniques have been
      proposed to control the occurrence of spoilage yeast. Out of the many spoilage
      yeast genera, Brettanomyces is one of the most commonly encountered in the
      beverage industry. Leveraging its ability to thrive in wine and cider conditions
      (low pH, high levels of ethanol, and low oxygenation levels), Brettanomyces can
      proliferate inside beverage production tanks. Moreover, their resultant by
      products reduce the quality of the beverage. While the beverage industry has made
      great strides in detecting harmful organisms, gaps remain. Traditional methods
      such as microscopy, cell plating, gas chromatography-mass spectrometry, etc. are
      often imprecise, expensive, and/or complicated. New emerging spoilage yeast
      detection platforms, such as biosensors and microfluidic devices, aim to
      alleviate these constraints. Novel platforms have already demonstrated great
      promise to be a real alternative for in situ and fast detection in the beverage
      industry. Finally, the review discusses the potential of emerging spoilage yeast
      detection and treatment methods.

PMID- 30100001
TI  - Diagnosis and Treatment of Common Pain Syndromes and Disorders.
AB  - Management of chronic pain has become a significant challenge for primary care
      providers, and the population of patients with chronic pain is expected to
      increase. Common syndromes seen in the primary care setting include myofascial
      pain syndrome, fibromyalgia, chronic postsurgical pain, complex regional pain
      syndrome, and painful diabetic neuropathy. This article describes these syndromes
      and presents current treatment options.

PMID- 30100002
TI  - Malabsorption Syndromes.
AB  - Malabsorption syndrome refers to the small intestines' inability to absorb
      certain nutrients and fluids. There are several common associated disorders,
      which may present with subtle and/or overt symptoms. With subtle symptoms, it is
      difficult to determine the cause, making diagnosis difficult or even inaccurate.
      Malabsorption can originate from an immune response, an inflammatory process, or
      alternation of the small intestines by surgical methods. This article reviews
      common malabsorption disease processes of the small bowel and the resulting
      pathophysiology. Diagnostic studies, treatment, and prognosis of various
      conditions within the malabsorption disease state are discussed.

PMID- 30100003
TI  - An Overview of Munchausen Syndrome and Munchausen Syndrome by Proxy.
AB  - Munchausen syndrome and Munchausen syndrome by proxy are complex diseases that
      are difficult to diagnose and treat. To assist in this process, an overview of
      diagnostic criteria with common characteristics and red flags are discussed, with
      case studies illustrating identification and diagnosis of these disorders.
      Treatment options are addressed within the context of each of these complex
      syndromes. The provider's knowledge of diagnostic criteria and treatment options
      for Munchausen syndrome and Munchausen syndrome by proxy promotes better outcomes
      for patients. Without an early diagnosis and intervention, the patient is at high
      risk for severe complications, including organ failure and mortality.

PMID- 30100004
TI  - Evaluation and Treatment of Adrenal Dysfunction in the Primary Care Environment.
AB  - Adrenal insufficiency (Addison's disease) and Cushing's syndrome are rare
      disorders characterized by abnormal secretion of adrenal hormones. All patients
      with adrenal insufficiency and many with Cushing's syndrome require life-long
      therapy with the potential to impact the quality of life. Management requires
      gain of a significant amount of knowledge related to treatment, self-care, and
      how to react quickly in critical situations. Knowledge deficits related to
      management may cause patients to become critically ill and may even cause death.
      Ongoing patient/family teaching is crucial for proper disease management and
      sustaining the quality of life.

PMID- 30100005
TI  - Male and Female Hypogonadism.
AB  - Hypogonadism is a clinical syndrome that results in hormone deficiency in men and
      women. Primary hypogonadism is caused by gonadal (testicular or ovarian) failure.
      Secondary hypogonadism is the result of a dysfunction within the hypothalamus
      and/or pituitary. Diagnosis of hypogonadism requires a comprehensive health
      history, evaluation of the signs and symptoms, complete physical examination, as
      well as laboratory and diagnostic testing for both sexes. Hormone replacement is
      the hallmark of hypogonadism treatment. Restoring and/or maintaining quality of
      life is a major consideration in the management of patients with hypogonadism.

PMID- 30100006
TI  - Polycystic Ovary Syndrome.
AB  - Polycystic ovary syndrome (PCOS) is a commonly occurring endocrine disorder
      characterized by hirsutism, anovulation, and polycystic ovaries. Often comorbid
      with insulin resistance, dyslipidemia, and obesity, it also carries significant
      risk for the development of cardiovascular and metabolic sequelae, including
      diabetes and metabolic syndrome. Traditionally, the treatment of patients with
      PCOS has focused on relief of symptoms. Here, the criteria for the diagnosis of
      PCOS are reviewed with an emphasis on the stratification of subtypes by metabolic
      features. Then treatment options are reviewed according to the management goal:
      relief of hyperandrogenic symptoms, regulation of menstruation, and restoration
      of fertility.

PMID- 30100007
TI  - Chest Pain: If It Is Not the Heart, What Is It?
AB  - Noncardiac chest pain is an angina-type discomfort without indication of
      ischemia. Diagnosis can be difficult because of its heterogeneous nature.
      Classification varies by specialty; gastroenterology uses the terminology
      gastroesophageal reflux disease related versus non-gastroesophageal reflux
      disease related. Other disciplines recognize noncardiac chest pain etiologies as
      having gastrointestinal, musculoskeletal, psychiatric, or pulmonary/other as
      underlying etiologies. Diagnostics yield a specific cause for effective
      treatment, which is aimed at the underlying etiology, but it is not always
      possible. Some patients with noncardiac chest pain have comorbidities and ongoing
      pain that lead to decreased quality of life and continued health care use.

PMID- 30100008
TI  - Evaluation and Treatment of Restless Legs Syndrome in the Primary Care
      Environment.
AB  - Restless legs syndrome/Willis-Ekbon disease (RLS/WED) is a common sensorimotor
      disorder characterized by an irresistible urge to move and is associated with an
      uncomfortable sensation typically in the lower extremities. Dopaminergic
      neurotransmission abnormalities, genetics, sleep deprivation, and iron deficiency
      all play key roles in the pathogenesis of primary RLS. Secondary RLS has been
      associated with other medical conditions and medication usage. A thorough
      subjective evaluation and complete neurologic examination are key in the
      diagnosis of RLS/WED. Treatment includes pharmacologic and nonpharmacologic
      approaches. Referral to a neurologist or sleep specialist should be considered if
      initial treatment plans are ineffective.

PMID- 30100009
TI  - Degenerative or Debilitative Neurologic Syndromes.
AB  - Neurodegenerative disorders are progressive, debilitating impairments of
      neurologic function. Dementia affects cognition and function. Persons with
      cognitive deficits should undergo a full workup and may be treated with
      cholinesterase inhibitors and/or memantine. Behavioral and psychological symptoms
      of dementia may be assessed and treated individually. Parkinson disease is a
      disorder of movement. Levodopa is the standard treatment of dopamine-related
      movement symptoms. Associated symptoms should be assessed and treated. Other
      neurodegenerative syndromes are less common but highly debilitating. Currently,
      there are no curative or disease-modifying therapies for neurodegenerative
      disorders. Novel therapies or research are in the pipeline.

PMID- 30100010
TI  - Paroxysmal Sympathetic Hyperactivity Syndrome Following Traumatic Brain Injury.
AB  - Paroxysmal sympathetic hyperactivity (PSH) is a syndrome classified by episodic
      presentation of abnormal sympathetic and motor symptoms observed in patients with
      acquired brain injuries. Although the exact physiologic mechanism of PSH is not
      fully understood, its clinical significance has been well-established. PSH
      diagnosis depends on the identification of symptom presence, severity, and
      patterns. Treatment of PSH is rooted in pharmacologic management of targeted
      symptoms. Although complex, recognition and management of PSH has meaningful
      implications on the hospitalization and recovery trajectory for adult patients
      with traumatic brain injuries.

PMID- 30100011
TI  - Those Conditions You May Not Be Expecting.

PMID- 30100012
TI  - Cumulus cells of camel (Camelus dromedarius) antral follicles are multipotent
      stem cells.
AB  - The mammalian ovary is a highly dynamic organ, in which proliferation and
      differentiation occur constantly during the entire life span, particularly in
      camels that are characterized by a follicular wave pattern and induced ovulation.
      Granulosa cells are the main cells of mature follicles. Two distinct cell types,
      namely, the mural and cumulus granulosa cells are distinguished on the basis of
      antral fluid increase. The multipotency of follicular fluid and the luteinizing
      cell were recently demonstrated. However, reports regarding the plasticity of
      cumulus cells are lacking. We obtained cumulus cells from cumulus-oocyte
      complexes and showed that camel cumulus cells expressed stem cell mRNA
      transcripts (POU5A1, KLF4, SOX2, and MYC) and were able to differentiate into
      other non-ovarian follicular cell types in vitro, such as neurons, osteoblasts,
      and adipocytes. In contrast, removal of the ooplasm (oocytectemy) showed no
      effect on cumulus cell proliferation and differentiation. This is the first
      report to identify an invaluable source of multipotent stem cells, which is
      routinely discarded during in vitro embryo production. The plasticity and
      transdifferentiation capability of camel cumulus cells definitely requires
      attention as it provides a cheap biological experimental model for basic research
      in stem cells and for understanding ovarian differentiation, both of which are
      relevant for use in regenerative medicine and tissue engineering in humans and
      animals.

PMID- 30100014
TI  - Hexagonal boron nitride stationary phase for gas chromatography.
AB  - This work describes the separation performance of utilizing hexagonal boron
      nitride (h-BN) as the stationary phase for capillary gas chromatography (GC). The
      statically coated h-BN column showed moderate polarity and achieved column
      efficiencies of 3455 plates/m and 3800 plates/m for naphthalene and n-dodecane,
      respectively. With temperature-dependent structure properties, the h-BN
      stationary phase exhibited stronger retention for polycyclic aromatic
      hydrocarbons (PAHs) over phthalic acid esters (PAEs) and showed advantageous
      separation performance over the g-C3N4 and commercial polysiloxane stationary
      phases. Moreover, it displayed preferential retention for halogenated analytes
      and high resolution performance for structural and positional isomers. In
      addition, the h-BN column showed good column repeatability with relative standard
      deviation (RSD) values of 0.03%-0.07% for run-to-run, 0.31%-0.71% for day-to-day
      and 2.6%-5.3% for column-to-column, respectively, and thermal stability up to 260
      degrees C.

PMID- 30100013
TI  - Facile synthesis of magnetic covalent organic framework nanobeads and application
      to magnetic solid-phase extraction of trace estrogens from human urine.
AB  - A rapid and facile approach was developed for the synthesis of core-shell
      structured magnetic covalent organic framework nanobeads by using the
      monodisperse Fe3O4 nanoparticles (NPs) as magnetic core, and 1,3,5
      triformylbenzene (Tb) and benzidine (Bd) as two building blocks (denoted as
      Fe3O4@TbBd), which were explored as an adsorbent for magnetic solid-phase
      extraction (MSPE) of estrogens from human urine sample. The core-shell structured
      Fe3O4@TbBd nanobeads showed some attractive features involving high specific
      surface area (202.18 m2/g), uniform pore size distribution (2.8 nm), high
      magnetic responsivity (41.4 emu/g), as well as excellent thermal and chemical
      stability, which made it an ideal adsorbent for selective isolation and
      enrichment of estrogens. Some parameters influencing extraction efficiency,
      including adsorbent dosage, extraction time, pH, ion strength, desorption solvent
      and desorption time were investigated systematically. Combined with HPLC-MS, a
      simple, fast, and sensitive method was developed for the enrichment and sensitive
      determination of seven estrogens, which showed good linearity (r > 0.9978) in the
      range of 0.005-10 MUg/L, low limits of detection (0.2-7.7 ng/L, S/N = 3), low
      limits of quantification (0.6-25.6 ng/L, S/N = 10), high enrichment factors (75
      197 fold), and good precision with relative standard deviations (RSD) lower than
      4.8% for intra-day and 6.7% for inter-day. The proposed method was successfully
      applied to the analysis of trace estrogens in urine sample of pregnant woman with
      good recoveries (80.6-111.6%), demonstrating the promising potential of the
      Fe3O4@TbBd nanobeads as adsorbent in sample pretreatment.

PMID- 30100017
TI  - Myocardial Injury After Non-cardiac Surgery: What this "MINS" for the Vascular
      Surgeon?

PMID- 30100015
TI  - Modified binodal model describes phase separation in aqueous two-phase systems in
      terms of the effects of phase-forming components on the solvent features of
      water.
AB  - The binodal model pioneered by Guan et al. [Y. Guan, T. H. Lilley, T. E. Treffry,
      J. Chem. Soc. Faraday Trans., 89 (1993) 4283-4298] remains the most successful in
      regard to the quantitative description of phase diagrams among various
      theoretical models proposed to describe phase separation in aqueous mixtures of
      polymers. This is a semi-empirical model based on the assumption that any point
      on the binodal line may be viewed as a saturated solution of the phase-forming
      compound-1 in the solution of the phase-forming compound-2. Although this model
      is originally based on the excluded volume concept, we suggest that the
      solubility of the compound-1 in solutions of compound-2 may depend on the solvent
      properties of water in solutions of compound-2. The binodal model described in
      these terms was very successfully applied to the phase diagrams of aqueous two
      phase systems formed by different pairs of polymers (dextran, Ficoll,
      poly(ethylene glycol)-8000, and Ucon). Phase diagram of a new aqueous two-phase
      system formed by trimethylamine N-oxide (TMAO) and polypopylene glycol-400 and
      previously reported phase diagram for system formed by TMAO and poly(ethylene
      glycol)-600 were also described by this model quite well. It was found that the
      modified binodal model is also applicable to single polymer-salt and polymer
      ionic liquid aqueous two-phase systems. The most important conclusion of our
      study is that the effects of different compounds (polymers, salts, ionic liquids)
      on the solvent features of water in their aqueous solutions cause changes in the
      water structure, resulting in phase separation in the mixtures of these
      compounds.

PMID- 30100018
TI  - Endovascular Today: Give Me a Narrowing in the Venous System, and I Shall Stent
      It.

PMID- 30100016
TI  - Melamine-based porous organic polymers inline solid phase extraction coupled with
      high performance liquid chromatography for the analysis of phytohormones in juice
      samples.
AB  - A melamine-based porous organic polymer (mPMF) was synthesized as solid phase
      extraction (SPE) adsorbent for inline SPE-high performance liquid chromatography
      (HPLC)-ultraviolet detector (UV) analysis of five phytohormones. Melamine
      contributed to the rich pi-electron and N-containing triazine structure for mPMF,
      which could form pi-pi interaction and intermolecular hydrogen bond with COOH
      containing phytohormones. The synthesized mPMF adsorbent shows extremely high
      extraction efficiency for five target analytes (>80%) including salicylic acid,
      indole-3-acetic acid, abscisic acid, 2,4-dichlorophenoxyacetic acid and 1
      naphthalene acetic acid. The factors affecting extraction of the target
      phytohormones were investigated and the optimized experimental conditions were
      established. The linear range was 0.2-100 MUg/L with the limits of detection in
      the range of 0.06-0.11 MUg/L for five target phytohormones. The developed method
      of mPMF-inline-SPE-HPLC-UV was applied for the analysis of trace target
      phytohormones in tomato and grape juice samples, and the recovery in the range of
      83.1-116% and 87.2-121% was obtained for the spiked tomato and grape juice,
      respectively. This method has the advantages of high sensitivity and good
      reproducibility, and it has good application potential for the analysis of
      phytohormones in fruit samples. Moreover, inline analysis avoided the problems of
      sample pollution and sample loss, and provided a sample throughput of 5/h.

PMID- 30100019
TI  - Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents.
AB  - Continuous efforts have been made to discover new drugs for the treatment of
      Chagas' disease, human African trypanosomiasis, and leishmaniasis. We have
      previously reported the synthesis and antileishmanial and antitrypanosomal (Y
      strain) properties of 2,3-disubstituted quinoxalines. Considering their promising
      antiparasitic potential, the present study was conducted to expand our search and
      take advantage of high-throughput assays to investigate the effects of
      quinoxaline derivatives against Leishmania donovani, Trypanosoma brucei, and
      Trypanosoma cruzi (Tulahuen strain). These compounds were active against the
      kinetoplastid parasites that were evaluated. The 2-chloro-3
      methylsulfoxylsulfonyl and 2-chloro-3-methylsulfinyl quinoxalines were the most
      potent, and some of these derivatives were even more active than the reference
      drugs. Although the 2,3-diaryl-substituted quinoxalines were not active against
      all of the parasites, they were active against T. brucei and intracellular
      amastigotes of T. cruzi, without interfering with mammalian cell viability. These
      compounds presented encouraging results that will guide our future studies on in
      vivo bioassays towards the mode of action.

PMID- 30100020
TI  - Design and synthesis of novel pyrimido[5,4-d]pyrimidine derivatives as GPR119
      agonist for treatment of type 2 diabetes.
AB  - We described the discovery and optimization of a novel series of
      pyrimidopyrimidine derivatives as G-protein coupled receptor 119 (GPR119)
      agonists against type 2 diabetes. Most designed compounds displayed significant
      GPR119 agonistic activities. Optimized analogues 15a and 21e exhibited highly
      potent agonistic activities with single digit EC50 values (2.2 nM and 8.1 nM,
      respectively). Therefore, 15a and 21e were evaluated for their oral glucose
      tolerance test (oGTT) in C57BL/6N mice. Compound 15a reduced the blood glucose
      area of under curve from 0 to 2 h (AUC0-2h) to 13.5% at the dose of 15 mg/kg
      comparing with Metformin reduced 18% of AUC0-2h at the dose of 300 mg/kg.

PMID- 30100021
TI  - Identification of natural product compounds as quorum sensing inhibitors in
      Pseudomonas fluorescens P07 through virtual screening.
AB  - Pseudomonas fluorescens, a Gram-negative psychrotrophic bacteria, is the main
      microorganism causing spoilage of chilled raw milk and aquatic products. Quorum
      sensing (QS) widely exists in bacteria to monitor their population densities and
      regulate numerous physiological activities, such as the secretion of
      siderophores, swarming motility and biofilm formation. Thus, searching for quorum
      sensing inhibitors (QSIs) may be another promising way to control the
      deterioration of food caused by P. fluorescens. Here, we screened a traditional
      Chinese medicine (TCM) database to discover potential QSIs with lesser toxicity.
      The gene sequences of LuxI- and LuxR-type proteins of P. fluorescens P07 were
      obtained through whole-genome sequencing. In addition, the protein structures
      built by homology modelling were used as targets to screen for QSIs. Twenty-one
      compounds with a dock score greater than 6 were purchased and tested by biosensor
      strains (Chromobacterium violaceum CV026 and Agrobacterium tumefaciens A136). The
      results showed that 10 of the compounds were determined as hits (hit rate:
      66.67%). Benzyl alcohol, rhodinyl formate and houttuynine were effective QSIs.
      The impact of the most active compound (benzyl alcohol) on the phenotypes of P.
      fluorescens P07, including swimming and swarming motility, production of
      extracellular enzymes and siderophores, N-acylhomoserine lactone (AHLs) content
      and biofilm formation were determined. The inhibitory mechanism of benzyl alcohol
      on the QS system of P. fluorescens P07 is further discussed. This study reveals
      the feasibility of searching for novel QSIs through virtual screening.

PMID- 30100022
TI  - The Interpersonal Context of Suicide and Self-Harm in Later Life: An Invited
      Commentary on "Why Do the Very Old Self-Harm? A Qualitative Study".

PMID- 30100023
TI  - Socioeconomic deprivation is not associated with reduced survival of lung
      transplant recipients.
AB  - BACKGROUND: Important risk factors for long-term survival of lung transplant (LT)
      recipients are infection, acute graft rejection (AR) and chronic lung allograft
      dysfunction (CLAD). Socioeconomic deprivation (SED) is associated with increased
      graft failure rate after heart and kidney transplantation, but has not been
      investigated in LT recipients. The aim of this study was to evaluate an
      association between LT recipients' SED status and development of AR, CLAD, and
      long-term survival. METHODS: This was a retrospective cohort study. Over a 23 y
      period, 233 patients were identified from the Auckland City Hospital Lung
      Transplant Registry, Auckland, New Zealand. All patients were divided into two
      groups according to the 2013 New Zealand Deprivation Index Score. RESULTS: The
      incidence of AR in the higher SED group was 34.0/100 person-y (95% confidence
      interval [CI]: 24.7-46.7/100 person-y) and in the lower SED group 40.2/100 person
      y (95% CI: 33.5-48.3/100 person-y) (P = 0.373). The incidence of CLAD in the
      higher SED group was 10.7/100 person-y (95% CI: 6.2-18.4/100 person-y) and 9.3
      (6.9-12.5/100 person-y) in the lower SED group (P = 0.645). Mortality in the
      higher SED group was 12.9/100 person-y (95% CI: 9.2-17.9/100 person-y) and
      12.4/100 person-y (95% CI: 10.0-15.3/100 person-y) in the lower SED group (P =
      0.834). CONCLUSIONS: SED status of LT recipients in New Zealand has no negative
      effect on development of AR, CLAD, and patients' survival.

PMID- 30100024
TI  - Simvastatin reduces the TLR4-induced inflammatory response in human aortic valve
      interstitial cells.
AB  - BACKGROUND: Calcific aortic stenosis is a chronic inflammatory disease.
      Proinflammatory stimulation via toll-like receptor 4 (TLR4) causes the aortic
      valve interstitial cell (AVIC) to undergo phenotypic change. The AVIC first
      assumes an inflammatory phenotype characterized by the production of inflammatory
      mediators such as intercellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL
      8), and monocyte chemoattractant protein-1 (MCP-1). This change has been linked
      with an osteogenic phenotypic response. Statins have recently been shown to have
      anti-inflammatory properties. We therefore hypothesized that statins may have an
      anti-inflammatory effect on human AVICs by downregulation of TLR4-stimulated
      inflammatory responses. Our purposes were (1) to determine the effect of
      simvastatin on TLR4-induced expression of inflammatory mediators in human AVICs
      and (2) to determine the mechanism(s) through which simvastatin exert this
      effect. MATERIALS AND METHODS: Human AVICs were isolated from the explanted
      hearts of four patients undergoing cardiac transplantation. Cells were treated
      with simvastatin (50 MUM) for 1 h before stimulation with TLR4 agonist
      lipopolysaccharide (LPS, 0.2 MUg/mL). Immunoblotting (IB) was used to analyze
      cell lysates for ICAM-1 expression, and enzyme-linked immunosorbent assay was
      used to detect IL-8 and MCP-1 in cell culture media. Likewise, lysates were
      analyzed for TLR4 and nuclear factor-kappa B activation (IB). After simvastatin
      treatment, lysates were analyzed for TLR4 levels (IB). Statistics were by
      analysis of variance (P < 0.05). RESULTS: Simvastatin reduced TLR4-induced ICAM
      1, IL-8, and MCP-1 expression in AVICs. Simvastatin down-regulated TLR4 levels
      and suppressed TLR4-induced phosphorylation of nuclear factor-kappa B.
      CONCLUSIONS: These data demonstrate the potential of a medical therapy
      (simvastatin) to impact the pathogenesis of aortic stenosis.

PMID- 30100025
TI  - Pulmonary contusions in the elderly after blunt trauma: incidence and outcomes.
AB  - BACKGROUND: In the general population with blunt chest trauma, pulmonary
      contusions (PCs) are commonly identified. However, there is limited research in
      the elderly. We sought to evaluate the incidence and outcomes of PCs in elderly
      blunt trauma admissions. METHODS: We retrospectively reviewed the trauma registry
      at a level I trauma center for all blunt thoracic trauma patients aged >=65 y,
      who were admitted between 2007 and 2015. The medical records of PC patients were
      reviewed. RESULTS: There were 956 admissions with blunt thoracic trauma; of which
      778 had no pulmonary contusion (NO) and 178 had PC. The major mechanisms of
      injury were falls (58.7% NO, 39.3% PC, P <0.001) and motor vehicle crash/motor
      cycle crash (35.6% NO, 51.7% PC, P <0.001). Rib fractures were present in 79.8%
      of PC and 73.8% of NO patients, P = 0.1. PC patients more often had serious (AIS
      >=3) head/neck (30.3% versus 20.6%, P <0.001), abdomen (12.4% versus 6.6%, P
      <0.001), and extremity injuries (20.8% versus 11.4%, P <0.001). Complication
      (46.1% PC versus 26.6% NO, P <0.001) and mortality (14.0% PC versus 6.2% NO, P =
      0.0003) rates were higher in PC patients. On multivariate logistic regression
      analyses, PC presence was significantly associated with mechanical ventilation
      (odds ratio 2.5), intensive care unit admission (odds ratio 2.3), and mortality
      (odds ratio 1.9). CONCLUSIONS: Over 18.6% of elderly blunt thoracic trauma
      patients sustained PC, despite an often low energy mechanism of injury. The
      presence of a PC should prompt investigation for other serious intrathoracic and
      extrathoracic injuries. PC presence is associated with substantial morbidity and
      mortality.

PMID- 30100026
TI  - Thirty-day unplanned postoperative inpatient and emergency department visits
      following thoracotomy.
AB  - BACKGROUND: Unplanned visits to the emergency department (ED) and inpatient
      setting are expensive and associated with poor outcomes in thoracic surgery. We
      assessed 30-d postoperative ED visits and inpatient readmissions following
      thoracotomy, a high morbidity procedure. MATERIALS AND METHODS: We
      retrospectively analyzed inpatient and ED administrative data from California,
      Florida, and New York, 2010-2011. "Return to care" was defined as readmission to
      inpatient facility or ED within 30 d of discharge. Factors associated with return
      to care were analyzed via multivariable logistic regressions with a fixed effect
      for hospital variability. RESULTS: Of 30,154 thoracotomies, 6.3% were admitted to
      the ED and 10.2% to the inpatient setting within 30 d of discharge. Increased
      risk of inpatient readmission was associated with Medicare (odds ratio [OR] 1.30;
      P < 0.001) and Medicaid (OR 1.31; P < 0.0001) insurance status compared to
      private insurance and black race (OR 1.18; P = 0.02) compared to white race. Lung
      cancer diagnosis (OR 0.83; P < 0.001) and higher median income (OR 0.89; P =
      0.04) were associated with decreased risk of inpatient readmission. Postoperative
      ED visits were associated with Medicare (OR 1.24; P < 0.001) and Medicaid
      insurance status (OR 1.59; P < 0.001) compared to private insurance and Hispanic
      race (OR 1.19; P = 0.04) compared to white race. CONCLUSIONS: Following
      thoracotomy, postoperative ED visits and inpatient readmissions are common.
      Patients with public insurance were at high risk for readmission, while patients
      with underlying lung cancer diagnosis had a lower readmission risk. Emphasizing
      postoperative management in at-risk populations could improve health outcomes and
      reduce unplanned returns to care.

PMID- 30100027
TI  - Increased complications in pediatric surgery are associated with comorbidities
      and not with Down syndrome itself.
AB  - BACKGROUND: Down syndrome (DS) is a genetic condition associated with multiple
      comorbidities. While physicians may perceive that DS patients have more
      postoperative complications, the literature remains unclear. This study compared
      postoperative complications for children with and without DS who underwent
      abdominal and thoracic procedures. METHODS: The National Surgical Quality
      Improvement Program Pediatric was queried for patients aged <18 years, who
      underwent abdominal and noncardiac thoracic operations (by Current Procedural
      Terminology codes) from 2012 to 2015. The analysis compared patients based on the
      presence or absence of DS. The primary outcome was a composite of all
      postoperative complications as defined by the National Surgical Quality
      Improvement Program Pediatric. The analysis utilized chi-square, Student's t
      test, and univariate and multiple logistic regression. RESULTS: There were 91,478
      patients included, of which 1476 (1.6%) had a diagnosis of DS. Patients with DS
      had higher rates of preoperative nutritional support (38.8% versus 15.0%),
      developmental delay (61.9% versus 10.4%), and cardiac risk factors (76.5% versus
      13.8%). The overall rate of postoperative complications was 11.1%, with a greater
      proportion in DS patients (16.2% versus 10.8%, P < 0.001). On univariate
      analysis, DS was associated with increased odds of postoperative complications
      (odds ratio 1.6 95% confidence interval 1.4-1.9) compared with the non-DS group;
      however, DS was not a risk factor after adjusting for other covariates (adjusted
      odds ratio 0.86 95% confidence interval 0.7-1.1). CONCLUSIONS: A higher
      proportion of postoperative complications were observed in patients with DS.
      However, after adjusting for other risk factors, DS was not an independent risk
      factor. The increased rate of complications is likely related to the presence of
      multiple comorbidities in DS.

PMID- 30100028
TI  - Frailty score on admission predicts mortality and discharge disposition in
      elderly trauma patients over the age of 65 y.
AB  - BACKGROUND: Although many frailty scales exist, a single scale has not been
      agreed upon to define frailty. Herein, we determined whether the Canadian Study
      on Health and Aging Clinical Frailty Scale (CSHA CFS) can predict the risk of
      elderly patients for hospital mortality and discharge to skilled nursing
      facilities (SNFs) following traumatic injury. METHODS: Charts from trauma
      patients aged >=65 y admitted from December 1, 2011 to December 31, 2013 were
      retrospectively examined. Age, mechanism of injury, Glasgow coma score, systolic
      blood pressure and heart rate on arrival, injury severity score, hospital
      mortality, length of stay, and discharge disposition were recorded. Frailty
      scores were determined from admission data using the CSHA CFS. Univariate and
      multivariate analyses were performed. RESULTS: A total of 1403 patients were
      included. The mean age was 77.6 +/- 8.6 y. Patients with falls presented higher
      frailty scores than patients who sustained injuries through other mechanisms
      (4.58 +/- 1.2 versus 3.52 +/- 1.15; P < 0.00001) and were significantly older
      (79.5 +/- 8.6 versus 73.4 +/- 7.4; P <0.00001). Frailty scores of nonsurvivors
      were significantly higher than those of survivors (4.6 +/- 1.3 versus 4.2 +/-
      1.2; P <0.01). Age, Glasgow coma score, and CSHA CFS combined were associated
      with mortality (odds ratio: 1.52; confidence interval: 1.37-1.69). A higher
      frailty score was associated with earlier death and increased mortality.
      CONCLUSIONS: CSHA CFS is simple and provides frailty scores that can help
      identifying elderly patients at high risk for in-hospital mortality and discharge
      to SNF following traumatic injury.

PMID- 30100029
TI  - Improving imaging strategies in pediatric appendicitis: a quality improvement
      initiative.
AB  - BACKGROUND: Data from the American College of Surgeons National Surgical Quality
      Improvement Program identified our hospital as an outlier for preoperative
      computed tomography (CT) use in the diagnosis of acute appendicitis in children.
      We performed a quality improvement project to reduce this utilization in favor of
      ultrasound-based diagnoses (ultrasonography [US]) through creation and
      implementation of an evidence-based appendicitis algorithm. METHODS: Over a 2-y
      period (1 y preceding and 1 y following institution of the algorithm), the
      clinical information of all pediatric patients operated on for suspicion of acute
      appendicitis following imaging studies in our institution was collated. Basic
      characteristics were compared before and after protocol implementation using the
      chi-square test for categorical variables and the nonparametric, independent
      sample test of medians for numerical variables. Imaging modalities used and
      clinical outcomes were compared using chi-square analysis. RESULTS: A total of
      227 patients (117 preprotocol and 110 postprotocol implementation) were evaluated
      in our emergency department and operated on for suspicion of acute appendicitis.
      There were no differences in age, sex, race, or body mass index between the two
      periods. There were also no differences in length of stay (P = 0.27), acute and
      perforated appendicitis rates (P = 0.59), negative appendectomy rates (P = 0.40),
      or postoperative complications (P = 0.19). There was a significant reduction in
      the utilization of CT, from 65.8% to 22.0%, with a concurrent increase in the
      utilization of US (P < 0.001). CONCLUSIONS: With the implementation of a
      standardized, multidisciplinary algorithm, CT utilization was decreased and
      concurrently US utilization was increased without sacrificing diagnostic accuracy
      or patient outcomes.

PMID- 30100030
TI  - The use of mesh for inguinal hernia repair in northern Ghana.
AB  - BACKGROUND: Despite the recognition that inguinal hernia (IH) repair is cost
      effective, repair rates in low- and middle-income countries remain low. Estimated
      use of mesh in low- and middle-income countries also remains low despite
      publications about low-cost, noncommercial mesh. The purpose of our study was to
      assess the current state of IH repair in the northern and transitional zone of
      Ghana. MATERIALS AND METHODS: A retrospective review of surgical case logs of IH
      repairs from 2013 to 2017 in 41 hospitals was performed. Multivariate logistic
      regression was used to determine predictors of mesh use. RESULTS: Eight thousand
      eighty male patients underwent IH repair. The range of IH repair in each region
      was 96 to 295 (overall 123) per 100,000 population. Most cases were performed at
      district hospitals (84%) and repaired nonurgently (93%) by nonsurgeon physicians
      (66%). Suture repair was most common (85%) although mesh was used in 15%. The
      strongest predictor of mesh use was when a surgeon performed surgery (odds ratio
      [OR] 3.13, P <0.001), followed by surgery being performed in a teaching hospital
      (OR 2.31, P <0.001). Repair at a regional hospital was a negative predictor of
      mesh use (OR 0.08, P <0.001) as was the use of general anesthesia (OR 0.40, P =
      0.001). CONCLUSIONS: Most IH repairs are performed in district hospitals, by
      nonsurgeon physicians, and without mesh. Rates of repair and the use of mesh are
      higher than previous estimates in Ghana and Sub-Saharan Africa but not as high as
      high-income countries.

PMID- 30100031
TI  - Mesoappendix as potential donor site for vascularized lymph node transfer:
      anatomic study.
AB  - BACKGROUND: The standard of care for treatment of lymphedema is manual lymphatic
      drainage and compression therapy, which is time intensive and requires a life
      long commitment. Autologous lymph node transfer is a microsurgical treatment in
      which a vascularized lymph node flap is harvested with its blood supply and
      transferred to the lymphedematous region to assist with lymph fluid clearance. An
      ideal donor lymph node site minimizes the risk of iatrogenic lymphedema and other
      donor site morbidity. To address this, we have used jejunal mesentery lymph nodes
      and omental flaps and hypothesize that the mesoappendix, as a "spare part," may
      be an ideal autologous lymph node transfer donor site. METHODS: In this
      Institutional Review Board-approved study, 25 mesoappendix pathology specimens
      resected for benign disease underwent gross pathologic examination for the
      presence of lymph nodes and measurement of the appendicular artery and vein
      caliber and length. RESULTS: A single lymph node was present in two of 25
      specimens (8%). Mean arterial and vein calibers at the point of ligation were
      0.87 +/- 0.44 mm and 0.86 +/- 0.48 mm (range 0.30-2.2 mm and 0.25-2.2 mm),
      respectively. Mean arterial and vein length was 1.70 +/- 1.06 cm and 1.84 +/-
      1.09 cm (range 0.8-4.5 cm for each), respectively. CONCLUSIONS: The mesoappendix
      rarely contains a lymph node. The artery and vein calibers of 46% of the
      specimens were greater than 0.8 mm, the minimum caliber preferred for
      microsurgical anastomosis. If transplantation of a vascularized lymph node for
      the treatment of lymphedema is desired, the mesoappendix is inconsistent in
      providing adequate lymph nodes.

PMID- 30100032
TI  - Validation of American Joint Committee on Cancer eighth staging system for
      gallbladder cancer and its lymphadenectomy guidelines.
AB  - BACKGROUND: For gallbladder cancer (GBC), the American Joint Committee on Cancer
      eighth edition (AJCC 8) staging system classifies lymph node (LN) stage by the
      number of positive LN and recommends sampling of >=6 LNs. We evaluated the
      prognostic capability of the AJCC 8 for patients undergoing resection and the
      current national trends in LN staging in the context of these new recommendations
      for nodal (N) sampling. METHODS: Utilizing the National Cancer Data Base, we
      identified all gallbladder adenocarcinoma patients treated with surgical
      resection in 2004-2014. Cox regression modeling was used to calculate the
      concordance index of AJCC 8 in predicting overall survival. N sampling and
      positivity rates were analyzed over the study period. RESULTS: In our cohort,
      predicted 5-year overall survival by AJCC 8 was: stage I, 62.5%; II, 50.2%; IIIA,
      25.7%; IIIB, 22.1%; IVA, 15.7%; IVB, 6.7% (P < 0.01). The concordance index for
      the staging system was 0.832. Only 50.7% of the patients had any LN sampling to
      determine the N stage. LN sampling rates improved from 45.6% in 2004 to 55.1% in
      2013 (P < 0.001). However, only 24.5% of patients with any LN sampling had >=6
      LNs resected (12.4% of eligible cohort), with a median LN sample of two.
      CONCLUSIONS: AJCC 8 offers adequate discrimination for GBC staging, especially
      for node-positive patients. With actual GBC LN sampling rates at 50.7%, and far
      short of the >=6 LN threshold, quality improvement measures may need to focus on
      requiring any LN sampling before raising the minimum to six LNs.

PMID- 30100033
TI  - Evaluating full-thickness skin grafts in intraperitoneal onlay mesh position
      versus onlay position in mice.
AB  - BACKGROUND: Importance: Hernia surgery requires reinforcement material with few
      side effects when used in the intraperitoneal position. Autologous skin grafting
      may meet this requirement, but animal experiments are obligatory before being
      applied in humans. OBJECTIVE: To compare survival and effects of isogeneic full
      thickness skin grafts in the intraperitoneal onlay mesh (IPOM) position in mice,
      with a control group using the onlay position. Primary end point was graft
      survival and secondary end point adhesion formation and inflammation through NF
      kappaB activity. METHODS: Design: Intervention study with 8-week follow-up in
      accordance with ARRIVE criteria, performed between 2015 and 2016. SETTING: Animal
      laboratory. PARTICIPANTS: Transgenic C57BL/6 mice with isogeneic background were
      used. Recipients were female wild-type phenotype mice >3 mo (n = 24). Donors were
      male or female mice >7 mo, with phenotype-positive for the luciferase gene (n =
      20) or positive for NF-kappaB-luciferase gene (n = 4). INTERVENTION: Full
      thickness skin was grafted in the IPOM position and compared with grafts in the
      onlay position as controls. Survival was evaluated by regular longitudinal
      postoperative luminescence imaging over 8 wk. Adherence formation was evaluated
      macroscopically after sacrifice. Inflammation of full-thickness skin grafts in
      IPOM position of NF-kappaB mice was evaluated in four additional mice. Main
      outcome and measure: Survival of grafts, evaluated by luminescence. RESULTS: Ten
      animals received grafts in the IPOM position, and 10 in the onlay position as
      controls. Graft survival after 8 wk was 100% (20/20). Average luminescence at the
      end of the 8-week period was 999,597 flux (min 162,800, max 2,521,530) in the
      IPOM group (n = 10) and 769,708 flux (min 76,590, max 2,164,080) in the onlay
      control group (n = 10). No adhesions requiring sharp dissection (Jenkins' scale
      >2) were seen. Four animals with grafts in the IPOM position showed peak
      inflammation (NF-kappaB activity) 5 d after surgery subsiding toward the end of
      follow-up. CONCLUSIONS: Full-thickness skin survives as well in the IPOM position
      as in the onlay control position, and few adherences develop. Further studies are
      required to fully characterize the tissue remodeling and repair processes
      associated with IPOM skin grafting. The result is relevant in the search for
      alternative reinforcement materials to be used in complex hernia surgery in
      humans.

PMID- 30100034
TI  - alpha7 Nicotinic acetylcholine receptor contributes to the alleviation of lung
      ischemia-reperfusion injury by transient receptor potential vanilloid type 1
      stimulation.
AB  - BACKGROUND: Activation of transient receptor potential vanilloid type 1 (TRPV1)
      decreases lung ischemia-reperfusion injury (LIRI) in rabbits and rats.
      Stimulation of alpha7 nicotinic acetylcholine receptors (alpha7nAChRs) protects
      against lung injury. Here we examined whether alpha7nAChRs contribute to TRPV1
      mediated protection against LIRI. METHODS: Wild-type (WT) and TRPV1-knockout (KO)
      mice were subjected to 1-h lung ischemia by clamping left hilum, followed by 2-h
      reperfusion. WT or KO mice were pretreated with vehicle, TRPV1 agonist capsaicin,
      TRPV1 antagonist capsazepine, alpha7nAChR antagonist methyllycaconitine, or
      alpha7nAChR agonist PNU-282987. Arterial blood and lung tissues were obtained for
      blood gas, lung wet-to-dry weight ratio, interleukin (IL)1beta, IL6, tumor
      necrosis factor-alpha (TNF-alpha), apoptosis-related proteins (caspases, Bax,
      Fas), and pathologic scoring. RESULTS: Capsaicin pretreatment reduced wet-to-dry
      ratio, pathologic score, alveolar-arterial oxygen gradient (A-aDO2), and IL1beta,
      IL6, and TNFalpha levels in WT mice, with no effects in KO mice. This reduction
      was reversed by TRPV1 blockade. Furthermore, alpha7nAChR blockade before
      capsaicin exacerbated LIRI as evidenced by enhanced alveolar-arterial oxygen
      gradient, pathologic score, and IL1beta, IL6, and TNFalpha levels, while
      alpha7nAChR agonist pretreatment under TRPV1 blockade showed opposite changes.
      Capsaicin also decreased cleaved caspase-3, caspase-3/9, and Bax protein
      expression, effects abolished by TRPV1 blockade. Similarly, alpha7nAChR blockade
      diminished capsaicin-induced downregulation of apoptotic proteins, and
      alpha7nAChR activation decreased expression levels even under TRPV1 blockade.
      CONCLUSIONS: TRPV1 activation alleviates LIRI, partially dependent on alpha7nAChR
      activity. The alpha7nAChR stimulation with or without existence of TRPV1
      alleviates LIRI. Thus, alpha7nAChR is involved in the pathway of TRPV1-mediated
      protection against LIRI and the specific mechanism remains to be revealed.

PMID- 30100035
TI  - The effect of fluid resuscitation strategy on monocyte and T-cell surface
      markers.
AB  - BACKGROUND: Despite initial lifesaving benefits, posttraumatic resuscitation
      strategies have been associated with immunologic complications leading to
      systemic inflammatory response syndrome, sepsis, multiple organ failure, and late
      trauma death. Nevertheless, the direct effect on immunologic surface markers
      remains inadequately described. We hypothesized that changes in monocyte and T
      cell surface markers were associated with initial posttraumatic fluid
      resuscitation. MATERIALS AND METHODS: Data were extracted from the inflammation
      and host response to injury (Glue Grant) study. Blood samples were drawn from 492
      patients on days 0, 1, 4, 7, 14, and 28 and analyzed for 31 monocyte and T-cell
      surface markers. Resuscitation strategies during the initial 48 h were
      quantified, including transfusion of packed red blood cells (PRBCs), fresh frozen
      plasma (FFP), platelets, and crystalloids. Longitudinal surface marker
      concentration changes were quantified by the calculation of a within-patient
      signal intensity change and were associated with resuscitation strategy while
      controlling confounders. P-values were post hoc corrected using the false
      detection rate q-value. RESULTS: The monocyte surface marker (CD83) trajectory
      (as measured by a within-patient signal intensity change) was found to be
      positively associated with volume of PRBCs transfused (q = 0.002) and negatively
      associated with the transfused volume of FFP (q = 0.004). T-cell surface marker
      (CD3) was found to be negatively associated with volume of PRBCs transfused (q =
      854 * 10-9) and positively associated with the transfused volume of FFP (q =
      0.022). Platelets and crystalloid transfusion volumes were not associated with
      any surface marker trajectories. CONCLUSIONS: PRBC and FFP transfusion was
      associated with opposing effects on CD3 and CD83 trajectories, which may in part
      explain some of the protective effects of a high FFP:PRBC ratio in trauma-related
      resuscitation.

PMID- 30100036
TI  - Local excision results in comparable survival to radical resection for early
      stage rectal carcinoid.
AB  - BACKGROUND: Controversy exists regarding current National Comprehensive Cancer
      Network guidelines, which recommend local excision for rectal carcinoids <=2 cm
      and radical resection for tumors >2 cm. Given the limited data examining optimal
      surgical approach for these lesions, we queried a national database to determine
      the impact of extent of resection on survival. METHODS: Patients undergoing
      treatment for clinical stage I and II rectal carcinoid (RC) were identified from
      the National Cancer Data Base (1998-2012). The association between extent of
      surgery, tumor size, and the likelihood of pathologic lymph node positivity was
      examined. Kaplan-Meier analysis was used to compare overall survival. RESULTS: In
      total, 1900 patients were identified, of whom 1644 (86.5%) were treated with
      local excision, and 256 (13.5%) were treated with radical resection. A
      significant majority of patients with tumors <=2.0 cm (89.0%) and nearly half
      with tumors 2.1-4.0 cm (44.8%) or >4.0 cm (45.8%) underwent local excision. Nodal
      positivity was correlated with tumor size (7.1% positivity with <=2.0 cm tumors,
      31.3% with 2.1-4.0 cm tumors, and 50.0% with >4 cm tumors). However, 5-y survival
      was equivalent between surgical approaches for tumors <=2 cm (93.0% versus 93.0%)
      and tumors 2.1-4.0 cm (76.0% versus 76.0%). CONCLUSIONS: We demonstrate in early
      stage RC that nearly half of intermediate and large tumors are being treated with
      local excision outside National Comprehensive Cancer Network guidelines. In
      addition, radical resection does not appear to be associated with improved
      overall survival for tumors of any size. These findings suggest that the
      preferred approach to early-stage RCs without aggressive biological
      characteristics is local excision due to the decreased morbidity and mortality
      versus radical resection.

PMID- 30100037
TI  - Outcomes of arterial bypass preceding resection of retroperitoneal masses
      involving major vessels.
AB  - BACKGROUND: Current surgical management of retroperitoneal masses involving major
      vessels now includes complete en bloc resection with in situ venous, arterial, or
      combined reconstruction. No studies have investigated preresection arterial
      bypass for continuous lower extremity perfusion during definitive resection.
      Here, we characterize and compare the outcomes of surgery for retroperitoneal
      masses with major vascular involvement by a two-stage approach (femoral-femoral
      bypass preceding resection) and the traditional one-stage approach (consecutive
      resection and in situ vascular reconstruction). MATERIALS AND METHODS: We
      retrospectively reviewed patients who underwent resection of retroperitoneal
      masses and reconstruction of major arterial or venous structures from 2004 to
      2016. Outcomes were compared with unpaired t-tests, chi-squared tests, and Kaplan
      Meier analysis. RESULTS: Eight patients underwent a two-stage procedure, and
      seven underwent a one-stage procedure for retroperitoneal masses with vascular
      involvement. Mean (+/-SD) oncologic resection time (443 +/- 215 versus 648 +/-
      128 min, P = 0.047) and postoperative ICU stay (0.9 +/- 1.3 versus 4.4 +/- 2.9 d,
      P = 0.018) were significantly shorter for the two-stage approach. CONCLUSIONS: To
      our knowledge, this is the first report of a two-stage approach for resection of
      retroperitoneal masses with major vessel involvement. Femoral-femoral arterial
      bypass before definitive resection could be a viable option for improving
      intraoperative vascular control and decreasing perioperative complications in
      these complex procedures.

PMID- 30100038
TI  - Long-term results of cholecystectomy for biliary dyskinesia: outcomes and
      resource utilization.
AB  - BACKGROUND: The purpose of this study is to describe a cohort of pediatric
      patients undergoing cholecystectomy for biliary dyskinesia (BD) and characterize
      postoperative resource utilization. METHODS: Single-institution, retrospective
      chart review of pediatric patients after cholecystectomy for BD was done. Patient
      demographics and clinical characteristics as well as operative details and
      postoperative interventions were abstracted. Telephone follow-up was performed to
      identify persistent symptoms, characterize the patient experience, and quantify
      postoperative resource utilization. RESULTS: Forty-nine patients were included.
      Twenty-two patients (45%) were seen postoperatively by a gastroenterologist, of
      which, only 32% were known to the gastroenterologist before surgery.
      Postoperative studies included 13 abdominal ultrasounds for persistent pain, 13
      esophagogastroduodenoscopies, five endoscopic retrograde
      cholangiopancreatographies (ERCPs), one endoscopic ultrasound, one magnetic
      resonance cholangiopancreaticogram, and five colonoscopies. Of the patients with
      additional diagnostic testing postoperatively, one had mild esophagitis, three
      had sphincter of Oddi dysfunction, and one was suspected to have inflammatory
      bowel disease. Telephone survey response rate was 47%. Among respondents, 65.2%
      reported ongoing abdominal pain, nausea, or vomiting at an average of 26 mo after
      operation. Of note, all patients who underwent postoperative ERCP with
      sphincterotomy reported symptom relief following this procedure. CONCLUSIONS:
      Relief of symptoms postoperatively in pediatric patients with BD is inconsistent.
      Postoperative studies, though numerous, are of low diagnostic yield and generate
      high costs. These findings suggest that the initial diagnostic criteria and
      treatment algorithm may require revision to better predict symptom improvement
      after surgery. Improvement seen after ERCP/sphincterotomy is anecdotal but
      appears to merit further investigation.

PMID- 30100039
TI  - Noninvasive follicular thyroid neoplasm with papillary-like nuclear features
      reclassification and its impact on thyroid malignancy rate and treatment.
AB  - BACKGROUND: The reclassification of noninvasive encapsulated follicular variant
      papillary thyroid carcinoma (FVPTC) to noninvasive follicular thyroid neoplasm
      with papillary-like nuclear features (NIFTP) may have significant implications by
      changing overall malignancy rates and minimizing the extent of surgical
      treatment. METHODS: A retrospective review of 847 patients who underwent
      thyroidectomy at a single institution from January 2010 to April 2016 was
      performed. The subgroup with FVPTC (n = 181) was re-reviewed by endocrine
      pathologists for reclassification to NIFTP. The overall rate of malignancy (ROM)
      and within each Bethesda classification was determined before and after the
      reclassification of NIFTP. The extent of thyroidectomy among others in patients
      reclassified as NIFTP was further reviewed. RESULTS: Of 847 patients who
      underwent thyroidectomy, there was an overall ROM of 58% (n = 495), the majority
      being papillary thyroid cancer (PTC) (n = 454, 92%). In 181 patients with FVPTC,
      146 underwent pathology re-review. There were 32 cases (22%) reclassified as
      NIFTP, reducing the overall ROM to 55%. ROM decreased across Bethesda categories
      I to V by the following: 3% Bethesda I, 8% Bethesda II, 8% Bethesda III, 10%
      Bethesda IV, and 3% Bethesda V. Among NIFTP patients, 16 underwent total
      thyroidectomy and 16 underwent thyroid lobectomy, of which 12 had completion
      thyroidectomies (75%). Twenty patients (63%) underwent central neck dissection,
      and nine underwent postoperative radioactive iodine ablation treatment (28%).
      CONCLUSIONS: A significant proportion of patients with FVPTC reclassified as
      NIFTP may decrease the overall institutional thyroid ROM. On final pathology,
      NIFTP should be regarded as an indolent tumor requiring no further surgical
      treatment.

PMID- 30100040
TI  - Prognostic significance of red cell distribution width in esophageal squamous
      cell carcinoma.
AB  - BACKGROUND: Red cell distribution width (RDW) is routinely assessed as part of
      the complete blood count (CBC) to gather information on the heterogeneity in the
      size of circulating erythrocytes. RDW is a more sensitive screening marker for
      anemia, inflammation, and nutritional deficiencies. The purpose of this study was
      to explore the prognostic value of RDW in esophageal squamous cell carcinoma
      (ESCC) patients. METHODS: We conducted a retrospective study of data from 148
      ESCC consecutive patients who underwent potentially curative esophagectomy and
      analyzed the correlation of RDW with various clinicopathological factors.
      RESULTS: Multivariate analyses identified a high RDW (HR, 2.061; P = 0.0286) as a
      significant risk factor for cancer-specific survival (CSS). Kaplan-Meier analysis
      and the log-rank test demonstrated that patients with a high RDW had a
      significantly worse prognosis in terms of CSS than those with a low RDW (P =
      0.0011). In multivariate analysis, there was no significant relationship between
      RDW and CSS in pathological tumor node metastasis stage I or II patients.
      However, a high RDW (HR, 2.386; P = 0.0471) was confirmed to be an independent
      worse prognostic factor for CSS in pathological tumor node metastasis stage III
      cancer patients. Kaplan-Meier analysis and the log-rank test showed a significant
      relationship between RDW and CSS in patients with pathological tumor node
      metastasis stage III (P = 0.0175). CONCLUSIONS: The RDW was a significant and
      independent predictor of poor survival in ESCC patients after curative
      esophagectomy. RDW may aid clinicians in detecting signs of recurrence very early
      and effectively customize treatment regimens. RDW is thus a convenient, cost
      effective, and readily available biomarker to predict survival in ESCC.

PMID- 30100041
TI  - Variation in postacute care utilization after complex surgery.
AB  - BACKGROUND: Variation in use of postacute care (PAC), including skilled nursing
      facilities and inpatient rehabilitation, accounts for 73% of regional variation
      in Medicare spending. Studies of hospital variation in PAC use have typically
      focused on nonsurgical patients or have been limited to Medicare data.
      Consequently, there is no nationally representative data on how rates of
      postoperative discharge to PAC differ between hospitals. The purpose of this
      study was to explore hospital-level variation in PAC utilization after
      cardiovascular and abdominal surgery. MATERIALS AND METHODS: We evaluated
      3,487,365 patients from the Nationwide Inpatient Sample and 60,666 from the
      Veterans Affairs health system, who had colorectal surgery, hepatectomy,
      pancreatectomy, coronary bypass, aortic aneurysm repair, and peripheral vascular
      bypass from 2008 to 2011. For each hospital, we calculated unadjusted and risk
      adjusted observed-to-expected ratios for discharge to PAC facilities (skilled
      nursing or inpatient rehabilitation). RESULTS: A total of 631,199 (18%) non
      veterans and 4744 (8%) veterans were discharged to PAC facilities. For veterans,
      32% were >=70 y old, and 98% were men. For non-veterans, 39% were >=70, and 60%
      were men. Hospital rates of discharge to PAC facilities varied from 1% to 36% for
      veterans hospitals and from 1% to 59% for non-veteran hospitals. Risk-adjusted
      observed-to-expected ratios ranged from 0.10 to 4.15 for veterans and from 0.11
      to 4.3 for non-veteran hospitals. CONCLUSIONS: There is substantial variation in
      PAC utilization and rates of home discharge after abdominal and cardiovascular
      surgery. To reduce variation, further research is needed to understand health
      systems factors that influence PAC utilization.

PMID- 30100042
TI  - Robotic port-site hernias after general surgical procedures.
AB  - BACKGROUND: With the increasing use of the robotic platform in general surgery,
      whether 8-mm ports should be closed comes into question. We sought to
      characterize the incidence of port-site hernias (PSHs) among patients undergoing
      robotic-assisted general surgery. METHODS: A retrospective chart review of a
      single institutional database identified patients who underwent robotic-assisted
      general surgery from July 2010 to December 2016. For each patient, the number,
      type, location, and size of all ports were collected. Twelve-millimeter port
      sites were routinely closed, whereas 5-mm and 8-mm port sites were not. PSH was
      detected on review of documented physical examination and of postoperative cross
      sectional imaging, when available, in which case it was defined as a disruption
      of the fascia with or without eventration of tissue at a site of prior port
      placement. RESULTS: One hundred and seventy-eight patients underwent robotic
      assisted general surgery, with 725 total ports: 433 8-mm working ports, 72 12-mm
      working ports, 178 12-mm camera ports, and 42 5-mm assistant ports. Ninety-four
      percent of the patients were men, the mean age was 63 +/- 12, body mass index was
      29 +/- 7 kg/m2, and the median American Society of Anesthesiologists score was 3.
      Types of cases included 68 rectal (38.2%), 36 colon (20.2%), 25
      hepatopancreatobiliary (14.0%), 21 inguinal hernia (11.8%), and 28 "other"
      (15.7%) operations. At a median follow-up of 193 d, there were three PSHs through
      8-mm port sites (0.7%), two PSHs through 12-mm port sites (0.8%), and no PSH
      through 5-mm port sites. Two of the three 8-mm PSHs occurred in the early
      postoperative period and required emergent repair due to small bowel
      incarceration. CONCLUSIONS: PSHs through 8-mm robotic port sites occur
      infrequently but can cause significant morbidity. Further investigation with
      longer follow-up is warranted to better understand the true incidence of robotic
      PSH.

PMID- 30100043
TI  - The impact of aspirin use on breast cancer subtype and clinical course.
AB  - BACKGROUND: The use of aspirin has been associated with improved survival in
      patients with breast cancer, but the results have been mixed. We aim to analyze
      the impact of aspirin use before or after breast cancer diagnosis on breast
      cancer clinical characteristics and outcomes. MATERIALS AND METHODS: We performed
      a single-institution, retrospective analysis of 1113 women diagnosed with
      operable breast cancer between 1995 and 2015. Patients were grouped according to
      their aspirin use: never (944), before diagnosis (79), and after diagnosis (90).
      Clinical variables, overall survival (OS), and disease-free survival (DFS) were
      compared between groups. RESULTS: Women using aspirin before diagnosis were
      older, more likely to be black, and to have associated medical comorbidities than
      patients in other groups (all P <0.001). These patients were also more likely to
      present with hormone receptor-negative cancers, including triple-negative breast
      cancer (P = 0.002). Aspirin use before diagnosis was associated with a worse OS
      in univariate and multivariate analyses (both P <0.001), but there were no other
      differences in OS or DFS related to aspirin use. CONCLUSIONS: Despite a potential
      impact on tumor subtype in patients using aspirin before their breast cancer
      diagnosis, aspirin use does not appear to alter breast cancer-related survival.

PMID- 30100045
TI  - Premeditated versus "passionate": patterns of homicide related to intimate
      partner violence.
AB  - BACKGROUND: Intimate partner violence (IPV) is prevalent but underrecognized; at
      least 25% of United States women experience IPV within their lifetime. We
      examined the most severe consequence of IPV by exploring the patterns of death
      from IPV in a statewide database of homicide victims. MATERIALS AND METHODS: This
      is a retrospective review of the Colorado Violent Death Reporting System from
      2004 to 2015. Deaths were coded as IPV if the primary relationship between the
      suspect and victim fell into the following categories: spouse, ex-spouse,
      girlfriend/boyfriend, and ex-girlfriend/ex-boyfriend. RESULTS: We identified a
      total of 2279 homicide victims, with 295 cases of IPV homicide (12.9%). The
      majority was female victims of a male partner (n = 240, 81.4%). In nearly half of
      these (n = 108, 45%), the male suspect subsequently died by suicide as part of
      the same incident. These homicide-suicide incidents were more likely than
      homicide alone to involve a spousal relationship, more likely to involve firearms
      and less likely to involve intoxication or preceding arguments. They had a
      distinct demographic profile from other victims of IPV, mirroring suicide victims
      in terms of race and estimated income. CONCLUSIONS: These results indicate that
      there are two distinct groups of female IPV homicides, and recognizing this
      distinction may allow for the development of more effective trauma prevention
      strategies. Homicide-suicides showed a more premeditated pattern while homicide
      alone suggested a crime of passion, with a smaller proportion of firearm deaths
      and higher rates of positive toxicology findings and preceding conflict in the
      latter group.

PMID- 30100044
TI  - Impaired coronary contraction to phenylephrine after cardioplegic arrest in
      diabetic patients.
AB  - BACKGROUND: We have previously found that hyperkalemic cardioplegic arrest in the
      setting of cardiopulmonary bypass (CP/CPB) is associated with impairment of the
      coronary arteriolar response to phenylephrine in nondiabetic (ND) patients. We
      hypothesized that diabetes may alter coronary arteriolar response to alpha-1
      adrenergic agonist in the setting of CP/CPB. In this study, we further
      investigated the effects of diabetes on the altered coronary arteriolar response
      to phenylephrine in patients undergoing cardiac surgery. METHODS: Coronary
      arterioles (90-150 MUm in diameter) were harvested pre- and post-CP/CPB from the
      ND and diabetic mellitus (DM) patients (n = 8/group) undergoing cardiac surgery.
      In-vitro microvascular reactivity was examined in response to phenylephrine. The
      protein expression/localization of the alpha-1 adrenergic receptors in the atrial
      myocardium was measured by Western blotting and immunohistochemistry. RESULTS:
      Phenylephrine (10-9 to 10-4 M) induced a dose-dependent contractile response in
      both ND and DM vessels pre- and post-CP/CPB. There was no significant difference
      in the pre-CP/CPB contractile responses to phenylephrine between ND and DM
      groups. The post-CP/CPB contractile response was significantly diminished in both
      ND and DM groups compared with the respective pre-CP/CPB response (P < 0.05
      versus pre-CP/CPB). This diminished contractile response was more pronounced in
      vessels from DM patients compared with vessels from ND patients (P < 0.05 versus
      ND). There were no significant differences in the protein expression of alpha-1A
      and alpha-1B receptors in the atrial myocardium between the ND and DM groups or
      tissue harvested pre- or post-CP/CPB. CONCLUSIONS: Diabetes is associated with a
      decreased contractile response of coronary arterioles to phenylephrine in the
      setting of CP/CPB versus that observed in ND patients. This alteration may
      contribute to the vasomotor dysfunction of coronary microcirculation seen early
      after CP/CPB in patients with diabetes.

PMID- 30100046
TI  - Intestinal fatty acid-binding protein levels in patients with chronic renal
      failure.
AB  - BACKGROUND: Intestinal fatty acid-binding protein (I-FABP), a biomarker of
      enterocyte injury, has been reported to be a diagnostic marker of intestinal
      ischemia and a prognostic marker in critically ill patients. However, the
      kinetics of I-FABP in renal failure patients is unknown. We sought to identify I
      FABP levels in patients with chronic kidney disease (CKD) and end-stage kidney
      disease (ESKD) on hemodialysis (HD) and to identify the manner in which the I
      FABP levels change. MATERIALS AND METHODS: Adult patients who were admitted for
      elective cardiac surgery with either normal renal function (NRF), CKD, or ESKD on
      HD were enrolled. Serum I-FABP levels in NRF and CKD patients and in ESKD
      patients before and after HD were determined. RESULTS: A total of 124 patients
      were evaluated: 47 NRF, 53 CKD, and 24 ESKD. The I-FABP levels of the CKD
      patients and pre-HD ESKD patients were significantly higher than those of the NRF
      patients (P = 0.018 and P <0.001, respectively). I-FABP levels were significantly
      negatively correlated with the estimated glomerular filtration rate in NRF and
      CKD patients (Spearman's rho = -0.313, P = 0.002). In addition, I-FABP levels in
      ESKD patients were significantly lower after HD than those before HD (P <0.001).
      CONCLUSIONS: I-FABP levels in CKD and pre-HD ESKD patients were significantly
      higher than those in NRF patients. In addition, I-FABP was significantly
      eliminated by HD in patients with ESKD. Clinicians and researchers should
      consider this aspect of I-FABP when using it as a diagnostic and prognostic
      marker in patients with renal insufficiency.

PMID- 30100048
TI  - Comments on the analysis of scientific production in otolaryngology in Spain in
      the period 2011-2015.

PMID- 30100047
TI  - [Medical treatment of small cell lung cancer: Can we leave the area of cisplatin
      etoposide?]
AB  - Small cell lung cancer accounts for 14% of all lung cancers. It remains a major
      challenge for oncology as the progresses made in the past three decades are
      modest. After a rapid overview of current knowledge regarding somatic genomic
      alterations, this state-of-art addresses pathways to improve small-cell lung
      cancer outcome such as the targeting of DNA damage repair mechanisms firstly anti
      PARPs, inhibitory molecules of EZH2, derepression of the NOTCH pathway,
      rovalbituzumab-tesirine, inhibition of serine/threonine Aurora A kinase,
      temozolomide and its dependence on methylation of the MGMT promoter. This first
      chapter suggests the beginning of precision medicine in small cell lung cancer.
      The last section focuses on the development of immuno-oncological agents and the
      information collected from phase 1 and 2 studies: the low intensity of PD-L1
      tissue expression and the possible relationship of the activity of these agents
      as a function of tumor mutational burden are pointed out.

PMID- 30100049
TI  - Validation of the influencing factors associated with traffic violations and
      crashes on freeways of developing countries: A case study of Iran.
AB  - Among the rural roads, freeways have the maximum allowable speed limit. This
      subject increases the tendency of drivers to use these kinds of roads, and
      despite its positive effects, it has caused numerous problems. One of them is the
      increase in the rate of traffic violations and crashes. The amount of crashes per
      kilometer in Iran's freeways is almost twice the other rural roads. Hence,
      finding a solution to this problem is of particular importance. This research
      intends to validate some of the influencing factors which cause traffic
      violations and crashes in freeways and determine their amount of influence
      through statistical models. For this purpose, the authors considered violations
      and crashes for 36 road segments as dependent variables and other factors as
      independent ones. Since dependent variables were count, discrete, and non-zero,
      the proposed models were Poisson and Zero-truncated Poisson. The processing of
      the models indicated that the amounts of Akaike Information Criterion (AIC) and
      Bayesian Information Criterion (BIC) indices for the Zero-truncated Poisson model
      are less than those of the Poisson model and the result of the Pseudo-R2 test for
      this model is within the acceptable range. Moreover, the result of Chi-square
      test which shows the proximity of expected and observed amounts was better for
      Zero-truncated Poisson model. Thus, this model has a considerable advantage
      against Poisson model. Final models indicated that the average speed has a
      positive correlation with the number of violations and crashes and as it
      increases, they increase too. Besides, peripheral landscapes, number of
      interchanges, number of passing lanes, and exemption from paying toll have an
      opposite relationship with violations and crashes.

PMID- 30100050
TI  - Polytrauma independent of therapeutic intervention alters the gastrointestinal
      microbiome.
AB  - BACKGROUND: This study characterizes the gastrointestinal (GI) microbiome in a
      pre-clinical polytrauma hemorrhage model. METHODS: Rats (n = 6) were
      anesthetized, hemorrhaged 20% of their blood volume, and subjected to a femur
      fracture and crush injuries to the small intestine, liver, and limb skeletal
      muscle without resuscitation. Fecal samples were collected pre-injury and 2 h
      post-injury. Purified DNA from the samples underwent 16s rRNA sequencing for
      microbial quantification. Bacterial diversity analysis and taxonomic
      classification were performed. RESULTS: Following injury, the gut microbial
      composition was altered with a shift in beta diversity and significant
      differences in the relative abundance of taxa. The relative abundance of the
      families Lachnospiraceae and Mogibacteriaceae was increased at 2 h, while
      Barnesiellaceae and Bacteroidaceae were decreased. Alpha diversity was unchanged.
      CONCLUSIONS: The GI microbiome is altered in rats subjected to a polytrauma
      hemorrhage model at 2 h post-injury in the absence of antibiotics or therapeutic
      interventions.

PMID- 30100051
TI  - Palliative care and hospital readmissions in patients with advanced heart
      failure: Insights from the PAL-HF trial.

PMID- 30100052
TI  - Management of cardiogenic shock in acute decompensated chronic heart failure: The
      ALTSHOCK phase II clinical trial.
AB  - Management of acute decompensated heart failure patients presenting with
      cardiogenic shock (CS) is not straightforward, as few data are available from
      clinical trials. Stabilization before left ventricle assist device (LVAD) or
      heart transplantation (HTx) is strongly advocated, as patients undergoing LVAD
      implant or HTx in critical status have worse outcomes. This was a multicenter
      phase II study with a Simon 2-stage design, including 24 consecutive patients
      treated with low-moderate epinephrine doses, whose refractory CS prompted
      implantation of intra-aortic balloon pump (IABP) which was subsequently upgraded
      with peripheral venoarterial extracorporeal membrane oxygenation. At admission,
      patients had severe left ventricular dysfunction and overt CS, 7 patients could
      be managed only with inotropic therapy, and 16 patients were transitioned to IABP
      and 1 to IABP and venoarterial extracorporeal membrane oxygenation; the median
      duration of epinephrine therapy was 7 days (interquartile range 6-15), and the
      median dose was 0.08 MUg/kg/min (interquartile range 0.05-0.1); 21 patients
      (87.5%) survived at 60 days (primary outcome); among them, 13 (61.9%) underwent
      LVAD implantation, 2 (9.5%) underwent HTx, and 6 (28.6%) improved on medical
      treatment, indicating that early and intensive treatment of CS in chronic
      advanced heart failure patients with low-dose epinephrine and timely short-term
      mechanical circulatory support leads to satisfactory outcomes.

PMID- 30100054
TI  - Principles of DNA methylation and their implications for biology and medicine.
AB  - DNA methylation represents an annotation system for marking the genetic text,
      thus providing instruction as to how and when to read the information and control
      transcription. Unlike sequence information, which is inherited, methylation
      patterns are established in a programmed process that continues throughout
      development, thus setting up stable gene expression profiles. This DNA
      methylation paradigm is a key player in medicine. Some changes in methylation
      closely correlate with age providing a marker for biological ageing, and these
      same sites could also play a part in cancer. The genome continues to undergo
      programmed variation in methylation after birth in response to environmental
      inputs, serving as a memory device that could affect ageing and predisposition to
      various metabolic, autoimmune, and neurological diseases. Taking advantage of
      tissue-specific differences, methylation can be used to detect cell death and
      thereby monitor many common diseases with a simple cell-free circulating-DNA
      blood test.

PMID- 30100053
TI  - Enhanced Recovery After Surgery (ERAS) in gynecologic oncology: System-wide
      implementation and audit leads to improved value and patient outcomes.
AB  - OBJECTIVE: Enhanced recovery pathways have been shown to reduce length of stay
      without increasing readmission or complications in numerous areas of surgery.
      Uptake of gynecologic oncology ERAS guidelines has been limited. We describe the
      effect of ERAS guideline implementation in gynecologic oncology on length of
      stay, patient outcomes, and economic impact for a province-wide single-payer
      system. METHODS: We compared pre- and post-guideline implementation outcomes in
      consecutive staging and debulking patients at two centers that provide the
      majority of surgical gynecologic oncology care in Alberta, Canada between March
      2016 and April 2017. Clinical outcomes and compliance were obtained using the
      ERAS Interactive Audit System. Patients were followed until 30 days after
      discharge. Negative binomial regression was employed to adjust for patient
      characteristics. RESULTS: We assessed 152 pre-ERAS and 367 post-ERAS
      implementation patients. Mean compliance with ERAS care elements increased from
      56% to 77.0% after implementation (p < 0.0001). Median length of stay for all
      surgeries decreased from 4.0 days to 3.0 days post-ERAS (p < 0.0001), which
      translated to an adjusted LOS decrease of 31.4% (95% CI = [21.7% - 39.9%], p <
      0.0001). In medium/high complexity surgery median LOS was reduced by 2.0 days (p
      = 0.0005). Complications prior to discharge decreased from 53.3% to 36.2% post
      ERAS (p = 0.0003). There was no significant difference in readmission (p =
      0.6159), complications up to 30 days (p = 0.6274), or mortality (p = 0.3618)
      between the cohorts. The net cost savings per patient was $956 (95%CI: $162 to
      $1636). CONCLUSIONS: Systematic implementation of ERAS gynecologic oncology
      guidelines across a healthcare system improves patient outcomes and saves
      resources.

PMID- 30100056
TI  - Expression of phosphatase and tensin homolog and programmed cell death ligand 1
      in adenosquamous carcinoma of the lung.
AB  - BACKGROUND: Lung adenosquamous carcinoma (ASC) is a rare variant of non-small
      cell lung cancer (NSCLC) with poor prognosis. Certain biological differences may
      exist between these tumors and other common histological types of NSCLC,
      including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). The
      phosphoinositide 3-kinase (PI3K) pathway, which links oncogenes and multiple
      receptor classes to essential cellular functions, is activated by phosphatase and
      tensin homolog (PTEN) loss. The PTEN loss has been suggested to induce programmed
      cell death ligand 1 (PD-L1) expression in various cancer types. OBJECTIVE: Here,
      we sought to determine the relationships between the expression of PTEN and PD-L1
      in each component of ASC with ADC and SCC, and clinical parameters. MATERIAL AND
      METHODS: Tissue microarrays of 148 cases of surgically resected lung ADC and 102
      cases of SCC, as well as full sections from 28 ASC cases, were analyzed
      immunohistochemically for the expression of PTEN and PD-L1. RESULTS: PD-L1
      expression was similar between the adenocarcinoma component of ASC vs. lung ADC
      and between the squamous component of ASC vs. lung SCC. PTEN loss was higher in
      lung ADC than in the adenocarcinoma component of ASC and significantly higher in
      lung SCC than in the squamous component of ASC. PD-L1 expression was higher in
      the squamous component than in the glandular component of the 28 ASC cases, but
      PTEN loss was similar. Overall, PTEN loss was higher in lung SCC than in lung ADC
      and both components of ASC. In lung SCC and glandular portions of ASC, PD-L1
      expression levels were significantly associated with those of PTEN. The loss of
      PTEN correlated with smoking status in patients with lung ADC. CONCLUSIONS: Our
      results implied that both squamous and glandular components of ASC may share the
      same oncogenic driver pathway for carcinogenesis. However, the squamous cell
      components of ASC likely escape the immune surveillance better than the glandular
      components due to higher PD-L1 expression.

PMID- 30100055
TI  - The heterozygous R155C VCP mutation: Toxic in humans! Harmless in mice?
AB  - Heterozygous missense mutations in the human VCP gene cause inclusion body
      myopathy associated with Paget disease of bone and fronto-temporal dementia
      (IBMPFD) and amyotrophic lateral sclerosis (ALS). The exact molecular mechanisms
      by which VCP mutations cause disease manifestation in different tissues are
      incompletely understood. In the present study, we report the comprehensive
      analysis of a newly generated R155C VCP knock-in mouse model, which expresses the
      ortholog of the second most frequently occurring human pathogenic VCP mutation.
      Heterozygous R155C VCP knock-in mice showed decreased plasma lactate, serum
      albumin and total protein concentrations, platelet numbers, and liver to body
      weight ratios, and increased oxygen consumption and CD8+/Ly6C + T-cell fractions,
      but none of the typical human IBMPFD or ALS pathologies. Breeding of heterozygous
      mice did not yield in the generation of homozygous R155C VCP knock-in animals.
      Immunoblotting showed identical total VCP protein levels in human IBMPFD and
      murine R155C VCP knock-in tissues as compared to wild-type controls. However,
      while in human IBMPFD skeletal muscle tissue 70% of the total VCP mRNA was
      derived from the mutant allele, in R155C VCP knock-in mice only 5% and 7% mutant
      mRNA were detected in skeletal muscle and brain tissue, respectively. The lack of
      any obvious IBMPFD or ALS pathology could thus be a consequence of the very low
      expression of mutant VCP. We conclude that the increased and decreased fractions
      of the R155C mutant VCP mRNA in man and mice, respectively, are due to missense
      mutation-induced, divergent alterations in the biological half-life of the human
      and murine mutant mRNAs. Furthermore, our work suggests that therapy approaches
      lowering the expression of the mutant VCP mRNA below a critical threshold may
      ameliorate the intrinsic disease pathology.

PMID- 30100057
TI  - Green synthesis and characterization of silver nanoparticles using Enicostemma
      axillare (Lam.) leaf extract.
AB  - In the present article, the facile green synthesis of silver nanoparticles
      (AgNPs) using aqueous leaf extract of Enicostemma axillare (Lam.) has reported.
      This is a simple, cost-effective, stable for a long time and reproducible aqueous
      synthesis method to obtain a self-assembly Ag nanoparticles. The size and shape
      of Ag nanoparticles were characterized by XRD, TEM, and SEM-EDS. The formation
      and stability of the reduced silver nanoparticles in the colloidal solution were
      monitored by UV-Vis spectrophotometer analysis. Zeta potential was confirmed by
      DLS study. The mean particle diameter of silver nanoparticles was calculated from
      the TEM, SEM and the size of the particles was measured between 15 and 20 nm. TEM
      analysis revealed the spherical shape of the particles. Crystalline nature of the
      nanoparticles in the face-centred cubic structure are confirmed by the peaks in
      the XRD pattern corresponding to (111), (200), (220) and (311) planes. This study
      showed the biogenic, environmentally friendly and cost-effective synthesis and
      characterization of the silver nanoparticles.

PMID- 30100058
TI  - GALNT3 inhibits NF-kappaB signaling during influenza A virus infection.
AB  - Protein glycosylation, attaching glycans covalently onto amino acid side chains
      of protein by various glycosyltransferase, is the most common post-translational
      modification. The UDP-GalNAc transferase 3 (GANLT3), encoded by Galnt3, transfers
      N-acetyl-d-galactosamine to hydroxyl groups of the side chains of Ser/Thr
      residues, initiating mucin type O-glycosylation of proteins. Most researches as
      yet focus on the involvement and abnormal expression of GALNT3 in various tumors.
      In this study, we found that GALNT3 was significantly decreased in the lungs
      after influenza A virus (IAV) infection in mice. Overexpression of GALNT3 in cell
      lines markedly inhibited IAV replication. Further experiments demonstrated that
      GALNT3 inhibited NF-kappaB signaling by preventing the translocation of
      phosphorylated P65 into nucleus. Therefore, our results reveal an important role
      of GALNT3 in regulating host responses during IAV infection, indicating the broad
      functions of the GALNT family, and the direct involvement of GALNTs during viral
      infections.

PMID- 30100059
TI  - PAS-histidine kinases PHK1 and PHK2 exert oxygen-dependent dual and opposite
      effects on gametophore formation in the moss Physcomitrella patens.
AB  - Two-component systems, versatile signaling mechanisms based on phosphate transfer
      between component proteins, must have played important roles in adaptation and
      diversification processes in land plant evolution. We previously demonstrated
      that two Per-Arnt-Sim (PAS)-histidine kinases, PHK1 and PHK2, repress gametophore
      formation in the moss Physcomitrella patens under aerobic conditions, and that,
      in eukaryotes, the presence of their homologs is restricted to early-diverging
      streptophyte linages. We assessed here whether or not PHKs play a role in oxygen
      signaling. When submerged under water, the double disruption line for PHK1 and
      PHK2 formed fewer gametophores than the wild-type line (WT) both under light-dark
      cycles or continuous light, indicating that PHKs promote gametophore formation
      under an aquatic environment, in contrast to aerobic conditions. Similarly, in an
      artificial low-oxygen condition, the double disruption line formed fewer
      gametophores than WT. These results indicate that PHKs exert dual and opposite
      effects on gametophore formation depending on oxygen status. This study adds
      important insight into functional versatility and evolutionary significance of
      two-component systems in land plants.

PMID- 30100060
TI  - Bufalin inhibits cell proliferation and migration of hepatocellular carcinoma
      cells via APOBEC3F induced intestinal immune network for IgA production signaling
      pathway.
AB  - OBJECTIVE: This study aimed to evaluate functions of APOBEC3F gene in biological
      process of hepatocellular carcinoma (HCC) and anti-tumor mechanisms of bufalin.
      METHODS: Effect of APOBEC3F and bufalin on cell proliferation and migration
      abilities were evaluated by CCK-8, wounding healing tests and transwell assays in
      SK-Hep1 and Bel-7404 cells. Bioinformatic analysis were also used to compare
      APOBEC3F expression levels, detect coexpressed genes and enrichment of pathways.
      RESULTS: APOBEC3F was overexpressed in tumor tissues compared to adjacent tissues
      in HCC patients. And, APOBEC3F promotes cell proliferation and migration in SK
      Hep1 and Bel-7404 cells. Bufalin inhibits cell proliferation and migration and
      reduces APOBEC3F expression. GO and KEGG enrichment of APOBEC3F-coexpressed genes
      revealed that APOBEC3F might active intestinal immune network for IgA production
      signaling pathway, leading to malignant biological behaviors of HCC cells.
      Additionally, siAPOBEC3F could decrease pIgR, CCR9, CCR10 and CXCR4 protein
      levels. And, bufalin inhibits the pIgR, CCR9, CCR10 and CXCR4 protein
      expressions. CONCLUSIONS: Bufalin inhibits cell proliferation and migration of
      HCC cells via APOBEC3F induced intestinal immune network for IgA production
      signaling pathway.

PMID- 30100061
TI  - Loss of circadian protein TIMELESS accelerates the progression of cellular
      senescence.
AB  - TIMELESS protein is known to be essential for normal circadian rhythms. Aging is
      a deleterious process which affects all the physiological functions of complex
      organisms including the circadian rhythms. The circadian aging may produce
      disorganization among the circadian rhythms, arrhythmicity and even,
      disconnection from the environment, resulting in a detrimental situation to the
      organism. However, the role of circadian genes on the aging process is poorly
      understood. In present study, we found TIMELESS was down-regulated in cellular
      senescence, and further research indicated E2F1 bound to the promotor of TIMELESS
      and regulated its expression in cellular senescence. Knockdown of TIMELESS
      accelerated cellular senescence induced by ectopic expression of RasV12, and
      overexpression of TIMELESS delayed this kind onset of senescence. Meanwhile,
      micrococcal nuclease assays proved depletion of TIMELESS exacerbated genomic
      instability at the onset of senescence. Together, our data reveal that TIMELESS
      plays a role in OIS, which is associated with genome stability changing.

PMID- 30100062
TI  - Probing labeling-induced lysosome alterations in living cells by imaging-derived
      mean squared displacement analysis.
AB  - Lysosomes are not merely degradative organelles but play a central role in
      nutrient sensing, metabolism and cell-growth regulation. Our ability to study
      their function in living cells strictly relies on the use of lysosome-specific
      fluorescent probes tailored to optical microscopy applications. Still, no report
      thus far quantitatively analyzed the effect of labeling strategies/procedures on
      lysosome properties in live cells. We tackle this issue by a recently developed
      spatiotemporal fluctuation spectroscopy strategy that extracts structural (size)
      and dynamic (diffusion) properties directly from imaging, with no a-priori
      knowledge of the system. We highlight hitherto neglected alterations of lysosome
      properties upon labeling. In particular, we demonstrate that Lipofectamine
      reagents, used to transiently express lysosome markers fused to fluorescent
      proteins (FPs) (e.g. LAMP1-FP or CD63-FP), irreversibly alter the organelle
      structural identity, inducing a ~2-fold increase of lysosome average size. The
      organelle structural identity is preserved, instead, if electroporation or
      Effectene are used as transfection strategies, provided that the expression
      levels of the recombinant protein marker are kept low. This latter condition can
      be achieved also by generating cell lines stably expressing the desired FP-tagged
      marker. Reported results call into question the interpretation of a massive
      amount of data collected so far using fluorescent protein markers and suggest
      useful guidelines for future studies.

PMID- 30100063
TI  - Cisplatin sensitivity in breast cancer cells is associated with particular DMTF1
      splice variant expression.
AB  - The cyclin D binding myb-like transcription factor 1 (DMTF1) is a tumor
      suppressor gene that activates p14ARF transcription and thereby stabilizing the
      p53 tumor suppressor. The DMTF1 gene locus encodes for three different
      alternatively spliced isoforms, namely DMTF1alpha, beta and gamma. The oncogenic
      DMTF1beta isoform negatively interferes with the transcriptional activity of
      DMTF1alpha. Increased DMTF1beta is associated with increased cell proliferation
      in a variety of cancer cell types. In this study, we aimed at identifying the
      role of DMTF1 isoforms in response to cisplatin treatment in breast cancer cells.
      First, we used SKBR3 (cisplatin sensitive) and MCF7 (cisplatin resistant) breast
      cancer cell lines to quantify DMTF1 expression in response to cisplatin
      treatment. Total DMTF1 mRNA levels increased in a dose dependent manner in both
      cell lines upon cisplatin treatment. However, the mRNA levels of the isoforms
      revealed that the sensitive cell line, SKBR3, showed increased levels of both
      isoforms, whereas the resistant cell, MCF7, only showed increased levels of the
      oncogenic DMTF1beta isoform. Silencing all DMTF1 isoforms led to increased cell
      survival upon cisplatin treatment. Furthermore, we found a significant increase
      in the percentage of quiescent cells in SKBR3 shDMTF1. Together, our data suggest
      that DMTF1 expression levels are associated with increased cisplatin resistance.

PMID- 30100064
TI  - Down-regulation of miR-193a-3p promotes osteoblast differentiation through up
      regulation of LGR4/ATF4 signaling.
AB  - Emerging evidence indicates that microRNAs (miRNAs) are crucial regulators of
      osteoblast differentiation. A previous study has reported that miR-193a-3p
      expression is altered during the induction of osteoblast differentiation.
      However, the precise biological function and regulatory mechanism of miR-193a-3p
      during osteoblast differentiation remains unclear. In this study, we aimed to
      investigate the precise role and underlying mechanism of miR-193a-3p in
      regulating osteoblast differentiation. The results showed that miR-193a-3p
      expression was significantly down-regulated during the induction of osteoblast
      differentiation. Functional experiments demonstrated that the overexpression of
      miR-193a-3p impeded osteoblast differentiation while miR-193a-3p inhibition
      promoted osteoblast differentiation. Bioinformatics analysis and a luciferase
      assay revealed that leucine-rich repeat-containing G-protein coupled receptor 4
      (LGR4), a critical regulator of osteoblast differentiation, was a target gene of
      miR-193a-3p. We showed that miR-193a-3p negatively regulated the expression of
      LGR4 and activating transcription factor 4 (ATF4). Moreover, the knockdown of
      LGR4 or ATF4 significantly reversed the promotion effect of miR-193a-3p
      inhibition on osteoblast differentiation. Overall, these findings demonstrate
      that miR-193a-3p regulates osteoblast differentiation by modulating LGR4/ATF4
      signaling and suggests that the miR-193a-3p/LGR4/ATF4 regulation axis may play an
      important role in regulating bone remodeling.

PMID- 30100065
TI  - miR-7-5p acts as a tumor suppressor in bladder cancer by regulating the hedgehog
      pathway factor Gli3.
AB  - Although important progresses have been made in the diagnosis and treatment of
      bladder cancer (BCa), the overall survival for patients with advanced BCa remains
      poor. It is necessary to uncover the molecular mechanism underlying the
      initiation and progression of bladder cancer. According to previous reports,
      mircoRNAs (miRNAs) can regulate tumorigenesis by targeting their downstream
      mRNAs. This study aims to explore and analyze a novel miRNA-mRNA axis which can
      regulate the progression of bladder cancer. Based on the microarray analysis, 182
      mRNAs were found to be upregulated in BCa tissues. Gene oncology (GO) analysis
      and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that these
      upregulated mRNAs are related with hedgehog pathway. Gli3, an important factor of
      hedgehog pathway, belongs to these 182 upregulated mRNAs. Therefore, Gli3 was
      chosen to do further study. Kaplan-Meier analysis revealed that highly expressed
      Gli3 predicted unfavorable prognosis for patients with BCa. Results of functional
      experiments indicated the inhibitory effects of silenced Gli3 on cell
      proliferation, migration and EMT progress. Mechanically, Gli3 was the target mRNA
      of miR-7-5p in BCa cells. Finally, rescue assays were performed to validate the
      specific function of miR-7-5p/Gli3 axis in BCa progression. According to all
      data, we concluded that miR-7-5p acts as a tumor suppressor in BCa by
      downregulating Gli3.

PMID- 30100066
TI  - Optineurin E50K triggers BDNF deficiency-mediated mitochondrial dysfunction in
      retinal photoreceptor cell line.
AB  - Optineurin (OPTN) mutations are linked to glaucoma pathology and E50K mutation
      shows massive cell death in photoreceptor cells and retinal ganglion cells.
      However, little is known about E50K-mediated mitochondrial dysfunction in
      photoreceptor cell degeneration. We here show that overexpression of E50K
      expression triggered BDNF deficiency, leading to Bax activation in RGC-5 cells.
      BDNF deficiency induced mitochondrial dysfunction by decreasing mitochondrial
      maximal respiration and reducing intracellular ATP level in RGC-5 cells. However,
      BDNF deficiency did not alter mitochondrial dynamics. Also, BDNF deficiency
      resulted in LC3-mediated mitophagosome formation in RGC-5 cells. These results
      strongly suggest that E50K-mediated BDNF deficiency plays a critical role in
      compromised mitochondrial function in glaucomatous photoreceptor cell
      degeneration.

PMID- 30100067
TI  - Dual effect of hemin on renal ischemia-reperfusion injury.
AB  - Acute kidney injury (AKI) is a major public health concern, which is contributing
      to serious hospital complications, chronic kidney disease (CKD) and even death.
      Renal ischemia-reperfusion injury (IRI) remains a leading cause of AKI. The
      stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against
      renal IRI and may be preventively induced using hemin prior to renal insult. This
      HO-1 induction pathway called hemin preconditioning is largely known to be
      effective. Therefore, HO-1 might be an interesting therapeutic target in case of
      predictable AKI (e.g. partial nephrectomy or renal transplantation). However, the
      use of hemin to mitigate established AKI remains poorly characterized. Mice
      underwent bilateral renal IRI for 26 min or sham surgery. After surgical
      procedure, animals were injected either with hemin (5 mg/kg) or vehicle. Twenty
      four hours later, mice were sacrificed. Despite strong HO-1 induction, hemin
      treated mice exhibited significant renal damage and oxidative stress as compared
      to vehicle-treated mice. Interestingly, higher dose of hemin is associated with
      more severe IRI-induced AKI in a dose-dependent relation. To determine whether
      hemin preconditioning remains efficient to dampen postoperative hemin-amplified
      IRI-induced AKI, we pretreated mice either with hemin (5 mg/kg) or vehicle 24 h
      prior to surgical procedure. Then, all mice (hemin- and vehicle-pretreated)
      received postoperative injection of hemin (5 mg/kg) to amplify IRI-induced AKI.
      In comparison to vehicle, prior administration of hemin to renal IRI mitigated
      hemin-amplified IRI-induced AKI as attested by fewer renal damage, inflammation
      and oxidative stress. In conclusion, hemin may have a dual effect on renal IRI,
      protective or deleterious, depending on the timing of its administration.

PMID- 30100068
TI  - Caspase-1 regulates cellular trafficking via cleavage of the Rab7 adaptor protein
      RILP.
AB  - Intracellular trafficking is a tightly regulated cellular process, mediated in
      part by Rab GTPases and their corresponding effector proteins. Viruses have
      evolved mechanisms to hijack these processes to promote their lifecycles. Here we
      describe a mechanism by which cleavage of the Rab7 adaptor protein, RILP (Rab
      interacting lysosomal protein) is induced by viral infection. We report that RILP
      is directly cleaved by caspase-1 and we have identified a novel caspase-1
      recognition site at aspartic acid 75 within the RILP sequence. Alanine
      substitution at D75 blocks caspase-1-mediated RILP cleavage. Full-length RILP
      localizes in a tight vesicular structure near the perinuclear region while the
      cleaved form of RILP re-distributes throughout the cytoplasm. However, cleavage
      alone was insufficient to re-localize RILP to the cellular periphery and re
      localization required specific phosphorylation events near the caspase-1
      recognition site. The combination of cleavage and phosphorylation were both
      needed for release from the dynein component p150Glued and redistribution of
      CD63+ve intracellular vesicles.

PMID- 30100069
TI  - Propranolol increases vascular permeability through pericyte apoptosis and
      exacerbates oxygen-induced retinopathy.
AB  - Retinopathy of prematurity (ROP) is an eye disease that causes blindness due to
      delayed vascular growth, retinal ischemia, and resulting abnormal angiogenesis.
      Nonselective beta-antagonist propranolol is in clinical trials for the treatment
      of ROP due to its effect of reducing VEGF expression and inhibiting retinal
      angiogenesis in oxygen-induced ROP models (OIR), but the mechanism by which
      propranolol acts on ROP vessels is still unclear. In the present study, we have
      focused on the effect of propranolol on pericyte survival and vascular
      permeability. We demonstrated that propranolol increases pericyte apoptosis more
      sensitively than endothelial cells (ECs), thereby weakening EC tight junctions to
      increase endothelial permeability in co-cultures of pericytes and ECs.
      Mechanistically, pericyte apoptosis by propranolol was due to the inhibition of
      Akt signaling pathway. We also demonstrated that propranolol increases pericyte
      loss and vascular permeability of retinal vessels in a mouse model of OIR. These
      results suggest that propranolol may be negative for blood vessels in retinas of
      OIR, and that the efficacy of propranolol for the treatment of ROP needs to be
      more thoroughly verified.

PMID- 30100070
TI  - Colostral transmission of BTV-8 antibodies from dairy cows six years after
      vaccination.
AB  - Bluetongue virus (BTV) antibodies were analysed in 27 Swiss calves born in 2016
      at the age of 16-19 days using competitive enzyme-linked-immunosorbent-assay
      (cELISA) and virus neutralization test (VNT) (animal trial permission number:
      75684). Obligatory documentation proved that 15 of 27 dams were BTV-8 vaccinated
      once or three times in 2008-2010. The offsprings of the non-vaccinated dams were
      seronegative. Two of three calves and 11 of 12 calves descending from dams who
      had been vaccinated one or three times, respectively, had BTV specific serum
      antibodies. As Switzerland is considered BTV-free from 2010 to 2016, it is likely
      that BTV-8 antibodies were transferred via colostrum. Furthermore, we confirmed
      neutralizing cross-reactivity of BTV-8 with BTV-4 antibodies as 5 samples
      positive for BTV-8 were also reactive with BTV-4 antibodies.

PMID- 30100071
TI  - Autoimmune diseases after hepatitis B immunization in adults: Literature review
      and meta-analysis, with reference to 'autoimmune/autoinflammatory syndrome
      induced by adjuvants' (ASIA).
AB  - BACKGROUND: To assess if hepatitis B vaccination in adults is causally associated
      with autoimmune diseases. Such causation has been claimed based mainly on case
      reports and uncontrolled studies, and a syndrome 'Autoimmune/autoinflammatory
      Disorder Induced by Adjuvants' (ASIA) has been claimed to be linked to
      immunization, particularly hepatitis B vaccination. METHODS: Review of peer
      reviewed literature from January 1990 to March 2017 identifying controlled
      studies with documented incidence of autoimmune diseases occurring after
      hepatitis B vaccinations in adults. From 1297 studies identified, 259 were
      further assessed and 49 reviewed further; 19 relevant papers reporting 21 results
      are reviewed here, and 14 results included in a meta-analysis. RESULTS: Overall
      no association between hepatitis B vaccination and the onset of autoimmune
      diseases was seen. The overall odds ratio was 1.06, with 95% confidence limits of
      0.93-1.21, with non-significant heterogeneity. Only one study showed a
      significant excess risk between hepatitis B immunisation and autoimmune disease.
      CONCLUSIONS: Despite multiple case reports, there is no reliable scientific
      evidence of autoimmune diseases being caused by hepatitis B vaccinations.

PMID- 30100072
TI  - Overview of Breast Cancer Screening and Diagnosis.
AB  - Screening mammography saves lives. The mainstay of screening has been
      mammography. Multiple alternative options, however, for supplemental imaging are
      now available. Some are just improved anatomic delineation whereas others include
      physiology added to anatomy. A third group (molecular imaging) is purely
      physiologic. This article describes and compares the available options and for
      which patient populations they should be used.

PMID- 30100073
TI  - Molecular Classification of Breast Cancer.
AB  - Breast cancer is a heterogeneous disease, observed traditionally by morphology
      and protein expression but, more recently with the advent of modern molecular
      technologies, at the genomic and transcriptomic level. This review describes the
      association between the different molecular subtypes with the histologic subtypes
      of breast cancer alongside some of their major genomic characteristics and
      illustrates how these subtypes may affect the appearance of tumors on imaging
      studies. The authors aim to show how molecular stratification can be used to
      augment traditional methods to improve our understanding of breast cancers and
      their clinical management.

PMID- 30100075
TI  - Diagnostic Role of Fluorodeoxyglucose PET in Breast Cancer: A History to Current
      Application.
AB  - Histologic subtype, receptor status, and other biologic factors greatly affect
      the avidity of breast malignancy on fluorodeoxyglucose (FDG) PET. FDG
      PET/computed tomography (CT) has demonstrated excellent value in the evaluation
      of extra-axillary nodal and distant metastases. Patients with early-stage breast
      cancers do not benefit from FDG PET/CT; however, unsuspected distant metastases
      may be revealed by systemic staging of locally advanced breast cancers by FDG
      PET/CT, and this has substantial impact on patient management. FDG PET/CT has
      demonstrated value in the evaluation of treatment response and in detection of
      disease recurrence.

PMID- 30100077
TI  - Nuclear Medicine Imaging Techniques for Detection of Skeletal Metastases in
      Breast Cancer.
AB  - Bone is the most common site of metastases from advanced breast cancer. Whole
      body bone scintigraphy has been most frequently used in the process of managing
      cancer patients; its advantage is that it provides rapid whole-body imaging for
      screening of osteoblastic or sclerotic/mixed bone metastases at reasonable cost.
      Recent advanced techniques, such as single-photon emission computed tomography
      (SPECT)/CT, quantitative analysis, and bone scan index, contribute to better
      understanding of the disease state. More recent advances in machines and PET
      drugs improve the staging of the skeleton with higher sensitivity and
      specificity.

PMID- 30100074
TI  - Overview of Breast Cancer Therapy.
AB  - Breast cancer treatment is multidisciplinary. Most women with early stage breast
      cancer are candidates for breast-conserving surgery with radiotherapy or
      mastectomy. The risk of local recurrence and the chance of survival does not
      differ with these approaches. Sentinel node biopsy is used for axillary staging,
      and individualized approaches are minimizing the need for axillary dissection in
      women with positive sentinel nodes. Adjuvant systemic therapy is used in most
      women based on proven survival benefit, and molecular profiling to individualize
      treatment based on risk is now a clinical reality for patients with hormone
      receptor-positive cancers.

PMID- 30100078
TI  - Role of Fludeoxyglucose in Breast Cancer: Treatment Response.
AB  - After an overview of the principles of fludeoxyglucose-PET/computed tomography
      (CT) in breast cancer, its advantages and limits to evaluate treatment response
      are discussed. The metabolic information is helpful for early assessment of the
      response to neoadjuvant chemotherapy and could be used to monitor treatment,
      especially in aggressive breast cancer subtypes. PET/CT is also a powerful method
      for early assessment of the treatment response in the metastatic setting. It
      allows evaluation of different sites of metastases in a single examination and
      detection of a heterogeneous response. However, to use PET/CT to assess
      responses, methodology for image acquisition and analysis needs standardization.

PMID- 30100076
TI  - Dedicated Breast Gamma Camera Imaging and Breast PET: Current Status and Future
      Directions.
AB  - Recent advances in nuclear medicine instrumentation have led to the emergence of
      improved molecular imaging techniques to image breast cancer: dedicated gamma
      cameras using gamma-emitting 99mTc-sestamibi and breast-specific PET cameras
      using 18F-fluorodeoxyglucose. This article focuses on the current role of such
      approaches in the clinical setting including diagnosis, assessing local extent of
      disease, monitoring response to therapy, and, for gamma camera imaging, possible
      supplemental screening in women with dense breasts. Barriers to clinical adoption
      and technologies and radiotracers under development are also discussed.

PMID- 30100079
TI  - Clinical Potential of Estrogen and Progesterone Receptor Imaging.
AB  - Molecular imaging using 16alpha-[18F]fluoro-17beta-estradiol (FES) and 18F-fluoro
      furanyl-norprogesterone PET can assess in vivo function of steroid hormone
      receptors in breast cancer. These experimental agents have been tested in many
      single-center clinical trials and show promise to elucidate prognosis and predict
      endocrine therapy response. The current multicenter trial of FES-PET imaging will
      help bring this radiotracer closer to clinical use. There is tremendous potential
      for these tracers to advance drug development, enhance understanding of estrogen
      receptor-positive tumor biology, and personalize treatment.

PMID- 30100080
TI  - Clinical Potential of Human Epidermal Growth Factor Receptor 2 and Human
      Epidermal Growth Factor Receptor 3 Imaging in Breast Cancer.
AB  - Increased expression of the human epidermal growth factor receptor (HER) protein
      family are targets in breast cancer for imaging and therapy. Imaging modalities
      targeting HER2 and HER3 can diagnose breast cancer with a specific, biologically
      relevant target. Repeat biopsies do not address heterogeneity intratumorally or
      between primary disease and metastasis. HER2- and HER3-targeted PET is an
      important tool to diagnose disease in breast cancer and evaluate response to
      targeted therapies. PET and single photon emission computed tomography with
      radiolabeled biomolecules can be used to detect and quantify specific targets,
      conferring a better understanding of the behavior and effectiveness of
      treatments.

PMID- 30100081
TI  - Amino Acid Metabolism as a Target for Breast Cancer Imaging.
AB  - Amino acids are an alternate energy source to glucose, and amino acid metabolism
      is up-regulated in multiple malignancies, including breast cancers. Multiple
      amino acid radiotracers have been used to image breast cancer with unique
      strengths and weaknesses. 11C-methionine uptake correlates with S-phase fraction
      in breast cancer and may be useful for evaluation of treatment response. Invasive
      lobular breast cancers may demonstrate greater 18F-fluciclovine avidity than 18F
      fluorodeoxyglucose. Thus, different histologic subtypes of breast cancer may use
      diverse metabolic pathways and may be better imaged by different tracers.

PMID- 30100083
TI  - Uses and Opportunities for Molecular Imaging in Patients with Breast Cancer.

PMID- 30100082
TI  - Imaging Tumor Proliferation in Breast Cancer: Current Update on Predictive
      Imaging Biomarkers.
AB  - Uncontrolled growth is a hallmark of cancer; imaging cell proliferation can
      provides an early indicator of therapeutic response. This capability is
      especially well-matched to the emerging cell cycle-specific chemotherapeutics
      with the goal of identifying patients that benefit from these treatments early in
      the course of treatment to guide personalized therapy. This article focuses on
      investigational cell proliferation imaging PET radiotracers to evaluate tumor
      proliferation in the setting of cell cycle-targeted chemotherapy and endocrine
      therapy for metastatic breast cancer.

PMID- 30100085
TI  - A One-Penny Imputed Genome from Next-Generation Reference Panels.
AB  - Genotype imputation is commonly performed in genome-wide association studies
      because it greatly increases the number of markers that can be tested for
      association with a trait. In general, one should perform genotype imputation
      using the largest reference panel that is available because the number of
      accurately imputed variants increases with reference panel size. However, one
      impediment to using larger reference panels is the increased computational cost
      of imputation. We present a new genotype imputation method, Beagle 5.0, which
      greatly reduces the computational cost of imputation from large reference panels.
      We compare Beagle 5.0 with Beagle 4.1, Impute4, Minimac3, and Minimac4 using 1000
      Genomes Project data, Haplotype Reference Consortium data, and simulated data for
      10k, 100k, 1M, and 10M reference samples. All methods produce nearly identical
      accuracy, but Beagle 5.0 has the lowest computation time and the best scaling of
      computation time with increasing reference panel size. For 10k, 100k, 1M, and 10M
      reference samples and 1,000 phased target samples, Beagle 5.0's computation time
      is 3* (10k), 12* (100k), 43* (1M), and 533* (10M) faster than the fastest
      alternative method. Cost data from the Amazon Elastic Compute Cloud show that
      Beagle 5.0 can perform genome-wide imputation from 10M reference samples into
      1,000 phased target samples at a cost of less than one US cent per sample.

PMID- 30100084
TI  - Biallelic Mutations in ADPRHL2, Encoding ADP-Ribosylhydrolase 3, Lead to a
      Degenerative Pediatric Stress-Induced Epileptic Ataxia Syndrome.
AB  - ADP-ribosylation, the addition of poly-ADP ribose (PAR) onto proteins, is a
      response signal to cellular challenges, such as excitotoxicity or oxidative
      stress. This process is catalyzed by a group of enzymes referred to as poly(ADP
      ribose) polymerases (PARPs). Because the accumulation of proteins with this
      modification results in cell death, its negative regulation restores cellular
      homeostasis: a process mediated by poly-ADP ribose glycohydrolases (PARGs) and
      ADP-ribosylhydrolase proteins (ARHs). Using linkage analysis and exome or genome
      sequencing, we identified recessive inactivating mutations in ADPRHL2 in six
      families. Affected individuals exhibited a pediatric-onset neurodegenerative
      disorder with progressive brain atrophy, developmental regression, and seizures
      in association with periods of stress, such as infections. Loss of the Drosophila
      paralog Parg showed lethality in response to oxidative challenge that was rescued
      by human ADPRHL2, suggesting functional conservation. Pharmacological inhibition
      of PARP also rescued the phenotype, suggesting the possibility of postnatal
      treatment for this genetic condition.

PMID- 30100086
TI  - A Model for Genome-First Care: Returning Secondary Genomic Findings to
      Participants and Their Healthcare Providers in a Large Research Cohort.
AB  - There is growing interest in communicating clinically relevant DNA sequence
      findings to research participants who join projects with a primary research goal
      other than the clinical return of such results. Since Geisinger's MyCode
      Community Health Initiative (MyCode) was launched in 2007, more than 200,000
      participants have been broadly consented for discovery research. In 2013 the
      MyCode consent was amended to include a secondary analysis of research genomic
      sequences that allows for delivery of clinical results. Since May 2015,
      pathogenic and likely pathogenic variants from a set list of genes associated
      with monogenic conditions have prompted "genome-first" clinical encounters. The
      encounters are described as genome-first because they are identified independent
      of any clinical parameters. This article (1) details our process for generating
      clinical results from research data, delivering results to participants and
      providers, facilitating condition-specific clinical evaluations, and promoting
      cascade testing of relatives, and (2) summarizes early results and participant
      uptake. We report on 542 participants who had results uploaded to the electronic
      health record as of February 1, 2018 and 291 unique clinical providers notified
      with one or more participant results. Of these 542 participants, 515 (95.0%) were
      reached to disclose their results and 27 (5.0%) were lost to follow-up. We
      describe an exportable model for delivery of clinical care through secondary use
      of research data. In addition, subject and provider participation data from the
      initial phase of these efforts can inform other institutions planning similar
      programs.

PMID- 30100088
TI  - Sedations: Safety, competency, efficiency.

PMID- 30100087
TI  - Characterization of a Human-Specific Tandem Repeat Associated with Bipolar
      Disorder and Schizophrenia.
AB  - Bipolar disorder (BD) and schizophrenia (SCZ) are highly heritable diseases that
      affect more than 3% of individuals worldwide. Genome-wide association studies
      have strongly and repeatedly linked risk for both of these neuropsychiatric
      diseases to a 100 kb interval in the third intron of the human calcium channel
      gene CACNA1C. However, the causative mutation is not yet known. We have
      identified a human-specific tandem repeat in this region that is composed of 30
      bp units, often repeated hundreds of times. This large tandem repeat is unstable
      using standard polymerase chain reaction and bacterial cloning techniques, which
      may have resulted in its incorrect size in the human reference genome. The large
      30-mer repeat region is polymorphic in both size and sequence in human
      populations. Particular sequence variants of the 30-mer are associated with risk
      status at several flanking single-nucleotide polymorphisms in the third intron of
      CACNA1C that have previously been linked to BD and SCZ. The tandem repeat arrays
      function as enhancers that increase reporter gene expression in a human neural
      progenitor cell line. Different human arrays vary in the magnitude of enhancer
      activity, and the 30-mer arrays associated with increased psychiatric disease
      risk status have decreased enhancer activity. Changes in the structure and
      sequence of these arrays likely contribute to changes in CACNA1C function during
      human evolution and may modulate neuropsychiatric disease risk in modern human
      populations.

PMID- 30100089
TI  - Meta-analysis of the effects of normal saline on mortality in intensive care.
AB  - INTRODUCTION AND OBJECTIVE: To evaluate, by means of a meta-analysis, the effect
      of normal saline on mortality in intensive care patients, when compared with the
      use of balanced crystalloids. MATERIAL AND METHOD: Published controlled clinical
      trials, randomised and sequential prospective studies in time, evaluating the
      mortality when physiological saline was used in patients admitted to intensive
      care units. Electronic search was performed in Medline, Embase, Cochrane Library,
      ISI Proceedings, and Web of Science, as well as a manual search of selected
      references. An independent evaluation was performed by 2 investigators.
      Discrepancies were resolved by consensus in the working group. Contingency tables
      were performed, and the OR with confidence intervals of each study were obtained.
      Heterogeneity was assessed by I2. Publication bias was assessed using funnel plot
      and Egger test. RESULTS: A total of 8 articles were selected for the meta
      analysis of mortality, which included a total of 20,684 patients. A significant
      association was observed between the use of saline and mortality in intensive
      care patients (OR 1.0972; 95% CI 1.0049-1.1979), when compared to the use of
      balanced crystalloids. No statistical evidence of publication bias (Egger,
      P=.5349) was found. In the sensitivity analysis, none of the studies
      substantially modified the overall outcome if it was eliminated from the meta
      analysis. CONCLUSIONS: There may be an increase in mortality associated with the
      use of saline in patients admitted to intensive care when comparing with the use
      of balanced crystalloids.

PMID- 30100091
TI  - Up-regulation of TNF Receptor-associated Factor 7 after spinal cord injury in
      rats may have implication for neuronal apoptosis.
AB  - TNF receptor-associated factor 7 (TRAF7), is an E3 ubiquitin ligase for several
      proteins involved in the activation of TLR-dependent NF-kappaB signaling. TRAF7
      links TNF receptor family proteins to signaling pathways, thus participates in
      regulating cell death and survival mediated by TNF family ligands. To date, the
      biological function of TRAF7 after spinal cord injury (SCI) is still with limited
      acquaintance. In this study, we have performed an acute SCI model in adult rats
      and investigated the dynamic changes of TRAF7 expression in the spinal cord. Our
      results showed that TRAF7 was up-regulated significantly after SCI, which was
      paralleled with the levels of the apoptotic protein active caspase-3.
      Immunofluorescent labeling showed that TRAF7 was co-localizated with active
      caspase-3 in neurons. To further investigate the function of TRAF7, an apoptosis
      model was established in primary neuronal cells. When TRAF7 was knocked down by
      specific short interfering RNA (siRNA), the protein levels of active caspase-3
      and the number of apoptotic primary neurons were significantly decreased in our
      study. Taken together, our findings suggest that the change of TRAF7 protein
      expression plays a key role in neuronal apoptosis after SCI.

PMID- 30100090
TI  - Research Participation of a Professional Organization in Clinical Trials: The
      Association of Black cardiologists Clinical Trial Investigator Identification
      Project.
AB  - INTRODUCTION: Black individuals continue to be underrepresented in clinical
      trials despite efforts by the National Institutes of Health and the Federal Drug
      Administration to increase their enrollment. Health care providers play a
      critical role in the recruitment of patients into clinical trials, as they have
      established relationships and are uniquely positioned to make referrals for
      participation. While prior initiatives have focused on training black physicians
      to conduct clinical research, we sought to determine the potential of utilizing a
      professional organization as a resource to identify established investigators to
      champion recruitment of underrepresented racial and ethnic populations. The
      Association of Black Cardiologists (ABC) is a non-profit organization with a
      mission to eliminate racial and ethnic disparities in cardiovascular disease and
      may provide a conduit for recruiting investigators. The purpose of this study was
      to examine the feasibility of using the ABC membership to identify investigators
      with an established track record in clinical trials. METHODS/RESULTS: Utilizing a
      roster of ABC members, we searched Scopus to quantify ABC member publications
      from 1999 to 2015 and identify members who have been active in clinical trials.
      Within the membership of 2037 individuals, we identified 794 with peer-reviewed
      publications, and 109 who co-authored manuscripts involving randomized clinical
      trials. The manuscripts largely focused on hypertension and heart failure,
      conditions that have a disproportionately greater affect on black individuals.
      CONCLUSION: Members of the ABC have varied amounts of research productivity. We
      identified a group of experienced investigators to engage in efforts aimed at
      recruiting/enrolling underrepresented racial and ethnic populations in clinical
      trials of cardiovascular disease.

PMID- 30100092
TI  - HER2: An emerging target in colorectal cancer.
AB  - Despite advances in the treatment of metastatic colorectal cancer (CRC) the 5
      year survival of patients with this disease remains low. A small proportion of
      CRCs overexpress the HER2 oncogene and the effective targeting of this pathway in
      other malignancies such as breast and gastric cancer has led to efforts to
      determine if it can also be exploited as a target in CRC. Activation of the HER2
      pathway as a bypass signalling pathway has been identified as a mechanism of
      resistance for antiepidermal growth factor receptor antibody therapy in both the
      first line and salvage settings. It has also been shown that RAS and BRAF wild
      type metastatic CRC enriches for the presence of HER2 amplification. This
      knowledge, in addition to preclinical data providing a rationale for dual anti
      HER2 targeted therapy has led to several clinical trials. To date, recently
      published and presented early phase data provide promising evidence suggesting
      anti-HER2 therapy may have a potentially beneficial role in the treatment of HER2
      positive metastatic CRC. Namely, the HERACLES-A and MyPathway studies have shown
      benefit in a small number of patients with the use of combination trastuzumab
      lapatinib and trastuzumab-pertuzumab, respectively. However, data from larger
      clinical trials are required before HER2-directed therapy is incorporated into
      standard treatment paradigms for CRC. This review presents an overview of
      epidermal growth factor receptor and HER2 pathways in CRC and discusses
      preclinical and clinical studies carried out in this field to date. There is
      potential that with continued evolution of data in this area, HER2 may become a
      validated therapeutic target and thus, anti-HER2 therapy may become an additional
      treatment option for a small population of patients with metastatic CRC.

PMID- 30100093
TI  - Reply.

PMID- 30100094
TI  - Interaction with touchscreen smartphones in patients with essential tremor and
      healthy individuals.
AB  - INTRODUCTION: Smartphones use in biomedical research is becoming more prevalent
      in different clinical settings. We performed a pilot study to obtain information
      on smartphone use by patients with essential tremor (ET) and healthy controls,
      with a view to determining whether performance of touchscreen tasks is different
      between these groups and describing touchscreen interaction factors. METHOD: A
      total of 31 patients with ET and 40 sex- and age-matched healthy controls
      completed a descriptive questionnaire about the use of smartphones. Participants
      subsequently interacted with an under-development Android application, and
      performed 4 tests evaluating typical touchscreen interaction gestures; each test
      was performed 5 times. RESULT: The type of smartphone use and touchscreen
      interaction were not significantly different between patients and controls. Age
      and frequency of smartphone use are key factors in touchscreen interaction.
      CONCLUSION: Our results support the use of smartphone touchscreens for research
      into ET, although further studies are required.

PMID- 30100095
TI  - Acute Postobstructive Pulmonary Edema Following Laryngospasm in Elderly Patients:
      A Case Report.
AB  - Only a few cases regarding postobstructive pulmonary edema following laryngospasm
      in older patients aged more than 60 years have been reported; however, acute
      pulmonary edema or pulmonary hemorrhage would be more deadly to elderly patients
      who have cerebrovascular disease than young healthy adults. After review of the
      literature, we report an unusual case of a 67-year-old man with ischemic
      cerebrovascular disease, who underwent carotid angioplasty and stenting and
      experienced severe pulmonary edema and hemorrhage secondary to laryngospasm after
      general anesthesia with laryngeal mask airway. The patient required positive
      pressure ventilation, supportive treatment, and active cerebroprotection in the
      intensive care setting for 3 days before the edema resolved, and subsequently
      made a complete recovery without new onset of neurologic sequelae. The possible
      pathophysiological mechanisms, precaution, and preventative strategy of
      postobstructive pulmonary edema in older patients are discussed.

PMID- 30100096
TI  - Variables Describing Individuals With Improved Pain and Function With a Primary
      Complaint of Low Back Pain: A Secondary Analysis.
AB  - OBJECTIVES: The purpose of this study was to identify descriptive factors in
      individuals with a primary complaint of low back pain (LBP) associated with
      improved pain and function after receiving physical therapy for LBP with or
      without manual therapy and exercise directed at the femoroacetabular joints.
      METHODS: Participants were enrolled in a randomized clinical trial investigating
      physical therapy interventions for their LBP, with or without interventions
      directed at the femoroacetabular joints (hips). A participant was deemed
      recovered if all of the following were met: Numeric Pain Rating Scale (NPRS)
      score of <=2 points, <=10% on the modified Oswestry Disability Index at
      discharge, and a global rating of change score of +4 at both 2 weeks and
      discharge. Logistic regression modelling determined descriptor variables that
      best predicted treatment recovery. RESULTS: Data from 90 participants were
      included in the analysis, with 44% (n = 40) achieving recovery by discharge from
      physical therapy (average 7.95 [+/-4.68]) visits. The variables of concurrent hip
      problems, lower body mass index <=25.4, an irritable condition, and a baseline
      NPRS score of 4 points or less were retained in the final model (R2 = .384).
      Having a concurrent hip problem had the highest odds of achieving recovery in the
      model (odds ratio: 5.34, 95 % confidence interval: 1.31-21.8). CONCLUSIONS: The
      findings for the patients in this study suggest that those with a concurrent hip
      problem, a lower body mass index, irritable symptoms, and a baseline NPRS score
      of 4 points or less were associated with greater odds of achieving recovery with
      multimodal physical therapy interventions. Further research should continue to
      investigate the interplay between the lumbar spine and hip joints.

PMID- 30100097
TI  - Does exposure of pregnant women to epidemic respiratory syncytial virus affect
      the severity of bronchiolitis?
AB  - INTRODUCTION: Passive transplacental immunity against respiratory syncytial virus
      (RSV) appears to mediate in the protection of the infant for the first 6 months
      of life. Lower environmental exposure in pregnant women to RSV epidemic may
      influence the susceptibility of these infants to infection by lowering the levels
      of antibodies that are transferred to the fetus. OBJECTIVES: To contrast the risk
      of severe disease progression in infants with acute bronchiolitis by RSV,
      according to the mother's level of exposure to epidemic. METHOD: Retrospective
      cohort study of previously healthy infants with RSV-acute bronchiolitis during 5
      epidemics was made. We compared the severity of the infection in those born
      during the period of risk (when is less likely the mother's exposure to epidemic
      and the transfer of antibodies to the fetus: October 15th-December 15th in our
      latitude) with the rest of acute bronchiolitis. Bivariate analysis was performed
      regarding birth in period of risk and the rest of variables, using the Chi-square
      test. Multivariate logistic regression analysis was performed to study possible
      classical confounding factors. RESULTS: 695 infants were included in the study.
      356 infants were born during the period of risk. Of the 56 patients requiring
      admission to PICU, 40 of them (71.4%) were born in this period (p=0.002). In the
      multivariate analysis, the birth in the period of risk showed a 6.5 OR (95% CI:
      2.13-19.7) independently of the rest of variables. CONCLUSIONS: The worst
      clinical disease progression of the acute bronchiolitis by the RSV in less than 6
      months age is related to lower exposure of the pregnant woman to the RSV
      epidemic.

PMID- 30100098
TI  - Risk factors for antimicrobial-resistant Neisseria gonorrhoeae and
      characteristics of patients infected with gonorrhea.

PMID- 30100099
TI  - Conventional Ultrasound, Immunohistochemical Factors and BRAFV600E Mutation in
      Predicting Central Cervical Lymph Node Metastasis of Papillary Thyroid Carcinoma.
AB  - The study was aimed at evaluating the correlation between central cervical lymph
      node metastasis (CLNM) in papillary thyroid carcinoma (PTC) patients and
      ultrasound (US) features, immunohistochemical factors and BRAFV600E mutation. A
      total of 225 consecutive patients (225 PTCs) who had undergone surgery were
      included. All PTCs were pre-operatively analysed by US with respect to size,
      components, echogenicity, shape, margins, microcalcification, multiple cancers or
      not, internal vascularity and capsule contact or involvement. The presence of
      four immunohistochemical factors, including cytokeratin 19, human bone marrow
      endothelial cell 1, galectin-3 and thyroid peroxidase, and BRAFV600E mutation was
      also evaluated. Univariate and multivariate analyses were performed to identify
      the risk factors for central CLNM, and a risk model was established.
      Pathologically, 44% (99/225) of the PTCs had central CLNMs. Multivariate analysis
      revealed that size <=10mm, microcalcification, internal vascularity, capsule
      contact or involvement and BRAFV600E mutation were independent risk factors for
      central CLNM. The risk score for central CLNM was calculated as follows: risk
      score = 1.5 * (if lesion size <=10 mm) + 1.9 * (if microcalcification) + 0.8 *
      (if internal flow) + 3.0 * (if capsule contact or involvement) + 1.5 * (if
      BRAFV600E mutation). The rating result was divided into six stages, and the
      relevant risk rates of central CLNM were 0% (0/1), 0% (0/22), 7.4% (4/54), 48.6%
      (34/70), 71.2% (42/59) and 100% (19/19), respectively. In conclusion, PTC <=10mm,
      microcalcification, internal vascularity, capsule contact or involvement and
      BRAFV600E mutation are risk factors for central CLNM. The risk model may be
      useful in treatment planning and management of patients with PTCs.

PMID- 30100100
TI  - ?

PMID- 30100101
TI  - Re: "Changes in lipid metabolism in pediatric patients with severe sepsis and
      septic shock".

PMID- 30100102
TI  - Mutations of deubiquitinase OTUD1 are associated with autoimmune disorders.
AB  - Dysregulation of innate immunity accompanied by excessive interferon production
      contributes to autoimmune disease. However, the mechanism by which the immune
      response is modulated in autoimmune disorders is largely unknown. Here we
      identified loss-of-function mutations of OTUD1 associated with multiple
      autoimmune diseases. Under inflammatory conditions, inducible OTUD1 acts as an
      immune checkpoint and blocks RIG-I-like receptors signaling. As a deubiquitinase,
      OTUD1 directly interacts with transcription factor IRF3 and removes the K63
      linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuclear
      translocation and transcriptional activity. In contrast, OTUD1 mutants impair its
      suppressive effects on IRF3 via attenuating the OTUD1 deubiquinase activity or
      its association with IRF3. Moreover, we found FOXO3 signaling is required for
      OTUD1 induction upon antigenic stimulation. Our data demonstrate that OTUD1 is
      involved in maintaining immune homeostasis and loss-of-function mutations of
      OTUD1 enhance the immune response and are associated with autoimmunity.

PMID- 30100103
TI  - Evaluation of hybrid anion exchanger containing cupric oxide for As(III) removal
      from water.
AB  - The aim of this study was investigate of arsenite adsorption on a hybrid polymer
      based on a polystyrene/divinylbenzene macroporous anion exchanger containing
      cupric oxide deposited within its porous structure. The study included batch
      kinetic and equilibrium experiments, and investigation of influence of the pH,
      regeneration of spent adsorbent and the column process on arsenic(III)
      adsorption. The experimental data were evaluated using kinetic, isotherm and
      fixed-bed column models. The adsorption capacity calculated from the Langmuir
      model was 6.61 mg As(III) g-1. The adsorption rate was controlled by both
      chemisorption of arsenic on the adsorbent surface and external diffusion, and at
      a higher initial As(III) concentration also by intraparticle diffusion. The spent
      adsorbent was easily regenerated with 1.0 M NaOH solution. Based on batch
      adsorption studies and X-ray photoelectron spectroscopic analyses a mechanism of
      As(III) adsorption was proposed. Arsenite removal proceeded in two stages:
      oxidation to arsenate on the CuO surface, followed by an ion exchange reaction.
      The studied hybrid polymer also showed very good adsorption characteristics under
      the dynamic regime. The S-shape of breakthrough curves and insignificant
      influence of bed height, initial concentration and flow rate on the adsorption
      capacity confirmed its applicability in water treatment.

PMID- 30100104
TI  - Final Effectiveness and Safety Results of NABUCCO: Real-World Data From a
      Noninterventional, Prospective, Multicenter Study in 697 Patients With Metastatic
      Breast Cancer Treated With nab-Paclitaxel.
AB  - BACKGROUND: One of the most effective chemotherapies for metastatic breast cancer
      (MBC) is nab-paclitaxel (nab-P), which is approved for treatment of MBC after
      failure of first-line therapy and when anthracyclines are not indicated.
      Randomized clinical trials have shown high efficacy and acceptable toxicity. Real
      world data of nab-P in MBC, however, are still limited. PATIENTS AND METHODS: The
      prospective multicenter noninterventional study NABUCCO collected data on the
      routine treatment of patients with MBC receiving nab-P in 128 sites across
      Germany. The primary objective was time to progression. Secondary objectives were
      overall response rate, overall survival, safety, and quality of life. RESULTS:
      Between April 2012 and April 2015, a total of 705 patients with MBC at 128 active
      sites had been enrolled. A total of 697 patients had evaluable data with a median
      follow-up of 17.7 months. Median time to progression was 5.9 months (95%
      confidence interval, 5.6-6.4), overall response rate was 37.2%, and median
      overall survival was 15.6 months (95% confidence interval, 14.2-17.2). The
      results were similar in patients aged < 65 versus >= 65 years as well as in
      patients who received nab-P on a weekly or a triweekly schedule. The most
      frequently reported grade 3/4 adverse events were leukopenia (55, 7.9%),
      peripheral sensory neuropathy (30, 4.3%), and infections (29, 4.2%). Patients
      reported no apparent treatment-related impact on global quality of life.
      CONCLUSION: The results of the NABUCCO study confirm the clinical trial outcomes
      and the favorable safety profile of nab-P in patients with metastatic breast
      cancer in a real-world setting.

PMID- 30100106
TI  - Preserved anabolic threshold and capacity as estimated by a novel stable tracer
      approach suggests no anabolic resistance or increased requirements in weight
      stable COPD patients.
AB  - BACKGROUND & AIMS: Assessing the ability to respond anabolic to dietary protein
      intake during illness provides important insight in the capacity of lean body
      mass maintenance. We applied a newly developed stable tracer approach to assess
      in one session in patients with chronic obstructive pulmonary disease (COPD) and
      healthy older adults both the minimal amount of protein intake to obtain protein
      anabolism (anabolic threshold) and the efficiency of dietary protein to promote
      protein anabolism (anabolic capacity). METHODS: We studied 12 clinically and
      weight stable patients with moderate to very severe COPD (mean +/- SE forced
      expiratory volume in 1 s: 36 +/- 3% of predicted) and 10 healthy age-matched
      older adults. At 2-h intervals and in consecutive order, all participants
      consumed a mixture of 0.0, 0.04, 0.10 and 0.30 g hydrolyzed casein protein*kg ffm
      1*2 h-1 and carbohydrates (2:1). We assessed whole body protein synthesis (PS),
      breakdown (PB), net PS (PS-PB) and net protein balance (phenylalanine (PHE)
      intake - PHE to tyrosine (TYR) hydroxylation) by IV primed and continuous
      infusion of L-[ring-2H5]PHE and L-[13C9,15N]-TYR. Anabolic threshold (net protein
      balance = 0) and capacity (slope) were determined on an individual basis from the
      assumed linear relationship between protein intake and net protein balance.
      RESULTS: We confirmed a linear relationship between protein intake and net
      protein balance for all participants (R2 range: 0.9988-1.0, p <= 0.0006). On
      average, the anabolic threshold and anabolic capacity were comparable between the
      groups (anabolic threshold COPD vs. healthy: 3.82 +/- 0.31 vs. 4.20 +/- 0.36
      MUmol PHE * kg ffm-1 * hr-1; anabolic capacity COPD vs. healthy: 0.952 +/- 0.007
      and 0.954 +/- 0.004). At protein intake around the anabolic threshold (0.04 and
      0.10 g protein*kg ffm-1*2 h-1), the increase in net PS resulted mainly from PB
      reduction (p < 0.0001) whereas at a higher protein intake (0.30 g protein*kg ffm
      1*2 h-1) PS was also stimulated (p < 0.0001). CONCLUSIONS: The preserved anabolic
      threshold and capacity in clinically and weight stable COPD patients suggests no
      disease related anabolic resistance and/or increased protein requirements. TRIAL
      REGISTRY: ClinicalTrials.gov; No. NCT01734473; URL: www.clinicaltrials.gov.

PMID- 30100105
TI  - ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Vitamins.

PMID- 30100108
TI  - No gender differences in growth patterns in a cohort of children with cystic
      fibrosis born between 1986 and 1995.
AB  - BACKGROUND & AIMS: A higher mortality rate at young ages has been reported in
      cystic fibrosis (CF) girls compared to boys. The reasons of this gap remain
      unclear but may be related to a different evolution of the disease, in terms of
      growth and lung function throughout childhood and adolescence. This study aimed
      at investigating gender differences in growth patterns in a cohort of children
      with CF through a longitudinal study, and as secondary objectives, to evaluate
      gender differences in forced expiratory volume in one second (FEV1) trend and
      transplant-free survival. METHODS: We performed an historical cohort study of 203
      CF patients born between 1986 and 1995. Weight and height were recorded from the
      time of CF diagnosis to the age of 18 years. Generalized estimated equations were
      used to evaluate the effect of gender on changes in z-score of BMI-for-age and z
      score of height-for-age and FEV1. Transplant-free survival to age 18 was computed
      by the Kaplan-Meier estimator. RESULTS: Girls did not show a worse growth pattern
      as compared to boys. The odds of being underweight [Odds Ratio (OR) for girls:
      0.85, 95% CI: 0.51; 1.39] or stunted [OR for girls: 0.79, 95% CI: 0.42; 1.49]
      were not significantly different between genders. FEV1 trend was also similar in
      boys and girls, as well as the probability of surviving to age 18 without
      receiving lung transplantation (boys: 0.88, 95% CI: 0.82-0.95, girls: 0.92, 0.87
      0.98, P = 0.26). CONCLUSIONS: In a cohort of children with CF born between 1986
      and 1995, no gender differences in growth patterns were observed. This finding
      suggests that CF girls and boys have benefited equally from the advances in
      treatments that have occurred over the last three decades.

PMID- 30100109
TI  - The association between treatment beliefs and engagement in care in first episode
      psychosis.

PMID- 30100107
TI  - ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Amino
      acids.

PMID- 30100110
TI  - Enhancement of microalga Haematococcus pluvialis growth and astaxanthin
      production by electrical treatment.
AB  - In this study, we investigated the effects of electrical treatment on
      Haematococcus pluvialis growth. The slow growth of H. pluvialis is a major
      limitation for its mass production. We discovered that electrical treatment may
      promote the growth of H. pluvialis. To evaluate optimal growth-promoting
      conditions, the algal growth rate was investigated at various voltages. The
      optimum current was identified as 100 mA (voltage: 25 V). In comparison with the
      non-treated cells, those subjected to electrical treatment showed a 1.2 fold
      increase in cell density. Further experiments confirmed the direct impact of
      electrical treatment on the growth of H. pluvialis. The periodic application of
      electrical voltage resulted in a significant increase in the dry weight and
      astaxanthin production. The astaxanthin content in the periodic application of
      electrical treatment was 32.6 mg/L, which was a 10% increase compared to those in
      the non-treated controls. This strategy may serve as a novel approach to enhance
      H. pluvialis growth as well as astaxanthin production.

PMID- 30100111
TI  - Robotic versus open partial nephrectomy for highly complex renal masses:
      Comparison of perioperative, functional, and oncological outcomes.
AB  - INTRODUCTION: We aimed to compare perioperative, functional and oncological
      outcomes between robot-assisted partial nephrectomy (RAPN) and open partial
      nephrectomy (OPN) for highly complex renal tumors (R.E.N.A.L. nephrometry Score >
      9). METHODS: A retrospective review of 1,497 patients who consecutively underwent
      partial nephrectomy at a single academic tertiary center between 2008 and 2016
      was performed to get data about patients who underwent RAPN and OPN for renal
      masses with RENAL score > 9. Baseline, perioperative, functional, and oncological
      outcomes were compared. RESULTS: Two hundred and three RAPN and 76 OPN were
      extracted. Patients' demographics and tumors' characteristics were comparable
      between the groups. Blood loss (200 vs. 300 cc, P < 0.0001), intraoperative
      transfusion rates (3% vs. 15.8%, P < 0.001), and length of stay (3 vs. 5 days, P
      < 0.01) were lower for RAPN. A significant decrease in estimated glomerular
      filtration rate was observed from preoperative to postoperative period,
      regardless the approach (OPN, P = 0.026 vs. RAPN, P = 0.014). Conversion to
      radical nephrectomy was 7.8% and 5.9% for OPN and RAPN, respectively. At
      multivariable regression, open approach was predictive of intraoperative
      transfusion and reoperation. Overall actuarial rate of recurrence or metastasis
      was 4.3%, with 3 cancer-related deaths occurring after a median follow-up of 25
      months. No differences were found between the groups. CONCLUSION: In our large
      single-institutional series of patients who underwent partial nephrectomy for
      highly complex renal tumors, robotic approach appeared to be a valuable
      alternative to OPN, with the advantages of reduced blood loss, ischemia time,
      transfusions rate, and length of stay.

PMID- 30100113
TI  - Participation narratives of Third Age adults: Their activities, motivations and
      expectations regarding civil society organisations.
AB  - Third Age adults leaving the labour market are not only armed with broad
      experience and multiple competencies but also find themselves free of
      professional obligations while still physically sound. The general theory of
      Third Age of Laslett sheds a new light on characteristics of ageing adults and
      their role in society. They are able to engage in society in ways inaccessible to
      previous generations of older adults. According to Laslett, combining a myriad
      personal strengths and being free of professional obligations they are challenged
      to make Third Age a time of personal development by making choices of engagement
      and civic contribution. To enlighten these issues, this qualitative study focuses
      on how and under what conditions 23 Third Agers invest their strengths in unpaid
      societal and social participation. Their narratives reveal three types of
      involvement: holistic, inhibited and social consumerist. The holistic pattern
      and, to a lesser extent, the inhibition pattern meet the expectations of Laslett
      about the Third Age. The social consumerist pattern, on the other hand, rather
      refers to disengagement. These observations imply that to facilitate the societal
      engagement and social participation of this population, civil society
      organisations need to rethink their goals, activities and procedures.

PMID- 30100112
TI  - Active ageing in Denmark; shifting institutional landscapes and the intersection
      of national and local priorities.
AB  - Studies of governance rarely examine how specific institutional configurations
      are designed to target specific 'problem' groups, including older adults via
      'active ageing' policies. In Denmark, active ageing policy has been contoured by
      the Structural Reform of 2007, which drove changes in institutional landscapes at
      both national and local levels. Rather than representing a 'hollowing out' of
      control from the centre, the Danish Structural Reform comprised a decentralised
      re-territorialisation of welfare provision, giving the state additional fiscal
      powers whilst placing additional responsibility for welfare delivery at the
      municipal level. The introduction of 'Activity Centres' for older citizens in
      Copenhagen is an exemplar of this change. Here, the provision of sport and
      exercise to older citizens was driven by neoliberal consumer logic and demand for
      self-determination. Yet local services are delivered with communitarian goals and
      methods which directly incorporate service end-users in governance and decision
      making processes. Older citizens are thus empowered to define meaningfulness in
      activities, but only as an active member of a community. Participants are
      conceptualised simultaneously as both consumer and voluntary promoter/supporter
      of active lifestyles within that community. 'Open access' to activity programmes
      is sought, but participation requires membership. Free choice is emphasized, yet
      activity programmes are designed according to group consensus and available
      resources. Claims to cater for the entire older population sit alongside a lower
      age limit of 65 years and the stated aim of ensuring citizens remain free of
      reliance upon municipal services. Activity Centres therefore represent an
      autonomization of responsibility for health maintenance among older citizens,
      whilst concurrently reflecting new techniques of arms-length state governance of
      their behaviour.

PMID- 30100114
TI  - "No Regrets": Qualitative Evidence on Early Claiming of Social Security
      Retirement.
AB  - We conducted focus groups (n = 68) to explore how older Americans feel about
      their past Social Security claiming decisions. Like most older Americans, our
      focus group participants claimed Social Security early: about 45% claimed Social
      Security at age 62, and about 65% claimed before Full Retirement Age (ages 65
      66). We might expect that older adults may regret early claiming, since this can
      result in lower financial security in later life. Respondents reported
      satisfaction with their decisions to claim relatively early. Most noted that they
      "made the right decision given their circumstances at the time." Reasons for the
      decision included liquidity constraints and longevity concerns. People reported
      that were circumstances different they would have chosen to claim later. We also
      found evidence that having more information and being better prepared at the time
      of claiming increased satisfaction levels.

PMID- 30100115
TI  - Resisting decline? Narratives of independence among aging limbless veterans.
AB  - 'Maintaining independence' is a core project for many older people; a project
      which has received critical attention within aging studies. In this paper, we
      extend the critique by exploring how aging intersects with disability and
      militarism as additional critical subjectivities. The empirical focus of the
      paper is the narratives of older military veterans who had lost a limb either
      during or post-service. Data reveal the long legacy of military experience in the
      lives of these veterans; a legacy which is manifested in both negative and
      positive outcomes. A dominant narrative of 'struggling against decline' is
      identified, while 'minimization', 'victimhood', and 'life-as-normal' emerged as
      further narrative types through which veterans articulated their experiences of
      aging with limb loss. Findings from this study highlight both resilience and
      vulnerability as features of older veterans' experiences of aging with limb loss.
      Building on previous critiques, we add further nuance to understandings of how
      older people might respond to the narrative of decline, and illustrate multiple
      possible meanings of claims to 'normality'. By sharing the stories of older
      limbless veterans, we aim to contribute to - and connect - several fields of
      study including aging studies, critical disability studies, and critical military
      studies. Findings are discussed in light of current trends in each of these
      fields.

PMID- 30100116
TI  - Themes of care giving and receiving in the interconnecting stories of a mother
      living with dementia and her adult son: A single-case life story study.
AB  - Life story work is generally regarded as a way for people living with dementia to
      maintain their connection with the past and facilitate meaningful communication
      in the present. This paper presents a single-case life story study that
      highlights themes of care giving and receiving in the interconnecting stories of
      a mother living with dementia and her adult son. The project methodology was
      informed by ideas and practices from both drama therapy and narrative therapy
      and, as such, combined a performative approach to life story work with a
      creative, collaborative approach to communication. The work is discussed in light
      of recent conversations about citizenship and dementia (Baldwin, 2008; Baldwin &
      Greason, 2016; Brannelly, 2016) that highlight the essential interdependence of
      people's lives and narratives as justification for more egalitarian relationships
      between people living with dementia and their partners in care.

PMID- 30100117
TI  - The role of alcohol in baby boomers' biographical accounts.

PMID- 30100118
TI  - Tired, but not (only) because of age: An interactional sociolinguistic study of
      participants' variable stances towards older-age categorial explanations in
      everyday hair-salon talk.
AB  - A growing body of research examining age-in-interaction has revealed the way in
      which people orientate to stereotypical associations of aging. However,
      relatively little attention has been given to the way older-age categorial terms
      and expressions are used in everyday, non-medicalised settings and the kinds of
      identities thereby achieved. In this study I aim to bring to the fore and explain
      the variability of stances towards older-age terms and expressions in an ordinary
      setting, a hair-salon. I explore this variability by scrutinizing in detail cases
      where older women resist another's use of aging to explain their ailment or
      complaint, and contrast these with cases where the same women, in the same
      appointment, themselves invoke older age to explain or intensify their own
      problem. Drawing on audio-recorded conversations between clients and salon
      workers and using the micro-discourse analytic tools of Conversation Analysis and
      Membership Categorization Analysis, I show that these seemingly inconsistent
      orientations to older age emerge out of the unfolding sequential context and the
      different projects in which participants are engaged in interaction. I further
      show that older age is not the only or main identity orientated to in such uses
      in this setting. The discussion as a whole highlights the value of adopting an
      age-blind approach to the data and of examining people's use of older-age terms
      and expressions in a range of ordinary settings.

PMID- 30100119
TI  - God's waiting room: The rise and fall of South Beach as an unplanned retirement
      community, 1950-2000.
AB  - Between 1950 and 1980, South Beach, at the southern tip of Miami Beach, was
      transformed into an unplanned retirement community by the arrival of thousands of
      elderly, poor, mainly Jewish in-migrants. South Beach seniors had a profound
      impact on the local economy and became a dominant force in city politics,
      profoundly altering perceptions of what was formerly a tourist resort. After
      1980, the elderly population of South Beach declined rapidly and effectively
      disappeared by the turn of the century. This essay traces the rise and fall of
      South Beach as a large-scale, informal, voluntary, urban retirement enclave to
      show how key features of the political economy of cities in the United States may
      frustrate the aspirations of environmental gerontology to enlist municipal
      governments in the effort to provide desirable options for aging-in-the-right
      place to a broad socio-economic range of seniors.

PMID- 30100120
TI  - Social and organizational practices that influence hospice utilization in nursing
      homes.
AB  - Hospice has grown considerably but the likelihood that someone gets hospice
      depends on social and organizational practices. This article shows how staff
      beliefs and work routines influenced hospice utilization in two nursing homes. In
      one, 76% of residents died on hospice and in the other 24% did. Staff identified
      barriers to hospice including families who saw hospice as giving up and gaps in
      the reimbursement system. At the high-hospice nursing home, staff said hospice
      care extended beyond what they provided on their own. At the low-hospice nursing
      home, an influential group said hospice was essentially the same as their own end
      of-life care and therefore needlessly duplicative. Staff at the high-hospice
      nursing home proactively approached families about hospice, whereas staff at the
      low-hospice nursing home took a reactive approach, getting hospice when families
      asked for it. Findings demonstrate how staff beliefs and practices regarding
      hospice shape end-of-life care in nursing homes.

PMID- 30100121
TI  - On the move in search of health and care: Circular migration and family conflict
      amongst older Turkish immigrants in Germany.
AB  - This study focuses on circular migration amongst older Turkish immigrants to
      investigate two main questions: (1) How do perceived health and available
      healthcare systems in Turkey and Germany determine the structure of circular
      migration? (2) How is eldercare shaped by intergenerational conflict and exchange
      relations amongst older immigrants, their adult children in Germany, and their
      extended families in Turkey? Through the analysis of 40 in-depth interviews, this
      study finds that while Turkey offers healthier physical, psychological, and
      religious options, older circular migrants are more drawn to Germany because they
      perceive its healthcare system to be superior. Furthermore, contrary to
      conventional accounts, eldercare has mostly been navigated through
      intergenerational conflict and exchange relations, instead of family solidarity
      or traditional filial roles, and these conflicts and exchange principles around
      eldercare regulate family living arrangements across the two countries. In short,
      older Turkish immigrants encounter unique challenges in both their home and host
      countries, which promulgates their circular migration.

PMID- 30100122
TI  - The emergence of the creative ager - On subject cultures of late-life creativity.
AB  - OBJECTIVES: In the last fifteen years, research on aging has seen a new interest
      in creativity in later life. While late-life creativity has often been described
      as a method to unpack the potential of older adults in the face of demographic
      change, this newfound interest is arguably linked to the commodification of late
      life creativity itself in terms of innovation and productivity. These new modes
      of creativity might then also establish new ways to age. Has the homo aestheticus
      spread into old age? METHOD: To explore this question, this paper first lays out
      a praxeology of late-life creativity. In this framework, creativity as well as
      age is understood as a social practice through which the artwork as well as the
      (older) artist is continuously produced. Second, this paper draws upon data from
      thirteen semi-structured interviews with older adults regularly involved in
      creative practices in their everyday lives. Using the documentary method, data
      shows how older adults describe the creative practice and what meanings they
      attach to growing older within these practices. RESULTS AND DISCUSSION: Analyzing
      subject cultures that emerge from creativity in later life shows how creative
      practice calls for a specific self-image that is centered around productivity,
      the preservation of field positions despite growing older and active as well as
      anti-aging. Studying late-life creativity through a praxeological lens allows for
      critically evaluating current modes of creativity and the normative positions
      that are inherent in these practices.

PMID- 30100123
TI  - Editorial overview: Molecular and genetic basis of [metabolic] disease: Genes,
      glucose, glycerol and girth: metabolism in our DNA.

PMID- 30100124
TI  - [Image guided radiation therapy for prostate cancer; how, when and why?]
AB  - Novel techniques of prostate cancer radiotherapy require increased precision,
      which is allowed by Image Guided Radiation Therapy (IGRT), using fiducial markers
      and orthogonal radiographs, cone beam computed tomography, magnetic resonance
      imaging, ultrasound, and/or transponders. IGRT may reduce the toxicity of
      radiation therapy, but there is no clear recommendation on the best IGRT
      technique and how often it should be applied.

PMID- 30100125
TI  - [Recent data in cervical cancer: Radiation oncologist's perspective].
AB  - During the recent past years, the therapeutic management of locally advanced
      cervical cancer patients has consistently improved, with the integration of image
      guided brachytherapy and dose escalation strategies leading to an improvement of
      local control rates. In parallel, the evolution of external beam radiotherapy
      techniques and the better control of organs at risk doses in brachytherapy have
      contributed to decrease the probability of severe normal tissue complication. In
      case of advanced disease, patients prognosis remains however marked by a high
      risk of distant failure, and this finding has encouraged the assessment of
      various research pathways in order to better predict and/or prevent tumor
      relapse. Major studies are being conducted or have been published, and the place
      of chemoradiation and brachytherapy has been confirmed as first intent treatment
      in case of locally advanced disease. Numerous prospective or retrospective data,
      few of which are reviewed there, have been integrated as part of a strategy aimed
      at being more and more personalized. Next steps of therapeutic optimization will
      include the assessment of multiparameters radiological tools, but will also rely
      on a better understanding of radiobiological pathways involved in local or
      systemic response to irradiation, and the most promising of those is probably the
      anti-tumor immune response.

PMID- 30100126
TI  - [Role of radiation therapy in the management of pancreatic cancer].
AB  - At diagnosis, about 15% of patients with pancreatic cancer present with a
      resectable tumour, 50% have a metastatic tumour, and 25% a locally advanced tumor
      (non-metastatic but unresectable due to vascular invasion) or borderline
      resectable. Despite the technical progress made in the field of radiation therapy
      and the improvement of the efficacy of chemotherapy, the prognosis of these
      patients remains very poor. Recently, the role of radiation therapy in the
      management of pancreatic cancer has been much debated. This review aims to
      evaluate the role of radiation therapy for these patients.

PMID- 30100127
TI  - Efficacy of Cognitive Behavioral Therapy in Adherence to the Mediterranean Diet
      in Metabolic Syndrome Patients: A Randomized Controlled Trial.
AB  - OBJECTIVE: Verify the efficacy of cognitive behavioral therapy (CBT) in adherence
      to the Mediterranean diet (MedDiet) in metabolic syndrome (MetS) patients.
      DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: In the Multimodal Intervention
      Program for Patients with Metabolic Syndrome clinical trial, 79 MetS patients
      completed the intervention. Of those, 48 belonged to the experimental group and
      31 to the control group. The intervention received by the experimental group was
      CBT; the control group followed usual care and attended a workshop on healthy
      lifestyle. MAIN OUTCOME MEASURE(S) AND ANALYSIS: Anthropometric, biochemical,
      psychological, and lifestyle measures were taken before and after the
      intervention at 3 and 6 months. Analyses included paired t tests, ANOVA, and
      ANCOVA. RESULTS: The ANOVA results showed a statistically significant interaction
      between the 2 groups in waist circumference (P = .009), triglycerides (P = .015),
      and adherence to the MedDiet (P = .026). The ANCOVA results indicated between
      group difference in waist circumference (P = .026 and .062 at 3 and 6months,
      respectively), in triglycerides (P = .009 and .860 at 3 and 6 months,
      respectively), and in MedDiet (P = .024 and .273 at 3 and 6 months,
      respectively). CONCLUSIONS AND IMPLICATIONS: In interventions in which CBT was
      applied, significant improvements were observed in MetS patients, especially in
      adherence to the MedDiet.

PMID- 30100128
TI  - Traditional Korean medicine treatment for livedoid vasculopathy: Five case
      reports.
AB  - INTRODUCTION: This study was performed to evaluate the clinical effect of a
      Korean medicine treatment for livedoid vasculopathy (LV). METHODS: Five patients
      with LV were selected who exhibited blood stasis due to qi stagnation () caused
      by external cold () or dual deficiency of qi and blood () and who had suffered
      from chronic episodic LV for at least 2 years. The treatment consisted of Korean
      herbal medicine, Haechungtang (, HC). Five cases were evaluated based on visual
      symptoms. The symptoms at first visit were scored on a visual analogue scale
      (VAS) from 1 to 10. RESULTS: Following treatment, all of the symptoms except
      pigmentation disappeared completely in all cases. No symptom control with
      corticosteroids or warfarin was necessary. CONCLUSION: These case reports suggest
      that HC could be effective for treating LV. Follow-up studies and further
      clinical studies are needed to evaluate recurrence and to provide more efficient
      treatment.

PMID- 30100129
TI  - Add-on Effect Of Hot Sand Fomentation To Yoga On Pain, Disability, And Quality Of
      Life In Chronic Neck Pain Patients.
AB  - BACKGROUND: Neck pain is one of the commonest complaints and an important public
      health problem across the globe. Yoga has reported to be useful for neck pain and
      hot sand has reported to be useful for chronic rheumatism. The present study was
      conducted to evaluate the add-on effect of hot sand fomentation (HSF) to yoga on
      pain, disability, quality of sleep (QOS) and quality of life (QOL) of the
      patients with non-specific neck pain. MATERIALS AND METHODS: A total of 60
      subjects with non-specific or common neck pain were recruited and randomly
      divided into either study group or control group. Both the groups have received
      yoga and sesame seed oil (Sesamum Indicum L.) application. In addition to yoga
      and sesame seed oil, study group received HSF for 15 min per day for 5-days.
      Assessments were taken prior to and after the intervention. RESULTS: Results of
      the study showed a significant reduction in the scores of visual analogue scale
      for pain, neck disability index (NDI), The Pittsburgh Sleep Quality Index (PSQI),
      and a significant increase in physical function, physical health, emotional
      problem, pain, and general health both in study and control groups. However,
      reductions in pain and NDI along with improvement in social functions were better
      in the study group as compared with control group. CONCLUSION: Results of this
      study suggest that addition of HSF to yoga provides a better reduction in pain
      and disability along with improvement in the social functioning of the patients
      with non-specific neck pain than yoga alone.

PMID- 30100130
TI  - Situating the syringe.
AB  - What's at stake when the syringe becomes a tool for thinking? Reflecting on the
      production of Social Science of the Syringe, this commentary describes the
      empirical challenges of encountering injecting drug users directly affected by
      Harm Reduction policies as significant stakeholders in the expression of drug
      problems.

PMID- 30100131
TI  - Erratum to "Using best expert judgement to harmonise marine environmental status
      assessment and maritime spatial planning" [Mar. Pollut. Bull. 133(2018) 367-377].

PMID- 30100133
TI  - Patient Outcomes After Total Knee Arthroplasty in Patients Older Than 80 Years.
AB  - BACKGROUND: Patients aged 80 and above who suffer from end-stage osteoarthritis
      may benefit from total knee arthroplasty (TKA), but at high potential risk.
      Additionally, there is controversy about whether functional improvement in
      patients above age 80 is similar to younger patients. We compared functional
      improvement, length of stay (LOS), and facility discharge rates after TKA between
      this cohort and patients less than 80 years of age. METHODS: We completed a
      retrospective cohort study comparing TKA patients aged 80 and above with all
      patients younger than 80. We utilized data from a prospectively collected
      institutional repository of 2308 TKAs performed from April 2011 through July 2016
      at an academic medical center in the United States. We performed multivariable
      logistic regression to determine the association between age group and clinically
      significant improvement in the Patient-Reported Outcome Measurement Information
      System (PROMIS)-10 physical component summary (PCS) score. Secondary outcomes
      included the magnitude of PCS change, LOS, and facility discharge. RESULTS: There
      were 175 (7.6%) TKAs in patients older than 80 years compared with 2133 TKAs in
      patients younger than 80. Patients over 80 had similar adjusted odds of achieving
      clinically significant PCS improvement following TKA (P = .366), and there was no
      statistical difference in adjusted postoperative PCS improvement between the 2
      age groups. Age 80 and above was associated with a longer adjusted LOS and
      demonstrated increased odds of facility discharge (odds ratio 4.11, P < .001)
      after TKA. CONCLUSION: Following TKA, patients older than 80 years demonstrate
      similar adjusted functional improvement in comparison to younger patients.
      However, older patients did require substantially more resources as they remained
      in the hospital longer and were discharged to rehabilitation more often.

PMID- 30100132
TI  - Obesity-associated severe asthma in an adult Japanese population.
AB  - BACKGROUND: Severe asthma is increasingly being recognized as an important public
      health issue. Obesity has been identified as a risk factor for poor asthma
      control and for worsening of asthma severity. However, most studies investigating
      obese patients with asthma have been performed in Western countries. Reports on
      the characteristics of obese Japanese individuals with severe asthma are lacking.
      Herein, we investigated the clinical characteristics of patients with obesity
      associated severe asthma in a Japanese population and the association between
      obesity and poor asthma control. METHODS: We conducted a retrospective
      observational study of adult patients with severe asthma. Patients were
      classified into two groups based on the definition of obesity recommended by the
      Japan Society for the Study of Obesity: obese (OB) group (body mass index [BMI]
      >=25 kg/m2) and non-obese (NOB) group (BMI <25 kg/m2). The two groups were
      compared. The characteristics of obesity and the metabolic functions are known to
      differ between males and females; therefore, we analyzed male-only and female
      only cohorts separately. RESULTS: A total of 492 patients were enrolled. Age,
      smoking history in terms of number of pack-years, daily controller medications
      use, and spirometric data were not significantly different between the OB and NOB
      groups in either cohort. In the female cohort, the annual exacerbation ratio and
      the percentage of frequent exacerbators were significantly higher in the OB group
      compared to the NOB group. A multivariate logistic regression analysis showed
      that obesity was independently associated with frequent asthma exacerbations in
      the female cohort. CONCLUSIONS: Our study revealed that obesity, defined as a BMI
      >=25 kg/m2, was independently associated with poor asthma control (including
      acute exacerbations) in adult Japanese females with severe asthma.

PMID- 30100134
TI  - Diagnosing Periprosthetic Joint Infection in Inflammatory Arthritis: Assumption
      Is the Enemy of True Understanding.
AB  - BACKGROUND: Despite concern over the interpretation of serum and synovial fluid
      tests to screen and diagnose periprosthetic joint infection (PJI) in patients
      with inflammatory arthritis, only a single study has investigated this area. We
      aimed to assess accuracy of clinical and laboratory markers for PJI diagnosis in
      the context of underlying inflammatory arthritis. METHODS: This multicenter study
      was conducted on total joint arthroplasty patients at 3 different centers between
      2001 and 2016. PJI was defined based on Musculoskeletal Infection Society
      criteria. Acute PJI cases were excluded. Patients operated for a diagnosis other
      than infection, who did not subsequently fail at 1-year follow-up, were
      considered aseptic revisions. Serum C-reactive protein and erythrocyte
      sedimentation rate, synovial white blood cell and differential, as well as alpha
      defensin and results of frozen section were documented. RESULTS: In total, 1220
      patients undergoing revision total joint arthroplasty (567 PJI, 653 aseptic) were
      included. Fifty-five septic patients and 61 in the aseptic group had inflammatory
      arthritis. Although mean levels of serum C-reactive protein and synovial white
      blood cell in inflammatory arthritis patients were significantly higher compared
      to patients without inflammatory arthritis, there were no significant differences
      in PJI patients. The thresholds associated with increased risk for PJI in
      patients with and without inflammatory arthritis were similar and closely
      resembled traditional cut-points. CONCLUSION: We demonstrate higher baseline
      immune upregulation in aseptic revision cases with inflammatory arthritis, but no
      significant differences are seen for PJI. Conventional PJI thresholds for serum
      and synovial diagnostic markers should be adhered to. Assumptions about
      inflammatory arthritis patients needing differential diagnostic protocols should
      be avoided.

PMID- 30100135
TI  - Patients With Infected Total Hip Arthroplasty Undergoing 2-Stage Exchange
      Arthroplasty Experience Massive Blood Loss.
AB  - BACKGROUND: Two-stage exchange arthroplasty is the preferred treatment for
      chronic periprosthetic joint infection following total hip arthroplasty (THA).
      These patients are at high risk of substantial blood loss and perioperative blood
      transfusion. Our study aimed at determining risk factors for blood transfusion
      during a 2-stage exchange for infected THA. METHODS: Medical records of 297
      patients with infected THA who underwent 2-stage exchange arthroplasty from 1997
      to 2016 were reviewed. Blood loss was calculated using a validated formula.
      Transfusion data, clinical information, and operative data were gathered to
      determine predictors of blood loss and risk factors for perioperative allogeneic
      blood transfusion. RESULTS: Calculated blood loss was significantly higher during
      reimplantation than resection arthroplasty (5156.0 +/- 3402 mL vs 3706.9 +/- 2148
      mL; P < .0001). Blood transfusion was needed in 81% after resection and 81.1%
      after reimplantation. Allogeneic blood transfusion averaged 3.6 +/- 1.8 units for
      stage 1 and 4.2 +/- 2.9 units for stage 2 (P = .0066). Patient characteristics
      that increased the likelihood for perioperative blood transfusions were
      increasing preoperative international normalized ratio, type 2 diabetes, current
      smoking, age, and transfusion requirement in the first stage. Tranexamic acid
      usage was associated with decreased blood loss. CONCLUSION: Patients with
      periprosthetic joint infection following THA have significant blood loss during
      both stages of exchange arthroplasty, especially reimplantation. Hematological
      optimization should be considered in all patients requiring a transfusion after
      the first stage, as these patients are at greater risk of requiring transfusion
      after the second stage. The use of tranexamic acid dramatically decreases the
      risk of requiring a transfusion in both stages and should be more ubiquitously
      incorporated into blood management protocols.

PMID- 30100136
TI  - Head Taper Corrosion Causing Head Bottoming Out and Consecutive Gross Stem Taper
      Failure in Total Hip Arthroplasty.
AB  - BACKGROUND: Taper corrosion in total hip arthroplasty for bearings with metal
      heads against polyethylene has developed from an anecdotal observation to a
      clinical problem. Increased taper wear and even gross taper failure have been
      reported for one particular design. It is hypothesized that corrosion of the
      female head taper results in taper widening, allowing the cobalt-chromium head to
      turn on the stem and wear down the softer titanium alloy by abrasive wear,
      ultimately causing failure. The purpose of this study is to investigate the time
      course of this process and the general role of taper dimensions and material in
      this problem. METHODS: Retrieved cobalt-chromium alloy heads (n = 30, LFIT;
      Stryker, Mahwah, NJ) and Ti-12Mo-6Zr-2Fe (TMZF) stems (n = 10, Accolade I;
      Stryker) were available for analysis. Taper material loss was determined using
      three-dimensional coordinate measurements and scanning. The pristine tip
      clearance between head and stem was analytically determined. The influence of
      taper material and taper size on taper deformation and micromotion was
      investigated using a finite element model. RESULTS: Material loss at the head
      taper increased with time in situ up to a volume of 20.8 mm3 (P < .001). A mean
      linear material loss above 76 MUm at the head taper was analytically confirmed to
      result in bottoming out, which was observed in 12 heads. The finite element
      calculations showed significantly larger deformations and micromotions for a
      small 11/13 TMZF taper combined with a distinctly different micromotion pattern
      compared to other materials and taper designs. CONCLUSION: A 11/13 TMZF taper
      design with 36-mm head diameters bears a higher risk for corrosion than larger
      tapers made from stiffer materials. Failures of this combination are not
      restricted to the head sizes included in the recall. Patients with this implant
      combination should be closely monitored.

PMID- 30100137
TI  - Defining Treatment Success After 2-Stage Exchange Arthroplasty for Periprosthetic
      Joint Infection.
AB  - BACKGROUND: Two-stage exchange arthroplasty remains the preferred surgical
      treatment method for patients with chronic periprosthetic joint infection (PJI).
      The success of this procedure is not known exactly as various definitions of
      success have been used. This study aimed at analyzing the difference in outcome
      following 2-stage exchange arthroplasty using different definitions for success.
      METHODS: A retrospective study of 703 patients with PJI who underwent resection
      arthroplasty and spacer insertion between January 1999 and June 2015 was
      performed. Chart review identified intraoperative cultures at the time of spacer,
      reimplantation, and any subsequent reinfections or surgeries following spacer
      insertion. After applying the exclusion criteria, a total of 570 patients were
      included in the analysis. Five definitions of treatment success were assessed:
      (1) Delphi consensus success, (2) modified Delphi consensus success, (3)
      microbiological success, (4) implant success, and (5) surgical success. RESULTS:
      Of the 570 patients with PJIs, 458 were reimplanted at a mean of 4.1 months.
      Mortality was 13.9% with 6.7% occurring before reimplantation. Treatment success
      was highly variable depending on the definition used (54.2%-88.9%). In 19.6% of
      PJI cases, the Delphi consensus definition could not be assessed as
      reimplantation never occurred. Furthermore, 67.0% of these patients underwent
      reoperations, which may not be accounted for in the Delphi consensus definition.
      CONCLUSION: Treatment success rates vary dramatically depending on the definition
      used at our institution. We hope these definitions can help bring forth awareness
      for standardized reporting of outcomes, but further validation and agreement of
      these definitions among surgeons and infectious disease physicians is crucial.

PMID- 30100138
TI  - Evaluation of the effect of relaxation therapy in patients with arterial
      hypertension.
AB  - OBJECTIVES: To evaluate whether the application of a relaxation therapy reduces
      the blood pressure in hypertensive patients and whether there is improvement in
      several parameters which can influence blood pressure such as anxiety, quality of
      life and sleep. METHODS: A quasi-experimental study (measures before-after) was
      performed in 25 Primary Care patients with hypertension poorly controlled by
      pharmacological treatment. The intervention consisted of relaxation therapy
      composed of 3techniques: passive relaxation of Schwartz-Haynes, diaphragmatic
      breathing and imaginary visualization. A total of 14 group sessions of 30min each
      (2/week) were conducted. Systolic and diastolic blood pressure were taken at the
      beginning and end of the relaxation programme implemented and after each of the
      programme sessions. The Pittsburgh Sleep Quality, Quality of Life Hypertension,
      State-Trait Anxiety and Perceived Stress questionnaires were used to measure
      psychosocial parameters. RESULTS: After intervention, a reduction in systolic
      blood pressure of 20mmHg (p<.001) and of 8mmHg (p<.001) in diastolic blood
      pressure was observed. Regarding other factors, sleep quality (p<.001), quality
      of life (p<.001) and state anxiety (p=.004) were significantly improved.
      CONCLUSIONS: Relaxation therapy had positive effects in improving blood pressure
      parameters, as well as the other factors evaluated. In our opinion, such
      strategies should be evaluated more thoroughly to consider their inclusion in
      Primary Care.

PMID- 30100139
TI  - Psychological consequences of the restriction of abortion: Analysis and
      implications for practice.

PMID- 30100140
TI  - Urethral reconstruction in patients previously treated with MemokathTM urethral
      endoprosthesis.
AB  - PURPOSE: To evaluate the role and success rate of urethral reconstruction in
      patients with urethral stricture previously treated with thermos-expandable
      MemokathTM urethral endoprosthesis. MATERIALS AND METHOD: A case series of
      patients with urethral stricture and MemokathTM endoprosthesis treated with
      urethroplasty is presented. Reconstruction was decided due to stricture
      progression or complications derived from primary stent treatment. Age, stricture
      and stent length, time between stent placement and urethroplasty, mode of stent
      retrieval, type of urethroplasty, complications and voiding parameters before and
      after urethroplasty were evaluated. Successful outcome was defined as standard
      voiding, without need of any postoperative procedure. RESULTS: Eight cases with
      bulbar urethra stricture were included. MemokathTM was endoscopically retrieved
      before urethroplasty in 6 (75%) and by open urethrotomy at the time of
      urethroplasty in 2 (25%). Technique of urethroplasty was dorso-lateral onlay
      buccal mucosa graft in 5 (62.5%) cases and excision and primary anastomosis,
      anastomotic urethroplasty, and dorsal onlay buccal mucosa graft in one (12.5%)
      case each. There was no failure at 26+/-21.5 months median follow-up. Total IPSS,
      QoL, Qmax and postvoid residual significantly improved (P<.05). The only
      complication presented was epididymitis and penile shortening in one patient
      (12.5%). CONCLUSIONS: Urethroplasty after re-stricture or other complications in
      patients with temporary MemokathTM urethral stent is a viable and definite option
      of reconstruction with excellent results in the short term and few complications.
      One-side dorsolateral onlay buccal mucosa graft augmentation is the optimal
      technique for this indication.

PMID- 30100141
TI  - Usefulness of PET/CT 18-FDG for the diagnosis and follow-up of urological,
      urothelial and kidney tumours.
AB  - INTRODUCTION: New imaging studies have appeared in recent years for the diagnosis
      and follow-up of metastatic urological tumours. MATERIAL AND METHODS: A total of
      41 patients were reviewed with suspected recurrence of a urothelial or kidney
      tumour, analysing the diagnostic performance of PET-CT scans undertaken between
      2013 and 2016. RESULTS: We collected 17 urothelial tumours and 24 renal tumours,
      with a median follow-up of 30 months. A total of 39.3% of the urothelial tumours
      were high grade and 29.3% of the kidney tumours were clear cell Fuhrman II. As a
      whole, the imaging studies detected recurrences in 34 patients. CT was positive
      in 83% of the patients, while the PET scan was positive in 75.6%, CT/PET
      coincidence was 50%. The PET scan detected further disease in 41% of the cases
      compared to 5% by CT. This resulted in a change of therapeutic strategy in 40% of
      the patients. Sensitivity, specificity, positive predictive value and negative
      predictive value for the CT and the PET scans were 92% and 92%, 57% and 100%, 92%
      and 100%, and 57% and 70% respectively. CONCLUSION: The PET scan showed similar
      sensitivity for urological tumours to the standard imaging techniques but with
      higher specificity, positive predictive value and negative predictive value. This
      led to a change in treatment strategy for 40% of the patients in our series. The
      PET scan will probably become the standard test in the extension and follow-up
      studies of most urological tumours.

PMID- 30100142
TI  - A water-filled garment to protect astronauts during interplanetary missions
      tested on board the ISS.
AB  - As manned spaceflights beyond low Earth orbit are in the agenda of Space
      Agencies, the concerns related to space radiation exposure of the crew are still
      without conclusive solutions. The risk of long-term detrimental health effects
      needs to be kept below acceptable limits, and emergency countermeasures must be
      planned to avoid the short-term consequences of exposure to high particle fluxes
      during hardly predictable solar events. Space habitat shielding cannot be the
      ultimate solution: the increasing complexity of future missions will require
      astronauts to protect themselves in low-shielded areas, e.g. during emergency
      operations. Personal radiation shielding is promising, particularly if using
      available resources for multi-functional shielding devices. In this work we
      report on all steps from the conception, design, manufacturing, to the final test
      on board the International Space Station (ISS) of the first prototype of a water
      filled garment for emergency radiation shielding against solar particle events.
      The garment has a good shielding potential and comfort level. On-board water is
      used for filling and then recycled without waste. The successful outcome of this
      experiment represents an important breakthrough in space radiation shielding,
      opening to the development of similarly conceived devices and their use in
      interplanetary missions as the one to Mars.

PMID- 30100143
TI  - The influence of nitrogen concentration and precipitation on fertilizer
      production from urine using a trickling filter.
AB  - Planetary habitation requires technology to maintain natural microbial processes,
      which make nutrients from biowaste available for plant cultivation. This study
      describes a 646 day experiment, in which trickling filters were monitored for
      their ability to mineralize nitrogen when loaded with artificial urine solutions
      of different concentrations (40, 60, 80 and 100% v/v). Former studies have
      indicated that increasing urine concentrations slow nitrogen conversion rates and
      induce growing instability. In the current experiment, nitrogen conversion rates,
      measured as nitrate production/day, did not differ between concentration levels
      and increasing instability was not observed. Instead, the buffering capacity of
      the mussel shells added as buffer system (~75% calcium carbonate) increased with
      increasing concentrations of synthetic urine possibly due to the higher phosphate
      content. The intensified precipitation of calcium phosphates seems to promote
      carbonate dissolution leading to improved buffering. For space applications, the
      precipitation of calcium phosphates is not desirable as for the phosphate to be
      available to the plants the precipitate must be treated with hazardous
      substances. With regard to terrestrial agriculture the process-integrated
      phosphate precipitation is a possibility to separate the macronutrients nitrogen
      and phosphate without addition of other chemicals. Thus, the described process
      offers a simple and cost-effective approach to fertilizer production from
      biogenic residues like slurry.

PMID- 30100144
TI  - Attachment of Turner's thick-toed geckos (Chondrodactylus turneri GRAY 1864)
      during weightlessness and their responses to flotation.
AB  - We investigated the behavior of 15 female Turner's thick-toed geckos
      (Chondrodactylus turneri GRAY 1864) during a 30-day orbital experiment on the
      unmanned spacecraft "BION-M" No. 1. During weightlessness, the geckos maintained
      their ability to attach to the surfaces using the subdigital pads on their toes.
      On average, the geckos spent 99.9% of the time adhering to surfaces during the
      flight and only 0.1% floating freely. The active geckos, when starting to float,
      immediately restored attachment by a number of behavioral responses. The floating
      quiescent geckos, when resuming their active condition, responded in the same
      manner. The responses during flotation are similar to the behavioral reflexes
      triggered by a fall under normal gravity; i.e.: 1) the ventral extension of the
      limbs, 2) a skydiving posture, and 3) postural righting reflexes. Ventral
      extension of limbs was described for the first time in weightlessness. Individual
      variability in the frequency of flotations was found for both active and
      quiescent geckos during the flight. The findings show that the ability to attach
      to surfaces is an important factor in the geckos' adaptation to weightlessness.
      The behavioral responses that originated during freefall in conditions on Earth
      (one-G) appear as adaptations to weightlessness and remain partially effective.

PMID- 30100145
TI  - Feasibility of incorporating all products of human waste processing into material
      cycling in the BTLSS.
AB  - The present study addresses the ways to increase the closure of biotechnical life
      support systems (BTLSS) for space applications. A promising method of organic
      waste processing based on "wet combustion" in hydrogen peroxide developed at the
      IBP SB RAS to produce fertilizers for higher plants is discussed. The method is
      relatively compact, energy efficient, productive, and eco-friendly. However,
      about 4-6 g/L of recalcitrant sediment containing such essential nutrients as Ca,
      Mg, P, Fe, Cu, Mn, and Zn precipitates after the initial process. These elements
      are unavailable to plants grown hydroponically and, thus, drop out of the cycling
      as dead-end products. Possible methods of dissolving that sediment have been
      studied. Results of experiments show that the most promising method is additional
      oxidation of the sediment in HNO3 + H2O2. By using the new technological process,
      which only involves substances synthesized inside the BTLSS material flows, more
      than 90% of each nutrient can be converted into the form available to plants in
      irrigation solutions, thus returning them into the material cycling. The results
      obtained in this study show the efficacy of supplementing the irrigation
      solutions with the mineral nutrients after sediment dissolution. Lettuce plants
      grown as the test object on the newly prepared irrigation solutions produced the
      yield that was more than twice higher than the yield produced on the nutrient
      solutions prepared without the sediment conversion into a soluble form.
      Composition of the gases emitted during this process has been analyzed. Dynamics
      of oxidation of the small fractions of a wax-like sediment remaining after the
      initial sediment dissolution in HNO3 + H2O2 in the BTLSS soil-like substrate has
      been studied. The entire technological scheme aimed at the full inclusion of all
      human wastes into the BTLSS cycling has been suggested and discussed. A process
      scheme of including products of human waste processing in the biotic cycle of the
      BTLSS is discussed in the conclusion.

PMID- 30100146
TI  - The effect of competing risks on astronaut and cosmonaut mortality.
AB  - Astronauts and cosmonauts have been reported to be at substantially lower age
      specific risk of death from chronic disease (primarily heart disease and cancers)
      in comparison to the general populations of the United States and Russia,
      respectively. Yet, both groups have been at greater age-specific risk of death
      from external causes, mainly due to plane crashes and spacecraft accidents. In
      this study we tested the hypothesis that the reported reductions in mortality
      from natural causes result, to some degree, from survival bias created by early
      deaths from external causes. Statistical comparisons of baseline characteristics
      between cause-of-death groups showed no significant differences. Cause-specific
      survival curves showed no difference in long-term mortality from external causes
      among either astronauts or cosmonauts compared to Kaplan-Meier curves with
      censoring for competing causes. Cause-specific survival curves for natural causes
      suggested a possible upward bias in mortality estimates published thus far for
      both groups of space explorers. Differences in survival between Kaplan-Meier
      curves and the cause-specific survival curves were 7% and 5% for astronauts and
      cosmonauts respectively after 55 years. The data do not support the hypothesis
      that observed reductions in mortality from natural causes are due in whole or in
      part to bias created by deaths from external causes at young ages. The data imply
      that reports of cause-specific mortality for astronauts and cosmonauts may in
      fact systematically overestimate mortality rates, though these findings should be
      interpreted with caution as the data are thin at the extremes of follow-up time.

PMID- 30100147
TI  - Procedures for chemical fixation in immunohistochemical analyses of PIN proteins
      regulating polar auxin transport: Relevance to spaceflight experiments.
AB  - The mechanism by which gravity controls the polar transport of auxin, a plant
      hormone regulating multiple physiological processes in higher plants, remains
      unclear, although an important role of PIN proteins as efflux
      carriers/facilitators in polar auxin transport is suggested. We are going to
      study the effect of microgravity on the polar transport of auxin, focusing on the
      cellular localization of its efflux carrier, PsPIN1 in etiolated pea seedlings
      and ZmPIN1a in etiolated maize seedlings grown under microgravity conditions on
      the International Space Station (ISS) using immunohistochemical analyses
      according to space experimental plans (Ueda, 2016). To obtain adequate results
      regarding the cellular localization of functional proteins, prolonged chemical
      fixation processes as well as chemical fixatives should be well-matched to the
      properties of functional proteins as antigens since experimental analyses will be
      performed on the ground after keeping samples for a long duration on the ISS. As
      a result of ground verification, clear detection of the cellular localization of
      PsPIN1 and ZmPIN1a immunohistochemically was successful based on the results of
      several kinds of chemical fixation tested, even when etiolated pea and maize
      seedlings were fixed by immersion in chemical fixative for a long duration. The
      addition of 0.1% (w/v) Nonidet P-40 to chemical fixative composed of 50% (v/v)
      ethanol and 5% (v/v) acetic acid or that of 50% (v/v) methanol and 5% (v/v)
      acetic acid has led to a significant improvement in the immunohistochemical
      detection of PsPIN1 or ZmPIN1a. These chemical fixatives were also shown to be
      storage-stable for a long time before use. In this study, adequate chemical
      fixatives and fixation protocols were developed, which can be used to detect
      localization of PsPIN1 and ZmPIN1a proteins in young etiolated pea and maize
      seedlings, respectively, using anti PsPIN1 and ZmPIN1a antibodies. These
      protocols can be used in spaceflight experiments to investigate the effects of
      the microgravity environment on the ISS on PIN protein localization in pea and
      maize seedlings.

PMID- 30100148
TI  - Spatial resolution requirements for active radiation detectors used beyond low
      earth orbit.
AB  - Measurements of the incident fluence of HZE particles, as a function of LET, are
      used to determine absorbed dose as well as Quality Factors for assigning risk
      estimates to astronauts during manned space missions. These data are often based
      on thin solid state detectors that measure energy deposition, dE, and the
      assumption that the trajectory of the particle, dx, is equivalent to the
      thickness of the detector. Heavy ions often fragment while penetrating shielding
      materials in vehicles or habitats. Projectile fragments can be clustered
      spatially and temporally at the location of the thin detector which are then
      misclassified as a single particle. Eliminating the confounding effects of
      coincident events is the first step in extending the reach of flight instruments
      to identify the charge and velocity of individual particles. Identification of
      individual particles, in a fragmentation spectrum, will require that detection
      systems have sufficient segmentation to eliminate coincident events. The
      objective of this study was to reduce coincident events while avoiding over
      design and complexity. Monte Carlo simulations, using Geant4, were performed for
      4He, 12C, 28Si and 56Fe ions at energies of 300, 900 and 2400 MeV/n incident upon
      aluminum shields having areal densities of 5.4, 13.5, and 54 g/cm2. The identity,
      energy and spatial distribution of all particles downstream from the shielding
      were analyzed using a novel approach based on proximity distributions. Results
      indicated that pixel dimensions on the order of 1 mm were sufficient to reduce
      errors caused by coincident events for active space radiation detectors.

PMID- 30100149
TI  - Comparison of space radiation GCR models to recent AMS data.
AB  - This paper is the third in a series of comparisons of American (NASA) and Russian
      (ROSCOSMOS) space radiation calculations. The present work focuses on calculation
      of fluxes of galactic cosmic rays (GCR), which are a constant source of radiation
      that constitutes one of the major hazards during deep space exploration missions
      for both astronauts/cosmonauts and hardware. In this work, commonly used GCR
      models are compared with recently published measurements of cosmic ray Hydrogen,
      Helium, and the Boron-to-Carbon ratio from the Alpha Magnetic Spectrometer (AMS).
      All of the models were developed and calibrated prior to the publication of the
      AMS data; therefore this an opportunity to validate the models against an
      independent data set.

PMID- 30100150
TI  - A new method for the performance of external chest compressions during
      hypogravity simulation.
AB  - INTRODUCTION: 2015 UK resuscitation guidelines aim for 50-60 mm depth when giving
      external chest compressions (ECCs). This is achievable in hypogravity if the
      rescuer flexes and extends their arms during CPR, or using a new method trialed;
      the 'Mackaill-Russomano' (MR CPR) method. METHODS: 10 participants performed 3
      sets of 30 ECCs in accordance with 2015 guidelines. A control was used at 1Gz,
      with eight further conditions using Mars and Moon simulations, with and without
      braces in the terrestrial position and using the MR CPR method. The MR CPR method
      involved straddling the mannequin, using its legs for stabilization. A body
      suspension device, with counterweights, simulated hypogravity environments. ECC
      depth, rate, angle of arm flexion and heart rate (HR) were measured. RESULTS:
      Participants completed all conditions, and ECC rate was achieved throughout. Mean
      (+/- SD) ECC depth using the MR CPR method at 0.38Gz was 54.1 +/- 0.55 mm with
      braces; 50.5 +/- 1.7 mm without. ECCs were below 50 mm at 0.17Gz using the MR CPR
      method (47.5 +/- 1.47 mm with braces; 47.4 +/- 0.87 mm without). In the
      terrestrial position, ECCs were more effective without braces (49.4 +/- 0.26 mm
      at 0.38Gz; 43.9 +/- 0.87 mm at 0.17Gz) than with braces (48.5 +/- 0.28 mm at
      0.38Gz; 42.4 +/- 0.3 mm at 0.17Gz). Flexion increased from approximately 2
      degrees  - 8 degrees  with and without braces respectively. HR did not change
      significantly from control. DISCUSSION: 2015 guidelines were achieved using the
      MR CPR method at 0.38Gz, with no significant difference with and without braces.
      Participants were closer to achieving the required ECC depth in the terrestrial
      position without braces. ECC depth was not achieved at 0.17Gz, due to a greater
      reduction in effective body weight.

PMID- 30100152
TI  - 42nd COSPAR Assembly.

PMID- 30100151
TI  - Sequencing nothing: Exploring failure modes of nanopore sensing and implications
      for life detection.
AB  - The detection of extant life is a major focus of many planned future planetary
      missions, a current challenge of which is the ability to target biomarkers
      capable of providing unambiguous evidence of life. DNA sequencing is increasingly
      recognized as a powerful tool for life detection for planetary exploration
      missions; beyond use of sequence information to determine the origins of the
      sample (e.g., extant life or forward contamination), recent advances in the field
      have enabled interrogation of single molecules, with or without amplification.
      The focus of this work is on failure modes, specifically the issues encountered
      when there is no-to-low input DNA into a sequencing device, and the potential for
      the generation of sequencing artifacts that could be interpreted as a false
      positive. Using Oxford Nanopore Technologies (ONT) MinION, we assess whether
      single molecule sequencing, involving no amplification, generates noise signals
      that could be misinterpreted in the context of a planetary exploration mission,
      and also whether the ability of the instrument to handle these types of
      situations could make it feasible for clean room monitoring. Utilizing quality
      score filtering techniques in place at the time of this experiment, runs
      containing only initial flowcell chemistry and/or library reagents generated 5
      passing reads out of a total of 3568 measured reads, and contained estimated
      sequences with low complexity that did not map to the NCBI database. The noise
      characteristics in all instances suggest that quality thresholds were
      appropriately chosen by ONT: new chemistry and basecalling workflows have shown
      further suppression of noise sources, which completely mitigate the generation of
      spurious reads.

PMID- 30100153
TI  - Letter to the Editor: Women Representation on Radiology Journal Editorial Boards.

PMID- 30100154
TI  - Assessing Competence in Emergency Radiology Using an Online Simulator.
AB  - RATIONALE AND OBJECTIVES: Traditional assessments in radiology residency focus on
      the Medical Expert CanMEDS role and typically rely upon a single or limited
      static images. We designed an Emergency Radiology Simulator that aimed to assess
      the breadth of competencies required across Medical and NonMedical Expert
      domains. MATERIAL AND METHODS: An online simulator with typical emergency cases
      was administered in October 2015 to Post Graduate Year (PGY) 2-5 residents in
      Radiology. Residents provided preliminary reports, which were graded for style
      and content. The simulation also included prioritization, protocoling,
      counseling, and handover exercises geared to assess NonMedical Expert roles.
      RESULTS: Fourty eight residents participated in the simulation. Level of resident
      was 11 PGY-2, 17 PGY-3, 13 PGY-4, and 7 PGY-5. There was a significant difference
      in resident performance between PGY-2 residents and those more senior in terms of
      the Medical Expert role (findings, diagnosis, recommendations, and clinical
      relevance of reports). Differences in performance between PGY levels were not
      seen in the NonMedical Expert roles (prioritization, protocoling, counseling, and
      handover). CONCLUSION: Simulation provides an opportunity to assess radiology
      resident performance across multiple domains. PGY-2 residents performed worse on
      the Medical Expert domains, although performance did not significantly vary
      between the other years. This may suggest that competence in Emergency Radiology
      is achieved early in residency, possibly related to the importance placed on
      developing skills related to on-call performance during the PGY-2 year. The
      simulator should be extended to other areas of Radiology, in order to assess the
      ability to discriminate performance in other subspecialties.

PMID- 30100155
TI  - Prediction of Cancer Masking in Screening Mammography Using Density and Textural
      Features.
AB  - RATIONALE AND OBJECTIVES: High mammographic density reduces the diagnostic
      accuracy of screening mammography due to masking of tumors, resulting in possible
      delayed diagnosis and missed cancers. Women with high masking risk could be
      preselected for alternative screening regimens less susceptible to masking. In
      this study, various models to predict masking status are presented based on
      biometric and image-based parameters. MATERIALS AND METHODS: For a cohort of 67
      nonscreen-detected (cancers detected via other means after a negative mammogram)
      and 147 screen-detected invasive cancers, quantitative volumetric breast density,
      BI-RADS density, and the distribution and appearance of dense tissue through
      statistical and texture metrics were measured. Age and Body Mass Index were
      recorded. Stepwise multivariate logistic regressions were computed to select
      those parameters that predicted nonscreen-detected cancers. Accuracy of the
      models was evaluated using the area under receiver operator characteristic curve
      (AUC). RESULTS: Using BI-RADS density alone to predict masking risk yielded an
      AUC of 0.64 (95% confidence interval [0.57-0.70]). Age-adjusted BI-RADS density
      or volumetric breast density had AUCs of 0.72 [0.64-0.79] and 0.71 [0.62-0.78],
      respectively. A model extracted from the full pool of variables had an AUC of
      0.75 [0.67-0.82]. CONCLUSION: The optimal model predicts masking more accurately
      than density alone, suggesting that texture metrics may be useful in models to
      guide a stratified screening strategy.

PMID- 30100156
TI  - Moderate Renal Impairment and Toxic Metabolites Produced by the Intestinal
      Microbiome: Dietary Implications.
AB  - OBJECTIVE: Toxic metabolites produced by the intestinal microbiome from animal
      proteins, carnitine (mainly from red meat), or phosphatidylcholine (mainly from
      egg yolk), have important adverse effects on cardiovascular disease. These are
      renally eliminated and may be termed gut-derived uremic toxins (GDUT). We
      hypothesized that even moderate renal impairment and intake of nutrient
      precursors would raise plasma levels of GDUT. DESIGN: A cohort study. SETTING:
      Academic medical center. SUBJECTS: Patients attending stroke prevention clinics
      at a university medical center were recruited. MAIN OUTCOME MEASURE: Nutrient
      intake was assessed by the 131-item Harvard Food Frequency Questionnaire;
      estimated glomerular filtration rate (eGFR) was caculated using the Chronic
      Kidney Disease-Epidemiology (EPI) equations. Plasma levels of trimethylamine n
      oxide, p-cresyl sulfate, hippuric acid, p-cresyl glucuronide, pheny acetyl
      glutamine, and phenyl sulfate were measured by ultra-performance liquid
      chromatography coupled to quadrupole time-of-flight mass spectrometry. RESULTS:
      Among 316 patients recruited, the mean (standard deviation [SD]) age was 66.74
      (10.42) years; 59.7% were men. Mean eGFR was 76.03 +/- 20.01; 57 (18%) had
      eGFR<60 mL/min/1.73 m2. Plasma levels of all GDUT were significantly higher even
      with moderate reduction of eGFR. Nutrient intake affected plasma levels of some
      GDUT; the effects differed by eGFR above and below 60 mL/min/1.73 m2. Plasma
      levels were obtained fasting, so we probably underestimated the effect of
      nutrient intake. CONCLUSIONS: Even moderate impairment of renal function was
      associated with higher plasma levels of GDUT. This has dietary implications for
      patients at risk of atherosclerosis, particularly in those with impaired renal
      function (including the elderly): they should limit intake of animal protein, red
      meat, and egg yolk. It also points the way to novel approaches to vascular
      prevention, including more intensive dialysis, renal transplantation, and
      modification of the intestinal microbiome with probiotics or fecal
      transplantation.

PMID- 30100157
TI  - Relationship of lipoprotein(a) molar concentrations and mass according to
      lipoprotein(a) thresholds and apolipoprotein(a) isoform size.
AB  - BACKGROUND: Lipoprotein(a) [Lp(a)] is reported as Lp(a) particle mass (mg/dL) or
      molar concentration of apolipoprotein(a) [apo(a)] (nmol/L), which is considered
      the gold standard. Values are often converted from one measurement to the other
      but the validity of this is unknown. OBJECTIVES: To quantify the relationship
      between Lp(a) molar concentration and Lp(a) mass in the context of various Lp(a)
      level thresholds and apo(a) isoform size. METHODS: In all samples, Lp(a) levels
      in molar concentration and apo(a) isoform size were determined at the Northwest
      Lipid Metabolism and Diabetes Research Laboratories (NLMDRL). Lp(a) mass levels
      were determined at the University of California, San Diego (UCSD) (1635 samples),
      by 5 commercially available assays: Denka 1 and Denka 2 (each 80 samples), 2
      turbidimetric assays (2545 and 2673 samples, respectively), and an enzyme-linked
      immunosorbent assay (2605 samples). The ratios between Lp(a) molar concentration
      and mass (eg, nmol/L/mg/dL) were calculated and related to apo(a) isoform size.
      RESULTS: The mean (SD) ratios for NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2
      were 2.42 (1.25), 1.64 (0.18), and 2.02 (0.22), respectively. The ratios for
      NLMDRL/UCSD, NLMDRL/Denka1, and NLMDRL/Denka2 increased by Lp(a) cutoffs, with
      ratios of 1.82, 1.52, and 1.87, respectively, for Lp(a) < 75 nmol/L and 2.80,
      1.89, and 2.24, respectively, for Lp(a) > 125 nmol/L. For the commercial
      turbidimetric assays and enzyme-linked immunosorbent assay, the ratios ranged
      from <1 to >5. CONCLUSIONS: Lp(a) molar/mass ratios are threshold, method, and
      isoform dependent. A single conversion factor between assays is not appropriate.
      These data support the transition of Lp(a) mass assays to molar concentration to
      improve diagnostic and clinical interpretation of Lp(a)-mediated risk.

PMID- 30100158
TI  - Metabolic syndrome and its components as risk factors for prolonged corrected QT
      interval in apparently healthy Korean men and women.
AB  - BACKGROUND: Metabolic syndrome (MetS) is clinically important because of its
      association with increased risk of sudden cardiac death, as well as
      cardiovascular disease-related mortality. Data between MetS and prolonged
      corrected QT (QTc) intervals, a useful predictor of sudden cardiac death, are
      limited in apparently healthy adults. OBJECTIVE: This study determined the
      association between MetS and QTc interval in apparently healthy Korean men and
      women. METHODS: We examined the association between MetS and QTc interval in 2157
      Korean adults (1317 men and 840 women) in a health examination program but
      excluded participants with a history of ischemic heart disease, stroke, cardiac
      arrhythmia, cancer, thyroid, respiratory, renal, hepatobiliary, or rheumatologic
      disease. The QTc interval was calculated using Bazett's formula (QTc = QT/?RR).
      Multivariate-adjusted mean QTc values by the number of MetS components were
      calculated after sex stratification and compared using analysis of covariance
      test. RESULTS: The overall prevalence of MetS was 30.5% in men and 19.8% in
      women. The QTc interval positively correlated with age, body mass index, blood
      pressure, fasting plasma glucose, triglycerides, and potassium level in both men
      and women and negatively correlated with calcium and potassium levels and smoking
      status in men. The multivariate-adjusted mean QTc value increased proportionally
      with increasing number of MetS components (P values < 0.001 for both men and
      women). CONCLUSION: We confirmed the arrhythmogenic potential of MetS in
      apparently healthy Korean men and women. These findings suggest that careful
      monitoring of electrocardiography is necessary to evaluate possible arrhythmic
      risk in individuals with MetS.

PMID- 30100159
TI  - Response to Letter to the Editor concerning "Reliability of Foot Posture Index
      individual and total scores for adults and older people".

PMID- 30100160
TI  - Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and
      25 major cancers in 2018.
AB  - INTRODUCTION: Europe contains 9% of the world population but has a 25% share of
      the global cancer burden. Up-to-date cancer statistics in Europe are key to
      cancer planning. Cancer incidence and mortality estimates for 25 major cancers
      are presented for the 40 countries in the four United Nations-defined areas of
      Europe and for Europe and the European Union (EU-28) for 2018. METHODS: Estimates
      of national incidence and mortality rates for 2018 were based on statistical
      models applied to the most recently published data, with predictions obtained
      from recent trends, where possible. The estimated rates in 2018 were applied to
      the 2018 population estimates to obtain the estimated numbers of new cancer cases
      and deaths in Europe in 2018. RESULTS: There were an estimated 3.91 million new
      cases of cancer (excluding non-melanoma skin cancer) and 1.93 million deaths from
      cancer in Europe in 2018. The most common cancer sites were cancers of the female
      breast (523,000 cases), followed by colorectal (500,000), lung (470,000) and
      prostate cancer (450,000). These four cancers represent half of the overall
      burden of cancer in Europe. The most common causes of death from cancer were
      cancers of the lung (388,000 deaths), colorectal (243,000), breast (138,000) and
      pancreatic cancer (128,000). In the EU-28, the estimated number of new cases of
      cancer was approximately 1.6 million in males and 1.4 million in females, with
      790,000 men and 620,000 women dying from the disease in the same year.
      CONCLUSION: The present estimates of the cancer burden in Europe alongside a
      description of the profiles of common cancers at the national and regional level
      provide a basis for establishing priorities for cancer control actions across
      Europe. The estimates presented here are based on the recorded data from 145
      population-based cancer registries in Europe. Their long established role in
      planning and evaluating national cancer plans on the continent should not be
      undervalued.

PMID- 30100161
TI  - Linkage of the ACR National Mammography Database to the Network of State Cancer
      Registries: Proof of Concept Evaluation by the ACR National Mammography Database
      Committee.
AB  - PURPOSE: The National Mammography Database (NMD) contains nearly 20 million
      examinations from 693 facilities; it is the largest information source for use
      and effectiveness of breast imaging in the United States. NMD collects
      demographic, imaging, interpretation, biopsy, and basic pathology results,
      enabling facility and physician comparison for quality improvement. However, NMD
      lacks treatment and clinical outcomes data. The network of state cancer
      registries (CRs) contains detailed pathologic, treatment, and clinical outcomes
      data. This pilot study assessed electronic linkage of NMD and CR data at a
      multicenter institution as proof of concept. MATERIALS AND METHODS: We obtained
      Quality Oversight Committee approval for this retrospective study. Data of
      patients diagnosed with breast cancer in 2014 and 2015 were retrieved from our
      NMD-approved radiology information system (RIS) and matched with reportable
      patients in our CR using social security number (SSN), first name (fname), last
      name (lname), and date of birth (DOB). Matching was repeated without SSN.
      Percentage and reasons for mismatch were evaluated. RESULTS: The RIS query
      identified 1,316 patients. CR linkage was 99.2% successful (n = 1,305 of 1,316)
      using SSN, fname, lname, and DOB. Eleven mismatches included four CR case-finding
      failures, one NMD fname error, five nonreportable in the CR, and one with correct
      identifiers in both databases. Without SSN, linkage was 97.3% successful (n =
      1,281 of 1,316); name errors accounted for 19 and DOB accounted for 5 additional
      mismatches. CONCLUSION: Using common data elements, linkage between the NMD and
      state CRs may be feasible and could provide critical outcomes information to
      advance accurate assessment of breast imaging in the United States.

PMID- 30100162
TI  - Quality Improvements of Veterans Health Administration Radiation Oncology
      Services Through Partnership for Accreditation With the ACR.
AB  - Approximately 20,000 US veterans receive radiation oncology services at a
      Veterans Healthcare Administration (VHA) medical facility each year. They
      currently have access to advanced technologies, which include image-guided
      intensity-modulated radiotherapy, stereotactic radiosurgery, and stereotactic
      body radiation therapy. Although this provides access to cancer therapies that
      are modern, safe, and efficient, the technical complexities of these treatments
      and clinical decision making that goes into the patient selection and
      prescriptions demand quality assurances at each VHA practice. To meet the
      challenges of this need, the VHA established a partnership in 2008 with the ACR's
      Radiation Oncology Practice Accreditation Program (ACR-ROPA). This report
      summarizes the experience of this ongoing partnership and demonstrates the
      combined impact of the VHA's mandate for ACR-ROPA accreditation and internal
      monitoring of all identified corrective actions at each of its radiation oncology
      practices.

PMID- 30100163
TI  - Letter to the Editor Regarding "Voice Tremor in Parkinson's Disease: An Acoustic
      Study" by Gillivan-Murphy et al, In Press in Journal of Voice.

PMID- 30100164
TI  - Talc exposure and risk of stomach cancer: Systematic review and meta-analysis of
      occupational cohort studies.
AB  - Talc powder is widely used in various industries, but the carcinogenic effects
      associated with talc are not well understood. The objective of this study was to
      estimate the risk of stomach cancer after occupational talc exposure. We
      conducted a meta-analysis was performed to calculate the meta-relative risk (mRR)
      of stomach cancer. We searched the MEDLINE, EMBASE, CNKI and Wanfang Data
      databases for publications prior to January 1, 2017 using talc, cancer, and
      mortality as the search terms. Only cohort studies with occupational talc
      exposure and stomach cancer statistics were included. All pooled analyses were
      based on random-effects models. We selected 13 observational studies (12
      publications) for the meta-analysis, and heterogeneity was observed among
      studies. Workers exposed to all forms of talc had a significantly increased mRR
      of 1.21 (95% CI: 1.03-1.42, p = 0.02) for stomach cancer. Workers exposed to talc
      not containing asbestiform fibers also had an increased mRR of 1.26 (95% CI: 0.97
      1.63, p = 0.09). The available data showed a positive association between
      occupational talc exposure and risk of stomach cancer. The association between
      talc not containing asbestiform fibers and risk of stomach cancer was not
      significant. Further epidemiological studies are required to evaluate the safety
      of talc.

PMID- 30100165
TI  - Low mitochondrial DNA copy number of resected cecum appendix correlates with high
      severity of acute appendicitis.
AB  - BACKGROUND/PURPOSE: The roles of mitochondrial DNA alterations in acute
      appendicitis (AA) remain unclear. We evaluated the alterations of mtDNA copy
      number and mtDNA integrity [proportion of mtDNA templates without 8-hydroxyl-2'
      deoxyguanosine (8-OHdG)] of the resected cecum appendixes in clinically suspected
      acute appendicitis (CSAA). METHODS: A total of 228 CSAA patients, including 50
      harbored negative AA (NAA), 155 true AA (TAA) without rupture and 23 TAA with
      rupture, who underwent appendectomies were enrolled. Tissues of resected cecum
      appendixes from the paraffin-embedded pathological blocks were subjected to DNA
      extraction, and their mtDNA copy number and mtDNA integrity were determined by
      quantitative real-time polymerase chain reaction (Q-PCR). RESULTS: During the
      progression of disease severity from NAA to TAA without rupture and further TAA
      with rupture, increases of white blood cell (WBC) counts (p = 0.001), positive
      bacterial culture rates in turbid ascites (p = 0.016) and area (p < 0.001)/or
      volume (p < 0.001) indices of resected cecum appendixes were noted among CSAA
      patients. On the contrary, decrease of mtDNA copy number (p = 0.003) was observed
      during disease progression of CSAA patients, especially in female patients (p =
      0.007). Furthermore, lower mtDNA copy numbers were correlated with higher WBC
      counts (p = 0.001) and larger area (p = 0.003) or volume (p < 0.001) indices of
      the resected cecum appendixes. However, such an alteration was not observed in
      mtDNA integrity of resected cecum appendixes. CONCLUSION: We conclude that a low
      mtDNA copy number of the resected cecum appendix may reflect high severity of
      acute appendicitis.

PMID- 30100167
TI  - Distinct Bone Marrow Sources of Pleiotrophin Control Hematopoietic Stem Cell
      Maintenance and Regeneration.
AB  - Bone marrow (BM) perivascular stromal cells and vascular endothelial cells (ECs)
      are essential for hematopoietic stem cell (HSC) maintenance, but the roles of
      distinct niche compartments during HSC regeneration are less understood. Here we
      show that Leptin receptor-expressing (LepR+) BM stromal cells and ECs
      dichotomously regulate HSC maintenance and regeneration via secretion of
      pleiotrophin (PTN). BM stromal cells are the key source of PTN during steady
      state hematopoiesis because its deletion from stromal cells, but not
      hematopoietic cells, osteoblasts, or ECs, depletes the HSC pool. Following
      myelosuppressive irradiation, PTN expression is increased in bone marrow
      endothelial cells (BMECs), and PTN+ ECs are more frequent in the niche. Moreover,
      deleting Ptn from ECs impairs HSC regeneration whereas Ptn deletion from BM
      stromal cells does not. These findings reveal dichotomous and complementary
      regulation of HSC maintenance and regeneration by BM stromal cells and ECs.

PMID- 30100166
TI  - Tbx6 Induces Nascent Mesoderm from Pluripotent Stem Cells and Temporally Controls
      Cardiac versus Somite Lineage Diversification.
AB  - The mesoderm arises from pluripotent epiblasts and differentiates into multiple
      lineages; however, the underlying molecular mechanisms are unclear. Tbx6 is
      enriched in the paraxial mesoderm and is implicated in somite formation, but its
      function in other mesoderms remains elusive. Here, using direct reprogramming
      based screening, single-cell RNA-seq in mouse embryos, and directed cardiac
      differentiation in pluripotent stem cells (PSCs), we demonstrated that Tbx6
      induces nascent mesoderm from PSCs and determines cardiovascular and somite
      lineage specification via its temporal expression. Tbx6 knockout in mouse PSCs
      using CRISPR/Cas9 technology inhibited mesoderm and cardiovascular
      differentiation, whereas transient Tbx6 expression induced mesoderm and
      cardiovascular specification from mouse and human PSCs via direct upregulation of
      Mesp1, repression of Sox2, and activation of BMP/Nodal/Wnt signaling. Notably,
      prolonged Tbx6 expression suppressed cardiac differentiation and induced somite
      lineages, including skeletal muscle and chondrocytes. Thus, Tbx6 is critical for
      mesoderm induction and subsequent lineage diversification.

PMID- 30100169
TI  - Association of specific meniscal pathologies and other structural pathologies
      with self-reported mechanical symptoms: A cross-sectional study of 566 patients
      undergoing meniscal surgery.
AB  - OBJECTIVES: We explored associations between specific meniscal pathologies and
      other concurrent structural knee pathologies with presence of self-reported
      mechanical symptoms in patients undergoing meniscal surgery. DESIGN: Cross
      sectional study. METHODS: We included patients undergoing surgery for a meniscal
      tear from Knee Arthroscopy Cohort Southern Denmark (KACS). Pre-surgery, patients
      completed online questionnaires including self-reported presence of mechanical
      symptoms. At arthroscopy, surgeons recorded information about specific meniscal
      pathologies and other concurrent structural knee pathologies. Relative risks (RR)
      were estimated to assess associations between specific meniscal pathologies and
      other structural knee pathologies with preoperative mechanical symptoms from
      multivariable logistic regression. RESULTS: 566 of 641 patients (mean age 48.6[SD
      12.9] years, 57% men) with complete data were included. 386 (68%) patients
      reported mechanical symptoms of knee catching/locking and/or extension deficit.
      Most evaluated joint pathologies were not associated with mechanical symptoms of
      any kind with RRs close to 1.0. Meniscal tears involving both the posterior and
      anterior horn (n=22) were associated with knee catching/locking (RR:
      1.49[95%CI:1.15-1.93]), and a tear in both menisci (n=49) was associated with
      extension deficit of the knee (RR: 1.32[95%CI:1.01-1.73]). A partial (n=29) and
      total ACL rupture (n=37) were each associated with extension deficit (RR:
      1.83[95%CI:1.47-2.28] and RR: 1.44[95%CI:1.05-1.98], respectively). CONCLUSIONS:
      Limited associations between specific meniscal pathology and other concurrent
      knee joint pathologies with presence of self-reported mechanical symptoms were
      found in patients undergoing meniscal surgery. The findings question the clinical
      importance of mechanical symptoms as an indicator for arthroscopy for specific
      meniscal tears with the specific aim to relieve such symptoms.

PMID- 30100170
TI  - Injuries among children and adults in alpine skiing and snowboarding.
AB  - OBJECTIVES: To compare the prevalence of injury sites between children and adults
      in alpine skiing and snowboarding. DESIGN: Retrospective comparative study.
      METHODS: The injuries occurring in 14 major Norwegian ski resorts were recorded
      by ski patrols the winter seasons 2010/2011 and 2011/2012. The injuries were
      related to age, equipment and other factors. RESULTS: A total of 1603 injured
      children <=12years and 3202 injured adults >=20years were recorded. The
      prevalence of shoulder injuries was twice as high in adults as in children both
      in alpine skiers (14% vs. 7%) (p<0.001) and snowboarders (20% vs. 10%) (p<0.001).
      Also the prevalence of knee injuries were higher for adults than for children in
      skiing (30% vs. 22%) (p<0.001) as well as in snowboarding (8% for vs. 4%)
      (p=0.009). Both the prevalence of snowboarding wrist injuries and skiing lower
      leg fractures were higher among children than adults (32% vs. 18%, p<0.001 and
      12.6% vs. 3.6%, p<0.001 respectively). More children than adult skiers suffered
      their injuries in terrain parks with 18% vs. 13% (p<0.001). In contrast, more
      adult than child snowboarders (36% vs. 26%) (p=0.007) suffered their injury in
      terrain parks. CONCLUSIONS: The prevalence of shoulder and knee injuries was
      higher in adults than in children both in skiing and boarding. In contrast, the
      prevalence of snowboarding wrist injuries and skiing lower leg fractures were
      higher in children than in adults. More children than adult alpine skiers
      suffered their injury in terrain parks, whereas the reverse was observed for
      snowboarders.

PMID- 30100171
TI  - Reply to comment on "Intra-abdominal actinomycosis resulting in a difficult-to
      diagnose intraperitoneal mass: A case study report".

PMID- 30100168
TI  - Phospho-regulation of ATOH1 Is Required for Plasticity of Secretory Progenitors
      and Tissue Regeneration.
AB  - The intestinal epithelium is largely maintained by self-renewing stem cells but
      with apparently committed progenitors also contributing, particularly following
      tissue damage. However, the mechanism of, and requirement for, progenitor
      plasticity in mediating pathological response remain unknown. Here we show that
      phosphorylation of the transcription factor Atoh1 is required for both the
      contribution of secretory progenitors to the stem cell pool and for a robust
      regenerative response. As confirmed by lineage tracing, Atoh1+ cells
      (Atoh1(WT)CreERT2 mice) give rise to multilineage intestinal clones both in the
      steady state and after tissue damage. In a phosphomutant Atoh1(9S/T-A)CreERT2
      line, preventing phosphorylation of ATOH1 protein acts to promote secretory
      differentiation and inhibit the contribution of progenitors to self-renewal.
      Following chemical colitis, Atoh1+ cells of Atoh1(9S/T-A)CreERT2 mice have
      reduced clonogenicity that affects overall regeneration. Progenitor plasticity
      maintains robust self-renewal in the intestinal epithelium, and the balance
      between stem and progenitor fate is directly coordinated by ATOH1 multisite
      phosphorylation.

PMID- 30100172
TI  - Antifungal and antibacterial activity of densely dispersed silver nanospheres
      with homogeneity size which synthesized using chicory: An in vitro study.
AB  - With increase in isolation of multi and extensive drug resistance hospital
      pathogens (MDR, XDR) in burn centers of many hospitals in the world, attempt to
      use nanomaterials for treatment of burn-infected patients is the focus of
      researches all around the world. In the present investigation silver nanospheres
      (Ag NSs) has been synthesized by chicory seed exudates (CSE). The various
      parameters influencing the mechanism of Ag NSs synthesis including temperature,
      concentration, pH and time were studied. Greener Ag NSs were formed when the
      reaction conditions were altered with respect to pH, concentration of AgNO3 and
      incubation temperature. Finally, we evaluated antimicrobial activity of silver
      nanospheres biosynthesized by chicory (Cichodrium intybus) against most prevalent
      burn bacteria pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae,
      Acinetobacter baumannii, and fungus Fusarium solani. The UV visible spectroscopy,
      X-Ray diffraction (XRD), dynamic light scattering (DLS) used for primary
      screening of physicochemical properties. The transmission electron microscopy
      (TEM) images showed the Ag NSs (with globular shape) with a size less than 25nm
      that they have the same size about 8nm (more than 97% are 8nm). Minimum
      inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Ag
      NSs against the standard strains of A. baumannii, P. aeruginosa and K. pneumonia
      showed a relatively high inhibitory and bactericidal activity (MIC 1.56MUg/mL and
      MBC 3.12MUg/mL) of the nanoparticles and F. solani cultures. In antifungal tests,
      the lowest level of zone of inhibition was observed at a concentration of 5MUg/mL
      synthesized silver nanospheres with the 7% inhibition of growth. Ag NSs have high
      antimicrobial activity against three common burn bacteria pathogens and fungus F.
      solani. Therefore, Ag NSs can be used to prevent burn infection and for wound
      healing.

PMID- 30100173
TI  - Connexin 30.2 is expressed in exocrine vascular endothelial and ductal epithelial
      cells throughout pancreatic postnatal development.
AB  - Previously we have demonstrated that the GJ protein connexin 30.2 (Cx30.2) is
      expressed in pancreatic beta cells and endothelial cells (ECs) of the islet. In
      the present study, we address whether Cx30.2 is expressed in the exocrine
      pancreas, including its vascular system. For this, adult mouse pancreatic
      sections were double labeled with specific antibodies against Cx30.2 and CD31, an
      endothelial cell marker, or with anti-alpha-actin smooth muscle, a smooth muscle
      cell (SMC) marker or anti-mucin-1, a marker of epithelial ductal cells, using
      immunofluorescence (IF) studies. Cx30.2-IF hot spots were found at junctional
      membranes of exocrine ECs and SMCs of blood vessels. Furthermore, Cx30.2 was
      localized in mucin-1 positive cells or epithelial ductal cells. Using
      immunohistochemistry (IHC) studies, it was found that in vessels and ducts of
      different diameters, Cx30.2 was also expressed in these cell types. In addition,
      it was found that Cx30.2 is already expressed in these cell types in pancreatic
      sections of 3, 14 and 21 days postpartum. Moreover, this cell specific pattern of
      expression was also found in the adult rat, hamster and guinea pig pancreas.
      Expression of Cx30.2 mRNA and protein in the pancreas of all these species was
      confirmed by RT-PCR and Western blot studies. Overall, our results suggest that
      intercellular coupling mediated by Cx30.2 intercellular channels may synchronize
      the functional activity of ECs and SMCs of vascular cells, as well as of
      epithelial ductal cells after birth.

PMID- 30100174
TI  - The impact of self-reported preconception body mass index on gestational abnormal
      glucose tolerance in a Chinese center.
AB  - AIMS: To investigate the association between self-reported preconception body
      mass index (BMI) and the risk of abnormal glucose tolerance (AGT). METHODS: Data
      were obtained from a prospective cohort study conducted in China. We recruited
      5305 qualified women who registered during 22-24 gestational weeks. Blood glucose
      was measured by trained professionals, and other health-related information was
      recorded prospectively. We used logistic regression to evaluate the relationship
      between preconception BMI with AGT and its subtypes, after controlling for
      potential confounders. RESULTS: 649 of the 5305 participants (12.2%) were
      diagnosed with AGT. The prevalences of AGT in underweight, normal weight,
      overweight and obese population indicated a significant linear increased trend
      (8.4%, 11.1%, 20.0% and 27.7%, respectively) (p < 0.001), regardless of parity
      status. After adjustment for maternal age, education and parity, the adjusted
      odds ratios of AGT for underweight: OR = 0.82 (95% CI: 0.62, 1.06); overweight:
      OR = 1.92 (95% CI: 1.54, 2.38); obese: OR = 2.82 (95% CI: 1.88, 4.22) compared
      with normal weight. Stratified analysis showed preconception BMI had a greater
      impact on primiparous women. CONCLUSIONS: Our results support an association
      between self-reported preconception BMI with increased risk of AGT, and it was
      dependent on parity.

PMID- 30100175
TI  - Morphologic variations of the scapula in 3-dimensions: a statistical shape model
      approach.
AB  - BACKGROUND: Morphologic variations of the scapula and acromion have been found to
      be associated with shoulder pathology. This study used statistical shape
      modelling to quantify these variations in healthy shoulders. MATERIALS AND
      METHODS: A statistical shape model of the scapula was created using 3-dimensional
      computed tomography reconstructions of 108 survey-confirmed nonpathologic
      shoulders of 54 patients. The mean shape and the 95% confidence interval were
      calculated and analyzed in the first 5 shape modes. RESULTS: The first 5 shape
      modes consisted of consecutively sized (72% of total variation), rotation of the
      coracoacromial complex (5%), acromial shape and slope (4%), shape of the scapular
      spine (2%), and acromial overhang (2%). DISCUSSION AND CONCLUSION: In healthy
      shoulders, a certain variation in rotation of the coracoacromial complex and in
      acromial shape and slope was observed. These new parameters might be correlated
      with shoulder pathology such as glenohumeral osteoarthritis or rotator cuff
      tears.

PMID- 30100176
TI  - Identifying appropriate candidates for ambulatory outpatient shoulder
      arthroplasty: validation of a patient selection algorithm.
AB  - BACKGROUND: Outpatient total shoulder arthroplasty (TSA) is increasing in
      frequency, but the selection of patients who are appropriate outpatient joint
      candidates remains challenging. We propose an algorithm for selecting outpatient
      TSA candidates, with validation by a cohort of patients from an ambulatory
      surgery center (ASC). METHODS: We identified 61 patients who had primary anatomic
      and reverse TSA. The selection algorithm, which stratifies patients referable to
      their age and cardiopulmonary comorbidities, was used to choose patients for
      outpatient surgery. Complications, including cardiopulmonary, thromboembolic, and
      postoperative wound problems, were recorded. RESULTS: All 61 patients were
      discharged from the ASC on the day of surgery. There were no cardiopulmonary
      events requiring intervention or hospital admission. One patient (2%) required a
      secondary operation, 3 patients (5%) experienced acute surgical complications, 3
      patients (5%) had transient postoperative nausea, and 4 patients (7%) had
      additional complications within the 90-day episode of care. CONCLUSIONS: This
      study is the first to propose a patient selection method for outpatient TSA.
      Using this algorithm for patient selection produced a low rate of perioperative
      complications and no hospital admissions. We suggest this algorithm provides an
      evidence-based method for the standardization of outpatient TSA candidate
      selection.

PMID- 30100177
TI  - Letter to the Editor regarding McLaughlin et al: "Multimodal analgesia decreases
      opioid consumption after shoulder arthroplasty: a prospective cohort study".

PMID- 30100178
TI  - My journey through the elbow.

PMID- 30100179
TI  - Progressive cerebello-cerebral atrophy and progressive encephalopathy with edema,
      hypsarrhythmia and optic atrophy may be allelic syndromes.
AB  - In 2003, a new syndrome was described in the Sephardi Jewish population, named
      progressive cerebello-cerebral atrophy (PCCA) based on the typical
      neuroradiological findings. Following the identification of the causal genes in
      2010 and 2014, two types were defined: PCCA type 1 due to SEPSECS mutations and
      PCCA type 2 due to VPS53 mutations. Progressive encephalopathy with edema,
      hypsarrhythmia and optic atrophy (PEHO) was described in 1991 in Finland. The
      clinical and radiological phenotype resembles PCCA. The genetic background has
      been elusive for many years. Recently, mutations in multiple genes including
      SEPSECS have been described in patients with a PEHO-like syndrome. In 2007 two
      siblings of Moroccan-Jewish origin were diagnosed as having PEHO due to a severe
      developmental encephalopathy, limb and facial edema, intractable epilepsy, optic
      atrophy in one sibling and dysmorphic features. Six years ago an extensive
      workup, including whole exome sequencing, did not reveal the cause. Recently, a
      clinical reevaluation of the siblings suggested the possibility that they suffer
      from PCCA. A reanalysis of the exome data from 2014 revealed that the siblings
      indeed carried the two VPS53 mutations (exon 19 c.2084A>G p.(Gln695Arg) and
      c.1556 + 5G>A) and the parents were found to be carriers. The discovery that
      mutations in both VPS53 and SEPSECS can present with a PEHO-like phenotype, place
      PCCA and PEHO on the same clinical spectrum and suggest they may be allelic
      syndromes.

PMID- 30100180
TI  - Secondary enuresis and urological manifestations in children with ataxia
      telangiectasia.
AB  - BACKGROUND: Ataxia telangiectasia (AT) is a neurodegenerative cerebellar
      disorder, caused by mutations in the ATM gene, involved in DNA repair.
      Radiosensitivity, progressive ataxia, immune deficiency and malignancies, are
      well known symptoms, but urological manifestations are scarcely described.
      OBJECTIVE: To characterize urologic manifestations in a large cohort of AT
      patients. METHODS: Retrospective cross-sectional chart study comprising 52 AT
      patients followed at a National AT Center. RESULTS: 25% of the cohort (13
      patients/8 males) had urologic symptoms, which presented at 11 +/- 4.3 years. The
      most common symptom was secondary enuresis affecting 15% of the patients (8
      children/4 males). Incontinence appeared at 8 +/- 6.2 years of age, and resolved
      spontaneously within 15 +/- 8.3 months in 6 patients. It preceded loss of
      ambulatory capacity by 1-2 years in 7 patients. Lumbosacral MRI were normal (4
      children) and urine cultures (all) were negative. Urodynamic evaluation that was
      performed in only one patient revealed overactive bladder. Additional
      manifestations were macroscopic hematuria due to bladder telangiectasia in a 12
      year-old, and renal cell carcinoma in a 22-year-old. Other manifestations
      unrelated to AT were neprolithiasis, vesico-ureteral reflux and scrotal pain,
      each in 1 patient. DISCUSSION: Transient secondary enuresis is a frequent finding
      in AT patients, heralding loss of ambulatory capacity, tough it's
      pathophysiological mechanism is largely no understood.

PMID- 30100182
TI  - Cooperative Metabolic Adaptations in the Host Can Favor Asymptomatic Infection
      and Select for Attenuated Virulence in an Enteric Pathogen.
AB  - Pathogen virulence exists on a continuum. The strategies that drive symptomatic
      or asymptomatic infections remain largely unknown. We took advantage of the
      concept of lethal dose 50 (LD50) to ask which component of individual non-genetic
      variation between hosts defines whether they survive or succumb to infection.
      Using the enteric pathogen Citrobacter, we found no difference in pathogen
      burdens between healthy and symptomatic populations. Iron metabolism-related
      genes were induced in asymptomatic hosts compared to symptomatic or naive mice.
      Dietary iron conferred complete protection without influencing pathogen burdens,
      even at 1000* the lethal dose of Citrobacter. Dietary iron induced insulin
      resistance, increasing glucose levels in the intestine that were necessary and
      sufficient to suppress pathogen virulence. A short course of dietary iron drove
      the selection of attenuated Citrobacter strains that can transmit and
      asymptomatically colonize naive hosts, demonstrating that environmental factors
      and cooperative metabolic strategies can drive conversion of pathogens toward
      commensalism.

PMID- 30100183
TI  - Pathway of Actin Folding Directed by the Eukaryotic Chaperonin TRiC.
AB  - The hetero-oligomeric chaperonin of eukarya, TRiC, is required to fold the
      cytoskeletal protein actin. The simpler bacterial chaperonin system, GroEL/GroES,
      is unable to mediate actin folding. Here, we use spectroscopic and structural
      techniques to determine how TRiC promotes the conformational progression of actin
      to the native state. We find that actin fails to fold spontaneously even in the
      absence of aggregation but populates a kinetically trapped, conformationally
      dynamic state. Binding of this frustrated intermediate to TRiC specifies an
      extended topology of actin with native-like secondary structure. In contrast,
      GroEL stabilizes bound actin in an unfolded state. ATP binding to TRiC effects an
      asymmetric conformational change in the chaperonin ring. This step induces the
      partial release of actin, priming it for folding upon complete release into the
      chaperonin cavity, mediated by ATP hydrolysis. Our results reveal how the unique
      features of TRiC direct the folding pathway of an obligate eukaryotic substrate.

PMID- 30100181
TI  - Crystal Structure of the COMPASS H3K4 Methyltransferase Catalytic Module.
AB  - The SET1/MLL family of histone methyltransferases is conserved in eukaryotes and
      regulates transcription by catalyzing histone H3K4 mono-, di-, and tri
      methylation. These enzymes form a common five-subunit catalytic core whose
      assembly is critical for their basal and regulated enzymatic activities through
      unknown mechanisms. Here, we present the crystal structure of the intact yeast
      COMPASS histone methyltransferase catalytic module consisting of Swd1, Swd3,
      Bre2, Sdc1, and Set1. The complex is organized by Swd1, whose conserved C
      terminal tail not only nucleates Swd3 and a Bre2-Sdc1 subcomplex, but also joins
      Set1 to construct a regulatory pocket next to the catalytic site. This inter
      subunit pocket is targeted by a previously unrecognized enzyme-modulating motif
      in Swd3 and features a doorstop-style mechanism dictating substrate selectivity
      among SET1/MLL family members. By spatially mapping the functional components of
      COMPASS, our results provide a structural framework for understanding the
      multifaceted functions and regulation of the H3K4 methyltransferase family.

PMID- 30100184
TI  - Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships.
AB  - Synapses are fundamental units of communication in the brain. The prototypical
      synapse-organizing complex neurexin-neuroligin mediates synapse development and
      function and is central to a shared genetic risk pathway in autism and
      schizophrenia. Neurexin's role in synapse development is thought to be mediated
      purely by its protein domains, but we reveal a requirement for a rare glycan
      modification. Mice lacking heparan sulfate (HS) on neurexin-1 show reduced
      survival, as well as structural and functional deficits at central synapses. HS
      directly binds postsynaptic partners neuroligins and LRRTMs, revealing a dual
      binding mode involving intrinsic glycan and protein domains for canonical synapse
      organizing complexes. Neurexin HS chains also bind novel ligands, potentially
      expanding the neurexin interactome to hundreds of HS-binding proteins. Because HS
      structure is heterogeneous, our findings indicate an additional dimension to
      neurexin diversity, provide a molecular basis for fine-tuning synaptic function,
      and open therapeutic directions targeting glycan-binding motifs critical for
      brain development.

PMID- 30100186
TI  - Structure and Conformational Dynamics of a COMPASS Histone H3K4 Methyltransferase
      Complex.
AB  - The methylation of histone 3 lysine 4 (H3K4) is carried out by an evolutionarily
      conserved family of methyltransferases referred to as complex of proteins
      associated with Set1 (COMPASS). The activity of the catalytic SET domain
      (su(var)3-9, enhancer-of-zeste, and trithorax) is endowed through forming a
      complex with a set of core proteins that are widely shared from yeast to humans.
      We obtained cryo-electron microscopy (cryo-EM) maps of the yeast Set1/COMPASS
      core complex at overall 4.0- to 4.4-A resolution, providing insights into its
      structural organization and conformational dynamics. The Cps50 C-terminal tail
      weaves within the complex to provide a central scaffold for assembly. The SET
      domain, snugly positioned at the junction of the Y-shaped complex, is extensively
      contacted by Cps60 (Bre2), Cps50 (Swd1), and Cps30 (Swd3). The mobile SET-I motif
      of the SET domain is engaged by Cps30, explaining its key role in COMPASS
      catalytic activity toward higher H3K4 methylation states.

PMID- 30100185
TI  - Urea Cycle Dysregulation Generates Clinically Relevant Genomic and Biochemical
      Signatures.
AB  - The urea cycle (UC) is the main pathway by which mammals dispose of waste
      nitrogen. We find that specific alterations in the expression of most UC enzymes
      occur in many tumors, leading to a general metabolic hallmark termed "UC
      dysregulation" (UCD). UCD elicits nitrogen diversion toward carbamoyl-phosphate
      synthetase2, aspartate transcarbamylase, and dihydrooratase (CAD) activation and
      enhances pyrimidine synthesis, resulting in detectable changes in nitrogen
      metabolites in both patient tumors and their bio-fluids. The accompanying excess
      of pyrimidine versus purine nucleotides results in a genomic signature consisting
      of transversion mutations at the DNA, RNA, and protein levels. This mutational
      bias is associated with increased numbers of hydrophobic tumor antigens and a
      better response to immune checkpoint inhibitors independent of mutational load.
      Taken together, our findings demonstrate that UCD is a common feature of tumors
      that profoundly affects carcinogenesis, mutagenesis, and immunotherapy response.

PMID- 30100188
TI  - Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood
      Lymphocytes and Tumor Organoids.
AB  - Cancer immunotherapies have shown substantial clinical activity for a subset of
      patients with epithelial cancers. Still, technological platforms to study cancer
      T-cell interactions for individual patients and understand determinants of
      responsiveness are presently lacking. Here, we establish and validate a platform
      to induce and analyze tumor-specific T cell responses to epithelial cancers in a
      personalized manner. We demonstrate that co-cultures of autologous tumor
      organoids and peripheral blood lymphocytes can be used to enrich tumor-reactive T
      cells from peripheral blood of patients with mismatch repair-deficient colorectal
      cancer and non-small-cell lung cancer. Furthermore, we demonstrate that these T
      cells can be used to assess the efficiency of killing of matched tumor organoids.
      This platform provides an unbiased strategy for the isolation of tumor-reactive T
      cells and provides a means by which to assess the sensitivity of tumor cells to T
      cell-mediated attack at the level of the individual patient.

PMID- 30100187
TI  - Nuclear Pores Promote Lethal Prostate Cancer by Increasing POM121-Driven E2F1,
      MYC, and AR Nuclear Import.
AB  - Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport,
      transcription, and genome integrity in eukaryotic cells. However, their
      functional roles in cancer remain poorly understood. We interrogated the
      evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups),
      from primary to advanced metastatic human prostate cancer (PC). Focused loss-of
      function genetic screen of top-upregulated Nups in aggressive PC models
      identified POM121 as a key contributor to PC aggressiveness. Mechanistically,
      POM121 promoted PC progression by enhancing importin-dependent nuclear transport
      of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors,
      uncovering a pharmacologically targetable axis that, when inhibited, decreased
      tumor growth, restored standard therapy efficacy, and improved survival in
      patient-derived pre-clinical models. Our studies molecularly establish a role of
      NPCs in PC progression and give a rationale for NPC-regulated nuclear import
      targeting as a therapeutic strategy for lethal PC. These findings may have
      implications for understanding how NPC deregulation contributes to the
      pathogenesis of other tumor types.

PMID- 30100191
TI  - Multiple abdominal calcified reactive nodular fibrous pseudotumor.

PMID- 30100189
TI  - Reprogramming Yeast Metabolism from Alcoholic Fermentation to Lipogenesis.
AB  - Engineering microorganisms for production of fuels and chemicals often requires
      major re-programming of metabolism to ensure high flux toward the product of
      interest. This is challenging, as millions of years of evolution have resulted in
      establishment of tight regulation of metabolism for optimal growth in the
      organism's natural habitat. Here, we show through metabolic engineering that it
      is possible to alter the metabolism of Saccharomyces cerevisiae from traditional
      ethanol fermentation to a pure lipogenesis metabolism, resulting in high-level
      production of free fatty acids. Through metabolic engineering and process design,
      we altered subcellular metabolic trafficking, fine-tuned NADPH and ATP supply,
      and decreased carbon flux to biomass, enabling production of 33.4 g/L
      extracellular free fatty acids. We further demonstrate that lipogenesis
      metabolism can replace ethanol fermentation by deletion of pyruvate decarboxylase
      enzymes followed by adaptive laboratory evolution. Genome sequencing of evolved
      strains showed that pyruvate kinase mutations were essential for this phenotype.

PMID- 30100190
TI  - [ENT benign lesions and pseudo-tumors: Case No. 3].

PMID- 30100192
TI  - Differences in Code Status and End-of-Life Decision Making in Patients With
      Limited English Proficiency in the Intensive Care Unit.
AB  - OBJECTIVE: To determine whether code status, advance directives, and decisions to
      limit life support were different for patients with limited English proficiency
      (LEP) in the intensive care unit (ICU) as compared with patients whose primary
      language was English. PATIENTS AND METHODS: We conducted a retrospective cohort
      study in adult patients admitted to 7 ICUs in a single tertiary academic medical
      center from May 31, 2011, through June 1, 2014. RESULTS: Of the 27,523 patients
      admitted to the ICU, 779 (2.8%) had LEP. When adjusted for severity of illness,
      sex, education level, and insurance status, patients with LEP were less likely to
      change their code status from full code to do not resuscitate during ICU
      admission (odds ratio [OR], 0.62; 95% CI, 0.46-0.82; P<.001) and took 3.8 days
      (95% CI, 1.9-5.6 days; P<.001) longer to change to do not resuscitate. Patients
      with LEP who died in the ICU were less likely to receive a comfort measures order
      set (OR, 0.38; 95% CI, 0.16-0.91; P=.03) and took 19.1 days (95% CI, 13.2-25.1
      days; P<.001) longer to transition to comfort measures only. Patients with LEP
      were less likely to have an advance directive (OR, 0.23; 95% CI, 0.18-0.29;
      P<.001), more likely to receive mechanical ventilation (OR, 1.26; 95% CI, 1.07
      1.48; P=.005), and more likely to have restraints used (OR, 1.36; 95% CI, 1.11
      1.65; P=.003). The hospital length of stay was 2.7 days longer for patients with
      LEP. Additional adjustment for religion, race, and age yielded similar results.
      CONCLUSION: There are important differences in end-of-life care and decision
      making for patients with LEP.

PMID- 30100193
TI  - Should Procedures or Patients Be Safe? Bias in Recommendations for Periprocedural
      Discontinuation of Anticoagulation.

PMID- 30100194
TI  - Providing postpartum care with limited resources: Experiences of nurse-midwives
      and obstetricians in urban Tanzania.
AB  - BACKGROUND: Tanzania has high maternal and neonatal mortality rates.
      Comprehensive guidelines for postpartum care have been developed by the
      government as a means to improve health outcomes during the perinatal period.
      Despite the creation of these guidelines and the government's commitment to
      universal perinatal care for women and neonates, there is concern that the
      delivery of postpartum services may not be meeting the needs of mothers and
      neonates. AIM: The purpose of this feminist poststructuralist study was to
      explore nurse-midwives' and obstetricians' experiences of providing postpartum
      care in Tanzania. METHODS: This qualitative study used feminist poststructuralism
      to explore the personal, social, and institutional discourses of postpartum care.
      We individually interviewed ten nurse-midwives and three obstetricians in Dar es
      Salaam, Tanzania. Feminist poststructuralist discourse analysis was used to
      analyze the transcribed interviews after their translation from Kiswahili to
      English. FINDINGS: Four main themes were identified. In this paper, we present
      the main theme of availability of resources, and its four corresponding
      subthemes; (1) space, (2) equipment, (3) staffing, and (4) government
      responsibility. DISCUSSION: The findings from our study illustrate the need for
      health workforce planning to be addressed in a comprehensive manner that accounts
      for context, required resources and systemic challenges. These findings are
      consistent with findings from other studies. CONCLUSION: Understanding the
      resource challenges that nurse-midwives and obstetricians are facing in one low
      and-middle-income-country will assist researchers, decision makers, and
      politicians as they address issues of mortality, morbidity, and disrespectful
      maternity care.

PMID- 30100195
TI  - Partner support during the prenatal testing period after assisted conception.
AB  - BACKGROUND: Pregnancy after infertility is a challenging experience. The first
      trimester screening test may add stress. Partner support reduces psychological
      distress in pregnant women after spontaneous conception. No data are available
      for women who conceive via assisted reproductive technology. AIM: To assess
      whether there was a difference between couples who underwent assisted
      reproductive technology and couples who conceived spontaneously in the support
      they felt they provided to their partner and whether their perception of support
      received from their partner reduced their distress. METHODS: This longitudinal
      prospective study included 52 women (spontaneous conception) and 53 women
      (assisted reproductive technology), as well as their partners. Participants
      completed the state scale of the State-Trait Anxiety Inventory, the Edinburgh
      Depression Scale, and two partner-support subscales of the Dyadic Coping
      Inventory: before prenatal testing (gestational age 12 weeks), immediately after
      receiving the results (gestational age of approximately 14 weeks), and once all
      the prenatal screenings had been completed (gestational age 22 weeks). FINDINGS:
      Women who underwent assisted reproductive technology felt less able to help their
      partner cope with stress and felt their partner was less able to help them cope
      with stress than women with spontaneous pregnancy. This difference was not
      observed in men. Higher perceived partner support lowered the anxiety and
      depression of couples who conceived spontaneously, but did not benefit couples
      who followed fertility treatment. CONCLUSION: These results add to our knowledge
      of the emotional state of women and their partners during pregnancy after
      infertility. This knowledge may allow prenatal care providers to offer
      specialized counselling to women and their partners in the transition from
      infertility to parenthood.

PMID- 30100197
TI  - Consumer opinions on adverse events associated with medical devices.
AB  - INTRODUCTION: Post-market surveillance of medical devices relies on compulsory
      and voluntary reports. Although direct consumer reporting of medical device
      related adverse events (AEs) is available in Australia, the proportion of
      consumer reports has remained low. Limited qualitative research has previously
      explored consumer insights on AEs associated with medical devices and in
      particular, AE reporting. OBJECTIVE: To explore consumer opinions on AEs related
      to medical devices, and their knowledge of, experiences with, and views on, the
      reporting of medical device-related AEs. METHODS: Focus groups (n = 4; total of
      29 participants) were conducted in metropolitan Sydney, Australia. Focus group
      discussions of approximately 1.5 h in length centred on consumers' understanding
      of AEs, opinions on AEs and their previous experiences, views on medical device
      benefits and harms, and actions taken (or potential actions) in response to AEs.
      With participant consent, discussions were audio-recorded, transcribed verbatim,
      and thematically analysed. RESULTS: Participants regarded medical device-related
      side effects to be unexpected AEs associated with their use. Where there was a
      clear need for the medical device itself, potential improvement in quality of
      life took precedence over potential harms. Most participants had not experienced
      negative issues with their medical device(s). There was poor awareness among
      participants of an existing direct consumer AE reporting system for medical
      devices. Despite this, the value of reporting was acknowledged. Severity of the
      AE was a key motivator for potential AE reporting. CONCLUSIONS: Further efforts
      are necessary to improve consumer awareness of available AE reporting systems to
      better support post-market surveillance and safe medical device use.

PMID- 30100198
TI  - Clinical decision-making: An essential skill for 21st century pharmacy practice.
AB  - Clinical decision-making skills are recognized as a central component of
      professional competency but are under-developed in pharmacy compared to other
      health professions. There is an urgent need for a comprehensive understanding of
      how pharmacists can best develop and use therapeutic decision-making skills in
      clinical practice. The aims of this commentary are to define clinical decision
      making in pharmacy practice, and to present a model for clinical decision-making
      that aligns with a philosophical framework for pharmacy practice. The model has
      utility in education programs for pharmacists and provides a framework for
      understanding patient-facing clinical services in practice.

PMID- 30100196
TI  - Circulating Adipose Fatty Acid Binding Protein Is a New Link Underlying Obesity
      Associated Breast/Mammary Tumor Development.
AB  - It is clear that obesity increases the risk of many types of cancer, including
      breast cancer. However, the underlying molecular mechanisms by which obesity is
      linked to cancer risk remain to be defined. Herein, we report that circulating
      adipose fatty acid binding protein (A-FABP) promotes obesity-associated breast
      cancer development. Using clinical samples, we demonstrated that circulating A
      FABP levels were significantly increased in obese patients with breast cancer in
      comparison with those without breast cancer. Circulating A-FABP released by
      adipose tissue directly targeted mammary tumor cells, enhancing tumor stemness
      and aggressiveness through activation of the IL-6/STAT3/ALDH1 pathway.
      Importantly, genetic deletion of A-FABP successfully reduced tumor ALHD1
      activation and obesity-associated mammary tumor growth and development in
      different mouse models. Collectively, these data suggest circulating A-FABP as a
      new link between obesity and breast cancer risk, thereby revealing A-FABP as a
      potential new therapeutic target for treatment of obesity-associated cancers.

PMID- 30100199
TI  - Exploring pharmacy service users' support for and willingness to use community
      pharmacist prescribing services.
AB  - BACKGROUND: In 2012, community pharmacists in Ontario, Canada gained regulatory
      authority to independently prescribe, including renew and adapt prescriptions.
      Studies have explored views of pharmacists, physicians and policymakers about
      pharmacist prescribing but less is known about the views of community pharmacy
      services users. OBJECTIVE: To describe Ontario community pharmacy service users'
      support for and stated willingness to use pharmacist prescribing services.
      METHODS: A qualitative descriptive study was conducted with 19 adults who had
      filled or refilled prescription(s) at a community pharmacy within the past three
      months. Participants were recruited through purposive and snowball sampling. Data
      were collected through one-on-one, semi-structured interviews between May and
      September 2016. Interview transcripts were coded and thematic analysis conducted.
      The first two transcripts were independently coded and analyzed by 2 researchers
      and after consensus was achieved, the lead researcher coded and analyzed the
      remainder of the data. RESULTS: Most community pharmacy service users lacked
      experience with pharmacist prescribing services but perceived some potential
      benefits, including personal convenience. The majority of participants supported
      pharmacist prescribing. Support for and stated willingness to use pharmacist
      prescribing services varied by the type of service and was contingent upon the
      clinical purpose of the prescription, pharmacists' access to patient clinical
      information (e.g. health records), and the extent of pharmacist-physician
      collaboration during the prescribing process. CONCLUSION: Community pharmacy
      service users in Ontario expressed varying support for and stated willingness to
      use pharmacist prescribing services. This seemed to be due to their perceptions
      of the pharmacists' role (compared to physicians) and concerns about risks.
      Understanding these contributing factors will help implement strategies that
      address concerns and facilitate use of community pharmacists' prescribing
      services.

PMID- 30100200
TI  - Defining and identifying concepts of medication reconciliation: An international
      pharmacy perspective.
AB  - BACKGROUND: Medication discrepancies occur in up to 80% of hospitalized patients
      during transitions of care, either at admission or discharge. However, numerous
      organization have different definitions of medication reconciliation which may
      result in variations of services being implemented. OBJECTIVE: To develop a
      consensus definition of medication reconciliation and define the essential
      components of medication reconciliation based on international consensus using a
      modified Delphi process. METHODS: Statements and definitions about medication
      reconciliation found in the literature were used to build a Delphi Questionnaire
      and sent to experts around the world. Experts were identified based on their
      leadership in publication, education, professional interest and participation in
      the area of medication management. Delphi rounds continued until an 80% agreement
      was achieved. RESULTS: In total, 24 experts were included in the Delphi panel.
      Three Delphi rounds were required to reach consensus on the key concepts included
      in a medication reconciliation. These concepts included 65 statements classified
      under (1) tasks involved, (2) who can conduct them, (3) when they should be
      conducted, (4) who should receive them, (5) how should it be measured and (6)
      clarifying the difference between medication reconciliation and medication
      review. This led to a proposed definition for medication reconciliation tasks as
      "the process of creating the most accurate list possible of all medications a
      patient is taking and comparing that list against the prescriber's orders. In
      addition, the patient's allergies, history of side effects from medications and
      medication aids are listed with the goal of providing correct medication to the
      patient at all transition points within the health care system." CONCLUSION: An
      international expert panel was able to receive consensus on the definition of
      tasks involved in medication reconciliation and its essential concepts after four
      Delphi rounds. This definition is broader in scope than previous definitions.

PMID- 30100201
TI  - Risk-based Monitoring of Clinical Trials: An Integrative Approach.
AB  - PURPOSE: Clinical trial monitoring is an essential component of drug development
      aimed at safeguarding subject safety, data quality, and protocol compliance by
      focusing sponsor oversight on the most important aspects of study conduct. In
      recent years, regulatory agencies, industry consortia, and nonprofit
      collaborations between industry and regulators, such as TransCelerate and
      International Committee for Harmonization, have been advocating a new, risk-based
      approach to monitoring clinical trials that places increased emphasis on critical
      data and processes and encourages greater use of centralized monitoring. However,
      how best to implement risk-based monitoring (RBM) remains unclear and subject to
      wide variations in tools and methodologies. The nonprescriptive nature of the
      regulatory guidelines, coupled with limitations in software technology,
      challenges in operationalization, and lack of robust evidence of superior
      outcomes, have hindered its widespread adoption. METHODS: We describe a holistic
      solution that combines convenient access to data, advanced analytics, and
      seamless integration with established technology infrastructure to enable
      comprehensive assessment and mitigation of risk at the study, site, and subject
      level. FINDINGS: Using data from completed RBM studies carried out in the last 4
      years, we demonstrate that our implementation of RBM improves the efficiency and
      effectiveness of the clinical oversight process as measured on various quality,
      timeline, and cost dimensions. IMPLICATIONS: These results provide strong
      evidence that our RBM methodology can significantly improve the clinical
      oversight process and do so at a lower cost through more intelligent deployment
      of monitoring resources to the sites that need the most attention.

PMID- 30100202
TI  - Buffy coat-derived platelets cryopreserved using a new method: Results from in
      vitro studies.
AB  - Cryopreservation for the long-term storage of platelets (PLTs) is a useful method
      to overcome the limits of platelet shortage. This is an in vitro prospective
      study to evaluate the count, viability, and function of buffy coat-derived pooled
      platelet concentrates (BC-PLTs), treated with dimethyl sulphoxide (DMSO) and
      cryopreserved (CRY BC-PLTs) at -80  degrees C with a modified Valeri method. PLTs
      were stored in 6% DMSO with a patented kit. Overall, 49 BC-PLTs from 245 healthy
      volunteer donors were prepared, cryopreserved, and analysed before and after 3,
      6, and 9 months of storage. In flow cytometry, a statistically significant
      reduction in CD 42b (92.7 +/- 4.29% at T0 vs. 23.6 +/- 27.5% at T3, 16.38 +/-
      12.54% at T6, and 17.3 +/- 9.6% at T9) and PAC-1 (1.9 +/- 1.34% at T0 vs. 0.62 +/
      0.4% at T3, 0.63 +/- 0.83% at T6, and 0.49 +/- 0.48% at T9) was observed after
      storage. CRY BC-PLTs showed a good and stable endogenous thrombin generation
      potential (nM min): 529.25 +/- 98.64 at T0 vs. 533.04 +/- 103.15 at T9 months.
      CRY BC-PLTs showed a good viability in vitro, according to currently accepted
      criteria for cryopreserved PLTs.

PMID- 30100204
TI  - Health-related quality of life of parotid carcinoma patients-a comparative study
      with parotid adenoma patients and assessment of the influence of demographic,
      treatment, and pathological factors.
AB  - The aim of this study was to compare the health-related quality of life (HRQoL)
      of patients treated for parotid carcinoma (PC) and parotid adenoma (PA). The
      impact of demographic, treatment, and pathological factors was analyzed within
      the PC group. The EORTC QLQ-C30 and QLQ-H&N35 questionnaires were completed by 45
      PC patients and 46 PA patients. A number of HRQoL domains were significantly
      worse in the PC group than in the PA group: global health status, pain, insomnia,
      loss of appetite, mouth opening, swallowing problems, dry mouth, sticky saliva,
      problems with senses and speech, social eating, and cognitive functioning
      (P<0.05). In the PC group, significantly worse scores were found for age
      >55years, radical parotidectomy, neck dissection, radiotherapy, recurrence of the
      disease, pT3/T4 stage, pN+ status, and high-grade tumour (P<0.05). Worse results
      were related to global health status, social contact, mouth opening, weight and
      appetite loss, physical, role, emotional, and social functioning, fatigue, speech
      problems, social eating, and financial difficulties. The study results
      demonstrate worse HRQoL in PC patients in comparison to PA patients. Older age,
      radical parotidectomy, neck dissection, radiotherapy, T3/T4 stage, pN+, high
      grade tumours, and recurrence had a significant influence on HRQoL in PC
      patients.

PMID- 30100205
TI  - Positive regulatory role of c-Src-mediated TRIM25 tyrosine phosphorylation on RIG
      I ubiquitination and RIG-I-mediated antiviral signaling pathway.
AB  - Retinoic acid-inducible gene I (RIG-I) detects viral RNAs and induces antiviral
      responses. During viral RNA recognition by RIG-I, tripartite motif protein 25
      (TRIM25) plays a critical regulatory role by inducing K63-linked RIG-I
      polyubiquitination. Previous proteomics analysis revealed several phosphorylation
      sites on TRIM25, including tyrosine 278 (Y278), yet the roles of these
      modifications remain elusive. Here, we demonstrated that TRIM25 interacted with c
      Src and underwent tyrosine phosphorylation by c-Src kinase upon viral infection
      and the phosphorylation is required for the complete activation of RIG-I
      signaling. Analysis using a c-Src inhibitor and TRIM25 mutant, in which tyrosine
      278 is substituted by phenylalanine (Y278F), suggested that the phosphorylation
      positively regulates K63-linked polyubiquitination of RIG-I and subsequent
      antiviral signaling. The TRIM25 Y278F mutant displayed decreased E3-ubiquitin
      ligase activity in vitro, suggesting that this phosphorylation event affects the
      E3-ligase activity of TRIM25. Thus, we provide a molecular mechanism of c-Src
      mediated positive regulation of RIG-I signaling.

PMID- 30100203
TI  - The Estimates of the Health and Economic Burden of Dengue in Vietnam.
AB  - Dengue has been estimated to cause a substantial health and economic burden in
      Vietnam. The most recent studies have estimated that it is responsible for 39884
      disability-adjusted life years (DALYs) annually, representing an economic burden
      of US$94.87 million per year (in 2016 prices). However, there are alternative
      burden estimates that are notably lower. This variation is predominantly due to
      differences in how the number of symptomatic dengue cases is estimated.
      Understanding the methodology of these burden calculations is vital when
      interpreting health economic analyses of dengue. This review aims to provide an
      overview of the health and economic burden estimates of dengue in Vietnam. We
      also highlight important research gaps for future studies.

PMID- 30100206
TI  - The 6-Minute Walk Test as a Tool for Determining Exercise Capacity and Prognosis
      in Patients with Silicosis.
AB  - OBJECTIVE: To evaluate exercise capacity using the 6-minute walk test (6MWT) in
      patients with complicated silicosis, and to determine how results shape the
      prognostic value of 6MWT for hospitalization and mortality. METHOD: Prospective
      observational study in 143 patients with complicated silicosis who performed the
      6MWT in our outpatient pulmonology clinic between 2009 and the end of 2016. Lung
      function tests, computed tomography findings and 6MWT parameters (distance walked
      and oxygen desaturation) were evaluated. RESULTS: Patients with complicated
      silicosis walked 387+/-92m. Results deteriorated as silicosis severity increased;
      category A: 407+/-97m, B: 370+/-88m, and C: 357+/-68m (P=.022). The 6MWT
      correlated positively with lung function and inversely with dyspnea determined by
      mMRC (P<.001). Patients with moderate/severe emphysema and greater CT90 presented
      a worse result on 6MWT. Patients who walked<350m had more hospitalizations (3.7+/
      4.0) than those who walked>350m (1.1+/-2.9). There was an impact on survival: non
      survivors walked 327.9+/-73.0m, while survivors walked 404.5+/-89.7m (P<.001).
      CONCLUSIONS: Spirometry values and category of complicated silicosis correlated
      with 6MWT and distance walked was a prognostic factor for hospitalization and
      mortality. The 6MWT is a useful tool in occupational health for monitoring
      patients with silicosis.

PMID- 30100207
TI  - Prognostic Factors for Thrombosis in Cancer Patients.

PMID- 30100208
TI  - A rare cause of systemic inflammatory response syndrome.

PMID- 30100210
TI  - MicroRNA regulation of natural killer cell development and function in leukemia.
AB  - MicroRNAs (miRNAs) are now recognized as important regulators of all cellular
      processes, including immune function and cancer survival. These evolutionary
      preserved, single-stranded, non-coding RNA molecules mediate important functional
      effects primarily through post-transcriptional regulation of protein expression.
      MiRNAs are known to mediate multiple oncogenic pathways in tumor cells, both
      tumor promoting and tumor suppressing. In addition to a direct tumor cell effect,
      miRNAs have also been shown to play a critical role in immune cell development,
      function and survival. Here we expand on previous reports to evaluate miRNA
      regulation in natural killer (NK) cells primarily in humans and focus on their
      influence on NK cell development and function in the setting of hematologic
      malignancies. In addition, we highlight the most recent miRNA discoveries in
      hematologic malignancies and discuss areas of future exploration relevant to the
      translational field of innate immunology and miRNA-based therapeutic
      intervention.

PMID- 30100209
TI  - Concurrent use of ketamine and monoamine oxidase inhibitors in the treatment of
      depression: A letter to the editor.

PMID- 30100211
TI  - Proteomics analysis of site- and stage-specific protein expression after
      peripheral nerve injury.
AB  - BACKGROUND: The peripheral nervous system has greater regenerative potential than
      the CNS. This fact suggests the existence of molecules that act as key factors in
      nerve regeneration during molecular changes in the peripheral nervous system.
      METHODS: The right sciatic nerve of female Sprague-Dawley rats was exposed and
      transected at the mid-thigh level. Animals were sacrificed at 5, 10 or 35 days
      after nerve transection. Proximal and distal nerve segments (1-cm in length) were
      dissected. We then sought to observe overall molecular changes after peripheral
      nerve injury using a proteomic approach. For an overview of the identified
      proteins, each protein was classified according to its biological and molecular
      functions. We identified a number of proteins showing site- and stage-specific
      patterns of expression. RESULTS: Both proximal and distal molecular changes at 5,
      10 and 35 days after nerve transection were investigated, and a total of 2353
      proteins were identified. Among the various expression patterns observed, aFGF
      and GAP-43 were found to increase in the proximal stump at 10 days after
      transection, and PN-1, RPL9 and prosaposin increased in the distal stump at 5
      days after transection. Among these proteins, aFGF, GAP-43, PN-1 and prosaposin
      were found to be associated with nerve regeneration. CONCLUSION: We demonstrated
      that aFGF, GAP-43, PN-1 and prosaposin expression increased at specific stages
      and in specific sites, such as the proximal or distal stump, after nerve
      transection by comprehensive measurement using proteomics analysis. We believe
      that these specific expression patterns might play important roles during
      regeneration after nerve injury.

PMID- 30100212
TI  - Joint distraction and early mobilization using a new dynamic external finger
      fixator for the treatment of fracture-dislocations of the proximal
      interphalangeal joint.
AB  - BACKGROUND: Dynamic external fixation is a useful treatment option for unstable
      fracture-dislocations of the proximal interphalangeal (PIP) joint, because it
      simultaneously reduces axial pressure load on the joint surface, maintains
      congruent joint reduction, and permits early joint motion. However, most current
      devices are large, hindering finger movement, and unstable. To address these
      problems, we developed a dynamic external finger fixator, named the Micro Ortho
      Fixator(r). The purpose of this study was to review the results of using the new
      external finger fixator to treat unstable fracture-dislocations of the PIP joint.
      MATERIALS AND METHODS: Nine patients who sustained unstable fracture-dislocation
      injuries of the PIP joint were treated with the Micro Ortho Fixator(r). Seven
      fractures were accompanied by depressed bony fragments at the base of the middle
      phalanx. All patients were evaluated for pain and range of PIP motion at the
      final follow-up. Radiographs of the affected fingers were evaluated for PIP
      congruity and reduction. The mean follow-up duration was 11.1 months (range: 6-33
      months). RESULTS: At the final follow-up, pain averaged 0.3 (range: 0-2) on the
      Numeric Pain Rating Scale, and the total arc of motion at the PIP joint averaged
      91.2 degrees  (range: 50-110 degrees ). All fractures had healed, and the intra
      articular step-off improved from 1.9 mm (SD: 1.0) before surgery to 0.2 mm (SD:
      0.4) at the final follow-up. The patients who sustained sports injuries returned
      to competition after an average of 3.5 months (range: 2.5-4 months). CONCLUSION:
      The external fixator is compact and facilitates range-of-motion (ROM) exercises,
      has high stability, and achieves good joint congruity and an ROM equivalent to
      the healthy joint of the patient. STUDY DESIGN/LEVEL OF EVIDENCE: Therapeutic/IV.

PMID- 30100213
TI  - Diameter Criteria Have Limited Value for Prediction of Functional Dialysis Use of
      Arteriovenous Fistulas.
AB  - OBJECTIVE: To determine the value of diameter measurements for prediction of
      functional dialysis use (FDU) of arteriovenous fistulas (AVF). METHODS: Review of
      access operations and dialysis databases from January 1, 2007 to August 1, 2015.
      Follow up until July 1, 2016. FDU defined as six consecutive dialysis sessions
      with two needles on the AVF. Artery and vein diameters measured by portable
      ultrasound in access clinic. Contribution of diameter to predict FDU assessed
      with logistic regression. Diagnostic accuracy assessed by sensitivity,
      specificity, positive and negative predictive values (PPV and NPV). RESULTS: 803
      AVF operations were analysed: 507 (63%) radiocephalic fistulas (RCAVF), 237 (30%)
      brachiocephalic fistulas (BCAVF), and 59 (7%) brachiobasilic fistulas (BBAVF).
      Women had lower FDU in RCAVF (0.65, 95% CI 0.58-0.72 vs. 0.86, 95% CI 0.81-0.89;
      p < .0001), but not in BCAVF (0.83, 95% CI 0.75-0.89 vs. 0.81, 95% CI 0.73-0.88;
      p = .75). Female gender was an independent negative predictor of FDU in RCAVF (OR
      0.31; 95% CI 0.20-0.49). Vascular kidney disease was an independent negative
      predictor for FDU in RCAVF (OR 0.33; 95% CI 0.17-0.64) and BCAVF (OR 0.22; 95% CI
      0.09-0.57) in multivariable analysis. Artery and vein diameter did not improve
      the model for RCAVF. Vein diameter as categorical variable improved the model for
      BCAVF. Diameter cut off of radial artery >= 2 mm has 96% sensitivity, 86% PPV, 9%
      specificity, and 29% NPV in men. Radial artery diameter >=2 mm had 96%
      sensitivity, 67% PPV but 13% specificity and 62% NPV in women. CONCLUSIONS:
      Diameter is a poor predictor of FDU of AVF. Arterial diameter measurements add no
      diagnostic value for BCAVF. Poor specificity suggests a diameter under 2 mm at
      the wrist should not preclude AVF formation. Vascular kidney disease is an
      independent negative predictor for FDU in all AVF.

PMID- 30100214
TI  - Park-based physical activity interventions for persons with disabilities: A mixed
      methods systematic review.
AB  - BACKGROUND: Park-based physical activity (PA) interventions improve health in the
      general population, but it is unknown if the evidence can be translated to
      persons with disabilities. OBJECTIVES: To conduct a mixed-methods systematic
      synthesis of the evidence for park-based physical activity interventions for
      persons with disabilities and secondarily, to consider the health benefits across
      the lifespan (children and adolescents, young, middle, and older adults).
      METHODS: All major electronic databases were searched from inception until 30th
      November 2016. Studies were eligible if the PA intervention was conducted in an
      urban park environment with people reporting a disability (e.g. physical,
      psychological and developmental impairments) and health outcomes were evaluated
      with biopsychosocial measures. Methodological quality was assessed using Crowes
      Critical Appraisal Tool (CCAT) and key findings extracted. RESULTS: Six
      quantitative and four qualitative papers, comprising of 446 participants (age
      range seven to ninety-one years), were included for qualitative synthesis; five
      in children/adolescents, none in adults, and five in older adults. There was
      limited, low level, preliminary evidence for short-term improvements in physical,
      psychological, and social health outcomes in children and older adults with
      disabilities as well as improvements in disability-related impairments. When
      accessible, parks fostered societal inclusion. CONCLUSIONS: Health benefits from
      park use in persons with disabilities were identified. Parks may provide an
      alternative environment for rehabilitation and management of disabilities.
      Further randomized controlled trials evaluating the long-term effectiveness of
      park-based interventions is necessary to corroborate our findings. Legislative
      commitment ensuring urban parks are accessible may mitigate some health
      disparities in persons with disabilities.

PMID- 30100215
TI  - Mortality after pulmonary embolism in patients with diabetes. Findings from the
      RIETE registry.
AB  - BACKGROUND: Among patients presenting with pulmonary embolism (PE), those with
      diabetes are at increased risk to die than those without diabetes. The reasons
      have not been identified. We used the RIETE (Registro Informatizado Enfermedad
      Trombo Embolica) database to compare the mortality rate and the causes of death
      during anticoagulation in patients with PE according to the presence or absence
      of diabetes. METHODS: A matched retrospective cohort study from consecutively
      enrolled patients in RIETE, from 179 hospitals in 24 countries. For each patient
      with diabetes we selected two patients with no diabetes matched by age, sex and
      year of diagnosis of the PE. RESULTS: As of September 2017, there were 2010 PE
      patients with diabetes and two age-and-gender matched controls. Mean age was 74
      +/- 11 years, 46% were men. Patients with diabetes were more likely to have co
      morbidities, to be using antiplatelets and to have more severe PE. During
      anticoagulation (median, 219 days), patients with diabetes had a higher mortality
      (hazard ratio [HR]: 1.45; 95% confidence intervals [CI]: 1.25-1.67) and a higher
      rate of arterial ischemic events (HR: 2.89; 95%CI: 1.71-4.94) than those without
      diabetes. On multivariable analysis, diabetes was not associated with an
      increased risk for death (HR: 1.26; 95%CI: 0.97-1.63). We also failed to find
      differences according to the use of antiplatelet drugs concomitantly.
      CONCLUSIONS: In our cohort of patients with PE, diabetes was not an independent
      predictor for death. The influence of arterial events or antiplatelet drugs (if
      any) was low.

PMID- 30100216
TI  - Lymphocytic variant hypereosinophilia: a challenging diagnosis of a rare disease
      with pleomorphic clinical picture.

PMID- 30100217
TI  - National trends in diabetes mellitus hospitalization in Spain 1997-2010: Analysis
      of over 5.4 millions of admissions.
AB  - AIMS: To analyze national trends in the rates of hospitalizations (all-cause and
      by principal discharge diagnosis) in total diabetic population of Spain. METHODS:
      We carried out a nation-wide population-based study of all diabetic patients
      hospitalized between 1997 and 2010. All-cause hospitalizations, hospitalizations
      by principal discharge diagnosis, mean age, Charlson Comorbidity Index,
      readmission rates and length of hospital stay were examined. Annual rates
      adjusted for age and sex were analyzed and trends were calculated. RESULTS: Over
      14-years-period, all-cause hospitalizations of diabetic patients increased
      significantly, with an average annual percentage change of 2.5 (95%CI: 1.5-3.5;
      Ptrend < 0.01). The greatest increase was observed in heart failure (5.4; 95%CI:
      4.8-6.0; Ptrend < 0.001), followed by neoplasms (4.9; 95%CI: 3.6-5.8; Ptrend <
      0.001), pneumonia (2.7; 95%CI: 2.0-4.0; Ptrend < 0.001), stroke (2.4; 95%CI: 1.6
      3.4; Ptrend < 0.001), chronic obstructive pulmonary disease (2.0; 95%CI: 1.4-3.4;
      Ptrend < 0.001) and coronary artery disease (1.6; 95%CI: 1.1-2.3; Ptrend < 0.01).
      The adjusted number of all-cause hospitalizations of patients with diabetes per
      100,000 inhabitants increased 2.6-fold. The increase in hospitalizations was
      significantly higher among patients >=75 years old. Males experienced a greater
      increase in all-cause, neoplasm, heart failure, chronic obstructive pulmonary
      disease, and pneumonia hospitalizations (p < 0.01 for all). Hospitalized diabetic
      patients were progressively older and had more comorbidities, higher readmission
      rates and shorter hospital stays (p < 0.05 for all). CONCLUSIONS:
      Hospitalizations of diabetic patients more than doubled in Spain during the study
      period. Heart failure and neoplasms experienced the greatest annual increases and
      remained the principal causes of hospitalization, probably associated with
      advanced age and comorbidities of hospitalized diabetics. Coronary and
      cerebrovascular diseases experienced a lower annual increase, suggesting an
      improvement in cardiovascular care in diabetes in Spain.

PMID- 30100219
TI  - The shape and mobility of the thoracic spine in asymptomatic adults - A
      systematic review of in vivo studies.
AB  - A comprehensive knowledge of the thoracic shape and kinematics is essential for
      effective risk prevention, diagnose and proper management of thoracic disorders
      and assessment of treatment or rehabilitation strategies as well as for in silico
      and in vitro models for realistic applications of boundary conditions. After an
      extensive search of the existing literature, this study summarizes 45 studies on
      in vivo thoracic kyphosis and kinematics and creates a systematic and detailed
      database. The thoracic kyphosis over T1-12 determined using non-radiological
      devices (34 degrees ) was relatively less than measured using radiological
      devices (40 degrees ) during standing. The majority of kinematical measurements
      are based on non-radiological devices. The thoracic range of motion (RoM) was
      greatest during axial rotation (40 degrees ), followed by lateral bending (26
      degrees ), and flexion (21 degrees ) when determined using non-radiological
      devices during standing. The smallest RoM was identified during extension (13
      degrees ). The lower thoracic level (T8-12) contributed more to the RoM than the
      upper (T1-4) and middle (T4-8) levels during flexion and lateral bending. During
      axial rotation and extension, the middle level (T4-8) contributed the most.
      Coupled motion was evident, mostly during lateral bending and axial rotation.
      With aging, the thoracic kyphosis increased by about 3 degrees  per decade,
      whereas the RoM decreased by about 5 degrees  per decade for all load directions.
      These changes with aging mainly occurred in the lower region (T6-12). The
      influence of sex on thoracic kyphosis and the RoM has been described as partly
      contradictory. Obesity was found to decrease the thoracic RoM. Studies comparing
      standing, sitting and lying reported the effect of posture as significant.

PMID- 30100218
TI  - Cellular homeostatic tension and force transmission measured in human engineered
      tendon.
AB  - Tendons transmit contractile muscular force to bone to produce movement, and it
      is believed cells can generate endogenous forces on the extracellular matrix to
      maintain tissue homeostasis. However, little is known about the direct mechanical
      measurement of cell-matrix interaction in cell-generated human tendon constructs.
      In this study we examined if cell-generated force could be detected and
      quantified in engineered human tendon constructs, and if glycosaminoglycans
      (GAGs) contribute to tendon force transmission. Following de-tensioning of the
      tendon constructs it was possible to quantify an endogenous re-tensioning.
      Further, it was demonstrated that the endogenous re-tensioning response was
      markedly blunted after interference with the cytoskeleton (inhibiting non-muscle
      myosin-dependent cell contraction by blebbistatin), which confirmed that re
      tensioning was cell generated. When the constructs were elongated and held at a
      constant length a stress relaxation response was quantified, and removing 27% of
      the GAG content of tendon did not alter the relaxation behavior, which indicates
      that GAGs do not play a meaningful role in force transmission within this system.

PMID- 30100220
TI  - Lower Trabecular Bone Score is Associated With the Use of Proton Pump Inhibitors.
AB  - INTRODUCTION: Trabecular bone score (TBS) provides indirect indices of trabecular
      microarchitecture and bone quality. Several studies have evaluated the influence
      of proton pump inhibitors (PPIs) on bone mass and geometric parameters, but no
      studies have evaluated the influence of PPIs on TBS. METHODS: We reviewed the
      medical records of 1505 women aged 40-89 yr who had bone mineral density (BMD)
      examinations as a part of the medical diagnosis and disease prevention program
      and who did not have osteoporotic fractures or conditions that could affect bone
      metabolism. Among these, we identified 223 women with exposure to PPIs and
      selected the same number of age- and body mass index (BMI)-matched control
      patients. We compared TBS and BMD between the PPI exposure group and the control
      group and performed multivariate regression analyses to determine whether TBS and
      BMDs are associated with age, BMI, and PPIs exposure. We also examined whether
      TBS and BMDs are associated with PPIs exposure timing (current, recent, and
      past). RESULTS: TBS and BMDs were significantly lower in the PPI exposure group
      than in the control group. In a multivariable linear regression analysis, TBS was
      significantly associated with age (p < 0.001) and PPI exposure (p = 0.02). In
      addition, all BMDs were found to be significantly associated with age, BMI, and
      PPI exposure. Lower TBS was associated with current PPIs use (p = 0.005), but not
      with recent or past PPIs usage. However, the influence of PPI exposure timing on
      the BMDs was not consistent between BMD measurement sites. CONCLUSIONS: This
      study found that TBS is lower in subjects with PPIs exposure than in controls.
      The association of lower TBS with current PPIs use suggests that trabecular bone
      quality could be affected early by PPIs, and but the effect might be reversible.

PMID- 30100221
TI  - Emerging Aspects of the Body Composition, Bone Marrow Adipose Tissue and Skeletal
      Phenotypes in Type 1 Diabetes Mellitus.
AB  - Anthropomorphic measures among type 1 diabetic patients are changing as the
      obesity epidemic continues. Excess fat mass may impact bone density and
      ultimately fracture risk. We studied the interaction between bone and adipose
      tissue in type 1 diabetes subjects submitted to two different clinical
      managements: (I) conventional insulin therapy or (II) autologous nonmyeloablative
      hematopoietic stem-cell transplantation (AHST). The study comprised 3 groups
      matched by age, gender, height and weight: control (C = 24), type 1 diabetes (T1D
      = 23) and type 1 diabetes treated with AHST (T1D-AHST = 9). Bone mineral density
      (BMD) and trabecular bone score (TBS) were assessed by dual X-ray absorptiometry
      (DXA). 1H Magnetic resonance spectroscopy was used to assess bone marrow adipose
      tissue (BMAT) in the L3 vertebra, and abdominal magnetic resonance imaging was
      used to assess intrahepatic lipids (IHL), visceral (VAT) and subcutaneous adipose
      tissue (SAT). Individuals conventionally treated for T1D were more likely to be
      overweight (C = 23.8 +/- 3.7; T1D = 25.3 +/- 3.4; T1D-AHST = 22.5 +/- 2.2 Kg/m2;
      p > 0.05), but there was no excessive lipid accumulation in VAT or liver. Areal
      BMD of the three groups were similar at all sites; lumbar spine TBS (L3) was
      lower in type 1 diabetes (p < 0.05). Neither SAT nor VAT had any association with
      bone parameters. Bone marrow adipose tissue (BMAT) lipid profiles were similar
      among groups. BMAT saturated lipids were associated with cholesterol, whereas
      unsaturated lipids had an association with IGF1. Overweight and normal weight
      subjects with type 1 diabetes have normal areal bone density, but lower
      trabecular bone scores. Adipose distribution is normal and BMAT volume is similar
      to controls, irrespective of clinical treatment.

PMID- 30100222
TI  - Admission heart rate and in-hospital course of patients with Takotsubo syndrome.
AB  - BACKGROUND: In-hospital course of patients with Takotsubo syndrome (TS) is quite
      heterogeneous and life-threatening complications are not uncommon in the acute
      phase. The role of heart rate (HR) as a predictor of prognosis has not been
      sufficiently investigated in this setting. The study aims to assess the impact of
      HR at presentation on in-hospital course of patients with TS. METHODS: The study
      population included 221 patients with TS enrolled in a multicentric registry. HR
      at admission was evaluated on the first electrocardiogram. According to tertile
      distribution of HR at presentation, 3 groups were identified: Group A (HR <= 76
      beats per minute (bpm), n = 76), Group B (HR 77-95 bpm, n = 74) and Group C (HR >
      95 bpm, n = 71). Acute in-hospital complications were defined as occurrence of
      severe pump failure and major arrhythmias. RESULTS: 32 (14.4%) patients
      experienced complicated in-hospital course. HR on admission was significantly
      higher (108 bpm vs. 85 bpm; p < 0.001) and ejection fraction (EF) lower (35% vs.
      40%; p = 0.009) in patients with complications than in those without. Patients in
      Group C experienced a 5-fold higher rate of complications compared to group A and
      B. After multivariate analysis, higher HR (odds ratio 1.34 per 10 bpm increase,
      95% confidence interval (CI) 1.12-1.59; p = 0.001) and lower EF (odds ratio 1.24
      per 5% decrease, 95% CI 1.01-1.54; p = 0.049) remained independently associated
      with a worse outcome. CONCLUSION: In a large population with TS, high HR on
      admission independently predicted complicated in-hospital course.

PMID- 30100223
TI  - A potential and novel therapeutic approach to ischemic heart failure: Algisyl
      LVR.

PMID- 30100224
TI  - Prediction of myocardial infarction, stroke and cardiovascular mortality with
      urinary biomarkers of oxidative stress: Results from a large cohort study.
AB  - BACKGROUND: Oxidative stress contributes to endothelial dysfunction and is
      involved in the pathogenesis of cardiovascular diseases (CVD). However, large
      population-based cohort studies are sparse and biomarkers of oxidative stress
      have not been evaluated for CVD risk prediction so far. METHODS: The associations
      of urinary oxidized guanine/guanosine (OxGua) levels (including 8-hydroxy-2'
      deoxyguanosine (8-OHdGuo)) and 8-isoprostane levels with myocardial infarction,
      stroke and CVD mortality were examined in a population-based cohort of 9949 older
      adults from Germany with 14 years of follow-up in multivariable adjusted Cox
      proportional hazards models. RESULTS: Both OxGua and 8-isoprostane levels were
      associated with CVD mortality independently from other risk factors (hazard ratio
      (HR) [95% confidence interval] of top vs. bottom tertile: 1.32 [1.06; 1.64] and
      1.58 [1.27; 1.98], respectively). Moreover, CVD mortality risk prediction was
      significantly improved when adding the two biomarkers to the European Society of
      Cardiology's Systematic Coronary Risk Evaluation (ESC SCORE) tool. The area under
      the curve (AUC) increased from 0.739 to 0.752 (p = 0.001). In addition, OxGua
      levels were associated with stroke incidence (HR for 1 standard deviation
      increase: 1.07 [1.01; 1.13]) and 8-isoprostane levels were associated with fatal
      stroke incidence (HR of top vs. bottom tertile: 1.77 [1.09; 2.89]). With respect
      to myocardial infarction, associations were observed for both biomarkers in obese
      subjects (BMI >= 30 kg/m2). CONCLUSIONS: These results from a large cohort study
      add evidence to the involvement of an imbalanced redox system to the etiology of
      CVD. In addition, 8-isoprostane and OxGua measurements were shown to be useful
      for an improved CVD mortality prediction.

PMID- 30100225
TI  - Cardiovascular risk factors in adults with congenital heart defects - Recognised
      but not treated? An analysis of the German National Register for Congenital Heart
      Defects.
AB  - BACKGROUND: As adult congenital heart disease (ACHD) patients are aging, a high
      prevalence of cardiovascular risk factors is encountered similar to the general
      population. Currently, data regarding the primary and secondary prevention of
      acquired cardiovascular disease in ACHD is lacking. METHODS: The German National
      Register of Congenital Heart Defects was systematically screened for ACHD
      patients with established cardiovascular risk factors or documented acquired
      cardiovascular conditions. Data were analyzed with regard to the according
      medical treatment. RESULTS: Overall, 539 patients were included (mean age 38.4 +/
      17.7 years, 49.2% female). Diabetes was present in 57 pts. (10.6%), arterial
      hypertension in 113 pts. (21.0%), hyperlipidaemia in 81 pts. (15.0%) and obesity
      in 271 pts. (50.2%). 31 pts. (5.8%) were smokers. Coronary artery disease was
      established in 16 pts. (3.0%), peripheral vascular disease in 9 pts. (1.7%), and
      cerebrovascular accidents in 141 pts. (26.2%). Out of the patients with coronary
      artery disease only 81.3% received antithrombotic treatment. Only 18.8% were
      prescribed a statin. Of the pts. with peripheral arterial disease, 44.4% received
      an antiplatelet drug, and only 22.2% were on a statin. Patients with arterial
      hypertension received antihypertensive drugs in 66.4%. CONCLUSIONS: Primary and
      secondary prevention of acquired cardiovascular disease in ACHD is underutilized.
      This highlights the importance of educating primary physicians as well as ACHD
      physicians about the need of primary and secondary prevention for acquired
      cardiovascular disease.

PMID- 30100226
TI  - Cannabidiol improves frequency and severity of seizures and reduces adverse
      events in an open-label add-on prospective study.
AB  - The objective of this study was to characterize the changes in adverse events,
      seizure severity, and frequency in response to a pharmaceutical formulation of
      highly purified cannabidiol (CBD; Epidiolex(r)) in a large, prospective, single
      center, open-label study. We initiated CBD in 72 children and 60 adults with
      treatment-resistant epilepsy (TRE) at 5 mg/kg/day and titrated it up to a maximum
      dosage of 50 mg/kg/day. At each visit, we monitored treatment adverse events with
      the adverse events profile (AEP), seizure severity using the Chalfont Seizure
      Severity Scale (CSSS), and seizure frequency (SF) using seizure calendars. We
      analyzed data for the enrollment and visits at 12, 24, and 48 weeks. We recorded
      AEP, CSSS, and SF at each follow-up visit for the weeks preceding the visit
      (seizures were averaged over 2-week periods). Of the 139 study participants in
      this ongoing study, at the time of analysis, 132 had 12-week, 88 had 24-week, and
      61 had 48-week data. Study retention was 77% at one year. There were no
      significant differences between participants who contributed all 4 data points
      and those who contributed 2 or 3 data points in baseline demographic and
      AEP/SF/CSSS measures. For all participants, AEP decreased between CBD initiation
      and the 12-week visit (40.8 vs. 33.2; p < 0.0001) with stable AEP scores
      thereafter (all p >= 0.14). Chalfont Seizure Severity Scale scores were 80.7 at
      baseline, decreasing to 39.2 at 12 weeks (p < 0.0001) and stable CSSS thereafter
      (all p >= 0.19). Bi-weekly SF decreased from a mean of 144.4 at entry to 52.2 at
      12 weeks (p = 0.01) and remained stable thereafter (all p >= 0.65). Analyses of
      the pediatric and adult subgroups revealed similar patterns. Most patients were
      treated with dosages of CBD between 20 and 30 mg/kg/day. For the first time, this
      prospective, open-label safety study of CBD in TRE provides evidence for
      significant improvements in AEP, CSSS, and SF at 12 weeks that are sustained over
      the 48-week duration of treatment.

PMID- 30100227
TI  - Identification of a novel PAFAH1B1 missense mutation as a cause of mild
      lissencephaly with basal ganglia calcification.
AB  - PURPOSE: To investigate the genetic and clinical features of a Chinese family
      exhibiting an autosomal dominant inheritance pattern of lissencephaly. METHODS:
      Clinical examinations and cranial imaging studies were performed for all members
      of the family (two unaffected members and three surviving members from a total of
      four affected members). In addition, whole-exome sequencing analysis was
      performed for DNA from an affected patient to scan for candidate mutations,
      followed by Sanger sequencing to verify these candidate mutations in the entire
      family. A total of 200 ethnicity-matched healthy controls without
      neuropsychiatric disorder were also included and analyzed. RESULTS: We identified
      a novel missense mutation, c.412G > A, p.(E138K), that cosegregated with the
      disease in exon 6 of the platelet activating factor acetylhydrolase 1b regulatory
      subunit 1 (PAFAH1B1) gene in the affected members; this mutation was not found in
      the 200 controls. Multiple sequence alignments showed that codon 138, where the
      mutation (c.G412A) occurred, was located within a phylogenetically conserved
      region. Brain magnetic resonance imaging revealed calcification within the
      bilateral globus pallidus in all three affected members. CONCLUSIONS: We
      identified a novel missense mutation, c.412G > A, p.(E138K),in the PAFAH1B1 gene
      of a Chinese family with lissencephaly. In addition, our findings suggest that
      basal ganglia calcification is a novel clinical feature of PAFAH1B1-related
      lissencephaly.

PMID- 30100228
TI  - Current Situation of the Treatment of Arrhythmias in Children in Spain. Finding a
      Place of its Own.

PMID- 30100229
TI  - CRISPR in Sub-Saharan Africa: Applications and Education.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPR) technology has
      enabled genetic engineering feats previously considered impracticable, offering
      great hopes for solutions to problems facing society. We consider it timely to
      highlight how CRISPR can benefit public health, medicine, and agriculture in sub
      Saharan Africa (SSA) and offer recommendations for successful implementation.

PMID- 30100230
TI  - The silent course of liver steatosis and fibrosis in an adult patient with
      Cholesteryl Ester Storage Disease.

PMID- 30100231
TI  - Primary sclerosing cholangitis response to the combination of fibrates with
      ursodeoxycholic acid: French-Spanish experience.
AB  - BACKGROUND & AIMS: In patients with primary sclerosing cholangitis (PSC),
      ursodeoxycholic acid (UDCA) treatment improves serum liver tests and surrogate
      markers of prognosis but has no proven effect on survival. Additional therapies
      are obviously needed. Fibrates, PPAR agonists with anti-cholestatic properties,
      have a beneficial effect in primary biliary cholangitis. The aim of this study
      was to evaluate the safety and efficacy of fibrates in PSC patients. METHODS:
      Retrospectively, we investigated PSC patients treated with fibrates (fenofibrate
      200mg/day or bezafibrate 400mg/day) for at least 6 months in addition to UDCA,
      after an incomplete biochemical response (alkaline phosphatase [ALP] >=1.5*upper
      limit of normal) to UDCA. Changes in biochemical parameters and clinical features
      were assessed. RESULTS: Twenty patients were included (fourteen from Paris and
      six from Barcelona): median age 43.8 years, median liver stiffness 11kPa (>=F3).
      Upon treatment with fibrates (median duration of 1.56 years), liver tests
      significantly improved, including a reduction of ALP levels by 41% and pruritus
      significantly decreased. No serious adverse event attributable to fibrates
      occurred. Discontinuation of fibrates was followed by a clear rebound of ALP.
      Despite biochemical improvement, liver stiffness significantly increased.
      CONCLUSIONS: Combining UDCA with fibrates results in a significant biochemical
      improvement and pruritus decrease in PSC patients with incomplete response to
      UDCA. These results provide a rationale for larger and prospectively designed
      studies to establish the efficacy and safety of fibrates in PSC.

PMID- 30100232
TI  - Excessive Screen Time and Psychosocial Well-Being: The Mediating Role of Body
      Mass Index, Sleep Duration, and Parent-Child Interaction.
AB  - OBJECTIVES: To examine the relationship between excessive screen time and
      psychosocial well-being in preschool children, and the potential mediating role
      of body mass index, sleep duration, and parent-child interaction. STUDY DESIGN: A
      cross-sectional survey was conducted in Shanghai, China using stratified random
      sampling design. A representative sample of 20 324 children aged 3-4 years old
      from 191 kindergartens participated in this study. Parents completed the
      Strengths and Difficulties Questionnaire and reported the child's time spent on
      screen exposure, sleep duration, height, weight, and parent-child interactive
      activities. RESULTS: Preschool children in Shanghai were exposed to 2.8 (95% CI
      2.7, 2.9) hours/day of screen time, with 78.6% (95% CI 77.8,79.3) exceeding 1
      hour/day and 53% (95% CI 52.0,53.9) exceeding 2 hours/day. Every additional hour
      of screen time was associated with increased risk for poor psychosocial well
      being. Body mass index, sleep duration, and parent-child interaction mediated the
      effect of excessive screen time on children's psychosocial well-being, among
      which parent-child interaction contributed most. Parent-child interaction could
      explain 28.1% of the effect on total difficulties and 58.6% on prosocial
      behavior. CONCLUSIONS: Excessive screen time during early childhood exists in
      Shanghai preschool children. Excessive screen exposure was associated with poor
      psychosocial well-being in preschool children via a number of mediators, mostly
      by reducing parent-child interaction.

PMID- 30100233
TI  - Energy and Protein Intake of Alzheimer's Disease Patients Compared to Cognitively
      Normal Controls: Systematic Review.
AB  - OBJECTIVES: Protein and energy malnutrition and unintended weight loss are
      frequently reported in patients with mild cognitive impairment (MCI) and
      Alzheimer's disease (AD). Possible underlying mechanisms include increased energy
      expenditure, altered uptake of nutrients, a reduced nutritional intake, or a
      combination of these 3. We aimed at systematically reviewing the literature to
      examine potential differences in energy and protein intake in patients with MCI
      and AD compared to controls as a possible mechanism for unintended weight loss.
      DESIGN: Systematic review and meta-analysis. SETTING: PubMed and Cochrane
      Electronic databases were searched from inception to September 2017 for case
      control studies. PARTICIPANTS: Patients with MCI or AD compared to cognitive
      healthy controls, all adhering to a Western dietary pattern. MEASUREMENTS: Energy
      and protein intake. RESULTS: The search resulted in 7 articles on patients with
      AD versus controls, and none on patients with MCI. Four articles found no
      differences in energy and protein intakes, 1 found higher intakes in patients
      with AD, and 1 article found lower intakes in patients with AD compared to
      controls. One article reported on intakes, but did not test differences. A meta
      analysis of the results indicated no difference between patients with AD and
      controls in energy [-8 kcal/d, 95% confidence interval (CI): -97, 81; P = .85],
      or protein intake (2 g/d, 95% CI: -4, 9; P = .47). However, heterogeneity was
      high (I2 > 70%), and study methodology was generally poor or moderate.
      CONCLUSION: Contrary to frequently reported unintended weight loss, our
      systematic review does not provide evidence for a lower energy or protein intake
      in patients with AD compared to controls. High heterogeneity of the results as
      well as of participant characteristics, setting, and study methods was observed.
      High-quality studies are needed to study energy and protein intake as a possible
      mechanism for unintended weight loss and malnutrition in both patients with MCI
      and AD.

PMID- 30100234
TI  - Discontinuation of Long-Term Antipsychotic Drug Use for Behavioral and
      Psychological Symptoms in Older Adults Aged 65 Years and Older With Dementia.
AB  - BACKGROUND: Antipsychotic drugs are often used to treat behavioral and
      psychological symptoms (BPSD) in adults aged 65 years and older with dementia,
      although there is uncertainty about the effectiveness of long-term use for this
      indication and there are concerns that they may cause harm. OBJECTIVES: To
      evaluate whether discontinuation of long-term antipsychotic drugs for BPSD is
      successful in adults aged 65 years and older with dementia. This article is based
      on a Cochrane review updated in 2018. DESIGN: A Cochrane systematic review and
      meta-analysis. SETTING AND PARTICIPANTS: Eight databases were searched in January
      2018 to identify 10 randomized controlled trials with 632 older adults. MEASURES:
      We used standard methodological procedures according to the Cochrane Handbook for
      Systematic Reviews of Interventions. We assessed the number of patients
      completing the study. We considered sustained withdrawal of antipsychotics until
      the end of the study period as successful outcome. RESULTS: Based on assessment
      of 7 studies (n = 446), discontinuation may make little or no difference to
      whether or not participants complete the study (low-quality evidence). In 2
      trials, including participants with psychosis, agitation, or aggression who had
      responded to antipsychotic treatment, discontinuation of antipsychotics was
      associated with a higher risk of leaving the study prematurely because of
      symptomatic relapse or a shorter time to symptomatic relapse. We found low
      quality evidence from 7 trials (n = 519) that discontinuation may make little or
      no difference to overall BPSD, measured using various scales. There was some
      evidence from subgroup analyses in 2 trials that discontinuation may be
      associated with a worsening of BPSD in participants with more severe BPSD at
      baseline. CONCLUSIONS: Our meta-analysis revealed that there is low-quality
      evidence that long-term antipsychotic drugs for BPSD may be successfully
      discontinued in most adults aged 65 and older.

PMID- 30100235
TI  - Urine therapy in Ayurveda: Ancient insights to modern discoveries for cancer
      regression.
AB  - Investigation of spontaneous regressions (SR) of cancer may explain host
      mechanisms of control by anticancer substance (A.C.S.). Documented human SR, of
      bladder cancer after uretero-sigmoidostomy and of uterine leiomyosarcoma after
      irreparable vesico-vaginal fistula, suggested the presence of A.C.S. in human
      urine. Animal experiments with urine in rat alveolar carcinoma and in mouse
      melanoma point to A.C.S. Urine therapy, as cited in Bhrigu-Samhita and used in
      some cases, needs to be followed up by systematic Reverse Pharmacology and
      analytical identification of A.C.S.

PMID- 30100236
TI  - Traditional practices and recent advances in Nadi Pariksha: A comprehensive
      review.
AB  - The significance of Nadi Pariksha is well understood and effectively used by
      Ayurveda practioners for assessing Tridoshas and various physiological and
      psychological states of the patient. The traditional texts Sarangadhara Samhita,
      YogaRatnakara, Basavarajeeyam and Bhavaprakasha have discussed the details of
      Nadi Pariksha in succinct set of slokas. Ayurveda has thousands of years of rich
      experience in Nadi Pariksha with strong literature support but is subjective in
      nature and the need for studying nadi with a scientific approach is well
      understood. Recently, pulse wave velocity has gained significant research
      interest as it is considered to be a strong indicator of cardiovascular disease;
      however, the relevance of pulse wave analysis to Nadi Pariksha has not been
      studied. In this review, traditional methods of Nadi Pariksha as defined in
      Ayurveda classics and the recent advances in pulse wave analysis are discussed.
      As per classical texts, qualities or properties of pulse such as pulse movement
      (gati), speed of the pulse (vega), stability of the pulse (sthiratva) and
      hardness of the artery (kathinya) play major role in Nadi Pariksha and in the
      current review these properties were analyzed and compared with the modern pulse
      parameters namely pulse wave velocity, pulse rate variability and arterial
      stiffness. The significance of pulse wave velocity in cardiovascular studies is
      discussed and the need for extending these studies to Ayurveda is highlighted.

PMID- 30100237
TI  - Time-delay estimation for SISO systems using SWsigma.
AB  - This paper addresses the time-delay estimation problem of SISO systems using
      uniformly sampled input-output data. A dependence measure known as Schweizer and
      Wolff's sigma (SWsigma) from the copula theory is employed to measure the
      dependence of the input-output data. The quantitative relation between the time
      delay and SWsigma is studied, and the time-delay is estimated given that the
      SWsigma of the input-output data reaches its maximum value when the time-delay is
      removed. The major advantage of our work is that no other parameters of the
      system must be estimated before or during the time-delay estimation process.
      Experiments and comparisons are used to verify the feasibility and effectiveness
      of the proposed method.

PMID- 30100238
TI  - Identification of hinging hyperplane autoregressive exogenous model using
      efficient mixed-integer programming.
AB  - A computationally efficient algorithm for hinging hyperplane autoregressive
      exogenous (HHARX) model identification via mixed-integer programming technique is
      proposed in this paper. The HHARX model is attractive since it accurately
      approximates a general nonlinear process as a sum of hinge functions and
      preserves the continuity even in a piecewise affine form. Traditional mixed
      integer programming-based method for HHARX model identification can only be
      applied on small-scale input/output datasets due to its significant computational
      demands. The contribution of this paper is to develop a sequential optimization
      approach to build accurate HHARX model more efficiently on a relatively large
      number of experimental data. Moreover, the proposed framework can handle more
      difficult and practical cases in piecewise model identification, such as: limited
      submodel switching, missing output data and specified steady state. Finally, the
      efficiency and accuracy of the proposed computational scheme are demonstrated
      through modeling of two simulated examples and a pilot-scale heat exchanger.

PMID- 30100239
TI  - Anti-tumour necrosis factor-induced cutaneous leishmaniasis in patient with
      psoriatic arthritis and uveitis.

PMID- 30100240
TI  - Neuropilin 1 ameliorates electrical remodeling at infarct border zones in rats
      after myocardial infarction.
AB  - BACKGROUND: Electrical remodeling at infarct border zone (IBZ) has been shown to
      contribute to the occurrence of ventricular arrhythmias after myocardial
      infarction (MI). Sema3A has been demonstrated to reduce the inducibility of
      ventricular arrhythmias. Neuropilin 1 (NRP1) is the receptor of Sema3A. In the
      present study, we investigated whether treatment with NRP1 can ameliorate
      electrical remodeling at IBZ after MI. METHODS AND RESULTS: Wistar rats underwent
      sham operation (n = 20), the ligation of left coronary artery (MI group, n = 30),
      MI with control adenovirus (Ad group, n = 30), and MI with NRP1 adenovirus (NRP1
      group, n = 30). Eight weeks after treatment, electrophysiological properties
      including heart rate variability (HRV), monophasic action potential duration
      (MAPD), effective refractory period (ERP) and the inducibility of ventricular
      arrhythmias and the expression of arrhythmia-related ion channel proteins
      including Kv4.2, Kv4.3, KChIP2 and Kir2.1 at the IBZ of the left ventricle were
      examined. Compared with the MI or Ad group, NRP1 significantly increased HRV and
      shortened MAPD and ERP (all P < 0.05). Inducibility of VT by electrophysiological
      study was significantly lower in the NRP1 group than in the MI or Ad group (P <
      0.05). The expression levels of Kv4.2, Kv4.3, KChIP2 and Kir2.1 proteins were
      significantly decreased in MI group and Ad group. In contrast, the expression
      levels of these proteins were restored in NRP1 group, which may represent the
      molecular basis of the NRP1-mediated inhibition of electrical remodeling.
      CONCLUSIONS: NRP1 can ameliorate electrical remodeling at IBZ after MI.

PMID- 30100241
TI  - The role of whole genome sequencing in monitoring antimicrobial resistance: A
      biosafety and public health priority in the Arabian Peninsula.
AB  - The recent declaration by the United Nations to establish an interagency
      coordination group (IACG) on antimicrobial resistance (AMR) emphasises the global
      nature of the AMR threat. Rapid dissemination and spread of AMR is exacerbated by
      the movements of humans, animals, foods and materials. International monitoring
      and surveillance of AMR indicates to policy makers, regulators and auditors the
      magnitude of the problem and also informs appropriate and mindful interventions
      that will impact public health policy and mitigate AMR. Identifying the drivers
      of AMR requires a 'one-health' approach to capture cross-sectoral utilization,
      phenotypic and genetic data. Capacity building in diagnostic and reference
      laboratories is required for traditional phenotypic testing as well as newer
      technologies (e.g. whole genome sequencing, WGS), in order to enhance the
      detection, characterisation, tracking and surveillance of AMR. The Gulf Health
      Council (GHC) for the cooperation council states have developed national AMR
      plans and will standardise pathogen identification and susceptibility testing to
      gain useful, reliable and comparable data. Additional plans are to establish, for
      the region, a state-of-the-art 'one-health' WGS service to identify and examine
      emerging AMR issues as well as the associated healthcare and financial burden(s).
      Currently, there is a paucity of WGS based research for tackling AMR challenges
      in the GHC countries. In this article, we have considered the current
      surveillance landscape and the potential role of whole genome sequencing (WGS)
      for monitoring antimicrobial resistance in the Arabian Peninsula. We highlighted
      the importance of using WGS for monitoring AMR in these countries as there
      remains a dearth of microbial genomic data and studies from the GHC countries.
      Development of WGS-based AMR surveillance is required to identify the burden and
      prevalence of AMR in the GHC countries.

PMID- 30100242
TI  - Clinical characteristics of patients with Ochrobactrum anthropi bloodstream
      infection in a Chinese tertiary-care hospital: A 7-year study.
AB  - BACKGROUND: Ochrobactrum anthropi has become an emerging pathogen for bloodstream
      infection (BSI). METHODS: From January 1st 2010 to June 30th 2017, inpatients
      with one or more blood cultures positive for O. anthropi isolates at Chinese
      People's Liberation Army General Hospital in Beijing, China, were enrolled in
      this study. Clinical and laboratory data were collected by reviewing electronic
      records. RESULTS: A total of 11 patients with O. anthropi BSI were identified, of
      which 10 patients survived. There were 6 males and 5 females, whose age ranged
      from 2 to 83 years. 7 infections were hospital-acquired. In 8 cases O. anthropi
      was the only pathogen. The most common symptoms of O. anthropi BSI were fever
      (100%) and disorders of consciousness (45.5%). All patients had undergone
      indwelling catheter placement. O. anthropi isolates in this study were most
      susceptible to levofloxacin (100%), ciprofloxacin (85.7%), imipenem (85.7%) and
      cotrimoxazole (85.7%), while they were widely resistant to penicillins and
      cephalosporins. CONCLUSIONS: O. anthropi BSI usually happens in patients with
      indwelling catheters, and often begins with no distinctive symptom or laboratory
      finding. O. anthropi seldom form polymicrobial BSIs. Quinolones and carbapenems
      are optimal antibiotics for O. anthropi BSI. Catheter removal is essential when
      O. anthropi BSI happens recurrently.

PMID- 30100244
TI  - The adaptor protein PID1 regulates receptor-dependent endocytosis of postprandial
      triglyceride-rich lipoproteins.
AB  - OBJECTIVE: Insulin resistance is associated with impaired receptor dependent
      hepatic uptake of triglyceride-rich lipoproteins (TRL), promoting
      hypertriglyceridemia and atherosclerosis. Next to low-density lipoprotein (LDL)
      receptor (LDLR) and syndecan-1, the LDLR-related protein 1 (LRP1) stimulated by
      insulin action contributes to the rapid clearance of TRL in the postprandial
      state. Here, we investigated the hypothesis that the adaptor protein
      phosphotyrosine interacting domain-containing protein 1 (PID1) regulates LRP1
      function, thereby controlling hepatic endocytosis of postprandial lipoproteins.
      METHODS: Localization and interaction of PID1 and LRP1 in cultured hepatocytes
      was studied by confocal microscopy of fluorescent tagged proteins, by indirect
      immunohistochemistry of endogenous proteins, by GST-based pull down and by
      immunoprecipitation experiments. The in vivo relevance of PID1 was assessed using
      whole body as well as liver-specific Pid1-deficient mice on a wild type or Ldlr
      deficient (Ldlr-/-) background. Intravital microscopy was used to study LRP1
      translocation in the liver. Lipoprotein metabolism was investigated by
      lipoprotein profiling, gene and protein expression as well as organ-specific
      uptake of radiolabelled TRL. RESULTS: PID1 co-localized in perinuclear endosomes
      and was found associated with LRP1 under fasting conditions. We identified the
      distal NPxY motif of the intracellular C-terminal domain (ICD) of LRP1 as the
      site critical for the interaction with PID1. Insulin-mediated NPxY
      phosphorylation caused the dissociation of PID1 from the ICD, causing LRP1
      translocation to the plasma membrane. PID1 deletion resulted in higher LRP1
      abundance at the cell surface, higher LDLR protein levels and, paradoxically,
      reduced total LRP1. The latter can be explained by higher receptor shedding,
      which we observed in cultured Pid1-deficient hepatocytes. Consistently, PID1
      deficiency alone led to increased LDLR-dependent endocytosis of postprandial
      lipoproteins and lower plasma triglycerides. In contrast, hepatic PID1 deletion
      on an Ldlr-/- background reduced lipoprotein uptake into liver and caused plasma
      TRL accumulation. CONCLUSIONS: By acting as an insulin-dependent retention
      adaptor, PID1 serves as a regulator of LRP1 function controlling the disposal of
      postprandial lipoproteins. PID1 inhibition provides a novel approach to lower
      plasma levels of pro-atherogenic TRL remnants by stimulating endocytic function
      of both LRP1 and LDLR in the liver.

PMID- 30100243
TI  - Intracellular lipids are an independent cause of liver injury and chronic kidney
      disease in non alcoholic fatty liver disease-like context.
AB  - OBJECTIVE: Ectopic lipid accumulation in the liver and kidneys is a hallmark of
      metabolic diseases leading to non-alcoholic fatty liver disease (NAFLD) and
      chronic kidney disease (CKD). Moreover, recent data have highlighted a strong
      correlation between NAFLD and CKD incidences. In this study, we use two mouse
      models of hepatic steatosis or CKD, each initiated independently of the other
      upon the suppression of glucose production specifically in the liver or kidneys,
      to elucidate the mechanisms underlying the development of CKD in the context of
      NAFLD-like pathology. METHODS: Mice with a deletion of G6pc, encoding glucose-6
      phosphatase catalytic subunit, specifically in the liver (L.G6pc-/- mice) or the
      kidneys (K.G6pc-/- mice), were fed with either a standard diet or a high fat/high
      sucrose (HF/HS) diet during 9 months. These mice represent two original models of
      a rare metabolic disease named Glycogen Storage Disease Type Ia (GSDIa) that is
      characterized by both NAFLD-like pathology and CKD. Two other groups of L.G6pc-/-
      and K.G6pc-/- mice were fed a standard diet for 6 months and then treated with
      fenofibrate for 3 months. Lipid and glucose metabolisms were characterized, and
      NAFLD-like and CKD damages were evaluated. RESULTS: Lipid depot exacerbation upon
      high-calorie diet strongly accelerated hepatic and renal pathologies induced by
      the G6pc-deficiency. In L.G6pc-/- mice, HF/HS diet increased liver injuries,
      characterized by higher levels of plasmatic transaminases and increased hepatic
      tumor incidence. In K.G6pc-/- mice, HF/HS diet increased urinary albumin and
      lipocalin 2 excretion and aggravated renal fibrosis. In both cases, the worsening
      of NAFLD-like injuries and CKD was independent of glycogen content. Furthermore,
      fenofibrate, via the activation of lipid oxidation significantly decreased the
      hepatic or renal lipid accumulations and prevented liver or kidney damages in
      L.G6pc-/- and K.G6pc-/- mice, respectively. Finally, we show that L.G6pc-/- mice
      and K.G6pc-/- mice developed NAFLD-like pathology and CKD independently.
      CONCLUSIONS: This study highlights the crucial role that lipids play in the
      independent development of both NAFLD and CKD and demonstrates the importance of
      lipid-lowering treatments in various metabolic diseases featured by lipid load,
      from the "rare" GSDIa to the "epidemic" morbid obesity or type 2 diabetes.

PMID- 30100247
TI  - Native hip dislocation at acetabular fracture predicts poor long-term outcome.
AB  - AIM: The aim of this study was to evaluate the long-term clinical outcomes and
      complications following an acetabular fracture associated with a posterior hip
      dislocation compared to those without dislocation. PATIENTS & METHODS: A
      retrospective cohort study of 113 patients (mean age 42 (14-95), 77% male) with
      acetabular fracture dislocations compared to 367 patients with acetabular
      fractures without dislocation (mean age 54 (16-100), 66% male) treated from 1988
      to 2010. Patient characteristics, complications, reoperations, and conversion to
      total hip arthroplasty (THA) were recorded. Long term patient reported outcomes
      (Oxford Hip Score and SF-12) were measured at mean follow up 9.7 years (5-26).
      RESULTS: At long-term follow up 12/113 (11%) patients had died and 22/113 (19%)
      were lost. Isolated posterior wall fracture was the most common fracture
      associated with dislocation. Patients with dislocation were more likely to be
      younger and male with higher Injury Severity Scores (ISS). There was no
      significant difference in radiographic post-traumatic osteoarthritis development
      between fractures with and without dislocation (p = 0.246). Sciatic nerve palsy
      (12% Vs 1%, p < 0.001) and avascular necrosis (AVN) (11% Vs 1%, p < 0.001) were
      more common when dislocation was present. AVN was associated with increasing age
      and hypotension on arrival to the emergency department. Ten-year native hip
      survival was worse following fracture dislocations compared to fractures without
      dislocation: 75.1% (65.7-84.5 95% CI) Vs 90.7% (87.0-94.4), p < 0.001.
      Significant predictors of THA requirement were older age, particularly age >55
      years at fracture, and increased ISS. Long-term OHS was worse in fractures with
      dislocations (33.6 +/- 13.1 Vs 37.0 +/- 14.0, p = 0.016). CONCLUSION: Acetabular
      fractures with an associated dislocation have worse long-term functional outcomes
      with higher rates of complications and conversion to late THA compared to
      acetabular fractures without a dislocation.

PMID- 30100245
TI  - Cartilage oligomeric matrix protein is differentially expressed in human
      subcutaneous adipose tissue and regulates adipogenesis.
AB  - OBJECTIVE: The composition of the extracellular matrix (ECM) impacts adipocyte
      function and might determine adipose tissue (AT) function and distribution.
      Cartilage oligomeric matrix protein (COMP), a matricellular protein usually
      studied in bone and cartilage, is highly differentially expressed between
      subcutaneous abdominal and gluteal AT. This study aimed to explore COMP's role in
      human subcutaneous abdominal and gluteal AT and preadipocyte biology. METHODS:
      COMP mRNA levels were measured in whole AT and immortalised preadipocytes via
      quantitative (q)-PCR. Tissue and cellular COMP protein were measured via Western
      blot and immunohistochemistry; plasma COMP was measured by ELISA. The effect of
      COMP on adipogenesis in immortalised preadipocytes was evaluated by qPCR of
      adipogenic markers and cellular triacylglycerol (TAG) accumulation. RESULTS: qPCR
      analysis of paired subcutaneous abdominal and gluteal AT biopsies (n = 190)
      across a range of BMI (20.7-45.5 kg/m2) indicated ~3-fold higher COMP expression
      in gluteal AT (P = 1.7 * 10-31); protein levels mirrored this.
      Immunohistochemistry indicated COMP was abundant in gluteal AT ECM and co
      localised with collagen-1. AT COMP mRNA levels and circulating COMP protein
      levels were positively associated with BMI/adiposity but unrelated to AT
      distribution. COMP expression changed dynamically during adipogenesis (time *
      depot, P = 0.01). Supplementation of adipogenic medium with exogenous COMP
      protein (500 ng/ml) increased PPARG2 expression ~1.5-fold (P = 0.0003) and TAG
      accumulation ~1.25-fold in abdominal and gluteal preadipocytes (P = 0.02).
      CONCLUSIONS: We confirmed that COMP is an ECM protein which is differentially
      expressed between subcutaneous abdominal and gluteal AT. Despite its depot
      specific expression pattern, however, AT COMP mRNA levels and plasma COMP
      concentration correlated positively with overall obesity but not body fat
      distribution. Exogenous COMP enhanced adipogenesis. These data identify COMP as a
      novel regulator of AT and highlight the importance of the ECM to AT biology.

PMID- 30100248
TI  - How does cochlear implantation affect five vestibular end-organ functions and
      dizziness?
AB  - OBJECTIVE: To evaluate all five vestibular end-organ functions (lateral,
      anterior, posterior semicircular canal, utricule, and saccule) and to investigate
      the relationship between Dizziness Handicap Inventory (DHI) and vestibular
      functions prior to CI (cochlear implantation) and at postoperative day 3 and
      month 3. METHODS: A total of 42 patients (age 16-70years) with normal vestibular
      functions preoperatively and undergoing unilateral CI were included in this
      prospective descriptive study. Video head impulse test (vHIT) for three
      semicircular canal (SSC) functions, ocular vestibular-evoked myogenic potential
      (oVEMP) for utricule function, cervical vestibular-evoked myogenic potential
      (cVEMP) for saccule function and DHI for subjective vertigo symptoms were
      performed prior to CI and at postoperative day 3 and month 3. RESULTS: There was
      a significant impairment of vestibular function in 12 patients (28.5%) on the
      implantation side and significant DHI increase was observed in 13 of 42 (30.9%)
      patients at postoperative day 3 after CI (p<0.05). We found SSC dysfunction in 7
      patients (16,6%) who underwent observation with vHIT, saccule dysfunction in 8
      patients (19%) with cVEMP and utricule dysfunction in 5 patients (11.9%) with
      oVEMP on the operated side 3days after surgery (p<0.05). Posterior SSC functions
      (5 patients) were more affected than lateral SSC functions (3 patients). At
      postoperative month 3, six patients (14.2%) still had deteriorating results in
      the objective tests and significant DHI increase was continued in 4 (9.5%)
      patients (p<0.05). The deterioration in vHIT continued in only 1 (2.3%) patient
      (p>0.05). The deterioration in cVEMP continued in 5 (11.9%) patients (p<0.05).
      The deterioration in oVEMP continued in 2 (4.7%) patients (p>0.05). There was a
      significant correlation between DHI and objective vestibular tests both in the
      early and late postoperative period (r=0.795; p<0.05). CONCLUSION: Our study
      showed that both canal and otolith functions can be damaged after CI especially
      in the early postoperative period. Surprisingly, posterior SSC functions were
      more affected than lateral SSC. Therefore, a gold standard vestibular test
      battery that can evaluate each of three SSC canals and two otoliths functions is
      essential. Since a single vestibular test for this purpose is not available, we
      recommend the use of the three available vestibular tests together. This test
      battery, which is capable of evaluating five vestibular end-organ functions in
      preoperative and postoperative vestibular evaluations, can provide more accurate
      results not only for CI but also for most otologic surgeries.

PMID- 30100246
TI  - TGF-beta receptor 1 regulates progenitors that promote browning of white fat.
AB  - OBJECTIVE: Beige/brite adipose tissue displays morphological characteristics and
      beneficial metabolic traits of brown adipose tissue. Previously, we showed that
      TGF-beta signaling regulates the browning of white adipose tissue. Here, we
      inquired whether TGF-beta signals regulated presumptive beige progenitors in
      white fat and investigated the TGF-beta regulated mechanisms involved in beige
      adipogenesis. METHODS: We deleted TGF-beta receptor 1 (TbetaRI) in adipose tissue
      (TbetaRIAdKO mice) and, using flow-cytometry based assays, identified and
      isolated presumptive beige progenitors located in the stromal vascular cells of
      white fat. These cells were molecularly characterized to examine beige/brown
      marker expression and to investigate TGF-beta dependent mechanisms. Further, the
      cells were transplanted into athymic nude mice to examine their adipogenesis
      potential. RESULTS: Deletion of TbetaRI promotes beige adipogenesis while
      reducing the detrimental effects of high fat diet feeding. Interaction of TGF
      beta signaling with the prostaglandin pathway regulated the appearance of beige
      adipocytes in white fat. Using flow cytometry techniques and stromal vascular
      fraction from white fat, we isolated presumptive beige stem/progenitor cells
      (iBSCs). Upon genetic or pharmacologic inhibition of TGF-beta signaling, these
      cells express high levels of predominantly beige markers. Transplantation of
      TbetaRI-deficient stromal vascular cells or iBSCs into athymic nude mice followed
      by high fat diet feeding and stimulation of beta-adrenergic signaling via
      CL316,243 injection or cold exposure promoted robust beige adipogenesis in vivo.
      CONCLUSIONS: TbetaRI signals target the prostaglandin network to regulate
      presumptive beige progenitors in white fat capable of developing into beige
      adipocytes with functional attributes. Controlled inhibition of TbetaRI signaling
      and concomitant PGE2 stimulation has the potential to promote beige adipogenesis
      and improve metabolism.

PMID- 30100254
TI  - Behavioral Strategy Determines Frontal or Posterior Location of Short-Term Memory
      in Neocortex.
AB  - The location of short-term memory in mammalian neocortex remains elusive. Here we
      show that distinct neocortical areas maintain short-term memory depending on
      behavioral strategy. Using wide-field and single-cell calcium imaging, we
      measured layer 2/3 neuronal activity in mice performing a whisker-based texture
      discrimination task with delayed response. Mice either deployed an active
      strategy-engaging their body toward the approaching texture-or passively awaited
      the touch. Independent of strategy, whisker-related posterior areas encoded
      choice early after touch. During the delay, in contrast, persistent cortical
      activity was located medio-frontally in active trials but in a lateral posterior
      area in passive trials. Perturbing these areas impaired performance for the
      associated strategy and also provoked strategy switches. Frontally maintained
      information related to future action, whereas activity in the posterior cortex
      reflected past stimulus identity. Thus, depending on behavioral strategy,
      cortical activity is routed differentially to hold information either frontally
      or posteriorly before converging to similar action.

PMID- 30100255
TI  - Striatal Microstimulation Induces Persistent and Repetitive Negative Decision
      Making Predicted by Striatal Beta-Band Oscillation.
AB  - Persistent thoughts inducing irrationally pessimistic and repetitive decisions
      are often symptoms of mood and anxiety disorders. Regional neural hyperactivities
      have been associated with these disorders, but it remains unclear whether there
      is a specific brain region causally involved in these persistent valuations.
      Here, we identified potential sources of such persistent states by
      microstimulating the striatum of macaques performing a task by which we could
      quantitatively estimate their subjective pessimistic states using their choices
      to accept or reject conflicting offers. We found that this microstimulation
      induced irrationally repetitive choices with negative evaluations. Local field
      potentials recorded in the same microstimulation sessions exhibited modulations
      of beta-band oscillatory activity that paralleled the persistent negative states
      influencing repetitive decisions. These findings demonstrate that local striatal
      zones can causally affect subjective states influencing persistent negative
      valuation and that abnormal beta-band oscillations can be associated with
      persistency in valuation accompanied by an anxiety-like state.

PMID- 30100257
TI  - Antisense oligonucleotide targeting of mRNAs encoding ENaC subunits alpha, beta,
      and gamma improves cystic fibrosis-like disease in mice.
AB  - BACKGROUND: The epithelial sodium channel ENaC consists of three subunits encoded
      by Scnn1a, Scnn1b, and Scnn1g and increased sodium absorption through this
      channel is hypothesized to lead to mucus dehydration and accumulation in cystic
      fibrosis (CF) patients. METHODS: We identified potent and specific antisense
      oligonucleotides (ASOs) targeting mRNAs encoding the ENaC subunits and evaluated
      these ASOs in mouse models of CF-like lung disease. RESULTS: ASOs designed to
      target mRNAs encoding each ENaC subunit or a control ASO were administered
      directly into the lungs of mice. The reductions in ENaC subunits correlated well
      with a reduction in amiloride sensitive channel conductance. In addition, levels
      of mucus markers Gob5, AGR2, Muc5ac, and Muc5b, periodic acid-Schiff's reagent
      (PAS) goblet cell staining, and neutrophil recruitment were reduced and lung
      function was improved when levels of any of the ENaC subunits were decreased.
      CONCLUSIONS: Delivery of ASOs targeting mRNAs encoding each of the three ENaC
      subunits directly into the lung improved disease phenotypes in a mouse model of
      CF-like lung disease. These findings suggest that targeting ENaC subunits could
      be an effective approach for the treatment of CF.

PMID- 30100258
TI  - Reserve stem cell population in intestinal crypts found to be consistently small
      by analysis of in vivo clonogenic assays with a biomathematical dynamic model.
AB  - BACKGROUND AND PURPOSE: The high plasticity of the intestinal epithelium is
      maintained by a resilient reserve stem cell population, whose extent and biology
      are a matter of ongoing debate. The in vivo clonogenic assay (IVCA), presents a
      well established and efficient analysis of radiation insult to the intestinal
      crypts. However, we found that inadequate mathematical analysis over the last
      four decades led to systematic errors and contradictory results in estimates of
      radio-sensitivity and size of the reserve stem cell pool. MATERIAL AND METHODS:
      We devised a refinement of the IVCA via development of a biomathematical model
      that delivers a full statistical dynamic description of epithelial radiation
      injury and subsequent regeneration. We validated the model against cellular and
      crypt distribution statistics obtained from IVCA experiments and through
      systematic re-analysis of experimental data from 27 publications. RESULTS: A full
      dynamic description of the evolution of stem cell niche population statistics is
      obtained. A systematic re-analysis reveals a consistent clonogenic content of the
      crypt of 31+/-6 cells. The stem cell reserve manifests to be, contrary to prior
      predictions, radio-resistant: alpha=(0.22+/-0.04) Gy-1. CONCLUSION: We
      established a precision tool for the quantitative analysis of radiation insult to
      the intestinal crypts, which we employ to show that the reserve stem cell
      population is small, radio-resistant, and remarkably immutable against a large
      variety of interventions. The increased resolution of the model allows not only a
      reduction of the number of animals by about 75%, but also to quantify
      experimentally the influence of additional agents on damage and on regeneration
      of the stem cell niche.

PMID- 30100259
TI  - Patient-Centered Outcomes in the Management of Anemia: A Scoping Review.
AB  - Anemia is a frequently diagnosed condition that may be a symptom of or
      complication of many illnesses affecting patients of all demographics. Anemia can
      lead to both worsened clinical outcomes and reduced quality of life. Patient
      reported outcome measures (PROMs) are methodological tools used to capture the
      impact of disease on patient well-being. Use of PROMs in medical research is
      becoming more common as it is increasingly recognized that disease outcomes of
      interest to researchers and clinicians are not always consistent with patients'
      greatest concerns related to their diseases. We conducted a scoping review to
      characterize the studies that have evaluated patient-centered outcomes using
      PROMs in patients undergoing treatment for anemia. We conducted a search of
      Medline (Ovid), EMBASE (Ovid), PsychINFO, and CINAHL databases for studies
      published until January 2017 that investigated an intervention to treat anemia in
      any patient population and used at least 1 PROM to evaluate patient-centered
      outcomes. A descriptive synthesis was performed to characterize the PROMs used
      and to evaluate the quality of patient-centered outcome (PCO) reporting. Of the
      3224 studies identified in the initial search, 130 met all eligibility criteria.
      We found that the population most frequently studied was oncology patients (46.2%
      of studies). The therapy for anemia evaluated in the most studies was
      erythropoietin-stimulating agents (77.7% of studies). The most commonly used PROM
      was the Functional Assessment of Cancer Therapy/Functional Assessment of Chronic
      Illness Therapy tool (46.9%), and the majority of studies used only 1 PROM tool
      (53.1%). We found significant variability in the quality of PCO reporting across
      all included studies. Improved methodologic rigor in the assessment of PCOs in
      anemia management is needed in future studies.

PMID- 30100260
TI  - Factors and outcomes associated with candidemia caused by non-albicans Candida
      spp versus Candida albicans in children.
AB  - BACKGROUND: Candidemia in children caused by non-albicans Candida (NAC) spp is
      increasing in prevalence, but the relevant information is limited. METHODS: All
      isolates of pediatric candidemia from a medical center in Taiwan between 2003 and
      2015 were enrolled. The characteristics of patients with NAC and Candida albicans
      candidemia (CAC) were compared. RESULTS: Among the 319 episodes of candidemia
      occurring in 262 patients, C albicans accounted for 46.4%. The NAC and CAC groups
      had no significant differences in demographics, underlying diseases, most risk
      factors, and clinical characteristics. Patients in the NAC group were
      significantly more likely to have fluconazole exposure (14.0% vs 6.8%,
      respectively; P = .045), and NAC species accounted for 70.2% of all recurrent
      episodes. NAC candidemia had a longer duration of candidemia (median, 3.0 vs 1.0
      days after effective antifungal treatment, respectively; P = .001), slower
      responses to antifungal treatment, and a higher rate of treatment failure than
      CAC. However, the 2 groups had similar 30-day candidemia-attributable mortality
      rates. After multivariate logistic regression, longer duration of central venous
      catheter was the independent risk factor for NAC candidemia in children (odds
      ratio, 1.21; 95% confidence interval, 1.08-1.35 for every 10-day increment).
      CONCLUSIONS: NAC species collectively have emerged as the predominant pathogens
      of candidemia in children. Prolonged use of a central venous catheter is
      associated with an increased risk of candidemia caused by NAC species.

PMID- 30100256
TI  - A Highly Sensitive A-Kinase Activity Reporter for Imaging Neuromodulatory Events
      in Awake Mice.
AB  - Neuromodulation imposes powerful control over brain function, and cAMP-dependent
      protein kinase (PKA) is a central downstream mediator of multiple
      neuromodulators. Although genetically encoded PKA sensors have been developed,
      single-cell imaging of PKA activity in living mice has not been established.
      Here, we used two-photon fluorescence lifetime imaging microscopy (2pFLIM) to
      visualize genetically encoded PKA sensors in response to the neuromodulators
      norepinephrine and dopamine. We screened available PKA sensors for 2pFLIM and
      further developed a variant (named tAKARalpha) with increased sensitivity and a
      broadened dynamic range. This sensor allowed detection of PKA activation by
      norepinephrine at physiologically relevant concentrations and kinetics, and by
      optogenetically released dopamine. In vivo longitudinal 2pFLIM imaging of
      tAKARalpha tracked bidirectional PKA activities in individual neurons in awake
      mice and revealed neuromodulatory PKA events that were associated with
      wakefulness, pharmacological manipulation, and locomotion. This new sensor
      combined with 2pFLIM will enable interrogation of neuromodulation-induced PKA
      signaling in awake animals. VIDEO ABSTRACT.

PMID- 30100262
TI  - Trisomy 21 Represses Cilia Formation and Function.
AB  - Trisomy 21 (T21) is the most prevalent human chromosomal disorder, causing a
      range of cardiovascular, musculoskeletal, and neurological abnormalities.
      However, the cellular processes disrupted by T21 are poorly understood.
      Consistent with the clinical overlap between T21 and ciliopathies, we discovered
      that T21 disrupts cilia formation and signaling. Cilia defects arise from
      increased expression of Pericentrin, a centrosome scaffold and trafficking
      protein encoded on chromosome 21. Elevated Pericentrin is necessary and
      sufficient for T21 cilia defects. Pericentrin accumulates at centrosomes and
      dramatically in the cytoplasm surrounding centrosomes. Centrosome Pericentrin
      recruits more gamma-tubulin and enhances microtubules, whereas cytoplasmic
      Pericentrin assembles into large foci that do not efficiently traffic. Moreover,
      the Pericentrin-associated cilia assembly factor IFT20 and the ciliary signaling
      molecule Smoothened do not efficiently traffic to centrosomes and cilia. Thus,
      increased centrosome protein dosage produces ciliopathy-like outcomes in T21
      cells by decreasing trafficking between the cytoplasm, centrosomes, and cilia.

PMID- 30100261
TI  - PINK1 and PARK2 Suppress Pancreatic Tumorigenesis through Control of
      Mitochondrial Iron-Mediated Immunometabolism.
AB  - Pancreatic cancer is an aggressive malignancy with changes in the tumor
      microenvironment. Here, we demonstrate that PINK1 and PARK2 suppressed pancreatic
      tumorigenesis through control of mitochondrial iron-dependent immunometabolism.
      Using mouse models of spontaneous pancreatic cancer, we show that depletion of
      Pink1 and Park2 accelerates mutant Kras-driven pancreatic tumorigenesis. PINK1
      PARK2 pathway-mediated degradation of SLC25A37 and SLC25A28 increases
      mitochondrial iron accumulation, which leads to the HIF1A-dependent Warburg
      effect and AIM2-dependent inflammasome activation in tumor cells. AIM2-mediated
      HMGB1 release further induces expression of CD274/PD-L1. Consequently,
      pharmacological administration of mitochondrial iron chelator, anti-HMGB1
      antibody, or genetic depletion of Hif1a or Aim2 in pink1-/- and park2-/- mice
      confers protection against pancreatic tumorigenesis. Low PARK2 expression and
      high SLC25A37 and AIM2 expression are associated with poor prognosis in patients
      with pancreatic cancer. These findings suggest that disrupted mitochondrial iron
      homeostasis may contribute to cancer development and hence constitute a target
      for therapeutic intervention.

PMID- 30100263
TI  - FGF20-Expressing, Wnt-Responsive Olfactory Epithelial Progenitors Regulate
      Underlying Turbinate Growth to Optimize Surface Area.
AB  - The olfactory epithelium (OE) is a neurosensory organ required for the sense of
      smell. Turbinates, bony projections from the nasal cavity wall, increase the
      surface area within the nasal cavity lined by the OE. Here, we use engineered
      fibroblast growth factor 20 (Fgf20) knockin alleles to identify a population of
      OE progenitor cells that expand horizontally during development to populate all
      lineages of the mature OE. We show that these Fgf20-positive epithelium-spanning
      progenitor (FEP) cells are responsive to Wnt/beta-Catenin signaling. Wnt
      signaling suppresses FEP cell differentiation into OE basal progenitors and their
      progeny and positively regulates Fgf20 expression. We further show that FGF20
      signals to the underlying mesenchyme to regulate the growth of turbinates. These
      studies thus identify a population of OE progenitor cells that function to scale
      OE surface area with the underlying turbinates.

PMID- 30100265
TI  - In Vivo Evidence for ATPase-Dependent DNA Translocation by the Bacillus subtilis
      SMC Condensin Complex.
AB  - Structural maintenance of chromosomes (SMC) complexes shape the genomes of
      virtually all organisms, but how they function remains incompletely understood.
      Recent studies in bacteria and eukaryotes have led to a unifying model in which
      these ring-shaped ATPases act along contiguous DNA segments, processively
      enlarging DNA loops. In support of this model, single-molecule imaging
      experiments indicate that Saccharomyces cerevisiae condensin complexes can
      extrude DNA loops in an ATP-hydrolysis-dependent manner in vitro. Here, using
      time-resolved high-throughput chromosome conformation capture (Hi-C), we
      investigate the interplay between ATPase activity of the Bacillus subtilis SMC
      complex and loop formation in vivo. We show that point mutants in the SMC
      nucleotide-binding domain that impair but do not eliminate ATPase activity not
      only exhibit delays in de novo loop formation but also have reduced rates of
      processive loop enlargement. These data provide in vivo evidence that SMC
      complexes function as loop extruders.

PMID- 30100266
TI  - An Antiviral Branch of the IL-1 Signaling Pathway Restricts Immune-Evasive Virus
      Replication.
AB  - Virulent pathogens often cause the release of host-derived damage-associated
      molecular patterns (DAMPs) from infected cells. During encounters with immune
      evasive viruses that block inflammatory gene expression, preformed DAMPs provide
      backup inflammatory signals that ensure protective immunity. Whether DAMPs
      exhibit additional backup defense activities is unknown. Herein, we report that
      viral infection of barrier epithelia (keratinocytes) elicits the release of
      preformed interleukin-1 (IL-1) family cytokines, including the DAMP IL-1alpha.
      Mechanistic studies revealed that IL-1 acts on skin fibroblasts to induce an
      interferon (IFN)-like state that restricts viral replication. We identified a
      branch in the IL-1 signaling pathway that induces IFN-stimulated gene expression
      in infected cells and found that IL-1 signaling is necessary to restrict viral
      replication in human skin explants. These activities are most important to
      control immune-evasive virus replication in fibroblasts and other barrier cell
      types. These findings highlight IL-1 as an important backup antiviral system to
      ensure barrier defense.

PMID- 30100264
TI  - Poly(ADP-Ribose) Prevents Pathological Phase Separation of TDP-43 by Promoting
      Liquid Demixing and Stress Granule Localization.
AB  - In amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD),
      cytoplasmic aggregates of hyperphosphorylated TDP-43 accumulate and colocalize
      with some stress granule components, but how pathological TDP-43 aggregation is
      nucleated remains unknown. In Drosophila, we establish that downregulation of
      tankyrase, a poly(ADP-ribose) (PAR) polymerase, reduces TDP-43 accumulation in
      the cytoplasm and potently mitigates neurodegeneration. We establish that TDP-43
      non-covalently binds to PAR via PAR-binding motifs embedded within its nuclear
      localization sequence. PAR binding promotes liquid-liquid phase separation of TDP
      43 in vitro and is required for TDP-43 accumulation in stress granules in
      mammalian cells and neurons. Stress granule localization initially protects TDP
      43 from disease-associated phosphorylation, but upon long-term stress, stress
      granules resolve, leaving behind aggregates of phosphorylated TDP-43. Finally,
      small-molecule inhibition of Tankyrase-1/2 in mammalian cells inhibits formation
      of cytoplasmic TDP-43 foci without affecting stress granule assembly. Thus,
      Tankyrase inhibition antagonizes TDP-43-associated pathology and
      neurodegeneration and could have therapeutic utility for ALS and FTD.

PMID- 30100267
TI  - The intensification of amyloglucosidase-based saccharification by ultrasound.
AB  - The present report studied the role of ultrasound (US) energy in the
      amyloglucosidase-based starch hydrolysis using two complementary approaches: (i)
      in the activity of six commercially-available amyloglucosidases (using soluble
      starch as substrate), and (ii) in the hydrolysis of four pure starches from
      different botanical sources. This corresponds to the first systematic evaluation
      of the role of US in starch hydrolysis mediated by amyloglucosidase, being a
      consequence of our previous report that assessed the effect of US in the activity
      of alpha-amylase (LWT - Food Science and Technology 84 (2017) 674-685). Regarding
      amlyloglucosidases, three enzymes obtained from Aspergillus niger (AN1-AN3), and
      Spirizyme Achieve (SPA), Spirizyme Fuel (SPF) and Spirizyme Ultra (SPU) were
      submitted to a Box-Behnken experimental design in order to establish the optimum
      conditions for their maximum activity. In the presence of US, we found both
      inactivation and activation, ranging from -88% (AN3) to 699% (SPA). The US
      promoted the enzyme activity when combined with lower temperatures (40-60 
      degrees C), with a marked effect in Spirizyme enzymes. Based on the optimum
      conditions established by the experimental design, we also evaluated the role of
      US in the glucose yield resulting from the hydrolysis of pure starches (corn,
      rice, potato, wheat). In this case, US led to higher glucose yields in all
      conditions tested. The enhancement factors observed ranged from 1.2 (AN1, rice
      starch) to 65 (SPA, potato starch) times. We compared these findings with
      previous reports, which highlighted the role of US in intensifying
      amyloglucosidase-based saccharification in mild conditions, by simultaneously
      influencing both enzyme and substrate. Hence, US power has to be fine-tuned for
      each particular enzyme in order to maximize process intensification.

PMID- 30100268
TI  - FDA Approval of Pimavanserin: Response to Absence of Evidence Versus Evidence of
      Absence-Pimavanserin and the SAPS-PD.

PMID- 30100269
TI  - A brief illustration of the official national standards for the safe use of
      cupping therapy (Hijama) in Saudi Arabia.
AB  - Cupping therapy (Hijama in Arabic) is a popular traditional treatment especially
      in Asia, the Middle East and Central Europe. Traditionally, cupping therapy has
      been one of the most used practices in Saudi Arabia. Standardization of the
      practice of cupping therapy is a very important step to eliminate or reduce any
      adverse events related to cupping. This article gives a brief illustration and
      highlights the important points of the first accredited Saudi Arabian standards
      for the safe use of cupping equipment and its applications.

PMID- 30100270
TI  - Pheochromocytoma: When to search a germline defect?
AB  - With advances in our understanding of the genetics of pheochromocytomas and
      paragangliomas (PPGL), the answer to the question 'Should we search for a
      germline defect in patients diagnosed with PPGL?' has changed considerably since
      the end of the last century, when PPGL was thought to be inherited in only 10% of
      cases, because we now know that about 40% of patients carry a germline mutation
      in one PPGL susceptibility gene. PPGL is now considered to be the most highly
      heritable neuroendocrine tumour, with more than 15 susceptibility genes
      identified, and current guidelines recommend genetic testing during initial tests
      on PPGL patients. This genetic testing is routinely carried out by next
      generation sequencing methods, making it possible to genotype a large number of
      susceptibility genes in a single analysis. Positive results for any of the known
      susceptibility genes are an indication for specific follow-up of the inherited
      disease and for the organization of predictive genetic testing in the patient's
      relatives. The development of precision medicine for PPGL, based on the molecular
      profile of the tumor, should become possible in the near future.

PMID- 30100271
TI  - Cerebral Neuromonitoring During Cardiac Surgery: A Critical Appraisal With an
      Emphasis on Near-Infrared Spectroscopy.
AB  - Neurological complications of cardiac surgery have a large effect on patient
      outcomes. In this review, the value of several modes of central nervous system
      monitoring for improving perioperative care is critiqued. The
      electroencephalogram (EEG) has been used as a means for detecting brain ischemia.
      Even though EEG changes are specific for ischemia, the reliability is tempered by
      many confounding factors. The effectiveness of the processed EEG for ensuring
      amnesia during surgery is controversial, but it may have value for optimizing
      anesthetic dose and thus reducing the risk for delirium. Transcranial Doppler may
      be beneficial in confirming flow to both cerebral hemispheres during antegrade
      cerebral perfusion such as during aortic arch surgery and in detecting cerebral
      emboli. Transcranial Doppler can be used for monitoring cerebral autoregulation,
      allowing for individualization of blood pressure targets during surgery. Measures
      of adequacy of cerebral oxygen balance include jugular bulb venous oxygen
      saturation and near-infrared spectroscopy monitoring. Both monitors have
      limitations that reduce the sensitivity for detecting brain ischemia. Because
      near-infrared spectroscopy-measured regional cerebral oxygen saturation does not
      distinguish arterial from venous blood, these measurements reflect the adequacy
      of oxygen delivery versus demand. Over short periods, filtered regional cerebral
      oxygen saturation data may provide a clinically feasible method of monitoring
      cerebral autoregulation that overcomes many limitations of transcranial Doppler.
      Ongoing studies have demonstrated that the latter methodology for determining
      perioperative blood pressure targets has large potential for reducing organ
      injury from cardiac surgery.

PMID- 30100272
TI  - Renal Cell Carcinoma Pseudoprogression with Clinical Deterioration: To Hospice
      and Back.

PMID- 30100274
TI  - Anticipating the 5th International Fascia Research Congress.

PMID- 30100273
TI  - Predicting the necessity of adding catheters to intracavitary brachytherapy for
      women undergoing definitive chemoradiation for locally advanced cervical cancer.
AB  - PURPOSE: To identify if baseline patient or magnetic resonance imaging (MRI)
      features can predict which women are at risk for inadequate tumor coverage with
      only intracavitary tandem and ovoid (T + O) brachytherapy and to correlate tumor
      coverage with clinical outcomes. METHODS AND MATERIALS: We performed a
      retrospective study of 50 women with cervical cancer treated with chemoradiation
      at a single institution between January 2014 and December 2015. All patients had
      a 3T-MRI performed at baseline (MRI1) and at the completion of external beam
      radiation therapy (MRI2). Gross tumor volume initial (GTV-Tinit) was measured on
      MRI1 and high-risk clinical tissue volume (CTVHR) on MRI2. CTVHR extending beyond
      point A was classified as too large for adequate coverage with T + O and
      requiring interstitial needles. Multivariate analysis was performed to determine
      predictive factors of inadequate coverage. Kaplan-Meier and Cox Regression were
      performed to correlate inadequate coverage with outcomes. RESULTS: Mean patient
      age was 49.2 +/- 13.2 years, and 84% had Federation of Gynecology and Obstetrics
      IIB/IIIB disease. Forty-two percent of women were estimated to have inadequate
      tumor coverage with T + O brachytherapy. The GTV-Tinit volume and dimensions
      (superior-inferior, left-right, anterior-posterior) on MRI1 were all important
      predictive factors of inadequate coverage on multivariate analysis. Receiver
      operating characteristics curves identified optimal thresholds of superior
      inferior >= 4.5 cm (area under the curve [AUC] = 0.718), left-right >= 4.5 cm
      (AUC = 0.745), anterior-posterior >= 5.0 cm (AUC = 0.767), and GTV-Tinit >= 85
      cm3 (AUC = 0.842). Patients with inadequate coverage had worse clinical outcomes.
      CONCLUSIONS: Baseline MRI tumor size may predict inadequate CTVHR coverage at the
      time of brachytherapy (i.e., the need for interstitial needles). This may help
      identify a subset of women requiring early referral to adequately resourced
      centers to improve clinical outcomes.

PMID- 30100276
TI  - Skin burns following cryotherapy in misdiagnosed pediatric injuries.
AB  - Superficial local cryotherapy is frequently and safely used for pain relief
      following musculoskeletal injury or disease. However, serious skin complications
      have been reported in adults following inappropriate application. Skin burns
      following superficial local cryotherapy have not been previously reported in
      children. The consequences of inappropriate use of various forms of cryotherapy
      in four children following sport injuries are presented. They were all primarily
      misdiagnosed with a soft tissue injury. The incorrect usage was due to the high
      severity of the local symptoms and signs. They were all referred with partial
      thickness skin burns. Diagnosis on referral indicated a bone injury in all of
      them. The value of the initial clinical examination is emphasized considering
      that fractures, including physeal injuries, are more common than ligamentous
      lesions, and the high incidence of the radiographically occult acute injuries in
      children. The use of superficial local cryotherapy following injuries in children
      should always follow the rules of proper usage and should be avoided in cases
      that the clinical examination cannot exclude a potential sprain or fracture to
      prevent further ligament, joint or bone damaging.

PMID- 30100275
TI  - Addressing the ongoing friction between anecdotal and evidence-based teachings in
      osteopathic education in Europe.
AB  - Despite a growing interest in research and the implementation of standards for
      osteopathic education and practice in Europe, the inter-professional dialogue
      remains insubstantial. This article calls attention to the continuous challenges
      of reconciling anecdotal and evidence-based perspectives and offers suggestions
      on how to address these areas further.

PMID- 30100277
TI  - Multifidus muscle size changes at different directions of head and neck movements
      in females with unilateral chronic non-specific neck pain and healthy subjects
      using ultrasonography.
AB  - OBJECTIVE: The aim of the study was to compare the dimensions of cervical
      multifidus muscle (CMM) in different conditions. METHODS: Twenty five women with
      neck pain and 25 healthy subjects participated in this study. The dimensions of
      the CMM were measured at rest, 50% and 100% maximum isometric voluntary
      contraction (MIVC) at six directions of neck movements, using ultrasonography.
      RESULTS: The size of multifidus was smaller in patients than healthy individuals
      at rest state (P < 0.05). A significant smaller CMM dimension was found in the
      affected side compared with unaffected side in patients group (P < 0.05). The
      result of ANOVA for MLD showed a significant difference for contraction levels (P
      < 0.001) and neck movements (P < 0.001) in both groups. The MLD of the CMM was
      significantly different between CMM at rest and 50%, and 100% MIVC (P < 0.001).
      No significant differences were found between the groups at 50% and 100% MIVC (P
      > 0.05 in both instances). The most prominent CMM size change was observed during
      neck extension, flexion, ipsilateral lateral-flexion, and ipsilateral rotation,
      respectively (P < 0.05). CONCLUSIONS: Results of the present study indicate that
      the size of CMM was decreased in patients with neck pain in rest state. The size
      of CMM changes in all directions of neck movements, although the most prominent
      was during neck extension. This points out CMM stabilization role's in different
      directions of neck movements.

PMID- 30100278
TI  - Comparison between the Ki-hap technique and verbal encouragement on activation of
      abdominal muscles in healthy participants.
AB  - The aim of this study was to investigate the comparison between a Ki-hap, defined
      as a psyching-up technique, and verbal encouragement, defined as a verbal command
      by a third party, on abdominal muscle activation during performance of the crunch
      exercise in healthy participants. Ninety participants were randomly allocated to
      the following three groups: crunch only exercise group (CG, n1 = 30), crunch
      exercise with Ki-hap group (CKG, n2 = 30), and crunch exercise with Ki-hap and
      verbal encouragement group (CKVG, n3 = 30). The interventions were conducted over
      three trials with each group, and measurements involving each participant, were
      performed by a single examiner. The activation of the rectus abdominis (RA),
      external oblique (EO), and internal oblique (IO) muscles were evaluated using
      electromyography (EMG) during performance of the crunch exercise by the CG, CKG,
      and CKVG. Our results showed a significantly greater increase in the EMG patterns
      of all muscles during performance of the crunch exercise in the CKG (p < 0.05)
      compared to those in the CG and CKVG. The results also showed that there was a
      significantly greater increase in the activation of the EO and IO muscles in the
      CKVG (p < 0.05) compared with that in the CG. These findings demonstrated that
      the addition of the Ki-hap technique and verbal encouragement, during performance
      of the crunch exercise, improves activation of the abdominal muscles.

PMID- 30100279
TI  - Immediate effects of Maitland mobilization versus Mulligan Mobilization with
      Movement in Osteoarthritis knee- A Randomized Crossover trial.
AB  - BACKGROUND: Maitland Mobilization or Mulligan Mobilization with Movement (MWM)
      approaches have been widely used clinically for pain relief and improving
      mobility in Osteoarthritis knee. However the experimental evidence supporting the
      usage of these mobilization techniques as sole interventions in management of
      Osteoarthritis knee is insufficient. OBJECTIVE: To determine from Maitland
      Mobilization and Mulligan MWM, which mobilization technique will be more
      effective in reducing pain and improving mobility and function in OA knee
      immediately after the intervention. STUDY DESIGN: Randomized Crossover trial.
      MATERIALS AND METHODS: 30 subjects with osteoarthritis knee were recruited and 15
      each were randomly allocated to two intervention sequences-one sequence was where
      Maitland was given first followed by Mulligan and the other was where Mulligan
      was given first followed by Maitland with a washout period of 48 h in between the
      two interventions. Numeric Pain Rating Scale (NPRS), Timed Up and Go (TUG) test
      and Pain free Squat Angle were the outcome measures measured before and
      immediately after both interventions. RESULTS: Using Repeated Measures ANOVA for
      analysis of outcomes between and within interventions, no significant differences
      were seen between Maitland Mobilization and Mulligan MWM, for NPRS, TUG and Pain
      free Squat Angle (p = 0.18, p = 0.27,p = 0.17) respectively whereas within the
      interventions both Maitland and Mulligan all outcome measures showed significant
      changes (p < 0.001). CONCLUSION: Thus it can be seen that Maitland mobilization
      and Mulligan MWM, both are equally effective in osteoarthritis knee in reducing
      pain and improving functional mobility and pain free squat angle immediately post
      treatment.

PMID- 30100280
TI  - Scapular muscles' activity in female volleyball players with scapular asymmetry
      in the resting position.
AB  - BACKGROUND/AIM: Resting scapular asymmetry with a more protracted and depressed
      position of the scapula in the dominant throwing side relative to the scapula of
      the contralateral side is commonly detected in overhead athletes with both
      healthy and disabled shoulders. It has been proposed that possible alterations in
      the EMG activity of periscapular muscles due to asymmetric position of the
      scapula may alter its kinematics leading to shoulder pathology. The aim of the
      current study was to identify possible alterations in the activation of
      periscapular muscles of healthy female volleyball players with scapular asymmetry
      in the resting position. METHODS: Resting position of the scapula was determined
      in 37 healthy professional female volleyball players. Twenty-two players, with
      the scapula of the dominant side in a more protracted and depressed position
      compared to the non-dominant side, were classified as the asymmetry group.
      Fifteen players with almost symmetrical position of both scapulae comprised the
      control group. All participants performed an upper extremity closed chain
      exercise (knee push-ups) on a stable (floor) and an unstable surface (BOSU
      platform), while the EMG activity of serratus anterior (SA), upper trapezius (UT)
      and middle trapezius (MT) was recorded bilaterally. RESULTS: No significant group
      (asymmetry vs. control) by side (dominant vs. non-dominant) by surface condition
      (floor vs. BOSU platform) interaction was detected with regard to the EMG
      activity of SA, UT and MT. Although not statistically significant the asymmetry
      group demonstrated a tendency for reduced EMG activity of the SA on the dominant
      compared to the contra-lateral side and compared to the dominant side of the
      control group. CONCLUSIONS: The EMG activity of periscapular muscles (SA, UT and
      MT) was not affected during execution of a close chain exercise in healthy female
      volleyball players with the scapula of the dominant side in a more protracted and
      depressed resting position.

PMID- 30100281
TI  - Estimating bone mineral content based on different types of muscle strength
      tests.
AB  - The aims of this pilot study were to verify which muscle strength tests better
      explain bone mineral content (BMC) of the femoral neck and lumbar spine and to
      develop predictive equations to estimate femoral neck and lumbar spine BMC.
      Twenty-nine subjects aged 56-76 years old (12 women and 17 men) participated in
      the study. Femoral neck and lumbar spine BMC was evaluated by Dual X-ray
      absorptiometry (DXA). Muscle strength measurements included maximal isometric
      voluntary contractions of knee extensors and flexors, vertical jump, 5-repetition
      maximum of the leg press (5-RMLP) and seated leg curl (5-RMLC), and handgrip
      strength. Women presented a moderate to strong correlation between femoral neck
      BMC and 5-RMLP (r = 0.819), 5-RMLC (r = 0.879), knee extensors peak torque (r =
      0.699), and handgrip strength (r = 0.663), as well as between lumbar spine BMC
      and the 5-RMLP test (r = 0.845) and manual grip strength (r = 0.699). For
      females, the 5-RMLP and 5-RMLC tests most fully explained femoral neck BMC (R2 =
      0.859) and the 5-RMLP test and body mass explained lumbar spine density (R2 =
      0.757) for females. Men did not present correlations between BMC and strength
      variables. For females, the 5-RMLP and 5-RMLC variables explained the variations
      of femoral neck BMC, while 5-RMLP and body mass explained lumbar spine BMC.
      Future studies should evaluate a larger sample size and prioritize the strength
      tests with a greater predictive capacity.

PMID- 30100282
TI  - Leg press exercise can reduce functional hamstring:quadriceps ratio in the
      elderly.
AB  - The aim of this study was to investigate whether 12 weeks of leg press strength
      training exercise could affect the conventional and functional
      hamstring:quadriceps ratios in the elderly. Twelve elderly participants were
      submitted to a 12 week progressive training protocol (two sessions/week) using a
      45 degrees  leg press exercise. A significant increase in the one repetition
      maximum was observed after 4, 8, and 12 weeks (p = 0.001, p < 0.001, and p <
      0.001, respectively) compared to week 0 and after 8 (p = 0.011) and 12 weeks (p =
      0.001) compared to week 4. The concentric knee extensor peak torque was
      significantly higher at weeks 8 (p = 0.001) and 12 (p = 0.024) compared to week
      0. There was no change in the concentric and eccentric knee flexor peak torques
      (p = 0.629 and 0.274, respectively) and conventional ratio (p > 0.314) after 12
      weeks of training. The functional ratio (eccentric knee flexor peak
      torque:concentric knee extensor peak torque) reduced significantly after 8 (p =
      0.034) and 12 (p = 0.036) weeks of strength training. Although the 45 degrees 
      leg press exercise requires knee extensor and flexor, hip extensor, and plantar
      flexor muscle strength, our findings suggest that the isolated use of the 45
      degrees  leg press exercise reduces the knee functional ratio after 8 weeks of
      training. Therefore, 45 degrees  leg press exercise alone, without a hamstring
      exercise, should not be recommended for elderly individuals.

PMID- 30100283
TI  - The late effect of Kinesio Taping(r) on handgrip strength.
AB  - Kinesio Taping(r) elastic tape is increasingly used in physiotherapy treatment.
      However, there is a lack of scientific research regarding the late effects of its
      use. This study quantified the late effects of applying the Kinesio Taping(r)
      elastic tape by measuring changes in handgrip muscle strength after 24, 48 and 72
      h of application. The Kinesio Taping(r) elastic tape was applied on the dominant
      and non-dominant limbs of 36 volunteers randomly assigned to three groups: muscle
      facilitation, muscle inhibition and control group. The statistical test showed
      there was a statistically significant difference among all groups of dominant
      limb and non-dominant limb. However, the analysis on intragroup relationship to
      periods of application (Initial, 24, 48 and 72 h) and the interaction among
      repeated measures showed there was no statistically significant difference. This
      result may contribute to the investigation of the late effects of the Kinesio
      Taping(r) elastic tape on the physical rehabilitation.

PMID- 30100285
TI  - The amount of postural change experienced by adolescent computer users developing
      seated -related upper quadrant musculoskeletal pain.
AB  - BACKGROUND: Improved techniques of measuring sitting posture have not led to a
      more comprehensive understanding of poor posture, nor its association with pain.
      There is also an evidence gap regarding critical thresholds of sitting postural
      change over time related to pain production. This paper describes postural angle
      changes over a 12-month period, and describes the process of placing defensible
      cut-points in the angle change data, to better understand associations between
      posture change over time, and onset of upper quadrant musculoskeletal pain
      (UQMP). METHODS: This paper reports on data captured at baseline and 12-month
      follow-up, in adolescents in school using computers. Four sitting postural
      angles, head flexion (HF), neck flexion (NF), craniocervical angle (CCA) and
      trunk flexion (TF), and self-reported seated UQMP in the previous month were
      captured at each time-point. Research questions were: 1) What is the magnitude
      and direction of change in each postural angle over 12 months? 2) What are best
      cut-points in the continuous posture change distribution to most sensitively test
      the association between posture change and UQMP? 3) Is gender-specific cut-points
      required? The 12-month posture angle change data was divided into quintiles (0
      20th%; 21-40th%, 41-60th%, 61-80th%, >80th%), and the odds of UQMP occurring in
      each posture change quintile were calculated using logistic regression models.
      RESULTS: Two hundred and eleven students participated at baseline, of which 153
      were followed-up at one year. Both males and females with postural change into
      extension (which represents lesser flexion range) were more at risk for the
      development of UQMP, than any other group. The best cut-point for HF was 40th%
      (<=-3.9 degrees ), NF was 20th% (<=-2.9 degrees ) and TF was 40th% (<=-1.1
      degrees ). For CCA however, change at or beyond 40th % for extension or beyond
      60% for flexion was associated with UQMP. CONCLUSIONS: Identification of critical
      postural angle change cut-points assists in considering the pain-producing
      mechanisms for adolescents using desk top computers.

PMID- 30100284
TI  - The comparison of pinch strength among female typists and female non-typists.
AB  - BACKGROUND: Typing is a common activity involving repetitive motion that can
      increase the risk of work-related injuries. To the best of our knowledge, the
      effect of typing on the pinch strength has not been investigated so far.
      OBJECTIVE: To investigate the pinch strength amongst female typists and non
      typists. METHOD: Thirty female typists and 30 female non-typists, aged 20-30
      years old, participated in this prospective study. The pinch strength of the
      second, third, fourth and fifth fingers of the dominant hand was measured in a
      sitting position, using a pinch gauge. The data were analyzed using independent
      sample t-test. RESULTS: The results showed that there were significant
      differences in the pinch strength of the second, third and fourth fingers between
      the two groups. The strength of these fingers was reduced more than that in
      female non-typists. CONCLUSION: Our results suggest that pinch strength might
      have decreased in female typists due to sharing common attentional resources,
      muscle fiber composition, and muscle fiber fatigue.

PMID- 30100286
TI  - Acute effects of whole body vibration on heart rate variability in elderly
      people.
AB  - BACKGROUND: Whole body vibration (WBV) has been widely used as a modality for
      physical activity. In fact, WBV has been used for physical rehabilitation, and to
      improve muscle performance; but there is little information about its effects on
      heart rate variability (HRV). AIM: The aim of this study was to evaluate the
      effect of vibration on HRV of the elderly using the vibratory platform. METHODS:
      Eleven older adults (7 men, 4 women), aged between 60 and 75 years, were
      subjected to WBV. The study consisted of a single session of WBV with volunteers
      standing upright for 10 min on the oscillating platform, with frequency of
      vibration set at 20 Hz (displacement +/- 6 mm; orbital vibration). Pre (baseline)
      and post-WBV electrocardiograph signals were acquired using a cardiac monitor;
      and data were statistically analyzed using paired Student's t-test or Wilcoxon
      test, as appropriate. RESULTS: The results demonstrated an increase in SDNN
      (standard deviation (SD) beat-to-beat, N-N intervals), rMSSD (square root of the
      mean squared difference of successive N-Ns) and pNN50 (proportion of N-N50
      divided by total number of N-Ns) post WBV (p = 0.032, p = 0.024 e p = 0.044,
      respectively), compared to baseline. The present study thus demonstrated that
      time domain variables (i.e., SDNN, rMSSD, and pNN50) increase post WBV.
      CONCLUSIONS: Older individuals are at high risk of developing cardiovascular
      diseases. As seen in the study, WBV improves HRV; and may help reduce risk of
      cardiac ailments. Moreover, WBV does not require extensive physical activity on
      the part of the participant. This makes WBV potentially beneficial to the elderly
      population. Further studies on WBV using different frequencies and training
      schedules may improve its applicability in clinics.

PMID- 30100287
TI  - Energy efficiency of ambulation-A comparison of various orthopaedic
      possibilities.
AB  - BACKGROUND: In most developing countries, accessibility for people using walking
      aids is limited due to architectural and environmental barriers. As observed from
      anecdotal accounts, even a minor orthopaedic injury/disorder may restrict a
      person's ambulation due to fatigue associated with using walking aids. Hence this
      study was undertaken with the following objective. OBJECTIVE: to estimate the
      magnitude of energy consumption using energy expenditure index (EEI) during gait
      under different conditions. DESIGN: Repeated measures design (within subjects
      study). SETTING: School. PARTICIPANTS: Ten healthy, typical young adults between
      17 and 25 years of age. OUTCOME MEASURE: Energy Expenditure Index (EEI) was
      estimated for each of the conditions of the study using consistent measurement
      procedures. RESULTS: Energy consumption with immobilization is greater (ankle
      16.2%, knee-36.7% and ankle and knee-49.2%) than typical self-selected
      ambulation. During on ground ambulation the energy cost was greatest for an
      axillary crutches than a standard walker with ankle and knee immobilized being
      the highest in relation to typical ambulation (78.2% greater). Axillary crutches
      were more efficient than a walker during stair climbing. CONCLUSION: For young
      adults a standard walker may be the right option for over-ground ambulation, when
      a lower limb joint in immobilized; with an axillary crutch used during stair
      climbing.

PMID- 30100288
TI  - Automatic activity of deep and superficial abdominal muscles during stable and
      unstable sitting positions in individuals with chronic low back pain.
AB  - OBJECTIVE: The purpose of this study was to assess muscle thickness changes in
      the deep and superficial abdominal muscles, during sitting on stable and unstable
      surfaces in subjects with and without chronic low back pain (CLBP). METHOD: A
      cross-sectional study was conducted involving 40 participants (20 CLBP and 20
      healthy). Ultrasound imaging was used to assess changes in the thickness of the
      Transversus abdominis (TrA), Internal Oblique (IO), Rectus abdominis (RA) and
      External oblique (EO) muscles. Muscle thickness under two different sitting
      postures; (sitting on a chair and sitting on a Swiss ball), was normalized to
      actual muscle thickness at rest in the supine lying position and was expressed as
      a percentage of thickness change of muscles. RESULT: The results showed
      significantly greater thickness changes in RA muscle in the CLBP patients
      compared to the healthy subjects, during both stable and unstable sitting
      positions. Also, significantly lower thickness changes in TrA muscle was observed
      in subjects with CLBP compared to those without CLBP, during unstable sitting
      position. CONCLUSION: There was an imbalance between the automatic activity of
      TrA and RA muscles in the subjects with CLBP, compared to the pain-free controls,
      during an unstable sitting position. Therefore, it is necessary to pay attention,
      to the altered automatic activity of the abdominal muscles while utilizing a
      Swiss ball, for rehabilitation of subjects with CLBP.

PMID- 30100289
TI  - The effects of task execution variables on resultant vertical ground reaction
      force acting on foot sole during squat lifting.
AB  - The main objective of this study was to investigate the effects of task execution
      variables on the value and point of application of the resultant vertical ground
      reaction force acting on the foot sole during squat lifting. This can be of
      particular importance since it may help to recognize the roles of the foot sole
      parts in bearing the support force during industrial and labor lifting
      activities. Twelve healthy men lifted a box with 4, 8 and 12 kg masses at fast
      and slow speeds. Ground reaction force and center of pressure were measured using
      two parallel Kistler force-plates. In addition, a Vicon system and a 3D linked
      segment model were used to define the movement pattern. Significant increases
      resulted for the peak vertical ground reaction force with the increases in the
      lift speed (P < 0.05) and box weight (P < 0.05). As well a significant increase
      resulted for the range of center of pressure location with the increase in the
      box weight (P < 0.05). Moreover, significant interactions (P < 0.05) between the
      lift speed and box weight were detected. The front and rear parts of the foot had
      the most important roles in bearing the support force during the beginning and
      final phases of movement, respectively. Finally, it was concluded that the value
      and point of application of vertical ground reaction force are seemingly
      dependent on the momentum of the subject plus box.

PMID- 30100290
TI  - Type effect of inhibitory KT tape on measured vs. perceived maximal grip
      strength.
AB  - This study examined the effects of KT tape (KT) applied in an inhibitory manner
      on muscle activity, measured maximal grip strength, and perceived maximal grip
      strength in regular KT-users and non-users. This study was a single-blinded
      crossover study with sixty participants including 27 kT-users and 33 non-users.
      Participants underwent maximal grip strength tests with and without inhibitory KT
      applied across the wrist extensors. Muscle activity and maximal grip strength
      were measured, while perceived maximal grip strength was rated using a visual
      analogue scale. No significant interaction effect was found between taping
      conditions and participant KT-experience for muscle activity (F = 0.825, p =
      0.367), measured grip strength (F = 1.018, p = 0.317) or perceived grip strength
      (F = 0.122, p = 0.728). No significant differences were observed in the EMG
      activity between taping conditions for either KT-users (p = 0.367) or non-users
      (p = 0.215). A similar trend was found in the measured grip strength (KT-users: p
      = 0.317; non-users: p = 0.294) and perceived grip strength (KT-users: p = 0.728;
      non-users: p = 0.063). KT applied in an inhibitory manner does not impede EMG
      activity, measured maximal grip strength, or perceived maximal grip strength in
      adults, regardless of their preconceived notions of KT.

PMID- 30100291
TI  - An ultrasonographic investigation of deep neck flexor muscles cross-sectional
      area in forward and normal head posture.
AB  - BACKGROUND: As one of the most common work-related musculoskeletal disorders and
      postural deviations, forward head posture (FHP), is considered to lead to muscle
      imbalance. OBJECTIVES: The aim of this study is to investigate the bilateral
      cross-sectional area (CSA) of the deep neck flexor muscles at rest and during
      five stages of the craniocervical flexion (CCF) test in individuals with FHP and
      the controls with normal head posture. METHODS: Eighteen students with FHP and 18
      controls with normal head posture, all females aged 18-35 years, participated in
      this study. Participants were categorized into two groups based on their
      craniovertebral angle. The CSA of the deep neck flexors was measured using
      ultrasonography while participants lay supine on the table with a pressure
      biofeedback unit placed under their necks in order to let the examiner measure
      the CSA of the muscles during rest and five stages of the CCF test including 22,
      24, 26, 28, and 30 mmHg of the pressure biofeedback unit. RESULTS: A significant
      effect of contraction level was observed in both groups, indicating significant
      increases of the CSA of the deep neck flexors during contraction (F = 64.37, P <
      0.001). No significant difference was evident for the CSA of the deep neck
      flexors between the groups, although the increase in the CSA of the deep neck
      flexors was up to 28 mmHg in the normal head posture group compared to 26 mmHg in
      the FHP group. CONCLUSIONS: The results of the present study showed no
      significant difference between the performance of the deep neck flexors during
      the CCF test in FHP and normal head posture individuals, which challenge the
      common belief of the deep neck flexors weakness in individuals sustaining FHP.

PMID- 30100292
TI  - Integration of a neurodynamic approach into the treatment of dysarthria for
      patients with idiopathic Parkinson's disease: A pilot study.
AB  - PURPOSE: Differences between standard dysarthria treatment and the same treatment
      with the integration of neurodynamic techniques tailored to the severity of
      dysarthria in patients with Parkinson's disease were examined. METHOD: In total,
      10 subjects with idiopathic Parkinson's disease and rigid-hypokinetic dysarthria
      were enrolled in this quasi-randomized, controlled, single-blind, pre-post study.
      In each of 12 therapy sessions the control group (n = 5) received standard
      dysarthria treatment (usual care), while the intervention group (n = 5) received
      the same treatment with the addition of integrated neurodynamic treatment
      (special care). RESULTS: There was no significant difference between the two
      groups for either the pre-test (p = 0.739) or the post-test (p = 0.156) results.
      However, significant differences between the pre-test and post-test results
      within each group (intervention group p = 0.001; control group p = 0.003) were
      found. CONCLUSIONS: The significant differences in the pre-post comparison within
      the groups may indicate a high probability of a positive effect of standard
      dysarthria treatment on the severity of dysarthria. In between-group comparisons,
      the study results indicated no evidence of a significant difference between
      standard dysarthria treatment with or without neurodynamics. Due to the small
      sample size, the effectiveness of the integration of neurodynamics into speech
      therapy cannot be definitively concluded for now. In order to be able to have
      generalized applicability, future studies with larger numbers of participants are
      required.

PMID- 30100293
TI  - Muscle thickness and echo intensity measurements of the rectus femoris muscle of
      healthy subjects: Intra and interrater reliability of transducer tilt during
      ultrasound.
AB  - : This study aimed to assess the intra and interrater reliability of transducer
      tilt during the ultrasound (US) measurements of the muscle thickness and the echo
      intensity of the rectus femoris muscle (RF). Fourteen healthy male subjects (20.8
      +/- 0.8 years) participated in this study. The transducer tilt was measured using
      a digital angle gauge ( degrees ) during US. Two experimenters took two images to
      measure the muscle thickness (mm) and the echo intensity (a.u.: arbitrary unit).
      The intra and interclass correlation coefficient (ICC), standard error of
      measurement (SEM), and minimal detectable change (MDC) were also calculated.
      These measurements were immediately repeated. The ICC for the intrarater
      reliability for the transducer tilt, muscle thickness, and echo intensity were
      0.96 (SEM: 0.9 degrees , MDC: 2.6 degrees ), 0.99 (SEM: 0.4 mm, MDC: 0.1 mm), and
      0.97 (SEM: 0.6 a.u. , MDC: 1.7 a.u.), respectively. The ICC for the interrater
      reliability for the transducer tilt, muscle thickness, and echo intensity were
      0.40 (SEM: 4.0 degrees , MDC: 11.1 degrees ), 0.96 (SEM: 0.7 mm, MDC: 2.0 mm),
      and 0.95 (SEM: 0.9 a.u. , MDC: 2.4 a.u.), respectively. The intrarater
      reliability of the transducer tilt was reliable, but the interrater reliability
      was questionable. Meanwhile, both the intra- and interrater reliability of the
      muscle thickness and the echo intensity were reliable.

PMID- 30100294
TI  - A comparison of foot kinetic parameters between pronated and normal foot
      structures during forward jump landing.
AB  - BACKGROUND: Pronated foot is one of the most important factors that may lead to
      musculoskeletal injuries of the lower extremities. It is known that in a pronated
      foot, excessive mechanical loads are applied to the lower limb structures, which
      result in the altered foot biomechanics, including vertical ground reaction
      forces (VGRFs) and rate of loading (ROL). Therefore, the aim of this study was to
      determine the changes in foot kinetic parameters in the pronated compared to the
      normal foot structures. METHODS: In this cross-sectional study, 15 individuals
      (mean age of 23.27 +/- 3.28 years) with asymptomatic pronated feet and 15 normal
      subjects (mean age of 23.40 +/- 3.11 years) were recruited from both genders by
      using a simple non-random sampling method. VGRF, ROL, and the resultant vector of
      time to stabilization (RVTTS) were evaluated during the forward jump landing task
      by using a force plate. RESULTS: The findings showed that the following
      parameters were significantly higher in the group of pronated feet than in the
      normal subjects: VGRF (3.30 +/- 0.17 vs. 2.81 +/- 0.15, p = .042), ROL (0.10 +/-
      0.01 vs. 0.07 +/- 0.006, p = .020), and RVTTS (2592.80 +/- 141.24 vs. 2114.00 +/-
      154.77, p = .030). CONCLUSION: All the measured foot kinetic parameters were
      higher in the pronated foot subjects than in the normal participants. An impaired
      movement control and greater forces imposed on the foot region of the pronated
      foot, compared to the normal foot individuals, were discovered indicating the
      former group's possible increase of susceptibility to various musculoskeletal
      injuries.

PMID- 30100295
TI  - Cardiac autonomic response after cranial technique of the fourth ventricle (cv4)
      compression in systemic hypertensive subjects.
AB  - OBJECTIVE: The aim of this study was to compare blood pressure (BP) behavior and
      heart rate variability (HRV) among hypertensive stage I and normotensive
      individuals who were submitted to the cranial technique of the 4th ventricle
      compression (CV4), an osteopathic technique. METHODS: In this experimental
      controlled study, thirty men between 40 and 60 years old were evaluated and
      divided into two groups: normotensive (NT) and hypertensive (HT). The CV4
      maneuver was applied in both groups and BP was measured at 5 (five) different
      stages: pre and post-intervention, 5, 10 and 15min after technique. Time
      frequency parameters were obtained from measurements of RR intervals. Data were
      analyzed using an ANOVA two-way for analysis of the condition factor (NT and HT)
      and times with p-value <= .05. RESULTS: There was a reduction in the BP of the HT
      group. A significant intergroup difference (p = .01) was noticed, with respect to
      the standard deviation of successive normal R-R intervals (SDNN) values, mainly
      between pre-intervention and 15min stages. Concerning root mean square of the
      mean squared differences (RNSSD) values, the highlights were differences between
      pre-intervention and 10min (p = .01) only in the NT group. There was an increase
      in high frequencies (HF) values and a low frequencies (LF) attenuation in both
      groups at all different stages. CONCLUSION: The data showed a BP reduction in the
      HT group in pre-intervention/15min and an increase in parasympathetic activity
      and decreased sympathetic activity in both groups. This suggests a change in the
      sympathetic-vagal balance. However, further studies are needed to elucidate the
      data on BP reduction mechanisms with CV4.

PMID- 30100296
TI  - A critical overview of the current myofascial pain literature - July 2018.
AB  - In the current issue of this clinical overview, we are pleased to include several
      basic research studies ranging from the differentiation of radicular and non
      radicular low back pain based on the presence of trigger points (TrPs) to the
      role of TrPs in patients with osteoarthritis, the diagnostic criteria of TrP, the
      accurate placement of needles in the piriformis muscle with dry needling (DN),
      and the reliability of TrP identification, among others. As usual, there are many
      new DN studies, but also several review papers, and manual TrP research.
      Contributing authors come from as many as 15 different countries!

PMID- 30100297
TI  - Comprehensive treatment for patients with chronic pain in a 12-step based
      substance use disorder program.
AB  - Patients with chronic pain (CP) and substance use disorder (SUD) are complex, not
      yet adequately described, and in need of comprehensive treatments that address
      both diseases concurrently. Our objectives were to (a) describe a cohort of CP
      patients who failed traditional treatment (mainly opioids) - then developed
      opioid use disorder (OUD) and other SUDs and (b) evaluate a comprehensive
      inpatient treatment program for these patients. Patients were enrolled in an
      inpatient CP program. Treatment consisted of medical detoxification, group
      process/education, external and internal qigong, osteopathic manual medicine, and
      qigong-based mindfulness. Patients also received 20 h per week of 12-step
      recovery-based SUD treatment. Patients were evaluated at the beginning of
      treatment (first assessment, day 1-5 range) and at days 30 and 45. Assessments
      were: Beck Depression Inventory-II, Brief Pain Inventory, West Haven-Yale
      Multidimensional Pain Inventory (patient section), and McGill Pain Questionnaire.
      The Global Impression of Change Scale was administered at day 45. A mixed model
      analysis was used to evaluate treatment progress. Demographic data revealed an
      older cohort with OUD, other SUDs, and multiple pain diagnoses who failed
      traditional treatment. Questionnaire evaluations were consistent and similar
      across all of the above measures: patients' scores showed marked, statistically
      significant improvements in depression, pain, and quality of life ratings. The
      most substantial improvements occurred between the first and second assessments.
      The findings are sufficiently encouraging to warrant further evaluation of the
      protocol and to plan comparative studies.

PMID- 30100298
TI  - No immediate analgesic effect of diadynamic current in patients with nonspecific
      low back pain in comparison to TENS.
AB  - BACKGROUND AND DESIGN: Chronic nonspecific low back pain (CNSLBP) has major
      socioeconomic as well as personal impact in many industrialized and developing
      countries. Physiotherapy is a common intervention for this group of patients and
      using anti-pain physical modalities is a common part of the physical therapy. In
      a randomized controlled trial we investigated the immediate effect of the
      Diadynamic current in comparison to TENS on reducing the pain in patients
      suffering from non specific chronic low back pain. METHODS: Thirty patients were
      randomized into the Diadynamic current and TENS groups. Electrical stimulation
      was applied for 10 min in the Diadynamic group and for 15 min in the TENS group
      for one session. Pain, on a 100 mm Visual Analog Scale, and Pressure Pain
      Threshold (PPT), using an Algometer, was measured before the treatment, after the
      current application, 20 min later and after 48 h. RESULTS: Pain was decreased
      significantly after 20 min following the current application only in the TENS
      group, with no improvement at all measurement points in the group receiving
      Diadynamic current. PPT was increased immediately after current application in
      both groups but did not last until later measurements. CONCLUSION: Diadynamic
      current had no positive effect on prompt relief of pain in patients suffering
      from recurrent CNSLBP.

PMID- 30100299
TI  - Short-term effects of kinesio taping on trigger points in upper trapezius and
      gastrocnemius muscles.
AB  - BACKGROUND: Kinesio taping is a possible therapeutic modality for myofascial
      pain, nevertheless, very scarce research has been performed on this subject.
      OBJECTIVE: To evaluate the immediate and short-term effect of kinesio taping
      application on myofascial trigger points (MTrPs) and pressure pain thresholds
      (PPTs) in the upper trapezius and gastrocnemius muscles. METHODS: Two randomized,
      single-blinded, controlled trials were simultaneously executed on the upper
      trapezius and gastrocnemius muscles. Different participants in each study were
      randomly assigned to an active intervention (N = 15) or control (N = 15) group.
      Kinesio taping was applied on the gastrocnemius or upper trapezius muscles by
      positioning three "I" strips in a star shape (tension on base) directly above the
      MTrPs in the active intervention group and a few centimeters away from the MTrPs
      in the controls. RESULTS: The second evaluation on both sides showed lower PPT
      values than the first evaluation in the control group, denoting that the spots
      were more sensitive. The third evaluation showed even lower values. The active
      intervention group showed a contralateral side pattern similar to the controls.
      However, on the side of the kinesio taping application, the PPT values of the
      second evaluation were higher (the spots were less sensitive) and after 24 h
      returned to the original values. The difference between the PPT measurements on
      the MTrPs' side of the active intervention group vs. the controls (time-group
      interaction) was significant (F (2,56) = 3.24, p = 0.047). CONCLUSIONS: We
      demonstrated that a kinesio taping application positioned directly above the
      MTrPs may prevent an increase in sensitivity (decrease in PPT) immediately after
      application and prevent further sensitization up to 24 h later. The fact that two
      different muscles were similarly affected by the kinesio taping application,
      confirmed that the results were not in error. Further studies are needed to
      directly test the effect of a kinesio taping application on post-treatment
      soreness.

PMID- 30100300
TI  - Comparison of a foam rolling session with active joint motion and without joint
      motion: A randomized controlled trial.
AB  - BACKGROUND: Foam rolling has become a popular form of self-myofascial release or
      roller massage among health and fitness professionals. Due to this popularity,
      foam roller devices can be found in many clinical and fitness settings. Despite
      the popularity, there are still several unknowns regarding foam rolling such the
      optimal technique. Specifically, there is a lack of research analyzing different
      foam roll techniques such as combining active joint motion with foam rolling.
      PURPOSE: The purpose of this study was to compare the effects of a foam rolling
      session to the left quadriceps with active joint motion and without joint motion
      on passive knee flexion range of motion (ROM) and pressure pain thresholds (PPT).
      METHODS: Thirty healthy adults were randomly allocated to one of two intervention
      groups: active joint motion and no joint motion. Each foam roll intervention to
      the left quadriceps lasted a total of 2 min. Dependent variables included passive
      knee flexion ROM and pressure pain threshold measures (PPT). Statistical analysis
      included subject demographic calculations and appropriate parametric and non
      parametric tests to measure changes within and between intervention groups.
      RESULTS: For left knee ROM, the active joint motion group demonstrated the
      greatest immediate increase in passive ROM (8 degrees , p < .001) than the non
      motion group (5 degrees , p < .001). For PPT, the active joint motion group
      demonstrated the greatest immediate increase (180 kPa, p < .001) followed by the
      non-motion group (133 kPa, p < .001). Between group comparisons revealed a
      significance between groups for passive knee ROM (p < .001) and PPT (p < .001).
      CONCLUSION: A short session of foam rolling with active joint motion appears to
      have a greater effect on passive joint ROM and PPT than rolling without motion.
      These observed changes may be influenced by the agonistic muscle activity during
      active motion. This activity may modulate activity of the antagonist muscle
      through reciprocal inhibition and other neural pathways. Future research is
      needed to confirm these findings.

PMID- 30100301
TI  - Knowledge of self-myofascial release among allied health students in the United
      States: A descriptive survey.
AB  - BACKGROUND: University and collegiate education of the human myofascial system is
      commonly taught in basic science courses such as anatomy. Allied health programs
      may expand upon these concepts by teaching interventions such as myofascial
      release in clinical education courses. Self-myofascial release (SMR) with a
      device such as a foam roller is an emerging intervention that has become popular
      among clinicians and active individuals. Currently, it's unknown if allied health
      programs provide SMR education. PURPOSE: The purpose of this study was to survey
      and document responses in the knowledge of SMR among allied health students.
      METHODS: 12 undergraduate and graduate allied health programs in the United
      States were sent a 12-question electronic survey that represented three areas: 1)
      respondent demographics and beliefs, 2) experience with SMR, 3) future practice
      and education. Descriptive data including response frequency and percentage was
      calculated and reported for the 12 questions. RESULTS: A total of 502 students
      from the different allied health programs completed the survey which represented
      a 33.00% response rate (502/1521). Approximately, half of respondents (49.6%, N =
      249) reported learning about SMR in their degree program and the other half
      (50.40%, N = 253) report receiving no education. Most respondents (>50%)
      currently use or have used an SMR device and believe that SMR produces
      therapeutic benefits. Furthermore, most respondents (>=50%) had an idea of how
      they would integrate SMR into their future practice and where to purchase an SMR
      device. CONCLUSION: A more global consensus on education for emerging therapeutic
      intervention such as SMR is needed in order to standardize and develop best
      teaching practices in allied health. This study highlighted the difference among
      allied health programs in the United States. This research should be a starting
      point for future survey research on this topic.

PMID- 30100302
TI  - The use of electrodiagnostic studies and musculoskeletal sonography in carpal
      tunnel syndrome.

PMID- 30100303
TI  - Evaluation of integral electromyographic values and median power frequency values
      in women with myogenous temporomandibular disorder and asymptomatic controls.
AB  - BACKGROUND: Surface electromyography (EMG) has been used as a reliable tool for
      the evaluation of electrical muscle activity. OBJECTIVE: The purpose of this
      study was to evaluate the EMG indices of the masticatory muscles (masseter,
      anterior temporalis and suprahyoid) in women with temporomandibular disorder
      (TMD) and asymptomatic controls in the time domain, by the integrated EMG signal
      (IEMG) and in the frequency domain, using the median power frequency (MPF).
      METHODS: An observational, cross-sectional study was conducted involving 30
      asymptomatic women as the control (mean age: 25.85 +/- 2.57 years) and 74 women
      with myogenous TMD (mean age: 26.54 +/- 2.45 years) diagnosed using the Research
      Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Three EMG readings
      were taken during maximum voluntary clenching (MVC) of the molars on parafilm for
      five seconds with a three-minute rest interval between readings. The mixed-model
      analysis of variance test followed by the Bonferroni correction or the Student-t
      test was used for the analyses, with the level of significance set to 5% (p <
      0.05). RESULTS: IEMG values were significantly higher in the masseter muscles
      than the anterior temporalis muscles in the control group (p < 0.01). IEMG values
      were significantly higher in the masseter muscles of the control group than the
      group with myogenous TMD (p < 0.05). MPF values of the suprahyoid muscles were
      significantly higher in the myogenous TMD group than the control group.
      CONCLUSIONS: These significant findings show that women with myogenous TMD have
      reduction of electrical activity of their masseter muscles and increased firing
      rate of the motor units of the suprahyoid muscles. These findings may help the
      treatment of myogenous TMD in women.

PMID- 30100304
TI  - Does Kinesio taping correct exaggerated dynamic knee valgus? A randomized double
      blinded sham-controlled trial.
AB  - BACKGROUND: Deficiency in hip girdle neuromuscular control can cause exaggerated
      Dynamic Knee Valgus (DKV) which afflicts the knee joint and lead to knee injuries
      especially ACL injury in sports. Though Kinesio taping (KT) is known to improve
      function, stability and proprioception, the evidence is inconclusive on its
      effectiveness in athletes. We hypothesized that kinesio taping could enhance
      neuromuscular control of the hip girdle there by causing a reduction in DKV.
      AIM/OBJECTIVE: To determine whether KT on Gluteus medius can correct exaggerated
      dynamic knee valgus and improves hip abductor strength when compared to sham KT.
      METHOD: 40 collegiate level athletes, aged between 18 and 28 years, of both
      genders with presence of dynamic knee valgus (>8 degrees  for men and >13 degrees
      for women) were recruited in the study. Athletes were excluded if they had
      history of lower back pain, history of any injury or surgery to the lower
      extremities during the past year. Subjects who met the inclusion criteria were
      randomized into kinesio taping (KT) group and sham taping (ST) group. The Drop
      Jump test and the Donnatelli Drop Leg Test (DDT) were performed before, and on
      the third day, immediately after the application of KT on them and documented.
      RESULTS: There was a significant reduction in DKV among male [4.0 degrees  (95%
      CI 3.5-4.5); p < 0.001] and female [4.3 degrees  (95% CI 3.5-5.2); p < 0.002]
      immediately after application of taping but not on the third day after
      application of KT. There was a significant rise in DDT immediately and on the
      third day after application of KT between KT group and SC group. CONCLUSION:
      There was a reduction in DKV immediately after the application of KT. However,
      there was no significant difference between KT group and SC group on the third
      day. Meanwhile, gluteus medius strength also showed significant improvement
      immediately after taping and it was maintained even on the third day.

PMID- 30100305
TI  - Transabdominal ultrasound: Can it be used to detect and quantify
      adhesions/reported pain, following Caesarean section?
AB  - BACKGROUND: Caesarean section is common in the UK with post-procedural adhesions
      causing life-long clinical symptoms and impacting future pregnancies. This
      study's aim was to explore associations between these surgical adhesions, via
      transabdominal ultrasound findings, and perceived symptoms. METHOD: Females
      demonstrating 1-3 transverse, lower-segment Caesareans were included. Visceral
      slide transabdominal ultrasound elicited positive adhesions (<1 cm movement) and
      negative adhesions (>1 cm movement). Scar tissue quality was assessed by the
      Patient and Observer Scar Assessment Scale (POSAS) and Numerical rating scales
      (NRS) described pain symptoms. The relationship between adhesions was explored
      using Fisher's exact test and multiple regression analysis. RESULTS: Twenty-two
      subjects (mean-age 35) were recruited; twenty participants (91%) had undergone 1
      Caesarean, one each of the remainder had undergone 2 and 3 Caesareans
      respectively. Increased Visceral slide (>1 cm) was seen as predictive of
      increased scar pain (R2 = 0.76 (95% CI 0.12-0.28), P < 0.001). CONCLUSION:
      Caesarean adhesion scans showed significant associations with pain symptomology.
      Comprehensive adhesion assessment needs to be developed to improve long term
      outcomes of adhesions. Transabdominal Ultrasound can be considered a useful,
      quick and non-deleterious alternative diagnostic tool to Laparoscopy, therefore
      preventing further adhesion formation.

PMID- 30100306
TI  - Do different methods for measuring joint moment asymmetry give the same results?
AB  - Gait asymmetry is defined as a loss of perfect agreement between the dominant and
      non-dominant lower limbs. Conflicting results from gait asymmetry studies may be
      due to different definitions of asymmetry, different research methods, and/or
      different variables and formulas used for asymmetry calculation. As a result,
      this makes it difficult to compare joint asymmetry values between studies. An
      accurate and precise understanding of asymmetry during human walking is an
      important step towards developing enhanced rehabilitation protocols for
      pathological gait. This study examined bilateral lower extremity joint moment
      asymmetry during the stance phase of walking using three different methods.
      Fourteen male children (with flat feet) aged 8-14 years participated in this
      study. The three-dimensional lower limb kinetics was evaluated during a
      comfortable gait. Then, right and left lower limb joint moments were used to
      calculate the joint moment asymmetry via three different methods (Lathrop-Lambach
      method: equation used by Lathrop-Lambach et al. (2014); Su method: equation used
      by Su et al. (2015); Nigg method: equation used by Nigg et al. (2013)). Repeated
      measures ANOVAs (alpha = 0.05) were used to compare the values of net joint
      moment asymmetry calculated by the three methods. The results of the statistical
      analyses found that the amounts of moment symmetry between limbs calculated by
      the first two methods were significantly greater than that of using the Nigg
      method (except for the values of the frontal ankle moment computed by the Lathrop
      Lambach method). Furthermore, in comparison of the first two methods, using the
      Su method showed a reduction in moment asymmetry for all joints and for all
      moments (p < 0.05). We conclude that, although all of three common methods for
      determining asymmetry between limbs have documented merit, they sometimes differ
      dramatically in results.

PMID- 30100307
TI  - An examination of the relationship between dynamic knee joint stiffness and gait
      pattern of children with cerebral palsy.
AB  - Dynamic joint stiffness represents the resistance that a joint opposes to an
      applied moment. Stiffness arises in conditions of joint laxity, instability and
      increased co-contraction and is commonly utilized as a means to stabilize the
      joint. The knee joint seems to be crucial for determining the walking pattern.
      The aim of this study was to investigate the association between the gait
      pattern, globally quantified by the Gait Profile Score (GPS), which indicates the
      'quality' of a particular walking strategy, and knee dynamic joint stiffness (Kk)
      in children with diplegia. Kk is expressed by plotting the values of the knee
      flexion-extension moment versus the knee flexion-extension angle during weight
      acceptance. In this interval, the linear regression was fitted. The angular
      coefficient of the linear regression corresponded to the joint stiffness index.
      Sixty-one children with diplegia and 18 healthy individuals took part in this
      study. From their gait analysis data, the GPS (with its Gait Variable Scores
      GVSs) and the Kk were calculated. Data showed that GPS (p = 2.73 * 10-21) and
      GVSs values for the patients with diplegia were higher in comparison to healthy
      controls. The Kk values for patients were not statistically different from those
      of controls. The correlation between Kk and GPS did not show the presence of any
      significant relationship (r = -0.04; p > 0.05). Thus, the functional limitation
      in diplegic children does not seems to be strictly related to Kk.

PMID- 30100309
TI  - Association between hyper-pronated foot and the degree of severity of disability
      in patients with non-specific low back pain.
AB  - BACKGROUND: It has been established that Hyper-pronation of the foot may lead to
      postural changes in the lower limbs, with a resultant pelvic ante-version, and a
      subsequent risk of development of low back pain. However, the association between
      the presence of a hyper-pronated foot and the severity of disability in low back
      pain is currently not known. OBJECTIVES: The purpose of this study was to examine
      whether the presence of a hyper-pronated foot has any impact on the degree of
      severity of disability (functional status) in patients with non-specific low back
      pain. METHODS: An observational study was conducted in an outpatient setting,
      where patients diagnosed as having non-specific low back pain were included. The
      degree of severity of disability was measured using the Modified Oswestry Low
      Back Pain Disability Questionnaire, and the foot hyper-pronation was assessed
      with the execution of the Navicular Drop test. Descriptive statistics and Linear
      regression analyses were conducted. RESULTS: Of the 71 patients included, 14
      demonstrated having a unilateral hyper-pronation of the foot. The mean scores for
      the functional status and hyper-pronation of the foot were 37.15 (SD = 10.40) and
      6.06 (SD = 3.42) respectively. An association was not found between the severity
      of disability and the presence of foot hyper-pronation (B = .87, p = .78).
      CONCLUSIONS: Hyper-pronation of the foot could lead to the development of non
      specific low back pain, but the degree of severity of the disability is not
      influenced by the presence of a hyper-pronated foot. The alterations in lower
      limb mechanics leading to back pain are a complex issue, and thus needs further
      research.

PMID- 30100308
TI  - Thoracic hyperkyphosis non invasively measured by general practitioners is
      associated with chronic low back pain: A cross-sectional study of 1364 subjects.
AB  - OBJECTIVE: The aim of this study was to examine the association between trunk
      sagittal posture and nonspecific chronic low back pain (CLBP) by evaluating plumb
      line distances in subjects recruited in an everyday clinical setting. METHODS: Of
      the 1364 subjects recruited, 63.1% were female (mean age +/- SD: 56.2 +/- 16.8
      years). Subjects were categorized into CLBP and control groups and were
      prospectively assessed over a 3-month period. They provided information about
      their daily activities and their history of CLBP. Prognostic factors were
      analysed using univariate and multivariate logistic regression analyses. A
      physical examination was performed to record demographic (i.e. age, height and
      weight) and pain characteristics, and the intensity of pain was assessed using a
      numerical visual analogue scale. Disability was assessed using the Roland-Morris
      Disability Questionnaire (RMDQ). A simple measure generally used for sagittal
      plane screening purposes during growth was also utilized. RESULTS: Multivariate
      logistic regression analysis revealed that gender (OR = 1.70), RMDQ score (OR =
      0.51) and thoracic hyperkyphosis (C7 + L3 at the plumb-line distance) (OR = 1.57)
      were associated with CLBP. The final regression model explained 85.6% (R2 = 0.56;
      P < 0.001) of the variability. CONCLUSIONS: General practitioners can clinically
      and easily assess trunk posture in subjects with low back pain to identify
      subjects at higher risk of CLBP.

PMID- 30100310
TI  - Strength matters.

PMID- 30100311
TI  - Can we spread the risk? A demand-share perspective to sustained hamstring health.

PMID- 30100313
TI  - A 12-week supervised exercise therapy program for young adults with a meniscal
      tear: Program development and feasibility study.
AB  - OBJECTIVE: To describe the development and feasibility of an exercise therapy
      program for treatment of young adults (18-40 years of age) with a meniscal tear.
      METHODS: Researchers and experienced physical therapists developed a 12-week
      supervised neuromuscular and strengthening exercise therapy program based on
      clinical expertise and available evidence. Six patients (age range 22-39 years)
      considered eligible for meniscal surgery by an orthopedic surgeon underwent the
      program. Patients completed the Knee Injury and Osteoarthritis Outcome Score
      (KOOS) and evaluated the program during a semi-structured qualitative interview.
      Feedback from patients was included to finalize the exercise therapy program.
      RESULTS: Median improvements (Range) in KOOS subscales were 15 (0-33) for Pain,
      11 (-11 to 50) for Symptoms, 16 (3-37) for Function in daily living, 23 (10-45)
      for Function in sport and recreation, and 9 (-6 to 31) for Quality of life. The
      patients found the program relevant and effective with only a few short-lasting
      adverse events and important clinical improvements after four to ten weeks.
      Physical therapist supervision was considered important. No patients wanted
      surgery up to 6 month after the exercise therapy program. CONCLUSION: A
      neuromuscular and strengthening exercise therapy program was feasible and showed
      important improvement in a small group of young adults with meniscal tears.

PMID- 30100312
TI  - Can we spread the risk? A demand-share perspective to sustained hamstring health.
      Practical examples.
AB  - This short practical paper gives examples of exercises of synergists that assist
      the biceps femoris long head, the most commonly injured hamstring muscle in
      repeated sprint field sports (soccer, rugby) with the aim of reducing risk of or
      recurrence of injury. It is a companion to the theoretical piece of the same
      name.

PMID- 30100314
TI  - Effect of postural insoles on gait pattern in individuals with hemiparesis: A
      randomized controlled clinical trial.
AB  - INTRODUCTION: Recovering the ability to walk is an important goal of physical
      therapy for patients who have survived cerebrovascular accident (stroke).
      Orthotics can provide a reduction in plantar flexion of the ankle, leading to
      greater stability in the stance phase of the gait cycle. Postural insoles can be
      used to reorganize the tone of muscle chains, which exerts an influence on
      postural control through correction reflexes. The aim of the present study was to
      perform kinematic and spatiotemporal analyses of gait in stroke survivors with
      hemiparesis during postural insole usage. MATERIAL AND METHODS: Twenty stroke
      victims were randomly divided into two groups: 12 in the experimental group, who
      used insoles with corrective elements specifically designed for equinovarus foot,
      and eight in the control group, who used placebo insoles with no corrective
      elements. Both groups were also submitted to conventional physical therapy. The
      subjects were analyzed immediately following insole placement and after three
      months of insole usage. The SMART-D 140(r) system (BTS Engineering) with eight
      cameras sensitive to infrared light and the 32-channel SMART-D INTEGRATED
      WORKSTATION(r) were used for the three-dimensional gait evaluation. RESULTS:
      Significant improvements were found in kinematic range of movement in the ankle
      and knee as well as gains in ankle dorsiflexion and knee flexion in the
      experimental group in comparison to the control group after three months of using
      the insoles. CONCLUSION: Postural insoles offer significant benefits to stroke
      survivors regarding the kinematics of gait, as evidenced by gains in ankle
      dorsiflexion and knee flexion after three months of usage in combination with
      conventional physical therapy.

PMID- 30100315
TI  - Effects of Mat Pilates on hip and knee isokinetic torque parameters in elderly
      women.
AB  - This study aimed to analyze the effects of Mat Pilates on isokinetic torque of
      the lower limbs in elderly women. Fourteen elderly women (Age 62 +/- 3 yr)
      participated in 12 weeks of Mat Pilates training (60-min sessions, 3 times per
      week). Repetitions increased every 4 weeks and the difficulty of exercises
      progressed from beginner to intermediate and advanced. Peak torque was assessed
      before (week -4 and week 0, considered as a control period) and after 6 and 12
      weeks of a periodized Mat Pilates intervention. The results showed significant
      improvements (p < 0.05) in concentric and eccentric peak torque of knee flexors
      muscles, hip flexor and extensor muscles after 12 weeks. Mechanical work showed
      significant improvement (p < 0.05) for knee extensor muscles during eccentric
      contractions after week 12, for hip extensor muscles during concentric
      contractions week 12, and for flexor muscles during concentric and eccentric
      contractions after week 12. We conclude that the periodization of Mat Pilates
      induced significant improvements in multiple isokinetic torque parameters.

PMID- 30100316
TI  - The effects of cryotherapy versus cryostretching on clinical and functional
      outcomes in athletes with acute hamstring strain.
AB  - PURPOSE: Hamstring strain is a common sport injury that results in pain and
      functional limitation. Despite its high frequency in active populations, there is
      no agreement regarding the best method used for early intervention of hamstring
      strain. The aim of the present study was to compare the effects of cryotherapy
      and cryostretching on clinical and functional outcomes in athletes with acute
      hamstring strain. MATERIALS AND METHODS: Thirty seven elite athletes with an
      acute grade I or II hamstring strain were randomly assigned to either cryotherapy
      (n = 19) or cryostretching (n = 18) group, receiving 5 sessions of supervised
      treatment plus home-based intervention monitored by the therapist. Pre-treatment
      to post-treatment changes in pain, active and passive knee extension range of
      motion and functional status were compared between the two groups. RESULTS:
      Compared to cryotherapy, cryostretching resulted in larger improvement of
      function and passive knee extension range of motion. Changes in active knee
      extension range of motion and pain severity were not significantly different
      between the two groups. CONCLUSION: A rehabilitation protocol involving gentle
      stretching following cryotherapy is more effective than cryotherapy alone in the
      improvement of function and passive knee range of motion in patients with grade I
      and II hamstring strain.

PMID- 30100317
TI  - Lip closure training improves eating behaviors and prefrontal cortical
      hemodynamic activity and decreases daytime sleep in elderly persons.
AB  - Previous research suggests that aging-related deterioration of oral functions
      causes not only eating/swallowing disorders but also various conditions such as
      sleep disorders and higher-order brain dysfunction. The aim of the present study
      was to examine the effects of lip closure training on eating behavior, sleep, and
      brain function in elderly persons residing in an elder care facility. The 20
      elderly subjects (mean age, 86.3 +/- 1.0 years) were assigned to a control group
      or a lip closure training (LCT) group, in which an oral rehabilitation device was
      used for daily LCT sessions over a 4-week period. Before and after the 4-week
      intervention period, maximal lip closure force was measured, and prefrontal
      cortical hemodynamic activity (changes in oxygenated hemoglobin concentration)
      during lip closure movements was measured with (LCT group) or without (control
      group) use of the oral rehabilitation device. We also analyzed eating behavior
      and daytime sleep before and after the intervention period. Compared with the
      control group, the LCT group showed improved maximal lip closure force, shortened
      eating time, decreased food spill rates, and decreased daytime sleeping.
      Furthermore, compared with the control group, the LCT group showed a significant
      increase in prefrontal cortical activity during lip closure. In addition, the
      increase rate in the right dorsolateral prefrontal cortical activity after the
      intervention period was significantly correlated with the increase rate in the
      maximal lip closure force after the intervention period. These findings suggest
      that LCT is useful in elderly individuals with decreased eating/oral and
      cognitive functions without the risk of pulmonary aspiration during training.

PMID- 30100318
TI  - A randomised crossover trial comparing Thai and Swedish massage for fatigue and
      depleted energy.
AB  - BACKGROUND: The aim of this study was to compare the efficacy and social
      constructions of Thai massage (TM) and Swedish massage (SM) for patients
      experiencing fatigue or depleted energy. METHOD: Twenty participants were
      randomised to receive three once-weekly TM treatments and three once-weekly SM
      treatments, with crossover after three massages. Symptom checklists were
      administered at three time points and included Activation-Deactivation Adjective
      Check List and VAS Scale. Qualitative data were collected through semi-structured
      interviews and participants' diary entries. RESULTS: Both massage types enhanced
      physical, emotional and mental wellbeing through improved sleep, relaxation,
      relief of stress and relief of muscular tension. TM alone showed specific
      energising and psychological stimulation results, along with carry-over effect
      and longer lasting benefits. Ninety-five percent of participants found relief
      from their initial reason presenting symptoms. CONCLUSION: TM or SM can relieve
      symptoms of fatigue or low energy by releasing stress, promoting relaxation,
      relieving muscular aches and pains and improving energy. SM results in a larger
      effect in relaxation and improved sleep whereas TM results in a larger effect in
      energising, rejuvenating and mentally stimulating effects.

PMID- 30100319
TI  - The effect of kinesiotaping on hand function in stroke patients: A pilot study.
AB  - Upper extremity motor impairment is one of the most prevalent problems following
      stroke. Considering the functional importance of the upper extremity in the daily
      life, the purpose of this study was to investigate the effect of kinesiotaping
      (KT) on hand function and spasticity in individuals following a stroke. Eight
      individuals who had experienced a stroke, with their age ranging from 47 to 66,
      participated in this pretest-posttest clinical study. An I- strip of tape was
      placed on the extensor muscles of the forearm. Primary outcome measures were the
      Modified Modified Ashwoth Scale, Box and Block test, and Nine Hole Peg test. At
      the immediate assessment, there were significant differences between two hand
      function tests scores. Secondary assessment was done after one week and the
      results showed significant differences between two hand function test scores.
      There was no significant change in flexor muscles spasticity after the
      intervention. This pilot study indicated that KT in the direction of the extensor
      muscles could result in better hand function in stroke patients.

PMID- 30100320
TI  - Effect of remote myofascial release on hamstring flexibility in asymptomatic
      individuals - A randomized clinical trial.
AB  - BACKGROUND: The existence of continuity between fascia and muscles that may be
      anatomically distant from each other is emphasized in the tensegrity principle.
      Despite evidence from in vitro studies, there is a dearth of literature
      concerning the in vivo behavior of these connections. AIM: To compare the effect
      of Static Stretching (SS) of hamstrings with remote Myofascial Release (MFR)
      (bilateral plantar fascia and suboccipital region) and a combination of SS and
      remote MFR on hamstring flexibility. The secondary aim of this study was to
      investigate the difference between therapist administered and self-administered
      interventions. DESIGN: Three arm assessor-blinded Randomized Clinical Trial
      (RCT). PARTICIPANTS: Fifty-eight asymptomatic participants (16 Males; Mean age
      22.69 +/- 2.65 years). METHOD: Participants with tight hamstrings defined by a
      passive Knee Extension Angle (KEA) > 20 degrees  were included in the study and
      were assigned to one of the three groups. Group A (n = 19) was SS, group B (n =
      20) was remote MFR, group C (n = 19) was a combination group who received both SS
      and remote MFR. Seven sessions of therapist administered intervention were
      delivered over a period of 10 days, which was followed by a 2-week self
      administered home program. KEA and Sit and Reach Test (SRT) were used as outcomes
      and measurements were performed at baseline, end of the seventh session and after
      atwo-week follow-up. RESULTS: The results demonstrated that hamstring flexibility
      improved in all three groups after therapist administered interventions (p <
      0.05), whereas, group C demonstrated additional benefits. None of the groups
      showed a statistically significant (p > 0.05) change in the KEA with self
      intervention. CONCLUSION: The findings of this study indicated that all three
      interventions were effective in improving hamstring flexibility in young
      asymptomatic individuals when performed by the therapist.

PMID- 30100321
TI  - International Surgery Electives During General Surgery Residency: A 9-Year
      Experience at an Independent Academic Center.
AB  - OBJECTIVE: International experiences are an increasingly emphasized feature of
      general surgery residency programs. In 2008, an international elective (IE) was
      implemented for general surgery residents at our institution. This effort was
      augmented by the establishment of a pathway for formal approval of IEs by the
      American Board of Surgery and Accreditation Council for Graduate Medical
      Education in 2012. DESIGN: A retrospective review of Accreditation Council for
      Graduate Medical Education case logs was completed. IE operative volumes were
      compared to home institution general surgery service volumes. An electronic
      survey of IE participants was conducted to assess preresidency goals, prior
      international exposure, overall experience on IEs, and current or planned
      engagement with international experiences, volunteerism, or global philanthropy.
      SETTING: Independent Academic Medical Center. PARTICIPANTS: Fourteen general
      surgery residents who participated in IEs from 2008 to 2017. RESULTS: IE
      locations included the Dominican Republic (9), Ecuador (1), Ethiopia (3), and
      Nicaragua (1). IEs were a first-time international surgical experience for 10
      (71%) residents. Nine (64%) reported that they would not or may not have
      participated in an IE during residency had established opportunities not been
      available. Ten residents had graduated at the time of this study and 3 of them
      have participated in international service. Median case volumes were 17 cases per
      week during IEs compared to 8 cases per week for residents on home institution
      rotations. Residents were exposed to a variety of first-time operations during
      IEs including open cholecystectomies, gynecologic procedures, thyroidectomies for
      goiter, and prostatectomies. CONCLUSIONS: Incorporation of IEs into our general
      surgery residency has demonstrated numerous benefits. IE participation provides
      valuable operative experience in both volume and variety, and can be especially
      impactful for those who may not have elected to pursue such opportunities
      independently. These experiences have the potential to empower general surgery
      residents to invest in similar practices and acts of generosity in their future
      careers.

PMID- 30100322
TI  - Correlation Between Cost of Publication and Journal Impact. Comprehensive Cross
      sectional Study of Exclusively Open-Access Surgical Journals.
AB  - OBJECTIVES: As open-access journals have become increasingly common, it has
      provided more options for researchers to publish their work and improved access
      of information to the public. However, some open-access journals charge the
      authors processing fee on submission. In certain cases, this can be rather
      expensive. This study is the first study to specifically assess the cost of
      publishing in exclusively open-access, peer-reviewed surgical journals, and their
      correlation with journal impact, in the form of 6 bibliometrics. DESIGN AND
      SETTING: This is a cross-sectional study. A list of journals is compiled using
      the SCImago Journal & Country Rank and Directory of Open Access Journals. 6
      indices are measured - impact factor, SCOPUS h-index, SCImago journal rank
      indicator (SJR), Eigenfactor, Article Influence Score and Google h5 index. The
      cost of publication (in USD$) of a research article (maximum of 6 pages) is used
      as a baseline. RESULTS: 89 research journals are included. The median cost of
      publication is USD$100 (range [0-2580]). 47% are free of charge. 13% can cost
      more than USD$2000 per article. SJR and Google h5 index appear to be the only
      indices that correlate linearly with the cost (p = 0.015 and 0.041,
      respectively), although the correlations are weak. 3 indices, namely impact
      factor, SJR and Article Influence Score appear to have very strong correlations
      with each other (Pearson coefficient > 0.90). CONCLUSIONS: From this study, the
      cost of publishing in open-access journals bears little correlation to their
      impact; this poses a dilemma for researchers without significant funding.
      Therefore, authors and funders must consider cautiously when submitting to these
      journals.

PMID- 30100323
TI  - Financial Value Analysis of Surgical Residency Programs: An Argument Against
      Replacement.
AB  - OBJECTIVE: To quantify the replacement cost of patient care provided by surgical
      residents and build a Graduate Medical Education (GME) value analysis model.
      DESIGN: Our Graduate Medical Education Executive Steering Committee designed a
      resident replacement cost model, based on patient care hours (adjusted for
      educational activities and a clinical efficiency factor, differential cost of
      faculty supervision for residents vs. APPs, and current program financials
      (revenue minus expenses). Strategic value planning included: academic
      productivity (local and national conference presentations, book chapters and
      publications and Senior Staff recruitment and retention. SETTING: Department of
      Surgery at Baylor Scott & White Medical Center, a tertiary institution located in
      Temple, TX. PARTICIPANTS: Our replacement model was applied to a sample 30
      position residency program. RESULTS: Modeling a 30-position residency program,
      replacement cost approaches 4.5 million dollars, based on a 1:3 Senior Staff-to
      APP replacement ratio. A complete APP replacement complement has a projected cost
      of 3.1 million dollars, while replacement with Senior Staff approaches 9 million
      dollars. CONCLUSIONS: We present a novel model for residency value analysis
      allowing for reproducible and standardized results across multiple residency
      programs. Challenges inherent to GME, such as clinical efficiency and the cost of
      faculty supervision, are accounted for. Quantifying resident replacement cost and
      financial value is a powerful tool when discussing institutional workforce
      planning within the current financial climate of healthcare.

PMID- 30100325
TI  - Prediction of Postoperative Surgical Risk: A Needs Assessment for a Medical
      Student Curriculum.
AB  - OBJECTIVE: Medical students' abilities to predict postoperative complications and
      death are unknown. We hypothesize that medical students will lack confidence in
      determining surgical risk and will significantly overestimate surgical risk for
      post-operative morbidities and mortality. DESIGN: Participants were invited to
      participate in an electronic, anonymous survey to assess their ability to predict
      surgical risk. The survey presented 7 complex clinical scenarios representative
      of a diverse general surgery practice. Participants were asked to assess the
      likelihood of different morbidities and mortality on a 0-100% scale, and
      predictions were compared to the ACS NSQIP risk calculator. SETTING: Yale School
      of Medicine, New Haven, Connecticut; Tertiary medical center PARTICIPANTS: Third
      year medical students on their surgery clerkship as well as general surgery
      residents were invited to participate. RESULTS: Most students were not confident
      about predicting postoperative complications (83.3%) or mortality (70.8%). Most
      students did not feel that the surgery clerkship adequately prepared them to
      assess surgical risk (69.6%). When compared to surgical residents for most
      presented cases (57% of cases), students and residents similarly overestimated
      postoperative morbidities and mortality. Estimates varied significantly, with
      wide 95% confidence intervals. Only 17% of NSQIP predicted estimates fell within
      the 95% confidence intervals. CONCLUSIONS: Medical students overestimate
      morbidity and mortality following surgery in complex patients. Additionally, they
      lack confidence in their ability to predict surgical complications. A formal
      curriculum for risk prediction is needed for medical students.

PMID- 30100324
TI  - Training for a Career in Rural and Nonmetropolitan Surgery-A Practical Needs
      Assessment.
AB  - OBJECTIVE: The current shortage of surgeons in rural and smaller communities is
      predicted to get worse. In this study, we solicited practicing rural surgeons'
      opinions about the skill set needed in a rural practice in order to inform
      curriculum development for general surgery residents who intend to embark on
      rural careers. DESIGN: We developed an online survey consisting of demographic
      questions and closed- and open-ended questions regarding current practice
      environment and scope of practice. Priorities for training were identified using
      descriptive analyses of both the quantitative and qualitative data, including
      frequency of responses regarding specific skills training. PARTICIPANTS: We
      surveyed currently practicing surgeons who subscribe to the American College of
      Surgeons Rural Surgery listserv. RESULTS: 237 surgeons from 49 states and 1
      Canadian territory responded; 60% of participants had been in practice for 20 or
      more years, and 70% did not pursue subspecialty training. Valuable skills
      identified for rural surgeons were: endoscopy, advanced laparoscopy, and basic
      non-general surgery subspecialty procedures. Regardless of years of practice or
      setting, respondents felt that rural experience during residency was highly
      valuable (82%) and overwhelmingly supported training future rural surgeons at
      residency programs with broad general surgery experiences and high case volumes
      with no or few fellows. CONCLUSIONS: Practicing rural surgeons identify
      endoscopy, basic non-general surgery subspecialty procedures, and advanced
      laparoscopy as key components of their current practice. These skills may not be
      strongly emphasized in traditional general surgery training programs. Surgical
      educators should focus on developing curricula that emphasize these areas in
      order to prepare residents for careers in rural surgery.

PMID- 30100326
TI  - Individual variability in humoral response of immunized outbred mice and cross
      reactivity with prevalent Brazilian Neisseria meningitidis strains.

PMID- 30100327
TI  - Hydrogen gas inhalation during ex vivo lung perfusion of donor lungs recovered
      after cardiac death.
AB  - BACKGROUND: Ex vivo lung perfusion (EVLP) is a system that circulates
      normothermic perfusate into procured lungs, allowing for improved lung function
      and lung assessment. We investigated whether ventilation with hydrogen gas during
      EVLP improves the donation after cardiac death lung function and whether this
      effect persists after actual transplantation. METHODS: Ten pigs were randomly
      divided into a control group (n = 5) and a hydrogen group (n = 5). No treatment
      was administered to induce warm ischemic injury for 1 hour after cardiac arrest,
      and EVLP was applied in procured lungs for 4 hours. During EVLP, the control
      group was given room air for respiration, and the hydrogen group was given 2%
      hydrogen gas. After EVLP, the left lung graft was orthotopically transplanted
      into the recipient and reperfused for 3 hours. During EVLP and reperfusion, the
      functional parameters and arterial blood gas analysis (ABGA) were measured every
      hour. Superoxide dismutase, heme oxygenase, interleukin (IL)-6, IL-10, tumor
      necrosis factor-alpha, and nucleotide-binding oligomerization domain-like
      receptor protein 3 were evaluated in lung tissue after reperfusion. Pathologic
      evaluations were performed, and the degree of apoptosis was evaluated. The
      wet/dry ratio was measured. RESULTS: During EVLP and reperfusion, functional
      parameters and ABGA results were better in the hydrogen group. The expressions of
      superoxide dismutase (p = 0.022) and heme oxygenase-1 (p = 0.047) were
      significantly higher in the hydrogen group. The expressions of IL-6 (p = 0.024)
      and nucleotide-binding oligomerization domain-like receptor protein 3 (p = 0.042)
      were higher in the control group, but IL-10 (p = 0.037) was higher in the
      hydrogen group. The lung injury severity score and the number of apoptotic cells
      were higher and the degree of pulmonary edema was more severe in the control
      group than in the hydrogen group. CONCLUSIONS: Hydrogen gas inhalation during
      EVLP improved donation after cardiac death lung function via reduction of
      inflammation and apoptosis, and this effect persisted after LTx.

PMID- 30100328
TI  - Identification of small molecule inhibitors for differentially expressed miRNAs
      in gastric cancer.
AB  - Gastric cancer is a common cancer in the world with higher incidence rates. Micro
      RNAs (miRNAs) are known to control biological processes and are also involved in
      the initiation and progression of numerous cancers. The aim of this study was to
      identify small molecule inhibitors using bioinformatics methods for over
      expressed miRNAs that are known to play a major role in the genesis of gastric
      cancer. Our study included three datasets from Gene expression omnibus (GEO)
      database and we used bioinformatics tool to identify differentially expressed
      miRNAs in all the three datasets. Gene ontology and pathway enrichment analysis
      of the experimentally validated miRNA target genes and their linkage to
      oncogenesis were analyzed. Target genes thus identified were found to be linked
      with the major pathways of cancer. We were interested in identifying small
      molecules which are specific to over-expressed miRNAs which can arrest
      oncogenesis. Thus, the computer aided high throughput virtual screening was
      carried out to identify potent small molecules for over expressed miRNAs in
      gastric cancer using Glide. Based on docking score top five ligands specific for
      each miRNAs were identified.

PMID- 30100329
TI  - TEMPI Syndrome: Erythrocytosis in Plasma Cell Dyscrasia.
AB  - TEMPI (telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal
      gammopathy, perinephric fluid collections, intrapulmonary shunting) syndrome is a
      newly described clinical entity that is generally considered a plasma cell
      dyscrasia with multiple system involvement. The etiology and pathophysiology of
      this condition remains elusive. Nevertheless, clonal plasma cells and monoclonal
      protein appear to be major contributors. The early diagnosis of TEMPI syndrome is
      essential because therapies targeting the underlying plasma cells can lead to a
      dramatic response. Bortezomib-based chemotherapy, daratumumab monotherapy, and
      autologous hematopoietic stem cell transplantation can result in reversal of most
      manifestations. Nevertheless, the diagnosis of TEMPI syndrome remains a
      substantial challenge owing to its rarity and the complexity of clinical
      presentations. TEMPI syndrome is often misdiagnosed as other causes of
      erythrocytosis, resulting in a delayed diagnosis and further clinical
      deterioration. The aim of the present review was to present the clinical and
      biologic features of TEMPI syndrome, highlighting the differential diagnosis and
      outlining the present understanding of its pathophysiology and treatment.

PMID- 30100331
TI  - Novel method of infant chest compression. Does the arrangement of the thumbs
      matter?

PMID- 30100330
TI  - Outcomes of Intermediate Risk Karyotype Acute Myeloid Leukemia in First Remission
      Undergoing Autologous Stem Cell Transplantation Compared With Allogeneic Stem
      Cell Transplantation and Chemotherapy Consolidation: A Retrospective, Propensity
      score Adjusted Analysis.
AB  - INTRODUCTION: Optimal post-remission therapy (PRT) for intermediate risk acute
      myeloid leukemia remains an area of ongoing research. We aimed to retrospectively
      compare outcomes following autologous stem cell transplantation (autoSCT) with
      allogeneic SCT (alloSCT) and consolidation chemotherapy (CMT) in patients with
      intermediate-risk karyotype AML in first complete remission. PATIENTS AND
      METHODS: We compared overall survival (OS) and leukemia-free survival (LFS) using
      propensity score (PS)-adjusted analysis of patients receiving PRT with autoSCT,
      matched sibling (MSD) alloSCT, unrelated/mismatch (UD/MM) alloSCT, and CMT. We
      included patients diagnosed between 1984 and 2003 (period of autoSCT at our
      center) in CR1 following induction CMT and received at least 2 consolidative
      cycles. RESULTS: We identified 190 patients (62 MSD-alloSCT, 18 UD/MM-alloSCT, 30
      autoSCT, and 80 CMT). Baseline characteristics were used for PS calculation and
      were well-balanced after weight adjustment. The median follow-up for patients
      surviving beyond 1 year was 8.7 years. We excluded 55 patients based on PS
      calculation. Adjusted multivariate hazard ratio (HR), 95% confidence interval
      (CI) and P-value for OS, considering CMT as reference, were: MSD-alloSCT (HR,
      0.4; 95% CI, 0.2-0.8; P = .009), UD/MM-alloSCT (HR, 1.5; 95% CI, 0.6-3.9; P =
      .363), and autoSCT (HR, 1.2; 95% CI, 0.5-3.1; P = .666), respectively. Adjusted
      multivariate HR, 95% CI and P-value for LFS were MSD-alloSCT (HR, 0.3; 95% CI,
      0.2-0.6; P < .001), UD/MM-alloSCT (HR, 1.1; 95% CI, 0.4-2.7; P = .854), and
      autoSCT (HR, 0.8; 95% CI, 0.3-2.2; P = .697), respectively. CONCLUSION: Patients
      with intermediate risk-karyotype acute myeloid leukemia who underwent MSD-alloSCT
      in first complete remission had the best outcomes. There were no survival
      differences between autoSCT, UD/MM-alloSCT, and CMT. Further study incorporating
      molecular changes and minimal residual disease status is warranted to select
      appropriate patients for autoSCT.

PMID- 30100332
TI  - Hospital Information Technology is critical to the success of a point-of-care
      ultrasound program.

PMID- 30100333
TI  - On-demand synchronous audio video telemedicine visits are cost effective.
AB  - INTRODUCTION: Claims data raises the possibility that on demand telemedicine
      programs might increase new utilization, offsetting the cost benefits described
      in some retrospective analyses. We prospectively evaluated the cost of a
      synchronous audio-video on-demand telemedicine taking into account both what
      patients would have done instead of the telemedicine visit as well as the care
      patients received after the visit. MATERIALS AND METHODS: We conducted a
      prospective observational study of patients who received care from an on-demand
      telemedicine program. At the time of the visit, we surveyed patients about the
      alternative care that would have been requested, if they had not done the
      telemedicine visit. We also obtained information following the visit about what
      further care was received. Using cost data derived from the literature we
      performed a sensitivity analysis to determine the cost impact of the on-demand
      telemedicine visit. RESULTS: There were 650 patients enrolled with a mean age of
      37 who were 68% female; 74% had their care concerns resolved on the telemedicine
      visit; only 16% would have "done nothing" if they had not done the telemedicine
      visit, representing possible new utilization. Net cost savings per telemedicine
      visit was calculated to range from $19-$121 per visit. CONCLUSIONS: In our on
      demand telemedicine program, we found the majority of health concerns could be
      resolved in a single consultation and new utilization was infrequent. Synchronous
      audio-video telemedicine consults resulted in short-term cost savings by
      diverting patients from more expensive care settings.

PMID- 30100334
TI  - Tracheal rupture as a result of coughing.
AB  - Tracheal rupture is mostly traumatic or iatrogenic. A few cases of spontaneous
      tracheal rupture have been reported in literature and all of them have been
      described posterior membraneous wall which is the weakest portion of trachea. In
      most of such cases, predisposing factors that weaken the tracheal structure were
      present. We presented the first case of spontaneous anterolateral tracheal
      rupture as a result of coughing that caused no respiratory distress and that
      spontaneously recovered without any complications. A 24 year old male presented
      to the emergency department with sore throat. After eating chicken shawarma, the
      patient felt a lump in his throat and coughed. After coughing, a tearing like and
      severe pain developed at his neck's front region radiating to his shoulders and
      back. On past medical history, the patient had no known diseases and had no
      history of use of medications. Physical examination findings were unremarkable
      except for neck tenderness. Pneumomediastinum, free air within the cervical
      fascias and a 4mm tracheal mural defect on the left anterolateral side at the
      level superior to the manubrium was observed in computerised tomography scan of
      neck and chest. The patient had no shortness of breath and therefore urgent
      surgery was not considered. Increase in free air was not seen in the control x
      rays 6 hours later. The patient with a foriegn nationality left the emergency at
      his own will. He was contacted one month later via telephone. The patient said
      that his neck pain subsided and had no other complaints.

PMID- 30100335
TI  - Utilization of chest CT for injured patients during visits to U.S. emergency
      departments: 2012-2015.
AB  - INTRODUCTION: Increased use of computed tomography (CT) during injury-related
      Emergency Department (ED) visits has been reported, despite increased awareness
      of CT radiation exposure risks. We investigated national trends in the use of
      chest CT during injury-related ED visits between 2012 and 2015. METHODS:
      Analyzing injury-related ED visits from the 2012-2015 United States (U.S.)
      National Hospital Ambulatory Medical Care Survey (NHAMCS), we determined the
      percentage of visits that had a chest CT and the diagnostic yield of these chest
      CTs for clinically-significant findings. We used survey-weighted multivariable
      logistic regression to determine which patient and visit characteristics were
      associated with chest CT use. RESULTS: Injury-related visits accounted for 30% of
      the 135 million yearly ED visits represented in NHAMCS. Of these visits, 817,480
      (2%) received a chest CT over the study period. The diagnostic yield was 3.88%.
      Chest CT utilization did not change significantly from a rate of 1.73% in 2012 to
      a rate of 2.31% in 2015 (p = 0.14). Multivariate logistic regression demonstrated
      increased odds of chest CT for patients seen by residents versus by attendings
      (adjusted odds ratio [AOR] 2.08, 95% confidence interval [CI] 1.41-3.08).
      Patients aged 18-59 and 60+ had higher AORs (5.75, CI 3.44-9.61 and 9.81, CI 5.90
      16.33, respectively) than those <18 years of receiving chest CT. CONCLUSIONS:
      Overall chest CT utilization showed an increased trend from 2012 to 2015, but the
      results were not statistically significant.

PMID- 30100336
TI  - Intravenous paracetamol versus dexketoprofen in acute musculoskeletal trauma in
      the emergency department: A randomised clinical trial.
AB  - INTRODUCTION: Musculoskeletal system traumas are among the most common
      presentations in the emergency departments. In the treatment of traumatic
      musculoskeletal pain, paracetamol and non-steroidal anti-inflammatory analgesics
      (NSAID) are frequently used. Our aim in this study is to compare the efficacy of
      intravenous dexketoprofen and paracetamol in the treatment of traumatic
      musculoskeletal pain. METHODS: This prospective, randomised, double blind,
      controlled study was conducted in a tertiary care emergency unit. The
      participating patients were randomised into two groups to receive either 50 mg of
      dexketoprofen or 1000 mg of paracetamol intravenously by rapid infusion in 150 mL
      of normal saline. Visual analogue scale (VAS), Numeric Rating Scala (NRS) and
      Verbal Rating Scale (VRS) was employed for pain measurement at baseline, after
      15, after 30 and after 60 mins. RESULTS: 200 patients were included in the final
      analysis. The median age of the paracetamol group was 34 (24-48), while that of
      the dexketoprofen group was 35 (23-50), and 63% (n = 126) of them consisted of
      men. Paracetamol and dexketoprofen administration reduced VAS pain scores over
      time (p = 0.0001). Median reduction in VAS score at 60 min was 55 (IQR 30-65) for
      the paracetamol group and 50(IQR 30.25-60) for the dexketoprofen group. There was
      no statistically significant difference between the paracetamol and dexketoprofen
      groups in terms of VAS reductions (p = 0.613). CONCLUSION: Intravenous
      paracetamol and dexketoprofen seem to produce equivalent pain relief for acute
      musculoskeletal trauma in the emergency department. CLINICALTRIALS. GOV NO:
      NCT03428503.

PMID- 30100337
TI  - Ectopic BASL Reveals Tissue Cell Polarity throughout Leaf Development in
      Arabidopsis thaliana.
AB  - Tissue-wide polarity fields, in which cell polarity is coordinated across the
      tissue, have been described for planar organs such as the Drosophila wing and are
      considered important for coordinating growth and differentiation [1]. In planar
      plant organs, such as leaves, polarity fields have been identified for subgroups
      of cells, such as stomatal lineages [2], trichomes [3, 4], serrations [5], or
      early developmental stages [6]. Here, we show that ectopic induction of the
      stomatal protein BASL (BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE) reveals a
      tissue-wide epidermal polarity field in leaves throughout development. Ectopic
      GFP-BASL is typically localized toward the proximal end of cells and to one lobe
      of mature pavement cells, revealing a polarity field that aligns with the
      proximodistal axis of the leaf (base to tip). The polarity field is largely
      parallel to the midline of the leaf but diverges in more lateral positions,
      particularly at later stages in development, suggesting it may be deformed during
      growth. The polarity field is observed in the speechless mutant, showing that it
      is independent of stomatal lineages, and is observed in isotropic cells, showing
      that cell shape anisotropy is not required for orienting polarity. Ectopic BASL
      forms convergence and divergence points at serrations, mirroring epidermal PIN
      polarity patterns, suggesting a common underlying polarity mechanism. Thus, we
      show that similar to the situation in animals, planar plant organs have a tissue
      wide cell polarity field, and this may provide a general cellular mechanism for
      guiding growth and differentiation.

PMID- 30100338
TI  - Basal Forebrain and Brainstem Cholinergic Neurons Differentially Impact Amygdala
      Circuits and Learning-Related Behavior.
AB  - The central cholinergic system and the amygdala are important for motivation and
      mnemonic processes. Different cholinergic populations innervate the amygdala, but
      it is unclear how these projections impact amygdala processes. Using optogenetic
      circuit-mapping strategies in choline acetyltransferase (ChAT)-cre mice, we
      demonstrate that amygdala-projecting basal forebrain and brainstem ChAT
      containing neurons can differentially affect amygdala circuits and behavior.
      Photo-activating ChAT terminals in vitro revealed the underlying synaptic impact
      of brainstem inputs to the central lateral division to be excitatory, mediated
      via the synergistic glutamatergic activation of AMPA and NMDA receptors. In
      contrast, stimulating basal forebrain inputs to the basal nucleus resulted in
      endogenous acetylcholine (ACh) release, resulting in biphasic inhibition
      excitation responses onto principal neurons. Such response profiles are
      physiological hallmarks of neural oscillations and could thus form the basis of
      ACh-mediated rhythmicity in amygdala networks. Consistent with this, in vivo
      basal forebrain ChAT+ activation strengthened amygdala basal nucleus theta and
      gamma frequency rhythmicity, both of which continued for seconds after
      stimulation and were dependent on local muscarinic and nicotinic receptor
      activation, respectively. Activation of brainstem ChAT-containing neurons,
      however, resulted in a transient increase in central lateral amygdala activity
      that was independent of cholinergic receptors. In addition, driving these
      respective inputs in behaving animals induced opposing appetitive and defensive
      learning-related behavioral changes. Because learning and memory are supported by
      both cellular and network-level processes in central cholinergic and amygdala
      networks, these results provide a route by which distinct cholinergic inputs can
      convey salient information to the amygdala and promote associative biophysical
      changes that underlie emotional memories.

PMID- 30100340
TI  - Global Determinants of Navigation Ability.
AB  - Human spatial ability is modulated by a number of factors, including age [1-3]
      and gender [4, 5]. Although a few studies showed that culture influences
      cognitive strategies [6-13], the interaction between these factors has never been
      globally assessed as this requires testing millions of people of all ages across
      many different countries in the world. Since countries vary in their geographical
      and cultural properties, we predicted that these variations give rise to an
      organized spatial distribution of cognition at a planetary-wide scale. To test
      this hypothesis, we developed a mobile-app-based cognitive task, measuring non
      verbal spatial navigation ability in more than 2.5 million people and sampling
      populations in every nation state. We focused on spatial navigation due to its
      universal requirement across cultures. Using a clustering approach, we find that
      navigation ability is clustered into five distinct, yet geographically related,
      groups of countries. Specifically, the economic wealth of a nation was predictive
      of the average navigation ability of its inhabitants, and gender inequality was
      predictive of the size of performance difference between males and females. Thus,
      cognitive abilities, at least for spatial navigation, are clustered according to
      economic wealth and gender inequalities globally, which has significant
      implications for cross-cultural studies and multi-center clinical trials using
      cognitive testing.

PMID- 30100341
TI  - Systematic Revision of Symbiodiniaceae Highlights the Antiquity and Diversity of
      Coral Endosymbionts.
AB  - The advent of molecular data has transformed the science of organizing and
      studying life on Earth. Genetics-based evidence provides fundamental insights
      into the diversity, ecology, and origins of many biological systems, including
      the mutualisms between metazoan hosts and their micro-algal partners. A well
      known example is the dinoflagellate endosymbionts ("zooxanthellae") that power
      the growth of stony corals and coral reef ecosystems. Once assumed to encompass a
      single panmictic species, genetic evidence has revealed a divergent and rich
      diversity within the zooxanthella genus Symbiodinium. Despite decades of
      reporting on the significance of this diversity, the formal systematics of these
      eukaryotic microbes have not kept pace, and a major revision is long overdue.
      With the consideration of molecular, morphological, physiological, and ecological
      data, we propose that evolutionarily divergent Symbiodinium "clades" are
      equivalent to genera in the family Symbiodiniaceae, and we provide formal
      descriptions for seven of them. Additionally, we recalibrate the molecular clock
      for the group and amend the date for the earliest diversification of this family
      to the middle of the Mesozoic Era (~160 mya). This timing corresponds with the
      adaptive radiation of analogs to modern shallow-water stony corals during the
      Jurassic Period and connects the rise of these symbiotic dinoflagellates with the
      emergence and evolutionary success of reef-building corals. This improved
      framework acknowledges the Symbiodiniaceae's long evolutionary history while
      filling a pronounced taxonomic gap. Its adoption will facilitate scientific
      dialog and future research on the physiology, ecology, and evolution of these
      important micro-algae.

PMID- 30100339
TI  - C. elegans Eats Its Own Intestine to Make Yolk Leading to Multiple Senescent
      Pathologies.
AB  - Aging (senescence) is characterized by the development of numerous pathologies,
      some of which limit lifespan. Key to understanding aging is discovery of the
      mechanisms (etiologies) that cause senescent pathology. In C. elegans, a major
      senescent pathology of unknown etiology is atrophy of its principal metabolic
      organ, the intestine. Here we identify a cause of not only this pathology but
      also of yolky lipid accumulation and redistribution (a form of senescent
      obesity): autophagy-mediated conversion of intestinal biomass into yolk.
      Inhibiting intestinal autophagy or vitellogenesis rescues both visceral
      pathologies and can also extend lifespan. This defines a disease syndrome leading
      to multimorbidity and contributing to late-life mortality. Activation of gut-to
      yolk biomass conversion by insulin/IGF-1 signaling (IIS) promotes reproduction
      and senescence. This illustrates how major, IIS-promoted senescent pathologies in
      C. elegans can originate not from damage accumulation but from direct effects of
      futile, continued action of a wild-type biological program (vitellogenesis).

PMID- 30100343
TI  - Actin-Network Architecture Regulates Microtubule Dynamics.
AB  - Coordination between actin filaments and microtubules is critical to complete
      important steps during cell division. For instance, cytoplasmic actin filament
      dynamics play an active role in the off-center positioning of the spindle during
      metaphase I in mouse oocytes [1-3] or in gathering the chromosomes to ensure
      proper spindle formation in starfish oocytes [4, 5], whereas cortical actin
      filaments control spindle rotation and positioning in adherent cells or in mouse
      oocytes [6-9]. Several molecular effectors have been found to facilitate
      anchoring between the meiotic spindle and the cortical actin [10-14]. In vitro
      reconstitutions have provided detailed insights in the biochemical and physical
      interactions between microtubules and actin filaments [15-20]. Yet how actin
      meshwork architecture affects microtubule dynamics is still unclear. Here, we
      reconstituted microtubule aster in the presence of a meshwork of actin filaments
      using confined actin-intact Xenopus egg extracts. We found that actin filament
      branching reduces the lengths and growth rates of microtubules and constrains the
      mobility of microtubule asters. By reconstituting the interaction between dynamic
      actin filaments and microtubules in a minimal system based on purified proteins,
      we found that the branching of actin filaments is sufficient to block microtubule
      growth and trigger microtubule disassembly. In a further exploration of Xenopus
      egg extracts, we found that dense and static branched actin meshwork perturbs
      monopolar spindle assembly by constraining the motion of the spindle pole.
      Interestingly, monopolar spindle assembly was not constrained in conditions
      supporting dynamic meshwork rearrangements. We propose that branched actin
      filament meshwork provides physical barriers that limit microtubule growth.

PMID- 30100342
TI  - Phase-Locked Stimulation during Cortical Beta Oscillations Produces Bidirectional
      Synaptic Plasticity in Awake Monkeys.
AB  - The functional role of cortical beta oscillations, if any, remains unresolved.
      During oscillations, the periodic fluctuation in excitability of entrained cells
      modulates transmission of neural impulses and periodically enhances synaptic
      interactions. The extent to which oscillatory episodes affect activity-dependent
      synaptic plasticity remains to be determined. In nonhuman primates, we delivered
      single-pulse electrical cortical stimulation to a "stimulated" site in
      sensorimotor cortex triggered on a specific phase of ongoing beta (12-25 Hz)
      field potential oscillations recorded at a separate "triggering" site.
      Corticocortical connectivity from the stimulated to the triggering site as well
      as to other (non-triggering) sites was assessed by cortically evoked potentials
      elicited by test stimuli to the stimulated site, delivered outside of oscillatory
      episodes. In separate experiments, connectivity was assessed by intracellular
      recordings of evoked excitatory postsynaptic potentials. The conditioning
      paradigm produced transient (1-2 s long) changes in connectivity between the
      stimulated and the triggering site that outlasted the duration of the oscillatory
      episodes. The direction of the plasticity effect depended on the phase from which
      stimulation was triggered: potentiation in depolarizing phases, depression in
      hyperpolarizing phases. Plasticity effects were also seen at non-triggering sites
      that exhibited oscillations synchronized with those at the triggering site. These
      findings indicate that cortical beta oscillations provide a spatial and temporal
      substrate for short-term, activity-dependent synaptic plasticity in primate
      neocortex and may help explain the role of oscillations in attention, learning,
      and cortical reorganization.

PMID- 30100344
TI  - Temporal Regulation of ESCO2 Degradation by the MCM Complex, the CUL4-DDB1-VPRBP
      Complex, and the Anaphase-Promoting Complex.
AB  - Sister chromatid cohesion, mediated by cohesin, is required for accurate
      chromosome segregation [1, 2]. This process requires acetylation of cohesin
      subunit SMC3 by evolutionarily conserved cohesin acetyltransferases: Eco1 in
      budding yeast; XEco1 and XEco2 in Xenopus; and ESCO1 and ESCO2 in human [3-10].
      Eco1 is recruited to chromatin through physical interaction with PCNA [11] and is
      degraded by the Skp1/Cul1/F-box protein complex after DNA replication to prevent
      ectopic cohesion formation [12]. In contrast, XEco2 recruitment to chromatin
      requires prereplication complex formation [13] and is degraded by the anaphase
      promoting complex (APC) [14]. In human, whereas ESCO1 is expressed throughout the
      cell cycle, ESCO2 is detectable in S phase and is degraded after DNA replication
      [6, 15]. Although PDS5, a cohesin regulator, preferentially promotes ESCO1
      dependent SMC3 acetylation [16], little is known about the molecular basis of the
      temporal regulation of ESCO2. Here, we show that ESCO2 is recruited to chromatin
      before PCNA accumulation. Whereas no interaction between PCNA and ESCO proteins
      is observed, ESCO2, but not ESCO1, interacts with the MCM complex through a
      unique ESCO2 domain. Interestingly, the interaction is required to protect ESCO2
      from proteasomal degradation and is attenuated in late S phase. We also found
      that ESCO2 physically interacts with the CUL4-DDB1-VPRBP E3 ubiquitin ligase
      complex in late S phase and that post-replicative ESCO2 degradation requires the
      complex as well as APC. Thus, we propose that the MCM complex couples ESCO2 with
      DNA replication and that the CUL4-DDB1-VPRBP complex promotes post-replicative
      ESCO2 degradation, presumably to suppress cohesion formation during mitosis.

PMID- 30100345
TI  - High-concentration iodinated contrast media for T1-weighted direct magnetic
      resonance arthrography.
AB  - AIM: To quantify in vitro the T1-weighted (T1W) expression of iodinated contrast
      media (CM), and to compare the in vivo performances of iodinated CM and
      gadolinium-based CM for T1W direct magnetic resonance imaging (MRI) arthrography.
      MATERIALS AND METHODS: An in vitro study on a 1.5 T MRI system was performed
      using Gd-DOTA, a mixture of iopromide and Gd-DOTA, and iopromide alone. The fat
      suppressed (FS) T1W signal intensities were measured and analysed. In an in vivo
      study, 15 normal rabbits were used to compare the expression of iopromide (370 mg
      iodine/ml), and the mixture of iopromide and diluted Gd-DOTA. In nine of the 15
      rabbits, extra-articular administrations of CM were performed to mimic the
      situation of CM leak. The rabbits were scanned on a 1.5 T MRI system, and the FS
      T1W sequence and an axial iterative decomposition of water and fat with echo
      asymmetry and least-squares estimation (IDEAL) T1W sequence were acquired. Signal
      intensities were measured and signal-to-noise ratios (SNR) were analysed.
      RESULTS: In the in vitro study, a higher SNR was noted in a higher concentration
      of iopromide, and the highest SNR of iopromide was 45.9% of that of Gd-DOTA. In
      the in vivo study, the iopromide and the mixture were well identified in all
      rabbits. The SNRs of the intra-articular and extra-articular iopromide and the
      mixture were significantly higher than the SNR of the muscles in the FS T1W
      images (all, p<0.01) and the IDEAL images (all, p<0.01). CONCLUSIONS: A high
      concentration iodinated CM can provide good imaging quality for T1W direct MRI
      arthrography, and may be an alternative option in certain clinical situations.

PMID- 30100346
TI  - Effects and mechanisms of sub-chronic exposure to copper nanoparticles on renal
      cytochrome P450 enzymes in rats.
AB  - Copper nanoparticles (Cu NPs) have widespread application because of their
      special physicochemical characteristics, however we need to more clearly study
      the toxicity mechanism of Cu NPs to ensure its safe use in pharmaceutical and
      animal feed. Thus, the aim of this study was to evaluate the effects and
      mechanisms of sub-chronic exposure to Cu NPs on renal CYP450 s of rats. In this
      study, we investigated the effects of Cu NPs on renal oxidative stress, cytokines
      and histopathology of rats. We found that Cu NPs (200 mg/kg) significantly
      disordered the function and structure of the kidney and caused a dose-dependent
      increase in oxidative stress and cytokines, which significantly decreased the
      levels of mRNA, protein, and activity of CYP450 s. Micro-coppers (Cu MPs) and Cu
      ions have similar effects, but their effects on CYP450 s were weaker than Cu NPs.
      The expression of nuclear receptors were inhibited and the expression of Akt,
      STAT3/5, CREB, p70S6K, NF-kappaB, P38 and ERK1/2 were activated when the
      inhibition effects of CYP450 s activity were observed in renal of rats.
      Therefore, we believe that Cu NPs can activate the STAT, NF-kappaB and MAPK
      signaling pathways to down-regulate the expression and activity of CYP450 s by
      inducing oxidative stress and inflammatory response in rat kidney.

PMID- 30100347
TI  - Mal d 1 and Bet v 1 sensitization pattern in children with Pollen Food Syndrome.

PMID- 30100348
TI  - Detecting and Imaging O-GlcNAc Sites Using Glycosyltransferases: A Systematic
      Approach to Study O-GlcNAc.
AB  - O-GlcNAcylation is a reversible serine/threonine glycosylation for regulating
      protein activity and availability inside cells. In a given protein, O
      GlcNAcylated and unoccupied O-linked beta-N-acetylglucosamine (O-GlcNAc) sites
      are referred to as closed and open sites, respectively. The balance between open
      and closed sites is believed to be dynamically regulated. In this report, closed
      sites are detected using in vitro incorporation of GalNAz by B3GALNT2, and open
      sites are detected by in vitro incorporation of GlcNAz by O-GlcNAc transferase
      (OGT), via click chemistry. For assessing total O-GlcNAc sites, a sample is O
      GlcNAcylated in vitro by OGT before detecting by B3GALNT2. The methods are
      demonstrated on purified recombinant proteins including CK2, AKT1, and PFKFB3,
      and cellular extracts of HEK cells. Through O-GlcNAc imaging, the modification
      degree of O-GlcNAc in nuclei of Chinese hamster ovary cells was estimated. The
      detection and imaging of both open and closed O-GlcNAc sites provide a systematic
      approach to study this important post-translational modification.

PMID- 30100351
TI  - Hyperglycemia crisis in head and neck cancer patients with platinum-based
      chemotherapy.
AB  - BACKGROUND: The development of a hyperglycemic crisis in platinum-based
      chemotherapy-treated head and neck cancer patients, such as hyperosmolar
      hyperglycemic state (HHS), has been reported. Hyperglycemic crises are associated
      with a high risk of comorbidity and may delay cancer treatment if not promptly
      managed. METHODS: This is a retrospective study using cancer registry data from a
      tertiary medical center. Head and neck cancer patients who had been treated with
      platinum-based chemotherapy from January 2014 to December 2015 were enrolled for
      review. Exclusion criteria included patients with a known history of type 2
      diabetes mellitus (DM). Characteristics of patients who developed type 2 DM after
      initiation of chemotherapy were compared with non-DM patients, following which
      the clinical course of the patients developing a hyperglycemic crisis were
      reviewed. RESULTS: A total of 185 patients were enrolled, of which seven patients
      (3.8%) had developed type 2 DM after initiation of platinum-based chemotherapy.
      No statistically significant differences in age, body mass index, sex, cancer
      subsite, cancer stage, or chemotherapy regimen were found when comparing new
      onset type 2 DM patients with the rest of the patients. Three patients developed
      diabetic ketoacidosis, HHS, or impending HHS after initiating chemotherapy
      treatment. The incidence of hyperglycemic crises was 3 out of 185 (1.6%) in this
      patient group. CONCLUSION: Hyperglycemic crisis after cisplatin may be
      underestimated and may lead to a life-threatening condition. We suggest regular
      weekly follow-ups of serum glucose level after platinum-based chemotherapy for
      early detection of hyperglycemia and prevention of a life-threatening crisis.

PMID- 30100349
TI  - Cryo-EM for Small Molecules Discovery, Design, Understanding, and Application.
AB  - We present a perspective of our view of the application of cryoelectron
      microscopy (cryo-EM) to structure-based drug design (SBDD). We discuss the basic
      needs and requirements for SBDD, the current state of cryo-EM, and the challenges
      that need to be overcome for this technique to reach its full potential in
      facilitating the process of drug discovery.

PMID- 30100352
TI  - Histological study of the protective role of ginger on piroxicam-induced liver
      toxicity in mice.
AB  - BACKGROUND: Piroxicam is a non-steroidal anti-inflammatory drug widely used in
      rheumatic diseases. It has analgesic and antipyretic activity, and is one of the
      drugs being introduced in clinical practice. Piroxicam-hepatotoxicity has been
      reported as one of its principal side effects. Several natural antioxidants were
      found to be effective against drug induced toxicity. Ginger is known by its
      antioxidant activities and hepatoprotective effects. The present study aimed at
      studying the protective effect of Ginger on Piroxicam-induced histopathological
      changes in livers of male mice. METHODS: Forty adult mice were randomly divided
      into 4 groups: Group I served as the control group. Group II received Ginger
      orally in a dose of 200 mg/kg per day for four weeks. Group III received
      Piroxicam intraperitoneally in a dose of 0.3 mg/kg per day for four weeks. Group
      IV received (Piroxicam + Ginger). At the end of the experiment, liver functions
      were estimated and then the liver was removed, and sampled for histopathological,
      immunohistochemistry and biochemical studies. RESULTS: Administration of ginger
      decreased elevated serum aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), and alkaline phosphatase (ALP) and immunoexpression of
      the proapoptotic protein (Bax), induced by piroxicam. It increased
      immunoexpression of the antiapoptotic protein (Bcl2). It also ameliorated the
      morphological changes induced by piroxicam. CONCLUSION: Piroxicam has toxic
      effects on the liver as indicated by biochemical, histological and
      immunohistochemical results. Ginger has protective effects against piroxicam
      hepatotoxicity by reducing serum marker enzymes, liver fibrosis and apoptosis.

PMID- 30100350
TI  - Small-Molecule TLR8 Antagonists via Structure-Based Rational Design.
AB  - Rational design of drug-like small-molecule ligands based on structural
      information of proteins remains a significant challenge in chemical biology. In
      particular, designs targeting protein-protein interfaces have met little success
      given the dynamic nature of the protein surfaces. Herein, we utilized the
      structure of a small-molecule ligand in complex with Toll-like receptor 8 (TLR8)
      as a model system due to TLR8's clinical relevance. Overactivation of TLR8 has
      been suggested to play a prominent role in the pathogenesis of various autoimmune
      diseases; however, there are still few small-molecule antagonists available, and
      our rational designs led to the discovery of six exceptionally potent compounds
      with ~picomolar IC50 values. Two X-ray crystallographic structures validated the
      contacts within the binding pocket. A variety of biological evaluations in
      cultured cell lines, human peripheral blood mononuclear cells, and splenocytes
      from human TLR8-transgenic mice further demonstrated these TLR8 inhibitors' high
      efficacy, suggesting strong therapeutic potential against autoimmune disorders.

PMID- 30100353
TI  - Early achievement of full donor chimerism after allogeneic hematopoietic stem
      cell transplantation predicts lower relapse risk in patients with acute
      lymphoblastic leukemia.
AB  - BACKGROUND: Acute lymphoblastic leukemia (ALL) remains one of the most difficult
      to-cure hematological malignancies. Allogeneic hematopoietic stem cell
      transplantation (HSCT) provides curative potential but a substantial proportion
      of patients eventually will relapse. It is unknown if there are any modifiable
      factors exists that could improve survival or predict relapse immediately after
      HSCT is unknown. The aim of this study was to explore whether achieving early
      (<30 days) full donor chimerism (FDC) could predict disease relapse after
      allogeneic HSCT in ALL patients. A second objective is to examine the impact of
      achieving early donor chimerism on survival. METHODS: This study retrospectively
      enrolled 55 ALL patients undergoing allogeneic HSCT during the 10-year period
      from 1999 to 2008. Analysis of short tandem repeats (STR) was used to determine
      donor chimerism, and was prospectively followed at the time of engraftment and on
      days 30. Patients with early treatment-related mortality (<30 days), without STR
      analysis, or who were lost to follow-up before FDC were excluded. Survival
      analyses were performed using Kaplan-Meier Methods. Cox proportional hazard
      analyses were performed for poor prognostic factors associated with overall
      survival (OS) and relapse-free survival (RFS). RESULTS: The general
      characteristics were comparable between patients with early donor chimerism (n =
      31) and those with late donor chimerism (n = 24). Survival analyses showed
      patients with early FDC had both lower probability of relapse (chi2 = 5.770, p =
      0.022) and longer RFS than those with late chimerism. The OS was not different
      according to the chimerism status on days 30. In the Cox proportional hazard
      analyses, early FDC is a significant factor predictive for longer RFS (HR =
      0.264, p = 0.010). CONCLUSION: Our results indicate that the achievement of early
      FDC within 30 days after allogenic HSCT can be used as a significant predictor of
      RFS. The results underscored the need to improve outcome in ALL patients with
      late FDC.

PMID- 30100354
TI  - Perception of fetal movement in the pregnant women.

PMID- 30100355
TI  - Comparison of cancer detection between 18- and 12-core prostate biopsy in Asian
      patients with prostate-specific antigen levels of 4-20 ng/mL.
AB  - BACKGROUND: Although prostate biopsy is an accepted option for cancer detection,
      there is little data regarding the clinical outcome of 18-core transrectal
      ultrasound (TRUS)-guided biopsy. This retrospective study compared cancer
      detection rates and biopsy complications between 12- and 18-core TRUS biopsy in
      Asian patients with prostate-specific antigen (PSA) levels between 4.0 and 20.0
      ng/mL. METHODS: In total, 1120 consecutive patients with PSA levels between 4.0
      and 20.0 ng/mL were divided into the 12-core (552 patients) and 18-core TRUS
      biopsy (568 patients) groups. The clinical outcomes of the 12- and 18-core TRUS
      biopsy groups were compared. Clinical outcomes were evaluated by comparing the
      prostate cancer detection rates and post-biopsy complication rates. RESULTS:
      There were no significant group differences in the PSA levels, but the mean age
      was significantly older in the 12-core biopsy group than in the 18-core biopsy
      group (mean age, 67.0 vs. 64.0 years, respectively; p = 0.001). The abnormal
      digital rectal examination rate was higher in the 12-core biopsy group than in
      the 18-core biopsy group (39.9% vs. 24.5%, respectively; p < 0.001). The prostate
      cancer detection rate was significantly higher in the 18-core group than in the
      12-core group [adjusted odds ratio: 2.75, 95% confidence interval = 2.04-3.01; p
      < 0.001], especially in patients with age >= 50 years, PSA < 10 and cancer
      clinical stage cT1. (p < 0.001). Moreover, in patients with prostate volumes >30
      mL or PSA densities <0.2, the prostate cancer detection rate was significantly
      higher in the 18-core group than in the 12-core group. There were no differences
      in the complication rates (e.g., urinary retention, hematuria, urinary tract
      infection, and urosepsis). CONCLUSION: In Asian patients with serum PSA levels
      between 4.0 and 20.0 ng/mL, 18-core biopsy was associated with superior clinical
      outcomes to those of 12-core biopsy for detecting prostate cancer.

PMID- 30100356
TI  - Chondroblastoma-like tumor of the skull in a patient with cardio-facio-cutaneous
      syndrome.
AB  - Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder characterized
      by craniofacial deformities and heterogeneous cardiac and cutaneous
      manifestations. The condition is caused by de novo activating mutations in one of
      four genes encoding proteins involved in the RAS-MAPK signaling pathway;
      specifically BRAF, MEK1, MEK2, or KRAS. Variable malignancies have been reported
      in patients with CFCS. Herein we report a chondroblastoma-like lesion of the
      skull in a 20-year-old man with a clinical diagnosis of CFCS and a long-standing
      history of medically intractable epilepsy. Patients with CFCS have previously
      been noted to have poorly-defined giant cell lesions and this may be one such
      example.

PMID- 30100357
TI  - KNL1 Binding to PP1 and Microtubules Is Mutually Exclusive.
AB  - The kinetochore scaffold 1 (KNL1) protein coordinates the spindle assembly
      checkpoint (SAC), a signaling pathway that delays chromosome segregation until
      all sister chromatids are properly attached to spindle microtubules. Recently,
      microtubules and protein phosphatase 1 (PP1), which both bind the N-terminal
      domain of KNL1, have emerged as regulators of the SAC; however, how these
      proteins interact to contribute to SAC signaling is unknown. Here, we use X-ray
      crystallography, nuclear magnetic resonance spectroscopy, and biochemical assays
      to show how KNL1 binds both PP1 and microtubules. Unexpectedly, we discovered
      that PP1 and microtubules bind KNL1 via overlapping binding sites. Further, we
      showed that Aurora B kinase phosphorylation results in distinct patterns of KNL1
      complex disruption. Finally, combining this data with co-sedimentation assays
      unequivocally demonstrated that microtubules and PP1 binding to KNL1 is mutually
      exclusive, with preferential formation of the KNL1:PP1 holoenzyme in the presence
      of PP1.

PMID- 30100359
TI  - Structural Basis for Selective Binding of Export Cargoes by Exportin-5.
AB  - In the nucleus, RanGTP binding to importin dissociates the cargo. On the other
      hand, RanGTP enables exportin to bind export cargo and form the export complex by
      each exportin's own cargo selection mechanism. Here, we present two X-ray
      structures for Exportin-5 (Exp-5) alone and Exp-5:RanGTP intermediate complex.
      The structure of Exp-5 adopts a ring-shaped closed conformation by C-terminal
      anchor residues 1,167-1,179, interacting with N-terminal heat repeats 4-9. The
      closed form of Exp-5 is important for the stability of the cargo-free state.
      Interaction between Exp-5 and RanGTP induces elimination of intramolecular
      contacts of the C-terminal anchor. A large movement of N-terminal 1-9th heat
      repeats and C-terminal 19-20th heat repeats creates an open space for RanGTP
      accommodation. Exp-5 in Exp-5:RanGTP and Exp-5:RanGTP:pre-miRNA adopts the same
      conformation. RanGTP binding to Exp-5 creates a selective molecular cage area for
      accepting its cargoes, such as small double-stranded RNAs, without conformational
      change in Exp-5:RanGTP.

PMID- 30100358
TI  - Structures of Hepatitis B Virus Core- and e-Antigen Immune Complexes Suggest
      Multi-point Inhibition.
AB  - Hepatitis B virus (HBV) is the leading cause of liver disease worldwide. While an
      adequate vaccine is available, current treatment options are limited, not highly
      effective, and associated with adverse effects, encouraging the development of
      alternative therapeutics. The HBV core gene encodes two different proteins: core,
      which forms the viral nucleocapsid, and pre-core, which serves as an immune
      modulator with multiple points of action. The two proteins mostly have the same
      sequence, although they differ at their N and C termini and in their dimeric
      arrangements. Previously, we engineered two human-framework antibody fragments
      (Fab/scFv) with nano- to picomolar affinities for both proteins. Here, by means
      of X-ray crystallography, analytical ultracentrifugation, and electron
      microscopy, we demonstrate that the antibodies have non-overlapping epitopes and
      effectively block biologically important assemblies of both proteins. These
      properties, together with the anticipated high tolerability and long half-lives
      of the antibodies, make them promising therapeutics.

PMID- 30100360
TI  - Management and prognosis of low-grade appendiceal mucinous neoplasms: A
      clinicopathologic analysis of 50 cases.
AB  - BACKGROUND: Low-grade appendiceal mucinous neoplasms (LAMN) are poorly understood
      lesions characterized by their potential to spread to the peritoneal cavity as
      pseudomyxoma peritonei (PMP). The purpose of this study was to investigate the
      clinical and pathologic features and management of these tumors. METHODS: This
      was a retrospective study of consecutive patients with LAMN who underwent surgery
      by a surgical team at the First Affiliated Hospital of China Medical University
      between 2005 and 2016. Subgroup analyses were performed for patients with PMP.
      RESULT: The study included 50 LAMN patients, 13 of them with PMP. There were no
      significant differences in age (p = 0.293) or gender (p = 0.196) at diagnosis
      between the two groups. There was no significant difference in their presentation
      (p = 0.700). Although 5 patients with PMP had perforation of the appendiceal
      mucinous, acute peritonitis was uncommon. Microscopic examination detected that
      PMP without any obvious perforation in tumors shown mucin and/or mucinous
      epithelium herniating into the appendiceal wall, or as islands within these
      tissues. The patients underwent appendectomy, caecectomy and right hemicolectomy
      according to the intraoperative situation. The median follow-up period was 53
      months (range 11-146 months). None of the patients developed clinical progression
      in either group during the follow-up period. CONCLUSION: The age of LAMN at
      presentation was almost 60 years (56.7) and there was no clear gender
      predilection. When LAMN was treated surgically with resection of the primary site
      in early stage disease or with pushing invasion, there was an excellent prognosis
      and expanded surgical procedures were unnecessary.

PMID- 30100361
TI  - Clinical significance of plasma D-dimer and fibrinogen in digestive cancer: A
      systematic review and meta-analysis.
AB  - BACKGROUND: Abnormalities of coagulation and fibrinolysis are frequently observed
      in cancer patients. Emerging data suggested that plasma D-dimer and fibrinogen
      levels correlated with tumor stage and prognosis in several cancer types. The aim
      of this study is to systematically review the prognostic value of plasma D-dimer
      and fibrinogen in digestive cancers. MATERIALS AND METHODS: We searched major
      database for manuscripts reporting the effect of pretreatment plasma d-dimer or
      fibrinogen on survival of digestive cancer patients. Revman5.3 and R were the
      software used for analysis. Pooled multivariable-adjusted hazard ratios (HR) for
      overall survival (OS) were calculated in all patients and many different subgroup
      analyses by stratifying on metastasis stage, tumor type, ethnicity, cutoff points
      and average age. RESULTS: 37 original studies were included for analysis.
      Increased levels of plasma D-dimer showed stronger association with worse OS than
      fibrinogen in digestive cancer (HR = 2.06, 95% CI 1.79-2.38; HR = 1.60, 95% CI
      1.44-1.79). The highest adverse impacts of elevated plasma D-dimer and fibrinogen
      on OS were revealed in colorectal cancer (HR = 2.32, 95% CI 1.89-2.85; HR = 2.20,
      95% CI 1.24-3.90). The negative prognostic effects of high plasma D-dimer
      enhanced in metastatic patients when compared with non-metastatic digestive
      cancer patients, while high plasma D-dimer was more predictive non-metastatic
      patients. CONCLUSIONS: Both of pretreatment plasma D-dimer and fibrinogen were
      robust predictors of poor survival in digestive cancer patients with different
      traits. Further studies are warranted to verify their roles on cancer prognosis.

PMID- 30100363
TI  - Chemosensory perception is specifically impaired in Parkinson's disease.
AB  - Patients with Parkinson's Disease (PD) exhibit a considerably diminished sense of
      smell. The olfactory system is intimately connected to the trigeminal system,
      responsible for the perception of sensations such as freshness, warmth or
      piquancy in odorants. Usually, olfactory impairment is associated with a similar
      reduction of trigeminal sensitivity. A recent study suggests that the trigeminal
      system is not affected in patients with PD. To test this, we evaluated perception
      of mixed olfactory/trigeminal stimuli in 23 patients with idiopathic PD and
      compared them to 22 healthy matched controls. More specifically, we evaluated the
      trigeminal dimensions of coolness, warmth and piquancy and the olfactory
      dimensions of pleasantness, familiarity and edibility of 10 mixed
      olfactory/trigeminal odorants using Likert scale. We show that PD patients
      perceive trigeminal sensations of coolness, warmth, and piquancy of odorants
      equally well as controls, as opposed to olfactory dimensions that are perceived
      significantly less compared to controls (p < 0.001). Moreover, Chi-square Tests
      show that equal number of participants in both groups perceive the trigeminal
      dimensions of odorants. Thus, we provide further evidence that the trigeminal
      system, as opposed to the olfactory system, is not impaired in PD patients
      reflecting a specific pattern of chemosensory impairment in PD.

PMID- 30100364
TI  - Field synopsis and systematic meta-analyses of genetic association studies in
      isolated dystonia.
AB  - BACKGROUND AND OBJECTIVES: Dystonia is a genetically complex disease with both
      monogenic and polygenic causes. For the latter, numerous genetic associations
      studies have been performed with largely inconsistent results. The aim of this
      study was to perform a field synopsis including systematic meta-analyses of
      genetic association studies in isolated dystonia. METHODS: For the field synopsis
      we systematically screened and scrutinized the published literature using NCBI's
      PubMed database. For genetic variants with sufficient information in at least two
      independent datasets, random-effects meta-analyses were performed, including meta
      analyses stratified by ethnic descent and dystonia subtypes. RESULTS: A total of
      3575 articles were identified and scrutinized resulting in the inclusion of 42
      independent publications allowing 134 meta-analyses on 45 variants across 17
      genes. While our meta-analyses pinpointed several association signals with
      variants in TOR1A, DRD1, and ARSG, no single variant displayed compelling
      association with dystonia in the available data. CONCLUSIONS: Our study provides
      an up-to-date summary of the status of dystonia genetic association studies.
      Additional large-scale studies are needed to better understand the genetic causes
      of isolated dystonia.

PMID- 30100365
TI  - Mendel and urate: Acid test or random noise?

PMID- 30100362
TI  - Nipple-Sparing Mastectomy: Reliability of sub-areolar sampling and frozen section
      in predicting occult nipple involvement in breast cancer patients.
AB  - INTRODUCTION: The oncological safety of nipple-areolar complex (NAC) preservation
      is a concern in the mastectomies performed for cancer indication. The detection
      of tumor cells during the intraoperative frozen section examination (IE) of sub
      areolar/nipple tissue (SAT) leads to the removal of NAC, but frequently the final
      histology of the nipple is negative for malignancy. This study aims to evaluate
      the accuracy of SAT examination in predicting occult NAC involvement in case of
      Nipple-Sparing Mastectomy (NSM). METHODS: The study includes 76 NSM. We evaluated
      the concordance between histopathologic features of frozen and paraffin-embedded
      SAT sections. Moreover, we examined the "true margin" (TM), defined as the
      measurement of the distance between the tumor margin and the edge of the SAT. A
      margin >1 mm was considered negative. RESULTS: In 26/76 cases the IE of the SAT
      was positive. At the final histology, the NAC was negative in 57.7% of cases. The
      concordance between frozen and paraffin section examination of the SAT was 92.1%.
      The three false-positives were low-grade DCIS at the IE, and negative or DIN1a on
      permanent section. A negative TM seems to predict for a negative NAC (6/6).
      CONCLUSIONS: The detection of a low-grade DCIS at the IE of the SAT may not be
      confirmed at the permanent section examination; we recommend caution in removing
      the NAC in these cases. The evaluation of the TM may improve the accuracy of SAT
      analysis in predicting occult NAC involvement; in our series, a TM wider than 1
      mm correlates with a negative NAC.

PMID- 30100367
TI  - Emerging Models of Providing Oncology Palliative Care.
AB  - OBJECTIVE: To describe palliative care integration into oncology, including
      several models that facilitate this integration, important considerations when
      initiating a program, special oncologic populations that would benefit from
      palliative care, and challenges to consider. DATA SOURCES: Palliative care and
      oncology literature over the past decade. CONCLUSION: Multiple models exist to
      facilitate the integration of palliative care based on the needs of the providers
      or payers. There are several special populations that would benefit from early
      integration of palliative care. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a
      critical role in identifying patients, providing early primary palliative care,
      and facilitating collaborative relationships with and referring to specialist
      palliative care.

PMID- 30100369
TI  - Evidence-based Management of Cancer Pain.
AB  - OBJECTIVE: To provide a brief review of common palliative care practices in the
      assessment and management of cancer pain for practicing oncology nurses. DATA
      SOURCES: Published literature as indexed in Medline, relevant guideline
      documents, textbooks, and clinical experience. CONCLUSION: All persons with
      cancer should undergo a comprehensive pain assessment, using validated
      instruments when possible, and receive expert-guided cancer pain therapy.
      Specialist palliative care consultation should be engaged as needed to provide an
      extra layer of support. IMPLICATIONS FOR NURSING PRACTICE: By better
      understanding cancer pain assessment and management strategies, nurses will be
      best equipped to meet the needs of patients and families.

PMID- 30100366
TI  - Advance Care Planning and End-of-Life Decision Making for Patients with Cancer.
AB  - OBJECTIVE: To highlight the importance, challenges, and evolution of advance care
      planning for patients with cancer. DATA SOURCES: Peer-reviewed journal articles
      and clinical guidelines. CONCLUSION: Advance care planning is fundamental to
      support the personhood of patients with advanced cancer. Patients must be
      encouraged by physicians and nurses to articulate what matters and provides
      meaning to them as they live, cope, and receive treatment for their cancer.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses can facilitate advance care planning
      and primary palliative care, to support patients and families to make informed
      and value-concordant decisions regarding cancer and end-of-life treatments.

PMID- 30100370
TI  - Closing the Gap on Pediatric Palliative Oncology Disparities.
AB  - OBJECTIVES: To describe pediatric palliative care (PPC) in pediatric oncology,
      the importance of PPC for pediatric oncology patients, disparities within
      pediatric palliative oncology, innovative strategies for improving PPC access in
      underserved populations, and implications for oncology nursing practice. DATA
      SOURCES: Published pediatric oncology and palliative peer-reviewed articles and
      guidance documents. CONCLUSION: Disparities exist within pediatric palliative
      oncology. There is much work needed to improve the reach and quality of PPC for
      pediatric oncology patients, especially those from underserved populations.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses serve a critical role in advocating for
      PPC for seriously ill pediatric cancer patients and their families.

PMID- 30100368
TI  - Communicating with Patients and Families Around Difficult Topics in Cancer Care
      Using the COMFORT Communication Curriculum.
AB  - OBJECTIVES: To examine nurse communication in cancer care and offer communication
      strategies for quality palliative care nursing. DATA SOURCES: Communication
      strategies offered are based on the COMFORT Communication curriculum, an evidence
      based communication training program. CONCLUSION: Whole-patient assessment, a
      major component of palliative care, involves communication that includes
      eliciting the patient's story, addressing health literacy needs, being mindful of
      burnout, and relating to the patient and family. IMPLICATIONS FOR NURSING
      PRACTICE: Quality communication skills are essential to oncology nursing,
      especially given their vital role in cancer care.

PMID- 30100371
TI  - Introduction.

PMID- 30100372
TI  - Psychological Symptoms in Advanced Cancer.
AB  - OBJECTIVES: To discuss psychological symptoms among patients with advanced
      cancer, assessment of psychological symptoms, and evidence-based strategies to
      manage psychological symptoms. DATA SOURCES: Current cancer-care guidelines and
      journal articles. CONCLUSION: Psychological symptoms are prevalent among patients
      with advanced cancer and may not be evident without appropriate screening.
      Distressed patients may not meet criteria for a full clinical psychiatric
      diagnosis, but may still benefit from interventions to improve quality of life.
      IMPLICATIONS FOR NURSING PRACTICE: Nurses can improve the lives of patients by
      assessing for psychological symptoms; providing appropriate referrals, treatment,
      and/or follow-up; and recommending integrative methods for psychological symptom
      self-management.

PMID- 30100373
TI  - A rare cause of type 1 complex regional pain syndrome: Osteoblastoma of the
      talus.
AB  - We report a 14-year-old boy who presented with pain in the left foot and ankle
      for about 9 months. The clinical symptoms of the patient suggested complex
      regional pain syndrome (CRPS). The radiographs and magnetic resonance imaging
      studies ravealed a bone tumor in the talus, consistent with an osteoblastoma. The
      patient underwent operative treatment with curettage and grafting. The complaints
      of the patient completely resolved by 6 months after surgery, and there was no
      recurrence at the postoperative 23th month follow-up.

PMID- 30100374
TI  - Restoration of CD3+CD56+ cell level improves skin lesions in severe psoriasis: A
      pilot clinical study of adoptive immunotherapy for patients with psoriasis using
      autologous cytokine-induced killer cells.
AB  - Psoriasis is a chronic inflammatory skin disorder mediated by the cells and
      molecules of both the innate and adaptive immune systems. Autologous cytokine
      induced killer (CIK) cell infusion is considered an effective and safe cancer
      treatment and is licensed for this use in China. Accumulated evidence indicating
      that CD3+CD56+ cells are significantly decreased in psoriatic patients prompted
      us to investigate if the restoration of CD3+CD56+ cells may be beneficial for
      psoriatic patients. We designed a clinical trial for psoriasis treatment that
      involved CIK cell infusion because CIK cells include a large amount of CD3+CD56+
      T cells (NCT01894373 at www.clinicaltrials.gov). Six patients with severe
      psoriasis were initially enrolled, and four of them exhibited markedly lower
      levels of CD3+CD56+ cells in their peripheral blood (PB) relative to healthy
      donors. CIK cell infusion-associated toxicity was not observed in any infusion.
      The percentage of CD3+CD56+ cells in the PB markedly increased and the psoriasis
      area and severity index (PASI) synchronously decreased in four patients with
      lower CD3+CD56+ cell contents, and two of them obtained a more than 4-month
      PASI75 after completing a four-cycle treatment. However, a decrease in the
      CD3+CD56+ cells was observed concomitantly with disease recurrence after short
      term amelioration. In contrast, no obvious improvement was observed in the two
      patients with nearly normal CD3+CD56+ cells in the PB before treatment. These
      observations suggest that the normalization of the CD3+CD56+ cell level may
      improve the skin lesions of severe psoriasis and warrant further clinical trials
      for severe psoriasis using repeated CIK adoptive immunotherapy.

PMID- 30100376
TI  - Problems in Medicare hospice provision.

PMID- 30100377
TI  - CCR4-targeted therapy in cutaneous T-cell lymphoma.

PMID- 30100378
TI  - HPV status and oesophageal adenocarcinoma.

PMID- 30100380
TI  - Treatment of platinum refractory or resistant ovarian cancer.

PMID- 30100375
TI  - Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma
      (MAVORIC): an international, open-label, randomised, controlled phase 3 trial.
AB  - BACKGROUND: Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with
      substantial morbidity and mortality in advanced disease stages. We compared the
      efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C
      chemokine receptor 4, with vorinostat in patients with previously treated
      cutaneous T-cell lymphoma. METHODS: In this open-label, international, phase 3,
      randomised controlled trial, we recruited patients with relapsed or refractory
      mycosis fungoides or Sezary syndrome at 61 medical centres in the USA, Denmark,
      France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and
      Australia. Eligible patients were aged at least 18 years (in Japan, >=20 years),
      had failed (for progression or toxicity as assessed by the principal
      investigator) at least one previous systemic therapy, and had an Eastern
      Cooperative Oncology Group performance score of 1 or less and adequate
      haematological, hepatic, and renal function. Patients were randomly assigned
      (1:1) using an interactive voice web response system to mogamulizumab (1.0 mg/kg
      intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15
      of subsequent cycles) or vorinostat (400 mg daily). Stratification was by
      cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sezary syndrome) and
      disease stage (IB-II vs III-IV). Since this study was open label, patients and
      investigators were not masked to treatment assignment. The primary endpoint was
      progression-free survival by investigator assessment in the intention-to-treat
      population. Patients who received one or more doses of study drug were included
      in the safety analyses. This study is ongoing, and enrolment is complete. This
      trial was registered with ClinicalTrials.gov, number NCT01728805. FINDINGS:
      Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly
      assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the
      intention-to-treat population. Two patients randomly assigned to mogamulizumab
      withdrew consent before receiving study treatment; thus, 370 patients were
      included in the safety population. Mogamulizumab therapy resulted in superior
      investigator-assessed progression-free survival compared with vorinostat therapy
      (median 7.7 months [95% CI 5.7-10.3] in the mogamulizumab group vs 3.1 months
      [2.9-4.1] in the vorinostat group; hazard ratio 0.53, 95% CI 0.41-0.69;
      stratified log-rank p<0.0001). Grade 3-4 adverse events of any cause were
      reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of
      186 patients in the vorinostat group. The most common serious adverse events of
      any cause were pyrexia in eight (4%) patients and cellulitis in five (3%)
      patients in the mogamulizumab group; and cellulitis in six (3%) patients,
      pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the
      vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due
      to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with
      vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were
      considered treatment-related. INTERPRETATION: Mogamulizumab significantly
      prolonged progression-free survival compared with vorinostat, and could provide a
      new, effective treatment for patients with mycosis fungoides and, importantly,
      for Sezary syndrome, a subtype that represents a major therapeutic challenge in
      cutaneous T-cell lymphoma. FUNDING: Kyowa Kirin.

PMID- 30100379
TI  - Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant
      ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo
      controlled, phase 2 trial.
AB  - BACKGROUND: Antiangiogenic therapy has known activity in ovarian cancer. The
      investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase
      inhibitor sorafenib combined with topotecan and continued as maintenance therapy
      for platinum-resistant or platinum-refractory ovarian cancer. METHODS: We did a
      multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20
      sites in Germany. Patients (>=18 years) with platinum-resistant ovarian cancer
      previously treated with two or fewer chemotherapy lines for recurrent disease
      were stratified (first vs later relapse) in block sizes of four and randomly
      assigned (1:1) using a web-generated response system to topotecan (1.25 mg/m2 on
      days 1-5) plus either oral sorafenib 400 mg or placebo twice daily on days 6-15,
      repeated every 21 days for six cycles, followed by daily maintenance sorafenib or
      placebo for up to 1 year in patients without progression. Investigators and
      patients were masked to allocation of sorafenib or placebo; topotecan treatment
      was open label. The primary endpoint was investigator-assessed progression-free
      survival, analysed in all patients who received at least one dose of study drug.
      This completed trial is registered with ClinicalTrials.gov, number NCT01047891.
      FINDINGS: Between Jan 18, 2010, and Sept 19, 2013, 185 patients were enrolled,
      174 of whom were randomly assigned: 85 to sorafenib and 89 to placebo. Two
      patients in the sorafenib group had serious adverse events before treatment and
      were excluded from analyses. 83 patients in the sorafenib group and 89 in the
      placebo group started treatment. Progression-free survival was significantly
      improved with sorafenib versus placebo (hazard ratio 0.60, 95% CI 0.43-0.83;
      p=0.0018). Median progression-free survival was 6.7 months (95% CI 5.8-7.6) with
      sorafenib versus 4.4 months (3.7-5.0) with placebo. The most common grade 3-4
      adverse events were leucopenia (57 [69%] of 83 patients in the sorafenib group vs
      47 [53%] of 89 in the placebo group), neutropenia (46 [55%] vs 48 [54%]), and
      thrombocytopenia (23 [28%] vs 20 [22%]). Serious adverse events occurred in 49
      (59%) of 83 sorafenib-treated patients and 45 (51%) of 89 placebo-treated
      patients. Of these, events were fatal in four patients (5%) in the sorafenib
      group (dyspnoea and poor general condition, septic shock, ascites and dyspnoea,
      and sigma perforation) and seven (8%) in the placebo group (pulmonary embolism in
      two patients, disease progression in two patients, and one case each of sepsis
      with fever, pleural effusion, and tumour cachexia). Sorafenib was associated with
      increased incidences of grade 3 hand-foot skin reaction (three [13%] vs 0
      patients) and grade 2 alopecia (24 [29%] vs 12 [13%]). INTERPRETATION: Sorafenib,
      when given orally in combination with topotecan and continued as maintenance
      therapy, showed a statistically and clinically significant improvement in
      progression-free survival in women with platinum-resistant ovarian cancer. These
      encouraging results support the crucial role of antiangiogenesis as the treatment
      backbone in combination with chemotherapy, making this approach attractive for
      further assessment with other targeted strategies. FUNDING: Bayer, Amgen, and
      GlaxoSmithKline.

PMID- 30100381
TI  - Upper-eyelid weight implants for patients with lagophthalmos-comparison of rigid
      and flexible implants.
AB  - INTRODUCTION: For treatment of lagophthalmos, metallic weight implants can be
      inserted in the upper eyelid to aid eyelid closure. Rigid and flexible implants
      are available. The objective of this study was to investigate the effect of
      implant type and patient variables on the survival of lid load implants.
      MATERIALS AND METHODS: Forty-four patients with lagophthalmos were recruited to
      undergo upper-eyelid weight implantation. The predictor variable was type of
      implant inserted (rigid or flexible). The outcome variable was survival of the
      inserted implant (survival or extrusion). Other study variables were demographic
      data (age, gender), implant features (material, weight), and other conditions,
      such as history of radiation. An NMLE test was used to compare implant survival,
      depending on implant type (flexible versus rigid). Other variables were analysed
      by use of a chi2 test. RESULTS: Forty-four participants were recruited, 29 female
      (65.9%) and 15 male (34.1%). Forty-six implants (23 rigid implants, 50.0%; 23
      flexible implants, 50.0%) were inserted (bilateral implantation in two patients).
      The average weight of implants used was 1.76 g (range 1.4-2.2 g). One to two
      years after surgery, average vertical aperture (eyelid gap) for the closed eye
      was 0.65 mm (range 0-4 mm). Incidence of extrusion was 15.2% (one in the rigid
      implant group, 2.2%; six in the flexible implant group, 13.0%). Incidence of
      extrusion was significantly higher for flexible implants than for rigid implants
      (p = 0.0273). CONCLUSIONS: The study results suggest that flexible implants are
      more likely to perforate the skin. The assumed advantages of the expensive chain
      lid weight must, therefore, be re-evaluated.

PMID- 30100382
TI  - Promotor hypermethylated genes: Prospective diagnostic biomarkers in oral
      cancerogenesis.
AB  - : The advancements in epigenetics of oral squamous cell carcinoma (OSCC), are
      made in regard to DNA hypermethylation of MGMT, DAPK, ECAD (E-cadherin) and p16,
      as an important component of oral carcinogenesis and new potential biomarkers in
      molecular diagnostic strategies. The objective of the study was to evaluate the
      methylation status of the proposed genes and their possible role in the tumor
      genesis and diagnosis of OSCC. MATERIALS AND METHODS: From sixty surgically
      treated and molecularly analyzed patients, we obtained three groups of bioptical
      materials: tumor, normal contralateral and healthy tissues. Comparison of the
      frequencies of DNA methylation for all transcripts was utilized to validated
      their potential role in the cancerogenesis and detection of OSCC. RESULTS: The
      most often methylated genes in the tumor samples were ECAD, MGMT, DAPK followed
      by p16 genes (90% vs 75% vs 75% vs 52,5%), respectively. We observed frequent
      methylated genes in contralateral mucosa and consistently unmethylated- 0% in
      healthy samples. ECAD methylated genes showed the highest sensitivity for
      diagnosing OSCC in tumor and contralateral tissues (90% and 89,7% respectively,
      with a specificity of 100%). CONCLUSION: ECAD and MGMT have tumor-specific
      signatures and can be considered as potential noninvasive diagnostic biomarkers
      in OSCC.

PMID- 30100383
TI  - Midfacial growth and dental arch relationships in bilateral cleft palate
      following secondary alveolar bone grafting and orthodontic intervention: Factors
      predicting a Le Fort I osteotomy at age 18.
AB  - OBJECTIVE: To evaluate midfacial growth and dental arch relationships in patients
      treated for bilateral cleft lip and palate (BCLP). MATERIALS AND METHODS: Data
      were collected from all patients with BCLP treated at our hospital between 2004
      and 2014, with or without premaxillary osteotomy (PO). Dental casts for pre
      secondary alveolar bone grafting with PO (SABG + PO) and end-point dental casts
      were analyzed using the BAURU yardstick scoring system. Pre-SABG + PO, post-SABG
      + PO, and end-point SABG + PO lateral cephalograms were analyzed. The correlation
      between both scoring systems was calculated. RESULTS: There were no significant
      differences between the BAURU scores for centers in a previous study and those
      collected here. A negative correlation was found between the pre-SABG + PO ANB
      (Angle between A-point, Nasion and B-point) angle and pre-SABG + PO BAURU scores
      (R = -0.58; p = 0.000), the long-term post-SABG + PO ANB and mean end-point BAURU
      (R = -0.50; p = 0.000), and the pre-SABG + PO ANB and mean end-point BAURU (R = 
      0.51; p = 0.000). CONCLUSION: We found no significant difference between pre-SABG
      + PO and end-point BAURU scores. There was a decrease in the SNA (Angle between
      Sella, Nasion and A-point) and ANB angle over time, indicating delayed growth of
      the maxilla. We found a negative correlation between the pre-SABG ANB and end
      point BAURU scores. Pre-SABG ANB can be used to predict the need for Le Fort I
      osteotomy at age 18.

PMID- 30100384
TI  - Morphometric analysis of arcuate eminence: A distinctive landmark for middle
      cranial fossa approach.
AB  - BACKGROUND: The arcuate eminence (AE) is a bony prominence on the middle fossa
      plate of the temporal bone, hypothesized to be variably associated with superior
      semicircular canal (SSC) relief, temporal lobe sulcus, and subjacent air cells.
      We present various morphometric parameters of the AE, as seen using a middle
      fossa approach. MATERIALS AND METHODS: The study used 18 formalin-preserved
      cadaveric human temporal bones. Various morphological and morphometric parameters
      pertaining to topographic orientation of the AE in relation to surrounding
      landmarks used in a middle mossa approach were noted, before and after
      microdissection of the AE under a Leica M320 F12 microscope, using otologic
      microdrills and suction irrigation. The morphometric parameters were analyzed
      using ImageJ 1.46r software. RESULTS: The overall incidence of AE was 83% (n =
      15/18). The most common shape and pattern noted were linear (53.3%, 8/15) and
      dual arc (46.7%, 7/15), respectively. Mean angle between the AE and SSC was 19
      degrees , with a standard deviation of 15 degrees  and a range of 2-49 degrees .
      The AE overlapped the SSC in 40% (6/15) of bones, and did not correspond to the
      SSC in 7% of cases. A partially overlapping positional correspondence was noted
      in 53.3% (8/15). CONCLUSION: When present, the AE corresponds to the SSC in 40%
      of cases, but it can serve as a rough guide to the SSC in up to 93% of cases.
      Surgeons need to be familiar with the varying morphology of AEs in order to
      execute a rapid and safe dissection during middle fossa approaches.

PMID- 30100385
TI  - Rhipicephalus sanguineus (Latreille, 1806): Neotype designation, morphological re
      description of all parasitic stages and molecular characterization.
AB  - The aims of this work were to re-describe all parasitic stages of Rhipicephalus
      sanguineus sensu stricto, to select and deposit a neotype, and to characterize
      some of its diagnostic molecular traits. A male of R. sanguineus s.s. collected
      in Montpellier, France, was designated as neotype. The diagnostic characters
      unique to the male of R. sanguineus s.s. are: spiracular plate elongated and
      subtriangular in shape with a dorsal prolongation narrow and usually visible
      dorsally, with the dorsal prolongation narrower than the width of the adjacent
      festoon; punctations of the scutum moderate in number and unequal in size;
      marginal groove conspicuous, deep and punctate; posteromedian groove distinct and
      elongated, and posterolateral grooves often sub-circular, shorter than
      posteromedian groove; adanal plates long, wide, and subtriangular in shape, with
      a clear concavity in its inner margin and posterior margin broadly rounded or
      truncated; accessory adanal plates with the posterior end pointed, narrower than
      the width of adjacent festoon. The female of R. sanguineus s.s. can be diagnosed
      by a combination of broadly U-shaped genital aperture, spiracular plate with a
      narrow dorsal prolongation visible dorsally, basis capituli hexagonal with broad
      lateral angles, and scutum barely longer than broad with posterior margin sinuous
      and punctations moderate in number and unequal in size, larger and more numerous
      along cervical fields. The nymph has a basis capituli sub-triangular dorsally
      with lateral angles slightly curved and presence of ventral processes, scutum
      approximately as long as broad with lateral margins nearly straights, posterior
      margin broadly rounded, and cervical grooves short and sigmoid in shape extending
      posteriorly to the level of the eyes. The larva is characterized by basis
      capituli broader than long with lateral angles short and slightly curved and with
      posterior margin slightly convex, cervical grooves short, shallow and
      subparallel, and scutum almost twice broader than long. The phylogenetic analysis
      of DNA sequences support R. sanguineus s.s. as a well-defined taxon when compared
      with other species of the R. sanguineus group: R. turanicus s.s., R. camicasi, R.
      guilhoni, R. sulcatus, R. pusillus, R. rossicus and R. leporis. Molecularly R.
      sanguineus s.s. also encompasses the so-called "temperate lineage" from the New
      World (Argentina, southern Brazil, Chile, Uruguay, and USA). The evidence
      currently available supports the presence of R. sanguineus s.s. in Europe
      (France, Italy, Spain, Switzerland and Portugal) and America (Argentina, Brazil,
      Chile, Uruguay and U.S.A.), but further studies are needed to determine the exact
      geographic range of this taxon.

PMID- 30100386
TI  - Molecular characterization of Haemaphysalis longicornis-borne rickettsiae,
      Republic of Korea and China.
AB  - Haemaphysalis longicornis, the cattle tick or bush tick, has an extended
      distribution throughout Asia and the Pacific region, including China, Russia, the
      Republic of Korea (ROK), Japan, Australia, New Zealand, and the South Pacific
      islands. It is an obligate ectoparasite found commonly on medium to large sized
      wild and domestic animals, with humans as an accidental host. Haemaphysalis
      longicornis transmits a number of pathogens, including severe fever with
      thrombocytopenia syndrome and tick-borne encephalitis viruses, bacteria,
      helminths, and protozoans, that impact on veterinary (wild and domestic animals)
      and human health. Surveys of rickettsial pathogens associated with H. longicornis
      from China, the ROK, and Japan have resulted in the discovery of more than 35
      incompletely characterized molecular isolates of Rickettsia. In response to the
      increased global threat of tick-borne rickettsial diseases, H. longicornis
      collected in the ROK and China were assessed in our laboratory and two additional
      Rickettsia spp. isolates (ROK-HL727 and XinXian HL9) were identified. These
      agents were fully characterized by multilocus sequence typing using partial gene
      fragment sequences of rrs, gltA, ompA, ompB, and sca4. Phylogenetic comparisons
      of these Rickettsia isolates with known Rickettsia species and other molecular
      isolates identified from H. longicornis were performed to better understand their
      interrelationships. Phylogenetic analysis of the sequences from these 5 gene
      fragments showed that ROK-HL727 was closely related to rickettsial isolates of H.
      longicornis previously reported from China, the ROK and Japan, but distinct from
      any currently recognized Rickettsia species. It therefore qualifies genetically
      as a new species, introduced herein as Candidatus Rickettsia longicornii. The
      XinXian-HL9 isolate detected from China was determined to be genetically similar
      to the human pathogen Rickettsia heilongjiangensis. People living and working in
      areas where H. longicornis is endemic should be aware of the potential for
      rickettsial diseases.

PMID- 30100388
TI  - Microbiocidal characterization of a novel povidone-iodine based rigid contact
      lens disinfecting solution.
AB  - This study investigated the efficacy of a novel povidone-iodine based
      disinfection solution for rigid gas permeable (RGP) lenses compared to three
      other currently available multipurpose and hydrogen peroxide solutions.
      Bactericidal and fungicidal activities were assessed using ISO 14729 reference
      methods, whilst amoebicidal properties were evaluated using an automated
      viability counter. All solutions were also assessed for long term storage
      stability over a 3-month period. The FDA guidelines were adequately achieved by
      all solutions tested and 3-month storage did not affect their activity against
      bacterial and fungal agents. Activity against Acanthamoeba castellani
      trophozoites reached 1-log reduction for the povidone-iodine solution and
      approached this level for the remaining solutions. Activity against cysts was
      somewhat reduced and ranged from 78 to 86% reduction in viability. A povidone
      iodine based solution, which may offer advantages as resistance to this agent has
      not been demonstrated and it lacks toxicity, provided equivalent antimicrobial
      activity to other RGP solutions.

PMID- 30100387
TI  - 'One Health' solutions for ticks and tick-borne diseases, and rickettsial
      pathogens of humans, domestic animals and wildlife.

PMID- 30100389
TI  - Historical biological essentialism.

PMID- 30100390
TI  - Genetic analysis of 26 Y-STR loci in Han population from Leshan, Southwest China.

PMID- 30100391
TI  - Long-term survival after post-hepatectomy liver failure for colorectal liver
      metastases.
AB  - BACKGROUND: While post-hepatectomy liver failure (PHLF) accurately predicts short
      term mortality, its role in prognosticating long-term overall survival (OS)
      remains unclear. METHODS: Patients who underwent hepatectomy for colorectal liver
      metastases (CRLM) after portal vein embolization during 1999-2015 were evaluated
      retrospectively. PHLF was defined per International Study Group of Liver Surgery
      (ISGLS) criteria and as PeakBil >7 mg/dl. Survival was analyzed using log-rank
      statistic and Cox regression; patient mortality within 90 days was excluded.
      RESULTS: Of 175 patients, 68 (39%) had PHLF according to ISGLS criteria,
      including 40 (23%) with ISGLS grade B/C, and 14 (8%) had PeakBil >7 mg/dl.
      Patients with PeakBil >7 mg/dl had significantly worse OS than patients without
      PHLF (median OS, 16 vs 58 months, p = 0.001). Patients with ISGLS defined PHLF (p
      = 0.251) and patients with ISGLS grade B/C PHLF (p = 0.220) did not have worse OS
      than patients without PHLF. CONCLUSION: Peak bilirubin >7 mg/dl impacts on long
      term survival after hepatectomy for CRLM and is a better predictor of long-term
      survival than ISGLS-defined PHLF.

PMID- 30100392
TI  - Unexpected intestinal bypass.

PMID- 30100394
TI  - Colistin resistance, beyond the current knowledge.

PMID- 30100393
TI  - ITGAE Defines CD8+ Tumor-Infiltrating Lymphocytes Predicting a better Prognostic
      Survival in Colorectal Cancer.
AB  - BACKGROUND: Tumor-infiltrating lymphocytes (TIL) in colorectal tumor tissue are
      significantly correlated with a favorable prognosis, such as CD8+ lymphocytes,
      which are also called tumor-reactive lymphocytes. However, not all tumor
      infiltrating T cells confer benefit to patients. Therefore, it is of substantial
      benefit to identify a biomarker to demarcate these tumor-reactive lymphocytes.
      METHODS: We investigated whether ITGAE could be used to discriminate reactive
      CD8+ lymphocytes in colorectal cancer (CRC). TCGA colorectal cancer data sets (n1
      = 492, n2 = 386) and FUSCC set (n3 = 276) were used in this study. Further
      phenotyping of ITGAE+ cells and the mechanistic basis were investigated.
      FINDINGS: In the training and testing sets from TCGA, ITGAE expression, which is
      strongly correlated with cytotoxic T cell markers (CD8/CD3/PD1), independently
      predicted longer disease-free survival (DFS) and overall survival (OS). In line
      with this, the association between ITGAE+ lymphocytes and survival has been
      confirmed in the FUSCC cohort for validation (P = .026). ITGAE + cells in the
      series always co-stained with CD8 were preferentially located in the tumor.
      Interestingly, ITGAE+ lymphocytes tended to associate with the epithelial
      mesenchymal transition (EMT) with decreased Snail and increased E-cadherin
      expression accompanied. Finally, gene set enrichment analysis showed that immune
      activation was significantly enriched in the high ITGAE+ TIL group, accompanied
      by enriched EMT-related pathways. INTERPRETATION: Because of the specified
      expression of tumor-reactive CD8+ T-cells, ITGAE may be a promising biomarker for
      the rapid identification of immune infiltration in CRC.

PMID- 30100395
TI  - A novel mechanism of SRRM4 in promoting neuroendocrine prostate cancer
      development via a pluripotency gene network.
AB  - BACKGROUND: Prostate adenocarcinoma (AdPC) cells can undergo lineage switching to
      neuroendocrine cells and develop into therapy-resistant neuroendocrine prostate
      cancer (NEPC). While genomic/epigenetic alterations are shown to induce
      neuroendocrine differentiation via an intermediate stem-like state, RNA splicing
      factor SRRM4 can transform AdPC cells into NEPC xenografts through a direct
      neuroendocrine transdifferentiation mechanism. Whether SRRM4 can also regulate a
      stem-cell gene network for NEPC development remains unclear. METHODS: Multiple
      AdPC cell models were transduced by lentiviral vectors encoding SRRM4. SRRM4
      mediated RNA splicing and neuroendocrine differentiation of cells and xenografts
      were determined by qPCR, immunoblotting, and immunohistochemistry. Cell
      morphology, proliferation, and colony formation rates were also studied. SRRM4
      transcriptome in the DU145 cell model was profiled by AmpliSeq and analyzed by
      gene enrichment studies. FINDINGS: SRRM4 induces an overall NEPC-specific RNA
      splicing program in multiple cell models but creates heterogeneous
      transcriptomes. SRRM4-transduced DU145 cells present the most dramatic neuronal
      morphological changes, accelerated cell proliferation, and enhanced resistance to
      apoptosis. The derived xenografts show classic phenotypes similar to clinical
      NEPC. Whole transcriptome analyses further reveal that SRRM4 induces a
      pluripotency gene network consisting of the stem-cell differentiation gene, SOX2.
      While SRRM4 overexpression enhances SOX2 expression in both time- and dose
      dependent manners in DU145 cells, RNA depletion of SOX2 compromises SRRM4
      mediated stimulation of pluripotency genes. More importantly, this SRRM4-SOX2
      axis is present in a subset of NEPC patient cohorts, patient-derived xenografts,
      and clinically relevant transgenic mouse models. INTERPRETATION: We report a
      novel mechanism by which SRRM4 drives NEPC progression via a pluripotency gene
      network. FUND: Canadian Institutes of Health Research, National Nature Science
      Foundation of China, and China Scholar Council.

PMID- 30100396
TI  - Glucose and Insulin-Related Traits, Type 2 Diabetes and Risk of Schizophrenia: A
      Mendelian Randomization Study.
AB  - BACKGROUND: The link between schizophrenia and diabetes mellitus is well
      established by observational studies; however, the cause-effect relationship
      remains unclear. METHODS: Here, we conducted Mendelian randomization analyses to
      assess a causal relationship of the genetic variants related to elevated fasting
      glucose levels, hemoglobin A1c (HbA1c), fasting insulin levels, and type 2
      diabetes with the risk of schizophrenia. The analyses were performed using
      summary statistics obtained for the variants identified from the genome-wide
      association meta-analyses of fasting glucose levels (up to 133,010 individuals),
      HbA1c (up to 153,377 individuals), fasting insulin levels (up to 108,557
      individuals), type 2 diabetes (up to 659,316 individuals), and schizophrenia (up
      to 108,341 individuals). The association between each variant and schizophrenia
      was weighted by its association with each studied condition, and estimates were
      combined using an inverse-variance weighted meta-analysis. FINDINGS: Using
      information from thirteen variants related to fasting insulin levels, the causal
      effect of fasting insulin levels increases (per 1-SD) on the risk of
      schizophrenia was estimated at an odds ratio (OR) of 2.33 (p = 0.001), which is
      consistent with findings from the observational studies. The fasting glucose
      associated single nucleotide polymorphisms (SNPs) had no effect on the risk of
      schizophrenia in Europeans and East Asians (p > 0.05). Nonsignificant effects on
      the risk of schizophrenia was observed with raised HbA1c and type 2 diabetes, and
      consistent estimates were obtained across different populations. INTERPRETATION:
      Our results suggest a causal role of elevated fasting insulin levels in
      schizophrenia pathogenesis.

PMID- 30100397
TI  - Clinical prediction of HBV and HCV related hepatic fibrosis using machine
      learning.
AB  - Clinical prediction of advanced hepatic fibrosis (HF) and cirrhosis has long been
      challenging due to the gold standard, liver biopsy, being an invasive approach
      with certain limitations. Less invasive blood test tandem with a cutting-edge
      machine learning algorithm shows promising diagnostic potential. In this study,
      we constructed and compared machine learning methods with the FIB-4 score in a
      discovery dataset (n = 490) of hepatitis B virus (HBV) patients. Models were
      validated in an independent HBV dataset (n = 86). We further employed these
      models on two independent hepatitis C virus (HCV) datasets (n = 254 and 230) to
      examine their applicability. In the discovery data, gradient boosting (GB) stably
      outperformed other methods as well as FIB-4 scores (p < .001) in the prediction
      of advanced HF and cirrhosis. In the HBV validation dataset, for classification
      between early and advanced HF, the area under receiver operating characteristic
      curves (AUROC) of GB model was 0.918, while FIB-4 was 0.841; for classification
      between non-cirrhosis and cirrhosis, GB showed AUROC of 0.871, while FIB-4 was
      0.830. Additionally, GB-based prediction demonstrated good classification
      capacity on two HCV datasets while higher cutoffs for both GB and FIB-4 scores
      were required to achieve comparable specificity and sensitivity. Using the same
      parameters as FIB-4, the GB-based prediction system demonstrated steady
      improvements relative to FIB-4 in HBV and HCV cohorts with different cutoff
      values required in different etiological groups. A user-friendly web tool,
      LiveBoost, makes our prediction models freely accessible for further clinical
      studies and applications.

PMID- 30100399
TI  - Lactococcus lactis cholangitis and bacteremia identified by MALDI-TOF mass
      spectrometry: A case report and review of the literature on Lactococcus lactis
      infection.
AB  - Lactococcus lactis is a rare causative organism in humans. Cases of L. lactis
      infection have only rarely been reported. However, because it is often difficult
      to identify by conventional commercially available methods, its incidence may be
      underestimated. We herein report the case of a 70-year-old man with
      cholangiocarcinoma who developed L. lactis cholangitis and review previously
      reported cases of L. lactis infection. Our case was confirmed by matrix-assisted
      desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). This case
      shows L. lactis is a potential causative pathogen of cholangitis and that MALDI
      TOF MS can be useful for the rapid and accurate identification of L. lactis
      infection. We searched the literature for published case reports on cholangitis
      and any other infections caused by L. lactis, and thereby identified 36 cases,
      including our case. At least 66.7% (n = 24) of the cases had significant
      underlying conditions; 15 of the cases involved patients with an
      immunocompromised status. At least 41.7% (n = 15) had a significant food
      consumption history, such as the consumption of unpasteurized dairy products. The
      clinical sources of L. lactis were diverse and endocarditis was the most common
      diagnosis (n = 8), followed by hepatobiliary infection (n = 6), central nervous
      system infection (n = 5), and peritonitis (n = 4). The prognosis was favorable in
      most cases.

PMID- 30100398
TI  - Integrated analysis of DNA methylome and transcriptome identified CREB5 as a
      novel risk gene contributing to recurrent pregnancy loss.
AB  - BACKGROUND: Aberrant DNA methylation is considered to be a potential cause of
      recurrent pregnancy loss (RPL), while potential mechanism has not yet been
      elucidated. METHODS: In order to uncover the contribution of the perturbation of
      DNA methylation in RPL, we performed genome-wide DNA methylation analysis
      combined with genome-wide gene expression in decidua tissue. FINDINGS: Totally,
      539 differentially methylated regions (DMRs) were identified and significantly
      correlated with gene expressions. We observed that hypo-methylated DMR near CREB5
      recruited transcription factors binding, such as P53 and SP1, and in turn
      upregulated CREB5. Compromised cell migration and apoptosis were observed in
      human CREB5 overexpression trophoblast cell lines, indicating dysfunctional
      trophoblast cells might contribute to RPL after hypo-methylation of CREB5. In
      addition, overexpression of CREB5 altered cell cycle. INTERPRETATION: Our data
      highlights a role of CREB5 involved in the pathogenesis of RPL, and CREB5 maybe a
      potential diagnostic biomarker for RPL.

PMID- 30100400
TI  - Influenza vaccine showed a good preventive effect against influenza-associated
      hospitalization among elderly patients, during the 2016/17 season in Japan.
AB  - The 2016/17 influenza season in Japan was characterized by a predominance of
      influenza A (H3N2) activity; with H3N2 accounting for 85% of all detected
      influenza virus infections. We assessed the vaccine effectiveness (VE) of an
      inactivated quadrivalent influenza vaccine (IIV4) in adult patients, using a test
      negative case-control design study based on the results of a rapid influenza
      diagnostic test (RIDT). Between November 2016 and March 2017, a total of 1048
      adult patients were enrolled: including 363 RIDT positive for influenza A, 9 RIDT
      positive for influenza B, and 676 RIDT-negative. During the 2016/17 season, the
      overall adjusted VE was 28.8% (95% confidence interval [CI]: 6.3-46%). The
      adjusted VE against influenza A was 27.4% (95%CI: 4.4-45%). The VE against
      influenza B could not be estimated because of the very low number of influenza B
      patients. Twenty-nine patients were hospitalized due to influenza-associated
      illness-during the present study, all of whom were infected with influenza A
      virus. The adjusted VE, determined using a case-control study, for preventing
      hospitalization for influenza A infection was 72.6% (95%CI: 30.7-89.1%). In
      addition, the VE for preventing hospitalization of influenza patients with
      comorbidities was 78.2% (95%CI: 41.1-92%). Our study showed that, during the
      2016/17season, IIV4 was effective for preventing both the onset of influenza and
      influenza-associated hospitalization.

PMID- 30100401
TI  - Effect of sodium mercaptoacetic acid on different antimicrobial disks in the
      sodium mercaptoacetic acid double disk synergy test for detection of IMP-1
      metallo-beta-lactamase-producing Pseudomonas aeruginosa isolates in Japan.
AB  - We determined the optimal antimicrobial in the sodium mercaptoacetic acid double
      disk synergy test (SMA-DDST) for the detection of IMP-1-producing Pseudomonas
      aeruginosa isolates in Japan and evaluated the performance of the test. Fifty
      four P. aeruginosa clinical isolates were tested, including 39 IMP-1 producers
      and 15 non-metallo-beta-lactamase (MBL)-producing carbapenem- and ceftazidime
      (CAZ)-resistant isolates. The SMA-DDST was performed with CAZ, cefepime (CFPM),
      imipenem (IPM), meropenem (MEPM), doripenem (DRPM), or biapenem (BIPM)-containing
      disks. The sensitivity of the SMA-DDST with CAZ, CFPM, IPM, MEPM, DRPM, and BIPM
      was 39/39 (100%), 36/39 (92%), 18/39 (46%), 8/39 (21%), 19/39 (49%), and 36/39
      (92%), respectively. The specificity was 15/15 (100%) for all SMA-DDSTs. This
      suggests that the isolates may have a resistance mechanism other than MBL
      production for IPM, MEPM, or DRPM. Since the CAZ resistance mechanism in P.
      aeruginosa is the same as that of CFPM, but differs from that of carbapenems, we
      conclude that combining CAZ with BIPM SMA-DDSTs can prevent any failure in the
      detection of IMP-1-producing P. aeruginosa.

PMID- 30100402
TI  - cT1a renal masses < 2 versus > 2 cm managed with Robotic Partial Nephrectomy: a
      propensity-score matched comparison of perioperative Outcomes.
AB  - PURPOSE: To perform a single center evaluation comparing the perioperative,
      pathological and functional outcomes of robotic partial nephrectomy (RPN) for T1a
      renal masses < 2 cm vs T1a renal masses > 2 cm. MATERIALS AND METHODS: Propensity
      score 1:1 matching of queried patients was performed from the institutional RPN
      database (January 2007 - January 2017) by age, sex, race, BMI, Charlson's
      comorbidity Index, smoker status, diabetes, hypertension, hyperlipidemia, ASA
      score, eGFR, Chronic Kidney Disease stage and RENAL score. 524 patients were
      analyzed (262 < 2 cm vs 262 > 2 cm). Perioperative, pathological and functional
      outcomes were evaluated. RESULTS: Smaller renal masses (< 2 cm) had significantly
      lower operative time, blood loss, ischemia time (14.3 + 9.58 vs 21.5 + 9.51
      minutes, p < 0.001) and intraoperative transfusions (0 vs 2.7%, p = 0.015).
      Moreover, superior early renal functional outcome as assessed by eGFR at first
      postoperative day (83.1 + 21.3 vs 76.6 + 22.0, p = 0.001), higher percentage of
      parenchymal preservation (89.9 + 9.45 vs 83.6 + 8.20%, p < 0.001) and a trend
      towards a lower rate of postoperative complications (13.5 vs 19.5%, p = 0.080)
      were found. Higher percentage of malignancies was found in larger tumors (74.8 vs
      85.9%, p = 0.002), but no difference in positive surgical margins was recorded.
      CONCLUSIONS: RPN tends to be a low morbidity treatment modality for renal masses
      < 2 cm. Although active surveillance is a common option for such tumors, RPN
      remains an alternative for selected patients.

PMID- 30100405
TI  - That's a WRAP: laparoscopic anti-reflux surgery for idiopathic pulmonary
      fibrosis.

PMID- 30100404
TI  - Laparoscopic anti-reflux surgery for the treatment of idiopathic pulmonary
      fibrosis (WRAP-IPF): a multicentre, randomised, controlled phase 2 trial.
AB  - BACKGROUND: Abnormal acid gastro-oesophageal reflux (GER) is hypothesised to play
      a role in progression of idiopathic pulmonary fibrosis (IPF). We aimed to
      determine whether treatment of abnormal acid GER with laparoscopic anti-reflux
      surgery reduces the rate of disease progression. METHODS: The WRAP-IPF trial was
      a randomised controlled trial of laparoscopic anti-reflux surgery in patients
      with IPF and abnormal acid GER recruited from six academic centres in the USA. We
      enrolled patients with IPF, abnormal acid GER (DeMeester score of >=14.7;
      measured by 24-h pH monitoring) and preserved forced vital capacity (FVC). We
      excluded patients with a FVC below 50% predicted, a FEV1/FVC ratio of less than
      0.65, a history of acute respiratory illness in the past 12 weeks, a body-mass
      index greater than 35, and known severe pulmonary hypertension. Concomitant
      therapy with nintedanib and pirfenidone was allowed. The primary endpoint was
      change in FVC from randomisation to week 48, in the intention-to-treat population
      with mixed-effects models for repeated measures. This trial is registered with
      ClinicalTrials.gov, number NCT01982968. FINDINGS: Between June 1, 2014, and Sept
      30, 2016, we screened 72 patients and randomly assigned 58 patients to receive
      surgery (n=29) or no surgery (n=29). 27 patients in the surgery group and 20
      patients in the no surgery group had an FVC measurement at 48 weeks (p=0.041).
      Intention-to-treat analysis adjusted for baseline anti-fibrotic use demonstrated
      the adjusted rate of change in FVC over 48 weeks was -0.05 L (95% CI -0.15 to
      0.05) in the surgery group and -0.13 L (-0.23 to -0.02) in the non-surgery group
      (p=0.28). Acute exacerbation, respiratory-related hospitalisation, and death was
      less common in the surgery group without statistical significance. Dysphagia
      (eight [29%] of 28) and abdominal distention (four [14%] of 28) were the most
      common adverse events after surgery. There was one death in the surgery group and
      four deaths in the non-surgery group. INTERPRETATION: Laparoscopic anti-reflux
      surgery in patients with IPF and abnormal acid GER is safe and well tolerated. A
      larger, well powered, randomised controlled study of anti-reflux surgery is
      needed in this population. FUNDING: US National Institutes of Health National
      Heart, Lung and Blood Institute.

PMID- 30100403
TI  - Epigenetic prediction of response to anti-PD-1 treatment in non-small-cell lung
      cancer: a multicentre, retrospective analysis.
AB  - BACKGROUND: Anti-programmed death-1 (PD-1) treatment for advanced non-small-cell
      lung cancer (NSCLC) has improved the survival of patients. However, a substantial
      percentage of patients do not respond to this treatment. We examined the use of
      DNA methylation profiles to determine the efficacy of anti-PD-1 treatment in
      patients recruited with current stage IV NSCLC. METHODS: In this multicentre
      study, we recruited adult patients from 15 hospitals in France, Spain, and Italy
      who had histologically proven stage IV NSCLC and had been exposed to PD-1
      blockade during the course of the disease. The study structure comprised a
      discovery cohort to assess the correlation between epigenetic features and
      clinical benefit with PD-1 blockade and two validation cohorts to assess the
      validity of our assumptions. We first established an epigenomic profile based on
      a microarray DNA methylation signature (EPIMMUNE) in a discovery set of tumour
      samples from patients treated with nivolumab or pembrolizumab. The EPIMMUNE
      signature was validated in an independent set of patients. A derived DNA
      methylation marker was validated by a single-methylation assay in a validation
      cohort of patients. The main study outcomes were progression-free survival and
      overall survival. We used the Kaplan-Meier method to estimate progression-free
      and overall survival, and calculated the differences between the groups with the
      log-rank test. We constructed a multivariate Cox model to identify the variables
      independently associated with progression-free and overall survival. FINDINGS:
      Between June 23, 2014, and May 18, 2017, we obtained samples from 142 patients:
      34 in the discovery cohort, 47 in the EPIMMUNE validation cohort, and 61 in the
      derived methylation marker cohort (the T-cell differentiation factor forkhead box
      P1 [FOXP1]). The EPIMMUNE signature in patients with stage IV NSCLC treated with
      anti-PD-1 agents was associated with improved progression-free survival (hazard
      ratio [HR] 0.010, 95% CI 3.29 * 10-4-0.0282; p=0.0067) and overall survival
      (0.080, 0.017-0.373; p=0.0012). The EPIMMUNE-positive signature was not
      associated with PD-L1 expression, the presence of CD8+ cells, or mutational load.
      EPIMMUNE-negative tumours were enriched in tumour-associated macrophages and
      neutrophils, cancer-associated fibroblasts, and senescent endothelial cells. The
      EPIMMUNE-positive signature was associated with improved progression-free
      survival in the EPIMMUNE validation cohort (0.330, 0.149-0.727; p=0.0064). The
      unmethylated status of FOXP1 was associated with improved progression-free
      survival (0.415, 0.209-0.802; p=0.0063) and overall survival (0.409, 0.220-0.780;
      p=0.0094) in the FOXP1 validation cohort. The EPIMMUNE signature and unmethylated
      FOXP1 were not associated with clinical benefit in lung tumours that did not
      receive immunotherapy. INTERPRETATION: Our study shows that the epigenetic milieu
      of NSCLC tumours indicates which patients are most likely to benefit from
      nivolumab or pembrolizumab treatments. The methylation status of FOXP1 could be
      associated with validated predictive biomarkers such as PD-L1 staining and
      mutational load to better select patients who will experience clinical benefit
      with PD-1 blockade, and its predictive value should be evaluated in prospective
      studies. FUNDING: "Obra Social" La Caixa, Cellex Foundation, and the Health and
      Science Departments of the Generalitat de Catalunya.

PMID- 30100406
TI  - Inadequacy of pulse oximetry in the catheterization laboratory. An exploratory
      study monitoring respiratory status using arterial blood gases during cardiac
      catheterization with conscious sedation.
AB  - BACKGROUND: Benzodiazepines and opioids are commonly used for conscious sedation
      (CS) in cardiac catheterization laboratory (CCL) patients. Both drugs are known
      to predispose to hypoxemia, apnea and decreased responsiveness to PCO2, resulting
      in decreased arterial pH and PO2, as well as increased PCO2. We want to determine
      the effects of CS on arterial blood gas (ABG) in CCL patient, and identify if
      pulse oximetry monitoring is adequate. METHODS: We enrolled 18 subjects
      undergoing elective catheterization. Measurement of ABGs at one-minute intervals
      was done from the moment of arterial access until case end. The results of ABGs
      were not available to the clinician who administered sedation. Relationships of
      pH, PCO2, PaO2 and SaO2 were studied by plotting time series graphs. Significant
      changes were defined as pH <7.30, SaO2 < 90, and PCO2 > 50 mmHg. RESULTS: No
      significant change in pH, PCO2, PaO2 and SaO2 was noted in 4/18 (22%) subjects. A
      significant drop in SaO2 was noted in 4/18 (22%). A significant change in PCO2
      and/or pH was noted in 10/18 (55%) cases. Among the 16 (16/18) subjects receiving
      supplemental oxygen, 7 (7/18, 39%) had no drop in SaO2, but developed respiratory
      acidosis. At the end of the case, 5/18 (28%) subjects had respiratory acidosis
      with normal PaO2. CONCLUSION: Significant hypercarbia and acidosis occurred
      frequently in this small study during CS in patients undergoing cardiac
      catheterization. Relying on pulse oximetry alone especially with patients on
      supplemental oxygen may lead to failure in detecting respiratory acidosis in a
      significant number of patients.

PMID- 30100407
TI  - Use of the Ocelot catheter in iliac chronic total occlusion intervention.

PMID- 30100410
TI  - Untargeted voltammetric approaches for characterization of oxidation patterns in
      white wines.
AB  - Chemical and electrochemical changes associated with controlled oxidation were
      measured in thirteen commercial white wines, in order to evaluate the potential
      of linear sweep voltammetry to provide relevant information on the oxidative
      behavior of individual wines. For a given amount of oxygen consumed, substantial
      diversity of oxidative behaviors was observed. A good correlation (R2 = 0.69) was
      observed between the rate of O2 consumption of individual wines and the total
      charged passed during linear sweep voltammetry, but not with their Folin
      Ciocalteu values. Onset potential of anodic oxidation was also related to oxygen
      consumption capacity of wine, indicating an important contribution of easily
      oxidizable substrates. Subtraction of voltammograms of oxidized wines from their
      corresponding non-oxidized controls generated new voltammograms representative of
      the global changes induced by oxidation. These new voltammograms contained
      several features related to oxygen consumption rates of each wine, and could be
      considered as a 'wine oxidation signature'.

PMID- 30100408
TI  - iPSC-Derived Macrophages Effectively Treat Pulmonary Alveolar Proteinosis in
      Csf2rb-Deficient Mice.
AB  - Induced pluripotent stem cell (iPSC)-derived hematopoietic cells represent a
      highly attractive source for cell and gene therapy. Given the longevity,
      plasticity, and self-renewal potential of distinct macrophage subpopulations,
      iPSC-derived macrophages (iPSC-Mphi) appear of particular interest in this
      context. We here evaluated the airway residence, plasticity, and therapeutic
      efficacy of iPSC-Mphi in a murine model of hereditary pulmonary alveolar
      proteinosis (herPAP). We demonstrate that single pulmonary macrophage
      transplantation (PMT) of 2.5-4 * 106 iPSC-Mphi yields efficient airway residence
      with conversion of iPSC-Mphi to an alveolar macrophage (AMphi) phenotype
      characterized by a distinct surface marker and gene expression profile within 2
      months. Moreover, PMT significantly improves alveolar protein deposition and
      other critical herPAP disease parameters. Thus, our data indicate iPSC-Mphi as a
      source of functional macrophages displaying substantial plasticity and
      therapeutic potential that upon pulmonary transplantation will integrate into the
      lung microenvironment, adopt an AMphi phenotype and gene expression pattern, and
      profoundly ameliorate pulmonary disease phenotypes.

PMID- 30100409
TI  - Characterization and Transplantation of CD73-Positive Photoreceptors Isolated
      from Human iPSC-Derived Retinal Organoids.
AB  - Photoreceptor degenerative diseases are a major cause of blindness for which cell
      replacement is one of the most encouraging strategies. For stem cell-based
      therapy using human induced pluripotent stem cells (hiPSCs), it is crucial to
      obtain a homogenous photoreceptor cell population. We confirmed that the cell
      surface antigen CD73 is exclusively expressed in hiPSC-derived photoreceptors by
      generating a fluorescent cone rod homeobox (Crx) reporter hiPSC line using
      CRISPR/Cas9 genome editing. We demonstrated that CD73 targeting by magnetic
      activated cell sorting (MACS) is an effective strategy to separate a safe
      population of transplantable photoreceptors. CD73+ photoreceptor precursors can
      be isolated in large numbers and transplanted into rat eyes, showing capacity to
      survive and mature in close proximity to host inner retina of a model of
      photoreceptor degeneration. These data demonstrate that CD73+ photoreceptor
      precursors hold great promise for a future safe clinical translation.

PMID- 30100411
TI  - Aging of Malbec wines from Mendoza and California: Evolution of phenolic and
      elemental composition.
AB  - This work aimed to investigate the evolution of phenolic compounds and elements
      during the aging of Malbec red wines from different regions of Mendoza
      (Argentina) and California (United States). The profiles of low molecular weight
      polyphenols and anthocyanins were analyzed using high-performance liquid
      chromatography with a diode-array detector (HPLC-DAD), and the elemental
      composition using microwave plasma-Atomic emission spectrometry (MP-AES). Through
      uni- and multivariate statistical analyses, the effects of aging time and region
      on wine were investigated. It was observed that aging time was a significant
      factor that affected the phenolic compound profile in the studied Malbec wines
      studied and that after five years of aging, the wines could be differentiated
      according to region. The results of this study may impact decisions made
      regarding the storage of Malbec wines in the future.

PMID- 30100412
TI  - Extraction, isolation of heat-resistance phenolic compounds, antioxidant
      properties, characterization and purification of 5-hydroxymaltol from Turkish
      apple pulps.
AB  - Apple pulps (AP) were obtained as a side product in fruit juice factories and
      contains valuable phenolic compounds. The dried AP was subjected to extraction
      with water, ethyl acetate (APEA) and n-butanol (APBU), respectively. 5
      Hydroxymaltol (5-HM) was isolated and confirmed by NMR techniques. The HPLC
      TOF/MS analysis revealed the presence of 16 components including major components
      of morine, gentisic, 4-hydroxybenzoic, vanillic and fumaric acid. The antioxidant
      activities were evaluated with total antioxidant activity, reducing power,
      inhibition of lipid peroxidation, metal chelating, free radical and H2O2
      scavenging activities. 5-HM, APEA and APBU exhibited the in vitro antioxidant
      activities in a concentration-dependent and moderate manner. The IC50 values were
      effective for free radical scavenging activity of 5-HM (8.22 MUg mL-1), H2O2
      scavenging activity for APEA (8.12 MUg mL-1) and inhibition of lipid peroxidation
      for APEA (0.93 MUg mL-1). The 5-HM and APEA have antioxidant capacities and also
      feasible to apply variety in vivo tests.

PMID- 30100413
TI  - Effect of extrusion on folic acid concentration and mineral element dialyzability
      in Great Northern beans (Phaseolus vulgaris L.).
AB  - Great Northern beans (GNB) contain appreciable magnesium (Mg), potassium (K),
      phosphorus (P), and iron (Fe), together with the heat-labile vitamin, folate, and
      the anti-nutritional compound phytate. Thus, the objective was to increase
      dialyzability of essential mineral elements while degrading phytate and
      minimizing destruction of folate through extrusion of GNB. Extrusion resulted in
      significant (p < 0.05) increases in dialyzability of Mg, P, K, and Fe by as much
      as 50%, 30%, 5%, and 79%, respectively, while decreasing cadmium (Cd)
      dialyzability. Screw speed (SS) had a significant quadratic effect on
      dialyzability of all elements. Low MC resulted in a significant reduction (46%)
      in phytate, although this was accompanied by as much as 24% destruction of
      folate. In conclusion, low barrel temperature, medium MC and high SS were
      identified as the optimum conditions to maximize essential mineral element
      dialyzability and folate retention while minimizing phytate and dialyzable Cd.

PMID- 30100414
TI  - Multi-class polar lipid profiling in fresh and roasted hazelnut (Corylus avellana
      cultivar "Tonda di Giffoni") by LC-ESI/LTQOrbitrap/MS/MSn.
AB  - Hazelnuts are a popular tree nut used whole or as an ingredient in a variety of
      bakery, candy and chocolate products. Based on the nutritional value and
      nutraceutical properties, mainly due to the lipid content, US Food and Drug
      Administration has recognized hazelnut as "heart-healthy" food. "Nocciola di
      Giffoni" is a Protected Geographical Indication (PGI) Italian hazelnut largely
      consumed but lacking of a comprehensive lipid profile. To acquire a detailed
      characterization of the polar lipids in fresh and roasted "Nocciola di Giffoni"
      hazelnut, an extensive analysis based on high-performance liquid chromatography
      coupled to multiple-stage linear ion-trap and orbitrap high-resolution mass
      spectrometry (LC-ESI/LTQOrbitrap/MS/MSn) was carried out. This analytical
      approach (statistically validated) allowed for the detection of a wide range of
      polar lipids from oxylipins and long chain bases to high molecular weight lipids
      (phospholipids, sphingolipids, and glycolipids). Most of the polar lipids are
      here described for the first time in hazelnut.

PMID- 30100415
TI  - Dissipation and safety evaluation of novaluron, pyriproxyfen, thiacloprid and
      tolfenpyrad residues in the citrus-field ecosystem.
AB  - The dissipations and residues of four pesticides in citrus, under field
      conditions, were measured using solid-phase extraction and LC-MS/MS. In the
      method validation, satisfactory results were obtained with fortified recoveries
      ranging from 80.6 to 113% and relative standard deviations <=9.0%. In the
      dissipation test, the half-lives for the pesticides in citrus, according to first
      order kinetics, ranged from 13.3 to 28.9 days. Based on the terminal residue
      test, two evaluation models (hazard quotient, HQ; risk quotient, RQ) were applied
      on citrus fruits for dietary exposure risk assessment. The results showed that
      HQs ranged from 0.0031 to 0.78%, and RQs from 7.3 to 57%, which are both
      acceptable for human consumption. Therefore, 14-day was proposed as a pre-harvest
      interval for the target compounds in citrus fruits. This work also contributes to
      residue data and, therefore, scientifically validated maximum residue limits in
      citrus, which are lacking in China currently.

PMID- 30100416
TI  - Butylated hydroxyanisole encapsulated in gelatin fiber mats: Volatile release
      kinetics, functional effectiveness and application to strawberry preservation.
AB  - Butylated hydroxyanisole (BHA) encapsulated in gelatin (GA) (GA-BHA) fiber mats
      were fabricated via electrospinning technique and applied to strawberry
      preservation. The volatile release kinetics and functional effectiveness of the
      mats were investigated. BHA was high efficiently encapsulated in GA fibers and
      the antioxidant activity of BHA could be well protected. The encapsulation of BHA
      enhanced the stability of GA and favored structure transition of GA from random
      coil and beta-turns to alpha-helix and beta-sheet. The GA-BHA mats showed good
      antibacterial activity against Staphylococcus aureus, and the predominant
      volatile release mechanism of BHA from mats was Fickian diffusion. Furthermore,
      the mats also showed broad-spectrum antifungal activity against four mould genera
      (Rhizopus sp., Mucor sp., Aspergillus sp. and Penicillium sp.). The shelf-life of
      strawberry can be prolonged effectively in the presence of GA-BHA mats during
      storage. Results suggested that the GA-BHA mats may have a great potential in
      active food packaging.

PMID- 30100417
TI  - Rapid qualitative and quantitative analyses of eighteen phenolic compounds from
      Lycium ruthenicum Murray by UPLC-Q-Orbitrap MS and their antioxidant activity.
AB  - Lycium ruthenicum Murray (LR) is a functional food, and it has long been used in
      traditional folk medicine. However, detailed qualitative and quantitative
      analyses related to its phenolic compounds remains scarce. This work reports, for
      the first time, the establishment of a rapid method for simultaneous
      identification and quantification of 25 phenolic compounds by UPLC-quadrupole
      Orbitrap mass spectrometry (UPLC-Q-Orbitrap MS). This method was validated by
      LODs, LOQs, precision, repeatability, stability, mean recovery, recovery range
      and RSD. The confirmed method was applied to the analysis of phenolic compounds
      in LR. Finally, 18 phenolic compounds in LR were qualitatively and quantitatively
      analyzed. Among them, 11 constituents were detected for the first time, which
      included two flavonoids (catechin and naringenin) and seven phenolic acids
      (gallic acid, vanillic acid, 2,4-dihydroxybenzoic acid, veratronic acid, benzoic
      acid, ellagic acid and salicylic acid). Moreover, Phloretin and protocatechuate,
      belonging to the dihydrochalcone flavonoid and protocatechuic acid respectively,
      were also identified and quantified. The total phenolics content (20.17 +/- 2.82
      mg/g) and the total anthocyanin content (147.43 +/- 1.81 mg/g) were determined.
      In addition, the antioxidant activities of the LR extract were evaluated through
      2,2-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical scavenging
      activity, ferric reducing antioxidant power (FRAP) and total antioxidant activity
      (T-AOC) assays.

PMID- 30100418
TI  - Integrated analyses of phenolic compounds and minerals of Brazilian organic and
      conventional grape juices and wines: Validation of a method for determination of
      Cu, Fe and Mn.
AB  - The phenolic profile and antioxidant activity (AOX) of "organic vs. conventional"
      Brazilian wines and grape juices were analyzed. A simple method for the
      determination of minerals Cu, Fe and Mn by F-AAS was validated and used to
      characterize the samples studied. In the validation of the Cu, Fe and Mn
      determination method, the protocol for samples preparation by hot digestion with
      HNO3 + H2O2 proved to be more suitable for the grape juice and wine matrices. The
      validation parameters were considered satisfactory. Conventional products
      presented higher anthocyanins content, and no significant differences were
      observed on other phenolic compounds, AOX and Cu, Fe and Mn minerals. All the
      evaluated samples presented similar results between the same cultivars and in
      products from grapes of the two cultivation systems. The AOX of juices and wines,
      organic and conventional, was high, and correlated with procyanidin B1, petunidin
      3-glucoside and cyanidin-3,5-diglucoside.

PMID- 30100419
TI  - An electrooxidative technique to fast fabricate copper phosphate electrodes
      capable of integrating high performance liquid chromatography for the label-free
      detection of fish freshness.
AB  - A simple and fast one-step electrooxidative method has been developed to
      monolithically produce a copper phosphate (Cu3(PO4)2) compound on a disposable
      copper tape, which can be integrated with high performance liquid chromatography
      (HPLC) for the estimation of fish freshness. The Cu3(PO4)2 compound of flake-like
      nanostructures was formed by applying a first anodic peak potential at the copper
      tape for 10 min in a 1 M sodium dihydrogen phosphate (NaH2PO4) (pH 5.0) solution.
      The Cu3(PO4)2 electrodes can detect the oxidative reaction of histidine and
      histamine in 20 mM NaH2PO4 solutions with pH 5.0-8.5. When integrating the
      electrodes with a flow injection system, the linear range and the calculated
      detection limit of histamine were respectively 2.5-250 ppm and 0.15 ppm. The
      electrodes integrated to HPLC can specifically detect the histamine
      concentrations in fish samples in the pH 7.5 NaH2PO4 solution, achieving an
      accuracy rate of 95.3% and a recovery rate of 101.1%.

PMID- 30100420
TI  - Rapid analysis of paralytic shellfish toxins and tetrodotoxins by liquid
      chromatography-tandem mass spectrometry using a porous graphitic carbon column.
AB  - Although paralytic shellfish toxins (PSTs) have traditionally been analyzed by
      liquid chromatography with either pre- or post-column derivatization, and these
      methods have been validated successfully through inter-laboratory studies, mass
      spectrometry methods have also been described in literature for use in monitoring
      programs. However, methods using liquid chromatography coupled with mass
      spectrometry (LC-MS) need to be improved in terms of sensitivity, analyte
      recovery and retention time stability because of undesirable matrix effects.
      Furthermore, tetrodotoxin (TTX) has been found in northern European bivalves, so
      it is important to analyze TTX compounds alongside PSTs because characteristics
      of their toxicity are similar. This paper describes, for the first time, a
      chemical method that allows determination of PSTs, both hydrophilic and
      hydrophobic, alongside TTX and its analogue 4,9-anhydro tetrodotoxin (4,9-anhTTX)
      with LC-MS/MS using a Hypercarb(r) column. The method was validated for 13
      hydrophilic PSTs and TTXs and was able to discriminate six hydrophobic PSTs in 20
      min. The method was developed for four shellfish matrices: mussel (Mytillus
      galloprovincialis), clam (Ruditapes decussatus), scallop (Pecten maximus) and
      oyster (Ostrae edulis). Clean-up procedure used in this work allowed us to obtain
      good results for validation parameters for both PSTs and TTXs. No standards were
      available so strains of Gymnodinium catenatum (G. catenatum) were used instead.

PMID- 30100421
TI  - Comparative study of raw and germinated Chenopodium (Chenopodium album) flour on
      the basis of thermal, rheological, minerals, fatty acid profile and
      phytocomponents.
AB  - This study determined the effects of germination on the minerals, fatty acids,
      pasting, thermal, rheological and phytocomponents contents of Chenopodium album
      flour. The predominant fatty acids in raw flour were palmitic (0.83%), oleic
      (0.99%) and linoleic acids (1.96%), which increased significantly (p <= 0.05)
      with germination. Minerals (Na, Cu and Zn) and dietary fiber (soluble and
      insoluble) were increased with germination, while pasting and gelatinization
      properties were reduced significantly. Scanning electron micrographs showed
      destruction of the continuous composite structure of starch embedded in the dense
      protein matrix of flour following germination. Quantitative analysis of C. album
      flour by GC-MS revealed that germinated flour contained more phytocompounds than
      raw flour. This research suggests the potential of germination in enhanced
      product development and utilization of valuable bioactive compounds.

PMID- 30100422
TI  - One-pot preparation of an acryloyled beta-cyclodextrin-silica hybrid monolithic
      column and its application for determination of carbendazim and carbaryl.
AB  - This work describes, for the first time, an acryloyled beta-cyclodextrin hybrid
      monolith column was synthesized, under aqueous-phase conditions, and used for
      solid-phase microextraction of carbendazim and carbaryl. The monolithic column
      was characterized using scanning electron microscopy, nitrogen adsorption
      desorption, thermogravimetric analysis and Fourier transform infrared
      spectroscopy, and used as the adsorbent for solid phase microextraction (SPME) of
      carbendazim and carbaryl. After optimization of the SPME conditions, a simple and
      sensitive SPME-HPLC method was developed for the determination of carbendazim and
      carbaryl in leafy vegetables. The method exhibited a good liner response in the
      range 5-400 MUg/kg (R2 = 0.9994) for carbendazim and 10-400 MUg/kg (R2 = 0.9996)
      for carbaryl, respectively. The limits of detection were 1.0 and 1.5 MUg/kg for
      carbendazim and carbaryl, respectively, in leafy vegetables. Recoveries ranged
      from 92.6% to 110.1%, and the relative standard deviations were less than 6.1%.

PMID- 30100423
TI  - Simultaneous determination of seven preservatives in food by dispersive liquid
      liquid microextraction coupled with gas chromatography-mass spectrometry.
AB  - A simple, rapid, inexpensive and environment-friendly method, based on dispersive
      liquid-liquid microextraction (DLLME) coupled with gas chromatography-mass
      spectrometry (GC-MS), was developed for the determination of food preservatives
      including benzoic acid (BA), sorbic acid (SA), dehydroacetic acid and four
      parabens. Optimum DLLME conditions were determined as follows: extraction solvent
      (chloroform) volume, 50 MUL; disperser solvent (acetone) volume, 0.5 mL; NaCl
      amount, 0.50 g/4 mL sample solution at pH 4.0. Hydroquinone was selected as the
      internal standard. The calibration curves were linear in the range 0.05-10 mg L-1
      for BA, SA and methylparaben, and 0.02-10 mg L-1, for the remainder. Limits of
      detection were in the range 0.15-0.50 mg kg-1 with enrichment factors ranging
      from 25 to 114 for all target analytes. Recoveries were in the range 88.7-110.5%
      with a relative standard deviation of less than 5%.

PMID- 30100424
TI  - Performance and mechanism of an innovative humidity-controlled hot-air drying
      method for concentrated starch gels: A case of sweet potato starch noodles.
AB  - The effects of humidity control on dried starch gels were investigated using
      starch noodles as a model. A two-stage innovative hot-air-drying regime was
      developed with the first stage humidity-controlled (70  degrees C, 60% RH) and
      the second at high temperature (100  degrees C). The proposed drying method is
      comparable to natural-air-drying in product quality and to conventional hot-air
      drying (70  degrees C) in production efficiency. The operating humidity of the
      first stage predominated the swelling index and rehydration ratio of dry noodles
      as well as the hardness and chewiness of cooked noodles. The results from XRD,
      DSC, SEM, digital microscopy and low field TD 1H NMR evidenced that these
      outcomes were largely ascribed to the higher shrinkage, lower porosity, smoother
      surface, lesser shape deformation and higher starch retrogradation resulting from
      increased humidity. The results reported herein are valuable for regulating the
      physicochemical properties of dried starch gels and glimpsing the underlying
      mechanisms of related operations.

PMID- 30100425
TI  - Formation mechanism of the oolong tea characteristic aroma during bruising and
      withering treatment.
AB  - To elucidate formation mechanism of oolong tea aroma, the released and remaining
      volatiles during bruising and withering treatment were analyzed using head space
      solid-phase microextraction/gas chromatography-mass spectrometry. An increase in
      proportion of the released terpenoid volatiles (TVs) along with a decrease in
      proportion of the released C6 green leaf volatiles (GLVs) was observed in both
      cultivars 'Zhejiang139' and 'Foshou'. Proportion of remaining TVs also fluctuated
      reversely with GLVs although the level of these volatiles increased remarkably.
      High ratio of TVs to GLVs was the key chemical foundation of oolong tea
      characteristic aroma and could be regarded as a good indicator in screening
      cultivar for suitably producing high quality oolong tea. Combining with
      transcriptome analysis, increased TVs and GLVs during the treatment might be
      largely generated through de novo synthesis and modulated at transcript level
      through up-regulation of genes involved in terpenoids metabolism and enzymatic
      cleavage of long-chain fatty acids.

PMID- 30100426
TI  - The effect of organic salts on the browning of dried squid products processed by
      air-drying.
AB  - To control discoloration of dried Japanese common squid (Todarodes pacificus)
      product, influence of 0-1% organic salts, including sodium gluconate (Na
      gluconate), sodium citrate (Na-citrate), sodium phytate (Na-phytate), sodium
      benzoate (Na-benzoate) and sodium tartrate (Na-tartrate), on Maillard browning in
      the squid meat during air-drying was investigated. Changes in surface color of
      the dried squid were mitigated by the addition of organic salts. Organic salts
      also showed inhibitory effects on autolysis and generation of free amino acids
      (FAAs), especially arginine, in both the dried squid meat and the model solution.
      Moreover, Maillard reaction degree of the dried squid was decreased by using
      organic salts. The addition of 1% Na-citrate or 1% Na-phytate well suppressed the
      browning of the dried squid (p < 0.05). The results indicated that organic salts
      having strong chelating ability, including Na-citrate and Na-phytate, can prevent
      the browning of the dried squid product by inhibiting the generation of FAAs.

PMID- 30100427
TI  - Comparative proteomics analysis reveals the effect of germination and selenium
      enrichment on the quality of brown rice during storage.
AB  - Selenium (Se) can delay the quality deterioration of rice during storage,
      however, the mechanisms remain unclear. In this study, changes in the quality of
      brown rice, germinated brown rice, and selenized germinated brown rice stored at
      38  degrees C and 90% relative humidity with various vacuum levels for 120 or 150
      days were investigated. Fatty acid value and carbonyl value were determined every
      30 days. Comparative proteomics technology was applied to determine the
      mechanisms of germination and Se enrichment on the storage quality of rice.
      Approximately 142 abundance changed proteins were found, of which 37 proteins
      were identified. By functional classification, proteins involved in processes of
      carbohydrate metabolism, lipid metabolism, oxidation-reduction, and protein
      catabolism may contribute to the different storage qualities of three samples.
      This study provides novel insights into Se response in rice at the proteome
      level, which are expected to be beneficial for exploring Se response tracts in
      rice.

PMID- 30100428
TI  - Quantitative differences in whey proteins among Murrah, Nili-Ravi and
      Mediterranean buffaloes using a TMT proteomic approach.
AB  - The aim of this study was to characterize whey proteins and their potential
      activities among buffalo breeds. In this work, a tandem mass tag (TMT) proteomic
      approach was used to identify the differences in the proteomes of milk whey
      proteins in Murrah, Nili-Ravi and Mediterranean buffaloes. A total of 580
      proteins were identified in buffalo milk whey, and the subunits of the 62
      differentially expressed proteins are shown in clustering analysis. Whey proteins
      with relatively higher levels in Mediterranean buffalo milk than in Murrah and
      Nili-Ravi buffalo milk included polymeric immunoglobulin receptor, alpha1
      antiproteinase, heat shock cognate 71-kDa protein, and Acyl-CoA-binding protein.
      Most of the differentially expressed proteins participate in complement and
      coagulation cascades, which are strongly related to immune protective activities.
      These results provide insight into the complexity of the buffalo milk whey
      proteome and provide molecular evidence for nutritive differences among buffalo
      breeds.

PMID- 30100429
TI  - Combined effect of CaCl2 and high pressure processing on the solubility of
      chicken breast myofibrillar proteins under sodium-reduced conditions.
AB  - The combined effect of calcium chloride (CaCl2) (20-100 mM) and high pressure
      processing (HPP, 200 MPa) on the solubility of myofibrillar proteins (MP) was
      investigated under sodium-reduced conditions (0.3 M sodium chloride). The results
      revealed that HPP combined with low concentrations (<40 mM) of CaCl2
      synergistically increased the solubility of MP, but an antagonistic effect
      occurred when a high concentration (100 mM) of CaCl2 was present. This
      synergistic effect could be attributed to a mildly destabilized conformation of
      myosin, an increased surface hydrophobicity and the decreased total sulfhydryl
      group content of MP. However, CaCl2 at 100 mM destabilized myosin to a larger
      extent and induced non-disulfide covalent cross-linking of S-1 subfragment in
      pressurized MP, thus attenuating the solubilizing effect of HPP on the myosin
      heavy chain, resulting in the antagonistic effect. Therefore, HPP in combination
      with low-level CaCl2 (<40 mM) may improve the functional properties of sodium
      reduced meat products.

PMID- 30100430
TI  - Effects of brewing conditions on the phytochemical composition, sensory qualities
      and antioxidant activity of green tea infusion: A study using response surface
      methodology.
AB  - Green tea is a highly consumed beverage, and the phytochemical composition,
      sensory qualities, and antioxidant activity of tea infusion are significantly
      affected by brewing conditions. However, the simultaneous effects of brewing
      conditions on the infusion are unknown. This study aimed to model the effects of
      brewing conditions (temperature, time, water/tea ratio and particle size) on the
      phytochemical composition, sensory profiles and antioxidant activity of green tea
      infusion using response surface methodology. The regression models describing the
      brewing of detected indexes were significant (p <= 0.01) and reliable (R2 >=
      0.854). Particle size had the greatest negative effects on the phytochemical
      composition and antioxidant activities of tea infusion. Optimization of brewing
      conditions performed for five types of needs and preferences for consuming were
      verified to be credible. In particular, optimal conditions of overall acceptance
      were 82  degrees C (temperature), 5.7 min (time), 70 mL/g (water/tea ratio), and
      1100 um (particle size).

PMID- 30100431
TI  - Insights into the crystallinity and in vitro digestibility of chestnut starch
      during thermal processing.
AB  - The crystallinity is of importance for in vitro digestibility of starch. Six
      chestnut cultivars were selected to study the relationship between the
      crystallinity and in vitro digestibility of chestnut starch during thermal
      processing. After heat treatment, the total starch and amylose content remained
      unchanged or decreased, but the amount of damaged starch increased significantly
      (P < 0.05). Thermal processing enhanced the short-range ordered structure of
      starch and reduced its relative crystallinity. Thermal processing also decreased
      the resistant starch (RS) content, but a high RS content (57.2-67.9% of total
      starch) still remained in cooked chestnut starch. The relative crystallinity was
      negatively correlated with the estimated glycemic index (eGI) (r = -0.6416), and
      positively correlated with RS content (r = 0.6189). Accordingly, by altering the
      relative crystallinity and damage degree of chestnut starch, thermal processing
      changed the overall starch fractions and eGI, which can affect the overall in
      vitro digestibility.

PMID- 30100432
TI  - Determination of acetate and formate in vegetable oils by ion chromatography
      after multivariate optimization of the extraction process using a Doehlert
      design.
AB  - In this work, we present the development of a method for the determination of
      acetate and formate in vegetable oils by ion chromatography with conductometric
      detection following their extraction from samples using a diluted KOH solution.
      The extraction procedure was optimized using a multivariate approach. The
      application of a 24 full factorial design showed that the mass of sample,
      extraction time, and KOH concentration presented significant influence on the
      extraction of both acetate and formate, whereas the temperature presented little
      influence on the process. As a result, we set the extraction temperature at 22 
      degrees C and performed the multivariate optimization of the other variables
      using a Doehlert design. The optimum conditions were: 4.8 g of sample, 8 mmol L-1
      KOH solution and 19 min extraction time. Six samples of vegetable oils (soybean,
      corn, canola, sunflower and olive) were analyzed and recovery tests provided
      recovery percentages in the range of 82-118%.

PMID- 30100433
TI  - Establishment of ultrasound-assisted extraction of phenolic compounds from
      industrial potato by-products using response surface methodology.
AB  - Potato processing generates large amounts of by-products, which include potato
      peels and the outer layers of flesh, which contain phenolic compounds. The
      purpose of this study was to establish an extraction method for phenolic
      compounds from industrial potato by-products by using response surface
      methodology (RSM). Box-Behnken design (BBD) was performed to optimize the
      extraction conditions of phenolic compounds considering different extraction
      temperature, ratios of ethanol/water, time of extraction and sample/solvent
      ratio. The optimum extraction conditions were obtained with ethanol/water 55/45
      (v/v) by ultrasound bath during 35 min at 35  degrees C and 1/10 sample/solvent
      ratio. The best conditions were applied to determine the phenolic content in five
      potato by-products. The analyses by HPLC-DAD-ESI-MS showed that chlorogenic acid
      accounted for a 49.3-61% of the total phenolic compounds. Positive Pearson
      correlations between HPLC data and antioxidant activity confirmed that the
      phenolic compounds had significant antioxidant properties.

PMID- 30100434
TI  - Seaweeds from the Portuguese coast as a source of proteinaceous material: Total
      and free amino acid composition profile.
AB  - The total protein content and the (total and free) amino acid composition of nine
      edible species of red, brown and green seaweeds collected in the Portuguese North
      Central coast were quantified to assess their potential contribution to the
      recommended dietary intake. Whenever possible, the protein and amino acid
      composition was compared with that of commercial European seaweeds. The protein
      content was the highest (P < 0.05) in red species (19.1-28.2 g/100 g dw),
      followed by the green seaweed Ulva spp. (20.5-23.3 g/100 g dw), with the lowest
      content found in brown seaweeds (6.90-19.5 g/100 g dw). Brown seaweeds presented
      the lowest mean contents of essential amino acids (EAAs) (41.0% protein) but
      significantly (P < 0.05) higher concentrations of non-essential amino acids
      (36.1% protein) and free amino acids (6.47-24.0% protein). Tryptophan, methionine
      and leucine were the limiting EAAs in all species. In contrast, lysine was found
      in high concentrations, especially in red (2.71-3.85% protein) and green (2.84
      4.24% protein) seaweeds.

PMID- 30100435
TI  - UHPLC-HRMS-based tissue untargeted metabolomics study of naringin and hesperidin
      after dietary supplementation in chickens.
AB  - To date numerous metabolomic studies have been performed in order to characterize
      nutritional intervention studies. The aim of the current study was to present a
      comprehensive pipeline for characterizing the metabolic changes that occur in
      chickens tissues in response to naringin and hesperidin dietary supplementation.
      Forty-nine chickens were randomly divided into 3 groups: the first one fed with
      diet supplemented with naringin, the second with hesperidin whereas the control
      group was fed by commercial basal diet. After 30 days of administration chicken
      muscle samples were analyzed by UHPLC-HRMS whereas data were analyzed by the
      proposed pipeline. Three significant variables were detected to discriminate the
      control from the group after naringin administration and thirteen variables after
      hesperidin supplementation. Furthermore, a more detailed pipeline (encompassing
      multiple internal standards, internal validation of the clustering, extended
      statistical significance scores and multiple identification procedures) has been
      proposed aiming towards a more accurate untargeted analysis.

PMID- 30100436
TI  - Essential oils encapsulated in polymer-based nanocapsules as potential candidates
      for application in food preservation.
AB  - The aim of this work is the encapsulation of essential oils (EOs) in polymeric
      nanocapsules (NCs), in order to enhance their antimicrobial activity against food
      borne pathogens. Thymus capitatus and Origanum vulgare EOs were selected for
      their different chemical composition, carvacrol (73%) and thymol (44%) being the
      major constituent, respectively. Polymeric poly(E-caprolactone) (PCL)
      nanocapsules loaded with EOs were prepared by a nanoprecipitation method. The EO
      NCs showed monomodal distribution with diameter size 171 and 175 nm, high
      efficiency of encapsulation and stability with high retention of EOs at both 4 
      degrees C and 40  degrees C, for a period of at least 30 days. The antimicrobial
      activity of EO-NCs against food-borne pathogens was higher than that of the
      corresponding pure essential oils and the NCs loaded with Thymus capitatus EO
      were the most active. Interestingly EO-NCs showed a bactericidal activity even at
      the minimum inhibitory concentrations (MICs). It makes them appealing as natural
      food preservatives.

PMID- 30100437
TI  - Effects of microencapsulation by ionic gelation on the oxidative stability of
      flaxseed oil.
AB  - Flaxseed oil is a major source of omega-3 polyunsaturated fatty acids (PUFAs), as
      it contains nearly 50% of alpha-linolenic acid. For this reason it is highly
      susceptible to auto-oxidation. The aim of the work was to increase the stability
      of flaxseed oil by a microencapsulation process based on ionic gelation through
      vibrating-nozzle extrusion technology, using pectin as shell material. Two
      different drying systems, passive air drying (AD) and fluid bed (FB), were
      compared. The results show that the encapsulation efficiency is very high (up to
      98%). Besides being approximately 20-fold faster, FB gives beads showing on
      average higher payload (76% vs 68%) and lower peroxide value (9.64 vs 21.33) than
      the AD. An accelerated test carried out on FB-dried beads shows that the
      oxidative stability of encapsulated oil is 13-fold higher than bulk oil (PV FB:
      20 vs PV oil: 260), demonstrating the protecting effect of microencapsulation.

PMID- 30100438
TI  - Microwave pretreatment and optimization of osmotic dehydration of wild
      blueberries using response surface methodology.
AB  - This study investigated the effects of pretreatments and optimized osmotic
      dehydration (OD) of lowbush blueberries using response surface methodology (RSM)
      to produce dehydrated blueberries with high antioxidants content and shelf life.
      Fresh wild blueberries (WB) were initially pretreated and then subjected to
      osmotic dehydration. Microwave pretreated WB had shown better water loss during
      osmotic dehydration as compared to other pretreatment methods investigated. The
      highest levels of phenolics, flavonoids, and anthocyanin content of the
      dehydrated WB were found to be 742.61 mg/100 g, 263.12 mg/100 g, and 428.11
      mg/100 g d.m respectively, at optimized temperature of 40  degrees C, for 5 h OD,
      with 65% (w/w) Brix and 1:5 ratio of sample to Brix%. These results revealed that
      with rigorous optimization of the critical osmotic dehydration parameters high
      level of antioxidants could be obtained in the dehydrated product.

PMID- 30100440
TI  - Cocoa and chocolate are sources of vitamin D2.
AB  - Cocoa beans are susceptible to fungal contamination and often contain substantial
      amounts of ergosterol, the precursor to vitamin D2. We hypothesized that sun
      drying the fermented cocoa beans might lead to the conversion of ergosterol to
      vitamin D2. We quantified vitamin D in cocoa and cocoa-based foods by liquid
      chromatography-tandem mass spectrometry. Here, we show that cocoa beans from
      different growing regions contain vitamin D2. Particularly high vitamin D2
      content was found in cocoa powder and butter. Among the chocolates, dark
      chocolate had the highest vitamin D2 content (ranging from 1.90 to 5.48 ug/100
      g), white chocolate had the lowest vitamin D2 content (ranging from 0.19 to 1.91
      ug/100 g), and chocolate nut spreads had a comparatively low vitamin D2 content,
      with an average of 0.15 ug/100 g. Thus, cocoa and chocolate are clearly a dietary
      source of vitamin D, therefore, it is necessary to update food composition
      databases.

PMID- 30100439
TI  - High hydrostatic pressure reducing allergenicity of soy protein isolate for
      infant formula evaluated by ELISA and proteomics via Chinese soy-allergic
      children's sera.
AB  - Proteomics was used to confirm allergen subunit differences between control and
      high hydrostatic pressure (HHP)-treated soy protein isolate (SPI), which could
      support further understanding of reduced allergenicity associated with HHP. SPI
      solutions (0.75% protein weight/solvent volume, pH 6.8) were subjected to HHP
      treatment at 200, 300, 400, 500 MPa for 5, 10, 15, 20 min, respectively. Enzyme
      linked immunoabsorbent assay was used to assess the allergenicity, using soy
      allergic human sera as the probe and non-soy-allergic human sera as the negative
      control. Proteomics was performed to analyze allergen differences in a mixed
      protein sample. HHP reduced allergenicity by 45.5% at 300 MPa for 15 min. Western
      blotting and mass spectrometry indicated that HHP treatment altered the
      allergenicity of <alpha> and <alpha>' subunits of 7S globulin and A1 and A1a
      subunits of 11S globulin. This suggests HHP could improve the safe use of SPI in
      infant formula.

PMID- 30100441
TI  - Spermine and spermidine are cytotoxic towards intestinal cell cultures, but are
      they a health hazard at concentrations found in foods?
AB  - Spermine and spermidine are polyamines (PA) naturally present in all organisms,
      in which they have important physiological functions. However, an excess of PA
      has been associated with health risks. PA accumulates at quite high
      concentrations in some foods, but a quantitative assessment of the risk they pose
      has been lacking. In the present work, the cytotoxicity of spermine and
      spermidine was evaluated using an in vitro human intestinal cell model, and
      employing real-time cell analysis. Both spermine and spermidine showed a dose
      dependent cytotoxic effect towards the cultured cells, with necrosis the mode of
      action of spermidine and perhaps also that of spermine. Spermine was more
      cytotoxic than spermidine, but for both PA the concentrations found to be toxic
      were above the maximum at which they have been found in food. The present results
      do not, therefore, support the idea that spermine or spermidine in food is
      harmful to healthy people.

PMID- 30100442
TI  - Effects of casein micellar structure on the stability of milk protein-based
      conjugated linoleic acid microcapsules.
AB  - The effects of casein micellar structure on the stability of milk protein-based
      conjugated linoleic acid (CLA) microcapsules were investigated. CLA emulsions
      were prepared with milk protein concentrates (MPC) or a mixture of whey protein
      isolates (WPI) and sodium caseinate (SC). Larger droplet sizes and wider size
      distributions were observed for MPC-CLA emulsions, where the varied sizes and
      heterogeneous protein particles with different rigidity discontinuously adsorbed
      on the oil droplets. Aggregated oil droplets with porous walls were found on the
      inner surface of MPC-CLA spray-dried powders. These microcapsules also had lower
      encapsulation efficiency and unfavorable oxidative stability. For MPC-CLA, 17% of
      the CLA remained after 45 days at 35  degrees C, while ~80% was retained for the
      WPI+SC-CLA microcapsules. The adverse effect of the casein micellar structure
      suggested that modification of casein micelles will be needed to improve the
      efficiency and chemical stability of such microcapsules.

PMID- 30100443
TI  - Effect of thermal liquefying of crystallised honeys on their antibacterial
      activities.
AB  - Thermal liquefying of crystallised honey is the most convenient option for
      beekeepers to fully liquefy honey. A controlled mild thermal treatment is widely
      used for effective and safe liquefying of crystallised honey. In this study, we
      demonstrated that thermal liquefying at different temperatures of 45, 55 and 65 
      degrees C does not affect the overall honey antibacterial activity against
      Pseudomonas aeruginosa and Staphylococcus aureus, and, in some cases, it may even
      increase the antibacterial potential of honey. A mild thermal treatment of
      crystallised honey was able to significantly increase its glucose oxidase (GOX)
      enzyme activity. On the other hand, the increased GOX activity in treated honey
      samples did not affect levels of accumulated H2O2, suggesting that some
      phytochemicals may contribute to or modulate antibacterial activity. Taken
      together, a mild thermal liquefaction of crystallised honey may increase the
      potential bioactivity of this matrix, which is also affected by the botanical
      origin.

PMID- 30100444
TI  - Suppression of the formation of furan by antioxidants during UV-C light treatment
      of sugar solutions and apple cider.
AB  - Furan, which has been identified as a carcinogenic risk for humans, can be
      induced in different foods by UV-C light. In this study, we hypothesized that
      furan was produced by a UV light-induced free radical mechanism and antioxidants
      could suppress its formation. Our results demonstrated that, by adding
      antioxidants, such as butylated hydroxyl toluene, ascorbic acid or gallic acid,
      to simulated juice or apple cider during UV-C treatment, amounts of furan were
      significantly reduced. For example, the concentration of furan produced in apple
      cider by UV-C at 9.0 J/cm2 was 636 ppb but was less than 20 ppb with 0.25 ppm
      butylated hydroxyl toluene present, less than 3 ppb with 0.5% (w/v) ascorbic
      acid, and less than 1.0 ppb with 0.5% (w/v) gallic acid. These findings confirmed
      that antioxidants can be used as a safe and simple mitigation measure to control
      furan production in fruit drinks exposed to UV-light.

PMID- 30100445
TI  - Investigation on the formations of volatile compounds, fatty acids, and gamma
      lactones in white and brown rice during fermentation.
AB  - Volatile compounds, including gamma-lactones, in brown and white rice fermented
      by Lactobacillus paracasei, were compared using gas chromatography-mass
      spectrometry (GC-MS) with stir-bar sorptive extraction (SBSE). The contents of
      most esters, alcohols, lactones and some aldehydes were higher in brown rice
      samples containing higher amount of free fatty acids after fermentation. In
      particular, the contents of gamma-lactones increased more in fermented brown rice
      containing high amounts of fatty acids than in fermented white rice, suggesting
      that gamma-decalactone and gamma-nonalactone were formed from oleic acid and
      linoleic acid during rice fermentation. In addition, the contents of gamma
      decalactone in fermented brown rice samples with added 4-hydroxydecanoic acid and
      ricinoleic acid were determined. The content of gamma-decalactone in fermented
      brown rice samples with added 4-hydroxydecanoic acid was considerably higher than
      that in the control after fermentation, indicating that 4-hydroxydecanoic acid
      could be an effective intermediate for the formation of gamma-decalactone in rice
      during fermentation.

PMID- 30100446
TI  - Naringenin, a common flavanone, inhibits the formation of AGEs in bread and
      attenuates AGEs-induced oxidative stress and inflammation in RAW264.7 cells.
AB  - Dietary flavonoids as popular food additives have attracted a wide range of
      research interests. Naringenin, a common flavanone, was evaluated of its impact
      on the formation of advanced glycation endproducts (AGEs) in bread crust. It was
      found that with the increase of naringenin content in bread (0.25-1% w/w), the
      formation of CML and total fluorescent AGEs were significantly inhibited (9.67
      54.27% and 11.79-35.19%, respectively). In addition, the fortification with
      naringenin could also significantly inhibit the formation of acrylamide in bread
      crust, while enhancing the antioxidant and antibacterial activity of bread crumb
      without bringing undesirable changes to the bread quality attributes. Moreover,
      in RAW264.7 cells, naringenin significantly reduced of AGEs-induced ROS
      production as well as the contents of some inflammatory mediators. Altogether,
      our finding indicated naringenin can have dual inhibitory effects on both AGEs'
      formation in foods and AGEs-induced cellular oxidative stress and inflammation.

PMID- 30100447
TI  - Polyphenols in carobs: A review on their composition, antioxidant capacity and
      cytotoxic effects, and health impact.
AB  - Carob (Ceratonia Siliqua L., tree of the pea family Fabaceae) and its products
      have recently attracted great interest due to their polyphenolic composition.
      This review summarizes the polyphenolic compounds that are contained in different
      carob parts (leaves, pod, seeds, barks) and products (syrup, flour, fiber). It
      also states the main differences of polyphenolic composition due to environmental
      and natural reasons, such as region, variety, and gender, and due to the
      processes used for preparation, extraction and analysis. The gender, along with
      the extraction procedure, proved to be the most important factors affecting the
      polyphenolic composition. Supercritical fluid extraction is the most efficient
      technique used because it protects polyphenols from decomposition. Due to the
      relatively low number of publications, it is concluded that further development
      of optimum methods for extraction, analysis and isolation of polyphenols should
      be carried over to assess their antioxidant capacity and their food technological
      and pharmaceutical industry.

PMID- 30100448
TI  - Rapid detection of beta-conglutin with a novel lateral flow aptasensor assisted
      by immunomagnetic enrichment and enzyme signal amplification.
AB  - A simple, rapid and economic lateral flow immunochromatographic assay (LFICA) was
      designed for ultrasensitive detection of beta-conglutin. Instead of antibodies
      and gold nanoparticles (AuNPs) used in conventional LFICA, a cognate aptamer duo,
      binding to beta-conglutin and Fe3O4@Au core-shell nanoparticles, was applied in
      this study. An enzyme signal amplification strategy was used to enhance
      sensitivity. In addition, a new magnetic enrichment strategy was employed to
      further enhance sensitivity of the assay, slowing down movement of the capture
      probe (i.e., Fe3O4@Au nanostructures) using an external magnetic field. The novel
      LFICA assay can be completed within 20 min and achieved a detection limit of 8
      fM, a thousand-times lower than similar assays without magnetic focusing.
      Overall, our results demonstrated the potential for the proposed LFICA sensor in
      rapid detection of beta-conglutin without any special analytical expertise or
      instrumentations.

PMID- 30100449
TI  - Effects on chlorophyll and carotenoid contents in different grape varieties
      (Vitis vinifera L.) after nitrogen and elicitor foliar applications to the
      vineyard.
AB  - Photosynthetic pigments, including carotenoids are important secondary
      metabolites, which play a key role in photosynthesis. There is little information
      about the effects of nitrogen and elicitor applications on chlorophyll and
      carotenoid concentrations in grapes. The aim of this work was therefore to study
      the effects of the foliar application of nitrogen sources and elicitors to
      Tempranillo, Garnacha and Graciano (Vitis vinifera L.) grapevines on chlorophyll
      and carotenoid contents. The results showed that beta-carotene and lutein were
      the most abundant carotenoids in all the samples, ranging from 1336 and 227 to
      7054 and 1382 MUg/g, respectively. The applied treatments had greater impact on
      chlorophyll and carotenoid contents in Tempranillo grapes than in Graciano and
      Garnacha varieties. The content of chlorophyll was determined by the variety
      factor, while the concentration of carotenoids was influenced by the interaction
      of variety and treatment factors, depending on the type of foliar application.

PMID- 30100450
TI  - Upgrading the antioxidant properties of fucoidan and alginate from Cystoseira
      trinodis by fungal fermentation or enzymatic pretreatment of the seaweed biomass.
AB  - The seaweed Cystoseira trinodis was fermented by different fungi prior to
      extraction of fucoidan and alginate to enhance their antioxidative potential. All
      the investigated fungi were able to produce fucoidanase (1.05-3.41 U/ml) and
      alginate lyase (7.27-18.59 U/mL). Different fungal species induced a reduction in
      the molecular weight (MW) of fucoidan and alginate in comparison to the
      unfermented control. The MW of fucoidan reduced by 41-81.5%, while the MW of
      alginate was reduced by 28-75%, depending on the fungal species. Significant
      increases in the fucose and sulphate contents of fucoidan and
      mannuronic/guluronic acid ratio of alginate were induced by fungal fermentation.
      Fungal pretreatment enhanced the ferric reducing antioxidant power, total
      antioxidant capacity and hydroxyl radical scavenging activity of both fucoidan
      and alginate. Additionally, enzymatic pretreatment of the macroalgal biomass
      assisted in the recovery of fucoidan and alginate with low molecular weight and
      enhanced antioxidative potential.

PMID- 30100451
TI  - Trapping of glyoxal by propyl, octyl and dodecyl gallates and their mono-glyoxal
      adducts.
AB  - Glyoxal (GO) is one of the major toxic intermediates generated during lipid
      oxidation and degradation. We investigated the inhibitory activities and
      mechanisms of propyl, octyl, and dodecyl gallates (PG, OG, and DG) on the
      formation of GO in buffer and during thermo-processing of corn oil, and the anti
      carbonyl and antioxidative activities of the mono-GO adducts of PG, OG, and DG.
      Our results suggested that alkyl gallates could more effectively trap GO than
      gallic acid. The major mono-GO adducts of PG, OG, and DG were purified and their
      structures were elucidated based on their 1H, 13C, 2D-NMR, and HRMS data. We
      further demonstrated that the mono-GO (MG) adducts retained the anti-carbonyl and
      antioxidative activities. This is the first study to demonstrate that alkyl
      gallates, the popular food additives, could prevent not only food oxidation, but
      also the formation of toxic reactive carbonyl species and their corresponding
      advanced glycation end products (AGEs) during food processing.

PMID- 30100452
TI  - Soybean ultrasound pre-treatment prior to soaking affects beta-glucosidase
      activity, isoflavone profile and soaking time.
AB  - Ultrasound may convert conjugated isoflavones into their corresponding aglycones,
      the best form for absorption in the human body. However, ultrasound may also
      influence the activity of endogenous beta-glucosidase. Therefore, the present
      work evaluated the effects of soybean ultrasound pre-treatment by applying the
      Box-Behnken design prior to soaking, a step that is important for industries to
      prepare certain soy products. Furthermore, a multi-response optimisation is
      provided. The best conditions for soybean ultrasound pre-treatment were
      established as temperature, X1 = 55  degrees C; exposure time, X2 = 5 min and
      ultrasound intensity, X3 = 19.5 W cm-2. Under these conditions, soybeans with
      higher contents of aglycones were obtained and beta-glucosidase activity was kept
      as high as possible. A second experiment was conducted and confirmed that
      ultrasound pre-treatment results in a lower soaking time (2 h) to achieve the
      highest moisture content, lower hardness as well as increased content of
      aglycones.

PMID- 30100454
TI  - Black goji as a potential source of natural color in a wide pH range.
AB  - Lycium ruthenicum Murr. is a traditional Chinese herb widely distributed in
      Tibet. The fruit, known as black goji, is popular in traditional Chinese
      medicine. The objective of this study was to investigate its anthocyanin profile
      (by HPLC coupled to PDA and MS detectors) and the colorimetric and
      spectrophotometric properties. Black goji extracts contained abundant petunidin
      derivatives, with cis and trans isomers of petunidin-3-p-coumaroyl-rutinoside-5
      glucoside. The colorimetric and spectrophotometric traits of black goji
      anthocyanins were significantly impacted by solid-phase-extraction, pH, and
      acylation. MCX cartridge removed considerable polyphenolics from fruit extracts,
      but attenuated the saturation of color expression. Petunidin-3-trans-p-coumaroyl
      rutinoside-5-glucoside contributed most of the color expression of the black goji
      extract, and showed superior stability compared to other extracts over time.
      Acylation strengthened the petunidin derivatives color retention, and enhanced
      the color intensity and stability. Black goji anthocyanins produced various vivid
      hues over wide ranges of pH, making them promising candidates for natural
      colorants.

PMID- 30100453
TI  - Application of magnetic N-doped carbon nanotubes in solid-phase extraction of
      trace bisphenols from fruit juices.
AB  - Magnetic N-doped carbon nanotubes were firstly applied as adsorbent in food
      analysis for pre-concentration of bisphenols in fruit juices followed by ultra
      high performance liquid chromatography-tandem mass spectrometry determination.
      The magnetic nanoparticles were characterized by X-ray diffraction, infrared
      spectroscopy, scanning electron microscopy and vibrating sample magnetometer. The
      adsorption conditions were further optimized by response surface methodology.
      Under optimal conditions, the method provided good linearity with correlation
      coefficient (r >= 0.9979), excellent intermediate precisions (2.71-5.91%, n = 3),
      low limits of detection (LODs) ranging from 0.43 to 2.47 ng L-1, and satisfying
      recoveries of three juice samples (between 90.6% and 101%).

PMID- 30100455
TI  - Label-free proteomic strategy to compare the proteome differences between
      longissimus lumborum and psoas major muscles during early postmortem periods.
AB  - Beef M. longissimus lumborum (LL) and M. psoas major (PM) muscles showed
      significant differences in various meat quality attributes (such as pH, lipid
      oxidation, and color stability). To better understand the underlying molecular
      variations between LL and PM, the proteome changes at early postmortem periods
      were investigated by comparative proteomic approach. A total of 504, 519, and 487
      mutual proteins of each comparison (LL vs. PM at 1 h, 12 h, and 24 h,
      respectively) were successfully identified. Among these proteins, 238 proteins
      were differentially expressed in LL samples compared to PM ones. Proteins
      involved in glycolysis and with functions of protection and repair were
      overabundant in LL, whereas those participating in tricarboxylic acid (TCA)
      cycle, oxidative phosphorylation, and fatty acid beta-oxidation were overabundant
      in PM. Furthermore, the bioinformatics analyses provided insightful information
      for explaining the differences in meat quality traits between LL and PM, and for
      further metabolomics studies.

PMID- 30100456
TI  - Covalent binding of food-derived blue pigment phycocyanobilin to bovine beta
      lactoglobulin under physiological conditions.
AB  - In this study, we investigated structural aspects of covalent binding of food
      derived blue pigment phycocyanobilin (PCB) to bovine beta-lactoglobulin (BLG),
      major whey protein, by spectroscopic, electrophoretic, mass spectrometry and
      computational methods. At physiological pH (7.2), we found that covalent pigment
      binding via free cysteine residue is slow (ka = 0.065 min-1), of moderate
      affinity (Ka = 4 * 104 M-1), and stereo-selective. Binding also occurs at a broad
      pH range and under simulated gastrointestinal conditions. Adduct formation rises
      with pH, and in concentrated urea (ka = 0.101 min-1). The BLG-PCB adduct has
      slightly altered secondary and tertiary protein structure, and bound PCB has
      higher fluorescence and more stretched conformation than free chromophore.
      Combination of steered molecular dynamic for disulfide exchange, non-covalent and
      covalent docking, favours Cys119 residue in protein calyx as target for covalent
      BLG-PCB adduct formation. Our results suggest that this adduct can serve as
      delivery system of bioactive PCB.

PMID- 30100457
TI  - In vitro assessment of bioavailability of selenium from a processed Japanese
      anchovy, Niboshi.
AB  - Niboshi is a commonly used foodstuff that is processed from Japanese anchovy
      (Engraulis japonicus) in Japanese cuisine. It was previously demonstrated that
      Niboshi and its water extract contained highly bioavailable selenium for selenium
      deficient mice. In this study, we assessed the selenium bioavailability from the
      extract of the Niboshi, using cultured cells. The activity of selenium-dependent
      glutathione peroxidase (GPx) of rat dorsal ganglion cells and human cervical
      carcinoma cells incubated with selenium from the Niboshi extract was over 2 times
      of that of the extract-free control cells and comparable to that of cells
      incubated with selenious acid of the same selenium concentration. These results
      suggest that selenium from the Niboshi extract was utilized for synthesis of the
      selenoprotein. Such in vitro selenium bioavailability was consistent with our
      previous results of in vivo assessment in mice.

PMID- 30100458
TI  - Development of a liquid chromatography-tandem mass spectrometry method with
      modified QuEChERS extraction for the quantification of mebendazole and its
      metabolites, albendazole and its metabolites, and levamisole in edible tissues of
      aquatic animals.
AB  - A liquid chromatography-tandem mass spectrometry quantitative method was
      developed for determining mebendazole and its metabolites, albendazole and its
      metabolites, and levamisole in muscles of bluntnose black bream, shrimp, eel and
      turtle based on modified QuEChERS methodology. The method included 2 g of the
      muscle matrix with 10 mL acetonitrile, and 0.8 g of magnesium sulphate and 0.2 g
      of sodium chloride for liquid-liquid partitioning. After vortex and
      centrifugation, the resulting liquid (5.5 mL) was purified by C18 (50 mg) and Al
      N (50 mg). The limits of detection were lower than 0.3 MUg kg-1 and the limits of
      quantitation were no more than 1 MUg kg-1 for all analytes. The recoveries of the
      analytes ranged from 80.0% to 113.7% with the relative standard derivation less
      than 10.0%. The preparation procedure provided efficient extraction and
      purification that enabled a sensitive and rugged determination of target
      compounds.

PMID- 30100459
TI  - Isolation and identification of the main carotenoid pigment from a new variety of
      the ridgetail white prawn Exopalaemon carinicauda.
AB  - The ridgetail white prawn (Exopalaemon carinicauda) is an important economic
      species in China. In order to know the molecular basis and evaluate the potential
      nutrition value of a new variety of this species with orange-red color, the main
      carotenoid pigments were extracted and identified through high performance liquid
      chromatography. It showed that higher concentration of free astaxanthin existed
      in the new variety which might cause the color variation. The concentration of
      total astaxanthin in muscle and waste of the new variety was 3.3 and 1.9 fold
      higher than that in natural prawn under the same culture condition (P < 0.05).
      The predominant geometric and optical isomers of astaxanthin in muscle of the new
      variety were identified as all-trans and 3S,3'S astaxanthin. This is the first
      report of astaxanthin-enriched E. carinicauda, which also provides an alternative
      source of natural astaxanthin and the possibility for improving the nutrition
      value in this species.

PMID- 30100460
TI  - Let food be thy medicine and medicine be thy food: A bibliometric analysis of the
      most cited papers focusing on nutraceuticals and functional foods.
AB  - The current study aimed to identify and analyze the 100 most cited papers on the
      topic of nutraceuticals and functional foods. Scopus database was searched to
      extract bibliometric data. Two-thirds of the 100 most cited papers were reviews.
      Papers were mostly published in food science and nutrition journals, and one
      third were published in seven journals, namely: British Journal of Nutrition (6),
      Critical Reviews in Food Science and Nutrition (6), Journal of Food Science (5),
      Trends in Food Science and Technology (5), American Journal of Clinical Nutrition
      (4), Food Chemistry (4) and Journal of Nutrition (4). Topics with high citation
      counts dealt with prebiotics, probiotics, antioxidants and phenolic content. Hot
      topics with over 1000 citations per paper include bifidobacterium (1147), colon
      (1032) and lipid metabolism (1013). The United States and Europe were major
      places of origin. These results can serve as a quick benchmarking reference for
      researchers or general public members.

PMID- 30100461
TI  - Effect of lipid oxidation on the formation of Nepsilon-carboxymethyl-lysine and
      Nepsilon-carboxyethyl-lysine in Chinese-style sausage during storage.
AB  - This work aimed to investigate the effects of lipid oxidation on Nepsilon
      carboxymethyllysine (CML) and Nepsilon-carboxyethyllysine (CEL) formation in
      three types of Chinese-style sausages during storage. Medium-high temperature
      dried sausage, naturally dehydrated sausage and smoke-dried sausage were
      prepared, and CML/CEL contents were measured. The result showed that CML and CEL
      levels increased with the increasing storage time, and an exponential correlation
      was found between thiobarbituric acid reactive substances (TBARs) and either CML
      (r2 = 0.922) or CEL (r2 = 0.921) in medium-high temperature dried sausages and
      smoke-dried sausage, which suggested that lipid oxidation could facilitate
      CML/CEL formation during storage. Furthermore, lipid oxidation and the Maillard
      reaction might have a synergistic effect on CML formation in Chinese-style
      sausages, as evidence by the results of model system during incubation. These
      findings indicated that lipid oxidation played a key role in CML/CEL formation
      during the storage of Chinese-style sausages.

PMID- 30100462
TI  - Enhanced gamma-aminobutyric acid accumulation, alleviated componential
      deterioration and technofunctionality loss of germinated wheat by hypoxia stress.
AB  - Germination is an effective biofortification strategy to enhance micronutrients
      of staple grains. The current study targeted at comparing the effects of normoxia
      and hypoxia on gamma-aminobutyric acid (GABA) content and the componential
      changes underlying the technofunctionality of germinated wheat. Compared with
      ungerminated wheat, GABA maximumly enhanced by 88.73% and 50.70% in hypoxia- and
      normoxia-germinated wheat (HGW and NGW), respectively. Hypoxia suppressed the
      germination degree of wheat, which better preserved the technofunctionality.
      Compared with NGW, the proteolytic and alpha-amylase activities were partially
      inhibited for HGW, resulting in higher protein and starch content. The
      diminishment of gluten marcopolymers and soluble high-molecular-weight proteins,
      and conversion of alpha-helices to beta-turns were alleviated in HGW, which
      contributed to the more viscoelastic dough. Meanwhile, superior pasting and
      gelation properties were mainly due to suppressed alpha-amylase activity and more
      starch content in HGW. The results suggested that HGW flour can be exploited as a
      functional staple ingredient.

PMID- 30100463
TI  - The structure-antioxidant activity relationship of dehydrodiferulates.
AB  - In this study, 11 dehydrodiferulic acids (DFAs) and 8 diethyl dehydrodiferulates
      (DEFs) were synthesized and evaluated by Trolox equivalent antioxidant capacity
      (TEAC) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) assays for their antioxidant
      properties to understand the Structure-Antioxidant Activity Relationship (SAR) of
      these dehydrodiferulates. In both assays, the order of antioxidant activity for
      all tested ferulic acid dimers were consistent except for 3-(4-Hydroxy-3-methoxy
      benzylidene)-5-(4-hydroxy-3-methoxy-phenyl)-3H-furan-2-one (2, 8-8-lactone DC
      DFA, not occurred naturally) being the best antioxidant by TEAC test. The order
      of antioxidant activity of diferulic acid ethyl esters, evaluated by both assays,
      was not consistent; however, TEAC and DPPH assays provided consistent results for
      certain set of ethyl diferulates. In this study most of dimeric ferulates, with
      three exceptions, showed higher radical-scavenging efficacy than the monomers.
      Comparing the antioxidant activities of the tested diferulates suggested that the
      phenolic hydroxyl group, electron donating methoxyl group, and stable conjugated
      transient structures dictate the antioxidant activity of diferulates.

PMID- 30100464
TI  - Tetraplex real-time PCR assay for the simultaneous identification and
      quantification of roe deer, red deer, fallow deer and sika deer for deer meat
      authentication.
AB  - Analytical methods are needed for the identification and quantification of meat
      species to detect food adulteration. Since game meat is more expensive than meat
      from domesticated animal species, it is a potential target for adulteration. We
      present a tetraplex real-time PCR assay that allows the simultaneous
      determination of the content of roe deer, red deer, fallow deer and sika deer.
      The tetraplex assay showed only moderate cross-reactivity with closely related
      species. After optimization the tetraplex assay had a limit of detection of 0.1%
      (w/w) and a limit of quantification of 0.5% (w/w) for each of the four deer
      species. The tetraplex assay was found to be robust, slight modifications of the
      experimental setup did not lower its performance. Recoveries obtained by
      analyzing DNA mixtures and DNA isolates from model game sausages were similar to
      those obtained with the singleplex assays.

PMID- 30100465
TI  - Response surface methodology to optimize supercritical carbon dioxide/co-solvent
      extraction of brown onion skin by-product as source of nutraceutical compounds.
AB  - Food industry produces a large amount of onion wastes. Due to the high amount of
      bioactive compounds in onion by-products an idea for their reuse, could be use
      them as source of high-value functional and health ingredients. In this study,
      outer dry layers of coppery onion "Ramata di Montoro" were used as source of
      bioactive compounds. Firstly, the chemical profile of secondary metabolites of
      exhaustive extract, obtained by ultrasound assisted extraction was established by
      UHPLC-UV-HRMS/MS analysis. Subsequently, the supercritical fluid extraction was
      used as alternative and green method to recover flavonoids from onion skin. Main
      parameters such as pressure, temperature and composition of solvent modifier were
      optimized in order to improve the extraction efficiency of SFE technique, by
      using a response surface Box-Behnken design.

PMID- 30100466
TI  - Electrochemical DNA biosensor for potential carcinogen detection in food sample.
AB  - The presence of carcinogens in food is a major food safety concern. A
      nanocomposite-based electrochemical DNA biosensor was constructed for potential
      carcinogen detection in food samples by immobilizing amine terminated single
      stranded DNA onto silica nanospheres deposited onto a screen-printed electrode
      modified using gold nanoparticles. The effect of three different DNA sequences:
      15-base guanine, 24-base guanine and 24-base adenine-thymine rich DNA on
      carcinogen (formaldehyde and acrylamide) detection was evaluated. The competitive
      binding of the DNA with the carcinogen and electroactive indicator, Methylene
      blue (MB) was measured using differential pulse voltammetry. Optimization studies
      were conducted for MB concentration and accumulation time, DNA concentration,
      buffer concentration, pH and ionic strength. Overall, the 24-base guanine rich
      DNA yielded the best results with a detection limit of 0.0001 ppm, linear range
      between 0.0001 ppm and 0.1 ppm and reproducibility below 5% R.S.D. Finally, the
      results obtained using the biosensor were validated using Ames test.

PMID- 30100467
TI  - Contribution of myofibril filament disassembly to textural deterioration of ice
      stored grass carp fillet: Significance of endogenous proteolytic activity, loss
      of heat shock protein and dephosphorylation of myosin light chain.
AB  - To investigate the underlying mechanism of softening of ice-stored grass carp
      fillet, changes in assembly structure of myofibrillar proteins and potential
      candidates for regulating this change including myosin regulatory chain
      phosphorylation, heat shock proteins (Hsp27, Hsp90, alphaB-crystallin and UNC45)
      and endogenous protease activity were studied. Comparison of SDS-PAGE pattern of
      myofibrillar proteins treated with EDC crosslinking showed that thin filament
      experienced rapid disassembly within initial 8 h, followed by depolymerization of
      thick filament consisting of myosin, which further exacerbated the myofibril
      disorganization of fillets. Pearson coefficient analysis showed that UNC45,
      Hsp90, Hsp27 and alphaB-crystallin concentration and cathepsin B, D, L activities
      were significantly correlated with dissociated MHC and actin. Therefore, the
      significant correlation between shear force and dissociated MHC and actin clearly
      demonstrated that post mortem disassembly of myofibril filaments, which was
      regulated by endogenous proteolytic activity and loss of Hsp, contributed to the
      softening of ice-stored grass carp fillets.

PMID- 30100468
TI  - CO2 enrichment can enhance the nutritional and health benefits of parsley
      (Petroselinum crispum L.) and dill (Anethum graveolens L.).
AB  - The functional food value of herbal plants is greatly related to their contents
      of valuable phytochemicals. Regarding its impact on primary and secondary plant
      metabolism, CO2 enrichment could be a candidate strategy to modulate the levels
      of nutritionally and medicinally interesting phytochemicals in herbal plants.
      Herein, the concentrations of 81 metabolites and minerals were evaluated in shoot
      tissues of parsley and dill grown under two levels of CO2, ambient (378 +/- 25
      umole CO2 mole-1 air, aCO2) and elevated (627 +/- 24 umole CO2 mole-1 air, eCO2).
      Regardless of the plant species, eCO2 improved the levels of soluble sugars,
      starch, organic acids, some EAAs, most of USFA, total phenolics, total flavonoids
      and vitamins A and E. However, notable variations in the metabolites
      responsiveness to eCO2 were recorded among the tested plant species. Moreover,
      considerable improvements in the total antioxidant capacity, antiprotozoal,
      antibacterial and anticancer activities were recorded for parsley and dill in
      response to eCO2.

PMID- 30100469
TI  - Sample preparation and determination of pesticides in fat-containing foods.
AB  - Pesticides are still a very important factor in food plant cultivation. The
      lipophilic character of most pesticides can lead to their accumulation in fat,
      which can have harmful effects on humans and animals. The aim of this review is
      to present current knowledge about the isolation and determination of pesticides
      in fatty commodities. The following techniques for isolation are discussed:
      solvent partitioning, solid phase and dispersive solid phase, QuEChERS-based
      procedures, matrix solid-phase dispersion, gel permeation chromatography, Soxhlet
      extraction, accelerated solvent extraction, and microextraction techniques.
      Chromatographic methods predominate in the analysis of pesticide residues in
      fatty matrices and, for this reason, the review focuses on these methods,
      particularly those combined with mass spectrometry. Analytical chemists still
      face the challenge - in the determination of pesticide residues in fatty matrices
      - of developing simpler and quicker procedures that consume less organic
      solvents.

PMID- 30100470
TI  - Discovery of taste modulating octadecadien-12-ynoic acids in golden chanterelles
      (Cantharellus cibarius).
AB  - Activity-guided fractionation in combination with taste dilution and comparative
      taste dilution analysis, followed by LC-MS and 1D/2D-NMR experiments, enabled the
      identification of several C18-acetylenic acids in chanterelles among which
      (9Z,15E)-14,17,18-trihydroxy-9,15-octadecadien-12-ynoic acid, (9Z,15E)-14-oxo
      9,15-octadecadien-12-ynoic acid, (10E,15E)-9-hydroxy-14-oxo-10,15-octadecadien-12
      ynoic acid, (10E,15E)-9-hydroperoxy-14-oxo-10,15-octadecadien-12-ynoic acid,
      (10E,15E)-9,14-dioxo-10,15-octadecadien-12-ynoic acid, (9Z,15E)-14-oxo-9,15
      octadecadien-12-ynoic acid methyl ester, (9Z,15E)-17(18)-epoxy-14-oxo-9,15
      octadecadien-12-ynoic acid methyl ester and (10E,14Z)-9-hydroperoxy-10,14
      octadecadien-12-ynoic acid have not yet been reported in literature. Sensory
      evaluation in a basic taste recombinant revealed taste modulating thresholds for
      the octadecadien-12-ynoic acids in the range of 19-105 umol/l. In comparison,
      three isolated octadecadienoic acids, namely (10E,14Z)-12-hydroxy-10,14
      octadecadienoic acid, (9Z,11Z)-14,18-dihydroxy-9,11-octadecadienoic acid, and
      (9Z,11Z)-14,17,18-trihydroxy-9,11-octadecadienoic acid, respectively, did not
      show any taste modulating activity, thus pinpointing the putative key role of the
      acetylene moiety for kokumi enhancement.

PMID- 30100471
TI  - Quantitative analysis of chloramphenicol, thiamphenicol, florfenicol and
      florfenicol amine in eggs via liquid chromatography-electrospray ionization
      tandem mass spectrometry.
AB  - A widely applicable method involving liquid chromatography-electrospray
      ionization tandem triple quadrupole mass spectrometry (LC-ESI/MS/MS) was
      developed for the simultaneous determination of chloramphenicol, thiamphenicol,
      florfenicol, and florfenicol amine in eggs. Samples were extracted with ethyl
      acetate-acetonitrile-ammonium hydroxide (49:49:2, v/v) and defatted with hexane
      saturated with acetonitrile. The analysis was carried out on a mass spectrometer
      via an electrospray interface operated in the positive and negative ionization
      modes using deuterated chloramphenicol-d5 as the internal standard. The limits of
      detection and limits of quantification were 0.04-0.5 MUg/kg and 0.1-1.5 MUg/kg in
      eggs, respectively. The average recoveries of the four analytes from egg samples
      were 90.84-108.23%, with relative standard deviations of less than 9.61%. The
      corresponding intra-day and inter-day variations were found to be less than 8.11%
      and 11.30%, respectively. Finally, the new approach was successfully applied to
      the quantitative determination of these analytes in 50 commercial eggs from local
      supermarkets.

PMID- 30100472
TI  - Comparison of quantitative methods based on SYBR Green real-time qPCR to estimate
      pork meat adulteration in processed beef products.
AB  - Quantitative real-time PCR (qPCR) is a modern technique that has been widely used
      for the detection of species used in meat products. For obtaining accurate and
      reliable qPCR results, we assessed two common DNA quantification methods for
      isolated DNA and five quantification approaches for qPCR products. DNA dilution
      based on spectrofluorometric results showed better qPCR results than those based
      on spectrophotometry in terms of linear correlation, amplification efficiency,
      and linear dynamic range. Binary pork-beef mixtures were used to construct
      standard curves of SYBR Green-based qPCR products using five quantification
      approaches, and they were validated and compared using in-house pork models. 18S
      rRNA gene normalization methods showed better trueness (-11.79% to -6.73%) than
      that of methods using absolute and relative standard curves (-28.52% to -18.64%)
      in a model burger. These normalized reference methods successfully estimated the
      quantities of pork meat in the range of 100%-0.01% in commercial beef products.

PMID- 30100473
TI  - NMR-based global metabolomics approach to decipher the metabolic effects of three
      plant growth regulators on strawberry maturation.
AB  - Plant growth regulators (PGRs) are commonly used to regulate maturation in
      strawberry. Despite this, comprehensive assessments of the metabolomic effects of
      PGRs on strawberry maturation are lacking. In this study, a nuclear magnetic
      resonance-based approach, combined with multivariate and pathway analysis, was
      used to evaluate the regulatory effects of gibberellin, forchlorfenuron, and
      brassinolide, applied at two different maturation stages, on the expression of
      metabolites in strawberry. The results demonstrated that the PGRs differentially
      influenced metabolism, whether applied at the same or different maturation
      stages. Additionally, we also discovered that these different PGRs exhibited some
      similar metabolic trends when applied at the same growth period. Our findings
      validate the use of NMR-based metabolomics for identifying subtle changes in the
      expression of metabolites associated with PGR application.

PMID- 30100474
TI  - Development and quality assessment of a turbid carrot-orange juice blend
      processed by UV-C light assisted by mild heat and addition of Yerba Mate (Ilex
      paraguariensis) extract.
AB  - Carrot-orange juice processed by UV-C (10.6 kJ/m2) assisted with mild heat (H, 50
      degrees C) and yerba mate addition (E) was obtained. UV-C/H + E treated juice
      was examined for native flora, polyphenol content (PC), total antioxidant
      activity (TAA), colour, turbidity,  degrees Brix and pH along storage (4  degrees
      C). Consumer profiling studies were performed. UV-C/H + E provoked 2.6-5.7 native
      flora log reductions, preventing from recovery during 24 day-storage. The UV-C/H
      + E juice exhibited a significant increase in PC (720.2 ug/mL) and TAA (5.5
      mg/mL) compared to untreated (PC = 205.0 ug/mL/TAA = 0.7 mg/mL) and single
      treated juices (PC = 302.1-408.0 ug/mL/TAA = 0.7-2.4 mg/mL), remaining constant
      throughout storage. UV-C/H + E juice exhibited scarce changes in colour.
      Nevertheless, increases in  degrees Brix and turbidity were observed compared to
      single treatments. A cluster sensory analysis revealed that one group showed a
      marked interest in UVC/H + E beverages with herbal taste and strong aroma. CATA
      question revealed that some improvements should be introduced in order to satisfy
      the consumers' ideally beverage.

PMID- 30100475
TI  - The stability of three different citrus oil-in-water emulsions fabricated by
      spontaneous emulsification.
AB  - In this study, emulsions were prepared through spontaneous emulsification, using
      three different citrus oils as the oil phase and Tween 80 as the surfactant.
      Utilizing 4% Tween 80, three types of citrus oil emulsions were prepared with
      small particle size, monomodal distribution and high transmission. After 24 h,
      each emulsion exhibited different degrees of gravitational separation. Mandarin
      oil emulsions were the most unstable, showing coalescence of small droplets with
      an obvious cream layer formed at 9 h. Bergamot oil emulsions possessed small
      droplets with the best stability over 24 h, due to their relatively polar
      components (e.g. linalyl acetate) and water-insoluble constituents (e.g. gamma
      terpinene). These results suggest that the emulsifying properties and instability
      mechanism of citrus oil emulsions are strongly dependent on the inherent
      properties and composition of citrus oils. This study is significant for the
      development of an effective strategy to improve the stability of citrus oil-based
      colloidal systems.

PMID- 30100476
TI  - Identification of a freshness marker metabolite in stored soybean sprouts by
      comprehensive mass-spectrometric analysis of carbonyl compounds.
AB  - The objective of this study was to identify metabolites that quantitatively
      indicate degrees of freshness of soybean sprouts. Self-cultivated soybean sprouts
      were stored at 5  degrees C, 10  degrees C or 20  degrees C, and respiratory CO2
      production rates were monitored using gas chromatography during storage. Carbonyl
      compounds (CCs) were analyzed comprehensively using mass-spectroscopic
      metabolomics analyses. CCs were derivatized using dansyl hydrazine (DH) and were
      then analyzed using high performance liquid chromatography-electrospray
      ionization tandem mass spectrometry (HPLC-MS/MS) with multiplexed multiple
      reaction monitoring (MRM). In the MRM chromatogram, 171 to 358 peaks were
      observed from stored soybean sprouts. Principle component analysis and
      discriminant analysis (PCA-DA) selected the CC-DH derivative ion with a m/z 512
      at a retention time of 9.34 min as the most significant metabolite. Searching
      online metabolomics databases and matching fragment patterns of product ion mass
      spectra of an authentic standard revealed abscisic acid is a freshness marker of
      soybean sprouts.

PMID- 30100477
TI  - SREBP1, PPARG and AMPK pathways mediated the Cu-induced change in intestinal
      lipogenesis and lipid transport of yellow catfish Pelteobagrus fulvidraco.
AB  - Cu could act as a modifier and influence lipid metabolism, but the potential
      mechanism was not explored. Juvenile yellow catfish were fed diet containing 0.71
      (low Cu), 3.93 (intermediate Cu) and 88.81 (high Cu) mg Cu kg-1, for 8 weeks to
      explore the modulation of intestinal lipid metabolism following dietary Cu
      addition. Using specific pathway inhibitors (Fatostatin for SREBP1, T0070907 for
      PPARG and Compound C for AMPK), primary enterocytes of yellow catfish were used
      to explore the molecular mechanisms of Cu reducing intestinal lipid deposition.
      Dietary Cu addition triggered Cu accumulation but suppressed lipid deposition in
      the fore- and mid-intestine. The reduced lipid deposition was attributable to the
      suppressed lipogenesis and lipid absorption, and accelerated lipid transport. The
      PPARG, SREBP1 and AMPK signaling pathways mediated the Cu-induced changes in
      lipogenesis, lipid uptake and lipid transport in the intestine of yellow catfish.

PMID- 30100478
TI  - Spray-dried polyphenolic extract from Italian black rice (Oryza sativa L., var.
      Artemide) as new ingredient for bakery products.
AB  - Artemide is one of the Italian pigmented rice varieties richest in polyphenols,
      especially anthocyanins. The aim of this work was to obtain anthocyanin-rich
      powders from Artemide cv, useful as functional ingredients for bakery foods. The
      hydroalcoholic extract prepared from Artemide black rice was processed by both
      spray-drying (with and without coating agents: maltodextrins: MD; arabic gum: GA)
      and freeze drying, in order to obtain ingredients more stable during storage and
      baking. The polyphenols spray-dried with MD and GA (50:50, w/w) resulted the
      ingredient most stable to the storage and partially protected from thermal damage
      during the baking in a model biscuit. The enriched biscuits showed a
      significantly higher content of polyphenols, antioxidant capacity and
      anthocyanins respect to a control biscuit. The polyphenolic extract obtained from
      Artemide black rice can be considered a valuable source of polyphenols to produce
      functional foods or microencapsulated ingredients for nutraceutical applications.

PMID- 30100479
TI  - Digestive aspartic proteases from sabalo (Prochilodus lineatus): Characterization
      and application for collagen extraction.
AB  - Acid proteases from sabalo stomach mucosa were recovered using salting-out
      procedure. This single step produced an enzyme extract purified 1.8-fold over the
      crude extract with a recovery of 45.1% of its initial proteolytic activity.
      Sabalo proteases exhibited the highest activity at 45  degrees C-pH 2.0, showed
      pH stability between 2.0 and 5.0 and retained more than 70% of its activity after
      incubation at pH 7.0 for 2 h. Fish extract was unstable at temperatures greater
      than 45  degrees C. Its activity was inhibited by pepstatin A but not by PMSF,
      while EDTA and SDS showed partial inhibitory effects. Presence of CaCl2 and MgCl2
      increased the proteolytic activity, while increasing concentrations of NaCl
      strongly decreased it. In addition, compared to the acid extraction method, the
      use of sabalo enzymatic extract increased 1.7 times the yield of collagen
      extraction.

PMID- 30100480
TI  - Antioxidant and antidiabetic activity of blackberry after gastrointestinal
      digestion and human gut microbiota fermentation.
AB  - Blackberry fruit contains high levels of polyphenols particularly anthocyanins
      which contribute to its biological activities. Bioavailability of polyphenols
      especially anthocyanins is generally low, it has been proposed that metabolites
      from polyphenol biotransformation under colonic fermentation are components that
      exert health benefits. In this study, blackberry was subjected to simulated
      gastrointestinal digestion and gut microbiota fermentation at different time
      intervals (0-48 h) to study the changes in bioactive components, its antioxidant
      and antidiabetic activities. Phenolic compounds, during digestion and
      fermentation were also analysed. Gut metabolites of blackberry significantly
      increased the glucose consumption and glycogen content in HepG2 cells.
      Furthermore, gut metabolites ameliorated high glucose plus palmitic acid-induced
      ROS overproduction, mitochondrial membrane collapse, and glutathione depletion in
      HepG2 cells. The mechanism of antidiabetic activity of blackberry was via its
      potent antioxidant activity. Therefore, our results suggest that blackberry could
      be recommended as a functional food due to potential antioxidant and antidiabetic
      activity.

PMID- 30100481
TI  - Kinetic study of high-intensity ultrasound-assisted Maillard reaction in a model
      system of d-glucose and glycine.
AB  - A kinetic model for a high-intensity ultrasound-assisted Maillard reaction model
      system of d-glucose and glycine was proposed; activation energy (Ea) for each
      reaction step was calculated. Results showed that the generation of dicarbonyl
      compounds was significantly promoted by high-intensity ultrasound (e.g. Ea values
      for 1-deoxyglucosone were 60.9 +/- 9.7 kJ mol-1 and 105.5 +/- 9.9 kJ mol-1 in
      ultrasonic and thermal Maillard reaction, respectively), which resulted in a
      significantly higher concentration of colored and volatile Maillard reaction
      products generated in ultrasound-assisted Maillard reaction compared with that in
      thermal Maillard reaction. However, as a competitive reaction, the isomerization
      of d-glucose was suppressed and required significantly higher Ea values in
      ultrasound-assisted Maillard reaction (100.8 +/- 6.2 kJ mol-1) compared with that
      in thermal Maillard reaction (84.2 +/- 5.7 kJ mol-1). These finding may be
      attributed to an extremely high temperature and pressure environment, despite of
      being only momentarily, generated by high-intensity ultrasound.

PMID- 30100482
TI  - Purification and characterization of an intracellular alpha-l-rhamnosidase from a
      newly isolated strain, Alternaria alternata SK37.001.
AB  - A strain, Alternaria alternata SK37.001, which produces an intracellular alpha-l
      rhamnosidase, was newly isolated from citrus orchard soil. The molecular mass of
      the enzyme was 66 kDa, as evaluated by SDS-PAGE and 135 kDa, as determined by gel
      filtration, which indicated that the enzyme is a dimer. The enzyme had a specific
      activity of 21.7 U mg-1 after step-by-step purification. The optimal pH and
      temperature were 5.5 and 60  degrees C, respectively. The enzyme was relatively
      stable at a pH of 4.0-8.0 and a temperature between 30 and 50  degrees C compared
      with other pH levels and temperatures investigated. The enzyme activity was
      accelerated by Ba2+ and Al3+ but inhibited by Ni2+, Cu2+ and Co2+, especially
      Ni2+. The kinetic parameters of Km and Vmax were 4.84 mM and 53.1 MUmol mg-1 min
      1, respectively. The alpha-l-rhamnosidase could hydrolyze quercitrin, naringin
      and neohesperidin, hesperidin and rutin rhamnose-containing glycosides but could
      not hydrolyze ginsenoside Rg2 or saiko-saponin C.

PMID- 30100483
TI  - Rapid autographic method for detection of enzymatic browning inhibitors based on
      enzyme immobilization.
AB  - This work describes a TLC-coupled bioautographic assay suitable for the
      separation and detection of apple polyphenol oxidase (PPO) inhibitors from
      natural extracts. PPO was immobilised in agar containing l-DOPA as substrate and
      3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) to enhance colour
      development. The inhibition was detected as white spots on reddish background.
      Minimum amount of PPO inhibitors detected was 0.0125 ug of 4-hexylresorcinol,
      0.025 ug of ascorbic acid, 0.5 ug of cysteine and 1 ug of kojic acid. The assay
      was compatible with normal and reverse phase TLC systems and allows detecting
      compounds that directly had action on the enzyme as well as agents that could
      convert quinones back to their reduced form. The chromatographic run evidenced
      the different nature of enzymatic browning inhibitory compounds from garlic and
      onion extracts. Using natural enzymes will provide a fast and cheap alternative
      for target specific exploration of natural enzymatic inhibitors.

PMID- 30100485
TI  - Novel low-abundance allergens from mango via combinatorial peptide libraries
      treatment: A proteomics study.
AB  - Mango allergy is a rare condition, which may cause severe hypersensitivity
      reactions, such as anaphylaxis, angioedema, asthma and contact dermatitis. By
      exploiting the combinatorial peptide ligand library (CPLL) technology, mango
      proteomes have been extracted and the presence of traces of allergens assessed
      via Western blot analysis two-dimensional maps. Upon reactive spot elution and
      mass spectrometry analyses, four major mango allergens could be identified for
      the first time and shown to be in common with three of the five known banana
      species. These allergens include: Mus a 1, Mus a 2 and Mus a 5. Additional mango
      allergens detected do not seem to be in common with the banana species. In
      particular, a pectinesterase and a superoxide dismutase, both widely described as
      allergens, could be identified in mango extracts. Conversely, plain mango
      extracts not treated with CPLLs did not exhibit any reactive spots in Western
      blot analysis.

PMID- 30100484
TI  - Phomopsis longanae-induced pericarp browning and disease development of longan
      fruit can be alleviated or aggravated by regulation of ATP-mediated membrane
      lipid metabolism.
AB  - Compared to P. longanae-inoculated longan fruit, DNP-treated P. longanae
      inoculated longans displayed higher fruit disease index, pericarp browning index
      and cell membrane permeability. Moreover, they exhibited higher activities of
      phospholipase D, lipase and lipoxygenase, lower amounts of phosphatidylcholine,
      phosphatidylinositol and USFA (unsaturated fatty acids) as well as higher amounts
      of phosphatidic acid and SFA (saturated fatty acids). Additionally, lower ratio
      of USFA to SFA and USFA index were shown in DNP-treated P. longanae-inoculated
      longans. However, ATP-treated P. longanae-inoculated longans exhibited the
      opposite results. These findings indicated that DNP stimulated longan pericarp
      browning and disease development caused by P. longanae resulted from the
      increases in activities of membrane lipids-degrading enzymes, promoting
      degradation of membrane phospholipids and USFA, and disruption of membrane
      structural integrity. Whereas, the opposite results observed in ATP-treated P.
      longanae-inoculated longans were due to the reduction in activities of membrane
      lipids-degrading enzymes and the maintenance of membrane structural integrity.

PMID- 30100487
TI  - Morphology evolution and gelation mechanism of alkali induced konjac glucomannan
      hydrogel.
AB  - A molecular-level mechanism of alkali induced konjac glucomannan (KGM) hydrogel
      gelation processing is considered with the application of nuclear magnetic
      resonance (NMR) spectroscopy and atomic force microscopy (AFM) as complementary
      methods to diffusive wave spectroscopy (DWS) microrheology and thermoanalysis. It
      is shown that deacetylation of KGM chains occurs immediately upon mixing with
      Na2CO3, inducing self-packaging. Partial unfolding of the packed loose structure
      of dehydrated KGM is observed upon heating. The configuration transition from
      random coils to self-assembling filament networks takes place before KGM
      aggregating to form large irreversible bundles with a lower degree of cross
      linking. The gelation is not fulfilled until the temperature is increased to
      above 70  degrees C when the significant agglomeration is initiated among
      transitional fibrils to form junction zones essentially composed of acetyl-free
      portions. This suggests the intermolecular aggregation of KGM chains not simply
      regarding to hydrogen bonds, but essentially relating to hydrophobic
      interactions.

PMID- 30100486
TI  - New insights in the composition of wax and sterol esters in common and mutant
      sunflower oils revealed by ESI-MS/MS.
AB  - Wax esters (WEs) and steryl esters (SEs) are minor components of sunflower oils
      formed by the esterification of long chain fatty alcohols and sterols to fatty
      acids. These compounds have similar carbon numbers and polarities making them
      difficult to separate using conventional chromatographic methods. In this study,
      electrospray ionisation-tandem mass spectrometry (ESI-MS/MS) allowed the rapid
      and accurate profiling of WEs and SEs acyl moieties in total ester fractions of
      common and mutant sunflower oils with different fatty acid profiles. The acyl
      composition of both WEs and SEs partially reflected that of the oil and the high
      oleic background displayed the lowest level of crystallisable waxes. ESI-MS/MS
      complemented by GC-MS analyses revealed that SEs contain 17-30% of previously
      unreported methylsterol moieties. We demonstrated that these compounds are
      overlooked by official sterol analytical methods which may have consequences for
      quality control and authentication of vegetable oils prior to commercialisation.

PMID- 30100488
TI  - A shotgun method for high throughput screening microcystins in Margarya
      melanioides on a triple quadrupole tandem mass spectrometry.
AB  - A selective and sensitive procedure for determining seven hazardous microcystins
      in Margarya melanioides, using tandem mass spectrometry, is presented. The
      product ion m/z 135.2 was selected as representative for precursor ion scanning
      and used to increase overall sensitivity of this shotgun method. The method was
      validated, and recoveries ranged from 69.3 to 87.9%, with the relative standard
      deviation less than 10%. Limits of detection and quantitation were less than 3.1
      and 9.3 ng.mL-1, respectively. A total of 60 samples were tested using this
      method. 38 samples were found to be contaminated with microcystins, among which
      there are 31 samples whose estimated daily intake (EDI) was 0-7.8 times higher
      than the tolerable daily intake (TDI). This method would be useful for carrying
      out direct, ultra-rapid quantification of microcystins in foods, and is of
      significant interest for environmental and food safety applications.

PMID- 30100489
TI  - Biomass reinforced graphene oxide solid/liquid phase membrane extraction for the
      measurement of Pb(II) in food samples.
AB  - Here, a solid/liquid phase extraction mode was used for the preconcentration of
      Pb(II) in water and food samples through a biomass reinforced graphene oxide
      (BGO) membrane. Taking advantage of the two modes, the synergistic effect of BGO
      membrane (solid extraction) and organic solvent (liquid extraction) enhances the
      extraction efficiency toward target ion. In detail, the effect of composition
      parameters in BGO membrane and experiment conditions such as pH, eluent types,
      elution time and sample volume were optimized, as well as shows no obvious
      interference toward different competing ions. Under the optimal experiment
      conditions, the limit of detection, precision as RSD% of this method were found
      to be 0.84 MUg L-1 and 4.65%, respectively. Moreover, the large enrichment factor
      of BGO membrane demonstrates the applicability of the use of large sample
      volumes. Furthermore, the method was successfully verified by analyzing spiked
      Pb(II) in water and food samples.

PMID- 30100490
TI  - Comparative analysis of phytochemicals and activity of endogenous enzymes
      associated with their stability, bioavailability and food quality in five
      Brassicaceae sprouts.
AB  - Five Brassicaceae sprouts (white cabbage, kale, broccoli, Chinese cabbage,
      arugula) were comparatively analyzed based on phytochemicals (polyphenols,
      glucosinolates, carotenoids, chlorophylls, ascorbic acid) content and
      accompanying enzymes associated with phytochemical stability and bioavailability
      (peroxidases, myrosinase, and polyphenol-oxidase) that consequently impact food
      quality. Significantly high content of polyphenols and glucosinolates, as well as
      a high antioxidant activity were found in white cabbage, followed by kale
      sprouts. In addition, white cabbage contained higher amount of fibers and lower
      polyphenol-oxidase activity which potentially indicates prevention of browning
      and consequently better sprout quality. Arugula and broccoli showed higher
      activity of myrosinase that may result in higher bioavailability of active
      glucosinolates forms. According to our data, sprouts are cheap, easy- and fast
      growing source of phytochemicals but also they are characterized by different
      endogenous enzymes activity. Consequently, this parameter should also be taken
      into consideration in the studies related to the health benefits of the plant
      based food.

PMID- 30100491
TI  - More data on the Ross procedure.

PMID- 30100492
TI  - "Words are the source of misunderstandings"-Antoine de Saint-Exupery, Le Petit
      Prince (1943).

PMID- 30100493
TI  - Radial artery advocacy.

PMID- 30100494
TI  - In memoriam Hugh H. McAllister, Jr., M.D.

PMID- 30100495
TI  - Adaptations of hepatic lipid metabolism and mitochondria in dairy cows with mild
      fatty liver.
AB  - The inevitable deficiency in nutrients and energy at the onset of lactation
      requires an optimal adaptation of the hepatic metabolism to overcome metabolic
      stress. Fatty liver is one of the main health disorders after parturition.
      Therefore, to investigate changes in hepatic lipid metabolic status and
      mitochondria in dairy cows with mild fatty liver, liver and blood samples were
      collected from healthy cows (n = 15) and cows with mild fatty liver (n = 15). To
      determine the effects of palmitic acids (PA), one of the major component of fatty
      acids, on lipid metabolism and mitochondria in vitro, calf hepatocytes were
      isolated from healthy calves and treated with various concentrations of PA (0,
      50, 100, and 200 MUM). Dairy cows with mild fatty liver displayed hepatic lipid
      accumulation. The protein levels of sterol regulatory element-binding protein 1c
      (SREBP-1c) and peroxisome proliferator-activated receptor-alpha (PPARalpha) and
      mRNA levels of acetyl CoA carboxylase 1 (ACC1), fatty acid synthase (FAS), acyl
      CoA oxidase (ACO), and carnitine palmitoyltransferase 1A (CPT1A) were
      significantly higher in dairy cows with mild fatty liver than in control cows.
      The hepatic mitochondrial DNA content, mRNA levels of oxidative phosphorylation
      complexes I to V (CO 1-V), protein levels of cytochrome c oxidase subunit IV (COX
      IV), voltage dependent anion channel 1 (VDAC1), peroxisome proliferator activated
      receptor-gamma coactivator-1alpha (PGC-1alpha) and nuclear respiratory factor 1
      (NRF1), and adenosine triphosphate (ATP) content were all markedly increased in
      the liver of dairy cows with mild fatty liver compared with healthy cows. The PA
      treatment significantly increased lipid accumulation; protein levels of SREBP-1c
      and PPARalpha; and mRNA levels of ACC1, FAS, ACO, and CPT1A in calf hepatocytes.
      Moreover, the mitochondrial DNA content, mRNA levels of CO 1-V, protein levels of
      COX IV, VDAC1, PGC-1alpha, NRF1, mitochondrial transcription factor A, and ATP
      content were significantly increased in PA-treated hepatocytes compared with
      control hepatocytes. The protein level of mitofusin-2 was significantly decreased
      in PA-treated groups. In conclusion, lipid synthesis and oxidation, number of
      mitochondria, and ATP production were increased in the liver of dairy cows with
      mild fatty liver and PA-treated calf hepatocytes. These changes in hepatic
      mitochondria and lipid metabolism may be the adaptive mechanism of dairy cows
      with mild fatty liver.

PMID- 30100496
TI  - Short communication: Effect of dietary phosphorus deprivation in late gestation
      and early lactation on the calcium homeostasis of periparturient dairy cows.
AB  - Environmental concerns with P of animal origin polluting surface waters are
      leading to legal incentives aimed at reducing the dietary P content of dairy cow
      rations to the lowest possible level that does not negatively affect health and
      productivity. The objective of the present study was to determine the effect of
      feeding rations with low dietary P content in late gestation on the Ca
      homeostasis of the periparturient dairy cow. Eighteen multiparous dairy cows were
      either fed a P-deficient (0.15% P in dry matter antepartum and 0.20% P in dry
      matter postpartum) but otherwise balanced ration or a control ration with
      adequate P content (0.28% P in dry matter antepartum and 0.44% P in dry matter
      postpartum) during the last 4 wk of gestation until d 10 postpartum. Blood was
      obtained before initiation of P-deprivation (baseline) and -10, -2, +1, +3, and
      +10 d relative to parturition to be analyzed for plasma concentrations of Ca [Ca]
      and inorganic phosphate [Pi]. In addition, plasma concentrations of parathyroid
      hormone [PTH], the bone resorption marker CrossLaps [CTX], 25-hydroxyvitamin D,
      and 1,25-dihydroxyvitamin D were determined in a subset of samples. Feeding a P
      deficient diet for 4 wk antepartum positively affected the Ca homeostasis of
      periparturient cows. Clinical hypocalcemia occurred in 3/9 control and 0/9 P
      deprived cows. [Calcium], [PTH], and plasma concentrations of vitamin D
      metabolites did not differ between groups until parturition, whereas [Pi] was
      decreased and [CTX] significantly increased in P-deprived animals. At parturition
      [PTH] was significantly greater in control cows compared with P-depleted cows.
      The P-deprived cows had significantly higher [Ca] than control cows on d +1 (2.46
      +/- 0.11 vs. 2.27 +/- 0.41 mmol/L) and +2 (2.61 +/- 0.13 vs. 2.35 +/- 0.25
      mmol/L). Plasma [CTX] was significantly higher in P-deprived than in control cows
      on d +2. Bone resorption and the typical increase in 1,25-dihydroxyvitamin D in
      periparturient P-deprived cows seemed to occur despite the smaller rise of [PTH],
      suggesting either greatly increased sensitivity to PTH or bone mobilization
      independent of PTH. Future studies must explore potentially negative effects of P
      deprivation antepartum on health and productivity of the dairy cow in the
      following lactation.

PMID- 30100497
TI  - Effect of partial whey protein depletion during membrane filtration on thermal
      stability of milk concentrates.
AB  - Membrane filtration technologies are widespread unit operations in the dairy
      industry, often employed to obtain ingredients with tailored processing
      functionalities. The objective of this work was to better understand the effect
      of partial removal of whey proteins by microfiltration (MF) on the heat stability
      of the fresh concentrates. The micellar casein concentrates were compared with
      control concentrates obtained using ultrafiltration (UF). Pasteurized milk was
      microfiltered (80 kDa polysulfone membrane) or ultrafiltered (30 kDa cellulose
      membrane) without diafiltration (i.e., no addition of water) to 2* and 4*
      concentration, based on volume reduction. The final concentrates showed no
      differences in pH, casein micelle size, or mineral concentration in the serum
      phase. The micellar casein retentates (obtained by MF) showed a 20 and 40%
      decrease in whey protein concentration compared with the corresponding UF milk
      protein concentrates for 2* and 4* concentration, respectively. The heat
      coagulation time decreased with increasing protein concentration, regardless of
      the treatment; however, MF retentates showed a higher thermal stability than the
      corresponding UF controls. The average diameter for casein micelles increased
      after heating in UF but not MF concentrates. The turbidity (measured by light
      scattering) increased after heating, but to a higher extent for UF retentates
      than for MF retentates at the same protein concentration. It was concluded that
      the reduced amount of whey protein in the MF retentates caused a significant
      increase in the heat stability compared with the corresponding UF retentates.
      This difference was not due to ionic composition differences or pH, but to the
      type and amount of complexes formed in the serum phase.

PMID- 30100498
TI  - Therapeutic effects of kefir grain Lactobacillus-derived extracellular vesicles
      in mice with 2,4,6-trinitrobenzene sulfonic acid-induced inflammatory bowel
      disease.
AB  - Kefir is a fermented product from yeast and lactic acid bacteria, and has been
      associated with various health benefits including relieving inflammatory bowel
      disease. Recently, it has been shown that gram-positive bacteria produce
      extracellular vesicles (EV). The EV could be appearing as potentially important
      mediators of cell to cell interaction. In this study, we explored the role of
      kefir grain Lactobacillus-derived EV in modulating inflammation responses via
      alleviating the production of inflammatory cytokines in tumor necrosis factor
      alpha (TNF-alpha)-induced inflammation in Caco-2 cells and the 2,4,6
      trinitrobenzene sulfonic acid-induced inflammatory bowel disease mouse model.
      Kefir-derived Lactobacillus EV were isolated by ultracentrifugation of the
      culture medium of 3 different kefir-derived strains (i.e., Lactobacillus kefir,
      Lactobacillus kefiranofaciens, and Lactobacillus kefirgranum). Nanoparticle
      tracking analysis showed that the size of isolated kefir-derived Lactobacillus EV
      was within 80 to 400 nm, and kefir-derived Lactobacillus EV uptake into recipient
      Caco-2 cells was confirmed by fluorescence labeling. Treatment of each kefir
      derived Lactobacillus EV onto TNF-alpha-stimulated Caco-2 cells significantly
      reduced the level of both mRNA expression and secretion of IL-8, and Western blot
      analysis revealed that such an effect was related to inhibition of TNF-alpha
      signaling mediated by reducing the phosphorylation of p65, a subunit of NF-kB.
      Subsequent administration of kefir-derived Lactobacillus EV into inflammatory
      bowel disease-induced mice significantly alleviated the body weight loss and
      rectal bleeding, and enhanced stool consistency. Histological examination showed
      that kefir-derived Lactobacillus EV substantially reduced the infiltration of
      transmural leukocytes and loss of goblet cells within the colon, and the serum
      level of myeloperoxidase was significantly lower in the EV-treated group than
      control group. Our study demonstrates that kefir-derived Lactobacillus EV can be
      potentially used for developing innovative strategies for alleviating
      inflammatory bowel disease.

PMID- 30100499
TI  - Short communication: Associations of udder edema with health, milk yield, and
      reproduction in dairy cows in early lactation.
AB  - Udder edema (UE) is a common condition of cows around calving, but its effects
      are not well characterized. The objectives of this study were to determine the
      associations of UE with the incidence of health disorders and with milk yield and
      reproduction in dairy cows in early lactation. On 3 commercial farms, UE was
      scored weekly on 1,346 cows, on a scale of 0 to 3, from 1 wk before calving to 3
      wk after calving. Among cows with complete UE scores, 30% never had edema, 12%
      had edema only prepartum, 11% had it only postpartum, and 48% had edema prepartum
      and in at least 1 wk postpartum. Udder edema was associated with a greater
      incidence of clinical mastitis before 30 d in milk (5 vs. 2%). Subclinical
      ketosis (blood beta-hydroxybutyrate >=1.2 mmol/L) was more prevalent at wk 2 (11
      vs. 6%) postpartum among cows with UE. No association was observed of UE with
      other diseases or culling in early lactation. In a subset of 912 cows with
      complete UE and 3 test-days of milk yield data, differences were observed in
      yield at test d 1 among UE categories. Cows with UE only prepartum produced less
      milk (39.9 kg/d) than cows with UE postpartum only (42.4 kg/d) and cows with UE
      both prepartum and postpartum (41.6 kg/d), none of which differed from cows
      without UE (40.9 kg/d). Udder edema was not associated with the prevalence of
      anovulation, or the time to or probability of pregnancy at first insemination,
      yet to 300 d in milk, cows that had UE postpartum had a shorter time from calving
      to pregnancy than cows without UE. The associations of UE with health and
      productivity are mixed, and the mechanisms underlying UE and its effects merit
      further investigation.

PMID- 30100501
TI  - Dose frequency of prostaglandin F2alpha administration to dairy cows exposed to
      presynchronization and either 5- or 7-day Ovsynch program durations: Ovulatory
      and luteolytic risks.
AB  - We hypothesized (1) that neither duration of the Ovsynch program nor dose
      frequency of PGF2alpha would change the proportion of cows with complete
      luteolysis (progesterone <0.4 ng/mL 72 h after PGF2alpha) and (2) that the
      additional GnRH treatment administered as part of a presynchronization program
      would not alter the proportion of anovulatory cows starting the timed artificial
      insemination (AI) program compared with an alternative shorter presynch program
      including only 1 GnRH treatment. Lactating Holstein cows (n = 406) were milked 3
      times daily and enrolled in a 2 * 2 * 2 factorial experiment consisting of 8
      treatments before the first postpartum AI. Treatments were used to test
      ovulatory, luteal, and luteolytic outcomes to 3 main effects: (1) 2 GnRH
      PGF2alpha presynchronization programs (PG-3-G vs. Double Ovsynch), (2) 2 Ovsynch
      program durations [5 d: GnRH (GnRH-1)-5 d-PGF2alpha-24 h-PGF2alpha-32 h-GnRH
      (GnRH-2)-16 h-timed AI; 7 d: GnRH-1-7 d-PGF2alpha-56 h-GnRH-2-16 h-timed AI], and
      (3) 2 PGF2alpha dose frequency treatments (2 * 25 mg) 24 h apart versus 1 dose (1
      * 50 mg) of PGF2alpha administered 72 h before timed AI. The presynchronization
      treatments of PG-3-G and Double Ovsynch had no effect on the proportion of cows
      with luteal function at the onset of the Ovsynch treatments (87.9 vs. 86.2%).
      Although ovulatory responses were similar after GnRH-1 (>60%), Double Ovsynch
      cows tended to have greater ovulatory responses than PG-3-G after GnRH-2 (95.3
      vs. 90.6%). The 2 * 25-mg doses of PGF2alpha and the 1 * 50-mg dose induced
      luteolysis in both Ovsynch treatment durations, but the 1 * 50-mg dose was less
      effective in the 5-d program. More pregnancy per AI (P/AI; 49.2%) tended to occur
      in the PG-3-G cows in the 7-d program compared with the other treatment
      combinations (range: 32.4-37.4%; Ovsynch * presynch interaction). In addition, an
      Ovsynch * PGF2alpha dose frequency interaction resulted in cows receiving the 1 *
      50-mg dose in the 7-d program having the greatest P/AI (46.1%) and cows receiving
      the 1 * 50-mg dose in the 5-d program having the least P/AI (30.6%). We conclude
      that complete luteolysis was less effective in the 5-d program when the 1 * 50-mg
      dose was applied, but both PGF2alpha dose frequencies (1 * 50 mg and 2 * 25 mg 24
      h apart) effectively induced complete luteolysis in the 7-d program. Treatments
      producing complete luteolysis tended to be related to subsequent pregnancy
      outcomes.

PMID- 30100500
TI  - Does the dry cow treatment with monensin controlled release capsule affect
      Parmigiano Reggiano cheese production?
AB  - We investigated the effects of monensin controlled-release capsule (CRC;
      Kexxtone, Eli Lilly and Company Ltd., Indianapolis, IN) preventative ketosis
      treatment on the traditional cheesemaking process as well as the final
      characteristics of Parmigiano Reggiano (PR) cheese. The use of this prevention
      product to reduce the incidence of ketosis in transition dairy cows was approved
      by the European Medicines Agency in 2013. No previous studies are available
      concerning the effects of this treatment on prolonged-ripening cheese production
      such as PR. In PR cheese production, feed, feed additives, and cow treatments are
      strictly regulated to avoid any possible interference with traditional
      manufacturing processes. For these reasons, on 1 farm where all milk was used for
      PR cheese production, monensin CRC was administered to 33 cows, 21 d before
      calving in the monensin-treated group (TRT), whereas untreated cows with similar
      breed and parity characteristics constituted the control group (CTR). For 20 wk,
      milk obtained from each group and whey starter were separately managed and
      transported in the cheese factory, where 2 cheese wheels per group were produced
      daily, making 552 PR cheese wheels in total. Morning bulk tank milk composition,
      cheesemaking properties, and whey starter fermentation activities were analyzed
      twice a week. Every aspect of the cheesemaking process was recorded and the
      resulting cheese was evaluated after 36 h and 6, 12, and 18 mo from production
      for yield, texture defects, composition, and fatty acids profile. Milk from the 2
      groups differed for somatic cell content (TRT = 3.04 vs. CTR = 4.06, somatic cell
      score), total bacterial count (TRT = 4.08 vs. CTR = 6.08 * 1,000 cfu/mL),
      titratable acidity (TRT = 3.66 vs. CTR = 3.72 Soxhlet-Henkel degrees/50 mL), and
      casein content percentage (TRT = 2.4 vs. CTR = 2.5%). Whey starter parameters
      were comparable between the 2 groups. Final cheese composition and organoleptic
      profile were not influenced by the treatment, except for C18:1 content being
      enhanced (TRT = 22.8 vs. CTR = 20.8% of fatty acids). Percentage of defected
      ripened cheese was significantly lower in the treated group, both at x-ray
      evaluation performed at 6 mo (TRT = 6.2 vs. CTR = 12.3%) and at the consortium
      inspection, performed at 12 mo of ripening (TRT = 1.5 vs. CTR = 6.5%). On the
      other hand, average cheese yield at 18 mo of ripening was partially reduced (TRT
      = 7.5 vs. CTR = 7.7%). Overall, the use of monensin CRC had no negative effect on
      the cheesemaking process, prolonged ripening cheese characteristics, milk
      composition, or whey starter quality.

PMID- 30100502
TI  - Lateral flow immunoassay integrated with competitive and sandwich models for the
      detection of aflatoxin M1 and Escherichia coli O157:H7 in milk.
AB  - Pathogens, mycotoxins, or antibiotics may exist in a food sample. Micro- and
      macromolecular substances must be detected quickly. A rapid and convenient
      lateral flow immunoassay (LFI) integrated with competitive and sandwich models
      was developed to detect micro- and macromolecular substances. In this study,
      aflatoxin M1 (AFM1) and Escherichia coli O157:H7 were selected as the micro- and
      macromolecular substances, respectively. Two test lines in the LFI test strip
      were evaluated to detect AFM1 and E. coli O157:H7 by competitive and sandwich
      models. Results showed that the limits of detection for detecting AFM1 and E.
      coli O157:H7 were 50 pg.mL-1 and 1.58 * 104 cfu.mL-1, respectively. The whole
      assay time was 30 min. The recoveries of gold nanoparticle-LFI ranged from 78.0
      to 111.6% with coefficients of variation in the range of 3.9 to 8.5% for the
      detection of AFM1. For the detection of E. coli O157:H7, the range of recoveries
      was from 70.1 to 89.6% with coefficients of variation ranging from 4.9 to 13.0%.
      This study not only tested sensitivity and specificity, but also was a systematic
      study of location of 2 test lines of the LFI test strip integrated with
      competitive and sandwich models.

PMID- 30100503
TI  - Detection of quantitative trait loci and putative causal variants affecting
      somatic cell score in dairy sheep by using a 50K SNP chip and whole-genome
      sequencing.
AB  - This study presents a scan of the ovine genome to identify quantitative trait
      loci (QTL) influencing the somatic cell score (SCS), a classical indicator of
      subclinical mastitis in sheep, and a subsequent high-resolution analysis of one
      of the identified QTL regions based on the analysis of whole-genome sequence data
      sets. A half-sib commercial population of Churra sheep genotyped with a 50K SNP
      chip was analyzed using linkage analysis (LA) and combined linkage and linkage
      disequilibrium analysis (LDLA). By LA, 2 5% chromosome-wide significant QTL on
      OAR5 and OAR25 and one 5% genome-wide significant QTL on ovine chromosome 20
      (OAR20) were detected, whereas 22 significant associations were identified by
      LDLA. Two of the associations detected by LDLA replicated LA-detected effects
      (OAR20, OAR25). We compared the detected associations with previously reported
      QTL in sheep and cattle, and functional candidate genes were identified within
      the estimated confidence intervals. We then performed a high-resolution analysis
      of the OAR20 QTL region, the most significant QTL region identified by LA that
      replicated a QTL previously described in Churra sheep for SCS using
      microsatellite markers. For that, 2 segregating trios of 2 segregating families
      for the OAR20 QTL (each including the Qq sire and 2 daughters, QQ and qq) were
      selected for whole-genome sequencing. The bioinformatic analysis of the 6
      sequenced samples performed across the genomic interval considered (14.2-41.7 Mb)
      identified a total of 227,030 variants commonly identified by 2 independent
      software packages. For the 3 different concordance tests considered, due to
      discrepancies regarding the QTL peak in the segregating families, the list of
      mutations concordant with the QTL segregating pattern was processed to identify
      the variants identified in immune-related genes that show a moderate/high impact
      on the encoded protein function. Among a list of 85 missense variants concordant
      with the QTL segregation pattern that were within candidate immune-related genes,
      13 variants distributed across 7 genes [PKHD1, NOTCH4, AGER, ENSOARG00000009395
      (HLA-C, Homo sapiens), ENSOARG00000015002 (HLA-B, H. sapiens), MOG, and
      ENSOARG00000018075 (BoLA, Bos taurus, orthologous to human HLA-A] were predicted
      to cause deleterious effects on protein function. Future studies should assess
      the possible associations of the candidate variants identified herein in
      commercial populations with indicator traits of udder inflammation (SCS, clinical
      mastitis).

PMID- 30100504
TI  - Faba bean (Vicia faba) inclusion in dairy cow diets: Effect on nutrient
      digestion, rumen fermentation, nitrogen utilization, methane production, and milk
      performance.
AB  - The objective of this study was to determine the effect of replacing on
      isonitrogenous and isoenergetic basis soybean meal (SBM) and corn grain with
      ground or rolled faba bean (FB; Vicia faba major var. Baie-Saint-Paul) in dairy
      cow diets (17% of diet dry matter) on nutrient digestion, rumen fermentation, N
      utilization, methane production, and milk performance. For this purpose, 9
      lactating cows were used in a replicated 3 * 3 Latin square design (35-d period)
      and fed (ad libitum) a total mixed ration (forage:concentrate ratio = 59:41 on a
      dry matter basis). In the concentrate portion, SBM and corn grain (control diet)
      were completely and partially replaced, respectively, with either ground or
      rolled FB. Ruminal degradability (in sacco) of crude protein was higher for
      ground FB (79.4%) compared with SBM (53.3%) and rolled FB (53.2%). Including FB
      in the diet did not affect dry matter intake, milk production, and milk
      composition. Experimental treatment had no effect on total volatile fatty acid
      concentration, acetate-to-propionate ratio, and protozoa numbers. Compared with
      cows fed the control diet, ruminal NH3 concentration increased and tended to
      increase for cows fed ground FB and rolled FB, respectively; however, we found no
      difference in ruminal NH3 concentration between the 2 processed FB. Apparent
      total-tract digestibility of crude protein was similar between cows fed the
      control diet and cows fed rolled FB and tended to increase for cows fed ground FB
      compared with cows fed the control diet. Feeding rolled FB decreased CP
      digestibility compared with feeding ground FB. Urinary and manure (feces + urine)
      N excretion (g/d or as a proportion of N intake) were not affected by the
      inclusion of FB in the diet. Enteric CH4 production was similar among the
      experimental diets. Results from this study show that including FB (17% of
      dietary dry matter) at the expense of SBM and corn grain in the diet had no
      effect on milk production, N excretion, and enteric CH4 production of dairy cows.

PMID- 30100505
TI  - Growth performance and health of dairy calves given water treated with a reverse
      osmosis system compared with municipal city water.
AB  - Our objective was to determine effects of drinking reverse osmosis water (RW)
      versus municipal city water (MW) on growth, nutrient utilization, and health
      scores of calves. Twenty-four Holstein calves (14 females, 10 males; 2 d old;
      44.6 +/- 6.10 kg of body weight), housed in individual hutches, were used in a 10
      wk randomized complete block design study. Calves were blocked by birthdate and
      sex. Treatments were RW (Culligan Water Filtration System, Brookings, SD) versus
      MW (Brookings Municipal Utilities, Brookings, SD) that contained 13 and 387 mg/L
      of total dissolved solids, respectively. Milk replacer (28% crude protein; 18%
      fat) was fed twice daily during wk 1 through 5 and then once daily during wk 6.
      At each feeding, 0.45 kg of dry milk replacer was mixed with 2.83 L of the
      respective water type according to treatment. Calves were fed water, respective
      to treatment, and calf starter pellets ad libitum throughout the study. All
      intakes were recorded daily. Daily total respiratory scores (healthy <=3, sick
      >=5) were calculated from the sum of scores for rectal temperature, cough, and
      ocular and nasal discharges. Fecal consistency scores (0 = firm, 3 = watery) were
      also recorded daily. Body weights and frame growth were measured 2 d every 2 wk
      and jugular blood samples were collected 1 d every 2 wk at 3 h after the morning
      feeding. Fecal grab samples were collected 5 times per day for 3 d during wk 10
      for analysis of apparent total-tract digestibility of nutrients. We found
      treatment by week interactions for dry matter intake and gain-to-feed ratio, and
      total dry matter intake increased more during the study for RW than MW. Gain-to
      feed ratio was greater during the first few weeks of the feeding period for RW
      compared with MW and then comparable during the rest of study. Water intake was
      less in RW than MW, potentially indicating more efficient water use by calves.
      Frame growth, body weight, average daily gain, serum glucose, plasma urea
      nitrogen, beta-hydroxybutyrate, total-tract digestibility of dry matter, and
      crude protein were similar. Fecal scores tended to be lower (firmer) in calves on
      RW, with an interaction by time. Respiratory scores decreased during the weaning
      period when calves drank RW. Results demonstrated calves drinking RW had similar
      growth and improved health scores with treatment by time interactions compared
      with MW.

PMID- 30100507
TI  - Typeability of MALDI-TOF assay for identification of non-aureus staphylococci
      associated with bovine intramammary infections and teat apex colonization.
AB  - Matrix-assisted laser desorption/ionization time of flight (MALDI-TOF), a culture
      dependent assay, has recently been implemented for routine identification of non
      aureus staphylococci (NAS) species from milk, but the assay has never been
      investigated for NAS from nonmilk or environmental samples. The objective of this
      study was to evaluate the typeability of the MALDI-TOF assay for the
      identification and differentiation of bovine-associated NAS species on
      aseptically collected quarter milk and teat skin samples in dairy herds. In 8
      herds, 14 to 20 cows with elevated somatic cell count were randomly selected for
      teat skin swabs and foremilk samples from right hind and left front quarters.
      Teat skin swabs and milk samples were collected aseptically for preliminary
      identification using bacterial culture on chromogenic and calf blood agars.
      Colonies from milk and teat skin samples with suspicion of having NAS were
      identified to species-level by MALDI-TOF assay. Out of 511 isolates from 284
      quarters (142 cows), 78% (n = 399) were identified by MALDI-TOF. The percentage
      of correctly identified NAS from milk (91%, 105/115) using MALDI-TOF was higher
      than the percentage from teat skin (68%, 268/396). Out of the identified
      isolates, 93% (n = 373) were successfully identified as NAS, whereas the
      remaining 26 (7%) were shown to be other bacterial species. Out of 26 NAS
      isolates, 1 originated from milk (Corynebacterium stationis), whereas 25
      originated from teat skin representing Aerococcus viridans (n = 7), Bacillus
      pumilus (n = 13), Enterococcus saccharolyticus (n = 1), Clostridium septicum (n =
      1), Corynebacterium stationis (n = 2), and Corynebacterium casei (n = 1). The
      MALDI-TOF identified 85 (98/115) and 62% (245/396) of the isolates in the first
      test. Isolates that were not identified to species-level at first test were
      subjected to a second test, and 47 (8/17) and 32% (48/151) from milk and teat
      skin, respectively, were identified. After 2 rounds of MALDI-TOF, 22% (n = 112)
      of the isolates were not identified, representing 103 from teat skin and 9 from
      milk. Eighteen isolates without identification by MALDI-TOF were successfully
      identified to species-level using sequencing, where 16 were correctly identified
      as NAS, whereas the other 2 were Corynebacterium stationis. In conclusion, MALDI
      TOF is a reliable assay for identification and typeability of NAS species from
      aseptically collected quarter milk samples. The assay may be used for
      identification of NAS species from teat skin swabs. However, confirmation using
      nucleic acid-based tools is vital for accurate species identification of some
      species and strains.

PMID- 30100506
TI  - Antimicrobial resistance in bacteria isolated from mastitis in dairy cattle in
      France, 2006-2016.
AB  - In dairy cattle, mastitis is the most frequent bacterial disease, and the routine
      use of antibiotics for treatment and prevention can drive antimicrobial
      resistance (AMR). The aim of our study was to estimate the levels of AMR of the 3
      main bacteria isolated from dairy cattle with mastitis in France (Streptococcus
      uberis, Escherichia coli, and coagulase-positive staphylococci) and to
      investigate their changes over time. Data collected between 2006 and 2016 by the
      French surveillance network for AMR in pathogenic bacteria of animal origin
      (called RESAPATH) were analyzed. The proportions of mono- and multidrug
      resistance were calculated and the trends were investigated using nonlinear
      analyses applied to time series. Over the whole period, the lowest proportions of
      resistance in S. uberis isolates were observed for oxacillin (2.2%) and
      gentamicin (2.4%) and most resistance levels were below 20%. The trends in
      resistance showed some significant variation, mainly for S. uberis, but without a
      common pattern across the various antibiotics examined. For only 2 combinations
      of bacteria-antibiotic the trend in resistance showed a continuous increase from
      2006 to 2016: tetracycline resistance in S. uberis isolates and third-generation
      cephalosporin resistance in E. coli isolates. In E. coli, the highest proportions
      of resistance were observed for amoxicillin (28.1%) and tetracycline (23.1%).
      Resistance to third-generation cephalosporins in E. coli from dairy cattle was
      almost nil in 2006, but reached 2.4% in December 2016. This increase is
      particularly concerning because these antibiotics constitute one of the latest
      therapeutic alternatives to fight severe infectious diseases in humans. Except
      for penicillin (33.9%), the proportions of resistance in coagulase-positive
      staphylococci were below 11% during the whole study period. Multidrug resistance
      (isolates with acquired resistance to at least one antibiotic in 3 or more
      antibiotic classes) ranged from 2.4% for coagulase-positive staphylococci to 9.9%
      for S. uberis. These findings can serve as guidelines for practitioners in the
      choice of the most appropriate antibiotic according to the prevailing
      epidemiological context. Ultimately, our results contribute to risk assessment of
      AMR and provide a baseline for setting up and evaluating control measures and
      designing strategies to limit AMR.

PMID- 30100508
TI  - Short communication: Effect of washing method, grinding size, and the
      determination of an indigestible fraction on in situ degradation of starch in
      mature corn grain.
AB  - The objectives of this study were to determine (1) the effect of grinding size
      (1, 2, 4, and 6 mm) to determine effective ruminal disappearance (ERD); (2) the
      most adequate method to estimate the rapidly degradable fraction (A); (3) a time
      point to measure the indigestible fraction (C); and (4) the viability of using
      fewer time points to estimate starch fractional disappearance rate (kd) of mature
      corn grain. Fraction A was determined by rinsing in a bucket or washing machine,
      rumen immersion followed by bucket or washing machine, and water immersion for 30
      min followed by bucket or washing machine. Ruminal in situ incubations were
      performed at 48, 72, 96, and 120 h to determine fraction C, and at 0 (washing
      machine), 3, 6, 12, 18, 24, and 48 h to determine the kinetics of starch
      disappearance. Models were used with either 2 or 3 pools and kd was determined by
      the linear slope of the log-transformed bag residues as a proportion of incubated
      samples over time. The ERD was calculated as A + B [kd/(kd + kp)], where kp is
      the ruminal fractional passage rate = 16.0% h-1. Data were analyzed using PROC
      MIXED of SAS (SAS Institute Inc., Cary, NC) with the fixed effects of run (for
      fraction A analysis only) method (either washing or model), grinding size, and
      method by grinding size interaction, with cow as a random effect. Correlation
      between estimates calculated using all time points or combinations of 2 and 3
      time points were determined using PROC CORR. Fraction A was reduced as grinding
      size increased, but was not altered by washing method. Samples ground at 6 mm had
      greater fraction C than other grinding sizes at 48, 72, or 96 h, but not at 120
      h. Model affected the slowly degradable fraction (B) values solely, but the
      difference was minor (0.5 percentage units). Greater fractions B and C but
      reduced kd and ERD were observed as grinding size increased. Based on correlation
      analysis the 2-pool model, incubation times of 0, 3, and 48 h were suitable to
      evaluate ruminal starch degradation kinetics in mature corn. Ruminal in situ
      incubation at 120 h highlighted the lack of a fraction C of starch (0.13% of
      starch). Washing method did not affect determination of fraction A of starch.
      Ruminal in situ incubations of 0, 3, and 48 h for starch degradation kinetics
      using a 2-pool model were adequate for mature ground corn, but 120 h of
      incubation is suggested to confirm the existence or absence of a fraction C.
      Grinding size affected starch degradation kinetics and fraction A determination.

PMID- 30100509
TI  - Invited review: Roles of dietary n-3 fatty acids in performance, milk fat
      composition, and reproductive and immune systems in dairy cattle.
AB  - Mammals can synthesize all of the fatty acids (FA) necessary for proper health
      and functioning with the exception of FA in the n-3 (omega-3) and n-6 (omega-6)
      families of polyunsaturated fatty acids (PUFA), which should be supplied in the
      diet. The PUFA are the predominant type of lipid in dairy cattle diets; however,
      common feedstuffs are rich in n-6 FA, whereas the supply of n-3 FA in the
      intensive dairy industry is mainly limited to flaxseed and fish oils. The n-3 FA
      are involved in many biological systems and processes, and therefore their
      dietary supplementation is of special interest in dairy cattle. Furthermore,
      because milk, milk products, and meat are among the most important and widely
      used components in traditional and modern human diets, enrichment of these food
      products with n-3 FA is of special importance. The purpose of this review is to
      provide a comprehensive description of different aspects and outcomes involved in
      dietary n-3 FA supplementation in dairy cattle. I provide an inclusive review of
      the effects of n-3 FA on milk and milk solids and the FA profile in milk fat upon
      feeding a variety of flaxseed products or fish oil. Selective uptake of n-3 FA
      has been demonstrated in the ovary compartments, as well as in bull sperm and in
      the unborn calf through the placenta. Incorporation of these unique FA into the
      reproductive system influences many processes and exerts some positive effects on
      fertility. In addition, beneficial effects of feeding n-3 FA on the reproductive
      system of females and males can be achieved with supplementation of alpha
      linolenic acid from flaxseed or from eicosapentaenoic and docosahexaenoic acids
      from fish oil. This work provides a broad perspective and demonstrates the
      importance and potential of n-3 FA dietary supplementation in dairy cattle on the
      animal itself, as well as its secondary effects, which are associated with human
      nutrition and health.

PMID- 30100510
TI  - Identification and characterization of fluid milk consumer groups.
AB  - Consumption of fluid milk has steadily declined over the last few decades.
      Understanding the attributes of fluid milk products that are attractive to
      specific consumer groups may provide a sound basis for education and marketing to
      encourage increased dairy consumption and reverse the downward trend. The
      objective of this study was to identify the attributes of fluid milk that
      specific consumer groups find attractive and attributes that suggest a higher
      purchase likelihood. An adaptive choice-based conjoint (ACBC) survey was designed
      to assess attributes of fluid milk. The ACBC survey included Kano, importance,
      labeling identification, and beliefs questions to determine the key attributes
      that dictated consumer purchase and consumption. Self-reported purchase habits
      and attitudes for organic food products were also collected. Attributes in the
      ACBC exercise included fat content, package type, shelf life, and label claims.
      Maximum difference scaling was used to rank the importance of attributes in fluid
      milk that affected purchase. Maximum difference scaling was also used to rank
      qualities and issues associated with organic milk that were most motivating for
      those who identified as organic milk consumers. Results were analyzed by
      univariate and multivariate statistics. A total of 1,163 fluid milk consumers
      completed the survey, and of those, 434 were regular purchasers of organic milk.
      The ideal fluid milk from conjoint analysis was 2% milkfat, organic, packaged in
      a plastic jug, conventionally pasteurized, and contained no additives or label
      claims. The belief that "organic milk is healthier" was the most important
      motivator for purchases of organic milk, followed by the beliefs that "organic
      milk production encourages ethical treatment of animals" and "organic milk
      production supports local farms and farmers." Conjoint importance scores of all
      fluid milk consumers showed that milkfat content was the most important
      attribute, followed by flavor, package size, and price. For all milk consumers,
      designation as organic was ranked as the 8th most important of 14 attributes.
      Evaluation of these results on both aggregate and individual levels suggest that
      fluid milk consumers are not a homogeneous consumer group and that underlying
      consumer groups are led to purchase decisions by specific product features or
      expectations.

PMID- 30100511
TI  - Effect of rumen-protected B vitamins and choline supplementation on health,
      production, and reproduction in transition dairy cows.
AB  - The objectives were to determine the effects of a rumen-protected blend of B
      vitamins and choline (RPBC) on the incidence of health disorders, milk yield, and
      reproduction in early lactation and the effects on gene expression and liver fat
      infiltration. A randomized controlled trial in 3 commercial dairy herds (n =
      1,346 cows with group as the experimental unit; experiment 1) and a university
      research herd (n = 50 cows with cow as the experimental unit; experiment 2)
      evaluated the use of 100 g/cow per d of commercially available proprietary RPBC
      supplement (Transition VB, Jefo, St. Hyacinthe, Quebec, Canada), or a placebo,
      fed 3 wk before to 3 wk after calving. In experiment 2 liver biopsies were taken
      at 4 and 14 +/- 1 d in milk to measure triacylglycerol concentrations and
      expression of 28 genes selected to represent relevant aspects of liver
      metabolism. Treatment effects were assessed using multivariable mixed logistic
      regression models for binary health and reproductive outcomes; linear regression
      models for milk yield, dry matter intake, and liver outcomes; and survival
      analysis for time insemination and pregnancy. In experiment 1, treatment did not
      have an effect on the incidence of hyperketonemia (blood beta-hydroxybutyrate >=
      1.2 mmol/L; cumulative incidence to 3 wk postpartum of 28 to 30%), clinical
      health disorders, or udder edema. The prevalence of anovulation at 8 wk
      postpartum was 11% in the treatment group and 23% in the control but did not
      differ statistically given group-level randomization. Pregnancy at first
      insemination (33 and 35%) and median time to pregnancy to 200 d in milk (96 and
      97 d) were not different between treatment and control, respectively. No
      difference was observed between treatment groups in milk yield or components
      through the first 3 Dairy Herd Improvement Association test days (44 kg/d in both
      groups, accounting for parity and components). In experiment 2, there were no
      differences between treatment groups in feed intake. Mean blood beta
      hydroxybutyrate was lower at wk 3 in RPBC (0.6 vs. 0.9 +/- 0.12 mmol/L) with no
      difference between treatments for mean blood concentrations of fatty acids (wk -1
      or 1) and beta-hydroxybutyrate at wk 1 or 2. The gene for acyl-CoA oxidase 1
      (ACOX1) had lower mRNA abundance in RPBC with no difference between treatments
      for the other genes, but the expression of half of the genes assessed differed
      with days in milk. Liver triacylglycerol was lower in primiparous cows at 4 d in
      milk in RPBC (2.0 vs. 4.4 +/- 1.2%) but not at 14 d in milk (2.2 vs. 3.2 +/-
      0.97%) with no treatment effect in multiparous cows (4.6 +/- 0.8%). Accounting
      for parity, days in milk, fat and protein percentages, repeated test days, and a
      random effect of cow, no significant difference was observed between treatments
      in milk yield across the first 3 Dairy Herd Improvement Association tests (41.2
      +/- 1.3 in RPBC vs. 38.0 +/- 1.4 kg/d in control). Under the diet and management
      conditions of the field study including low prevalence of clinical health
      disorders, in experiment 1 we did not detect a benefit of RPBC, but in experiment
      2 liver fat content decreased in primiparous cows.

PMID- 30100512
TI  - Effect of dehydration and acidemia on the potassium content of muscle tissue and
      erythrocytes in calves with neonatal diarrhea.
AB  - Disturbances of extracellular potassium (K) homeostasis in calves with severe
      neonatal diarrhea have been studied extensively. Although total body depletion of
      this predominantly intracellular electrolyte is generally thought to occur in
      diarrheic calves, the mechanisms through which K depletion occurs are poorly
      understood. The aim of this study was to investigate how intracellular K
      homeostasis is affected by dehydration and acidemia, the 2 most important
      metabolic disturbances in calves with naturally occurring diarrhea. Twenty-seven
      calves with naturally occurring neonatal diarrhea, pronounced dehydration, and
      acidemia, and 2 groups of 10 healthy control calves were included in this study.
      Blood samples and muscle biopsies were obtained immediately before initiation of
      treatment (T0) and after complete rehydration and correction of acidemia (T1)
      from diarrheic calves. Blood samples were used to perform blood gas, blood
      biochemical, and hematological analyses and to determine K content in
      erythrocytes. Muscle biopsies were used to determine muscle tissue K content and
      tissue dry matter. Controls were used to determine values for erythrocyte and
      muscle tissue K content in healthy neonatal calves for comparison with diarrheic
      calves. As defined by the inclusion criteria, diarrheic calves showed pronounced
      acidemia and dehydration at T0. Mean muscle tissue K content and tissue dry
      matter remained unchanged between sampling times and did not differ from values
      measured in healthy control calves. Erythrocyte K content increased from 73.63 +/
      13.73 to 77.64 +/- 15.97 mmol/L (+/-standard deviation) but was associated with
      a concomitant decline in erythrocyte volume. Values measured at both sampling
      times in diarrheic calves did not differ from erythrocyte K measured in healthy
      control calves. The plasma K concentration (median [interquartile range])
      decreased from 5.44 [4.76-6.17] to 4.16 [3.99-4.31] mmol/L between T0 and T1.
      Although changes in plasma [K] were associated with the degree of dehydration,
      neither dehydration nor acidemia was associated with changes of K content in
      muscle tissue or erythrocytes. In conclusion, severe dehydration and acidemia in
      diarrheic calves were not associated with notable changes in K content of muscle
      tissue or erythrocytes. These results do not support the concept of pronounced K
      depletion occurring in calves with neonatal diarrhea. Erythrocytes are a poor
      surrogate tissue in which to measure changes of intracellular K content in
      diarrheic calves because of concomitant changes in erythrocyte volume that
      complicate the interpretation of results.

PMID- 30100513
TI  - In vitro immunogenicity of various native and thermally processed bovine milk
      proteins and their mixtures.
AB  - In vitro immunogenicity of various native and thermally processed (72 degrees
      C/15 s and 100 degrees C/30 s) bovine milk protein fractions, their mixtures,
      whey, and skim milk, was studied by analyzing the immune response of T helper
      (Th) cells in human peripheral blood mononuclear cells. The secretion of Th type
      cytokines induced by the protein stimulants was quantified while determining the
      heat-induced protein denaturation. Purified whey proteins, caseins and whey
      fraction, and skim milk provoked substantial immune responses at various degrees,
      indicating their potent immunogenicity. The protein mixtures prepared using the
      fractionated whey proteins with or without caseins appeared less immunogenic in
      both native and heat-treated forms, implying their potential of producing less
      immunogenic dairy products. The 100 degrees C/30 s treatment significantly
      altered the immunogenicity of most of the potent protein stimulants, which mostly
      coincided with their levels of protein denaturation. The 72 degrees C/15 s
      treatment caused the least protein denaturation but altered the immunogenicity of
      several protein stimulants notably, including heat-stable caseins and alpha
      lactalbumin.

PMID- 30100514
TI  - Short communication: The effect of calcium supplementation at calving on
      neutrophil function.
AB  - Low total blood calcium concentration after calving has been demonstrated to be a
      risk factor for reduced neutrophil function. The objective of this study was to
      evaluate whether administration of an injectable calcium supplement product soon
      after calving increased neutrophil oxidative burst or phagocytosis capacity. Cows
      (n = 27) from 4 farms were blocked by parity and randomly assigned to receive
      either calcium gluconate (35% wt/vol) in combination with calcium glucoheptonate
      (10% wt/vol; Theracalcium, Vetoquinol Canada Inc., Lavaltrie, Quebec, Canada) or
      a placebo within 12 h after calving and again 24 h later. Each dose of 120 mL was
      injected subcutaneously over 2 sites. Total serum calcium concentration,
      neutrophil oxidative burst, and neutrophil phagocytosis capacity were measured
      from coccygeal blood samples before (time 0) and 72 h after first treatment.
      There was no difference between treatment groups in lactation number, total
      calcium concentration, oxidative burst, or phagocytosis at time of enrollment.
      There was no effect of treatment on oxidative burst or phagocytosis by
      neutrophils. This preliminary study does not support an effect of supplemental
      calcium to improve neutrophil oxidative burst or phagocytosis capacity of low
      parity parturient cows.

PMID- 30100515
TI  - Antioxidant and antigenotoxic effect of dairy products supplemented with red
      ginseng extract.
AB  - The purpose of this study was to evaluate the antioxidant and antigenotoxic
      effect of dairy products milk (M) and yogurt (Y) after the addition of 2% red
      ginseng extract to milk (RM) and to yogurt (RY). Total phenolic content, total
      flavonoid content, 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity,
      oxygen radical absorbance capacity, and total radical trapping antioxidant
      potential were determined in the samples. Furthermore, antigenotoxic effect of
      samples was measured, using comet assay in human leukocytes. Total phenolic
      content and total flavonoid content of RM [38.3 +/- 0.8 mg of gallic acid
      equivalents (GAE)/100 g, 23.6 +/- 0.1 mg of quercetin equivalents (QE)/100 g] and
      RY (41.1 +/- 0.9 mg of GAE/100 g, 18.7 +/- 0.1 mg of QE/100 g), respectively,
      were higher than those of M (6.31 +/- 0.2 mg of GAE/100 g, 10.4 +/- 0.1 mg of
      QE/100 g) and Y (8.1 +/- 0.9 mg of GAE/100 g, 8.4 +/- 0.2 mg of QE/100 g),
      respectively. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity and
      oxygen radical absorbance capacity values increased significantly after the
      addition of 2% red ginseng in both. Additionally, the total radical trapping
      antioxidant potential in RM (787.7 +/- 7.0 MUg/mL) was lower than in M (2074.0 +/
      28.4 MUg/mL). The H2O2-induced DNA damage in RY (0.1 +/- 0.0 mg/mL) was less
      than the damage in Y (0.4 +/- 0.0 mg/mL), but we found no significant difference
      between M and RM. This study indicates that supplementation with red ginseng can
      fortify the antioxidant and antigenotoxic effects of dairy products effectively.

PMID- 30100516
TI  - Claw horn lesions in mid-lactation primiparous dairy cows under pasture-based
      systems: Association with behavioral and metabolic changes around calving.
AB  - The objectives of this study were to describe the lying behavior of primiparous
      dairy cows under pasture-based systems during the pre- and postcalving period and
      characterize the association of lying behavior and analytes related to energy
      metabolism during this period with claw horn disruption lesion development later
      in lactation. Our convenience sample included 39 primiparous Holstein cows from 3
      commercial farms that were assessed for body condition score (BCS; 5-point scale,
      0.25-point increments) and had blood collected at wk -3, -2, -1, 1, 2, and 3
      relative to calving date. Blood samples were assayed for nonesterified fatty
      acids, beta-hydroxybutyrate (BHB), and cholesterol concentrations. Electronic
      data loggers (HOBO Pendant G Acceleration, Onset Computer Corporation, Bourne,
      MA) recorded lying behavior at 1-min intervals from 3 wk before calving to 3 wk
      after calving. Starting at 4 wk after calving and until 16 wk after calving, cows
      were examined for claw lesions at approximately 4-wk intervals. Sole lesions and
      white line lesions were scored on a 0 to 10 scale. Of the 39 primiparous cows, 19
      cows scored 0 at all exams during the entire study period and 20 cows had at
      least 1 severe lesion (score >=4) between 8 and 16 wk after calving. Time spent
      lying before calving averaged 10.3 +/- 0.3 h/d, but declined to 7.3 +/- 0.3 h/d
      after calving (least squares means +/- standard error). At calving, we noted an
      increase in the number of lying bouts (12.9 +/- 0.45 bouts/d) compared with the
      pre- and postcalving averages of 11.6 (+/-0.53) and 9.1 (+/-0.47) bouts,
      respectively. Cows that developed claw lesions later in mid lactation spent less
      time lying down than cows without lesions during wk 3 after calving compared with
      healthy cows (7.29 +/- 0.22 vs. 8.51 +/- 0.16 h/d). Lesion cows had fewer lying
      bouts per day, and these bouts were of longer duration than no-lesion cows after
      calving. Increased odds of lesion were found to be associated with shorter lying
      times and fewer number of lying bouts during wk 3 (odds ratio = 1.23).
      Nonesterified fatty acids (747 +/- 58 vs. 990 +/- 86.85 umol/L) and BHB (0.77 +/-
      0.06 vs. 0.60 +/- 0.04 mmol/L) concentrations during wk 1 were greater in cows
      that developed claw lesions relative to cows that did not develop lesions. The
      BHB concentrations also remained higher in wk 2 for cows that developed claw
      lesions (0.63 +/- 0.04 vs. 0.46 +/- 0.03 mmol/L) compared with cows that did not
      develop any lesions. Cows that developed lesions experienced greater losses in
      BCS from wk -3 to 3 than cows without lesions (0.74 +/- 0.01 and 0.61 +/- 0.01
      BCS change, respectively). In summary, changes in lying behavior and energy
      metabolic status after calving were associated with claw horn disruption lesions
      in mid-lactation primiparous cows under pasture-based systems.

PMID- 30100517
TI  - Targeting Mitochondrial Metabolism in Neuroinflammation: Towards a Therapy for
      Progressive Multiple Sclerosis.
AB  - The lack of effective treatment options for chronic neurological conditions, such
      as multiple sclerosis (MS), highlights the need to re-evaluate disease
      pathophysiology in the process of identifying novel therapeutic targets. The
      persistent activation of mononuclear phagocytes (MPs) is one of the major drivers
      of neurodegeneration and it sustains central nervous system (CNS) damage.
      Mitochondrial metabolism influences the activity of MPs, and the metabolites that
      they produce have key signalling roles in inflammation. However, how changes in
      immune cell metabolism sustain a chronic state of neuroinflammation is not fully
      understood. Novel molecular and cellular therapies for chronic neuroinflammation
      should be developed to target mitochondrial metabolism in innate immune cells to
      prevent secondary neurological damage and the accumulation of irreversible
      disability in patients.

PMID- 30100518
TI  - Psychosocial interventions for reduction of distress in children with leukemia
      during bone marrow aspiration and lumbar puncture.
AB  - BACKGROUND: Children with cancer undergo many invasive medical procedures that
      are often painful and highly distressing, including bone marrow aspiration (BMA)
      and lumbar puncture (LP). Psychosocial interventions have been demonstrated to
      reduce children's distress resulting from invasive medical procedures. The aim of
      the study is to assess the efficacy of psychosocial interventions to reduce
      distress in children with cancer undergoing BMA and LP in a pediatric cancer
      center in Taiwan. METHODS: Children with cancer who received treatment between
      March 2015 and December 2016 at Chang Gung Memorial Hospital, Linkou, Taiwan were
      eligible for the study. The psychosocial intervention comprised preparation and
      cognitive behavioral intervention and was provided by a certified child life
      specialist. The assessment instrument was the revised version of the
      Observational Scale of Behavioral Distress (OSBD-R). The behavioral distress of
      patients who underwent psychosocial interventions for BMA and LP was compared
      with patients without interventions. We also analyzed the difference of
      behavioral distress in patients' pre- and post-psychosocial intervention for BMA
      and LP. RESULTS: Eighteen patients were enrolled into this study. The mean age of
      diagnosis of leukemia was 6.6 years old (range: 3-11 years). Fifteen patients
      were diagnosed with acute lymphoblastic leukemia, and 3 were diagnosed with acute
      myeloid leukemia. The mean of OSBD-R total scores in 7 patients with psychosocial
      intervention was significantly lower than the mean score in 6 patients without
      intervention (0.65 vs. 4.81, p = 0.002). Pre- and post-psychosocial intervention
      for BMA and LP behavioral distress were evaluated for the remaining 5 patients.
      Consistently, there was a significant reduction of the OSBD-R score following
      interventions (3.04 vs. 7.81, p = 0.025). CONCLUSION: Psychosocial interventions
      provided by a certified child life specialist have a significant potential to
      reduce children's distress during BMA and LP in pediatric healthcare settings in
      Taiwan.

PMID- 30100519
TI  - Early predictors of neonatal hyperbilirubinemia in full term newborn.
AB  - BACKGROUND: Reliable predictive markers enabling physicians to identify which
      newborns will develop significant hyperbilirubinemia have become mandatory for
      prevention of severe hyperbilirunemia. We aimed at determining the critical cord
      serum bilirubin and albumin levels and bilirubin/albumin ratio early as reliable
      markers. STUDY DESIGN: This prospective study included 175 full-term neonates.
      Measurement of cord bilirubin, albumin and bilirubin/albumin ratio was done to
      predict significant hyperbilirubinemia in healthy term newborns based on serum
      bilirubin measurements made within 5 days of life. RESULTS: Most cases that
      developed significant neonatal hyperbilirubinemia (67.9%) had cord albumin level
      <= 2.8 gm/dl. Cord Bilirubin/albumin ratio cut off value > 0.61 had a good
      predictive value with a sensitivity of 100% and specificity of 88.4%, and cord
      serum albumin cut off value <= 3.0 mg/dl also had a good predictive value with a
      sensitivity of 85.7% and specificity of 67.3%. ROC curve analysis of cord total
      bilirubin demonstrated that a cut off value of >=1.84 mg/dl had a good predictive
      value with a sensitivity of 100.0% and specificity of 87.1%. CONCLUSION: Cord
      bilirubin/albumin ratio, serum bilirubin and albumin could be early predictors
      for neonatal hyperbilirubinemia.

PMID- 30100520
TI  - Association of VEGFA polymorphisms with necrotizing enterocolitis in Chinese Han
      population.
AB  - BACKGROUND: To examine whether polymorphisms in the VEGFA gene lead to low VEGFA
      production in peripheral blood and increased risk of NEC in the Chinese Han
      population. MATERIAL AND METHODS: Thirty NEC patients and 80 control subjects
      were enrolled. Six VEGFA single-nucleotide polymorphisms (SNPs) were performed
      using the SEQUENOM MassARRAY platform assay. The concentration of VEGFA in the
      plasma was measured using an enzyme-linked immunosorbent assay. RESULTS: The
      rs699947 and rs833061 VEGF-A SNPs were found to be associated with low plasma
      levels and high risk of NEC. CONCLUSION: Our results suggested that, if validated
      in larger studies, screening for VEGFA SNPs and plasma levels might be useful as
      a risk factor for NEC in the future.

PMID- 30100522
TI  - Editorial commentary: Re-inventing chronic disease management as a service -
      Medication adherence solutions are ground zero.

PMID- 30100521
TI  - Being Facilitators in a Challenging Context-School Personnel's Experiences of
      Caring for Youth with Diabetes Type 1.
AB  - PURPOSE: The purpose of the study was to describe school personnel's experiences
      of caring for youth with diabetes type 1. DESIGN AND METHODS: A qualitative
      design was chosen for this study. Data were collected with individual interviews
      that were subjected to inductive qualitative content analysis. The sample
      consisted of 24 school personnel (teachers, principals and school nurses) from
      Swedish schools. All had experience with youth aged 6 to 18 years old with
      diabetes type 1. RESULTS: School personnel experienced caring for youth with
      diabetes type 1 as "Being facilitators in a challenging context" and described
      establishing trusting relationships, finding strategies to support self-care,
      feeling uncertain and incapable in need of education, and dealing with unclear
      responsibility. CONCLUSIONS: School personnel (teachers, principals and school
      nurses) are key professionals supporting youth with diabetes type 1 and self-care
      in school. Lack of education and unclear responsibility created feelings of
      uncertainty and insecurity for school personnel and a need for mandatory
      education of school personnel regarding T1DM and self-care, including legislation
      was identified. IMPLICATIONS: Mandatory education should be provided for all
      school personnel regarding diabetes type 1, self-care and current legislation. A
      liason position in form of a nurse specialist should manage the education.

PMID- 30100523
TI  - A novel mba-based Real time PCR approach for genotyping of Ureaplasma parvum
      validated in a cohort of Mongolian mothers and offspring.
AB  - The role of Ureaplasma parvum in abnormal outcomes of human pregnancy has been
      discussed controversially in the past. Of the 14 known ureaplasma serovars, the
      Ureaplasma parvum serovars 1, 3, 6 and 14, have been found to derive from smaller
      genomes. Serovars 3 and 6 have been described more often to cause complications
      in pregnancy. To elucidate the serovar distribution in U. parvum positive
      specimens of 200 Mongolian mothers and their offspring, a new set of mba
      targeting PCRs was developed enabling a fast and reliable serovar differentiation
      by melting peak analysis in a Real time PCR approach or by conventional agarose
      gel electrophoresis. 92% maternal and 55% neonatal samples were retrospectively
      genotyped and a dominance of serovars 3 and 6 was detected while serovar 14 was
      almost absent. Transmission from mothers to newborns was detected in 83% of U.
      parvum positive neonates exhibiting serovar patterns identical to their mothers.
      No statistically significant correlation between a distinct serovar and pregnancy
      outcome could be detected. However, neonatal colonization with serovar 1 declined
      with progressing pregnancy suggesting that a higher ureaplasma load shortened
      pregnancy and thereby had a potential negative effect on offspring health. Our
      novel mba-based Real time PCR approach, which can also be used in conventional
      PCR and gel electrophoretic analysis, provides the proof of principle that the
      four U. parvum serovars 1, 3, 6 and 14 can be differentially detected and
      quantified. A larger scale study outside the scope of this work should be
      conducted to clarify the impact of serovar 1 on pregnancy outcome.

PMID- 30100524
TI  - Necrotizing enterocolitis comes in different forms: Historical perspectives and
      defining the disease.
AB  - The specific cause of what is commonly referred to as necrotizing enterocolitis
      (NEC) disease has been elusive largely because it is becoming clear that this
      entity represents more than one disease with multifactorial pathogenic
      mechanisms. Furthermore, finding clear and consistent diagnostic biomarkers will
      be difficult until the different subsets of what we are calling this disease are
      better delineated. In this introductory chapter, we discuss different disease
      entities that are frequently termed "NEC" in the newborn infant. We hope this
      will set the stage for more focused research and development of preventative
      measures for at least the most common forms of this disease.

PMID- 30100525
TI  - Predictive kinetic optimisation of hydrophilic interaction chromatography *
      reversed phase liquid chromatography separations: Experimental verification and
      application to phenolic analysis.
AB  - Method development and optimisation for comprehensive two-dimensional liquid
      chromatography (LC * LC) is complex, since this involves the intricate
      relationships between a large number of experimental parameters with the aim of
      achieving three conflicting goals: maximising separation performance (peak
      capacity), minimising analysis time and minimising dilution. This is especially
      true for the on-line combination of hydrophilic interaction chromatography
      (HILIC) and reversed phase LC (RP-LC) due to the relative elution strengths of
      the mobile phases used in these modes, which has severe implications for the
      modulation process and dilution. In this study we report a predictive kinetic
      optimisation tool for on-line HILIC * RP-LC which is based on theoretical
      relationships between the optimisation goals, the target analyte properties and
      chromatographic parameters (column dimensions, flow rates, mobile phases,
      injection volumes, etc.), allowing all chromatographic parameters to vary
      simultaneously within defined ranges. Experimental restrictions, such as pressure
      limits, flow rates, etc., are enforced to ensure all results are practically
      achievable on a given instrumental configuration. A Pareto-optimality approach is
      then used to obtain optimal sets of experimental conditions, from which the
      one(s) best satisfying the requirements in terms of time, dilution and/or peak
      capacity can be chosen. To overcome the challenges associated with mobile phase
      incompatibility in the coupling of HILIC and RP-LC, splitting of the first
      dimension HILIC flow, dilution with an aqueous make-up, or a combination of both,
      were investigated to establish the best approach to minimise total dilution and
      maximise performance. The validity of the methodology is demonstrated by deriving
      optimal conditions for the HILIC * RP-LC separation of procyanidins on selected
      columns and subsequent experimental verification of the performance for the
      separation of a cocoa extract.

PMID- 30100526
TI  - On-line incubation and real-time detection by ultra-performance liquid
      chromatography-quadrupole time-of-flight mass spectrometry for rapidly analyzing
      metabolites of anthraquinones in rat liver microsomes.
AB  - The traditional studies on metabolism in liver microsomes were carried out in off
      line form. In this paper, a rapid and convenient method for the study of
      metabolism of substrates in liver microsomes was established by means of ultra
      performance liquid chromatography-quadrupole time-of-flight mass spectrometry
      (UPLC-Q-TOF/MS): on-line incubation and real-time detection of substrates in
      liver microsomes. The liver microsomal incubation system was placed in a sample
      chamber at 37  degrees C. On-line solid phase extraction (SPE) column was used
      for on-line sample treatment, its function was to enrich the drug prototype and
      its metabolites with weak polarity, and elute the phosphate in the samples. The
      incubation samples were analyzed by setting appropriate injection time, liquid
      phase elution procedure and mass spectrometry acquisition time. The phase I
      metabolites of anthraquinone compounds, aloe-emodin (A), rhein (R), emodin (E),
      chrysophanol (CP), physcion (PS) and their glucosides, were analyzed through this
      method. The results showed that 8 anthraquinone compounds underwent metabolic
      reactions such as hydrolysis, oxidation, reduction and hydroxylation in liver
      microsomal incubation system. In addition, a certain degree of mutual
      transformation of anthraquinones in liver microsomal incubation system was found.
      The results provide a reference for in vivo metabolism of anthraquinones in
      rhubarb. On-line incubation and real-time detection is a feasible, convenient and
      rapid method for the analysis of drug metabolism in vitro.

PMID- 30100528
TI  - Primary care workforce development in Europe: An overview of health system
      responses and stakeholder views.
AB  - Better primary care has become a key strategy for reforming health systems to
      respond effectively to increases in non-communicable diseases and changing
      population needs, yet the primary care workforce has received very little
      attention. This article aligns primary care policy and workforce development in
      European countries. The aim is to provide a comparative overview of the
      governance of workforce innovation and the views of the main stakeholders. Cross
      country comparisons and an explorative case study design are applied. We combine
      material from different European projects to analyse health system responses to
      changing primary care workforce needs, transformations in the general
      practitioner workforce and patient views on workforce changes. The results reveal
      a lack of alignment between primary care reform policies and workforce policies
      and high variation in the governance of primary care workforce innovation.
      Transformations in the general practitioner workforce only partly follow changing
      population needs; countries vary considerably in supporting and achieving the
      goals of integration and community orientation. Yet patients who have experienced
      task shifting in their care express overall positive views on new models. In
      conclusion, synthesising available evidence from different projects contributes
      new knowledge on policy levers and reveals an urgent need for health system
      leadership in developing an integrated people-centred primary care workforce.

PMID- 30100527
TI  - Detection of pacific ciguatoxins using liquid chromatography coupled to either
      low or high resolution mass spectrometry (LC-MS/MS).
AB  - Ciguatera Fish Poisoning (CFP) is primarily caused by consumption of tropical and
      sub-tropical fish contaminated by Ciguatoxins (CTXs). These lipid-soluble,
      polyether neurotoxins are produced by dinoflagellates in the genera Gambierdiscus
      and Fukuyoa. While there is no regulatory level in Europe for CTXs, the European
      Food Safety Authority (EFSA) adopted the United States guidance level of 0.01 MUg
      P-CTX1B eq.kg-1 of fish. This limit is extremely low and requires significant
      improvement in the detection of CTXs. In this study, we compared analytical
      protocols based on liquid chromatography coupled to tandem low or high resolution
      mass spectrometry (LC-LRMS or HRMS) to find the best conditions for sensitivity
      and/or selectivity. Different approaches such as LC conditions, ion choice and
      acquisition modes, were evaluated to detect the Pacific-ciguatoxins (P-CTXs) on a
      triple quadrupole (API4000 Qtrap, Sciex) or a quadrupole time of flight (QTOF
      6550, Agilent Technologies) spectrometer. Moreover, matrix effects were
      calculated using matrix-matched calibration solutions of P-CTX1B and P-CTX3C
      prepared in purified fish extract. Subsequently, the method performance was
      assessed on naturally contaminated samples of seafood and phytoplankton. With
      LRMS, the ammoniated adduct ion used as a precursor ion showed an advantage for
      selectivity through confirmatory transitions, without affecting signal-to-noise
      ratios, and hence limits of detection (LODs). As also reported by some studies in
      the literature, methanol-based mobile phase gave better selectivity and
      sensitivity for the detection of P-CTXs. While the LOD for P-CTX1B and P-CTX3C
      met the EFSA recommendation level when using LRMS, the findings suggested careful
      evaluation of instrumental parameters for determination of CTXs. LODs were
      significantly higher for HRMS, which currently results in the need for a
      significantly higher sample intake. Nevertheless, HRMS allowed for the
      identification of artefacts and may allow for improved confirmation of the
      identity of P-CTXs analogues. Consequently, LRMS and HRMS are considered
      complementary to ensure adequate quantitation and identification of P-CTXs.

PMID- 30100529
TI  - The introduction of electronic medical records in France: More progress during
      the second attempt.
AB  - To support care coordination, a national electronic medical record (DMP), has
      been created by law in 2004. Because of technical difficulties and delays during
      implementation, the project was entrusted to a dedicated technical agency in
      2009. But 3 years later, only 160,000 DMPs had been opened contrary to the
      several million expected. Physicians criticized the technical and administrative
      burden, but the main factors highlighted were resistance to sharing information
      with patients and with other professionals. Failing to cross the critical
      threshold of users that gives value to the system, the project failed. After this
      first attempt, the project was entrusted by law to the national health insurance
      fund in 2016. The new policy was addressed to patients, professionals and
      software companies. The policy has allowed patients to independently access and
      modify their DMP data already in possession of the national public medical
      insurance, and has introduced financial incentives for physicians opening a DMP.
      As a result the deployment of DMPs has accelerated substantially: 350,000 new
      DMPs were opened in nine pilot departments within a year. If scaled-up to the
      entire country, this number would correspond to 4 million DMPs.

PMID- 30100531
TI  - [Erratum to "Study of the feasibility of spirometry in general practice" Rev Mal
      Respir 2018;35:238-248].

PMID- 30100530
TI  - [COLT: Ten years of research in lung transplantation, results and perspectives].

PMID- 30100532
TI  - Decreasing subthalamic deep brain stimulation frequency reverses cognitive
      interference during gait initiation in Parkinson's disease.
AB  - OBJECTIVE: Freezing of gait (FOG) represents a major burden for Parkinson's
      disease (PD) patients. High-frequency (130-Hz) subthalamic deep-brain-stimulation
      (STN-DBS) has been reported to aggravate FOG whereas lowering the frequency to 60
      80 Hz improves FOG. To further understand the effects of STN-DBS on FOG, we
      assessed the effects of 80-Hz and 130-Hz STN-DBS on gait initiation performance,
      in relation to motor and executive function processing. METHODS: Gait initiation
      was recorded in 19 PD patients and 20 controls, combined or not with a cognitive
      interference task with a modified Stroop paradigm. PD patients were recorded
      before surgery with and without dopaminergic treatment, and after surgery with 80
      Hz and 130-Hz STN-DBS in a randomised double-blind crossover study. RESULTS: In
      the absence of cognitive interference, PD patients exhibited significant gait
      initiation improvement with dopaminergic treatment, 80-Hz and 130-Hz STN-DBS.
      Nine patients performed the cognitive interference task. With 130-Hz STN-DBS, all
      gait initiation parameters were significantly degraded, whereas the cognitive
      interference task induced no major changes before surgery and with 80-Hz STN-DBS,
      as in controls. CONCLUSIONS: High-frequency STN-DBS leads to an inability to
      simultaneously process motor and cognitive information while this ability seems
      preserved with low-frequency STN-DBS. SIGNIFICANCE: This study supports the
      potential benefit of 80-Hz STN-DBS on FOG.

PMID- 30100533
TI  - pH-permeability profiles for drug substances: Experimental detection, comparison
      with human intestinal absorption and modelling.
AB  - The influence of pH on human intestinal absorption is frequently not considered
      in early drug discovery studies in the modelling and subsequent prediction of
      intestinal absorption for drug candidates. To bridge this gap, in this study,
      experimental membrane permeability data were measured for current and former drug
      substances with a parallel artificial membrane permeability assay (PAMPA) at
      different pH values (3, 5, 7.4 and 9). The presented data are in good agreement
      with human intestinal absorption, showing a clear influence of pH on the
      efficiency of intestinal absorption. For the measured data, simple and general
      quantitative structure-activity relationships (QSARs) were developed for each pH
      that makes it possible to predict the pH profiles for passive membrane
      permeability (i.e., a pH-permeability profile), and these predictions coincide
      well with the experimental data. QSARs are also proposed for the data series of
      highest and intrinsic membrane permeability. The molecular descriptors in the
      models were analysed and mechanistically related to the interaction pattern of
      permeability in membranes. In addition to the regression models, classification
      models are also proposed. All models were successfully validated and blind tested
      with external data. The models are available in the QsarDB repository
      (http://dx.doi.org/10.15152/QDB.203).

PMID- 30100534
TI  - Contradictory results of serological confirmatory test and real-time PCR assays
      in diagnosis a patient of HIV-1 infection.
AB  - Human immunodeficiency virus (HIV)/AIDS is a major public health problem
      worldwide. Here we report the case of a patient with positive HIV-1 serology and
      negative result of The COBAS AmpliPrep/COBAS Taqman HIV-1 Test version 2.0
      (CAP/CTM v2.0) assay (Roche Diagnostics) for HIV-1 RNA quantification in the
      absence of antiretroviral therapy (ARV). Considering the HIV contact history and
      repeating serological confirmatory test is essential before considering a low or
      even undetectable HIV-1 viral load to be a false-negative result.

PMID- 30100535
TI  - An epidemiological study of dengue and its coinfections in Delhi.
AB  - OBJECTIVES: To study the epidemiology of dengue with reference to serological,
      demographic profile, spatio-temporal distribution, vectors, circulating serotypes
      and coinfections. METHODS: Demographic data and presenting symptoms of fever
      cases reporting to the clinic were recorded. Suspected patients were tested for
      dengue, chikungunya and malaria. Dengue specific RT-PCR was performed to detect
      circulating DENV serotypes. Vector surveys were carried out to detect Aedes
      breeding. RESULTS: Of the 5536 fever patients tested during 2012 to 2015, 1536
      (27.7%) had confirmed dengue. The peak in dengue positivity was observed during
      September and October. Of the 60 samples analysed, 10 (16.7%) had concurrent
      infection with multiple dengue serotypes; one of them had all the four serotypes.
      Coinfection of dengue with malaria and chikungunya was also observed. The
      occurrence of dengue and malaria was inversely related. Seven percent of the
      dengue patients required hospitalization. Vector surveys in the draining area
      revealed Aedes breeding with a high house index. CONCLUSION: Delhi being
      hyperendemic, the occurrence of concurrent infections with multiple DENV
      serotypes has become a frequent finding. The study emphasizes the need of
      epidemiological and entomological surveillance to monitor trends in dengue
      distribution, seasonal patterns and circulating serotypes to guide dengue control
      activities.

PMID- 30100537
TI  - Effect of clients Strategic Index Case Testing on community-based detection of
      HIV infections (STRICT study).
AB  - BACKGROUND: Strategic Index Case Testing (STRICT), a form of partner notification
      service, was initiated to track, identify and notify sexual partners of people
      living with HIV (Index clients) with the sole aim of testing them to determine
      their HIV status and linking clients who are positive to Anti-Retroviral Therapy
      (ART). This research analyzed the HIV sero-prevalence among sexual partners of
      HIV positive clients using STRICT and determines the role of STRICT in HIV
      epidemic control. METHODS: This is a non-control Interventional study that
      determined the impact of Strategic Index Case Testing (STRICT) on detecting
      previously undiagnosed HIV infections among sexual partners of positive index
      clients. This study was conducted in seven Local Government Areas (LGAs) of Karu,
      Nasarawa, Lafia, Doma, AMAC, Bwari, and Ushongo. These LGAs were selected for HIV
      epidemic control due to projected high prevalence of HIV from previous program
      level data. HTS was offered to sexual partners of index PLHIV from facility and
      community within the LGAs. Index clients were PLHIV diagnosed from outreaches,
      hot spots set up in strategic places and Provider Initiated Testing and
      Counseling (PITC) in comprehensive and primary health care facilities. Newly
      diagnosed PLHIV and those already enrolled and commenced on ART from October 2015
      to July 2016 were identified from source registers. These index clients were
      counseled on how to notify their sexual partners about their HIV status and on
      bringing them for HIV Testing and Counseling (HTS). Those unable to do so after a
      given period of time were assisted by health workers in informing their various
      sexual partners based on the confidential agreement and informed consent signed
      by the Index clients. FINDINGS: A total of 1277 index cases were counseled and
      interviewed with 879 index clients agreeing to disclosure, giving a disclosure
      rate of 68.3%. We identified 888 sexual partners from the interviews and traced
      870 (97.9%) sexual contacts. A total of 741 (85.2%) of 870 sexual contacts traced
      were tested for HIV, out of which 378 (51%) tested positive using an HIV rapid
      test kit, and this was statistically significant at P Value=0.0254. A total of
      348 (92.1%) out of 378 HIV positive sexual partners were immediately commenced on
      ART using the recommended UNAIDS Test and Treat approach to HIV epidemic control.
      INTERPRETATION: STRICT identifies the need for reaching out to sexual partners of
      index clients and providing them with HIV Testing Services (HTS) as they belong
      to a high risk priority population and also linking them to care and treatment.
      This group of people must be reached with HTS strategies in order to end the HIV
      epidemic as evidenced by high sero-prevalence of 51% among them.

PMID- 30100536
TI  - Clinical characteristics and etiology of bacterial meningitis in Chinese children
      >28 days of age, January 2014-December 2016: A multicenter retrospective study.
AB  - OBJECTIVE: To explore the clinical characteristics and etiology of bacterial
      meningitis (BM) in Chinese children. METHOD: BM cases in children 28days to 18
      years old were collected from January 2014-December 2016 and screened according
      to World Health Organization standards. Clinical features, pathogens, and
      resistance patterns were analyzed. RESULTS: Overall, 837 cases were classified
      into five age groups: 28 days-2 months (17.0%), 3-11 months (27.8%), 12-35 months
      (24.0%), 3-6 years (13.9%), and >6years (17.3%). Major pathogens were
      Streptococcus pneumoniae (S. pneumoniae, n=136, 46.9%), group B Streptococcus
      (GBS, n=29, 10.0%), and Escherichia coli (E. coli, n=23, 7.9%). In infants <3
      months old, GBS (46.5%) and E. coli (23.3%) were most common; in children >3
      months old, S. pneumoniae (54.7%), which had a penicillin non-susceptibility rate
      of 55.4% (36/65), was most frequent. The resistance rates of S. pneumoniae and E.
      coli to cefotaxime and ceftriaxone were 14.0%/40.0% and 11.3%/68.4%,
      respectively. All GBS isolates were sensitive to penicillin. CONCLUSIONS: The
      occurrence of BM peaked in the first year of life, while S. pneumoniae was the
      predominant pathogen in children >3months of old. The antibiotic resistance of S.
      pneumoniae was a concern.

PMID- 30100538
TI  - Pentoxifylline versus Steroid Therapy for Idiopathic Sudden Sensorineural Hearing
      Loss with Diabetes.
AB  - OBJECTIVES: To compare the efficacy of pentoxifylline with that of conventional
      steroid therapy in diabetic patients with idiopathic sudden sensorineural hearing
      loss (ISSNHL) and to compare blood sugar levels during hospitalization. MATERIALS
      AND METHODS: Medical charts were retrospectively reviewed for all diabetic
      patients admitted to one institution for ISSNHL between 2000 and 2015. We
      analyzed 298 cases; 50 patients received pulse steroid treatment (steroid group)
      and 248 received intravenous administration of pentoxifylline only
      (pentoxifylline group). Hearing change was evaluated by comparing the initial
      hearing tests with follow-up hearing tests for up to 3 months. Blood sugar levels
      were also compared between the 2 groups. RESULTS: At 3 months post-treatment, the
      degree of hearing recovery was similar between the 2 groups. The pure-tone
      average was improved from baseline by 17.9+/-21.2 dB in the steroid group and
      18.9+/-20.7 dB in the pentoxifylline group (p=0.776); hearing recovery rates were
      also similar (40% vs 39.1%; p=0.826). During hospitalization, average fasting
      blood sugar levels were higher (203.9+/-92.0 vs 174.4+/-54.8 mg/dL; p=0.033) and
      acute hyperglycemia was more common (48.0% vs 33.1%; p=0.044) with steroid versus
      pentoxifylline treatment. CONCLUSION: Hearing recovery rates did not
      significantly differ between steroid and pentoxifylline treatment in diabetic
      patients with ISSNHL, but pentoxifylline appeared to be associated with better
      blood sugar control.

PMID- 30100540
TI  - Contemporary Molecular Biology of Sporadic Vestibular Schwannomas: A Systematic
      Review and Clinical Implications.
AB  - In light of missing systematic reviews in the literature, the objective of this
      paper is to present the contemporary knowledge on the molecular biology of
      vestibular schwannomas (VS), based on a systematic literature search. In
      addition, current and prospected medical therapy based on molecular biology is
      addressed. A systematic literature search was conducted using the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The
      systematic search was performed in the Pubmed and Embase databases. The following
      were the words searched: acoustic neuroma/vestibular schwannoma, molecular
      biology, gene, and microRNA. Specific inclusion and exclusion criteria were
      determined prior to search. The systematic search rendered 486 articles,
      ultimately yielding 69 included articles, whereas 35 were from relevant
      references. The occurrence of at least one mutation in the merlin gene was
      reported to range between 54% and 76%, whereas the loss of heterozygosity (LOH)
      corresponding to chromosome 22 occurs in 25% to 83% of sporadic VS. Global gene
      expression studies indicate that a number of genes other than merlin are at play.
      No high-level methylation of the merlin gene has been found. Several miRNAs are
      deregulated in tumor tissue, among others let-7d, miR-221, and miR-21. The
      acquired knowledge on molecular biology has led to several clinical
      implementations. Lack of the tumor suppressor merlin plays a principal role in
      the development of VS. Existing knowledge on the molecular biology has led to the
      first attempts of targeted medical treatment to prevent tumor growth. Future
      research is likely to introduce potential imaging markers with prognostic value
      and new targets for medical therapy.

PMID- 30100539
TI  - Natural History of Tympanic Membrane Retraction in Children with Cleft Palate.
AB  - OBJECTIVES: The natural history of tympanic membrane retraction is unpredictable.
      To obtain prognostic information for guiding surveillance and treatment, a cohort
      of children with retraction from cleft palate were prospectively followed for
      over 5 years. MATERIALS AND METHODS: This was a prospective observational study
      at a tertiary academic institution. Children with pars tensa retraction were
      selected from a cohort of 143 children with cleft palate. Thirty-seven ears were
      assessed with otoendoscopic image capture and audiometry at a median age of 9
      years and reassessed at a median follow-up interval of 6.4 years. The severity of
      tympanic membrane retraction in the serial images of each ear was compared by
      four pediatric otolaryngologists blinded to the dates of the images. RESULTS:
      Initially, 19/37 retractions (51%) demonstrated contact with the incus and/or
      promontory. Follow-up images were rated as stable (n=16) or better (n=12) for
      28/37 retractions (76%). Of the nine retractions that became more extensive, two
      developed cholesteatoma (5% of the total). No ossicular erosion developed in ears
      without cholesteatoma. Conductive hearing loss (4-tone average air-bone gap >25
      decibels hearing level) was initially present in five ears, worsened in one, and
      normalized without intervention in others. No ears with initial normal hearing
      developed hearing loss. CONCLUSION: Most tympanic membrane retractions remained
      stable or improved over time in this cohort of children who were at a risk of
      persistent eustachian tube dysfunction. Clinically significant progression
      occurred infrequently, justifying the conservative approach taken to manage these
      retractions. Such data are necessary to weigh the potential benefit of preventive
      intervention over observation.

PMID- 30100541
TI  - Classifications of Mastoid and Middle Ear Surgery: A Scoping Review.
AB  - OBJECTIVES: The aim of this scoping review was to evaluate existing
      classifications of surgical procedures of the middle ear and mastoid and find a
      suitable classification that could serve as an international standard. MATERIALS
      AND METHODS: Scoping review with a systematic literature search using reference
      tracking and a syntax including all surgical procedures in mastoid and middle ear
      surgery and their synonyms. Studies were selected based on inclusion and
      exclusion criteria. RESULTS: Eleven reported classifications were included; six
      of which focused on middle ear surgery, two on mastoid surgery, and three on
      both. However, none of the classifications included all current surgical
      procedures of mastoid and middle ear surgery. CONCLUSION: Many classifications
      have been proposed for innumerable surgical techniques in middle ear and mastoid
      surgery. Some are outdated, some are incomplete, most are not widely accepted,
      and only few correspond with all current surgical techniques.

PMID- 30100542
TI  - Atraumatic Scala Tympani Cochleostomy; Resolution of the Dilemma.
AB  - OBJECTIVES: While an accurate placement in cochleostomy is critical to ensure
      appropriate insertion of the cochlear implant (CI) electrode into the scala
      tympani (ST), the choice of preferred cochleostomy sites widely varied among
      experienced surgeons. We present a novel technique for precise yet readily
      applicable localization of the optimum site for performing ST cochleostomy.
      MATERIAL AND METHODS: Twenty fresh frozen temporal bones were dissected using the
      mastoidectomy-posterior tympanotomy approach. Based on the facial nerve and the
      margins of the round window membrane (RWM), the cochleostomy site was chosen to
      insert the electrode into the ST while preserving the surrounding intracochlear
      structures. RESULTS: There is a limited safe area suitable for the ST
      implantation in the area inferior and anterior to the RWM. There is a higher risk
      of scala vestibuli (SV) insertion anterior to that area. Posterior to that area,
      the cochlear aqueduct (CA) and inferior cochlear vein (ICV) are liable for the
      injury. CONCLUSION: For atraumatic CI, precise and easy localization of the site
      of cochleostomy play a pivotal role in preserving intracochlear structures.
      Accurate setting of the vertical and horizontal orientations is mandatory before
      choosing the site of cochleostomy. The facial nerve and the margins of the RWM
      offer a very helpful clue for such localization; meanwhile, it is readily
      identifiable in the surgical field.

PMID- 30100543
TI  - The Association of GRM7 Single Nucleotide Polymorphisms with Age-Related Hearing
      Impairment in a Taiwanese Population.
AB  - OBJECTIVES: Age-related hearing impairment (ARHI) is a major disability among the
      elderly. This study aimed to analyze the association of single nucleotide
      polymorphisms (SNPs) of metabotropic glutamate receptor 7 (GRM7) gene with ARHI
      in an elderly population in Taiwan. MATERIALS AND METHODS: This was a community
      based study performed in a metropolitan hospital. Participants >=65 years of age
      were recruited. Participants with a pure tone average (PTA) of speech frequencies
      in the better ear of >35 decibel hearing level (dBHL) were classified into the
      case group, whereas those with PTA <=25 dBHL were classified into the control
      group. The association of SNPs rs11928865, rs1353828, rs9814809, and rs9880404
      with ARHI was analyzed. RESULTS: In 106 cases and 190 controls, alleles of all
      SNPs were found not to be associated with ARHI. The genotype of rs9880404 was
      found to be associated with ARHI in a dominant pattern, but the genotypes of
      rs11928865, rs1353828, and rs9814809 were found not to be associated with ARHI.
      CONCLUSION: GRM7 SNPs are associated with susceptibility to ARHI, but the
      significance of this finding in a Taiwanese population differed from that
      observed in European studies. Further studies may help to determine Taiwanese
      (Asian)-specific SNPs associated with ARHI.

PMID- 30100544
TI  - Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden
      Sensorineural Hearing Loss.
AB  - OBJECTIVES: The pathology of sudden sensorineural hearing loss, which is known as
      sudden deafness (SD), remains unknown. The purpose of this study was to
      investigate the association between mitochondrial uncoupling protein 2 (UCP2)
      polymorphism and SD risk. MATERIALS AND METHODS: We compared 83 patients
      suffering from SD and 2048 controls who participated in the Longitudinal Study of
      Aging at the National Institute for Longevity Sciences. Multiple logistic
      regression was used to calculate the odds ratios (ORs) for SD with a polymorphism
      of the UCP2 (rs660339) gene. RESULTS: Under the additive model of inheritance,
      UCP2 polymorphisms showed significant association with a SD risk. The OR was
      1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past
      history, such as diabetes, dyslipidemia, or hypertension, and for age and sex.
      CONCLUSION: Our results imply that the UCP2 (rs660339) polymorphism has a
      significant association with the risk of developing SD.

PMID- 30100545
TI  - Tricellulin Expression and its Deletion Effects in the Endolymphatic Sac.
AB  - OBJECTIVES: Tricellulin is a tight junction (TJ)-forming protein that
      participates in the sealing function of tricellular TJs. Tricellulin-knockout
      (Tric-/-) mice show progressive hearing loss with degeneration of hair cells in
      the cochlea without physiological or physical disorders. In the present study, we
      investigated the tricellulin expression and its deletion effects in the
      endolymphatic sac (ES) using Tric-/- mice. MATERIALS AND METHODS: The ES
      epithelia from wild-type (WT) mice were laser-microdissected, and RT-PCR was
      performed. The ES sections from Tric-/- and WT mice were immunostained with an
      anti-tricellulin antibody. Hematoxylin and eosin staining was performed for
      morphological examination. The inner ear of Tric-/- mice was perfused with
      biotinylation reagents, and the ES sections were observed for tracer permeability
      assay after applying streptavidin-Alexa Fluor 488 conjugate. RESULTS: The
      tricellulin expression was confirmed by RT-PCR and by immunohistochemistry in the
      WT ES. The ES in Tric-/- mice showed normal morphology and revealed no biotin
      leakage from the lumen. CONCLUSION: The ES in Tric-/- mice showed no changes in
      morphology or disruption in macromolecular barrier function. The effects of
      solute leakages in the ES of Tric-/- mice may be very limited and compensatable,
      or that the ES epithelia may have other sealing system covering the lack of
      tricellulin.

PMID- 30100546
TI  - Audiovestibular Loss of Function Correlates in Vestibular Schwannomas.
AB  - OBJECTIVES: The aim of the present study was to investigate the relationships
      between tumor size, hearing, and vestibular outcomes in patients with vestibular
      schwannomas (VSs). MATERIALS AND METHODS: Adult patients (n=124) with unilateral
      extrameatal VS prior to surgery were included in the study. This was a
      retrospective cohort study of preoperative audiovestibular investigations
      including audiometry, discrimination test, caloric test, cervical vestibular
      evoked myogenic potential (c-VEMP), and ocular vestibular evoked myogenic
      potential (o-VEMP). RESULTS: The difference between lesioned and non-lesioned ear
      was significant for all audiovestibular outcomes. The mean caloric deficit was
      74%. No tumor sided o-VEMPs were elicited. Caloric deficit correlated with
      hearing loss measured with pure tone average and discrimination score. c-VEMP
      deficit was significantly associated with severe hearing loss and larger tumors.
      CONCLUSION: The presence of VS leads to a significant deterioration of
      audiovestibular function in all objective measures. Caloric test and o-VEMPS are
      sensitive though unspecific measures of VSs. Increasing tumor size is not
      directly associated with hearing loss and only somewhat to vestibular deficit.
      However, audiovestibular findings are correlated.

PMID- 30100547
TI  - International Otology Outcome Group and the International Consensus on the
      Categorization of Tympanomastoid Surgery.
AB  - The International Otology Outcome Group (IOOG) was founded in 2017 to encourage
      and facilitate international collaboration with regard to the surgical outcome of
      ear surgery. This report outlines the methodology and recommendations of the
      consensus-based categorization of tympanomastoid surgery produced by the IOOG.
      The IOOG Steering Committee used the acronym SAMEO-ATO to categorize
      tympanomastoid operations, representing the stage of surgery, approach, mastoid
      bone extirpation, external bony wall repair, obliteration of the mastoid cavity,
      access to the middle ear, tympanic membrane reconstruction, and ossicular
      reconstruction. A modified Delphi technique was used to obtain international
      consensus. The expert panels included the chairpersons from 21 otology societies.
      The approval rate of the SAMEO-ATO system from the otology societies was 95%. The
      SAMEO-ATO scheme was presented at the 31st Politizer Meeting for field testing.
      There were no objections or serious concerns raised. Some international
      otologists wished to see more surgical categories included to reflect the
      varieties of surgical techniques, but they accepted that it would make the whole
      system cumbersome. In addition to providing an international categorization of
      tympanomastoid surgery, the IOOG Steering Committee plans to introduce a common
      otology dataset that the international otology community could use to record
      their surgical outcome. The high level of international consensus on the IOOG
      categorization of tympanomastoid surgery supports this tool for surgeons to pool
      their surgical data into a large database for research and comparative audit.

PMID- 30100548
TI  - Satisfaction with Life among Mothers of Pediatric Cochlear Implant Candidates:
      The Impact of Implant Operation and Sociodemographic Factors.
AB  - OBJECTIVES: To evaluate the satisfaction with life among mothers of pediatric
      cochlear implant candidates regarding implant surgery and sociodemographic
      factors. MATERIALS AND METHODS: Mothers of 160 pediatric patients with profound
      sensorineural hearing loss who underwent unilateral cochlear implant surgery were
      included. A questionnaire form with items on sociodemographic-familial
      characteristics and Satisfaction with Life Scale (SWLS) was employed via face-to
      face interview method before and 12 months after the implant surgery. RESULTS:
      The SWLS scores significantly improved after the implant surgery [from 19.1 (7.0)
      to 28.9 (4.0), p<0.000]. Being unemployed vs. employed [17.9 (6.9) vs. 24.0
      (5.3), p=0.000], having another child with hearing disability [13.5 (5.7) vs.
      19.7 (6.9), p=0.001], younger (12-24 months) vs. older (>24 months) age of the
      child at the time of implant surgery [7.1 (0.4) vs. 19.7 (6.6), p=0.001], absence
      vs. presence of regular follow-up visits [13.0 (0.0) vs. 19.4 (7.1), p=0.002],
      and presence vs. absence of change in social life after the diagnosis of disease
      [17.3 (6.5) vs. 20.9 (7.1), p=0.001] were associated with significantly lower
      SWLS scores among mothers. SWLS scores were positively correlated with patient's
      age at the time of implant surgery (r=0.206, p=0.009), whereas negatively
      correlated with the number of household members (r=-0.406, p=0.000) and number of
      children (r=-0.310, p=0.000). CONCLUSION: In conclusion, our findings revealed
      the association of cochlear implantation with a significant increase in mother's
      life satisfaction, despite the unemployment, presence of another child with
      hearing disability, and crowded household. Our findings emphasize on the
      consideration of family systems with special attention to mother's emotional
      experiences and occupational competence in the intervention programs.

PMID- 30100549
TI  - Renaming low risk conditions labelled as cancer.

PMID- 30100550
TI  - Multisensory bionic limb to achieve prosthesis embodiment and reduce distorted
      phantom limb perceptions.

PMID- 30100551
TI  - Surgery in patients with childhood-onset epilepsy: analysis of complications and
      predictive risk factors for a severely complicated course.
AB  - OBJECT: To compare the occurrence of surgery-related complications in patients
      with childhood-onset focal epilepsy operated on in the paediatric or in the adult
      age. To investigate risk factors for surgery-related complications in the whole
      cohort, with special attention to age at surgery and severe morbidity. METHODS: A
      cohort of 1282 patients operated on for childhood-onset focal epilepsy was
      retrospectively analysed. Occurrence of surgery-related complications, including
      a severely complicated course (SCC: surgical complication requiring reoperation
      and/or permanent neurological deficit and/or death), was compared between
      patients operated on in the paediatric age (<16 year-old; 452 cases) and,
      respectively, in adulthood (>=16 year-old; 830 cases). The whole cohort of
      patients was also evaluated for risk factors for a SCC. RESULTS: At last contact
      (median follow-up 98 months), 74.5% of patients were in Engel's class I (78.0% of
      children and 73.0% of adults). One hundred patients (7.8%) presented a SCC (6.4%
      for children and 8.6% for adult patients). Postoperative intracranial
      haemorrhages occurred more frequently in adult cases. At multivariate analysis,
      increasing age at operation, multilobar surgery, resections in the
      rolandic/perirolandic and in insulo-opercular regions were independent risk
      factors for a SCC. CONCLUSIONS: Surgery for childhood-onset focal epilepsy
      provides excellent results on seizures and an acceptable safety profile at any
      age. Nevertheless, our results suggest that increasing age at surgery is
      associated with an increase in odds of developing severe surgery-related
      complications. These findings support the recommendation that children with drug
      resistant, symptomatic (or presumed symptomatic) focal epilepsy should be
      referred for a surgical evaluation as early as possible after seizure onset.

PMID- 30100552
TI  - Performance of PML diagnostic criteria in natalizumab-associated PML: data from
      the Dutch-Belgian cohort.
AB  - OBJECTIVE: To test the current progressive multifocal leukoencephalopathy (PML)
      diagnostic criteria by applying them to patients previously diagnosed with
      natalizumab (NTZ)-associated PML in a real-world clinical setting. METHODS:
      Patients from the Dutch-Belgian NTZ-PML cohort (n=28) were reviewed at the time
      of first diagnostic work-up and during follow-up, using the PML diagnostic
      criteria as proposed in a consensus statement from the American Academy of
      Neurology. RESULTS: At first diagnostic work-up, 18 patients (64.3%) met the
      criteria for high diagnostic certainty for PML ('definite PML' or 'probable
      PML'). During follow-up, this increased to 20 patients (71.4%) as JC virus DNA
      was detected in cerebrospinal fluid of two additional patients. Nonetheless,
      28.6% of patients were still classified as 'possible PML' or 'not PML' (6 (21.5%)
      and 2 (7.1%) patients, respectively) despite a very high suspicion for PML based
      on lesion evolution and signs of PML-immune reconstitution inflammatory syndrome
      on MRI, and development of compatible symptoms. CONCLUSIONS: The current case
      definition of PML has low sensitivity for diagnosis of NTZ-PML in a real-world
      clinical setting in which MRI is frequently used for PML screening. This may
      delay diagnosis and appropriate management of PML, and may complicate a valid
      estimation of PML incidence during NTZ therapy.

PMID- 30100553
TI  - Glaucoma-associated long-term mortality in a rural cohort from India: the Andhra
      Pradesh Eye Disease Study.
AB  - AIM: To evaluate glaucoma-associated mortality in a rural cohort in India.
      METHODS: The study cohort comprised individuals aged 40 years and above who took
      part in the Andhra Pradesh Eye Disease Study (APEDS1) during 1996-2000. All
      participants underwent detailed comprehensive eye examination. Glaucoma was
      defined using International Society of Geographic and Epidemiologic Ophthalmology
      criteria. This cohort was followed up after a decade (June 2009 to January 2010;
      APEDS2). Mortality HR analysis for ocular risk factors was performed using Cox
      proportional hazards regression after adjusting for sociodemographic, lifestyle
      and clinical variables. RESULTS: In APEDS1, 2790 individuals aged more than or
      equal to 40 years were examined. 47.4% were male. Forty-five participants had
      primary open angle glaucoma (POAG) and 66 had primary angle closure disease
      (PACD). Ten years later, 1879 (67.3%) were available, 739 (26.5%) had died and
      172 (6.2%) had migrated; whereas 22 of the 45 (48.8%) with POAG and 22 of the 66
      (33.3%) with PACD had died. In univariate analysis, a higher mortality was
      associated with POAG (HR 1.9; 95% CI 1.23 to 2.94), pseudoexfoliation (HR 2.79;
      95% CI 2.0 to 3.89), myopia (HR 1.78; 95% CI 1.54 to 2.06) and unit increase in
      cup:disc ratio (HR 4.49; 95% CI 2.64 to 7.64). In multivariable analysis, only
      cup:disc ratio remained independently associated with mortality (HR 2.5; 95% CI
      1.3 to 5.1). The association remained significant when other ocular parameters
      were included in the model (HR 2.1; 95% CI 1.03 to 4.2). CONCLUSIONS: This is the
      first longitudinal study to assess the association of glaucoma and mortality in a
      rural longitudinal cohort in India. Increased cup:disc ratio could be a potential
      marker for ageing and would need further validation.

PMID- 30100554
TI  - Ultra-wide-field angiography findings in acute Vogt-Koyanagi-Harada disease.
AB  - BACKGROUND/AIMS: To investigate the prevalence of abnormal central and peripheral
      ultra-wide-field (UWF) angiography findings, and their association with clinical
      features in acute Vogt-Koyanagi-Harada (VKH) disease. METHODS: This
      retrospective, observational study included 26 eyes of 13 treatment-naive
      patients with acute VKH disease who underwent UWF fluorescein angiography (FA).
      Sixteen eyes of eight patients also underwent UWF indocyanine green angiography
      (ICGA). A circle simulating the central 75 degrees  field was used to divide the
      acquired image into the central fundus area (CFA) and peripheral fundus area
      (PFA), in which the presence of six previously reported abnormal angiographic
      findings were analysed. Correlations between abnormal angiography findings in FA
      and clinical features were also investigated. RESULTS: All eyes demonstrated more
      than one abnormal angiographic finding in both the CFA and PFA. UWF FA revealed
      three abnormal findings in the CFA versus the PFA: focal leakage (92.3% vs
      76.9%); pooling with a dark rim (84.6% vs 53.8%); and retinal vascular leakage
      (0% vs 46.2%). UWF ICGA revealed three abnormal findings in the CFA versus the
      PFA: hypofluorescent dark dots (100% vs 100%); diffusely leaking fuzzy choroidal
      vessels (93.8% vs 75.0%); and late hypofluorescent patches (81.3% vs 31.3%).
      Pooling with a dark rim and retinal vascular leakage in the PFA were
      significantly associated with low initial visual acuity (p=0.03) and subfoveal
      choroidal thickness change ratio (p=0.04), respectively. CONCLUSION: Abnormal UWF
      angiography findings were frequently detected in the CFA and PFA. Such findings
      may be useful in evaluation and monitoring of VKH disease.

PMID- 30100555
TI  - Microbiology and biofilm of corneal sutures.
AB  - AIM: To investigate the relationships between corneal suture bacteriology,
      biofilm and the clinical setting using culture studies and scanning electron
      microscopy (SEM). METHODS: This is a prospective, observational study of patients
      with a history of penetrating keratoplasty presenting to a tertiary cornea clinic
      for routine or symptoms-related corneal suture removal. We documented for each
      patient the suture clinical setting (quiescent, exposed and keratitis-related),
      retention time, antimicrobial therapy, bacterial growth on culture studies, and
      bacterial presence and biofilm coverage on SEM. RESULTS: There were significantly
      different culture positivity rates between the quiescent (8%), exposed (12%) and
      keratitis-related (60%) suture groups (p=0.039). As expected, keratitis-related
      sutures had the longest retention time compared with quiescent and exposed ones
      (p=0.02). The biofilm coverage score was higher for sutures from the keratitis
      related and exposed groups, although this trend was not statistically significant
      (p=0.90). Higher biofilm scores were seen in samples that also yielded a positive
      culture result (p=0.36) and in samples with bacterial presence on SEM images
      (p=0.16 and p=0.73). Both of these were important trends but not statistically
      significant. CONCLUSIONS: Evidence for active bacterial and biofilm presence on
      corneal sutures was found. Corneal sutures should be considered for removal
      sooner, before becoming exposed and/or keratitis-related. Traditional culture
      studies and SEM imaging are helpful in investigating biofilm and its clinical
      importance. More studies of the spectrum of bacterial growth on embedded
      biomedical devices such as corneal sutures are needed.

PMID- 30100556
TI  - Effect of optic disc-fovea distance on the normative classifications of macular
      inner retinal layers as assessed with OCT in healthy subjects.
AB  - PURPOSE: To determine the influence of the optic disc-fovea distance (DFD) on the
      normative classifications based on thickness measurements of macular inner
      retinal layers with spectral-domain optical coherence tomography (OCT) in healthy
      subjects. METHODS: A total of 182 eyes from 182 healthy subjects were included
      (mean (SD) spherical equivalent -0.8 (1.9) dioptres). We performed macula and
      optic disc imaging with the Topcon 3D OCT 2000. The thickness of the macular
      inner retinal layers (macular retinal nerve fibre layer (mRNFL), ganglion cell
      inner plexiform layer (GCIPL) and both combined (ganglion cell complex; GCC)) and
      the corresponding classifications based on the built-in normative database were
      recorded. The occurrence of an abnormal normative classification (occurrence of
      any thickness variable below the fifth percentile) was related to the DFD and
      other factors (axial length/refraction, optic disc area, fovea-disc angle, age,
      gender, image quality, visual field mean deviation and peripapillary retinal
      nerve fibre layer thickness), using logistic regression. RESULTS: The mean (SD)
      DFD was 4.90 (0.29) mm. A greater DFD was associated with a higher percentage of
      abnormal normative classification in the OCT parameters describing the thickness
      of the mRNFL (OR (95%CI) per 0.1 mm increase in DFD: 1.30 (1.13 to 1.50),
      p<0.001), GCIPL (1.18 (1.02 to 1.38), p=0.023) and GCC measurement (1.29 (1.08 to
      1.55), p=0.006). CONCLUSIONS: Eyes with a greater DFD are prone to false-positive
      classifications in the thickness assessment of the macular inner retinal layers.
      The thicknesses should always be interpreted in the context of DFD.

PMID- 30100557
TI  - Treatment of pediatric intracranial aneurysms: case series and meta-analysis.
AB  - BACKGROUND: There are limited outcome data to guide the choice of treatment in
      pediatric patients with cerebral aneurysms. OBJECTIVE: To describe our
      institutional experience treating pediatric patients with cerebral aneurysms and
      to conduct a meta-analysis of available studies to provide the best current
      evidence on treatment related outcomes. METHODS: We identified pediatric patients
      with cerebral aneurysms evaluated or treated at our institution using a
      comprehensive case log. We also identified studies to include in a meta-analysis
      through a systematic search of Pubmed, SCOPUS, EMBASE, and the Cochrane Database
      of Systematic Reviews. As part of both the local analysis and meta-analysis, we
      recorded patient characteristics, aneurysm characteristics, management, and
      outcomes. Statistical analysis was performed using Fisher's exact test and the
      two tailed Student's t test, as appropriate. RESULTS: 42 pediatric patients with
      57 aneurysms were evaluated at our institution, and treatment specific outcome
      data were available in 560 patients as part of our meta-analysis. Endovascular
      and surgical treatments yielded comparable rates of favorable outcome in all
      children (88.3% vs 82.7%, respectively, P=0.097), in children with ruptured
      aneurysms (75% vs 83%, respectively, P=0.357), and in children with unruptured
      aneurysms (96% vs 97%, respectively, P=1.000). CONCLUSION: Endovascular and
      surgical treatment yield comparable long term clinical outcomes in pediatric
      patients with cerebral aneurysms.

PMID- 30100558
TI  - The safety of triple antiplatelet therapy under thromboelastography guidance in
      patients undergoing stenting for ischemic cerebrovascular disease.
AB  - OBJECTIVE: To investigate the safety of triple antiplatelet therapy (TAT) with
      cilostazol in patients undergoing stenting for extracranial and/or intracranial
      artery stenosis. METHODS: A prospectively collected database was reviewed to
      identify patients who underwent stenting for extracranial and/or intracranial
      artery stenosis and showed resistance to aspirin and/or clopidogrel as assessed
      by pre-stenting thromboelastography (TEG) testing. Patients were assigned to a
      TAT group and a dual antiplatelet therapy (DAT) group. Major complications were
      defined as thromboembolic events (transient ischemic attack (TIA), ischemic
      stroke, and stent thrombosis) or major bleeding events within 30 days, and minor
      complications were defined as extracranial bleeding that did not require vascular
      surgery or transfusion within 30 days. RESULTS: A total of 183 patients were
      identified. The incidence of major complications was significantly lower in the
      TAT group than in the DAT group (TAT group vs. DAT group, 1/110 vs. 6/73;
      P=0.017). TIAs occurred in four patients, with one in the TAT group and three in
      the DAT group (1/110 vs. 3/73; P=0.303). Ischemic strokes occurred in three
      patients in the DAT group (TAT group vs. DAT group, P=0.062). No major bleeding
      events or stent thrombosis was recorded in either group. Two patients (one in
      each group) experienced minor complications that resolved without additional
      treatment (1/110 vs. 1/73; P>0.999). CONCLUSIONS: TAT under TEG guidance appears
      to be a safe antiplatelet strategy in patients undergoing stenting for
      extracranial and/or intracranial artery stenosis. By employing TAT under TEG
      guidance, favorable outcomes can be achieved in these patients.

PMID- 30100559
TI  - Response to: 'Role of tubulointerstitial injury in ANCA-associated vasculitis is
      underestimated' by Moiseev et al.

PMID- 30100560
TI  - Response to: 'Checkpoint inhibitors and arthritis: seeking balance between
      victories and defeats' by Moura and Moura.

PMID- 30100562
TI  - Cingulate gyrus epilepsy.
AB  - The cingulate gyrus is located above the corpus callosum and forms part of the
      limbic system. Cingulate gyrus epilepsy poses a diagnostic challenge, given its
      diverse and variable seizure semiology. We present two patients with seizures
      arising in the cingulate gyrus that highlight the electroclinical and imaging
      features of this rare form of epilepsy. Cingulate seizures can give a wide range
      of clinical manifestations, which relate to the underlying neuroanatomy and
      subdivisions of the cingulate cortex. Here, we review the semiology of cingulate
      epilepsy and how this relates to the location of seizure onset and patterns of
      propagation.

PMID- 30100561
TI  - Consensus proposal for taxonomy and definition of the autoinflammatory diseases
      (AIDs): a Delphi study.
AB  - Autoinflammatory diseases (AIDs) are a relatively new family of disorders,
      defined about 19 years ago. Some of them are hereditary and some are not. The
      names given to these diseases do not follow any systematic guidelines, and
      sometimes the same disorder carries several names. The aim of this study is to
      refine the definition of AIDs and to provide some conventions for their naming.
      We focused mainly on monogenetic AIDs. Delphi technique, which enables consensus
      among a group of experts through internet and mail communication and
      questionnaires, was employed. After achieving 100% consensus among six members of
      a steering committee, the questionnaire containing AID definitions and the agreed
      upon conventions were sent to 26 physicians and researchers working in the field
      of AIDs in order to gain broader support for the committee's proposals. The
      committee proposed the following definition for AIDs: "Autoinflammatory diseases
      are clinical disorders caused by defect(s) or dysregulation of the innate immune
      system, characterized by recurrent or continuous inflammation (elevated acute
      phase reactants-APR) and the lack of a primary pathogenic role for the adaptive
      immune system (autoreactive T-cells or autoantibody production)." Several rules
      were defined for guiding the naming of these diseases among which are: abandoning
      eponyms and preferring the name of the gene over its encoded protein. The new
      definition for AIDs allows inclusion of clinical disorders mainly associated with
      defects in the innate immune system. The new conventions propose names with
      clinical meaning and in some cases even clues for treatment.

PMID- 30100564
TI  - Michigan Appropriate Perioperative (MAP) criteria for urinary catheter use in
      common general and orthopaedic surgeries: results obtained using the RAND/UCLA
      Appropriateness Method.
AB  - BACKGROUND: Indwelling urinary catheters are commonly used for patients
      undergoing general and orthopaedic surgery. Despite infectious and non-infectious
      harms of urinary catheters, there is limited guidance available to surgery teams
      regarding appropriate perioperative catheter use. OBJECTIVE: Using the RAND
      Corporation/University of California Los Angeles (RAND/UCLA) Appropriateness
      Method, we assessed the appropriateness of indwelling urinary catheter placement
      and different timings of catheter removal for routine general and orthopaedic
      surgery procedures. METHODS: Two multidisciplinary panels consisting of 13 and 11
      members (physicians and nurses) for general and orthopaedic surgery,
      respectively, reviewed the available literature regarding the impact of different
      perioperative catheter use strategies. Using a standardised, multiround rating
      process, the panels independently rated clinical scenarios (91 general surgery,
      36 orthopaedic surgery) for urinary catheter placement and postoperative duration
      of use as appropriate (ie, benefits outweigh risks), inappropriate or of
      uncertain appropriateness. RESULTS: Appropriateness of catheter use varied by
      procedure, accounting for procedure-specific risks as well as expected procedure
      time and intravenous fluids. Procedural appropriateness ratings for catheters
      were summarised for clinical use into three groups: (1) can perform surgery
      without catheter; (2) use intraoperatively only, ideally remove before leaving
      the operating room; and (3) use intraoperatively and keep catheter until
      postoperative days 1-4. Specific recommendations were provided by procedure, with
      postoperative day 1 being appropriate for catheter removal for first voiding
      trial for many procedures. CONCLUSION: We defined the appropriateness of
      indwelling urinary catheter use during and after common general and orthopaedic
      surgical procedures. These ratings may help reduce catheter-associated
      complications for patients undergoing these procedures.

PMID- 30100563
TI  - Intestinal Metaproteomics Reveals Host-Microbiota Interactions in Subjects at
      Risk for Type 1 Diabetes.
AB  - OBJECTIVE: Dysbiosis of the gut microbiota has been linked to disease
      pathogenesis in type 1 diabetes, yet the functional consequences to the host of
      this dysbiosis are unknown. We investigated the functional interactions between
      the microbiota and the host associated with type 1 diabetes disease risk.
      RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of stool
      samples from subjects with recent-onset type 1 diabetes (n = 33), islet
      autoantibody-positive subjects (n = 17), low-risk autoantibody-negative subjects
      (n = 29), and healthy subjects (n = 22). Metaproteomic analysis was used to
      identify gut- and pancreas-derived host and microbial proteins, and these data
      were integrated with sequencing-based microbiota profiling. RESULTS: Both human
      (host-derived) proteins and microbial-derived proteins could be used to
      differentiate new-onset and islet autoantibody-positive subjects from low-risk
      subjects. Significant alterations were identified in the prevalence of host
      proteins associated with exocrine pancreas output, inflammation, and mucosal
      function. Integrative analysis showed that microbial taxa associated with host
      proteins involved in maintaining function of the mucous barrier, microvilli
      adhesion, and exocrine pancreas were depleted in patients with new-onset type 1
      diabetes. CONCLUSIONS: These data support that patients with type 1 diabetes have
      increased intestinal inflammation and decreased barrier function. They also
      confirmed that pancreatic exocrine dysfunction occurs in new-onset type 1
      diabetes and show for the first time that this dysfunction is present in high
      risk individuals before disease onset. The data identify a unique type 1 diabetes
      associated signature in stool that may be useful as a means to monitor disease
      progression or response to therapies aimed at restoring a healthy microbiota.

PMID- 30100565
TI  - The problem with composite indicators.
AB  - 'The Problem with...' series covers controversial topics related to efforts to
      improve healthcare quality, including widely recommended but deceptively
      difficult strategies for improvement and pervasive problems that seem to resist
      solution.

PMID- 30100566
TI  - Facilitators of interdepartmental quality improvement: a mixed-methods analysis
      of a collaborative to improve pediatric community-acquired pneumonia management.
AB  - BACKGROUND: Emergency medicine and paediatric hospital medicine physicians each
      provide a portion of the initial clinical care for the majority of hospitalised
      children in the USA. While these disciplines share goals to increase quality of
      care, there are scant data describing their collaboration. Our national,
      multihospital learning collaborative, which aimed to increase narrow-spectrum
      antibiotic prescribing for paediatric community-acquired pneumonia, provided an
      opportunity to examine factors influencing the success of quality improvement
      efforts across these two clinical departments. OBJECTIVE: To identify barriers to
      and facilitators of interdepartmental quality improvement implementation, with a
      particular focus on increasing narrow-spectrum antibiotic use in the emergency
      department and inpatient settings for children hospitalised with pneumonia.
      METHODS: We used a mixed-methods design, analysing interviews, written reports
      and quality measures. To describe hospital characteristics and quality measures,
      we calculated medians/IQRs for continuous variables, frequencies for categorical
      variables and Pearson correlation coefficients. We conducted in-depth,
      semistructured interviews by phone with collaborative site leaders; interviews
      were transcribed verbatim and, with progress reports, analysed using a general
      inductive approach. RESULTS: 47 US-based hospitals were included in this
      analysis. Qualitative analysis of 35 interview transcripts and 142 written
      reports yielded eight inter-related domains that facilitated successful
      interdepartmental quality improvement: (1) hospital leadership and support, (2)
      quality improvement champions, (3) evidence supporting the intervention, (4)
      national health system influences, (5) collaborative culture, (6) departments'
      structure and resources, (7) quality improvement implementation strategies and
      (8) interdepartmental relationships. CONCLUSIONS: The conceptual framework
      presented here may be used to identify hospitals' strengths and potential
      barriers to successful implementation of quality improvement efforts across
      clinical departments.

PMID- 30100567
TI  - Cardiac tamponade in a patient with ankylosing spondylitis: a notable response to
      TNF inhibitors.
AB  - Ankylosing spondylitis (AS) is a rheumatological disorder of the spine, and like
      many other rheumatological diseases, it can manifest as a systemic inflammation.
      We present a rare case of cardiac manifestations of AS in a 25-year-old man with
      recurrent chest pain and pericardial effusions. He initially presented with
      pleuritic chest pain, was diagnosed with cardiac tamponade and required emergent
      pericardiocentesis. The patient returned again with chest pain and was found to
      have reaccumulation of pericardial effusion. The cardiac symptoms were finally
      resolved when he was diagnosed and treated for AS.

PMID- 30100568
TI  - Isolated limb infusion as a treatment option for malignant granular cell tumour.
AB  - A 54-year-old man presented with a painful lesion on the right posterior calf
      with MRI identifying a 5 cm lesion in the medial head of the gastrocnemius. He
      underwent wide local excision of the tumour, and the final pathology was
      consistent with atypical granular cell tumour. Three years later, he developed a
      recurrent right popliteal mass. Complete staging workup also identified multiple
      lung nodules and a caecal polyp that were consistent with metastatic granular
      cell tumour. He was started on pazopanib and deemed a poor candidate for
      palliative resection due to encasement of the popliteal vessels. The patient
      refused above-the-knee amputation (AKA) at that point and was evaluated for
      isolated limb infusion as an alternative. He received three cycles of isolated
      limb infusion within a 2-year period and achieved good response from the first
      two cycles. He underwent AKA 4 years after his diagnosis of malignant granular
      cell tumours and is currently doing well.

PMID- 30100569
TI  - Levosulpiride-induced neuroleptic malignant syndrome in rheumatoid arthritis.
AB  - A 53-year-old woman, known case of diabetes mellitus and rheumatoid arthritis,
      presented with a 4-day history of hyperthermia, rigidity, tremor and altered
      sensorium. She developed these symptoms after having been administered parenteral
      levosulpiride to control vomiting due to secondary adrenal insufficiency. We
      managed her as a case of life-threatening neuroleptic malignant syndrome (NMS)
      requiring mechanical ventilation, bromocriptine and other supportive care. She
      subsequently recovered and was discharged in a stable condition. To the best of
      our knowledge, this is the first documented case report describing levosulpiride
      induced NMS.

PMID- 30100570
TI  - Paraneoplastic granulomatous dermatitis in a patient with Hodgkin's disease: a
      diagnostic pitfall.
AB  - The association of malignant lymphomas with non-necrotic epithelioid granulomas
      has been reported rarely since 1977. Hodgkin's disease-associated widespread
      cutaneous granuloma annulare (GA) has been reported in only eight patients. We
      report the second case of subcutaneous GA associated with Hodgkin's disease. A 73
      year-old man with Epstein-Barr virus-associated Hodgkin's lymphoma and
      paraneoplastic subcutaneous GA, presented 3 months after the diagnosis of
      malignancy. Examination revealed a large, broad erythematous, indurated,
      subcutaneous plaque spanning the majority of the left lower back and flank with
      no associated symptoms. Initial biopsy was suggestive of morphea. Prompted by
      positron emission tomography (PET) findings of increased fluorodeoxyglucose (FDG)
      uptake, a second, deeper biopsy was performed, revealing subcutaneous palisaded
      granulomatous dermatitis. After complete workup, the diagnosis most strongly
      suggested subcutaneous GA. This case highlights the importance of deep incisional
      biopsies, the fluorodeoxyglucose - positron emission tomography (FDG-PET)
      findings in GA and the rare association of GA with Hodgkin's disease which may
      signal the presence of malignancy.

PMID- 30100571
TI  - Acute lymphoblastic leukaemia with osteolytic bone lesions: diagnostic dilemma.
AB  - A previously healthy 37-year-old man presented with a 10-month history of
      intractable back pain. On examination, there was tenderness to palpation along
      lower thoracic and lumbar spine. Complete blood count showed mild anaemia but was
      otherwise unremarkable. Imaging studies revealed compression deformities with
      multiple osteolytic lesions involving multiple levels of the thoracic and lumbar
      spine. Bone marrow aspiration and biopsy were performed and demonstrated blast
      cells involving 80% of the bone marrow cellularity. Findings on flow cytometry
      were consistent with B-lymphoblastic leukaemia. He was subsequently started on
      hyper-CVAD (fractionated cyclophosphamide, vincristine, Adriamycin and
      dexamethasone) induction chemotherapy.

PMID- 30100572
TI  - Massively dilated common bile duct: an unusual aetiology for nutcracker
      phenomenon.

PMID- 30100573
TI  - Multidrug-resistant tuberculosis in rural China: lack of public awareness,
      unaffordable costs and poor clinical management.
AB  - China has the second highest global incidence and prevalence of multidrug
      resistant tuberculosis (MDR-TB). We describe here the life experience of a rural
      Chinese farmer with complicated and aggressive TB. It is unclear if this patient
      contracted MDR-TB initially or developed MDR-TB during treatment because the
      initial laboratory results are dubious. The lack of public awareness of TB in
      rural China fuelled by a belief in toxicity of TB treatment, as mentioned by his
      brother, caused the patient to stop his TB treatment repeatedly long before
      completion. The cost of MDR-TB treatment in China is unaffordable for most
      Chinese, especially those in rural areas. He paid about Y300 000 (almost US$50
      000) for his TB treatment. He was discharged early twice for 'financial
      difficulties'. This case highlights excessive costs, lack of public awareness,
      poor patient education, inadequate follow-up, lack of coordination between
      clinical services and the importance of treatment adherence.

PMID- 30100574
TI  - CT-derived muscle remodelling after bronchoscopic lung volume reduction in
      advanced emphysema.
AB  - : Muscle wasting frequently occurs in severe emphysema. Improving respiratory
      mechanics by bronchoscopic lung volume reduction using endobronchial valves (EBV)
      might prevent further loss or even increase in muscle mass. CT-derived skeletal
      muscle mass gain was observed in 39/49 patients 6 months after EBV. Multiple
      linear regression showed that gain in muscle (beta=2.4; 95% CI 0.2 to 4.6;
      p=0.036) and intramuscular fat (beta=3.1; 95% CI 0.2 to 5.9; p=0.035) is
      associated with improved 6 min walk distance independent of the change in
      residual volume. Skeletal muscle remodelling associates with improved exercise
      capacity after EBV, independent of hyperinflation reduction. TRIAL REGISTRATION
      NUMBER: Clinical trial registered with the Dutch trial register
      www.trialregister.nl (NTR2876), Results.

PMID- 30100575
TI  - FeNO monitoring to adjust treatment in asthma: has it come of age?

PMID- 30100576
TI  - Minimum important difference of the Epworth Sleepiness Scale in obstructive sleep
      apnoea: estimation from three randomised controlled trials.
AB  - BACKGROUND: The Epworth Sleepiness Scale (ESS) is a widely used tool for
      assessing sleepiness in patients with obstructive sleep apnoea (OSA). We aimed to
      estimate the minimal important difference (MID) in patients with OSA. METHODS: We
      used individual data from three randomised controlled trials (RCTs) in patients
      with OSA where the preintervention to postintervention change in ESS was used as
      a primary outcome. We used anchor-based linear regression and responder analysis
      approaches to estimate the MID. For anchors, we used the change in domains of the
      Functional Outcomes of Sleep Questionnaire and 36-Item Short Form Health Survey.
      We also used the distribution-based approaches Cohen's effect size, SE of
      measurement and empirical rule effect size to support the anchor-based estimates.
      The final MID was determined by triangulating all estimates to a single MID.
      FINDINGS: A total of 639 patients with OSA were included in our analyses across
      the three RCTs with a median (IQR) baseline ESS score of 10 (6-13). The median
      (IQR) ESS change score overall was -2 (-5 to 1). The anchor-based estimates of
      the MID were between -1.74 and -4.21 points and estimates from the responder
      analysis were between -1 and -3 points. Distribution-based estimates were
      smaller, ranging from -1.46 to -2.36. INTERPRETATION: We propose an MID for the
      ESS of 2 points in patients with OSA with a disease severity from mild to severe.
      This estimate provides the means to plan trials and interpret the clinical
      relevance of changes in ESS. TRIAL REGISTRATION NUMBER: Provent, NCT01332175;
      autoCPAP trial, NCT00280800; MOSAIC,ISRCTN (3416388).

PMID- 30100577
TI  - Association between age, deprivation and specific comorbid conditions and the
      receipt of major surgery in patients with non-small cell lung cancer in England:
      A population-based study.
AB  - INTRODUCTION: We investigated socioeconomic disparities and the role of the main
      prognostic factors in receiving major surgical treatment in patients with lung
      cancer in England. METHODS: Our study comprised 31 351 patients diagnosed with
      non-small cell lung cancer in England in 2012. Data from the national population
      based cancer registry were linked to Hospital Episode Statistics and National
      Lung Cancer Audit data to obtain information on stage, performance status and
      comorbidities, and to identify patients receiving major surgical treatment. To
      describe the association between prognostic factors and surgery, we performed two
      different analyses: one using multivariable logistic regression and one
      estimating cause-specific hazards for death and surgery. In both analyses, we
      used multiple imputation to deal with missing data. RESULTS: We showed strong
      evidence that the comorbidities 'congestive heart failure', 'cerebrovascular
      disease' and 'chronic obstructive pulmonary disease' reduced the receipt of
      surgery in early stage patients. We also observed gender differences and
      substantial age differences in the receipt of surgery. Despite accounting for
      sex, age at diagnosis, comorbidities, stage at diagnosis, performance status and
      indication of having had a PET-CT scan, the socioeconomic differences persisted
      in both analyses: more deprived people had lower odds and lower rates of
      receiving surgery in early stage lung cancer. DISCUSSION: Comorbidities play an
      important role in whether patients undergo surgery, but do not completely explain
      the socioeconomic difference observed in early stage patients. Future work
      investigating access to and distance from specialist hospitals, as well as
      patient perceptions and patient choice in receiving surgery, could help
      disentangle these persistent socioeconomic inequalities.

PMID- 30100578
TI  - Association of plasma vitamin C concentration to total and cause-specific
      mortality: a 16-year prospective study in China.
AB  - BACKGROUND: Vitamin C insufficiency occurs across many countries and has been
      hypothesised to increase risk of various diseases. Few prospective studies with
      measured circulating vitamin C have related deficiency to disease mortality,
      particularly in low-income and middle-income countries. METHODS: We randomly
      selected 948 subjects (473 males and 475 females) aged 53-84 years from a Chinese
      cohort and measured meta-phosphoric acid-preserved vitamin C concentrations in
      plasma samples collected in 1999-2000. A total of 551 deaths were accrued from
      sample collection through 2016, including 141 from cancer, 170 from stroke and
      174 from heart diseases. Vitamin C was analysed using season-specific quartiles,
      as a continuous variable and as a dichotomous variable based on sufficiency
      status (normal >28 umol/L vs low <=28 umol/L). HRs and 95% CIs were estimated
      using Cox proportional hazards models. RESULTS: We found significant inverse
      associations between higher plasma vitamin C concentrations and total mortality
      in quartile (HRQ4 vs Q10.75, 95% CI 0.59 to 0.95), continuous (HRq20umol/L0.90,
      95% CI 0.82 to 0.99) and dichotomous analyses (HRnormal-vs-low0.77, 95% CI 0.63
      to 0.95). We observed significant lower risks of heart disease (ptrend-by
      quantile=0.03) and cancer deaths (pglobal-across-quantile=0.04) for higher
      vitamin C, whereas the association was attenuated for stroke in adjusted models.
      Similar inverse associations were found when comparing normal versus low vitamin
      C for heart disease (HRnormal-vs-low0.62, 95% CI 0.42 to 0.89). CONCLUSION: In
      this long-term prospective Chinese cohort study, higher plasma vitamin C
      concentration was associated with lower total mortality, heart disease mortality
      and cancer mortality. Our results corroborate the importance of adequate vitamin
      C to human health.

PMID- 30100580
TI  - Genetic testing and counselling.

PMID- 30100579
TI  - Paternal age and the risk of low birth weight and preterm delivery: a Finnish
      register-based study.
AB  - BACKGROUND: Based on existing studies, there is no conclusive evidence as to
      whether and why paternal age matters for birth outcomes. METHODS: We used Finnish
      population registers on 106 652 children born 1987-2000. We first document the
      unadjusted association between paternal age and the risk of low birth weight
      (LBW; <2500 g) and preterm birth (<37 weeks' gestation). Second, we investigate
      whether the unadjusted association is attenuated on adjustment for child's,
      maternal and parental socioeconomic characteristics. Third, by adopting a within
      family design which involves comparing children born to the same father at
      different ages, we additionally adjust for unobserved parental characteristics
      shared between siblings. RESULTS: The unadjusted results show that being born to
      a father aged 40+, as opposed to a father aged 30-34, is associated with an
      increased risk of LBW of 0.96% (95% CI 0.5% to 1.3%) and to a younger father
      (<25) with a 1% (95% CI 0.6% to 1.3%) increased risk. The increased risk at
      younger paternal ages is halved on adjustment for the child's characteristics and
      fully attenuated on adjustment for child/parental characteristics. The increased
      risk at paternal ages 40+ is partially attenuated on adjustment for maternal
      characteristics (beta=0.62%; 95% CI 0.13% to 1.1%). Adjustment for unobserved
      parental characteristics shared by siblings further attenuates the 40+
      coefficient (beta=0.4%; 95% CI -0.5% to -1.2%). Results for preterm delivery are
      similar. CONCLUSIONS: The results underscore the importance of considering
      paternal age as a potential risk factor for adverse birth outcomes and of
      expanding research on its role and the mechanisms linking it to birth outcomes.

PMID- 30100582
TI  - Medical manslaughter.

PMID- 30100581
TI  - Somewhere between no-blame culture and treating medical errors as crimes.

PMID- 30100584
TI  - Joint recommendations on management of anaemia in patients with gastrointestinal
      bleeding in Hong Kong.
AB  - The demand for blood products continues to grow in an unsustainable manner in
      Hong Kong. While anaemia associated with gastrointestinal bleeding (GIB) is the
      leading indication for transfusion, there is no local recommendation regarding
      best practices for transfusion. We aimed to provide evidence-based
      recommendations regarding management of anaemia in patients with acute and
      chronic GIB. We reviewed all original papers, meta-analyses, systematic reviews,
      or guidelines that were available in PubMed. For acute GIB, a restrictive
      transfusion strategy, targeting a haemoglobin threshold of 7 to 8 g/dL, should be
      adopted because overtransfusion is associated with significantly higher all-cause
      mortality and re-bleeding. A liberal transfusion strategy should only be
      considered in patients with co-existing symptomatic coronary artery disease,
      targeting a haemoglobin threshold of 9 to 10 g/dL. When acute GIB settles,
      patients should be prescribed iron supplements if iron deficiency is present. For
      chronic GIB, iron stores should be replenished aggressively via iron
      supplementation before consideration of blood transfusion, except in patients
      with symptoms of severe anaemia. Oral iron replacement is the preferred first
      line therapy, while intravenous iron is indicated for patients with inflammatory
      bowel disease, poor response or poor tolerability to oral iron, and in whom a
      rapid correction of iron deficit is preferred. Intravenous iron is underutilised
      and the risk of anaphylactic reaction to current preparations is extremely low.
      These recommendations are provided to local clinicians to facilitate judicious
      and appropriate use of red cell products and iron replacement therapy in patients
      with GIB.

PMID- 30100583
TI  - Guidance on the management of familial hypercholesterolaemia in Hong Kong: an
      expert panel consensus viewpoin.
AB  - In 2016, meetings of groups of physicians and paediatricians with a special
      interest in lipid disorders and familial hypercholesterolaemia were held to
      discuss several domains of management of familial hypercholesterolaemia in adults
      and children in Hong Kong. After reviewing the evidence and guidelines for the
      diagnosis, screening, and management of familial hypercholesterolaemia, consensus
      was reached on the following aspects: clinical features, diagnostic criteria,
      screening in adults, screening in children, management in relation to target
      plasma low-density lipoprotein cholesterol levels, detection of atherosclerosis,
      lifestyle and behaviour modification, and pharmacotherapy.

PMID- 30100585
TI  - Chronic mucocutaneous candidiasis-more than just skin deep.

PMID- 30100586
TI  - Population-based mammography screening programme should be rigorously evaluated.

PMID- 30100587
TI  - Dextrose prolotherapy for improvement of rotator cuff lesions: ready for clinical
      use?

PMID- 30100588
TI  - Standing on the Shoulders of Giants: The Springboard for Creativity and Wisdom.

PMID- 30100589
TI  - Hundred Languages of Deaf Children: Exploring the Reggio Emilia Approach in Deaf
      Education.
AB  - The study investigated the "hundred languages of Deaf children" (Malaguzzi, 1993)
      in two schools using the Reggio Emilia approach to early childhood education,
      which originated in Italy. One principle of this approach, "the hundred languages
      of children," supports young children in expressing their ideas and thoughts in
      different ways. The hundred languages include expression through written, spoken,
      and signed languages, among many other means, and children are empowered to
      express themselves using these multiple channels. The researchers employed
      ethnographic study methods: Multiple early childhood classrooms were observed,
      and focus groups were conducted with school leaders, teachers, and families. The
      study findings are valuable in that they provide a better understanding of why
      both schools chose the Reggio Emilia approach with Deaf children and how both
      schools used it. Both schools regarded Deaf children as capable learners and
      expected much of them.

PMID- 30100590
TI  - Bedouin Hearing Parents of Children With Hearing Loss: Stress, Coping, and
      Quality of Life.
AB  - The authors examine parenting stress and coping strategies and their relation to
      satisfaction with family quality of life in a unique population: hearing Bedouin
      parents of children born with partial or total hearing loss in southern Israel.
      Could variables previously shown to predict families' quality of life in other
      populations with children with hearing loss also predict it in this underserved
      population? The study participants were 84 parents who responded to
      questionnaires. It was found that parenting stress affects satisfaction with the
      family's everyday functioning and that parents cope mainly by obtaining familial
      and social support and redefining the crisis situation. The latter strategy
      appears to improve the family's overall quality of life, whereas, surprisingly,
      cochlear implants do not. Thus, for such parents in traditional, marginalized
      societies, enhancing effective coping mechanisms may help reduce parenting stress
      and increase satisfaction with the family's quality of life.

PMID- 30100591
TI  - Service Providers' Perspective on the Education of Students Who Are Deaf or Hard
      of Hearing and English Learners.
AB  - The researchers examine the perspectives of service providers involved in
      educating students who are both deaf or hard of hearing (DHH) and English
      Learners (EL). Using qualitative phenomenology methodology, the researchers
      interviewed eight service providers in one school district about their
      perspectives on the unique challenges and issues related to educating students
      who are DHH EL. An overarching finding was the uniqueness of each individual
      student, which was found in the combination of factors, or "influencers of
      diversity" (Leigh, 2008, p. 25), for each student. The service providers reported
      that the students had unique communication, academic, and cultural needs beyond
      what one would expect to see only in EL or only in DHH learners. The results
      provide insights into service providers' challenges and needs and how they are
      met in the provision of effective services to DHH EL students.

PMID- 30100592
TI  - Nonsymbolic Comparison in Deaf Students: No Evidence for a Deficit in Numerosity
      Processing.
AB  - It is commonly found that deaf and hard of hearing (DHH) students experience
      delayed mathematical achievement. The present study used two nonsymbolic
      comparison tasks to explore the basic numerical skills of DHH students. Nine
      prelocutive DHH students with cochlear implants and nine hearing students,
      matched on nonverbal IQ, visual short-term memory, and verbal comprehension, were
      recruited. The participants performed two different collection comparison tasks
      with different ratios and under different perceptual conditions. Analyses by task
      showed similar response times, accuracy, and ratio effects for both groups on the
      Low Perceptual Condition task, a finding suggesting that the two groups accessed
      similar representations of quantity. Differences in performance on the simpler
      High Perceptual Condition task, on which the DHH group showed slower response
      times, probably were strategic in origin. The results suggest that DHH students
      have no deficits in basic numerical skills.

PMID- 30100593
TI  - Deaf or Hearing: A Hard of Hearing Individual's Navigation Between Two Worlds.
AB  - Identity construction and how an individual chooses to navigate or display his or
      her identity play an important role in how that person communicates and interacts
      with others. One group for whom identity construction and navigation is a
      difficult process is the hard of hearing population. In the present study,
      Communication Theory of Identity (Hecht, 1993) and interactive interviews were
      used to gain insight into four layers of identity-personal, relational, enacted,
      and communal-in the hard of hearing individual. The authors discuss the themes
      within each identity layer and the gaps that are present between layers, as well
      as the implications of the identified layers and gaps.

PMID- 30100594
TI  - Narrative Symposium: Patient and Research Participant experiences with Genetic
      Testing.
AB  - Twelve personal narratives address the challenges, benefits, and pitfalls of
      genetic testing. Three commentary articles explore these stories and suggest
      lessons that can be learned from them. The commentators come from backgrounds
      that include bioethics, public health, psychology, and philosophy.

PMID- 30100596
TI  - Editorial Note.

PMID- 30100597
TI  - If the Facts Were Not Untruths, Their Implications Were: Sponsorship Bias and
      Misleading Communication.
AB  - Sponsorship bias occurs when the financial interests of funders of scientific
      research influence claims made by scientists, especially in peer-reviewed
      publications. This article examines the relationship between sponsorship bias and
      misleading claims, understood as claims that are not necessarily false but which
      encourage those exposed to them to infer false conclusions. Misleading claims are
      relevant to how the term "bias" should be understood and thereby to evaluating a
      recent dispute about whether there is evidence of sponsorship bias in clinical
      research on statins. The concept of inferential asymmetry is introduced as an aid
      for understanding the relationship between misleading claims and sponsorship
      bias.

PMID- 30100598
TI  - Effective Reparation for the Guatemala S.T.D. Experiments: A Victim-Centered
      Approach.
AB  - Discussion of reparations for U.S.-Guatemala STD experiments of the 1940s and 50s
      should be informed by a range of international and U.S. reparation experiences,
      so that features that impair the effectiveness of repair are avoided, and
      features that enhance effectiveness of repair are emulated. Two features have
      contributed to the effectiveness or ineffectiveness of repair elsewhere but have
      not been critically examined in relation to the Guatemalan experiments: Whether
      experimental subjects or their families have the opportunity to participate in
      reparations processes, and whether any group of experimental subjects is
      intentionally denied recognition. Three advantages of victim participation are
      explored, and a critique provided of one narrow delimitation of victims. Even if
      political and moral failings ultimately prevent reparations for Guatemalan
      experimental subjects, an emphasis on effectiveness and victim-centeredness
      should nonetheless shape reparations for other, future victims of human rights
      abuses in experimentation.

PMID- 30100599
TI  - Reconceptualizing Autonomy for Bioethics.
AB  - Autonomy plays a central role in bioethics, but there is no consensus as to how
      we should understand this concept. This paper critically considers three
      different conceptions of autonomy: the default conception prevalent in bioethics
      literature; a broader procedural account of autonomy drawing on moral
      philosophical approaches; and a substantive, perfectionist account. Building on
      Rebecca Walker's critique of the default conception of autonomy, we will argue
      that a substantive, perfectionist approach both fulfils Walker's criteria for a
      conception of autonomy in bioethics and lends itself to application in practical
      scenarios. In so doing, we draw on scenarios from genomic medicine to show that a
      substantive, perfectionist approach not only offers a more conceptually adequate
      understanding of autonomy in more complex cases, but also lends itself to
      practical application by helping health professionals identify how they can
      maximize people's capacity to exercise their autonomy.

PMID- 30100600
TI  - She Touched Me: Five Snapshots of Adult Sexual Violations of Black Boys.
AB  - Too often the idea of young Black boys as sexually aggressive or criminally
      assaultive displaces the idea that they can be victims at all. As such, Black
      boys are not theorized or researched as victims of sexual violations in current
      gender literatures. Instead they are almost exclusively represented as
      perpetrators of sexual violence, not victims of it. This study examines five
      snapshots of Black men who were victims of sexual violations as young boys. Our
      findings indicate that Black males are uniquely at risk for sexual impropriety
      and statutory rape, primarily via older women and teenage girl female
      perpetrators (although risk also includes same-sex violations). This study, the
      first of its kind, argues that Black boys must be understood as a population at
      risk to be victims of sexual violations and require an earlier sex education
      emphasizing their sexual vulnerability.

PMID- 30100601
TI  - Are There Differences in the Management of Acute Pancreatitis Cases Due to Severe
      Hypertriglyceridemia in Pregnant Women?
AB  - BACKGROUND The aim of this study was to determine the prognosis of severe disease
      and treatment approaches of both normal and pregnant, especially in patients with
      severe pancreatitis due to hypertriglyceridemia. MATERIAL AND METHODS We included
      30 patients (20 females and 10 males) in this study whose follow-ups and
      treatments were performed after a diagnosis of hypertriglyceridemia-induced acute
      pancreatitis between January 2011 and May 2017. Patient personal information,
      such as age, sex, pre-treatment and post-treatment triglyceride levels, receipt
      of anti-hyperlipidemic treatments or plasmapheresis, and family history, were
      collected from hospital records and patient files. Patients with severe
      pancreatitis history, score, and prognosis were included to increase the value of
      our study. Mild and moderate cases were excluded. RESULTS The mean age of the
      patients was 35+/-6 years. Twenty-four patients (80%) received an anti
      hyperlipidemic treatment before their pancreatitis attacks. Plasmapheresis was
      performed on 8 patients before their pancreatitis attacks. Eighteen patients
      (60%) had a family history suggesting familial hypertriglyceridemia. Twelve
      patients (40%) were pregnant. CONCLUSIONS The treatment of hypertriglyceridemia
      induced acute pancreatitis was mostly confined to supportive, palliative
      treatments. However, plasmapheresis is a possible treatment option and should be
      used in the early stages of this disease. The response to medical treatment and
      support treatment was better in pregnant patients than in the other patient
      group, and pregnant patients did not require plasmapheresis.

PMID- 30100602
TI  - Multiple Myeloma in a Patient with Focal Segmental Glomerulosclerosis: A Case
      Report.
AB  - BACKGROUND Focal segmental glomerulosclerosis (FSGS) is a common cause of
      nephrotic syndrome in adults, which can be primary, or secondary to various
      causes. Unlike membranous nephropathy, FSGS is less likely to be associated with
      malignancy. Few cases have been reported of the occurrence of FSGS with
      hematological malignancies like multiple myeloma (MM). CASE REPORT A 48-year-old
      man presented with nephrotic syndrome and renal impairment and was diagnosed with
      primary FSGS after kidney biopsy, which showed a segmental scar with diffuse
      effacement of foot processes on electron microscopy. Treatment with steroids
      reduced proteinuria and stabilized the renal function. A few months later, the
      patient presented with acute Kidney Injury, bone pain, and anemia. A diagnosis of
      MM was made based on the bone marrow biopsy. Treatment of MM decreased
      proteinuria and improved renal function. CONCLUSIONS There is an association
      between FSGS and MM through an unclear mechanism.

PMID- 30100603
TI  - [Validity and reliability of the self-efficacy to regulate exercise scale in
      patients with metabolic syndrome].
AB  - OBJECTIVE: Self-efficacy refers to beliefs in individuals' own capacities to do
      something. With the intent of evaluate the validity and reliability, we
      investigated the psychometric properties of the Self-Efficacy to Regulate
      Exercise Scale (SERES) in patients with metabolic syndrome (MetS). METHODS: 135
      participants with medical diagnosis of MetS took part in the study (Mage=55.5,
      SD=7.6). We investigated sociodemographic, psychological, and life-style
      variables. Participants were recruited at the Hospital Universitario Virgen de
      las Nieves (HUVN) in Granada (Spain) between 2013 and 2014. In order to
      characterise the sample, descriptive statistics were used. Factorial analysis,
      internal consistency and convergent reliability of the SERES were also
      calculated. Group differences were investigated using Student's t test. RESULTS:
      A solution with two factors was extracted, which explained 72.7% of the variance
      of the SERES. The internal consistency values for the total score of the SERES
      were (0.925 and 0.864) according to the values of Cronbach's alpha and Guttman's
      two halves, respectively. Significant correlations of the SERES were detected for
      with physical exercise, assertiveness, stress, anger, and active life-style
      (e.g., renouncing to sedentary behaviours). CONCLUSIONS: This was the first study
      to report on psychometric properties of the SERES. Results supported the adequacy
      of the measure for use with patients with MetS. SERES seemed to be useful in
      evaluating self-efficacy in relation to physical exercise, psychosocial, and
      lifestyle variables.

PMID- 30100604
TI  - [Analysis of proton pump inhibitors anti-ulcer drugs use in the Araba district
      primary care area].
AB  - OBJECTIVE: The proton pump inhibitors (PPI) anti-ulcer drugs are one of the most
      prescribed pharmacological groups in primary care. The objective of the work was
      to know the prescription of PPI in a Primary Care Area, the Araba district of the
      Basque Health Service, to advise family doctors about its correct use, and
      encourage the prescription of the most efficient PPIs. METHODS: Descriptive study
      of 200 family doctors PPI prescription at the Araba district of the Basque Health
      Service. Data were obtained from prescriptions billed by pharmacies between 2009
      and 2014. We analyzed the expenses and DHD (DDD per 1000 inhabitants/day) of PPIs
      dispensed and the omeprazole relative uptake compared to other PPIs. Statistical
      analysis was performed with IBM SPSS v23(r) statistic software. RESULTS: IBP
      prescription increased by 23.75% (from 78.14 DHD in 2009 to 96.70 DHD in 2014).
      Their use was much higher than that of other European countries. In the same
      period, omeprazole relative prescription compared to other PPIs decreased by
      4.56% (omeprazole % Defined daily dose (DDD) went from 74.67% in 2009 to 70.11%
      in 2014). The overall expenditure of these medicines decreased by 17.60%.
      CONCLUSIONS: There is an overall increase in the prescription of PPIs, although
      the expenses have decreased due to price drop. Likewise there is a decrease in
      the relative consumption of omeprazole, although the indications approved had not
      changed. PPIs prescription should be done with caution since their unjustified
      high use in the prevention of gastropathy increases the risk of inappropriate
      prescriptions. The most recommended PPI continues to be omeprazole.

PMID- 30100606
TI  - Gut mechanosensors: enterochromaffin cells feel the force via PIEZO2.

PMID- 30100607
TI  - Increasing the bactofection capacity of a mammalian expression vector by removal
      of the f1 ori.
AB  - Bacterial-mediated cancer therapy has shown great promise in in vivo tumour
      models with increased survival rates post-bacterial treatment. Improving
      efficiency of bacterial-mediated tumour regression has focused on controlling and
      exacerbating bacterial cytotoxicity towards tumours. One mechanism that has been
      used to carry this out is the process of bactofection where post-invasion,
      bacteria deliver plasmid-borne mammalian genes into target cells for expression.
      Here we utilised the cancer-targeting Salmonella Typhimurium strain, SL7207, to
      carry out bactofection into triple negative breast cancer MDA-MB-231 cells.
      However, we noted that post-transformation with the commonly used mammalian
      expression vector pEGFP, S. Typhimurium became filamentous, attenuated and unable
      to invade target cells efficiently. Filamentation did not occur in Escherichia
      coli-transformed with the same plasmid. Further investigation identified the
      region inducing S. Typhimurium filamentation as being the f1 origin of
      replication (f1 ori), an artefact of historic use of mammalian plasmids for
      single stranded DNA production. Other f1 ori-containing plasmids also induced the
      attenuated phenotype, while removal of the f1 ori from pEGFP restored S.
      Typhimurium virulence and increased the bactofection capacity. This work has
      implications for interpretation of prior bactofection studies employing f1 ori
      containing plasmids in S. Typhimurium, while also indicating that future use of
      S. Typhimurium in targeting tumours should avoid the use of these plasmids.

PMID- 30100609
TI  - Glucagon-like peptide-1 receptor (GLP-1R) signaling in the ventral hippocampus
      reduces feeding via monosynaptic communication to the medial prefrontal cortex
      (mPFC).

PMID- 30100605
TI  - Notch3 inhibits epithelial-mesenchymal transition in breast cancer via a novel
      mechanism, upregulation of GATA-3 expression.
AB  - Notch3 and GATA binding protein 3 (GATA-3) have been, individually, shown to
      maintain luminal phenotype and inhibit epithelial-mesenchymal transition (EMT) in
      breast cancers. In the present study, we report that Notch3 expression positively
      correlates with that of GATA-3, and both are associated with estrogen receptor
      alpha (ERalpha) expression in breast cancer cells. We demonstrate in vitro and in
      vivo that Notch3 suppressed EMT and breast cancer metastasis by activating GATA-3
      transcription. Furthermore, Notch3 knockdown downregulated GATA-3 and promoted
      EMT; while overexpression of Notch3 intracellular domain upregulated GATA-3 and
      inhibited EMT, leading to a suppression of metastasis in vivo. Moreover,
      inhibition or overexpression of GATA-3 partially reversed EMT or mesenchymal
      epithelial transition induced by Notch3 alterations. In breast cancer patients,
      high GATA-3 expression is associated with higher Notch3 expression and lower
      lymph node metastasis, especially for hormone receptor (HR) positive cancers.
      Herein, we demonstrate a novel mechanism whereby Notch3 inhibit EMT by
      transcriptionally upregulating GATA-3 expression, at least in part, leading to
      the suppression of cancer metastasis in breast cancers. Our findings expand our
      current knowledge on Notch3 and GATA-3's roles in breast cancer metastasis.

PMID- 30100610
TI  - Genomic sequencing in acutely ill infants: what will it take to demonstrate
      clinical value?

PMID- 30100608
TI  - Tracking microevolution events among ST11 carbapenemase-producing hypervirulent
      Klebsiella pneumoniae outbreak strains.
AB  - The recent convergence of genetic elements encoding phenotypic carbapenem
      resistance and hypervirulence within a single Klebsiella pneumoniae host strain
      represents a major public concern. To obtain a better understanding of the
      genetic characteristic of this emerging 'superbug', the complete genomes of 3
      isolates of ST11 carbapenemase-producing hypervirulent K. pneumoniae were
      generated using the Oxford nanopore MinION platform. Comparative whole-genome
      analysis identified 13 SNPs and 3 major regions of indels in the chromosomes of
      the clonally disseminated isolates. ISKpn18-mediated disruption in the mgrB gene,
      which was associated with colistin resistance, was identified in two later
      strains, leading to the emergence of hypervirulent K. pneumoniae that was
      simultaneously colistin- and carbapenem-resistant. Five plasmids were recovered
      from each isolate, including a 178 Kb IncHI1B/FIB-type rmpA2-bearing virulence
      plasmid, a 177.5 Kb IncFII/R self-transferable blaKPC-2-bearing MDR plasmid, a
      99.7 Kb Incl1 plasmid and two ColRNAI-type plasmids of sizes of 11.9 and 5.6 Kb,
      respectively. The presence of homologous regions between the non-conjugative
      virulence plasmid and conjugative blaKPC-2-bearing MDR plasmid suggests that
      transmission of the virulence plasmid from ST23 K. pneumoniae to ST11 CRKP may be
      mediated by the co-integrated transfer of these two plasmids. Emergence of
      colistin-resistant and carbapenemase-producing hypervirulent K. pneumoniae
      strains further emphasizes the urgency for the establishment of a coordinated
      global program to eradicate hypervirulent and/or pan-drug-resistant strains of K.
      pneumoniae from clinical settings and the community.

PMID- 30100611
TI  - Discovery of new susceptibility genes: proceed cautiously.

PMID- 30100612
TI  - Including ELSI research questions in newborn screening pilot studies.
AB  - BACKGROUND: The evidence review processes for adding new conditions to state
      newborn screening (NBS) panels rely on data from pilot studies aimed at assessing
      the potential benefits and harms of screening. However, the consideration of
      ethical, legal, and social implications (ELSI) of screening within this research
      has been limited. This paper outlines important ELSI issues related to newborn
      screening policy and practices as a resource to help researchers integrate ELSI
      into NBS pilot studies. APPROACH: Members of the Bioethics and Legal Workgroup
      for the Newborn Screening Translational Research Network facilitated a series of
      professional and public discussions aimed at engaging NBS stakeholders to
      identify important existing and emerging ELSI challenges accompanying NBS.
      RESULTS: Through these engagement activities, we identified a set of key ELSI
      questions related to (1) the types of results parents may receive through newborn
      screening and (2) the initiation and implementation of NBS for a condition within
      the NBS system. CONCLUSION: Integrating ELSI questions into pilot studies will
      help NBS programs to better understand the potential impact of screening for a
      new condition on newborns and families, and make crucial policy decisions aimed
      at maximized benefits and mitigating the potential negative medical or social
      implications of screening.

PMID- 30100613
TI  - Development of an evidence-based algorithm that optimizes sensitivity and
      specificity in ES-based diagnostics of a clinically heterogeneous patient
      population.
AB  - PURPOSE: Next-generation sequencing (NGS) is rapidly replacing Sanger sequencing
      in genetic diagnostics. Sensitivity and specificity of NGS approaches are not
      well-defined, but can be estimated from applying NGS and Sanger sequencing in
      parallel. Utilizing this strategy, we aimed at optimizing exome sequencing (ES)
      based diagnostics of a clinically diverse patient population. METHODS:
      Consecutive DNA samples from unrelated patients with suspected genetic disease
      were exome-sequenced; comparatively nonstringent criteria were applied in variant
      calling. One thousand forty-eight variants in genes compatible with the clinical
      diagnosis were followed up by Sanger sequencing. Based on a set of variant
      specific features, predictors for true positives and true negatives were
      developed. RESULTS: Sanger sequencing confirmed 81.9% of ES-derived variants.
      Calls from the lower end of stringency accounted for the majority of the false
      positives, but also contained ~5% of the true positives. A predictor
      incorporating three variant-specific features classified 91.7% of variants with
      100% specificity and 99.75% sensitivity. Confirmation status of the remaining
      variants (8.3%) was not predictable. CONCLUSIONS: Criteria for variant calling in
      ES-based diagnostics impact on specificity and sensitivity. Confirmatory
      sequencing for a proportion of variants, therefore, remains a necessity. Our
      study exemplifies how these variants can be defined on an empirical basis.

PMID- 30100614
TI  - Otx2 promotes granule cell precursor proliferation and Shh-dependent
      medulloblastoma maintenance in vivo.
AB  - The developmental gene OTX2 is expressed by cerebellar granule cell precursors
      (GCPs), a cell population which undergoes massive expansion during the early
      postnatal period in response to sonic hedgehog (Shh). GCPs are thought to be at
      the origin of most medulloblastomas, a devastating paediatric cancer that arises
      in the developing cerebellum. OTX2 is overexpressed in all types of
      medulloblastomas, except in Shh-dependent type 2 medulloblastomas, although it
      has GCPs as cell-of-origin. This has led to the current view that OTX2 is not
      involved in tumorigenesis of this subgroup. How OTX2 might contribute to normal
      or tumoral GCP development in vivo remains unresolved. Here, we have
      investigated, for the first time, the physiological function of this factor in
      regulating proliferation and tumorigenesis in the developing mouse cerebellum. We
      first characterized Otx2-expressing cells in the early postnatal cerebellum and
      showed that they represent a unique subpopulation of highly proliferative GCPs.
      We next performed in vivo loss-of-function analysis to dissect out the role of
      Otx2 in these cells and identified a novel, Shh-independent, function for this
      factor in controlling postnatal GCP proliferation and cerebellum morphogenesis.
      Finally, we addressed the function of Otx2 in the context of type 2
      medulloblastomas by directing Shh-dependent tumour formation in Otx2+ cells of
      the developing cerebellum and assessing the effects of Otx2 ablation in this
      context. We unravel an unexpected, mandatory function for Otx2 in sustaining cell
      proliferation and long-term maintenance of these tumours in vivo, therefore
      bringing unpredicted insight into the mechanisms of type 2 medulloblastoma
      subsistence. Together, these data pinpoint, for the first time, a crucial Shh
      independent role for Otx2 in the control of proliferation of normal and tumoral
      granule cell precursors in vivo and make it an attractive candidate for targeted
      therapy in Shh-dependent medulloblastomas.

PMID- 30100615
TI  - An African-specific profile of pharmacogene variants for rosuvastatin plasma
      variability: limited role for SLCO1B1 c.521T>C and ABCG2 c.421A>C.
AB  - Studies in Caucasian and Asian populations consistently associated
      interindividual and interethnic variability in rosuvastatin pharmacokinetics to
      the polymorphisms SLCO1B1 c.521T>C (rs4149056 p. Val174Ala) and ABCG2 c.421C>A
      (rs2231142, p. Gln141Lys). To investigate the pharmacogenetics of rosuvastatin in
      African populations, we first screened 785 individuals from nine ethnic African
      populations for the SLCO1B1 c.521C and ABCG2 c.421CA variants. This was followed
      by sequencing whole exomes from individuals of African Bantu descent, who
      participated in a 20 mg rosuvastatin pharmacokinetic trial in Harare Zimbabwe.
      Frequencies of SLCO1B1 c.521C ranged from 0.0% (San) to 7.0% (Maasai), while
      ABCG2 c.421A ranged from 0.0% (Shona) to 5.0% (Kikuyu). Variants showing
      significant association with rosuvastatin exposure were identified in SLCO1B1,
      ABCC2, SLC10A2, ABCB11, AHR, HNF4A, RXRA and FOXA3, and appear to be African
      specific. Interindividual differences in the pharmacokinetics of rosuvastatin in
      this African cohort cannot be explained by the polymorphisms SLCO1B1 c.521T>C and
      ABCG2 c.421C>A, but appear driven by a different set of variants.

PMID- 30100616
TI  - Fine-mapping analysis of a chromosome 2 region linked to resistance to
      Mycobacterium tuberculosis infection in Uganda reveals potential regulatory
      variants.
AB  - Tuberculosis (TB) is a major public health burden worldwide, and more effective
      treatment is sorely needed. Consequently, uncovering causes of resistance to
      Mycobacterium tuberculosis (Mtb) infection is of special importance for vaccine
      design. Resistance to Mtb infection can be defined by a persistently negative
      tuberculin skin test (PTST-) despite living in close and sustained exposure to an
      active TB case. While susceptibility to Mtb is, in part, genetically determined,
      relatively little work has been done to uncover genetic factors underlying
      resistance to Mtb infection. We examined a region on chromosome 2q previously
      implicated in our genomewide linkage scan by a targeted, high-density association
      scan for genetic variants enhancing PTST- in two independent Ugandan TB household
      cohorts (n = 747 and 471). We found association with SNPs in neighboring genes
      ZEB2 and GTDC1 (peak meta p = 1.9 * 10-5) supported by both samples.
      Bioinformatic analysis suggests these variants may affect PTST- by regulating the
      histone deacetylase (HDAC) pathway, supporting previous results from
      transcriptomic analyses. An apparent protective effect of PTST- against body-mass
      wasting suggests a link between resistance to Mtb infection and healthy body
      composition. Our results provide insight into how humans may escape latent Mtb
      infection despite heavy exposure.

PMID- 30100617
TI  - A DNA barcoding method for identifying and quantifying the composition of pollen
      species collected by European honeybees, Apis mellifera (Hymenoptera: Apidae).
AB  - The European honeybee, Apis mellifera L. (Hymenoptera: Apidae), is the most
      important crop pollinator, and there is an urgent need for a sustained supply of
      honeybee colonies. Understanding the availability of pollen resources around
      apiaries throughout the brood-rearing season is crucial to increasing the number
      of colonies. However, detailed information on the floral resources used by
      honeybees is limited due to a scarcity of efficient methods for identifying
      pollen species composition. Therefore, we developed a DNA barcoding method for
      identifying the species of each pollen pellet and for quantifying the species
      composition by summing the weights of the pellets for each species. To establish
      the molecular biological protocol, we analyzed 1008 pellets collected between
      late July and early September 2016 from five hives placed in a
      forest/agricultural landscape of Hokkaido, northern Japan. Pollen was classified
      into 31 plant taxa, of which 29 were identified with satisfactory discrimination
      (25 species and 4 genera) using trnL-trnF and ITS2 as DNA barcoding regions
      together with available floral and phenological information. The remaining two
      taxa were classified to the species level using other DNA barcoding regions. Of
      the 1008 pollen pellets tested, 1005 (99.7%) were successfully identified. As an
      example of the use of this method, we demonstrated the change in species
      composition of pollen pellets collected each week for 9 weeks from the same hive.

PMID- 30100618
TI  - Adaptive physiological and biochemical response of sugarcane genotypes to high
      temperature stress.
AB  - Impact of elevated temperature on physiological and biochemical changes were
      evaluated in 5 commercial sugarcane genotypes and 2 wild species clones at two
      different growth phases. The study revealed that heat stress decreased
      chlorophyll content, chlorophyll stability index (CSI), SPAD value, maximum
      quantum efficiency of PSII photochemistry (Fv/Fm ratio), leaf gas exchange
      parameters, relative water content (RWC), and activities of nitrate reductase
      (NR), sucrose-metabolizing enzymes (SPS, SS, AI, NI) in all the genotypes and
      species clones. In contrast, elevated temperature induced an increase in proline,
      total phenolics content (TP), antioxidant enzyme activities (SOD and POX), lipid
      peroxidation (LP), membrane injury index (MII) and soluble sugar content in all
      clones. Principal component analysis based on physiological heat tolerance
      indexes could clearly distinguish sugarcane genotypes into three heat tolerance
      clusters. Noteworthy in comparison to the heat-sensitive varieties, sugarcane
      genotype that possessed higher degrees of heat tolerance Co 99004 displayed
      higher chlorophyll content, CSI, antioxidant enzyme activities, NR activity, RWC,
      total phenols, sucrose-metabolizing enzymes, soluble sugar content and leaf gas
      exchange and lower level of lipid peroxidation and membrane injury index.

PMID- 30100620
TI  - Psychological, Relational, and Emotional Effects of Self-Disclosure After
      Conversations With a Chatbot.
AB  - Disclosing personal information to another person has beneficial emotional,
      relational, and psychological outcomes. When disclosers believe they are
      interacting with a computer instead of another person, such as a chatbot that can
      simulate human-to-human conversation, outcomes may be undermined, enhanced, or
      equivalent. Our experiment examined downstream effects after emotional versus
      factual disclosures in conversations with a supposed chatbot or person. The
      effects of emotional disclosure were equivalent whether participants thought they
      were disclosing to a chatbot or to a person. This study advances current
      understanding of disclosure and whether its impact is altered by technology,
      providing support for media equivalency as a primary mechanism for the
      consequences of disclosing to a chatbot.

PMID- 30100621
TI  - Emotion-Focused Therapy for Autism Spectrum Disorder: A Case Conceptualization
      Model for Trauma-Related Experiences.
AB  - People with autism spectrum disorder (ASD) report painful experiences through
      emotional misunderstandings with typically developing peers. There are limited
      intervention methodologies for ASD on the impact of emotional injuries and how to
      work with resulting trauma. This paper presents a rational-empirical model of
      trauma-related experiences with the first presentation of a new case
      conceptualization model for emotion-focused therapy for ASD. It describes the
      transformation of problematic emotion schemes through a sequence of emotional
      processing steps illustrated with a case example. These steps include: overcoming
      differentiation of core painful feelings (such as loneliness, shame, and fear);
      autobiographical memory recall of distanced trauma, using a novel method of video
      Interpersonal Process Recall; and articulation of the unmet needs contained in
      core painful feelings. This is followed by the expression of an emotional
      response to those feelings/needs; typically, self-soothing, protective anger and
      compassion responses offered interpersonally by group members. These emerging
      adaptive emotions facilitate mentalization of self and other that strengthens
      intrapersonal and interpersonal agency. This rational-empirical case
      conceptualization acts as a hypothesis for testing in subsequent trials.

PMID- 30100619
TI  - The gut microbiome is associated with behavioural task in honey bees.
AB  - The gut microbiome is recognised as playing an integral role in the health and
      ecology of a wide variety of animal taxa. However, the relationship between
      social behavioural traits and the microbial community has received little
      attention. Honey bees are highly social and the workers perform different
      behavioural tasks in the colony that cause them to be exposed to different local
      environments. Here we examined whether the gut microbial community composition of
      worker honey bees is associated with the behavioural tasks they perform, and
      therefore also the local environment they are exposed to. We set up five
      observation hives, in which all workers were matched in age and observed the
      behaviour of marked bees in each colony over 4 days. The gut bacterial
      communities of bees seen performing predominantly foraging or predominantly in
      nest tasks were then characterised and compared based on amplicon sequencing of
      the 16S rRNA gene. Our results show that some core members of the unique honey
      bee gut bacterial community are represented in different relative abundances in
      bees performing different behavioural tasks. The differentially represented
      bacterial taxa include some thought to be important in carbohydrate metabolism
      and transport, and also linked to bee health. The results suggest an influence of
      task-related local environment exposure and diet on the honey bee gut microbial
      community and identify focal core taxa for further functional analyses.

PMID- 30100622
TI  - Got Milk? How Freedoms Evolved From Dairying Climates.
AB  - The roots and routes of cultural evolution are still a mystery. Here, we aim to
      lift a corner of that veil by illuminating the deep origins of encultured
      freedoms, which evolved through centuries-long processes of learning to pursue
      and transmit values and practices oriented toward autonomous individual choice.
      Analyzing a multitude of data sources, we unravel for 108 Old World countries a
      sequence of cultural evolution reaching from (a) ancient climates suitable for
      dairy farming to (b) lactose tolerance at the eve of the colonial era to (c)
      resources that empowered people in the early industrial era to (d) encultured
      freedoms today. Historically, lactose tolerance peaks under two contrasting
      conditions: cold winters and cool summers with steady rain versus hot summers and
      warm winters with extensive dry periods (Study 1). However, only the cold/wet
      variant of these two conditions links lactose tolerance at the eve of the
      colonial era to empowering resources in early industrial times, and to encultured
      freedoms today (Study 2). We interpret these findings as a form of gene-culture
      coevolution within a novel thermo-hydraulic theory of freedoms.

PMID- 30100623
TI  - Satellite observations and modeling to understand the Lower Mekong River basin
      streamflow variability.
AB  - In this work, we have used the Soil & Water Assessment Tool (SWAT) to examine
      streamflow variability of the Lower Mekong River Basin (LMRB) associated with
      changes in the Upper Mekong River Basin (UMRB) inflows. Two hypothetical
      experiments were formulated and evaluated for the LMRB, where we conducted runoff
      simulations with multiple inflow changes that include upstream runoff yield
      increase and decrease scenarios. Streamflow variability of the LMRB was
      quantified by two streamflow metrics that explain flow variability and
      predictability, and high flow disturbance. The model experiments were performed
      for the Lower Mekong River Basin with identical climate, soil, and other
      watershed characteristics data. Remote sensing precipitation (Tropical Rainfall
      Measurement Mission, TRMM, and Global Precipitation Measurement mission, GPM),
      meteorological data as well as spatial data that include a digital elevation
      model, newly developed soil information (Harmonized World Soil Database, HWSD),
      and land use and land cover were processed as input to the LMRB model
      simulations. Observed daily streamflow data along the Lower Mekong River from
      Chiang Sean, Thailand to Kratie, Cambodia were used for calibration and
      validation. Our work results suggest that the Lower Mekong River streamflow is
      highly variable and has a low predictability (Colwell index of about 32%). We
      found that releasing more water from upstream Mekong during rainfall months by
      30% would result in a reduction in the Lower Mekong streamflow predictability by
      about 21%. This reduction in predictability is mainly attributed to a decrease in
      the Contingency index. Our work shows that the ability to predict floods/droughts
      at the Lower Mekong River would be reduced if there is any anticipated change
      (i.e., increase/decrease) from UMRB releases. Our results also show that
      releasing more flows from the upstream Mekong would also affect flood duration
      and the frequency of flood occurrences downstream. The results of this work thus
      help to quantify the sensitivity of streamflow variability at the Lower Mekong
      River Basin to upstream anthropogenic changes.

PMID- 30100625
TI  - On Sahlqvist Formulas in Relevant Logic.
AB  - This paper defines a Sahlqvist fragment for relevant logic and establishes that
      each class of frames in the Routley-Meyer semantics which is definable by a
      Sahlqvist formula is also elementary, that is, it coincides with the class of
      structures satisfying a given first order property calculable by a Sahlqvist-van
      Benthem algorithm. Furthermore, we show that some classes of Routley-Meyer frames
      definable by a relevant formula are not elementary.

PMID- 30100624
TI  - Intergenerational Support and the Emotional Well-being of Older Jews and Arabs in
      Israel.
AB  - This investigation examined the cultural context of intergenerational support
      among older Jewish and Arab parents living in Israel. The authors hypothesized
      that support from adult children would be more positively consequential for the
      psychological well-being of Arab parents than of Jewish parents. The data derived
      from 375 adults age 65 and older living in Israel. Psychological well-being was
      measured with positive and negative affect subscales of the Positive and Negative
      Affect Schedule. Overall, positive affect was highest when filial expectations
      for support were congruent with whether or not instrumental support was received.
      Findings by cultural background revealed that, among older Jews, receiving
      instrumental support raised positive affect and stronger filial expectations
      lowered it. Among older Arabs, receiving financial support raised positive affect
      and receiving instrumental support lowered it. Culture appears to serve as a
      potent force in determining which types of intergenerational support functions
      are expected and accepted means of serving the everyday needs of older parents.

PMID- 30100626
TI  - Does Limiting Allowable Rating Variation in the Small Group Health Insurance
      Market Affect Employer Self-Insurance?
AB  - The Affordable Care Act (ACA) imposes adjusted community rating in the small
      group market, which employers can avoid by self-insuring, raising concerns about
      adverse selection. We evaluate the impact of limiting allowable rating variation
      on employer self-insurance across industries with varied health risk, using cross
      state variation in pre-ACA rating regulations, the nationally-representative 2008
      2013 KFF/HRET Employer Health Benefits survey, and a triple-difference regression
      approach. We find that lower-risk employers subject to laws limiting allowable
      premium rating variation have a predicted probability of self-insurance that is
      about 18 percentage points higher than otherwise-similar higher-risk employers,
      suggesting that these selection concerns are warranted.

PMID- 30100628
TI  - Review: the energetic value of zooplankton and nekton species of the Southern
      Ocean.
AB  - Understanding the energy flux through food webs is important for estimating the
      capacity of marine ecosystems to support stocks of living resources. The energy
      density of species involved in trophic energy transfer has been measured in a
      large number of small studies, scattered over a 40-year publication record. Here,
      we reviewed energy density records of Southern Ocean zooplankton, nekton and
      several benthic taxa, including previously unpublished data. Comparing measured
      taxa, energy densities were highest in myctophid fishes (ranging from 17.1 to
      39.3 kJ g-1 DW), intermediate in crustaceans (7.1 to 25.3 kJ g-1 DW), squid (16.2
      to 24.0 kJ g-1 DW) and other fish families (14.8 to 29.9 kJ g-1 DW), and lowest
      in jelly fish (10.8 to 18.0 kJ g-1 DW), polychaetes (9.2 to 14.2 kJ g-1 DW) and
      chaetognaths (5.0-11.7 kJ g-1 DW). Data reveals differences in energy density
      within and between species related to size, age and other life cycle parameters.
      Important taxa in Antarctic food webs, such as copepods, squid and small
      euphausiids, remain under-sampled. The variability in energy density of Electrona
      antarctica was likely regional rather than seasonal, although for many species
      with limited data it remains difficult to disentangle regional and seasonal
      variability. Models are provided to estimate energy density more quickly using a
      species' physical parameters. It will become increasingly important to close
      knowledge gaps to improve the ability of bioenergetic and food web models to
      predict changes in the capacity of Antarctic ecosystems to support marine life.

PMID- 30100627
TI  - Oceanographic barriers to gene flow promote genetic subdivision of the tunicate
      Ciona intestinalis in a North Sea archipelago.
AB  - Pelagic larval development has the potential to connect populations over large
      geographic distances and prevent genetic structuring. The solitary tunicate Ciona
      intestinalis has pelagic eggs and a swimming larval stage lasting for maximum a
      few days, with the potential for a homogenizing gene flow over relatively large
      areas. In the eastern North Sea, it is found in a geomorphologically complex
      archipelago with a mix of fjords and open costal habitats. Here, the coastal
      waters are also stratified with a marked pycnocline driven by salinity and
      temperature differences between shallow and deep waters. We investigated the
      genetic structure of C. intestinalis in this area and compared it with
      oceanographic barriers to dispersal that would potentially reduce connectivity
      among local populations. Genetic data from 240 individuals, sampled in 2 shallow,
      and 4 deep-water sites, showed varying degrees of differentiation among samples
      (FST = 0.0-0.11). We found no evidence for genetic isolation by distance, but two
      distant deep-water sites from the open coast were genetically very similar
      indicating a potential for long-distance gene flow. However, samples from
      different depths from the same areas were clearly differentiated, and fjord
      samples were different from open-coast sites. A biophysical model estimating
      multi-generation, stepping-stone larval connectivity, and empirical data on fjord
      water mass retention time showed the presence of oceanographic barriers that
      explained the genetic structure observed. We conclude that the local pattern of
      oceanographic connectivity will impact on the genetic structure of C.
      intestinalis in this region.

PMID- 30100629
TI  - Solution-based low-temperature synthesis of germanium nanorods and nanowires.
AB  - Abstract: The Ga-assisted formation of Ge nanorods and nanowires in solution has
      been demonstrated and a catalytic activity of the Ga seeds was observed. The
      synthesis of anisotropic single-crystalline Ge nanostructures was achieved at
      temperatures as low as 170  degrees C. Gallium not only serves as nucleation seed
      but is also incorporated in the Ge nanowires in higher concentrations than its
      thermodynamic solubility limit. Graphical abstract: 

PMID- 30100630
TI  - Umbelliferone instability during an analysis involving its extraction process.
AB  - Abstract: Umbelliferone (7-hydroxycoumarin) is one of the most popular compounds
      of the coumarins family. This compound receives the attention of scientists due
      to its diverse bioactivities in a number of applications in various therapeutic
      fields. An interesting aspect of umbelliferone is its structural lability. The
      enzymatic degradation process of umbelliferone to its hydroxylated (esculetin),
      glucosylated (skimmin), and methylated (herniarin) derivatives is already known
      from the literature. In this paper, we describe the possibility of umbelliferone
      transformation to other derivatives. We found that eight compounds were formed
      from umbelliferone during its simulated extraction under reflux performed in
      different conditions (different heating times and solvents used). Six of them
      (4,7-dihydroxy-3,4-dihydro-2H-chromen-2-one, 3,7-dihydroxy-3,4-dihydro-2H-chromen
      2-one, methyl (2E)-3-(2,4-dihydroxyphenyl)prop-2-enoate, ethyl (2E)-3-(2,4
      dihydroxyphenyl)prop-2-enoate, (2E)-3-[2-(acetyloxy)-4-hydroxyphenyl]prop-2-enoic
      acid, (2E)-3-(2-amino-4-hydroxyphenyl)prop-2-enoic acid) have not been reported
      yet. Some of these compounds were also identified in extracts of plant materials
      containing umbelliferone-chamomile flower and cinnamon bark. Compound separation
      was carried out using the HPLC apparatus. All compounds were identified based on
      their MS fragmentation paths. The presented results are useful for food producers
      and consumers, as umbelliferone transformation products can be formed during food
      product storage, their preparation or processing. Graphical abstract: 

PMID- 30100631
TI  - Adsorption of adenine on mercury electrode in acetate buffer at pH 5 and pH 6 and
      its effect on electroreduction of zinc ions.
AB  - Abstract: The measurements of double-layer differential capacitance, zero charge
      potential, and surface tension at that potential allowed us to examine the
      adsorption properties of adenine on the mercury surface from the neat buffer
      solution, i.e., the acetate buffer at pH 5 and pH 6. The systems obtained at such
      pH values were close to physiological fluids in their characteristics. The
      adsorption energy and interaction constants were determined using Frumkin
      isotherm and virial isotherm. It was shown that the adenine molecule is adsorbed
      on the mercury electrode with its negative pole against the electrode surface.
      Using the cyclic voltammetry technique and measuring Faraday impedance, an
      increasing effect of adenine on the kinetics of zinc ion electroreduction was
      found. In both buffer solutions, the neutral adenine molecules can form on the
      surface of the working electrode, an unstable active complex with depolarizer
      ions, facilitating electron exchange. Graphical abstract: 

PMID- 30100634
TI  - Explicit upper bound for the average number of divisors of irreducible quadratic
      polynomials.
AB  - Consider the divisor sum ?n<=Ntau(n2+2bn+c) for integers b and c. We extract an
      asymptotic formula for the average divisor sum in a convenient form, and provide
      an explicit upper bound for this sum with the correct main term. As an
      application we give an improvement of the maximal possible number of D(-1) 
      quadruples.

PMID- 30100633
TI  - Synthesis and evaluation of new amidrazone-derived hydrazides as a potential anti
      inflammatory agents.
AB  - Abstract: The series of new hydrazide derivatives were synthesized in reactions
      of N3-substituted amidrazones with cyclic anhydrides as potential anti
      inflammatory and antibacterial agents. The compounds were characterized by 1H-13C
      two-dimensional NMR techniques, which revealed the presence of two tautomeric
      forms in DMSO-d6 solutions, while the molecular structure of one species was
      confirmed by single-crystal X-ray diffraction. The anti-inflammatory effects of
      hydrazides on peripheral blood mononuclear cells were experimentally evaluated.
      Three compounds showed antiproliferative activity comparable to ibuprofen. One
      derivative demonstrated strong reduction of lymphocyte proliferation stimulated
      by anti-CD3 antibody (by 90%) and PHA, as well as low cell toxicity. The obtained
      compounds exhibited relatively weak antibacterial activity; they were more
      effective against Gram-positive bacterial strains. Graphical abstract: 

PMID- 30100635
TI  - An optimal adaptive wavelet method for first order system least squares.
AB  - In this paper, it is shown that any well-posed 2nd order PDE can be reformulated
      as a well-posed first order least squares system. This system will be solved by
      an adaptive wavelet solver in optimal computational complexity. The applications
      that are considered are second order elliptic PDEs with general inhomogeneous
      boundary conditions, and the stationary Navier-Stokes equations.

PMID- 30100632
TI  - Synthesis of unsymmetrical disulfanes bearing 1,2,4-triazine scaffold and their
      in vitro screening towards anti-breast cancer activity.
AB  - Abstract: A new series of 1,2,4-triazine unsymmetrical disulfanes were prepared
      and evaluated as anticancer activity compounds against MCF-7 human breast cancer
      cells with some of them acting as low micromolar inhibitors. Evaluation of the
      cytotoxicity using an MTT assay, the inhibition of [3H]-thymidine incorporation
      into DNA demonstrated that these products exhibit cytotoxic effects on breast
      cancer cells in vitro. The most effective compounds with 59 and 60 uM compared to
      chlorambucil with 47 uM were disulfanes bearing methyl and methoxy substituent in
      an aromatic ring. Furthermore, all new 14 compounds were obtained with 22-74%
      yield via mild and efficient synthesis of the sulfur-sulfur bond formation from
      thiols and symmetrical disulfanes using 2,3-dichloro-5,6-dicyanobenzoquinone
      (DDQ). The molecular structure of the newly obtained compounds was confirmed by X
      ray analysis. The conformational preferences of disulfide system were
      characterized using theoretical calculations at DFT level and statistical
      distributions of C-S-S-C torsion angle values based on the Cambridge Structural
      Database (CSD). The DFT calculations and CSD searching show two preferential
      conformations for C-S-S-C torsion angle close to +/- 90 degrees  and relatively
      large freedom of rotation on S-S bond in physiological conditions. The molecular
      docking studies were performed using the human estrogen receptor alpha (ERalpha)
      as molecular target to find possible binding orientation and intermolecular
      interactions of investigated disulfanes within the active site of ERalpha. The
      S...H-S and S...H-C hydrogen bonds between sulfur atoms of bisulfide bridge and S
      H and C-H groups of Cys530 and Ala350 as protein residues play crucial role in
      interaction with estrogen receptor for the most anticancer active disulfane.
      Graphical abstract: 

PMID- 30100636
TI  - Representing the Good: Pastoral Care in a Secular Age.
AB  - In 'a secular age' (Taylor 2007), pastoral care is no longer exclusively
      associated with specific religious traditions and communities. Pastoral
      caregivers who work in secular institutions provide care to religious and
      nonreligious people alike, and in several Western societies the term pastoral
      care is used in relation to nonreligious (humanist) care. In secular contexts,
      the term 'pastoral care' is often replaced by the term 'spiritual care.'
      Spiritual care, however, is provided by various professionals, so pastoral
      caregivers face the challenge of developing adequate and convincing language to
      explain what is distinctive about their work. In this article, the authors turn
      to philosophical language in order to develop a conceptual understanding of
      pastoral care that does not depend on the specific worldview-religious or
      nonreligious-of either pastoral caregivers or receivers of pastoral care. Using
      the work of Taylor (1989, 2007) and Murdoch (1970), we explain pastoral care as
      engaging with people's attempts to orient in 'moral space' and the distinctive
      quality of pastoral care as 'representing the Good.' Murdoch associates 'the
      Good' with a secular idea of transcendence that is both a movement beyond the ego
      and an engagement with the reality of human vulnerability, suffering, and evil.
      We argue that pastoral caregivers who 'represent the Good' have the task not only
      of supporting the existential and spiritual processes of individuals but also of
      promoting dialogue and social justice and of critiquing dehumanizing practices in
      the organizations in which they work and in society at large.

PMID- 30100637
TI  - Quasi-Experimental Designs for Causal Inference.
AB  - When randomized experiments are infeasible, quasi-experimental designs can be
      exploited to evaluate causal treatment effects. The strongest quasi-experimental
      designs for causal inference are regression discontinuity designs, instrumental
      variable designs, matching and propensity score designs, and comparative
      interrupted time series designs. This article introduces for each design the
      basic rationale, discusses the assumptions required for identifying a causal
      effect, outlines methods for estimating the effect, and highlights potential
      validity threats and strategies for dealing with them. Causal estimands and
      identification results are formalized with the potential outcomes notations of
      the Rubin causal model.

PMID- 30100638
TI  - VISUAL FEEDBACK ARRAY TO ACHIEVE REPRODUCIBLE LIMB DISPLACEMENTS AND VELOCITIES
      IN HUMANS.
AB  - Precise and reproducible feedback is important for studies on motor control, the
      adaptive responses to exercise training and the limits of human neuromuscular
      performance. For this purpose, a custom instrumentation array was previously
      developed to provide human subjects with visual feedback on their contractile
      durations and limb velocities during knee extension exercise. The array consisted
      of two columns, each with 14 high-visibility light emitting diodes. One array
      column provided the subject with the target cadence of position change while the
      complementary array provided an indication of the actual rate of displacement
      achieved by the subject. The array design has been improved to include an onboard
      microcontroller-based signal generator to generate the desired protocol cadence
      and also the ability to easily customize and 'lock in' desired protocol
      parameters. The array allows for custom settings to provide feedback on the
      concentric and eccentric activation periods during exercise. It can also be used
      in clinical settings to track the active or passive ranges of motion during
      rehabilitation.

PMID- 30100639
TI  - Trauma Focused Cognitive Behavioral Therapy with Children of Incarcerated
      Parents.
AB  - This paper explores children's trauma symptoms related to parental incarceration
      and lays the groundwork for the implementation of Trauma Focused Cognitive
      Behavioral Therapy (TF-CBT) within a clinical community-based setting treating
      children and adolescents affected by parental incarceration. Children and
      adolescents who experience parental incarceration are more likely to develop
      symptoms of post-traumatic stress disorder (PTSD): depression, anger, aggression,
      and isolating and self-harming behaviors. Although parental incarceration is a
      known source of trauma, there are no documented studies examining effective
      clinical treatments to reduce the effects of the trauma experienced by these
      children and adolescents. Except for children and adolescents affected by
      parental incarceration, TF-CBT, a promising model for treating and reducing the
      symptoms of PTSD, has been successfully applied to various populations affected
      by trauma. Children of incarcerated parents resemble populations treated with TF
      CBT in earlier applications. In this paper, we present a case illustration that
      examines the application of TF-CBT with one child who experienced trauma symptoms
      related to parental incarceration, while discussing the results of that
      application and the potential for broader applicability of TF-CBT within
      community-based organizations that treat the population of children and families
      affected by parental incarceration.

PMID- 30100640
TI  - Autism Spectrum Disorder: The Impact of Stressful and Traumatic Life Events and
      Implications for Clinical Practice.
AB  - Research findings suggest that behavioral interventions are effective in
      improving educational outcomes and fostering skill development in people with
      autism spectrum disorder (ASD). However, high rates of comorbidity between ASD
      and other psychological disorders, including depression and anxiety, indicate
      that standard behavioral approaches are not adequately addressing issues related
      to mental health in this population. Research emerging since the publication of
      the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders
      (DSM-5) is advancing our understanding of the nature of childhood stress and
      trauma in people with ASD and its subsequent impact on mental health and
      wellbeing. Mounting evidence for stress and trauma as a risk factor for
      comorbidity and the worsening of core ASD symptoms may intimate a shift in the
      way clinical social workers and other clinical practitioners conceptualize and
      approach work with this population to include trauma-focused assessment
      strategies and clinical interventions. Future directions for research to better
      understand the nature of childhood stress and trauma and improve mental health in
      this population are also discussed.

PMID- 30100641
TI  - Remission from Depression in the DSM: Moving from Rhetoric to Restoration.
AB  - The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, the most
      recent edition of the Diagnostic and Statistical Manual of Mental Disorders, uses
      the term "remission" to describe the reduction of depressive symptoms. This paper
      argues that by categorizing someone who no longer has depressive symptoms as "in
      remission," that person may feel indefinitely tied to his or her diagnosis.
      Considering the unfortunate stigma associated with mental illness, permanent
      linkage to diagnosis through records and professional memory may cause
      individuals to internalize pathology. In fact, the language of the diagnosis can
      affect self-perception in sensitive souls for a lifetime. As an implication for
      practice, we propose that cognitive and narrative therapy approaches, mood
      memoirs, and use of metaphor present alternative uses of language that can reduce
      power imbalances between clinicians and clients, providing a bridge to healing.

PMID- 30100642
TI  - Transforming Satellite Data into Weather Forecasts.
AB  - Teaser: A NASA project spans the gap between research and operations, introducing
      new composites of satellite imagery to weather forecasters to prepare for the
      next generation of satellites.

PMID- 30100644
TI  - Pistis as Relational Way of Life in Galatians.
AB  - Using the Septuagint as an example, this article supports Teresa Morgan's recent
      contention that piiotasigmatauiotasigma is essentially relational. On the basis
      of the prevalence of relationality, the article offers a critique of readings of
      Galatians that privilege other concepts, such as Benjamin Schliesser's emphasis
      on spatiality. The study then argues that, instead of Morgan's 'pistis is a
      relationship', it would be more accurate and exegetically useful to bring out the
      action-reference of piiotasigmatauiotasigma with an expression such as
      'piiotasigmatauiotasigma is a relational way of life'. The article will argue
      that the most likely relational reading of piiotasigmatauiotasigma in Galatians
      is one in which piiotasigmatauiotasigma primarily represents trust, loyalty
      and/or trustworthiness in the relationship between the current Christ and people.
      This raises questions over the focus of piiotasigmatauiotasigma on past events in
      the work of scholars such as Richard Hays and John Barclay. If
      piiotasigmatauiotasigma Chirhoiotasigmatauomicron? is to be read as involving an
      'objective genitive' it probably denotes people's trust in and loyalty to Christ
      and also possibly to God through Christ. If it is to be read as a 'subjective
      genitive', it would probably primarily denote Christ's current reliability and
      loyalty in his relationship to people, and conceivably also to God. Various
      directions of piiotasigmatauiotasigma between people, Christ and God are possible
      in Galatians but the one most often clearly evidenced is between people and
      Christ.

PMID- 30100643
TI  - Elemental distribution in developing rice grains and the effect of flag-leaf
      arsenate exposure.
AB  - We measured the bulk grain concentrations of arsenic (As), along with rubidium
      (Rb) and strontium (Sr) as indicators of phloem and xylem transport respectively,
      in rice (Oryza sativa cv. Italica Carolina) pulsed with arsenate at two exposure
      levels for 5 day periods at progressively later stages of grain fill, between
      anthesis and maturity, through the cut flag leaf. We compared these to unexposed
      (negative) controls and positive controls; pulsed with dimethylarsinic acid
      (DMA). We collected elemental maps of As and micronutrient elements (Fe, Zn, Mn,
      Cu and Ni) from developing grains of rice. Exposures were either 25 or 100 MUg/ml
      arsenate (As(V)) at various stages of grain development, compared to 25 MUg/ml
      dimethylarsinic acid (DMA); the most efficiently transported As species
      identified in rice. We used the spatial distribution of arsenic in the grain to
      infer the presence of As transporters. By exposing grains through the flag leaf
      rather than via the roots, we were able to measure arsenic transport into the
      grain during filling under controlled conditions. Exposure to 100 MUg/ml As(V)
      resulted in widespread As localization in both embryo and endosperm, especially
      in grains exposed to As at later stages of panicle development. This suggests
      loss of selective transport, likely to be the result of As toxicity. At 25 MUg/ml
      As(V), As colocalized with Mn in the ovular vascular trace (OVT). Exposure to
      either As(V) or DMA reduced grain Fe, an effect more pronounced when exposure
      occurred earlier in grain development. The abundance of Cu and Zn were also
      reduced by As. Arsenic exposure later in grain development caused higher grain As
      concentrations, indicating the existence of As transporters whose efficiency
      increases during grain fill. We conclude that localization of As in the grain is
      a product of both As species and exposure concentration, and that high As(V)
      translocation from the flag leaf can result in high As concentrations in the
      endosperm.

PMID- 30100645
TI  - Intelligence in youth and health behaviours in middle age.
AB  - Objective: We investigated the association between intelligence in youth and a
      range of health-related behaviours in middle age. Method: Participants were the
      5347 men and women who responded to the National Longitudinal Survey of Youth
      1979 (NLSY-79) 2012 survey. IQ was recorded with the Armed Forces Qualification
      Test (AFQT) when participants were aged 15 to 23 years of age. Self-reports on
      exercise (moderate activity, vigorous activity, and strength training), dietary,
      smoking, drinking, and oral health behaviours were recorded when participants
      were in middle age (mean age = 51.7 years). A series of regression analyses
      tested for an association between IQ in youth and the different health related
      behaviours in middle age, while adjusting for childhood socio-economic status
      (SES) and adult SES. Results: Higher IQ in youth was significantly associated
      with the following behaviours that are beneficial to health: being more likely to
      be able to do moderate cardiovascular activity (Odds Ratio, 95% CI) (1.72, 1.35
      to 2.20, p < .001) and strength training (1.61, 1.37 to 1.90, p < .001); being
      less likely to have had a sugary drink in the previous week (0.75, 0.71 to 0.80,
      p < .001); a lower likelihood of drinking alcohol heavily (0.67, 0.61 to 0.74, p
      < .001); being less likely to smoke (0.60, 0.56 to 0.65, p < .001); being more
      likely to floss (1.47, 1.35 to 1.59, p < .001); and being more likely to say they
      "often" read the nutritional information (1.20, 1.09 to 1.31, p < .001) and
      ingredients (1.24, 1.12 to 1.36, p < .001) on food packaging compared to always
      reading them. Higher IQ was also linked with dietary behaviours that may or may
      not be linked with poorer health outcomes (i.e. being more likely to have skipped
      a meal (1.10, 1.03 to 1.17, p = .005) and snacked between meals (1.37, 1.26 to
      1.50, p < .001) in the previous week). An inverted u-shaped association was also
      found between IQ and the number of meals skipped per week. Higher IQ was also
      linked with behaviours that are known to be linked with poorer health (i.e. a
      higher likelihood of drinking alcohol compared to being abstinent from drinking
      alcohol (1.58, 1.47 to 1.69, p < .001)). A u-shaped association was found between
      IQ and the amount of alcohol consumed per week and an inverted u-shaped
      association was found between IQ and the number of cigarettes smoked a day.
      Across all outcomes, adjusting for childhood SES tended to attenuate the
      estimated effect size only slightly. Adjusting for adult SES led to more marked
      attenuation but statistical significance was maintained in most cases.
      Conclusion: In the present study, a higher IQ in adolescence was associated with
      a number of healthier behaviours in middle age. In contrast to these results, a
      few associations were also identified between higher intelligence and behaviours
      that may or may not be linked with poor health (i.e. skipping meals and snacking
      between meals) and with behaviours that are known to be linked with poor health
      (i.e. drinking alcohol and the number of cigarettes smoked). To explore
      mechanisms of association, future studies could test for a range of health
      behaviours as potential mediators between IQ and morbidity or mortality in later
      life.

PMID- 30100647
TI  - A neurocomputational model of developmental trajectories of gifted children under
      a polygenic model: When are gifted children held back by poor environments?
AB  - From the genetic side, giftedness in cognitive development is the result of
      contribution of many common genetic variants of small effect size, so called
      polygenicity (Spain et al., 2016). From the environmental side, educationalists
      have argued for the importance of the environment for sustaining early potential
      in children, showing that bright poor children are held back in their subsequent
      development (Feinstein, 2003a). Such correlational data need to be complemented
      by mechanistic models showing how gifted development results from the respective
      genetic and environmental influences. A neurocomputational model of cognitive
      development is presented, using artificial neural networks to simulate the
      development of a population of children. Variability was produced by many small
      differences in neurocomputational parameters each influenced by multiple
      artificial genes, instantiating a polygenic model, and by variations in the level
      of stimulation from the environment. The simulations captured several key
      empirical phenomena, including the non-linearity of developmental trajectories,
      asymmetries in the characteristics of the upper and lower tails of the population
      distribution, and the potential of poor environments to hold back bright
      children. At a computational level, 'gifted' networks tended to have higher
      capacity, higher plasticity, less noisy neural processing, a lower impact of
      regressive events, and a richer environment. However, individual instances
      presented heterogeneous contributions of these neurocomputational factors,
      suggesting giftedness has diverse causes.

PMID- 30100646
TI  - Reaction times match IQ for major causes of mortality: Evidence from a population
      based prospective cohort study.
AB  - Introduction: The association of premorbid cognitive ability with all-cause
      mortality is now well established. However, since all-cause mortality is
      relatively uninformative about aetiology, evidence has been sought, and is
      beginning to accumulate, for associations with specific causes of mortality.
      Likewise, the underlying causal pathways may be illuminated by considering
      associations with different measures of cognitive ability. For example, critics
      of IQ type measures point to possible cultural or social biases and there is,
      consequently, a need for more culturally neutral measures such as reaction times.
      We examine the associations of cognitive ability with major causes of mortality,
      including: cardiovascular disease, cancer and respiratory disease and compare the
      results for a standard IQ test, the Alice Heim 4 (AH4), with those for simple and
      four-choice reaction times. Methods: Data were derived from the oldest cohort of
      the West of Scotland Twenty-07 Study. Participants were randomly sampled from the
      Central Clydeside Conurbation, a mainly urban area centred on Glasgow city. At
      baseline, aged 56, they were interviewed in their homes by trained interviewers;
      the AH4 was administered and reaction times measured using a portable electronic
      device. Vital status was ascertained via linkage to the NHS central register. Cox
      regression was used in SAS 9.4 for the main analyses. Adjustments were made for
      sex, smoking status and social class. Results: Full data on AH4, RT and
      covariates were available for 1350 out of 1551. During 29 years of follow-up,
      there were 833 deaths: 279 cardiovascular disease (CVD) (168 CHD; 68 stroke); 291
      cancer; 97 respiratory disease; 42 digestive disease; and 39 dementia. The 85
      remaining deaths were a heterogeneous mixture with no cause accounting for more
      than 14.AH4 scores were associated with most major causes. Digestive disease and
      dementia had similar effect sizes but were not significant. Within cardiovascular
      disease, there was an association with coronary heart disease but not stroke. The
      association with cancer was primarily due to those cancers related to smoking.RT
      measures were mostly associated with the same causes of death. Where significant,
      effects were in the same directions and of similar magnitude. That is, lower AH4
      scores, longer reaction times, and more variable reaction times were all
      associated with increased mortality risk from the major causes of death. A
      summary measure of RT outperformed the AH4 for most causes. Conclusion: The
      association between intelligence with mortality from the major causes is also
      seen with reaction times. That effect sizes are of similar magnitude is
      suggestive of a common cause. It also implies that the association of cognitive
      ability with mortality is unlikely to be due to any social, cultural or
      educational biases that are sometimes ascribed to intelligence measures.

PMID- 30100648
TI  - Promoting Similarity of Sparsity Structures in Integrative Analysis with
      Penalization.
AB  - For data with high-dimensional covariates but small sample sizes, the analysis of
      single datasets often generates unsatisfactory results. The integrative analysis
      of multiple independent datasets provides an effective way of pooling information
      and outperforms single-dataset and several alternative multi-datasets methods.
      Under many scenarios, multiple datasets are expected to share common important
      covariates, that is, the corresponding models have similarity in their sparsity
      structures. However, the existing methods do not have a mechanism to promote the
      similarity in sparsity structures in integrative analysis. In this study, we
      consider penalized variable selection and estimation in integrative analysis. We
      develop an L0-penalty based method, which explicitly promotes the similarity in
      sparsity structures. Computationally it is realized using a coordinate descent
      algorithm. Theoretically it has the selection and estimation consistency
      properties. Under a wide spectrum of simulation scenarios, it has identification
      and estimation performance comparable to or better than the alternatives. In the
      analysis of three lung cancer datasets with gene expression measurements, it
      identifies genes with sound biological implications and satisfactory prediction
      performance.

PMID- 30100650
TI  - Preparation of uranium(III) in a molten chloride salt: a redox mechanistic study.
AB  - The most advanced methodology for the pyroprocessing of spent nuclear fuel is the
      electrorefining of uranium metal in LiCl-KCl eutectic, in which uranium is
      solubilized as U(III). The production of U(III) in LiCl-KCl eutectic by the
      chlorination of uranium metal using BiCl3 has been performed for research
      purposes. In this work, this reaction was studied in-situ by visual observation,
      electronic absorption spectroscopy and electrochemistry at 450  degrees C. The
      most likely mechanism has been determined to involve the initial direct oxidation
      of uranium metal by Bi(III) to U(IV). The dissolved U(IV) then reacts with
      unreacted uranium metal to form U(III).

PMID- 30100651
TI  - Radiosynthesis and reactivity of N-[11C]methyl carbamoylimidazole.
AB  - N-Methyl carbamoylimidazole is a safe and practical alternative to methyl
      isocyanate for carbamoylation reactions. We have developed a new chemical route
      for its synthesis from methyl iodide and applied this to the synthesis of N
      [11C]methyl carbamoylimidazole as a new [11C]synthon to radiolabel biomolecules
      for PET imaging research. N-[11C]methyl carbamoylimidazole was prepared from
      [11C]methyl iodide in 70-74% radiochemical yield (decay corrected) and can be
      used in situ for further reaction without purification. The reactivity of N
      [11C]methyl carbamoylimidazole was demonstrated in a series of
      [11C]carbamoylation reactions.

PMID- 30100649
TI  - The chemo- enzymatic synthesis of labeled l-amino acids and some of their
      derivatives.
AB  - This review compiles the combined chemical and enzymatic synthesis of aromatic l
      amino acids (l-phenylalanine, l-tyrosine, l-DOPA, l-tryptophan, and their
      derivatives and precursors) specifically labeled with carbon and hydrogen
      isotopes, which were elaborated in our research group by the past 20 years. These
      compounds could be then employed to characterize the mechanisms of enzymatic
      reactions via kinetic and solvent isotope effects methods.

PMID- 30100652
TI  - Intellectual property rights and Indian pharmaceutical industry: Present
      scenario.

PMID- 30100653
TI  - Metabolic syndrome-associated cognitive decline in mice: Role of minocycline.
AB  - OBJECTIVE: The objective of the study was to characterize the mechanism
      associated with metabolic syndrome (MetS)-associated cognitive decline and
      determine the effect of minocycline on the above condition in mice. MATERIALS AND
      METHODS: We developed a HFHC diet-induced MetS model in mice. Diagnostic
      characteristics of MetS including waist circumference, lipid levels, blood
      pressure, and fasting blood glucose were measured in these Swiss albino mice.
      Cognitive parameters were measured using passive avoidance and elevated plus maze
      test. Hippocampal acetylcholine esterase (AchE), reduced glutathione (GSH), and
      cytokine levels were measured and histopathological evaluation conducted. The
      MetS animals were administered minocycline (50 mg/kg; 10 days) and the above
      parameters were measured. RESULTS: We successfully induced MetS using HFHC diet
      in mice. Animals showed significantly higher fasting blood glucose levels (P <
      0.001), systolic blood pressure (P < 0.01), waist circumference (P < 0.001), low
      density lipoprotein (P < 0.001), and triglyceride (P < 0.01) and reduced high
      density lipoprotein levels (P < 0.05) compared to control animals. Both
      scopolamine and MetS significantly lowered (P < 0.01) step-down latency and
      increased transfer latency (P < 0.001). MetS animals showed significantly higher
      AchE (P < 0.001) and tumor necrosis factor-alpha (P < 0.001) and Interleukin-1
      beta (P < 0.01) and lower GSH (P < 0.001) levels and reduced both CA1 (P < 0.001)
      and CA3 (P < 0.01) neuronal density compared to controls. Minocycline treatment
      partially reversed the above neurobehavioral and biochemical changes and improved
      hippocampal neuronal density in MetS animals. CONCLUSION: MetS led to hippocampal
      oxidative stress and neuroinflammatory changes with a corresponding loss of
      hippocampal neuronal density and cognitive decline. Anti-inflammatory and
      antioxidant property of minocycline may be responsible for its neuroprotective
      actions in these animals.

PMID- 30100654
TI  - Incidence of multidrug resistance and extended-spectrum beta-lactamase expression
      in community-acquired urinary tract infection among different age groups of
      patients.
AB  - OBJECTIVES: Urinary tract infection (UTI) is a frequent disorder and depends on
      age and gender. Ineffective empiric treatment of UTI is common when associated
      with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and
      Klebsiella pneumoniae. The aim of the study was to investigate the prevalence of
      Gram-negative uropathogens of E. coli and K. pneumoniae in different age groups
      along with the identification of ESBL-producing uropathogens and antimicrobial
      susceptibility profiles. MATERIALS AND METHODS: A total of 247 uropathogens of E.
      coli and K. pneumoniae were collected over a period of 1 year (January-December
      2015) from various diagnostic centers of Karachi city (Pakistan). Antimicrobial
      susceptibility analysis was performed by disc diffusion method, and
      identification of ESBL was performed by double disc synergy test. Categorical
      data of ESBL and non-ESBL uropathogens were analyzed by Pearson's Chi-square
      test. RESULTS: The study of 247 patients with community-acquired UTI comprised
      72% females and 28% males, illustrating an increased prevalence of UTIs among
      females. It was also revealed that 90% belonged to the age group of 16-30 years
      whereas 78% related to the age group of 46-60 years. ESBL was found positive in
      33.5% (63/188) of E. coli and 15.25% (9/59) in K. pneumonia, with a significant
      association i.e., (p =0.007). Amikacin, fosfomycin, imipenem, and
      tazobactam/piperacillin were found to be the effective treatment options. A
      significant association was found between ESBL-producing uropathogens against
      ciprofloxacin, enoxacin, and amoxicillin/clavulanic acid resistance (P < 0.05).
      CONCLUSIONS: It was concluded that for effective treatment of UTIs, appropriate
      screening of ESBL and culture sensitivity must be employed instead of empiric
      treatment.

PMID- 30100655
TI  - Pharmacokinetics and bioavailability of chromium malate and its influence on
      trace metals absorption after oral or intravenous administration.
AB  - OBJECTIVES: In our preliminary study, chromium malate could decrease the blood
      glucose level in mice with diabetes and exhibits good benefits in treating
      glycometabolism and adipose metabolization obstacle in rats with type 2 diabetes.
      This study was aimed at assessing the pharmacokinetics and bioavailability of
      chromium malate and influence on trace metals absorption in rats. METHODS: BAPP
      2.3 pharmacokinetic calculating program (China Pharmaceutical University Medicine
      Center) was used to calculate the pharmacokinetic parameters. Models of type 2
      diabetic mellitus rats were applied to analyzed Ca, Mg, Fe, Cu, and Zn contents.
      RESULTS: The results showed that mean retention time (MRT) in chromium malate
      group was significantly prolonged and the area under the curve (AUC) and relative
      bioavailability of chromium malate (male) group were significant increase
      compared to chromium picolinate group. The serum Ca, Mg, Fe, Cu, and Zn contents
      in chromium malate (at doses of 15 and 20 MUg Cr/kg bw) groups were significantly
      increased compared to control group, chromium trichloride group, and chromium
      picolinate group in type 2 diabetes mellitus rats. CONCLUSIONS: Those results
      indicated that chromium malate can significantly prolong MRT and increase AUC
      (male). Moreover, chromium malate is more effective at treating increased serum
      Ca, Mg, Fe, Cu, and Zn contents compared to chromium trichloride and chromium
      picolinate.

PMID- 30100656
TI  - Potentiation of pentylenetetrazole-induced neuronal damage by dimethyl sulfoxide
      in chemical kindling model in rats.
AB  - OBJECTIVES: Dimethyl sulfoxide (DMSO) is commonly used as a vehicle for many
      hydrophobic drugs. This study aimed at evaluating the effect of low dose of DMSO
      (0.1%) on Pentylenetetrazole(PTZ) induced neuronal damage in rats. MATERIALS AND
      METHODS: Young male Wistar rats (n = 32) were divided into four groups as
      follows: saline control group, DMSO control group, PTZ group (35 mg/kg), and
      combination group (DMSO + PTZ). Animals were observed for seizure score, latency
      to develop kindling, percentage of animals kindled, and histopathological score
      of hippocampus. RESULTS: There was a significant increase in the seizure scores
      and histopathological scores in the combination group as compared to PTZ-treated
      group. The latency to develop kindling was, however, decreased in the combination
      group (4th week) as compared to PTZ (6th week) group. CONCLUSIONS: The present
      study has concluded that 0.1% DMSO in PTZ-induced rat model of epileptogenesis
      needs further optimization and should be used cautiously.

PMID- 30100657
TI  - Clozapine-induced bicytopenia: An unusual side effect.
AB  - Agranulocytosis is a rare documented side effect of clozapine which can be
      associated with grave consequences. When it is associated with other blood
      dyscrasia, prognosis worsens further. In literature, there are very few cases of
      pancytopenia and bicytopenia caused by clozapine. We present a case of
      bicytopenia (reduced white and red blood cells' counts) caused by clozapine
      within a month of therapy and complicated by a Klebsiella pneumoniae infection.
      Patient improved in 3 weeks after stopping clozapine along with medical
      management in the Intensive Care Unit. Such side effects, though rare, can be
      life threatening and warrants intermittent complete blood monitoring besides
      regular assessment of granulocytes and neutrophils when any patient is prescribed
      clozapine.

PMID- 30100658
TI  - Is inhaled glucocorticoids the only culprit in angina bullosa hemorrhagica?
AB  - Angina bullosa hemorrhagica (ABH) is an infrequent dermatosis characterized by
      acute onset of hemorrhagic bulla in the oral cavity. Clinical presentation of ABH
      may be quite worrisome, and clinicians often feel skeptical regarding their
      clinical diagnosis and lack confidence in managing this distinct entity. Indeed,
      ABH is a completely benign and self-limited disorder. The exact etiopathogenesis
      of ABH is still unknown. There have been reports in the literature addressing a
      central role for mechanical instability of the epithelial-connective tissue
      connection in the pathogenesis of ABH. Moreover, it has been claimed that long
      term usage of inhaled glucocorticoids (GCs) is involved in the development of
      ABH, since most of the reported cases are asthmatic patients, who were treated
      with inhaled GCs, and GCs are well known for their degradative activities on
      collagen formation. Here, we describe a case with ABH, who had a drug history of
      inhaled GCs and nonsteroidal anti-inflammatory drugs (NSAIDs). We assume that our
      case not only supports the association of inhaled GCs with ABH but also suggests
      a possible role for NSAIDs in the pathogenesis of ABH.

PMID- 30100660
TI  - Clinical trials waiver in India-some considerations.

PMID- 30100659
TI  - Well-tolerated oral cyclosporine in a case of hypersensitivity to parenteral
      cyclosporine in postallogeneic bone marrow transplantation.
AB  - Cyclosporine is one of the main drugs used for the prophylaxis of graft versus
      host disease in bone marrow transplanted patients. Hypersensitivity reaction to
      intravenous cyclosporine is rare and might be due to its vehicle polyoxyethylated
      castor oil, Cremophor EL. The exact mechanism is unknown, but IgE and IgG
      antibodies, complement, and histamine release have been considered to play a role
      in the development of this reaction. Here, we describe a case of anaphylaxis to
      intravenous cyclosporine, which was developed in a 19-year-old Iranian female
      with acute myeloid leukemia who underwent allogeneic bone marrow transplantation
      from her sister. The corn oil-based soft gelatin capsule (Sandimmune(r)) was
      substituted with no reaction. Our observation along with the previous reports
      confirms the role of Cremophor EL in hypersensitivity reaction to cyclosporine,
      according to which, modifying the formulation of the intravenous (IV) form could
      be the solution for this problem.

PMID- 30100661
TI  - The Social Structure of Mortgage Discrimination.
AB  - In the decade leading up to the U.S. housing crisis, black and Latino borrowers
      disproportionately received high-cost, high-risk mortgages-a lending disparity
      well documented by prior quantitative studies. We analyze qualitative data from
      actors in the lending industry to identify the social structure though which this
      mortgage discrimination took place. Our data consist of 220 depositions,
      declarations, and related exhibits submitted by borrowers, loan originators,
      investment banks, and others in fair lending cases. Our analyses reveal specific
      mechanisms through which loan originators identified and gained the trust of
      black and Latino borrowers in order to place them into higher-cost, higher-risk
      loans than similarly situated white borrowers. Loan originators sought out lists
      of individuals already borrowing money to buy consumer goods in predominantly
      black and Latino neighborhoods to find potential borrowers, and exploited
      intermediaries within local social networks, such as community or religious
      leaders, to gain those borrowers' trust.

PMID- 30100662
TI  - Power, Ethics and Obligation.

PMID- 30100663
TI  - Estimation and testing in targeted goup sequential covariate-adjusted randomized
      clinical trials.
AB  - This article is devoted to the construction and asymptotic study of adaptive
      group sequential covariate-adjusted randomized clinical trials analyzed through
      the prism of the semipara-metric methodology of targeted maximum likelihood
      estimation (TMLE). We show how to build, as the data accrue group-sequentially, a
      sampling design which targets a user-supplied optimal design. We also show how to
      carry out a sound TMLE statistical inference based on such an adaptive sampling
      scheme (therefore extending some results known in the i.i.d setting only so far),
      and how group-sequential testing applies on top of it. The procedure is robust
      (i.e., consistent even if the working model is misspecified). A simulation study
      confirms the theoretical results, and validates the conjecture that the procedure
      may also be efficient.

PMID- 30100664
TI  - Natural Disasters, Social Protection, and Risk Perceptions.
AB  - Natural disasters give rise to loss and damage and may affect subjective
      expectations about the prevalence and severity of future disasters. These
      expectations might then in turn shape individuals' investment behaviors,
      potentially affecting their incomes in subsequent years. As part of an emerging
      literature on endogenous preferences, economists have begun studying the
      consequences that exposure to natural disasters have on risk attitudes,
      perceptions, and behavior. We add to this field by studying the impact of being
      struck by the December 2012 Cyclone Evan on Fijian households' risk attitudes and
      subjective expectations about the likelihood and severity of natural disasters
      over the next 20 years. The randomness of the cyclone's path allows us to
      estimate the causal effects of exposure on both risk attitudes and risk
      perceptions. Our results show that being struck by an extreme event substantially
      changes individuals' risk perceptions as well as their beliefs about the
      frequency and magnitude of future shocks. However, we find sharply distinct
      results for the two ethnicities in our sample, indigenous Fijians and Indo
      Fijians; the impact of the natural disaster aligns with previous results in the
      literature on risk attitudes and risk perceptions for Indo-Fijians, whereas they
      have little to no impact on those same measures for indigenous Fijians. To
      provide welfare implications for our results, we compare households' risk
      perceptions to climate and hydrological models of future disaster risk, and find
      that both ethnic groups over-infer the risk of future disasters relative to the
      model predictions. If such distorted beliefs encourage over-investment in
      preventative measures at the cost of other productive investments, these biases
      could have negative welfare impacts. Understanding belief biases and how they
      vary across social contexts may thus help decision makers design policy
      instruments to reduce such inefficiencies, particularly in the face of climate
      change.

PMID- 30100666
TI  - Circular data in biology: advice for effectively implementing statistical
      procedures.
AB  - Circular data are common in biological studies. The most fundamental question
      that can be asked of a sample of circular data is whether it suggests that the
      underlying population is uniformly distributed around the circle, or whether it
      is concentrated around at least one preferred direction (e.g. a migratory goal or
      activity phase). We compared the statistical power of five commonly used tests
      (the Rayleigh test, the V-test, Watson's test, Kuiper's test and Rao's spacing
      test) across a range of different unimodal scenarios. The V-test showed higher
      power for symmetrical distributions, Rao's spacing performed worst for all
      explored unimodal distributions tested and the remaining three tests showed very
      similar performance. However, the V-test only applies if the hypothesis is
      restricted to one (pre-specified) direction of interest. In all other unimodal
      cases, we recommend using the Rayleigh test. Much less explored is the multimodal
      case with data concentrated around several directions. We performed power
      simulations for a variety of multimodal situations, testing the performance of
      the widely used Rayleigh, Rao's, Watson, and Kuiper's tests as well as the more
      recent Bogdan and Hermans-Rasson tests. Our analyses of alternative statistical
      methods show that the commonly used tests lack statistical power in many of
      multimodal cases. Transformation of the raw data (e.g. doubling the angles) can
      overcome some of the issues, but only in the case of perfect f-fold symmetry.
      However, the Hermans-Rasson method, which is not yet implemented in any software
      package, outcompetes the alternative tests (often by substantial margins) in most
      of the multimodal situations explored. We recommend the wider uptake of the
      powerful but hitherto neglected Hermans-Rasson method. In summary, we provide
      guidance for biologists helping them to make decisions when testing circular data
      for single or multiple departures from uniformity.

PMID- 30100665
TI  - The role of complex cues in social and reproductive plasticity.
AB  - Phenotypic plasticity can be a key determinant of fitness. The degree to which
      the expression of plasticity is adaptive relies upon the accuracy with which
      information about the state of the environment is integrated. This step might be
      particularly beneficial when environments, e.g. the social and sexual context,
      change rapidly. Fluctuating temporal dynamics could increase the difficulty of
      determining the appropriate level of expression of a plastic response. In this
      review, we suggest that new insights into plastic responses to the social and
      sexual environment (social and reproductive plasticity) may be gained by
      examining the role of complex cues (those comprising multiple, distinct sensory
      components). Such cues can enable individuals to more accurately monitor their
      environment in order to respond adaptively to it across the whole life course. We
      briefly review the hypotheses for the evolution of complex cues and then adapt
      these ideas to the context of social and sexual plasticity. We propose that the
      ability to perceive complex cues can facilitate plasticity, increase the
      associated fitness benefits and decrease the risk of costly 'mismatches' between
      phenotype and environment by (i) increasing the robustness of information gained
      from highly variable environments, (ii) fine-tuning responses by using multiple
      strands of information and (iii) reducing time lags in adaptive responses. We
      conclude by outlining areas for future research that will help to determine the
      interplay between complex cues and plasticity.

PMID- 30100668
TI  - [The Use Of Pulmonary Gene Therapy In The Treatment Of Experimental Models Of
      Pneumonia And Septicemia].

PMID- 30100667
TI  - Sex differences in life history, behavior, and physiology along a slow-fast
      continuum: a meta-analysis.
AB  - The pace-of-life syndrome (POLS) hypothesis predicts that behavior and physiology
      covary with life history. Evidence for such covariation is contradictory,
      possibly because systematic sources of variation (e.g. sex) have been neglected.
      Sexes often experience different selection pressures leading to sex-specific
      allocation between reproduction and self-maintenance, facilitating divergence in
      life-history. Sex-specific differences in means and possibly variances may
      therefore play a key role in the POLS framework. We investigate whether sexes
      differ in means and variances along the fast-slow pace-of-life continuum for life
      history and physiological and behavioral traits. In addition, we test whether
      social and environmental characteristics such as breeding strategy, mating
      system, and study environment explain heterogeneity between the sexes. Using meta
      analytic methods, we found that populations with a polygynous mating system or
      for studies conducted on wild populations, males had a faster pace-of-life for
      developmental life-history traits (e.g., growth rate), behavior, and physiology.
      In contrast, adult life-history traits (e.g., lifespan) were shifted towards
      faster pace-of-life in females, deviating from the other trait categories.
      Phenotypic variances were similar between the sexes across trait categories and
      were not affected by mating system or study environment. Breeding strategy did
      not influence sex differences in variances or means. We discuss our results in
      the light of sex-specific selection that might drive sex-specific differences in
      pace-of-life and ultimately POLS.

PMID- 30100669
TI  - Aharonov and Bohm versus Welsh eigenvalues.
AB  - We consider a class of two-dimensional Schrodinger operator with a singular
      interaction of the delta type and a fixed strength beta supported by an infinite
      family of concentric, equidistantly spaced circles, and discuss what happens
      below the essential spectrum when the system is amended by an Aharonov-Bohm flux
      alpha?[0,12] in the center. It is shown that if beta?0 , there is a critical
      value alphacrit?(0,12) such that the discrete spectrum has an accumulation point
      when alpha<alphacrit , while for alpha>=alphacrit the number of eigenvalues is at
      most finite, in particular, the discrete spectrum is empty for any fixed
      alpha?(0,12) and |beta| small enough.

PMID- 30100670
TI  - The Effects of Leadership and Job Autonomy on Vitality: Survey and Experimental
      Evidence.
AB  - Vitality refers to the experience of having energy available to one's self. Vital
      employees are full of positive energy when they work, and feel mentally and
      physically strong. Such employees often show higher job performance and lower
      stress than their less vital colleagues. Despite the importance of vitality, few
      public administration studies have studied vitality. More generally, by focusing
      on vitality, we aim to bring a "positive psychology" perspective into the domain
      of public administration. We analyze whether two important job characteristics
      (leader's task communication and job autonomy) affect vitality. We use a multi
      method design. A large-scale survey (N = 1,502) shows that leader's task
      communication and job autonomy are positively related to vitality. A lab
      experiment (N = 102) replicated these findings, showing cause-and-effect
      relationships. In conclusion, public organizations can potentially increase
      employee vitality (a) by increased task communication from leaders and (b) by
      providing employees with greater job autonomy.

PMID- 30100672
TI  - How To Get Mechanistic Information from Partial Pressure-Dependent Current
      Voltage Measurements of Oxygen Exchange on Mixed Conducting Electrodes.
AB  - The oxygen incorporation and evolution reaction on mixed conducting electrodes of
      solid oxide fuel or electrolysis cells involves gas molecules as well as ionic
      and electronic point defects in the electrode. The defect concentrations depend
      on the gas phase and can be modified by the overpotential. These
      interrelationships make a mechanistic analysis of partial pressure-dependent
      current-voltage experiments challenging. In this contribution it is described how
      to exploit this complex situation to unravel the kinetic roles of surface
      adsorbates and electrode point defects. Essential is a counterbalancing of oxygen
      partial pressure and dc electrode polarization such that the point defect
      concentrations in the electrode remain constant despite varying the oxygen
      partial pressure. It is exemplarily shown for La0.6Sr0.4FeO3-delta (LSF) thin
      film electrodes on yttria-stabilized zirconia how mechanistically relevant
      reaction orders can be obtained from current-voltage curves, measured in a three
      electrode setup. This analysis strongly suggests electron holes as the limiting
      defect species for the oxygen evolution on LSF and reveals the dependence of the
      oxygen incorporation rate on the oxygen vacancy concentration. A virtual
      independence of the reaction rate from the oxygen partial pressure was
      empirically found for moderate oxygen pressures. This effect, however, arises
      from a counterbalancing of defect and adsorbate concentration changes.

PMID- 30100671
TI  - Genomic and Transcriptomic Analysis Identified Gene Clusters and Candidate Genes
      for Oil Content in Peanut (Arachis hypogaea L.).
AB  - Peanut (Arachis hypogaea), a major source of vegetable oil in many Asian
      countries, has become an integral part of human diet globally due to its high
      nutritional properties and option to consume in different forms. In order to meet
      the demand of vegetable oil, many peanut breeding programs of China have
      intensified their efforts in increasing oil content in newly bred varieties for
      reducing the import of edible oils in China. In this context, transcriptome
      sequencing data generated on 49 peanut cultivars were analyzed to identify
      candidate genes and develop molecular markers for seed oil content across
      multiple environments. Transcriptome analysis identified 5458 differentially
      expressed genes (DEGs) including 2243 positive DEGs and 3215 negative DEGs
      involved in oil synthesis process. Genome-wide association study identified 48
      significant insertion/deletion (InDel) markers associated with seed oil content
      across five environments. A comparative genomics and transcriptomics analysis
      detected a total of 147 common gene clusters located in 17 chromosomes.
      Interestingly, an InDel cluster associated with seed oil content on A03
      chromosome was detected in three different environments. Candidate genes
      identified on A03 form a haplotype, in which variable alleles were found to be
      different in oil content in an independent population. This locus is important
      for understanding the genetic control of peanut oil content and may be useful for
      marker-assisted selection in peanut breeding programs.

PMID- 30100673
TI  - Prenatal vitamin D and enamel hypoplasia in human primary maxillary central
      incisors: a pilot study.
AB  - Background: Enamel hypoplasia (EH) increases risk for dental caries and also is
      associated with vitamin D deficiencies. This pilot study evaluates the
      feasibility to determine the association of human maternal circulating vitamin D
      concentrations during pregnancy and EH in infant's teeth that develop in utero.
      Methods: A pilot population of 37 children whose mothers participated in a RCT of
      vitamin D supplementation during pregnancy was evaluated. Major outcome was EH
      and major exposure was maternal monthly serum circulating 25(OH)D concentrations
      during pregnancy. EH was assessed using the Enamel Defect Index and digital
      images made by a ProScope High ResolutionTM handheld digital USB microscope at
      50x magnification. Results: During initial 8 weeks of study, 29/37 children had
      evaluable data with mean age of 3.6 +/- 0.9 years; 48% male; and 45% White, 31%
      Hispanic, and 24% Black. EH was identified in 13 (45%) of the children. Maternal
      mean 25(OH)D concentrations were generally lower for those children with EH.
      Conclusions: Preliminary results suggest follow-up of children of mothers in a
      vitamin D supplementation RCT during pregnancy provides an important approach to
      study the etiology of EH in the primary teeth. Further study is needed to discern
      thresholds and timing of maternal serum 25(OH)D concentrations during pregnancy
      associated with absence of EH in teeth that develop in utero. Potential dental
      public health implications for prevention of early childhood caries via sound
      tooth structure as related to maternal vitamin D sufficiency during pregnancy
      need to be determined.

PMID- 30100674
TI  - Bringing cultured meat to market: Technical, socio-political, and regulatory
      challenges in cellular agriculture.
AB  - Background: Cultured meat forms part of the emerging field of cellular
      agriculture. Still an early stage field it seeks to deliver products
      traditionally made through livestock rearing in novel forms that require no, or
      significantly reduced, animal involvement. Key examples include cultured meat,
      milk, egg white and leather. Here, we focus upon cultured meat and its technical,
      socio-political and regulatory challenges and opportunities. Scope and approach:
      The paper reports the thinking of an interdisciplinary team, all of whom have
      been active in the field for a number of years. It draws heavily upon the
      published literature, as well as our own professional experience. This includes
      ongoing laboratory work to produce cultured meat and over seventy interviews with
      experts in the area conducted in the social science work. Key findings and
      conclusions: Cultured meat is a promising, but early stage, technology with key
      technical challenges including cell source, culture media, mimicking the in-vivo
      myogenesis environment, animal-derived and synthetic materials, and bioprocessing
      for commercial-scale production. Analysis of the social context has too readily
      been reduced to ethics and consumer acceptance, and whilst these are key issues,
      the importance of the political and institutional forms a cultured meat industry
      might take must also be recognised, and how ambiguities shape any emergent
      regulatory system.

PMID- 30100675
TI  - Towards standardization of training and practice of reconstructive microsurgery:
      an evidence-based recommendation for anastomosis thrombosis prophylaxis.
AB  - Background: Despite significant improvements in survival rates, free flap
      failures still occur even in experienced hands and are most commonly due to
      arterial or venous thrombosis. In the absence of an evidence-based guideline on
      the prevention of thrombosis, we reviewed the literature to assess the evidence
      base for commonly used interventions aimed at its prevention. Methods: A
      comprehensive literature search was performed using the following keywords "free
      flap" and microsurgery with "pre-operative screening," "prevention of
      thrombosis," "ketorolac," "heparin," "low molecular weight heparin," "aspirin,"
      "dextran," and "statins." Results: Thirteen clinical studies were included in
      this review. No high-level evidence is available to support any perioperative or
      postoperative interventions aimed at reducing the risk of flap thrombosis.
      Conclusions: Higher level studies are needed to investigate the clinical use of
      antithrombotic medications in microsurgery; however, given the small failure
      rates in modern practice, these will need to be large multicenter trials in order
      to reach sufficient power.Level of Evidence: Level III, risk/prognostic study.

PMID- 30100676
TI  - Is single-stage implant-based breast reconstruction (SSBR) with an acellular
      matrix safe?: StratticeTM or Meso Biomatrix(r) in SSBR.
AB  - Background: Acellular matrices (AM) might enable a direct single-stage breast
      reconstruction procedure resulting in an improved efficacy of the reconstruction
      phase for patients. Safety concerns are an important issue due to a recent study
      which shows that single-stage breast reconstruction with StratticeTM resulted in
      more complications versus a two-stage reconstruction. Therefore, the goal of this
      study is to compare the short- and long-term complications of a single-stage
      breast reconstruction with the use of two types of AM (StratticeTM and Meso
      Biomatrix(r)) versus two-stage breast reconstruction without the use of an AM.
      Methods: Cohort study with single-stage breast reconstruction with StratticeTM (n
      = 28) or Meso BioMatrix(r) (n = 20) or two-stage breast reconstruction without an
      AM (n = 36) at the Maastricht Academic Hospital, the Netherlands. All
      complications, in particular major complications with the need for re-admission
      to the hospital, re-exploration, and implant explantation, were the primary
      outcome measures. A 1-year follow-up was achieved for all patients. Results:
      Baseline characteristics of all 52 patients were similar between groups. There
      was a significantly higher complication rate in the single-stage AM groups with
      loss of the implant in 40.0% of the breasts from the Meso BioMatrix(r) group and
      in 10.7% of the StratticeTM group compared to no implant loss in the control
      group. Conclusions: This cohort study clearly suggests that the use of a single
      stage breast reconstruction is not safe with the use of these AMs. Well-designed
      prospective studies that guarantee the safety of those matrices should be
      published before these AMs are used in implant-based surgery.Level of Evidence:
      Level III, risk / prognostic study.

PMID- 30100678
TI  - Managing complex trauma injuries in the elderly: a case report of a free flap and
      circular frame in a 95-year old patient with an open IIIB tibial fracture.
AB  - : In an ageing population, increasing numbers of patients over the age of 70 are
      sustaining severe trauma. These patients require careful multidisciplinary team
      (MDT) management with careful consideration of existing co-morbidities, as such
      their treatment should be individually tailored. We present the case of a patient
      believed to be the oldest documented patient treated in a trauma setting with
      free flap and circular frame fixation to an open tibial fracture. A 95-year-old
      male presented to the Level 1 Major Trauma Centre (MTC) with multiple injuries
      after a pedestrian vs car incident. His injury severity score (ISS) was 22. For
      treatment of his open tibial fracture, he required soft tissue coverage with a
      free anterolateral thigh (ALT) flap, and circular frame application. Microsurgery
      was performed after consultation with the MDT and was uneventful. The circular
      frame was removed after 10 months and the patient went on to regain pre-injury
      mobility. Use of free tissue transfer in elderly patients is well documented in
      the elective setting, but less so in trauma. This case demonstrates that careful
      patient selection, attention to detail and MDT working can result in an excellent
      outcome for the patient. The challenges faced in treating this patient will be
      described in detail. LEVEL OF EVIDENCE: Level V, therapeutic study.

PMID- 30100677
TI  - An enhanced fresh cadaveric model for reconstructive microsurgery training.
AB  - Background: Performing microsurgery requires a breadth and depth of experience
      that has arguably been reduced as result of diminishing operating exposure. Fresh
      frozen cadavers provide similar tissue handling to real-time operating; however,
      the bloodless condition restricts the realism of the simulation. We describe a
      model to enhance flap surgery simulation, in conjunction with qualitative
      assessment. Methods: The fresh frozen cadaveric limbs used in this study were
      acquired by the University. A perfused fresh cadaveric model was created using a
      gelatin and dye mixture in a specific injection protocol in order to increase the
      visibility and realism of perforating vessels, as well as major vessels. A
      questionnaire was distributed amongst 50 trainees in order to assess benefit of
      the model. Specifically, confidence, operative skills, and transferable
      procedural-based learning were assessed. Results: Training with this cadaveric
      model resulted in a statistically significant improvement in self-reported
      confidence (p < 0.005) and prepared trainees for unsupervised bench work (p <
      0.005). Respondents felt that the injected model allowed easier identification of
      vessels and ultimately increased the similarity to real-time operating. Our
      analysis showed it cost L10.78 and took 30 min. Conclusions: Perfusion of
      cadaveric limbs is both cost- and time-effective, with significant improvement in
      training potential. The model is easily reproducible and could be a valuable
      resource in surgical training for several disciplines.Level of Evidence: Not
      ratable.

PMID- 30100679
TI  - Impacts of gold nanoparticles on MHD mixed convection Poiseuille flow of
      nanofluid passing through a porous medium in the presence of thermal radiation,
      thermal diffusion and chemical reaction.
AB  - Impacts of gold nanoparticles on MHD Poiseuille flow of nanofluid in a porous
      medium are studied. Mixed convection is induced due to external pressure gradient
      and buoyancy force. Additional effects of thermal radiation, chemical reaction
      and thermal diffusion are also considered. Gold nanoparticles of cylindrical
      shape are considered in kerosene oil taken as conventional base fluid. However,
      for comparison, four other types of nanoparticles (silver, copper, alumina and
      magnetite) are also considered. The problem is modeled in terms of partial
      differential equations with suitable boundary conditions and then computed by
      perturbation technique. Exact expressions for velocity and temperature are
      obtained. Graphical results are mapped in order to tackle the physics of the
      embedded parameters. This study mainly focuses on gold nanoparticles; however,
      for the sake of comparison, four other types of nanoparticles namely silver,
      copper, alumina and magnetite are analyzed for the heat transfer rate. The
      obtained results show that metals have higher rate of heat transfer than metal
      oxides. Gold nanoparticles have the highest rate of heat transfer followed by
      alumina and magnetite. Porosity and magnetic field have opposite effects on
      velocity.

PMID- 30100680
TI  - Uncommon cause of complicated myocardial infarction with normal coronary arteries
      in a Saudi patient.
AB  - A case of a young Saudi patient with a previous diagnosis of bronchial asthma,
      nasal polyps, and chronic smoker, presented with atypical chest pain, elevated
      serum troponin and borderline ischemic electrocardiogram (ECG) changes, with no
      significant regional wall motion abnormalities at bedside echocardiography is
      reported. The patient was admitted to the coronary care unit for continuous
      monitoring as possible acute coronary syndrome, non-ST elevation myocardial
      infarction (STEMI). One hour after admission, the patient had ventricular
      fibrillation (VF) cardiac arrest that required three DC shocks and amiodarone
      bolus before returning of spontaneous circulation, which followed the fourth
      shock. The resuscitation took 15 minutes of cardiopulmonary resuscitation (CPR).
      An immediate 12-leads ECG showed significant ST elevation in precordial leads
      that mandate an urgent coronary angiogram that revealed patent coronary arteries,
      therefore spasm of normal coronary arteries was postulated as the operative
      factor. The cardiac magnetic resonance image (MRI) showed a picture of transmural
      anterior myocardial infarction, which correlates with the follow up
      echocardiogram reporting hypokinetic anterior wall. A complete history was taken
      and no use of illicit drugs or alcohol was found. The unusual presentation in
      such a patient with evidence of extensive anterior STEMI and normal coronary
      arteries raise the thought of considering uncommon causes. In view of previous
      medical history and laboratory evidence of eosinophilia, Kounis syndrome was
      considered dominant in the differential diagnosis.

PMID- 30100681
TI  - Significant left ventricular outflow tract obstruction secondary to systolic
      anterior motion in a patient without hypertrophic cardiomyopathy: An
      echocardiographic study.
AB  - Dynamic left ventricular outflow tract obstruction (LVOTO) can be hemodynamically
      significant and can adversely affect the heart and quality of life. It is caused
      by systolic anterior motion (SAM) of the anterior mitral valve into the LVOT. The
      mechanism underlying SAM has been an area of special interest. However, SAM
      occurrence in the absence of septal hypertrophy is exceedingly uncommon. Here we
      present a case of a young male patient who sought medical care with a complaint
      of exertional dyspnea, New York Heart Association functional Class 2-3, and was
      found to have SAM and severe LVOTO at rest without hypertrophic cardiomyopathy.
      Continuous wave Doppler signal showed a peak velocity of 4.96 m/s along the LVOT,
      with a pressure gradient at rest of 98.44 mmHg, calculated using the modified
      Bernoulli equation. The patient is not known to have any medical conditions, nor
      had a family history of cardiac condition or sudden death. Trans-thoracic
      echocardiography showed concentric remodeling of the LV without hypertrophy.
      Trans-esophageal echocardiography was performed for further assessment of the
      anatomy. The anterior mitral leaflet (AML) and posterior mitral leaflet (PML)
      lengths were 3.7 cm and 1.3 cm, respectively (normal AML < 3 cm; normal PML < 1.5
      cm). In our patient, the LVOTO is significant enough to result in a decreased
      cardiac output, which explains the symptoms experienced, due to which he
      developed concentric remodeling. The only finding in this patient explaining SAM
      is an elongated AML.

PMID- 30100682
TI  - Prospects for Millimeter-Wave Compliance Measurement Technologies.

PMID- 30100683
TI  - Ambulatory Pump Safety: Managing Home Infusion Patients Admitted to The Emergency
      Department and Hospital.
AB  - Managing home infusion patients in the hospital and emergency department.

PMID- 30100685
TI  - Drug and Device News.
AB  - Approvals, new indications, regulatory activities, and more.

PMID- 30100684
TI  - FDA Guidance on 503B Provides Leeway: Outsourcing Facilities Can Be Co-Located
      With 503A Pharmacies.
AB  - FDA guidance on outsourcing facilities and 503A pharmacies.

PMID- 30100686
TI  - Pharmaceutical Approval Update.
AB  - Lofexidine hydrocholoride (Lucemyra) for opioid withdrawal; erenumab-aooe
      (Aimovig) for migraine; and sodium zirconium cyclosilicate (Lokelma) for
      hyperkalemia.

PMID- 30100688
TI  - Clarification of Drug Allergy Information Using a Standardized Drug Allergy
      Questionnaire and Interview.
AB  - Background: Vague, incomplete, or inaccurate drug-allergy histories can be
      detrimental to patient safety and affect patient care. There is an increased
      chance of medication errors if details of a drug allergy are not documented.
      Incomplete or inaccurate allergy histories may also result in increased time
      spent by health care providers to clarify an order in question. Published
      literature from the early 1990s showed that a patient interview can facilitate
      collection of more complete allergy information and could lead to the removal of
      a documented drug allergy in approximately one-third of patients. Purpose: This
      quality-improvement project was conducted to improve the process of collecting
      drug-allergy information at our institution. Description: The primary objective
      of this project was to determine the number of patients with a clinically
      relevant change in allergy history after a standardized drug-allergy
      questionnaire and interview compared with documentation prior to the interview.
      This was a descriptive, prospective quality improvement project of a standardized
      drug-allergy questionnaire and interview. Patients were asked about the history
      of their allergic reaction, including the drug, route, nature of reaction,
      treatment of reaction, and time since reaction. Results: A total of 301 patient
      allergy profiles were reviewed. After screening, 202 patients were included and
      interviewed, for a total of 509 drug allergies. One hundred twenty-three patients
      (61%) had a need for a clinically relevant change in allergy history after an
      interview. A total of 228 changes were made to patient allergy profiles. Adding
      the allergy reaction accounted for 131 of the changes. Also, there were 185
      allergies documented prior to the interview that were categorized as
      unclear/vague, which was significantly reduced to 112 after the interview (P <
      0.0001). Conclusion: More complete drug-allergy information was obtained after
      executing a standardized drug-allergy questionnaire and interview.

PMID- 30100687
TI  - Real-World Evidence: Promise and Peril For Medical Product Evaluation.
AB  - Randomized controlled trials have long been the gold standard for evidence in
      medical product evaluation, but there is growing support for the use of real
      world evidence (RWE). The authors review the benefits and limitations of RWE and
      discuss the implications for P&T committees.

PMID- 30100689
TI  - Variation in Generic Drug Manufacturers' Product Characteristics.
AB  - Objectives: Studies suggest appearance may be an important factor in medication
      nonadherence. This study was undertaken to characterize the range of appearances
      and costs of 16 oral solid generic medications in four major chronic
      diseases/conditions. Methods: We identified frequently prescribed medications in
      four therapeutic classes-antidiabetics, 3-hydroxy-3-methylglutaryl-coenzyme A
      reductase inhibitors (statins), beta blockers, and heart failure drugs-and
      verified that each had at least three generic manufacturer sources in 2016. The
      color, shape, scoring, and size for each formulation were compared. Prices were
      determined based on manufacturers' self-reported wholesale acquisition costs
      effective December 31, 2016. Results: We identified 40 unique manufacturers for
      the antidiabetics, 35 for the statins, 38 for the beta blockers, and 71 for the
      heart failure agents. For all 16 drugs across all four disease states, there was
      an average of three colors, two shapes, 11 manufacturers, and four appearances
      when color and shape together are considered. The cost variance per drug ranged
      from 2% to more than 62,253%. Conclusion: Substantial appearance variation among
      generically equivalent products raises the strong possibility that patients may
      experience product switches that could increase the likelihood of nonadherence.
      Our data support the need to further study drug appearance changes and
      interventions as a potential factor affecting chronic disease adherence outcomes.

PMID- 30100690
TI  - Old and New Drug Classes Expanding To Include Glaucoma Treatments.
AB  - Poor patient adherence is fueling keen interest in the development of drugs for
      glaucoma management. Several long-acting formulations of existing medications are
      in the early stages of development, as are new therapeutic classes such as
      guanylate cyclase activators.

PMID- 30100691
TI  - American Society of Clinical Oncology.
AB  - We review key findings in the areas of prostate cancer, non-small-cell lung
      cancer, breast cancer, esophageal cancer, pancreatic cancer, leukemias,
      metastatic colon cancer, and one session on molecular profiling guidance of
      therapy.

PMID- 30100692
TI  - Research Briefs.

PMID- 30100693
TI  - Synthesis and biological investigations of 3beta-aminotropane arylamide
      derivatives with atypical antipsychotic profile.
AB  - This work is a continuation of our previous research, concentrating this time on
      lead structure modification to increase the 5-HT1A receptor affinity and water
      solubility of designed compounds. Therefore, the compounds synthesised within the
      present project included structural analogues of 3beta-acylamine derivatives of
      tropane with the introduction of a methyl substituent in the benzyl ring and a 2
      quinoline, 3-quinoline, or 6-quinoline moiety. A series of novel 3beta
      aminotropane derivatives was evaluated for their affinity for 5-HT1A, 5-HT2A, and
      D2 receptors, which allowed for the identification of compounds 12e, 12i, and 19a
      as ligands with highest affinity for the tested receptors; they were then
      subjected to further evaluation in preliminary in vivo studies. Selected
      compounds 12i and 19a displayed antipsychotic properties in the d-amphetamine
      induced and MK-801-induced hyperlocomotor activity test in mice. Moreover,
      compound 19a showed significant antidepressant-like activity in the forced swim
      test in mice.

PMID- 30100694
TI  - Assessing Autism Spectrum Disorder in People with Sensory Impairments Combined
      with Intellectual Disabilities.
AB  - People with sensory impairments combined with intellectual disabilities show
      behaviours that are similar to Autism Spectrum Disorder (ASD). The instrument
      Observation of Autism in people with Sensory and Intellectual Disabilities
      (OASID) was developed to diagnose ASD in this target group. The current study
      focuses on the psychometric properties of OASID. Sixty individuals with
      intellectual disabilities in combination with visual impairments and/or
      deafblindness participated in this study. The OASID assessment was administered
      and rated by three independent observers. By means of expert consensus cut-off
      scores for OASID were created. To determine the concurrent validity OASID was
      compared with the Pervasive Developmental Disorder for People with Mental
      Retardation (PDD-MRS) and the Childhood Autism Rating Scale second edition (CARS
      2). The intra-rater reliability, the inter-rater reliability, internal
      consistency and concurrent validity of OASID were good to excellent. Cut-off
      scores were established based on criteria from the DSM-5. OASID was able to
      differentiate between four severity levels of ASD.

PMID- 30100696
TI  - The Adolescent HIV Communication Belief Scale: Preliminary Reliability and
      Validity.
AB  - Globally, there are nearly 2 million HIV positive children, many of whom are
      adolescents. The majority have perinatally acquired HIV. A key challenge for this
      population is communicating about HIV to meet emotional and practical needs.
      Despite evidence of its benefits, HIV communication in adolescents with HIV is
      rare. To enhance HIV communication, individuals' beliefs may need to be taken
      into account. There is no measure of beliefs about HIV communication for
      adolescents living with HIV. A seven-item measure of HIV communication beliefs
      was developed and administered to 66 adolescents with HIV in the UK (39 female;
      aged 12-16 years). Data were explored using principal component analysis.
      Preliminary criterion-related validity was assessed by examining relationships
      between the measure and communication occurrence, frequency and intention.
      Preliminary construct validity was assessed by examining relationships between
      the measure and HIV stigma, HIV disclosure cognition and affect, quality of life
      and self-perception. Two factors were revealed: communication self-efficacy and
      normative beliefs; and communication attitudes. The full scale and its subscales
      were internally consistent. The total score showed statistically significant
      positive relationships with HIV communication intention, HIV disclosure
      cognitions and affect, and HIV stigma but not with other variables. Preliminary
      evidence of the measure's good psychometric properties suggests it may be helpful
      in outlining relationships between HIV communication beliefs and other
      constructs. It may also be useful in testing interventions that aim to enhance
      HIV communication in this population. Further work needs to be done to establish
      the scale's psychometric properties.

PMID- 30100695
TI  - Relationship of Mindfulness to Distress and Cortisol Response in Adolescent Girls
      At-Risk for Type 2 Diabetes.
AB  - Altered stress response theoretically contributes to the etiology of
      cardiometabolic disease. Mindfulness may be a protective buffer against the
      effects of stress on health outcomes by altering how individuals evaluate and
      respond to stress. We engaged adolescent girls at risk for developing Type 2
      diabetes in a cold-pressor test in order to determine the relationship of
      dispositional mindfulness to cortisol response and subjective stress, including
      perceived pain and unpleasantness during the stressor, and negative affect
      following the stressor. We also evaluated mindfulness as a moderator of
      psychological distress (depressive/anxiety symptoms) and stress response.
      Participants were 119 girls age 12-17 years with overweight/obesity, family
      history of diabetes, and mild-to-moderate depressive symptoms. Greater
      mindfulness was associated with less perceived pain and negative affect, but was
      unrelated to cortisol response to the stressor. Regardless of mindfulness,
      greater depressive/anxiety symptoms related to a more blunted cortisol response.
      Mindfulness might promote better distress tolerance in adolescents at risk for
      diabetes by altering how youth perceive and relate to acute stress, rather than
      through altering the physiological stress response. At all levels of mindfulness,
      depressive/anxiety symptoms relate to greater blunting of cortisol response.
      Findings contribute to emerging literature on the role of mindfulness in
      promoting the mental and physical health and well-being of individuals at risk
      for Type 2 diabetes.

PMID- 30100697
TI  - Good and Bad Sides of Self-Compassion: A Face Validity Check of the Self
      Compassion Scale and an Investigation of its Relations to Coping and Emotional
      Symptoms in Non-Clinical Adolescents.
AB  - To demonstrate that the positive and negative subscales of Self-Compassion Scale
      (SCS) are very different in nature, we conducted a series of face validity checks
      on the items of this questionnaire among psychologists and psychology students
      (Study 1). Furthermore, a survey was administered to a convenience sample of non
      clinical adolescents to examine the relations between various SCS subscales and
      symptoms of anxiety and depression as well as coping styles (Study 2). The
      results of the face validity checks revealed that the positive subscales seem to
      be well in line with the protective nature of self-compassion as they were mainly
      associated with cognitive coping and healthy functioning, whereas the negative
      subscales were chiefly associated with psychopathological symptoms and mental
      illness. The survey data demonstrated that the positive SCS subscales were
      positively correlated with adaptive coping (r's between .22 and .50) and
      negatively correlated with symptoms of anxiety and depression (r's between -.19
      and -.53), while the negative subscales were positively correlated with symptoms
      (r's between .49 and .61) and maladaptive coping strategies such as passive
      reacting (r's between .53 and .56). Additional analyses indicated the negative
      subscales of the SCS accounted for a significant proportion of the variance in
      symptoms, whereas the unique contribution of the positive SCS subscales was
      fairly marginal. We caution to employ the total SCS score that includes the
      reversed negative subscales as such a procedure clearly inflates the relation
      between self-compassion and psychopathology.

PMID- 30100699
TI  - Home Is Where the Hearth Is: Anthracological and Microstratigraphic Analyses of
      Pleistocene and Holocene Combustion Features, Riwi Cave (Kimberley, Western
      Australia).
AB  - The manipulation of fire is a technological act. The identification of the
      archaeological signatures of the controlled use of fire has important
      implications not only for the estimations of the origins and functions of the
      first fireplaces but also for our understanding of prehistoric technological
      development and resource use. At Riwi (Kimberley region, Western Australia),
      excavations over two field seasons have revealed a discontinuous occupation
      sequence over the past 45 ka, showing numerous, different combustion features
      interspersed within the deposit. Anthracological and micromorphological
      investigations at Riwi Cave indicate that the combustion features at the site can
      be categorised into three types: flat combustion features (type A), dug
      combustion features (type B) and thick accumulations of mixed combustion residues
      (type C). These provide evidence for two kinds of combustion practice: (i) fires
      lit directly on the ground and most likely not re-used and (ii) ground ovens, the
      latter appearing some 10,000 years after the first evidence for occupation of the
      site. A comparison of the wood species identified within these combustion
      features with those from equivalent scattered context levels, enables an
      exploration of the potential factors influencing wood selection and fire use
      through time at the site. A detailed understanding of the relationship between
      wood charcoal remains and archaeological context yields significant information
      on changes to environmental context and site occupation patterns over time.

PMID- 30100698
TI  - Addressing Barriers to Recruitment and Retention in the Implementation of
      Parenting Programs: Lessons Learned for Effective Program Delivery in Rural and
      Urban Areas.
AB  - Research has demonstrated the effectiveness of family-based programs for reducing
      adolescent risk behaviors and promoting adolescent health; however, parent
      engagement, specifically in terms of recruitment and retention, remains a
      consistent challenge. Recruitment rates for family-based prevention programs
      range from 3 to 35%, while, on average, 28% of caregivers drop out before program
      completion. Thus, engagement of parents in prevention programming is of utmost
      concern to ensure families and youth benefit from implementation of family-based
      programs. In this manuscript, two Centers for Disease Control and Prevention
      funded projects share their experiences with engagement of parents in violence
      prevention programs. Problems related to parent engagement are reviewed, as are
      structural, attitudinal, and interpersonal barriers specific to recruitment and
      retention. Examples of successful implementation strategies identified across
      urban and rural sites are also analyzed and lessons learned are provided.

PMID- 30100700
TI  - A Sensory Update to the Chaine Operatoire in Order to Study Skill: Perceptive
      Categories for Copper-Compositions in Archaeometallurgy.
AB  - This paper introduces the methodology of perceptive categories through which an
      empirical analysis of skill is achievable, taking European Bronze Age
      metalworking as a case study. Based on scientific data provided by the material
      sciences, in this case compositional and metallographic analyses of Late Copper
      Age and Early Bronze Age axes, the thresholds to categorise and interpret these
      data, and organise them in a chaine operatoire, are centred on the human senses
      and thus on metalworking as a craft. This is a pragmatic approach that
      appreciates scientific measurements of metal objects as essential empirical
      evidence whilst recognising that a considerable share of these archaeometric data
      are inapt or too detailed for an understanding of skill. This empirical approach
      towards skill is relevant to our knowledge of the role of crafts and materials in
      the past. After all, skill is a fundamental asset for the production of material
      culture, and a distinct human-material relationship characterised by an intimate
      form of material engagement.

PMID- 30100701
TI  - The Continuing Evolution of Ethical Standards for Genomic Sequencing in Clinical
      Care: Restoring Patient Choice.

PMID- 30100703
TI  - Requirement of longer term antiviral therapy in patients with cytomegalovirus
      anterior uveitis with corneal endothelial cell damage.
AB  - Background: The aim of the study was to investigate the efficacy of therapy in
      patients with cytomegalovirus (CMV) anterior uveitis. Patients and methods: We
      reviewed the records of patients with CMV anterior uveitis who attended our
      institution between October 2010 and December 2015 and who were confirmed to have
      CMV DNA in the aqueous humor by polymerase chain reaction analysis. Results:
      Fourteen immunocompetent patients (10 men and 4 women, total of 17 eyes) were
      enrolled. The mean +/- SD age at the onset of antiviral therapy was 63.1 +/- 11.3
      years (range, 44-87 years). CMV DNA was not detected in the aqueous humor of 3
      patients on initial testing, but it was detected on subsequent analysis. All
      patients underwent systemic antiviral therapy. Among the patients who were
      followed up for more than 6 months after starting systemic antiviral therapy,
      systemic antiviral therapy was successfully terminated in all 4 patients without
      corneal endothelial loss but had to be continued because of disease recurrence on
      its termination in 5 of 8 patients (62.5%) with corneal endothelial damage (P =
      0.038). Conclusions: Patients with corneal endothelial cell loss are likely to
      require longer term antiviral therapy than those without endothelial damage. In
      addition, whereas definitive diagnosis of CMV anterior uveitis requires the
      detection of CMV DNA in aqueous humor by polymerase chain reaction, one-fifth of
      patients in the present study tested negative on initial examination.

PMID- 30100702
TI  - Eyewitness Identification: Live, Photo, and Video Lineups.
AB  - The medium used to present lineup members for eyewitness identification varies
      according to the location of the criminal investigation. Although in some
      jurisdictions live lineups remain the default procedure, elsewhere this practice
      has been replaced with photo or video lineups. This divergence leads to two
      possibilities: Either some jurisdictions are not using the lineup medium that
      best facilitates accurate eyewitness identification or the lineup medium has no
      bearing on the accuracy of eyewitness identification. Photo and video lineups are
      the more practical options, but proponents of live lineups believe witnesses make
      better identification decisions when the lineup members are physically present.
      Here, the authors argue against this live superiority hypothesis. To be superior
      in practice, the benefits of live presentation would have to be substantial
      enough to overcome the inherent difficulties of organizing and administering a
      live lineup. The review of the literature suggests that even in experimental
      settings, where these difficulties can be minimized, it is not clear that live
      lineups are superior. The authors conclude that live lineups are rarely the best
      option in practice and encourage further research to establish which nonlive
      medium provides the best balance between probative value and practical utility.

PMID- 30100704
TI  - Clinical outcomes following trifocal diffractive intraocular lens implantation
      for age-related cataract in China.
AB  - Purpose: The aim of this study was to evaluate visual, refractive and patient
      satisfaction outcomes following implantation of a trifocal diffractive
      intraocular lens (IOL). Patients and methods: This prospective, consecutive study
      included patients undergoing lens phacoemulsification of cataract and
      implantation of a trifocal diffractive IOL (AT LISA tri 839MP). Visual outcomes,
      including near, intermediate and distance visual acuity (VA), refractive error,
      contrast sensitivity, defocus curve and patient satisfaction were assessed
      preoperatively and postoperatively. Results: Thirty IOLs were implanted in 26
      patients. Distance VA improved significantly from 0.70+/-0.45 to 0.08+/-0.11
      logMAR (p<0.0001) 1 week postoperatively, and to 0.07+/-0.13 logMAR (p<0.0001) at
      1 month and 0.05+/-0.10 logMAR (p<0.0001) at 3 months. Uncorrected near and
      intermediate VA, as well as corrected near, intermediate and distance VA, were
      stable and maintained during the follow-up period. Preoperative anterior chamber
      depth demonstrated an association with effective adjustment of postoperative
      spherical equivalent using a regression formula (p=0.007). No significant
      differences were observed for VA at defocus curves of 0 to -3 D. Contrast
      sensitivity at each spatial frequency improved significantly at 1 week, 1 month
      and 3 months under photopic and photopic with glare conditions. Under mesopic and
      mesopic with glare conditions, significant differences were observed
      postoperatively at low and medium spatial frequencies. Patients reported a high
      level of satisfaction and an absence of glare or halo 3 months postoperatively.
      Conclusion: In this study, the trifocal diffractive IOL provided excellent visual
      performance at all distances and improved contrast sensitivity under different
      conditions, resulting in high levels of patient satisfaction and spectacle
      independence in Chinese patients.

PMID- 30100706
TI  - Care pathways and treatment patterns for patients with heart failure in China:
      results from a cross-sectional survey.
AB  - Purpose: The objective of this study was to describe the clinical care pathways,
      management and treatment patterns, and hospitalizations for patients with heart
      failure (HF) in China. Subjects and methods: A cross-sectional survey of
      cardiologists and their patients with HF was conducted. Patient record forms were
      completed by 150 cardiologists for 10 consecutive patients. Patients for whom a
      patient record form was completed were invited to complete a patient self
      completion questionnaire. Results: Most of the 1,500 patients (mean [SD] age 66
      [10] years; 55% male) included in the study received care in tier-2 and -3
      hospitals in large cities. Cardiologists were responsible for initial
      consultation, diagnosis, and treatment of patients with HF. The use of guideline
      recommended diagnostics was high. However, guideline-recommended double- and
      triple-combination therapy was received by only 51% and 18% of patients,
      respectively. In total, 20% of patients with HF reported that they were not
      consulted on the choice of therapy. Concordance was high (>=80%) between matched
      cardiologist and patient pairs for the occurrence of side effects, while
      cardiologists more often under- than overreported the occurrence of side effects
      of treatment reported by patients. Conclusion: The management of HF was
      predominantly overseen by cardiologists. The use of diagnostic tests was high,
      but the use of guideline-recommended treatment was low in this population.
      Improved communication between patients and cardiologists is essential to
      optimize treatment decision making and to increase awareness of treatment side
      effects.

PMID- 30100705
TI  - Cone photoreceptor macular function and recovery after photostress in early non
      exudative age-related macular degeneration.
AB  - Purpose: To identify parameters from cone function and recovery after photostress
      that detect functional deficits in early non-exudative age-related macular
      degeneration (AMD) and to determine the repeatability of these parameters.
      Methods: Cone-mediated visual function recovery after photostress was examined in
      three groups of subjects: young normal subjects (ages 20-29; N=8), older normal
      subjects (ages 50-90; N=9), and early non-exudative AMD subjects (ages 50-90;
      N=12). Eight AMD and four normal subjects were retested 1 year after the initial
      evaluation. Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity (VA)
      and parameters of cone function (baseline cone sensitivity and cone recovery half
      life following photobleach) were measured and compared between AMD and normal
      subjects. Short-term repeatability was assessed for each subject's initial
      evaluation. Long-term repeatability was assessed by comparing outcomes from the
      initial evaluation and 1-year follow-up. Results: The mean baseline cone
      threshold was significantly worse in subjects with early AMD compared to older
      normal subjects (-1.80+/-0.04 vs -1.57+/-0.06 log cd/m2p=0.0027). Moreover, the
      baseline cone threshold parameter exhibited good short-term (intraclass
      correlation coefficient [ICC]=0.88) and long-term (ICC=0.85) repeatability in all
      subjects. The cone intercept parameter and ETDRS VA were not significantly
      different between AMD and older normal subject groups. Cone recovery half-life
      was significantly different between older normal and AMD subject groups
      (p=0.041). Neither ETDRS VA nor cone function parameters were significantly
      different for any group at the 1-year follow-up. Conclusion: The baseline cone
      threshold shows potential as a novel parameter to assess visual dysfunction in
      early AMD. This outcome consistently detected deficits in AMD subjects, and
      differentiated them from age-matched controls with high test-retest
      repeatability.

PMID- 30100708
TI  - Glaucoma, dementia, and the "precipice of care": transitions between states of
      medication adherence.
AB  - Purpose: "She wouldn't remember. Even when I go through, and she's decided to go
      to bed, I'll say I'll come and do her drops. If I didn't say that, they wouldn't
      be done." Dementia is widely considered as a key factor in whether patients take
      their medication as prescribed. However, few studies have examined the effect of
      dementia on medication management strategies for glaucoma including how patient
      and carer needs impact adherence and long-term prognosis. We report findings from
      a qualitative grounded theory study incorporating the views of patients, carers,
      and healthcare professionals. Methods: Eighty-three semistructured interviews
      were conducted with 35 patients, 22 lay carers, and nine healthcare professionals
      across sites in Wales and Scotland. These explored understanding of eye drop
      regimens, barriers, and facilitators to drop administration, as well as attitudes
      toward glaucoma, dementia, and other comorbidities. Results: Using Pound's
      synthesis of adherence behavior, we identified categories of active and passive
      acceptance of medicines, alongside modification or rejection of eye drop
      regimens. In relation to dementia, participants highlighted transitions between
      such categories, with a shift from active to passive acceptance commonly
      reported. This loss of self-medicating capability was referred to as the
      precipice of care, where entwinement of multiple conditions (eg, heart disease,
      glaucoma, and dementia) and sociocultural influences (eg, living alone)
      contributed to accelerated health declines. That said, numerous factors mitigated
      this, with a key role being the lay carer. Spouses and family members often acted
      as the monitor of eye drops for patients, seeking intervention when any
      behavioral changes influenced their administration. Conclusion: Though dementia
      was associated with progression toward the precipice of care, factors such as
      communication with healthcare professionals appeared to affect patient adherence.
      Recommendations for healthcare practice include better recording of dementia
      diagnoses and integrating eye drops into preexisting routines.

PMID- 30100707
TI  - Role of janus kinase inhibitors in the treatment of alopecia areata.
AB  - Alopecia areata (AA) is a common hair loss disorder worldwide with characteristic
      exclamation mark hairs. Although AA is self-limited, it can last for several
      months or even years in some patients. Currently, there is no US Food and Drug
      Administration-approved treatment for AA. Many off-label treatments are available
      but with limited efficacy. Through a better understanding of molecular biology,
      many targeted therapies have emerged as new alternatives for various autoimmune
      diseases. Various janus kinase (JAK) and signal transducer and activator of
      transcription (STAT) proteins form signaling pathways, which transmit
      extracellular cytokine signals to the nucleus and induce DNA transcriptions. By
      inhibiting JAK, T-cell-mediated inflammatory responses are suppressed. Increasing
      evidence suggests that JAK inhibitors (JAKis) are effective in the treatment of
      many autoimmune diseases, including AA. Among these, several studies on
      tofacitinib, ruxolitinib, and baricitinib in AA had been published, demonstrating
      promising outcomes of these agents. Unlike oral formulations, efficacy of topical
      forms of tofacitinib and ruxolitinib reported in these studies is still
      unsatisfactory and requires improvement. This review aims to summarize evidence
      of the efficacy and safety of JAKis in the treatment of AA.

PMID- 30100709
TI  - A pilot study of observed physician-parent-child communication and child
      satisfaction in a gastroenterology clinic.
AB  - Background: Child participation in pediatric medical visits is low. In this pilot
      study, we sought to better understand relationships between observed
      communication and child-reported perceptions of communication in a clinical
      setting. Materials and methods: For this cross-sectional observational study,
      pediatric gastroenterology appointments (n=39) were videotaped and coded to
      quantify various adult affective (eg, chit-chat, empathy) and facilitative (eg,
      asking questions, encouraging responses) behaviors toward the child, interference
      with child participation (eg, interrupting or ignoring child), and child verbal
      participation. Post-visit surveys assessed child perceptions of having voice in
      the clinical encounter, ease of understanding, and satisfaction with
      communication. Results: Parent and provider chit-chat was associated with child
      reported ease of understanding. Provider facilitation was positively associated
      with child participation, but affective communication strategies were not.
      Physician interference was negatively associated with ease of understanding but
      positively associated with perception of voice. Conclusion: Facilitative
      communication may improve outcomes by enhancing child participation and thus
      exchange of medical information, whereas chit-chat appears to positively impact
      children's perceptions of communication.

PMID- 30100710
TI  - A spoonful of sugar helps the medicine go down? A review of strategies for making
      pills easier to swallow.
AB  - Solid oral dosage forms such as tablets and capsules are generally the preferred
      method of drug delivery due to their convenience, cost, and acceptability.
      However, for many people, it can be a challenge to swallow solid oral
      medications, even those with healthy swallowing function. This review describes
      current strategies available to facilitate medication administration to otherwise
      healthy people with pill-swallowing difficulties. In general, restoring and
      maintaining the ability to swallow pills whole should ideally be the first choice
      in managing people with pill-swallowing difficulties. A number of strategies can
      potentially make it easier to swallow pills whole. These include postural
      adjustments, using pill-swallowing aids, and teaching pill-swallowing techniques.
      Where these are not successful or appropriate, then other approaches have to be
      considered using alternative formulations/routes of administration or
      deprescribing. If there is no other option, and it is not directly
      contraindicated for each specific medication dosage form, pills may be modified
      and mixed in foods and drinks to aid swallowing. In conclusion, people with pill
      swallowing difficulties can benefit from a number of strategies designed to
      facilitate swallowing medications. However, these strategies should be further
      evaluated with regard to the evidence relating to both their efficacy and safety.

PMID- 30100711
TI  - Health-related quality of life in elderly diabetic outpatients in Vietnam.
AB  - Background: Health-related quality of life (HRQoL) is an important indicator for
      designing care and treatment services for patients with diabetes. This is
      especially true given its rapid increase among the elderly population in Vietnam.
      HRQoL data in elderly diabetic Vietnamese are currently limited. This study aimed
      to 1) measure the HRQoL of elderly patients with type 2 diabetes (T2DM) in
      Vietnam and 2) identify related factors and their relationship with HRQoL.
      Patients and methods: A cross-sectional study was conducted. We recruited 171
      patients aged >=60 years with T2DM at the Outpatient Department, National
      Geriatric Hospital from June to November 2015. Patients were asked to evaluate
      their health status using the EuroQol Five Dimensions Three Levels (EQ-5D-3L) and
      the Visual Analog Scale (VAS). Sociodemographic, diabetic treatment, and
      management characteristics were collected. Multivariate Tobit regression was used
      to determine which factors were associated with HRQoL, and the strength of this
      relationship. Results: Patients reported some problems in all areas of the EQ-5D:
      pain/discomfort (50.9%), mobility (33.3%), anxiety/depression (24.0%), usual
      activities (21.1%), and self-care (10.5%). The mean EQ-5D index score was 0.80
      (SD=0.20), and the mean EQ-VAS was 57.5 (SD=14.4). Patients who were male, lived
      in an urban area, could afford treatment, were taking fewer medications, and
      monitored blood pressure often (1-4 times a week) had a higher EQ-5D index when
      compared to other groups. Meanwhile, a longer duration of diabetes and older age
      were negatively associated with the EQ-5D index. Patients with any comorbidity
      had lower VAS scores than their counterparts. Conclusion: The presence of
      diabetes and comorbidity were responsible for a significant decrease in HRQoL.
      Screening and identifying health problems, providing prompt treatment, and
      facilitating self-management among patients have the potential to increase
      diabetic patients' HRQoL.

PMID- 30100712
TI  - Bipolar disorder and adherence: implications of manic subjective experience on
      treatment disruption.
AB  - Objective: Therapeutic observance is one of the cornerstones of bipolar disease
      prognosis. Nostalgia of previous manic phase has been described as a cause of
      treatment retrieval in bipolar disorder. But to date no systematic study has
      examined manic episode remembering stories. Our aim was to describe manic
      experience from the patient's point of view and its consequences on subjective
      relation to care and treatment adherence. Patients and methods: Twelve euthymic
      patients with bipolar I disorder were interviewed about their former manic
      episodes and data was analyzed, thanks to a grounded theory method. Results:
      Nostalgia was an anecdotal reason for treatment retrieval in bipolar I disease.
      Although the manic experience was described as pleasant in a certain way, its
      consequences hugely tarnish the memory of it afterward. Treatment interruption
      appears to be mostly involuntary and state-dependent, when a euphoric subject
      loses insight and does not see any more benefit in having treatment. Conclusion:
      Consciousness destructuring associated with mood elation should explain treatment
      disruption in bipolar I patients more than nostalgia. Taking a manic episode
      story into account may help patients, family, and practitioners to achieve better
      compliance by improving their comprehension and integration of this unusual
      experience.

PMID- 30100714
TI  - Erratum: Factors associated with appropriate inhaler use in patients with COPD -
      lessons from the REAL survey [Erratum].
AB  - [This corrects the article on p. 695 in vol. 13, PMID: 29520137.].

PMID- 30100713
TI  - The association of therapeutic versus recreational marijuana use and
      antiretroviral adherence among adults living with HIV in Florida.
AB  - Purpose: Marijuana use is common among people living with HIV (PLWH), but its
      association with antiretroviral therapy (ART) adherence is unclear. This study
      examined the association between reason for marijuana use and ART adherence in a
      sample of adults living with HIV. Patients and methods: Participants (N=703)
      recruited from seven community health centers in Florida completed a 45-minute
      questionnaire assessing demographics, symptoms of anxiety and depression, ART
      adherence, and substance use, including reasons for marijuana use. ART adherence
      was defined as the proportion of days in the last 30 days participants did not
      miss any medication and dichotomized as optimal (>=95%) and suboptimal (<95%).
      Multivariate logistic regression analysis assessed the association between
      therapeutic marijuana use to manage HIV symptoms (ie, improve appetite/gain
      weight, induce sleep, relieve nausea/vomiting, relieve pain, relieve
      anxiety/depression/stress) versus recreational marijuana use and ART adherence.
      Results: Approximately one third (33.2%) of the participants reported using
      marijuana in the past 3 months. Of marijuana users, 21.8% reported using
      marijuana only for therapeutic purposes to manage HIV-associated medical
      symptoms, while 78.2% reported recreational use. After controlling for
      covariates, therapeutic use of marijuana was not associated with ART adherence
      (AOR =1.19, 95% CI =0.60-2.38, p=0.602) while recreational marijuana users showed
      significantly greater odds of suboptimal ART adherence compared to nonusers (AOR
      =1.80, 95% CI =1.18-2.72, p=0.005). Conclusion: Our results suggest differences
      in ART adherence between individuals who report recreational versus therapeutic
      marijuana use. Continued research examining the health implications of marijuana
      use among adults living with HIV is important as legalization of recreational and
      medical marijuana proliferates in the United States.

PMID- 30100715
TI  - Identification of novel target genes in human lung tissue involved in chronic
      obstructive pulmonary disease.
AB  - Introduction: As part of a study aimed at illuminating at least some of the
      complex molecular events taking place in COPD, we screened tissues by means of
      transcriptome analyses. Materials and methods: Tissues were subjected to
      transcriptome analysis. Candidate genes were identified and validated by
      immunohistochemistry. Primary human lung cells were subjected to stimulation with
      cigarette smoke extract for further validation by real time PCR. Results: Six
      candidate genes were selected for further investigations: Aquaporin 3 (AQP3),
      extracellular matrix protein 1 (ECM1), four and a half LIM domain 1 (FHL1), milk
      fat globule epidermal growth factor 8 (MFGE8, lactadherin), phosphodiesterase 4D
      interacting protein (PDE4DIP), and creatine transporter SLC6A8. All six proteins
      were allocated to distinct cell types by immunohistochemistry. Upon stimulation
      with cigarette smoke extract, human type II pneumocytes showed a dose-dependent
      down-regulation of MFGE8, while ECM1 and FHL1 also tended to be down-regulated.
      Although present, none of the candidates was regulated by cigarette smoke extract
      in primary human macrophages. Discussion: MFGE8 turned out to be an interesting
      new candidate gene in COPD deserving further studies.

PMID- 30100716
TI  - Impact of BMI on exacerbation and medical care expenses in subjects with mild to
      moderate airflow obstruction.
AB  - Background and objective: The rate of obesity is increasing in Asia, but the
      clinical impact of body mass index (BMI) on the outcome of chronic obstructive
      pulmonary disease (COPD) remains unknown. We aimed to assess this impact while
      focusing on the risk of exacerbation, health-care utilization, and medical costs.
      Methods: We examined 43,864 subjects registered in the Korean National Health and
      Nutrition Examination Survey (KNHANES) database from 2007 to 2012, and linked the
      data of COPD patients who had mild to moderate airflow obstruction (n = 1,320) to
      National Health Insurance (NHI) data. COPD was confirmed by spirometry. BMI was
      used to stratify patients into four categories: underweight (BMI <18.5 kg/m2),
      normal range (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>=25
      kg/m2). Results: Of the 1,320 patients with COPD with mild to moderate airflow
      obstruction, 27.8% had a BMI >=25 kg/m2. Compared with normal-weight patients,
      obese patients tended to experience fewer exacerbations (incidence rate ratio
      [IRR] 0.88; 95% CI 0.77-0.99; P = 0.04), although this association was not
      significant in a multivariable analysis. COPD-related health-care utilization and
      medical expenses were higher among underweight patients than the other groups.
      After adjustment, the risk of COPD-related hospitalization was highest among
      underweight and higher among overweight patients vs normal-weight patients
      (adjusted IRRs: 7.12, 1.00, 1.26, and 1.02 for underweight, normal, overweight,
      and obese groups, respectively; P = 0.01). Conclusion: Decreased weight tends to
      negatively influence prognosis of COPD with mild to moderate airflow obstruction,
      whereas higher BMI was not significantly related to worse outcomes.

PMID- 30100717
TI  - The use of a standardized order set reduces systemic corticosteroid dose and
      length of stay for individuals hospitalized with acute exacerbations of COPD: a
      cohort study.
AB  - Background: Systemic corticosteroids (SC) are an integral part of managing acute
      exacerbations of COPD (AECOPD). However, the optimal dose and duration vary
      widely in clinical practice. We hypothesized that the use of a "PowerPlan" order
      set in the electronic health system (EHS) that includes a 5-day SC order would be
      associated with a reduced steroid dose and length of stay (LOS) for individuals
      hospitalized with AECOPD. Patients and methods: We conducted a retrospective
      cohort study of Medicare recipients discharged with an AECOPD diagnosis from our
      University Hospital from 2014 to 2016. Our EHS-based "COPD PowerPlan" order set
      included admission, laboratory, pharmacy, and radiology orders for managing
      AECOPD. The default SC option included intravenous methyl-prednisolone for 24
      hours followed by oral prednisone for 4 days. The primary endpoint was the
      difference in cumulative steroid dose between the PowerPlan and the usual care
      group. Secondary endpoints included hospital LOS and readmission rates. Results:
      The 250 patients included for analysis were 62+/-11 years old, 58% male, with an
      FEV1 55.1%+/-23.6% predicted. The PowerPlan was used in 72 (29%) patients.
      Cumulative steroid use was decreased by 31% in the PowerPlan group (420+/-224 vs
      611+/-462 mg, P<0.001) when compared with usual care. PowerPlan use was
      independently associated with decreased LOS (3 days; IQR 2-4 days vs 4 days; IQR
      3-6 days, P=0.022) without affecting 30- and 90-day readmission rates.
      Conclusion: Use of a standardized EHS-based order set to manage AECOPD was
      associated with a reduction in steroid dose and hospital LOS.

PMID- 30100718
TI  - Determinants of medical prescriptions for COPD care: an analysis of the EPOCONSUL
      clinical audit.
AB  - Purpose: Current COPD management recommendations indicate that pharmacological
      treatment can be stepped up or down, but there are no recommendations on how to
      make this adjustment. We aimed to describe pharmacological prescriptions during a
      routine clinical visit for COPD and study the determinants of changing therapy.
      Methods: EPOCONSUL is a Spanish nationwide observational cross-sectional clinical
      audit with prospective case recruitment including 4,508 COPD patients from
      outpatient respiratory clinics for a period of 12 months (May 2014-May 2015).
      Prescription patterns were examined in 4,448 cases and changes analyzed in
      stepwise backward, binomial, multivariate, logistic regression models. Results:
      Patterns of prescription of inhaled therapy groups were no treatment prescribed,
      124 (2.8%) cases; one or two long-acting bronchodilators (LABDs) alone, 1,502
      (34.6%) cases; LABD with inhaled corticosteroids (ICSs), 389 (8.6%) cases; and
      triple therapy cases, 2,428 (53.9%) cases. Incorrect prescriptions of inhaled
      therapies were observed in 261 (5.9%) cases. After the clinical visit was
      audited, 3,494 (77.5%) cases did not modify their therapeutic prescription, 307
      (6.8%) cases had a step up, 238 (5.3%) cases had a change for a similar scheme,
      182 (4.1%) cases had a step down, and 227 (5.1%) cases had other nonspecified
      change. Stepping-up strategies were associated with clinical presentation
      (chronic bronchitis, asthma-like symptoms, and exacerbations), a positive
      bronchodilator test, and specific inhaled medication groups. Stepping down was
      associated with lung function impairment, ICS containing regimens, and
      nonexacerbator phenotype. Conclusion: The EPOCONSUL study shows a comprehensive
      evaluation of pharmacological treatments in COPD care, highlighting strengths and
      weaknesses, to help us understand how physicians use available drugs.

PMID- 30100719
TI  - Optimization of molecularly targeted MRI in the brain: empirical comparison of
      sequences and particles.
AB  - Background: Molecular MRI is an evolving field of research with strong
      translational potential. Selection of the appropriate MRI sequence, field
      strength and contrast agent depend largely on the application. The primary aims
      of the current study were to: 1) assess the sensitivity of different MRI
      sequences for detection of iron oxide particles in mouse brain; 2) determine the
      effect of magnetic field strength on detection of iron oxide particles in vivo;
      and 3) compare the sensitivity of targeted microparticles of iron oxide (MPIO) or
      ultra-small superparamagnetic iron oxide (USPIO) for detection of vascular cell
      adhesion molecule-1 (VCAM-1) in vivo. Methods: Mice were injected intrastriatally
      with interleukin 1beta to induce VCAM-1 expression on the cerebral vasculature.
      Subsequently, animals were injected intravenously with either VCAM-MPIO or VCAM
      USPIO and imaged 1 or 13 hours post-injection, respectively. MRI was performed at
      4.7, 7.0, or 9.4 T, using three different T2*-weighted sequences: single gradient
      echo 3D (GE3D), multi-gradient echo 3D (MGE3D) and balanced steady-state free
      precession 3D (bSSFP3D). Results: MGE3D yielded the highest signal-to-noise ratio
      (SNR) and contrast-to-noise ratio (CNR) for the detection of iron oxide
      particles. All sequences showed a significant increase in SNR and CNR from 4.7 to
      7.0 T, but no further improvement at 9.4 T. However, whilst targeted MPIO enabled
      sensitive detection of VCAM-1 expression on the cerebral vasculature, the long
      half-life (16.5 h vs 1.2 min) and lower relaxivity per particle (1.29*10-14 vs
      1.18*10-9 Hz L/particle) of USPIO vs. MPIO rendered them impractical for
      molecular MRI. Conclusion: These findings demonstrate clear advantages of MPIO
      compared to USPIO for molecularly-targeted MRI, and indicate that the MGE3D
      sequence is optimal for MPIO detection. Moreover, higher field strengths (7.0/9.4
      T) showed enhanced sensitivity over lower field strengths (4.7 T). With the
      development of biodegradable MPIO, these agents hold promise for clinical
      translation.

PMID- 30100720
TI  - Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles
      for doxorubicin delivery.
AB  - Introduction: A reduction-sensitive CD44-positive tumor-targetable drug delivery
      system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)
      grafted polymers. Materials and methods: HA was conjugated with folic acid (FA)
      via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss
      FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy,
      Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance (NMR)
      spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance
      gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles
      were prepared and characterized. The reduction responsibility, cellular uptake,
      and in vivo biodistribution of HA-ss-FA micelles were investigated. Results: DOX
      loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading
      content (22.70%), appropriate mean diameter (100-120 nm), narrow size
      distribution, and negative zeta potential (-6.7 to -31.5 mV). The DOX release
      from the micelles was significantly enhanced in reduction environment compared to
      normal environment. The result of in vitro cytotoxicity assay indicated that the
      blank micelles were of low toxicity and good biocompatibility and the cell
      viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00
      MUg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX
      loaded micelles were tumor-targetable and could significantly enhance cellular
      uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in
      CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells.
      In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in
      vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded
      micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor
      bearing nude mice. Conclusion: HA-ss-FA is a promising nanocarrier with excellent
      biocompatibility, tumor targetability, and controlled drug release capability for
      delivery of chemotherapy drugs in cancer therapy.

PMID- 30100721
TI  - Folic acid-conjugated mesoporous silica nanoparticles for enhanced therapeutic
      efficacy of topotecan in retina cancers.
AB  - In this study, topotecan-loaded mesoporous silica nanoparticles were prepared and
      surface conjugated with folic acid (FTMN) to enhance the therapeutic efficacy of
      topotecan for the treatment of retinoblastoma (RB) cancers. The particles were
      nano-sized and exhibited a sustained release of drug in the physiological
      conditions. The folic acid-conjugated nanoformulations exhibited a remarkable
      uptake in RB cells compared to that of non-targeted nanoparticles. These results
      clearly indicate that receptor-mediated endocytosis is the mechanism of cellular
      internalization. The greater cellular uptake of FTMN resulted in significantly
      higher cytotoxic effect in Y79 cancer cells compared to that of other
      formulations. The results were well corroborated with the live/dead assay and
      nuclear fragmentation assay. FTMN consistently induced apoptosis of cancer cells
      with an efficiency of ~58%. Our results clearly showed that nanoparticulate
      encapsulation of TPT exhibited superior anticancer efficacy in Y79 cancer cells
      compared to that of free drug or non-targeted nanoparticles. As expected, FTMN
      exhibited a remarkable reduction in the overall tumor volume compared to any
      other group with less presence of tumor cells in histology staining. Overall,
      folic acid-conjugated nanoparticulate system could provide an effective platform
      for RB treatment.

PMID- 30100723
TI  - Attention-deficit hyperactivity disorder and impulsivity in female patients with
      fibromyalgia.
AB  - Objective: Data which indicate a greater role of the central nervous system in
      the etiology of fibromyalgia are increasing. The goal of the present study is to
      determine the link between fibromyalgia and attention-deficit hyperactivity
      disorder (ADHD) and, in addition, to reveal the relevance of impulsivity
      dimension. Methods: The study included 78 females with fibromyalgia who applied
      to a physical medicine and rehabilitation polyclinic in Ceyhan State Hospital and
      54 healthy females. The diagnosis of fibromyalgia was made by an experienced
      specialist of physical medicine and rehabilitation based on the American
      Rheumatology Association Diagnostic Criteria (2010). The diagnosis of ADHD was by
      an experienced psychiatrist using Diagnostic and Statistical Manual of Mental
      Disorders-5. The following inventories were used: adult ADHD self-report scale,
      Wender Utah rating scale, and Barratt impulsivity scale short form. Results:
      Adult ADHD was detected in 29.5% of the fibromyalgia group and 7.4% of the
      control group; childhood and adolescent attention hyperactivity disorder ratios
      in these groups were 33.3% and 11.1%, respectively. The differences were
      statistically significant (P=0.002, P=0.003). Scores of the fibromyalgia group on
      the Wender Utah rating scale, adult ADHD self-report scale, attention subscale,
      hyperactivity-impulsivity subscale, and the Barratt impulsivity scale for non
      planning and attentional impulsivity were found to be significantly higher than
      the control group (P<0.05, P<0.01, P<0.01, P<0.05, P<0.01, P<0.05, respectively).
      Conclusion: The present study has shown that both adult and childhood ADHD are
      quite common in female fibromyalgia patients. There was a link between
      fibromyalgia and impulsivity. Certain subtypes of fibromyalgia and attention
      deficit hyperactivity deficit disorder could be sharing the common etiological
      pathways.

PMID- 30100722
TI  - Rho GTPases in A549 and Caco-2 cells dominating the endocytic pathways of
      nanocarbons with different morphologies.
AB  - Introduction: Endocytosis of nanomaterials is the first step of nano-bio
      interaction and current regulation is mostly by nanomaterials but seldom by
      intracellular signaling proteins. Materials and methods: Herein, we synthesized
      tubular nanocarbon (oxMWCNT) and lamellar-like nanocarbon (oxGRAPHENE) and
      formulated their aqueous dispersion. A549 and Caco-2 cells were selected as the
      models of tumor and intestinal epithelial cells, respectively. After knocking
      down three members of Rho GTPases (Cdc42, Rac1, RhoA) in these two cell lines,
      their silencing effects on the uptake pathways of nanomaterials with different
      morphologies were investigated. Results: An unexpected finding was that the knock
      down led to opposite uptake trends in different types of cells. The endocytosis
      of carbon nanomaterials increased in Caco-2 cells when Rho GTPases were
      inactivated, while that in A549 cells decreased. For nanomaterials with different
      shapes, the involved GTPase member of Rho family, or regulating protein molecule,
      was different. Concretely, Cdc42 and Rac1 were involved in oxMWCNT endocytosis,
      while all three GTPases participated in oxGRAPHENE internalization. More
      interestingly, such difference induced different uptake pathways, namely, the
      cellular uptake of oxMWCNT was clathrin-mediated and oxGRAPHENE was caveolin
      modulated, both with the involvement of dynamin. Conclusion: In conclusion, this
      study provides new insights for the potential intervention in nano-bio interplay.

PMID- 30100724
TI  - Profiling undergraduate students from a Romanian medical university.
AB  - Purpose: Medical students' personality traits, emotion regulation strategies, and
      empathic behavior are considered powerful predictors for their future
      achievements, professional adjustment, and mental strength. Coping strategies
      such as "self-blame," "rumination," "catastrophizing," "blaming others," lack of
      empathy, decreased emotion recognition abilities, and neuroticism are maladaptive
      and, thus, less desirable traits in medical professionals. The purpose of the
      study was to comparatively assess and find potential correlations between
      personality traits, empathy levels, emotion recognition abilities, and cognitive
      emotion regulation strategies of three medical student samples: general medicine
      (GM), dental medicine (DM), and general nursing (GN) students. Patients and
      methods: This cross-sectional comparative study was conducted throughout the
      second semester of 2017, during Psychiatry class, on 306 medical undergraduates
      of the "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania.
      Personality was assessed by using Neuroticism-Extraversion-Openness to Experience
      Five-Factor Inventory (NEO-FFI). Cognitive emotion regulation strategies were
      identified using the Cognitive Emotion Regulation Questionnaire (CERQ). Empathy
      quotient (EQ) was used to measure empathy levels. Emotion recognition abilities
      were evaluated with the Reading the Mind in the Eyes test (RMET). Results: GM
      students scored significantly higher than both DM and GN students in blaming
      others (CERQ) and significantly higher than GN students in "neuroticism" (NEO
      FFI). GM and DM students obtained significantly lower scores than their GN
      colleagues in "agreeableness" (NEO-FFI) and empathy (EQ). Compared to DM
      students, GN students gave significantly more correct answers in RMET.
      Neuroticism was associated with less efficient coping mechanisms (self-blame,
      rumination, catastrophizing, blaming others) and lower empathy scores. Empathy
      correlated negatively with blaming others and was positively associated with
      agreeableness and emotion recognition abilities. Conclusion: The differences
      found between the student samples can be consequences of several overlapping
      factors. Certain personality traits may predispose individuals to maladaptive
      coping responses, increased vulnerability to stress, and lower empathy levels.
      The results of this study can be viewed as baseline data for future, more
      comprehensive, longitudinal analyses.

PMID- 30100725
TI  - Identifying a subpopulation with higher likelihoods of early response to
      treatment in a heterogeneous rare disease: a post hoc study of response to
      teduglutide for short bowel syndrome.
AB  - Purpose: Teduglutide, a glucagon-like peptide-2 analog, has demonstrated efficacy
      in reducing parenteral support (PS) among patients with short bowel syndrome with
      intestinal failure (SBS-IF). This study aims to identify a subpopulation of SBS
      IF patients for whom teduglutide has an especially pronounced effect. Patients
      and methods: Data were from a 24-week, Phase III trial (Study of Teduglutide
      Effectiveness in Parenteral Nutrition-Dependent SBS Subjects; NCT00798967) that
      randomized SBS-IF patients with PS dependency to receive teduglutide (n=43) or
      placebo (n=43). Two prediction models (1 for each arm) were developed for
      response, defined as 20% reduction in weekly PS at Weeks 20 and 24. Potential
      predictors included demographics, disease characteristics, and concomitant
      medications. Patients were then ranked based on the effect score, an
      individualized predicted response rate difference with teduglutide versus
      placebo. A subpopulation of patients with a pronounced benefit from teduglutide
      versus placebo was identified. Baseline characteristics and clinical outcomes
      were compared between patients included versus those not included in the
      subpopulation. Results: Six predictors of response to teduglutide were selected:
      older age, volvulus as the cause of major intestinal resection, baseline PS
      volume >6 L per week, longer time since start of PS dependency, absence of
      ileocecal valve, and lower percentage of colon remaining. Higher percentage of
      colon remaining and volvulus were the selected predictors for response to
      placebo. A subpopulation of patients more likely to respond to teduglutide was
      identified as those with the top 60% effect scores. The difference in response
      rate between teduglutide and placebo was 62% in the subpopulation, which was
      substantially higher than the difference of 33% in the overall population. Mean
      PS day reduction was also significantly higher for teduglutide compared to
      placebo in the subpopulation. Conclusion: Pretreatment characteristics as
      predictors of response to teduglutide versus placebo within 24 weeks were
      identifiable in the clinical trial population of SBS-IF patients.

PMID- 30100726
TI  - The characteristics and risk factors for cisplatin-induced acute kidney injury in
      the elderly.
AB  - Objectives: The most serious adverse reaction of cisplatin is acute kidney injury
      (AKI). Cisplatin-induced acute kidney injury (CIA) has no specific preventive
      measures. This study aims to explore the characteristics and risk factors for CIA
      in the elderly and to identify potential methods to reduce CIA. Materials and
      methods: Patients >=18 years old, with primary tumors, who received initial
      cisplatin chemotherapy and whose serum creatinine (SCr) values were measured
      within 2 weeks pre- and postcisplatin treatment and who had complete medical
      records, were selected from a single center from January 1, 2013 to December 31,
      2015. The exclusion criteria included radiotherapy or surgery, recurrent tumors,
      previous cisplatin treatment, lack of any SCr values before or after cisplatin
      therapy, and incomplete medical records. Results: Out of a total of 527 patients,
      349 were elderly. Angiotensin-converting enzyme inhibitor/angiotensin receptor
      blocker (ACEI/ARB) use (9.2%) was more prevalent in the elderly than in younger
      patients (2.8%, p = 0.007). The dosage of cisplatin treatment was lower in the
      elderly, but the incidence of CIA (9.46%) was higher in the elderly than in
      younger patients (3.37%). There were significant differences in the SCr levels,
      estimated glomerular filtration rate, ACEI/ARB use, and whether a single
      application of cisplatin was administered, between the elderly AKI group and the
      non-AKI group. Multivariable analysis showed that administration of a single
      application of cisplatin (OR 2.853, 95% CI: 1.229, 6.621, p = 0.015) and ACEI/ARB
      use (OR 3.398, 95% CI: 1.352, 8.545, p = 0.009) were predictive factors for
      developing CIA in the elderly. Conclusion: The incidence of CIA in the elderly
      was higher than in younger patients. ACEI/ ARB usage and administration of a
      single application of cisplatin were independent risk factors for CIA in the
      elderly.

PMID- 30100727
TI  - Angiotensin II: a new therapeutic option for vasodilatory shock.
AB  - Angiotensin II (Ang II), part of the renin-angiotensin-aldosterone system (RAS),
      is a potent vasoconstrictor and has been recently approved for use by the US Food
      and Drug Administration in high-output shock. Though not a new drug, the recently
      published Angiotensin II for the Treatment of High Output Shock (ATHOS-3) trial,
      as well as a number of retrospective analyses have sparked renewed interest in
      the use of Ang II, which may have a role in treating refractory shock. We
      describe refractory shock, the unique mechanism of action of Ang II, RAS
      dysregulation in shock, and the evidence supporting the use of Ang II to restore
      blood pressure. Evidence suggests that Ang II may preferentially be of benefit in
      acute kidney injury and acute respiratory distress syndrome, where the RAS is
      known to be disrupted. Additionally, there may be a role for Ang II in
      cardiogenic shock, angiotensin converting enzyme inhibitor overdose, cardiac
      arrest, liver failure, and in settings of extracorporeal circulation.

PMID- 30100729
TI  - Predisposition of functional genetic variants of A-kinase anchoring protein 10
      toward acquired repolarization disorders in high-risk vascular surgery patients.
AB  - Purpose: We aimed at assessing the predisposition of A-kinase anchoring protein
      10 (AKAP10) polymorphism toward acquired repolarization disorders in high-risk
      vascular surgery patients. Patients and methods: One hundred adult patients (age
      =44-85 years), scheduled for an elective high-risk "open" vascular surgery
      procedure, were recruited. The electrocardiogram Holter monitor was used to
      assess repolarization stability from the beginning of the operation up to 24
      hours afterward. The AKAP10 gene rs203462 polymorphism and cardiac complications
      were analyzed. Results: Repolarization disturbances defined as QT interval
      duration corrected for heart rate (QTc) interval prolongation >500 ms and QTc
      interval dispersion >65 ms were recorded in 46 patients. A model of multivariate
      logistic regression showed that only the presence of allele G of the AKAP10
      polymorphism was an independent risk factor for repolarization disturbances in
      the perioperative period (odds ratio =14.35; 95% CI =4.65-44.23; p<0.0001).
      Conclusion: When the acquired QTc interval prolongation or QTc dispersion is
      associated with AKAP10 polymorphism, it may remain clinically silent.

PMID- 30100728
TI  - Dendritic cell vaccines for high-grade gliomas.
AB  - Glioblastoma (GBM) is the most common and fatal primary adult brain tumor. To
      date, various promising chemotherapeutic regimens have been trialed for use in
      GBM; however, temozolomide (TMZ) therapy remains the only US Food and Drug
      Administration-approved first-line chemotherapeutic option for newly diagnosed
      GBM. Despite maximal therapy with surgery and combined concurrent chemoradiation
      and adjuvant TMZ therapy, the median overall survival remains approximately 14
      months. Given the failure of conventional chemotherapeutic strategies in GBM,
      there has been renewed interest in the role of immunotherapy in GBM. Dendritic
      cells are immune antigen-presenting cells that play a role in both the innate and
      adaptive immune system, thereby making them prime vehicles for immunotherapy via
      dendritic cell vaccinations (DCVs) in various cancers. There is great enthusiasm
      surrounding the use of DCVs for GBM with multiple ongoing trials. In this review,
      we comprehensively summarize the safety, efficacy, and quality of life results
      from 33 trials reporting on DCV for high-grade gliomas.

PMID- 30100730
TI  - Farm-based day care in Norway - a complementary service for people with dementia.
AB  - Background: Day care services provide meaningful activities and coping
      experiences in a safe environment for people with dementia, as well as improve
      quality of life. Such services vary in types and settings. Farm-based day care
      (FDC) services are described as services that have been adapted from the farm
      setting, using farm resources to promote health. There is limited knowledge on
      the service offered in both FDC and regular day care services for people with
      dementia. The present study aims to investigate FDC in Norway and describe the
      services and the participants' care environment. Materials and methods: We mapped
      the existing farms offering day care in Norway by the spring 2017 (N=33) and
      collected information through two cross-sectional surveys (N=32) answered by the
      service providers at the farms. Results: The farms included in this survey
      provided day care services to 227 people with dementia, located in most regions
      of Norway. The services varied in terms of group size and half of the services
      had young people with dementia (<=65 years) and people with dementia at an early
      stage as their primary target group. About half of the staff had health care
      education (47.5%), and there were staff with agricultural competence available in
      most FDCs. All farms reported that the participants spent time outdoors every
      day, and all services, except two, had animals. The providers highlighted the
      opportunity to choose activities that were individually tailored for each
      participant, as the diversity of resources in the farm made it possible to
      organize different activities. Conclusion: FDC services have similarities in
      organization, daily structure, and number of health education personnel to other
      day care services, but differ in type of care environment with a wide range of
      activities and available resources like farm buildings, gardens, animals, and
      outdoor areas.

PMID- 30100731
TI  - Perceived control moderates the relationship between anxiety and in-hospital
      complications after ST segment elevation myocardial infarction.
AB  - Purpose: Anxiety is a common psychological response after acute myocardial
      infarction and might be associated with higher levels of in-hospital
      complications. Perceived control might moderate this relationship, but the effect
      of this method has not been checked in developing countries. Therefore, the
      objectives of this study were as follows: 1) to check if anxiety was an
      independent predictor of in-hospital complications after acute myocardial
      infarction; and 2) to check if perceived control moderates the relationship
      between anxiety and in-hospital complications after acute myocardial infarction.
      Patients and methods: This was a prospective observational study among 500
      patients with a confirmed diagnosis of ST segment elevation myocardial infarction
      recruited from three private hospitals in Amman, Jordan. Anxiety was measured by
      the Anxiety subscale of Hospital Anxiety and Depression Scale, and perceived
      control was measured by the Arabic version of the Control Attitude Scale-Revised.
      Results: One hundred and forty patients (28%) developed at least one complication
      during hospitalization. Two hundred and fifty-five patients had low anxiety
      scores (<=7), and 245 patients had high anxiety scores (>=8). Patients with high
      levels of perceived control had lower levels of anxiety (mean [SD]; 5.3 [3.6] vs
      14.1 [6.3], P<0.001) than those with low perceived control. In logistic
      regression, anxiety was an independent predictor of in-hospital complications
      after controlling for sociodemographic and clinical variables (odds ratio: 1.24,
      95% CI, 1.08-1.41, P<0.01). Moreover, the interaction of anxiety and perceived
      control was a significant predictor of complications. Conclusion: Anxiety was
      associated with increased risk of in-hospital complications after acute
      myocardial infarction independent of sociodemographic and clinical variables.
      Perceived control had a moderating effect for this association since the
      combination of low perceived control and high anxiety scores was associated with
      the greatest risk for complications. Supporting patients' levels of perceived
      control can decrease complications, morbidities, and mortality after acute
      myocardial infarction.

PMID- 30100732
TI  - Transcobalamin I: a novel prognostic biomarker of neoadjuvant chemotherapy in
      locally advanced hypopharyngeal squamous cell cancers.
AB  - Background: Hypopharyngeal squamous cell carcinoma (HPSCC) is an aggressive head
      and neck squamous cell carcinoma with poor prognosis. Neoadjuvant chemotherapy
      (NACT) followed by concurrent chemoradiotherapy could provide better efficacy in
      HPSCC treatment. Identification of predictive biomarkers is critically needed to
      improve selection of patients who derive the most benefit from NACT. The aim of
      this study was to investigate whether transcobalamin I (TCN1) could be a novel
      predictive biomarker for NACT in HPSCC. Methods: We collected biopsy specimens
      from 102 patients with primary locally advanced HPSCC. Messenger RNA (mRNA) and
      protein expression levels of TCN1 were analyzed using quantitative polymerase
      chain reaction and immunohistochemistry, respectively. The relationship between
      TCN1 expression, chemotherapy sensitivity, and clinical outcome was assessed
      using univariate Kaplan-Meier survival analyses and multivariate analysis with
      covariate adjustments. Furthermore, we knocked down TCN1 by small interfering RNA
      (siRNA) in HPSCC cell FaDu, tested the effects of TCN1 knockdown on cisplatin
      toxicity by MTT assay, and detected cisplatin-induced apoptosis by Western
      blotting. Results: TCN1 expression was significantly lower in NACT-sensitive
      patients than nonsensitive patients at protein level (p=0.013) and mRNA level
      (p<0.001), indicating that low TCN1 expression predicts better NACT treatment
      response. Furthermore, TCN1 was an independent prognostic biomarker for both
      overall survival (p=0.047) and disease-free survival (p=0.05) in advanced HPSCC
      patients. In addition, in vitro experiments showed that genetic silencing of TCN1
      using siRNA sensitized FaDu cells to cisplatin treatment with increased cell
      apoptosis. Conclusion: Low expression of TCN1 might be a novel prognostic
      biomarker for predicting NACT sensitivity and clinical outcome in local advanced
      HPSCC patients.

PMID- 30100734
TI  - Efficacy of bevacizumab versus epidermal growth factor receptor inhibitors for
      wild-type RAS metastatic colorectal cancer: a meta-analysis.
AB  - Background: Results from several prospective clinical trials comparing anti
      epidermal growth factor receptor (EGFR) therapy and anti-vascular endothelial
      growth factor (VEGF) therapy plus chemotherapy for wild-type RAS metastatic
      colorectal cancer (mCRC) have been inconsistent. This meta-analysis aims to
      investigate the optimal choice for these target agents. Methods: We searched for
      clinical trials in both electronic databases from inception until January 2018
      and recent conference abstracts to identify prospective clinical studies
      comparing the efficacy of a VEGF inhibitor (bevacizumab) versus EGFR inhibitors
      (cetuximab or panitumumab) on wild-type RAS (including its subset KRAS) mCRC. All
      analyses were conducted using RevMan 5.3 software. Results: A total of 5 studies
      were included. EGFR inhibitors were associated with a significant benefit in
      terms of overall survival (OS) compared with VEGF inhibitors in wild-type KRAS or
      wild-type RAS populations, with hazard ratios (HRs) equal to 0.86 (95% CI: 0.78,
      0.95; p=0.003) and 0.83 (95% CI: 0.72, 0.95; p=0.007), respectively. This
      survival benefit was limited to the first-line setting. No difference was found
      for progression-free survival (PFS), whereas the objective response rate (ORR)
      was significantly increased in the wild-type RAS population (OR: 0.64; 95% CI:
      0.50, 0.82; p=0.0004). No difference in OS was noted between EGFR inhibitors
      versus a VEGF inhibitor plus the FOLFIRI regimen, whereas superior survival was
      noted for EGFR inhibitors plus the mFOLFOX6 regimen versus a VEGF inhibitor (HR:
      0.75; 95% CI: 0.57, 0.98; p=0.04). PFS was significantly prolonged (HR: 1.48; 95%
      CI: 1.14, 1.92; p=0.003), whereas a trend favoring OS (HR: 1.23; 95% CI: 0.93,
      1.63; p=0.14) was noted for a VEGF inhibitor in patients with right-sided tumors,
      with no difference in the ORR (OR: 0.85; 95% CI: 0.52, 1.38; p=0.51). However,
      left-sided tumors exhibited superior OS (HR: 0.71; 95% CI: 0.59, 0.85; p=0.0002),
      PFS (HR: 0.84; 95% CI: 0.72, 0.98; p=0.03), and ORR (OR: 0.66; 95% CI: 0.48,
      0.92; p=0.01) for EGFR inhibitors. Conclusion: This meta-analysis suggests the
      superiority of anti-EGFR therapy compared with anti-VEGF therapy for mCRC with
      wild-type RAS. Primary tumor location should be taken into account in target drug
      selection. Further research is still needed to confirm which inhibitor may be a
      better choice when combined with different chemotherapy regimens.

PMID- 30100733
TI  - Effects of miRNAs on functions of breast cancer stem cells and treatment of
      breast cancer.
AB  - Breast cancer is one of the most common malignancies for women, which accounts
      for 30% of all female malignancies. The formation of breast cancer stem cells
      (BCSCs) is attributed to the acquisition of stemness of tumor cells. With self
      renewal potential, these stem cells are insensitive to either radiotherapy or
      chemotherapy but are significant in regulating tumor behaviors and drug
      resistance. MicroRNA (miRNA) is a kind of noncoding small RNA for negatively
      regulating gene expressions. Research findings suggest that many miRNAs
      specifically regulate the expression of target genes and signal pathways of
      BCSCs. They play an important role in self-renewal, growth, and metastasis of
      breast cancer cells as potential targets for treating breast cancer. These signal
      pathways include phosphatase and tensin homolog deleted on chromosome 10
      phosphatidylinositol 3-kinase/Akt, Wnt/beta-catenin, Notch, and so on. This paper
      reviews the progress of research about miRNAs in self-renewal, metastasis,
      epithelial-mesenchymal transition and metastasis, mediation of resistance to
      chemotherapies, and treatment of breast cancer.

PMID- 30100735
TI  - Analysis of change in microRNA expression profiles of lung cancer A549 cells
      treated with Radix tetrastigma hemsleyani flavonoids.
AB  - Background: The aim of this study was to determine the inhibition effects of
      Radix tetrastigma hemsleyani (RTH) flavonoids on human lung adenocarcinoma A549
      cells and the underlying molecular mechanism. RTH is an important Chinese
      traditional herb that has been widely used in cancer therapy. As an important
      type of active substance, RTH flavones (RTHF) have been shown to have good
      antiproliferative effects on various cancer cells. MicroRNAs (miRNAs) are small,
      noncoding RNA molecules that play important roles in cancer progression and
      prevention. However, the miRNA profile of RTHF-treated A549 cells has not yet
      been studied. Materials and methods: The miRNA expression profile changes of A549
      cell treated with RTHF were determined using the miRNA-seq analysis. Furthermore,
      Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment
      analyses of differentially expressed miRNAs' (DE-miRNAs) target genes were
      carried out. Results: In this study, we identified 162 miRNAs that displayed
      expression changes >1.2-fold in RTHF-treated A549 cells. GO analysis results
      showed that target genes of DE-miRNAs were significantly enriched in protein
      binding, binding, cell, cell part, intracellular, cellular process, single
      organism process, and single-organism cellular process. Pathway analysis
      illustrated that target genes of DE-miRNAs are mainly involved in endocytosis,
      axon guidance, lysosome, melanogenesis, and acute myeloid leukemia pathway.
      Conclusion: These results may assist in the better understanding of the
      anticancer effects of RTHF in A549 cells.

PMID- 30100736
TI  - Delta-tocotrienol inhibits non-small-cell lung cancer cell invasion via the
      inhibition of NF-kappaB, uPA activator, and MMP-9.
AB  - Background: Delta-tocotrienol (deltaT), an isomer of vitamin E, exhibits
      anticancer properties in different cancer types including non-small-cell lung
      cancer (NSCLC). Yet, anti-invasive effects of deltaT and its underlying cellular
      mechanism in NSCLC have not been fully explored. Matrix metalloproteinase 9 (MMP
      9)-based cell migration and invasion are critical cellular mechanisms in cancer
      development. The current evidence indicates that MMP-9 is upregulated in most
      patients, and the inhibition of MMPs is involved in decreasing invasion and
      metastasis in NSCLC. Therefore, its suppression is a promising strategy for
      attenuating cell invasion and metastasis processes in NSCLC. Purpose: The aim of
      this study was to evaluate the possibility of MMP-9 inhibition as the underlying
      mechanism behind the antimetastatic properties of deltaT on NSCLC cells. Methods:
      The effects of deltaT on cell proliferation, migration, invasion, adhesion, and
      aggregation capabilities were investigated using different cell-based assays. An
      inhibitory effect of MMP-9 enzyme activity with deltaT was also identified using
      gel zymography. Using real-time PCR and Western blot analysis, a number of
      cellular proteins, regulatory genes, and miRNA involved in the Notch-1 and
      urokinase-type plasminogen activator (uPA)-mediated MMP-9 pathways were examined.
      Results: The study found that deltaT inhibited cell proliferation, cell
      migration, invasion, aggregation, and adhesion in a concentration-dependent
      manner and reduced MMP-9 activities. Real-time PCR and Western blot analysis data
      revealed that deltaT increased miR-451 expressions and downregulated Notch-1
      mediated nuclear factor-kappaB (NF-kappaB), which led to the repressed expression
      of MMP-9 and uPA proteins. Conclusion: deltaT attenuated tumor invasion and
      metastasis by the repression of MMP-9/uPA via downregulation of Notch-1 and NF
      kappaB pathways and upregulation of miR-451. The data suggest that deltaT may
      have potential therapeutic benefit against NSCLC metastasis.

PMID- 30100737
TI  - Endoplasmic reticulum stress-mediated autophagy contributes to 5-ethylamino-9
      diethylaminobenzo[a]phenoselenazinium-mediated photodynamic therapy via the PERK
      eIF2alpha pathway.
AB  - Introduction: 5-ethylamino-9-diethylaminobenzo[a]phenoselenazinium (EtNBSe) is a
      novel synthetic bipolar photosensitizer with many promising applications. This
      study investigated the impact of EtNBSe-mediated photodynamic therapy (EtNBSe
      PDT) on the autophagy and endoplasmic reticulum (ER) stress of squamous carcinoma
      cells (A-431 cells), as well as the related molecular mechanisms. Methods: The
      potency of EtNBSe-PDT against squamous cell carcinoma was evaluated in BALB/c
      nude mice. Cell viability was evaluated using MTT. Western blotting and
      immunofluorescence were used to determine the expression levels of ER stress- and
      autophagy-related proteins. Results: Both morphological and microscopic findings
      showed that the tumor on the xenograft mice exhibited an apparent reduction in
      volume and was replaced with fibrosis 20 days after EtNBSe-PDT. Additionally, in
      an in vitro study using A-431 cells, EtNBSe-PDT was found to inhibit A-431 cell
      survival in an EtNBSe concentration- and light dose- dependent manner, and to
      induce ER stress via the PERK-eIF2alpha signaling pathway. Additionally, EtNBSe
      PDT could also induce autophagy of A-431 cells. Furthermore, the ER stress
      inhibitor 4-PBA and the eIF2alpha inhibitor salubrinal were found to inhibit the
      autophagy induced by EtNBSe-PDT. Conclusion: This study demonstrated that the
      PERK-eIF2alpha signaling pathway was involved in the ER stress induced by EtNBSe
      PDT. Meanwhile, the ER stress via the PERK-eIF2alpha pathway promoted the
      occurrence of autophagy in A-431 cells.

PMID- 30100738
TI  - Identification of prognostic risk factors for esophageal adenocarcinoma using
      bioinformatics analysis.
AB  - Purpose: Esophageal adenocarcinoma (EAC) is the most common type of esophageal
      cancer in Western countries. It is usually detected at an advanced stage and has
      a poor prognosis. The aim of this study was to identify key genes and miRNAs in
      EAC. Methods: The mRNA microarray data sets GSE1420, GSE26886, and GSE92396 and
      miRNA data set GSE16456 were downloaded from the Gene Expression Omnibus
      database. Differentially expressed genes (DEGs) and differentially expressed
      miRNAs (DEMs) were obtained using R software. Functional enrichment analysis was
      performed using the DAVID database. A protein-protein interaction (PPI) network
      and functional modules were established using the STRING database and visualized
      by Cytoscape. The targets of the DEMs were predicted using the miRecords
      database, and overlapping genes between DEGs and targets were identified. The
      prognosis-related overlapping genes were identified using Kaplan-Meier analysis
      and Cox proportional hazard analysis based on The Cancer Genome Atlas (TCGA)
      database. The differential expression of these prognosis-related genes was
      validated using the expression matrix in the TCGA database. Results: Seven
      hundred and fifteen DEGs were obtained, consisting of 313 upregulated and 402
      downregulated genes. The PPI network consisted of 281 nodes; 683 edges were
      constructed and 3 functional modules were established. Forty-four overlapping
      genes and 56 miRNA- mRNA pairs were identified. Five genes, FAM46A, RAB15,
      SLC20A1, IL1A, and ACSL1, were associated with overall survival or relapse-free
      survival. FAM46A and IL1A were found to be independent prognostic indicators for
      overall survival, and FAM46A, RAB15, and SLC20A1 were considered independent
      prognostic indicators for relapse-free survival. Among them, the overexpression
      of RAB15 and SLC20A1 and lower expression of ACSL1 were also identified in EAC
      tissues based on the expression matrix in the TCGA database. Conclusion: These
      prognosis-related genes and differentially expressed miRNA have provided
      potential biomarkers for EAC diagnosis and treatment.

PMID- 30100739
TI  - Polymorphism of IFN-gamma +874T/A associated with production of IFN-gamma affects
      human papillomavirus susceptibility in rural women from Luohe, Henan, China.
AB  - Purpose: In this paper, the association between polymorphisms of IFN-gamma
      +874T/A (rs2430561), IFN-gammaR1 -56 T/C (rs2234711), IFN-gammaR1 +95 C/T
      (rs7749390), and IFN-gammaR1 -611A/G (rs 1327474) and human papillomavirus (HPV)
      susceptibility was investigated in rural women from Luohe, Henan, China. Patients
      and methods: A total of 520 rural women were enrolled from Luohe, including 260
      with HPV infection and mild dysplasia or less and 260 without HPV infection.
      Single-nucleotide polymorphisms (SNPs) of IFN-gamma +874T/A, IFN-gammaR1 -56 T/C,
      IFN-gammaR1 +95 C/T and IFN-gammaR1 -611A/G were genotyped using TaqMan Pre
      Designed SNP Genotyping Assays. Serum IFN-gamma levels were measured using Human
      IFN-gamma Quantikine ELISA Kit. Multivariate logistic regression analysis was
      performed to identify the SNPs associated with HPV susceptibility. Serum IFN
      gamma levels were compared between different genotypes. Results: The polymorphism
      of IFN-gamma +874T/A was associated with HPV susceptibility and +874A carriers
      had an increased risk. Moreover, the odds ratio was higher in +874 AA carriers
      than in +874 AT carriers (1.672 vs 2.874). Serum IFN-gamma levels were highest in
      IFN-gamma +874 TT carriers, intermediate in AT carriers, and lowest in AA
      carriers (2.86+/-1.14 vs 1.57+/-0.79 vs 0.41+/-0.22 pg/mL, all P<0.05).
      Conclusion: The polymorphism of IFN-gamma +874T/A was associated with HPV
      susceptibility in rural women from Luohe, Henan, China, and +874A carriers had an
      increased risk. The possible mechanism was that +874A carriers had a low
      production of IFN-gamma.

PMID- 30100740
TI  - 18F-fluorodeoxyglucose positron emission tomography predicts lymph node responses
      to definitive chemoradiotherapy in esophageal squamous cell carcinoma patients.
AB  - Purpose: To evaluate the capability of 18F-fluorodeoxyglucose positron emission
      tomography/ computed tomography (18F-FDG-PET/CT) to predict the clinical response
      of metastatic lymph node (mLN) to definitive chemoradiotherapy (dCRT) and guide
      personalized radiation dose in esophageal squamous cell carcinoma (ESCC)
      patients. Patients and methods: One hundred and forty-three mLNs from 59 patients
      with ESCC treated with dCRT and who had undergone a pretreatment 18F-FDG-PET/CT
      scan were included in the study. All defined mLNs were contoured by nuclear
      medicine radiologists. Response was evaluated by contrast-enhanced computed
      tomography and 18F-FDG-PET/CT. Results: Sixty-nine mLNs showed complete response
      (CR), and 74 mLNs showed non-complete response. The 143 mLNs were divided into 4
      groups (Groups 1-4) based on the quartiles of maximum standardized uptake value
      (SUVmax-G1, SUVmax-G2, SUVmax-G3, and SUVmax-G4) and metabolic tumor volume (MTV
      G1, MTV-G2, MTV-G3, and MTV-G4). The CR rate of SUVmax-G2 was significantly
      higher than the other 3 groups. The escalated radiation dose improved the CR rate
      of lymph nodes in SUVmax-G3 (55 Gy) and SUVmax-G4 (61 Gy). The lowest CR rate was
      found in MTV-G4 (the group with the largest MTV). The escalated radiation dose
      (59.7 Gy) improved the CR rate of lymph node in MTV-Groups 3 and 4. Conclusion:
      Pretreatment metabolic parameters can predict the response of mLNs to dCRT for
      patients with ESCC. The parameters could also be used to guide personalized dose
      to mLNs.

PMID- 30100741
TI  - The role of lncRNA CASC2 on prognosis of malignant tumors: a meta-analysis and
      bioinformatics.
AB  - Background: Cancer susceptibility candidate 2 (CASC2) is characterized as a tumor
      suppressor, which was first identified to be downregulated in endometrial
      carcinoma. Accumulating evidence was provided to testify the function of CASC2 in
      malignant tumors. However, a systematic and quantitative assessment is not
      available. The present study was designed to evaluate the role of CASC2 in
      multiple carcinomas through meta-analysis and bioinformatics. Materials and
      methods: A systematic assessment of the relationship of CASC2 with tumors was
      performed by using several computerized databases from inception to December 1,
      2017. Pooled HR with 95% CI was calculated to summarize the effect. The data on
      prognosis of malignant tumors were also downloaded from The Cancer Genome Atlas
      (TCGA) project, OncoLnc, TANRIC and lncRNAtor database. Results: A total of 13
      studies with 966 cancer patients were pooled in the analysis to evaluate the
      prognostic value of CASC2 in multiple tumors and the clinical features. The
      results of the meta-analysis revealed that low expression levels of CASC2 were
      associated with poor overall survival (OS) (pooled HR=0.39, 95% CI: 0.28-0.53,
      P<0.0001). CASC2 obviously has a negative correlation with advanced tumor node
      metastasis (TNM) stage, lymph node metastasis (LNM) and T stage, respectively
      (P<0.05). There was, however, no significant difference in gender, distant
      metastasis and high differentiation (P>0.05). In the Kaplan-Meier curves with log
      rank analysis, higher expression of CASC2 was positively correlated with longer
      survival time than patients with a lower level (P<0.05), including kidney renal
      clear cell carcinoma, brain lower grade glioma, pancreatic adenocarcinoma and
      sarcoma. Conclusion: Findings from this meta-analysis suggest that lower
      expression of CASC2 is associated with poorer prognosis of cancers, as well as
      advanced TNM, LNM and T stage. Data from the bioinformatics analysis revealed
      that higher expression of CASC2 was related to longer OS in patients with
      malignant tumors.

PMID- 30100742
TI  - Elevated expression of Tiam1 is associated with poor prognosis and promotes tumor
      progression in pancreatic cancer.
AB  - Objective: T-cell lymphoma invasion and metastasis inducing factor 1 (Tiam1) is
      known to be involved in tumor progression. However, its molecular roles and
      mechanism in pancreatic ductal adenocarcinoma (PDAC) remain unclear. The purpose
      of this study is to determine Tiam1 expression levels and investigate its
      underlying molecular mechanism in PDAC. Materials and methods: Tiam1 protein
      expression levels in PDAC tissues were examined using immunohistochemistry. Tiam1
      expression was confirmed in pancreatic cancer (PC) cells by Western blot and
      immunofluorescence staining. Tiam1-silenced PC cells were created using short
      interfering RNA. Subsequently, colony formation, scratch, and migration and
      invasion assays were carried out to explore the molecular mechanisms of Tiam1 in
      PC cells. Results: The results indicated that Tiam1 expression was significantly
      higher in PDAC tissues than in paired non-tumor tissues, and overexpression of
      Tiam1 was significantly correlated with histological grade (P=0.040) and lymph
      node metastasis (P=0.031) in PDAC. The PDAC patients with high Tiam1 expression
      had significantly lower 5-year overall survival than patients with low Tiam1
      expression. More importantly, univariate and multivariate analysis suggested that
      Tiam1 expression, along with lymph node metastasis, is a significant independent
      prognostic factor for patients with PDAC. Furthermore, we also demonstrated that
      the downregulation of Tiam1 was associated with decreased cell proliferation and
      reduced migratory and invasive capability. Conclusion: High expression of Tiam1
      plays a significant role in the progression of PDAC and may be a potential
      biomarker of poor prognosis as well as a therapeutic target.

PMID- 30100743
TI  - Extracts and components of Ficus carica leaves suppress survival, cell cycle, and
      migration of triple-negative breast cancer MDA-MB-231 cells.
AB  - Background: Products from Ficus carica have been used in traditional medicine to
      treat many diseases. This study aimed to analyze anticancer effects of extracts
      of F. carica leaves on the triple-negative breast cancer cell line MDA-MB-231.
      Materials and methods: The human breast cancer cell line MDA-MB-231 was used to
      evaluate effects of F. carica extracts. Effects of F. carica on cell viability
      were evaluated using MTT assays. Cell-cycle distribution was examined using cell
      cycle analysis. Wound-healing assays were used to evaluate migration of MDA-MB
      231. Quantitative reverse-transcription polymerase chain reaction was used to
      detect levels of Bax, p53, p21, GATA3, ELF5, cyclin-dependent kinases, MMP2, and
      tissue inhibitors of metalloproteinase. Results: We investigated the mechanism of
      anti-growth effects, and found that the expressions of genes that promote
      apoptosis were increased. In addition, the treated cells illustrated increased
      portion at S phase and changed expression of cyclin-dependent kinases,
      demonstrating cell-cycle arrest at the S phase. Furthermore, treated cells showed
      decreased cell mobility, which is essential for metastasis. Two of the active
      components of F. carica leaves, bergapten and psoralen, had similar anticancer
      effects as F. carica leaf extracts, indicating that these two components might
      play important roles in anticancer effects of F. carica leaves. Conclusion: Our
      findings suggest that F. carica leaves might be a good source to develop drugs
      for suppressing cancer-cell growth and migration to treat triple-negative breast
      cancers.

PMID- 30100744
TI  - HOXA11-AS: a novel regulator in human cancer proliferation and metastasis.
AB  - Multiple studies have demonstrated that lncRNAs extensively participate in human
      cancer proliferation and metastasis. Epigenetic modification, transcriptional and
      posttranscriptional regulatory mechanisms are involved in lncRNA-led
      tumorigenesis and transfer. Recently, a novel identified homeobox (HOX) A11
      antisense lncRNA, HOXA11-AS, 1,628 bp in length, has been excessively highlighted
      to be an essential initiator and facilitator in the process of malignant tumor
      proliferation and metastasis. As found in many reports, HOXA11-AS can not only
      act as a molecular scaffold of PRC2, LSD1 and DNMT1 to epigenetically modify
      chromosomes in the nucleus but also occur as ceRNA competitively sponging miRNAs
      in the cytoplasm. Furthermore, HOXA11-AS may function as a potential biomarker
      for cancer diagnosis and prognosis. In this review, we summarize the evolvement
      and mechanisms of HOXA11-AS in proliferation and metastasis of various human
      cancers.

PMID- 30100745
TI  - Euphornin reduces proliferation of human cervical adenocarcinoma HeLa cells
      through induction of apoptosis and G2/M cell cycle arrest.
AB  - Background: The plant Euphorbia helioscopia L. has been used in traditional
      Chinese medicine for treating various disorders such as tuberculosis and edema.
      The aim of this study was to investigate the effect of euphornin, a bioactive
      compound isolated from E. helioscopia, on proliferation of human cervical
      adenocarcinoma HeLa cells by analyzing cell viability, rate of apoptosis, and
      cell cycle progression. Materials and methods: The sulforhodamine B assay was
      used to study the effect of euphornin on the proliferation of HeLa cells.
      Morphological changes to cell nuclei were identified after Hoechst 33342
      staining. Mitochondrial membrane depolarization (MMP) was analyzed after staining
      with JC-1 dye. The influence of euphornin on the apoptosis rate was analyzed by
      Annexin V/propidium iodide double staining. Fluorescence-activated cell sorting
      was applied to investigate the influence of euphornin on cell cycle progression.
      Proteins were obtained from HeLa cells and analyzed by Western blots. Results: A
      cell viability assay showed that euphornin inhibited proliferation of HeLa cells
      in a dose-dependent and time-dependent manner. Euphornin also induced apoptosis
      in a concentration-dependent manner, with the rates of apoptosis ranging from
      25.3% to 52.6%. A high concentration of euphornin was found to block HeLa cells
      at the G2/M stage. A Western blot analysis suggested that euphornin might exhibit
      antitumor activity by inducing apoptosis. Euphornin treatment altered the ratio
      of Bax/Bcl-2 in HeLa cells, which led to the release of cytochrome complex. The
      levels of cleaved caspase-3, caspase-8, caspase-9, and caspase-10 were also
      markedly increased by euphornin treatment. Analysis of cell cycles indicated that
      euphornin induced cell cycle arrest by increasing the level of the phospho-CDK1
      (Tyr15) protein. The various assays demonstrated that euphornin treatment
      resulted in a significant suppression of cell growth accompanied by G2/M cell
      cycle arrest and increased rate of apoptosis via mitochondrial and caspase
      pathways. Conclusion: Our findings suggest that euphornin has the potential to be
      used as a cancer therapeutic agent against human cervical adenocarcinoma.

PMID- 30100746
TI  - Cost-minimization analysis of degludec/liraglutide versus glargine/aspart:
      economic implications of the DUAL VII study outcomes.
AB  - Background: Diabetes represents a relevant public health problem worldwide due to
      its increasing prevalence and socioeconomic burden. There is no doubt that tight
      glycemic control reduces the development of diabetic complications such as the
      long-term costs related to the disease. The aim of our model was to calculate
      total direct costs associated with the two treatments considered in DUAL VII
      study, and hence evaluate the potential economic benefits for the National Health
      System (NHS) deriving from the use of insulin degludec plus liraglutide
      (IDegLira) in a once-daily fixed combination. Materials and methods: We applied
      the cost-minimization technique adopting the NHS point of view to the DUAL VII
      trial outcomes. In the model, developed in Microsoft Excel(r), we calculated and
      compared annual costs per patient of the two therapeutic options for type 2
      diabetes (T2D) patients not achieving glycemic control on basal insulin and
      metformin described in the trial, including costs of therapy management and side
      effects, both negative and positive. Annual treatment costs were calculated based
      on IDegLira and basal bolus end-of-trial doses resulting in a 1:2 ratio (40.4 U
      vs 84.1 U). Therefore, maintaining the IDegLira/basal bolus at 1:2 dose ratio, we
      calculated the correlation between the dose reduction and costs compared to DUAL
      VII doses base case scenario. Results: Total treatment costs were obtained by
      adding annual cost of drug, needles, glycemic self-monitoring, hypoglycemic
      events, and effect on consumption of other drugs. Total annual costs of IDegLira
      combination resulted in ?434 higher than basal bolus in DUAL VII base case (40.4
      U); the two treatments reported equal costs at 34% dose reduction (26.7 U), while
      below this value IDegLira treatment became less expensive, with about ?215 gain
      at 50% dose reduction (20.2 U). It is also important to notice that above the
      break-even point, until an IDegLira dose of 30 U, the cost difference is
      negligible in view of the clinical benefit provided by the fixed combination
      highlighted in DUAL VII trial. Conclusion: Adding the significant clinical
      findings derived from DUAL VII trial to our economic evaluation, IDegLira seems
      to offer an important alternative to basal-bolus therapy.

PMID- 30100747
TI  - The burden of cystic fibrosis in the Medicaid population.
AB  - Purpose: To conduct an analysis describing clinical characteristics, pulmonary
      exacerbation (PEx) events, and health care resource utilization among Medicaid
      insured patients with cystic fibrosis (CF). Patients and methods: A retrospective
      analysis of the Truven Health MarketScan(r) Medicaid Multi-State administrative
      claims database (2010-2014) was undertaken. Patients aged >=6 years with a CF
      diagnosis, continuously enrolled for 12 months, were identified. Demographics,
      comorbidities, PEx events, and health care resource utilization and costs over a
      12-month enrollment period were analyzed for all patients and by age groups.
      Results: In total, 1196 patients with CF aged >=6 years were identified from a
      sample size of approximately 10 million Medicaid patients. Mean (SD) age was 16.1
      (8.8) years. A greater proportion of patients were in younger age groups (6-11
      years: 35.5%, 12-17 years: 29.1%, 18-26 years: 25.6%, 27-34 years: 6.7%, >=35
      years: 3.2%). Across all age groups, approximately 90% of patients had at least 1
      PEx event; 50.7% of those had a PEx event involving treatment with intravenous
      antibiotics, and 42.8% required hospitalization. PEx recurrence was frequent:
      55.7% of all patients experienced >=3 PEx events during 1 year. Mean (SD) health
      care expenditures during a PEx event rose with increasing age, ranging from
      US$44,589 (US$139,024) to US$116,169 (US$387,752). Overall health care resource
      utilization was high among patients with CF; 47.2% of the population required an
      inpatient admission, and 26.8% had subsequent hospitalizations totaling 29.1 days
      per year in hospital. Conclusion: High rates of PEx, hospitalizations, and time
      spent in hospital demonstrate the significant health care burden of CF among
      Medicaid beneficiaries.

PMID- 30100748
TI  - Location of appendix in pregnancy: does it change?
AB  - Objectives: This study aimed to determine the change in anatomical location of
      appendix in full-term pregnancy. Study design: This was a descriptive cross
      sectional study. Place and duration of study: Liaquat National University
      Hospital, Karachi, Pakistan, Department of General Surgery, January 01 to July
      31, 2010. Patients and methods: Full-term pregnant women undergoing caesarean
      section were enrolled. The anatomical position of the appendix was noted by
      visual inspection with reference to the transtubercular plane (TTP). SPSS-10 was
      used for analysis. Results: Seventy-seven full-term pregnant female patients who
      underwent caesarean section were included in the study. Their mean age was 29
      years, the mean height was 5.3 feet, and mean gestational age was 38 weeks.
      Appendix was found at the normal anatomical location in 63 out of 77 patients
      (81.8%), while it was located above the TTP in 14 patients (18.2%). Conclusion:
      Appendix does not migrate up with increasing gestational age in the majority of
      pregnant women. In most full-term pregnant female patients, appendix is located
      at the normal anatomical position.

PMID- 30100749
TI  - Cell adhesion molecules and exercise.
AB  - Background: An extensive systematic review was undertaken in the current
      literature in order to explore the role of different types and intensities of
      exercise in cell adhesion molecules (CAMs), one of the markers of vascular
      inflammation, endothelial dysfunction, and atherosclerosis. Methods: Twenty-eight
      qualifying studies were extensively reviewed to examine the effects of different
      intensities (low-to-moderate vs. high) and types (aerobic vs. resistance) of
      exercise on intercellular adhesion molecule-1, vascular cell adhesion molecule-1,
      and selectins. Results: Low-to-moderate intensity aerobic exercise favorably
      decreased CAMs in a variety of subject populations, while CAMs momentarily
      increased immediately following high-intensity aerobic exercise, which then
      returned to the pre-exercise level within several hours post-exercise. Resistance
      exercise, regardless of its intensity, did not significantly influence CAMs.
      Conclusion: It is evident that the responses of CAMs are dependent upon the type
      and intensity of exercise performed. The most common, favorable outcome was a
      decrease in CAMs following low-to-moderate intensity aerobic exercise, while high
      intensity aerobic exercise showed a short-lived, momentary increase in CAMs,
      which returned to the pre-exercise level within a few hours post-exercise.
      Resistance exercise, regardless of its intensity, neither significantly increased
      nor decreased CAMs. Future studies should focus more on the role of exercise in
      both soluble and membrane-bound CAMs as well as proinflammatory cytokines related
      to atherosclerosis in order to develop specific exercise programing that can
      effectively improve vascular inflammation and endothelial health.

PMID- 30100750
TI  - The impact of ABCB1 (rs1045642 and rs4148738) and CES1 (rs2244613) gene
      polymorphisms on dabigatran equilibrium peak concentration in patients after
      total knee arthroplasty.
AB  - Background: Non-vitamin K oral anticoagulants (NOACs) are commonly used for
      prophylaxis of venous thromboembolism (VTE) in orthopedic patients. Despite known
      safety and high potency of NOACs, potential interactions of NOACs with genetic
      polymorphisms are poorly understood. Dabigatran etexilate is one of the most
      commonly prescribed direct thrombin inhibitors for the prevention of VTE. The
      objectives of this study were to assess the effect of ABCB1 (rs1045642 and
      rs4148738) and CES1 (rs2244613) polymorphisms on dabigatran pharmacokinetics in
      patients after total knee arthroplasty. Patients and methods: A total of 60
      patients, aged 37-81 years, who underwent surgery for knee replacement have been
      included in the study. VTE prophylaxis was conducted via administration of
      dabigatran etexilate 220 mg once daily. Genotyping for carrier state of
      polymorphic variants such as rs1045642 and rs4148738 of the ABCB1 gene and
      rs2244613 of the CES1 gene was carried out using real-time polymerase chain
      reaction (PCR). We also measured the peak and trough concentrations of plasma
      dabigatran by using high-performance liquid chromatography (HPLC). Results: Our
      study revealed that TT genotype of rs1045642 polymorphism of the ABCB1 gene was
      associated with higher dabigatran equilibrium peak concentrations and the higher
      risk of bleeding than the presence of CC genotype (p<0.008). There was no
      statistically significant genotype-dependent difference in the trough
      concentrations between rs1045642 and rs4148738 of the ABCB1 gene and rs2244613 of
      the CES1 gene. Conclusion: Our findings indicate that the polymorphisms of ABCB1
      rs1045642 may have a prominent contribution to the safety of dabigatran in
      patients after knee surgery. Moreover, TT genotype may be associated with the
      higher risk of hemorrhagic complications in this population. There were no
      influence of polymorphism of ABCB1 rs4148738 and CES1 rs2244613 on dabigatran
      peak and through concentrations. Larger studies are needed to confirm our
      observations.

PMID- 30100751
TI  - Quality of life and associated factors in Brazilian women with chronic pelvic
      pain.
AB  - Background: Chronic pelvic pain (CPP) is a common and debilitating clinical
      condition in women. Objectives: The aim of this study was to compare the quality
      of life (QoL) of women with and without CPP and to investigate factors associated
      with the QoL of women with CPP. Patients and methods: A cross-sectional study was
      conducted with 100 women with CPP and 100 women without CPP. QoL was evaluated
      using the abbreviated version of the World Health Organization QoL instrument
      (WHOQOL-BREF). Depression and anxiety were evaluated using the Hospital Anxiety
      and Depression Scale, and sexual function was evaluated using the Female Sexual
      Function Index. Generalized linear models were used to analyze the data,
      permitting comparison of QoL scores and identification of the factors affecting
      QoL. Results: Mean age (+/- SD) was 37.8+/-8.0 and 37.2+/-9.6 years for women
      with and without CPP, respectively (P=0.648). Following adjustment, women with
      CPP had significantly lower QoL scores in the physical health (P<0.001) and
      social relationships' (P=0.025) domains. Anxiety, depression, sexual dysfunction,
      hypertension, diabetes mellitus, pain intensity, lower family income, and not
      having a partner were factors negatively associated with QoL, while being
      postmenopausal, being employed, and having a child were positively associated
      with QoL in women with CPP. Conclusion: Women with CPP had poorer QoL than those
      without CPP. Factors affecting the QoL of women with CPP were identified, some
      for the first time in this population of women. Interventions targeting these
      factors may prove effective in minimizing the negative repercussion of CPP on
      QoL.

PMID- 30100752
TI  - Evaluation of combined radiofrequency and chemical blockade of multi-segmental
      lumbar sympathetic ganglia in painful diabetic peripheral neuropathy.
AB  - Background: Painful diabetic peripheral neuropathy (PDPN) is one of the most
      common complications of diabetes. PDPN seriously affects the quality of life and
      is difficult to treat; therefore, there is an urgent need for new cost-effective
      treatment methods for PDPN. Objective: To investigate the efficacy and safety of
      radiofrequency thermocoagulation (RF) combined with anhydrous ethanol (AE)
      chemical blockade of lumbar sympathetic ganglia (LSG) in patients with PDPN using
      computed tomography (CT). Study design: Retrospective comparative study. Setting:
      Shengjing Hospital of China Medical University. Methods: Ninety patients
      diagnosed with PDPN were enrolled in this study. The patients were randomly
      divided into AE group (A, n=30), RF group (B, n=30), and RF+ AE group (C, n=30).
      The follow-up included preoperative basic conditions, visual analog scale (VAS),
      the total remission rate (TRR), skin temperature (ST) and the improvement of
      numbness and hyperalgesia in the lower extremities, complications, and degree of
      satisfaction (DOS) before and after surgery. Results: Postoperative VASs were
      significantly decreased compared to preoperative VASs in all groups (P<0.05). The
      VAS in group A began to increase 3 months (3M) after surgery; VAS scores at 3M, 6
      months (6M) and 1 year (1Y) were significantly different compared to group B and
      C (P<0.05); VAS in group B began to increase after 6M; VAS scores at 6M and 1Y
      were significantly different compared to group C (P<0.05); Moreover, group C
      maintained relatively long duration of pain relief. TRR in group A, group B and
      group C at 1Y after operation was 66.7%, 73.3% and 93.3%, respectively; TRR in
      group C was statistically different compared to groups A and B (P<0.05). Higher
      ST in the lower extremities was observed after surgery in all groups compared to
      peroration (P<0.05); nonetheless, the difference was not statistically
      significant. The numbness and hyperalgesia improved in all three groups after
      surgery compared to preoperational time, the numbness in group C was
      significantly higher compared to groups A and B. In addition, no severe
      complications were observed. At 6M and 1Y after surgery, the degree of
      satisfaction in patients from group C was significantly higher compared to groups
      A and B. Conclusion: Radiofrequency thermocoagulation combined with AE chemical
      blockade of the LSG was safe and effective. Nevertheless, the details underlying
      analgesic mechanisms still need to be investigated.

PMID- 30100753
TI  - Evaluating comfort measures for commonly performed painful procedures in
      pediatric patients.
AB  - Introduction: Management of pediatric pain from medical procedures is of great
      importance for improving both patient care and experience. In this study, we
      investigated methods of managing acute pain in infants and children by studying
      the correlation between the number of attempts to complete painful procedures,
      given different comfort measures. Methods: The study is a retrospective review of
      74,276 procedures performed at two pediatric hospitals in an integrated academic
      children's health system between 2013 and 2016. We compared three comfort
      measures most frequently offered: positions of comfort (POC), distraction (DIST),
      and pharmacological (PHARM). These methods were compared in the setting of four
      procedures: peripheral intravenous (PIV) catheter insertion, gastrointestinal
      tube placement, incision procedures, and bladder catheterization. We used the
      number of attempts needed to complete a procedure as a measure of efficacy
      minimizing distressing experience in an acutely painful setting (single attempt
      vs repeat attempts). Results: Among younger children, DIST appears superior to
      the other two methods; it performs significantly better for three of the four
      procedures (PIV catheterization, incision wound, and urinary catheterization)
      among infants aged <1 year and for PIV catheterization among toddlers aged 1-3
      years. For older children, POC tends to perform slightly better than the other
      two methods, although it is significantly better only for PIV catheterization
      among adolescents aged 13-21 years and urinary catheterization among children
      aged 9-12 years. Conclusion: Results from this study may be used to determine
      appropriate comfort measures for painful procedures in pediatric setting.

PMID- 30100754
TI  - Prognostic value of subcutaneous adipose tissue volume in hepatocellular
      carcinoma treated with transcatheter intra-arterial therapy.
AB  - Background: Prognosis of patients with hepatocellular carcinoma (HCC) who undergo
      transcatheter intra-arterial therapies, including transcatheter arterial
      chemoembolization and transcatheter arterial infusion chemotherapy, is affected
      by many clinical factors including liver function and tumor progression. However,
      the effect of body composition such as skeletal muscle and visceral and
      subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of
      these patients remains unclear. We investigated the prognostic value of body
      composition in HCC patients treated with transcatheter intra-arterial therapies.
      Patients and methods: This study retrospectively evaluated 100 HCC patients
      treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas
      of skeletal muscle, VAT, and SAT were measured on computed tomography images at
      third lumbar vertebra level and normalized by the height squared to calculate the
      skeletal muscle index, VAT index, and SAT index (SATI). The visceral to
      subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS)
      was compared between high- and low-index groups for each body composition.
      Furthermore, prognostic significance was assessed by univariate and multivariate
      analyses using Cox proportional hazards models. Results: Among the body
      composition indexes, only SATI could significantly differentiate OS (p=0.012).
      Multivariate analysis showed that SATI (low- vs. high-SATI: HR, 2.065; 95% CI,
      1.187-3.593; p=0.010), serum albumin (<3.5 vs. >=3.5 g/dL; HR, 2.007; 95% CI,
      1.037-3.886; p=0.039), serum alpha-fetoprotein (<20 vs. >=20 ng/mL; HR, 0.311;
      95% CI, 0.179-0.540; p<0.001), and Modified Response Evaluation Criteria in Solid
      Tumors assessment (complete response+partial response+stable disease vs.
      progressive disease; HR, 0.392; 95% CI, 0.221-0.696; p=0.001) were indicated as
      independent prognostic factors for OS. Conclusion: High SAT volume is associated
      with better survival outcomes in HCC patients treated with transcatheter intra
      arterial therapies. Elucidation of the mechanisms regulating SAT volume may offer
      a new therapeutic strategy for these patients.

PMID- 30100755
TI  - PRAF2 expression indicates unfavorable clinical outcome in hepatocellular
      carcinoma.
AB  - Introduction: Prenylated Rab acceptor 1 domain family member 2 (PRAF2), a novel
      oncogene, has been shown to be essential for the development of several human
      cancers; however, its role in hepatocellular carcinoma (HCC) remains unclear.
      Materials and methods: PRAF2 mRNA and protein expressions were examined in fresh
      tissues by quantitative reverse transcription-polymerase chain reaction and
      Western blot, respectively, and in 518 paraffin-embedded HCC samples by
      immunohistochemistry. The correlation of PRAF2 expression and clinical outcomes
      was determined by the Student's t-test, Kaplan-Meier test, and multivariate Cox
      regression analysis. The role of PRAF2 in HCC was investigated by cell viability,
      colony formation, and migration assays in vitro and with a nude mouse model in
      vivo. Results: In our study, the PRAF2 expression was noticeably increased in HCC
      tissues at both the mRNA and protein levels compared with that of the nontumorous
      tissues. Kaplan-Meier analysis indicated that high PRAF2 expression was
      correlated with worse overall survival in a cohort of 518 patients with HCC. The
      prognostic implication of PRAF2 was verified by stratified survival analysis. The
      multivariate Cox regression model revealed PRAF2 as an independent poor
      prognostic factor for overall survival (hazard ratio = 1.244, 95% CI: 1.039
      1.498, P<0.017) in HCC. The in vitro data demonstrated that PRAF2 overexpression
      markedly enhanced cell viability, colony formation, and cell migration. Moreover,
      ectopic expression of PRAF2 promoted tumor growth and metastasis in vivo.
      Conclusion: Collectively, we conclude that PRAF2 is increased in HCC and is a
      novel unfavorable biomarker for prognostic prediction for patients with HCC.

PMID- 30100756
TI  - MicroRNAs, long noncoding RNAs, and circular RNAs: potential tumor biomarkers and
      targets for colorectal cancer.
AB  - Noncoding RNAs (ncRNAs) can be divided into microRNAs (miRNAs), long noncoding
      RNAs (lncRNAs), circular RNAs (circRNAs), pRNAs, and tRNAs. Traditionally, miRNAs
      exert their biological function mainly through the inhibition of translation via
      the induction of target RNA transcript degradation. lncRNAs and circRNAs were
      once considered to have no potential to code proteins. Here, we will review the
      current knowledge on ncRNAs in relation to their origins, characteristics, and
      functions. We will also review how ncRNAs work as competitive endogenous RNA,
      gene transcription and expression regulators, and RNA-binding protein sponges in
      colorectal cancer (CRC). Notably, except for the abovementioned mechanisms,
      recent advances revealed that lncRNAs can also act as the precursor of miRNAs,
      and a small portion of lncRNAs and circRNAs was verified to have the potential to
      code proteins, providing new evidence for the significance of ncRNAs in CRC
      tumorigenesis and development.

PMID- 30100757
TI  - Disparities of age-based cancer-specific survival improvement with various
      clinicopathologic characteristics for kidney cancer.
AB  - Introduction: Whether or not age is a predictor of kidney cancer survival is
      currently unknown but debated. It is also unknown whether improved kidney cancer
      survival is associated with age with particular clinicopathologic
      characteristics. The aim of this study was to evaluate kidney cancer survival in
      four age-based subgroups of patients by analyzing the Surveillance, Epidemiology,
      and End Results-registered database. Methods: Age-based survival disparity by
      sex, race, marital status, year of diagnosis, pathological grade, histological
      type, and stage was measured. The impact of age and further parameters on disease
      specific mortality was evaluated by multivariate Cox proportional hazards
      regression analyses. Results: Results showed that 8-year cancer-specific survival
      was 79.6% in those aged <=49 years, 70.6% in those aged 50-64 years, 65.3% in
      those aged 65-74 years, and 56.0% in those aged 75-84 years. These differences
      were significant as judged by a univariate log-rank test (P<0.001) and
      multivariate Cox regression (P<0.001). Age-based survival improvement was most
      obvious in patients diagnosed from 2005 to 2009 and with the following
      clinicopathologic characteristics: female, white race, low pathological grade,
      and localized stage. There was no obvious disparity of age-based survival
      improvement with regard to marital status or histologic type. No age-based
      survival improvement was observed in patients of the black race, pathological
      grade IV, or distant stage (P=0.05, P=0.07, and P=0.07, respectively).
      Conclusion: These data suggest that age is an independent prognostic factor for
      survival in patients with kidney cancer and that age-based survival improvement
      is associated with particular clinicopathologic characteristics.

PMID- 30100758
TI  - FAM98A promotes proliferation of non-small cell lung cancer cells via the P38
      ATF2 signaling pathway.
AB  - Background: FAM98A, a novel protein, is expressed in ovarian and colorectal
      cancer tissues. However, the association between FAM98A expression and the
      clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains
      undetermined. Materials and methods: The FAM98A expression pattern was determined
      in NSCLC samples and corresponding adjacent normal lung tissues using
      immunohistochemical staining and Western blotting. The association of FAM98A
      expression with clinicopathological characteristics was measured in 131 NSCLC
      samples. Finally, the overexpression and inhibition of FAM98A was performed in
      the A549 and SPC-A1 cell lines to explore its role in the development of lung
      cancer. Results: Western blot analysis of 20 paired NSCLC samples showed that
      expression of FAM98A was higher in lung cancer tissues than in the corresponding
      adjacent normal lung tissues (p<0.05). Immunohistochemical staining of 128 NSCLC
      specimens showed that expression of FAM98A was significantly higher in lung
      cancer samples than in adjacent normal lung tissues (118/128 vs 10/128; p<0.001).
      Positive expression of FAM98A was significantly related to tumor TNM stage
      (p<0.05) and lymph node metastasis (p<0.001). Additionally, overexpression of
      FAM98A induced an increase in the expression of phosphorylated P38,
      phosphorylated ATF2, and cyclin D1, which promoted proliferation of lung cancer
      cells. Correspondingly, the effects of FAM98A overexpression were reversed by
      administration of a specific inhibitor of phosphorylated P38. Conclusion: FAM98A
      was overexpressed in the cytoplasm of NSCLC samples and correlated with advanced
      TNM staging and lymph node metastasis. Thus, FAM98A increases the expression of
      cyclin D1 by activating the P38-ATF2 signaling pathway and subsequently enhancing
      tumor cell proliferation; these results are promising and need further
      validation.

PMID- 30100759
TI  - Association of obesity, diabetes and hypertension with cognitive impairment in
      older age.
AB  - Background: Age-related cognitive impairment is rising in prevalence but is not
      yet fully characterized in terms of its epidemiology. Here, we aimed to elucidate
      the role of obesity, diabetes and hypertension as candidate risk factors.
      Methods: Original baseline data from 3 studies (OCTOPUS, DECS, SuDoCo) were
      obtained for secondary analysis of cross-sectional associations of diabetes,
      hypertension, blood pressure, obesity (body mass index [BMI] >=30 kg/m2) and BMI
      with presence of cognitive impairment in log-binomial regression analyses.
      Cognitive impairment was defined as scoring more than 2 standard deviations below
      controls on at least one of 5-11 cognitive tests. Underweight participants
      (BMI<18.5 kg/m2) were excluded. Results were pooled across studies in fixed
      effects inverse variance models. Results: Analyses totaled 1545 participants with
      a mean age of 61 years (OCTOPUS) to 70 years (SuDoCo). Cognitive impairment was
      found in 29.0% of participants in DECS, 8.2% in SuDoCo and 45.6% in OCTOPUS. In
      pooled analyses, after adjustment for age, sex, diabetes and hypertension,
      obesity was associated with a 1.29-fold increased prevalence of cognitive
      impairment (risk ratio [RR] 1.29; 95% CI 0.98, 1.72). Each 1 kg/m2 increment in
      BMI was associated with 3% increased prevalence (RR 1.03; 95% CI 1.00, 1.06).
      None of the remaining risk factors were associated with impairment. Conclusion:
      Our results show that older people who are obese have higher prevalence of
      cognitive impairment compared with normal weight and overweight individuals, and
      independently of co-morbid hypertension or diabetes. Prospective studies are
      needed to investigate the temporal relationship of the association.

PMID- 30100760
TI  - Cross-national health care database utilization between Spain and France: results
      from the EPICHRONIC study assessing the prevalence of type 2 diabetes mellitus.
AB  - Aim: The EPICHRONIC (EPIdemiology of CHRONIC diseases) project investigated the
      possibility of developing common procedures for French and Spanish electronic
      health care databases to enable large-scale pharmacoepidemiological studies on
      chronic diseases. A feasibility study assessed the prevalence of type 2 diabetes
      mellitus (T2DM) in Navarre and the Basque Country (Spain) and the Midi-Pyrenees
      region (France). Patients and methods: We described and compared database
      structures and the availability of hospital, outpatient, and drug-dispensing data
      from 5.9 million inhabitants. Due to differences in database structures and
      recorded data, we could not develop a common procedure to estimate T2DM
      prevalence, but identified an algorithm specific to each database. Patients were
      identified using primary care diagnosis codes previously validated in Spanish
      databases and a combination of primary care diagnosis codes, hospital diagnosis
      codes, and data on exposure to oral antidiabetic drugs from the French database.
      Results: Spanish and French databases (the latter termed Systeme National
      d'Information Inter-Regimes de l'Assurance Maladie [SNIIRAM]) included
      demographic, primary care diagnoses, hospital diagnoses, and outpatient drug
      dispensing data. Diagnoses were encoded using the International Classification of
      Primary Care (version 2) and the International Classification of Diseases,
      version 9 and version 10 (ICD-9 and ICD-10) in the Spanish databases, whereas the
      SNIIRAM contained ICD-10 codes. All data were anonymized before transferring to
      researchers. T2DM prevalence in the population over 20 years was estimated to be
      6.6-7.0% in the Spanish regions and 6.3% in the Midi-Pyrenees region with ~2%
      higher estimates for males in the three regions. Conclusion: Tailored procedures
      can be designed to estimate the prevalence of T2DM in population-based studies
      from Spanish and French electronic health care records.

PMID- 30100761
TI  - Applying a common data model to Asian databases for multinational
      pharmacoepidemiologic studies: opportunities and challenges.
AB  - Objective: The goal of the Asian Pharmacoepidemiology Network is to study the
      effectiveness and safety of medications commonly used in Asia using databases
      from individual Asian countries. An efficient infrastructure to support
      multinational pharmacoepidemiologic studies is critical to this effort. Study
      design and setting: We converted data from the Japan Medical Data Center
      database, Taiwan's National Health Insurance Research Database, Hong Kong's
      Clinical Data Analysis and Reporting System, South Korea's Ajou University School
      of Medicine database, and the US Medicare 5% sample to the Observational Medical
      Outcome Partnership common data model (CDM). Results: We completed and documented
      the process for the CDM conversion. The coordinating center and participating
      sites reviewed the documents and refined the conversions based on the comments.
      The time required to convert data to the CDM varied widely across sites and
      included conversion to standard terminology codes and refinements of the
      conversion based on reviews. We mapped 97.2%, 86.7%, 92.6%, and 80.1% of domestic
      drug codes from the USA, Taiwan, Hong Kong, and Korea to RxNorm, respectively.
      The mapping rate from Japanese domestic drug codes to RxNorm (70.7%) was lower
      than from other countries, and we mapped remaining unmapped drugs to Anatomical
      Therapeutic Chemical Classification System codes. Because the native databases
      used international procedure coding systems for which mapping tables have been
      established, we were able to map >90% of diagnosis and procedure codes to
      standard terminology codes. Conclusion: The CDM established the foundation and
      reinforced collaboration for multinational pharmacoepidemiologic studies in Asia.
      Mapping of terminology codes was the greatest challenge, because of differences
      in health systems, cultures, and coding systems.

PMID- 30100762
TI  - Ex vivo decontamination of yeast-colonized dentures by iodine-thiocyanate
      complexes.
AB  - Introduction: Under well-defined experimental conditions, and in the presence of
      hydrogen peroxide, lactoperoxidase produces stable iodine-thiocyanate complexes
      that have antimicrobial properties. A novel process was developed to short
      circuit the consumption of hydrogen peroxide by microbial catalases by producing
      iodine-thiocyanate complexes prior to contact with microorganisms, with the aim
      of being able to decontaminate the ex vivo dentures colonized by yeasts.
      Materials and methods: Teabags containing lactoperoxidase adsorbed on inert clay
      beads were immersed for 1 minute in phosphate buffer solution (0.1 M pH 7.4)
      containing 5.2 mM potassium iodide, 1.2 mM potassium thiocyanate, and 5.5 mM
      hydrogen peroxide. After removing the adsorbed lactoperoxidase, the stability and
      efficacy of iodine-thiocyanate complexes for Candida-colonized denture
      decontamination were verified. Investigations were performed in vitro on Candida
      albicans ATCC 10231 and on clinical isolates from 46 dentures. A Candida plate
      count was performed after a 24-hour incubation at 37 degrees C on Sabouraud
      chloramphenicol or CHROMagar solid media; then, the yeast growth was evaluated in
      Sabouraud broth by turbidimetry and biofilm biomass by crystal violet staining.
      Results: In vitro tests demonstrated the effectiveness of the oxidant solution in
      sterilizing a suspension of 106Candida cells per milliliter after a 5-minute
      incubation. A single ex vivo immersion of contaminated dentures in a solution of
      iodine-thiocyanate complexes led to a decrease of at least 1 log unit in the
      number of colony-forming units in 58.3% of the tested dentures, while immersing
      in water alone had no effect on denture colonization (significant c2: p =
      0.0006). Conclusion: These data suggest a promising new strategy for
      decontamination of dentures.

PMID- 30100763
TI  - Hospital emergency department visits by ambulance for nontraumatic tooth pain in
      the USA.
AB  - Objective: This study examined the prevalence of ambulance use for nontraumatic
      tooth pain (NTP) visit to emergency departments (EDs) and the factors associated
      with ambulance use for NTP in the USA. Materials and methods: Data from the
      National Hospital Ambulatory Medical Care survey conducted in the USA from 2003
      to 2012 were analyzed. Descriptive statistics were obtained, and multivariable
      logistic regression was used to determine associations with ambulance use for
      NTP. Results: The total proportion of ED visits due to NTP by ambulance was 1.1%,
      lowest in 2008 (0.43%) and highest in 2011 (2.28%). The proportion of ED visits
      due to NTP by ambulance was highest among public insurance enrollees (1.9%),
      Hispanics (2.3%) and those aged 45-64 years (2.7%). In the multivariable
      analysis, those aged 45-64 years had approximately four times higher odds of an
      ED visit for NTP by ambulance compared to those aged 25-44 years. Conclusion:
      This study demonstrates that transport to EDs by ambulance for NTP does occur at
      a measurable rate and adults aged 45-64 years had significantly higher odds of ED
      visits for NTP by ambulance.

PMID- 30100764
TI  - Removal of silicone oil droplets adhering to the posterior surface of an
      intraocular lens (IOL).
AB  - Purpose: We report a rare case of silicone oil droplets adhering to the posterior
      surface of an intraocular lens (IOL) after removal of silicone oil for a patient
      with retinal reattachment, who had a history of pseudophakic rhegmatogenous
      retinal detachment. Case report: A 45-year-old male with a history of cataract
      surgeries of both eyes developed pseudophakic retinal detachment in his left eye.
      He received surgeries of scleral buckle and standard 3-port pars plana vitrectomy
      with silicon oil tamponade. With retinal attachment for 7 months, he underwent
      removal of silicone oil in the left eye. However, a big silicone oil droplet was
      found on the posterior surface of the IOL with complaints of distorted micropsia
      and poor vision, a month later. Pars plana vitrectomy using a 20-gauge vitreous
      cutter, which was supposed to have a higher cleaning capability compared with a
      smaller size device, was performed to aspirate the main part of the big oil
      droplet. The residual dispersed smaller droplets at the center of the visual axis
      were swept peripherally using a 27-gauge bending tip cannula. Fortunately, the
      patient regained his vision of 20/20 without distortion and micropsia in his left
      eye. Conclusion: This was a rare case where silicone oil droplets were found
      adhering to the posterior surface of an IOL after removing silicone oil a month
      later. We used a 20-gauge vitrectomy system to remove large oil droplets and
      swept smaller ones off the visual axis to improve the vision and visual quality.

PMID- 30100765
TI  - Surgical management of a conjunctival nevus with amniotic membrane
      transplantation.
AB  - Purpose: Nevi of the conjunctiva are usually benign pigmented tumorous lesions
      located in the bulbar conjunctiva. In most conjunctival nevus cases, the patient
      wants the lesion to be removed for cosmetic reasons, but excisional biopsies are
      best for lesions suspicious for malignancy. This case report illustrates the
      intraoperative surgical management, histological findings, and the course of
      healing in a conjunctival nevus patient. Case report: A 26-year-old man was
      referred to our eye hospital with a large bulbar conjunctival nevus of the right
      eye. Upon examination, there was a large pigmented lesion with numerous small
      cysts present on the superior bulbar conjunctiva. The conjunctival tumor was
      resected, and an amniotic membrane transplantation was performed for the bulbar
      conjunctival reconstruction. The histopathological diagnosis suggested a
      conjunctival nevus. After the resection, a reduction in the inflammation and
      healing of the conjunctival lesion could be seen. The epithelialization of the
      bulbar conjunctiva over the amniotic membrane was complete 4 weeks after the
      resection. At the 6-month follow-up, there was no sign of recurrence or any
      postoperative complications. Conclusion: A surgical excision combined with
      reconstruction via amniotic membrane transplantation is effective and economical
      for the treatment of large conjunctival lesions.

PMID- 30100767
TI  - Development and usability of a new subcutaneous auto-injector device to
      administer hydroxyprogesterone caproate to reduce the risk of recurrent preterm
      birth.
AB  - Background: Current administration of hydroxyprogesterone caproate (HPC) by
      intramuscular injection is associated with limitations, including the potential
      for human error and contamination, patient anxiety, and increased risk of
      needlestick injury. Objective: To describe the design of an auto-injector for
      subcutaneous (SC) administration of HPC and the results of studies that evaluated
      the target user's understanding of the proper use of this device. Materials and
      methods: A single-use, prefilled, fixed-dose, disposable auto-injector intended
      for the SC administration of HPC was developed, and its usability by health care
      providers was evaluated in 3 formative (N=32, 64 injections) and 3 validation
      studies (N=45, 90 injections). These studies consisted of one-on-one testing
      sessions performed in a simulated home environment. Analyses were based on
      observed use error or use difficulty during the performance of specific tasks,
      including those considered critical (associated with high severity harms).
      Results: In the formative studies, the majority of participants correctly
      administered an injection with the auto-injector, but prior training improved
      performance. Specific errors were noted, including holding the device at the
      injection site for a period inconsistent with its instructions for use (IFU). The
      IFU was modified to reduce potential occurrence of these errors. Use errors were
      subsequently observed on critical tasks in the first and second validation
      studies, including hold-time errors that were attributed to using visual cues
      rather than counting seconds. For the third validation study, the IFU was
      modified to focus on visual cues and all users were able to successfully perform
      the injection per the IFU. Conclusion: An auto-injector device for SC
      administration of HPC for reduction in risk of recurrent preterm birth was
      successfully developed through iterative design and validation testing. The
      device design provides high usability and acceptance of this device by health
      care professionals.

PMID- 30100768
TI  - Changes in cerebral oxygenation based on intraoperative ventilation strategy.
AB  - Introduction: Cerebral oxygenation can be monitored clinically by cerebral
      oximetry (regional oxygen saturation, rSO2) using near-infrared spectroscopy
      (NIRS). Changes in rSO2 have been shown to precede changes in pulse oximetry,
      providing an early detection of clinical deterioration. Cerebral oximetry values
      may be affected by various factors, including changes in ventilation. The aim of
      this study was to evaluate the changes in rSO2 during intraoperative changes in
      mechanical ventilation. Patients and methods: Following the approval of the
      institutional review board (IRB), tissue and cerebral oxygenation were monitored
      intraoperatively using NIRS. Prior to anesthetic induction, the NIRS monitor was
      placed on the forehead and over the deltoid muscle to obtain baseline values.
      NIRS measurements were recorded each minute over a 5-min period during general
      anesthesia at four phases of ventilation: 1) normocarbia (35-40 mmHg) with a low
      fraction of inspired oxygen (FiO2) of 0.3; 2) hypocarbia (25-30 mmHg) and low
      FiO2 of 0.3; 3) hypocarbia and a high FiO2 of 0.6; and 4) normocarbia and a high
      FiO2. NIRS measurements during each phase were compared with sequential phases
      using paired t-tests. Results: The study cohort included 30 adolescents. Baseline
      cerebral and tissue oxygenation were 81% +/- 9% and 87% +/- 5%, respectively.
      During phase 1, cerebral rSO2 was 83% +/- 8%, which decreased to 79% +/- 8% in
      phase 2 (hypocarbia and low FiO2). Cerebral oxygenation partially recovered
      during phase 3 (81% +/- 9%) with the increase in FiO2 and then returned to
      baseline during phase 4 (83% +/- 8%). Each sequential change (e.g., phase 1 to
      phase 2) in cerebral oxygenation was statistically significant (p < 0.01). Tissue
      oxygenation remained at 87%-88% throughout the study. Conclusion: Cerebral
      oxygenation declined slightly during general anesthesia with the transition from
      normocarbia to hypocarbic conditions. The rSO2 decrease related to hypocarbia was
      easily reversed with a return to baseline values by the administration of
      supplemental oxygen (60% vs. 30%).

PMID- 30100766
TI  - Polyethylene glycol in spinal cord injury repair: a critical review.
AB  - Polyethylene glycol (PEG) is a synthetic biocompatible polymer with many useful
      properties for developing therapeutics to treat spinal cord injury. Direct
      application of PEG as a fusogen to the injury site can repair cell membranes,
      mitigate oxidative stress, and promote axonal regeneration to restore motor
      function. PEG can be covalently or noncovalently conjugated to proteins,
      peptides, and nanoparticles to limit their clearance by the reticuloendothelial
      system, reduce their immunogenicity, and facilitate crossing the blood-brain
      barrier. Cross-linking PEG produces hydrogels that can act as delivery vehicles
      for bioactive molecules including growth factors and cells such as bone marrow
      stromal cells, which can modulate the inflammatory response and support neural
      tissue regeneration. PEG hydrogels can be cross-linked in vitro or delivered as
      an injectable formulation that can gel in situ at the site of injury. Chemical
      and mechanical properties of PEG hydrogels are tunable and must be optimized for
      creating the most favorable delivery environment. Peptides mimicking
      extracellular matrix protein such as laminin and n-cadherin can be incorporated
      into PEG hydrogels to promote neural differentiation and axonal extensions.
      Different hydrogel cross-linking densities and stiffness will also affect the
      differentiation process. PEG hydrogels with a gradient of peptide concentrations
      or Young's modulus have been developed to systematically study these factors.
      This review will describe these and other recent advancements of PEG in the field
      of spinal cord injury in greater detail.

PMID- 30100769
TI  - Epidemiology, prognostic factors, and outcome of trauma patients admitted in a
      Brazilian intensive care unit.
AB  - Background: Trauma is a major cause of hospital admissions and is associated with
      manifold complications and high mortality rates. However, data on intensive care
      unit (ICU) admissions are scarce in developing and low-income countries, where
      its incidence has been increasing. Objectives: To analyze epidemiological and
      clinical factors and outcomes in adult trauma patients admitted to the ICU of a
      public teaching hospital in a developing country as well as to identify risk
      factors for complications in the ICU. Patients and methods: Retrospective cohort
      of adult trauma patients admitted to the general ICU of a public teaching
      hospital in southern Brazil in the year 2012. Demographic, clinical, and outcome
      data from the ICU were analyzed. Results: During the study period, 144 trauma
      patients were admitted (83% male, Acute Physiology and Chronic Health Evaluation
      Score II =18.6+/-7.2, age =33.3 years, 93% required mechanical ventilation). Of
      these, 60.4% suffered a traffic accident (52% motorcycle), and 31.2% were victims
      of violence (aggressions, gunshot wounds, or stabbing); 71% had brain trauma, 37%
      had chest trauma, and 21% had abdominal trauma. Patients with trauma presented a
      high incidence of complications, such as infections, acute renal failure, acute
      respiratory distress syndrome, and thrombocytopenia. The ICU mortality rate was
      22.9%. Conclusion: In a Brazilian public teaching ICU, there was a great
      variability of trauma etiologies (mainly traffic accidents with motorcycles and
      victims of violence); patients with trauma had a high incidence of complications
      and mortality in the ICU.

PMID- 30100770
TI  - Swimming-induced pulmonary edema: current perspectives.
AB  - With the growing popularity of water-based sports, cases of swimming-induced
      pulmonary edema (SIPE) are becoming increasingly recognized. SIPE, a potentially
      life-threatening condition, is an acute cause of breathlessness in athletes. It
      has been described frequently in scuba divers, swimmers, and triathletes and is
      characterized by symptoms and signs of pulmonary edema following water immersion.
      It is important to recognize that athletes' symptoms can present with a spectrum
      of severity from mild breathlessness to severe dyspnea, hemoptysis, and hypoxia.
      In most cases, there is rapid resolution of symptoms within 48 hours of exiting
      the water. Recent advances in the understanding of the pathophysiology of SIPE,
      particularly regarding exaggerated pulmonary vascular pressures, have begun to
      explain this elusive condition more clearly and to distinguish its predisposing
      factors. It is essential that event organizers and athletes are aware of SIPE.
      Prompt recognition is required not only to prevent drowning, but also to
      implement appropriate medical management and subsequent advice regarding return
      to swimming and the risk of recurrence. This manuscript provides a current
      perspective on SIPE regarding the incidence rate, the current understanding of
      the pathophysiology, clinical presentation, medical management, recurrence rates,
      and advice on return to sport.

PMID- 30100771
TI  - Affective commitment foci as parallel mediators of the relationship between
      workplace romance and employee job performance: a cross-cultural comparison of
      the People's Republic of China and Pakistan.
AB  - Purpose: The purpose of the present study is twofold. First, we examined the
      relationship between workplace romance and employee job performance and tested
      the role of affective commitment foci - namely, affective coworker commitment,
      affective supervisor commitment, and affective organizational commitment - as
      parallel mediators in the relationship between workplace romance and employee job
      performance. Second, we tested the moderating role of culture on the
      interrelationships between workplace romance, affective commitment foci, and
      employee job performance. Methods: A two-wave (3-month interval) survey data were
      collected from 312 paramedics - 162 and 150 from Pakistani and Chinese public
      sector hospitals, respectively. The first and second waves of data collection
      took place in January and May 2017, respectively. Structural equation modeling
      (SEM), bootstrapping technique, and multigroup analysis were used to test the
      interrelationships between workplace romance, affective commitment foci, and
      employee job performance and to examine the cross-cultural differences in these
      interrelations. Results: Results obtained using SEM show that workplace romance
      positively influences employee performance. Importantly, the study revealed that
      the three foci of affective commitment - namely, coworker affective commitment,
      supervisor affective commitment, and organizational affective commitment - as
      parallel mediators fully mediate the relationship between workplace romance and
      employee performance. Moreover, national culture moderates the indirect
      relationship between workplace romance and employee job performance, where
      workplace romance is stronger for the Chinese data sample. Conclusion: It is
      concluded that workplace romance is positively related to employee job
      performance and that affective commitment foci fully mediate the positive
      relationship between workplace romance and employee job performance. Moreover,
      culture moderates the indirect relationship between workplace romance and
      employee job performance. The study contributes to theory and practice by
      studying an essential but largely ignored aspect of the workplace and portraying
      it as a constructive influence on employee job performance and their affective
      commitment to coworkers, supervisor, and organization.

PMID- 30100772
TI  - Administering the Routine Activities domain of the Oxford Participation and
      Activities Questionnaire as a stand-alone scale: the Oxford Routine Activities
      Measure.
AB  - Background: The recently validated Oxford Participation and Activities
      Questionnaire (Ox-PAQ) is a 23-item patient-reported outcome measure,
      theoretically grounded in the World Health Organization International
      Classification of Functioning, Disability and Health. The measure is specifically
      designed to assess participation and activity in people experiencing a range of
      health conditions. Initial validation of the Ox-PAQ identified three domains:
      Routine Activities (14 items), Emotional Well-Being (5 items), and Social
      Engagement (4 items). The purpose of the analysis reported here was to assess
      whether the Routine Activities domain of Ox-PAQ could be validated for use as a
      stand-alone measure without compromising its psychometric integrity. Methods:
      Three hundred and seventy-three patients with a diagnosis of either chronic
      obstructive pulmonary disease, multiple sclerosis, or Parkinson's disease were
      administered the Ox-PAQ in an online survey. The 14 items of the Routine
      Activities domain of the Ox-PAQ were subject to factor analytic techniques and
      assessed for reliability and validity. Results: Three hundred and forty-one
      patients fully completed the survey, a completion rate of 91.4%. The 14 items
      loaded onto one single factor with an eigenvalue of 9.29 explaining 66.35% of
      variance. Reliability was confirmed through corrected item-total correlations
      ranging from 0.880 to 0.594 and a Cronbach's alpha value of 0.96. Validity was
      demonstrated through significant differences in scores between the three disease
      groups assessed. Conclusion: Results indicate that the Ox-PAQ Routine Activities
      domain can be legitimately adopted as a stand-alone measure, the Oxford Routine
      Activities Measure, where researchers wish to focus primarily on the activity
      component of the Ox-PAQ. It should, however, be emphasized that where a full
      assessment of all areas of activity and participation highlighted as important
      during the development of the Ox-PAQ is required, all three domains of the full
      measure should be administered.

PMID- 30100773
TI  - Patient-reported outcomes in head and neck cancer: prospective multi
      institutional patient-reported toxicity.
AB  - Purpose: Head and neck cancer is occurring in an increasingly younger patient
      population, with treatment toxicity that can cause significant morbidity. Using a
      patient guided, Internet-based survivorship care plan program, we obtained and
      looked at patterns of patient-reported outcomes data from survivors seeking
      information after treatment for head and neck cancer. Methods: The Internet-based
      OncoLife and LIVESTRONG Care Plan programs were employed, which design unique
      survivorship care plans based on patient-reported data. Care plans created for
      survivors of head and neck cancer were used in this evaluation. Demographics,
      treatment modality, and toxicity were included in this evaluation. Toxicity was
      further analyzed, grouped into system-based subsets. Results: A total of 602 care
      plans were created from self-identified head and neck cancer survivors, from
      which patient-reported outcome data were attained. A majority of patients were
      Caucasian (96.2%) with median age at diagnosis of 55 years, living in suburban
      locations (39.9%), with ~50% receiving care within 20 miles of their residence.
      There was an equal distribution of education levels from high school only to
      graduate school. The majority of patients received care through cancer centers
      (96.7%), with a split between academic and non-academic centers. Ninety-three
      percent of patients had radiation therapy as part of their treatment modality,
      with 70.3% having chemotherapy and 60.1% having surgery. The most common system
      toxicities affected the oropharynx, followed by epithelium (skin/hair/nail), and
      then general global health. Specifically, the most common side effects were
      difficulty swallowing (61.5%) and changes in skin color/texture (49.7%). One
      third of patients experienced hearing/tinnitus/vertigo, xerostomia, loss of
      tissue flexibility, or fatigue. Conclusion: The current work demonstrates the
      ability to obtain patient-reported outcomes of head and neck cancer survivors
      through an Internet-based survivorship care plan program. For this group
      dysphagia and dermatitis were the most commonly reported toxicities, as was
      expected; however, global effects of therapy, such as fatigue, were also
      significant and should be addressed in future survivorship planning.

PMID- 30100774
TI  - Ten tips to encourage student interaction with screen-capture type vodcasts.
AB  - Video podcasts (vodcasts) are gaining popularity in medical education, but they
      can be a passive learning modality if students do not actively engage with the
      content. Of the two categories of vodcast software, screen-capture (mp4 output)
      and FlashTM (HTML5/Flash output), screen-capture has greater potential to result
      in passive learning because students cannot physically interact with the content.
      However, screen-capture offers several advantages for the producer (often
      faculty) and the consumer (students). As such, this type of software is popular
      with medical school faculty. To encourage active learning, ten tips are presented
      with specific strategies that faculty can use with screen-capture type vodcasts.
      Many of the tips also apply to Flash-type vodcasts. By incorporating these
      strategies, faculty with limited technical abilities can create engaging vodcasts
      that stimulate active learning.

PMID- 30100775
TI  - Current approaches and future directions in the treatment of leprosy.
AB  - This review surveys current treatments and future treatment trends in leprosy
      from a clinical perspective. The World Health Organization provides a multidrug
      treatment regimen that targets the Mycobacterium leprae bacillus which causes
      leprosy. Several investigational drugs are available for the treatment of drug
      resistant M. leprae. Future directions in leprosy treatment will focus on: the
      molecular signaling mechanism M. leprae uses to avoid triggering an immune
      response; prospective studies of the side effects experienced during multiple
      drug therapy; recognition of relapse rates post-completion of designated
      treatments; combating multidrug resistance; vaccine development; development of
      new diagnostic tests; and the implications of the recent discovery of a
      genetically distinct leprosy-causing bacillus, Mycobacterium lepromatosis.

PMID- 30100776
TI  - Monitoring the use of nifurtimox-eflornithine combination therapy (NECT) in the
      treatment of second stage gambiense human African trypanosomiasis.
AB  - After inclusion of the nifurtimox-eflornithine combination therapy (NECT) in the
      Model List of Essential Medicines for the treatment of second-stage gambiense
      human African trypanosomiasis (HAT), the World Health Organization, in
      collaboration with National Sleeping Sickness Control Programs and
      nongovernmental organizations set up a pharmacovigilance system to assess the
      safety and efficacy of NECT during its routine use. Data were collected for 1735
      patients treated with NECT in nine disease endemic countries during 2010-2011. At
      least one adverse event (AE) was described in 1043 patients (60.1%) and a total
      of 3060 AE were reported. Serious adverse events (SAE) were reported for 19
      patients (1.1% of treated), leading to nine deaths (case fatality rate of 0.5%).
      The most frequent AE were gastrointestinal disorders (vomiting/nausea and
      abdominal pain), followed by headache, musculoskeletal pains, and vertigo. The
      most frequent SAE and cause of death were convulsions, fever, and coma that were
      considered as reactive encephalopathy. Two hundred and sixty-two children below
      15 years old were treated. The characteristics of AE were similar to adults, but
      the major AE were less frequent in children with only one SAE and no deaths
      registered in this group. Gastrointestinal problems (vomiting and abdominal pain)
      were more frequent than in adults, but musculoskeletal pains, vertigo, asthenia,
      neuropsychiatric troubles (headaches, seizures, tremors, hallucinations,
      insomnia) were less frequent in children. Patient follow-up after treatment is
      continuing, but initial data could suggest that NECT is effective as only a low
      number of relapses have so far been reported (19 cases). However, additional
      monitoring is required to assess the efficacy of the treatment, particularly in
      children. NECT has given satisfactory results of safety in the usual conditions
      where HAT patients are managed and it is currently the best option for treatment
      of second stage of gambiense HAT.

PMID- 30100777
TI  - Melioidosis in acute cholangitis of diabetic patient: a forgotten diagnosis.
AB  - Melioidosis presents with a wide range of clinical presentations, which include
      severe community-acquired pneumonia, septicemia, central nervous system
      infection, and less severe soft tissue infection. Hence, its diagnosis depends
      heavily on the clinical microbiology laboratory for culture. In this case report,
      we describe an atypical presentation of melioidosis in a 52-year-old man who had
      fever, right upper-abdominal pain, and jaundice for 15 days. Melioidosis caused
      by Burkholderia pseudomallei was subsequently diagnosed from blood culture. As a
      primary care physician, high suspicion index is of great importance. High
      suspicion index of melioidosis in a high-risk group patient, such as the patient
      with diabetes mellitus and diabetic foot, is crucial in view of atypical
      presentations of pseudomonas sepsis. A correct combination of antibiotic
      administration in the early phase of therapy will determine its successful
      outcome.

PMID- 30100778
TI  - Diversity of human African trypanosomiasis epidemiological settings requires fine
      tuning control strategies to facilitate disease elimination.
AB  - In 2001, the World Health Organization (WHO) established a public-private
      partnership to fight human African trypanosomiasis (HAT). As a result of this
      continuous collaboration, and in addition to the coordination with
      nongovernmental organizations and bilateral cooperation agencies, the number of
      new cases of HAT annually reported by the WHO has strikingly decreased. In 2012,
      HAT was included in WHO's roadmap on neglected tropical diseases with a 2020
      target date for elimination. Although the prevalence of HAT is decreasing and its
      elimination is targeted, control approaches must be adapted to the different
      epidemiological patterns in order to adopt the most adequate strategies to
      maintain their cost-effectiveness. These strategies must be flexible and dynamic
      in order to be adapted to the disease progression, as well as to the changes
      affecting the existing health facilities in transmission areas, including their
      accessibility, their capabilities, and their involvement in the elimination
      process. Considering the different patterns of transmission (Trypanosoma brucei
      (T.b.) rhodesiense HAT) and transmission intensity (T.b. gambiense HAT),
      different settings have been defined. In the case of T.b. rhodesiense, this form
      exists primarily where wild animals are the main parasite reservoir, and where
      the main parasite reservoir is cattle. In T.b. gambiense, this form exists in
      areas with high intensity transmission, areas with moderate intensity
      transmission, and areas with low intensity transmission. Criteria and indicators
      must be established to monitor and evaluate the actions implemented toward the
      elimination of HAT.

PMID- 30100780
TI  - Validity of Neuropsychological Testing in Young African Children Affected by HIV.
AB  - Introduction: Western-constructed neuropsychological tests have been used in low
      and middle income countries to assess the impact of HIV/AIDS and other chronic
      illnesses. We explore using such instruments cross-culturally in a sub-Saharan
      Africa setting. Methods: IMPAACT P1104S was a two-year observational study
      carried out at six clinical sites (South Africa- 3 sites, Malawi, Uganda and
      Zimbabwe) to assess and compare neuropsychological outcomes in three cohorts of
      children 5-11 years of age: HIV-infected (HIV), HIV-exposed but uninfected (HEU)
      and HIV unexposed and uninfected (HU). Descriptive statistics compared socio
      demographic characteristics among children at sites. Instruments included the
      KABC-II cognitive ability, TOVA attention/impulsivity, BOT-2 motor proficiency
      tests, and BRIEF executive function problems. Test characteristics were assessed
      using intraclass and Spearman non-parametric correlations, linear regression and
      principal factor analyses. Results: Of the 611 participants, 50% were male and
      mean age ranged from 6.6 to 8 years. In Malawi, Uganda and Zimbabwe, substantial
      proportions of families lived in rural settings in contrast to the South African
      sites. Intraclass correlation coefficients between weeks 0 and 48 were highest
      for the KABC scores, ranging between 0.42 to 0.71.Correlations among similar test
      domains were low to moderate but significant, with positive correlation between
      KABC Sequential and TOVA scores and negative correlation between BRIEF and KABC
      scores. TOVA response time scores correlated negatively with the BOT-2 Total
      points score. Strong and significant associations between individual measures of
      growth, disability and development with all test scores were observed.
      Performance-based measures were markedly lower for HIV compared to HEU and HU
      participants, even after controlling for age, sex and site. Factor analyses
      confirmed the underlying theoretical structure of the KABC scaled item scores.
      Conclusion: The KABC, TOVA, BRIEF and BOT-2 were valid and reliable tools for
      assessing the neuropsychological impact of HIV in four sub-Saharan African
      countries.

PMID- 30100781
TI  - Ecto- and endo-parasitic monogeneans (Platyhelminthes) on cultured freshwater
      exotic fish species in the state of Morelos, South-Central Mexico.
AB  - An extensive parasitological study of 365 freshwater exotic fish specimens
      belonging to 13 species of seven families (Cichlidae, Cyprinidae, Osphronemidae,
      Pangasidae, Poeciliidae, Characidae, and Loricariidae) collected from 31
      Aquaculture Production Units (APU) from Central Mexico revealed the occurrence of
      29 ecto- and endo-parasitic monogeneans found on gills and stomachs:
      Cichlidogyrussclerosus, C.thurstonae, C.tilapiae, Cichlidogyrus sp. 1,
      Cichlidogyrus sp. 2, Enterogyruscoronatus, E.malmbergi, Gusseviaspiralocirra,
      Sciadicleithrumiphthimum, Sciadicleithrum sp., Scutogyruslongicornis (all
      Dactylogyridae), Gyrodactyluscichlidarum, and G.yacatli (Gyrodactylidae) on
      Oreochromisniloticus, Pterophyllumscalare and Hemichromis sp. (Cichlidae);
      Dactylogyrusbaueri, D.formosus, D.intermedius, D.vastator, D.extensus,
      Dactylogyrus sp. (all Dactylogyridae), and G.kobayashii on Carassiusauratus,
      Cyprinuscarpio and Ctenopharyngodonidella (Cyprinidae); Trianchoratusacleithrium
      and T.trichogasterium (Dactylogyridae) on Trichogastertrichopterus
      (Osphronemidae); Thaparocleiduscaecus, T.siamensis (Dactylogyridae), and
      Dactylogyridae sp. on Pangasianodonhypophthalmus (Pangasidae); G.poeciliae on
      Poeciliareticulata (Poeciliidae); Diaphorocleidusarmillatus (Dactylogyridae) on
      Gymnocorymbusternetzy (Characidae); Unilatusunilatus (Dactylogyridae) and
      Gyrodactylidae sp. on Hypostomus sp. (Loricariidae). The paramount importance of
      the establishment of these monogeneans due to the importation/exportation of non
      native ornamental and other exotic host fish species cultured for food in Mexico
      is briefly discussed. Quarantine is recommended for all transferred host species.

PMID- 30100782
TI  - Searching for shelter in a ferruginous cave? A new species of Pasipha from a
      plateau in the Brazilian savanna (Platyhelminthes, Tricladida).
AB  - In a fauna survey in the eastern margin of Serra do Espinhaco Plateau, in an area
      belonging to the Brazilian savanna (Cerrado phytophysiognomy), a land flatworm
      was sampled in a ferruginous cave. Anatomical and histological analyses indicated
      that it belongs to a new species of the genus Pasipha, which is herein described.
      The new species shows an almost homogenous dark brown dorsal pigmentation, eyes
      spreading over the dorsal surface, a collar-shaped pharynx, and a prostatic
      vesicle with two portions separated by a canal. It differs from similar species
      mainly by anatomical and histological details of the ejaculatory duct, as well as
      male and female atria. The flatworm shows no troglomorphic traits and was
      collected once in the entrance zone of the cave. Hence, despite representing the
      first land flatworm species described from a Neotropical cave, we consider that
      its occurrence in the cave is probably occasional, using it as a shelter.

PMID- 30100783
TI  - Ten new species of the spider genus Althepus Thorell, 1898 from Southeast Asia
      (Araneae, Ochyroceratidae).
AB  - Spiders of the genus Althepus Thorell, 1898 are found throughout Southeast Asia,
      notable for their long walking legs. Ten new species are reported in this paper
      from China, Indonesia, Laos and Myanmar: A.chengmenensis Li & Li, sp. n. (??),
      A.cheni Li & Li, sp. n. (??), A.gouci Li & Li, sp. n. (??), A.hongguangi Li & Li,
      sp. n. (??), A.phousalao Li & Li, sp. n. (??), A.qianhuang Li & Li, sp. n. (??),
      A.qingyuani Li & Li, sp. n. (?), A.sepakuensis Li & Li, sp. n. (??), A.xuae Li &
      Li, sp. n. (??) and A.yizhuang Li & Li, sp. n. (??). These species were found in
      cave entrances and among tree-buttresses, indicating the spiders have a
      preference for dark and moist environments. All types are deposited in the
      Institute of Zoology, Chinese Academy of Sciences in Beijing, China (IZCAS).

PMID- 30100779
TI  - Malaria and HIV coinfection in sub-Saharan Africa: prevalence, impact, and
      treatment strategies.
AB  - Malaria and HIV, two of the world's most deadly diseases, are widespread, but
      their distribution overlaps greatly in sub-Saharan Africa. Consequently, malaria
      and HIV coinfection (MHC) is common in the region. In this paper, pertinent
      publications on the prevalence, impact, and treatment strategies of MHC obtained
      by searching major electronic databases (PubMed, PubMed Central, Google Scholar,
      ScienceDirect, and Scopus) were reviewed, and it was found that the prevalence of
      MHC in SSA was 0.7%-47.5% overall. Prevalence was 0.7%-47.5% in nonpregnant
      adults, 1.2%-27.8% in children, and 0.94%-37% in pregnant women. MHC was
      associated with an increased frequency of clinical parasitemia and severe
      malaria, increased parasite and viral load, and impaired immunity to malaria in
      nonpregnant adults, children, and pregnant women, increased in placental malaria
      and related outcomes in pregnant women, and impaired antimalarial drug efficacy
      in nonpregnant adults and pregnant women. Although a few cases of adverse events
      have been reported in coinfected patients receiving antimalarial and
      antiretroviral drugs concurrently, available data are very limited and have not
      prompted major revision in treatment guidelines for both diseases. Artemisinin
      based combination therapy and cotrimoxazole are currently the recommended drugs
      for treatment and prevention of malaria in HIV-infected children and adults.
      However, concurrent administration of cotrimoxazole and sulfadoxine-pyrimethamine
      in HIV-infected pregnant women is not recommended, because of high risk of
      sulfonamide toxicity. Further research is needed to enhance our understanding of
      the impact of malaria on HIV, drug-drug interactions in patients receiving
      antimalarials and antiretroviral drugs concomitantly, and the development of
      newer, safer, and more cost-effective drugs and vaccines to prevent malaria in
      HIV-infected pregnant women.

PMID- 30100784
TI  - Ultrastructure of spermatozoa in three cicada species from China (Hemiptera,
      Cicadomorpha, Cicadidae).
AB  - The ultrastructure of mature spermatozoa of three cicada species, Subpsaltria
      yangi, Karenia caelatata, and Platypleura kaempferi, was investigated using
      epifluorescence and transmission electron microscopies. This is the first
      investigation of the sperm ultrastructure of species in the subfamily Tibicininae
      and the tribe Sinosenini, represented by S. yangi and K. caelatata, respectively.
      The three species all produce two or three types of spermatozoa with various
      lengths, viz., polymegaly. The centriolar adjunct of spermatozoa in S. yangi
      shows a granular substructure, which is different from that of other cicada
      species, suggesting that spermatozoa in Tibicininae may have their own
      characteristics in comparison with other cicadas. The centriolar adjunct of
      spermatozoa of K. caelatata displays characteristics similar to that of the
      Cicadinae. Combined with other morphological characters, it is reasonable to
      remove K. caelatata and its allies (i.e., Sinosenini) from Cicadettinae to
      Cicadinae. The study of sperm ultrastructure, particularly in the species of
      Tibicininae and Sinosenini, expands the spermatological research of Cicadidae and
      provides more information for phylogenetic analysis of Cicadidae.

PMID- 30100785
TI  - Morphology and molecular genetics reveal two new Leptobrachella species in
      southern China (Anura, Megophryidae).
AB  - Based on morphological and phylogenetic analyses (16S rRNA mtDNA), two new
      species of the genus Leptobrachella are described from southern China, namely
      L.yunkaiensis Wang, Li, Lyu & Wang, sp. n. from Dawuling Forest Station of
      Guangdong Province and L.wuhuangmontis Wang, Yang & Wang, sp. n. from Mt. Wuhuang
      of Guangxi Province. To date, the genus Leptobrachella contains 68 species, among
      which 13 species are known from China. The descriptions of the two new species
      further emphasize that the species diversity of the genus Leptobrachella from
      China is still highly underestimated and requires further investigations.

PMID- 30100786
TI  - Two new species of the bamboo-feeding genus Bambusicaliscelis Chen & Zhang, 2011
      from China (Hemiptera, Fulgoromorpha, Caliscelidae).
AB  - Two new species of the bamboo-feeding planthopper genus Bambusicaliscelis Chen &
      Zhang, 2011, B.flavus Chen & Gong, sp. n. and B.guttatus Chen & Gong, sp. n., are
      described and illustrated from China. The generic characteristics are redefined
      and photographs of the new species are provided. A checklist and a key to species
      of Bambusicaliscelis are also given.

PMID- 30100787
TI  - A taxonomic study of Muscidifurax Girault & Sanders from China (Hymenoptera,
      Chalcidoidea, Pteromalidae).
AB  - Five species of Muscidifurax Girault & Sanders (Hymenoptera: Pteromalidae) are
      studied from mainland China, of which three new species, M.similadanacus Xiao &
      Zhou, sp. n., M.sinesensilla Xiao & Zhou, sp. n., M.neoraptorellus Xiao & Zhou,
      sp. n., and one newly recorded species, M.adanacus Doganlar, are reported. All
      species have been reared from pupae of Muscadomestica Linnaeus. A key to Chinese
      Muscidifurax and illustrations of external features of the species are provided.

PMID- 30100788
TI  - A new species of Pupulina van Beneden, 1892 (Copepoda, Siphonostomatoida,
      Caligidae) from Aetobatuscf.narinari (Pisces, Myliobatidae) from the Pacific
      coast of Ecuador.
AB  - A new caligid copepod species, Pupulinamantensissp. n. is described based on
      female and male specimens collected from the gills of the myliobatid elasmobranch
      Aetobatuscf.narinari Euphrasen, 1790 captured off the Pacific coast of Ecuador.
      The new species has a unique combination of characters that diverges from its
      known congeners, including: (i) weakly developed posterolateral processes on the
      genital complex; (ii) large spines on posterior surface of maxilliped basis (iii)
      abdomen slender, unsegmented, approximately 1/2 length and 1/5 width of genital
      complex; (iv) third exopodal segment of leg II with single long naked spine
      adjacent to minute, naked lateral spine; (v) velum of leg II with adjacent patch
      of denticles; (vi) caudal rami slightly less than half the length of genital
      complex; (vii) post-antennal process with robust, posteriorly directed tine,
      sclerotized stump posterolaterally, and two multi-sensillate papillae located on
      or near base of process (viii) post-oral process oval. The overall prevalence of
      P.mantensissp. n. on its host was 37.5% and its mean abundance was 1.87 specimens
      per host. This is the second record of the genus Pupulina from Ecuador and the
      second record of Pupulina infecting rays of the Myliobatinae genus Aetobatus, of
      the subfamily Myliobatinae, after its discovery on A.ocellatus in Australia, thus
      confirming this expansion of its previously known host range to a new
      elasmobranch subfamily.

PMID- 30100789
TI  - Tetrablemmidae, a spider family newly recorded from Cambodia (Arachnida,
      Araneae).
AB  - The family Tetrablemmidae O. Pickard-Cambridge, 1873 is reported from Cambodia
      for the first time. Two species belonging to the genus Tetrablemma O. Pickard
      Cambridge, 1873 are documented as new to science: Tetrablemmakepensesp. n. (male,
      female) from Kep Province and Tetrablemmasokensesp. n. (male, female) from
      Battambang Province. Diagnoses, morphological descriptions, and comparative
      illustrations are provided.

PMID- 30100791
TI  - An enigmatic new species of Panorpa Linneaus from the Bashan Mountains
      (Mecoptera, Panorpidae).
AB  - A new species of Panorpidae, Panorpabashanicolasp. n., is described and
      illustrated from the Bashan Mountains in central China. The new species is
      characterized by the following characters: vertex black, with two pale
      longitudinal stripes and four pale rounded spots; vein 1A ending before the
      origin of Rs; meso- and metanotum pale, and the pale color extending to tergum
      III in V-shape; male epandrium emarginate distally in deep U-shape; hypovalves
      without basal stalk, completely represented by a pair of short hypovalves,
      extending to distal third of gonocoxite, with five black stout setae in distal
      portion; paramere simple, S-shaped; a bundle of long hairs between dorsal and
      ventral valves of aedeagus; dorsal valves of aedeagus much longer than ventral
      valves and curved ventrally, with distal portion foot-shaped; female medigynium
      twice as long as wide, with stout axis extending over one-third its length beyond
      main plate.

PMID- 30100790
TI  - A review of the Cholevinae from the island of Borneo (Coleoptera, Leiodidae).
AB  - The available knowledge of the round fungus beetle subfamily Cholevinae
      (Leiodidae) from the island of Borneo is reviewed, and the results of newly
      studied material presented. The currently known 30 species (of which 14 are newly
      described herein) represent the genera Micronemadus (one species), Catops (one
      species), Baryodirus (one species), Ptomaphaginus (14 species), and Ptomaphaminus
      (13 species). The following new species are described: Micronemadussondaicus
      Schilthuizen & Perreau, sp. n., Ptomaphaginusgrandis Schilthuizen & Perreau, sp.
      n., P.louis Schilthuizen & Perreau, sp. n., P.muluensis Schilthuizen & Perreau,
      sp. n., and P.isabellarossellini Schilthuizen, Njunjic & Perreau, sp. n., and
      Ptomaphaminuskinabatanganensis Njunjic, Schilthuizen & Perreau, sp. n.,
      P.testaceus Schilthuizen & Perreau, sp. n., P.nanus Schilthuizen & Perreau, sp.
      n., P.marshalli Schilthuizen & Perreau, sp. n., P.hanskii Schilthuizen & Perreau,
      sp. n., P.sarawacensis Schilthuizen & Perreau, sp. n., P.layangensis Schilthuizen
      & Perreau, sp. n., P.microphallus Schilthuizen & Perreau, sp. n., and P.alabensis
      Schilthuizen & Perreau, sp. n. It is expected that the cholevine biodiversity of
      Borneo is still far from completely known. Nonetheless, provisional
      identification keys to all species known so far are presented.

PMID- 30100792
TI  - A newly discovered biodiversity hotspot of many-plumed moths in the Mount
      Cameroon area: first report on species diversity, with description of nine new
      species (Lepidoptera, Alucitidae).
AB  - Fifteen species of many-plumed moths are recorded from the Mount Cameroon area,
      SW Cameroon, West Africa. Nine species: Alucitalongipenis Ustjuzhanin &
      Kovtunovich, sp. n., A.lidiya Ustjuzhanin & Kovtunovich, sp. n., A.ludmila
      Ustjuzhanin & Kovtunovich, sp. n., A.escobari Ustjuzhanin & Kovtunovich, sp. n.,
      A.mischenini Ustjuzhanin & Kovtunovich, sp. n., A.fokami Ustjuzhanin &
      Kovtunovich, sp. n., A.janeceki Ustjuzhanin & Kovtunovich, sp. n., A.besongi
      Ustjuzhanin & Kovtunovich, sp. n., and A.olga Ustjuzhanin & Kovtunovich, sp. n.,
      are described as new for science. Four species are recorded as new from Cameroon:
      A.acalyptra, A.chloracta, A.coffeina, and A.spicifera. By these records, the
      Mount Cameroon area has become the richest known Afrotropical locality for the
      Alucitidae, highlighting its tremendous value for biodiversity conservation.

PMID- 30100793
TI  - Cryptic species diversity in the Hypsolebiasmagnificus complex, a clade of
      endangered seasonal killifishes from the Sao Francisco River basin, Brazilian
      Caatinga (Cyprinodontiformes, Aplocheilidae).
AB  - A great diversity of animal species adapted to life in the semi-arid Caatinga of
      northeastern Brazil, including seasonal killifishes, has been reported in the
      last three decades. More recently, field and molecular data have shown a high
      occurrence of cryptic species. The killifish group herein analysed, the
      Hypsolebiasmagnificus species complex, is endemic to the middle and southern
      portion of the Caatinga, occupying about 120 km along the floodplains of the
      middle Sao Francisco River and some adjacent tributaries. Species of this complex
      are rare and presently considered threatened with extinction, being uniquely
      found in pools protected by trees and bushes. Single-locus delimitation methods
      were used to test species limits of populations displaying different colour
      patterns along the whole distribution of the complex. All analyses consistently
      supported the three nominal species and two new, herein described: H.gardneri
      Costa, sp. n., from the floodplains of the middle Sao Francisco River and
      H.hamadryades Costa, sp. n., from the Gorotuba River floodplains. The
      phylogenetic analysis highly supports H.hamadryades as sister to a clade
      comprising H.gardneri and H.harmonicus. Our field observations suggest that
      H.hamadryades is a miniature species. This study indicates that the H.magnificus
      complex comprises cryptic species apparently endemic to small areas and extremely
      vulnerable to environmental changes, deserving high concern.

PMID- 30100794
TI  - Tzeananiaceae, a new pleosporalean family associated with
      Ophiocordycepsmacroacicularis fruiting bodies in Taiwan.
AB  - The order Pleosporales comprises a miscellaneous group of fungi and is considered
      to be the largest order of the class Dothideomycetes. The circumscription of
      Pleosporales has undergone numerous changes in recent years due to the addition
      of large numbers of families reported from various habitats and with a large
      amount of morphological variation. Many asexual genera have been reported in
      Pleosporales and can be either hyphomycetes or coelomycetes. Phoma-like taxa are
      common and have been shown to be polyphyletic within the order and allied with
      several sexual genera. During the exploration of biodiversity of pleosporalean
      fungi in Taiwan, a fungal strain was isolated from mycelium growing on the
      fruiting body of an Ophiocordyceps species. Fruiting structures that developed on
      PDA were morphologically similar to Phoma and its relatives in having pycnidial
      conidiomata with hyaline conidia. The fungus is characterised by holoblastic,
      cylindrical, aseptate conidiogenous cells and cylindrical, hyaline, aseptate,
      guttulated, thin-walled conidia. Phylogenetic analysis based on six genes, ITS,
      LSU, rpb2, SSU, tef1 and tub2, produced a phylogenetic tree with the newly
      generated sequences grouping in a distinct clade separate from all of the known
      families. Therefore, a new pleosporalean family Tzeananiaceae is established to
      accommodate the monotypic genus Tzeanania and the species T.taiwanensis in
      Pleosporales, Dothideomycetes. The Ophiocordyceps species was identified as
      O.macroacicularis and this is a new record in Taiwan.

PMID- 30100795
TI  - Unravelling tumble and swirl in a unique water-analogue engine model.
AB  - Abstract: The in-cylinder flow prior to combustion is considered to be one of the
      most important aspects controlling the combustion process in an engine. More
      specifically, the large-scale structures present in the cylinder, so-called
      tumble and swirl, before compression are believed to play a major role into the
      mixing and combustion processes. Their development during the intake stroke and
      their final strength depend mainly (but not only) on the inlet port design. In
      the present study, the turbulent large-scale structures during the intake stroke
      are investigated in a unique water-analogue engine where inlet ports and valve
      timings can easily be configured and tested. The flow field in the cylinder
      volume is reconstructed through multi-planar stereoscopic particle image
      velocimetry measurements which reveal a wealth of vortical structures during the
      stroke's various phases. The aim of the present paper is to present and show
      results from a unique setup which can serve as a test bench for optimisation of
      inlet port designs to obtain a desired vortical pattern in the cylinder after the
      intake stroke is finished. This setup can simulate the intake stroke in a much
      more realistic way as compared to a through-flow setup with a fixed valve lift.
      Graphical Abstract: 

PMID- 30100796
TI  - Grain dormancy genes responsible for preventing pre-harvest sprouting in barley
      and wheat.
AB  - Pre-harvest sprouting (PHS) remains a long-standing problem for the production of
      barley (Hordeum vulgare) and wheat (Triticum aestivum) worldwide. Grain dormancy,
      a key trait for the prevention of PHS, controls the timing of germination.
      Discovery of the causal sequence polymorphisms (CSPs) that produce naturally
      occurring variation in dormancy will help improve PHS tolerance. The
      identification of CSPs for dormancy remains difficult, especially for barley and
      wheat, because they are the last major cereals to have their genomes sequenced.
      However, recent work has identified several important CSPs that play pivotal
      roles in fine-tuning the dormancy levels in barley and wheat cultivars. This
      review summarizes these recent advances, which can be directly applied in
      breeding programs to improve PHS tolerance. These recent findings indicate the
      possibility that barley and wheat cultivars grown in East Asia, where much rain
      falls during the harvest season, will be rich sources of alleles that confer
      strong dormancy, since these cultivars have been selected to cope with the
      regional climate. The newly discovered dormant alleles will be useful for
      improving PHS tolerance around the world, just as Reduced-height (Rht) alleles
      from Japanese wheat varieties contributed to yield increases for the Green
      Revolution.

PMID- 30100797
TI  - A novel QTL associated with rice canopy temperature difference affects stomatal
      conductance and leaf photosynthesis.
AB  - Canopy temperature can be a good indicator of stomatal conductance. To understand
      the genetic basis of phenotypic differences in stomatal conductance between
      average and high-yielding rice (Oryza sativa L.) cultivars, we conducted a
      quantitative trait locus (QTL) analysis of canopy temperature. We developed
      reciprocal series of backcross inbred lines (BC1F6) derived from a cross between
      the average-yielding japonica cultivar 'Koshihikari' and the high-yielding indica
      cultivar 'Takanari'. A stable QTL, qCTd11 (QTL for canopy temperature difference
      on chromosome 11) on the short arm of chromosome 11, accounted for 10.4 and 19.8%
      of the total phenotypic variance in the two lines; the 'Takanari' allele
      decreased the canopy temperature difference value. A chromosome segment
      substitution line carrying the Takanari qCTd11 showed a greater reduction in
      canopy temperature than 'Koshihikari', and had higher stomatal conductance and
      photosynthetic rate. These results suggest that qCTd11 is not only involved in
      canopy temperature, but is also involved in both stomatal conductance and
      photosynthetic rate.

PMID- 30100798
TI  - The production and characterization of a BoFLC2 introgressed Brassica rapa by
      repeated backcrossing to an F1.
AB  - Flowering time is an important agronomic trait for Brassica rapa crops, and
      previous breeding work in Brassica has successfully transmitted other important
      agronomic traits from donor species. However, there has been no previous attempts
      to produce hybrids replacing the original Brassica FLC alleles with alien FLC
      alleles. In this paper, we introduce the creation of a chromosome substitution
      line (CSSL) containing a homozygous introgression of Flowering Locus C from
      Brassica oleracea (BoFLC2) into a B. rapa genomic background, and characterize
      the CSSL line with respect to the parental cultivars. The preferential
      transmission of alien chromosome inheritance and the pattern of transmission
      observed during the production of the CSSLs are also discussed.

PMID- 30100799
TI  - Increasing branch and seed yield through heterologous expression of the novel
      rice S-acyl transferase gene OsPAT15 in Brassica napus L.
AB  - Branching is a predominant element in the plant architecture of Brassica napus L.
      and represents an important determinant of seed yield. OsPAT15 (OsDHHC1), a novel
      DHHC-type zinc finger protein gene, was reported to regulate rice plant
      architecture by altering the tillering. However, whether heterologous
      overexpression of the OsPAT15 gene from the monocot rice into the dicot B. napus
      L. would have the same effect on branching or seed yield is unknown. In this
      study, the DHHC-type zinc finger protein gene OsPAT15 was determined to have
      sulfur acyl transferase activity in the akr1Delta yeast mutant in a
      complementation experiment. Heterologously expressing OsPAT15 transgenic B. napus
      L. plants were obtained using the Agrobacterium-mediated floral-dip
      transformation method. As anticipated, OsPAT15 transgenic plants exhibited
      branching and seed yield. Compared with non-transgenic plants, OsPAT15 transgenic
      plants had increased primary branches (1.58-1.76-fold) and siliques (1.86-1.89
      fold), resulting in a significant increase in seed yield (around 2.39-2.51-fold).
      Therefore, overexpression of the sulfur acyl transferase gene OsPAT15 in B. napus
      L. could be used to increase seed yield and produce excellent varieties.

PMID- 30100800
TI  - Thermo-responsive allele of sucrose synthase 3 (Sus3) provides high-temperature
      tolerance during the ripening stage in rice (Oryza sativa L.).
AB  - High-temperature stress during the ripening stage leads to quality deterioration
      due to an increase in chalky grains in brown rice (Oryza sativa L.). In a
      previous study, we identified a QTL for Appearance quality of brown rice 1 (Apq1)
      using chromosome segment substitution lines of the indica cultivar 'Habataki' in
      the japonica cultivar 'Koshihikari' background and narrowed down the locus to a
      48-kb region on chromosome 7. To verify the function and mechanisms of this QTL
      in grain appearance, in this study, we fine-mapped the gene and conducted high
      temperature tolerance tests. As a result of the genetic mapping, we narrowed down
      the candidate region of Apq1 to a 19.4-kb region including three predicted genes.
      Among these, the temporal expression pattern of sucrose synthase 3 (Sus3)
      corresponded well with the high temperature-sensitive period during ripening, and
      expression of the 'Habataki' allele of Sus3 was increased under high-temperature
      condition. In addition, we transformed the 'Habataki' Sus3 gene into
      'Nipponbare', and the transformants obtained high-temperature tolerance.
      Therefore, we conclude that the causal gene underlying the QTL Apq1 is the thermo
      responsive Sus3 allele, and the increase in Sus3 expression under high
      temperature condition during ripening leads to high-temperature tolerance in
      rice.

PMID- 30100801
TI  - Neutral alleles at hybrid sterility loci of Oryza glaberrima from AA genome
      relatives in Genus Oryza.
AB  - Hybrid sterility between Oryza sativa and O. glaberrima is a main reproduction
      barrier when transferring the favorable alleles from O. glaberrima to O. sativa
      and it happens due to allelic interaction at sterility loci. Neutral alleles at
      each locus have the potential to overcome the sterility between the two
      cultivated rice species. In this study, an O. sativa cultivar Dianjingyou 1
      (DJY1) and its near-isogenic lines (NILs) harboring the single sterility allele
      S1-glab, S19-glab, S20-glab, S37-glab, S38-glab and S39-glab as the tested lines
      were crossed with O. glaberrima, O. rufipogon, O. nivara, O. glumaepatula, O.
      barthii, O. meridionalis and O. sativa so as to detect the neutral alleles of
      these loci. Pollen fertility was investigated in the paired F1s based on two
      seasons' result and genotypic segregation was also analyzed in some F2
      populations to confirm the results of pollen fertility investigation. The neutral
      alleles of S38-n and S39-n were identified based upon the pollen fertility and
      genotypic segregation analysis for the first time. The neutral alleles of
      sterility loci detected from present report have the potential to know of the
      nature of interspecific hybrid sterility, and to overcome the interspecific
      hybrid sterility between O. sativa and O. glaberrima.

PMID- 30100802
TI  - The effect of stem growth habit on single seed weight and seed uniformity in
      soybean (Glycine max (L.) Merrill).
AB  - The timing of flower formation and length of the seed-filling period of
      indeterminate growth soybean varieties vary more than those of determinate
      varieties (Glycine max (L.) Merrill). These variations have been hypothesized to
      affect single seed weight and its uniformity which determine the processing
      quality of soybean used in foods. We derived near isogenic lines (NILs) with
      different growth characteristics from an indeterminate line (donor parent) and
      three determinate lines with heavy seeds (recurrent parents), and evaluated the
      effects of growth habit on seed weight and its uniformity. Each NIL population
      consisting of five indeterminate and five determinate BC4F4 lines tested at two
      locations in two different years with two replications. Split-plot analysis of
      variance, with main-plot and sub-plot being cross combination and growth habit,
      respectively, showed that indeterminate varieties had slightly heavier seeds than
      determinate varieties and that there was no significant difference in uniformity
      of single seed weights. The effects of growth habit on seed uniformity was
      related to genetic background, but differences between the two growth
      characteristics were less than the differences among genetic background. This
      indicates that indeterminate growth habit did not much influence seed weight or
      its uniformity.

PMID- 30100803
TI  - Evaluation of female gamete fertility through histological observation by the
      clearing procedure in Lilium cultivars.
AB  - Lilies (Lilium spp.) are one of the most important floricultural crops. As most
      lily cultivars have originated from interspecific hybridization, they usually
      have complex genome composition and occasionally fail to develop normal gametes.
      Further improvement of lily cultivars by sexual crossing requires evaluation of
      gamete development and subsequent male and female fertility. Although male
      fertility is easily evaluated through microscopic observation after staining or
      by pollen culture for germination, evaluation of female fertility is difficult,
      because gametes develop inside an ovule within an ovary. Lilium species have the
      Fritillaria type of embryo sac, which, at maturity, consists of a haploid egg
      apparatus, including one haploid egg cell and two haploid synergids, two polar
      nuclei (one haploid nucleus and one triploid nucleus) and three triploid
      antipodal cells. Compared to the Polygonum type of embryo sac, composition of the
      embryo in the Fritillaria type of embryo sac is complex. We developed an
      efficient microscopic observation technique for ovules using the clearing
      procedure, which allowed us to categorize abnormal patterns of female gametes and
      to elucidate the frequency of abnormal female gamete development. The
      relationship among normal embryo sac, pollen stainability and seed formation in
      lily cultivars is discussed.

PMID- 30100804
TI  - Thirteen years under arid conditions: exploring marker-trait associations in
      Eucalyptus cladocalyx for complex traits related to flowering, stem form and
      growth.
AB  - We present an association analysis for seven key traits related to flowering,
      stem form and growth in Eucalyptus cladocalyx, a tree species suitable for low
      rainfall sites, using a long-term progeny trial with 49 open-pollinated maternal
      families in the southern Atacama Desert, Chile. The progeny trial was carried out
      in an arid environment with a mean annual rainfall of 152 mm. Simple sequence
      repeats (SSR) from a full consensus map of Eucalyptus were used for genotyping
      245 individual trees. Twenty-three significant marker-trait associations were
      identified, explaining between 5.9 and 23.7% of the phenotypic variance. The
      marker EMBRA101 located on LG10 at 56.5 cM was concomitantly associated with
      diameter at breast height and tree height. Nine SSR were significantly associated
      with stem forking and stem straightness, explaining between 5.9 and 14.8% of the
      phenotypic variation. To our knowledge, this is the first study reporting a SSR
      based association mapping analysis for stem form traits in Eucalyptus. These
      results provide novel and valuable information for understanding the genetic base
      of key traits in E. cladocalyx for breeding purposes under arid conditions.

PMID- 30100805
TI  - Genome re-sequencing, SNP analysis, and genetic mapping of the parental lines of
      a commercial F1 hybrid cultivar of Chinese cabbage.
AB  - The genome-wide characterization of single nucleotide polymorphism (SNP) between
      cultivars or between inbred lines contributes to the creation of genetic markers
      that are important for plant breeding. Functional markers derived from
      polymorphisms within genes that affect phenotypic variation are especially
      valuable in plant breeding. Here, we report on the genome re-sequencing and
      analysis of the two parental inbred lines of the commercial F1 hybrid Chinese
      cabbage cultivar "W77". Through the genome-wide identification and classification
      of the SNPs and indels present in each parental line, we identified about 1,500
      putative non-functional genes in each parent. We designed cleaved amplified
      polymorphic sequence (CAPS) markers using specific mutations found at Eco RI
      restriction sites in the parental lines and confirmed their Mendelian segregation
      by constructing a linkage map using 96 F2 plants derived from the F1 hybrid
      cultivar, "W77". Our results and data will be a useful genomic resource for
      future studies of gene function and metagenomic studies in Chinese cabbage.

PMID- 30100806
TI  - Easy sectioning of whole grain of rice using cryomicrotome.
AB  - To obtain a clear intact section of a ripened rice grain, which is suitable for
      biochemical and histological analysis, the Kawamoto method using a specific
      adhesive film was applied using a cryomicrotome. The longitudinal and sagittal
      sections were easily obtained together with the cross-section, and cell
      characteristics were clearly discerned in the ripened grain. It was demonstrated
      that the Kawamoto method is readily applicable for intact sectioning of hard
      tissue, including ripened grain. Intact section sampling may be useful for
      enzymatic analysis and transcriptomic analysis of plant tissue.

PMID- 30100807
TI  - Resynthesis of Brassica juncea for resistance to Plasmodiophora brassicae
      pathotype 3.
AB  - The oilseed crop Brassica juncea carries many desirable traits; however,
      resistance to clubroot disease, caused by Plasmodiophora brassicae, is not
      available in this species. We are the first to report the clubroot resistant
      resynthesized B. juncea lines, developed through interspecific crosses between a
      clubroot resistant B. rapa ssp. rapifera and two susceptible B. nigra lines, and
      the stability of the resistance in self-pollinated generations. The interspecific
      nature of the resynthesized B. juncea plants was confirmed by using A- and B
      genome specific SSR markers, and flow cytometric analysis of nuclear DNA content.
      Self-pollinated progeny (S1 and S2) of the resynthesized B. juncea plants were
      evaluated for resistance to P. brassicae pathotype 3. The S1 and S2 progenies of
      one of the resynthesized B. juncea lines were resistant to this pathotype.
      However, resistance was lost in 6 to 13% plants of the S2 progenies derived from
      the second resynthesized B. juncea line; this apparently resulted from the loss
      of the genomic region carrying resistance due to meiotic anomalies.

PMID- 30100808
TI  - A new agent for derivatizing carbonyl species used to investigate limonene
      ozonolysis.
AB  - A new method for derivatizing carbonyl compounds is presented. The conversion of
      a series of dicarbonyls to oximes in aqueous solution and from gas-phase sampling
      was achieved using O-tert-butyl-hydroxylamine hydrochloride (TBOX). Some
      advantages of using this derivatization agent include: aqueous reactions, lower
      molecular weight oximes, and shortened oxime-formation reaction time.
      Additionally, the TBOX derivatization technique was used to investigate the
      carbonyl reaction products from limonene ozonolysis. With ozone (O3) as the
      limiting reagent, four carbonyl compounds were detected: 7-hydroxy-6-oxo-3-(prop
      1-en-2-yl)heptanal; 3-Isopropenyl-6-oxoheptanal (IPOH), 3-acetyl-6-oxoheptanal
      (3A6O) and one carbonyl of unknown structure. Using cyclohexane as a hydroxyl
      (OH*) radical scavenger, the relative yields (peak area) of the unknown carbonyl,
      IPOH, and 3A6O were reduced indicating the influence secondary OH radicals have
      on limonene ozonolysis products. The relative yield of the hydroxy-dicarbonyl
      based on the chromatogram was unchanged suggesting it is only made by the
      limonene + O3 reaction. The detection of 3A6O using TBOX highlights the
      advantages of a smaller molecular weight derivatization agent for the detection
      of multi-carbonyl compounds. The use of TBOX derivatization if combined with
      other derivatization agents may address a recurring need to simply and accurately
      detect multi-functional oxygenated species in air.

PMID- 30100809
TI  - Bayesian inference of spreading processes on networks.
AB  - Infectious diseases are studied to understand their spreading mechanisms, to
      evaluate control strategies and to predict the risk and course of future
      outbreaks. Because people only interact with few other individuals, and the
      structure of these interactions influence spreading processes, the pairwise
      relationships between individuals can be usefully represented by a network.
      Although the underlying transmission processes are different, the network
      approach can be used to study the spread of pathogens in a contact network or the
      spread of rumours in a social network. We study simulated simple and complex
      epidemics on synthetic networks and on two empirical networks, a social/contact
      network in an Indian village and an online social network. Our goal is to learn
      simultaneously the spreading process parameters and the first infected node,
      given a fixed network structure and the observed state of nodes at several time
      points. Our inference scheme is based on approximate Bayesian computation, a
      likelihood-free inference technique. Our method is agnostic about the network
      topology and the spreading process. It generally performs well and, somewhat
      counter-intuitively, the inference problem appears to be easier on more
      heterogeneous network topologies, which enhances its future applicability to real
      world settings where few networks have homogeneous topologies.

PMID- 30100810
TI  - Interfacial waveforms in chiral lattices with gyroscopic spinners.
AB  - We demonstrate a new method of achieving topologically protected states in an
      elastic hexagonal system of trusses by attaching gyroscopic spinners, which bring
      chirality to the system. Dispersive features of this medium are investigated in
      detail, and it is shown that one can manipulate the locations of stop-bands and
      Dirac points by tuning the parameters of the spinners. We show that, in the
      proximity of such points, uni-directional interfacial waveforms can be created in
      an inhomogeneous lattice and the direction of such waveforms can be controlled.
      The effect of inserting additional soft internal links into the system, which is
      thus transformed into a heterogeneous triangular lattice, is also investigated,
      as the hexagonal lattice represents the limit case of the heterogeneous
      triangular lattice with soft links. This work introduces a new perspective in the
      design of periodic media possessing non-trivial topological features.

PMID- 30100811
TI  - Providing sustainable catalytic solutions for a rapidly changing world.

PMID- 30100813
TI  - Fairness versus efficiency: how procedural fairness concerns affect coordination.
AB  - We investigate in a laboratory experiment whether procedural fairness concerns
      affect how well individuals are able to solve a coordination problem in a two
      player Volunteer's Dilemma. Subjects receive external action recommendations,
      either to volunteer or to abstain from it, in order to facilitate coordination
      and improve efficiency. We manipulate the fairness of the recommendation
      procedure by varying the probabilities of receiving the disadvantageous
      recommendation to volunteer between players. We find evidence that while
      recommendations improve overall efficiency regardless of their implications for
      expected payoffs, there are behavioural asymmetries depending on the
      recommendation: advantageous recommendations are followed less frequently than
      disadvantageous ones and beliefs about others' actions are more pessimistic in
      the treatment with recommendations inducing unequal expected payoffs.

PMID- 30100814
TI  - Effects of inclusion of cetirizine hydrochloride in beta-cyclodextrin.
AB  - Following the preparation of inclusion complex of cetirizine (CTZ) and beta
      cyclodextrin (beta-CD), the compound was investigated to assess the possibility
      of modifying the physicochemical properties (solubility, release, stability,
      permeability) of CTZ after complexation that are vital for subsequent formulation
      studies involving the said complex. Changes in FT-IR/Raman spectra, DSC
      thermograms and XRD diffractograms confirmed the formation of a CTZ-beta-CD
      system. Hydrophilic interaction chromatography with a DAD detector was employed
      to determine alterations of the CTZ concentration during studies following
      complexation. An analysis of a phase-solubility diagram of cCTZ = fcbeta-CD
      indicated a linear rise in the solubility of CTZ as the concentration of beta-CD
      increased. The inclusion of CTZ in a system with beta-CD significantly reduced
      the instability of CTZ in the presence of oxidizing factors. It was also found
      that regardless of the pH of the acceptor fluids used in the release studies an
      increase was observed in the concentration of CTZ in CD system compared to its
      free form. The ability to permeate artificial biological membranes manifested by
      CTZ after complexation was enhanced as well. In summary, CD has significant
      potential to mask the bitter taste of CTZ and to counter the instability induced
      by oxidizing factors.

PMID- 30100815
TI  - Static and slowly rotating neutron stars in scalar-tensor theory with self
      interacting massive scalar field.
AB  - Binary pulsar observations and gravitational wave detections seriously
      constrained scalar-tensor theories with massless scalar field allowing only small
      deviations from general relativity. If we consider a nonzero mass of the scalar
      field, though, significant deviations from general relativity are allowed for
      values of the parameters that are in agreement with the observations. In the
      present paper we extend this idea and we study scalar-tensor theory with massive
      field with self-interaction term in the potential. The additional term suppresses
      the scalar field in the neutron star models in addition to the effect of the mass
      of the scalar field but still, large deviations from pure GR can be observed for
      values of the parameters that are in agreement with the observations.

PMID- 30100817
TI  - Public opinion on human rights in Putin-era Russia: Continuities, changes, and
      sources of variation.
AB  - Major setbacks in the protection of human rights during the Putin regime have
      produced little public outcry, suggesting that there is scant support for human
      rights in Russian public opinion. However, analysis of survey data spanning 2001
      2015 yields several surprising conclusions. In contrast to findings from earlier
      studies, the data indicate that Russians think of rights in two distinct
      dimensions: material rights (including economic rights and rights of personal
      integrity) and (conventionally understood) civil liberties. Support for the
      former has been strong throughout the Putin era, and support for the latter has
      grown steadily and consistently. Moreover, support for civil liberties has
      increased most among less-educated and younger Russians who do not reside in
      Moscow and St. Petersburg: Contrary to theoretical expectations, variation in
      support has become less systematically linked to standard socioeconomic and
      demographic variables. Russians are divided over whether political NGOs should be
      allowed to receive foreign funding, a major issue for human rights advocates
      given the Russian government's crackdown on such funding and on human rights
      NGOs.

PMID- 30100816
TI  - Patient safety culture in nursing homes - a cross-sectional study among nurses
      and nursing aides caring for residents with diabetes.
AB  - Background: Due to the high morbidity and disability level among diabetes
      patients in nursing homes, the conditions for caregivers are exceedingly complex
      and challenging. The patient safety culture in nursing homes should be evaluated
      in order to improve patient safety and the quality of care. Thus, the aim of this
      study was to examine the perceptions of patient safety culture of nursing
      personnel in nursing homes, and its associations with the participants' (i)
      profession, (ii) education, (iii) specific knowledge related to their own
      residents with diabetes, and (iv) familiarity with clinical diabetes guidelines
      for older people. Methods: Cross-sectional survey design. The study included 89
      nursing home personnel (38 registered nurses and 51 nurse aides), 25 (28%) with
      advanced education, at two nursing homes. We collected self-reported
      questionnaire data on age, profession, education and work experience, diabetes
      knowledge and familiarity with diabetes guidelines. In addition, we applied the
      Nursing Home Survey on Patient Safety Culture instrument, with 42 items and 12
      dimensions. Results: In general, those with advanced education scored higher in
      all patient safety culture dimensions than those without, however statistically
      significant only for the dimensions "teamwork" (mean score 81.7 and 67.7, p =
      0.042) and "overall perceptions of resident safety" (mean score 90.0 and 74.3, p
      = 0.016). Nursing personnel who were familiar with diabetes guidelines for older
      people had more positive perceptions in key areas of patient safety culture, than
      those without familiarity with the guidelines. Conclusions: The findings from
      this study show that advanced education and familiarity with current diabetes
      guidelines was related to adequate evaluations on essential areas of patient
      safety culture in nursing homes.

PMID- 30100812
TI  - Engineering vascularized and innervated bone biomaterials for improved skeletal
      tissue regeneration.
AB  - Blood vessels and nerve fibers are distributed throughout the entirety of
      skeletal tissue, and play important roles during bone development and fracture
      healing by supplying oxygen, nutrients, and cells. However, despite the
      successful development of bone mimetic materials that can replace damaged bone
      from a structural point of view, most of the available bone biomaterials often do
      not induce sufficient formation of blood vessels and nerves. In part, this is due
      to the difficulty of integrating and regulating multiple tissue types within
      artificial materials, which causes a gap between native skeletal tissue.
      Therefore, understanding the anatomy and underlying interaction mechanisms of
      blood vessels and nerve fibers in skeletal tissue is important to develop
      biomaterials that can recapitulate its complex microenvironment. In this
      perspective, we highlight the structure and osteogenic functions of the vascular
      and nervous system in bone, in a coupled manner. In addition, we discuss
      important design criteria for engineering vascularized, innervated, and
      neurovascularized bone implant materials, as well as recent advances in the
      development of such biomaterials. We expect that bone implant materials with
      neurovascularized networks can more accurately mimic native skeletal tissue and
      improve the regeneration of bone tissue.

PMID- 30100818
TI  - Lower urinary tract infections from external beam radiation therapy in prostate
      cancer: A single institution experience.
AB  - External beam radiation therapy (EMRT) is effective for the treatment of
      localized prostate cancer. Lower urinary tract infections (LUTIs) are considered
      one of the main possible adverse events related to External beam radiation
      therapy. Here we analyzed the incidence of LUTI during EMRT. Urinary tract
      infection was assumed when the findings of bacteriuria exceeded 100,000 units/mL,
      accompanied by specific cystitis symptoms. Among the total 540 analyzed patient,
      208 (38.5%) developed a LUTI. E. coli was the main microorganism involved in
      LUTIs (102, 49.04%) with 8 cases of a combination between E. coli and another
      germ. In conclusion, a risk of urinary infections in cancer patients treated with
      pelvic radiotherapy was observed, in order to reduce the use of antibiotic
      resistance, preventive treatment with non-antibiotic agents 5 are warranted.

PMID- 30100820
TI  - Causes and Consequences of Social Exclusion and Peer Rejection Among Children and
      Adolescents.

PMID- 30100821
TI  - Machine learning: supervised methods.
AB  - Supervised learning algorithms extract general principles from observed examples
      guided by a specific prediction objective.

PMID- 30100819
TI  - Formation of a protein corona influences the biological identity of
      nanomaterials.
AB  - The development and testing of nanomaterials is an area of interest due to
      promising diagnostic and therapeutic applications in the treatment of diseases
      like cancer or cardiovascular disease. While extensive studies of the
      physicochemical properties of nanoparticles (NPs) are available, the
      investigation of the protein corona (PC) that is formed on NPs in biofluids is a
      relatively new area of research. The fact that few NPs are in clinical use
      indicates that the biological identity of NPs, which is in large part due to the
      PC formed in blood or other bodily fluids, may be altered in ways yet to be fully
      understood. Herein, we review the recent advances in PC research with the intent
      to highlight the current state of the field. We discuss the dynamic processes
      that control the formation of the PC on NPs, which involve the transient soft
      corona and more stable hard corona. Critical factors, like the environment and
      disease-state that affect the composition and stability of the PC are presented,
      with the intent of showcasing promising applications for utilizing the PC for
      disease diagnosis and the identification of disease-related biomarkers. This
      review summarizes the unique challenges presented by the nanoparticle corona and
      indicates future directions for investigation.

PMID- 30100822
TI  - Statistics versus machine learning.

PMID- 30100823
TI  - Interaction of Mannitol and Sucrose with Gellan Gum in Freeze-Dried Gel Systems.
AB  - The effect of sucrose and mannitol addition to low-acyl (LA) gellan gum gels at
      both the molecular and macroscopic levels prior to, and after freeze-drying has
      been investigated. It has been shown that the gel network order as well as the
      mechanical properties are changed with the solute content, especially in the case
      of sucrose. The freeze-dried gel structure, containing either mannitol or
      sucrose, was studied, reporting for the first time the interaction of mannitol
      with the gellan gum gel. The generated freeze-dried gel network was evaluated in
      terms of porosity, pore size and wall thickness distributions. The solute
      physical state was correlated the water activity trend as a function of the
      solute content. Since mannitol is crystalline, the water activity decreases, in
      contrast with the amorphous sucrose. The rehydration mechanism was investigated
      and associated with the solute release from the structure. Specifically, the
      material properties (surface and bulk) as well as the role of the dissolution
      medium over time were assessed. It was found that the rehydration for both the
      gellan/sucrose and gellan/mannitol systems was highly influenced by the additive
      content, as an increase in water uptake was measured up to 10 wt%. A further
      increase in solute led to a considerable drop in the rehydration rate and extent
      due to the change in the freeze-dried structure, with smaller pores and with
      higher wall thickness values.

PMID- 30100826
TI  - Characterization of the crystal structure, kinematics, stresses and rotations in
      angular granular quartz during compaction.
AB  - Three-dimensional X-ray diffraction (3DXRD), a method for quantifying the
      position, orientation and elastic strain of large ensembles of single crystals,
      has recently emerged as an important tool for studying the mechanical response of
      granular materials during compaction. Applications have demonstrated the utility
      of 3DXRD and X-ray computed tomography (XRCT) for assessing strains, particle
      stresses and orientations, inter-particle contacts and forces, particle fracture
      mechanics, and porosity evolution in situ. Although past studies employing 3DXRD
      and XRCT have elucidated the mechanics of spherical particle packings and angular
      particle packings with a small number of particles, there has been limited effort
      to date in studying angular particle packings with a large number of particles
      and in comparing the mechanics of these packings with those composed of a large
      number of spherical particles. Therefore, the focus of the present paper is on
      the mechanics of several hundred angular particles during compaction using in
      situ 3DXRD to study the crystal structure, kinematics, stresses and rotations of
      angular quartz grains. Comparisons are also made between the compaction response
      of angular grains and that of spherical grains, and stress-induced twinning
      within individual grains is discussed.

PMID- 30100825
TI  - In situ and real-time monitoring of structure formation during non-reactive
      sputter deposition of lanthanum and reactive sputter deposition of lanthanum
      nitride.
AB  - Lanthanum and lanthanum nitride thin films were deposited by magnetron sputtering
      onto silicon wafers covered by natural oxide. In situ and real-time synchrotron
      radiation experiments during deposition reveal that lanthanum crystallizes in the
      face-centred cubic bulk phase. Lanthanum nitride, however, does not form the
      expected NaCl structure but crystallizes in the theoretically predicted
      metastable wurtzite and zincblende phases, whereas post-growth nitridation
      results in zincblende LaN. During deposition of the initial 2-3 nm, amorphous or
      disordered films with very small crystallites form, while the surface becomes
      smoother. At larger thicknesses, the La and LaN crystallites are preferentially
      oriented with the close-packed lattice planes parallel to the substrate surface.
      For LaN, the onset of texture formation coincides with a sudden increase in
      roughness. For La, the smoothing process continues even during crystal formation,
      up to a thickness of about 6 nm. This different growth behaviour is probably
      related to the lower mobility of the nitride compared with the metal. It is
      likely that the characteristic void structure of nitride thin films, and the
      similarity between the crystal structures of wurtzite LaN and La2O3, evoke the
      different degradation behaviours of La/B and LaN/B multilayer mirrors for off
      normal incidence at 6.x nm wavelength.

PMID- 30100824
TI  - The International Mouse Phenotyping Consortium (IMPC): a functional catalogue of
      the mammalian genome that informs conservation.
AB  - The International Mouse Phenotyping Consortium (IMPC) is building a catalogue of
      mammalian gene function by producing and phenotyping a knockout mouse line for
      every protein-coding gene. To date, the IMPC has generated and characterised 5186
      mutant lines. One-third of the lines have been found to be non-viable and over
      300 new mouse models of human disease have been identified thus far. While
      current bioinformatics efforts are focused on translating results to better
      understand human disease processes, IMPC data also aids understanding genetic
      function and processes in other species. Here we show, using gorilla genomic
      data, how genes essential to development in mice can be used to help assess the
      potentially deleterious impact of gene variants in other species. This type of
      analyses could be used to select optimal breeders in endangered species to
      maintain or increase fitness and avoid variants associated to impaired-health
      phenotypes or loss-of-function mutations in genes of critical importance. We also
      show, using selected examples from various mammal species, how IMPC data can aid
      in the identification of candidate genes for studying a condition of interest,
      deliver information about the mechanisms involved, or support predictions for the
      function of genes that may play a role in adaptation. With genotyping costs
      decreasing and the continued improvements of bioinformatics tools, the analyses
      we demonstrate can be routinely applied.

PMID- 30100827
TI  - A crystallographic study of crystalline casts and pseudomorphs from the 3.5 Ga
      Dresser Formation, Pilbara Craton (Australia).
AB  - Crystallography has a long history of providing knowledge and methods for
      applications in other disciplines. The identification of minerals using X-ray
      diffraction is one of the most important contributions of crystallography to
      earth sciences. However, when the crystal itself has been dissolved, replaced or
      deeply modified during the geological history of the rocks, diffraction
      information is not available. Instead, the morphology of the crystal cast
      provides the only crystallographic information on the original mineral phase and
      the environment of crystal growth. This article reports an investigation of
      crystal pseudomorphs and crystal casts found in a carbonate-chert facies from the
      3.48 Ga-old Dresser Formation (Pilbara Craton, Australia), considered to host
      some of the oldest remnants of life. A combination of X-ray microtomography,
      energy-dispersive X-ray spectroscopy and crystallographic methods has been used
      to reveal the original phases of these Archean pseudomorphs. It is found with a
      high degree of confidence that the original crystals forming in Archean times
      were hollow aragonite, the high-temperature polymorphs of calcium carbonate,
      rather than other possible alternatives such as gypsum (CaSO4.2H20) and nahcolite
      (NaHCO3). The methodology used is described in detail.

PMID- 30100828
TI  - Finite Element Analysis of Impact for Helmeted and Non-helmeted Head.
AB  - This study investigated the influence of human head impact on the severity of
      traumatic brain injury. Simulation of the dynamic impact of a human head was
      performed using FEM (finite element method) and employing HIC (Head Injury
      Criterion). The study of traumatic brain injury included impacts with the
      occiput, temporal, forehead, and parietal part of the head, and the impact
      velocity at the surface ranged from 1 to 7 m/s. The following characteristics
      were considered and analyzed in the simulation: duration of the impact,
      intracranial pressure, HIC, and change in accelerations at the center of gravity
      of the brain. The computed distribution of pressure values in the brain during an
      impact confirmed the theory of inertial intracranial brain displacement. The
      effect of a protective helmet aimed at reducing the severity of traumatic brain
      injury was investigated, and a method to determine rational helmet parameters was
      developed. In the case of the protected head, impact acceleration occurred over a
      longer period of time, which yielded a reduction in the brain load compared to
      the unprotected head. The developed method allows us to predict the severity of
      traumatic brain injury (TBI) in the protected/unprotected human head and to
      provide recommendations for the determination of rational parameters for
      manufacturing personal protective equipment for the head.

PMID- 30100829
TI  - Comparative Biomechanical Analysis of Stress-Strain State of the Elbow Joint
      After Displaced Radial Head Fractures.
AB  - Radial head fractures are becoming a major public health problem and are an
      increasingly important target for both clinical and mechanical researchers. In
      this work, comparative biomechanical analyses of the stress-strain state of a
      healthy elbow joint and elbow joints with radial head compression from 2 to 5 mm
      due to injury are performed. Three-dimensional models of the elbow joint with
      cartilage surfaces and ligaments were constructed based on the results of
      computed tomography. This study is focused on an elbow joint range of motion
      ranging from 0 degrees  to 120 degrees  flexion. Analysis of the stress-strain
      state of cartilage and ligaments under the influence of functional loads is
      conducted using a finite element method (FEM) and the ABAQUS software package.
      The results show that with increasing compression of the radial head, contact
      stress increases at the olecranon, which can lead to cartilage damage. Analysis
      of displacement shows that compression of the radial head during full extension
      of the elbow joint leads to an increased humeral shift from 1.14 degrees  +/-
      0.22 in the healthy joint to 10.3 degrees  +/- 2.13 during 5-mm compression of
      the radial head. Mathematical modeling performed in this study proved that
      reducing the height of the radial head and the contact area between the radial
      head and the humeral head led to increased medial collateral ligament stresses of
      up to 36 +/- 3.8 MPa. This work confirmed that the head of the radius is the main
      stabilizing structure of the elbow joint and that the medial collateral ligament
      is the second structure responsible for valgus stability of the elbow joint.

PMID- 30100830
TI  - Host specificity of Asian parasitoids for potential classical biological control
      of Drosophila suzukii.
AB  - The Asian spotted wing drosophila, Drosophila suzukii, has recently become a
      serious pest of soft fruits in Europe. Classical biological control through the
      introduction of larval parasitoids from its native range in Asia is presently
      being considered. However, host specificity of potential biological control
      agents has to be determined to avoid releasing species that may have unintended
      non-target impacts. Larvae of six different European non-target fly species and
      the target D. suzukii were exposed either on diet or blueberries to three Asian
      larval parasitoids, Asobara japonica, Leptopilina japonica, and Ganaspis cf.
      brasiliensis, and one European species, Leptopilina heterotoma. Asobara japonica
      showed the lowest specificity, attacking and developing in all Drosophilidae.
      Leptopilina japonica successfully parasitized two non-target Drosophilidae, D.
      melanogaster and D. subobscura, with one singly progeny emerging from D.
      immigrans. Ganaspis cf. brasiliensis had the highest level of specificity but
      variations occurred between two geographical populations tested. A Japanese
      population was strictly specific to D. suzukii, whereas another population from
      China parasitized D. suzukii, D. melanogaster and sporadically D. subobscura. The
      European L. heterotoma successfully developed in D. melanogaster, D. subobscura
      and occasionally in D. immigrans, but nearly all eggs and larvae in D. suzukii
      were encapsulated. These results show that Ganaspis cf. brasiliensis is the
      species with the highest potential for biological control, but more studies are
      needed on its taxonomic status and the existence of biotypes or cryptic species
      varying in their specificity before field releases can be conducted in Europe.

PMID- 30100831
TI  - Identification of attractive blend for spotted wing drosophila, Drosophila
      suzukii, from apple juice.
AB  - Drosophila suzukii, commonly known as the spotted wing drosophila (SWD), is an
      exotic fruit fly from Southeast Asia that was introduced to the temperate regions
      of North America and Europe in 2008. It attacks a wide variety of fruits and has
      become a devastating pest of soft-skinned fruit crops. Due to the rapid spread of
      SWD across the newly invaded continents, fresh fruit markets have a zero
      tolerance policy regarding D. suzukii infestation. Specific and efficient D.
      suzukii detection tools are urgently needed so that farmers can deliver timely
      management interventions to meet market demands. Since SWD is known to be
      attracted to damaged and rotting fruits, headspace volatiles from fresh and
      fermented apple juices were collected and analyzed by gas chromatography-mass
      spectrometry. Special attention was given to the compounds produced and/or
      enriched during the fermentation process. After performing a series of laboataory
      and field tests, we identified a quinary blend, which is more efficient and
      selective for D. suzukii than the currently standard apple cider vinegar and
      commercially available SWD lure under field conditions. Identification of SWD
      attractant will help growers accurately detect D. suzukii adult infestations in
      orchards, thereby allowing for timely pest management interventions while
      reducing conventional insecticidal usage to protect our crops, environment, and
      ecosystem.

PMID- 30100833
TI  - Depression and chronic pain.

PMID- 30100832
TI  - Combining Sanford Arylations on Benzodiazepines with the Nuisance Effect.
AB  - 5-Phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-ones react under palladium- and
      visible light photoredox catalysis, in refluxing methanol, with aryldiazonium
      salts to afford the respective 5-(2-arylphenyl) analogues. With 2- or 4
      fluorobenzenediazonium derivatives, both fluoroaryl- and methoxyaryl- products
      were obtained, the latter resulting from a SNAr on the fluorobenzenediazonium
      salt ("nuisance effect"). A computational DFT analysis of the palladium-catalysed
      and the palladium/ruthenium-photocalysed mechanism for the functionalization of
      benzodiazepines indicated that, in the presence of the photocatalyst, the
      reaction proceeds via a low-energy SET pathway avoiding the high-energy oxidative
      addition step in the palladium-only catalysed reaction pathway.

PMID- 30100834
TI  - Representation of South Asian countries in five high-impact anesthesia journals.
AB  - Context: The South Asian region is comprised of eight countries, i.e., Pakistan,
      India, Bangladesh, Sri Lanka, Afghanistan, Bhutan, Nepal, and Maldives. There is
      dearth of literature documenting anesthesia research in this region. Aim: The aim
      of this audit was to look at research productivity in the region by examining the
      volume and the type of anesthesia publication in five high-index anesthesia
      journals. Settings and Design: The study design was a survey of literature in the
      top five high-impact anesthesiology journals carried out at a tertiary care
      hospital. Materials and Methods: The journal citation report 2016 was accessed to
      identify the top five anesthesia journals based on their impact factor. We
      identified articles published in these journals between January 2000 and December
      2015. Statistical Analysis: Microsoft Excel 2003 worksheet was used for data
      collection from extracted articles. Results: The highest number of publications
      came from India (n = 487) 95.9%; 58.5% of these were correspondence, 21% were
      original articles, 12.8% were case reports and case series, 1.2% reviews, and 1%
      editorials. Fourteen articles were published from Pakistan, with 1.2% original
      articles, 0.8% letter to editor, 0.6% audits, and 0.2% case reports. Nepal and
      Sri Lanka contributed seven publications. There were no publications in these
      journals from authors from Bangladesh, Afghanistan, Bhutan, and Maldives in the
      reviewed journals. The highest number of publications was equally distributed
      between two journals, i.e., "Anesthesia and Analgesia" (29.5%) and "Anesthesia"
      (28.9%). Conclusion: We found that scientific contributions from the South Asian
      region in terms of original anesthesiology research in five high index
      anesthesiology journals was suboptimal and has not shown an increasing trend over
      the last 16 years.

PMID- 30100835
TI  - Comparison between Critical-Care Pain Observation Tool and physiologic indicators
      for pain assessment in the critically ill, mechanically ventilated adult
      patients.
AB  - Background and Objectives: Pain assessment of nonverbal, critically ill patients
      continues to present a challenge in Intensive Care Unit (ICU). The Critical-Care
      Pain Observation Tool (CPOT) rates critically ill patients' pain based on
      clinical observation. In the present study, the accuracy of CPOT was compared
      with physiological indicators of pain in mechanically ventilated, critically ill
      patients. Methods: This quantitative prospective observational study was
      conducted to assess pain in the critically ill, mechanically ventilated patients
      in comparison to physiologic indicators such as blood pressure and heart rate. A
      repeated measures design was chosen, and a sample size of 180 was taken from 60
      patients with sepsis, acute exacerbations of chronic obstructive pulmonary
      disease, community-acquired pneumonia, and postsurgical patients in the ICU. The
      two painful procedures chosen were tracheal suction and patient positioning. The
      data were collected at rest, at tracheal suctioning, 20 min later at positioning
      of the patient, and final reading 20 min later. Three testing periods, each
      including 4 assessments for a total of 12 pain assessments with sixty patients,
      were completed during each patient's ICU course. A total of six assessments were
      done with the patient at rest and three each with pain stimulus of tracheal
      suctioning and patient positioning. Results: There was a significant increase in
      both hemodynamic variables (systolic blood pressure and diastolic blood pressure)
      during painful procedures except for the heart rate during positioning. The
      correlation between the CPOT and Ramsay scale was negative and significant.
      Conclusions: The present study provides evidence that the CPOT has good
      psychometric properties. It might prove useful for pain assessment in
      uncommunicative critically ill patients.

PMID- 30100837
TI  - Systemic lidocaine inhibits high-mobility group box 1 messenger ribonucleic acid
      expression and protein in BALB/c mice after closed fracture musculoskeletal
      injury.
AB  - Background: Severe musculoskeletal trauma can trigger an inflammatory response,
      and an excessive inflammatory response can lead to systemic inflammatory response
      syndrome and multiorgan failure. High-mobility group box 1 (HMGB1) is an early
      mediator pro-inflammatory cytokine in sterile injuries and a late cytokine
      mediator in infection and sepsis. Previous research has shown that administration
      of systemic lidocaine can inhibit HMGB1 expression in macrophages of septic rats.
      The aim of this study was to demonstrate the efficacy of systemic lidocaine to
      inhibit HMGB1 mRNA and protein in a BALB/c mouse model of sterile inflammation
      due to closed fracture musculoskeletal injury. Materials and Methods: Twenty
      adult male BALB/c mice were divided into lidocaine and control groups. The closed
      fracture musculoskeletal injury was performed by breaking the left thigh bone of
      the mice. Four hours after undergoing the closed fracture, the lidocaine group
      was treated with lidocaine intravenous (2 mg/kg). The same volume of distilled
      water was injected into the control group instead of lidocaine. HMGB1 mRNA
      expression was examined with real-time polymerase chain reaction, and HMGB1
      protein level was determined with enzyme-linked immunosorbent assay. Results: The
      expression of HMGB1 mRNA and protein levels in mice that sustained inflammation
      due to a closed fracture musculoskeletal injury was significantly decreased in
      the lidocaine group (P < 0.00 and P < 0.00 for mRNA and protein, respectively).
      Conclusions: Intravenous administration of lidocaine effectively inhibited the
      inflammatory process in BALB/c mice that underwent closed fracture
      musculoskeletal injury by suppressing HMGB1 mRNA transcription and HMGB1 protein
      translation.

PMID- 30100836
TI  - Epidemiology and risk factors for multidrug-resistant bacteria in critically ill
      patients with liver disease.
AB  - Background and Aims: The critically ill patients with liver disease are
      vulnerable to infections in both community and hospital settings. The nosocomial
      infections are often caused by multidrug-resistant (MDR) bacteria. The present
      observational study was conducted to describe the epidemiology, course, and
      outcome of MDR bacterial infection and identify the risk factors of such
      infection in critically ill patients with liver disease. Materials and Methods: A
      retrospective observational study was conducted on 106 consecutive critically
      patients with liver disease admitted in the Intensive Care Unit between March
      2015 and February 2017. The MDR and non-MDR (non-MDR) groups were compared and
      the risk factors identified by multivariate analysis. Results: Out of the 106
      patients enrolled in the study, 23 patients had infections caused by MDR
      bacteria. The MDR-infected patients had severe liver disease (Child-Pugh score 11
      +/- 2.3 vs. 7 +/- 3.9; P = 0.04), longer duration of antibiotic usage (6 +/- 2.7
      days vs. 2 +/- 1.5 days; P = 0.04), greater use of total parenteral nutrition
      (TPN) (73.9% vs. 62.6%; P = 0.04), and more concurrent antifungal administration
      (60.8% vs. 38.5%; P = 0.04). The mortality was higher in MDR group (hazard ratio
      = 1.86; P < 0.05). The independent predictors of MDR bacterial infection were
      Child-Pugh score >10, prior carbapenem use, antibiotic use for more than 10 days,
      TPN use, and concurrent antifungal administration. Conclusion: The study
      demonstrated a high prevalence of MDR bacterial infection in critically ill
      patients with a higher mortality over non-MDR bacterial infection and also
      identified the independent predictors of such infections.

PMID- 30100838
TI  - Intraperitoneal dexmedetomidine as an adjuvant to bupivacaine for postoperative
      pain management in children undergoing laparoscopic appendectomy: A prospective
      randomized trial.
AB  - Background and Aims: Intraperitoneal local anesthetic is an effective analgesic
      approach in laparoscopic appendectomy in adults. The aim of the study was to
      compare the postoperative pain when intraperitoneal bupivacaine is administered
      alone versus the addition of dexmedetomidine to it in children undergoing a
      laparoscopic appendectomy. Methods: In this prospective randomized trial, 52
      children were randomly allocated to Group B who received intraperitoneal
      bupivacaine 0.25% (2 mg/kg) or Group BD who received intraperitoneal bupivacaine
      0.25% (2 mg/kg) plus dexmedetomidine (1 mcg/kg) for postoperative analgesia in
      children undergoing laparoscopic appendectomy. Postoperative pethidine
      consumption at day 1 was recorded and considered the primary outcome of the
      study. Patients were evaluated for pain scores at 0, 2, 4, 6, 12, and 24 h, time
      to first request of pethidine, sedation scores at 0, 2, 4, and 6 h, length of
      hospital stay, and parents' satisfaction. Chi-square, Fisher's exact, Student's t
      test, and Mann-Whitney U-tests were used for analysis. Results: Postoperative
      visual analog scale scores were lower in Group BD at 2, 4, and 6 h (mean = 3, 3,
      3, respectively) compared with Group B (mean = 4, 5, 4, respectively) (P < 0.05).
      Patients in Group BD had more sedation scores at 0, 2, and 4 h (P < 0.05), longer
      time to first rescue analgesia (P = 0.03), lesser rescue analgesic consumption (P
      = 0.02), shorter length of hospital stay (P = 0.02), and higher parents'
      satisfaction (P = 0.01). Conclusion: Adding dexmedetomidine to intraperitoneal
      bupivacaine provides adequate postoperative analgesia in children undergoing
      laparoscopic appendectomy.

PMID- 30100839
TI  - Use of ultrasound-guided preoperative diaphragmatic thickness as a predictor of
      postoperative weaning failure in recipients and donors scheduled for living donor
      liver transplant surgery.
AB  - Background and Objectives: The present study was designed to explore the utility
      of ultrasound-guided diaphragmatic thickness in the preoperative period in
      healthy controls scheduled for live-related donor hepatectomy and patients
      suffering from chronic liver disease scheduled for liver transplantation (LT) and
      its use as a predictor of postoperative weaning failure. Materials and Methods:
      This prospective observational study was conducted in a tertiary health care
      center and 65 adult (18-70 years) participants (30 healthy liver donors and 35
      liver transplant recipients) were enrolled for this study. Right diaphragmatic
      thickness of both donors and recipients was measured by B-mode ultrasound using a
      10 MHz linear array transducer in the supine position in the operation theater
      just before induction of anesthesia. For subgroup analysis of the recipients, we
      further divided them into two groups - Group 1 (diaphragmatic thickness < 2 mm)
      and Group 2 (diaphragmatic thickness > 2 mm), and comparison was done for
      duration of mechanical ventilation. Intergroup comparison was made for duration
      of mechanical ventilation and various other parameters. Results: The sonographic
      measurement of diaphragm revealed that its thickness is decreased in patients
      with chronic liver disease patients (2.12 +/- 0.54 mm) as compared to healthy
      donors (3.70 +/- 0. 58 mm). On multiple logistic regression, higher duration of
      mechanical ventilation was associated with diaphragmatic thickness < 2 mm (Group
      1 of recipients) (adjusted odds ratio 0.86; 95% confidence interval: 0.75-0.99; P
      = 0.013) after adjusting for age, gender, and body mass index. Conclusions:
      Diaphragmatic thickness is decreased in patients with chronic liver disease as
      compared to healthy liver donors. Preoperative measurement of ultrasound-guided
      right hemidiaphragm thickness can be used to predict weaning failure in patients
      undergoing LT. Other studies are needed to confirm these finding on different
      group of patients.

PMID- 30100840
TI  - Ultrasound-guided bilateral superficial cervical plexus block for thyroid
      surgery: The effect of dexmedetomidine addition to bupivacaine-epinephrine.
AB  - Background: The thyroid gland surgery is a common and painful procedure demanding
      analgesia. Many regional techniques are applied for anterior neck surgeries
      mostly assigned in relation to the involved cervical fascia. Dexmedetomidine
      (Precedex) is a selective alpha 2 adrenoceptor agonist which prolongs the sensory
      blockade duration of local anesthetics. Our study hypothesis is that ultrasound
      (US)-guided bilateral superficial cervical plexus block (BSCPB) may provide
      longer analgesia when adding dexmedetomidine to bupivacaine-epinephrine. Purpose:
      The aim of this study is to evaluate the analgesic efficacy and possible side
      effects of US-guided BSCPB and the effect of dexmedetomidine addition to
      bupivacaine-epinephrine in patients undergoing thyroid surgery. Methods: This
      prospective, double-blind, randomized study was performed on 42 patients
      randomized into two equal groups each of 21; bupivacaine Group B and
      dexmedetomidine Group D. Patients with contraindications to regional anesthesia
      or uncontrolled comorbidities were excluded from the study. Total pethidine
      consumption in 24 h is the primary outcome. The visual analog scale, timing of
      the first opioid request, and hemodynamics are the secondary outcomes. Results:
      In Group D, there was a longer time to the first request of opioid
      postoperatively, a lower total pethidine consumption and pain score
      postoperatively, and lower fentanyl requirements intraoperatively. Conclusions:
      Sonographic-guided bilateral SCPB using a combination of bupivacaine,
      dexmedetomidine, and epinephrine was superior to bupivacaine for prolonged
      analgesia with less intra- and postoperative opioid consumption and lower side
      effect profile during thyroid surgery.

PMID- 30100841
TI  - Prevalence of depression and its association with sociodemographic factors in
      patients with chronic pain: A cross-sectional study in a tertiary care hospital
      in Saudi Arabia.
AB  - Introduction: Mental health issues, especially depression, are common in chronic
      pain patients. Depression affects these patients negatively and could lead to
      poor control of their pain. Some risk factors for both chronic pain and
      depression are known and need to be targeted as part of the management in a
      multidisciplinary approach. This study was conducted to estimate the prevalence
      of depression among chronic pain patients attending a pain clinic and to explore
      the association between depression in chronic pain patients and other factors
      such as sociodemographic features, number of pain sites, severity of pain, and
      types of pain. Methods: This is a cross-sectional study that carried out in a
      chronic pain clinic in a tertiary care hospital in Riyadh, Saudi Arabia (King
      Faisal Specialist Hospital and Research Centre). All chronic pain patients
      including cancer-related pain, apart from acute pain patients and children, were
      eligible to participate in the study. Association between depression and
      sociodemographic factors was assessed with univariate and multivariate methods.
      Main outcome measures were the prevalence of depression in chronic pain patients
      using the Patient Health Questionnaire-9 (PHQ-9) and the association with
      sociodemographic factors. Results: A total of 200 chronic pain patients (128
      females [64%]) participated in the study. The prevalence of depression was 71%
      (95% confidence interval: 64.7-77.3) based on the PHQ-9 diagnostic criteria using
      a cutoff point of >5. Among those patients who were depressed, 9 (4.5%) had
      severe depression as compared to 31 (15.5%), 41 (20.5%), and 61 (30.5%) who had
      moderately severe, moderate, and mild depression, respectively. Depression
      (scored at the cutoff point of 5) in chronic pain patients was significantly
      associated with age, financial status, medical history of depression, and pain
      severity. Conclusion: Depression is common among chronic pain patients with
      several risk factors aggravating its presentation. Due to their increased risk of
      depression, psychiatric counseling that offers mental health assistance should be
      prioritized and made available as a multidisciplinary approach for the treatment
      of chronic pain patients.

PMID- 30100842
TI  - Continuous psoas sciatic blockade for total knee arthroplasty.
AB  - Background: Psoas sciatic block (Pso/Sci) is a modern anesthetic technique for
      lower extremities surgery. The use of this technique can avoid the adverse
      effects of the general anesthesia or the central neuroaxial blockade, especially
      in patients with multiple comorbidities. Purpose: The purpose of this study is to
      compare the efficacy of combined Pso/sci as a sole anesthetic technique with
      conventional combined spinal epidural (CSE) anesthesia for patients undergoing
      total knee arthroplasty. Methods: Eighty patients scheduled for total knee
      replacement were included in the study. Patients were divided into two equal
      groups: Pso/sci group received ultrasound guided with the use of nerve locator
      continuous Pso/sci and the second group (CSE) received CSE anesthesia. Onset of
      sensory and motor block time, hemodynamic changes, contralateral spread, first
      time need for analgesia, incidence of complications, and patient and surgeon
      satisfactions were recorded. Results: The block time was significantly higher in
      the (Pso/Sci) group. Two patients in (Pso/Sci) had contralateral spread. Sensory
      and motor block onsets were delayed significantly in (Pso/Sci). Hemodynamic
      changes occurred in the CSE; however, it was insignificant compared to Pso/sci
      group. The first analgesic request was significantly later in (Pso/Sci) compared
      to the CSE group. There were no differences found in both groups as regard
      complications, early mobilization, and patients and surgeons satisfaction.
      Conclusions: Psoas sciatic block is an alternative safe and successful anesthetic
      technique, which can provide an adequate anesthesia for total knee surgery with
      less hemodynamic changes.

PMID- 30100843
TI  - Comparison of Macintosh, McCoy, and Glidescope video laryngoscope for intubation
      in morbidly obese patients: Randomized controlled trial.
AB  - Objectives: The aim of the study was to compare time to intubation and glottic
      visualization between Macintosh, McCoy, and Glidescope video laryngoscope (GVL)
      in morbidly obese patients. Methodology: Forty-five American Society of
      Anesthesiologists I-III morbidly obese patients were randomized into three groups
      of 15 each and time to intubation, Cormack-Lehane grading, and Intubation
      Difficulty Score (IDS) were compared. Results: GVL took more time to intubate
      (TTI) compared to Macintosh and McCoy laryngoscope (P = 0.0001). Overall IDS were
      similar between the groups. Conclusion: To conclude, GVL takes longer TTI with no
      added advantage in IDS and hemodynamic response to intubation in morbidly obese
      patients. McCoy is only as effective as Macintosh and hence Macintosh
      laryngoscope should be laryngoscope of choice due to its widespread availability
      and familiarity.

PMID- 30100844
TI  - Preoperative ketamine nebulization attenuates the incidence and severity of
      postoperative sore throat: A randomized controlled clinical trial.
AB  - Background: Endotracheal intubation is the prominent cause of airway mucosal
      injury which results in postoperative sore throat (POST), with an incidence of
      21%-65%. Although this complication is minor, if left unresolved, it produces
      significant agony and annoyance to the patient. This study was conducted to
      evaluate the efficacy of nebulized ketamine in decreasing POST. Materials and
      Methods: After written informed consent, 96 patients of the American Society of
      Anesthesiologists physical status (PS) 1-2 between 18 and 60 years, of either sex
      undergoing general anesthesia (GA) with tracheal intubation were enrolled in this
      prospective, randomized, placebo-control, and double-blind controlled trial.
      Patients were randomized into two groups; Group 1 received ketamine 50 mg (1.0
      ml) with 4.0 ml of saline nebulization, while Group 2 received saline
      nebulization 5.0 ml for 15 min. GA was administered 15 min after completing
      nebulization. On reaching postanesthesia care unit, POST monitoring was done at
      0, 2, 4, 6, 12, and 24 h after extubation. POST was graded on a four-point scale
      (0-3). Results: The overall incidence of POST in this study was 25%: POST was
      experienced by 7 patients (14.6%) in ketamine and 17 patients (35.4%) in saline
      group (Fisher's exact P = 0.018). There was statistically significant reduction
      in the incidence of POST in ketamine group when compared to saline, at 2, 4,
      6,12, and 24 h postoperatively (P < 0.05*). Severity of sore throat was also
      higher in saline group when compared to ketamine at 4 h (P = 0.030*) and 6 h (P =
      0.016*) postextubation. Conclusion: Preoperative ketamine nebulization
      effectively reduced the incidence and severity of POST, with no adverse effects.

PMID- 30100845
TI  - Adaptation of CARE (CAse REport) guidelines on published case reports in the
      Saudi Journal of Anesthesia.
AB  - Background: Toward improving the reporting quality of clinical case reports in
      the Saudi Journal of Anesthesia, we conducted this audit. The aim of this paper
      is to provide an overview of the different objectives for clinical case reports
      and to identify those subordinate items which seem most relevant from the CAse
      REport (CARE) checklist. Methods: We performed this pilot study on clinical case
      reports published in the Saudi Journal of Anesthesia (SJA) in the past 5 years
      from 2013 to 2017. The journal publishes 4 issues/year that means 20 issues were
      studied. We used one online source to gather the clinical case reports which is
      the SJA website. A total of 84 case reports were studied. We have applied the
      13th items in the CARE checklist on the case reports to determine their
      representations. Two reviewers abstracted data from all included papers to
      determine the adaptation of the CARE checklist. Data are presented as percentages
      of different subordinate items of the CARE guidelines. Results: None of the 84
      case reports met all subordinate items of CARE guidelines, and only 5 subordinate
      items were reported fully met (100%). Patient perspective subordinate item was
      not mentioned in our series due to lack of data in the studied case reports.
      Therefore, only 12 subordinate items were included. We reported those adaptation
      percentages of the 12th subordinate items of the CARE checklist as follows: (a)
      title, keywords, abstract patient's biodata, and conclusion 100%; (b) main
      symptoms of the patients 97.6%; (c) timeline 78.5%; (d) diagnosis 94.0%; (e)
      treatment 97.6%; (f) strengths 85.7%; (g) literature review 94.0%; and (h)
      patient consent 33.4%. Conclusion: We believe that the CAse REport guidelines can
      provide an international framework for the authors to follow in writing their
      case reports and for the editors to use to ensure the completeness and readiness
      of the peer-reviewed case reports for publication. For the SJA, we have to apply
      the CARE checklist and to ensure all subordinate items are adapted including the
      patient's perspective subordinate item and to make sure that the consent form
      obtained and accompanied each submitted case reports.

PMID- 30100846
TI  - Strategies to avoid empiric blood product administration in liver transplant
      surgery.
AB  - Massive blood loss has been a dreaded complication of liver transplantation, and
      the accompanying transfusion is associated with adverse outcomes in the form of
      decreased patient and graft survival. With advances in both surgical techniques
      and anesthetic management during transplantation, blood and blood products
      requirements reduced significantly. However, transfusion practices vary among
      different centers. The altered coagulation parameters in patients with liver
      cirrhosis results in a state of "rebalanced hemostasis" and patients are just as
      likely to clot as they are to bleed. Commonly used coagulation tests do not
      always reflect this new state and can, therefore, be misleading. Transfusion of
      blood products solely to correct abnormal parameters may worsen the coagulation
      status, thus adversely affecting patient outcome. Point-of-care tests such as
      thromboelastometry more reliably predict the risk of bleeding in these patients
      and in addition may provide quicker turnaround times compared to routine tests.
      Perioperative management should also include the possibility of thrombosis in
      these patients, and the use of low-molecular-weight heparin correlates with
      better patient survival. This review article aims to highlight the concept of
      rebalanced hemostasis, limitation of routine coagulation tests, and harmful
      effect of empiric transfusion of blood products.

PMID- 30100848
TI  - Pulmonary artery catheter entrapment after mitral valve surgery and the use of
      transesophageal echocardiography to accurately determine the site of entrapment.
AB  - The prevalence of pulmonary artery catheter (PAC) entrapment in open-heart
      surgery is scarce with a prevalence rate of 0.065%. Challenges in managing such
      cases lie particularly in choosing the modalities (chest roentgenogram,
      fluoroscopy, and transesophageal echocardiography) to accurately identify the
      anatomic location and cause of entrapment. In this case, we report a 42-year-old
      man who underwent mitral valve replacement with PAC entrapment discovered on
      postoperative day 2 and subsequently underwent retrieval after re-sternotomy.
      This case also highlights the usefulness of transesophageal echocardiography by
      the cardiac anesthetist in aiding the surgeons to locate the anatomic location
      where the catheter was entrapped.

PMID- 30100847
TI  - Lung ultrasound: Predictor of acute respiratory distress syndrome in intensive
      care unit patients.
AB  - Purpose: The purpose of the study was to review and summarize current literature
      concerning the validation and application of lung ultrasound (LUS) in critically
      ill patients with acute respiratory distress syndrome (ARDS). Materials and
      Methods: An extensive literature search was conducted using PubMed, Cochrane
      Review, Google Scholar, and Ohio State University Link based on the question if
      LUS should be considered a reliable investigational technique for ARDS diagnosis,
      treatment, and prognosis in pediatric and adult population. Results: LUS has been
      successfully validated for facilitating early diagnosis and diagnosis of
      simultaneous lung conditions, predicting lung recruitment treatment effect, and
      evaluating the prognosis in ARDS patients. Whether lung US is a useful tool in
      the prediction of prone position and oxygenation response in patients with ARDS
      is conflicting. Conclusions: LUS is a noninvasive, radiation-free, cheap, and
      easy to perform tool for critically ill patients with ARDS and might be a
      promising technique used in the Intensive Care Unit for ARDS management.

PMID- 30100850
TI  - Modified vertical infraclavicular block: An evaluation of two methods.
AB  - The vertical infraclavicular block (VIB) of the brachial plexus is commonly used
      to provide local anesthesia (LA) of the upper limb. The original method involves
      LA injection at the mid-point of an infraclavicular line between acromion and
      jugular fossa. However, this method is ineffective in adult patients with variant
      anatomy. Two modified VIB methods have been previously suggested. This
      prospective observational, clinical study compared both modified VIB approaches.
      The study showed that modified VIB is easy, efficacious, and applicable to all
      adult patients; including those with small stature, extreme tallness, or variant
      anatomy.

PMID- 30100849
TI  - Accidental discovery of a mass on the left main bronchus in a patient undergoing
      thyroid surgery.
AB  - A left lung mass after induction and tracheal intubation, which partially was
      obstructing the left main bronchus, was accidentally discovered in a 56-year-old
      female scheduled to undergo elective total thyroidectomy. Her preoperative chest
      X-ray showed a right-sided shift of the trachea. She did not have stridor or
      shortness of breath or superior vena cava obstructive syndrome. Induction and
      tracheal intubation were performed uneventfully. Fiberoptic bronchoscopy
      performed and showed complete obstruction on the left main bronchus. Excision
      biopsy suggested mucoepidermoid carcinoma (MEC). MEC is one of the very rare
      neoplasms of the lungs. Most lesions are low grade and overall prognosis may be
      more favorable than other forms of lung cancer.

PMID- 30100851
TI  - USG-guided continuous erector spinae block as a primary mode of perioperative
      analgesia in open posterolateral thoracotomy: A report of two cases.
AB  - The postoperative pain management in open thoracotomy is very crucial as the
      effective analgesia can prevent respiratory and thrombotic complications and lead
      to early mobilization and discharge. The thoracic epidural analgesia is the gold
      standard in such surgeries; however, there are few adverse effects such as
      hypotension, dural puncture, and contralateral block that always warrants safer
      alternative. Recently, with the advent of ultrasound, the regional anesthetic
      techniques are getting more popular to avoid such complications. Erector spinae
      plane (ESP) block is one of the novel techniques that has been described as a
      safe thoracic paravertebral block. We are reporting here the continuous ESP block
      as a primary mode of postoperative analgesia which was continued for 48 h. The
      intraoperative opioid requirement was very less, and the maximum NRS score in
      postoperative period was 4 at 12 h, which was well managed with multimodal
      analgesic regimen along with rescue doses of opioid.

PMID- 30100852
TI  - Anesthesiologist preference for postoperative analgesia in major surgery patients
      with obstructive sleep apnea.
AB  - Obstructive sleep apnea (OSA) is prevalent and presents perioperative challenges.
      There are guidelines regarding perioperative care of OSA, but analgesia
      management of OSA patients is inconsistent or inadequate. This is a study of the
      United Kingdom anesthesiologists' postoperative analgesia preferences for OSA
      patients. Overall, the 1st choice of main analgesia was continuous epidural local
      anesthetic (LA) without opioid, at 30% rate; P = 0.001. The 2nd choice was
      continuous epidural LA plus fentanyl, at 21% rate; P = 0.001. The 3rd choice was
      intrathecal diamorphine, at 19% rate; P = 0.001. The 4th choice was nerve block
      catheter LA infusion, at 13% rate; P = 0.001. The 5th choice was wound
      infiltration with LA +/- epinephrine, at 8% rate; P = 0.001. The 6th choice was
      systemic opioid, at 7% rate; P = 0.007. The 7th choice was systemic nonsteroidal
      anti-inflammatory drugs, at 2% rate; P = 0.001. The hospital setting or
      anesthesiologists' experience did not significantly impact analgesia choice: P
      =0.411. This study shows that current practice by anesthesiologists has a
      preference for regional or opioid-sparing analgesia for OSA patients. This safe
      approach conforms to guidelines and should be encouraged.

PMID- 30100853
TI  - Cardiac arrest despite optimal preloading of patient using ultrasonography-guided
      inferior vena cava indices under subarachnoid neuraxial blockade: A report of two
      cases.
AB  - Spinal anesthesia (SA) is utilized as an effective means of anesthesia and has an
      impressive safety record but it is not devoid of complications, and sometimes,
      the complications are as fatal as cardiac arrest. Although many factors are
      involved in etiology of cardiac arrest under SA, the vagal responses to the
      decreased preload are the most common culprits. We report two cases of cardiac
      arrest under SA; which happened despite our patient being adequately preloaded
      utilizing the ultrasonography-guided targeted volume therapy. The patients were
      successfully resuscitated with no neurological deficit.

PMID- 30100854
TI  - Anesthetic implications for coexisting cardiac capillary hemangioma and multiple
      coronary artery to pulmonary artery fistulas.
AB  - Abnormalities of the coronary vascular branches and cardiac hemangiomas represent
      together unusual clinical entities, with an incidence difficult to establish for
      the former as the vast majority of the patients with these anomalous vascular
      connections are usually asymptomatic and 2.8% for the latter. Symptomatic
      patients may develop dyspnea on exertion or chest pain secondary to a "coronary
      steal" phenomenon as part of the underlying pathophysiology of the disease. The
      authors report a case of a patient with concomitant cardiac capillary hemangioma
      with multiple coronary to pulmonary artery fistula connections that was
      successfully treated with surgical resection of the tumor and ligation of the
      fistula tracts. A comprehensive and balanced anesthesia management aimed to
      preserve tight hemodynamic stability to avoid increased myocardial demand and
      worsening of the coronary steal becomes essential in these patients.

PMID- 30100855
TI  - Anesthetic management of parasitic conjoined twins' separation surgery.
AB  - Parasitic twin is a rare form of conjoined twins with an incidence ranging from 1
      in 50,000 to 1,00,000 live births. In thoracopagus type, both hearts are joined
      together and often are associated with underlying congenital cardiac
      malformations. The separation surgery is a challenging task for both the surgeon
      as well as anesthetist due to the complexity of the procedure and long duration
      of surgery, carrying mortality close to 100% in case of significant cardiac
      fusion. Here, we are sharing anesthetic management of successful separation of a
      rare type of parasitic male conjoined twins who had connected hearts and common
      liver.

PMID- 30100856
TI  - Can intermittent pneumatic compression cause compartment syndrome?
AB  - We report a case of a 32-year-old male patient who developed unilateral lower
      limb compartment syndrome following a long surgical procedure during which
      intermittent pneumatic compression was used as deep-venous thrombosis
      prophylaxis. This complication of surgery is associated with significant
      morbidity. Previously published reports have suggested the possible risk factors
      and a way to reach a diagnosis at an early stage. The possible risk factors we
      present are the long operative time and the use of intermittent pneumatic
      compression as deep-vein thrombosis prophylaxis. These findings could be used to
      raise awareness in early diagnosis and treatment.

PMID- 30100857
TI  - Other clinical applications of videolaryngoscopy besides intubation.

PMID- 30100858
TI  - An unusual cause of right ventricular wall rupture during radiofrequency ablation
      of hepatocellular carcinoma.

PMID- 30100859
TI  - Dependent contrast venous pooling in cardiogenic shock on computed tomography
      imaging.

PMID- 30100860
TI  - Citalopram-induced ventricular tachycardia under general anesthesia.

PMID- 30100861
TI  - Schwartz-Jampel syndrome: Is risk of malignant hyperthermia the same as that of
      the general population?

PMID- 30100862
TI  - Bilateral ultrasound-guided erector spinae plane block for postoperative
      analgesia in choledochal cyst resection surgery.

PMID- 30100863
TI  - Anesthesia challenges for emergency surgery in a pediatric patient with
      congenital laryngomalacia.

PMID- 30100864
TI  - Continuous erector spinae plane local anesthetic infusion for perioperative
      analgesia in pediatric thoracic surgery.

PMID- 30100865
TI  - Fracture and embolization of intravenous cannula placed in external jugular vein:
      A rare complication.

PMID- 30100867
TI  - Noradrenaline Increases mEPSC Frequency in Pyramidal Cells in Layer II of Rat
      Barrel Cortex via Calcium Release From Presynaptic Stores.
AB  - Somatosensory cortex is innervated by afferents originating from the locus
      coeruleus which typically release noradrenaline. We tested if activation of
      presynaptic alpha1-adrenoceptors (AR) coupled to a Gq-mediated signaling cascade
      resulted in calcium (Ca2+) release from stores and thereby increased spontaneous
      transmitter release in rat barrel cortex. Adding 1-100 MUM noradrenaline (NA) or
      5 MUM cirazoline (CO), a alpha1-AR specific agonist, to the standard artificial
      cerebrospinal fluid increased the frequency of miniature excitatory postsynaptic
      currents (mEPSC) by 64 +/- 7% in 51% of pyramidal cells in layer II (responders)
      with no effect on the amplitude. In 42 responders, the mEPSC frequency during
      control was significantly smaller (39 +/- 2 vs. 53 +/- 4 Hz) and upon NA
      exposure, the input resistance (Rin) decreased (9 +/- 7%) compared to non
      responders. Experiments using CO and the antagonist prazosin revealed that NA
      acted via binding to alpha1-ARs, which was further corroborated by simultaneously
      blocking beta- and alpha2-ARs with propranolol and yohimbine, which did not
      prevent the increase in mEPSC frequency. To verify elements in the signaling
      cascade, both the phospholipase C inhibitor edelfosine and the membrane permeable
      IP3 receptor blocker 2-APB averted the increase in mEPSC frequency. Likewise,
      emptying Ca2+ stores with cyclopiazonic acid or the chelation of intracellular
      Ca2+ with BAPTA-AM prevented the frequency increase, suggesting that the
      frequency increase was caused by presynaptic store release. When group I
      metabotropic glutamate receptors were activated with DHPG, co-application of NA
      occluded a further frequency increase suggesting that the two receptor
      activations may not signal independently of each other. The increased mEPSC
      frequency in a subset of pyramidal cells results in enhanced synaptic noise,
      which, together with the reduction in Rin, will affect computation in the
      network.

PMID- 30100868
TI  - Inferring Evolutionary Process From Neuroanatomical Data.
AB  - Brain evolution has interested neuroanatomists for over a century. These
      interests often fall on how free the brain is to evolve independently of the
      body, how free brain regions are to evolve independently of each other, and how
      different environmental and ecological factors affect the brain over evolutionary
      time. But despite major advances in phylogenetic methods, comparative
      neuroanatomists have tended to limit their macroevolutionary toolbox to
      regression-based analyses and ignored the scope of evolutionary process-based
      models at their disposal. This Review summarizes the history of comparative
      neuroanatomy and highlights the pitfalls of the methodologies traditionally used.
      It provides an overview of evolutionary process-based modeling approaches for
      investigating univariate and multivariate data, as well as more sophisticated
      methods that incorporate hypotheses about biotic and abiotic pressures that may
      drive brain evolution. The benefits of evolutionary process-based models, and
      shortcomings of regression-based ones, are illustrated with widely used
      neuroanatomical data. Ultimately, the intent of this Review is to be a guide for
      subsuming macroevolutionary methods not typically used in comparative
      neuroanatomy, in order to improve our understanding of how the brain evolves.

PMID- 30100866
TI  - Noradrenergic Hypothesis Linking Neurodegeneration-Based Cognitive Decline and
      Astroglia.
AB  - In the past, manipulation of the cholinergic system was seen as the most likely
      therapeutic for neurodegeneration-based cognitive decline in Alzheimer's disease
      (AD) (Whitehouse et al., 1982). However, targeting the noradrenergic system also
      seems a promising strategy, since more recent studies revealed that in post
      mortem tissue from patients with AD and other neurodegenerative disorders there
      is a robust correlation between cognitive decline and loss of neurons from the
      Locus coeruleus (LC), a system with diffuse noradrenaline (NA) innervation in the
      central nervous system (CNS). Therefore, the hypothesis has been considered that
      increasing NA signaling in the CNS will prevent, or at least halt the progression
      of neurodegeneration and cognitive decline. A hallmark of the age- and
      neurodegeneration-related cognitive decline is reduced neurogenesis. We here
      discuss noradrenergic dysfunction in AD-related cognitive decline in humans and
      its potential involvement in AD pathology and disease progression. We also focus
      on animal models to allow the validation of the noradrenergic hypothesis of AD,
      including those based upon the immunotoxin-mediated ablation of LC based on
      saporin, a protein synthesis interfering agent, which offers selective and graded
      demise of LC neurons, Finally, we address how astrocytes, an abundant and
      functionally heterogeneous cell type of neuroglia maintaining homeostasis, may
      participate in the regulation of neurogenesis, a new strategy for preventing LC
      neuron loss.

PMID- 30100869
TI  - Good News or Bad News, Which Do You Want First? The Importance of the Sequence
      and Organization of Information for Financial Decision-Making: A Neuro-Electrical
      Imaging Study.
AB  - Investment decisions are largely based on the information investors received from
      the target firm. Thaler introduced the hedonic editing framework, in which
      suggests that integration/segregation of information influence individual's
      perceived value. Meanwhile, when evaluating the evidence and information in a
      sequence, order effect and biases have been found to have an impact in various
      areas. In this research, the influence of the Organization of Information
      (Integration vs. Segregation) and the Sequence of Information (Negative-Positive
      order vs. Positive-Negative order) on individual's investment decision-making
      both at the behavioral level (decision) and neurometrix level (measured by an
      individual's emotion and Approach Withdraw tendency) was assessed for the three
      groups of information: a piece of Big Positive Information and a piece of Small
      Negative Information, a piece of Big Negative Information and a piece of Small
      Positive Information, and a piece of Small Negative information. The behavioral
      results, which are an individual's final investment decision, were consistent for
      all three scenarios. In general, individuals will invest more/retire less when
      receiving two pieces of information in a Negative-Positive order. However, the
      neurometric results (Emotional Index, Approach Withdraw Index and results from
      LORETA) show differences among information groups. An effect of the Sequence of
      Information and the Organization of Information was found for the different
      scenarios. The results suggest that in the scenarios that involve large-scale
      information, the organization of information (Integration vs. Segregation)
      influences the emotion and Approach Withdraw tendency. The results of this
      investigation should provide insight for effective communication of information,
      especially when large-scale information is involved.

PMID- 30100871
TI  - Design and Evaluation of Passive Shoulder Joint Tracking Module for Upper-Limb
      Rehabilitation Robots.
AB  - As the number of people suffering from shoulder movement disabilities increases,
      there is a rising demand for shoulder rehabilitation. The natural motion of the
      shoulder joint [glenohumeral (GH) joint] includes not only three-degrees-of
      freedom (DOF) rotation but also three-DOF translation of the joint center due to
      simultaneous motion of the shoulder girdle. If the motion of the shoulder girdle
      is restricted, then the arm cannot be raised above a certain posture. This paper
      presents a passive shoulder joint tracking device that allows three-DOF
      translation of the shoulder joint while compensating for gravity. The single-DOF
      vertical tracker with a constant-force spring compensates for the gross weight of
      the user's arm, the upper limb rehabilitation device, and the tracker itself
      while allowing vertical tracking motion. The two-DOF horizontal tracker consists
      of two linear guides arranged perpendicular to each other. The tracker freely
      follows the shoulder joint in the horizontal plane. The effect of using the
      passive shoulder joint tracking device was evaluated by means of experiments by
      combining two popular commercial upper limb rehabilitation apparatuses with the
      proposed tracker. Nineteen subjects (8 healthy persons and 11 patients with
      shoulder impairments) participated in the evaluation study. The movement of the
      GH joint and the interactive force between the subject and the commercial
      rehabilitation device were analyzed when subjects made the following shoulder
      movements: flexion/extension and abduction/adduction. The improved tracker
      allowed a greater range of motion and reduced interaction. The tracker can be
      combined with existing commercial rehabilitation devices for more natural
      shoulder movement during rehabilitation tasks.

PMID- 30100870
TI  - A Glutamatergic Spine Model to Enable Multi-Scale Modeling of Nonlinear Calcium
      Dynamics.
AB  - In synapses, calcium is required for modulating synaptic transmission,
      plasticity, synaptogenesis, and synaptic pruning. The regulation of calcium
      dynamics within neurons involves cellular mechanisms such as synaptically
      activated channels and pumps, calcium buffers, and calcium sequestrating
      organelles. Many experimental studies tend to focus on only one or a small number
      of these mechanisms, as technical limitations make it difficult to observe all
      features at once. Computational modeling enables incorporation of many of these
      properties together, allowing for more complete and integrated studies. However,
      the scale of existing detailed models is often limited to synaptic and dendritic
      compartments as the computational burden rapidly increases when these models are
      integrated in cellular or network level simulations. In this article we present a
      computational model of calcium dynamics at the postsynaptic spine of a CA1
      pyramidal neuron, as well as a methodology that enables its implementation in
      multi-scale, large-scale simulations. We first present a mechanistic model that
      includes individually validated models of various components involved in the
      regulation of calcium at the spine. We validated our mechanistic model by
      comparing simulated calcium levels to experimental data found in the literature.
      We performed additional simulations with the mechanistic model to determine how
      the simulated calcium activity varies with respect to presynaptic-postsynaptic
      stimulation intervals and spine distance from the soma. We then developed an
      input-output (IO) model that complements the mechanistic calcium model and
      provide a computationally efficient representation for use in larger scale
      modeling studies; we show the performance of the IO model compared to the
      mechanistic model in terms of accuracy and speed. The models presented here help
      achieve two objectives. First, the mechanistic model provides a comprehensive
      platform to describe spine calcium dynamics based on individual contributing
      factors. Second, the IO model is trained on the main dynamical features of the
      mechanistic model and enables nonlinear spine calcium modeling on the cell and
      network level simulation scales. Utilizing both model representations provide a
      multi-level perspective on calcium dynamics, originating from the molecular
      interactions at spines and propagating the effects to higher levels of activity
      involved in network behavior.

PMID- 30100872
TI  - Forearm Motion Recognition With Noncontact Capacitive Sensing.
AB  - This study presents a noncontact capacitive sensing method for forearm motion
      recognition. A method is proposed to record upper limb motion information from
      muscle contractions without contact with human skin, compensating for the
      limitations of existing sEMG-based methods. The sensing front-ends are designed
      based on human forearm shapes, and the forearm limb shape changes caused by
      muscle contractions will be represented by capacitance signals. After
      implementation of the capacitive sensing system, experiments on healthy subjects
      are conducted to evaluate the effectiveness. Nine motion patterns combined with
      16 motion transitions are investigated on seven participants. We also designed an
      automatic data labeling method based on inertial signals from the measured hand,
      which greatly accelerated the training procedure. With the capacitive sensing
      system and the designed recognition algorithm, the method produced an average
      recognition of over 92%. Correct decisions could be made with approximately a 347
      ms delay from the relaxed state to the time point of motion initiation. The
      confounding factors that affect the performances are also analyzed, including the
      sliding window length, the motion types and the external disturbances. We found
      the average accuracy increased to 98.7% when five motion patterns were
      recognized. The results of the study proved the feasibility and revealed the
      problems of the noncontact capacitive sensing approach on upper-limb motion
      sensing and recognition. Future efforts in this direction could be worthwhile for
      achieving more promising outcomes.

PMID- 30100873
TI  - Evaluation of Metformin on Cognitive Improvement in Patients With Non-dementia
      Vascular Cognitive Impairment and Abnormal Glucose Metabolism.
AB  - Objective: Recent studies have suggested that metformin can penetrate the blood
      brain barrier, protecting neurons via anti-inflammatory action and improvement of
      brain energy metabolism. In this study, we aim to investigate the effect of
      metformin on cognitive function in patients with abnormal glucose metabolism and
      non-dementia vascular cognitive impairment (NDVCI). Methods: One hundred patients
      with NDVCI and abnormal glucose metabolism were randomly allocated into two
      groups: metformin and donepezil (n = 50) or acarbose and donepezil (n = 50). The
      neuropsychological status, glucose metabolism, and common carotid arteries intima
      media thickness (CCA-IMT) before and after a year of treatment, were measured and
      compared between the groups. Results: Ninety four patients completed all the
      assessment and follow-up. After a year of treatment, there was a decrease in
      Alzheimer's disease Assessment Scale-Cognitive Subscale scores and the duration
      of the Trail Making Test in the metformin-donepezil group. Furthermore, these
      patients showed a significant increase in World Health Organization-University of
      California-Los Angeles Auditory Verbal Learning Test scores after treatment (all
      P < 0.05). However, there was no obvious improvement in cognitive function in the
      acarbose-donepezil group. We also observed a significant decrease in the level of
      fasting insulin and insulin resistance (IR) index in the metformin-donepezil
      group, with a lower CCA-IMT value than that in the acarbose-donepezil group after
      a year of treatment (P < 0.05). Conclusion: We conclude that metformin can
      improve cognitive function in patients with NDVCI and abnormal glucose
      metabolism, especially in terms of performance function. Improved cognitive
      function may be related to improvement of IR and the attenuated progression of
      IMT. Trial Registration: ChiCTR-IPR-17011855.

PMID- 30100875
TI  - Serotonin 5-HT2C Receptor Activation Suppresses Binge Intake and the Reinforcing
      and Motivational Properties of High-Fat Food.
AB  - Binge eating disorder (BED) is characterized by dysfunctional hedonic food intake
      and reward-related processes. Activation of the serotonin (5-HT) 5-HT2C receptor
      (5-HT2CR) suppresses both food intake and reward-related behaviors and is thus
      poised to regulate BED. This study assessed the effects of 5-HT2CR activation via
      the selective 5-HT2CR agonist WAY163909 on binge eating-related behaviors in
      adult male Sprague-Dawley rats. Low doses of WAY163909 (1.0, 2.0 mg/kg)
      suppressed high-fat food (HFF) binge intake, but not standard food non-binge
      intake. WAY163909 (1.0 mg/kg) also attenuated operant responding for self
      administered HFF pellets on fixed and progressive ratio schedules of
      reinforcement, indicating that 5-HT2CR activation suppresses the reinforcing and
      motivational properties of HFF, respectively. These findings suggest that
      activation of the 5-HT2CR may be effective at suppressing binge eating in
      patients with BED via suppression of the reinforcing and motivational properties
      of HFF. This work supports future studies targeting the 5-HT2CR in the treatment
      of BED.

PMID- 30100876
TI  - Antiproliferative Properties of Newly Synthesized 19-Nortestosterone Analogs
      Without Substantial Androgenic Activity.
AB  - 19-Nortestosterone C-17 epimers with prominent antiproliferative properties have
      been previously described. In our present study, five novel 17alpha-19
      nortestosterones (3-7) were synthesized to increase their beneficial biological
      activities with no associated undesired hormonal effects. The compounds were
      screened by a viability assay against a panel of human adherent gynecological
      cancer cell lines. Three of the tested derivatives (3-5) exhibited a remarkable
      inhibitory effect on the proliferation of HeLa cells with IC50 values lower than
      that of our reference agent cisplatin (CIS). These three active agents also
      displayed considerable cancer selectivity as evidenced by their weaker growth
      inhibitory effect on non-cancerous fibroblast cells compared to CIS. The most
      potent newly synthesized 17alpha-chloro derivative (3) was selected for
      additional experiments in order to characterize its mechanism of action. Since
      nandrolone (19-nortestosterone, 1) is a structural analog with selective
      antiproliferative action on cervical carcinoma cells, it was utilized as a
      positive control in these studies. A lactate dehydrogenase (LDH) assay
      demonstrated a moderate cytotoxic effect of the test compounds. Cell cycle
      disturbance and the elevation of the hypodiploid population elicited by the test
      agents were detected by flow cytometry following propidium staining. The
      proapoptotic effects of the tested steroids were confirmed by fluorescent
      microscopy and a caspase-3 activity assay. Treatment-related caspase-9 activation
      without a substantial change in caspase-8 activity indicates the induction of the
      intrinsic apoptotic pathway. The selected agents directly influence the rate of
      tubulin assembly as evidenced by a polymerization assay. Yeast-based reporter
      gene assay revealed that the androgenic activity of the novel 19-nortestosterone
      derivative 3 is by multiple orders of magnitude weaker than that of the reference
      agent 1. Based on the behavior of the examined compounds it can be concluded that
      a halogen substitution of the 19-nortestosterone scaffold at the 17alpha position
      may produce compounds with unique biological activities. The results of the
      present study support that structurally modified steroids with negligible
      hormonal activity are a promising basis for the research and development of novel
      anticancer agents.

PMID- 30100877
TI  - Stationary Atrial Fibrillation Properties in the Goat Do Not Entail Stable or
      Recurrent Conduction Patterns.
AB  - Introduction: Electro-anatomical mapping of the atria is used to identify the
      substrate of atrial fibrillation (AF). Targeting this substrate by ablation in
      addition to pulmonary vein ablation did not consistently improve outcome in
      clinical trials. Generally, the assessment of the substrate is based on short
      recordings (<=10 s, often even shorter). Thus, targeting the AF substrate assumes
      spatiotemporal stationarity but little is known about the variability of
      electrophysiological properties of AF over time. Methods: Atrial fibrillation
      (AF) was maintained for 3-4 weeks after pericardial electrode implantation in 12
      goats. Within a single AF episode 10 consecutive minutes were mapped on the left
      atrial free wall using a 249-electrode array (2.25 mm inter-electrode spacing).
      AF cycle length, fractionation index (FI), lateral dissociation, conduction
      velocity, breakthroughs, and preferentiality of conduction (Pref) were assessed
      per electrode and AF property maps were constructed. The Pearson correlation
      coefficient (PCC) between the 10 AF-property maps was calculated to quantify the
      degree spatiotemporal stationarity of AF properties. Furthermore, the number of
      waves and presence of re-entrant circuits were analyzed in the first 60-s file.
      Comparing conduction patterns over time identified recurrent patterns of AF with
      the use of recurrence plots. Results: The averages of AF property maps were
      highly stable throughout the ten 60-s-recordings. Spatiotemporal stationarity was
      high for all 6 property maps, PCC ranged from 0.66 +/- 0.11 for Pref to 0.98 +/-
      0.01 for FI. High stationarity was lost when AF was interrupted for about 1 h.
      However, the time delay between the recorded files within one episode did not
      affect PCC. Yet, multiple waves (7.7 +/- 2.3) were present simultaneously within
      the recording area and during 9.2 +/- 11% of the analyzed period a re-entrant
      circuit was observed. Recurrent patterns occurred rarely and were observed in
      only 3 out of 12 goats. Conclusions: During non-self-terminating AF in the goat,
      AF properties were stationary. Since this could not be attributed to stable
      recurrent conduction patterns during AF, it is suggested that AF properties are
      determined by anatomical and structural properties of the atria even when the
      conduction patterns are very variable.

PMID- 30100874
TI  - The Pathogenesis of Diabetes Mellitus by Oxidative Stress and Inflammation: Its
      Inhibition by Berberine.
AB  - A substantial knowledge on the pathogenesis of diabetes mellitus (DM) by
      oxidative stress and inflammation is available. Berberine is a biologically
      active botanical that can combat oxidative stress and inflammation and thus
      ameliorate DM, especially type 2 DM. This article describes the potential of
      berberine against oxidative stress and inflammation with special emphasis on its
      mechanistic aspects. In diabetic animal studies, the modified levels of
      proinflammatory cytokines and oxidative stress markers were observed after
      administering berberine. In renal, fat, hepatic, pancreatic and several others
      tissues, berberine-mediated suppression of oxidative stress and inflammation was
      noted. Berberine acted against oxidative stress and inflammation through a very
      complex mechanism consisting of several kinases and signaling pathways involving
      various factors, including NF-kappaB (nuclear factor-kappaB) and AMPK (AMP
      activated protein kinases). Moreover, MAPKs (mitogen-activated protein kinases)
      and Nrf2 (nuclear factor erythroid-2 related factor 2) also have mechanistic
      involvement in oxidative stress and inflammation. In spite of above advancements,
      the mechanistic aspects of the inhibitory role of berberine against oxidative
      stress and inflammation in diabetes mellitus still necessitate additional
      molecular studies. These studies will be useful to examine the new prospects of
      natural moieties against DM.

PMID- 30100879
TI  - Effects of Resting, Consecutive, Long-Duration Water Immersions on Neuromuscular
      Endurance in Well-Trained Males.
AB  - Purpose: This study examined the effects of repeated long-duration water
      immersions (WI)s at 1.35 atmospheres absolute (ATA) on neuromuscular endurance
      performance. We hypothesized that, following 5 days of consecutive, resting, long
      duration WIs, neuromuscular endurance performance would decrease. Methods:
      Fifteen well-trained, male subjects completed five consecutive 6-h resting WIs
      with 18-h surface intervals during the dive week while breathing compressed air
      at 1.35 ATA. Skeletal muscle endurance performance was assessed before and after
      each WI, and 24 and 72 h after the final WI. Muscular endurance assessments
      included 40% maximum handgrip endurance (MHE) and 50-repetition maximal
      isokinetic knee extensions. Near infrared spectroscopy was used to measure muscle
      oxidative capacity of the vastus lateralis and localized muscle tissue
      oxygenation of the vastus lateralis and flexor carpi radialis. Simultaneously,
      brachioradialis neuromuscular activation was measured by surface
      electromyography. Results: A 24.9% increase (p = 0.04) in the muscle oxidative
      capacity rate constant (k) occurred on WI 4 compared to baseline. No changes
      occurred in 40% MHE time to exhaustion or rate of fatigue or total work performed
      for the 50-repetition maximal isokinetic knee extension. The first quartile of
      deoxygenated hemoglobin concentration showed a 6 and 35% increase on WIs 3 and 5
      (p = 0.026) with second quartile increases of 9 and 32% on WIs 3 and 5 (p =
      0.049) during the 40% MHE testing when compared to WI 1. Conclusion: Our specific
      WI protocol resulted in no change to muscular endurance and oxygen kinetics in
      load bearing and non-load bearing muscles.

PMID- 30100878
TI  - Generation and Neuronal Differentiation of hiPSCs From Patients With Myotonic
      Dystrophy Type 2.
AB  - Human induced pluripotent stem cells (hiPSCs)-patient specific are an innovative
      tool to reproduce a model of disease in vitro and summarize the pathological
      phenotype and the disease etiopathology. Myotonic dystrophy type 2 (DM2) is
      caused by an unstable (CCTG)n expansion in intron 1 of the CNBP gene, leading to
      a progressive multisystemic disease with muscle, heart and central nervous
      dysfunctions. The pathogenesis of CNS involvement in DM2 is poorly understood
      since no cellular or animal models fully recapitulate the molecular and clinical
      neurodegenerative phenotype of patients. In this study, we generated for the
      first time, two DM2 and two wild type hiPSC lines from dermal fibroblasts by
      polycistronic lentiviral vector (hSTEMCCA-loxP) expressing OCT4, SOX2, KLF4, and
      cMYC genes and containing loxP-sites, excisable by Cre recombinase. Specific
      morphological, molecular and immunocytochemical markers have confirmed the
      stemness of DM2 and wild type-derived hiPSCs. These cells are able to
      differentiate into neuronal population (NP) expressing tissue specific markers.
      hiPSCs-derived NP cells maintain (CCTG)n repeat expansion and intranuclear RNA
      foci exhibiting sequestration of MBNL1 protein, which are pathognomonic of the
      disease. DM2 hiPSCs represent an important tool for the study of CNS pathogenesis
      in patients, opening new perspectives for the development of cell-based therapies
      in the field of personalized medicine and drug screening.

PMID- 30100880
TI  - Basal Endogenous Steroid Hormones, Sex Hormone-Binding Globulin, Physical
      Fitness, and Health Risk Factors in Young Adult Men.
AB  - Purpose: Few large-scale population-based studies have adequately examined the
      relationships between steroid hormones, health status and physical fitness. The
      purpose of the study was to describe the relationship of serum basal endogenous
      steroid hormones (testosterone, TES; empirical free testosterone, EFT; cortisol,
      COR) and sex hormone-binding globulin (SHBG) to body composition, cardiovascular
      risk factors, and physical fitness in young healthy men. Methods: Male reservists
      (25 +/- 4 years, N = 846) participated in the study. Basal TES, EFT, COR, and
      SHBG were measured in morning fasted blood. Stepwise regression analyses were
      used to examine associations between individual hormones to four separate
      categories: (1) body composition; (2) cardiovascular risk factors; (3) relative,
      and (4) absolute physical fitness. Results: Higher TES, EFT, and SHBG were
      associated with lower waist circumference (TES: beta = -0.239, p < 0.001; EFT:
      beta = -0.385, p < 0.001), % body fat (TES: beta = -0.163, p = 0.003), and body
      mass index (SHBG: beta = -0.435, p < 0.001). Lower cardiovascular risk factors
      were associated with higher TES, EFT and SHBG concentrations, especially between
      SHBG and triglycerides (beta = -0.277, p < 0.001) and HDL (beta = 0.154, p <
      0.001). Greater maximal relative aerobic capacity was concurrent with higher TES,
      EFT, and SHBG (beta = 0.171, 0.113, 0.263, p < 0.001, =0.005, <0.001,
      respectively). Conclusion: Higher basal concentrations of TES, EFT, and SHBG were
      weakly associated with healthier body composition, fewer cardiovascular risk
      factors and greater relative aerobic capacity in healthy young men. It would be
      interesting to investigate whether these relationships are still evident after a
      few decades, and how different training modes (endurance, strength or their
      combination) positively affect physical fitness, body composition and their
      regulatory mechanisms over the decades.

PMID- 30100881
TI  - High-Intensity Interval Training Performed by Young Athletes: A Systematic Review
      and Meta-Analysis.
AB  - Background: High-intensity interval training (HIIT) is as a time-efficient
      alternative to moderate- or low-intensity continuous exercise for improving
      variables related to endurance and anaerobic performance in young and adolescent
      athletes. Objectives: To assess original research about enhancement of endurance
      and anaerobic exercise performance in young and adolescent athletes performing
      HIIT. Method: Relevant articles published in peer-reviewed journals were
      retrieved from the electronic databases PubMed and SPORTDiscus in December 2017.
      Inclusion criteria were: (i) controlled trials (HIIT vs. alternative training
      protocol) with pre-post design; (ii) healthy young athletes (<=18 years); (iii)
      assessing variables related to endurance and exercise performance. Hedges' g
      effect size (ES), and associated 95% confidence intervals were calculated for
      comparison of any outcome between experimental (HIIT) and alternative training
      protocol. Results: Twenty four studies, involving 577 athletes (mean age: 15.5 +/
      2.2 years), were included in this review. HIIT exerted no or small positive mean
      ES on peak oxygen uptake (VO2peak), running performance, repeated sprint ability,
      jumping performance and submaximal heart rate. Although the mean ES for changes
      in VO2peak with HIIT is small (mean g = 0.10+/-0.28), the average increase in
      VO2peak from pre to post HIIT-interventions were 7.2 +/- 6.9% vs. 4.3 +/- 6.9%
      with any other alternative intervention. HIIT largely and positively affected
      running speed and oxygen consumption at various lactate- or ventilatory-based
      thresholds, as well as for sprint running performance. Calculations showed
      negative mean ES for change-of-direction ability (large), and peak blood lactate
      concentrations (small). Mean duration per training session for HIIT was shorter
      than for control interventions (28 +/- 15 min vs. 38 +/- 24 min). Conclusion: The
      present findings suggest that young athletes performing HIIT may improve certain
      important variables related to aerobic, as well as anaerobic, performance. With
      HIIT, most variables related to endurance improved to a higher extent, compared
      to alternative training protocols. However, based on ES, HIIT did not show clear
      superiority to the alternative training protocols. Nevertheless, young athletes
      may benefit from HIIT as it requires less time per training session leaving more
      time for training sport specific skills.

PMID- 30100882
TI  - Dysfunction of Sister Chromatids Separation Promotes Progression of
      Hepatocellular Carcinoma According to Analysis of Gene Expression Profiling.
AB  - Despite studying the various molecular mechanisms of hepatocellular carcinoma
      (HCC), effective drugs and biomarkers in HCC therapy are still scarce. The
      present study was designed to investigate dysregulated pathways, novel biomarkers
      and therapeutic targets for HCC. The gene expression dataset of GSE14520, which
      included 362 tumor and their paired non-tumor tissues of HCC, was extracted for
      processing by the Robust multi-array average (RMA) algorithm in the R
      environment. SAM methods were leveraged to identify differentially expressed
      genes (DEGs). Functional analysis of DEGs was performed using DAVID. The
      GeneMania and Cytohubba were used to construct the PPI network. To avoid
      individual bias, GSEA and survival analysis were employed to verify the results.
      The results of these analyses indicated that separation of sister chromatids was
      the most aberrant phase in the progression of HCC, and the most frequently
      involved genes, EZH2, GINS1, TPX2, CENPF, and BUB1B, require further study to be
      used as drug targets or biomarkers in diagnosis and treatment of HCC.

PMID- 30100883
TI  - Mental Health and Psychosocial Functioning Over the Lifespan of German Patients
      Undergoing Cardiac Catheterization for Coronary Artery Disease.
AB  - Background: Psychological problems are common in patients with coronary artery
      disease (CAD) and are associated with poor outcome. However, data on the
      prevalence of distinct mental disorders and their relevance to patients'
      functioning in daily life are scarce. Method: In this retrospective study, a
      total of 514 German patients with CAD as diagnosed by cardiac catheterization
      were assessed using the Mini International Neuropsychiatric Interview 5.0.0
      (M.I.N.I.) and psychosocial functioning was evaluated using the Global Assessment
      of Functioning (GAF) scale. Results: Twenty-nine percent of the participants
      suffered from at least one mental disorder after the onset of their CAD (mean
      time since onset = 10.86 years, SD = 8.15). In comparison to the period before
      onset of CAD, elevated prevalence rates were found for severe depressive
      episodes, agoraphobia, dysthymia, panic disorder, and hypochondria. Predictors of
      mental disorders after the onset of CAD were female gender, younger age at onset
      of CAD as well as mental disorders and low GAF scores before onset. GAF scores
      decreased after the onset of CAD, recovered only partially, and were influenced
      by mental disorders before onset in women but not in men. Conclusions: Mental
      disorders-especially depression and agoraphobia-are frequent in patients with
      CAD, with women, patients with a younger age at onset of CAD and patients with
      any history of mental disorders especially at risk. Regardless of whether
      patients meet any specific diagnostic criteria, psychosocial functioning is
      markedly impaired after the onset of CAD, underscoring the need for specific
      mental health programs for this patient population. Future research, ideally
      using a prospective design, is necessary to confirm these findings and to further
      the knowledge of prevalence rates of mental disorders and of modifiable risk
      factors for the development of mental disorders in patients with CAD.

PMID- 30100884
TI  - Functional Connectivity Density, Local Brain Spontaneous Activity, and Their
      Coupling Strengths in Patients With Borderline Personality Disorder.
AB  - In this study, combining degree centrality (DC) and fractional amplitude of low
      frequency fluctuation (fALFF) analyses of resting state (rs)-functional magnetic
      resonance imaging (fMRI) data, we aimed to explore functional connectivity
      density, local brain spontaneous activity, and their coupling strengths in
      borderline personality disorder (BPD). Forty-three BPD patients and 39
      demographically-matched controls underwent rs-fMRI after completing a series of
      psychological tests. Two-sample t-tests were performed to compare DC and fALFF
      between these two groups. Across-voxel correlation analysis was conducted to
      assess DC-fALFF coupling strengths in each group. Imaging parameters and
      psychological variables were correlated by Pearson correlation analysis in the
      BPD group. Altered DC and fALFF values in the BPD group, compared with the
      control group, were distributed mainly in default mode network (DMN), and DC
      fALFF coupling strengths were decreased in the left middle temporal gyrus (MTG)
      and right precuneus in the BPD group. Additionally, insecure attachment scores
      correlated positively with left precuneus DC and negatively with fALFF of the
      right posterior cingulate cortex (PCC) in the BPD group. These altered DC and
      fALFF findings indicate that the BPD patients had disturbed functional
      connectivity density and local spontaneous activity in the DMN compared with
      control subjects. Their decreased connectivity-amplitude coupling suggests that
      the left MTG and right precuneus may be functional impairment hubs in BPD.
      Disturbed rs function in the left precuneus and right PCC might underlie insecure
      attachment in BPD.

PMID- 30100885
TI  - Evaluating the Feasibility of a Pilot Exercise Intervention Implemented Within a
      Residential Rehabilitation Unit for People With Severe Mental Illness: GO HEART:
      (Group Occupational Health Exercise and Rehabilitation Treatment).
AB  - Purpose: People with severe mental illness are sedentary, have high cardio
      metabolic risks and significantly reduced life expectancy. Despite considerable
      data regarding positive physical and mental health outcomes following exercise
      interventions, implementation and evaluation of real-world programs is lacking.
      The primary aim of this study was to assess the feasibility of an exercise
      intervention implemented by exercise physiology (EP) students within a
      residential rehabilitation unit for residents with severe mental illness,
      together with assessment of a range of secondary physical and mental health
      outcomes pre- and post- the intervention. Design: Single arm, prospective pilot
      study evaluating outcomes pre- and post- a 10 week intervention. Method: Inactive
      people with severe mental illness participated in a mixed aerobic and resistance
      exercise intervention, three times per week for 10 weeks. Data was obtained from
      a sample of 16 residents with severe mental illness; primary diagnosis
      schizophrenia (n = 12). Primary outcomes were feasibility as assessed using
      recruitment, retention and participation rates, as well as reasons for withdrawal
      and amount of exercise achieved. Secondary outcomes included: functional exercise
      capacity was measured by the 6-min walk test; metabolic data obtained from
      anthropometric measurements; blood pressure; fasting cholesterol and blood sugar
      levels; and physical activity levels and mental health as assessed by self-
      administered questionnaires measured before and after the intervention. Results:
      Broad level acceptance of the program: high recruitment (81%), retention (77%),
      and participation (78%) rates were observed. Promising improvements in functional
      exercise capacity, volume of exercise, and negative symptoms was demonstrated in
      those who completed. Conclusions: Exercise interventions delivered by EP students
      in a residential rehabilitation setting for people with SMI are feasible; group
      setting, supervision and choice for engagement are important considerations.
      Evaluation of longitudinal, multi site studies, with the addition of dietary
      interventions within residential rehabilitation units are warranted. Addressing
      cost feasibility and cost effectiveness of such programs is recommended. The
      trial was registered with the Australian New Zealand Clinical Trials Registry
      (ANZCTR) number, Unique Identifier: ACTRN 12618000478213,
      http://www.anzctr.org.au Universal trial number (UTN) - U1111-1211-4009.

PMID- 30100888
TI  - The Relationship Between Psychological Contract Breach and Employees'
      Counterproductive Work Behaviors: The Mediating Effect of Organizational Cynicism
      and Work Alienation.
AB  - Psychological contract breach (PCB) may trigger negative attitudes in employees
      and ultimately cause further negative behaviors. By drawing on social exchange
      theory, this study aims to explore the link between PCB and counterproductive
      work behavior (CWB) by focusing on the mediating role of organizational cynicism
      and work alienation. We administered a cross-sectional survey of 484 energy
      company front-line employees. The conceptual model was examined via structural
      equation modeling. The results suggested that organizational cynicism and work
      alienation sequentially mediated the relationship between PCB and CWB. This study
      elucidated the mechanisms underlying the relationship between PCB and CWB by
      introducing negative attitudes (i.e., organizational cynicism and work
      alienation) into the model, and offered further evidence that organizations
      should pay more attention to employees' PCB and negative attitudes in order to
      reduce their CWB.

PMID- 30100887
TI  - Neurocognitive Development of the Resolution of Selective Visuo-Spatial
      Attention: Functional MRI Evidence From Object Tracking.
AB  - Our ability to select relevant information from the environment is limited by the
      resolution of attention - i.e., the minimum size of the region that can be
      selected. Neural mechanisms that underlie this limit and its development are not
      yet understood. Functional magnetic resonance imaging (fMRI) was performed during
      an object tracking task in 7- and 11-year-old children, and in young adults.
      Object tracking activated canonical fronto-parietal attention systems and motion
      sensitive area MT in children as young as 7 years. Object tracking performance
      improved with age, together with stronger recruitment of parietal attention areas
      and a shift from low-level to higher-level visual areas. Increasing the required
      resolution of spatial attention - which was implemented by varying the distance
      between target and distractors in the object tracking task - led to activation
      increases in fronto-insular cortex, medial frontal cortex including anterior
      cingulate cortex (ACC) and supplementary motor area, superior colliculi, and
      thalamus. This core circuitry for attentional precision was recruited by all age
      groups, but ACC showed an age-related activation reduction. Our results suggest
      that age-related improvements in selective visual attention and in the resolution
      of attention are characterized by an increased use of more functionally
      specialized brain regions during the course of development.

PMID- 30100889
TI  - Food Advertising Literacy Training Reduces the Importance of Taste in Children's
      Food Decision-Making: A Pilot Study.
AB  - Television food advertising influences children's food choices. The attribute of
      "taste" drives children's food choices, and exposure to food commercials can
      increase the importance of "taste" when children make food decisions. The current
      pilot study explored whether food advertising literacy training influences
      children's food choices. In particular, whether the training would change the way
      children weigh the importance of taste attributes in their food decisions. Thirty
      nine children ages 8-13 were recruited. Twenty-three of those children had four
      sessions of food advertising literacy training (1 week): children watched four
      videos of food commercials embedded with factual narratives (i.e., building
      cognitive defenses; e.g., "commercials want to sell products") and evaluative
      narratives (i.e., changing affective responses toward commercials; e.g., "these
      foods don't make you happy"). The first and last sessions were held in the
      laboratory, and the second and third sessions were at home. During the training,
      children were encouraged to think aloud while watching commercials and provided
      narratives to encourage active information processing. At baseline and post
      training, children made binary eating choices for 60 foods and rated each food
      item on health and taste. We fitted linear regression models to examine whether
      taste and health attributes predicted unique variance in each child's food
      choices. The results showed that taste attributes in children's food choices was
      significantly decreased after completing the training. This finding suggested
      that improving food advertising literacy could be helpful for reducing the
      influence of taste attributes in the food decision-making process. Also, the
      cognitive literacy training increased children's critical thoughts toward
      commercials during thinking aloud. These findings suggest that food advertising
      literacy training was helpful for reducing the importance of "taste" in
      children's food decisions. In contrast, 16 children in the control condition
      (i.e., watching four videos of food commercials without narratives in 1 week) did
      not show any significant change in their food choices. Future research should
      investigate the utility of food advertising literacy training for the promotion
      of healthy eating and the prevention of childhood obesity.

PMID- 30100886
TI  - Resting State Functional Connectivity of the Lateral and Medial Hypothalamus in
      Cocaine Dependence: An Exploratory Study.
AB  - The role of dopamine in cocaine misuse has been extensively documented for the
      mesocorticolimbic circuit. Preclinical work from earlier lesion studies to recent
      multidisciplinary investigations has suggested that the hypothalamus is
      critically involved in motivated behavior, with the lateral and medial
      hypothalamus each involved in waking/feeding and resting/satiety. However, little
      is known of hypothalamus function and dysfunction in cocaine misuse. Here, we
      examined resting state functional connectivity of the lateral and medial
      hypothalamus in 70 individuals with cocaine dependence (CD) and 70 age as well as
      gender matched healthy controls (HC). Image pre-processing and analyses followed
      published work. Compared to HC, CD showed increased lateral hypothalamic
      connectivity with dorsolateral prefrontal cortex and decreased functional
      connectivity with the ventral precuneus. CD showed increased medial hypothalamic
      connectivity with the inferior parietal lobule and decreased connectivity with
      the ventromedial prefrontal cortex, temporal gyrus, fusiform gyrus, and ventral
      striatum. Further, at trend level significance, the connectivity strength between
      lateral hypothalamus and dorsolateral prefrontal cortex was positively correlated
      with total amount of cocaine use in the past month (p = 0.004, r = 0.35) and the
      connectivity strength between medial hypothalamus and ventral striatum was
      negatively correlated with cocaine craving as assessed by the Tiffany Cocaine
      Craving Questionnaire (p = 0.008, r = -0.33). Together, the findings demonstrated
      altered resting state functional connectivity of the hypothalamus and may provide
      new insight on circuit level deficits in cocaine dependence.

PMID- 30100891
TI  - Applying Logistic Regression to Detect Differential Item Functioning in
      Multidimensional Data.
AB  - Conventional differential item functioning (DIF) approaches such as logistic
      regression (LR) often assume unidimensionality of a scale and match participants
      in the reference and focal groups based on total scores. However, many
      educational and psychological assessments are multidimensional by design, and a
      matching variable using total scores that does not reflect the test structure may
      not be good practice in multidimensional items for DIF detection. We propose the
      use of all subscores of a scale in LR and compare its performance with
      alternative matching methods, including the use of total score and individual
      subscores. We focused on uniform DIF situation in which 250, 500, or 1,000
      participants in each group answered 21 items reflecting two dimensions, and the
      21st item was the studied item. Five factors were manipulated in the study: (a)
      the test structure, (b) numbers of cross-loaded items, (c) group differences in
      latent abilities, (d) the magnitude of DIF, and (e) group sample size. The
      results showed that, when the studied item measured a single domain, the
      conventional LR incorporating total scores as a matching variable yielded
      inflated false positive rates (FPRs) when two groups differed in one latent
      ability. The situation worsened when one group had a higher ability in one domain
      and lower ability in another. The LR using a single subscore as the matching
      variable performed well in terms of FPRs and true positive rates (TPRs) when two
      groups did not differ in either one latent ability or differed in one latent
      ability. However, this approach yielded inflated FPRs when two groups differed in
      two latent abilities. The proposed LR using two subscores yielded well-controlled
      FPRs across all conditions and yielded the highest TPRs. When the studied item
      measured two domains, the use of either the total score or two subscores worked
      well in the control of FPRs and yielded similar TPRs across conditions, whereas
      the use of a single subscore resulted in inflated FPRs when two groups differed
      in one or two latent abilities. In conclusion, we recommend the use of multiple
      subscores to match subjects in DIF detection for multidimensional data.

PMID- 30100890
TI  - The Way We Do the Things We Do: How Cognitive Contexts Shape the Neural Dynamics
      of Motor Areas in Humans.
AB  - In spontaneously triggered movements the nature of the executed response has a
      prominent effect on the intensity and the dynamics of motor areas recruitment.
      Under time pressure, the time course of motor areas recruitment is necessarily
      shorter than that of spontaneously triggered movements because RTs may be
      extremely short. Moreover, different classes of RT tasks allow examining the
      nature and the dynamics of motor areas activation in different cognitive
      contexts. In the present article, we review experimental results obtained from
      high temporal resolution methods (mainly, but not exclusively EEG ones), during
      voluntary movements; these results indicate that the activity of motor areas not
      only depends on the nature of the executed movement but also on the cognitive
      context in which these movements have to be executed.

PMID- 30100892
TI  - Is It Me or You?-How Reactions to Abusive Supervision Are Shaped by Leader
      Behavior and Follower Perceptions.
AB  - There is a growing interest in understanding how follower reactions toward
      abusive leadership are shaped by followers' perceptions and attributions. Our
      studies add to the understanding of the process happening between different
      levels of leaders' abusive behavior (from constructive leadership as control,
      laissez-faire, mild to strong abusive) and follower reactions. Specifically, we
      focus on the role of perception of abusive supervision as a mediator and
      attribution as a moderator of the relationship between leader abusive behavior
      and follower reactions. Follower reactions are defined in terms of exit, voice,
      loyalty, and neglect. Two studies using a two point experimental design and
      vignettes and a cross-sectional field study were conducted. Perception partly
      mediates the relationship between leader behavior and reactions (Study 1 and 2).
      Different attributions (intention, control) moderate the relationship between the
      perception of abusive supervision and reactions in Study 2 and 3. In Study 2,
      attribution of intentionality of the leader behavior served as a moderator of the
      relationship between abusive supervision and loyalty, turnover, and voice.
      Attribution of intentionality reduced the relationship between perception of
      abusive supervision and reactions. Attribution of intentionality only
      strengthened negative reactions when milder abusive leadership was perceived.
      These results were not supported in Study 3. However, in Study 3, attribution to
      the supervisor' control served as moderator for loyalty and voice. A stronger
      relationship between the perception of abusive supervision and reactions emerged
      for high vs. for low attribution to the supervisor. The differences in results
      between the studies reflect that in Study 1 and 2 abusive behavior was
      manipulated and in Study 3 the perception of abusive supervision of actual
      leaders was assessed. Our findings show that avoidance of abusive supervision
      should be taken seriously and followers' perception and suffering is not only due
      to subjective judgment but reflects actual differences in behavior. The
      relationships are stronger in the field study, because, in practice, abusive
      behaviors might be more ambiguous. The research presented here can help leaders
      to better understand their own and the followers' role in the perception of and
      reaction to abusive supervision.

PMID- 30100893
TI  - Do Exact Calculation and Computation Estimation Reflect the Same Skills?
      Developmental and Individual Differences Perspectives.
AB  - Groups of children in 4th, 5th, and 6th grades and college students performed
      exact calculation and computation estimation tasks with two-digit multiplication
      problems. In the former they calculated the exact answer for each problem, and in
      the latter they estimated whether the result of each problem was larger or
      smaller than a given reference number. The analyses of speed and accuracy both
      showed different developmental patterns of the two tasks. While the accuracy of
      exact calculation increased with age in childhood, the accuracy of the estimation
      task reached its maximum level already in 4th grade and did not change with age.
      The reaction time of the exact calculation task was longer than that of the
      estimation task. The reaction time for both tasks remained constant in childhood
      and decreased in adulthood, with the improvement in speed larger for the exact
      calculation task. Similarly, within group variability in accuracy was larger in
      the exact calculation task than in the computation estimation task. Finally, low
      correlation was found between the accuracy of the two tasks. Together, these
      findings suggest that exact calculation and computation estimation reflect at
      least in part different skills.

PMID- 30100894
TI  - The Rapid Forgetting of Faces.
AB  - How are faces forgotten? Studies examining forgetting in visual working memory
      (VWM) typically use simple visual features; however, in ecological scenarios, VWM
      typically contains complex objects. Given their significance in everyday
      functioning and their visual complexity, here we investigated how upright and
      inverted faces are forgotten within a few seconds, focusing on the raw errors
      that accompany such forgetting and examining their characteristics. In three
      experiments we found that longer retention intervals increased the size of
      errors. This effect was mainly accounted for by a larger proportion of random
      errors - suggesting that forgetting of faces reflects decreased accessibility of
      the memory representations over time. On the other hand, longer retention
      intervals did not modulate the precision of recall - suggesting that forgetting
      does not affect the precision of accessible memory representation. Thus, when
      upright and inverted faces are forgotten there is a complete failure to access
      them or a complete collapse of their memory representation. In contrast to the
      effect of retention interval (i.e., forgetting), face inversion led to larger
      errors that were mainly associated with decreased precision of recall. This
      effect was not modulated by the duration of the retention interval, and was
      observed even when memory was not required in the task. Therefore, upright faces
      are remembered more precisely compared to inverted ones due to perceptual, rather
      than mnemonic processes.

PMID- 30100895
TI  - Gender Trouble in Social Psychology: How Can Butler's Work Inform Experimental
      Social Psychologists' Conceptualization of Gender?
AB  - A quarter of a century ago, philosopher Judith Butler (1990) called upon society
      to create "gender trouble" by disrupting the binary view of sex, gender, and
      sexuality. She argued that gender, rather than being an essential quality
      following from biological sex, or an inherent identity, is an act which grows out
      of, reinforces, and is reinforced by, societal norms and creates the illusion of
      binary sex. Despite the fact that Butler's philosophical approach to
      understanding gender has many resonances with a large body of gender research
      being conducted by social psychologists, little theorizing and research within
      experimental social psychology has drawn directly on Butler's ideas. In this
      paper, we will discuss how Butler's ideas can add to experimental social
      psychologists' understanding of gender. We describe the Butler's ideas from
      Gender Trouble and discuss the ways in which they fit with current
      conceptualizations of gender in experimental social psychology. We then propose a
      series of new research questions that arise from this integration of Butler's
      work and the social psychological literature. Finally, we suggest a number of
      concrete ways in which experimental social psychologists can incorporate notions
      of gender performativity and gender trouble into the ways in which they research
      gender.

PMID- 30100897
TI  - Insights Into Sexual Maturation and Reproduction in the Norway Lobster (Nephrops
      norvegicus) via in silico Prediction and Characterization of Neuropeptides and G
      Protein-coupled Receptors.
AB  - Multiple biological processes across development and reproduction are modulated
      by neuropeptides that are predominantly produced and secreted from an animal's
      central nervous system. In the past few years, advancement of next-generation
      sequencing technologies has enabled large-scale prediction of putative
      neuropeptide genes in multiple non-model species, including commercially
      important decapod crustaceans. In contrast, knowledge of the G protein-coupled
      receptors (GPCRs), through which neuropeptides act on target cells, is still very
      limited. In the current study, we have used in silico transcriptome analysis to
      elucidate genes encoding neuropeptides and GPCRs in the Norway lobster (Nephrops
      norvegicus), which is one of the most valuable crustaceans in Europe. Fifty-seven
      neuropeptide precursor-encoding transcripts were detected, including phoenixin, a
      vertebrate neurohormone that has not been detected in any invertebrate species
      prior to this study. Neuropeptide gene expression analysis of immature and mature
      female N. norvegicus, revealed that some reproduction-related neuropeptides are
      almost exclusively expressed in immature females. In addition, a total of 223
      GPCR-encoding transcripts were identified, of which 116 encode GPCR-A
      (Rhodopsin), 44 encode GPCR-B (Secretin) and 63 encode other GPCRs. Our findings
      increase the molecular toolbox of neural signaling components in N. norvegicus,
      allowing for further advances in the fisheries/larvae culture of this species.

PMID- 30100898
TI  - Selection of Pof-Saccharomyces eubayanus Variants for the Construction of S.
      cerevisiae * S. eubayanus Hybrids With Reduced 4-Vinyl Guaiacol Formation.
AB  - Saccharomyces pastorianus is an interspecies hybrid between S. cerevisiae and S.
      eubayanus. The identification of the parental species of S. pastorianus enabled
      the de novo reconstruction of hybrids that could potentially combine a wide array
      of phenotypic traits. Lager yeasts are characterized by their inability to
      decarboxylate ferulic acid present in wort, a phenotype also known as Pof -
      (phenolic off-flavor). However, all known S. eubayanus strains characterized so
      far produce clove-like aroma specific of 4-vinyl guaiacol, a decarboxylated form
      of ferulic acid. This study explored a non-GMO approach to construct Pof -S.
      eubayanus variants derived from the parental strain S. eubayanus CBS 12357. To
      rapidly screen a population of UV-mutagenized cells two complementary assays were
      developed. The first assay was based on the difference of light absorption
      spectra of ferulic acid and 4-vinyl guaiacol, while the second was based on the
      difference of sensitivity of Pof - and Pof+ strains to cinnamic acid. The S.
      eubayanus variant HTSE042 was selected and was confirmed not to produce 4-vinyl
      guaiacol. Whole genome sequencing revealed that this variant lost the
      subtelomeric region of the CHRXIII right arm that carried the two clustered genes
      SePAD1- SeFDC1 whose deletion in a naive S. eubayanus strain (CBS 12357/FM1318)
      resulted in an identical phenotype. Subsequently, the Pof - variant was crossed
      with a Pof-S. cerevisiae partner. The resulting hybrid was not able to convert
      ferulic acid demonstrating the undisputable value of the mutagenized variant
      HTSE042 to eventually construct S. cerevisiae * S. eubayanus hybrids with
      phenotypic characteristics of S. pastorianus.

PMID- 30100899
TI  - Metabolic Engineering of Escherichia coli for Enhanced Production of Naringenin 7
      Sulfate and Its Biological Activities.
AB  - Flavonoids are one of the predominant groups of plant polyphenols, and these
      compounds have significant effects on human health and nutrition. Sulfated
      flavonoids have more favorable attributes compared to their parent compounds such
      as increased solubility, stability, and bioavailability. In this research, we
      developed a microbial system to produce sulfated naringenin using Escherichia
      coli expressing a sulfotransferase (ST) from Arabidopsis thaliana (At2g03770).
      This wild-type strain was used as a model system for testing clustered regularly
      interspaced short palindromic repeats (CRISPR) interference (CRISPRi) metabolic
      engineering strategies. Using synthetic sgRNA to mediate transcriptional
      repression of cysH, a gene encoding 3'-phosphoadenosine-5'-phosphosulfate (PAPS)
      ST, which is involved in sulfur metabolism, resulted in an increase in
      intracellular PAPS accumulation by over 3.28-fold without impairing cell growth.
      Moreover, naringenin 7-sulfate production by engineering E. coli with its cysH
      gene repressed in the open reading frame through CRISPRi was enhanced by 2.83
      fold in compared with the wild-type control. To improve the efficiency of
      biotransformation, the concentration of SO42- , glucose, and substrate were
      optimized. The bioproductivity of naringenin 7-sulfate was 135.49 MUM [~143.1 mg
      (47.7 mg L-1)] in a 3-L fermenter at 36 h. These results demonstrated that the
      CRISPRi system was successfully applied for the first time in E. coli to develop
      an efficient microbial strain for production of a sulfated flavonoid. In
      addition, antibacterial and anticancer activities of naringenin 7-sulfate were
      investigated and found to be higher than the parent compound.

PMID- 30100896
TI  - Communication Matters-Pitfalls and Promise of Hightech Communication Devices in
      Palliative Care of Severely Physically Disabled Patients With Amyotrophic Lateral
      Sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common motor neuron disease,
      leading to progressive paralysis, dysarthria, dysphagia, and respiratory
      disabilities. Therapy is mostly focused on palliative interventions. During the
      course of the disease, verbal as well as nonverbal communicative abilities become
      more and more impaired. In this light, communication has been argued to be "the
      essence of human life" and crucial for patients' quality of life. High-tech
      augmentative and alternative communication (HT-AAC) technologies such as
      eyetracking based computer devices and brain-computer-interfaces provide the
      possibility to maintain caregiver-independent communication and environmental
      control even in the advanced disease state of ALS. Thus, they enable patients to
      preserve social participation and to independently communicate end-of-life
      decisions. In accordance with these functions of HT-AAC, their use is reported to
      strengthen self-determination, increase patients' quality of life and reduce
      caregiver burden. Therefore, HT-AAC should be considered as standard of
      (palliative) care for people with ALS. On the other hand, the supply with
      individually tailored HT-AAC technologies is limited by external and patient
      inherent variables. This review aims to provide an overview of the possibilities
      and limitations of HT-AAC technologies and discuss their role in the palliative
      care for patients with ALS.

PMID- 30100900
TI  - Quantitative Proteomics Analysis of Membrane Proteins in Enterococcus faecalis
      With Low-Level Linezolid-Resistance.
AB  - Despite increasing reports of low-level linezolid-resistant enterococci
      worldwide, the mechanism of this resistance remains poorly understood. Previous
      transcriptome studies of low-level linezolid-resistant Enterococcus faecalis
      isolates have demonstrated a number of significantly up-regulated genes
      potentially involved in mediation of drug resistance. However, whether the
      transcriptome faithfully reflects the proteome remains unknown. In this study, we
      performed quantitative proteomics analysis of membrane proteins in an E. faecalis
      isolate (P10748) with low-level linezolid-resistance in comparison with two
      linezolid-susceptible strains 3138 and ATCC 29212, all of which have been
      previously investigated by whole transcriptome analysis. A total of 8,197
      peptides associated with 1,170 proteins were identified in all three isolates
      with false discovery rate (FDR) at 1% and P < 0.05. There were 14 significantly
      up-regulated and 6 significantly down-regulated proteins in strain P10748
      compared to strains 3138 and ATCC 29212, which were in general positively
      correlated with transcription levels revealed in previous transcriptome studies.
      Our analysis suggests that the low-level linezolid-resistance in E. faecalis is
      conferred primarily by the ATP-binding cassette protein OptrA through ribosomal
      protection and, possibly, also by the enterococcal surface protein (Esp) and
      other proteins through biofilm formation. The genetic transfer of optrA is
      potentially regulated by the surface exclusion protein Sea1, conjugal transfer
      protein TraB, replication protein RepA and XRE family transcription regulator
      protein. This report represents the first investigation of the mechanisms of
      linezolid-resistance in E. faecalis by a quantitative proteomics approach.

PMID- 30100901
TI  - Prevalence, Potential Virulence, and Genetic Diversity of Listeria monocytogenes
      Isolates From Edible Mushrooms in Chinese Markets.
AB  - Listeria monocytogenes, an intracellular foodborne pathogen, is capable of
      causing listeriosis, such as meningitis, meningoencephalitis, and abortion. In
      recent years, the occurrence of Listeria monocytogenes in edible mushroom
      products has been reported in several countries. There are no guidelines for
      qualitative and quantitative detection of L. monocytogenes in mushroom products
      in China. Therefore, this study aimed to investigate the prevalence and
      contamination level of L. monocytogenes in edible mushrooms in Chinese markets
      and to determine the antibiotic resistance and sequence types (STs) of these
      isolates to provide data for risk assessments. Approximately 21.20% (141/665) of
      edible mushroom samples were positive for L. monocytogenes, while 57.44% (81/141)
      of positive samples contained contamination levels of less than 10 MPN/g. The 180
      isolates derived from positive samples belonged to serogroup I.1 (1/2a-3a, n =
      111), followed by serogroup II.2 (1/2b-3b-7, n = 66), and serogroup III (4a-4c, n
      = 3). Antibiotic susceptibility testing showed that over 95% of L. monocytogenes
      isolates were resistant to penicillin, ampicillin, oxacillin, and clindamycin,
      while over 90% were susceptible to 16 antibiotic agents, the mechanisms of
      resistance remain to be elucidated. According to multilocus sequencing typing,
      the 180 isolates represented 21 STs, one of which was identified for the first
      time. Interestingly, ST8 and ST87 were predominant in edible mushroom products,
      indicating that specific STs may have distinct ecological niches. Potential
      virulence profiles showed that most of the isolates contained full-length inlA
      genes, with novel premature stop codons found in isolate 2035-1LM (position 1380,
      TGG->TGA) and 3419-1LM (position 1474, CAG->TAG). Five isolates belonging to
      serogroup II.2 carried the llsX gene from Listeria pathogenicity island (LIPI)-3,
      present in ST224, ST3, and ST619; 53 (29.44%) harbored the ptsA gene from LIPI-4,
      presenting in ST3, ST5, ST87, ST310, ST1166, and ST619. Five potential
      hypervirulent isolates carrying all three of these virulence factors were
      identified, suggesting edible mushrooms may serve as possible transmission routes
      of potential hypervirulent L. monocytogenes, which may be of great public health
      concern to consumers. Based on our findings, the exploration of novel approaches
      to control L. monocytogenes contamination is necessary to ensure the
      microbiological safety of edible mushroom products.

PMID- 30100902
TI  - Innate Immunity Induced by the Major Allergen Alt a 1 From the Fungus Alternaria
      Is Dependent Upon Toll-Like Receptors 2/4 in Human Lung Epithelial Cells.
AB  - Allergens are molecules that elicit a hypersensitive inflammatory response in
      sensitized individuals and are derived from a variety of sources. Alt a 1 is the
      most clinically important secreted allergen of the ubiquitous fungus, Alternaria.
      It has been shown to be a major allergen causing IgE-mediated allergic response
      in the vast majority of Alternaria-sensitized individuals. However, no studies
      have been conducted in regards to the innate immune eliciting activities of this
      clinically relevant protein. In this study, recombinant Alt a 1 was produced,
      purified, labeled, and incubated with BEAS-2B, NHBE, and DHBE human lung
      epithelial cells. Alt a 1 elicited strong induction of IL-8, MCP-1, and Gro
      a/b/g. Using gene-specific siRNAs, blocking antibodies, and chemical inhibitors
      such as LPS-RS, it was determined that Alt a 1-induced immune responses were
      dependent upon toll-like receptors (TLRs) 2 and 4, and the adaptor proteins MYD88
      and TIRAP. Studies utilizing human embryonic kidney cells engineered to express
      single receptors on the cell surface such as TLRs, further confirmed that Alt a 1
      induced innate immunity is dependent upon TLR4 and to a lesser extent TLR2.

PMID- 30100903
TI  - Host-Derived Microvesicles Carrying Bacterial Pore-Forming Toxins Deliver Signals
      to Macrophages: A Novel Mechanism of Shaping Immune Responses.
AB  - Bacterial infectious diseases are a leading cause of death. Pore-forming toxins
      (PFTs) are important virulence factors of Gram-positive pathogens, which disrupt
      the plasma membrane of host cells and can lead to cell death. Yet, host defense
      and cell membrane repair mechanisms have been identified: i.e., PFTs can be
      eliminated from membranes as microvesicles, thus limiting the extent of cell
      damage. Released into an inflammatory environment, these host-derived PFTs
      carrying microvesicles encounter innate immune cells as first-line defenders.
      This study investigated the impact of microvesicle- or liposome-sequestered PFTs
      on human macrophage polarization in vitro. We show that microvesicle-sequestered
      PFTs are phagocytosed by macrophages and induce their polarization into a novel
      CD14+MHCIIlowCD86low phenotype. Macrophages polarized in this way exhibit an
      enhanced response to Gram-positive bacterial ligands and a blunted response to
      Gram-negative ligands. Liposomes, which were recently shown to sequester PFTs and
      so protect mice from lethal bacterial infections, show the same effect on
      macrophage polarization in analogy to host-derived microvesicles. This novel type
      of polarized macrophage exhibits an enhanced response to Gram-positive bacterial
      ligands. The specific recognition of their cargo might be of advantage in the
      efficiency of targeted bacterial clearance.

PMID- 30100904
TI  - iBCE-EL: A New Ensemble Learning Framework for Improved Linear B-Cell Epitope
      Prediction.
AB  - Identification of B-cell epitopes (BCEs) is a fundamental step for epitope-based
      vaccine development, antibody production, and disease prevention and diagnosis.
      Due to the avalanche of protein sequence data discovered in postgenomic age, it
      is essential to develop an automated computational method to enable fast and
      accurate identification of novel BCEs within vast number of candidate proteins
      and peptides. Although several computational methods have been developed, their
      accuracy is unreliable. Thus, developing a reliable model with significant
      prediction improvements is highly desirable. In this study, we first constructed
      a non-redundant data set of 5,550 experimentally validated BCEs and 6,893 non
      BCEs from the Immune Epitope Database. We then developed a novel ensemble
      learning framework for improved linear BCE predictor called iBCE-EL, a fusion of
      two independent predictors, namely, extremely randomized tree (ERT) and gradient
      boosting (GB) classifiers, which, respectively, uses a combination of
      physicochemical properties (PCP) and amino acid composition and a combination of
      dipeptide and PCP as input features. Cross-validation analysis on a benchmarking
      data set showed that iBCE-EL performed better than individual classifiers (ERT
      and GB), with a Matthews correlation coefficient (MCC) of 0.454. Furthermore, we
      evaluated the performance of iBCE-EL on the independent data set. Results show
      that iBCE-EL significantly outperformed the state-of-the-art method with an MCC
      of 0.463. To the best of our knowledge, iBCE-EL is the first ensemble method for
      linear BCEs prediction. iBCE-EL was implemented in a web-based platform, which is
      available at http://thegleelab.org/iBCE-EL. iBCE-EL contains two prediction
      modes. The first one identifying peptide sequences as BCEs or non-BCEs, while
      later one is aimed at providing users with the option of mining potential BCEs
      from protein sequences.

PMID- 30100905
TI  - Glycogen Metabolism and Rheumatoid Arthritis: The Role of Glycogen Synthase 1 in
      Regulation of Synovial Inflammation via Blocking AMP-Activated Protein Kinase
      Activation.
AB  - Objective: To investigate the role of glycogen metabolism in regulating
      rheumatoid fibroblast-like synoviocyte (FLS)-mediated synovial inflammation and
      its underlying mechanism. Methods: FLSs were separated from synovial tissues
      (STs) obtained from rheumatoid arthritis (RA) patients. Glycogen content was
      determined by periodic acid Schiff staining. Protein expression was analyzed by
      Western blot or immunohistochemistry. Gene expression of cytokines and matrix
      metalloproteinases (MMPs) was evaluated by quantitative real-time PCR. FLS
      proliferation was detected by EdU incorporation. Migration and invasion were
      measured by Boyden chamber assay. Results: Glycogen levels and glycogen synthase
      1 (GYS1) expression were significantly increased in the ST and FLSs of RA
      patients. TNF-alpha or hypoxia induced GYS1 expression and glycogen synthesis in
      RA FLSs. GYS1 knockdown by shRNA decreased the expression of IL-1beta, IL-6, CCL
      2, MMP-1, and MMP-9 and proliferation and migration by increasing AMP-activated
      protein kinase (AMPK) activity in RA FLS. AMPK inhibitor or knockdown AMPK could
      reverse the inhibitory effect of GYS1 knockdown on the inflammatory response in
      RA FLSs; however, an AMPK agonist blocked RA FLS activity. We further determined
      that hypoxia-inducible factor-1alpha mediates TNF-alpha- or hypoxia-induced GYS1
      expression and glycogen levels. Local joint depletion of GYS1 or intraperitoneal
      administration with an AMPK agonist ameliorated the severity of arthritis in rats
      with collagen-induced arthritis. Conclusion: Our data demonstrate that GYS1
      mediated glycogen accumulation contributes to FLS-mediated synovial inflammation
      in RA by blocking AMPK activation. In our knowledge, this is a first study
      linking glycogen metabolism to chronic inflammation. Inhibition of GYS1 might be
      a novel therapeutic strategy for chronic inflammatory arthritis, including RA.

PMID- 30100906
TI  - Targeting Resident Memory T Cells for Cancer Immunotherapy.
AB  - A novel population of memory CD8+ T cells called resident memory T cells (TRM)
      has been identified based on their phenotype (CD103, CD69) and on their local
      tissue residency without recirculating in the blood. These cells have been
      implicated in protective immune response against pathogens in both animal models
      and humans. Their role in cancer is just emerging as a key player in tumor
      immunosurveillance. Many properties of these cells suggest that they could
      control tumor growth: (i) they respond much faster to reexposure to cognate
      antigen than circulating memory cells, (ii) they express high levels of cytotoxic
      molecules, and (iii) they are enriched in tumor-specific T cells in close contact
      with tumor cells. TRM are present in many human cancers and are associated with a
      good clinical outcome independently of the infiltration of CD8+ T cells. It has
      been recently shown that the efficacy of cancer vaccines depends on their ability
      to elicit TRM. In adoptive cell therapy, the transfer of cells with the ability
      to establish TRM at the tumor site correlates with the potency of this approach.
      Interestingly, TRM express immune checkpoint molecules and preliminary data
      showed that they could expand early during anti-PD-1 treatment, and thus be
      considered as a surrogate marker of response to immunotherapy. Some cues to
      better expand these cells in vivo and improve the success of cancer immunotherapy
      include using mucosal routes of immunization, targeting subpopulations of
      dendritic cells as well as local signal at the mucosal site to recruit them in
      mucosal tissue.

PMID- 30100907
TI  - Oral Versus Intragastric Inoculation: Similar Pathways of Trypanosoma cruzi
      Experimental Infection? From Target Tissues, Parasite Evasion, and Immune
      Response.
AB  - Currently, oral infection is the most frequent transmission mechanism of Chagas
      disease in Brazil and others Latin American countries. This transmission pathway
      presents increased mortality rate in the first 2 weeks, which is higher than the
      calculated mortality after the biting of infected insect vectors. Thus, the oral
      route of Trypanosoma cruzi infection, and the consequences in the host must be
      taken into account when thinking on the mechanisms underlying the natural history
      of the disease. Distinct routes of parasite entry may differentially affect
      immune circuits, stimulating regional immune responses that impact on the overall
      profile of the host protective immunity. Experimental studies related to oral
      infection usually comprise inoculation in the mouth (oral infection, OI) or
      gavage (gastrointestinal infection, GI), being often considered as similar routes
      of infection. Hence, establishing a relationship between the inoculation site (OI
      or GI) with disease progression and the mounting of T. cruzi-specific regional
      immune responses is an important issue to be considered. Here, we provide a
      discussion on studies performed in OI and GI in experimental models of acute
      infections, including T. cruzi infection.

PMID- 30100908
TI  - beta-Defensin 1 Is Prominent in the Liver and Induced During Cholestasis by
      Bilirubin and Bile Acids via Farnesoid X Receptor and Constitutive Androstane
      Receptor.
AB  - Background & aims: Knowledge about innate antimicrobial defense of the liver is
      limited. We investigated hepatic expression and regulation of antimicrobial
      peptides with focus on the human beta defensin-1 (hBD-1). Methods: Radial
      diffusion assay was used to analyze antimicrobial activity of liver tissue.
      Different defensins including hBD-1 and its activator thioredoxin-1 (TXN) were
      analyzed in healthy and cholestatic liver samples by qPCR and immunostaining.
      Regulation of hBD-1 expression was studied in vitro and in vivo using bile duct
      ligated mice. Regulation of hBD-1 via bilirubin and bile acids (BAs) was studied
      using siRNA. Results: We found strong antimicrobial activity of liver tissue
      against Escherichia coli. As a potential mediator of this antimicrobial activity
      we detected high expression of hBD-1 and TXN in hepatocytes, whereas other
      defensins were minimally expressed. Using a specific antibody for the reduced,
      antimicrobially active form of hBD-1 we found hBD-1 in co-localization with TXN
      within hepatocytes. hBD-1 was upregulated in cholestasis in a graded fashion. In
      cholestatic mice hepatic AMP expression (Defb-1 and Hamp) was enhanced. Bilirubin
      and BAs were able to induce hBD-1 in hepatic cell cultures in vitro. Treatment
      with siRNA and/or agonists demonstrated that the farnesoid X receptor (FXR)
      mediates basal expression of hBD-1, whereas both constitutive androstane receptor
      (CAR) and FXR seem to be responsible for the induction of hBD-1 by bilirubin.
      Conclusion: hBD-1 is prominently expressed in hepatocytes. It is induced during
      cholestasis through bilirubin and BAs, mediated by CAR and especially FXR.
      Reduction by TXN activates hBD-1 to a potential key player in innate
      antimicrobial defense of the liver.

PMID- 30100910
TI  - Human Plasmablast Migration Toward CXCL12 Requires Glucose Oxidation by Enhanced
      Pyruvate Dehydrogenase Activity via AKT.
AB  - Migration of human plasmablast to the bone marrow is essential for the final
      differentiation of plasma cells and maintenance of effective humoral immunity.
      This migration is controlled by CXCL12/CXCR4-mediated activation of the protein
      kinase AKT. Herein, we show that the CXCL12-induced migration of human
      plasmablasts is dependent on glucose oxidation. Glucose depletion markedly
      inhibited plasmablast migration by 67%, and the glucose analog 2-deoxyglucose (2
      DG) reduced the migration by 53%; conversely, glutamine depletion did not reduce
      the migration. CXCL12 boosted the oxygen consumption rate (OCR), and 2-DG
      treatment significantly reduced the levels of all measured tricarboxylic acid
      (TCA) cycle intermediates. AKT inhibitors blocked the CXCL12-mediated increase of
      OCR. CXCL12 enhanced the pyruvate dehydrogenase (PDH) activity by 13.5-fold in an
      AKT-dependent manner to promote mitochondrial oxidative phosphorylation. The
      knockdown and inhibition of PDH confirmed its indispensable role in CXCL12
      induced migration. Cellular ATP levels fell by 91% upon exposure to 2-DG, and the
      mitochondrial ATP synthase inhibitor oligomycin inhibited CXCL12-induced
      migration by 85%. Low ATP levels inhibited the CXCL12-induced activation of AKT
      and phosphorylation of myosin light chains by 42%, which are required for cell
      migration. Thus, we have identified a mechanism that controls glucose oxidation
      via AKT signaling and PDH activation, which supports the migration of
      plasmablasts. This mechanism can provide insights into the proper development of
      long-lived plasma cells and is, therefore, essential for optimal humoral
      immunity. To our knowledge, this study is the first to investigate metabolic
      mechanisms underlying human plasmablast migration toward CXCL12.

PMID- 30100911
TI  - Evaluation of Gelatin as a Biostimulant Seed Treatment to Improve Plant
      Performance.
AB  - The effect of gelatin, used as a biostimulant, was investigated on plant growth
      in greenhouse studies. Biostimulants are materials that stimulate plant growth,
      and gelatin, an animal protein hydrolysate, is classified as one type of
      biostimulant. Gelatin has a unique amino acid composition with a high percentage
      of proline and hydroxyproline. In a series of experiments gelatin capsules (#3
      hard gelatin) containing 7.1 mg nitrogen each, were placed adjacent to seeds of
      different crop species, at sowing time in individual growing containers and
      several growth parameters were measured. Different types of hydrolyzed collagen,
      including granulated gelatin, gelatin hydrolysate, and amino acid mixtures
      simulating the composition of gelatin were compared on cucumber plant growth. In
      addition, amino acid mixtures without proline, hydroxyproline, or applied in
      combination were investigated on cucumber growth. All capsule treatments
      significantly enhanced crop growth compared to the non-treated control. The
      treatment with two gelatin capsules placed adjacent to each seed increased shoot
      dry weight of cucumber, pepper, broccoli, tomato, arugula, and field corn, by
      138, 244, 50, 45, 41, and 18 percent, respectively. In an experiment with
      cucumber alone, there was a positive linear relationship between the number of
      gelatin capsules from 0 to 3 capsules on plant growth and plant nitrogen content.
      Cucumber growth and plant nitrogen content was greater from the hydrolyzed
      collagen treatment compared with the low molecular weight gelatin hydrolysate, a
      mixture of amino acids or urea and all treatments provided an equivalent amount
      of nitrogen. Proline and/or hydroxyproline were not responsible for the
      biostimulant effect. In summary, gelatin provided nitrogen that enhanced plant
      growth. Moreover, gelatin was an effective biostimulant as the plant growth and
      nitrogen content was greater from two gelatin capsules compared to amino acid
      mixture of the same proportion and amount as the gelatin.

PMID- 30100909
TI  - Combining Immune Checkpoint Inhibitors With Conventional Cancer Therapy.
AB  - Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer
      treatment, providing unprecedented clinical benefits. However, primary or
      acquired therapy resistance can affect up to two-thirds of patients receiving
      ICIs, underscoring the urgency to elucidate the mechanisms of treatment
      resistance and to design more effective therapeutic strategies. Conventional
      cancer treatments, including cytotoxic chemotherapy, radiation therapy, and
      targeted therapy, have immunomodulatory effects in addition to direct cancer cell
      killing activities. Their clinical utilities in combination with ICIs have been
      explored, aiming to achieve synergetic effects with improved and durable clinical
      response. Here, we will review the immunomodulatory effects of chemotherapy,
      targeted therapy, and radiation therapy, in the setting of ICI, and their
      clinical implications in reshaping modern cancer immunotherapy.

PMID- 30100913
TI  - Evolution of Climatic Related Leaf Traits in the Family Nothofagaceae.
AB  - The current relationship between leaf traits and environmental variables has been
      widely used as a proxy for climate estimates. However, it has been observed that
      the phylogenetic relationships between taxa also influence the evolution of
      climatic related leaf traits, implying that the direct use of the physiognomy
      climate relation should be corrected by their ancestor-descendant relations.
      Here, we analyze the variation of 20 leaf traits during the evolution of 27
      species in the Gondwana family Nothofagaceae. We evaluate whether the evolution
      of these traits is exclusively associated with past climate variations or whether
      they are restricted by phylogenetic relationships. Our results indicate that four
      leaf traits, associated with size and shape, had consistently a phylogenetic
      independent evolution, suggesting adaptive variation with the environment. While
      three of the traits, presented consistently phylogenetic signal and fit a
      Brownian motion or Ornstein-Uhlenbeck model of evolution, suggesting that the
      evolution of these traits is restrained by phylogenetic relationships and
      implying that phylogenetic corrections should be made for the family
      Nothofagaceae to use them as climatic proxy. Finally, this study highlights the
      importance of evaluating the evolutionary history of climatic related leaf traits
      before conducting paleoclimate estimates.

PMID- 30100912
TI  - Phytochrome and Phytohormones: Working in Tandem for Plant Growth and
      Development.
AB  - Being sessile organisms, plants need to continually adapt and modulate their rate
      of growth and development in accordance with the changing environmental
      conditions, a phenomenon referred to as plasticity. Plasticity in plants is a
      highly complex process that involves a well-coordinated interaction between
      different signaling pathways, the spatiotemporal involvement of phytohormones and
      cues from the environment. Though research studies are being carried out over the
      years to understand how plants perceive the signals from changing environmental
      conditions and activate plasticity, such remain a mystery to be resolved. Among
      all environmental cues, the light seems to be the stand out factor influencing
      plant growth and development. During the course of evolution, plants have
      developed well-equipped signaling system that enables regulation of both
      quantitative and qualitative differences in the amount of perceived light. Light
      influences essential developmental switches in plants ranging from germination or
      transition to flowering, photomorphogenesis, as well as switches in response to
      shade avoidances and architectural changes occurring during phototropism.
      Abscisic acid (ABA) is controlling seed germination and is regulated by light.
      Furthermore, circadian clock adds another level of regulation to plant growth by
      integrating light signals with different hormonal pathways. MYB96 has been
      identified as a regulator of circadian gating of ABA-mediated responses in plants
      by binding to the TIMING OF CAB EXPRESSION 1(TOC1) promoter. This review will
      present a representative regulatory model, highlight the successes achieved in
      employing novel strategies to dissect the levels of interaction and provide
      perspective for future research on phytochrome-phytohormones relationships toward
      facilitating plant growth, development, and function under abiotic-biotic
      stresses.

PMID- 30100914
TI  - Apple Intrinsic Factors Modulating the Global Regulator, LaeA, the Patulin Gene
      Cluster and Patulin Accumulation During Fruit Colonization by Penicillium
      expansum.
AB  - The mycotoxin patulin is produced in colonized tissue by Penicillium expansum
      during storage of apples and is significantly affected by environmental factors
      that contribute to its accumulation. Few reports have, however, examined the
      effect of natural intrinsic factors associated with the fruit on the production
      of patulin. Here, we find that with advancing maturity, Golden Delicious apples
      show increased concentrations of total soluble solids (TSS) from 14 to 17%
      associated with the increased expression of the global transcription factor
      involved in regulation of secondary metabolite biosynthesis in filamentous fungi,
      laeA expression and patulin accumulation. However, the apple cultivar Granny
      Smith, with similar TSS values but differing in pH levels and malic acid
      concentrations, showed reduced expression levels of laeA and the patulin
      biosynthesis gene cluster (pat genes) and patulin accumulation, suggesting a
      complexity of host factors contribution to patulin accumulation during P.
      expansum colonization. To start elucidating these apple intrinsic factors, we
      examined their in vitro impact on laeA and pat gene expression concomitant with
      patulin synthesis. Increasing sucrose concentrations from 15 to 175 mM repressed
      laeA and pat gene expression and patulin production. However, this affect was
      modified and often reversed and sometimes accentuated by changes in pH, or the
      addition of malic acid or the major apple phenolic compounds, chlorogenic acid
      and epicatechin. While the increase in malic acid from 0 to 1% increased laeA and
      pat gene expression, the decrease in pH from 3.5 to 2.5 reduced their expression.
      Also the increased laeA and pat genes expressions at increasing epicatechin
      concentrations from 0 to 1 mM, was reversed by increasing sucrose concentrations,
      all together suggesting the complexity of the interactions in vivo.

PMID- 30100915
TI  - Comparative Analysis of Complete Chloroplast Genomes of Anemoclema, Anemone,
      Pulsatilla, and Hepatica Revealing Structural Variations Among Genera in Tribe
      Anemoneae (Ranunculaceae).
AB  - Structural rearrangements of Anemone species' chloroplast genome has been
      reported based on genetic mapping of restriction sites but has never been
      confirmed by genomic studies. We used a next-generation sequencing method to
      characterize the complete chloroplast genomes of five species in the tribe
      Anemoneae. Plastid genomes were assembled using de novo assembling methods
      combined with conventional Sanger sequencing to fill the gaps. The gene order of
      the chloroplast genomes of tribe Anemoneae was compared with that of other
      Ranunculaceae species. Multiple inversions and transpositions were detected in
      tribe Anemoneae. Anemoclema, Anemone, Hepatica, and Pulsatilla shared the same
      gene order, which contained three inversions in the large single copy region
      (LSC) compared to other Ranunculaceae genera. Archiclematis, Clematis, and
      Naravelia shared the same gene order containing two inversions and one
      transposition in LSC. A roughly 4.4 kb expansion region in inverted repeat (IR)
      regions was detected in tribe Anemoneae, suggesting that this expansion event may
      be a synapomorphy for this group. Plastome phylogenomic analyses using parsimony
      and a Bayesian method with implementation of partitioned models generated a well
      resolved phylogeny of Ranunculaceae. These results suggest that evaluation of
      chloroplast genomes may result in improved resolution of family phylogenies.
      Samples of Anemone, Hepatica, and Pulsatilla were tested to form paraphyletic
      grades within tribe Anemoneae. Anemoclema was a sister clade to Clematis.
      Structual variation of the plastid genome within tribe Anemoneae provided strong
      phylogenetic information for Ranunculaceae.

PMID- 30100916
TI  - The Interface Between Wheat and the Wheat Curl Mite, Aceria tosichella, the
      Primary Vector of Globally Important Viral Diseases.
AB  - Wheat production and sustainability are steadily threatened by pests and
      pathogens in both wealthy and developing countries. This review is focused on the
      wheat curl mite (WCM), Aceria tosichella, and its relationship with wheat. WCM is
      a major pest of wheat and other cereals and a vector of at least four damaging
      plant viruses (Wheat streak mosaic virus, High plains wheat mosaic virus, Brome
      streak mosaic virus, and Triticum mosaic virus). The WCM-virus pathosystem causes
      considerable yield losses worldwide and its severity increases significantly when
      mixed-virus infections occur. Chemical control strategies are largely ineffective
      because WCM occupies secluded niches on the plant, e.g., leaf sheaths or curled
      leaves in the whorl. The challenge of effectively managing this pest-virus
      complex is exacerbated by the existence of divergent WCM lineages that differ in
      host-colonization and virus-transmission abilities. We highlight research
      progress in mite ecology and virus epidemiology that affect management and
      development of cereal cultivars with WCM- and virus-resistance genes. We also
      address the challenge of avoiding both agronomically deleterious side effects and
      selection for field populations of WCM that can overcome these resistance genes.
      This report integrates the current state of knowledge of WCM-virus-plant
      interactions and addresses knowledge gaps regarding the mechanisms driving WCM
      infestation, viral epidemics, and plant responses. We discuss the potential
      application of molecular methods (e.g., transcriptomics, epigenetics, and whole
      genome sequencing) to understand the chemical and cellular interface between the
      wheat plant and WCM-virus complexes.

PMID- 30100917
TI  - Corrigendum: Genome Sequencing and Analysis of the Peanut B-Genome Progenitor
      (Arachis ipaensis).
AB  - [This corrects the article DOI: 10.3389/fpls.2018.00604.].

PMID- 30100918
TI  - Genome-Wide Linkage Mapping Reveals QTLs for Seed Vigor-Related Traits Under
      Artificial Aging in Common Wheat (Triticum aestivum).
AB  - Long-term storage of seeds leads to lose seed vigor with slow and non-uniform
      germination. Time, rate, homogeneity, and synchrony are important aspects during
      the dynamic germination process to assess seed viability after storage. The aim
      of this study is to identify quantitative trait loci (QTLs) using a high-density
      genetic linkage map of common wheat (Triticum aestivum) for seed vigor-related
      traits under artificial aging. Two hundred and forty-six recombinant inbred lines
      derived from the cross between Zhou 8425B and Chinese Spring were evaluated for
      seed storability. Ninety-six QTLs were detected on all wheat chromosomes except
      2B, 4D, 6D, and 7D, explaining 2.9-19.4% of the phenotypic variance. These QTLs
      were clustered into 17 QTL-rich regions on chromosomes 1AL, 2DS, 3AS (3), 3BS,
      3BL (2), 3DL, 4AS, 4AL (3), 5AS, 5DS, 6BL, and 7AL, exhibiting pleiotropic
      effects. Moreover, 10 stable QTLs were identified on chromosomes 2D, 3D, 4A, and
      6B (QaMGT.cas-2DS.2, QaMGR.cas-2DS.2, QaFCGR.cas-2DS.2, QaGI.cas-3DL, QaGR.cas
      3DL, QaFCGR.cas-3DL, QaMGT.cas-4AS, QaMGR.cas-4AS, QaZ.cas-4AS, and QaGR.cas
      6BL.2). Our results indicate that one of the stable QTL-rich regions on
      chromosome 2D flanked by IWB21991 and IWB11197 in the position from 46 to 51 cM,
      presenting as a pleiotropic locus strongly impacting seed vigor-related traits
      under artificial aging. These new QTLs and tightly linked SNP markers may provide
      new valuable information and could serve as targets for fine mapping or markers
      assisted breeding.

PMID- 30100919
TI  - Associations Between XPD Lys751Gln Polymorphism and Leukemia: A Meta-Analysis.
AB  - Objectives: The aim of the present study was to define the potential relationship
      between xeroderma pigmentosum group D (XPD) Lys751Gln polymorphisms and the risk
      of leukemia. Methods: A comprehensive search of Pubmed, Web of Science, EBSCO,
      the Cochrane Library and China National Knowledge Infrastructure was conducted to
      identify original articles published before March 2017 concerning the association
      between XPD Lys751Gln polymorphisms and leukemia risk. A literature quality
      assessment was performed using the Newcastle-Ottawa Scale. Heterogeneity across
      studies was assessed using I2 statistics. Random- or fixed-effects models were
      used to calculate pooled odds ratios (ORs) in the presence or absence of
      heterogeneity, respectively. Sensitivity analysis was used to assess the
      influence of individual studies on the pooled estimate. Publication bias was
      investigated using funnel plots and Egger's regression test. All data analyses
      were performed using Stata 14.0 and Revman 5.3. Results: Fourteen studies with a
      total of 7525 participants (2,757 patients; 4,768 controls) were included in this
      meta-analysis. We found that XPD Lys751Gln polymorphisms significantly increased
      the risk of developing leukemia in both dominant OR = 1.21, 95%CI [1.10-1.35], P
      <= 0.001) and heterozygote (OR = 1.22, 95%CI [1.09-1.36], P <= 0.001) model. An
      allele model showed a borderline significant increase in leukemia risk (OR =
      1.13, 95%CI [1.00-1.27], P = 0.05). A subgroup analysis revealed a consistent
      association between XPD Lys751Gln polymorphisms and leukemia risk for some
      genetic models in Caucasian populations, adult or chronic groups, and in almost
      all models of childhood or acute groups. Conclusion: Our results indicate that
      XPD Lys751Gln polymorphism increases the risk of leukemia, especially in
      childhood and acute cases.

PMID- 30100921
TI  - A comparison of semi-quantitative methods suitable for establishing volatile
      profiles.
AB  - Background: Full scent profiles emitted by living tissues can be screened by
      using total ion chromatograms generated in full scan mode and gas chromatography
      mass spectrometry technique using Headspace Sorptive Extraction. This allows the
      identification of specific compounds and their absolute quantification or
      relative abundance. Quantifications ideally should be based on calibration curves
      using standards for each compound. However, the unpredictable composition of
      Volatile Organic Compounds (VOCs) and lack of standards make this approach
      difficult. Researchers studying scent profiles therefore concentrate on
      identifying specific scent footprints i.e. relative abundance rather than
      absolute quantities. We compared several semi-quantitative methods: external
      calibration curves generated in the sampling system and by liquid addition of
      standards to stir bars, total integrated peak area per fresh weight (FW),
      normalized peak area per FW, semi-quantification based on internal standard
      abundance, semi-quantification based on the nearest n-alkane and percentage of
      emission. Furthermore, we explored the usage of nearest components and single
      calibrators for semi-quantifications. Results: Any of the semi-quantification
      methods based on a standard produced similar or even identical results compared
      to quantification by a true-standard for a compound, except for the method based
      on standard addition. Each method beholds advantages and disadvantages regarding
      level of accuracy, experimental variability, acceptance and retrieved quantities.
      Conclusions: Our data shows that, except for the method of standard addition to
      the biological sample, the rest of the semi-quantification methods studied give
      highly similar statistical results. Any of the methodologies presented here can
      therefore be considered as valid for scent profiling. Regarding relative
      proportions of VOCs, the generation of calibration curves for each compound
      analysed is not necessary.

PMID- 30100920
TI  - Genetic Susceptibility to Neurodegeneration in Amazon: Apolipoprotein E
      Genotyping in Vulnerable Populations Exposed to Mercury.
AB  - Human exposure to mercury is a serious problem of public health in Amazon. As in
      other vulnerable populations throughout the world, Amazonian riverine populations
      are chronically exposed to this metal and some symptoms of mercury intoxication
      were already detected in these populations. However, studies on the genetic
      susceptibility to mercury toxicity in the Amazon are scarce, and they tested a
      limited number of individuals. In this context, apolipoprotein E gene (APOE) is a
      key element with a well-established association among their alleles and the
      neurodegenerative consequences of mercury intoxication. However, no studies have
      addressed APOE genotyping in Amazonian exposed populations. Additionally,
      epidemiological studies with APOE genotyping in Amazon have been restricted to
      indigenous populations. Therefore, this work analyzed for the first time the
      genotypic and allelic profiles of APOE in Amazonian riverine populations
      chronically exposed to mercury. Eight hundred and twenty three individuals were
      enrolled in our study donating blood (794) and/or hair (757). APOE genotyping was
      analyzed by real-time PCR. Total mercury and mercury species were quantified by
      ICP-MS and GC-pyro-AFS, respectively. Genomic ancestry markers were evaluated by
      multiplex-PCR reaction, separated by capillary electrophoresis on the ABI 3130
      Genetic Analyzer instrument and analyzed on GeneMapper ID v3.2. The ??3 and
      ??3/??3 were the most frequent allele and genotype, respectively, followed by ??4
      allele and ??3/??4 genotype. Only ??2/??2 genotype was not found, suggesting that
      the absence of this genotype is a generalized phenomenon in Amazon. Also, our
      data supported an association between the presence of APOE4 and the Amerindian
      origin in these populations. Fifty-nine individuals were identified at maximum
      risk with levels of mercury above 10 MUg/g and the presence of APOE4.
      Interestingly, among individuals with high mercury content, APOE4-carriers had
      high mercury levels than APOE2-carriers, pointing to a different heavy metal
      accumulation according to the APOE allele. These data suggest that APOE4, in
      addition to a possible pharmacodynamic effect, may influence pharmacokinetically
      the mercury exposure causing its higher accumulation and leading to worse
      deleterious consequences. Our results may aid in the development of prevention
      strategies and health policy decision-making regarding these at-risk vulnerable
      populations.

PMID- 30100923
TI  - From the small screen to breast cancer screening: examining the effects of a
      television storyline on awareness of genetic risk factors.
AB  - Background: The topic of breast cancer genetics entered the public discourse
      following Angelina Jolie's 2013 announcement that she carries the BRCA1 mutation
      and underwent a prophylactic double mastectomy to reduce her breast cancer risk.
      A year prior to Jolie's announcement, the teen drama 90210 ran an eight-episode
      story arc on the BRCA gene mutations. This study focuses on an evaluation of the
      impact of this particular media text within the broader context of research on
      the persuasive effects of entertainment narratives (i.e. entertainment
      education). Method: The evaluation consisted of two complementary studies of
      adult women: a pre-test/post-test study using a panel sample of regular
      television viewers who were directed to watch a particular episode (Study 1), and
      a cross-sectional study using a convenience sample of frequent 90210 viewers
      (Study 2). Results: In both studies, storyline exposure was associated with
      increased knowledge (familiarity with the BRCA gene, knowledge about mastectomy).
      Study 1 additionally saw evidence of increased fears regarding the consequences
      of the BRCA gene and intentions to talk to a doctor. In Study 2, the number of
      episodes viewed was positively related to both knowledge and behavior (finding
      out about one's family history of breast cancer). Conclusions: These findings
      suggest that despite unprecedented changes in the ways audiences engage with and
      consume entertainment media, television narratives remain a powerful method of
      educating viewers about health risks and inspiring them to take action.

PMID- 30100924
TI  - A multi-objective gene clustering algorithm guided by apriori biological
      knowledge with intensification and diversification strategies.
AB  - Background: Biologists aim to understand the genetic background of diseases,
      metabolic disorders or any other genetic condition. Microarrays are one of the
      main high-throughput technologies for collecting information about the behaviour
      of genetic information on different conditions. In order to analyse this data,
      clustering arises as one of the main techniques used, and it aims at finding
      groups of genes that have some criterion in common, like similar expression
      profile. However, the problem of finding groups is normally multi dimensional,
      making necessary to approach the clustering as a multi-objective problem where
      various cluster validity indexes are simultaneously optimised. They are usually
      based on criteria like compactness and separation, which may not be sufficient
      since they can not guarantee the generation of clusters that have both similar
      expression patterns and biological coherence. Method: We propose a Multi
      Objective Clustering algorithm Guided by a-Priori Biological Knowledge (MOC
      GaPBK) to find clusters of genes with high levels of co-expression, biological
      coherence, and also good compactness and separation. Cluster quality indexes are
      used to optimise simultaneously gene relationships at expression level and
      biological functionality. Our proposal also includes intensification and
      diversification strategies to improve the search process. Results: The
      effectiveness of the proposed algorithm is demonstrated on four publicly
      available datasets. Comparative studies of the use of different objective
      functions and other widely used microarray clustering techniques are reported.
      Statistical, visual and biological significance tests are carried out to show the
      superiority of the proposed algorithm. Conclusions: Integrating a-priori
      biological knowledge into a multi-objective approach and using intensification
      and diversification strategies allow the proposed algorithm to find solutions
      with higher quality than other microarray clustering techniques available in the
      literature in terms of co-expression, biological coherence, compactness and
      separation.

PMID- 30100922
TI  - Congenital aniridia: etiology, manifestations and management.
AB  - Congenital aniridia manifests as total or partial absence of the iris caused most
      commonly by mutations in PAX6, FOXC1, PITX2, and CYP1B1. Recently two new genes,
      FOXD3 and TRIM44, have also been implicated in isolated studies. We discuss the
      genotype-phenotype correlations for the main implicated genes. Classic aniridia
      is a panocular condition, which includes aniridia, cataract, corneal pannus,
      foveal, and optic nerve hypoplasia associated with mutations in the PAX6 gene.
      Classical aniridia is due to PAX6 mutations, while other genes contribute to
      aniridia-like phenotypes. We review the challenges involved in the management of
      aniridia, and discuss various surgical interventions. The clinical importance of
      defining the genotype in cases of congenital aniridia has become acutely apparent
      with the advent of possible therapies for classical aniridia, which are
      discussed.

PMID- 30100926
TI  - Practical guidance for treatment of patients with diabetes using flash glucose
      monitoring: a pilot study.
AB  - Background: Flash glucose monitoring (FGM) is a factory-calibrated, blood glucose
      measuring sensor system for patients with diabetes. We aimed to investigate the
      correlation between the sensor glucose (SG) value obtained using an FGM device
      and the traditional self-monitoring of blood glucose (SMBG) value. Methods: In 30
      patients with diabetes under insulin treatment, SG and SMBG values were measured
      for 2 weeks, and the correlation between the values was analyzed. Results: The
      mean number of accumulated measurements of SG values was 1223.2 +/- 193.0,
      whereas that of the SMBG values was 49.2 +/- 21.3. Although SG and SMBG values
      showed a favorable correlation (R2  = 0.8413), SG values were lower than SMBG
      values by an average of 7.9 +/- 29.8 mg/dL. The correlation patterns fell into
      four types: low type (SG values lower than SMBG values; n = 12), high type (SG
      values higher than SMBG values; n = 3), cross type (the slope of the two
      regression lines crossed at a certain measurement value; n = 14), and matching
      type (the values overlapped; n = 1). Conclusions: Recognition of the
      characteristic correlation patterns between SG and SMBG values is indispensable
      for certified diabetes educators to provide appropriate treatment guidance to
      patients with diabetes.

PMID- 30100925
TI  - Effective strategies for encouraging behavior change in people with diabetes.
AB  - Behavioral management of diabetes leads to better health outcomes. This paper
      reviews the available literature on facilitators of behavior change in people
      with diabetes and highlights approaches and strategies diabetes care providers
      can utilize. The research and clinical evidence points to the critical nature of
      considering the content and structure of recommendations, and utilizing problem
      solving and teamwork approaches. Furthermore, close attention to individual and
      community factors will optimize behavior change. These factors include health
      literacy, community infrastructure, support within the family, and whether there
      are co-occurring eating and mood issues. Recommendations are provided to optimize
      communication and embed behavior change approaches in clinical and community
      encounters.

PMID- 30100927
TI  - F-CphI represents a new homing endonuclease family using the Endo VII catalytic
      motif.
AB  - Background: There are six known families of homing endonucleases, LAGLIDADG, GIY
      YIG, HNH, His-Cys box, PD-(D/E)-XK, and EDxHD, which are characterized by their
      conserved residues. Previously, we discovered a novel homing endonuclease F-CphI
      encoded by ORF177 of cyanophage S-PM2. F-CphI does not resemble any characterized
      homing endonucleases. Instead, the C-terminus of F-CphI aligns well with the N
      terminal catalytic domain of a Holliday junction DNA resolvase, phage T4
      endonuclease VII (Endo VII). Results: A PSI-BLAST search resulted in a total of
      313 Endo VII motif-containing sequences in sequenced genomes. Multiple sequence
      alignment showed that the catalytically important residues of T4 Endo VII were
      all well conserved in these proteins. Our site-directed mutagenesis studies
      further confirmed that the catalytically important residues of T4 Endo VII were
      also essential for F-CphI activity, and thus F-CphI might use a similar protein
      fold as Endo VII for DNA cleavage. A phylogenetic tree of the Endo VII motif
      containing sequences showed that putative resolvases grouped into one clade while
      putative homing endonucleases and restriction endonucleases grouped into another
      clade. Conclusions: Based on the unique conserved residues, we proposed that F
      CphI represents a new homing endonuclease family, which was named the DHHRN
      family. Our phylogenetic analysis could be used to predict the functions of many
      previously unknown proteins.

PMID- 30100928
TI  - A Comparative Study of In-Air Trajectories at Short and Long Distances in Online
      Handwriting.
AB  - Existing literature about online handwriting analysis to support pathology
      diagnosis has taken advantage of in-air trajectories. A similar situation
      occurred in biometric security applications where the goal is to identify or
      verify an individual using his signature or handwriting. These studies do not
      consider the distance of the pen tip to the writing surface. This is due to the
      fact that current acquisition devices do not provide height formation. However,
      it is quite straightforward to differentiate movements at two different heights
      (a) short distance: height lower or equal to 1 cm above a surface of digitizer,
      the digitizer provides x and y coordinates; (b) long distance: height exceeding 1
      cm, the only information available is a time stamp that indicates the time that a
      specific stroke has spent at long distance. Although short distance has been used
      in several papers, long distances have been ignored and will be investigated in
      this paper. In this paper, we will analyze a large set of databases (BIOSECUR-ID,
      EMOTHAW, PaHaW, OXYGEN-THERAPY, and SALT), which contain a total amount of 663
      users and 17,951 files. We have specifically studied (a) the percentage of time
      spent on-surface, in-air at short distance, and in-air at long distance for
      different user profiles (pathological and healthy users) and different tasks; (b)
      the potential use of these signals to improve classification rates. Our
      experimental results reveal that long distance movements represent a very small
      portion of the total execution time (0.5% in the case of signatures and 10.4% for
      uppercase words of BIOSECUR-ID, which is the largest database). In addition,
      significant differences have been found in the comparison of pathological versus
      control group for letter "l" in PaHaW database (p = 0.0157) and crossed pentagons
      in SALT database (p = 0.0122).

PMID- 30100930
TI  - Self-compassion and Psychological Distress in Adolescents-a Meta-analysis.
AB  - Research indicates that self-compassion is relevant to adolescents' psychological
      well-being, and may inform the development of mental health and well-being
      interventions for youth. This meta-analysis synthesises the existing literature
      to estimate the magnitude of effect for the association between self-compassion
      and psychological distress in adolescents. Our search identified 19 relevant
      studies of adolescents (10-19 years; N = 7049) for inclusion. A large effect size
      was found for an inverse relationship between self-compassion and psychological
      distress indexed by anxiety, depression, and stress (r = - 0.55; 95% CI  - 0.61
      to - 0.47). The identified studies were highly heterogeneous, however sensitivity
      analyses indicated that correction for publication bias did not significantly
      alter the pattern of results. These findings replicate those in adult samples,
      suggesting that lack of self-compassion may play a significant role in causing
      and/or maintaining emotional difficulties in adolescents. We conclude that self
      compassion may be an important factor to target in psychological distress and
      well-being interventions for youth.

PMID- 30100929
TI  - A Systematic Review and Meta-analysis of the Effects of Meditation on Empathy,
      Compassion, and Prosocial Behaviors.
AB  - Increased attention has focused on methods to increase empathy, compassion, and
      pro-social behavior. Meditation practices have traditionally been used to
      cultivate pro-social outcomes, and recently investigations have sought to
      evaluate their efficacy for these outcomes. We conducted a systematic review and
      meta-analysis of meditation for pro-social emotions and behavior. A literature
      search was conducted in PubMed, MEDLINE, PsycINFO, CINAHL, Embase, and Cochrane
      databases (inception-April 2016) using the search terms: mindfulness, meditation,
      mind-body therapies, tai chi, yoga, MBSR, MBCT, empathy, compassion, love,
      altruism, sympathy, or kindness. Randomized controlled trials in any population
      were included (26 studies with 1,714 subjects). Most were conducted among healthy
      adults (n=11) using compassion or loving kindness meditation (n=18) over 8
      12weeks (n=12) in a group format (n=17). Most control groups were wait-list or no
      treatment (n=15). Outcome measures included self-reported emotions (e.g.,
      composite scores, validated measures) and observed behavioral outcomes (e.g.,
      helping behavior in real-world and simulated settings). Many studies showed a low
      risk of bias. Results demonstrated small to medium effects of meditation on self
      reported (SMD = .40, p < .001) and observable outcomes (SMD = .45, p < .001) and
      suggest psychosocial and neurophysiological mechanisms of action. Subgroup
      analyses also supported small to medium effects of meditation even when compared
      to active control groups. Clinicians and meditation teachers should be aware that
      meditation can improve positive pro-social emotions and behaviors.

PMID- 30100931
TI  - Mindfulness-Based Cognitive Therapy for Young People and Their Carers: a Mixed
      Method Feasibility Study.
AB  - We aimed to evaluate whether mindfulness-based cognitive therapy (MBCT) was
      feasible and acceptable for young people, their parents and the clinicians
      working with them; whether a parallel course for parents was a useful addition;
      and whether attendance at MBCT was associated with improved outcomes. The design
      was a mixed-method service evaluation of an eight-session MBCT programme for
      young people who were recovering from depression. The course was a manualised
      eight-session group intervention. Both young people (n = 18) and parents (n = 21)
      completed validated measures before and after the course. Semi-structured
      interviews were completed with some group participants and clinical staff working
      in the service. Care records were searched for additional contact following the
      intervention. Qualitative data from young people, parents and clinicians
      suggested that MBCT was acceptable and feasible and provided strategies to cope.
      The parent course was reported to provide personal support to parents and helped
      them cope with their child's depression whilst also impacting the family,
      promoted shared understanding of depression and strategies to combat it and
      addressed intergenerational aspects of depression. Eighty-four per cent of
      participants attended at least 6/8 sessions, and 48% required no further
      intervention within the following year. Young people had statistically
      significant improvements across all outcome measures, whilst parents had
      statistically significant improvements in rumination, self-compassion and
      decentring.

PMID- 30100933
TI  - Which Facets of Mindfulness Protect Individuals from the Negative Experiences of
      Obsessive Intrusive Thoughts?
AB  - Obsessive intrusive thoughts (OITs) are experienced by the majority of the
      general population, and in their more extreme forms are characteristic of
      obsessive-compulsive disorder (OCD). These cognitions are said to exist on a
      continuum that includes differences in their frequency and associated distress.
      The key factors that contribute to an increased frequency and distress are how
      the individual appraises and responds to the OIT. Facets of mindfulness, such as
      nonjudgment and nonreactivity, offer an alternative approach to OITs than the
      negative appraisals and commonly utilised control strategies that often
      contribute to distress. Clarifying the role of facets of mindfulness in relation
      to these cognitions offers a means to elucidate individual characteristics that
      may offer protection from distress associated with OITs. A sample of nonclinical
      individuals (n = 583) completed an online survey that assessed their experiences
      of OITs, including frequency, emotional reaction and appraisals, and trait
      mindfulness. The findings from a series of multiple regression analyses confirmed
      that specific facets of mindfulness relating to acting with awareness and
      acceptance (nonjudgment and nonreactivity) consistently predicted less frequent
      and distressing experiences of OITs. In contrast, the observe facet emerged as a
      consistent predictor of negative experiences of OITs. These findings suggest that
      acting with awareness and acceptance may confer protective characteristics in
      relation to OITs, but that the observe facet may reflect a hypervigilance to
      OITs. Mindfulness-based prevention and intervention for OCD should be tailored to
      take account of the potential differential effects of increasing specific facets
      of mindfulness.

PMID- 30100932
TI  - Additive Effects of 3,4-Methylenedioxymethamphetamine (MDMA) and Compassionate
      Imagery on Self-Compassion in Recreational Users of Ecstasy.
AB  - 3,4-Methylenedioxymethylamphetamine (MDMA;'ecstasy') produces prosocial
      subjective effects that may extend to affiliative feelings towards the self.
      Behavioural techniques can produce similar self-directed affiliation. For
      example, compassionate imagery (CI) and ecstasy reduce self-criticism and
      increase self-compassion to a similar extent, with the effects of CI enhanced in
      the presence of ecstasy. Here, we examine self-compassion and self-criticism in
      recreational users who consumed chemically verified MDMA in a within-subjects
      crossover study. In a naturalistic setting, polydrug-using participants performed
      a self-focused CI exercise on two occasions separated by >=6 days: once having
      consumed self-sourced MDMA and once not. Effects on state self-criticism, self
      compassion and emotional empathy were assessed before and after MDMA use (or over
      an extended baseline period on the occasion that MDMA was not consumed) and
      reassessed after CI. In participants (n = 20; 8 women) whose ecstasy contained
      MDMA and no other drug, CI and MDMA appeared to separately increase emotional
      empathy (to critical facial expressions) and self-compassion. The effects of CI
      and MDMA on self-compassion also appeared to be additive. Establishing the
      observed effects in controlled studies will be critical for determining the
      combined utility of these approaches in fostering adaptive self-attitudes in a
      therapeutic context.

PMID- 30100935
TI  - Investigating the Specific Effects of an Online Mindfulness-Based Self-Help
      Intervention on Stress and Underlying Mechanisms.
AB  - Previous research examining the effects of mindfulness-based interventions (MBIs)
      and their mechanisms of change has been hampered by failure to control for non
      specific factors, such as social support and interaction with group members,
      facilitator contact and expectation of benefit, meaning that it remained possible
      that benefits of MBIs could have been attributable, perhaps entirely, to non
      specific elements. This experimental study examined the effects of a 2-week
      online mindfulness-based self-help (MBSH) intervention compared to a well-matched
      classical music control condition and a waitlist control condition on perceived
      stress. This study also tested mindfulness, self-compassion and worry as
      mechanisms of the effects of MBSH versus both control conditions on stress.
      University students and staff (N = 214) were randomised to MBSH, classical music,
      or waitlist conditions and completed self-report measures pre-, mid- and post
      intervention. Post-intervention, MBSH was found to significantly reduce stress
      compared to both control conditions. Bootstrapping-based mediation analyses used
      standardised residualised change scores for all variables, with mediators
      computed as change from baseline to mid-intervention, and the outcome computed as
      change from baseline to post-intervention. Changes in mindfulness, self
      compassion and worry were found to significantly mediate the effects of MBSH
      versus both control conditions on changes in stress. Findings suggest that
      cultivating mindfulness specifically confers benefits to stress and that these
      benefits may occur through improving theorised mechanisms.

PMID- 30100934
TI  - A Randomised Controlled Trial of a Brief Online Mindfulness-Based Intervention in
      a Non-clinical Population: Replication and Extension.
AB  - Building on previous research, this study compared the effects of two brief,
      online mindfulness-based interventions (MBIs; with and without formal meditation
      practice) and a no intervention control group in a non-clinical sample. One
      hundred and fifty-five university staff and students were randomly allocated to a
      2-week, self-guided, online MBI with or without mindfulness meditation practice,
      or a wait list control. Measures of mindfulness, perceived stress, perseverative
      thinking and anxiety/depression symptoms within were administered before and
      after the intervention period. Intention to treat analysis identified significant
      differences between groups on change over time for all measured outcomes.
      Participation in the MBIs was associated with significant improvements in all
      measured domains (all ps < 0.05), with effect sizes in the small to medium range
      (0.25 to 0.37, 95% CIs 0.11 to 0.56). No significant changes on these measures
      were found for the control group. Change in perseverative thinking was found to
      mediate the relationship between condition and improvement on perceived stress
      and anxiety/depression symptom outcomes. Contrary to our hypotheses, no
      differences between the intervention conditions were found. Limitations of the
      study included reliance on self-report data, a relatively high attrition rate and
      absence of a longer-term follow-up. This study provides evidence in support of
      the feasibility and effectiveness of brief, self-guided MBIs in a non-clinical
      population and suggests that reduced perseverative thinking may be a mechanism of
      change. Our findings provide preliminary evidence for the effectiveness of a
      mindfulness psychoeducation condition, without an invitation to formal
      mindfulness meditation practice. Further research is needed to confirm and better
      understand these results and to test the potential of such interventions.

PMID- 30100936
TI  - Effectiveness of Mindfulness-Based Stress Reduction in a Self-Selecting and Self
      Paying Community Setting.
AB  - We aimed to evaluate the effectiveness of Mindfulness-Based Stress Reduction
      (MBSR) when implemented in a community setting as a self-referred and self-paid
      course. Pre-post changes and Cohen's d effect sizes were calculated for
      questionnaire measures of mindfulness, perceived stress, and symptoms of anxiety
      and depression. We compared these effect sizes with those from intervention
      groups in randomized controlled trials (RCTs), with populations similar to our
      study sample. These RCTs reported significant effects of MBSR compared to control
      condition. MBSR was delivered in three different Danish cities by ten different
      MBSR teachers with various professional backgrounds and MBSR teaching experience.
      One hundred and thirty-two participants were included in the study: 79% were
      women, mean age 45 +/- 10.4 years, 75% of the participants had more than 15 years
      of education, 38% had a Perceived Stress Scale (PSS) score>=18, and 27% had a
      history of mental disorder. Post MBSR, the proportion of participants with a
      PSS>=18 decreased by 16% points (95%CI -26 to -6), p = 0.0032. Within-group
      effect sizes for (i) the total study population (ii) the subgroup with PSS>=18 at
      baseline (iii) intervention group in reference RCTs were as follows: PSS: d =
      0.50:1.47:1.00, Symptom Check List 5: d = 0.48:0.81:0.77, Five Facet Mindfulness
      Questionnaire: d = 0.67:1.09:1.00. Our results showed that MBSR was effective.
      The effects were largest among the participants reporting highest perceived
      stress level at baseline. Our participants were mainly women who were middle
      aged, with high educational levels, and more perceived stress and a greater
      history of mental disorder than the general population, and who were able to seek
      out and pay for an MBSR course. Reaching vulnerable groups with a clear need for
      stress management will, however, require other implementation strategies.

PMID- 30100937
TI  - Factors Associated with Dose Determination of Radioactive Iodine Therapy for
      Differentiated Thyroid Cancer.
AB  - Radioactive iodine (RAI) therapy for differentiated thyroid cancer has been
      successfully used for more than 70 years. However, there is still plenty of
      controversy surrounding the use and doses of radioiodine. There is insufficient
      evidence to answer the questions. Recent American Thyroid Association (ATA)
      guidelines seem to favor low-dose RAI, based on recent clinical trials and meta
      analyses. However, long-term follow-up data remains limited, and there are
      additional factors we should consider that might affect the efficacy of RAI
      therapy. Therefore, until sufficient data are available, it is necessary to
      remain cautious about determining RAI doses by considering multiple patient
      specific variables.

PMID- 30100940
TI  - Measurement of 68Ga-DOTATOC Uptake in the Thoracic Aorta and Its Correlation with
      Cardiovascular Risk.
AB  - Purpose: 68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic
      acid-d-Phe1-Tyr3-octreotide (68Ga-DOTATOC) is taken up by activated macrophages,
      which accumulate in active inflammatory lesions. The purpose of this study was to
      investigate the feasibility of 68Ga-DOTATOC PET/CT for assessment of vulnerable
      plaque, by evaluating correlation between aortic uptake of 68Ga-DOTATOC and
      cardiovascular risk factors. Methods: Fifty patients with neuroendocrine tumors
      who underwent 68Ga-DOTATOC PET/CT were retrospectively enrolled. The uptakes in
      the thoracic aorta were measured by two methods: multi-sample region-of-interest
      (ROI) method and single volume-of-interest (VOI) method. TBRmax-avg, TBRmean-avg,
      TBRmax-VOI, and TBRmean-VOI were defined by maximum and mean target-to-background
      ratio (TBR) from the multi-sample ROI method and the single VOI method,
      respectively. Results: Framingham risk score (FRS) exhibited significant
      correlations with TBRmax-avg and TBRmean-avg, as well as TBRmax-VOI (r = 0.3389
      0.4593, P < 0.05 for all). TBRmax-avg and TBRmax-VOI were significantly higher in
      high FRS group than in low FRS group (1.48 +/- 0.21 vs. 1.70 +/- 0.17, P < 0.001
      for TBRmax-avg and 1.90 +/- 0.33 vs. 2.25 +/- 0.36, P = 0.002 for TBRmax-VOI).
      TBR exhibited high correlations between the two measuring methods (r = 0.9684, P
      < 0.001 for TBRmean-avg and TBRmean-VOI and r = 0.8681, P < 0.001 for TBRmax-avg
      and TBRmax-VOI). Conclusions: 68Ga-DOTATOC uptake in the thoracic aorta exhibited
      a significant correlation with cardiovascular risk factors, which suggests the
      feasibility of 68Ga-DOTATOC PET for vulnerable plaque imaging, with a simple
      measurement of the single VOI method that is comparable to the multi-sample ROI
      based approach.

PMID- 30100941
TI  - Response Prediction of Altered Thyroglobulin Levels After Radioactive Iodine
      Therapy Aided by Recombinant Human Thyrotropin in Patients with Differentiated
      Thyroid Cancer.
AB  - Purpose: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues
      after radioactive iodine (RAI) therapy in patients with differentiated thyroid
      carcinoma (DTC). We investigated whether altered levels of serum Tg after
      recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic
      marker in patients with DTC. Methods: We evaluated 68 patients who underwent RAI
      therapy after total thyroidectomy. Serum Tg levels were measured just before RAI
      administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg
      level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury
      effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level
      divided by that on D0Tg. The therapeutic responses were classified as acceptable
      or non-acceptable. Finally, we investigated which clinicopathologic parameters
      were associated with therapeutic response. Results: At the follow-up examination,
      an acceptable response was observed in 50 patients (73.5%). Univariate analysis
      revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable
      vs. non-acceptable responses, 21.9 +/- 33.6 vs. 3.8 +/- 6.5; P = 0.006). In
      multivariate analysis, only ratioTg significantly predicted an acceptable
      response (odds ratio 1.104; 95% confidence interval 1.005-1.213; P = 0.040). A
      ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%,
      specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P =
      0.006). Conclusions: Altered levels of serum Tg after RAI therapy, calculated as
      the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in
      patients with DTC.

PMID- 30100943
TI  - Capabilities of the Monte Carlo Simulation Codes for Modeling of a Small Animal
      SPECT Camera.
AB  - Purpose: This study aims to compare Monte Carlo-based codes' characteristics in
      the determination of the basic parameters of a high-resolution single photon
      emission computed tomography (HiReSPECT) scanner. Methods: The geometry of this
      dual-head gamma camera equipped with a pixelated CsI(Na) scintillator and lead
      hexagonal hole collimator were accurately described in the GEANT4 Application for
      the Tomographic Emission (GATE), Monte Carlo N-particle extended (MCNP-X), and
      simulation of imaging nuclear detectors (SIMIND) codes. We implemented simulation
      procedures similar to the experimental test for calculation of the energy
      spectra, spatial resolution, and sensitivity of HiReSPECT by using 99mTc sources.
      Results: The energy resolutions simulated by SIMIND, MCNP-X, and GATE were 17.53,
      19.24, and 18.26%, respectively, while it was calculated at 19.15% in
      experimental test. The average spatial resolutions of the HiReSPECT camera at 2.5
      cm from the collimator surface simulated by SIMIND, MCNP-X, and GATE were 3.18,
      2.9, and 2.62 mm, respectively, while this parameter was reported at 2.82 mm in
      the experiment test. The sensitivities simulated by SIMIND, MCNP-X, and GATE were
      1.44, 1.27, and 1.38 cps/MUCi, respectively, on the collimator surface.
      Conclusions: Comparison between simulation and experimental results showed that
      among these MC codes, GATE enabled to accurately model realistic SPECT system and
      electromagnetic physical processes, but it required more time and hardware
      facilities to run simulations. SIMIND was the most flexible and user-friendly
      code to simulate a SPECT camera, but it had limitations in defining the non
      conventional imaging device. The most important characteristics like time and
      speed of simulation, preciseness of results, and user-friendliness should be
      considered during simulations.

PMID- 30100942
TI  - A Comparison of the Accuracy of Different Single Plasma Sample Methods for
      Measuring Glomerular Filtration Rate Using 51Cr-EDTA in Children.
AB  - Purpose: Among the different methods of measuring glomerular filtration rate
      (GFR) using 51Cr-ethylenediaminetetraacetic acid clearance, the two-plasma-sample
      method (TPSM) is widely used, and highly accurate. The single-plasma-sample
      method (SPSM) is occasionally used for simplicity, at the expense of accuracy.
      Our aims were (1) to investigate the correlation and (2) to compare the accuracy
      of six known SPSMs in pediatric patients in reference to TPSM. Methods: We
      retrospectively reviewed 122 pediatric cases (65 boys, age 7.3 +/- 4.6 years) and
      analyzed 307 GFR measurements. SPSMs included Groth and Aasted at 120 min, Ham at
      120 min, Christensen and Groth at 120 and 240 min, and Jacobsson at 120 and 240
      min. Reference GFR (GFRref) was defined using TPSM GFR corrected by the Jodal and
      Brochner-Mortensen equation. GFRref < 30 mL min-1 1.73 m-2 were excluded. The
      standard error of the estimate (SEE) and the number of cases with differences >
      10% (N10%) were used to evaluate accuracy. Results: SPSMs generally correlated
      well with GFRref (r = 0.92~0.99) and were relatively accurate (SEE = 9.21~15.60).
      Groth and Aasted showed the smallest SEE, while Jacobsson at 240 min showed the
      smallest N10% for all GFRref ranges. As for the decreased GFRref, Ham was most
      accurate followed by Jacobsson at 240 min. Conclusions: Jacobsson at 240 min
      provided good accuracy in all GFRref ranges and was well correlated with TPSM.
      Jacobsson at 240 min might be the most appropriate method to substitute for TPSM
      in pediatric patients. Ham could be an alternative in patients with impaired
      renal function.

PMID- 30100938
TI  - Current Consensus on I-131 MIBG Therapy.
AB  - Metaiodobenzylguanidine (MIBG) is structurally similar to the neurotransmitter
      norepinephrine and specifically targets neuroendocrine cells including some
      neuroendocrine tumors. Iodine-131 (I-131)-labeled MIBG (I-131 MIBG) therapy for
      neuroendocrine tumors has been performed for more than a quarter-century. The
      indications of I-131 MIBG therapy include treatment-resistant neuroblastoma (NB),
      unresectable or metastatic pheochromocytoma (PC) and paraganglioma (PG),
      unresectable or metastatic carcinoid tumors, and unresectable or metastatic
      medullary thyroid cancer (MTC). I-131 MIBG therapy is one of the considerable
      effective treatments in patients with advanced NB, PC, and PG. On the other hand,
      I-131 MIBG therapy is an alternative method after more effective novel therapies
      are used such as radiolabeled somatostatin analogs and tyrosine kinase inhibitors
      in patients with advanced carcinoid tumors and MTC. No-carrier-aided (NCA) I-131
      MIBG has more favorable potential compared to the conventional I-131 MIBG.
      Astatine-211-labeled meta-astatobenzylguanidine (At-211 MABG) has massive
      potential in patients with neuroendocrine tumors. Further studies about the
      therapeutic protocols of I-131 MIBG including NCA I-131 MIBG in the clinical
      setting and At-211 MABG in both the preclinical and clinical settings are needed.

PMID- 30100939
TI  - Emerging Tracers for Nuclear Cardiac PET Imaging.
AB  - Myocardial perfusion imaging using positron emission tomography (PET) has several
      advantages over single photon emission computed tomography (SPECT). The recent
      advances in SPECT technology have shown promise, but there is still a large need
      for PET in the clinical management of coronary artery disease (CAD). Especially,
      absolute quantification of myocardial blood flow (MBF) using PET is extremely
      important. In spite of considerable advances in the diagnosis of CAD, novel PET
      radiopharmaceuticals remain necessary for the diagnosis of CAD because clinical
      use of current cardiac radiotracers is limited by their physical characteristics,
      such as decay mode, emission energy, and half-life. Thus, the use of a
      radioisotope that has proper characteristics and a proper half-life to develop
      myocardial perfusion agents could overcome these limitations. In this review, the
      current state of cardiac PET and a general overview of novel 18F or 68Ga-labeled
      radiotracers, including their radiosynthesis, in vivo characterization, and
      evaluation, are provided. The future perspectives are discussed in terms of their
      potential usefulness based on new image analysis methods and hybrid imaging.

PMID- 30100944
TI  - Prevalence and Risk Factors of Atypical Femoral Fracture Bone Scintigraphic
      Feature in Patients Experiencing Bisphosphonate-Related Osteonecrosis of the Jaw.
AB  - Purpose: Bisphosphonate (BP) is the first-line therapy for the management of
      osteoporosis. BP-related osteonecrosis of the jaw (BRONJ) and atypical femoral
      fracture (AFF) are increasingly common comorbidities in patients with
      osteoporosis under long-term BP treatment. The aim of this study was to evaluate
      the incidence and risk factors for AFF features on bone scintigraphy in patients
      with BRONJ. Methods: Among total of 373 BRONJ patients treated between September
      2005 and July 2014, 237 (220 women, 17 men; median age 73 years) who underwent
      three-phase bone scintigraphy were enrolled for this retrospective study. AFF
      features on bone scintigraphy and the related clinical factors were assessed.
      Results: Among 237 patients with BRONJ, 11 (4.6%) showed AFF features on bone
      scintigraphy. BP medication duration (p = 0.049) correlated significantly with
      AFF features on bone scintigraphy in patients with BRONJ. BP intake duration of
      34 months was the cutoff value for predicting the presence of AFF features on
      bone scintigraphy. Among the patients with BRONJ, all those with AFF features on
      bone scintigraphy were female patients with osteoporosis who were on oral BP
      medication; however, these factors were not significantly different along with
      AFF features on bone scintigraphy. Conclusion: The incidence of AFF features on
      bone scintigraphy was relatively high in patients with BRONJ. A careful
      observation of patients presenting with the AFF features on bone scintigraphy may
      be needed, particularly for female BRONJ patients with osteoporosis who have been
      on BP medication for over 34 months.

PMID- 30100945
TI  - Bone and Calcified Soft Tissue Metastases of Medullary Thyroid Carcinoma Better
      Characterized on 18F-Fluoride PET/CT than on 68Ga-Dotatate PET/CT.
AB  - Herein, we report a case of a 19-year-old man with multiple endocrine neoplasia
      type 2B (MEN2B) and medullary thyroid carcinoma (MTC) diagnosed when he was 12
      years of age. The patient had previously undergone total thyroidectomy, cervical
      radiotherapy, and chemotherapy. He progressed with known bone, pulmonary, and
      lymph node metastases and was scanned with 18F-fluoride (18F-NaF) and 68Ga
      dotatate whole-body positron emission tomography/computed tomography (PET/CT) for
      metastatic disease monitoring. We found that the MTC bone metastases and soft
      tissue calcified metastases were better characterized on 18F-NaF PET/CT than on
      68Ga-dotatate PET/CT. This case illustrates that the 18F-NaF PET/CT could be
      helpful not only to the detection of bone metastases but also to the detection of
      calcified soft tissue metastases in patients with MTC.

PMID- 30100946
TI  - The Power of Analogies for Imagining and Governing Emerging Technologies.
AB  - The emergence of new technologies regularly involves comparisons with previous
      innovations. For instance, analogies with asbestos and genetically modified
      organisms have played a crucial role in the early societal debate about
      nanotechnology. This article explores the power of analogies in such debates and
      how they could be effectively and responsibly employed for imagining and
      governing emerging technologies in general and nanotechnology in particular.
      First, the concept of analogical imagination is developed to capture the
      explorative and anticipatory potential of analogies. Yet analogies do not simply
      stimulate imagination, they also restrict it by framing emerging technologies in
      specific ways. Thus, second, the article argues that tracing the rhetorical and
      persuasive power of analogical arguments is essential for understanding how
      analogies are constructed to legitimise assessments, funding policies, and
      governance approaches. Third, the article addresses factors that account for the
      persuasiveness of analogies in debates about emerging technologies. The article
      concludes with reflections on how analogical imagination and an enhanced
      analogical sensibility for framing and persuasive effects can foster responsible
      research and innovation (RRI).

PMID- 30100947
TI  - Frame Reflection Lab: a Playful Method for Frame Reflection on Synthetic Biology.
AB  - Synthetic biology is an emerging technology that asks for inclusive reflection on
      how people frame the field. To unravel how we can facilitate such reflection,
      this study evaluates the Frame Reflection Lab (FRL). Building upon playfulness
      design principles, the FRL comprises a workshop with video-narratives and co
      creative group exercises. We studied how the FRL facilitated frame reflection by
      organizing workshops with various student groups. Analysis of 12 group
      conversations and 158 mini-exit surveys yielded patterns in first-order
      reflection (problem analysis and solution finding in reflection on the
      development of synthetic biology as a field) as well as patterns in second-order
      reflection (reflection on values and assumptions underlying the first-order
      reflection). Also patterns in participants' (re)framing of synthetic biology
      could be induced; participants' viewpoints converged to some extent, yet with
      openness to individual viewpoint differences. Although the FRL method fortified
      the reflection processes of participants, the narratives and the workshop's
      flexible format could inhibit the reflection too. Therefore, we advise designers
      of future frame reflection methods to apply stronger conversational facilitation
      and narratives of slightly mysterious yet identifiable narrators, in case e.g.
      video-narratives are created and used to scaffold the reflection process.
      Nevertheless, we argue that the use of a playful frame reflection method like the
      FRL could function well as (1) a step to precede more application-specific
      deliberation or decision-making on synthetic biology and as (2) a method for the
      collection of contemporary citizen viewpoints plus rationales underlying these,
      for the further (societally) responsible development of the emerging field.

PMID- 30100948
TI  - STATIC AND ROVING SENSOR DATA FUSION FOR SPATIO-TEMPORAL HAZARD MAPPING WITH
      APPLICATION TO OCCUPATIONAL EXPOSURE ASSESSMENT.
AB  - Rapid technological advances have drastically improved the data collection
      capacity in occupational exposure assessment. However, advanced statistical
      methods for analyzing such data and drawing proper inference remain limited. The
      objectives of this paper are (1) to provide new spatio-temporal methodology that
      combines data from both roving and static sensors for data processing and hazard
      mapping across space and over time in an indoor environment, and (2) to compare
      the new method with the current industry practice, demonstrating the distinct
      advantages of the new method and the impact on occupational hazard assessment and
      future policy making in environmental health as well as occupational health. A
      novel spatio-temporal model with a continuous index in both space and time is
      proposed, and a profile likelihood-based model fitting procedure is developed
      that allows fusion of the two types of data. To account for potential differences
      between the static and roving sensors, we extend the model to have nonhomogenous
      measurement error variances. Our methodology is applied to a case study conducted
      in an engine test facility, and dynamic hazard maps are drawn to show features in
      the data that would have been missed by existing approaches, but are captured by
      the new method.

PMID- 30100950
TI  - Correction Notice: Twitter as a Tool for Teaching and Communicating Microbiology:
      The #microMOOCSEM Initiative.
AB  - [This corrects the article on p. 492 in vol. 17, PMID: 28101285.].

PMID- 30100949
TI  - Dimension reduction and estimation in the secondary analysis of case-control
      studies.
AB  - Studying the relationship between covariates based on retrospective data is the
      main purpose of secondary analysis, an area of increasing interest. We examine
      the secondary analysis problem when multiple covariates are available, while only
      a regression mean model is specified. Despite the completely parametric modeling
      of the regression mean function, the case-control nature of the data requires
      special treatment and semi-parametric efficient estimation generates various
      nonparametric estimation problems with multivariate covariates. We devise a
      dimension reduction approach that fits with the specified primary and secondary
      models in the original problem setting, and use reweighting to adjust for the
      case-control nature of the data, even when the disease rate in the source
      population is unknown. The resulting estimator is both locally efficient and
      robust against the misspecification of the regression error distribution, which
      can be heteroscedastic as well as non-Gaussian. We demonstrate the advantage of
      our method over several existing methods, both analytically and numerically.

PMID- 30100951
TI  - Understanding Student Perceptions and Practices for Pre-Lecture Content Reading
      in the Genetics Classroom.
AB  - Many faculty members assign textbook readings prior to their traditional
      lectures. In this study, we assessed students' level of class preparedness and
      surveyed their textbook reading practices weekly along with entrance and exit
      surveys concerning their attitudes toward reading the textbook. We report that
      pre-lecture reading is a significant variable in explaining pre-lecture
      preparedness as well as exam scores. We also report the reasons participants
      cited for not reading more of the textbook. We hope this analysis will allow
      educators to have a better understanding of the level of pre-lecture reading that
      is occurring in a traditional lecture-style course and the impacts of pre-lecture
      reading on student success.

PMID- 30100952
TI  - Life Science Majors' Math-Biology Task Values Relate to Student Characteristics
      and Predict the Likelihood of Taking Quantitative Biology Courses.
AB  - Expectancy-value theory of achievement motivation predicts that students' task
      values, which include their interest in and enjoyment of a task, their
      perceptions of the usefulness of a task (utility value), and their perceptions of
      the costs of engaging in the task (e.g., extra effort, anxiety), influence their
      achievement and academic-related choices. Further, these task values are
      theorized to be informed by students' sociocultural background. Although biology
      students are often considered to be math-averse, there is little empirical
      evidence of students' values of mathematics in the context of biology (math
      biology task values). To fill this gap in knowledge, we sought to determine 1)
      life science majors' math-biology task values, 2) how math-biology task values
      differ according to students' sociocultural background, and 3) whether math
      biology task values predict students' likelihood of taking quantitative biology
      courses. We surveyed life science majors about their likelihood of choosing to
      take quantitative biology courses and their interest in using mathematics to
      understand biology, the utility value of mathematics for their life science
      career, and the cost of doing mathematics in biology courses. Students on average
      reported some cost associated with doing mathematics in biology; however, they
      also reported high utility value and were more interested in using mathematics to
      understand biology than previously believed. Women and first-generation students
      reported more negative math-biology task values than men and continuing
      generation students. Finally, students' math-biology task values predicted their
      likelihood of taking biomodeling and biostatistics courses. Instructional
      strategies promoting positive math-biology task values could be particularly
      beneficial for women and first-generation students, increasing the likelihood
      that students would choose to take advanced quantitative biology courses.

PMID- 30100953
TI  - HIV/AIDS: A Case-Based Learning Module for First-Year Medical Students.
AB  - In medical and healthcare-related education, case-based learning (CBL) is a
      teaching strategy that uses clinical cases to engage students in active learning
      using course concepts to solve important problems. Here we describe the design
      and implementation of a CBL module to teach first year medical students about the
      human immunodeficiency virus (HIV), acute retroviral syndrome, clinical
      progression to acquired immunodeficiency syndrome, HIV diagnostics, assays used
      to assess stage of disease and response to antiretroviral treatment, and highly
      active antiretroviral therapy. A team of basic science and clinical faculty in
      the disciplines of microbiology, immunology, infection prevention and control,
      clinical medicine, pharmacology, and medical ethics collaboratively designed the
      CBL module. The results of a questionnaire indicated that the students found the
      CBL case interesting, engaging, and a useful educational strategy for linking
      basic science concepts to important clinical problems. In our experience, the CBL
      promoted student synthesis of basic science concepts across disciplines and
      engaged learners in the application of basic science knowledge to address
      significant real-world clinical problems.

PMID- 30100954
TI  - Student-Centered Microbioassay Laboratory Activity Utilizing Bioluminescent
      Bacteria.
AB  - Student-centered teaching allows students to be actively engaged in hands-on,
      minds-on activities that emphasize creativity and collaboration, enabling them to
      ask questions and design their own investigations to real-world problems. One
      such problem is water contamination, which causes human health and environmental
      issues. However, chemical water quality testing for pollutants can be timely and
      expensive. In addition to chemical testing, researchers have developed assays
      using unicellular organisms to determine which pollutants are present and in what
      concentrations. In this three-hour laboratory activity, high school students and
      undergraduate biology or microbiology students work in pairs to help a fictional
      company develop a water quality microbioassay. Students design their own
      laboratory protocols to test the reaction of a bioluminescent bacterial species
      (i.e., Photobacterium phosphoreum or Aliivibrio fischeri ) to exposure of common
      aquatic pollutants such as fertilizer, household cleaners, and motor oil. During
      this laboratory activity, students apply previously learned components of
      experimental design, including positive and negative controls, constants, and
      experimental groups. In addition, students gain experience writing a scientific
      explanation for a recommendation regarding the bioluminescent bacteria's
      suitability in a bioassay. Pre- and post-evaluation data revealed that students
      were successful in achieving the activity's objectives as well as in designing
      their investigations and writing their protocols using scaffolds within the
      lesson.

PMID- 30100955
TI  - Neglected intraocular wooden foreign bodies.

PMID- 30100956
TI  - [The superficial circumscribed lymphangioma of the tongue].
AB  - Superficial circumscribed lymphangiomas are predominantly benign lesions occuring
      in the cervicofacial area. These malformations of the lymphatic vessels are
      frequently diagnosed in children. We report the clinical case of lymphangioma of
      the tongue that occurred in an old man. The differential diagnosis was made
      primarily with Kaposi's disease, circumscribed angiokeratoma and metastases of a
      solid tumor. The patient had a biopsy that confirmed the diagnosis. The decision
      was abstention and supervision since the patient was not embarrassed.

PMID- 30100957
TI  - [Parotid tuberculosis: a forgotten diagnosis, about 2 cases and literature
      review].

PMID- 30100958
TI  - Prevalence of rifampicin resistance by automated Genexpert rifampicin assay in
      patients with pulmonary tuberculosis in Yenagoa, Nigeria.
AB  - Introduction: The diagnosis of tuberculosis and its treatment is challenging in
      resource - limited settings. The growth and speed of multi drug - resistant
      tuberculosis (MDR-TB) in high burden countries like Nigeria is a growing concern.
      This study is aimed at determining the prevalence of rifampicin resistance in
      sputum specimens of patients with pulmonary tuberculosis in Yenagoa, Nigeria.
      Methods: A descriptive survey of all consecutive sputum specimens of adults
      greater than 15 years of age that presented to the Tuberculosis Referral Hospital
      Laboratory were subjected to the automated Genexpert test between January and
      December 2016. Results: All 446 specimens were tested using the Genexpert
      automated system. 102 (22.9%) of the sputum specimens were positive for
      Mycobacterium tuberculosis, with 15 (14.7%) showing rifampicin resistance.
      Conclusion: There was significantly high prevalence of MDR-TB much higher than
      the World Health Organisation (WHO) prediction of 3.2 -5.4% for Nigeria.Pan
      African Medical Journal - ISSN: 1937- 8688 (www.panafrican-med
      journal.com)Published in partnership with the African Field Epidemiology Network
      (AFENET). (www.afenet.net)Pan African Medical Journal - ISSN: 1937- 8688
      (www.panafrican-med-journal.com)Published in partnership with the African Field
      Epidemiology Network (AFENET). (www.afenet.net).

PMID- 30100959
TI  - Hematological parameters of the blood count in a healthy population of pregnant
      women in the Northwest of Morocco (Tetouan-M'diq-Fnideq provinces).
AB  - Introduction: Numerous biological parameters are physiologically modified during
      normal pregnancy, in particular hematology. The knowledge of these modifications
      of the maternal body by biologists and clinicians allows the screening of
      possible anomalies. In Morocco, the reference values of the complete blood count
      test for pregnant woman are missing, as are those specific to different
      trimesters of pregnancy. The aim of this study is to look for the reference
      values for healthy pregnant women of the Northwest region of Morocco, to compare
      them to those of non-pregnant women (control) and to those of the literature.
      Methods: Blood samples were taken voluntarily from 3898 healthy pregnant women
      from 18 to 46 years old who presented themselves at the center of health Kalaa
      and at the service of gynecology obstetrics of the Provincial Hospital Center of
      M'diq (Morocco), for prenatal care. To establish the reference intervals of the
      CBC for non-pregnant women, a control group was constituted by 7035 healthy women
      from 18 to 50 years old selected according to the Moroccan law of blood donation.
      The CBC was measured on a Sysmex KX21N(r) analyzer. For each sample a systematic
      blood smear was done to determine the leukocyte differential. Results: A
      statistically significant difference between the pregnant women and control group
      was noted (p < 0.05) for all the hematological parameters: red blood cells,
      hematocrit, hemoglobin, mean corpuscular volume, mean corpuscular hemoglobin,
      mean corpuscular hemoglobin concentration, leukocytes, neutrophils, basophils,
      eosinophils, lymphocytes, monocytes, platelets and mean platelet volume. So, the
      comparison of the averages established between the first, second and third
      trimester of pregnancy showed the existence of a significant variation with
      regard to all the parameters of the CBC test looked for (p < 0.001). Conclusion:
      The present study provides additional baseline data for basic hematological
      parameters in healthy pregnant Moroccan women and concluded that pregnancy in
      women has the tendency to alter some hematological indices. For these reasons,
      there is an interest to take these modifications into account for optimal
      maternal and fetal medical care.

PMID- 30100960
TI  - ?
AB  - Chronic hydrocephalus associated with a tumor of the conus medullaris and/or of
      the cauda equina is extremely rare. We here report two cases of medullary tumor
      revealed by the triad: dementia, difficulty walking and urinary incontinence.
      Magnetic resonance imaging (MRI) of the cerebrospinal fluid showed communicating
      hydrocephalus and intradural spinal tumors at the level of the conus medullaris
      and of the cauda equina. Surgical resection of a benign schwannoma and of an
      ependymoma allowed the resolution of the clinical symptomatology due to
      hydrocephalus without implantation of ventricular shunt. A dozen cases of
      dementia and hydrocephalus associated to spinal tumor have been reported. A
      variety of approaches have been proposed to explain this association but the
      exact pathophysiology is not accurately known. 

PMID- 30100961
TI  - [Myositis ossificans circumscripta of the hip: about a case].
AB  - Myositis ossificans circumscripta (MOC) is a rare benign condition characterized
      by heterotopic ossification occurring in the soft tissues. We report the case of
      a 15-year old patient complaining of mixed hip pain. No trauma has been reported
      during the interview. The joint had inflammation appearance and a non-mobilizing
      swelling adhered to the deeper structure with parietal projection over the groin
      fold. Radiographs of the hip showed a thickening of the soft tissues of the hip
      and some periarticular calcifications with unclear appearance. Excisional biopsy
      of the calcifications was decided and performed. Diagnosis was confirmed by
      histological examination of the surgical specimen. At six months follow-up the
      patient was very satisfied with his functional results. Returning to school
      sports was authorized. The patient had successful outcome.

PMID- 30100963
TI  - [A special form of pancytopenia].
AB  - Primary hyperoxaluria is a rare disease whose incidence is estimated at less than
      1 cases/million inhabitants/year. This is a congenital abnormality of hepatic
      metabolism leading to an endogenous overproduction of oxalate with excess urinary
      excretion. We report the case of a 43-year-old patient, was followed to end-stage
      renal disease hemodialysis, consulting for anemic syndrome with mucocutaneous
      pallor. Laboratory tests found pancytopenia with aplastic anemia. Bone marrow was
      difficult to achieve, bringing medullary blood hyperdilue and uninterpretable .
      Radiographs showed a homogeneous splenomegaly and small dedifferentiated a kidney
      marrow biopsy was performed. Histological examination revealed a myelofibrosis
      and birefringent crystals in polarized light, diagnosis retained: spinal
      oxalosis.

PMID- 30100962
TI  - Treatment interventions for diarrhoea in HIV-infected and HIV-exposed children: a
      systematic review.
AB  - Introduction: Seventy percent of an estimated 10 million children less than five
      years of age in developing countries die each year of acute respiratory
      infections, diarrhoea, measles, malaria, malnutrition or a combination of these
      conditions. Children living with Human immunodeficiency virus (HIV) are at risk
      of diarrhoea because of drug interactions with antiretroviral therapy and bottle
      feeding. This may be aggravated by malnutrition and other infectious diseases
      which are frequent in children living with HIV. Objective: to evaluate treatment
      interventions for diarrhoea in HIV infected and exposed children. Methods: A
      comprehensive search was conducted on 02 June 2016 to identify relevant studies
      for inclusion. We included randomised controlled trials of HIV infected or
      exposed children under 15 years of age with diarrhoea. Two authors independently
      selected studies for inclusion, assessed risk of bias (RoB) and extracted data
      using a pre-designed data extraction form. Results: We included two studies
      (Amadi 2002 and Mda 2010) that each enrolled 50 participants. The RoB was
      assessed as low-risk for both included studies. There was no difference in
      clinical cure and all-cause mortality between nitazoxanide and placebo for
      cryptosporidial diarrhoea in Amadi 2002. In Mda 2010, there was a reduction in
      duration of hospitalisation in the micronutrient supplement group (P < 0.005)
      although there was no difference in all-cause mortality. Conclusion: There is low
      certainty evidence on the effectiveness of nitazoxanide for treating
      cryptosporidial diarrhoea and micronutrient supplementation in children with
      diarrhoea. Adequately powered trials are needed to assess micronutrients and
      nitazoxanide, as well as other interventions, for diarrhoea in HIV-infected and
      exposed children.

PMID- 30100964
TI  - Creation of the bone bank of the Rabat and Casablanca region in Morocco.
AB  - For a long time the use of bone grafting has demonstrated its interest in
      orthopedic surgery and traumatology. The autografts which are still very
      frequently used present various problems. On the one hand, it is necessary to
      find a correct mechanical quality and a sufficient quantity of bone. On the other
      hand, the graft removal lengthens the operative time and generally painful in
      postoperative. These disadvantages of autografts have led to the development of
      bone allografts. Indeed, the low immunogenic power of the bone, the good
      integration of the graft and the ease of bone preservation techniques make it
      possible to overcome the various problems posed by bone autografts. The
      increasing use of bone allografts has resulted in the need for a structure
      allowing the management of graft stocks. The purpose of this work is to
      demonstrate the mode of operation of a bone bank, whose conservation activity is
      limited to the femoral heads treated by cryopreservation and without secondary
      sterilization process. The bank collaborates with all orthopedic surgeons in the
      Rabat and Casablanca city at first and then with all orthopedic surgeons in
      Morocco. It provides allografts in quality and safety.

PMID- 30100965
TI  - [Meningeal melanocytoma: aggressive evolution of a benign tumor: about 2 cases].
AB  - Meningeal melanocytomas are rare pigmented tumors affecting the central nervous
      system and developing in the cerebrospinal leptomeninges. We report two cases of
      meningeal melanocytomas showing very marked disparity in their evolution: a very
      long-term development of meningocerebral lesion, with malignant transformation
      resulting in the death of the first patient after 32 years and intramedullary
      ectopic location with very fast massive meningeal diffusion in the second
      patient. These two cases show the uncertain evolutive profile of meningeal
      melanocytomas. These lesions may become aggressive with poor prognosis despite an
      intensive therapeutic strategy.

PMID- 30100966
TI  - [Bilateral adrenal tuberculosis: about a case].
AB  - Isolated adrenal tuberculosis accounts for less than 2% of adrenal
      incidentalomas. This is the most frequent infectious cause of adrenal
      insufficiencies. We report the case of a 53-year old patient with no previous
      medical history presenting with adrenal insufficiency with slow progression over
      six months. Physical examination didn't show any mass or hepatosplenomegaly.
      Blood pressure was 120/60 mmHg. Laboratory tests didn't show inflammatory
      syndrome. LDH level was normal. CT scan showed bilateral hypertrophy of the
      adrenal glands characterized by calcifications. Intradermo tuberculin reaction
      was positive at 25mm. The analyses to detect Koch's bacillus in the sputum and in
      the urine were negative. Quantiferon(r) test was positive. Trial antibacillar
      treatment was started with clinical improvement and 5kg weight gain in 12 months.
      Hormonal assays were low.

PMID- 30100967
TI  - [An unusual cause of alopecia on the scalp].
AB  - Alopecia is defined as a congenital or temporary absence of hair or even as total
      or partial hair loss. Clinical manifestation is more marked on the scalp and it
      is more common in men than in women. Nevertheless, a set of extrinsic factors may
      be responsible for scarring alopecia of the scalp, including tumors, infections
      or even loss of substance secondary to thermal burns. On the basis of these
      illustrations, we here report three cases of patients with scarring alopecia of
      the scalp secondary to so-called "atypical" causes. The first case (A) is that of
      a 6-year-old child presenting with alopecia on the right parietal scalp. In-depth
      interview with his mother allowed to discover the cause of the loss of substance:
      cutaneous necrosis following laborious delivery by vacuum extraction. The second
      illustration (B) shows the case of a 40-year-old woman seen in consultation for
      cutaneous necrosis of the occipital scalp secondary to chemical burn. The patient
      reported the application of a chemical product in order to fix hairstyle.
      Finally, the third case (C) is that of a 27-year old patient followed-up for
      bilateral frontoparietal alopecia secondary to the application of poisonous plant
      having, according to her beliefs, nourishing virtues for the hair.

PMID- 30100968
TI  - Necrobiosis lipoidica: a rare complication of diabetes.

PMID- 30100969
TI  - Psychosocial predictors of consistent condom use among migrant road construction
      workers in the Southwest Region of Cameroon using the Health Belief Model.
AB  - Introduction: A significant proportion of road construction workers are migrants
      and prone to HIV infection. This study investigated the psychosocial predictors
      of consistent condom use among migrant road construction workers in the South
      west region of Cameroon using the Health Belief Model (HBM) as the theoretical
      framework. Methods: A cross-sectional survey of a stratified sample of 254 road
      construction workers was conducted at construction sites along the Kumba-Mamfe
      road in the South-west region of Cameroon in December 2015. Data were collected
      using a pretested structured questionnaire and binomial logistic regression was
      performed to test the strength of association between the independent and the
      dependent variables using SPSS version 20 at the level 0.05. Results: Only 67
      (43.5%) reported consistent condom use. Perception of risk of contracting HIV was
      also low, 109 (42.9%). None of the constructs of the HBM was significantly
      associated with consistent condom use. However, perception that road construction
      workers are prone to HIV (perceived susceptibility) was associated with an
      increased likelihood of using condom consistently, OR = 2.1 (95% CI 0.72-6.12, p
      = 0.17); perception that consistent condom use could prevent HIV transmission
      (perceived benefit) was associated with an increased likelihood of using it
      consistently, OR = 1.9 (95% CI 0.74-4.80, p = 0.18); perception by workers that
      they can refuse sex with their partners if they refuse to use condoms (perceived
      self-efficacy) was associated with an increased likelihood of using condoms
      consistently, OR = 1.5 (95% CI 0.62-3.53, p = 0.38). However, the perception that
      condom reduces sexual pleasure (perceived barriers) was associated with a reduced
      likelihood of using it consistently, OR = 0.84 (95% CI 0.35-2.01, p = 0.698).
      Conclusion: There were no significant associations between the psycho-social
      constructs of the HBM and consistent condom use. Therefore, interventions to
      increase the perception of risk of contracting HIV, which is assumed to be the
      immediate antecedent of consistent condom use is highly recommended.

PMID- 30100970
TI  - Monteggia fracture with unreducable anterior dislocation of the radial head and a
      lesion of the external collateral ligament of the elbow.
AB  - Monteggia described a fracture of the proximal third of the ulna with anterior
      dislocation of the radial head from both the proximal radioulnar and
      radiocapitellar joints. The key treatment principle in Monteggia fractures is
      stable anatomic alignment of the ulna. We present an uncommon case of a Monteggia
      fracture-dislocation with an unreducable anterior dislocation of the radial head
      and associated with a lesion of the lateral collateral ligament of the elbow. The
      patient in our report had a successful clinical outcome and functional range of
      motion after rigid fixation of the ulnar shaft fracture and exploration of the
      elbow joint, reduction of the radial head and repair of the lateral collateral
      ligament. This case is unusual because of the association of a complete tear of
      the external collateral ligament of the elbow.

PMID- 30100972
TI  - Total bilateral urine collecting system duplication.

PMID- 30100971
TI  - Epidemiology of snake bites in selected areas of Kenya.
AB  - Introduction: Snake bites are a silent public health problem in Kenya. Previous
      studies on snake bites in the country have mainly focused on identifying
      offending snake species, assessing the severity of envenomation and testing the
      efficacy of antivenom. Factors associated with snake bites in the country are yet
      to be fully understood. The aim of this work was to determine pharmaco
      epidemiological factors associated with snake bites in areas of Kenya where
      incidence, severity and species responsible for snake bites have been reported.
      Methods: Kakamega provincial hospital, Kabarnet, Kapenguria and, Makueni district
      hospitals were selected as study sites based on previous findings on incidence,
      severity and species responsible for snake bites in catchment areas of these
      hospitals. Persistent newspaper reports of snake bites in these areas and
      distribution of snakes in Kenya were also considered. Cases of snake bites
      reported between 2007-2009 were retrospectively reviewed and data on incidence,
      age, site of the bites, time of bite and antivenom use was collected. Results:
      176 bites were captured, 91 of which occurred in 2009. Individual incidence was
      between 2.7/100,000/year and 6.7/100,000/year. Bites peaked in the 1-15 year age
      group while 132/176 bites were in the lower limb area and 49/176 victims received
      antivenom. Most bites occurred during the dry season, in the bush and in the
      evening. Overall mortality was 2.27%. Conclusion: There is a need to sensitize
      the Kenyan public and healthcare personnel on preventive measures, first aid and
      treatment of snake bites.

PMID- 30100973
TI  - An antibiotic audit of the surgical department at a rural hospital in Western
      Kenya.
AB  - Introduction: Antibiotics are one of the most commonly prescribed medications in
      hospitalized patients, with up to half of prescriptions being irrational. This
      study aimed to assess the quality of antibiotic use among surgical inpatients at
      our institution. Methods: A one year (January 1-December 31, 2015) retrospective
      chart review on antibiotic use for patients admitted to the surgical department
      at AIC Litein Hospital, a faith based non-governmental health institution in
      Western Kenya, was conducted. Data were collected from medical and nursing
      patient charts with a standardized questionnaire. The criteria applied to assess
      inappropriate antibiotic use focused on the choice, duration and indication of
      the antibiotics prescribed. Results: A total of 394 cases were evaluated, with a
      mean age of 44.8 years and a mean duration of hospitalization of 7.2 days.
      Antibiotics were initiated either for prophylaxis (205, 56.3%) or treatment (159,
      43.7%) for a mean duration of 6 days (range 1-37). The predominant route of
      administration was intravenous (332, 91.2%). Most antibiotics started at
      admission were continued till discharge and the duration of antibiotics was
      indicated in only 11% of the treatment sheets. At discharge, 321 (81.4%) cases
      had antibiotics prescribed for a mean duration of 5.7 days (range 1-60).
      Inappropriate prescriptions were noted in 45.4% of prophylactic antibiotics,
      33.4% treatment antibiotics and 52.6% of discharge antibiotics. The most common
      reason for inappropriate antibiotic use during hospitalization was inappropriate
      duration (45.9%). Conclusion: Proper documentation, daily antibiotic review and
      preparation of a local antibiotic policy guideline could help improve the
      appropriate use of antibiotics.

PMID- 30100976
TI  - [Bilateral persistent pupillary membrane and high myopia].
AB  - After birth, remnants of pupillary membrane which constitute the vascular supply
      to the crystalline lens can persist. These are contiguous to the iris collarette
      causing possible deprivation amblyopia by obstructing the pupillary area. We here
      report the case of a 4-year-old child, born to consanguineous parents, presenting
      with bilateral persistent pupillary membrane associated with high myopia.
      Clinical examination showed bilateral remnants of pupillary membrane, intact iris
      sphincter and diffuse chorioretinal atrophy in the fundus of eye . Visual acuity
      was difficult to assess. On the other hand, refraction test showed high myopia RE
      -10.75 (-3.25, 29 degrees ) LE -10 (-0.75, 180 degrees ). Treatment of bilateral
      persistent pupillary membrane is based on mydriatic agents, surgical excision or
      laser destruction. We opted for the use of mydriatic agents with total optical
      correction and amblyopia treatment.

PMID- 30100974
TI  - Predictors of low birth weight and 24-hour perinatal outcomes at Muhimbili
      National Hospital in Dar es Salaam, Tanzania: a five-year retrospective analysis
      of obstetric records.
AB  - Introduction: The global prevalence of low birth weight (LBW) is 16%,
      representing more than 20 million infants worldwide, of which 96% are born in low
      income countries. This study aimed to determine the prevalence, predictors and
      perinatal outcomes of LBW newborns. Methods: We conducted a retrospective
      analysis of data obtained from the hospital's obstetric and neonatal database.
      Descriptive statistics and multivariate logistic regression were performed with
      95% confidence intervals (CI). Results: The prevalence of LBW was 21% (n = 8,011)
      and two-thirds of these were delivered at term. Seven percent of newborns were
      stillbirths and 2% died within 24hrs after birth. Logistic regression revealed
      that primigravida and grand multiparity were associated with LBW (OR: 1.25,
      95%CI: 1.15-1.37; and OR: 1.21, 95%CI: 1.01-1.25, respectively). Having <4
      antenatal care (ANC) visits was associated with increased odds of LBW (OR: 1.74,
      95%CI: 1.59-1.87). Regression models revealed an independent association between
      LBW and increased odds of stillbirths (OR = 7.20, 95%CI 6.71-7.90), low Apgar
      score (OR = 3.42, 95%CI: 3.12-3.76) and early neonatal deaths (OR = 1.82, 95%CI:
      1.51-2.19). Conclusion: The prevalence of LBW was high and was associated with
      extreme maternal age groups, grand multiparity, low maternal education, low
      number of ANC visits and obstetrics risks factors and complications. Both LBW and
      prematurity were independently associated with poor perinatal outcome. Future
      interventions should focus on improving the quality of ANC and integrating
      peripartum emergency obstetric and neonatal care.

PMID- 30100977
TI  - Non-referral of potential organ donors in South Africa: insights, challenges and
      ethical dilemmas.
AB  - Traditionally, minimal potential organ donor referrals emanate from general
      medicine departments. We use a clinical vignette to draw attention to challenges
      related to referral of potential organ donors from general internal medicine
      departments. In addition, we provide potential solutions to overcome challenges
      and reflect on the ethical issues of non-referral of potential organ donors. It
      is hoped that this paper will increase the awareness of organ donation in the
      medical fraternity in Africa and thus mitigate critical shortages of organs for
      transplantation.

PMID- 30100975
TI  - [Psychological distress in medical and paramedical personnel in anesthesia and
      intensive care].
AB  - Anesthesia and intensive care medicine is considered one of the specialties
      involving more professional stress (PS). On this basis, our study aimed to assess
      the level of anxiety and PS in the personnel in anesthesia and intensive care and
      to identify the associated factors. We conducted a cross-sectional, descriptive
      and analytical study including 54 participants (38 technicians and 16 residents)
      working in the Departments of Anesthesia and Intensive Care at Habib Bourguiba
      and Hedi Chaker University Hospitals, Sfax, Tunisia. PS assessment was performed
      using the Karasek questionnaire. The Hamilton Anxiety Rating Scale (HARS) was
      used to measure the severity of anxiety symptoms. According to the Karasek
      questionnaire, the average decision latitude score was 69, the average
      psychological demand score was 23.9 and the average social support score was
      19.6. According to this questionnaire, 40.7% of personnel was stressed and 38.9%
      was in isostrain condition. Average HARS score was 17.8, average psychic anxiety
      score was 8.7 and average somatic anxiety score was 9, with a significant
      difference between the medical and paramedical personnel. Severe to very severe
      anxiety was recorded in 25.9% of cases. HARS score was correlated to female
      gender (p=0.017) and to psychiatric histories (p=0.003). This study highlights
      that medical and paramedical personnel in anesthesia and intensive care is
      exposed to a significant risk of PS. Changes in working environment as well as
      learning professional stress management techniques should be proposed.

PMID- 30100978
TI  - A comparison of five international clinical trial registers with the South
      African register for access to information and usability.
AB  - Introduction: in November, 2005, the South African (SA) National Department of
      Health (NDoH) mandated that, as from the 1st December, 2005, all new clinical
      trials to be conducted in the country must be registered on the South African
      National Clinical Trials Register (SANCTR). The objective was to compare access
      to the information contained in and the usability of the SANCTR with five other
      international on-line clinical trials registers. Methods: Access to SANCTR was
      determined through the use of three search engines using the keywords "South
      African Clinical Trials." Five high-profile international registers were
      identified and accessed for comparative purposes. Each register was investigated
      for information on trials conducted in South Africa using a standardised data
      extraction form which listed 24 data items. The usability of the various on-line
      registers was determined through a self-administered questionnaire adapted from
      the five key usability factors previously defined in literature. Heuristic
      evaluation was carried out with 10 'experts' (Pharmacy staff and postgraduate
      students at Sefako Makgatho Health Sciences University (SMU)). Data generated
      from the heuristic evaluation were analysed using descriptive statistics,
      univariate and multivariate analyses. Results: The SANCTR website had the highest
      ranking for access amongst the registers in all three selected search-engines
      after an internet search using the keywords "South African Clinical Trials". The
      total number of clinical trials registered varied among the registers. The WHO's
      International Clinical Trials Registry Platform (ICTRP) recorded 2 599 trials
      carried out in South Africa, with 2 260 registered in the ClinicalTrials.gov
      register, 2 196 in the SANCTR and 978, 149 and 174 in the European Union (EU),
      International Standard Randomised Controlled Trial Number (ISRCTN) and Pan
      African Clinical Trials (PACTR) registers respectively. The websites
      ClinicalTrials.gov and ISRCTN provided greater overall information per clinical
      trial registered and provided information on all 24 clinical trials data items.
      The PACTR had information on 23 of the 24 data items. The WHO and EU registers
      each contained 19 data items. The SANCTR provided the least information, only 11
      data items. The heuristic evaluation identified ClinicalTrials.gov as the 'best'
      site, while the PACTR had the lowest rating for layout and design. The EU
      register and SANCTR were the least easily navigable. The respondents had the
      least satisfaction while using the 'Search' option in the SANCTR. Users also
      reported the SANCTR and the PACTR had the lowest overall user-friendliness.
      Conclusion: The fact that the SANCTR contains less information on SA clinical
      trials than other registers and is the least user-friendly warrants utmost
      attention. The study puts forward a case to the regulatory authority (currently
      the Medicines Control Council) as it takes on a new structure and working
      arrangements as the South African Health Products Regulatory Authority to
      optimise the SANCTR to be more user-friendly and contain more complete
      information on clinical trials conducted in SA.

PMID- 30100979
TI  - Detection and analysis of drug-drug interactions among hospitalized cardiac
      patients in the Mohammed V Military Teaching Hospital in Morocco.
AB  - Introduction: Drug-drug interactions (DDIs) are defined as two or more drugs
      interacting in such a manner that the effectiveness or toxicity of one or more
      drugs is altered. Patients with cardiovascular disorders are at higher risk for
      DDIs because of the types and number of drugs they receive. The aim of the
      present study was to assess the prevalence of DDIs in patients admitted to the
      cardiology department of a hospital in Morocco. Methods: A prospective
      observational study from June 2016 to September 2016 was carried out in the
      cardiology department of a hospital in Morocco. Those patients who were taking at
      least two drugs and had a hospital stay of at least 48 hours were included in the
      study. The medications of the patients were analysed for possible interactions.
      All the prescriptions of the study population were screened for drug-drug
      interactions using a computerized DDI database system (Theriaque(r)). Results:
      During the study period, 138 patients were included; 360 interactions were
      detected among 94 patients, with an average number of drugs taken of 5.2. The
      prevalence of DDIs was estimated at 68.11%, the most common of which concerned
      Kardegic/Plavix (12.22%), Kardegic/Heparin (8.33%), and Lasilix/Spironolactone
      (5.83%). Among the 726 prescribed drugs, (372 [51.24%]) were drugs of the
      cardiovascular system, followed by blood and hematopoietic organ drugs (288
      [39.67%]) according to the Anatomical Therapeutic Chemical Classification codes.
      These interactions were categorized on the basis of level of severity:
      interactions with major severity accounted for 11.11% (40) of the total DDIs
      while those with moderate and minor severity accounted for 37.22% (134) and
      51.66% (186), respectively. Conclusion: This study reports the prevalence of DDIs
      in patients admitted to the cardiology department of a hospital in Morocco. This
      study shows that DDIs are frequent among hospitalized cardiac patients and
      highlights the need to screen prescriptions of cardiovascular patients for
      possible DDIs, as this helps in their detection and prevention.Pan African
      Medical Journal - ISSN: 1937- 8688 (www.panafrican-med-journal.com)Published in
      partnership with the African Field Epidemiology Network (AFENET).
      (www.afenet.net)Pan African Medical Journal - ISSN: 1937- 8688 (www.panafrican
      med-journal.com)Published in partnership with the African Field Epidemiology
      Network (AFENET). (www.afenet.net).

PMID- 30100980
TI  - First documented evidence of dengue and malaria co-infection in children
      attending two health centers in Yaounde, Cameroon.
AB  - To date, only a few cases of malaria and dengue co-infections have been reported
      around the world. We describe for the first time in Cameroon, concurrent
      infections among children (2 to 10 years) in two health centers of Yaounde. The
      two dengue strains isolated in Cameroon clustered with the Asian II genotype.
      Although acute concurrent infections were benign, special attention should be
      given to malaria and dengue co-infection in order to prevent possible severe
      cases.

PMID- 30100981
TI  - Treatment and rehabilitation outcomes of children affected with nodding syndrome
      in Northern Uganda: a descriptive case series.
AB  - Introduction: Nodding Syndrome (NS) is a neurological disorder affecting children
      5-15 years at onset in East Africa. A major criterion for diagnosis is atonic
      seizure with dorso-ventral "nodding" of the head. Comorbidities include
      psychological and behavioral abnormalities, malnutrition, cognitive decline,
      school dropout and other seizure types. We aimed to describe the presentations
      and rehabilitation outcomes of NS children at Hope for HumaNs (HfH) centre in
      Gulu from September 2012 to October 2013. Methods: Data was obtained from a
      retrospective review of 32 NS children's medical records at HfH center. Ethical
      approval was obtained from Gulu University IRB. Data analysis was conducted using
      WHO AnthroPlus, SPSS and Excel software. Results: Growth statistics showed steady
      improvement over time using local nutrition and multivitamin supplementation.
      Severe and moderate stunting was reduced from a combined total of 54.8% to 7.7%
      and 12.8% respectively. Severe and moderate wasting was reduced from 29.1% to
      2.6% and 5.1% respectively. Three groups of NS children were identified and
      compared in the review; Low seizure occurrence averaging <2 seizures/month
      (28.1%); Moderate averaging 2-4 seizures/month (34.4%) and High averaging >4
      seizures/month (37.5%). Conclusion: NS is a neurological disorder of unknown
      etiology. Treatment with regular high quality local nutrition, multivitamin
      supplementation, anti-seizures, regular follow up and illness prevention;
      children's seizures can be reduced or stopped completely. The debilitating
      malnutrition and stunting of NS children in Uganda could be partially independent
      of the syndrome but attributable to poor nutrition. NS as observed is not
      "invariably fatal" but rather a treatable neurological disorder.

PMID- 30100982
TI  - [Turrett's exostoses: about 35 casesk].
AB  - We conducted a retrospective study of 35 patients with subungual exostosis of the
      hallux, also known as Turrett's exostosis, in the Department of Orthopedics and
      Traumatology at the Senior Military Hospital of Instruction of Tunis over the
      period between 1995 and 2015. We here summarize the outcomes of patients treated
      for this disease. The average age of patients was 29 years, with a sex ratio of
      1.7. The median consultation time was six months. This delay in consultation was
      caused by a diagnostic error due to clinical picture resemblance with ingrown
      nail. Diagnosis was always confirmed by frontal and profile X-ray of the involved
      hallux. Treatment was based on total resection of the exostosis either through
      large ungual window or by latero-ungual approach. Anatomo-pathological
      examination was performed systematically. It allowed to confirm the benignity of
      the disease in all cases. All patients recovered and returned to their previous
      activity, on average, in 2 months. No patient had a recurrence.

PMID- 30100983
TI  - Does rapamycin slow down time?

PMID- 30100984
TI  - Galphai3 signaling is associated with sexual dimorphic expression of the clock
      controlled output gene Dbp in murine liver.
AB  - The albumin D-box binding protein (DBP) is a member of the PAR bZip (proline and
      acidic amino acid-rich basic leucine zipper) transcription factor family and
      functions as important regulator of circadian core and output gene expression.
      Gene expression of DBP itself is under the control of E-box-dependent binding by
      the Bmal1-Clock heterodimer and CRE-dependent binding by the cAMP responsive
      element binding protein (CREB). However, the signaling mechanism mediating CREB
      dependent regulation of DBP expression in the peripheral clock remains elusive.
      In this study, we examined the role of the GPCR (G-protein-coupled
      receptor)/Galphai3 (Galphai3) controlled cAMP-CREB signaling pathway in the
      regulation of hepatic expression of core clock and clock-regulated genes,
      including Dbp. Analysis of circadian gene expression revealed that rhythmicity of
      hepatic transcript levels of the majority of core clock (including Per1) and
      clock-regulated genes were not affected by Galphai3 deficiency. Consistently, the
      period length of primary Galphai3 deficient tail fibroblasts expressing a Bmal1
      Luciferase reporter was not affected. Interestingly, however, Galphai3 deficient
      female but not male mice showed a tendentiously increased activation of CREB
      (nuclear pSer133-CREB) accompanied by an advanced peak in Dbp gene expression and
      elevated mRNA levels of the cytochrome P450 family member Cyp3a11, a target gene
      of DBP. Accordingly, selective inhibition of CREB led to a strongly decreased
      expression of DBP and CYP3A4 (human Cyp3a11 homologue) in HepG2 liver cells. In
      summary, our data suggest that the Galphai3-pCREB signalling pathway functions as
      a regulator of sexual-dimorphic expression of DBP and its xenobiotic target
      enzymes Cyp3a11/CYP3A4.

PMID- 30100985
TI  - High-throughput sequencing of murine immunoglobulin heavy chain repertoires using
      single side unique molecular identifiers on an Ion Torrent PGM.
AB  - With the advent of high-throughput sequencing (HTS), profiling immunoglobulin
      (IG) repertoires has become an essential part of immunological research. Advances
      in sequencing technology enable the IonTorrent Personal Genome Machine (PGM) to
      cover the full-length of IG mRNA transcripts. Nucleotide insertions and deletions
      (indels) are the dominant errors of the PGM sequencing platform and can
      critically influence IG repertoire assessments. Here, we present a PGM-tailored
      IG repertoire sequencing approach combining error correction through unique
      molecular identifier (UID) barcoding and indel detection through ImMunoGeneTics
      (IMGT), the most commonly used sequence alignment database for IG sequences.
      Using artificially falsified sequences for benchmarking, we found that IMGT's
      underlying algorithms efficiently detect 98% of the introduced indels. Undetected
      indels are either located at the end of the sequences or produce masked
      frameshifts with an insertion and deletion in close proximity. The complementary
      determining regions 3 (CDR3s) are returned correct for up to 3 insertions or 3
      deletions through conservative culling. We further show, that our PGM-tailored
      unique molecular identifiers result in highly accurate HTS data if combined with
      the presented processing strategy. In this regard, considering sequences with at
      least two copies from datasets with UID families of minimum 3 reads result in
      correct sequences with over 99% confidence. Finally, we show that the protocol
      can readily be used to generate homogenous datasets for bulk sequencing of murine
      bone marrow samples. Taken together, this approach will help to establish
      benchtop-scale sequencing of IG heavy chain transcripts in the field of IG
      repertoire research.

PMID- 30100986
TI  - Lamp2 inhibits epithelial-mesenchymal transition by suppressing Snail expression
      in HCC.
AB  - Lysosomal associated membrane protein 2 (Lamp2) influences a broad range of
      physiological and pathological processes. However, little is known about the role
      of Lamp2 in hepatocellular carcinoma (HCC) metastasis. This study found that
      Lamp2 expression was significantly lower in HCC tissues than in adjacent nontumor
      tissues (ANTs), and its expression level correlated with HCC metastasis. Low
      Lamp2 expression was significantly correlated with the AFP serum level (> 20
      ng/Ml, P = 0.024), capsular formation (absent, P = 0.024), and microvascular
      invasion (present, P < 0.001), and low expression of Lamp2 indicated a poor
      prognosis in HCC. LowLamp2 expression was an independent and significant risk
      factor for recurrence-free survival (RFS; P < 0.001) and overall survival (OS; P
      < 0.001) in HCC. In this study, we demonstrated that Lamp2 overexpression
      inhibited cell motility and invasiveness in vitro and inhibited lung metastasis
      in vivo. In addition, Lamp2 could reverse the EMT program. Lamp2 silencing by
      siRNA in HCC cell lines enhanced the expression of mesenchymal markers and
      decreased the expression of epithelial markers. Consistent with these findings,
      Lamp2 overexpression had the opposite effects. Mechanistically, we found that
      Lamp2 could suppress Snail expression, upregulate E-cadherin, and inhibit HCC
      cell epithelial-mesenchymal transition (EMT).Together, these findings suggest
      that Lamp2 attenuates EMT by suppressing Snail expression in HCC.

PMID- 30100987
TI  - Transcriptome profiling of anti-mullerian hormone treated preantral/small antral
      mouse ovary follicles.
AB  - The predisposition for the initiation of folliculogenesis in mammals including
      humans is programmed to start at fetal life and continues until reproductive
      capacity. The follicles grow from a pool of primordial follicles which retain the
      major functions in the entire reproductive life of a female. Anti-mullerian
      hormone (AMH), a glycoprotein belonging to the transforming growth factor-beta
      family, has an inhibitory effect on ovarian follicle development. The key
      regulatory target genes in primordial follicle development are of paramount
      importance in reproductive biology of female. A systems biology method was used
      to find regulatory genes performing critical role in primordial follicle
      development. A complete in-depth bioinformatics analysis was performed to
      investigate the changes in transcriptome of preantral to small antral mouse
      follicles treated for 12 h and 24 h with two different concentrations; 50 and 200
      ng/ml of AMH, and thereby identify candidate genes in time and concentration
      manner. Firstly, we found differentially expressed genes that were time and
      concentration dependent in response to AMH. The network analysis of these
      differentially expressed genes provided new candidate genes and pathways
      associated with inhibitory action of AMH on the primordial follicle development.
      To further emphasize the function of AMH, the key identified genes' protein
      protein docking was analyzed and found the intracellular and extracellular
      protein-protein interaction. This study elucidates one of the novel mechanisms of
      AMH involvement in inhibition of ovarian follicle development which may lead to
      prolong productive life in female.

PMID- 30100988
TI  - Non-invasive visualization of tumor infiltrating lymphocytes in patients with
      metastatic melanoma undergoing immune checkpoint inhibitor therapy: a pilot
      study.
AB  - Early in the course of immunotherapy there is frequently a transient enlargement
      of tumor masses (pseudo-progression) due to tumor infiltration by TILs. Current
      clinical imaging modalities are not able to distinguished pseudo-progression from
      true tumor progression. Thus, patients often remain on treatment 4-8 weeks longer
      to confirm disease progression. Nuclear medicine offers the possibility to image
      immune cells and potentially discriminate pseudo-progression and progression. We
      conducted a pilot study in patients with metastatic melanoma receiving ipilimumab
      (IPI) or pembrolizumab (PEMBRO) to assess safety and feasibility of SPECT/CT
      imaging with 99mTc- interleukin-2 (99mTc-HYNIC-IL2) to detect TILs and
      distinguish between true progression from pseudo- progression. Scans were
      performed prior to and after 12w treatment. After labelling,99mTc-HYNIC-IL2 was
      purified and diluted in 10 mL of 5% glucose with 0.1% human serum albumin. Of the
      5 patients (2 treated with IPI and 3 with PEMBRO) enrolled, two failed to
      complete the second scan as they discontinued IPI due grade 3 colitis (1 patient)
      or patient refusal after developing multiple toxicities attributed to IPI (1
      patient). Following the first scan, one patient reported to have a grade 1
      pruritus with grade 1 pain. No other toxicities attributed to the
      radiopharmaceutical infusion were reported. Metastatic lesions could be
      visualized by 99mTc-IL2 imaging and there was positive correlation between size
      and 99mTc-HYNIC-IL2 uptake, both before and after 12 weeks of therapy. The
      results of this pilot study demonstrate the safety and feasibility of 99mTc-IL2
      imaging and has led to a number of hypotheses to be tested in future studies.

PMID- 30100989
TI  - The DNA-polymorphism rs849142 is associated with skin toxicity induced by
      targeted anti-EGFR therapy using cetuximab.
AB  - Skin toxicity (ST) is a frequent adverse effect (AE) in anti-epidermal growth
      factor receptor (EGFR)-targeted treatment of metastatic colorectal cancer (mCRC)
      resulting in decreased quality of life and problems in clinical management. We
      wanted to identify biomarkers predicting ST in this setting and focused on 70 DNA
      polymorphisms associated with acne, the (immunoglobulin fragment crystallizable
      region) Fcgamma-receptor pathway, and systemic lupus erythematosus (SLE) applying
      next-generation-sequencing (NGS). For the analysis patients with mCRC treated
      with cetuximab were selected from the FIRE-3 study. A training group consisting
      of the phenotypes low (1) - and high-grade (3) ST (n = 16) and a validation group
      (n = 55) representing also the intermediate grade (2) were genotyped and
      investigated in a genotype-phenotype association analysis. The single nucleotide
      polymorphism (SNP) rs849142 significantly associated with ST in both the training
      (p < 0.01) and validation-group (p = 0.04). rs849142 is located in an intron of
      the juxtaposed with another zinc finger protein 1 (JAZF1) gene. Haplotype
      analysis demonstrated significant linkage disequilibrium of rs849142 with JAZF1.
      Thus, rs849142 might be a predictive biomarker for ST in anti-EGFR treated mCRC
      patients. Its value in the clinical management of AE has to be validated in
      larger cohorts.

PMID- 30100990
TI  - Autophagy processes are dependent on EGF receptor signaling.
AB  - Autophagy is a not well-understood conserved mechanism activated during
      nutritional deprivation in order to maintain cellular homeostasis. In the present
      study, we investigated the correlations between autophagy, apoptosis and the MAPK
      pathways in melanoma cell lines. We demonstrated that during starvation the EGF
      receptor mediated signaling activates many proteins involved in the MAPK pathway.
      Our data also suggest a previously unidentified link between the EGFR and Beclin
      1 in melanoma cell line. We demonstrated that, following starvation, EGFR binds
      and tyrosine-phosphorylates Beclin-1, suggesting that it may play a key
      inhibitory role in the early stage of starvation, possibly through the Beclin-1
      sequestration. Furthermore, EGFR releases Beclin-1 and allows initiating steps of
      the autophagic process. Interestingly enough, when the EGFR pathway was blocked
      by anti-EGF antibodies, immunoprecipitated Beclin-1 did not bind the phospho
      EGFR. In addition, an extended binding of p-Bcl2 either with Beclin-1 or with Bax
      was observed with a decreased activation of the stress-induced JNK kinase, thus
      avoiding the transduction pathways that activate autophagy and apoptosis,
      respectively. For this reason, we advance the hypothesis that the activation of
      the EGFR is a necessary event that allows the ignition and progression of the
      autophagic process, at least in melanoma cells.

PMID- 30100991
TI  - Prosopis juliflora (Sw.), DC induces apoptosis and cell cycle arrest in triple
      negative breast cancer cells: in vitro and in vivo investigations.
AB  - Plant originated drugs/formulations are extensively prescribed by the physicians
      as a complementary therapy for treating various human ailments including cancer.
      In this study Prosopis juliflora leaves methanol extract was prepared and exposed
      to human breast cancer cell lines i.e. MDA-MB-231 and MCF-7 and human
      keratinocytes HaCaT as a representative of normal cells. Initially, a series of
      in vitro experiments like cell proliferation, migration, colony formation, cell
      cycle arrest and inhibition of angiogenesis. After confirmation of the efficient
      and selective activity against triple negative breast cancer cell line, we
      further evaluated the possible mechanism of inducing cell death and experiments
      like detection of reactive oxygen species, caspases and poly (ADP-ribose)
      polymerase cleavage study and Annexin V assay were performed. We also evaluated
      in vivo anti tumorigenic activity of the P. juliflora leaves by using 4T1 cells
      (a triple negative mouse origin breast cancer cell line) and BALB/c xenograft
      mouse model. In vitro experiments revealed that methanol extract of Prosopis
      juliflora leaves possess impressive anti-breast cancer activity more specifically
      against triple negative breast cancer cells, while the in vivo studies
      demonstrated that P. juliflora leaves extract significantly suppressed the 4T1
      induced tumor growth. Present investigations clearly focus the significance of P.
      juliflora as an important resource for finding novel leads against triple
      negative breast cancer. The results may also act as a ready reference towards
      developing P. juliflora based formulation as an alternative and complementary
      medicine for the management of breast cancer.

PMID- 30100993
TI  - CAPER as a therapeutic target for triple negative breast cancer.
AB  - Breast cancers (BCas) that lack expression of the estrogen receptor (ER),
      progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)
      are referred to as triple negative breast cancers (TNBCs) and have the poorest
      clinical outcome. Once these aggressive tumors progress to distant organs, the
      median survival decreases to 12 months. With endocrine therapies being
      ineffective in this BCa subtype, highly toxic chemo- and radiation therapies are
      the only options. A better understanding of the functional role(s) of molecular
      targets contributing to TNBC progression could help in the design and development
      of new treatments that are more targeted with less toxicity. CAPER (Co-activator
      of AP-1 and ER) is a nuclear transcriptional co-activator that was recently
      involved in ER-positive BCa progression, however its role in hormone-independent
      cancers remains unknown. Our current report demonstrates that CAPER expression is
      upregulated in human TNBC specimens compared to normal breast tissue and that its
      selective downregulation through a lentiviral-mediated shRNA knockdown approach
      resulted in decreased cell numbers in MDA-MB-231 and BT549 TNBC cell lines
      without affecting the growth of non-tumorigenic cell line MCF-10A. Concordant
      with these observations, CAPER knockdown was also associated with a decrease in
      DNA repair proteins leading to a marked increase in apoptosis, through caspase
      3/7 activation without any changes in cell cycle. Collectively, we propose CAPER
      as an important signaling molecule in the development of TNBC linked to DNA
      repair mechanisms, which could lead to new therapeutic modalities for the
      treatment of this aggressive cancer.

PMID- 30100994
TI  - Risk factors for loco-regional recurrence in breast cancer patients: a
      retrospective study.
AB  - Background: Although fairly uncommon, loco-regional recurrence in breast cancer
      (BC) has major consequences for the patient. Several predictors for locoregional
      have been previously reported from large randomized clinical trials mainly from
      Europe & North America; data from other geographical areas are somewhat scarce.
      Here we performed a retrospective review of medical records in a single academic
      center in Chile, searching for predictors of breast tumor recurrence. Results:
      Median patient follow up was 61 months, 5 year overall survival (OS) rate was
      94.2% (95% CI 93-95.3). We found that 108 out of 2,754 (5.3%) patients had loco
      regional recurrence. The 2-year loco-regional control was 98% (95% CI 97.3-98.7)
      and 5-year was 94% (95% CI 92.6-95.4). Univariate analysis showed a correlation
      between recurrence and being <50 year-old, positive surgical margins, advanced
      stage, subtype, and presence of LVI and omission of adjuvant radiotherapy. Only
      the absence of adjuvant RT was predictor of locoregional recurrence in
      multivariable (p< 0.001). Conclusions: Our study population presents high local
      control of BC. Age, surgical margins, stage, molecular subtype and absence of
      adjuvant radiotherapy were associated with loco-regional recurrence. Prospective
      trials and long-term follow up are required in order to confirm these results.
      Materials and Methods: We analyzed medical records from 2,201 BC patients at the
      Pontificia Universidad Catolica de Chile from 1997 to 2016. Collected data
      included: age at diagnosis, tumor size, axillary involvement, molecular subtype,
      margin status, histological grade, lympho-vascular invasion (LVI) and ipsilateral
      recurrence.

PMID- 30100992
TI  - Doxorubicin-induced elevated oxidative stress and neurochemical alterations in
      brain and cognitive decline: protection by MESNA and insights into mechanisms of
      chemotherapy-induced cognitive impairment ("chemobrain").
AB  - Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a
      real and too common complication of cancer chemotherapy experienced by an ever
      growing number of cancer survivors. Previously, we reported that doxorubicin
      (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug,
      results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I)
      leading to tumor necrosis factor-alpha (TNF-alpha)-mediated oxidative stress in
      plasma and brain. We also reported that co-administration of the antioxidant
      drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein
      oxidation and subsequent TNF-alpha elevation in plasma. In this study, we
      measured oxidative stress in both brain and plasma of Dox-treated mice both with
      and without MESNA. MESNA ameliorated Dox-induced oxidative protein damage in
      plasma, confirming our prior studies, and in a new finding led to decreased
      oxidative stress in brain. This study also provides further functional and
      biochemical evidence of the mechanisms of CICI. Using novel object recognition
      (NOR), we demonstrated the Dox administration resulted in memory deficits, an
      effect that was rescued by MESNA. Using hydrogen magnetic resonance imaging
      spectroscopy (H1-MRS) techniques, we demonstrated that Dox administration led to
      a dramatic decrease in choline-containing compounds assessed by (Cho)/creatine
      ratios in the hippocampus in mice. To better elucidate a potential mechanism for
      this MRS observation, we tested the activities of the phospholipase enzymes known
      to act on phosphatidylcholine (PtdCho), a key component of phospholipid membranes
      and a source of choline for the neurotransmitter, acetylcholine (ACh). The
      activities of both phosphatidylcholine-specific phospholipase C (PC-PLC) and
      phospholipase D were severely diminished following Dox administration. The
      activity of PC-PLC was preserved when MESNA was co-administered with Dox;
      however, PLD activity was not protected. This study is the first to demonstrate
      the protective effects of MESNA on Dox-related protein oxidation, cognitive
      decline, phosphocholine (PCho) levels, and PC-PLC activity in brain and suggests
      novel potential therapeutic targets and strategies to mitigate CICI.

PMID- 30100996
TI  - Differential genomics and transcriptomics between tyrosine kinase inhibitor
      sensitive and -resistant BCR-ABL-dependent chronic myeloid leukemia.
AB  - Previously, it has been stated that the BCR-ABL fusion-protein is sufficient to
      induce Chronic Myeloid Leukemia (CML), but additional genomic-changes are
      required for disease progression. Hence, we profiled control and tyrosine kinase
      inhibitors (TKI) alone or in combination with other drug-treated CML-samples in
      different phases, categorized as drug-sensitive and drug-resistant on the basis
      of BCR-ABL transcripts, the marker of major molecular-response. Molecular
      profiling was done using the molecular-inversion probe-based-array, Human
      Transcriptomics-Array2.0, and Axiom-Biobank genotyping-arrays. At the transcript
      level, clusters of control, TKI-resistant and TKI-sensitive cases were correlated
      with BCR-ABL transcript-levels. Both at the gene- and exon-levels, up-regulation
      of MPO, TPX2, and TYMS and down-regulation of STAT6, FOS, TGFBR2, and ITK lead up
      regulation of the cell-cycle, DNA-replication, DNA-repair pathways and down
      regulation of the immune-system, chemokine- and interleukin-signaling, TCR, TGF
      beta and MAPK signaling pathways. A comparison between TKI-sensitive and TKI
      resistant cases revealed up-regulation of LAPTM4B, HLTF, PIEZO2, CFH, CD109,
      ANGPT1 in CML-resistant cases, leading to up-regulation of autophagy-, protein
      ubiquitination-, stem-cell-, complement-, TGFbeta- and homeostasis-pathways with
      specific involvement of the Tie2 and Basigin signaling-pathway. Dysregulated
      pathways were accompanied with low CNVs in CP-new and CP-UT-TKI-sensitive-cases
      with undetectable BCR-ABL-copies. High CNVs (previously reported gain of 9q34)
      were observed in BCR-ABL-independent and -dependent TKI, non-sensitive-CP-UT/AP
      UT/B-UT and B-new samples. Further, genotyping CML-CP-UT cases with BCR-ABL 0-to
      77.02%-copies, the identified, rsID239798 and rsID9475077, were associated with
      FAM83B, a candidate for therapeutic resistance. The presence of BCR-ABL,
      additional genetic-events, dysregulated-signaling-pathways and rsIDs associated
      with FAM83B in TKI-resistant-cases can be used to develop a signature-profile
      that may help in monitoring therapy.

PMID- 30100995
TI  - RNA sequencing reveals upregulation of a transcriptomic program associated with
      stemness in metastatic prostate cancer cells selected for taxane resistance.
AB  - Patients with metastatic castration-resistant prostate cancer (mCRPC) develop
      resistance to conventional therapies including docetaxel (DTX). Identifying
      molecular pathways underlying DTX resistance is critical for developing novel
      combinatorial therapies to prevent or reverse this resistance. To identify
      transcriptomic signatures associated with acquisition of chemoresistance we
      profiled gene expression in DTX-sensitive and -resistant mCRPC cells using RNA
      sequencing (RNA-seq). PC3 and DU145 cells were selected for DTX resistance and
      this phenotype was validated by immunoblotting using DTX resistance markers (e.g.
      clusterin, ABCB1/P-gp, and LEDGF/p75). Overlapping genes differentially regulated
      in the DTX-sensitive and -resistant cells were ranked by Gene Set Enrichment
      Analysis (GSEA) and validated to correlate transcript with protein expression.
      GSEA revealed that genes associated with cancer stem cells (CSC) (e.g., NES,
      TSPAN8, DPPP, DNAJC12, and MYC) were highly ranked and comprised 70% of the top
      25 genes differentially upregulated in the DTX-resistant cells. Established
      markers of epithelial-to-mesenchymal transition (EMT) and CSCs were used to
      evaluate the stemness of adherent DTX-resistant cells (2D cultures) and
      tumorspheres (3D cultures). Increased formation and frequency of cells expressing
      CSC markers were detected in DTX-resistant cells. DU145-DR cells showed a 2-fold
      increase in tumorsphere formation and increased DTX resistance compared to DU145
      DR 2D cultures. These results demonstrate the induction of a transcriptomic
      program associated with stemness in mCRPC cells selected for DTX resistance, and
      strengthen the emerging body of evidence implicating CSCs in this process. In
      addition, they provide additional candidate genes and molecular pathways for
      potential therapeutic targeting to overcome DTX resistance.

PMID- 30100997
TI  - Viral DNA integration and methylation of human papillomavirus type 16 in high
      grade oral epithelial dysplasia and head and neck squamous cell carcinoma.
AB  - This study evaluated the integration and methlyation of human papillomavirus type
      16 (HPV16) in head and neck squamous cell carcinoma (HNSCC) and its oral
      precursor, high-grade oral epithelial dysplasia (hgOED). Archival samples of
      HPV16-positive hgOED (N = 19) and HNSCC (N = 15) were evaluated, along with three
      HNSCC (UMSCC-1, -47 and -104) and two cervical cancer (SiHa and CaSki) cell
      lines. HgOED cases were stratified into three groups with increasing degrees of
      cytologic changes (mitosis, karyorrhexis and apoptosis). The viral load was
      higher and the E2/E6 ratio lower (indicating a greater tendency toward viral
      integration) in group 3 than in groups 1 or 2 (p = 0.002, 0.03). Methylation was
      not observed in hgOED cases and occurred variably in only three HNSCC cases
      (26.67%, 60.0% and 93.3%). In HNSCC cell lines, lower E7 expression correlated
      with higher levels of methylation. HgOED with increased cytologic change, now
      termed HPV-associated oral epithelial dysplasia (HPV-OED), exhibited an increased
      viral load and a tendency toward DNA integration, suggesting a potentially
      increased risk for malignant transformation. More detailed characterization and
      clinical follow-up of HPV-OED patients is needed to determine whether HPV-OED is
      a true precursor to HPV-associated HNSCC and to clarify the involvement of HPV in
      HNSCC carcinogenesis.

PMID- 30100998
TI  - cAMP-mediated autophagy inhibits DNA damage-induced death of leukemia cells
      independent of p53.
AB  - Autophagy is important in regulating the balance between cell death and survival,
      with the tumor suppressor p53 as one of the key components in this interplay. We
      have previously utilized an in vitro model of the most common form of childhood
      cancer, B cell precursor acute lymphoblastic leukemia (BCP-ALL), to show that
      activation of the cAMP signaling pathway inhibits p53-mediated apoptosis in
      response to DNA damage in both cell lines and primary leukemic cells. The present
      study reveals that cAMP-mediated survival of BCP-ALL cells exposed to DNA
      damaging agents, involves a critical and p53-independent enhancement of
      autophagy. Although autophagy generally is regarded as a survival mechanism, DNA
      damage-induced apoptosis has been linked both to enhanced and reduced levels of
      autophagy. Here we show that exposure of BCP-ALL cells to irradiation or
      cytotoxic drugs triggers autophagy and cell death in a p53-dependent manner.
      Stimulation of the cAMP signaling pathway further augments autophagy and inhibits
      the DNA damage-induced cell death concomitant with reduced nuclear levels of p53.
      Knocking-down the levels of p53 reduced the irradiation-induced autophagy and
      cell death, but had no effect on the cAMP-mediated autophagy. Moreover,
      prevention of autophagy by bafilomycin A1 or by the ULK-inhibitor MRT68921,
      diminished the protecting effect of cAMP signaling on DNA damage-induced cell
      death. Having previously proposed a role of the cAMP signaling pathway in
      development and treatment of BCP-ALLs, we here suggest that inhibitors of
      autophagy may improve current DNA damage-based therapy of BCP-ALL - independent
      of p53.

PMID- 30100999
TI  - Chk1 inhibition as a novel therapeutic strategy in melanoma.
AB  - Melanoma patients respond poorly to chemotherapies because they acquire drug
      resistance. Therapies that can overcome the resistance to inhibitors of the
      mutated BRAF protein kinase in melanoma are urgently needed. Chk1 protein kinase
      is a central component of the DNA damage response and plays a crucial role in
      controlling cell cycle progression. Analyses indicate that low mRNA expression of
      Chk1 is significantly associated with good overall survival of melanoma patients.
      To evaluate the effectiveness of Chk1 inhibitors in melanoma therapy, we have
      generated BRAF inhibitor (PLX4032 or vemurafenib) resistant melanoma cell lines
      (A375-PLX-R and WM9-PLX-R) from A375 and WM9, respectively. We observe that AKT
      (protein kinase B) is constitutively activated in A375-PLX-R, but not in WM9-PLX
      R cells, suggesting that these cells develop resistance to PLX4032 through
      different mechanisms. We show that a potent and specific inhibitor of Chk1
      (PF477736) is effective in reducing cell viability and colony formation of
      PLX4032-resistant cells. Even more impressively, PF477736 triggers PLX4032
      resistant melanoma cells to regain sensitivity to the PLX4032. Mouse xenograft
      studies show that treating A375-PLX-R derived tumors with combined PLX4032 and
      PF477736 significantly reduce tumor growth. Combined treatments with PLX4032 and
      PF477736 reduce the levels of total Chk1 protein and alter Chk1 phosphorylation
      at several sites in both PLX4032 sensitive and resistant melanoma cells.
      Combinatorial treatments with PLX4032 and PF477736 to melanoma cells
      substantially induce DNA damage and cell death. Our results suggest that Chk1
      inhibitors may provide new therapy options for melanoma patients.

PMID- 30101001
TI  - Correction: Ruxolitinib sensitizes ovarian cancer to reduced dose Taxol, limits
      tumor growth and improves survival in immune competent mice.
AB  - [This corrects the article DOI: 10.18632/oncotarget.21541.].

PMID- 30101002
TI  - Correction: Integrated epigenetic and genetic analysis identifies markers of
      prognostic significance in pediatric acute myeloid leukemia.
AB  - [This corrects the article DOI: 10.18632/oncotarget.25475.].

PMID- 30101000
TI  - PD-L1 expression comparison between primary and relapsed non-small cell lung
      carcinoma using whole sections and clone SP263.
AB  - We assessed the concordance, in terms of PD-L1 expression, between primary and
      metastatic non-small cell lung carcinoma (NSCLC) of different histotypes using
      validated SP263 clone. A few samples of local recurrences have also been
      analyzed. Whole sections of consecutive cases of primary NSCLC and paired
      relapses undergone surgical resection have been stained with PD-L1 clone SP263;
      for scoring purposes, a three-tiered system was applied using the following
      thresholds: <1%, 1-49% and >=50%. Eighty-four cases of paired primary and
      relapsed tumors from 83 patients were analyzed, including 75 metastases and 9
      local recurrences. Regarding metastases, when considering a cutoff of 1%,
      discrepancy in PD-L1 expression occurred in 9/75 (12%) paired samples (kappa
      value = 0.75); at 50% cutoff, discrepancy in PD-L1 expression was detected in
      7/75 (9.3%) of paired samples (kappa value = 0.61). Regarding recurrences, at 1%
      cutoff, the discrepancy in PD-L1 expression was seen in 3/9 (33%) paired samples
      and in all cases there was a gained PD-L1 expression; at 50% cutoff, 1/9 (11%)
      paired samples showed gained PD-L1 expression. Our data provide important
      information regarding the concordance between primary and relapsed NSCLC and the
      degree of reliability of metastatic sites in terms of PD-L1 expression
      evaluation.

PMID- 30101004
TI  - Authenticating Health Activity Data Using Distributed Ledger Technologies.
AB  - The on-demand digital healthcare ecosystem is on the near horizon. It has the
      potential to extract a wealth of information from "big data" collected at the
      population level, to enhance preventive and precision medicine at the patient
      level. This may improve efficiency and quality while decreasing cost of
      healthcare delivered by professionals. However, there are still security and
      privacy issues that need to be addressed before algorithms, data, and models can
      be mobilized safely at scale. In this paper we discuss how distributed ledger
      technologies can play a key role in advancing electronic health, by ensuring
      authenticity and integrity of data generated by wearable and embedded devices. We
      demonstrate how the Masked Authenticated Messaging extension module of the IOTA
      protocol can be used to securely share, store, and retrieve encrypted activity
      data using a tamper-proof distributed ledger.

PMID- 30101003
TI  - The radiation therapy options of intracranial hemangiopericytoma: An overview and
      update on a rare vascular mesenchymal tumor.
AB  - Hemangiopericytoma (HPC) is an extremely rare hypervascular tumor of mesenchymal
      lineage. It tends to recur and to develop distant metastases even many years
      after primary surgical resection. The management of recurrent and metastatic
      disease is not always so well defined. A complete surgical resection does not
      eliminate the high risk of local recurrences that occur in the central nervous
      system, often in the same surgical bed. However, treatment with adjuvant
      radiotherapy even in cases of complete resection remains controversial. Because
      of its rarity, there is no standard for treatment. We focused on radiotherapy
      treatment options, analyzing the literature and making a base on conduct further
      studies to establish the standard radiation dose to be used for locoregional
      control of such a complex and extremely rare disease and to help specialists to
      take the most appropriate therapeutic option.

PMID- 30101006
TI  - An end to end workflow for differential gene expression using Affymetrix
      microarrays.
AB  - In this article, we walk through an end-to-end Affymetrix microarray differential
      expression workflow using Bioconductor packages. This workflow is directly
      applicable to current "Gene" type arrays, e.g. the HuGene or MoGene arrays but
      can easily adapted to similar platforms. The data re-analyzed is a typical
      clinical microarray data set that compares inflammed and non-inflammed colon
      tissue in two disease subtypes. We will start from the raw data CEL files, show
      how to import them into a Bioconductor ExpressionSet, perform quality control and
      normalization and finally differential gene expression (DE) analysis, followed by
      some enrichment analysis. As experimental designs can be complex, a self
      contained introduction to linear models is also part of the workflow.

PMID- 30101005
TI  - Aneurysm wall enhancement in black blood MRI correlates with aneurysm size. Black
      blood MRI could serve as an objective criterion of aneurysm stability in near
      future.
AB  - The increasing number of incidental intracranial aneurysms creates a dilemma of
      which aneurysms to treat and which to observe. Clinical scoring systems consider
      risk factors for aneurysm rupture however objective parameters for assessment of
      aneurysms stability are needed. We retrospectively analysed contrast enhancing
      behaviour of un-ruptured aneurysms in the black blood magnetic resonance imaging
      (MRI) in N=71 patients with 90 aneurysms and assessed correlation between
      aneurysm wall contrast enhancement (AWCE) and aneurysm anatomy and clinical
      scoring systems. AWCE is associated with aneurysm height and height to width
      ratio in ICA aneurysms. AWCE is correlated to larger aneurysms in every
      anatomical location evaluated. However the mean size of the contrast enhancing
      aneurysms is significantly different between anatomical localizations indicating
      separate analyses for every artery. Clinical scoring systems like PHASES and
      UIATS correlate positively with AWCE in black blood MRI. MRI aneurysm wall
      contrast enhancement is a positive predictor for aneurysm instability and should
      be routinely assessed in follow up of incidental aneurysms. Aneurysms smaller
      than 7 mm with AWCE should be followed closely with focus on growth, as they may
      be prone to growth and rupture.

PMID- 30101007
TI  - Nonoperative management of complicated hiatal hernia after transhiatal
      esophagectomy- case report.
AB  - Introduction: Hiatal hernia is rare after transhiatal esophagectomy occurring in
      less than 2% of patients [5]. Due to the rare incidence of hiatal hernias after
      transhiatal esophagectomy overlooking this differential in a symptomatic patient
      can be problematic. Patients can presents with recurrent pneumonia, complaints of
      reflux, and in the case presented small bowel obstructions. Surgery has been the
      mainstay of treatment for symptomatic hiatal hernias. This case report poses that
      nonoperative management is a viable treatment option for patients with
      complicated hiatal hernias after transhiatal esophagectomy. Presentation of case:
      We present the case of a mechanical small bowel obstruction occurring at the
      esophageal hiatus in a patient four years after transhiatal esophagectomy. The
      patient was successfully managed nonoperatively with resolution of small bowel
      obstruction and persistent hiatal hernia. Conclusion: Hiatal hernias after
      transhiatal esophagectomy are a rare entity. Complications of these hernias with
      mechanical small bowel obstructions are even less described in the current
      literature. It is important to recognize hiatal hernias as a potential cause of
      obstructive symptoms after esophagectomy. While surgical intervention may be
      inevitable in certain population of patients. Initial nonoperative management is
      a viable treatment option and should be utilized in high risk operative patients.

PMID- 30101009
TI  - Impact of multidisciplinary tumor boards on patients with rectal cancer.
AB  - Omicronncological outcomes in patients with primary rectal cancer have markedly
      improved over the last few years, mainly due to the widespread application of the
      total mesorectal excision technique. This improvement should also be largely
      attributed to multiple specialties, other than colorectal surgery, such as
      radiology, oncology and pathology. Therefore, a multimodal approach is key to
      efficient and appropriate rectal cancer management. Multidisciplinary tumor (MDT)
      boards have become an important asset for the management and treatment of
      patients with rectal cancer, and a number of studies published to date suggest
      the beneficial effect of the multidisciplinary approach on the management of such
      patients. The available evidence demonstrates a modification of the treatment
      plan, attributed to the MDT implementation, in a non-negligible proportion of
      these patients. However, more studies are required in order to assess the exact
      impact of MDT boards on disease-free and overall survival of patients with
      primary rectal cancer.

PMID- 30101010
TI  - Prognostic significance of pre-treatment neutrophil-to-lymphocyte and platelet-to
      lymphocyte ratios in non-surgically treated uterine cervical carcinoma.
AB  - The aim of the present study was to assess the prognostic significance of the pre
      treatment neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio
      (PLR) and other clinicopathological characteristics in patients with non
      surgically treated uterine cervical carcinoma. The correlations of
      clinicopathological characteristics with overall and progression-free survival
      were determined in 98 Japanese patients who received non-surgical treatment for
      uterine cervical carcinoma between January 1997 and July 2013. Survival rates
      were calculated using the Kaplan-Meier method and potential prognostic indicators
      were assessed using a Cox proportional hazards model. A total of 68 patients
      (69.4%) had a high pre-treatment NLR (>=3.5) and 34 patients (34.7%) had a high
      pre-treatment PLR (>=212). Both NLR and PLR were found to be positively
      correlated with pre-treatment platelet counts. Multivariate analysis identified
      NLR and carcinoembryonic antigen level, but not PLR, as independent predictors of
      overall and progression-free survival. In conclusion, the present study
      identified two prognostic indicators for uterine cervical carcinoma, both of
      which can be easily and cost-effectively monitored via blood testing.

PMID- 30101011
TI  - Diagnosis of lung adenocarcinoma with left adrenal metastasis via transesophageal
      endoscopic ultrasound-guided fine-needle aspiration biopsy: A case report.
AB  - Lung cancer is generally diagnosed through traditional bronchoscopy by
      pulmonologists, whereas data on the application of transesophageal endoscopic
      ultrasound-guided fine-needle aspiration (EUS-FNA) for lung cancer diagnosis in
      China are very rarely reported. We herein describe a case of a 62-year-old woman
      who presented with non-productive cough and was found to have a pulmonary mass in
      the upper lobe of the right lung. The results of positron emission tomography
      revealed an elevated level of 18F-fluorodeoxyglucose accumulation (maximum
      standardized uptake value of 13.6) in the left adrenal gland. Thus, EUS-FNA was
      performed to identify the suspected metastasis to the left adrenal gland, and the
      histopathological examination of the bioptic specimen demonstrated an
      adenocarcinoma, confirming the value of EUS-FNA as a first-line minimally
      invasive approach for diagnosis and staging in patients with lung cancer.

PMID- 30101008
TI  - Cell cycle checkpoint control: The cyclin G1/Mdm2/p53 axis emerges as a strategic
      target for broad-spectrum cancer gene therapy - A review of molecular mechanisms
      for oncologists.
AB  - Basic research in genetics, biochemistry and cell biology has identified the
      executive enzymes and protein kinase activities that regulate the cell division
      cycle of all eukaryotic organisms, thereby elucidating the importance of site
      specific protein phosphorylation events that govern cell cycle progression.
      Research in cancer genomics and virology has provided meaningful links to
      mammalian checkpoint control elements with the characterization of growth
      promoting proto-oncogenes encoding c-Myc, Mdm2, cyclins A, D1 and G1, and
      opposing tumor suppressor proteins, such as p53, pRb, p16INK4A and p21WAF1, which
      are commonly dysregulated in cancer. While progress has been made in identifying
      numerous enzymes and molecular interactions associated with cell cycle checkpoint
      control, the marked complexity, particularly the functional redundancy, of these
      cell cycle control enzymes in mammalian systems, presents a major challenge in
      discerning an optimal locus for therapeutic intervention in the clinical
      management of cancer. Recent advances in genetic engineering, functional genomics
      and clinical oncology converged in identifying cyclin G1 (CCNG1 gene) as a
      pivotal component of a commanding cyclin G1/Mdm2/p53 axis and a strategic locus
      for re-establishing cell cycle control by means of therapeutic gene transfer. The
      purpose of the present study is to provide a focused review of cycle checkpoint
      control as a practicum for clinical oncologists with an interest in applied
      molecular medicine. The aim is to present a unifying model that: i) clarifies the
      function of cyclin G1 in establishing proliferative competence, overriding p53
      checkpoints and advancing cell cycle progression; ii) is supported by studies of
      inhibitory microRNAs linking CCNG1 expression to the mechanisms of carcinogenesis
      and viral subversion; and iii) provides a mechanistic basis for understanding the
      broad-spectrum anticancer activity and single-agent efficacy observed with
      dominant-negative cyclin G1, whose cytocidal mechanism of action triggers
      programmed cell death. Clinically, the utility of companion diagnostics for
      cyclin G1 pathways is anticipated in the staging, prognosis and treatment of
      cancers, including the potential for rational combinatorial therapies.

PMID- 30101012
TI  - Extraskeletal osteosarcoma in right neck subcutaneous tissue: A case report of an
      extremely rare tumour.
AB  - Extraskeletal osteosarcoma (ESOS) is a rare soft-tissue sarcoma that is treated
      with surgical resection, chemotherapy and radiotherapy; however, as it is now
      considered to be radiation resistance, it is associated with conflicting
      management principles and poor outcomes. A multimodality approach is currently
      used to treat ESOS, which entails the incorporation of multidrug chemotherapy
      and/or radiotherapy coupled with surgery to obtain the best outcome; however,
      there are many factors that influence the treatment effects and clinical outcomes
      of ESOS. In the present study, a case of an 81-year-old man who suffered from
      primary ESOS in the subcutaneous tissue of the right-hand side of the neck was
      reported. The patient was treated several times with partial resection and once
      with radiotherapy, and was still living following 3 years of follow-up. Thus, the
      present case report demonstrated that surgical resection and postoperative
      radiotherapy regimens may be favourable in the short term with a disease-free
      survival of ~15 months; however, patients are prone to relapse.

PMID- 30101013
TI  - Induction chemotherapy in patients with resectable laryngeal cancer: A meta
      analysis.
AB  - Head and neck squamous cell carcinoma (SCC) ranks 6th among the most frequently
      diagnosed carcinomas globally. Laryngeal carcinoma is quite common, and 95% of
      the cases are SCCs. Since the introduction of larynx-preserving surgery,
      induction chemotherapy (IC) has played a substantial role. The aim of IC is to
      shrink or downstage primary laryngeal carcinomas, increasing the chances of
      complete surgical removal, particularly in cases with advanced but potentially
      resectable lesions. The aim of the present study was to investigate the value of
      IC in patients with resectable laryngeal cancer. A meta-analysis was performed of
      randomized controlled trials (1985-2017) investigating the effect of IC on
      survival, disease control, larynx-preserving surgery and disease-free survival.
      Engauge-Digitizer software was used to construct Kaplan-Meier curves and RevMan
      software was used for the analysis of the data. A total of 12 trials (4,320
      patients) were included. There was no significant difference in local recurrence
      or locoregional control between patients receiving and those not receiving IC
      (P>0.05). However, the experimental group (IC) exhibited a lower propensity for
      distant metastasis by 11.7% (95% confidence interval: 10.3-13.3%, P=0.02)
      compared with the control group (no IC). Among patients with laryngeal cancer,
      larynx preservation was possible in those who responded well to IC, without a
      significant decrease in survival compared with radical surgery (P<0.05). Taking
      into consideration these findings, IC confers an advantage in terms of lowering
      the risk of distant metastasis in patients with resectable laryngeal carcinoma,
      and enables laryngeal preservation in responders. Moreover, IC increases the
      overall survival rate in patients with locally advanced but resectable LC.

PMID- 30101014
TI  - Paraneoplastic cerebellar degeneration associated with breast cancer: A case
      report and review of the literature.
AB  - Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication
      of cancer characterized by rapid development of cerebellar ataxia. We herein
      present a case of a 67-year-old female patient with PCD caused by breast cancer.
      The patient presented with progressively worsening cerebellar deficits that had
      been misdiagnosed for several months prior to the identification of the anti-Yo
      autoantibodies in the serum. A whole-body positron emission tomography/computed
      tomography scan revealed a lesion in the lower outer quadrant of the left breast
      with slightly increased metabolism. On mammography, a lobulated high-density mass
      was identified in the left breast. The patient underwent left breast lumpectomy
      and the histological examination confirmed the presence of an invasive ductal
      carcinoma. After breast surgery, the patient exhibited marked neurological
      improvement at the 12-month follow-up. Therefore, it is crucial that clinicians
      include paraneoplastic neurological syndromes in the differential diagnosis of
      neurological disorders. The detection of characterized onconeural antibodies in
      the serum or cerebrospinal fluid may provide guidance in the search for an
      underlying tumor.

PMID- 30101015
TI  - Atypical presentation of a cushion sign-positive stomach gastrointestinal stromal
      tumor with cystic formation: A case report.
AB  - Gastrointestinal stromal tumors (GIST) typically appear as solid masses, and
      cystic formation is uncommon. Most stomach GISTs with cystic formation progress
      outside the gastric wall and are frequently misdiagnosed as epigastric cystic
      tumors derived from pancreas or liver. An asymptomatic 72-year-old male underwent
      esophagogastroduodenoscopy, which revealed a submucosal tumor (SMT),
      approximately 50 mm in diameter, at the anterior wall of the gastric angle. The
      SMT was very soft with positive cushion sign. Endoscopic ultrasonography and
      contrast-enhanced computed tomography revealed that the SMT was a cystic tumor
      with solid component. Laparoscopic and endoscopic cooperative surgery were
      performed to remove the tumor. Histopathological analysis revealed that the tumor
      was a GIST with cystic formation. To the best of our knowledge, this the first
      documented case of a cushion sign-positive stomach GIST with cystic formation,
      which had mainly developed inside the stomach. This case suggests that we should
      keep in mind the possibility of cystic formation of GIST when the tumor has a
      solid component, even if it appears as a cushion sign-positive SMT.

PMID- 30101016
TI  - Safe administration of bevacizumab combination chemotherapy for the patients with
      recurrent cervical cancer after pelvic radiotherapy: Two case reports.
AB  - In Japan, bevacizumab has not been proven either effective or safe for the
      treatment of recurrent cervical cancer. The present study reported two cases in
      which bevacizumab combination chemotherapy was safely administered for recurrent
      cervical cancer following pelvic radiotherapy. Case 1 was a 62-year-old woman
      with stage IIIB squamous cell carcinoma of the cervix who had received whole
      pelvic external beam radiotherapy (WPEBRT) at a dose of 50.4 Gy and high dose
      rate intra-cavitary brachytherapy at a dose of 24 Gy to the pelvis one year
      earlier. For recurrent cervical cancer, chemotherapy with paclitaxel, carboplatin
      and bevacizumab was administered for six cycles. Case 2 was a 52-year-old woman
      with stage IIB squamous cell carcinoma of the cervix who had received WPEBRT at a
      dose of 50.4 Gy to the pelvis 11 years earlier. For lymph node and liver
      metastases, chemotherapy with paclitaxel, cisplatin, and bevacizumab was
      administered for six cycles. Although grade 2 proteinuria was observed in one of
      these patients, there were no intestinal perforation, fistula, hypertension,
      proteinuria or thrombosis events, which are the characteristic adverse reactions
      associated with bevacizumab. Hematotoxicity was also manageable. Regarding the
      antitumor effect, case 1 demonstrated a complete response, whereas case 2
      resulted in stable disease.

PMID- 30101017
TI  - Ultrasound-guided intranodal lymphangiography with lipiodol for treatment of
      chylous ascites following surgery for ovarian cancer: A case report.
AB  - Although lymphadenectomy for gynecological cancer is often associated with
      chylous leakage, the proper management of this complication remains a matter of
      debate. In the present study a case of chylous leakage successfully treated with
      lipiodol lymphangiography is described. A 33-year-old patient with ovarian cancer
      experienced chylous leakage following total abdominal hysterectomy, bilateral
      salpingo-oophorectomy, omentectomy, and pelvic and para-aortic lymphadenectomy.
      The volume of fluid in the abdominal drainage tube increased to 800-1,000 ml/day
      on postoperative day (POD)3. The patient was started on a fat-restricted diet on
      POD3 and octreotide on POD21, but the volume of the discharge remained unchanged.
      Lipiodol lymphangiography was performed on POD62, which reduced the leakage, and
      the patient was discharged on POD95. Therefore, lipiodol lymphangiography
      effectively resolved chylous leakage following surgery for gynecological cancer.
      The aim of the present study was to report the clinical effectiveness of lipiodol
      lymphangiography in resolving chylous leakage in such cases, and to summarize the
      methods used and complications encountered.

PMID- 30101018
TI  - Double cancer comprising malignant pleural mesothelioma and squamous cell
      carcinoma of the lung treated with radiotherapy: A case report.
AB  - Pleurectomy/decortication (P/D) is the surgical treatment of choice for early
      malignant mesothelioma, but it remains unclear whether radiotherapy along with
      P/D should be used as multimodal treatment for this disease. We herein present
      the case of a 76-year-old man with a history of asbestos exposure who was
      diagnosed with left-sided malignant pleural mesothelioma in February 2010. The
      patient underwent chemotherapy with a combination of cisplatin and pemetrexed and
      achieved stable disease, after which time he was kept under observation. A
      positron emission tomography/computed tomography scan performed in February 2011
      revealed nodular shadows with fluorodeoxyglucose uptake in S3 of the left lung;
      using bronchoscopy, the patient was diagnosed with stage IIB (cT3N0M0) primary
      squamous cell carcinoma. Chemoradiotherapy with vinorelbine and 60 Gy/20 fr
      radiotherapy was performed, and a partial response was obtained, suggesting that
      the radiotherapy used to treat the carcinoma of the lung may have also helped
      control the disease activity of the pre-existing mesothelioma. The present case
      indicates the value of radiotherapy in the treatment of malignant mesothelioma.
      The aim of the present study was to examine the possibility of new multimodal
      treatments for mesothelioma, along with a discussion of the relevant literature.

PMID- 30101019
TI  - Lymphoproliferative disorder with pathological fracture of the femur in a patient
      with rheumatoid arthritis treated with methotrexate: A case report.
AB  - Methotrexate (MTX) is the key drug for the treatment of rheumatoid arthritis
      (RA). MTX-treated RA has been associated with the development of
      lymphoproliferative disorders (LPDs). Notably, the hyperimmune state of RA itself
      or the immunosuppressive state induced by MTX administration may contribute to
      development of LPD. Furthermore, Epstein-Barr virus (EBV) has been indicated to
      contribute to the development of MTX-LPD. MTX-associated LPD (MTX-LPD) may affect
      nodal or extranodal sites, including the gastrointestinal tract, skin, lungs,
      kidneys, and soft tissues, at an almost equal frequency. However, it is rare for
      MTX-LPD to manifest as multiple bone tumors with a pathological fracture. The
      present study reported the case of a 46-year-old Japanese woman with RA who had
      complications of EBV-positive MTX-LPD during an approximate 5-year course of MTX
      therapy. The present study indicated a rare case in which the LPD had spread to
      multiple bones in a patient with a pathologic fracture. Notably, the LPD was
      subclassified as diffuse large B-cell lymphoma (DLBCL).

PMID- 30101020
TI  - Favorable response to pemetrexed, cisplatin and bevacizumab in invasive mucinous
      adenocarcinoma: A case report and literature review.
AB  - Invasive mucinous adenocarcinoma (IMA) was formerly referred to as mucinous
      bronchioloalveolar carcinoma. The lack of effective chemotherapy and
      comprehensive treatment for this type of tumor poses a great challenge in
      clinical practice. We herein report the case of a male patient with IMA who was
      treated with a combination of pemetrexed (500 mg/m2), cisplatin (75 mg/m2) and
      bevacizumab (15 mg/kg) as first-line chemotherapy. The patient achieved
      significant radiological improvement with 6 courses of this regimen. After the
      tumor progressed, the patient again achieved marked improvement with an
      additional 4 courses of the same regimen. The patient survived for a total of 30
      months after the first chemotherapy. Therefore, bevacizumab in combination with
      pemetrexed/cisplatin may be an effective strategy for the treatment of IMA. The
      available literature on this chemotherapy regimen was also reviewed and discussed
      in the present study.

PMID- 30101021
TI  - Pure small-cell carcinoma of the prostate presenting with increasing prostate
      specific antigen levels: A case report and review of the literature.
AB  - The incidence of prostatic cancer (PCa) has increased significantly, and the
      measurement of prostate-specific antigen (PSA) is an effective screening tool for
      its diagnosis. PCa includes a number of specific clinicopathological types,
      including squamous cell, urothelial, adenoid cystic and small-cell carcinoma,
      among which small-cell carcinoma of the prostate (SCCP) is extremely rare,
      accounting for <0.5% of all PCa cases. SCCP is very aggressive and the majority
      of the cases have a poor prognosis, with a mean survival of ~5 months; it also
      exhibits specific clinicopathological characteristics and may be divided into two
      subtypes, namely pure and mixed SCCP. According to the previous literature on
      PubMed, pure SCCP is not associated with an increase in serum PSA levels.
      However, the rare case presented herein exhibited an increasingly abnormal serum
      PSA level. The patient was aged 66 years and had a PSA level of 56.78 ng/ml
      (normal, <4 ng/ml); he was diagnosed with pure SCCP, underwent radical
      prostatectomy and has remained disease-free during the follow-up. Similar cases
      previously published on PubMed were also reviewed, and considerations of survival
      status and treatment options were analyzed.

PMID- 30101022
TI  - Cost-effectiveness and safety of the molecular targeted drugs afatinib, gefitinib
      and erlotinib as first-line treatments for patients with advanced EGFR mutation
      positive non-small-cell lung cancer.
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs),
      including gefitinib, erlotinib and afatinib are standard first-line treatments
      for EGFR gene mutation-positive non-small cell lung cancer. The present study
      aimed to compare the cost-effectiveness of using erlotinib, afatinib or
      gefitinib. The safety of EGFR-TKIs was also investigated. Expected costs were
      calculated based on data from patients with advanced EGFR mutation-positive non
      small-cell lung cancer who were treated with gefitinib, erlotinib or afatinib.
      Literature was collected to obtain the necessary clinical information for
      calculating the probability and the validity of each chemotherapy. Median
      survival time (MST) was used to evaluate the therapeutic effect of the regimens.
      The cost-effectiveness ratio was calculated using expected costs and MSTs for the
      three regimens. The cost-effectiveness ratio per month was JPY 386,859.4/MST for
      afatinib, JPY 264,788.7/MST for gefitinib and JPY 397,039.9/MST for erlotinib.
      Significant differences were observed between the three groups (p<0.001). The
      incremental cost-effectiveness ratio (ICER) of gefitinib compared with afatinib
      per month was JPY 122,070.7/MST. The ICER of gefitinib compared with erlotinib
      was JPY -69,605.9/MST. Adverse effects of Grade 3 and higher, including diarrhoea
      (28.6%) and paronychia (14.3%) were observed in the afatinib treatment group.
      Paronychia (23.1%) was observed in the erlotinib treatment group, while none were
      observed in the gefitinib treatment group. These findings demonstrate that
      gefitinib is more cost effective in comparison with the afatinib and erlotinib
      regimens, although the afatinib and erlotinib regimens were well-tolerated and
      produce sufficient effects.

PMID- 30101024
TI  - Primary ovarian signet ring cell carcinoma: A rare case report.
AB  - Signet ring cell carcinoma (SRCC) of the ovary is most commonly metastatic from a
      primary lesion. Primary ovarian SRCC is rare, and the distinction between primary
      and metastatic SRCC of the ovary may be difficult. We herein present a case of
      primary SRCC of the ovary in a 54-year-old woman presenting with a right ovarian
      mass sized 20.5*16.5*11.5 cm. Total abdominal hysterectomy with bilateral
      salpingo-oophorectomy, partial omentectomy and incidental appendectomy were
      performed. Upon histological examination, mucinous carcinoma composed
      predominantly of signet ring cells was observed in the right ovary. The results
      of immunohistochemical examination included diffuse positivity for cytokeratin
      (CK)7 and CK20, but the tumor was negative for estrogen receptor, progesterone
      receptor, caudal type homeobox 2 and Wilms' tumor gene 1. A preoperative computed
      tomography (CT) scan of the abdomen and a postoperative positron emission
      tomography-CT scan did not reveal any suspicious extraovarian lesions. Based on
      the histological and clinicoradiological examinations, this case was diagnosed as
      a primary ovarian SRCC.

PMID- 30101023
TI  - Tuberculoma with phlegmon-like symptoms mimicking soft tissue sarcoma in the
      wrist: A case report.
AB  - Despite the increasing incidence of tuberculosis, even in developed countries
      like Japan, tuberculoma is a relatively uncommon disease. Furthermore, given the
      rarity of tuberculoma, a definitive diagnosis is often delayed. We herein present
      the case of a 79-year-old man who presented with an erythematous and warm mass in
      the left forearm. Radiography revealed calcification of the wrist's volar side,
      and magnetic resonance imaging revealed a mosaic pattern at the lesion. Soft
      tissue sarcoma of the wrist was suspected, and an incisional biopsy was
      performed, which revealed numerous yellow rice bodies. A rapid pathological
      evaluation revealed caseous necrosis and Langhans giant cells, and a histological
      evaluation confirmed the diagnosis of tuberculoma. All the rice bodies were
      resected and the patient received postoperative antibiotic treatment with
      pyrazinamide, isoniazid, rifampicin and ethambutol. However, the patient
      developed hepatic insufficiency during treatment, and the regimen was
      discontinued. The patient had not experienced recurrence 1 year after the
      treatment. In conclusion, tuberculoma should be considered in the differential
      diagnosis of a wrist mass mimicking an inflamed soft tissue tumor.

PMID- 30101025
TI  - Descending necrotizing mediastinitis after sequestrectomy in a patient with
      bisphosphonate-induced osteonecrosis of the jaw: A case report.
AB  - An 83-year-old woman underwent mastectomy for breast cancer of the right breast
      in 2008. In addition to hormone therapy and irradiation, zoledronate was started
      for bone metastasis 6 months postoperatively. Five years after the operation, the
      patient developed osteonecrosis of the jaw, and underwent sequestrectomy because
      of uncontrollable pain in the mandible. The patient visited our hospital for a 1
      week history of fever and right facial swelling with pain, and was diagnosed with
      right mandibular cellulitis. Despite antibiotic therapy, the patient fell into
      shock. Follow-up computed tomography showed gas formation extending down to the
      posterior mediastinum, which was compatible with descending necrotizing
      mediastinitis (DNM). The patient succumbed to septicemia on the third hospital
      day. The mortality rate of DNM greatly increases in patients with advanced cancer
      because clinicians cannot perform radical treatment due to the impaired general
      condition and limited life expectancy. DNM advances by the hour; therefore,
      repeated computed tomography is essential when antibiotic therapy does not
      improve the patient's condition. Attention must be paid to detect signs of DNM in
      such patients. To the best of our knowledge, this is the first report in English
      regarding DNM caused by bisphosphonate-induced osteonecrosis of the jaw.

PMID- 30101026
TI  - Management of MANEC of the colon and rectum: A comprehensive review of the
      literature.
AB  - Mixed adeno-neuroendocrine carcinoma (MANEC) is a rare pathological diagnosis
      recently acknowledged by the World Health Organization in 2010. MANEC is a
      neoplasm characterized by significant histological heterogeneity and is
      characterized by the simultaneous presence of both adenocarcinomatous and
      neuroendocrine differentiation; their definition includes each component found in
      at least 30% of the tumor. Colorectal MANEC constitutes an uncommon type of
      malignant tumor. The true prevalence of colorectal MANEC has not been precisely
      defined and published studies are limited to case reports and small case series.
      The aim of the present review was to accumulate the existing evidence on
      colorectal MANEC with special attention to the clinicopathological
      characteristics, management and survival rates of patients diagnosed with this
      malignancy. A total of 20 studies (16 case reports and 4 retrospective cohorts)
      reported outcomes for patients with colorectal MANEC and were finally considered
      eligible for analysis. The results of the present study show that patients with
      early stage MANEC have more favorable survival compared to those diagnosed in
      advanced stages. Due to its neuroendocrine nature, which is characterized by
      rapid progression, MANEC is diagnosed in advanced stages in the majority of cases
      and thus potentially explains the poor survival rates. Because of its aggressive
      nature and high recurrence rate, adjuvant chemotherapy constitutes a critical
      part of the treatment and significantly improves survival. Further larger studies
      are needed in order to establish guidelines for the treatment of these rare
      lesions.

PMID- 30101027
TI  - Ruptured hepatoblastoma successfully treated with cisplatin monochemotherapy: A
      case report.
AB  - Traditionally, ruptured hepatoblastoma is considered a high-risk occurrence,
      necessitating a chemotherapy regimen usually consisting of cisplatin alternating
      with carboplatin plus doxorubicin, based on International Childhood Liver Tumours
      Strategy Group studies. However, ruptured hepatoblastomas with intact hepatic
      capsules may represent a unique subgroup that may be successfully treated with
      TAE, cisplatin monotherapy, and surgical excision. We herein present a case of
      ruptured hepatoblastoma (pretreatment tumor extension stage II) in a 1-year-old
      female patient that was successfully managed with transarterial embolization
      (TAE), eight courses of cisplatin chemotherapy and surgical removal. The patient
      currently remains disease-free for >12 months. Given the rarity of ruptured
      hepatoblastomas, further study of patients within this subgroup is required to
      confirm the findings of the present study.

PMID- 30101028
TI  - Malignant potential of epithelioid angiomyolipomas of the liver: A case report
      and comprehensive review of the literature.
AB  - Hepatic epithelioid angiomyolipoma (HEAML) is a rare mesenchymal tumor that has
      been reported to have malignant potential. We herein describe a rare case of
      atypical HEAML. A 43-year-old Caucasian male patient visited his general
      practitioner due to a productive cough persisting for >2 months. During
      evaluation with several imaging tests, a chest computed tomography (CT)
      incidentally revealed a well-demarcated lesion in the caudate lobe of the liver,
      sized 7 cm. An abdominal magnetic resonance imaging examination confirmed the
      findings of the CT. The possibility of hepatocellular carcinoma at that time
      could not be excluded. Due to inconclusive cross-sectional imaging, the patient
      underwent left hepatectomy with additional resection of segment I. The patient's
      postoperative course was uneventful. A diagnosis of 'atypical' HEAML was
      established in the present case. The majority of HEAMLs are considered to be
      benign, although there are several reported cases exhibiting malignant behavior,
      such as tumor growth, presence of atypical cells, recurrence after surgical
      resection, metastasis and invasive growth into the liver parenchyma and alongside
      the vessels. From 2000 onwards, 19 cases of malignant hepatic AML have been
      reported. Malignant transformation is considered to occur mostly in the
      epithelioid subtype. To that end, when epithelioid or atypical characteristics
      are identified on preoperative biopsy, resection is indicated due to the high
      probability of malignancy.

PMID- 30101030
TI  - Erratum: Adrenal collision tumor (parachordoma and ganglioneuroma): A case
      report.
AB  - [This corrects the article DOI: 10.3892/mco.2018.1610.].

PMID- 30101029
TI  - Coexistence of adenomyosis, adenocarcinoma, endometrial and myometrial lesions in
      resected uterine specimens.
AB  - The present study was conducted to identify endometrial and myometrial lesions
      coexisting with adenomyosis, and to evaluate the clinicopathological
      characteristics of endometrial adenocarcinomas associated with adenomyosis. A
      retrospective analysis of the resected uterine specimens of 319 patients with
      adenomyosis admitted between January 1, 2014 and August 1, 2017 was performed.
      The endometrial and myometrial lesions coexisting with adenomyosis were
      evaluated. The clinicopathological prognostic factors, including tumor grade,
      myometrial invasion, lymphovascular space involvement, lymph node invasion,
      pathological stage and recurrence, were analysed. For data analysis, the Chi
      squared test was used and a P-value of <0.05 was considered to indicate
      statistically significant differences. The mean age of the patients was 52.1
      years. A total of 32 patients had endometrial carcinoma associated with
      adenomyosis. In addition to endometrioid adenocarcinoma of different grades, rare
      clear cell carcinoma cases were also observed. Two cases of malignant mesenchymal
      tumors (one low-grade endometrial stromal sarcoma and one leiomyosarcoma) were
      also diagnosed. Therefore, patients presenting with abnormal uterine bleeding
      should undergo thorough evaluation for the presence of adenomyosis and/or
      leiomyoma(s). Although the cases of endometrial adenocarcinoma associated with
      adenomyosis generally had a good prognostic outcome, there were also rare cases
      of patients with agressive tumor morphology. The inflammatory and tissue response
      arising around the foci of adenomyosis generate a preventive mechanism against
      the invasion of adenocarcinomas coexisting with adenomyosis. This response is
      likely the primary mechanism underlying the good clinical course of these tumors.
      Therefore, the presence of adenomyosis may be an important factor for the
      determination of prognosis.

PMID- 30101031
TI  - Resorbable Nanocomposites with Bone-Like Strength and Enhanced Cellular Activity.
AB  - Bone cements for treatment of fractures at weight-bearing sites are subjected to
      dynamic physiological loading from daily activities. An ideal bone cement rapidly
      sets after injection, exhibits bone-like strength, stimulates osteogenic
      differentiation of endogenous cells, and resorbs at a rate aligned with patient
      biology. However, currently available materials fall short of these targeted
      properties. Nanocrystalline hydroxyapatite (nHA) enhances osteogenic
      differentiation, new bone formation, and osteoclast differentiation activity
      compared to amorphous or micron-scale crystalline hydroxyapatite. However, the
      brittle mechanical properties of nHA precludes its use in treatment of weight
      bearing bone defects. In this study, we report settable nHA-poly(ester urethane)
      (PEUR) nanocomposites synthesized from nHA, lysine triisocyanate (LTI), and
      poly(caprolactone) triol via a solvent-free process. The nanocomposites are
      easily mixed and injected using a double-barrel syringe, exhibit mechanical
      properties exceeding those of conventional bone cements, enhance mineralization
      of osteoprogenitor cells in vitro, and undergo osteoclast-mediated degradation in
      vitro. This combination of properties cannot be achieved using other
      technologies, which underscores the potential of nHA-PEUR nanocomposites as a new
      approach for promoting bone healing at weight-bearing sites.

PMID- 30101032
TI  - Occupational stress among medical residents in educational hospitals.
AB  - Background: Occupational stress and its related psychological strain is a concern
      among resident doctors that may affect patient care adversely. Residents face
      many stresses because of their high job demands in delivery of hospital care.
      They are often subject to work load and pressure due to direct involvement with
      patients, prolonged working hours, poor job opportunities and low support. Their
      multiple educational and clinical roles can also affect their performance and
      quality of personal or professional life. The aim of this study was to evaluate
      the occupational stress among residents of various medical specialties.We aimed
      to explore the reasons of occupational stress in residents' life and determine
      how we can enhance the stress-coping strategies and create more suitable
      conditions. Methods: This cross-sectional analytical-descriptive study was
      conducted on all medical residents with various specialties in Shiraz University
      of Medical Sciences. Data was collected using Osipow occupational stress
      questionnaire and analyzed by SPSS software version 17. Results: The response
      rate was 88.8%. The average stress score of all residents was 156.35 out of 250.
      The highest and lowest average stress scores belonged to gynecology and
      dermatology specialties, respectively. The highest average score of the stress
      factors was related to the workload with the score of 35.09 of 50 (moderate to
      severe stress). The total stress score had a significant relationship with age (P
      = 0.030) and sex (P = 0.009) as well as lack of time to get the needed healthy
      meals (P = 0.047), high work hours (P < 0.01), surgical specialties (P < 0.01)
      and on call shift (P < 0.01). Conclusion: Since most of the stressors were
      related to the workload, interventions such workload reduction, education about
      occupational stress and its management, promoting interpersonal relations and
      more supportive measures are recommended.

PMID- 30101033
TI  - Digital health in the Americas: advances and challenges in connected health.
AB  - In 2005, all WHO Member States pledged to fight for universal health coverage
      (UHC). The availability of financial, human and technological resources seems to
      be necessary to develop efficient health policies and also to offer UHC. One of
      the main challenges facing the health sector comes from the need to innovate
      efficiently. The intense use of information and communication technologies (ICTs)
      in the health field evidences a notable improvement in results obtained by
      institutions, health professionals and patients, principally in developed
      countries. In the Americas, the relationship between economic development and
      health innovation is not particularly evident. Data from 19 of 35 countries
      surveyed in the 2015 Third Global Survey on eHealth for the region of the
      Americas were analysed. 52.6% of the countries of the Americas have a national
      policy or strategy for UHC. 57.9% of the countries in the sample indicate that
      they have a national eHealth policy or strategy, but only 26.3% have an entity
      that supervises the quality, safety and reliability regulations for mobile health
      applications. The survey data indicate that high-income and low-income to middle
      income countries show higher percentages in relation to the existence of entities
      that promote innovation. These countries also exceed 60%-compared with 40% and
      50% in lower-income countries-in all cases regarding the use of eHealth
      practices, such as mobile health, remote patient monitoring or telehealth. 100%
      of low-income countries report offering ICT training to healthcare professionals,
      compared with 83% of wealthy countries and 81% of middle-income to high-income
      countries.

PMID- 30101035
TI  - Grasp Detection for Assistive Robotic Manipulation.
AB  - In this paper, we present a novel grasp detection algorithm targeted towards
      assistive robotic manipulation systems. We consider the problem of detecting
      robotic grasps using only the raw point cloud depth data of a scene containing
      unknown objects, and apply a geometric approach that categorizes objects into
      geometric shape primitives based on an analysis of local surface properties.
      Grasps are detected without a priori models, and the approach can generalize to
      any number of novel objects that fall within the shape primitive categories. Our
      approach generates multiple candidate object grasps, which moreover are
      semantically meaningful and similar to what a human would generate when
      teleoperating the robot-and thus should be suitable manipulation goals for
      assistive robotic systems. An evaluation of our algorithm on 30 household objects
      includes a pilot user study, confirms the robustness of the detected grasps and
      was conducted in real-world experiments using an assistive robotic arm.

PMID- 30101037
TI  - How Solvent Affects C-H Activation and Hydrogen Production Pathways in
      Homogeneous Ru-Catalyzed Methanol Dehydrogenation Reactions.
AB  - Insights into the mechanism of the catalytic cycle for methanol dehydrogenation
      catalyzed by a highly active PNP pincer ruthenium complex in methanol solvent are
      presented, using DFT-based molecular dynamics with an explicit description of the
      solvent, as well as static DFT calculations using microsolvation models. In
      contrast to previous results, we find the amido moiety of the catalyst to be
      permanently protonated under catalytic conditions. Solvent molecules actively
      participate in crucial reaction steps and significantly affect the reaction
      barriers when compared to pure gas-phase models, which is a direct result of the
      enhanced solvent stabilization of methoxide anion intermediates. Further, the
      calculations reveal that this system does not operate via the commonly assumed
      Noyori-type outer-sphere metal-ligand cooperative pathway. Our results show the
      importance of incorporating a molecular description of the solvent to gain a
      deeper and accurate understanding of the reaction pathways, and stress on the
      need to involve explicit solvent molecules to model complex catalytic processes
      in a realistic manner.

PMID- 30101034
TI  - Counterbalance: modulation of VEGF/VEGFR activities by TNFSF15.
AB  - Vascular hyperpermeability occurs in angiogenesis and several pathobiological
      conditions, producing elevated interstitial fluid pressure and lymphangiogenesis.
      How these closely related events are modulated is a fundamentally important
      question regarding the maintenance of vascular homeostasis and treatment of
      disease conditions such as cancer, stroke, and myocardial infarction. Signals
      mediated by vascular endothelial growth factor receptors, noticeably VEGFR-1, -2,
      and -3, are centrally involved in the promotion of both blood vessel and
      lymphatic vessel growth. These signaling pathways are counterbalanced or, in the
      case of VEGFR3, augmented by signals induced by tumor necrosis factor superfamily
      15 (TNFSF15). TNFSF15 can simultaneously downregulate membrane-bound VEGFR1 and
      upregulate soluble VEGFR1, thus changing VEGF/VEGFR1 signals from pro-angiogenic
      to anti-angiogenic. In addition, TNFSF15 inhibits VEGF-induced VEGFR2
      phosphorylation, thereby curbing VEGFR2-mediated enhancement of vascular
      permeability. Third, and perhaps more interestingly, TNFSF15 is capable of
      stimulating VEGFR3 gene expression in lymphatic endothelial cells, thus
      augmenting VEGF-C/D-VEGFR3-facilitated lymphangiogenesis. We discuss the
      intertwining relationship between the actions of TNFSF15 and VEGF in this review.

PMID- 30101038
TI  - A Survey on Automated Food Monitoring and Dietary Management Systems.
AB  - Healthy diet with balanced nutrition is key to the prevention of life-threatening
      diseases such as obesity, cardiovascular disease, and cancer. Recent advances in
      smartphone and wearable sensor technologies have led to a proliferation of food
      monitoring applications based on automated food image processing and eating
      episode detection, with the goal to conquer drawbacks of the traditional manual
      food journaling that is time consuming, inaccurate, underreporting, and low
      adherent. In order to provide users feedback with nutritional information
      accompanied by insightful dietary advice, various techniques in light of the key
      computational learning principles have been explored. This survey presents a
      variety of methodologies and resources on this topic, along with unsolved
      problems, and closes with a perspective and boarder implications of this field.

PMID- 30101036
TI  - Conformational Sampling of the Intrinsically Disordered C-Terminal Tail of DERA
      Is Important for Enzyme Catalysis.
AB  - 2-Deoxyribose-5-phosphate aldolase (DERA) catalyzes the reversible conversion of
      acetaldehyde and glyceraldehyde-3-phosphate into deoxyribose-5-phosphate. DERA is
      used as a biocatalyst for the synthesis of drugs such as statins and is a
      promising pharmaceutical target due to its involvement in nucleotide catabolism.
      Despite previous biochemical studies suggesting the catalytic importance of the C
      terminal tyrosine residue found in several bacterial DERAs, the structural and
      functional basis of its participation in catalysis remains elusive because the
      electron density for the last eight to nine residues (i.e., the C-terminal tail)
      is absent in all available crystal structures. Using a combination of NMR
      spectroscopy and molecular dynamics simulations, we conclusively show that the
      rarely studied C-terminal tail of E. coli DERA (ecDERA) is intrinsically
      disordered and exists in equilibrium between open and catalytically relevant
      closed states, where the C-terminal tyrosine (Y259) enters the active site.
      Nuclear Overhauser effect distance restraints, obtained due to the presence of a
      substantial closed state population, were used to derive the solution-state
      structure of the ecDERA closed state. Real-time NMR hydrogen/deuterium exchange
      experiments reveal that Y259 is required for efficiency of the proton abstraction
      step of the catalytic reaction. Phosphate titration experiments show that, in
      addition to the phosphate-binding residues located near the active site, as
      observed in the available crystal structures, ecDERA contains previously unknown
      auxiliary phosphate-binding residues on the C-terminal tail which could
      facilitate in orienting Y259 in an optimal position for catalysis. Thus, we
      present significant insights into the structural and mechanistic importance of
      the ecDERA C-terminal tail and illustrate the role of conformational sampling in
      enzyme catalysis.

PMID- 30101039
TI  - Natural History of Uterine Fibroids: A Radiological Perspective.
AB  - Purpose of Review: This review aims to update our understanding of the
      radiological life cycle of fibroids, so that we may better counsel patients
      making difficult treatment decisions. Evidence for both pregnant and non-pregnant
      women have been considered separately. Recent Findings: Recent findings have
      shown that fibroids can undergo both growth and regression in non-gravid uterus.
      In pregnant women, fibroid growth is non-linear fashion, with the greatest growth
      occurring in the first 7 weeks of pregnancy. Growth in the later trimesters was
      significantly slower. Summary: Fibroid growth, both in the intra- and inter
      gravid states, is variable and can range from 18 to 120% per year. In the inter
      gravid state, fibroids can grow or undergo spontaneous regression. Factors that
      can predict fibroid growth include the starting volume of fibroid, type of
      fibroid and age of patient. In the gravid state, fibroids appears to grow in a
      non-linear pattern, with the most rapid growth occurring in the first trimester.
      Factors affecting fibroid growth in pregnancy include the size of fibroids and
      number of fibroids.

PMID- 30101040
TI  - Good girls and boys: findings from a cross-sectional survey on adolescent rights,
      relationships, and sexuality in an urban informal settlement in India.
AB  - Around 20% of India's population are adolescents aged 10-19 years. Our objective
      was to strengthen program interventions on gender equity, health, and
      participation by gauging adolescents' levels of understanding and opinions. In a
      cross-sectional survey, we interviewed 2005 adolescents on their opinions on
      rights, friendship and sex, sexual refusal and coercion, and communication with
      family, using a two-stage probability proportional to size sample. Opinions on
      gender allocations were generally equitable, although females supported clothing
      proscriptions. Premarital sex, multiple partners, masturbation and non
      heterosexual partnerships were frowned upon. Few respondents said that they felt
      pressure to be sexually active, 79% said that sexual coercion was a form of
      violence, but 14% of older adolescents said that it would be unreasonable to
      refuse sex. Our interviews described young people negotiating the terrain between
      perceived normative expectations and contemporary aspirations, showing limited
      manoeuvring within assumed gender roles in which family control was prominent.

PMID- 30101041
TI  - Lateral Eye Movements Increase False Memory Rates.
AB  - Eye movement desensitization and reprocessing (EMDR) is a popular treatment for
      posttraumatic stress disorder. However, little is known about the memory effects
      of EMDR. Using a misinformation paradigm, we examined whether lateral eye
      movements, as used in EMDR, enhance susceptibility to false memories.
      Undergraduates (N = 82) saw a video depicting a car crash. Subsequently,
      participants either performed eye movements or held their eyes stationary.
      Afterward, all participants received misinformation in the form of an eyewitness
      narrative. The results indicate that eye movement participants were less accurate
      and were more susceptible to the misinformation effect than controls. Our finding
      suggests EMDR may have risky drawbacks in an eyewitness context and therefore
      urgently needs follow-up research.

PMID- 30101042
TI  - The H Syndrome: A Genodermatosis.
AB  - H syndrome (histiocytosis lymph adenopathy plus syndrome) is an autosomal
      recessive disorder caused by mutations in the SLC29A3 gene, encoding the human
      equilibrative nucleoside transporter (hENT3), characterized by cutaneous
      hyperpigmentation and hypertrichosis, hepatosplenomegaly, hearing loss, heart
      anomalies, hypogonadism, low height, hyperglycemia/insulin-dependent diabetes
      mellitus, and hallux valgus/flexion contractures. Exophthalmos, malabsorption,
      renal anomalies, flexion contractions of interphalangeal joints and hallux
      valgus, and lytic bone lesions, as well as osteosclerosis, are also seen. If
      these are lacking, the constellation of additional findings should raise
      suspicion for H syndrome. As most of the patients reported to date with H
      syndrome are from traditional, low-income populations, where consanguinity is
      common, it is highly important to develop a cheap and affordable technique for a
      mutation analysis. Two siblings presented to us, diagnosed as having insulin
      dependent diabetes mellitus (IDDM) since the age of eight years and progressive
      flexion contracture of the small joints for seven-eight years. On examination,
      both had short stature. One also had bilateral cervical lymphadenopathy. The
      female had the Tanner stage of B3P3A2 M0 and the male had the Tanner stage of
      prepuberty. Laboratory workup, including antinuclear antibodies, rheumatoid
      factor, erythrocyte sedimentation rate, thyroid profile, and Celiac serology were
      negative. Genetic studies confirmed the diagnosis of H syndrome.

PMID- 30101043
TI  - Left Atrial Myxoma Embolization Presenting as Acute Limb Ischemia: An Unusual
      Presentation.
AB  - Cardiac myxomas are rare with reported incidences of less than 0.03%. Cardiac
      myxomas are most commonly observed in the left atrium. Their clinical
      manifestations vary and most are non-specific to the diagnosis. The most common
      extra-cardiac manifestations are thrombo-embolic infarcts from tumor
      embolization. A previously healthy 55-year-old man presented with findings
      suggestive of acute arterial limb ischemia. Following surgical treatment of his
      acute presentation, a left atrial mass was found on echocardiography suggesting
      that the embolization was secondary to a cardiac myxoma. The patient was
      discharged without complication. Embolic myxoma should be included in the
      differential in younger, previously healthy patients presenting with acute
      arterial limb ischemia without obvious cause. Our patient's dramatic presentation
      with a single acute event, however, prompted immediate treatment and resulted in
      a functional recovery with minimal complications.

PMID- 30101044
TI  - Graves' Disease Presenting as Painful Goiter: A Case Report and Review of the
      Literature.
AB  - A painful and tender thyroid gland is a rare phenomenon in Graves' disease. We
      present a case of 31-years-old Guyanese female who was admitted to the hospital
      with complaints of neck pain for the past few days. She also reported increase
      appetite for a few weeks; she did not have palpitations, heat intolerance, or
      muscle weakness. The presence of hyperthyroidism with elevated TSI suggested that
      the patient had Graves' disease. Erythrocyte sedimentation rate (ESR) and C
      reactive protein (CRP) were within normal limit, thus the diagnosis of
      thyroiditis was effectively ruled out. This is a rare case of a painful and
      tender thyroid gland in Graves' disease without the evidence of sub-acute
      thyroiditis.

PMID- 30101045
TI  - Does Subclinical Hypothyroidism Affect Hospitalization Outcomes and Mortality in
      Congestive Cardiac Failure Patients?
AB  - Objective This study aimed to determine the differences in hospitalization
      outcomes among patients admitted for congestive cardiac failure (CCF) with
      underlying subclinical hypothyroidism (SCH). Methods This retrospective case
      control study used data from the nationwide inpatient sample (NIS) for the years
      2012-2014. We identified cases with CCF as the primary diagnosis and SCH as the
      secondary diagnosis using validated ICD-9-CM codes and controls with CCF only.
      The differences in hospitalization outcomes and hospital characteristics were
      quantified using the multinomial logistic regression model (adjusted odds ratio
      (aOR)). Results A total of 143,735 CCF patients were enrolled in this study, and
      73,440 cases had IH. About 31.8% of SCH patients were hospitalized for more than
      four days (median) compared to 44.7% patients without SCH (P < .001). The median
      hospitalization charges per admission for CCF was $20,312. CCF patients with SCH
      had lower odds of longer hospitalization (aOR = .709, 95% CI .660-.762, P < .001)
      and higher hospitalization charges (aOR = .783, 95% CI .728-.841, P < .001)
      compared to CCF patients without SCH. CCF patients with SCH had two times higher
      odds of minor morbidity (aOR = 2.276; 95% CI 2.105-2.462; P < .001) but lower
      odds of major morbidity (aOR = .783; 95% CI .728-.841; P < .001). Inpatient
      mortality with SCH patients (2%) compared to 3.6% patients without SCH (P <
      .001). CCF patients with SCH had lower odds of in-hospital mortality (aOR = .547;
      95% CI .496-.604; P < .001). CCF patients with SCH had higher odds of being seen
      in rural non-teaching hospitals (aOR = 1.696; 95% CI 1.572-1.831; P < .001).
      Also, CCF patients with SCH had the highest likelihood of presence in the western
      region of the United States (aOR = 149.924; 95% CI 110.497-203.419; P < .001)
      followed by the southern region (aOR = 31.431; 95% CI 26.066-37.900; P < .001).
      Conclusions Among CCF with SCH patients during hospitalization, we observed a
      variation in hospitalization outcomes, including inpatient length of stay and
      cost, morbidity, and in-hospital mortality. We found no significant increase in
      mortality and major morbidity in CCF patients with SCH. There were differences in
      the hospital characteristics between CCF patients with and without SCH. Thus,
      hospital bed size, location, and teaching status act as predictors for a co
      diagnosis of SCH in CCF. Further research is needed to guide the development of
      clinical care models for targeting early diagnosis and treatment to determine
      whether thyroid hormone replacement would be beneficial for CCF patients with SCH
      and improve quality of care in these patients.

PMID- 30101046
TI  - Colovesical Fistula As An Uncommon Presentation Of Metastatic Lung Cancer.
AB  - Colovesical fistula is an atypical communication between the colon and the
      bladder. The most common causes of colovesical fistula are diverticulitis,
      inflammatory bowel disease, lymphoma and complication from radiation therapy.
      Patients with colovesical fistula present with recurrent urinary tract infections
      (UTI), dysuria, frequency, abdominal pain, pneumaturia, faecaluria, and
      hematuria. We present a case of a patient with stage IV lung adenocarcinoma
      presented with abdominal pain, dysuria, and faecaluria who was found to have a
      colovesical fistula. Although colovesical fistula may be sequelae of advanced
      colon or bladder cancer, it is a very uncommon presentation of metastatic cancer
      from distant sites. Our case is the first to show that colovesical fistula may
      present from metastatic lung adenocarcinoma. Clinical awareness of this very
      unusual presentation of metastatic cancer can lead to faster diagnosis and
      treatment, possibly minimizing excessive use of antibiotics.

PMID- 30101047
TI  - Portal Hypertension and a Stiff Liver.
AB  - Portal hypertension (PH) is a common clinical syndrome leading to severe
      complications. In the western world, about 90% of cases of PH are due to liver
      cirrhosis, and thanks to the availability of ultrasound elastography methods,
      this diagnosis is usually confirmed at bedside. We report a case of a patient
      presenting with PH and ascites initially suspected of suffering from liver
      cirrhosis. The finding of large hepatomegaly and a massive increase in liver
      stiffness prompted us to perform a liver biopsy. This revealed no fibrosis, but
      diffuse primary amyloidosis (AL amyloidosis). We discuss the diagnostic and
      treatment of this case, with emphasis on non-invasive imaging methods available
      for diagnosis and follow up.

PMID- 30101048
TI  - Subcutaneous Heparin Leads to Rectus Sheath Hematoma: A Rare Complication.
AB  - Rectus sheath hematoma (RSH) is a rare complication that usually occurs in
      patients receiving anticoagulation therapy. It can mimic an acute abdomen and be
      life-threatening. RSH can develop even with prophylactic dose of heparin. Early
      recognition is necessary to decrease morbidity and mortality. RSH should be
      considered in anticoagulated patients who develop sudden onset of abdominal pain.
      RSH is usually managed conservatively, but sometimes requires surgery. Patients
      who are taking antiplatelet require careful monitoring with the use of
      anticoagulation (AC). It is important to identify them early. This is a case of
      69-year-old female who presented with epigastric pain secondary to rectus sheath
      hematoma. She was receiving subcutaneous injections of heparin for left lower
      quadrant pain and swelling for venous thromboembolism prophylaxis. Ultrasound of
      abdomen revealed large rectus sheath hematoma.

PMID- 30101049
TI  - An Unusual Case of Noncatamenial Recurrent Pneumothorax.
AB  - In a 28-year-old female, seven recurrent pneumothoraces occurred during a period
      of 2 years despite multiple thoracic interventions, all on the left thoracic
      side. Despite profound differential diagnostic analysis, the underlying cause
      remains unclear. An accumulation of conditions in this patient affecting only the
      left half of the body is remarkable: sinistral glaucoma as an infant, a sinistral
      pigmentation disorder, and a sinistral Bochdalek hernia.

PMID- 30101050
TI  - Cleaning and disinfection of surfaces in hospitals. Improvement in quality of
      structure, process and outcome in the hospitals in Frankfurt/Main, Germany, in
      2016 compared to 2014.
AB  - The cleaning and disinfection of surfaces in hospitals is becoming increasingly
      important in the multi-barrier approach for preventing infection, in addition to
      hand hygiene and proper reprocessing of medical devices. Therefore, in 2014, the
      quality of structure, process and outcome of surface preparation was checked in
      all hospitals in Frankfurt/Main, Germany. Because of great need for improvements,
      this monitoring was repeated in 2016. The data are presented in comparison to
      those in 2014. Methods: All 16 hospitals provided information on the quality of
      structure. Data on quality of process was obtained through direct observation
      during cleaning and disinfection of rooms and their bathrooms. Data on quality of
      result was acquired using the fluorescence method, i.e., marking surfaces with a
      fluorescent liquid and testing whether this mark has been sufficiently removed by
      cleaning. The results are compared to those of the 17 hospitals monitored in
      2014, before the closing of one of the hospitals.Results: Quality of structure
      [data from 2014]: In all hospitals, the employees were trained regularly. In 14
      (88%) [12; 71%] of those, the foremen had the required qualifications. In 1 (6%)
      [6; 35%] hospitals, some uncertainty remained concerning the interface of the
      cleaning and nursing care services. A complete cleaning was reported to take
      place in 12 (75%) [12; 70%] hospitals on Saturdays and in 4 (25%) [2; 11%]
      hospitals on Sundays. Quality of process: During process monitoring, the
      different surfaces with frequent hand or skin contact were prepared to different
      extents (91-100%) [70-100%]. Quality of result: 88% [75%] of fluorescent marks
      were appropriately removed. Conclusion: Compared to 2014, a clear improvement
      were seen in 2016, especially in the qualification of the foremen and in terms of
      clearly defining the interface between cleaning and care services as well as the
      quality of process and outcome. Nevertheless, regarding the growing importance of
      proper reprocessing of hospital surfaces for prevention of infections and/or
      colonizations, further improvements are mandatory, including a program for better
      education of the cleaning staff.

PMID- 30101052
TI  - Monolithic nano-porous polymer in microfluidic channels for lab-chip liquid
      chromatography.
AB  - In this paper, a nano-porous polymer has been integrated into the microfluidics
      device as on-chip monolithic liquid chromatography column for separation of
      chemical and biological samples. Monolithic nano-porous polymer (MNP) was formed
      and firmly grafted on the surface of the microfluidic channel. Neurotransmitters,
      5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptamine (serotonin, 5-HT),
      were successfully separated with the developed on-chip MNP column.

PMID- 30101053
TI  - Hybrid dielectrics composed of Al2O3 and phosphonic acid self-assembled
      monolayers for performance improvement in low voltage organic field effect
      transistors.
AB  - Low voltage operational organic transistors (< 4 V) based on pentacene were
      successfully fabricated with hybrid dielectric films composed of aluminum oxide
      using atomic layer deposition and various phosphonic acid-based self-assembled
      monolayers as the gate dielectrics. High capacitances up to 279 nF/cm2, low
      leakage current densities of 10-8 A/cm2 at 6 V, and high breakdown fields up to
      7.5 MV/cm were obtained. The transistors with the octadecylphosphonic acid hybrid
      dielectric exhibited an improved saturation mobility of 0.58 cm2/Vs, a
      subthreshold slope of 151 mV/decade, a threshold voltage of - 1.84 V and an on
      off current ratio of 106. The low surface energies of the self-assembled
      monolayers having non-polar terminal groups, such as methyl and
      pentafluorophenoxy, improved the carrier conduction of the transistors due to the
      pentacene growth with an edge-on orientation for low voltage operation. The
      pentafluorophenoxy end-group showed an accumulation of holes at the semiconductor
      dielectric interface.

PMID- 30101051
TI  - Involvement of high-valent manganese-oxo intermediates in oxidation reactions:
      realisation in nature, nano and molecular systems.
AB  - Manganese plays multiple role in many biological redox reactions in which it
      exists in different oxidation states from Mn(II) to Mn(IV). Among them the high
      valent manganese-oxo intermediate plays important role in the activity of certain
      enzymes and lessons from the natural system provide inspiration for new
      developments of artificial systems for a sustainable energy supply and various
      organic conversions. This review describes recent advances and key lessons
      learned from the nature on high-valent Mn-oxo intermediates. Also we focus on the
      elemental science developed from the natural system, how the novel strategies are
      realised in nano particles and molecular sites at heterogeneous and homogeneous
      reaction conditions respectively. Finally, perspectives on the utilisation of the
      high-valent manganese-oxo species towards other organic reactions are proposed.

PMID- 30101054
TI  - Histone H3 Mutations in Cancer.
AB  - Histone modifications are one form of epigenetic information that relate closely
      to gene regulation. Aberrant histone methylation caused by alteration in
      chromatin-modifying enzymes has long been implicated in cancers. More recently,
      recurrent histone mutations have been identified in multiple cancers and have
      been shown to impede histone methylation. All three histone mutations (H3K27M,
      H3K36M, and H3G34V/R) identified result in amino acid substitution at/near a
      lysine residue that is a target of methylation. In the cases of H3K27M and
      H3K36M, found in pediatric DIPG (diffuse intrinsic pontine glioma) and
      chondroblastoma respectively, expression of the mutant histone leads to global
      reduction of histone methylation at the respective lysine residue. These mutant
      histones are termed "oncohistones" because their expression reprograms the
      epigenome and shapes an oncogenic transcriptome. Dissecting the mechanism of
      H3K27M-driven oncogenesis has led to the discovery of promising therapeutic
      targets in pediatric DIPG. The purpose of this review is to summarize the work
      done on identifying and dissecting the oncogenic properties of histone H3
      mutations.

PMID- 30101055
TI  - Aspergillus hepatic artery thrombosis in liver transplantation.
AB  - We present the first cirrhotic patient who underwent liver transplantation (LT)
      and presented a hepatic artery thrombosis of the graft due to Aspergillus
      fumigatus, within the first month of LT. This culminated in graft loss, re
      transplant with multiple biliary and infectious complications. To our knowledge,
      this is a case report of an early hepatic artery thrombosis due to Aspergillus
      fumigatus in an infection-free patient.

PMID- 30101056
TI  - Tension hydropneumothorax as the initial presentation of Boerhaave syndrome.
AB  - Boerhaave syndrome, a rare yet frequently fatal diagnosis, is characterized by
      the spontaneous transmural rupture of the esophagus. The classic presentation of
      Boerhaave syndrome is characterized by Mackler's triad, consisting of chest pain,
      vomiting, and subcutaneous emphysema. However, Boerhaave syndrome rarely presents
      with all the features of Mackler's triad; instead, the common presentation of
      Boerhaave syndrome includes chest or epigastric pain, severe retching and
      vomiting, dyspnea, and shock. These symptoms are typically misdiagnosed as
      cardiogenic in origin. Due to its atypical presentation, rarity, and mimicry of
      emergent conditions, diagnosis of Boerhaave syndrome is often delayed, resulting
      in a high mortality rate at the time of diagnosis and with a subsequent
      exponential increase in mortality if treatment is delayed by greater than 48
      hours. Here, we report two atypical presentations of Boerhaave syndrome
      presenting as tension hydropneumothorax and review ten previously reported cases
      of Boerhaave syndrome presenting as tension hydropneumothorax. This review serves
      to raise clinician awareness about the expansive and elusive ways by which
      esophageal perforation may present, and thereby facilitate timely and potentially
      life-saving diagnosis.

PMID- 30101057
TI  - Co-existence of vocal cord dysfunction with pulmonary conditions other than
      asthma: A case series.
AB  - Background: Vocal cord dysfunction (VCD) is defined as inappropriate movement of
      the vocal cords resulting in functional airway obstruction and symptoms including
      cough, wheezing, and dyspnea. VCD is often misdiagnosed with asthma but can also
      co-exist with asthma. The association of VCD with other serious pulmonary
      conditions has not been described to date. Case reports: We describe the first
      case series of two adult patients evaluated at a university asthma clinic who in
      addition to having VCD also had significant pulmonary pathology other than
      asthma. Patient 1 had VCD and pulmonary veno-occulsive disease which necessitated
      a lung transplant. Patient 2 had VCD and a patent ductus arteriosis who
      necessitated surgical closure. Conclusion: It is important to recognize that VCD
      can exist with pulmonary conditions other than asthma. Lack of improvement in
      respiratory symptoms after appropriate treatment for VCD should alert the
      clinician to evaluate for additional conditions.

PMID- 30101058
TI  - Neurodevelopmental changes in the relationship between stress perception and
      prefrontal-amygdala functional circuitry.
AB  - Our brain during distinct developmental phases may show differential responses to
      perceived psychological stress, yet existing research specifically examining
      neurodevelopmental changes in stress processing is scarce. To fill in this
      research gap, this functional magnetic resonance imaging (fMRI) study examined
      the relationship between perceived stress and resting-state neural connectivity
      patterns among 67 healthy volunteers belonging to three age groups (adolescents,
      young adults and adults), who were supposed to be at separate neurodevelopmental
      phases and exhibit different affect regulatory processes in the brain. While the
      groups showed no significant difference in self-reported general perceived stress
      levels, the functional connectivity between amygdala and ventromedial prefrontal
      cortex (vmPFC) was positively and negatively correlated with perceived stress in
      adolescents and young adults respectively, while no significant correlations were
      observed in adults. Furthermore, among adolescents, the causal functional
      interaction between amygdala and vmPFC exhibited bottom-up connectivity, and that
      between amygdala and subgenual anterior cingulate cortex exhibited top-down
      connectivity, both of which changed to bilateral directions, i.e. both bottom-up
      and top-down connections, in both young adults and adults, supporting the notion
      that the amygdala and prefrontal cortical circuitries undergo functional
      reorganizations during brain development. These novel findings have important
      clinical implications in treating stress-related affective disorders in young
      individuals.

PMID- 30101060
TI  - Left lateralized cerebral glucose metabolism declines in amyloid-beta positive
      persons with mild cognitive impairment.
AB  - Background: Previous publications indicate that Alzheimer's Disease (AD) related
      cortical atrophy may develop in asymmetric patterns, with accentuation of the
      left hemisphere. Since fluorodeoxyglucose positron emission tomography (FDG PET)
      measurements of the regional cerebral metabolic rate of glucose (rCMRgl) provide
      a sensitive and specific marker of neurodegenerative disease progression, we
      sought to investigate the longitudinal pattern of rCMRgl in amyloid-positive
      persons with mild cognitive impairment (MCI) and dementia, hypothesizing
      asymmetric declines of cerebral glucose metabolism. Methods: Using florbetapir
      PET and cerebrospinal fluid (CSF) measures to define amyloid-beta (Abeta)
      positivity, 40 Abeta negative (Abeta-) cognitively unimpaired controls (CU; 76 +/
      5y), 76 Abeta positive (Abeta+) persons with MCI (76 +/- 7y) and 51 Abeta +
      persons with probable AD dementia (75 +/- 7y) from the AD Neuroimaging Initiative
      (ADNI) were included in this study with baseline and 2-year follow-up FDG PET
      scans. The degree of lateralization of longitudinal rCMRgl declines in subjects
      with Abeta + MCI and AD in comparison with Abeta- CU were statistically
      quantified via bootstrapped lateralization indices [(LI); range - 1 (right) to 1
      (left)]. Results: Compared to Abeta- CU, Abeta + MCI patients showed marked left
      hemispheric lateralization (LI: 0.78). In contrast, modest right hemispheric
      lateralization (LI: -0.33) of rCMRgl declines was found in Abeta + persons with
      probable AD dementia. Additional comparisons of Abeta + groups (i.e. MCI and
      probable AD dementia) consequently indicated right hemispheric lateralization
      (LI: -0.79) of stronger rCMRgl declines in dementia stages of AD. For all
      comparisons, voxel-based analyses confirmed significant (pFWE<0.05) declines of
      rCMRgl within AD-typical brain regions. Analyses of cognitive data yielded
      predominant decline of memory functions in both MCI and dementia stages of AD.
      Conclusions: These data indicate that in early stages, AD may be characterized by
      a more lateralized pattern of left hemispheric rCMRgl declines. However,
      metabolic differences between hemispheres appear to diminish with further
      progression of the disease.

PMID- 30101059
TI  - Relationship between sensorimotor cortical activation as assessed by functional
      near infrared spectroscopy and lower extremity motor coordination in bilateral
      cerebral palsy.
AB  - Background: Evaluation of task-evoked cortical responses during movement has been
      limited in individuals with bilateral cerebral palsy (CP), despite documented
      alterations in brain structure/function and deficits in motor control. Objective:
      To systematically evaluate cortical activity associated with lower extremity
      tasks, and relate activation parameters to clinical measures in CP. Methods: 28
      ambulatory participants (14 with bilateral CP and 14 with typical development)
      completed five motor tasks (non-dominant ankle dorsiflexion, hip flexion and leg
      cycling as well as bilateral dorsiflexion and cycling) in a block design while
      their sensorimotor cortex was monitored using functional near infrared
      spectroscopy (fNIRS), in addition to laboratory and clinical measures of
      performance. Results: Main effects for group and task were found for extent of
      fNIRS activation (number of active channels; p < 0.001 and p = 0.010,
      respectively), magnitude of activation (sum of beta values; p < 0.001 for both),
      and number of active muscles (p = 0.001 and p < 0.001, respectively), but no
      group by task interactions. Collectively, subgroups with CP and especially those
      with greater impairments, showed higher extent and magnitude of cortical
      sensorimotor activation as well as higher amounts of concurrent activity in
      muscles not required for task performance. Magnitude of fNIRS activation during
      non-dominant dorsiflexion correlated with validated measures of selective control
      (r = -0.60, p = 0.03), as well as mobility and daily activity (r = -0.55, p =
      0.04 and r = -0.52, p = 0.05, respectively) and self-reported gait function (r = 
      0.68, p = 0.01) in those with CP. Conclusions: The association between higher
      activity in the sensorimotor cortex and decreased selectivity in cortical
      organization suggests a potential neural mechanism of motor deficits and target
      for intervention.

PMID- 30101061
TI  - Functional and structural connectivity of the amygdala underpins locus of control
      in mild cognitive impairment.
AB  - Locus of control (LOC) is an important personality trait. LOC over cognitive
      competency reflects an individual's perceived control of desired cognitive
      outcomes, which is critical for maintaining successful cognitive aging. It is
      important to understand the neural substrates of LOC over cognitive competency in
      older adults, especially for individuals at high risk of dementia. Here, we
      characterized a cohesive functional and structural connectivity profile
      underlying LOC among 55 older adults with amnestic mild cognitive impairment
      (aMCI), combining resting-state functional magnetic resonance imaging and
      diffusion tensor imaging. The results showed that both functional and structural
      connectivity between the medial prefrontal cortex and amygdala were significantly
      correlated with external LOC. The functional connectivity mediated the
      correlation between structural connectivity and external LOC. In addition, aging
      associated neurodegeneration moderated the relationship between structural
      connectivity and external LOC, showing that the structural connectivity was
      positively correlated with external LOC in low, but not high neurodegeneration.
      Our results suggest a critical role of the functional amygdala-frontal network,
      which may serve as a bridge between its white matter tract and LOC over cognitive
      competency in groups at high risk for dementia.

PMID- 30101064
TI  - Thalamic bacterial abscess presenting with hemiparesis and expressive aphasia.
AB  - Brain abscesses are relative rare in the developing world, with an incidence of
      2% of all space occupying lesions. Deep-seated abscesses such as thalamic and
      basal ganglia abscesses are much rarer than abscesses in other locations of the
      brain, comprising 1.3-6% of all brain abscesses. These abscesses may present with
      hemiparesis, and subcortical aphasia has only been reported in a few cases
      throughout the literature. Here we present and discuss a case of thalamic brain
      abscess caused by S. anginosus that presented with subcortical aphasia.

PMID- 30101062
TI  - Sex-specific hippocampus volume changes in obstructive sleep apnea.
AB  - Introduction: Obstructive sleep apnea (OSA) patients show hippocampal-related
      autonomic and neurological symptoms, including impaired memory and depression,
      which differ by sex, and are mediated in distinct hippocampal subfields.
      Determining sites and extent of hippocampal sub-regional injury in OSA could
      reveal localized structural damage linked with OSA symptoms. Methods: High
      resolution T1-weighted images were collected from 66 newly-diagnosed, untreated
      OSA (mean age +/- SD: 46.3 +/- 8.8 years; mean AHI +/- SD: 34.1 +/- 21.5
      events/h;50 male) and 59 healthy age-matched control (46.8 +/- 9.0 years;38 male)
      participants. We added age-matched controls with T1-weighted scans from two
      datasets (IXI, OASIS-MRI), for 979 controls total (426 male/46.5 +/- 9.9 years).
      We segmented the hippocampus and analyzed surface structure with "FSL FIRST"
      software, scaling volumes for brain size, and evaluated group differences with
      ANCOVA (covariates: total-intracranial-volume, sex; P < .05, corrected). Results:
      In OSA relative to controls, the hippocampus showed small areas larger volume
      bilaterally in CA1 (surface displacement <=0.56 mm), subiculum, and uncus, and
      smaller volume in right posterior CA3/dentate (>= - 0.23 mm). OSA vs. control
      males showed higher bilateral volume (<=0.61 mm) throughout CA1 and subiculum,
      extending to head and tail, with greater right-sided increases; lower bilateral
      volumes (>= - 0.45 mm) appeared in mid- and posterior-CA3/dentate. OSA vs control
      females showed only right-sided effects, with increased CA1 and subiculum/uncus
      volumes (<=0.67 mm), and decreased posterior CA3/dentate volumes (>= - 0.52 mm).
      Unlike males, OSA females showed volume decreases in the right hippocampus head
      and tail. Conclusions: The hippocampus shows lateralized and sex-specific, OSA
      related regional volume differences, which may contribute to sex-related
      expression of symptoms in the sleep disorder. Volume increases suggest
      inflammation and glial activation, whereas volume decreases suggest long-lasting
      neuronal injury; both processes may contribute to dysfunction in OSA.

PMID- 30101065
TI  - Third molar pericoronitis in neutropenia.
AB  - We report the case of a 40 year-old woman who presented third molar pericoronitis
      in neutropenia. she had undergone extraction of the right third mandibular molar.
      This may have been due to an infection in the extraction socket or part of the
      crown. There was no inflammation seen after transplant of umbilical cord blood.

PMID- 30101063
TI  - Structural and functional brain imaging in acute HIV.
AB  - Background: HIV RNA is identified in cerebrospinal fluid (CSF) within eight days
      of estimated viral exposure. Neurological findings and impaired
      neuropsychological testing performance are documented in a subset of individuals
      with acute HIV infection (AHI). The purpose of this study was to determine
      whether microstructural white matter and resting-state functional connectivity
      (rsFC) are disrupted in AHI. Methods: We examined 49 AHI (100% male; mean age =
      30 +/- SD 9.9) and 23 HIV-uninfected Thai participants (78% male; age = 30 +/-
      5.5) with diffusion tensor imaging (DTI) and rsFC acquired at 3 Tesla, and four
      neuropsychological tests (summarized as NPZ-4). MRI for the AHI group was
      performed prior to combination antiretroviral treatment (ART) in 26 participants
      and on average two days (range:1-5) after ART in 23 participants. Fractional
      anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) were
      quantified for DTI. Seed-based voxelwise rsFC analyses were completed for the
      default mode (DMN), fronto-parietal, and salience and 6 subcortical networks.
      rsFC and DTI analyses were corrected for family-wise error, with voxelwise
      comparisons completed using t-tests. Group-specific voxelwise regressions were
      conducted to examine relationships between imaging indices, HIV disease
      variables, and treatment status. Results: The AHI group had a mean (SD) CD4 count
      of 421(234) cells/mm3 plasma HIV RNA of 6.07(1.1) log10 copies/mL and estimated
      duration of infection of 20(5.5) days. Differences between AHI and CO groups did
      not meet statistical significance for DTI metrics. Within the AHI group,
      voxelwise analyses revealed associations between brief exposure to ART and higher
      FA and lower RD and MD bilaterally in the corpus callosum, corona radiata, and
      superior longitudinal fasciculus (p < 0.05). Diffusion indices were unrelated to
      clinical variables or NPZ-4. The AHI group had reduced rsFC between left
      parahippocampal cortex (PHC) of the DMN and left middle frontal gyrus compared to
      CO (p < 0.002). Within AHI, ART status was unrelated to rsFC. However, higher CD4
      cell count associated with increased rsFC for the right lateral parietal and PHC
      seeds in the DMN. Direct associations were noted between NPZ-4 correspond to
      higher rsFC of the bilateral caudate seed (p < 0.002). Conclusions: Study
      findings reveal minimal disruption to structural and functional brain integrity
      in the earliest stages of HIV. Longitudinal studies are needed to determine if
      treatment with ART initiated in AHI is sufficient to prevent the evolution of
      brain dysfunction identified in chronically infected individuals.

PMID- 30101066
TI  - Morbilliform skin rash with prominent involvement of the palms in Chikungunya
      fever.
AB  - An outbreak of chikungunya occurred in Central Italy in the summer of 2017.
      During the outbreak, two siblings with fever and joint pain developed a
      morbilliform skin rash with prominent involvement of the palms. Knowledge of the
      characteristics of chikungunya exanthem is important to adddress clinical
      diagnosis.

PMID- 30101067
TI  - Nocardia paucivorans brain abscess. Clinical and microbiological characteristics.
AB  - Nocardia paucivorans brain abscesses are unusual in humans. Sixteen cases of this
      infection have been reported in the world medical literature. There is precise
      clinical information available from nine patients. All of these patients
      recovered or were cured from their brain disease with long-term antimicrobial
      treatment. Surgical drainage was performed in four patients.

PMID- 30101068
TI  - Acute syphilitic meningitis in an HIV-infected patient.
AB  - We present a case of acute syphilitic meningitis in a 28-year old HIV-infected
      patient, presenting with a seizure. MRI revealed a meningeal lesion with cortical
      involvement, and the patient described previous treatment for syphilis. Final
      diagnosis was established by PCR and spirochete staining on a brain biopsy, upon
      which the patient was successfully treated with benzylpenicillin.

PMID- 30101069
TI  - Microfilaria presenting as nephrotic syndrome in a young female.

PMID- 30101070
TI  - Chronic intestinal pseudo-obstruction due to Strongyloides stercoralis.
AB  - We report a case of chronic intestinal pseudo-obstruction due to a generalized
      visceral autonomic neuropathy in an immune-competent patient infected with
      Strongyloides stercoralis. The patient had immigrated to the United States from
      Sierra Leone in childhood but had not returned for decades. His symptoms resolved
      with ivermectin treatment. Clinicians should have a high index of suspicion for
      strongyloidiasis in any patient with abdominal complaints and a history of travel
      to endemic areas, even if the travel history is remote.

PMID- 30101071
TI  - Newly diagnosed AIDS with neurosyphilis, Kaposi sarcoma, pancytopenia,
      oropharyngeal candidiasis, and pseudomonal pneumonia: We shouldn't be seeing this
      anymore.
AB  - The incidence of new human immunodeficiency virus (HIV) infections is declining
      and is half of what it was in the mid 1990s. We present a case of newly diagnosed
      HIV with acquired immune deficiency syndrome (AIDS), Neurosyphilis, Kaposi
      Sarcoma, and multiple opportunistic infections. Although this type of patient was
      not uncommon in the pre-antiretroviral era, we do not often see such a
      constellation of conditions in a single individual. The significance of this case
      lies not in the diagnosis, but rather in the number of the diagnoses and the
      thought process used to attain them.

PMID- 30101072
TI  - Lactobacillus garvieae endocarditis presenting with leg cramps.
AB  - An 85-year-old man with a history of aortic valve replacement presented with
      lower limb cramps. He was initially diagnosed with degenerative disc disease, but
      was found to have Lactococcus garvieae infective endocarditis with septic embolic
      strokes causing a central poststroke pain syndrome. Cardiothoracic surgery was
      deemed too high risk and the patient completed 6 weeks of intravenous
      antimicrobials as well as prolonged inpatient rehabilitation. Lactococcus
      garvieae is an aquaculture pathogen which typically affects elderly and
      immunocompromised patients. Atypical presentations of endocarditis in the elderly
      can lead to delays in diagnosis.

PMID- 30101075
TI  - Acute scrotum - Torsion of the third testicle!

PMID- 30101074
TI  - Prostatic metastasis from intrahepatic cholangiocarcinoma.

PMID- 30101076
TI  - En-bloc resection of a mixed mesenchymal and stromal tumor from the renal pelvis
      using laparoscopic pyelotomy - A case report.

PMID- 30101077
TI  - Ureteral stent obstruction and stent's discomfort are not irreparable damages.
AB  - Ureteral stent obstruction is a significant cause of morbidity and mortality from
      renal failure. Alternative options for decompression include tandem ureteral
      stents but the amount of material in the bladder may severely impair the quality
      of life. Following recurrent stent obstruction, a patient was fitted with tandem
      ureteral stent on both sides with a new nonrefluxing silicone end piece. After
      this procedure, renal function was improved with normal serum creatinine. The
      design of the new stent demonstrates the feasibility of the procedure. This new
      stent currently under prospective evaluation with tolerance questionnaire has
      demonstrated quite promising results in 10 patients.

PMID- 30101078
TI  - About a spontaneous rupture of a renal artery aneurysm.

PMID- 30101079
TI  - Narratives of meaningful endurance - how migrant women escape the vicious cycle
      between health problems and unemployment.
AB  - Migrant women in Europe have a higher incidence of health problems and have
      disproportionately high unemployment rates. We examine how Dutch and Turkish,
      Moroccan and Surinamese first and second generation migrant women escape the
      vicious cycle between health problems and unemployment by using the theory of the
      Sense of Coherence (SOC). We study how SOC works and whether SOC is also
      applicable outside the domain of health. Our findings from life story interviews
      (N = 54) show that women can escape this vicious cycle through the meaningful
      reconstruction of adversity. Women can put a halt on the on-going negative chain
      reaction through focusing on the meaning and purpose of adversity. We name such
      life stories narratives of meaningful endurance, which are characterized by
      structure, authorship and meaningful reconstruction, in opposition to its
      counterpart, narratives of non-directional distress. The three respective
      components of SOC - comprehensibility, manageability and meaningfulness - enable
      the attainment of a narrative of meaningful endurance and individuals with a
      stronger SOC are more likely to tell narratives of meaningful endurance.
      Theoretical and policy implications of our findings are discussed.

PMID- 30101080
TI  - Shifting vulnerabilities: gender and reproductive care on the migrant trail to
      Europe.
AB  - The reproductive care of pregnant migrants entering the European Union via its
      Mediterranean borders represents an under-examined topic, despite a growing
      scholarly emphasis on female migrants and the gendered aspects of migration in
      the past three decades. This article uses ethnographic data gathered in Greece,
      Italy, and Spain to examine pregnant migrants' experiences of crossing, first
      reception, and reproductive care. We discuss our findings through the conceptual
      lens of vulnerability, which we understand as a shifting and relational condition
      attributed to, or dynamically endorsed by, migrant patients within given social
      contexts and encounters. We focus on two principal aspects of migrant women's
      experiences. First, we shed light on their profiles, their journeys to Europe via
      the three main Mediterranean routes, and the conditions of first reception.
      Through ethnographic vignettes we examine the diverse ways in which pregnant
      migrants become vulnerable within these contexts. Second, we turn to the
      reproductive healthcare they receive in EU borderlands. We explore how
      declinations of ideas of vulnerability shape the medical encounter between
      healthcare professionals and migrant women and how vulnerability is dynamically
      used or contested by migrant patients to engage in meaningful social relations in
      unpredictable and unstable borderlands.

PMID- 30101073
TI  - Early feeding practices in infants with phenylketonuria across Europe.
AB  - Background: In infants with phenylketonuria (PKU), dietary management is based on
      lowering and titrating phenylalanine (Phe) intake from breast milk or standard
      infant formula in combination with a Phe-free infant formula in order to maintain
      blood Phe levels within target range. Professionals use different methods to feed
      infants with PKU and our survey aimed to document practices across Europe.
      Methods: We sent a cross sectional, survey monkey(r) questionnaire to European
      health professionals working in IMD. It contained 31 open and multiple-choice
      questions. The results were analysed according to different geographical regions.
      Results: Ninety-five centres from 21 countries responded. Over 60% of centres
      commenced diet in infants by age 10 days, with 58% of centres implementing
      newborn screening by day 3 post birth. At diagnosis, infant hospital admission
      occurred in 61% of metabolic centres, mainly in Eastern, Western and Southern
      Europe. Breastfeeding fell sharply following diagnosis with only 30% of women
      still breast feeding at 6 months.53% of centres gave pre-measured Phe-free infant
      formula before each breast feed and 23% alternated breast feeds with Phe-free
      infant formula. With standard infant formula feeds, measured amounts were
      followed by Phe-free infant formula to satiety in 37% of centres (n = 35/95),
      whereas 44% (n = 42/95) advised mixing both formulas together. Weaning commenced
      between 17 and 26 weeks in 85% centres, >=26 weeks in 12% and < 17 weeks in 3%.
      Discussion: This is the largest European survey completed on PKU infant feeding
      practices. It is evident that practices varied widely across Europe, and the
      practicalities of infant feeding in PKU received little focus in the PKU European
      Guidelines (2017). There are few reports comparing different feeding techniques
      with blood Phe control, Phe fluctuations and growth. Controlled prospective
      studies are necessary to assess how different infant feeding practices may
      influence longer term feeding development.

PMID- 30101082
TI  - An allied approach for in vitro modulation of aldose reductase, sorbitol
      accumulation and advanced glycation end products by flavonoid rich extract of
      Coriandrum sativum L. seeds.
AB  - Traditional herbal medicines are attaining more popularity and are being widely
      practiced. Coriandrum sativum L. is one of the oldest herbal medicinal plants
      valued for its nutritional and medicinal properties. Present investigation was
      focussed on evaluation of attenuating potential of flavonoid rich extract of C.
      sativum (FCS) seeds against pathogenic markers of diabetic complications i.e.
      advanced glycation end products (AGEs), sorbitol and aldose reductase (ALR); by
      using in-vitro methods. Gas chromatography-mass spectrometry (GC-MS) and Infrared
      spectroscopy of FCS revealed the presence of different flavonoids. Results
      demonstrated that FCS has produced 79.80% inhibition of AGEs formation.
      Additionally, FCS was effective against sorbitol accumulation and ALR inhibition
      with IC50 values of 221 MUg/ml and 6.08 MUg/ml respectively. Molecular docking
      was conducted against three binding site for ALR, RAGEs and sorbitol
      dehydrogenase to explore their binding interactions with identified flavonoids.
      The constituents F2, F4 and F6 have shown good binding interactions with all the
      receptors. The visualisation of the docked complexes revealed the occurrence of
      hydrophobic forces and hydrogen bonding in receptor and docked constituents. The
      results were in support with experimental inhibitory activities of FCS against
      these biomarkers and provide a considerable basis for the identification and
      development of new inhibitors.

PMID- 30101083
TI  - HPTLC - Bioautographic methods for selective detection of the antioxidant and
      alpha-amylase inhibitory activity in plant extracts.
AB  - A high-performance thin-layer chromatography (HPTLC) method was developed for
      quantification of alpha-amylase inhibitory activity and stigmasterol content in
      ant plant extracts. An improved HPTLC method for the determination of total free
      radical scavenging activity in samples using DPPH* is also reported. For
      quantification of alpha-amylase inhibitory activity, the developed HPTLC plate is
      dipped into an alpha-amylase solution, and the bioautogram is then incubated at
      25  degrees C for 30 min under humid conditions. For visualization of enzyme
      inhibitory activity, the starch test with an iodine indicator solution is used.
      The blue zone observed comes from the starch-iodine complex formed from starch
      that was not hydrolyzed by the amylase due to enzyme inhibition by the
      compound(s) present in the sample. The area of the blue zones was used to compare
      and quantify relative alpha-amylase inhibitory activity in different extracts.
      Location of the blue zones (hRF) on the plate was used to detect compounds that
      are responsible for the alpha-amylase inhibitory activity. Relative alpha-amylase
      activity was not related to the antioxidant activity, but was highly correlated
      with the stigmasterol content in the sample extracts (R = 0.95). Therefore, plant
      sterols present in the extracts might be responsible for alpha-amylase inhibitory
      activities in the extracts. *The developed method for quantification of alpha
      amylase inhibitory activity provides an efficient and effective tool that can be
      used to screen, detect and quantify alpha-amylase inhibitory activity in plant
      extracts.*The proposed protocol is easy to run, involves minimal sample
      preparation, with multiple samples able to be analyzed in parallel on the same
      chromatographic plate, in a short time.*There were significant differences in
      alpha-amylase inhibitory activity, stigmasterol content, and total free radical
      scavenging activity between methanol, ethanol, dichloromethane, and ethyl acetate
      ant plant extracts.

PMID- 30101081
TI  - Aflatoxin B1 residues in human livers and their relationship with markers of
      hepatic carcinogenesis in Sao Paulo, Brazil.
AB  - In this study, hepatic biopsies from autopsy cases in Sao Paulo, Brazil, showing
      hepatocellular carcinoma (HCC, n = 8), cirrhosis associated with viral hepatitis
      (VC, n = 20), cirrhosis associated with alcoholism (AC, n = 20), and normal
      livers (NL or controls, n = 10) were subjected to determination of aflatoxin B1
      (AFB1) and its main metabolites, and of markers of hepatic carcinogenesis Only
      non-metabolized AFB1 was detected in 13 samples (27.1%, N = 48) of liver
      disorders (HCC, VC and AC), at levels between 10.0 and 418.0 pg/g (mean: 76.6 +/-
      107.7 pg/g). Immuno-labeling of p53, cyclin D1, p21, beta-catenin, and Prohibitin
      (PB) increased mainly in HCC patients, in relation to the controls. AFB1+ samples
      of HCC presented higher expressions of p53, cyclin D1, p21, and beta-catenin
      compared with AFB1-livers. In contrast, p27, p16, and Rb immuno-labeling
      decreased in HCC, VC, and AC samples, compared with NL, with lowest values in
      AFB1+ samples for all liver disorders. Compared with NL, gene expression of
      cyclin D1 and PB in AFB1+ samples of HCC and AC were also higher, along with
      higher gene expression of p21 in VC and AC AFB1+ livers. Results indicated that
      patients with liver disorders were exposed to dietary aflatoxins, and that
      residual AFB1 in liver negatively affected the p53 and protein Rb pathways in
      HCC. Moreover, the presence of AFB1 in cirrhotic livers warrants concern about
      the potential contribution of dietary aflatoxin to disease progression during VC
      and AC.

PMID- 30101084
TI  - Anesthesia of the geriatric equine.
AB  - Advancements in veterinary medicine have resulted in an increased number of
      geriatric horses being presented for medical or surgical procedures that require
      general anesthesia. Due to the physiological changes associated with aging and
      the likelihood of concurrent disease conditions, the geriatric equine is at an
      increased risk during anesthesia. The main physiological changes associated with
      aging, and their impact on anesthesia, are discussed in this review.

PMID- 30101086
TI  - Supplementing five-point body condition score with body fat percentage increases
      the sensitivity for assessing overweight status of small to medium sized dogs.
AB  - Background and methods: Currently, five-point body condition scoring (BCS) is
      widely used by veterinarians and clinicians to assess adiposity in dogs in Japan.
      However, BCS score assignment is subjective in nature, and most clinicians do not
      score with half points, instead preferring to round off values, thereby rendering
      less accurate assessments. Therefore, we sought to determine whether assessing
      body fat percentage using simple morphometric measurements and supplementing this
      with five-point BCS can have increased sensitivity for detecting increasing
      adiposity in overweight small-medium sized dog breeds via plasma metabolite
      validation. Results: Overall, lean body fat percentage was determined to be 15%
      22% for male (non-neutered/neutered) dogs and 15%-25% for female
      (nonspayed/spayed). Dogs categorized as overweight by BCS had significantly
      higher levels of nonesterified fatty acids (P = 0.005), whereas animals
      categorized as overweight by BCS + body fat percentage were observed to have
      significantly higher levels of nonesterified fatty acids (P = 0.006), total
      cholesterol (P = 0.029), and triglycerides (P = 0.001) than lean animals. The
      increased sensitivity due to body fat percentage for gauging alterations in
      plasma metabolite levels may be due to increased correlation strength. Body fat
      percentage correlated positively with plasma insulin (r = 0.627, P = 0.002),
      nonesterified fatty acids (r = 0.674, P < 0.001), total cholesterol (r = 0.825, P
      < 0.0001), triglycerides (r = 0.5823, P < 0.005), blood urea nitrogen (r = 0.429,
      P < 0.05), creatinine (r = 0.490, P = 0.021), and total protein (r = 0.737, P <
      0.0001) levels, which all tend to increase as a result of increasing adiposity.
      Conclusion: Supplementing body fat percentage with five-point BCS appears to
      increase the likelihood of validating overweight status in small-medium sized dog
      breeds by detecting changes in plasma metabolite levels, especially lipids,
      induced as a result of increasing adiposity.

PMID- 30101085
TI  - cDNA cloning and mRNA expression of cat and dog Cdkal1.
AB  - The cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1
      (CDKAL1) gene encodes methylthiotransferase, and the gene contains risk variants
      for type 2 diabetes in humans. In this study, we performed complementary DNA
      cloning for Cdkal1 in the cat and dog and characterized the tissue expression
      profiles of its messenger RNA. Cat and dog Cdkal1 complementary DNA encoded 576
      and 578 amino acids, showing very high sequence homology to mammalian CDKAL1
      (>88.4%). Real-time polymerase chain reaction analyses revealed that Cdkal1
      messenger RNA is highly expressed in smooth muscle and that tissue distribution
      of Cdkal1 is similar in cats and dogs. Genotyping analysis of single-nucleotide
      polymorphism for cat Cdkal1 revealed that obese cats had different tendencies
      from normal cats. These findings suggest that the cat and dog Cdkal1 gene is
      highly conserved among mammals and that cat Cdkal1 may be a candidate marker for
      genetic diagnosis of obesity.

PMID- 30101087
TI  - Alterations with age in peripheral blood lymphocyte subpopulations and cytokine
      synthesis in beagles.
AB  - Purpose: The immune system is considered to be affected by aging, which is linked
      to various immune pathogeneses. The purpose of this study was to determine age
      associated changes in immune function of healthy dogs (beagles), specifically
      those of naive and memory T lymphocytes, based on cytokine synthesis. Patients
      and methods: Blood samples were obtained from 44 healthy beagles that were
      divided into three age-groups: young (<4 years), middle-aged (4-8 years), and
      older dogs (>8 years). Subpopulations of T lymphocytes were determined by flow
      cytometry. Transcriptional (mRNA) levels of cytokines were determined for primary
      cultured leukocytes using quantitative real-time polymerase chain reaction.
      Results: There were negative correlations between dogs' ages and the number of
      peripheral blood mononuclear cells, T cells, and B cells. In particular, the
      number of naive CD4+ CD45RA+ T cells and CD8+ CD45RA+ T cells significantly
      decreased with age. The mRNA levels for interleukin (IL)-2, IL-2Ralpha, and
      interferon-gamma were significantly higher in young or middle-aged dogs (P <
      0.05), whereas IL-4 mRNA expression was not significantly different over the
      different age-groups. IL-2Rgamma mRNA expression tended to decrease with age.
      Conclusion: Decreases of naive CD4+ and naive CD8+ T cells may be related to age
      related immunosenescence in dogs. With regard to cytokine production, leukocyte
      IL-4 and IL-10 mRNA levels did not change with age, whereas IL-2, IL-2Ralpha, and
      IL-2Rgamma mRNA levels decreased with age. These altered cytokine mRNA expression
      patterns may contribute to decreased naive T-cell function(s) with aging.

PMID- 30101088
TI  - An update on the treatment of canine atopic dermatitis.
AB  - Remarkable progress has been made in recent years concerning our understanding of
      the pathogenesis of canine atopic dermatitis (AD). As our understanding improves,
      the therapeutic approach evolves. Of utmost importance is the documentation of
      skin barrier impairment in canine AD: ceramides deficiency leads to increased
      permeability and increased allergen penetration and sensitization. It is
      currently unknown whether this dysfunction is primary and genetically inherited
      or secondary to inflammation but it is accepted that skin barrier deficiency
      plays an important role in either starting or minimally exacerbating canine AD.
      Thus, the therapeutic approach has changed from focusing on the control of the
      inflammation to a combined approach that includes therapies aimed at skin barrier
      repair. The issue of skin barrier repair has been addressed both with oral
      administration of essential fatty acids and the topical application of products
      containing a combination of ceramides and fatty acids. These strategies are most
      helpful as adjunctive treatments and would be best used in young patients that
      have not developed chronic skin changes. Importantly, treatment for canine AD is
      multimodal and tailored to the individual patient, the age, and the duration of
      the disease. Client education plays an important role in explaining the
      importance of a long-term approach to minimize flare-ups and, in this context,
      topical therapy to correct skin barrier can be of great benefit. This is an area
      still in infancy and much work is needed to identify the best formulation. In
      human medicine, long-term use of moisturizers can have a profound effect on skin
      barrier and gene expression of proteins involved in skin barrier. This effect is
      variable depending on the formulation used. It is reasonable to speculate that
      the same may be true in dogs; thus, it is very important to identify the correct
      ingredients and formulation to use.

PMID- 30101089
TI  - Mesenteric cryptococcal granuloma in a dog caused by Cryptococcus neoformans var.
      grubii.
AB  - Although cryptococcosis is usually associated with respiratory and neurologic
      signs in domestic species (such as sneeze, cough, nasal discharge, seizures,
      ataxia), clinical manifestations of the disease may be more subtle and
      nonspecific. A 3-year-old male castrated Boxer dog presented with a history of
      chronic vomiting, diarrhea, weight loss, and lethargy. At no time had respiratory
      or neurologic signs been noted by the owners or the primary care veterinarian.
      Palpation of an abdominal mass revealed an atypical lesion location: a large (16
      * 9 * 7 cm) mass at the root of the mesentery. Diagnosis was achieved through
      cytology of this mass and a positive serologic Cryptococcus capsular antigen
      titer; polymerase chain reaction was utilized for speciation of the abdominal
      isolate as Cryptococcus neoformans variety grubii. The animal was euthanized due
      to poor prognosis. After necropsy and histopathologic analysis, the mesenteric
      mass and associated lymph nodes were identified as large fungal granulomas. This
      is a rare manifestation of cryptococcosis, involving several visceral organs,
      with no remaining evidence of the route of entry of the organism. As prompt
      diagnosis of mycotic illness is paramount to successful management, this case
      indicates that cryptococcal infection should be considered as a differential
      diagnosis in dogs with gastrointestinal signs and lymphadenopathy. The protean
      nature of cryptococcosis is discussed within the context of a brief review of
      emerging and unresolved issues in pathogenesis.

PMID- 30101090
TI  - Effects of endotoxemia on the pharmacodynamics and pharmacokinetics of ketamine
      and xylazine anesthesia in Sprague-Dawley rats.
AB  - Purpose: To evaluate the effects of endotoxemia on the pharmacokinetics and
      pharmacodynamics of ketamine and xylazine anesthesia in Sprague-Dawley rats.
      Methods: Sprague-Dawley rats received ketamine (80 mg/kg) and xylazine (5 mg/kg)
      intramuscularly following the intraperitoneal administration of different
      lipopolysaccharide concentrations (1, 10, and 100 ug/kg) to simulate different
      levels of endotoxemia. Results were compared to control animals receiving saline
      intraperitoneally. During anesthesia, a toe pinch was performed to evaluate
      anesthesia duration, and selected physiological parameters (heart and respiratory
      rates, oxygen saturation, and rectal temperature) were taken. Blood samples were
      also taken during anesthesia at selected time points for the analysis of
      plasmatic ketamine and xylazine concentrations by liquid chromatography-mass
      spectrometry. Blood samples were taken 1 week prior to and 24 hours following
      anesthesia for blood biochemistry. Results: Anesthesia duration significantly
      increased for moderate (10 ug/kg) and high (100 ug/kg) lipopolysaccharide groups.
      Liver histopathology showed minor to moderate necrosis in all lipopolysaccharide
      groups in some animals. The most important physiological change that occurred was
      a decrease in oxygen saturation, and for blood biochemistry a decrease in serum
      albumin. Ketamine pharmacokinetics were not affected except for the moderate (10
      ug/kg) lipopolysaccharide group where a decrease in the area under the plasma
      concentration-time curve from time zero to the last measurable concentration, a
      decrease in half-life, and an increase in the clearance were observed. For
      xylazine, the area under the plasma concentration-time curve increased and the
      clearance decreased in the moderate (10 ug/kg) and high (100 ug/kg)
      lipopolysaccharide groups. Conclusion: During ketamine-xylazine anesthesia,
      endotoxemia may alter xylazine pharmacokinetics and selected biochemical and
      physiological parameters, suggesting that anesthetic drug dosages could be
      modified for a more rapid recovery.

PMID- 30101091
TI  - Feasibility of flotation concentration of fungal spores as a method to identify
      toxigenic mushrooms.
AB  - Purpose: Mushroom poisoning is a recurring and challenging problem in veterinary
      medicine. Diagnosis of mushroom exposure in animals is hampered by the lack of
      rapid diagnostic tests. Our study evaluated the feasibility of using flotation
      concentration and microscopic evaluation of spores for mushroom identification.
      Evaluation of this method in living animals exposed to toxigenic mushrooms is
      limited by ethical constraints; therefore, we relied upon the use of an in vitro
      model that mimics the oral and gastric phases of digestion. Methods: In our
      study, mycologist-identified toxigenic (poisonous) and nontoxigenic fresh
      mushrooms were collected in North Carolina, USA. In phase 1, quantitative spore
      recovery rates were determined following magnesium sulfate, modified Sheather's
      sugar solution, and zinc sulfate flotation (n=16 fungal species). In phase 2,
      mushrooms (n=40 fungal species) were macerated and digested for up to 2 hours in
      a salivary and gastric juice simulant. The partially digested material was acid
      neutralized, filtered, and spores concentrated using zinc sulfate flotation
      followed by microscopic evaluation of spore morphology. Results: Mean spore
      recovery rates for the three flotation fluids ranged from 32.5% to 41.0%
      (P=0.82). Mean (+/- standard error of the mean) Amanita spp. spore recovery rates
      were 38.1%+/-3.4%, 36.9%+/-8.6%, and 74.5%+/-1.6% (P=0.0012) for the magnesium
      sulfate, Sheather's sugar, and zinc sulfate solutions, respectively. Zinc sulfate
      flotation following in vitro acid digestion (phase 2) yielded spore numbers
      adequate for microscopic visualization in 97.5% of trials. The most common spore
      shapes observed were globose, spiked, elliptical, smooth and reticulate.
      Conclusion: Flotation can concentrate mushroom spores; however, false negative
      results can occur. Spore morphology could not be used to differentiate species of
      mushroom-forming fungi since the spore shape and surface characteristics seen in
      the present study were often observed with multiple species of mushroom-forming
      fungi.

PMID- 30101092
TI  - Dens agenesis and cervical vertebral malformation in a Labrador Retriever puppy.
AB  - Cervical vertebral malformations can cause acute or progressive pain, paralysis,
      and potentially death. Herein we present a case report of dens agenesis; cervical
      vertebral malformations of C1, C2, C6, and C7; subluxation of C1 and C2 and C4
      and C5; and associated degenerative myelopathy in a 5-month-old female Labrador
      Retriever puppy. We additionally review current knowledge regarding pathogenesis
      and treatment.

PMID- 30101093
TI  - Jet set pets: examining the zoonosis risk in animal import and travel across the
      European Union.
AB  - Ownership of companion animals or pets is popular throughout the world.
      Unfortunately, such animals are susceptible to and potential reservoirs of
      zoonotic pathogens. Close proximity to and contact with pets can lead to human
      infections. The distribution of zoonotic diseases associated with companion
      animals such as dogs and cats is not uniform around the world, and moving animals
      between regions, countries, and continents carries with it the risk of relocating
      the pathogens they might harbor. Critical among these zoonotic diseases are
      rabies, echinococcosis, and leishmania. In addition, the protozoan parasites,
      Toxoplasma gondii and Giardia duodenalis, are also significant agents for human
      disease of pet origin. Considerable effort is applied to controlling movements of
      companion animals, particularly dogs, into the European Union. However, free
      movement of people and their pets within the European Union is a risk factor for
      the translocation of diseases and their vectors. This review considers the
      current distribution of some of these diseases, the risks associated with pet
      travel, and the controls implemented within Europe to prevent the free movement
      of zoonotic pathogens.

PMID- 30101095
TI  - The management of equine acute laminitis.
AB  - Laminitis is an extremely painful condition resulting in damage to the soft
      tissues anchoring the third phalanx to the hoof, which can result in life
      threatening debilitation. Specific therapy is not available. The most important
      principles of therapy include aggressive nutritional and medical management of
      primary disease processes, cryotherapy, anti-inflammatory therapy, pain
      management, and biomechanical support. This review focuses on the principles of
      evidenced-based therapies.

PMID- 30101094
TI  - The role of badgers in the epidemiology of Mycobacterium bovis infection
      (tuberculosis) in cattle in the United Kingdom and the Republic of Ireland:
      current perspectives on control strategies.
AB  - Bovine tuberculosis (TB), caused by infection with Mycobacterium bovis, is a
      persistent problem in cattle herds in Ireland and the United Kingdom, resulting
      in hardship for affected farmers and substantial ongoing national exchequer
      expenditure. There is irrefutable scientific evidence that badgers are a
      reservoir of M. bovis infection and are implicated in the transmission of
      infection to cattle. A range of options for the control of TB in badgers is
      currently available or under development including culling of badgers,
      vaccination of badgers and cattle, and improved biosecurity to limit contact
      between the two species. It is unlikely that the eradication of TB from cattle
      will be achieved without the reservoir of M. bovis infection in badgers being
      controlled. The chances of success will, however, improve with greater knowledge
      of the disease in both species and an understanding of the epidemiological
      drivers of the transmission of infection between badgers and cattle.

PMID- 30101097
TI  - Plasma concentrations of fenbendazole (FBZ) and oxfendazole in alpacas (Lama
      pacos) after single intravenous and oral dosing of FBZ.
AB  - The objective of this study was to determine plasma pharmacokinetics and
      bioavailability of fenbendazole (FBZ) and oxfendazole (OFZ) after intravenous
      (iv) and oral administrations of FBZ (5 mg/kg) to alpacas. Plasma concentrations
      of FBZ and OFZ after administration of FBZ iv and orally (5 mg/kg) were
      determined by high-performance liquid chromatography with ultraviolet detection.
      Total clearance (CL) of FBZ was 16.5+/-4 mL/kg/min (range: 4-31 mL/kg/min), and
      steady-state volume of distribution (Vdss) was 3.3+/-1 L/kg (range: 1.7-7.4
      L/kg). The terminal phase half-life of FBZ after iv administration was 5.9+/-3.8
      hours (range: 0.8-20 hours). After oral administration, the FBZ terminal phase
      half-life was 23+/-5 hours (range: 9-37 hours) and the systemic bioavailability
      of FBZ was 16%+/-6% (range: 1%-41%). Peak FBZ concentrations after oral
      administration were 0.13+/-0.05 ug/mL (range: 0.05-0.28 ug/mL) at 10 hours
      (range: 8-12 hours). Peak plasma OFZ concentrations after oral dosing with FBZ (5
      mg/kg) were 0.14+/-0.05 ug/mL (0.05-0.3 ug/mL) at 24+/-7 hours (range: 12-48
      hours). FBZ clearance is lower in comparison to that of other species. Systemic
      availability of FBZ after oral administration is low after oral dosing.
      Metabolites of FBZ produced by alpacas are similar to those observed in other
      species.

PMID- 30101098
TI  - The diagnosis and management of atrial fibrillation in the horse.
AB  - Atrial fibrillation is the most common performance-limiting arrhythmia in the
      horse. Detailed cardiovascular evaluation will help guide prognosis and
      treatment. Many affected horses have lone atrial fibrillation (no predisposing
      cardiac abnormalities). These horses have a good prognosis for return to
      performance if sinus rhythm can be restored. The main therapeutic option
      continues to be quinidine, which has been used for over 60 years. Transvenous
      electrical cardioversion has proven to be a successful alternative. Other
      therapeutic options are being explored, but are currently limited.

PMID- 30101099
TI  - Frequency of the MDR1 mutant allele associated with multidrug sensitivity in dogs
      from Brazil.
AB  - To date, a 4-bp deletion in the MDR1 gene has been detected in more than ten dog
      breeds, as well as in mixed breed dogs, in several countries, however information
      regarding this mutation in dogs from Brazil is lacking. For this reason, 103
      Collies, 77 Border Collies, 76 Shetland Sheepdogs, 20 Old English Sheepdogs, 55
      German Shepherds, 16 Australian Shepherds, and 53 Whippets from Brazil were
      screened for the presence of the mutation. The heterozygous mutated genotype,
      MDR1 (+/-), frequency found for Collies, Australian Shepherd, and Shetland
      Sheepdog was 50.5% (95% CI =41.1%-59.9%), 31.3% (95% CI =8.6%-53.2%), and 15.8%
      (95% CI =7.7%-23.9%), respectively. Homozygous mutated genotype, MDR1 (-/-), was
      detected only in Collies 35.9%. The MDR1 allele mutant frequency found for
      Collies, Australian Shepherd, and Shetland Sheepdog was 61.2% (95% CI =54.8%
      67.5%), 15.6% (95% CI =3.1%-28.2%), and 7.9% (95% CI =3.7%-12.1%), respectively.
      Additionally, even free of the mutant allele, the maximum mutant prevalence (MMP)
      in that population, with 95% CI, was 3.8%, 5.2%, 5.4%, and 13.8% for Border
      Collies, German Shepherds, Whippets, and Old English Sheepdogs, respectively. In
      this way, this information is important, not only for MDR1 genotype-based
      breeding programs and international exchange of breeding animals of predisposed
      breeds, but also for modification of drug therapy for breeds at risk.

PMID- 30101096
TI  - Canine and feline obesity: a review of pathophysiology, epidemiology, and
      clinical management.
AB  - Canine and feline obesity rates have reached pandemic proportions and are similar
      to those in humans, with approximately 30%-40% of dogs and cats being overweight
      to obese. Obesity has been associated with other health problems, including
      osteoarthritis, renal disease, skin disease, insulin resistance, and neoplasia in
      dogs, while in cats obesity is associated with dermatological issues, diabetes
      mellitus, neoplasia, and urolithiasis. The health issues appear to be slightly
      different across the two species, which may be due to some inherent differences
      in the hormonal milieu involved in obesity that differs between the dog and the
      cat. In this review, we discuss the complicated nature of the pathogenesis of
      obesity, the hormonal stimulus for orexigenic and anorexigenic behavior, adipose
      tissue as an endocrine organ, and most importantly, clinical management of the
      number one disease in canine and feline medicine.

PMID- 30101100
TI  - Update on insulin treatment for dogs and cats: insulin dosing pens and more.
AB  - Insulin therapy is still the primary therapy for all diabetic dogs and cats.
      Several insulin options are available for each species, including veterinary
      registered products and human insulin preparations. The insulin chosen depends on
      the individual patient's requirements. Intermediate-acting insulin is usually the
      first choice for dogs, and longer-acting insulin is the first choice for cats.
      Once the insulin type is chosen, the best method of insulin administration should
      be considered. Traditionally, insulin vials and syringes have been used, but
      insulin pen devices have recently entered the veterinary market. Pens have
      different handling requirements when compared with standard insulin vials
      including: storage out of the refrigerator for some insulin preparations once pen
      cartridges are in use; priming of the pen to ensure a full dose of insulin is
      administered; and holding the pen device in place for several seconds during the
      injection. Many different types of pen devices are available, with features such
      as half-unit dosing, large dials for visually impaired people, and memory that
      can display the last time and dose of insulin administered. Insulin pens come in
      both reusable and disposable options. Pens have several benefits over syringes,
      including improved dose accuracy, especially for low insulin doses.

PMID- 30101101
TI  - Puppy parties and beyond: the role of early age socialization practices on adult
      dog behavior.
AB  - The most common role of a domestic dog in the developed world currently is that
      of companion. Puppy socialization practices play a large role in the development
      of well-adjusted adult dogs that display few undesirable behaviors, and which can
      establish a positive, lifelong relationship with their owner. Age-appropriate
      socialization practices should begin within a few days of birth, and should
      extend well into adulthood. These practices should aim to provide exposure to
      many of the types of experiences, people, and objects that the dog is likely to
      encounter over the course of its life, in a controlled and pleasant way. Dogs
      that are appropriately socialized as puppies are less likely to exhibit
      behavioral problems as adults, including aggression and fearfulness. They are
      more likely to engage in positive social behaviors with humans, and can learn how
      to play games with humans better than dogs without proper socialization. However,
      the evidence in support of puppy socialization classes is less clear. There is
      some evidence that puppy classes positively impact adult behavior, but other
      studies show no clear benefit. Since socialization should begin early in a
      puppy's life, it is the responsibility of the breeder and the owner. Breeders can
      ensure that puppies are exposed to age-appropriate experiences while in the
      litter, and owners must ensure that the dog continues to have varied experiences
      throughout its life. Veterinarians are also an important part of this process,
      and are heavily relied upon by owners to provide information about health and
      behavior. Since veterinarians often see puppies during vaccinations, owners can
      be educated about proper socialization practices at those visits. Future research
      should aim to determine the minimum amounts of socialization required for a
      puppy, and whether there is a maximum amount, beyond which there is no benefit,
      or even a disadvantage.

PMID- 30101103
TI  - Surgical treatment of an umbilical hernia in a free-ranging sub-adult African
      elephant in Samburu National Reserve, Kenya.
AB  - A 10-year-old male African elephant (Loxodonta africana) at Samburu National
      Reserve in Northern Kenya, weighing approximately 1,600 kg, presented with an
      umbilical hernia in October 2013. Umbilical herniorrhaphy was carried out under
      field conditions. Anesthesia was induced and maintained using etorphine
      hydrochloride for 3 hours during the surgery. This case report details both the
      surgical and anesthetic procedure carried out to correct the hernia, and the
      eventual successful recovery of the elephant from anesthesia. However, the
      elephant died weeks after the surgery and a postmortem could not reveal the cause
      of death because predators had scavenged the carcass. The challenges of the
      surgical procedure and outcome including possible causes of death are highlighted
      in this report.

PMID- 30101102
TI  - The etiology of digital dermatitis in ruminants: recent perspectives.
AB  - Digital dermatitis (DD) is a multifactorial polymicrobial infectious disease
      originally described in dairy cattle, but is increasingly recognized in beef
      cattle, sheep, and more recently, elk and goats. Clinical bovine lesions
      typically appear on the plantar surface of the hind foot from the interdigital
      space and heel bulb to the accessory digits, with a predilection for skin-horn
      junctions. Lesions present as a painful ulcerative acute or chronic inflammatory
      process with differing degrees of severity. This variability reflects disease
      progression and results in a number of different clinical descriptions with
      overlapping pathologies that ultimately have a related bacterial etiology. The
      goal of this review article is to provide a concise overview of our current
      understanding on digital dermatitis disease to facilitate clinical recognition,
      our current understanding on the causative agents, and recent advances in our
      understanding of disease transmission.

PMID- 30101104
TI  - Current perspectives on the optimal age to spay/castrate dogs and cats.
AB  - Spaying and castrating of dogs and cats has been considered for decades to be a
      routine standard of practice in veterinary medicine in the US for the prevention
      of numerous undesirable behaviors, medical conditions, and diseases.
      Additionally, the procedures have been promoted as a method of curbing the severe
      pet-overpopulation problem in the US. Recently, however, this routine practice
      has come under scrutiny and become a very controversial topic. The general wisdom
      and safety of the procedures have been questioned by those who are concerned that
      the procedures may have some unintended consequences that are only recently being
      recognized. The purpose of this paper is to critically examine the scientific
      literature regarding elective spay/castration procedures and present both risks
      and benefits of elective gonadectomy. After the literature is examined, it
      becomes clear that there may not be a single absolute optimal age to spay or
      castrate all dogs and cats, but that the optimal age may be dependent upon
      several factors, including species, breed, body size, and breed-specific
      diseases, among others. Determining the optimal age to perform elective
      gonadectomy is much clearer in cats, and the literature demonstrates that the
      procedures can typically be safely performed at any age after 6-8 weeks of age.
      The optimal age to spay or castrate dogs of certain breeds (rottweiler, golden
      retriever, Labrador retriever, and vizsla) is becoming less clear as studies are
      being conducted as to the health benefits and risks in those breeds. This review
      will examine these controversies and make recommendations as to the optimal age
      to spay/castrate dogs based upon the scientific literature.

PMID- 30101105
TI  - Diagnosis, prevention, and management of canine hip dysplasia: a review.
AB  - Canine hip dysplasia (CHD) is a polygenic and multifactorial developmental
      disorder characterized by coxofemoral (hip) joint laxity, degeneration, and
      osteoarthritis (OA). Current diagnostic techniques are largely subjective
      measures of joint conformation performed at different stages of development.
      Recently, measures on three-dimensional images generated from computed tomography
      scans predicted the development of OA associated with CHD. Continued refinement
      of similar imaging methods may improve diagnostic imaging techniques to identify
      dogs predisposed to degenerative hip joint changes. By current consensus, joint
      changes consistent with CHD are influenced by genetic predisposition as well as
      environmental and biomechanical factors; however, despite decades of work, the
      relative contributions of each to the development and extent of CHD signs remain
      elusive. Similarly, despite considerable effort to decipher the genetic
      underpinnings of CHD for selective breeding programs, relevant genetic loci
      remain equivocal. As such, prevention of CHD within domestic canine populations
      is marginally successful. Conservative management is often employed to manage
      signs of CHD, with lifelong maintenance of body mass as one of the most promising
      methods. Surgical intervention is often employed to prevent joint changes or
      restore joint function, but there are no gold standards for either goal. To date,
      all CHD phenotypes are considered as a single entity in spite of recognized
      differences in expression and response to environmental conditions and treatment.
      Identification of distinct CHD phenotypes and targeting evidence-based
      conservative and invasive treatments for each may significantly advance
      prevention and management of a prevalent, debilitating condition in canine
      companions.

PMID- 30101106
TI  - Emerging insights into the genetic basis of canine hip dysplasia.
AB  - Canine hip dysplasia (CHD) is the most common inherited polygenic orthopedic
      trait in dogs with the phenotype influenced also by environmental factors. This
      trait was described in the dog in 1935 and leads to a debilitating secondary hip
      osteoarthritis. The diagnosis is confirmed radiographically by evaluating signs
      of degenerative joint disease, incongruence, and/or passive hip joint laxity.
      There is no ideal medical or surgical treatment so prevention based on controlled
      breeding is the optimal approach. The definitive CHD diagnosis based on
      radiographic examination involves the exposure to ionizing radiation under
      general anesthesia or heavy sedation but the image does not reveal the underlying
      genetic quality of the dog. Phenotypic expression of CHD is modified by
      environmental factors and dogs with a normal phenotype can be carriers of some
      mutations and transmit these genes to their offspring. Programs based on
      selection of dogs with better individual phenotypes for breeding are effective
      when strictly applied but remain inferior to the selection of dogs based on
      estimation of breeding values. Molecular studies for dissecting the genetic basis
      of CHD are ongoing, but progress has been slow. In the future, the recommended
      method to improve hip quality in controlled breeding schemes, which will allow
      higher selection pressure, would be based on the estimation of the genomic
      breeding value. Since 2012, a commercial DNA test has been available for Labrador
      Retrievers using a blood sample and provides a probability for development of CHD
      but we await evidence that this test reduces the incidence or severity of CHD.

PMID- 30101107
TI  - Assessment of quality of life in veterinary practice: developing tools for
      companion animal carers and veterinarians.
AB  - Quality-of-life assessments aim to provide an all-encompassing evaluation of
      animal welfare. In comparison to more limited, disease-focused welfare
      assessments, they have the potential to better identify welfare deficiencies,
      allowing veterinarians to target improvement strategies for greater benefit.
      Individuals or populations of companion animals may be assessed and carers and/or
      veterinarians may contribute to the assessment. Quality-of-life assessments are
      widely used within the human health care setting, and although the number of
      veterinary assessment tools is substantially fewer, these tools cover a range of
      methodologies. Further research to validate existing tools and develop new ones
      is recommended. Guidance for implementing and evaluating the usefulness of
      quality-of-life assessment tools within companion animal veterinary clinics is
      presented.

PMID- 30101108
TI  - Reversal of echocardiographic right-sided heart pathology in a dog with severe
      pulmonary hypertension: a case report.
AB  - Pathologic right-sided heart changes are a common echocardiographic finding in
      patients with pulmonary hypertension (PH). Canines with PH may have right heart
      pathology documented via echocardiographic color Doppler interrogation including
      tricuspid valve regurgitation, pulmonic valve insufficiency, elevated pulmonary
      arterial systolic pressure, elevated pulmonary arterial diastolic pressure, and
      alterations in ejection profiles. Two-dimensional echocardiographic findings may
      include right ventricular hypertrophy, interventricular septal flattening,
      paradoxical interventricular septal motion, pulmonary artery dilation, and
      potentially abnormal left heart dimensions. In veterinary medicine, much
      confidence is given to the measurement of pulmonary arterial systolic pressure
      estimated from tricuspid valve regurgitation to grade the severity of PH and
      monitor its improvement with little emphasis placed on the integration of two
      dimensional echocardiographic right and left heart pathology in conjunction with
      Doppler findings. To the authors' knowledge, marked improvement and/or resolution
      of echocardiographic-documented right heart pathology have not been previously
      reported in the veterinary literature. This case report documents profound
      echocardiographic improvement of right-sided heart disease in a dog with severe
      PH.

PMID- 30101109
TI  - Strategies for the management and prevention of conformation-related respiratory
      disorders in brachycephalic dogs.
AB  - Brachycephalic (short-muzzled) dogs are increasingly popular pets worldwide, with
      marked increases in registrations of breeds such as the Pug and French Bulldog
      over the past decade in the UK. Despite their popularity, many brachycephalic
      breeds are affected by an early-onset, lifelong respiratory disorder,
      brachycephalic obstructive airway syndrome (BOAS). This disorder arises due to a
      mismatch in the proportions of the skull and the soft tissues held within the
      nose and pharynx, resulting in obstruction of the airway during respiration.
      Increased airway resistance encourages secondary changes such as eversion of the
      laryngeal saccules and collapse of the larynx. Clinical signs of BOAS are often
      early onset and chronic, including dyspnea, exercise intolerance, heat
      intolerance, and abnormal and increased respiratory noise. Episodes of severe
      dyspnea can also occur, leading to cyanosis, syncope, and death. BOAS may have a
      severe impact upon the welfare of affected dogs, compromising their ability to
      exercise, play, eat, and sleep. Although a well-described condition, with
      surgical treatments for the palliation of this disorder published since the
      1920s, many dogs still experience airway restrictions postsurgically and a
      compromised quality of life. In addition, the prevalence of this disorder does
      not appear to have substantially reduced in this time, and may have increased.
      Ultimately, strategies to improve the breeding of these dogs to prevent BOAS are
      required to improve brachycephalic health and welfare. Recent studies have
      revealed conformational risk factors associated with BOAS, such as short muzzles
      and thick necks, which should be discouraged to avoid perpetuating this serious
      disorder. Positive changes to brachycephalic health may be impeded by a
      perception of BOAS being "normal for the breed". This perception must be avoided
      by owners, breeders, and vets alike to prevent undertreatment of individuals and
      the perpetuation of this serious disorder to future generations of dogs.

PMID- 30101110
TI  - Fetal mummification in the major domestic species: current perspectives on causes
      and management.
AB  - Fetal mummification is an uncommon condition in most domestic species. While most
      often seen in multiparous and polytocous species like swine, it is also observed
      in monotocous species when the fetus is retained for a long time. The low
      prevalence of the condition may help explain the scarcity of information in the
      literature. To further complicate the study of this phenomenon, the physiological
      mechanisms that maintain pregnancy vary between species, implying different
      pathways for the condition. The exact outcome of early fetal mortality is
      unpredictable, and is influenced by several factors, including the cause of fetal
      mortality, differences in pregnancy between species, stage of gestation at fetal
      death, and number of fetuses. Based on our current knowledge of natural fetal
      mummification events, there are a number of prerequisites for the process of
      fetal mummification to occur. Examining the circumstances associated with fetal
      mummification can help scientists better understand the etiology and clinical
      situation in different species. The objective of this article is to review fetal
      mummification in the major domestic species: cattle, goats, sheep, horses, swine,
      dogs, and cats. This paper discusses the clinical situation, the most common and
      important etiologies, and the treatment approaches for restoring future pregnancy
      in the female, and where applicable, herd fertility.

PMID- 30101111
TI  - Recent advances in canine leptospirosis: focus on vaccine development.
AB  - Leptospirosis is a global infection of humans and animals caused by pathogenic
      Leptospira spp. Leptospirosis is a major zoonosis, with infection acquired from
      wild and domestic animals. It is also a significant cause of morbidity,
      mortality, and economic loss in production and companion animals. Leptospirosis
      in dogs is prevalent worldwide and as well as a cause of canine disease, it
      presents a zoonotic risk to human contacts. Canine leptospirosis does not differ
      greatly from the syndromes seen in other animal species, with hepatic, renal, and
      pulmonary involvement being the main manifestations. While the pathogenesis of
      disease is well documented at the whole animal level, the cellular and molecular
      basis remains obscure. Killed, whole-cell bacterin vaccines are licensed
      worldwide and have not changed greatly over the past several decades. Vaccine
      induced immunity is restricted to serologically related serovars and is generally
      short-lived, necessitating annual revaccination. The appearance of new serovars
      as causes of canine leptospirosis requires constant epidemiological surveillance
      and tailoring of vaccines to cover emerging serovars. At the present time, there
      is no realistic prospect of alternative, non-bacterin vaccines in the foreseeable
      future.

PMID- 30101112
TI  - Schmallenberg virus infection of ruminants: challenges and opportunities for
      veterinarians.
AB  - In 2011, European ruminant flocks were infected by Schmallenberg virus (SBV)
      leading to transient disease in adult cattle but abortions and congenital
      deformities in calves, lambs, and goat kids. SBV belonging to the Simbu serogroup
      (family Bunyaviridae and genus Orthobunyavirus) was first discovered in the same
      region where bluetongue virus serotype 8 (BTV-8) emerged 5 years before. Both
      viruses are transmitted by biting midges (Culicoides spp.) and share several
      similarities. This paper describes the current knowledge of temporal and
      geographical spread, molecular virology, transmission and susceptible species,
      clinical signs, diagnosis, prevention and control, impact on ruminant health, and
      productivity of SBV infection in Europe, and compares SBV infection with BTV-8
      infection in ruminants.

PMID- 30101114
TI  - Equine pituitary pars intermedia dysfunction: current perspectives on diagnosis
      and management.
AB  - Equine pituitary pars intermedia dysfunction (PPID) is a neurodegenerative
      disease of the hypothalamus, resulting in the loss of dopaminergic inhibition of
      pars intermedia. An oxidative stress injury of unknown etiology has been
      suggested to initiate the neurodegeneration. While hypertrichosis (formerly known
      as hirsutism) is considered pathognomic for advanced disease, the antemortem
      diagnosis of subclinical and early disease has continued to prove difficult.
      Numerous tests have been used with varying sensitivities and specificities. The
      overnight dexamethasone suppression test, originally documented to have 100%
      sensitivity and specificity in horses with advanced disease, has proven to be
      less valuable in identifying early disease. Basal plasma adrenocorticotropin
      concentrations have improved sensitivity and specificity when sampled during the
      autumn months, and alpha-melanocyte-stimulating hormone, while not yet
      commercially available, shows promise as a sensitive and specific single sample
      test. Recent advances in our knowledge include the strong association between
      laminitis and hyperinsulinemia, both common clinical signs associated with PPID.
      The pathogenesis of hyperinsulinemia, laminitis, and their association with this
      disease is a focus of current research. The dopamine agonist pergolide mesylate
      is still the mainstay of medical management, with studies on oral
      bioavailability, pharmacokinetics, and long-term survival rates now published.

PMID- 30101113
TI  - Perspectives on the treatment of claw lesions in cattle.
AB  - Lameness is a leading cause of welfare and culling issues in cattle, with claw
      lesions accounting for the majority of these issues. Although the treatment of
      claw lesions in cattle is a daily activity for hoof trimmers, veterinarians, and
      livestock producers, there is surprisingly little information in the peer
      reviewed literature on which to base strong evidence-based conclusions. As a
      consequence, many treatment modalities used are empirical and, in some cases, may
      be counterproductive to rapid lesion healing. Furthermore, many of these
      empirical treatment modalities fail to fully consider the underlying pathogenesis
      of the disease process and the implications that it has on lesion healing. For
      example, sole ulcers are largely a consequence of metabolic disorders and
      mechanical overloading. Therapeutic interventions that fail to address the weight
      bearing issues are unlikely to be successful. Likewise, white line disease is
      believed to be predisposed by rumen acidosis and laminitis, and interventions
      need to include in them appropriate measures to prevent further cases through
      nutritional management. The goal of this review paper is to review the
      pathogenesis of claw lesions in the context of the published literature and allow
      the reader to arrive at rational treatment interventions based on the best
      available information. The use of an orthopedic block applied to the healthy claw
      of a lame foot, judicious use of bandage or wrap, careful selection of parenteral
      or topical therapy, and a treatment protocol to manage pain and promote recovery
      are key components of responsible management of lameness disorders in cattle.

PMID- 30101115
TI  - Seizures in horses: diagnosis and classification.
AB  - Seizures are a diverse and very common set of chronic neurologic disorders in
      humans and dogs but are less common in horses. Seizures refer to a specific
      clinical event (described as sudden and severe) regardless of the etiology, which
      includes both intracranial and extracranial causes. Therefore, after briefly
      reviewing some definitions, this article aims to describe the use of a
      standardized classification, which could facilitate a logical approach for the
      clinician to establish a diagnosis, as well as to use a consistent mode of
      communication. For instance, seizures can be classified by type (ie, focal vs
      generalized) or etiology (ie, reactive, symptomatic, cryptogenic, idiopathic). In
      particular, epilepsy, a brain disorder characterized by recurrent seizures can be
      classified as primary (ie, genetic origin) or secondary (ie, acquired). This
      review further discusses the limitations associated with the clinical workup of
      horses with seizures. This is germane to the fact that the identification of the
      underlying cause remains challenging due to the technical limitations of imaging
      the equine adult brain. Indeed, as in man and dogs, epilepsies of unknown cause
      (ie, cryptogenic) account for the majority of all epilepsies. Therefore, although
      electroencephalography and advanced brain imaging techniques (eg, computed
      tomography and magnetic resonance imaging) are becoming increasingly available,
      information obtained from the history, physical, and neurologic examinations and
      progression of clinical signs and response to treatment remain essential in the
      workup of horses with seizures.

PMID- 30101117
TI  - Growth curves and their implications in hand-fed Monk parrots (Myiopsitta
      monachus).
AB  - Monk parrots (Myiopsitta monachus) were hand-fed over two chick seasons spanning
      of 2010 to 2011. Information from the growth curve of chicks hand-fed in 2010 was
      used to develop a feeding protocol for the 2011 season (Protocol-2011). This
      protocol addressed the problems of delayed followed by excessive growth
      experienced by parrots hand fed in 2010. Monk parrots that were hand-fed in 2011
      following the new protocol experienced delayed growth after 20 days of age.
      However, some Monk parrots were fed in excess of Protocol-2011 and did not
      experience a major delay in growth. The energy requirement equations used to
      construct Protocol-2011 were low when compared to adult Monk parrot maintenance
      energy requirements. The data suggest that growing birds do not require
      approximately twice their adult maintenance energy requirements, as is the case
      for growing dogs. Additionally, there appear to be fluctuations in energy needs
      as Monk parrots grow. A major increase in energy needs occurred between days 18
      and 23 posthatching, which corresponds to feather development and growth in Monk
      parrot chicks. Thus, multiple equations estimating energy requirements, rather
      than just one equation, are likely needed from hatching to fledging in order to
      ensure adequate energy is provided to chicks. More research on the energy
      requirements of growing Monk parrots, especially around the time of fledging and
      weaning, is needed to improve hand-fed methods and potentially the adult health
      of hand-fed birds.

PMID- 30101116
TI  - Recent advancements in the hormonal stimulation of ovulation in swine.
AB  - Induction of ovulation for controlled breeding is available for use around the
      world, and conditions for practical application appear promising. Many of the
      hormones available, such as human chorionic gonadotropin (hCG), gonadotropin
      releasing hormone (GnRH) and its analogs, as well as porcine luteinizing hormone
      (pLH), have been shown to be effective for advancing or synchronizing ovulation
      in gilts and weaned sows. Each of the hormones has unique attributes with respect
      to the physiology of its actions, how it is administered, its efficacy, and
      approval for use. The timing for induction of ovulation during the follicle phase
      is critical as follicle maturity changes over time, and the success of the
      response is determined by the stage of follicle development. Female fertility is
      also a primary factor affecting the success of ovulation induction and fixed time
      insemination protocols. Approximately 80%-90% of female pigs will develop mature
      follicles following weaning in sows and synchronization of estrus in gilts.
      However, those gilts and sows with follicles that are less developed and mature,
      or those that develop with abnormalities, will not respond to an ovulatory surge
      of LH. To address this problem, some protocols induce follicle development in all
      females, which can improve the overall reliability of the ovulation response.
      Control of ovulation is practical for use with fixed time artificial insemination
      and should prove highly advantageous for low-dose and single-service artificial
      insemination and for use with frozen-thawed and sex-sorted sperm.

PMID- 30101118
TI  - A survey on orthopedic injuries during a marathon sled dog race.
AB  - Purpose: This prospective observational study aimed to describe and quantify
      orthopedic injuries (OI) during a marathon sled dog race that led to
      discontinuation of racing (dropped dogs [DDs]) and to suggest potential
      associations with risk factors during the event. Study design: Prospective
      observational study. Animals: A total of 989 Nordic breed endurance sled dogs
      that participated in the 2011 Iditarod Sled Dog Race. Data were collected via an
      extensive questionnaire, medical records, and speed calculations based on Global
      Positioning System equipment on each dog sled. OI risk factors and DD incidence
      were statistically analyzed on dogs and teams completing at least half the race
      distance, including Student's t-test, Pearson's chi-squared test, Poisson
      regression, and various frailty analysis models as indicated. Significance was
      set at P<0.10 for inclusion in the models with trends established at P<=0.10 and
      significance declared at P<0.05. Results: Questionnaire response was 40.3%. DD
      incidence was 38.3%, most often due to OI (50.6%). OI occurred most frequently in
      the thoracic limb (43.3%) compared with pelvic limb injuries (7.3%). Increased
      speed was associated with fewer shoulder injuries (Ratio=0.65, P=0.03). Carpal
      injuries were positively related with increased conditioning distance (defined as
      training miles; Hazard ratio =1.61, P=0.02). The risk to become a DD decreased
      with every year of increased age of the dogs (Hazard ratio =0.92, P=0.03).
      Conclusion: OI, specifically of the shoulder and carpus, are common in marathon
      sled dogs. Injury risk may be speed-related and decreases with increasing age of
      the dog. Further study of environmental, dietary, and trail conditions in sled
      dog racing orthopedic research is needed.

PMID- 30101120
TI  - Recognizing and responding to cases of suspected animal cruelty, abuse, and
      neglect: what the veterinarian needs to know.
AB  - The identification of a "battered pets" syndrome, which put the veterinary
      profession on a parallel footing with its counterparts in human medicine who
      respond to battered children, women, and elders, expanded the veterinarian's role
      as an advocate for animals' welfare to include the recognition of, response to,
      and prevention of animal abuse. Professional policies and legislation in several
      nations have been amended to define these responsibilities and delineate
      appropriate responses when animal maltreatment or other forms of family violence
      are suspected. This article reviews these changes, discusses abuse as a matter of
      animal welfare and public health, and summarizes research describing animal abuse
      as a possible indicator and predictor of interpersonal violence. Five steps that
      helped build human health care's response to child abuse, domestic violence, and
      elder abuse, and that are analogous to forces in contemporary veterinary
      practice, are described. It familiarizes practitioners with terminology used in
      animal cruelty investigations. It describes clinical presentations, client
      profiles and behaviors, and environmental conditions that may raise a
      practitioner's index of suspicion of possible animal maltreatment. It reviews
      protocols that practitioners may employ to respond compassionately and
      effectively to suspected animal abuse and enhance successful law enforcement
      investigations and prosecutions. Such responses can unite human and veterinary
      medicine in a common concern for vulnerable, victimized, and at-risk populations
      and position veterinarians as an essential part of public health approaches to
      break the cycles of violence affecting animals and human members of the family
      and community.

PMID- 30101119
TI  - Immune-mediated keratoconjunctivitis sicca in dogs: current perspectives on
      management.
AB  - Keratoconjunctivitis sicca (KCS) is a frequent canine ophthalmic disease,
      resulting from the deficiency of one or more elements in the precorneal tear
      film. There are different known causes of KCS in dogs, including congenital,
      metabolic, infectious, drug induced, neurogenic, radiation, iatrogenic,
      idiopathic, and immune mediated, though the last one is the most prevalent form
      in dogs. Initially, clinical signs of KCS include blepharospasm caused by ocular
      pain, mucoid to mucopurulent ocular discharge, and conjunctival hyperemia;
      secondary bacterial infection may also occur, with chronicity, corneal epithelial
      hyperplasia, pigmentation, neovascularization, and corneal ulceration. The
      diagnosis of KCS is based on the presence of consistent clinical signs and
      measurement of decreased aqueous tear production using the Schirmer tear test.
      Therapy is based on administering the following topical drugs: ocular lubricant,
      mucolytics, antibiotics, corticosteroids, pilocarpine, and immunomodulators.
      These last drugs (eg, cyclosporine, pimecrolimus, and tacrolimus) have
      immunosuppressive activity and stimulate tear production. Furthermore, the nerve
      growth factor is a new subject matter of the research. Although these therapies
      are advantageous, stimulation of natural tear production seems to provide the
      highest recovery in clinical signs and prevention of vision loss. The goal of the
      following article is to describe the recent developments about KCS in dogs
      emphasizing the use of new therapies.

PMID- 30101122
TI  - Methicillin-resistant Staphylococcus aureus colonization and infection risks from
      companion animals: current perspectives.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most
      virulent human pathogens and has also recently been recognized as such in the
      veterinary settings. Companion animals, including dogs, cats, horses, small
      exotic animals, wildlife animals, and livestock, may constitute a reservoir for
      MRSA transmission to humans and vice versa. The evolution, emergence, and risk
      factors for MRSA transmission among colonized or infected animals are reviewed in
      the present paper, and infection control practices are discussed.

PMID- 30101121
TI  - Global epidemiology of canine rabies: past, present, and future prospects.
AB  - The rabies virus, a public health scourge from ancient times, is currently
      responsible for an estimated 59,000 human deaths a year, almost all transmitted
      via dog bites. It causes considerable economic impacts on developing countries,
      primarily in Africa and Asia, which can least afford these losses. However,
      despite its almost 100% case fatality rate, canine rabies is a completely
      preventable disease, and historic examples of canine rabies elimination in the
      developed world attest to this. Over the last decade, programs based on
      eliminating the source of the disease from dogs have shown success in reducing
      the public health burden of canine rabies in developing countries, notably across
      Latin America, and this has contributed to the growing evidence base necessary to
      change attitudes toward the feasibility of global canine rabies elimination. More
      recently, assessments of the current economic burden of canine rabies and the
      potential cost savings achievable through mass dog vaccinations have been added
      to this evidence base. Tools and support are available from the international
      community to help countries move progressively toward canine rabies elimination,
      and there is optimism that global freedom from canine rabies can be achieved
      within the next few decades.

PMID- 30101123
TI  - Longitudinal qualitative evaluation of pharmacist integration into the urgent
      care setting.
AB  - Purpose: To describe the most effective model for managing, educating, and
      training pharmacist advanced clinical practitioners (ACPs) in the urgent care
      center (UCC) setting, role evolution and how to measure their effectiveness.
      Participants and methods: Ethical approval was obtained to perform a qualitative
      longitudinal cohort study in three sites, with three pharmacists in each trained
      as ACPs from 2016 to 2017. ACP role, location, management, mentorship, and
      supervision were locally determined. ACPs attended focus groups (FGs) at 1 and 3
      months (sites 1-3), 6 and 12 months (site 1 only), and the UCC staff were
      interviewed once with a topic guide regarding training, integration, role, and
      impact. Verbatim transcriptions were analyzed thematically. Results: Eight ACP
      FGs and 24 stakeholder interviews produced major themes of communication,
      management, education and training, role, and outcomes. Effective education,
      training, and integration required communication of role to address concerns
      regarding salary differentials, supportive management structure, and multi
      professional learning. ACPs reported that the model of workplace training,
      experiential learning, and university-based education was appropriate. Training
      was better located in the minor injuries and general practitioner areas.
      Recommended measures of effectiveness included patient satisfaction and workload
      transfer. Conclusion: The education and training model was appropriate.
      Communication and management require careful consideration to ensure effective
      integration and role development. Pharmacists were better located initially in
      the minor illness rather than major trauma areas. Quality of patient experience
      resulting from the new role was important in addition to reassurance that the
      role represented a positive contribution to workload.

PMID- 30101125
TI  - Inhibiting the NLRP3 Inflammasome With Methylene Blue as Treatment Adjunct in
      Myelodysplasia.
AB  - Myelodysplasia refers to a group of clonal hematopoietic neoplasms characterized
      by genetic heterogeneity, different clinical behaviors and prognoses. Some of
      this group of bone marrow failure conditions have known external causes, some are
      of unknown origin. Within marrow, intracellular, and extracellular elements of
      the innate immune system are activated and contribute to creation of multiple
      cytogenetic abnormalities and are central to the mode of hematopoietic cell
      failure. Basiorka et al. showed that NLRP3 inflammasome activity is essential to
      the innate immune system's destruction of marrow hematopoietic cells commonly in
      myelodysplasia. In April 2018 Hao et al. reported that methylene blue inhibits
      rat NLRP3 inflammasome function. Methylene blue has been in continuous use in
      humans for over a century. It is associated with an eminently benign side effect
      profile in human use. If as in rodents, methylene blue also inhibits NLRP3
      inflammasome function in human myelodysplasia a trial of adjunctive methylene
      blue treatment in transfusion dependent, low risk myelodysplasia where marrow
      inflammation and apoptosis predominates, would be worth trying. HIGHLIGHTS -
      Cytogenetic abnormalities and innate immune activation are seen in myelodysplasia
      The NLRP3 inflammasome is a core element generating marrow failure of
      myelodysplasia- In April 2018 methylene blue was reported to potently inhibit
      NLRP3 inflammasome function- Methylene blue has benign side effects and has been
      in human use for a century- Study of methylene blue treatment of myelodysplasia
      would be a low-risk intervention.

PMID- 30101124
TI  - The Role of Machine Learning in Knowledge-Based Response-Adapted Radiotherapy.
AB  - With the continuous increase in radiotherapy patient-specific data from
      multimodality imaging and biotechnology molecular sources, knowledge-based
      response-adapted radiotherapy (KBR-ART) is emerging as a vital area for radiation
      oncology personalized treatment. In KBR-ART, planned dose distributions can be
      modified based on observed cues in patients' clinical, geometric, and
      physiological parameters. In this paper, we present current developments in the
      field of adaptive radiotherapy (ART), the progression toward KBR-ART, and examine
      several applications of static and dynamic machine learning approaches for
      realizing the KBR-ART framework potentials in maximizing tumor control and
      minimizing side effects with respect to individual radiotherapy patients.
      Specifically, three questions required for the realization of KBR-ART are
      addressed: (1) what knowledge is needed; (2) how to estimate RT outcomes
      accurately; and (3) how to adapt optimally. Different machine learning algorithms
      for KBR-ART application shall be discussed and contrasted. Representative
      examples of different KBR-ART stages are also visited.

PMID- 30101127
TI  - Prognostic Factors for Elderly Patients Treated With Stereotactic Body Radiation
      Therapy for Pancreatic Adenocarcinoma.
AB  - Introduction: Pancreatic ductal adenocarcinoma (PDAC) commonly presents later in
      life with a median age at diagnosis of 70 years. Unfortunately, elderly patients
      are significantly underrepresented in clinical trials. Stereotactic body
      radiation therapy (SBRT) is a promising treatment modality in this population as
      it has demonstrated excellent local control with minimal toxicity. We aimed to
      determine prognostic factors associated with outcomes in elderly patients treated
      with SBRT. Materials and Methods: Elderly patients older than 70 treated with
      SBRT for PDAC at our institution, from 2004 to 2014 were included. Our primary
      endpoints included overall survival (OS) and local-progression-free survival
      (LPFS). Secondary endpoints included regional-progression-free survival (RPFS),
      distant-progression-free-survival (DPFS) and radiation toxicity. Endpoints were
      analyzed with the Kaplan-Meier method. The association of these survival
      endpoints with risk factors was studied with Cox proportional hazards models.
      Results: We identified 145 patients with 146 lesions of pancreatic adenocarcinoma
      with a median age at diagnosis of 79 (range, 70.1-90.3). SBRT was delivered to a
      median dose of 36 Gy (IQR 24-36). Surgical resection was performed on 33.8% of
      the total patients. Median follow-up was 12.3 months (IQR 6.0-23.3 months) and
      the median survival for the entire cohort 14.0 months with a 2-year OS of 27%.
      Multivariate analysis (MVA) demonstrated surgery [p <= 0.0001, HR 0.29 (95% CI,
      0.16-0.51)] and post-SBRT CA19-9 [p = 0.009, HR 1.0004 (95% CI, 1.0002-1.0005)]
      significantly associated with overall survival. Recurrent lesions [p = 0.0069, HR
      5.1 (95% CI, 1.56-16.64)] and post-SBRT CA19-9 levels [p = 0.0107, HR 1.0005 (95%
      CI, 1.0001-1.0008)] were significantly associated with local control on MVA. For
      the entire cohort, 4.1% experienced acute grade 2+ toxicity, and 2% experienced
      late grade 2+ toxicity at 2 years. Conclusion: This review demonstrates
      prognostic factors in elderly patients with PDAC treated with SBRT. We identified
      surgical resection and post-SBRT CA 19-9 as predictive of overall survival in
      this population. Additionally, we show low acute and late toxicity following SBRT
      in elderly patients.

PMID- 30101126
TI  - The Impact of Serum Glucose, Anti-Diabetic Agents, and Statin Usage in Non-small
      Cell Lung Cancer Patients Treated With Definitive Chemoradiation.
AB  - Introduction: Epidemiologic data indicate diabetes confers an augmented risk of
      lung cancer development, yet the relationship between hyperglycemia, metabolic
      agents, and prognosis is unclear. We analyzed the impact of hyperglycemia, anti
      diabetic agents, and statins on outcomes in non-small cell lung cancer (NSCLC)
      patients undergoing chemoradiation. Method and Materials: In total, data from 170
      patients with stage III NSCLC treated at the University of Pittsburgh Medical
      Center between 2001 and 2014 were obtained for analysis. Kaplan-Meier survival
      analysis was used to estimate time-to-event for overall survival (OS), disease
      free survival, distant metastasis (DM), and loco-regional control (LRC). Blood
      glucose values (n = 2870), statins, and diabetic medications were assessed both
      continuously and categorically in univariable and multivariable Cox proportional
      hazard regression models to estimate hazard ratios and identify prognostic
      factors. Results: Tumor volume was a negative prognostic factor for OS, disease
      free survival, DM, and LRC (p = 0.001). Tumor stage and treatment time were
      associated with increased all-cause mortality. Any glucose measurement >= 130
      mg/dl during treatment (2-year estimate 49.9 vs. 65.8%, p = 0.095) was borderline
      significant for decreased LRC, with similar trends on multivariable analysis (HR
      1.636, p = 0.126) and for OS (HR 1.476, p = 0.130). Statin usage was associated
      with improved 2-year LRC (53.4 vs. 62.4%, p = 0.088) but not with improvements in
      survival. Other glycemic parameters, comorbid diabetes diagnosis, or anti
      diabetic medications were not significantly associated with outcomes.
      Conclusions: There were trends for blood glucose value over 130 mg/dl and statin
      nonuse being associated with inferior prognosis for LRC in stage III NSCLC
      patients; glycemic state, statin usage, and glucose-modulating medications were
      not associated with survival outcomes in multivariable analysis in this
      retrospective database.

PMID- 30101128
TI  - Quantitative Analysis of BRCA1 and BRCA2 Germline Splicing Variants Using a Novel
      RNA-Massively Parallel Sequencing Assay.
AB  - Clinical genetic testing for hereditary breast and ovarian cancer (HBOC) is
      becoming widespread. However, the interpretation of variants of unknown
      significance (VUS) in HBOC genes, such as the clinically actionable genes BRCA1
      and BRCA2, remain a challenge. Among the variants that are frequently classified
      as VUS are those with unclear effects on splicing. In order to address this issue
      we developed a high-throughput RNA-massively parallel sequencing assay-CloneSeq
      capable to perform quantitative and qualitative analysis of transcripts in cell
      lines and HBOC patients. This assay is based on cloning of RT-PCR products
      followed by massive parallel sequencing of the cloned transcripts. To validate
      this assay we compared it to the RNA splicing assays recommended by members of
      the ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant
      Alleles) consortium. This comparison was performed using well-characterized
      lymphoblastoid cell lines (LCLs) generated from carriers of the BRCA1 or BRCA2
      germline variants that have been previously described to be associated with
      splicing defects. CloneSeq was able to replicate the ENIGMA results, in addition
      to providing quantitative characterization of BRCA1 and BRCA2 germline splicing
      alterations in a high-throughput fashion. Furthermore, CloneSeq was used to
      analyze blood samples obtained from carriers of BRCA1 or BRCA2 germline sequence
      variants, including the novel uncharacterized alteration BRCA1 c.5152+5G>T, which
      was identified in a HBOC family. CloneSeq provided a high-resolution picture of
      all the transcripts induced by BRCA1 c.5152+5G>T, indicating it results in
      significant levels of exon skipping. This analysis proved to be important for the
      classification of BRCA1 c.5152+5G>T as a clinically actionable likely pathogenic
      variant. Reclassifications such as these are fundamental in order to offer
      preventive measures, targeted treatment, and pre-symptomatic screening to the
      correct individuals.

PMID- 30101130
TI  - Transoral Robotic Surgery in the Nordic Countries: Current Status and
      Perspectives.
AB  - Background: The five Nordic countries with a population of 27 M people form a
      rather homogenous region in terms of health care. The management of head and neck
      cancer is centralized to the 21 university hospitals in these countries. Our aim
      was to gain an overview of the volume and role of transoral robotic surgery
      (TORS) and to evaluate the need to centralize it in this area as the field is
      rapidly developing. Materials and Methods: A structured questionnaire was sent to
      all 10 Departments of Otorhinolaryngology-Head and Neck Surgery in the Nordic
      countries having an active programme for TORS in December 2017. Results: The
      total cumulative number of performed robotic surgeries at these 10 Nordic centers
      was 528 and varied between 5 and 240 per center. The median annual number of
      robotic surgeries was 38 (range, 5-60). The observed number of annually operated
      cases remained fairly low (<25) at most of the centers. Conclusions: The present
      results showing a limited volume of performed surgeries call for considerations
      to further centralize TORS in the Nordic countries.

PMID- 30101131
TI  - Diagnosis, Pathological Findings, and Clinical Management of Gangliocytic
      Paraganglioma: A Systematic Review.
AB  - Background: Although gangliocytic paraganglioma (GP) is considered a rare benign
      neuroendocrine tumor, cases of mortality have been reported. Occasionally, GP is
      misdiagnosed as neuroendocrine tumor G1, which is associated with a poorer
      prognosis than GP. To avoid such misdiagnoses, it is important to understand the
      clinicopathological characteristics of GP. Thus, herein, we discuss the current
      literature on the clinicopathological characteristics of GP. Methods: We
      conducted a systematic review in accordance with the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses statement. PubMed and Japana Centra
      Revuo Medicina searches were used to identify papers describing GP. Inclusion
      criteria included confirmation of epithelioid, spindle-shaped, and ganglion-like
      cells in the main article and/or figures and whether the paper was cited in other
      studies of GP. Data were collected on age, sex, site of the primary lesion, tumor
      size, treatment, prognosis, lymph node metastasis (LNM), depth of tumor invasion,
      rate of preoperative diagnosis, and clinical symptoms. Results: In total, 162
      papers containing 263 cases of GP met the criteria. The mean age at diagnosis was
      53.5 years. The male-to-female ratio was 157:104. The mean tumor size was 25.7
      mm. The predominant site of the primary tumor was the duodenum (89.7%). The most
      common clinical sign of GP was gastrointestinal bleeding (47.9%). Other signs and
      symptoms of GP included abdominal pain (44.7%), anemia (20.3%), incidental
      findings (12.9%), nausea (6.9%), weight loss (5.5%), general fatigue (5.1%),
      jaundice (4.6%), and incidental autopsy findings (5.1%). LNM was observed in
      11.4% of patients. Liver metastasis was observed in 1.1% of patients. Depth of
      tumor invasion (penetrating beyond the submucosal layer or sphincter of Oddi) was
      by far the most significant risk factor for LNM in patients with GP. This
      suggests, along with histological heterogeneity, that GP may have hamartomatous
      characteristics. Furthermore, immunohistochemical expression of progesterone
      receptor and pancreatic polypeptide were useful in distinguishing between GP and
      neuroendocrine tumor G1, even in small biopsy specimens. Conclusions: We reveal
      the clinicopathological characteristics of GP, including risk factors for LNM,
      differential diagnostic approaches, and improvements in the clinical management
      of this tumor.In addition, GP may have hamartomatous characteristics.

PMID- 30101132
TI  - Liver histology and histochemistry in Wilson disease.

PMID- 30101129
TI  - Microenvironment Cell Contribution to Lymphoma Immunity.
AB  - Lymphoma microenvironment is a complex system composed of stromal cells, blood
      vessels, immune cells as well as extracellular matrix, cytokines, exosomes, and
      chemokines. In this review, we describe the function, localization, and
      interactions between various cellular components. We also summarize their
      contribution to lymphoma immunity in the era of immunotherapy. Publications were
      identified from searching Pubmed. Primary literature was carefully evaluated for
      replicability before incorporating into the review. We describe the roles of
      mesenchymal stem/stromal cells (MSCs), lymphoma-associated macrophages (LAMs),
      dendritic cells, cytotoxic T cells, PD-1 expressing CD4+ tumor infiltrating
      lymphocytes (TILs), T-cells expressing markers of exhaustion such as TIM-3 and
      LAG-3, regulatory T cells, and natural killer cells. While it is not in itself a
      cell, we also include a brief overview of the lymphoma exosome and how it
      contributes to anti-tumor effect as well as immune dysfunction. Understanding the
      cellular players that comprise the lymphoma microenvironment is critical to
      developing novel therapeutics that can help block the signals for immune escape
      and promote tumor surveillance. It may also be the key to understanding
      mechanisms of resistance to immune checkpoint blockade and immune-related adverse
      events due to certain types of immunotherapy.

PMID- 30101134
TI  - Fatal disseminated cytomegalovirus infection with necrotizing oophoritis in a
      patient with acquired immunodeficiency syndrome.
AB  - Disseminated human cytomegalovirus (CMV) disease occurs mainly as a congenital
      infection and among immunocompromised hosts. Patients with acquired
      immunodeficiency syndrome (AIDS) are at increased risk for CMV infection, and the
      most prevalent clinical manifestation is retinitis, followed by colitis,
      esophagitis, pneumonitis, and encephalitis. CMV oophoritis is poorly described in
      the literature with some cases reported in patients with hematological or solid
      malignancies, bone marrow or solid organ transplantation, immunosuppressive
      therapy, and advanced AIDS cases. We report the case of a 61-year-old woman with
      a recent diagnosis of AIDS, which was associated with a wasting syndrome. The
      patient presented with abdominal pain, headache, cutaneous vesicular lesions on
      the abdomen, anemia, lymphopenia, and hyponatremia; she died suddenly on the
      fourth day of hospitalization. The autopsy was performed and demonstrated
      disseminated CMV infection with hemorrhagic encephalitis as the immediate cause
      of death. Additionally, pneumonitis, extensive adrenalitis, ulcerated enteritis,
      focal hepatitis, and necrotizing oophoritis were found.

PMID- 30101133
TI  - Celiac Crisis: an unusual presentation of gluten-sensitive enteropathy.
AB  - Celiac disease (CD)-also known as gluten-sensitive enteropathy-is a chronic,
      genetically predisposing and autoimmune entity with a wide range of clinical
      manifestations triggered by gluten ingestion, which affects 1% of the general
      population. Currently, up to 60% of the diagnosis of CD is in adults due to the
      atypical course of the disease. The severe acute onset of CD-also called celiac
      crisis-is very uncommon and is still not well documented in adults. We report the
      case of a 58-year-old man who presented a 45-day history of subtle-onset diarrhea
      followed by malabsorption syndrome with progressive weight loss, anasarca, and
      electrolyte disturbances. The diagnostic work-up included an upper digestive
      endoscopy, which showed scalloping of the duodenal mucosa with pathological
      features confirmed on biopsies. Specific antibodies were positive, and a
      satisfactory clinical response was obtained once a gluten-free diet was started.
      Celiac crisis is a rare initial presentation of CD characterized by severe
      diarrhea, dehydration, weight loss, hypoproteinemia, and metabolic and
      electrolyte disturbances. Although rare, it should be considered in patients with
      apparently unexplained chronic diarrhea.

PMID- 30101135
TI  - Madelung disease (multiple symmetric lipomatosis).
AB  - Madelung disease or multiple symmetric lipomatosis (MSL) is a rare entity among
      the overgrowth syndromes. It is characterized by painless non-encapsulated and
      symmetric fatty deposits in the neck, torso, mammary, and abdominal areas, and in
      the upper and lower limbs. The etiology of the disease is still unknown. Chronic
      alcohol consumption may play a role in adipocyte hyperplasia in genetically
      susceptible individuals. Besides the overgrowth of adipose tissue, patients with
      MSL present features of metabolic syndrome. Patients seek medical attention
      usually for esthetic reasons. We present the case of a middle-aged man who sought
      the outpatient clinic complaining of bulging masses in the posterior upper part
      of the thorax, the occipital area, and the neck. The masses grew over a period of
      2 years. The physical examination and imaging study revealed the presence of
      symmetric lipomatosis. A two-step surgical treatment was undertaken for the
      excision of the lipomatous tissue. The postoperative outcome was uneventful with
      satisfactory esthetic results.

PMID- 30101136
TI  - Perioperative myocardial infarction: diagnostic clues and prevention.
AB  - The diagnosis of perioperative myocardial infarction can be missed if the pain is
      masked by postoperative analgesia and the possibility is not considered. This
      report is the case of a patient with a missed diagnosis of perioperative
      myocardial infarction. Myocardial injury and infarction from noncardiac surgery
      is currently the subject of intense interest and research. This report
      illustrates the importance of the diagnosis and suggests clues that can be used
      to make the diagnosis.

PMID- 30101137
TI  - Calcified fibrous pseudotumor with Castleman disease.
AB  - Simultaneous calcified fibrous pseudotumor (CFT) and Castleman disease (CD) is an
      extremely rare association. CD is an uncommon lymphoproliferative disease that
      can arise in various sites of the body, while CFT is a rare type of benign
      fibrous lesion that frequently affects children and young adults, occurring as
      solitary or multiple lesions throughout the human body. Both entities are rare
      and exhibit typical and diverse histomorphological features. We report the case
      of a 15-year-old female patient, who, at the age of 13 had a biopsy performed at
      an external medical center; however, after 4 months the lesion had regrown. This
      lesion was removed with a surgical operation; however, it regrew 2 years later
      and was removed a third time. The results of the latter two biopsies were the
      same: CFT accompanying CD. The histologic examination of the excised lymph node
      and the surrounding tissue showed hyalinized fibrous tissue containing dystrophic
      and psammomatous calcification. In this case, the hyaline vascular type of CD was
      found to be intertwined with a CFT, which hampered the differentiation of whether
      both entities emerged within the lymph node or if the CFT developed from the soft
      tissue and then involved the lymph node. Future studies involving larger case
      series will provide a more precise insight, which should serve to resolve the
      current uncertainty.

PMID- 30101138
TI  - Livedoid vasculopathy: a compelling diagnosis.

PMID- 30101139
TI  - Juvenile-onset recurrent respiratory papillomatosis with pulmonary involvement
      and carcinomatous transformation.
AB  - Papilloma associated with recurrent respiratory papillomatosis (RRP), caused by
      human papilloma virus (HPV) infection types 6 and 11, is the most common benign
      neoplasm of the larynx. The clinical features of RRP vary widely from mild to
      aggressive forms. RRP in children is known as juvenile-onset recurrent
      respiratory papillomatosis (JORRP). Its outcome may be poor or even fatal due to
      the high rate of recurrence and eventual spread to the entire respiratory tract.
      Pulmonary invasion is reported to occur in 3.3% of patients with RRP, and
      malignant transformation in 0.5% of patients. We report the case of a 39-year-old
      female patient with a diagnosis of JORRP from the age of 3 years, with extensive
      bilateral pulmonary involvement and malignant transformation. Analysis of the
      papilloma and carcinomatous tissues revealed the presence of HPV type 11, which
      is associated with rapid and aggressive progression. We discussed the case on the
      basis of a literature review on pulmonary invasion, malignant transformation, and
      HPV 11 aggressiveness.

PMID- 30101140
TI  - Solitary extranodal Rosai-Dorfman disease of the mandible: an exceedingly rare
      presentation.
AB  - Sinus histiocytosis with massive lymphadenopathy, generally known by the name of
      Rosai-Dorfman disease is a rare benign condition principally affecting cervical
      lymph nodes. Concurrent extra-nodal disease frequently occurs, however, solitary
      extra-nodal disease involving the mandible is exceedingly rare with less than
      five reported cases in the English literature. We describe a case of primary
      involvement of the mandible in a 27-year-old female, and discuss the differential
      diagnosis of this disease with other histiocytic lesions.

PMID- 30101141
TI  - Incomplete Refractory Kawasaki Disease in an Infant-A Case Report and a Review of
      the Literature.
AB  - Kawasaki disease (KD) is a febrile vasculitis, which is commonly defined by fever
      and at least four specific clinical symptoms. Incomplete KD is defined by
      suggestive echocardiographic findings with an incomplete clinical picture.
      Refractory KD is diagnosed in patients resistant to intravenous immunoglobulin
      (IVIG). We report the case of a 6-month-old male infant admitted to our clinic
      for persistent fever and onset of a generalized polymorphous rash, accompanied by
      high fever, rhinorrhea, and cough for the past 7 days. The laboratory tests, on
      the day of admission, revealed leukocytosis with neutrophilia, anemia,
      thrombocytosis, hypernatremia, hypoalbuminemia, elevated C-reactive protein
      (CRP), and erythrocyte sedimentation rate (ESR). Echocardiography showed dilation
      of the left anterior descending coronary artery (LAD). Based on all these
      findings, we established the diagnosis of KD, and we initiated IVIG and
      intravenous pulsed methylprednisolone, with an initial favorable outcome.
      However, the symptoms reappeared, and we administered a second higher single dose
      of IVIG, but without any clinical improvement. Moreover, the laboratory
      parameters and echocardiographic findings worsened. We reinitiated a longer
      course of intravenous methylprednisolone in a smaller dose, which had a favorable
      impact on the clinical, laboratory, and echocardiographic parameters. Multiple
      uncertainties exist related to the management of refractory KD despite the wide
      spectrum of therapeutic options that have been proposed. Our case demonstrates
      that in patients refractory to aggressive initial therapy, low or moderate doses
      of steroid given daily may be helpful.

PMID- 30101143
TI  - Rates of Reactions as a Mathematical Consequence of the Permanence of Atoms and
      the Role of Independent Reactions in the Description of Reaction Kinetics.
AB  - Linear algebra treatment of the permanence of atoms (mass conservation) naturally
      leads to the transformation of formation or destruction rates of components of a
      reaction mixture into rates of reaction steps, which are sufficient to describe
      the transformations mathematically. These steps form a scheme of independent
      reactions that can provide a rational basis for elucidating the reaction
      mechanism (network) while reducing both the component and parametric
      dimensionality of the description of kinetics. Several particular reaction
      examples are used to explain the method and show that rates of additional,
      dependent reactions cannot be unambiguously related to measured component rates.
      They also illustrate how the rates of dependent reactions can be correctly
      expressed in terms of the rates of independent reactions. The method starts only
      with a knowledge of the components of a reaction mixture. It is argued that the
      design of consistent reaction networks or mechanisms should take into account not
      only chemistry but also mathematics.

PMID- 30101142
TI  - Health Economic Evaluations of Cancer in Brazil: A Systematic Review.
AB  - : Background: A large number of health economic evaluation (HEE) studies have
      been published in developed countries. However, Brazilian HEE literature in
      oncology has not been studied. OBJECTIVE: To investigate whether the scientific
      literature has provided a set of HEE in oncology capable of supporting decision
      making in the Brazilian context. Methods: A systematic review was conducted to
      identify and characterize studies in this field. We searched multiple databases
      selecting partial and full HEE studies in oncology (1998-2013). Results: Fifty
      five articles were reviewed, of these, 33 (60%) were full health economic
      evaluations. Type of cancers most frequently studied were: breast (38.2%),
      cervical (14.6%), lung (10.9%) and colorectal (9.1%). Procedures (47.3%) were the
      technologies most frequently evaluated. In terms of the intended purposes of the
      technologies, most (63.6%) were treatments. The majority of the incremental cost
      effectiveness ratios (ICERs) reported have been below the cost-effectiveness
      threshold suggested by the World Health Organization (WHO). Conclusions: There
      has been an increase in the number of HEEs related to cancer in Brazil. These
      studies may support decision-making processes regarding the coverage of and
      reimbursement of healthcare technologies for cancer treatment in Brazil.

PMID- 30101144
TI  - Brasilianoids A-F, New Meroterpenoids From the Sponge-Associated Fungus
      Penicillium brasilianum.
AB  - 3,5-Dimethylorsellinic acid (DMOA) derived meroterpenoids comprise an unique
      class of natural products with diverse scaffolds and with a broad spectrum of
      bioactivities. Bioinformatics analysis of the gene clusters in association with
      the qRT-PCR detection of the amplification of two key genes led to speculate that
      the sponge associated fungus Penicillium brasilianum WZXY-m122-9 is a potential
      producer of meroterpenoids. Chromatographic separation of the EtOAc extract of
      this fungal strain on a large-scale fermentation resulted in the isolation of six
      new DMOA-related meroterpenoids with trivial names of brasilianoids A-F (1-6),
      together with preaustinoid D and preaustinoid A2. The structures were determined
      by extensive analyses of spectroscopic data, including the X-ray diffraction and
      the ECD data for configurational assignment. Brasilianoids A and F showed an
      unprecedented skeleton with a gamma-lactone in ring A, while brasilianoids B-C
      featured a 7/6/6/5/5 pentacyclic ring system finding in nature for the first
      time. The biosynthetic relationship among the isolated compounds was postulated.
      Compound 1 significantly stimulated the expression of filaggrin and caspase-14 in
      HaCaT cells in dose-dependent manner, while compounds 2 and 3 showed moderate
      inhibition against NO production in LPS-induced RAW 264.7 macrophages.

PMID- 30101145
TI  - Divergent Roles for TRAIL in Lung Diseases.
AB  - The tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a widely
      expressed cytokine that can bind five different receptors. TRAIL has been of
      particular interest for its proposed ability to selectively induce apoptosis in
      tumour cells. However, it has also been found to regulate a wide variety of non
      canonical cellular effects including survival, migration and proliferation via
      kinase signalling pathways. Lung diseases represent a wide range of conditions
      affecting multiple tissues. TRAIL has been implicated in several biological
      processes underlying lung diseases, including angiogenesis, inflammation, and
      immune regulation. For example, TRAIL is detrimental in pulmonary arterial
      hypertension-it is upregulated in patient serum and lungs, and drives the
      underlying proliferative pulmonary vascular remodelling in rodent models.
      However, TRAIL protects against pulmonary fibrosis in mice models-by inducing
      apoptosis of neutrophils-and reduced serum TRAIL is found in patients.
      Conversely, in the airways TRAIL positively regulates inflammation and immune
      response. In COPD patients and asthmatic patients challenged with antigen, TRAIL
      and its death receptors are upregulated in serum and airways. Furthermore, TRAIL
      deleted mouse models have reduced airway inflammation and remodelling. In the
      context of respiratory infections, TRAIL assists in immune response, e.g., via T
      cell toxicity in influenza infection, and neutrophil killing in S. pneumoniae
      infection. In this mini-review, we examine the functions of TRAIL and highlight
      the diverse roles TRAIL has in diseases affecting the lung. Disentangling the
      facets of TRAIL signalling in lung diseases could help in understanding their
      pathogenic processes and targeting novel treatments.

PMID- 30101146
TI  - Morphogenesis of Canine Chiari Malformation and Secondary Syringomyelia:
      Disorders of Cerebrospinal Fluid Circulation.
AB  - Chiari-like Malformation (CM) and secondary syringomyelia (SM), as well as their
      analogous human conditions, is a complex developmental condition associated with
      pain and accompanying welfare concerns. CM/SM is diagnosed ever more frequently,
      thanks in part to the increased availability of magnetic resonance imaging in
      veterinary medicine. Research over the last two decades has focused primarily on
      its pathophysiology relating to overcrowding of the cranial caudal fossa. More
      recent characterizations of CM/SM include brachycephaly with osseous reduction
      and neural parenchymal displacement involving the entire brain and craniocervical
      junction to include rostral flattening, olfactory bulb rotation, increased height
      of the cranium, reduced cranial base with spheno-occipital synchondrosis
      angulation, reduced supraoccipital and interparietal crest and rostral
      displacement of the axis and atlas with increased odontoid angulation. The most
      shared manifestation of CM is the development of fluid-filled pockets (syrinx,
      syringes) in the spinal cord that can be readily quantified. Dogs with
      symptomatic CM without SM have a reduced basioccipital bone, compensatory
      increased cranial fossa height with displaced parenchyma whereby the cerebellum
      is invaginated beneath the occipital lobes but without compromising cerebrospinal
      fluid channels enough to cause SM. Thus, broadly defined, CM might be described
      as any distortion of the skull and craniocervical junction which compromises the
      neural parenchyma and cerebrospinal fluid circulation causing pain and/or SM. The
      etiology of CM is multifactorial, potentially including genetically-influenced,
      breed-specific abnormalities in both skeletal and neural components. Since
      causation between specific morphologic changes and SM or clinical signs is
      unproven, CM might be more appropriately considered as a brachycephalic
      obstructive CSF channel syndrome (BOCCS) rather than a single malformation.
      Understanding the normal development of the brain, skull and craniocervical
      junction is fundamental to identifying deviations which predispose to CM/SM. Here
      we review its anatomical, embryological, bio-mechanical, and genetic
      underpinnings to update the profession's understanding of this condition and
      meaningfully inform future research to diminish its welfare impact.

PMID- 30101149
TI  - Corrigendum: Clinical Presentation, Causes, Treatment, and Outcome of Lip
      Avulsion Injuries in Dogs and Cats: 24 Cases (2001-2017).
AB  - [This corrects the article DOI: 10.3389/fvets.2018.00144.].

PMID- 30101147
TI  - Lack of Transmission of Foot-and-Mouth Disease Virus From Persistently Infected
      Cattle to Naive Cattle Under Field Conditions in Vietnam.
AB  - Foot-and-mouth disease (FMD), caused by FMD virus (FMDV; Aphthovirus,
      Picornaviridae), is a highly contagious and economically important disease of
      cloven-hoofed domestic livestock and wildlife species worldwide. Subsequent to
      the clinical phase of FMD, a large proportion of FMDV-infected ruminants become
      persistently infected carriers, defined by detection of FMDV in oropharyngeal
      fluid (OPF) samples 28 days or more post-infection. The goal of this prospective
      study was to characterize the FMD carrier state in cattle subsequent to natural
      infection under typical husbandry practices in Vietnam. Ten persistently infected
      cattle on eight farms in the Long An province in southern Vietnam were monitored
      by monthly screening of serum and oropharyngeal fluid samples for 12 months. To
      assess transmission from FMDV carriers, 16 naive cattle were intentionally
      brought into direct contact with the persistently infected animals for 6 months,
      and were monitored by clinical and laboratory methods. The restricted mean
      duration of the FMD carrier state was 27.7 months, and the rate of decrease of
      the proportion of carrier animals was 0.03 per month. There was no evidence of
      transmission to naive animals throughout the study period. Additionally, there
      was no detection of FMDV infection or seroconversion in three calves born to
      carrier animals during the study. The force of infection for carrier-to-contact
      transmission was 0 per month, with upper 95% confidence limit of 0.064 per month.
      Phylogenetic analysis of viral protein 1 (VP1) coding sequences obtained from
      carriers indicated that all viruses recovered in this study belonged to the O/ME
      SA/PanAsia lineage, and grouped phylogenetically with temporally and
      geographically related viruses. Analysis of within-host evolution of FMDV, based
      upon full-length open reading frame sequences recovered from consecutive samples
      from one animal, indicated that most of the non-synonymous changes occurred in
      Lpro, VP2, and VP3 protein coding regions. This study suggests that the duration
      of FMDV persistent infection in cattle may be longer than previously recognized,
      but the risk of transmission is low. Additional novel insights are provided into
      within-host viral evolution under natural conditions in an endemic setting.

PMID- 30101148
TI  - Recombinant Antibodies in Veterinary Medicine: An Update.
AB  - The production of recombinant antibodies has had a tremendous impact on several
      research fields, most prominently in biotechnology, immunology and medicine,
      enabling enormous advances in each. Thus far, a broad diversity of recombinant
      antibody (rAb) forms have been designed and expressed using different expression
      systems. Even though the majority of rAbs approved for clinical use are targeted
      to humans, advances in veterinary medicine seem promising. The aim of this mini
      review is to present an update regarding the rAbs in veterinary medicine reported
      to date, as well as their potential use in diagnostics, prophylaxis and
      therapeutics. Full- and single-chain fragment variables are the most common forms
      of rAbs developed for the detection, prevention and control of parasitic,
      bacterial and viral diseases, as well as pain and cancer treatment. Nonetheless,
      advances in research seem to be skewed toward economically important animals,
      such as pigs, cows, poultry and dogs. Although significant results have been
      obtained from the rAbs reported here, most have not been developed enough to be
      approved. Further research and clinical trials should be encouraged to enable
      important findings to fulfill their intended potential to improve animal well
      being.

PMID- 30101150
TI  - Genetically Corrected iPSC-Derived Neural Stem Cell Grafts Deliver Enzyme
      Replacement to Affect CNS Disease in Sanfilippo B Mice.
AB  - Sanfilippo syndrome type B (mucopolysaccharidosis type IIIB [MPS IIIB]) is a
      lysosomal storage disorder primarily affecting the brain that is caused by a
      deficiency in the enzyme alpha-N-acetylglucosaminidase (NAGLU), leading to
      intralysosomal accumulation of heparan sulfate. There are currently no treatments
      for this disorder. Here we report that, ex vivo, lentiviral correction of Naglu-/
      neural stem cells derived from Naglu-/- mice (iNSCs) corrected their lysosomal
      pathology and allowed them to secrete a functional NAGLU enzyme that could be
      taken up by deficient cells. Following long-term transplantation of these
      corrected iNSCs into Naglu-/- mice, we detected NAGLU activity in the majority of
      engrafted animals. Successfully transplanted Naglu-/- mice showed a significant
      decrease in storage material, a reduction in astrocyte activation, and complete
      prevention of microglial activation within the area of engrafted cells and
      neighboring regions, with beneficial effects extending partway along the
      rostrocaudal axis of the brain. Our results demonstrate long-term engraftment of
      iNSCs in the brain that are capable of cross-correcting pathology in Naglu-/-
      mice. Our findings suggest that genetically engineered iNSCs could potentially be
      used to deliver enzymes and treat MPS IIIB.

PMID- 30101151
TI  - A Library-Based Screening Strategy for the Identification of DARPins as Ligands
      for Receptor-Targeted AAV and Lentiviral Vectors.
AB  - Delivering genes selectively to the therapeutically relevant cell type is among
      the prime goals of vector development. Here, we present a high-throughput
      selection and screening process that identifies designed ankyrin repeat proteins
      (DARPins) optimally suited for receptor-targeted gene delivery using adeno
      associated viral (AAV) and lentiviral (LV) vectors. In particular, the process
      includes expression, purification, and in situ biotinylation of the extracellular
      domains of target receptors as Fc fusion proteins in mammalian cells and the
      selection of high-affinity binders by ribosome display from DARPin libraries each
      covering more than 1012 variants. This way, DARPins specific for the glutamate
      receptor subunit GluA4, the endothelial surface marker CD105, and the natural
      killer cell marker NKp46 were generated. The identification of DARPins best
      suited for gene delivery was achieved by screening small-scale vector
      productions. Both LV and AAV particles displaying the selected DARPins transduced
      only cells expressing the corresponding target receptor. The data confirm that a
      straightforward process for the generation of receptor-targeted viral vectors has
      been established. Moreover, biochemical analysis of a panel of DARPins revealed
      that their functional cell-surface expression as fusion proteins is more relevant
      for efficient gene delivery by LV particles than functional binding affinity.

PMID- 30101152
TI  - Bioengineered Viral Platform for Intramuscular Passive Vaccine Delivery to Human
      Skeletal Muscle.
AB  - Skeletal muscle is ideal for passive vaccine administration as it is easily
      accessible by intramuscular injection. Recombinant adeno-associated virus (rAAV)
      vectors are in consideration for passive vaccination clinical trials for HIV and
      influenza. However, greater human skeletal muscle transduction is needed for
      therapeutic efficacy than is possible with existing serotypes. To bioengineer
      capsids with therapeutic levels of transduction, we utilized a directed evolution
      approach to screen libraries of shuffled AAV capsids in pools of surgically
      resected human skeletal muscle cells from five patients. Six rounds of evolution
      were performed in various muscle cell types, and evolved variants were validated
      against existing muscle-tropic serotypes rAAV1, 6, and 8. We found that evolved
      variants NP22 and NP66 had significantly increased primary human and rhesus
      skeletal muscle fiber transduction from surgical explants ex vivo and in various
      primary and immortalized myogenic lines in vitro. Importantly, we demonstrated
      reduced seroreactivity compared to existing serotypes against normal human serum
      from 50 adult donors. These capsids represent powerful tools for human skeletal
      muscle expression and secretion of antibodies from passive vaccines.

PMID- 30101153
TI  - UM171 Enhances Lentiviral Gene Transfer and Recovery of Primitive Human
      Hematopoietic Cells.
AB  - Enhanced gene transfer efficiencies and higher yields of transplantable
      transduced human hematopoietic stem cells are continuing goals for improving
      clinical protocols that use stemcell-based gene therapies. Here, we examined the
      effect of the HSC agonist UM171 on these endpoints in both in vitro and in vivo
      systems. Using a 22-hr transduction protocol, we found that UM171 significantly
      enhances both the lentivirus-mediated transduction and yield of CD34+ and
      CD34+CD45RA- hematopoietic cells from human cord blood to give a 6-fold overall
      higher recovery of transduced hematopoietic stem cells, including cells with long
      term lympho-myeloid repopulating activity in immunodeficient mice. The ability of
      UM171 to enhance gene transfer to primitive cord blood hematopoietic cells
      extended to multiple lentiviral pseudotypes, gamma retroviruses, and non
      integrating lentiviruses and to adult bone marrow cells. UM171, thus, provides an
      interesting reagent for improving the ex vivo production of gene-modified cells
      and for reducing requirements of virus for a broad range of applications.

PMID- 30101154
TI  - A Bovine Adenoviral Vector-Based H5N1 Influenza -Vaccine Provides Enhanced
      Immunogenicity and Protection at a Significantly Low Dose.
AB  - Several human and nonhuman adenovirus (AdV) vectors including bovine AdV type 3
      (BAdV-3) were developed as gene delivery vectors to supplement and/or elude human
      AdV (HAdV)-specific neutralizing antibodies (vector immunity). Here we evaluated
      the vaccine immunogenicity and efficacy of BAdV-3 vector (BAd-H5HA) expressing
      hemagglutinin (HA) of a H5N1 influenza virus in a dose escalation study in mice
      with the intranasal (IN) or intramuscular (IM) route of inoculation in comparison
      with the HAdV type C5 (HAdV-C5) vector (HAd-H5HA) expressing HA of a H5N1
      influenza virus. Dose-related increases in the immune responses were clearly
      noticeable. A single IM inoculation with BAd-H5HA resulted in enhanced cellular
      immune responses compared with that of HAd-H5HA and conferred complete protection
      following challenge with a heterologous H5N1 virus at the dose of 3 * 107 plaque
      forming units (PFUs), whereas a significant amount of influenza virus was
      detected in the lungs of mice immunized with 1 * 108 PFUs of HAd-H5HA. Similarly,
      compared with that of HAd-H5HA, a single IN inoculation with BAd-H5HA produced
      significantly enhanced humoral (HA-specific immunoglobulin [IgG] and its
      subclasses, as well as HA-specific IgA) and cellular immune responses, and
      conferred complete protection following challenge with a heterologous H5N1 virus.
      Complete protection with BAd-H5HA was observed with the lowest vaccine dose (1 *
      106 PFUs), but similar protection with HAd-H5HA was observed at the highest
      vaccine dose (1 * 108 PFUs). These results suggest that at least 30-fold dose
      sparing can be achieved with BAd-H5HA vector compared with HAd-H5HA vaccine
      vector.

PMID- 30101155
TI  - Two Different Methods of Quantification of Oxidized Nicotinamide Adenine
      Dinucleotide (NAD+) and Reduced Nicotinamide Adenine Dinucleotide (NADH)
      Intracellular Levels: Enzymatic Coupled Cycling Assay and Ultra-performance
      Liquid Chromatography (UPLC)-Mass Spectrometry.
AB  - Current studies on the age-related development of metabolic dysfunction and
      frailty are each day in more evidence. It is known, as aging progresses,
      nicotinamide adenine dinucleotide (NAD+) levels decrease in an expected
      physiological process. Recent studies have shown that a reduction in NAD+ is a
      key factor for the development of age-associated metabolic decline. Increased
      NAD+ levels in vivo results in activation of pro-longevity and health span
      related factors. Also, it improves several physiological and metabolic parameters
      of aging, including muscle function, exercise capacity, glucose tolerance, and
      cardiac function in mouse models of natural and accelerated aging. Given the
      importance of monitoring cellular NAD+ and NADH levels, it is crucial to have a
      trustful method to do so. This protocol has the purpose of describing the NAD+
      and NADH extraction from tissues and cells in an efficient and widely applicable
      assay as well as its graphic and quantitative analysis.

PMID- 30101156
TI  - Computed diffusion weighted imaging (cDWI) and voxelwise-computed diffusion
      weighted imaging (vcDWI) for oncologic liver imaging: A pilot study.
AB  - Objective: Aim of the study was to evaluate the influence of the selection of
      measured b-values on the precision of cDWI in the upper abdomen as well as on the
      lesion contrast of PET-positive liver metastases in cDWI and vcDWI. Methods: We
      performed a retrospective analysis of 10 patients (4 m, 63.5 +/- 12.9 y/o) with
      PET-positive liver metastases examined in 3 T-PET/MRI with b = 100,600,800,1000
      and 1500s/mm2. cDWI (cb1000/cb1500) and vcDWI were computed based on following
      combinations: i) b = 100/600 s/mm2, ii) b = 100/800 s/mm2, iii) b =
      100/1000s/mm2, iv) b = 100/600/1000s/mm2 v) all measured b-values. Mean signal
      intensity (SI) and standard deviation (SD) in the liver, spleen, kidney, bone
      marrow and in liver lesions were acquired. The coefficient of variation (CV =
      SD/SI), the differences of SI between measured and calculated high b-value images
      and the lesion contrast (SI lesion/liver) were computed. Results: With increasing
      upper measured b-values, the CV in cDWI and vcDWI decreased (CV in the liver in
      cb1500: 0.42 with b100/600 s/mm2 and 0.28 with b100/b1000s/mm2) while the
      differences of measured and calculated b-value images decreased (in the liver in
      cb1500: 30.7% with b = 100/600 s/mm2, 19.7% with b100/b1000s/mm2). In diffusion
      restricted lesions, lesion contrast was at least 1.6 in cb1000 and 1.4 in cb1500,
      respectively, with an upper measured b-value of b = 800 s/mm2 and 2.1 for vcDWI
      with an upper measured b-value of b = 1000s/mm2. Overall, the lesion contrast was
      superior in cb1500 and vcDWI compared to cb1000 (15% and 11%, respectively).
      Conclusion: Measuring higher upper b-values seems to lead to more precise
      computed high b-value images and a decrease of CV. vcDWI provides a comparable
      lesion contrast to b = 1500s/mm2 and offers additionally the reduction of T2
      shine-through effects. For vcDWI, measuring b = 1000s/mm2 as upper b-value seems
      to be necessary to guarantee good lesion visibility in the liver based on our
      preliminary results.

PMID- 30101158
TI  - Data on the Amphidinium carterae Dn241EHU isolation and morphological and
      molecular characterization.
AB  - We present the data corresponding to the isolation and morphological and
      molecular characterization of a strain of Amphidinium carterae, isolated in
      Mallorca Island waters and now deposited in the microalgae culture collection of
      the Plant Biology and Ecology Department of the University of the Basque Country
      under the reference Dn241Ehu. The morphological characterization was made using
      two different techniques of microscopy and the molecular characterization by
      using the 28S rDNA sequences of D1 and D2 domains. This strain has been used for
      a culture study in an indoor LED-lighted pilot-scale raceway to determine its
      production of carotenoids and fatty acids, "Long-term culture of the marine
      dinoflagellate microalga Amphidinium carterae in an indoor LED-lighted raceway
      photobioreactor: Production of carotenoids and fatty acids." (Molina-Miras et
      al., 2018) [1].

PMID- 30101157
TI  - Frequency-selective non-linear blending for the computed tomography diagnosis of
      acute gangrenous cholecystitis: Pilot retrospective evaluation.
AB  - Purpose: To compare the diagnostic performance of frequency-selective non-linear
      blending and conventional linear blending contrast-enhanced CT for the diagnosis
      of acute (AC) and gangrenous (GC) cholecystitis. Materials and methods: Following
      local ethics committee approval for retrospective data analysis, a database
      search derived 39 patients (26 men, mean age 67.8 +/- 14.6 years) with clinical
      signs of acute cholecystitis, contrast enhanced CT (CECT) evaluation,
      cholecystectomy, and pathological examination of the resected specimen. The
      interval between CECT and surgery was 4.7 +/- 4.1 days. Pathological gross
      examination was used to categorize the cases into AC and GC. Subsequently, two
      radiologists categorized the CECT studies in a blinded and independent fashion
      into AC and GC, during two different reading sessions using linear blending and
      frequency-selective non-linear blending CECT. Results: Histologic analysis
      diagnosed 31/39 (79.4%) cases of GC and 8/39 (20.6%) cases of AC. Image
      interpretation of linear blending CECT resulted in classification of 7/39 (17.9%)
      patients as GC and 32/39 (82.1%) as AC, whereas image interpretation of frequency
      selective non-linear blending CECT resulted in classification of 29/39 (74.3%)
      patients as GC and 10/39 (25.7%) as AC. Sensitivity/specificity/PPV/NPV for
      detection of GC were 22.6%/100%/100%/25% with linear blending CECT and
      80.6%/50%/86.2%/40% with frequency-selective non-linear blending CECT,
      respectively. Based on the histopathologic diagnosis frequency-selective non
      linear blending had a significant improvement (p > 0.0001) in the diagnostic
      accuracy of gangrenous cholecystitis compared with linear blending. Conclusion:
      Frequency-selective non-linear blending post-processing increases the diagnostic
      accuracy of gangrenous cholecystitis owing to improved visualization of absence
      of focal enhancement and mural ulcerations.

PMID- 30101159
TI  - Data set on optimized biodiesel production and formulation of emulsified
      Eucalyptus teriticornisis biodiesel for usage in compression ignition engine.
AB  - This data article presents the experimental values pertaining to the bio-oil
      extraction, optimizing biodiesel production and formulation of emulsified fuel
      blends of E.tereticornisis bio-oil for its use in compression ignition engine.
      The E.tereticornisis leaves were collected from the interior region of
      Puducherry, India. Soxhlet extraction process, in the presence of n-hexane,
      yielded 5.2% of bio-oil. Based on the free fatty acid content, base catalysed
      transesterification process was adopted along with use of sodium hydroxide and
      methanol. Optimization of biodiesel yield was carried out by varying the
      operating parameters. A biodiesel yield of 74.19% was obtained at eighty minutes
      reaction duration, 1.8 l/g ms of sodium hydroxide, 70  degrees C reaction
      temperature and 8:1 oil to molar ratio. Furthermore, the physiochemical
      properties improved by emulsifying the obtained biodiesel with 5% of water in
      presence of surfactant through experiments carried out based on Taguchi's DOE
      method.

PMID- 30101160
TI  - Data for vancomycin elution, activity and impact on mechanical properties when
      incorporated into orthopedic bone cement.
AB  - In this article, we report data on the antibiotic elution and efficacy, and
      mechanical properties of Palacos bone cement with different amounts of added
      vancomycin (0.0, 0.125, 0.25, 0.5, 1.0, 2.0 g), see "Vancomycin elution, activity
      and impact on mechanical properties when added to orthopedic bone cement" (Bishop
      et al., 2018) [1]. Mechanical testing was performed for four-point bending,
      compression, and fracture toughness. The release characteristics of vancomycin
      was recorded for up to 60 days to estimate the elution profile. The eluted
      vancomycin efficacy at eliminating the four most common causative orthopedic
      implant pathogens is also reported.

PMID- 30101161
TI  - Sustainability indicators for salmon aquaculture.
AB  - In this paper, we present and describe data comprising indicators of
      sustainability, collected from eight of the major certification schemes for
      salmon aquaculture and categorized according to the topics covered by each. These
      indicators cover most aspects of aquaculture production, including biotic and
      abiotic effects, feed, emission and waste, fish health and welfare, social
      assurance, and respect for native culture. In addition to being published in its
      entirety as supplementary material alongside this article, the data is available
      through a searchable database on the SustainFish project site:
      https://sustainfish.wixsite.com/sustainfishproject/search-indicator-database.

PMID- 30101162
TI  - Exploration of daily Internet data traffic generated in a smart university
      campus.
AB  - In this data article, a robust data exploration is performed on daily Internet
      data traffic generated in a smart university campus for a period of twelve
      consecutive (12) months (January-December, 2017). For each day of the one-year
      study period, Internet data download traffic and Internet data upload traffic at
      Covenant University, Nigeria were monitored and properly logged using required
      application software namely: FreeRADIUS; Radius Manager Web application; and
      Mikrotik Hotspot Manager. A comprehensive dataset with detailed information is
      provided as supplementary material to this data article for easy research utility
      and validation. For each month, descriptive statistics of daily Internet data
      download traffic and daily Internet data upload traffic are presented in tables.
      Boxplot representations and time series plots are provided to show the trends of
      data download and upload traffic volume within the smart campus throughout the 12
      month period. Frequency distributions of the dataset are illustrated using
      histograms. In addition, correlation and regression analyses are performed and
      the results are presented using a scatter plot. Probability Density Functions
      (PDFs) and Cumulative Distribution Functions (CDFs) of the dataset are also
      computed. Furthermore, Analysis of Variance (ANOVA) and multiple post-hoc tests
      are conducted to understand the statistical difference(s) in the Internet traffic
      volume, if any, across the 12-month period. The robust data exploration provided
      in this data article will help Internet Service Providers (ISPs) and network
      administrators in smart campuses to develop empirical model for optimal Quality
      of Service (QoS), Internet traffic forecasting, and budgeting.

PMID- 30101163
TI  - Corporate governance data of 6 Asian economies (2010-2017).
AB  - This article contains firm-level data on 1) aggregated corporate governance
      score, and 2) financial data for the period 2010-2017. The study includes 626
      companies from 6 Asian countries: China, India, Indonesia, Japan, South Korea and
      Thailand. Aggregated corporate governance score is calculated using 13 firm-level
      attributes: board size, board independence, CEO duality, board meeting
      attendance, independence of audit committee, auditor ratification, independence
      of compensation committee, independence of nomination committee, shareholder
      approved poison pill, dual class unequal voting rights of common shares, staged
      board, diversity of board and board duration. Finally, six firm-level financial
      data are included.

PMID- 30101164
TI  - Dataset on the comparison of synthesized and commercial zeolites for potential
      solar adsorption refrigerating system.
AB  - The purpose of this dataset is to provide a comparison between synthesized and
      commercial 4A and 13X type zeolites. Metakaolin produced from the calcination of
      beneficiated kaolin at 750  degrees C for 4 h was dealuminated using sulphuric
      acid to get the required silica to alumina ratio for the zeolite synthesis.
      Zeolite 4A and 13X samples were characterized along-side with the commercial
      variants using X-ray fluorescence (XRF), X-ray diffraction (XRD), Brunauer,
      Emmett and Teller (BET) and scanning electron microscopy (SEM) techniques. These
      analyses revealed that, the zeolites synthesized are of comparatively acceptable
      quality. The pore size of 120.859 nm, pore volume of 0.0065 cm3/g and surface
      area of 22 m2/g were obtained from BET analyses for zeolite 4A synthesized from
      kaolin, while the commercial zeolite 4A used as control gave pore size of 58.143
      nm, pore volume of 0.2462 cm3/g and surface area of 559.13 m2/g. In the same
      vein, the pore size of 10.5059 nm, pore volume of 0.135847 cm3/g and surface area
      of 324.584 m2/g were obtained from BET analyses for zeolite 13X synthesized from
      kaolin, while the commercial zeolite 13X gave pore size of 7.2752 nm, pore volume
      of 0.135951 cm3/g and surface area of 310.0906 m2/g.

PMID- 30101165
TI  - Contributing to agricultural mix:analysis of the living standard measurement
      study - Integrated survey on agriculture data set.
AB  - The Living Standard Measurement Study- Integrated Survey on Agriculture (LSMS
      ISA) is a General Household Survey (GHS) and a cross-sectional survey consisting
      of 22,000 households which is carried out periodically across the globe.
      Currently, the GHS has three panels consisting of 5000 households of the GHS
      collecting additional data on agricultural activities, other household income
      activities, and household expenditure and consumption, among others. This is to
      improve data from the agricultural sector and the linkage to other facets of
      households' characteristics and outcomes. The LSMS data-set, questionnaire, and
      basic information document are freely available online at:
      http://microdata.worldbank.org/index.php/catalog/2734.

PMID- 30101166
TI  - Traumatic rupture of a solitary splenic hydatid cyst: A case report.
AB  - The rupture of an Echinococcus granulosus hydatid cyst in the spleen due to
      trauma is a rare event. In this case report we describe the case of a 39-year-old
      Lebanese male victim of a motor vehicle accident with a ruptured solitary splenic
      hydatid cyst discovered by CT scan and excised during exploratory laparotomy.
      Echinococcosis or hydatid disease is a parasitic infestation by the Echinococcus
      genus of tapeworm. The eggs of E. granulosus, a species of Echinococcus, are
      fecal-orally transmitted to human hosts, most often from dog feces, and manifest
      as cystic lesions termed hydatid. E. granulosus most commonly affects the liver
      (75%), lungs (15%), and rarely the spleen (2-5%) [1], [2]. E. granulosus is
      particularly endemic to cattle rearing areas of the Middle East. Infected
      patients most commonly present with vague abdominal pain, as a result of mass
      effect or spontaneous rupture of the cyst. Nevertheless, patient presentation may
      be due to traumatic rupture of a hydatid cyst; however, this is very rare. Herein
      we report a case of traumatic rupture of a solitary splenic hydatid cyst in a 39
      year-old male following a motor vehicle crash, managed following the Advanced
      Trauma Life Support (ATLS) protocol.

PMID- 30101167
TI  - Trauma sternotomy for presumed haemopericardium with incidental coccidioidal
      pericarditis.
AB  - Background: Disseminated cocciodiomycosis with extrapulmonary disease occurs in
      less than 1% of infected patients, with few cases involving the pericardium
      reported in the literature. A subxiphoid window in a focussed assessment with
      sonography for trauma is a fast and reliable study for detecting haemopericardium
      in the haemodynamically unstable injured patient. Methods: Case report and
      literature review. Case report: A 50-year old man presented in extremis following
      a stab wound to the right thoracoabdominal region with a positive pericardial
      ultrasound. At the time of emergent sternotomy, the pericardial effusion appeared
      non-traumatic and not the cause of haemodynamic instability. Lung, diaphragm,
      liver and transverse colon lacerations were controlled by laparotomy. He was
      discovered to have extensive adenopathy within the mediastinum, porta hepatis,
      and lesser sac, which after histopathologic examination, demonstrated
      granulomatous lymphadenitis consistent with disseminated cocciodiomycosis.
      Conclusions: This case report describes the first reported "incidental"
      pericardial effusion in a haemodynamically unstable patient sustaining a
      thoracoabdominal stab wound discovered on a positive ultrasound study. Emergent
      operative exploration and subsequent workup determined the pericardial fluid to
      be of infectious origin, rather than traumatic. With the incidence of
      cocciodiomycosis within endemic geographic regions significantly rising,
      coccidioidal pericarditis may become an increasingly relevant cause of fluid
      detected on noninvasive pericardial examination.

PMID- 30101168
TI  - Fracture of a persistent olecranon physis in an adult.
AB  - A persistent olecranon physis is relatively rare; a fracture through the
      persistent olecranon physis in an adult is particularly rare. Little is known
      about the pathology of this disease. We report a case of a 36-year-old man
      presenting with right elbow pain after he had slipped and hit his elbow, with a
      history of a persistent symptomatic olecranon physis when he was a junior high
      school baseball player. He had been diagnosed with a fracture through a
      persistent olecranon physis by another doctor. Ten weeks after the injury, an
      iliac autograft was inserted and internal fixation was achieved with Kirschner
      wires and a figure-of-eight tension band in our hospital. Histologically, a
      fracture passed through the persistent physis cartilage and degeneration of the
      remnant of the physis was observed. The remnant of the physis at the olecranon
      side had not been replaced by new bone, though the physis at the distal ulnar was
      nearly replaced by new bone. The patient returned to work without experiencing
      pain or limitation in the range of motion 6 months after the operation.
      Radiographic evidence of bone union was seen after removal of internal fixation
      at the 13-month follow-up.

PMID- 30101169
TI  - Blunt trauma pancreatic duct injury managed by non-operative technique, a case
      study and literature review.
AB  - We describe the case of a 15 year old boy who presented with generalised
      abdominal pain following a seemingly minor collision at weekend soccer.
      Investigation revealed a grade IV pancreatic injury that was subsequently managed
      with pancreatic stent insertion by endoscopic retrograde cholangiopancreatography
      (ERCP) and total parenteral nutrition (TPN) prior to recommencing low fat diet 10
      days post-injury.

PMID- 30101170
TI  - An unduly delayed presentation of an "isolated segment of ileum" after blunt
      abdominal trauma with full recovery.

PMID- 30101171
TI  - Transcarotid balloon occlusion of the brachiocephalic artery to control bleeding
      due to sharp injuries of the right subclavian artery.
AB  - We present a new manoeuvre of transcarotid balloon occlusion of the
      brachiocephalic artery to control bleeding due to sharp injuries of the right
      subclavian artery. To control the bleeding, we employed a temporary balloon
      occlusion of the brachiocephalic artery with a 6.0 Fogarty balloon catheter,
      which was introduced through ECA retrogradely into the aorta, inflated and pulled
      back. Described manoeuvre is simple, rapid performed, relatively safe and it is
      capable of decreasing the morbidity and mortality rates of patients with sharp
      injuries to the right subclavian artery.

PMID- 30101172
TI  - The use of pedicled abdominal flaps for coverage of acute bilateral
      circumferential degloving injuries of the hand.
AB  - Reconstruction of bilateral soft tissue defects in hand and distal third of the
      forearm, is a challenge for any reconstructive surgeon. When there is
      circumferential skin loss affecting the whole hand and fingers as in major
      degloving injuries, the extent of tissue required for reconstruction narrows down
      the choice of flaps. When the injury affects both hands the magnitude of the
      problem becomes compounded. There is no report in the literature of free skin
      flaps to cover circumferential degloving injuries in both hands. We are
      presenting the technical considerations and outcome of pedicled abdominal flaps
      used for immediate coverage of circumferential degloving injuries of both hands.

PMID- 30101173
TI  - Medial peritalar fracture dislocation of the talar body.
AB  - Peritalar fracture dislocations typically involve the talar neck and are
      classified according to Hawkins. To our knowledge, peritalar fracture dislocation
      involving the talar body has not been formally reported. In this article, we
      describe a case of peritalar fracture dislocation of the talar body.

PMID- 30101174
TI  - Completely thoracoscopic, intra-pleural reduction and fixation of severe rib
      fractures.

PMID- 30101175
TI  - Blunt trauma: An uncommon cause of common bile duct injury.
AB  - Blunt force trauma to the extrahepatic biliary ductal system as a cause of
      avulsion is an uncommon injury associated with wide variability in prognosis.
      These cases are often difficult to identify, primarily as they are complicated by
      trauma patients exhibiting more immediate and obviously life-threatening
      injuries. This case demonstrates a 46 year-old-male involved in a head on motor
      vehicle collision, sustaining blunt force abdominal trauma resulting in partial
      transection of the common bile duct. Injury was discovered incidentally on
      exploratory laparotomy post endovascular repair of abdominal thoracic aortic
      rupture. Open cholescystectomy with intraoperative cholangiogram was performed,
      isolating extravasation from the common bile duct. A 16-French T-tube was placed
      in the common bile duct and two large #24 Jackson-Pratt tubes were placed in the
      vicinity. The procedure was well-tolerated and the patient was discharged with T
      tube in place. Discharge was on postoperative day 28 with removal of tubes on
      postoperative day 54 and the patient was able to make a full recovery.

PMID- 30101176
TI  - Vertical axis dislocation with coronal fracture of the patella: A previously
      unreported injury pattern.
AB  - The patella usually dislocates laterally. Less commonly, intra-articular
      dislocation occurs about either the vertical or horizontal axis. Patellar
      fractures are generally transverse with varying degrees of comminution, and less
      frequently vertical in the sagittal plane. We present a 9-year follow-up of a
      previously undescribed coronal patellar fracture associated with vertical axis
      dislocation of the patella. The mechanism of this severe injury is described.

PMID- 30101177
TI  - Patterns of retroperitoneal trauma following gunshot violence: A case series.
AB  - Introduction: Abdominal trauma is defined as any injury to the abdomen and its
      containing viscera. Common penetrating injuries including gunshot or stab
      injuries are increasing worldwide. However, retroperitoneal gunshot injuries have
      a lower incidence than trans-abdominal trauma and can have substantially
      different outcomes. Case report: We report a series of three family members
      involved in gunshot violence over an18-month period. Each sustained
      retroperitoneal gunshot injuries with varying injuries patterns and treatment
      courses. Interestingly, one patient had a delayed small bowel perforation on day
      6 post injury. Discussion: Retroperitoneal trauma following gun violence has a
      lower incidence than trans-abdominal trauma. There is a paucity of literature
      describing injury patterns following this type of injury and their subsequent
      management. In the context of penetrating retroperitoneal trauma, the
      retroperitoneal organs are at risk and therefore serial clinical and/or
      radiological assessment is necessary. Delayed small bowel injury as a consequence
      of retroperitoneal gunshot is an unusual finding, with no reports to our
      knowledge in the literature. Conclusion: this case series highlight that
      penetrating retroperitoneal trauma can produce a variety of injury patterns.
      Therefore a wide clinical acumen is needed to ensure a successful outcome. The
      trajectory of the bullet may help ascertain potential injuries, but serial
      assessment and observation are also important. Ultimately, individual cases must
      be treated accordingly, based on clinical stability, severity of injury and
      radiological findings. Despite initial stability, patients should always be
      observed for delayed complications.

PMID- 30101178
TI  - Isolated complete jejunal transection following abdominal blunt trauma with
      delayed presentation.
AB  - In blunt trauma, diagnosis of small bowel injury is infrequent and accounts for
      less than 1.1% of blunt trauma admissions. Of those, only 0.3% are perforated.1
      Isolated transection of the jejunum following blunt abdominal trauma has rarely
      been reported in literature.2,3 Most cases of small bowel perforations after
      blunt trauma occur as a result of motor vehicle crashes and falls from heights
      and are often associated with multiple injuries.4 This is a report of a 26 year
      old female that presented 14 h after being involved in a motor vehicle crash and
      was found to have complete transection of her proximal jejunum with underlying
      mesenteric injury. Following the crash, the patient extricated herself from the
      vehicle, went home, and fell asleep with no significant complaints initially
      reported. She woke up hours later with severe abdominal pain and presented to our
      emergency department. CT was performed and revealed free fluid in the abdomen.
      Subsequently, an exploratory laparotomy was performed that revealed complete
      jejunal transection with underlying mesenteric injury. Isolated complete
      transection of the proximal jejunum should be considered in the evaluation of
      patients following blunt abdominal trauma, and presentation may be delayed up to
      14 h. To the best of our knowledge, this is the first case report of complete
      transection of the proximal small bowel following a motor vehicle crash with the
      longest delay in presentation reported in the literature.

PMID- 30101179
TI  - Posterior wall acetabulum fracture-dislocation with subsequent ipsilateral pipkin
      IV fracture-dislocation: How many hits can a hip take?
AB  - The treatment of acetabulum fractures is a technically-demanding task for
      orthopaedic trauma surgeons. The treatment of femoral head fractures associated
      with acetabulum fractures, pipkin IV fractures, presents difficulty as usually
      the femoral head fracture requires treatment through an anterior approach and the
      acetabulum fracture, which is commonly a posterior wall fracture, requires
      treatment through a posterior approach. Recently, surgical dislocation of the hip
      has become an accepted option for treatment of these fractures as it allows
      treatment of the femoral head fracture and posterior wall acetabulum fracture
      through one approach. However, dual anterior and posterior approaches are
      acceptable. We present 15 year follow up of an 18 year old female who underwent
      open reduction internal fixation of a posterior wall acetabulum fracture through
      a Kocher-Langenbeck approach. Four months later the patient sustained a second
      fracture dislocation of the same hip, this time a femoral head fracture with an
      associated posterior wall acetabulum fracture that was treated with a Kocher
      Langenbeck approach for the revision acetabulum and a approach for the femoral
      head fracture. At fifteen years the patient had a Merle d'Aubigne score of 15 and
      a Harris hip score of 71. She was gainfully employed and subjectively happy with
      her surgical result. While treatment of pipkin IV fracture dislocations can be
      treated through a surgical dislocation of the hip, dual surgical approaches are a
      viable option in certain cases.

PMID- 30101180
TI  - Undetected anteromedial coronoid fracture in elbow dislocation: A case report.

PMID- 30101181
TI  - Fixing a fractured arthrodesed hip with rapid prototype templating and minimal
      invasive plate osteosynthesis.
AB  - CASE: We present an elderly lady with an intertrochanteric fracture of a
      previously fused hip. A 3D printed model of her pelvis and femur was used for
      implant templating before surgery. Minimal invasive fixation was performed with a
      spanning reversed distal femur locking plate without the need for removal of the
      previous implant. Multiple long locking screws were placed in the supra
      acetabular region. The patient had union in 4 months, return to function and no
      complication. Conclusion: The technique allowed us to optimize implant selection
      and insert screws safely at difficult trajectories using minimal invasive
      surgery.

PMID- 30101182
TI  - Blunt bilateral diaphragmatic rupture-A right side can be easily missed.
AB  - Blunt diaphragmatic rupture (BDR) is uncommon with a reported incidence range of
      1%-2%. The true incidence is not known. Bilateral BDR is particularly rare. We
      presented a case of bilateral BDR and we think that the incidence is under
      recognised thanks to an easily missed and difficult to diagnose right sided
      injury.

PMID- 30101184
TI  - Penetrating cardiac trauma and the use of emergent extracorporeal membrane
      oxygenation and therapeutic hypothermia: When cooler heads prevail.
AB  - This is a case of penetrating chest trauma with traumatic arrest from cardiac
      tamponade, right and left ventriculotomies, mitral valve injury and ventricular
      septal defect. Patient underwent resuscitative thoracotomy converted to clamshell
      thoracotomy for haemorrhage control. Ventriculotomies were repaired on initial
      damage control operation. Extracorporeal membrane oxygenation cannulation and
      therapeutic cooling bridged to definitive cardiac repair several days later.
      Patient was discharged to an inpatient rehabilitation facility in 16 days.

PMID- 30101183
TI  - Ilizarov frame delayed internal fixation of Lisfranc fracture dislocation with
      severe soft tissue injury: New technique.
AB  - We describe a new technique of temporary stabilisation of a divergent Lisfranc
      fracture dislocation of foot with severe crush injury using an Ilizarov frame. A
      69-year-old man presented with severe crush injury and complete disruption of the
      midfoot. Examination revealed full thickness skin necrosis, haemorrhagic blisters
      and extensive swelling. A staged technique was used with temporary application of
      an Ilizarov frame followed by delayed limited internal fixation. Excellent result
      was achieved with restoration of medial arch, complete pain relief and good
      functional outcome. A staged treatment initially using an Ilizarov frame prior to
      limited internal fixation allows soft tissue to settle in severe crush injury.

PMID- 30101185
TI  - Work status, retirement, and depression in older adults: An analysis of six
      countries based on the Study on Global Ageing and Adult Health (SAGE).
AB  - The aim of the present study was to analyse the association between the
      occurrence of a major depressive episode among older adults and work status in
      low- and medium-income countries. A cross-sectional study was conducted with
      people 60 years of age and older from the six countries (Mexico, India, China,
      Russian Federation, Ghana and South Africa) included in the Study on Global
      Ageing and Adult Health (SAGE) and who participated in its first wave (2009
      2010). The occurrence of a major depressive episode (MDE) over the previous 12
      months was determined based on an adaptation of the ICD-10 diagnostic criteria.
      The association between current work status and the presence of an MDE was
      estimated using binary logistic regression models with country-level fixed
      effects, and interaction terms between the country and work status. Results
      showed the odds of presenting an MDE were lower for older adults who were retired
      with a pension than for those who were currently working, although this
      protective association was observed only for men in China (OR=0.23; CI 95%:0.08
      0.70) and Ghana (OR=0.25; CI 95%:0.07-0.95) and for women in India (OR=0.05; CI
      95%:0.01-0.51) and South Africa (OR=0.19; CI 95%:0.04-0.97). For women, being a
      homemaker also showed a protective association in South Africa (OR=0.09;
      CI95%:0.01-0.66) and Mexico (OR=0.32; CI95%:0.14-0.76). In the case of being
      retired without a pension, no significant association was found in any country.
      The previous indicates that retirement with pension has a protective association
      with MDE only for men in China and Ghana and women in India and South Africa. The
      heterogeneity of this association reflects cultural and socioeconomic differences
      between the analysed countries.

PMID- 30101186
TI  - Synthesis, radiosynthesis, in vitro and first in vivo evaluation of a new matrix
      metalloproteinase inhibitor based on gamma-fluorinated alpha
      sulfonylaminohydroxamic acid.
AB  - Background: To study MMP activity in vivo in disease, several radiolabeled MMP
      inhibitors functioning as radiotracers have been evaluated by means of SPECT and
      PET. Unfortunately, most of them suffer from metabolic instability, mainly
      hepatobiliary clearance and insufficient target binding. The introduction of a
      fluorine atom into MMPIs could contribute to target binding, enhance the
      metabolic stability and might shift the clearance towards more renal elimination.
      Recently developed alpha-sulfonylaminohydroxamic acid based gamma-fluorinated
      inhibitors of MMP-2 and -9 provide promising fluorine interactions with the
      enzyme active site and high MMP inhibition potencies. The aim of this study is
      the (radio)synthesis of a gamma-fluorinated MMP-2 and -9 inhibitor to evaluate
      its potential as a radiotracer to image MMP activity in vivo. Results: Two new
      fluorine-containing, enantiomerically pure inhibitors for MMP-2 and -9 were
      synthesized in a six step sequence. Both enantiomers exhibited equal inhibition
      potencies in the low nanomolar and subnanomolar range. LogD value indicated
      better water solubility compared to the CGS 25966 based analog. The most potent
      inhibitor was successfully radiofluorinated. In vivo biodistribution in wild type
      mice revealed predominantly hepatobiliary clearance. Two major radioactive
      metabolites were found in different organs. Defluorination of the radiotracer was
      not observed. Conclusion: (Radio)synthesis of a CGS based gamma-fluorinated MMP
      inhibitor was successfully accomplished. The (S)-enantiomer, which normally shows
      no biological activity, also exhibited high MMP inhibition potencies, which may
      be attributed to additional interactions of fluorine with enzyme's active site.
      Despite higher hydrophilicity no significant differences in the clearance
      characteristics compared to non-fluorinated MMPIs was observed. Metabolically
      stabilizing effect of the fluorine was not monitored in vivo in wild type mice.

PMID- 30101187
TI  - Combination of IAP Antagonists and TNF-alpha-Armed Oncolytic Viruses Induce Tumor
      Vascular Shutdown and Tumor Regression.
AB  - Smac mimetic compounds (SMCs) are anti-cancer drugs that antagonize Inhibitor of
      Apoptosis proteins, which consequently sensitize cancer cells to death in the
      presence of proinflammatory ligands such as tumor necrosis factor alpha (TNF
      alpha). SMCs synergize with the attenuated oncolytic vesicular stomatitis virus
      (VSVDelta51) by eliciting an innate immune response, which is dependent on the
      endogenous production of TNF-alpha and type I interferon. To improve on this SMC
      mediated synergistic response, we generated TNF-alpha-armed VSVDelta51 to produce
      elevated levels of this death ligand. Due to ectopic expression of TNF-alpha from
      infected cells, a lower viral dose of TNF-alpha-armed VSVDelta51 combined with
      treatment of the SMC LCL161 was sufficient to improve the survival rate compared
      to LCL161 and unarmed VSVDelta51 co-therapy. This improved response is attributed
      to a bystander effect whereby the spread of TNF-alpha from infected cells leads
      to the death of uninfected cells in the presence of LCL161. In addition, the
      treatments induced vascular collapse in solid tumors with a concomitant increase
      of tumor cell death, revealing another mechanism by which cytokine-armed
      VSVDelta51 in combination with LCL161 can kill tumor cells. Our studies
      demonstrate the potential for cytokine-engineered oncolytic virus and SMCs as a
      new combination immunotherapy for cancer treatment.

PMID- 30101188
TI  - Aspirational pursuit of mates in online dating markets.
AB  - Romantic courtship is often described as taking place in a dating market where
      men and women compete for mates, but the detailed structure and dynamics of
      dating markets have historically been difficult to quantify for lack of suitable
      data. In recent years, however, the advent and vigorous growth of the online
      dating industry has provided a rich new source of information on mate pursuit. We
      present an empirical analysis of heterosexual dating markets in four large U.S.
      cities using data from a popular, free online dating service. We show that
      competition for mates creates a pronounced hierarchy of desirability that
      correlates strongly with user demographics and is remarkably consistent across
      cities. We find that both men and women pursue partners who are on average about
      25% more desirable than themselves by our measures and that they use different
      messaging strategies with partners of different desirability. We also find that
      the probability of receiving a response to an advance drops markedly with
      increasing difference in desirability between the pursuer and the pursued.
      Strategic behaviors can improve one's chances of attracting a more desirable
      mate, although the effects are modest.

PMID- 30101189
TI  - Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause
      outbreaks in humans as a result of spillover events from dromedaries. In contrast
      to humans, MERS-CoV-exposed dromedaries develop only very mild infections and
      exceptionally potent virus-neutralizing antibody responses. These strong antibody
      responses may be caused by affinity maturation as a result of repeated exposure
      to the virus or by the fact that dromedaries-apart from conventional antibodies
      have relatively unique, heavy chain-only antibodies (HCAbs). These HCAbs are
      devoid of light chains and have long complementarity-determining regions with
      unique epitope binding properties, allowing them to recognize and bind with high
      affinity to epitopes not recognized by conventional antibodies. Through direct
      cloning and expression of the variable heavy chains (VHHs) of HCAbs from the bone
      marrow of MERS-CoV-infected dromedaries, we identified several MERS-CoV-specific
      VHHs or nanobodies. In vitro, these VHHs efficiently blocked virus entry at
      picomolar concentrations. The selected VHHs bind with exceptionally high affinity
      to the receptor binding domain of the viral spike protein. Furthermore,
      camel/human chimeric HCAbs-composed of the camel VHH linked to a human Fc domain
      lacking the CH1 exon-had an extended half-life in the serum and protected mice
      against a lethal MERS-CoV challenge. HCAbs represent a promising alternative
      strategy to develop novel interventions not only for MERS-CoV but also for other
      emerging pathogens.

PMID- 30101190
TI  - Kisspeptin/GPR54 signaling restricts antiviral innate immune response through
      regulating calcineurin phosphatase activity.
AB  - G protein-coupled receptor 54 (GPR54), the key receptor for the neuropeptide
      hormone kisspeptin, plays essential roles in regulating puberty development and
      cancer metastasis. However, its role in the antiviral innate immune response is
      unknown. We report that virus-induced type I interferon (IFN-I) production was
      significantly enhanced in Gpr54-deficient cells and mice and resulted in
      restricted viral replication. We found a marked increase of kisspeptin in mouse
      serum during viral infection, which, in turn, impaired IFN-I production and
      antiviral immunity through the GPR54/calcineurin axis. Mechanistically,
      kisspeptin/GPR54 signaling recruited calcineurin and increased its phosphatase
      activity to dephosphorylate and deactivate TANK [tumor necrosis factor receptor
      associated factor (TRAF) family member-associated NF-kappaB activator]-binding
      kinase 1 (TBK1) in a Ca2+-dependent manner. Thus, our data reveal a
      kisspeptin/GPR54/calcineurin-mediated immune evasion pathway exploited by virus
      through the negative feedback loop of TBK1 signaling. These findings also provide
      insights into the function and cross-talk of kisspeptin, a known neuropeptide
      hormone, in antiviral innate immune response.

PMID- 30101192
TI  - The environmental niche of the global high seas pelagic longline fleet.
AB  - International interest in the protection and sustainable use of high seas
      biodiversity has grown in recent years. There is an opportunity for new
      technologies to enable improvements in management of these areas beyond national
      jurisdiction. We explore the spatial ecology and drivers of the global
      distribution of the high seas longline fishing fleet by creating predictive
      models of the distribution of fishing effort from newly available automatic
      identification system (AIS) data. Our results show how longline fishing effort
      can be predicted using environmental variables, many related to the expected
      distribution of the species targeted by longliners. We also find that the
      longline fleet has seasonal environmental preferences (for example, increased
      importance of cooler surface waters during boreal summer) and may only be using
      38 to 64% of the available environmentally suitable fishing habitat. Possible
      explanations include misclassification of fishing effort, incomplete AIS
      coverage, or how potential range contractions of pelagic species may have reduced
      the abundance of fishing habitats in the open ocean.

PMID- 30101191
TI  - Microglial pannexin-1 channel activation is a spinal determinant of joint pain.
AB  - Chronic joint pain such as mechanical allodynia is the most debilitating symptom
      of arthritis, yet effective therapies are lacking. We identify the pannexin-1
      (Panx1) channel as a therapeutic target for alleviating mechanical allodynia, a
      cardinal sign of arthritis. In rats, joint pain caused by intra-articular
      injection of monosodium iodoacetate (MIA) was associated with spinal adenosine 5'
      triphosphate (ATP) release and a microglia-specific up-regulation of P2X7
      receptors (P2X7Rs). Blockade of P2X7R or ablation of spinal microglia prevented
      and reversed mechanical allodynia. P2X7Rs drive Panx1 channel activation, and in
      rats with mechanical allodynia, Panx1 function was increased in spinal microglia.
      Specifically, microglial Panx1-mediated release of the proinflammatory cytokine
      interleukin-1beta (IL-1beta) induced mechanical allodynia in the MIA-injected
      hindlimb. Intrathecal administration of the Panx1-blocking peptide 10panx
      suppressed the aberrant discharge of spinal laminae I-II neurons evoked by
      innocuous mechanical hindpaw stimulation in arthritic rats. Furthermore, mice
      with a microglia-specific genetic deletion of Panx1 were protected from
      developing mechanical allodynia. Treatment with probenecid, a clinically used
      broad-spectrum Panx1 blocker, resulted in a striking attenuation of MIA-induced
      mechanical allodynia and normalized responses in the dynamic weight-bearing test,
      without affecting acute nociception. Probenecid reversal of mechanical allodynia
      was also observed in rats 13 weeks after anterior cruciate ligament transection,
      a model of posttraumatic osteoarthritis. Thus, Panx1-targeted therapy is a new
      mechanistic approach for alleviating joint pain.

PMID- 30101193
TI  - Unexpected contribution of lymphatic vessels to promotion of distant metastatic
      tumor spread.
AB  - Tumor lymphangiogenesis is accompanied by a higher incidence of sentinel lymph
      node metastasis and shorter overall survival in several types of cancer. We asked
      whether tumor lymphangiogenesis might also occur in distant organs with
      established metastases and whether it might promote further metastatic spread of
      those metastases to other organs. Using mouse metastasis models, we found that
      lymphangiogenesis occurred in distant lung metastases and that some metastatic
      tumor cells were located in lymphatic vessels and draining lymph nodes. In
      metastasis-bearing lungs of melanoma patients, a higher lymphatic density within
      and around metastases and lymphatic invasion correlated with poor outcome. Using
      a transgenic mouse model with inducible expression of vascular endothelial growth
      factor C (VEGF-C) in the lung, we found greater growth of lung metastases, with
      more abundant dissemination to other organs. Our findings reveal unexpected
      contributions of lymphatics in distant organs to the promotion of growth of
      metastases and their further spread to other organs, with potential clinical
      implications for adjuvant therapies in patients with metastatic cancer.

PMID- 30101194
TI  - Tousled-like kinases stabilize replication forks and show synthetic lethality
      with checkpoint and PARP inhibitors.
AB  - DNA sequence and epigenetic information embedded in chromatin must be faithfully
      duplicated and transmitted to daughter cells during cell division. However, how
      chromatin assembly and DNA replication are integrated remains unclear. We
      examined the contribution of the Tousled-like kinases 1 and 2 (TLK1/TLK2) to
      chromatin assembly and maintenance of replication fork integrity. We show that
      TLK activity is required for DNA replication and replication-coupled nucleosome
      assembly and that lack of TLK activity leads to replication fork stalling and the
      accumulation of single-stranded DNA, a phenotype distinct from ASF1 depletion.
      Consistent with these results, sustained TLK depletion gives rise to replication
      dependent DNA damage and p53-dependent cell cycle arrest in G1. We find that
      deficient replication-coupled de novo nucleosome assembly renders replication
      forks unstable and highly dependent on the ATR and CHK1 checkpoint kinases, as
      well as poly(adenosine 5'-diphosphate-ribose) polymerase (PARP) activity, to
      avoid collapse. Human cancer data revealed frequent up-regulation of TLK genes
      and an association with poor patient outcome in multiple types of cancer, and
      depletion of TLK activity leads to increased replication stress and DNA damage in
      a panel of cancer cells. Our results reveal a critical role for TLKs in chromatin
      replication and suppression of replication stress and identify a synergistic
      lethal relationship with checkpoint signaling and PARP that could be exploited in
      treatment of a broad range of cancers.

PMID- 30101196
TI  - High seas fisheries play a negligible role in addressing global food security.
AB  - Recent international negotiations have highlighted the need to protect marine
      diversity on the high seas-the ocean area beyond national jurisdiction. However,
      restricting fishing access on the high seas raises many concerns, including how
      such restrictions would affect food security. We analyze high seas catches and
      trade data to determine the contribution of the high seas catch to global seafood
      production, the main species caught on the high seas, and the primary markets
      where these species are sold. By volume, the total catch from the high seas
      accounts for 4.2% of annual marine capture fisheries production and 2.4% of total
      seafood production, including freshwater fisheries and aquaculture. Thirty-nine
      fish and invertebrate species account for 99.5% of the high seas targeted catch,
      but only one species, Antarctic toothfish, is caught exclusively on the high
      seas. The remaining catch, which is caught both on the high seas and in national
      jurisdictions, is made up primarily of tunas, billfishes, small pelagic fishes,
      pelagic squids, toothfish, and krill. Most high seas species are destined for
      upscale food and supplement markets in developed, food-secure countries, such as
      Japan, the European Union, and the United States, suggesting that, in aggregate,
      high seas fisheries play a negligible role in ensuring global food security.

PMID- 30101197
TI  - Development of an Electronic Documentation System for Voice Therapy: A New
      Teaching and Clinical Research Tool.
AB  - Although research on the outcomes of the treatment of voice disorders is widely
      discussed, there is a lack of information regarding the specifics of the methods
      and tasks undertaken during the therapy sessions. One reason may be a lack of a
      clear, standardized method of documentation for the voice therapy. Therefore this
      article discusses the development of a new electronic documentation system for
      voice therapy. The goals of this documentation system are to create a user
      friendly, flexible system, which implements the standard terminology and
      structure proposed in the recent voice therapy taxonomy (Van Stan, Roy, Awan,
      Stemple, & Hillman, 2015). This documentation system stores all the information
      from the therapy session in a local database, which is accessible for analysis
      within or between patients. This allows large-scale datasets to be compiled for
      future clinical research. This documentation system includes definitions for all
      terminology, and includes hierarchies, which are not required, but can be
      followed for additional structure. This documentation system can be used as a
      teaching tool, with the ability to accommodate the needs of both the novice and
      expert clinician.

PMID- 30101198
TI  - Management of Endurance Athletes with Flow Limitation in the Iliac Arteries: A
      Case Series.
AB  - Introduction: Vascular surgeons increasingly encounter flow limitation of iliac
      arteries (FLIA) in endurance athletes. An experience of managing this condition
      is reported. Report: This is a retrospective cohort analysis of prospectively
      collected data at a single vascular centre. Between 2001 and 2017, 12 athletes
      with exercise induced pain underwent investigation and assessment. Patients with
      significant radiological findings (iliac kinking +/- stenosis demonstrated on
      duplex ultrasound or catheter angiography) and dynamic flow changes (marked
      reduction in ankle brachial pressure indices following exertion, or increase in
      the common iliac artery peak systolic velocity during hip flexion on duplex)
      underwent surgery after trialling conservative management; the majority were open
      iliac shortening procedures. Patients with radiological findings, but no dynamic
      flow changes were managed conservatively. All patients were followed up.
      Discussion: There were 10 men and two women with a median age of 40 years. Nine
      patients had iliac kinking (five in isolation, four associated with stenosis),
      two had stenosis, and one had no iliac disease. Eight patients had severe
      symptoms (absolute loss of power on maximal exertion) demonstrated dynamic post
      exertional flow changes. Seven patients successfully underwent surgery, returning
      to their sport at similar intensity. One procedure was abandoned owing to severe
      adhesions from a prior procedure. This patient subsequently changed sport. Three
      patients with mild symptoms (two had reduction in power at maximal intensity, one
      was an incidental finding) and who demonstrated no clinical signs of FLIA
      continued their sport at a lower intensity. Kinking of the iliac arteries in
      athletes can occur with or without of iliac stenosis. Patients with the most
      severe iliac symptoms demonstrate dynamic post-exertional flow limitation and may
      benefit from surgery following a period of conservative management. Patients who
      have milder symptoms and no dynamic exercise flow limitations can be managed
      conservatively.

PMID- 30101195
TI  - Current evidence allows multiple models for the peopling of the Americas.
AB  - Some recent academic and popular literature implies that the problem of the
      colonization of the Americas has been largely resolved in favor of one specific
      model: a Pacific coastal migration, dependent on high marine productivity, from
      the Bering Strait to South America, thousands of years before Clovis, the
      earliest widespread cultural manifestation south of the glacial ice. Speculations
      on maritime adaptations and typological links (stemmed points) across thousands
      of kilometers have also been advanced. A review of the current genetic,
      archeological, and paleoecological evidence indicates that ancestral Native
      American population expansion occurred after 16,000 years ago, consistent with
      the archeological record, particularly with the earliest securely dated sites
      after ~15,000 years ago. These data are largely consistent with either an inland
      (ice-free corridor) or Pacific coastal routes (or both), but neither can be
      rejected at present. Systematic archeological and paleoecological investigations,
      informed by geomorphology, are required to test each hypothesis.

PMID- 30101199
TI  - Global service learning and health systems strengthening: An integrative
      literature review.
AB  - Introduction: The sustainability of many global interventions, in the absence of
      adequate local financial and human resources to sustain them in the long term, is
      questioned. In response, there has been a shift in focus among global health
      actors towards the strengthening of local health systems via global service
      learning to effectively, efficiently and sustainably deliver healthcare and build
      capacity. There has been considerable research examining the benefits of global
      service learning experiences for students, but limited research has been
      conducted to determine the impact that health sciences global service learning
      experiences are having on the host country health systems. Main text: An
      integrative review of the literature was conducted to examine the linkages
      between global service-learning and health systems strengthening. A comprehensive
      search of international literature from 2005 to 2017 in PubMed, CINAHL, Embase,
      ERIC, Scopus and Web of Science databases was conducted. The search was limited
      to peer-reviewed articles published in English language. Thematic analysis
      revealed three key themes: a dominant service-LEARNING typology, a unidirectional
      pattern from high-income to low and middle-income countries, and the preeminence
      of the nursing discipline in global service learning. There was limited evidence
      on sustainability and health systems strengthening. Conclusions: The healthcare
      workforce of the future is willing to meet the challenges facing health systems
      across the globe. Global service-learning has yet to be examined in the context
      of health systems strengthening and particularly within a context of reciprocity.
      The onus is on higher education institutions in high-income countries to develop
      and deliver evidence-based global service-learning that is beneficial and
      engaging for students while most effectively meeting the need of the global
      community.

PMID- 30101200
TI  - Assessment of psychosocial factors in office and operational groups of employees
      of a Regional Electricity Distribution Company in Iran - A case study.
AB  - Background: Many studies have shown an association between unfavorable
      psychosocial factors and personal and organizational outcomes. In recent years,
      psychosocial issues have received top priority between work environment factors.
      This study aimed to provide a first insight into psychosocial stressors in
      electricity distribution industry in Iran and compare the psychosocial factors
      between two job categories of office and operational workers. Methods: The study
      population was employees of an electricity distribution company in Iran. The
      standard Persian medium size of Copenhagen psychosocial questionnaire (COPSOQ)
      was used in this study to measure psychosocial factors. The questionnaire
      comprised 5 domains and 26 scale. Mean and standard deviation of each scale and
      domain were obtained for office and operational workers separately and the
      results were compared. Results: Higher scores were obtained in the domain of "job
      demands" of operational workers. In the domain of "job contents", More
      Unfavorable condition was obtained for office workers. No significant difference
      was seen in the domain of "inter personal relationship". More unfavorable scores
      for operational workers were obtained in the domain of work-individual interface"
      in a univariate analysis, but after adjusting the confounders including age, type
      of employment, directorship status and income, multivariate analysis did not show
      any significant difference. In the domain of "individual Health and well-being",
      higher scores were obtained for operational workers. Conclusion: This study
      provides support regarding the differences of psychosocial working environments
      between office and operational workers in electrical distribution industry. It is
      worth considering these differences of psychosocial factors at employees
      scheduling.

PMID- 30101203
TI  - Use of in-filled trenches to screen ground vibration due to impact pile driving:
      experimental and numerical study.
AB  - Vibration generated by pile driving can cause discomfort to occupants of nearby
      buildings and disturb the activities carried out in the buildings. The
      transmitted vibration will depend on both the source and the transmitting medium
      (soil), while the acceptable levels of vibration will depend on the receiver
      characteristics. Existing structures in which some sensitive processes are
      ongoing such as hospitals and laboratories can easily be affected due to the
      received vibration. Introducing a trench into the path of wave propagation has
      become one of the solutions. There is however little experimental data available
      on the effects of trenches to screen such ground borne vibration, especially that
      caused by pile driving. This paper describes a series of experiments conducted to
      investigate the characteristics of impact pile induced vibrations and the effect
      of coal bottom ash filled trenches to screen this vibration. In addition to
      experimental testing, numerical simulations are also carried out using validated
      model to examine the effects of in-fill material, impact load, soil
      characteristics and distance from the source to the trench on the vibration
      screening ability. The results of the field experiments and the numerical study
      are analysed and interpreted to provide guidelines for future research and
      design.

PMID- 30101201
TI  - Periodontal reconstruction by heparan sulfate mimetic-based matrix therapy in
      Porphyromonas gingivalis-infected mice.
AB  - Background: Periodontitis is a set of chronic inflammatory diseases affecting the
      supporting structures of the teeth, during which a persistent release of lytic
      enzymes and inflammatory mediators causes a self-perpetuating vicious cycle of
      tissue destruction and repair. A matrix-based therapy using a heparan sulfate
      (HS) analogue called ReGeneraTing Agent (RGTA) replaces destroyed HS by binding
      to available heparin-binding sites of structural molecules, leading to
      restoration of tissue homeostasis in several inflammatory tissue injuries,
      including a hamster periodontitis model. Methods: The ability of RGTA to restore
      the periodontium was tested in a model of Porphyromonas gingivalis-infected
      Balb/cByJ mice. After 12 weeks of disease induction, mice were treated weekly
      with saline or RGTA (1.5 mg/kg) for 8 weeks. Data were analyzed by
      histomorphometry. Results: RGTA treatment restored macroscopic bone loss. This
      was related to (1) a significant reduction in gingival inflammation assessed by a
      decrease in infiltrated connective tissue, particularly in cells expressing
      interleukin 1beta, an inflammatory mediator selected as a marker of inflammation;
      (2) a normalization of bone resorption parameters, i.e. number, activation and
      activity of osteoclasts, and number of preosteoclasts; (3) a powerful bone
      formation reaction. The Sharpey's fibers of the periodontal ligament recovered
      their alkaline phosphatase coating. This was obtained while P. gingivalis
      infection was maintained throughout the treatment period. Conclusions: RGTA
      treatment was able to control the chronic inflammation characteristic of
      periodontitis and blocked destruction of periodontal structures. It ensured
      tissue regeneration with recovery of the periodontium's anatomy.

PMID- 30101202
TI  - Leishmaniasis in Ethiopia: A systematic review and meta-analysis of prevalence in
      animals and humans.
AB  - Leishmaniasis is a neglected tropical disease caused by obligate intracellular
      protozoa of the genus Leishmania. Ethiopia does not have an overall estimation of
      prevalence of leishmaniasis infection at a country level. The objective of this
      systematic review and meta-analysis was to summarize and pool estimates of
      studies that report the prevalence of leishmaniasis in Ethiopia. The literature
      search was conducted to identify all published studies reporting the prevalence
      of leishmaniasis with clearly designed inclusion and exclusion criteria. From all
      screened articles, 30 studies were eligible for final meta-analysis and
      systematic review. Because substantial heterogeneity was expected, random-effects
      meta-analyses were carried out using the total sample size and number of
      positives to estimate the prevalence of the disease at a country level. Between
      study variability was high (tau2 = 0.02; heterogeneity I2 = 99.72% with
      Heterogeneity chi-square = 11985.41, a degree of freedom = 33 and P = 0.001). The
      overall random pooled prevalence of leishmaniasis was 19% (95% CI 14%-24%). Meta
      regression analysis showed that diagnosis method used have contributed to the
      heterogeneity of studies. Molecular diagnosis has significantly lower prevalence
      than microscopic examination with a coefficient of -0.32, a p-value of 0.024, and
      CI (-0.6-0.05). The result of effect estimates against its standard error showed
      there was no publication bias with a P value of 0.084. This review indicated that
      there is still a higher prevalence of Leishmaniasis in the country. Reporting on
      risk factors like sex and age affected, species of Leishmania involved and many
      more other risk factors reviewing was not possible in this study due to lack of
      completeness in articles included. However, this report is an indication that the
      country needs nationally coordinated extensive prevention and control plan to
      reduce public health and socio-economic impact of the disease.

PMID- 30101204
TI  - Prevalence, risk factors and molecular characterization of Cryptosporidium
      infection in cattle in Addis Ababa and its environs, Ethiopia.
AB  - A cross-sectional study was conducted to determine the prevalence and risk
      factors of Cryptosporidium infection and identify species of the parasite in
      cattle in central Ethiopia. Faecal samples, collected from 392 dairy cattle
      managed under intensive and extensive production system, were analyzed by the
      Modified Ziehl-Neelsen (MZN) microscopy, Nested PCR, PCR-RFLP and sequence
      analyses of the SSU rRNA gene of Cryptosporidium. The overall prevalence, the
      prevalence in the extensive and intensive farms was 18.6%, 11% and 21%,
      respectively. The infection was detected in 37.7% of the investigated farms with
      prevalence range of 7.4% -100%, and all of the six surveyed districts with
      significant (P = 0.000) prevalence difference. Restriction digestion and sequence
      analysis showed Cryptosporidium parvum and C. andersoni in 27% and 73% of the
      infections, respectively, showing an age related distribution pattern, C. parvum
      exclusively occurring in calves <2 months old and C. andersoni only in heifers
      and adult cattle. The infection was significantly associated with management
      system, farm location, herd size, source of drinking water, weaning age, presence
      of bedding, pen cleanness and cleanness of hindquarter. In conclusion,
      Cryptosporidium infection due to C. parvum and C. andersoni was prevalent in
      cattle in the study area. Cryptosporidium parvum has the concern of public health
      importance, especially to farm workers and people in close contact with cattle.
      Instigation of imperative control measure is suggested to lessen the risk of
      human infection and loss of production in dairy farms.

PMID- 30101205
TI  - Design of an experimental protocol to examine medication non-adherence among
      young drivers diagnosed with ADHD: A driving simulator study.
AB  - The diagnosis of ADHD among teens and young adults has been associated with a
      higher likelihood of motor vehicle crashes. Some studies suggest a beneficial
      effect of ADHD medication but the exact efficacy is still being debated. Further,
      medication adherence, which is low in this age group, can further reduce
      effectiveness. Our long-term objective is to reduce unsafe driving among drivers
      with ADHD by detecting medication non-adherence through driver behavior modeling
      and monitoring. As a first step, we developed the described lab study protocol to
      obtain reliable driver behavior data that will then be used to design and train
      behavior models built through machine learning. This experimental study protocol
      was developed to systematically compare driving behaviors under two medication
      conditions (before and after intake of medication) among young adults with ADHD
      and a control group of non-ADHD. A driving simulator was used to examine driving
      behaviors and interactions with traffic. The primary outcome was speed management
      for two comparisons (ADHD vs. non-ADHD and before vs. after medication), and
      secondary objectives involved understanding differences among the participants
      utilizing self-reported surveys about ADHD symptoms, drivers' knowledge, and
      perception about safety. The study protocol was designed to maximize participant
      safety and efficiency of data collection, as multiple measures were collected
      over two 2-h study visits. The sampled ADHD drivers were demographically and
      psychosocially similar but clinically different from the non-ADHD group. Overall,
      this protocol was effective in participant recruitment and retention, allowed
      staggered data collection, and can be incorporated in a subsequent clinical trial
      that examines the efficacy of a machine-learning based driver monitoring
      intervention.

PMID- 30101206
TI  - Simple limbal epithelial transplantation for recurrent pterygium: A case series.
AB  - Purpose: Pterygium recurrence is a common complication of pterygium removal.
      Multiple surgical and medical approaches have been utilized to reduce recurrence
      rates. The present case series proposes a novel way to treat recurrent pterygia,
      by using the simple limbal epithelial transplantation (SLET) technique.
      Observations: The cases of four patients who presented with recurrent pterygium
      were reviewed. In all four of the cases reported, the SLET procedure went without
      complication. There were no significant recurrences at each of the patient's most
      recent follow-up visits. Conclusions and importance: This is the first report of
      SLET being used as a treatment modality for recurrent pterygium. Further studies
      are required to more reliably demonstrate the utility of the procedure in this
      clinical circumstance, but our results are encouraging that in select patients,
      this may be a viable option in treating aggressive recurrent pterygia.

PMID- 30101207
TI  - Goniosynechialysis for secondary angle closure glaucoma in aphakic patient after
      pars plana vitrectomy.
AB  - Purpose: To report the effectiveness of Goniosynechialysis (GSL) treating
      elevated intraocular pressure (IOP) in an aphakic eye with peripheral anterior
      synechiae (PAS) formation after vitrectomy. Observations: A 39-year-old gentleman
      with history of lamellar keratoplasty for corneal ectasia and blunt trauma to the
      right eye necessitating vitrectomy and lensectomy presented to our glaucoma unit
      with a secondary angle closure and an IOP of 50 mmHg. This was successfully
      treated with GSL and one year after surgery, the patient maintains a normal IOP
      without the use of medication. Conclusions and importance: GSL may successfully
      restore angle integrity in aphakic patients following vitreoretinal surgery and
      avoid the need for a glaucoma drainage device.

PMID- 30101209
TI  - Keratoconus: In Vitro and In Vivo.

PMID- 30101211
TI  - The anatomy of job polarisation in the UK.
AB  - This paper studies the contribution of different skill groups to the polarisation
      of the UK labour market. We show that the large increase in graduate numbers
      contributed to the substantial reallocation of employment from middling to top
      occupations which is the main feature of the polarisation process in the UK over
      the past three decades. The increase in the number of immigrants, on the other
      hand, does not account for any particular aspect of the polarisation in the UK.
      Changes in the skill mix of the workforce account for most of the decline in
      routine employment across the occupational distribution, but within-group changes
      account for most of the decline in routine occupations in middling occupations.
      In addition, there is no clear indication of polarisation within all skill groups
      a fact that previous literature has cited as evidence that technology drives the
      decline of middling occupations. These findings differ substantially from
      previous evidence on the US and cast doubts on the role of technology as the main
      driver of polarisation in the UK.

PMID- 30101210
TI  - Role of Vitamin A in Modulating Graft-versus-Host Disease.
AB  - Vitamin A is an essential micronutrient that participates in a wide range of
      biological processes. Retinoic acid (RA) is an active metabolite of vitamin A
      that functions as an immune regulator. Graft-versus-host disease (GVHD) is a
      major complication of allogeneic hematopoietic stem cell transplantation (HSCT).
      It is characterized by extensive inflammation arising from an alloimmune response
      involving various host and donor immune cells. Since vitamin A affects different
      immune cell lineages and regulates an array of immune responses, vitamin A, and
      more specifically retinoic acid, is likely to influence the incidence and/or
      severity of GVHD. Indeed, recent preclinical and clinical data support this
      concept. In this review, we briefly summarize recent advances in our
      understanding of the potential role of vitamin A in modulating GVHD risk after
      allogeneic HSCT.

PMID- 30101208
TI  - Effect of Source Animal Age upon Macrophage Response to Extracellular Matrix
      Biomaterials.
AB  - Extracellular matrix biomaterials have been shown to promote constructive
      remodeling in many preclinical and clinical applications. This response has been
      associated with the promotion of a timely switch from pro-inflammatory (M1) to
      anti-inflammatory (M2) macrophages. A previous study has shown that this
      beneficial response is lost when these biomaterials are derived from aged
      animals. This study examined the impact of small intestine submucosa (SIS)
      derived from 12, 26 and 52 week old pigs on the phenotype and function of bone
      marrow macrophages derived either from 2 or 18 month old mice. Results showed
      that 52 week old SIS promoted less iNOS in 2 month macrophages and Fizz1
      expression in 2 and 18 month compared to 12 week SIS. Pro-inflammatory cytokine
      exposure to 52 week SIS-treated macrophages resulted in higher iNOS in 18 month
      macrophages and reduced MHC-II expression in 2 month macrophages, as well as
      reduced nitric oxide production in comparison to 12 week SIS. These results
      indicate that ECM derived from aged animals promotes an altered macrophage
      phenotype compared to young controls. This suggests that sourcing of ECM from
      young donors is important to preserve constructive remodeling outcomes of ECM
      biomaterials. Alteration of macrophage phenotype by aged ECM also raises the
      hypothesis that alterations in aged ECM may play a role in immune dysfunction in
      aged individuals.

PMID- 30101212
TI  - Making Contact: VAP Targeting by Intracellular Pathogens.
AB  - In naive cells, the endoplasmic reticulum (ER) and the ER-resident VAP proteins
      are common components of sites of membrane contacts that mediate the non
      vesicular transfer of lipids between organelles. There is increasing recognition
      that the hijacking of VAP by intracellular pathogens is a novel mechanism of host
      pathogen interaction. Here, we summarize our recent findings showing that the
      Chlamydia inclusion membrane protein IncV tethers the ER to the inclusion
      membrane by binding to VAP via the molecular mimicry of two eukaryotic FFAT
      motifs. We extend the discussion to other microorganisms that have evolved
      similar mechanisms.

PMID- 30101213
TI  - In Close Proximity: The Lipid Droplet Proteome and Crosstalk With the Endoplasmic
      Reticulum.
AB  - Lipid droplets (LDs) are conserved, endoplasmic reticulum (ER)-derived organelles
      that act as a dynamic cellular repository for neutral lipids. Numerous studies
      have examined the composition of LD proteomes by using mass spectrometry to
      identify proteins present in biochemically isolated buoyant fractions that are
      enriched in LDs. Although many bona fide LD proteins were identified, high levels
      of non-LD proteins that contaminate buoyant fractions complicate the detection of
      true LD proteins. To overcome this problem, we recently developed a proximity
      labeling proteomic method to define high-confidence LD proteomes. Moreover,
      employing this approach, we discovered that ER-associated degradation impacts the
      composition of LD proteomes by targeting select LD proteins for clearance by the
      26S proteasome as they transit between the ER and LDs. These findings implicate
      the ER as a site of LD protein degradation and underscore the high degree of
      crosstalk between ER and LDs.

PMID- 30101215
TI  - MicroRNA-146a & hematopoiesis: friend or foe in atherosclerosis.

PMID- 30101214
TI  - Inaugural Editorial: Searching for Magic Bullets.
AB  - Single domain antibodies have emerged as a new class of therapeutic molecules in
      antibody engineering. A single domain antibody (shark VNAR), in contrast to a
      conventional antibody (Fv), is capable of binding a buried functional site
      consisting of the enzyme's substrate binding pocket. For additional information,
      see Ho, Searching for magic bullets, Antibody Therapeutics. Volume 1, Issue 1, 20
      June 2018, Pages 1-5. DOI: https://doi.org/10.1093/abt/tby001.

PMID- 30101216
TI  - A review of cancer outcomes among persons dually enrolled in Medicare and
      Medicaid.
AB  - The fragmentation and lack of coordination of health care may result in less
      efficient and more costly care and lead to poorer outcomes. There has been
      increasing interest in examining cancer outcomes among persons who are dually
      enrolled in Medicare and Medicaid. Previous studies have identified disparities
      in the quality of cancer treatment according to race, ethnicity, socioeconomic
      status, and source of health insurance. This article, which is based upon
      bibliographic searches in PubMed, reviews the literature on dual enrollment in
      Medicare and Medicaid and cancer survival and quality of cancer treatment. A
      total of 65 articles were identified. Of the 65 articles that were screened using
      the full texts or abstracts, 13 studies met the eligibility criteria, one cross
      sectional study and 12 cohort studies. The results of this systematic review
      indicate that there is only limited evidence that dual enrollment in Medicare and
      Medicaid is associated with poorer survival or quality of cancer care. The number
      of studies that have looked for associations between dual Medicare-Medicaid
      status and survival and quality of cancer treatment is still small. Outcomes and
      cancer site(s) varied among the studies. Additional studies are needed to
      determine the replicability of findings reported to date. Of particular interest
      are studies of major forms of cancer (breast, prostate, lung, colorectal) that
      include adequate numbers of patients described by insurance status, race,
      comorbidity, stage, receipt of appropriate cancer therapy, and survival.

PMID- 30101217
TI  - Modular Protein Engineering Approach to the Functionalization of Gold
      Nanoparticles for Use in Clinical Diagnostics.
AB  - Functional protein-gold nanoparticle (AuNP) conjugates have a wide variety of
      applications including biosensing and drug delivery. Correct protein orientation,
      which is important to maintain functionality on the nanoparticle surface, can be
      difficult to achieve in practice, and dedicated protein scaffolds have been used
      on planar gold surfaces to drive the self-assembly of oriented protein arrays.
      Here we use the transmembrane domain of Escherichia coli outer membrane protein A
      (OmpATM) to create protein-AuNP conjugates. The addition of a single cysteine
      residue into a periplasmic loop, to create cysOmpATM, drives oriented assembly
      and increased equilibrium binding. As the protein surface concentration
      increases, the sulfur-gold bond in cysOmpATM creates a more densely populated
      AuNP surface than the poorly organized wtOmpATM layer. The functionalization of
      AuNP improved both their stability and homogeneity. This was further exploited
      using multidomain protein chimeras, based on cysOmpATM, which were shown to form
      ordered protein arrays with their functional domains displayed away from the AuNP
      surface. A fusion with protein G was shown to specifically bind antibodies via
      their Fc region. Next, an in vitro selected single chain antibody (scFv)
      cysOmpATM fusion protein, bound to AuNP, detected influenza A nucleoprotein, a
      widely used antigen in diagnostic assays. Finally, using the same scFv-cysOmpATM
      AuNP conjugates, a prototype lateral flow assay for influenza demonstrated the
      utility of fully recombinant self-assembling sensor layers. By simultaneously
      removing the need for both animal antibodies and a separate immobilization
      procedure, this technology could greatly simplify the development of a range of
      in vitro diagnostics.

PMID- 30101219
TI  - Anxiety and depression in spasmodic dysphonia patients.
AB  - Objective/Hypothesis: Experts used to believe that spasmodic dysphonia (SD) was a
      psychogenic disorder. Although SD is now established as a neurological disorder,
      the rates of co-morbid anxiety and depression range from 7.1% to 62%. Our
      objective was to study the prevalence and risk factors associated with these mood
      disorders in SD patients. Study design: Retrospective. Methods: SD patients who
      presented for botulinum toxin injections were recruited. Demographic data,
      Hospital Anxiety and Depression Scale (HADS), Voice Handicap Index-10 (VHI-10),
      General Self-Efficacy scale (GSES), Disease Specific Self-Efficacy in Spasmodic
      Dysphonia scale (DSSE), and Consensus Auditory Perceptual Evaluation of Voice
      (CAPE-V) were collected. Results: One hundred and forty two patients (age (59.2
      +/- 13.6) years, 25.4% male) had VHI-10 of 26.3 +/- 6.9 (mean +/- standard
      deviation), GSES 33.2 +/- 5.8, CAPE-V 43.9 +/- 20.9, HADS anxiety 6.7 +/- 3.7,
      and HADS depression 3.6 +/- 2.8. About 19 (13.4%) and 4 (2.8%) had symptoms of
      anxiety and depression respectively. Final linear regression model for HADS
      anxiety (R2 = 32.90%) showed that patients who were less likely to have anxiety
      symptoms were older age (p < 0.001), male (p = 0.002), have higher GSES (p <
      0.001) and lower VHI-10 (p = 0.004). Final linear regression model for HADS
      depression score (R2 = 34.42%) showed that patients who were less likely to have
      depressive symptoms had high DSSES (p < 0.001). Conclusions: Prevalence of
      anxiety (13.4%) and depression (2.8%) in SD were lower than previously reported
      in the literature. Risk factors for anxiety were: younger age, female gender,
      lower general self-efficacy, and higher perceived vocal handicap. The main risk
      factor for depression was lower disease specific self-efficacy.

PMID- 30101218
TI  - Immunohistochemistry of the circadian clock in mouse and human vascular tissues.
AB  - Aim: The circadian clock is a molecular network that controls the body
      physiological rhythms. In blood vessels, the circadian clock components modulate
      vascular remodeling, blood pressure, and signaling. The goal in this study was to
      determine the pattern of expression of circadian clock proteins in the
      endothelium, smooth muscle, and adventitia of the vasculature of human and mouse
      tissues. Methods: Immunohistochemistry was performed in frozen sections of mouse
      aorta, common carotid artery, femoral artery, lung, and heart at 12 AM and 12 PM
      for Bmal1, Clock, Npas2, Per and other clock components. Studies of expression
      were also assessed in human saphenous vein both by immunoblotting and
      immunohistochemistry. Results: In this study, we identified the expression of
      Bmal1, Clock, Npas, Per1, Cry1, and accessory clock components by
      immunohistochemical staining in the endothelium, smooth muscle and adventitia of
      the mouse vasculature with differing temporal and cellular profiles depending on
      vasculature and tissue analyzed. The human saphenous vein also exhibited
      expression of clock genes that exhibited an oscillatory pattern in Bmal1 and Cry
      by immunoblotting. Conclusion: These studies show that circadian clock components
      display differences in expression and localization throughout the cardiovascular
      system, which may confer nuances of circadian clock signaling in a cell-specific
      manner.

PMID- 30101220
TI  - Laryngotracheal stenosis in burn patients requiring mechanical ventilation.
AB  - Objective: To identify the incidence of laryngotracheal stenosis (LTS) in burn
      patients requiring mechanical ventilation at a regional academic burn center.
      Methods: A retrospective review of all burn patients requiring endotracheal
      intubation or tracheostomy for airway management between 2003 and 2009 was
      performed. A group of trauma patients requiring similar airway instrumentation
      during the same period of time was used as a control. Results: None of the trauma
      patients and 2 of the burn patients developed LTS. Both presented with stridor
      and were diagnosed within 2-5 weeks after extubation. One patient underwent
      successful carbon dioxide laser radial incision and dilation and continues to do
      well. The other patient failed endoscopic treatment and required T-tube
      placement. The incidence of LTS in burn patients requiring mechanical ventilation
      was 2.98% overall and 4.76% among those with inhalational injury. Conclusions:
      Patients become symptomatic within weeks of the initial injury. Treatment is
      challenging and multiple surgical procedures are often required. A larger study
      is necessary to determine if the incidence is higher among burn patients.

PMID- 30101221
TI  - Difficult airway management in children and young adults with arthrogryposis.
AB  - Objective: To review current evidence and experience with anesthesia and airway
      management issues in children and young adults with arthrogryposis. Data sources:
      Review of existing world literature and description of personal experience at a
      center for children's orthopedic surgery and rehabilitation over 2 decades.
      Methods: Description of common problems and their solutions in this unusual and
      diverse group of patients. Results: Arthrogryposis multiplex congenital includes
      more than 400 conditions that lead to congenital joint contractures affecting
      more than one body area. Among the many causes of arthrogryposis, 50%-65% fall
      into two large categories - amyoplasia and distal arthrogryposis. There is
      general agreement that best function in children with arthrogryposis is achieved
      through early mobilization of joint contractures. Children with arthrogryposis
      average >5 operative procedures during childhood. Anesthesia for these procedures
      may be complicated by limited jaw mobility and mouth opening, restricted lung
      development, positioning difficulties, difficult venous access and concerns about
      increased risk for malignant hyperthermia. 75% of arthrogryposis patients do not
      have a difficult airway. For those with a history of airway problems or those
      meeting criteria for a difficult airway, careful advanced planning helps to
      assure safe and successful surgery. We describe several specialized techniques
      for endotracheal intubation of children with arthrogryposis. Conclusions:
      Children and young adults with arthrogryposis are a diverse group. Many pose
      unique challenges for airway and surgical management. Review of individual
      anesthesia records and careful advanced planning by a coordinated, experienced
      airway team can lead to best outcomes from arthrogryposis surgery.

PMID- 30101222
TI  - Injection medialization laryngoplasty improves dysphagia in patients with
      unilateral vocal fold immobility.
AB  - Objective: To assess patient reported swallowing outcomes before and after
      injection medialization laryngoplasty in patients with unilateral vocal fold
      immobility (UVFI). Methods: Case series with chart review of patients with UVFI
      who underwent injection medialization laryngoplasty at a community laryngology
      practice by a single clinician between October 2015 and December 2017. Patient
      reported validated surveys of swallowing impairment, Eating Assessment Tool (EAT
      10), demographics, etiology and duration of symptoms were recorded before and
      after injection. A paired t test was done on EAT-10 surveys before and after IML
      to assess for statistical significance. Results: Twenty-one patients with UVFI
      and glottic insufficiency underwent IML between October 2015 and December 2017.
      Nineteen of 21 patients (90%) presented with dysphagia (EAT-10 >= 3). 76% of
      patients with dysphagia reported improvement in swallowing function after IML.
      The EAT-10 scores of UVFI patients with dysphagia before and after IML were 17.0
      +/- 14.0 and 4.2 +/- 9.6, respectively (p = 0.004). Conclusions: Nearly all
      patients with UVFI and glottic insufficiency report associated dysphagia. Three
      fourths of these patients perceive improvement in their swallowing function after
      injection medialization laryngoplasty. Patients with idiopathic UVFI may have a
      more sustained improvement and those with severe preop dysphagia may not benefit.
      Further research is necessary to refine patient selection and to assess duration
      of improved swallowing function.

PMID- 30101223
TI  - Voice outcome measures after flexible endoscopic injection laryngoplasty.
AB  - Objective: To report voice outcome measures after injection laryngoplasty using
      the transnasal or transoral flexible endoscopic technique. Methods: A
      retrospective review of all patients who underwent flexible endoscopic injection
      laryngoplasty between June 2010 and August 2016 was carried out. Only those
      patients who had pre- and post-injection voice outcome measures recorded were
      included. Voice outcome measures recorded included perceptual voice evaluation
      using GRBAS, Voice Handicap Index-10 (VHI-10), maximum phonation time (MPT) and
      closed quotient (CQ) before and after treatment. Results: Forty-six patients were
      identified, of which 32 had pre- and post-injection voice outcome measures
      recorded. There were 19 males and 13 females. The mean age was 56.97 years (range
      20-86 years) and the most common indication was unilateral vocal fold paralysis.
      Thirteen patients had a transnasal flexible endoscopic injection), while 19
      patients were injected transorally. Following injection laryngoplasty, there was
      significant improvement in the mean grade of dysphonia (2.81 vs. 1.22, P < 0.01,
      roughness (2.44 vs. 1.34, P < 0.01), breathiness (2.72 vs. 1.13, P < 0.01),
      asthenia (2.78 vs. 1.06, P < 0.01), and strain (2.44 vs. 1.19, P < 0.01), MPT
      (3.85 s vs. 9.85 s, P < 0.01) and mean CQ (0.19 vs. 0.46, P < 0.01). There was
      also a decrease in the mean VHI-10 score (33.31 vs. 7.94, P < 0.01). Conclusion:
      s: Patients achieved significant improvement in both subjective and objective
      voice measures after flexible endoscopic injection laryngoplasty via the nasal or
      transoral route. Voice outcomes were comparable to those reported for other
      approaches. This technique provides an alternative approach for the management of
      patients with vocal fold paralysis or glottal insufficiency.

PMID- 30101224
TI  - Diagnostic utility of flexible fiberoptic nasopharyngolaryngoscopy recorded onto
      a smartphone: A pilot study.
AB  - Objectives: To evaluate the diagnostic accuracy of flexible fiberoptic
      examinations of the larynx recorded onto smartphones. Methods: Prospective,
      blinded study of inpatients requiring laryngoscopy. A live exam was performed,
      then a smartphone was attached to the endoscope using a novel coupling device and
      the same examination was recorded. The live and recorded exams were evaluated by
      two laryngologists, each blinded to the findings of the other. Results: Eighteen
      subjects were evaluated. Evaluation of airway patency was identical (Kappa = 1.0
      [1, 1]). Evaluation of vocal cord motion was identical for 14 subjects: 9 normal,
      3 paretic, 2 paralytic (Kappa = 0.69 [0.38, 1]). Conclusion: There is high
      correlation between laryngeal diagnoses using live flexible fiberoptic
      laryngoscopy and recordings using a coupling device to transfer the recordings on
      to smartphones. Critical findings such as airway patency and vocal fold motion
      showed the highest correlation.

PMID- 30101225
TI  - Ex vivo ovine model for teaching open laryngotracheal surgery.
AB  - Objective: To develop an animal model for teaching open laryngotracheal surgical
      procedures. Methods: The heads and necks from 5 pre-pubescent sheep were
      harvested after humane anesthesia. After 2-5 days to allow for rigor mortis to
      resolve, a specimen was supported with sandbags on an operating table. Operative
      procedures including tracheotomy, medialization laryngoplasty, anterior cartilage
      grafting, tracheal resection with primary anastomosis, and laryngectomy with
      closure of the pharynx were attempted. Results: The ovine head and neck provided
      an accurate model for simulation of all attempted procedures. Ovine tissue
      resembled that of humans in mechanical properties and handling. Postsurgical
      endoscopy confirmed graft alignment. Conclusions: The sheep head and neck
      provides an inexpensive, realistic, and safe model for surgical training for a
      variety of open laryngotracheal procedures. This is particularly relevant given
      the recent emphasis on surgical simulation and the relative rarity of some of
      these procedures in residency training.

PMID- 30101226
TI  - Taste acceptability of thickening agents.
AB  - Objective: Patients with dysphagia are often unable to manage secretions and
      liquids, necessitating the use of commercial thickeners to decrease the
      likelihood of aspiration. This study aims to evaluate the effect of commercially
      available thickeners on hedonic perception of various liquids. Methods: Forty
      subjects without preexisting dysphagia or anosmia were recruited from a tertiary
      care otorhinolaryngology clinic over a five-month period. Participants were
      presented with samples of three unthickened liquids (ice water, chilled ginger
      ale, and hot coffee) and their thickened counterparts and asked to rate the taste
      acceptability of the liquids on an 11-point visual analog scale. The study was
      reviewed by the hospital's Institutional Review Board and determined to be IRB
      exempt. Results: A statistically significant preference for unthickened liquids
      over their thickened counterpart was observed across flavors (P < 0.0001). Of the
      thickened liquid samples, study participants expressed the strongest preference
      for thickened ginger ale. Conclusion: Thickened liquids are perceived as
      significantly less palatable than their unthickened counterparts, although ginger
      ale may be better tolerated when thickened than coffee or water. Providers should
      be aware of the impact of thickeners on taste acceptability when counseling
      patients with dysphagia.

PMID- 30101227
TI  - Usefulness of supraclavicular flap in reconstruction following resection of oral
      cancer.
AB  - Objective: To evaluate the usefulness of supraclavicular artery flap in
      reconstruction of defects following resection of buccal mucosa cancer. Methods:
      Twenty-five patients who presented to R.L Jalappa Hospital and Research centre
      and diagnosed as squamous cell carcinoma of buccal mucosa staged T2 and above
      were included in our study. All patients underwent wide excision of tumour and
      neck dissection. Six patients underwent hemi-mandibulectomy while 4 patients
      underwent marginal mandibulectomy depending on extent of the tumour along with
      neck dissection. The defect following surgery was reconstructed using the
      supraclavicular artery flap and were followed up for minimum 6 months during
      which they were assessed for the functional and aesthetic outcome using a scoring
      system. The details of the scoring system comprised of 7 attributes. Each
      attribute was given a score of 10 if the patients experienced that attribute,
      while a score of 0 was given if the patient did not experience that particular
      attribute. Results: Seven (28%) patients had complete necrosis of the flap. One
      patient had a local recurrence 2 months following surgery and was lost to follow
      up. The remaining 17 patients were followed up for a minimum of 6 months and a
      scoring system was adopted to evaluate the functional and aesthetic outcome of
      the supraclavicular flap. We observed that 14 patients had an excellent outcome
      score (58%), 3 patients had a good outcome score (13%), while 7 patients (28%)
      had flap necrosis. Conclusions: We find the supraclavicular flap to be safe,
      technically simple, sensate, thin, pliable and reliable regional fasciocutaneous
      flap in reconstructing intra oral defects. Preserving the external jugular vein
      and sacrificing supraclavicular nerves give good outcome.

PMID- 30101228
TI  - Food Insecurity among Households with and without Podoconiosis in East and West
      Gojjam, Ethiopia.
AB  - Background: Household food insecurity remained one of the most crucial challenges
      to economic development and has been aggravated by household health conditions.
      Nearly one billion people are undernourished of which 98% in developing countries
      like Ethiopia. Objective: To assess households' food insecurity among
      podoconiosis patients and non-podoconiosis in East and West Gojjam Zone,
      Ethiopia, 2016. Method: A community based comparative cross sectional study was
      conducted in East and West Gojjam, 2016. Multi-stage sampling technique was
      employed to select 208 podoconiosis and 400 non-podoconiosis household heads.
      Data was collected by using structured and pretested questionnaires. The
      collected data was cleaned, coded and entered into Epi data then exported to SPSS
      version 22. Descriptive and inferential statistics was performed. Both bivariate
      and multivariate logistic regression analyses was employed. The association was
      measured by adjusted odds ratio (AOR), 95%CI (confidence interval) and P < 0.05
      was considered statistically significant. Result: A total of 608 study
      participants were involved in this study. Food insecurity podoconiosis patients
      and non-podoconiosis household was 83.7%, 53% respectively (p = 0.0001).
      Podoconiosis and non- podoconiosis whose heads could not read and write AOR =
      5.84, (95% CI: 2.14, 15.95) and AOR = 1.70, (95% CI: 1.06, 2.72) were food
      insecure respectively. Podoconiosis patients without off farm activities AOR =
      4.90, (95% CI: 1.60, 14.95), not using fertilizer AOR = 4.38, (95% CI: 1.15,
      16.67) and living at > 5 kilo meter distance from market AOR = 4.47, (95% CI:
      1.38, 14.48) were food insecure. Non-podoconiosis heads with no perennial plant
      AOR = 2.11, (95% CI: 1.17, 3.34), not using improved seeds AOR = 2.20, (95% CI:
      1.25, 3.87), no access to asset building program AOR = 2.07, (95% CI: 1.27,
      3.34), living in medium and low altitude AOR = 8.87, (95% CI: 1.81, 43.40) and
      AOR = 10.04, (95% CI: 1.90, 52.93) were food insecure. Conclusion: Food
      insecurity was higher among podoconiosis than non-podoconiosis households. Being
      a female, unable to read and write absence of off farm activities, not using of
      fertilizers and living in more distance from market were significantly associated
      with food insecurity among podoconiosis patients. Special emphasis should be
      given for improvement of food security of podoconiosis and non-podoconiosis
      households.

PMID- 30101229
TI  - Novel Single and Multiple Shell Uniform Sampling Schemes for Diffusion MRI Using
      Spherical Codes.
AB  - A good data sampling scheme is important for diffusion MRI acquisition and
      reconstruction. Diffusion Weighted Imaging (DWI) data is normally acquired on
      single or multiple shells in q-space. The samples in different shells are
      typically distributed uniformly, because they should be invariant to the
      orientation of structures within tissue, or the laboratory coordinate frame. The
      Electrostatic Energy Minimization (EEM) method, originally proposed for single
      shell sampling scheme in dMRI by Jones et al., was recently generalized to the
      multi-shell case, called generalized EEM (GEEM). GEEM has been successfully used
      in the Human Connectome Project (HCP). Recently, the Spherical Code (SC) concept
      was proposed to maximize the minimal angle between different samples in single or
      multiple shells, producing a larger angular separation and better rotational
      invariance than the GEEM method. In this paper, we propose two novel algorithms
      based on the SC concept: 1) an efficient incremental constructive method, called
      Iterative Maximum Overlap Construction (IMOC), to generate a sampling scheme on a
      discretized sphere; 2) a constrained non-linear optimization (CNLO) method to
      update a given initial scheme on the continuous sphere. Compared to existing
      incremental estimation methods, IMOC obtains schemes with much larger separation
      angles between samples, which are very close to the best known solutions in
      single shell case. Compared to the existing Riemannian gradient descent method,
      CNLO is more robust and stable. Experiments demonstrated that the two proposed
      methods provide larger separation angles and better rotational invariance than
      the state-of-the-art GEEM and methods based on the SC concept.

PMID- 30101230
TI  - Diffusion Compartmentalization Using Response Function Groups with Cardinality
      Penalization.
AB  - Spherical deconvolution (SD) of the white matter (WM) diffusion-attenuated signal
      with a fiber signal response function has been shown to yield high-quality
      estimates of fiber orientation distribution functions (FODFs). However, an
      inherent limitation of this approach is that the response function (RF) is often
      fixed and assumed to be spatially invariant. This has been reported to result in
      spurious FODF peaks as the discrepancy of the RF with the data increases. In this
      paper, we propose to utilize response function groups (RFGs) for robust
      compartmentalization of diffusion signal and hence improving FODF estimation.
      Unlike the aforementioned single fixed RF, each RFG consists of a set of RFs that
      are intentionally varied to capture potential signal variations associated with a
      fiber bundle. Additional isotropic RFGs are included to account for signal
      contributions from gray matter (GM) and cerebrospinal fluid (CSF). To estimate
      the WM FODF and the volume fractions of GM and CSF compartments, the RFGs are
      fitted to the data in the least-squares sense, penalized by the cardinality of
      the support of the solution to encourage group sparsity. The volume fractions
      associated with each compartment are then computed by summing up the volume
      fractions of the RFs within each RFGs. Experimental results confirm that our
      method yields estimates of FODFs and volume fractions of diffusion compartments
      with improved robustness and accuracy.

PMID- 30101231
TI  - Iterative Subspace Screening for Rapid Sparse Estimation of Brain Tissue
      Microstructural Properties.
AB  - Diffusion magnetic resonance imaging (DMRI) is a powerful imaging modality due to
      its unique ability to extract microstructural information by utilizing restricted
      diffusion to probe compartments that are much smaller than the voxel size. Quite
      commonly, a mixture of models is fitted to the data to infer microstructural
      properties based on the estimated parameters. The fitting process is often non
      linear and computationally very intensive. Recent work by Daducci et al. has
      shown that speed improvement of several orders of magnitude can be achieved by
      linearizing and recasting the fitting problem as a linear system, involving the
      estimation of the volume fractions associated with a set of diffusion basis
      functions that span the signal space. However, to ensure coverage of the signal
      space, sufficiently dense sampling of the parameter space is needed. This can be
      problematic because the number of basis functions increases exponentially with
      the number of parameters, causing computational intractability. We propose in
      this paper a method called iterative subspace screening (ISS) for tackling this
      ultrahigh dimensional problem. ISS requires only solving the problem in a medium
      size subspace with a dimension that is much smaller than the original space
      spanned by all diffusion basis functions but is larger than the expected
      cardinality of the support of the solution. The solution obtained for this
      subspace is used to screen the basis functions to identify a new subspace that is
      pertinent to the target problem. These steps are performed iteratively to seek
      both the solution subspace and the solution itself. We apply ISS to the
      estimation of the fiber orientation distribution function (ODF) and demonstrate
      that it improves estimation robustness and accuracy.

PMID- 30101232
TI  - Hierarchical Reconstruction of 7T-like Images from 3T MRI Using Multi-level CCA
      and Group Sparsity.
AB  - Advancements in 7T MR imaging bring higher spatial resolution and clearer tissue
      contrast, in comparison to the conventional 3T and 1.5T MR scanners. However, 7T
      MRI scanners are less accessible at the current stage due to higher costs.
      Through analyzing the appearances of 7T images, we could improve both the
      resolution and quality of 3T images by properly mapping them to 7T-like images;
      thus, promoting more accurate post-processing tasks, such as segmentation. To
      achieve this method based on an unique dataset acquired both 3T and 7T images
      from same subjects, we propose novel multi-level Canonical Correlation Analysis
      (CCA) method and group sparsity as a hierarchical framework to reconstruct 7T
      like MRI from 3T MRI. First, the input 3T MR image is partitioned into a set of
      overlapping patches. For each patch, the local coupled 3T and 7T dictionaries are
      constructed by extracting the patches from a neighboring region from all aligned
      3T and 7T images in the training set. In the training phase, we have both 3T and
      7T MR images scanned from each training subject. Then, these two patch sets are
      mapped to the same space using multi-level CCA. Next, each input 3T MRI patch is
      sparsely represented by the 3T dictionary and then the obtained sparse
      coefficients are utilized to reconstruct the 7T patch with the corresponding 7T
      dictionary. Group sparsity is further utilized to maintain the consistency
      between neighboring patches. Such reconstruction is performed hierarchically with
      adaptive patch size. The experiments were performed on 10 subjects who had both
      3T and 7T MR images. Experimental results demonstrate that our proposed method is
      capable of recovering rich structural details and outperforms other methods,
      including the sparse representation method and CCA method.

PMID- 30101233
TI  - Semi-supervised Hierarchical Multimodal Feature and Sample Selection for
      Alzheimer's Disease Diagnosis.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disease that impairs
      a patient's memory and other important mental functions. In this paper, we
      leverage the mutually informative and complementary features from both structural
      magnetic resonance imaging (MRI) and single nucleotide polymorphism (SNP) for
      improving the diagnosis. Due to the feature redundancy and sample outliers,
      direct use of all training data may lead to suboptimal performance in
      classification. In addition, as redundant features are involved, the most
      discriminative feature subset may not be identified in a single step, as commonly
      done in most existing feature selection approaches. Therefore, we formulate a
      hierarchical multimodal feature and sample selection framework to gradually
      select informative features and discard ambiguous samples in multiple steps. To
      positively guide the data manifold preservation, we utilize both labeled and
      unlabeled data in the learning process, making our method semi-supervised. The
      finally selected features and samples are then used to train support vector
      machine (SVM) based classification models. Our method is evaluated on 702
      subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and
      the superior classification results in AD related diagnosis demonstrate the
      effectiveness of our approach as compared to other methods.

PMID- 30101234
TI  - Two dimensional monolayer rhombic silicene on the diamond (111) surface.
AB  - Two-dimensional rhombic silicene (named r-silicene) bonded on the diamond (111)
      surface with a (1 * 1) configuration is predicted by density functional theory.
      The planar structure of r-silicene has P6/mmm symmetry, and it is dynamically and
      thermodynamically stable on the diamond surface. r-Silicene has a metallic
      character, which is different to both bulk cubic Si and hexagonal silicene. The
      hybrid structure of r-silicene/diamond consists of a metallic surface and a wide
      band gap semiconductor diamond substrate, providing a novel low-dimensional
      composite based on silicon-diamond to realize high performance nanodevices.
      Moreover, a similar rhombic configuration of monolayer germanene has been
      theoretically constructed on the diamond (111) substrate.

PMID- 30101235
TI  - The environmental stability of large-size and single-crystalline antimony flakes
      grown by chemical vapor deposition on SiO2 substrates.
AB  - The environmental stability of large-sized and single-crystalline antimony flakes
      was systematically investigated with temperature and time dependence at fixed
      humidity. The antimony flakes used in this work were grown by chemical vapor
      deposition (CVD) directly on SiO2 substrates, where antimonene layers were
      stacked to a few tens of nm thickness with a typical area of ~40 MUm.

PMID- 30101236
TI  - Compositional inhomogeneity and tuneable thermal expansion in mixed-metal ZIF-8
      analogues.
AB  - We study the structural and thermomechanical effects of cation substitution in
      the compositional family of metal-organic frameworks Zn1-xCdx(mIm)2 (HmIm = 2
      methylimidazole). We find complete miscibility for all compositions x, with
      evidence of inhomogeneous distributions of Cd and Zn that in turn affect
      framework aperture characteristics. Using variable-temperature X-ray powder
      diffraction measurements, we show that Cd substitution drives a threefold
      reduction in the magnitude of thermal expansion behaviour. We interpret this
      effect in terms of an increased density of negative thermal expansion modes in
      the more flexible Cd-rich frameworks.

PMID- 30101237
TI  - Photo-induced direct interfacial charge transfer at TiO2 modified with
      hexacyanoferrate(iii).
AB  - Photo-induced electron-transfer reactions occurring at the interface between
      titanium dioxide modified with hexacyanoferrate(iii) (Fe(iii)-CN-TiO2) were
      characterized. After the modification of TiO2 with [Fe(CN)6]3- ions, a new
      absorption appeared in the visible light region (410 to 700 nm). Absorption
      spectroscopy measurements showed that Fe(iii)-CN-TiO2 was converted to Fe(ii)-CN
      TiO2 under visible light irradiation (>520 nm), which indicates that the new
      absorption was assignable to direct charge transfer from the valence band to the
      modified Fe(iii) ions.

PMID- 30101238
TI  - The role of Li+ in the upconversion emission enhancement of (YYbEr)2O3
      nanoparticles.
AB  - The mechanism of upconversion enhancement for Li+-doped materials is still
      contentious. Attempting to settle the debate, here the upconversion emission
      enhancement of (Y0.97-xYb0.02Er0.01Lix)2O3, x = 0.000-0.123, nanoparticles is
      studied. Li+ incorporation in the Y2O3 host lattice is achieved via co
      precipitation and solid-state reaction routes. In contrast to numerous reports,
      elemental analysis reveals that the former method does not afford Li+-bearing
      nanoparticles. The solid-state reaction route accomplishes an effective Li+
      doping, as witnessed by inductively coupled plasma atomic emission spectroscopy
      and X-ray photoelectron spectroscopy (XPS). Transmission electron microscopy and
      powder X-ray diffraction showed an increase in nanoparticle size with increasing
      Li+ concentration. Rietveld refinement of powder X-ray diffraction data shows
      that the cubic lattice parameter decreases with increasing Li+ content. The
      emission quantum yield increases tenfold with increasing Li+ content up to x =
      0.123, reaching a maximal value of 0.04% at x = 0.031. XPS and infrared
      spectroscopy show that the carbonate groups increase with increasing Li+ content,
      thus not supporting the prevailing view that the upconversion luminescence
      enhancement observed upon Li+ nanoparticle's doping is due to the decrease of the
      number of quenching carbonate groups present. Rather, the particle size increment
      and the decrease in the lattice parameter of the host crystals are shown to be
      the prime sources of quantum yield enhancement.

PMID- 30101239
TI  - Water-mediated network in the resistance mechanism of fosfomycin.
AB  - Fosfomycin Resistance Kinase A (FomA) catalyzes the phosphorylation of
      fosfomycin, which is an effective antibiotic for treating urinary tract
      infections. Understanding the chemical reaction mechanism is essential for
      developing strategies to counter the resistance of fosfomycin in clinical
      settings. Here the catalytic mechanism of FomA was investigated using molecular
      dynamic simulations in conjunction with quantum mechanics/molecular mechanics
      calculations (B97d/AMBER99). Our QM/MM study disclosed that the phosphorylation
      reaction catalyzed by FomA follows a dissociative mechanism, in contrast to the
      previously proposed associative mechanism. In addition, we found that His58, a
      characteristic residue in the AAK family, plays a key role in positioning the
      phosphate group of fosfomycin in the transition state. Molecular dynamic
      simulations revealed the important roles of Lys9 and Lys18 in arranging the
      nucleotide for phosphate transfer. Furthermore, we identified a four-membered
      water network mediated by Asp171 and Ser13 that is critical in ordering ATP for
      phosphate transfer. The active structure and reaction mechanism of FomA will
      provide valuable insights for developing new strategies to tackle the resistance
      to Fosfomycin-based antibiotic therapies.

PMID- 30101240
TI  - Incorporation of STED technique into single-molecule spectroscopy to break the
      concentration limit of diffusing molecules in single-molecule detection.
AB  - By incorporating STED (stimulated emission depletion) nanoscopy into single
      molecule spectroscopy, we demonstrate that the concentration limit imposed by
      optical diffraction can be overcome in diffusion-based single-molecule
      measurement. We showed that single-molecule detection is feasible at a
      concentration of 5 nM, which is 100-times higher than the limit of conventional
      single-molecule measurements.

PMID- 30101241
TI  - Multicarbazole scaffolds for selective G-quadruplex binding.
AB  - Herein we report a new class of G-quadruplex stabilising ligands,
      multicarbazoles, which display high G-quadruplex DNA selectivity in the presence
      of 250 times excess duplex DNA. We report the synthesis of these compounds in
      moderate to high yields. Ligands in the series with optimal G-quadruplex
      selectivity contain an N-propylamino chain length where the amino functionalities
      are either pyrrolidine or piperidine.

PMID- 30101242
TI  - Single-molecule tracking in live Yersinia enterocolitica reveals distinct
      cytosolic complexes of injectisome subunits.
AB  - In bacterial type 3 secretion, substrate proteins are actively transported from
      the bacterial cytoplasm into the host cell cytoplasm by a large membrane-embedded
      machinery called the injectisome. Injectisomes transport secretion substrates in
      response to specific environmental signals, but the molecular details by which
      the cytosolic secretion substrates are selected and transported through the type
      3 secretion pathway remain unclear. Secretion activity and substrate selectivity
      are thought to be controlled by a sorting platform consisting of the proteins
      SctK, SctQ, SctL, and SctN, which together localize to the cytoplasmic side of
      membrane-embedded injectisomes. However, recent work revealed that sorting
      platform proteins additionally exhibit substantial cytosolic populations and that
      SctQ reversibly binds to and dissociates from the cytoplasmic side of membrane
      embedded injectisomes. Based on these observations, we hypothesized that dynamic
      molecular turnover at the injectisome and cytosolic assembly among sorting
      platform proteins is a critical regulatory component of type 3 secretion. To
      determine whether sorting platform complexes exist in the cytosol, we measured
      the diffusive properties of the two central sorting platform proteins, SctQ and
      SctL, using live cell high-throughput 3D single-molecule tracking microscopy.
      Single-molecule trajectories, measured in wild-type and mutant Yersinia
      enterocolitica cells, reveal that both SctQ and SctL exist in several distinct
      diffusive states in the cytosol, indicating that these proteins form stable homo-
      and hetero-oligomeric complexes in their native environment. Our findings provide
      the first diffusive state-resolved insights into the dynamic regulatory network
      that interfaces stationary membrane-embedded injectisomes with the soluble
      cytosolic components of the type 3 secretion system.

PMID- 30101243
TI  - Induced circular dichroism of monoatomic anions: silica-assisted the transfer of
      chiral environment from molecular assembled nanohelices to halide ions.
AB  - We demonstrate the first example of induced CD of monoatomic anions. This was
      detected using chirally-arranged molecular assemblies of non-chiral cationic
      gemini surfactants (16-2-16) with monoatomic anions stabilized with silica
      coating. Furthermore, we have also achieved multi-step transfer of a chiral
      environment through an in situ chemical reaction via chiralized monoatomic
      anions.

PMID- 30101244
TI  - Doping-free circularly polarized electroluminescence of AIE-active chiral
      binaphthyl-based polymers.
AB  - AIE-active chiral polymer enantiomers (S-/R-P) can emit green circularly
      polarized electroluminescence (CP-EL) with gEL up to 0.024 without alignment
      layers and chiral dopants, which represents the first example of CP-OLEDs based
      on AIE-active main-chain chiral polymers.

PMID- 30101245
TI  - Co-assemblies of polydiacetylenes and metal ions for solvent sensing.
AB  - We demonstrate an easy and low-cost approach for the colorimetric differentiation
      of organic solvents using co-assemblies of polydiacetylenes (PDAs) and metal
      ions. The co-assemblies were prepared by the self-assembly of amphiphilic 10,12
      tricosa diynoic acid with different metal ions (Zn2+, Cu2+, Ni2+, Ca2+) and
      subsequent photopolymerization. Different metal ions underwent different
      interactions with the carboxyl groups on the side chains of poly(10,12-tricosa
      diynoic acid), which influenced the stimuli-responsiveness of the PDA/metal ion
      co-assemblies. As a result, the PDA/metal ion co-assemblies with different metal
      ions showed different solvatochromism. Based on this property, the co-assemblies
      were used as sensors to differentiate organic solvents.

PMID- 30101246
TI  - The effects of gut microbiota on metabolic outcomes in pregnant women and their
      offspring.
AB  - Metabolic diseases such as gestational diabetes mellitus and obesity during
      pregnancy have become severe health issues due to adverse pregnant outcomes in
      recent years. Maternal metabolic disorders can influence the long-term health of
      mothers and their offspring. Current evidence demonstrated that gut microbiota
      plays a crucial role in metabolic dysfunction during gestation. Maternal status
      is associated with alterations in the compositions and diversity of the
      intestinal microbiota community during gestation. Antibiotic treatments may
      disturb the gut microbiota of pregnant women, and scientific probiotic and
      prebiotic supplements have positive effects on mothers and their offspring. This
      review discusses the role of gut microbiota on metabolic outcomes in pregnant
      women and their offspring, and further illustrates the impact of interventions on
      metabolic disorders in pregnancy. Our study may provide a novel target for health
      management during pregnancy.

PMID- 30101247
TI  - The metal-ionic liquid interface as characterized by impedance spectroscopy and
      in situ scanning tunneling microscopy.
AB  - We summarize our results of electrochemical measurements carried out on inert or
      close-to-inert metals in ionic liquids, with the aim to explore the metal|ionic
      liquid interface structure. To this we used electrochemical methods: cyclic
      voltammetry, impedance spectroscopy, potential of zero total charge measurements
      and structure-sensitive techniques, such as in situ scanning tunneling
      spectroscopy. The studied systems were mostly single crystals of noble metals in
      imidazolium-based ionic liquids. The two main findings are: (i) in the potential
      window where no Faradaic reactions occur, the interfacial capacitance exhibits a
      frequency dependence due to double-layer rearrangement processes and (ii) in
      certain cases ordered anion and cation structures exist at the interface.

PMID- 30101249
TI  - Lanthanide-based tools for the investigation of cellular environments.
AB  - Biological probes constructed from lanthanides can provide a variety of readout
      signals, such as the luminescence of Eu(iii), Tb(iii), Yb(iii), Sm(iii) and
      Dy(iii), and the proton relaxation enhancement of Gd(iii) and Eu(ii). For
      numerous applications the intracellular delivery of the lanthanide probe is
      essential. Here, we review the methods for the intracellular delivery of non
      targeted complexes (i.e. where the overall complex structure enhances cellular
      uptake), as well as complexes attached to a targeting unit (i.e. to a peptide or
      a small molecule) that facilitates delivery. The cellular applications of
      lanthanide-based supramolecules (dendrimers, metal organic frameworks) are
      covered briefly. Throughout, we emphasize the techniques that can confirm the
      intracellular localization of the lanthanides and those that enable the
      determination of the fate of the probes once inside the cell. Finally, we
      highlight methods that have not yet been applied in the context of lanthanide
      based probes, but have been successful in the intracellular delivery of other
      metal-based probes.

PMID- 30101250
TI  - Inequivalence of fixed-force and fixed-extension statistical ensembles for a
      flexible polymer tethered to a planar substrate.
AB  - Recent advances in single macromolecule experiments have sparked interest in the
      ensemble dependence of force-extension relations. The thermodynamic limit may not
      be attainable for such systems, which leads to inequivalence of the fixed-force
      and the fixed-extension ensembles. We consider an ideal Gaussian chain described
      by the Edwards Hamiltonian with one end tethered to a rigid planar substrate. We
      analytically calculate the force-extension relation in the two ensembles and we
      show their inequivalence, which is caused by the confinement of the polymer to
      half space. The inequivalence is quite remarkable for strong compressional
      forces. We also perform Monte-Carlo simulations of a tethered wormlike chain with
      contour length 20 times its persistence length, which corresponds to experiments
      measuring the conformations of DNA tethered to a wall. The simulations confirm
      the ensemble inequivalence and qualitatively agree with the analytical
      predictions of the Gaussian model. Our analysis shows that confinement due to
      tethering causes ensemble inequivalence, irrespective of the polymer model.

PMID- 30101248
TI  - Molecular recognition of bio-active flavonoids quercetin and rutin by bovine
      hemoglobin: an overview of the binding mechanism, thermodynamics and structural
      aspects through multi-spectroscopic and molecular dynamics simulation studies.
AB  - The binding of two bio-active flavonoids, quercetin and rutin, with bovine
      hemoglobin (BHb) was investigated by multi-spectroscopic and computational
      (molecular docking and molecular dynamics simulation) studies. The two flavonoids
      were found to quench the intrinsic fluorescence of BHb through a static quenching
      mechanism. The binding constants at 288 K were observed to be (14.023 +/- 0.73) *
      104 M-1 and (7.848 +/- 0.20) * 104 M-1, respectively for quercetin and rutin
      binding with BHb. Both rutin and quercetin were observed to increase the polarity
      around the Trp residues of BHb as indicated by synchronous and 3D spectral
      studies. No significant alterations in the secondary structural components of the
      protein were caused during the binding of the flavonoids as studied by CD and
      FTIR studies. The negative molar Gibbs free energies indicated the spontaneity of
      the interaction processes while the binding processes were characterized by a
      negative enthalpy change (DeltaH) and a positive entropy change (DeltaS). The
      possibility of energy transfer from the donor (BHb) to the acceptor molecules
      (flavonoids) was indicated by the FRET studies. According to the fluorescence
      studies, the flavonoids interact near to the beta2-Trp37 residue of BHb.
      Excellent correlations with the experimental studies were observed from the
      molecular docking and molecular dynamics (MD) simulation studies. Further
      investigations established that these flavonoids are efficient in the inhibition
      of glucose mediated glycation of BHb.

PMID- 30101251
TI  - Choline chloride-based deep eutectic solvents for efficient cycloaddition of CO2
      with propylene oxide.
AB  - Choline chloride-based deep eutectic solvents (DESs) exhibited remarkable
      activity in the cycloaddition of CO2 with propylene oxide (PO) in the absence of
      any additives under solvent- and metal-free conditions as well as recyclability.

PMID- 30101252
TI  - Ruthenium-catalyzed synthesis of arylethyl 1,3,5-triazines from arylallyl
      alcohols and biguanides.
AB  - An efficient ruthenium-catalyzed synthesis of alkyl-1,3,5-triazies from arylallyl
      alcohols and biguanides has been developed. The reaction occurred in moderate to
      good yields and tolerated heterocyclic or aryl allyl alcohols containing
      functionalities such as alkanes, ethers, and halogens. The reaction proceeds
      through a one-pot sequence of transfer hydrogenation and condensation steps.

PMID- 30101253
TI  - Probing acid sites in solid catalysts with pyridine UV-Vis spectroscopy.
AB  - Solid acids hold widespread applications in the field of heterogeneous catalysis.
      In this work, we present pyridine UV-Vis spectroscopy as a novel and promising
      tool to study the acidic properties of such solid acids. It was found that upon
      interaction with acid sites, the electronic properties of pyridine change
      significantly. Monitoring of consecutive adsorption and desorption of pyridine
      revealed absorption bands in the UV-Vis region characteristic for (a) pyridinium
      ions formed on Bronsted acid sites, (b) pyridine coordinated to Lewis acid sites,
      (c) pyridine hydrogen-bonded to surface hydroxyl groups, and (d) physisorbed
      pyridine. The classical pyridine FT-IR method probes the presence of different
      Bronsted and Lewis acid sites as well, but lacks sensitivity towards the
      differentiation between surface hydroxyl groups. In contrast, the pyridine UV-Vis
      spectroscopy method proves especially useful for the identification and
      distinction of different surface hydroxyl groups, since the band position in the
      UV-Vis spectrum strongly depends on the chemical environment of the hydroxyl
      group. Moreover, utilizing a slow desorption procedure under N2 flow, it was
      possible to study the differences in acidic strength of the hydroxyl groups. This
      method and related measurement protocols were developed for the study of acidic
      properties within solid acids with different silica/alumina ratios, but are, in
      our opinion, more generally applicable to any solid acid.

PMID- 30101254
TI  - Structural effects on optoelectronic properties of halide perovskites.
AB  - Halide perovskites have prompted the evolution of the photovoltaic field and
      simultaneously demonstrated their great potential for application in other
      optoelectronic devices. A fundamental understanding of their structure-property
      relationship is essential to fabricate novel materials and high-performance
      devices. This review gives a perspective on different synthetic methodologies for
      the preparation of halide perovskites and highlights the effects of structural
      factors such as crystal structure, grain size, nanoscale dimensionality,
      patterned arrangement, and hierarchical structure on their optoelectronic
      properties. The main emphasis is given to 0D, 1D and 2D nanostructured materials
      including their common synthesis methods and key structural properties.
      Structural factors should be precisely controlled during the material preparation
      and device fabrication to improve the performance of targeted applications.

PMID- 30101255
TI  - Thermodynamic and kinetic isotope effects on the order-disorder transition of ice
      XIV to ice XII.
AB  - Isotope effects accompanying the order-disorder transition of ice XIV to ice XII
      are studied using calorimetry, X-ray diffraction, and dielectric spectroscopy.
      Particular emphasis is placed on the impact of the cooling rate applied during
      high-pressure production and during ambient-pressure recooling on the degree of
      hydrogen order in the low-temperature ice XIV phase. For specimens from D2O,
      ordering is harder to achieve in the sense that despite smaller cooling rates,
      the degree of order is less than in crystals produced from H2O. The degree of
      ordering can be quantified in terms of the Pauling entropy using calorimetry and
      manifests itself in structural and dynamical features that were examined using X
      ray diffraction and dielectric spectroscopy, respectively. In hydrogen chloride
      doped samples, H/D substitution was found to slow down the dipolar dynamics up to
      about 30-fold and shifts the order-disorder transition by 4-6 K. By contrast to
      earlier assumptions it is possible to reach a high degree of ordering also at
      ambient pressure, provided the cooling rate is small enough. That is, at ambient
      pressure, orthorhombic stress slows down the dipolar reorientation near the
      ordering transition by a factor of 300-2000 for H2O and 30-100 for D2O samples.
      Furthermore, by long-term storage of our samples at 77 K we have reached
      surprisingly large increases in degree of order. For the D2O samples we observed
      an unprecedented high order, corresponding to more than 45% of the Pauling
      entropy.

PMID- 30101256
TI  - Aqueous sodium hydroxide (NaOH) solutions at high pressure and temperature:
      insights from in situ Raman spectroscopy and ab initio molecular dynamics
      simulations.
AB  - Hydrothermal diamond anvil cell experiments in combination with Raman
      spectroscopy and first principles molecular dynamics simulations were performed
      to investigate the structure and dynamics of aqueous NaOH solutions for
      temperatures up to 700  degrees C, pressures up to 850 MPa and two different
      solute concentrations. The significant changes observed in the O-H stretching
      region of the Raman spectra between ambient and supercritical conditions are
      explained by both dynamic effects and structural differences. Especially
      important are a Grotthuss-like proton transport process and the decreasing
      network connectivity of the water molecules with increasing temperature. The
      observed transfer of Raman intensity towards lower wavenumbers by the proton
      transfer affects a wide range of frequencies and must be considered in the
      interpretation of Raman spectra of highly basic solutions. We suggest a
      deconvolution of the spectra using a model with four Gaussian functions, which
      are assigned to the molecular H2O and OH- vibrations, and one asymmetric
      exponentially modified Gaussian (EMG) function, which is assigned to [HO(H2O)n]-
      vibrations.

PMID- 30101257
TI  - Spectroscopic properties of LaGaO3:V,Nd3+ nanocrystals as a potential luminescent
      thermometer.
AB  - In this work we present the spectroscopic properties of LaGaO3:V,Nd3+
      nanocrystals, which have been successfully obtained by the Pechini method. This
      is the first study where vanadium ions were applied in a LaGaO3 lattice for a non
      contact luminescent thermometer. It was found that vanadium ions in the LaGaO3
      matrix appear in three oxidation states, namely V5+, V4+ and V3+. It was found
      that the relative emission intensities of various states of vanadium ions depend
      strongly on grain size and therefore the emission color of LaGaO3:V can be easily
      modulated via the annealing temperature. The spectroscopic properties of this
      material were investigated in a wide temperature range (-150-300  degrees C). It
      was found that in the case of V-singly doped nanocrystals, the V4+ ions, reveal
      the best temperature sensing performance with high relative sensitivity (S =
      1.76%  degrees C-1) and broad usable temperature range (-50-150  degrees C). The
      different rates of thermal luminescence quenching of the vanadium ions provide
      three forms of non-contact temperature sensor, namely LaGaO3:V5+,Nd3+,
      LaGaO3:V4+,Nd3+ and LaGaO3:V3+,Nd3+. The highest sensitivities were found to be
      1%  degrees C-1 (at -5  degrees C and 90  degrees C), 0.49%  degrees C-1 (at -20 
      degrees C) and 1.44%  degrees C-1 (at 75  degrees C) for LaGaO3:V5+,Nd3+,
      LaGaO3:V4+,Nd3+ and LaGaO3:V3+,Nd3+, respectively.

PMID- 30101258
TI  - A plug and socket approach for tightening polyelectrolyte multilayers.
AB  - A plug and socket approach for tightening polyelectrolyte multilayers is
      introduced based on the use pendant beta-cyclodextrin groups. Prototypical
      multilayers derived from poly(sodium 4-styrene sulfonate) and beta-cyclodextrin
      containing poly(4-vinylbenzyltrimethylammonium chloride) are described. Evidence
      for tightened multilayers has been obtained from gas permeation, swelling and
      quartz crystal microbalance with dissipation (QCM-D) measurements.

PMID- 30101259
TI  - Synthesis of 2-substituted 3-chlorobenzofurans via TMSCl-mediated nucleophilic
      annulation of isatin-derived propargylic alcohols.
AB  - A TMSCl-mediated cascade annulation of isatin-derived propargylic alcohols for
      the synthesis of 2-substituted 3-chlorobenzofurans is now reported. Mechanistic
      investigations showed that this proceeded through a sequential Meyer-Schuster
      rearrangement/nucleophilic addition/intramolecular annulation. TMSCl not only
      acts as a promoter, but also acts as a chlorine source in this protocol.

PMID- 30101260
TI  - Reactive convective-dissolution in a porous medium: stability and nonlinear
      dynamics.
AB  - We investigate the effects of a dissolution reaction, A(aq) + B(s) -> C(aq), on
      the gravitational instability and nonlinear dynamic behaviour of a diffusive
      boundary layer in a porous medium. Our linear stability and numerical results
      reveal that, unexpectedly, even when the density contribution of the soluble
      product C is smaller than that of the dissolved solute A, the chemical reaction
      can destabilize the layer and accelerate the onset of convection. However, for a
      very light product, the reaction stabilizes the layer. We show that these widely
      disparate characteristics of the reactive-diffusive layer are outcomes of the
      nonlinear competition between two reaction effects, the destabilizing sharpening
      of the solute concentration gradient and associated increase in the solute
      diffusive flux, and the stabilizing replacement of the solute by a less dense
      product near the interface.

PMID- 30101261
TI  - Ultrasensitive profiling of multiple biomarkers from single cells by signal
      amplification mass spectrometry.
AB  - A signal amplification protocol based on mass spectrometry (MS) was developed to
      profile simultaneously multiple biomarkers from a single cell using various mass
      label (ML)-modified Au nanoparticles (AuNPs). The strategy with ultrahigh
      sensitivity and specificity has potential prospects in the deep exploration of
      molecular and cellular characterization.

PMID- 30101262
TI  - Development of a novel durable aromatic anion exchange membrane using a thermally
      convertible precursor.
AB  - We describe a new approach for obtaining high-performance anion exchange
      membranes by using a thermally convertible precursor. A new insoluble all
      aromatic polymer containing anthracene units and benzyl trimethyl ammonium was
      successfully prepared from a highly soluble precursor polymer. The resulting
      polymer shows excellent chemical durability and conductivity.

PMID- 30101263
TI  - Functionalised microscale nanoband edge electrode (MNEE) arrays: the systematic
      quantitative study of hydrogels grown on nanoelectrode biosensor arrays for
      enhanced sensing in biological media.
AB  - Nanoelectrodes and nanoelectrode arrays show enhanced diffusion and greater
      faradaic current densities and signal-to-noise ratios compared to macro and
      microelectrodes, which can lead to enhanced sensing and detection. One example is
      the microsquare nanoband edge electrode (MNEE) array system, readily formed
      through microfabrication and whose quantitative response has been established
      electroanalytically. Hydrogels have been shown to have applications in drug
      delivery, tissue engineering, and anti-biofouling; some also have the ability to
      be grown electrochemically. Here, we combine these two emerging technologies to
      demonstrate the principles of a hydrogel-coated nanoelectrode array biosensor
      that is resistant to biofouling. We first electrochemically grow and analyze
      hydrogels on MNEE arrays. The structure of these gels is shown by imaging to be
      electrochemically controllable, reproducible and structurally hierarchical. This
      structure is determined by the MNEE array diffusion fields, consistent with the
      established hydrogel formation reaction, and varies in structural scale from nano
      (early time, near electrode growth) to micro (for isolated elements in the array)
      to macro (when there is array overlap) with distance from the electrode, forming
      a hydrogel mesh of increasing density on progression from solution to electrode.
      There is also increased hydrogel structural density observed at electrode
      corners, attributable to enhanced diffusion. The resulting hydrogel structure can
      be formed on (and is firmly anchored to/through) an established clinically
      relevant biosensing layer without compromising detection. It is also shown to be
      capable, through proof-of-principle model protein studies using bovine serum
      albumin (BSA), of preventing protein biofouling whilst enabling smaller molecules
      such as DNA to pass through the hydrogel matrix and be sensed. Together, this
      demonstrates a method for developing reproducible, quantitative electrochemical
      nanoelectrode biosensors able to sense selectively in real-world sample matrices
      through the tuning of their interfacial properties.

PMID- 30101264
TI  - Li doped kagome spin liquid compounds.
AB  - Herbertsmithite and Zn-doped barlowite are two compounds for experimental
      realization of two-dimensional kagome spin liquids. Theoretically, it has been
      proposed that charge doping a quantum spin liquid gives rise to exotic metallic
      states, such as high-temperature superconductivity. However, one recent
      experiment on herbertsmithite with successful Li-doping surprisingly showed an
      insulating state even under a heavily doped scenario, which cannot be explained
      by previous theories. Using first-principles calculations, we performed a
      comprehensive study on the Li intercalation doping effect of these two compounds.
      For the Li-doped herbertsmithite, we identified the optimized Li position at the
      Cl-(OH)3-Cl pentahedron site instead of the previously speculated Cl-(OH)3
      tetrahedral site. With increasing Li doping concentration, saturation
      magnetization decreases linearly due to charge transfer from Li to Cu ions.
      Moreover, we found that Li forms chemical bonds with nearby (OH)- and Cl- ions,
      which lowers the surrounding chemical potential and traps electrons, as evidenced
      by the localized charge distribution, explaining the insulating behavior measured
      experimentally. Though a different structure from herbertsmithite, Zn-doped
      barlowite shows the same features upon Li doping. We conclude that Li doping this
      family of kagome spin liquids cannot realize exotic metallic states, and other
      methods should be further explored, such as element substitution with those
      having different valence electrons.

PMID- 30101265
TI  - The viscous consequence of different trends in clustering of 1,2-diol and 1,n
      diol molecules.
AB  - This paper presents the molecular basis for the quite different behavior of the
      viscosity of 1,2- and 1,n-diols in dependence of the length of the alkyl part of
      the molecules of these compounds. The experimental data on the dipolar
      orientational effects revealed a decidedly different role of that part of the
      molecules in creating a microstructure of both the hydrogen-bonded liquids. In
      the case of 1,n-diols, an increase in the alkyl radical length, i.e. an
      increasing of the distance between the OH groups within the molecule, highly
      stimulates molecular self-assembly in form of gradually longer and wider ribbon
      like clusters. This effect yields a quite important increase in the viscosity of
      1,n-diols as n increases. In the case of 1,2-diols, due to gradual separation of
      the hydrophilic and hydrophobic parts of the molecules, the situation is quite
      different. Two OH groups situated on one of the ends of the hydrocarbon radical
      form the clusters of a micelle-like shape, however, the dipole moment is not
      compensated. Along with an increase in the hydrocarbon part in 1,2-diol
      molecules, one only observes an increase in the intermolecular consolidation
      within the micelle-like entities. This manifests as a gradual decrease in the
      polarity of these clusters. So, actually, there are no relevant reasons for
      essential differences of viscosities in the series of 1,2-diols.

PMID- 30101266
TI  - Unveiling the effects of A-site substitutions on the oxygen ion migration in A2
      xA'xNiO4+delta by first principles calculations.
AB  - The effects of A-site substitutions on the interstitial oxygen formation energy
      and the migration energy in layered A2-xA'xNiO4+delta (A = selected lanthanides,
      A' = Ba, Sr, Ca) are investigated by first principles calculations. The
      interstitial oxygen formation energy is negative, in the range of -4.81 eV to 
      3.45 eV, strongly supporting easiness of formation of the interstitial oxygen
      defects in the (A,A')O rock salt plane. The Pr2NiO4+delta compound shows the
      lowest formation energy, indicating the highest amount of interstitial oxygen.
      Doping with alkaline earth cations (A') increases the formation energy of the
      interstitial oxygen, which prefers to be located far away from the dopants.
      Nevertheless, Ca seems to be the best choice, due to relatively low formation
      energy. Calculations for the four kinds of diffusion paths allow it to be
      predicted that the oxygen transport in A2-xA'xNiO4+delta is governed by the
      interstitialcy mechanism in the ab plane, because of the significantly lower
      energy barriers for this mechanism. An interesting finding is achieved for
      A2NiO4+delta (A = Pr, Nd, Sm), for which the energy barriers for the
      interstitialcy transport are negative (-0.47 eV, -0.33 eV and -0.02 eV,
      respectively), implying that the transition state is more stable than the assumed
      initial state. A new structural configuration is proposed in this work, with the
      adjacent apical oxygen located at the adjacent interstitial site, which shows ca.
      0.5 eV lower free energy than that of the initial model. This result provides a
      new understanding for the location of the interstitial and the adjacent apical
      oxygens from an energetic point of view and supports previously published
      experimental data. It is found that alkaline earth doping at the A-site
      deteriorates the interstitial oxygen diffusion in La2-xA'xNiO4.25 materials, but
      concerning overall transport properties, Ca seems to be a good dopant from an
      energetic point of view, when compared with Ba and Sr.

PMID- 30101268
TI  - Radicals generated in alternating guanine-cytosine duplexes by direct absorption
      of low-energy UV radiation.
AB  - Recent studies have evidenced that oxidatively damaged DNA, which potentially
      leads to carcinogenic mutations and aging, may result from the direct absorption
      of low-energy photons (>250 nm). Herein, the primary species, i.e., ejected
      electrons and base radicals associated with such damage in duplexes with an
      alternating guanine-cytosine sequence are quantified by nanosecond transient
      absorption spectroscopy. The one-photon ionization quantum yield at 266 nm is 1.2
      * 10-3, which is similar to those reported previously for adenine-thymine
      duplexes. This means that the simple presence of guanine, the nucleobase with the
      lowest ionization potential, does not affect photo-ionization. The transient
      species detected after 3 MUs are identified as deprotonated guanine radicals,
      which decay with a half-time of 2.5 ms. Spectral assignment is made with the help
      of quantum chemistry calculations (TD-DFT), which for the first time, provide
      reference absorption spectra for guanine radicals in duplexes. In addition, our
      computed spectra predict the changes in transient absorption expected for hole
      localization as well as deprotonation (to cytosine and bulk water) and hydration
      of the radical cation.

PMID- 30101267
TI  - A tumor-targeting probe based on a mitophagy process for live imaging.
AB  - A glucosamine modified near-infrared cyanine dye CyT sensitive to pH was
      synthesized. Due to the different pH values of mitochondria and autolysosomes,
      the probe can simultaneously investigate mitochondria and autolysosomes in living
      cells. Moreover, due to the introduction of glucosamine groups, this fluorescent
      probe can be applied for tumor targeted imaging.

PMID- 30101269
TI  - A CuO-functionalized NMOF probe with a tunable excitation wavelength for
      selective detection and imaging of H2S in living cells.
AB  - Recently, fluorescent nanoscale metal-organic frameworks (NMOFs) have been proven
      to be useful probes for the detection and imaging of active biomolecules in
      living cells. However, the excitation wavelengths of these NMOF fluorescence
      probes are mostly in the ultraviolet region, which unavoidably results in reduced
      cell activity, limited tissue penetration depth and inevitable biological
      background interference. Herein, to solve this problem, a CuO functionalized NMOF
      probe with a tunable excitation wavelength based on Forster resonance energy
      transfer (FRET) for selective detection and imaging of the third important
      gaseous signaling molecule hydrogen sulfide (H2S) in living cells as an example
      is presented. In the energy transfer system, NMOF confines the luminophore
      organic dye thiazole orange within its intrinsic porous matrix as the energy
      donor, in which the excitation wavelength of the NMOF can be tuned simply from UV
      to Vis through the choice of dye molecules, and the H2S-responding site copper
      oxide nanoparticle (CuO NP) is the acceptor. After the surface functionalization
      of CuO NPs onto the NMOF, the fluorescence of the NMOF can be efficiently
      quenched based on the FRET. When H2S appeared, the fluorescence of the nanoprobe
      is recovered due to the interruption of FRET. This facile yet powerful strategy
      not only provides an instantaneous fluorescence probe for selective H2S detection
      in living cells but also offers a valuable approach for using porous NMOFs to
      sense other biological species.

PMID- 30101271
TI  - Iodine-catalyzed synthesis of N,N'-diaryl-o-phenylenediamines from cyclohexanones
      and anilines using DMSO and O2 as oxidants.
AB  - A novel I2-catalyzed cross-dehydrogenative aromatization of cyclohexanones and
      anilines to synthesize N,N'-diaryl-o-phenylenediamines has been unprecedentedly
      developed with dimethyl sulfoxide and oxygen employed as mild terminal oxidants.
      To prove the rationality of the two separate dehydration steps of the proposed
      mechanism, a resulting I2-catalyzed cross-dehydrogenative aromatization of
      cyclohexenones and anilines to synthesize diarylamines has also been reported.

PMID- 30101270
TI  - Approaching single DNA molecule detection with an ultrasensitive electrochemical
      genosensor based on gold nanoparticles and cobalt-porphyrin DNA conjugates.
AB  - We describe an ultrasensitive electrochemical genosensor based on gold
      nanoparticles and cobalt-porphyrin functionalised ssDNA probes. The sensitivity
      at the attomolar concentration level arises from an increased density of redox
      labels on the electrode surface compared to sensors without NP modification. The
      electrode detects as few as 23 DNA molecules, approaching single molecule
      detection.

PMID- 30101272
TI  - Radicals in natural product synthesis.
AB  - Free radical intermediates have intrigued chemists since their discovery, and an
      ever-increasing appreciation for their unique reactivity has resulted in the
      widespread utilization of these species throughout the field of chemical
      synthesis. This is most evident from the recent surge in the application of
      intermolecular radical reactions that feature in complex molecule syntheses. This
      tutorial review will discuss the diverse methods utilized for radical generation
      and reactivity to form critical bonds in natural product total synthesis. In
      particular, stabilized (e.g. benzyl) and persistent (e.g. TEMPO) radicals will be
      the primary focus.

PMID- 30101274
TI  - Chemoselective N-H functionalization of indole derivatives via the Reissert-type
      reaction catalyzed by a chiral phosphoric acid.
AB  - An asymmetric N-alkylation of indole derivatives via the Reissert-type reaction
      was realized in the presence of a catalytic amount of chiral phosphoric acid.
      Various enantioenriched indoles with N-1 substituted by 1,2-dihydroisoquinoline
      could be obtained under mild conditions in good yields and enantioselectivities
      at room temperature (up to 98% yield, 94% ee). The current method is compatible
      with gram-scale reaction and the products can undergo versatile chemical
      transformations.

PMID- 30101273
TI  - Targeting STING with cyclic di-GMP greatly augmented immune responses of
      glycopeptide cancer vaccines.
AB  - Cyclic di-GMP (CDG) was applied to MUC1 glycopeptide-based cancer vaccines with
      physical mixing and built-in (at 2'-OH of CDG) strategies for activating the
      STING pathway. CDG in both strategies behaved as a potent immunostimulant and
      contributed to high titers of IgG antibodies and the expression of multiple
      cytokines.

PMID- 30101275
TI  - KEDDY: a knowledge-based statistical gene set test method to detect differential
      functional protein-protein interactions.
AB  - Motivation: Identifying differential patterns between conditions is a popular
      approach to understanding the discrepancy between different biological contexts.
      Although many statistical tests were proposed for identifying gene sets with
      differential patterns based on different definitions of differentiality, few
      methods were suggested to identify gene sets with differential functional protein
      networks due to computational complexity. Results: We propose a method of
      Knowledge-based Evaluation of Dependency DifferentialitY (KEDDY), which is a
      statistical test for differential functional protein networks of a set of genes
      between two conditions with utilizing known functional protein-protein
      interaction information. Unlike other approaches focused on differential
      expressions of individual genes or differentiality of individual interactions,
      KEDDY compares two conditions by evaluating the probability distributions of
      functional protein networks based on known functional protein-protein
      interactions. The method has been evaluated and compared with previous methods
      through simulation studies, where KEDDY achieves significantly improved
      performance in accuracy and speed than the previous method that does not use
      prior knowledge and better performance in identifying gene sets with differential
      interactions than other methods evaluating changes in gene expressions.
      Applications to cancer data sets show that KEDDY identifies alternative cancer
      subtype-related differential gene sets compared to other differential expression
      based methods, and the results also provide detailed gene regulatory information
      that drives the differentiality of the gene sets. Availability and implemtation:
      The Java implementation of KEDDY is freely available to non-commercial users at
      https://sites.google.com/site/sjunggsm/keddy. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30101276
TI  - A guide to policy analysis as a research method.
AB  - Policy analysis provides a way for understanding how and why governments enact
      certain policies, and their effects. Public health policy research is limited and
      lacks theoretical underpinnings. This article aims to describe and critique
      different approaches to policy analysis thus providing direction for undertaking
      policy analysis in the field of health promotion. Through the use of an
      illustrative example in nutrition it aims to illustrate the different approaches.
      Three broad orientations to policy analysis are outlined: (i) Traditional
      approaches aim to identify the 'best' solution, through undertaking objective
      analyses of possible solutions. (ii) Mainstream approaches focus on the
      interaction of policy actors in policymaking. (iii) Interpretive approaches
      examine the framing and representation of problems and how policies reflect the
      social construction of 'problems'. Policy analysis may assist understanding of
      how and why policies to improve nutrition are enacted (or rejected) and may
      inform practitioners in their advocacy. As such, policy analysis provides
      researchers with a powerful tool to understand the use of research evidence in
      policymaking and generate a heightened understanding of the values, interests and
      political contexts underpinning policy decisions. Such methods may enable more
      effective advocacy for policies that can lead to improvements in health.

PMID- 30101277
TI  - White striping and wooden breast myopathies of broiler breast muscle is affected
      by time-limited feeding, genetic background, and egg storage.
AB  - The effects of time-limited feeding, genetic background, and egg storage on white
      striping (WS) and wooden breast (WB) in broilers were studied. Male chicks (240)
      from 2 genetic backgrounds and 2 egg storage periods were fed on either an ad
      libitum (AL) or time-limited (TL) program from 7 d of age. A rapid growth strain
      (Growth) and an enhanced yield strain (Yield) of broiler breeder males were mated
      to a single female line and eggs were stored for periods of either 1 to 7 d or 8
      to 14 d. Body weight (BW), feed consumption, and feed conversion ratio (FCR) were
      determined weekly. Carcass data including WS and WB scores were collected at 42 d
      of age. Breast muscle scoring was conducted either visually or by hand palpation
      using a 1 to 4 point ordinal scale (normal to greatest severity). Data were
      analyzed using the Mixed procedure of SAS. The TL fed broilers presented less WS
      (1.64 vs. 2.87) and WB (2.14 vs. 2.89), lower BW (2.99 vs. 3.27 kg), and improved
      FCR (1.55 vs. 1.58 g: g), as well as reduced dressing percentage (79.5 vs.
      80.1%), breast muscle yield (33.3 vs. 34.6%), and 24 h muscle pH (5.82 vs. 5.95)
      relative to AL broilers (P < 0.01). Yield broilers exhibited reduced BW (2.97 vs.
      3.28 kg), lower WS (2.04 vs. 2.47), and greater WB (2.65 vs. 2.38) (P < 0.05) but
      similar dressing percentage (80.0 vs. 79.7%) and breast muscle yield (34.3 vs.
      33.6%) when compared to Growth broilers. Longer egg storage generated lower BW
      (3.07 vs. 3.18 kg) and when fed AL, an increased WS score (2.58 vs. 3.15)
      compared to the shorter egg storage period (P < 0.05). It was concluded that WS
      and WB could be reduced by TL feeding and that genetic background and egg storage
      period may influence the expression of WS and WB.

PMID- 30101278
TI  - Influence of Intravenous Fentanyl Compared with Morphine on Ticagrelor Absorption
      and Platelet Inhibition in Patients with St-Segment Elevation Myocardial
      Infarction Undergoing Primary Percutaneous Coronary Intervention: Rationale and
      Design of the Perseus Randomized Trial.
AB  - Background and aims: Recent evidence demonstrates that intravenous morphine
      significantly reduces absorption and delays onset of action of oral P2Y12
      receptor inhibitors in patients with ST-segment elevation myocardial infarction
      (STEMI) undergoing primary percutaneous coronary intervention (pPCI). We aimed to
      assess the influence of intravenous fentanyl compared with morphine on
      pharmacokinetics (PK) and pharmacodynamics (PD) of ticagrelor and its active
      metabolite (AR-C124910XX) in patients undergoing pPCI for STEMI. Methods: Single
      center, prospective, open-label, randomized controlled study that will randomly
      assign in a 1:1 ratio patients with STEMI undergoing pPCI to receive intravenous
      fentanyl or morphine following a pre-hospital 180-mg loading dose (LD) of
      ticagrelor (ClinicalTrials.gov Identifier: NCT02531165). PK/PD analyses will be
      performed at baseline and 1, 2, 4, 6 and 12 hours post-LD). PD assessments will
      include P2Y12 reaction units (PRU) measured by VerifyNow P2Y12. PK assessments
      include determination of maximal observed plasma concentrations, time for maximal
      plasma concentration, and area under the plasma concentration versus time curve
      from time 0 to the last measurable concentration (AUC0-t) for ticagrelor and AR
      C124910XX. The primary endpoint is platelet reactivity assessed by PRU at 2 hours
      post-LD. Conclusions: PERSEUS will provide data regarding the impact of fentanyl
      administration, in patients with STEMI undergoing pPCI, on platelet inhibition
      and ticagrelor absorption and total exposure.

PMID- 30101280
TI  - Neurosurgical Coverage for Emergency and Trauma Call.
AB  - Traditionally, neurosurgeons have responded to calls to treat new patients or
      address emergent, acute neurosurgical pathology in the hospitals they staff as
      part of their duty to the medical profession and community. Due to increasing
      financial pressures placed upon neurosurgical practice from hospitals and
      regulatory mandates, remuneration for neurosurgeon availability to serve on
      trauma call has become more frequent and is increasingly seen as essential. In
      this study, we present the first peer-review published survey of neurosurgical
      emergency and trauma call coverage patterns, scope, schedules, compensation,
      liability exposure, and call cessation. We surveyed all practicing neurosurgeon
      members of the American Association of Neurological Surgeons and Congress of
      Neurological Surgeons with a 24% response rate. The vast majority of respondents
      (86%), through their practice, provide 24/7/365 trauma coverage at their primary
      hospital site. About a third (29%) of respondents have been sued by a patient
      seen in the emergency department. Twenty percent of respondents anticipate
      retiring within the next 2 yr. Understanding trauma call coverage, remuneration,
      and the barriers to taking call provide needed transparency to neurosurgeons who
      are providing emergency, life-saving services for patients across the country. An
      understanding of supply and demand forces governing call coverage also assists
      the field in necessary workforce planning and innovation in providing access to
      needed, timely acute neurosurgical care.

PMID- 30101281
TI  - Hypoglycemia After Gastric Bypass Surgery: Current Concepts and Controversies.
AB  - Context: Hypoglycemia, occurring after bariatric and other forms of upper
      gastrointestinal surgery, is increasingly encountered by clinical
      endocrinologists. The true frequency of this condition remains uncertain, due, in
      part, to differences in the diagnostic criteria and in the affected populations,
      as well as relative lack of patient and physician awareness and understanding of
      this condition. Postbariatric hypoglycemia can be severe and disabling for some
      patients, with neuroglycopenia (altered cognition, seizures, and loss of
      consciousness) leading to falls, motor vehicle accidents, and job and income
      loss. Moreover, repeated episodes of hypoglycemia can result in hypoglycemia
      unawareness, further impairing safety and requiring the assistance of others to
      treat hypoglycemia. Objective: In this review, we summarize and integrate data
      from studies of patients affected by hypoglycemia after Roux-en-Y gastric bypass
      (RYGB) surgery, obtained from PubMed searches (1990 to 2017) and reference
      searches of relevant retrieved articles. Whereas hypoglycemia can also be
      observed after sleeve gastrectomy and fundoplication, this review is focused on
      post-RYGB, given the greater body of published clinical studies at present.
      Outcome Measures: Data addressing specific aspects of diagnosis, pathophysiology,
      and treatment were reviewed by the authors; when not available, the authors have
      provided opinions based on clinical experience with this challenging condition.
      Conclusions: Hypoglycemia, occurring after gastric bypass surgery, is challenging
      for patients and physicians alike. This review provides a systematic approach to
      diagnosis and treatment based on the underlying pathophysiology.

PMID- 30101279
TI  - Consensus on Shared Measures of Mobility and Cognition: From the Canadian
      Consortium on Neurodegeneration in Aging (CCNA).
AB  - Background: A new paradigm is emerging in which mobility and cognitive
      impairments, previously studied, diagnosed, and managed separately in older
      adults, are in fact regulated by shared brain resources. Deterioration in these
      shared brain mechanisms by normal aging and neurodegeneration increases the risk
      of developing dementia, falls, and fractures. This new paradigm requires an
      integrated approach to measuring both domains. We aim to identify a complementary
      battery of existing tests of mobility and cognition in community-dwelling older
      adults that enable assessment of motor-cognitive interactions. Methods: Experts
      on mobility and cognition in aging participated in a semistructured consensus
      based on the Delphi process. After performing a scoping review to select
      candidate tests, multiple rounds of consultations provided structured feedback on
      tests that captured shared characteristics of mobility and cognition. These tests
      needed to be sensitive to changes in both mobility and cognition, applicable
      across research studies and clinics, sensitive to interventions, feasible to
      perform in older adults, been previously validated, and have minimal
      ceiling/floor effects. Results: From 17 tests appraised, 10 tests fulfilled
      prespecified criteria and were selected as part of the "Core-battery" of tests.
      The expert panel also recommended a "Minimum-battery" of tests that included gait
      speed, dual-task gait speed, the Montreal Cognitive Assessment and Trail Making
      Test A&B. Conclusions: A standardized assessment battery that captures shared
      characteristics of mobility and cognition seen in aging and neurodegeneration may
      increase comparability across research studies, detection of subtle or common
      reversible factors, and accelerate research progress in dementia, falls, and
      aging-related disabilities.

PMID- 30101282
TI  - CABS-flex standalone: a simulation environment for fast modeling of protein
      flexibility.
AB  - Summary: CABS-flex standalone is a Python package for fast simulations of protein
      structure flexibility. The package combines simulations of protein dynamics using
      CABS coarse-grained protein model with the reconstruction of selected models to
      all-atom representation and analysis of modeling results. CABS-flex standalone is
      designed to allow for command-line access to the CABS computations and complete
      control over simulation process. CABS-flex standalone is equipped with features
      such as: modeling of multimeric and large-size protein systems, contact map
      visualizations, analysis of similarities to the reference structure and
      configurable modeling protocol. For instance, the user may modify the simulation
      parameters, distance restraints, structural clustering scheme or all-atom
      reconstruction parameters. With these features CABS-flex standalone can be easily
      incorporated into other methodologies of structural biology. Availability and
      Implementation: CABS-flex standalone is distributed under the MIT license, which
      is free for academic and non-profit users. It is implemented in Python. CABS-flex
      source code, wiki with examples of use and installation instructions for Linux,
      macOS and Windows are available from the CABS-flex standalone repository at
      https://bitbucket.org/lcbio/cabsflex.

PMID- 30101284
TI  - Translational insights into gastrointestinal stromal tumor and current clinical
      advances.
AB  - Gastrointestinal stromal tumor (GIST) is the most common soft tissue sarcoma of
      the gastrointestinal tract and, in the vast majority of cases, is characterized
      by activating mutations in KIT or, less commonly, PDGFRA. Mutations in these type
      III receptor tyrosine kinases (RTKs) account for over 85% of GIST cases, and the
      majority of KIT primary mutations respond to treatment with the tyrosine kinase
      inhibitor (TKI) imatinib. However, drug resistance develops over time, most
      commonly due to secondary kinase mutations. Sunitinib and regorafenib are
      approved for the treatment of imatinib-resistant GIST in the second and third
      lines, respectively. However, resistance to these agents also develops and new
      therapeutic options are needed. In addition, a small number of GISTs harbor
      primary activating mutations that are resistant to currently available TKIs,
      highlighting an additional unmet medical need. Several novel and selective TKIs
      that overcome known mechanisms of resistance in GIST have been developed and show
      promise in early clinical trials. Additional emerging targeted therapies in GIST
      include modulation of cellular signaling pathways downstream of KIT, antibodies
      targeting KIT and PDGFRA and immune checkpoint inhibitors. These advancements
      highlight the rapid evolution in the understanding of this malignancy and provide
      perspective on the encouraging horizon of current and forthcoming therapeutic
      strategies for GIST.

PMID- 30101283
TI  - Bioinformatics applications on Apache Spark.
AB  - With the rapid development of next-generation sequencing technology, ever
      increasing quantities of genomic data pose a tremendous challenge to data
      processing. Therefore, there is an urgent need for highly scalable and powerful
      computational systems. Among the state-of-the-art parallel computing platforms,
      Apache Spark is a fast, general-purpose, in-memory, iterative computing framework
      for large-scale data processing that ensures high fault tolerance and high
      scalability by introducing the resilient distributed dataset abstraction. In
      terms of performance, Spark can be up to 100 times faster in terms of memory
      access and 10 times faster in terms of disk access than Hadoop. Moreover, it
      provides advanced application programming interfaces in Java, Scala, Python, and
      R. It also supports some advanced components, including Spark SQL for structured
      data processing, MLlib for machine learning, GraphX for computing graphs, and
      Spark Streaming for stream computing. We surveyed Spark-based applications used
      in next-generation sequencing and other biological domains, such as epigenetics,
      phylogeny, and drug discovery. The results of this survey are used to provide a
      comprehensive guideline allowing bioinformatics researchers to apply Spark in
      their own fields.

PMID- 30101285
TI  - Hydroxyl radical-induced early stage oxidation improves the foaming and
      emulsifying properties of ovalbumin.
AB  - As the most abundant protein in chicken eggs, ovalbumin plays an important role
      in the processing of high value-added poultry products. The present study
      investigated the effects of hydroxyl radical-induced early stage oxidation on the
      physicochemical and interfacial properties of chicken egg white ovalbumin.
      Protein carbonyl content of ovalbumin increased (from 0.78 to 1.13 nmol/mg) with
      the oxidation time (0-5 h), while free sulfhydryl content (from 0.43 to 0.09
      nmol/mg) and free amino group content (from 0.49 to 0.43 nmol/mg) decreased.
      Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis showed that
      the exposure of ovalbumin to hydroxyl radicals caused self-cross-linking and
      resulted in the formation of dimers and trimers. Accompanied by these changes,
      the surface hydrophobicity of ovalbumin was enhanced about 1.5-fold with the
      deepening of oxidation, and the value of zeta potential became more negative
      (from -7.15 to -20.51 mv). About 2 h of moderate oxidation improved the foaming
      and emulsifying properties of ovalbumin (1.2-fold to 1.8-fold), while excessive
      oxidation (3 h) decreased these interface properties. Hydroxyl radical-induced
      oxidation changed the surface chemical groups and structures of ovalbumin,
      thereby affecting the surface properties. The foaming and emulsifying properties
      of ovalbumin could be improved by oxidation, increasing the application
      possibilities of ovalbumin in the food interface system.

PMID- 30101287
TI  - RhERF113 Functions in Ethylene-induced Petal Senescence by Modulating Cytokinin
      Content in Rose.
AB  - In rose (Rosa hybrida), flower senescence is accelerated by ethylene and delayed
      by cytokinins (CTKs). However, the effectors that regulate these processes are
      not currently understood. In this study, we identified an APETALA2/ethylene
      responsive factor (AP2/ERF) gene, RhERF113, which was induced by ethylene and
      upregulated during flower senescence in most floral organs, including sepal,
      petal, stamen, and pistil. The virus-induced gene silencing (VIGS) of RhERF113
      expression accelerated rose flower senescence, which was accompanied by a lower
      CTK content in the flowers. This accelerated senescence could be restored by
      exogenous CTK treatment. Moreover, the expression levels of genes related to CTK
      biosynthesis and signaling, including ISOPENTENYL TRANSFERASE 5 (RhIPT5), RhIPT8,
      HIS KINASE 2 (RhHK2), RhHK3, CYTOKININ RESPONSE REGULATOR 3 (RhCRR3), RhCRR5,
      RhCRR8, HOMEOBOX PROTEIN 6 (RhHB6), and PATHOGENESIS-RELATED 10.1 (RhPR10.1),
      were decreased in the RhERF113-silenced rose flowers. Taken together, our results
      demonstrate that RhERF113 delays ethylene-induced flower senescence by increasing
      the CTK content of the floral tissues.

PMID- 30101286
TI  - Tracing back multidrug-resistant bacteria in fresh herb production: from chive to
      source through the irrigation water chain.
AB  - Environmental antibiotic-resistant bacteria (ARB) can be transferred to humans
      through foods. Fresh produce in particular is an ideal vector due to frequent raw
      consumption. A major contamination source of fresh produce is irrigation water.
      We hypothesized that water quality significantly affects loads of ARB and their
      diversity on fresh produce despite various other contamination sources present
      under agricultural practice conditions. Chive irrigated from an open-top
      reservoir or sterile-filtered water (control) was examined. Heterotrophic plate
      counts (HPC) and ARB were determined for water and chive with emphasis on
      Escherichia coli and Enterococcus spp. High HPC of freshly planted chive
      decreased over time and were significantly lower on control- vs. reservoir
      irrigated chive at harvest (1.3 log (CFU/g) lower). Ciprofloxacin- and
      ceftazidime-resistant bacteria were significantly lower on control-irrigated
      chive at harvest and end of shelf life (up to 1.8 log (CFU/g) lower). Escherichia
      coli and Enterococcus spp. repeatedly isolated from water and chive proved
      resistant to up to six or four antibiotic classes (80% or 49% multidrug
      resistant, respectively). Microbial source tracking identified E. coli-ST1056
      along the irrigation chain and on chive. Whole-genome sequencing revealed that E.
      coli-ST1056 from both environments were clonal and carried the same transmissible
      multidrug-resistance plasmid, proving water as source of chive contamination.
      These findings emphasize the urgent need for guidelines concerning ARB in
      irrigation water and development of affordable water disinfection technologies to
      diminish ARB on irrigated produce.

PMID- 30101288
TI  - An Innovative Study Design to Assess the Community Effect of Interventions to
      Mitigate HIV Epidemics Using Transmission-Chain Phylodynamics.
AB  - Given globalization and other social phenomena, controlling the spread of
      infectious diseases has become an imperative public health priority. A plethora
      of interventions that in theory can mitigate the spread of pathogens have been
      proposed and applied. Evaluating the effectiveness of such interventions is
      costly and in many circumstances unrealistic. Most important, the community
      effect (i.e., the ability of the intervention to minimize the spread of the
      pathogen from people who received the intervention to other community members)
      can rarely be evaluated. Here we propose a study design that can build and
      evaluate evidence in support of the community effect of an intervention. The
      approach exploits molecular evolutionary dynamics of pathogens in order to track
      new infections as having arisen from either a control or an intervention group.
      It enables us to evaluate whether an intervention reduces the number and length
      of new transmission chains in comparison with a control condition, and thus lets
      us estimate the relative decrease in new infections in the community due to the
      intervention. We provide as an example one working scenario of a way the approach
      can be applied with a simulation study and associated power calculations.

PMID- 30101290
TI  - The absence of thioredoxin m1 and thioredoxin C in Anabaena sp. PCC 7120 leads to
      oxidative stress.
AB  - Thioredoxin (Trx) family proteins perform redox regulation in cells, and they are
      involved in several other biological processes (e.g., oxidative stress
      tolerance). In the filamentous cyanobacterium Anabaena sp. PCC7120 (A. 7120),
      eight Trx isoforms have been identified via genomic analysis. Among these Trx
      isoforms, the absence of Trx-m1 and TrxC appear to result in oxidative stress in
      A. 7120 together with alterations of the thylakoid membrane structure and
      phycobiliprotein composition. To thoroughly analyze the physiological changes in
      these Trx disruptants, quantitative proteomics was applied. Certainly, the
      mutants exhibited similar alternation in the proteome including decreased
      relative abundance of phycobiliproteins and increased level of proteins involved
      in amino acid and carbohydrate metabolisms. Nevertheless, the results also
      indicated that the mutants exhibited changes in the relative abundance of
      different sets of proteins participating in reactive oxygen species
      detoxification, such as Fe-SOD in Deltatrx-m1 and PrxQ in DeltatrxC, suggesting
      distinct functions of Trx-m1 and TrxC.

PMID- 30101289
TI  - Microbial community composition of a hydrocarbon reservoir 40 years after a CO2
      enhanced oil recovery flood.
AB  - Injecting CO2 into depleted oil reservoirs to extract additional crude oil is a
      common enhanced oil recovery (CO2-EOR) technique. However, little is known about
      how in situ microbial communities may be impacted by CO2 flooding, or if any
      permanent microbiological changes occur after flooding has ceased. Formation
      water was collected from an oil field that was flooded for CO2-EOR in the 1980s,
      including samples from areas affected by or outside of the flood region, to
      determine the impacts of CO2-EOR on reservoir microbial communities. Archaea,
      specifically methanogens, were more abundant than bacteria in all samples, while
      identified bacteria exhibited much greater diversity than the archaea. Microbial
      communities in CO2-impacted and non-impacted samples did not significantly differ
      (ANOSIM: Statistic R = -0.2597, significance = 0.769). However, several low
      abundance bacteria were found to be significantly associated with the CO2
      affected group; very few of these species are known to metabolize CO2 or are
      associated with CO2-rich habitats. Although this study had limitations, on a
      broad scale, either the CO2 flood did not impact the microbial community
      composition of the target formation, or microbial communities in affected wells
      may have reverted back to pre-injection conditions over the ca. 40 years since
      the CO2-EOR.

PMID- 30101291
TI  - Corrigendum to: 'Analysis of aortic area/height ratio in patients with thoracic
      aortic aneurysm and Type A dissection' [Eur J Cardiothorac Surg 2018;
      doi:10.1093/ejcts/ezy110].

PMID- 30101292
TI  - Quantifying the growth of oncofertility.

PMID- 30101293
TI  - Energy balance affects pulsatile secretion of luteinizing hormone from the
      adenohypophesis and expression of neurokinin B in the hypothalamus of
      ovariectomized gilts.
AB  - The pubertal transition of gonadotropin secretion in pigs is metabolically gated.
      Kisspeptin (KISS1) and neurokinin B (NKB) are coexpressed in neurons within the
      arcuate nucleus of the hypothalamus (ARC) and are thought to play an important
      role in the integration of nutrition and metabolic state with the reproductive
      neuroendocrine axis. The hypothesis that circulating concentrations of
      luteinizing hormone (LH) and expression of KISS1 and tachykinin 3(TAC3, encodes
      NKB) in the ARC of female pigs are reduced with negative energy balance was
      tested using ovariectomized, prepubertal gilts fed to either gain or lose body
      weight. Restricted feeding of ovariectomized gilts caused a rapid and sustained
      metabolic response characterized by reduced concentrations of plasma urea
      nitrogen, insulin, leptin, and insulin-like growth factor-1 and elevated
      concentrations of free fatty acids. The secretory pattern of LH shifted from one
      of low amplitude to one of high amplitude, which caused overall circulating
      concentrations of LH to be greater in restricted gilts. Nutrient-restricted gilts
      had greater expression of follicle-stimulating hormone and gonadotropin-releasing
      hormone receptor, but not LH in the anterior pituitary gland. Expression of KISS1
      in the ARC was not affected by dietary treatment, but expression of TAC3 was
      greater in restricted gilts. These data are consistent with the idea that
      hypothalamic expression of KISS1 is correlated with the number of LH pulse in
      pig, and further indicate that amplitude of LH pulses may be regulated by NKB in
      the gilt.

PMID- 30101296
TI  - Salinity decreases Cd translocation by altering Cd speciation in the halophytic
      Cd-accumulator Carpobrotus rossii.
AB  - Background and Aims: Salt has been shown to affect Cd translocation and
      accumulation in plants but the associated mechanisms are unclear. This study
      examined the effects of salt type and concentration on Cd uptake, translocation
      and accumulation in Carpobrotus rossii. Methods: Plants were grown in nutrient
      solution with the same Cd concentration or Cd2+ activity in the presence of 25 mm
      NaNO3, 12.5 mm Na2SO4 or 25 mm NaCl for <=10 d. Plant growth and Cd uptake were
      measured and the accumulation of peptides and organic acids, and Cd speciation in
      plant tissues were analysed. Key Results: Salt addition decreased shoot Cd
      accumulation by >50 % due to decreased root-to-shoot translocation, irrespective
      of salt type. Synchrotron-based X-ray absorption spectroscopy revealed that,
      after 10 d, 61-94 % Cd was bound to S-containing ligands (Cd-S) in both roots and
      shoots, but its speciation was not affected by salt. In contrast, Cd in the xylem
      sap was present either as free Cd2+ or complexes with carboxyl groups (Cd-OH).
      When plants were exposed to Cd for <=24 h, 70 % of the Cd in the roots was
      present as Cd-OH rather than Cd-S. However, NaCl addition decreased the
      proportion of Cd-OH in the roots within 24 h by forming Cd-Cl complexes and
      increasing the proportion of Cd-S. This increase in Cd-S complexes by salt was
      not due to changes in glutathione and phytochelatin synthesis. Conclusions: Salt
      addition decreased shoot Cd accumulation by decreasing Cd root-to-shoot
      translocation due to the rapid formation of Cd-S complexes (low mobility) within
      the root, without changing the concentrations of glutathione and phytochelatins.

PMID- 30101295
TI  - A novel protocol for the preparation of active recombinant human pancreatic
      lipase from Escherichia coli.
AB  - An active recombinant human pancreatic lipase (recHPL) was successfully prepared
      for the first time from the Escherichia coli expression system using short Strep
      tag II (ST II). The recHPL-ST II was solubilized using 8 M urea from E.coli
      lysate and purified on a Strep-Tactin-Sepharose column. After refolding by
      stepwise dialyses in the presence of glycerol and Ca2+ for 2 days followed by gel
      filtration, 1.8-6 mg of active recHPL-ST II was obtained from 1 L of culture. The
      recHPL was non-glycosylated, but showed almost equal specific activity, pH
      dependency and time-dependent stability compared to those of native porcine
      pancreatic lipase (PPL) at 37 degrees C. However, the recHPL lost its lipolytic
      activity above 50 degrees C, showing a lower heat-stability than that of native
      PPL, which retained half its activity at this temperature.

PMID- 30101297
TI  - Genetic Simulation Resources and the GSR Certification Program.

PMID- 30101299
TI  - Xylo-oligosaccharides display a prebiotic activity when used to supplement wheat
      or corn-based diets for broilers.
AB  - It is now well established that exogenous beta-1,4-xylanases improve the
      nutritive value of wheat-based diets for poultry. Among other factors, the
      mechanism of action of exogenous enzymes may involve a microbial route resulting
      from the generation of prebiotic xylo-oligosaccharides (XOS) in the birds' gastro
      intestinal (GI) tract. In a series of three experiments, the effect of XOS on the
      performance of broilers fed wheat or corn-based diets was investigated. In
      experiment 1, birds receiving diets supplemented with XOS displayed an increased
      weight gain (P = 0.08). The capacity of XOS to improve the performance of animals
      during a longer trial (42 d) was investigated (Experiment 2). The data revealed
      that diet supplementation with XOS, tested at two incorporation rates (0.1 and 1
      g/kg), or with an exogenous beta-1,4-xylanase resulted in an increased nutritive
      value of the wheat-based diet. An improvement in animal performance was
      accompanied by a shift in the microbial populations colonizing the upper portions
      of the GI tract. XOS were also able to improve the performance of broilers fed a
      corn-based diet, although the effects were not apparent at incorporation rates of
      10 g/kg. Together these studies suggest that in some cases the capacity of beta
      1,4-xylanases to improve the nutritive value of wheat-based diets is more related
      to their ability to produce prebiotic XOS than to their ability to degrade
      arabinoxylans. The extremely low quantities of XOS used in this study also
      challenge the depiction of a prebiotic being a quantitatively fermented
      substrate. These data also bring into question the validity of the "cell wall"
      mechanism, as XOS elicited an effect with clearly no action on endosperm cell
      wall integrity and yet the performance effects noted were equivalent or superior
      to the added enzymes.

PMID- 30101300
TI  - Blood pressure, heart rate, and mortality in chronic obstructive pulmonary
      disease: the SUMMIT trial.
AB  - Aims: To characterize the relationship between blood pressure (BP) or heart rate
      and mortality and morbidity in chronic obstructive pulmonary disease (COPD).
      Methods and results: We performed post hoc analysis of baseline BP or heart rate
      and all-cause mortality and cardiovascular events in the SUMMIT trial. SUMMIT was
      a randomized double-blind outcome trial of 16 485 participants (65 +/- 8 years,
      75% male, and 47% active smokers) enrolled at 1368 sites in 43 countries.
      Participants with moderate COPD with or at risk for cardiovascular disease (CVD)
      were randomized to placebo, long-acting beta agonist, inhaled corticosteroid, or
      their combination. All-cause mortality increased in relation to high systolic
      [>=140 mmHg; hazard ratio (HR) 1.27, 95% confidence interval (CI) 1.12-1.45] or
      diastolic (>=90 mmHg; HR 1.35, 95% CI 1.14-1.59) BP and low systolic (<120 mmHg;
      HR 1.36, 95% CI 1.13-1.63) or diastolic (<80 mmHg; HR 1.15, 95% CI 1.00-1.32) BP.
      Higher heart rates (>=80 per minute; HR 1.39, 95% CI 1.21-1.60) and pulse
      pressures (>=80 mmHg; HR 1.39, 95% CI 1.07-1.80) were more linearly related to
      increases in all-cause mortality. The risks of cardiovascular events followed
      similar patterns to all-cause mortality. Similar findings were observed in
      subgroups of patients without established CVD. Conclusion: A 'U-shaped'
      relationship between BP and all-cause mortality and cardiovascular events exists
      in patients with COPD and heightened cardiovascular risk. A linear relationship
      exists between heart rate and all-cause mortality and cardiovascular events in
      this population. These findings extend the prognostic importance of BP to this
      growing group of patients and raise concerns that both high and low BP may pose
      health risks.

PMID- 30101301
TI  - Supraclavicular Brachial Plexus Approach for Excision of C8 Nerve Root
      Schwannoma: 3-Dimensional Operative Video.
AB  - Brachial plexus tumors are uncommon lesions in young adults. The majority of
      these are benign peripheral sheath tumors. In this 3-dimensional video, we
      present a case of a 19-yr-old female who presented to the neurosurgical
      outpatients with an anterior neck lump. It has been present for months, causing
      occasional numbness and paraesthesia in the distribution of the left ring finger.
      There was no objective weakness in finger flexion with normal long flexors
      reflexes. The cervical spine and supraclavicular brachial plexus were
      investigated with a magnetic resonance imaging (Gadolinium) scan (Figure 1). It
      demonstrated 30 * 20 * 20 mm lesion adjacent to the C8 nerve arising from the
      neural foramen, however, mostly occupying the space lateral to it. The patient
      was consented for resection of the tumor. This was done via the supraclavicular
      brachial plexus approach. The brachial plexus nerves were macroscopically
      demonstrated lateral to the anterior scalene muscle. The intraoperative
      electrophysiology was used to directly stimulate the nerves, which aided in
      accurate tracking during the dissection. The tumor was exposed after tracing the
      C8 nerve deep and medial to the anterior scalene muscle. It was resected down to
      the foramen, reaching the level of the epidural venous plexus, while C8 was
      spared. The patient recovered with no neurological deficit. The histopathology
      confirmed grade 1 schwannoma. Subsequently, there was no radiological follow-up
      performed. This case demonstrates the surgical dissection of supraclavicular
      brachial plexus in 3-dimensions while describing the unusual dissection medial to
      scalenus anterior muscle.

PMID- 30101298
TI  - Draft genome assembly of the invasive cane toad, Rhinella marina.
AB  - Background: The cane toad (Rhinella marina formerly Bufo marinus) is a species
      native to Central and South America that has spread across many regions of the
      globe. Cane toads are known for their rapid adaptation and deleterious impacts on
      native fauna in invaded regions. However, despite an iconic status, there are
      major gaps in our understanding of cane toad genetics. The availability of a
      genome would help to close these gaps and accelerate cane toad research.
      Findings: We report a draft genome assembly for R. marina, the first of its kind
      for the Bufonidae family. We used a combination of long-read Pacific Biosciences
      RS II and short-read Illumina HiSeq X sequencing to generate 359.5 Gb of raw
      sequence data. The final hybrid assembly of 31,392 scaffolds was 2.55 Gb in
      length with a scaffold N50 of 168 kb. BUSCO analysis revealed that the assembly
      included full length or partial fragments of 90.6% of tetrapod universal single
      copy orthologs (n = 3950), illustrating that the gene-containing regions have
      been well assembled. Annotation predicted 25,846 protein coding genes with
      similarity to known proteins in Swiss-Prot. Repeat sequences were estimated to
      account for 63.9% of the assembly. Conclusions: The R. marina draft genome
      assembly will be an invaluable resource that can be used to further probe the
      biology of this invasive species. Future analysis of the genome will provide
      insights into cane toad evolution and enrich our understanding of their interplay
      with the ecosystem at large.

PMID- 30101302
TI  - Uncoupling FT Protein Transport from its Function.

PMID- 30101303
TI  - ASGART: fast and parallel genome scale segmental duplications mapping.
AB  - Motivation: Segmental Duplications (SDs) are DNA fragments longer than 1 kbp,
      distributed within and between chromosomes and sharing more than 90% identity.
      Although they hold a significant role in genomic fluidity and adaptability, many
      key questions about their intrinsic characteristics and mutability remain
      unsolved due to the persistent difficulty of sequencing highly duplicated genomic
      regions. The recent development of long and linked-read NGS technologies will
      increase the need to search for SDs in genomes newly sequenced with these
      technics. The main limitation of SD analysis will soon be the availability of
      efficient detection software, to retrieve and compare SD genomic component
      between species or lineages. Results: In this paper, we present the open-source
      ASGART, 'A Segmental duplications Gathering And Refining Tool', developed to
      search for segmental duplications (SDs) in any assembled sequence. We have tested
      and benchmarked ASGART on five models organisms. Our results demonstrate ASGART's
      ability to extract SDs from any genome-wide sequence, regardless of genomic size
      or organizational complexity and quicker than any other software available.
      Availability and implementation: The online version of ASGART is available at
      http://asgart.irit.fr. The source code of ASGART is available both on the ASGART
      website and at https://github.com/delehef/asgart. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30101294
TI  - Progress and perspectives in plant sterol and plant stanol research.
AB  - Current evidence indicates that foods with added plant sterols or stanols can
      lower serum levels of low-density lipoprotein cholesterol. This review summarizes
      the recent findings and deliberations of 31 experts in the field who participated
      in a scientific meeting in Winnipeg, Canada, on the health effects of plant
      sterols and stanols. Participants discussed issues including, but not limited to,
      the health benefits of plant sterols and stanols beyond cholesterol lowering, the
      role of plant sterols and stanols as adjuncts to diet and drugs, and the
      challenges involved in measuring plant sterols and stanols in biological samples.
      Variations in interindividual responses to plant sterols and stanols, as well as
      the personalization of lipid-lowering therapies, were addressed. Finally, the
      clinical aspects and treatment of sitosterolemia were reviewed. Although plant
      sterols and stanols continue to offer an efficacious and convenient dietary
      approach to cholesterol management, long-term clinical trials investigating the
      endpoints of cardiovascular disease are still lacking.

PMID- 30101305
TI  - Developing and maintaining clinical decision support using clinical knowledge and
      machine learning: the case of order sets.
AB  - Development and maintenance of order sets is a knowledge-intensive task for off
      the-shelf machine-learning algorithms alone. We hypothesize that integrating
      clinical knowledge with machine learning can facilitate effective development and
      maintenance of order sets while promoting best practices in ordering. To this
      end, we simulated the revision of an "AM Lab Order Set" under 6 revision
      approaches. Revisions included changes in the order set content or default
      settings through 1) population statistics, 2) individualized prediction using
      machine learning, and 3) clinical knowledge. Revision criteria were determined
      using electronic health record (EHR) data from 2014 to 2015. Each revision's
      clinical appropriateness, workload from using the order set, and generalizability
      across time were evaluated using EHR data from 2016 and 2017. Our results suggest
      a potential order set revision approach that jointly leverages clinical knowledge
      and machine learning to improve usability while updating contents based on latest
      clinical knowledge and best practices.

PMID- 30101304
TI  - Immune system-mediated atherosclerosis caused by deficiency of long noncoding RNA
      MALAT1 in ApoE-/- mice.
AB  - Background: The immune system is considered a key driver of atherosclerosis, and
      beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) are
      implicated in immune control. We previously described that lncRNA MALAT1 is
      involved in cardiac innate immunity in a myocarditis model. Here, we investigated
      the impact of MALAT1 deficiency upon atherosclerosis development. Methods and
      Results: Heterozygous MALAT1-deficient ApoE-/- mice displayed massive immune
      system dysregulation and atherosclerosis within two months even when kept on
      normal diet. Aortic plaque area (p < 0.05) and aortic root plaque size (p <
      0.001) were increased in MALAT1-deficient vs. MALAT1-wildtype ApoE-/- mice. Serum
      levels of interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), and
      interleukin 6 (IL6) were elevated (p < 0.001) in MALAT1-deficient animals. MALAT1
      deficient bone marrow derived macrophages showed enhanced expression of TNF (p =
      0.001) and inducible NO synthase (NOS2) (p = 0.002), suppressed MMP9 (p < 0.001),
      and impaired phagocytic activity (p < 0.001) upon LPS stimulation. RNA-sequencing
      revealed grossly altered transcriptomes of MALAT1-deficient splenocytes already
      at baseline, with massive induction of IFN-gamma, TNF, NOS2, and granzyme B; CC
      and CXC chemokines and CCR8; and innate immunity genes IFIT1/3, IFITM1/3, ISG15.
      Multiple miRs were up to 45-fold upregulated. Further, selective ablation of the
      cytosolic part of the MALAT1 system only, the enzymatically MALAT1-derived
      mascRNA, resulted in massive induction of TNF (p = 0.004) and IL6 (p = 0.028) in
      macrophages. Northern analysis of post-MI patient vs. control PBMCs showed
      reduced (p = 0.005) mascRNA in the patients. CHART-enriched RNA-sequencing reads
      at the genomic loci of MALAT1 and neighbouring NEAT1 documented direct
      interaction between these lncRNA transcripts. Conclusion: The data suggest a
      molecular circuit involving the MALAT1-mascRNA system, interactions between
      MALAT1 and NEAT1, and key immune effector molecules, cumulatively impacting upon
      the development of atherosclerosis. It appears reasonable to look for therapeutic
      targets in this circuit and to screen for anomalies in the NEAT1-MALAT1 region in
      humans, too, as possible novel disease risk factors.

PMID- 30101307
TI  - Global importance of RNA secondary structures in protein coding sequences.
AB  - Motivation: The protein-coding sequences of messenger RNAs are the linear
      template for translation of the gene sequence into protein. Nevertheless, the RNA
      can also form secondary structures by intramolecular base-pairing. Results: We
      show that the nucleotide distribution within codons is biased in all taxa of life
      on a global scale. Thereby, RNA secondary structures that require base-pairing
      between the position 1 of a codon with the position 1 of an opposing codon (here
      named RNA secondary structure class c1) are under-represented. We conclude that
      this bias may result from the co-evolution of codon sequence and mRNA secondary
      structure, suggesting that RNA secondary structures are generally important in
      protein coding regions of mRNAs. The above result also implies that codon
      position 2 has a smaller influence on the amino acid choice than codon position
      1.

PMID- 30101306
TI  - Dynamics of Predation on Lygus hesperus (Hemiptera: Miridae) in Alfalfa Trap
      Cropped Organic Strawberry.
AB  - Alfalfa (Medicago sativa L.) (Fabales: Fabaceae) can be strategically planted as
      a trap crop for Lygus spp. in California's organic strawberry fields. Alfalfa has
      been shown to attract both Lygus spp. and, in turn, a Lygus-specific parasitoid,
      Peristenus relictus (Ruthe) (Hymenoptera: Braconidae). However, the impact of
      alfalfa trap-cropped strawberries on the Lygus spp. predator complex is unknown.
      Here we identify key predators of Lygus spp. found in organic strawberry. First,
      a general survey was conducted at an organic, non-trap cropped strawberry farm,
      to quantify predator abundance and to qualitatively assess their feeding activity
      on Lygus spp. We identified the 11 most abundant predator taxa present and, by
      using a Lygus-specific PCR assay, determined that about 18% of the insects and
      spiders contained Lygus spp. remains in their guts. We then conducted a study to
      examine alfalfa's role in conserving the most relevant predators in trap-cropped
      organic strawberries. Specifically, we quantified predator abundance and
      qualitatively measured predator feeding activity (by gut analysis) on Lygus spp.
      collected in strawberry plots either lacking or containing an alfalfa trap crop.
      Data revealed that some predator taxa, including the numerically dominant
      predator, Orius tristicolor (White) (Hemiptera: Anthocoridae), aggregated in
      alfalfa trap crops. The gut content analyses revealed that insect and spider
      predators collected from the alfalfa trap crop had a significantly higher
      proportion of their population containing Lygus spp. remains than those collected
      from nearby rows of strawberries. These results suggest that alfalfa trap
      cropping might be a useful tactic for conserving the biological control services
      of generalist predators in organically grown strawberries in California.

PMID- 30101308
TI  - Re-exploration for bleeding associated with increased incidence of the need for
      reintervention after coronary artery bypass graft surgery.
AB  - OBJECTIVES: Re-exploration for bleeding after cardiac surgery increases the risk
      of other severe postoperative complications and early mortality. Patients re
      explored for bleeding after coronary artery bypass grafting are potentially
      subject to threats to graft patency. Our goal was to assess the effects of re
      exploration for bleeding regarding the incidence of coronary angiographies, the
      need for coronary reintervention and mortality during long-term follow-up.
      METHODS: Within the SWEDEHEART registry, all isolated coronary artery bypass
      operations with a single internal mammary artery and saphenous vein graft in
      patients aged 40-80 between the years 2005 and 2015 were identified. Incidences
      of coronary angiography and the subsequent need for coronary reintervention were
      recorded, and multivariable adjusted hazard ratios (HRs) were calculated.
      RESULTS: The study cohort consisted of 27 957 patients, and the mean follow-up
      time was 6.5 +/- 3.1 years. The incidence of re-exploration for bleeding was 3.8%
      (n = 1071). The cumulative incidence [95% confidence interval (CI)] of a
      clinically occurring coronary angiography within 1 year after surgery was 7.8%
      (6.3-9.7) in re-explored and 4.8% (4.6-5.1) in non-re-explored patients, and the
      adjusted HR was 1.64 (1.31-2.06), (P < 0.001). The cumulative incidence of the
      need for coronary reintervention within 1 year (95% CI) was 4.9% (3.7-6.4) in re
      explored and 2.6% (2.4-2.8) in non-re-explored patients, and the adjusted HR was
      1.91 (1.43-2.56). No difference in incidence or hazard ratio was observed beyond
      the first year. Mortality rate was increased within but not beyond 90 days after
      surgery. CONCLUSIONS: Re-exploration for bleeding is associated with an increased
      risk for the need of repeat coronary reintervention during the first year after
      coronary artery bypass surgery.

PMID- 30101309
TI  - Container-based bioinformatics with Pachyderm.
AB  - Motivation: Computational biologists face many challenges related to data size,
      and they need to manage complicated analyses often including multiple stages and
      multiple tools, all of which must be deployed to modern infrastructures. To
      address these challenges and maintain reproducibility of results, researchers
      need (i) a reliable way to run processing stages in any computational
      environment, (ii) a well-defined way to orchestrate those processing stages, and
      (iii) a data management layer that tracks data as it moves through the processing
      pipeline. Results: Pachyderm is an open-source workflow system and data
      management framework that fulfills these needs by creating a data pipelining and
      data versioning layer on top of projects from the container ecosystem, having
      Kubernetes as the backbone for container orchestration. We adapted Pachyderm and
      demonstrated its attractive properties in bioinformatics. A Helm Chart was
      created so that researchers can use Pachyderm in multiple scenarios. The
      Pachyderm File System was extended to support block storage. A wrapper for
      initiating Pachyderm on cloud-agnostic virtual infrastructures was created. The
      benefits of Pachyderm are illustrated via a large metabolomics workflow,
      demonstrating that Pachyderm enables efficient and sustainable data science
      workflows while maintaining reproducibility and scalability. Availability:
      Pachyderm is available from https://github.com/pachyderm/pachyderm. The Pachyderm
      Helm Chart is available from
      https://github.com/kubernetes/charts/tree/master/stable/pachyderm. Pachydermis
      available out-of-the-box from the PhenoMeNalVRE(https://github.com/phnmnl/KubeNow
      plugin) and general Kubernetes environments instantiated via KubeNow. The code of
      the workflow used for the analysis is available on GitHub
      (https://github.com/pharmbio/LC-MS-Pachyderm). Supplementary Information:
      Supplementary data is available at Bioinformatics online.

PMID- 30101310
TI  - Linkage disequilibrium maps to guide contig ordering for genome assembly.
AB  - Motivation: Efforts to establish reference genome sequences by de novo sequence
      assembly have to address the difficulty of linking relatively short sequence
      contigs to form much larger chromosome assemblies. Efficient strategies are
      required to span gaps and establish contig order and relative orientation. We
      consider here the use of linkage disequilibrium (LD) maps of sequenced contigs
      and the utility of LD for ordering, orienting and positioning linked sequences.
      LD maps are readily constructed from population data and have at least an order
      of magnitude higher resolution than linkage maps providing the potential to
      resolve difficult areas in assemblies. We empirically evaluate a linkage
      disequilibrium map-based method using single nucleotide polymorphism genotype
      data in a 216 kilobase region of human 6p21.3 from which three shorter contigs
      are formed. Results: LD map length is most informative about the correct order
      and orientation and is suggested by the shortest LD map where the residual error
      variance is close to one. For regions in strong LD this method may be less
      informative for correcting inverted contigs than for identifying correct contig
      orders. For positioning two contigs in linkage disequilibrium with each other the
      inter-contig distances may be roughly estimated by this method. Availability: The
      LDMAP program is written in C for a linux platform and is available at
      https://www.soton.ac.uk/genomicinformatics/research/ld.page. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30101311
TI  - Systems Science in Rehabilitation Practice Realized.

PMID- 30101312
TI  - Early childhood antibiotics use and autism spectrum disorders: a population-based
      cohort study.
AB  - Background: Changes in microbiota composition as a result of antibiotics use in
      early life has been proposed as a possible contributor in the aetiology of autism
      spectrum disorders (ASD). We aimed to examine the association between early life
      antibiotic exposure and risk of ASD. Methods: This was a population-based cohort
      study which included all live births in Manitoba, Canada, between 1 April 1998
      and 31 March 2016. We used administrative health data from the Manitoba
      Population Research Data Repository. Exposure was defined as having filled one or
      more antibiotic prescription during the first year of life. The main outcome was
      ASD diagnosis. Cox proportional hazards regression models were used to estimate
      the risk of developing ASD in the overall population and in a sibling cohort.
      Results: Of all subjects in the cohort (n = 214 834), 94 024 (43.8%) filled an
      antibiotic prescription during the first year of life. During follow-up, 2965
      children received an ASD diagnosis. Compared with children who did not use
      antibiotics during the first year of life, those who received antibiotics had a
      reduced risk of ASD [adjusted hazardz ratio (HR) 0.91, 95% confidence interval
      (CI) 0.84-0.99). Number of treatment courses and cumulative duration of
      antibiotic exposure were not associated with ASD. In the sibling-controlled
      analysis, early life antibiotic exposure was not associated with ASD (adjusted HR
      1.03, 95% CI 0.86-1.23). Conclusions: Our findings suggested no clinically
      significant association between early life antibiotics exposure and risk of
      autism spectrum disorders, and should provide reassurance to concerned
      prescribers and parents.

PMID- 30101313
TI  - Heart Team decision making and long-term outcomes for 1000 consecutive cases of
      coronary artery disease.
AB  - OBJECTIVES: The Heart Team has been recommended as standard care for patients
      with coronary artery disease (CAD). However, little is known about the real
      benefits, potential treatment delays and late outcomes of this approach. Our goal
      was to determine the safety and feasibility of multidisciplinary Heart Team
      decision making for patients with CAD. METHODS: We retrospectively assessed 1000
      consecutive cases discussed by the Heart Team between November 2010 and January
      2012. We assessed (i) time intervals between different care steps involving the
      Heart Team; (ii) the distribution of patients according to the complexity of
      their CAD; and (iii) the 5-year survival as estimated from Kaplan-Meier curves.
      RESULTS: Of 1000 case discussions, 40 were repeat cases, resulting in 960 unique
      cases. The mean age was 65 years, 73% were men, and 29% had diabetes. Native
      vessel disease was present in 86.4%, of which 69% had simple 1-vessel disease
      (1VD) or 2-vessel disease (2VD), and 31% had complex left main (LM) or 3-vessel
      disease (3VD). The time interval between referral by a community hospital and
      final treatment was less than 6 weeks for 90% of cases. Treatment decisions were
      delayed in 35% of cases due to a need for additional diagnostic information. For
      simple 1- or 2VD with or without proximal left anterior descending artery
      involvement, treatment was medical therapy in 6% and 12%, respectively;
      percutaneous coronary intervention (PCI) in 88% and 85%, respectively; and
      coronary artery bypass grafting (CABG) in 6% and 3%, respectively. For 3VD
      disease, treatment was equally split between CABG and PCI (46% for both). PCI was
      preferred for isolated LM or LM with 1VD (81% vs CABG 16%), whereas CABG was
      preferred in LM with 2- or 3VD (71% vs PCI 19%). The 5-year mortality rate was
      16% for 1- or 2VD, 17% for 3VD, 3% for isolated LM or with 1VD and 27% for LM
      with 2- or 3VD. CONCLUSIONS: In this single-centre analysis, the Heart Team
      approach was feasible, with decision making and treatment by the Heart Team
      following within a short time after referral. However, the timing of treatment
      could be further optimized if adequate information and imaging were available at
      the time of the Heart Team meeting. The final treatment recommendation by the
      Heart Team was largely in accordance with clinical guidelines.

PMID- 30101314
TI  - Investigating the genetic determination of clutch traits in laying hens.
AB  - Clutch traits were proposed as a more detailed description of egg-laying patterns
      than simple total egg production. In this study, egg production of 23,809 Rhode
      Island Red (RIR) and 22,210 White Leghorn (WL) hens was described in terms of
      number of clutches, average and maximum clutch size, age at first egg, total
      saleable egg production, and percentage of egg defects. Genetic parameters were
      estimated using a six-trait animal model. Of the phenotyped birds, 1433 RIR hens
      and 1515 WL hens were genotyped with line specific 50K Affymetrix Axiom single
      nucleotide polymorphism chips to perform genome-wide association analyses.
      Moderate heritabilities were estimated for clutch traits of 0.20 to 0.42 in the
      RIR line and 0.29 to 0.41 in the WL line. Average and maximum clutch size was
      positively genetically correlated with total saleable egg number in both lines.
      Genome-wide association analysis identified seven regions that were associated
      with egg production in the RIR line and 12 regions in the WL line. The regions
      identified were line and trait specific, except for one region on chromosome 6
      from 28 to 29 Mb that influenced number of clutches and maximum and average
      clutch size in WL hens. Regions associated with egg production identified here
      overlapped with 260 genes, with some strong positional candidates based on gene
      ontology including WASH1, which is involved in oocyte maturation, NPVF, involved
      in regulation of follicle-stimulating hormone secretion, and FOXO3, involved in
      oocyte maturation and ovulation from the ovarian follicle. Confirmation of the
      role of these genes in regulation of egg production pattern will require further
      studies.

PMID- 30101315
TI  - Prognostic utility of HPV specific testing in addition to p16
      immunohistochemistry in oropharyngeal squamous cell carcinoma.

PMID- 30101316
TI  - Processing of big heterogeneous genomic datasets for tertiary analysis of Next
      Generation Sequencing data.
AB  - Motivation: We previously proposed a paradigm shift in genomic data management,
      based on the Genomic Data Model (GDM) for mediating existing data formats and on
      the GenoMetric Query Language (GMQL) for supporting, at a high level of
      abstraction, data extraction and the most common data-driven computations
      required by tertiary data analysis of Next Generation Sequencing datasets. Here,
      we present a new GMQL-based system with enhanced accessibility, portability,
      scalability and performance. Results: The new system has a well-designed modular
      architecture featuring: i) an intermediate representation supporting many
      different implementations (including Spark, Flink, and SciDB); ii) a high-level
      technology-independent repository abstraction, supporting different repository
      technologies (e.g., local file system, Hadoop File System, database, or others);
      iii) several system interfaces, including a user-friendly Web-based interface, a
      Web Service interface, and a programmatic interface for Python language.
      Biological use case examples, using public ENCODE, Roadmap Epigenomics and TCGA
      datasets, demonstrate the relevance of our work. Availability: The GMQL system is
      freely available for non-commercial use as open source project at:
      http://www.bioinformatics.deib.polimi.it/GMQLsystem/.

PMID- 30101317
TI  - Durability of tissue-engineered bovine pericardium (CardioCel(r)) for a minimum
      of 24 months when used for the repair of congenital heart defects.
AB  - OBJECTIVES: This study aims to assess the performance of tissue-engineered bovine
      pericardium (CardioCel(r)) at 24 months and beyond when used for the repair of
      congenital heart defects. METHODS: Between October 2012 and November 2014,
      CardioCel was implanted in 135 patients (140 procedures and 195 implants).
      Applications included the closure of septal defects (98, 50.3%), repair of
      pulmonary arteries (63, 32.3%), intra-atrial/intraventricular baffles (10, 5.1%),
      repair of systemic arteries (15, 7.7%), valve repair (5, 2.6%), repair of
      systemic veins (3, 1.5%) and Fontan operation (1, 0.5%). There were 19 (13.6%)
      procedures performed in neonates, 77 (55%) in infants and 44 (31.4%) in children
      older than 365 days. RESULTS: Eight patients (n = 135, 5.9%) required
      reintervention in 12 instances (n = 195, 6.2%, 6 catheters and 6 surgical). There
      was no echocardiographic or radiological evidence of calcification in any
      patient. Ten of the reinterventions (83%) occurred within the first 12 months.
      All the reinterventions occurred within 36 months. Freedom from reintervention at
      both 12 and 24 months was 95% [confidence interval (CI) 91-97] and at 36 months
      was 94% (CI 89-97). There was no statistical difference in freedom from
      reintervention when stratified by age or patch position. CONCLUSIONS: At 24
      months and beyond the follow-up, the performance of CardioCel remains acceptable
      with good haemodynamic performance. There was no echocardiographic or
      radiological evidence of calcification in any patient. CardioCel performs
      comparably in systemic and pulmonary circulations.

PMID- 30101319
TI  - Eculizumab for catastrophic antiphospholipid syndrome-a case report and
      literature review.

PMID- 30101318
TI  - PlaNC-TE: a comprehensive knowledgebase of non-coding RNAs and transposable
      elements in plants.
AB  - Transposable elements (TEs) play an essential role in the genetic variability of
      eukaryotic species. In plants, they may comprise up to 90% of the total genome.
      Non-coding RNAs (ncRNAs) are known to control gene expression and regulation.
      Although the relationship between ncRNAs and TEs is known, obtaining the
      organized data for sequenced genomes is not straightforward. In this study, we
      describe the PlaNC-TE (http://planc-te.cp.utfpr.edu.br), a user-friendly portal
      harboring a knowledgebase created by integrating and analysing plant ncRNA-TE
      data. We identified a total of 14 350 overlaps between ncRNAs and TEs in 40 plant
      genomes. The database allows users to browse, search and download all ncRNA and
      TE data analysed. Overall, PlaNC-TE not only organizes data and provides insights
      about the relationship between ncRNA and TEs in plants but also helps improve
      genome annotation strategies. Moreover, this is the first database to provide
      resources to broadly investigate functions and mechanisms involving TEs and
      ncRNAs in plants.

PMID- 30101320
TI  - Parent Training for Feeding Problems in Children With Autism Spectrum Disorder:
      Initial Randomized Trial.
AB  - Objective: Many children with autism spectrum disorder (ASD) have feeding and
      mealtime problems. To address these, we conducted a pilot randomized trial of a
      new 11-session, individually delivered parent training program that integrated
      behavioral strategies and nutritional guidance (PT-F). Methods: Forty-two young
      children (age: 2 to 7-11 years) with ASD and feeding problems were assigned to 11
      sessions of PT-F intervention over 20 weeks or a waitlist control. Outcomes
      included attendance, parent satisfaction, therapist fidelity, and preliminary
      assessments of child and parent outcomes. Results: Of the 21 PT-F families,
      attendance was high (85%) as was parent satisfaction (94% would recommend to
      others). Treatment fidelity was also high (97%-therapist integrity; 94%-parent
      adherence). Compared with waitlist, children whose parents participated in PT-F
      showed significantly greater reductions on the two parent-completed primary
      outcomes (Brief Autism Mealtime Behavior Inventory-Revised; Twald = -2.79; p =
      .003; About Your Child's Eating; Twald = -3.58; p = .001). On the independent
      evaluator-completed secondary eating outcome, the Clinical Global Impression
      Improvement, 48.8% of the participants in PT-F were rated as "responders"
      compared with 0% in waitlist (p = .006). General child disruptive behavior
      outcomes decreased more in PT-F but not significantly. Parent outcomes of
      caregiver stress showed nonsignificant trends favoring PT-F with moderate to
      small effect sizes. Conclusions: This trial provides evidence for feasibility,
      satisfaction, and fidelity of implementation of PT-F for feeding problems in
      young children with ASD. Feeding outcomes also appeared favorable and lends
      support for conducting a larger efficacy trial.

PMID- 30101321
TI  - GlycanAnalyzer: Software for Automated Interpretation of N-Glycan Profiles after
      Exoglycosidase Digestions.
AB  - Summary: Many eukaryotic proteins are modified by N-glycans. Liquid
      chromatography (ultra-performance -UPLC and high-performance - HPLC) coupled with
      mass spectrometry (MS) is conventionally used to characterize N-glycan
      structures. Software can automatically assign glycan structures by matching their
      observed retention times and masses with standardized values in reference
      databases. However, more precise confirmation of N-glycan structures can be
      derived using exoglycosidases, enzymes that remove specific monosaccharides from
      glycans. Exoglycosidase removal of monosaccharides results in signature peak
      shifts, in both UPLC and MS1, yielding an effective way to verify N-glycan
      structure with high detail (down to the position and isomeric linkage of each
      monosaccharide). Because manual interpretation of exoglycosidase data is complex
      and time consuming, we developed GlycanAnalyzer, a web application that pattern
      matches N-glycan peak shifts following exoglycosidase digestion and automates
      structure assignments. GlycanAnalyzer significantly improves assignment accuracy
      over other auto-assignment methods on tests with a monoclonal antibody and four
      glycan standards (100% vs. 82% for the next best software). By automating data
      interpretation, GlycanAnalyzer enables the easier use of exoglycosidases to
      precisely define N-glycan structure. Availability: http://glycananalyzer.neb.com
      . Datasets available online. Supplementary information: Supplementary info is
      available at Bioinformatics online.

PMID- 30101323
TI  - Members of the GH3 Family of Proteins Conjugate 2,4-D and Dicamba with Aspartate
      and Glutamate.
AB  - Auxin homeostasis is a highly regulated process that must be maintained to allow
      auxin to exert critical growth and developmental controls. Auxin conjugase and
      hydrolase family proteins play important roles in auxin homeostasis through means
      of storage, activation, inactivation, response inhibition and degradation of
      auxins in plants. We systematically evaluated 60 GRETCHEN HAGEN3 (GH3) proteins
      from diverse plant species for amino acid conjugation activity with the known
      substrates jasmonic acid (JA), IAA and 4-hydroxybenzoate (4-HBA). While our
      results largely confirm that Group II conjugases prefer IAA, we observed no clear
      substrate preference among Group III proteins, and only three of 11 Group I
      proteins showed the expected preference for JA, indicating that sequence
      similarity does not always predict substrate specificity. Such a sequence
      substrate relationship held true when sequence similarity at the acyl acid
      binding site was used for grouping. Several GH3 proteins could catalyze formation
      of the potentially degradation-destined aspartate (Asp) and glutamate (Glu)
      conjugates of IAA and the synthetic auxins 2,4-D and dicamba. We found that 2,4-D
      Asp/Glu conjugates, but not dicamba and IAA conjugates, were hydrolyzed in
      Arabidopsis and soybean by AtILL5- and AtIAR3-like amidohydrolases, releasing
      free 2,4-D in plant cells when conjugates were exogenously applied to seedlings.
      Dicamba-Asp or dicamba-Glu conjugates were not hydrolyzed in vivo in infiltrated
      plants nor in vitro with recombinant amidohydrolases. These findings could open
      the door for exploration of a dicamba herbicide tolerance strategy through
      conjugation.

PMID- 30101325
TI  - Erratum for Farebrother J et al. Effects of iodized salt and iodine supplements
      on prenatal and postnatal growth: a systematic review. Adv Nutr 2018;9(3):219-37.

PMID- 30101322
TI  - The chromosome-level genome assemblies of two rattans (Calamus simplicifolius and
      Daemonorops jenkinsiana).
AB  - Background: Calamus simplicifolius and Daemonorops jenkinsiana are two
      representative rattans, the most significant material sources for the rattan
      industry. However, the lack of reference genome sequences is a major obstacle for
      basic and applied biology on rattan. Findings: We produced two chromosome-level
      genome assemblies of C. simplicifolius and D. jenkinsiana using Illumina, Pacific
      Biosciences, and Hi-C sequencing data. A total of ~730 Gb and ~682 Gb of raw data
      covered the predicted genome lengths (~1.98 Gb of C. simplicifolius and ~1.61 Gb
      of D. jenkinsiana) to ~372 * and ~426 * read depths, respectively. The two de
      novo genome assemblies, ~1.94 Gb and ~1.58 Gb, were generated with scaffold N50s
      of ~160 Mb and ~119 Mb in C. simplicifolius and D. jenkinsiana, respectively. The
      C. simplicifolius and D. jenkinsiana genomes were predicted to harbor  51,235 and
      53,342 intact protein-coding gene models, respectively. Benchmarking Universal
      Single-Copy Orthologs evaluation demonstrated that genome completeness reached
      96.4% and 91.3% in the C. simplicifolius and D. jenkinsiana genomes,
      respectively. Genome evolution showed that four Arecaceae plants clustered
      together, and the divergence time between the two rattans was ~19.3 million years
      ago. Additionally, we identified 193 and 172 genes involved in the lignin
      biosynthesis pathway in the C. simplicifolius and D. jenkinsiana genomes,
      respectively. Conclusions: We present the first de novo assemblies of two rattan
      genomes (C. simplicifolius and D. jenkinsiana). These data will not only provide
      a fundamental resource for functional genomics, particularly in promoting
      germplasm utilization for breeding, but also serve as reference genomes for
      comparative studies between and among different species.

PMID- 30101324
TI  - Water absorption and dripping of chicken breast and carcasses during pre-cooling
      in an industrial system.
AB  - This study aimed to evaluate the parameters that influence the water absorption
      and drip of chicken carcasses due to the processing and pre-cooling of the meat
      in an industrial chiller. A total of 1,179 chickens were sampled during
      industrial processing to evaluate the influence of variables, validate the
      parameters, and conduct histological analysis. The best parameters for
      guaranteeing absorption levels and drip tests within acceptable limits on chicken
      carcasses were total residence time of 60 min (in the pre-chiller, chiller 1, and
      chiller 2); air pressure of chillers at 0.5 bar; the abdominal opening of
      carcasses at a maximum of 2 cm. These parameters did not influence the protein
      content, moisture/protein ratio, pH, or lipid content. The validation of the
      parameters and the histological analysis performed after each cooling stage
      showed that the most significant structural changes occurred in the pre-chiller,
      where the temperature of carcasses and water was higher, which contributes to
      greater absorption.

PMID- 30101326
TI  - Association of metabolic syndrome with non-thromboembolic adverse cardiac
      outcomes in patients with atrial fibrillation.
AB  - Aims: Evidence suggests an excess risk of non-thromboembolic major adverse
      cardiac events (MACE) associated with atrial fibrillation (AF), particularly in
      individuals free of overt coronary artery disease (CAD). Metabolic syndrome
      (MetS) increases cardiovascular risk in the general population, but less is known
      how it influences outcomes in AF patients. We aimed to assess whether MetS
      affects the risk of MACE in AF patients without overt CAD. Methods and results:
      This prospective, observational study enrolled 843 AF patients (mean-age, 62.5 +/
      12.1 years, 38.6% female) without overt CAD. Metabolic syndrome was defined
      according to the National Cholesterol Education Program. The 5-year composite
      MACE included myocardial infarction (MI), coronary revascularization, and cardiac
      death. Metabolic syndrome was present in 302 (35.8%) patients. At 5-year follow
      up, 118 (14.0%) patients experienced MACE (2.80%/year). Metabolic syndrome
      conferred a multivariable adjusted hazard ratio (aHR) of 1.98 for MACE [95%
      confidence interval (CI), 1.23-3.16; P = 0.004], and for individual outcomes: MI
      (aHR, 2.00; 95% CI, 1.69-5.11; P < 0.001), revascularization (aHR, 2.33; 95% CI,
      1.40-3.87; P = 0.001), and cardiac death (aHR, 2.59; 95% CI, 1.25-5.33; P =
      0.011). Following the propensity score (PS)-adjustment for MetS, the association
      between MetS and MACE (PS-aHR, 1.87; 95% CI, 1.21-3.01; P = 0.012), MI (PS-aHR,
      1.72; 95% CI, 1.54-5.00; P = 0.008), revascularization (PS-aHR, 2.18; 95% CI,
      1.69-3.11; P = 0.015), and cardiac death (PS-aHR, 2.27; 95% CI, 1.14-5.11; P =
      0.023) remained significant. Conclusion: Metabolic syndrome is common in AF
      patients without overt CAD, and confers an independent, increased risk of MACE,
      including MI, coronary revascularization, and cardiac death. Given its prognostic
      implications, prevention and treatment of MetS may reduce the burden of non
      thromboembolic complications in AF.

PMID- 30101327
TI  - Microsurgical Clip Placement for a Giant Anterior Communicating Artery Aneurysm
      With Intraluminal Thrombus: 2-Dimensional Operative Video.
AB  - Giant brain aneurysms account for approximately 5% of all intracranial aneurysms.
      Although treatment modalities can vary widely, none is ideal for every patient.
      Endovascular treatment is usually preferred, especially when the large size of
      the aneurysm limits visualization of the brain parenchyma and parent vessels that
      arise from the aneurysm, making surgical clip placement across the neck a
      difficult task. However, despite the higher chances of morbidity, microsurgery is
      an effective treatment modality due to lower recurrence rates. Surgically, a wide
      neck, calcifications, or atheroma are complicating factors to be considered while
      planning the best treatment. Thus, with an appropriate case selection, a
      favorable outcome is feasible in most cases. Here, we present the case of a 27-yr
      old female who presented with a severe headache for 7 mo and 3 mo of progressive
      left temporal vision loss, which was confirmed by visual field perimetry using
      the Humphrey visual field analyzer. Magnetic resonance angiography and digital
      subtraction cerebral angiography showed an anterior communicating artery complex
      inferiorly and medially oriented aneurysm measuring 25.4 * 16.5 mm, with a 3 mm
      neck. It was fed by the right A1, associated with a hypoplastic left A1,
      incorporating the proximal right and left A2 segments, with an intraluminal
      thrombus and causing mass effect on the optic chiasm and hypothalamus. This video
      demonstrates the microsurgical steps required to perform this operation, through
      a right orbitozygomatic craniotomy. At a 3-mo follow-up, the patient was
      neurological intact without complaints. The patient signed the Institutional
      Consent Form, which allows the use of his/her images and videos for any type of
      medical publications in conferences and/or scientific articles.

PMID- 30101328
TI  - Trajectories of body fatness from age 5 to 60 y and plasma biomarker
      concentrations of the insulin-insulin-like growth factor system.
AB  - Background: A major pathway through which obesity increases the risk of
      cardiometabolic diseases and cancer is by inducing hormonal and metabolic
      abnormalities, including hyperinsulinemia and altered insulin-like growth factor
      (IGF) signaling. However, little is known about the influence of lifetime
      adiposity on the relevant biomarkers. Objective: The aim of this study was to
      examine associations of trajectories of body fatness with plasma biomarker
      concentrations of the insulin-IGF system in 2 large prospective cohorts of US men
      and women. Design: Associations between trajectories of body fatness and
      concentrations of plasma C-peptide, IGF-I, IGF-binding protein (IGFBP) 1, IGFBP
      3, and the IGF-I-to-IGFBP-3 molar ratio was examined in 9386 women of the Nurses'
      Health Study and 3941 men of the Health Professionals Follow-Up Study. Group
      based trajectory modeling was used to create trajectory groups on the basis of
      self-reported somatotype data at ages 5, 10, 20, 30, and 40 y and body mass index
      (BMI) at ages 45, 50, 55, and 60 y. We used multivariate linear regression models
      to examine the associations of trajectories with biomarker concentrations.
      Results: Five trajectories of body fatness were identified: "lean-stable," "lean
      moderate increase," "lean-marked increase," "medium-stable/increase," and "medium
      marked increase." Compared with the lean-stable group, the lean-marked increase
      and medium-marked increase groups had significantly higher concentrations of C
      peptide (percentage difference-women: 44% and 73%; men: 27% and 51%) and lower
      concentrations of IGFBP-1 (women: -61% and -78%; men: -47% and -65%). Adjustment
      for current BMI attenuated the association to null for the medium-marked increase
      group, but the lean-marked increase group still had modestly higher
      concentrations of C-peptide (women: 10%; men: 6%) and lower concentrations of
      IGFBP-1 (women: -18%; men: -21%) than the lean-stable group. Conclusions:
      Adiposity across the life span was associated with higher C-peptide and lower
      IGFBP-1 concentrations in adulthood. The associations were largely driven by
      attained adiposity and, to a lesser extent, weight gain in early-middle
      adulthood. This trial was registered at www.clinicaltrials.gov as NCT03419455.

PMID- 30101329
TI  - Sleep, nutrition, and physical activity interventions to prevent obesity in
      infancy: follow-up of the Prevention of Overweight in Infancy (POI) randomized
      controlled trial at ages 3.5 and 5 y.
AB  - Background: Our Prevention of Overweight in Infancy (POI) study suggested that a
      brief sleep intervention in infancy reduced the risk of obesity at age 2 y. In
      contrast, we observed no benefit from the nutrition and activity intervention.
      Objective: The objective of the study was to determine how these interventions
      influenced growth at ages 3.5 and 5 y compared with usual care (Control). Design:
      A follow-up of a parallel, 4-arm, single-blind, 2-y, randomized controlled trial
      in 802 women (86% European, 48% primiparous) recruited in pregnancy (58% response
      rate) was undertaken. All groups received standard Well-Child care with
      additional support for 3 intervention groups: FAB (promotion of breastfeeding,
      healthy eating, physical activity: 8 contacts, antenatal, 18 mo); Sleep
      (prevention of sleep problems: antenatal, 3 wk); Combination (both
      interventions). Follow-up measures were collected by staff blinded to group
      allocation. The primary outcome was child body mass index (BMI) z score, and
      secondary outcomes were prevalence of obesity (BMI >=95th percentile), self
      regulation (psychological measures), sleep, physical activity (accelerometry,
      questionnaires), and dietary intake (food-frequency questionnaire). Analyses were
      conducted through the use of multiple imputation. Results: Retention was 77% at
      age 3.5 y and 69% at age 5 y. Children in the FAB group had significantly higher
      BMI z scores than did Controls at age 5 y (adjusted difference: 0.25; 95% CI:
      0.04, 0.47) but not at age 3.5 y (0.15; 95% CI: -0.04, 0.34). Children who
      received the Sleep intervention (Sleep and Combination groups) had significantly
      lower BMI z scores at age 3.5 y (-0.24; 95% CI: -0.38, -0.10) and at age 5 y (
      0.23; 95% CI: -0.38, -0.07) than children who did not (Control and FAB groups).
      Conclusions: A conventional intervention had unexpected adverse long-term weight
      outcomes, whereas positive outcomes from a less conventional sleep intervention
      remained promising at age 5 y. More intensive or extended sleep intervention
      might have larger or longer-lasting effects and should be investigated. This
      trial was registered at clinicaltrials.gov as NCT00892983.

PMID- 30101331
TI  - Reply to "Dietary glucosinolates and risk of type 2 diabetes in 3 prospective
      cohort studies".

PMID- 30101330
TI  - Breastfeeding to 12 mo and beyond: nutrition outcomes at 3 to 5 y of age.
AB  - Background: Little is known about nutrition outcomes in preschoolers associated
      with breastfeeding duration beyond 12 mo of age. Objective: The aim was to
      examine the association between total breastfeeding duration and nutrition
      outcomes at 3 to 5 y of age. Design: A cross-sectional study in healthy children,
      ages 3-5 y, recruited from 9 primary care practices in Toronto was conducted
      through the TARGet Kids! (The Applied Research Group for Kids) research network.
      Parents completed standardized surveys, including the Nutrition Screening for
      Every Preschooler (NutriSTEP) used to assess nutrition risk. Results: A total of
      2987 children were included. Ninety-two percent of children were breastfed, and
      the mean +/- SD breastfeeding duration was 11.4 +/- 8.4 mo. The prevalence of
      nutrition risk (score >20) was 17.0%. We examined breastfeeding duration as a
      continuous variable. With the use of restricted cubic spline modeling, we
      confirmed a nonlinear relation between breastfeeding duration and NutriSTEP
      score, dietary intake and eating behavior subscores, and sugar-sweetened beverage
      and sweet-savory snack consumption. Segmented linear regression was used to
      examine this nonlinear relation in a piecewise approach. We found a decreasing
      trend in NutriSTEP score for children who were breastfed for 0-6 mo (beta = 
      0.14; 95% CI: -0.29, 0.004), a significant decrease in NutriSTEP score for
      children breastfed for 6-12 mo (beta = -0.20; 95% CI: -0.33, -0.07), and no
      significant change after 12 mo (beta = 0.09; 95% CI: -0.07, 0.24) and beyond. The
      mean +/- SD NutriSTEP scores were 17.1 +/- 7.4 for no breastfeeding, 15.9 +/- 6.5
      for breastfeeding >0-6 mo, 13.9 +/- 6.2 for >6-12 mo, 13.7 +/- 6.3 for >12-18 mo,
      14.6 +/- 6.7 for >18-24 mo, and 14.3 +/- 6.8 for >24-36 mo. Conclusions:
      Breastfeeding for <=12 mo was associated with decreased nutrition risk and
      healthier eating behaviors and dietary intake at 3-5 y of age. We found
      insufficient evidence of additional benefit for breastfeeding beyond 12 mo of
      age. The TARGet Kids! practice-based research network is registered at
      www.clinicaltrials.gov as NCT01869530.

PMID- 30101332
TI  - Effect of combined use of a low-carbohydrate, high-protein diet with omega-3
      polyunsaturated fatty acid supplementation on glycemic control in newly diagnosed
      type 2 diabetes: a randomized, double-blind, parallel-controlled trial.
AB  - Background: The combined effect of a low-carbohydrate, high-protein (LCHP) diet
      and omega-3 (n-3) polyunsaturated fatty acid (PUFA) supplementation on patients
      with type 2 diabetes (T2D) is not known. Objective: The aim of this study was to
      evaluate the effect of an LCHP diet combined with omega-3 (LCHP+omega-3) on
      glycemic control in patients with T2D. Design: In this randomized, double-blind,
      parallel-controlled trial, 122 newly diagnosed participants with T2D were
      randomly assigned to receive a high-carbohydrate, low-protein diet with low omega
      3 PUFAs [control (CON)], an LCHP, omega-3, or LCHP+omega-3 diet for 12 wk. The
      ratio of carbohydrate to protein was 42:28 in the LCHP and LCHP+omega-3 diet and
      54:17 in the CON and omega-3 diet. The participants were given 6 g fish oil/d
      (containing 3.65 g docosahexaenoic acid, eicosapentaenoic acid, and
      docosapentaenoic acid/d) in the omega-3 and LCHP+omega-3 diet groups or 6 g corn
      oil/d (placebo) in the CON and LCHP diet groups. Results: Compared with the CON
      diet group, greater decreases in glycated hemoglobin (HbA1c) and fasting glucose
      were observed in all of the other 3 diet groups at 12 wk. Of note, HbA1c
      reduction in the LCHP+omega-3 diet group (-0.51%; 95% CI: -0.64%, -0.37%) was
      greater than that in the LCHP (P = 0.03) and omega-3 (P = 0.01) diet groups at 12
      wk. In terms of fasting glucose, only the LCHP+omega-3 diet group showed a
      significant decrease at 4 wk (P = 0.03 compared with CON). Moreover, the
      reduction in fasting glucose in the LCHP+omega-3 diet group (-1.32 mmol/L; 95%
      CI: -1.72, -0.93 mmol/L) was greater than that in the LCHP (P = 0.04) and omega-3
      (P = 0.03) diet groups at 12 wk. Conclusions: The LCHP+omega-3 diet provided
      greater effects on HbA1c and fasting glucose and faster effects on fasting
      glucose than both the LCHP and omega-3 diets, indicating the potential necessity
      of combining an LCHP diet with omega-3 PUFAs in T2D control. This trial was
      registered at chictr.org.cn/ as ChiCTR-TRC-14004704.

PMID- 30101333
TI  - A randomized controlled-feeding trial based on the Dietary Guidelines for
      Americans on cardiometabolic health indexes.
AB  - Background: The 2010 Dietary Guidelines for Americans (DGA) recommend nutrient
      needs be met by increasing fruit, vegetable, and whole-grain intake with the use
      of low-fat or fat-free dairy products and by reducing sodium, solid fats, and
      added sugars. However, the DGA, as a dietary pattern, have not been tested in an
      intervention trial. Objective: The aim of this study was to evaluate the impact
      of a DGA-based diet compared with a representative typical American diet (TAD) on
      glucose homeostasis and fasting lipids in individuals at risk of cardiometabolic
      disease. Design: A randomized, double-blind, controlled 8-wk intervention was
      conducted in overweight and obese women selected according to indexes of insulin
      resistance or dyslipidemia. Women were randomly assigned to the DGA or TAD group
      (n = 28 DGA and 24 TAD). The TAD diet was based on average adult intake from the
      NHANES 2009-2010. The DGA and TAD diets had respective Healthy Eating Index
      scores of 98 and 62. All foods and beverages were provided during the
      intervention. Oral-glucose tolerance and fasting lipids were evaluated at 0, 2,
      and 8 wk of the intervention. Insulin resistance and sensitivity were estimated
      with the use of surrogates (e.g., homeostasis model assessment of insulin
      resistance). Results: By design, volunteers maintained their weight during the
      intervention. Fasting insulin, glucose, triglycerides, oral-glucose tolerance,
      and indexes of insulin resistance were not affected by either of the diets.
      Systolic blood pressure decreased in the DGA group (~-9 mm Hg; P < 0.05). Total
      and HDL cholesterol also decreased in both groups (P < 0.05). Exploratory
      analysis comparing volunteers entering the study with insulin resistance and
      dyslipidemia with those with only dyslipidemia did not show an effect of pre
      existing conditions on glucose tolerance or fasting lipid outcomes. Conclusions:
      The consumption of a DGA dietary pattern for 8 wk without weight loss reduced
      systolic blood pressure. There were no differences between the DGA and TAD diets
      in fasting insulin, glucose, indexes of insulin resistance, or fasting lipids.
      This trial was registered at www.clinicaltrials.gov as NCT02298725.

PMID- 30101334
TI  - A metagenomic window into the 2-km-deep terrestrial subsurface aquifer revealed
      multiple pathways of organic matter decomposition.
AB  - We have sequenced metagenome of the microbial community of a deep subsurface
      thermal aquifer in the Tomsk Region of the Western Siberia, Russia. Our goal was
      the recovery of near-complete genomes of the community members to enable accurate
      reconstruction of metabolism and ecological roles of the microbial majority,
      including previously unstudied lineages. The water, obtained via a 2.6 km deep
      borehole 1-R, was anoxic, with a slightly alkaline pH, and a temperature around
      45 degrees C. Microbial community, as revealed by 16S rRNA gene profiling over 2
      years, mostly consisted of sulfate-reducing Firmicutes and Deltaproteobacteria,
      and uncultured lineages of the phyla Chlorofexi, Ignavibacteriae and
      Aminicenantes (OP8). 25 composite genomes with more than 90% completeness were
      recovered from metagenome and used for metabolic reconstruction. Members of
      uncultured lineages of Chlorofexi and Ignavibacteriae are likely involved in
      degradation of carbohydrates by fermentation, and are also capable of aerobic and
      anaerobic respiration. The Chlorofexi bacterium has the Wood-Ljungdahl pathway of
      CO2 fixation. The recently identified candidate phylum Riflebacteria accounted
      for 5%-10% of microbial community. Metabolic reconstruction of a member of
      Riflebacteria predicted that it is an anaerobe capable to grow on carbohydrates
      by fermentation or dissimilatory Fe(III) reduction.

PMID- 30101335
TI  - MIPUP: Minimum perfect unmixed phylogenies for multi-sampled tumors via
      branchings and ILP.
AB  - Motivation: Discovering the evolution of a tumor may help identify driver
      mutations and provide a more comprehensive view on the history of the tumor.
      Recent studies have tackled this problem using multiple samples sequenced from a
      tumor, and due to clinical implications, this has attracted great interest.
      However, such samples usually mix several distinct tumor subclones, which
      confounds the discovery of the tumor phylogeny. Results: We study a natural
      problem formulation requiring to decompose the tumor samples into several
      subclones with the objective of forming a minimum perfect phylogeny. We propose
      an Integer Linear Programming formulation for it, and implement it into a method
      called MIPUP. We tested the ability of MIPUP and of four popular tools LICHeE,
      AncesTree, CITUP, Treeomics to reconstruct the tumor phylogeny. On simulated
      data, MIPUP shows up to a 34% improvement under the ancestor-descendant relations
      metric. On four real datasets, MIPUP's reconstructions proved to be generally
      more faithful than those of LICHeE. Availability: MIPUP is available at
      https://github.com/zhero9/MIPUP as open source. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30101336
TI  - LipidFinder on LIPID MAPS: peak filtering, MS searching and statistical analysis
      for lipidomics.
AB  - Summary: We present LipidFinder online, hosted on the LIPID MAPS website, as a
      liquid chromatography/mass spectrometry (LC/MS) workflow comprising peak
      filtering, MS searching and statistical analysis components, highly customized
      for interrogating lipidomic data. The online interface of LipidFinder includes
      several innovations such as comprehensive parameter tuning, a MS search engine
      employing in-house customized, curated and computationally-generated databases,
      and multiple reporting/display options. A set of integrated statistical analysis
      tools which enable users to identify those features which are significantly
      altered under the selected experimental conditions, thereby greatly reducing the
      complexity of the peaklist prior to MS searching is included. LipidFinder is
      presented as a highly flexible, extensible user-friendly online workflow which
      leverages the lipidomics knowledge base and resources of the LIPID MAPS website,
      long recognised as a leading global lipidomics portal. Availability: LipidFinder
      on LIPID MAPS is available at: http://www.lipidmaps.org/data/LF.

PMID- 30101337
TI  - Analysis of medication therapy discontinuation orders in new electronic
      prescriptions and opportunities for implementing CancelRx.
AB  - Objective: To illustrate the need for wider implementation of the CancelRx
      message by quantifying and characterizing the inappropriate usage of new
      electronic prescription (NewRx) messages for communicating discontinuation
      instructions to pharmacies. Materials and Methods: A retrospective analysis on a
      nationally representative random sample of 1 400 000 NewRx messages transmitted
      over 7 days to identify e-prescriptions containing medication discontinuation
      instructions in NewRx text fields. A vocabulary of search terms signifying
      cancellation instructions was formulated and then iteratively refined. True
      positives were subsequently identified programmatically and through manual
      reviews. Two independent reviewers identified incidences in which these
      instructions were associated with high-alert or look-alike-sound-like (LASA)
      medications. Results: We identified 9735 (0.7% of the total) NewRx messages
      containing prescription cancellation instructions with 78.5% observed in the
      Notes field; 35.3% of identified NewRxs were associated with high-alert or LASA
      medications. The most prevalent cancellation instruction types were medication
      strength or dosage changes (39.3%) and alternative therapy replacement orders
      (39.0%). Discussion: While the incidence of prescribers using the NewRx to
      transmit cancellation instructions was low, their transmission in NewRx fields
      not intended to accommodate such information can produce significant potential
      patient safety concerns, such as duplicate or inaccurate therapies. These
      findings reveal the need for wider industry adoption of the CancelRx message by
      electronic health record (EHR) and pharmacy systems, along with clearer guidance
      and improved end-user training, particularly as states increasingly mandate
      electronic prescribing of controlled substances. Conclusion: Encouraging the use
      of CancelRx and reducing the misuse of NewRx fields would reduce workflow
      disruptions and unnecessary risks to patient safety.

PMID- 30101338
TI  - An experiential learning theory of high level wellness: Australian salutogenic
      research.
AB  - At the broadest level, salutogenesis refers to an emphasis on the origins of
      health, as opposed to a predilection with the determinants of disease. Kickbusch
      urges health promotion professionals to adopt a salutogenic orientation;
      directing research and practice towards the question of 'what creates health?'
      This salutogenic study focused on the most pleasant part of the health continuum
      by asking: (i) what is high level wellness and (ii) how do people attain and
      maintain this way of being? Semi-structured interviews were conducted with 25
      Australian adults who reported a 'high' or 'very high' level of wellness, health
      and happiness. Participants described what high level wellness meant to them,
      their wellness journeys, and the things that helped and hindered their wellbeing.
      This information was coded, compared and crafted into a constructivist grounded
      theory. Our interpretation of the data suggests that high level wellness is the
      sense of peace (wellbeing) that comes from knowing, liking and being one's best
      self. Happy, healthy people seem to attain and maintain this way of being over
      time, through a series of self-initiated experiential learning cycles. The
      'experiential learning theory of high level wellness' links and extends
      literature on salutogenesis, eudaimonic wellbeing, self-actualization and
      experiential learning; positioning everyday people as the leaders of their own
      life-long wellness journeys. It also suggests a new dimension for Antonovsky's
      salutogenic theory: aspiring, not just adapting. Future research could explore
      the utility of our approach with a range of populations and professions,
      progressing towards 'high level wellness for all'.

PMID- 30101339
TI  - A powerful conditional gene-based association approach implicated functionally
      important genes for schizophrenia.
AB  - Motivation: It remains challenging to unravel new susceptibility genes of complex
      diseases and the mechanisms in genome-wide association studies. There are at
      least two difficulties, isolation of the genuine susceptibility genes from many
      indirectly associated genes and functional validation of these genes. Results: We
      first proposed a novel conditional gene-based association test which can use only
      summary statistics to isolate independent association genes of a disease.
      Applying this method, we detected 185 genes of independent association with
      schizophrenia. We then designed an in-silico experiment based on expression/co
      expression to systematically validate pathogenic potential of these genes. We
      found that genes of independent association with schizophrenia had more co
      expression pairs in normal postnatal but not prenatal human brain regions than
      expected. Interestingly, no co-expression enrichment was found in the brain
      regions of schizophrenia patients. The genes with independent association also
      had more significant p-values for differential expression between schizophrenia
      patients and controls in the brain regions. In contrast, indirectly associated
      genes or associated genes by other widely-used gene-based tests had no such
      differential expression and co-expression patterns. In summary, this conditional
      gene-based association test is effective for isolating directly associated genes
      from indirectly associated genes, and the results insightfully suggest that
      common variants might contribute to schizophrenia largely by distorting
      expression and co-expression in post-natal brains. Availability: The conditional
      gene-based association test has been implemented in a platform "KGG" in Java and
      is publicly available at http://grass.cgs.hku.hk/limx/kgg/. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30101340
TI  - Methionine deficiency decreases hepatic lipid exportation and induces liver lipid
      accumulation in broilers.
AB  - The objective of the study was to investigate the effects of deficiency or high
      level addition of methionine (Met) in diet on homocysteine (Hcy) metabolism and
      hepatic lipid metabolism in broiler. A completely random design was used with 3
      dietary treatments with the addition of Met from DL-methionine (DLM) at 0%,
      0.22%, and 0.32% in a basal diet. The analyzed dietary Met was 0.271%, 0.485%,
      and 0.584% respectively for the Met-deficient, sufficient, and excessive diet. A
      total of 360 one-day-old male Ross 308 broiler chicks were randomly assigned to
      the treatments. The trial was last for 21 d. Compared to the Met-sufficient diet,
      the Met-deficient diet significantly resulted the decrease of 1 to 21 d growth
      performance and the increase of liver ether extract (EE). Compared to the Met
      sufficient group, the expression of lipid transport gene apolipoprotein B (APOB)
      in both Met-deficient and Met-excessive group was decreased (P < 0.05). However,
      compared to the Met-sufficient group, a decreased of serum low-density
      lipoprotein cholesterol (LDLC) was only shown in birds fed a Met-deficient diet
      (P < 0.05). Although the plasma Hcy content was decreased, the expression of
      Cystathionine beta-synthase (CbetaS) and hepatic inflammatory cytokines included
      interleukin-1 (IL-1) and interleukin-8 (IL-8) was significantly decreased in
      birds fed the Met-deficient diet when compared to those in Met-sufficient group
      (P < 0.05). When compared to the Met-sufficient group, the broilers in high
      dietary Met group had increased levels of catabolic enzyme genes expression
      especially acyl-coenzyme A oxidase 1 (ACOX1) and carbohydrate response element
      binding protein (CHREBP) (P < 0.05), and a decreased content of liver EE. In
      conclusion, dietary Met deficiency decreased the hepatic lipid export and
      subsequently increased the hepatic lipid accumulation. High dietary Met addition
      increased the hepatic lipid catabolism and subsequently decreased the liver lipid
      accumulation.

PMID- 30101341
TI  - Food and nutrition literacy (FNLIT) and its predictors in primary schoolchildren
      in Iran.
AB  - This study used a locally designed and validated questionnaire to describe the
      distribution of food and nutrition literacy (FNLIT) in a cross-sectional sample
      of 803 students aged 10-12 years from elementary schools in Tehran city, Iran.
      Logistic regression was used to assess the extent to which various independent
      covariates were associated with low FNLIT. The data were used to identify
      significant differences using a range of social and cultural variables relevant
      to the context of school students in Iran. The results of the study showed that
      although the total FNLIT level was good, this headline finding masked important
      differences in the sub-domains. More than half of the children (69%) had high
      levels of FNLIT in the cognitive domain, but in the skills domain, very few (3%)
      scored highly. The study also identified some associations between the total
      FNLIT and its subscales and sociodemographic variables including gender, parent's
      education and age, birth order. These results highlighted groups within the
      school population who were at higher risk of having lower FNLIT levels. They also
      indicate that girls feel more able to exert choice and control over food and
      nutrition decisions than boys are but may be less able to do so in practice.
      Overall, these results are a general reminder to schools of the different
      learning needs of children from different family backgrounds. The article
      highlights the need for continuous improvement in the health education curriculum
      of schools in Iran, particularly highlighting the importance of giving greater
      attention to the development of practical food and nutrition skills alongside
      more traditional food and nutrition knowledge. Additional studies (with long-term
      follow-up) are needed to more fully assess and understand the predictors of
      FNLIT.

PMID- 30101342
TI  - PrimedRPA: Primer design for Recombinase polymerase amplification assays.
AB  - Summary: Recombinase polymerase amplification (RPA), an isothermal nucleic acid
      amplification method, is enhancing our ability to detect a diverse array of
      pathogens, thereby assisting the diagnosis of infectious diseases and the
      detection of microorganisms in food and water. However, new bioinformatics tools
      are needed to automate and improve the design of the primers and probes sets to
      be used in RPA, particularly to account for the high genetic diversity of
      circulating pathogens and cross detection of genetically similar organisms.
      PrimedRPA is a python-based package that automates the creation and filtering of
      RPA primers and probe sets. It aligns several sequences to identify conserved
      targets, and filters regions that cross react with possible background organisms.
      Availability and Implementation: PrimedRPA was implemented in Python 3 and
      supported on Linux and MacOS and is freely available from
      http://pathogenseq.lshtm.ac.uk/PrimedRPA.html. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30101344
TI  - A novel method for describing biomechanical properties of the aortic wall based
      on the three-dimensional fluid-structure interaction model.
AB  - OBJECTIVES: Our goal was to present a novel non-invasive approach for assessment
      of aortic wall displacement to describe its biomechanical properties during the
      cardiac cycle. METHODS: The fluid-structure interaction (FSI) technique was used
      to reconstruct aortic wall displacement based on computed tomography angiography
      and 2-dimensional speckle-tracking technique (2DSTT) data collected from 20
      patients [10 with healthy aortas (AA) and 10 with abdominal aortic aneurysms
      (AAAs)]. The mechanical properties of the wall of the aorta were described by the
      Yeoh hyperelastic materials model with alpha and beta parameters, and wall
      displacement was determined with 2DSTT. The mechanical parameters of the wall of
      the aorta in the FSI model were automatically updated in the calculation loop
      until the calculated and clinically measured wall movements were the same.
      RESULTS: Results showed 98% accuracy of FSI compared to 2DSTT for AA and AAA (P >
      0.05). The mean wall deformation for AA was 2.45 +/- 0.12 mm and 2.49 +/- 0.10 mm
      for FSI and 2DSTT, respectively (P = 0.40), whereas that for AAA was 2.84 +/-
      0.44 mm and 2.88 +/- 0.45 mm, respectively (P = 0.83). The FSI analysis indicated
      that the alpha and beta parameters for AA were equal to 14.35 +/- 1.30 N?cm-2 and
      9.33 +/- 1.08 N?cm-2, respectively; and for AAA, alpha was 11.00 +/- 0.49 N?cm-2
      and beta was 79.46 +/- 4.32 N?cm-2. CONCLUSIONS: The FSI technique may be
      successfully applied to assess the mechanical parameters of patient-specific
      aortic walls using computed tomography angiographic and 2DSTT measurements.

PMID- 30101343
TI  - A new PCR assay based on the new gene-SPUL_2693 for rapid detection of Salmonella
      enterica subsp. enterica serovar Gallinarum biovars Gallinarum and Pullorum.
AB  - Salmonella enterica subsp. enterica serovar Gallinarum biovar Gallinarum (S.
      Gallinarum) and biovar Pullorum (S. Pullorum) are gram-negative bacteria, members
      of the most important infectious pathogens, and have caused common problems in
      the poultry industry, especially in the developing countries. O- and H-antigen
      specific anti-sera are commonly for slide and tube agglutination tests to
      identify Salmonella serovars. However, it is both labor intensive and time
      consuming, so there is an urgent need for a new technique for the rapid detection
      of the major Salmonella serovars. In this study, we developed a 1-step PCR assay
      to identify the serovar Gallinarum. This PCR-based assay was based on the
      SPUL_2693 gene, which was located in SPI-19 and found by comparing the genomes of
      the S. Pullorum and S. Gallinarum in the whole data of NCBI. The specificity of
      this gene was evaluated by bioinformatics analysis, and the results showed that
      the SPUL_2693 gene exists in all serovar Gallinarum. The specificity and
      sensitivity of this PCR assay were evaluated in our study. The developed PCR
      assay was able to distinguish the serovar Gallinarum from 27 different Salmonella
      serovars and 5 different non-Salmonella pathogens. The minimum limit of genomic
      DNA of S. Pullorum for PCR detection was 2.143 pg/MUL, and the minimum limit
      number of cells was 6 CFU. This PCR assay was also applied to analyze Salmonella
      strains isolated from a chicken farm in this study. The PCR assay properly
      identified the serovar Gallinarum from other Salmonella serovars, and the results
      were in agreement with the results of a traditional serotyping assay. In general,
      the newly developed PCR-based assay can be used to accurately judge the presence
      of the serovar Gallinarum and can be combined with traditional serotyping assays,
      especially in the case of large quantities of samples.

PMID- 30101345
TI  - Reengagement of HIV-infected children lost to follow-up after active mobile phone
      tracing in a rural area of Mozambique.
AB  - Introduction: Retention in care and reengagement of lost to follow-up (LTFU)
      patients are priority challenges in pediatric HIV care. We aimed to assess
      whether a telephone-call active tracing program facilitated reengagement in care
      (RIC) in the Manhica District Hospital, Mozambique. Methods: Telephone tracing of
      LTFU children was performed from July 2016 to March 2017. Both ART
      (antiretroviral treatment) and preART patients were included in this study. LTFU
      was defined as not attending the clinic for >=120 days after last attended visit.
      Reengagement was determined 3 months after an attempt to contact. Results: A
      total of 144 children initially identified as LTFU entered the active tracing
      program and 37 were reached by means of telephone tracing. RIC was 57% (95% CI,
      39-72%) among children who could be reached versus 18% (95% CI, 11-26%) of those
      who could not be reached (p = 0.001). Conclusion: Telephone tracing could be an
      effective tool for facilitating reengagement in pediatric HIV care. However, the
      difficulty of reaching patients is an obstacle that can undermine the program.

PMID- 30101346
TI  - Dynamics of physiologically relevant noncanonical DNA structures: an overview
      from experimental and theoretical studies.
AB  - DNA is a complex molecule with phenomenal inherent plasticity and the ability to
      form different hydrogen bonding patterns of varying stabilities. These properties
      enable DNA to attain a variety of structural and conformational polymorphic
      forms. Structurally, DNA can exist in single-stranded form or as higher-order
      structures, which include the canonical double helix as well as the noncanonical
      duplex, triplex and quadruplex species. Each of these structural forms in turn
      encompasses an ensemble of dynamically heterogeneous conformers depending on the
      sequence composition and environmental context. In vivo, the widely populated
      canonical B-DNA attains these noncanonical polymorphs during important cellular
      processes. While several investigations have focused on the structure of these
      noncanonical DNA, studying their dynamics has remained nontrivial. Here, we
      outline findings from some recent advanced experimental and molecular simulation
      techniques that have significantly contributed toward understanding the complex
      dynamics of physiologically relevant noncanonical forms of DNA.

PMID- 30101348
TI  - Characterization of the APSES-family transcriptional regulators of Histoplasma
      capsulatum.
AB  - The fungal APSES protein family of transcription factors is characterized by a
      conserved DNA-binding motif facilitating regulation of gene expression in fungal
      development and other biological processes. However, their functions in the
      thermally dimorphic fungal pathogen Histoplasma capsulatum are unexplored.
      Histoplasma capsulatum switches between avirulent hyphae in the environment and
      virulent yeasts in mammalian hosts. We identified five APSES domain-containing
      proteins in H. capsulatum homologous to Swi6, Mbp1, Stu1 and Xbp1 proteins and
      one protein found in related Ascomycetes (APSES-family protein 1; Afp1). Through
      transcriptional analyses and RNA interference-based functional tests we explored
      their roles in fungal biology and virulence. Mbp1 serves an essential role and
      Swi6 contributes to full yeast cell growth. Stu1 is primarily expressed in
      mycelia and is necessary for aerial hyphae development and conidiation. Xbp1 is
      the only factor enriched specifically in yeast cells. The APSES proteins do not
      regulate conversion of conidia into yeast and hyphal morphologies. The APSES
      family transcription factors are not individually required for H. capsulatum
      infection of cultured macrophages or murine infection, nor do any contribute
      significantly to resistance to cellular stresses including cell wall
      perturbation, osmotic stress, oxidative stress or antifungal treatment. Further
      studies of the downstream genes regulated by the individual APSES factors will be
      helpful in revealing their functional roles in H. capsulatum biology.

PMID- 30101350
TI  - The effect of sodium stearoyl-2-lactylate (80%) and tween 20 (20%)
      supplementation in low-energy density diets on growth performance, nutrient
      digestibility, meat quality, relative organ weight, serum lipid profiles, and
      excreta microbiota in broilers.
AB  - A total of 768 1-d-old Ross 308 male broiler chickens with an average body weight
      of 43.64 +/- 0.59 g were used in a 5-wk feeding trial. The chickens were
      distributed into 4 treatments of 12 replications per treatment with 16 chickens
      per pen. Dietary treatments included the following: TRT1, basal diet; TRT2, -40
      kcal diet + 0.05% emulsifier; TRT3, -60 kcal diet + 0.05% emulsifier; TRT4, -80
      kcal diet + 0.05% emulsifier. The emulsifier contained 80% sodium stearoyl-2
      lactylate and 20% tween 20. In our study, the treatment diets had no significant
      effect on growth performance, meat quality, relative organ weight, serum lipid
      profiles, and excreta microbiota. However, the birds were able to grow as well
      with less energy when the emulsifier was added. The supplementation of emulsifier
      in the low-energy diet linearly decreased cholesterol (P = 0.099) and LDL/C (P =
      0.074). The fat digestion of broilers fed with TRT2, TRT3, and TRT4 was
      significantly higher than broilers fed with TRT1 diet. Our study result shows
      that the emulsifier used for the experiment is beneficial in the low-energy diet
      of broiler chickens.

PMID- 30101349
TI  - Kinetics of Soluble Mediators of the Host Response in Ebola Virus Disease.
AB  - Background: The pathophysiology of Ebola virus disease (EVD) is still poorly
      understood. This study aimed at identifying soluble biomarkers that inform on
      disease mechanisms. Methods: Fifty-four soluble mediators of the immune,
      coagulation, and endothelial system were measured in baseline and follow-up
      samples from hospitalized patients with EVD, using Luminex technology. Cross
      sectional expression levels and changes over time were correlated with outcome.
      Results: Levels of circulating proinflammatory cytokines and chemokines, as well
      as markers of endothelial dysfunction and coagulopathy, were elevated on
      admission to hospital in patients who died from EVD as compared to survivors.
      These markers further increased in patients who died and/or decreased over time
      in survivors. In contrast, markers of gut integrity and T-cell response were
      higher in survivors and increased until discharge. Conclusions: Inflammatory
      response, endothelial integrity, gastric tissue protection, and T cell immunity
      play a role in EVD pathophysiology.

PMID- 30101347
TI  - Epilepsyecosystem.org: crowd-sourcing reproducible seizure prediction with long
      term human intracranial EEG.
AB  - Accurate seizure prediction will transform epilepsy management by offering
      warnings to patients or triggering interventions. However, state-of-the-art
      algorithm design relies on accessing adequate long-term data. Crowd-sourcing
      ecosystems leverage quality data to enable cost-effective, rapid development of
      predictive algorithms. A crowd-sourcing ecosystem for seizure prediction is
      presented involving an international competition, a follow-up held-out data
      evaluation, and an online platform, Epilepsyecosystem.org, for yielding further
      improvements in prediction performance. Crowd-sourced algorithms were obtained
      via the 'Melbourne-University AES-MathWorks-NIH Seizure Prediction Challenge'
      conducted at kaggle.com. Long-term continuous intracranial electroencephalography
      (iEEG) data (442 days of recordings and 211 lead seizures per patient) from
      prediction-resistant patients who had the lowest seizure prediction performances
      from the NeuroVista Seizure Advisory System clinical trial were analysed.
      Contestants (646 individuals in 478 teams) from around the world developed
      algorithms to distinguish between 10-min inter-seizure versus pre-seizure data
      clips. Over 10 000 algorithms were submitted. The top algorithms as determined by
      using the contest data were evaluated on a much larger held-out dataset. The data
      and top algorithms are available online for further investigation and
      development. The top performing contest entry scored 0.81 area under the
      classification curve. The performance reduced by only 6.7% on held-out data. Many
      other teams also showed high prediction reproducibility. Pseudo-prospective
      evaluation demonstrated that many algorithms, when used alone or weighted by
      circadian information, performed better than the benchmarks, including an average
      increase in sensitivity of 1.9 times the original clinical trial sensitivity for
      matched time in warning. These results indicate that clinically-relevant seizure
      prediction is possible in a wider range of patients than previously thought
      possible. Moreover, different algorithms performed best for different patients,
      supporting the use of patient-specific algorithms and long-term monitoring. The
      crowd-sourcing ecosystem for seizure prediction will enable further worldwide
      community study of the data to yield greater improvements in prediction
      performance by way of competition, collaboration and
      synergism.10.1093/brain/awy210_video1awy210media15817489051001.

PMID- 30101352
TI  - Advancement in cardiac imaging for treatment of ventricular arrhythmias in
      structural heart disease.
AB  - Over the last decades, substrate-based approaches to ventricular tachycardia (VT)
      ablation have evolved into an important therapeutic option for patients with
      various structural heart diseases (SHD) and unmappable VT. The well-recognized
      limitations of conventional electroanatomical mapping (EAM) to delineate the
      complex 3D architecture of scar, and the potential capability of advanced cardiac
      imaging technologies to provide adjunctive information, have stimulated
      electrophysiologists to evaluate the role of imaging to improve safety and
      efficacy of catheter ablation. In this review, we summarize the histological
      differences between SHD aetiologies related to monomorphic sustained VT and the
      currently available data on the histological validation of cardiac imaging
      modalities and EAM to delineate scar and the arrhythmogenic substrate. We review
      the current evidence of the value provided by cardiac imaging to facilitate VT
      ablation and to ultimately improve outcome.

PMID- 30101351
TI  - Dietary intake of one-carbon metabolism nutrients and DNA methylation in
      peripheral blood.
AB  - Background: Folate and other one-carbon metabolism nutrients are essential to
      enable DNA methylation to occur, but the extent to which their dietary intake
      influences methylation in adulthood is unclear. Objective: We assessed
      associations between dietary intake of these nutrients and DNA methylation in
      peripheral blood, overall and at specific genomic locations. Design: We conducted
      a cross-sectional study using baseline data and samples from 5186 adult
      participants in the Melbourne Collaborative Cohort Study (MCCS). Nutrient intake
      was estimated from a food-frequency questionnaire. DNA methylation was measured
      by using the Illumina Infinium HumanMethylation450 BeadChip array (HM450K). We
      assessed associations of intakes of folate, riboflavin, vitamins B-6 and B-12,
      methionine, choline, and betaine with methylation at individual cytosine-guanine
      dinucleotides (CpGs), and with median (genome-wide) methylation across all CpGs,
      CpGs in gene bodies, and CpGs in gene promoters. We also assessed associations
      with methylation at long interspersed nuclear element 1 (LINE-1), satellite 2
      (Sat2), and Arthrobacter luteus restriction endonuclease (Alu) repetitive
      elements for a subset of participants. We used linear mixed regression, adjusting
      for age, sex, country of birth, smoking, energy intake from food, alcohol intake,
      Mediterranean diet score, and batch effects to assess log-linear associations
      with dietary intake of each nutrient. In secondary analyses, we assessed
      associations with low or high intakes defined by extreme quintiles. Results: No
      evidence of log-linear association was observed at P < 10-7 between the intake of
      one-carbon metabolism nutrients and methylation at individual CpGs. Low intake of
      riboflavin was associated with higher methylation at CpG cg21230392 in the first
      exon of PROM1 (P = 5.0 * 10-8). No consistent evidence of association was
      observed with genome-wide or repetitive element measures of methylation.
      Conclusion: Our findings suggest that dietary intake of one-carbon metabolism
      nutrients in adulthood, as measured by a food-frequency questionnaire, has little
      association with blood DNA methylation. An association with low intake of
      riboflavin requires replication in independent cohorts. This study was registered
      at http://www.clinicaltrials.gov as NCT03227003.

PMID- 30101353
TI  - Ambulatory electrocardiogram monitoring for syncope and collapse: a comparative
      assessment of clinical practice in UK and Germany.
AB  - Aims: Diagnostic ambulatory electrocardiogram (AECG) monitoring is widely used
      for evaluating syncope/collapse. In Europe, two sets of practice guidelines
      [National Institute for Health and Clinical Excellence (NICE) and European
      Society of Cardiology (ESC)] provide recommendations concerning optimal selection
      of AECG devices. However, whether practising physicians' select AECGs based on
      published guidelines is unclear. This study examined AECG use by Emergency
      Department (EDs) physicians and cardiologists in two European countries: Germany
      (D) and United Kingdom (UK). Methods and Results: A quantitative survey was
      undertaken in which 177 respondents participated (ED: UK 33, Germany 40;
      Cardiology: UK 54, Germany 50). The choice of AECG technology varied by
      specialty. Thus, among EDs, despite patients having daily symptoms, 20% (UK), 31%
      (D) of respondents chose an AECG other than Holter monitor. Conversely, when
      monitoring for infrequent events (<monthly), 15-30% (UK and D) indicated choice
      of 24-48 h Holter, 15-30% (UK and D) a conventional event recorder, and only ~50%
      select an insertable cardiac monitor (ICM). Among cardiologists, 6% (UK), 10% (D)
      would not choose a Holter for daily symptoms but, for infrequent symptoms, ~80%
      would select an ICM (UK and D). However, many cardiologists (UK and D) persist
      with Holters for infrequent events despite repeated failure of that technology to
      provide a diagnosis. Conclusions: In evaluation of syncope/collapse, most UK and
      German ED physicians and cardiologists use AECG's according to guidelines, but a
      substantial minority diverge from AECG guideline recommendations.

PMID- 30101354
TI  - Multiple Aneurysms Clipping Through the Eyebrow Approach: 2-Dimensional Operative
      Video.
AB  - The eyebrow approach is a versatile technique that may apply to various vascular
      and tumoral pathologies of the anterior skull base. We present a case of multiple
      aneurysms clipping through the eyebrow approach and we discuss the nuances of
      this technique. A 44-yr-old patient presented with incidentally found aneurysms.
      Angiography showed 2 4.5-mm aneurysms on the left middle cerebral artery (MCA)
      and internal carotid artery (ICA) bifurcations. At surgery, the patient is
      positioned supine with the head elevated, slightly rotated, and extended in order
      to obtain good access and gravity retraction of the brain. A 3-cm incision is
      placed in the eyebrow and a small supraorbital bone flap is raised. The floor of
      the orbit and the edges of the craniotomy are thoroughly drilled in order to
      maximize the working space. After dural opening, the sylvian fissure was widely
      dissected and the MCA aneurysm was identified. A large opening of the sylvian and
      carotid cistern allows retractor free surgery. The ICA bifurcation aneurysm is
      then dissected and clipped. The MCA aneurysm is treated last in order to avoid a
      conflict between instruments especially during clipping. Aneurysms occlusion and
      vessel permeability is verified by Doppler ultrasonography and indocyanine green
      (ICG) angiography. After achieving hemostasis, the dura is closed and a
      subcuticular continuous suture is used at the skin. The postoperative course was
      uneventful. The eyebrow approach allows simultaneous treatment of multiple
      aneurysms of the anterior circle of Willis in selected cases. Proper positioning,
      drilling of the orbital floor and extensive arachnoid dissection are the key
      steps of this procedure.

PMID- 30101355
TI  - A Modified Lateral Orbitotomy Approach to the Superior Orbital Fissure: A Video
      Case Report and Review of Anatomy.
AB  - BACKGROUND: The lateral orbitotomy approach (LOA) is often used for accessing the
      orbital contents and middle skull base; however, most prior descriptions of the
      LOA involve complete drilling of the lateral orbital wall. This practice requires
      retraction of the orbital contents and produces postoperative diplopia that the
      patient experiences for a limited time. OBJECTIVE: To describe a modified LOA
      with partial sparing of the lateral orbital wall for accessing lesions of the
      superior orbital fissure (SOF). METHODS: One patient with a progressively
      enlarging SOF lesion and visual loss underwent a modified LOA for resection. The
      orbital rim lateral to the SOF was removed as a bone flap, and the greater wing
      of the sphenoid inferior to the SOF was drilled to expose the lesion. The lateral
      orbital wall was thinned but was not completely removed. The orbital rim was
      resecured with miniplates and screws. RESULTS: Gross total resection of the SOF
      mass was achieved without unnecessary exposure or retraction of the orbital
      contents. Histopathologic analysis of the resected mass was consistent with a
      cavernous hemangioma. The patient had a good cosmetic outcome without
      complication. CONCLUSION: Modified LOA with partial sparing of the lateral
      orbital wall is a feasible approach for lesions of the SOF.

PMID- 30101356
TI  - Clustering of temporal gene expression data with mixtures of mixed effects models
      with a penalized likelihood.
AB  - Motivation: Clustering algorithms like K-Means and standard Gaussian mixture
      models (GMM) fail to account for the structure of variability of replicated data
      or repeated measures over time. Additionally, a priori cluster number assumptions
      add an additional complexity to the process. Current methods to optimize cluster
      labels and number can be inaccurate or computationally intensive for temporal
      gene expression data with this additional variability. Results: An extension to a
      model-based clustering algorithm is proposed using mixtures of mixed effects
      polynomial regression models and the EM algorithm with an entropy penalized log
      likelihood function (EPEM). The EPEM is used to cluster temporal gene expression
      data with this additional variability. The addition of random effects in our
      model decreased the misclassification error when compared to mixtures of fixed
      effects models or other methods such as K-Means and GMM. Applying our method to
      microarray data from a fracture healing study revealed distinct temporal patterns
      of gene expression. Supplementary information: Supplementary text are available
      at Bioinformatics online.

PMID- 30101357
TI  - Weakening association of parental education: analysis of child health outcomes in
      43 low- and middle-income countries.
AB  - Background: Parental education has been suggested to be an effective instrument
      for improving child health in low- and middle-income countries. Both education
      and child health have improved, however, as well as related factors. These
      changes may have implications for the observed association. Methods: We used
      Demographic and Health Surveys conducted in 43 countries at two points in time,
      between 1991 and 2016, to test if the association of parental education with
      child health has changed over time. We explored how changes relate to commonly
      cited confounders and pathways, including fertility, household living standards,
      health care use, urbanicity and geographical clustering. We used linear
      probability models, Gelbach decomposition, and assessed a range of sensitivity
      specifications. Results: The point estimate for an additional year of maternal
      education has attenuated by 0.27% points (56%) for under-5 mortality, 0.34%
      points (15%) for child stunting, 0.42% points (30%) for child underweight and
      0.09% points (24%) for child wasting. The point estimate for paternal education
      has attenuated by 0.20% points (53%) for under-5 mortality, 0.15% points (8%) for
      child stunting, 0.28% points (24%) for underweight and 0.06% points (19%) for
      wasting. Changes in confounding and mediation by fertility, household living
      standards and urban-rural differences explain to a large extent the attenuations.
      Geospatial clustering increasingly drives the association of parental education
      with child health. Conclusions: The role of parental education in child health
      has attenuated considerably over time in low-resource settings. Decision makers
      should take into account this weakening association when designing policies aimed
      at improving child health.

PMID- 30101358
TI  - Relationship between extralaryngeal endoscopic findings, proton pump inhibitor
      (PPI) response, and pH measures in suspected laryngopharyngeal reflux.
AB  - Laryngopharyngeal reflux (LPR) is a clinical entity diagnosed by history
      laryngoscopic findings that has a variable response to empiric proton-pump
      inhibitor (PPI) therapy. While the reflux finding score (RFS), an endoscopic
      scoring scheme, has been advanced as a measure of LPR, it has not been externally
      validated against symptom severity in practice. Extralaryngeal pharyngeal
      endoscopic findings may have diagnostic utility but remain underexplored. This
      study assesses the correlation between extralaryngeal findings and (1) 24-hour
      oropharyngeal pH & (2) PPI response in patients with suspected LPR. Subjects
      presented to a tertiary care center with laryngeal symptoms >=1 month and reflux
      symptom index (RSI) >=13. Following baseline questionnaires, laryngoscopy, and a
      24-hour oropharyngeal pH probe study, subjects were prescribed 8-12 week
      omeprazole trials. Baseline endoscopic findings were scored in a blinded fashion
      using the RFS and extralaryngeal score criteria, summatively the 'ELS.' PPI
      response was defined as >=50% improvement in RSI. Thirty-three subjects with
      flexible endoscopic recordings completed baseline and follow-up questionnaires.
      The cohort's baseline mean RSI was 23.0 +/- 7.2 with a DeltaRSI = 9.8 after PPI
      therapy. The baseline RFS score averaged 5.3 +/- 2.7. 45% of our subjects was
      found to be PPI responsive. The Cohen's kappa for the ELS but not the RFS was
      significant. There were no significant differences between the RFS (P = 0.10) or
      ELS (P = 0.07) for PPI responders & nonresponders. Oropharyngeal pH measures did
      not correlate with the RFS or ELS. In conclusion, endoscopic scores of laryngeal
      and extralaryngeal findings did not predict PPI response or oropharyngeal acid
      exposure in suspected LPR.

PMID- 30101359
TI  - Down-regulation of 14-3-3 zeta sensitizes human glioblastoma cells to apoptosis
      induction.
AB  - Strong 14-3-3 zeta protein expression plays an important role in tumorigenesis,
      including in the maintenance of cell growth, resistance increase, and the
      prevention of apoptosis. In this study, we focus on two targets: (1) the
      expression of 14-3-3 zeta in the different grades of human astrocytoma (II-IV),
      (2) suppression of 14-3-3 zeta protein expression in glioblastoma derived
      astrocytes by 14-3-3 zeta shRNA lentiviral particles. The tissues of human
      astrocytoma were provided from 30 patients (ten of each grade of astrocytoma).
      Control tissues were obtained from the peritumoral brain zone of those patients
      with glioblastoma. The protein and mRNA expression levels of each astrocytoma
      grade were assessed via western blotting and RT-PCR, respectively. Results
      indicated that 14-3-3 zeta was significantly expressed in glioblastoma multiforme
      (grade IV) and 14-3-3 zeta expression levels enhanced according to the increase
      of astrocytoma malignancy. In the cellular study for knock down of the 14-3-3
      zeta protein, surgical biopsy of glioblastoma was used to isolate primary
      astrocyte. Astrocytes were transduced with 14-3-3 zeta shRNA or non-targeted
      shRNA lentiviral particles. Furthermore, reduction of the 14-3-3 zeta protein
      expression in the astrocytes evaluated through qRT-PCR and western blot after
      transduction of 14-3-3 zeta shRNA lentiviral particles. Moreover, apoptosis
      properties, including DNA fragmentation and ratio increase of Bax/Bcl-2 were
      observed in astrocytes following reduction of 14-3-3 zeta protein expression.
      Further observation indicated that the mitochondrial pathway through release of
      cytochorome c and caspase-3 activity was involved in the apoptosis induction.
      Hence, this study demonstrates a key role of the 14-3-3 zeta protein in
      tumorigenesis but also indicates that 14-3-3 zeta can be considered as a target
      for the astrocytoma treatment specially glioblastoma.

PMID- 30101360
TI  - The clinical relevance of PCL index on the reconstruction of anterior cruciate
      ligament with hamstring tendon autograft.
AB  - The posterior cruciate ligament index (PCL index) has been reported as a
      diagnostic and prognostic marker for anterior cruciate ligament (ACL)
      reconstruction. The clinical relevance of PCL index on the reconstruction of ACL
      with hamstring tendon autograft has not been described in the literature. The
      objective of this study is to evaluate the importance of the PCL index as a
      marker of anatomic reconstruction and of functional improvement of patients
      undergoing ACL reconstruction with HT autograft. Twenty-four patients were
      submitted to ACL reconstruction with HT autograft. The PCL index was assessed by
      magnetic resonance imaging before and after surgery. The functional evaluation
      was performed through the International Knee Documentation Committee (IKDC)
      Subjective Knee Evaluation Form(c) and Knee Society Knee Scoring System(c) (IKS).
      Patients presented a significant positive variation of the PCL index, IKDC and
      IKS scores. There is no significant correlation between PCL index variation and
      IKDC and IKS scores (p > 0.05). Unlike other studies reporting a relationship
      between the PCL index, control of rotational kinematics, and functional
      improvement in patients undergoing ACL reconstruction with bone-patellar tendon
      bone autograft, this study does not demonstrate this association. There is
      evidence in this study to show that the PCL index may be used as an anatomic
      reconstructive marker of ACL but not to predict the clinical outcome in this type
      of reconstruction.

PMID- 30101361
TI  - Unilateral uniplanar modular external fixator for percutaneous proximal femoral
      osteotomy in children: surgical technique.
AB  - Varus derotation femoral osteotomy (VDFO) is a commonly used surgical procedure
      in association with pelvic osteotomy for dislocated hip in developmental hip
      dysplasia. Several types of internal fixation devices were described in the
      literature, but none of them showed a superiority or a lower rate of complication
      over the others. Different types of external fixator were also described for
      proximal osteotomy fixation with good results. We describe the surgical technique
      of the VDFO using a modular external fixator with an illustrative case.

PMID- 30101362
TI  - Clinical and radiological outcome at mean follow-up of 11 years after hip
      arthroscopy.
AB  - INTRODUCTION: The use of hip arthroscopy (HA) has substantially increased over
      the last decade. However, while the benefits of HA after 1 year in patients with
      femoroacetabular impingement (FAI) are well documented, long-term data on the
      progression of osteoarthritis (OA) or patient-reported outcomes (PROMs) are
      lacking. OBJECTIVES: To evaluate long-term clinical and radiological outcomes
      after HA. MATERIALS AND METHODS: Preoperative clinical records, operative notes,
      and radiographs from all patients who underwent HA at our hospital between 1998
      and 2006 were reviewed. Exclusion criteria were previous hip surgery or
      diagnostic HA. Primary endpoints were subsequent total hip arthroplasty (THA) or
      other hip surgery. Secondary endpoints were OA progression and PROMs. RESULTS: HA
      was performed in 92 consecutive patients from 1998 to 2006. Indications for HA
      were FAI, labral lesions, early OA, and focal osteochondral defects. Mean follow
      up was 11.2 years (SD 2.5, range 7.9-16). Data from 43 patients were available
      for analysis; 38 patients were excluded, and 11 were lost to follow-up. 20
      patients had subsequent hip surgery, of which 11 patients required THA. 33
      patients (77%) stated that they would undergo HA again under the same
      circumstances. Longitudinal radiological analysis showed no significant OA
      progression in patients without THA. The Forgotten Joint Score-12 was the only
      PROM to significantly differ between patients who had no further surgery and
      patients who had undergone revision (p = 0.037). CONCLUSION: There was no
      significant OA progression on plain radiography at an average of 11 years post
      HA. Sound indication criteria is essential, as 45% of patients required
      subsequent surgery.

PMID- 30101363
TI  - Application of decellularized allograft for primary repair of congenital heart
      disease in Japan.
AB  - A 6-month-old infant with a double outlet right ventricle, doubly committed
      ventricular septal defect, and right ventricle outflow tract (RVOT) stenosis
      underwent intracardiac repair with RVOT reconstruction using a fresh
      decellularized allograft derived from a 1-year-old heart transplant recipient in
      Japan. Early postoperative evaluation via echocardiography and cardiac magnetic
      resonance imaging revealed that the pulmonary allograft and cardiac function were
      stable. This is the first case report on using a decellularized heart valve,
      which was resected from a heart transplant recipient, for primary repair of
      congenital heart disease in Japan.

PMID- 30101364
TI  - When zebras run with horses - inherited metabolic diseases come mainstream.

PMID- 30101365
TI  - Management and outcome of multifetal gestation in a 35-year-old woman with
      childhood-onset membranoproliferative glomerulonephritis type I.
AB  - A 35-year-old woman with membranoproliferative glomerulonephritis type I had
      quintuplet gestation after induced ovulation. Her serum creatinine level and
      estimated glomerular filtration rate were 0.86 mg/dL and 61.5 mL/min/1.73 m2
      before pregnancy. Blood pressure was normal and urinary protein to creatinine
      ratio was 0.2 g/gCr. Prednisolone 10 mg on alternate-day administration was
      continued during pregnancy. At 10 weeks of gestation transvaginal selective
      embryo reduction was performed and five embryos were reduced to twins.
      Hypertension occurred at 20 weeks of gestation. She developed nephrotic syndrome
      and serum creatinine level increased to 1.29 mg/dL. Elective cesarean section was
      performed at 28 weeks of gestation and dichorionic diamniotic twins were born.
      After delivery blood pressure, serum creatinine level, estimated glomerular
      filtration rate and serum albumin level in their mother returned to baseline. Her
      twin infants were well at discharge from neonatal-intensive-care-unit. Incidence
      of multifetal pregnancies due to the improvement of assisted reproduction
      technologies and ovulation-inducing hormones has been increasing. Management for
      multifetal pregnancy in women with chronic kidney disease will be needed further.

PMID- 30101367
TI  - Chloro-Modified Magnetic Fe3O4@MCM-41 Core-Shell Nanoparticles for L-Asparaginase
      Immobilization with Improved Catalytic Activity, Reusability, and Storage
      Stability.
AB  - This paper describes a new support that permits to efficient immobilization of L
      asparaginase (L-ASNase). For this purpose, Fe3O4 magnetic nanoparticles were
      synthesized and coated by MCM-41. 3-chloropropyltrimethoxysilane (CPTMS) was used
      as a surface modifying agent for covalent immobilization of L-ASNase on the
      magnetic nanoparticles. The chemical structure; thermal, morphological, and
      magnetic properties; chemical composition; and zeta potential value of Fe3O4@MCM
      41-Cl were characterized by Fourier transform infrared spectroscopy (FTIR),
      thermogravimetric analysis (TGA), differential thermal analysis (DTA),
      differential scanning calorimetry (DSC), vibrating sample magnetometer (VSM),
      scanning electron microscope (SEM), energy dispersive X-ray (EDX), X-ray
      diffraction patterns (XRD), and zeta-potential measurement. The immobilization
      efficiency onto Fe3O4@MCM-41-Cl was detected as 63%. The reusability, storage,
      pH, and thermal stabilities of the immobilized L-ASNase were investigated and
      compared to that of soluble one. The immobilized enzyme maintained 42.2% of its
      original activity after 18 cycles of reuse. Furthermore, it was more stable
      towards pH and temperature compared with soluble enzyme. The Michaelis-Menten
      kinetic properties of immobilized L-ASNase showed a lower Vmax and a similar Km
      compared to soluble L-ASNase. Immobilized enzyme had around 47 and 32.5% residual
      activity upon storage a period of 28 days at 4 and 25  degrees C, respectively.
      In conclusion, the Fe3O4@MCM-41-Cl@L-ASNase core-shell nanoparticles could
      successfully be used in industrial and medical applications.

PMID- 30101368
TI  - Is Henoch-Schonlein purpura a susceptibility factor for functional
      gastrointestinal disorders in children?
AB  - Henoch-Schonlein purpura (HSP), the most common childhood vasculitis is
      characterized by non-thrombocytopenic palpable purpura, arthritis/arthralgia,
      abdominal pain and renal involvement. Functional gastrointestinal disorders
      (FGIDs) are heterogeneous disease spectrum with unclear etiology and include the
      most common subtypes: functional dyspepsia, irritable bowel syndrome (IBS),
      functional abdominal pain and functional constipation. Formerly, FGIDs were known
      as non-organic disorders; however, recent advances revealed that low-grade
      inflammation may also play a role. We aimed to clarify whether HSP predisposes to
      FGIDs in pediatric population. Seventy-four children with HSP, diagnosed at least
      6 months before the study and 78 healthy controls were enrolled to the study.
      Patients with red flag signs for organic GI disorders were excluded. Rome IV
      criteria were utilized for FGIDs diagnosis. We compared the frequencies of FGIDs
      between HSP patients and healthy subjects. We also examined the parameters
      including age, abdominal pain, arthralgia, bloody stool, renal involvement and
      treatment with corticosteroids and laboratory results at HSP diagnosis such as
      erythrocyte sedimentation rate, C-reactive protein, hemoglobin, leukocytes and
      platelet counts among patients with and without FGIDs. Overall FGIDs and IBS
      frequency were 35.1% (n = 26) and 10.8% (n = 8) in HSP patients, 19.2% (n = 15)
      and 2.6% (n = 2) in healthy controls, respectively. Disease characteristics and
      laboratory parameters at disease onset were similar between HSP patients with and
      without FGIDs. Overall FGIDs rate, particularly IBS were statistically higher in
      HSP patients. We speculate that children with preceding HSP may be predisposed to
      FGIDs. Since the FGIDs pathogenesis is still remains unclear, further studies are
      needed to confirm this hypothesis and clarify the etiology. Physicians also
      should pay attention to FGIDs in HSP patients with ongoing abdominal pain and
      thus prevent this comorbidity with dietary and psychologic measures.

PMID- 30101366
TI  - D-ribose induces nephropathy through RAGE-dependent NF-kappaB inflammation.
AB  - Recently, aberrantly high levels of D-ribose have been discovered in type II
      diabetic patients. D-ribose glycates proteins more rapidly than D-glucose,
      resulting in the production of advanced glycation end products (AGEs).
      Accumulations of these products can be found in impaired renal function, but the
      mechanisms are poorly understood. The present study tested whether D-ribose
      induces renal dysfunction via the RAGE-dependent NF-kappaB signaling pathway. In
      vivo, administration of D-ribose was found to lower blood glucose and regulate
      insulin tolerance. Compared to controls, urine nitrogen and creatinine excretion
      were increased in mice receiving D-ribose and were accompanied by severe
      pathological renal damage. Furthermore, immunohistochemistry showed that NF
      kappaB, AGEs, and receptor of AGEs (RAGE) increased in the kidneys of the mice
      with D-ribose treatment. In vitro, by western blot and immunofluorescent
      staining, we confirmed that D-ribose induced NF-kappaB activation and
      accumulation of AGEs and RAGE in mesangial cells. By co-immunoprecipitation, we
      found that the pull-down of RAGE remarkably increased the expression of NF
      kappaB. Silencing the RAGE gene blocked the phosphorylation of NF-kappaB induced
      by D-ribose. These results strongly suggest that D-ribose induced NF-kappaB
      inflammation in a RAGE-dependent manner, which may be a triggering mechanism
      leading to nephropathy.

PMID- 30101369
TI  - Evaluation of disease activity in a low-income juvenile idiopathic arthritis
      cohort.
AB  - Determine disease activity in a low income juvenile idiopathic arthritis (JIA)
      cohort. 164 JIA patients from families with less than US$ 4500.00/capita mean
      annual income followed in Fortaleza-CE, Brazil, were cross-sectionally evaluated
      between May 2015-April 2016. Mean age was 14 +/- 5.1 years (95 female) with 10.31
      +/- 3.7 years disease duration. Polyarticular category predominated, with 63
      (38.4%) patients, followed by 40 (24%) enthesitis-related (ERA), and 36 (22%)
      oligoarticular. All but 1 out of 84 parents declared less than US$ 10,000.00
      annual family income. Eighty-eight (60.7%) were receiving methotrexate and 19
      (13%) leflunomide including 12 (63%) using both; 46 (28%) were on biologic DMARD
      including 20 (43.5%) adalimumab, 17 (41.5) etanercept, 5 (10.8%) tocilizumab, 2
      (4.2%) abatacept, and 1 (2.1%) each on infliximab and canakinumab. Mean CHAQ and
      JADAS27 were 0.36 +/- 0.55 and 5.31 +/- 8.5, respectively. Thirty-two (20%) out
      of 159 patients had deformities. A bivariate analysis revealed that polyarticular
      had more deformities than oligoarticular patients (p = 0.002; OR = 2.389; 95% CI
      1.37-4.14). Logistic regression showed no association between high JADAS and
      family income (p = 0.339; OR = 1.45; 95% CI 0.67-3.31). A general linear model
      showed significantly lower CHAQ score in patients from families earning more as
      compared to those earning less than 300.00 US$ monthly (p = 0.002). This study
      reports JIA disease activity in a low income population. Low income apparently
      did not influence prognosis given the low mean JADAS27 and CHAQ scores vis-a-vis
      data from other cohorts.

PMID- 30101372
TI  - Messengers for morphogenesis: inositol polyphosphate signaling and yeast
      pseudohyphal growth.
AB  - In response to various environmental stimuli and stressors, the budding yeast
      Saccharomyces cerevisiae can initiate a striking morphological transition from
      its classic growth mode as isolated single cells to a filamentous form in which
      elongated cells remain connected post-cytokinesis in multi-cellular pseudohyphae.
      The formation of pseudohyphal filaments is regulated through an expansive
      signaling network, encompassing well studied and highly conserved pathways
      enabling changes in cell polarity, budding, cytoskeletal organization, and cell
      adhesion; however, changes in metabolite levels underlying the pseudohyphal
      growth transition are less well understood. We have recently identified a
      function for second messenger inositol polyphosphates (InsPs) in regulating
      pseudohyphal growth. InsPs are formed through the cleavage of membrane-bound
      phosphatidylinositol 4,5-bisphosphate (PIP2), and these soluble compounds are now
      being appreciated as important regulators of diverse processes, from phosphate
      homeostasis to cell migration. We find that kinases in the InsP pathway are
      required for wild-type pseudohyphal growth, and that InsP species exhibit
      characteristic profiles under conditions promoting filamentation. Ratios of the
      doubly phosphorylated InsP7 isoforms 5PP-InsP5 to 1PP-InsP5 are elevated in
      mutants exhibiting exaggerated pseudohyphal growth. Interestingly, S. cerevisiae
      mutants deleted of the mitogen-activated protein kinases (MAPKs) Kss1p or Fus3p
      or the AMP-activated kinase (AMPK) family member Snf1p display mutant InsP
      profiles, suggesting that these signaling pathways may contribute to the
      regulatory mechanism controlling InsP levels. Consequently, analyses of yeast
      pseudohyphal growth may be informative in identifying mechanisms regulating
      InsPs, while indicating a new function for these conserved second messengers in
      modulating cell stress responses and morphogenesis.

PMID- 30101370
TI  - Routing of thylakoid lumen proteins by the chloroplast twin arginine transport
      pathway.
AB  - Thylakoids are complex sub-organellar membrane systems whose role in
      photosynthesis makes them critical to life. Thylakoids require the coordinated
      expression of both nuclear- and plastid-encoded proteins to allow rapid response
      to changing environmental conditions. Transport of cytoplasmically synthesized
      proteins to thylakoids or the thylakoid lumen is complex; the process involves
      transport across up to three membrane systems with routing through three aqueous
      compartments. Protein transport in thylakoids is accomplished by conserved
      ancestral prokaryotic plasma membrane translocases containing novel adaptations
      for the sub-organellar location. This review focuses on the evolutionarily
      conserved chloroplast twin arginine transport (cpTat) pathway. An overview is
      provided of known aspects of the cpTat components, energy requirements, and
      mechanisms with a focus on recent discoveries. Some of the most exciting new
      studies have been in determining the structural architecture of the membrane
      complex involved in forming the point of passage for the precursor and binding
      features of the translocase components. The cpTat system is of particular
      interest because it transports folded protein domains using only the proton
      motive force for energy. The implications for mechanism of translocation by
      recent studies focusing on interactions between membrane Tat components and with
      the translocating precursor will be discussed.

PMID- 30101371
TI  - Mechanoregulation and pathology of YAP/TAZ via Hippo and non-Hippo mechanisms.
AB  - Yes-associated protein (YAP) and its paralog WW domain containing transcription
      regulator 1 (TAZ) are important regulators of multiple cellular functions such as
      proliferation, differentiation, and survival. On the tissue level, YAP/TAZ are
      essential for embryonic development, organ size control and regeneration, while
      their deregulation leads to carcinogenesis or other diseases. As an underlying
      principle for YAP/TAZ-mediated regulation of biological functions, a growing body
      of research reveals that YAP/TAZ play a central role in delivering information of
      mechanical environments surrounding cells to the nucleus transcriptional
      machinery. In this review, we discuss mechanical cue-dependent regulatory
      mechanisms for YAP/TAZ functions, as well as their clinical significance in
      cancer progression and treatment.

PMID- 30101373
TI  - Fucosylation genes as circulating biomarkers for lung cancer.
AB  - PURPOSE: Fucosyltransferases (FUTs) catalyze fucosylation, which plays a central
      role in biological processes. Aberrant fucosylation is associated with malignant
      transformation. Here we investigated whether transcriptional levels of genes
      coding the FUTs in plasma could provide cell-free circulating biomarkers for lung
      cancer. METHODS: mRNA expression of all 13 Futs (Fut1-11, Pofut1, and Pofut2) was
      evaluated by PCR assay in 48 lung tumor tissues and the 48 matched noncancerous
      lung tissues, and plasma of 64 lung cancer patients and 32 cancer-free
      individuals to develop plasma Fut biomarkers. The developed plasma Fut biomarkers
      were validated in an independent cohort of 40 lung cancer patients and 20
      controls for their diagnostic performance. RESULTS: Four of the 13 Futs showed a
      different transcriptional level in 48 lung tumor tissues compared with the 48
      matched nonconscious tissues (all < 0.05). Two (Fut8, and Pofut1) of the four
      Futs had a higher plasma level in 64 lung cancer patients compared with 32
      control subjects, and consistent with that in lung tissue specimens. Combined
      analysis of the two Futs produced 81% sensitivity and 86% specificity for
      diagnosis of lung cancer, and was independent of stage and histology of lung
      tumors. The diagnostic performance of the two plasma biomarkers was successfully
      validated in the different cohort of 40 lung cancer patients and 20 control
      individuals. CONCLUSION: The fucosylation genes may provide new circulating
      biomarkers for the early detection of lung cancer.

PMID- 30101374
TI  - Clinical utility of assessing PTEN and ERG protein expression in prostate cancer
      patients: a proposed method for risk stratification.
AB  - OBJECTIVES: To assess the prognostic value of ERG and PTEN protein expression as
      two of the most common genetic aberration in men with prostate cancer managed non
      surgically by androgen deprivation therapy (ADT). MATERIALS AND METHODS: 463
      tumor samples were assessed by double immunohistochemistry stains for ERG and
      PTEN and data correlated with clinical pathological features including, Gleason
      score, patients' outcome and ADT. RESULTS: ERG expression and PTEN protein loss
      were present in 28.2% and 38% of total patients respectively. There was a
      significant interplay between ERG and PTEN expression with 21.8% PTEN negative
      tumors being ERG positive (p < 0.001). Both ERG and PTEN showed significant
      association with lethal disease in all patients and those treated with prior ADT
      representing castrate-resistant disease. However, only PTEN remained significant
      in multivariable proportional hazards regression analysis, when including Gleason
      score and patients' age. Depending on patient's subgroup, intact positive PTEN
      intensity showed better cancer-specific survival with HR ranging from 0.25 to 0.4
      compared to tumors with loss of PTEN expression. Assessing combined marker
      status, patients with decreased PTEN intensity without ERG positivity showed the
      worst clinical outcome compared to those with no PTEN loss and no ERG expression,
      where they had best clinical outcome. Patients with ERG expression with or
      without PTEN loss showed intermediate risk in relation to lethal disease.
      CONCLUSION: This study confirms a significant prognostic role for assessing ERG
      and PTEN in men with prostate cancer. It supports a role for utilizing combined
      ERG/PTEN status clinically and prospectively for stratifying PCa patients into
      different prognostic groups.

PMID- 30101375
TI  - Pharmacovigilance in a rare disease: example of the VIGIAPATH program in
      pulmonary arterial hypertension.
AB  - Spontaneous reporting is the primary method used in pharmacovigilance (PV) to
      detect drug safety signal. Specific criteria used in pharmacovigilance to prove
      accountability of a drug are rarely present in rare disease. The low number of
      alerts also makes it challenging. The aim of this commentary is to raise
      awareness among pharmacists on issues and opportunities for pharmacovigilance in
      rare diseases, taking pulmonary arterial hypertension (PAH) as example, from
      which a subset of cases are drug-induced. It is demonstrated how a dedicated
      program named VIGIAPATH created to reinforce pharmacovigilance of drug-induced
      pulmonary arterial hypertension at a national level, led to increase self
      reporting and confirm safety signals. Thanks to a specific program such as
      VIGIAPATH, pharmacists can play an important role in communication with
      clinicians, patients and regulatory agencies, facilitating the detection of
      potential safety signals at an early stage in rare disease.

PMID- 30101376
TI  - Prophylactic selective arterial embolization for renal angiomyolipomas: efficacy
      and evaluation of predictive factors of significant shrinkage.
AB  - PURPOSE: To evaluate the efficacy of prophylactic selective arterial embolization
      (SAE) of angiomyolipomas (AMLs) and to find out predictive factors of significant
      shrinkage of AMLs after SAE. METHODS: Patients receiving prophylactic SAE for
      renal AMLs with complete medical records were included. The changes of the size,
      urine erythrocyte counts, and serum creatinine of all patients pre- and post
      embolization were assessed. Demographic data, symptoms, the background of
      tuberous sclerosis complex (TSC), aneurysms, enhancement features, initial tumor
      sizes, and serum creatinine pre-embolization were estimated as predictive factors
      of significant shrinkage in size. RESULTS: Forty-five patients receiving
      prophylactic SAE for AMLs successfully in our center were included with median
      follow-up of 14.0 months (interquartile range 6.5-40.5). Mean size of AMLs
      decreased from 10.7 +/- 6.2 to 8.3 +/- 5.9 cm by 23.4% +/- 20.6% at the latest
      follow-up (P < 0.001). Urine erythrocytes decreased significantly after SAE (11.1
      [interquartile range 5.7-23.2] vs. 6.4 [interquartile range 2.7-13.4], P <
      0.001). In addition, there was no significant change between the serum creatinine
      before and after embolization (81.8 +/- 14.9 mmol/L vs. 83.6 +/- 17.1 mmol/L, P =
      0.224). Of the variables mentioned above, only the enhanced area of AMLs before
      SAE was statistically significant between the groups with and without significant
      shrinkage (P < 0.001). In multiv-ariate analysis, enhanced area < 25% (AOR =
      0.015, 95% CI 0.001-0.367) and having the background of TSC (AOR = 0.056, 95% CI
      0.004-0.799) were identified as predictive factors of significant shrinkage of
      the tumors. CONCLUSIONS: Prophylactic SAE is effective in reducing the size of
      renal AMLs and decreasing urine erythrocytes with preservation of renal function.
      Significant shrinkage of AMLs after SAE is modulated by the enhanced area and the
      background of TSC.

PMID- 30101377
TI  - Hyperinsulinemia precedes insulin resistance in offspring rats exposed to
      angiotensin II type 1 autoantibody in utero.
AB  - OBJECTIVE: Insulin resistance is highly associated with an adverse intrauterine
      environment. We previously reported that fetal rats exposed to angiotensin II
      type 1 receptor (AT1R) autoantibody (AT1-AA) displayed increased susceptibility
      to metabolic diseases during middle age. However, the timing of the onset of
      insulin resistance remains unknown. In this study, we examined the offspring of
      AT1-AA-positive rats, tracking the development of insulin resistance. METHODS:
      Pregnant rats were intravenously injected with AT1-AA. Afterwards, we collected
      serum samples and liver tissues of the offspring at various stages, including
      gestation day 18, 3 weeks (weaning period), 18 weeks (young adulthood), and 48
      weeks (middle age) after birth. RESULTS: Compared with saline control group,
      hepatic vacuolar degeneration was visible in AT1-AA offspring rats as early as 3
      weeks; hyperinsulinemia and impaired glucose tolerance occurred at 18 weeks of
      age, however, insulin resistance was not observed until 48 weeks. At 18 weeks we
      detected suppressed protein levels of insulin receptor (IR) but increased levels
      of IR substrate 1 (IRS1) in the liver of AT1-AA group rats. Interestingly, both
      IR and IRS1/2 were significantly decreased at 48 weeks. Liver proteomic analysis
      indicated that the differences in protein expression between the AT1-AA and
      control rats became more pronounced with age, particularly in terms of
      mitochondrial energy metabolism. CONCLUSION: Rats exposed to AT1-AA in utero
      developed hyperinsulinemia from young adulthood which subsequently progressed to
      insulin resistance, and was linked with abnormal hepatic structure and impaired
      IR signaling. Additionally, dysregulation of energy metabolism may play a
      fundamental role in predisposing offspring to insulin resistance.

PMID- 30101380
TI  - Public Recognition and Perceptions of Obsessive Compulsive Disorder.
AB  - Previous research has indicated that the public's knowledge on obsessive
      compulsive disorder (OCD) is poor. Public understanding and perception of OCD may
      be one contributor to this issue. Given that mental health literacy is an
      important first step for those to receive the appropriate care, we sought to
      understand more about the public's awareness and perceptions of OCD. Data
      regarding knowledge of OCD were collected through a New York statewide telephone
      survey (N = 806). Results indicated that those who had never heard of OCD were
      more likely to be ethnic minorities, have a lower income, and less education.
      Most participants described OCD either in terms of compulsions or in terms of
      perfectionism. Almost half (46.5%) of participants did not think there is a
      difference between someone with OCD and someone who is obsessive-compulsive.
      These findings are consistent with previous literature regarding race and
      treatment seeking behaviors.

PMID- 30101379
TI  - 1-800-Externship: The Use of Hotlines as a Training Modality for Future
      Clinicians.
AB  - Mental health on college campuses is a growing issue. Despite a rise in demand
      for services, counseling centers generally offer assistance during business
      hours, with a limited number of clinicians. Hotlines can provide an avenue for
      suicide prevention and intervention while offering training to graduate
      counseling students. The present study used a qualitative approach to examine the
      benefits and challenges of using hotlines as a clinical training modality.
      Interviews with nine graduate students volunteering at a hotline were analyzed
      using a consensual qualitative research methodology. Several domains were
      identified, including: three domains related to initial involvement with a
      clinical training experience at a hotline, four related to the experience of
      volunteering, and five related to the connection of the clinical training
      experience to the participant's development as a clinician. Hotlines as a
      training modality can be used to benefit the community and contribute to the
      development of future clinicians.

PMID- 30101381
TI  - Detecting senescent fate in mesenchymal stem cells: a combined cytofluorimetric
      and ultrastructural approach.
AB  - Senescence can impair the therapeutic potential of stem cells. In this study,
      senescence-associated morphofunctional changes in periosteum-derived progenitor
      cells (PDPCs) from old and young individuals were investigated by combining
      cytofluorimetry, immunohistochemistry, and transmission electron microscopy. Cell
      cycle analysis demonstrated a large number of G0/G1 phase cells in PDPCs from old
      subjects and a progressive accumulation of G0/G1 cells during passaging in
      cultures from young subjects. Cytofluorimetry documented significant changes in
      light scattering parameters and closely correlated with the ultrastructural
      features, especially changes in mitochondrial shape and autophagy, which are
      consistent with the mitochondrial-lysosomal axis theory of ageing. The combined
      morphological, biofunctional, and ultrastructural approach enhanced the flow
      cytometric study of PDPC ageing. We speculate that impaired autophagy, documented
      in replicative senescent and old PDPCs, reflect a switch from quiescence to
      senescence. Its demonstration in a tissue with limited turnover-like the cambium
      layer of the periosteum, where reversible quiescence is the normal stem cell
      state throughout life-adds a new piece to the regenerative medicine jigsaw in an
      ageing society.

PMID- 30101378
TI  - The safety and efficacy of once-weekly glucagon-like peptide-1 receptor agonist
      semaglutide in patients with type 2 diabetes mellitus: a systemic review and meta
      analysis.
AB  - OBJECTIVES: To investigate the safety and efficacy of once-weekly glucagon-like
      peptide-1 (GLP-1) receptor agonist semaglutide as monotherapy or add-on to other
      antihyperglycaemic agents (AHAs) in patients with type 2 diabetes mellitus
      (T2DM). METHODS: PubMed, Embase, Cochrane library and ClinicalTrials.gov were
      searched from the inception to January 18, 2018. Randomised controlled trials
      (RCTs) comparing semaglutide with placebo or other AHAs in T2DM patients were
      included in our meta-analysis. Risk ratio (RR) and mean difference (MD) with 95%
      confidence intervals (CI) were used to evaluate the outcomes. RESULTS: A total of
      11 studies with 9519 patients were included in our meta-analysis. The results
      revealed that compared with placebo or other AHAs, semaglutide had further
      reduced the level of haemoglobin A1c (HbA1c) [MD 1.03%, 95% CI (0.85%, 1.22%), p
      < 0.00001], self-measured plasma glucose (SMPG) [MD 1.19 mmol/L, 95% CI (0.84
      mmol/L, 1.53 mmol/L), p < 0.00001], fasting plasma glucose (FPG) [MD 1.33 mmol/L,
      95% CI (0.97 mmol/L, 1.69 mmol/L), p < 0.00001] and weight [MD 3.61 kg, 95% CI
      (3.05 kg, 4.17 kg), p < 0.00001] and significantly increased participants who
      achieved HbA1c < 7.0% [RR 2.26, 95% CI (1.89, 2.70), p < 0.00001] in T2DM
      patients. Semaglutide had a significant increase in the incidence of adverse
      events (AEs) [RR 1.06, 95% CI (1.02, 1.11), p < 0.0001] and an analogous
      incidence in serious adverse events (SAEs) [RR 0.94, 95% CI (0.86, 1.02), p =
      0.11] and hypoglycaemic events (severe or blood glucose (BG)-confirmed
      symptomatic) [RR 0.93, 95% CI (0.74, 1.16), p = 0.50] compared with the control
      group. CONCLUSIONS: This article revealed that semaglutide had a favourable
      efficacy and safety in treating T2DM patients. It maybe a superior choice for
      T2DM patients who have obesity or a poor adherence to daily AHAs.

PMID- 30101383
TI  - The control of a virtual automatic car based on multiple patterns of motor
      imagery BCI.
AB  - Multiple degrees of freedom (DOF) commands are required for a brain-actuated
      virtual automatic car, which makes the brain-computer interface (BCI) control
      strategy a big challenge. In order to solve the challenging issue, a mixed model
      of BCI combining P300 potentials and motor imagery had been realized in our
      previous study. However, compared with single model BCI, more training procedures
      are needed for the mixed model and more mental workload for users to bear. In the
      present study, we propose a multiple patterns of motor imagery (MPMI) BCI method,
      which is based on the traditional two patterns of motor imagery. Our motor
      imagery BCI approach had been extended to multiple patterns: right-hand motor
      imagery, left-hand motor imagery, foot motor imagery, and both hands motor
      imagery resulting in turning right, turning left, acceleration, and deceleration
      for a virtual automatic car control. Ten healthy subjects participated in online
      experiments, the experimental results not only show the efficiency of our
      proposed MPMI-BCI strategy but also indicate that those users can control the
      virtual automatic car spontaneously and efficiently without any other visual
      attention. Furthermore, the metric of path length optimality ratio (1.23) is very
      encouraging and the time optimality ratio (1.28) is especially remarkable.
      Graphical Abstract The paradigm of multiple patterns of motor imagery detection
      and the relevant topographies of CSP weights for different MI patterns.

PMID- 30101382
TI  - Transcriptome analysis in Malus halliana roots in response to iron deficiency
      reveals insight into sugar regulation.
AB  - Iron (Fe) deficiency is a frequent nutritional problem limiting apple production
      in calcareous soils. The utilization of rootstock that is resistant to Fe
      deficiency is an effective way to solve this problem. Malus halliana is an Fe
      deficiency-tolerant rootstock; however, few molecular studies have been conducted
      on M. halliana. In the present work, a transcriptome analysis was combined with
      qRT-PCR and sugar measurements to investigate Fe deficiency responses in M.
      halliana roots at 0 h (T1), 12 h (T2) and 72 h (T3) after Fe deficiency stress.
      Total of 2473, 661, and 776 differentially expressed genes (DEGs) were identified
      in the pairs of T2 vs. T1, T3 vs. T1, and T3 vs. T2, respectively. Several DEGs
      were enriched in the photosynthesis, glycolysis and gluconeogenesis, tyrosine
      metabolism and fatty acid degradation pathways. The glycolysis and photosynthesis
      pathways were upregulated under Fe deficiency. In this experiment, sucrose
      accumulated in Fe-deficient roots and leaves. However, the glucose content
      significantly decreased in the roots, while the fructose content significantly
      decreased in the leaves. Additionally, 15 genes related to glycolysis and sugar
      synthesis and sugar transport were selected to validate the accuracy of the
      transcriptome data by qRT-PCR. Overall, these results indicated that sugar
      synthesis and metabolism in the roots were affected by Fe deficiency. Sugar
      regulation is a way by which M. halliana responds to Fe deficiency stress.

PMID- 30101384
TI  - Benzoxazole derivatives: design, synthesis and biological evaluation.
AB  - BACKGROUND: A new series of benzoxazole analogues was synthesized and checked for
      their in vitro antibacterial, antifungal and anticancer activities. RESULTS AND
      DISCUSSION: The synthesized benzoxazole compounds were confirmed by IR, 1H/13C
      NMR, mass and screened for their in vitro antimicrobial activity against Gram
      positive bacterium: Bacillus subtilis, four Gram-negative bacteria: Escherichia
      coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi and two
      fungal strains: Candida albicans and Aspergillus niger using tube dilution
      technique and minimum inhibitory concentration (MIC) was noted in uM and compared
      to ofloxacin and fluconazole. Human colorectal carcinoma (HCT116) cancer cell
      line was used for the determination of in vitro anticancer activity (IC50 value)
      by Sulforhodamine B assay using 5-fluorouracil as standard drug. CONCLUSION: The
      performed study indicated that the compounds 1, 10, 13, 16, 19, 20 and 24 had
      highest antimicrobial activity with MIC values comparable to ofloxacin and
      fluconazole and compounds 4, 6, 25 and 26 had best anticancer activity in
      comparison to 5-fluorouracil.

PMID- 30101385
TI  - Patient and Community Health Worker Perceptions of Community Health Worker
      Clinical Integration.
AB  - Traditional community health workers (CHWs) are expanding their role into
      clinical settings (cCHW) to support patients with care coordination and advocacy
      services. We investigated the potential to integrate cCHWs, via evaluation of
      patients' and CHWs' key demographics, needs, and abilities. This mixed-methods
      study, including adult patients and CHWs, was conducted in the Inland Valley of
      Southern California, between 2016 and 2017. Survey data, key informant
      interviews, and focus group discussions were evaluated to compare patient/CHW
      core demographics, and contrast patient-identified healthcare needs against CHW
      identified cCHW service capabilities. Quantitative data were evaluated
      descriptively and bi-variably using two-sample independent t tests and Pearson's
      Chi square tests. Qualitative data were coded for emerging themes using a priori
      and standard grounded theory methods. Patients and CHWs were significantly
      similar in age, education, and income, but significantly differed in gender,
      race, United States generation, and marital status. For all healthcare-related
      services in which patients and CHWs exhibited significant differences, the odds
      CHWs perceived themselves capable of performing services were greater than
      patients' stated need of services. Patients and CHWs overlapped regarding their
      expectations of cCHWs. Although patients and CHWs differed somewhat, they shared
      many of the same expectations for cCHW integration. This information is critical
      to further contextualize cCHW training programs and emphasizes the need to
      education patients about this exciting new form of healthcare delivery. The
      active role of cCHWs in the clinical care team and the community may expand
      patient access to preventive healthcare, improve care quality, and minimize
      health inequities.

PMID- 30101386
TI  - Moderators of Establishing a Smoke-Free Home: Pooled Data from Three Randomized
      Controlled Trials of a Brief Intervention.
AB  - Interventions to create smoke-free homes typically focus on parents, involve
      multiple counseling sessions and blend cessation and smoke-free home messages.
      Smoke-Free Homes: Some Things are Better Outside is a minimal intervention
      focused on smokers and nonsmokers who allow smoking in the home, and emphasizes
      creation of a smoke-free home over cessation. The purpose of this study is to
      conduct moderator analyses using pooled data from three randomized controlled
      trials of the intervention conducted in collaboration with 2-1-1 contact centers
      in Atlanta, North Carolina and Houston. 2-1-1 is a strategic partner for tobacco
      control as it connects over 15 million clients, largely socio-economically
      disadvantaged, to social and health resources each year. A total of 1506 2-1-1
      callers participated across the three intervention trials. Outcomes from 6 months
      intent-to-treat analyses were used to examine whether sociodemographic variables
      and smoking-related characteristics moderated effectiveness of the intervention
      in establishing full home smoking bans. Intervention effectiveness was not
      moderated by race/ethnicity, education, income, children in the home or number of
      smokers in the home. Smoking status of the participant, however, did moderate
      program effectiveness, as did time to first cigarette. Number of cigarettes per
      day and daily versus nondaily smoking did not moderate intervention
      effectiveness. Overall, the intervention was effective across socio-demographic
      groups and was effective without respect to daily versus nondaily smoking or
      number of cigarettes smoked per day, although smoking status and level of
      nicotine dependence did influence effectiveness.

PMID- 30101387
TI  - A phase Ib study of BGJ398, a pan-FGFR kinase inhibitor in combination with
      imatinib in patients with advanced gastrointestinal stromal tumor.
AB  - : Background Preclinical studies suggest that imatinib resistance in
      gastrointestinal stromal tumor (GIST) can be mediated by MAP-kinase activation
      via fibroblast growth factor (FGF) signaling. In FGF stimulated GIST cell lines,
      BGJ398, a pan-FGFR kinase inhibitor in combination with imatinib, was cytotoxic
      and superior to imatinib therapy alone. In FGF-dependent GIST, the combination of
      BGJ398 and imatinib may provide a mechanism to overcome imatinib resistance.
      Methods This phase Ib study of BGJ398 and imatinib was performed in patients with
      imatinib refractory advanced GIST. A standard 3 + 3 dosing schema was utilized to
      determine the recommended phase II dose (RP2D). Two treatment schedules were
      evaluated incorporating imatinib 400 mg daily in combination with (A) BGJ398
      daily 3 weeks on, 1 week off or (B) BGJ398 daily 1 week on, 3 weeks off. Results
      16 patients enrolled. The median age was 54 years (range: 44-77), 81% were male,
      and the median number of lines of prior therapy was 4 [range: 2-6, 13 patients
      had >=3 prior therapies]. 12 patients received treatment on schedule A [BGJ398
      dose range: 25 - 75 mg]: 2 patients experienced dose limiting toxicities (DLT) (n
      = 1, myocardial infarction & grade (G)4 CPK elevation; n = 1, G3 ALT elevation)
      on schedule A (BGJ398 75 mg), significant hyperphosphatemia, an on-target effect,
      was not observed, implying the maximum tolerated dose was below the therapeutic
      dose. Following protocol amendment, 4 patients enrolled on schedule B [BGJ398
      dose range: 75 - 100 mg]: no DLTs were observed. The most common treatment
      related adverse events occurring in >15% of patients included CPK elevation
      (50%), lipase elevation (44%), hyperphosphatemia (24%), anemia (19%), and
      peripheral edema (19%). Among the 12 evaluable patients, stable disease (SD) was
      the best response observed in 7 patients by RECIST v1.1 and 9 patients by CHOI.
      Stable disease >= 32 weeks was observed in 3 patients (25%). Median progression
      free survival was 12.1 weeks (95% CI 4.7-19.5 weeks). Conclusions Toxicity was
      encountered with the combination therapy of BGJ398 and imatinib. Due to
      withdrawal of sponsor support the study closed before the RP2D or dosing schedule
      of the combination therapy was identified. In heavily pre-treated patients,
      stable disease >= 32 weeks was observed in 3 of 12 evaluable patients. TRIAL
      REGISTRATION: NCT02257541 .

PMID- 30101388
TI  - The Monocarboxylate transporter inhibitor Quercetin induces intracellular
      acidification in a mouse model of Glioblastoma Multiforme: in-vivo detection
      using magnetic resonance imaging.
AB  - The response of tumor intracellular pH to a pharmacological challenge could help
      identify aggressive cancer. Chemical exchange saturation transfer (CEST) is an
      MRI contrast mechanism that is dependent on intracellular pH (pHi). pHi is
      important in the maintenance of normal cell function and is normally maintained
      within a narrow range by the activity of transporters located at the plasma
      membrane. In cancer, changes in pHi have been correlated with both cell
      proliferation and cell death. Quercetin is a bioflavonoid and monocarboxylate
      transporter (MCT) inhibitor. Since MCTs plays a significant role in maintaining
      pH balance in the tumor microenvironment, we hypothesized that systemically
      administered quercetin could selectively acidify brain tumors. The goals of the
      current study were to determine whether CEST MRI measurements sensitive to tumor
      pH could detect acidification after quercetin injection and to measure the
      magnitude of the pH change (DeltapH). Using a 9.4 T MRI, amine and amide
      concentration independent detection (AACID) CEST spectra were acquired in six
      mice approximately 15 +/- 1 days after implanting 105 U87 human glioblastoma
      multiforme cells in the brain, before and after administration of quercetin
      (dose: 200 mg/kg) by intraperitoneal injection. Three additional mice were
      studied as controls and received only vehicle dimethyl sulfoxide (DMSO)
      injection. Repeated measures t-test was used to compare AACID changes in tumor
      and contralateral tissue regions of interest. Two hours after quercetin injection
      there was a significant increase in tumor AACID by 0.07 +/- 0.03 corresponding to
      a 0.27 decrease in pHi, and no change in AACID in contralateral tissue. There was
      also a small average increase in AACID in tumors within the three mice injected
      with DMSO only. The use of the natural compound quercetin in combination with pH
      weighted MRI represents a unique approach to cancer detection that does not
      require injection of an imaging contrast agent.

PMID- 30101389
TI  - Preoperative predictors of difficult hypopharyngeal exposure by retractor for
      transoral robotic surgery.
AB  - INTRODUCTION: Transoral endoscopic surgeries provide excellent oncologic outcomes
      while preserving speech and swallowing ability. However, feasibility has been a
      major concern about transoral surgery. Therefore, ensuring visualization of the
      surgical field and sufficient working space is required. The aim of this study
      was to evaluate the parameters in the preoperative assessment that affect
      hypopharyngeal exposure. METHODS: Before transoral surgery, parameters regarding
      the patient's neck and face such as modified Mallampati index, thyroid-mental
      distance (TMD), and ability to fully open the mouth were evaluated. Cephalometry
      and cervical spine radiography were performed preoperatively to evaluate the size
      of the mandible bone, mouth opening, and cervical spine extension. Mandibular
      bone parameters such as intergonion distance, mental-gonion distance, articulare
      gonion distance, and aperture angle were measured. According to hypopharyngeal
      exposure using FKWO retractor, patients were divided into difficult
      hypopharyngeal exposure group (DHE) and non-difficult hypopharyngeal exposure
      group (non-DHE). Parameters were enrolled to evaluate the relationship between
      these parameters and DHE status. RESULTS: This study included 51 patients, 37 in
      the non-DHE group and 14 in the DHE group. On radiographic evaluation, there was
      a significant difference in the degree of cervical lordosis between non-DHE and
      DHE patients. A significantly higher proportion of DHE patients had a history of
      radiotherapy compared with non-DHE patients. CONCLUSION: Patients with limited
      cervical extension and a history of previous radiotherapy might have difficult
      hypopharyngeal exposure during transoral surgery. This is the first report to
      suggest a classification system for hypopharyngeal exposure during transoral
      surgery.

PMID- 30101390
TI  - Correction to: Propofol: A Review of its Role in Pediatric Anesthesia and
      Sedation.
AB  - The original article can be found online.

PMID- 30101391
TI  - Vascular responses to abrupt blood flow change after bypass surgery for complex
      intracranial aneurysms.
AB  - BACKGROUND: Bypass surgery for complex intracranial aneurysms (IAs) results in
      drastic blood flow changes in intracranial arteries. The aim of the study was to
      elucidate how vessels adapt to blood flow changes after bypass surgery with phase
      contrast magnetic resonance imaging (PC-MRI). METHODS: This is a prospective
      observational study to assess changes of the blood flow in intracranial arteries
      after bypass surgery for IAs. Flow rates and vessel diameters were measured with
      PC-MRI in 52 intracranial arteries of 7 healthy volunteers and 31 arteries of 8
      IA patients who underwent bypass surgery. Wall shear stress (WSS) was calculated
      with the Hagen-Poiseuille formula. In 18 arteries of 5 patients, the same
      measurement was performed 1, 3, and 12 months after surgery. RESULTS: PC-MRI
      showed a strong positive correlation between the flow rate and the third power of
      vessel diameter in both healthy volunteers (r = 0.82, P < 0.0001) and IA patients
      (r = 0.90, P < 0.0001), indicating the constant WSS. Of the 18 arteries in 5
      patients, WSS increased in 7 arteries and decreased in 11 arteries immediately
      after surgery. In the WSS-increased group, WSS returned to the preoperative value
      in the third postoperative month. In the WSS-decreased group, WSS increased in
      the 12th month, but did not return to the preoperative level. CONCLUSIONS: In a
      physiological state, WSS was constant in intracranial arteries. Changed WSS after
      bypass surgery tended to return to the preoperative value, suggesting that vessel
      diameter and flow rate might be controlled so that WSS remains constant.

PMID- 30101392
TI  - Prognostic value of volume-based metabolic parameters of 18F-FDG PET/CT in
      ovarian cancer: a systematic review and meta-analysis.
AB  - OBJECTIVE: To perform a systematic review and meta-analysis on the prognostic
      value of 18F-FDG PET-derived volume-based parameters regarding metabolic tumor
      volume (MTV) and total lesion glycolysis (TLG) in patients with ovarian cancer.
      METHODS: Pubmed and EMBASE databases were searched up to February 12, 2018 for
      studies which evaluated MTV or TLG as a prognostic factor in ovarian cancer with
      progression-free (PFS) and overall survival (OS) as the endpoints. Hazard ratios
      (HRs) were meta-analytically pooled using the random-effects model. Multiple
      subgroup analyses based on clinicopathological and PET variables were performed.
      RESULTS: Eight studies with 473 patients were included. The pooled HRs of MTV and
      TLG for PFS were 2.50 (95% CI 1.79-3.48; p < 0.00001) and 2.42 (95% CI 1.61-3.65;
      p < 0.0001), respectively. Regarding OS, the pooled HRs of MTV and TLG were 8.06
      (95% CI 4.32-15.05; p < 0.00001) and 7.23 (95% CI 3.38-15.50; p < 0.00001),
      respectively. Multiple subgroup analyses consistently showed that MTV and TLG
      were significant prognostic factors for PFS with pooled HRs ranging from 2.35 to
      2.58 and from 1.73 to 3.35, respectively. CONCLUSIONS: MTV and TLG from 18F-FDG
      PET were significant prognostic factors in patients with ovarian cancer. Despite
      the clinical heterogeneity and difference in methodology between the studies,
      patients with a high MTV or TLG have a higher risk of disease progression or
      death.

PMID- 30101394
TI  - Low-Intensity Outreach to Increase Uptake of HIV Preexposure Prophylaxis Among
      Patients with Sexually Transmitted Infections.
AB  - We piloted a low-intensity outreach intervention to increase linkage to PrEP care
      among HIV-uninfected individuals with rectal sexually transmitted infections or
      syphilis. We sent a secure email message or letter with information about
      accessing PrEP. Of those sent an email, 12.4% were linked to PrEP care; linkage
      differed by race/ethnicity, ranging from 0% of Black individuals to 32% of
      Hispanic individuals (P = 0.019). No individuals sent letters were linked to PrEP
      care. A one-time secure email to high-risk patients is feasible to increase
      linkage to PrEP care. Studies are needed to evaluate scalable interventions to
      increase PrEP uptake in at-risk populations.

PMID- 30101395
TI  - Nurturing Our Better Nature: A Proposal for Cognitive Integrity as a Foundation
      for Autonomous Living.
AB  - As we account for the genetic and environmental influences on morally-relevant
      character traits like intellectual honesty, industriousness, and self-control, do
      we risk becoming ever less accountable to ourselves? Behavioral genetic research
      suggests that about half the variance in such character traits is likely
      attributable to heredity, and a small fraction to the shared family environment.
      The remaining 40-60% is explained by neither genes nor family upbringing. This
      raises the question: how active a role can individuals play in shaping their own
      character? What, if anything, can and should one do to take responsibility for
      the kind of person one becomes? This paper sketches a novel theoretical proposal
      for addressing these questions, by drawing on several previously disparate lines
      of research within behavior genetics, philosophy, and experimental psychology.
      Our core proposal concerns the metacognitive capacity to engage in active,
      reality-based cognition, as opposed to passive, stimulus-driven processing or an
      active pretense at cognition (i.e., self-deception). We review arguments and
      evidence indicating that human beings both can and should exercise this capacity,
      which we have termed "cognitive integrity." We argue that doing so can in a
      certain sense "set us free" of our genetic and environmental influences-not by
      rendering them irrelevant, but by giving us the awareness and motivation to
      manage them more responsibly. This perspective has important implications for
      guiding the development of psychosocial interventions, and for informing how we
      direct ourselves more generally, both as individuals and as a society.

PMID- 30101397
TI  - A comprehensive review on current status, mechanism, and possible sources of
      arsenic contamination in groundwater: a global perspective with prominence of
      Pakistan scenario.
AB  - Arsenic(As)-mediated contamination of groundwater resources in different parts of
      the world is a consequence of natural or anthropogenic sources, leading to
      adverse effects on the environment and human health. Millions of people from
      different countries are unfortunately consuming groundwater contaminated with
      alarming levels of As. Exposure to the high concentration of As for an extended
      period of time can cause devastating effects on human health such as skin
      lesions, cardiac disorders, discolouration and cancer. Until 2018, about 11
      districts of Sindh and Punjab provinces in Pakistan had been found with As
      contamination in groundwater beyond the national defined permissible level, i.e.
      50 ug/L. Tharparkar and Hyderabad (in Sindh province) along Indus river and
      Lahore and Kasur (in Punjab province) are well-known hotspots sites of natural
      geogenic As contamination in groundwater. Higher levels of Sulfates (SO42-),
      Chloride (Cl-) and Carbonate (CO32-) along with the elevated values of electrical
      conductivity and basic pH, as well as augmented presence of "As V" species, were
      all an indication of oxidizing condition in groundwater, and these oxidizing
      conditions are identified as the primary mechanism of As contamination into
      aquifers of Pakistan via oxidative dissolution. The main aim of this review is to
      summarize and discuss the current contamination status of As in groundwater water
      globally with a special focus on Pakistan scenario, isotopic evidence to track
      sources of groundwater recharge and its effects on As contamination in
      groundwater with various redox conditions prevailing in Pakistan. In addition,
      public health consequences of As contamination and mitigation strategies for As
      removal from water resources have been also highlighted. In this review, the data
      were extracted from various cutting edge studies published in national and
      international journals.

PMID- 30101396
TI  - Response to "Comments on 'Novel real-time tumor-contouring method using deep
      learning to prevent mistracking in X-ray fluoroscopy"'.

PMID- 30101398
TI  - Complex hydrochemical characteristics of the Middle-Upper Pleistocene aquifer in
      Soc Trang Province, Southern Vietnam.
AB  - Environmental isotope techniques were applied to study the hydrochemical
      characteristics of groundwater in Soc Trang Province, Southern Vietnam, in frame
      of the project Improvement of Groundwater Protection in Vietnam (IGPVN).
      Groundwater samples were collected from various monitoring wells (newly drilled
      by the IGPVN project), national monitoring wells, private tube wells and
      production wells. Surface water samples were collected from rivers, ponds or
      canals. The aquifer system is more complex than presumed as the hydrochemical and
      stable isotope compositions of groundwater samples in the Middle-Upper
      Pleistocene (qp2-3) aquifer differ significantly in lateral direction.
      Furthermore, observed changing redox reactions within the target aquifer from dry
      to wet season make it probable that some interaction with overlying aquifers
      exists. The stable isotope signatures of the qp2-3 groundwater samples can be
      divided into two distinct groups which, respectively, originated from paleo
      meteoric water and either was located in paleo-salinized areas of the qp2-3
      aquifer or resulted from evaporation effect of recharging water prior or during
      infiltration process. In fact, individual parts of "the same" aquifer seem not to
      be hydraulically connected to each other. The environmental isotope data provided
      neither evidences of hydraulic connection between the rivers and the qp2-3
      aquifer nor of recent groundwater recharge in the Province. As a result,
      saltwater from the sea intruded inland to some extent via the Hau River during
      the dry season, but it did not affect the target aquifer. Any recharge from
      surface water to the qp2-3 aquifer in Soc Trang should occur outside the
      boundaries of Soc Trang Province. Considering the low groundwater transit
      velocities roughly estimated in this study (3.6 m/year and 7.8 m/year), it may
      take several ten thousands to hundred thousands of years for recharging water
      from beyond the Vietnam's national border to reach the qp2-3 aquifer in Soc Trang
      Province. Consequently, natural recharge cannot help to reduce groundwater
      declining in the short-to-middle term.

PMID- 30101401
TI  - Comment on "Do hospital doctors test for thrombophilia in patients with venous
      thromboembolism?"

PMID- 30101400
TI  - Midpalatal suture: evaluation of the morphological maturation stages via bone
      density.
AB  - BACKGROUND: To investigate the relationship between the morphological maturation
      stages of the midpalatal suture and its bone densities. METHODS: The sample
      consisted of 91 subjects aged 8-18 years who underwent cone beam computed
      tomography. All images were examined to classify morphological maturation of the
      midpalatal suture to five groups according to Angelieri et al. Bone density of
      the midpalatal suture was measured at the maxillary and palatal regions. Kruskal
      Wallis and Mann-Whitney U tests were used to analyze the difference between
      groups. RESULTS: Bone density of the midpalatal suture was significantly higher
      in the palatal region in E stage and in the maxillary region in D and E stages.
      CONCLUSIONS: It is concluded that the change in bone density of the midpalatal
      suture between the morphological maturation stages supports their reliability in
      clinical application.

PMID- 30101399
TI  - A deep convolutional neural network approach for predicting phenotypes from
      genotypes.
AB  - MAIN CONCLUSION: Deep learning is a promising technology to accurately select
      individuals with high phenotypic values based on genotypic data. Genomic
      selection (GS) is a promising breeding strategy by which the phenotypes of plant
      individuals are usually predicted based on genome-wide markers of genotypes. In
      this study, we present a deep learning method, named DeepGS, to predict
      phenotypes from genotypes. Using a deep convolutional neural network, DeepGS uses
      hidden variables that jointly represent features in genotypes when making
      predictions; it also employs convolution, sampling and dropout strategies to
      reduce the complexity of high-dimensional genotypic data. We used a large GS
      dataset to train DeepGS and compared its performance with other methods. The
      experimental results indicate that DeepGS can be used as a complement to the
      commonly used RR-BLUP in the prediction of phenotypes from genotypes. The
      complementarity between DeepGS and RR-BLUP can be utilized using an ensemble
      learning approach for more accurately selecting individuals with high phenotypic
      values, even for the absence of outlier individuals and subsets of genotypic
      markers. The source codes of DeepGS and the ensemble learning approach have been
      packaged into Docker images for facilitating their applications in different GS
      programs.

PMID- 30101402
TI  - Treatment of Complications from Immune Checkpoint Inhibition in Patients with
      Lung Cancer.
AB  - OPINION STATEMENT: Immune checkpoint inhibitors have revolutionized the
      management of advanced NSCLC. With the intention of generating an anti-tumor
      immune response, ICIs can also lead to inflammatory side effects involving a wide
      variety of organs in the body, termed immune-related adverse events. Although no
      prospective clinical trial exists to guide recommendations for optimal and more
      specific immunosuppressive treatments rather than corticosteroids, further
      studies may lead to a more mechanistic-based approach towards these toxicities in
      the future. In relation to current practice, we recommend adherence to the recent
      published guidelines which emphasize the importance of early recognition and
      administration of temporary immunosuppressive therapy with corticosteroids in
      most cases, depending on the organ system involved, and the severity of toxicity.
      Recognition of these toxicities is increasingly important as the use of these
      agents expand within different indications for patients with lung cancers, and to
      other tumor types.

PMID- 30101404
TI  - Correction to: Cell dynamics during differentiation therapy with all-trans
      retinoic acid in acute promyelocytic leukemia.
AB  - In the original publication of the article, Table 2 was published incorrectly.
      The column names were swapped under the column heading "Prom (%)". The correct
      column names are PB and BM.

PMID- 30101403
TI  - Evidence of genetically diverse virulent mating types of Phytophthora capsici
      from Capsicum annum L.
AB  - Chili pepper (Capsicum annum L.) is an important economic crop that is severely
      destroyed by the filamentous oomycete Phytophthora capsici. Little is known about
      this pathogen in key chili pepper farms in Punjab province, Pakistan. We
      investigated the genetic diversity of P. capsici strains using standard taxonomic
      and molecular tools, and characterized their colony growth patterns as well as
      their disease severity on chili pepper plants under the greenhouse conditions.
      Phylogenetic analysis based on ribosomal DNA (rDNA), beta-tubulin and translation
      elongation factor 1alpha loci revealed divergent evolution in the population
      structure of P. capsici isolates. The mean oospore diameter of mating type A1
      isolates was greater than that of mating type A2 isolates. We provide first
      evidence of an uneven distribution of highly virulent mating type A1 and A2 of P.
      capsici that are insensitive to mefenoxam, pyrimorph, dimethomorph, and
      azoxystrobin fungicides, and represent a risk factor that could ease outpacing
      the current P. capsici management strategies.

PMID- 30101407
TI  - Invasive Pulmonary Aspergillosis Complicated by Carbapenem-Resistant Pseudomonas
      aeruginosa Infection During Pembrolizumab Immunotherapy for Metastatic Lung
      Adenocarcinoma: Case Report and Review of the Literature.
AB  - The widespread use of T lymphocyte-associated antigen-4 (CTLA-4) and programmed
      death (PD)-1 and PD ligand-1 (PDL1)-targeted agents in cancer patients as
      immunotherapy has raised some issues on their safety profile. Regarding
      infectious complications, it has emerged that these compounds do not
      intrinsically increase susceptibility to opportunistic infections, which mainly
      correlate with the co-administration of systemic immunosuppressive therapy (high
      dose corticosteroids and anti-tumor necrosis factors inhibitors) to cure immune
      related adverse events (colitis, hepatitis, pneumonitis and pancreatitis), well
      known complications of these targeted drugs. These observations lead experts'
      opinion to suggest primary anti-Pneumocystis prophylaxis in patients undergoing
      CTLA-4 and PD-1/PDL1 agents who will receive prednisone 20 mg daily for >= 4
      weeks. Few data on invasive fungal infections in this context are available. We
      report here a case of probable invasive pulmonary aspergillosis (p-IPA)
      complicating first-line immunotherapy with pembrolizumab for metastatic lung
      cancer that was further aggravated by multidrug-resistant Pseudomonas aeruginosa
      superinfection of fungal cavities; the patient received concurrent systemic
      corticosteroid therapy as anti-edema treatment for cerebral metastases. Reviewing
      literature about Aspergillus diseases in subjects receiving CTLA-4 and PD-1 and
      PDL1-targeted agents, we found three cases of invasive aspergillosis and one case
      of exacerbation of chronic progressive pulmonary aspergillosis after nivolumab
      treatment; to the best of our knowledge, this is the first report of p-IPA
      complicating pembrolizumab immunotherapy. Briefly, in this new setting of
      biological/targeted drugs, waiting for growing clinical experience, we recommend
      a high level of alertness in diagnosing any infectious complications.

PMID- 30101405
TI  - Implication of gut microbiota metabolites in cardiovascular and metabolic
      diseases.
AB  - Evidence from the literature keeps highlighting the impact of mutualistic
      bacterial communities of the gut microbiota on human health. The gut microbita is
      a complex ecosystem of symbiotic bacteria which contributes to mammalian host
      biology by processing, otherwise, indigestible nutrients, supplying essential
      metabolites, and contributing to modulate its immune system. Advances in
      sequencing technologies have enabled structural analysis of the human gut
      microbiota and allowed detection of changes in gut bacterial composition in
      several common diseases, including cardiometabolic disorders. Biological signals
      sent by the gut microbiota to the host, including microbial metabolites and pro
      inflammatory molecules, mediate microbiome-host genome cross-talk. This rapidly
      expanding line of research can identify disease-causing and disease-predictive
      microbial metabolite biomarkers, which can be translated into novel biodiagnostic
      tests, dietary supplements, and nutritional interventions for personalized
      therapeutic developments in common diseases. Here, we review results from the
      most significant studies dealing with the association of products from the gut
      microbial metabolism with cardiometabolic disorders. We underline the importance
      of these postbiotic biomarkers in the diagnosis and treatment of human disorders.

PMID- 30101409
TI  - Is every woven coronary artery benign? Case report.

PMID- 30101408
TI  - Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a food allergen-induced inflammatory disorder.
      EoE is increasingly recognized as a cause of swallowing dysfunction, food
      impaction and esophageal stricture. Inflammation of the esophageal mucosa
      involves immune cell infiltrate, reactive epithelial changes and fibroblast
      activation, culminating in robust tissue remodeling toward esophageal fibrosis
      characterized by excess collagen deposition in the subepithelial lamina propria.
      Fibrosis contributes to a unique mechanical property of the EoE-affected
      esophagus that is substantially stiffer than the normal esophagus. There is a
      great need to better understand the processes behind esophageal fibrosis in order
      to foster improved diagnostic tools and novel therapeutics for EoE-related
      esophageal fibrosis. In this review, we discuss the role of esophageal
      inflammatory microenvironment that promotes esophageal fibrosis, with specific
      emphasis upon cytokines-mediated functional epithelial-stromal interplays,
      recruitment and activation of a variety of effector cells, and tissue stiffness.
      We then explore the current state of clinical methodologies to detect and treat
      the EoE-related esophageal stricture.

PMID- 30101410
TI  - Drug-free microneedles in the treatment of keloids: a single-blinded
      intraindividual controlled clinical trial.

PMID- 30101411
TI  - The gracilis muscle flap for irreparable, "impossible", and recurrent obstetric
      fistulas.

PMID- 30101412
TI  - A Multicenter, Prospective, Observational Study to Determine Predictive Factors
      for Multidrug-Resistant Pneumonia in Critically Ill Adults: The DEFINE Study.
AB  - OBJECTIVE: This study was conducted to describe the prevalence, epidemiology, and
      clinical outcomes of multidrug-resistant (MDR) organism (MDRO) pneumonia in
      critically ill patients. METHODS: A multicenter, prospective, observational study
      of patients admitted to 60 intensive care units (ICUs), from 34 hospitals, in the
      United States from November to December 2016. Adults (> 18 yrs) receiving
      antimicrobial therapy at least 5 days for pneumonia were included. Patients were
      classified into two categories, with or without MDRO, and subcategorized by
      pneumonia type. MEASUREMENTS AND MAIN RESULTS: Demographics, medication
      histories, and health care exposure were collected during ICU admission and
      compared using t test and chi-square tests. Multivariate logistic regression was
      used to determine predictive factors for MDRO pneumonia and hospital mortality.
      Of 652 patients, 92 patients (14.1%) developed MDR pneumonia. Predictors of MDRO
      pneumonia were acid suppression therapy within the previous 90 days (odds ratio
      [OR] 1.88 [1.14-3.09]; p=0.013), mechanical ventilation (OR 1.96 [1.14-3.35];
      p<0.001), and history of MDRO infection (OR 4.74 [2.21-10.18]; p<0.001).
      Appropriate initial antimicrobial selection occurred in 58 patients (63%) with
      MDRO pneumonia compared to 464 patients (82.7%) in patients without MDRO
      pneumonia (p<0.001). MDRO pneumonia was not associated with hospital mortality
      (18.5% vs 17.6%, p=0.087). CONCLUSIONS: In a broad cohort of critically ill
      patients, MDRO pneumonia is infrequent, and associated with factors describing
      the intensity of health care provided. Presence of MDRO pneumonia is not
      associated with hospital mortality. Further study is needed to clarify risk
      factors for multidrug-resistant pneumonia in critically ill patients.

PMID- 30101413
TI  - Three-dimensional printing with nano-enabled filaments releases polymer particles
      containing carbon nanotubes into air.
AB  - Fused deposition modeling (FDMTM) 3-dimensional printing uses polymer filament to
      build objects. Some polymer filaments are formulated with additives, though it is
      unknown if they are released during printing. Three commercially available
      filaments that contained carbon nanotubes (CNTs) were printed with a desktop
      FDMTM 3-D printer in a chamber while monitoring total particle number
      concentration and size distribution. Airborne particles were collected on filters
      and analyzed using electron microscopy. Carbonyl compounds were identified by
      mass spectrometry. The elemental carbon content of the bulk CNT-containing
      filaments was 1.5 to 5.2 wt%. CNT-containing filaments released up to 1010
      ultrafine (d < 100 nm) particles/g printed and 106 to 108 respirable (d ~0.5 to 2
      MUm) particles/g printed. From microscopy, 1% of the emitted respirable polymer
      particles contained visible CNTs. Carbonyl emissions were observed above the
      limit of detection (LOD) but were below the limit of quantitation (LOQ). Modeling
      indicated that, for all filaments, the average proportional lung deposition of
      CNT-containing polymer particles was 6.5%, 5.7%, and 7.2% for the head airways,
      tracheobronchiolar, and pulmonary regions, respectively. If CNT-containing
      polymer particles are hazardous, it would be prudent to control emissions during
      use of these filaments.

PMID- 30101406
TI  - Fibroblast-to-myofibroblast transition in bronchial asthma.
AB  - Bronchial asthma is a chronic inflammatory disease in which bronchial wall
      remodelling plays a significant role. This phenomenon is related to enhanced
      proliferation of airway smooth muscle cells, elevated extracellular matrix
      protein secretion and an increased number of myofibroblasts. Phenotypic
      fibroblast-to-myofibroblast transition represents one of the primary mechanisms
      by which myofibroblasts arise in fibrotic lung tissue. Fibroblast-to
      myofibroblast transition requires a combination of several types of factors, the
      most important of which are divided into humoural and mechanical factors, as well
      as certain extracellular matrix proteins. Despite intensive research on the
      nature of this process, its underlying mechanisms during bronchial airway wall
      remodelling in asthma are not yet fully clarified. This review focuses on what is
      known about the nature of fibroblast-to-myofibroblast transition in asthma. We
      aim to consider possible mechanisms and conditions that may play an important
      role in fibroblast-to-myofibroblast transition but have not yet been discussed in
      this context. Recent studies have shown that some inherent and previously
      undescribed features of fibroblasts can also play a significant role in
      fibroblast-to-myofibroblast transition. Differences observed between asthmatic
      and non-asthmatic bronchial fibroblasts (e.g., response to transforming growth
      factor beta, cell shape, elasticity, and protein expression profile) may have a
      crucial influence on this phenomenon. An accurate understanding and recognition
      of all factors affecting fibroblast-to-myofibroblast transition might provide an
      opportunity to discover efficient methods of counteracting this phenomenon.

PMID- 30101414
TI  - In vitro cytotoxic and antiproliferative effects of usnic acid on hormone
      dependent breast and prostate cancer cells.
AB  - The aim of the current study was first to investigate cytotoxic activity of usnic
      acid (UA) on hormone-dependent breast and prostate cancer, and normal cells.
      Cells were treated with increasing concentrations (25 to 150 uM) of UA for 48
      hours and cell viability, quantitative and morphological analysis of cell death,
      and cell cycle analysis were performed. UA was shown to have selective
      cytotoxicity on hormone-dependent cancer cells with the IC50 levels of 71.4 and
      77.5 uM for MCF7 and LNCaP cells, respectively. UA induced apoptotic cell death
      and G0/G1 cell cycle arrest without damaging normal cells. MCF7 cells were more
      sensitive to UA than LNCaP cells. Our results first revealed that UA is a
      promising candidate as an alternative agent for hormone-dependent breast and
      prostate cancers. However, molecular mechanism underlying the UA-mediated cell
      death in cancer cells should be investigated further.

PMID- 30101415
TI  - Semi-dominant mutation in the cysteine-rich receptor-like kinase gene, ALS1,
      conducts constitutive defence response in rice.
AB  - Plants have evolved a sophisticated two-branch defence system to prevent the
      growth and spread of pathogen infection. The novel Cys-rich repeat (CRR)
      containing receptor-like kinases, known as CRKs, were reported to mediate defence
      resistance in plants. For rice, there are only two reports of CRKs. A semi
      dominant lesion mimic mutant als1 (apoptosis leaf and sheath 1) in rice was
      identified to demonstrate spontaneous lesions on the leaf blade and sheath. A map
      based cloning strategy was used for fine mapping and cloning of ALS1, which was
      confirmed to be a typical CRK in rice. Functional studies of ALS1 were conducted,
      including phylogenetic analysis, expression analysis, subcellular location and
      blast resistance identification. Most pathogenesis-related (PR) genes and other
      defence-related genes were activated and up-regulated to a high degree. ALS1 was
      expressed mainly in the leaf blade and sheath, in which further study revealed
      that ALS1 was present in the vascular bundles. ALS1 was located in the cell
      membrane of rice protoplasts, and its mutation did not change its subcellular
      location. Jasmonic acid (JA) and salicylic acid (SA) accumulation were observed
      in als1, and enhanced blast resistance was also observed. The mutation of ALS1
      caused a constitutively activated defence response in als1. The results of our
      study imply that ALS1 participates in a defence response resembling the common SA
      , JA- and NH1-mediated defence responses in rice.

PMID- 30101416
TI  - Clinical efficacy of a chlorhexidine-based mouthrinse containing hyaluronic acid
      and an antidiscoloration system in patients undergoing flap surgery: A triple
      blind, parallel-arm, randomized controlled trial.
AB  - OBJECTIVES: To evaluate the postsurgery gingival healing as well as plaque,
      gingival inflammation and staining levels following the use of a 0.2%
      chlorhexidine (CHX) solution with or without antidiscoloration system (ADS) and
      0.2% hyaluronic acid (HA). METHODS: Patients undergoing flap surgery at sites
      with an intact or reduced but healthy periodontium participated in a parallel-arm
      RCT. After surgery, patients used the assigned mouthrinse (CHX + HA + ADS or CHX)
      for 21 days. At days 7 and 21, the healing process was evaluated at experimental
      teeth using a composite index, namely the Gingival Healing Index (GHI). GHI score
      was obtained as the sum of the scores related to the severity of wound dehiscence
      (score 1-3) and the profile of the buccal and oral aspects of the papilla (score
      1-3). Therefore, GHI ranged from 2 (worst quality of healing) to 6 (optimal
      quality of healing). Plaque Index (PlI), Gingival Index (GI), angulated bleeding
      score (AngBS), and tooth and tongue staining were also assessed. RESULTS: In both
      groups, GHI assumed values of 5 or 6 at both days 7 and 21 in >=50% of patients,
      and low median values of PlI, GI, AngBS and staining were observed during the 21
      day period. Except for a significantly lower GI in CHX group at day 7, no other
      significant intergroup differences were found. CONCLUSIONS: Postsurgery plaque
      control based on either CHX or CHX + HA + ADS mouthrinses results in optimal
      plaque control and quality of early gingival healing along with limited tooth and
      tongue staining.

PMID- 30101418
TI  - The Way Forward for Mechanism-Based Therapeutics in Genetically Defined
      Neurodevelopmental Disorders.
AB  - Rare genetically defined neurodevelopmental disorders with increased risk of
      autism have recently become an entry point for autism-related drug discovery.
      Through exploration of downstream effects of the pathological mutations, specific
      mechanistic pathways have been identified as dysregulated. The identification of
      shared mechanisms across forms of autism opens the door for the development of
      novel "mechanism-based therapeutics." However, confidence in the therapeutic
      mechanism does not diminish the need for well-designed clinical trials.

PMID- 30101417
TI  - Imine-N-Heterocyclic Carbenes as Versatile Ligands in Ruthenium(II) p-Cymene
      Anticancer Complexes: A Structure-Activity Relationship Study.
AB  - A family of novel imine-N-heterocyclic carbene ruthenium(II) complexes of the
      general formula [(eta6 -p-cymene)Ru(C^N)Cl]PF6 - (where C^N is an imine-N
      heterocyclic carbene chelating ligand with varying substituents) have been
      prepared and characterized. In this imine-N-heterocyclic carbene chelating ligand
      framework, there are three potential sites that can be modified, which
      distinguishes this class of ligand and provides a body of flexibilities and
      opportunities to tune the cytotoxicity of these ruthenium(II) complexes. The
      influence of substituent effects of three tunable domains on the anticancer
      activity and catalytic ability in converting coenzyme NADH to NAD+ is
      investigated. This family of complexes displays an exceedingly distinct
      anticancer activity against A549 cancer cells, despite their close structural
      similarity. Complex 9 shows the highest anticancer activity in this series
      against A549 cancer cells (IC50 =14.36 MUm), with an approximately 1.5-fold
      better activity than the clinical platinum drug cisplatin (IC50 =21.30 MUm) in
      A549 cancer cells. Mechanistic studies reveal that complex 9 mediates cell death
      mainly through cell stress, including cell cycle arrest, inducing apoptosis,
      increasing intracellular reactive oxygen species (ROS) levels, and depolarization
      of the mitochondrial membrane potential (MMP). Furthermore, lysosomal damage is
      also detected by confocal microscopy.

PMID- 30101419
TI  - Opposing roles of CB1 and CB2 cannabinoid receptors in the stimulant and
      rewarding effects of cocaine.
AB  - BACKGROUND AND PURPOSE: The endocannabinoids anandamide and 2
      arachidonoylglycerol (2-AG) bind to CB1 and CB2 cannabinoid receptors in the
      brain and modulate the mesolimbic dopaminergic pathway. This neurocircuitry is
      engaged by psychostimulant drugs, including cocaine. Although CB1 receptor
      antagonism and CB2 receptor activation are known to inhibit certain effects of
      cocaine, they have been investigated separately. Here, we tested the hypothesis
      that there is a reciprocal interaction between CB1 receptor blockade and CB2
      receptor activation in modulating behavioural responses to cocaine. EXPERIMENTAL
      APPROACH: Male Swiss mice received i.p. injections of cannabinoid-related drugs
      followed by cocaine, and were then tested for cocaine-induced hyperlocomotion, c
      Fos expression in the nucleus accumbens and conditioned place preference. Levels
      of endocannabinoids after cocaine injections were also analysed. KEY RESULTS: The
      CB1 receptor antagonist, rimonabant, and the CB2 receptor agonist, JWH133,
      prevented cocaine-induced hyperlocomotion. The same results were obtained by
      combining sub-effective doses of both compounds. The CB2 receptor antagonist,
      AM630, reversed the inhibitory effects of rimonabant in cocaine-induced
      hyperlocomotion and c-Fos expression in the nucleus accumbens. Selective
      inhibitors of anandamide and 2-AG hydrolysis (URB597 and JZL184, respectively)
      failed to modify this response. However, JZL184 prevented cocaine-induced
      hyperlocomotion when given after a sub-effective dose of rimonabant. Cocaine did
      not change brain endocannabinoid levels. Finally, CB2 receptor blockade reversed
      the inhibitory effect of rimonabant in the acquisition of cocaine-induced
      conditioned place preference. CONCLUSION AND IMPLICATIONS: The present data
      support the hypothesis that CB1 and CB2 receptors work in concert with opposing
      functions to modulate certain addiction-related effects of cocaine.

PMID- 30101420
TI  - The simultaneous assessment of and relations between children's sympathetic and
      parasympathetic psychophysiology and their reactive and proactive aggression.
AB  - The goal of the current study was to examine the link between children's
      psychophysiology and aggression when both constructs were assessed simultaneously
      in scenarios designed to provide the opportunity to aggress for either a reactive
      reason or a proactive reason. Both sympathetic nervous system (SNS) activity
      (skin conductance) and parasympathetic nervous system (PNS) activity (respiratory
      sinus arrhythmia or RSA), as well as their interaction, were included as
      physiological measures. Participants were 35 5th-grade children who were placed
      in two virtual-peer scenarios; one scenario provided the opportunity to aggress
      in response to peer provocation (i.e., reactive aggression) and the other
      scenario provided the opportunity to aggress for instrumental gain (i.e.,
      proactive aggression). Both skin conductance and RSA were assessed at the time
      that children were given the opportunity to aggress; this simultaneous assessment
      of psychophysiology and aggression allowed for an examination of in-the-moment
      relations between the two constructs. For the reactive scenario, RSA moderated
      the in-the-moment relation between skin conductance and aggression such that the
      association was positive at low RSA but negative at high RSA. For the proactive
      scenario, skin conductance negatively predicted aggression in-the-moment, and RSA
      positively predicted aggression in-the-moment, but their interaction was not a
      significant predictor of aggression. Theoretical implications for reactive and
      proactive aggression and underlying physiological processes are discussed.

PMID- 30101421
TI  - An approximate Bayesian significance test for genomic evaluations.
AB  - Genomic information can be used to study the genetic architecture of some trait.
      Not only the size of the genetic effect captured by molecular markers and their
      position on the genome but also the mode of inheritance, which might be additive
      or dominant, and the presence of interactions are interesting parameters. When
      searching for interacting loci, estimating the effect size and determining the
      significant marker pairs increases the computational burden in terms of speed and
      memory allocation dramatically. This study revisits a rapid Bayesian approach
      (fastbayes). As a novel contribution, a measure of evidence is derived to select
      markers with effect significantly different from zero. It is based on the
      credibility of the highest posterior density interval next to zero in a
      marginalized manner. This methodology is applied to simulated data resembling a
      dairy cattle population in order to verify the sensitivity of testing for a given
      range of type-I error levels. A real data application complements this study.
      Sensitivity and specificity of fastbayes were similar to a variational Bayesian
      method, and a further reduction of computing time could be achieved. More than
      50% of the simulated causative variants were identified. The most complex model
      containing different kinds of genetic effects and their pairwise interactions
      yielded the best outcome over a range of type-I error levels. The validation
      study showed that fastbayes is a dual-purpose tool for genomic inferences - it is
      applicable to predict future outcome of not-yet phenotyped individuals with high
      precision as well as to estimate and test single-marker effects. Furthermore, it
      allows the estimation of billions of interaction effects.

PMID- 30101422
TI  - Photosynthetic Bioelectronic Sensors for Touch Perception, UV-Detection, and
      Nanopower Generation: Toward Self-Powered E-Skins.
AB  - Energy self-sufficiency is an inspirational design feature of biological systems
      that fulfills sensory functions. Plants such as the "touch-me-not" and "Venus
      flytrap" not only sustain life by photosynthesis, but also execute specialized
      sensory responses to touch. Photosynthesis enables these organisms to sustainably
      harvest and expend energy, powering their sensory abilities. Photosynthesis
      therefore provides a promising model for self-powered sensory devices like
      electronic skins (e-skins). While the natural sensory abilities of human skin
      have been emulated in man-made materials for advanced prosthetics and soft
      robotics, no previous e-skin has incorporated phototransduction and photosensory
      functions that could extend the sensory abilities of human skin. A proof-of
      concept bioelectronic device integrated with natural photosynthetic pigment
      proteins is presented that shows the ability to sense not only touch stimuli
      (down to 3000 Pa), but also low-intensity ultraviolet radiation (down to 0.01 mW
      cm-2 ) and generate an electrical power of ~260 nW cm-2 . The scalability of this
      device is demonstrated through the fabrication of flexible, multipixel,
      bioelectronic sensors capable of touch registration and tracking. The polysensory
      abilities, energy self-sufficiency, and additional nanopower generation exhibited
      by this bioelectronic system make it particularly promising for applications like
      smart e-skins and wearable sensors, where the photogenerated power can enable
      remote data transmission.

PMID- 30101423
TI  - Long-Life Lithium-Sulfur Batteries with a Bifunctional Cathode Substrate
      Configured with Boron Carbide Nanowires.
AB  - Developing high-energy-density lithium-sulfur (Li-S) batteries relies on the
      design of electrode substrates that can host a high sulfur loading and still
      attain high electrochemical utilization. Herein, a new bifunctional cathode
      substrate configured with boron-carbide nanowires in situ grown on carbon
      nanofibers (B4 C@CNF) is established through a facile catalyst-assisted process.
      The B4 C nanowires acting as chemical-anchoring centers provide strong
      polysulfide adsorptivity, as validated by experimental data and first-principle
      calculations. Meanwhile, the catalytic effect of B4 C also accelerates the redox
      kinetics of polysulfide conversion, contributing to enhanced rate capability. As
      a result, a remarkable capacity retention of 80% after 500 cycles as well as
      stable cyclability at 4C rate is accomplished with the cells employing B4 C@CNF
      as a cathode substrate for sulfur. Moreover, the B4 C@CNF substrate enables the
      cathode to achieve both high sulfur content (70 wt%) and sulfur loading (10.3 mg
      cm-2 ), delivering a superb areal capacity of 9 mAh cm-2 . Additionally, Li-S
      pouch cells fabricated with the B4 C@CNF substrate are able to host a high sulfur
      mass of 200 mg per cathode and deliver a high discharge capacity of 125 mAh after
      50 cycles.

PMID- 30101424
TI  - The RAF-like mitogen-activated protein kinase kinase kinases RAF22 and RAF28 are
      required for the regulation of embryogenesis in Arabidopsis.
AB  - In Arabidopsis, embryonic development follows a stereotypical pattern of cell
      division. Although many factors have been reported to participate in
      establishment of the proper embryonic pattern, the molecular mechanisms
      underlying pattern formation are unclear. In this study we showed that RAF22 and
      RAF28, two RAF-like mitogen-activated protein kinase kinase kinases (MAPKKKs) in
      Arabidopsis, are involved in the regulation of embryogenesis. The double knockout
      mutant of RAF22 and RAF28 was embryo lethal. A large proportion of the raf22-/-
      raf28+/- mutant embryos exhibited various defects, including disordered proembryo
      cell divisions, disruption of the bilaterally symmetrical structure, abnormally
      formative divisions of hypophysis and exaggerated suspensor growth. Whereas the
      kinase active form of RAF22 could complement these embryonic aberrant phenotypes,
      the kinase inactive form could not. The restrictive expression of the basal cell
      fate marker WOX8 in the abnormally dividing suspensor cells and the apical cell
      linage marker WOX2 in the abnormal proembryos indicated that apical and basal
      cell fates were unchanged in the abnormal embryos. The polar distribution of the
      auxin maxima and the PIN1 and PIN7 auxin transporters was markedly altered in the
      abnormal embryos. Our results suggest that RAF22 and RAF28 are important
      components of embryogenesis and that auxin polar transport may be involved in
      this regulation.

PMID- 30101425
TI  - Rapid drink challenge test for the clinical evaluation of patients with
      Achalasia.
AB  - BACKGROUND: Patients with achalasia develop a well-defined obstructive pattern of
      pressure in response to a rapid drink challenge test (RDC). Our aim was to
      determine if successful treatment of achalasia can revert the obstructive pattern
      of pressure in response to the RDC, and if this simple test could be useful in
      the follow-up of patients with achalasia. METHODS: In 26 healthy controls and 103
      patients with achalasia, pressure responses to a RDC were prospectively analysed
      using high resolution esophageal manometry in two consecutive protocols: (a)
      Development study: one RDC was performed in 20 healthy controls, 63 patients with
      nontreated achalasia, and 21 patients with previously treated achalasia; (b)
      Validation study: two RDC were performed before, and 8-12 weeks after treatment,
      in 19 patients with nontreated, newly diagnosed achalasia. KEY RESULTS: In the
      development study no healthy control, 19% of patients with previously treated
      achalasia and 96% of patients with nontreated achalasia developed an obstructive
      pressure pattern during the RDC (P < 0.001). In the validation study, 100% of
      patients had an obstructive pressure pattern before treatment, that reverted to a
      nonobstructive pattern in 89% of patients after treatment (P < 0.001). The
      obstructive pressure pattern during the RDC correlated with clinical symptoms
      (Eckardt score > 3; P < 0.001), and with the height of the water column retained
      after the RDC, as assessed by impedance (P = 0.015). CONCLUSIONS & INFERENCES:
      The RDC may objectively assess treatment outcome in patients with achalasia, and
      can be recommended in the evaluation of achalasia.

PMID- 30101426
TI  - Percentage of ingested sodium excreted in 24-hour urine collections: A systematic
      review and meta-analysis.

PMID- 30101427
TI  - Effects of exogenous methyl jasmonate and salicylic acid on rice resistance to
      Oebalus pugnax.
AB  - BACKGROUND: After herbivore attack, plants express inducible resistance-related
      traits activated by hormones, mainly jasmonic acid (JA) and salicylic acid (SA).
      Methyl jasmonate (MeJa) is a biologically active methyl ester of JA. Exogenous
      applications of JA, SA, and MeJa induce responses similar to herbivory by
      insects. In this study, rice, Oryza sativa L. (Poaceae), plants were treated with
      two concentrations of MeJa (2 and 5 mmol L-1 ), two concentrations of SA (8 and
      16 mmol L-1 ) and herbivory to evaluate effects of elicitation and herbivory on
      resistance to the rice stink bug (RSB) Oebalus pugnax Fabricius, 1775 (Hemiptera:
      Pentatomidae), an injurious insect pest of rice in the United States. RESULTS:
      Nymphs developing on plants treated with SA 16 mmol L-1 took longer to reach
      adulthood than nymphs developing on check plants. Grains per panicle were higher
      in plants treated with SA 16 mmol L-1 and MeJa in both concentrations than in
      check treatment. Plants treated with SA emitted five of six volatile compounds
      identified in equal or higher amounts than plants subjected to previous
      herbivory, particularly methyl salicylate, a known defense-related compound.
      Salicylic acid 16 mmol L-1 was the treatment that elicited the highest amount of
      all volatiles. In the field assay, plots treated with SA 16 mmol L-1 showed lower
      spikelet sterility and a tendency for fewer bugs to be found in plots.
      CONCLUSION: Rice plants possess defense mechanisms that can be elicited using
      hormones as elicitors, mainly SA 16 mmol L-1 , to induce resistance against RSB.
      (c) 2018 Society of Chemical Industry.

PMID- 30101429
TI  - Keratoderma Blenorrhagica.

PMID- 30101428
TI  - The HLA-DRB1*09:29 allele identified in a volunteer donor for hematopoietic stem
      cell transplant.
AB  - HLA-DRB1*09:29 differs from HLA-DRB1*09:01:02:01 in a codon 75 in exon 2.

PMID- 30101430
TI  - Sex-specific additive genetic variances and correlations for fitness in a song
      sparrow (Melospiza melodia) population subject to natural immigration and
      inbreeding.
AB  - Quantifying sex-specific additive genetic variance (VA ) in fitness, and the
      cross-sex genetic correlation (rA ), is prerequisite to predicting evolutionary
      dynamics and the magnitude of sexual conflict. Further, quantifying VA and rA in
      underlying fitness components, and genetic consequences of immigration and
      resulting gene flow, is required to identify mechanisms that maintain VA in
      fitness. However, these key parameters have rarely been estimated in wild
      populations experiencing natural environmental variation and immigration. We used
      comprehensive pedigree and life-history data from song sparrows (Melospiza
      melodia) to estimate VA and rA in sex-specific fitness and underlying fitness
      components, and to estimate additive genetic effects of immigrants alongside
      inbreeding depression. We found evidence of substantial VA in female and male
      fitness, with a moderate positive cross-sex rA . There was also substantial VA in
      male but not female adult reproductive success, and moderate VA in juvenile
      survival but not adult annual survival. Immigrants introduced alleles with
      negative additive genetic effects on local fitness, potentially reducing
      population mean fitness through migration load, but alleviating expression of
      inbreeding depression. Our results show that VA for fitness can be maintained in
      the wild, and be broadly concordant between the sexes despite marked sex-specific
      VA in reproductive success.

PMID- 30101431
TI  - Serum Mac-2 binding protein glycosylation isomer predicts the activation of
      hepatic stellate cells after liver transplantation.
AB  - BACKGROUND AND AIM: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is
      a novel fibrosis marker for various chronic liver diseases. We investigated the
      ability of M2BPGi to predict liver fibrosis in liver transplant (LT) recipients.
      METHODS: A total of 116 liver biopsies were performed in 113 LT recipients. The
      serum level of M2BPGi was also measured on the same day. The median age at LT and
      liver biopsy was 1.1 and 11.8 years, respectively. Serum M2BPGi levels and liver
      fibrosis status using METAVIR fibrosis score were compared. Immunohistological
      evaluation by anti-alpha-smooth-muscle actin (alphaSMA) was performed, and the
      relationship between alphaSMA positive rate and serum M2BPGi levels was
      investigated. RESULTS: The median M2BPGi level was 0.78 (range, 0.22-9.50), and
      65, 29, 16, 5, and 1 patient(s) had METAVIR fibrosis scores of F0, F1, F2, F3,
      and F4, respectively. In patients with F0 fibrosis, median M2BPGi level was 0.69
      and was significantly lower than in patients with F1 (median 0.99, P < 0.01), F2
      (median 1.00, P = 0.01), and F3 fibrosis (median 1.53, P < 0.01). Area-under-the
      curve analysis of the ability of M2BPGi level to predict liver fibrosis grade
      were > F1: 0.716, > F2: 0.720, and > F3: 0.900. Three patients with acute
      cellular rejection showed high levels of M2BPGi, which decreased after the
      treatment. A positive correlation existed between M2BPGi levels and alphaSMA
      positive rate (r2  = 0.715, P < 0.01). CONCLUSION: Mac-2 binding protein
      glycosylation isomer is a novel liver fibrosis marker in LT recipients and is
      also increased in patients with acute liver injuries, especially acute cellular
      rejection, even when fibrosis is absent.

PMID- 30101432
TI  - Mechanochemical Activation of Fluorogenic CuAAC "Click" Reactions for Stress
      Sensing Applications.
AB  - Strategies for visualizing stress within polymeric materials are of growing
      interest during the past decade. In this paper, stress-sensing materials,
      triggered by a mechanoresponsive catalytic system based on latent copper(I)bis(N
      heterocyclic carbene) mechanophores, are reported, which can be activated by
      compression force to trigger a fluorogenic copper(I)-catalyzed alkyne/azide
      "click" cycloaddition reaction, activating a fluorescent dye useful for stress
      sensing applications in bulk polymeric materials. The focus is placed on the
      polymeric architecture, which is responsible for an efficient stress
      transmission, revealing the greatest activation for network-based
      mechanocatalysts, observing "click" conversions up to 44%, while chain-extended
      and linear mechanocatalysts activate either in a less efficient manner or are not
      completely latent in the initial state. The developed catalysts enable
      "irreversible" mechanochromic systems for stress-sensing devices.

PMID- 30101433
TI  - Predators.

PMID- 30101435
TI  - BAMM at the court of false equivalency: A response to Meyer and Wiens.
AB  - The software program BAMM has been widely used to study rates of speciation,
      extinction, and phenotypic evolution on phylogenetic trees. The program
      implements a model-based clustering algorithm to identify clades that share
      common macroevolutionary rate dynamics and to estimate parameters. A recent
      simulation study by Meyer and Wiens (M&W) argued that (1) a simple inference
      framework (MS) performs much better than BAMM, and (2) evolutionary rates
      inferred with BAMM are poorly correlated with true rates. I address two
      statistical concerns with their assessment that affect the generality of their
      conclusions. These considerations are not specific to BAMM and apply to other
      methods for estimating parameters from empirical data where the true grouping
      structure of the data is unknown. M&W constrain roughly half of the parameters in
      their MS analyses to their true values, but BAMM is given no such information and
      must estimate all parameters from the data. This information disparity results in
      a substantial degrees of freedom advantage for the MS estimators. When both
      methods are given equivalent information, BAMM outperforms the MS estimators.

PMID- 30101434
TI  - Detection of hypermethylated genes as markers for cervical screening in women
      living with HIV.
AB  - INTRODUCTION: To evaluate the performance of hypermethylation analysis of ASCL1,
      LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical
      cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with
      HIV (WLHIV) in South Africa. METHODS: Samples from a prospective observational
      cohort study were used for these analyses. Two cohorts were included: a cohort of
      WLHIV who were invited for cervical screening (n = 321) and a gynaecologic
      outpatient cohort of women referred for evaluation of abnormal cytology or biopsy
      proven cervical cancer (n = 108, 60% HIV seropositive). Cervical scrapes
      collected from all subjects were analysed for hypermethylation of ASCL1, LHX8 and
      ST6GALNAC5 by multiplex quantitative methylation specific PCR (qMSP). Histology
      endpoints were available for all study subjects. RESULTS: Hypermethylation levels
      of ASCL1, LHX8 and ST6GALNAC5 increased with severity of cervical disease. The
      performance for detection of CIN3 or worse (CIN3+ ) as assessed by the area under
      the receiver operating characteristic (ROC) curves (AUC) was good for ASCL1 and
      LHX8 (AUC 0.79 and 0.81 respectively), and moderate for ST6GALNAC5 (AUC 0.71). At
      a threshold corresponding to 75% specificity, CIN3+ sensitivity was 72.1% for
      ASCL1 and 73.8% for LHX8 and all samples from women with cervical cancer scored
      positive for these two markers. CONCLUSIONS: Hypermethylation analysis of ASCL1
      or LHX8 in cervical scrape material of WLHIV detects all cervical carcinomas with
      an acceptable sensitivity and good specificity for CIN3+ , warranting further
      exploration of these methylation markers as a stand-alone test for cervical
      screening in low-resource settings.

PMID- 30101436
TI  - Study on the levels of glycosylated lipoprotein in patients with coronary artery
      atherosclerosis.
AB  - BACKGROUND: The main risk factors for atherosclerosis patients are not fully
      explicated. The aim of this study was to analyze the levels of blood lipid and
      glycosylated lipoprotein in patients with coronary artery atherosclerosis and
      healthy individuals and to study the relationship between the glycosylated
      lipoprotein and atherosclerosis. METHODS: The study involved 200 patients
      diagnosed with myocardial infarction caused by coronary atherosclerosis as case
      group and 230 healthy individuals as control group. We analyzed and contrasted
      the levels of blood lipid and glycosylated lipoprotein between the different
      groups. In addition, we investigated the correlation between glycosylated low
      density lipoprotein (G-LDL) and glucose levels. RESULTS: There is no statistical
      difference between the level of TG in case group and control group. The level of
      CHOL, HDL-C, and LDL-C in case group is significantly lower than that in control
      group (3.90 [3.23, 4.42] vs 5.16 [4.86, 5.77] [mmol/L]; 1.09 [0.83, 1.38] vs 1.46
      [1.15, 1.80] [mmol/L]; 2.22 [1.68, 2.81] vs 2.95 [2.60, 3.27] [mmol/L]) (P <
      0.05). The level of GLU, HbA1c, G-HDL, and G-LDL in case group is significantly
      higher than that in control group (7.10 [5.68, 9.27] vs 4.84 [4.68, 5.07]
      [mmol/L]; 6.8 [6.3, 7.4] vs 5.9 [5.6, 6.1] [%]; 30.08 [25.04, 40.17] vs 22.95
      [18.14, 27.06] [ng/mL], 6.26 [4.95, 7.50] vs 3.61 [2.66, 5.15] [ng/mL]) (p <
      0.05). The level of G-LDL in patients with coronary atherosclerosis was relevant
      with the level of GLU and HbA1c (r = 0.625, 0.706, P < 0.05), and there was no
      relevance with LDL-C (r = 0.331, P > 0.05). CONCLUSION: Hyperlipidemia is not an
      important cause of coronary atherosclerosis. High glucose levels and glycosylated
      lipoprotein are of high importance in the development and progression of coronary
      atherosclerosis.

PMID- 30101437
TI  - Clinical relevance of serum antibodies to GD1b in immune-mediated neuropathies.
AB  - Antibodies to the ganglioside GD1b have been reported in various forms of immune
      mediated neuropathy, but their clinical relevance for diagnosis and prognosis is
      unknown. We investigated the prevalence of anti-GD1b antibodies in acute and
      chronic immune-mediated neuropathies, and the clinical presentation and outcome
      in Guillain-Barre syndrome (GBS) and Miller Fisher-GBS overlap syndrome (MF-GBS).
      Anti-GD1b, anti-GM1 and anti-GQ1b antibodies were tested in serum of patients
      with GBS (N = 165), Miller Fisher syndrome (N = 10), MF-GBS (N = 28), monoclonal
      gammopathy of unknown significance neuropathy (MGUS; N = 101), chronic
      inflammatory demyelinating polyneuropathy (N = 29), paraneoplastic syndrome with
      anti-Hu-associated neuropathy (PNS; N = 11), other auto-immune diseases (AID; N =
      60), and healthy controls (HC; N = 60). All samples were tested by enzyme-linked
      immunosorbent assay according to the Inflammatory Neuropathy Cause and Treatment
      protocol. IgM anti-GD1b antibodies were found in GBS (N = 4; 2.4%), MGUS (N = 3;
      3.0%), and PNS patients (N = 1; 9.1%). IgG anti-GD1b antibodies were found in GBS
      (N = 20; 12.1%) and MF-GBS (N = 4; 14.3%) patients, but not in the AID and HC
      group. In the combined group of MF-GBS and GBS patients ((MF-)GBS), 14/36 (38.9%)
      patients with IgG anti-GD1b antibodies also had IgG anti-GM1 antibodies, and IgG
      anti-GD1b and IgG anti-GQ1b antibodies were found in 3/29 (10.3%) patients.
      Patients with (MF-)GBS and anti-GD1b without anti-GM1 antibodies did not differ
      regarding sensory disturbances or disease severity but recovered faster regarding
      the ability to walk independently compared with patients without anti-GD1b
      antibodies (P = 0.031) and with patients with both anti-GD1b and anti-GM1
      antibodies (P = 0.034). In conclusion, testing for anti-GD1b antibodies may
      identify a specific group of immune-mediated neuropathies and (MF-)GBS patients
      with only anti-GD1b antibodies tend to recover faster.

PMID- 30101438
TI  - High-Capacity Upconversion Wavelength and Lifetime Binary Encoding for
      Multiplexed Biodetection.
AB  - Optical multiplexing plays an important role in fields ranging from advanced
      biological assays to security. However, conventional codes based on fluorescent
      color and intensity are limited to spectral overlap and background interference.
      Herein, we present a new multiplexing concept by manipulating the luminescence
      emission color and decay lifetimes of upconversion nanoparticles (taulambda 
      UCNPs) separately for the first time through designing the core/multi-shell
      structure and controlled energy relay method. This new color/lifetime binary
      strategy exhibits exponentially scalable encoding capacity (>105 ), three orders
      of magnitudes higher than that of conventional color/intensity way. The strategy
      enables the multiplexed detection of human papilloma virus (HPV) subtypes in
      patient samples and robust anti-counterfeiting. This work opens new opportunities
      for optical multiplexing with luminescent materials.

PMID- 30101440
TI  - Resident experiences with social media: modernizing dermatology training.

PMID- 30101439
TI  - FAME-04: A Phase 1 trial to assess the safety, acceptability, pharmacokinetics
      and pharmacodynamics of film and gel formulations of tenofovir.
AB  - INTRODUCTION: Fast-dissolving vaginal film formulations release antiretroviral
      drugs directly into vaginal fluid and may be as efficient at drug delivery yet
      more acceptable to women than gels. In this Phase 1 vaginal film study, the
      safety, acceptability, pharmacokinetics and pharmacodynamics of two doses of
      tenofovir (TFV) film and TFV 1% gel were compared to corresponding placebo
      formulations. METHODS: Seventy-eight healthy HIV negative women were randomized
      to self-insert daily vaginal film (10 mg TFV, 40 mg TFV or placebo) or 4 mL of
      vaginal gel (TFV 1% [40 mg] or placebo) for seven days. Grade 2 and higher
      adverse events (AEs) related to study product were compared across study arms
      using Fisher's exact test. Plasma TFV concentrations were measured before and 2
      hours after last product use. Paired cervical and vaginal tissue biopsies
      obtained 2 hours after the last dose were measured to determine tenofovir
      diphosphate (TFV-DP) concentrations and exposed to HIV in an ex vivo challenge
      assay. Acceptability was assessed through questionnaire. RESULTS: There was only
      one grade 2 or higher related AE, the primary endpoint; it occurred in the
      placebo gel arm. AEs occurred in 90% of participants; the majority (91%) were
      grade 1. AEs were similar across study arms. TFV concentrations in plasma and TFV
      DP concentrations in cervical and vaginal tissues were comparable between 40 mg
      TFV film and the TFV gel groups. There was a significant relationship between
      reduced viral replication and TFV-DP concentrations in cervical tissues. Film
      users were less likely to report product leakage than gel users (66% vs. 100%, p
      < 0.001). CONCLUSIONS: Films were safe and well tolerated. Furthermore, films
      delivered TFV to mucosal tissues at concentrations similar to gel and were
      sufficient to block HIV infection of genital tissue ex vivo.

PMID- 30101441
TI  - Contribution to the discussion of "When should meta-analysis avoid making hidden
      normality assumptions?"

PMID- 30101442
TI  - Pheno-Deep Counter: a unified and versatile deep learning architecture for leaf
      counting.
AB  - Direct observation of morphological plant traits is tedious and a bottleneck for
      high-throughput phenotyping. Hence, interest in image-based analysis is
      increasing, with the requirement for software that can reliably extract plant
      traits, such as leaf count, preferably across a variety of species and growth
      conditions. However, current leaf counting methods do not work across species or
      conditions and therefore may lack broad utility. In this paper, we present Pheno
      Deep Counter, a single deep network that can predict leaf count in two
      dimensional (2D) plant images of different species with a rosette-shaped
      appearance. We demonstrate that our architecture can count leaves from multi
      modal 2D images, such as visible light, fluorescence and near-infrared. Our
      network design is flexible, allowing for inputs to be added or removed to
      accommodate new modalities. Furthermore, our architecture can be used as is
      without requiring dataset-specific customization of the internal structure of the
      network, opening its use to new scenarios. Pheno-Deep Counter is able to produce
      accurate predictions in many plant species and, once trained, can count leaves in
      a few seconds. Through our universal and open source approach to deep counting we
      aim to broaden utilization of machine learning-based approaches to leaf counting.
      Our implementation can be downloaded at https://bitbucket.org/tuttoweb/pheno-deep
      counter.

PMID- 30101443
TI  - 2D Phosphorene: Epitaxial Growth and Interface Engineering for Electronic
      Devices.
AB  - Black phosphorus (BP), first synthesized in 1914 and rediscovered as a new member
      of the family of 2D materials in 2014, combines many extraordinary properties of
      graphene and transition-metal dichalcogenides, such as high charge-carrier
      mobility, and a tunable direct bandgap. In addition, it displays other
      distinguishing properties, e.g., ambipolar transport and highly anisotropic
      properties. The successful application of BP in electronic and optoelectronic
      devices has stimulated significant research interest in other allotropes and
      alloys of 2D phosphorene, a class of 2D materials consisting of elemental
      phosphorus. As an atomically thin sheet, the various interfaces presented in 2D
      phosphorene (substrate/phosphorene, electrode/phosphorene,
      dielectric/phosphorene, atmosphere/phosphorene) play dominant roles in its bottom
      up synthesis, and determine several key characteristics for the devices, such as
      carrier injection, carrier transport, carrier concentration, and device
      stability. The rational design/engineering of interfaces provides an effective
      way to manipulate the growth of 2D phosphorene, and modulate its electronic and
      optoelectronic properties to realize high-performance multifunctional devices.
      Here, recent progress of the interface engineering of 2D phosphorene is
      highlighted, including the epitaxial growth of single-layer blue phosphorus on
      different substrates, surface functionalization of BP for high-performance
      complementary devices, and the investigation of the BP degradation mechanism in
      ambient air.

PMID- 30101445
TI  - Effects of cortical anodal transcranial direct current stimulation on swallowing
      biomechanics.
AB  - BACKGROUND: Anodal transcranial direct current stimulation (tDCS) has
      demonstrated effects on corticobulbar excitability and swallowing function as
      assessed via clinical rating scales in stroke cohorts. Biomechanical effects of
      anodal tDCS on swallowing remain largely unexplored. We investigated how anodal
      tDCS applied over the floor of mouth (FOM) representation on the primary motor
      cortex affects swallowing biomechanics in healthy participants. METHODS: Anodal
      and sham tDCS were applied for 20 minutes at 1.5 mA. Corticobulbar excitability
      was assessed using motor evoked potentials at baseline and 0, 15, 30 and 45
      minutes post-tDCS, as assessed by transcranial magnetic stimulation. Swallowing
      function was assessed pre- and post-tDCS using routine clinical assessments
      (Study 1) and pharyngeal high resolution impedance manometry (Study 2). KEY
      RESULTS: Study 1 (n = 17) showed increased corticobulbar excitability and
      performance on a skilled swallowing task following anodal wetDCS, but not sham
      tDCS. In Study 2 (n = 10) anodal tDCS resulted in increased bolus admittance
      across the upper esophageal sphincter, but decreased pharyngeal and upper
      esophageal contractile vigor. CONCLUSIONS: Clinical improvements of dietary
      intake are likely driven by swallowing neuroplastic reorganization which improves
      bolus admittance across the upper esophageal sphincter (UES). INFERENCES: The
      documented changes make motor cortical application of anodal tDCS a promising
      adjunct to swallowing rehabilitation practice.

PMID- 30101444
TI  - Field monitoring of Helicoverpa armigera (Lepidoptera: Noctuidae) Cry1Ac
      insecticidal protein resistance in China (2005-2017).
AB  - BACKGROUND: Bt cotton expressing Cry1Ac can efficiently control Helicoverpa
      armigera, but field-evolved Bt resistance reduces its efficacy. Susceptibility of
      H. armigera field populations to Cry1Ac protein has been monitored since Bt
      cotton was commercialized in 1997 in China. Here we report the results of our
      continued monitoring from 2005 to 2017 to provide important guidelines for
      sustainably growing cotton. RESULTS: From 13 provinces and regions, 221
      populations were sampled and measured. IC50 values (concentration producing 50%
      inhibition of larval development to third instar) among different strains ranged
      from 0.004 to 0.212 ug mL-1 , the percentage survival at a diagnostic
      concentration (IC99 , 1.0 ug mL-1 ) (SUR) ranged from 0% to 22.2%, and the
      percentage of field populations yielding survivors at diagnostic concentration
      (PSD) increased from 0 in 2006 and 2007 to 80% in 2015. CONCLUSIONS: Compared to
      resistance level from 1998 to 2004 and the geographic baseline in different
      places of China in 1997, Bt resistance of H. armigera field populations to Cry1Ac
      protein has increased significantly, but failure of Bt cotton has not yet been
      detected. (c) 2018 Society of Chemical Industry.

PMID- 30101446
TI  - Presentation and disease course of childhood- versus adult-onset Takayasu
      Arteritis.
AB  - OBJECTIVE: To compare the clinical features, efficacy and safety of treatment
      regimens, and outcomes of childhood- and adult-onset Takayasu Arteritis (TAK).
      METHODS: This is a retrospective cohort study comparing patients with childhood
      onset TAK since 1986 and adult-onset TAK since 1988 followed at four centers in
      Ontario, Canada until 2015. Demographic, clinical, laboratory and angiographic
      features, treatment regimens and outcomes were recorded throughout the course of
      disease. Disease activity and damage scores were completed retrospectively.
      RESULTS: Twenty-nine children and 48 adults (median age at diagnosis 12.1 and
      31.2 years, respectively) were included. Children had lower female predominance
      (76% versus 100% in adults, p<0.01) and shorter diagnostic delay (median 6.0
      versus 12.2 months, p=0.03). The distribution of vascular involvement was also
      different with children having significantly more aortic and renal artery
      involvement with a higher frequency of arterial hypertension. Relapses in the
      first year after diagnosis were common in children (39%) and adults (28%); two
      children, but no adults died. CONCLUSION: Childhood-onset TAK has lower female
      predominance, higher frequency of aortic and renal involvement compared to adult
      TAK patients. Relapses and disease burden were high in both groups corroborating
      the need for careful monitoring of disease activity and aggressive therapeutic
      management. This article is protected by copyright. All rights reserved.

PMID- 30101447
TI  - Targeting NEDD8-activating enzyme is a new approach to treat canine diffuse large
      B-cell lymphoma.
AB  - Canine diffuse large B-cell lymphoma (DLBCL), the most common hematologic
      malignancy of dogs, is associated with poor overall survival. The lack of
      conventional chemotherapies with sustainable efficacy warrants investigation of
      novel therapies. Pevonedistat (MLN4924) is a potent and selective small molecule
      NEDD8-activating enzyme inhibitor. In human activated B-cell-like (ABC) diffuse
      large B-cell lymphoma, pevonedistat induces lymphoma cell apoptosis, DNA damage
      and G1 cell cycle arrest by inhibiting the nuclear factor-kappaB (NF-kappaB)
      pathway. Genomic and transcriptomic studies showed that the NF-kappaB pathway is
      deregulated in canine DLBCL. Our results showed that pevonedistat treatment
      significantly reduces the viability of canine DLBCL cells by inducing G1 cell
      cycle arrest and apoptosis. Pevonedistat treatment inhibits NF-kappaB pathway
      activation and downregulates NF-kappaB target genes in canine DLBCL. Moreover,
      administration of pevonedistat to mice bearing canine DLBCL xenograft tumours
      resulted in tumour regression. Our in vivo and in vitro studies provide
      justification for future clinical application of pevonedistat as a potential new
      anti-cancer therapy that may benefit both canine and human species.

PMID- 30101449
TI  - Deleterious mutations of MC1R in guinea pig.

PMID- 30101448
TI  - Investigation of facilitative urea transporters in the human gastrointestinal
      tract.
AB  - The symbiotic relationship between humans and their intestinal microbiome is
      supported by urea nitrogen salvaging. Previous studies have shown that colonic UT
      B urea transporters play a significant role in this important physiological
      process. This current study investigated UT-A and UT-B urea transporter
      expression along the human gastrointestinal tract. Initial end-point PCR
      experiments determined that UT-A RNA was predominantly expressed in the small
      intestine, while UT-B RNA was expressed in stomach, small intestine, and colon.
      Using western blotting experiments, a strong 40-60 kDa UT-B signal was found to
      be abundant in both ileum and colon. Importantly, this signal was deglycosylated
      by PNGaseF enzyme treatment to a core protein of 30 kDa in both tissues. Further
      immunolocalization studies revealed UT-B transporter proteins were present at the
      apical membrane of the villi in the ileum, but predominantly at the basolateral
      membrane of the colonic surface epithelial cells. Finally, a blind scoring
      immunolocalization study suggested that there was no significant difference in UT
      B abundance throughout the colon (NS, ANOVA, N = 5-21). In conclusion, this
      current study suggested UT-B to be the main human intestinal urea transporter.
      Intriguingly, these data suggested that the same UT-B isoform was present in all
      intestinal epithelial cells, but that the precise cellular location varied.

PMID- 30101450
TI  - The changes of antifungal susceptibilities caused by the phenotypic switching of
      Candida species in 229 patients with vulvovaginal candidiasis.
AB  - OBJECTIVE: This study was to investigate the changes of antifungal
      susceptibilities caused by the phenotypic switching in patients with vulvovaginal
      candidiasis (VVC). METHODS: 229 women were enrolled in this study. The vaginal
      smears of these patients were collected and gram stained for fungal microscopic
      observation. The vaginal discharge of them in cotton swabs was cultured in
      sabouraud's agar with chloramphenicol medium. After fungal culture, fungal
      identification was analyzed using CHROM agar Candida chromogenic and
      identification medium. Then, the in vitro antifungal susceptibility testing was
      carried out using the standardized CLSI M27-A2 broth microdilution method.
      RESULTS: 64.63% of Candia species in patients with VVC were Candida albicans and
      the remainders were non-albicans Candida species. The phenotypic switching was
      observed in 91.22% of C. albicans infection. In antifungal susceptibility
      testing, the susceptible rates of C. albicans to voriconazole, fluconazole and
      itraconazole were significantly higher than that of non-albicans Candida species
      (P = 0.00, 0.00, 0.00). No matters in patients infected with C. albicans or with
      non-albicans Candida species, the susceptible rate to fluconazole of the clinical
      isolates with phenotypic switching was significantly higher than that without
      phenotypic switching (P = 0.01, 0.01). CONCLUSIONS: In the study, C. albicans was
      the commonest pathogenic species in patients with VVC, in which the phenotypic
      switching was easy to occur. The susceptible rates of C. albicans to all
      antifungal drugs were higher than that of non-albicans Candida species. The
      susceptible rate to fluconazole was all influenced by the phenotypic switching in
      C. albicans and non-albicans Candida species.

PMID- 30101451
TI  - Contrasting Synergistic Heterobimetallic (Na-Mg) and Homometallic (Na or Mg)
      Bases in Metallation Reactions of Dialkylphenylphosphines and Dialkylanilines:
      Lateral versus Ring Selectivities.
AB  - A series of dialkylphenylphosphines and their analogous aniline substrates have
      been metallated with the synergistic mixed-metal base [(TMEDA)Na(TMP)(CH2 SiMe3
      )Mg(TMP)] 1. Different metallation regioselectivities for the substrates were
      observed, with predominately lateral or meta-magnesiated products isolated from
      solution. Three novel heterobimetallic complexes [(TMEDA)Na(TMP)(CH2 PCH3
      Ph)Mg(TMP)] 2, [(TMEDA)Na(TMP)(m-C6 H4 PiPr2 )Mg(TMP)] 3 and [(TMEDA)Na(TMP)(m-C6
      H4 NEt2 )Mg(TMP)]  4 and two homometallic complexes [{(TMEDA)Na(EtNC6 H5 )}2 ] 5
      and [(TMEDA)Na2 (TMP)(C6 H5 PEt)]2  6 derived from homometallic metallation have
      been crystallographically characterised. Complex 6 is an unprecedented sodium
      amide, sodium-phosphide hybrid with a rare (NaNNaP)2 ladder motif. These products
      reveal contrasting heterobimetallic deprotonation with homometallic induced
      ethene elimination reactivity. Solution studies of metallation mixtures and
      electrophilic iodine quenching reactions confirmed the metallation sites. In an
      attempt to rationalise the regioselectivity of the magnesiation reactions the C-H
      acidities of the six substrates were determined in THF solution using DFT
      calculations employing the M06-2X functional and cc-pVTZ Dunning's basis set.

PMID- 30101452
TI  - Twenty-four-hour ambulatory ECG monitoring relevancy in myotonic dystrophy type 1
      follow-up: Prognostic value and heart rate variability evolution.
AB  - BACKGROUND: Patient prognosis in type 1 myotonic dystrophy (DM1) is very poor.
      Annual 24-hour holter ECG monitoring is recommended but its relevance is debated.
      Main objective was to determine whether holter ECG parameters could predict
      global death in DM1 patients and secondarily to assess whether they could predict
      cardiovascular events and sudden cardiac death, to compare DM1 patients and
      healthy controls, and to assess their evolution in DM1 over a 5-year period.
      METHODS: This retrospective study included genetically confirmed DM1. Primary
      endpoint was global death. Secondary endpoints were labeled "sudden cardiac
      death" which was a composite of sudden cardiac death, aborted sudden cardiac
      death, implantable cardioverter defibrillator therapy, sustained ventricular
      tachycardia, atrioventricular block grade 3, pause >3 s; and "cardiovascular
      events" which was a composite of all-cause mortality, pacemaker or cardioverter
      defibrillator implantation, sustained ventricular tachycardia, supraventricular
      tachycardia, hospitalization for acute cardiac cause and heart failure. RESULTS:
      Forty-seven patients (22 women, 40 +/- 13 years old) were included. Three (7%)
      DM1 patients died, 9 (19%) experienced "sudden cardiac death" endpoint and 21
      (45%) experienced "cardiovascular event" endpoint during mean follow-up of 95 +/-
      22 months. None of holter ECG parameters were discriminant to predict death or
      secondary endpoints. Compared to healthy controls, DM1 patients had higher SDNN
      and LF/HF ratio. Finally, heart rate variability parameters remained stable over
      a mean interval of 61 +/- 15 months excepting pNN50 which decreased
      significantly. CONCLUSION: Results suggest that annually-repeated holter ECG in
      DM1 is not useful for stratifying risk of sudden death and cardiovascular
      outcomes.

PMID- 30101453
TI  - Modular Redesign of a Cationic Lytic Peptide To Promote the Endosomal Escape of
      Biomacromolecules.
AB  - Endocytosis is an important route for the intracellular delivery of
      biomacromolecules, wherein their inefficient endosomal escape into the cytosol
      remains a major barrier. Based on the understanding that endosomal membranes are
      negatively charged, we focused on the potential of cationic lytic peptides for
      developing endosomolysis agents to release such entrapped molecules. As such, a
      venom peptide, Mastoparan X, was employed and redesigned to serve as a delivery
      tool. Appending a tri-glutamate unit to the N-terminus attenuates the
      cytotoxicity of Mastoparan X by about 40 fold, while introduction of a NiII 
      dipicolylamine complex enhances cellular uptake of the peptide by about 17 fold.
      Using the optimized peptide, various fluorescently labeled macromolecules were
      successfully delivered to the cytosol, enabling live-cell imaging of acetylated
      histones.

PMID- 30101455
TI  - Measuring patient-centredness in publicly funded fertility care: A New Zealand
      validation and international comparison of the Patient-Centred Questionnaire
      Infertility.
AB  - BACKGROUND: The Patient-Centred Questionnaire-Infertility (PCQ-Infertility) has
      proven to be a reliable instrument to assess the extent of patient-centredness of
      fertility care in European countries. AIMS: To validate the PCQ-Infertility in
      New Zealand (NZ) and to compare results with international experience. MATERIALS
      AND METHODS: A cross-sectional 46-item questionnaire study among 409 women
      undergoing publicly funded fertility care (intrauterine insemination or in vitro
      fertilisation / intracytoplasmic sperm injection) in three fertility clinics in
      the Northern Auckland region was performed between October 2015 and September
      2016. Inclusion of eligible participants was both retro- and prospective. The
      questionnaire was distributed by email link and women were asked to complete it
      with their partner. Internal consistency and construct validity were determined
      and correction for case mix was performed. Mean dimension scores, adjusted for
      'current pregnancy', 'educational level' and 'treatment type', were calculated
      for each dimension of the PCQ-Infertility. NZ results were compared with PCQ
      Infertility results from five countries. RESULTS: Of 409 invited women, 255
      questionnaires were submitted (response rate 62%), of which 216 (53%) were
      analysable. The dimension 'Care organization' had poor internal consistency, but
      overall the questionnaire had high internal consistency (Cronbach's alpha =
      0.93). Construct validity was also good. International comparison showed NZ to
      have the second highest overall score. In New Zealand, the lowest scoring domain
      was 'Continuity and transition'. CONCLUSIONS: The NZ version of the PCQ
      infertility proved a valid instrument for the assessment of patient-centredness
      of publicly funded fertility care. Future research should focus on international
      inequities in patient-centred fertility care and use of the tool for quality
      improvement. Local use of the PCQ-Infertility is encouraged.

PMID- 30101454
TI  - Risk-based management strategy and outcomes of tumor lysis syndrome in children
      with leukemia/lymphoma: Analysis from a resource-limited setting.
AB  - BACKGROUND: Data from low- and middle-income countries on tumor lysis syndrome
      (TLS) in the pediatric population are limited. This study aims to analyze the
      clinical and biochemical characteristics and treatment outcomes of TLS in
      children with leukemia/lymphomas in a resource-limited setting. PROCEDURE:
      Children with intermediate risk (IRD) and high risk (HRD) for developing TLS were
      retrospectively studied at a tertiary cancer center in India. RESULTS: Over a
      three-year period, 224 children with acute leukemia/lymphoma having IRD (21.8%, n
      = 49) and HRD (78.1%, n = 175) were identified. TLS developed in 53.6% (n = 120)
      cases, of which 75% (n = 90) had laboratory TLS alone. Thirteen children had
      clinical TLS (C-TLS) at presentation while 17 patients progressed to develop C
      TLS. TLS developed in 51% (n = 25) and 54.5% (n = 95) of children with IRD and
      HRD, respectively. Rasburicase was used in 8.5% (n = 19) cases and five children
      required hemodialysis. Two children (0.8%) expired during the course of TLS
      management. Multivariate analysis identified the presence of hyperuricemia as the
      single significant risk factor for developing TLS. When children in whom a 25%
      change in biochemical values from the baseline that falls within the normal range
      were excluded, 21.4% (48/224) cases were identified to have clinically relevant
      TLS (8% in IRD and 25% in HRD). CONCLUSION: With hydration, supportive care and
      judicious use of rasburicase, it is feasible to manage TLS efficiently in
      resource-limited settings. A modification of the TLS definition criteria would
      help to identify clinically relevant TLS.

PMID- 30101456
TI  - Digest: How mutational bias could explain the maintenance of sex.
AB  - How does mutational bias affect the fitness of populations under different
      reproductive strategies? Vanhoenacker et al. (2018) found that mutational bias
      can greatly reduce the mean fitness of asexual populations, offering a new
      hypothesis for the maintenance of sex.

PMID- 30101457
TI  - Effects of lily/maize intercropping on rhizosphere microbial community and yield
      of Lilium davidii var. unicolor.
AB  - Continuous cropping of lily (Lilium davidii var. unicolor) or any other crop
      seriously affects yield and quality. In this study, we compared continuous
      cropping with lily/maize intercropping. We also examined the lily rhizosphere
      microbes community in both sole lily cropping and lily/maize intercropping
      systems, by the llumina Miseq platform. Here we refer to data of recent years
      field experimentation of a lily/maize intercrop system in different planting
      configurations in the Gaolan Ecological and Agricultural Research Station.
      Treatments included sole crops of lily and maize, an intercrop consisting of
      strips of four lily rows alternating with one maize rows. The land equivalent
      ratio (LER) of intercrops was 1.294. The results showed that compared to sole
      cropping, the yield of lily in the first year of planting increased when lily was
      intercropped with maize. The species annotation of the high-throughput sequencing
      experiment showed that there was no difference in the diversity of the lily
      rhizosphere soil microbes on phylum taxonomic level, but the relative abundance
      of some genus changed obviously. The relative abundance of harmful fungus
      Fusarium spp. and, Funneliformis spp., decreased, and the relative abundance of
      beneficial bacteria Sphingomonas spp. and, Nitrospira spp., increased. In
      addition, we found that Lecanicillium spp., appeared only in the intercropping
      lily rhizosphere soil and sole cropping maize rhizosphere soil. In conclusion,
      the findings indicated that lily/maize intercropping could change soil
      microenvironment, and affect the diversity and structure of microorganism
      community in lily rhizosphere, with further beneficial effect on the yield of
      lily.

PMID- 30101458
TI  - A comparative study of subsequent liver cirrhosis risk in non-Helicobacter pylori
      infected peptic ulcer patients with and without vagotomy: An Asian population
      cohort study.
AB  - OBJECTIVES: Hepatic parasympathetic nerves branch off the vagus nerve. The vagal
      and hepatic nervous systems are important in liver physiological processes and
      some diseases such as diabetes, obesity, and liver cirrhosis. We were interested
      in vagal nerve integrity and subsequent diseases in peptic ulcer patients.
      Herein, we used National Health Insurance database in Taiwan and retrospectively
      assessed the risk of developing liver cirrhosis in peptic ulcer patients with and
      without complications by surgical treatments. METHODS: A cohort of 357 423 peptic
      ulcer patients without Helicobacter pylori, hepatitis B/C virus infection, and
      alcoholism from 2001 to 2008 was established. A randomly selected cohort of 357
      423 people without peptic ulcer that matched by age, gender, comorbidities, and
      index year was used for comparison. The risks of developing liver cirrhosis were
      assessed both in cohorts and in peptic ulcer patients with and without vagotomy
      at the end of 2011. RESULTS: Peptic ulcer patients were with higher incidence of
      liver cirrhosis than those without peptic ulcer (2.63 vs 0.96 per 1000 person
      years) and with a 2.79-fold adjusted hazard ratio (HR) (95% confidence interval =
      2.66-2.93) based on the multivariable Cox proportional hazards regression
      analysis. Comparing with different peptic ulcer management strategies, the HR
      value for subsequent liver cirrhosis risk was the lowest in vagotomy group (HR =
      0.46, 95% confidence interval = 0.33-0.64). CONCLUSIONS: Peptic ulcer patients
      have an increased risk of developing liver cirrhosis. Moreover, there were
      association of vagotomy and decreased risk of subsequent liver cirrhosis in
      complicated peptic ulcer patients. However, further studies are warranted.

PMID- 30101459
TI  - Why a randomized melanoma screening trial may be a good idea.

PMID- 30101460
TI  - Genetic regulatory pathways of split-hand/foot malformation.
AB  - Split-hand/foot malformation (SHFM) is caused by mutations in TP63, DLX5, DLX6,
      FGF8, FGFR1, WNT10B, and BHLHA9. The clinical features of SHFM caused by
      mutations of these genes are not distinguishable. This implies that in normal
      situations these SHFM-associated genes share an underlying regulatory pathway
      that is involved in the development of the central parts of the hands and feet.
      The mutations in SHFM-related genes lead to dysregulation of Fgf8 in the central
      portion of the apical ectodermal ridge (AER) and subsequently lead to
      misexpression of a number of downstream target genes, failure of stratification
      of the AER, and thus SHFM. Syndactyly of the remaining digits is most likely the
      effects of dysregulation of Fgf-Bmp-Msx signaling on apoptotic cell death. Loss
      of digit identity in SHFM is hypothesized to be the effects of misexpression of
      HOX genes, abnormal SHH gradient, or the loss of balance between GLI3A and GLI3R.
      Disruption of canonical and non-canonical Wnt signaling is involved in the
      pathogenesis of SHFM. Whatever the causative genes of SHFM are, the mutations
      seem to lead to dysregulation of Fgf8 in AER cells of the central parts of the
      hands and feet and disruption of Wnt-Bmp-Fgf signaling pathways in AER.

PMID- 30101461
TI  - Rational Design of Supramolecular Dynamic Protein Assemblies by Using a Micelle
      Assisted Activity-Based Protein-Labeling Technology.
AB  - The self-assembly of proteins into higher-order superstructures is ubiquitous in
      biological systems. Genetic methods comprising both computational and rational
      design strategies are emerging as powerful methods for the design of synthetic
      protein complexes with high accuracy and fidelity. Although useful, most of the
      reported protein complexes lack a dynamic behavior, which may limit their
      potential applications. On the contrary, protein engineering by using chemical
      strategies offers excellent possibilities for the design of protein complexes
      with stimuli-responsive functions and adaptive behavior. However, designs based
      on chemical strategies are not accurate and therefore, yield polydisperse samples
      that are difficult to characterize. Here, we describe simple design principles
      for the construction of protein complexes through a supramolecular chemical
      strategy. A micelle-assisted activity-based protein-labeling technology has been
      developed to synthesize libraries of facially amphiphilic synthetic proteins,
      which self-assemble to form protein complexes through hydrophobic interaction.
      The proposed methodology is amenable for the synthesis of protein complex
      libraries with molecular weights and dimensions comparable to naturally occurring
      protein cages. The designed protein complexes display a rich structural
      diversity, oligomeric states, sizes, and surface charges that can be engineered
      through the macromolecular design. The broad utility of this method is
      demonstrated by the design of most sophisticated stimuli-responsive systems that
      can be programmed to assemble/disassemble in a reversible/irreversible fashion by
      using the pH or light as trigger.

PMID- 30101462
TI  - Krupple-like factor 5 is essential for mammary gland development and
      tumorigenesis.
AB  - Krupple-like factor 5 (KLF5) is required for the development of the embryo and
      multiple organs, such as the lung and intestine. KLF5 plays a pro-proliferative
      and oncogenic role in several carcinomas, including breast cancer. However, its
      role in normal mammary gland development and oncogenesis has not been elucidated
      in vivo. In this study, we used mammary gland-specific Klf5 conditional knockout
      mice derived by mating Klf5-LoxP and MMTV-Cre mice. The genetic ablation of Klf5
      suppresses mammary gland ductal elongation and lobuloalveolar formation. Klf5
      deficiency inhibits mammary epithelial cell proliferation, survival, and stem
      cell maintenance. Klf5 promotes mammary stemness, at least partially, by directly
      promoting the transcription of Slug. Finally, Klf5 depletion suppressed PyMT
      induced mammary gland tumor cell stemness, tumor initiation, and growth in vivo.
      Slug also mediated these functions of Klf5 in vivo. Copyright (c) 2018
      Pathological Society of Great Britain and Ireland. Published by John Wiley &
      Sons, Ltd.

PMID- 30101463
TI  - A tomato B-box protein SlBBX20 modulates carotenoid biosynthesis by directly
      activating PHYTOENE SYNTHASE 1, and is targeted for 26S proteasome-mediated
      degradation.
AB  - Carotenoids play important roles in many biological processes, such as light
      harvesting, photoprotection and visual attraction in plants. However, the
      regulation of carotenoid biosynthesis is still not fully understood. Here, we
      demonstrate that SlBBX20, a B-box (BBX) zinc-finger transcription factor, is a
      positive regulator of carotenoid accumulation in tomato (Solanum lycopersicum).
      Overexpression of SlBBX20 leads to dark green fruits and leaves and higher levels
      of carotenoids relative to the wild-type. Interactions between SlBBX20 and DE
      ETIOLATED 1 (SlDET1) lead to the ubiquitination and 26S proteasome-mediated
      degradation of SlBBX20. Moreover, deficiencies in the components of the CUL4-DDB1
      DET1 complex enhanced the stability of the SlBBX20 protein. Thus, we conclude
      that SlBBX20 is a substrate of the CUL4-DDB1-DET1 E3 ligase. SlBBX20 can activate
      the expression of PHYTOENE SYNTHASE 1, encoding a key enzyme in carotenoid
      biosynthesis, by directly binding to a G-box motif in its promoter, which results
      in the elevated levels of carotenoids in SlBBX20 overexpression lines. We
      identified a key regulator of carotenoid biosynthesis and demonstrated that the
      stability of SlBBX20 is regulated by ubiquitination. These findings provide us a
      new target for the genetic improvement of the nutritional quality of tomato
      fruit.

PMID- 30101465
TI  - Cottrell Scholars: L. K. Charkoudian, G. M. Miyake, C. Risko, A. M. Spokyny /
      TREE Awards: M. Gruebele, T. W. Odom, and G. C. Shields / Humboldt and Bessel
      Research Awards.

PMID- 30101466
TI  - Contribution to the discussion of "When should meta-analysis avoid making hidden
      normality assumptions?"

PMID- 30101468
TI  - What the neighbors say.

PMID- 30101467
TI  - Muscle-Inspired Highly Anisotropic, Strong, Ion-Conductive Hydrogels.
AB  - Biological tissues generally exhibit excellent anisotropic mechanical properties
      owing to their well-developed microstructures. Inspired by the aligned structure
      in muscles, a highly anisotropic, strong, and conductive wood hydrogel is
      developed by fully utilizing the high-tensile strength of natural wood, and the
      flexibility and high-water content of hydrogels. The wood hydrogel exhibits a
      high-tensile strength of 36 MPa along the longitudinal direction due to the
      strong bonding and cross-linking between the aligned cellulose nanofibers (CNFs)
      in wood and the polyacrylamide (PAM) polymer. The wood hydrogel is 5 times and
      500 times stronger than the bacterial cellulose hydrogels (7.2 MPa) and the
      unmodified PAM hydrogel (0.072 MPa), respectively, representing one of the
      strongest hydrogels ever reported. Due to the negatively charged aligned CNF, the
      wood hydrogel is also an excellent nanofluidic conduit with an ionic conductivity
      of up to 5 * 10-4 S cm-1 at low concentrations for highly selective ion
      transport, akin to biological muscle tissue. The work offers a promising strategy
      to fabricate a wide variety of strong, anisotropic, flexible, and ionically
      conductive wood-based hydrogels for potential biomaterials and nanofluidic
      applications.

PMID- 30101469
TI  - Soft Electronically Functional Polymeric Composite Materials for a Flexible and
      Stretchable Digital Future.
AB  - Flexible/stretchable electronic devices and systems are attracting great
      attention because they can have important applications in many areas, such as
      artificial intelligent (AI) robotics, brain-machine interfaces, medical devices,
      structural and environmental monitoring, and healthcare. In addition to the
      electronic performance, the electronic devices and systems should be mechanically
      flexible or even stretchable. Traditional electronic materials including metals
      and semiconductors usually have poor mechanical flexibility and very limited
      elasticity. Three main strategies are adopted for the development of
      flexible/stretchable electronic materials. One is to use organic or polymeric
      materials. These materials are flexible, and their elasticity can be improved
      through chemical modification or composition formation with plasticizers or
      elastomers. Another strategy is to exploit nanometer-scale materials. Many
      inorganic materials in nanometer sizes can have high flexibility. They can be
      stretchable through the composition formation with elastomers. Ionogels can be
      considered as the third type of materials because they can be stretchable and
      ionically conductive. This article provides the recent progress of soft
      functional materials development including intrinsically conductive polymers for
      flexible/stretchable electrodes, and thermoelectric conversion and polymer
      composites for large area, flexible stretchable electrodes, and tactile sensors.

PMID- 30101470
TI  - Chronic nausea and orthostatic intolerance: Diagnostic utility of orthostatic
      challenge duration, Nausea Profile Questionnaire, and neurohumoral measures.
AB  - BACKGROUND: Chronic nausea in pediatrics is a debilitating condition with unclear
      etiology. We aimed to define hemodynamic and neurohumoral characteristics of
      chronic nausea associated with orthostatic intolerance in order to improve
      identification and elucidate mechanism. METHODS: Children (10-18 years) meeting
      Rome III criteria for functional dyspepsia with nausea and symptoms of
      orthostatic intolerance (OI) completed a Nausea Profile Questionnaire followed by
      prolonged (45 minutes rather than the traditional 10 minutes) head-upright tilt
      (HUT) (70 degrees  tilt up) test. Circulating catecholamines, vasopressin,
      aldosterone, renin, and angiotensins were measured supine and after 15 minutes
      into HUT. Beat-to-beat heart rate and blood pressure were continuously recorded
      to calculate their variability and baroreflex sensitivity. KEY RESULTS: Within 10
      and 45 minutes of HUT, 46% and 85% of subjects, respectively, had an abnormal
      tilt test (orthostatic hypotension, postural orthostatic tachycardia, or
      syncope). At 15 and 45 minutes of HUT, nausea was elicited in 42% and 65% of
      subjects respectively. Higher Nausea Profile Questionnaire scores correlated with
      positive HUT testing at 10 minutes (P = 0.004) and baroreflex sensitivity at 15
      minutes (P <= 0.01). Plasma vasopressin rose 33-fold in subjects with HUT-induced
      nausea compared to twofold in those who did not experience HUT-induced nausea (P
      < 0.01). CONCLUSIONS AND INFERENCES: In children with chronic nausea and OI,
      longer duration HUT elicited higher frequency of abnormal tilt testing and
      orthostatic-induced nausea. The Nausea Profile Questionnaire predicted the
      orthostatic response to tilt testing. Exaggerated vasopressin release
      differentiated patients with HUT-induced nausea (vs those without nausea),
      suggesting a possible mechanism for chronic nausea in childhood.

PMID- 30101464
TI  - Human beta-defensin-1: A natural antimicrobial peptide present in amniotic fluid
      that is increased in spontaneous preterm labor with intra-amniotic infection.
AB  - PROBLEM: Human beta-defensins (HBDs) are antimicrobial peptides that participate
      in the soluble innate immune mechanisms against infection. Herein, we determined
      whether HBD-1 was present in amniotic fluid during normal pregnancy and whether
      its concentrations change with intra-amniotic inflammation and/or infection.
      METHOD OF STUDY: Amniotic fluid was collected from 219 women in the following
      groups: (a) midtrimester who delivered at term (n = 35); (b) term with (n = 33)
      or without (n = 17) labor; (c) preterm labor with intact membranes who delivered
      at term (n = 29) or who delivered preterm with (n = 19) and without (n = 29)
      intra-amniotic inflammation and infection or with intra-amniotic inflammation but
      without infection (n = 21); and (d) preterm prelabor rupture of membranes (pPROM)
      with (n = 19) and without (n = 17) intra-amniotic inflammation/infection.
      Amniotic fluid HBD-1 concentrations were determined using a sensitive and
      specific ELISA kit. RESULTS: (a) HBD-1 was detectable in all amniotic fluid
      samples; (b) amniotic fluid concentrations of HBD-1 were changed with gestational
      age (midtrimester vs term no labor), being higher in midtrimester; (c) amniotic
      fluid concentrations of HBD-1 were similar between women with and without
      spontaneous labor at term; (d) among patients with spontaneous preterm labor,
      amniotic fluid concentrations of HBD-1 in women with intra-amniotic
      inflammation/infection and in those with intra-amniotic inflammation without
      infection were greater than in women without intra-amniotic inflammation or
      infection who delivered preterm or at term; and (e) the presence of intra
      amniotic inflammation and infection in patients with pPROM did not change
      amniotic fluid concentrations of HBD-1. CONCLUSION: HBD-1 is a physiological
      constituent of amniotic fluid that is increased in midtrimester during normal
      pregnancy and in the presence of culturable microorganisms in the amniotic
      cavity. These findings provide insight into the soluble host defense mechanisms
      against intra-amniotic infection.

PMID- 30101471
TI  - Constitutive overexpression of cytochrome P450 monooxygenase genes contributes to
      chlorantraniliprole resistance in Chilo suppressalis (Walker).
AB  - BACKGROUND: The rice striped stem borer (SSB), Chilo suppressalis (Walker), which
      is one of the most economically important phytophagous pests, has developed
      resistance to multiple insecticides. The resistance of SSB against
      chlorantraniliprole has been investigated in detail. However, the mechanism of
      its metabolic resistance has rarely been studied. RESULTS: A field population
      from Wuhu City, China was used to establish chlorantraniliprole resistant and
      susceptible strains (WHR and WHS) by laboratory continuous selection. Enzyme
      activities data suggested the potential involvement of cytochrome P450
      monooxygenase in WHR. CYP6CV5, CYP9A68, CYP321F3, and CYP324A12 were
      significantly overexpressed in WHR (from 4.48 to 44.88-fold). These four P450
      genes were expressed in the late developmental stages of WHR; however, they were
      almost absent during the egg stage. In addition, their expressions were much more
      sensitive to chlorantraniliprole induction in WHR than in WHS. Injection of
      individual and mixture dsRNAs reduced the expression of the four target genes
      (55.2-73.2% and 43.2-50.2%, respectively) and caused significant larvae mortality
      (55.1-65.1% and 88.2%, respectively). CONCLUSION: Multiple overexpressed P450
      genes were potentially associated with chlorantraniliprole resistance, as
      confirmed by the RNA interference (RNAi) assay. Our findings suggested that
      metabolic resistance to chlorantraniliprole might be mediated by P450s. (c) 2018
      Society of Chemical Industry.

PMID- 30101472
TI  - FibroSURE and elastography poorly predict the severity of liver fibrosis in
      Fontan-associated liver disease.
AB  - OBJECTIVE: As the population of patients with Fontan circulation surviving into
      adulthood increases, hepatic cirrhosis has grown to be a significant cause of
      morbidity and mortality. Early detection of advanced hepatic fibrosis is
      imperative for proper intervention and consideration for heart or combined
      heart/liver transplantation. Noninvasive biomarkers and elastography have been
      evaluated for their diagnostic utility with variable results in the Fontan
      population. DESIGN: The cohort included 14 patients age 26.4 SD 7.5 who underwent
      Fontan surgery. All patients were evaluated with FibroSURE, shear wave
      elastography (SWE), hepatic duplex sonography, and liver biopsy. Liver fibrosis
      on biopsy was evaluated according to the congestive hepatic fibrosis system.
      RESULTS: In our cohort, 100% of patients had fibrosis with 36% demonstrating
      advanced fibrosis. FibroSURE agreed with liver biopsy in only 5 out of 14 cases
      (36%): underestimating in 7 and overestimating in 2 individuals. SWE agreed with
      liver biopsy in 0% of cases: overestimating in 10 and underestimating in 4 cases.
      None of the duplex sonography indices predicted the presence or severity of liver
      fibrosis. CONCLUSION: This study demonstrates that children who have undergone a
      Fontan procedure universally develop some hepatic fibrosis and a significant
      number have advanced fibrosis by adulthood. The FibroSURE blood test, SWE, and
      hepatic duplex sonography were unable to accurately predict the presence or
      severity of hepatic fibrosis when compared with liver biopsy. Further studies are
      needed to investigate novel noninvasive methods and/or biomarkers that can
      adequately detect advanced hepatic fibrosis before the development of cirrhosis
      and hepatic decompensation.

PMID- 30101474
TI  - Altered gray matter volumes in language-associated regions in children with
      developmental language disorder and speech sound disorder.
AB  - Developmental language disorder (DLD) and speech sound disorder (SSD) are common,
      and although scientific evidence for structural and functional alterations in
      DLD/SSD is accumulating, current neuroimaging studies provide an incongruent
      picture. Here, we hypothesized that children affected by DLD and SSD present with
      gray matter (or gray matter asymmetry) aberrations in brain areas associated with
      language processing compared to typically developing (TD) children. To assess
      this hypothesis, we enhanced MRI-based information with microscopically defined
      cytoarchitectonic probabilities of Broca's area (BA 45, BA 44) as well as an
      auditory area (TE 3.0). We detected a larger rightward gray matter asymmetry in
      BA 45 in children with DLD (n = 13) and with SSD (n = 18) compared to TD children
      (n = 18), albeit only on a trend level. Interestingly though, we observed
      significantly larger gray matter volumes in right BA 45 in DLD compared to SSD
      children (and also compared to TD children).

PMID- 30101475
TI  - Tritiation of azido-labeled diiodo cabazitaxel (Jevtana) and docetaxel (Taxotere)
      derivatives to generate 3 H-photoaffinity probes.
AB  - Radiolabelled azidophenyl analogues can make powerful photoaffinity probes for
      the identification of molecular targets. We describe our efforts to prepare
      tritiated azidophenyl analogues of the taxols cabazitaxel and docetaxel. Late
      stage tritiation by isotope exchange with diiodo precursors resulted in reduction
      of the azide moiety, which could only be overcome by addition of high excess of a
      sacrificial azide. Iodine-deuterium exchange experiments on a model system
      established that deiodination with concomitant azide reduction is a general
      problem when performing such isotope-exchange reactions on azide-containing aryl
      iodides.

PMID- 30101476
TI  - Hybridization-facilitated genome merger and repeated chromosome fusion after 8
      million years.
AB  - The small genus Ricotia (nine species, Brassicaceae) is confined to the eastern
      Mediterranean. By comparative chromosome painting and a dated multi-gene
      chloroplast phylogeny, we reconstructed the origin and subsequent evolution of
      Ricotia. The ancestral Ricotia genome originated through hybridization between
      two older genomes with n = 7 and n = 8 chromosomes, respectively, on the Turkish
      mainland during the Early Miocene (c. 17.8 million years ago, Ma). Since then,
      the allotetraploid (n = 15) genome has been altered by two independent descending
      dysploidies (DD) to n = 14 in Ricotia aucheri and the Tenuifolia clade (2 spp.).
      By the Late Miocene (c. 10 Ma), the latter clade started to evolve in the most
      diverse Ricotia core clade (6 spp.), the process preceded by a DD event to n =
      13. It is noteworthy that this dysploidy was mediated by a unique chromosomal
      rearrangement, merging together the same two chromosomes as were merged during
      the origin of a fusion chromosome within the paternal n = 7 genome c. 20 Ma. This
      shows that within a time period of c. 8 Myr genome evolution can repeat itself
      and that structurally very similar chromosomes may originate repeatedly from the
      same ancestral chromosomes by different pathways (end-to-end translocation versus
      nested chromosome insertion).

PMID- 30101477
TI  - Protein kinase D1 and oxysterol-binding protein form a regulatory complex
      independent of phosphorylation.
AB  - Protein kinase D (PKD) controls secretion from the trans-Golgi network (TGN) by
      phosphorylating phosphatidylinositol 4-kinase IIIbeta and proteins that bind
      and/or transfer phosphatidylinositol 4-phosphate (PtdIns-4P), such as oxysterol
      binding protein (OSBP) and ceramide transfer protein. Here, we investigated the
      consequences of PKD phosphorylation of OSBP at endoplasmic reticulum (ER)-Golgi
      membrane contact sites (MCS). Results with OSBP phospho-mutants revealed that PKD
      phosphorylation did not affect sterol and PtdIns-4P binding, activation of
      sphingomyelin (SM) synthesis at Golgi-ER MCS or other OSBP phospho-sites.
      Instead, an interaction was identified between the N-terminal region of OSBP and
      PKD1 that was independent of kinase activity and OSBP phosphorylation status.
      S916 autophosphorylation of PKD1 was inhibited by OSBP expression suggesting the
      interaction negatively regulates PKD1 activity. Stimulation of PKD1 activity by
      phorbol ester promoted the Golgi-localization of wild-type and phospho-mutants of
      OSBP but did not affect OSBP-dependent SM synthesis. Only when wild-type or
      kinase-dead PKD1 was overexpressed was 25-hydroxycholesterol-activated SM
      synthesis inhibited. We conclude that OSBP and PKD1 form a complex that inhibits
      both the oxysterol-dependent activity of OSBP at the ER-Golgi and activation of
      PKD1. Formation of the complex was independent of PKD1 activity and
      phosphorylation of OSBP.

PMID- 30101473
TI  - Loss of S100A1 expression leads to Ca2+ release potentiation in mutant mice with
      disrupted CaM and S100A1 binding to CaMBD2 of RyR1.
AB  - Calmodulin (CaM) and S100A1 fine-tune skeletal muscle Ca2+ release via opposite
      modulation of the ryanodine receptor type 1 (RyR1). Binding to and modulation of
      RyR1 by CaM and S100A1 occurs predominantly at the region ranging from amino acid
      residue 3614-3640 of RyR1 (here referred to as CaMBD2). Using synthetic peptides,
      it has been shown that CaM binds to two additional regions within the RyR1,
      specifically residues 1975-1999 and 4295-4325 (CaMBD1 and CaMBD3, respectively).
      Because S100A1 typically binds to similar motifs as CaM, we hypothesized that
      S100A1 could also bind to CaMBD1 and CaMBD3. Our goals were: (1) to establish
      whether S100A1 binds to synthetic peptides containing CaMBD1 and CaMBD3 using
      isothermal calorimetry (ITC), and (2) to identify whether S100A1 and CaM modulate
      RyR1 Ca2+ release activation via sites other than CaMBD2 in RyR1 in its native
      cellular context. We developed the mouse model (RyR1D-S100A1KO), which expresses
      point mutation RyR1-L3625D (RyR1D) that disrupts the modulation of RyR1 by CaM
      and S100A1 at CaMBD2 and also lacks S100A1 (S100A1KO). ITC assays revealed that
      S100A1 binds with different affinities to CaMBD1 and CaMBD3. Using high-speed
      Ca2+ imaging and a model for Ca2+ binding and transport, we show that the RyR1D
      S100A1KO muscle fibers exhibit a modest but significant increase in myoplasmic
      Ca2+ transients and enhanced Ca2+ release flux following field stimulation when
      compared to fibers from RyR1D mice, which were used as controls to eliminate any
      effect of binding at CaMBD2, but with preserved S100A1 expression. Our results
      suggest that S100A1, similar to CaM, binds to CaMBD1 and CaMBD3 within the RyR1,
      but that CaMBD2 appears to be the primary site of RyR1 regulation by CaM and
      S100A1.

PMID- 30101478
TI  - The Effect of Organizational Justice and Trust on Job Stress in Hospital
      Organizations.
AB  - PURPOSE: The primary purpose of this study was to explore the relationships among
      distributive justice, procedural justice, interactional justice, job stress,
      cognition-based trust, and affect-based trust; the secondary purpose was to
      determine the effect of distributive justice, procedural justice, interactional
      justice, cognition-based trust, and affect-based trust on job stress in hospital
      organizations. METHOD: Data were collected using scales of job stress,
      organizational justice, and organizational trust. The study was conducted in two
      public hospitals in Turkey. A total of 432 health personnel participated in this
      study. RESULTS: This study showed that both cognition-based trust and affect
      based trust were significantly positively correlated to the three dimensions of
      organizational justice (distributive justice, procedural justice, and
      interactional justice), but they were significantly negatively related to job
      stress. According to regression analysis, organizational justice was a
      significant predictor for job stress. CONCLUSIONS: In the working environment of
      hospitals, job stress and perceptions of organizational justice are significant
      variables that affect employees' working processes and their feelings of trust in
      their organization. CLINICAL RELEVANCE: Reducing employees' job stress and
      improving their perceptions of organizational trust and organizational justice
      can improve their levels of cognition-based trust and affect-based trust
      regarding their managers. As the job stress of nurses decreases, the
      effectiveness of health services may increase as organizational trust and justice
      develop.

PMID- 30101479
TI  - SRPK1 gene silencing promotes vascular smooth muscle cell proliferation and
      vascular remodeling via inhibition of the PI3K/Akt signaling pathway in a rat
      model of intracranial aneurysms.
AB  - OBJECTIVE: Intracranial aneurysm (IA) is a life threatening cerebrovascular
      disease characterized by phenotypic modulation of vascular smooth muscle cells
      (VSMCs) and loss of vessel cells. In addition to environmental factors, genetic
      factors have been proposed to be a critical factor in the onset and progression
      of IA. The present study investigates the effects of serine-arginine protein
      kinase 1 (SRPK1) on VSMC proliferation and apoptosis both in vivo and in vitro,
      as well as its role in vascular remodeling in vivo through PI3 K/Akt signaling in
      IA. METHODS: Differentially expressed genes related to IA were initially
      identified using microarray analysis. Immunohistochemistry was conducted to
      determine SRPK1 expression in the vascular walls in IA and normal cerebral
      vascular walls. TUNEL staining were applied to observe cell apoptosis patterns of
      VSMCs. VSMC proliferation and apoptosis in vitro were detected by cell counting
      kit-8 (CCK8) assay and flow cytometry. The expressions of SRPK1, PI3 K/Akt
      signaling pathway- and apoptosis-related genes were evaluated by RT-qPCR and
      Western blot analysis. RESULTS: Microarray data of GSE36791 and GSE54083 were
      analyzed to determine the selection of SRPK1 gene. The vascular walls in IA rat
      models produced high levels of SRPK1 expression and an activated PI3 K/Akt
      signaling pathway. VSMCs treated with siRNA-SRPK1 exhibited enhanced cell
      proliferation, repressed cell apoptosis, and increased vascular remodeling, all
      of which suggest the inhibition of the PI3 K/AKT pathway. Notably, PI3 K/AKT
      pathway reversed the effect of SRPK1 silencing. CONCLUSION: Our results show that
      siRNA-mediated silencing of SRPK1 gene inhibits VSMC apoptosis, and increases
      VSMCs proliferation and vascular remodeling in IA via the PI3 K/Akt signaling
      pathway. Our findings provide a novel intervention target for the molecular
      treatment of IA.

PMID- 30101480
TI  - Red muscle function and thermal acclimation to cold in rainbow smelt, Osmerus
      mordax, and rainbow trout, Oncorhynchus mykiss.
AB  - Climate change affects the thermal environment of aquatic organisms. Changes in
      the thermal environment may affect muscle function in the eurythermal rainbow
      smelt, Osmerus mordax, and relatively more stenothermal rainbow trout,
      Oncorhynchus mykiss. Literature suggests that the trout will be more sensitive to
      changes in environmental temperature, as they experience a more limited range of
      environmental temperatures. To examine the effects of thermal environment on red
      muscle function, both the smelt and trout were thermally acclimated to either a
      warm (12-15 degrees C) or cold (4-5 degrees C) temperature, after which studies
      of swimming performance and muscle mechanics were performed. The data on swimming
      performance and maximum muscle shortening velocity in rainbow smelt were
      previously published. In both species, cold-acclimated (CA) fish swam with a
      significantly faster maximum aerobic swimming speed than warm-acclimated fish,
      when tested at a common temperature of 10 degrees C. Similarly, CA smelt and
      trout had faster red muscle contraction kinetics. However, smelt displayed a
      greater shift in contractile properties, such as having a significant shift in
      maximum muscle shortening velocity that was not observed in trout. The smelt red
      muscle outperformed trout, with twitch and tetanic times of relaxation being
      significantly faster for CA smelt compared with CA trout, especially when
      contraction kinetics were tested at 2 degrees C. The smelt shows a greater
      thermal acclimation response compared with trout, with more robust increases in
      maximum swimming speed and faster muscle contractile properties. These
      differences in acclimation response may contribute to understanding how smelt and
      trout cope with climate change.

PMID- 30101481
TI  - A mimicked bacterial infection prolongs stopover duration in songbirds-but more
      pronounced in short- than long-distance migrants.
AB  - Migration usually consists of intermittent travel and stopovers, the latter being
      crucially important for individuals to recover and refuel to successfully
      complete migration. Quantifying how sickness behaviours influence stopovers is
      crucial for our understanding of migration ecology and how diseases spread.
      However, little is known about infections in songbirds, which constitute the
      majority of avian migrants. We experimentally immune-challenged autumn migrating
      passerines (both short- and long-distance migrating species) with a simulated
      bacterial infection. Using an automated radiotelemetry system in the stopover
      area, we subsequently quantified stopover duration, "bush-level" activity
      patterns (0.1-30 m) and landscape movements (30-6,000 m). We show that compared
      to controls, immune-challenged birds prolonged their stopover duration by on
      average 1.2 days in long-distance and 2.9 days in short-distance migrants,
      respectively (100%-126% longer than controls, respectively). During the prolonged
      stopover, the immune-challenged birds kept a high "bush-level" activity (which
      was unexpected) but reduced their local movements, independent of migration
      strategy. Baseline immune function, but not blood parasite infections prior to
      the immune challenge, had a prolonging effect on stopover duration, particularly
      in long-distance migrants. We conclude that a mimicked bacterial infection does
      not cause lethargy, per se, but restricts landscape movements and prolongs
      stopover duration, and that this behavioural response also depends on the status
      of baseline immune function and migration strategy. This adds a new level to the
      understanding of how acute inflammation affect migration behaviour and hence the
      ecology and evolution of migration. Accounting for these effects of bacterial
      infections will also enable us to fine-tune and apply optimal migration theory.
      Finally, it will help us predicting how migrating animals may respond to
      increased pathogen pressure caused by global change.

PMID- 30101482
TI  - The frequency of specific contact allergies is reduced in patients with
      psoriasis.
AB  - BACKGROUND: Earlier studies suggested an inverse association between contact
      allergy and psoriasis, although the results of clinical studies have been
      inconsistent. Gene expression studies in human contact allergy focusing on immune
      responses revealed nickel being an inducer of T helper (Th)1/Th17 and some Th22
      immune polarization, whereas fragrances were found to promote a Th2-dominated
      immune activation. OBJECTIVES: To investigate the epidemiological association
      between contact allergy and psoriasis in a large multicentre cohort and to
      analyse the sensitization profile to specific allergens in these patients.
      METHODS: Retrospective analysis of patch-tested patients from 56 departments of
      dermatology (1996-2015), including 2387 patients with psoriasis and 161 989
      control patients. All patients with atopic dermatitis were excluded from both
      groups. RESULTS: The odds ratio (OR) for contact allergy was calculated to be
      0.55 in patients with psoriasis (95% confidence interval 0.50-0.59). Logistic
      regression analyses with several independent variables indicated a 'protective
      effect' of having psoriasis for most allergens, independently of age, sex,
      affected body site and patch test indication. Fragrance mix II (OR 0.36) and
      lanolin alcohols (OR 0.38) were found to be among the least common allergens in
      patients with psoriasis. In contrast, the frequency of contact dermatitis to
      nickel was only marginally affected in patients with psoriasis compared with
      controls (OR 0.75). CONCLUSIONS: The inverse association between psoriasis and
      allergic contact sensitization is likely to be not exclusively mediated by
      psoriasis itself. The polarization of the activated immune response by specific
      allergens may influence the occurrence and significance of contact allergies in
      underlying immune-mediated diseases, eventually even beyond the skin.

PMID- 30101483
TI  - Bagged one-to-one matching for efficient and robust treatment effect estimation.
AB  - Observational studies present challenges due to bias from imbalance in baseline
      confounders. One-to-one matching (OOM), a popular cohort-construction technique
      for observational studies, reduces bias and provides a compelling basis for
      inference but generally leads to at least some loss of efficiency due to the
      exclusion of potentially informative subjects. We introduce the bagged one-to-one
      matching (BOOM) estimator, which combines the bias-reducing properties of OOM
      with the variance-reducing properties of bootstrap aggregation (bagging). We
      describe the BOOM algorithm in detail, provide R code for its implementation, and
      investigate its performance in simulation studies and a case study. In the
      simulation studies, under different types of model misspecification, we compare
      the BOOM estimator's performance in terms of mean squared error, bias, variance,
      accuracy of standard error estimation, and coverage of nominal 95% confidence
      intervals to that of OOM and to that of ordinary least squares estimation,
      inverse probability weighting, and targeted maximum likelihood estimation, all on
      the full unmatched cohort. In our simulations, the BOOM estimator achieves as
      much bias reduction as the estimator based on OOM, while having much lower
      variance. In all of the settings examined in the simulations, the BOOM's mean
      squared error is comparable to or better than that of the comparison methods. In
      the case study, BOOM yields estimates similar to those from the established
      methods, with narrower 95% confidence intervals.

PMID- 30101484
TI  - A radio-anatomical correlation study of the cisterna chyli.
AB  - Surgical laparoscopic procedures in the retroperitoneal and supramesocolic spaces
      are increasingly frequent. There is a high risk of iatrogenic intraoperative
      injury of the retroperitoneal lymphatic structures during these procedures. A
      precise understanding of the anatomy of the thoracic duct (TD) and the cisterna
      chyli (CC) is essential for safe surgical procedures in this area. However,
      routine imaging procedures rarely and often incorrectly visualize the CC. The
      objective of this study was to evaluate the feasibility of a retrograde injection
      of the TD to fill the CC with a contrast agent in 16 human cadavers. Both
      magnetic resonance lymphography (MRI) and computed tomography (CT) studies could
      be performed on the same anatomical specimen, using a contrast medium which
      hardened, allowing gross dissection. MRI and CT detectability were evaluated, and
      imaging results were compared with the anatomical dissection. The CC of 12/16
      cadavers were successfully injected, and four were unsuccessful due to technical
      difficulties, showing the effectiveness of the method. This technique can improve
      understanding of the anatomy of the TD and CC and provides an original option to
      study the complex anatomy of these structures by correlating precise cadaveric
      dissections with cross-sectional imaging.

PMID- 30101485
TI  - Bayesian semiparametric failure time models for multivariate censored data with
      latent variables.
AB  - In this paper, we propose a semiparametric failure time model to analyze
      multivariate censored data with latent variables. The proposed model generalizes
      the conventional accelerated failure time model to accommodate latent risk
      factors that could be measured by multiple observed variables through a factor
      analysis and to incorporate additive nonparametric functions of observed and
      latent risk factors to examine their functional effects on multivariate failure
      times of interest. A Bayesian approach, along with Bayesian P-splines and Markov
      chain Monte Carlo techniques, is developed to estimate the unknown parameters and
      functions. The empirical performance of the proposed methodology is evaluated by
      a simulation study. An application to a study on the risk factors of two diabetes
      complications is presented.

PMID- 30101487
TI  - Developing support strategies for burn care nurses through an understanding of
      their experiences: A meta-ethnographic study.
AB  - AIM: To build a comparative understanding of nurses' experiences with caring for
      burned patients with the goal of eliciting possible support strategies.
      BACKGROUND: Considering the stressful nature of burns nursing, there is a need to
      develop support strategies for burn care nurses. DESIGN: This meta-ethnographic
      study used Noblit and Hare's approach and followed PRISMA guidelines. DATA
      SOURCES: The search databases included PsycINFO, EbscoHost, Google Scholar,
      ScienceDirect, and PubMed from 1990 to 2017. REVIEW METHODS: Qualitative studies
      were included in the review if they examined burn care nurses' experiences. The
      Critical Appraisal Skills Programme quality assessment tool was used to appraise
      each study. RESULTS: Ten papers (six articles and four theses) published between
      1998 and 2014 met the criteria for inclusion. Three key concepts were generated
      from the synthesis: becoming a burns nurse, work environment, and nurses'
      emotional responses. The relationships between the concepts were noted to be
      reciprocal, from which a line of argument was developed using Schutz notion of
      constructs. CONCLUSION: There is a need to establish structures that can
      encourage burn care nurses to verbalise their feelings as well as strengthen the
      nursing team.

PMID- 30101486
TI  - Do health literacy and self-care behaviours affect quality of life in older
      persons with lung cancer receiving chemotherapy?
AB  - AIM: This study aimed at identifying the factors associated with health literacy,
      self-care behaviours, and quality of life among older persons with lung cancer
      receiving chemotherapy. METHODS: This was a descriptive study. A total of 80
      older persons with lung cancer receiving chemotherapy participated in this study.
      Data were collected from July 21 to November 3, 2016 in Korea. The Short Form of
      the Korean Functional Health Literacy Test, the Self-Care Behaviours Scale, and
      the Functional Assessment of Cancer Therapy Scale-Lung were used to measure
      functional health literacy, self-care behaviours, and quality of life,
      respectively. Stepwise multiple regression analyses were conducted to analyse the
      data. RESULTS: In the each regression model for the general and disease-related
      quality of life, performance status, self-care behaviours, and prior lines of
      treatment were identified as a predictor. However, functional health literacy was
      found to be a predictor only of disease-related quality of life. Among these
      predictors, self-care behaviours had the greatest impact. CONCLUSION: Health care
      providers should be aware of the effects of health literacy and self-care
      behaviours on health-related quality of life and consider the factors associated
      with quality of life when they take care of older persons with lung cancer
      receiving chemotherapy.

PMID- 30101488
TI  - Applying newer parameter Ret-He (reticulocyte haemoglobin equivalent) to assess
      latent iron deficiency (LID) in blood donors-study at a tertiary care hospital in
      India.
AB  - BACKGROUND: It is important to detect Latent Iron Deficiency (LID) to prevent
      development of an overt iron deficiency anemia. Early detection is difficult by
      using conventional hematological and biochemical parameters. Soluble transferrin
      receptor (sTfR) is presently the gold standard for diagnosing LID. We evaluated
      the utility of Reticulocyte Hemoglobin Equivalent (Ret-He), a newer hematological
      parameter, to predict LID in blood donors as compared to sTfR. METHODS: This was
      a randomized prospective study performed on 501 donor samples over a period of
      three-months. All donors were included after administering medical history
      questionnaire and a brief physical examination in accordance with national
      guidelines (Hb >=12.5). Additional samples were collected during donation
      according to the institutional standard operating procedure (SOP). All hemograms
      were performed on the Sysmex XE-2100 analyzer which included Ret-He. sTfR was
      measured in batch assays by ELISA (Biovendor, Czech Republic). Ret He <28 pg and
      sTfR>=3MUg/ml were used to diagnose LID. Serum Iron, Total Iron Binding Capacity
      (TIBC) and Serum Ferritin were also measured simultaneously. RESULTS: Of the 501
      blood donors, sTfR and Ret-He detected LID in 148 and 135 donors respectively. In
      comparison to sTfR, Ret-He had sensitivity of 92.7%, a specificity of 97.16%, PPV
      of 93.1% and NPV of 96.3%. Serum Ferritin, TIBC and serum Iron had comparatively
      lower sensitivity of 87.16%, 79.7% and 77.7% respectively. CONCLUSION: Ret-He can
      be used as a routine screening test to detect LID in blood donors. This could
      provide an opportunity to make appropriate and timely interventions like dietary
      changes or drug supplementation.

PMID- 30101489
TI  - Coexpression of 5-Aminolevulinic Acid Synthase Gene Facilitates Heterologous
      Production of Thermostable Cytochrome P450, CYP119, in Holo Form in Escherichia
      coli.
AB  - Cytochrome P450 enzymes are heme-containing monooxygenases that exhibit potential
      as biocatalysts for practical applications. The Escherichia coli expression
      system is frequently used for biocatalyst production; however, heterologous
      production of hemeproteins in their holo form is difficult due to insufficient
      heme synthesis by the host. In this study, 5-aminolevulinic acid synthase (ALAS)
      from Rhodobacter capsulatus is used to accelerate intracellular heme biosynthesis
      in E. coli; this demonstrates that coexpression of the ALAS gene (ALAS) improves
      the heterologous production of cytochrome P450, CYP119, from Sulfolobus
      acidocaldarius. Coexpression of ALAS increased the amount of heterologous CYP119
      isolated and the ratio of its holo form. The ratio of holo-CYP119 resulting from
      the coexpression of ALAS in E. coli was 99 %, whereas that from cells expressing
      CYP119 exclusively was 66 %. Coexpression of ALAS is a promising alternative for
      the efficient heterologous production of hemeproteins by using E. coli.

PMID- 30101490
TI  - Folliculotropic mycosis fungoides associated with GATA2 deficiency: a new skin
      manifestation.

PMID- 30101491
TI  - Why we continue to use the name Propionibacterium acnes.

PMID- 30101493
TI  - Digest: Disentangled bank: Less diverse urban environments modify the shape and
      magnitude of natural selection.
AB  - Urbanization provides a natural experiment for biologists to test how
      anthropogenic environmental change affects evolution in real time and frames
      predictions for anticipated evolutionary outcomes worldwide. Start et al. ()
      found that changes in species interactions (herbivore abundance and avian
      predation) along urbanization gradients predictably alter the shape and magnitude
      of natural selection on gall size (a defensive trait), suggesting that rapid
      global environmental change can alter species interactions, which may have
      foreseeable evolutionary consequences.

PMID- 30101492
TI  - Autism spectrum disorder symptoms from ages 2 to 19 years: Implications for
      diagnosing adolescents and young adults.
AB  - : This study explored change in social-communicative symptoms in 140 individuals
      with childhood autism spectrum disorder (ASD) diagnoses. Trajectories of
      caregiver-reported social-communicative symptoms were examined for three groups
      (verbal, delayed speech, minimally verbal) from ages 2 to 19 years. Groups showed
      comparable levels of social-communicative impairment at 2 years and significant
      decreases in overall symptom levels across the 17-year period (P < .001). Across
      three subdomains, main effects of time and language (P < .001) reflected patterns
      of overall improvement, although children with more impaired language tended to
      have more caregiver-reported symptoms relative to verbal peers. A significant
      time-by-language interaction (P < .001) reflected that trajectories of
      socioemotional reciprocity symptoms differed according to patterns of language
      development. In contrast, improvements in the nonverbal communication domain were
      seen across language groups, whereas deficits in the development and maintenance
      of relationships improved for only verbal children. Verbal adults showed
      significant reductions in the prevalence of kseveral symptoms exhibited during
      childhood. Improvements suggest that symptoms indicative of ASD in young children
      may no longer be diagnostic markers in adolescents and adults. Relative stability
      of several items suggests that impaired facial expression may be a core ASD
      symptom that warrants more systematic study across the lifespan. Research
      investigating the manifestation of ASD in older individuals is needed to foster
      development of appropriate assessment tools and interventions. Differential
      relationships to developmental factors within the broader social-communication
      domain underscores a need to focus on more narrowly defined symptom constructs
      when exploring links between pathophysiology and observable phenotypes. LAY
      SUMMARY: In a sample of 140 participants with autism spectrum disorder (ASD)
      followed from 2 to 19 years old, this study found that overall social
      communicative symptoms improve across childhood and adolescence. However, timing
      and amount of change varied for different symptom categories and participants
      with different language abilities. Findings suggest that some older adolescents
      and adults with ASD may not exhibit the same difficulties observed in young
      children with ASD. More research is needed to better understand the strengths and
      needs of young adults with ASD.

PMID- 30101494
TI  - Genetic and molecular evidence that brown trout Salmo trutta belonging to the
      Danubian lineage are a single biological species.
AB  - We tested for reproductive isolation between Salmo trutta abanticus, S.t. labrax,
      S.t. caspius and S.t. fario by conducting crosses to produce F1 and F2 offspring.
      We also estimated the extent of genetic divergence between all three entities by
      examining sequence variation across the coI, d-loop and cytb mitochondrial genes.
      All of the F1 cross-types were successfully produced. After 2 years of culturing,
      F2 generation were produced as well. Fertilization, hatching and survival rates
      and hatching performance of F1 and F2 generations were evaluated. F2 generation
      had similar performance to their parent. Fertilization, hatching, larval survival
      rate and hatchery performance of F1 and F2 generation were similar except pure
      bred F2 S.t. abanticus. Purebred F1 individuals shared similar coloration
      patterns and spots with their parents but direction of the hybridization appeared
      to be decisive on morphology of hybrids. Some of the hybrids exhibit different
      morphological characters than their parents. Based on partial alignments of the
      three genes, phylogenetic analysis showed that these S. trutta are gathering
      within the same clade and appeared as monophyletic group. We found that there
      were some morphologic and genetic variation among S. trutta subspecies but the
      degree of variation does not warrant species level recognition. These findings
      indicate that the four subspecies constitute a single biological entity,
      corresponding to different morphs of the Danubian lineage. We therefore recommend
      that S. trutta belonging to Danubian lineage in Turkey be referred to as Salmo
      trutta and that strains be named according to location, such as Abant, Caspian,
      Black Sea and Anatolian.

PMID- 30101496
TI  - Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs.
AB  - Over the past decades, a multitude of experimental drugs have been shown to delay
      disease progression in preclinical animal models of amyotrophic lateral sclerosis
      (ALS) but failed to show efficacy in human clinical trials or are still waiting
      for approval under Phase I-III trials. Riluzole, a glutamatergic
      neurotransmission inhibitor, is the only drug approved by the USA Food and Drug
      Administration for ALS treatment with modest benefits on survival. Recently, an
      antioxidant drug, edaravone, developed by Mitsubishi Tanabe Pharma was found to
      be effective in halting ALS progression during early stages. The newly approved
      drug edaravone is a force multiplier for ALS treatment. This short report
      provides an overview of the two drugs that have been approved for ALS treatment
      and highlights an update on the timeline of drug development, how clinical trials
      were done, the outcome of these trials, primary endpoint, mechanism of actions,
      dosing information, administration, side effects, and storage procedures.
      Moreover, we also discussed the pressing issues and challenges of ALS clinical
      trials and drug developments as well as future outlook.

PMID- 30101495
TI  - Ultralow Dispersion Multicomponent Thin-Film Chalcogenide Glass for Broadband
      Gradient-Index Optics.
AB  - A novel photothermal process to spatially modulate the concentration of sub
      wavelength, high-index nanocrystals in a multicomponent Ge-As-Pb-Se chalcogenide
      glass thin film resulting in an optically functional infrared grating is
      demonstrated. The process results in the formation of an optical nanocomposite
      possessing ultralow dispersion over unprecedented bandwidth. The spatially
      tailored index and dispersion modification enables creation of arbitrary
      refractive index gradients. Sub-bandgap laser exposure generates a Pb-rich
      amorphous phase transforming on heat treatment to high-index crystal phases.
      Spatially varying nanocrystal density is controlled by laser dose and is
      correlated to index change, yielding local index modification to ~+0.1 in the mid
      infrared.

PMID- 30101497
TI  - Effect of parasite dose and host age on the infection with Besnoitia besnoiti
      tachyzoites in cattle.
AB  - Bovine besnoitiosis is continuing to spread in Europe. Therefore, the development
      of ruminant animal models of infection is urgently needed to evaluate therapeutic
      and prophylactic tools. Herein, we studied the effect of parasite dose and host
      age on the infection dynamics with Besnoitia besnoiti tachyzoites in cattle in
      two independent experimental infections. In experiment A, twelve 3-month-old male
      calves were inoculated intravenously with either three different doses of
      tachyzoites (G1: 108 ; G2: 107 ; G3: 106 ) or with PBS (G4). In experiment B, six
      14-month-old bulls were inoculated with 106 tachyzoites based on results obtained
      in experiment A. In both trials, clinical signs compatible with acute and chronic
      besnoitiosis were monitored daily; blood and skin samples were collected
      regularly for 70-115 days post-infection (pi). Finally, animals were killed, and
      tissues were collected for lesion and parasite detections. Infected animals
      developed mild-moderate signs compatible with acute besnoitiosis. Lymphadenopathy
      and fever were observed in both calves (from 12 hr until 7 days pi) and bulls
      (from 6 days until 9 days pi). Seroconversion was detected at 16-19 days pi, and
      antibody levels remained high. Infected animals did not developed characteristic
      clinical signs and macroscopic lesions of chronic besnoitiosis. However,
      successfully, parasite-DNA was detected in a reduced number of target tissues:
      conjunctiva, ocular sclera, epididymis, skin of the scrotum and carpus in calves
      (n = 10, 6 of which belonged to G3), and pampiniform plexus and testicular
      parenchyma in bulls. Remarkably, one tissue cyst and mild microscopic lesions
      were also detected. In summary, inoculated animals developed the acute
      besnoitiosis and chronic infection was evidenced by microscopic findings.
      However, our results suggest that tachyzoite dose and host age are not key
      variables for inducing clinical signs and macroscopic lesions characteristic of
      chronic besnoitiosis. Thus, a further refinement of this model should evaluate
      other parasite- and host-dependent variables.

PMID- 30101498
TI  - The role of compensation in explaining harmful effects of overtime work on self
      reported heart disease: Preliminary evidence from a Germany prospective cohort
      study.
AB  - BACKGROUND: Research evidence suggests harmful effects of overtime work on risk
      of heart disease. However, whether withdrawing compensation for overtime work
      (time-off or money) provides a relevant explanation of this association has not
      been explored. METHODS: Using cohort data, we included 6345 employees from
      Germany (3079 men and 3266 women), and applied Poisson regression analysis to
      examine the prospective association of overtime work without compensation with
      risk of self-reported incident heart disease over 2 years. RESULTS: Uncompensated
      overtime work was associated with an elevated risk of heart disease after
      adjustment for relevant variables (RR = 1.85, 95%CI: 1.05-3.25), compared to no
      overtime work. Stratified analyses indicated particularly strong effects among
      women and among employees with low socioeconomic position. CONCLUSIONS: In line
      with the stress-theoretical model of effort-reward imbalance at work, these
      findings document an important role of compensation on heart disease in the frame
      of overtime work.

PMID- 30101499
TI  - Endoscopic findings corresponding to multiple Lugol-voiding lesions in the
      esophageal background mucosa.
AB  - BACKGROUND AND AIM: Multiple Lugol-voiding lesions (LVLs) on Lugol
      chromoendoscopy can predict the development of metachronous multiple cancers in
      the esophagus and the head and neck regions. However, Lugol chromoendoscopy
      sometimes causes adverse events such as chest pain and discomfort. We therefore
      investigated the endoscopic findings on narrow band imaging (NBI) or blue laser
      imaging (BLI) that correspond to the presence of multiple LVLs in patients with
      esophageal squamous cell carcinoma. METHODS: First, we investigated the NBI/BLI
      findings corresponding to individual small LVLs (one-to-one correspondence).
      Second, we investigated the association between the grade of multiple LVLs and
      the five endoscopic findings, including multiple foci of dilated vessels (MDV),
      multiple small brownish areas without microvascular irregularity, and a
      nonuniform color tone. RESULTS: One-to-one correspondence of endoscopic findings
      was analyzed in 106 small LVLs. The main findings matched with small LVLs were a
      focus of dilated vessels (44 lesions), a small brownish area (17 lesions), and a
      small brownish area with a focus of dilated vessels (19 lesions). The
      relationship between multiple LVLs and each finding assessed by NBI/BLI was
      assessed in 155 patients. Multivariate logistic regression indicated that the
      presence of MDV was the only finding independently associated with multiple LVLs
      (P < 0.01). CONCLUSIONS: The presence of MDV in the noncancerous background
      esophageal mucosa was significantly associated with multiple LVLs. This pilot
      study demonstrates that MDV has the potential to be a new risk factor for the
      development of metachronous multiple esophageal squamous cell carcinoma.

PMID- 30101500
TI  - Both maternal care received and genotype influence stress-related phenotype in
      female rats.
AB  - Rat dams differ naturally in the level of maternal care they provide to their
      offspring within the same litter. We explored possible mechanisms of differential
      maternal care focused on genetic variation. We examined single nucleotide
      polymorphisms in the glucocorticoid receptor, FK506-binding protein, and
      serotonin transporter genes in two separate cohorts, and the relationship between
      differential maternal care received, genotype, and offspring phenotype. Allelic
      variation in all three genes was significantly associated with levels of maternal
      care received by offspring and behavioral and endocrine stress responses in
      adulthood. Differences in pup behavior were also associated with allelic
      variation in these genes. Together, these results indicate that the dam/pup
      interaction is dynamic and implicate the genotype of the offspring in influencing
      the level of maternal care received. They further suggest that some genotypes may
      have a dampening effect on the impact of maternal care on stress-related
      phenotypes in adulthood.

PMID- 30101502
TI  - Genetics of metabolic traits in Greenlanders: lessons from an isolated
      population.
AB  - In this review, we describe the extraordinary population of Greenland, which
      differs from large outbred populations of Europe and Asia, both in terms of
      population history and living conditions. Many years in isolation, small
      population size and an extreme environment have shaped the genetic composition of
      the Greenlandic population. The unique genetic background combined with the
      transition from a traditional Inuit lifestyle and diet, to a more Westernized
      lifestyle, has led to an increase in the prevalence of metabolic conditions like
      obesity, where the prevalence from 1993 to 2010 has increased from 16.4% to 19.4%
      among men, and from 13.0% to 25.4% among women, type 2 diabetes and
      cardiovascular diseases. The genetic susceptibility to metabolic conditions has
      been explored in Greenlanders, as well as other isolated populations, taking
      advantage of population-genetic properties of these populations. During the last
      10 years, these studies have provided examples of loci showing evidence of
      positive selection, due to adaption to Arctic climate and Inuit diet, including
      TBC1D4 and FADS/CPT1A, and have facilitated the discovery of several loci
      associated with metabolic phenotypes. Most recently, the c.2433-1G>A loss-of
      function variant in ADCY3 associated with obesity and type 2 diabetes was
      described. This locus has provided novel biological insights, as it has been
      shown that reduced ADCY3 function causes obesity through disrupted function in
      primary cilia. Future studies of isolated populations will likely provide further
      genetic as well as biological insights.

PMID- 30101501
TI  - Tundra landscape heterogeneity, not interannual variability, controls the decadal
      regional carbon balance in the Western Russian Arctic.
AB  - Across the Arctic, the net ecosystem carbon (C) balance of tundra ecosystems is
      highly uncertain due to substantial temporal variability of C fluxes and to
      landscape heterogeneity. We modeled both carbon dioxide (CO2 ) and methane (CH4 )
      fluxes for the dominant land cover types in a ~100-km2 sub-Arctic tundra region
      in northeast European Russia for the period of 2006-2015 using process-based
      biogeochemical models. Modeled net annual CO2 fluxes ranged from -300 g C m-2 
      year-1 [net uptake] in a willow fen to 3 g C m-2  year-1 [net source] in dry
      lichen tundra. Modeled annual CH4 emissions ranged from -0.2 to 22.3 g C m-2 
      year-1 at a peat plateau site and a willow fen site, respectively. Interannual
      variability over the decade was relatively small (20%-25%) in comparison with
      variability among the land cover types (150%). Using high-resolution land cover
      classification, the region was a net sink of atmospheric CO2 across most land
      cover types but a net source of CH4 to the atmosphere due to high emissions from
      permafrost-free fens. Using a lower resolution for land cover classification
      resulted in a 20%-65% underestimation of regional CH4 flux relative to high
      resolution classification and smaller (10%) overestimation of regional CO2 uptake
      due to the underestimation of wetland area by 60%. The relative fraction of
      uplands versus wetlands was key to determining the net regional C balance at this
      and other Arctic tundra sites because wetlands were hot spots for C cycling in
      Arctic tundra ecosystems.

PMID- 30101504
TI  - Integrated Functional High-Strength Hydrogels with Metal-Coordination Complexes
      and H-Bonding Dual Physically Cross-linked Networks.
AB  - With the deepening of research on high-strength hydrogels, the multi-functional
      study of hydrogels has become a hot spot. In this paper, a dual cross-linked
      physical high-strength hydrogels is prepared by a relatively simple method. 2
      Vinyl- 4,6-Diamino-2-vinyl-1,3,5-triazine (VDT) induces the formation of the
      first cross-linking points through the interaction of hydrogen bonds with
      poly(acrylamide-co-acrylic acid) (PAm-co-Ac) chains, then the secondary physical
      cross-linkers Fe3+ that introduce ionic coordinates between Fe3+ and -COO-
      groups. Due to the synergistic effect of hydrogen bonding and ionic coordination,
      hydrogels possess high tensile strength (approx. 4.34 MPa), large elongation
      (approx. 17.64 times), and good healing properties under alkali solution after
      cutting into two pieces. Meanwhile, VDT contains diaminotriazine functional
      groups that easily form hydrogen bonds so that the polymer of hydrogels could
      absorb 5-fluorouridine. In addition, the contribution of ionic polymer segments
      enables pH to be sensitive to hydrogels and facilitates the adsorption of a large
      number of ionic monomers to form ionic conductive networks, the prepared hydrogel
      capacitor device has very high sensitivity to pressure and deformation, and can
      detect the movement behavior of the human body. The dual-physical cross-linked
      hydrogels had a selective adsorption to biological small molecules and could be
      assembled into a flexible wearable device with high sensitivity.

PMID- 30101505
TI  - Hypoxic environment protects cowpea bruchid (Callosobruchus maculatus) from
      electron beam irradiation damage.
AB  - BACKGROUND: Electron beam (eBeam) irradiation and hermetic storage are safe and
      effective technologies to protect stored products. Although hypoxic environment
      improves performance of some irradiated insects, whether hypoxia affects
      irradiation of storage insects and impacts pest control efficacy remains to be
      investigated. RESULTS: Using cowpea bruchid (Callosobruchus maculatus) larvae, we
      showed that, relative to eBeam irradiation under normoxia, the adult emergence
      rate increased substantially if they were exposed to hypoxia prior to and during
      eBeam treatment. Conversely, exposure to hypoxia only after eBeam irradiation did
      not have this protective effect. eBeam irradiation caused an increase in reactive
      oxygen species (ROS) in normoxic larvae but not in hypoxic larvae. The activity
      of citrate synthase, a pace-making enzyme in the citric acid cycle, was
      suppressed under hypoxia but resumed normal function within hours of
      reoxygenation, suggesting that reduced mitochondrial activity, and thus less ROS
      production under hypoxia increased insect tolerance to irradiation. Furthermore,
      reoxygenation accelerated eBeam-induced glutathione-S-transferase activation and
      potentiated eBeam-enhanced catalase activities. Faster and stronger
      detoxification capacity in eBeam-irradiated, hypoxic larvae may have protected
      them from oxidative damage. CONCLUSION: Hypoxic environment enhanced
      radiotolerance of bruchid larvae, presumably due to limited ROS production and
      elevated antioxidant enzymatic activities after reoxygenation. (c) 2018 Society
      of Chemical Industry.

PMID- 30101506
TI  - The central effects of buspirone on abdominal pain in rats.
AB  - BACKGROUND: Buspirone, a partial agonist of the 5-HT1a receptor (5-HT1a R), owing
      to potential antinociceptive properties may be useful in treatment of abdominal
      pain in IBS patients. The pain-related effects of buspirone are mediated via the
      5-HT1a Rs, specifically located within the ventrolateral medulla (VLM). The most
      animal studies of the 5-HT1a R involvement in pain control have been carried out
      with somatic behavioral tests. The 5-HT1a R contribution in visceral pain
      transmission within the VLM is unclear. The objective of our study was to
      evaluate the 5-HT1a R contribution in abdominal pain transmission within the VLM.
      METHODS: Using animal model of abdominal pain (urethane-anaesthetized rats),
      based on the noxious colorectal distension (CRD) as pain stimulus we studied
      effects of buspirone (1.0-4.0 mg kg-1 , iv) on the CRD-induced VLM neuron and
      blood pressure responses as markers of abdominal pain before and after the 5-HT1a
      R blockade by antagonist, WAY 100,635. RESULTS: The CRD induced a significant
      increase in VLM neuron activity up to 201.5 +/- 18.0% and depressor reactions up
      to 68 +/- 1.8% of baseline. Buspirone (1.0-4.0 mg kg-1 , iv) resulted in an
      inhibition of the CRD-induced neuron responses which were changed inversely with
      dose increase and decreased depressor reactions directly with dose increase.
      These effects were antagonized by intracerebroventricular WAY 100,635.
      CONCLUSION: Buspirone exerts complex biphasic action on the pain-related VLM
      neuron activity inversely depending on dose. The final effect of buspirone
      depends on the functional balance between of activation the pre- and postsynaptic
      5-HT1a Rs in mediating pain control networks.

PMID- 30101503
TI  - Effects of interspecific coexistence on laying date and clutch size in two
      closely related species of hole-nesting birds.
AB  - Coexistence between great tits Parus major and blue tits Cyanistes caeruleus, but
      also other hole-nesting taxa, constitutes a classic example of species co
      occurrence resulting in potential interference and exploitation competition for
      food and for breeding and roosting sites. However, the spatial and temporal
      variations in coexistence and its consequences for competition remain poorly
      understood. We used an extensive database on reproduction in nest boxes by great
      and blue tits based on 87 study plots across Europe and Northern Africa during
      1957-2012 for a total of 19,075 great tit and 16,729 blue tit clutches to assess
      correlative evidence for a relationship between laying date and clutch size,
      respectively, and density consistent with effects of intraspecific and
      interspecific competition. In an initial set of analyses, we statistically
      controlled for a suite of site-specific variables. We found evidence for an
      effect of intraspecific competition on blue tit laying date (later laying at
      higher density) and clutch size (smaller clutch size at higher density), but no
      evidence of significant effects of intraspecific competition in great tits, nor
      effects of interspecific competition for either species. To further control for
      site-specific variation caused by a range of potentially confounding variables,
      we compared means and variances in laying date and clutch size of great and blue
      tits among three categories of difference in density between the two species. We
      exploited the fact that means and variances are generally positively correlated.
      If interspecific competition occurs, we predicted a reduction in mean and an
      increase in variance in clutch size in great tit and blue tit when density of
      heterospecifics is higher than the density of conspecifics, and for intraspecific
      competition, this reduction would occur when density of conspecifics is higher
      than the density of heterospecifics. Such comparisons of temporal patterns of
      means and variances revealed evidence, for both species, consistent with
      intraspecific competition and to a smaller extent with interspecific competition.
      These findings suggest that competition associated with reproductive behaviour
      between blue and great tits is widespread, but also varies across large spatial
      and temporal scales.

PMID- 30101507
TI  - Individual participant data meta-analysis of continuous outcomes: A comparison of
      approaches for specifying and estimating one-stage models.
AB  - One-stage individual participant data meta-analysis models should account for
      within-trial clustering, but it is currently debated how to do this. For
      continuous outcomes modeled using a linear regression framework, two competing
      approaches are a stratified intercept or a random intercept. The stratified
      approach involves estimating a separate intercept term for each trial, whereas
      the random intercept approach assumes that trial intercepts are drawn from a
      normal distribution. Here, through an extensive simulation study for continuous
      outcomes, we evaluate the impact of using the stratified and random intercept
      approaches on statistical properties of the summary treatment effect estimate.
      Further aims are to compare (i) competing estimation options for the one-stage
      models, including maximum likelihood and restricted maximum likelihood, and (ii)
      competing options for deriving confidence intervals (CI) for the summary
      treatment effect, including the standard normal-based 95% CI, and more
      conservative approaches of Kenward-Roger and Satterthwaite, which inflate CIs to
      account for uncertainty in variance estimates. The findings reveal that, for an
      individual participant data meta-analysis of randomized trials with a 1:1
      treatment:control allocation ratio and heterogeneity in the treatment effect, (i)
      bias and coverage of the summary treatment effect estimate are very similar when
      using stratified or random intercept models with restricted maximum likelihood,
      and thus either approach could be taken in practice, (ii) CIs are generally best
      derived using either a Kenward-Roger or Satterthwaite correction, although
      occasionally overly conservative, and (iii) if maximum likelihood is required, a
      random intercept performs better than a stratified intercept model. An
      illustrative example is provided.

PMID- 30101508
TI  - How Do Creative Experts Practice New Skills? Exploratory Practice in
      Breakdancers.
AB  - How do expert performers practice as they develop creatively? This study
      investigated the processes involved in the practice of new skills by expert
      breakdancers. A great deal of evidence supports the theory of "deliberate
      practice" (Ericsson, Krampe, & Tesch-Romer, 1993, Psychological Review, 100, 363)
      in skill acquisition; however, expert creative performers may emphasize other
      forms of practice for skill development. Four case studies collected through
      fieldwork and laboratory observation were analyzed to evaluate expert dancers'
      practice processes as they developed proficiency in new, specific skills. We
      focused on three aspects of learning: the degree of skill acquisition, the
      content of skills included in practice, and dancers' stated purposes for
      practicing. The results showed that dancers' practice improved skills (as
      suggested by deliberate practice) and engaged the exploration of new, original
      skills, along with coordinating skills within performance. In their practice,
      these dance experts went beyond deliberative practice to highly exploratory
      processes for skill development.

PMID- 30101509
TI  - What does the grey matter decrease in the medial prefrontal cortex reflect in
      people with chronic pain?
AB  - BACKGROUND AND OBJECTIVE: Alterations in the grey matter volume of several brain
      regions have been reported in people with chronic pain. The most consistent
      observation is a decrease in grey matter volume in the medial prefrontal cortex.
      These findings are important as the medial prefrontal cortex plays a critical
      role in emotional and cognitive processing in chronic pain. Although a logical
      cause of grey matter volume decrease may be neurodegeneration, this is not
      supported by the current evidence. Therefore, the purpose of this review was to
      evaluate the existing literature to unravel what the decrease in medial
      prefrontal cortex grey matter volume in people with chronic pain may represent on
      a biochemical and cellular level. DATABASES AND DATA TREATMENT: A literature
      search for this topical review was conducted using PubMed and SCOPUS library.
      Search terms included chronic pain, pain, medial prefrontal cortex, anterior
      cingulate cortex, grey matter, neurochemistry, spectroscopy, magnetic resonance
      imaging, positron emission tomography, dendrite, neurodegeneration, glia,
      astrocyte, microglia, neurotransmitter, glutamate, GABA and different
      combinations of these terms. RESULTS: Adopting a stress model of chronic pain,
      two major pathways are proposed that contribute to grey matter volume decrease in
      the medial prefrontal cortex: (a) changes in dendritic morphology as a result of
      hypothalamic-pituitary axis dysfunction and (b) neurotransmitter dysregulation,
      specifically glutamate and gamma-Aminobutyric acid, which affects local
      microvasculature. CONCLUSION: Our model proposes new mechanisms in chronic pain
      pathophysiology responsible for mPFC grey matter loss as alternatives to
      neurodegeneration. SIGNIFICANCE: It is unclear what the decrease in medial
      prefrontal cortex grey matter volume represents in chronic pain. The most
      attractive reason is neurodegeneration. However, there is no evidence to support
      this. Our review reveals nondegenerative causes of decreased medial prefrontal
      grey matter to guide future research into chronic pain pathophysiology.

PMID- 30101510
TI  - The impact of food order on postprandial glycaemic excursions in prediabetes.
AB  - Data suggest that nutrient order during a meal significantly impacts postprandial
      glucose and insulin excursions in type 2 diabetes, while its effects in
      prediabetes have not been reported. Fifteen participants with prediabetes
      consumed the same meal on 3 days in random order: carbohydrate first, followed 10
      minutes later by protein and vegetables (CF); protein and vegetables first,
      followed 10 minutes later by carbohydrate (PVF); or vegetables first followed by
      protein and carbohydrate (VF). Blood was sampled for glucose and insulin
      measurements at 0, 30, 60, 90, 120, 150 and 180 minutes. Incremental glucose
      peaks were similarly attenuated by >40% in the PVF and VF meal conditions
      compared with CF. The incremental area under the curve for glucose was 38.8%
      lower following the PVF meal order, compared with CF, and postprandial insulin
      excursions were significantly lower in the VF meal condition compared with CF.
      The CF meal pattern showed marked glycaemic variability whereas glucose levels
      were stable in the PVF and VF meal conditions. Food order presents a novel,
      simple behavioural strategy to reduce glycaemic excursions in prediabetes.

PMID- 30101511
TI  - Regioselective Metal- and Reagent-Free Arylation of Benzothiophenes by
      Dehydrogenative Electrosynthesis.
AB  - A novel strategy for the synthesis of biaryls consisting of a benzothiophene and
      a phenol moiety is reported. These heterobiaryls are of utmost interest for
      pharmaceutical, biological, and high-performance optoelectronic applications. The
      metal- and reagent-free, electrosynthetic, and highly efficient method enables
      the generation of 2- and 3-(hydroxyphenyl)benzo[b]thiophenes in a regioselective
      fashion. The described one-step synthesis is easy to conduct, scalable, and
      inherently safe. The products are afforded in high yields of up to 88 % and with
      exquisite selectivity. The reaction also features a broad scope and tolerates a
      large variety of functional groups.

PMID- 30101512
TI  - Supramolecular Peptide/Polymer Hybrid Hydrogels for Biomedical Applications.
AB  - Peptides and polymers are the "elite" building blocks in hydrogel fabrication
      where the typical approach consists of coupling specific peptide sequences (cell
      adhesive and/or enzymatically cleavable) to polymer chains aiming to obtain
      controlled cell responses (adhesion, migration, differentiation). However, the
      use of polymers and peptides as structural components for fabricating
      supramolecular hydrogels is less well established. Here, the literature on the
      design of peptide/polymer systems for self-assembly into hybrid hydrogels, as
      either peptide-polymer conjugates or combining both components individually, is
      reviewed. The properties (stiffness, mesh structure, responsiveness, and
      biocompatibility) of the hydrogels are then discussed from the viewpoint of their
      potential biomedical applications.

PMID- 30101514
TI  - Hong Kong consumer preferences for Japanese beef: Label knowledge and reference
      point effects.
AB  - The excellent flavor of Wagyu is becoming increasingly popular all over the
      world. However, the popularity of Wagyu has encouraged competition for authentic
      Japanese Wagyu, resulting in the appearance of inauthentic Wagyu beef. To ward
      off this export competition, Japanese Wagyu producers need to improve and
      differentiate their value-added beef. As hardly any past studies focus on the
      consumption of Japanese Wagyu in Hong Kong, this paper uses a choice experiment
      to examine the valuation of beef by Hong Kong consumers in terms of country of
      origin. Data from 250 Hong Kong consumers obtained through a web questionnaire
      were used to analyze the beef preferences. In addition to the beef's country of
      origin, its marbling level, the Japanese Wagyu label and reference point effects
      were considered. The results indicate that Hong Kong consumers place a
      significant premium on Japanese Wagyu over Australian or American Wagyu. That
      premium is greater among consumers who have seen the Japanese Wagyu label.
      Reference price effects were also statistically confirmed. To promote Japanese
      Wagyu beef consumption, therefore, it is important to make the consumer aware of
      the advantages of Japanese Wagyu.

PMID- 30101516
TI  - Safe haven under constant attack-The Chlamydia-containing vacuole.
AB  - Chlamydia belong to the group of obligate intracellular bacteria that reside in a
      membrane bound vacuole during the entire intracellular phase of their life cycle.
      This vacuole called inclusion shields the bacteria from adverse influences in the
      cytosol of the host cell like the destructive machinery of the cell-autonomous
      defence system. The inclusion thereby prevents the digestion and eradication in
      specialised compartments of the intact and viable cell called phagolysosomes or
      autophagolysosomes. It is becoming more and more evident that keeping the
      inclusion intact also prevents the onset of cell intrinsic cell death programmes
      that are activated upon damage of the inclusion and direct the cell to destruct
      itself and the pathogen inside. Chlamydia secrete numerous proteins into the
      inclusion membrane to protect and stabilise their unique niche inside the host
      cell. We will focus in this review on the diverse attack strategies of the host
      aiming at the destruction of the Chlamydia-containing inclusion and will
      summarise the current knowledge on the protection mechanisms elaborated by the
      bacteria to maintain the integrity of their replication niche.

PMID- 30101515
TI  - Type 1 diabetes outcomes: Does distance to clinic matter?
AB  - BACKGROUND AND OBJECTIVES: To access care, pediatric type 1 diabetes (T1D)
      patients living in British Columbia (BC), Canada, travel to the sole tertiary
      pediatric hospital (BC Children's Hospital; BCCH), or they receive community care
      from pediatric endocrinologists and/or pediatricians. We sought to determine
      whether hemoglobin A1C (HbA1C ) and patient-reported outcomes were associated
      with (1) distance to clinic and (2) tertiary vs community care. METHODS: Patients
      were recruited from T1D clinics across BC. Clinical chart review and patient
      surveys were completed, including the Diabetes Treatment Satisfaction
      Questionnaire (DTSQ). Clinic type was categorized as tertiary (BCCH) or
      community, and the travel time to BCCH was categorized as <1 hour, 1 to 2 hours,
      or >2 hours. RESULTS: There were 189 participants. Age and duration of T1D were
      similar across groups. Mean number of visits/year for BCCH groups were 2.23,
      2.24, and 2.05 for the <1-hour, 1- to 2-hour, and >2-hour groups, respectively,
      vs 3.26 for the community group. Adjusted mean difference in HbA1C was +0.65%
      (95% confidence interval [CI]: 0.15, 1.15) and +0.52% (95% CI: 0.02, 1.02) for
      the BCCH >2-hour group compared to the BCCH <1-hour group and community groups,
      respectively. Child DTSQ scores were significantly lower in the BCCH >2-hour
      group compared to the BCCH <1-hour and community groups. CONCLUSIONS: Children
      traveling >2 hours to T1D clinic at BCCH had significantly higher HbA1C values
      and lower satisfaction with care vs those traveling <1 hour to BCCH and those
      receiving community care. Access to care closer to home may benefit glycemic
      control in children with T1D and improve treatment satisfaction. Future research
      should determine whether these findings can be replicated in other regions.

PMID- 30101513
TI  - Positive predictive values of fecal immunochemical tests used in the STOP CRC
      pragmatic trial.
AB  - Annual fecal immunochemical testing (FIT) is cost-effective for colorectal cancer
      (CRC) screening. However, FIT positivity rates and positive predictive value
      (PPV) can vary substantially, with false-positive (FP) results adding to
      colonoscopy burden without improving cancer detection. Our objective was to
      describe FIT PPV and the factors associated with FP results among patients
      undergoing CRC screening. In an ongoing pragmatic clinical trial of mailed-FIT
      outreach, clinics delivered one of three FIT brands (InSure, OC-Micro, and
      Hemosure). Patients who had a positive FIT result and a follow-up colonoscopy
      were included in this analysis (N = 1130). Patients' demographic and medical
      histories were abstracted from electronic health records (EHR). Associations with
      a FP result (ie, a positive FIT result with no evidence of advanced neoplasia
      during follow-up colonoscopy) were evaluated for FIT brand and patient factors
      using mixed-effects multivariable logistic regression. The mean proportion of FIT
      positive results ranged from 8% in centers using the OC-Micro test to 21% for
      Hemosure. PPVs for advanced neoplasia were 0.30 to 0.17, respectively (P for chi2
      = 0.08). In multivariable-adjusted models, use of Hemosure was associated with
      greater odds of a FP result than OC-Micro (OR = 2.00, 95% CI: 0.47-8.56) or
      InSure (OR = 1.72, 95% CI: 0.44-6.68). However, only female sex (OR = 1.58, 95%
      CI: 1.19-2.10) and history of a colorectal condition (OR = 2.17, 95% CI: 1.13
      4.15) were significantly associated with FP. In conclusion, FIT positivity varied
      by brand, and FP results differed by patient factors available through the EHR.
      These results can be used to minimize the frequency of FP results, reducing
      patient distress and colonoscopy burden.

PMID- 30101517
TI  - A rapid and sensitive method for the quantitative analysis of ibuprofen and its
      metabolites in equine urine samples by gas chromatography with tandem mass
      spectrometry.
AB  - Ibuprofen is widely used in human and veterinary medicine for the treatment of
      chronic pain as well as rheumatic and musculoskeletal disorders. However, the
      analgesic and anti-inflammatory properties of Ibuprofen have contributed to
      frequent drug abuse in equestrian sports. A sensitive and rapid gas
      chromatography with tandem mass spectrometry based method with a simple liquid
      liquid extraction and derivatization requiring 200 MUL volume of sample and 2 mL
      of extraction solvent for the simultaneous determination of ibuprofen and its
      metabolites was developed. The proposed procedure was optimized and validated
      according to the principles for bioanalytical methods. The assay achieved
      satisfactory validation parameters, namely, recovery (92.2-105%), interday
      accuracy (92.5-106%), and precision (0.3-4.4%) for all investigated compounds as
      well as limits of quantification of 50 ng/mL for ibuprofen, 2-hydroxyibuprofen,
      and carboxyibuprofen, 25 ng/mL for 1-hydroxyibuprofen and 100 ng/mL for 3
      hydroxyibuprofen. The applicability of the method was evaluated by the analysis
      of five real urine samples collected from different horses after drug
      administration. In view of the low limits of quantification, high selectivity,
      repeatability, and recovery, the procedure can be utilized for laboratory
      applications, including the control of ibuprofen abuse in equestrian sports for
      anti-doping purposes and drug/pharmaceutical mentality investigations.

PMID- 30101518
TI  - Pronounced antiepileptic activity of the subtype-selective GABAA -positive
      allosteric modulator PF-06372865 in the GAERS absence epilepsy model.
AB  - AIM: Antiepileptic drugs that modulate GABA have the potential to aggravate or
      improve the symptoms of absence epilepsy. PF-06372865 is a positive allosteric
      modulator (PAM) of alpha2/3/5 subunit-containing GABAA receptors with minimal
      activity at alpha1-containing receptors, which are believed to mediate many of
      the adverse events associated with benzodiazepines. The aim of this study was to
      assess the antiepileptic effect of PF-06372865 in a preclinical model of absence
      seizures. METHODS: Genetic absence epilepsy rats from Strasbourg (GAERS) was
      implanted with four cortical electrodes over the frontoparietal cortex, and the
      number and cumulated duration of spike-and-wave discharges (SWDs) were recorded
      for 10-90 minutes following administration of vehicle, PF-06372865, and positive
      controls diazepam and valproate. RESULTS: PF-06372865 (0.3, 1, 2, 10 mg kg-1 )
      dose-dependently reduced the expression of SWDs, including full suppression at
      the highest doses by 30 minutes after administration. CONCLUSIONS: PF-06372865
      demonstrated robust efficacy in suppressing SWDs in the GAERS model of absence
      epilepsy. To our knowledge, this is the first demonstration of antiepileptic
      activity of an alpha2/3/5-subtype-selective GABAA PAM in a model of absence
      epilepsy. Further study of the antiepileptic properties of PF-06372865 is
      warranted in patients with absence seizures.

PMID- 30101520
TI  - A novel patient-oriented numerical procedure for glaucoma drainage devices.
AB  - The present work analyses the performance of four glaucoma drainage devices, by
      means of a novel patient-oriented numerical procedure. The procedure is based on
      the three-dimensional geometry reconstruction from the stacks of tomographic
      images of a human eye, at different angles, on meshing and on thermo-fluid
      dynamics modelling activities, carried out on the reconstructed computational
      domain. The current three-dimensional eye model considers anterior chamber (AC),
      trabecular meshwork, Schlemm's canal, and collector channels, making use of
      generalised porous medium approach for modelling ocular porous tissue and
      cavities. The intraocular pressure (IOP) management inside AC of human eye is
      analysed, by comparing the results obtained for four drainage devices implanted
      in a human eye for glaucoma treatment, ie, ExPRESS shunt, iStent inject, SOLX
      gold micro shunt, and the novel silicon shunt device. The numerical results allow
      predicting the effects of the installation of these implants on human eyes, in
      terms of IOP decrease, aqueous humour velocity, pressure, friction coefficient,
      and local Nusselt number, pointing out the clear distinction between pre
      operative and post-operative eye conditions for different glaucoma surgical
      techniques.

PMID- 30101519
TI  - Laser treatments in early wound healing improve scar appearance: a randomized
      split-wound trial with nonablative fractional laser exposures vs. untreated
      controls.
AB  - BACKGROUND: In recent years, various lasers have increasingly been applied during
      wound healing to minimize scar formation. However, no consensus regarding
      treatment procedures exists. OBJECTIVES: To assess scar formation clinically
      after three nonablative fractional laser (NAFL) exposures, targeting the
      inflammation, proliferation and remodelling wound healing phases in patients vs.
      untreated controls. METHODS: A randomized controlled trial was performed using a
      split-wound design to assess excisional wound halves treated with 1540-nm NAFL
      vs. no laser treatment. Three NAFL exposures were provided: immediately before
      surgery, at suture removal and 6 weeks after surgery. NAFL exposures were applied
      using two handpieces, sequentially distributing energy deeply and more
      superficially in the skin (40-50 mJ per microbeam). Evaluated at 3 months of
      follow-up, the primary outcome was blinded, on-site evaluation using the Patient
      Observer Scar Assessment Scale (POSAS total; range from 6, normal skin to 60,
      worst imaginable scar). Secondary outcomes comprised blinded evaluation on the
      Vancouver Scar Scale (VSS) and standardized assessment comparing scar sides,
      carried out by blinded on-site, photo and patient assessments. This trial was
      registered with ClinicalTrials.gov (NCT03253484). RESULTS: Thirty of 32 patients
      completed the trial. At the 3-month follow-up, the NAFL-treated scar halves
      showed improvement compared with the untreated control halves on POSAS total:
      NAFL treated, median 11, interquartile range (IQR) 9-12 vs. control, median 12,
      IQR 10-16; P = 0.001. The POSAS subitems showed that the NAFL-treated halves were
      significantly less red and more pliable, and presented with smoother relief than
      the untreated controls. VSS total correspondingly revealed enhanced appearance in
      the NAFL-treated halves: median 2, IQR 1-2.5 vs. control, median 2, IQR 1.75-3, P
      = 0.007. The standardized assessment comparing appearance of scar halves
      demonstrated a low degree of correspondence between on-site, photo and patient
      assessments. NAFL-treated scars were rated as superior to untreated scars by 21
      of 29 patients. CONCLUSIONS: NAFL-treated scars showed subtle improvement
      compared with untreated control scars.

PMID- 30101522
TI  - Different dermoscopic features of clonal seborrhoeic keratoses.

PMID- 30101521
TI  - An epidemiological study of dental caries and associated factors among children
      residing in orphanages in Kerala, India: Health in Orphanages Project (HOPe).
AB  - BACKGROUND: It is estimated that, as of 2010, there were 32 million orphaned
      children in India. There is little published information on the oral health of
      children in orphanages in India. AIM: To determine caries status and associated
      risk factors among children in orphanages in Kerala, India. METHODS: This cross
      sectional study assessed caries using World Health Organization (WHO) criteria,
      and caries experience was reported as decayed, missing and filled primary or
      secondary teeth (dmft or DMFT, respectively). A brief questionnaire captured
      information on child oral health behaviours. Mean [standard deviation (SD)] and
      median [interquartile range (IQR)] scores were used to describe caries rates.
      Multivariable logistic regression analysis was conducted to identify independent
      disease predictors. Study design complexities, such as clustering by orphanage
      and stratification by district, were accounted for in the multivariable
      regression analysis. This was carried out using the survey commands in STATA 13.
      A value of P<0.05 was considered as statistically significant. RESULTS: Overall,
      1,137 children residing in 31 orphanages across the State of Kerala were
      recruited to the study. Female children made up 82% of the sample. In 6-year-old
      children the prevalence of caries was 77% and the mean dmft score was 3.60 (SD=
      3.50); in 12-year-old children the prevalence of caries was 44% and the mean DMFT
      score was 1.35 (SD = 1.96). Among 12-year-old children, those who reported being
      shown how to clean their teeth were less likely to have caries (odds ratio =
      0.62; 95% confidence interval: 0.38-0.95). CONCLUSION: Caries rates among
      children in orphanages were much higher than among children in the general
      population in Kerala. There is an urgent need for evidence-based and sustainable
      primary prevention strategies to reduce the burden of caries in this highly
      vulnerable population.

PMID- 30101523
TI  - Measurement of cytokines and chemokines and association with clinical severity of
      dermatomyositis and clinically amyopathic dermatomyositis.
AB  - BACKGROUND: Dermatomyositis (DM) is an autoimmune disease affecting primarily the
      skin, muscle and lung. Dysregulations of cytokines and chemokines are commonly
      found in inflammatory disorders. OBJECTIVES: To investigate the association
      between serum cytokines and chemokines and clinical severity, especially
      cutaneous lesions and interstitial lung disease (ILD) in patients with DM and
      clinically amyopathic DM (CADM). METHODS: Clinical features, laboratory findings
      and serum of 40 patients with DM or CADM were collected and analysed. Serum
      cytokines and chemokines were measured by enzyme-linked immunosorbent assay or
      cytometric bead array. A multiple unpaired t-test was performed to compare
      cytokines and chemokines in patients with DM and healthy controls. Correlations
      of serum cytokines and chemokines with disease severity were evaluated by
      Spearman's rank correlation test. RESULTS: Serum interferon (IFN)-beta [rs  =
      0.37, 95% confidence interval (CI) 0.078-0.62; P = 0.019] and CXCL10 (rs  = 0.32,
      95% CI to -0.004 to 0.57; P = 0.045) were significantly correlated with the
      Cutaneous Dermatomyositis Disease Area and Severity Index activity score in the
      subset of patients with DM or CADM. Serum levels of interleukin (IL)-6, IL-10, IL
      18 and IFN-beta were significantly higher in the patients with acute/subacute
      interstitial pneumonia (A/SIP) than in the subset without A/SIP (P < 0.05). IL-6
      (rs  = 0.54, 95% CI 0.27-0.72; P < 0.001) and IL-18 (rs  = 0.46, 95% CI 0.21
      0.65; P = 0.003) were significantly correlated with the serum level of anti
      melanoma differentiation-associated protein 5 antibody. CONCLUSIONS: Serum levels
      of IFN-beta and CXCL10 may be useful biomarkers for assessing cutaneous disease
      activity in patients with DM and CADM. In addition, serum IL-6, IL-10, IL-18 and
      IFN-beta were highly correlated with the occurrence of A/SIP. These cytokines may
      play a role in the pathogenesis of DM and CADM.

PMID- 30101524
TI  - Evaluating an owner-to-worker training intervention in California nail salons
      using personal air monitoring.
AB  - BACKGROUND: Chemicals in nail products have been linked to numerous health
      concerns. METHODS: We recruited Vietnamese-American nail salon owners and workers
      in California and randomized salons into an intervention or control group. Owners
      in the intervention group received training and then provided education to
      workers in their salons on best practices to reduce workplace chemical exposures.
      Methyl methacrylate (MMA), toluene, and total volatile organic compounds (TVOCs)
      were measured using personal air monitors worn by workers during the work-shift.
      RESULTS: We enrolled 77 salons (37 intervention and 40 control) and 200 workers.
      There was no significant intervention effect between the two groups. However, MMA
      and TVOCs were higher for workers who used gel polish and acrylic nails as well
      as in busy salons. CONCLUSIONS: Although the intervention did not show reductions
      in chemical levels, identifying worker tasks and salon characteristics that
      predict chemical levels can inform future interventions to reduce exposures.

PMID- 30101525
TI  - Targeting PDGF-mediated recruitment of pericytes blocks vascular mimicry and
      tumor growth.
AB  - Aggressive tumor cells can adopt an endothelial cell-like phenotype and
      contribute to the formation of a tumor vasculature, independent of tumor
      angiogenesis. This adoptive mechanism is referred to as vascular mimicry and it
      is associated with poor survival in cancer patients. To what extent tumor cells
      capable of vascular mimicry phenocopy the angiogenic cascade is still poorly
      explored. Here, we identify pericytes as important players in vascular mimicry.
      We found that pericytes are recruited by vascular mimicry-positive tumor cells in
      order to facilitate sprouting and to provide structural support of the vascular
      like networks. The pericyte recruitment is mediated through platelet-derived
      growth factor (PDGF)-B. Consequently, preventing PDGF-B signaling by blocking the
      PDGF receptors with either the small tyrosine kinase inhibitor imatinib or
      blocking antibodies inhibits vascular mimicry and tumor growth. Collectively, the
      current study identifies an important role for pericytes in the formation of
      vascular-like structures by tumor cells. Moreover, the mechanism that controls
      the pericyte recruitment provides therapeutic opportunities for patients with
      aggressive vascular mimicry-positive cancer types. (c) 2018 The Authors. The
      Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological
      Society of Great Britain and Ireland.

PMID- 30101526
TI  - Systematic review and meta-analysis of diagnosing gestational diabetes mellitus
      with one-step or two-step approaches and associations with adverse pregnancy
      outcomes.
AB  - BACKGROUND: There is an ongoing discussion about the optimal diagnostic strategy
      for gestational diabetes mellitus (GDM). OBJECTIVE: To assess the magnitude of
      the association between GDM diagnosed with the one-step (International
      Association of Diabetes and Pregnancy Study Groups criteria) or two-step
      (Carpenter and Coustan criteria) approach and selected adverse pregnancy
      outcomes. SEARCH STRATEGY: Five electronic databases were searched up to October
      2017 using Medical Subject Headings for each adverse outcome combined with the
      term "gestational diabetes." SELECTION CRITERIA: Observational studies assessing
      the one-step versus the two-step diagnostic approach in GDM. DATA COLLECTION AND
      ANALYSIS: Relative risks were extracted and random-effects models were used to
      estimate pooled relative risks (RRs). MAIN RESULTS: A total of 41 663
      participants from nine studies were included. Gestational diabetes mellitus was
      significantly associated with pre-eclampsia (RR 1.68 vs RR 1.77), cesarean
      delivery (RR 1.28 vs RR 1.33), and large for gestational age (RR 1.44 vs RR 1.68)
      when diagnosed with the one-step versus the two-step approach. A one-step
      diagnosis also increased the risks of neonatal intensive care unit admission and
      gestational hypertension, whereas a two-step diagnosis increased the incidence of
      macrosomia. CONCLUSIONS: Women with GDM diagnosed with either the one-step or the
      two-step approach were at increased risk for selected adverse pregnancy outcomes.
      The associations with the two-step method were slightly stronger.

PMID- 30101527
TI  - The healthcare burden of bradyarrhythmias and their impact on the outcomes of 11
      553 lipidoses-related hospitalizations: A nationwide inpatient contemplation.

PMID- 30101528
TI  - Overcoming resistance in non-small-cell lung cancer: A practical lesson for the
      medicinal chemist.
AB  - The introduction of tyrosine kinase inhibitors (TKIs) in the clinical management
      of oncological patients spread the light on the use of selective, rationally
      designed small molecules for the treatment of cancer. First-generation TKIs bared
      high response against these malignancies, although the unavoidable shadow of
      resistance limits their long-term efficacy. Non-small-cell lung cancer (NSCLC)
      accounts for 85% of lung cancer cases, and it is the first cause of cancer deaths
      worldwide for men and women. Traditional chemotherapy is marginally effective
      against this form, and erlotinib and gefitinib were introduced as first-line
      treatments based on the observation that the epidermal growth factor receptor
      (EGFR), a receptor tyrosine kinase (RTK), is mutated in several cases and, thus,
      represents a druggable target. EGFR-mutant and anaplastic lymphoma kinase (ALK)
      positive patients are more responsive to these treatments, even if secondary
      mutations causing resistance soon emerged. The efforts of medicinal chemists are
      currently oriented toward the development of new generations of TKIs overcoming
      these obstacles. We here overview the novel strategies from the point of view of
      the medicinal chemist: the rational structure-based drug design that led to the
      development of irreversible and non-ATP-competitive inhibitors. Such improvements
      parallel the novel therapeutic strategies adopted in the clinic, which are also
      discussed.

PMID- 30101529
TI  - Re-evaluating the Utility of Stress Ulcer Prophylaxis in the Critically Ill
      Patient: A Clinical Scenario-Based Meta-Analysis.
AB  - STUDY OBJECTIVE: Because recent studies have challenged the efficacy of stress
      ulcer prophylaxis (SUP) in the critically ill patient, our objective was to
      evaluate the efficacy of SUP with proton pump inhibitors (PPIs) or histamine2 
      receptor antagonists (H2 RAs) against placebo, control, no therapy, or enteral
      nutrition alone in critically ill adults. DESIGN: Meta-analysis with trial
      sequential analysis (TSA) of 34 randomized controlled trials. PATIENTS: A total
      of 3220 critically ill adults who received PPIs or H2 RAs versus placebo,
      control, no therapy, or enteral nutrition. MEASUREMENTS AND MAIN RESULTS: A
      systematic review was performed using a random effects meta-analysis with TSA
      according to a predefined protocol. Randomized controlled trials comparing PPIs
      or H2 RAs with either placebo, control, no therapy, or enteral nutrition alone
      were identified through a comprehensive search of the literature. Two blinded
      reviewers independently assessed studies for inclusion, risk of bias, and
      extracted data using Cochrane Collaborative methodology. The predefined primary
      outcomes were clinically important, overt, and any (clinically important plus
      overt) gastrointestinal bleeding. Secondary outcomes included pneumonia,
      Clostridium difficile-associated diarrhea (CDAD), and mortality. Subgroup
      analyses were conducted for the primary outcome by PPI or H2 RA use, intensive
      care unit (ICU) subtype, studies published after early goal-directed therapy
      (EGDT), the presence of risk factors for stress ulceration, and enteral nutrition
      use. Of the 34 trials included, 33 were judged as high risk of bias and 1 was
      judged as low risk. Use of SUP significantly reduced clinically important
      bleeding (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.37-0.76, p<0.001;
      I2  = 0%), overt bleeding (RR 0.55, 95% CI 0.39-0.76, p=0.0003; I2  = 53%), and
      any bleeding (RR 0.54, 95% CI 0.41-0.71, p<0.00001; I2  = 58%). TSA confirmed
      these findings. No significant differences in pneumonia, CDAD, or mortality were
      noted. Subgroup analyses revealed significant reductions in clinically important
      bleeding with SUP in neurosurgical patients (RR 0.37, p<0.05) but not in
      surgery/trauma or medical ICU patients with risk factors. SUP provided no benefit
      in studies published after EGDT. SUP significantly reduced clinically important
      bleeding regardless of the use of enteral nutrition (p<0.05). CONCLUSION: This
      meta-analysis demonstrated that SUP use was associated with significant
      reductions in bleeding but not mortality. SUP should not be abandoned until large
      randomized trials demonstrate the futility of this intervention.

PMID- 30101530
TI  - Doping: A Key Enabler for Organic Transistors.
AB  - Organic field-effect transistors (OFETs) are the central building blocks of
      organic electronics, but still suffer from low performance and manufacturing
      difficulties. This is due in part to the absence of doping, which is mostly
      excluded from OFET applications for the concern about uncontrollable dopant
      diffusion. Doping enabled the modern semiconductor industry to build essential
      components like Ohmic contacts and P-N junctions, empowering devices to function
      as designed. Recent breakthroughs in organic semiconductors and doping techniques
      demonstrated that doping can also be a key enabler for high-performance OFETs.
      However, the knowledge of organic doping remains limited particularly for OFET
      use. Therefore, this review addresses OFET doping from a device perspective. The
      paper overviews doping basics and roles in advanced complementary technologies.
      These fundamentals help to understand why and how doping provides the desired
      transistor characteristics. Typical OFETs without doping are discussed, with
      consideration for operating principle and problems caused by the absence of
      doping. Achievements for channel, contact, and overall doping are also examined
      to clarify the corresponding doping roles. Finally, doping mechanisms,
      techniques, and dopants associated with OFET applications are reviewed. This
      paper promotes fundamental understanding of OFET doping for the development of
      high-performance OFETs with doped components.

PMID- 30101531
TI  - Acne: a side-effect of masculinizing hormonal therapy in transgender patients.
AB  - BACKGROUND: Masculinizing hormonal treatment in transgender men has the potential
      to increase the level of androgens at end organs, including the pilosebaceous
      unit. Androgen-induced sebocyte growth and differentiation, sebum production and
      infundibular keratinization may underlie the development of acne vulgaris among
      patients receiving this therapy. OBJECTIVES: The aim of this article is to
      familiarize dermatologists with the sensitivities and challenges of treating acne
      in transgender male individuals. METHODS: This review article discusses the
      pathogenesis and treatment of acne in transgender men on testosterone therapy and
      highlights the unique considerations in treating this underserved patient
      population. RESULTS: Despite the incidence of treatment-related acne and the
      unique considerations in treating transgender men, studies addressing this topic
      among this patient population are limited. CONCLUSIONS: Generally, the standard
      guidelines for the treatment of acne can be followed in treating these patients;
      however, several medical, social and psychological factors should be considered.

PMID- 30101532
TI  - Taurine abrogates mammary carcinogenesis through induction of apoptosis in
      Sprague-Dawley rats.
AB  - Breast cancer is one of the most severe problems in oncology. Taurine is a sulfur
      containing amino acid with vital biological functions. The current study was
      intended to investigate the abnormalities in the expression of apoptosis
      associated proteins that lead to the progression of 7,12-dimethyl
      benz[a]anthracene (DMBA)-induced breast cancer and to expose the protective
      effect of taurine on it. Rats were induced with DMBA by gastric intubation to
      induce breast cancer. Breast cancer-bearing animals were posttreated with
      taurine. The breast tumors induced by DMBA, analyzed in the current study, were
      characterized by increased protein/DNA expression of Bcl-2 associated with
      downregulation in the expression of p53, Bax, and caspases. Taurine treatment
      reverted all the above changes induced by DMBA and inhibited the development of
      rat breast carcinoma through its ability to induce apoptosis.

PMID- 30101533
TI  - Comparison of maternal and perinatal outcomes in women with super obesity based
      on planned mode of delivery.
AB  - BACKGROUND: Currently, little evidence exists to guide mode of delivery in
      pregnant women with super obesity. There is a trend toward elective caesarean
      delivery in this population with little evidence of improved maternal or neonatal
      outcomes. AIM: Our study compares maternal and neonatal outcomes based on planned
      mode of delivery and aimed to identify predictors for a successful vaginal
      delivery. MATERIALS AND METHODS: This retrospective observational study explored
      maternal and neonatal outcomes of women with a body mass index >=50 who birthed
      following a singleton pregnancy at >=36 weeks gestation over a 10 year period at
      a single centre in Melbourne, Australia. Outcomes between women having a planned
      vaginal or planned caesarean birth were compared on an intention-to-treat basis,
      with logistic regression used to determine factors predictive of a vaginal birth.
      RESULTS: A total of 275 women with super obesity were identified. One hundred and
      ninety-nine (72%) planned a vaginal birth, which was successful for 70%. Planned
      vaginal birth was associated with lower rates of postpartum complications
      requiring readmission (5% vs 16%; P = 0.003). Neonatal resuscitation requirements
      and Apgar scores at five minutes were similar between groups. Multiparity was the
      strongest predictor of a successful vaginal birth while medical intervention in
      labour was associated with a reduced rate of success in primiparous women.
      CONCLUSIONS: Contrary to current trends in practice, a trial of labour for women
      with super obesity, when facilities and skills permit, appears a safe option for
      mother and baby.

PMID- 30101534
TI  - Sensory mechanisms of natal stream imprinting and homing in Oncorhynchus spp.
AB  - Juvenile Oncorhynchus spp. can memorise their natal stream during downstream
      migration; juveniles migrate to feed during their growth phase and then they
      migrate long distances from their feeding habitat to their natal stream to
      reproduce as adults. Two different sensory mechanisms, olfaction and navigation,
      are involved in the imprinting and homing processes during short-distance
      migration within the natal stream and long-distance migration in open water,
      respectively. Here, olfactory functions are reviewed from both neurophysiological
      studies on the olfactory discrimination ability of natal stream odours and
      neuroendocrinological studies on the hormonal controlling mechanisms of olfactory
      memory formation and retrieval in the brain. These studies revealed that the long
      term stability of dissolved free amino-acid composition in the natal stream is
      crucial for olfactory imprinting and homing. Additionally, the brain-pituitary
      thyroid and brain-pituitary-gonadal hormones play important roles in olfactory
      memory formation and retrieval, respectively. Navigation functions were reviewed
      from physiological biotelemetry techniques with sensory interference experiments
      during the homing migration of anadromous and lacustrine Oncorhynchus spp. The
      experiments demonstrated that Oncorhynchus spp. used compass navigation
      mechanisms in the open water. These findings are discussed in relation to the
      sensory mechanisms involved in natal stream imprinting and homing in Oncorhynchus
      spp.

PMID- 30101535
TI  - Put the Sun in the Tank: Future Developments in Sustainable Energy Systems.
AB  - The conversion of energy systems toward sustainable solutions has been
      progressing for several years. The effect on protecting the climate can now be
      estimated through new projections and is presented here for the European Union.
      The results are compared to the goals of the Paris Climate Agreement and show
      that additional, new and qualitative measures must be taken.

PMID- 30101536
TI  - Peripheral Th17 cells expressing beta7 intestinal homing receptor in recent and
      chronic HIV infections.
AB  - The objective of this study was to conduct an analysis of peripheral blood Th17
      cells with the ability to home to gut mucosa (CD4+ Th17+ beta7+ ) during recent
      or chronic human immunodeficiency virus (HIV) infections. The relationship
      between HIV load and systemic inflammation markers was studied. Twenty-five
      patients with recent (n = 10) or chronic (n = 15) untreated HIV infections; 30
      treated HIV-infected patients with undetectable HIV load at the time of inclusion
      and 30 healthy controls were included. Bacterial translocation markers (16S
      rDNA), soluble CD14 (sCD14) and interleukin (IL)-6 monocyte activation
      parameters, CD4/CD8 ratio and T helper type 17 (Th17) subpopulations [CD4+ Th17+
      expressing the IL-23 receptor (IL-23R) or beta7] were analysed at baseline and
      after 6 and 12 months of anti-retroviral therapy (ART). 16S rDNA was detected in
      all patients. Significantly increased serum levels of sCD14 and IL-6 and a
      decreased CD4/CD8 ratio were observed in patients. Similar percentages of CD4+ IL
      23R+ and CD4+ Th17+ beta7+ cells were observed in healthy controls and patients
      at baseline. After 12 months of therapy, patients with a recent HIV infection
      showed significant increases of CD4+ IL-23R+ and CD4+ Th17+ beta7+ cell
      percentages and a decrease in IL-6 levels, although 16S rDNA continued to be
      detectable in all patients. No significant differences were observed in Th17
      subpopulations in patients with chronic HIV infection after therapy. Early
      initiation of ART helps to increase the number of Th17 cells with the ability to
      home to the intestinal mucosa and to partially restore gut mucosal homeostasis.
      These results provide a rationale for initiating ART during the acute phase of
      HIV infection.

PMID- 30101537
TI  - Neuraminidase-mediated desialylation augments AAV9-mediated gene expression in
      skeletal muscle.
AB  - BACKGROUND: Following systemic delivery, AAV9-mediated gene expression is
      significantly increased in ischemic versus non-ischemic muscle, suggesting that
      AAV9 is an attractive vector for treating peripheral arterial disease. Potential
      mechanisms underlying ischemia-augmented expression include: (i) increased
      vascular permeability and (ii) "unmasking" of endogenous AAV9 receptors. In the
      present study, we aimed to reconstitute the ischemic induction of AAV9 in vivo,
      using local injection of histamine (to increase vascular permeability) and
      neuraminidase (to desialylate cell surface glycans). METHODS: Bioassays were
      performed to optimize the effects of histamine and neuraminidase after
      intramuscular injection. Histamine and/or neuraminidase were then injected
      intramuscularly shortly before intravenous injection of an AAV9 vector expressing
      luciferase. Luciferase expression was serially assessed with bioluminescence
      imaging. At the end of the study, tissues were harvested for assays of luciferase
      activity and AAV9 genome copy number aiming to assess AAV-mediated gene
      expression and transduction, respectively. RESULTS: Intramuscular injection of
      either neuraminidase or neuraminidase plus histamine significantly increased both
      transduction and gene expression, whereas histamine alone had little effect. Pre
      injection with neuraminidase increased AAV9-mediated gene delivery by four- to
      nine-fold and luciferase activity by 60-100-fold. Luciferase activity in
      neuraminidase-injected muscle was > 100-fold higher than in any off-target tissue
      (including heart, liver and brain). CONCLUSIONS: The ischemic induction of AAV9
      mediated gene expression in muscle can largely be reconstituted by pre-injecting
      neuraminidase intranmuscularly. This strategy may prove useful in future human
      gene therapy protocols as a quick and efficient means to selectively target
      systemically injected AAV9 to localized regions of muscle, thus decreasing the
      potential for adverse effects in off-target tissues.

PMID- 30101538
TI  - The other side of the coin: Hypersociability.
AB  - Affiliative social motivation and behavior, that is, sociability that includes
      attachment, prosocial behavior (sharing, caring and helping) and empathy (the
      ability to understand and share the feelings of others), has high variability in
      the human population, with a portion of people outside of the normal range. While
      psychiatric disorders and autism spectrum disorders are typically associated with
      a deficit in social behavior, the opposite trait of hypersociability and
      indiscriminate friendliness are exhibited by individual with specific
      neurodevelopmental disorders and following early adverse care. Here we discuss
      both genetic and environmental factors that cause or increase the risk for
      developing pathological hypersociability from human to rodent models.

PMID- 30101540
TI  - Addressing Cancer Chemotherapeutic Toxicity, Resistance, and Heterogeneity: Novel
      Theranostic Use of DNA-Encoded Small Molecule Libraries.
AB  - Major problems in cancer chemotherapy are toxicity, resistance, and cancer
      heterogeneity. A new theranostic paradigm has been proposed by the authors. Many
      million small molecules (SM) are bound to the proteins extracted from a patient's
      cancer. SM that also bind proteins extracted from normal human tissues are
      subtracted from the cancer protein bound SM leaving a large array of SM targeting
      many sites on each of the cancer biomarkers. Targeting many more than the
      conventional 1 - 4 cancer biomarkers will reduce development of tumor resistance.
      After several cycles of selection and counter selection, DNA codes appended to
      the SM will be PCR amplified to provide templates for restricted libraries of the
      SM to improve selectivity and sensitivity. The large array of selected and
      counter selected SM assures that many of the compounds in the array will
      penetrate the cell membrane and bind to intracellular targets, low tumor
      resistance, low background for imaging, low therapeutic toxicity, and targeting
      of the diverse biomarkers present in the heterogeneous mixture of cells in
      primary and metastatic cancer. Theranostic use of radiolabeled SM binding many
      sites on many, not necessarily critical, biomarkers provides high cancer cell
      killing. Experiments to provide proof of principle of this novel concept
      suggested by the authors.

PMID- 30101539
TI  - Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir
      alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or
      efavirenz, FTC and TDF: 96-week results from two randomized clinical trials.
AB  - OBJECTIVES: The single-tablet regimen rilpivirine, emtricitabine and tenofovir
      alafenamide (RPV/FTC/TAF) for treatment of HIV-1-infected adults was approved
      based on bioequivalence. We assessed the clinical efficacy, safety and
      tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil
      fumarate (TDF) or efavirenz (EFV)/FTC/TDF. METHODS: We conducted two distinct
      randomized, double-blind, active-controlled, noninferiority trials in
      participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160). Each
      study randomized virologically suppressed (HIV-1 RNA < 50 copies/mL) adults (1:1)
      to switch to RPV/FTC/TAF or continue their current regimen for 96 weeks. We
      evaluated efficacy as the proportion with HIV-1 RNA < 50 copies/mL using the Food
      and Drug Administration snapshot algorithm and prespecified bone and renal
      endpoints at week 96. RESULTS: We randomized and treated 630 participants in
      Study 1216 (RPV/FTC/TAF, n = 316; RPV/FTC/TDF, n = 314) and 875 in Study 1160
      (RPV/FTC/TAF, n = 438; EFV/FTC/TDF, n = 437). In both studies, the efficacy of
      switching to RPV/FTC/TAF was noninferior to that of continuing baseline therapy
      at week 96, with respective percentages of patients with HIV RNA < 50 copies/mL
      being 89.2% versus 88.5% in Study 1216 [difference 0.7%; 95% confidence interval
      (CI) -4.3 to +5.8%] and 85.2% versus 85.1% in Study 1160 (difference 0%; 95% CI 
      4.8 to +4.8%). No participant on RPV/FTC/TAF developed treatment-emergent
      resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF. Compared with
      continuing baseline therapy, significant improvements in bone mineral density and
      renal tubular markers were observed in the RPV/FTC/TAF groups (P < 0.001).
      CONCLUSIONS: Switching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF was safe
      and effective and improved bone mineral density and renal biomarkers up to 96
      weeks with no cases of treatment-emergent resistance.

PMID- 30101541
TI  - Effects of live yeast (Saccharomyces cerevisiae) and type of cereal on rumen
      microbial fermentation in a dual flow continuous culture fermentation system.
AB  - Live yeast additives may help optimize ruminal fermentation of high-grain diets,
      especially when the starch of the ration is highly fermentable. Eight dual flow
      continuous culture fermenters were used in a 2 * 2 factorial design in two
      replicated periods of 9 days (six for adaptation and three for sampling) to
      determine the effect of live yeast and type of cereal on rumen microbial
      fermentation and nutrient digestibility. Main factors were the addition of live
      yeast: no yeast (NY) vs. 2 * 107 CFU of yeast/g of diet (LY); and type of cereal
      in the diet: corn (CO) vs. barley (BA). All fermenters were fed 80 g dry
      matter/day of a 10-90 forage to concentrate diet and pH was allowed to fluctuate
      with an upper (6.6) and lower (5.5) limit. Treatment BA increased OM digestion,
      valerate proportion, peptides and ammonia N fractions, ammonia N flow, crude
      protein degradation and target copies of Megasphaera elsdenii; and decreased NDF
      digestion, propionate proportion, branched-chain VFA (BCVFA) concentration, AA-N
      fraction and nonammonia N flow. Treatment LY increased BCVFA and decreased
      ammonia N fraction and flow, and the target copies of Streptococcus bovis.
      Treatment LY decreased the slope of pH drop, the area under pH 6.0 and the gas
      production. These results suggest potential benefits of LY in stabilizing the
      fermentation of BA-based diets.

PMID- 30101543
TI  - Homogeneous Catalysis from Young Investigators in Asia.
AB  - Contemporary Science! Homogeneous catalysis plays a significant role in
      fundamental research and industry. After decades of development, it is still
      steadily growing: higher catalytic efficiency and selectivity, deeper mechanistic
      understanding, and more applications continue to emerge. The past few years have
      seen the rise of young chemists in this field from Asia. This special issue
      honors their contribution in the field of homogeneous catalysis.

PMID- 30101542
TI  - Structural and Mutagenesis Studies of the Thiamine-Dependent, Ketone-Accepting
      YerE from Pseudomonas protegens.
AB  - A wide range of thiamine diphosphate (ThDP)-dependent enzymes catalyze the
      benzoin-type carboligation of pyruvate with aldehydes. A few ThDP-dependent
      enzymes, such as YerE from Yersinia pseudotuberculosis (YpYerE), are known to
      accept ketones as acceptor substrates. Catalysis by YpYerE gives access to chiral
      tertiary alcohols, a group of products difficult to obtain in an enantioenriched
      form by other means. Hence, knowledge of the three-dimensional structure of the
      enzyme is crucial to identify structure-activity relationships. However, YpYerE
      has yet to be crystallized, despite several attempts. Herein, we show that a
      homologue of YpYerE, namely, PpYerE from Pseudomonas protegens (59 % amino acid
      identity), displays similar catalytic activity: benzaldehyde and its derivatives
      as well as ketones are converted into chiral 2-hydroxy ketones by using pyruvate
      as a donor. To enable comparison of aldehyde- and ketone-accepting enzymes and to
      guide site-directed mutagenesis studies, PpYerE was crystallized and its
      structure was determined to a resolution of 1.55 A.

PMID- 30101544
TI  - Incidence of aspiration in infants with single-ventricle physiology following
      hybrid procedure.
AB  - BACKGROUND: Swallowing dysfunction is a known complication for infants with
      complex congenital heart disease (CHD), but few studies have examined swallowing
      outcomes following the hybrid procedure for stage 1 palliation in children with
      single ventricle physiology. OBJECTIVES: (1) Identify the incidence of aspiration
      in all infants with single ventricle physiology who underwent the hybrid
      procedure and (2) Compare results of clinical bedside and instrumental swallowing
      evaluations to examine the predictive value of a less invasive swallowing
      assessment for this population of high-risk infants. METHODS: This was a
      retrospective cohort chart review study. All patients with single-ventricle
      physiology who underwent the hybrid procedure received a referral for subsequent
      instrumental swallow assessment during a 4-year period. Results from clinical
      bedside evaluations were compared to those of the instrumental assessment.
      RESULTS: Fifty infants were included in this study. During instrumental swallow
      assessment, aspiration was observed in 28% of infants following the hybrid
      procedure. Normal swallowing function was identified in 44% of infants, and 28%
      demonstrated laryngeal penetration. Neither length of intubation nor prematurity
      were found to be predictors of aspiration. Thirty-six of these infants were
      assessed via clinical bedside evaluation prior to the instrumental evaluation.
      The sensitivity of the clinical bedside evaluation was 0.73 and the specificity
      was 0.92. CONCLUSIONS: This study reports on a cohort of infants with single
      ventricle physiology following the hybrid procedure and found the incidence of
      aspiration to be lower than previously reported. Improved clinical bedside
      evaluation guidelines are needed so that clinicians can predict more reliably
      which infants are at risk for aspiration following the hybrid procedure.

PMID- 30101546
TI  - Successful Management of Gorham-Stout Disease in Scapula and Ribs: A Case Report
      and Literature Review.
AB  - Gorham-Stout disease (GSD) is an extremely rare bone condition of unknown
      etiology characterized by spontaneous and progressive resorption of bones. GSD
      can occur at any age and is not related to gender, genetic inheritance, or race.
      Any part of the skeleton can be affected and the symptoms correlate with the
      sites involved. The diagnosis of GSD is established based on the combination of
      clinical, radiologic, and histologic features after excluding other diseases.
      Because of its rarity, current knowledge is limited to case reports and there is
      no agreement on the best strategy for treatment. The following case report
      describes a successfully treated case of GSD in a 26-year-old male patient with
      the left scapula and the 7th-9th left ribs involved. The patient was diagnosed
      with osteoporosis-related pleural effusion at a local hospital. In our
      institution, the patient was diagnosed with GSD and treated with radiotherapy and
      bisphosphonate. The disease was controlled and there was no evidence of disease
      progression during follow-up. Genetic sequencing was performed to investigate the
      etiology of GSD. In addition, the present study reviews the theories regarding
      the etiology, the clinical manifestations, the diagnostic approaches, and
      treatment options for this rare disease.

PMID- 30101545
TI  - Serum uric acid could be served as an independent marker for increased risk and
      severity of ascending aortic dilatation in Behcet's disease patients.
AB  - OBJECTIVE: This study aimed to investigate the correlation of serum uric acid
      (SUA) with risk and dilatation diameter of ascending aortic dilatation (AAD) in
      Behcet's disease (BD) patients. METHODS: Seventeen BD patients complicated with
      AAD and 20 BD patients without AAD were consecutively enrolled and categorized
      into AAD group and control group, respectively. Ascending aortic dilatation was
      determined by two-dimensional doppler echocardiographic examination, and AAD was
      defined as a diameter of ascending aorta >=3.8 and <4.4 cm. SUA was detected by
      quantitative immunoassay method. RESULTS: Ascending aortic dilatation patients
      presented with higher proportion of male patients (P = 0.003), hypertension
      occurrence (P = 0.036) and increased diameter of ascending aorta (P < 0.001)
      compared to controls. SUA was elevated in AAD patients compared to controls (P =
      0.002), and receiver operating characteristic curve displayed that SUA presented
      with great predictive value for AAD risk in BD patients with area under curve
      (AUC) 0.821 (95% CI 0.675-0.966). Pearson's analysis also disclosed that SUA was
      positively correlated with ascending aortic diameter in total BD patients.
      However, no difference of CRP (P = 0.219) or ESR (P = 0.320) between AAD patients
      and controls was observed, and no correlation of CRP (R = -0.150, P = 0.377) or
      ESR (R = 0.067, P = 0.692) with ascending aortic diameter in total BD patients
      was discovered either. Further multivariate logistic regression illuminated that
      SUA was an independent factor predicting AAD risk in BD patients (P = 0.031).
      CONCLUSIONS: Serum uric acid could be served as an independent marker for
      increased risk and severity of AAD in BD patients.

PMID- 30101548
TI  - Organic Light-Emitting Field-Effect Transistors: Device Geometries and
      Fabrication Techniques.
AB  - Organic light-emitting transistors (OLETs), as novel and attractive kinds of
      organic electronic devices, have gained extensive attention from both academia
      and industry. The unique device architectures can simultaneously combine the
      electrical switching functionality of organic field-effect transistors and the
      light generation capability of organic light-emitting diodes in a single device,
      thereby holding great promise for reducing the complicated processes of next
      generation pixel circuitry. This review involves the design, fabrication, and
      applications of OLETs with a comprehensive coverage of this field with the aim to
      give a deep insight into the intrinsic mechanisms of devices. Challenges and
      future prospects of OLETs are also discussed.

PMID- 30101547
TI  - Comprehensive insight into functional interaction between GNB3 C825T and eNOS T
      786C, G894T gene polymorphisms and association with susceptibility to diabetic
      erectile dysfunction.
AB  - BACKGROUND: No study has assessed the possible involvement of endothelial nitric
      oxide synthase (eNOS) T-786C and G894T and G-protein beta3 subunit (GNB3) C825T
      polymorphisms with susceptibility to diabetic vasculogenic erectile dysfunction
      (VED) in North African subjects. OBJECTIVES: Our aim was to evaluate the
      interaction and association between these gene polymorphisms and this disorder.
      MATERIALS AND METHODS: A total of 164 type 2 diabetes patients with VED diagnosed
      with penile color Doppler ultrasonography and 148 age-matched healthy volunteers
      were genotyped for the rs1799983 (G894T) and rs2070744 (T-786C) of the eNOS gene
      and the rs5443 (C825T) of the GNB3 gene using the PCR-RFLP method. RESULTS: A
      significant association of the eNOS G894T (p = 0.005) and T-786C (p = 0.02) with
      altered susceptibility to VED was observed. The risk also holds for the G894T and
      T-786C eNOS gene polymorphisms when excluding patients with dyslipidemia and
      cardiovascular diseases (p = 1.7.10-4 and p = 3.2.10-5 , respectively). The
      univariate odds ratio associated with CC alleles of the eNOS T-786C revealed a
      four times increased risk for VED (OR = 4.04; 95% CI = 1.53-10.67; p = 0.006).
      VED risk was also associated with the G894T variant under dominant model (p =
      0.002) and the T-786C variant under recessive model (p = 0.004). Furthermore, the
      concomitant presence of the combined genotypes of the 894T and 786T strongly
      affected the predisposition to VED (p = 0.007). DISCUSSION AND CONCLUSION: Our
      study gave a comprehensive insight into functional interaction between GNB3 and
      eNOS gene polymorphisms and suggests that the eNOS G894T and T-786C variants are
      strong predisposing factors of VED susceptibility within men with type 2
      diabetes.

PMID- 30101549
TI  - Insights into Crystal Facets of Perovskite SrSnO3 as High-Performance
      Photocatalysts toward Environmental Remediation.
AB  - To gain in-depth insights into the relevant exposed crystal planes for the
      photocatalytic performance of perovskite-structured oxides, SrSnO3 nanocrystals
      with different microstructures were synthesized and their photocatalytic activity
      for the degradation of simulated dye was investigated. The as-obtained
      orthorhombic SrSnO3 nanorods with exposed {001} crystal planes showed higher
      photocatalytic activity for decomposing methylene blue than that of SrSnO3
      nanoribbons with exposed {111} crystal planes. The surface atomic configurations
      revealed that the quantity of SnO2 overlayer on the {001} crystal facets is
      slightly greater than that on {111} crystal planes, which results in exposed
      {001} crystal facets of the SrSnO3 nanorods that can exhibit better activity in
      the photocatalytic process, due to fewer lattice defects, which act as traps for
      photogenerated charge carriers to decrease the recombination of photoexcited
      electrons and holes. This originated from narrowing of the crystal face distance
      and slight variation of the unit cell parameters; the crystallographic axis
      became shorter and the value of lattice strain became smaller. As a result,
      SrSnO3 nanocrystals exhibited different surface behavior under post-treatment
      conditions and exhibited variation in the photocatalytic properties. The findings
      reported herein highlight the importance of probing the properties of surface
      facets in the evaluation of the photocatalytic performance of ternary metal
      oxides.

PMID- 30101550
TI  - The emergence of porcine circovirus 2 infections in the Northeastern part of
      India: A retrospective study from 2011 to 2017.
AB  - Porcine circovirus (PCV) infection has emerged as an alarming threat to the pig
      population of India, especially in the Northeastern region (NER) over the last 10
      years. The present study is a comprehensive report of the seroepidemiology of
      PCV2 and its incidences in the pig population from organized and unorganized
      farms of the entire NER of India from 2011 to 2017. A total of 5697 serum samples
      were screened by ELISA and the mean positivity of PCV2 antibodies in suspected
      sera was 31.27%. A total of 22 confirmed cases of PCV2 infection were recorded
      during the years 2014-2017. Seroprevalence of PCV2 infection in sows causing
      reproductive disorders in NER suggested its higher incidence in organized farms
      (65.7%) as compared to unorganized farms (17.6%). A detailed pathological and
      histopathological examination of the tissue samples collected from the affected
      animals indicated the presence of PCV2. Molecular characterization and
      phylogenetic analysis of four PCV2 isolates depicted the circulation of PCV2d
      genotype in the states of Meghalaya and Assam.

PMID- 30101551
TI  - Impact of Concomitant Mitral Valve Surgery With LVAD Placement: Systematic Review
      and Meta-Analysis.
AB  - The aim of this systematic review and meta-analysis was to evaluate the outcomes
      of concomitant mitral valve surgery for significant preexisting mitral
      regurgitation (MR) in patients undergoing continuous-flow left ventricular assist
      device (CF-LVAD) implantation. Electronic search was performed to identify all
      studies in the English literature examining concurrent mitral valve surgery in
      patients with CF-LVAD implantation. Identified articles were systematically
      assessed for inclusion and exclusion criteria. Of 2319 studies identified, 8
      studies were included. Among 445 patients with moderate to severe or severe MR,
      113 (25.4%) patients received concurrent mitral valvular intervention during CF
      LVAD implantation. There were no significant differences in cardiopulmonary
      bypass time (MR Surgery 154 min vs. no MR Surgery 119 min, P = 0.64) or hospital
      length of stay (MR Surgery 21 days vs. no MR Surgery 18 days, P = 0.93). On
      follow-up, there were no significant differences in freedom from greater than
      moderate MR (MR Surgery 100% vs. no MR Surgery 74%, P = 0.12) or left ventricular
      end-diastolic diameter (MR Surgery: 60 mm vs. no MR Surgery 65 mm, P = 0.51).
      Survival was comparable at 6-months (MR Surgery 77% vs. no MR Surgery 81%, P =
      0.75), 1-year (MR Surgery 72% vs. no MR Surgery 80%, P = 0.36), and 2-years of
      follow-up (MR Surgery 65% vs. no MR Surgery 70%, P = 0.56). The results of our
      systematic review and meta-analysis of 8 studies consisting of 445 patients
      demonstrates that the addition of mitral valve intervention to CF-LVAD
      implantation appears to be safe with comparable survival to those undergoing CF
      LVAD implantation alone. Large prospective randomized clinical trials are needed
      to elucidate whether concomitant mitral valve intervention during CF-LVAD
      implantation in patients with severe MR is necessary.

PMID- 30101553
TI  - Comparison of healthcare resource utilization and costs in patients with type 2
      diabetes initiating dapagliflozin versus sitagliptin.
AB  - AIMS: To compare healthcare costs and utilization in patients with type 2
      diabetes (T2D) who initiated dapagliflozin (DAPA) with costs and utilization in
      those who initiated sitagliptin (SITA) in a real-world setting. MATERIALS AND
      METHODS: This was a retrospective study of health plan enrollees in two US
      commercial claims databases or Medicare Part D. The study population comprised
      adult patients with T2D who initiated DAPA or SITA between January 1, 2014 and
      April 30, 2015. DAPA and SITA initiators were propensity-score-matched, and
      healthcare utilization and costs during the 1-year follow-up period were
      compared. Analyses were conducted separately for patients with evidence of oral
      antidiabetic drug (OAD) monotherapy use at baseline. RESULTS: A total of 2722
      patients were included in each matched cohort. Follow-up unadjusted all-cause
      costs ($16 065 and $17 281; P = 0.135) and diabetes-related costs ($9697 and
      $9354; P = 0.539) were similar in the DAPA and SITA cohorts. Higher office and
      outpatient visit costs in the SITA group were offset by higher pharmacy costs in
      the DAPA group. In the subgroup of 1804 patients with OAD monotherapy use at
      baseline, patients in the SITA group had higher total all-cause costs compared
      with those in the DAPA group ($14 884 vs. $12 353; P = 0.026). CONCLUSION:
      Patients who initiated DAPA or SITA had similar all-cause and diabetes-related
      healthcare costs over 1 year of follow-up. In the subgroup of patients treated
      with OAD monotherapy at baseline (84% metformin monotherapy), those who initiated
      DAPA as add-on therapy had lower costs than patients who added SITA.

PMID- 30101552
TI  - Systematic review of the impact of point-of-care testing for influenza on the
      outcomes of patients with acute respiratory tract infection.
AB  - Acute respiratory tract infections are a major cause of morbidity and mortality
      and represent a significant burden on the health care system. Laboratory testing
      is required to definitively distinguish infecting influenza virus from other
      pathogens, resulting in prolonged emergency department (ED) visits and
      unnecessary antibiotic use. Recently available rapid point-of-care tests (POCT)
      may allow for appropriate use of antiviral and antibiotic treatments and decrease
      patient lengths of stay. We undertook a systematic review to assess the effect of
      POCT for influenza on three outcomes: (1) antiviral prescription, (2) antibiotic
      prescription, and (3) patient length of stay in the ED. The databases Medline and
      Embase were searched using MeSH terms and keywords for influenza, POCT,
      antivirals, antibiotics, and length of stay. Amongst 245 studies screened, 30
      were included. The majority of papers reporting on antiviral prescription found
      that a positive POCT result significantly increased use of antivirals for
      influenza compared with negative POCT results and standard supportive care. A
      positive POCT result also led to decreased antibiotic use. The results of studies
      assessing the effect of POCT on ED length of stay were not definitive. The
      studies assessed in this systematic review support the use of POCT for diagnosis
      of influenza in patients suffering an acute respiratory infection. Diagnosis
      using POCT may lead to more appropriate prescription of treatments for infectious
      agents. Further studies are needed to assess the effect of POCT on the length of
      stay in ED.

PMID- 30101554
TI  - Metabolomic signature of the postprandial experience.
AB  - BACKGROUND: Ingestion of a meal up to maximal tolerance induces unpleasant
      fullness sensation and changes in circulating metabolites. Our aim was to
      evaluate the relation between postprandial sensations and the metabolomic
      responses to a comfort meal. METHODS: In 32 non-obese healthy men, homeostatic
      sensations (hunger/satiety, fullness), hedonic sensations (digestive well-being,
      mood), and the metabolomic profile in plasma (low-molecular weight metabolites
      and lipoprotein profiles) were measured before and 20 minutes after a comfort
      meal (warm ham and cheese sandwich and juice; total 300 mL; 425 kcal). Perception
      was measured on 10 cm scales and the metabolomic response by nuclear magnetic
      resonance spectroscopy. KEY RESULTS: The comfort meal induced homeostatic
      sensations (satiety and fullness) associated with a positive hedonic reward
      (enhanced digestive well-being and mood) and a clear change in the metabolomic
      profile with a sharp discrimination between the pre and postprandial state by a
      non-supervised principal component analysis. The change in circulating
      metabolites correlated with the postprandial sensations: the increase in alanine
      correlated with the increase in fullness (R = 0.50; P = 0.004) and well-being (R
      = 0.50; P = 0.004); the increase in glucose correlated with the sensation of
      fullness (R = 0.40; P = 0.023) and enhanced mood (R = 0.41; P = 0.020).
      CONCLUSION AND INFERENCES: Metabolomic changes in the response to a meal may
      provide an objective index of the postprandial experience, which may have
      clinical implications in the management of patients with poor meal tolerance or
      meal-related symptoms.

PMID- 30101556
TI  - Lamotrigine pharmacokinetics following oral and stable-labeled intravenous
      administration in young and elderly adult epilepsy patients: Effect of age.
AB  - OBJECTIVE: The objectives of this study were to investigate the effect of age on
      pharmacokinetic parameters of lamotrigine (LTG) and estimate parameter
      variability. METHODS: Patients (>18 years old) who were already on a steady-state
      dose of LTG therapy with no interacting comedications were enrolled. Patients
      with significant cardiac disease, severe kidney dysfunction, or moderate-to
      severe liver dysfunction were excluded. Fifty milligrams of a stable-labeled
      intravenous LTG formulation (SL-LTG) replaced 50 mg of a patient's normal daily
      oral LTG dose. Thirteen blood samples were collected in each person over 96
      hours. SL-LTG and unlabeled LTG concentrations were measured simultaneously by
      gas chromatography-mass spectrometry. Concentration-time data were analyzed by
      nonlinear mixed-effects modeling (NONMEM version 7.3). RESULTS: Twenty-eight
      patients representing 16 young (18-48 years old) and 12 elderly (63-87 years old)
      patients were included, yielding 382 unlabeled and 351 SL-LTG concentrations. A
      two-compartment model with first-order absorption and elimination adequately
      described the plasma concentration-time data. Bioavailability of oral LTG was
      approximately 74% and did not differ by age. LTG clearance was 27.2% lower in
      elderly than in young patients (1.80 L/h for a 70-kg patient). SIGNIFICANCE:
      Although LTG bioavailability was not affected by age, LTG clearance was 27.2%
      lower in elderly versus young patients of comparable body weight, possibly
      indicating lower dosages being needed in this population.

PMID- 30101555
TI  - Hand Position and Response Assignment Modulate the Activation of the Valence
      Space Conceptual Metaphor.
AB  - Conceptual metaphor is ubiquitous in language and thought, as we usually reason
      and talk about abstract concepts in terms of more concrete ones via metaphorical
      mappings that are hypothesized to arise from our embodied experience. One
      pervasive example is the conceptual projection of valence onto space, which
      flexibly recruits the vertical and lateral spatial frames to gain structure
      (e.g., good is up-bad is down and good is right-bad is left). In the current
      study, we used a valence judgment task to explore the role that exogenous bodily
      cues (namely response hand positions) play in the allocation of spatial attention
      and the modulation of conceptual congruency effects. Experiment 1 showed that
      congruency effects along the vertical axis are weakened when task conditions
      (i.e., the use of vertical visual cues, on the one hand, and the horizontal
      alignment of responses, on the other) draw attention to both the vertical and
      lateral axes making them simultaneously salient. Experiment 2 evidenced that the
      vertical alignment of participants' hands while responding to the task-regardless
      of the location of their dominant hand-facilitates the judgment of positive and
      negative-valence words, as long as participants respond in a metaphor-congruent
      manner (i.e., up responses are good and down responses are bad). Overall, these
      results support the claim that source domain representations are dynamically
      activated in response to the context and that bodily states are an integral part
      of that context.

PMID- 30101557
TI  - Insights into Mechanochemical Reactions at Targetable and Stable, Sub-ambient
      Temperatures.
AB  - We provide insights into the effects of stable and verifiable, low-temperature
      conditions on mechanochemical reactions. These are made possible by modifications
      made to a SPEX 8000 m Mixer/mill allowing reliable fine control of low
      temperature mechanochemical reactions. Using the reduction of 4-tert
      butylcyclohexanone as a model system we find the diastereomeric product
      distribution bore a strong dependence on the selected temperature. The same
      reduction in methanol at room temperature shows similar stereoselectivity trends.
      In both cases decreasing temperature favors increases in selectivity, although
      the effect is more pronounced in the solvent-free mechanochemical conditions.
      These results indicate that the cooled jar provides a heatsink to mitigate the
      exothermic character of the reaction. Stereoselectivity also showed a dependence
      on operating frequency, although the nature of this dependence remains unclear.
      Applications of our reactor extend far beyond what is presented herein.

PMID- 30101559
TI  - In Vitro Hemocompatibility Evaluation of Ventricular Assist Devices in Pediatric
      Flow Conditions: A Benchmark Study.
AB  - Development of pediatric ventricular assist devices (VADs) has significantly
      lagged behind that of adult devices. This frustrating reality is reflected by the
      fact that the Berlin Heart EXCOR VAD is currently the only approved pediatric
      specific device in the USA. An alternative option is an off-label use of adult
      continuous-flow VADs, such as HeartMate II (HMII), which inevitably causes
      patient-device size mismatch in small children. We sought to conduct in vitro
      hemocompatibility testing in a pediatric flow condition, with a specific aim to
      provide benchmark values for future pediatric device development. Given the
      aforementioned fact that both pulsatile and continuous-flow devices are being
      used in the pediatric population, we opted to test both types of devices in the
      present study. The EXCOR and HMII blood pumps were tested using bovine blood
      under constant hemodynamic conditions (flow rate, Q = 2.5 +/- 0.25L/min;
      differential pressure across the pump, DeltaP = 68 +/- 5mm Hg). Hemolysis was
      measured by Harboe assay. There was a steady increase in plasma free hemoglobin
      during in vitro testing, with a statistically significant difference between 5
      and 360 min for both EXCOR (P < 0.0001) and HMII (P < 0.001). However, the degree
      of an increase in plasma free hemoglobin was more significant with HMII (P <
      0.001). Normalized index of hemolysis for EXCOR and HMII were 0.003 +/-
      0.0026g/100 L and 0.085 +/- 0.0119g/100 L, respectively. There was also a steady
      increase in platelet activation detected by CAPP2A antibody using flow cytometry,
      with a statistically significant difference between 5 and 360 min for both
      devices (P < 0.05). The degree of an increase in platelet activation was similar
      between the two devices (P = 0.218). High molecular weight von Willebrand factor
      (HMW vWF) multimer degradation measured by immunoblotting was evident for both
      devices, however, it was more pronounced with the EXCOR. EXCOR blood samples from
      all three time points (120, 240, and 360 min) were significantly different from
      the baseline (5 min), whereas only 360 min samples had a significant difference
      from the baseline with the HMII. In conclusion, we have observed similarities and
      differences in hemocompatibility profiles between the EXCOR and HMII, both of
      which are commonly used in the pediatric population. We anticipate the benchmark
      values in the present study will facilitate future pediatric VAD development.

PMID- 30101558
TI  - An HPLC-MS/MS method for the simultaneous determination of luteolin and its major
      metabolites in rat plasma and its application to a pharmacokinetic study.
AB  - A selective and accurate HPLC-MS/MS method was established to simultaneously
      quantify luteolin and its active metabolites (diosmetin, chryseriol, and luteolin
      7-O-glucuronide) in rat plasma. The analytes were separated on a C18 column with
      a mobile phase of water containing 0.5% formic acid and acetonitrile under
      gradient elution to shorten the total chromatographic run time and increase the
      resolution of diosmetin and chryseriol. A triple quadruple mass spectrometer
      coupled with an electrospray ionization source in the negative ion mode was used
      to detect the analytes. The multiple reaction monitoring transitions were of m/z
      284.9->132.9 for luteolin, m/z 298.9->283.9 for diosmetin and chryseriol, m/z
      461.1->284.9 for luteolin-7-O-glucuronide, and m/z 300.9->150.9 for the internal
      standard. The method was linear within the concentration ranges of 0.06-90 MUg/mL
      for luteolin, 0.03-12 MUg/mL for diosmetin, 0.015-4.8 MUg/mL for chryseriol, and
      0.06-60 MUg/mL for luteolin-7-O-glucuronide. The intra- and interday precisions
      were all within 6.0%. Accuracy ranged from -3.2 to 6.4%. The matrix effect and
      instability were not observed during bioanalysis. This method was used to study
      the pharmacokinetic characteristics of luteolin and its metabolites in rats after
      treatment with luteolin.

PMID- 30101560
TI  - Feasibility and accuracy of UF/NCI phantoms and Monte Carlo retrospective
      dosimetry in children treated on National Wilms Tumor Study protocols.
AB  - PURPOSE: This pilot study was done to determine the feasibility and accuracy of
      University of Florida/National Cancer Institute (UF/NCI) phantoms and Monte Carlo
      (MC) retrospective dosimetry and had two aims: (1) to determine the anatomic
      accuracy of UF/NCI phantoms by comparing 3D organ doses in National Wilms Tumor
      Study (NWTS) patient-matched UF/NCI phantoms to organ doses in corresponding
      patient-matched CT scans and (2) to compare infield and out-of-field organ
      dosimetry using two dosimetry methods-standard radiation therapy (RT) treatment
      planning systems (TPS) and MC dosimetry in these two anatomic models. METHODS:
      Twenty NWTS patient-matched Digital Imaging and Communications in Medicine
      (DICOM) files of UF/NCI phantoms and CT scans were imported into the Pinnacle RT
      TPS. The NWTS RT fields (whole abdomen, flank, whole lung, or a combination) and
      RT doses (10-45 Gy) were reconstructed in both models. Both TPS and MC dose
      calculations were performed. For aim 1, the mean doses to the heart, kidney,
      thyroid gland, testes, and ovaries using TPS and MC in both models were
      statistically compared. For aim 2, the TPS and MC dosimetry for these organs in
      both models were statistically compared. RESULTS: For aim 1, there was no
      significant difference between phantom and CT scan dosimetry for any of the
      organs using either TPS or MC dosimetry. For aim 2, there was a significant
      difference between TPS and MC dosimetry for both CT scan and phantoms for all
      organs. Although the doses for infield organs were similar for both TPS and MC,
      the doses for near-field and out-of-field organs were consistently higher for 90%
      to 100% of MC doses; however, the absolute dose difference was small (<1 Gy).
      CONCLUSIONS: This pilot study has demonstrated that the patient-matched UF/NCI
      phantoms together with MC dosimetry is an accurate model for performing
      retrospective 3D dosimetry in large-scale epidemiology studies such as the NWTS.

PMID- 30101561
TI  - Proactive community support tailored to holistic needs: A cohort study.
AB  - BACKGROUND: It is increasingly internationally recognized that a cancer diagnosis
      impacts on people practically and financially as well as physically and
      psychologically. It is less clear what to do about this. This study introduces an
      original community service designed to mitigate this wider impact. Nonclinical
      "link officers" use holistic needs assessment (HNA) to help newly diagnosed
      people identify and quantify the severity of their physical, psychological,
      practical, financial, and social concerns. A care plan is then agreed, usually
      involving community interventions from partner agencies. Following intervention,
      assessment is repeated. The primary aim of this study was to establish whether
      there was a significant difference between initial assessment and follow-up,
      postintervention. Secondary aim was to identify potential predictors of increased
      levels of concern at baseline and follow-up. METHOD: Pre- and postintervention
      observational cohort study. Paired t test examined the difference in mean (SD)
      concern severity between baseline and follow-up. Multiple linear regression
      models were computed to hypothesize potential predictors of initial concern
      severity and severity change. RESULTS: The service saw 2413 people 2014-2017.
      Participants identified average 5.5 (4.7) concerns, financial concerns being most
      frequent. Mean severity at baseline was 7.12 (out of 10) (2.50), reducing to 3.83
      (3.49) post-treatment, paired t(4454) = 64.68, P < 0.0001, reduction of 3.31 (95%
      CI 3.21-3.41). Factors associated with higher initial concern included
      unemployment and caring responsibilities. Unemployment was also associated with a
      smaller reduction of concern severity at follow-up. CONCLUSION: Patient level of
      concern went from a level associated with specialist referral to a much more
      manageable level. This original finding is internationally significant because it
      extends Khera et al's (2017) "provocative idea" that all patients should be
      screened for financial problems to show that they can be helped with all their
      concerns. This article describes a successful, transferable model of community
      care.

PMID- 30101562
TI  - Enzyme therapy for functional bowel disease-like post-prandial distress.
AB  - Post-prandial gastrointestinal symptoms such as diarrhea, abdominal distension,
      flatulence, bloating and a feeling of fullness are common complaints of often
      unknown etiology and pathogenesis. There is a long history of trials reporting
      the successful use of products containing a variety of combinations of digestive
      enzymes including a number of randomized placebo-controlled trials. We provide a
      narrative review of studies describing the use of multi-digestive enzymes for
      symptoms consistent with irritable bowel syndrome. We describe clinical trials
      reported over the past 60 years including double-blinded randomized, placebo
      controlled studies and recent trials that focused on post-prandial diarrhea
      consistent with diarrhea-predominant irritable bowel syndrome. Disaccharidase
      deficiencies or deficiencies of other carbohydrate digesting enzymes were
      excluded. Worldwide studies have generally reported success with multi-enzyme
      preparations although none used a factorial design to identify subgroups or
      attempted to link specific symptom responses to specific components of therapy.
      Although there is a long history of the successful use of multi-enzyme
      preparations for post-prandial symptoms consistent with irritable bowel syndrome,
      long-term studies using validated scoring systems and factorial designs are
      needed to confirm the results for specific symptoms and the components of the
      combination drugs received.

PMID- 30101563
TI  - Ustekinumab exposure during conception and pregnancy in patients with chronic
      plaque psoriasis: a case series of 10 pregnancies.

PMID- 30101564
TI  - Phylogeography of the widespread creek chub Semotilus atromaculatus
      (Cypriniformes: Leuciscidae).
AB  - The extent and nature of genetic differentiation in Semotilus atromaculatus, one
      of the most abundant and widespread leuciscids in North America, were evaluated
      based on mitochondrial (mt) and nuclear DNA sequence variation. Phylogenetic
      relationships were first inferred based on a fragment of the cytochrome b (cytb)
      region and the nuclear intron s7 gene for S. atromaculatus and all other
      congeners as well as representative species from all other genera in the creek
      chub-plagopterin clade. The phylogeography of major haplogroups of S.
      atromaculatus was also assessed according to variation in a fragment of the
      mitochondrial cytb region from 567 individuals across its range. All analyses
      identified S. thoreauianus, S. lumbee and S. corporalis as reciprocally
      monophyletic groups. Analyses of nuclear sequence variation resolved S.
      atromaculatus as a single clade, where S. thoreauianus and S. lumbee were
      recovered as the sister group to S. atromaculatus, and S. corporalis was resolved
      as sister to all other species in the genus. Analyses of mtDNA sequence variation
      recovered S. atromaculatus as three well supported and differentiated
      monophyletic groups, with a widespread genetically homogeneous lineage extending
      across most of the current range of the species; a more geographically restricted
      and geographically structured lineage in the southern Appalachians, sister group
      to S. lumbee; and a geographically restricted lineage was identified from two
      Gulf Slope basins. Evidence of complex mito-nuclear discordance and
      phylogeographic differentiation within S. atromaculatus illustrates that further
      analysis of widespread species is warranted to understand North American
      freshwater fish diversity and distributions.

PMID- 30101565
TI  - Wnt signaling in bone, kidney, intestine, and adipose tissue and interorgan
      interaction in aging.
AB  - Over the last two decades, it has become increasingly apparent that Wnt signaling
      plays a critical role in development and adult tissue homeostasis in multiple
      organs and in the pathogenesis of many diseases. In particular, a crucial role
      for Wnt signaling in bone development and bone tissue homeostasis has been well
      recognized. Numerous genome-wide association studies confirmed the importance of
      Wnt signaling in controlling bone mass. Moreover, ample evidence suggests that
      Wnt signaling is essential for kidney, intestine, and adipose tissue development
      and homeostasis. Recent emerging evidence demonstrates that Wnt signaling may
      play a fundamental role in the aging process of those organs. New discoveries
      show that bone is not only the major reservoir for calcium and phosphate storage,
      but also the largest organ with multiple functions, including mineral and energy
      metabolism. The interactions among bone, kidney, intestine, and adipose tissue
      are controlled and regulated by several endocrine signals, including FGF23,
      klotho, sclerostin, osteocalcin, vitamin D, and leptin. Since the aging process
      is characterized by structural and functional decline in almost all tissues and
      organs, understanding the Wnt signaling-related interactions among bone, kidney,
      intestine, and adipose tissue in aging may shed light on the pathogenesis of age
      related diseases.

PMID- 30101567
TI  - Education for biometry in practice.

PMID- 30101568
TI  - Changes in annual incidence of school children with type 2 diabetes in the Tokyo
      Metropolitan Area during 1975-2015.
AB  - OBJECTIVE: To analyze changes in the annual incidence of school students with
      type 2 diabetes detected by urine glucose screening at schools in the Tokyo
      Metropolitan Area during 1975-2015. METHODS: Trend in temporal changes in the
      annual incidence rate were analyzed using a joinpoint regression model and the
      joinpoints. Annual percent change (APC) was calculated for each segmented line
      regression. Average annual percent change (AAPC) was also calculated for the
      whole period analyzed. RESULTS: In total, 301 students, including 64 primary
      school students and 237 junior high school students, were diagnosed with type 2
      diabetes. The overall incidence of type 2 diabetes (per 100 000/year) during the
      entire study period was 2.58 in all students, 0.80 in primary school students,
      and 6.41 in junior high school students. AAPC during the entire study period was
      estimated at -1.5 (not significant), and the incidence significantly increased
      during 1975-1982 (APC = 17.49, P < 0.05), but tended to decrease during 1982-2015
      (APC = -1.01). In primary school students, the incidence significantly increased
      during1975-2010 (APC = 3.30, P < 0.05), and tended to decrease during 2010-2015
      (APC = -29.61). In junior high school students, the incidence did not
      significantly change during the entire study period (APC = 0.06). CONCLUSIONS: We
      found increasing trend in the overall incidence of school students with type 2
      diabetes during 1975-1982, but a decreased tendency in recent years. This could
      be due to changes observed during the same time period in the primary school
      students. Lifestyle changes might contribute to improved incidence of childhood
      type 2 diabetes.

PMID- 30101566
TI  - Dynamic RNA holo-editosomes with subcomplex variants: Insights into the control
      of trypanosome editing.
AB  - RNA editing causes massive remodeling of the mitochondrial mRNA transcriptome in
      trypanosomes and related kinetoplastid protozoa. This type of editing involves
      the specific insertion or deletion of uridylates (U) directed by small noncoding
      guide RNAs (gRNAs). Because U-insertion exceeds U-deletion by a factor of 10,
      editing increases the nascent mRNA size by up to 55%. In Trypanosoma brucei, the
      editing apparatus uses ~40 proteins and >1,200 gRNAs to create the functional
      open reading frame in 12 mRNAs. Thousands of sites are specifically recognized in
      the pre-edited mRNAs and a myriad of partially edited transcript intermediates
      accumulates in mitochondria. The control of editing is poorly understood, but
      past work suggests that it occurs during substrate recognition, the initiation
      and progression of editing, and during the life-cycle in different hosts. The
      growing understanding of the editing proteins offers clues about editing control.
      Most editing proteins reside in the "RNA-free" RNA editing core complex (RECC)
      and in the accessory RNA editing substrate complex (RESC) that contains gRNA. Two
      accessory RNA helicases are known, including one in the RNA editing helicase 2
      complex (REH2C). Both the RESC and the REH2C associate with mRNA, providing a
      rationale for the assembly of mRNA or its mRNPs, RESC, and the RECC enzyme.
      Identified variants of the canonical editing complexes further complicate the
      model of RNA editing. We examine specific examples of complex variants,
      differential effects of editing proteins on the mRNAs within and between T.
      brucei life stages, and possible control points in RNA holo-editosomes. This
      article is categorized under: RNA Processing > RNA Editing and Modification RNA
      Interactions with Proteins and Other Molecules > RNA-Protein Complexes RNA
      Interactions with Proteins and Other Molecules > Protein-RNA Interactions:
      Functional Implications.

PMID- 30101569
TI  - All-Solution-Processed Pure Formamidinium-Based Perovskite Light-Emitting Diodes.
AB  - All-solution-processed pure formamidinium-based perovskite light-emitting diodes
      (PeLEDs) with record performance are successfully realized. It is found that the
      FAPbBr3 device is hole dominant. To achieve charge carrier balance, on the anode
      side, PEDOT:PSS 8000 is employed as the hole injection layer, replacing PEDOT:PSS
      4083 to suppress the hole current. On the cathode side, the solution-processed
      ZnO nanoparticle (NP) is used as the electron injection layer in regular PeLEDs
      to improve the electron current. With the smallest ZnO NPs (2.9 nm) as electron
      injection layer (EIL), the solution-processed PeLED exhibits a highest forward
      viewing power efficiency of 22.3 lm W-1 , a peak current efficiency of 21.3 cd A
      1 , and an external quantum efficiency of 4.66%. The maximum brightness reaches a
      record 1.09 * 105 cd m-2 . A record lifetime T50 of 436 s is achieved at the
      initial brightness of 10 000 cd m-2 . Not only do PEDOT:PSS 8000 HIL and ZnO NPs
      EIL modulate the injected charge carriers to reach charge balance, but also they
      prevent the exciton quenching at the interface between the charge injection layer
      and the light emission layer. The subbandgap turn-on voltage is attributed to
      Auger-assisted energy up-conversion process.

PMID- 30101570
TI  - Variation in the regulatory region of FZP causes increases in secondary
      inflorescence branching and grain yield in rice domestication.
AB  - Inflorescence branching is a key agronomic trait determining rice yield. The
      primary branch of the ancestral wild rice (Oryza rufipogon Griff.) bears few
      grains, due to minimal secondary branching. By contrast, Oryza sativa cultivars
      have been selected to produce large panicles with more secondary branches. Here
      we showed that the CONTROL OF SECONDARY BRANCH 1 (COS1) gene, which is identical
      to FRIZZY PANICLE (FZP), plays an important role in the key transition from few
      secondary branches in wild rice to more secondary branches in domesticated rice
      cultivars. A 4-bp tandem repeat deletion approximately 2.7 kb upstream of FZP may
      affect the binding activities of auxin response factors to the FZP promoter,
      decrease the expression level of FZP and significantly enhance the number of
      secondary branches and grain yield in cultivated rice. Functional analyses showed
      that NARROW LEAF 1 (NAL1), a trypsin-like serine and cysteine protease,
      interacted with FZP and promoted its degradation. Consistently, downregulating
      FZP expression or upregulating NAL1 expression in the commercial cultivar
      Zhonghua 17 increased the number of secondary branches per panicle, grain number
      per panicle and grain yield per plant. Our findings not only provide insights
      into the molecular mechanism of increasing grain number and yield during rice
      domestication, but also offer favorable genes for improving the grain yield of
      rice.

PMID- 30101571
TI  - Early compensatory responses against neuronal injury: A new therapeutic window of
      opportunity for Alzheimer's Disease?
AB  - Alzheimer's disease (AD) is characterized by extensive neurodegeneration and
      inflammation in selective brain areas, linked to severely disabling cognitive
      deficits. Before full manifestation, different stages appear with progressively
      increased brain pathology and cognitive impairment. This significantly extends
      the time lag between initial molecular triggers and appearance of detectable
      symptoms. Notably, a number of studies in the last decade have revealed that in
      the early stage of mild cognitive impairment, events that appear in contrast with
      neuronal distress may occur. These have been reproduced in vitro and in animal
      models and include increase in synaptic elements, increase in synaptic and
      metabolic activity, enhancement of neurotrophic milieu and changes in glial cell
      reactivity and inflammation. They have been interpreted as compensatory responses
      that could either delay disease progression or, in the long run, result
      detrimental. For this reason, these mechanisms define a new and previously
      undervalued window of opportunity for intervention. Their importance resides
      especially in their early appearance. Directing efforts to better characterize
      this stage, in order to identify new pharmacological targets, is an exciting new
      avenue to future advances in AD research.

PMID- 30101572
TI  - The pediatric version of the eating assessment tool-10 has discriminant ability
      to detect aspiration in children with neurological impairments.
AB  - BACKGROUND: The aim of this study was to determine the ability of the Pediatric
      version of the Eating Assessment Tool-10 (PEDI-EAT-10) to detect aspiration in
      children with neurological impairments. METHODS: Two hundred and fifty-four
      children were included. Swallowing function was imaged with videofluoroscopic
      swallowing study (VFSS). The penetration and aspiration scale (PAS) was used to
      determine the penetration and aspiration severity. Parents completed the PEDI-EAT
      10, which is a 10 item, reliable, and valid dysphagia symptom specific outcome
      instrument. KEY RESULTS: The mean age of children was 59.91 +/- 55.33 months (min
      = 18, max = 315), of which 52.8% were male. The mean PEDI-EAT-10 of children with
      airway aspiration (PAS > 5) was 22.32 +/- 10.73 (min = 0, max = 40) and the mean
      PEDI-EAT-10 of children who did not have aspiration (PAS < 6) was 12.35 +/- 8.64
      (min = 0, max = 40). A linear correlation was found between PEDI-EAT-10 and PAS
      scores of children (r = 0.41, P < 0.001). The sensitivity of a PEDI-EAT-10 score
      greater than 12 in predicting aspiration was 77% and the specificity was 54%. A
      PEDI-EAT-10 score greater than 12 has a positive predictive value of 69% and a
      negative predictive value of 64%. CONCLUSIONS AND INFERENCES: The PEDI-EAT-10
      could be used to detect unsafe airway issues to identify and refer children for
      further instrumental swallowing evaluation.

PMID- 30101573
TI  - Comparing differences in support needs as perceived by parents of adult offspring
      with down syndrome, autism spectrum disorder and cerebral palsy.
AB  - BACKGROUND: Parents often face many barriers when taking care of their offspring
      with disabilities. In childhood, support needs vary with families of children
      with Down syndrome often reporting less caregiving challenges. However, it is
      unclear whether support needs vary in adulthood. This study compared parents of
      adults with Down syndrome (DS), autism spectrum disorder (ASD) and cerebral palsy
      (CP) regarding support needs of their offspring with intellectual and
      developmental disabilities (IDD) and their families. METHOD: Data were collected
      via a national survey in the United States with 189 parents of adults with IDD.
      RESULTS: Across the quantitative and qualitative analyses, parents of adults with
      DS (versus CP and ASD) reported significantly greater recreational, natural
      supports, more formal services and less future planning barriers. CONCLUSION: The
      results indicate that the DS advantage may persist in adulthood regarding support
      needs. More research is needed to understand different types of support needs.

PMID- 30101574
TI  - Robotic rectal surgery has advantages over laparoscopic surgery in selected
      patients and centres.

PMID- 30101575
TI  - Natural mortality factors of tomato leafminer Tuta absoluta in open-field tomato
      crops in South America.
AB  - BACKGROUND: Little importance has been given to the role of natural mortality
      factors (biotic and abiotic) in the regulation of tomato leafminer Tuta absoluta
      (Lepidoptera: Gelechiidae) populations. The present study determined the action
      of mortality factors on T. absoluta populations infesting cultivated tomato
      crops. Eighty ecological life tables for T. absoluta in field cultivated tomato
      plants were constructed and analyzed. RESULTS: Total T. absoluta mortality was
      99.08%, with 38.76% mortality during the egg phase, 57.20% in the larva phase and
      3.12% in the pupal phase. The main mortality factors during the egg stage were
      predation, parasitism and egg inviability. In the larval stage, the main
      mortality factors were predation, parasitism, entomopathogenic agents and
      physiological disorders. In the pupal stage, the main mortality factor was
      predation. The larvae of the third and fourth instar were more susceptible to the
      action of mortality factors and the predatory wasp, Protonectarina sylveirae, was
      the main insect predator of these larvae. CONCLUSIONS: The T. absoluta population
      is regulated under field conditions by the action of natural enemies of the
      larvae. The predatory wasp P. sylveirae is very important in the regulation of T.
      absoluta populations in open-field tomato crops in Brazil. (c) 2018 Society of
      Chemical Industry.

PMID- 30101576
TI  - Complementary feeding practices among rural Bangladeshi mothers: Results from
      WASH Benefits study.
AB  - Inappropriate complementary feeding contributes to linear growth faltering in
      early childhood. Behaviour change interventions have been effective at improving
      practice, but few studies have investigated the effects of multicomponent
      integrated interventions. We conducted a cluster-randomized controlled trial in
      rural Bangladesh in which geographic clusters were randomized into seven arms:
      water treatment (W), sanitation (S), handwashing (H), water, sanitation, and
      handwashing (WSH), improved nutrition with infant and young child feeding
      messages and lipid-based nutrient supplementation for 6- to 24-month olds (N),
      N+WSH, and control. The objective of this paper was to examine the independent
      and combined effects of interventions on indicators of complementary feeding.
      Approximately 1 and 2 years after initiation of the intervention, research
      assistants surveyed mothers about infant feeding practices. Complementary feeding
      was examined using the World Health Organization indicators of infant and young
      child feeding practices. We used Poisson regression models to estimate prevalence
      ratios and linear regression models for prevalence differences with clustered
      sandwich estimators to adjust for clustering. A total of 4,718 households from
      720 clusters were surveyed at year 1 and 4,667 at year 2. The children in the
      nutrition arms had a higher prevalence of meeting the minimum dietary diversity
      score compared with controls (year 1: N: 66.4%; N+WSH: 65.0% vs. C:32.4%; year 2:
      N: 91.5%; N+WSH: 91.6% vs. C:77.7%). Children in the nutrition arms received
      diverse food earlier than the children in control arm. In addition, the average
      consumption of lipid-based nutrient supplementation was >90% in each follow-up.
      Nutrition-specific interventions could be integrated with nutrition-sensitive
      interventions such as WSH without compromising the uptake of the nutrition
      intervention.

PMID- 30101577
TI  - The achievement of boar sperm in vitro capacitation is related to an increase of
      disrupted disulphide bonds and intracellular reactive oxygen species levels.
AB  - The aim of this work was to determine the relationship of intracellular reactive
      oxygen species (ROS) and the disulphide bonds established between sperm proteins
      with the achievement of capacitation in boar spermatozoa. With this purpose,
      spermatozoa were incubated in a specifically designed in vitro capacitation
      medium (CM) in the presence or absence of reduced glutathione (GSH). Incubation
      of boar spermatozoa in CM for 4 h significantly (p < 0.05) increased free
      cysteine residues, which is a marker of disrupted disulphide bonds, and also
      intracellular ROS levels. The addition of GSH to the medium prevented most
      capacitation-like changes in sperm motility, membrane lipid disorder,
      mitochondrial membrane potential, intracellular calcium levels and localization
      of tyrosine-phosphorylated proteins (pTyr), but not in tyrosine phosphorylation
      of P32. These effects were accompanied by the inhibition of the ability of sperm
      cells to trigger the acrosome exocytosis in response to progesterone. When GSH
      was added together with progesterone after 4 h of incubation, acrosome exocytosis
      was not altered, but the subsequent decrease in intracellular calcium observed in
      controls cells was inhibited. Furthermore, co-incubation of oocytes with
      spermatozoa previously incubated in CM in the presence of GSH for 4 h
      significantly (p < 0.05) increased the number of spermatozoa attached to the
      oocyte surface but decreased normal fertilization rates. Our results suggest that
      boar sperm capacitation is related to an increase in disrupted disulphide bonds
      and intracellular ROS levels and that both events are related to the regulation
      of hyperactivated motility, intracellular calcium dynamics, sperm binding ability
      to the oocyte and achievement of proper nuclear decondensation upon oocyte
      penetration.

PMID- 30101579
TI  - Obesity without comorbidity may also lead to non-thyroidal illness syndrome.
AB  - BACKGROUND: Obesity mediates a series of operations in the body by increasing the
      production of proinflammatory cytokines. Cytokines play an important role in the
      development of non-thyroidal illness syndrome (NTIS). OBJECTIVES: The aim of this
      study was to investigate the association between obesity and NTIS. MATERIAL AND
      METHODS: A total of 423 subjects were included. The study group was comprised of
      219 obese patients without any comorbid disease and the control group was
      comprised of 204 healthy subjects. Body mass index (BMI), thyroid hormone levels,
      high-sensitivity C-reactive protein (hs-CRP) levels, erythrocyte sedimentation
      rate (ESR), complete blood count, and other biochemical parameters were measured.
      Frequencies of NTIS were calculated. MedCalc 12.5 software program (MedCalc,
      Ostend, Belgium) was used for statistical analysis. RESULTS: Groups were
      statistically different according to BMI (p < 0.001). The mean BMIs of the study
      and the control group were 34.6 +/-5.0 kg/m2 and 22.6 +/-1.8 kg/m2, respectively.
      Obese patients had higher serum hs-CRP levels, ESR and white blood cells (WBC)
      levels (0.99 +/-3.17 mg/L vs 0.39 +/-1.09 mg/L; 17.2 +/-10.6 mm/h vs 12.6 +/-8.0
      mm/h; 7.8 +/-2.1 103/MUL vs 6.9 +/-1.5 103/MUL, respectively; p < 0.001). There
      were 21 (9.5%) obese patients with NTIS, while there were none NTIS cases in the
      control group. The difference was statistically significant (p < 0.001). There
      was a strong association between obesity and NTIS (odds ratio (OR) = 44.2,
      confidence interval (CI) = 95% 2.66-736.3; p = 0.0082). CONCLUSIONS:
      Inflammation, which is strongly associated with adipose tissue, may lead to NTIS
      in obese patients without any comorbid disease.

PMID- 30101580
TI  - Performance of a newly developed mineral gel system on erosive and
      erosive/abrasive enamel loss. An in vitro study
AB  - We compared the prevention of erosive and erosive/abrasive enamel loss by a
      medical minerals gel system (R.O.C.S.) to that by an anti-erosive toothpaste.
      Seventy-two bovine enamel samples were randomly allocated to six groups (E1-E3
      and EA1-EA3; n=12). Per day, samples were eroded (2 min) 9 times using HCl (pH
      2.6). Between erosive challenges and over night samples were stored in artificial
      saliva. Per day, samples were stored (100 s; groups E1-E3) or additionally
      brushed (20 brushing strokes; groups EA1-EA3) in/with slurries prepared from
      artificial saliva plus: no additional toothpaste (control groups E1 and EA1),
      elmex erosion protection toothpaste (groups E2 and EA2), or R.O.C.S. toothpaste
      (groups E3 and EA3). Once per day, samples of groups E3 and EA3 were additionally
      treated (40 min) with a slurry prepared from artificial saliva and R.O.C.S.
      medical minerals gel. After 7, 14 and 21 days enamel loss was measured by surface
      profilometry and analyzed by Kruskal-Wallis tests and Conover post-hoc tests.
      Under erosive conditions only (groups E1-E3), at each time point of measurement
      the significantly lowest enamel loss was observed in group E2. Substance loss in
      group E3 was significantly higher, but significantly lower compared to that of
      group E1. Under erosive/abrasive conditions (groups EA1-EA3), at each time point
      of measurement the significantly lowest enamel wear was observed in group EA2.
      Wear in group EA3 was significantly higher even compared to that of group EA1.
      The tested R.O.C.S. medical minerals gel system was able to reduce erosive enamel
      loss but not erosive/abrasive enamel wear, and it was less effective than the
      elmex erosion protection toothpaste.

PMID- 30101578
TI  - Peptide-Gold Nanoparticle Hybrids as Promising Anti-Inflammatory Nanotherapeutics
      for Acute Lung Injury: In Vivo Efficacy, Biodistribution, and Clearance.
AB  - Gold nanoparticles (GNPs) have shown great promises in various biomedical
      applications. Although GNPs exhibit excellent therapeutic efficacy in in vitro
      and in vivo in numerous studies, there still exists significant biosafety
      concerns, mainly for their nonbiodegradability and tendency to be trapped in the
      liver and spleen. To tackle this problem, hexapeptides are utilized to modify the
      GNP surface to not only impart them with potent anti-inflammatory activity, but
      also facilitate their rapid clearance in vivo. Previously, a unique class of
      peptide-GNP hybrids that potently inhibit multiple TLR signaling pathways in
      macrophages was identified; in this work, it is further demonstrated that these
      hybrids, after intratracheal instillation, are capable of effectively reducing
      lung inflammation and injury by decreasing neutrophil infiltration and increasing
      the number of regulatory T cells in the lung in a lipopolysaccharide-induced
      acute lung injury (ALI) mouse model. More importantly, these hybrids can be
      effectively excreted 26 h post-administration with only 8.49 +/- 0.70% of them
      remaining in the body, primarily in the lung and intestine and less than 0.03%
      accumulated in the liver and spleen. This work provides strong evidences that
      properly designed peptide-GNP hybrids can serve as the next generation of
      effective and safe anti-inflammatory nanotherapeutics to treat ALI.

PMID- 30101581
TI  - Engineering of Hollow PdPt Nanocrystals via Reduction Kinetic Control for Their
      Superior Electrocatalytic Performances.
AB  - Synthesis of hollow metal nanocrystals (NCs) is greatly attractive for their high
      active surface areas, which gives rise to excellent catalytic activity. Taking
      PdPt alloy nanostructure as an example, we designed a synthetic tactic for the
      preparation of hollow metal nanostructures by delicate control over the
      difference in the reduction kinetic of metal precursors. At a high reduction rate
      difference, the Pd layer forms from H2PdCl4 and is subsequently etched, leading
      to the formation of a hollow space. A solid PdPt structure is achieved when the
      reduction rate of Pd and Pt precursor is comparable. Obviously, the hollow space
      and composition are tunable as well by adjusting the reduction rate difference.
      More importantly, the prepared hollow PdPt nanostructures exhibit a branched
      outer, porous wall, and rough hollow interior. The branched outer and rough
      hollow interior provide the higher density of unsaturated atoms, whereas the
      porous wall serves as channels connecting the inner, outer, and reactive agents.
      Moreover, the periodic self-consistent density function theory suggests that the
      d-band theory density of state of the PdPt nanoalloys is upshifted in comparison
      to the monometallic component, which will beneficial for improvement in their
      catalytic performances. Electrocatalytic tests reveal that the PdPt bimetallic
      NCs, especially for Pt32Pd68 nanostructures, show excellent catalytic activity
      and stability toward methanol oxidation reaction owing to their special
      structures as well as compositions.

PMID- 30101582
TI  - Synthesis of 2-Arylindoles through Pd(II)-Catalyzed Cyclization of Anilines with
      Vinyl Azides.
AB  - Vinly azides are featured as electrophiles, nucleophiles, and radical acceptors
      in synthetic chemistry and have emerged as rapid and versatile synthons in the
      preparation of N-heterocyclic systems. Herein, a novel approach to 2-arylindoles
      via Pd(II)-catalyzed cyclization reaction of anilines with vinyl azides has been
      achieved, which furnishes the versatile 2-arylindoles with high efficieny and
      excellent regioselectivity.

PMID- 30101583
TI  - Rare Medium-Sized Rings Prepared via Hydrolytic Imidazoline Ring Expansion
      (HIRE).
AB  - The hydrolytic imidazoline ring expansion (HIRE) methodology was extended to
      readily available tetracyclic [1,4]thiazepines as well as sulfoxide and sulfone
      analogs thereof. The reactions resulted in the facile formation of a rare medium
      sized [1,4,7]thiazecine ring system that has an emerging utility in bioactive
      compound design. Comparing the HIRE rates for representative compounds in the
      three groups of substrates allowed drawing some generalizations about the
      substituent effects on the course of the reaction.

PMID- 30101584
TI  - Highly Dispersed Co-B/N Codoped Carbon Nanospheres on Graphene for Synergistic
      Effects as Bifunctional Oxygen Electrocatalysts.
AB  - Oxygen reduction and evolution reactions as two important electrochemical energy
      conversion processes in metal-air battery devices have aroused widespread
      concern. However, synthesis of low-cost non-noble metal-based bifunctional high
      performance electrocatalysts is still a great challenge. In this work, we report
      on the design and synthesis of a novel Co-B/N codoped carbon with core-shell
      structured nanoparticles aligned on graphene nanosheets (denoted as CoTIB-C/G)
      derived from cobalt tetrakis(1-imidazolyl)borate (CoTIB) and graphene oxide
      hybrid template. Compared with pristine CoTIB-derived bulk structure (CoTIB-C),
      CoTIB-C/G particles with an average size of 25 nm are uniformly dispersed on
      highly conductive graphene sheets in the hybrid material, thus dramatically
      increasing the utilization efficiency and activity of the active components upon
      oxygen reduction and evolution. After all, because of the "barrier effect" of
      graphene sheets toward CoTIB-C/G and the synergistic effect between Co
      nanoparticles and carbon shells linked to the graphene sheets, as well as
      heteroatoms' doping effect, the as-obtained bifunctional electrocatalyst exhibits
      remarkable oxygen reduction and evolution reaction activities in alkaline media,
      indicating its feasibility and potential in practical applications.

PMID- 30101586
TI  - Detail Photophysical Studies of Sulfonated Polyaniline in Aqueous Medium.
AB  - Sulfonated polyaniline (SPANI) has emerged as a promising polymer in the past few
      decades due to its solubility in water and relatively moderate conductivity.
      However, to date, literature data on the optical characterization of SPANI are
      very limited and preliminary in nature. In the present work, SPANI is synthesized
      by direct sulfonation of emeraldine salt form of polyaniline with chlorosulfonic
      acid in an inert solvent. Detail photophysical properties of SPANI are
      investigated in aqueous medium by using steady state (concentration, temperature,
      pH, and excitation wavelength dependence) and time-resolved spectroscopic
      techniques. The steady state fluorescence emission measurements are carried out
      carefully to avoid inner filter effect (especially secondary inner filter effect
      or reabsorption effect) as well as scattering. Two ground state conformations of
      SPANI are suggested to exist in aqueous medium. Excitation wavelength dependence
      of the fluorescence emission spectra is attributed to red-edge effect. All these
      observations are nicely corroborated by the fluorescence lifetime data of SPANI
      obtained from time-resolved measurements. All these new findings are extremely
      important in view of the potential applications of SPANI in polymer
      optoelectronics.

PMID- 30101585
TI  - Metal-Free C(sp3)-H Azidation in a Radical Strategy for the Synthesis of 3-Azido
      2-oxindoles at Room Temperature.
AB  - A novel and environmentally attractive C(sp3)-H azidation of 2-oxindoles
      involving the formation of a C-N bond was developed. This methodology achieved
      for the first time 3-azido-2-oxindole construction under metal-free conditions at
      room temperature via a radical strategy. PhI(OAc)2 was used as the oxidant and
      Et3N was used as the additive in this transformation. Furthermore, the
      mechanistic study indicated that this azidation involved a radical process.

PMID- 30101587
TI  - Density-Gradient Control over Nanoparticle Supercrystal Formation.
AB  - With the advent of DNA-directed methods to form "single crystal" nanoparticle
      superlattices, new opportunities for studying the properties of such structures
      across many length scales now exist. These structure-property relationships rely
      on the ability of one to deliberately use DNA to control crystal symmetry,
      lattice parameter, and microscale crystal habit. Although DNA-programmed
      colloidal crystals consistently form thermodynamically favored crystal habits
      with a well-defined symmetry and lattice parameter based upon well-established
      design rules, the sizes of such crystals often vary substantially. For many
      applications, especially those pertaining to optics, each crystal can represent a
      single device, and therefore size variability can significantly reduce their
      scope of use. Consequently, we developed a new method based upon the density
      difference between two layers of solvents to control nanoparticle superlattice
      formation and growth. In a top aqueous layer, the assembling particles form a
      less viscous and less dense state, but once the particles assemble into well
      defined rhombic dodecahedral superlattices of a critical size, they sediment into
      a higher density and higher viscosity sublayer that does not contain particles
      (aqueous polysaccharide), thereby arresting growth. As a proof-of-concept, this
      method was used to prepare a uniform batch of Au nanoparticle (20.0 +/- 1.6 nm in
      diameter) superlattices in the form of 0.95 +/- 0.20 MUm edge length rhombic
      dodecahedra with body-centered cubic crystal symmetries and a 49 nm lattice
      parameter (cf. 1.04 +/- 0.38 MUm without the sublayer). This approach to
      controlling and arresting superlattice growth yields structures with a 3-fold
      enhancement in the polydispersity index.

PMID- 30101589
TI  - Silica-Nanochannel-Based Interferometric Sensor for Selective Detection of Polar
      and Aromatic Volatile Organic Compounds.
AB  - Public awareness of the toxicity of volatile organic compounds (VOCs) has led to
      increased requirements for direct measurement of these substances. This work
      reports the sensitive detection of VOCs at the ppb level by an interferometric
      sensor based on the multilayer silica-nanochannel membrane (MSNM). The MSNM is
      fabricated by layer-by-layer stacking of a free-standing ultrathin SNM composed
      of regularly ordered channels with an ultrasmall diameter of about 2.3 nm and an
      ultrahigh density of about 4 * 1012 cm-2. Light reflected from parallel
      interfaces of the MSNM gives rise to the interferometric pattern with
      constructive and destructive fringes. The adsorption of VOCs to a highly porous
      MSNM varies the refractive index of the MSNM, resulting in the shift of the
      reflectometric interference spectrum (RIS) and thus yielding highly sensitive
      responses with a limit of detection (LOD) at the ppb level. Moreover, the sensor
      selectively responds to polar ethanol and acetone, as well as aromatic benzene,
      toluene, and chlorobenzene, but is insensitive to nonpolar ethane or hexane. The
      selectivity most likely arises from hydrogen bonding and dipole interaction of
      VOCs with silica surface.

PMID- 30101588
TI  - Isolation of Jahanene and Jahanane, and Total Synthesis of the Jahanyne Family.
AB  - Two new jahanyne analogues, jahanene and jahanane, highly N-methylated
      lipopeptides, were isolated from a marine cyanobacterium Okeania sp., and their
      structures were determined by NMR and MS. In addition, we achieved total
      syntheses of the jahanyne family and assessed their activities. The resulting
      growth-inhibitory activity of jahanyne was nearly one-tenth of the previously
      reported activity. Furthermore, we found that the degree of unsaturation at the
      terminus of the fatty acid moiety affected the growth-inhibitory activity against
      human cancer cells.

PMID- 30101590
TI  - Spectral Signatures of Proton-Transfer Dynamics at the Cusp of Low-Barrier
      Hydrogen Bonding.
AB  - Despite their importance in diverse chemical and biochemical processes, low
      barrier hydrogen bonds remain elusive targets to classify and interpret
      spectroscopically. Here the correlated nature of hydrogen bonding and proton
      transfer in the low-barrier regime has been probed for the ground and excited
      electronic states of 6-hydroxy-2-formylfulvene by acquiring jet-cooled
      fluorescence spectra of the parent and monodeuterated isotopologs. While excited
      state profiles reveal regular vibronic patterns devoid of obvious dynamical
      signatures, their ground-state counterparts display a radically altered energy
      landscape characterized by spectral bifurcations comparable in magnitude to
      typical vibrational spacings (>100 cm-1). Quantitative analyses yield unusual
      deuterium kinetic isotope effects that straddle limiting values attributed to
      above-barrier vibration and below-barrier tunneling of the proton adjoining
      donor/acceptor sites. Our findings provide compelling experimental evidence for
      ultrafast hydron-migration events commensurate with the onset of low-barrier
      hydrogen bonding and afford a trenchant glimpse of molecular phenomena taking
      place at the "tipping point" between disparate dynamical regimes.

PMID- 30101591
TI  - Revisiting the Long-Range Perlin Effect in a Conformationally Constrained
      Oxocane.
AB  - Unusual 1 JCH values for an oxocane derivative were recently reported,
      highlighting the unexpected long-range Perlin effect for the 1 JCH. According to
      our theoretical and experimental results listed in this paper, the previous
      published data cannot be supported. Moreover, when comparing the previously
      studied oxocane derivative with analogous molecules, we realized that the
      difference between J-couplings actually comes from the increase in the 1 JC-Hax
      instead of decreasing of 1 JC-Heq, as suggested.

PMID- 30101592
TI  - One-Pot Synthesis of Structurally Diverse Iminosugar-Based Hybrid Molecules.
AB  - A one-pot iminium-ion-based strategy has been developed for the synthesis of
      structurally novel iminosugar-based hybrid molecules. Iminium ion derived from l
      rhamnose lactol-mesylate reacted with electron-rich aromatic systems in an
      inter/intra molecular fashion to furnish pyrrolidine-based iminosugar C-aryl
      glycosides with a high degree of stereoselectivity. Iminium ion also reacted
      readily with active methylene compounds such as 4-hydroxycoumarin, 4
      hydroxyquinolinone, and lawsone to provide iminosugar C
      coumarin/quinolinone/naphthoquinonyl glycosides in very good yields. Azomethine
      ylide generated from an iminium ion derivative underwent dipolar cycloaddition
      reaction with 1,4-quinones to furnish novel isopyrrolonaphtho/anthroquinon-based
      iminosugar-hybrids. The preliminary cytotoxic activities of some of the
      synthesized iminosugar-hybrids have been assayed against various human cancer
      cell lines and some of the hybrid molecules exhibited promising anticancer
      activities.

PMID- 30101593
TI  - Analysis of alternative splicing in chicken embryo fibroblasts in response to
      reticuloendotheliosis virus infection.
AB  - Alternative splicing (AS) plays a significant role in regulation of genomic
      expression at the transcriptional level and is involved in many important
      biological functions of cells, thus a gene can be spliced into distinct
      transcript variants then translated to many different kinds of protein.
      Reticuloendotheliosis virus (REV) is a kind of retrovirus that can infect
      multiple avian species, leading to runting syndrome, immunosuppression and
      oncogenesis. In this present study, we analyzed AS in REV-infected chicken embryo
      fibroblasts (CEFs) which were inoculated with the second generation of REV (group
      VB) and compared with normal CEFs (group C) by high-throughput RNA sequencing
      technology. A total of 6,939 genes which were alternatively spliced were
      detected, among them, skipped exon (SE) was the most common pattern. Moreover,
      5,607 AS genes were detected as differentially expressed; compared with group C,
      group VB has 2,825 genes upregulated significantly and 2,782 genes downregulated
      significantly. These 5,607 differentially expressed AS genes are involved in many
      important biological processes. Many of them are involved in apoptosis and
      tumourigenesis. We also proved, by agarose gel electrophoresis, that AS events
      predicted by our study are authentic and AS is closely related with apoptosis and
      tumourigenesis in REV-infected CEFs. Our study provides the best analysis to date
      of the potential link between AS and CEFs in response to REV infection. Research
      highlights Transcriptomics analysis of REV-infected CEFs using high-throughput
      sequencing. Potential link between alternative splicing and CEFs in response to
      REV infection. Skipped exon is the most common spliced pattern in REV-infected
      CEFs. Differentially expressed genes mainly involved in apoptosis and
      tumourigenesis.

PMID- 30101594
TI  - Object personification in autism: This paper will be very sad if you don't read
      it.
AB  - Object personification is the attribution of human characteristics to non-human
      agents. In online forums, autistic individuals commonly report experiencing this
      phenomenon. Given that approximately half of all autistic individuals experience
      difficulties identifying their own emotions, the suggestion that object
      personification may be a feature of autism seems almost paradoxical. Why would a
      person experience sympathy for objects, when they struggle to understand and
      verbalise the emotions of other people as well as their own? An online survey was
      used to assess tendency for personification in 87 autistic and 263 non-autistic
      adults. Together, our results indicate that object personification occurs
      commonly among autistic individuals, and perhaps more often (and later in life)
      than in the general population. Given that in many cases, autistic people report
      their personification experiences as distressing, it is important to consider the
      reasons for the increased personification and identify structures for support.

PMID- 30101595
TI  - Correspondence of Maximum and Typical Performance Measures of Cognitive
      Processing.
AB  - We examined associations among cognitive processing measures that varied on a
      continuum from maximum to typical performance tasks in the context of an ego
      depletion study. Our intent was to replicate and extend the findings of Charek,
      Meyer, and Mihura, which showed that ego depletion had an expected effect on
      selected scores from the Rorschach inkblot task. We hypothesized that Rorschach
      variables indicative of cognitive sophistication would correlate with
      neuropsychological measures of cognitive ability and that Rorschach variables
      theoretically unassociated with cognitive processing would not correlate with
      those criterion measures. These hypotheses were supported, providing evidence of
      convergent and discriminant validity. We also hypothesized ego depletion effects
      on all measures; however, none were evident. Methodological considerations and
      implications of the findings are discussed.

PMID- 30101596
TI  - Multiyear Performance Trends Analysis of Primary Care Practices Demonstrating
      Patient-Centered Medical Home Transformation: An Observation of Quality
      Improvement Indicators among Outpatient Clinics.
AB  - Despite the ever-changing requirements of modern policy, payers seek
      interventions for care delivery improvement through value-based care models.
      Prior research acknowledges the Patient-Centered Medical Home (PCMH) as a tool
      for performance and outcomes improvement. However, these studies lack empirical
      evidence of performance trends across medical homes. A retrospective
      observational study was conducted to describe national trends in National
      Committee for Quality Assurance PCMH recognition for more than 23 000 primary
      care practices across the United States from 2008 to 2017. More than half of
      recognized practices scored 100% pass rates for activities related to appointment
      availability, patient care planning, and data for population management. The most
      common underperforming PCMH activities were for practice team, referral tracking
      and follow-up, and quality improvement implementation. Study findings indicate
      that patient-centered care collaboration between clinical and nonclinical team
      members, primary care provider coordination with specialty care providers, and
      practice implementation of clinical quality improvement methodologies are
      particularly challenging activities.

PMID- 30101597
TI  - Prevalence of overweight and obesity among US youth with autism spectrum
      disorder.
AB  - The purpose of this study was to examine current overweight and obesity
      prevalence rates among US youth (aged 10-17 years) with and without autism
      spectrum disorder, based on the 2016 National Survey of Children's Health.
      Analyses of weight status, derived from parent-reported height and weight
      measures, were conducted for a weighted sample of 875,963 youth with autism
      spectrum disorder and 31,913,657 typically developing youth. Controlling for age,
      race/ethnicity, income, and sex, youth with autism spectrum disorder had
      significantly higher odds of overweight (odds ratio = 1.48, p = 0.04) and obesity
      (odds ratio = 1.49, p = 0.02) compared to typically developing youth. Among youth
      with autism spectrum disorder, 19.4% were overweight and 23.05% were obese. Among
      typically developing youth, 14.9% were overweight and 15.91% were obese. Higher
      odds of obesity were reported for youth with severe autism spectrum disorder
      (odds ratio = 3.35, p < 0.01), compared to those with mild autism spectrum
      disorder.

PMID- 30101598
TI  - Dr. Mathilde Krim: A Memorial Tribute.

PMID- 30101599
TI  - Which parents dropout from an evidence-based parenting programme (Triple-P) at
      CAMHS? Comparison of programme-completing and dropout parents.
AB  - Evidence-based parenting programmes are beneficial for children's behavioural and
      emotional problems as well as parenting practices. Along with effectiveness,
      attendance affects the programme outcome and identification of risks associated
      with dropout may aid in development of special policy to increase engagement. In
      this study, we aimed to compare sociodemographics, parental attitudes, child
      behavioural and emotional problems of programme-completing and dropout parents
      from Level-4 Triple-P parenting programme applied at Child and Adolescent Mental
      Health Services (CAMHS). We also aimed to determine the attrition rate. In
      addition, we inquired whether there was a change in parenting styles and child
      behaviour and emotional problems before and after Level-4 Triple-P for the
      programme-completing parents at CAMHS. Results displayed that 52% ( n = 58) of
      the parents who were significantly less educated, used hostile rejecting
      attitudes, and reported more hyperactive/inattentive behaviour in their children
      compared to the parents who competed the programme ( p = 0.022, p = 0.016, p =
      0.027, respectively) discontinued the programme. Parents who were able to
      complete the programme ( n = 54) reported a reduction in over-parenting and
      improvements in children's conduct problems along with overall stress levels
      before and after Triple-P ( p = 0.009, p = 0.040, p = 0.023). Parents at risk of
      discontinuing parenting programmes may require special policy to be engaged since
      these programmes may offer significant benefits for parenting practices and, in
      turn, children's well-being.

PMID- 30101600
TI  - Processing fluency effect of a leaflet for breast and cervical cancer screening:
      a randomized controlled study in Japan.
AB  - Processing fluency (the inferred subjective ease with which people process
      information) has been a topic of increasing research attention in the field of
      psychology over the past decade. We examined the effect of improving written
      materials in terms of processing fluency with regard to encouragement for
      obtaining breast and cervical cancer screening. We randomly assigned 670 women to
      intervention or control conditions; the 215 who mailed back distributed
      questionnaires were the study participants. A standard leaflet for cancer
      screening was mailed to the control group, while the materials mailed to the
      intervention group were improved in terms of perceptual fluency (e.g.,
      legibility), linguistic fluency (e.g., readability), retrieval fluency (e.g.,
      reducing amount of information) and imagery fluency (having recipients imagine
      future behavior and events). The screening rate of the intervention group was
      significantly higher than that of the control group (29.4% vs. 14.2%, chi2 =
      7.275, df = 1, p = .007, phi = .184). Improving the processing fluency of written
      materials may be useful for encouraging individuals to obtain breast and cervical
      cancer screening.

PMID- 30101601
TI  - Gender Dysphoria in looked-after and adopted young people in a gender identity
      development service.
AB  - This research investigated the prevalence of looked-after and adopted young
      people within a case file review of 185 young people referred to a UK gender
      identity development service over a 2-year period (1 April 2009 to 1 April 2011).
      Data were extracted from referral letters, clinical notes and clinician letters.
      Looked-after young people were found to represent 4.9% of referrals in this
      cohort, which is significantly higher than within the English general population
      (0.58%). Adopted young people represented 3.8% of referrals. In addition, the
      findings showed that looked-after young people were less likely to receive a
      diagnosis of gender dysphoria compared with young people living within their
      birth family. There were no statistically significant differences in the gender
      ratio or age of first gender dysphoric experience between groups. Looked-after
      and adopted young people were also not found to be experiencing greater
      impairment in overall functioning compared to other young people referred to the
      gender identity development service. In conclusion, there are a substantial
      proportion of referrals pertaining to looked-after or adopted young people, and
      it appears the referral route and process through the service may be distinct,
      particularly for looked-after young people. This may be understood by considering
      the possible complexities in the presentation of these groups, alongside the
      established higher levels of complexity generally for those experiencing feelings
      of gender dysphoria.

PMID- 30101602
TI  - Unmasking the Practices of Nurses and Intercultural Health in Sub-Saharan Africa:
      A Useful Way to Improve Health Care?
AB  - In 2001 and 2013, the World Health Organization (WHO) published the WHO
      Traditional Medicine Strategy 2002-2005 and 2014-2023, respectively, to address
      policy, ethics, quality, and integration of complementary health therapies (CHT).
      Despite the adoption of these strategic frameworks, sub-Saharan African (SSA)
      countries largely run dualistic and inclusive health care system. A recent
      article published in Complementary Therapies in Clinical Practice analyzed the
      role of practicing nurses in CHT integration and intercultural health in an SSA
      country setting. Drawing on the Complementary and Alternative Medicine Health
      Belief Questionnaire, the study specifically examined nurses' knowledge,
      practices, and attitudes toward CHT. The study revealed that nurses had low
      knowledge about CHT, which reflected in their ineptitude to engage in
      professional practices of CHT. In spite of the knowledge deficit, nurses
      generally held favorable attitudes toward CHT and the majority supported the need
      for "safe" and evidence-based integrative model. Efforts to improve CHT-related
      knowledge of nurses may enhance medical integration in SSA. This commentary
      proposes novel political will and investment in CHT education and research as
      well as an inclusion of CHT modules in the nurses' training programs; viabilities
      to achieve intercultural health and improved care in SSA.

PMID- 30101603
TI  - Psychological distress in patients with obstructive sleep apnoea: The role of
      hostility and coping self-efficacy.
AB  - We aimed to assess whether hostility and coping self-efficacy are associated with
      psychological distress in obstructive sleep apnoea patients. Furthermore, we
      examined whether coping self-efficacy mediates the association between hostility
      and psychological distress. We included 150 obstructive sleep apnoea patients
      (Apnoea-Hypopnoea Index ?5; 68% male; mean age: 48.9 +/- 9.5 years). Regression
      models showed that hostility and poor coping self-efficacy were strongly
      associated with psychological distress in obstructive sleep apnoea patients. All
      assessed coping self-efficacy dimensions mediated the association between
      hostility and psychological distress. Coping self-efficacy for stopping
      unpleasant emotions and thoughts showed the strongest association with a lower
      level of psychological distress.

PMID- 30101604
TI  - Inhibition of MicroRNA-9-5p Protects Against Cardiac Remodeling Following
      Myocardial Infarction in Mice.
AB  - Follistatin-like 1 (Fstl1) protects cardiomyocytes from a broad spectrum of
      pathologic injuries including myocardial infarction (MI). It is worthy of note
      that although cardiac Fstl1 is elevated in post-MI microenvironment, its
      cardioprotective role is still restricted to a limited extent considering the
      frequency and severity of adverse cardiac remodeling following MI. We therefore
      propose that intrinsic Fstl1-suppressing microRNA (miRNA) may exist in the heart
      and its neutralization may further facilitate post-MI recovery. Here, miR-9-5p is
      predicted as one of the potential Fstl1-targeting miRNAs whose expression is
      decreased in ischemic myocardium and reversely correlated with Fstl1. Luciferase
      activity assay further validated Fstl1 as a direct target of miR-9-5p. In
      addition, forced expression of miR-9-5p in H9c2 cells is concurrent with
      diminished expression of Fstl1 and vice versa. Importantly, transfection of miR-9
      5p mimics in hypoxic H9c2 cells exacerbates cardiac cell death, lactate
      dehydrogenase release, reactive oxygen species accumulation, and
      malonyldialdehyde concentration. More importantly, in vivo silencing of miR-9-5p
      by a specific antagomir in a murine acute MI model effectively preserves post-MI
      heart function with attenuated fibrosis and inflammatory response. Further
      studies demonstrated that antagomir treatment stabilizes Fstl1 expression as well
      as blocks cardiac cell death and reactive oxygen species generation in both
      ischemia-challenged hearts and hypoxia-treated cardiomyoblasts. Finally,
      cytoprotection against hypoxic challenge by miR-9-5p inhibitor is partially
      reversed by knockdown of Fstl1, indicating a novel role of miR-9-5p/Fstl1 axis in
      survival defense against hypoxic challenge. In summary, these findings identified
      miR-9-5p as a mediator of hypoxic injury in cardiomyoblasts and miR-9-5p
      suppression prevents cardiac remodeling after acute MI, providing a potential
      strategy for early treatment against MI.

PMID- 30101605
TI  - A History of the Mind and Mental Health in Classical Greek Medical Thought.
AB  - This book on ancient medicine offers a unique resource for historians of
      medicine, historians of psychology, and classicists - and also cultural
      historians and historians of art. The Hippocratic texts and other contemporary
      medical sources have often been overlooked when it comes to their approaches to
      psychology, which are considered more mechanical and less elaborated than
      contemporary poetic and philosophical representations, but also than later
      medical works, notably Galenic. This book aims to do justice to early medical
      accounts by illustrating their richness and sophistication, their links with
      contemporary cultural products, and the indebtedness of later medicine to their
      observations. The ancient sources are read not only as archaeological documents,
      but also in the light of methodological discussions that are fundamental in the
      history of psychiatry and the history of psychology.

PMID- 30101606
TI  - Creating a new psychiatry: on the origins of non-institutional psychiatry in the
      USA, 1900-50.
AB  - This paper examines the early origins of the shift away from institutional
      psychiatry in the USA. It focuses on the period between 1900 and 1950. Attention
      is paid to the role of neurologists and disaffected asylum doctors in the early
      emergence of extra-institutional practice; to the impact of the National
      Committee for Mental Hygiene and Thomas Salmon; to the limited role of
      psychoanalysis during most of this period; and to the influence of the
      Rockefeller Foundation's decision to focus most of its effort in the medical
      sciences on psychiatry.

PMID- 30101607
TI  - Artificial intelligence in drug discovery.

PMID- 30101608
TI  - Gene Therapy Rescues Retinal Degeneration in Receptor Expression-Enhancing
      Protein 6 Mutant Mice.
AB  - Hereditary retinal dystrophy is clinically defined as a broad group of chronic
      and progressive disorders that affect visual function by causing photoreceptor
      degeneration. Previously, we identified mutations in the gene encoding receptor
      expression-enhancing protein 6 (REEP6), in individuals with autosomal recessive
      retinitis pigmentosa (RP), the most common form of inherited retinal dystrophy.
      One individual was molecularly diagnosed with biallelic REEP6 mutations, a
      missense mutation over a frameshift mutation. In this study, we generated Reep6
      compound heterozygous mice, Reep6L135P/-, which mimic the patient genotype and
      recapitulate the early-onset retinal degeneration phenotypes observed in the
      individual with RP. To determine the feasibility of rescuing the Reep6 mutant
      phenotype via gene replacement therapy, we delivered Reep6.1, the mouse retina
      specific isoform of REEP6, to photoreceptors of Reep6 mutant mice on postnatal
      day 20. Evaluation of the therapeutic effects 2 months posttreatment showed
      improvements in the photoresponse as well as preservation of photoreceptor cells.
      Importantly, guanylyl cyclase 1 (GC1) expression was also restored to the outer
      segment after treatment. Furthermore, rAAV8-Reep6.1 single treatment in Reep6
      mutant mice 1 year postinjection showed significant improvements in retinal
      function and morphology, suggesting that the treatment is effective even after a
      prolonged period. Findings from this study show that gene replacement therapy in
      the retina with rAAV overexpressing Reep6 is effective, preserving photoreceptor
      function in Reep6 mutant mice. These findings provide evidence that rAAV8-based
      gene therapy can prolong survival of photoreceptors in vivo and can be
      potentially used as a therapeutic modality for treatment of patients with RP.

PMID- 30101609
TI  - The effect of body dissatisfaction on disordered eating: The mediating role of
      self-esteem and negative affect in male and female adolescents.
AB  - This study aimed to determine whether self-esteem and negative affect
      sequentially mediate the relationship between body dissatisfaction and disordered
      eating. A total of 806 adolescents (61.8% females) completed the Drive for
      Thinness, Bulimia, and Body Dissatisfaction subscales of the Eating Disorder
      Inventory-2, the Anxiety and Depression subscales of the General Health
      Questionnaire-28, and the Negative Self-beliefs subscale of the Eating Disorder
      Belief Questionnaire. Mediational analyses showed that body dissatisfaction had
      both direct and indirect effects through self-esteem and negative affect on
      disordered eating. It was also observed that negative self-esteem mediated
      completely in boys and partially in girls-the relationship between body
      dissatisfaction and negative affect.

PMID- 30101610
TI  - Investigating the Association Between Diabetes Distress and Self-Management
      Behaviors.
AB  - BACKGROUND:: Diabetes distress has been linked with suboptimal glycemic control
      in patients with type 1 diabetes. We evaluated the effect of diabetes distress on
      self-management behaviors in patients using insulin pumps. METHODS:: We analyzed
      the impact of diabetes distress on self-management behaviors using pump downloads
      from 129 adults treated with continuous subcutaneous insulin infusion (CSII) at a
      single hospital clinic. Exclusion criteria were CSII treatment <6 months,
      pregnancy, hemoglobinopathy, and continuous glucose monitoring/sensor use. People
      were categorized into three groups based on the Diabetes Distress Scale-2 (DDS-2)
      score: < 2.5, 2.5-3.9, > 4. RESULTS:: Participants had a mean age of 45.2 +/-
      19.0 years; duration of diabetes 26.6 +/- 16.2 years; duration of CSII 6.0 +/-
      3.5 years; HbA1c 8.0 +/- 1.2%; and DDS-2 score 2.7 +/- 1.3. Self-monitoring blood
      glucose (SMBG) frequency and bolus wizard usage was similar between groups.
      Patients with higher distress had higher HbA1c (7.7 +/- 0.9 vs. 8.0 +/- 0.9 vs.
      8.7 +/- 1.8; P = 0.004), lower frequency of set changes (4.7 +/- 1.3vs. 4.8 +/-
      1.9 vs. 3.8 +/- 1.1; P = .025), a greater number of appointments booked (5.8 +/-
      4.4 vs. 8.6 +/- 4.8 vs. 8.1 +/- 6.9; P = .021), and a greater number of
      appointments missed (1.9 +/- 1.3 vs. 2.5 +/- 1.5 vs. 3.8 +/- 4.1; P = .004).
      CONCLUSIONS:: Although in some patients, high distress may be caused by reduced
      self-management, in our highly trained, pump-using patients, high distress was
      associated with suboptimal biomedical outcomes despite appropriate self
      management behaviors. Future work should further explore the relationships
      between diabetes distress, self-management, and glycemic control.

PMID- 30101611
TI  - Patient characteristics and bleeding events in nonvalvular atrial fibrillation
      patients treated with apixaban or vitamin K antagonists: real-world evidence from
      Italian administrative databases.
AB  - AIM: This study aimed to evaluate the risk of major bleeding among two cohorts of
      nonvalvular atrial fibrillation patients newly initiating a vitamin K antagonist
      (VKA) or apixaban in a real-world setting in Italy. PATIENTS & METHODS: A
      retrospective study using a large administrative database of Italian local health
      units was performed, using data from ten local health units and patients were
      included from the date of new initiation of apixaban or VKAs from January 2012 to
      June 2015. RESULTS: Risk of major bleeding was calculated using an adjusted Cox
      regression model. Compared with VKA, apixaban had a significantly lower risk of
      major bleeding (hazard ratio = 0.44 [95% CI: 0.12-0.97]). CONCLUSION: In this
      analysis, apixaban was associated with a lower risk of major bleeding compared
      with VKA.

PMID- 30101612
TI  - Prognostic and predictive biomarkers in nonmetastatic colorectal cancers.

PMID- 30101613
TI  - Azithromycin or erythromycin? Macrolides for non-cystic fibrosis bronchiectasis
      in adults: A systematic review and adjusted indirect treatment comparison.
AB  - Non-cystic fibrosis (non-CF) bronchiectasis is a condition characterized by an
      airway inflammatory response to bacterial pathogens. Frequent exacerbations have
      a major influence on the quality of life. Macrolide antibiotics have not only
      antibacterial but also immune-regulation effects. It is proved that macrolides
      have a benefit in preventing exacerbations. However, it is still uncertain
      whether azithromycin or erythromycin is more effective and safe. The purpose of
      this study was to answer the following question: Which kind of macrolide
      antibiotic is more effective and safe in preventing non-CF bronchiectasis
      exacerbation? We conducted a systematic review to identify randomized clinical
      trials published up to May 2017 that reported on macrolides for non-CF
      bronchiectasis and an adjusted indirect treatment comparison (AITC) between
      macrolides to evaluate their efficacy and safety. The direct comparison meta
      analysis found that macrolides decreased the rate of exacerbation of non-CF
      bronchiectasis (risk ratio (RR) = 0.45; 95% confidence interval (CI) 0.36-0.55)
      with heterogeneity ( I2 = 63.7%, p = 0.064). The AITC showed that azithromycin
      had a significantly lower bronchiectasis exacerbation rate than erythromycin (RR
      = 0.35; 95% CI: 0.403-0.947). Azithromycin increased the risk of diarrhea and
      abnormal pain. This meta-analysis suggested that long-term treatment with
      macrolides significantly reduced the incidence of non-CF bronchiectasis
      exacerbation. Moreover, azithromycin is more efficient than roxithromycin and
      erythromycin in preventing exacerbation.

PMID- 30101614
TI  - Choroidal neovascularization due to choroidal osteoma treated with anti-vascular
      endothelial growth factor therapy: An optical coherence tomography angiography
      study.
AB  - PURPOSE: To evaluate the response to anti-vascular endothelial growth factor
      therapy for choroidal neovascularization secondary to choroidal osteoma using
      optical coherence tomography angiography. METHODS: This retrospective study
      included four eyes of four females with choroidal osteoma complicated by
      choroidal neovascularization, treated with ranibizumab. All patients underwent
      full ophthalmologic examination, including ocular ultrasound, retinography,
      fluorescein angiography, spectral-domain or swept-source optical coherence
      tomography, and optical coherence tomography angiography. These images were
      analyzed to measure choroidal osteoma and to study choroidal neovascularization
      changes after intravitreal anti-vascular endothelial growth factor. RESULTS: In
      all cases, fluorescein angiography revealed the presence the choroidal
      neovascularization, as an early hyperfluorescence area increasing during the
      exam. Optical coherence tomography showed both the choroidal osteoma and
      choroidal neovascularization and intra- or subretinal fluid as activity sign. In
      optical coherence tomography angiography, choroidal osteoma vessels were valuable
      in outer retina and choroidal slabs, and were irregular and did not change after
      ranibizumab injection; neovascular network correlating with choroidal
      neovascularization showed a hyperflow tangled vessels in outer retina, decreasing
      in density after anti-vascular endothelial growth factor therapy. CONCLUSION:
      Optical coherence tomography angiography seems to be a useful tool in visualizing
      and distinguishing vascular networks of choroidal osteoma and of choroidal
      neovascularization secondary to choroidal osteoma better than fluorescein
      angiography.

PMID- 30101616
TI  - Revisiting isotonic phase I design in the era of model-assisted dose-finding.
AB  - Background/aims In the conduct of phase I trials, the limited use of innovative
      model-based designs in practice has led to an introduction of a class of "model
      assisted" designs with the aim of effectively balancing the trade-off between
      design simplicity and performance. Prior to the recent surge of these designs,
      methods that allocated patients to doses based on isotonic toxicity probability
      estimates were proposed. Like model-assisted methods, isotonic designs allow
      investigators to avoid difficulties associated with pre-trial parametric
      specifications of model-based designs. The aim of this work is to take a fresh
      look at an isotonic design in light of the current landscape of model-assisted
      methods. Methods The isotonic phase I method of Conaway, Dunbar, and Peddada was
      proposed in 2004 and has been regarded primarily as a design for dose-finding in
      drug combinations. It has largely been overlooked in the single-agent setting.
      Given its strong simulation performance in application to more complex dose
      finding problems, such as drug combinations and patient heterogeneity, as well as
      the recent development of user-friendly software to accompany the method, we take
      a fresh look at this design and compare it to a current model-assisted method. We
      generated operating characteristics of the Conaway-Dunbar-Peddada method using a
      new web application developed for simulating and implementing the design and
      compared it to the recently proposed Keyboard design that is based on toxicity
      probability intervals. Results The Conaway-Dunbar-Peddada method has better
      performance in terms of accuracy of dose recommendation and safety in patient
      allocation in 17 of 20 scenarios considered. The Conaway-Dunbar-Peddada method
      also allocated fewer patients to doses above the maximum tolerated dose than the
      Keyboard method in many of scenarios studied. Overall, the performance of the
      Conaway-Dunbar-Peddada method is strong when compared to the Keyboard method,
      making it a viable simple alternative to the model-assisted methods developed in
      recent years. Conclusion The Conaway-Dunbar-Peddada method does not rely on the
      specification and fitting of a parametric model for the entire dose-toxicity
      curve to estimate toxicity probabilities as other model-based designs do. It
      relies on a similar set of pre-trial specifications to toxicity probability
      interval-based methods, yet unlike model-assisted methods, it is able to borrow
      information across all dose levels, increasing its efficiency. We hope this
      concise study of the Conaway-Dunbar-Peddada method, and the availability of user
      friendly software, will augment its use in practice.

PMID- 30101615
TI  - Recruitment and retention of the Hardest-to-Reach families in community-based
      asthma interventions.
AB  - BACKGROUND/AIMS: Engaging underserved populations in research requires
      substantial effort for recruitment and retention. The objective of this study is
      to describe the effort needed to recruit and retain urban participants in
      pediatric asthma studies and to characterize the Hardest-to-Reach group by
      demographics and asthma severity. METHODS: We included 311 children (3-10 years)
      with persistent asthma enrolled in two school-based asthma interventions in
      Rochester, NY. Contact logs were collected at four time points (baseline, 2
      month, 4 month, 6 month). We defined "Hardest-to-Reach" (vs "Easier-to-Reach") as
      being unable to reach a family by telephone at any given contact attempt due to
      disconnected or wrong numbers. Chi-square and Mann-Whitney tests were used to
      compare groups. RESULTS: Overall, we enrolled 311 children (60% Black, 29%
      Hispanic, 70% Medicaid, response rate 70%). On average, 3.1 contact attempts were
      required for recruitment (range 1-15), and 35% required rescheduling at least
      once for the enrollment visit. All but 12 participants completed each follow-up
      (retention rate = 96%). Completion of follow-ups required an average of 7.6
      attempts; we considered 38% of caregivers "Hardest-to-Reach." Caregivers in the
      Hardest-to-Reach group were slightly younger (33 vs 36 years, p = 0.007) with
      more depressive symptoms (41% vs 29%, p = 0.035) and smokers in the home (59% vs
      48%, p = 0.048). Furthermore, more of the Hardest-to-Reach children had moderate
      severe versus mild persistent asthma (64% vs 52%, p = 0.045). Importantly, even
      the Easier-to-Reach families required many contact attempts, with 52% having >5
      attempts for at least one follow-up. CONCLUSION: In conclusion, we found that
      among an already vulnerable population, the Hardest-to-Reach families
      demonstrated higher risk and had children with significantly worse asthma. This
      study highlights the importance of persistence in reaching those in greatest
      need.

PMID- 30101618
TI  - Referral for first glaucoma surgery in Europe, the ReF-GS study.
AB  - PURPOSE: To analyze the appropriateness of referrals for incisional glaucoma
      surgery in Europe. METHODS: Referrals for the first open-angle glaucoma surgery
      between January and October 2017 were analyzed in 18 countries: 8 "old" European
      Union, 7 "new" European Union and 3 non-European Union European countries.
      RESULTS: Most eyes had primary open-angle or exfoliative glaucoma. The average
      mean deviation was -13.8 dB with split fixation in 44.3%. No structural
      progression analysis was made before the referrals. The most common medications
      were the combination of a prostaglandin analog, timolol and a carbonic anhydrase
      inhibitor (30.0%), and all other combinations comprising ? 3 molecules (33.8%).
      Laser trabeculoplasty was reported in only 18.4%. Of the 294 referrals, 41.5%
      were appropriate and timely, 35.0% appropriate but later than optimal, and 17.6%
      appropriate but too late (minimal vision maintained). The treatment period was
      significantly longer (median: 7 years) in the "old" European Union countries than
      in the other groups (3 and 2 years, respectively). No between-group differences
      were seen in intraocular pressure and mean deviation, but the non-European Union
      group referred the patients at significantly lower cup/disk ratio and eye drop
      usage than the other groups. Split fixation was significantly more common in the
      "old" (60.6%) than the "new" European Union countries (38.7%), and in both EU
      country-groups than in the non-European Union countries (13.6%). CONCLUSIONS: Of
      294 European open-angle glaucoma referrals for first glaucoma-surgery, 41.5% were
      completely satisfactory. The damage was typically advanced, and the care varied
      considerably among the countries. This suggests that further efforts are
      necessary to improve glaucoma care in Europe.

PMID- 30101617
TI  - Role of Organizational Climate in Job Involvement: A Way to Develop the
      Organizational Commitment of Nursing Staff.
AB  - Employees are the most valuable assets of an organization; therefore, it is very
      important to understand their behavior. In this regard, the present study was
      carried out in order to examine the effect of organizational climate on job
      involvement among nurses working in the teaching hospitals of Qazvin Province,
      Iran. The present descriptive analytical study was done in 2017. To randomly
      select a specific proportion of nurses from each of Qazvin teaching hospitals,
      stratified sampling was used. In total, 340 nurses were selected. Data were
      collected using 3 questionnaires: Halpin and Kraft Organizational Climate
      Questionnaire, Job Involvement Questionnaire (Kanungo), and Allen and Myer
      Organizational Commitment Questionnaire. For data analysis, confirmatory factor
      analysis and structural equation modeling were used applying AMOS-24 software.
      The results of path analysis showed the effect of organizational climate on the
      nurses' job involvement. Moreover, organizational climate influenced
      organizational commitment through the mediation of job involvement. According to
      values obtained for degree of freedom based on chi-square, goodness-of-fit index,
      root mean square error of approximation, and comparative fit index were in the
      defined range; therefore, the validity of the conceptual model was approved.
      Based on the results of the present study, managers of health organizations can
      achieve their goals by understanding the organizational climate of the hospitals
      and its effect on the employees' job involvement and discovering strategies
      needed for organizational commitment improvement.

PMID- 30101619
TI  - Increased risk for major depressive disorder in severely obese patients after
      bariatric surgery - a 12-year nationwide cohort study.
AB  - BACKGROUND: Bariatric surgery is associated with a significant improvement in
      depressive mood in the initial postoperative years, but the maintenance of the
      improvement is under debate. AIM: To explore the association between bariatric
      surgery and major depressive disorder (MDD) in a 12-year nationwide cohort study.
      METHOD: Using the National Health Insurance Research Database of Taiwan, we
      identified 2302 patients who underwent bariatric surgery in 2001-2009. These
      patients were matched by propensity score to 6493 obese patients who did not
      receive bariatric surgery. We followed the surgical and control cohorts until
      death, any diagnosis of MDD or 31 December 2012. We used Cox proportional hazard
      regression models to calculate the relative risk of MDD in those who received
      bariatric surgery. RESULTS: Overall, there was a 1.70-fold (95% CI: 1.27-2.27)
      higher risk of MDD in the surgical group. Subjects receiving malabsorptive
      procedures showed a higher risk of MDD (3.01, 95% CI: 1.78-5.09) than those
      receiving restrictive procedures (1.51, 95% CI: 1.10-2.07). Stratified by follow
      up period, there was a higher risk of MDD in the surgical group (2.92, 95% CI:
      1.75-4.88) than in the restrictive group four years after bariatric surgery.
      CONCLUSIONS: Bariatric surgery was significantly associated with an elevated risk
      of MDD. KEY MESSAGES Bariatric surgery is associated with a significant
      improvement in depressive mood in the initial postoperative years, but the
      improvement is not maintained. Less is known about the relationship between
      bariatric surgery and risk of major depressive disorder. This was the first
      nationwide cohort study which found that bariatric surgery was significantly
      associated with an elevated risk of MDD (aHR: 1.70; CI: 1.27-2.27), mainly with
      malabsorptive procedures (aHR: 3.01; CI: 1.78-5.09) and at time points more than
      four years after surgery (aHR: 2.92; CI: 1.75-4.88) compared with the risk in
      matched controls. These findings imply an association between long-term
      malabsorption and the postoperative incidence of MDD. Long-term malabsorption
      might be related to the incidence of major depressive disorder after bariatric
      surgery. The possible causal relationship between nutritional deficiency after
      bariatric surgery and major depressive disorder warrants further investigation.

PMID- 30101620
TI  - Evaluating Nonintegrating Lentiviruses as Safe Vectors for Noninvasive Reporter
      Based Molecular Imaging of Multipotent Mesenchymal Stem Cells.
AB  - Reporter gene-based molecular imaging can provide invaluable information on the
      fate of cellular therapies postimplantation. Integrating lentiviral vectors
      (ILVs) are commonly used for stably engineering cells; however, their potential
      for insertional mutagenesis poses a significant safety concern and barrier to
      widespread clinical adoption. In cells that slowly divide or are postmitotic in
      vivo, such as mesenchymal stem cells (MSCs), nonintegrating lentiviral vectors
      (NILVs) may be a safer alternative option because NILVs remain episomal and can
      provide prolonged expression profiles. Here, NILVs coexpressing fluorescence and
      bioluminescence imaging (BLI) reporters were engineered and used to
      longitudinally image the viability of human MSCs in vitro and in vivo in mice. In
      vitro, ILV-transduced cancer cells and MSCs maintained steady reporter gene
      expression over time, whereas NILV-transduced cells progressively lost signal.
      NILV reporter loss was accelerated in highly proliferative cancer cells compared
      with less proliferative MSCs. In vivo, ILV- and NILV-transduced MSCs were each
      detectable with BLI postintramuscular implantation, with significantly higher ILV
      based signal compared with NILV-based signal. BLI signal was observed to
      similarly diminish over time for both cell populations, which was attributed to
      cell death. Despite the reduced signal intensity with NILVs and the minimal
      number of cells injected (40,000), live NILV-transduced MSCs were reliably
      visualized for up to 2 weeks. Safety is a concern for future clinical reporter
      gene applications. We present NILVs as a safe means of imaging reporter gene
      expression for slowly dividing or nondividing cells and showed effective tracking
      of the viability of a small number of live transplanted MSCs over time with
      optical imaging. Future work will evaluate improvements to episomal NILV reporter
      expression, explore sensitive clinically relevant reporters, and apply this
      approach to clinically relevant MSC applications in preclinical models. NILVs may
      have broad clinical applications for expression of imaging reporters and other
      gene products in MSC-based therapies.

PMID- 30101621
TI  - Local strategies and delivery systems for the treatment of malignant gliomas.
AB  - Glioma is one of the most common type of malignant tumours with high morbidity
      and mortality rates. Due to the particular features of the brain, such as blood
      brain barrier or blood-tumour barrier, therapeutic agents are ineffective by
      systemic administration. The tumour inevitably recurs and devitalises patients.
      Herein, an overview of the localised gliomas treatment strategies is provided,
      including direct intratumoural/intracerebral injection, convection-enhanced
      delivery, and the implant of biodegradable polymer systems. The advantages and
      disadvantages of each therapy are discussed. Subsequently, we have reviewed the
      recent developments of therapeutic delivery systems aimed at transporting
      sufficient amounts of antineoplastic drugs into the brain tumour sites while
      minimising the potential side effects. To treat gliomas, localised and controlled
      delivery of drugs at their desired site of action is preferred as it reduces
      toxicity and increases treatment efficiency. Simultaneously, various drug
      delivery systems (DDS) have been used to enhance drug delivery to the brain. Use
      of non-conventional DDS for localised therapy has greatly expanded the spectrum
      of drugs available for the treatment of malignant tumours. Use smart DDS via
      localised delivery strategies, in combination with radiotherapy and multiple drug
      loading would serve as a promising approach to treat gliomas.

PMID- 30101622
TI  - 3,3'-Diindolylmethane ameliorates renal fibrosis through the inhibition of renal
      fibroblast activation in vivo and in vitro.
AB  - 3,3'-Diindolylmethane (DIM), a natural acid condensation extracted from
      cruciferous plants, exhibits anti-fibrotic effects in hepatic and cardiac
      fibrosis models. The effects of DIM on renal fibrosis, however, are unclear. This
      study aimed to explore the protective effects of DIM on renal fibrosis.
      Unilateral ureteral obstruction (UUO) and transforming growth factor (TGF)-beta1
      stimulated normal rat kidney (NRK)-49F fibroblast cell mouse models were
      established. The models were then treated with DIM for the assessment of its anti
      fibrotic effects and mechanisms. Results of HE and Masson staining showed that
      DIM reduced kidney injury and production of interstitial collagens fibrosis. CTS
      also inhibited expression of fibronectin, collagen-1 but retain E-cadherin in the
      UUO model. Furthermore, DIM suppressed local fibroblast activation, as evidenced
      by the suppressed expression of the myofibroblast markers alpha-SMA and vimentin
      in vivo and in vitro. In addition, DIM significantly inhibited the TGF-beta1
      induced proliferation of NRK49F cells in a time- and dose-dependent manner. DIM
      decreased Smad2/3 phosphorylation but increased Smad7 expression. Results
      suggested that DIM inhibits TGF-beta/Smad2/3 signaling to attenuate renal
      interstitial fibrosis via inhibiting local fibroblast activation. This mechanism
      is likely related to Smad7 induction.

PMID- 30101623
TI  - The safety of beclomethasone dipropionate in the treatment of ulcerative colitis.
AB  - INTRODUCTION: Beclomethasone dipropionate (BDP) is a second-generation
      corticosteroid that uses novel drug technologies to ensure colonic targeting and
      potentially reducing systemic corticosteroid concentrations. It is approved for
      treatment of patients with mild-to-moderate ulcerative colitis (UC) who do not
      respond to mesalazine. The gut-selective mechanism of action has the potential to
      improve the safety profile of BDP compared with other conventional
      corticosteroids. Areas covered: We reviewed the mechanism of action, efficacy,
      and safety of BDP in the treatment of UC. The positioning of BDP in management
      algorithms is also discussed. Expert opinion: The highly selective mechanism of
      action of BDP restricts the steroid-related side effects. BDP is efficacious in
      the treatment of active UC. Topical formulation is the first choice in distal UC,
      while oral formulation is used in patients with an extensive involvement of the
      colon. The rates of adverse events (AE), serious AEs, and steroid-related side
      effects are similar to placebo and mesalamine and slightly inferior to
      traditional corticosteroids.

PMID- 30101624
TI  - Preoperative Use of Statins in Carotid Artery Stenting: A Systematic Review and
      Meta-analysis.
AB  - PURPOSE: To determine through meta-analysis whether administration of statins
      before carotid artery stenting (CAS) is associated with fewer periprocedural
      adverse events. METHODS: All randomized and observational English-language
      studies of periprocedural statin administration prior to CAS that reported the
      outcomes of interest (stroke, transient ischemic attack, myocardial infarction,
      and death at 30 days) were included in a random-effects meta-analysis. The I2
      statistic was used to assess heterogeneity. Meta-regression analysis was
      performed to determine whether an association of statin treatment with risk of
      outcome events was influenced by other trial-level baseline characteristics of
      statin-treated and untreated patients. RESULTS: Eleven studies comprising 4088
      patients were included. Patients who received statins prior to CAS had a
      significantly lower risk of stroke (OR 0.39, 95% CI 0.27 to 0.58, p<0.01; I2=0%)
      and death (OR 0.30, 95% CI 0.10 to 0.96, p=0.042; I2=0%). Statin use was not
      associated with a reduced risk of transient ischemic attack or myocardial
      infarction. In meta-regression analysis, other trial-level baseline
      characteristics had no significant influence on the association of statin
      treatment with death or stroke. CONCLUSION: Statin therapy prior to CAS is
      associated with decreased risk of perioperative stroke and death without any
      effect on the rates of transient ischemic attack or myocardial infarction.

PMID- 30101625
TI  - Technique to Facilitate Retrograde Puncture of Mid to Upper Calf Tibial Vessels.
AB  - PURPOSE: To describe a simple maneuver to facilitate the retrograde puncture of
      challenging tibial vessels in the lower leg. TECHNIQUE: Because of the depth of
      the tibial vessels at the mid to upper calf, especially in obese or muscular
      patients, a 7- or 9-cm, 21-G micropuncture needle is often needed to reach the
      artery. However, the low profile of the needle contributes to its flexibility and
      therefore the tendency to bend as it progresses through the deep tissues,
      hindering access to the target vessel. To overcome this obstacle, a 4- to 5-cm,
      18-G needle is initially placed pointing to the artery. The 21-G needle is
      advanced through it to the target site. This simple maneuver increases the
      support to the 21-G needle, preventing its bending and facilitating arterial
      puncture in the presence of calcified vessels. CONCLUSION: The telescoping needle
      technique may be considered as a bailout procedure in the retrograde tibial
      approach after failed attempts secondary to needle bending or calcified vessels.

PMID- 30101626
TI  - Efficacy and toxicity of eribulin treatment in metastatic breast cancer patients.

PMID- 30101627
TI  - Catheter ablation for atrial fibrillation: current patient selection and
      outcomes.
AB  - INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia.
      Ablation is an excellent treatment option for appropriately selected patients.
      Catheter ablation tools and techniques have evolved since AF ablation was first
      introduced, but pulmonary vein isolation remains the cornerstone of the
      procedure. Outcomes from ablation have improved dramatically over the last 20
      years, but remain less than optimal for certain patient groups. Areas covered:
      This review outlines the process of patient selection for AF ablation in
      contemporary practice, from diagnosis and AF classification to procedural risk
      assessment. Current guideline indications for AF ablation are reviewed. We
      discuss current reported outcomes from AF ablation and predictors for arrhythmia
      recurrence after ablation. The evolution of AF ablation technology and change in
      patient selection patterns are also discussed. Expert commentary: AF ablation is
      an attractive alternative to antiarrhythmic drug therapy for many patients.
      Patient selection for ablation is an important part of management. Careful
      patient selection requires thorough, individualized clinical assessment based on
      symptoms, alternative treatment options, an estimation of procedural risk, and
      predicted recurrence rate to allow the patient to participate in shared decision
      making.

PMID- 30101628
TI  - Paeonol exhibits anti-tumor effects by apoptotic and anti-inflammatory activities
      in 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis.
AB  - We investigated the preventive potential of paeonol on 7,12
      dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. Oral tumors were
      developed in the buccal pouches of Syrian golden hamsters using topical
      application of 0.5% DMBA three times/week for 10 weeks. DMBA treated hamsters
      developed hyperplasia, dysplasia and well-differentiated squamous cell carcinoma.
      The animals also exhibited increased lipid oxidation, decreased antioxidant
      status and altered levels of detoxification agents. Paeonol treatment of DMBA
      treated hamsters for 14 weeks decreased tumor incidence, volume and burden
      Paeonol treatment also increased antioxidant activity and decreased lipid
      oxidation to near normal levels. Histomorphology and the expression patterns of
      mutant p53, cyclo-oxygenase (COX-2) and caspase-9 were investigated in the oral
      buccal mucosa. Paeonol exhibited protective effects against DMBA induced oral
      carcinogenesis owing to its antitumor, antioxidant, anti-inflammatory and
      apoptosis inducing properties.

PMID- 30101629
TI  - Carcinosarcoma of the prostate: case report with molecular and histological
      characterization.
AB  - BACKGROUND:: We report a case of prostatic carcinosarcoma, a rare variant of
      prostatic cancer, which is composed of a mixture of epithelial and mesenchymal
      components with a generally poor outcome. AIMS AND METHODS:: We aim to identify
      molecular alterations, in particular copy number variations of AR and c -MYC
      genes, methylation and expression of glutathione S-transferase P1 (GSTP1),
      programmed death-ligand 1 (PD-L1), AR, and phosphorylated AR expression.
      RESULTS:: We found a distinct molecular pattern between adenocarcinoma and
      carcinosarcoma, which was characterized by high AR copy number variation gain;
      positive expression of PD-L1, AR, and phosphorylated AR; low espression of GSTP1
      in epithelial component. The sarcomatoid component had a lower gain of the AR
      gene, and no expression of PD-L1, AR, phosphorylated AR, or GSTP1. Both
      components had a gain of c-MYC copy number variation. CONCLUSIONS:: Our findings
      suggest that carcinosarcoma has specific molecular characteristics that could be
      indicative for early diagnosis and treatment selection.

PMID- 30101631
TI  - Antineoplastic treatment with crizotinib during pregnancy: a case report.

PMID- 30101630
TI  - The challenge of avoiding intubation in immunocompromised patients with acute
      respiratory failure.
AB  - INTRODUCTION: A growing number of immunocompromised (IC) patients with acute
      hypoxemic respiratory failure (ARF) is admitted to the intensive care unit (ICU)
      worldwide. Areas covered: This review provides an overview of the current
      knowledge of the ways to prevent intubation in IC patients with ARF. Expert
      commentary: Striking differences oppose ARF incidence, characteristics,
      etiologies and management between IC and non-IC patients. Survival benefits have
      been reported with early admission to ICU in IC patients. Then, while managing
      hypoxemia and associated organ dysfunction, the identification of the cause of
      ARF will be guided by a rigorous clinical assessment at the bedside, further
      assisted by an invasive or noninvasive diagnostic strategy based on clinical
      probability for each etiology. Finally, the initial respiratory support aims to
      avoid mechanical ventilation for the many yet recognizing those patients for whom
      delaying intubation expose them to suboptimal management. We advocate for not
      using noninvasive ventilation (NIV) in this setting. A proper evaluation of High
      flow nasal cannula oxygen (HFNC)  is required in IC patients as to demonstrate
      its superiority compared to standard oxygen therapy. Day-to-day decisions must
      strive to avoid delayed intubation, and make every effort to identify ARF
      etiology.

PMID- 30101632
TI  - New anti-pseudomonal agents for cystic fibrosis- still needed in the era of small
      molecule CFTR modulators?
AB  - INTRODUCTION: Cystic fibrosis is characterized by bacterial lung infection, a
      majority of adults being chronically infected with Pseudomonas aeruginosa.
      Treatment is a major challenge, with frequent courses of antibiotics contributing
      to antimicrobial resistance. New approaches are clearly required. Over the last
      few years, a major shift in our approach to treating CF has occurred with the
      availability of the first drugs targeting the CFTR protein and leading to
      improvements in lung function, weight gain and frequency of exacerbations. Areas
      covered: There are emerging, but limited, data exploring the effect these drugs
      have on airway infections, some studies suggesting a beneficial impact. CFTR
      modulators probably possess very little direct antimicrobial activity, but both
      synergy with conventional antibiotics and alternative mechanisms of bacterial
      killing have been proposed. This article reviews the current published evidence.
      Expert opinion: The picture is far from clear concerning the impact of CFTR
      modulators on lung infections. However, currently, such drugs restore CFTR
      function incompletely, are most commonly introduced when lung damage is already
      present, are not suitable for all CF patients and not reimbursed in some areas.
      Therefore, whatever their eventual anti-infective potential, we need to continue
      our search for effective anti-pseudomonal therapies for the foreseeable future.

PMID- 30101633
TI  - Infusion administration billing for vedolizumab and infliximab in inflammatory
      bowel disease.
AB  - AIMS: Increasing use of biologics has led to interest in treatment components
      with potential for cost savings. This study was aimed at comparing administration
      times and associated costs of infliximab and vedolizumab infusions for
      inflammatory bowel disease (IBD). MATERIALS AND METHODS: This study used claims
      data from the Symphony Health Integrated Dataverse to identify IBD patients using
      infliximab or vedolizumab between 20 May 2014 and 29 February 2016. Use of
      Current Procedural Terminology administration codes was evaluated and costs
      calculated using the 2016 Center for Medicare and Medicaid Services Physician Fee
      Schedule. Assessments included infusion times, associated costs, productivity
      loss using average wage estimates from the United States Bureau of Labor
      Statistics, and home infusion adoption. RESULTS: A total of 10,051 infliximab and
      3114 vedolizumab patients with first-hour claims were identified; 52.0% were
      female and 64.5% had Crohn's disease. There were 48,377 infliximab first-hour
      claims (mean 4.8 infusions per patient); 46,462 (96.0%) had a second-hour claim.
      In comparison, there were 14,717 vedolizumab claims (mean 4.7 infusions per
      patient), with only 411 (2.8%) second-hour claims, resulting in vedolizumab cost
      savings of approximately $1.27 million. The difference in second-hour infusions
      resulted in 46,051 additional hours of productivity loss with infliximab, and
      lost wages averaging $1.18 million (range $0.68-$1.77 million). LIMITATIONS:
      Administration costs were inferred as charge costs and not directly assessed.
      Productivity loss assessed time spent on infusion only, and included a small
      proportion of patients beyond working age. CONCLUSIONS: Second-hour infusion
      billing was significantly lower with vedolizumab than with infliximab,
      corresponding to cost savings and reduced productivity loss.

PMID- 30101635
TI  - Acute pancreatitis secondary to the use of the anabolic steroid trenbolone
      acetate.
AB  - BACKGROUND: The use of performance-enhancing drugs has increased dramatically in
      the last decade with high prevalence reported among the young athlete population.
      Many of these drugs contain anabolic steroids and may carry potential significant
      side effects and health risks. We report a case of anabolic steroid-induced acute
      pancreatitis (AP) that recurred after the reuse of the same drug by the patient,
      confirming the causative relationship. CASE REPORT: A 24 year-old male presented
      with severe epigastric pain. His past medical history was significant for two
      hospitalizations during the last year with AP. During his hospital admissions,
      extensive workup was performed ruling out the common and uncommon causes of AP.
      Upon further pressing, the patient admitted to a history of past and current
      anabolic steroid use for athletic performance enhancement. He began this use four
      years ago and most recently started using trenbolone acetate (TA). The
      correlation between the timing of the anabolic steroids administration and the
      attacks of AP, along with ruling out other causes, confirmed TA as the cause of
      pancreatitis. DISCUSSION: The side effects associated with the use of these
      increasingly prevalent drugs are difficult to study in clinical trials due to the
      unethical nature of their consumption. In addition, these medications are
      difficult to study due to the varied usage cycles and patterns, unknown origin
      and source, as well as often high dose ingestion. Physicians and body builders
      need to be aware of the possible serious consequences of their use.

PMID- 30101634
TI  - Urban-rural environmental exposure during childhood and subsequent risk of
      inflammatory bowel disease: a meta-analysis.
AB  - BACKGROUND: The relationship between living conditions in urban and rural areas
      during childhood and subsequent inflammatory bowel disease (IBD) remains
      controversial. AIM: To explore the association between environmental exposures
      early in life and the subsequent risk of IBD. METHODS: Literature searches were
      conducted in the following databases: PubMed, EMBASE, and Conference Proceedings
      Citation Index. Studies were analyzed separately using rate ratios (RRs) or odds
      ratios (ORs) with 95% confidence intervals. RESULTS: The search strategy
      identified 15 studies. Of these, 9 studies explored the association between urban
      exposure during childhood and ulcerative colitis (UC), and 12 and 4 studies
      explored this relationship with Crohn's disease (CD) and IBD, respectively. A
      meta-analysis showed that the pooled ORs estimated for the case-control studies
      of UC, CD, and IBD were 1.16 (0.83, 1.61), 1.45 (1.45, 1.85), and 1.34 (1.11,
      1.62), respectively. The pooled RR estimated for the cohort studies of CD and IBD
      was 1.48 (1.17, 1.87). The stratified analysis and meta-regression showed
      significant relationships between CD and living conditions in case-control
      studies published during 2010-2017 and in non-European countries (P < 0.05).
      CONCLUSIONS: Living conditions during childhood are positively associated with
      the subsequent development of IBD. Urban living environment is more common among
      those with CD than UC.

PMID- 30101636
TI  - Anti-cyclic citrullinated peptide antibodies, 28-joint Disease Activity Score,
      and magnetic resonance imaging bone oedema at baseline predict 11 years'
      functional and radiographic outcome in early rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the clinical and radiographic status, and to identify
      baseline predictors of functional status and erosive progression at 11 years'
      follow-up of early rheumatoid arthritis (RA) patients. METHODS: Patients enrolled
      in the Danish investigator-initiated randomized controlled CIMESTRA trial, which
      investigated a 2 year treat-to-target intervention with methotrexate and intra
      articular glucocorticoids with or without cyclosporine, were followed up. The 28
      joint Disease Activity Score (DAS28), Health Assessment Questionnaire (HAQ)
      score, and total Sharp van der Heijde score (TSS) were assessed at baseline and
      11 years. Baseline magnetic resonance imaging (MRI) of unilateral wrists was
      scored (OMERACT RAMRIS). Multivariable linear regression analyses of baseline
      variables [TSS, HAQ, DAS28, age, anti-cyclic citrullinated peptide (anti-CCP)
      status, gender, MRI erosion score, MRI synovitis score, MRI bone marrow oedema
      score] were performed in 96 patients with HAQ11yrs and ?TSS0-11yrs as dependent
      variables. Since outcomes were similar in the two treatment arms, data were
      pooled. RESULTS: In total, 120 of 160 patients completed 11 years' follow-up.
      They were 63 (55-72) years old, 68% were in DAS28 remission (<= 2.4), HAQ11yrs
      was 0.25 (0-0.75), mean ?TSS0-11yrs was 0.96 +/- 1.52 units/year; 53%, 20%, and
      27% received conventional treatment, biologics, and no treatment, respectively;
      and 34% had not progressed radiographically since baseline. Increased DAS28 (p =
      0.02) and anti-CCP (p = 0.03) predicted HAQ11yrs, whereas anti-CCP (p = 0.03) and
      MRI bone marrow oedema (p = 0.01) predicted ?TSS0-11yrs in multivariable
      analyses. CONCLUSIONS: Early and strict synovitis suppression with methotrexate
      and intra-articular glucocorticoids led to persistently high remission rates and
      limited erosive progression at 11 years. In this well-treated cohort, baseline
      anti-CCP status, DAS28, and MRI bone marrow oedema predicted functional status
      and/or erosive progression.

PMID- 30101638
TI  - The Social Justice Context of Holistic Nursing.

PMID- 30101639
TI  - Nurses' Experiences of Grief Following Patient Death: A Qualitative Approach.

PMID- 30101637
TI  - Sex and Labor Trafficking in Paraguay: Risk Factors, Needs Assessment, and the
      Role of the Health Care System.
AB  - Trafficking of adults and children for both sex and labor is a human rights
      violation occurring with alarming frequency throughout the world, and resulting
      in profound harm to close-knit communities and severe health consequences for
      victims. Certain areas, such as the country of Paraguay, are at a higher risk for
      trafficking due to unique economic, cultural, and geographic factors. Thousands
      of people, especially children, are trafficked within Paraguay's borders, and
      many eventually are transported to neighboring countries and sometimes to Europe
      and elsewhere. Using case study methodology and "city" as the unit of study,
      researchers interviewed 18 key anti-trafficking stakeholders from government and
      nongovernmental organizations in two major metropolitan centers for trafficking
      in Paraguay, Asuncion, and Encarnacion. Through semistructured interviews, this
      qualitative study examines risk factors for trafficking, health outcomes,
      interventions needed within the health care sector, and programs needed to combat
      trafficking. We identified risk factors including poverty, marginalization of
      indigenous people, gender inequality, domestic servitude of children (criadazgo),
      and political hesitance to enact protective legislation. Victims of trafficking
      were reported to suffer from physical injuries, unintended pregnancies, sexually
      transmitted infections, and mental health issues such as depression and
      posttraumatic stress disorder. These predispose victims to difficulties
      reintegrating into their communities and ultimately to retrafficking. A major gap
      was identified in the lack of sufficient lodging and rehabilitation services for
      rescued victims, affordable access to trauma-sensitive health care for victims,
      and scarce mental health services. Many of the findings are applicable across the
      world and may be of use to guide future anti-trafficking efforts in Paraguay and
      beyond.

PMID- 30101640
TI  - Toxicity mechanism-based prodrugs: glutathione-dependent bioactivation as a
      strategy for anticancer prodrug design.
AB  - INTRODUCTION: 6-Mercaptopurine (6-MP) and 6-thioguanine (6-TG), two anticancer
      drugs, have high systemic toxicity due to a lack of target specificity.
      Therefore, increasing target selectivity should improve drug safety. Areas
      covered: The authors examined the hypothesis that new prodrug designs based upon
      mechanisms of kidney-selective toxicity of trichloroethylene would reduce
      systemic toxicity and improve selectivity to kidney and tumor cells. Two
      approaches specifically were investigated. The first approach was based upon
      bioactivation of trichloroethylene-cysteine S-conjugate by renal cysteine S
      conjugate beta-lyases. The prodrugs obtained were kidney-selective but exhibited
      low turnover rates. The second approach was based on the toxic mechanism of
      trichloroethylene-cysteine S-conjugate sulfoxide, a Michael acceptor that
      undergoes rapid addition-elimination reactions with biological thiols. Expert
      opinion: Glutathione-dependent Michael addition-elimination reactions appear to
      be an excellent strategy to design highly efficient anticancer drugs. Targeting
      glutathione could be a promising approach for the development of anticancer
      prodrugs because cancer cells usually upregulate glutathione biosynthesis and/or
      glutathione S-transferases expression.

PMID- 30101641
TI  - Visibility Graph Analysis of Intraspinal Pressure Signal Predicts Functional
      Outcome in Spinal Cord Injured Patients.
AB  - To guide management of patients with acute spinal cord injuries, we developed
      intraspinal pressure monitoring from the injury site. Here, we examine the
      complex fluctuations in the intraspinal pressure signal using network theory. We
      analyzed 7097 h of intraspinal pressure data from 58 patients with severe cord
      injuries. Intraspinal pressure signals were split into hourly windows. Each
      window was mapped into a visibility graph as follows. Vertical bars were drawn at
      0.1 Hz representing signal amplitudes. Each bar produced a node, thus totalling
      360 nodes per graph. Two nodes were linked with an edge if the straight line
      through the nodes did not intersect a bar. We computed several topological
      metrics for each graph including diameter, modularity, eccentricity, and small
      worldness. Patients were followed up for 20 months on average. Our data show that
      the topological structure of intraspinal pressure visibility graphs is highly
      sensitive to pathological events at the injury site, including cord compression
      (high intraspinal pressure), ischemia (low spinal cord perfusion pressure), and
      deranged autoregulation (high spinal pressure reactivity index). These
      pathological changes correlate with long graph diameter, high modularity, high
      eccentricity and reduced small-worldness. In a multivariate logistic regression
      model, age, neurological status on admission, and average node eccentricity were
      independent predictors of neurological improvement. We conclude that analysis of
      intraspinal pressure fluctuations after spinal cord injury as graphs, rather than
      as time series, captures clinically important information. Our novel technique
      may be applied to other signals recorded from injured central nervous system
      (CNS); for example, intracranial pressure, tissue metabolite, and oxygen levels.

PMID- 30101642
TI  - Provoked Narcissistic Aggression: Examining the Role of De-Escalated and
      Escalated Provocations.
AB  - Theories have postulated why provocation is particularly likely to incite
      aggression for narcissists, but key propositions from such theories dealing with
      psychological process or boundary conditions have seldom been tested. Here, we
      investigated narcissists' cognitive, emotional, and motivational experience and
      aggression following escalated and de-escalated provocation. Participants ( N =
      680) completed measures of grandiose narcissism (normal and pathological
      expressions) and vulnerable narcissism. Next, participants simulated provocation
      via imagining everyday scenarios in which a provocateur either de-escalates
      (apologizes and expresses concern) or escalates (makes a spiteful remark) the
      provocation and then rated anger and humiliation, perceived "narcissistic
      injury," goals, and aggression. Expressions of grandiose narcissism, but
      vulnerable narcissism, more strongly related to aggression following escalated
      (vs. de-escalated) provocation. Path modeling revealed that perceived
      narcissistic injury and narcissistic-identity goals explained this relation for
      pathological grandiose narcissists, and revenge goals and narcissistic-identity
      goals explained this relation for normal grandiose narcissists. Conversely,
      vulnerable narcissism related more strongly to anger, perceived narcissistic
      injury, and narcissistic-identity goals following de-escalated (vs. escalated)
      provocation. Path modeling revealed that vulnerable narcissists' enhanced anger
      induced aggression is bounded to de-escalated provocation. We discuss the
      findings in relation to various theories of provoked narcissistic aggression.

PMID- 30101643
TI  - Corrigendum.

PMID- 30101645
TI  - Effect of (-)-epicatechin-3-gallate and (-)-epigallocatechin-3-gallate on the
      binding of tegafur to human serum albumin as determined by spectroscopy,
      isothermal titration calorimetry, and molecular docking.
AB  - Green tea has attracted great interest as a cancer prevention agent. Interactions
      of tea polyphenols with serum albumin may influence the efficacy of drugs. The
      interactions of (-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate
      (ECG), and tegafur (TF) alone or in combination with human serum albumin (HSA) at
      pH 7.4 and different temperatures were investigated by spectroscopic methods,
      isothermal titration calorimetry (ITC), and molecular docking. The binding
      affinities to HSA were ranked in the order of EGCG > ECG > TF, and the
      interactions were spontaneous and exothermic. Ternary system studies showed that
      the presence of one component hindered the binding of another component to HSA.
      The secondary structures of HSA were slightly altered in the presence of the
      ligands. Site marking experiments and molecular docking showed that EGCG and ECG
      mainly bound to subdomain IIA and IotaIotaIotaA while TF bound to subdomain
      IotaIotaA and IotaB. Results indicated that the existence of ECG and EGCG would
      influence the binding of TF to HSA and can increase the free concentration of TF.
      Obtained results would provide beneficial information about possible interference
      upon simultaneous co-administration of the tea components and drugs. Communicated
      by Ramaswamy H. Sarma.

PMID- 30101644
TI  - Apalutamide for the treatment of prostate cancer.
AB  - INTRODUCTION: Five new agents have been shown to prolong survival in patients
      with metastatic castration-resistant prostate cancer, including two targeting
      androgen receptor signaling (abiraterone acetate plus prednisone; enzalutamide).
      Recognition that these tumors remain driven by androgen receptor signaling has
      prompted clinical evaluation of these agents at earlier states in the prostate
      cancer disease continuum, along with the continued development of new agents
      targeting this pathway. Areas covered: This article focuses on apalutamide, a
      next-generation nonsteroidal antiandrogen, with current literature queried in
      PubMed/Medline. A narrative review strategy describes studies from engineering of
      the compound through to a 5-year outlook. Expert commentary: In the phase III
      SPARTAN study, apalutamide significantly improved metastasis-free survival in
      patients with nonmetastatic castration-resistant prostate cancer - the first
      treatment approved by the US Food and Drug Administration for this indication.
      Phase III studies are under way to determine the clinical benefit of apalutamide
      in other disease states. Given the multiplicity of prostate cancer treatment
      options now available, there is a need to maximize individual patient benefit
      through the development and validation of predictive biomarkers of sensitivity to
      drugs that can be used in real time to determine the optimal sequence and
      combinations of treatments for patients in need.

PMID- 30101646
TI  - Early application of an intermittent pneumatic compression device assists
      dilation of radiocephalic fistulas.
AB  - INTRODUCTION: Radiocephalic fistulas are the preferred type of arteriovenous
      fistula due to their advantageous location. However, radiocephalic fistula
      maturation has historically been inferior to brachiocephalic fistulas. Research
      indicates that intermittent compression may aid in forearm vein dilation. Early
      use of a compression device may assist radiocephalic fistula maturation.
      OBJECTIVES: This prospective, randomized, placebo controlled study evaluates
      device safety and the effect of intermittent compression on vein size of
      radiocephalic fistulas and brachiocephalic fistulas. METHODS: This was an
      institutional review board-approved study. After fistula creation, a novel,
      intermittent pneumatic compression device (Fist Assist(r)) was worn 15 cm
      proximal to fistulas 6 h daily for 30 days. Those in the treatment group (n = 43)
      wore Fist Assist(r) (24 with brachiocephalic fistulas and 19 with radiocephalic
      fistulas). Clinical controls (n = 16) wore a sham device. Vein diameter was
      measured at 0 and 30 days by duplex measurement. Percentage increase was recorded
      and tested for significance. RESULTS: After 30 days, the mean percentage increase
      in vein diameter in the radiocephalic fistula treatment group was significantly
      larger than brachiocephalic fistulas in the treatment group at all proximal
      locations from the anastomosis. Increases in percentage vein dilation for those
      in the radiocephalic fistula treatment group were significantly larger than those
      in the control group. All fistulas treated with Fist Assist(r) are still
      functional with no reported complications. CONCLUSION: Early application of the
      Fist Assist(r) device may be more effective at helping radiocephalic fistula
      mature as compared to brachiocephalic fistulas. Successful radiocephalic fistula
      maturation may decrease vascular access costs, reduce complications, and preserve
      upper arm veins for future use in vascular access.

PMID- 30101647
TI  - Human Co- and Triple-Culture Model of the Alveolar-Capillary Barrier on a
      Basement Membrane Mimic.
AB  - The development of an in vitro model resembling the alveolar-capillary barrier
      might be a highly beneficial tool to study lung physiology as well as the immune
      response of the lung to infection or after exposure to nanoparticles. This study
      is based on an in vitro alveolar barrier developed on a basement membrane mimic,
      composed of ultrathin nanofiber meshes generated via electrospinning using
      bioresorbable poly(E-caprolactone). As cellular components, NCI H441, resembling
      the alveolar epithelial cells, and ISO-HAS-1, an endothelial cell line, were used
      to perform bipolar coculture experiments for a total cultivation period of 14
      days. In addition to immunohistochemical and immunofluorescent studies,
      transepithelial electrical resistance (TER) and transport capabilities of the in
      vitro model system were investigated. Alveolar barrier function could be clearly
      determined for the postulated bipolar coculture system on the basement membrane
      mimic, since TER increased during the course of bipolar cultivation. Furthermore,
      to gain first insights into possible lung inflammatory reactions in vitro, this
      coculture model was further expanded by a human leukemia monocyte cell line (THP
      1). This triple-culture system was able to maintain adequately the barrier
      properties of the bipolar coculture, thus making this in vitro model consisting
      of epithelial, endothelial, and immune cells on a basement membrane mimic a
      promising basis for further studies in tissue engineering.

PMID- 30101648
TI  - A Brief Computer-Based Sexual Assault Risk Reduction Program: A Feasibility,
      Acceptability, and Preliminary Efficacy Pilot Study.
AB  - Sexual victimization among college women is a common problem, necessitating the
      development of risk reduction programs that are both effective and acceptable to
      this population. Computer-based programs may be a cost- and time-effective
      option. This pilot study sought to examine the feasibility, acceptability, and
      preliminary efficacy of a computer-based risk reduction program. A total of 136
      collegiate women were randomly assigned to receive either a computer-based risk
      reduction program or an educational program about campus resources (active
      control condition). Measures included predicted use of resistance techniques,
      risk detection, and acceptability of the program. No participants dropped out of
      the study, and acceptability ratings were generally high. Women reported learning
      new material from the program, preferring the computer-based program to large
      group programs, and believing that other undergraduate women would benefit from
      the program. Furthermore, women reported they did not experience significant
      emotional disturbance due to the material. In addition, postintervention, the
      risk reduction program group had significantly better risk detection compared
      with the control group. The control group evidenced a reduction in predicted use
      of assertive resistance between pre- and postintervention assessments, while the
      risk reduction program group did not. Given preliminary support for the
      feasibility, acceptability, and preliminary efficacy of a brief, computerized
      risk reduction program, further research on computerized, online risk reduction
      programs, such as the one in this study, appears warranted.

PMID- 30101650
TI  - Parametric design of patient-specific fixation plates for distal femur fractures.
AB  - To facilitate the creation, modification, and optimization of patient-specific
      plates for distal femur fractures, a novel approach was proposed for the rapid
      and convenient design of patient-specific plates for patients' fractured femurs
      using feature parameterization. First, several femur parameter values were
      obtained for a specific patient and used to construct a restored surface model of
      the fractured femur. Next, combined with the particular femur anatomy and the
      fracture, a parameterized plate with a suitable shape was created automatically
      based on the parameter maps between the femur and plate. Finally, using finite
      element analysis, the Von Mises stresses of the plate under human gait loads were
      calculated to evaluate the biomechanical performance of the plate, and the plate
      was optimized for specific patients by recursively adjusting the parameter
      values. Case results indicate that patient-specific plate models can be created
      rapidly based on the fractured femur modes of patients and can be optimized
      efficiently with high-level semantic parameters. Therefore, the proposed approach
      may be used as a basic tool for the design and modification of patient-specific
      plates for use in orthopedic operations.

PMID- 30101649
TI  - Direct and indirect pro-inflammatory cytokine response resulting from TC-83
      infection of glial cells.
AB  - Venezuelan equine encephalitis virus (VEEV) is a neurotropic arbovirus that is
      highly infectious as an aerosol and can result in an encephalitic phenotype in
      infected individuals. VEEV infections are known to be associated with robust
      inflammation that eventually contributes to neurodegenerative phenotypes. In this
      study, we utilize the TC-83 strain of VEEV, which is known to induce the
      expression of IL-6, IL-8, and other pro-inflammatory cytokines. We had previously
      demonstrated that TC-83 infection resulted in changes in mitochondrial function,
      eventually resulting in mitophagy. In this manuscript, we provide data that links
      upstream mitochondrial dysfunction with downstream pro-inflammatory cytokine
      production in the context of microglia and astrocytoma cells. We also provide
      data on the role of bystander cells, which significantly contribute to the
      overall inflammatory load. Use of a mitochondrial-targeted antioxidant,
      mitoquinone mesylate, greatly reduced the inflammatory cytokine load and
      ameliorated bystander cell inflammatory responses more significantly than a broad
      spectrum anti-inflammatory compound (BAY 11-7082). Our data suggest that the
      inflammatory mediators, especially IL-1beta, may prime naive cells to infection
      and lead to increased infection rates in microglial and astrocytoma cells.
      Cumulatively, our data suggest that the interplay between mitochondrial
      dysfunction and inflammatory events elicited in a neuronal microenvironment
      during a TC-83 infection may contribute to the spread of infection.

PMID- 30101654
TI  - "New Kid on the Block": Family Nursing Initiatives in the Netherlands.

PMID- 30101651
TI  - Erratum.
AB  - Moriarty, H., Winter, L., Short, T. H., & True, G. (2018). Exploration of factors
      related to depressive symptomatology in family members of military veterans with
      traumatic brain injury. Journal of Family Nursing, 24, 184-216. doi:
      10.1177/1074840718773470 .

PMID- 30101655
TI  - Development and Implementation of a Family-Focused Undergraduate Nursing
      Curriculum: Minnesota State University, Mankato.
AB  - Nurse educators have the responsibility to create learning experiences centered
      on the scientific and praxis foci of the nursing discipline to advance nursing
      practice with families. Although the nursing profession has ample knowledge about
      the importance of family nursing and the value of family-focused actions, there
      is a lack of curricular and teaching models that address nursing practice with
      families in numerous courses and learning experiences. This article describes the
      development of a family-focused undergraduate curriculum and teaching-learning
      practices at Minnesota State University, Mankato in the United States. A vision
      and mission centered on the nursing of families, a family care teaching model, a
      framework of family constructs, and taxonomy of significant learning strategies
      guided faculty in creating learner-centered experiences. Course objectives,
      competencies, and teaching-learning practices in this curriculum are described.
      This manuscript may guide the development of innovative teaching-learning
      practices that integrate family nursing constructs and family nursing actions
      from a variety of family nursing models and theories. Initial evaluation suggests
      that this curriculum can increase students' knowledge of family and instill a
      passion for family care in undergraduate programs.

PMID- 30101656
TI  - Effects of secondary structures of DNA templates on the quantification of qPCR.
AB  - In the current design of qPCR systems, the sequences of primers are the primary
      concerns. The secondary structures of DNA templates have not been much
      considered, although they should be also critically important. In this paper,
      various hairpins with different stem lengths and loop sizes are placed near
      primer-binding sites, and their effects on the amplification efficiency of qPCR
      are systematically investigated. When a hairpin is formed either in the inside of
      the amplicon or in its outside, the amplification is notably suppressed. The
      magnitudes of suppression increase with the increase of stem length and the
      decrease of loop size, and are especially significant for the hairpins formed
      inside the amplicon. With very long stems (e.g., 20-bp), the effect is still more
      drastic, and no targeted amplification products are formed. On the basis of
      melting temperature (Tm) measurements, these suppression effects of hairpins have
      been mostly ascribed to competitive inhibition of primer binding to the template.
      It has been concluded that, in order to design precise and reliable qPCR systems,
      at least 60-bp sequences around primer-binding sites, both inside and outside the
      amplicons, must be analyzed to confirm that stable secondary structures are not
      formed in the vicinity of primer-binding sites.

PMID- 30101657
TI  - What is holding up the Unified Patent Court?
AB  - A form of unified patent protection has been available in Europe since the 1970s,
      but enforcement remains purely a national matter. After many years' negotiation,
      an agreement was signed in February 2013 to create a pan-European court (the
      UPC), potentially affecting global litigation strategies. A constitutional
      complaint brought in Germany in 2017 has delayed the project and potentially
      presents an existential challenge, but more likely the issue is how much further
      delay it will cause. It remains entirely possible the UPC will start in Q1 2019
      (before Brexit). In addition, for patentees such as pharmaceutical companies
      requiring broad geographic protection, another part of the new system, the
      unitary patent, would also mean a dramatic reduction in patent maintenance costs.

PMID- 30101659
TI  - Bootstrapping and Empirical Bayes Methods Improve Rhythm Detection in Sparsely
      Sampled Data.
AB  - There is much interest in using genome-wide expression time series to identify
      circadian genes. However, the cost and effort of such measurements often limit
      data collection. Consequently, it is difficult to assess the experimental
      uncertainty in the measurements and, in turn, to detect periodic patterns with
      statistical confidence. We show that parametric bootstrapping and empirical Bayes
      methods for variance shrinkage can improve rhythm detection in genome-wide
      expression time series. We demonstrate these approaches by building on the
      empirical JTK_CYCLE method (eJTK) to formulate a method that we term BooteJTK.
      Our procedure rapidly and accurately detects cycling time series by combining
      information about measurement uncertainty with information about the rank order
      of the time series values. We exploit a publicly available genome-wide data set
      with high time resolution to show that BooteJTK provides more consistent rhythm
      detection than existing methods at typical sampling frequencies. Then, we apply
      BooteJTK to genome-wide expression time series from multiple tissues and show
      that it reveals biologically sensible tissue relationships that eJTK misses.
      BooteJTK is implemented in Python and is freely available on GitHub at
      https://github.com/alanlhutchison/BooteJTK .

PMID- 30101660
TI  - Rituals of global health: Negotiating the World Health Assembly.
AB  - The World Health Assembly is the WHO's supreme decision-making body and consists
      of representatives from the 194 WHO Member States who take formal decisions on
      the WHO's policies, workplan and budget. The event is also attended by
      representatives of non-governmental organisations, the private sector, the press
      and even members of the public. Based on participant observation at six World
      Health Assemblies, in-depth interviews with 53 delegates to the WHA, and an
      analysis of WHA Official Records, this article examines the ritualistic aspects
      of WHA negotiations. We argue that analysing the WHA as a ritual provides an
      insight into power and legitimacy within global health. Not only are certain
      understandings of health issues and courses of actions decided by the Assembly,
      but also the very boundaries of global health community are set. The rules of the
      ritual place limits on different categories of actors, while both formal and
      informal rules of behaviour further serve to include or exclude actors from the
      rituals. Success in negotiation is measured by through the inclusion of certain
      ideas, norms and values in the wording of resolutions and is achieved through the
      repetition of language in speeches and by adhering to the rules of behaviour.

PMID- 30101661
TI  - Engaging a Community Leader to Enhance Preparation for In-Depth Interviews With
      Community Members.
AB  - In-depth interviews allow for rich exploration of stakeholders' experiences.
      Preparation for in-depth interviews generally consists of literature reviews and
      researchers' review of their own culture and understanding of a topic. We
      supplemented these strategies with serial "ethnographic interviews" with a single
      community leader to enhance our preparation for community-based in-depth
      interviews with Latina, immigrant, Spanish-speaking mothers and to facilitate
      stakeholder engagement in a research project. After an extensive literature
      review, we conducted a series of four 1-hour interviews with a key informant in
      preparation for individual in-depth interviews with 12 parents. The ethnographic
      interviews with the community leader provided insight into environmental context,
      cultural categories, and stakeholder priorities, which helped shape the research
      question, in-depth interview guide, sampling strategy, and interpretive analytic
      process. We found that ethnographic interviews can provide critical insights for
      preparing in-depth interview guides and can enhance the information gained while
      facilitating meaningful stakeholder engagement.

PMID- 30101662
TI  - When the Hospital Is No Longer an Option: A Multiple Case Study of Defining
      Moments for Women Choosing Home Birth in High-Risk Pregnancies in The
      Netherlands.
AB  - Some women in a high-risk pregnancy go against medical advice and choose to birth
      at home with a "holistic" midwife. In this exploratory multiple case study,
      grounded theory and triangulation were employed to examine 10 cases. The women,
      their partners, and (regular and holistic) health care professionals were
      interviewed in an attempt to determine whether there was a pattern to their
      experiences. Two propositions emerged. The dominant one was a trajectory of
      trauma, self-education, concern about paternalism, and conflict leading to a
      negative choice for holistic care. The rival proposition was a path of trust and
      positive choice for holistic care without conflict. We discuss these two
      propositions and make suggestions for professionals for building a trusting
      relationship using continuity of care, true shared decision making, and an
      alternative risk discourse to achieve the goal of making women perceive the
      hospital as safe again.

PMID- 30101663
TI  - Interacting With Providers: An Intersectional Exploration of the Experiences of
      Carers of Aboriginal Children With a Disability.
AB  - Intersectionality has potential to create new ways to describe disparities and
      craft meaningful solutions. This study aimed to explore Aboriginal carers'
      experiences of interactions with health, social, and education providers in
      accessing services and support for their child. Carers of Aboriginal children
      with a disability were recruited from an Australian metropolitan Aboriginal
      community-controlled health service. In-depth, semistructured interviews were
      conducted with 19 female carers. Intersectionality was applied as an analytical
      framework due to the inherent power differentials for Aboriginal Australians and
      carers for people with a disability. Marginalization and a lack of empowerment
      were evident in the experiences of interactions with providers due to cultural
      stereotypes and racism, lack of cultural awareness and sensitivity, and poverty
      and homelessness. Community-led models of care can help overcome the
      intersectional effects of these identities and forms of oppression in carers'
      interactions with providers and enhance access to care.

PMID- 30101664
TI  - "I really want people to use our work to be safe"...Using participatory research
      to develop a safety intervention for adults with intellectual disability.
AB  - People with intellectual disability experience disproportionately high rates of
      interpersonal violence (IPV) due, in part, to disability-related risks that often
      can be minimized through targeted intervention. In this article, we describe
      using an academic and community participatory research approach to develop and
      test the feasibility of an accessible IPV prevention program for people with
      intellectual disability. The Safety Class, which is an interactive, structured,
      eight-session, weekly face-to-face group program, was found feasible for
      implementation in an efficacy study. Working in partnership with the intellectual
      disability community through all phases of the project helps ensure the
      relevance, inclusion, and accessibility of The Safety Class.

PMID- 30101665
TI  - First Report of Sweet Potato Symptomless Virus 1 Infecting Ipomoea batatas in
      Brazil.

PMID- 30101666
TI  - Occurrence of Outbreak of Leaf Spot Caused by Corynespora cassiicola in
      Strawberry in China.

PMID- 30101667
TI  - Mini-plate fixation via sinus tarsi approach is superior to cannulated screw in
      intra-articular calcaneal fractures: A prospective randomized study.
AB  - OBJECTIVE: Intra-articular displaced calcaneal fractures are common fractures and
      are often treated with surgical interventions. Sinus tarsi approach provides
      secure access to lateral wall and joint facets. The aim of the study is to
      compare cannulated screw (CS) fixation and mini-plate (MP) fixation via sinus
      tarsi approach with Sanders types 2 and 3 fracture of calcaneus. METHODS: Sixty
      patients with Sanders types 2 and 3 calcaneal fracture underwent surgical
      intervention were randomly allocated into two groups as group MP fixation and
      group CS fixation regarding osteosynthesis method for 5-year period. Open
      reduction via sinus tarsi approach was performed in both groups. Demographic
      variables, time to surgery (TS), operation duration (OD), length of hospital stay
      (LOS), surgical complications, and reoperations were recorded. Pre- and
      postoperative Gissane and Bohler angles; calcaneal length, height, and width;
      ankle anterior-posterior (AP) and lateral X-rays; and computed tomography were
      also recorded for radiological evaluation and fracture characteristics. Maryland
      Foot Score (MFS) was used to evaluate functional outcomes. RESULTS: Preoperative
      age, type of fracture, calcaneal length, height, and Gissane and Bohler angles,
      TS, LOS, and OD were not different between the groups. The postoperative
      calcaneal widening was significantly better restored in group MP compared with
      that of group CS. The incidence of reoperation and algoneurodystrophy was
      statistically higher in group CS than group MP. MFS in group MP was also higher
      than group CS at final visit. CONCLUSION: MP fixation via sinus tarsi approach is
      superior to CS fixation in Sanders types 2 and 3 calcaneal fractures.

PMID- 30101669
TI  - Corrigendum.
AB  - Benjamin, A. J., Jr., Kepes, S., & Bushman, B. J. (2017). Effects of weapons on
      aggressive thoughts, angry feelings, hostile appraisals, and aggressive behavior:
      A meta-analytic review of the weapons effect literature. Personality and Social
      Psychology Review. (Original DOI: 10.1177/1088868317725419 ).

PMID- 30101668
TI  - A Drug Eluting Scaffold for the Treatment of Arthrofibrosis.
AB  - INTRODUCTION: The inflammatory cascade and production of prostaglandins may play
      a role in the pathogenesis of arthrofibrosis, a debilitating condition after
      joint replacement and other orthopedic procedures. Cyclooxygenase 2 (COX-2)
      inhibitors may mitigate the inflammatory response and formation of
      arthrofibrosis, but oral delivery is associated with risk of systemic side
      effects in many patients. The nonsteroidal anti-inflammatory drug, celecoxib, may
      have therapeutic benefits for arthrofibrosis, but current methods for its local
      delivery (e.g., biologically derived microspheres) are not translatable to
      immediate clinical use. Therefore, we investigated the use of a drug scaffold for
      sustainable intra-articular delivery of therapeutic doses of celecoxib. MATERIALS
      AND METHODS: Celecoxib was eluted from clinically approved biodegradable collagen
      membranes over 7 days as measured by UV spectroscopy and high-performance liquid
      chromatography/mass spectroscopy. Eluted concentrations of celecoxib were
      examined for toxicity (live/dead staining) and profibrotic gene expression (real
      time-quantitative polymerase chain reaction) in rabbit knee capsular fibroblasts
      in vitro. RESULTS: Sustained concentrations of celecoxib eluted from the membrane
      over 7 days from both a wet and dry scaffold, with a burst release (30-45%) of
      celecoxib in the first 2 h. Rabbit cells treated with eluted concentrations
      experienced a toxic response to the burst release doses, and inhibitory effects
      on profibrotic genes were seen in response to the sustained doses eluted from the
      scaffold. CONCLUSIONS: This study characterized the novel use of collagen
      scaffolds for intra-articular drug delivery to treat arthrofibrosis. Scaffolds
      exhibit celecoxib release through an initial burst release followed by sustained
      release of antifibrotic doses over 7 days. Thus, collagen scaffolds are promising
      for clinician-directed treatment of arthrofibrosis.

PMID- 30101670
TI  - Three-Dimensional Spheroid Primary Human Hepatocytes in Monoculture and Coculture
      with Nonparenchymal Cells.
AB  - Recent advances in the development of various culture platforms are promising for
      achieving more physiologically relevant in vitro hepatic models using primary
      human hepatocytes (PHHs). Previous studies have shown the value of PHHs three
      dimensional (3D) spheroid models, cultured in low cell number (1330-2000 cells/3D
      spheroid), to study long-term liver function as well as pharmacological drug
      effects and toxicity. In this study, we report that only plateable PHHs aggregate
      and form compact 3D spheroids with a success rate of 79%, and 96%
      reproducibility. Out of 3D spheroid forming PHH lots, 65% were considered stable
      (<50% ATP decrease) over the subsequent 14 days of culture, with reproducibility
      of a given PHH lot being 82%. We also report successful coculturing of PHHs with
      human liver nonparenchymal cells (NPCs). Crude P1c-NPC fractions were obtained by
      low centrifugation of the PHH supernatant fraction followed by a few days of
      culture before harvesting and cryopreservation. At aggregation of PHHs/P1c-NPCs
      (2:1 ratio 3D spheroids), liver sinusoidal endothelial cells, Kupffer cells, and
      hepatic stellate cells were successfully integrated and remained present
      throughout the subsequent 14-day culture period as revealed by mRNA expression
      markers and immunostaining. Increased mRNA expression of albumin (ALB),
      apolipoprotein B (APOB), cytochrome P450 3A4 (CYP3A4), and increased albumin
      secretion compared to PHH 3D spheroid monocultures highlighted that in a 3D
      spheroid coculture, configuration with NPCs, PHH functionality is increased. We
      thus achieved the development of a more integrated coculture model system
      requiring low cell numbers, of particular interest due to the scarcity of human
      liver NPCs.

PMID- 30101671
TI  - Trachea Engineering Using a Centrifugation Method and Mouse-Induced Pluripotent
      Stem Cells.
AB  - The outcomes of tracheal transplantation for the treatment of airway stenosis are
      unsatisfactory. We investigated the feasibility of regeneration of the trachea
      using a rat decellularized tracheal scaffold and mouse-induced pluripotent stem
      (iPS) cells for in vivo transplantation. The rat trachea was first decellularized
      using a detergent/enzymatic treatment method. We successfully established a
      centrifugation method that can transplant cells onto the luminal surface of the
      decellularized rat tracheal scaffold circumferentially. Two types of mouse iPS
      cells were differentiated into definitive endoderm cells and transplanted onto
      the luminal surface of the decellularized tracheal matrix scaffold using this
      centrifugation method. For in vivo study, normal rat tracheas, no-cell rat
      tracheal scaffolds, or rat tracheal scaffolds recellularized with rat tracheal
      epithelial cells (EGV-4T) were orthotopically transplanted on F344 rats, and rat
      tracheal scaffolds recellularized with mouse iPS cells were transplanted on
      F344/NJc1-rnu/rnu rats. Rats transplanted with no-cell scaffolds or scaffolds
      recellularized with EGV-4T survived for 1 month, although airway stenosis was
      observed. One of the F344/NJc1-rnu/rnu rats transplanted with rat trachea
      regenerated using mouse iPS cells survived over 5 weeks. Histological analysis
      indicated the cause of death was airway stenosis due to colonic cellular
      proliferation of undifferentiated iPS cells. Re-epithelialization with numerous
      ciliated epithelial cells was observed in one of the rats transplanted with
      trachea bioengineered using iPS cells. In this study, we present a simple and
      efficient tracheal tissue engineering model using a centrifugation method in a
      small-animal model. Tissue-engineered trachea using decellularized tracheal
      scaffolds and iPS cells is potentially applicable for tracheal transplantation.

PMID- 30101672
TI  - Society of Interventional Radiology Reporting Standards for Thoracic Central Vein
      Obstruction: Endorsed by the American Society of Diagnostic and Interventional
      Nephrology (ASDIN), British Society of Interventional Radiology (BSIR), Canadian
      Interventional Radiology Association (CIRA), Heart Rhythm Society (HRS), Indian
      Society of Vascular and Interventional Radiology (ISVIR), Vascular Access Society
      of the Americas (VASA), and Vascular Access Society of Britain and Ireland
      (VASBI).

PMID- 30101673
TI  - Immediate effect of infrapatellar strap on pain and jump height in patellar
      tendinopathy among young athletes.
AB  - BACKGROUND: Infrapatellar strapping is a treatment technique used in various knee
      pathologies; however, its effect on pain and functional performance among young
      athletes has not been studied. OBJECTIVES: To evaluate the effect of
      infrapatellar strap on pain and jumping performance among young athletes
      diagnosed with patellar tendinopathy. STUDY DESIGN: Pre-/post-test (within
      subject research design). METHODS: A total of 16 young male basketball and
      volleyball athletes (age range, 12-18 years) diagnosed with patellar tendinopathy
      were included in the study. Infrapatellar strap was applied beneath the patella,
      over the patellar tendon. The athletes performed four jumping tests: squat jump,
      drop jump, single-leg jump, and jumps 30 s test, with and without the strap. Pain
      severity in the symptomatic knee during jumping was assessed using a visual
      analog scale and jumping performance parameters were assessed using an Optojump
      Next optical measurement system. RESULTS: Pain severity reported by the
      participants decreased in drop test, single-leg jump test, and jumps 30 s test
      while using the infrapatellar strap compared with no strap condition ( p < 0.05).
      No significant difference in jumping performance was found between jumping with
      and without the strap. CONCLUSION: The infrapatellar strap was effective in
      reducing local pain among young male athletes without altered jumping
      performance. Clinical relevance The infrapatellar strap can be recommended to use
      during physical activity as part of the physical therapy treatments for patellar
      tendinopathy. Given the low cost, ease to use, and being a non-invasive method
      without adverse effects, it is an appropriate intervention for young athletes.

PMID- 30101675
TI  - Area-level relative deprivation and alcohol use in Denmark: Is there a
      relationship?
AB  - AIMS: Greater area-level relative deprivation has been related to poorer health
      behaviours, but studies specifically on alcohol use and abuse have been
      equivocal. The main purpose of the present study was to investigate how area
      level relative deprivation in Denmark relates to alcohol use and misuse in the
      country. METHODS: As individual-level data, we used the national alcohol and drug
      survey of 2011 ( n= 5133). Data were procured from Statistics Denmark to
      construct an index of relative deprivation at the parish level ( n=2119). The
      deprivation index has two components, which were divided into quintiles.
      Multilevel linear and logistic regressions analysed the influence of area
      deprivation on mean alcohol use and hazardous drinking, as measured by the
      Alcohol Use Disorder Identification Test. RESULTS: Men who lived in parishes
      designated as 'very deprived' on the socioeconomic component were more likely to
      consume less alcohol; women who lived in parishes designated as 'deprived' on the
      housing component were less likely to drink hazardously. But at the individual
      level, education was positively related to mean alcohol consumption, and higher
      individual income was positively related to mean consumption for women. Higher
      educated men were more likely to drink hazardously. CONCLUSIONS: Area-level
      measures of relative deprivation were not strongly related to alcohol use, yet in
      the same models individual-level socioeconomic variables had a more noticeable
      influence. This suggests that in a stronger welfare state, the impact of area
      level relative deprivation may not be as great. Further work is needed to develop
      more sensitive measures of relative deprivation.

PMID- 30101676
TI  - The osteoinductive effect of controlled BMP-2 release is location-dependent.
AB  - The main challenge in BMP-2 based application lies in finding strategies that
      prolong its effective period, as it has a short biological half-life. Several BMP
      2 release profiles have shown to enhance bone formation at various application
      sites. However, it remains to be determined which BMP-2 release profile best
      augments bone formation and whether this effect is location-dependent. Therefore,
      the aim of this study was to investigate the effect of BMP-2 release from
      oligo[(polyethylene glycol) fumarate] bis(2-(methacryloyloxy)ethyl) phosphate
      (OPF-BP) composites on the osteoinductive efficacy at ectopic versus orthotopic
      application. By varying the BMP-2 loading method, three different OPF-BP
      composites were created with varied release profiles. The composites were
      compared to unloaded OPF-BP as negative control, and to the clinically used
      Infuse(r) absorbable collagen sponge (ACS) as positive control. Bone formation
      was assessed by micro-computed tomography after 9 weeks of subcutaneous
      implantation and 3, 6, and 9 weeks of orthotopic implantation in rats (n=48).
      Whereas a BMP-2 burst release of >49% generated significantly more bone compared
      to sustained release (burst release <30%) at the subcutaneous implantation site,
      differential release did not affect bone formation at the orthotopic site.
      Furthermore, all BMP-2 containing OPF-BP composites showed significantly more
      bone formation compared to ACS in the orthotopic implantation site. In
      conclusion, this study clearly shows that the osteoinductive effect of different
      BMP-2 release profiles is location dependent. Additionally, more bone formation
      in OPF-BP compared to ACS at both application sites emphasizes the role of
      biomaterials as a scaffold to achieve proper bone tissue formation.

PMID- 30101677
TI  - Evaluation of the Effect of Tissue Compression on the Results of Shear Wave
      Elastography Measurements.
AB  - Shear wave imaging is considered to be more precise and less operator dependent
      when compared with strain imaging. It enables quantitative and reproducible data
      (Young's modulus of the imaged tissue). However, results of shear wave imaging
      can be affected by a variety of different factors. The aim of this study is to
      evaluate the effect of the pressure applied by the ultrasound probe during
      examination on the measured values of Young's modulus. The effect of the tissue
      compression on the results of the real-time shear wave elastography was evaluated
      via the gelatine phantom measurements, via the ex vivo experiments with pig
      liver, and via the in vivo measurements of the thyroid gland stiffness on healthy
      volunteers. The results of our measurements confirmed that the measured value of
      Young's modulus increases with the increasing pressure applied on the imaged
      object. The highest increase was observed during the ex vivo experiments (400%),
      and the lowest increase was detected in the case of the phantom measurements
      (8%). A two- to threefold increase in Young's modulus was observed between the
      minimum and maximum pressure in the case of the in vivo elastography measurements
      of thyroid gland. The Veronda-Westman theoretical model was used for the
      description of the tissue nonlinearity. We conclude that tissue compression by
      the force exerted on the probe can significantly affect the results of the real
      time shear wave elastography measurements. Minimum pressure should be used when
      measuring the absolute value of Young's modulus of superficial organs.

PMID- 30101678
TI  - Cultivating Compassion: The Practice Experience of a Medical Assistance in Dying
      Coordinator in Canada.
AB  - Accessing medical assistance in dying (MAiD) became legal in Canada in June,
      2016. This marks a unique time in our history, as eligible persons can now opt
      for an assisted death and health care professionals can be involved without
      criminal repercussion. I used an autoethnographic approach to explore and
      describe my experience of implementing and coordinating a new MAiD program in a
      local health authority. Part I is a self-reflexive narrative based on journal
      entries about my immersion in this practice role over a 6 month period. In Part
      II, I share five emergent storylines: coming to the role (the calling),
      embodiment (becoming the face of), immersion in clinical practice, interactions
      with those seeking MAiD, and self survival (sense making). The created story and
      storylines shine a light on new ethical practice realities, enhance understanding
      about MAiD as it continues to unfold, and hopefully inspire human centered,
      compassionate care.

PMID- 30101679
TI  - Efficacy and tolerability of rituximab and reduced-dose cyclophosphamide,
      doxorubicin, vincristine, and prednisolone therapy for elderly patient with
      diffuse large B-cell lymphoma.
AB  - OBJECTIVES: Chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine,
      and prednisolone combined with rituximab (R-CHOP) is currently the first-line
      therapy for diffuse large B-cell lymphoma (DLBCL). However, management of elderly
      patients is challenging and often requires dose reductions or prolonged treatment
      intervals. We investigated the proper dose of R-CHOP for them. METHODS: At our
      institute, for DLBCL patients aged 65-79 and >=80 years, we had reduced CHOP dose
      to 5/6 and 7/12, respectively, and retrospectively evaluated the reduced-dose R
      CHOP. RESULTS: Although the median age in the standard, 5/6, and 7/12-dose groups
      was 57, 73, and 84 years, respectively (p < 0.001), the 3-year event-free
      survival (EFS) rate did not differ between the standard and 5/6-dose groups (60.2
      and 56.7%); however, 7/12-dose group had significantly inferior survival (25.9%).
      When patients aged 60-80 were evaluated, no difference in EFS was observed
      between the standard and 5/6-dose groups using the same international prognostic
      index. The neutrophil nadir and the frequency of infection were comparable among
      the three dose groups. DISCUSSION AND CONCLUSIONS: Reduced-dose R-CHOP
      chemotherapy is a promising treatment for elderly patients with DLBCL in terms of
      efficacy and toxicity.

PMID- 30101680
TI  - Nighttime bracing with the Providence thoracolumbosacral orthosis for treatment
      of adolescent idiopathic scoliosis: A retrospective consecutive clinical series.
AB  - BACKGROUND: Orthotic treatment for adolescent idiopathic scoliosis is a mainstay
      in nonoperative treatment to prevent progressive spinal deformity. OBJECTIVE: To
      determine the effectiveness of the Providence orthosis in the treatment of
      adolescent idiopathic scoliosis. STUDY DESIGN: Retrospective review. METHODS:
      Patients treated with a Providence orthosis for adolescent idiopathic scoliosis
      were reviewed. Inclusion criteria included the following: age of 10-18 years;
      curve magnitude of 25 degrees -40 degrees ; Risser stage of 0-2; and, if female,
      <1 year post menarche at the time of brace initiation. Failure was defined as
      curve magnitudes progressing >5 degrees  or to >45 degrees  or surgery.
      Radiographs and clinical information were recorded and compared between treatment
      success and failure cohorts. RESULTS: 56 patients (51 female and 5 male; average
      of 12.26 years) were identified with average of 2.21-year follow-up and a 57.1%
      success rate for preventing curve progression. Factors associated with successful
      treatment included curve apex T10 and caudal and Risser sign ? 1. Multivariate
      analysis identified Risser ? 1 and curve apex T10 and caudal as independent
      predictors of successful treatment. CONCLUSION: The Providence nighttime orthosis
      can be an effective treatment for adolescent idiopathic scoliosis. Curve Apex at
      T10 or caudal was an independent predictors of treatment success. Clinical
      relevance This study identifies variables associated with treatment success using
      the Providence nighttime orthosis in a consecutive series of adolescent
      idiopathic scoliosis patients. This information provides the foundation for
      identifying ideal patients for nighttime bracing to guide clinical treatment.

PMID- 30101682
TI  - Gaitography on lower-limb amputees: Repeatability and between-methods agreement.
AB  - BACKGROUND: Gaitography is gait parametrization from center-of-pressure
      trajectories of walking on an instrumented treadmill. Gaitograms may be useful
      for prosthetic gait analyses, as they can be rapidly and unobtrusively collected
      over multiple gait cycles without constraining foot placement. However, its
      reliability must still be established for prosthetic gait. OBJECTIVES: To
      evaluate (a) within-method test-retest repeatability and (b) between-methods
      agreement for temporal gait events (foot contact, foot off) and gait
      characteristics (e.g. step times, single-support duration). STUDY DESIGN: Cohort
      study with repeated measurements. METHODS: Ten male proficient prosthetic walkers
      with a unilateral trans-femoral or trans-tibial amputation were equipped with a
      pressure-insole system and were invited to walk on separate days on an
      instrumented treadmill. RESULTS: We found better between-methods reproducibility
      than within-method repeatability in temporal gait characteristics. Step times,
      stride times, and foot-contact events matched well between the two methods. In
      contrast, insole-based foot-off events were detected one-to-two samples earlier.
      Likewise, a similar bias was observed for temporal gait characteristics that
      incorporated foot-off events. CONCLUSION: Notwithstanding small systematic
      biases, the good between-methods agreement indicates that temporal gait
      characteristics may be determined interchangeably with gaitograms and insoles in
      persons with a prosthesis. However, the relatively poorer test-retest
      repeatability hinders longitudinal assessments with either method. CLINICAL
      RELEVANCE: Clinical practice could potentially benefit from gaitography as an
      efficient, unobtrusive, easy to use, automatized, and patient-friendly means to
      objectively parametrize prosthetic gait, with immediate availability of test
      results allowing for prompt clinical decision-making. Temporal gait parameters
      demonstrate good between-methods agreement, but poorer within-method
      repeatability hinders detecting prosthetic gait changes.

PMID- 30101681
TI  - Comparison of the effect of foot orthoses on Star Excursion Balance Test
      performance in patients with chronic ankle instability.
AB  - BACKGROUND: Chronic ankle instability as a prevalent consequence of ankle sprain
      causes various impairments such as balance and postural control deficits. Foot
      orthoses are one of the common interventions for rehabilitation of patients with
      chronic ankle instability. OBJECTIVES: To investigate the effect of custom-molded
      foot orthoses with textured surfaces on dynamic balance of chronic ankle
      instability patients and to compare their effects with other types of foot
      orthoses. STUDY DESIGN: This is a repeated measure design. METHODS: A total of 30
      participants were recruited based on the guideline introduced by the
      International Ankle Consortium. The effect of prefabricated, custom-molded, and
      custom-molded with textured surface foot orthoses was evaluated on dynamic
      balance by the Star Excursion Balance Test. Normalized reach distances in
      anteromedial, medial, and posteromedial directions of the test were computed to
      be used for statistical analysis. RESULTS: The foot orthoses increased reach
      distances compared to the no-orthosis conditions in all three directions. The
      custom-molded with textured surface foot orthosis has significant differences
      compared with prefabricated foot orthosis ( p = 0.001) in all measured directions
      and with custom-molded foot orthosis ( p < 0.01) in medial and posteromedial
      directions. CONCLUSION: Foot orthoses improve reach distances in patients with
      chronic ankle instability. Custom-molded with textured surface foot orthosis has
      a more pronounced effect compared with other foot orthoses. Clinical relevance
      The custom-molded foot orthosis with textured surface could be an effective
      device to improve dynamic balance in chronic ankle instability (CAI) patients. It
      may be considered as an efficient intervention to reduce ankle sprain recurrence
      in these individuals, although further research should be conducted.

PMID- 30101683
TI  - Vascular disease and aging in HIV: Time to extend the treatment cascade.

PMID- 30101684
TI  - Association of HIV infection with age and symptomatic carotid atherosclerotic
      disease at the time of carotid intervention in the United States.
AB  - The primary objectives of this work were: (1) to describe trends in HIV
      prevalence among those undergoing carotid intervention (carotid endarterectomy or
      carotid artery stenting) in the United States; and (2) to determine if HIV
      infection is independently associated with symptomatic carotid atherosclerotic
      disease or age at the time of carotid intervention. In a nationally
      representative inpatient database from 2004 to 2014, HIV infection was associated
      with younger age at the time of carotid intervention (59 years [SE 0.2] vs 71
      years [SE 0.01], p < 0.001), male sex (83% vs 58%, p < 0.001), black race (21% vs
      4%, p < 0.001), and symptomatic carotid atherosclerotic disease (18.8% vs 11.0%,
      p < 0.001). Among those undergoing carotid intervention, there was a significant
      increase in the prevalence of HIV from 0.08% in 2004 to 0.17% in 2014 ( p <
      0.001). After adjustment for patient demographics, comorbidities and other
      covariates, HIV infection remained significantly associated with younger age (
      8.9 years; 95% CI: -9.7 to -8.1; p < 0.001) at the time of carotid intervention,
      but HIV infection was not independently associated with symptomatic carotid
      atherosclerotic disease.

PMID- 30101686
TI  - 2018 Recognition and Awards.

PMID- 30101685
TI  - Psychophysiological response of different aircrew in normobaric hypoxia training.
AB  - Hypoxia remains the most important hazard in high altitude flights, but there is
      still a need for deeper analysis of the effect of hypoxia exposition in the
      psychophysiological and cognitive functions. The aim of this study was to study
      the effect of hypoxia training in cortical arousal, autonomic modulation, muscle
      strength and cognitive function. We analysed 23 male aircrew personnel of the
      Spanish Army and Air Force (10 Helicopter Pilots, 7 Transport Aircrew, 3
      Transport Pilots and 3 F-18 Fighter Pilots) before, during and after a normobaric
      hypoxia exposition. Hypoxia produced an increase in perceived stress and effort,
      a higher Heart Rate and a decreased function of breath muscles. Working memory
      and pattern recognition were impaired after hypoxia exposition. Significant
      differences were found in cognitive tests performance among aircrew groups,
      suggesting differences on their previous training. These results can improve
      specific training for better preparation of pilots and aircrews for hypoxic
      threats. Practitioner summary: Distinct aircrew preparation produces a different
      hypoxia exposition effect on psychophysiological response and cognitive
      functions. Hypoxia produced an increase in Heart Rate, a decreased function of
      breath muscles, being more negatively affected in Transport Pilots. Cognition
      abilities were impaired after hypoxia exposition, independently of the aircrew
      group.

PMID- 30101687
TI  - Building a Foundation for the Future.

PMID- 30101688
TI  - Introducing NASN's New Data Initiative: National School Health Data Set: Every
      Student Counts! Make This YOUR Year of Data.
AB  - The National Association of School Nurses (NASN) is launching a new data
      initiative: National School Health Data Set: Every Student Counts! This article
      describes the vision of the initiative, as well as what school nurses can do to
      advance a data-driven school health culture. This is the first article in a data
      and school nursing series for the 2018-2019 school year. For more information on
      NASN's initiative and to learn how school nurses can join the data revolution, go
      to http://nasn.org/everystudentcounts.

PMID- 30101689
TI  - Power of the Past, Celebrate the Present, Force of the Future Part 2: Our Story
      NASN's Second 25 Years.
AB  - The July 2018 issue of the NASN School Nurse, featured the first in a series of
      articles exploring the history, examining the present, and visioning the future
      of our organization in celebration of NASN's 50th anniversary. Part 2 of our
      historical account reflects on the leadership of a new generation of clinicians,
      reviewing the major emphases and accomplishments of NASN presidents serving from
      1993 to today.

PMID- 30101690
TI  - Catching the Data Vision.
AB  - As part of the "data and school-nursing" articles series, we will include an
      accompanying interview with practicing school nurses regarding the same topic and
      how it applies to the real life of school nurses. Our hope is that the practical
      application found in the interviews will provide readers with an increased
      understanding that will assist them on their own data journey.

PMID- 30101691
TI  - Microfluidic Flow Cell Array for Controlled Cell Deposition in Engineered
      Musculoskeletal Tissues.
AB  - Musculoskeletal tissues contain critical gradients in extracellular matrix (ECM)
      composition and cell types that allow for proper mechanical function of tissues
      and integration between adjacent tissues. However, properly controlling these
      patterns in engineered tissues is difficult and tissue engineering (TE) is
      presently in need of methods to generate integration zones for tissue anchoring,
      transition zones between tissues, and controlled ECM gradients for proper
      mechanical function. In this study, we present a novel method of using a
      microfluidic flow cell array (MFCA) to precisely control cell deposition onto TE
      constructs to produce tunable cell patterns on engineered constructs. In this
      study, we characterized MFCA cell deposition to efficiently and reliably deposit
      cells in controllable patterns and densities. We developed methods for deposition
      of human adipose-derived stem cells and human osteoblasts using a 12-channel
      pilot printhead. We mimicked key gradients and transitions by creating two-cell
      and three-cell-type transitions characteristic of the integration zones of
      musculoskeletal tissues. Overall, we demonstrate the ability to precisely and
      reproducibly control cell deposition on engineered constructs using this method
      and control cell population gradients. We establish the production of multicell
      transitions and multicell interfaces utilizing MFCA cell deposition, to
      demonstrate the potential of the method to create an extensive variety of
      engineered musculoskeletal tissues. Furthermore, customization of the printhead
      design can accommodate various structures, sizes, shapes, and number of flow cell
      channels to meet specific requirements for a broad range of musculoskeletal
      tissues.

PMID- 30101692
TI  - Example of two novel thiocyanato bridged copper (II) complexes derived from
      substituted thiosemicarbazone ligand: Structural elucidation, DNA/albumin
      binding, biological profile analysis and molecular docking study.
AB  - Two novel copper (II) substituted thiosemicarbazone Schiff base complexes
      [Cu(L1)(u-SCN)]n(NO3)2 (1) and [Cu2(u-SCN)(SCN)(L2)2](NO3) (2) have been
      synthesized by condensing substituted thiosemicarbazides like 4-methyl-3
      thiosemicarbazide or 4-ethyl-3-thiosemicarbazide with 2-acetylpyridine. Both the
      metal complexes 1 and 2 are characterized by different spectroscopic techniques
      like IR, UV-Vis, ESR spectroscopy followed by elemental analysis, cyclic
      voltammetric measurement and single crystal X-ray structure analysis. X-ray
      crystal structures of complex 1 and 2 reveal that complex 1 is polymeric while
      complex 2 is dimeric in nature. The coordination geometry around Cu(II) are
      square pyramidal in which thiosemicarbazone Schiff base ligand coordinate to the
      central Cu(II) atom in tridentate fashion. The prominent interaction patterns of
      1 and 2 with CT-DNA were examined by employing electronic absorption and emission
      spectral titrations, cyclic voltammetry and viscosity measurements. All the
      results show that CT-DNA binds with both copper (II) complexes 1 and 2. Further,
      protein binding ability in vitro of complexes 1 and 2 with both BSA and HSA were
      carried out by multispectroscopic techniques and a static quenching pattern was
      observed in both cases. Molecular docking study was employed to ascertain the
      exact mechanism of action of 1 and 2 with DNA and protein molecules (BSA and
      HSA). In vitro cytotoxicity activity of complexes 1 and 2 towards AGS and A549
      was evaluated by MTT assay which demonstrates that both complexes 1 and 2 have
      superior prospectus to act as anticancer agents.

PMID- 30101694
TI  - Urban metabolism as a key method to assess sustainability of cities.

PMID- 30101693
TI  - An ancient family of mobile genomic islands introducing cephalosporinase and
      carbapenemase genes in Enterobacteriaceae.
AB  - The exchange of mobile genomic islands (MGIs) between microorganisms is often
      mediated by phages, which may provide benefits to the phage's host. The present
      study started with the identification of Enterobacter cloacae, Klebsiella
      pneumoniae and Escherichia coli isolates with exceptional cephalosporin and
      carbapenem resistance phenotypes from patients in a neonatal ward. To identify
      possible molecular connections between these isolates and their beta-lactam
      resistance phenotypes, the respective bacterial genome sequences were compared.
      This unveiled the existence of a family of ancient MGIs that were probably
      exchanged before the species E. cloacae, K. pneumoniae and E. coli emerged from
      their common ancestry. A representative MGI from E. cloacae was named MIR17-GI,
      because it harbors the novel beta-lactamase gene variant blaMIR17. Importantly,
      our observations show that the MIR17-GI-like MGIs harbor genes associated with
      high-level resistance to cephalosporins. Among them, MIR17-GI stands out because
      MIR17 also displays carbapenemase activity. As shown by mass spectrometry, the
      MIR17 carbapenemase is among the most abundantly expressed proteins of the
      respective E. cloacae isolate. Further, we show that MIR17-GI-like islands are
      associated with integrated P4-like prophages. This implicates phages in the
      spread of cephalosporin and carbapenem resistance amongst Enterobacteriaceae. The
      discovery of an ancient family of MGIs, mediating the spread of cephalosporinase
      and carbapenemase genes, is of high clinical relevance, because high-level
      cephalosporin and carbapenem resistance have serious implications for the
      treatment of patients with enterobacteriaceal infections.

PMID- 30101695
TI  - The possible impact of hyperuricemia on serum soluble receptor for advanced
      glycation end products (sRAGE) levels in teenagers: a case control study.
AB  - Background Dietary advanced glycation end products (AGEs) and their interactions
      with the soluble receptors for AGEs (RAGE) play a crucial role in the
      pathogenesis of cardiovascular diseases. Objective This study was set out to
      assess, whether there was any association between serum sRAGE level and serum
      uric acid level in children with hyperuricemia Methods This case control study
      involved 53 patients (12 girls, 41 boys) with hyperuricemia (defined as serum
      uric acid >4.8 and >5.5 mg/dl in girls and boys, respectively) aged median of
      13.5-15.5 years. Thirty-six healthy individuals with normal serum uric acid level
      were selected as a reference group. Additionally the study group with
      hyperuricemia was divided into two groups: HU-HT (hypertensive n=25) and HU-NT
      (normotensive n=28) teenagers. The serum concentration of human sRAGE was
      measured using a commercially available enzyme-linked immunosorbent assay (ELISA)
      kit. Results We found statistically significant differences in serum sRAGE levels
      between normotensive subjects with hyperuricemia median: 169.8 pg/ml (Q1-Q3:148.3
      231.1 pg/ml) and reference group median: 129 pg/ml (Q1-Q3:107.4-175.3 pg/ml),
      p<0.01. Univariate analysis of the data revealed positive correlation between
      serum sRAGE and serum uric acid (r=0.306, p<0.05). Conclusion Our data showed
      that adolescents with an increased serum uric acid level had higher serum sRAGE
      levels. One of the possible explanation is of the oxidative stress, which plays
      an important role in pathogenesis of inflammation in patients with hyperuricemia.
      A question arises whether serum sRAGE might be a sensitive marker of inflammation
      process caused by hyperuricemia. Further studies are required to assess the
      relationship between sRAGE and markers of endothelial dysfunction.

PMID- 30101696
TI  - Redox sensitive polysaccharide based nanoparticles for improved cancer treatment:
      A comprehensive review.
AB  - BACKGROUND: Among the numerous bio-responsive polymeric drug delivery systems
      developed recently, redox-triggered release of molecular payloads have gained
      great deal of attention, especially in the field of anticancer drug delivery. In
      most cases, these systems rely on disulfide bonds located either in the matrix
      cross-link, or in auxiliary chains to achieve stimuli-responsive drug release.
      These bonds keep their stability in extracellular environments, yet, rapidly
      break by thiol-disulfide exchange reactions in the cytosol, due to the presence
      of greater levels of glutathione. Polysaccharides are macromolecules with low
      cost, natural abundance, biocompatibility, biodegradability, appropriate physical
      and chemical properties, and presence of numerous functional groups which
      facilitate chemical or physical cross-linking. METHODS: With regards to the
      remarkable advantages of polysaccharides, in the current study, various
      polysaccharide-based redox-responsive drug delivery systems are reviewed. In most
      cases the in vitro/in vivo effects of the developed system were also evaluated.
      RESULTS: Considering the hypoxic and reducing nature of the tumor
      microenvironment, with several folds higher glutathione levels than the systemic
      tissues, redox-sensitive polymeric systems could be implemented for tumor
      specific drug delivery and the results of previous researches in this field
      indicated satisfactory achievements. CONCLUSION: According to the reviewed
      papers, the efficiency of diverse redox-responsive polysaccharide-based
      nanoparticles with therapeutic payloads in cancer chemotherapy could be
      concluded. Nevertheless, more comprehensive studies are required to understand
      the exact intracellular and systemic fate of these nano-carriers, as well as
      their clinical efficacy for cancer treatment.

PMID- 30101697
TI  - The influence of silicone oil on the ganglion cell complex after pars plana
      vitrectomy for rhegmatogenous retinal detachment.
AB  - PURPOSE: Pars plana vitrectomy (PPV) and silicone oil endotamponade has been used
      as a treatment in rhegmatogenous retinal detachment (RRD). Improvement in the
      modality of spectral-domain optical coherence tomography (SD-OCT) allows for the
      assessment of ganglion cell layer-inner plexiform layer (GCL-IPL) in the macular
      region. Information about the GCL-IPL status may be a response to the question
      why the visual recovery after PPV with silicone oil tamponade is incomplete. The
      aim of the study was to evaluate the impact of silicone oil on GCL-IPL and
      compare it with other endotamponade types such as Sulfur hexafluoride gas (SF6),
      Perfluoropropane gas (C3F8) used during PPV performed due to RRD. PATIENTS AND
      METHODS: The study involved 57 eyes after PPV and 57 healthy, control eyes of
      patients with primary RRD who had undergone successful PPV. The patients were
      divided into three subgroups depending on the endotamponade type and were tracked
      with complete ophthalmological examination during a period of 6 months. PPV with
      internal tamponade silicone oil, 24% SF6 or 14% C3F8 was performed. The medical
      records were reviewed and compared between the groups. RESULTS: SD-OCT analysis
      detected a significant reduction of average GCL-IPL thickness and reduction of
      GCL-IPL parameter in almost all examined sectors in the group with silicone oil
      endotamponade during all follow-up visits (P<0.05). The study showed a
      significant vision deterioration in the silicone oil group in comparison with the
      SF6 group on all follow-up visits (P<0.05). CONCLUSION: This is the first in vivo
      SD-OCT study describing the toxic effect of silicone oil endotamponade on GCL-IPL
      complex after PPV for RRD. The study confirmed that GCL-IPL complex value can be
      a predictive factor for assessing the final visual acuity. SD-OCT should be
      recommended as a clinical standard in the follow-up treatment of patients after
      PPV for RRD, especially with the use of silicone oil endotamponade.

PMID- 30101698
TI  - Improvement of stability of tea polyphenols: a review.
AB  - Tea polyphenols have received much attention from the pharmaceutical and food
      industries owing to their extraordinary antioxidant and antibacterial
      characteristics. However, tea polyphenols are very unstable to processing and
      storage, since they are sensitive to the environmental factors like temperature,
      light and pH. Therefore, the effective application of tea polyphenols requires a
      protective mechanism to maintain its activity. The utilization of compounded tea
      polyphenols, instead of raw materials, can potentially help to improve their
      stability. This review focuses on the summarization of the compounding
      technologies for tea polyphenols, including physical technologies, chemical
      interfacial technologies and nano-scale compounding technologies. Of which, the
      emerging nanocellulose bio-carrier, as a promising technology, is particularly
      proposed.

PMID- 30101699
TI  - The Development of Pharmacophore Modeling: Generation and Recent Applications in
      Drug Discovery.
AB  - BACKGROUND: The pharmacophore concept in modern drug research is of great
      importance and promotes the development of drug industry as indicated by the
      number of publications available. METHODS: In this article, we reviewed and
      highlighted some successful examples about pharmacophore modeling, which was
      applied either in virtual screening for efficient hit discovery, or in the
      optimization of the lead compounds. Meanwhile, the analysis of some important
      aspects in pharmacophore modeling such as database, software was listed as well.
      RESULTS: Based on the analysis of these examples, we intended to provide an
      overview of pharmacophore-based virtual screening, which we hope to help readers
      gain insight into this powerful technique. CONCLUSIONS: Owing to its' convenience
      and efficiency, pharmacophore presents an essential method for drug discovery.

PMID- 30101700
TI  - Understanding the binding mechanism of Amyloid-beta inhibitors from molecular
      simulations.
AB  - In recent years, Abeta aggregation prevention, one of the most concerned
      strategies in drug development has been carefully assessed to treat Alzheimer's
      disease. Abeta peptides can transform structurally from random coil monomer into
      beta-stranded protofibril via multiple oligomeric states. Among the various Abeta
      species, the identification of binding targets has been challenging due to the
      heterogeneousity and metastable nature. A better understanding of Abeta species'
      assembly details and structural properties has been more characterized recently.
      Numerous potential inhibitors are identified that they can effectively bind on
      different Abeta species such as monomer, oligomer or protofibril during the
      inhibition of Abeta aggregation process. This review highlights the diversity of
      structural ensembles of Abeta species, from monomer to protofibril forms and the
      specific binding targets by their potential inhibitors. Comprehending the binding
      mechanism of Abeta inhibitors is indispensable for searching novel drug
      candidates against early-stage Alzheimer's disease.

PMID- 30101701
TI  - New Emerging Trends in Protein and Peptide Based Therapeutic Approaches - Part
      II.

PMID- 30101702
TI  - Chinese Herbal Medicine Hepatotoxicity: The Evaluation and Recognization Based on
      Large-scale Evidence Ddatabase.
AB  - This review summarizes the current research status of hepatotoxicity and points
      out that drug induced liver injury (DILI) remains an important scientific problem
      that urgently needs to be solved. Due to the special nature of Chinese Herbal
      medicine and the complexity of its clinical use, it is difficult to identify and
      evaluate its toxicity and resulting herb induced liver injury (HILI). At the same
      time, due to a lack of specific indicators, the direct and indirect long-term
      effects of Chinese Herbal Medicine on the liver are also difficult to be
      clinically determined. At present, the Roussel Uclaf Causality Assessment Method
      (RUCAM) is the most accepted method to evaluate DILI, but at present before using
      the RUCAM evaluation method, data resource collection and analysis are yet to be
      perfected. Based on existing research on drug-metabolizing enzymes mediating
      reactive metabolites (RMs), the aim of this study is to explore the possibilities
      and methods of building multidimensional hierarchical database composing of RMs
      evidence library, Chinese herbal evidence library, and individualized reports
      evidence library of herb induced liver injury HILI. First, the database would
      provide full profile of HILI from the basic ingredients to clinical outcomes by
      the most advanced algorithms of artificial intelligence, and it is also possible
      that we can predict possibilities of HILI after patients taking Chinese herbs by
      individual patient evaluation and prediction. Second, the database would solve
      the chaos and lack of the relevant data faced by the current basic research and
      clinical practice of Chinese Herbal Medicine. Third, we can also screen the
      susceptible patients from the database and thus prevent the accidents of HILI
      from the very beginning.

PMID- 30101703
TI  - Phytoconstituents and their possible mechanistic profile for Alzheimer's Disease 
      A Literature Review.
AB  - As the global aged population is increasing tremendously, time has come to
      concentrate on tail end life stage diseases. Alzheimer's disease (AD) is one such
      disease whose origin is an enigmatic, impacts later stage of life drastically due
      to irreparable damage of cognition. The characteristic feature of the disease is
      the accumulation of neurotoxic amyloid-beta (Abeta) and hyper phosphorylated Tau
      protein as fibrillary tangles. Several research reports obtained from in vitro
      and in vivo studies proved the efficacy of herbals in culminating
      neurodegenerative changes of AD by acting through various molecular pathways at
      various stages. So far some AChE inhibitors and NMDA receptor antagonists are the
      only approved medications and moreover western medicine is concentrating in
      isolation of moieties from the extracts that are responsible for therapeutic
      action. Even though several herbals have shown neuroprotective actions, we have
      mentioned about the phytoconstituents that have been tested experimentally
      against different Alzheimer's pathology models.

PMID- 30101704
TI  - Calcineurin Inhibition and Protein Kinase A Activation Limits Cognitive
      Dysfunction and Histopathological Damage in a Model of Dementia of the
      Alzheimer's Type.
AB  - AIM: The aim of the present work was to explore the outcome of combination of
      Calcineurin (CaN) inhibitor and Protein Kinase A (PKA) activator, in mouse models
      of experimental dementia. METHODS: Cognitive deficits were induced in mice by
      injecting Streptozotocin (STZ) intracerebroventricularly (i.c.v.); on the other
      hand aged animals were procured as a natural model of dementia. To assess
      cognitive function of mice Morris water maze (MWM) test was utilized; various
      biochemical studies and histopathological studies were also carried out. RESULTS:
      STZ injection and aging resulted in significant development of cognitive
      deficits; along-with enhancement of Myeloperoxidase (MPO) levels, Thiobarbituric
      Acid Reactive Species (TBARS), Acetylcholinestrase (AChE) activity, and reduced
      Glutathione (GSH) levels. Histopathological studies demonstrated pathological
      changes such as amyloid deposition and severe neutrophilic infiltration in brains
      of these mice. Donepezil /combination of Tacrolimus and Forskolin treatment
      markedly improve cognitive function, biochemical parameters, and
      histopathological alterations in STZ treated and aged mice. CONCLUSION: The
      outcome reveals that combination of CaN inhibitor and PKA activator has
      significantly alleviated memory dysfunction, biochemical alteration and
      histopathological changes quiet comparable to Donepezil. It has been inferred
      that combination of CaN and PKA can be served as an important target in dementia.

PMID- 30101705
TI  - MicroRNA-490-5P Targets CCND1 to Suppress Cellular Proliferation in Glioma Cells
      and Tissue Through Cell Cycle Arrest.
AB  - BACKGROUND: Glioma is a type of tumor that starts in the glial cells of brain and
      spine. However, the underlying molecular mechanisms of miRNAs dysregulation in
      glioma initiation and progression is largely unclear. OBJECTIVE: To further
      understand the molecular mechanism of miR-490-5P functions and how miR-490
      regulated CCND1 function. METHODS: The expression of miR-490-5P in glioma tissues
      and cells was measured by qRT-PCR and ISH. Cell transfection is responsible for
      miR-490-5P overexpression and knockdown. CCK-8 and clone formation assay are
      applicable to examine the capacity of glioma cells proliferation. Cell cycle
      analysis is used to test glioma cells cycle distribution with miR-490-5P
      overexpression or downregulation. Further, in vivo tumor exnograft studies are
      used to examine the effects of miR- 490-5P on glioma malignancy in vivo. RESULTS:
      We found overexpression of miR-490 lead to glioma cells cycle arrest at G1 phase
      and decreased proliferation. Next-step functional assays showed miR-490 regulated
      CCND1 expression and manipulated giloma cells proliferation. Finally, negative
      regulation of miR-490 in CCND1 function was validated through in vivo nude mice
      tumorigenesis assay and IHC examination in glioma tissue. CONCLUSION: Overall,
      these results showed that epigenetic regulation of CCND1 via miR-490 was
      essential to glioma and provide a new insight into glioma diagnosis, treatment,
      prognosis and further translational investigations.

PMID- 30101706
TI  - Probiotic Supplementation in Patients with Alzheimer's Dementia - An Explorative
      Intervention Study.
AB  - BACKGROUND: Dysbiosis of intestinal microbiota in the elderly can cause a leaky
      gut, which may result in silent systemic inflammation and promote
      neuroinflammation - a relevant pathomechanism in the early course of Alzheimer's
      disease. OBJECTIVE: The rebalancing of the microbiome could benefically impact on
      gut inflammation and immune activation. METHODS: In this study, routine
      laboratory tests in twenty outpatients (9 females, 11 males, aged 76.7 +/- 9.6
      years) with Alzheimer's disease were investigated. The mean Mini Mental State
      Examination score was 18.5 +/- 7.7. Biomarkers of immune activation - serum
      neopterin and tryptophan breakdown - as well as gut inflammation markers and
      microbiota composition in fecal specimens were analyzed in 18 patients before and
      after probiotic supplementation for 4 weeks. RESULTS: After treatment a decline
      of fecal zonulin concentrations and an increase in Faecalibacterium prausnitzii
      compared to baseline were observed. At the same time, serum kynurenine
      concentrations increased (p <0.05). Delta values (before - after) of neopterin
      and the kynurenine to tryptophan ratios (Kyn/Trp) correlated significantly (p
      <0.05). CONCLUSION: Results show that the supplementation of Alzheimer's disease
      patients with a multispecies probiotic influences gut bacteria composition as
      well as tryptophan metabolism in serum. The correlation between Kyn/Trp and
      neopterin concentrations points to the activation of macrophages and/or dendritic
      cells. Further studies are warranted to dissect the potential consequences of
      Probiotic supplementation in the course of Alzheimer's disease.

PMID- 30101707
TI  - Oral and Written Naming in Alzheimer's Disease: A Longitudinal Study.
AB  - BACKGROUND: The expressive difficulties in patients with Alzheimer's dementia
      have been extensively studied, mainly in oral language. However, the
      deterioration of their writing processes has received much less attention.
      OBJECTIVE: The present study aims to examine the decline of the performance of
      patients with Alzheimer's disease in both oral and written picture-naming tasks.
      METHOD: Sixty-four participants (half with Alzheimer's disease and half healthy
      elderly) were compared in the oral and written versions of a picture-naming task.
      Follow-up lasted two and a half years and patients were evaluated every six
      months. RESULTS: Cross-sectional data indicate that the controls performed better
      than the patients, and both groups showed a different pattern of errors. In terms
      of longitudinal data, the results show a similar pattern of deterioration in both
      tasks. In terms of errors, lexical-semantics were the most numerous at the
      beginning and their number remained constant throughout all evaluations. In the
      case of non-responses, there was a significant increase in the last session, both
      in oral and written naming. CONCLUSION: These results replicate those found in
      previous studies and highlight the utility of the naming task to detect minimal
      changes in the evolution of patients with Alzheimer's disease.

PMID- 30101708
TI  - Deformation-based Statistical Shape Analysis of the Corpus Callosum in Mild
      Cognitive Impairment and Alzheimer's Disease.
AB  - OBJECTIVE: In this study, we investigated the influence that the pathology of
      Alzheimer's disease (AD) exerts upon the corpus callosum (CC) using a total of
      325 mild cognitive impairment (MCI) subjects, 155 AD subjects, and 185 healthy
      control (HC) subjects. METHOD: Regionally-specific morphological CC
      abnormalities, as induced by AD, were quantified using a large deformation
      diffeomorphic metric curve mapping based statistical shape analysis pipeline. We
      also quantified the association between the CC shape phenotype and two cognitive
      measures; the Mini Mental State Examination (MMSE) and the Alzheimer's Disease
      Assessment Scale-Cognitive Behavior Section (ADAS-cog). To identify AD-relevant
      areas, CC was sub-divided into three subregions; the genu, body, and splenium
      (gCC, bCC, and sCC). RESULTS: We observed significant shape compressions in AD
      relative to that in HC, mainly concentrated on the superior part of CC, across
      all three sub-regions. The HC-vs-MCI shape abnormalities were also concentrated
      on the superior part, but mainly occurred on bCC and sCC. The significant MCI-vs
      AD shape differences, however, were only detected in part of sCC. In the shape
      cognition association, significant negative correlations to ADAS-cog were
      detected for shape deformations at regions belonging to gCC and sCC and
      significant positive correlations to MMSE at regions mainly belonging to sCC.
      CONCLUSION: Our results suggest that the callosal shape deformation patterns,
      especially those of sCC, linked tightly to the cognitive decline in AD, and are
      potentially a powerful biomarker for monitoring the progression of AD.

PMID- 30101709
TI  - Insights into the Drug Repositioning Applied to the Alzheimer's Disease Treatment
      and Future Perspectives.
AB  - INTRODUCTION: Alzheimer's disease is known to be a chronic disease, with an
      estimated prevalence of about 10-30%, considering the population over 60 years of
      age. Most patients with this disorder (> 95%) present the sporadic form, being
      characterized by a late onset (80-90 years of age), and it is the consequence of
      the failure to clear the amyloid-beta (Abeta) peptide from the interstices of the
      brain. Significant numbers of genetic risk factors for the sporadic disease have
      been researched. Some existing drugs for Alzheimer's disease provide symptomatic
      benefit for up to 12 months, but there are no approved disease- modifying
      therapies. In this line, a complementary strategy based on repositioning drugs
      which are approved for the treatment of other disorders could be interesting. It
      is noteworthy the fact that some clinical trials indicate that several classes of
      drugs own potent and beneficial effects on the Alzheimer's disease treatment. In
      this present work, we present the details and evaluation of these alternative
      treatments. It has highlighted several compounds with relevant evidence for this
      purpose, which deserves further investigation to clarify optimal treatment
      conditions in the clinical trials of patients with Alzheimer's disease.

PMID- 30101710
TI  - Ezrin Expression is Increased During Disease Progression in a Tauopathy Mouse
      Model and Alzheimer's Disease.
AB  - BACKGROUND: The lack of diagnostic tools and disease-modifying treatments against
      Alzheimer's disease (AD) and related disorders, collectively known as
      tauopathies, has led to a socioeconomic burden of epidemic proportion. Proteomics
      approaches can be used to identify novel proteome changes that could help us
      understand the pathogenesis of tau-related pathological hallmarks and/or cellular
      stress responses associated with tauopathy. These studies, however, need to be
      conducted taking into consideration brain region specificity and stage of
      neurodegeneration in order to provide insights about the pathological role of the
      identified proteins. METHODS: We used a tauopathy mouse model (JNPL3) that
      expresses human tau bearing a P301L mutation and develops motor impairment, the
      severity of which correlates with the increased accumulation of pathological tau.
      Tissue was dissected from asymptomatic and severely motor impaired JNPL3 mice as
      well as non-transgenic littermate controls and subjected to two-dimensional gel
      electrophoresis. Differentially abundant protein spots were identified by tandem
      mass spectrometry. Postmortem mild cognitive impairment (MCI), AD and normal
      aging controls were used to validate the pathological significance of the
      identified protein. RESULTS: Ezrin was identified as a protein that is
      upregulated in tau-mediated neurodegeneration. We demonstrate that Ezrin protein
      abundance increased in JNPL3 mice preceded motor impairment and was sustained in
      severely motor impaired mice. Ezrin expression was also increased in the temporal
      cortex of MCI and AD patients. CONCLUSION: The results demonstrate that increased
      Ezrin protein abundance changes are associated with the early stages of
      neurodegeneration in tauopathy models and human disease. Understanding the role
      of Ezrin in tauopathies such as AD may provide new insights for targeting tau
      mediated neurodegeneration.

PMID- 30101712
TI  - Structure-Based Drug Design Strategies and Challenges.
AB  - Over the past ten years, the number of three-dimensional protein structures
      identified by advanced science and technology increases, and the gene information
      becomes more available than ever before as well. The development of computing
      science becomes another driving force which makes it possible to use
      computational methods effectively in various phases of the drug design and
      research. Now Structure-Based Drug Design (SBDD) tools are widely used to help
      researchers to predict the position of small molecules within a three-dimensional
      representation of the protein structure and estimate the affinity of ligands to
      target protein with considerable accuracy and efficiency. They also accelerate
      discovery speed of potent drug and reduce the cost and times for drug research.
      Here we present an overview of SBDD used in drug discovery and highlight its
      recent successes and major challenges to current SBDD methodologies.

PMID- 30101713
TI  - Psychopharmacological treatment of Obsessive-Compulsive Disorder (OCD).
AB  - BACKGROUND: Obsessive-compulsive disorder (OCD) is associated with affective and
      cognitive symptoms causing personal distress and reduced global functioning.
      These have considerable societal costs due to healthcare service utilization.
      OBJECTIVE: Our aim was to assess the efficacy of pharmacological interventions in
      OCD and clinical guidelines, providing a comprehensive overview of this field.
      METHODS: We searched the PubMed database for papers dealing with drug treatment
      of OCD, with a specific focus on clinical guidelines, treatments with
      antidepressants, antipsychotics, mood stabilizers, off-label medications, and
      pharmacogenomics. RESULTS: Prolonged administration of selective serotonin
      reuptake inhibitors (SSRIs) is most effective. Better results can be obtained
      with a SSRI combined with cognitive behavioral therapy (CBT) or the similarly
      oriented exposure and response prevention (ERP). Refractory OCD could be treated
      with different strategies, including a switch to another SSRI or clomipramine, or
      augmentation with an atypical antipsychotic. The addition of medications other
      than antipsychotics or intravenous antidepressant administration needs further
      investigation, as the evidence is inconsistent. Pharmacogenomics and
      personalization of therapy could reduce treatment resistance. CONCLUSIONS:
      SSRI/clomipramine in combination with CBT/ERP is associated with the optimal
      response compared to each treatment alone or to other treatments. New strategies
      for refractory OCD are needed. The role of pharmacogenomics could become
      preponderant in the coming years.

PMID- 30101711
TI  - Analyzing of Molecular Networks for Human Diseases and Drug Discovery.
AB  - Molecular networks represent the interactions and relations of genes/proteins,
      and also encode molecular mechanisms of biological processes, development and
      diseases. Among the molecular networks, protein-protein Interaction Networks
      (PINs) have become effective platforms for uncovering the molecular mechanisms of
      diseases and drug discovery. PINs have been constructed for various organisms and
      utilized to solve many biological problems. In human, most proteins present their
      complex functions by interactions with other proteins, and the sum of these
      interactions represents the human protein interactome. Especially in the research
      on human disease and drugs, as an emerging tool, the PIN provides a platform to
      systematically explore the molecular complexities of specific diseases and the
      references for drug design. In this review, we summarized the commonly used
      approaches to aid disease research and drug discovery with PINs, including the
      network topological analysis, identification of novel pathways, drug targets and
      sub-network biomarkers for diseases. With the development of bioinformatic
      techniques and biological networks, PINs will play an increasingly important role
      in human disease research and drug discovery.

PMID- 30101714
TI  - School-based Prevention for Adolescent Internet Addiction: Prevention is the Key.
      A Systematic Literature Review.
AB  - Adolescents' media use represents a normative need for information,
      communication, recreation and functionality, yet problematic Internet use has
      increased. Given the arguably alarming prevalence rates worldwide and the
      increasingly problematic use of gaming and social media, the need for an
      integration of prevention efforts appears to be timely. The aim of this
      systematic literature review is (i) to identify school-based prevention
      programmes or protocols for Internet Addiction targeting adolescents within the
      school context and to examine the programmes' effectiveness, and (ii) to
      highlight strengths, limitations, and best practices to inform the design of new
      initiatives, by capitalizing on these studies' recommendations. The findings of
      the reviewed studies to date presented mixed outcomes and are in need of further
      empirical evidence. The current review identified the following needs to be
      addressed in future designs to: (i) define the clinical status of Internet
      Addiction more precisely, (ii) use more current psychometrically robust
      assessment tools for the measurement of effectiveness (based on the most recent
      empirical developments), (iii) reconsider the main outcome of Internet time
      reduction as it appears to be problematic, (iv) build methodologically sound
      evidence-based prevention programmes, (v) focus on skill enhancement and the use
      of protective and harm-reducing factors, and (vi) include IA as one of the risk
      behaviours in multi-risk behaviour interventions. These appear to be crucial
      factors in addressing future research designs and the formulation of new
      prevention initiatives. Validated findings could then inform promising strategies
      for IA and gaming prevention in public policy and education.

PMID- 30101715
TI  - Preterm Birth: Long Term Cardiovascular And Renal Consequences.
AB  - Cardiovascular and chronic kidney diseases are part of non-communicable chronic
      diseases, the leading causes of premature death worldwide. They are recognized as
      having early origins through altered developmental programming, due to adverse
      environmental conditions during development. Preterm birth is increasingly
      recognized as such an adverse factor. Rates of preterm birth have increased the
      last decades, however, with the improvement in perinatal and neonatal care, a
      growing cohort have survived to the neonatal period and are now entering
      adulthood. Clinical and experimental evidence suggests that preterm birth is
      associated with impaired or arrested structural or functional development of key
      organs/systems making preterm infants vulnerable to cardiovascular and chronic
      renal diseases at adulthood. This review analyzes the evidence of cardiovascular
      and renal changes, the role of perinatal and neonatal factors and potential
      pathogenic mechanisms, including developmental programming and epigenetic
      alterations. While antenatal steroids have considerably improved preterm birth
      outcomes, repeated therapy should be considered with caution, as antenatal
      steroids induce long term cardio-vascular and metabolic alterations in animals'
      models and their involvement in the accelerated cellular senescence observed in
      human studies cannot be excluded.

PMID- 30101716
TI  - Hormonal, Metabolic and Hemodynamic Adaptations to Glycosuria in Type 2 Diabetes
      Patients Treated with Sodium-Glucose Co-Transporter Inhibitors.
AB  - BACKGROUND & INTRODUCTION: The advent of the sodium-glucose cotransporter-2
      inhibitors [SGLT-2i] provides an additional tool to combat diabetes and
      complications. The use of SGLT-2i leads to effective and durable glycemic control
      with important reductions in body weight/fat and blood pressure. These agents may
      delay beta-cell deterioration and improve tissue insulin sensitivity, which might
      slow the progression of the disease. METHODS & RESULTS: In response to
      glycosuria, a compensatory rise in endogenous glucose production, sustained by a
      decrease in plasma insulin with an increase in glucagon has been described. Other
      possible mediators have been implicated and preliminary findings suggest that a
      sympathoadrenal discharge and/or rapid elevation in circulating substrates (i.e.,
      fatty acids) or some yet unidentified humoral factors may have a role in a renal
      hepatic inter-organ relationship. A possible contribution of enhanced renal
      gluconeogenesis to glucose entry into the systemic circulation has not yet been
      ruled out. Additionally, tissue glucose utilization decreases, whereas adipose
      tissue lipolysis is stimulated and, there is a switch to lipid oxidation with
      formation of ketone bodies; the risk for keto-acidosis may limit the use of SGLT
      2i. These metabolic adaptations are part of a counter-regulatory response to
      avoid hypoglycemia and, as a result, limit the SGLT-2i therapeutic efficacy.
      Recent trials revealed important cardiovascular [CV] beneficial effects of SGLT
      2i drugs when used in T2DM patients with CV disease. Although, the underlying
      mechanisms are not fully understood, there appears to be "class effect". Changes
      in hemodynamics and electrolyte/body fluid distribution are likely involved, but
      there is no evidence for anti-atherosclerotic effects. CONCLUSION: It is
      anticipated that, by providing durable diabetes control and reducing CV morbidity
      and mortality, the SGLT-2i class of drugs is destined to become a priority choice
      in diabetes management.

PMID- 30101717
TI  - Novel Tetrahydrobenzo [b] Thiophene Compounds Exhibit Anticancer Activity through
      Enhancing Apoptosis and Inhibiting Tyrosine Kinase.
AB  - : ackground: Developing new chemotherapeutic agents with molecular targets,
      larger margin of safety against normal cells and low cost is the target many
      scientists try to achieve. OBJECTIVE: The present study was undertaken to
      investigate the anticancer activity of a novel series of thiophene compounds and
      the molecular mechanisms associated. METHODS: A series of novel heterocyclic
      compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14, and
      15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9)
      was synthesized from 4,5,6,7-tetrahydrobenzo[b] thiophene (1). The newly
      synthesized derivatives along with the parent compound were evaluated for their
      anticancer activity against human HepG2, MCF7 and HCT116 cell lines and compared
      to doxorubicin as a reference drug. RESULTS: The compound 7 was very selective in
      targeting only the colon cells. Compounds 1, 5, and 12 showed strong cytotoxic
      activities against the 3 cell lines at 6-16 uM without any apparent toxicity to
      the normal fibroblasts WI-38. They had DNA affinity at 29-36 uM. The three
      compounds enhanced apoptosis to varying degrees elevating the expression of bax,
      caspase 9 and caspase 3 in HepG2. Compound 5 was the most potent analogue and was
      superior to the standard drug used in upregulating the apoptotic genes and
      inhibiting tyrosine kinase at 1 uM. The IC50 value for compound 5 against TK was
      296 nM. CONCLUSION: Taken together, this study presents some thiophene scaffolds
      as auspicious hits for further optimization as specific antiproliferative agents
      against cancer cells and promising tyrosine kinase inhibitors at nanomolar
      concentrations.

PMID- 30101719
TI  - A Mixture of Five Bacterial Strains Attenuates Skin Inflammation in Mice.
AB  - BACKGROUND: There is a growing interest in the effects of probiotics for the
      prevention and treatment of skin diseases due to their immunomodulatory and anti
      inflammatory properties. OBJECTIVE: To assess a mixture of five bacterial strains
      in the prevention of chronic skin inflammation in mice. METHOD: Hairless SKH-1
      mice received daily oral treatment with the probiotic mixture at the dose of
      1x109 colony-forming unit (CFU)/day (or vehicle) for three weeks. Chronic skin
      inflammation was induced by repeated applications of 12 O tetradecanoylphorbol-13
      acetate (TPA; control mice received acetone). Macroscopic and microscopic
      evaluations of skin lesions were performed and serum levels of interleukin (IL)
      1beta, IL-6, tumor necrosis factor (TNF)-alpha, IL 17, IL-22, IL-10 and IL-4
      measured at the end of study. RESULTS: Treatment with the probiotic mixture
      significantly limited the induced chronic skin inflammation at both the
      macroscopic and microscopic levels. This limitation was consistent with down
      regulated levels of pro-inflammatory cytokines (IL-1beta, IL-6, TNF-alpha, IL-17
      and IL-22) and up-regulated levels of the anti-inflammatory cytokines, IL-10 and
      IL-4. CONCLUSION: The results suggest that the probiotic mixture tested could
      help in preserving skin integrity and homeostasis, and that its use could be
      beneficial in dermatological conditions such as atopic dermatitis and psoriasis.

PMID- 30101718
TI  - Recent Advances in the Discovery of Novel Peptide Inhibitors Targeting 26S
      Proteasome.
AB  - BACKGROUND: The 26S proteasome is a proteolytic complex of multimeric protease,
      which operates at the executive end of the Ubiquitin-Proteasome System (UPS) and
      degrades the polyubiquitylated proteins Methods: After a brief introduction of
      26S proteasome and Ubiquitin-Proteasome System (UPS), this review focuses on the
      structure and function of the 26S proteasome in intracellular protein level
      regulation. Then, physiological regulation mechanisms and processes are
      elaborated. In addition, the advantages and defects of approved 26S proteasome
      inhibitors were discussed. Finally, we summarized the novel peptide 26S
      proteasome inhibitors according to their structural classifications, highlighting
      their design strategies, inhibitory activity and structure-activity relationships
      (SARs). RESULTS: Cellular function maintenance relies on the proteasome
      metabolizing intracellular proteins to control intracellular protein levels,
      which is especially important for cancer cells to survive and proliferate. In
      primary tumors, proteasomes had higher level and more potent activity. Currently,
      the approved small peptide inhibitors have proved their specific 26S proteasome
      inhibitory effects and considerable antitumor activities, but with obvious
      defects. Increasingly, novel peptide inhibitors are emerging and possess
      promising values in cancer therapy. CONCLUSION: Overall, the 26S proteasome is an
      efficient therapeutic target and novel 26S proteasome inhibitors hold potency for
      cancer therapy.

PMID- 30101720
TI  - Brain and Quantum Dots: Benefits of Nanotechnology for Healthy and Diseased
      Brain.
AB  - INTRODUCTION: The brain is the most complicated organ in a vertebrate's organism.
      In a human, it contains about two hundred billions of neurons and non-neuronal
      cells. To understand the mechanisms of the brain functions is the great challenge
      for the researchers. Much is already done on this way; however, it remains a lot
      to do still, and to get deeper knowledge, new approaches should be developed. One
      of this is to use benefits that nanotechnology brings in this area.
      Nanotechnology opens up unique opportunities, not only for material science
      research, but also for biology, medicine, and many other disciplines. There are
      several kinds of nanoparticles that can be applied in brain studies, quantum dots
      (QD) being so far most often used. QD are semiconductor light emitting
      nanocrystals with nanometer-sized structures of unique optical properties. They
      have bright fluorescence, are resistant to bleaching and able of emitting
      fluorescent light of different wavelengths. These properties make QD perfect
      tools for visualization of brain structures and mechanisms underlying its
      functions. Due to unique QD properties, even single molecules under study can be
      observed. Moreover QDs can be used for brain-targeted drug delivery. CONCLUSION:
      In this review, the application of quantum dots for the brain research is
      considered and benefits that it can bring are discussed.

PMID- 30101721
TI  - Ebola Therapeutic Study and Future Directions.
AB  - The constant Ebola epidemic outbreaks in Africa arisen waves of panic worldwide.
      There is a high mortality rate (30-70%) among Ebola infected people in virus
      stricken areas. Despite these horrors, the medical capabilities against this
      deadly viral disease were provided by limited therapeutic agents/options. As a
      result, several patented agents, biotherapies or prophylactic/therapeutic
      vaccines need to be reviving into the global markets-including patents of small
      molecular chemicals, short sequences or oligomers of DNA/RNA, linkages of
      chemicals with bio-molecules, herbal medicine and so on. In addition, the
      possible mechanisms of action of these therapeutic options are underway. To
      promote Ebola biomedical study, the multiple characters of Ebola infections-its
      origin, pathologic progresses, genomic changes, therapeutic context and economic
      considerations are outlined in this review. Finally a great difference can be
      expected after these types of efforts.

PMID- 30101722
TI  - Anticancer Mechanism of Lobaplatin as Monotherapy and in Combination with
      Paclitaxel in Human Gastric Cancer.
AB  - OBJECTIVE: To explore the mechanism by which lobaplatin, as monotherapy and in
      combination with paclitaxel, inhibits the proliferation of human gastric cancer
      SGC-7901 cells. METHODS: After treatment, the MTT assay was used to assess cell
      viability; cell cycle distribution was evaluated flow-cytometrically. Western
      blot was used to quantitate cyclin D1, E1, B1, and Cdk2/4 protein levels.
      RESULTS: Lobaplatin and paclitaxel inhibited SGC-7901 cell growth in a
      concentration and timedependent manner, with IC25 values at 48h of 1.97+/
      0.17ug/ml and 1.98+/-0.19 ng/ml, respectively. Interestingly, both drugs
      synergistically inhibited SGC-7901 cells (combination index [CI]<0.95).
      Lobaplatin did not affect cyclin D1 and CDK4 protein expression, while cyclin E1
      and CDK2 levels were significantly increased, with cyclin B1 amounts markedly
      decreased (p<0.05). More S phase cells were observed after lobaplatin treatment
      compared with controls (60.03+/-1.25 vs. 18.69+/-0.96%; p<0.05). After treatment
      with paclitaxel, cyclin D1 and CDK4 protein levels were similar to control
      values; meanwhile, cylinE1 and CDK2 protein amounts were reduced, with increased
      cyclin B1 levels, compared with control values (p<0.05). More G2/M cells were
      obtained after treatment with paclitaxel compared with control values (74.54+/
      0.92 vs. 18.62+/-0.44% (p<0.05). Lobaplatin and paclitaxel combination did not
      affect cyclin D1 and CDK4 protein levels (p>0.05); meanwhile, cyclin E1 and CDK2
      levels were increased, with reduced cyclin B1 amounts, compared with control
      values (p<0.05). Notably, more S (43.23+/-0.81 vs. 22.32+/-0.86%) and G2/M
      (31.22+/-0.96 vs. 25.81+/-2.08%) phase cells were obtained after combined
      treatment compared with control values. CONCLUSION: Lobaplatin and paclitaxel
      synergistically inhibit SGC-7901 cells.

PMID- 30101723
TI  - MicroRNAs in Preeclampsia.
AB  - Preeclampsia (PE) continues to represent a worldwide problem and challenge for
      both clinicians and laboratory-based doctors. Despite many efforts, the knowledge
      acquired regarding its pathogenesis and pathophysiology does not allow us to
      treat it efficiently. It is not possible to arrest its progressive nature, and
      the available therapies are limited to symptomatic treatment. Furthermore, both
      the diagnosis and prognosis are frequently uncertain, whilst the ability to
      predict its occurrence is very limited. MicroRNAs are small non-coding RNAs
      discovered two decades ago, and present great interest given their ability to
      regulate almost every aspect of the cell function. A lot of evidence regarding
      the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years.
      Differentially expressed miRNAs are characteristic of both mild and severe PE. In
      many cases they target signaling pathway-related genes that result in altered
      processes which are directly involved in PE. Immune system, angiogenesis and
      trophoblast proliferation and invasion, all fundamental aspects of placentation,
      are controlled in various degrees by miRNAs which are up- or downregulated.
      Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.

PMID- 30101724
TI  - Preparation of Chitosan Okra Nanoparticles: Optimization and Evaluation as
      Mucoadhesive Nasal Drug Delivery System.
AB  - OBJECTIVE: Esculin loaded nanoparticles for nasal delivery were prepared by ionic
      gelation technique using okra gum and chitosan Method: The preparation of
      nanoparticles was optimized using Box-Behnken experimental design employing
      particle size, entrapment efficiency and zeta potential as dependable variables.
      Okra concentration, chitosan concentration, pH and stirring speed were taken as
      independent variables. RESULTS: The formulations were found to depict particle
      size in the range of 294.0 to 613.4 nm. The concentration of gums was found to
      significantly influence the particle size and encapsulation efficiency. The
      nanoparticles were characterized by FTIR, SEM and TEM. The polyelectrolyte
      nanoparticles depicted bioadhesive strength of 32+/-2%. The in vitro drug release
      studies showed 96.4+/-4.2% release of esculin from nanoparticles in 4h. The drug
      release was found to follow the pattern of Hixson-Crowell release. CONCLUSION:
      The pharmacokinetic and biodistribution studies indicated sustained release of
      esculin and high brain targeting efficiency.

PMID- 30101725
TI  - Transethosomes Of Econazole Nitrate For Transdermal Delivery: Development, In
      Vitro Characterization, And Ex-Vivo Assessment.
AB  - BACKGROUND: Transdermal drug delivery is an attractive approach for both local
      and systemic therapeutics of various diseases. Transdermal drug delivery systems
      show various advantages like reduction of local irritation, prevention of first
      pass hepatic metabolism, and bioavailability enhancement of bioactive molecules
      over conventional drug delivery systems. OBJECTIVES: The main objective of the
      present research work was to develop and characterize (in-vitro and ex-vivo)
      econazole nitrate loaded transethosomes and their comparison with marketed cream
      of econazole nitrate [Ecoderm, Brown and Burk Pharmaceutical (Pvt.) Ltd.,
      Bengaluru, India] for effective transdermal delivery. METHODS: Transethosomes
      loaded with econazole nitrate were developed by homogenization method and
      evaluated for entrapment (%), vesicular size, zeta potential, polydispersity
      index (PDI), and in-vitro drug release. Furthermore, optimized econazole nitrate
      loaded transethosomes were added to Carbopol 934 gel and this gel was evaluated
      for viscosity, pH, drug content, ex-vivo skin permeation and retention studies
      followed by in-vitro antifungal activity against C. albicans fungus. RESULTS: The
      optimized transethosomes loaded with econazole nitrate showed vesicle size of
      159.3 +/- 4.3 nm, entrapment efficiency about 78.3 +/- 2.8%, acceptable colloidal
      properties like (zeta potential = -27.13 +/- 0.33 mV, PDI = 0.244 +/- 0.045),
      approximately 57.56 +/- 2.33% drug release upto 24 h. Results of DSC analysis
      confirmed encapsulation of econazole nitrate inside transethosomes. Optimized
      transethosomes showed drug release following zero order through diffusion
      mechanism. Transethosomal gel showed high drug content (92.35 +/- 0.63%) and
      acceptable values of pH (5.68 +/- 0.86) or viscosity (10390 +/- 111 cPs).
      Transethosomal gel showed less ex-vivo skin penetration (17.53 +/- 1.20%), high
      ex-vivo skin retention (38.75 +/- 2.88%), and high in-vitro antifungal activity
      compared to the marketed cream of econazole nitrate. CONCLUSION: Therefore, it
      can be concluded that econazole nitrate loaded transethosomes are effective to
      deliver econazole nitrate transdermally in a controlled fashion for effective
      elimination of cutaneous candidiasis.

PMID- 30101727
TI  - Prenatal exposure to an environmentally relevant mixture of Canadian Arctic
      contaminants decreases male reproductive function in an aging rat model.
AB  - Elevated levels of organochlorines (OC) have been reported in Inuit populations
      in the Arctic. We hypothesized that prenatal exposure to a Canadian Arctic OC
      mixture adversely affects male reproductive function and health with age. Sprague
      Dawley female rats (F0) were gavaged with an environmentally relevant
      concentration of an Arctic OC mixture or corn oil (Control) during mating with
      untreated males until parturition (F1 litters). After postnatal day (PND) 90, the
      weights of the OC F1 males differed dramatically relative to Controls (P<0.05;
      n=10) and they exhibited respiratory distress. Except for possible thinning of
      the alveolar barrier, histological observation of the lungs revealed no apparent
      pathology to explain the respiratory distress. At PND 365, OC F1 males had
      reduced relative reproductive organ weights and lower sperm quality than Controls
      (P<0.05). At PND 90, OC F1 males were subfertile (P<0.05), but were infertile at
      PND 365. In conclusion, environmentally relevant prenatal OC exposure reduced
      reproductive function and health in aging male rats, providing new insight into
      the effects of early-life exposures to these contaminants.

PMID- 30101726
TI  - Associations of the first occurrence of pathogen-specific clinical mastitis with
      milk yield and milk composition in dairy cows.
AB  - The aim of this study was to estimate the associations of the first occurrence of
      pathogen-specific clinical mastitis (CM) with milk yield and milk composition
      (somatic cell count (SCC), lactose, fat, protein content in milk and milk urea
      nitrogen (MUN)). We studied 3149 dairy cows in 31 Hokkaido dairy farms in Japan.
      Five pathogen groups were studied: Streptococcus spp.; Staphylococcus aureus (S.
      aureus); coagulase-negative staphylococci (CNS); coliforms; and fungi. Test-day
      milk data and clinical records were collected from June 2011 until February 2014.
      Mixed models with an autoregressive correlation structure were fitted to quantify
      the effects of CM and several other control variables (herd, calving season,
      parity, week of lactation, and other diseases). Primipara (first lactation) and
      multipara (second and later lactations) were analysed separately. All pathogens,
      particularly S. aureus and fungi, were associated with significant milk losses in
      multipara. In this study, S. aureus and CNS infections were not associated with
      significant milk loss in primipara. All pathogens, in particular S. aureus and
      fungi, significantly increased SCC in both parity groups. All pathogens,
      especially CNS (in primipara) and S. aureus (in multipara), decreased lactose
      content. All pathogen groups except for fungi were associated with significant
      changes in fat, protein and MUN. Some pathogens such as Streptococcus spp. and
      coliforms seemed to be associated with long-term fat, protein and MUN changes.
      These findings provide estimates that could be used to calculate precise costs of
      CM, and also provide better indicators of pathogen-specific mastitis.

PMID- 30101728
TI  - Reading and writing the scientific voyage: FitzRoy, Darwin and John Clunies Ross.
AB  - An unpublished satirical work, written c.1848-1854, provides fresh insight into
      the most famous scientific voyage of the nineteenth century. John Clunies Ross,
      settler of Cocos-Keeling - which HMS Beagle visited in April 1836 - felt that
      Robert FitzRoy and Charles Darwin had 'depreciated' the atoll on which he and his
      family had settled a decade earlier. Producing a mock 'supplement' to a new
      edition of FitzRoy's Narrative, Ross criticized their science and their casual
      appropriation of local knowledge. Ross's virtually unknown work is intriguing not
      only for its glimpse of the Beagle voyage, but also as a self-portrait of an
      imperial scientific reader. An experienced merchant seaman and trader
      entrepreneur with decades of experience in the region, Ross had a very different
      perspective from that of FitzRoy or Darwin. Yet he shared many of their
      assumptions about the importance of natural knowledge, embracing it as part of
      his own imperial projects. Showing the global reach of print culture, he used
      editing and revision as satirical weapons, insisting on his right to participate
      as both reader and author in scientific debate.

PMID- 30101729
TI  - Potential of using synthesized nano-zeolite for ammonium and phosphate
      immobilization in dairy wastewater.
AB  - The studies described in the Research Communication aimed to describe the
      feasibility of using coal fly ash to synthesize nano-zeolite, and the ammonium
      and phosphate adsorption efficiencies of the nanomaterial in dairy wastewater.
      Chemical treatment of coal fly ash was conducted and changes observed. Samples
      treated with NaOH had an increased cation exchange capacity and P sorption index
      compared to the initial fly ash, due to particle modification from smooth surface
      to plate- and rod-shape crystals, referred to as nano-zeolite. Batch experiments
      were conducted by mixing coal fly ash and nano-zeolite with synthesized
      wastewater to study the effect of sorption time, pH values and dosage of nano
      zeolite on ammonium and phosphate removal efficiency. The adsorption process
      reached equilibrium in a very short time (less than 60 min), which suggests a
      potential for fast immobilization of pollutants. The concentration of ammonium
      decreased from 118 to 35 mg/l (71% removal) while the concentration of phosphate
      decreased from 52 to 45 mg/l. The removal efficiency of ammonium was 36.6, 51.8
      and 70.9% at pH 3, 7 and 10, respectively whilst that of phosphate increased
      dramatically with decreased slurry pH (92.1, 47.3 and 12.3% at pH 3, 7 and 10,
      respectively). Nano-zeolite could be a potential absorbent for fast
      immobilization of ammonium but not phosphate. Surface modification of nano
      zeolite could be introduced in order to enhance the pollutants removal
      efficiency.

PMID- 30101730
TI  - Promoting access to fresh fruits and vegetables through a local market
      intervention at a subway station.
AB  - OBJECTIVE: Alternative food sources (AFS) such as local markets in disadvantaged
      areas are promising strategies for preventing chronic disease and reducing health
      inequalities. The present study assessed how sociodemographic characteristics,
      physical access and fruit and vegetable (F&V) consumption are associated with
      market use in a newly opened F&V market next to a subway station in a
      disadvantaged neighbourhood. DESIGN: Two cross-sectional surveys were conducted
      among adults: (i) on-site, among shoppers who had just bought F&V and (ii) a
      telephone-based population survey among residents living within 1 km distance
      from the market. SETTING: One neighbourhood in Montreal (Canada) with previously
      limited F&V offerings. SUBJECTS: Respectively, 218 shoppers and 335 residents
      completed the on-site and telephone-based population surveys. RESULTS: Among
      shoppers, 23 % were low-income, 56 % did not consume enough F&V and 54 % did not
      have access to a car. Among all participants living 1 km from the market (n 472),
      market usage was associated (OR; 95 % CI) with adequate F&V consumption (1.86;
      1.10, 3.16), living closer to the market (for distance: 0.86; 0.76, 0.97), having
      the market on the commute route (2.77; 1.61, 4.75) and not having access to a car
      (2.96; 1.67, 5.26). CONCLUSIONS: When implemented in strategic locations such as
      transport hubs, AFS like F&V markets offer a promising strategy to improve F&V
      access among populations that may be constrained in their food acquisition
      practices, including low-income populations and those relying on public
      transportation.

PMID- 30101732
TI  - Effect of fermentation temperature and different Streptococcus thermophilus to
      Lactobacillus bulgaricus ratios on Kermanshahi roghan and yoghurt fatty acid
      profiles.
AB  - The objective of the study reported in this Research Communication was to
      investigate the effect of fermentation temperature (37 and 45  degrees C) and
      different ratios of Streptococcus thermophilus to Lactobacillus bulgaricus (3 :
      1, 1 : 1 and 1 : 3) on Kermanshahi roghan and yoghurt fatty acid profiles (FAP)
      in order to obtain a product with optimized fatty acid profiles. Kermanshahi
      roghan is a yoghurt by-product in western Iran (Kermanshah). The results revealed
      that incubation temperature at 37  degrees C as compared to 45  degrees C had a
      better effect on fatty acid profiles of roghan and yoghurt. Furthermore, the
      results showed that fatty acid profile of roghan is better than yoghurt at two
      experimental temperatures. On the other hand, the roghan products made by equal
      ratio of S. thermophilus and L. bulgaricus (1 : 1) had the best quality of fatty
      acid profiles. Although a lower incubation temperature increases incubation time,
      our finding suggests that inoculation ratio 1 : 1 at 37  degrees C as compared to
      45  degrees C can affect the quality of roghan and yoghurt fatty acid profiles.

PMID- 30101731
TI  - LifeLab Southampton: a programme to engage adolescents with DOHaD concepts as a
      tool for increasing health literacy in teenagers -a pilot cluster-randomized
      control trial.
AB  - Adolescence is a critical time point in the lifecourse. LifeLab is an educational
      intervention engaging adolescents in understanding Developmental Origins of
      Health and Disease (DOHaD) concepts and the impact of the early life environment
      on future health, benefitting both their long-term health and that of the next
      generation. We aimed to assess whether engaging adolescents with DOHaD concepts
      improves scientific literacy and whether engagement alone improves health
      behaviours.Six schools were randomized, three to intervention and three to
      control. Outcome measures were changed in knowledge, and intended and actual
      behaviour in relation to diet and lifestyle. A total of 333 students completed
      baseline and follow-up questionnaires. At 12 months, intervention students showed
      greater understanding of DOHaD concepts. No sustained changes in behaviours were
      identified.Adolescents' engagement with DOHaD concepts can be improved and
      maintained over 12 months. Such engagement does not itself translate into
      behaviour change. The intervention has consequently been revised to include
      additional components beyond engagement alone.

PMID- 30101733
TI  - A mixed-methods evaluation using low-income adult Georgians' experience with a
      smartphone-based eLearning nutrition education programme.
AB  - OBJECTIVE: To understand low-income adults' expectations and experiences using an
      innovative smartphone and theory-based eLearning nutrition education programme,
      entitled Food eTalk. DESIGN: Longitudinal mixed-methods single case study
      including a series of focus group and individual interviews, demographic and
      Internet habits surveys, and user-tracking data. Interviews were transcribed
      verbatim, analysed using the constant comparative method and digitalized using
      Atlas.ti. Descriptive statistics were analysed for demographics and user-tracking
      data. SETTING: Community-based locations including libraries, public housing
      complexes, schools, safety-net clinics and food pantries. SUBJECTS: Low-income
      Georgian adults aged >=18 years (n 64), USA. RESULTS: Participants found Food
      eTalk easy to navigate and better designed than expected. Primary themes were
      twofold: (i) motivation to engage in eLearning may be a formidable barrier to
      Food eTalk's success but improved programme content, format and external
      incentives could mitigate this barrier; and (ii) applying knowledge to change
      nutrition-related behaviour is challenging. To encourage engagement in eLearning
      nutrition education, programme format should highlight interactive games, videos,
      be short in length, and feature content that is relevant and important from the
      perspective of the priority audience. Examples of these topics include quick and
      easy recipes, chronic disease-specific diet information and tips to feed 'picky'
      children. Additionally, external incentives may help mitigate barriers to
      healthful eating behaviour and increase engagement in the programme. CONCLUSIONS:
      The findings suggest eLearning nutrition education programmes are best designed
      to match low-income adults' typical smartphone habits, include content considered
      particularly relevant by the intended audience and highlight solutions to
      barriers to healthful eating.

PMID- 30101734
TI  - Treatment outcomes for anorexia nervosa: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: To determine the impact of specialized treatments, relative to
      comparator treatments, upon the weight and psychological symptoms of anorexia
      nervosa (AN) at end-of-treatment (EOT) and follow-up. METHODS: Randomized
      controlled trials (RCTs) between January 1980 and December 2017 that reported the
      effects of at least two treatments on AN were screened. Weight and psychological
      symptoms were analyzed separately for each study. PRISMA (Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses) guidelines were followed, and
      studies were assessed using the GRADE (Grading of Recommendations, Assessment,
      Development and Evaluation) criteria and Cochrane risk of bias tool. RESULTS: We
      identified 35 eligible RCTs, comprising data from 2524 patients. Meta-analyses
      revealed a significant treatment effect on weight outcomes at EOT [g = 0.16, 95%
      CI (0.05-0.28), p = 0.006], but not at follow-up [g = 0.11, 95% CI (-0.04 to
      0.27), p = 0.15]. There was no significant treatment effect on psychological
      outcomes at either EOT [g = -0.03, 95% CI (-0.14 to 0.08), p = 0.63], or follow
      up [g = -0.001, 95% CI (-0.11 to 0.11), p = 0.98]. There was no strong evidence
      of publication bias or significant moderator effects for illness duration, mean
      age, year of publication, comparator group category, or risk of bias (all p
      values > 0.05). CONCLUSIONS: Current specialized treatments are more adept than
      comparator interventions at imparting change in weight-based AN symptoms at EOT,
      but not at follow-up. Specialized treatments confer no advantage over comparator
      interventions in terms of psychological symptoms. Future precision treatment
      efforts require a specific focus on the psychological symptoms of AN.

PMID- 30101735
TI  - Determinants of treatment of mental disorders in Lebanon: barriers to treatment
      and changing patterns of service use.
AB  - : AimsTo investigate for the first time the determinants and barriers of seeking
      help for mental disorders in the Arab world based on a national study: Lebanese
      Evaluation of the Burden of Ailments and Needs Of the Nation (L.E.B.A.N.O.N).
      METHODS: A nationally representative (n = 2857) and multistage clustered area
      probability household sample of adults >=18 years and older was assessed for
      lifetime and 12 months mental disorders using the Composite International
      Diagnostic Interview. In addition, detailed information was obtained on help-
      seeking behaviour and barriers to treatment. RESULTS: In total, 19.7% of the
      Lebanese with mental disorders sought any type of treatment: 91% of those who
      sought treatment did so within the health sector. Severity and perceived severity
      of disorders predicted seeking help, the highest being for panic disorder. The
      greatest barrier to seek help was low perceived need for treatment (73.9%).
      Stigma was reported to be a factor only in 5.9% of those who thought about
      seeking treatment. Eighty per cent of the Lebanese reported they would not be
      embarrassed if friends knew they were seeking help from a professional.
      CONCLUSIONS: A small fraction of Lebanese seek help for their mental health
      problems: female gender, higher education and income are predictors of positive
      attitudes to help seeking. Severity and recognition of disorders, more than
      stigma, to get treatment seem to be the most important factors in determining
      help seeking. The findings underscore the importance of helping the public
      recognise mental health disorders.

PMID- 30101736
TI  - Population DNA methylation studies in the Developmental Origins of Health and
      Disease (DOHaD) framework.
AB  - Epigenetic changes represent a potential mechanism underlying associations of
      early-life exposures and later life health outcomes. Population-based cohort
      studies starting in early life are an attractive framework to study the role of
      such changes. DNA methylation is the most studied epigenetic mechanism in
      population research. We discuss the application of DNA methylation in early-life
      population studies, some recent findings, key challenges and recommendations for
      future research. Studies into DNA methylation within the Developmental Origins of
      Health and Disease framework generally either explore associations between
      prenatal exposures and offspring DNA methylation or associations between
      offspring DNA methylation in early life and later health outcomes. Only a few
      studies to date have integrated prospective exposure, epigenetic and phenotypic
      data in order to explicitly test the role of DNA methylation as a potential
      biological mediator of environmental effects on health outcomes. Population
      epigenetics is an emerging field which has challenges in terms of methodology and
      interpretation of the data. Key challenges include tissue specificity, cell type
      adjustment, issues of power and comparability of findings, genetic influences,
      and exploring causality and functional consequences. Ongoing studies are working
      on addressing these issues. Large collaborative efforts of prospective cohorts
      are emerging, with clear benefits in terms of optimizing power and use of
      resources, and in advancing methodology. In the future, multidisciplinary
      approaches, within and beyond longitudinal birth and preconception cohorts will
      advance this complex, but highly promising, the field of research.

PMID- 30101737
TI  - DSM outcomes of psychotic experiences and associated risk factors: 6-year follow
      up study in a community-based sample.
AB  - BACKGROUND: Psychotic experiences (PEs) may predict a range of common, non
      psychotic disorders as well as psychotic disorders. In this representative,
      general population-based cohort study, both psychotic and non-psychotic disorder
      outcomes of PE were analysed, as were potential moderators. METHODS: Addresses
      were contacted in a multistage clustered probability sampling frame covering 11
      districts and 302 neighbourhoods at baseline (n = 4011). Participants were
      interviewed with the Composite International Diagnostic Interview (CIDI) both at
      baseline and at 6-year follow-up. Participants with PE at baseline were
      clinically re-interviewed with the SCID-I at follow-up. The role of socio
      demographics, characteristics of PE, co-occurrence of mood disorders and family
      history of mental disorders were tested in the association between baseline PE
      and follow-up diagnosis. RESULTS: In the participants with baseline PE, the
      psychotic disorder diagnosis rate at follow up was 7.0% - much lower than the
      rates of DSM-IV mood disorders without psychotic features (42.8%) and other non
      psychotic disorders (24.1%). Within the group with baseline PE, female sex, lower
      socio-economic status, co-occurrence of mood disorders, family history of a
      mental disorder and persistence of PE predicted any follow-up DSM diagnosis.
      Furthermore, onset of psychotic v. non-psychotic disorder was predicted by
      younger age (15-30 years), co-presence of delusional and hallucinatory PE and
      family history of severe mental illness. CONCLUSION: The outcome of PE appears to
      be a consequence of baseline severity of multidimensional psychopathology and
      familial risk. It may be useful to consider PE as a risk indicator that has trans
      diagnostic value.

PMID- 30101738
TI  - Psychometric Properties of the Spanish Short Depressive Rumination Scale in a
      Nonclinical Sample.
AB  - Repetitive negative thinking (RNT) is considered a transdiagnostic variable
      underlying common symptoms (e.g., depressed mood) across various mood disorders.
      Depressive rumination is one typical and frequent manifestation of RNT and is a
      well-known vulnerability factor of depression onset, maintenance and recurrence.
      Due to the time-related constraints in assessment settings and the association of
      rumination on sadness with diagnosis of depression, the rapid identification of
      individuals scoring high on this construct may become a useful screening tool in
      non-clinical samples. The main aim of the present study was to test the
      psychometric properties of the Spanish version of the Short Depressive Rumination
      Scale (SDRS) in a large sample (N = 649). Confirmatory Factor Analysis supported
      a one-factor model accounting for 75% of variance with an excellent internal
      consistency (alpha = .93) in spite of the reduced number of items (4 items).
      Criterion validity results based on associations with other well-established
      rumination (sub)scales, age, scores in depression and gender differences, were
      congruent. The results suggest that the SDRS, the shortest existing scale
      assessing depressive rumination to our knowledge, can be a useful instrument for
      a rapid assessment of depressive rumination in community samples.

PMID- 30101739
TI  - Letter to the Editor.

PMID- 30101740
TI  - Antimicrobial Resistance in Acinetobacter spp. and Pseudomonas spp.
AB  - The nonfermenting bacteria belonging to Acinetobacter spp. and Pseudomonas spp.
      are capable of colonizing both humans and animals and can also be opportunistic
      pathogens. More specifically, the species Acinetobacter baumannii and Pseudomonas
      aeruginosa have been recurrently reported as multidrug-resistant and even pandrug
      resistant in clinical isolates. Both species were categorized among the ESKAPE
      pathogens, ESKAPE standing for Enterococcus faecium, Staphylococcus aureus,
      Klebsiella pneumoniae, A. baumannii, P. aeruginosa, and Enterobacter species.
      These six pathogens are the major cause of nosocomial infections in the United
      States and are a threat all over the world because of their capacity to become
      increasingly resistant to all available antibiotics. A. baumannii and P.
      aeruginosa are both intrinsically resistant to many antibiotics due to
      complementary mechanisms, the main ones being the low permeability of their outer
      membrane, the production of the AmpC beta-lactamase, and the production of
      several efflux systems belonging to the resistance-nodulation-cell division
      family. In addition, they are both capable of acquiring multiple resistance
      determinants, such as beta-lactamases or carbapenemases. Even if such enzymes
      have rarely been identified in bacteria of animal origin, they may sooner or
      later spread to this reservoir. The goal of this article is to give an overview
      of the resistance phenotypes described in these pathogens and to provide a
      comprehensive analysis of all data that have been reported on Acinetobacter spp.
      and Pseudomonas spp. from animal hosts.

PMID- 30101741
TI  - Depression is reduced by physical activity, but there's a limit, finds study.

PMID- 30101743
TI  - The scourge of avoidable neonatal mortality in Malawi.

PMID- 30101742
TI  - Is the world ready for the next pandemic threat?

PMID- 30101744
TI  - Global epidemics: how well can we cope?

PMID- 30101745
TI  - One in seven children born to mothers who had Zika infection has health problems.

PMID- 30101746
TI  - Argentinian senators reject bill to legalise abortion.

PMID- 30101747
TI  - HPV vaccine safety: Cochrane launches urgent investigation into review after
      criticisms.

PMID- 30101748
TI  - Sudden cardiac deaths: one-off screening misses cardiomyopathies in young
      footballers.

PMID- 30101749
TI  - Clinical trial transparency in the Americas: the need to coordinate regulatory
      spheres.

PMID- 30101750
TI  - Self-adaptive ultrasonic beam amplifiers: application to transcostal shock wave
      therapy.
AB  - Ultrasound shock wave therapy is increasingly used for non-invasive surgery. It
      requires the focusing of very high pressure amplitude in precisely controlled
      focal spots. In transcostal therapy of the heart or the liver, the high impedance
      mismatch between the bones and surrounding tissues gives rise to strong
      aberrations and attenuation of the therapeutic wavefront, with potential risks of
      injury at the tissue-bone interface. An adaptive propagation of the ultrasonic
      beam through the intercostal spaces would be required. Several solutions have
      been developed so far, but they require a prior knowledge of the patient's
      anatomy or an invasive calibration process, not applicable in clinic. Here, we
      develop a non-invasive adaptive focusing method for ultrasound therapy through
      the ribcage using a time reversal cavity (TRC) acting as an ultrasonic beam
      amplifier. This method is based on ribcage imaging through the TRC and a
      projection orthogonally to the strongest identified reflectors. The focal
      pressure of our device was improved by up to 30% using such self-adaptive
      processing, without degrading the focal spots size and shape. This improvement
      allowed lesion formation in an Ultracal(r) phantom through a ribcage without
      invasive calibration of the device. This adaptive method could be particularly
      interesting to improve the efficiency and the safety of pulsed cavitational
      therapy of the heart or the liver.

PMID- 30101751
TI  - Ionization chamber dosimetry based on 60Co absorbed dose to water calibration for
      diagnostic kilovoltage x-ray beams.
AB  - The purpose of this study was to develop a new ionization chamber dosimetry
      formalism for diagnostic kilovoltage x-ray beams based on a 60Co absorbed dose-to
      water calibration coefficient [Formula: see text]. To validate the new chamber
      dosimetry, 39 fluence spectra of kilovoltage x-rays were calculated, using a
      SpekCalc program, for Al half-value-layer (Al-HVL) values of 1.4-8.5 mm and tube
      voltages of 50-137.6 kVp. We used these spectra to calculate the beam quality
      conversion factor [Formula: see text] for kilovoltage x-ray beams Q x to a 60Co
      beam for a PTW 30013 Farmer(r) ionization chamber in a reference geometrical
      setup (depth  =  1 cm in water, field size  =  20  *  20 cm2). The absorbed dose
      to water for kilovoltage x-rays was obtained using [Formula: see text] and
      [Formula: see text]. Meanwhile, the water surface dose based on the air kerma
      calibration coefficient N K was obtained using a Monte Carlo-calculated
      correction factor CF (corresponding to [Formula: see text] in AAPM TG-61) for the
      39 x-ray fluence spectra. The absorbed dose based on [Formula: see text] was
      validated by comparing the water surface dose for the 39 x-ray fluence spectra
      with the water surface dose based on N K . The water surface dose based on
      [Formula: see text] was obtained using Monte Carlo-calculated percentage depth
      doses. For Al-HVL ranging from 1.4 to 8.5 mm, [Formula: see text] ranged from
      0.884 to 0.956 and CF ranged from 1.264 to 1.663. The water surface dose based on
      [Formula: see text] for the x-ray fluence spectra was 1.0% higher on average than
      that based on N K , except for Al-HVLs of 1.4 and 1.5 mm and 1% was within their
      uncertainty ranges. Therefore, it is possible to use the absorbed dose-to-water
      value based on [Formula: see text] instead of on N K . With the new chamber
      dosimetry, the chamber reading can be easily converted to the absorbed dose using
      [Formula: see text] and the calculated [Formula: see text].

PMID- 30101752
TI  - Discussing the high frequency intrinsic permeability of nanostructures using
      first order reversal curves.
AB  - First order reversal curves (FORC) and intrinsic high frequency permeability
      spectra have been simulated and analyzed for '1 * 3' iron nanowire (NW) arrays
      with different interwire distances (D). Discrete interaction constants are found
      and gradually disappeared with increasing D value. The number of weak resonance
      peaks decreases with increasing D value. Two strong resonance peaks are found for
      each array with different D values: the lower one is ascribed to the 'edge mode'.
      The higher one is ascribed to the 'bulk mode'. The magnetic loss due to the edge
      mode cannot be neglected. The difference in bulk mode resonance in the simulated
      and the calculated are believed to arise from the interaction between NWs. It is
      believed that the local effective magnetic fields determine the orientation of
      magnetic moments in the equilibrium states, and consequently determine the high
      frequency intrinsic permeability spectra. FORC diagrams are helpful to reveal the
      distribution of local coercive fields.

PMID- 30101753
TI  - Genetic-based feature selection for efficient motion imaging of a brain-computer
      interface framework.
AB  - OBJECTIVE: A brain-computer interface (BCI) equips humans with the ability to
      control computers and technical devices mentally. However, the enormous data and
      the existing irrelevant features of the electrocorticogram signal limit the
      performance of the classifier. To address these problems, a novel signal
      processing framework for a binary motor imagery-based BCI system (MI-BCI) is
      proposed in this paper. APPROACH: Stockwell transform and Bayesian linear
      discriminant analysis were applied to feature extraction and classification,
      respectively, and a genetic algorithm (GA) was used in the process of feature
      selection to extract the most relevant features for classification. The
      superiority of the algorithm is demonstrated through test results based on the
      BCI Competition III dataset I. MAIN RESULTS: By comparing the processes with or
      without feature selection, the performance of the classification was proven to
      improve using the GA. By adjusting the parameters of the GA, the best feature set
      (selected 48.6% features) was selected to achieve classification sensitivity,
      specificity, precision, and accuracy of 94%, 98%, 97.9%, and 96%, respectively,
      exceeding the results of the existing state-of-the art algorithms. SIGNIFICANCE:
      As the proposed method can reduce the number of features and select the best
      feature set, its classification performance was improved and the classification
      time was shortened; thus, it can be applied to various BCI systems.

PMID- 30101754
TI  - The Multigaussian method: a new approach to mitigating spatial heterogeneities
      with multichannel radiochromic film dosimetry.
AB  - The main objective of multichannel radiochromic film dosimetry methods is to
      correct, or at least mitigate, spatial heterogeneities in the film-scanner
      response, especially variations in the active layer thickness. To this end, films
      can also be scanned prior to irradiation. In this study, the abilities of various
      single channel and multichannel methods to reduce spatial heterogeneities, with
      and without scanning before irradiation, were tested. Red, green and blue single
      channel models, two additive channel independent perturbation (CHIP) models and
      two multiplicative CHIP models were compared with the Multigaussian method. The
      Multigaussian method is a new approach to multichannel dosimetry, based on
      experimental findings. It assumes that the probability density function of the
      response vector formed by the pixel values of the different color channels,
      including irradiated and non-irradiated scans, follows a multivariate Gaussian
      distribution. The Multigaussian method provided more accurate doses than the
      other models under comparison, especially when incorporating the information of
      the film prior to irradiation. The relative dose differences between reference
      doses measured with MatriXX and film doses were examined. After applying inter
      scan and lateral corrections, the lowest mean absolute errors were 0.8% and 1.0%
      for the Multigaussian method with and without the information of the scan before
      irradiation, respectively. Followed by the uniform multiplicative CHIP and red
      single channel models, using pixel values and net optical density, respectively,
      both with 1.1%.

PMID- 30101755
TI  - Direct observation of leakage currents in a metal-insulator-metal capacitor using
      in situ transmission electron microscopy.
AB  - With the acceleration of the scaling down of integrated circuits, it has become
      very challenging to fabricate a metal-insulator-metal (MIM) capacitor with a high
      capacitance density and low leakage current for nanoscale dynamic random access
      memory. Yttria-stabilized-zirconia (YSZ) thin films, one of the insulators in the
      constitution of MIM capacitors, have been reported to have various crystal
      structures from the monoclinic phase to the cubic phase according to different Y
      doping levels. The electrical characteristics depend on the crystal structure of
      the YSZ thin film. Here, we report the local crystallization of YSZ thin films
      via Joule heating and the leakage current induced during in situ transmission
      electron microscopy biasing tests. We studied the crystallization process and the
      increase in the leakage current using experimental and simulation results. It is
      important to understand the relationship between the crystallinity and electrical
      properties of YSZ thin films in MIM capacitors.

PMID- 30101756
TI  - Coronary artery calcium quantification using contrast-enhanced dual-energy
      computed tomography scans in comparison with unenhanced single-energy scans.
AB  - Extracting coronary artery calcium (CAC) scores from contrast-enhanced computed
      tomography (CT) images using dual-energy (DE) based material decomposition has
      been shown feasible, mainly through patient studies. However, the quantitative
      performance of such DE-based CAC scores, particularly per stenosis, is
      underexamined due to lack of reference standard and repeated scans. In this work
      we conducted a comprehensive quantitative comparative analysis of CAC scores
      obtained with DE and compare to conventional unenhanced single-energy (SE) CT
      scans through phantom studies. Synthetic vessels filled with iodinated blood
      mimicking material and containing calcium stenoses of different sizes and
      densities were scanned with a third generation dual-source CT scanner in a chest
      phantom using a DE coronary CT angiography protocol with three exposures/CTDIvol:
      auto-mAs/8 mGy (automatic exposure), 160 mAs/20 mGy and 260 mAs/34 mGy and 10
      repeats. As a control, a set of vessel phantoms without iodine was scanned using
      a standard SE CAC score protocol (3 mGy). Calcium volume, mass and Agatston
      scores were estimated for each stenosis. For DE dataset, image-based three
      material decomposition was applied to remove iodine before scoring. Performance
      of DE-based calcium scores were analyzed on a per-stenosis level and compared to
      SE-based scores. There was excellent correlation between the DE- and SE-based
      scores (correlation coefficient r: 0.92-0.98). Percent bias for the calcium
      volume and mass scores varied as a function of stenosis size and density for both
      modalities. Precision (coefficient of variation) improved with larger and denser
      stenoses for both DE- and SE-based calcium scores. DE-based scores (20 mGy and 34
      mGy) provided comparable per-stenosis precision to SE-based (3 mGy). Our findings
      suggest that on a per-stenosis level, DE-based CAC scores from contrast-enhanced
      CT images can achieve comparable quantification performance to conventional SE
      based scores. However, DE-based CAC scoring required more dose compared with SE
      for high per-stenosis precision so some caution is necessary with clinical DE
      based CAC scoring.

PMID- 30101757
TI  - An excitation emission fluorescence lifetime spectrometer using a frequency
      doubled supercontinuum laser source.
AB  - The accurate fluorescence analysis of complex, multi-fluorophore containing
      proteins requires the use of multi-dimensional measurement techniques. For the
      measurement of intrinsic fluorescence from tyrosine (Tyr) and tryptophan (Trp)
      one needs tuneable UV excitation and for steady-state measurements like
      Excitation Emission Matrix (EEM) simple pulsed Xe lamps are commonly used.
      Unfortunately, simultaneous multi-dimensional wavelength and time resolved
      measurement of intrinsic protein fluorescence in the 260 to 400 nm spectral range
      are challenging and typically required the use of very complex tuneable laser
      systems or multiple single excitation wavelength sources. Here we have assembled
      and validated a novel Excitation Emission Fluorescence Lifetime Spectrometer
      (EEFLS) using a pulsed, frequency doubled, Super-Continuum Laser (SCL) source
      coupled with a 16 channel multi-anode Time Correlated Single Photon Counting
      (TCSPC) measurement system. This EEFLS enabled the collection of near complete
      lifetime and intensity maps over the most important intrinsic protein
      fluorescence spectral range (lambda ex = 260-350/lambda em = 300-500 nm). The 4
      dimensional (lambda ex/lambda em/I(t)/tau) Excitation Emission Fluorescence
      Lifetime Matrix (EEFLM) data produced can be used to better characterize the
      complex intrinsic emission from proteins. The system was capable of measuring
      fluorescence emission data with high spectral (1-2 nm) resolution and had an
      Instrument Response Function (IRF) of ~650 ps for accurate measurement of
      nanosecond lifetimes. UV power output was stable after a warm up period, with
      variations of <2% over 9 hours and reproducible (relative standard deviation RSD
      < 1.5%). This enabled the collection of accurate EEFLM data at low resolution
      (~12 nm in excitation and emission) in 1-2 hours or high resolution (4 nm) in ~17
      hours. EEFLS performance in the UV was compared with a conventional commercial
      TCSPC system using pulsed LED excitation and validated using solutions of p
      terphenyl and tryptophan.

PMID- 30101758
TI  - Characterization of a binary system composed of luminescent quantum dots for
      liquid scintillation.
AB  - Scintillation dosimetry has evolved towards utilizing 3D liquid dosimeters to
      perform quality assurance verification of complex treatment configuration for
      photon, electron and proton beams. However, most of the fluorophores utilized in
      these dosimeters are alike and present limitations. This study aims to establish
      the profile of CdSe colloidal quantum dots (cQDs) that were given the role of the
      fluorophore in a binary liquid scintillation system. We chose to investigate the
      cQDs because of their wide absorption spectrum, the tunability of their
      absorption and emission spectra with respect to their size and composition, and
      their ability to function as an effective energy transfer intermediate. The
      scintillation intensity and spectral response of three organic solvent-based
      liquid cQD dispersions have been investigated upon irradiation with kV and MV
      photon beams. The solvents used to disperse the cQDs were hexane, toluene and
      linear alkylbenzene. The scintillation efficiency of the cQD dispersions has
      proven to be dependent on the nature of the solvent, the alkylbenzene cQD liquid
      dispersion having the brightest light emission of the three solutions, for an
      equivalent deposited dose in the scintillator. Its light output was found to
      reach a tenth of the light intensity of a commercial liquid scintillator, Ultima
      Gold, irradiated under the same conditions. This cQD dispersion also demonstrated
      a remarkable energy transfer to the cQDs, only 5% of its intensity being due to
      Cherenkov light production in the solvent. Overall, these results indicate that
      the alkylbenzene cQD liquid dispersion could be the best choice for a potential
      cQD-based liquid scintillator.

PMID- 30101759
TI  - Application of plastic scintillating fibres to surface dosimetry in megavoltage
      photon and electron beams: considerations for Cerenkov correction.
AB  - This work investigated the application of plastic scintillation detectors (PSDs)
      in dosimetry measurements on the surface of a phantom in megavoltage photon and
      electron beams. Emission spectra associated with fluorescence in the PMMA optical
      fibre, Cerenkov in the optical fibre, and the signal from the scintillator were
      characterized with a spectrophotometer. The angular dependence of the PSD
      response was studied with the PSD both in the plane and perpendicular to the
      plane of gantry rotation. Two methods of stem correction were investigated: stem
      subtraction and full spectral correction. It was found that with the PSD in the
      plane of gantry rotation, the stem subtraction method overestimates the dose
      particularly in electrons. The magnitude of overestimation is dependent on the
      beam energy, scintillator type and the angle of incidence. In this study a
      maximum error of 12% was observed for 16 MeV with a gantry angle of 45 degrees .
      It was shown that the cause of this error was a non-negligible emission of
      Cerenkov radiation from the scintillator itself. This error was not observed when
      the PSD was oriented perpendicular to the plane of rotation. Similarly, the full
      spectral method was effective in isolating the scintillation-only signal
      regardless of PSD orientation.

PMID- 30101760
TI  - Enhanced settling in activated sludge: design and operation considerations.
AB  - Settling of activated sludge particles has long been the key to successfully
      achieving secondary treatment. While soluble products can be converted to
      particulate components via microbial reactions in the activated sludge process,
      it is the subsequent removal of these particulate components that is the key to
      achieving ultimate water quality criteria. An understanding of the operating
      parameters for selecting good settling activated sludge particles was first
      documented in the 1970s and 1980s. An understanding of the growth pressures that
      can be imposed on filamentous organisms, and the impacts of selector zones in
      general, allowed the design and operation of activated sludge processes to
      routinely achieve good sludge settleability. More recently, research has
      identified what could be the next evolution in flocculant growth, with the
      growing interest in aerobic granular sludge. Aerobic granular sludge is purported
      to provide superior settling properties, and many of the growth pressures
      identified for aerobic granular sludge are also present in activated sludge
      systems. These enhanced settling sludge systems are gaining significant interest,
      but the factors leading to enhanced sludge settleability could be present in
      historical and existing systems. Three facilities were evaluated that exhibited
      enhanced settleability (i.e. sludge volume indices of less than 70 mL/g the
      majority of the time) to determine how these enhanced settling sludges compare to
      typical settling curves from the literature. The enhanced settling sludge
      facilities exhibit key differences related to surface overflow rate, return
      activated sludge (RAS) pumping requirements, and sensitivity to solids
      concentration that are critical for developing effective settling designs for
      enhanced settling sludge facilities. As more facilities aim to achieve enhanced
      settling sludge for intensification of infrastructure, it will be important to
      carefully consider historic settling curves and to develop site-specific settling
      criteria when possible.

PMID- 30101761
TI  - Dimensioning of vortex storm overflows.
AB  - Vortex storm overflow is an interesting and useful technical solution, especially
      important in storm and combined sewage systems. However, there are no methods of
      this device dimensioning, which would be mathematically simple and properly
      precise physically. Such a method has been proposed in this paper, on the basis
      of investigations performed for the vortex separators and vortex flow controls.
      The essence of this method relies on the kinematic model of the velocity field
      and energy balance of the inflowing stream and dissipation. The procedure enables
      specialists to calculate the rise of the liquid free surface caused by the inlet
      stream energy and the hydraulic resistance of the bottom outlet. These
      mathematical relations are completed by two formulae: for the bottom 'morning
      glory' sink and for the upper overflow. The model has been positively verified
      during the laboratory measurements, so can be used during the technical
      dimensioning of the vortex storm overflows.

PMID- 30101762
TI  - Ozonation of nursing home wastewater pretreated in a membrane bioreactor.
AB  - Nursing home (NH) wastewater was pretreated in an ultrafiltration membrane
      bioreactor (MBR) and subsequently ozonated in a pilot plant in order to evaluate
      the elimination of pharmaceutically active compounds (PhACs). Dosing of the pre
      treated wastewater with 5 mg ozone (O3) L-1 led to the elimination of >50% for
      nearly all investigated PhACs in the ozonation plant, whereas dosing 10 mg O3 L-1
      increased elimination to >80%. A total hydraulic retention time of 12.8 min
      proved sufficient for PhAC elimination. Specific ozone consumption and influent
      dissolved organic carbon (DOC) (8.2-9.5 mg L-1) were in similar ranges for all
      three performed trials. Combining the MBR with subsequent ozonation at a dosage
      of 5 mg O3 L-1 achieved elimination of >90% and effluent concentrations below 250
      ng L-1 for nearly all the investigated PhACs. Influent concentrations of the MBR
      were comparable to those found in municipal wastewater. Thus, the recommended
      dosage for PhAC elimination of 5 mg O3 L-1 (i.e. a specific consumption of 0.6 g
      O3*(g DOC)-1) is in the same range as for municipal wastewater. However, due to a
      smaller plant size, the specific costs for treating NH wastewater would
      significantly exceed those of treating municipal wastewater.

PMID- 30101763
TI  - Coffee processing industrial wastewater treatment using batch electrochemical
      coagulation with stainless steel and Fe electrodes and their combinations, and
      recovery and reuse of sludge.
AB  - The efficiency of chemical oxygen demand (COD) and color removal from raw coffee
      processing wastewater (CPWW) using batch electrochemical coagulation (BECC)
      treatment process using stainless steel (SS) and iron (Fe) electrode combinations
      are investigated. Of the combinations: four SS, four Fe, Fe-Fe-SS-SS, Fe-SS-Fe
      SS, SS-SS-Fe-Fe, and SS-Fe-SS-Fe; four SS electrodes operated at 23 V having 120
      A/m2 current density was found as a good operating condition to achieve ~87% COD
      removal from its initial COD of 1,984 mg/L and corresponding color removal of
      97.1% (initial color 7,000 PCU). The second best electrode combination, SS-SS-Fe
      Fe, had COD and color removals of 75% and 91%. When using polyaluminum chloride
      (PAC) as aid with different dosages of 20-100 mg/L, 50 mg/L PAC showed maximum
      COD and color removals of 80% and 92%. Comparison of proximate and ultimate
      analyses of various solid fuels with CPWW ECC sludge showed its usefulness as a
      soil supplement and as an adsorbent for reutilization. The solid residue obtained
      after BECC was characterized using energy dispersive X-ray spectroscopy and other
      analyses. Summarizing the results, it was concluded that BECC can be effectively
      used for maximum removal of organics from raw CPWW with clean water reclamations
      of up to ~90% using ECC as a novel treatment technique.

PMID- 30101764
TI  - Mechanistic studies on the biosorption of Pb(II) by Pseudomonas aeruginosa.
AB  - The biosorption of Pb(II) ions from aqueous solution has been studied using both
      the intact and thermolyzed cells of Pseudomonas aeruginosa. Further, the role of
      the major cell wall components, namely DNA, protein, polysaccharide, and lipid,
      in Pb(II) binding has been assessed using an enzymatic treatment method. The
      Pb(II) bioremediation capability of P. aeruginosa cells has been investigated by
      varying the parameters of pH, time of interaction, amount of biomass, and
      concentration of Pb(II). The complete bioremoval of Pb(II) using intact cells has
      been achieved for an initial Pb(II) concentration of 12.4 mg L-1 at pH 6.2 and
      temperature 29 +/- 1  degrees C. The biosorption isotherm follows Langmuirian
      behavior with a Gibbs free energy of -30.7 kJ mol-1, indicative of chemisorption.
      The biosorption kinetics is consistent with a pseudo-second-order model. The
      possible Pb(II) binding mechanisms of P. aeruginosa cells are discussed based on
      characterization using zeta potential measurements, Fourier transform infra-red
      spectroscopy, and energy dispersive X-ray spectroscopy. The results confirm that
      among the major cell wall components studied, polysaccharide shows the highest
      contribution towards Pb(II) binding, followed by DNA, lipid, and protein. Similar
      studies using thermolyzed cells show higher Pb(II) uptake compared to the intact
      cells both before and after enzymatic treatment.

PMID- 30101765
TI  - Biological fuel cells produce bioelectricity with in-situ brackish water
      purification.
AB  - Biological fuel cells, namely microbial desalination cells (MDCs) are a promising
      alternative to traditional desalination technologies, as microorganisms can
      convert the energy stored in wastewater directly into electricity and utilize it
      in situ to drive desalination, producing a high-quality reuse water. However,
      there are several challenges to be overcome in order to scale up from laboratory
      research. This study was conducted in order to better understand the performance
      of MDCs inoculated with marine sediments during the treatment of brackish water
      (5.0 g L-1 of NaCl) under three different configurations and cycles of
      desalination, envisaging the future treatment of saline wastewaters with
      conductivities lower than 10 mS cm-1. Results have shown that by increasing the
      desalination cycle three times, the efficiency of salt removal was improved by
      3.4, 2.4 and 2.3 times for 1-MDC, 3-MDC, and 5-MDC, respectively. The same trend
      was observed for electrochemical data. Findings encourage further development of
      the MDC for sustainable brackish water and wastewater purification and future on
      site utilization.

PMID- 30101766
TI  - On-line chemical oxygen demand estimation models for the photoelectrocatalytic
      oxidation advanced treatment of papermaking wastewater.
AB  - Chemical oxygen demand (COD), an important indicative measure of the amount of
      oxidizable pollutants in wastewater, is often analyzed off-line due to the
      expensive sensor required for on-line analysis. However, its off-line analysis is
      time-consuming. An on-line COD estimation method was developed with
      photoelectrocatalytic (PEC) technology. Based on the on-line data of the
      oxidation-reduction potential (ORP), dissolved oxygen (DO) and pH of wastewater,
      four different artificial neural network methods were applied to develop working
      models for COD estimation. Six different batches of sequence batch reactor (SBR)
      effluent from a paper mill were treated with PEC oxidation for 90 minutes, and
      546 data points were collected from the on-line measurements of ORP, DO and pH,
      and the off-line COD analysis. After having training and validation with 75% and
      25% of data, and evaluation with four statistical criteria (R2, RMSE, MAE and
      MAPE), the estimation results indicated that the developed radial basis neural
      network (RBNN) model demonstrated the highest precision. Subsequently, the
      application of the RBNN model to a new batch of SBR effluent from the paper mill
      revealed that the RBNN model was acceptable for COD estimation during the PEC
      advanced treatment process of papermaking wastewater, which implied its possible
      application in the future.

PMID- 30101767
TI  - Bacterial species diversity as an indicator of dibromonitrilopropionamide (DBNPA)
      biocide efficacy.
AB  - Microorganism growth in industrial systems is controlled through the use of
      biocides and biodispersants. There is, however, no simple means of determining
      the efficacy of these control mechanisms, but it is currently tested using
      complex bacterial culturing techniques. Biolog Ecoplates(r) have been used to
      detect bacterial population changes in various communities. These microtitre
      plates comprise 31 different carbon substrates (in triplicate) with wells. When a
      sample is added to the wells, bacteria capable of metabolising the relevant
      carbon sources respire the substrates, causing the tetrazolium dye in the well to
      turn purple, indicating a positive result. Hypothetically, the higher the
      microbial diversity, the more substrates will be utilised and vice versa. The
      objective of this study was to test this hypothesis, using Biolog Ecoplates(r) as
      a potential simple indicator to determine the efficiency of a biocide to control
      microbial growth in cooling water systems by monitoring the changes in the
      microbial metabolic pattern. This study proved the hypothesis using Biolog
      Ecoplates(r), indicating that the addition of biocides at various concentrations
      resulted in fewer substrates being utilised, indicative of a decrease in
      microbial species diversity.

PMID- 30101768
TI  - Nitrogen removal and N2O emission by shunt distributing wastewater in aerated or
      non-aerated subsurface wastewater infiltration systems under different shunt
      ratios.
AB  - This study investigated matrix oxidation-reduction potential (ORP), nitrogen
      removal, N2O emission and nitrogen removal functional gene abundance in three
      subsurface wastewater infiltration systems (SWISs), named SWIS A (without
      aeration or shunt distributing wastewater), SWIS B (with shunt distributing
      wastewater) and SWIS C (with intermittent aeration and shunt distributing
      wastewater) under different shunt ratios. Aerobic conditions were produced at a
      depth of 50 cm and anoxic or anaerobic conditions were not changed at depths of
      80 and 110 cm by aeration in SWIS C. High average removal rates of chemical
      oxygen demand (COD) (83.1% for SWIS B, 90.9% for SWIS C), NH3-N (74.3% for SWIS
      B, 90.8% for SWIS C) and total nitrogen (TN) (61.1% for SWIS B, 87.9% for SWIS C)
      were obtained under shunt ratios of 1:3 and 1:2 for SWIS B and C, respectively.
      The lowest N2O emission rate (28.4 mg/(m2 d)) and highest nitrogen removal
      functional gene abundances were achieved in SWIS C under a 1:2 shunt ratio. The
      results suggested intermittent aeration and shunt distributing wastewater
      combined strategy would enhance nitrogen removal and reduce N2O emission for
      SWISs.

PMID- 30101769
TI  - Promotion of catalytic ozonation of aniline with Mn-Ce-Ox/gamma-Al2O3.
AB  - In this study, Mn-Ce-Ox/gamma-Al2O3 supported catalysts were adopted to promote
      the removal efficiency of aniline in simulated wastewater with ozone. Mn-Ce
      Ox/gamma-Al2O3 catalysts were prepared by the impregnation-calcination method.
      Its phase structure, specific surface area, loading amount and distribution of
      active units were analyzed by XRD, BET, ICP-AES and TEM/SEM respectively. The
      characterization results demonstrated that the catalysts had a good dispersion of
      Mn-Ce-Ox active sites and an abundant porous structure from the gamma-Al2O3
      support. The catalytic ozonation results showed that with Mn3-Ce1-Ox/gamma
      Al2O3(1.0), the aniline removal efficiency was highly improved, 15.0% higher than
      that of ozonation without a catalyst. Furthermore, from the variation in loading
      amounts of Mn and Ce, it can be seen that the molar ratio of Mn and Ce within the
      Mn-Ce-Ox plays a key role in accelerating the ozonation of aniline in simulated
      wastewater with ozone, while Mn:Ce = 1.9:1 showed the best performance. More
      importantly, the catalysts showed high recycling performance and could be reused
      at least 12 times without obvious loss of activity.

PMID- 30101770
TI  - Does influent COD/N ratio affect nitrogen removal and N2O emission in a novel
      biochar-sludge amended soil wastewater infiltration system (SWIS)?
AB  - Nitrogen removal and N2O emission of a biochar-sludge amended soil wastewater
      infiltration system (SWIS) with/without intermittent aeration under different
      influent COD/N ratios was investigated. Nitrogen removal and N2O emission were
      affected by influent COD/N ratio. Under a COD/N ratio between 1:1 and 15:1,
      average chemical oxygen demand (COD), NH4+-N and total nitrogen (TN) removal
      rates decreased with COD/N ratio increase in non-aerated SWISs amended
      with/without biochar-sludge; an increasing COD/N ratio hardly affected COD and
      NH4+-N removal in a biochar-sludge amended SWIS with intermittent aeration; the
      N2O emission rate decreased with COD/N ratio increase in the studied SWISs. The
      biochar-sludge amended SWIS with intermittent aeration achieved high COD (92.2%),
      NH4+-N (96.8%), and TN (92.7%) removal rates and a low N2O emission rate (10.6
      mg/(m2 d)) under a COD/N ratio of 15:1, which was higher than those in non
      aerated SWISs amended with/without biochar-sludge. Combining the biochar-sludge
      amended SWIS with intermittent aeration enhanced the number of nitrifying
      bacteria, denitrifying bacteria, nitrate reductase activities, nitrite reductase
      activities, and improved the abundance of nitrogen removal functional genes under
      a high influent COD/N ratio. The results suggested that the joint use of
      intermittent aeration and biochar-sludge in a SWIS could be an effective and
      appropriate strategy for improving nitrogen removal and reducing N2O emissions in
      treating high COD/N ratio wastewater.

PMID- 30101771
TI  - Selection of quorum quenching (QQ) bacteria for membrane biofouling control:
      effect of different Gram-staining QQ bacteria, Bacillus sp. T5 and Delftia sp.
      T6, on microbial population in membrane bioreactors.
AB  - This study aimed to address the gap in understanding how the microbial community
      present within quorum quenching-membrane bioreactor (QQ-MBRs) changes during the
      operations by investigating the behavior of two different types of QQ bacteria,
      Bacillus sp. T5 and Delftia sp. T6. The anti-biofouling effects of T5 and T6 in
      the QQ-MBR were 85% and 76%, respectively. According to the Illumina HiSeq
      results, when the QQ-MBR was operated with Gram-positive bacteria, T5, in the
      mixed liquor a reduction was observed in Gram-positive bacteria and Gram-negative
      bacteria population increased. In contrast, when the QQ-MBR was operated with
      Gram-negative bacteria, T6, Gram-negative bacteria population reduced and an
      increase in Gram-positive bacteria observed. As such, the outputs of the Illumina
      analysis revealed that use of Gram-negative QQ bacteria in the reactor induced a
      Gram-positive microbial community and vice versa. This indicates that a close
      interaction occurs between indigenous Gram-negative and positive bacterial phyla,
      and Bacillus sp. T5/Delftia sp. T6 is fundamental to the performance of MBRs.
      This is the first study demonstrating such a relationship and assistance
      selecting QQ bacteria/strategy in an effective way.

PMID- 30101772
TI  - Zero-valent iron nanoparticles for methylene blue removal from aqueous solutions
      and textile wastewater treatment, with cost estimation.
AB  - Nanoscale zero-valent iron (nZVI) particles were investigated for the removal of
      methylene blue (MB) from aqueous solutions and the treatment of textile industry
      effluents. The nZVI material was characterized by XRD, TEM, EDS, FTIR, and SEM.
      It was demonstrated that several functional groups such as C-H, C = C, C-C, and C
      O contributed to MB reduction. At initial MB concentration of 70 mg/L, the
      optimum pH was 6, achieving a removal efficiency of 72.1% using an nZVI dosage of
      10 g/L, stirring rate of 150 rpm, and temperature of 30  degrees C within 30 min.
      The adsorption isotherm was described by the Langmuir model with monolayer
      coverage of 5.53 mg/g, and the Freundlich equation with multilayer adsorption
      capacity of 1.59 (mg/g).(L/mg)1/n. The removal mechanisms of MB included
      reduction into colorless leuco-MB, precipitation as Fe(II)-MB, adsorption as ZVI
      MB or FeOOH-MB, and/or degradation using *OH radicals. The synthesized nZVI
      particles were applied to reduce various organic and inorganic compounds, as well
      as heavy metal ions from real textile wastewater samples. The removal
      efficiencies of COD, BOD, TN, TP, Cu2+, Zn2+, and Pb2+ reached up to 91.9%,
      87.5%, 65.2%, 78.1%, 100.0%, 29.6%, and 99.0%, respectively. The treatment cost
      of 1 m3 of textile wastewater was estimated as 1.66 $USD.

PMID- 30101773
TI  - Decolorization of reactive dye Remazol Brilliant Blue R by zirconium oxychloride
      as a novel coagulant: optimization through response surface methodology.
AB  - The aim of the present study was to investigate the performance of a novel
      coagulant, i.e. ZrOCl2, for the removal of anthraquinone-based reactive dye from
      aqueous solution. An ideal experimental setup was designed based on central
      composite design using response surface methodology to determine the individual
      and interactive effects of different operational variables (i.e. pH, coagulant
      dose and dye concentration) on treatment performance in terms of dye and chemical
      oxygen demand (COD) removal efficiencies. Total 92.58% dye and 85.33% COD removal
      were experimentally attained at optimized conditions at low coagulant dose, i.e.
      156.67 mg/L for the dye concentration of 105.67 mg/L at pH 2. To validate the
      working pH of the metal coagulant, the static charge of ZrOCl2 was measured using
      Eh value. The performance of the coagulant was validated with experimental and
      predicted values in the selected data set, and R2 values for both responses were
      found to be 0.99 and 0.95 respectively, which shows the reliability of the
      experimental design. Further, the toxicity of the coagulant was assessed and no
      such toxicity was found even up to the concentration of 500 mg/L, proclaiming the
      disposal of sludge may not exhibit any threat to humans. Experimental results
      suggested that the ZrOCl2 could be used as an eco-friendly coagulant for dye
      wastewater treatment.

PMID- 30101774
TI  - Using image processing for determination of settled sludge volume.
AB  - Determination of the sludge volume index is key to describing the settling
      characteristics of sludge in the aeration process of wastewater treatment plants
      (WWTPs). The two core components of this calculation are the settled sludge
      volume (SSV) and suspended solids. While the measurement procedure for SSV is
      generally defined by national or international standards, in practice a wide
      variety of vessel sizes and shapes are used by operators to monitor WWTP
      performance. Furthermore, differences in how these tests are carried out can lead
      to poor data, inefficient WWTP operation and a lack of comparable metrics for
      WWTP operational monitoring. Thus, there is a requirement to improve operational
      performance of WWTPs to meet the increasingly stringent legislation regarding
      discharge limits. The aim of this study was to utilise a novel image-processing
      system (AutoSSV) to (i) determine its efficacy in describing SSV and (ii) measure
      and compare different methodologies for measurement of SSV. The AutoSSV system
      was tested using samples from various WWTPs and the results compared to those
      determined by standard manual measurement. Both standard and modified settlement
      tests were conducted on 30 mixed liquor samples, with modified settlement tests
      consistently resulting in lower SSV measurements. Results from the study showed a
      strong correlation between the SSV measurements provided by the AutoSSV system
      and results obtained from current manual measurement methods. The proposed
      technique would help to standardise the measurement in practice and increase the
      frequency of monitoring, particularly in small-scale rural WWTPs where there may
      not be permanent operators on site, and thus provide sufficient performance
      monitoring for efficient and effective operation.

PMID- 30101775
TI  - Selective adsorption of organic dyes by porous hydrophilic silica aerogels from
      aqueous system.
AB  - Hydrophilic silica aerogel (HSA) was obtained by sol-gel method and dried at
      ambient conditions and further studied for the removal of organic dyes in water.
      Silica aerogel was characterized by its morphology, porous structure, specific
      surface area and particle size distribution by scanning electron microscopy,
      Brunauer-Emmett-Teller and pore size distribution. The HSA after calcination had
      a specific surface area of 888.73 m2/g and an average particle size of 2.6341 nm.
      Moreover, adsorption properties of the HSA toward organic dyes - adsorption
      conditions, kinetics data, and equilibrium model - were investigated. The removal
      rate of cationic dyes (rhodamine B (RhB), methylene blue (MB) and crystal violet
      (CV)) by HSA was up to 90%, while the removal rate of anionic dye (acid orange 7)
      was not more than 30%. The maximum adsorptions were: RhB 191.217 mg/g, MB 51.1601
      mg/g and CV 24.85915 mg/g, respectively. Based on the adsorption mechanism of HSA
      for cationic/anionic dyes, the conclusion confirmed the prospect of HSA as
      effective adsorbent to treat cationic dyes wastewater.

PMID- 30101776
TI  - Coagulation performance of cucurbit[8]uril for the removal of azo dyes: effect of
      solution chemistry and coagulant dose.
AB  - Dye wastewater has attracted significant attention because of its wide pH range
      and high content of color. In this work, the coagulation performances of
      cucurbit[8]uril for the removal of color from acid red 1 (AR1), orange II (OII),
      and Congo red (CR) dye wastewaters were investigated. Experimental results showed
      that color removal rates of greater than 95% for AR1, OII and CR were achieved at
      pH 6.0, when the dosage of cucurbit[8]uril was 1.51, 3.01 and 0.38 mmol.L-1,
      respectively. Under identical conditions, the color removal efficiencies of AR1
      and CR were higher than OII, due to the larger molecular weights and more active
      hydroxyl and amino groups. Moreover, steady increases in AR1, OII and CR removal
      rates were recorded with increasing ionic strength. Such increases may be related
      to the reduction in thickness of the surface solvent membrane surrounding the dye
      colloids at high ionic strengths. Furthermore, Fourier transform infrared spectra
      demonstrated that no new bonds or functional groups were formed during
      coagulation, which indicates that the removal of AR1, OII and CR was primarily a
      physical process. The hydrogen bonds and inclusion complexes formed between
      cucurbit[8]uril and AR1, OII and CR contributed to the removal of color in
      coagulation predominantly.

PMID- 30101777
TI  - Photolysis of cyflufenamid in liquid media.
AB  - The photolysis of cyflufenamid (CFA) in different organic solvents and water
      under ultraviolet irradiation was investigated. The photolytic rate constant and
      photolytic half-life were measured for the different solutions. Factors
      influencing the photolysis of CFA were investigated, including initial
      concentration, types of solvent, pH, occurrence of catalyst (TiO2), and
      environmental substances (Fe3+, Fe2+, NO3-, NO2-). Photolysis of CFA followed
      first-order kinetics in various systems, and the photolytic rate of CFA decreased
      with increased initial concentration. Photolytic rates of CFA in different
      solvents were as follows: n-hexane > methanol > acetonitrile > ultrapure water >
      ethyl acetate. The pH had a significant effect on the photolysis of CFA, and the
      photolysis rate reached its peak at pH 9.0. NO2- and TiO2 had positive effects on
      the photolysis of CFA, while Fe2+ had an adverse effect. NO3- in aqueous solution
      had no effect on the photolysis of CFA. In addition, the rates of photolysis were
      accelerated at lower concentrations of Fe3+ (0.5-5 mmol L-1) and decreased at
      higher concentrations (10 mmol L-1). Moreover, a main photolytic product of CFA
      was confirmed to be N-cyclopropoxy-2,3-difluoro-6-(trifluoromethyl)benzamide, and
      cleavage of the amido bond was proposed to be the predicted photolysis pathway in
      n-hexane.

PMID- 30101778
TI  - A novel chemical sensor with multiple all-solid-state electrodes and its
      application in freshwater environmental monitoring.
AB  - Freshwater quality detection is important for pollution control. Three important
      components of water quality are pH, ammonia and dissolved H2S and there is an
      urgent need for a high-precision sensor for simultaneous and continuous
      measurement. In this study, all-solid-state electrodes of Eh, pH, NH4+ and S2-
      were manufactured and mounted to a wireless chemical sensor with multiple
      parameters. Calibration indicated that the pH electrode had a Nernst response
      with slope of 53.174 mV; the NH4+ electrode had a detection limit of 10-5 mol/L
      (Nernst response slope of 53.56 mV between 10-1 to 10-4 mol/L). Ag/Ag2S has a
      detection limit of 10-7 mol/L (Nernst response slope of 28.439 mV). The sensor
      was cylindrical and small with low power consumption and low storage demand to
      achieve continuous in-situ monitoring for long periods. The sensor was tested for
      10 days in streams at Trawsgoed Dairy farm in Aberystwyth, UK. At the intensively
      farmed Trawsgoed, the concentration of NH4+ in the stream rose sharply after the
      application of slurry to adjacent fields. Further, the stream was overhung with
      extensive vegetation and exhibited changes in pH, which correlated with
      photosynthetic activity. Measurements of S2- were stable throughout the week. Our
      data demonstrate the applicability of our multiple electrode sensor.

PMID- 30101779
TI  - Sinks and sources of anammox bacteria in a wastewater treatment plant - screening
      with qPCR.
AB  - The deammonification process, which includes nitritation and anammox bacteria, is
      an energy-efficient nitrogen removal process. Starting up an anammox process in a
      wastewater treatment plant (WWTP) is still widely believed to require external
      seeding of anammox bacteria. To demonstrate the principle of a non-seeded anammox
      start-up, anammox bacteria in potential sources must be quantified. In this
      study, seven digesters, their substrates and reject water were sampled and
      quantitative polymerase chain reaction (qPCR) was used to quantify both total and
      viable anammox bacteria. The results show that mesophilic digesters fed with
      nitrifying sludge (with high sludge ages) can be classified as a reliable source
      of anammox bacteria. Sludge hygienization and dewatering of digestate reduce the
      amount of anammox bacteria by one to two orders of magnitude and can be
      considered as a sink. The sampled reject waters contained on average >4.0 * 104
      copies mL-1 and the majority of these cells (>87%) were viable cells.
      Furthermore, plants with side-stream anammox treatment appear to have higher
      overall quantities of anammox bacteria than those without such treatment. The
      present study contributes to the development of sustainable strategies for both
      start-up of anammox reactors and the possibility of improving microbial
      management in WWTPs.

PMID- 30101780
TI  - A bioflocculant-supported dissolved air flotation system for the removal of
      suspended solids, lipids and protein matter from poultry slaughterhouse
      wastewater.
AB  - In this study, two previously identified isolates, i.e. Comamonas aquatica (BF-3)
      and Bacillus sp. BF-2, were determined to be suitable candidates to utilise in a
      bioflocculant-supported dissolved air flotation (Bio-DAF) system as a
      pretreatment system for poultry slaughterhouse wastewater (PSW). A 2% (v/v)
      (bioflocculant:PSW) strategy was used for the DAF to reduce total suspended
      solids (TSS), lipids and proteins in the PSW, by supplementing the bioflocculants
      produced and the co-culture (C. aquatica BF-3 and Bacillus sp. BF-2) directly
      into the DAF. The Bio-DAF was able to reduce 91% TSS, 79% proteins and 93% lipids
      when the DAF system was operating at steady state, in comparison with a chemical
      DAF operated using 2% (v/v) alum that was able to only reduce 84% TSS, 71%
      proteins and 92% lipids. It was concluded that the Bio-DAF system worked
      efficiently for the removal of suspended solids, lipids and proteins, achieving
      better results than when alum was used.

PMID- 30101782
TI  - Editorial: Algal technologies for wastewater treatment and resource recovery.

PMID- 30101781
TI  - On-site single-stage constructed wetland fed by raw wastewater: performances and
      resilience of the system.
AB  - On-site sanitation systems in Europe are evaluated through a CE marked procedure
      done on a platform test under a specific schedule of loads. Nevertheless, the
      test procedure conditions do not represent the real conditions of treatment
      systems in terms of wastewater characteristics and loads. On another angle, in
      France, systems implemented for capacities above 20 p.e. do not need the CE
      marked procedure but have to comply with performance requirements. French on-site
      treatment regulations lead to a paradoxical situation where constructed wetlands
      (CW) designed for 21 p.e. can be more compact than for 15 p.e. Here we focus on a
      single-stage vertical flow CW treating raw wastewater from a six-person house.
      Working with a (compact) community CW design, the objectives were to evaluate, in
      real-world conditions, the limits of the system and its ability to handle the
      high hydraulic and organic load variations found in on-site sanitation.
      Concentrations and fluxes showed high inter-day and intra-day variability,
      confirming the necessity for treatment systems to be robust enough for on-site
      sanitation. The compact CW appeared very efficient and stable for organic
      pollutants and nitrification (average removal rates of more than 98%, 99%, 94%
      and 97% for TSS, BOD5, COD and TKN, respectively). Denitrification has been
      optimized to reach 70% of TN removal, but seems unable to go higher due to a lack
      of carbon.

PMID- 30101783
TI  - Comparison of the treatment performance of a high rate algal pond and a
      facultative waste stabilisation pond operating in rural South Australia.
AB  - South Australian community wastewater management schemes (CWMS) treat wastewater
      using waste stabilisation ponds before disposal or reuse. This study compared the
      performance of a facultative pond, 6,300 m2, 27.5 d theoretical hydraulic
      retention time (THRT), with a high rate algal pond (HRAP) operated at depths of
      0.32, 0.43 and 0.55 m with THRT equivalent to 4.5, 6.4 and 9.1 d respectively.
      Both ponds received influents of identical quality, differing only in quantity,
      and were operated in similar climatic conditions. The depth of HRAP operation had
      only a minor influence on treatment performance. The study showed that the
      quality of the treated effluent from the HRAP was equivalent to that of the
      facultative pond, 5-day biochemical oxygen demand removal >89%, NH4-N removal
      59.09-74.45%. Significantly, Escherichia coli log10 reduction values by the HRAP,
      1.74-2.10, were equivalent to those of the facultative pond. Consequently, HRAPs
      could replace facultative ponds within CWMS while maintaining treated effluent
      quality. The benefit would be halving the surface area requirement from 4.2 m2
      capita-1 for the facultative pond to between 2.0 and 2.3 m2 capita-1, depth
      dependent, for an HRAP, with significant attendant reductions in the capital
      costs for construction.

PMID- 30101784
TI  - Energy recovery in high rate algal pond used for domestic wastewater treatment.
AB  - High rate algal pond (HRAP) was evaluated according to its energy potential and
      productivity by two rates, net energy ratio (NER) and specific biomass
      productivity. All energy inputs were calculated according to one HRAP with pre
      ultraviolet disinfection treating anaerobic domestic sewage. The outputs were
      calculated for two energetic pathways: lipid and biogas production for the raw
      biomass (RB) and biomass after lipid extraction. The non-polar lipid content in
      dry biomass was 7.6%, reaching a daily lipid productivity of 0.2 g/m2.day and the
      biogas production potential was 0.20 m3/kg solids. For the biomass after lipid
      extraction, the biogas production reached 2.6 m3/kg solids. NER values of 10-3
      for the RB were similar for lipids and biogas routes. The specific biomass
      productivity was 0.7 mg/kJ. For the residual biomass, after lipid extraction, NER
      value was 10-2 for the integrated route (lipids + biogas) and the specific
      biomass productivity of the extracted biomass was 0.4 mg/kJ. The best energetic
      pathway was to integrate both lipids and biogas route.

PMID- 30101785
TI  - Investigation and modelling of high rate algal ponds utilising secondary effluent
      at Western Water, Bacchus Marsh Recycled Water Plant.
AB  - There is growing interest in the ability of high rate algal ponds (HRAP) to treat
      wastewater. This method reduces the costs of algal production while treating the
      wastewater quicker and more efficiently than standard lagoon practices. Two
      parallel HRAPs were used in this study to treat secondary effluent. Nitrogen
      levels were significantly reduced with a mean reduction of 71% for ammonia and
      64% for total nitrogen. The use of the HRAPs significantly increased the algal
      biomass levels compared to the algal growth in the storage lagoons, with a mean
      increase of 274%. Beneficial use of algae can be used to reduce treatment costs;
      so being able to predict and optimise the amount of algal biomass produced in
      HRAPs is vital. However, most models are complicated and require specific,
      detailed information. In this study, a predictive microalgal growth model was
      developed for HRAP by adapting two previously established models: the Steele and
      Monod models. The model could predict algal growth based on temperatures and
      solar radiation and account for limiting ammonia concentrations in an elevated pH
      environment with natural variations in the algal community. This model used
      experimental data that would be readily available to any established HRAP study.

PMID- 30101786
TI  - Pond walls: inclined planes to improve pathogen removal in pond systems for
      wastewater treatment?
AB  - Attenuation of sunlight in wastewater treatment ponds reduces the depth of the
      water exposed to disinfecting irradiances. Shallow pond depth with paddlewheel
      rotation increases exposure of pathogens to sunlight in high rate algal ponds.
      Generation of thin films, using pond walls as inclined planes, may increase
      inactivation of pathogens by increasing sunlight exposure. The performance of a
      laboratory based model system incorporating an inclined plane (IP) was evaluated.
      F-RNA bacteriophage, in tap water or wastewater, was exposed to sunlight only on
      the IP with the bulk water incubated in the dark. MS2 inactivation was
      significantly higher when the IP was present (P < 0.05) with a 63% increase
      observed. Prolonged exposure increased MS2 die-off irrespective of IP presence.
      Versatility of the IP was also demonstrated with faster inactivation observed in
      both optically clear tap water and wastewaters. IPs of different surface areas
      produced similar inactivation rates when operated at similar hydraulic loading
      rates regardless of slope length.

PMID- 30101788
TI  - Tilapia rearing with high rate algal pond effluent: ammonia surface loading rates
      and stocking densities effects.
AB  - In two pilot-scale experiments, fingerlings and juvenile of tilapia were reared
      in high rate algal pond (HRAP) effluent. The combination of three different total
      ammonia nitrogen (TAN) surface loading rates (SLR1 = 0.6, SLR2 = 1.2; SLR3 = 2.4
      kg TAN.ha-1.d-1) and two fish stocking densities (D1 = 4 and D2 = 8 fish per
      tank) was evaluated during two 12-week experiments. Fingerlings total weight gain
      varied from 4.9 to 18.9 g, with the highest value (equivalent to 0.225 g.d-1)
      being recorded in SLR2-D1 treatment; however, high mortality (up to 67%) was
      recorded, probably due to sensitivity to ammonia and wide daily temperature
      variations. At lower water temperatures, juvenile tilapia showed no mortality,
      but very low weight gain. The fish rearing tanks worked as wastewater polishing
      units, adding the following approximate average removal figures on top of those
      achieved at the HRAP: 63% of total Kjeldahl nitrogen; 54% of ammonia nitrogen;
      42% of total phosphorus; 37% of chemical oxygen demand; 1.1 log units of
      Escherichia coli.

PMID- 30101787
TI  - Exploring the influence of meteorological conditions on the performance of a
      waste stabilization pond at high altitude with structural equation modeling.
AB  - Algal photosynthesis plays a key role in the removal mechanisms of waste
      stabilization ponds (WSPs), which is indicated in the variations of three
      parameters, dissolved oxygen, pH, and chlorophyll a. These variations can be
      considerably affected by extreme climatic conditions at high altitude. To
      investigate these effects, three sampling campaigns were conducted in a high
      altitude WSP in Cuenca (Ecuador). From the collected data, the first application
      of structure equation modeling (SEM) on a pond system was fitted to analyze the
      influence of high-altitude characteristics on pond performance, especially on the
      three indicators. Noticeably, air temperature appeared as the highest influencing
      factors as low temperature at high altitude can greatly decrease the growth rate
      of microorganisms. Strong wind and large diurnal variations of temperature, 7-20 
      degrees C, enhanced flow efficiency by improving mixing inside the ponds. Intense
      solar radiation brought both advantages and disadvantages as it boosted oxygen
      level during the day but promoted algal overgrowth causing oxygen depletion
      during the night. From these findings, the authors proposed insightful
      recommendations for future design, monitoring, and operation of high-altitude
      WSPs. Moreover, we also recommended SEM to pond engineers as an effective tool
      for better simulation of such complex systems like WSPs.

PMID- 30101789
TI  - Microalgae cultivation in agro-industrial effluents for biodiesel application:
      effects of the availability of nutrients.
AB  - The present study evaluated the cultivation of microalgae in a photobioreactor
      using effluents from the meat-processing industry, which had been previously
      treated at the primary and secondary levels. Scenedesmus sp. was the dominant
      genus in the phytoplankton community in both of the evaluated effluents. The
      different nutritional conditions affected the production of biomass, which
      reached 1,160 mg/L of volatile suspended solids (VSS) and 371 mg/L of VSS with
      cultivation in the primary (PE) and secondary effluents (SE), respectively. In
      both effluents, great removal efficiencies close to quantification limits were
      observed for ammoniacal nitrogen and soluble phosphorus. Regarding the
      accumulation of lipids, there were no considerable differences between the
      effluents. The highest lipid productivity that was observed in the PE, which
      reached 3.7 g/m2.d, was attributed to its larger production of biomass as a
      consequence of its better nutritional condition in relation to the SE.

PMID- 30101790
TI  - Microalgae cultivation for wastewater treatment and biogas production at Moscow
      wastewater treatment plant.
AB  - The process of cultivation of microalgae on purified and clarified wastewater of
      Kuryanovo wastewater treatment plants (KWWTP) was studied. The studies were
      conducted on monoculture (Scenedesmus quadricauda and Chlorella sorokiniana) and
      on polyculture, the composition of which was formed from microalgae present in
      the wastewater. The authors created and investigated the columnar photobioreactor
      (PBR), which acted as a pilot project on the purified and clarified water of
      KWWTP and allowed the removal of total nitrogen and phosphorus phosphates with an
      efficiency of up to 90%. The formation of a stable biocenosis from 22 species of
      algae (with 3-4 dominant species) and 31 species of zooplankton organisms
      belonging to six systematic subdivisions was recorded. The optimal retention time
      of the microalgae polyculture for the most effective wastewater treatment has
      been determined. The conducted studies have shown that the depth of decomposition
      of ashless matter and the ultimate biogas potential of untreated microalgae
      biomass is 15% lower than the corresponding values obtained with digestion of
      activated sludge, which necessitates studies in the field of pretreatment of
      algal biomass. The paper shows: connections between chlorophyll-a content, algal
      biomass and fluorescence index F0 and between biomass increment and Fv/Fm value.

PMID- 30101791
TI  - Improved methane yield from wastewater grown algal biomass.
AB  - Methane production from the algal biomass cultivated in a laboratory scale
      continuous photobioreactor (PBR) using sewage was evaluated in the present work.
      During the preliminary experiments, algal biomass reached up to 1.69 +/- 0.35 g L
      1 in 12 days' growth period. Besides, 65 to 100% removal in concentrations of
      total dissolved phosphorus (TDP), nitrate nitrogen (NO3-N), total ammoniacal
      nitrogen (TAN) and soluble chemical oxygen demand (sCOD) was also recorded. The
      sCOD removal in the reactor was 100%, whereas removal of TDP, NO3-N and TAN were
      up to 75, 40 and 92%, respectively. Upon anaerobic digestion, the fresh algal
      biomass showed methane yield of 180 mL g-1 VSfed. Further, algal biomass was
      stored under natural conditions in open containers (aerobic conditions) in
      darkness at room temperature (27-30  degrees C) for 72 h. Interestingly, >48% COD
      solubilization from algal biomass was observed during storage. Pretreatment
      through natural storage was further confirmed with qualitative observations
      including scanning electron and fluorescence microscopic analysis. Moreover,
      higher methane yield (284.38 mL g-1 VSfed) was observed from the samples stored
      for 60 h. Thus, natural storage for a designated period may be recommended as a
      prerequisite stage in the process of methane production from wastewater-grown
      algal biomass.

PMID- 30101792
TI  - Enhanced biogas production potential of microalgae and swine wastewater using co
      digestion and alkaline pretreatment.
AB  - Biogas yield obtained from anaerobic digestion of swine wastewater (SWW) needs to
      be increased to produce electrical energy. To enhance biogas and prevent
      pollution, use of mixed culture microalgae grown in wastewater (MWW) with SWW has
      attracted a lot of interest. This research was focused on the possibility of
      utilizing MWW. Six experiments using raw SWW and MWW, and their co-digestion were
      conducted on a laboratory scale in one-litre reactors with the ratio of inoculum
      and substrate of 70:30 under without and with alkaline pretreatment (using 3%
      NaOH for pH adjustment every 15 min at pH 11 for 3 h). The results showed that co
      digestion had the major effect on increasing biogas and methane yields (0.735 and
      0.326 m3/kg of volatile solids (VS) removed), and the highest chemical oxygen
      demand and VS removal (60.29% and 63.17%). For pretreatment, the effect of
      ammonia inhibition at a high pH of 11 had more influence on biodegradation than
      the effect of destruction of MWW's cell walls, resulting in a low biogas
      production of pretreated MWW and pretreated co-digestion. These findings affirm
      the potential of co-digestion, and the possibility of using both single and co
      substrate MWW. Pretreatment could be improved at a lower alkaline pH condition. A
      pilot scale of co-digestion should be performed.

PMID- 30101793
TI  - Biogas from mono- and co-digestion of microalgal biomass grown on piggery
      wastewater.
AB  - Biogas production has been suggested as a valid valorization solution for
      microalgal/bacteria biomass (MAB) grown on wastewater. This research is aimed at
      assessing the feasibility to use MAB grown in an outdoor raceway fed on piggery
      wastewater for biogas production. Batch and continuous anaerobic tests were
      conducted on the sole MAB and on a blend of MAB and carbonaceous substrates
      (deproteinated cheese whey and cellulose) to improve the carbon/nitrogen ratio.
      Results of batch biochemical methane potential tests confirmed that the sole
      microalgal/bacteria biomass was poorly degradable (119 NmLCH4.gCOD-1), while
      blending it with deproteinated cheese whey or cellulose (80% of carbonaceous
      material and 20% of MAB, as chemical oxygen demand (COD)) had no synergistic
      effects on the methane yield, although slight improvements in the degradation
      kinetics were observed. Continuous anaerobic degradation tests (at an organic
      loading rate of 1.5 gCOD.L-1.d-1, 35  degrees C and 30 days of hydraulic
      retention time) increased the overall methane yield from 81 NmLCH4.gCOD-1 (sole
      MAB) to 216 NmLCH4.gCOD-1 (MAB and deproteinated cheese whey) and 122 NmLCH4.gCOD
      1 (MAB and cheese whey). However, data confirm that no evident synergistic
      effects were obtained.

PMID- 30101794
TI  - Start-up of a microalgae-based treatment system within the biorefinery concept:
      from wastewater to bioproducts.
AB  - Within the European project INCOVER, an experimental microalgae-based treatment
      system has been built for wastewater reuse and added-value products generation.
      This article describes this new experimental plant and the start-up stage,
      starting from the new design of three semi-closed horizontal photobioreactors
      with low energy requirements for microalgae cultivation (30 m3 total), using
      agricultural runoff and urban wastewater as feedstock. The inflow nutrients
      concentration is adjusted to select cyanobacteria, microalgae able to accumulate
      polyhydroxybutyrates, which can be used for bioplastics production. Part of the
      harvested biomass is used as substrate for anaerobic co-digestion (AcoD) with
      secondary sludge to obtain biogas. This biogas is then cleaned in an absorption
      column to reach methane concentration up to 99%. The digestate from the AcoD is
      further processed in sludge wetlands for stabilization and biofertilizer
      production. On the other hand, treated water undergoes ultrafiltration and
      disinfection through a solar-driven process, then it is pumped through absorption
      materials to recover nutrients, and eventually applied in an agricultural field
      to grow energy crops by means of a smart irrigation system. This plant presents a
      sustainable approach for wastewater management, which can be seen as a resource
      recovery process more than a waste treatment.

PMID- 30101795
TI  - Co-digestion of microalga-bacteria biomass with papaya waste for methane
      production.
AB  - The anaerobic co-digestion of microalga-bacteria biomass and papaya waste
      (MAB/PW) was evaluated under semi-continuous conditions. Microalgae-bacteria
      biomass was obtained from a high rate algal pond fed with municipal wastewater
      and artificially illuminated. The co-digestion of MAB/PW was evaluated using a
      1:1 (w/w) ratio and an organic loading rate of 1.1 +/- 0.1 g COD/L/d. Enzymatic
      activity assays of papain were performed in the feeding to determine the activity
      of this enzyme in the substrate mixture. A methane yield of 0.55 L CH4/gVS and
      68% of total volatile solid removal were observed. The volumetric productivity
      was 0.30 +/- 0.03 L CH4/L/d with a methane content of 71%. It was observed that
      papaya waste was a suitable co-substrate because it maintained a low ammonium
      concentration, decreasing the risk of inhibition due to ammonia and then
      increasing the methane yield of the microalgae-bacteria biomass compared to the
      biomass alone. The pretreatment effect by the addition of papaya waste on the
      microalgae-bacteria biomass was supported by the papain activity remaining in the
      substrate.

PMID- 30101796
TI  - Valorization of waste micro-algal biomass - collected from coke oven effluent
      treatment plant and evaluation of sorption potential for fluoride removal.
AB  - Fluoride contamination in groundwater is now becoming a global concern. In the
      present study, removal of fluoride using dry biomass (DBM) of a micro-algal
      consortium of Chlorococcum infusionum and Leptolyngbya foveolaurum, collected
      from a coke-oven effluent treatment plant, Durgapur, India, has been
      investigated. The large volume of algal bloom in the industrial effluent has
      created serious disposal issues and caused severe environmental concerns. A
      biosorption technique has been carried out to valorize the waste algae biomass
      into a potential adsorbent. Response Surface Methodology (RSM) is used to model
      and optimize fluoride removal. Maximum fluoride removal (72%) is obtained at pH
      4, 5 mg/L initial fluoride concentration, 0.5 g/L adsorbent dose (AD), and 25 
      degrees C temperature during one-factor-at-a-time (OFAT) analysis. The optimum
      condition of removal as specified by RSM is - initial concentration of fluoride:
      30 mg/L, pH: 4.5, AD: 3.5 g/L and temperature: 30  degrees C. FESEM-EDX, FTIR and
      BET isotherm studies are done to characterize raw and fluoride treated biomass.
      Lagergren first order kinetic model and Freundlich isotherm model, are found to
      analyze best kinetic and equilibrium data, respectively. Adsorption capacity of
      DBM has been found to be 34.36 mg/g. The kinetics of fluoride removal have been
      well described by COMSOL Multiphysics.

PMID- 30101797
TI  - Removal of copper from an electroplating industrial effluent using the native and
      modified spirogyra.
AB  - In the present study, biosorption behavior of a green filamentous alga, spirogyra
      in its native and modified states was investigated for copper removal from an
      electroplating industrial effluent. For this, the effluent containing 194 mg.L-1
      Cu2+ in sulfate medium was contacted with both forms of spirogyra, under the
      parametric variations of effluent pH, adsorbent dosage, contact time, and
      sorption temperature. The study revealed spirogyra as a prominent candidate for
      removing contaminant metal cation; however, at the same condition, biosorption
      capacity of modified biomass in gel form was higher than the native spirogyra. At
      the optimized condition with 6 g sorbent dosage treated to 100 mL effluent for 30
      min at pH 6.0 and temperature 20  degrees C, the maximum 82.8% and 96.4% copper
      could be adsorbed by the native and modified spirogyra, respectively. The batch
      sorption data using native biomass followed pseudo-first-order kinetic;
      exhibiting the multilayer sorption mechanism via surface diffusion could be
      defined by the Freundlich model. In contrast, the sulfuric acid treated modified
      spirogyra followed pseudo-second-order kinetics and intra particle diffusion as
      the rate-limiting step.

PMID- 30101798
TI  - Effective adsorption of nickel (II) with Ulva lactuca dried biomass: isotherms,
      kinetics and mechanisms.
AB  - This study aimed to evaluate the Ni2+ ions adsorption capability of Ulva lactuca.
      The isotherms, kinetics and mechanisms for the adsorption of Ni2+ from aqueous
      solution by Ulva lactuca were also investigated. Influencing factors including
      initial pH, initial Ni2+ concentration, biomass, contact time were examined. The
      results indicate that the maximum Ni2+ adsorption capacity of 38.28 mg/g was
      obtained at pH 5, initial Ni2+ concentration 250 mg/L, biomass dosage 0.5 g/L and
      contact time 30 min. The adsorption can be well fitted with Langmuir isotherm,
      and the kinetics were well described by the pseudo-second-order model. The
      parameters of thermodynamics verified that Ni2+ adsorption on Ulva lactuca was a
      spontaneous and endothermic process. Analyses of FT-IR, SEM-EDS and XPS indicate
      that carboxyl and hydroxyl groups on the surface of biomass are involved in Ni2+
      adsorption. The dried biomass of Ulva lactuca can be a cost-effective and eco
      friendly adsorbent for the removal of Ni2+ from wastewater.

PMID- 30101799
TI  - Microalgal luxury uptake of phosphorus in waste stabilization ponds - frequency
      of occurrence and high performing genera.
AB  - Microalgae commonly found in waste stabilization ponds (WSPs) are able to
      accumulate elevated phosphorus levels within their cells in a process known as
      luxury uptake. However, there are few studies focused on luxury uptake in full
      scale WSPs. In order to comprehensively quantify the occurrence of this
      phenomenon, eight different WSP sites comprising seven primary facultative, six
      maturation and two high rate algal ponds (HRAPs) spread over several climatic
      regions were monitored over four seasons. Of the 15 ponds studied, 13 of these
      exhibited elevated levels of biomass phosphorus content at some point; however,
      the occurrence in HRAPs was limited. More than half of the samples tested had
      elevated phosphorus contents and this occurred in all climatic zones surveyed.
      The phosphorus content of the biomass was significantly correlated to decreasing
      rainfall and increasing total dissolved phosphorus. Microscopic analysis revealed
      that nearly all the 17 microalgal and five cyanobacterial genera identified
      performed luxury uptake, but at varying frequencies. This is the first time that
      the genera of algae responsible for luxury uptake in full scale WSPs has been
      studied. Chlamydomonas/Cryptomonas, Micractinium/Microcystis and Scenedesmus were
      the only microalgal genera found to both commonly occur in WSPs and consistently
      perform luxury uptake.

PMID- 30101800
TI  - Enhanced nitrogen removal and energy saving in a microalgal-bacterial consortium
      treating real municipal wastewater.
AB  - The optimization of total nitrogen removal from municipal wastewater was
      investigated in a laboratory-scale photo-sequencing batch reactor (PSBR) operated
      with a mixed microalgal-bacterial consortium spontaneously acclimatized to real
      wastewater. No external aeration was provided in the PSBR to reduce energy
      consumption: oxygen was only supplied by the microalgal photosynthesis. The
      enhancement of total nitrogen removal was achieved through: (1) feeding of
      wastewater in the dark phase to provide readily biodegradable COD when oxygen was
      not produced, promoting denitrification; (2) intermittent use of the mixer to
      favor simultaneous nitrification-denitrification inside the dense flocs and to
      achieve 41% energy saving with respect to continuous mixing. Efficient COD
      removal (86 +/- 2%) was observed, obtaining average effluent concentrations of 37
      mg/L and 22 mg/L of total COD and soluble COD, respectively. TKN removal was 97
      +/- 3%, with an average effluent concentration of 0.5 +/- 0.7 mg NH4+-N/L.
      Assimilation of nitrogen by heterotrophic bacteria accounted only for 20% of TKN
      removal, whilst the major part of TKN was nitrified. In particular, the
      nitrification rate was 1.9 mgN L-1 h-1 (specific rate 2.4 mgN gTSS-1 h-1),
      measured with dissolved oxygen near zero, when the oxygen demand was higher than
      the oxygen produced by photosynthesis. Total nitrogen of 6.3 +/- 4.4 mgN/L was
      measured in the effluent after PSBR optimization.

PMID- 30101801
TI  - Photosynthetic oxygenation for urine nitrification.
AB  - Human urine accounts for only a fraction of the sewage volume, but it contains
      the majority of valuable nutrient load in wastewater. In this study, synthetic
      urine was nitrified in a closed photo-bioreactor through photosynthetic
      oxygenation by means of a consortium of microalgae and nitrifying bacteria. In
      situ production of oxygen by photosynthetic organisms has the potential to reduce
      the energy costs linked to conventional aeration. This energy-efficient strategy
      results in stable urine for further nutrient recovery, while part of the
      nutrients are biologically recovered in the form of valuable biomass. In this
      study, urine was nitrified for the first time without conventional aeration at a
      maximum photosynthetic oxygenation rate of 160 mg O2 gVSS-1 d-1 (VSS: volatile
      suspended solids). A maximum volumetric nitrification rate of 67 mg N L-1 d-1 was
      achieved on 12% diluted synthetic urine. Chemical oxygen demand (COD) removal
      efficiencies were situated between 44% and 83% at a removal rate of 24 mg COD
      gVSS-1 d-1. After 180 days, microscopic observations revealed that Scenedesmus
      sp. was the dominant microalga. Overall, photosynthetic oxygenation for urine
      nitrification is promising as a highly electricity efficient approach for further
      nutrient recovery.

PMID- 30101802
TI  - Outdoor flat-panel membrane photobioreactor to treat the effluent of an anaerobic
      membrane bioreactor. Influence of operating, design, and environmental
      conditions.
AB  - As microalgae have the ability to simultaneously remove nutrients from wastewater
      streams while producing valuable biomass, microalgae-based wastewater treatment
      is a win-win strategy. Although recent advances have been made in this field in
      lab conditions, the transition to outdoor conditions on an industrial scale must
      be further investigated. In this work an outdoor pilot-scale membrane
      photobioreactor plant was operated for tertiary sewage treatment. The effects of
      different parameters on microalgae performance were studied including:
      temperature, light irradiance (solar and artificial irradiance), hydraulic
      retention time (HRT), biomass retention time (BRT), air sparging system and
      influent nutrient concentration. In addition the competition between microalgae
      and ammonium oxidising bacteria for ammonium was also evaluated. Maximum nitrogen
      and phosphorus removal rates of 12.5 +/- 4.2 mgN.L-1.d-1 and 1.5 +/- 0.4 mgP.L
      1.d-1, respectively, were achieved at a BRT of 4.5 days and HRT of 2.5 days,
      while a maximum biomass productivity of 78 +/- 13 mgVSS.L-1.d-1 (VSS: volatile
      suspended solids) was reached. While the results obtained so far are promising,
      they need to be improved to make the transition to industrial scale operations
      feasible.

PMID- 30101803
TI  - Activity assessment of microalgal-bacterial consortia based on respirometric
      tests.
AB  - Respirometric techniques are useful tools to evaluate bacterial activities in
      activated sludge processes due to their fast execution and the possibility to
      obtain several kinetic parameters from a single test. Using such techniques in
      microalgae-bacteria consortia treating wastewater could allow a better
      understanding of mutual interactions between the microbial populations as a
      function of environmental parameters. This work aims at developing and testing a
      novel experimental respirometric protocol to determine oxygen uptake rates and
      oxygen production rates by a microalgae-bacteria consortium. The defined protocol
      is characterized by alternating light/dark regimes and by dosing
      substrates/inhibitors to selectively activate/inactivate microalgal and bacterial
      metabolisms. The protocol was then applied on microalgal and bacterial consortia,
      which were grown on the liquid fraction of black water from biogas plants fed on
      agricultural and municipal waste sludge. Results elucidate the presence and
      activity of microalgae and nitrifying bacteria in the tested systems, suggesting
      that the respirometric tests could be included into monitoring procedures of
      photobioreactors/algal ponds.

PMID- 30101804
TI  - Exploiting symbiotic interactions between Chlorella protothecoides and
      Brevundimonas diminuta for an efficient single-step urban wastewater treatment.
AB  - The application of microalgal bacteria consortia to the treatment of wastewater
      is receiving increasing attention, meeting the demand for new green and efficient
      technologies for water remediation. The specificity of the consortium, however,
      may strongly affect the performance of the treatment. In fact, even though a
      general exploitation of the O2/CO2 exchange between microalgae and bacteria is
      effective, some specific interactions may increase the pollutant removal. With
      this aim, the co-cultivation of Chlorella protothecoides and Brevundimonas
      diminuta was tested, with particular attention to the removal capability of
      nitrogen, phosphorus and chemical oxygen demand (COD) from wastewater. Batch
      experiments were carried out both for the consortium and, separately, for the
      bacteria and microalgae alone, in order to compare their performances. B.
      diminuta showed a remarkable capability for removing organic substances and
      transforming organic nitrogen to ammonium. C. protothecoides efficiently removed
      nitrogen and phosphorus. As the specific growth rates of the two organisms are
      different, the co-cultivation was also carried out also in a continuous system,
      and the effect of hydraulic retention time (HRT) on the steady-state biomass
      concentration and nutrient removal efficiency was verified. Residence time was
      found as the main operating variable for obtaining a significant reduction of
      pollutants from wastewater.

PMID- 30101805
TI  - Treatment of food waste digestate using microalgae-based systems with low
      intensity light-emitting diodes.
AB  - Anaerobic digestion of food wastes coupled with digestate post-treatment using
      microalgae-based systems could recover large amounts of energy and nutrients
      worldwide. However, the development of full-scale implementations requires
      overcoming microalgae inhibition by high ammonia concentrations and low light
      transmittances affecting photosynthesis. This study evaluated the potential of
      microalgae-based reactors supplied with red light-emitting diodes (LEDs) at low
      intensity (660 nm and 15 umol.m-2.s-1) to treat food waste digestate. LED
      reactors were compared with control reactors exposed to solar radiation. From a
      range of species in the inoculum, Chlorella vulgaris showed high adaptation to
      both lighting regimes and digestate environmental conditions, characterized by a
      C:N:P ratio of 74:74:1. Removal efficiencies for control and LED reactors were
      84.0% and 95.8% for soluble chemical oxygen demand (COD) and 89.4% and 53.0% for
      ammonia, respectively. Approximately 50% of ammonia in control reactor and 15% in
      LED reactor was lost from the systems, whereas 17% and 36% of ammonia was
      transformed to organic nitrogen in control and LED reactors, respectively. Low
      intensity LEDs maintained microalgae growth in levels similar to solar radiation
      and supported efficient digestate treatment, showing a potential for further
      application in optimization of full scale reactors at a relatively low energy
      cost.

PMID- 30101806
TI  - Synthesis, characterization and application of green seaweed mediated silver
      nanoparticles (AgNPs) as antibacterial agents for water disinfection.
AB  - A simple and eco-friendly method for the synthesis of hybrid bead silver
      nanoparticles (AgNPs) employing the aqueous extract derived from natural and
      renewable source namely tropical benthic green seaweed Ulva flexuosa was
      developed. This route involves the reduction of Ag+ ions anchored onto macro
      porous methacrylic acid copolymer beads to AgNPs for employing them as
      antibacterial agents for in vitro water disinfection. The seaweed extract itself
      acts as a reducing and stabilizing agent and requires no additional surfactant or
      capping agent for forming the AgNPs. The nanoparticles were analyzed using high
      resolution transmission electron microscopy, UV-Vis spectroscopy, Fourier
      transform infrared spectroscopy, scanning electron microscopy, energy dispersive
      X-ray analysis and inductively coupled plasma optical emission spectroscopy. The
      study elucidates that such biologically synthesized AgNPs exhibit potential
      antibacterial activity against two Gram positive (Bacillus subtilis,
      Staphylococcus aureus) and two Gram-negative (Escherichia coli, Pseudomonas
      aeruginosa) bacterial strains tested. The bacterial count in treated water was
      reduced to zero for all the strains. Atomic force microscopy was performed to
      confirm the pre- and post-state of the bacteria with reference to their treatment
      with AgNPs. Attributes like facile environment-friendly procedure, stability and
      high antibacterial potency propel the consideration of these AgNPs as promising
      antibacterial entities.

PMID- 30101807
TI  - Comment on: "Derivation of thyroid lymphoepithelial cysts from follicular cells".

PMID- 30101808
TI  - Outcomes after Traumatic Brain Injury with Concomitant Severe Extracranial
      Injuries.
AB  - Traumatic brain injury (TBI) is a leading cause of death and disability in trauma
      patients. Patients with TBI frequently sustain concomitant injuries in
      extracranial regions. The effect of severe extracranial injury (SEI) on the
      outcome of TBI is controversial. For 8 years, we retrospectively enrolled 485
      patients with the blunt head injury with head abbreviated injury scale (AIS) ? 3.
      SEI was defined as AIS ? 3 injuries in the face, chest, abdomen, and
      pelvis/extremities. Vital signs and coagulation parameter values were also
      extracted from the database. Total patients were dichotomized into isolated TBI
      (n = 343) and TBI associated with SEI (n = 142). The differences in severity and
      outcome between these two groups were analyzed. To assess the relation between
      outcome and any variables showing significant differences in univariate analysis,
      we included the parameters in univariable and multivariable logistic regression
      analyses. Mortality was 17.8% in the isolated TBI group and 21.8% in TBI with SEI
      group (P = 0.38), but the Glasgow Outcome Scale (GOS) in the TBI with SEI group
      was unfavorable compared to the isolated TBI group (P = 0.002). Patients with SBP
      ? 90 mmHg were frequent in the TBI with SEI group. Adjusting for age, GCS, and
      length of hospital stay, SEI was a strong prognostic factor for mortality with
      adjusted ORs of 2.30. Hypotension and coagulopathy caused by SEI are considerable
      factors underlying the secondary insults to TBI. It is important to manage not
      only the brain but the whole body in the treatment of TBI patients with SEI.

PMID- 30101809
TI  - Left Atrial Appendage Thrombus Prior to Atrial Fibrillation Ablation in the Era
      of Direct Oral Anticoagulants.
AB  - BACKGROUND: In atrial fibrillation (AF) patients, the effect of direct oral
      anticoagulant (DOACs) therapy on the incidence of left atrial appendage thrombus
      (LAT) remains poorly investigated. This study examined the prevalence and risk
      factors of LAT in AF patients on DOACs undergoing catheter ablation, and sought
      an anticoagulation strategy for LAT. Methods and Results: In 407 AF patients on
      DOACs, transesophageal echocardiography (TEE) was performed 1 day before
      ablation. If patients had LAT, initial DOACs were switched to dabigatran (300 mg)
      or warfarin based on their renal function; TEE was repeated after treatment for
      >=4 weeks. LAT was detected in 18 patients (4.4%). The prevalence of persistent
      AF and low-dose treatment/inappropriate dose reduction of DOACs, CHADS2/CHA2DS2
      VASc scores, serum N-terminal pro-brain natriuretic peptide levels, and LA
      dimension/LA volume index significantly increased in patients with LAT vs. those
      without LAT. AF rhythm on TEE and spontaneous echo contrast also increased in
      patients with LAT; LA appendage flow velocity decreased. In the multivariate
      analysis, persistent AF and inappropriately reduced DOAC dose were risk factors
      for LAT. On repeat TEE, LAT had disappeared in 13 of 16 patients treated with
      dabigatran and in 2 of 2 patients treated with warfarin. CONCLUSIONS: DOACs still
      carry a finite risk of LAT in AF patients. Inappropriately reduced DOAC dose
      should be avoided to minimize the thromboembolic risk. Regular-dose dabigatran
      may have therapeutic efficacy against LAT.

PMID- 30101810
TI  - Early Prediction of Cardiotoxicity From Cancer Chemotherapy - Can Baseline Strain
      Identify High-Risk Patients?

PMID- 30101811
TI  - Bicuspid Aortic Valve-Associated Aortic Dilatation - What Is the Mechanism of
      Bicuspid Aortopathy?

PMID- 30101813
TI  - [Chinese Journal of Nuclear Medicine and Molecular Imaging Volume 38, Number 7,
      July 25, 2018].

PMID- 30101812
TI  - Guidelines for Heart Disease Screening in Schools (JCS 2016/JSPCCS 2016) - Digest
      Version.

PMID- 30101814
TI  - Effects of Omitting Non-confounding Predictors From General Relative-Risk Models
      for Binary Outcomes.
AB  - BACKGROUND: The effects, in terms of bias and precision, of omitting non
      confounding predictive covariates from generalized linear models have been well
      studied, and it is known that such omission results in attenuation bias but
      increased precision with logistic regression. However, many epidemiologic risk
      analyses utilize alternative models that are not based on a linear predictor, and
      the effect of omitting non-confounding predictive covariates from such models has
      not been characterized. METHODS: We employed simulation to study the effects on
      risk estimation of omitting non-confounding predictive covariates from an excess
      relative risk (ERR) model and a general additive-multiplicative relative-risk
      mixture model for binary outcome data in a case-control setting. We also compared
      the results to the effects with ordinary logistic regression. RESULTS: For these
      commonly employed alternative relative-risk models, the bias was similar to that
      with logistic regression when the risk was small. More generally, the bias and
      standard error of the risk-parameter estimates demonstrated patterns that are
      similar to those with logistic regression, but with greater magnitude depending
      on the true value of the risk. The magnitude of bias and standard error had
      little relation to study size or underlying disease prevalence. CONCLUSIONS:
      Prior conclusions regarding omitted covariates in logistic regression models can
      be qualitatively applied to the ERR and the general additive-multiplicative
      relative-risk mixture model without substantial change. Quantitatively, however,
      these alternative models may have slightly greater omitted-covariate bias,
      depending on the magnitude of the true risk being estimated.

PMID- 30101815
TI  - Induced Abortion, Birth Control Methods, and Breast Cancer Risk: A Case-Control
      Study in China.
AB  - BACKGROUND: The association between induced abortion and birth control methods
      (including oral contraceptives and intrauterine devices) and breast cancer may
      vary among countries, due to the different usage and frequency of birth control
      methods and induced abortion among countries. A better understanding of this
      association may help in determining safer birth control methods for Chinese
      women. METHODS: A case-control study was conducted with a total of 794 cases and
      805 controls. Standardized questionnaires were used to collect information on
      demographic characteristics, exposure to induced abortion, birth control methods,
      and other risk factors for breast cancer. Multivariate logistic regression was
      conducted to explore the association between birth control methods and breast
      cancer. RESULTS: Multivariate logistic regression analyses showed that having a
      history of medical abortions, >=3 surgical abortions, or both medical and
      surgical abortions was associated with an increased risk of breast cancer in post
      menopausal women (odds ratio [OR] 2.48; 95% confidence interval [CI], 1.14-5.40).
      Pre-menopausal women who had used intra-uterine devices (IUDs) for more than 20
      years tended to have a lower breast cancer risk than other age-matched pre
      menopausal women (OR 0.41; 95% CI, 0.25-0.68). Both pre-menopausal and post
      menopausal women who had <20 years exposure to IUDs and those who had used two or
      more birth control methods (with the exception of women who used IUDs for more
      than 20 years) tended to have much higher breast cancer risk. CONCLUSION: The
      relationship between induced abortion and birth control methods and breast cancer
      was complex, though being exposed to induced abortion and two or more birth
      control methods in one's lifetime appeared to be risk factors for breast cancer
      in Chinese women.

PMID- 30101816
TI  - Regional expression of tyrosinase in central catecholaminergic systems of colored
      mice.
AB  - A relationship between coat color and behavioral characteristics has been
      reported for numerous species. We previously indicated that particular behavioral
      traits contributing to the genotype at the agouti locus manifest only when
      possessing a wild-type allele at the albino (i.e., tyrosinase: Tyr) locus. The
      present study was performed to investigate tyrosinase expression with marked
      activity in central nervous systems. The whole brain of male B10 and B10-c mice,
      a B10 congenic strain of the albino locus from BALB/c at 8 to 9 weeks of age, was
      removed and we obtained several regions of brain, especially catecholaminergic.
      Comparatively large amounts of Tyr mRNA and its translation products of
      approximately 68 kDa were found in the regions obtained, and definitely possessed
      the enzyme activity for the oxidation of L-tyrosine. The present results indicate
      the possibility that the amount of catecholamines produced in albino mice is
      higher than that of colored mice due to the deficit in tyrosinase heritably.

PMID- 30101817
TI  - Akt1-Mediated Muscle Growth Promotes Blood Flow Recovery After Hindlimb Ischemia
      by Enhancing Heme Oxygenase-1 in Neighboring Cells.
AB  - BACKGROUND: Resistance exercise has beneficial effects for patients with
      peripheral arterial diseases. The hypothesis that muscle growth promotes
      angiogenesis by interacting with neighboring cells in ischemic lesions was
      assessed. Methods and Results: Skeletal muscle-specific inducible Akt1 transgenic
      (Akt1-TG) mice that induce growth of functional skeletal muscles as a model of
      resistance training were used. Proteomics analysis identified significant
      upregulation of heme oxigenase-1 (HO-1) in muscle tissue in Akt1-TG mice compared
      with control mice. Blood flow recovery after hindlimb ischemia was significantly
      increased in Akt1-TG mice compared with control mice. Enhanced blood flow and
      capillary density in Akt1-TG mice were completely abolished by the HO-1
      inhibitor, Tin-mesoporphyrin. Immunohistochemistry showed that HO-1 expression
      was not increased in muscle cells, but it was increased in macrophages and
      endothelial cells. Consistent with these findings, blood flow recovery after
      hindlimb ischemia was similar between control mice and skeletal muscle-specific
      HO-1-knockout mice. Adenoviral-mediated overexpression of Akt1 did not increase
      HO-1 protein expression in C2C12 myotubes; however, the conditioned medium from
      Akt1-overexpressing C2C12 myotubes increased HO-1 expression in endothelial
      cells. Cytokine array demonstrated that a panel of cytokine secretion was
      upregulated in Akt1-overexpressing C2C12 cells, suggesting paracrine interaction
      between muscle cells and endothelial cells and macrophages. CONCLUSIONS: Akt1
      mediated muscle growth improves blood flow recovery after hindlimb ischemia by
      enhancing HO-1 expression in neighboring cells.

PMID- 30101818
TI  - Leachables and cytotoxicity of root canal sealers.
AB  - This in vitro study aimed to detect leaching components from an epoxy resin- and
      a methacrylate-based endodontic sealer and correlate them to cytotoxicity induced
      by material extracts for up to 36 weeks. We qualitatively determined the
      substances released by aged AH Plus and RealSeal SE specimens at seven intervals
      between 0 and 36 weeks. Quantification was performed by ultra-performance liquid
      chromatography/mass spectrometry (UPLC/MS). We determined the viability of murine
      macrophage J774 cells after 24 h exposure to material extracts, at each interval,
      using a fluorescence staining/microscopy method. The leachables detected were 1
      adamantylamine and bisphenol A diglycidyl ether from AH Plus and N-(p-tolyl)
      diethanolamine and caprolactone-2-(methacryloyloxy) ethyl ester from RealSeal SE.
      The largest UPLC/MS chromatogram peak areas of the leachables were detected
      within 72 h. Induction of cytotoxicity after exposure to AH Plus and RealSeal SE
      extracts coincided with leachant detected within the first 72 and 24 h,
      respectively. The clinical impact of the cytotoxicity due to resin-based
      endodontic sealers is unknown.

PMID- 30101819
TI  - Salivary nitrate-nitrite conversion capacity after nitrate ingestion and
      incidence of Veillonella spp. in elderly individuals.
AB  - Dietary nitrate has several beneficial effects, including blood pressure
      reduction and improved oxygen consumption efficiency, but in order to do so it
      must first be reduced to nitrite by oral bacteria. Veillonella spp., a strictly
      anaerobic group, are the most prevalent nitrate-reducing bacteria in the oral
      cavity. In response to some early studies that have hinted at inter- and intra
      individual variation in salivary nitrate-nitrite conversion capacity, the purpose
      of the present study was to investigate the incidence of and variation in the
      Veillonella species V. atypica, V. dispar, and V. rogosae by direct PCR and to
      assess salivary nitrate-nitrite conversion capacity and its reproducibility after
      dietary nitrate consumption in 24 elderly individuals. V. atypica, V. dispar, and
      V. rogosae were detected in 10 (41.7%), 24 (100%), and 14 (58.3%) participants,
      respectively. The coefficients of correlation between the first and second
      experiments on increased nitrate/nitrite were 0.637 and 0.583, respectively, both
      of which were statistically significant (P < 0.01). In both experiments, 6
      participants produced relatively low levels of nitrite (<0.5 mM Delta nitrite)
      while 7 produced relatively high levels (>1.0 mM Delta nitrite). The data
      suggested that V. dispar was the most prevalent species, being present even in
      individuals producing low levels of salivary nitrite.

PMID- 30101820
TI  - Cellular responses of periodontal ligament stem cells to a novel synthesized form
      of calcium hydrogen phosphate with a hydroxyapatite-like surface for periodontal
      tissue engineering.
AB  - Calcium hydrogen phosphate with a hydroxyapatite-like surface (CHP-HA) is a novel
      synthesized compound designed to overcome the limitations of bioactive ceramics.
      It was originally applied as nano-sized HA strips covering core plates to enhance
      the degree of interfacial attachment. The objective of the present study was to
      examine the cellular attachment, proliferation, and osteogenic differentiation of
      periodontal ligament stem cells (PDLSCs) on a CHP-HA substrate in comparison with
      conventional nanohydroxyapatite (NanoHA). The PDLSCs were cultivated with either
      CHP-HA or NanoHA for cellular attachment, proliferation, and osteogenic
      differentiation assay. Osteogenic differentiation was examined using quantitative
      polymerase chain reaction and immunofluorescence after confirmation by Alizarin
      red staining. We found that between 14 and 21 days, CHP-HA exhibited a well
      organized matrix distribution, a high degree of cell proliferation, and a high
      level of Alizarin red staining in comparison to NanoHA. Expression of all the
      osteogenic markers examined was increased significantly relative to NanoHA at 14
      days, but no significant differences in some osteogenic genes were found at 21
      days. Immunofluorescence revealed stronger staining in the CHP-HA group. In
      conclusion, PDLSCs cultivated with this novel CHP-HA show enhanced cellular
      responses. We propose that CHP-HA may be a promising alternative biomaterial for
      periodontal tissue engineering.

PMID- 30101821
TI  - Influences of mechanical barrier permeability on guided bone augmentation in the
      rat calvarium.
AB  - We used radiological and histological analyses to evaluate the effects of
      mechanical barrier permeability in a rat model of calvarial guided bone
      augmentation (GBA). The calvaria of 20 rats were exposed, and one of four types
      of plastic caps (an occlusive cylindrical plastic cap; a plastic cap with no top;
      a plastic cap with three holes; and a plastic cap with four holes) was randomly
      placed on both sides. Newly generated bone in the plastic caps was evaluated with
      micro-computed tomography (micro-CT) and histological analysis. Micro-CT
      volumetric analysis and decalcified hematoxylin and eosin-stained sections showed
      that GBA barrier permeability was inversely associated with the quantity of
      augmented bone obtained. Masson's trichrome staining showed that collagen in
      newly generated bony tissue was more mature in plastic caps with three holes than
      in those with more-permeable or more-occlusive barriers. Bone augmentation was
      inhibited in specimens exhibiting invasion of soft tissue through penetrating
      holes, and barrier permeability was associated with the quantity of augmented
      bone developed. In conclusion, moderate barrier permeability is optimal for
      development of mature augmented bone.

PMID- 30101822
TI  - Expression of silent information regulator 2 homolog 1 (SIRT1) in periapical
      granulomas.
AB  - Silent information regulator 2 homolog 1 (SIRT1) inhibits oxidative injury and
      has anti-inflammatory effects. SIRT1 may be involved in healing of periapical
      periodontitis; however, SIRT1 expression in periapical periodontitis lesions has
      not been investigated. This study evaluated SIRT1 expression and a marker of
      oxidative stress-8-hydroxy-2'-deoxyguanosine (8-OHdG)-in periapical granulomas.
      First, we used real-time polymerase chain reaction to determine whether U-937
      monocytes express SIRT1. U-937 cells treated with the SIRT1 activator resveratrol
      exhibited the highest SIRT1 mRNA level after 6-h incubation. By contrast,
      treating cells with the SIRT1 inhibitor sirtinol returned SIRT1 expression level
      to that of the control. In addition, immunocytochemical analysis using cytospin
      specimens showed that U-937 cells co-expressed SIRT1 and Ki-67. Dual-color
      immunofluorescence imaging showed that round cells in periapical granulomas co
      expressed SIRT1 and 8-OHdG; however, neither was expressed in healthy gingival
      tissues. The number of 8-OHdG-expressing cells was significantly greater than the
      number of SIRT1-expressing cells. Our findings suggest that macrophages express
      SIRT1 and that wound healing in periapical granulomas is enhanced by a SIRT1
      mediated reduction in the level of oxidative stress.

PMID- 30101823
TI  - Continuous-Flow Left Ventricular Assist Device Therapy in Adults with
      Transposition of the Great Vessels.
AB  - An increasing number of children with congenital heart disease are surviving into
      adulthood and subsequently developing end-stage heart failure. Two example
      populations are adults who have been previously operated on for congenitally
      corrected transposition of the great arteries (CCTGA) and transposition of the
      great arteries (TGA). Implantation of a continuous flow left ventricular assist
      device (CF-LVAD) in these patients can present unusual anatomical and physiologic
      challenges. In this report, we describe outcomes of CF-LVAD implantation in three
      such patients. These cases demonstrate the feasibility of implanting a CF-LVAD in
      patients who have undergone surgery for CCTGA and/or TGA.

PMID- 30101824
TI  - Bolus administration of ephedrine and etilefrine induces transient vasodilation
      just after injection in combined epidural and general anesthesia patients: A
      randomized clinical study.
AB  - Hypotension commonly accompanies combined epidural and general anesthesia, and
      intravenous bolus ephedrine and etilefrine are widely used to correct
      hypotension. We have noticed that systemic vascular resistance (SVR) transiently
      decreases just after intravenous bolus administration of these drugs. The goal of
      the present study was to investigate whether bolus administration of these drugs
      decrease SVR just after intravenous administration in combined epidural and
      general anesthesia patients. We investigated 40 patients who were scheduled for
      elective abdominal surgery. Patients were chosen as subjects if their systolic
      arterial pressure decreased by 20% or to <100 mmHg at 30 min after the induction
      of general anesthesia. Baseline hemodynamic values were recorded, and after
      ephedrine 10 mg injection or etilefrine 2 mg injection (equipotent), the
      parameters were recorded again at 0.5 min and once each min for the next 5 min
      thereafter. The 40 patients were enrolled into the ephedrine (n = 20) or
      etilefrine (n = 20) treatment groups. Patient characteristics were comparable in
      both groups. After ephedrine injection, SVR decreased significantly at the 1-min
      time point, whereas after etilefrine injection, SVR decreased significantly at
      the 0.5- to 2-min time points compared with baseline values. SVR at the 0.5- to 1
      min time points was lower in the etilefrine versus the ephedrine group. Both
      drugs transiently decreased SVR after intravenous injection, but etilefrine
      decreased SVR much more than ephedrine, indicating that more vasodilation
      occurred after the injection of etilefrine than after ephedrine. It is thus
      important to recognize the different characteristics of these drugs.

PMID- 30101825
TI  - Spectroscopic methodologies and molecular docking studies on the interaction of
      the soluble guanylate cyclase stimulator riociguat with human serum albumin.
AB  - Interaction of riociguat with human serum albumin (HSA) is extremely important in
      understanding the drug's disposition and efficiency. In the current study, the
      binding of riociguat to HSA was explored using spectroscopic methods and
      molecular docking. The quenching constant, the binding constant, the number of
      binding sites, thermodynamic parameters, and the secondary structure of protein
      were determined. A fluorescence study revealed that riociguat quenched HSA
      fluorescence via static quenching with a binding constant of 1.55 * 104 L mol-1
      at 298 K. The calculated thermodynamic parameters indicated that the binding
      process was spontaneous and that the main interaction force was hydrophobic
      interaction. Site marker competitive binding experiments and molecular docking
      studies suggested that riociguat was inserted into the subdomain IIA (site I) of
      HSA. Alterations in the protein secondary structure after drug complexation were
      predicted. Results indicated that the protein a-helix structure increased with an
      increasing concentration of riociguat. This indicated that a riociguat-HSA
      complex was formed and that the protein secondary structure was altered by the
      addition of riociguat.

PMID- 30101826
TI  - Correlation of genetic diversity between hosts and parasites in Entamoeba
      nuttalli isolates from Tibetan and rhesus macaques in China.
AB  - Entamoeba nuttalli infection is prevalent in captive and wild macaques. Recent
      studies have suggested that genotypes of E. nuttalli isolates are correlated with
      the geographical distribution of host macaques. Correlation of amoebic genotypes
      with genetic diversity of host macaques was analyzed in present study. Sixty
      fresh stool samples were obtained from wild Tibetan macaques living in Mount
      Huang (HS) of the An-hui Province in China. PCR analysis revealed that the most
      prevalent Entamoeba species was E. chattoni (E. polecki ST2) (86.7%) followed by
      E. nuttalli (58.3%) and E. coli (25%). Six E. nuttalli HS isolates were
      successfully cultured. The tRNA-linked short tandem repeat (STR) loci and serine
      rich protein gene of E. nuttalli isolates from four different regions of China
      (Mount Long-hu, Gui-yang, Mount E-mei, and HS, the former three isolates were
      obtained in previous studies) were studied and high numbers of polymorphisms were
      detected. When genetic diversity of different populations of E. nuttalli isolates
      was compared with geographical distance, an r2 value of 0.919 was assigned by a
      Mantel test based on the tRNA-STR loci. In host macaques, the mtDNA HVS-I gene
      was also highly polymorphic in each of the genomes. Multiple regression analysis
      using E. nuttalli tRNA-STR loci genetic, macaque mtDNA HVS-I gene, and geographic
      distances showed an r2 value of 0.943, indicating that a higher relevance was
      demonstrated when geographic and host gene factors were considered. Analysis of
      genetic factor of host would benefit for better understanding of the evolution of
      E. nuttalli.

PMID- 30101827
TI  - Age-Related Declines in Executive Function and Cerebral Oxygenation Hemodynamics.
AB  - Cerebral hemodynamics plays an important role in cognitive performance, and as
      such, age-related cognitive dysfunction and cerebral hypoperfusion increase the
      risk of dementia. However, age-related changes in cerebral oxygenation and
      cognitive function remain unclear. The aim of this study was to investigate age
      related declines in cerebral oxygenation and executive function cross
      sectionally. Ninety-eight healthy Japanese adults (age range: 23-79 years; 40
      males, 58 females) participated in the present study using local advertisements.
      The participants were divided into 4 age groups: young (20-39 years; M15/F7), 50s
      (50-59 years; M10/F12), 60s (60-69 years; M9/F31), and 70s (70-79 years; M6/F8).
      We measured oxygenated hemoglobin (oxy-Hb) signal change in the prefrontal cortex
      during the Stroop task, and calculated Stroop interference time in cross
      sectional design. This test is widely used to measure the ability to properly
      control attention and behavior in executing tasks, and to evaluate executive
      functions mainly associated with the prefrontal cortex. Oxy-Hb signal changes in
      the left prefrontal cortex in the 60s and 70s groups were significantly lower
      than those in the young group (both P < 0.05). Additionally, Stroop interference
      time was significantly longer in the 60s and 70s groups than in the young group
      (both P < 0.05). Furthermore, differences in oxy-Hb signal change between the
      left and right prefrontal cortex were evident only in the young group. These
      results suggest that the age-related decrease in executive function is associated
      with decrease in the cerebral oxygenation hemodynamics in the left prefrontal
      cortex.

PMID- 30101828
TI  - Molecular detection and phylogenetic analysis of tick-borne pathogens in wild
      Korean water deer and farmed elk in Gyeongbuk and Gangwon Provinces of Korea.
AB  - The purpose of this study was to assess tick-borne pathogenic infections in 42
      wild Korean water deer (KWD) and 26 farmed elk in the Gyeongbuk and Gangwon
      Provinces of Korea. Among the 42 wild KWD tested, the eighteen (42.9%) and five
      (11.9%) samples tested positive for Anaplasma phagocytophilum and A. bovis,
      respectively, by PCR and DNA sequencing. All positive samples were only from wild
      KWD. All samples were negative for other tick-borne pathogens tested. Detected
      16S rRNA sequences of A. phagocytophilum and A. bovis showed 98.6-99.8% and 94.4
      100% identity to those of sequences in GenBank, respectively. Because few studies
      have examined tick-borne pathogens in wild animals, appropriate control programs
      and studies are needed to prevent pathogen transmission.

PMID- 30101829
TI  - Comparison of the microdrop and minimum volume cooling methods for vitrification
      of porcine in vitro-produced zygotes and blastocysts after equilibration in low
      concentrations of cryoprotectant agents.
AB  - We compared the efficacy of the microdrop and minimum volume cooling (MVC)
      methods for the vitrification of in vitro-produced porcine zygotes and
      blastocysts after equilibration in low concentrations of cryoprotectant agents.
      Zygotes and blastocysts were equilibrated in 2% (v/v) ethylene glycol and 2%
      (v/v) propylene glycol for 13-15 min. Then, they were vitrified in a medium
      comprised of 17.5% ethylene glycol, 17.5% propylene glycol, 0.3 M sucrose, and 50
      mg/ml polyvinylpyrrolidone either by either dropping them directly into liquid
      nitrogen (microdrop method) or placing them on Cryotop sheets in a minimum volume
      of medium and plunging into liquid nitrogen (MVC method). Both zygotes and
      blastocysts were successfully vitrified. For the vitrification of zygotes, the
      MVC and microdrop methods were equally effective; however, for blastocyst
      vitrification, MVC was superior. For both methods, the vitrification of zygotes
      produced higher-quality embryos than the vitrification of blastocysts.

PMID- 30101830
TI  - Design of a Novel Apparatus to Enrich Analytes via a Diffuse- Evaporation Process
      for HPLC-FTIRAnalysis.

PMID- 30101832
TI  - Lipidomic Profiling on Oxidized Phospholipids in Type 2 Diabetes Mellitus Model
      Zebrafish.
AB  - Type 2 diabetes mellitus is a serious metabolic disorder in the world. Oxidative
      stress, as a key role on the pathogenesis of diabetes, also results in the
      oxidation of phospholipids. However, studies on phospholipid oxidation in
      diabetes, especially directly focusing on oxidized and degraded phospholipid
      species, are quite limited. In this study, phospholipid profiles of diabetic
      zebrafish plasma were characterized by LC-HRMS and MS/MS, and the total amounts
      of each lipid class were compared. Furthermore, the key molecular species as
      biomarkers in distinguishing control and diabetic samples were investigated by
      orthogonal partial least squares discriminant analysis. Among the identified 114
      phospholipid species in total, there were 11 hydroperoxides, 7 aldehydes, and 19
      lysophospholipids found significantly elevated along with the increasing blood
      glucose, which were known as oxidation or degradation products. Furthermore,
      lysophosphatidylcholine 20:5 and lysophosphatidylcholine 22:6 were assessed as
      potential biomarkers in diabetic zebrafish. The current work would not only help
      to gain further insights into diabetes, but also contribute to find new clinical
      parameters for the screening of the promising antioxidant agents for its
      therapies.

PMID- 30101831
TI  - An Effective Capillary Valve Based on Micro-hole Array for Microfluidic Systems.
AB  - With the development of microfluidic systems for portable devices where the
      capillary force as the driving force drove the liquid in a microchannel. An
      effective capillary microvalve based on a micro-hole array is proposed in this
      paper for the purpose of good performance, and programmable control, and easy-to
      fabricate. The Wenzel model was used to slow down the velocity of fluid flow. The
      microvalve was made by a hot-embossing and hot-bonding process. The valve
      function was assessed by liquid flowing experiments. The results showed that the
      valve employs an abruptly changing contact angle to slow down the fluid flow. The
      controlling time is approximately 177 - 213 s. The best control effect was
      obtained when the contact angle equaled to 90 degrees . The effect of the
      roughness of the microvalve was also evaluated. Therefore, this work has a great
      potential and broad prospect for both research and applications in microfluidic
      systems, such as the portable devices in the medical testing field.

PMID- 30101833
TI  - Nanostructured Porous Electrodes by the Anodization of Gold for an Application as
      Scaffolds in Direct-electron-transfer-type Bioelectrocatalysis.
AB  - In this study, nanostructured porous gold electrodes were prepared by the
      anodization of gold in the presence of oxalic acid or glucose as a reductant, and
      applied as scaffolds for direct electron transfer (DET)-type bioelectrocatalysis.
      Gold cations generated in the anodization seem to be reduced by the reductant to
      construct a porous gold structure. The DET-type performance of the electrode was
      examined using two DET-type model enzymes, bilirubin oxidase (BOD) and peroxidase
      (POD), for the four-electron reduction of dioxygen and the two-electron reduction
      of peroxide, respectively. BOD and POD on the anodized porous gold electrodes
      exhibited well-defined sigmoidal steady-state waves corresponding to DET-type
      bioelectrocatalysis. Scanning electron microscopy images revealed sponge-like
      pores on the electrodes. The anodized porous gold electrodes demonstrate promise
      as scaffolds for DET-type bioelectrocatalysis.

PMID- 30101834
TI  - Clinicopathologic characteristics of patients with tuberculosis and
      schizophrenia.
AB  - The clinicopathologic characteristics of patients with tuberculosis (TB) and
      schizophrenia are unclear. In order to facilitate early diagnosis and prompt
      treatment, a retrospective study was conducted in China. Subjects were 54
      consecutive patients who were seen between October 2006 and December 2015. Data
      on demographic characteristics, underlying diseases, clinical features, and
      outcomes were collected from medical records using a standardized data collection
      form. Acid-fast bacilli were detected at a rate of 26.9%, a mycobacterial culture
      was positive at a rate of 35.4%, and a real-time polymerase chain reaction was
      positive for TB at a rate of 35%. Of the 54 patients, i) 44 (81.5%) had symptoms
      for at least 2 weeks; ii) 10 (18.5%) were transferred from a local psychiatric
      hospital, and 23 (42.6%) were transferred at least twice before arriving at this
      Hospital. Unfortunately, the outcome was not successful in these patients, 18
      patients (33.3%) had to be retreated, 7 patients (13.0%) had their care
      interrupted because their schizophrenia worsened. The current study found that
      the management of TB in patients with schizophrenia poses several challenges.
      These include delays in diagnosis and treatment of TB, inefficient strategies for
      control of TB transmission in psychiatric hospitals, the need for a psychiatrist
      to be involved in care, and a high rate of retreatment.

PMID- 30101835
TI  - Association between the MVK rs2287218 SNP and the risk of coronary heart disease
      and ischemic stroke: A case-control study.
AB  - The association between the mevalonate kinase gene (MVK) single nucleotide
      polymorphism (SNP) and serum lipid levels has been detected in several previous
      genome-wide association studies, but the results are inconsistent. In addition,
      it is still unclear whether the loci indentified exert the similar effect on the
      susceptibility of coronary heart disease (CHD) or ischemic stroke (IS).
      Therefore, the present study was undertaken to detect the association between the
      MVK rs2287218 SNP and serum lipid levels, the susceptibility of CHD and IS in a
      Southern Chinese Han population. The genotypes of the SNP in 1764 unrelated
      subjects (CHD, 583; IS, 555; and healthy controls, 626) were determined by the
      Snapshot technology. The genotypic and allelic frequencies were different between
      CHD and control subjects (P <= 0.013 for each), or between IS and control groups
      (P < 0.01 for each). The T allele carriers had an increased risk of CHD and IS
      (CHD: OR = 1.674, 95%CI = 1.25-2.25, P = 0.001 for CT/TT vs. CC genotypes; OR =
      1.595, 95%CI = 1.23-2.07, P < 0.001 for T vs. C alleles; IS: OR = 1.890, 95%CI =
      1.36-2.47, P = 0.001 for CT/TT vs. CC genotypes; OR = 1.829, 95%CI = 1.38-2.42, P
      < 0.001 for T vs. C alleles). The T allele carriers in healthy controls had lower
      serum high-density lipoprotein cholesterol (HDL-C) levels than the T allele non
      carriers (P = 0.013). These findings suggest that the MVK rs2287218 SNP is likely
      to increase the risk of CHD and IS by decreasing serum HDL-C levels in our study
      populations.

PMID- 30101836
TI  - Clinical significance of respiratory compensation during exercise testing in
      cardiac patients.
AB  - Ventilation (VE) increases linearly with the increase of carbon dioxide output
      (VCO2) during cardiopulmonary exercise testing. VE-VCO2 slope rises in parallel
      with exercise intensity, reaches a turning point (called the RC point), then
      steepens because of respiratory compensation for lactic acidosis. While this RC
      point can be identified universally, it is undetectable in some patients. In this
      study we evaluated whether the respiratory compensation during exercise testing
      has clinical significance in cardiac patients. In total, 152 cardiac patients
      with a respiratory exchange ratio at peak exercise (peak R) of between 1.10 and
      1.20 were enrolled. Cardiopulmonary parameters were compared between patients who
      manifested the RC point (n = 118) and those who did not (n = 34). The peak R did
      not significantly differ between these two groups. Compared to the patients
      without the RC point, those with the RC point had a higher oxygen uptake at peak
      exercise (peak VO2) (20.2 +/- 5.3 vs 13.6 +/- 3.4 mL/min/kg, p < 0.001), higher
      anaerobic threshold (AT) (12.4 +/- 3.2 vs 9.2 +/- 2.3 mL/min/kg, p < 0.001), and
      lower VE-VCO2 slope (31.7 +/- 5.8 vs 37.8 +/- 9.6, p = 0.001). Brain natriuretic
      peptide (BNP) tended to be lower in the patients with the RC point (175.4 +/-
      364.7 vs 327.9 +/- 381.1 pg/mL, p = 0.067). Peak VO2, the marker of
      cardiopulmonary function, was found to be the independent predictor of the
      presence of the RC point. The present findings suggest that the phenomenon of
      respiratory compensation during heavy exercise indicates better cardiopulmonary
      function in cardiac patients within a prescribed range of effort.

PMID- 30101837
TI  - Dihydroartemisinin represses osteoclastogenesis of bone marrow macrophages
      through reduced NFATc1 expression and impaired phosphorylation of IkappaBalpha.
AB  - Osteoclasts are multinucleated bone resorbing cells whose differentiation is
      regulated by several important signaling pathways. Several lines of evidence
      indicate that dihydroartemisinin (DHA), an anti-malarial drug, inhibits
      osteoclast differentiation with little cytotoxicity. However, the detailed
      inhibitory mechanisms of DHA on osteoclastogenesis from native cells remain to be
      elucidated. In this study, we investigated the effects of DHA on the
      differentiation of bone marrow-derived macrophages into osteoclasts. DHA
      inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced
      osteoclast formation and its bone resorbing activity. Mechanistically, DHA
      treatment markedly abolished phosphorylation of IkappaBalpha, and slightly
      affected a p38 MAPK dependent pathway. Moreover, DHA treatment induced down
      regulation of nuclear factor of activated T cells cytoplasmic-1 (NFATc1), a
      master regulator for osteoclast differentiation and its target proteins, such as
      Src and cathepsin K. These results indicate that DHA represses RANKL-induced
      osteoclastogenesis of bone marrow macrophages through reduced NFATc1 expression
      and impaired phosphorylation of IkappaBalpha.

PMID- 30101838
TI  - Intracellular localization of GGA accessory protein p56 in cell lines and central
      nervous system neurons.
AB  - Adaptor protein complex-1 (AP-1) and Golgi associated, gamma-adaptin ear
      containing, Arf binding proteins (GGAs) are clathrin adaptors that regulate
      membrane trafficking between the trans-Golgi network (TGN) and endosomes. p56 is
      a clathrin adaptor accessory protein that may modulate the function of GGAs in
      mammalian cell lines. However, the precise relationship between p56 and the three
      GGAs (GGA1-3), as well as the physiological role of p56 in tissue cells, remain
      unknown. To this end, we generated an antibody against p56 and determined its
      cellular localization. In ARPE-19 cells and mouse embryonic fibroblasts, p56 was
      found to be localized as fine puncta in the TGN. Interestingly, the depletion of
      each clathrin adaptor by RNAi revealed that this localization was dependent on
      the expression of GGA1, but not that of GGA2, GGA3, or AP-1. Using
      immunohistofluorescence microscopy in the mouse central nervous system (CNS), p56
      was clearly detected as scattered cytoplasmic puncta in spinal motor neurons,
      cerebellar Purkinje cells, and pyramidal neurons of the hippocampus and cerebral
      cortex. Moreover, double labeling with organelle markers revealed that the
      majority of these puncta were closely associated with the TGN; however, a small
      fraction was associated with endosomes or lysosomes in spinal motor neurons.
      Collectively, these results indicate a functional association of p56 with GGA1,
      suggesting an important role of p56 in larger CNS neurons.

PMID- 30101839
TI  - Neuron-like cells in the chick spinal accessory lobe express neuronal-type
      voltage-gated sodium channels.
AB  - Ten pairs of protrusions, called accessory lobes (ALs), exist at the lateral
      sides of the avian lumbosacral spinal cord. Histological evidence indicates that
      neuron-like cells gather in the ALs, and behavioral evidence suggests that the
      ALs act as a sensory organ of equilibrium during bipedal walking. Recently, using
      an electrophysiological method, we reported that cells showing Na+ currents and
      action potentials exist among cells that were dissociated from the ALs. However,
      it was unclear which isoforms of the voltage-gated sodium channel (VGSC) are
      expressed in the ALs and whether cells having neuronal morphology in the ALs
      express VGSCs. To elucidate these points, RT-PCR and immunohistochemical
      experiments were performed. In RT-PCR analysis, PCR products for Nav 1.1-1.7 were
      detected in the ALs. The signal intensities of the Nav 1.1 and 1.6 isoforms were
      stronger than those of the other isoforms. We confirmed that an antibody raised
      against an epitope peptide of the rat VGSC had cross-reactivity to chick tissues
      by Western blotting, and we performed immunofluorescence staining using the
      antibody. The AL contained cells having neuron-like morphology and VGSC-like
      immunoreactivity at their cytoplasm and/or cell membranes. Filament-like
      structures showing GFAP-like immunoreactivity infilled intercellular spaces. The
      VGSC- and GFAP-like immunoreactivities did not overlap. These results indicate
      that the neuronal isoforms of the VGSC are mainly expressed in the AL and that
      the neuron-like cells in the ALs express VGSCs. Our findings indicate that AL
      neurons generate action potentials and send sensory information to the motor
      systems on the contralateral side of the spinal segment.

PMID- 30101840
TI  - Differential effects of depot formulations of GnRH agonist leuprorelin and
      antagonist degarelix on the seminiferous epithelium of the rat testis.
AB  - Despite their pharmacologically opposite actions, long-acting depot formulations
      of both GnRH agonists and antagonists have been clinically applied for treatment
      of androgen-sensitive prostate cancer. Sustained treatment with GnRH analogues
      commonly suppresses both the synthesis and release of gonadotropins, leading to
      depletion of testicular testosterone. To clarify the underlying differences in
      the effects of GnRH agonists and antagonists on spermatogenesis, we compared
      histological changes in the seminiferous epithelium after administration of depot
      formulations of GnRH agonist leuprorelin and antagonist degarelix to male rats.
      Testicular weight had markedly declined by 28 days after administration of both
      GnRH analogues, although the testicular weight was decreased more promptly by
      leuprorelin compared with degarelix. Shortly after administration, massive
      exfoliation of premature spermatids and anomalous multinucleated giant cells was
      observed in seminiferous tubules of leuprorelin-treated rats, probably via the
      initial hyperstimulatory effects on the hypothalamic-pituitary-testicular axis,
      whereas no discernible changes were found in those of degarelix-treated rats.
      Long term treatment with both types of GnRH analogues similarly induced a marked
      reduction in the height of the epithelium and deformation of apical cytoplasm in
      Sertoli cells, resulting in premature detachment of spermatids from the
      epithelium. Lipid droplets had accumulated progressively in Sertoli cells,
      especially in those of degarelix-treated rats. These findings clearly demonstrate
      the differences in the effects of GnRH agonists and antagonists on the
      spermatogenic process. This study suggests that an appropriate choice of GnRH
      analogues is necessary to minimize their adverse effects on spermatogenesis when
      reproductive functions should be preserved in patients.

PMID- 30101841
TI  - Analgesic effect of mineral cream containing natural spa minerals for use on the
      skin.
AB  - Previous studies have shown that dissolved substances in some natural hot springs
      have analgesic/anti-nociceptive and anti-inflammatory actions. However, the
      mechanisms underlying how such dissolved substances exert these actions are not
      fully understood. In the present study on mice, we examined the analgesic/anti
      nociceptive and anti-inflammatory properties of a mineral cream containing
      natural hot spring ingredients. The anti-nociceptive effects of the mineral cream
      were assessed by using the von Frey test. Application of the mineral cream to the
      hind paw of mice produced a significant anti-nociceptive effect compared to
      control. The anti-nociceptive effects of the mineral cream were also assessed
      following the injection of complete Freund's adjuvant (CFA) into the hind paws of
      mice after pre-treatment for one or four weeks with the mineral cream.
      Histological experiments with light microscopy showed that the mineral cream did
      not reduce inflammation caused by the CFA treatment. In addition, the mineral
      cream did not inhibit oxidative stress as evidenced by increased levels of
      oxidative metabolites (d-ROMs) and biological anti-oxidant potential (BAP). These
      results suggest that the mineral cream does not exert a protective effect against
      inflammation, and that the constituents of the mineral cream may produce their
      anti-nociceptive effects transdermally via different mechanisms including the
      nervous system.

PMID- 30101842
TI  - Alterations of Cardiac KATP Channels and Autophagy Contribute in the Late
      Cardioprotective Phase of Exercise Preconditioning.
AB  - The cardiac effects of exercise preconditioning (EP) are well established;
      however, the mechanisms involving cardiac ATP-sensitive potassium channel (KATP
      channel) subunits and autophagy are yet to be fully established. The present work
      aims to investigate the alterations of cardiac KATP channel subunits Kir6.2,
      SUR2A, and autophagy-related LC3 during the late cardioprotective phase of EP
      against exhaustive exercise-induced myocardial injury. Rats run on treadmill for
      four running time intervals, each with 10 minutes running and rest. Exhaustive
      exercise was performed 24 h after EP. Cardiac biomarkers, cTnI and NT-proBNP,
      along with the histological stain, were served as indicators of myocardial
      injury. Cardiac KATP channel subunits Kir6.2 and SUR2A were analyzed in this
      study, and autophagy was evaluated by LC3. The results revealed that EP reduced
      the exhaustive exercise-induced high level of serum cTnI and myocardial
      ischemia/hypoxia; however, it did not reveal any changes in the serum NT-proBNP
      level or cardiac BNP. Cardiac SUR2A mRNA significantly upregulated during the
      exhaustive exercise. The high levels of Kir6.2, SUR2A, LC3IIpuncta and LC3II
      turnover observed after exhaustive exercise were significantly mitigated by EP in
      the late phase. These results suggest that EP alleviates myocardial injury
      induced by exhaustive exercise through the downregulation of cardiac KATP
      channels and autophagy.

PMID- 30101843
TI  - Utilization of Emergency and Hospitalization Care after Coronary Artery Bypass
      Surgery for Patients with Ischemic Heart Disease.
AB  - This retrospective follow-up study explored the status of patients with
      myocardial infarction with regard to the likelihood of being readmitted to the
      hospital within 30 days after undergoing coronary artery bypass surgery (CABG)
      and their survival status within one year of the procedure.The rate of
      readmission within 30 days was 10.7% (167/1,575), primarily due to surgical wound
      infection (11.3% of readmission cases), ischemic heart disease (10.3%), and heart
      failure (8.7%). The readmission group consisted mainly of older males with a high
      comorbidity index. No significant differences existed between the two groups with
      regard to case distribution, hospital level, tenure of physicians, or teaching
      status of the hospitals. Most subsequent emergency department visits one month
      after surgery involved older male patients with a high comorbidity index.
      Compared to patients in the non-emergency group, those in the emergency group had
      longer hospital stays but lower mortality rates. Males constituted a higher
      proportion of survivors at one year post CABG, with age and comorbidity index
      being the primary variables affecting the risk of death.The National Health
      Insurance may adopt the policy of increasing payments for medical institutions
      that avoid readmission within 30 days post CABG in order to encourage better
      patient care and avoid the costs associated with readmission.

PMID- 30101844
TI  - Postoperative Lung Perfusion with Anomalous Origin of One Pulmonary Artery from
      the Aorta.
AB  - Pulmonary artery damage is difficult to estimate in a patient with one pulmonary
      artery from the aorta, and the pulmonary artery of anomalous origin is usually
      damaged. We describe a newborn patient with anomalous origin of the right
      pulmonary artery from the aorta who presented with significant lung perfusion at
      the anastomotic site 6 months postoperatively; the left/right perfusion ratio was
      10:90 on a scintigram. The unbalanced left/right lung perfusion gradually
      improved over a number of years. In a newborn patient with anomalous origin of
      one pulmonary artery from the aorta, unbalanced lung perfusion may improve.

PMID- 30101845
TI  - The Adaptive Remodeling of the Anterior Mitral Leaflet and Chordae Tendineae Is
      Associated with Mitral Valve Function in Advanced Ischemic and Nonischemic
      Dilated Cardiomyopathy.
AB  - The degree or nature of functional mitral regurgitation (MR) is not necessarily
      correlated with the size or function of the left ventricle (LV). We hypothesized
      that the anatomical structure of the mitral valve (MV) complex might play a role
      in functional MR in ischemic or nonischemic dilated cardiomyopathy (DCM).The
      structure of the LV and MV complex in DCM patients (n = 29) was assessed using
      electrocardiogram-gated 320-slice computed tomography and was compared with that
      in healthy patients (n = 12). Twenty-five DCM patients with mild or low MR (DCM
      lowMR) had markedly greater length, diameter, and sphericity index of the LV and
      a larger tenting area than the controls. The distance between the papillary
      muscle (PM) tip and the mitral annular plane was not different between DCM-lowMR
      and normal hearts despite the greater LV length observed in DCM-lowMR.
      Furthermore, DCM-lowMR had markedly longer chordae tendineae (DCM-lowMR: 24 [20
      26] mm; controls: 14 [13-16] mm; P < 0.01) and larger anterior leaflets (DCM
      lowMR: 30 [27-31] mm; controls: 22 [20-24] mm; P < 0.01), thus suggesting the
      adaptive remodeling of the MV complex. Four DCM patients with moderate-severe MR
      had unbalanced remodeling, such as excessive LV dilatation, short anterior mitral
      leaflets, and short chordae tendineae.The development of functional MR might be
      associated with the remodeling of LV and MV components, such as the PMs, chordae
      tendineae, or anterior MV leaflets. Detailed anatomical assessments of the LV and
      MV complex would contribute to the adequate staging of ischemic or nonischemic
      DCM.

PMID- 30101847
TI  - Relationship Between Serum Sodium Level Within the Low-Normal Range on Admission
      and Long-Term Clinical Outcomes in Patients with Acute Decompensated Heart
      Failure.
AB  - Although hyponatremia during hospitalization for acute decompensated heart
      failure (ADHF) is reportedly related with poor prognosis, the available data
      regarding the impact of serum sodium level within the low-normal range at
      admission on clinical events in patients with ADHF is limited.We studied eligible
      patients admitted to our institution in 2007-2011. All the patients were
      categorized into 3 groups according to the admission serum sodium levels of < 135
      mmol/L (hyponatremia), >= 135 and < 140 mmol/L (low-normal range), or >= 140
      mmol/L (normal range). The association between admission serum sodium levels and
      long-term clinical events, a composite of all-cause deaths and re
      hospitalizations for ADHF, was assessed by multivariable Cox proportional
      analysis.Of the 584 eligible patients, 208 (35.6%) were in the low-normal range
      and 99 (16.9%) had hyponatremia on admission. On multivariable analysis, compared
      with those with a sodium level >= 140 mmol/L, patients with hyponatremia were at
      increased risk for clinical events (hazard ratio [HR], 1.53; P = 0.041), whereas
      the HR of those in the low-normal range was attenuated and insignificant (HR,
      1.08; P = 0.625). However, the HR of each category increased significantly as
      sodium level decreased (P value for HR trend, 0.024). In addition, when serum
      sodium level was treated as a continuous variable, the lower the serum sodium
      level, the greater the risk of clinical events (P = 0.012). The cut-off value of
      serum sodium level to predict mortality was < 138 mmol/L.In conclusion, a low
      serum sodium level on admission for ADHF, even if low-normal, can increase the
      risk of long-term mortality and/or re-hospitalization for ADHF.

PMID- 30101846
TI  - Screening and Function Analysis of MicroRNAs Involved in Exercise Preconditioning
      Attenuating Pathological Cardiac Hypertrophy.
AB  - Exercise preconditioning (EP) attenuates pathological cardiac hypertrophy by
      increasing the functional capacity of the cardiovascular system; however, the
      underlying molecular mechanisms remain unclear. MicroRNAs (miRNAs) play important
      roles in various physiological and pathological processes by regulating the
      expression of the targeted gene. In this study, we aimed to screen the miRNAs
      involved in EP-attenuating pathological cardiac hypertrophy. The histological and
      echocardiographic parameters assessment showed that pathological cardiac
      hypertrophy induced by transverse aortic constriction (TAC) was significantly
      alleviated in EP treated rats. The left ventricular tissues (n = 3) from Sham,
      TAC and EP + TAC groups were subjected to small RNA deep sequencing. A total of
      570 known mature miRNAs and 530 putative novel miRNAs were detected. DEGseq
      analysis showed that there were 37 and 88 differentially expressed miRNAs in the
      comparisons of TAC versus Sham and EP + TAC versus TAC, respectively. Among them,
      EP treatment could relieve the expression changes of 32 miRNAs, which were
      supposed to be involved in EP-attenuating pathological cardiac hypertrophy. After
      miRNAs target genes prediction by miRDB algorithm, pathway analysis showed that
      the most frequently represented pathways were involved in Calcium signaling
      pathway and MAPK signaling pathway. The results would provide valuable clues to
      finding therapeutic targets for the treatment of pathological cardiac
      hypertrophy.

PMID- 30101848
TI  - Regular Treatment Strategy with a Large Amount of Carvedilol for Heart Failure
      Improves Biventricular Systolic Failure in a Patient with Repaired Tetralogy of
      Fallot.
AB  - It is widely known that beta-blockers exert beneficial effects on non-ischemic
      and ischemic systolic heart failure (sHF) in nonstructural hearts. However,
      whether beta-blockers exert similar effects on sHF associated with congenital
      heart disease (CHD), particularly in an anatomical right ventricle, remains under
      debate.Here we report the case of an adult man with repaired tetralogy of Fallot
      suffering from biventricular heart failure. Treatment with carvedilol directly
      improved the systolic function of the right and left ventricles. This case report
      strongly suggests there is potential for carvedilol to exert a beneficial effect
      on heart failure in CHD. The appropriate titration of carvedilol and patient
      follow-up for long-term effects are important when treating adult patients with
      CHD with beta-blockers.

PMID- 30101850
TI  - Candidacy for a Subcutaneous Implantable Cardioverter Defibrillator in Patients
      with Cardiac Resynchronization Therapy.
AB  - In patients requiring an implantable cardioverter defibrillator (ICD), the
      combined use of a prior pacemaker and a subcutaneous ICD (S-ICD) could be an
      alternative treatment option to implantation of new leads or upgrading of
      pacemakers to an ICD if vascular access is limited. Here, we assessed the
      prevalence of S-ICD's eligibility according to surface electrogram screening in
      those receiving cardiac resynchronization therapy (CRT). S-ICD's eligibility was
      assessed in patients with a CRT pacemaker or a CRT defibrillator using the S-ICD
      template screening tool. Eligibility was defined as fulfillment of the template
      in both supine and upright positions in one or more leads during biventricular
      pacing. Among 44 patients (34 men, age: 67 +/- 12), 36 (82%) were found to be
      eligible. The T/QRS amplitude ratio in lead II was significantly lower in those
      who were eligible (0.31 +/- 0.16 versus 0.44 +/- 0.18 in the ineligible group, P
      = 0.04). The lead position, underlying disease, and other electrocardiographic
      findings were not different between those who were eligible and those who were
      not. The majority of patients with biventricular pacing were eligible for S-ICD
      based on current screening tests and may benefit from this treatment. Further
      study is required.

PMID- 30101849
TI  - The Comparison of Clinical Outcomes After Drug-Eluting Balloon and Drug-Eluting
      Stent Use for Left Main Bifurcation In-Stent Restenosis.
AB  - Increasing evidence is available for the use of percutaneous coronary
      intervention (PCI) in selected patients with unprotected left main (LM)
      bifurcation coronary lesions. However, little data have been reported on
      recurrent in-stent restenosis (ISR) for LM bifurcation lesions. The aim of this
      study was to evaluate the efficacy of a drug-eluting balloon (DEB) for LM
      bifurcation ISR compared with that of a drug-eluting stent (DES).Between December
      2011 and December 2015, 104 patients who underwent PCI for unprotected LM
      bifurcation ISR were enrolled. We separated the patients into 2 groups: (1) those
      underwent PCI with further DEB and (2) those underwent PCI with further DES.
      Clinical outcomes were analyzed.Patients' average age was 67.14 +/- 7.65 years,
      and the percentage of male patients was 76.0%. A total of 75 patients were
      enrolled in the DEB group, and another 29 patients were enrolled in the DES
      group. Similar target lesion revascularization (TLR) rate and recurrent
      myocardial infarction (MI) rate were noted for both groups. A significantly
      higher cardiovascular mortality rate was found in the DES group (10.7% versus 0%,
      P = 0.020), and a higher all-cause mortality rate was noted in the DES group
      (21.4% versus 6.8%, P = 0.067).It is feasible to use DEB for LM bifurcation ISR.
      When comparing DEB with DES, similar TLR rates were found, but lower recurrent MI
      and lower cardiovascular death were noted for DEB treatment.

PMID- 30101851
TI  - Randomized Trial of Effect of Urate-Lowering Agent Febuxostat in Chronic Heart
      Failure Patients with Hyperuricemia (LEAF-CHF).
AB  - Hyperuricemia is an independent predictor of mortality in patients with chronic
      heart failure. The aim of the study is to determine whether a urate-lowering
      agent febuxostat, an inhibitor of xanthine oxidase, may improve the clinical
      outcomes in chronic heart failure patients with hyperuricemia when compared to
      conventional treatment. This multicenter, prospective, randomized, open-label,
      blinded endpoint study with a follow-up period of 24 weeks will enroll 200
      Japanese chronic heart failure patients with hyperuricemia. The eligibility
      criteria include a diagnosis of chronic heart failure (New York Heart Association
      functional class II-III with a history of hospitalization due to worsening of
      heart failure within the last 2 years), reduced left ventricular systolic
      function (left ventricular ejection fraction < 40%) and increased plasma
      natriuretic peptide [plasma B-type natriuretic peptide (BNP) >= 100 pg/mL or N
      terminal pro BNP (NT-proBNP) >= 400 pg/mL], and hyperuricemia (serum uric acid
      >7.0 mg/dL and <= 10 mg/dL) at the screening visit. The primary outcome is the
      difference in the plasma BNP levels between the baseline and 24 weeks of
      treatment. The plasma BNP levels are measured in the central laboratory in a
      blinded manner. This study investigates the efficacy and safety of febuxostat in
      chronic heart failure patients with hyperuricemia.

PMID- 30101853
TI  - A Case of Aortic Stenosis with Serum IgG4 Elevation, and IgG4-Positive
      Plasmacytic Infiltration in the Aortic Valve, Epicardium, and Aortic Adventitia.
AB  - A 74-year-old man was admitted for preoperative screening of aortic stenosis.
      Five months before this admission, he was found to have elevated serum
      immunoglobulin G4 (IgG4; 2,010 mg/dL). Computed tomography (CT) showed a soft
      tissue mass surrounding the abdominal aorta, suggestive of IgG4-related
      periaortitis. CT coronary angiography showed perivascular thickening of the right
      coronary artery, and subsequent coronary angiography showed a multi-vessel
      disease. The patient underwent aortic valve replacement and coronary bypass
      surgery. Immunohistochemical analysis showed IgG4-positive plasmacytic
      infiltration in specimens from the aortic valve, epicardium, and aortic
      adventitia, suggestive of the possible role of IgG4-related immune inflammation
      for the pathogenesis.

PMID- 30101854
TI  - Right Ventricular Stroke Work Index.
AB  - Recently, long-term outcomes of pre-capillary pulmonary hypertension (PH) have
      been improved, whereas morbidity and mortality are still high because of right
      sided heart failure (HF). Right-sided HF is closely related to right ventricular
      (RV) function and hemodynamics such as RV stroke work index (RVSWI). However, the
      association between RVSWI and long-term outcomes in pre-capillary PH has not been
      well investigated. The aims of this study were to compare clinical
      characteristics between low RVSWI and high RVSWI and to investigate the
      association between low RVSWI and long-term outcomes in patients with pre
      capillary PH. We included patients admitted to diagnose and evaluate PH by right
      heart catheterization between 2007 and 2015. Patients with pre-capillary PH were
      divided into two groups according to the median value of RVSWI (low RVSWI group:
      RVSWI < 19.7 g?m/m2/beat; high RVSWI group: RVSWI >= 19.7 g?m/m2/beat). Kaplan
      Meier survival curves were applied to investigate whether the low RVSWI were
      associated with HF death or HF readmission in patients with pre-capillary PH. A
      total of 36 patients with pre-capillary PH who were diagnosed as pulmonary
      arterial hypertension (PAH) or chronic thromboembolic PH (CTEPH) were allocated
      into the low RVSWI group (n = 18) and high RVSWI group (n = 18). The event-free
      survival rate was significantly lower in the low RVSWI group as compared with the
      high RVSWI group (P = 0.02). In conclusion, lower RVSWI was significantly
      associated with HF death or HF readmission in patients with PAH or CTEPH.

PMID- 30101852
TI  - Chronic Pressure Overload Induces Cardiac Hypertrophy and Fibrosis via Increases
      in SGLT1 and IL-18 Gene Expression in Mice.
AB  - Increased gene expression levels of sodium-glucose cotransporter 1 (SGLT1) are
      associated with hypertrophic and ischemic cardiomyopathy. However, it remains
      unclear whether chronic pressure overload increases SGLT1 expression, which in
      turn induces hypertrophic cardiomyopathy. We hypothesized that pressure overload
      could increase SGLT1 gene expression, leading to the development of hypertrophic
      cardiomyopathy.To create pressure overload-induced cardiomyopathy, transverse
      aortic constriction (TAC) was performed in SGLT1-deficient (SGLT1-/-) and wild
      type (WT) mice. Six weeks after surgery, all mice were investigated. We observed
      a reduction of left ventricular fractional shortening and left ventricular
      dilatation in TAC-operated WT but not in TAC-operated SGLT1-/- mice. SGLT1,
      interleukin 18, connective tissue growth factor, and collagen type 1 gene
      expression levels were increased in TAC-operated WT mouse hearts compared with
      that of sham-operated WT mouse hearts. Moreover, heart/body weight ratio and
      ventricular interstitial fibrosis were increased in TAC-operated WT mice compared
      with that of sham-operated WT mice. Interestingly, these factors did not increase
      in TAC-operated SGLT1-/- mice compared with that of sham-operated WT and SGLT1-/-
      mice. Phenylephrine, an adrenergic alpha1 receptor agonist, caused cardiomyocyte
      hypertrophy in neonatal WT mouse hearts to a significantly larger extent than in
      neonatal SGLT1-/- mouse hearts.In conclusion, the results indicate that chronic
      pressure overload increases SGLT1 and IL-18 gene expressions, leading to the
      development of hypertrophic cardiomyopathy. These results make SGLT1 a potential
      candidate for the therapeutic target for hypertension-induced cardiomyopathy.

PMID- 30101855
TI  - Outcomes in Patients with Critical Limb Ischemia due to Arteriosclerosis
      Obliterans Who Did Not Undergo Arterial Reconstruction.
AB  - The prevalence of arteriosclerosis obliterans (ASO) and critical limb ischemia
      (CLI) is currently increasing, and arterial reconstruction is often attempted to
      salvage the limb. Some patients cannot undergo attempted revascularization
      because of contraindications, and they only receive conservative treatment. In
      this study, we investigate the comorbidities and survival rates of patients with
      CLI who receive conservative treatment. Thirty-five patients with CLI due to ASO,
      who had not undergone revascularization surgery (C group), were enrolled. As
      controls, 136 patients with CLI due to ASO who did undergo revascularization (R
      group), mainly via bypass surgery, were enrolled. Coronary artery disease, heart
      failure, and respiratory dysfunction were factors indicating conservative
      treatment. Limb salvage rates and survival rates were not significantly different
      between the two groups. Patients who had survived for less than two years after
      surgery had a higher prevalence of chronic heart failure, cardiovascular disease,
      and end-stage renal disease compared to patients who had survived for more than
      two years. The use of statins, dual antiplatelets, aspirin, or warfarin did not
      influence whether a patient survived for longer than two years. 77% of patients
      survived for more than two years after receiving only conservative therapies.
      Surgical revascularization did not improve the prognosis of patients with CLI as
      compared with the conservative therapy. Clinicians might start with conservative
      treatment while considering other treatment options for patients with CLI.

PMID- 30101856
TI  - A Novel Bioabsorbable Sheet That Delivers NF-kappaB Decoy Oligonucleotide
      Restrains Abdominal Aortic Aneurysm Development in Rats.
AB  - For the suppression of inflammation in the aneurysm development, we focused on
      inhibition of an important transcription factor, nuclear factor-kappa B (NF
      kappaB), using a decoy strategy. We newly developed a novel bioabsorbable sheet
      that delivers NF-kappaB decoy oligodeoxynucleotide (ODN).We treated 5-week-old SD
      rats that were induced with abdominal aortic aneurysm (AAA) using 0.5 M CaCl2
      with an NF-kappaB decoy sheet. Four weeks after AAA induction, aortic tissue was
      excised for further examinations. We showed that this bioabsorbable sheet could
      deliver the decoy ODN into the target tissues and dissolve within a week.
      Treatment with the NF-kappaB decoy sheet reduced the aneurysm size compared with
      the controls. It also suppressed inflammation due to the effect of NF-kappaB
      decoy ODN. Immunohistochemistry revealed that the expression of CD31, CD4, and
      CD11b in the NF-kappaB decoy sheet group was significantly lower than in the
      control sheet group. The NF-kappaB decoy sheet was absorbed on the target
      tissue.We have revealed that the bioabsorbable sheet mediated decoy ODN is
      effective for transfection into target organs. We have also indicated that NF
      kappaB decoy ODN transfection using this sheet has the potential to suppress the
      dilatation of aneurysm. The bioabsorbable sheet mediated transfection of the
      decoy ODN can be beneficial for the clinical treatment of AAA and other NF-kappaB
      related cardiovascular diseases.

PMID- 30101860
TI  - [Central neuronal circuits regulating micturition].

PMID- 30101858
TI  - Phenotypic Screening Using Patient-Derived Induced Pluripotent Stem Cells
      Identified Pyr3 as a Candidate Compound for the Treatment of Infantile
      Hypertrophic Cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by
      hypertrophy of the myocardium. Some of the patients are diagnosed for HCM during
      infancy, and the prognosis of infantile HCM is worse than general HCM.
      Nevertheless, pathophysiology of infantile HCM is less investigated and remains
      largely unknown. In the present study, we generated induced pluripotent stem
      cells (iPSCs) from two patients with infantile HCM: one with Noonan syndrome and
      the other with idiopathic HCM. We found that iPSC-derived cardiomyocytes (iPSC
      CMs) from idiopathic HCM patient were significantly larger and showed higher
      diastolic intracellular calcium concentration compared with the iPSC-CMs from
      healthy subject. Unlike iPSC-CMs from the adult/adolescent HCM patient,
      arrhythmia was not observed as a disease-related phenotype in iPSC-CMs from
      idiopathic infantile HCM patient. Phenotypic screening revealed that Pyr3, a
      transient receptor potential channel 3 channel inhibitor, decreased both the cell
      size and diastolic intracellular calcium concentration in iPSC-CMs from both
      Noonan syndrome and idiopathic infantile HCM patients, suggesting that the target
      of Pyr3 may play a role in the pathogenesis of infantile HCM, regardless of the
      etiology. Further research may unveil the possibility of Pyr3 or its derivatives
      in the treatment of infantile HCM.

PMID- 30101857
TI  - A Multiple Biomarker Approach in Patients with Cardiac Sarcoidosis.
AB  - Sarcoidosis is a systemic granulomatous disease including heart (cardiac
      sarcoidosis, CS). It has recently been reported that isolated CS, which
      presenting primarily cardiac symptoms without clinical evidence of sarcoid
      involvement in other organs. Diagnostic and prognostic biomarkers of CS,
      especially in isolated CS, have not yet been established.We studied plasma levels
      of angiotensin-converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R),
      B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) in consecutive 172
      patients with diagnosed sarcoidosis. We compared these markers between non
      cardiac sarcoidosis (non-CS, n = 123, 71.5%) and CS patients (n = 49, 28.5%),
      including non-isolated CS (n = 30, 17.4%) and isolated CS (n = 19, 11.1%). ROC
      analysis revealed that BNP identified CS with AUC of 0.85 (P < 0.01) in
      sarcoidosis patients. In addition, ACE and sIL-2R levels were significantly
      higher in non-isolated CS than in isolated CS (P < 0.05). Furthermore, in the Cox
      proportional hazard analysis, cTnI, but not ACE, IL2R or BNP, was a predictor of
      fatal arrhythmia in sarcoidosis patients (HR 2.418, P = 0.003).Higher ACE and
      sIL2-R are associated with systemic lesions, whereas BNP is a useful marker for
      detecting cardiac involvement in sarcoidosis patients. cTnI is a predictor of
      fatal arrhythmia in CS patients. A multiple biomarker approach supports
      comprehensive management of sarcoidosis.

PMID- 30101859
TI  - Three Novel Mutations in FBN1 and TGFBR2 in Patients with the Syndromic Form of
      Thoracic Aortic Aneurysms and Dissections.
AB  - There are many inherited disorders associated with thoracic aortic aneurysms and
      dissections (TAADs), like Marfan syndrome and Loeys-Dietz syndrome (LDS). The 4
      patients in this study all had TAADs and were initially diagnosed with suspected
      Marfan syndrome. We collected peripheral blood samples from the patients and
      their family members and then attempted to identify the causal mutation using
      different methods including PCR, Sanger sequencing, and next generation
      sequencing. We identified 3 novel heterozygous mutations including 2 splicing
      mutations of FBN1 and 1 missense mutation of TGFBR2 in our patients. Although
      these mutation sites have been reported in the Human Gene Mutation Database, the
      nucleotide changes are different. All novel mutations found in this study were
      confirmed to be absent in 50 unrelated normal individuals of the same ethnic
      background. The RT-PCR results of 2 splicing mutations verified that the
      mutations can lead to the skipping of exons. The RT-qPCR results indicated that
      FBN1 mRNA levels were nearly 50 percent lower in the patients than in normal
      controls, indicating that there is almost no expression of truncated fibrillin-1
      because of the nonsense-mediated mRNA decay (NMD) mechanism. To the best of our
      knowledge, we are the first to report these 3 novel mutations. However, the
      pathogenicity of these mutations still needs further confirmation. Our study has
      confirmed or corrected the clinical diagnosis, and enlarged the mutation spectrum
      of FBN1 and TGFBR2. The results should be helpful for prenatal diagnosis and
      genetic counseling.

PMID- 30101861
TI  - [Selective neuronal cell death in retinal degenerative diseases].
AB  - Retinal degenerative diseases, such as glaucoma and retinitis pigmentosa (RP),
      are the leading causes of blindness in adults. In Japan, glaucoma is a leading
      cause, and RP is third major cause of acquired blindness. Specific types of
      neurons are injured in the patients of glaucoma and RP. Retinal ganglion cells
      (RGC) are specifically degenerated in glaucoma. Excitotoxicity caused by excess
      glutamate in the retinal extracellular space is thought to be one of the
      mechanisms of RGC death induced by glaucoma and retinal central artery occlusion.
      Retinal ischemia-reperfusion, intravitreal NMDA injection, intravitreal NO donor
      injection and knock out of glutamate aspartate transporter, which are used as the
      experimental models of glaucoma, are known to induce RGC death. RGCs are
      vulnerable for excess glutamate and oxidative stress related to NO, and this
      vulnerability may be involved in pathogenesis of glaucomatous optic neuropathy.
      RP, which is characterized by progressive photoreceptor-selective degeneration,
      is caused by mutation of the genes related to the function of photoreceptor and
      retinal pigment epithelium. It has not been thoroughly clarified how the
      mutations induce specific photoreceptor death. Tunicamycin is widely known to
      induce ER stress, and intravitreal tunicamycin cause photoreceptor-specific
      degeneration. Therefore, ER stress may cause photoreceptor-selective degeneration
      in RP.

PMID- 30101862
TI  - [Motor neuron heterogeneity and selective vulnerability in ALS].
AB  - Different and selective vulnerability among motor neuron subtypes are a
      fundamental, but unexplained, feature of amyotrophic lateral sclerosis (ALS):
      fast-fatigable (FF) motor neurons are the most vulnerable, and fast fatigue
      resistant/slow (FR/S) motor neurons are relatively resistant. We identified that
      osteopontin (OPN) can serve as a marker of FR/S motor neurons, whereas matrix
      metalloproteinase-9 (MMP9) is expressed by FF motor neurons in mice. In SOD1G93A
      ALS model mice, as the disease progressed, OPN was secreted and accumulated as
      granular deposits in the extracellular matrix. We also detected OPN/MMP9 co
      expressed motor neurons around the disease onset. These double positive motor
      neurons showed the expression of alphavbeta3 integrin (OPN receptor) and up
      regulation of ER stress markers. We discovered that the double positive motor
      neurons are remodeled FR/S motor neurons, which compensated for FF motor neuron
      degeneration (the first wave of degeneration). Genetic ablation of OPN delayed
      the onset of disease, but later accelerated disease progression. This reflects
      two modes of OPN involvement in the pathogenesis of ALS: cell-autonomous and non
      cell-autonomous effects on motor neuron vulnerability. Our study suggests that
      OPN expressed in FR/S motor neurons is involved in the second wave of motor
      neuron degeneration in ALS, and an OPN-alphavbeta3 integrin-MMP9 axis could be a
      potentially useful therapeutic target for ALS.

PMID- 30101863
TI  - [Cellular mechanisms involved in induction of selective degeneration of orexin
      neurons in the hypothalamus].
AB  - Narcolepsy is a kind of sleep disorder featured by selective loss of orexin
      neurons in the lateral hypothalamus. Several lines of evidence, including
      association with specific HLA haplotypes, gene polymorphism in T cell receptor
      and detection of autoantibodies in a subpopulation of patients, suggest that
      autoimmune responses play an important role in the pathogenesis of this disorder.
      Potential relationship with influenza virus infection has also been a matter of
      interest. However, these events may not be able to explain all cases of
      narcolepsy. Based on the structural features of orexin, in addition to the
      findings on the characteristics of orexin neurons obtained from studies in
      organotypic hypothalamic slice cultures, we proposed novel mechanisms potentially
      involved in selective degeneration of orexin neurons. Increase in local
      production of nitric oxide induced by several life style-related conditions such
      as shortage of sleep and intake of high fat diet leads to inactivation of protein
      disulfide isomerase. Consequently, abnormal aggregates of orexin and/or its
      precursor that possess two intra-molecular disulfide bonds accumulate within
      orexin neurons. In addition to the increase in endoplasmic reticulum stress,
      accumulation of orexin as abnormal aggregates leads to increased excitability of
      orexin neurons by shutdown of feedback inhibition resulting from deficits in
      orexin release. These mechanisms may provide a clue to understand the pathogenic
      mechanisms of various neurological and psychiatric disorders accompanied by a
      decrease of orexin.

PMID- 30101864
TI  - [Signaling and functions of G-protein-coupled receptor 3 in cerebellar granular
      neurons].
AB  - G-protein-coupled receptor 3 (GPR3) is a member of the class A rhodopsin-type
      GPCR family and is highly expressed in various neurons. A unique feature of GPR3
      is its ability to constitutively activate the Galphas protein without the
      addition of ligands, which results in the elevation of the basal level of
      intracellular cAMP. During the development of the cerebellum, GPR3 expression is
      upregulated in cerebellar granular neurons (CGNs) and maintained thereafter. In
      our previous studies, we showed that the intrinsic expression of GPR3 in CGNs is
      highly associated with neurite outgrowth, neurite differentiation, and neuronal
      survival. Recently, we have focused on the possible signaling pathways associated
      with GPR3-mediated neurite outgrowth in CGNs. Interestingly, GPR3-mediated
      neurite outgrowth is mediated by not only PKA-dependent signaling pathways but
      also PI3K-mediated signaling pathways. Moreover, the Gbetagamma-mediated
      signaling pathway is involved in GPR3-mediated neurite outgrowth. These results
      suggested that neural expression of GPR3 stimulates multiple downstream signaling
      pathways, contributing to the maintenance of homeostasis in neurons. Further
      precise analyses of constitutively active GPCRs may help in unveiling novel
      neuronal functions.

PMID- 30101865
TI  - [Functional roles of phosphotyrosine adaptor Shc in the brain].
AB  - Adaptor molecules (adaptor proteins) have indispensable roles in cellular
      signaling, essential for cellular proliferation, development and metabolism. Shc
      (Src homology and collagen homology)-family molecule is a group of adaptor
      molecules, and indicated to be involved in intracellular phosphotyrosine
      signaling. Shc family has 4 subtypes, ShcA-ShcD, and there are long and short
      isoforms in ShcA and ShcC whereas ShcB and ShcD have short isoform only. There
      are three domains conserved in all Shc-family isoforms: phosphotyrosine-binding
      (PTB) domain, collagen-homology 1 (CH1) domain and Src-homology 2 (SH2) domain,
      from the N-terminal to C-terminal. PTB and SH2 domains recognize and bind to
      phosphotyrosine in other molecules, and CH1 domain is recognized and bind to SH2
      domain in Grb2, an adaptor molecule, when the tyrosine residues in the domain are
      phosphorylated. Expression of ShcA is observed in all tissues except for brain in
      adult animals, although ShcA mRNA is detected in brain during embryonic days. On
      the other hand, in adult brain, expressions of ShcB, ShcC, and ShcD are observed.
      Analysis of single knockout mice (ShcA (neuron specific), ShcB, ShcC) and double
      knockout mice for ShcB and C indicated essential roles of Shc-family molecules in
      proliferation and survival of cells in various brain regions as well as synaptic
      plasticity and higher brain functions such as learning and memory. Studies on
      multiple-knockout mice of Shc-family molecules may further clarify possible
      involvements of Shc family in physiological and pathophysiological functions in
      brain.

PMID- 30101866
TI  - [Importance of diacylglycerol signaling in cerebellar motor coordination].
AB  - Brain can be roughly divided into two parts, cerebrum and cerebellum. Cerebrum
      controls higher brain functions including memory, emotion and cognition, while
      cerebellum is important for motor coordination. The only output neuron in
      cerebellum, Purkinje cell, regulates long term depression (LTD). LTD and
      morphology of Purkinje cells are important for motor function. So far, disorder
      of protein kinase C (PKC) alpha and gamma, which are expressed in Purkinje cells,
      impaired LTD, morphology of Purkinje cells and motor coordination. Diacylglycerol
      kinase (DGK) gamma phosphorylates diacylglycerol (DG) and is abundantly expressed
      in Purkinje cells. In other words, DGKgamma can attenuate PKC activity by
      reducing amount of DG and may contribute to motor coordination. However, its
      physiological role has not been elucidated. Therefore, we developed DGKgamma
      knockout (KO) mice and investigated their LTD, morphology of Purkinje cells, and
      cerebellar motor coordination. We found that cerebellar motor coordination and
      LTD were impaired in the DGKgamma KO mice and the morphology of Purkinje cells
      from DGKgamma KO mice was significantly retracted. Interestingly, abnormal
      activation of PKCgamma was involved in impairment of the morphology of Purkinje
      cells from DGKgamma KO mice. These results indicated that DGKgamma was involved
      in cerebellar LTD and morphology of Purkinje cells, and DG signaling is important
      for cerebellar motor coordination.

PMID- 30101867
TI  - [Usage of common marmoset to drug discovery research].
AB  - Rodent laboratory animals, such as mice and rats have been greatly contributing
      to biomedical research. Although its usefulness would not change in the future,
      nonhuman primates (NHPs) also offer excellent models for preclinical research to
      assess safety and efficacy of developing novel therapeutic approaches because of
      their similarities of genetics, metabolism and physiological characteristics to
      humans. Recent years, the gene modification technology in nonhuman primates has
      been developed. In fact, pre-clinical studies using nonhuman primates are
      increasing in the world, especially in the neuroscience research field. Among the
      NHPs, the common marmoset (Callithrix jacchus) is one of a suitable NHP
      laboratory animal for producing genetically modified models because they are
      fecund animal. This article outlines the common marmoset and that of the disease
      models.

PMID- 30101868
TI  - [Current status and future perspective of regenerative medicine for the
      pancreas].

PMID- 30101869
TI  - [Current status and future prospects of pancreas transplantation].

PMID- 30101870
TI  - [Pancreatic islet transplantation:current status and future perspectives].

PMID- 30101871
TI  - [Current status of islet autotransplantation].

PMID- 30101872
TI  - [Current status and future of islet xenotransplantation].

PMID- 30101873
TI  - [Infection status of Helicobacter pylori with antibody values of 3.0U/mL or more
      and less than 10.0U/mL in the LZ test "Eiken" H. pylori antibody].
AB  - The LZ test "Eiken" for H. pylori antibody (LZ test) was examined. In patients
      with an antibody titer of >=3.0U/mL and <10.0U/mL among 698 patients who
      underwent breath tests, the status of H. pylori infection was assessed from the
      results of the 13C urea breath test and the findings of gastric mucosal atrophy
      by performing an upper gastrointestinal endoscopy. A positive 13C urea breath
      test was observed in 22.3% of these patients (156/698, 95% confidence interval
      19.4-25.6%), and gastric mucosal atrophy of C-2 or greater was observed in 39.7%.
      We presumed that 156 (22.3%) patients had present H. pylori infections, 141
      (20.2%) patients had experienced a previous infection, and 401 (57.5%) patients
      were uninfected. The infection rate of H. pylori (current infection+previous
      infection) was treated as a so-called "risk of gastric cancer" and was 42.6%
      (297/698, 95% confidence interval 38.9-46.3%). In the LZ test, the concept of a
      negative high value should be understood. A receiver operating characteristic
      curve plotted depending on whether the 13C urea breath test was positive or not
      gave a positive cutoff value of 5.6U/mL;values greater than the cutoff value were
      taken as indicative of the need to investigate the status of H. pylori infection.
      Even without gastric mucosal atrophy, 2.0% of these patients had a positive
      breath test. For gastritis localized in the antrum (C-1), 17.8% of the patients
      had positive breath test results.

PMID- 30101874
TI  - [Rupture of small intestinal varices diagnosed by CTAP and gastrointestinal
      bleeding scintigraphy and treated by percutaneous phlebosclerozation
      angioembolization].
AB  - A 55-year-old man was admitted to our hospital because of massive
      gastrointestinal bleeding. He had a history of type B liver cirrhosis, multiple
      abdominal surgeries, and endoscopic treatment of esophageal varices. Colonoscopy
      was performed, but the source of bleeding could not be identified. Computed
      tomography during arterial portography (CTAP) demonstrated small intestinal
      varices and collateral veins from the superior mesenteric vein to the epigastric
      vein. We performed phlebosclerozation by directly puncturing the epigastric vein
      under the skin. Remission of bleeding was then attained. No recurrence of
      gastrointestinal hemorrhage has occurred after the phlebosclerozation. We believe
      that CTAP is useful when diagnosing small intestinal varices and that
      percutaneous phlebosclerozation should be considered as a treatment option for
      small intestinal varices.

PMID- 30101875
TI  - [Gastric myxoid epithelioid gastrointestinal stromal tumor harboring PDGFRA gene
      mutation:a case report].
AB  - A 67-year-old man visited our hospital with an enlarging abdominal mass several
      months after he had first noticed his symptoms. An elastic firm tumor was
      palpated on the left side of the abdomen upon physical examination. The blood
      test results were normal. Contrast-enhanced computed tomography of the abdomen
      revealed a 10-cm-diameter homogeneous low-density cystic tumor located at the
      dorsal portion of the gastric corpus. Enhancement of a few net-like structures
      was noted, but most of the lesion was not enhanced. Gastroendoscopy revealed the
      lesion to be a submucosal tumor with a smooth mucosal surface and no ulceration.
      Endoscopic ultrasonography showed the tumor arising from the fourth layer of the
      gastric wall. The tumor was completely resected by laparotomy and partial
      gastrectomy. It was capsulated and contained serous fluid with little solid
      tissue. Histologically, there were sparse tumor cells within the myxoid
      interstitium. Immunostaining results were weakly positive for KIT and CD34
      positive accompanied by mast cell infiltration. A platelet-derived growth factor
      receptor alpha (PDGFRA) exon 18 (D842V) mutation was identified, and the lesion
      was ultimately diagnosed as myxoid epithelioid gastrointestinal stromal tumor
      (GIST) of intermediate- and low-risk according to Fletcher's classification and
      Miettinen's classifications, respectively. GISTs with PDGFRA D842V mutations are
      reportedly resistant to imatinib, and GISTs originating from the stomach are
      reportedly less malignant than others. The patient was observed without adjuvant
      therapy after surgery because of the relatively low risk of metastasis or
      recurrence and the potential risk of imatinib resistance. No recurrence was
      observed for >=5 years after the surgery. We herein report this rare case and
      describe its clinical characteristics.

PMID- 30101876
TI  - [A case of mature intestinal malrotation with cecal volvulus].
AB  - We report an uncommon case of an elderly patient with cecal volvulus caused by
      intestinal malrotation. We performed lower gastrointestinal endoscopy on an 84
      year-old man with a chief complaint of abdominal distention and fever. However,
      emergency surgery had to be performed because intestinal perforation had
      occurred. The patient had cecal volvulus associated with incomplete rotation of
      the intestine. Subsequently, the patient developed multiple organ failure and
      died 2 days after the surgery. Despite its low incidence, we believe that the
      possibility of intestinal malrotation should be considered in elderly patients
      who present with abdominal distention for which the definitive diagnosis cannot
      be easily obtained.

PMID- 30101878
TI  - Flow-based Analytical Techniques.

PMID- 30101877
TI  - [A case of leptomeningeal carcinomatosis involving loss of eyesight after total
      gastrectomy for gastric cancer].
AB  - A 78-year-old woman had undergone total gastrectomy and chemotherapy for gastric
      cancer (pT4N3bM0 Stage IIIC, poorly differentiated adenocarcinoma). She received
      S-1 monotherapy 3 times weekly (S-1 at 80mg twice daily for 14 days, every 3
      weeks). She underwent routine examinations, including tumor markers and computed
      tomography. She had no signs of recurrent disease, but she suffered from a loss
      of eyesight 2 years and 8 months after the operation. A choked disc was found,
      but she had no headaches, nausea, or unconsciousness, which indicated high
      intraventricular pressure. Enhanced T2-weighted magnetic resonance imaging showed
      high intensity around the optic nerve. We performed cerebrospinal fluid
      cytological analysis, which showed poorly differentiated adenocarcinoma. She was
      diagnosed as having leptomeningeal carcinomatosis of gastric cancer. The patient
      chose best supportive care and died 2 months after symptoms appearance.
      Histological analysis during the autopsy showed moderately to poorly
      differentiated adenocarcinoma. The carcinoma had also infiltrated the spinal
      cord, peritoneum, and adrenal glands. Histologically, the carcinoma had
      infiltrated the optic nerve, which caused loss of eyesight. We have not yet
      established effective therapies for leptomeningeal carcinomatosis, and the
      prognosis is poor. Leptomeningeal carcinomatosis of gastric cancer that appears
      by loss of eyesight is very rare. This case illustrates that the possibility of
      leptomeningeal carcinomatosis should be considered when we treat patients with
      loss of eyesight of an unknown cause after surgery.

PMID- 30101880
TI  - Damage-less Handling of Exosomes Using an Ion-depletion Zone in a Microchannel.
AB  - Exosomes are of increasing research interest because they are integral to cell
      cell communication and are implicated in various disease states. Here, we
      investigated the utility of using an ion-depletion zone in a microfluidic device
      to concentrate exosomes from the culture media of four types of cell lines.
      Furthermore, we evaluated the extent of damage to the exosomes following
      concentration by an ion-depletion zone microchannel device compared with exosomes
      concentrated by a conventional ultra-centrifugation technique. Our results
      conclusively demonstrate that significantly less damage is incurred by exosomes
      following passage through and concentration by the ion-depleted zone microchannel
      device compared to concentration by ultra-centrifugation. Our findings will help
      extend the utility of exosomes to various applications.

PMID- 30101879
TI  - Selective Determination of Levodopa in the Presence of Vitamin B6, Theophylline
      and Guaifenesin Using a Glassy Carbon Electrode Modified with a Composite of
      Hematoxylin and Graphene/ZnO.
AB  - An electrode has been developed based on using a composite of
      hematoxylin/graphene/ZnO nanocomposite to modify a glassy carbon electrode (GCE).
      The electrode (HGGCE) was tested and found to be applicable for the voltammetric
      analysis of levodopa in the presence of vitamin B6, theophylline and guaifenesin
      using a 0.1 M phosphate buffer solution (PBS) pH 7 as the solvent. The HGGCE was
      used as the working electrode in cyclic voltammetry (CV) and square wave
      voltammetry (SWV) studies on the electrochemical behavior of levodopa at its
      surface. The results showed a dramatic enhancement in the oxidation current of
      levodopa and a shift in its oxidation potential towards more negative potentials
      as opposed to identical tests using bare GCE as the working electrode. The
      studies showed that the increase in the oxidation current has two linear profiles
      in two concentration ranges of 0.05 - 90.0 and 90.0 - 1000.0 MUM. The detection
      limit of SWV analysis using the modified electrode was determined to be 0.03 MUM
      (S/N = 3). Further advantages of the methods based on HGGCE include the simple
      modification procedure of the electrode, as well as its excellent sensitivity and
      reproducibility. The modified electrode was eventually found to be applicable to
      the determination of mixtures of levodopa, vitamin B6, theophylline and
      guaifenesin in real samples.

PMID- 30101881
TI  - A Label-free Resonance Rayleigh Scattering Sensor for Detection of Thrombin Based
      on Aptamer Recognizing.
AB  - The interaction between thrombin binding aptamer (TBA) and thrombin (TB) was
      studied by resonance Rayleigh scattering (RRS). In neutral medium, TBA is present
      in a balanced form between a G-quadruplex structure and a random coil structure,
      and the TBA can be induced by metal ions to form a G-quadruplex structure. Upon
      addition of thrombin, the G-quadruplex selectively bound to TB, which resulted in
      enhanced resonance Rayleigh scattering. The scattering intensities increased
      proportionally with the concentration of TB from 10 to 50 nM. The method had very
      high sensitivity and good selectivity, and the detection limit (3delta/s) was 1
      nM. In this work, the spectral characteristics of RRS, the optimum conditions of
      the reaction, and influencing factors for the RRS intensities were investigated.
      Furthermore, the structure of the TBA-TB complex and the sensing mechanism were
      explored. The TB sensor was applied to a diluted human serum sample with
      satisfactory results, indicating the potential of this method to be applied to
      biological samples. A selective and simple RRS sensor for the detection of trace
      amounts of TB is proposed based on conformational change of TBA.

PMID- 30101882
TI  - Separation and Analysis of Sucrose Esters in Tobacco by Online Liquid
      Chromatography-Gas Chromatography/Mass Spectrometry.
AB  - In this work, a strategy of in-series combination of ultrasound-assisted
      extraction and online LC-GC/MS was constructed for effective separation and
      analysis of sucrose esters in tobacco. Sucrose esters were first extracted by
      ultrasound-assisted extraction with high efficiency and easyhandling. Online LC
      GC/MS was then applied for sucrose ester clean-up and analysis. To better
      evaluate the effectiveness of this strategy, we limited our focus to five groups
      of sucrose ester isomers. Each group differed in mass from the next by 14 Da. The
      obtained coefficient of the calibration curve was 0.9986. Limit of detection
      (LOD) and limit of quantitation (LOQ) were 0.05 and 0.16 MUg/ mL, respectively.
      The recovery was above 90% and the reproducibility was below 4%. This strategy
      was subsequently applied to the comparison of relative amounts of five groups of
      sucrose esters extracted from three different parts of aromatic tobacco. The
      satisfactory performance indicated that this strategy has great prospect for the
      rapid and high-throughput analysis of sucrose esters in tobacco.

PMID- 30101883
TI  - A Dual Functional Cardiomyocyte-based Hybrid-biosensor for the Detection of
      Diarrhetic Shellfish Poisoning and Paralytic Shellfish Poisoning Toxins.
AB  - Okadaic acid (OA) and saxitoxin (STX) are typical toxins of diarrhetic shellfish
      poisoning (DSP) and paralytic shellfish poisoning (PSP), respectively, which are
      highly toxic marine toxins threatening human health and environmental safety. OA
      is a potent inhibitor of serine/threonine protein phosphatases that can cause
      cellular death, while STX is an inhibitor of sodium channel that can lead to
      neurological damage. In this work, a dual functional cardiomyocyte-based
      biosensor was proposed to detect DSP and PSP toxins by monitoring the viability
      and electrophysiology of cardiomyocytes. The results showed that the viability of
      cardiomyocytes was sensitive to the OA and STX, resulting in significant changes
      of the electrophysiological properties, including amplitude, firing rate and
      duration of the extracellular field potential (EFP). The detection limits of the
      hybrid-biosensor are as low as 7.16 ng/mL for OA and 5.19 ng/mL for STX. In
      summary, all of the results indicate that the dual functional cardiomyocyte-based
      hybrid-biosensor will be a promising and utility tool for shellfish toxin
      detection.

PMID- 30101884
TI  - Evaluation of Type-A Endonucleases for the Quantitative Analysis of DNA Damage
      due to Exposure to Acetaldehyde Using Capillary Electrophoresis.
AB  - The substrate selectivities of three endonucleases were studied quantitatively
      using capillary zone electrophoresis to find one giving N2-ethyl(Et)-2'
      deoxyguanosine-5'-monophosphate (5'-dGMP) and cyclic 1,N2-propano(CPr)-5'-dGMP
      from DNAs damaged by acetaldehyde (AA). Six 2'-deoxyribonucleoside-5'
      monophosphates to be quantified in the hydrolysis solutions of DNAs, namely, Et
      5'-dGMP, CPr-5'-dGMP, and four authentic ones, were completely separated using a
      100 mM borate running buffer solution having an optimized pH of 9.67. Using the
      present method, nuclease reactions of nuclease S1 (NS1), nuclease P1 (NP1), and
      nuclease Bal 31 to 2'-deoxyribonucleoside-5'-monophosphates from damaged Calf
      thymus (CT-) DNAs were monitored. The CT-DNAs were prepared by treatment with AA
      to generate Et-guanine or CPr-guanine internally. Bal 31 hydrolyzed the damaged
      CT-DNAs to yield Et-5'-dGMP and CPr-5'-dGMP quantitatively. The two 5'-dGMP
      adducts were not detected in the hydrolysis solutions using NS1 or NP1. Bal 31
      can be a suitable nuclease for analyzing DNA damages caused by AA.

PMID- 30101885
TI  - A Rapid Enrichment Technique for the Ultratrace Determination of Nickel in Water
      Samples Using a Nanofiber-composite Membrane Filter.
AB  - A new method for the rapid enrichment and highly sensitive determination of
      nickel ion has been developed by using a nanofiber-composite membrane filter,
      which was fabricated by stacking a nanofibrous material made of nylon 6 over a
      water-permeable membrane filter. The noncharged nickel-alpha-furil dioxime
      complex was adsorbed on a nanofibrous layer of the membrane filter under
      significantly higher flow rates than those used for conventional solid-phase
      extraction techniques. Highly sensitive determinations with detection limits at
      sub-parts per billion levels were achieved by enrichment from 50 mL of the
      complex solution, and the enrichment was completed within 3 min. The color that
      was developed on the membrane filter was successfully subjected to visual
      colorimetric analysis and quantitative determination by solid-phase
      spectrophotometry. In addition, colorimetric determination was feasible with a
      handheld spectrometer after elution of the colored agent with 50 MUL of acetone.
      This combination of rapid enrichment and spectrometric measurement in a small
      volume sample provides a useful analytical method suitable for on-site analysis,
      which requires neither expensive instruments nor high laboratory skills.

PMID- 30101886
TI  - Amperometric Determination of Hydrogen Peroxide in Whitening Gels Using Boron
      doped Diamond Electrode.
AB  - The aim of this work was to develop an electrochemical cell and a methodology
      based on an amperometric determination of hydrogen peroxide in whitening gel
      samples under a boron-doped diamond electrode using flow injection analysis.
      Different parameters were evaluated to obtain the best conditions of analysis:
      among them, the flow of electrolyte at 2.8 mL min-1, the loop sampling 175 MUL
      (28.5 cm), an analytical length of 159 MUL (25 cm) and an applied potential of
      +0.60 V vs. Ag/AgCl(sat). The proposed method was suitable in terms of precision
      of results (RSD <10%); the accuracy was confirmed in the analysis of the gels
      through addition and recovery studies with results between 74 and 107%. The
      method was then applied to the analysis of tooth-whitening gel samples, acquired
      in different cities of the region. Regarding the results, a medium concentration
      value of 2.39% (w/w) was observed.

PMID- 30101887
TI  - A Robust Method for the Determination of Cr(VI) and Cr(III) in Industrial
      Wastewaters by Liquid Chromatography-Inductively Coupled Plasma Mass Spectrometry
      Combined with a Chelating Pretreatment with 2,6-Pyridinedicarboxylic Acid.
AB  - We have developed a method for the determination of Cr(VI) and Cr(III) in
      industrial wastewater by liquid chromatography-inductively coupled plasma mass
      spectrometry (LC-ICP-MS) combined with a chelating pretreatment with 2,6
      pyridinedicarboxylic acid (PDCA). The PDCA unified the chemical forms of the
      Cr(III) species in water samples by the formation of a stable Cr(III)-PDCA
      complex, which was then separated by a LC column. The chromatographic mobile
      phase at neutral pH and the column of a mixed-bed of anion and cation exchangers
      successfully separated not only the chromium species without any redox
      conversion, but also chloride, which interfered with ICP-MS detection. The method
      detection limits measured at m/z 53 were 0.66 MUg of Cr L-1 for Cr(III) and 0.74
      MUg L-1 for Cr(VI) with a sample injection volume of 20 MUL under a no gas mode.
      The recoveries of spiked Cr(VI) at 50 and 500 g L-1 into the fifteen kinds of
      industrial wastewater samples were satisfactory (>90%). The proposed method for
      the determination of Cr(VI) was also validated by comparing with a colorimetric
      method using 1,5-diphenylcarbazide prescribed by the ISO 11083 and the JIS K0102.

PMID- 30101888
TI  - Umbelliferone as a Small Molecular Peroxidase Mimic towards Sensitive Detection
      of H2O2 and Glucose.
AB  - In this work, umbelliferone, a kind of coumarin derivative, was proved to exhibit
      peroxidase-like activity that could catalyze the oxidation of 3,3',5,5'
      tetramethylbenzidine (TMB) in the presence of hydrogen peroxide to generate a
      blue-colored oxide (oxTMB). The catalytic mechanism is similar to that of native
      enzymes (e.g. horseradish peroxidase, HRP) and nanozymes, which follow the
      Michaelis-Menten kinetics behavior. Meanwhile, the 7-hydroxyl group of
      umbelliferone plays a significant role in the peroxidase-like activity. Compared
      with enzymes and nanozymes, this small molecular mimic enzyme possesses the
      advantages of low cost, simple molecular structures, small molecular weight and
      high stability against harsh conditions. Based on the favorable peroxidase
      mimetic activity of umbelliferone, a convenient, practical and sensitive H2O2 and
      glucose detection method was successfully established. This work not only opens
      some new inspirations into seeking for novel molecular enzyme mimetics with
      excellent catalytic activities, but also provides promising assays for clinical
      diagnosis.

PMID- 30101889
TI  - Ion-Transfer Voltammetry at a Water/1,2-Dichloroethane Interface Using
      Photoionization by Ultraviolet Irradiation: Detection of Cation Radicals of p
      Phenylenediamine Derivatives.
AB  - We have attempted to detect electrically neutral substances by ion-transfer
      voltammetry at an interface between two immiscible electrolyte solutions (ITIES),
      such as an interface between water and 1,2-dichloroethane (a W/DCE interface), by
      irradiating the interface with ultraviolet light (200 - 300 nm). In the present
      work, while considering the facts that p-phenylenediamine derivatives are soluble
      in DCE, but insoluble in water, and that cation radicals of the derivatives are
      fairly stable in various media, we photoionized the derivatives in a DCE phase by
      ultraviolet irradiation, and after that carried out ion-transfer voltammetry at a
      W/DCE interface. As a result, we could successfully observe ion-transfer waves of
      cation radicals of the derivatives from the W to DCE phase. Namely, the cation
      radicals are generated in the DCE phase by ultraviolet irradiation, and
      subsequently distributed into the W phase. In addition to these ion-transfer
      waves, we also found that facilitated proton-transfer waves by the derivatives
      were shifted to a more negative potential region after ultraviolet irradiation,
      because of hydrogen chloride formed from photodecomposition of DCE by ultraviolet
      irradiation.

PMID- 30101890
TI  - Effect of epsilon-Poly-L-lysine on a Glucose Sensor Based on Glucose Oxidase and
      Ferricyanide Ion.
AB  - epsilon-Poly-L-lysine (epsilonPL) is a homopolymer of L-lysine residues with
      linkages between the alpha-carboxyl and epsilon-amino groups. epsilonPL exists as
      a polycationic species under acidic and neutral conditions, and can form a
      polyion complex with negatively charged glucose oxidase (GOx). We previously
      reported that epsilonPL significantly promoted a GOx enzymatic reaction using
      ferricyanide ion ([Fe(CN)6]3-) as the oxidant. Here, we construct a GOx
      immobilized electrode using epsilonPL and glutaraldehyde, and show that
      [Fe(CN)6]3- can efficiently act as the mediator in this electrode. Ferricyanide
      ion failed to function adequately as the mediator when bovine serum albumin or
      other polyamines (e.g., polyallylamine, alpha-poly-L-lysine) were used instead of
      epsilonPL. The GOx-immobilized electrode using epsilonPL successfully responded
      to glucose even when the [Fe(CN)6]3- concentration was as low as 1 mM, and
      exhibited a wide dynamic range of up to several tens of mM. Thus, epsilonPL is
      considered to be a useful additive for glucose sensors based on the [Fe(CN)6]4-/3
      -mediated GOx catalytic current.

PMID- 30101891
TI  - Phase Separation Multi-phase Flow Using an Aqueous Two-phase System of a
      Polyethylene Glycol/Dextran Mixed Solution.
AB  - Polyethylene glycol/dextran mixed solution as an aqueous two-phase system was fed
      into a fused-silica capillary tube under different conditions, resulting in phase
      transformation leading to phase separation multi-phase flow through/along a
      liquid-liquid interface. As one flow-type example, when 6.4 wt% polyethylene
      glycol and 9.7 wt% dextran aqueous solution containing 1.0 mM Rhodamine B was fed
      into the capillary tube at 3 degrees C, tube radial distribution flow (annual
      flow) was observed through bright-field microscopy. Tube radial distribution flow
      consisted of a dextran-rich inner phase and polyethylene glycol-rich outer phase.
      We also examined the distribution of proteins, such as bovine serum albumin,
      hemoglobin, and lysozyme, in the inner and outer phases through use of double
      capillary tubes with different inner diameters. The protein distribution was
      greater in the inner (dextran-rich) phase than the outer (polyethylene glycol
      rich) phase. The distribution ratios of the three proteins (ratio of the
      inner/outer protein concentration) were 2.3, 4.2, and 1.8, respectively. The
      proteins concentrated in the dextran-rich phase through tube radial distribution
      flow of a polyethylene glycol/dextran mixed solution.

PMID- 30101893
TI  - Measuring Number of Free Radicals and Evaluating the Purity of Di(phenyl)-(2,4,6
      trinitrophenyl)iminoazanium [DPPH] Reagents by Effective Magnetic Moment Method.
AB  - Di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium [DPPH] is widely used as a standard
      for measuring the number of free radicals. Here, we evaluated the number of free
      radicals of "DPPH" reagents from three manufacturers by effective magnetic moment
      method. Interestingly, the reagents from different manufacturers had varying
      temperature dependencies for both magnetic moment and g-value at low
      temperatures. As a result, the maximum relative difference among the three
      reagents on the number of free radicals per unit mass was 20%. Carbon hydrogen
      nitrogen (CHN) analyses, high-resolution EPR measurements, FT-IR measurement, and
      NMR measurement confirmed that a major component of only one among the three
      reagents was "pure" DPPH. The evaluated purity based on free radical content was
      0.998 kg kg-1 with expanded uncertainty of 0.036 kg kg-1. The other two reagents
      were found to be contaminated by several % of benzene in the DPPH crystal
      structure.

PMID- 30101892
TI  - Fluorescence-based Polymerase Amplification for the Sensitive Detection of DNA
      Methyltransferase Activity.
AB  - DNA methyltransferase (MTase) is related to transcriptional repressor activity in
      biological functions. It is an essential for cancer diagnosis and therapeutics to
      detect DNA MTase activity sensitively. Here, a fluorescent system based on
      polymerase amplification has been developed to detect DNA adenine MTase (Dam)
      activity sensitively. The amplification is triggered by the probe DNA regions a,
      which are the primes of a polymerase-induced replicated reaction. They come from
      methylation and a digestion reaction of DNA S1-S1, including a 5'-GATC-3'
      sequence recognized by Dam MTase and methylation sensitive restriction
      endonuclease Dpn I. The intensities of fluorescence are dependent on the Dam
      MTase activity. The method shows fine sensitivity with a detection limit of 3.2 *
      10-4 U mL-1 and specificity for Dam MTase. In human serum samples, the method has
      been successfully applied, and it has also been used to screen the inhibitors,
      which means that the developed method can be a powerful and potential tool for
      drug development and clinical diagnosis in the future.

PMID- 30101895
TI  - Enzyme immunoassays for water-soluble steroid metabolites in the urine and feces
      of Japanese macaques (Macaca fuscata) using a simple elution method.
AB  - Keiko SHIMIZU and Keiko MOURI Vol. 80, No. 7 (2018), p. 1139, the number of the
      Plate preparation section should have been as follows:I ErrorI Plate preparation.
      Anti-rabbit IgG (H+L) goat serum (Rockland Immunochemicals Inc., Limerick, PA,
      U.S.A.) was diluted to 0.15 MUg/ml in pH 9.6, 0.05 M carbonate buffer, and 50 MUl
      was added to microtiter plates (Maxisorp flat-bottom, Thermo Fisher Scientific,
      Waltham, MA, U.S.A.) for the E1C, PdG and E3G assays.II CorrectionI Plate
      preparation. Anti-rabbit IgG (H+L) goat serum (Rockland Immunochemicals Inc.,
      Limerick, PA, U.S.A.) was diluted to 15 MUg/ml in pH 9.6, 0.05 M carbonate
      buffer, and 50 MUl was added to microtiter plates (Maxisorp flat-bottom, Thermo
      Fisher Scientific, Waltham, MA, U.S.A.) for the E1C, PdG and E3G assays.

PMID- 30101896
TI  - Durations of first and second periods of depression-induced sick leave among
      Japanese employees: the Japan sickness absence and return to work (J-SAR) study.
AB  - This study aimed to clarify the difference between the durations of first and
      second periods of depression-induced sick leave and to identify predictors of a
      prolonged second period of depression-induced sick leave. Among Japanese
      employees who were registered in the Japan sickness absence and return to work (J
      SAR) study, the subjects were those employees who returned to work after an
      initial period of depression-induced sick leave (F3; ICD-10, based on a
      psychiatrist's certificate), and returned to work after a second period of
      depression-induced sick leave. The subjects' second periods of sick leave (mean:
      156.9 days) were longer than their first periods of sick leave (107.3 d)
      (Wilcoxon test, p=0.007). In the logistic regression analysis (Table 2), "longer
      duration of the first period of sick leave" (Odds ratio: 3.258, 95%CI: 1.780
      5.963, p<0.001) was identified as a significant predictor of a longer recurrent
      period of sick leave. Individuals who experience a long initial period of
      depression-induced sick leave should be supported carefully by occupational
      health professionals after they RTW.

PMID- 30101897
TI  - What causes patients with breast cancer to change employment?: evidence from the
      health insurance data in a medical facility.
AB  - This study aims to make clear the following aspects of breast cancer patients and
      their occupation. 1. What percentage of patients have changed their working
      status around surgery? 2. When did patients change their employment? 3. What is
      the cause of the employment change? We investigated 269 patients who underwent
      curative surgery for primary breast cancer at one university hospital in Tokyo.
      Patients who were under the age of 58 at the time of surgery and had the
      experience of being a company or government employee during a year prior to the
      surgery were used as sample for analysis. To determine factors related to the
      employment change, multiple logistic regression analysis was performed. 19%
      patients changed the employment status before and after surgery. Of those, 19%
      changed the employment by the end of surgery month while 42% did by the fourth
      month after surgery. Treatment-related factors such as mastectomy and the
      combination of chemotherapy and hormone therapy affected changes in employment.
      We believe that the validity of our study can be confirmed by comparing with the
      previous study results. We show the potential large effects of cancer treatment
      on patients' daily lives.

PMID- 30101898
TI  - Work-to-family conflict rather than family-to-work conflict is more strongly
      associated with sleep disorders in Upper Egypt.
AB  - An important factor for which work and family compete is time. Due to lack of
      evidence, I investigated the associations between work-family conflict (assessed
      by the National Study of Midlife Development in the US) and sleep disorders
      (assessed by the Jenkins Sleep Questionnaire) in a cross-sectional study included
      1,021 Egyptians aged 18-59 years. Both work-to-family (WFC) and family-to-work
      (FWC) were associated with reduced sleep quantity. Moreover, high WFC was
      associated with sleep disorders; the multivariable ORs (95% CIs) were 2.32 (1.63
      3.30) in high versus low WFC, 1.09 (0.79-1.49) in high versus low FWC and 2.41
      (1.52-3.83) in high both WFC and FWC versus low both WFC and FWC. Waking up too
      early with inability to fall asleep again and waking up tired after the usual
      amount of sleep were the most common sleep disturbances with high WFC; while
      insignificant increased risks for waking up several times per night and waking up
      tired after the usual amount of sleep were observed with high FWC. The study
      findings suggest the need for occupational and social health promotion programs
      to help men and women in labor force reach a balanced interaction between work
      and family life in order to reduce sleep complaints.

PMID- 30101899
TI  - Does dispositional optimism moderate the relationship between role conflict and
      risk of disability retirement?
AB  - This study determines whether dispositional optimism moderates the relationship
      between role conflict and the risk of disability retirement. The study was based
      on a combination of self-report survey questionnaire data on role conflict and
      dispositional optimism with official register data on disability benefits from
      the Norwegian Labour and Welfare Administration. The sample comprised 14,501
      Norwegian employees from various occupations and industries. Role conflict was
      significantly related to higher risk (HR 1.35, 95% CI 1.19-1.53), whereas
      optimism was associated with decreased risk (HR 0.75, 95% CI 0.64-0.88), of
      disability retirement. Optimism did not modify the effect on role conflict on
      disability retirement. Having an optimistic life orientation decreases the risk
      of disability retirement in general, but does not protect against the detrimental
      effects of role conflict at the workplace. As optimism is a malleable personality
      characteristic, organizations may benefit from interventions that help employees
      experience daily events more positively.

PMID- 30101900
TI  - Thoracic Paravertebral Extramedullary Hematopoiesis.

PMID- 30101901
TI  - Neurilemmoma Mimicking a Multilocular Cystic Lesion of the Liver.
AB  - Neurilemmomas are benign tumors arising from the sheaths of peripheral nerves.
      They appear rarely in the abdominal cavity. We herein report an 80-year-old man
      with a multilocular cystic neurilemmoma mimicking a liver lesion. Preoperative
      images showed a lesion in the porta hepatis. Although a preoperative diagnosis
      was difficult, surgery was undertaken because of the possibility of malignancy.
      Histologically, the tumor consisted of spindle-shaped cells with positivity for S
      100 protein. The final diagnosis was a neurilemmoma. Porta hepatic neurilemmomas
      are rare. When we encounter a multilocular cystic lesion of the liver,
      neurilemmoma should be considered in the differential diagnosis.

PMID- 30101902
TI  - Substantial Improvement in a Nerve Conduction Study of Lymphoma-associated
      Demyelinating Neuropathy Treated by Intravenous Immunoglobulin and Chemotherapy.
AB  - A 64-year-old woman with lymphoma-associated demyelinating neuropathy was treated
      by 6 cycles of R-CHOP with intravenous immunoglobulin in the first 2 cycles. We
      noted substantial improvement in the findings of a nerve conduction study (NCS)
      after the first cycle, followed by more protracted improvement during the second
      to sixth cycles. The improvement of the neurological symptoms paralleled the
      findings of the NCS. Our case provides important information for understanding
      the etiology and optimization of treatments for lymphoma-associated demyelinating
      neuropathy.

PMID- 30101903
TI  - Pancreatic Acinar Cell Carcinoma with Multiple Liver Metastases Effectively
      Treated by S-1 Chemotherapy.
AB  - A 79-year-old woman was referred for pancreatic tail cancer with multiple liver
      metastases. The pancreatic tail tumor was diagnosed as acinar cell carcinoma
      (ACC) histologically by endoscopic ultrasound-guided fine-needle aspiration.
      Because of multiple liver metastases, S-1 chemotherapy was administered,
      resulting in a partial response to chemotherapy one year later. After
      approximately three years, liver atrophy and esophageal varices developed. We
      suspected S-1 as the cause of the liver cirrhosis. S-1 cessation minimized
      ascites and improved the esophageal varices. Although S-1 can potentially treat
      ACC, we should be watchful for liver cirrhosis caused by its long-term
      administration.

PMID- 30101904
TI  - Resection for Primary Retroperitoneal Serous Adenocarcinoma and Liver Metastasis.
AB  - Primary retroperitoneal serous adenocarcinoma (PRSA) is a rare malignancy of
      which only seven cases have been reported in the literature. The clinical
      features and outcomes of PRSA are not well understood. We herein report a case of
      PRSA with liver metastasis in a 74-year-old woman who was treated with surgical
      excision. The tumor cells were positive for estrogen receptor, Wilms tumor 1,
      PAX8, p53, and cytokeratin AE1/AE3. The final diagnosis was PRSA and liver
      metastasis. The pathological features of PRSA resemble those of ovarian serous
      carcinoma, which suggests that a combination of surgical excision with adjuvant
      chemotherapy may be the best option.

PMID- 30101905
TI  - Reversible Non-parkinsonian Bradykinesia with Impaired Frontal Lobe Function as
      the Predominant Manifestation of Adrenal Insufficiency.
AB  - A 69-year-old Japanese man with a history of suprasellar surgery and irradiation
      developed bradykinesia and mild fatigue without muscle weakness, myalgia,
      pyramidal or extrapyramidal signs, parkinsonian symptoms, or ataxia. An
      endocrinological work-up revealed anterior hypopituitarism associated with
      secondary adrenal insufficiency. Higher brain function tests indicated an
      impaired frontal lobe function. The patient's bradykinesia, fatigue, and frontal
      lobe dysfunction improved within 2 weeks after the initiation of corticosteroid
      replacement therapy. To our knowledge, this is the first reported case of adrenal
      insufficiency manifesting as non-parkinsonian bradykinesia. Physicians should
      consider reversible non-parkinsonian bradykinesia associated with frontal lobe
      dysfunction as an unusual manifestation of adrenal insufficiency.

PMID- 30101906
TI  - A Mass Filling the Right Atrium: A Case of Primary Cardiac Rhabdomyosarcoma.
AB  - A 43-year-old woman presented with worsening shortness of breath and lower
      extremity edema. Echocardiography and computed tomography showed obstruction of
      blood flow due to a mass filling the right atrium. Emergency surgery was
      performed for circulatory failure. Primary cardiac rhabdomyosarcoma was diagnosed
      based on a histological examination. The patient died about two months after the
      diagnosis despite surgical excision and radiation therapy. The poor prognosis may
      have resulted from the grossly incomplete removal of the tumor and chemotherapy
      intolerance. We herein report a case of primary cardiac rhabdomyosarcoma filling
      the right atrium and offer possible reasons for the poor prognosis.

PMID- 30101907
TI  - Elevated Levels of Intelectin-1, a Pathogen-binding Lectin, in the BAL Fluid of
      Patients with Chronic Eosinophilic Pneumonia and Hypersensitivity Pneumonitis.
AB  - Objective Human intelectin-1 (hITLN-1) binds to galactofuranosyl residues, which
      are present in the microbial cell wall, but which are absent in mammalian
      tissues, and has been suggested to play an immunological role against
      microorganisms. However, the involvement of hITLN-1 in the pathogenesis of
      diffuse pulmonary diseases remains unknown. The aim of this study was to compare
      the hITLN-1 concentrations in the bronchoalveolar lavage (BAL) fluid of patients
      with diffuse pulmonary diseases. Methods The cell components and concentrations
      of hITLN-1 were analyzed in the bronchoalveolar lavage (BAL) fluid of 8 patients
      with idiopathic chronic eosinophilic pneumonia (ICEP), 3 patients with drug
      induced eosinophilic pneumonia (drug-EP), 4 patients with hypersensitivity
      pneumonitis (HP), 11 patients with sarcoidosis, 9 patients with cryptogenic
      organizing pneumonia (COP), and 5 patients with idiopathic fibrosing interstitial
      pneumonia (fibrosing nonspecific interstitial pneumonia [fNSIP] or usual
      interstitial pneumonia [UIP]) Results The hITLN-1 concentrations in the BAL fluid
      of patients with ICEP and HP were higher than in those with other diseases. In
      the ICEP group, no significant difference was observed in the hITLN-1
      concentrations of patients with or without a history of bronchial asthma.
      Conclusions The results of the present study suggest that hITLN-1 may be involved
      in the pathogenesis of ICEP and HP, and that an increase in the hITLN-1
      concentration in the BAL fluid may represent a new biomarker for these diseases.

PMID- 30101908
TI  - Anticentromere Antibody-positive Scleroderma Renal Crisis Requiring Dialysis.
AB  - A 70-year-old man with prior Raynaud's phenomena developed hypertension and renal
      insufficiency. Raynaud's phenomena, finger skin thickening, interstitial lung
      disease, and positive anticentromere antibody findings indicated systemic
      sclerosis (SSc). Based on the presence of SSc, severe hypertension with rapidly
      progressive renal failure, and proliferative and obliterative arteriolar
      vasculopathy, scleroderma renal crisis (SRC) was diagnosed. Despite good blood
      pressure control with antihypertensive drugs, hemodialysis was initiated and
      could not be withdrawn owing to unimproved renal dysfunction. Although SRC in
      anticentromere antibody-positive limited cutaneous SSc is extremely rare, some
      patients may develop SRC, and their renal prognosis may be poor.

PMID- 30101909
TI  - Influence of Adherence to Inhaled Corticosteroids and Inhaler Handling Errors on
      Asthma Control in a Japanese Population.
AB  - Objective High adherence to medications and accurate handling of inhaler devices
      are important for asthma management. However, few reports to date have
      simultaneously evaluated adherence and handling errors. We therefore investigated
      the adherence to inhaled corticosteroid (ICS) and inhaler handling errors in the
      same patients in cooperation with pharmacists. Methods Data were derived from a
      survey of physicians and pharmacists treating asthma patients who visited
      participating hospitals and pharmacies from July 2012 to January 2013. The
      patients were evaluated for asthma control using the Asthma Control Test (ACT)
      and for inhaler handling errors using checklists. ICS adherence was evaluated
      based on pharmaceutical records. Results Adherence among participants (n=290) was
      33.3% (mean), and the percentage of inhaler handling errors was 20.0% (mean).
      Total inhalation times in the high-adherence group were fewer than those in the
      low-adherence group. In a comparison by device, adherence to pressurized metered
      dose inhalers was significantly lower than that to Diskus(r) inhalers, presumably
      attributable to the total number of inhalations per day. Adherence, handling
      errors, and total number of inhalations per day were significantly different
      between the asthma-controlled group and the uncontrolled group. A multivariate
      analysis showed that adherence and handling errors were independent factors
      contributing to asthma control. Conclusion Our data indicated that both adherence
      to ICS and device handling errors contributed to asthma control in this
      population.

PMID- 30101910
TI  - The Prognostic Impact of Dose-attenuated R-CHOP Therapy for Elderly Patients with
      Diffuse Large B-cell Lymphoma.
AB  - Objective Although R-CHOP (rituximab, cyclophosphamide, vincristine, doxorubicin,
      and prednisone) is a standard therapy for diffuse large B-cell lymphoma (DLBCL),
      the optimal dose for elderly patients remains unclear. Methods and Patients We
      retrospectively verified our R-CHOP dose-attenuation system implemented from 2005
      for DLBCL patients. Among the 115 DLBCL patients treated during 2001-2010, 33
      patients treated during 2001-2005 received R-CHOP doses adjusted according to
      physicians' decisions (PHY group). Eighty-two patients treated after 2005
      received adjusted R-CHOP doses according to a unified dose-attenuation system
      (UNI group). Patients aged <60, 60-69, 70-79, and >=80 years received the
      standard R-CHOP, 100% R-CHO+P (50 mg/m2), 100% R+75% CHO+P (40 mg/m2), and 100%
      R+50% CHO+P (30 mg/m2), respectively. We compared the responses, survival, and
      treatment cessation between the PHY and UNI groups. Results The patients'
      characteristics between both groups were closely comparable. All PHY patients
      received randomly adjusted R-CHOP doses; 94% of UNI patients received scheduled
      doses. The complete response rates differed significantly between the UNI (77%)
      and PHY patients (50%) (p=0.011). The two-year event-free survival rates were 50%
      and 32% in the UNI and PHY groups, respectively (p=0.0083). The two-year OS rates
      were 77% and 72% in the UNI and PHY group (p=0.16). Among the patients aged >70
      years (n=59) overall survival was shorter in the PHY group (62%) than in the UNI
      group (72%; p=0.02). The UNI group received higher anti-tumor agent doses than
      the PHY group. The therapy discontinuation rates were 5% in the UNI group and 24%
      in the PHY group. Conclusion Carrying out unified dose reduction may improve the
      efficacy and prognosis among elderly DLBCL patients.

PMID- 30101911
TI  - An EGFR-mutated Lung Adenocarcinoma Undergoing Squamous Cell Carcinoma
      Transformation Exhibited a Durable Response to Afatinib.
AB  - Squamous cell carcinoma (SCC) transformation has been identified as a mechanism
      of resistance to first-generation epidermal growth factor receptor tyrosine
      kinase inhibitors (EGFR-TKIs), gefitinib or erlotinib, in EGFR-mutated lung
      cancer. However, whether second- or third-generation TKIs can overcome resistance
      due to SCC transformation remains unclear. We herein report an EGFR-mutated lung
      adenocarcinoma undergoing transformation into SCC that exhibited a durable
      response to afatinib, which is a second-generation irreversible EGFR-TKI. We
      suggest that afatinib can be considered as a treatment option for EGFR-mutated
      tumor undergoing SCC transformation, particularly in the absence of a T790M
      mutation.

PMID- 30101912
TI  - Glutamic Acid Decarboxylase Autoantibody-negative Slowly Progressive Type 1
      Diabetes Mellitus: A Case Report and Literature Review.
AB  - A 59-year-old non-obese Japanese woman developed diabetes mellitus with a
      negative glutamic acid decarboxylase autoantibody (GADA) test result. Her
      hyperglycemia was initially well controlled by oral hypoglycemic agents; however,
      despite continued treatment the hyperglycemia gradually worsened. As she had
      endogenous insulin deficiency and tested positive for insulin autoantibody (IAA),
      insulin therapy was initiated. Few studies have investigated GADA-negative
      patients with slowly progressive type 1 diabetes mellitus (SPT1D). Our IAA
      positive SPT1D patient progressed from the clinical onset of diabetes mellitus to
      starting insulin therapy relatively quickly (1.5 years), similarly to other
      previously reported non-obese patients with GADA-positive SPT1D.

PMID- 30101914
TI  - Hemorrhagic Pericardial Cyst Complicated with Constrictive Pericarditis: A Case
      Report.
AB  - Pericardial cysts are rare abnormalities and are usually asymptomatic. Although
      several case reports on their diagnosis and treatment have been published, those
      on hemorrhagic pericardial cysts remain limited. We herein report the case of a
      70-year-old man with a hemorrhagic pericardial cyst complicated with constrictive
      pericarditis 2 years after the initial diagnosis.

PMID- 30101913
TI  - Lenalidomide as a Beneficial Treatment Option for Renal Impairment Caused by
      Light Chain Deposition Disease: A Case Series.
AB  - Light chain deposition disease (LCDD) is a rare systemic disorder caused by the
      deposition of light chain immunoglobulins, which often results in renal
      impairment associated with either nephrotic syndrome or asymptomatic proteinuria.
      B-cell neoplasms, such as multiple myeloma and lymphoproliferative disorders, are
      well-known underlying diseases in LCDD. Some chemotherapy regimens have been
      reported, but both evidence-based treatment and management for LCDD have yet to
      be established. We herein report three cases of LCDD treated with lenalidomide
      based therapy, resulting in hematologic responses accompanied by a significant
      reduction in proteinuria and improvement in the renal function. We recommend
      lenalidomide-based therapy for renal impairment caused by LCDD.

PMID- 30101916
TI  - Neurolymphomatosis in the Cauda Equina Diagnosed by an Open Biopsy.
AB  - Neurolymphomatosis is a rare form of extranodal malignant lymphoma defined as the
      infiltration of malignant lymphocytes into the central or peripheral nerve. We
      herein report a case of neurolymphomatosis in the cauda equina diagnosed by an
      open surgical biopsy. He presented with muscle weakness, atrophy, numbness and
      hypoesthesia in the bilateral lower extremities with the accumulation of 18fluoro
      2-deoxyglucose (FDG) in the bilateral cauda equina. Cerebrospinal fluid cytology
      (three times) and flow cytometry (two times) and biopsies of the left sural
      nerve, bone marrow, paranasal sinus and left testis were all negative for
      malignancy, so finally we performed a surgical open biopsy of the cauda equina by
      laminectomy and diagnosed him with diffuse large B-cell lymphoma in the cauda
      equina. He was successfully treated with the disappearance of the FDG
      accumulation for a long time. The present case suggested that an early open
      biopsy of the cauda equina may be considered for cases of suspected
      neurolymphomatosis in the cauda equina for a good outcome.

PMID- 30101915
TI  - Ventricular Fibrillation Induced by Coronary Vasospasm in a Patient with Early
      Repolarization and Hyperthyroidism.
AB  - Vasospastic angina (VSA) has been recognized as a cause of ventricular
      fibrillation (VF) degenerating into sudden cardiac death. We experienced a case
      of VSA with hyperthyroidism in which VF was provoked with an augmented J-wave
      amplitude in the inferior leads. The patient underwent insertion of an
      implantable cardioverter-defibrillator for the secondary prevention of VF in
      addition to taking Ca-channel antagonists. He has shown no recurrence of fatal
      arrhythmia or anginal attack for a follow-up period of one year.

PMID- 30101917
TI  - An Acquired Epidermal Growth Factor Receptor T790M Mutation after the Addition of
      Bevacizumab to Preceding Erlotinib Monotherapy in a Lung Cancer Patient with
      Leptomeningeal Metastases.
AB  - A 53-year-old man with advanced lung adenocarcinoma harboring epidermal growth
      factor receptor (EGFR) exon 19 deletion received erlotinib. After 12 months of
      disease control with erlotinib monotherapy, leptomeningeal metastases (LM)
      occurred. A cerebrospinal fluid examination demonstrated a pre-existing EGFR exon
      19 deletion. Bevacizumab was combined with erlotinib, and the LM improved. After
      six months of combination therapy, however, the LM was exacerbated. A re
      examination of the cerebrospinal fluid revealed a T790M mutation and exon 19
      deletion. Osimertinib was administered, and the LM improved. The combination of
      bevacizumab and erlotinib was effective for erlotinib-resistant LM and resulted
      in the expression of a newly acquired T790M mutation, which enabled successful
      treatment with osimertinib.

PMID- 30101918
TI  - CT-guided Biopsy for the Diagnosis of Pulmonary Epithelioid Hemangioendothelioma
      Mimicking Metastatic Lung Cancer: A Case Report.
AB  - A 69-year-old male patient presented with multiple lung nodules revealed by chest
      computed tomography (CT) during a preoperative examination for an appendiceal
      tumor. The nodule diameters ranged from 2-10 mm without either pleural thickening
      or effusions. A fluorine-18-labeled fluorodeoxyglucose (18F-FDG)-positron
      emission tomography (PET)/CT scan showed a high FDG uptake in the appendiceal
      tumor, but almost normal standardized uptake values in the bilateral lung
      nodules. A CT-guided biopsy led to a diagnosis of pulmonary epithelioid
      hemangioendothelioma, a rare vascular tumor with a radiological presentation
      similar to that of a metastatic lung tumor. The present case is the first to
      describe successful treatment using a CT-guided biopsy instead of more
      conventional methods.

PMID- 30101919
TI  - An Arrhythmogenic Large Coronary Artery Aneurysm.

PMID- 30101920
TI  - Hypoglycemia Unawareness in Insulinoma Revealed with Flash Glucose Monitoring
      Systems.
AB  - The delayed diagnosis of insulinoma remains a clinical issue. One of the main
      causes of such a delay is hypoglycemia unawareness. A 53-year-old woman fell
      unconscious during postprandial exercises. Flash glucose monitoring (FGM) systems
      revealed glucose profiles with fasting hypoglycemia, which facilitated the
      clinical diagnosis of insulinoma even though she was unaware of her hypoglycemia.
      The preoperative comparison of the blood glucose values provided by FGM with
      those obtained from capillary blood were consistent. Thus, FGM may have potential
      utility in revealing the presence of insulinoma-induced hypoglycemia.

PMID- 30101921
TI  - First Nationwide Survey of 199 Patients with Amyloid A Amyloidosis in Japan.
AB  - Objective To clarify the underlying diseases, clinical manifestations, and
      treatment strategies for Amyloid A (AA) amyloidosis (AAA) in Japanese patients.
      Methods We conducted a survey on Japanese patients with AAA treated between
      January 1, 2012, and December 31, 2014. Results A total of 199 patients with AAA
      were included in the present study. The underlying diseases of AAA were
      rheumatoid arthritis (60.3%), uncharacterized inflammatory disorders (11.1%),
      neoplasms (7.0%), other rheumatic diseases (6.5%), inflammatory bowel diseases
      (4.5%), chronic infection (4.5%), Castleman's disease (4.0%), and
      autoinflammatory diseases (2.0%). The clinical manifestations at the diagnosis of
      AAA were moderate to severe renal dysfunction (46.2%), moderate to severe
      proteinuria (30.7%), intractable diarrhea (32.2%), melena (4.5%), paralytic ileus
      (3.5%), heart failure (11.6%), cardiac conduction disturbances (10.1%),
      arrhythmia (5.5%), and hypothyroidism (11.6%). Diagnostic biopsies were performed
      most frequently in the gastrointestinal tract (66.3%), followed by the kidneys
      (22.1%), heart (5.5%), abdominal fat (4.0%), and others (3.0%). Biologics were
      used to treat 97 patients with AAA (48.7%). Tocilizumab (TCZ) was administered to
      66 patients, with 95.5% showing good responses. Anti-TNF agents were administered
      to 27 patients, with 74.1% showing good responses. The treatment effects of TCZ
      were significantly superior to those of anti-TNF agents (p<0.007). Conclusion The
      most common underlying diseases of AAA were rheumatic diseases. Uncharacterized
      inflammatory disorders and neoplasms were also frequently observed in patients
      with AAA. Renal and gastrointestinal manifestations were common and important for
      the diagnosis of AAA, with cardiac manifestations also being of significance.
      Biologics, particularly TCZ, were effective therapeutic modalities.

PMID- 30101922
TI  - Fatal Neutropenic Enterocolitis Caused by Stenotrophomonas maltophilia: A Rare
      and Underrecognized Entity.
AB  - Although Stenotrophomonas maltophilia causes substantial morbidity and mortality
      in immunocompromised patients, it has not been described as a causal pathogen of
      neutropenic enterocolitis (NEC). We describe the first case of histologically
      confirmed NEC caused by S. maltophilia accompanied by bacteremia and pneumonia
      after salvage chemotherapy for acute myeloid leukemia relapse following a second
      hematopoietic stem cell transplantation. S. maltophilia should be included as a
      pathogenic organism of NEC in severely immunocompromised patients to prevent a
      delayed diagnosis, which carries a high risk of inappropriate antimicrobial
      selection and fatal outcome.

PMID- 30101923
TI  - Acute Non-calcific Retropharyngeal Tendinitis.

PMID- 30101924
TI  - Diabetic Nephropathy: A Comparison of the Clinical and Pathological Features
      between the CKD Risk Classification and the Classification of Diabetic
      Nephropathy 2014 in Japan.
AB  - Diabetic kidney disease is the main cause of end-stage kidney disease. However,
      the clinical manifestations of diabetic kidney disease are diverse. Therefore,
      the clinical classification of diabetic kidney disease is clinically important
      and valuable. In Japan, two clinical staging systems divided by the estimated
      glomerular filtration rate (eGFR) and albuminuria can be used for diabetic kidney
      disease: the chronic kidney disease (CKD) risk classification and the Japanese
      classification of diabetic nephropathy. The Japanese classification of diabetic
      nephropathy and the CKD risk classification are similar; however, these two
      classification systems show different frequencies of outcomes. For example, the
      frequency of the kidney outcomes in stage 4 of the Japanese classification of
      diabetic nephropathy was found to be higher than that in the red stage of the CKD
      risk classification (composite kidney events: stage 4=32.0/100 person-years, red
      =14.5/100 person-years). However, there were no marked differences in the speed
      or rate of decline in the kidney function (speed: stage 4=6.8 mL/min/1.73
      m2/year, red =5.8 mL/min/1.73 m2/year; rate: stage 4=38.8%/year, red =34.3%/year)
      or in the pathological changes between the two classifications. These data
      indicate that each stage of these clinical classification systems has
      characteristic clinical and pathological features. Therefore, it is important to
      understand each characteristic feature and use each classification system
      appropriately.

PMID- 30101925
TI  - An Autopsy Case of Familial Neuronal Intranuclear Inclusion Disease with Dementia
      and Neuropathy.
AB  - Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative
      disease with marked variety in its clinical manifestations. While characteristic
      neuroimaging and skin biopsy findings are important clues to the diagnosis,
      autopsy studies are still important for confirming the exact disease features. We
      herein report the case of a patient who received an antemortem diagnosis of
      familial NIID with dementia-dominant phenotype that was later confirmed by an
      autopsy. Our report is the first to document a case of autopsy-confirmed NIID
      involving both cognitive impairment and sensorimotor neuropathy.

PMID- 30101926
TI  - A Case of Primary Pulmonary Colloid Adenocarcinoma: How Can We Obtain a Precise
      Diagnosis?
AB  - A 76-year-old asymptomatic man was found to have a mass in the right lower lung
      field. Although the presence of a mucinous component in the majority of the tumor
      was shown by magnetic resonance imaging, the presence of cancer cells was
      suspected by contrast enhancement on computed tomography (CT) and based on the
      partial accumulation in the marginal regions of the tumor on fluorodeoxyglucose
      positron emission tomography (FDG-PET). A transbronchial lung biopsy was non
      diagnostic, but resection of the mass resulted in a diagnosis of colloid
      adenocarcinoma. The findings from combined contrast CT and FDG-PET may raise the
      suspicion of colloid adenocarcinoma and prompt the consideration of surgical
      resection.

PMID- 30101927
TI  - Post-hyperventilation Apnea with Spindle Activity on Electroencephalogram: A Case
      Report.
AB  - Loss of consciousness occurs in post-hyperventilation apnea, but its
      pathophysiology remains unclear. We herein report a patient with post
      hyperventilation apnea showing spindle activity on electroencephalogram (EEG).
      The patient was alert and breathing spontaneously before the hyperventilation
      test, but loss of consciousness and apnea with spindle activity on EEG occurred
      when the end-tidal CO2 decreased during the hyperventilation test. She recovered
      consciousness and spontaneous breathing with the disappearance of the spindle
      activity on EEG when the end-tidal CO2 increased after the hyperventilation test.
      The loss of consciousness during post-hyperventilation apnea might be due to the
      focal involvement of the ascending-activating mesodiencephalic reticular
      formation.

PMID- 30101928
TI  - Type 1 Diabetes Mellitus Diagnosed during Follow-up of Gestational Diabetes
      Mellitus in the Early Postpartum Period.
AB  - A 27-year-old woman with a history of gestational diabetes mellitus (GDM)
      developed type 1 diabetes mellitus (T1D) in the early postpartum period. Women
      with a history of GDM are at an increased risk of developing T1D, which is rarer
      than type 2 diabetes mellitus. A postpartum follow-up 75-g oral glucose tolerance
      test and the measurement of glutamic acid decarboxylase autoantibodies aided in
      the early detection of T1D in this patient. Careful attention should be paid to
      women with a history of GDM who exhibit clinical features suggestive of future
      development of T1D.

PMID- 30101929
TI  - Improvement of Mycobacterium abscessus Pulmonary Disease after Nivolumab
      Administration in a Patient with Advanced Non-Small Cell Lung Cancer: A Case
      Report.
AB  - Nivolumab has become the standard second-line chemotherapy for non-small cell
      lung cancer. A 73-year-old man with stage IV non-small cell lung cancer received
      6 cycles of chemotherapy with nab-paclitaxel/carboplatin/bevacizumab followed by
      11 cycles of nab-paclitaxel/bevacizumab; however, treatment was stopped due to
      pneumothorax. One year after therapy started, a nodule appeared in the left upper
      lung and increased in size. Mycobacterium abscessus subsp. massiliense disease
      was diagnosed by a sputum analysis. After short antibiotic treatment, nivolumab
      was administered. Two months after nivolumab treatment, the nodule improved along
      with a good tumour response. The effectiveness of nivolumab for chronic
      infectious diseases, such as M. abscessus disease, should be investigated.

PMID- 30101930
TI  - Usefulness of a Newly Developed Spirometer to Measure Dynamic Lung Hyperinflation
      following Incremental Hyperventilation in Patients with Chronic Obstructive
      Pulmonary Disease.
AB  - Objective This study was performed to determine the usefulness of a newly
      developed spirometer for the quantitative assessment of dynamic lung
      hyperinflation (DLH) following incremental hyperventilation in chronic
      obstructive pulmonary disease (COPD). Methods The subjects were 54 patients with
      COPD and 25 healthy volunteers. Each subject was asked to hyperventilate for 30 s
      with stepwise increments starting at the resting respiration rate and increasing
      to respiratory rates of 20, 30, and finally 40 breaths/min while using a newly
      developed spirometer. The relationship between the observed inspiratory capacity
      (IC) reduction following incremental hyperventilation as an index of DLH and
      spirometry or the 6-minute walking distance was examined. Results The IC did not
      decrease significantly from the resting IC, even when the respiratory rate was
      increased, in the healthy volunteer group. However, in the COPD patient group,
      the IC decreased with increases in the respiratory rate. Significant correlations
      were found between all IC parameters and the severity of COPD. A significant
      negative correlation was also found between the decreased IC and the 6-minute
      walking distance. Conclusions These findings suggest that the quantitative
      assessment of DLH following incremental hyperventilation using the newly
      developed spirometer may be useful for the assessment of pathophysiological
      impairment in patients with COPD.

PMID- 30101931
TI  - Hyperthyroidism with Selective Immunoglobulin A Deficiency.

PMID- 30101932
TI  - Pulmonary Scedosporium apiospermum Infection with Pulmonary Tumorlet in an
      Immunocompetent Patient.
AB  - Scedosporium apiospermum is an opportunistic fungus that can cause various types
      of infections, including localized infections and life-threatening disseminated
      infections, particularly in immunocompromised patients. Treatment is especially
      challenging due to its multidrug resistance. We herein report the case of a 73
      year-old woman who was non-immunocompromised but developed S. apiospermum lung
      infection and a pulmonary tumorlet. To our knowledge, this is the first report of
      the coexistence of pulmonary S. apiospermum infection and tumorlet. The lung
      lesion was successfully treated by surgical excision without any antifungal
      agents, and no recurrence of the tumorlet or S. apiospermum infection has
      occurred.

PMID- 30101933
TI  - Fibrolamellar hepatocellular carcinoma with multiple lung metastases treated with
      multidisciplinary therapy.
AB  - A 20-year old man was diagnosed with fibrolamellar hepatocellular carcinoma
      (FLHCC) with multiple lung metastases, and chemotherapy with FOLFOX was
      administered. Contrast enhanced CT after 3 cycles of FOLFOX showed no disease
      progression. We therefore performed surgical resection and radiofrequency
      ablation of the liver lesions and lung metastases, after obtaining the patient's
      informed consent. The liver lesions and lung metastases tested positive for
      DNAJB1-PRKACA. The treatment for FLHCC with extrahepatic metastasis has not been
      established; however, in a few cases, good long-term prognoses were obtained with
      multidisciplinary therapy. We herein report a case of FLHCC with multiple lung
      metastases that was treated with multidisciplinary therapies.

PMID- 30101934
TI  - A Case of Severe Osteomalacia with Dent Disease Caused by a Novel Intronic
      Mutation of the CLCN5 gene.
AB  - We present a case of Dent disease caused by a novel intronic mutation, 1348-1G>A,
      of the chloride voltage-gated channel 5 (CLCN5) gene. Cultured proximal tubule
      cells obtained from the patient showed impaired acidification of the endosome
      and/or lysosome, indicating that the 1348-1G>A mutation was indeed the cause of
      Dent disease. Although the prevalence of osteomalacia in Dent disease is low in
      Japan, several factors-including poor medication adherence-caused severe
      osteomalacia in the current case. Oral supplementation with calcium and
      native/active vitamin D therapy, with careful attention to medication adherence,
      led to the improvement of the patient's bone status.

PMID- 30101935
TI  - Pulmonary Hyalinizing Granuloma Mimicking Primary Lung Cancer.
AB  - We herein report a case of pulmonary hyalinizing granuloma (PHG), which is a rare
      pulmonary mass. A 69-year-old man with no symptoms presented to our hospital
      because of the appearance of an abnormal shadow on chest X-ray. Computed
      tomography revealed a right middle-lobe mass with spicula and infiltration into
      the upper lobe. Since a bronchofiberscopic examination showed no malignant cells
      in the specimen, the patient underwent thoracoscopic surgery, which revealed PHG.
      Spiculation and interlobar infiltration, which comprise the characteristic
      features of primary lung cancer, are uncommon presentations of this rare entity.

PMID- 30101936
TI  - Negative Pressure Pulmonary Edema.

PMID- 30101937
TI  - Multiple Placental Infarcts in a Pregnant Woman with Essential Thrombocythemia: A
      Case Report.
AB  - Myeloproliferative neoplasms (MPNs), including polycythemia vera, essential
      thrombocythemia (ET), and primary myelofibrosis, mainly occur in older patients,
      but have also been reported in younger patients. A "second peak" occurs in female
      patients in their thirties, particularly in ET; thus, the management of pregnancy
      is often discussed. We herein present the case of a 33-year-old woman with a high
      platelet count and multiple placental infarcts during delivery who was
      subsequently diagnosed with ET. Although there are no worldwide guidelines for
      the management of MPNs in pregnancy, the risk of thrombosis is markedly increased
      in these patients, and antithrombotic therapy should be considered.

PMID- 30101938
TI  - Actinomycosis-induced Trismus with Orbital Involvement.

PMID- 30101939
TI  - A Case of Lambda Light Chain Non-crystalline Proximal Tubulopathy with IgD Lambda
      Myeloma.
AB  - Light Chain Proximal Tubulopathy (LCPT) is a rare form of paraprotein-related
      kidney disease in which monoclonal free light chains damage the proximal renal
      tubular epithelial cells. We herein report the case of a 78-year-old woman who
      presented with anemia and kidney dysfunction. Serum and urine protein
      electrophoresis analyses revealed a monoclonal IgD and lambda free light chains.
      Proximal tubular injury and the accumulation of lambda light chains were found by
      kidney biopsy. Electron microscopy revealed no organized structure suggestive of
      crystals. LCPT was caused by IgD lambda myeloma and bortezomib and dexamethasone
      therapy led to VGPR without a worsening of the kidney function.

PMID- 30101940
TI  - Is Severe and Long-lasting Linezolid-induced Optic Neuropathy Reversible?
AB  - Linezolid is a useful drug for treating drug-resistant tuberculosis. However, the
      associated toxicities, especially optic neuritis, are a major obstacle for its
      long-term use. We recently experienced a case of severe optic and peripheral
      neuropathy during the treatment of multidrug-resistant tuberculosis. The
      treatment continued for 12 months despite severe optic and peripheral neuropathy.
      At eight months after the discontinuation of the drug, the optic neuropathy
      recovered, but the peripheral neuropathy did not. Considering the grave prognosis
      of drug-resistant tuberculosis, the continuation of linezolid despite
      neurotoxicity under close observation may be a suitable option.

PMID- 30101941
TI  - Vertical and Circumferential Localization of Esophageal Mucosal Breaks in
      Patients with Mild Reflux Esophagitis.
AB  - Aim Esophageal mucosal breaks are considered to occur circumferentially in
      locations with high exposure to acid. In the present study, we investigated the
      circumferential localization of esophageal mucosal breaks based on their distance
      from the esophagogastric junction. Subjects and methods The vertical and
      circumferential localization of 625 esophageal longitudinal mucosal breaks was
      examined in 398 patients with mild reflux esophagitis. Results The number of
      mucosal breaks in which the distal end was located 0-1 cm from the
      esophagogastric junction was 454, while those in which the distal end was located
      1-2, 2-3, and >3 cm from the junction were 125, 28, and 18, respectively. There
      was a marked difference in the circumferential distribution among the groups
      defined by distance from that junction. Esophageal mucosal breaks whose distal
      end were located 0-1 cm from the esophagogastric junction were mainly found on
      the right anterior wall of the esophagus, while those located 1-2 cm from the
      junction were mainly found on the right wall, and those located 2-3 and >3 cm
      from the junction were mainly found on the posterior wall. Conclusion Esophageal
      mucosal breaks occurring relatively near the esophagogastric junction mainly
      exist on the right anterior wall, whereas those farther from that junction tend
      to exist on the posterior wall of the esophagus. The circumferential location of
      esophageal mucosa highly exposed to refluxed gastric contents changes based on
      the distance from the esophagogastric junction.

PMID- 30101942
TI  - Clinical and Pathological Characteristics of Elderly Japanese Patients with IgA
      Vasculitis with Nephritis: A Case Series.
AB  - Objective This case series aimed to identify the clinical and pathological
      characteristics of elderly patients (>=60 years) with biopsy-proven IgA
      vasculitis with nephritis (IgAVN). Methods The clinical and pathological
      presentation and treatment outcomes were compared between two groups. Patients
      Patients with IgAVN who were >=19 years old at the time of their renal biopsy
      were divided into elderly (>=60 years) and adult (19-59 years) groups. Results Of
      the 23 patients in our study, 13 were elderly. In the elderly group, the median
      age at the diagnosis was 68 years (range, 60-85 years), with a median follow-up
      period of 15 months (range, 3-80 months). Twelve elderly patients had
      comorbidities, including hypertension, diabetes mellitus, chronic kidney disease,
      cardiovascular disease, and malignancies. A decrease in the estimated glomerular
      filtration rate, as well as massive proteinuria and rapidly progressive nephritic
      syndrome, were more frequent in the elderly group than in the adult group.
      Furthermore, renal pathological changes, including cellular or fibrocellular
      crescents, interstitial fibrosis, tubular atrophy, and arteriosclerosis, were
      more severe among elderly patients than adult patients. All elderly patients were
      treated with glucocorticoids and had no incidence of end-stage renal disease at
      the final follow-up; in addition, nine elderly patients had reduced proteinuria
      with a preserved renal function. Adverse events, including infection, diabetes
      mellitus, and vascular disorders, were identified in nine patients. Three elderly
      patients died from severe infections. Conclusion IgAVN in elderly patients is
      characterized by severe renal involvement. Elderly patients are at higher risk
      than adults for treatment-related adverse events.

PMID- 30101943
TI  - A Case of Nonbacterial Thrombotic Endocarditis Concomitant with Repeated Systemic
      Embolization That Received Palliative Care Based on the Antemortem Diagnosis.
AB  - A 67-year-old woman was admitted to our hospital due to an acute onset of
      consciousness disturbance, aphasia and left hemiplegia. Computed tomography
      revealed multiple systemic infarctions, including brain, kidney and spleen.
      Transesophageal echocardiography revealed vegetations attached to the mitral
      valve leaflets, which was suspected to be the embolic source. Repeated blood
      cultures were negative, and advanced lung cancer was incidentally revealed by
      computed tomography. She was then diagnosed with nonbacterial thrombotic
      endocarditis (NBTE) based on the overall clinical picture. Subsequently,
      extensive systemic embolization repeatedly occurred, but she eventually died 25
      days after admission. The autopsy proved NBTE and advanced-stage lung
      adenocarcinoma.

PMID- 30101944
TI  - Intravenous Cyclophosphamide for Gastric Antral Vascular Ectasia Associated with
      Systemic Sclerosis Refractory to Endoscopic Treatment: A Case Report and Review
      of the Pertinent Literature.
AB  - Gastric antral vascular ectasia (GAVE) is a rare cause of chronic gastric
      hemorrhaging and iron deficiency anemia and is characterized by a distinctive
      endoscopic appearance. The main treatment of GAVE is endoscopic; however,
      medication is necessary in refractory cases. We herein report a 69-year-old woman
      with systemic sclerosis (SSc) who developed recurrent severe anemia after
      endoscopic treatment of GAVE that was successfully managed using intravenous
      cyclophosphamide (IVCY). The recurrence of GAVE after discontinuation of IVCY was
      successfully managed using a combination of IVCY and endoscopic treatment,
      without blood transfusion. Long-term IVCY may be indicated for refractory GAVE
      associated with SSc.

PMID- 30101945
TI  - Catheter-induced Spasm in the Proximal Right Coronary Artery.
AB  - Objectives The clinical characteristics in patients with catheter-induced spasm
      in the proximal right coronary artery (RCA) are controversial. We performed a
      clinical analysis of catheter-induced spasm in the RCA. Methods We
      retrospectively analyzed 5,352 consecutive patients who underwent diagnostic or
      follow-up angiography during a 26-year period. During this period, we found 40
      patients with catheter-induced spasm in the RCA. We compared the clinical
      characteristics and procedures of cardiac catheterization in patients with
      catheter-induced spasm in the RCA with those in patients without such spasm.
      Results The frequency of catheter-induced spasm in the RCA was 0.75% (40/5,352).
      We performed pharmacological spasm provocation tests in 36 of 40 patients after
      spasm relief. Positive spasm was observed in 32 patients (88.9%), and 25 patients
      (78.1%) had multiple spasms. The catheter procedures, including the approach
      sites (radial/brachial/femoral), catheter size (4/5/6 Fr) and catheter type
      (Judkins right/Sones/Shared/Judkins left 3.5/Amplatz) were not markedly different
      between the two groups. A multivariate analysis showed that positive spasm (odds
      ratio [OR]: 7.030, 95% confidence interval [CI]: 1.920-25.700), a younger age
      (OR: 0.937, 95% CI: 0.910-0.965) and diabetes mellitus (OR: 0.278, 95% CI: 0.083
      0.928) were the determinant factors for the catheter-induced spasm. Conclusion
      Approximately 80% of patients with catheter-induced spasm in the proximal RCA had
      coronary spastic angina. Positive provoked spasm was the most powerful
      determinant factor for catheter-induced spasm.

PMID- 30101946
TI  - The Cerebellar Leptomeningeal Enhancement Associated with Cryptococcal
      Meningitis.

PMID- 30101947
TI  - CBCT imaging of the alveolar bone structure in maxilla of elderly donor cadavers
      and PCA analysis.
AB  - There is an important bone matrix with remodelling between dentate and edentulous
      samples of the human maxilla for bone metabolism. Cone beam computed tomography
      (CBCT) is useful for structural analysis of bone. The objective of this study was
      to investigate morphological data of donor cadavers in detail using CBCT imaging
      and principal component analysis (PCA). We analysed 38 donor cadavers using a
      CBCT apparatus. The analytical results defined differences in skull measurement
      parameters and dentate and edentulous levels using PCA. We observed cortical
      bone, trabecular bone, and the distance from the bottom of the maxillary sinus to
      the oral mucosa at a right angle to the palatal plane of the first molar region
      between dentate and edentulous samples of the human maxilla using CBCT imaging.
      In the dentate sample of the maxilla, component 1 was defined by negative
      contributions from gender (-0.84) and age (-0.54) to positive contributions such
      as cortical bone structure (CBS, 0.68) and trabecular bone structure (TBS, 0.50).
      There was a difference in CBS between dentate and edentulous human maxilla
      samples. This study of CBCT data provides useful basal information for planning
      dental implant surgery using PCA.

PMID- 30101948
TI  - Morphology of the lingual papillae of the Chapman's zebra (Equus quagga
      chapmani).
AB  - We examined the dorsal lingual surfaces of an adult Chapman's zebra by scanning
      electron microscopy. The filiform papillae of the lingual apex consisted of a
      main papilla and smaller secondary papillae. The fungiform papillae were round in
      shape. The filiform papillae of central region of the lingual body were needle
      like in shape. The filiform papillae of posterior region of the lingual body were
      hair-like in shape. Many grooves were observed on posterolateral regions and the
      fungiform papillae were observed on the inside of some grooves. The vallate
      papillae were located on both sides of the posterior region and surrounded by a
      groove. The anatomical characteristic of the lingual surface of the Chapman's
      zebra is the fungiform papillae on the inside of some grooves.

PMID- 30101949
TI  - Morphology of the lingual papillae in the Asian golden cat.
AB  - We microscopically examined the dorsal lingual surface of an adult Asian golden
      cat (Catopuma temminckii). The papillae on the margin of the lingual apex were
      horny-shaped and fungiform. The filiform papillae on the anterior part of the
      lingual body were large and cylindrical; the connective tissue core of each of
      these comprised a large conical papilla. The filiform papillae on the central
      part of the lingual body were large and conical-shaped on the medial side and
      dome-shaped on the lateral side. The connective tissue core of each medial
      filiform papilla comprised a large main process and some secondary processes,
      while processes were absent on the lateral side. These findings are peculiar to
      the tongue of members of the family Felidae.

PMID- 30101950
TI  - Quantification of voxel values in micro computed tomography using multiple
      porosity hydroxyapatite blocks.
AB  - Microfocus X-ray computed tomography (micro-CT) has been applied as a method for
      the nondestructive and detailed assessment of trabecular bone patterns and tooth
      structure. Voxel values obtained from micro-CT are not absolute values.
      Therefore, voxel values were assessed using hydroxyapatite (HA) blocks with a
      different vesicle rate to quantify voxel values of micro-CT images in the present
      investigation.HA blocks with 4 levels of porosity and a block with a soft tissue
      equivalent density were used, and the voxel values of each block were measured.
      Correlations between voxel values of micro-CT and HA densities were analyzed.
      Also, black and white binary images were produced, and the ratios of white pixels
      to pixels in regions of interest (ROIs) were calculated. The relationship between
      voxel values of micro-CT and HA densities could be regressed using a linear
      equation, and the correlation coefficient was high. Also, there were no
      significant differences in the regression equations between the first and second
      times. Voxel values of micro-CT might be convertible to HA densities using a
      regression equation.

PMID- 30101952
TI  - Syntheses, structures and magnetic properties of macrocyclic Schiff base
      supported homodinuclear lanthanide complexes.
AB  - Five new homodinuclear lanthanide complexes with the general formula
      [(acac)4Ln2(L)] (Ln3+ = Dy3+ (1), Tb3+ (2), Ho3+ (3), Er3+ (4), and Gd (5)) were
      synthesized by one-pot [2 + 2] condensation of 2,6-diformyl-4-methylphenol and
      1,3-diaminopropane in the presence of various lanthanide acetylacetonates. The
      eight-coordinate Ln(iii) centre adopts a slightly distorted square antiprism
      geometry with D4d symmetry. Theoretical analysis and magnetic measurements reveal
      that the corresponding Dy complex 1 exhibits slow magnetic relaxation behavior,
      characteristic of a typical SMM with the intramolecular ferromagnetic Dy3+Dy3+
      interaction.

PMID- 30101951
TI  - Effect of Resourcefulness Training on Symptoms Distress of Patients with
      Nasopharyngeal Carcinoma.
AB  - BACKGROUND Symptom distress is very common in patients with nasopharyngeal
      carcinoma (NPC) during radiotherapy, seriously affecting their quality of life
      and impeding the process of rehabilitation. Resourcefulness training can enhance
      the level of resourcefulness and benefit-finding, palliate symptom distress, and
      promote disease rehabilitation. However, the effects of resourcefulness training
      on local complications and benefit-finding in NPC patients during radiotherapy
      remains poorly understood. MATERIAL AND METHODS Questionnaires and
      resourcefulness training intervention were used in this study. The relationships
      among resourcefulness, benefit-finding, and symptom distress of 304 NPC patients
      were analyzed and the effects of resourcefulness training on NPC patients (N=80)
      were evaluated during radiotherapy. RESULTS Among the 304 NPC patients, age,
      educational level, occupation, family monthly income, method of payment of
      medical expenses, and histological types were significant factors influencing
      resourcefulness and benefit-finding. The patients' resourcefulness was positively
      correlated to their benefit-finding; and their distress was negatively correlated
      to their resourcefulness. After resourcefulness training for 2 months, average
      scores of the resourcefulness and benefit-finding were significantly increased in
      the intervention group (N=40) compared to those in the control group (N=40).
      Average scores of symptom distress were significantly reduced in the 2 groups,
      but they were reduced more significantly in the intervention group than in the
      control group. CONCLUSIONS The patients' benefit-finding and symptom distress
      were correlated with their resourcefulness. Resourcefulness training could
      enhance the level of resourcefulness and benefit-finding, palliate symptom
      distress, and promote disease rehabilitation in NPC patients during radiotherapy.

PMID- 30101953
TI  - Organometallic MTCNQ films: a comparative study of CuTCNQ versus AgTCNQ.
AB  - We performed a systematic study of electron-acceptor molecules in two closely
      related organometallic solids, namely, CuTCNQ and AgTCNQ. These studies were
      performed using both an experimental approach, via the use of electron
      spectroscopies (XPS and UPS), and a theoretical approach, via the use of ab
      initio DFT calculations. From these results, a complete description of the
      electronic structure of these molecular solid-films could be given, identifying
      the characteristic electronic and structural features of each part of the
      molecules and their contribution to the final electronic structure. Empty states
      were found close to the Fermi level in both solids. The presence of an electronic
      band close to the Fermi level is related to the magnetic behavior predicted for
      both MTCNQ solids for their isolated monolayers. However, the lower work function
      of the MTCNQ with respect to the metal substrate one implies that the MTCNQ film
      accepts electron from the metal substrate, thus fulfilling its Fermi level band.
      This occupied band explains the absence of shake-up features in the core level
      spectra in opposition to the TCNQ. The UPS experiments indicated that the MTCNQ
      film was doped by a small excess of metal from the substrate, shifting the
      electron Fermi level close to the MTCNQ conduction band. Thus, the MTCNQ film
      becomes an n-type semiconductor, opening up a very interesting field in the
      technological applications of this system.

PMID- 30101959
TI  - Surface and interface design for photocatalytic water splitting.
AB  - Surface and interface structures are considered as the critical parameters which
      can be engineered to improve the performance of catalysts. This Frontiers article
      highlights our recent advances in surface and interface design toward
      photocatalytic water splitting.

PMID- 30101954
TI  - Rapid and sensitive detection of nodularin-R in water by a label-free BLI
      aptasensor.
AB  - Contamination of freshwater with nodularin-R (NOD-R) represents a significant
      global environmental and public health concern. However, ethical problems and
      technical difficulties surrounding the current detection methods for NOD-R
      necessitate further studies to devise appropriate alternatives within a
      regulatory monitoring regime. In this work, we employed an aptamer as a specific
      recognition element and developed a biolayer interferometry (BLI) biosensor
      platform for NOD-R detection. The aptasensor we propose displayed a broad
      detection range from 40 to 600 nM NOD-R (and a linear response range from 40 to
      200 nM), and achieved a detection limit as low as 167 pM. In addition, the
      aptamer-based biosensor was shown to possess high selectivity, as well as good
      reproducibility and stability. We believe that this novel aptamer-based biosensor
      provides a potential alternative for the sensitive and rapid detection of NOD-R.

PMID- 30101960
TI  - Ligand and solvent control of selectivity in the C-H activation of a pyridylimine
      substituted 1-naphthalene; a combined synthetic and computational study.
AB  - The pyridylimine-substituted 1-naphthalenes, 2-(1-C10H7)-6-{CR[double bond,
      length as m-dash]N(2,6-i-Pr2C6H3)}C5H3N (R = Me HLMe, H HLH), react with
      Na2[PdCl4] in acetic acid at elevated temperature to afford either ortho-C
      Hnaphthyl activated (LMe)PdCl (2ortho) or the unactivated adduct (HLH)PdCl2 (1b).
      Alternatively, 1b and its ketimine analogue (HLMe)PdCl2 (1a), can be prepared by
      treating (MeCN)2PdCl2 with either HLMe or HLH in chloroform at room temperature.
      Regio-selective ortho-C-H activation to form 2ortho can also be initiated by the
      thermolysis of 1a in acetic acid, while no reaction occurs under similar
      conditions with 1b. Interestingly, the C-H activation of HLMe to give 2ortho is
      found to be reversible with 100% deuteration of the peri-site occurring on
      reacting Na2[PdCl4] with HLMe in acetic acid-d4. By contrast, heating 1a in
      toluene gives a 55 : 45 mixture of 2ortho and its peri-activated isomer 2peri.
      Pure 2peri can, however, be obtained either from (LMe)PdOAc (3peri) by OAc/Cl
      exchange or by the sequential reactions of 1a with firstly silver acetate then
      with aqueous sodium chloride. Intriguingly, a peri to ortho interconversion
      occurs on heating 2peri in acetic acid to give 2ortho. DFT calculations have been
      used to investigate the C-H activation steps and it is found that in acetic acid
      ortho-C-H activation is kinetically and thermodynamically favoured but peri-CH
      activation is kinetically accessible (DeltaDeltaG? = 2.4 kcal mol-1). By contrast
      in toluene, the reaction appears to be irreversible with the difference in
      barrier height for ortho- and peri-C-H activation being very small within the
      error of the method (DeltaDeltaG? = 0.7 kcal mol-1), findings that are in
      agreement with the empirically observed product distribution for 2ortho and
      2peri. Single crystal X-ray structures are reported for 1a, 1b, 2ortho and 2peri.

PMID- 30101961
TI  - Encapsulating metal nanoparticles inside carbon nanoflakes: a stable absorbent
      designed from free-standing sandwiched composites.
AB  - Combination of carbon and metal materials is a good strategy to develop
      lightweight microwave absorbents. Taking advantage of the encapsulation property
      of carbon nanoflakes, a stable microwave absorber could be achieved. In this
      study, we managed to achieve sandwich-shaped Ni/C nanoflakes via a simple route
      involving a one-step hydrothermal method towards Ni(OH)2 nanosheets, followed by
      a calcination procedure. These sandwiched carbon nanoflakes not only increased
      the interfacial polarization, but also resulted in the absolute stability of
      metal nanoparticles. Considering the higher possibility of some support plates to
      be wrinkled, which would bring about imperfect sandwiched structures, the free
      standing sandwiched composites were in a relatively good shape. Furthermore, the
      intensive conductive loss could be highly responsible for better microwave
      absorption properties by adjusting the carbonization temperature. The minimum
      reflection loss (RL) value of Ni/C composites that were obtained with a 25%
      loading filler ratio could reach -24.3 dB with a matching thickness of only 1.5
      mm. Moreover, the effective microwave absorption bandwidth (<-10 dB) could reach
      to 4.0 GHz with thicknesses of both 1.3 mm and 1.4 mm. Therefore, the sandwich
      shaped Ni/C nanoflakes could be exploited as an effective and lightweight
      microwave absorber.

PMID- 30101962
TI  - Effects of a low and a high dietary LA/ALA ratio on long-chain PUFA
      concentrations in red blood cells.
AB  - There is a debate about the optimal dietary ratio of the parent n6 fatty acid
      linoleic acid (LA) and n3 fatty acid alpha-linolenic acid (ALA) to promote an
      efficient conversion of ALA to EPA and DHA, which have implications for human
      health. The aim of the present study was to compare the effects of a low-LA/high
      ALA (loLA/hiALA) diet with a high-LA/low-ALA (hiLA/loALA) diet on fatty acid
      concentrations in red blood cells (RBCs). Fifteen omnivore healthy men (mean age
      26.1 +/- 4.5 years) with a low initial EPA/DHA status (sum (?) EPA + DHA% of
      total fatty acids in RBC at baseline: 4.03 +/- 0.17) received both diets for two
      weeks with a nine-week wash-out phase in between. Fatty acid intake of the
      subjects was tightly controlled. Concentrations [MUg mL-1] and relative amounts
      [% of total fatty acids] of fatty acids in RBCs were analyzed at baseline (day
      0), day 7 and 14 by means of GC-FID. The dietary LA/ALA ratios were 0.56 +/- 0.27
      : 1 and 25.6 +/- 2.41 : 1 and led to significantly different changes of ALA, LA,
      EPA and ?EPA + DHA concentrations in RBCs. In the course of the loLA/hiALA diet
      ALA and EPA concentrations and relative amounts of ?EPA + DHA increased, whereas
      LA concentrations decreased. The DHA concentration was unaffected. The hiLA/loALA
      diet led to slightly decreased EPA concentrations, while all other fatty acid
      concentrations remained constant. Compared to our previous study, where we simply
      increased the ALA intake, our results show that ALA supplementation combined with
      a reduced LA intake (loLA/hiALA diet) more efficiently enhanced EPA blood
      concentrations. The absence of changes in the PUFA pattern in consequence of a
      LA/ALA ratio of 25.6 +/- 2.41 : 1 suggests that the high LA/ALA ratio of the
      Western diet already leads to a saturation and a further increase of the ratio
      does not affect the PUFA pattern.

PMID- 30101963
TI  - Synthesis of new fluorinated proline analogues from polyfluoroalkyl beta
      ketoacetals and ethyl isocyanoacetate.
AB  - The reaction of trifluoroaldol acetal and other polyfluoroalkyl beta-ketoacetals
      with ethyl isocyanoacetate was applied for the preparation of hitherto unknown
      fluorinated amino acids, cis- and trans-3-CF3/C2F5-prolines as well as trans-3
      CF2Br/CF2Cl/CHF2-3-hydroxyprolines.

PMID- 30101965
TI  - Five monocyclic pyridinium derivative based halo-argentate/cuprate hybrids or
      iodide salts: influence of composition on photochromic behaviors.
AB  - The rational choice of an electron acceptor was proved to be an effective
      strategy for the development of novel electron transfer (ET) photochromic
      iodides, but the types and amounts of reported electron acceptors are relatively
      limited so far, especially for monocyclic aromatic molecules. Herein, using
      monocyclic pyridinium derivatives (N-protonation-4-carboxypyridinium/N
      protonation-4-carbamoylpyridinium/1-methyl-4-(carbomethoxy)pyridinium) as
      structural directing agents and electron acceptors, five new electron donor
      acceptor-based halo-argentate/cuprate hybrids or iodide salts have been
      synthesized, including [HINA][Ag4I5] (1), [HINAM]I (2), [HINAM]I.0.5(I2) (3),
      [MCMP][Ag2Br3] (4) and [MCMP][Cu2I3] (5). Noteworthily, compounds 1-3 exhibit
      interesting photochromic behaviours, while compounds 4 and 5 are non
      photochromic. Finally, the possible chromic mechanisms and influencing factors
      for the title compounds were also discussed.

PMID- 30101966
TI  - Walnut diets up-regulate the decreased hippocampal neurogenesis and age-related
      cognitive dysfunction in d-galactose induced aged rats.
AB  - Recently, dietary intervention has been considered as a prospective strategy in
      delaying age-related cognitive dysfunction and brain plasticity degeneration.
      This study explored the effect of walnut diets (6% and 9%, 8 weeks) on cognitive
      behavior, hippocampal neurogenesis and the neurotrophic signaling pathway in d
      galactose (d-gal) model rats. Behavioral tests showed that walnut diets
      significantly reversed spatial memory loss in the Morris water test, locomotor
      activity deficiency in an open field test, and a recognition behavior reduction
      in a novel object recognition task. Immunohistochemistry analysis demonstrated
      walnut diets significantly increased the hippocampal neurogenesis in d-gal model
      rats. Moreover, western blot results indicated that walnut diets reserved a d-gal
      induced decrease of hippocampal pCREB (Ser133) and BDNF expression, two crucial
      intracellular molecules involved in hippocampal neurogenesis. These findings
      confirmed that chronic walnut-rich diets could ameliorate cognitive dysfunction
      in d-gal model rats, and the up-regulation of neurogenesis, as well as the
      expression of pCREB and BDNF in hippocampus, may be one of the molecular and
      cellular mechanisms underlying these effects.

PMID- 30101967
TI  - Refinement of the crystal structure of Li4P2S6 using NMR crystallography.
AB  - The structure of Li4P2S6 was solved, based on a combination of X-ray powder
      diffraction data, quantum chemical calculations and solid state nuclear magnetic
      resonance (NMR). Two-dimensional 31P single quantum/double quantum correlation
      spectra yielded important constraints regarding the space group symmetry allowing
      the crystal structure to be solved by the Rietveld method. Li4P2S6 crystallizes
      in a trigonal space group with a = 10.51452(6) A; c = 6.59149(8) A. The structure
      contains two distinct P2S64- ions in a 2 : 1 ratio: in the first one the two P
      atoms of the hexahypothiophosphate unit are crystallographically distinct,
      whereas in the second one they are crystallographically identical.

PMID- 30101969
TI  - Outerly functionalized and non-functionalized boron clusters intercalated into
      layered hydroxides with different modes of binding: materials for superacid
      storage.
AB  - Two binary boron hydrides (NH4)2B10H10 and Na2B12H12 and mono- and dicarboxy p-
      and m-carboranes (namely, 1-(COOH)-closo-1,7-C2B10H11, 1,12-(COOH)2-closo-1,12
      C2B10H10 and 1,7-(COOH)2-closo-1,7-C2B10H10) were intercalated into ZnAl-layered
      double hydroxides (ZnAl-LDH) and into Zn5(OH)8(NO3)2.2H2O. The formed compounds
      were characterized using elemental analysis, thermogravimetry analysis, X-ray
      powder diffraction, infrared spectroscopy and solid state NMR. All the
      intercalated boron compounds are present in the interlayer space of the layered
      hosts as anions. It is presumed that in the case of B10H102-, B12H122- and 1,12
      (COO)2-closo-1,12-C2B10H102-, the guest molecules form a monolayer, whereas in
      the case of 1-(COO)-closo-1,7-C2B10H111- and 1,7-(COO)2-closo-1,7-C2B10H102- a
      bilayer arrangement is more probable. In the case of 1,7-(COO)2-closo-1,7
      C2B10H102-, the guest molecules are strongly interdigitated resulting in lowering
      of the interlayer distance. Two different modes of binding were found. Whereas
      the carboxylate derivatives of p- and m-carboranes are bonded through classical
      hydrogen bonds, the corresponding parent borane anions interact with the host
      structures by mainly dihydrogen bonding. In effect, both kinds of hydrogen
      bonding are mainly of an electrostatic nature. The dihydrogen bond is detected,
      e.g. in crystal engineering, and represents a driving force for interactions of
      boranes with biomolecules. Since the latter dicarboxylic acids were found to be
      superacids, their interactions with the host structures should be stronger than
      in the case of the benzoic and terephthalic acid intercalates.

PMID- 30101970
TI  - Grit and self-discipline as predictors of effort and academic attainment.
AB  - BACKGROUND: Beyond ability, traits related to perseverance, such as grit and self
      discipline, are associated with adaptive educational outcomes. Few studies have
      examined the independent effects of these traits on outcomes and the mechanisms
      involved. AIMS: This study estimated parameters of a process model in which grit
      perseverance of effort (grit-effort) and consistency of interest (grit-interest)
      dimensions and self-discipline were independent predictors of students' science
      grades. The effect of the grit-effort on grades was expected to be mediated by
      students' self-reported effort on optional out-of-school science learning
      activities. SAMPLE: Secondary school students (N = 110) aged between 12 and 14
      years. METHODS: The study adopted a correlational design with measures taken on
      three occasions. Students completed self-report measures of grit and self
      discipline early in the semester and effort on optional out-of-school learning
      activities 5 weeks later. Students' science grades were collected at the end of
      the semester. Data were analysed using Bayesian path analyses using non
      informative and informative priors derived from previous research. RESULTS:
      Consistent with predictions, we found effects of grit-effort on science grades
      mediated by effort, and self-discipline on grades. Contrary to predictions, we
      also found an effect of self-discipline on grades mediated by effort. Zero was a
      credible value for direct effects of grit-effort on grades, and grit-interest on
      effort and grades. CONCLUSIONS: Results suggest grit-effort and self-discipline
      relate to effort on educational activities linked to better grades. The direct
      effect of self-discipline on grades suggests that it may be related to other
      activities that determine science attainment.

PMID- 30101971
TI  - BAMM gives misleading rate estimates in simulated and empirical datasets.
AB  - In a previous paper, we used simulations and empirical data to show that BAMM
      (Bayesian Analysis of Macroevolutionary Mixtures) can give misleading estimates
      of rates and rate shifts. In simulations, BAMM underestimated rate shifts across
      every tree analyzed, and assigned incorrect rates to most clades in most trees.
      In empirical analyses, BAMM behaved as expected from simulations, and assigned
      different rates to clades when clades were analyzed alone versus across the tree
      (i.e., with rate heterogeneity). Rabosky recently criticized our paper, focusing
      primarily on the idea that our comparison of BAMM to another approach (method-of
      moments estimators of Magallon and Sanderson, or MS estimators) was unfair to
      BAMM. Here, we provide further evidence that BAMM gives misleading rate estimates
      in empirical studies. We then describe how Rabosky's rown method comparisons were
      either acknowledged as being problematic or were described inaccurately (to favor
      BAMM). Finally, we show that the MS estimators can perform well when rates vary
      over time, despite untested assertions that they require constant rates to be
      accurate. Many other methods are available for analyzing diversification rates:
      we argue that BAMM should be avoided for estimating both diversification rates
      and rate shifts.

PMID- 30101972
TI  - Enhancing partner support to improve smoking cessation.
AB  - BACKGROUND: While many cessation programmes are available to assist smokers in
      quitting, research suggests that support from individual partners, family
      members, or 'buddies' may encourage abstinence. OBJECTIVES: To determine if an
      intervention to enhance one-to-one partner support for smokers attempting to quit
      improves smoking cessation outcomes, compared with cessation interventions
      lacking a partner-support component. SEARCH METHODS: We limited the search to the
      Cochrane Tobacco Addiction Group Specialised Register, which was updated in April
      2018. This includes the results of searches of the Cochrane Central Register of
      Controlled Trials (CENTRAL); MEDLINE (via OVID); Embase (via OVID); and PsycINFO
      (via OVID). The search terms used were smoking (prevention, control, therapy),
      smoking cessation and support (family, marriage, spouse, partner, sexual partner,
      buddy, friend, cohabitant and co-worker). We also reviewed the bibliographies of
      all included articles for additional trials. SELECTION CRITERIA: We included
      randomised controlled trials recruiting people who smoked. Trials were eligible
      if they had at least one treatment arm that included a smoking cessation
      intervention with a partner-support component, compared to a control condition
      providing behavioural support of similar intensity, without a partner-support
      component. Trials were also required to report smoking cessation at six months
      follow-up or more. DATA COLLECTION AND ANALYSIS: Two review authors independently
      identified the included studies from the search results, and extracted data using
      a structured form. A third review author helped resolve discrepancies, in line
      with standard methodological procedures expected by Cochrane. Smoking abstinence,
      biochemically verified where possible, was the primary outcome measure and was
      extracted at two post-treatment intervals where possible: at six to nine months
      and at 12 months or longer. We used a random-effects model to pool risk ratios
      from each study and estimate a summary effect. MAIN RESULTS: Our update search
      identified 465 citations, which we assessed for eligibility. Three new studies
      met the criteria for inclusion, giving a total of 14 included studies (n = 3370).
      The definition of partner varied among the studies. We compared partner support
      versus control interventions at six- to nine-month follow-up and at 12 or more
      months follow-up. We also examined outcomes among three subgroups: interventions
      targeting relatives, friends or coworkers; interventions targeting spouses or
      cohabiting partners; and interventions targeting fellow cessation programme
      participants. All studies gave self-reported smoking cessation rates, with
      limited biochemical verification of abstinence. The pooled risk ratio (RR) for
      abstinence was 0.97 (95% confidence interval (CI) 0.83 to 1.14; 12 studies; 2818
      participants) at six to nine months, and 1.04 (95% CI 0.88 to 1.22; 7 studies;
      2573 participants) at 12 months or more post-treatment. Of the 11 studies that
      measured partner support at follow-up, only two reported a significant increase
      in partner support in the intervention groups. One of these studies reported a
      significant increase in partner support in the intervention group, but smokers'
      reports of partner support received did not differ significantly. We judged one
      of the included studies to be at high risk of selection bias, but a sensitivity
      analysis suggests that this did not have an impact on the results. There were
      also potential issues with detection bias due to a lack of validation of
      abstinence in five of the 14 studies; however, this is not apparent in the
      statistically homogeneous results across studies. Using the GRADE system we rated
      the overall quality of the evidence for the two primary outcomes as low. We
      downgraded due to the risk of bias, as we judged studies with a high weighting in
      analyses to be at a high risk of detection bias. In addition, a study in both
      analyses was insufficiently randomised. We also downgraded the quality of the
      evidence for indirectness, as very few studies provided any evidence that the
      interventions tested actually increased the amount of partner support received by
      participants in the relevant intervention group. AUTHORS' CONCLUSIONS:
      Interventions that aim to enhance partner support appear to have no impact on
      increasing long-term abstinence from smoking. However, most interventions that
      assessed partner support showed no evidence that the interventions actually
      achieved their aim and increased support from partners for smoking cessation.
      Future research should therefore focus on developing behavioural interventions
      that actually increase partner support, and test this in small-scale studies,
      before large trials assessing the impact on smoking cessation can be justified.

PMID- 30101973
TI  - Mindfulness, selfcompassion, and depressive symptoms in chronic pain: The role of
      pain acceptance.
AB  - OBJECTIVE(S): The aim of this study was to test a theory driven model in which
      pain acceptance (both pain willingness [PW] and activity engagement [AE])
      mediates the relationships of mindfulness and selfcompassion with depressive
      symptoms, while controlling for pain intensity. METHODS: A path analysis was
      conducted using AMOS software to test a meditational model in a sample of women
      with chronic musculoskeletal pain (N = 231). RESULTS: Participants with higher
      levels of mindful awareness and selfcompassion presented lower levels of pain
      intensity and depressive symptoms, and higher levels of AE. PW did not
      significantly correlate with any variable in study. The mediation analysis showed
      that AE mediated the relationship between selfcompassion and depressive symptoms,
      independently from pain intensity. CONCLUSIONS: These findings seem to
      corroborate the hypothesis that selfcompassion is rooted in a motivational
      system, as it seems to correlate with less depressive symptoms through increasing
      the engagement with valued actions despite experiencing pain.

PMID- 30101974
TI  - Childhood maltreatment and psychotic experiences: Exploring the specificity of
      early maladaptive schemas.
AB  - OBJECTIVE: One potential mechanism that has received limited attention in
      psychosis research is early maladaptive schemas (EMS). Our aim was to examine
      whether EMS acts as a potential mediating pathway between early trauma and
      psychotic symptomology. METHODS: A quantitative survey was conducted online. N =
      302 participants took part. The analysis used a multiple mediation framework.
      RESULTS: Analysis demonstrated significant specificity effects. Different forms
      of child maltreatment were significantly associated with psychosis experiences
      through specific dimensions of maladaptive schemas. CONCLUSIONS: Results
      indicated specificity effects in that specific types of maltreatment are
      associated with specific maladaptive schemas. From a practitioner's perspective,
      these findings offer credence to cognitive theories of psychopathology, and
      support the validity of EMS identification and modification among clients with
      psychotic symptomology both as a fundamental component of traditional CBT and
      within specialized schema-focused therapy.

PMID- 30101975
TI  - Bidirectional adaptive introgression between two ecologically divergent sparrow
      species.
AB  - Natural hybrid zones can be used to dissect the mechanisms driving key
      evolutionary processes by allowing us to identify genomic regions important for
      establishing reproductive isolation and that allow for transfer of adaptive
      variation. We leverage whole-genome data in a system where two bird species, the
      saltmarsh (Ammospiza caudacuta) and Nelson's (A. nelsoni) sparrow, hybridize
      despite their relatively high background genetic differentiation and past
      ecological divergence. Adaptive introgression is plausible in this system because
      Nelson's sparrows are recent colonists of saltwater marshes, compared to the
      specialized saltmarsh sparrow that has a longer history of saltmarsh adaptation.
      Comparisons among whole-genome sequences of 34 individuals from allopatric and
      sympatric populations show that ongoing gene flow is shaping the genomic
      landscape, with allopatric populations exhibiting genome-wide FST estimates close
      to double of that observed in sympatry. We characterized patterns of
      introgression across the genome and identify regions that exhibit biased
      introgression into hybrids from one parental species. These regions offer
      compelling candidates for genes related to tidal marsh adaptations suggesting
      that adaptive introgression may be an important consequence of hybridization.
      These findings highlight the value of considering the landscapes of both genome
      wide introgression and divergence when characterizing the evolutionary forces
      that drive speciation.

PMID- 30101976
TI  - Testing for latitudinal gradients in defense at the macroevolutionary scale.
AB  - Plant defenses against herbivores are predicted to evolve to be greater in warmer
      climates, such as lower latitudes where herbivore pressure is also thought to be
      higher. Instead, recent findings are often inconsistent with this expectation,
      suggesting alternative hypotheses are needed. We tested for latitudinal gradients
      in plant defense evolution at the macroevolutionary scale by characterizing plant
      chemical defenses across 80 species of the evening primroses, spanning both North
      and South America. We quantified phenolics in leaves, flowers, and fruits, using
      advanced analytical chemistry techniques. Dominant individual ellagitannin
      compounds, total concentrations of ellagitannins, flavonoids, total phenolics,
      and compound diversity were quantified. Variation in these compounds was
      predicted with latitude, temperature, precipitation, and continent using
      phylogenetic generalized least squares (PGLS) multiple regression models.
      Latitude did not strongly explain variation in chemical defenses. Instead, fruit
      total ellagitannins, oenothein A, and total phenolics were greater in species
      inhabiting regions with colder climates. Using analytical chemistry and 80
      species in two continents, we show that contrary to classic predictions,
      concentrations of secondary metabolites are not greater at lower latitudes or in
      warmer regions. We propose higher herbivore pressure in colder climates and
      gradients in resource availability as potential drivers of the observed patterns
      in Oenothera.

PMID- 30101978
TI  - Assessing the use of vibrations and strobe lights at fish screens as enhanced
      deterrents for two estuarine fishes.
AB  - The role of vision and the lateral-line system in fish-screen avoidance
      behaviours was investigated in shiner surfperch Cymatogaster aggregata and
      staghorn sculpin Leptocottus armatus. Avoidance experiments were conducted in
      front of water-diversion-type wedge-wire fish screens in a laboratory flume with
      a 0.3 m s-1 water velocity. Fish contacted the screens less frequently during the
      day than night, indicating that fish screen avoidance is visually mediated during
      the day. Input from the fishes' lateral-line systems was also blocked with
      streptomycin-sulphate treatments during the night to determine if these fishes
      use mechanoreceptive cues to guide screen avoidance in darkened conditions.
      Streptomycin-treated and untreated fish had similar contact rates suggesting that
      mechanoreceptive guidance was not increasing the fishes' abilities to avoid
      contact with non-vibrating screens at night. Fishes were stained with 2-(4
      (dimethylamino)styryl)-N-ethylpyridinium iodide (DASPEI) to assess the
      streptomycin treatment's effectiveness. We also tested the fishes' ability to
      avoid contact with the screens at night, when a strobe light or industrial
      vibrator was operated on the screens, to respectively increase the screen's
      visual and mechanoreceptory guidance potential. Cymatogaster aggregata contacted
      the screens significantly less frequently when they were vibrating, compared with
      their night-time controls, suggesting useful mechanoreceptive guidance.
      Leptocottus armatus contacted the screens significantly less frequently under
      strobe-light illumination, compared with their night-time controls, suggesting
      useful visual guidance. This research should benefit fishery and water-resource
      managers, regarding the development of future fish-protection decisions at
      screened water diversions.

PMID- 30101977
TI  - Using a Functional Carrot Powder Ingredient to Produce Sausages with High Levels
      of Nutraceuticals.
AB  - : In this study, a functional carrot powder (FCP) ingredient was obtained by
      applying wounding stress to carrot (shredding and storing for 48 hr at 15 
      degrees C) prior to dehydration (60  degrees C) and milling. Likewise, FCP was
      incorporated into sausage formulations, which were further characterized. The
      application of wounding stress in carrots resulted in a FCP with higher fiber
      (30.1%) and chlorogenic acid (798.4%) content as compared with control carrot
      powder (CCP). Likewise, FCP showed higher water (19%) and oil (3.9%) absorption
      capacity as compared with CCP. Sausage formulation with 4% (w/w) of FCP was
      characterized, further evaluated during storage (42 days, 4  degrees C), and
      compared with a formulation added with 4% (w/w) CCP. FCP and CCP formulations
      increased fiber of sausages by 72.7%, and fortified them with carotenoids,
      providing 30% to 40% of vitamin A daily requirements per portion (62.5 g). FCP
      did not affect purge loss, and sausages contained 270% and 377% more total
      phenolics and chlorogenic acid content as compared with CCP sausages. FCP
      formulation presented adequate sensory acceptability and its carotenoid and
      phenolic content remained stable during storage. Results indicated that FCP could
      be used as an ingredient in sausage formulation to increase the content of
      nutraceuticals without affecting its shelf-life. PRACTICAL APPLICATION: Wounding
      stress (by shredding) was applied to carrots prior to dehydration and milling to
      obtain a carrot powder with higher fiber and phenolic compounds as compared with
      control carrot powder (CCP). FCP showed higher water and oil absorption capacity
      than CCP. FCP addition to sausage formulations at 4% didn't affect purge loss,
      and resulted in sausages with higher phenolic compounds and dietary fiber.
      Furthermore, FCP formulations presented adequate sensory acceptability and its
      carotenoid and phenolic content remained stable during storage. FCP could be used
      as an ingredient in sausage formulation to increase the content of nutraceuticals
      without affecting its shelf-life.

PMID- 30101979
TI  - The importance of exercise intensity, volume and metabolic signalling events in
      the induction of mitochondrial biogenesis.

PMID- 30101980
TI  - Victims of war-Psychoendocrine evidence for the impact of traumatic stress on
      psychological well-being of adolescents growing up during the Israeli-Palestinian
      conflict.
AB  - Violent conflicts are severe traumatic stressors with detrimental effects on
      physical and mental health, with children and adolescents being particularly at
      risk. For the hypothalamic-pituitary-adrenal (HPA) axis, characteristic patterns
      of dysregulation in trauma-exposed individuals have been shown. This study set
      out to investigate self-reported mental well-being in Palestinian adolescents
      growing up during the Israeli-Palestinian conflict. Hair cortisol concentrations
      (HCC) as a psychoendocrine marker for long-term HPA axis aberrations along with
      the potential protective factor sense of coherence (SoC; i.e., the global mindset
      to interpret the world and emerging stressors as comprehensible, manageable, and
      meaningful) were examined. Between 2014 and 2016, posttraumatic stress disorder
      (PTSD), depression, anxiety, HCC, and SoC were examined in 233 adolescents aged
      11 to 16 from the West Bank. More than half of the participants reported trauma
      exposure, with 40% fulfilling the criteria of a preliminary PTSD diagnosis and a
      high prevalence of anxiety and depression. HCC was significantly elevated in the
      PTSD subgroup compared to the subgroup not exposed to any traumatic events (p =
      0.046), with trauma-exposed individuals in between. HCC was further associated
      with typical sequelae of traumatic stress. Notably, SoC was inversely related to
      self-reported psychopathology, as well as to HCC in the trauma group. The results
      illustrate the situation of adolescents exposed to chronic traumatic stress and
      extend the literature on aberrant HPA axis functioning under such conditions.
      They also point out a central role of SoC, which may imply new strategies to aid
      individuals exposed to ongoing conflicts.

PMID- 30101981
TI  - Novel Angiotensin-Converting Enzyme Inhibitory Peptides Derived from Oncorhynchus
      mykiss Nebulin: Virtual Screening and In Silico Molecular Docking Study.
AB  - : Excessive concentrations of angiotensin-converting enzyme (ACE) can give rise
      to high blood pressure, and is harmful to the body. ACE inhibitory peptides from
      food proteins are considered good sources of function food. However, the
      preparation of ACE inhibitory peptides by classical method faces many challenges.
      Three novel ACE inhibitory peptides were identified by in silico methods, and
      showed potent activity against ACE in vitro. The simulation hydrolysis of nebulin
      was performed with ExPASy PeptideCutter program. Potential activity, solubility,
      and absorption, distribution, metabolism, excretion, and toxicity properties of
      generated peptides were predicted using program online. Molecular docking
      displayed that EGF, HGR, and VDF were docked into the S1 and S2 pockets of ACE.
      Meanwhile, Phe and Arg at the C-terminal enhance ACE affinity. The IC50 values of
      EGF, HGR, and VDF were 474.65 +/- 0.08, 106.21 +/- 0.52, and 439.27 +/- 0.09 MUM,
      respectively. Three peptides EGF, HGR, and VDF from Oncorhynchus mykiss nebulin
      were identified, and the molecular mechanism between ACE and peptides was
      clarified using in silico methods. The results suggested that Oncorhynchus mykiss
      nebulin would be an attractive raw material of antihypertensive nutraceutical
      ingredients. PRACTICAL APPLICATION: This study has shown the potential of
      Oncorhynchus mykiss nebulin as good sources for producing ACE inhibitory
      peptides. According to this finding, in silico approach is the feasible way for
      prediction and identification of food-derived ACE inhibitory peptides in emerging
      nutraceutical field.

PMID- 30101983
TI  - Legacy of excess: consequences of maternal obesity for the adult offspring.

PMID- 30101982
TI  - Diverse Profiles of Biofilm and Adhesion Genes in Staphylococcus Aureus Food
      Strains Isolated from Sushi and Sashimi.
AB  - : Staphylococcus aureus is able to form multilayer biofilms embedded within a
      glycocalyx or slime layer. Biofilm formation poses food contamination risks and
      can subsequently increase the risk of food poisoning. Identification of food
      related S. aureus strains will provide additional data on staphylococcal food
      poisoning involved in biofilm formation. A total of 52 S. aureus strains isolated
      from sushi and sashimi was investigated to study their ability for biofilm
      formation using crystal violet staining. The presence of accessory gene regulator
      (agr) groups and 15 adhesion genes was screened and their associations in biofilm
      formation were studied. All 52 S. aureus strains showed biofilm production on the
      tested hydrophobic surface with 44% (23/52) strains classified as strong, 33%
      (17/52) as moderate, and 23% (12/52) as weak biofilm producers. The frequency of
      agr-positive strains was 71% (agr group 1 = 21 strains; agr group 2 = 2 strains;
      agr group 3 = 12 strains; agr group 4 = 2 strains) whereas agr-negative strains
      were 29% (15/52). Twelve adhesion genes were detected and 98% of the S. aureus
      strains carried at least one adhesion gene. The ebps was significantly (p < .05)
      associated with strong biofilm producing strains. In addition, eno, clfA, icaAD,
      sasG, fnbB, cna, and sasC were significantly higher in the agr-positive group
      compared to the agr-negative group. The results of this study suggest that the
      presence of ebps, eno, clfA, icaAD, sasG, fnbB, cna, and sasC may play an
      important role in enhancing the stage of biofilm-related infections and warrants
      further investigation. PRACTICAL APPLICATION: This work contributes to the
      knowledge on the biofilm formation and the distribution of agr groups in S.
      aureus strains as well as microbial surface components in recognizing adherence
      matrix molecules of organisms isolated from ready-to-eat sushi and sashimi. The
      findings provide valuable information to further study the roles of specific
      genes in causing biofilm-related infections.

PMID- 30101984
TI  - Task-free auditory EEG paradigm for probing multiple levels of speech processing
      in the brain.
AB  - While previous studies on language processing highlighted several ERP components
      in relation to specific stages of sound and speech processing, no study has yet
      combined them to obtain a comprehensive picture of language abilities in a single
      session. Here, we propose a novel task-free paradigm aimed at assessing multiple
      levels of speech processing by combining various speech and nonspeech sounds in
      an adaptation of a multifeature passive oddball design. We recorded EEG in
      healthy adult participants, who were presented with these sounds in the absence
      of sound-directed attention while being engaged in a primary visual task. This
      produced a range of responses indexing various levels of sound processing and
      language comprehension: (a) P1-N1 complex, indexing obligatory auditory
      processing; (b) P3-like dynamics associated with involuntary attention allocation
      for unusual sounds; (c) enhanced responses for native speech (as opposed to
      nonnative phonemes) from ~50 ms from phoneme onset, indicating phonological
      processing; (d) amplitude advantage for familiar real words as opposed to
      meaningless pseudowords, indexing automatic lexical access; (e) topographic
      distribution differences in the cortical activation of action verbs versus
      concrete nouns, likely linked with the processing of lexical semantics. These
      multiple indices of speech-sound processing were acquired in a single attention
      free setup that does not require any task or subject cooperation; subject to
      future research, the present protocol may potentially be developed into a useful
      tool for assessing the status of auditory and linguistic functions in
      uncooperative or unresponsive participants, including a range of clinical or
      developmental populations.

PMID- 30101985
TI  - Cortisol response to awakening in prepubertal children and adults: Magnitude and
      variability.
AB  - Within the first 30-45 min after awakening, there is a characteristic rise in
      cortisol that is referred to as cortisol awakening response (CAR). Over the past
      decades, the CAR has become an important biomarker, mainly because of its
      reported association with health and disease. Previous research showed that the
      CAR can already be reliably assessed in infants and children. Yet, earlier
      findings on the influence of age have been inconsistent, and limited attention
      has been devoted to prepubertal children. Here, we aimed to contrast the
      magnitude and stability of the CAR in prepubertal children and adults. To this
      end, 24 healthy adults between 35 and 50 years of age and 24 healthy children
      between 6 and 9 years of age collected four salivary cortisol samples within 45
      min after awakening on 4 separate days, 2 weekdays, and 2 weekend days. Our
      results showed that there was a marked CAR on weekdays and weekend days in both
      adults and children. In children, however, the CAR was overall significantly
      attenuated relative to adults. Moreover, while the cortisol increases after
      awakening were, both on weekdays and weekend days, highly correlated in adults,
      there were no such associations in children. Together, these data suggest that
      the CAR is less pronounced and less stable in prepubertal children compared to
      adults. Such age differences need to be taken into account when using the CAR as
      a biomarker in clinical settings.

PMID- 30101986
TI  - Massively parallel sequencing techniques for forensics: A review.
AB  - DNA sequencing, starting with Sanger's chain termination method in 1977 and
      evolving into the next generation sequencing (NGS) techniques of today that
      employ massively parallel sequencing (MPS), has become essential in application
      areas such as biotechnology, virology, and medical diagnostics. Reflected by the
      growing number of articles published over the last 2-3 years, these techniques
      have also gained attention in the forensic field. This review contains a brief
      description of first, second, and third generation sequencing techniques, and
      focuses on the recent developments in human DNA analysis applicable in the
      forensic field. Relevance to the forensic analysis is that besides generation of
      standard STR-profiles, DNA repeats can also be sequenced to look for
      polymorphisms. Furthermore, additional SNPs can be sequenced to acquire
      information on ancestry, paternity or phenotype. The current MPS systems are also
      very helpful in cases where only a limited amount of DNA or highly degraded DNA
      has been secured from a crime scene. If enough autosomal DNA is not present,
      mitochondrial DNA can be sequenced for maternal lineage analysis. These
      developments clearly demonstrate that the use of NGS will grow into an
      indispensable tool for forensic science.

PMID- 30101987
TI  - Global patterns of STR sequence variation: Sequencing the CEPH human genome
      diversity panel for 58 forensic STRs using the Illumina ForenSeq DNA Signature
      Prep Kit.
AB  - The 944 individuals of the CEPH human genome diversity panel (HGDP-CEPH), a
      standard sample set of 51 globally distributed populations, were sequenced using
      the Illumina ForenSeqTM DNA Signature Prep Kit. The ForenSeqTM system is a single
      multiplex for the MiSeq/FGxTM massively parallel sequencing instrument,
      comprising: amelogenin, 27 autosomal STRs, 24 Y-STRs, 7 X-STRs, and 94
      SNPforID+Kiddlab autosomal ID-SNPs (plus optionally detected ancestry and
      phenotyping SNP sets). We report in detail the patterns of sequence variation
      observed in the repeat regions of the 58 forensic STR loci typed by the
      ForenSeqTM system. Sequence alleles were characterized and repeat region
      structures annotated by aligning the ForenSeqTM sequence output to the latest
      GRCh38 human reference sequence, necessitating the reversal and re-alignment of
      STR allele sequences reported by the ForenseqTM system in 20 of 58 STRs (plus the
      reverse alleles in two Y-STRs with duplicated-inverted repeat regions).
      Individual population sample sizes of the HGDP-CEPH panel do not allow reliable
      inferences to be made about levels of genetic variability in low frequency STR
      alleles-where particular sequence variants are found in only a few individuals;
      but we assessed the occurrence of both population-specific sequence variants and
      singleton observations; finding each of these in a sizeable proportion of HGDP
      CEPH samples, with consequences for planning the co-ordinated compilation of
      sequence variation on a much larger scale than was required before by forensic
      laboratories now adopting massively parallel sequencing.

PMID- 30101988
TI  - Authors' Reply to the Commentary in the journal of Electrophoresis regarding "The
      effect of simulated space radiation on the N-glycosylation of human
      immunoglobulin G1" by J.J. Bevelacqua and S.M.J. Mortazavi.
AB  - By reading the commentary of Bevelacqua and Mortazavi regarding our recently
      published paper titled as "The effect of simulated space radiation on the N
      glycosylation of human immunoglobulin G1"[1], we are afraid that some of the
      important messaging aspects of our paper might not have been articulated
      adequately to be fully understandable for a wider audience, i.e., not separation
      scientists. First, we should clarify that complete space radiation description
      was not the goal of this paper. In this short communication we only intended to
      show the effect of simulated space radiation on the conserved N-glycosylation of
      IgG1 molecules with the goal to understand if they could be utilized as disease
      biomarkers during longer space missions, similar to that as they are currently
      used here on Earth, e.g. for autoimmune disease or aging markers. Therefore, no
      discussion was given about any biological effects either as our study only
      investigated the qualitative effects of proton irradiation on the N-linked
      carbohydrate decomposition of IgG type 1 molecules with the intent of suggesting
      them to be used as biomarkers during deep space travel. Radioadaptation was never
      an issue in our study for the reasons mentioned above.

PMID- 30101989
TI  - What is palliative care? Perceptions of healthcare professionals.
AB  - BACKGROUND: Despite increased attention and knowledge in palliative care, there
      is still confusion concerning how to interpret the concept of palliative care and
      implement it in practice. This can result in difficulties for healthcare
      professionals in identifying patients whom would benefit from palliative care,
      which, in turn, could lead to a delay in meeting patients' needs. AIM: To explore
      healthcare professionals' perceptions of palliative care. METHOD: Data were
      collected through twelve interprofessional focus group interviews in community
      care and hospital wards in south Sweden (n = 74). All interviews were analysed
      with latent content analysis. RESULTS: Three domains were revealed: first, a
      blurred conceptual understanding as participants described palliative care using
      synonyms, diagnoses, phases, natural care and holism; second, a challenge to
      communicate transitions concerned the importance of how and when the transition
      to palliative care was communicated and documented; finally, a need for
      interprofessional collaboration was described as well as the consequences for
      severely ill persons, relatives and healthcare professionals when it was not
      established. CONCLUSION: The perceptions about how to interpret palliative care
      differed as well as when palliative care should be offered and decided, which
      might have practical consequences. How long a person has left to live is of great
      significance for decision-making, caregiving and preparation in palliative care.
      The challenge is to use interprofessional communication to promote understanding
      and collaborate across varied care levels. Integrating palliative care across
      diverse care levels could be one way to reduce the ambiguity of palliative care.

PMID- 30101990
TI  - Gut microbiota alterations in moderate to severe acne vulgaris patients.
AB  - Acne vulgaris is a chronic inflammatory dermatosis affecting approximately 85% of
      adolescents. There are many factors contributing to the development of this
      ailment. A recent study indicated that gut microbiota takes part in the
      pathogenesis of acne. We aimed to investigate the link between acne vulgaris and
      gut microbiota. A total of 31 moderate to severe acne vulgaris patients and 31
      healthy controls were enrolled. We collected their feces, and gut microbiota was
      evaluated by the hypervariable regions of 16S rRNA genes through high-throughput
      sequencing. We identified links between acne vulgaris and changes of gut
      microbiota. At the phylum level, Actinobacteria (0.89% in acne patients and 2.84%
      in normal controls, P = 0.004) was decreased and Proteobacteria (8.35% in acne
      patients and 7.01% in normal controls, P = 0.031) was increased. At the genus
      level, Bifidobacterium, Butyricicoccus, Coprobacillus, Lactobacillus and
      Allobaculum were all decreased. The observed difference in genera between acne
      patients and healthy controls provides a new insight into the link between gut
      microbiota changes and acne vulgaris risk.

PMID- 30101991
TI  - Nutrition and Inflammatory Biomarkers in Chronic Pancreatitis Patients.
AB  - BACKGROUND: Chronic pancreatitis (CP) patients frequently experience
      malabsorption and maldigestion, leading to micronutrient and macronutrient
      deficiencies. Comorbid diabetes and lifestyle habits, such as alcohol
      consumption, may impact nutrition status. METHODS: We compared micronutrient
      antioxidant, bone metabolism, serum protein, and inflammatory marker levels in
      301 CP patients and 266 controls with no known pancreatic disease. We analyzed
      serum prealbumin and retinol binding protein; vitamins A, D, E, and B12;
      osteocalcin; tumor necrosis factor-alpha; and C-reactive protein (CRP). We also
      evaluated biomarkers among subsets of patients, examining factors including time
      since diagnosis, body mass index, alcohol as primary etiology, diabetes mellitus,
      vitamin supplementation, and pancreatic enzyme replacement. RESULTS: After
      correcting for multiple comparisons, CP patients had significantly lower levels
      than controls of the following: vitamin A (40.9 vs 45.4 MUg/dL) and vitamin E
      (alpha-tocopherol [8.7 vs 10.3 mg/L] and gamma-tocopherol [1.8 vs 2.2 mg/L]), as
      well as osteocalcin (7.9 vs 10 ng/mL) and serum prealbumin (23 vs 27 mg/dL). Both
      patients and controls who took vitamin supplements had higher serum levels of
      vitamins than those not taking supplements. Compared with controls, in controlled
      analyses, CP patients had significantly lower levels of vitamins A, D, and E
      (both alpha-tocopherol and gamma-tocopherol). CP patients also had significantly
      lower levels of osteocalcin, serum prealbumin, and retinol binding protein, and
      higher CRP. CONCLUSIONS: CP patients demonstrated lower levels of selected
      nutrition and bone metabolism biomarkers than controls. Diabetes and alcohol did
      not impact biomarkers. Vitamin supplements and pancreatic enzyme replacement
      therapy improved nutrition biomarkers in CP patients.

PMID- 30101992
TI  - Resveratrol promotes in vitro activation of ovine primordial follicles by
      reducing DNA damage and enhancing granulosa cell proliferation via
      phosphatidylinositol 3-kinase pathway.
AB  - We aimed to study the effects of resveratrol on the morphology, DNA
      fragmentation, follicular activation and cell proliferation after in vitro
      culture of ovine ovarian tissue, and to verify if PI3K pathway is involved in
      resveratrol action in the sheep ovary. Ovaries were collected and divided into
      fragments. One fragment was fixed for histology (fresh control). The remaining
      fragments were cultured for 7 days in control medium (alpha-MEM+ ) alone or with
      resveratrol (2, 10 or 30 uM). After culture, ovarian tissue was destined to
      morphological analysis. TUNEL and proliferating cell nuclear antigen (PCNA)
      analyses were performed in the fresh control, alpha-MEM+ and 2 uM resveratrol.
      Inhibition of PI3K activity was performed through pre-treatment with LY294002.
      The percentage of normal follicles was similar between alpha-MEM+ and 2 uM
      resveratrol, and higher than those in other resveratrol treatments. An increase
      in follicular activation was observed in all treatments compared to fresh
      control. DNA fragmentation decreased in tissues cultured in 2 uM resveratrol
      compared to alpha-MEM+ . Moreover, PCNA-positive cells were higher in 2 uM
      resveratrol than in alpha-MEM+ . LY294002 inhibited follicular activation
      stimulated by alpha-MEM+ and 2 uM resveratrol. In conclusion, 2 uM resveratrol
      promotes primordial follicle activation compared to the fresh control by reducing
      DNA fragmentation and stimulating granulosa cell proliferation through activation
      of the PI3K pathway.

PMID- 30101993
TI  - Vitamin D Status Is Associated With Development of Hospital-Acquired Pressure
      Injuries in Critically Ill Surgical Patients.
AB  - BACKGROUND: Hospital-acquired pressure injuries (HAPIs) typically develop
      following critical illness due to immobility and suboptimal perfusion. Vitamin D
      helps to maintain epithelial cell integrity, particularly at barrier sites such
      as skin. It is unclear whether vitamin D status is a modifiable risk factor for
      HAPIs in critically ill patients. Our goal was to investigate the relationship
      between admission 25-hydroxyvitamin D (25OHD) levels with the development of
      HAPIs in surgical intensive care unit (ICU) patients. METHODS: We performed a
      retrospective cohort study of patients admitted to surgical ICUs at a major
      teaching hospital in Boston, Massachusetts. To investigate the association of
      25OHD levels with subsequent development of HAPIs, we performed logistic
      regression analyses, controlling for body mass index, Nutrition Risk in the
      Critically Ill score, ICU length of stay, and cumulative ICU caloric or protein
      deficit. RESULTS: A total of 402 patients comprised our analytic cohort. Each
      unit increment in 25OHD was associated with 11% decreased odds of HAPIs (odds
      ratio [OR] 0.89; 95% CI 0.840.95). When vitamin D status was dichotomized,
      patients with 25OHD <20 ng/mL were >2 times as likely to develop HAPIs (OR 2.51;
      95% CI 1.065.97) compared with patients with 25OHD >20 ng/mL. CONCLUSION: In our
      cohort of critically ill surgical patients, vitamin D status at ICU admission was
      linked to subsequent development of HAPIs. Randomized, controlled trials are
      needed to assess whether optimizing 25OHD levels in the ICU can reduce the
      incidence of HAPIs and improve other clinically relevant outcomes in critically
      ill patients.

PMID- 30101995
TI  - Monozygotic twins with group C xeroderma pigmentosum due to a compound
      heterozygous mutation in XPC gene.

PMID- 30101994
TI  - Severe thiopurine-induced leukocytopenia and hair loss in Japanese patients with
      defective NUDT15 variant: Retrospective case-control study.
AB  - Azathioprine (AZA)-metabolizing enzyme gene polymorphism is strongly related to
      thiopurine-induced leukocytopenia, which has not been well recognized in
      dermatological practice. We tried to see whether NUDT15 gene polymorphism can be
      the most susceptible genetic factor for AZA toxicity and the gene screening is
      beneficial to avoid the adverse events of AZA for the treatment of skin diseases.
      A retrospective study was carried out on 15 adult Japanese patients who were
      treated with AZA. Gene polymorphism of thiopurine-metabolizing enzymes NUDT15
      R139C, ITPA 94C>A, TPMT*2, TPMT*3B and TPMT*3C was analyzed. The single
      nucleotide polymorphisms were prospectively investigated in eight patients who
      were considered to have received AZA treatments. Two NUDT15 R139C homozygous
      patients developed agranulocytosis, severe thrombocytopenia and massive hair
      loss. The gene screening prior to AZA treatment identified one heterozygote of
      NUDT15 R139C and ITPA 94C>A, and three heterozygotes of ITPA 94C>A or TMPT*3C.
      Although this study was a retrospective single-center case-control observational
      study that enrolled a small number of patients, NUDT15 R139C homozygosity is a
      genetic risk of thiopurine-induced potentially fetal hematological abnormalities.
      To avoid serious adverse events, gene screening of thiopurine-metabolizing
      enzymes, at least NUDT15 R139C, should be considered prior to administration in
      genetically predisposed populations, such as Japanese. We highlight that massive
      hair loss in the early period of the initiation of AZA would be a sign of
      impending severe myelotoxicity.

PMID- 30101996
TI  - Nutritional Risk Screening 2002 Cut-Off to Identify High-Risk Is a Good Predictor
      of ICU Mortality in Critically Ill Patients.
AB  - BACKGROUND: The Nutritional Risk Screening 2002 (NRS-2002) is a widely
      recommended nutrition risk indicator. Two cut-offs have been proposed for
      intensive care unit (ICU) patients to classify nutrition risk: >=3-<5, at risk
      and >=5, high risk. To date, no study has directly compared these cut-offs. The
      aim of this study is to compare the NRS-2002 ICU nutrition risk cut-offs as
      predictors of clinical outcomes including infections, ICU and hospital mortality,
      length of stay (LOS), duration of mechanical ventilation (MVd), weaning failure,
      tracheotomy for prolonged MVd, and chronic critical illness (CCI). METHODS: Adult
      patients were screened and stratified according to NRS-2002 ICU criteria.
      Clinical, epidemiologic, and nutrition data were extracted from medical records.
      Statistical analysis for independent samples and Poisson regression were
      performed. RESULTS: A total of 185 patients were screened: 1 (0.54%) no risk; 96
      (51.89%) at risk, and 88 (47.56%) high risk. High-risk patients were older, had
      higher Simplified Acute Physiology Score 3 (62.0 +/- 14.1 vs 53.0 +/- 12.9,
      respectively; P < .001) and Sequential Organ Failure Assessment (6.9 +/- 3.7 vs
      5.1 +/- 3.1, respectively; P < .001), and developed more infections (42 [47.8%]
      vs 27 [28.1%]; P = .010). No differences were found for ICU and hospital LOS, MVd
      days, weaning failure, tracheotomy, and CCI. ICU and hospital mortality were
      higher in high-risk patients. The high-risk cut-off was predictor of ICU
      mortality (relative risk 2.10, 95% confidence interval 1.07-4.14; P = .032).
      CONCLUSION: Our data suggest that the NRS-2002 high-risk cut-off is associated
      with worse clinical outcomes and is a predictor for ICU mortality.

PMID- 30101997
TI  - Sharp-Tipped Zinc Nanowires as an Efficient Electrocatalyst for Carbon Dioxide
      Reduction.
AB  - Electrochemical carbon dioxide reduction is a key reaction for carbon dioxide
      conversion to valuable fuels and chemicals. Due to the intrinsic stability of the
      carbon dioxide molecule, a catalyst is required to minimize the energy input and
      improve the reaction rates. Although the developed catalysts still suffer from
      low catalytic activity, selectivity, and stability, these could be enhanced by
      the involvement of sharp tip structure. Here, we report a nanowire-like zinc
      electrocatalyst with sharp tips for carbon dioxide reduction. The catalyst
      achieves a geometry current density of -40 mA cm-2 at a potential of -0.95 V
      versus reversible hydrogen electrode over 35 hours with a stable carbon monoxide
      Faradaic efficiency of 98+/-2 %. The carbon monoxide partial current density
      surpasses by 60 % of that of the best reported zinc catalyst.

PMID- 30101998
TI  - Can the Bayley Scales of Infant Development at 18 months predict child behaviour
      at 7 years?
AB  - AIM: Infants born preterm (<37 weeks' gestation) are at risk of poor
      neurodevelopmental outcomes; hence, many neonatal centres routinely follow up
      infants using the Bayley Scales of Infant Development (BSID), although the
      predictive validity of the BSID for children born preterm is questionable. Our
      objective is to evaluate the predictive capacity of the BSID for behavioural
      functioning at school age of children born preterm. METHODS: Children (n = 657
      children born <33 weeks' gestation) were enrolled at birth from five neonatal
      centres around Australia. A psychologist assessed child development at 18 months
      using the BSID-II. When children were 7 years (corrected age) of age, parents
      completed the Strengths and Difficulties Questionnaire, the Behavior Rating
      Inventory of Executive Function and the Conners 3rd Edition Attention Deficit
      Hyperactivity Disorder Index. We explored associations between BSID-II at 18
      months and behaviour scores at 7 years and examined the interaction effect of the
      use of an allied health service between the BSID-II and behaviour assessments.
      RESULTS: For every one-point increase on the BSID-II Mental Development Index,
      behaviour scores decreased by 0.07 points for the Strengths and Difficulties
      Questionnaire Total Difficulties (95% confidence interval (CI) -0.10, -0.03),
      0.12 points for the Behavior Rating Inventory of Executive Function Global
      Executive Composite (95% CI -0.21, -0.04) and 0.16 points for the Conners 3rd
      Edition Attention Deficit Hyperactivity Disorder Index (95% CI -0.26, -0.05).
      CONCLUSION: The BSID-II at 18 months was weakly associated with parent-reported
      behaviour at 7 years in children born preterm.

PMID- 30101999
TI  - Waveguide effects and implications for cardiac magnetic resonance elastography: A
      finite element study.
AB  - Magnetic resonance elastography (MRE) is increasingly being applied to thin or
      small structures in which wave propagation is dominated by waveguide effects,
      which can substantially bias stiffness results with common processing approaches.
      The purpose of this work was to investigate the importance of such biases and
      artifacts on MRE inversion results in: (i) various idealized 2D and 3D geometries
      with one or more dimensions that are small relative to the shear wavelength; and
      (ii) a realistic cardiac geometry. Finite element models were created using
      simple 2D geometries as well as a simplified and a realistic 3D cardiac geometry,
      and simulated displacements acquired by MRE from harmonic excitations from 60 to
      220 Hz across a range of frequencies. The displacement wave fields were inverted
      with direct inversion of the Helmholtz equation with and without the application
      of bandpass filtering and/or the curl operator to the displacement field. In all
      geometries considered, and at all frequencies considered, strong biases and
      artifacts were present in inversion results when the curl operator was not
      applied. Bandpass filtering without the curl was not sufficient to yield accurate
      recovery. In the 3D geometries, strong biases and artifacts were present in 2D
      inversions even when the curl was applied, while only 3D inversions with
      application of the curl yielded accurate recovery of the complex shear modulus.
      These results establish that taking the curl of the wave field and performing a
      full 3D inversion are both necessary steps for accurate estimation of the shear
      modulus both in simple thin-walled or small structures and in a realistic cardiac
      geometry when using simple inversions that neglect the hydrostatic pressure term.
      In practice, sufficient wave amplitude, signal-to-noise ratio, and resolution
      will be required to achieve accurate results.

PMID- 30102000
TI  - Detection of dsDNA with [1,3]Dioxolo[4,5-f]benzodioxol (DBD) Dyes.
AB  - DBD fluorescent dyes have proven to be useful in numerous applications. To widen
      the range of biological applications, we propose three different types of DBD
      molecules that have been modified in such a way that DNA interaction becomes
      probable. After the successful synthesis of all three compounds, we tested their
      fluorescent properties and their DNA binding abilities. Two of the three probes
      exhibit an interaction with dsDNA with subsequent fluorescence enhancement. The
      determined binding constants of the two new DNA dyes are comparable to other
      minor-groove-binding dyes. Their large Stokes shifts and their long fluorescent
      lifetimes are outstanding features of these dyes.

PMID- 30102002
TI  - Dexmedetomidine attenuates lipopolysaccharide induced acute lung injury by
      targeting NLRP3 via miR-381.
AB  - Dexmedetomidine (Dex) is an agonist of alpha2-adrenergic receptors, and it is
      used as an anxiety reducing, sedative, and pain medication in clinical. Studies
      have shown that dexmedetomidine protects against lipopolysaccharide (LPS)-induced
      acute lung injury; however, the underlying mechanism is still unclear. To
      investigate, an acute lung injury mouse model was induced by intraperitoneal
      injection of LPS. Histopathological changes were determined by hematoxylin and
      eosin staining. Enzyme-linked immunosorbent assay was used to detect cytokines in
      serum. microRNA expression levels were detected by quantitative reverse
      transcription polymerase chain reaction. Protein levels were detected by western
      blot. Dex treatment significantly attenuated lung injury and inhibited the
      expression levels of the inflammation factors via reducing the level of NACHT,
      LRR, and PYD domains-containing protein 3 (NLRP3) and autocleavage of caspase-1.
      Moreover, mmu-miR-381, which targets the mRNA of NLRP3, was upregulated after Dex
      treatment. Dex attenuates LPS-induced acute lung injury via miR-381-targeted
      NLRP3.

PMID- 30102001
TI  - Synthesis of a Dimeric Base-Stabilized Cobaltosilylene Complex for Catalytic C-H
      Bond Functionalization and C-C Bond Formation.
AB  - The synthesis of a dimeric base-stabilized cobaltosilylene complex and its
      catalytic reactions are described. Treatment of the amidinato silicon(I) dimer
      [LSi:]2 (1; L=PhC(NtBu)2 ) with CoBr2 in toluene for 10 days afforded the dimeric
      amidinato cobaltosilylene [(LSi)MU-{CoBr(LSiBr)}]2 (2), which is speculated to
      proceed via "LSiCoBr" and "LSiBr" intermediates in the reaction. Compound 2 is
      paramagnetic, with an effective magnetic moment of 2.8 MUB. Its electronic
      structure was elucidated by single-crystal X-ray crystallography and DFT studies.
      It was capable of catalyzing C-H bond functionalization, in which a combination
      of 2, phosphine and MeMgI can regio- and stereoselectively promoted the addition
      of the C=C triple bonds in alkynes to the ortho-C-H position in arylpyridines. In
      addition, compound 2 catalyzed Kumada-type coupling reactions between aryl
      chlorides and the Grignard reagent 2-mesitylmagnesium bromide.

PMID- 30102003
TI  - Spinal Cord Atrophy in Multiple Sclerosis: A Systematic Review and Meta-Analysis.
AB  - BACKGROUND AND PURPOSE: Spinal cord atrophy (SCA) is an important emerging
      outcome measure in multiple sclerosis (MS); however, there is limited consensus
      on the magnitude and rate of atrophy. The objective of this study was to
      synthesize the available data on measures of SCA in MS. METHODS: Using published
      guidelines, relevant literature databases were searched between 1977 and 2017 for
      case-control or cohort studies reporting a quantitative measure of SCA in MS
      patients. Random-effects models pooled cross-sectional measures and longitudinal
      rates of SCA in MS and healthy controls (HCs). Student's t-test assessed
      differences between pooled measures in patient subgroups. Heterogeneity was
      assessed using DerSimonian and Laird's Q-test and the I 2 -index. RESULTS: A
      total of 1,465 studies were retrieved including 94 that met inclusion and
      exclusion criteria. Pooled estimates of mean cervical spinal cord (SC) cross
      sectional area (CSA) in all MS patients, relapsing-remitting MS (RRMS), all
      progressive MS, secondary progressive MS (SPMS), primary-progressive MS (PPMS),
      and HC were: 73.07 mm2 (95% CI [71.52-74.62]), 78.88 mm2 (95% CI [76.92-80.85]),
      69.72 mm2 (95% CI [67.96-71.48]), 68.55 mm2 (95% CI [65.43-71.66]), 70.98 mm2
      (95% CI [68.78-73.19]), and 80.87 mm2 (95% C I [78.70-83.04]), respectively.
      Pooled SC-CSA was greater in HC versus MS (P < .001) and RRMS versus progressive
      MS (P < .001). SCA showed moderate correlations with global disability in cross
      sectional studies (r-value with disability score range [-.75 to -.22]). In
      longitudinal studies, the pooled annual rate of SCA was 1.78%/year (95%CI [1.28
      2.27]). CONCLUSIONS: The SC is atrophied in MS. The magnitude of SCA is greater
      in progressive versus relapsing forms and correlates with clinical disability.
      The pooled estimate of annual rate of SCA is greater than reported rates of brain
      atrophy in MS. These results demonstrate that SCA is highly relevant as an
      imaging outcome in MS clinical trials.

PMID- 30102005
TI  - Minute Additions of DMSO Affect Protein Dynamics Measurements by NMR Relaxation
      Experiments through Significant Changes in Solvent Viscosity.
AB  - Studies of protein-ligand binding often rely on dissolving the ligand in dimethyl
      sulfoxide (DMSO) to achieve sufficient solubility, and then titrating the ligand
      solution into the protein solution. As a result, the final protein-ligand
      solution contains small amounts of DMSO in the buffer. Here we report how the
      addition of DMSO impacts studies of protein conformational dynamics. We used 15 N
      NMR relaxation to compare the rotational diffusion correlation time (tauC ) of
      proteins in aqueous buffer with and without DMSO. We found that tauC scales with
      the viscosity of the water-DMSO mixture, which depends sensitively on the amount
      of DMSO and varies by a factor of 2 across the relevant concentration range. NMR
      relaxation studies of side chains dynamics are commonly interpreted using tauC as
      a fixed parameter, obtained from backbone 15 N relaxation data acquired on a
      separate sample. Model-free calculations show that errors in tauC , arising from
      mismatched DMSO concentration between samples, lead to significant errors in
      order parameters. Our results highlight the importance of determining tauC for
      each sample or carefully matching the DMSO concentrations between samples.

PMID- 30102004
TI  - Sequential Transformation of Zirconium(IV)-MOFs into Heterobimetallic MOFs
      Bearing Magnetic Anisotropic Cobalt(II) Centers.
AB  - Heterometallic metal-organic frameworks (MOFs) allow the precise placement of
      various metals at atomic precision within a porous framework. This new level of
      control by MOFs promises fascinating advances in basic science and application.
      However, the rational design and synthesis of heterometallic MOFs remains a
      challenge due to the complexity of the heterometallic systems. Herein, we show
      that bimetallic MOFs with MX2 (INA)4 moieties (INA=isonicotinate; M=Co2+ or Fe2+
      ; X=OH- , Cl- , Br- , I- , NCS- , or NCSe- ) can be generated by the sequential
      modification of a Zr-based MOF. This multi-step modification not only replaced
      the linear organic linker with a square planar MX2 (INA)4 unit, but also altered
      the symmetry, unit cell, and topology of the parent structure. Single-crystal to
      single-crystal transformation is realized so that snapshots for transition
      process were captured by successive single-crystal X-ray diffraction.
      Furthermore, the installation of Co(NCS)2 (INA)4 endows field-induced slow
      magnetic relaxation property to the diamagnetic Zr-MOF.

PMID- 30102006
TI  - Dietary Supplementation with Nondigestible Oligosaccharides Reduces Allergic
      Symptoms and Supports Low Dose Oral Immunotherapy in a Peanut Allergy Mouse
      Model.
AB  - SCOPE: A major downside of oral immunotherapy (OIT) for food allergy is the risk
      of severe side effects. Non-digestible short- and long-chain fructo
      oligosaccharides (scFOS/lcFOS) reduce allergy development in murine models.
      Therefore, it is hypothesized that scFOS/lcFOS can also support the efficacy of
      OIT in a peanut allergy model. METHODS AND RESULTS: After sensitization to peanut
      extract (PE) using cholera toxin, C3H/HeOuJ mice are fed a 1% scFOS/lcFOS or
      control diet and receive OIT (1.5 or 15 mg PE). Hereafter, mice are exposed to PE
      via different routes to determine the safety and efficacy of treatment in
      clinical outcomes, PE-specific antibody production, and numbers of various immune
      cells. scFOS/lcFOS increases short-chain fatty acid levels in the caecum and
      reduce the acute allergic skin response and drop in body temperature after PE
      exposure. Interestingly, 15 mg and 1.5 mg OIT with scFOS/lcFOS induce protection
      against anaphylaxis, whereas 1.5 mg OIT alone does not. OIT, with or without
      scFOS/lcFOS, induces PE-specific immunoglobulin (Ig) IgG and IgA levels and
      increases CD103+ dendritic cells in the mesenteric lymph nodes. CONCLUSIONS:
      scFOS/lcFOS and scFOS/lcFOS combined with low dose OIT are able to protect
      against a peanut-allergic anaphylactic response.

PMID- 30102007
TI  - Selective Hydroarylation of 1,3-Diynes Using a Dimeric Manganese Catalyst:
      Modular Synthesis of Z-Enynes.
AB  - The transition-metal-catalyzed selective hydroarylation of unsymmetrical alkynes
      represents the state-of-art in organic chemistry, and still mainly relies on the
      use of precious late-transition-metal catalysts. Reported herein is an
      unprecedented MnI -catalyzed hydroarylation of unsymmetrical 1,3-diyne alcohols
      with commercially available arylboronic acids with predictive selectivity. This
      method addresses the challenges in regio-, stereo-, and chemoselectivity. It
      offers a general, convenient and practical strategy for the modular synthesis of
      multisubstituted Z-configurated conjugated enynes. This protocol is distinguished
      by its operational simplicity, complete selectivity, excellent functional-group
      compatibility, and gram-scale potential. A dimeric MnI species, Mn2 (CO)8 Br2 ,
      was proven to be a much more efficient catalyst precursor than Mn(CO)5 Br.

PMID- 30102009
TI  - Impact of tumour profiling on clinical trials in salivary gland cancer.

PMID- 30102010
TI  - Hydrogenation of CO2 -Derived Carbonates and Polycarbonates to Methanol and Diols
      by Metal-Ligand Cooperative Manganese Catalysis.
AB  - The first base-metal-catalysed hydrogenation of CO2 -derived carbonates to
      alcohols is presented. The reaction proceeds under mild conditions in the
      presence of a well-defined manganese complex with a loading as low as 0.25 mol %.
      The non-precious-metal homogenous catalytic system provides an indirect route for
      the conversion of CO2 into methanol with the co-production of value-added
      (vicinal) diols in yields of up to 99 %. Experimental and computational studies
      indicate a metal-ligand cooperative catalysis mechanism.

PMID- 30102011
TI  - MRI Findings and Outcomes in Patients Undergoing Microvascular Decompression for
      Glossopharyngeal Neuralgia.
AB  - BACKGROUND AND PURPOSE: Glossopharyngeal neuralgia causes extreme paroxysmal pain
      in the posterior pharynx, tonsillar region, base of tongue, or deep ear, that is,
      the distribution of the glossopharyngeal nerve. Some cases of glossopharyngeal
      neuralgia are associated with neurovascular conflict, usually by the posterior
      inferior cerebellar artery. Such symptomatic compression occurs only in proximal,
      centrally myelinated portions of the glossopharyngeal nerve near the brainstem.
      Microvascular decompression provides effective and durable pain relief for
      properly selected patients with medically refractory glossopharyngeal neuralgia.
      The purpose of this study is to describe a tailored MRI evaluation of
      neurovascular conflict in glossopharyngeal neuralgia to improve candidate
      selection for microvascular decompression. METHODS: Our team developed a
      glossopharyngeal neuralgia imaging and evaluation protocol including a grading
      system for neurovascular conflict of the glossopharyngeal nerve and applied it to
      evaluate candidates for microvascular decompression. RESULTS: Our team grades
      neurovascular conflict as "contact" (vessel touching nerve without intervening
      cerebrospinal fluid) versus "deformation" (deviation or distortion of nerve from
      its normal course by the offending vessel). MRIs of patients with
      glossopharyngeal neuralgia demonstrate proximal neurovascular conflict.
      Postoperative MRI demonstrates separation of the glossopharyngeal nerve from the
      offending vessel. CONCLUSION: A tailored glossopharyngeal neuralgia imaging
      evaluation protocol is presented. We believe this approach has helped improve
      microvascular decompression outcomes and reduce unnecessary procedures at our
      institution. Further research may elucidate whether clinical and imaging
      features, including neurovascular conflict severity, predict surgical outcome for
      glossopharyngeal neuralgia.

PMID- 30102008
TI  - The role of K63-linked polyubiquitination in cardiac hypertrophy.
AB  - Ubiquitination, also known as ubiquitylation, is a vital post-translational
      modification of proteins that play a crucial role in the multiple biological
      processes including cell growth, proliferation and apoptosis. K63-linked
      ubiquitination is one of the vital post-translational modifications of proteins
      that are involved in the activation of protein kinases and protein trafficking
      during cell survival and proliferation. It also contributes to the development of
      various disorders including cancer, neurodegeneration and cardiac hypertrophy. In
      this review, we summarize the role of K63-linked ubiquitination signalling in
      protein kinase activation and its implications in cardiac hypertrophy. We have
      also provided our perspectives on therapeutically targeting K63-linked
      ubiquitination in downstream effector molecules of growth factor receptors for
      the treatment of cardiac hypertrophy.

PMID- 30102012
TI  - RNA Structure and Cellular Applications of Fluorescent Light-Up Aptamers.
AB  - The cellular functions of RNA are not limited to their role as blueprints for
      protein synthesis. In particular, noncoding RNA, such as, snRNAs, lncRNAs,
      miRNAs, play important roles. With increasing numbers of RNAs being identified,
      it is well known that the transcriptome outnumbers the proteome by far. This
      emphasizes the great importance of functional RNA characterization and the need
      to further develop tools for these investigations, many of which are still in
      their infancy. Fluorescent light-up aptamers (FLAPs) are RNA sequences that can
      bind nontoxic, cell-permeable small-molecule fluorogens and enhance their
      fluorescence over many orders of magnitude upon binding. FLAPs can be encoded on
      the DNA level using standard molecular biology tools and are subsequently
      transcribed into RNA by the cellular machinery, so that they can be used as
      fluorescent RNA tags (FLAP-tags). In this Minireview, we give a brief overview of
      the fluorogens that have been developed and their binding RNA aptamers, with a
      special focus on published crystal structures. A summary of current and future
      cellular FLAP applications with an emphasis on the study of RNA-RNA and RNA
      protein interactions using split-FLAP and Forster resonance energy transfer
      (FRET) systems is given.

PMID- 30102013
TI  - Do the microorganisms from laboratory culture spent growth medium affect house
      dust mite fitness and microbiome composition?
AB  - The interaction of house dust mites (HDM) and microorganisms is the key factor in
      the survival of these mites in human-made environments. Spent growth medium
      (SPGM) provides the rest of the diet, along with dead mite bodies and
      microorganisms. SPGM represents a source of microorganisms for the recolonization
      of mite food and the mite digestive tract. An experiment was performed to observe
      how adding SPGM to the HDM diet affects HDM population growth, the microbiome
      composition and the microbial respiration in microcosms. We analyzed American
      house dust mite (Dermatophagoides farinae) and European house dust mite
      (Dermatophagoides pteronyssinus) originating from control diets and diets treated
      with an extract of SPGM from 1- and 3-month-old mite cultures. The microbiome was
      described using 16S and 18S barcode sequencing. The composition of the bacterial
      and fungal microbiomes differed between the HDM species, but the SPGM treatment
      influenced only the bacterial profile of D. farinae. In the D. farinae microbiome
      of specimens on SPGM-treated diets compared to those of the control situation,
      the Lactobacillus profile decreased, while the Cardinium, Staphylococcus,
      Acinetobacter, and Sphingomonas profiles increased. The addition of SPGM extract
      decreased the microbial respiration in the microcosms with and without mites in
      almost all cases. Adding SPGM did not influence the population growth of D.
      farinae, but it had a variable effect on D. pteronyssinus. The results indicated
      that the HDM are marginally influenced by the microorganisms in their feces.

PMID- 30102016
TI  - Reproductive Coercion and Women's Health.
AB  - Given the epidemic proportion of those affected, the impact of gender-based
      violence looms large in the study of women's health. One increasingly recognized
      facet of such violence is reproductive coercion, defined as behavior that
      interferes with autonomous decision-making in areas of reproductive health.
      Although the body of literature illustrating the pathology of reproductive
      coercion is limited, growing data on harms to reproductive choice, health
      outcomes, and future pregnancies are a sobering appeal for greater publicity and
      information. This review explores existing knowledge regarding reproductive
      coercion, highlights areas of future study, and underscores how women's health
      care providers can better serve this population.

PMID- 30102015
TI  - Spontaneous hemoperitoneum and anaphylactic shock associated with Hymenoptera
      envenomation in a dog.
AB  - OBJECTIVE: To describe the clinical presentation of a dog with spontaneous
      hemoperitoneum associated with anaphylactic shock from Hymenoptera envenomation.
      CASE SUMMARY: An 8-year-old female neutered Beagle presented as an emergency for
      acute onset of collapse, hematemesis, and hematochezia. The dog was tachycardic,
      tachypneic, and hypotensive. Initial assessment revealed a hemoperitoneum with
      documentation of a nonclotting sanguineous peritoneal effusion with PCV 81% and
      total protein concentration 65 g/L (6.5 g/dL). No obvious masses were appreciated
      ultrasonographically during original presentation and cytology of the peritoneal
      effusion was unremarkable. Peripheral PCV was 67% and total plasma protein
      concentration was 72 g/L (7.2 g/dL). A bee stinger was located in the right upper
      lip after presentation and was postulated to be the inciting trigger for the
      abdominal hemorrhage and shock. The patient was medically stabilized and
      ultimately made an uneventful recovery. Abdominal ultrasound performed 3 days
      after discharge revealed a single 0.85 cm hyperechoic liver nodule. Follow-up
      evaluation at 6 and 18 months after presentation documented a normal physical
      examination, unremarkable thoracic radiographs, and no change in the original
      hyperechoic liver nodule. NEW OR UNIQUE INFORMATION PROVIDED: This report details
      an unusual clinical presentation of anaphylactic shock due to Hymenoptera
      envenomation in a dog. To the authors' knowledge, spontaneous hemoperitoneum
      associated with anaphylaxis and bee envenomation has not been documented in the
      veterinary literature.

PMID- 30102017
TI  - Recent Advances in Earth-Abundant Photocathodes for Photoelectrochemical Water
      Splitting.
AB  - The conversion of solar energy into hydrogen through photoelectrochemical (PEC)
      water splitting is an attractive way to store renewable energy. Despite the
      intriguing concept of solar hydrogen production, efficient PEC devices based on
      earth-abundant semiconductors should be realized to compete economically with
      conventional steam reforming processes. Herein, recent milestones in photocathode
      development for PEC water splitting, particularly in earth-abundant
      semiconductors, in terms of new techniques for enhancing performance, as well as
      theoretical aspects, are highlighted. In addition, recent research into newly
      emerging low-cost p-type semiconductors in the PEC field, such as Cu2 BaSn(S,Se)4
      and Sb2 Se3 , are scrutinized and the advantages and disadvantages of each
      material assessed.

PMID- 30102014
TI  - A polymorphism rs3746444 within the pre-miR-499 alters the maturation of miR-499
      5p and its antiapoptotic function.
AB  - microRNAs (miRNAs) are non-coding RNAs that function as post-transcriptional
      regulators of cardiac development and cardiovascular diseases. Single nucleotide
      polymorphisms (SNPs) in miRNA genes are a novel class of genetic variations in
      the human genome that confer the risk of cardiovascular diseases. Here, we
      identified a polymorphism A->G (rs3746444) in miR-499 precursor (pre-miR-499)
      that affects the maturation of miR-499-5p and alters its antiapoptotic function
      by converting stable A-U base pair to wobble G-U base pair in pre-miR-499
      secondary structure. Furthermore, our results showed that the concentrations of
      plasma miR-499-5p could be correlated with myocardial infarction (MI) and heart
      failure (HF) patients in comparison with control subjects and polymorphism
      rs3746444 in miR-499 could influence its abundance in plasma. Finally, our
      results also showed that the variant of polymorphism in miR-499 influenced the
      severity of the myocardial infarction significantly. This is the first report to
      highlight the biological significance of this polymorphism on the maturation of
      miR-499-5p and its antiapoptotic role during MI. These findings may pave a way to
      better understand the individual variability based on miRNA SNPs in heart
      diseases and may contribute to better treatment for disease severity on a
      personalized level.

PMID- 30102018
TI  - Effectiveness of a comprehensive educational programme for Accredited Social
      Health Activists (ASHAs) to identify individuals in the Udupi district with
      bleeding disorders: A community-based survey.
AB  - INTRODUCTION: The awareness and knowledge on bleeding disorders is generally poor
      among the rural population. Accredited Social Health Activists (ASHAs) serve as
      the facilitators between the rural community and the health care system. Training
      of ASHAs in screening of rural population for early identification of bleeding
      disorders can enable prompt referral, timely detection and management of bleeding
      disorders. AIM: The aim of the study was to evaluate the effectiveness of an ASHA
      training programme for identification of suspected bleeding disorder cases.
      METHODS: A population-based, cross-sectional survey was implemented by 586
      Accredited Social Health Activists (ASHAs) in rural Udupi district, who underwent
      a structured training programme on identification of bleeding disorders. A survey
      record book with a screening tool on assessment of bleeding symptoms was given to
      each ASHA. The screening tool consisted of symptoms related to bleeding disorders
      and family history of bleeding disorders. Using the screening tool, ASHAs carried
      out a door-to-door survey. After screening, those who reported with bleeding
      symptoms were referred by the ASHAs to the investigator, who conducted further
      assessment. A detailed bleeding history was documented and bleeding symptom
      assessment was carried out using bleeding assessment tool (BAT) at the
      haemophilia treatment centre. Further coagulation assessments were carried out as
      per the treatment centre protocol. This paper highlights the evaluation of an
      ASHA training programme on identification of individuals with bleeding symptoms
      in the rural population. RESULTS: A total of 586 trained ASHAs surveyed a
      population of 318 214 in rural Udupi district. Out of the 124 cases reported by
      ASHAs, 29 bleeding disorder cases were identified; haemophilia (A and B) was the
      most commonly found bleeding disorder 22 (75.8%), followed by von Willebrand
      disease (vWD) 3 (10.3%) and 4 (13.8%) immune-mediated thrombocytopenic purpura
      (ITP), with an overall prevalence of 2.2/10 000 population. CONCLUSION: Training
      ASHA health care workers, who are the most important link between the community
      and health services, resulted in increased awareness among the public for the
      early detection of bleeding disorders.

PMID- 30102020
TI  - Bioinspired Load-Bearing Hydrogel Based on Engineered Sea Anemone Skin-Derived
      Collagen-Like Protein.
AB  - With the help of recombinant DNA technology, many protein candidates have been
      investigated and engineered for biomaterial applications. Particularly, several
      repeat sequences with unique secondary structures have been selected as minimal
      building blocks for biosynthesis to improve the mechanical properties of
      biomaterials. However, most of these structural proteins have been limited to
      silk, elastin, collagen, and resilin for decades. In the present work, new repeat
      sequence found in sea anemone are characterized and biosynthesized into a
      recombinant protein (named anegen) for potential use as a load-bearing
      biomaterial. Because its repeat sequence unit has a unique polyproline II
      structure, which is prevalently found in the triple-helix of collagen, it is
      assumed to be a promising structural protein candidate that can provide
      conformational flexibility and elasticity. Because anegen has ~10% tyrosine
      residues, inspiration is taken from di-tyrosine crosslinking in the hinge
      structures of insects, which can be initiated by light activation. It is found
      that the anegen hydrogel shows higher mechanical properties than a gelatin
      hydrogel and endures a compression series without deformation. Moreover, the
      mechanical properties of the anegen hydrogel are controllable through different
      crosslinking conditions in a wide range of material applications. Importantly,
      the anegen hydrogel exhibited suitable cell retainability and cell morphology as
      an implantable biomaterial. Thus, based on its mechanical properties and
      biocompatibility, the anegen hydrogel can be used as a potential load-bearing and
      cell-loading scaffolding biomaterial in the tissue and biomedical engineering
      fields.

PMID- 30102019
TI  - Utility of CT imaging in a novel form of high-dose-rate intraoperative breast
      radiation therapy.
AB  - INTRODUCTION: Intraoperative radiation therapy (IORT) is an alternative to whole
      breast radiation following breast conserving surgery. Conventional breast IORT is
      limited by lack of cross-sectional imaging. In response, our institution
      developed Precision Breast IORT (PB-IORT) which utilizes intraoperative computed
      tomography (CT) images for confirmation of brachytherapy applicator placement and
      for treatment planning. The purpose of this study was to determine the utility of
      CT imaging in PB-IORT in the first 103 patients treated in two prospective
      clinical trials. METHODS: We retrospectively reviewed the first 103 patients
      treated with PB-IORT. All patients underwent breast surgery and placement of a
      multi-lumen brachytherapy applicator. Patients had a CT scan followed by high
      dose-rate (HDR) brachytherapy. Endpoints were the number of patients having more
      than one CT during PB-IORT and the number of treatment plans having image-based
      modifications. RESULTS: After initial CT scan, 27 patients (26.2%) had findings
      prompting surgical applicator adjustment. One patient underwent an additional
      scan to localize a biopsy clip and aid in excision to negative margin. Eighty-one
      patients (78.6%) had dosimetry modifications based on CT findings with 36 plans
      (35.0%) adjusted to protect the skin or chest wall and 45 plans (43.7%) to
      protect both the skin and chest wall. CONCLUSIONS: Computed tomography findings
      prompted treatment alterations in the majority of patients treated with PB-IORT
      to enhance tissue conformity and to sculpt the radiation dose away from normal
      tissues. CT imaging is unique to PB-IORT. These findings suggest the potential
      clinical superiority of PB-IORT given its allowance for patient-specific
      alterations.

PMID- 30102021
TI  - Dental Public Health In Action: Barriers to oral healthcare provision for older
      people in residential and nursing care homes: A mixed method evaluation and
      strategy development in County Durham, North East England.
AB  - This paper presents a case study on the use of mixed methods in research into
      practice to inform policy. The study was undertaken as part of a review of oral
      healthcare for older people in residential and nursing care homes in County
      Durham, North East England. The findings highlighted challenges in the provision
      of good quality oral healthcare to older people in residential and nursing care
      homes and informed the county's oral health strategy (Durham County Council DCC,
      2016). Key recommendations include the need to develop and implement a minimum
      set of best practice oral health standards within care home contracts and train
      care home staff in oral healthcare. The paper relates to two key dental public
      health competencies: (i) designing and using mixed method studies to address gaps
      in evidence and triangulating the findings from quantitative and qualitative
      methods; (ii) the development of evidence based policies. The research is
      relevant to: care home staff; commissioners in local authority adult and social
      care; public health practitioners; oral health improvement teams; domiciliary and
      special care dentists, dental commissioners, researchers and academics.

PMID- 30102022
TI  - Scalable Synthesis of a Ruthenium-Based Electrocatalyst as a Promising
      Alternative to Pt for Hydrogen Evolution Reaction.
AB  - Designing highly active, stable, and cost-efficient electrocatalysts as
      alternatives to replace Pt is extremely desirable for hydrogen evolution reaction
      (HER). Despite much progress that has been made based on complete nonprecious
      metals (NPMs), very few NPM catalysts have shown comparable performance to Pt
      based catalysts. Herein, a cost-efficient, environmentally friendly, and scalable
      method to synthesize a novel ruthenium(Ru)-doped transition-metal carbide (Mo2C)
      hybrid catalyst was proposed. The hybrid nanoparticles were uniformly distributed
      and strongly embedded in a biomass-derived highly porous N-doped carbon
      framework. In particular, Mo2C@Ru exhibited a Pt-like remarkable electrocatalytic
      performance for HER, and it only required an extremely low overpotential of 24.6
      mV to reach the current density of 10 mA cm-2. Furthermore, our density
      functional theory calculations indicated that the nanocomposite exhibits improved
      metal-hydrogen binding and favorable hydrogen adsorption energy, which is
      comparable to that of Pt. The facile and scalable synthesis methodology, the
      relatively low cost, and the excellent electrochemical HER performance comparable
      to that of commercial Pt/C suggest that the Mo2C@Ru electrocatalyst is a
      promising alternative to Pt for large-scale hydrogen production.

PMID- 30102023
TI  - Thermogel Loaded with Low-Dose Paclitaxel as a Facile Coating to Alleviate
      Periprosthetic Fibrous Capsule Formation.
AB  - Medical-grade silicones as implants have been utilized for decades. However, the
      postoperative complications, such as capsular formation and contracture, have not
      yet been fully controlled and resolved. The aim of the present study is to
      elucidate whether the capsular formation can be alleviated by local and sustained
      delivery of low-dose paclitaxel (PTX) during the critical phase after the
      insertion of silicone implants. A biocompatible and thermogelling poly(lactic
      acid- co-glycolic acid)- b-poly(ethylene glycol)- b-poly(lactic acid- co-glycolic
      acid) triblock copolymer was synthesized by us. The micelles formed by the
      amphiphilic polymers in water could act as a reservoir for the solubilization of
      PTX, a very hydrophobic drug. The concentrated polymer aqueous solution
      containing PTX exhibited a sol-gel transition upon heating and formed a thermogel
      depot at body temperature. In vitro release tests demonstrated that the entrapped
      microgram-level PTX displayed a sustained release manner up to 57 days without a
      significant initial burst effect. Customized silicone implants coated with the
      PTX-loaded thermogels at various drug concentrations were inserted into the
      pockets of the subpanniculus carnosus plane of rats. The histological
      observations performed 1 month postoperation showed that the sustained release of
      PTX with an appropriate dose significantly reduced the peri-implant capsule
      thickness, production and deposition of collagen, and expression of contracture
      mediating factors compared with bare silicone implants. More importantly, such an
      optimum dose had an excellent repeatability for the suppression of the capsular
      formation. Therefore, this study provides a strategic foothold regarding the
      sustained release of low-dose PTX to alleviate fibrotic capsule formation after
      implantation, and the microgram-level PTX-loaded thermogel holds great potential
      as an "all-purpose antifibrosis coating" for veiling the surfaces of various
      implantable medical devices.

PMID- 30102024
TI  - The Rise of Hierarchical Nanostructured Materials from Renewable Sources:
      Learning from Nature.
AB  - Mimicking Nature implies the use of bio-inspired hierarchical designs to
      manufacture nanostructured materials. Such materials should be produced from
      sustainable sources ( e.g., biomass) and through simple processes that use mild
      conditions, enabling sustainable solutions. The combination of different types of
      nanomaterials and the implementation of different features at different length
      scales can provide synthetic hierarchical nanostructures that mimic natural
      materials, outperforming the properties of their constitutive building blocks.
      Taking recent developments in flow-assisted assembly of nanocellulose crystals as
      a starting point, we review the state of the art and provide future perspectives
      on the manufacture of hierarchical nanostructured materials from sustainable
      sources, assembly techniques, and potential applications.

PMID- 30102025
TI  - Laser-Activated Bioprobes with High Photothermal Conversion Efficiency for
      Sensitive Photoacoustic/Ultrasound Imaging and Photothermal Sensing.
AB  - Laser-activated bioprobes with high photothermal conversion efficiency (IRPDA@PFH
      NDs) based on biocompatible IR-780 doped polydopamine perfluorocarbon
      nanodroplets (NDs) were developed. When protected by gelatin microspheres, their
      near-spherical morphologies can be easily observed with transmission electron
      microscope. Doping IR-780 (3 w/w % of added dopamine hydrochloride) can
      significantly enhance near-infrared (NIR) absorption and photothermal conversion
      efficiency to 57.7%. The enhanced NIR absorption and nonradiative relaxation are
      preferred to stronger photoacoustic (PA) signals and higher PA imaging
      definition; ultrasound (US) signals also increase more than 2.5 times because of
      easier phase change of NDs. These bioprobes had sensitive PA/US imaging
      capability with highly effective substitute utilizations, in which polydopamine
      was used either as a PA contrast or a photothermal agent. Perfluorocarbon can be
      used as an US contrast agent and temperature indicator. More importantly, the
      gray value increments of US increase with temperature in a general range from 35
      to 55  degrees C. Especially, an approximate linear increasing of gray value in
      the optimized photothermal therapy (PTT) range from 35  degrees C to 50  degrees
      C could be used for the temperature monitoring and control of PTT. During PTT,
      the heated regions and the extent of photothermal heating can be visualized by US
      imaging. These findings indicate their great potential for biosensing and PTT
      monitoring.

PMID- 30102026
TI  - Stereoisomerism in Lanthanide Complexes: Enumeration, Chirality, Identification,
      Random Coordination Ratios.
AB  - The concept of random coordination ratios, RCRs, is advanced for lanthanide
      complexes. RCRs describe the relative probabilities of occurrence of subsets of
      stereoisomers of same-symmetry point groups in the limiting situation when
      energetic effects are equivalent. We then introduce a method to uniquely identify
      the stereoisomer of the coordination polyhedron of a given crystallographic
      structure and introduce a notation that fully characterizes its stereochemistry
      in an unambiguous manner, from which absolute configuration naturally follows. De
      facto, the coordination chirality in lanthanide complexes is a frequently
      overlooked property, even though these compounds often exhibit, when luminescent,
      high dissymmetry factors. With our methodology, we even managed to recognize a
      known dilanthanide complex as a meso compound, with both metal ions functioning
      as stereogenic centers. To achieve these results, we enumerate all possible
      stereoisomers of lanthanide complexes with coordination numbers from 4 to 9 for
      all combinations of monodentate, symmetric and asymmetric bidentate ligands, and
      for several shapes of coordination polyhedra. We confirmed the number of
      stereoisomers for each case by means of Polya's theorem. We further classified
      all stereoisomers according to their symmetry point groups and generated their
      Cartesian coordinates. This collection of all coordination polyhedra stereoisomer
      geometries, which is made available in the Supporting Information , can also be
      used to easily build starting-point geometries for theoretical calculations of
      metal complexes.

PMID- 30102027
TI  - Coordination-Driven Self-Assembled ZnII6-LnIII3 Metallocycles Based on a
      Salicylamide Imine Ligand: Synthesis, Structure, and Selective Luminescence
      Enhancement Induced by OAc.
AB  - Five heterometallic ZnII6-LnIII3 macrocycles based on a salicylamide imine
      multidentate unsymmetrical ligand H2L [1-(2-hydroxy-3-methoxy-benzamido)-2-(2
      hydroxy-3-methoxy-benzylideneamino)-ethane] have been prepared via a coordination
      driven self-assembly strategy. Single-crystal X-ray diffraction analysis reveals
      that the five metallocycles are isomorphic with a formula of
      [Zn6Ln3L6(OH)2(NO3)4(H2O)].3NO3. nCH3CN (ZnLn-1, where Ln = Pr, Nd, Eu, Tb, or
      Yb; for ZnPr-1, n = 4; for ZnNd-1, ZnEu-1, and ZnTb-1, n = 2; for ZnYb-1, n = 3),
      where six octadentate ligands L2- and two in situ-formed MU2-OH- ions bridged the
      alternating ZnII-LnIII-ZnII subunits into a macrocycle. Along with the structural
      novelty, ZnNd-1 shows distinctive enhanced emission in the visible and near
      infrared range upon addition of OAc-. On the basis of ultraviolet-visible
      spectroscopy, 1H nuclear magnetic resonance, single-crystal X-ray diffraction,
      and high-resolution electrospray ionization mass spectrometry, we deduced that
      this emission enhancement could be attributed to the synergistic effect of TICT
      and the absent nonradiative transition of MU2-OH- induced distinctively by OAc-
      bridging. Our results demonstrate that the NdIII-containing heterometallic
      macrocycle can act as a host for anion exchanging and provide a nice example of
      heterometallic macrocycles with interesting properties and potential
      applications.

PMID- 30102028
TI  - Three-Component Copper-Phosphonate-Auxiliary Ligand Systems: Proton Conductors
      and Efficient Catalysts in Mild Oxidative Functionalization of Cycloalkanes.
AB  - The synthesis, structural characterization, topological analysis, proton
      conductivity, and catalytic properties are reported of two Cu(II)-based
      compounds, namely a dinuclear Cu(II) complex [Cu2(MU-VPA)2(phen)2(H2O)2].8H2O (1)
      (H2VPA = vinylphosphonic acid, phen = 1,10-phenanthroline) and a 1D coordination
      polymer [Cu(MU-SO4)(phen)(H2O)2]infinity (2). Their structural features and H
      bonding interactions were investigated in detail, showing that the metal-organic
      structures of 1 and 2 are extended by multiple hydrogen bonds to more complex 2D
      or 1D H-bonded architectures with the kgd [Shubnikov plane net (3.6.3.6)/dual]
      and SP 1-periodic net (4,4)(0,2) topology, respectively. These nets are primarily
      driven by the H-bonding interactions involving water ligands and H2O molecules of
      crystallization; besides, the (H2O)4/(H2O)5 clusters were identified in 1. Both 1
      and 2 are moderate proton conductors, with proton conductivity values, sigma =
      3.65 * 10-6 and 3.94 * 10-6 S.cm-1, respectively (measured at 80  degrees C and
      95% relative humidity). Compounds 1 and 2 are also efficient homogeneous
      catalysts for the mild oxidative functionalization of C5-C8 cycloalkanes
      (cyclopentane, cyclohexane, cycloheptane, and cyclooctane), namely for the
      oxidation by H2O2 to give cyclic alcohols and ketones and the hydrocarboxylation
      by CO/H2O and S2O82- to the corresponding cycloalkanecarboxylic acids as major
      products. The catalytic reactions proceed under mild conditions (50-60  degrees
      C) in aqueous acetonitrile medium, resulting in up to 34% product yields based on
      cycloalkane substrate.

PMID- 30102029
TI  - Smart Peptide-Based Supramolecular Photodynamic Metallo-Nanodrugs Designed by
      Multicomponent Coordination Self-Assembly.
AB  - Supramolecular photosensitizer nanodrugs that combine the flexibility of
      supramolecular self-assembly and the advantage of spatiotemporal, controlled drug
      delivery are promising for dedicated, precise, noninvasive tumor therapy.
      However, integrating robust blood circulation and targeted burst release in a
      single photosensitizer nanodrug platform that can simultaneously improve the
      therapeutic performance and reduce side effects is challenging. Herein, we
      demonstrate a multicomponent coordination self-assembly strategy that is
      versatile and potent for the development of photodynamic nanodrugs. Inspired by
      the multicomponent self-organization of polypeptides, pigments, and metal ions in
      metalloproteins, smart metallo-nanodrugs are constructed based on the combination
      and cooperation of multiple coordination, hydrophobic, and electrostatic
      noncovalent interactions among short peptides, photosensitizers, and metal ions.
      The resulting metallo-nanodrugs have uniform sizes, well-defined nanosphere
      structures, and high loading capacities. Most importantly, multicomponent
      assembled nanodrugs have robust colloidal stability and ultrasensitive responses
      to pH and redox stimuli. These properties prolong blood circulation, increase
      tumor accumulation, and enhance the photodynamic tumor therapeutic efficacy. This
      study offers a new strategy to harness robust, smart metallo-nanodrugs with
      integrated flexibility and multifunction to enhance tumor-specific delivery and
      therapeutic effects, highlighting opportunities to develop next-generation, smart
      photosensitizing nanomedicines.

PMID- 30102030
TI  - Electrocatalytic Water Oxidation by an Unsymmetrical Di-Copper Complex.
AB  - An unsymmetrical di-copper complex, ([Cu2(TPMAN)(MU-OH)(H2O)]3+, was prepared and
      used for electrocatalytic water oxidation in neutral conditions. This complex is
      a stable and efficient homogeneous catalyst during the electrocatalytic oxygen
      evolution process ( kcat = 0.78 s-1) with 780 mV onset overpotential in 0.1 M
      phosphate buffer (pH 7.0). The water oxidation mechanism of the unsymmetrical
      catalyst [Cu2(TPMAN)(MU-OH)]3+ exhibits different behaviors than that of
      [Cu2(BPMAN)(MU-OH)]3+, such as two redox steps with different pH dependences, a
      significant kinetic isotope effect, and buffer concentration dependence. All
      these changes were ascribed to the open site on the Cu center that is formed by
      removal of the hemilabile pyridyl site, which acts as an intramolecular proton
      acceptor to assist the O-O bond formation step.

PMID- 30102032
TI  - Solution-State Anion Recognition, and Structural Studies, of a Series of Electron
      Rich meta-Phenylene Bis(phenylurea) Receptors and Their Self-Assembled
      Structures.
AB  - meta-Phenylene bis(phenylurea) receptors 1-4 were designed and synthesized to
      investigate the association between receptor shape, anion-selective binding and
      anion-directed self-assembly processes. Solution studies, performed through 1H
      NMR titrations with a variety of tetra- N-butylammonium salts, demonstrated
      strong binding of 2 equiv of H2PO4-, AcO-, BzO- anions and comparatively weak
      binding of Cl-, HSO4-, and SO42- anions. Binding modes and stability constants
      (log beta) were determined by regression analysis of the obtained 1H NMR
      titration data in DMSO- d6, and the cooperativities of the binding interactions
      were probed. Host-guest complexes of receptors 1 and 2 were studied in the
      crystalline phase to further probe the anion-binding behavior of this motif. This
      included a triple-stranded helicate consisting of three strands of receptor 2
      arranged around a mixed-phosphate anionic core, which was characterized by using
      X-ray crystallography.

PMID- 30102033
TI  - RNA as a Complex Polymer with Coupled Dynamics of Ions and Water in the Outer
      Solvation Sphere.
AB  - We unravel the internal and collective modes of a widely studied 58-nucleotide
      rRNA fragment in solvent using atomically detailed molecular dynamics
      simulations. The variation of lifetimes for water hydrogen bonds with nucleotide
      groups indicates heterogeneity of water dynamics on the RNA surface. The time
      scales of interactions of the discrete water molecules with RNA nucleotides
      extend from several hundred picoseconds to a few nanoseconds. We determine all of
      the association sites and the spatial distribution of residence times for Mg2+,
      K+, and water molecules in those sites. We provide insights into the population
      of Mg2+ and K+ ions and water molecules in the outer sphere and how their
      fluctuations are intricately linked with the kinetics of the 58-mer. We find that
      many of the long-lived Mg2+ sites identified from the simulations agree with the
      locations of ions in the X-ray structure. We determine the excess ion atmosphere
      around the rRNA and compare it with experimental data. We investigate the
      collective behavior of RNA, ions, and water, by performing a joint principle
      component analysis for the Cartesian coordinates of the RNA phosphorus atoms and
      for the occupation counts of the association sites. Our results indicate that the
      58-mer system is a complex polymer, composed of RNA that is encased by a
      fluctuating network of associated counterions, co-ions, and water.

PMID- 30102034
TI  - Solvent and Temperature Effects on Dynamics and Chiroptical Properties of
      Propeller Chirality and Toroidal Interaction of Hexaarylbenzenes.
AB  - Because of the unique interaction of radial aromatic blades, propeller-shaped
      hexaarylbenzenes (HABs) attract much research interest and find various practical
      applications. By introducing a small point-chiral group at the tip of aromatic
      blade(s), HAB becomes propeller-chiral to exhibit strong Cotton effects. Because
      of the dynamic nature of propeller chirality, the chiroptical properties of HAB
      critically responded to minute changes in the environment. Using a series of
      chiral HABs with one to six ( R)-1-methylpropyloxy substituent(s) introduced at
      the blade tip, we elucidated how the smallest chiral auxiliary at the HAB
      periphery progressively and cooperatively boosts the overall chiroptical
      properties and also how subtle changes in temperature and solvent structure
      affect the propeller dynamics and thus the chiroptical responses. The unique
      features of propeller-chiral HABs further enabled us to switch on/off their
      circularly polarized luminescence.

PMID- 30102036
TI  - Syntheses of Diverse Donor-Substituted Bisbenzofuro[2,3- b:3',2'- e]pyridines
      (BBZFPys) via Pd Catalysis, and Their Photophysical Properties.
AB  - A series of bisbenzofuro[2,3- b:3',2'- e]pyridines (BBZFPys) bearing a chlorine
      functionality have been efficiently synthesized through a Pd-catalyzed double
      oxidative intramolecular C-H/C-H coupling of monochlorinated 2,6
      diaryloxypyridines. The subsequent Buchwald-Hartwig amination of the chlorinated
      BBZFPys allowed for the access to a new class of donor-acceptor (D-A) pi
      conjugated compounds that comprise BBZFPy as an electron acceptor (A) and
      diarylamines as a donor (D) unit. The investigation of the steady-state
      photophysical properties of the prepared D-A compounds revealed that they are
      emissive in both solution and solid states in the blue-to-green color region. The
      singlet-triplet energy splitting (Delta EST) was found to be much smaller than
      that of substituent-free BBZFPy (0.70 eV), ranging from 0.01 to 0.56 eV. The time
      resolved spectroscopy revealed that the D-A compounds, comprising a bis( tert
      butyl)carbazole as the D and CF3-attached BBZFPy as the A, showed delayed
      fluorescence (DF) in nonpolar matrix host material (Zeonex), while in a polar
      matrix (DPEPO), room-temperature phosphorescence (RTP) was faintly observed.
      Furthermore, organic light-emitting diodes (OLEDs) fabricated with the D-A
      compounds as a blue emitter showed a moderate external quantum efficiencies
      (EQEs) up to 1.5%.

PMID- 30102035
TI  - Enantioselective Synthesis of a gamma-Secretase Modulator via Vinylogous Dynamic
      Kinetic Resolution.
AB  - Two efficient asymmetric routes to gamma-secretase modulator BMS-932481, under
      investigation for Alzheimer's disease, have been developed. The key step for the
      first route involves a challenging enantioselective hydrogenation of an
      unfunctionalized trisubstituted alkene to establish the benzylic stereocenter,
      representing a very rare case of achieving high selectivity on a complex
      substrate. The second route demonstrates the first example of a vinylogous
      dynamic kinetic resolution (VDKR) ketone reduction, where the carbonyl and the
      racemizable stereocenter are not contiguous, but are conjugated through a
      pyrimidine ring. Not only did this transformation require both catalyst and
      substrate control to correctly establish the two stereocenters, but it also
      necessitated that the nonadjacent benzylic center of the ketone substrate be more
      acidic than that of the alcohol product to make the process dynamic. DFT
      computations aided the design of this novel VDKR pathway by reliably predicting
      the relative acidities of the intermediates involved.

PMID- 30102037
TI  - Total Syntheses of 3- epi-Litsenolide D2 and Lincomolide A.
AB  - The first total syntheses of 3- epi-litsenolide D2 and its enantiomer lincomolide
      A were achieved. The synthetic highlights of our approach include olefin cross
      metathesis and bromine addition to the generated double bond, followed by the
      regioselective HBr-elimination and intramolecular carbonylation using
      bis(triphenylphosphine)dicarbonylnickel. This investigation also revealed that
      the previously reported specific optical rotation of 3- epi-litsenolide D2 should
      be revised.

PMID- 30102038
TI  - Ligand-Binding Ability of a Porphyrin Core in a Dendrimer with Rigid Branched
      Terminal Components.
AB  - A dendrimer with rigid branched terminal components was prepared by a copper
      catalyzed Huisgen 1,3-dipolar cycloaddition reaction. A zinc 5,15-diethynyl-10,20
      bis(3,5-di- tert-butylphenyl)porphyrin unit was incorporated at the core of the
      dendrimer as a receptor site for an added pyridyl ligand. The appearance of an
      absorption band characteristic of the planar conformer of conjugated chains in
      the terminal components suggested that the dendrimer adopts a folded higher order
      structure in dichloromethane at 25  degrees C. The binding constant between the
      zinc porphyrin core and a pyridyl ligand was evaluated by means of UV-vis
      absorption titration and compared with that of a suitable reference compound. The
      incorporation of the zinc porphyrin core into the folded dendrimer led to
      considerable suppression of its ligand-binding ability.

PMID- 30102039
TI  - Effect of Memory and Active Forces on Transition Path Time Distributions.
AB  - An analytical expression is derived for the transition path time distribution for
      a one-dimensional particle crossing of a parabolic barrier. Two cases are
      analyzed: (i) a non-Markovian process described by a generalized Langevin
      equation with a power-law memory kernel and (ii) a Markovian process with a noise
      violating the fluctuation-dissipation theorem, modeling the stochastic dynamics
      generated by active forces. In case i, we show that the anomalous dynamics
      strongly affect the short time behavior of the distributions, but this happens
      only for very rare events not influencing the overall statistics. At long times
      the decay is always exponential, in disagreement with a recent study suggesting a
      stretched exponential decay. In case ii, the active forces do not substantially
      modify the short time behavior of the distribution but do lead to an overall
      decrease of the average transition path time. These findings offer some novel
      insights, useful for the analysis of experiments of transition path times in
      (bio)molecular systems.

PMID- 30102040
TI  - Cyano-Sacrificial (Arylthio)arylamination of Quinoline and Isoquinoline N-Oxides
      Using N-(2-(Arylthio)aryl)cyanamides.
AB  - A copper(I)-catalyzed regioselective arylthio-arylamination of quinoline and
      isoquinoline N-oxides has been achieved at the expense of a cyano (CN) group from
      N-(2-(arylthio)aryl)cyanamides. This reductive amination proceeds in one pot at
      80  degrees C in the absence of any additives. This is a unique demonstration of
      aryl cyanamides serving as arylaminating agents on quinoline/isoquinoline N
      oxides with concurrent autoreduction of N-oxide.

PMID- 30102042
TI  - Interface Residues That Drive Allosteric Transitions Also Control the Assembly of
      l-Lactate Dehydrogenase.
AB  - The allosteric enzyme, l-lactate dehydrogenase (LDH), is activated by fructose
      1,6-metaphosphate (FBP) to reduce pyruvate to lactate. The molecular details of
      the FBP-driven transition from the low affinity T state to the high affinity R
      state in LDH, a tetramer composed of identical subunits, are not known. The
      dynamics of the T -> R allosteric transition, investigated using Brownian
      dynamics (BD) simulations of the self-organized polymer (SOP) model, revealed
      that coordinated rotations of the subunits drive the T -> R transition. We used
      the structural perturbation method (SPM), which requires only the static
      structure, to identify the allostery wiring diagram (AWD), a network of residues
      that transmits signals across the tetramer, as LDH undergoes the T -> R
      transition. Interestingly, the residues that play a major role in the dynamics,
      which are predominantly localized at the interfaces, coincide with the AWD
      identified using the SPM. Although the allosteric pathways are highly
      heterogeneous, on the basis of our simulations, we surmise that predominantly the
      conformational changes in the T -> R transition start from the region near the
      active site, comprised of helix alphaC, helix alpha1/2G, helix alpha3G, and helix
      alpha2F, and proceed to other structural units, thus completing the global
      motion. Brownian dynamics simulations of the tetramer assembly, triggered by a
      temperature quench from the fully disrupted conformations, show that the
      bottleneck for assembly is the formation of the correct orientational registry
      between the subunits, requiring contacts between the interface residues.
      Surprisingly, these residues are part of the AWD, which was identified using the
      SPM. Taken together, our results show that LDH, and perhaps other multidomain
      proteins, may have evolved to stabilize distinct states of allosteric enzymes
      using precisely the same AWD that also controls the functionally relevant
      allosteric transitions.

PMID- 30102041
TI  - Lentil ( Lens culinaris Medikus) Diet Affects the Gut Microbiome and Obesity
      Markers in Rat.
AB  - Lentil, a moderate-energy high-protein pulse crop, provides significant amounts
      of essential nutrients for healthy living. The objective of this study was to
      determine if a lentil-based diet affects food and energy intake, body weight,
      percent body fat, liver weight, and body plasma triacylglycerols (TGs) as well as
      the composition of fecal microbiota in rats. A total of 36 Sprague-Dawley rats
      were treated with either a standard diet, a 3.5% high amylose corn starch diet,
      or a 70.8% red lentil diet for 6 weeks. By week 6, rats fed the lentil diet had
      significantly lower mean body weight (443 +/- 47 g/rat) than those fed the
      control (511 +/- 51 g/rat) or corn (502 +/- 38 g/rat) diets. Further, mean
      percent body fat and TG concentration were lower, and lean body mass was higher
      in rats fed the lentil diet than those fed the corn diet. Fecal abundance of
      Actinobacteria and Bacteriodetes were greater in rats fed the lentil or corn
      starch diets than those fed the control diet. Fecal abundance of Firmicutes, a
      bacterial phylum comprising multiple pathogenic species, decreased in rats fed
      the lentil and high-amylose corn starch diets vs the control diet. The lentil
      based diet decreased body weight, percent body fat, and plasma triacylglycerols
      in rats and suppressed intestinal colonization by pathogens.

PMID- 30102043
TI  - Molecular-Level Structure and Packing in Phase-Separated Arachidic Acid
      Perfluorotetradecanoic Acid Monolayer Films.
AB  - Synchrotron-based X-ray scattering measurements of phase-separated surfactant
      monolayers at the air-water interface provide molecular-level structural
      information about the packing and ordering of film components. In this work,
      grazing incidence X-ray diffraction (GIXD) and X-ray reflectivity (XR)
      measurements were used to collect crystallographic structural information for
      binary mixed monolayers of arachidic acid (AA, C19H39COOH) with
      perfluorotetradecanoic acid (PA, C13F27COOH), a system that has previously been
      investigated using a variety of thermodynamic and micron-scale structural
      characterization methods. GIXD measurements at surface pressures of pi = 5, 15,
      and 30 mN/m indicated that AA in pure and mixed films forms a rectangular lattice
      at pi = 5 and 15 mN/m but a hexagonal lattice at pi = 30 mN/m. PA formed
      hexagonal lattices under all conditions, with films being highly ordered and
      crystalline (as determined by Bragg peak width) at even the lowest surface
      pressures investigated. Phase separation occurred for all mixed monolayer film
      compositions and surface pressures, manifesting as diffraction peaks
      characteristic of the individual components appearing at different in-plane
      scattering vector qxy. For both pure and mixed films, the molecular tilt angle of
      the AA hydrocarbon chain toward the nearest-neighbor was substantial at low
      pressures but decreased with increasing pressure. The PA fluorocarbon chain
      showed negligible molecular tilt under all conditions, and was oriented normal to
      the subphase surface regardless of surface pressure or the presence of AA in the
      films. In all cases, the two components in the mixed film behaved entirely
      independently of film composition, which is exactly the expected result for a
      fully phase-separated, immiscible system. XR measurements of film thickness at
      the air-water interface supported these results; overall film thickness
      approached the calculated ideal surfactant tail lengths with increasing surface
      pressure, indicating nearly normal oriented surfactants. The overall surfactant
      packing and crystallographic features of the mixed monolayers are discussed in
      terms of the lipophobic nature of the perfluorinated surfactant as well as in
      context of thermodynamic miscibility and domain structure formation reported
      elsewhere in the literature for these mixed monolayer systems.

PMID- 30102044
TI  - Mechanism of SmI2 Reduction of 5-Bromo-6-oxo-6-phenylhexyl Methanesulfonate
      Studied by Spin Trapping with 2-Methyl-2-nitrosopropane.
AB  - The radical formed by reduction of 5-bromo-6-oxo-6-phenylhexyl methanesulfonate,
      an alpha-bromoketone, with SmI2 was spin trapped with 2-methyl-2-nitrosopropane.
      Electron paramagnetic resonance spectra of the spin adduct and the adduct formed
      in the analogous reaction with selectively deuterated substrate identify the
      radical intermediate in this SmI2 reduction as a carbon-centered radical. This
      result supports the proposal that the formation of reactive Sm-enolates arises
      from reduction of the carbon-bromine bond rather than a ketyl radical anion.

PMID- 30102045
TI  - Visible-Light-Induced C(sp2)-P Bond Formation by Denitrogenative Coupling of
      Benzotriazoles with Phosphites.
AB  - A visible-light-induced denitrogenative phosphorylation of benzotriazoles is
      presented, in which diverse substituted aryl phosphonates could be obtained in
      good to excellent yields. This efficient protocol exhibits good tolerance with
      various functional groups. Furthermore, the utility of this photochemical
      protocol is demonstrated by a gram-scale reaction, and a reasonable mechanism is
      proposed.

PMID- 30102046
TI  - Rhodium-Catalyzed Formylation of Aryl Halides with CO2 and H2.
AB  - The reductive formylation of aryl iodides/bromides to aryl aldehydes using CO2/H2
      is presented for the first time. It was realized over a catalytic system composed
      of RhI3 or RhI3/Pd(dppp)Cl2 (dppp = 1,3-bis(diphenyphosphino)propane) and PPh3 in
      the presence of Ac2O/Et3N at 100  degrees C, affording aromatic aldehydes in good
      to excellent yields, together with good functional-group tolerance and broad
      substrate scope. The reaction proceeds through three cascade steps, involving
      HCOOH formation, CO release, and formylation of aryl halides.

PMID- 30102047
TI  - Accessible Bifunctional Oxy-Tethered Ruthenium(II) Catalysts for Asymmetric
      Transfer Hydrogenation.
AB  - A concise synthesis of new oxy-tethered ruthenium complexes effective for the
      asymmetric transfer hydrogenation of aromatic ketones is described. The oxy
      tether was constructed via a defluorinative etherification arising from an
      intramolecular nucleophilic substitution of a perfluorinated phenylsulfonyl
      substituent. The obtained tethered complexes exhibited desirable catalytic
      activity and selectivity, especially in the asymmetric transfer hydrogenation of
      functionalized aromatic ketones. The robustness and rigidity of the tether
      contribute to their superior catalytic performance relative to the nontethered
      prototype complex.

PMID- 30102048
TI  - Gold-Catalyzed Oxidative Cyclizations of { o-(Alkynyl)phenyl propargyl} Silyl
      Ether Derivatives Involving 1,2-Enynyl Migration: Synthesis of Functionalized 1 H
      Isochromenes and 2 H-Pyrans.
AB  - A new and convenient strategy for the synthesis of functionalized 1 H-isochromene
      and 2 H-pyran derivatives based on gold-catalyzed oxidative cyclizations of o
      (alkynyl)phenyl propargyl ether derivatives has been developed. The reaction
      proceeds via gold-catalyzed highly regioselective oxidation, followed by 1,2
      migration of an enynyl group and nucleophlic addition. Isocoumarins were also
      constructed through oxidative cleavage of the exocyclic double bond of the
      obtained 1 H-isochromenes.

PMID- 30102049
TI  - Vertically Aligned Porous Organic Semiconductor Nanorod Array Photoanodes for
      Efficient Charge Utilization.
AB  - Because of inefficient charge utilization caused by localized pi-electron
      conjugation and large exciton binding energy, the photoelectrochemical water
      splitting efficiency of organic polymers is seriously limited. Taking the
      graphitic carbon nitride (g-CN) polymer as an example, we report a novel
      photoanode based on a vertically aligned g-CN porous nanorod (PNR) array prepared
      in situ, using a thermal polycondensation approach, with anodic aluminum oxide as
      the template. The g-CN PNR array exhibits an excellent photocurrent density of
      120.5 MUA cm-2 at 1.23 VRHE under one sun illumination, the highest reported
      incident photon-to-current efficiency of ~15% at 360 nm, and an outstanding
      oxygen evolution reaction stability in 0.1 M Na2SO4 aqueous solution, which
      constitutes a benchmark performance among the reported g-CN-based polymer
      photoanodes without any sacrificial reagents. When compared with its planar
      counterpart, the enhanced performance of the PNR array results principally from
      its unique structure that enables a high degree of aromatic ring pi-electron
      conjugation for higher mobility of charge carriers, provides a direct pathway for
      the electron transport to the substrate, produces a large portion of hole
      accepting defect sites and space charge region to promote exciton dissociation,
      and also withstands more strain at the interface to ensure intimate contact with
      the substrate. This work opens a new avenue to develop nanostructured organic
      semiconductors for large-scale application of solar energy conversion devices.

PMID- 30102050
TI  - Collaborative decision skills training: Feasibility and preliminary outcomes of a
      novel intervention.
AB  - Increasing consumer empowerment and agency in treatment decision-making is a
      priority for improving recovery among people with serious mental illness (SMI),
      as it is associated with a number of positive outcomes, including improved
      treatment engagement and satisfaction. Although there are many tools to promote
      initiation of shared decision-making by providers, there are few tools empowering
      consumers to independently initiate collaborative decision-making (CDM).
      Therefore, this study tests the feasibility of a novel skills training
      intervention for outpatients with SMI, collaborative decision skills training
      (CDST). Twenty-one consumers with SMI currently receiving community-based day
      services participated in CDST. Four areas of feasibility were assessed
      acceptability, demand, practicality, and preliminary evidence of efficacy.
      Feasibility results were favorable, including high acceptability and
      practicality. Demand results were mixed: rates of attendance were high and
      attrition was low, but participants did not complete homework as often as
      expected. Finally, there was evidence CDST has a positive impact on targeted
      outcomes; participants reported an increased sense of personal recovery, and
      displayed improvements in both knowledge and skills targeted by CDST. CDST is
      feasible to implement with fidelity and is received well by participants. Next
      steps include larger controlled trials of CDST, which will better inform efficacy
      and implementation related questions. (PsycINFO Database Record

PMID- 30102051
TI  - Improving parental emotion socialization in military families: Results of a
      randomized controlled trial.
AB  - Prior research indicates that children of deployed parents are at risk for
      emotional problems, suggesting the utility of preventive efforts for military
      families. Effective parental socialization of children's emotions is protective
      for children's development, and parental experiential avoidance may impede
      parental emotion socialization, yet intervention studies in this area are
      lacking. This study examined the impact of a parenting program, After Deployment
      Adaptive Parenting Tools (ADAPT), on parental emotion socialization
      postintervention (6 months postbaseline) and whether intervention effects were
      moderated by parental experiential avoidance. The sample included 336 families
      (294 fathers and 313 mothers) with at least 1 deployed parent and a focal child
      aged 4-12. Families were randomized into either ADAPT (a 14-week group-based
      intervention) or control group. Self-reported data on parental emotion
      socialization and experiential avoidance were analyzed using structural equation
      modeling. Results showed that mothers who were assigned to the intervention had
      significant improved supportive emotion socialization and reduced nonsupportive
      emotion socialization at postintervention compared with controls. Mothers with
      higher levels of experiential avoidance assigned to the intervention group had
      higher levels of supportive emotion socialization at postintervention. No
      significant intervention effects were found in fathers. This study provides
      support for the effects of the ADAPT program on maternal emotion socialization at
      6-month postbaseline, and the role of experiential avoidance as a moderator. We
      discuss findings in relation to the different parental roles that mothers and
      fathers play in postdeployed families, as well as implications for personalized
      intervention programming. (PsycINFO Database Record

PMID- 30102052
TI  - Difficulties with being socially accepted: An experimental study in borderline
      personality disorder.
AB  - Anxious preoccupation with real or imagined abandonment is a key feature of
      borderline personality disorder (BPD). Recent experimental research suggests that
      patients with BPD do not simply show emotional overreactivity to rejection.
      Instead, they experience reduced connectedness with others in situations of
      social inclusion. Resulting consequences of these features on social behavior are
      not investigated yet. The aim of the present study was to investigate the
      differential impact of social acceptance and rejection on social expectations and
      subsequent social behavior in BPD. To this end, we developed the Mannheim Virtual
      Group Interaction Paradigm in which participants interacted with a group of
      computer-controlled avatars. They were led to believe that these represented real
      human coplayers. During these interactions, participants introduced themselves,
      evaluated their coplayers, assessed their social expectations and received
      feedback signaling either acceptance or rejection by the alleged other
      participants. Subsequently, participants played a modified trust game, which
      measured cooperative and aggressive behavior. Fifty-six nonmedicated BPD patients
      and 56 healthy control participants were randomly and double-blindly assigned to
      either the group-acceptance or group-rejection condition. BPD patients showed
      lower initial expectations of being socially accepted than healthy controls.
      After repeated presentation of social feedback, they adjusted their expectations
      in response to negative, but not to positive feedback. After the experience of
      social acceptance, BPD patients behaved less cooperatively. These experimental
      findings point to a clinically relevant issue in BPD: Altered cognitive and
      behavioral responses to social acceptance may hamper the forming of stable
      cooperative relationships and negatively affect future interpersonal
      relationships. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30102053
TI  - Timing of adolescent emotional disclosures: The role of maternal emotions and
      adolescent age.
AB  - Adolescent disclosure is a positive feature of parent-adolescent relationships,
      though disclosure to parents typically declines across adolescence. However,
      little is known about parental emotions that facilitate or inhibit real-time
      adolescent disclosures about their emotions and how parents respond to such
      disclosures during parent-adolescent interactions. The present study tested (1)
      whether maternal emotions were associated with the time to adolescents'
      spontaneous emotional disclosures and (2) whether these associations varied as a
      function of adolescent age. Adolescents (N = 49, Mage = 14.84 years) and their
      mothers participated in a 10-min conflict discussion. Adolescent emotional
      disclosures and maternal emotions were coded moment-to-moment. Results from
      survival analysis demonstrated that older adolescents whose mothers expressed
      high levels of negative affect or high levels of validation were more likely to
      make emotional disclosures earlier in the discussion than were older adolescents
      whose mothers expressed low negative affect or low validation. There were no
      differences in associations between maternal emotions and the timing of emotional
      disclosures for younger adolescents. Findings suggest that a range of maternal
      emotions (validation and negative affect) might be features of high-quality
      mother-adolescent relationships in older adolescence, when parent-adolescent
      relationships are more egalitarian and negative emotions may be more readily
      expressed. Implications for applying observational methodologies and dynamic
      statistical techniques to the adolescent disclosure literature are discussed.
      (PsycINFO Database Record

PMID- 30102054
TI  - Alternating optimization for G * E modelling with weighted genetic and
      environmental scores: Examples from the MAVAN study.
AB  - Motivated by the goal of expanding currently existing Genotype * Environment
      interaction (G * E) models to simultaneously include multiple genetic variants
      and environmental exposures in a parsimonious way, we developed a novel method to
      estimate the parameters in a G * E model, where G is a weighted sum of genetic
      variants (genetic score) and E is a weighted sum of environments (environmental
      score). The approach uses alternating optimization, an iterative process where
      the genetic score weights, the environmental score weights, and the main model
      parameters are estimated in turn, assuming the other parameters are constant.
      This technique can be used to construct relatively complex interaction models
      that are constrained to a particular structure, and hence contain fewer
      parameters. We present the model as a 2-way interaction longitudinal mixed model,
      for which ordinary linear regression is a special case, but it can easily be
      extended to be compatible with k-way interaction models and generalized linear
      mixed models. The model is implemented in R (LEGIT package) and using SAS macros
      (LEGIT_SAS). Through simulations, we demonstrate the power and validity of this
      approach even with small sample sizes. Furthermore, we present examples from the
      Maternal Adversity, Vulnerability, and Neurodevelopment (MAVAN) study where we
      improve significantly upon already existing models using alternating
      optimization. (PsycINFO Database Record

PMID- 30102055
TI  - Employers' implicit attitudes about the competence of people who are blind.
AB  - OBJECTIVE: The purpose of this study was to develop and validate an implicit
      measure of attitudes about the competence of people who are blind, to be used
      with employers, and to report on these implicit attitudes with a national sample
      of employers. METHOD: A sample of 343 employers (i.e., business professionals
      responsible for making hiring decisions) participated in an online survey that
      involved answering questions and completing formal instruments, including
      explicit and implicit attitude measures about blind employees and a knowledge
      measure about how blind people can perform typical work tasks. The implicit
      measure was an Implicit Association Test-Blind/Visually Impaired (the IAT-BVI)
      that was developed for this study. RESULTS: Employers have strong negative
      implicit attitudes about the competence of people who are blind, with results
      indicating a very large IAT effect. These implicit attitudes were not associated
      with personal characteristics, exposure to people who are blind, or explicit
      attitudes. Implicit attitudes were significantly associated with knowledge about
      how blind people perform work tasks and, for employers who had hired a blind
      person, performance ratings of those employees. CONCLUSIONS: Employers' implicit
      attitudes about the competence of blind people were mostly unrelated to other
      measures, as expected, with the exception of knowledge and performance ratings of
      blind employees. These findings provide support for the validity of the IAT-BVI,
      and indicate the importance of rehabilitation professionals working with
      employers to provide education about how blind people perform work tasks as a
      potential avenue to improve employment opportunities for people who are blind.
      (PsycINFO Database Record (c) 2018 APA, all rights reserved).

PMID- 30102056
TI  - Predicting reading comprehension in young children with autism spectrum disorder.
AB  - Relationships between early literacy measures (i.e., curriculum-based
      measurement) and advanced literacy measures (i.e., reading comprehension) were
      examined in young children with autism spectrum disorders (ASDs). Participants in
      this study were 167 children between the ages of 4 and 7 years (M = 5 years 8
      months), who were assessed at 2 time points during 1 school year. Results
      indicated that, compared to other measures of early literacy skills, curriculum
      based measurements (CBMs) accurately assessed skills in students with ASD.
      Furthermore, early literacy skills predicted reading comprehension approximately
      six months later in this sample. The reading development of children with ASD
      compared to typically developing children appears to be similar in the predictive
      capacity of decoding skills on later reading skills and dissimilar in the
      variability and range of skills. CBM tools can provide educators with information
      about the early reading skills of children with ASD to help address reading and
      language difficulties seen in this population. (PsycINFO Database Record

PMID- 30102057
TI  - Examining false-positive rates of Wechsler Adult Intelligence Scale (WAIS-IV)
      processing speed-based embedded validity indicators among individuals with
      schizophrenia spectrum disorders.
AB  - Recent research (Erdodi et al., 2017) indicated that certain Wechsler Adult
      Intelligence Scale (WAIS-IV) Processing Speed Index (PSI)-based indices may have
      some utility as embedded validity indicators (EVIs) among a diagnostically
      diverse sample of neuropsychology referrals. Individuals with schizophrenia
      spectrum disorders (SSD) are often evaluated in forensic contexts in which there
      is incentive to exaggerate deficits. Because individuals with SSD often have
      limitations in processing speed associated with their disorders, the current
      study sought to evaluate the false-positive (FP) rates of cutoffs identified by
      Erdodi et al. on WAIS-IV PSI-based EVIs among forensically committed psychiatric
      inpatients with SSD who had no known incentive to feign because of the nature of
      their legal commitments. In the current sample, the previously suggested cutoff
      scores on PSI-based EVIs resulted in FP rates ranging from 2% to 57% among
      schizophrenia spectrum patients, with unacceptable FP rates for most indices. In
      the current sample of SSD patients, WAIS-IV PSI-based EVIs that are calculated
      based on the relative performance between PSI subtests (as opposed to absolute
      performance on individual indices) demonstrated acceptable FP rates. (PsycINFO
      Database Record

PMID- 30102059
TI  - Homeless people in Leon (Nicaragua): Conceptualizing and measuring homelessness
      in a developing country.
AB  - Homelessness is a global phenomenon that affects groups in situations of poverty
      and social exclusion, in both developed and developing nations. However, the
      scientific literature on homeless people in developing countries is scant. This
      work shows the difficulties defining homelessness and examines the necessary
      criteria for who will be deemed a homeless person in a developing country.
      Furthermore, the results of the Point-In-Time (PIT) count of homeless people-a
      measure of the number of homeless people on a specific day-done in the city of
      Leon, Nicaragua (population: 185,000). Throughout the PIT count, 82 unduplicated
      people living in homelessness were tallied (76% male, 23% female), of which 47
      answered a questionnaire. Most of the homeless people in Leon are male, mestizo,
      of Nicaraguan nationality, with a primary level education or less, and in a
      situation of chronic homelessness. Results showed a mean age of 47 years for
      these individuals. Most of the homeless people showed a bad physical appearance,
      had poor personal hygiene, and wore dirty clothing. Around half of the homeless
      observed seemed to have problems related to mental health, alcohol, and/or drugs.
      (PsycINFO Database Record

PMID- 30102060
TI  - Longitudinal actor, partner, and similarity effects of personality on well-being.
AB  - The current study aimed to conceptually replicate previous studies on the effects
      of actor personality, partner personality, and personality similarity on general
      and relational well-being by using response surface analyses and a longitudinal
      sample of 4,464 romantic couples. Similar to previous studies using difference
      scores and profile correlations, results from response surface analyses indicated
      that personality similarity explained a small amount of variance in well-being as
      compared with the amount of variance explained by linear actor and partner
      effects. However, response surface analyses also revealed that second-order terms
      (i.e., the interaction term and quadratic terms of actor and partner personality)
      were systematically linked to couples' well-being for all traits except
      neuroticism. In particular, most response surfaces showed a complex pattern in
      which the effect of similarity and dissimilarity on well-being depended on the
      level and combination of actor and partner personality. In addition, one small
      but robust similarity effect was found, indicating that similarity in
      agreeableness was related to women's experience of support across the eight years
      of the study. The discussion focuses on the implications of these findings for
      theory and research on personality similarity in romantic relationships.
      (PsycINFO Database Record

PMID- 30102058
TI  - Binocular summation revisited: Beyond ?2.
AB  - Our ability to detect faint images is better with two eyes than with one, but how
      great is this improvement? A meta-analysis of 65 studies published across more
      than 5 decades shows definitively that psychophysical binocular summation (the
      ratio of binocular to monocular contrast sensitivity) is significantly greater
      than the canonical value of ?2. Several methodological factors were also found to
      affect summation estimates. Binocular summation was significantly affected by
      both the spatial and temporal frequency of the stimulus, and stimulus speed (the
      ratio of temporal to spatial frequency) systematically predicts summation levels,
      with slow speeds (high spatial and low temporal frequencies) producing the
      strongest summation. We furthermore show that empirical summation estimates are
      affected by the ratio of monocular sensitivities, which varies across
      individuals, and is abnormal in visual disorders such as amblyopia. A simple
      modeling framework is presented to interpret the results of summation
      experiments. In combination with the empirical results, this model suggests that
      there is no single value for binocular summation, but instead that summation
      ratios depend on methodological factors that influence the strength of a
      nonlinearity occurring early in the visual pathway, before binocular combination
      of signals. Best practice methodological guidelines are proposed for obtaining
      accurate estimates of neural summation in future studies, including those
      involving patient groups with impaired binocular vision. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30102061
TI  - How to give away your cake and eat it too: Relinquishing control prompts
      reciprocal generosity.
AB  - Many resource allocations confer two rewards, but these rewards typically work in
      opposition to one another: Reputational rewards come to those who give and
      material rewards to those who receive. Eight studies reveal that abdicating a
      resource allocation decision-that is, giving away one's right to choose to
      someone else-may allow these two rewards to work in tandem. We found that people
      frequently abdicated to others, and abdication often prompted others to
      reciprocate by giving away the better of two items. This occurred in part because
      people perceived abdication to be generous; in fact, individuals who abdicated
      seemed nearly as generous as individuals who gave away the better item to begin
      with. Paradoxically, abdicating confers both the reputational benefits of giving
      and (often) the material benefits of getting. This finding has implications for
      everyday resource sharing behavior and as well as for theories of fairness and
      reciprocity. (PsycINFO Database Record

PMID- 30102063
TI  - Rapid nicotine tolerance and cross-tolerance to varenicline in rhesus monkeys:
      Drug discrimination.
AB  - Acute tolerance to effects of nicotine plays an important role in nicotine
      dependence, but the mechanism underlying these effects is unclear. Drug
      discrimination was used in the current study to examine the impact of nicotine
      pretreatment on sensitivity to the discriminative stimulus effects of nicotine
      and the FDA-approved smoking cessation pharmacotherapy varenicline. Rhesus
      monkeys (n = 4) discriminated 0.032 mg/kg nicotine base iv from saline under an
      FR5 schedule of stimulus-shock termination. Both nicotine and varenicline
      increased drug-appropriate responding; ED50 values (95% confidence limits) were
      0.0087 [0.0025, 0.030] and 0.028 [0.0096, 0.082] mg/kg, respectively. Additional
      pretreatment injections of the training dose of nicotine (0.032 mg/kg, iv)
      produced tolerance to its discriminative stimulus effects and the magnitude of
      this effect was related to the number of pretreatment injections administered.
      Two pretreatment injections of the training dose of nicotine (0.032 mg/kg, iv)
      produced a 5.4-fold rightward shift in the nicotine dose-response function and a
      sevenfold rightward shift in the varenicline dose-response function. The duration
      of tolerance under these conditions was less than 60 min. These results
      demonstrate that tolerance to the discriminative stimulus effects of nicotine can
      be produced by acute nicotine exposure. Acute cross-tolerance from nicotine to
      varenicline is consistent with similar actions at nAChRs, and suggests that
      conditions resulting in acute nicotine tolerance could impact sensitivity to
      other nAChR agonists. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30102062
TI  - Differences in puff topography, toxicant exposure, and subjective response
      between waterpipe tobacco smoking men and women.
AB  - Waterpipe tobacco smoking (WTS) exposes users to toxicants in much greater
      amounts than a cigarette. Little is known about how gender affects WTS toxicant
      exposure and subjective response. Data from three WTS clinical laboratory studies
      were combined for analysis. Participants (N = 99; 38 women) completed a 45-min
      WTS session where they smoked a waterpipe ad libitum. Puff topography was
      measured throughout, and plasma nicotine concentration, expired air carbon
      monoxide (CO), and subjective responses were measured pre- and post-WTS. There
      was a gender effect for total puff volume with men inhaling a greater smoke
      volume, on average (M = 59.9 L, SD = 40.7), compared with women (M = 38.8 L, SD =
      27.8; p < .01). Men had greater post-WTS mean plasma nicotine concentrations (M =
      10.0 ng/ml, SD = 7.1) compared with women (M = 6.9 ng/ml, SD = 5.2; p < .05).
      Post-WTS expired air CO was not associated with gender (men M = 27.6 ppm, SD =
      18.9; women M = 22.7 ppm, SD = 17.0, ns). Relative to men, women had higher post
      WTS scores for subjective measures of "nauseous," "dizzy," "nervous," "headache,"
      and "heart pounding." Men and women are exposed to toxicants during WTS, and men
      may achieve higher nicotine exposure than women, likely resulting from
      differences in smoke inhaled. However, similar post-WTS expired air CO between
      men and women and higher ratings of negative subjective responses among women may
      indicate that factors beyond puff topography may impact toxicant exposure and
      subjective response to WTS. (PsycINFO Database Record (c) 2018 APA, all rights
      reserved).

PMID- 30102064
TI  - Examination of posttraumatic stress disorder symptom networks using clinician
      rated and patient-rated data.
AB  - Network theory, which conceptualizes psychiatric disorders as networks of
      interacting symptoms, may provide a useful framework for understanding
      psychopathology. However, questions have arisen regarding the stability and
      generalizability of network analytic methods, with some researchers arguing that
      symptom networks have limited replicability. The aim of this study was to
      evaluate assessment modality as one possible source of instability in the
      estimation of posttraumatic stress disorder (PTSD) symptom networks. We estimated
      two cross-sectional DSM-5 PTSD symptom networks in 378 U.S. veterans: one using
      data from a clinician-rated assessment instrument (Clinician-Administered PTSD
      Scale for DSM-5; CAPS-5) and one using data from a self-rated questionnaire (the
      PTSD Checklist for DSM-5; PCL-5). We calculated centrality indices, conducted
      community structure analyses, and compared the strength and structure of the
      networks. The CAPS-5 and PCL-5 symptom networks were highly similar, challenging
      the notion that network methods produce unreliable results due to estimations
      consisting primarily of measurement error. Furthermore, each network contained
      distinct symptom communities that only partially overlapped with the DSM-5 PTSD
      symptom clusters. These findings may provide guidance for future revisions of the
      DSM, suggest hypotheses about how PTSD symptoms interact, and inform recent
      debate about replicability of psychopathology symptom networks. (PsycINFO
      Database Record

PMID- 30102065
TI  - Stress-induced body dissatisfaction in women with binge eating disorder.
AB  - Stress is known to be a trigger for binge eating in individuals with binge eating
      disorder (BED). However, the influence of stressful situations on BED patients'
      body image is less understood. Our study objective was to gain insight into the
      effects of inducing psychosocial stress on body dissatisfaction in women with
      BED. Overweight women with BED (n = 29) and without an eating disorder (control
      group, CG; n = 38) underwent the Trier Social Stress Test for Groups (TSST-G
      stress) and a nonstressful control task (TSST-G no stress). Additionally, to test
      for the influence of body salience, participants were either exposed or not
      exposed to a mirror. Participants repeatedly rated their current body
      dissatisfaction and psychological distress. Simultaneously, biological stress
      reactivity was measured using salivary cortisol and alpha-amylase (sAA).
      Participants responded to TSST-G stress with significantly higher psychological
      and biological stress compared to the TSST-G control task. The psychological
      distress response was significantly greater in women with BED than the CG. As
      hypothesized, exposure to acute socioevaluative stress led to exacerbated body
      dissatisfaction in the BED group only. The findings of the present study suggest
      that acute socioevaluative stress may play an influential role in BED patients'
      body dissatisfaction. Body image programs might benefit from targeting stress
      management or coping skills in patients with BED. (PsycINFO Database Record

PMID- 30102066
TI  - The valuation of social rewards in schizophrenia.
AB  - Social impairment in schizophrenia is often thought to reflect poor social
      cognition. Here we examine responses to social rewards, an aspect of social
      functioning that is not featured prominently in the literature. The goal of this
      experiment was to explore whether people with schizophrenia (a) undervalue social
      rewards, and (b) whether the undervaluation of social rewards was related to
      motivation and pleasure deficits in schizophrenia and decreased social
      functioning. People with schizophrenia and healthy participants completed a game
      (Shore & Heerey, 2011) to explore preferences for different types of social
      (polite and genuine smiles) and nonsocial (monetary) rewards from computerized
      opponents. Preferences for reward types were quantified for each participant
      based on choice behavior during the game. Participants also completed a smile
      discrimination task to assess their ability to discriminate these types of
      smiles. Analyses revealed that people with schizophrenia (N = 41) treated genuine
      smiles as significantly less rewarding than did healthy participants (N = 29),
      despite showing a similar preference for monetary rewards. The undervaluation of
      social rewards was not related to the ability to discriminate between the smiles.
      The current findings provide preliminary evidence of reduced social reward
      valuation among individuals with schizophrenia, which may have implications for
      behavior in face-to-face social interactions. (PsycINFO Database Record

PMID- 30102068
TI  - Giving and Receiving Effective Feedback: A Review Article and How-To Guide.
AB  - CONTEXT: - Feedback is the delivery of information based on direct observation
      that is meant to improve performance. Learning is at the heart of feedback, and
      as such, feedback is a required competency in pathology resident education. In
      the laboratory setting, the ability of laboratory professionals in all practice
      settings and experience levels to give and receive feedback is crucial to
      workflow and ultimately patient care. OBJECTIVE: - To summarize the importance of
      feedback, strategies for optimizing feedback exchange, and overcoming barriers to
      giving and receiving feedback. DATA SOURCES: - Peer-reviewed original articles,
      review articles, medical education literature, and published books on feedback
      and communication were reviewed to explore ideal methods of giving and receiving
      feedback and to identify common barriers to feedback exchange. CONCLUSIONS: -
      Medical education literature emphasizes techniques for giving feedback and
      describes barriers often encountered to feedback exchange in medical practice.
      Effective feedback requires that the giver, receiver, and environment be
      carefully considered. Likewise, each of these factors can impose barriers to
      feedback exchange. Various methods for giving feedback have been described. All
      feedback should address a specific behavior, be nonevaluative in nature, and be
      followed by confirmation of understanding and an action plan. Few articles
      describe the importance of receiving feedback. Receiving feedback can be
      difficult, but it is enhanced by learning to listen and making conscious
      decisions regarding implementing the messages heard. Giving and receiving
      feedback become easier with practice.

PMID- 30102069
TI  - Challenges in Establishing a Transfusion Medicine Service: The Cleveland Clinic
      Abu Dhabi Experience.
AB  - CONTEXT.-: Opening a new hospital is a once in a lifetime experience and can be
      very inspiring for those involved in its activation. However, establishing a safe
      transfusion practice in a greenfield environment comes with unique challenges and
      opportunities. OBJECTIVE.-: To highlight critical activation components such as
      on-boarding of new personnel, establishing clinical practices, and integrating
      critical laboratory software. DESIGN.-: Our staff initially faced challenges in
      standardizing transfusion medicine clinical practice inside the laboratory. Our
      efforts were mainly focused on the appropriate use of various transfusion orders,
      creating comprehensive policies for type and screening, cost effective
      utilization of blood products, and establishment of the maximum surgical blood
      order schedule. The transfusion service was launched with 2 information
      technology programs that separately facilitated steps in the transfusion process,
      but did not provide centralized access to the entire process. In these
      circumstances, we partnered with the laboratory information system team to create
      a series of interfaces that streamlined each system's functionality and
      implemented the existing infrastructure with upgrades that enable remote location
      and management of blood products. RESULTS.-: The transfusion medicine team spent
      more than a year training and monitoring workflows to avoid individual variations
      between technologists and to adopt our own standards of practice. Participation
      in a structured training plan was also necessary between clinical caregivers to
      know the safe and efficient use of these standards. CONCLUSIONS.-: Although
      laboratory and clinical staff are knowledgeable in care delivery, it is always a
      learning experience to establish a new system because of the natural tendency of
      resorting to previous practices and resistance to new approaches.

PMID- 30102067
TI  - Interoceptive impairments do not lie at the heart of autism or alexithymia.
AB  - Quattrocki and Friston (2014) argued that abnormalities in interoception-the
      process of representing one's internal physiological states-could lie at the
      heart of autism, because of the critical role interoception plays in the ontogeny
      of social-affective processes. This proposal drew criticism from proponents of
      the alexithymia hypothesis, who argue that social-affective and underlying
      interoceptive impairments are not a feature of autism per se, but of alexithymia
      (a condition characterized by difficulties describing and identifying one's own
      emotions), which commonly co-occurs with autism. Despite the importance of this
      debate for our understanding of autism spectrum disorder (ASD), and of the role
      of interoceptive impairments in psychopathology, more generally, direct empirical
      evidence is scarce and inconsistent. Experiment 1 examined in a sample of 137
      neurotypical (NT) individuals the association among autistic traits, alexithymia,
      and interoceptive accuracy (IA) on a standard heartbeat-tracking measure of IA.
      In Experiment 2, IA was assessed in 46 adults with ASD (27 of whom had clinically
      significant alexithymia) and 48 NT adults. Experiment 1 confirmed strong
      associations between autistic traits and alexithymia, but yielded no evidence to
      suggest that either was associated with interoceptive difficulties. Similarly,
      Experiment 2 provided no evidence for interoceptive impairments in autistic
      adults, irrespective of any co-occurring alexithymia. Bayesian analyses
      consistently supported the null hypothesis. The observations pose a significant
      challenge to notions that interoceptive impairments constitute a core feature of
      either ASD or alexithymia, at least as far as the direct perception of
      interoceptive signals is concerned. (PsycINFO Database Record

PMID- 30102070
TI  - Perceptions of Interprofessional and Collaborative Practice in Collegiate
      Athletic Trainers.
AB  - CONTEXT:   The ability to engage in interprofessional and collaborative practice
      (IPCP) has been identified as one of the Institute of Medicine's core
      competencies required of all health care professionals. OBJECTIVE:   To determine
      the perceptions of athletic trainers (ATs) in the collegiate setting regarding
      IPCP and current practice patterns. DESIGN:   Cross-sectional study. PATIENTS OR
      OTHER PARTICIPANTS:   Of 6313 ATs in the collegiate setting, 739 (340 men, 397
      women, 2 preferred not to answer; clinical experience = 10.97 +/- 9.62 years)
      responded (11.7%). MAIN OUTCOME MEASURE(S):   The Online Clinician Perspectives
      of Interprofessional Collaborative Practice survey section 1 assessed ATs'
      perceptions of working with other professionals (construct 1), ATs engaged in
      collaborative practice (construct 2), influences of collaborative practice
      (construct 3), and influences on roles, responsibilities, and autonomy in
      collaborative practice (construct 4). Section 2 assessed current practice
      patterns of ATs providing patient care and included the effect of communication
      on collaborative practice (construct 5) and patient involvement in collaborative
      practice (construct 6). Between-groups differences were assessed using a Kruskal
      Wallis H test and Mann-Whitney U tests ( P < .05). RESULTS:   Athletic trainers
      in the collegiate setting agreed with IPCP constructs 1 through 4 (construct 1 =
      3.56 +/- 0.30, construct 2 = 3.36 +/- 0.467, construct 3 = 3.48 +/- 0.39,
      construct 4 = 3.20 +/- 0.35) and indicated that the concepts of constructs 5 and
      6 (1.99 +/- 0.46, 1.80 +/- 0.50, respectively) were sometimes true in their
      setting. Athletic trainers functioning in a medical model reported lower scores
      for construct 5 (1.88 +/- 0.44) than did those in an athletic model (2.03 +/-
      0.45, U = 19 522.0, P = .001). A total of 42.09% of the ATs' patient care was
      performed in collaborative practice. CONCLUSIONS:   Athletic trainers in the
      collegiate setting agreed that IPCP concepts were beneficial to patient care but
      were not consistently practicing in this manner. Consideration of a medical model
      structure, wherein more regular interaction with other health care professionals
      occurs, may be beneficial to increase the frequency of IPCP.

PMID- 30102071
TI  - Early life influences on child weight outcomes in the Study to Explore Early
      Development.
AB  - We examined associations between child body mass index at 2-5 years and maternal
      pre-pregnancy body mass index, gestational weight gain, and rapid weight gain
      during infancy in children with autism spectrum disorder, developmental delays,
      or population controls. The Study to Explore Early Development is a multi-site
      case-control study of children, aged 2-5 years, classified as autism spectrum
      disorder ( n = 668), developmental delays ( n = 914), or population controls ( n
      = 884). Maternal gestational weight gain was compared to the Institute of
      Medicine recommendations. Rapid weight gain was a change in weight-for-age z
      scores from birth to 6 months > 0.67 standard deviations. After adjusting for
      case status, mothers with pre-pregnancy overweight/obesity were 2.38 times (95%
      confidence interval: 1.96-2.90) more likely, and mothers who exceeded gestational
      weight gain recommendations were 1.48 times (95% confidence interval: 1.17-1.87)
      more likely, to have an overweight/obese child than other mothers ( P < 0.001).
      Children with autism spectrum disorder showed the highest frequency of rapid
      weight gain (44%) and were 3.47 times (95% confidence interval: 1.85-6.51) more
      likely to be overweight/obese as children with autism spectrum disorder without
      rapid weight gain ( P < 0.001). Helping mothers achieve a healthy pre-pregnancy
      body mass index and gestational weight gain represent important targets for all
      children. Healthy infant growth patterns carry special importance for children at
      increased risk for an autism spectrum disorder diagnosis.

PMID- 30102072
TI  - An Assessment of Welfare Conditions in Wildlife Markets across Morocco.
AB  - The welfare of wild-caught animals in markets has generally been overlooked by
      both wildlife trade and welfare studies, despite the potential negative impacts
      on the animals. Morocco is a member of the World Organisation for Animal Health
      and has proposed draft legislation prohibiting mistreatment or abuse of animals
      in captivity. There is still, however, a bustling wild animal trade, and vendor
      compliance with industry-standard best practices is lacking. This study provides
      insight into the conditions of 2113 wild-caught animals in markets in six of the
      largest cities in Morocco by scoring their welfare based on four of the Farm
      Animal Welfare Committee Five Freedoms: freedom from hunger and thirst, freedom
      from discomfort, freedom to express normal behavior, and freedom from distress.
      Over 88% of animals were housed in situations that broke all four of the freedoms
      measured, and only 9 animals were in situations that broke none. Access to water,
      sun/heat exposure, and ability to hide from stressors were particularly poor. We
      urge the Moroccan government to fulfill its commitment to establish welfare laws
      and devote resources to their application.

PMID- 30102073
TI  - Surgical Management of Madelung Deformity: A Systematic Review.
AB  - BACKGROUND: Madelung deformity is a congenital wrist condition characterized by
      volar subluxation of the wrist caused by premature growth arrest of the distal
      radius. Progressive symptoms can necessitate surgical intervention, yet optimal
      treatment strategy remains unknown. The aim of this study is to determine
      treatment options, surgical indications, and operative outcomes for Madelung
      deformity. METHODS: This study adhered to the Meta-Analyses of Observational
      Studies in Epidemiology (MOOSE) guidelines. A comprehensive systematic review was
      performed to identify all studies describing surgical interventions for Madelung
      deformity. All studies were evaluated by level of evidence and a self-developed
      quality assessment tool. RESULTS: Twenty-five studies met inclusion criteria; all
      case series with type IV level of evidence. Studies assessed pain, range of
      motion, aesthetic deformity, and grip strength. The primary indication for
      surgery was the presence of wrist pain. Various surgical procedures exist and
      could be categorized as radial lengthening, ulnar shortening, or a combination of
      both. All studies report postoperative pain reduction and most studies report an
      improved range of motion. CONCLUSIONS: A variety of surgical procedures
      reportedly have satisfactory outcomes. However, outcomes are reported in an
      inconsistent manner, prohibiting pooling of studies and comparisons of surgical
      procedures and their outcomes. We propose several methodological changes for
      implementation in future studies, increasing the quality of evidence to
      compensate for small patient numbers.

PMID- 30102074
TI  - Oxidative stress contribution to attention deficit hyperactivity disorder in
      children with epilepsy.
AB  - Children with epilepsy have a high incidence of attention deficit hyperactivity
      disorder (ADHD). Oxidation stress and disturbed neurotransmitters are suggested
      mechanisms; however, their role is not fully explored. This study evaluates the
      association between circulating malondialdehyde as an oxidation stress marker,
      apelin neuropeptide, and ADHD in children with epilepsy. Fifty children with
      epilepsy of unknown etiology, of which 25 have ADHD, as well as 35 healthy
      children were included. Serum levels of malondialdehyde and apelin were
      estimated. We investigated the association between seizure severity, response to
      medications, malondialdehyde, apelin levels, and ADHD in children with epilepsy.
      Serum malondialdehyde and apelin levels were higher in children with epilepsy,
      especially those with ADHD. Malondialdehyde and apelin levels have significant
      positive correlation with the Chalfont Seizure Severity Score. Regression
      analysis showed that elevated malondialdehyde is an independent risk factor for
      ADHD in children with epilepsy (OR: 1.401, 95%CI: 1.056-1.859, p= 0.02). No
      significant association was found between malondialdehyde and apelin levels and
      the type of epilepsy or ADHD. Longer duration of epilepsy, increased seizure
      severity, and uncontrolled seizures are associated with increased oxidation
      stress, which further increased susceptibility for ADHD. In spite of elevated
      apelin in children with ADHD, the elevation did not increase the risk of ADHD in
      children with epilepsy.

PMID- 30102075
TI  - A cross-sectional study in young adults with psoriasis: potential determining
      factors in quality of life, life course and work productivity.
AB  - BACKGROUND: Psoriasis can have a substantial impact on health-related quality of
      life (HRQoL), life course, and work productivity. Young adulthood is a critical,
      sensitive period of development that includes major life changing decisions. The
      impact of psoriasis on this vulnerable population is yet unknown. OBJECTIVES: To
      assess QoL, life course, and work productivity in young adults with psoriasis and
      identify characteristics influencing these patient-reported outcomes (PRO).
      METHODS: An explorative, cross-sectional study was performed in psoriasis
      patients aged 18-30 years. Individuals completed a set of questionnaires
      regarding their health status (DLQI, SF-36, EQ-5D), achievement of developmental
      milestones (COLQ), and work productivity (WPAI-PSO, PRODISQ). RESULTS: Seventy
      five patients (22 males, 53 females; median age [IQR], 21.0 [8.0]). Median PASI
      and BSA, respectively, were 4.4 [4.9] and 4.5 [8.4]. Young adults experienced
      feelings of embarrassment, impairments in physical health and work productivity,
      and difficulties in social development. Patients with more severe psoriasis,
      longer disease duration, higher body mass index (BMI), female patients and
      patients closer to their thirties tended to be more affected. CONCLUSION: In the
      young adult psoriasis population, substantial QoL impairments were found. Female
      patients, patients with high BMI, or long disease duration in particular tended
      to experience more difficulties. These exploratory findings indicate the need for
      further studies in young adults to detect potential clinical predictors for
      severe HRQoL impairments.

PMID- 30102077
TI  - Metrics of Survival: Post-Abortion Care and Reproductive Rights in Senegal.
AB  - Drawing on ethnographic fieldwork conducted in Senegal between 2010 and 2011, I
      demonstrate how health professionals have deployed indicators such as number of
      women and abortion type treated in government hospitals to demonstrate commitment
      to global mandates on reproductive rights. These indicators obscure
      discrimination against women suspected of illegal abortion as health workers
      negotiate obstetric treatment with the abortion law. By measuring hospitals'
      capacity to keep women with abortion complications alive, post-abortion care
      (PAC) indicators have normalized survival as a state of reproductive well-being.

PMID- 30102076
TI  - Strategic development of AZD1775, a Wee1 kinase inhibitor, for cancer therapy.
AB  - INTRODUCTION: Wee1 kinase controls the G2-M checkpoint. Wee1 inhibition by
      AZD1775 allows cells with a deregulated G1 checkpoint to progress, resulting in
      catastrophe and apoptosis. The challenges ahead are in the establishment of the
      optimum dosing schedule either alone or in combination and the identification of
      patients with specific biomarker profiles who benefit most. Areas covered: This
      article provides an overview of AZD1775, based on English peer-reviewed articles
      on MEDLINE. The authors highlight the data from the published preclinical and
      clinical studies. Expert opinion: A majority of the current clinical trials focus
      on AZD1775 combined with chemotherapy or radiation. Treatment with AZD1775 was
      tolerated, and antitumor activity has been observed, especially in patients with
      advanced malignancies harboring G1 checkpoint aberrations and/or DNA damage
      repair defects. Thus, identification of the molecular subtypes that benefit most
      from the treatment with AZD1775 alone or in combination may provide a novel
      strategy for cancer therapy. Research is needed for devising regimens to explore
      AZD1775 in combination with biologically targeted agents and/or immunotherapy
      (low dose vs. high dose, intermittent vs. continuous, sequential vs. concurrent,
      etc.) for identifying potential biomarkers predictive of response and survival.

PMID- 30102078
TI  - Efficacy, tolerability, and safety of serotonergic psychedelics for the
      management of mood, anxiety, and substance-use disorders: a systematic review of
      systematic reviews.
AB  - INTRODUCTION: Mood, anxiety, and substance-use disorders are among the most
      prevalent psychiatric disorders in the population. Although several
      pharmacological treatments are available, they are not effective for a
      significant proportion of patients and are associated with several adverse
      reactions. Therefore, new treatments should be explored. Recent studies suggest
      that serotonergic hallucinogens/psychedelics including ayahuasca, psilocybin, and
      lysergic acid diethylamide (LSD) have anxiolytic, antidepressive, and
      antiaddictive effects. Areas Covered: A systematic review of systematic reviews
      assessing the efficacy, safety, and tolerability of serotonergic
      hallucinogens/psychedelic was performed using the PubMed data base until 11 April
      2018. Systematic reviews with or without meta-analysis were analyzed, but only
      reviews that described at least one randomized controlled trial (RCT) were
      included. Expert Commentary: Psilocybin and LSD reduced anxiety and depression in
      cancer patients and symptoms of alcohol and tobacco dependence, and ayahuasca
      reduced depression symptoms in treatment-resistant depression. Although the
      results are promising, several studies were open label, and only few were RCTs,
      and most had small sample sizes and a short duration. Single or few doses of
      these drugs seem to be well tolerated, but long-term studies are lacking. New
      RCTs with bigger samples and longer duration are needed to replicate these
      findings.

PMID- 30102080
TI  - Determination of precipitation inhibitory potential of polymers from amorphous
      solid dispersions.
AB  - : Precipitation inhibitory potential of polymers screened from precipitation
      study may be altered once it is formulated in amorphous solid dispersions (ASDs).
      OBJECTIVE: Present study was embarked with an objective to determine whether the
      polymers retain the same inhibitory potential after formulating them into ASDs.
      METHODS: Screening of polymers was based on a new dimensionless parameter
      'Supersaturation Holding Capacity (SHC)' calculated from the precipitation study.
      Nifedipine ASDs were formulated using HPMC E3 and HPMC E50 (high SHC values), and
      HPMC K100M, PVP K25, and HPC M (low to moderate SHC values). Generated ASDs were
      characterized by DSC, FTIR, and PXRD and evaluated for stability under
      accelerated conditions (40C and 75% RH) for 6 months. RESULTS: Thermal analysis
      of the ASDs and theoretical prediction of the glass transition temperature (Tg)
      suggested a linear dependency of Tg on the content of HPMC E3 and HPMC E50. Under
      accelerated stability conditions, all ASDs of nifedipine with HPMC E3 and HPMC
      E50 (except ASDs with 70% drug load) were stable, which could be attributed to
      the molecular level dispersion of the drug in these polymers. SHC parameter
      calculated from the apparent solubility profile gave following rank order HPMC
      E50 (3.4) > HPMC E3 (3.2) > HPMC K100M (1.29) > PVP K25 (1.09) > HPC M (0.99).
      SHC calculated from the apparent solubility profile of ASDs demonstrated good
      agreement between the solution state and solid state screening of the polymers
      for precipitation inhibition. During dissolution study, nearly four-fold
      enhancement has been observed with ASDs comprising HPMC E3 and HPMC E50.
      CONCLUSIONS: The outcome of the study concluded that SHC can be a promising
      parameter in the screening of polymers for the development of the ASDs.

PMID- 30102079
TI  - Using antipsychotics for behavioral problems in children.
AB  - INTRODUCTION: Antipsychotic use in children has increased over the past two
      decades. Randomized controlled trials have evaluated the efficacy of
      antipsychotics in autism spectrum disorder (ASD) and disruptive behavior
      disorders (DBD). Areas covered: The authors systematically analyze the results of
      randomized controlled trials of second and third generation antipsychotics for
      irritability in ASD and aggressive and disruptive behavior in DBD with or without
      low IQ and ADHD. The aim of the review is to assist healthcare professionals to
      optimize therapy in this population. Expert opinion: There is evidence to support
      the short-term efficacy of risperidone and aripiprazole for irritability in ASD,
      and short-term efficacy of risperidone for aggressive and disruptive behavior in
      DBD, although the benefits are closely balanced with an increased risk of
      metabolic, hormonal and extrapyramidal adverse effects. The use of antipsychotics
      in children with these disorders should be reserved for those refractory to first
      and second-line therapies, and in whom there is a persistent and serious risk of
      harm to self or others. Antipsychotics should be considered a short-term strategy
      while psychosocial and behavioral therapies are continuously employed.

PMID- 30102081
TI  - Psychedelics as anti-inflammatory agents.
AB  - Serotonin (5-hydroxytryptamine, 5-HT)2A receptor agonists have recently emerged
      as promising new treatment options for a variety of disorders. The recent success
      of these agonists, also known as psychedelics, like psilocybin for the treatment
      of anxiety, depression, obsessive-compulsive disorder (OCD), and addiction, has
      ushered in a renaissance in the way these compounds are perceived in the medical
      community and populace at large. One emerging therapeutic area that holds
      significant promise is their use as anti-inflammatory agents. Activation of 5
      HT2A receptors produces potent anti-inflammatory effects in animal models of
      human inflammatory disorders at sub-behavioural levels. This review discusses the
      role of the 5-HT2A receptor in the inflammatory response, as well as highlight
      studies using the 5-HT2A agonist (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI] to
      treat inflammation in cellular and animal models. It also examines potential
      mechanisms by which 5-HT2A agonists produce their therapeutic effects. Overall,
      psychedelics regulate inflammatory pathways via novel mechanisms, and may
      represent a new and exciting treatment strategy for several inflammatory
      disorders.

PMID- 30102082
TI  - Therapeutic use of classic psychedelics to treat cancer-related psychiatric
      distress.
AB  - Cancer is highly prevalent and one of the leading causes of global morbidity and
      mortality. Psychological and existential suffering is common in cancer patients,
      associated with poor psychiatric and medical outcomes. Promising early-phase
      clinical research (1960s to early 1970s) suggested a therapeutic signal for
      serotoninergic psychedelics (e.g. psilocybin, LSD) in treating cancer-related
      psychiatric distress. After several decades of quiescence, research on
      psychedelic-assisted therapy to treat psychiatric disorders in cancer patients
      has resumed within the last 2 decades in the US and Europe. This review article
      is based on a systematic search of clinical trials from 1960-2018 researching the
      therapeutic use of psychedelic treatment in patients with serious or terminal
      illnesses and related psychiatric illness. The search found 10 eligible clinical
      trials, with a total of 445 participants, with the vast majority of the patients
      having advanced or terminal cancer diagnoses. Six open label trials, published
      between 1964 and 1980 (n = 341), suggested that psychedelic therapy (mostly with
      LSD) may improve cancer-related depression, anxiety, and fear of death. Four RCTs
      trials were published between 2011 and 2016 (n = 104), mostly with psilocybin
      treatment (n = 92), and demonstrated that psychedelic-assisted treatment can
      produce rapid, robust, and sustained improvements in cancer-related psychological
      and existential distress.

PMID- 30102083
TI  - Cangrelor for the treatment of patients with Arterial Thrombosis.
AB  - INTRODUCTION: All oral P2Y12 receptor blockers are associated with some degree of
      delayed onset and offset of pharmacodynamic (PD) effects in patients with acute
      coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI).
      Although intravenous glycoprotein IIb/IIIa inhibitors are associated with rapid
      onset of action, they are also associated with delayed offset and other
      limitations such as elevated bleeding risk and thrombocytopenia. Areas covered:
      In this review, the authors focus on cangrelor, an intravenous, reversible P2Y12
      receptor blocker with fast onset and offset of effects. The authors also describe
      the pharmacologic effects of cangrelor and its pharmacologic interaction with
      other P2Y12 receptor inhibitors. Finally, the authors discuss the large-scale
      clinical trials that compared the efficacy and safety of cangrelor with
      clopidogrel. Expert opinion: In ACS patients undergoing PCI, cangrelor is most
      desirable to effectively prevent periprocedural ischemic events and to avoid
      excessive bleeding. Indeed, any high-risk patient with ST-segment elevation
      myocardial infraction or patient who is unable to take oral medications is a
      potential candidate for intravenous cangrelor therapy. Furthermore, stable
      patients with coronary artery disease, who are considered for ad hoc PCI
      following coronary angiography, may be considered for treatment with cangrelor to
      reduce post-PCI thrombotic events.

PMID- 30102084
TI  - Morphophonology and compensation in Specific Language Impairment: Evidence from
      Standard Modern Greek and Cypriot Greek.
AB  - The current study investigates the role of the morphophonological realisation of
      grammatical features as a compensatory mechanism for morphosyntactic deficits in
      specific language impairment (SLI). The phenomenon examined is past tense
      formation in Standard Modern Greek (SMG) and Cypriot Greek (CG) as it manifests a
      distinction in morphophonological salience realisation in the two linguistic
      varieties via differential use of a stress shift and stressed syllabic augment
      [e] required for past tense rule formation. Participants were pre-schoolers with
      typical language development (TD) and children with SLI. Subjects produced real
      verb (RV) and pseudo-verb stimuli (PV) in sentence completion tasks. Results
      indicated that morphophonological properties of past tense formation affected SLI
      but not TD performance. We attribute the results to the difference in the status
      of the augment in each variety and the effects it has on its realisation at the
      phonetic interface. Furthermore, verb contractibility appeared to pose particular
      difficulties in the performance of all groups.

PMID- 30102085
TI  - Evaluation of miniscrew-supported rapid maxillary expansion in adolescents: A
      prospective randomized clinical trial.
AB  - OBJECTIVES:: To evaluate and compare the dental and skeletal changes with
      conventional and miniscrew-supported maxillary expansion appliances in
      adolescents. MATERIALS AND METHODS:: Forty patients were divided into two groups,
      with one group receiving a tooth-borne expander and the other group receiving an
      expander supported by four miniscrews (bone-borne). Multiplanar coronal and axial
      slices obtained from cone-beam computed tomography images were used to measure
      the changes in transverse skeletal widths, buccal bone thickness, tooth
      inclination, and root length. Paired t-tests and independent-sample t-tests were
      used to compare the two expansion methods. RESULTS:: Bone-borne expansion
      increased the maxillary suture opening more than 2.5 times than tooth-borne
      expansion both anteriorly and posteriorly. Between the maxillary first premolars,
      sutural expansion accounted for 28% and 70% of the total transverse width
      increase in the tooth-borne and bone-borne expander groups, respectively.
      Similarly, 26% and 68% of the total expansion was of skeletal nature in the tooth
      borne and bone-borne expander groups between the maxillary first molars. The
      pattern of expansion was variable, with most of the patients in both groups
      demonstrating a triangular-shaped sutural opening that was wider anteriorly.
      Subjects in the conventional group experienced significantly more buccal bone
      reduction and greater buccal inclination of the teeth. No significant differences
      were observed for root length measurements between the two groups. CONCLUSION::
      Use of bone-borne expansion in the adolescent population increased the extent of
      skeletal changes in the range of 1.5 to 2.8 times that of tooth-borne expansion
      and did not result in any dental side effects.

PMID- 30102086
TI  - The 100 most-cited articles in orthodontics: A bibliometric study.
AB  - OBJECTIVES:: To identify and analyze the 100 most-cited articles in orthodontics
      indexed in the Web of Science Category of "Dental, Oral Surgery and Medicine"
      from 1946 to 2016. MATERIALS AND METHODS:: On hundred articles were identified in
      a search of the database of the ISI Web of Science and Journal Citation Reports,
      applying the truncated search term "orthodon*." Records were manually refined and
      normalized to unify terms and to remove typographical, transcription, and/or
      indexing errors. RESULTS:: The 100 most-cited articles were published between
      1946 and 2012, with numbers of citations ranging from 115 to 881. Of the 251
      authors participating, 87.65% published a single work, while three authors
      published four works. Most of the authors with several citations were from the
      United States, although the University of Oslo produced the highest number of
      frequently cited works. Most of the articles were clinical studies, and the most
      frequently cited topic was mini-implants. It was noted that self-citation could
      be a potential cause of bias in bibliometric analysis. CONCLUSIONS:: This
      bibliometric citation analysis reveals new, useful, and interesting information
      about scientific progress in the field of orthodontics.

PMID- 30102087
TI  - Association between maxillary lateral incisors' root volume and palatally
      displaced canines: An instrumental variables approach to the guidance theory.
AB  - OBJECTIVES:: To evaluate association and causation between maxillary lateral
      incisors' (MxI2) apical root volume (ARV) and palatally displaced canines (PDC).
      MATERIALS AND METHODS:: In a retrospective cross-sectional study, computed
      tomography scans of 179 patients with unilateral PDC were analyzed. MxI2 root
      length and volume on the impaction and eruption side were measured. A mixed logit
      model was used to infer the association between ARV and PDC and an instrumental
      variables approach to interpret causality. RESULTS:: MxI2 root length on the
      impaction side was shorter in 42%, equal in 33% and longer in 25% of the
      patients. ARV amounted for 13.5% of total root volume on the impaction and 14.9%
      on the eruption side. Reduced ARV was significantly associated with the impaction
      side ( P < .001). The causal effect of ARV on PDC in the instrumental variable
      approach amounted to less than half of the association in a standard noncausal
      approach. CONCLUSIONS:: An association between PDC and reduced MxI2 root length
      and volume was confirmed. However, the lack of causality did not allow the
      researchers to draw a conclusion as to whether a reduced ARV is causing PDC or
      resulting from it; this should be considered in etiologic theories.

PMID- 30102088
TI  - Space conditions, palatal vault height, and tooth size in patients with and
      without palatally displaced canines: A prospective cohort study.
AB  - OBJECTIVES:: To assess palatal vault height, tooth size, and dental arch
      dimensions in patients with unilateral and bilateral palatally displaced canines
      compared with a control group. MATERIALS AND METHODS:: A sample of 66 patients
      (mean age: 11.5 +/- 1.0 years) with 22 unilateral palatally displaced canines
      (UPDCs), 22 bilateral palatally displaced canines (BPDCs), and 22 controls (C)
      were consecutively recruited. All three groups had dental casts that were scanned
      digitally using the OrthoX three-dimensional model scanner. Tooth size, palatal
      vault height, dental arch width, dental arch depth, dental arch length, and
      dental arch space were measured by the same examiner using the GOM software.
      Remeasurements were made in 10 randomly identified patients. RESULTS:: The
      palatal vault height was significantly lower in the BPDC group compared with
      controls. A significantly smaller mesial-distal crown width and, in general, more
      spacing in the maxilla were found in the UPDC and BPDC groups. No differences in
      arch length or arch width at the molar region were seen between the groups, while
      the arch length at the canine region was smaller in the UPDC and BPDC groups.
      However, this was observed in BPDC patients with both deciduous canines present
      and in most UPDC patients where the deciduous canine was present, compared with
      the control group, who had more permanent canines present. CONCLUSIONS:: Patients
      with PDC had greater reduction in tooth size compared with the control group. The
      arch length and arch width were similar in patients with and without PDC.

PMID- 30102089
TI  - The association between circadian rest-activity patterns and the behavioral and
      psychological symptoms depending on the cognitive status in Japanese nursing-home
      residents.
AB  - BACKGROUND: Limited information is available on the relationship between sleep
      disturbances during nighttime and the behavioral and psychological symptoms of
      dementia in older nursing-home residents. However, a few reports on the
      association between the circadian rest-activity rhythm and the behavioral and
      psychological symptoms of dementia in older residents have been published. The
      main objective of the present study was to examine the association among the
      circadian rest-activity rhythm, behavioral and psychological symptoms, and the
      cognitive function status among older individuals living in facilities. METHOD:
      The investigation was conducted from September 2017 to February 2018, and
      participants were recruited from five nursing homes in Akita prefecture, Japan,
      after obtaining patient agreement to participate in the study. To measure
      nonparametric circadian rest-activity parameters such as interdaily stability,
      intradaily variability, relative amplitude, mean of the least active 5-h period,
      and mean of the most active 10-h period, Actigraph devices were worn on the
      participants' nondominant wrists continuously for seven days. The score or
      classification of the cognitive status and the severity of the behavioral and
      psychological symptoms of dementia (BPSD) were assessed using the clinical
      dementia rating (CDR) and the dementia behavior disturbance scale (DBD),
      respectively. The binomial logistic regression model was applied to clarify which
      kinds of circadian rest-activity parameters predicted the cognitive status in
      nursing home residents as well as the BPSD outcome. A multi-level model was also
      used to examine the association between the nonparametric rest-activity
      parameters and the BPSD outcome explained by the cognitive status among older
      individuals in facilities. RESULTS: Seventy-seven participants (49 residents with
      dementia, and 28 residents without dementia) were included in this study.
      According to the binomial logistic regression analysis after adjusting for
      covariates, the classification of the cognitive status for older residents was
      associated with the DBD score (odds ratio, 1.22; 95% confidence interval [CI],
      1.08, 1.38; p < 0.001), the IS (odds ratio, 0.01; 95% CI, 0.00, 1.00; p = 0.05)
      and the L5 (odds ratio, 0.99; 95% CI, 0.99, 1.00; p = 0.05). The results of a
      multi-level model also indicated that the IV at individual-level was
      significantly associated with the DBD score for nursing home residents, with the
      CDR score at cluster-level as an explanatory variable. As well, a significant
      association between the RA at individual level and the DBD score was observed in
      a multi-level model explained by the CDR score at cluster-level. CONCLUSION: Of
      these models, the multi-level model provided grounds for our proposal that the
      fragmentation or the amplitude of rest-activity parameters might be associated
      with the outcome of BPSD, considering the cognitive status of older individuals
      in different facilities. The findings offer practical insight into the prevention
      of BPSD and the improvement of rest-activity rhythms in rehabilitative care in
      nursing homes.

PMID- 30102090
TI  - Scott Reeves: 1967-2018.

PMID- 30102091
TI  - MLLT10 promotes tumor migration, invasion, and metastasis in human colorectal
      cancer.
AB  - OBJECTIVES: Colorectal cancer (CRC), one of the most aggressive gastrointestinal
      malignancies, is a frequently diagnosed life-threatening cancer worldwide. Most
      CRC patients have poor prognosis mainly because of frequent metastasis and
      recurrence. Thus, it is crucial to find out some new biomarkers and to show
      deeper insights into the mechanisms of CRC. MLLT10, Myeloid/lymphoid or mixed
      lineage leukemia translocated to 10, also known as AF10, a recurrent MLL partner.
      In this study, we found that MLLT10 promotes CRC tumor invasion and metastasis
      both in vitro and in vivo. METHODS: Here, the expression of MLLT10 was evaluated
      by immunohistochemistry. Then, the plasmid and lentivirus particles for MLLT10
      overexpression or knockdown were designed and constructed into SW620 and HT29
      cells. Finally, cell proliferation assay, cell adhesion assay, transwell
      migration, and invasion assay were used to detect the migration and invasion
      ability of MLLT10 in CRC cells. A tail vein injection assay was employed to
      evaluate the role of MLLT10 in tumor metastases. RESULTS: MLLT10 expression was
      significantly higher in CRC tissues than in noncancerous tissues and was
      associated with some clinicopathological factors. In vitro, the overexpression of
      MLLT10 promoted CRC cell migration and invasion, while after MLLT10 was knocked
      down, the opposite results were observed. Furthermore, we used animal metastasis
      models to detect the function of MLLT10 in vivo, the results are same with the
      outcomes in vitro. In lung metastasis sites, the knockdown of MLLT10 in SW620
      cells significantly inhibited Vimentin expression, whereas the E-Cadherin was
      increased. CONCLUSIONS: These results indicate that MLLT10 regulates the
      metastasis of CRC cells via EMT.

PMID- 30102092
TI  - Effect of omega-3 supplements on plasma apolipoprotein C-III concentrations: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Apolipoprotein C-III (apo C-III) is a key regulator of triglycerides
      metabolism. The aim of this meta-analysis was to assess the effect of fish omega
      3 polyunsaturated fatty acids (PUFAs) on apo C-III levels. METHODS: Randomized
      placebo-controlled trials investigating the impact of omega-3 on apo C-III levels
      were searched in PubMed-Medline, SCOPUS, Web of Science and Google Scholar. A
      random-effects model and generic inverse variance method were used for
      quantitative data synthesis. Sensitivity analysis was conducted using the leave
      one-out method. A weighted random-effects meta-regression was performed to
      evaluate the impact of potential confounders on glycemic parameters. RESULTS:
      This meta-analysis comprising 2062 subjects showed a significant reduction of apo
      C-III concentrations following treatment with omega-3 (WMD: -22.18 mg/L, 95%
      confidence interval: -31.61, -12.75, p < .001; I2: 88.24%). Subgroup analysis
      showed a significant reduction of plasma apo C-III concentrations by
      eicosapentaenoic acid (EPA) ethyl esters but not omega-3 carboxylic acids or
      omega-3 ethyl esters. There was a greater apo C-III reduction with only EPA as
      compared with supplements containing EPA and docosahexaenoic acid (DHA) or only
      DHA. A positive association between the apo C-III-lowering effect of omega-3 with
      baseline apo C-III concentrations and treatment duration was found. CONCLUSIONS:
      This meta-analysis has shown that omega-3 PUFAs might significantly decrease apo
      C-III. Key messages Omega-3 PUFA supplements significantly reduce apo C-III
      plasma levels, particularly in hypertriglyceridemic patients when applied in
      appropriate dose (more than 2 g/day) Triglyceride (TG)-lowering effect is
      achieved via peroxisome proliferator-activated receptors alpha Further studies
      should address the effect of omega-3 PUFAs alone or with other lipid-lowering
      drugs in order to provide a final answer whether apo C-III could be an important
      target for prevention of cardiovascular disease New apo C-III antisense
      oligonucleotide drug (Volanesorsen) showed to be promising in decreasing elevated
      TGs by reducing levels of apo C-III mRNA.

PMID- 30102093
TI  - Analysing health data sources to inform chronic disease management decisions of
      health insurers: A mixed methods study.
AB  - BACKGROUND AND OBJECTIVE: Both health care providers and payers recognize the
      need to improve chronic disease care. Chronic disease management relies on high
      quality health information for people with, and at risk of developing, chronic
      diseases. This article focuses on the health insurance sector and investigates
      ways that payment claims data and other data sources can provide useful
      information to support chronic disease management interventions. METHODS AND
      RESULTS: In this mixed methods study, we first examine methods of selecting
      target populations from insurance claims data for common chronic conditions
      diabetes, cardiovascular disease, and mental health disorders. The analysis of
      claims data reveals data quality issues and indicates that other data sources
      should be considered to provide additional information. We undertake a
      qualitative review of factors influencing the development of information systems
      for chronic disease management that use multiple data sources. CONCLUSIONS:
      Claims data should be supplemented with other data to inform chronic disease
      management. The article proposes a conceptual framework with four domains that
      need to be considered when developing chronic disease information systems using
      multiple data sources-information requirements, data sources, data collection,
      and information systems integration. There are policy and organizational factors
      that influence framework implementation.

PMID- 30102094
TI  - A three-step methodology for process-oriented performance: how to enhance
      automated data collection in healthcare.
AB  - BACKGROUND: Healthcare managers often attempt to enhance process-oriented
      performance. However, this remains a challenge. New approaches aimed at
      increasing the implementation success of process-oriented performance measurement
      should be investigated. METHODS: This study investigates and discusses a step-by
      step methodology to implement an automated and effective process-oriented
      performance measurement system in a hospital. The methodology is based on a
      framework for developing dashboards based on three steps: the demand side, supply
      side, and the fit between the two. An illustrative case of the process of hip
      surgery in the operating room of two hospitals is used. RESULTS: A methodology
      has been developed to define a reliable set of process-oriented performance
      metrics, allowing analysis and management of the different flows in healthcare in
      an integrated way, several methods were investigated to automatically integrate
      the data gathered into a reporting infrastructure that can be used to disseminate
      the results. CONCLUSION: This step-by-step methodology allows healthcare
      organizations to develop and implement effective process-oriented performance
      measurement in an automated way. This allows the alignment of the goals of
      hospital management and various stakeholders with the more analytical analysis of
      business process management notation and hospital information system (HIS) data.

PMID- 30102095
TI  - Automatic measurement of fall risk indicators in timed up and go test.
AB  - Fall risk assessment is usually conducted in specialized centers using clinical
      tests. Most of the time, these tests are performed only after the occurrence of
      health problems potentially affecting gait and posture stability. Our aim is to
      define fall risk indicators that could routinely be used at home to automatically
      monitor the evolution of fall risk over time. We used the standard Timed Up and
      Go (T.U.G.) test to classify 43 individuals into two classes of fall risk, namely
      high- vs low- risk. Several parameters related to the gait pattern and the
      sitting position included in the T.U.G. test were automatically extracted using
      an ambient sensor (Microsoft Kinect sensor). We were able to correctly classify
      all individuals using machine learning on the combination of two parameters among
      gait speed, step length and speed to sit down. Coupled to an ambient sensor
      installed at home to monitor the relevant parameters in daily activities, these
      algorithms could therefore be used to assess the evolution of fall risk, thereby
      improving fall prevention.

PMID- 30102097
TI  - Apolipoprotein E polymorphism and age-related macular degeneration.

PMID- 30102096
TI  - The Influence of Race and Sex on the Side Effect Profile of Methotrexate in the
      Treatment of Uveitis.
AB  - PURPOSE: To detect any correlation between race and sex and the side effects of
      methotrexate in uveitis treatment. METHODS: Retrospective review of patients seen
      at Northwestern Memorial Hospital between August 2012 and September 2014 with a
      history of MTX treatment for uveitis. Demographic, treatment, and side-effect
      data were collected for each patient. RESULTS: Ninety-seven patients were
      included (25 males, 72 females). Twenty-eight patients reported African American
      race, 60 reported Caucasian race, and the remaining 9 reported Asian, Hispanic,
      or Arabic ethnicity. Males experienced more gastrointestinal upset than females
      (24% versus 13.8%). Caucasians had more gastrointestinal complaints (20% versus
      8%) while African Americans developed more hair loss (14% versus 6.6%), although
      the numbers were too small to detect a statistical difference. CONCLUSION: While
      our sample was small, these findings suggest racial and gender disparities in the
      side effects experienced by patients treated with methotrexate. This information
      may be useful to clinicians counseling patients on risk profile.

PMID- 30102098
TI  - A brief history of clinical evidence updates and bibliographic databases.

PMID- 30102103
TI  - A giant step for science: JRSM welcomes preprints in medical science.

PMID- 30102100
TI  - The strengths of general practice.

PMID- 30102104
TI  - Administration of testosterone improves the prothrombotic and antifibrinolytic
      parameters associated with its deficiency in an orchidectiomized rat model.
AB  - This study investigated the effect of testosterone deficiency and replacement on
      platelets function and aggregation, coagulation, and fibrinolysis in young adult
      healthy male rats. Rats were classified into three groups (n = 6/group) of either
      "a sham-operated+ vehicle," "an orchidectomized (ORX)+ vehicle," and "an
      ORX+testosterone propionate (0.5 mg/kg, 3X/week, S.C)." All treatments were
      carried out for 12 weeks. Our results showed that ORX rats had induced platelets
      aggregation and coagulation and inhibited fibrinolysis. ORX-induced rats had
      increased ratios of adenosine diphosphate-induced aggregation, shorter bleeding
      time, clotting time, prothrombin time, and activated partial thromboplastin time
      and their sera showed increased levels of thromboxane B2 and fibrinogen levels.
      Concomitantly, their plasma showed increased TPA-1 and decreased tissue
      plasminogen activator (tPA) levels. At molecular levels, the aorta of ORX-induced
      rats showed increased aortic mRNA and protein levels of plasminogen activator
      inhibitor-1 (PAI-1), protein levels of von Willebrand Factor (vWF) and decreased
      mRNA and protein levels of tPA, and their liver showed increased protein levels
      of prothrombin and factor VII. Testosterone post-therapy to ORX-induced rats
      significantly reversed all these hematological and molecular changes. In
      conclusion, independent of any other risk factors, testosterone deficiency
      induces platelets aggregation and hypercoagulation and inhibits fibrinolysis,
      effects that can be reversed by testosterone therapy.

PMID- 30102106
TI  - Effects of inter-character spacing on saccade programming in beginning readers
      and dyslexics.
AB  - The present study investigated the impact of inter-character spacing on saccade
      programming in beginning readers and dyslexic children. In two experiments, eye
      movements were recorded while dyslexic children, reading-age, and chronological
      age controls, performed an oculomotor lateralized bisection task on words and
      strings of hashes presented either with default inter-character spacing or with
      extra spacing between the characters. The results of Experiment 1 showed that (1)
      only proficient readers had already developed highly automatized procedures for
      programming both left- and rightward saccades, depending on the discreteness of
      the stimuli and (2) children of all groups were disrupted (i.e., had trouble to
      land close to the beginning of the stimuli) by extra spacing between the
      characters of the stimuli, and particularly for stimuli presented in the left
      visual field. Experiment 2 was designed to disentangle the role of inter
      character spacing and spatial width. Stimuli were made the same physical length
      in the default and extra-spacing conditions by having more characters in the
      default spacing condition. Our results showed that inter-letter spacing still
      influenced saccade programming when controlling for spatial width, thus
      confirming the detrimental effect of extra spacing for saccade programming. We
      conclude that the beneficial effect of increased inter-letter spacing on reading
      can be better explained in terms of decreased visual crowding than improved
      saccade targeting.

PMID- 30102107
TI  - First Report of Powdery Mildew Caused by Golovinomyces orontii on Campanula
      glomerata in Italy.

PMID- 30102105
TI  - Structural investigation of human S. aureus-targeting antibodies that bind wall
      teichoic acid.
AB  - Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a
      growing health threat worldwide. Efforts to identify novel antibodies that target
      S. aureus cell surface antigens are a promising direction in the development of
      antibiotics that can halt MRSA infection. We biochemically and structurally
      characterized three patient-derived MRSA-targeting antibodies that bind to wall
      teichoic acid (WTA), which is a polyanionic surface glycopolymer. In S. aureus,
      WTA exists in both alpha- and beta-forms, based on the stereochemistry of
      attachment of a N-acetylglucosamine residue to the repeating phosphoribitol sugar
      unit. We identified a panel of antibodies cloned from human patients that
      specifically recognize the alpha or beta form of WTA, and can bind with high
      affinity to pathogenic wild-type strains of S. aureus bacteria. To investigate
      how the beta-WTA specific antibodies interact with their target epitope, we
      determined the X-ray crystal structures of the three beta-WTA specific
      antibodies, 4462, 4497, and 6078 (Protein Data Bank IDs 6DWI, 6DWA, and 6DW2,
      respectively), bound to a synthetic WTA epitope. These structures reveal that all
      three of these antibodies, while utilizing distinct antibody complementarity
      determining region sequences and conformations to interact with beta-WTA, fulfill
      two recognition principles: binding to the beta-GlcNAc pyranose core and
      triangulation of WTA phosphate residues with polar contacts. These studies reveal
      the molecular basis for targeting a unique S. aureus cell surface epitope and
      highlight the power of human patient-based antibody discovery techniques for
      finding novel pathogen-targeting therapeutics.

PMID- 30102108
TI  - Electromyographic analysis of hip adductor muscles in soccer instep and side-foot
      kicking.
AB  - A possible link between soccer-specific injuries, such as groin pain and the
      action of hip adductor muscles has been suggested. This study aimed to
      investigate neuromuscular activation of the adductor magnus (AM) and longus (AL)
      muscles during instep and side-foot soccer kicks. Eight university soccer players
      performed the two types of kick at 50%, 75% and 100% of the maximal ball speed.
      Surface electromyography (EMG) was recorded from the AM, AL, vastus lateralis
      (VL) and biceps femoris (BF) muscles of both kicking and supporting legs and the
      kicking motions were three-dimensionally captured. In the kicking leg, an
      increase in surface EMG with an increase in ball speed during instep kicking was
      noted in the AM muscle (p < 0.016), but not in AL, VL or BF muscles (p > 0.016).
      In the supporting leg, surface EMG of both AM and AL muscles was significantly
      increased with an increase in the ball speed before ball impact during both
      instep and side-foot kicks (p < 0.016). These results suggest that hip adductor
      muscles markedly contribute to either the kicking or supporting leg to emphasise
      the action of soccer kicks.

PMID- 30102109
TI  - Parent depressive symptoms and offspring executive functioning.
AB  - INTRODUCTION: Previous research has found mixed results when assessing the
      association between a parent's history of depressive symptoms and a child's
      abilities on measures of executive functioning. The purpose of this study was to
      replicate and expand upon these findings by evaluating the influence of a
      parent's depressive symptoms on a young person's executive functioning. METHOD:
      As part of a larger study, 135 children (54.8% female, aged 8-12) and one
      biological parent completed diagnostic screening interviews. Children then
      completed a brief executive functioning battery. Symptoms endorsed under the past
      major depressive episode module of the MINI International Neuropsychiatric
      Interview was used to measure depressive symptoms of parents. RESULTS: While
      controlling for parent alcohol status and age, gender, intelligence, and current
      depressive symptoms of the child, linear regression models revealed that the
      parent's depressive symptoms significantly predicted deficits in Letter-Number
      Sequencing [b = -0.15 (0.07), p < .05] and Motor Speed [b = -0.17 (0.05), p <
      .005] on the Delis-Kaplan Executive Function System (D-KEFS) Trails Test. Parent
      depressive symptoms had no relationship with inhibition on the D-KEFS Color-Word
      Interference Test [b = -0.04 (0.14), p = .74] or the Verbal Working Memory
      subtest of the Stanford-Binet [b = 0.14 (0.12) p = .43]. Greater depressive
      symptoms in parents were associated with fewer perseverative errors on the
      Wisconsin Card Sorting Task (WCST) [b = 0.73 (0.32), p < .05]. CONCLUSION: In
      sum, a parent's depressive symptomatology was differentially associated with a
      young person's neurocognitive abilities. Clinical implications were discussed.

PMID- 30102110
TI  - First Report of Hibiscus Chlorotic Ringspot Virus Infecting Hibiscus in Fujian
      Province, China.

PMID- 30102111
TI  - Extremely poor patient-reported outcomes are associated with lack of clinical
      response and decreased retention rate of tumour necrosis factor inhibitor
      treatment in patients with axial spondyloarthritis.
AB  - OBJECTIVE: To investigate whether axial spondyloarthritis (axSpA) patients with
      extremely poor patient-reported outcomes (PROs) at start of first tumour necrosis
      factor inhibitor (TNFi) treatment have poorer treatment response and shorter
      treatment retention than other patients. METHOD: This observational cohort study
      was based on the nationwide DANBIO registry. Patients with axSpA who started
      first TNFi during 2011-2016 were stratified according to baseline Bath Ankylosing
      Spondylitis Disease Activity Index (BASDAI >= 0.0 to <= 4.0, > 4.0 to <= 5.0, >
      5.0 to <= 6.0, > 6.0 to <= 7.0, > 7.0 to <= 8.0, > 8.0 to <= 9.0, and > 9.0 to <=
      10.0). An extremely poor BASDAI was defined as BASDAI > 9.0 to <= 10.0. Treatment
      responses after 6 months [>= 50% improvement from baseline BASDAI (BASDAI50), >=
      40% improvement in Assessment of SpondyloArthritis international Society (ASAS40)
      response, and ASAS partial remission] in patients with extremely poor PROs were
      compared with other patients by chi-squared tests, and retention rates by log
      rank tests. Similar analyses were done for Bath Ankylosing Spondylitis Functional
      Index (BASFI), pain score, and patient global score. RESULTS: The study included
      1396 patients (median age 39 years, 60% men). Patients with extremely poor
      baseline BASDAI [63 patients (5%)] were more often women, ever smokers, and human
      leucocyte antigen-B27 negative, and had higher body mass index. Response rates
      were poorer in patients with extremely poor BASDAI vs remaining patients
      (BASDAI50 19% and 41%, respectively, p < 0.001; ASAS40 16% and 35%, p = 0.002;
      ASAS partial remission 6% and 22%, p < 0.001). Patients with extremely poor
      BASDAI had lower 1 year treatment retention (51% and 68%, p < 0.001). Largely
      similar results were found for patients with extremely poor BASFI, pain score,
      and patient global score. CONCLUSION: Patients who reported an unusually large
      symptom burden at baseline had poor response rates and low retention rate. In
      such cases, competing causes of pain should carefully be taken into account when
      considering treatment with TNFi.

PMID- 30102112
TI  - T3 level may be a helpful marker to predict disease prognosis of acute central
      nervous system viral infections.
AB  - AIM OF THE STUDY: Acute central nervous system viral infections are progressive
      and inflammatory diseases with inflammatory cells infiltrating into the central
      nervous system (CNS), and thyroid hormone (TH) level is associated with the
      oxidative and antioxidant status. Variations in oxidative stress and antioxidant
      status are related to the pathogenesis of inflammatory diseases. Our study aimed
      to investigate the possible correlation between viral infections in CNS and TH
      levels of thyroid stimulating hormone (TSH), free thyroxine (fT4) and free
      triiodothyronine (fT3). MATERIALS AND METHODS: We measured serum concentrations
      of TSH, fT4, and fT3 in 206 individuals, including 59 viral meningitis (VM)
      patients, 60 viral encephalitis (VE) patients, and 87 healthy controls. RESULTS:
      Our findings showed that VE and VM patients had lower levels of fT3 and higher
      levels of fT4 compared with healthy controls, whether male or female. Moreover,
      levels of TSH and fT3 in patients with viral infections in CNS were inversely
      correlated with disease prognosis measured by the Glasgow Outcome Scale.
      CONCLUSIONS: Variations in TH level may represent the oxidative status and are
      surrogate biomarkers for disease prognosis of acute central nervous system viral
      infections.

PMID- 30102113
TI  - Demystifying the role of emotion in behaviour: toward a goal-directed account.
AB  - The paper sketches the historical development from emotion as a mysterious entity
      and the source of maladaptive behaviour, to emotion as a collection of
      ingredients and the source of also adaptive behaviour. We argue, however, that
      the underlying mechanism proposed to take care of this adaptive behaviour is not
      entirely up for its task. We outline an alternative view that explains so-called
      emotional behaviour with the same mechanism as non-emotional behaviour, but that
      is at the same time more likely to produce adaptive behaviour. The phenomena that
      were initially seen as requiring a separate emotional mechanism to influence and
      cause behaviour can also be explained by a goal-directed mechanism provided that
      more goals and other complexities inherent in the goal-directed process are taken
      into account.

PMID- 30102114
TI  - Unusual presentation of syncytial variant of nodular sclerosis classical
      Hodgkin's lymphoma presenting as unilateral lung mass in a 15-year-old child.

PMID- 30102116
TI  - Greater naturally occurring expressive suppression is associated with poorer
      executive functioning and motor-sequence learning among older adults.
AB  - OBJECTIVES: Unusually high engagement in expressive suppression (i.e., purposeful
      regulation of overt affect) has been associated with poorer performance on
      executive functioning (EF) and motor-sequence learning tasks. As such, expressive
      suppression represents one possible source of fluctuations in executive test
      performance. However, the relationship between expressive suppression and EF and
      motor performance has not yet been examined in older adults, who are more prone
      to EF and motor fluctuations than are younger adults. The purpose of this study
      was to test whether greater self-reported, naturally occurring expressive
      suppression is related to poorer EF performance and motor-sequence learning in
      older adults. METHOD: One hundred and ten community-dwelling older adults
      completed a self-report measure of expressive suppression, a battery of EF tests,
      and a computer-based measure of motor-sequence learning. RESULTS: As expected,
      higher self-reported burden of expressive suppression in the 24 hours prior to
      testing was related to poorer performance on EF tests and on multiple aspects of
      motor-sequence learning (action planning latencies and sequencing errors) even
      after accounting for age, depressive symptoms, and component processes (e.g.,
      processing speed). CONCLUSIONS: The current results suggest that naturally
      occurring expressive suppression depletes EF, which builds on previous findings
      from experimental studies that show that expressive suppression leads to reduced
      EF performance. Furthermore, this effect can be captured using self-report
      methods. These findings highlight expressive suppression as one source of
      intraindividual fluctuations in executive and motor functioning, which likely
      place older adults at risk for both functional and motor lapses (e.g., medication
      mistakes, falls).

PMID- 30102117
TI  - Using integrated technology to create quality care for older adults: a
      feasibility study.
AB  - PURPOSE: Slow changes in older adults' health status are often not detected until
      they escalate. Our aim was to understand if e-technology can enhance the safety
      and quality of older adult care by detecting changes in health status early.
      METHODS: E-technology was implemented with 30 seniors in an assisted living
      facility. We used wireless devices to monitor blood pressure, oxygen saturation,
      weight, and hydration. This 1-year feasibility study included: a readiness
      assessment, procuring devices, developing an alert software, training staff, and
      weekly monitoring for several months. RESULTS: Analysis of service utilization
      data showed no significant differences in number of emergency or hospital visits
      between the intervention and control group. Qualitative data suggested residents
      were satisfied with the e-technology. Among staff, several saw value in weekly
      monitoring, however staff emphasized the need for devices to be suitable for
      older adults. CONCLUSION: It is imperative that researchers work with facilities
      to ensure there is value-added in implementing new technology. Staff feedback
      helped fine-tune devices, training materials, and measurement process. It took
      longer than anticipated to procure suitable devices, set up the software, and
      recruit residents, thus limiting data collection. Future studies should dedicate
      more time to implementation and propose longer timelines.

PMID- 30102118
TI  - Development of a western blot method for detection of fish ectoparasite Argulus
      siamensis antigens.
AB  - A study was undertaken to develop a western blot method for detection of
      immunogenic proteins of fish ectoparasite, Argulus siamensis for its further use
      as potential vaccine candidates. Argulus antigens were prepared by homogenization
      and injected to rohu (Labeo rohita) juveniles for development of immune serum.
      The serum was used to immunostain the antigens in western blot. The other
      reagents added in sequence were rabbit anti-rohu serum, goat anti-rabbit ALP
      conjugate and substrate (BCIP-NBT). However, similar banding patterns were
      observed with both control and immunized rohu serum. Hence, a possible cross
      reaction was suspected and verified in number of western blot experiments. A
      typical cross-reaction observed was of rabbit serum reacting directly with
      Argulus antigens. Hence, the rabbit anti-rohu serum was replaced with guinea pig
      anti-rohu serum. Another cross-reaction of goat anti-guinea pig ALP conjugate
      with rohu serum was eliminated by using goat anti-rabbit ALP conjugate with
      guinea pig serum. Thus, the final western blot method consisting of Argulus
      antigens -> rohu serum -> guinea pig anti-rohu serum -> goat anti-rabbit ALP
      conjugate -> substrate, yielded distinguishing results between control and
      Argulus-immunized rohu serum samples. The developed test has tremendous
      downstream applications, particularly in immunoproteomic studies of Argulus
      antigens.

PMID- 30102119
TI  - Scaling isometric mid-thigh pull maximum strength in division I Athletes: are we
      meeting the assumptions?
AB  - This study examined the validity of various scaling methods, isometric mid-thigh
      pull (IMTP) peak force using various scaling methods, and the relationships
      between IMTP peak force and countermovement jump height.  Fifty-one collegiate
      baseball and soccer athletes performed two maximal IMTPs.  Absolute peak force
      was compared between teams and when data were scaled using ratio (RS),
      traditional allometric (ALLOTrad), and fitted allometric (ALLOFit) scaling. 
      ALLOTrad and ALLOFit validity was violated because different derived exponents
      existed for baseball (b = 0.20) and soccer (b = 1.20).  Soccer athletes produced
      greater RS peak force compared to baseball (p = 0.012), while no difference
      existed with absolute, ALLOTrad or ALLOFit (all p > 0.05) peak force.  Moderate
      relationships existed between body mass and absolute (r = 0.402, p = 0.003) and
      RS (r = -0.328, p = 0.019) peak force, while trivial relationships existed with
      ALLOTrad and ALLOFit (both r < -0.10, p > 0.05).  Trivial relationships existed
      between countermovement jump height and absolute, RS, ALLOTrad, and ALLOFit (all
      r < 0.20, p > 0.05) peak force.  The current dataset violated allometric scaling
      assumptions, making it inappropriate to use ALLOTrad and ALLOFit scaling. 
      Practitioners must understand the assumptions, limitations, and purpose of
      scaling methods.

PMID- 30102120
TI  - Taurine enhances mouse cochlear neural stem cells proliferation and
      differentiation to sprial gangli through activating sonic hedgehog signaling
      pathway.
AB  - To investigate the molecular mechanism underlying taurine-stimulated
      proliferation and differentiation of cochlear neural stem cells (NSCs) and
      potential involvement of Sonic Hedgehog (Shh) pathway. The NSCs were
      characterized with immunofluorescence stained with nestin antibody. Cell
      viability was determined by MTT assay. The relative proliferation was measured by
      BrdU incorporation assay. The morphologic index was measured under light
      microscope. The relative protein level was determined by immunoblotting. Here we
      presented our findings that taurine stimulated proliferation and neurite
      outgrowth of NSCs, which was completely abolished by Shh inhibitor cyclopamine.
      In addition, cyclopamine antagonized taurine's effect on glutamatergic and
      GABAergic neuron population via suppressing expressions of Ptc-1, Smo and Gli-1.
      Our data supported the critical role of Shh pathway underlying the protective
      effect of taurine on auditory neural system.

PMID- 30102121
TI  - Fixed-bed column system for Cd2+ uptake from aqueous solution by sodium- and
      thiourea-modified clinoptilolite-rich tuff.
AB  - Two kinds of clinoptilolite-rich tuffs from the state of Sonora (Mexico),
      previously treated with NaCl solution and then modified with thiourea, were
      investigated to remove Cd2+ from aqueous solution in a fixed-bed column system.
      Experiments were conducted with a 30 mg L-1 Cd2+ solution at a pH value of 5 and
      three-bed heights of sodium- and thiourea-modified clinoptilolite-rich tuffs. The
      experimental data were examined with the bed depth service time model (BDST), the
      Thomas model, and a mass balance approach. According to the BDST model, the
      dynamic sorption capacity (No) for the thiourea-modified clinoptilolite-rich tuff
      was 0.0357 Kg L-1. This value corresponded to 1.2 times higher than that for
      sodium-modified clinoptilolite-rich tuff (0.0287 Kg L-1). The experimental data
      obtained for sodium- modified clinoptilolite-rich tuff (ZSGNa) with 3 cm of bed
      height, fitted to the Thomas model, with R2 = 0.9679 and Cd sorption capacity of
      35.4 mg g-1, while for the thiourea-modified clinoptilolite-rich tuff (ZSGThio)
      with 4.5 cm of bed height, was 36.52 mg g-1 with R2 = 0.9368. The parameters
      calculated with the mass balance model describe a favourable process where the
      system with ZSGThio (6 cm bed height) had the best performance for sorption
      capacity up to the breakthrough point, qb = 22.35 mg g-1. The zeolite modified
      with thiourea exhibited higher capacity in Cd2+ removal than the one modified
      with NaCl, in the column with 6 cm of bed height. To investigate the mechanisms
      of removal of Cd2+ by the modified zeolites, Na+ was measured to determine the
      milliequivalents of cadmium removed.

PMID- 30102122
TI  - Writing tea's empire.

PMID- 30102123
TI  - Differential expression of CCL18 in moderate/severe and mild persistent allergic
      rhinitis and its correlation with disease parameters.
AB  - BACKGROUND AND AIMS: This study aimed to assess the level of the expression of
      CCL-18 on nasal inferior turbinate mucosa in patients with mild (M) and moderate
      to-severe (M/S) persistent allergic rhinitis (PAR). METHODS: The participants in
      this case-controlled study were divided into three groups: patients with M/S PAR,
      patients with M PAR, and the healthy control group. Biopsies of nasal inferior
      turbinate mucosa were obtained from the participants. Expression of CCL-18 mRNA
      was evaluated by real-time PCR. The serum levels of CCL-18 were determined by
      ELISA. Total serum IgE levels and specific serum IgE levels were measured. The
      clinical manifestations were assessed using the total nasal syndrome score
      (TNSS). RESULTS: Gene expression and the serum level of CCL-18 in patients with
      M/S PAR increased significantly compared to the control group and patients with M
      PAR. The serum level of CCL-18 was found to correlate with TNSS in patients with
      M/S PAR. There was a statistical correlation between the serum level of CCL-18
      and the total serum IgE in the treatment groups. CONCLUSION: The results of the
      study indicate that there could be a relationship between the expression of CCL
      18 in nasal turbinate mucosa and the severity of allergic rhinitis.

PMID- 30102124
TI  - Exposure to gangs in low-income urban communities and substance use among
      Hispanic youth.
AB  - A third of Hispanic youth live below the poverty line, making them vulnerable for
      exposure to gangs, substances, and violence, all of which have been associated
      with substance use. The aim of the present study was to test the link between
      these variables, using a multiple mediation model. Results suggest that the
      relationship between gang exposure and adolescent substance use was mediated by
      both access to substances and exposure to violence. Findings provide insight into
      how gang exposure impacts outcomes for low-income youth. Implications for
      prevention and policy are discussed.

PMID- 30102125
TI  - Dynamics of child marriage and marital timing in Nigeria: A retrogression or
      progression?
AB  - The researcher assessed trends and patterns of marital timing and child marriage
      (CM) among women of reproductive age in Nigeria. Four rounds of Nigeria
      Demographic and Health Survey data-set were used (1990-2013). Data were analyzed
      using descriptive statistics and Cox-regression model with time-dependent
      covariates (alpha = 0.05). CM (<18 years) falls consistently from 63.8% in 1990
      to 56.3% in 2013. The hazard ratio of CM was 1.24 (CI =1.19-1.28, p < .001), 1.24
      (CI =1.19-1.29, p < .001), and 1.05 (CI =1.02-1.07, p < .001) times higher in
      1990, 2003, and 2008, respectively than 2013. The region, education, religion,
      and ethnicity are common predictors of CM in all the survey rounds.

PMID- 30102126
TI  - Use of hybrid microcapsules, chitosan-methyl esterified sericite-tannin, for the
      removal of harmful lake algae and nutrient.
AB  - This paper outlines the development of a novel, low-cost, hybrid material from
      chitosan-methyl esterified sericite-tannin. The adsorbent material is then
      successfully utilized for the efficient removal of lake nutrients and harmful
      algae. In a FT-IR analysis, peaks related to -OH stretching, carbonyl and
      carboxylic groups, and CH stretching were newly created or expanded, and
      microcapsules were found to facilitate the removal of harmful algae and
      nutrients. The hybrid microcapsules obtained high removal efficiencies of 98% TN,
      98% TP, and 99% Chl-a from the lake water by a quantity of hybrid microcapsules
      of 1 g/L, pH (7-8), and 30 min contact time at (25-30) degrees C. In addition,
      the experimental data were applied to various harmful algae growth models and
      were most suitable for the Heldane model. Based on the above results,
      microcapsules can be applied in the field, and can be expected to rapidly remove
      nutrients and harmful algae.

PMID- 30102127
TI  - Treated residue from aluminium lamination as adsorbent of toxic reactive dyes - a
      kinetic, equilibrium and thermodynamic study.
AB  - The residue generated in the aluminium cold lamination (TTR) was submitted to a
      direct burning and then it was calcined at 500 degrees C. BET, FTIR, SEM with EDX
      and TGA techniques were performed to characterize the adsorbent before and after
      the adsorption. BET analysis showed that TTR specific surface area was 55.37 m2 g
      1 and there were no significant changes after the adsorptive process. Afterwards,
      the TTR was applied as adsorbent of the reactive Drimaren Blue (DB), Drimaren Red
      (DR) and Drimaren Gold (DG). Its employment consists in a sustainable alternative
      for the treatment of textile wastewater, once the TTR was used as low-cost
      adsorbent of textile dyes. Kinetic studies showed that the process reached the
      equilibrium state between 5 and 10 min. The pseudo-second-order model better
      fitted the adsorption kinetics, with kinetic rate constants 10.51, 34.71 and
      31.51 mg min g-1 for DB, DR and DG respectively. The equilibrium experiments were
      performed to obtain the adsorption parameters for each dye; moreover, the maximum
      adsorption capacity was 6.27, 0.42 and 1.23 mg g-1 for DB, DR and DG,
      respectively. Thermodynamics studies allowed to obtain the values of enthalpy for
      DB, DR and DG, -7.90, 14.03 and -17.75 kJ mol-1, respectively. Furthermore, the
      negative values of Gibbs free energy confirmed the spontaneity of the adsorption.
      The results point to the physisorption characteristic of the process, in which
      the temperature negatively influenced the adsorption for the DB and DG; the
      opposite result was observed for the DR.

PMID- 30102128
TI  - Healthcare Chaplaincy as a Companion Profession: Historical Developments.
AB  - Chaplains, like professionals in a range of industries, have long sought to
      maintain and build occupational power by articulating their professional mandate
      and advocating for their work. I describe how leaders of the Association of
      Professional Chaplains and its predecessor organizations used multiple strategies
      to articulate and re-articulate their professional mandate between 1940 and the
      present to become a companion profession, one that comes alongside another
      without seeking to challenge its jurisdiction. I find chaplains seeking to
      develop an economic base, aligning interests across distinct segments of the
      profession and creating new professional associations, lobbying for legislative
      support, and offering their services in institutional voids. They further adopted
      the language of healthcare around questions of identity, charting, and
      accreditation and, chaplains used not just the frameworks but the methods of
      healthcare-evidence based research-to try to demonstrate their value. This
      history can help chaplains and chaplaincy leaders today to form a more
      comprehensive sense of their history and think more strategically regarding how
      to make the case for their profession going forward.

PMID- 30102129
TI  - Preparedness of representatives for people with dementia in a self-directed
      program.
AB  - Representatives enact their role as decision-making partners across the
      intersection of participant direction (PD) and dementia care. Self-rated
      preparedness for key dimensions of the role endorsed by a panel of experts in PD
      and dementia was assessed by telephone survey of 30 representatives of persons
      with dementia in a PD program. The sample (daughters 60%; Black 50%; rural 70%)
      was diverse in length of time in the role and additional responsibilities. They
      represented participants with moderate to advanced dementia and >= two additional
      chronic illnesses. Overall preparedness scores were in the pretty well to very
      well prepared range, with variation across dimensions and between individuals.
      Preparedness varied according to what has to be done day-to-day in dynamic or
      unpredictable situations, gauging decisional capacity, anticipating changing
      needs, ensuring safety, supporting a dementia-capable care team and negotiation.
      Stress was related to having a safety net of capable back-up supports and
      dementia care literacy. Areas of strength, individual variation and particular
      challenges along the trajectory of representing can guide development of support
      counselor interventions to provide representatives with tailored training and
      resources as they enable the benefits of PD for persons with dementia.

PMID- 30102130
TI  - Affective Responses to Gay Men Using Facial Electromyography: Is There a
      Psychophysiological "Look" of Anti-Gay Bias.
AB  - Despite a wealth of attitudinal studies that elucidate the psychological
      correlates of anti-gay bias, studies that provide evidence of the physiological
      correlates of anti-gay bias remain relatively scarce. The present study addresses
      the under-representation of physiological research in the area of homonegativity
      by examining psychophysiological markers, namely the affective manifestations of
      anti-gay prejudice, and their correspondence with anti-gay behavior. Facial
      electromyography (EMG) was the technique used to acquire the psychophysiological
      markers via recordings from two facial muscle sites. Whether heterosexual men's
      implicit affective reactions to gay male couples best predicted their overt and
      covert discriminatory behavior toward a presumed gay male confederate was
      determined. The strength of the implicit affective reactions to predict anti-gay
      discrimination was then tested against the strength of participants' implicit
      cognitive reactions acquired via the Implicit Association Test (IAT). Results
      indicated that the affective reactions recorded via facial EMG emerged as the
      strongest predictor of discrimination toward gay men compared to the cognitive
      reactions recorded using the IAT. Findings support the contention that emotional
      reactions to gay men using implicit techniques such as facial EMG are potentially
      valuable pathways toward understanding the nature and sequelae of anti-gay
      behavior.

PMID- 30102131
TI  - Antibacterial action of functional silicon dioxide: an investigation of the
      attachment and separation of bacteria.
AB  - Bactericidal proteins from the Moringa oleifera seed are reported to be suitable
      alternatives to conventional methods of bacterial reduction in water. In this
      study the cationic bactericidal M. oleifera proteins were isolated by attachment
      onto the surface of silicon dioxide. This functionalised SiO2(f-SiO2) was then
      exposed to Escherichia coli and Micrococcus luteus to examine whether the f-SiO2
      could be used to inactivate the bacteria. The effect of the non-ionic surfactant
      dodecyl glucoside on the attachment of these bacteria to the f-SiO2 was examined
      with the aim of developing a method of reusable bacterial inactivation. The
      primary result of this study was that the E. coli could be readily separated from
      the f-SiO2, allowing the f-SiO2 to be used for further bacterial inactivation.
      The regeneration of the f-SiO2 was demonstrated using fluorescence microscopy on
      bacterial cells stained with propidium iodide, and zeta potential measurements.
      Future applications of this work include a reusable method of removing bacteria
      from contaminated water.

PMID- 30102132
TI  - Identifying disrespect and abuse in organisational culture: a study of two
      hospitals in Mumbai, India.
AB  - This paper draws on findings from a qualitative study of two government hospitals
      in Mumbai, India, which aimed to provide a better understanding of the
      institutional drivers of disrespect and abuse (D&A) in childbirth. The paper
      describes the structural context, in which government hospital providers can
      exercise considerable power over patients, yet may be themselves vulnerable to
      violence and external influence. Decisions that affect care are made by a
      bureaucracy, which does not perceive problems with the same intensity as
      providers who are directly attending to patients. Within this context, while
      contrasting organisational cultures had evolved at the two hospitals, both were
      characterised by social/professional inequality and hierarchical functioning, and
      marginalising women. This context generates invisible pressures on subordinate
      staff, and creates interpersonal conflicts and ambiguity in the division of roles
      and responsibilities that manifest in individual actions of D&A. Services are
      organised around the internal logic of the institution, rather than being centred
      on women. This results in conditions that violate women's privacy, and disregards
      their choice and consent. The structural environment of resource constraints,
      poor management and bureaucratic decision-making leads to precarious situations,
      endangering women's safety. With the institution's functioning based on
      hierarchies and authority, rather than adherence to universal standards or
      established protocols, irrational, harmful practices endorsed by senior staff are
      institutionalised and reproduced. A deeper focus on organisational culture,
      embedded in the discourse of D&A, would help to evolve effective strategies to
      address D&A as systemic problems.

PMID- 30102133
TI  - Heavy metals in seafood purchased from a fishery market in Hungary.
AB  - Heavy-metal content (arsenic, cadmium, lead and mercury) was investigated and
      evaluated in shellfish, oysters and squids. The samples were collected weekly for
      20 weeks from a fishery product market in Hungary. The concentration of heavy
      metals was measured by Inductively Coupled Plasma Optical Emission Spectrometer
      (ICP-OES) analysis after sample preparation. The results were analysed
      statistically by one-way ANOVA method. The average concentration of arsenic (3.01
      +/- 1.46 mg kg-1) in shellfish was significantly higher (p < 0.001) compared to
      oysters (2.88 +/- 1.12 mg kg-1) and squids (1.28 +/- 0.52 mg kg-1). The level of
      mercury was below the limit of detection (0.5 mg kg-1) in each sample and there
      was no statistical significance in the concentrations of cadmium (p = 0.351) and
      lead (p = 0.412) in the species investigated. The provisional tolerable intake
      values were also calculated. Based on the obtained results of the heavy-metal
      content of the investigated samples, the seafood is considered to be safe for
      human consumption. However, prolonged ingestion of oysters and squids at these
      levels may contribute to the consumers' cadmium burden.

PMID- 30102134
TI  - Mentor Mothers Zithulele: exploring the role of a peer mentorship program in
      rural PMTCT care in Zithulele, Eastern Cape, South Africa.
AB  - BACKGROUND: The majority of global HIV infections in children under 10 years of
      age occur during pregnancy, delivery or breastfeeding, despite improved coverage
      of 'prevention of mother-to-child transmission' (PMTCT) guidelines to reduce
      vertical transmission. This article looks closer at one community-based peer
      mentorship programme [Mentor Mothers Zithulele (MMZ)] in the Eastern Cape, South
      Africa which aims to supplement the existing heavily burdened antenatal
      programmes and improve PMTCT care. METHODS: Semi-structured interviews were
      undertaken with HIV-positive women participating in MMZ and women receiving
      standard PMTCT care without any intervention. A focus group discussion (FGD) was
      conducted with women working as Mentor mothers (MMs) for MMZ to explore their
      experience of the impact of peer mentoring on the rural communities they serve.
      RESULTS: Six main themes were identified in the interviews with antenatal
      patients: (i) MMs were a key educational resource, (ii) MMs were important in
      promoting exclusive breastfeeding, (iii) encouraging early HIV testing during
      pregnancy and (iv) providing psychosocial support to patients in their homes,
      thereby reducing stigma and sense of alienation. Respondents requested (v)
      additional focus on HIV education. MMs can (vi) function as a link between
      patients and health-care providers, improving treatment adherence. During the FGD
      two themes emerged; MMs fill the gap between patients and health services, and
      MMZ should focus on HIV awareness and stigma reduction. CONCLUSION: Peer
      mentoring programmes can play an important role in reducing vertical HIV
      transmission in resource-limited, rural settings by providing participants with
      education, psychosocial support, and a continuum of care.

PMID- 30102135
TI  - Fear, Defensive Strategies and Caring for Cognitively Impaired Family Members.
AB  - One topic rarely addressed in the literature on older adults and interpersonal
      violence is the violence that can be experienced by family carers in relationship
      with a person living with cognitive impairment. This violence tends to remain
      hidden and is rarely framed as intimate partner violence. We examine how
      situations of intimidation and violence invoked fear in family carers and how
      they interpreted and reacted to these circum- stances. Interview and diary data
      were collected from family members who had previously or were currently
      experiencing some form of aggression in caring for someone with cognitive
      impairment or dementia. Drawing on discussions of fear and applying the analytic
      lens of defensive strategies, we explore how these carers responded to situations
      of intimidation and violence.

PMID- 30102136
TI  - Kinetic function of the lower limbs during baseball tee-batting motion at
      different hitting-point heights.
AB  - The aim of this study was to investigate the kinetic functions of the lower limbs
      at different hitting-point heights to provide key information for improving
      batting technique in baseball players. Three-dimensional coordinate data were
      acquired using a motion capture system (250 Hz) and ground reaction forces were
      measured using three force platforms (1000 Hz) in 22 male collegiate baseball
      players during tee-batting set at three different hitting-point heights (high,
      middle, and low). Kinetic data were used to calculate joint torque and mechanical
      work in the lower limbs by the inverse dynamics approach. The peak angular
      velocity of the lower trunk about the vertical axis was smaller under the low
      condition. The joint torques and mechanical works done by both hip
      adduction/abduction axes were different among the three conditions. These results
      indicate that hip adduction/abduction torques mainly contribute to a change in
      the rotational movement of the lower body about the vertical axis when adjusting
      for different hitting-point heights. In order to adjust for the low hitting-point
      height which would be difficult compared with other hitting-point heights,
      batters should focus on rotating the lower trunk slowly by increasing both hip
      abduction torques.

PMID- 30102137
TI  - Using morphological, behavioral, and molecular biomarkers in Zebrafish to assess
      the toxicity of lead-contaminated sediments from a retired trapshooting range
      within an urban wetland.
AB  - The widespread use of lead (Pb) shot in shooting activities, including at former
      shooting ranges, continues to pose environmental risks. The La Crosse River Marsh
      (located in Wisconsin, USA) is a biologically diverse urban riparian wetland with
      a legacy of Pb-contaminated sediment resulting from its use as a trap shooting
      range from 1929-1963. Within the shot fall zone, shot densities exceed 43,000
      pellets/m2 and surface sediments exceed 25,000 mg/kg in some areas. This study
      used the Zebrafish as a model to determine the acute toxicity of these
      contaminated sediments. Zebrafish were exposed to sediments containing
      approximately 13 to 13,450 mg/kg Pb for 5 days (8-120 hr post-fertilization). The
      toxic responses to sediments were non-monotonic. Only exposure to sediments
      containing "mid-range" concentrations of Pb (4580 mg/kg) induced mild skeletal
      malformations and a sluggish C-start response indicating that Pb was marginally
      bioavailable. Expression of delta-aminolevulinic acid dehydratase (ALA-D) also
      indicated the potential for uptake of Pb from sediments. Our findings suggest
      that Pb within the La Crosse River Marsh sediments is not readily bioavailable to
      Zebrafish, and while this metal poses a minimal acute toxicological risk,
      toxicity due to chronic exposure of low concentrations of Pb is possible.
      Further, our data demonstrated that induction of ALA-D gene expression in
      Zebrafish embryos shows promise as an alternative to ALA-D enzyme activity as a
      biomarker for acute Pb exposure under lab conditions.

PMID- 30102138
TI  - "Engaging in my rural community": perceptions of people aged 85 years and over.
AB  - PURPOSE:  Globally, numbers of people aged 85 years and over are increasing. Many
      older people, including those 85 years and over, are ageing in rural areas. For
      successful ageing in place, physical and social environments must be appropriate.
      The aim of this study is to understand the influence the physical and social
      environments have on enabling those aged 85 years and over to remain engaged in a
      rural community. Method: Utilizing an environmental gerontological approach, semi
      structured interviews were undertaken with 15 people who lived independently in a
      rural community. Following transcription data were analyzed and themes
      identified. Results: Two themes were identified; "Negotiating the physical
      environment: 'Getting there and back'" and "Maintaining social networks: 'Places
      to go, people to see'". The findings provide insight into the importance of
      driving, parking close to amenities and negotiating the local environment to this
      group of older people and their ability to engage with their community. All
      participants agreed social engagement with friends, family or neighbors was
      important to them. Conclusion: These findings highlight the interconnection
      between physical and social environments. An enabling physical environment is
      essential to support social participation of people aged 85 years and over.

PMID- 30102140
TI  - Ageing well in a foreign land as a process of successful social identity change.
AB  - PURPOSE: Over and above the risks associated with ageing, older migrants are also
      at risk of social isolation. The social identity approach, and the Social
      Identity Model of Identity Change (SIMIC) in particular, provides a theoretical
      basis from which to understand the factors contributing to social isolation and
      how this then impacts on older migrants' capacity to age well in a foreign land.
      Building on the recognition that migration involves a major life change, we
      explore this transition qualitatively focusing specifically on social
      connectedness and adjustment. METHODS: In semi-structured interviews with 29
      older migrants in Australia, we examined participants' experiences of migration
      and perceptions of identity and identity change. We also considered in more
      detail experiences of the most and least socially isolated individuals to
      understand adjustment trajectories. RESULTS: We found evidence supporting the key
      processes described in SIMIC (relating to social identity continuity, social
      identity gain, and perceived identity compatibility), suggesting that where
      adjustment was positive it was experienced as a process of successfully adapting
      to identity change. CONCLUSION: We emphasise the importance of identity resources
      as substantial and concrete assets that can enhance the well-being among older
      adults aging in a foreign land.

PMID- 30102141
TI  - "Fear Runs Deep:" The Anticipated Needs of LGBT Older Adults in Long-Term Care.
AB  - OBJECTIVES: Older lesbian, gay, bisexual, and transgender (LGBT) adults are a
      vulnerable yet resilient population who face unique stressors as they foresee
      health decline. This paper presents the results of a study about community
      dwelling LGBT older adults' anticipated needs and fears related to nursing homes
      and assisted living. METHODS: This qualitative study collected data through seven
      focus groups. The sample (N = 50) consisted of LGBT-identified adults age 55 and
      over. We used an inductive, thematic analysis approach to data analysis. RESULTS:
      Participants seek an inclusive environment where they will be safe and feel
      connected to a community. They fear dependence on healthcare providers, dementia,
      mistreatment, and isolation. Importantly, these fears can lead to identity
      concealment and psychological distress, including suicide ideation. DISCUSSION:
      This study adds to the existing literature about the worries of older LGBT adults
      as they anticipate long-term care. The results suggest that older LGBT adults
      seek LGBT-inclusive residential care settings that encompass two distinct yet
      related aspects of LGBT-affirmative care: the procedural (e.g. culturally
      competent skills and knowledge of practitioners) and the implicit (e.g. the
      values and mission of the organization). This paper identifies implications for
      practice, policy, and training.

PMID- 30102142
TI  - Doctoral students' well-being: a literature review.
AB  - PURPOSE: Doctoral student well-being is an important matter that shapes the well
      being of academics throughout their careers. Given that well-being has been found
      to be closely related to employee productivity and efficiency, strategies
      associated with maintaining well-being during PhD studies might be crucial for
      higher education, its outcomes and-just as importantly-for a balanced life of PhD
      students.  Method: Based on 17 studies, this literature review critically
      assesses the literature on doctoral student well-being.  Results: Theoretical
      models, concepts of well-being, and methods applied are discussed, as are the
      results of the articles. The reviewed studies are then discussed based on a SWOT
      analysis addressing the strengths and weaknesses of the reviewed research as well
      as the identified opportunities and threats, which can be used as a basis for
      future research. Based on the review findings and the SWOT analysis, a
      multidimensional view of the well-being of doctoral students is proposed. 
      Conclusions: The study proposes a more student-centred approach to meeting
      doctoral students' needs, and the enhancement of doctoral student well-being in
      order, as a long-term goal, to improve academics' well-being and
      productivity.Doctoral student well-being is an important matter that shapes the
      well-being of academics throughout their careers. Given that well-being has been
      found to be closely related to employee productivity and efficiency, strategies
      associated with maintaining well-being during PhD studies might be crucial for
      higher education, its outcomes and-just as importantly-for a balanced life of PhD
      students. Based on 17 studies, this literature review critically assesses the
      literature on doctoral student well-being. Theoretical models, concepts of well
      being, and methods applied are discussed, as are the results of the articles. The
      reviewed studies are then discussed based on a SWOT analysis addressing the
      strengths and weaknesses of the reviewed research as well as the identified
      opportunities and threats, which can be used as a basis for future research.
      Based on the review findings and the SWOT analysis, a multidimensional view of
      the well-being of doctoral students is proposed. The study proposes a more
      student-centred approach to meeting doctoral students' needs, and the enhancement
      of doctoral student well-being in order, as a long-term goal, to improve
      academics' well-being and productivity.

PMID- 30102143
TI  - Streptacidiphilus pinicola sp. nov., isolated from pine grove soil.
AB  - A moderately acidophilic actinobacterial strain, designated MMS16-CNU450T, was
      isolated from pine grove soil, and its taxonomic position was analysed using a
      polyphasic approach. The isolate showed best growth at 30  degrees C, pH 6 and
      0.5 % (w/v) NaCl. On the basis of 16S rRNA gene sequence similarity, the isolate
      was assigned to the genus Streptacidiphilus, and the closest species were
      Streptacidiphilus rugosus AM-16T (sequence similarity, 98.61 %),
      Streptacidiphilus melanogenes NBRC 103184T (98.53 %), Streptacidiphilus
      jiangxiensis NBRC 100920T (98.19 %) and Streptacidiphilus anmyonensis NBRC
      103185T (98.05 %). The isolate formed a distinct cluster of its own within the
      Streptacidiphilusclade in the phylogenetic tree. Based on whole-genome comparison
      between the strain MMS16-CNU450T and the type strains of related species, the
      orthologous average nucleotide identity and in silico DNA-DNA hybridization
      values were in the range of 77.9-87.0 and 22.3-32.7 %, respectively. The DNA G+C
      content of the isolate was 68.6 mol%. The phylogenetic, phenotypic,
      chemotaxonomic and genomic data supported the affiliation of the strain to
      Streptacidiphilus, and the name Streptacidiphilus pinicola sp. nov. (type strain,
      MMS16-CNU450T=KCTC 49008T=JCM 32300T) is proposed accordingly.

PMID- 30102144
TI  - Evaluation of anticoagulant agents for the treatment of human metapneumovirus
      infection in mice.
AB  - Thrombin has been demonstrated to be involved in several viral diseases including
      human metapneumovirus (hMPV) infections. We previously showed that immediate
      administration of thrombin inhibitor argatroban post-infection protected mice
      against hMPV disease. This current work aims at determining whether warfarin and
      heparin, two other anticoagulants inhibiting thrombin formation and activities,
      may also be used for treatment against hMPV in vivo. We found that immediate
      injections of argatroban, warfarin or heparin after virus challenge protected
      mice against hMPV infection, as evidenced by decreased or no mortality, less
      weight loss, reduced viral load and attenuated inflammation. However, delayed
      treatments starting 1 day post-infection with argatroban or warfarin almost did
      not impact the survival whereas delayed treatment with heparin induced an
      increased mortality during infection. Moreover, these treatments also did not
      reduce weight loss, viral replication and inflammation. In agreement with these
      results, thrombin generation was decreased upon immediate anticoagulant
      treatments but was unaltered upon delayed treatments. Thus, thrombin generation
      occurs at the onset of hMPV infection and thrombin inhibition may be only useful
      for the treatment of this disease when initiated in the early stage. In this
      case, heparin is not recommended because of its reduced efficacy on mortality in
      infected mice whereas argatroban and warfarin appear as safe and effective drugs
      for the treatment of hMPV disease. The antiviral and anti-inflammatory effects of
      argatroban occur via thrombin-dependent pathways whereas the mechanisms by which
      warfarin exerts its beneficial effects against hMPV infection were not elucidated
      and need to be further studied.

PMID- 30102145
TI  - Isolation and characterization of a novel phage Xoo-sp2 that infects Xanthomonas
      oryzae pv. oryzae.
AB  - Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is a
      serious bacterial disease in rice-growing regions worldwide. Phage therapy has
      been proposed as a potential measure to treat bacterial infections. In this
      study, a novel phage, Xoo-sp2, which infects Xoo was isolated from soil. The
      characteristics of Xoo-sp2, including the morphology, one-step growth curve and
      host range, were analysed. The genome of phage Xoo-sp2 was sequenced and
      annotated. The results demonstrated that Xoo-sp2 is a siphovirus and has a broad
      lytic spectrum, infecting 9 out of 10 representative Xoo strains. Genome analysis
      showed that the Xoo-sp2 genome consists of a linear double-stranded DNA molecule
      of length 60 370 bp. Annotation of the whole genome indicated that Xoo-sp2
      encodes 79 putative open reading frames (ORFs). Comparative genomics analysis of
      Xoo-sp2 showed that it shares significant similarity only with Pseudomonas and
      Stenotrophomonas phages (with maximum identity reaching 80 % along 69 % of the
      genome), and thus represents a novel Xanthomonas phage. Xoo-sp2 significantly
      inhibited Xoo growth in liquid culture. An experiment with potted plants
      indicated that Xoo-sp2 could efficiently control BLB in living rice. In summary,
      our work characterized a novel Xanthomonas phage and demonstrated its potential
      as a prophylactic agent in the control of BLB in rice.

PMID- 30102146
TI  - Ottowia oryzae sp. nov., isolated from Andong sikhye, a Korean traditional rice
      beverage.
AB  - A Gram-stain-negative, non-spore-forming, non-motile, short-rod-shaped bacterial
      strain, designated KADR8-3T, isolated from Andong sikhye in Andong-si,
      Gyeongsangbuk-do, Republic of Korea, was characterized using a polyphasic
      approach. On the basis of morphological, genetic and chemotaxonomic
      characteristics, it was determined to belong to the genus Ottowia. The
      phylogenetic similarity based on the 16S rRNA gene sequences indicated the strain
      formed a clade with Ottowia beijingensis GCS-AN-3T, Ottowia thiooxydans DSM
      14619T, Ottowia pentelensis RB3-7T and 'Ottowia shaoguanensis' J5-66T, showing
      the highest similarity to O. beijingensis GCS-AN-3T (96.3 %). The major fatty
      acids were C16 : 0, summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c) and
      summed feature 8 (C18 : 1omega6c and/or C18 : 1omega7c). The predominant
      respiratory quinone was Q-8. The polar lipids present were
      diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylmonomethylethanolamine, two unidentified aminolipids and two
      unidentified lipids. The genomic DNA G+C content was 66.80 mol%. These results
      supported that strain KADR8-3T was clearly distinguishable from its closely
      related species and represents a novel species of the genus Ottowia, for which
      the name Ottowia oryzae is proposed. The type strain is KADR8-3T (=KACC
      19325T=NBRC 113109T).

PMID- 30102147
TI  - Genetics of biosynthesis and structure of the K53 capsular polysaccharide of
      Acinetobacter baumannii D23 made up of a disaccharide K unit.
AB  - The KL53 capsular polysaccharide (CPS) gene cluster of Acinetobacter baumannii
      D23 was sequenced, and includes a single gtr gene encoding the
      glycosyltransferase Gtr2, and the itrA1 gene for ItrA1 that is known to initiate
      CPS biosynthesis with d-QuiNAc4NAc. The K53 CPS was isolated and studied by one-
      and two-dimensional 1H and 13C nuclear magnetic resonance (NMR) spectroscopy
      before and after O-deacetylation. The disaccharide K unit of the CPS was
      established as ->3)-alpha-d-GalpNAcA4Ac-(1->3)-beta-d-QuipNAc4NAc-(1->, where
      GalNAcA and QuiNAc4NAc indicate 2-acetamido-2-deoxygalacturonic acid and 2,4
      diacetamido-2,4,6-trideoxyglucose, respectively. This established the linkage
      formed by Gtr2. The degree of 4-O-acetylation of d-GalNAcA by Atr18, encoded at
      the KL53 locus, is ~55 %.

PMID- 30102148
TI  - Human glucose-regulated protein 78 modulates intracellular production and
      secretion of nonstructural protein 1 of dengue virus.
AB  - Virus-host interactions play important roles in virus infection and host cellular
      response. Several viruses, including dengue virus (DENV), usurp host chaperones
      to support their amplification and survival in the host cell. We investigated the
      interaction of nonstructural protein 1 (NS1) of DENV with three endoplasmic
      reticulum-resident chaperones (i.e. GRP78, calnexin and calreticulin) to
      delineate their functional roles and potential binding sites for protein complex
      formation. GRP78 protein showed prominent association with DENV NS1 in virus
      infected Huh7 cells as evidenced by co-localization and co-immunoprecipitation
      assays. Further studies on the functional interaction of GRP78 protein were
      performed by using siRNA-mediated gene knockdown in a DENV replicon transfection
      system. GRP78 knockdown significantly decreased intracellular NS1 production and
      delayed NS1 secretion but had no effect on viral RNA replication. Dissecting the
      important domain of GRP78 required for DENV NS1 interaction showed co
      immunoprecipitation of DENV NS1 with a full-length and substrate-binding domain
      (SBD), but not an ATPase domain, of GRP78, confirming their interaction through
      SBD binding. Molecular dynamics simulations of DENV NS1 and human GRP78 complex
      revealed their potential binding sites through hydrogen and hydrophobic bonding.
      The majority of GRP78-binding sites were located in a beta-roll domain and
      connector subdomains on the DENV NS1 structure involved in hydrophobic surface
      formation. Taken together, our findings demonstrated the roles of human GRP78 in
      facilitating the intracellular production and secretion of DENV NS1 as well as
      predicted potential binding sites between the DENV NS1 and GRP78 complex, which
      could have implications in the future development of target-based antiviral
      drugs.

PMID- 30102149
TI  - Extinction recall of fear memories formed before stress is not affected despite
      higher theta activity in the amygdala.
AB  - Stress is known to exert its detrimental effects not only by enhancing fear, but
      also by impairing its extinction. However, in earlier studies stress exposure
      preceded both processes. Thus, compared to unstressed animals, stressed animals
      had to extinguish fear memories that were strengthened by prior exposure to
      stress. Here, we dissociate the two processes to examine if stress specifically
      impairs the acquisition and recall of fear extinction. Strikingly, when fear
      memories were formed before stress exposure, thereby allowing animals to initiate
      extinction from comparable levels of fear, recall of fear extinction was
      unaffected. Despite this, we observed a persistent increase in theta activity in
      the BLA. Theta activity in the mPFC, by contrast, was normal. Stress also
      disrupted mPFC-BLA theta-frequency synchrony and directional coupling. Thus, in
      the absence of the fear-enhancing effects of stress, the expression of fear
      during and after extinction reflects normal regulation of theta activity in the
      mPFC, not theta hyperactivity in the amygdala.

PMID- 30102150
TI  - Prolonged cross-bridge binding triggers muscle dysfunction in a Drosophila model
      of myosin-based hypertrophic cardiomyopathy.
AB  - K146N is a dominant mutation in human beta-cardiac myosin heavy chain, which
      causes hypertrophic cardiomyopathy. We examined how Drosophila muscle responds to
      this mutation and integratively analyzed the biochemical, physiological and
      mechanical foundations of the disease. ATPase assays, actin motility, and
      indirect flight muscle mechanics suggest at least two rate constants of the cross
      bridge cycle are altered by the mutation: increased myosin attachment to actin
      and decreased detachment, yielding prolonged binding. This increases isometric
      force generation, but also resistive force and work absorption during cyclical
      contractions, resulting in decreased work, power output, flight ability and
      degeneration of flight muscle sarcomere morphology. Consistent with prolonged
      cross-bridge binding serving as the mechanistic basis of the disease and with
      human phenotypes, 146N/+ hearts are hypercontractile with increased tension
      generation periods, decreased diastolic/systolic diameters and myofibrillar
      disarray. This suggests that screening mutated Drosophila hearts could rapidly
      identify hypertrophic cardiomyopathy alleles and treatments.

PMID- 30102154
TI  - Dark clouds over Indonesia.

PMID- 30102151
TI  - Cerebellar involvement in an evidence-accumulation decision-making task.
AB  - To make successful evidence-based decisions, the brain must rapidly and
      accurately transform sensory inputs into specific goal-directed behaviors. Most
      experimental work on this subject has focused on forebrain mechanisms. Using a
      novel evidence-accumulation task for mice, we performed recording and
      perturbation studies of crus I of the lateral posterior cerebellum, which
      communicates bidirectionally with numerous forebrain regions. Cerebellar
      inactivation led to a reduction in the fraction of correct trials. Using two
      photon fluorescence imaging of calcium, we found that Purkinje cell somatic
      activity contained choice/evidence-related information. Decision errors were
      represented by dendritic calcium spikes, which in other contexts are known to
      drive cerebellar plasticity. We propose that cerebellar circuitry may contribute
      to computations that support accurate performance in this perceptual decision
      making task.

PMID- 30102155
TI  - Corrections.

PMID- 30102156
TI  - LoveYourself: a safe environment for testing and treatment.

PMID- 30102153
TI  - CCR7 defines a precursor for murine iNKT cells in thymus and periphery.
AB  - The precise steps of iNKT subset differentiation in the thymus and periphery have
      been controversial. We demonstrate here that the small proportion of thymic iNKT
      and mucosal associated invariant T cells that express CCR7 represent a multi
      potent progenitor pool that gives rise to effector subsets within the thymus.
      Using intra-thymic labeling, we also showed that CCR7+ iNKT cells emigrate from
      the thymus in a Klf2 dependent manner, and undergo further maturation after
      reaching the periphery. Ccr7 deficiency impaired differentiation of iNKT effector
      subsets and localization to the medulla. Parabiosis and intra-thymic transfer
      showed that thymic NKT1 and NKT17 were resident-they were not derived from and
      did not contribute to the peripheral pool. Finally, each thymic iNKT effector
      subset produces distinct factors that influence T cell development. Our findings
      demonstrate how the thymus is both a source of iNKT progenitors and a unique site
      of tissue dependent effector cell differentiation.

PMID- 30102152
TI  - Autophagy-dependent ribosomal RNA degradation is essential for maintaining
      nucleotide homeostasis during C. elegans development.
AB  - Ribosome degradation through the autophagy-lysosome pathway is crucial for cell
      survival during nutrient starvation, but whether it occurs under normal growth
      conditions and contributes to animal physiology remains unaddressed. In this
      study, we identified RNST-2, a C. elegans T2 family endoribonuclease, as the key
      enzyme that degrades ribosomal RNA in lysosomes. We found that loss of rnst-2
      causes accumulation of rRNA and ribosomal proteins in enlarged lysosomes and both
      phenotypes are suppressed by blocking autophagy, which indicates that RNST-2
      mediates autophagic degradation of ribosomal RNA in lysosomes. rnst-2(lf) mutants
      are defective in embryonic and larval development and are short-lived.
      Remarkably, simultaneous loss of RNST-2 and de novo synthesis of pyrimidine
      nucleotides leads to complete embryonic lethality, which is suppressed by
      supplements of uridine or cytidine. Our study reveals an essential role of
      autophagy-dependent degradation of ribosomal RNA in maintaining nucleotide
      homeostasis during animal development.

PMID- 30102157
TI  - Heatwaves and health.

PMID- 30102158
TI  - Half measures on children's mental health.

PMID- 30102159
TI  - Vaccine scandal and confidence crisis in China.

PMID- 30102160
TI  - Peer-delivered self-management programmes in mental health.

PMID- 30102161
TI  - Reimagining population health as convergence science.

PMID- 30102162
TI  - Sexual harassment and abuse: when the patient is the perpetrator.

PMID- 30102163
TI  - Women making medical history: introducing A Woman's Place.

PMID- 30102164
TI  - Anna Morandi: anatomist of Enlightenment Bologna.

PMID- 30102165
TI  - In search of lost time.

PMID- 30102166
TI  - Providing quality care on the border with Haiti.

PMID- 30102167
TI  - Reporting of immune checkpoint inhibitor-associated myocarditis.

PMID- 30102168
TI  - Reporting of immune checkpoint inhibitor-associated myocarditis.

PMID- 30102170
TI  - Reporting of immune checkpoint inhibitor-associated myocarditis - Authors' reply.

PMID- 30102169
TI  - Reporting of immune checkpoint inhibitor-associated myocarditis.

PMID- 30102171
TI  - Strategies to correct the shortage of paediatricians in China.

PMID- 30102172
TI  - Department of Error.

PMID- 30102173
TI  - Post-publication peer review and evidence appraisals in primary care.

PMID- 30102175
TI  - A classic case of scurvy.

PMID- 30102176
TI  - Unmet needs of patients with irritable bowel syndrome.

PMID- 30102174
TI  - Peer-supported self-management for people discharged from a mental health crisis
      team: a randomised controlled trial.
AB  - BACKGROUND: High resource expenditure on acute care is a challenge for mental
      health services aiming to focus on supporting recovery, and relapse after an
      acute crisis episode is common. Some evidence supports self-management
      interventions to prevent such relapses, but their effect on readmissions to acute
      care following a crisis is untested. We tested whether a self-management
      intervention facilitated by peer support workers could reduce rates of
      readmission to acute care for people discharged from crisis resolution teams,
      which provide intensive home treatment following a crisis. METHODS: We did a
      randomised controlled superiority trial recruiting participants from six crisis
      resolution teams in England. Eligible participants had been on crisis resolution
      team caseloads for at least a week, and had capacity to give informed consent.
      Participants were randomly assigned to intervention and control groups by an
      unmasked data manager. Those collecting and analysing data were masked to
      allocation, but participants were not. Participants in the intervention group
      were offered up to ten sessions with a peer support worker who supported them in
      completing a personal recovery workbook, including formulation of personal
      recovery goals and crisis plans. The control group received the personal recovery
      workbook by post. The primary outcome was readmission to acute care within 1
      year. This trial is registered with ISRCTN, number 01027104. FINDINGS: 221
      participants were assigned to the intervention group versus 220 to the control
      group; primary outcome data were obtained for 218 versus 216. 64 (29%) of 218
      participants in the intervention versus 83 (38%) of 216 in the control group were
      readmitted to acute care within 1 year (odds ratio 0.66, 95% CI 0.43-0.99;
      p=0.0438). 71 serious adverse events were identified in the trial (29 in the
      treatment group; 42 in the control group). INTERPRETATION: Our findings suggest
      that peer-delivered self-management reduces readmission to acute care, although
      admission rates were lower than anticipated and confidence intervals were
      relatively wide. The complexity of the study intervention limits
      interpretability, but assessment is warranted of whether implementing this
      intervention in routine settings reduces acute care readmission. FUNDING:
      National Institute for Health Research.

PMID- 30102177
TI  - Funding for gastrointestinal disease research in the European Union.

PMID- 30102178
TI  - Future directions in diagnostic gastrointestinal endoscopy.

PMID- 30102179
TI  - Global prevalence of hepatitis B virus infection and prevention of mother-to
      child transmission.

PMID- 30102180
TI  - Global prevalence of hepatitis B virus infection and prevention of mother-to
      child transmission.

PMID- 30102182
TI  - Theodor Billroth: ushering in the modern era.

PMID- 30102181
TI  - Global prevalence of hepatitis B virus infection and prevention of mother-to
      child transmission - Authors' reply.

PMID- 30102183
TI  - Differential diagnosis of inflammatory bowel disease: imitations and
      complications.
AB  - Inflammatory bowel disease (IBD) is characterised by episodes of relapse and
      periods of remission. However, the clinical features, such as abdominal pain,
      diarrhoea, and rectal bleeding, are not specific. Therefore, the differential
      diagnosis can include a broad spectrum of inflammatory or infectious diseases
      that mimic IBD, as well as others that might complicate existing IBD. In this
      Review, we provide an overview of ileocolitis of diverse causes that are relevant
      in the differential diagnosis of IBD. We highlight the importance of accurate
      patient profiling and give a practical approach to identifying factors that
      should trigger the search for a specific cause of intestinal inflammation. Mimics
      of IBD include not only infectious causes of colitis-and particular attention is
      required for patients from endemic areas of tuberculosis-but also vascular
      diseases, diversion colitis, diverticula or radiation-related injuries, drug
      induced inflammation, and monogenic diseases in very-early-onset refractory
      disease. A superinfection with cytomegalovirus or Clostridium difficile can
      aggravate intestinal inflammation in IBD, especially in patients who are
      immunocompromised. Special consideration should be made to the differential
      diagnosis of perianal disease.

PMID- 30102184
TI  - Oesophageal perforation.

PMID- 30102185
TI  - Correction to Lancet Gastroenterol Hepatol 2018; 3: 603-13.

PMID- 30102186
TI  - Intensity Modulated Radiation Therapy Versus Conventional Radiation for Anal
      Cancer in the Veterans Affairs System.
AB  - PURPOSE: Compared with conventional radiation therapy, intensity modulated
      radiation therapy (IMRT) may reduce acute toxicity from anal cancer treatment,
      potentially leading to improved long-term outcomes. We analyze the effect of IMRT
      on short- and long-term outcomes among a large sample of US veterans. METHODS AND
      MATERIALS: From a national Veterans Affairs database, we identified 779 patients
      (n = 403 conventional radiation therapy, n = 376 IMRT) with locally advanced anal
      squamous cell carcinoma diagnosed between 2000 and 2015 and treated with
      concurrent chemoradiation therapy. Radiation treatment planning and dosimetric
      constraints were not standardized across patients. We analyzed the effect of IMRT
      on short-term outcomes (acute toxicity, treatment breaks, and incomplete
      chemotherapy) and long-term outcomes (survival and ostomy placement) in
      multivariable logistic regression, Fine-Gray, and frailty models, adjusting for
      potential confounders. RESULTS: IMRT was associated with decreased radiation
      treatment breaks >=5 days (odds ratio [OR] 0.58; 95% confidence interval [CI]
      0.37-0.91; P = .02), increased rates of receiving 2 cycles of mitomycin C
      chemotherapy (OR 2.04; 95% CI 1.22-3.45; P = .007), increased rates of receiving
      2 cycles of any chemotherapy (OR 3.45; 95% CI 1.82-6.25; P < .001), and decreased
      risk of ostomy related to tumor recurrence or progression (subdistribution hazard
      ratio 0.60; 95% CI 0.37-0.99; P = .045). IMRT was not associated with a decrease
      in grade 3 to 4 hematologic toxicity (P = .79), hospitalization for
      gastrointestinal toxicity (P = .59), or cancer-specific survival (P = 0.18).
      CONCLUSIONS: Among a large sample of US veterans with anal cancer, IMRT was
      associated with higher rates of receiving 2 chemotherapy cycles, decreased
      radiation treatment breaks, and decreased rates of ostomy placement. IMRT appears
      to offer substantial benefits over conventional radiation therapy for patients
      undergoing concurrent chemoradiation therapy for anal cancer.

PMID- 30102187
TI  - Challenging Case: Mediastinal Mammary Malignancy.

PMID- 30102189
TI  - Systemic Therapy with Radiation to the Chest Wall Alone.

PMID- 30102188
TI  - Comparison of Patient-reported Outcomes After External Beam Radiation Therapy and
      Combined External Beam With Low-dose-rate Brachytherapy Boost in Men With
      Localized Prostate Cancer.
AB  - PURPOSE: To compare patient-reported disease-specific functional outcomes after
      external beam radiation therapy (EBRT) and EBRT combined with low-dose-rate
      brachytherapy prostate boost (EB-LDR) among men with localized prostate cancer.
      METHODS AND MATERIALS: The prospective, population-based Comparative
      Effectiveness Analysis of Surgery and Radiation study enrolled men with localized
      prostate cancer in 2011 to 2012. The 26-item Expanded Prostate Cancer Index
      Composite measured patient-reported disease-specific function at baseline and at
      6, 12, and 36 months. Higher domain scores indicate better function. Minimal
      clinically important difference was defined as 6 for urinary incontinence, 5 for
      urinary irritative function, 4 for bowel function, 12 for sexual function, and 4
      for hormonal function. Multivariable linear and logistic regression models were
      fit to estimate the effect of treatment on patient-reported outcomes. RESULTS:
      Five-hundred seventy-eight men received EBRT and 109 received EB-LDR. Median
      patient age was 69 years, and 70% had intermediate- or high-risk disease. Men in
      the EB-LDR group were younger (P < .001) and less likely to receive androgen
      deprivation therapy (P < .001). Baseline urinary, bowel, sexual, and hormonal
      function was similar between treatment groups (P > .05). On multivariable
      analyses, men receiving EB-LDR reported worse urinary irritative function at 6
      months (adjusted mean difference [AMD] -14.4, P < .001), 12 months (AMD -12.9, P
      < .001), and 36 months (AMD -4.7, P = .034) than men receiving EBRT. At 12
      months, men receiving EB-LDR reported worse bowel function (AMD -5.8, P = .002),
      but these differences were not seen at 36 months. There were no significant
      differences in sexual or hormone function between treatment groups. CONCLUSIONS:
      Men treated with EB-LDR report worse bowel function at 1 year and worse urinary
      irritative function through 3 years compared with men treated with EBRT alone.
      These side effect profiles should be discussed with patients when considering EB
      LDR versus EBRT treatment.

PMID- 30102190
TI  - Putting the "BR" in SBRT.

PMID- 30102191
TI  - Aggressive Systemic Therapy with Response-Based Radiation.

PMID- 30102192
TI  - A Fellow's Fate: Employment Outcomes of Radiation Oncology Fellowship Graduates.

PMID- 30102193
TI  - Pediatric Localized Intracranial Ependymomas: A Multicenter Analysis of the
      Societe Francaise de lutte contre les Cancers de l'Enfant (SFCE) from 2000 to
      2013.
AB  - PURPOSE: The objective of this study was to analyze survival and prognostic
      factors for children, adolescents, and young adults treated with postoperative
      radiation therapy (RT) for intracranial ependymoma. METHODS AND MATERIALS:
      Between 2000 and 2013, 202 patients aged <=25 years were treated in the 13 main
      French pediatric RT reference centers. Their medical records were reviewed for
      information, treatments received, and survival rates. All children had received
      postoperative RT- conformal, intensity modulated, or proton beam. In 2009, the
      prescribed standard dose in France rose from 54 Gy to 59.4 Gy. RESULTS: Median
      follow-up was 53.8 months (95% confidence interval [CI] 47-63.5). Median age at
      RT was 5 years (range 1-22), and 32% of the children treated were aged <3 years.
      Regarding treatment, 85.6% of patients underwent gross total resection, 62% of
      patients received conformal RT (vs 29% for intensity modulated RT and 8% for
      proton beam RT), 62.4% of patients received a dose >54 Gy, and 71% received
      chemotherapy. Of the 84 relapses, 75% were local. The cumulative incidence of
      local relapse was 24.4% (95% CI 18.2-31.2) at 3 years and 31.3% (95% CI 24-38.9)
      at 5 years. The 5-year disease-free survival (DFS) and overall survival rates
      were 50.4% (95% CI 42.2-58) and 71.4% (95% CI 63.1-78.2). Tumor grade was the
      only prognostic factor for local relapse and DFS. Tumor grade, age, and extent of
      resection were independent prognostic factors for overall survival. CONCLUSIONS:
      We confirmed several clinical and tumoral prognostic factors in a large French
      multicenter study. DFS for intracranial ependymoma remains low, and new
      biological and imaging markers are needed to distinguish among different
      subtypes, adapt treatments, and improve survival.

PMID- 30102195
TI  - Outcomes for Cervical Cancer Patients Treated With Radiation in High-Volume and
      Low-Volume Hospitals.
AB  - PURPOSE: To investigate the effects of different hospital patient loads on the
      standard of care and treatment outcomes of patients with cervical cancer treated
      primarily with radiation therapy and to identify factors that may contribute to
      survival differences among hospitals. METHODS AND MATERIALS: We used the Taiwan
      Cancer Registry database to extract data on a total of 2582 International
      Federation of Gynecology and Obstetrics stage IB to IVA patients with uterine
      cervical cancer diagnosed from 2007 to 2013 who underwent primarily curative
      radiation therapy (with or without chemotherapy). We explored associations among
      hospital patient loads, clinical parameters, the type of care given, and
      survival. RESULTS: Patients who received treatment at hospitals with small and
      medium patient loads (<=5 cases annually) were older and had more advanced-stage
      disease than other patients. Positive associations were evident between the use
      of chemotherapy and brachytherapy and hospital patient load. Patients treated at
      hospitals with large patient loads (>5 cases annually) experienced better overall
      survival than those treated at hospitals with small or medium patient loads (P <
      .001). Stepwise addition of variables to multivariable analyses indicated that
      greater use of chemotherapy and brachytherapy were major contributors to the
      better survival of patients treated at hospitals with large patient loads.
      However, larger hospital patient load per se (>5 vs <=5 cases annually) was also
      independently prognostic for better survival of patients with bulky tumors or
      advanced-stage disease. CONCLUSIONS: We found that the inferior survival rate of
      patients with cervical cancer treated at hospitals with smaller patient loads was
      attributable not only to a lower standard of care in such hospitals but also to
      the smaller patient load. Our findings indicate how treatment should be improved
      in hospitals with small and medium patient loads.

PMID- 30102197
TI  - Error Detection in Intensity-Modulated Radiation Therapy Quality Assurance Using
      Radiomic Analysis of Gamma Distributions.
AB  - PURPOSE: To improve the detection of errors in intensity-modulated radiation
      therapy (IMRT) with a novel method that uses quantitative image features from
      radiomics to analyze gamma distributions generated during patient specific
      quality assurance (QA). METHODS AND MATERIALS: One hundred eighty-six IMRT beams
      from 23 patient treatments were delivered to a phantom and measured with
      electronic portal imaging device dosimetry. The treatments spanned a range of
      anatomic sites; half were head and neck treatments, and the other half were drawn
      from treatments for lung and rectal cancers, sarcoma, and glioblastoma. Planar
      gamma distributions, or gamma images, were calculated for each beam using the
      measured dose and calculated doses from the 3-dimensional treatment planning
      system under various scenarios: a plan without errors and plans with either
      simulated random or systematic multileaf collimator mispositioning errors. The
      gamma images were randomly divided into 2 sets: a training set for model
      development and testing set for validation. Radiomic features were calculated for
      each gamma image. Error detection models were developed by training logistic
      regression models on these radiomic features. The models were applied to the
      testing set to quantify their predictive utility, determined by calculating the
      area under the curve (AUC) of the receiver operator characteristic curve, and
      were compared with traditional threshold-based gamma analysis. RESULTS: The AUC
      of the random multileaf collimator mispositioning model on the testing set was
      0.761 compared with 0.512 for threshold-based gamma analysis. The AUC for the
      systematic mispositioning model was 0.717 versus 0.660 for threshold-based gamma
      analysis. Furthermore, the models could discriminate between the 2 types of
      errors simulated here, exhibiting AUCs of approximately 0.5 (equivalent to random
      guessing) when applied to the error they were not designed to detect.
      CONCLUSIONS: The feasibility of error detection in patient-specific IMRT QA using
      radiomic analysis of QA images has been demonstrated. This methodology represents
      a substantial step forward for IMRT QA with improved sensitivity and specificity
      over current QA methods and the potential to distinguish between different types
      of errors.

PMID- 30102196
TI  - Body Mass Index as a Prognostic Marker in Glioblastoma Multiforme: A Clinical
      Outcome.
AB  - PURPOSE: Correlation of body mass index (BMI) with clinical outcome in patients
      with glioblastoma is not well documented. Hence, we studied the association
      between survival and pretreatment BMI in glioblastoma patients. METHODS AND
      MATERIALS: In this retrospective study, only patients with histopathology
      confirmed glioblastoma were included. Their BMIs were calculated from height and
      weight measurements and recorded in medical records at their first examination.
      Treatment plans for all patients consisted of concurrent radiation therapy and
      temozolomide, followed by maintenance therapy with temozolomide. The primary
      endpoint was overall survival (OS). Univariate and multivariate Cox proportional
      hazards models were used to estimate the mortality risk associated with BMI as a
      continuous and categorical variable. A BMI of 18.5 to 24.9 kg/m2 was classified
      as normal, 25.0 to 29.9 kg/m2 as overweight, and >=30.0 kg/m2 as obese. RESULTS:
      Data from 392 patients treated from January 2008 through June 2016 were analyzed.
      At a median follow-up of 48.6 months, the median OS was 13.5 months in normal
      subjects, 15.4 months in overweight subjects, and 15.1 months in obese subjects.
      A total of 81% of the patients died. The hazard ratios for overweight and obese
      patients were 0.70 (95% confidence interval, 0.54-0.92; P = .009) and 0.66 (95%
      confidence interval, 0.45-0.98; P = .04), respectively, when adjusted for age,
      Karnofsky performance score, and extent of resection. Sex, diabetes, and
      hypertension had no significant interactions. CONCLUSIONS: Patients with elevated
      BMIs had significantly better OS in our series of patients. The mechanism of this
      interaction needs to be explored further to understand this association.

PMID- 30102198
TI  - In Regard to Beadle and Anderson.

PMID- 30102194
TI  - High Single Doses of Radiation May Induce Elevated Levels of Hypoxia in Early
      Stage Non-Small Cell Lung Cancer Tumors.
AB  - PURPOSE: Tumor hypoxia correlates with treatment failure in patients undergoing
      conventional radiation therapy. However, no published studies have investigated
      tumor hypoxia in patients undergoing stereotactic body radiation therapy (SBRT).
      We aimed to noninvasively quantify the tumor hypoxic volume (HV) in non-small
      cell lung cancer (NSCLC) tumors to elucidate the potential role of tumor vascular
      response and reoxygenation at high single doses. METHODS AND MATERIALS: Six SBRT
      eligible patients with NSCLC tumors >1 cm were prospectively enrolled in an
      institutional review board-approved study. Dynamic positron emission tomography
      images were acquired at 0 to 120 minutes, 150 to 180 minutes, and 210 to 240
      minutes after injection of 18F-fluoromisonidazole. Serial imaging was performed
      prior to delivery of 18 Gy and at approximately 48 hours and approximately 96
      hours after SBRT. Tumor HVs were quantified using the tumor-to-blood ratio (>1.2)
      and rate of tracer influx (>0.0015 mL.min.cm-3). RESULTS: An elevated and in some
      cases persistent level of tumor hypoxia was observed in 3 of 6 patients. Two
      patients exhibited no detectable baseline tumor hypoxia, and 1 patient with high
      baseline hypoxia only completed 1 imaging session. On the basis of the tumor-to
      blood ratio, in the remaining 3 patients, tumor HVs increased on day 2 after 18
      Gy and then showed variable responses on day 4. In the 3 of 6 patients with
      detectable hypoxia at baseline, baseline tumor HVs ranged between 17% and 24%
      (mean, 21%), and HVs on days 2 and 4 ranged between 33% and 45% (mean, 40%) and
      between 18% and 42% (mean, 28%), respectively. CONCLUSIONS: High single doses of
      radiation delivered as part of SBRT may induce an elevated and in some cases
      persistent state of tumor hypoxia in NSCLC tumors. Hypoxia imaging with 18F
      fluoromisonidazole positron emission tomography should be used in a larger cohort
      of NSCLC patients to determine whether elevated tumor hypoxia is predictive of
      treatment failure in SBRT.

PMID- 30102199
TI  - Erratum to: Schreibmann E, Schuster D, Rossi P, et al. Image Guided Planning for
      Prostate Carcinomas With Incorporation of Anti-3-[18F]FACBC (Fluciclovine)
      Positron Emission Tomography: Workflow and Initial Findings From a Randomized
      Trial. Int J Radiat Oncol Biol Phys 2016;96:206-213.

PMID- 30102200
TI  - Erratum to: Ho AY, Olm-Shipman M, Zhang Z, et al. A Randomized Trial of
      Mometasone Furoate 0.1% to Reduce High Grade Acute Radiation Dermatitis in Breast
      Cancer Patients Receiving Postmastectomy Radiation. Int J Radiat Oncol Biol Phys
      2018;101;325-333.

PMID- 30102201
TI  - Content Validity of Anatomic Site-Specific Patient-Reported Outcomes Version of
      the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Item Sets for
      Assessment of Acute Symptomatic Toxicities in Radiation Oncology.
AB  - PURPOSE: To improve assessment of symptomatic toxicity in cancer clinical trials
      and complement clinician-based toxicity reporting, the US National Cancer
      Institute developed a measurement system called the Patient-Reported Outcomes
      version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). The
      objective of this study was to examine the content validity of PRO-CTCAE in
      patients undergoing radiation therapy and to establish anatomic site-specific
      item sets for implementation in cancer research. METHODS AND MATERIALS: Patients
      receiving radiation to the brain, head and neck, breast, thorax, abdomen, or
      pelvis were recruited during the final week of radiation. Participants described
      side effects qualitatively and completed anatomic site-specific checklists
      indicating the presence or absence of symptomatic toxicities drawn from the PRO
      CTCAE library. Items endorsed by >=20% of participants were selected for
      inclusion. Symptomatic toxicities described qualitatively were content analyzed
      and summarized. Symptomatic toxicities not reflected in the PRO-CTCAE item
      library were tabulated. RESULTS: We conducted 389 interviews of patients
      receiving radiation to the brain (n = 46), head and neck (n = 69), breast (n =
      134), thorax (n = 30), abdomen (n = 27), female pelvis (n = 36), or male pelvis
      (n = 47). Median age was 62 years; 62% were female. The 53 solicited PRO-CTCAE
      symptoms reflected all reported radiation-induced toxicities with the exception
      of phlegm/mucus production and mouth/throat pain with swallowing in patients
      receiving head and neck radiation, eye dryness/irritation in patients undergoing
      brain radiation, and obstructive urinary symptoms in men receiving pelvic
      radiation. The PRO-CTCAE items "skin burns" and "pain" require greater
      specificity to adequately reflect toxicities experienced during radiation.
      CONCLUSIONS: PRO-CTCAE demonstrates strong content validity as a measure of
      symptomatic toxicities in patients receiving radiation. These results provide
      empirical support for the definition of site-specific PRO-CTCAE item sets to
      assess the symptomatic toxicities of radiation therapy. The site-specific PRO
      CTCAE item sets developed herein are currently being deployed in our department
      via an electronic platform to capture treatment-related toxicity.

PMID- 30102202
TI  - Radiation Oncology in Mexico: Toward a Unified Model.

PMID- 30102203
TI  - Radiation in Central Nervous System Leukemia: Guidelines From the International
      Lymphoma Radiation Oncology Group.

PMID- 30102204
TI  - Consolidative Whole-Brain Radiation Therapy Versus Autologous Stem Cell
      Transplant for Primary Central Nervous System Lymphoma: A Large Dose of
      Perspective and Perhaps a Lower Dose of Radiation Are in Order.

PMID- 30102206
TI  - Radiation Therapy Field Design and Lymphedema Risk After Regional Nodal
      Irradiation for Breast Cancer.
AB  - PURPOSE: The occurrence of upper extremity lymphedema after regional nodal
      irradiation (RNI) for breast cancer treatment varies significantly based on
      patient and treatment factors. The relationship between the radiation therapy
      (RT) field design and lymphedema risk is not well-characterized. The present
      study sought to correlate the variations in RT field design with lymphedema
      outcomes. METHODS AND MATERIALS: Women with stage II-IV breast cancer receiving
      RNI after breast surgery that included sentinel lymph node biopsy or axillary
      dissection were identified. Their arm circumference was measured before RT and at
      each follow-up visit to assess for lymphedema. Nodal RT fields were defined using
      a trifurcated system. Group 1 excluded the upper level I and II axilla, defined
      by the lateral border of the nodal field encompassing less than one-third of the
      humeral head. Group 2 included the upper level I and II axilla, defined by the
      lateral border of the nodal field encompassing more than one-third of the humoral
      head treated with an anterior oblique beam. Group 3 included the upper level I
      and II axilla the same as for group 2 but with parallel-opposed beams delivering
      a significant dose to the musculature posterior to the axilla. RESULTS: From 1999
      to 2013, 526 women received RNI. The median post-RT follow-up was 5.5 years. For
      the 492 women meeting the inclusion criteria, the cumulative incidence of
      lymphedema was 23.5% at 2 years and 31.8% at 5 years. On univariate analysis, the
      patients in group 1 had a lower 5-year lymphedema rate (7.7%) than those in group
      2 (37.1%) and group 3 (36.7%; P < .0001). On multivariate analysis, inclusion of
      the upper level I and II axilla (groups 2 and 3) remained significantly
      associated with increased lymphedema risk. CONCLUSIONS: Variations in the RT
      field design significantly affect the development of lymphedema after RNI. In
      particular, the upper level I and II axilla appear to be important regions for
      lymphedema risk after axillary dissection.

PMID- 30102207
TI  - Lymphedema: Time for an Update.

PMID- 30102205
TI  - Phase 2 Study of First-line Intensity Modulated Radiation Therapy Followed by
      Gemcitabine, Dexamethasone, and Cisplatin for High-Risk, Early Stage Extranodal
      Nasal-Type NK/T-Cell Lymphoma: The GREEN Study.
AB  - PURPOSE: To investigate the efficacy and toxicity profile of sequential intensity
      modulated radiation therapy (IMRT) followed by gemcitabine, dexamethasone, and
      cisplatin (GDP) on previously untreated high-risk, early stage upper
      aerodigestive tract natural killer/T-cell lymphoma (UADT-NKTCL). METHODS AND
      MATERIALS: A phase 2 study was designed, and 40 high-risk patients with stage
      I(E)/II(E) UADT-NKTCL were enrolled between June 2010 and June 2014. High-risk
      patients were defined as those with at least 1 predefined risk factor: age >60
      years, elevated serum lactate dehydrogenase, regional lymph node involvement, B
      symptoms, and primary tumor invasion. Patients received extended involved-site
      IMRT and GDP chemotherapy. The primary endpoint was the 2-year progression-free
      survival rate. Secondary endpoints were the 2-year overall survival rate, overall
      response rate, and toxicity. RESULTS: Median follow-up time was 60.1 months. The
      overall response rate and complete remission rate were 97.5% and 95.0%,
      respectively. The 2- and 5-year progression-free survival rates were 84.7% and
      79.4%, and the corresponding overall survival rates were 89.9% and 82.1%,
      respectively. The most frequent radiation-induced toxicities were mild mucositis
      and skin reaction. Grade 3/4 neutropenia (12 of 40 patients), thrombocytopenia (7
      of 40), and anemia (2 of 40) were observed during chemotherapy. CONCLUSIONS:
      First-line IMRT followed by GDP represents an effective and well-tolerated
      protocol for high-risk, early stage UADT-NKTCL.

PMID- 30102208
TI  - Analysis of Skin Flap Thickness and Residual Breast Tissue After Mastectomy.
AB  - PURPOSE: Residual breast tissue (RBT) after mastectomy represents an unknown risk
      for local recurrence or development of a new cancer and affects decisions
      regarding adjuvant radiation therapy. This study used breast magnetic resonance
      imaging to evaluate the frequency of RBT and provide average thickness skin flap
      measurements in patients with total mastectomy, skin-sparing mastectomy, and
      nipple-sparing mastectomy (NSM) followed by breast reconstruction. METHODS AND
      MATERIALS: We carried out a retrospective analysis of 7432 consecutive
      postoperative breast magnetic resonance imaging examinations performed between
      August 2008 and July 2013, selecting 367 women (mean +/- standard deviation age,
      46.7 +/- 8.7 years) who had undergone therapeutic or prophylactic mastectomy with
      reconstruction, for a total of 501 cases. The variables analyzed included
      fibroglandular tissue presence, skin flap thickness at 11 pre-established points,
      age, weight, height, body mass index, laterality, surgical indication, surgery
      type, reconstruction type, adjuvant therapy, and cancer treatment history.
      Statistical analyses were descriptive and comparative and included logistic
      regression models (P < .05). RESULTS: At 9 of the 11 points of measure, the
      median thickness of the flap exceeded 5.5 mm. Excluding the areolar region, RBT
      was identified in 29.9% of the cases: 21.3% of the therapeutic mastectomy cases
      and 51% of the NSM cases. The variables independently associated with the
      presence of RBT were flap thickness (P < .001), patient height (P < .03),
      mastectomy indication (P < .001), mastectomy type (P < .012 for skin-sparing
      mastectomy and P < .001 for NSM and total mastectomy), and breast reconstruction
      with flap (P < .019). CONCLUSIONS: All forms of mastectomy leave RBT. Our study
      has demonstrated that the RBT amount can be variable and quite prevalent. Because
      of the low quality of the evidence to ensure the oncological safety of sparing
      mastectomies, we suggest that knowledge of the extent of the remaining breast
      tissue is important for guiding additional surveillance and therapeutic
      interventions, including radiation therapy.

PMID- 30102209
TI  - When treatment does not work: failure to understand failure.

PMID- 30102210
TI  - A roadmap for restoring trust in Big Data.

PMID- 30102211
TI  - Lung cancer in the UK: addressing geographical inequality and late diagnosis.

PMID- 30102212
TI  - Knowledge-based drug discovery intensifies private appropriation of publicly
      financed research.

PMID- 30102213
TI  - Breast cancer in a Renaissance Book of the Dead.

PMID- 30102214
TI  - A virtual musician quartet with vestibular schwannoma.

PMID- 30102215
TI  - Digital oncology apps: revolution or evolution?

PMID- 30102216
TI  - Omitting radiosurgery in melanoma brain metastases: a drastic and dangerous de
      escalation.

PMID- 30102217
TI  - Omitting radiosurgery in melanoma brain metastases: a drastic and dangerous de
      escalation - Authors' reply.

PMID- 30102218
TI  - Gastrointestinal cancers in patients with cystic fibrosis.

PMID- 30102219
TI  - Gastrointestinal cancers in patients with cystic fibrosis - Authors' reply.

PMID- 30102220
TI  - CXCR4-targeted therapy in breast cancer.

PMID- 30102221
TI  - [177Lu]-PSMA-617 radionuclide therapy in patients with metastatic castration
      resistant prostate cancer.

PMID- 30102222
TI  - [177Lu]-PSMA-617 radionuclide therapy in patients with metastatic castration
      resistant prostate cancer.

PMID- 30102223
TI  - [177Lu]-PSMA-617 radionuclide therapy in patients with metastatic castration
      resistant prostate cancer - Author's reply.

PMID- 30102224
TI  - Sex as a predictor of response to cancer immunotherapy.

PMID- 30102225
TI  - Sex as a predictor of response to cancer immunotherapy.

PMID- 30102226
TI  - Sex as a predictor of response to cancer immunotherapy.

PMID- 30102227
TI  - Sex as a predictor of response to cancer immunotherapy.

PMID- 30102228
TI  - Sex as a predictor of response to cancer immunotherapy.

PMID- 30102229
TI  - Sex as a predictor of response to cancer immunotherapy.

PMID- 30102231
TI  - Correction to Lancet Oncol 2018; 19: 953-64.

PMID- 30102230
TI  - Sex as a predictor of response to cancer immunotherapy - Authors' reply.

PMID- 30102232
TI  - Correction to Lancet Oncol 2018; 19: 1040-50.

PMID- 30102233
TI  - Correction to Lancet Oncol 2018; 19: 1019-20.

PMID- 30102235
TI  - Cognitive functioning and health-related quality of life in patients with newly
      diagnosed primary CNS lymphoma: a systematic review.
AB  - Incidence of primary CNS lymphoma (PCNSL) is increasing, while prognosis is
      improving as treatments advance. However, declined cognitive functioning remains
      a major challenge in the treatment of PCNSL. This cognitive decline, in
      conjunction with other symptoms caused by the disease or its treatment, or both,
      can compromise health-related quality of life (HRQOL). The aim of this Review was
      to give a comprehensive overview on cognitive functioning and HRQOL for patients
      with PCNSL, including an evaluation of patient-related and treatment-related
      factors that can influence cognitive functioning and HRQOL. We reviewed the
      literature for studies on cognitive functioning and HRQOL in newly diagnosed
      adult patients with PCNSL using MEDLINE/PubMed, Embase, Web of Science, Scopus,
      Cochrane, PsycINFO, CINAHL EBSCO, and Google Scholar, up to Jan 4, 2018. Articles
      were selected using predetermined inclusion and exclusion criteria; 42 articles
      were eligible for inclusion. Findings show that the tumour itself has a great
      effect on cognitive functioning and HRQOL. Initially, induction chemotherapy
      results in improvement of cognition and HRQOL in most patients. In the long-term,
      the addition of whole-brain radiotherapy has a negative effect on cognitive
      functioning, but the magnitude of this effect is not always clinically relevant.
      HRQOL scores were worse compared with controls, and worse after combined
      chemotherapy and radiotherapy when compared with chemotherapy only, particularly
      in the long term. Therefore, combined chemotherapy and radiotherapy seems to have
      a negative effect on HRQOL and cognition in patients with PCNSL. Although
      prolonged progression-free survival is achieved with combined treatment,
      information on its effect on cognition and HRQOL should be included in clinical
      decision-making.

PMID- 30102234
TI  - Developing institutions for cancer care in low-income and middle-income
      countries: from cancer units to comprehensive cancer centres.
AB  - Global cancer centres operate across different sizes, scales, and ecosystems.
      Understanding the essential aspects of the creation, organisation, accreditation,
      and activities within these settings is crucial for developing an affordable,
      equitable, and quality cancer care, research, and education system. Robust
      guidelines are scarce for cancer units, cancer centres, and comprehensive cancer
      centres in low-income and middle-income countries. However, some robust examples
      of the delivery of complex cancer care in centres in emerging economies are
      available. Although it is impossible to create an optimal system to fit the
      unique needs of all countries for the delivery of cancer care, we summarise what
      has been published about the development and management of cancer centres in low
      income and middle-income countries so far and highlight the need for clinical and
      political leadership.

PMID- 30102237
TI  - Adrenocortical carcinoma misdiagnosed as hepatocellular carcinoma.

PMID- 30102236
TI  - Biological material collection to advance translational research and treatment of
      children with CNS tumours: position paper from the SIOPE Brain Tumour Group.
AB  - Paediatric CNS tumours are the most common cause of childhood cancer-related
      morbidity and mortality, and improvements in their diagnosis and treatment are
      needed. New genetic and epigenetic information about paediatric CNS tumours is
      transforming the field dramatically. For most paediatric CNS tumour entities,
      subgroups with distinct biological characteristics have been identified, and
      these characteristics are increasingly used to facilitate accurate diagnoses and
      therapeutic recommendations. Future treatments will be further tailored to
      specific molecular subtypes of disease, specific tumour predisposition syndromes,
      and other biological criteria. Successful biomaterial collection is a key
      requirement for the application of contemporary methodologies for the validation
      of candidate prognostic factors, the discovery of new biomarkers, the
      establishment of appropriate preclinical research models for targeted agents, a
      quicker clinical implementation of precision medicine, and for other therapeutic
      uses (eg, for immunotherapies). However, deficits in organisational structures
      and interdisciplinary cooperation are impeding the collection of high-quality
      biomaterial from CNS tumours in most centres. Practical, legal, and ethical
      guidelines for consent, storage, material transfer, biobanking, data sharing, and
      funding should be established by research consortia and local institutions to
      allow optimal collection of primary and subsequent tumour tissue, body fluids,
      and normal tissue. Procedures for the collection and storage of biomaterials and
      related data should be implemented according to the individual and organisational
      structures of the local institutions.

PMID- 30102238
TI  - Inpatient and Outpatient Wound Treatment Recommendations: Assessing Use of
      Negative Pressure Wound Therapy Systems or Oxidized Regenerated Cellulose (ORC)/
      Collagen/Silver-ORC Dressings.
AB  - The increase in wound prevalence means more patients with wounds are being
      transferred through care settings than ever before. Although the goals of therapy
      may be the same in both settings, wound care therapies and dressings differ in
      availability and appropriateness for each setting. Negative pressure wound
      therapy (NPWT) modalities and oxidized regenerated cellulose (ORC)/collagen
      (C)/silver-ORC dressings are available in both inpatient and outpatient care
      settings, but (to-date) lack comprehensive information regarding best practices
      in transitioning use of these therapies between various care settings. A panel
      meeting was convened to provide literature- and experience-based recommendations
      in transitioning wound care patients between various care settings. The use of
      NPWT with instillation and dwell time was recommended in wounds contaminated with
      debris and/or infectious materials or heavy exudate. In addition, ORC/C/silver
      ORC dressing application was recommended for surface bleeding and for placement
      into explored areas of undermining to help promote development of granulation
      tissue. When transitioning a patient from inpatient to outpatient care, overall
      health, access to services, severity and complexity of the wound, and equipment
      availability should be taken into consideration. Treatment modalities to bridge
      the gap during care transition should be used to help maintain continuous care.
      For outpatient care, NPWT use was recommended for removal of infectious materials
      and exudate management. The ORC/C/silver-ORC dressings also may be used to help
      manage exudate and promote granulation tissue development and moist wound
      healing. In addition, practice challenges and potential solutions for patient
      adherence, interrupted care during patient transition, and troubleshooting after
      hours and weekend device alarms were discussed.

PMID- 30102239
TI  - Multi-stage SVM approach for cardiac arrhythmias detection in short single-lead
      ECG recorded by a wearable device.
AB  - OBJECTIVE: Use of wearable ECG devices for arrhythmia screening is limited due to
      poor signal quality, small number of leads and short records, leading to
      incorrect recognition of pathological events. This paper introduces a novel
      approach to classification (normal/'N', atrial fibrillation/'A', other/'O', and
      noisy/'P') of short single-lead ECGs recorded by wearable devices. APPROACH:
      Various rhythm and morphology features are derived from the separate beats
      ('local' features) as well as the entire ECGs ('global' features) to represent
      short-term events and general trends respectively. Various types of atrial and
      ventricular activity, heart beats and, finally, ECG records are then recognised
      by a multi-level approach combining a support vector machine (SVM), decision tree
      and threshold-based rules. MAIN RESULTS: The proposed features are suitable for
      the recognition of 'A'. The method is robust due to the noise estimation
      involved. A combination of radial and linear SVMs ensures both high predictive
      performance and effective generalisation. Cost-sensitive learning, genetic
      algorithm feature selection and thresholding improve overall performance. The
      generalisation ability and reliability of this approach are high, as verified by
      cross-validation on a training set and by blind testing, with only a slight
      decrease of overall F1-measure, from 0.84 on training to 0.81 on the tested
      dataset. 'O' recognition seems to be the most difficult (test F1-measures:
      0.90/'N', 0.81/'A' and 0.72/'O') due to high inter-patient variability and
      similarity with 'N'. SIGNIFICANCE: These study results contribute to
      multidisciplinary areas, focusing on creation of robust and reliable cardiac
      monitoring systems in order to improve diagnosis, reduce unnecessary time
      consuming expert ECG scoring and, consequently, ensure timely and effective
      treatment.

PMID- 30102240
TI  - Exploration and application of phenomenological RBE models for proton therapy.
AB  - The relative biological effectiveness (RBE) of protons varies with multiple
      physical and biological factors. Phenomenological RBE models have been developed
      to include such factors in the estimation of a variable RBE, in contrast to the
      clinically applied constant RBE of 1.1. In this study, eleven published
      phenomenological RBE models and two plan-based models were explored and applied
      to simulated patient cases. All models were analysed with respect to the
      distribution and range of linear energy transfer (LET) and reference radiation
      fractionation sensitivity ((alpha/beta) x ) of their respective experimental
      databases. Proton therapy plans for a spread-out Bragg peak in water and three
      patient cases (prostate adenocarcinoma, pituitary adenoma and thoracic sarcoma)
      were optimised using an RBE of 1.1 in the EclipseTM treatment planning system
      prior to recalculation and modelling in the FLUKA Monte Carlo code. Model
      estimated dose-volume parameters for the planning target volumes (PTVs) and
      organs at risk (OAR) were compared. The experimental in vitro databases for the
      various models differed greatly in the range of (alpha/beta) x values and dose
      averaged LET (LETd). There were significant variations between the model
      estimations, which arose from fundamental differences in the database definitions
      and model assumptions. The greatest variations appeared in organs with low
      (alpha/beta) x and high LETd, e.g. biological doses given to late responding OARs
      located distal to the target in the treatment field. In general, the variation in
      maximum dose (D2%) was larger than the variation in mean dose and other dose
      metrics, with D2% of the left optic nerve ((alpha/beta) x   =  2.1 Gy) in the
      pituitary adenoma case showing the greatest discrepancies between models: 28-52
      Gy(RBE), while D2% for RBE1.1 was 30 Gy(RBE). For all patient cases, the
      estimated mean RBE to the PTV was in the range 1.09-1.29 ((alpha/beta) x   = 
      1.5/3.1/10.6 Gy). There were considerable variations between the estimations of
      RBE and RBE-weighted doses from the different models. These variations were a
      consequence of fundamental differences in experimental databases, model
      assumptions and regression techniques. The results from the implementation of RBE
      models in dose planning studies should be evaluated in light of these deviations.

PMID- 30102241
TI  - Forcing substitution of tantalum by copper in 1T-TaS2: synthesis, structure and
      electronic properties of 1T-Cu x Ta1-x S2.
AB  - We investigated the compound 1T-Cu x Ta1-x S2 with respect to its synthesis,
      homogeneity range, structure and electronic properties. The average structure of
      1T-Cu x Ta1-x S2 resembles that of the high-temperature phase of the layered
      transition metal dichalcogenide 1T-TaS2 in which tantalum is partially
      substituted by copper. 1T-Cu x Ta1-x S2 readily decomposes at elevated
      temperatures and can only be prepared and stabilized by a sufficiently high
      amount of sulfur excess. XPS and NEXAFS measurements reveal that copper has the
      oxidation state  +I in 1T-Cu x Ta1-x S2, which is supported by quantum chemical
      calculations. The disorder introduced by copper doping causes an Anderson-type
      localization of the conduction electrons as manifested by a strong increase of
      the electrical resistivity and a Curie-type paramagnetism at low temperatures as
      in other doped systems 1T-M x Ta1-x S2 with higher valent metals. Quantum
      chemical calculations support this interpretation.

PMID- 30102242
TI  - Novel ZnO/NiO Janus-like nanofibers for effective photocatalytic degradation.
AB  - In recent years, Janus materials have become a research hotspot in the field of
      materials science; however, fabricating inorganic Janus-like nanofibers (NFs) is
      still a challenge. Herein, we report novel ZnO/NiO Janus-like NFs with efficient
      photocatalytic performance via an electrospinning method followed by calcination
      treatment. The morphology, structure, chemical composition and crystallinity of
      ZnO/NiO Janus-like NFs were studied in detail via SEM, TEM, HRTEM, EDS, FT-IR,
      XPS and XRD, indicating that the NFs had a perfect Janus-like structure composed
      of ZnO and NiO. A series of photocatalytic experiments were carried out in
      aqueous organic dye solutions under 365 nm UV radiation for 1 h, with the
      degradation rate of malachite green able to reach 96%, proving that the NFs have
      great potential in the field of organic dye degradation. Furthermore, a
      reasonable catalytic mechanism for the ZnO/NiO Janus-like NFs was proposed, which
      was discussed from the view of electron-hole pairs and p-n junctions. In short,
      the method in our work is expected to become a new way of effectively preparing
      functional inorganic Janus-like NFs.

PMID- 30102243
TI  - Mechanical properties of pristine and defective carbon-phosphide monolayers: a
      density functional tight-binding study.
AB  - Using density functional tight-binding theory, we investigated the elastic
      properties and deformation and failure behaviors of pristine and defective carbon
      phosphide (CP) monolayers subjected to uniform uniaxial tensile strain along arm
      chair (AC) and zig-zag (ZZ) directions. Two variants of CP (alpha-CP and beta-CP)
      were studied and two types of carbon and phosphorous vacancies (single and
      double) were considered. It was found that carbon monovacancies have the lowest
      formation energy, while phosphorous divacancies have the highest one in both CP
      allotropes. A strong mechanical anisotropy for CP was found with the Young's
      modulus and the failure stress along ZZ direction being an order of magnitude
      larger than those along AC direction. In both allotropes, the Young's modulus,
      failure stress and strain are considerably affected by vacancies, especially
      along AC direction. Fracture of pristine CP monolayer occurred via the rupture of
      phosphorous-phosphorous bonds when CP monolayer is stretched along AC direction,
      while via the rupture of carbon-phosphorous bonds when stretched along ZZ
      direction. Defective alpha-CP and beta-CP monolayers both undergo a brittle-like
      failure initiated around the hosted vacancies at a lower critical strain. The
      failure strain and stress along the AC direction are affected only by phosphorous
      vacancies, while along the ZZ direction, they are almost equally affected by both
      phosphorous and carbon vacancies. These understandings may provide useful
      guidelines for potential applications of CP monolayers in nanoelectromechanical
      systems.

PMID- 30102244
TI  - Confined states in graphene quantum blisters.
AB  - Bilayer graphene samples may exhibit regions where the two layers are locally
      delaminated forming a so-called quantum blister in the graphene sheet. Electron
      and hole states can be confined in this graphene quantum blisters (GQB) by
      applying a global electrostatic bias. We scrutinize the electronic properties of
      these confined states under the variation of interlayer bias, coupling, and
      blister's size. The spectra display strong anti-crossings due to the coupling of
      the confined states on upper and lower layers inside the blister. These spectra
      are layer localized where the respective confined states reside on either layer
      or equally distributed. For finite angular momentum, this layer localization can
      be at the edge of the blister and corresponds to degenerate modes of opposite
      momenta. Furthermore, the energy levels in GQB exhibit electron-hole symmetry
      that is sensitive to the electrostatic bias. Finally, we demonstrate that
      confinement in GQB persists even in the presence of a variation in the inter
      layer coupling.

PMID- 30102245
TI  - Feedback and tunneling operations of a p +-i-n + silicon nanowire field-effect
      transistor.
AB  - In this paper, we describe the feedback and tunneling operations of a dual top
      gate field-effect transistor (FET) with a p +-i-n + doped silicon nanowire
      channel. The transistor functions selectively in either a feedback FET (FBFET) or
      a tunneling FET mode by modulating the source-to-drain voltage, and it features
      an outstanding subthreshold swing characteristic of 6.15 mV dec-1 with an on/off
      current ratio (I on/I off) of approximately 106 in the feedback operating mode
      and of 41.3 mV dec-1 with I on/I off of ~107 in the tunneling operating mode.
      Moreover, our device in the FBFET operation mode has memory characteristics with
      a retention time of 104 s and a program/erase endurance up to 103 cycles owing to
      the positive feedback loop in the channel region. This study demonstrates the
      promising potential of our devices in the development of multifunctional
      electronics.

PMID- 30102246
TI  - Particles in exhaled air (PExA): non-invasive phenotyping of small airways
      disease in adult asthma.
AB  - RATIONALE: Asthma is often characterised by inflammation, damage and dysfunction
      of the small airways, but no standardised biomarkers are available. OBJECTIVES:
      Using a novel approach-particles in exhaled air (PExA)-we sought to (a) sample
      and analyse abundant protein biomarkers: surfactant protein A (SPA) and albumin
      in adult asthmatic and healthy patients and (b) relate protein concentrations
      with physiological markers using phenotyping. METHODS: 83 adult asthmatics and 21
      healthy volunteers were recruited from a discovery cohort in Leicester, UK, and
      32 adult asthmatics as replication cohort from Sweden. Markers of airways
      closure/small airways dysfunction were evaluated using forced vital capacity,
      impulse oscillometry and multiple breath washout. SPA/albumin from PEx (PExA
      sample) were analysed using ELISA and corrected for acquired particle mass.
      Topological data analysis (TDA) was applied to small airway physiology and PExA
      protein data to identify phenotypes. RESULTS: PExA manoeuvres were feasible,
      including severe asthmatic subjects. TDA identified a clinically important
      phenotype of asthmatic patients with multiple physiological markers of peripheral
      airway dysfunction, and significantly lower levels of both SPA and albumin.
      CONCLUSION: We report that the PExA method is feasible across the spectrum of
      asthma severity and could be used to identify small airway disease phenotypes.

PMID- 30102247
TI  - A multi-slot coaxial microwave antenna for liver tumor ablation.
AB  - This paper presents a multi-slot coaxial antenna with a pi impedance matching
      network for liver tumor ablation. A multi-slot radiating probe was optimized by
      using the modified genetic algorithm to produce a near-spherical heating zone
      with significantly increased possibility of conformal treatment. A pi impedance
      matching network was designed to match the feeding transmission line and antenna
      without increasing antenna size. The reflection coefficient, ablation zone shape,
      specific absorption rate, and temperature were determined by a finite element
      electromagnetic simulation using COMSOL. Experimental validations were designed
      to evaluate the proposed antenna. Both simulation and experimental results show
      that the proposed antenna has the ability for liver tumor ablation, which offers
      faster heating rates in the heating center and more localized heating
      distribution than the conventional single-slot antenna.

PMID- 30102248
TI  - ECG signal classification for the detection of cardiac arrhythmias using a
      convolutional recurrent neural network.
AB  - OBJECTIVE: The electrocardiogram (ECG) provides an effective, non-invasive
      approach for clinical diagnosis in patients with cardiac diseases such as atrial
      fibrillation (AF). AF is the most common cardiac rhythm disturbance and affects
      ~2% of the general population in industrialized countries. Automatic AF detection
      in clinics remains a challenging task due to the high inter-patient variability
      of ECGs, and unsatisfactory existing approaches for AF diagnosis (e.g. atrial or
      ventricular activity-based analyses). APPROACH: We have developed RhythmNet, a 21
      layer 1D convolutional recurrent neural network, trained using 8528 single-lead
      ECG recordings from the 2017 PhysioNet/Computing in Cardiology (CinC) Challenge,
      to classify ECGs of different rhythms including AF automatically. Our RhythmNet
      architecture contained 16 convolutions to extract features directly from raw ECG
      waveforms, followed by three recurrent layers to process ECGs of varying lengths
      and to detect arrhythmia events in long recordings. Large 15  *  1 convolutional
      filters were used to effectively learn the detailed variations of the signal
      within small time-frames such as the P-waves and QRS complexes. We employed
      residual connections throughout RhythmNet, along with batch-normalization and
      rectified linear activation units to improve convergence during training. MAIN
      RESULTS: We evaluated our algorithm on 3658 testing data and obtained an F 1
      accuracy of 82% for classifying sinus rhythm, AF, and other arrhythmias.
      RhythmNet was also ranked 5th in the 2017 CinC Challenge. SIGNIFICANCE:
      Potentially, our approach could aid AF diagnosis in clinics and be used for
      patient self-monitoring to improve the early detection and effective treatment of
      AF.

PMID- 30102249
TI  - Confounding effect of benign pulmonary diseases in selecting volatile organic
      compounds as markers of lung cancer.
AB  - Lung cancer (LC) is a leading cause of cancer-related morbidity and mortality
      globally, and exhaled breath testing has been considered as a fast, convenient
      and non-invasive way to diagnose LC in its early stages. Volatile organic
      compounds (VOCs), as markers of LC in exhaled breath, have been widely
      investigated for cancer diagnosis. However, few studies have reported on the
      interference of benign pulmonary diseases (BPD) in the selection of VOC markers
      for LC. During this study, 207 samples were analyzed using thermal desorption
      instrumentation/gas chromatography/mass spectrometry (TD-GCMS) to detect C6-C30
      VOCs, and all samples were divided into four groups: LC group, BPD group, lung
      disease (LD) group (including LC group and BPD group) and healthy group. To make
      up for the deficiency of detecting low carbon hydrocarbons (<C6), 277 samples
      were analyzed using solid-phase micro-extraction/gas chromatography/mass
      spectrometry (SPME-GCMS), divided among the four groups. VOC markers were
      selected by reference to the receiver operating characteristics curve. With the
      comparisons among the LC group, BPD group and healthy group from TD-GCMS and SPME
      GCMS results, we found that exhaled VOCs are capable of discriminating LC group
      versus healthy group and BPD group versus healthy group with a consistency of 70%
      80%. However, no VOCs can be selected with good discrimination capability between
      the LC group and BPD group, indicating that BPD interferes significantly in VOC
      marker selection for LC. To discriminate breath samples from the LD group and
      healthy group, 11 VOCs, including ten selected from TD-GCMS and one from SPME
      GCMS, were chosen as markers for LD diagnosis. The sensitivity, specificity and
      overall accuracy of the diagnostic model established using ten VOCs were 80.8%,
      84% and 82.7%, and those of the model established by using one VOC were 75.6%,
      78.9% and 76.7%. These results validate that LD patients can be effectively
      discriminated and diagnosed using exhaled VOC analysis. (Clinical trial
      registration number: ChiCTR-DCD-15007106.).

PMID- 30102250
TI  - Substituting gelatine with Pluronic F-127 matrix in 3D polymer gel dosimeters can
      improve nuclear magnetic resonance, thermal and optical properties.
AB  - This work discusses the substitution of a gelatine physical gel matrix with a
      matrix made of poly(ethylene oxide)-block-poly(propylene oxide)-block
      poly(ethylene oxide) (Pluronic F-127) in five 3D radiotherapy polymer gel
      dosimeters: MAGAT, PAGAT, NIPAM, VIPARnd (VIP) and VIPARCT (VIC). The current
      research outcomes showed that not each polymer gel dosimeter could be
      manufactured with Pluronic F-127. Two of the polymer gel dosimeters (PAGAT and
      VIP) containing the Pluronic F-127 matrix allowed for some proper dose response
      for radiotherapy dosimetry (a response to a dose range of e.g. 0-50 Gy). The new
      best performing Pluronic-based polymer gel dosimeters were characterised by
      improved nuclear magnetic resonance properties, when being compared to gels with
      gelatine matrix at the same monomer content. These are: (i) a ~33% higher dose
      sensitivity; (ii) a comparable or slightly higher linear and dynamic dose range
      and (iii) a lower (new VIP composition, VIP3) or equivocal (new PAGAT
      composition, PAGAT2-Pluronic) dose threshold. However, there might be optimised
      gelatine based polymer dosimeters demonstrating even better sensitivity. UV-vis
      spectrophotometry measurements revealed that Pluronic matrices ensure six-times
      lower (VIP3-Pluronic) and eight-times lower (PAGAT2-Pluronic) absorbance (at 400
      nm) of non-irradiated gels compared to gelatine matrices, which makes the new
      polymer gel dosimeters optically improved in comparison to their corresponding
      gelatine-based compositions. The differences in absorption reduce for higher
      wavelengths. Differential scanning calorimetry measurements revealed the
      following temperature stability ranges for the gels: (i) VIP with gelatine
      matrix: 0  degrees C-26  degrees C, (ii) VIP3 with Pluronic matrix: 13.8  degrees
      C-55.2  degrees C, (iii) PAGAT2 with gelatine matrix: 0  degrees C-80  degrees C
      and (iv) PAGAT2 with Pluronic matrix: 21.4  degrees C-55.2  degrees C. In
      conclusion, Pluronic F-127 is an attractive co-polymer to serve as a substitute
      for the gelatine matrix in some 3D polymer gel dosimeters.

PMID- 30102251
TI  - Parallel use of a convolutional neural network and bagged tree ensemble for the
      classification of Holter ECG.
AB  - : The automated detection of arrhythmia in a Holter ECG signal is a challenging
      task due to its complex clinical content and data quantity. It is also
      challenging due to the fact that Holter ECG is usually affected by noise. Such
      noise may be the result of the regular activity of patients using the Holter ECG
      partially unplugged electrodes, short-time disconnections due to movement, or
      disturbances caused by electric devices or infrastructure. Furthermore, regular
      patient activities such as movement also affect the ECG signals and, in
      connection with artificial noise, may render the ECG non-readable or may lead to
      misinterpretation of the ECG. OBJECTIVE: In accordance with the PhysioNet/CinC
      Challenge 2017, we propose a method for automated classification of 1-lead Holter
      ECG recordings. APPROACH: The proposed method classifies a tested record into one
      of four classes-'normal', 'atrial fibrillation', 'other arrhythmia' or 'too noisy
      to classify'. It uses two machine learning methods in parallel. The first-a
      bagged tree ensemble (BTE)-processes a set of 43 features based on QRS detection
      and PQRS morphology. The second-a convolutional neural network connected to a
      shallow neural network (CNN/NN)-uses ECG filtered by nine different filters (8* 
      envelograms, 1*  band-pass). If the output of CNN/NN reaches a specific level of
      certainty, its output is used. Otherwise, the BTE output is preferred. MAIN
      RESULTS: The proposed method was trained using a reduced version of the public
      PhysioNet/CinC Challenge 2017 dataset (8183 records) and remotely tested on the
      hidden dataset on PhysioNet servers (3658 records). The method achieved F1 test
      scores of 0.92, 0.82 and 0.74 for normal recordings, atrial fibrillation and
      recordings containing other arrhythmias, respectively. The overall F1 score
      measured on the hidden test-set was 0.83. SIGNIFICANCE: This F1 score led to
      shared rank #2 in the follow-up PhysioNet/CinC Challenge 2017 ranking.

PMID- 30102252
TI  - Lung injury and fibrosis induced by a mutant form of surfactant protein C.
AB  - Although mutant forms of the gene encoding surfactant protein C (SFTPC) have been
      linked to interstitial lung disease, the mechanisms by which the most common of
      these mutations, SFTPCI73T, results in lung fibrosis are uncertain. In this issue
      of the JCI, Nureki et al. developed a knockin mouse model and showed that
      SFTPCI73T is expressed by alveolar type II (AT2) epithelial cells in the lungs.
      These mice developed an age-related fibrotic phenotype when the mutant allele was
      expressed at low levels and acute lung inflammation/injury followed by lung
      fibrosis when mutant SFTPCI73T expression was enhanced. This work provides
      important information regarding the impact of AT2 cell dysfunction on fibrotic
      remodeling in the lungs.

PMID- 30102253
TI  - Acute inflammation: endogenous cannabinoids mellow the harsh proinflammatory
      environment.
AB  - Under normal conditions, there is a paucity of neutrophils within the intestinal
      mucosa; however, these innate immune cells rapidly infiltrate the mucosa in
      response to infection and are critical for pathogen control. Unfortunately, these
      cells can cause extensive damage to the intestine if the initial inflammatory
      influx is not resolved. Factors that promote resolution of inflammation are of
      great interest, as they have therapeutic potential for limiting uncontrolled
      inflammatory damage. In this issue of the JCI, Szabady et al. demonstrate that
      the multidrug resistance transporter P-glycoprotein (P-gp) secretes
      endocannabinoids into the intestinal lumen that counteract the proinflammatory
      actions of the eicosanoid hepoxilin A3, which is secreted into the lumen by the
      efflux pump MRP2 and serves as a potent neutrophil chemoattractant. Moreover, the
      antiinflammatory actions of P-gp-secreted endocannabinoids were mediated by
      peripheral cannabinoid receptor CB2 on neutrophils. Together, the results of this
      study identify an important mechanism by which endogenous endocannabinoids
      facilitate the resolution of inflammation; this mechanism has potential to be
      therapeutically exploited.

PMID- 30102254
TI  - Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and
      maintain homeostasis.
AB  - Neutrophil influx into the intestinal lumen is a critical response to infectious
      agents, but is also associated with severe intestinal damage observed in
      idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an
      eicosanoid secreted from intestinal epithelial cells by the apically restricted
      efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil
      influx. Information about a possible counterbalance pathway that could signal the
      lack of or resolution of an apical inflammatory signal, however, has yet to be
      described. We now report a system with such hallmarks. Specifically, we identify
      endocannabinoids as the first known endogenous substrates of the apically
      restricted multidrug resistance transporter P-glycoprotein (P-gp) and reveal a
      mechanism, which we believe is novel, for endocannabinoid secretion into the
      intestinal lumen. Knockdown or inhibition of P-gp reduced luminal secretion
      levels of N-acyl ethanolamine-type endocannabinoids, which correlated with
      increased neutrophil transmigration in vitro and in vivo. Additionally, loss of
      CB2, the peripheral cannabinoid receptor, led to increased pathology and
      neutrophil influx in models of acute intestinal inflammation. These results
      define a key role for epithelial cells in balancing the constitutive secretion of
      antiinflammatory lipids with the stimulated secretion of proinflammatory lipids
      via surface efflux pumps in order to control neutrophil infiltration into the
      intestinal lumen and maintain homeostasis in the healthy intestine.

PMID- 30102257
TI  - The red blood cell death receptor and thrombosis.
AB  - RBCs are the most abundant circulating cells in humans and typically comprise 35%
      to 45% of the blood volume (hematocrit). Anemia is associated with an increase in
      bleeding, and epidemiological studies have shown an association between an
      elevated hematocrit and thrombosis. RBCs may contribute to hemostasis and
      thrombosis via mechanisms that include platelet margination leading to an
      increase in the near-wall platelet concentration, blood viscosity, thrombin
      generation, and platelet activation. In this issue of the JCI, Klatt et al.
      report that binding of the Fas ligand FasL on the surface of platelets to its
      cognate receptor FasR on the surface of RBCs increases thrombin generation in
      vitro and thrombosis in mouse models. This represents a new mechanism by which
      RBCs contribute to thrombosis.

PMID- 30102255
TI  - CD28 blockade controls T cell activation to prevent graft-versus-host disease in
      primates.
AB  - Controlling graft-versus-host disease (GVHD) remains a major unmet need in stem
      cell transplantation, and new, targeted therapies are being actively developed.
      CD28-CD80/86 costimulation blockade represents a promising strategy, but
      targeting CD80/CD86 with CTLA4-Ig may be associated with undesired blockade of
      coinhibitory pathways. In contrast, targeted blockade of CD28 exclusively
      inhibits T cell costimulation and may more potently prevent GVHD. Here, we
      investigated FR104, an antagonistic CD28-specific pegylated-Fab', in the nonhuman
      primate (NHP) GVHD model and completed a multiparameter interrogation comparing
      it with CTLA4-Ig, with and without sirolimus, including clinical,
      histopathologic, flow cytometric, and transcriptomic analyses. We document that
      FR104 monoprophylaxis and combined prophylaxis with FR104/sirolimus led to
      enhanced control of effector T cell proliferation and activation compared with
      the use of CTLA4-Ig or CTLA4-Ig/sirolimus. Importantly, FR104/sirolimus did not
      lead to a beneficial impact on Treg reconstitution or homeostasis, consistent
      with control of conventional T cell activation and IL-2 production needed to
      support Tregs. While FR104/sirolimus had a salutary effect on GVHD-free survival,
      overall survival was not improved, due to death in the absence of GVHD in several
      FR104/sirolimus recipients in the setting of sepsis and a paralyzed INF-gamma
      response. These results therefore suggest that effectively deploying CD28 in the
      clinic will require close scrutiny of both the benefits and risks of extensively
      abrogating conventional T cell activation after transplant.

PMID- 30102259
TI  - Academic Partnerships: Preparing Nurse Practitioners for Underserved Populations.
AB  - Medically underserved populations suffer disproportionately from disease and poor
      health, and nursing schools are challenged to prepare nurse practitioner students
      to effectively care for underserved patients. This article describes one
      university's endeavor to create and evaluate academic partnerships with
      HIV/hepatitis C virus primary care clinics in underserved settings. Designated
      preceptorships and specific preparation of students tailored for this population
      via online modules were strategies created to increase students' readiness to
      practice as primary care providers and increase clinical placements for nurse
      practitioner students. Outcomes include student readiness to practice and student
      satisfaction with clinics and preceptors.

PMID- 30102256
TI  - Epsin deficiency promotes lymphangiogenesis through regulation of VEGFR3
      degradation in diabetes.
AB  - Impaired lymphangiogenesis is a complication of chronic complex diseases,
      including diabetes. VEGF-C/VEGFR3 signaling promotes lymphangiogenesis, but how
      this pathway is affected in diabetes remains poorly understood. We previously
      demonstrated that loss of epsins 1 and 2 in lymphatic endothelial cells (LECs)
      prevented VEGF-C-induced VEGFR3 from endocytosis and degradation. Here, we report
      that diabetes attenuated VEGF-C-induced lymphangiogenesis in corneal micropocket
      and Matrigel plug assays in WT mice but not in mice with inducible lymphatic
      specific deficiency of epsins 1 and 2 (LEC-iDKO). Consistently, LECs isolated
      from diabetic LEC-iDKO mice elevated in vitro proliferation, migration, and tube
      formation in response to VEGF-C over diabetic WT mice. Mechanistically, ROS
      produced in diabetes induced c-Src-dependent but VEGF-C-independent VEGFR3
      phosphorylation, and upregulated epsins through the activation of transcription
      factor AP-1. Augmented epsins bound to and promoted degradation of newly
      synthesized VEGFR3 in the Golgi, resulting in reduced availability of VEGFR3 at
      the cell surface. Preclinically, the loss of lymphatic-specific epsins alleviated
      insufficient lymphangiogenesis and accelerated the resolution of tail edema in
      diabetic mice. Collectively, our studies indicate that inhibiting expression of
      epsins in diabetes protects VEGFR3 against degradation and ameliorates diabetes
      triggered inhibition of lymphangiogenesis, thereby providing a novel potential
      therapeutic strategy to treat diabetic complications.

PMID- 30102258
TI  - SNAP23 regulates BAX-dependent adipocyte programmed cell death independently of
      canonical macroautophagy.
AB  - The t-SNARE protein SNAP23 conventionally functions as a component of the
      cellular machinery required for intracellular transport vesicle fusion with
      target membranes and has been implicated in the regulation of fasting glucose
      levels, BMI, and type 2 diabetes. Surprisingly, we observed that adipocyte
      specific KO of SNAP23 in mice resulted in a temporal development of severe
      generalized lipodystrophy associated with adipose tissue inflammation, insulin
      resistance, hyperglycemia, liver steatosis, and early death. This resulted from
      adipocyte cell death associated with an inhibition of macroautophagy and
      lysosomal degradation of the proapoptotic regulator BAX, with increased BAX
      activation. BAX colocalized with LC3-positive autophagic vacuoles and was
      increased upon treatment with lysosome inhibitors. Moreover, BAX deficiency
      suppressed the lipodystrophic phenotype in the adipocyte-specific SNAP23-KO mice
      and prevented cell death. In addition, ATG9 deficiency phenocopied SNAP23
      deficiency, whereas ATG7 deficiency had no effect on BAX protein levels, BAX
      activation, or apoptotic cell death. These data demonstrate a role for SNAP23 in
      the control of macroautophagy and programmed cell death through an ATG9
      dependent, but ATG7-independent, pathway regulating BAX protein levels and BAX
      activation.

PMID- 30102260
TI  - Evaluation of Intraoperative Assessments in the Management of Endometrial
      Carcinoma: A Retrospective Quality Assurance Review.
AB  - Intraoperative assessment (IA) of uteri is often used to help determine whether
      to perform lymphadenectomy in patients with endometrial carcinoma. We sought to
      perform a quality assurance review of the practice of IA at our institution. In a
      1-yr period, 107 hysterectomies had an IA performed. Grade of neoplasm in
      preoperative endometrial biopsy, neoplasm size, depth of myometrial invasion at
      IA, operative management, and final histologic features were recorded. Operative
      reports were reviewed to assess the surgeon's interpretation of the IA and the
      effect on surgical management. The sensitivity and specificity for IA of deep
      myometrial invasion (>50% myometrial thickness) compared with final histology was
      76.9% and 91.1%. The positive predictive value was 71.4%, negative predictive
      value 93.2% and accuracy 88%. Neoplasm size was provided in 47% of cases. In 10%
      of patients lymphadenectomy was performed despite low-risk features. IA results
      were included in the operative report in 87% of cases. There were differences in
      8.4% of cases between the IA diagnosis and the surgeon's operative report. IA of
      deep myometrial invasion is reliable at our institution. Several metrics for
      quality improvement have been identified as a result of this retrospective
      review. These include but are not limited to more reliable reporting of neoplasm
      size, documentation, and communication with gynecologic oncologists.

PMID- 30102261
TI  - Nonadherence to National Guidelines for Antibiotic Treatment of Uncomplicated
      Gonorrhea in China: Results From a Nationwide Survey.
AB  - BACKGROUND: Provider adherence to the national treatment guidelines for gonorrhea
      is critical to assuring effective treatment. It is also an important means of
      limiting antibiotic overuse, which can lead to development of resistant bacteria.
      The Chinese treatment guidelines recommend the monotherapy with ceftriaxone or
      spectinomycin in accordance with the World Health Organization guidelines for
      treatment of uncomplicated gonorrhea. We evaluated adherence to the guidelines
      among treatment providers in China. METHODS: The study was a nationwide cross
      sectional study. In each of the 6 geographic regions in China, at least 1
      province was selected. In each selected province, cities with elevated incidence
      of reported gonorrhea were purposively selected. Using a questionnaire, 2121
      physicians recruited from 512 different categories and levels of health sectors
      from July to September 2017 were investigated. RESULTS: Of the participants, more
      than 99% diagnosed gonorrhea using one of the laboratory tests including Gram
      stain, culture, nucleic acid amplification test, or other tests. Culture was the
      predominant assay of the choice for the diagnosis. Of the 1890 physicians who
      provided information on prescription behaviors, 62.2% were not adherent to the
      regimens for treatment of uncomplicated gonorrhea recommended by the National
      Sexually Transmitted Disease (STD) Treatment Guidelines (National STD
      Guidelines). Physicians working in the areas located in Northern China (adjusted
      odds ratio [AOR], 3.06; 95% confidence intervals [CIs], 1.77-5.31), in general
      hospitals or departments of urology (AOR, 1.54; 95% CIs, 1.08-2.19), diagnosing
      more cases in the past 6 months (AOR, 1.82; 95% CIs, 1.25-2.67), or unfamiliar
      with the treatment regimens in the National STD Guidelines (AOR, 3.48; 95% CIs,
      2.76-4.37) were significantly more likely to be nonadherent to the National STD
      Guidelines. CONCLUSIONS: It can be concluded from our study that nonadherence to
      the national guidelines and empirical treatment with high doses of ceftriaxone
      occurred frequently in China. Further studies on the impacts of the empirical
      treatment on antimicrobial resistance of gonorrhea are needed.

PMID- 30102262
TI  - Body Parts Matter: Social, Behavioral, and Biological Considerations for
      Urethral, Pharyngeal, and Rectal Gonorrhea and Chlamydia Screening Among MSM in
      Lima, Peru.
AB  - BACKGROUND: Gonorrhea (Neisseria gonorrhoeae [GC]) and chlamydia (Chlamydia
      trachomatis [CT]) disproportionately affect men who have sex with men (MSM), and
      public health implications vary by anatomic site and bacterial agent. Urethral
      and rectal GC and CT can increase risk of HIV transmission, whereas pharyngeal GC
      may be a reservoir for antimicrobial resistance. To define screening priorities
      in Latin America, we compare differences in the prevalence and correlates of
      urethral, pharyngeal, and rectal GC and CT among MSM in Peru. METHODS: A cross
      sectional sample of 787 MSM from Lima was screened between 2012 and 2014. We
      described prevalence of urethral, pharyngeal, and rectal GC and CT infection and
      conducted bivariate analyses of associations with social, behavioral, and
      biological characteristics. Poisson regression analyses assessed the correlates
      of each infection at each anatomic site. RESULTS: The most commonly symptomatic
      infection (urethral GC; 42.1%) was the least prevalent (2.4%). The most prevalent
      infections were rectal CT (15.8%) and pharyngeal GC (9.9%). Rectal CT was the
      least commonly symptomatic (2.4%) infection, and was associated with younger age
      (adjusted prevalence ratio [95% confidence interval], 0.96 [0.94-0.98]), HIV
      infection (1.46 [1.06-2.02]), and pasivo (receptive; 3.59 [1.62-7.95]) and
      moderno (versatile; 2.63 [1.23-5.60]) sexual roles. CONCLUSIONS: Results
      highlight limitations of current syndromic screening strategies for sexually
      transmitted diseases in Peru, wherein urethral CT and rectal GC and CT may be
      missed due to their frequently asymptomatic presentations. Successful management
      of GC and CT infections among MSM in low-resource settings requires
      differentiating between bacterial agent, symptomatic presentation, associated
      risk factors, and public health implications of untreated infection at different
      anatomic sites.

PMID- 30102263
TI  - Isolation and Analysis of Microbial Communities in Soil, Rhizosphere, and Roots
      in Perennial Grass Experiments.
AB  - Plant and soil microbiome studies are becoming increasingly important for
      understanding the roles microorganisms play in agricultural productivity. The
      purpose of this manuscript is to provide detail on how to rapidly sample soil,
      rhizosphere, and endosphere of replicated field trials and analyze changes that
      may occur in the microbial communities due to sample type, treatment, and plant
      genotype. The experiment used to demonstrate these methods consists of replicated
      field plots containing two, pure, warm-season grasses (Panicum virgatum and
      Andropogon gerardii) and a low-diversity grass mixture (A. gerardii, Sorghastrum
      nutans, and Bouteloua curtipendula). Briefly, plants are excavated, a variety of
      roots are cut and placed in phosphate buffer, and then shaken to collect the
      rhizosphere. Roots are brought to the laboratory on ice and surface sterilized
      with bleach and ethanol (EtOH). The rhizosphere is filtered and concentrated by
      centrifugation. Excavated soil from around the root ball is placed into plastic
      bags and brought to the lab where a small amount of soil is taken for DNA
      extractions. DNA is extracted from roots, soil, and rhizosphere and then
      amplified with primers for the V4 region of the 16S rRNA gene. Amplicons are
      sequenced, then analyzed with open access bioinformatics tools. These methods
      allow researchers to test how the microbial community diversity and composition
      varies due to sample type, treatment, and plant genotype. Using these methods
      along with statistical models, the representative results demonstrate there are
      significant differences in microbial communities of roots, rhizosphere, and soil.
      Methods presented here provide a complete set of steps for how to collect field
      samples, isolate, extract, quantify, amplify, and sequence DNA, and analyze
      microbial community diversity and composition in replicated field trials.

PMID- 30102264
TI  - Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related
      Heart Failure with Preserved Ejection Fraction.
AB  - In this article, we describe an optimized, Langendorff-based procedure for the
      isolation of single-cell atrial cardiomyocytes (ACMs) from a rat model of
      metabolic syndrome (MetS)-related heart failure with preserved ejection fraction
      (HFpEF). The prevalence of MetS-related HFpEF is rising, and atrial
      cardiomyopathies associated with atrial remodeling and atrial fibrillation are
      clinically highly relevant as atrial remodeling is an independent predictor of
      mortality. Studies with isolated single-cell cardiomyocytes are frequently used
      to corroborate and complement in vivo findings. Circulatory vessel rarefication
      and interstitial tissue fibrosis pose a potentially limiting factor for the
      successful single-cell isolation of ACMs from animal models of this disease. We
      have addressed this issue by employing a device capable of manually regulating
      the intraluminal pressure of cardiac cavities during the isolation procedure,
      substantially increasing the yield of morphologically and functionally intact
      ACMs. The acquired cells can be used in a variety of different experiments, such
      as cell culture and functional Calcium imaging (i.e., excitation-contraction
      coupling). We provide the researcher with a step-by-step protocol, a list of
      optimized solutions, thorough instructions to prepare the necessary equipment,
      and a comprehensive troubleshooting guide. While the initial implementation of
      the procedure might be rather difficult, a successful adaptation will allow the
      reader to perform state-of-the-art ACM isolations in a rat model of MetS-related
      HFpEF for a broad spectrum of experiments.

PMID- 30102265
TI  - Application of Elemental Lanthanides in the Selective C-F Activation of
      Trifluoromethylated Benzofulvenes Providing Access to Various Difluoroalkenes.
AB  - The selective activation of one carbon-fluorine bond in polyfluorinated aromatic
      molecules or in trifluoromethyl-containing substrates offers the possibility of
      accessing unique fluorine-containing molecules, which are difficult to obtain by
      other synthetic pathways. Among various metals, which can undergo C-F activation,
      lanthanides (Ln) are good candidates as they form strong Ln-F bonds. Lanthanide
      metals are strong reducing agents with a redox potential Ln3+/Ln of approximately
      -2.3 V, which is comparable to the value of the Mg2+/Mg redox couple. In
      addition, lanthanide metals display a promising functional group tolerance and
      their reactivity can vary along the lanthanide series, making them suitable
      reagents for fine-tuning reaction conditions in organic and organometallic
      transformations. However, due to their oxophilicity, lanthanides react readily
      with oxygen and water and therefore require special conditions for storage,
      handling, preparation, and activation. These factors have limited a more
      widespread use in organic synthesis. We herein present how dysprosium metal - and
      by analogy all lanthanide metals - can be freshly prepared under anhydrous
      conditions using glovebox and Schlenk techniques. The freshly filed metal, in
      combination with aluminum chloride, initiates the selective C-F activation in
      trifluoromethylated benzofulvenes. The resulting reaction intermediates react
      with nitroalkenes to obtain a new family of difluoroalkenes.

PMID- 30102266
TI  - Live Cell Imaging of the TGF- beta/Smad3 Signaling Pathway In Vitro and In Vivo
      Using an Adenovirus Reporter System.
AB  - Transforming Growth Factor beta (TGF-beta) signaling regulates many important
      functions required for cellular homeostasis and is commonly found overexpressed
      in many diseases, including cancer. TGF-beta is strongly implicated in metastasis
      during late stage cancer progression, activating a subset of migratory and
      invasive tumor cells. Current methods for signaling pathway analysis focus on
      endpoint models, which often attempt to measure signaling post-hoc of the
      biological event and do not reflect the progressive nature of the disease. Here,
      we demonstrate a novel adenovirus reporter system specific for the TGF-beta/Smad3
      signaling pathway that can detect transcriptional activation in live cells.
      Utilizing an Ad-CAGA12-Td-Tom reporter, we can achieve a 100% infection rate of
      MDA-MB-231 cells within 24 h in vitro. The use of a fluorescent reporter allows
      for imaging of live single cells in real-time with direct identification of
      transcriptionally active cells. Stimulation of infected cells with TGF-beta
      displays only a subset of cells that are transcriptionally active and involved in
      specific biological functions. This approach allows for high specificity and
      sensitivity at a single cell level to enhance understanding of biological
      functions related to TGF-beta signaling in vitro. Smad3 transcriptional activity
      can also be reported in vivo in real-time through the application of an Ad-CAGA12
      Luc reporter. Ad-CAGA12-Luc can be measured in the same manner as traditional
      stably transfected luciferase cell lines. Smad3 transcriptional activity of cells
      implanted in vivo can be analyzed through conventional IVIS imaging and monitored
      live during tumor progression, providing unique insight into the dynamics of the
      TGF-beta signaling pathway. Our protocol describes an advantageous reporter
      delivery system allowing for quick high-throughput imaging of live cell signaling
      pathways both in vitro and in vivo. This method can be expanded to a range of
      image based assays and presents as a sensitive and reproducible approach for both
      basic biology and therapeutic development.

PMID- 30102267
TI  - Detecting Protein Subcellular Localization by Green Fluorescence Protein Tagging
      and 4',6-Diamidino-2-phenylindole Staining in Caenorhabditis elegans.
AB  - In this protocol, a green fluorescence protein (GFP) fusion protein and 4',6
      diamidino-2-phenylindole (DAPI) staining are used to track protein subcellular
      localization changes; in particular, a nuclear translocation under a heat stress
      condition. Proteins react correspondingly to external and internal signals. A
      common mechanism is to change its subcellular localization. This article
      describes a protocol to track protein localization that does not require an
      antibody, radioactive labeling, or a confocal microscope. In this article, GFP is
      used to tag the target protein EXL-1 in C. elegans, a member of the chloride
      intracellular channel proteins (CLICs) family, including mammalian CLIC4. An
      integrated translational exl-1::gfp transgenic line (with a promoter and a full
      gene sequence) was created by transformation and gamma-radiation, and stably
      expresses the gene and gfp. Recent research showed that upon heat stress, not
      oxidative stress, EXL-1::GFP accumulates in the nucleus. Overlapping the GFP
      signal with both the nuclei structure and the DAPI signals confirms the EXL-1
      subcellular localization changes under stress. This protocol presents two
      different fixation methods for DAPI staining: ethanol fixation and acetone
      fixation. The DAPI staining protocol presented in this article is fast and
      efficient and preserves both the GFP signal and the protein subcellular
      localization changes. This method only requires a fluorescence microscope with
      Nomarski, a FITC filter, and a DAPI filter. It is suitable for a small laboratory
      setting, undergraduate student research, high school student research, and
      biotechnology classrooms.

PMID- 30102268
TI  - Experimental Protocol for Examining Behavioral Response Profiles in Larval Fish:
      Application to the Neuro-stimulant Caffeine.
AB  - Fish models and behaviors are increasingly used in the biomedical sciences;
      however, fish have long been the subject of ecological, physiological and
      toxicological studies. Using automated digital tracking platforms, recent efforts
      in neuropharmacology are leveraging larval fish locomotor behaviors to identify
      potential therapeutic targets for novel small molecules. Similar to these
      efforts, research in the environmental sciences and comparative pharmacology and
      toxicology is examining various behaviors of fish models as diagnostic tools in
      tiered evaluation of contaminants and real-time monitoring of surface waters for
      contaminant threats. Whereas the zebrafish is a popular larval fish model in the
      biomedical sciences, the fathead minnow is a common larval fish model in
      ecotoxicology. Unfortunately, fathead minnow larvae have received considerably
      less attention in behavioral studies. Here, we develop and demonstrate a
      behavioral profile protocol using caffeine as a model neurostimulant. Though
      photomotor responses of fathead minnows were occasionally affected by caffeine,
      zebrafish were markedly more sensitive for photomotor and locomotor endpoints,
      which responded at environmentally relevant levels. Future studies are needed to
      understand comparative behavioral sensitivity differences among fish with age and
      time of day, and to determine whether similar behavioral effects would occur in
      nature and be indicative of adverse outcomes at the individual or population
      levels of biological organization.

PMID- 30102269
TI  - Decellularization and Recellularization Methodology for Human Saphenous Veins.
AB  - Vascular conduits used during most vascular surgeries are allogeneic or synthetic
      grafts that often lead to complications caused by immunosuppression and poor
      patency. Tissue engineering offers a novel solution to generate personalized
      grafts with a natural extracellular matrix containing the recipient's cells using
      the method of decellularization and recellularization. We show a detailed method
      for performing decellularization of the human saphenous vein and
      recellularization by perfusion of peripheral blood. The vein was decellularized
      by perfusing 1% Triton X-100, 1% tri-n-butyl-phosphate (TnBP) and 2,000 Kunitz
      units of deoxyribonuclease (DNase). Triton X-100 and TnBP were perfused at 35
      mL/min for 4 h while DNase was perfused at 10 mL/min at 37  degrees C for 4 h.
      The vein was washed in ultrapure water and PBS and then sterilized in 0.1%
      peracetic acid. It was washed again in PBS and preconditioned in endothelial
      medium. The vein was connected to a bioreactor and perfused with endothelial
      medium containing 50 IU/mL heparin for 1 h. Recellularization was performed by
      filling the bioreactor with fresh blood, diluted 1:1 in Steen solution, and
      adding endocrine gland-derived vascular endothelial growth factors (80 ng/mL),
      basic fibroblast growth factors (4 uL/mL), and acetyl salicylic acid (5 ug/mL).
      The bioreactor was then moved into an incubator and perfused for 48 h at 2 mL/min
      while maintaining glucose between 3 - 9 mmol/L. Later, the vein was washed with
      PBS, filled with endothelial medium and perfused for 96 h in the incubator.
      Treatment with Triton X-100, TnBP and DNase decellularized the saphenous vein in
      5 cycles. The decellularized vein looked white in contrast to normal and
      recellularized veins (light red). The hematoxylin & eosin (H&E) staining showed
      the presence of nuclei only in normal but not in decellularized veins. In the
      recellularized vein, H&E-staining showed the presence of cells on the luminal
      surface of the vein.

PMID- 30102270
TI  - Establishment of a Valuable Mimic of Alzheimer's Disease in Rat Animal Model by
      Intracerebroventricular Injection of Composited Amyloid Beta Protein.
AB  - Alzheimer's disease (AD) is an irreversible, progressive brain disease that
      slowly destroys memory and is accompanied by neuron loss and structure change.
      With the increase of AD patients worldwide, the pathology and treatment of the
      disease has become a focus in the International Pharmaceutical Industry. Thus,
      the establishment of the animal model to mimic AD in the laboratory is of great
      importance. Here, we describe a detailed protocol for establishing a mimic of AD
      in a rat animal model though intracerebroventricular injection of amyloid beta
      protein 25-35 (Abeta25-35) combined with aluminum trichloride (AlCl3) and
      anterodorsal thalamic nucleus injection of recombinant human transforming growth
      factor-beta1 (RHTGF-beta1) to rats. The related markers of AD were measured,
      including: spatial memory, neuronal structure and substructure, neuronal Abeta,
      and neurofibrillary tangles (NFT) production. This rat model demonstrates spatial
      memory impairment, neuronal structure and substructure pathological changes,
      neuron intracellular Abeta burden, and NFT aggregation, and provides a close
      mimic of the neuronal structure and function disorder to that of clinical AD
      patients. Thus, the presented AD rat modelprovides a valuable in vivo tool for
      exploring neuronal function, neuronal pathology, and drug screening of AD.

PMID- 30102271
TI  - Miniaturized Sample Preparation for Transmission Electron Microscopy.
AB  - Due to recent technological progress, cryo-electron microscopy (cryo-EM) is
      rapidly becoming a standard method for the structural analysis of protein
      complexes to atomic resolution. However, protein isolation techniques and sample
      preparation methods for EM remain a bottleneck. A relatively small number
      (100,000 to a few million) of individual protein particles need to be imaged for
      the high-resolution analysis of proteins by the single particle EM approach,
      making miniaturized sample handling techniques and microfluidic principles
      feasible. A miniaturized, paper-blotting-free EM grid preparation method for
      sample pre-conditioning, EM grid priming and post processing that only consumes
      nanoliter-volumes of sample is presented. The method uses a dispensing system
      with sub-nanoliter precision to control liquid uptake and EM grid priming, a
      platform to control the grid temperature thereby determining the relative
      humidity above the EM grid, and a pick-and-plunge-mechanism for sample
      vitrification. For cryo-EM, an EM grid is placed on the temperature-controlled
      stage and the sample is aspirated into a capillary. The capillary tip is
      positioned in proximity to the grid surface, the grid is loaded with the sample
      and excess is re-aspirated into the microcapillary. Subsequently, the sample film
      is stabilized and slightly thinned by controlled water evaporation regulated by
      the offset of the platform temperature relative to the dew-point. At a given
      point the pick-and-plunge mechanism is triggered, rapidly transferring the primed
      EM grid into liquid ethane for sample vitrification. Alternatively, sample
      conditioning methods are available to prepare nanoliter-sized sample volumes for
      negative stain (NS) EM. The methodologies greatly reduce sample consumption and
      avoid approaches potentially harmful to proteins, such as the filter paper
      blotting used in conventional methods. Furthermore, the minuscule amount of
      sample required allows novel experimental strategies, such as fast sample
      conditioning, combination with single-cell lysis for "visual proteomics," or
      "lossless" total sample preparation for quantitative analysis of complex samples.

PMID- 30102272
TI  - Bedside Ultrasound for Guiding Fluid Removal in Patients with Pulmonary Edema:
      The Reverse-FALLS Protocol.
AB  - Fluid retention is the most common risk factor for mortality and cardiovascular
      complications in patients with volume-overloaded disease states. The extent of
      diuresis or fluid removal is frequently determined by physical examination which
      is subject to inaccuracies. Bedside ultrasound (US) is a portable tool that
      brings real-time diagnostic imaging to the patient's bedside. This versatile
      modality makes it possible for the clinician to investigate patients'
      extravascular and intravascular volume states. The extravascular volume,
      particularly in the case of pulmonary edema, can be quantitatively assessed by US
      of the anterior chest. Intravascular volume is estimated by visualizing the
      inferior vena cava (IVC) caliber. Taken together, the degree of extravascular
      lung water and the IVC caliber provide objective data that can guide the
      clinician to determine the level of diuresis needed to effectively yet safely
      treat pulmonary edema. The objective of this article is threefold: 1) to
      summarize the findings of previous studies on the efficacy of portable US to
      guide fluid management, 2) to describe a proposed ultrasound protocol to help
      guide fluid management, and 3) to elucidate techniques that address the
      measurement of intravascular and extravascular volumes using portable US.

PMID- 30102274
TI  - An Efficient Sample Preparation Method to Enhance Carbohydrate Ion Signals in
      Matrix-assisted Laser Desorption/Ionization Mass Spectrometry.
AB  - Sample preparation is a critical process in mass spectrometry (MS) analysis of
      carbohydrates. Although matrix-assisted laser desorption/ionization (MALDI) MS is
      the method of choice in carbohydrate analysis, poor ion signal and data
      reproducibility of carbohydrate samples continue to be severe problems. For
      quantitative analysis of carbohydrates, an effective analytical protocol
      providing superior data quality is necessary. This video demonstrates sample
      preparation protocols to improve signal intensity and minimize data variation of
      carbohydrates in MALDI-MS. After drying and crystallization of sample droplets,
      the crystal morphology is reformed by methanol before mass spectrometric
      analysis. The enhancement in carbohydrate signal is examined with MALDI imaging
      mass spectrometry (IMS). Experimental results show that crystal reformation
      adjusts crystalline structures and redistributes carbohydrate analytes. In
      comparison with the dried droplet preparation method in conventional MALDI-MS,
      reforming carbohydrate crystal morphologies with methanol shows significantly
      better signal intensity, ion image distribution, and data stability. Since the
      protocols demonstrated herein do not involve changes in sample composition, they
      are generally applicable to various carbohydrates and matrixes.

PMID- 30102273
TI  - Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol
      Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides.
AB  - Disaccharide nucleosides, which consist of disaccharide and nucleobase moieties,
      have been known as a valuable group of natural products having multifarious
      bioactivities. Although chemical O-glycosylation is a commonly beneficial
      strategy to synthesize disaccharide nucleosides, the preparation of substrates
      such as glycosyl donors and acceptors requires tedious protecting group
      manipulations and a purification at each synthetic step. Meanwhile, several
      research groups have reported that boronic and borinic esters serve as a
      protecting or activating group of carbohydrate derivatives to achieve the regio-
      and/or stereoselective acylation, alkylation, silylation, and glycosylation. In
      this article, we demonstrate the procedure for the regioselective O-glycosylation
      of unprotected ribonucleosides utilizing boronic acid. The esterification of
      2',3'-diol of ribonucleosides with boronic acid makes the temporary protection of
      diol, and, following O-glycosylation with a glycosyl donor in the presence of p
      toluenesulfenyl chloride and silver triflate, permits the regioselective reaction
      of the 5'-hydroxyl group to afford the disaccharide nucleosides. This method
      could be applied to various nucleosides, such as guanosine, adenosine, cytidine,
      uridine, 5-metyluridine, and 5-fluorouridine. This article and the accompanying
      video represent useful (visual) information for the O-glycosylation of
      unprotected nucleosides and their analogs for the synthesis of not only
      disaccharide nucleosides, but also a variety of biologically relevant
      derivatives.

PMID- 30102275
TI  - Self-standing Electrochemical Set-up to Enrich Anode-respiring Bacteria On-site.
AB  - Anaerobic respiration coupled with electron transport to insoluble minerals
      (referred to as extracellular electron transport [EET]) is thought to be critical
      for microbial energy production and persistence in many subsurface environments,
      especially those lacking soluble terminal electron acceptors. While EET-capable
      microbes have been successfully isolated from various environments, the diversity
      of bacteria capable of EET is still poorly understood, especially in difficult-to
      sample, low energy or extreme environments, such as many subsurface ecosystems.
      Here, we describe an on-site electrochemical system to enrich EET-capable
      bacteria using an anode as a respiratory terminal electron acceptor. This anode
      is connected to a cathode capable of catalyzing abiotic oxygen reduction.
      Comparing this approach with electrocultivation methods that use a potentiostat
      for poising the electrode potential, the two-electrode system does not require an
      external power source. We present an example of our on-site enrichment utilized
      in an alkaline pond at the Cedars, a terrestrial serpentinization site in
      Northern California. Prior attempts to cultivate mineral reducing bacteria were
      unsuccessful, which is likely due to the low-biomass nature of this site and/or
      the low relative abundance of metal reducing microbes. Prior to implementing our
      two-electrode enrichment, we measured the vertical profile of dissolved oxygen
      concentration. This allowed us to place the carbon felt anode and platinum
      electroplated carbon felt cathode at depths that would support anaerobic and
      aerobic processes, respectively. Following on-site incubation, we further
      enriched the anodic electrode in the laboratory and confirmed a distinct
      microbial community compared to the surface-attached or biofilm communities
      normally observed at the Cedars. This enrichment subsequently led to the
      isolation of the first electrogenic microbe from the Cedars. This method of on
      site microbial enrichment has the potential to greatly enhance the isolation of
      EET-capable bacteria from low biomass or difficult to sample habitats.

PMID- 30102276
TI  - Combining Analysis of DNA in a Crude Virion Extraction with the Analysis of RNA
      from Infected Leaves to Discover New Virus Genomes.
AB  - This metagenome approach is used to identify plant viruses with circular DNA
      genomes and their transcripts. Often plant DNA viruses that occur in low titers
      in their host or cannot be mechanically inoculated to another host are difficult
      to propagate to achieve a greater titer of infectious material. Infected leaves
      are ground in a mild buffer with optimal pH and ionic composition recommended for
      purifying most bacilliform Para retroviruses. Urea is used to break up inclusion
      bodies that trap virions and to dissolve cellular components. Differential
      centrifugation provides further separation of virions from plant contaminants.
      Then proteinase K treatment removes the capsids. Then the viral DNA is
      concentrated and used for next-generation sequencing (NGS). The NGS data are used
      to assemble contigs which are submitted to NCBI-BLASTn to identify a subset of
      virus sequences in the generated dataset. In a parallel pipeline, RNA is isolated
      from infected leaves using a standard column-based RNA extraction method. Then
      ribosome depletion is carried out to enrich for a subset of mRNA and virus
      transcripts. Assembled sequences derived from RNA sequencing (RNA-seq) were
      submitted to NCBI-BLASTn to identify a subset of virus sequences in this dataset.
      In our study, we identified two related full-length badnavirus genomes in the two
      datasets. This method is preferred to another common approach which extracts the
      aggregate population of small RNA sequences to reconstitute plant virus genomic
      sequences. This latter metagenomic pipeline recovers virus related sequences that
      are retro-transcribing elements inserted into the plant genome. This is coupled
      to biochemical or molecular assays to further discern the actively infectious
      agents. The approach documented in this study, recovers sequences representative
      of replicating viruses that likely indicate active virus infection.

PMID- 30102277
TI  - Methodology for Establishing a Community-Wide Life Laboratory for Capturing
      Unobtrusive and Continuous Remote Activity and Health Data.
AB  - An end-to-end suite of technologies has been established for the unobtrusive and
      continuous monitoring of health and activity changes occurring in the daily life
      of older adults over extended periods of time. The technology is aggregated into
      a system that incorporates the principles of being minimally obtrusive, while
      generating secure, privacy protected, continuous objective data in real-world
      (home-based) settings for months to years. The system includes passive infrared
      presence sensors placed throughout the home, door contact sensors installed on
      exterior doors, connected physiological monitoring devices (such as scales),
      medication boxes, and wearable actigraphs. Driving sensors are also installed in
      participants' cars and computer (PC, tablet or smartphone) use is tracked. Data
      is annotated via frequent online self-report options that provide vital
      information with regard to the data that is difficult to infer via sensors such
      as internal states (e.g., pain, mood, loneliness), as well as data referent to
      activity pattern interpretation (e.g., visitors, rearranged furniture).
      Algorithms have been developed using the data obtained to identify functional
      domains key to health or disease activity monitoring, including mobility (e.g.,
      room transitions, steps, gait speed), physiologic function (e.g., weight, body
      mass index, pulse), sleep behaviors (e.g., sleep time, trips to the bathroom at
      night), medication adherence (e.g., missed doses), social engagement (e.g., time
      spent out of home, time couples spend together), and cognitive function (e.g.,
      time on computer, mouse movements, characteristics of online form completion,
      driving ability). Change detection of these functions provides a sensitive marker
      for the application in health surveillance of acute illnesses (e.g., viral
      epidemic) to the early detection of prodromal dementia syndromes. The system is
      particularly suitable for monitoring the efficacy of clinical interventions in
      natural history studies of geriatric syndromes and in clinical trials.

PMID- 30102279
TI  - Force System with Vertical V-Bends: A 3D In Vitro Assessment of Elastic and Rigid
      Rectangular Archwires.
AB  - A proper understanding of the force system created by various orthodontic
      appliances can make treatment of patients efficient and predictable. Reducing the
      complicated multi-bracket appliances to a simple two-bracket system for the
      purpose of force system evaluation will be the first step in this direction.
      However, much of the orthodontic biomechanics in this regard is confined to 2D
      experimental studies, computer modeling/analysis or theoretical extrapolation of
      existing models. The objective of this protocol is to design, construct and
      validate an in vitro 3D model capable of measuring the forces and moments
      generated by an archwire with a V-bend placed between two brackets. Additional
      objectives are to compare the force system generated by different types of
      archwires among themselves and to previous models. For this purpose, a 2 x 4
      appliance representing a molar and an incisor has been simulated. An orthodontic
      wire tester (OWT) is constructed consisting of two multi-axis force transducers
      or load cells (nanosensors) to which the orthodontic brackets are attached. The
      load cells are capable of measuring the force system in all the three planes of
      space. Two types of archwires, stainless-steel and beta-titanium of three
      different sizes (0.016 x 0.022 inch, 0.017 x 0.025 inch and 0.019 x 0.025 inch),
      are tested. Each wire receives a single vertical V-bend systematically placed at
      a specific position with a predefined angle. Similar V-bends are replicated on
      different archwires at 11 different locations between the molar and incisor
      attachments. This is the first time an attempt has been made in vitro to simulate
      an orthodontic appliance utilizing V-bends on different archwires.

PMID- 30102278
TI  - Fish Sperm Assessment Using Software and Cooling Devices.
AB  - For gamete quality evaluation, there are innovative, rapid, and quantitative
      techniques that can provide useful data for aquaculture. Computerized systems for
      sperm analysis were developed to measure several parameters and one of the most
      commonly measured is the sperm motility. Initially, this computer technology was
      designed for mammalian species, although it can also be used for fish sperm
      analysis. Fish have specific features that can affect sperm assessment such as a
      short motility time after activation and, in some cases, adaptation to lower
      temperatures. Thus, it is necessary to modify both software and hardware
      components to make motility analysis more efficient for fish sperm analysis. For
      mammalian sperm, the heating plate is used to maintain optimal temperatures of
      spermatozoa. However, for some fish species, it is advantageous to use a lower
      temperature to prolong the duration of motility, since the sperm remain active
      for less than 2 min. Therefore, cooling devices are necessary to refrigerate
      samples at constant temperature over the time of analysis, including on the
      optical microscope. This protocol describes the analysis of fish sperm motility
      using software for sperm analysis and new cooling devices to optimize the
      results.

PMID- 30102280
TI  - The Lactate Dehydrogenase Sequestration Assay - A Simple and Reliable Method to
      Determine Bulk Autophagic Sequestration Activity in Mammalian Cells.
AB  - Bulk autophagy is characterized by the sequestration of large portions of
      cytoplasm into double/multi-membrane structures termed autophagosomes. Here a
      simple protocol to monitor this process is described. Moreover, typical results
      and experimental validation of the method under autophagy-inducing conditions in
      various types of cultured mammalian cells are provided. During bulk autophagy,
      autophagosomes sequester cytosol, and thereby also soluble cytosolic proteins,
      alongside other autophagic cargo. LDH is a stable and highly abundant, soluble
      cytosolic enzyme that is non-selectively sequestered into autophagosomes. The
      amount of LDH sequestration therefore reflects the amount of bulk autophagic
      sequestration. To efficiently and accurately determine LDH sequestration in
      cells, we employ an electrodisruption-based fractionation protocol that
      effectively separates sedimentable from cytosolic LDH, followed by measurement of
      enzymatic activity in sedimentable fractions versus whole-cell samples.
      Autophagic sequestration is determined by subtracting the proportion of
      sedimentable LDH in untreated cells from that in treated cells. The advantage of
      the LDH sequestration assay is that it gives a quantitative measure of the
      autophagic sequestration of endogenous cargo, as opposed to other methods that
      either involve ectopic expression of sequestration probes or semi-quantitative
      protease protection analyses of autophagy markers or receptors.

PMID- 30102281
TI  - Sampling, Sorting, and Characterizing Microplastics in Aquatic Environments with
      High Suspended Sediment Loads and Large Floating Debris.
AB  - The ubiquitous presence of plastic debris in the ocean is widely recognized by
      the public, scientific communities, and government agencies. However, only
      recently have microplastics in freshwater systems, such as rivers and lakes, been
      quantified. Microplastic sampling at the surface usually consists of deploying
      drift nets behind either a stationary or moving boat, which limits the sampling
      to environments with low levels of suspended sediments and floating or submerged
      debris. Previous studies that employed drift nets to collect microplastic debris
      typically used nets with >=300 um mesh size, allowing plastic debris (particles
      and fibers) below this size to pass through the net and elude quantification. The
      protocol detailed here enables: 1) sample collection in environments with high
      suspended loads and floating or submerged debris and 2) the capture and
      quantification of microplastic particles and fibers <300 um. Water samples were
      collected using a peristaltic pump in low-density polyethylene (PE) containers to
      be stored before filtering and analysis in the lab. Filtration was done with a
      custom-made microplastic filtration device containing detachable union joints
      that housed nylon mesh sieves and mixed cellulose ester membrane filters. Mesh
      sieves and membrane filters were examined with a stereomicroscope to quantify and
      separate microplastic particulates and fibers. These materials were then examined
      using a micro-attenuated total reflectance Fourier transform infrared
      spectrometer (micro ATR-FTIR) to determine microplastic polymer type. Recovery
      was measured by spiking samples using blue PE particulates and green nylon
      fibers; percent recovery was determined to be 100% for particulates and 92% for
      fibers. This protocol will guide similar studies on microplastics in high
      velocity rivers with high concentrations of sediment. With simple modifications
      to the peristaltic pump and filtration device, users can collect and analyze
      various sample volumes and particulate sizes.

PMID- 30102282
TI  - A Direct Force Probe for Measuring Mechanical Integration Between the Nucleus and
      the Cytoskeleton.
AB  - The mechanical properties of the nucleus determine its response to mechanical
      forces generated in cells. Because the nucleus is molecularly continuous with the
      cytoskeleton, methods are needed to probe its mechanical behavior in adherent
      cells. Here, we discuss the direct force probe (DFP) as a tool to apply force
      directly to the nucleus in a living adherent cell. We attach a narrow
      micropipette to the nuclear surface with suction. The micropipette is translated
      away from the nucleus, which causes the nucleus to deform and translate. When the
      restoring force is equal to the suction force, the nucleus detaches and
      elastically relaxes. Because the suction pressure is precisely known, the force
      on the nuclear surface is known. This method has revealed that nano-scale forces
      are sufficient to deform and translate the nucleus in adherent cells, and
      identified cytoskeletal elements that enable the nucleus to resist forces. The
      DFP can be used to dissect the contributions of cellular and nuclear components
      to nuclear mechanical properties in living cells.

PMID- 30102283
TI  - Semi-automated Production of Hepatocyte Like Cells from Pluripotent Stem Cells.
AB  - Human pluripotent stem cells represent a renewable source of human tissue. Our
      research is focused on generating human liver tissue from human embryonic stem
      cells (hESCs) and induced pluripotent stem cells (iPSCs). Current differentiation
      procedures generate human hepatocyte-like cells (HLCs) displaying a mixture of
      fetal and adult traits. To improve cell phenotype, we have fully defined our
      differentiation procedure and the cell niche, resulting in the generation of cell
      populations which display improved gene expression and function. While these
      studies mark progress, the ability to generate large quantities of multi well
      plates for screening has been limited by labour intensive procedures and batch to
      batch variation. To tackle this issue, we have developed a semi-automated
      platform to differentiate pluripotent stem cells into HLCs. Stem cell seeding and
      differentiation were performed using liquid handling and automatic pipetting
      systems in 96-well plate format. Following the differentiation, cell phenotype
      was analyzed using automated microscopy and a multi well luminometer.

PMID- 30102284
TI  - Photoelectron Imaging of Anions Illustrated by 310 Nm Detachment of F.
AB  - Anion photoelectron imaging is a very efficient method for the study of energy
      states of bound negative ions, neutral species and interactions of unbound
      electrons with neutral molecules/atoms. State-of-the-art in vacuo anion
      generation techniques allow application to a broad range of atomic, molecular,
      and cluster anion systems. These are separated and selected using time-of-flight
      mass spectrometry. Electrons are removed by linearly polarized photons (photo
      detachment) using table-top laser sources which provide ready access to
      excitation energies from the infra-red to the near ultraviolet. Detecting the
      photoelectrons with a velocity mapped imaging lens and position sensitive
      detector means that, in principle, every photoelectron reaches the detector and
      the detection efficiency is uniform for all kinetic energies. Photoelectron
      spectra extracted from the images via mathematical reconstruction using an
      inverse Abel transformation reveal details of the anion internal energy state
      distribution and the resultant neutral energy states. At low electron kinetic
      energy, typical resolution is sufficient to reveal energy level differences on
      the order of a few millielectron-volts, i.e., different vibrational levels for
      molecular species or spin-orbit splitting in atoms. Photoelectron angular
      distributions extracted from the inverse Abel transformation represent the
      signatures of the bound electron orbital, allowing more detailed probing of
      electronic structure. The spectra and angular distributions also encode details
      of the interactions between the outgoing electron and the residual neutral
      species subsequent to excitation. The technique is illustrated by the application
      to an atomic anion (F-), but it can also be applied to the measurement of
      molecular anion spectroscopy, the study of low lying anion resonances (as an
      alternative to scattering experiments) and femtosecond (fs) time resolved studies
      of the dynamic evolution of anions.

PMID- 30102285
TI  - The Use of Mouse Splenocytes to Assess Pathogen-associated Molecular Pattern
      Influence on Clock Gene Expression.
AB  - From behavior to gene expression, circadian rhythms regulate nearly all aspects
      of physiology. Here, we present a methodology to challenge mouse splenocytes with
      the pathogen-associated molecular patterns (PAMPs) lipopolysaccharide (LPS),
      ODN1826, and heat-killed Listeria monocytogenes and examine their effect on the
      molecular circadian clock. Previously, studies have focused on examining the
      influence of LPS on the molecular clock using a variety of in vivo and ex vivo
      approaches from an assortment of models (e.g., mouse, rat, and human). This
      protocol describes the isolation and challenge of splenocytes, as well as the
      methodology to assess clock gene expression post-challenge via quantitative PCR.
      This approach can be used to assess not only the influence of microbial
      components on the molecular clock but other molecules as well that may alter
      expression of the clock. This approach could be utilized to tease apart the
      molecular mechanism of how PAMP-Toll-like receptor interaction influences clock
      expression.

PMID- 30102286
TI  - Key Elements of Photo Attraction Bioassay for Insect Studies or Monitoring
      Programs.
AB  - Optimized visual attractants will increase insect trapping efficiency by using
      the target insect's innate behaviors (positive photo-taxis) as a means to lure
      the insect into a population control or monitoring trap. Light emitting diodes
      (LEDs) have created customizable lighting options with specific wavelengths
      (colors), intensities, and bandwidths, all of which can be customized to the
      target insects. Photo-attraction behavioral bioassays can use LEDs to optimize
      the attractive color(s) for an insect species down to specific life history
      stages or behaviors (mating, feeding, or seeking shelter). Researchers must then
      confirm the bioassay results in the field and understand the limited attractive
      distance of the visual attractants. The cloverleaf bioassay arena is a flexible
      method to assess photo attraction while also assessing a range of natural insect
      behaviors such as escape and feeding responses. The arena can be used for
      terrestrial or aerial insect experiments, as well as diurnal, and nocturnal
      insects. Data collection techniques with the arena are videotaping, counting
      contact with the lights, or physically collecting the insects as they are
      attracted towards the lights. The assay accounts for insects that make no-choice
      and the arenas can be single (noncompetitive) color or multiple (competitive)
      colors. The cloverleaf design causes insects with strong thigmotaxis to return to
      the center of the arena where they can view all the options in a competitive LED
      tests. The cloverleaf arena presented here has been used with mosquitoes, bed
      bugs, Hessian fly, house flies, biting midges, red flour beetles, and psocids.
      Bioassays are used to develop accurate and effective insect traps to guide the
      development and optimization of insect traps used to monitor pest population
      fluctuations for disease vector risk assessments, the introduction of invasive
      species, and/or be used for population suppression.

PMID- 30102287
TI  - Studying Ribonucleotide Incorporation: Strand-specific Detection of
      Ribonucleotides in the Yeast Genome and Measuring Ribonucleotide-induced
      Mutagenesis.
AB  - The presence of ribonucleotides in nuclear DNA has been shown to be a source of
      genomic instability. The extent of ribonucleotide incorporation can be assessed
      by alkaline hydrolysis and gel electrophoresis as RNA is highly susceptible to
      hydrolysis in alkaline conditions. This, in combination with Southern blot
      analysis can be used to determine the location and strand into which the
      ribonucleotides have been incorporated. However, this procedure is only semi
      quantitative and may not be sensitive enough to detect small changes in
      ribonucleotide content, although strand-specific Southern blot probing improves
      the sensitivity. As a measure of one of the most striking biological consequences
      of ribonucleotides in DNA, spontaneous mutagenesis can be analyzed using a
      forward mutation assay. Using appropriate reporter genes, rare mutations that
      results in the loss of function can be selected and overall and specific mutation
      rates can be measured by combining data from fluctuation experiments with DNA
      sequencing of the reporter gene. The fluctuation assay is applicable to examine a
      wide variety of mutagenic processes in specific genetic background or growth
      conditions.

PMID- 30102288
TI  - A Volumetric Method for Quantification of Cerebral Vasospasm in a Murine Model of
      Subarachnoid Hemorrhage.
AB  - Subarachnoid hemorrhage (SAH) is a subtype of hemorrhagic stroke. Cerebral
      vasospasm that occurs in the aftermath of the bleeding is an important factor
      determining patient outcome and is therefore frequently taken as a study
      endpoint. However, in small animal studies on SAH, quantification of cerebral
      vasospasm is a major challenge. Here, an ex vivo method is presented that allows
      quantification of volumes of entire vessel segments, which can be used as an
      objective measure to quantify cerebral vasospasm. In a first step, endovascular
      casting of the cerebral vasculature is performed using a radiopaque casting
      agent. Then, cross-sectional imaging data are acquired by micro computed
      tomography. The final step involves 3-dimensional reconstruction of the virtual
      vascular tree, followed by an algorithm to calculate center lines and volumes of
      the selected vessel segments. The method resulted in a highly accurate virtual
      reconstruction of the cerebrovascular tree shown by a diameter-based comparison
      of anatomical samples with their virtual reconstructions. Compared with vessel
      diameters alone, the vessel volumes highlight the differences between vasospastic
      and non-vasospastic vessels shown in a series of SAH and sham-operated mice.

PMID- 30102289
TI  - Adipo-Clear: A Tissue Clearing Method for Three-Dimensional Imaging of Adipose
      Tissue.
AB  - Adipose tissue plays a central role in energy homeostasis and thermoregulation.
      It is composed of different types of adipocytes, as well as adipocyte precursors,
      immune cells, fibroblasts, blood vessels, and nerve projections. Although the
      molecular control of cell type specification and how these cells interact have
      been increasingly delineated, a more comprehensive understanding of these adipose
      resident cells can be achieved by visualizing their distribution and architecture
      throughout the whole tissue. Existing immunohistochemistry and immunofluorescence
      approaches to analyze adipose histology rely on thin paraffin-embedded sections.
      However, thin sections capture only a small portion of tissue; as a result, the
      conclusions can be biased by what portion of tissue is analyzed. We have
      therefore developed an adipose tissue clearing technique, Adipo-Clear, to permit
      comprehensive three-dimensional visualization of molecular and cellular patterns
      in whole adipose tissues. Adipo-Clear was adapted from iDISCO/iDISCO+, with
      specific modifications made to completely remove the lipid stored in the tissue
      while preserving native tissue morphology. In combination with light-sheet
      fluorescence microscopy, we demonstrate here the use of the Adipo-Clear method to
      obtain high-resolution volumetric images of an entire adipose tissue.

PMID- 30102290
TI  - Assessment of the Synaptic Interface of Primary Human T Cells from Peripheral
      Blood and Lymphoid Tissue.
AB  - The current understanding of the dynamics and structural features of T-cell
      synaptic interfaces has been largely determined through the use of glass
      supported planar bilayers and in vitro-derived T-cell clones or lines1,2,3,4. How
      these findings apply to the primary human T cells isolated from blood or lymphoid
      tissues is not known, partly due to significant difficulties in obtaining a
      sufficient number of cells for analysis5. Here we address this through the
      development of a technique exploiting multichannel flow slides to build planar
      lipid bilayers containing activating and adhesion molecules. The low height of
      the flow slides promotes rapid cell sedimentation in order to synchronize
      cell:bilayer attachment, thereby allowing researchers to study the dynamic of the
      synaptic interface formation and the kinetics of the granules release. We apply
      this approach to analyze the synaptic interface of as few as 104 to 105 primary
      cryopreserved T cells isolated from lymph nodes (LN) and peripheral blood (PB).
      The results reveal that the novel planar lipid bilayer technique enables the
      study of the biophysical properties of primary human T cells derived from blood
      and tissues in the context of health and disease.

PMID- 30102291
TI  - Identification and Isolation of Oligopotent and Lineage-committed Myeloid
      Progenitors from Mouse Bone Marrow.
AB  - Myeloid progenitors that yield neutrophils, monocytes and dendritic cells (DCs)
      can be identified in and isolated from the bone marrow of mice for hematological
      and immunological analyses. For example, studies of the cellular and molecular
      properties of myeloid progenitor populations can reveal mechanisms underlying
      leukemic transformation, or demonstrate how the immune system responds to
      pathogen exposure. Previously described flow cytometry strategies for myeloid
      progenitor identification have enabled significant advances in many fields, but
      the fractions they identify are very heterogeneous. The most commonly used gating
      strategies define bone marrow fractions that are enriched for the desired
      populations, but also contain large numbers of "contaminating" progenitors. Our
      recent studies have resolved much of this heterogeneity, and the protocol we
      present here permits the isolation of 6 subpopulations of oligopotent and lineage
      committed myeloid progenitors from 2 previously described bone marrow fractions.
      The protocol describes 3 stages: 1) isolation of bone marrow cells, 2) enrichment
      for hematopoietic progenitors by magnetic-activated cell sorting (lineage
      depletion by MACS), and 3) identification of myeloid progenitor subsets by flow
      cytometry (including fluorescence-activated cell sorting, FACS, if desired). This
      approach permits progenitor quantification and isolation for a variety of in
      vitro and in vivo applications, and has already yielded novel insight into
      pathways and mechanisms of neutrophil, monocyte, and DC differentiation.

PMID- 30102292
TI  - In Vitro Reconstitution of Self-Organizing Protein Patterns on Supported Lipid
      Bilayers.
AB  - Many aspects of the fundamental spatiotemporal organization of cells are governed
      by reaction-diffusion type systems. In vitro reconstitution of such systems
      allows for detailed studies of their underlying mechanisms which would not be
      feasible in vivo. Here, we provide a protocol for the in vitro reconstitution of
      the MinCDE system of Escherichia coli, which positions the cell division septum
      in the cell middle. The assay is designed to supply only the components necessary
      for self-organization, namely a membrane, the two proteins MinD and MinE and
      energy in the form of ATP. We therefore fabricate an open reaction chamber on a
      coverslip, on which a supported lipid bilayer is formed. The open design of the
      chamber allows for optimal preparation of the lipid bilayer and controlled
      manipulation of the bulk content. The two proteins, MinD and MinE, as well as
      ATP, are then added into the bulk volume above the membrane. Imaging is possible
      by many optical microscopies, as the design supports confocal, wide-field and
      TIRF microscopy alike. In a variation of the protocol, the lipid bilayer is
      formed on a patterned support, on cell-shaped PDMS microstructures, instead of
      glass. Lowering the bulk solution to the rim of these compartments encloses the
      reaction in a smaller compartment and provides boundaries that allow mimicking of
      in vivo oscillatory behavior. Taken together, we describe protocols to
      reconstitute the MinCDE system both with and without spatial confinement,
      allowing researchers to precisely control all aspects influencing pattern
      formation, such as concentration ranges and addition of other factors or
      proteins, and to systematically increase system complexity in a relatively simple
      experimental setup.

PMID- 30102293
TI  - Nanoparticle-mediated siRNA Gene-silencing in Adult Zebrafish Heart.
AB  - Mammals have a very limited capacity to regenerate the heart after myocardial
      infarction. On the other hand, the adult zebrafish regenerates its heart after
      apex resection or cryoinjury, making it an important model organism for heart
      regeneration study. However, the lack of loss-of-function methods for adult
      organs has restricted insights into the mechanisms underlying heart regeneration.
      RNA interference via different delivery systems is a powerful tool for silencing
      genes in mammalian cells and model organisms. We have previously reported that
      siRNA-encapsulated nanoparticles successfully enter cells and result in a
      remarkable gene-specific knockdown in the regenerating adult zebrafish heart.
      Here, we present a simple, rapid, and efficient protocol for the dendrimer
      mediated siRNA delivery and gene-silencing in the regenerating adult zebrafish
      heart. This method provides an alternative approach for determining gene
      functions in adult organs in zebrafish and can be extended to other model
      organisms as well.

PMID- 30102294
TI  - Development of a synthetic live bacterial therapeutic for the human metabolic
      disease phenylketonuria.
AB  - Phenylketonuria (PKU) is a genetic disease that is characterized by an inability
      to metabolize phenylalanine (Phe), which can result in neurotoxicity. To provide
      a potential alternative to a protein-restricted diet, we engineered Escherichia
      coli Nissle to express genes encoding Phe-metabolizing enzymes in response to
      anoxic conditions in the mammalian gut. Administration of our synthetic strain,
      SYNB1618, to the Pahenu2/enu2 PKU mouse model reduced blood Phe concentration by
      38% compared with the control, independent of dietary protein intake. In healthy
      Cynomolgus monkeys, we found that SYNB1618 inhibited increases in serum Phe after
      an oral Phe dietary challenge. In mice and primates, Phe was converted to trans
      cinnamate by SYNB1618, quantitatively metabolized by the host to hippurate and
      excreted in the urine, acting as a predictive biomarker for strain activity.
      SYNB1618 was detectable in murine or primate feces after a single oral dose,
      permitting the evaluation of pharmacodynamic properties. Our results define a
      strategy for translation of live bacterial therapeutics to treat metabolic
      disorders.

PMID- 30102295
TI  - Targeted delivery of a PD-1-blocking scFv by CAR-T cells enhances anti-tumor
      efficacy in vivo.
AB  - The efficacy of chimeric antigen receptor (CAR) T cell therapy against poorly
      responding tumors can be enhanced by administering the cells in combination with
      immune checkpoint blockade inhibitors. Alternatively, the CAR construct has been
      engineered to coexpress factors that boost CAR-T cell function in the tumor
      microenvironment. We modified CAR-T cells to secrete PD-1-blocking single-chain
      variable fragments (scFv). These scFv-secreting CAR-T cells acted in both a
      paracrine and autocrine manner to improve the anti-tumor activity of CAR-T cells
      and bystander tumor-specific T cells in clinically relevant syngeneic and
      xenogeneic mouse models of PD-L1+ hematologic and solid tumors. The efficacy was
      similar to or better than that achieved by combination therapy with CAR-T cells
      and a checkpoint inhibitor. This approach may improve safety, as the secreted
      scFvs remained localized to the tumor, protecting CAR-T cells from PD-1
      inhibition, which could potentially avoid toxicities associated with systemic
      checkpoint inhibition.

PMID- 30102297
TI  - Correction: A possible new mechanism and drug intervention for kidney damage due
      to arsenic poisoning in rats.
AB  - [This corrects the article DOI: 10.1039/C5TX00165J.].

PMID- 30102296
TI  - Cas9-mediated allelic exchange repairs compound heterozygous recessive mutations
      in mice.
AB  - We report a genome-editing strategy to correct compound heterozygous mutations, a
      common genotype in patients with recessive genetic disorders. Adeno-associated
      viral vector delivery of Cas9 and guide RNA induces allelic exchange and rescues
      the disease phenotype in mouse models of hereditary tyrosinemia type I and
      mucopolysaccharidosis type I. This approach recombines non-mutated genetic
      information present in two heterozygous alleles into one functional allele
      without using donor DNA templates.

PMID- 30102299
TI  - Findings of Research Misconduct.

PMID- 30102298
TI  - ABO histo-blood group and risk of respiratory atopy in children: a review of
      published evidence.
AB  - Besides their fundamental role in transfusion medicine, ABO and other histo-blood
      group antigens are associated with the pathogenesis of some human diseases such
      as malignancy and thrombosis. Reports also show a possible relationship with the
      risk of asthma and other forms of respiratory atopy. This paper aims to
      critically review the current evidence linking ABO histo-blood group with the
      risk of respiratory atopy in children and adults. A literature search was
      conducted with PubMed to gather baseline data about this relationship. The search
      extended to studies published within the past 45 years. First, the molecular
      mechanism underpinning the role of ABO antigenic system in human diseases
      comprises a fascinating relationship with von Willebrand factor and several pro
      inflammatory and adhesion molecules. Second, specific blood group types vary with
      asthma phenotypes; severe asthma is associated with B phenotype, while mild and
      moderate asthma is associated with O and A phenotypes. Third, O phenotype has
      been linked to allergic rhinitis but only in males. Furthermore, asthma risk is
      related to O/Lewis negative/secretor phenotypes, while a significant relationship
      has also been established with B phenotype but not with A and O phenotypes.
      However, one study failed to establish a significant relationship with any of the
      ABO blood group antigens. In conclusion, there is no unanimity on the specific
      histo-blood groups linked to respiratory atopy risk, although asthma phenotypes
      are associated with specific blood groups. Despite the prospect that this
      relationship holds for the use of blood-group typing in evaluating respiratory
      atopy risk in children, more evidence-based studies are still required for its
      validation.

PMID- 30102300
TI  - Comment on "Promising blood-derived biomarkers for estimation of the postmortem
      interval" by I. Costa, F. Carvalho, T. Magalhaes, P. G. de Pinho, R. Silvestre &
      R. J. Dinis-Oliveira. (Toxicol. Res., 2015, 4, 1443-1452).
AB  - Recently, Costa et al. published an article about promising biomarkers for
      estimating the postmortem interval. Instead of postmortem blood, antemortem blood
      was putrefied in vitro by exposing the blood to a temperature gradient. However,
      in this way several other influencing factors were excluded, hence, the accuracy
      of the proposed model is doubtful. Therefore, the aim of this comment is to
      discuss the methodology, results and shortcomings of the study of Costa et al.

PMID- 30102301
TI  - Correction: In vitro toxicity evaluation of silica-coated iron oxide
      nanoparticles in human SHSY5Y neuronal cells.
AB  - [This corrects the article DOI: 10.1039/c5tx00206k.].

PMID- 30102302
TI  - Correction: Arsenic trioxide exposure accelerates colon preneoplasic aberrant
      crypt foci induction regionally through mitochondrial dysfunction.
AB  - [This corrects the article DOI: 10.1039/c7tx00213k.].

PMID- 30102303
TI  - Reply to the 'Comment on "Theoretical studies on a carbonaceous molecular
      bearing: association thermodynamics and dual-mode rolling dynamics"' by E. M.
      Cabaleiro-Lago, J. Rodriguez-Otero and A. Gil, Chem. Sci., 2016, 7, DOI:
      10.1039/C5SC04676A.
AB  - We reply to the comments raised by Cabaleiro-Lago et al. on our article (H. Isobe
      et al., Chem. Sci., 2015, 6, 2746-2753). Here we appreciate the common views we
      share and welcome the clarity this gives, and we discuss and question some of
      their criticisms of the original piece and clarify our opinion in this area. The
      most important answer can be found in the equation, DeltaG = DeltaH - TDeltaS,
      derived from one of the best established fields in physics.

PMID- 30102304
TI  - Achieving ultrahigh carrier mobilities and opening the band gap in two
      dimensional Si2BN.
AB  - Recently, a two-dimensional (2D) Si2BN monolayer material made of silicon, boron
      and nitrogen, was theoretically predicated and has attracted interest in the
      scientific community. Due to its 2D planar nature with high formation energy,
      Si2BN monolayers can be flexible and strong like graphene and also exhibit
      captivating properties like those of other 2D materials. Motivated by this
      fascinating graphene-like monolayer of Si2BN, we have investigated its structural
      and electronic properties based on first-principles calculations. The electronic
      band structure of pure Si2BN shows metallic behaviour. We have discovered that
      the band gap of Si2BN monolayer can be tuned to 102 meV by applying external
      electric fields and mechanical strain. The band gap opening occurs at 5% strain,
      where the bond angles between the nearest neighbours become nearly equal. The
      band gap opening occurs at a small external electric field of 0.4 V A-1. More
      interestingly, at room temperature, the electron mobility of Si2BN is 4.73 * 105
      cm2 V-1 s-1, which is much larger than that of graphene, while the hole mobility
      is 1.11 * 105 cm2 V-1 s-1, slightly smaller than the electron mobility. The
      ultrahigh carrier mobility of Si2BN may lead to many novel applications in high
      performance electronic and optoelectronic devices. These theoretical results
      suggest that the Si2BN monolayer exhibits multiple effects that may significantly
      enhance the performance of Si2BN based electronic devices.

PMID- 30102305
TI  - Design and synthesis of galactose-conjugated fluorinated and non-fluorinated
      proline oligomers: towards antifreeze molecules.
AB  - Galactose-conjugated fluorinated and non-fluorinated proline oligomers that
      exhibit an alpha-helical structure with hydrophilic and lipophilic parts were
      designed as potential antifreeze molecules. These galactose-proline oligomers
      were synthesized and their physical properties were evaluated. Interestingly, the
      non-fluorinated galactose-proline oligomers showed in contrast to the fluorinated
      analogues weak antifreeze activity. The difference in antifreeze activity should
      be attributed to the fluorine gauche effect, which should induce a conformation
      in fluorinated prolines that is different from that of natural proline. The
      results obtained in this study thus suggest that the 3D conformation of the
      galactose-conjugated fluorinated and non-fluorinated proline oligomers is very
      important for their anti-freezing properties.

PMID- 30102311
TI  - Atomic layer oxidation on graphene sheets for tuning their oxidation levels,
      electrical conductivities, and band gaps.
AB  - Graphene sheets that can exhibit electrical conducting and semiconducting
      properties are highly desirable and have potential applications in fiber
      communications, photodetectors, solar cells, semiconductors, and broadband
      modulators. However, there is currently no efficient method that is able to tune
      the band gap of graphene sheets. This work adopts an efficient atomic layer
      oxidation (ALO) technique to cyclically increase the oxidation level of graphene
      sheets, thus, tuning their electrical conductance, band-gap structure, and
      photoluminescence (PL) response. The O/C atomic ratio as an increasing function
      of the ALO cycle number reflects two linear regions: 0.23% per cm2 per cycle (0
      15 cycles) and 0.054% per cm2 per cycle (15-100 cycles). The excellent
      correlation coefficients reveal that the ALO process follows a self-limiting
      route to step-by-step oxidize graphene layers. The interlayer distance of ALO
      graphene sheets shows an obvious increase after the ALO treatment, proved by X
      ray diffraction. As analyzed by X-ray photon spectroscopy, the hydroxyl or epoxy
      group acts as a major contributor to the interlayer spacing distance and
      oxidation extent in the initial ALO stage, as compared to carbonyl and carboxyl
      groups. The ALO mechanism, based on Langmuir-Hinshelwood and Eley-Rideal models,
      is proposed to clarify the formation of oxygen functionalities and structural
      transformation from pristine graphene sheets to oxidized ones during the ALO
      cycle. With a tunable oxidation level, the electrical resistivity, semiconductor
      character, and PL response of ALO-graphene samples can be systematically
      controlled for desired applications. The ALO approach is capable of offering a
      straightforward route to tune the oxidation level of graphene sheets or other
      carbons.

PMID- 30102312
TI  - Bioinspired fiber-like porous Cu/N/C electrocatalyst facilitating electron
      transportation toward oxygen reaction for metal-air batteries.
AB  - Laccase is one of the most effective biocatalysts for oxygen reduction under
      physiological conditions. Its unique Cu- and N-based active sites with direct
      electrical pathways for electrons can guarantee rapid oxygen exchange and
      reduction. Inspired by this specific structure, we designed and fabricated porous
      fiber-like Cu/N/C based on MOFs as an ORR catalyst. Precision morphology control
      of fibers contributed to an increase in the electron transport rate compared with
      that of Cu/N/C nanoparticles, which could minimize interparticle ohmic contacts
      and provide direct electrical pathways along with sufficient active sites to
      catalyze oxygen reduction. The designed Cu/N/C catalyst exhibited similar
      electrochemical activity to that of a commercially available 20 wt% Pt/C ORR
      catalyst. Moreover, after being employed as the cathode of aluminium-air
      batteries, the catalyst outperformed a commercial 5 wt% Pt/C catalyst.

PMID- 30102306
TI  - Branch-PCR constructed TP53 gene nanovector for potential cancer therapy.
AB  - A novel and efficient branch PCR strategy has been used to construct a TP53 gene
      nanovector based on a pair of trimers as primers, which showed unique advantages
      compared to other existing systems for gene delivery and effective potential
      cancer therapy.

PMID- 30102314
TI  - In situ study of nucleation and growth dynamics of Au nanoparticles on MoS2
      nanoflakes.
AB  - Two-dimensional (2D) substrates decorated with metal nanoparticles offer new
      opportunities to achieve high-performance catalytic behavior. However, little is
      known on how the substrates control the nucleation and growth processes of the
      nanoparticles. This paper presents the visualization of dynamic nucleation and
      growth processes of gold nanoparticles on ultrathin MoS2 nanoflakes by in situ
      liquid-cell transmission electron microscopy (TEM). The galvanic displacement
      resulting in Au nuclei formation on MoS2 was observed in real time inside the
      liquid cell. We found that the growth mechanism of Au particles on pristine MoS2
      is in between diffusion-limited and reaction-limited, possibly due to the
      presence of electrochemical Ostwald ripening. A larger size distribution and more
      orientation variation is observed for the Au particles along the MoS2 edge than
      on the interior. Differing from pristine MoS2, sulfur vacancies on MoS2 induce Au
      particle diffusion and coalescence during the growth process. Density functional
      theory (DFT) calculations show that the size difference is because the exposed
      molybdenum atoms at the edge with dangling bonds can strongly interact with Au
      atoms, whereas sulfur atoms on the MoS2 interior have no dangling bonds and
      weakly interact with gold atoms. In addition, S vacancies on MoS2 generate strong
      nucleation centers that can promote diffusion and coalescence of Au
      nanoparticles. The present work provides key insights into the role of 2D
      materials in controlling the size and orientation of noble metal nanoparticles
      vital to the design of next generation catalysts.

PMID- 30102315
TI  - TsOH.H2O-mediated N-amidation of quinoline N-oxides: facile and regioselective
      synthesis of N-(quinolin-2-yl)amides.
AB  - An operationally simple method with 100% atom economy has been developed for the
      synthesis of various N-(quinolin-2-yl)amides via the TsOH.H2O-mediated N
      amidation of quinoline N-oxides using inexpensive and commercially available
      nitriles as the amidation reagents. Mechanistic exploration suggested that the
      reaction probably proceeds through an acid-assisted 1,3-dipolar cycloaddition and
      an N-O bond cleavage followed by a dehydro-aromatization process.

PMID- 30102316
TI  - Three-dimensional assessment of back symmetry in subjects with unilateral
      functional crossbite during the pre-pubertal growth phase: a controlled study.
AB  - Background/Objectives: Since a high prevalence of back anomalies has been
      reported among subjects with crossbite, the aim was to assess the degree of back
      symmetry among subjects with (crossbite) and without (control) unilateral
      functional crossbite during the pre-pubertal growth phase. Methods: A group of 70
      subjects (36 boys, 34 girls; 6.8 +/- 1.2 years) in the primary or mixed dentition
      phase were included. Clinical assessment of head posture, shoulder, scapula and
      hip height were performed with the subject standing, and differences between the
      left and right side greater than 5 mm recorded. Asymmetry of the scapula and
      trunk prominence greater than 8 mm was recorded along with the prominence of
      thoracic and lumbar paravertebral musculature during the forward-bending test.
      Back symmetry was assessed qualitatively and quantitatively on colour deviation
      maps of superimposed mirrored three-dimensional back scans at a tolerance level
      of 2 mm. Results: No significant differences were observed between the groups
      regarding the frequency of clinically assessed back anomalies. The percentage of
      back symmetry was slightly lower in the crossbite than that in the control group
      (71.4 +/- 13.3% and 79.2 +/- 12.1%, respectively). A significant association (P <
      0.05) was seen between scapula plane inclination (OR = 3.41) and scapula
      prominence inequalities (OR = 3.29) and unilateral functional crossbite, while
      hip height inequalities (OR = 0.94) were more frequent in the control group. No
      associations were detected between the side of crossbite and side of prominence
      of back parameters. Limitations: The use of different thresholds for clinical (5
      8 mm) and three-dimensional (2 mm) symmetry assessment. Conclusions: Although
      some degree of back asymmetry was detected in the crossbite group during the pre
      pubertal growth phase, this asymmetry does not appear to be clinically relevant.

PMID- 30102317
TI  - Reply to Suciu et al.

PMID- 30102318
TI  - Is there any correlation between pretreatment haemoglobin levels and prognosis of
      patients with non-small-cell lung cancer?

PMID- 30102319
TI  - Longitudinal 18F-FDG PET imaging in a rat model of autoimmune myocarditis.
AB  - Aims: Although mortality rate is very high, diagnosis of acute myocarditis
      remains challenging with conventional tests. We aimed to elucidate the potential
      role of longitudinal 2-Deoxy-2-18F-fluoro-D-glucose (18F-FDG) positron emission
      tomography (PET) inflammation monitoring in a rat model of experimental
      autoimmune myocarditis. Methods and results: Autoimmune myocarditis was induced
      in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete
      Freund's adjuvant. Time course of disease was assessed by longitudinal 18F-FDG
      PET imaging. A correlative analysis between in- and ex vivo18F-FDG signalling and
      macrophage infiltration using CD68 staining was conducted. Finally,
      immunohistochemistry analysis of the cell-adhesion markers CD34 and CD44 was
      performed at different disease stages determined by longitudinal 18F-FDG PET
      imaging. After immunization, myocarditis rats revealed a temporal increase in 18F
      FDG uptake (peaked at week 3), which was followed by a rapid decline thereafter.
      Localization of CD68 positive cells was well correlated with in vivo18F-FDG PET
      signalling (R2 = 0.92) as well as with ex vivo18F-FDG autoradiography (R2 = 0.9,
      P < 0.001, respectively). CD44 positivity was primarily observed at tissue
      samples obtained at acute phase (i.e. at peak 18F-FDG uptake), while CD34
      positive staining areas were predominantly identified in samples harvested at
      both sub-acute and chronic phases (i.e. at 18F-FDG decrease). Conclusion: 18F-FDG
      PET imaging can provide non-invasive serial monitoring of cardiac inflammation in
      a rat model of acute myocarditis.

PMID- 30102320
TI  - Corrigendum to: 'Robotic mitral valve replacements with bioprosthetic valves in
      52 patients: experience from a tertiary referral hospital'  [Eur J Cardiothorac
      Surg 2018;54:853--9].

PMID- 30102321
TI  - Inequality in oral anticoagulation use and clinical outcomes in atrial
      fibrillation: a Danish nationwide perspective.
AB  - Aim: To explore the potential of small-area variation analysis as a tool for
      identifying unwarranted variation in oral anticoagulation (OAC) use and clinical
      outcomes in patients with atrial fibrillation (AF) and thereby identify locations
      with opportunity for improvement in AF care. Methods and results: Based on Danish
      health care registries, we conducted a nationwide historical cohort study
      including first-time AF patients with a CHA2DS2-VASc (congestive heart failure,
      hypertension, age >= 75, diabetes, thromboembolism, vascular disease, age 65-74,
      and sex category) score >= 2 between 2007 and 2014 (n = 94 482). For each
      administrative region and municipality, we assessed OAC initiation and
      persistence as well as the risk of ischaemic stroke, haemorrhagic stroke, and
      other major bleeding, respectively. In addition, potential temporal changes were
      examined for all outcomes. Initiation of OAC varied among regions from 49.5% to
      62.4%. In patients initiating OAC, the proportion of patients still receiving OAC
      after 1 year varied from 73.9% to 79.3%. Oral anticoagulation use increased in
      all regions during the study period, particularly after 2010, but regional
      variation in OAC initiation persisted. Generally, the regions and municipalities
      with the highest initiation of OAC also had the highest OAC persistence. The risk
      of ischaemic stroke and other major bleeding was lower in these regions and
      municipalities. We found no significant difference between regions in risk of
      haemorrhagic stroke. Conclusion: Substantial geographical variation in OAC use
      and clinical outcomes occurs in Denmark demonstrating the potential of small-area
      variation analysis as a tool for identifying unwarranted variation in AF care and
      clinical outcomes. Our findings demonstrate the need for additional initiatives
      to ensure uniform high-quality care for AF patients.

PMID- 30102322
TI  - The double jeopardy of aortic stenosis in cancer patients.

PMID- 30102324
TI  - Proteasome inhibitors for multiple myeloma.
AB  - Therapeutic strategies for multiple myeloma have dramatically changed in the last
      two decades, especially after the introduction of proteasome inhibitors. The
      first-in-class proteasome inhibitor, bortezomib, was approved by the US Food and
      Drug Administration in 2003. Since then, it has been a backbone therapy for not
      only relapsed or refractory myeloma patients but also newly diagnosed multiple
      myeloma patients. Second-generation proteasome inhibitors, such as carfilzomib
      and ixazomib, have been approved, and three proteasome inhibitors were
      incorporated into several regimens with other cytotoxic agents, such as
      alkylating agents, immunomodulatory drugs and monoclonal antibodies. Because each
      proteasome inhibitor shows different properties with respect to adverse events,
      understanding and managing each adverse event of proteasome inhibitors are
      necessary for the continuation of therapy with minimal interruption of treatment.
      This review summarizes the recent advances in proteasome inhibitors used in the
      treatment of multiple myeloma.

PMID- 30102323
TI  - Selective sets of mRNAs localize to extracellular paramural bodies in a rice
      glup6 mutant.
AB  - The transport of rice glutelin storage proteins to the storage vacuoles requires
      the Rab5 GTPase and its related guanine nucleotide exchange factor (Rab5-GEF).
      Loss of function of these membrane vesicular trafficking factors results in the
      initial secretion of storage proteins and later their partial engulfment by the
      plasma membrane to form an extracellular paramural body (PMB), an aborted
      endosome complex. Here, we show that in the rice Rab5-GEF mutant glup6, glutelin
      RNAs are specifically mislocalized from their normal location on the cisternal
      endoplasmic reticulum (ER) to the protein body-ER, and are also apparently
      translocated to the PMBs. We substantiated the association of mRNAs with this
      aborted endosome complex by RNA-seq of PMBs purified by flow cytometry. Two PMB
      associated groups of RNA were readily resolved: those that were specifically
      enriched in this aborted complex and those that were highly expressed in the
      cytoplasm. Examination of the PMB-enriched RNAs indicated that they were not a
      random sampling of the glup6 transcriptome but, instead, encompassed only a few
      functional mRNA classes. Although specific autophagy is also an alternative
      mechanism, our results support the view that RNA localization may co-opt membrane
      vesicular trafficking, and that many RNAs that share function or intracellular
      location are co-transported in developing rice seeds.

PMID- 30102325
TI  - Dosimetric comparison between dual-isocentric dynamic conformal arc therapy and
      mono-isocentric volumetric-modulated arc therapy for two large brain metastases.
AB  - Mono-isocentric volumetric-modulated arc therapy (VMAT) can be used to treat
      multiple brain metastases. It remains unknown whether mono-isocentric VMAT can
      improve the dose distribution compared with dual-isocentric dynamic conformal arc
      therapy (DCAT), especially for two brain metastases. We compared the dose
      distribution between dual-isocentric DCAT and mono-isocentric VMAT for two large
      brain metastases, and analyzed the relationship between the distance between the
      two targets and the difference in dose distribution. A total of 19 patients, each
      with two large brain metastases, were enrolled. The dose prescribed for each
      planning target volume (PTV) was 28 Gy in five fractions (D99.8 = 100%). We
      created new indices derived from conformity indices suggested by the Radiation
      Therapy Oncology Group (RTOG; mRTOG-CI) and Paddick et al. (mIP-CI), using the
      dosimetric parameters of the sum of the two PTVs. The median PTV was 5.05 cm3
      (range, 2.10-28.47). VMAT significantly improved mRTOG-CI and mIP-CI compared
      with DCAT. In all cases, VMAT was able to improve mRTOG-CI and mIP-CI compared
      with DCAT. Whereas the normal brain volume receiving 5 Gy was similar between the
      two modalities, the normal brain receiving 10, 12, 15, 20, 25 and 28 Gy (V10-V28)
      was significantly smaller in VMAT. The mean beam-on times were 213.3 s and 121.9
      s in DCAT and VMAT, respectively (P < 0.001). Mono-isocentric VMAT improved the
      target conformity and reduced the beam-on time and V10-V28 of the normal brain
      for not only two close metastases but also two distant metastases. Mono
      isocentric VMAT seems to be a promising treatment technique for two large brain
      metastases.

PMID- 30102327
TI  - Susceptibility and Vectorial Capacity of American Aedes albopictus and Aedes
      aegypti (Diptera: Culicidae) to American Zika Virus Strains.
AB  - The rapid expansion of Zika virus (ZIKV), following the recent outbreaks of
      Chikungunya virus, overwhelmed the public health infrastructure in many countries
      and alarmed many in the scientific community. Aedes aegypti (L.) (Diptera:
      Culicidae) and Aedes albopictus (Skuse) (Diptera: Culicidae) have previously been
      incriminated as the vectors of these pathogens in addition to dengue virus. In
      our study, we challenged low generation Ae. aegypti (Chiapas, Mexico) and Ae.
      albopictus (North Carolina, Mississippi), with three strains of ZIKV, Puerto Rico
      (GenBank: KU501215), Honduras (GenBank: KX694534), and Miami (GenBank: MF988743).
      Following an oral challenge with 107.5 PFU/ml of the Puerto Rico strain, we
      observed high infection and dissemination rates in both species (95%). We report
      estimated transmission rates for both species (74 and 33%, for Ae. aegypti (L.)
      (Diptera: Culicidae) and Ae. albopictus (Skuse) (Diptera: Culicidae),
      respectively), and the presence of a probable salivary gland barrier in Ae.
      albopictus to Zika virus. Finally, we calculated vectorial capacity for both
      species and found that Ae. albopictus had a slightly lower vectorial capacity
      when compared with Ae. aegypti.Second Language Abstract: La rapida expansion del
      virus Zika, poco despues de las epidemias de chikungunya, rebaso la
      infraestructura de salud publica en muchos paises y sorprendio a muchos en la
      comunidad cientifica. Notablemente, Aedes aegypti y Aedes albopictus transmiten
      estos patogenos ademas del virus del dengue. En este estudio se expusieron con
      tres cepas americanas de virus Zika a grupos de Aedes aegypti y Aedes albopictus
      de generacion reciente. Encontramos altos porcentajes de infeccion y diseminacion
      en ambas especies (95%). Se reporta, la transmision viral en ambas especies (74 y
      33%, para Aedes aegypti and Aedes albopictus, respectivamente) y una probable
      barrera a nivel de glandulas salivarias. Finalmente, calculamos la capacidad
      vectorial para ambas especies.

PMID- 30102326
TI  - Impact of prophylactic cranial irradiation on pattern of brain metastases as a
      first recurrence site for limited-disease small-cell lung cancer.
AB  - This study sought to evaluate the impact of prophylactic cranial irradiation
      (PCI) on the pattern of brain recurrence after radical treatment in patients with
      limited-disease small-cell lung cancer (LD-SCLC). Patients treated with
      radiotherapy and chemotherapy between January 2006 and December 2014 at a single
      institution were retrospectively examined. Radiotherapy was performed using
      accelerated hyperfractionated radiotherapy (twice daily, 45 Gy in 30 fractions)
      or conventional fractionated radiotherapy (once daily, 50 Gy in 25 fractions).
      The chemotherapy regimen consisted of intravenous platinum-etoposide. A total of
      162 patients were included and the median follow-up duration was 38 months.
      Ninety-three patients underwent PCI, and the 3-year overall survival (OS) rates
      were 14% among patients without PCI and 41% among those with PCI (P < 0.001). The
      frequency of brain metastases as a first recurrence site (BMFR) was significantly
      lower among patients who underwent PCI, compared with those who did not (P =
      0.002). The median time to the l of BMFR was significantly shorter among patients
      without PCI than among those with PCI (P = 0.012). In addition, 68% of the BMFR
      patients who did not undergo PCI exhibited five or more lesions, while only 12%
      of BMFR patients who did undergo PCI exhibited five or more lesions (P < 0.001).
      PCI had a significant positive impact on patient prognosis after radical
      treatment for LD-SCLC, and the difference in the number of, and time to the
      appearance of, BMFR between patients treated with PCI and those treated without
      PCI might affect the clinical outcomes.

PMID- 30102328
TI  - Medication adherence is associated with an increased risk of cancer in kidney
      transplant recipients: a cohort study.
AB  - Background: Nonadherence to posttransplant immunosuppressive medication is
      associated with increased rates of rejection and graft loss, yet it is unknown to
      what degree ideal adherence is associated with the sequelae of
      overimmunosuppression. Specifically, we questioned whether excellent adherence
      increased the posttransplant cancer risk. Methods: Between August 1998 and August
      2006, 195 consenting kidney transplant recipients had electronic monitoring of
      theirimmunosuppressive medication adherence. Results: Based on their average
      quantitative adherence to a single immunosuppressant drug over the first 6 months
      posttransplant, recipients were grouped into adherence tertiles (highest, >97.9%
      adherence; middle, 91-97.8%; lowest, <91%). The cumulative incidence of cancer
      was calculated for patients in each tertile, treating death as a competing risk.
      The association between adherence and cancer rate was calculated after adjusting
      for recipient risk factors, using a competing risk proportional hazards model.
      The median duration of follow-up was 10.1 years. The 10-year estimated cumulative
      cancer incidence was 59.4% in the most adherent, 36.1% in the middle group and
      38.1% in the least adherent group (P = 0.006). Excluding nonmelanocytic skin
      cancers, cancer incidence remained significantly higher in the highest adherence
      group (P = 0.002). Conclusions: These data provide additional support for the
      need to individualize immunosuppression to minimize both rejection and
      immunosuppressive drug-related complications including cancer.

PMID- 30102329
TI  - Hypoalbuminemia: a price worth paying for improved dialytic removal of middle
      molecular-weight uremic toxins?
AB  - Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic
      toxins and may improve outcomes in patients with end-stage kidney disease (ESKD),
      but it requires complex equipment and comes with risks associated with infusion
      of large volumes of substitution solution. New high-flux hemodialysis membranes
      with improved diffusive permeability profiles do not have these limitations and
      offer an attractive alternative to HDF. However, both strategies are associated
      with increased albumin loss into the dialysate, raising concerns about the
      potential for decreased serum albumin concentrations that have been associated
      with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in
      ESKD, including protein energy wasting, inflammation, volume expansion, renal
      loss and loss into the dialysate; of these factors, loss into the dialysate is
      not necessarily the most important. Furthermore, recent studies suggest that mild
      hypoalbuminemia per se is not an independent predictor of increased mortality in
      dialysis patients, but in combination with inflammation it is a poor prognostic
      sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and
      mortality may depend on the presence or absence of inflammation. In this review
      we summarize recent findings on the role of dialysate losses in hypoalbuminemia
      and the importance of concomitant inflammation on outcomes in patients with ESKD.
      Based on these findings, we discuss whether hypoalbuminemia may be a price worth
      paying for increased dialytic removal of middle-molecular-weight uremic toxins.

PMID- 30102330
TI  - Incidence, prevalence, mortality and chronic renal damage of anti-neutrophil
      cytoplasmic antibody-associated glomerulonephritis in a 20-year population-based
      cohort.
AB  - Background: True population-based clinical and outcomes data are lacking for anti
      neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis (AAGN).
      Therefore we aimed to estimate the incidence, prevalence and mortality of AAGN,
      as well as the relationship between the grade of chronic renal damage at
      presentation and renal and non-renal outcomes. Methods: Patients with AAGN were
      identified among a population-based incident cohort of 57 Olmsted County
      residents diagnosed with ANCA-associated vasculitis (AAV) in 1996-2015. Incidence
      rates were age and sex adjusted to the 2010 US white population. Age- and sex
      adjusted prevalence was calculated for 1 January 2015. Survival rates were
      compared with expected rates in the Minnesota population. Chronic renal damage
      was assessed by chronicity score (CS) on biopsies performed at diagnosis.
      Results: Thirty-four (60%) patients had AAGN. Of these, 65% had microscopic
      polyangiitis (MPA) and 74% were myeloperoxidase (MPO)-ANCA positive. The annual
      incidence of AAGN was 2.0/100 000 population [95% confidence interval (CI) 1.3
      2.7] and the overall prevalence was 35/100 000 (95% CI 24-47). Mortality for AAGN
      was increased (P < 0.001), whereas mortality for AAV without glomerulonephritis
      did not differ from the general population. Minimal to mild CS predicted recovery
      of renal function at 1 year; clinical diagnosis (granulomatosis with polyangiitis
      versus MPA) and ANCA specificity (proteinase 3 versus MPO) did not. This
      observation was replicated in an independent cohort of 38 newly diagnosed AAGN
      patients seen at our centre over the 1999-2014 period. Conclusions: The annual
      incidence and prevalence of AAGN in Minnesota are 2.0/100 000 and 35/100 000,
      respectively. Mortality is worse compared with AAV patients without
      glomerulonephritis. More advanced renal damage at diagnosis predicts less renal
      recovery.

PMID- 30102331
TI  - Conserved sequences in the Drosophila mod(mdg4) intron promote poly(A)
      independent transcription termination and trans-splicing.
AB  - Alternative splicing (AS) is a regulatory mechanism of gene expression that
      greatly expands the coding capacities of genomes by allowing the generation of
      multiple mRNAs from a single gene. In Drosophila, the mod(mdg4) locus is an
      extreme example of AS that produces more than 30 different mRNAs via trans
      splicing that joins together the common exons and the 3' variable exons generated
      from alternative promoters. To map the regions required for trans-splicing, we
      have developed an assay for measuring trans-splicing events and identified a 73
      bp region in the last common intron that is critical for trans-splicing of three
      pre-mRNAs synthesized from different DNA strands. We have also found that
      conserved sequences in the distal part of the last common intron induce
      polyadenylation-independent transcription termination and are enriched by paused
      RNA polymerase II (RNAP II). These results suggest that all mod(mdg4) mRNAs are
      formed by joining in trans the 5' splice site in the last common exon with the 3'
      splice site in one of the alternative exons.

PMID- 30102333
TI  - Circulating ADAMs are associated with renal and cardiovascular outcomes in
      chronic kidney disease patients.
AB  - Background: A disintegrin and metalloproteinase (ADAM) 17, also known as tumour
      necrosis factor alpha-converting enzyme (TACE), is a metalloproteinase that
      releases the ectodomains of most growth factors, cytokines, receptors and enzymes
      and has been associated with the presence of chronic kidney disease (CKD) and
      cardiovascular (CV) disease. The role of circulating ADAMs in the progression of
      renal function and CV events in CKD patients is unknown. Methods: A total of 2570
      subjects from an observational and multicentre study with CKD Stages 3-5, CKD
      Stage 5D and controls without any history of CV disease were studied. Circulating
      ADAM activity was assessed using a fluorometric technique. Progression of renal
      disease was defined as a 30% increase in serum creatinine or dialysis requirement
      after 24 months of follow-up. CV outcomes were assessed after 48 months of follow
      up. Results: Patients with advanced CKD had higher ADAM activity as compared with
      patients with moderate CKD or controls. Male patients with progression of CKD had
      higher ADAM levels at baseline compared with patients with stable renal function
      {22.19 relative fluorescence units/MUL/h [95% confidence interval (CI) 11.22
      37.32] versus 12.15 (7.02-21.50)}. After multivariate adjustment, higher ADAM
      activity was identified as a risk factor for progression of CKD in male patients
      [30% increase in the creatinine odds ratio (OR) 2.72 (95% CI 1.58-4.68), P <
      0.001; dialysis requirement OR 3.00 (95% CI 1.65-5.46), P < 0.001; dialysis
      requirement or 30% increase in the creatinine OR 3.15 (95% CI 2.06-4.81), P <
      0.001]. ADAM activity was also identified as an independent risk factor for CV
      events [hazard ratio (HR) 1.68 (95% CI 1.20-2.36), P = 0.003]. Conclusions: High
      ADAMs activity levels are independently associated with CKD progression in males
      and with CV events in CKD patients.

PMID- 30102332
TI  - Schizosaccharomyces pombe Pol II transcription elongation factor ELL functions as
      part of a rudimentary super elongation complex.
AB  - ELL family transcription factors activate the overall rate of RNA polymerase II
      (Pol II) transcription elongation by binding directly to Pol II and suppressing
      its tendency to pause. In metazoa, ELL regulates Pol II transcription elongation
      as part of a large multisubunit complex referred to as the Super Elongation
      Complex (SEC), which includes P-TEFb and EAF, AF9 or ENL, and an AFF family
      protein. Although orthologs of ELL and EAF have been identified in lower
      eukaryotes including Schizosaccharomyces pombe, it has been unclear whether SEC
      like complexes function in lower eukaryotes. In this report, we describe
      isolation from S. pombe of an ELL-containing complex with features of a
      rudimentary SEC. This complex includes S. pombe Ell1, Eaf1, and a previously
      uncharacterized protein we designate Ell1 binding protein 1 (Ebp1), which is
      distantly related to metazoan AFF family members. Like the metazoan SEC, this S.
      pombe ELL complex appears to function broadly in Pol II transcription.
      Interestingly, it appears to have a particularly important role in regulating
      genes involved in cell separation.

PMID- 30102334
TI  - Cell membrane proteins with high N-glycosylation, high expression, and multiple
      interaction partners are preferred by mammalian viruses as receptors.
AB  - Motivation: Receptor mediated entry is the first step for viral infection.
      However, the question of how viruses select receptors remains unanswered.
      Results: Here, by manually curating a high-quality database of 268 pairs of
      mammalian virus-host receptor interaction, which included 128 unique viral
      species or sub-species and 119 virus receptors, we found the viral receptors are
      structurally and functionally diverse, yet they had several common features when
      compared to other cell membrane proteins: more protein domains, higher level of N
      glycosylation, higher ratio of self-interaction and more interaction partners,
      and higher expression in most tissues of the host. This study could deepen our
      understanding of virus-receptor interaction. Availability: The database of
      mammalian virus-host receptor interaction is available at
      http://www.computationalbiology.cn:5000/viralReceptor. Supplementary information:
      Supplementary data are available at Bioinformatics online.

PMID- 30102335
TI  - CharGer: Clinical Characterization of Germline Variants.
AB  - Summary: CharGer (Characterization of Germline variants) is a software tool for
      interpreting and predicting clinical pathogenicity of germline variants. CharGer
      gathers evidence from databases and annotations, provided by local tools and
      files or via ReST APIs, and classifies variants according to ACMG guidelines for
      assessing variant pathogenicity. User-designed pathogenicity criteria can be
      incorporated into CharGer's flexible framework, thereby allowing users to create
      a customized classification protocol. Availability: Source code is freely
      available at https://github.com/ding-lab/CharGer and is distributed under the GNU
      GPL-v3.0 license. Software is also distributed through the Python Package Index
      (PyPI) repository. CharGer is implemented in Python 2.7 and is supported on Unix
      based operating systems. Supplementary information: Supplementary data are
      available at Bioinformatics online.

PMID- 30102336
TI  - Semaphorin-3A inhibits multiple myeloma progression in a mouse model.
AB  - Previous studies revealed that progression of multiple myeloma (MM) is associated
      with downregulation of semaphorin-3A (sema3A) expression in bone marrow
      endothelial cells. We therefore determined if serum sema3A concentrations are
      correlated with MM progression and if sema3A can affect MM progression. We find
      that the concentration of sema3A in sera of MM patients is strongly reduced and
      that the decrease is correlated with disease progression. A similar depletion is
      found in patients having acute myeloid leukemia and acute lymphoblastic leukemia
      but not in cancer forms that do not involve the bone marrow such as in colon
      cancer. Expression of a modified sema3A [furin-resistant sema3A (FR-sema3A)]
      stabilized against cleavage by furin-like proprotein convertases in CAG MM cells
      did not affect their behavior in-vitro. CAG cells injected into the tail vein of
      severe combined immunodeficient (SCID) mice home to the bone marrow and
      proliferate, mimicking MM disease progression. Disease progression in mice
      injected with CAG cells expressing FR-sema3A was inhibited, resulting in
      prolonged survival and a lower incidence of bone lesions. Histological
      examination and fluorescence-activated cell sorting analysis revealed that FR
      sema3A expression reduced the infiltration of the CAG cells into the bone marrow,
      reduced bone marrow necrosis and reduced angiogenesis induced by the MM cells in
      the bone marrow. Our results suggest that measurement of sema3A serum
      concentrations may be of use for the diagnosis and for the monitoring of
      malignancies of the bone marrow such as MM. Furthermore, our results suggest that
      FR-sema3A may perhaps find use as an inhibitor of MM disease progression.

PMID- 30102337
TI  - FAT1 Somatic Mutations in Head and Neck Carcinoma are Associated with Tumor
      Progression and Survival.
AB  - In recent years, the incidence and mortality rates of head and neck squamous cell
      carcinoma (HNSCC) have increased worldwide. Therefore, understanding genomic
      alterations in HNSCC carcinogenesis is crucial for appropriate diagnosis and
      therapy. Procadherin FAT1, which encodes 4588 amino acid residues, regulates
      complex mechanisms to promote oncogenesis or suppression of malignancies.
      Multiplex polymerase chain reaction (PCR)-based next-generation sequencing (NGS)
      revealed FAT1 somatic mutations. The clinicopathologic implications of FAT1 in
      HNSCC were investigated using expression assays, and the functional role of FAT1
      in HNSCC pathogenesis was determined using ectopic expression and knockdown
      experiments. Approximately 29% of patients with HNSCC harbored damaging FAT1
      mutations. InVEx identified FAT1 as a significant functional mutation burden.
      Each type of mutation (missense, nonsense, and frameshift mutations) accounted
      for nearly one-third of deleterious mutations. FAT1 mutations correlated with
      lower FAT1 expression in tumors. The knockdown of the endogenous expression of
      FAT1 and exogenous expression of crucial FAT1 domains unequivocally indicated
      that FAT1 suppressed the migration and invasion capability of HNSCC cells.
      Functional analysis suggested that nonsense mutations in FAT1 result in the loss
      of the suppression of tumor progression. FAT1 mutations and downregulation
      defined nodal involvement, lymphovascular permeation, and tumor recurrence. In
      addition, FAT1 mutations and downregulation are independent predictors of poor
      disease-free survival in patients with HNSCC. This study is the first to perform
      multiplex PCR-based NGS to indicate marked nonsynonymous FAT1 mutations in HNSCC,
      which are prognostic indicators. The gene analysis strategy proposed for
      detecting FAT1 mutations may be a valid method for mutation screening.

PMID- 30102338
TI  - Identification of genomic alterations in nasopharyngeal carcinoma and
      nasopharyngeal carcinoma-derived Epstein-Barr virus by whole genome sequencing.
AB  - Nasopharyngeal carcinoma (NPC) is a common tumor in Southern China with marked
      ethnic and geographic distributions and concomitant EBV infection. However, the
      molecular basis of NPC remains largely unknown and the role of EBV genomic
      variations in the pathogenesis of NPC is unclear. Whole-genome sequencing of a
      collection of 12 EBV-positive paired NPC tumor/peripheral blood samples from
      Hunan province was performed, and the FBXO11 gene was subjected to further
      functional analyses. We identified 69 missense mutations in signaling pathways
      typically altered in cancer, including NF-kappaB and Wnt/Hedgehog/Notch.
      Additionally, 122 variations were identified in non-coding regions. Among these,
      a subset of genes was confirmed as dysregulated in NPC by mining the NPC cDNA
      microarray database. The randomly selected gene, FBXO11, could promote the
      malignant progression of NPC in vitro. Full-length EBV genomes from 8 of the 12
      patients with NPC were also successfully assembled, and latent EBV infection is a
      primary cause of NPC. The various subtypes of EBV detected exhibited clear
      correlations with its geographical distribution. This study has explored novel
      biological markers and tumorigenic pathways with substantial potential to enhance
      therapeutic strategies for NPC.

PMID- 30102339
TI  - A quantitative map of protein sequence space for the cis-defensin superfamily.
AB  - Motivation: The cis-defensins are a superfamily of small, cationic, cysteine-rich
      proteins, sharing a common scaffold, but highly divergent sequences and varied
      functions from host-defence to signalling. Superfamily members are most abundant
      in plants (with some genomes containing hundreds of members), but are also found
      across fungi and invertebrates. However, of the thousands of cis-defensin
      sequences in databases, only have a handful have solved structures or assigned
      activities. Non-phylogenetic sequence-analysis methods are therefore necessary to
      use the relationships within the superfamily to classify members, and to predict
      and engineer functions. Results: We show that the generation of a quantitative
      map of sequence space allows these highly divergent sequences to be usefully
      analysed. This information-rich technique can identify natural groupings of
      sequences with similar biophysical properties, detect interpretable covarying
      properties, and provide information on typical or intermediate sequences for each
      cluster. The cis-defensin superfamily contains clearly-defined groups,
      identifiable based on their biophysical properties and motifs. The organisation
      of sequences within this space also provides a foundation of understanding the
      ancient evolution of the superfamily. Availability: A webtool for exploring and
      querying the space is hosted at TS404.shinyapps.io/DefSpace. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30102340
TI  - Ignoring the Elephant: Does the Infectious Diseases Society of America Support
      Sepsis-3 or Pre-sepsis Criteria?

PMID- 30102342
TI  - isiKnock: in silico knockouts in signaling pathways.
AB  - Summary: isiKnock is a new software that automatically conducts in silico
      knockouts for mathematical models of signaling pathways. The software allows for
      the prediction of the behavior of biological systems after single or multiple
      knockout. The implemented algorithm applies transition invariants and the novel
      concept of Manatee invariants. A knockout matrix visualizes the results. The tool
      enables the analysis of dependencies, for example, in signal flows from the
      receptor activation to the cell response at steady state. Availability and
      Implementation: isiKnock is an open-source tool, freely available at
      http://www.bioinformatik.uni-frankfurt.de/tools/isiKnock/. It requires at least
      Java 8 and runs under Microsoft Windows, Linux, and Mac OS.

PMID- 30102341
TI  - Characterization of the ICCE Repeat in Mammals Reveals an Evolutionary
      Relationship with the DXZ4 Macrosatellite through Conserved CTCF Binding Motifs.
AB  - Appreciation is growing for how chromosomes are organized in three-dimensional
      space at interphase. Microscopic and high throughput sequence-based studies have
      established that the mammalian inactive X chromosome (Xi) adopts an alternate
      conformation relative to the active X chromosome. The Xi is organized into
      several multi-megabase chromatin loops called superloops. At the base of these
      loops are superloop anchors, and in humans three of these anchors are composed of
      large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA
      Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains
      a high density of binding sites for the architectural organization protein CCCTC
      binding factor (CTCF) which exclusively associates with the Xi allele in normal
      cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome.
      In this study, we report the characterization of the ICCE tandem repeat, for
      which very little is known. ICCE is embedded within an intron of the Nobody
      (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of
      ICCE is only retained in higher primates, but that ICCE orthologs exist beyond
      the primate lineage. Like DXZ4, what is conserved is organization of the
      underlying DNA into a large tandem repeat, physical location within the NBDY
      locus and conservation of short DNA sequences corresponding to specific CTCF and
      Yin Yang 1 binding motifs that correlate with female-specific DNA
      hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals.
      Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4
      motif and support an evolutionary relationship between DXZ4 and ICCE.

PMID- 30102343
TI  - Reply to Al-Hasan and Justo.

PMID- 30102344
TI  - Geometric morphometric analysis of the palatal morphology in growing subjects
      with skeletal open bite.
AB  - Objectives: To assess the morphological shape variations of the palatal vault in
      Open Bite (OB) growing subjects when compared with a Control Group (CG) by means
      of Geometric Morphometric Method (GMM). Materials and methods: The OB Group (OBG)
      consisted of 75 subjects (39 females, 36 males; mean age: 8.5 +/- 0.8 years) who
      were collected retrospectively with the following inclusion criteria: European
      ancestry, overbite less than 0 mm, mixed dentition stage, prepubertal skeletal
      maturation (CS1-CS2), hyperdivergent skeletal pattern (SN^GoGn > 37 degrees ).
      The OBG was compared with a CG of 46 prepubertal subjects presenting normal
      occlusion (24 females, 22 males; mean age of 8.3 +/- 1.7 years). For each
      subject, lateral cephalograms and maxillary dental casts were available.
      Landmarks and semilandmarks were digitized on digital dental casts and GMM was
      applied. Procrustes analysis and principal component analysis (PCA) were
      performed. OBG was divided in two subgroups: Sucking Habits Group (SHG) (39
      subjects) and Non-Sucking Habits Group (NSHG) (36 subjects). Results: PC1 showed
      significant morphological changes in transverse and vertical dimensions with OBG
      palates higher and narrower when compared with CG. When comparing the two
      subgroups no statistically significant differences were found. NSHG demonstrated
      a slight reduction of the transverse dimension and a deeper palatal vault respect
      to SHG. Limitations: The limitations of this study were the division of OBG in
      two subgroups based on referral of thumb sucking habits without assessing the
      duration and the intensity of thumb sucking. Conclusions: OB subjects presented
      with a significant constriction of the maxillary arch when compared with CG. The
      morphological palatal shape variations in OBG were not influenced by the presence
      or absence of non-nutritive sucking habits.

PMID- 30102345
TI  - Interactive effects of dissolved nitrogen, phosphorus and litter chemistry on
      stream fungal decomposers.
AB  - The enrichment of ecosystems by nutrients such as nitrogen (N) and phosphorus (P)
      has important ecological consequences. These include effects on plant litter
      decomposition in forest soils and forested headwater streams, where fungi play a
      pivotal role. However, our understanding of nutrient relationships on fungal
      communities associated with decomposing litter remains surprisingly incomplete.
      We conducted a fully factorial microcosm experiment with known communities of
      fungal decomposers from streams to assess the importance of dissolved N and P
      supply, as well as the atomic nutrient ratio (N:P), on fungal community
      succession, diversity, biomass and reproduction on three leaf-litter species
      differing in nutrient and lignin concentrations. Fungal biomass accrual and spore
      production were strongly controlled by external N supply, whereas P supply was
      much less important. The magnitude of these effects was mediated by litter
      quality, with stronger effects of dissolved N and P on lignin-poor and high N:P
      litter. N supply also influenced fungal diversity and species composition, acting
      as a pacemaker of community succession. Collectively, our data indicate that N
      was in much greater demand than predicted by standard stoichiometric models. The
      most parsimonious explanation for this deviation relates to the need of litter
      fungi to invest large amounts of N into degradative exoenzymes.

PMID- 30102346
TI  - Are all children born the same?

PMID- 30102347
TI  - Exploring the Limits and Causes of Plastid Genome Expansion in Volvocine Green
      Algae.
AB  - Plastid genomes are not normally celebrated for being large. But researchers are
      steadily uncovering algal lineages with big and, in rare cases, enormous plastid
      DNAs (ptDNAs), such as volvocine green algae. Plastome sequencing of five
      different volvocine species has revealed some of the largest, most repeat-dense
      plastomes on record, including that of Volvox carteri (~525 kb). Volvocine algae
      have also been used as models for testing leading hypotheses on organelle genome
      evolution (e.g., the mutational hazard hypothesis), and it has been suggested
      that ptDNA inflation within this group might be a consequence of low mutation
      rates and/or the transition from a unicellular to multicellular existence. Here,
      we further our understanding of plastome size variation in the volvocine line by
      examining the ptDNA sequences of the colonial species Yamagishiella unicocca and
      Eudorina sp. NIES-3984 and the multicellular Volvox africanus, which are
      phylogenetically situated between species with known ptDNA sizes. Although V.
      africanus is closely related and similar in multicellular organization to V.
      carteri, its ptDNA was much less inflated than that of V. carteri. Synonymous-
      and noncoding-site nucleotide substitution rate analyses of these two Volvox
      ptDNAs suggest that there are drastically different plastid mutation rates
      operating in the coding versus intergenic regions, supporting the idea that error
      prone DNA repair in repeat-rich intergenic spacers is contributing to genome
      expansion. Our results reinforce the idea that the volvocine line harbors
      extremes in plastome size but ultimately shed doubt on some of the previously
      proposed hypotheses for ptDNA inflation within the lineage.

PMID- 30102349
TI  - On Entropy and Information in Gene Interaction Networks.
AB  - Motivation: Modern biological experiments often produce candidate lists of genes
      presumably related to the studied phenotype. One can ask if the gene list as a
      whole makes sense in the context of existing knowledge: Are the genes in the list
      reasonably related to each other or do they look like a random assembly? There
      are also situations when one wants to know if two or more gene sets are closely
      related. Gene enrichment tests based on counting the number of genes two sets
      have in common are adequate if we presume that two genes are related only when
      they are in fact identical. If by related we mean well connected in the
      interaction network space, we need a new measure of relatedness for gene sets.
      Results: We derive entropy, interaction information and mutual information for
      gene sets on interaction networks, starting from a simple phenomenological model
      of a living cell. Formally, the model describes a set of interacting linear
      harmonic oscillators in thermal equilibrium. Because the energy function is a
      quadratic form of the degrees of freedom, entropy and all other derived
      information quantities can be calculated exactly. We apply these concepts to
      estimate the probability that genes from several independent genome-wide
      association studies are not mutually informative; to estimate the probability
      that two disjoint canonical metabolic pathways are not mutually informative; and
      to infer relationships among human diseases based on their gene signatures. We
      show that the present approach is able to predict observationally validated
      relationships not detectable by gene enrichment methods. The converse is also
      true; the two methods are therefore complementary. Availability: The functions
      defined in this paper are available in an R package, gsia, available for download
      at https://github.com/ucsd-ccbb/gsia. Supplementary information: Supplementary
      data are available at Bioinformatics online.

PMID- 30102348
TI  - Transposable Elements Contribute to the Adaptation of Arabidopsis thaliana.
AB  - Transposable elements (TEs) are mobile genetic elements with very high mutation
      rates that play important roles in shaping genome architecture and regulating
      phenotypic variation. However, the extent to which TEs influence the adaptation
      of organisms in their natural habitats is largely unknown. Here, we scanned 201
      representative resequenced genomes from the model plant Arabidopsis thaliana and
      identified 2,311 polymorphic TEs from noncentromeric regions. We found expansion
      and contraction of different types of TEs in different A. thaliana populations.
      More importantly, we identified two TE insertions that are likely candidates to
      play a role in adaptive evolution. Our results highlight the importance of
      variations in TEs for the adaptation of plants in general in the context of rapid
      global climate change.

PMID- 30102351
TI  - Recrudescence, reinfection or relapse? A more rigorous framework to assess
      chloroquine efficacy for vivax malaria.
AB  - Background: Plasmodium vivax resistance to chloroquine has been reported
      worldwide, although the WHO clinical drug efficacy studies protocol does not
      allow to classify patient outcomes. Methods: We enrolled 40 vivax malaria
      patients in northeastern Cambodia, where >17% treatment failures were previously
      reported. Patients were treated with chloroquine (30mg/kg) and followed for two
      months, with frequent clinical examination and capillary blood sample collection
      for microscopy, molecular parasite detection and genotyping, and drug
      concentration measurements. Reinfections were prevented by relocating patients to
      a transmission-free area. Results: P. vivax parasites were eliminated in all
      patients by day3. Genomic analyses revealed that all clones in polyclonal
      infections were cleared at the same rate, indicating their equal susceptibility
      to CQ. Chloroquine blood concentration were below the therapeutic level in all
      recurrent infections (24/40 patients), which were efficiently cleared by a second
      course of chloroquine treatment. Whole genome sequencing indicated that two-third
      (6/8) of the recurrent parasites resulted from heterologous relapses whose 50%
      are from by sibling/recombinant clones. Conclusions: No evidence of chloroquine
      resistance were observed. Our data suggest that P. vivax antimalarial drug
      resistance is likely overestimated and that the current guidelines for clinical
      drug studies in vivax malaria need to be revised.

PMID- 30102350
TI  - Convergent Evolution among Ruminant-Pathogenic Mycoplasma Involved Extensive Gene
      Content Changes.
AB  - Convergent evolution, a process by which organisms evolved independently to have
      similar traits, provides opportunities to understand adaptation. The bacterial
      genus Mycoplasma contains multiple species that evolved independently to become
      ruminant pathogens, which represents an interesting study system for
      investigating the process. In this work, we determined the genome sequences of 11
      Entomoplasma/Mesoplasma species. This new data set, together with the other
      available Mollicutes genomes, provided comprehensive taxon sampling for inferring
      the gene content evolution that led to the emergence of Mycoplasma Mycoides
      cluster. Our results indicated that the most recent common ancestor (MRCA) of the
      Mycoides-Entomoplasmataceae clade lost ~15% of the core genes when it diverged
      from the Spiroplasma Apis clade. After this initial wave of genome reduction,
      relatively few gene gains or losses were inferred until the emergence of the
      Mycoides cluster. Compared with those Entomoplasmataceae lineages that maintained
      the association with insects, the MRCA of the Mycoides cluster experienced a
      second wave of gene losses, as well as acquiring >100 novel genes through
      horizontal gene transfer. These gene acquisitions involved many with the
      Mycoplasma Hominis/Pneumoniae lineages as the putative donors, suggesting that
      gene exchanges among these vertebrate symbionts with distinct phylogenetic
      affiliations may be important in the emergence of the Mycoides cluster. These
      findings demonstrated that the gene content of bacterial genomes could be
      exceedingly dynamic, even for those symbionts with highly reduced genomes.
      Moreover, the emergence of novel pathogens may involve extensive remodeling of
      gene content, rather than acquisition of few virulence genes.

PMID- 30102352
TI  - Growth performance, organ weights, and blood parameters of nursery pigs fed diets
      containing increasing levels of cold-pressed canola cake.
AB  - Oilseed cakes have high oil content, and thus their inclusion in swine can lead
      to reduced dietary inclusion of oil, and hence reduced cost of feed. An
      experiment was conducted to determine effects of including Brassica napus-derived
      cold-pressed canola cake (CPCC) in diets for nursery pigs on growth performance,
      organ weights relative to live body weight (BW), and blood parameters. A total of
      160 pigs (initial BW: 7.8 +/- 0.9 kg), which had been weaned at 21 d of age were
      housed in 40 pens (4 pigs/pen) and fed 4 diets (10 pens/diet) in a randomized
      complete block design for 35 d. The 4 diets were corn-soybean meal (SBM)-based
      basal diet and the basal diet with corn and SBM replaced by 20, 30, or 40% of
      CPCC. The diets were fed in 2 phases, Phase 1 from day 0 to 14 and Phase 2 from
      day 14 to 35; and were formulated to meet NRC (2012) nutrient recommendations for
      nursery pigs and to have the same net energy, standardized ileal digestible amino
      acid, and digestible P contents. Increasing inclusion of CPCC in diets was
      achieved by partial replacement of corn, SBM, limestone, and mono-calcium
      phosphate. Growth performance was determined by phase. On day 35, 1 pig from each
      pen was euthanized for determining organ weights and blood parameters. The CPCC
      contained 7.63% moisture, and on a dry matter basis, it (CPCC) contained 39.6%
      crude protein, 2.32% Lys, 0.74% Met, 1.63% Thr, 0.50% Trp, 16.0% ether extract,
      20.7% neutral detergent fiber, and 14.9 umol/g of glucosinolates. Increasing
      dietary CPCC from 0 to 40% linearly reduced (P < 0.05) overall (day 0 to 35)
      average daily gain and average daily feed intake (0.440 to 0.288 kg/d and 0.739
      to 0.522 kg/d, respectively). Increasing dietary CPCC from 0 to 40% resulted in a
      linear increase (P < 0.05) in liver weight by 0.1 g/kg of BW and in thyroid gland
      weight by 2.2 mg/kg of BW, but in a linear reduction (P < 0.05) in serum
      tetraiodothyronine (T4) level by 0.2 ng/mL for each 1% increase in CPCC at 35 d
      of age. No differences were observed in heart and kidney weights relative to live
      BW, and in serum triiodothyronine (T3) concentration. In conclusion, increasing
      dietary CPCC from 0 to 40% by reducing corn and SBM levels resulted in depressed
      growth performance, increased metabolic activity in liver and thyroid gland, and
      reduced serum T4 level of pigs. Thus, the amounts of CPCC included in nursery pig
      diets should be based on targeted growth performance and cost of other feedstuffs
      in relation to that of CPCC.

PMID- 30102353
TI  - Ergot alkaloids induce vasoconstriction of bovine uterine and ovarian blood
      vessels.
AB  - Fescue toxicosis is a syndrome that impairs growth and reproduction in cattle
      grazing endophyte-infected tall fescue [Lolium arundinaceum [(Schreb.].)
      Darbysh)] in the United States, resulting in approximately $1 billion in annual
      economic loss in species that utilize this forage resource. Approximately 90% of
      tall fescue contains an endophytic fungus (Epichloe coenophiala) that produces
      ergot alkaloids. Ergot alkaloids cause vasoconstriction and reduced blood flow to
      the extremities; however, it remains unknown how blood flow to the reproductive
      organs is affected in cattle. Therefore, the objective of this study was to
      determine if ergot alkaloids from endophyte-infected tall fescue reduce blood
      flow to the reproductive organs, thus hindering reproductive function. Angus
      heifers (n = 36) naive to ergot alkaloids were placed in Calan gates and randomly
      assigned to receive either endophyte-infected fescue seed (E+) or noninfected
      fescue seed (E-; control) in a total mixed ration for 63 d. Weekly measurements
      were taken to monitor heifer growth and response to ergot alkaloid exposure.
      Reproductive measurements, including ovarian structures, uterine and ovarian
      vessel diameter, and hormone concentrations were determined after heifers were
      synchronized using the standard CO-Synch + 7 d CIDR protocol to ensure all
      measurements were collected at the same stages of the estrous cycle (0, 4, 10,
      and 17 d). Data were analyzed using repeated measures in PROC MIXED of SAS.
      Average daily gain was decreased for the E+ group (0.8 kg/d) compared to control
      heifers (1.0 kg/d). Body condition scores tended to be greater in control heifers
      compared to the E+ group (P = 0.053). Additionally, hair coat and hair shedding
      scores were greater in E+ heifers compared to controls (P < 0.05). Heart rate,
      rectal temperature, respiration rate, and blood pressure did not differ between
      treatments (P > 0.05). Vasoconstriction was observed in the caudal artery, but
      not the caudal vein, in heifers consuming the E+ fescue seed (P < 0.05). No
      differences were observed in antral follicle counts, corpus luteum area or
      circulating progesterone concentrations in E+ heifers compared to controls (P >
      0.05). There was a significant decrease in the diameter of arteries and veins
      servicing the ovary and uterus on day 10 and 17 of the estrous cycle. Reduction
      in blood flow to the reproductive organs during critical times in the estrous
      cycle may contribute to the reduced ovarian function and pregnancy rates
      associated with fescue toxicosis.

PMID- 30102354
TI  - Excellent durability of homografts in pulmonary position analysed in a predefined
      adult group with tetralogy of Fallot.
AB  - OBJECTIVES: In repaired tetralogy of Fallot, surgical pulmonary valve replacement
      (PVR) is in certain cases required. Our institution reported earlier about 26
      patients who received a pulmonary homograft via PVR. To date, we have data from
      more than 17 years of follow-up. The aim of this retrospective study was to
      evaluate the late haemodynamic and clinical outcomes in this predefined patient
      group. METHODS: Between 1993 and 2001, 26 patients underwent PVR for pulmonary
      regurgitation (58% men; 30.4 +/- 8.9 years). The rates of mortality and of
      complications (re-PVR, ablation and cardioverter defibrillator implants) were
      analysed. Other main study outcomes were haemodynamic parameters determined from
      cardiovascular magnetic resonance imaging: pulmonary regurgitation; right
      ventricular (RV) end-diastolic volume; RV ejection fraction; left ventricular
      (LV) end-diastolic volume; LV ejection fraction; New York Heart Association
      functional class at the latest follow-up visit; and echocardiographic parameters
      of the right ventricle. RESULTS: The median follow-up time was 17 +/- 1.1 years.
      Overall freedom from complications was 61.5% (95% confidence interval 47.5
      78.6%). One patient died 18 months after surgery of unknown causes. Two patients
      needed replacement of the homograft at 24 and 39 months after PVR. The indication
      in both patients was recurrence of severe homograft regurgitation with important
      RV dilatation. Six patients received an implantable cardioverter defibrillator at
      a median age of 41 years (interquartile range 36-47); 12 patients experienced
      supra- and/or ventricular arrhythmias and 6 of these needed ablation. There was
      no significant deterioration of haemodynamic function or functional class.
      CONCLUSIONS: The patients who underwent PVR exhibited long-term follow-up
      stabilization of RV function and impressive functional durability of the graft.
      After a follow-up of 17 years, 23 out of 26 patients (89%) were alive without
      redo PVR. Event-free survival was good (61.5%).

PMID- 30102355
TI  - Hepatitis C virus escape studies for human monoclonal antibody AR4A reveal
      isolate-specific resistance and a high barrier to resistance.
AB  - Global control of hepatitis C virus (HCV) depends on development of a
      prophylactic vaccine. We studied escape for cross-genotype-reactive neutralizing
      antibody AR4A, providing valuable information for HCV vaccine design. We cultured
      HCV Core-NS2 recombinants H77(genotype 1a)/JFH1 or the highly-antibody-sensitive
      hypervariable region 1 (HVR1)-deleted variants H77/JFH1?HVR1 and J6(genotype
      2a)/JFH1?HVR1 in Huh7.5 cells with AR4A. Long-term AR4A exposure of H77/JFH1 and
      H77/JFH1?HVR1 did not yield resistance. However, J6/JFH1?HVR1 developed the
      envelope-E2 substitutions I696T or I696N, which reduced AR4A binding
      (I696N>I696T). I696N conferred greater AR4A-resistance than I696T in
      J6/JFH1?HVR1, whereas the reverse was observed in J6/JFH1. This was because
      I696N, but not I696T, conferred broadly increased antibody neutralization
      sensitivity to J6/JFH1. I696N and I696T abrogated infectivity of H77/JFH1 and
      broadly increased neutralization sensitivity of S52(genotype 3a)/JFH1. In
      conclusion, I696 is in the AR4A epitope, which has a high barrier to resistance,
      thus strengthening the rationale for its inclusion in rational HCV vaccine
      designs.

PMID- 30102356
TI  - Testosterone plays a permissive role in angiotensin II-induced hypertension and
      cardiac hypertrophy in male rats.
AB  - Sex hormone-dependent vascular reactivity is an underlying factor contributing to
      sex differences in blood pressure. Inappropriate activation of the renin
      angiotensin system (RAS) is involved in vascular dysfunction and hypertension.
      This study evaluated the role of androgens (testosterone) in angiotensin II (Ang
      II) -induced increase in blood pressure, vascular reactivity and cardiac
      hypertrophy. Eight weeks-old male Wistar rats underwent sham operation,
      castration, or castration with testosterone replacement. After 12 weeks of
      chronic changes in androgen status, Ang II (120 ng/kg per minute) or saline was
      infused for 28 days via subcutaneous miniosmotic pump, and changes in blood
      pressure was measured. Vascular reactivity and Ang II receptor levels were
      examined in mesenteric arteries. Heart weight, cardiac ANP mRNA levels and
      fibrosis were also assessed. Ang II infusion increased arterial pressure in
      intact males. The Ang II-induced increase in hypertensive response was prevented
      in castrated males. Testosterone replacement in castrated males restored Ang II
      induced hypertensive responses. Castration reduced vascular AT1R/AT2R ratio, an
      effect that was reversed by testosterone replacement. Ang II-induced hypertension
      was associated with increased contractile response of mesenteric arteries to Ang
      II and phenylephrine in intact and testosterone-replaced castrated males; these
      increases were prevented in castrated males. Ang II infusion induced increased
      left ventricle-to-body weight ratio and ANP mRNA expression, indicators of left
      ventricular hypertrophy, and fibrosis in intact and testosterone-replaced
      castrated males, and castration prevented the increase in these parameters caused
      by Ang II. This study demonstrate that testosterone plays a permissive role in
      development and maintenance of Ang II-induced vascular dysfunction, hypertension
      and cardiac hypertrophy.

PMID- 30102359
TI  - The Right to Trans-Specific Healthcare in Norway: Understanding the Health Needs
      of Transgender People.
AB  - Human rights discourse on the rights of transgender people has to a large extent
      focused on access to correction of legal gender and medical preconditions for
      this change. Jurisdictions across the world are now beginning to free legal
      gender recognition from medical interventions and examinations. State bodies
      have, however, done little to realise the rights of transgender people to
      adequate healthcare. A key issue is whether international law obliges states to
      ensure access to trans-specific healthcare. This article examines the right to
      healthcare appropriate to transgender persons' needs. Drawing on in-depth
      interviews with transgender people living in Norway, it investigates how
      individuals explain their needs for trans-specific healthcare. It shows that
      Norwegian healthcare practice uses the diagnosis of 'transsexualism' to determine
      a person's needs for trans-specific healthcare and as such excludes many from
      receiving the healthcare they need. The article analyses whether trans-specific
      healthcare falls within the ambit of the right to health under Article 12 of the
      International Covenant on Economic, Social and Cultural Rights (ICESCR), and the
      right to necessary healthcare under the Norwegian Patients' Rights Act. It
      concludes that the Norwegian authorities are obliged to provide equal access to
      adequate trans-specific healthcare to those who need it.

PMID- 30102357
TI  - Xenacoelomorpha Survey Reveals That All 11 Animal Homeobox Gene Classes Were
      Present in the First Bilaterians.
AB  - Homeodomain transcription factors are involved in many developmental processes
      across animals and have been linked to body plan evolution. Detailed
      classifications of these proteins identified 11 distinct classes of homeodomain
      proteins in animal genomes, each harboring specific sequence composition and
      protein domains. Although humans contain the full set of classes, Drosophila
      melanogaster and Caenorhabditis elegans each lack one specific class.
      Furthermore, representative previous analyses in sponges, ctenophores, and
      cnidarians could not identify several classes in those nonbilaterian metazoan
      taxa. Consequently, it is currently unknown when certain homeodomain protein
      classes first evolved during animal evolution. Here, we investigate
      representatives of the sister group to all remaining bilaterians, the
      Xenacoelomorpha. We analyzed three acoel, one nemertodermatid, and one
      Xenoturbella transcriptomes and identified their expressed homeodomain protein
      content. We report the identification of representatives of all 11 classes of
      animal homeodomain transcription factors in Xenacoelomorpha and we describe and
      classify their homeobox genes relative to the established animal homeodomain
      protein families. Our findings suggest that the genome of the last common
      ancestor of bilateria contained the full set of these gene classes, supporting
      the subsequent diversification of bilaterians.

PMID- 30102358
TI  - VIRESCENT-ALBINO LEAF 1 regulates leaf colour development and cell division in
      rice.
AB  - The de novo synthesis of purine nucleotides is crucial to all living organisms,
      but limited information is available for plants. In this study, we isolated a
      virescent-albino leaf 1 (val1) mutant of rice (Oryza sativa) that produces
      dynamic green-revertible albino and narrow-leaf phenotypes. In albino leaves,
      chloroplast development was defective, pigment contents were reduced, and cell
      division was impaired compared with the wild-type. Map-based cloning revealed
      that VAL1 encodes a phosphoribosylamine-glycine ligase (PurD), the second enzyme
      in the de novo purine biosynthesis pathway. Subcellular localization analysis
      demonstrated that VAL1 was localized in the chloroplast. Our results demonstrate
      that VAL1 is a crucial enzyme in the de novo purine biosynthesis pathway and is
      involved in regulating chloroplast development, chlorophyll metabolism, and cell
      division during leaf development in rice.

PMID- 30102360
TI  - Elimination through collaboration: success factors in a global consortium.
AB  - The Global Trachoma Mapping Project (GTMP) is the largest infectious disease
      survey ever undertaken. With 60 partners, 2.6 million people were examined across
      29 countries for the blinding neglected tropical disease (NTD) trachoma,
      establishing the prevalence of the disease globally. Such an achievement was only
      made possible by building a diverse worldwide consortium. This article examines
      that public-private consortium and attempts to highlight key factors in the
      success of its development and operation. Two critical factors in the project's
      success were the establishment of an evidence-based common approach and urgency
      around a shared goal. The common approach (the GTMP methodologies, tools and
      training approach) and the goal (GET2020 through the SAFE strategy) are
      thoroughly detailed in this article. Transparency at all levels; clear roles for
      committees, partners, agencies and ministries of health and shared funding played
      important roles and are explored here. It is hoped that by examining and sharing
      the positive factors leading to the establishment and work of this specific
      consortium, other similar initiatives-for NTDs, for health more broadly and for
      other development areas-will be able to adopt such an approach for effective
      collaboration.

PMID- 30102361
TI  - Producing proT cells to promote immunotherapies.
AB  - T lymphocytes are critical mediators of the adaptive immune system and they can
      be harnessed as therapeutic agents against pathogens and in cancer immunotherapy.
      T cells can be isolated and expanded from patients and potentially generated in
      vitro using clinically relevant systems. An ultimate goal for T-cell
      immunotherapy is to establish a safe, universal effector cell type capable of
      transcending allogeneic and histocompatibility barriers. To this end, human
      pluripotent stem cells offer an advantage in generating a boundless supply of T
      cells that can be readily genetically engineered. Here, we review emerging T-cell
      therapeutics, including tumor-infiltrating lymphocytes, chimeric antigen
      receptors and progenitor T cells (proT cells) as well as feeder cell-free in
      vitro systems for their generation. Furthermore, we explore their potential for
      adoption in the clinic and highlight the challenges that must be addressed to
      increase the therapeutic success of a universal immunotherapy.

PMID- 30102364
TI  - A Single-Nucleotide Polymorphism Upstream of the HLA-C Locus Is Associated With
      an Anti-Hepatitis C Virus-Seronegative State in a High-Risk Exposed Cohort.
AB  - In this study, we examined the impact of the rs9264942 single-nucleotide
      polymorphism, previously shown to be associated with human immunodeficiency virus
      infection status and HLA-C expression, on the hepatitis C virus status in 359
      people who inject drugs (PWID). The linkage of rs9264942 alleles to HLA-C
      antigens assigned to different expression levels was confirmed. Multivariate
      analysis revealed the age (P = .003) and the rs9264942 genotype (P = .006) to be
      independent factors for the classification to the PWID groups. Our study showed
      that the presence of the rs9264942 C/C genotype was associated with persistent
      seronegativity.

PMID- 30102363
TI  - Coalescent Analysis of Phylogenomic Data Confidently Resolves the Species
      Relationships in the Anopheles gambiae Species Complex.
AB  - Deep coalescence and introgression make it challenging to infer phylogenetic
      relationships among closely related species that arose through radiative
      speciation events. Despite numerous phylogenetic analyses and the availability of
      whole genomes, the phylogeny in the Anopheles gambiae species complex has not
      been confidently resolved. Here we extract over 80, 000 coding and noncoding
      short segments (called loci) from the genomes of six members of the species
      complex and use a Bayesian method under the multispecies coalescent model to
      infer the species tree, which takes into account genealogical heterogeneity
      across the genome and uncertainty in the gene trees. We obtained a robust
      estimate of the species tree from the distal region of the X chromosome: (A.
      merus, ((A. melas, (A. arabiensis, A. quadriannulatus)), (A. gambiae, A.
      coluzzii))), with A. merus to be the earliest branching species. This species
      tree agrees with the chromosome inversion phylogeny and provides a parsimonious
      interpretation of inversion and introgression events. Simulation informed by the
      real data suggest that the coalescent approach is reliable while the sliding
      window analysis used in a previous phylogenomic study generates artifactual
      species trees. Likelihood ratio test of gene flow revealed strong evidence of
      autosomal introgression from A. arabiensis into A. gambiae (at the average rate
      of ~0.2 migrants per generation), but not in the opposite direction, and
      introgression of the 3 L chromosomal region from A. merus into A.
      quadriannulatus. Our results highlight the importance of accommodating incomplete
      lineage sorting and introgression in phylogenomic analyses of species that arose
      through recent radiative speciation events.

PMID- 30102365
TI  - Integrative Population and Physiological Genomics Reveals Mechanisms of
      Adaptation in Killifish.
AB  - Adaptive divergence between marine and freshwater (FW) environments is important
      in generating phyletic diversity within fishes, but the genetic basis of this
      process remains poorly understood. Genome selection scans can identify adaptive
      loci, but incomplete knowledge of genotype-phenotype connections makes
      interpreting their significance difficult. In contrast, association mapping
      (genome-wide association mapping [GWAS], random forest [RF] analyses) links
      genotype to phenotype, but offer limited insight into the evolutionary forces
      shaping variation. Here, we combined GWAS, RF, and selection scans to identify
      loci important in adaptation to FW environments. We utilized FW-native and
      brackish water (BW)-native populations of Atlantic killifish (Fundulus
      heteroclitus) as well as a naturally admixed population between the two. We
      measured morphology and multiple physiological traits that differ between
      populations and may contribute to osmotic adaptation (salinity tolerance, hypoxia
      tolerance, metabolic rate, body shape) and used a reduced representation approach
      for genome-wide genotyping. Our results show patterns of population divergence in
      physiological capabilities that are consistent with local adaptation. Population
      genomic scans between BW-native and FW-native populations identified genomic
      regions evolving by natural selection, whereas association mapping revealed loci
      that contribute to variation for each trait. There was substantial overlap in the
      genomic regions putatively under selection and loci associated with phenotypic
      traits, particularly for salinity tolerance, suggesting that these regions and
      genes are important for adaptive divergence between BW and FW environments.
      Together, these data provide insight into the mechanisms that enable
      diversification of fishes across osmotic boundaries.

PMID- 30102362
TI  - Protein encoded in human telomerase RNA is involved in cell protective pathways.
AB  - Several studies have described functional peptides encoded in RNA that are
      considered to be noncoding. Telomerase RNA together with telomerase reverse
      transcriptase and regulatory proteins make up the telomerase complex, the major
      component of the telomere length-maintaining machinery. In contrast to protein
      subunits, telomerase RNA is expressed constitutively in most somatic cells where
      telomerase reverse transcriptase is absent. We show here that the transcript of
      human telomerase RNA codes a 121 amino acid protein (hTERP). The existence of
      hTERP was shown by immunoblotting, immunofluorescence microscopy and mass
      spectroscopy. Gain-of-function and loss-of-function experiments showed that hTERP
      protects cells from drug-induced apoptosis and participates in the processing of
      autophagosome. We suggest that hTERP regulates crosstalk between autophagy and
      apoptosis and is involved in cellular adaptation under stress conditions.

PMID- 30102366
TI  - Computational resources associating diseases with genotypes, phenotypes and
      exposures.
AB  - The causes of a disease and its therapies are not only related to genotypes, but
      also associated with other factors, including phenotypes, environmental
      exposures, drugs and chemical molecules. Distinguishing disease-related factors
      from many neutral factors is critical as well as difficult. Over the past two
      decades, bioinformaticians have developed many computational resources to
      integrate the omics data and discover associations among these factors. However,
      researchers and clinicians are experiencing difficulties in choosing appropriate
      resources from hundreds of relevant databases and software tools. Here, in order
      to assist the researchers and clinicians, we systematically review the public
      computational resources of human diseases related to genotypes, phenotypes,
      environment factors, drugs and chemical exposures. We briefly describe the
      development history of these computational resources, followed by the details of
      the relevant databases and software tools. We finally conclude with a discussion
      of current challenges and future opportunities as well as prospects on this
      topic.

PMID- 30102367
TI  - Review and comparative assessment of similarity-based methods for prediction of
      drug-protein interactions in the druggable human proteome.
AB  - Drug-protein interactions (DPIs) underlie the desired therapeutic actions and the
      adverse side effects of a significant majority of drugs. Computational prediction
      of DPIs facilitates research in drug discovery, characterization and repurposing.
      Similarity-based methods that do not require knowledge of protein structures are
      particularly suitable for druggable genome-wide predictions of DPIs. We review 35
      high-impact similarity-based predictors that were published in the past decade.
      We group them based on three types of similarities and their combinations that
      they use. We discuss and compare key aspects of these methods including source
      databases, internal databases and their predictive models. Using our novel
      benchmark database, we perform comparative empirical analysis of predictive
      performance of seven types of representative predictors that utilize each type of
      similarity individually and all possible combinations of similarities. We assess
      predictive quality at the database-wide DPI level and we are the first to also
      include evaluation over individual drugs. Our comprehensive analysis shows that
      predictors that use more similarity types outperform methods that employ fewer
      similarities, and that the model combining all three types of similarities
      secures area under the receiver operating characteristic curve of 0.93. We offer
      a comprehensive analysis of sensitivity of predictive performance to intrinsic
      and extrinsic characteristics of the considered predictors. We find that
      predictive performance is sensitive to low levels of similarities between
      sequences of the drug targets and several extrinsic properties of the input drug
      structures, drug profiles and drug targets. The benchmark database and a
      webserver for the seven predictors are freely available at
      http://biomine.cs.vcu.edu/servers/CONNECTOR/.

PMID- 30102368
TI  - CellBIC: bimodality-based top-down clustering of single-cell RNA sequencing data
      reveals hierarchical structure of the cell type.
AB  - Single-cell RNA sequencing (scRNA-seq) is a powerful tool to study heterogeneity
      and dynamic changes in cell populations. Clustering scRNA-seq is essential in
      identifying new cell types and studying their characteristics. We develop CellBIC
      (single Cell BImodal Clustering) to cluster scRNA-seq data based on modality in
      the gene expression distribution. Compared with classical bottom-up approaches
      that rely on a distance metric, CellBIC performs hierarchical clustering in a top
      down manner. CellBIC outperformed the bottom-up hierarchical clustering approach
      and other recently developed clustering algorithms while maintaining the
      hierarchical structure of cells. Importantly, CellBIC identifies type 2 diabetes
      and age specific beta cell signatures characterized by SIX3 and CDH2,
      respectively.

PMID- 30102369
TI  - Sow stress levels and behavior and piglet performances in farrowing crates and
      farrowing pens with temporary crating.
AB  - Farrowing pens with temporary crating have been developed as a compromise between
      conventional farrowing crates and pens to better accommodate the welfare of both
      sow and piglets during lactation. However, not much is known about the behavioral
      and physiological consequences of early removal of confinement on the sow and
      piglets during lactation. The aim of this study was to assess the effects on sow
      and piglet performance of temporary crating until 3-d postpartum at 2 times
      points, immediately after confinement removal and 25 d into lactation. Sows were
      crated from 5-d prepartum either to weaning (permanently crated-PC group; N =14)
      or to D3 (83.0 +/- 1.3 h) postpartum (Temporarily crated - TC group N = 13). Sow
      postural changes, activity, cortisol and IgA concentrations, and piglet body
      weight gain and behavior were assessed on D4 and on D25 postpartum, whereas
      piglet mortality was assessed throughout lactation. Data were analyzed using PROC
      GLM and PROC GENMOD of SAS. On D4 postfarrowing, TC sows were more active (10.9%
      vs. 7.1%; SEM: 0.8; P = 0.002), rolled more frequently (21.3% vs. 14.4%; SEM:
      1.6; P = 0.008), and had lower IgA concentrations (139.7 vs. 75.2 ug/mL; SEM:
      20.3; P = 0.040) than PC sows. No effects of housing were found (P > 0.05) on
      standing-to-lying movement or cortisol concentrations. No differences for any
      variables were found (P > 0.05) on D25. Mortality, body weights, and activity
      levels at the udder or in the pen of pigs born to PC sows did not differ (P >
      0.05) from those of piglets born to TC sows on D4 nor on D25. This study
      indicates that removal of confinement on the 4th-d postpartum may have had small
      short-term positive effects on sow behavior and stress levels (as measured by
      IgA), and that it did not impair piglets' behavior and performance during
      lactation. Therefore, this work suggests that temporary crating limited to the
      first 3-d postpartum might be a feasible alternative to improve welfare under
      intensive production conditions.

PMID- 30102370
TI  - A two-nuclease pathway involving RNase H1 is required for primer removal at human
      mitochondrial OriL.
AB  - The role of Ribonuclease H1 (RNase H1) during primer removal and ligation at the
      mitochondrial origin of light-strand DNA synthesis (OriL) is a key, yet poorly
      understood, step in mitochondrial DNA maintenance. Here, we reconstitute the
      replication cycle of L-strand synthesis in vitro using recombinant mitochondrial
      proteins and model OriL substrates. The process begins with initiation of DNA
      replication at OriL and ends with primer removal and ligation. We find that RNase
      H1 partially removes the primer, leaving behind the last one to three
      ribonucleotides. These 5'-end ribonucleotides disturb ligation, a conclusion
      which is supported by analysis of RNase H1-deficient patient cells. A second
      nuclease is therefore required to remove the last ribonucleotides and we
      demonstrate that Flap endonuclease 1 (FEN1) can execute this function in vitro.
      Removal of RNA primers at OriL thus depends on a two-nuclease model, which in
      addition to RNase H1 requires FEN1 or a FEN1-like activity. These findings define
      the role of RNase H1 at OriL and help to explain the pathogenic consequences of
      disease causing mutations in RNase H1.

PMID- 30102371
TI  - Identification of clustered organellar short (cos) RNAs and of a conserved family
      of organellar RNA-binding proteins, the heptatricopeptide repeat proteins, in the
      malaria parasite.
AB  - Gene expression in mitochondria of Plasmodium falciparum is essential for
      parasite survival. The molecular mechanisms of Plasmodium organellar gene
      expression remain poorly understood. This includes the enigmatic assembly of the
      mitochondrial ribosome from highly fragmented rRNAs. Here, we present the
      identification of clustered organellar short RNA fragments (cosRNAs) that are
      possible footprints of RNA-binding proteins (RBPs) in Plasmodium organelles. In
      plants, RBPs of the pentatricopeptide repeat (PPR) class produce footprints as a
      consequence of their function in processing organellar RNAs. Intriguingly, many
      of the Plasmodium cosRNAs overlap with 5'-ends of rRNA fragments. We hypothesize
      that these are footprints of RBPs involved in assembling the rRNA fragments into
      a functioning ribosome. A bioinformatics search of the Plasmodium nuclear genome
      identified a hitherto unrecognized organellar helical-hairpin-repeat protein
      family that we term heptatricopeptide repeat (HPR) proteins. We demonstrate that
      selected HPR proteins are targeted to mitochondria in P. berghei and that one of
      them, PbHPR1, associates with RNA, but not DNA in vitro. A phylogenetic search
      identified HPR proteins in a wide variety of eukaryotes. We hypothesize that HPR
      proteins are required for processing and stabilizing RNAs in Apicomplexa and
      other taxa.

PMID- 30102373
TI  - EVI1 carboxy-terminal phosphorylation is ATM-mediated and sustains
      transcriptional modulation and self-renewal via enhanced CtBP1 association.

PMID- 30102374
TI  - Comprehensive comparative analysis of methods and software for identifying viral
      integrations.
AB  - Many viruses are capable of integrating in the human genome, particularly viruses
      involved in tumorigenesis. Viral integrations can be considered genetic markers
      for discovering virus-caused cancers and inferring cancer cell development. Next
      generation sequencing (NGS) technologies have been widely used to screen for
      viral integrations in cancer genomes, and a number of bioinformatics tools have
      been developed to detect viral integrations using NGS data. However, there has
      been no systematic comparison of the methods or software. In this study, we
      performed a comprehensive comparative analysis of the designs, performance,
      functionality and limitations among the existing methods and software for
      detecting viral integrations. We further compared the sensitivity, precision and
      runtime of integration detection of four representative tools. Our analyses
      showed that each of the existing software had its own merits; however, none of
      them were sufficient for parallel or accurate virome-wide detection. After
      carefully evaluating the limitations shared by the existing methods, we proposed
      strategies and directions for developing virome-wide integration detection.

PMID- 30102372
TI  - Displacement of the transcription factor B reader domain during transcription
      initiation.
AB  - Transcription initiation by archaeal RNA polymerase (RNAP) and eukaryotic RNAP II
      requires the general transcription factor (TF) B/ IIB. Structural analyses of
      eukaryotic transcription initiation complexes locate the B-reader domain of TFIIB
      in close proximity to the active site of RNAP II. Here, we present the first
      crosslinking mapping data that describe the dynamic transitions of an archaeal
      TFB to provide evidence for structural rearrangements within the transcription
      complex during transition from initiation to early elongation phase of
      transcription. Using a highly specific UV-inducible crosslinking system based on
      the unnatural amino acid para-benzoyl-phenylalanine allowed us to analyze
      contacts of the Pyrococcus furiosus TFB B-reader domain with site-specific
      radiolabeled DNA templates in preinitiation and initially transcribing complexes.
      Crosslink reactions at different initiation steps demonstrate interactions of TFB
      with DNA at registers +6 to +14, and reduced contacts at +15, with structural
      transitions of the B-reader domain detected at register +10. Our data suggest
      that the B-reader domain of TFB interacts with nascent RNA at register +6 and +8
      and it is displaced from the transcribed-strand during the transition from +9 to
      +10, followed by the collapse of the transcription bubble and release of TFB from
      register +15 onwards.

PMID- 30102376
TI  - Readiness for Responding to a Severe Pandemic 100 Years After 1918.
AB  - The 1918 H1N1 pandemic caused an unprecedented number of deaths worldwide. The
      tools to deal with the global emergency were limited; there were insufficient
      surveillance systems and a dearth of diagnostic, treatment, and prevention
      options. With continuing focus on pandemic planning, technologic advances in
      surveillance, vaccine capabilities, and 21st century medical care and
      countermeasures, we are more prepared for a severe pandemic than people were 100
      years ago; however, notable gaps remain.

PMID- 30102375
TI  - MIR100 host gene-encoded lncRNAs regulate cell cycle by modulating the
      interaction between HuR and its target mRNAs.
AB  - Long non-coding RNAs (lncRNAs) regulate vital biological processes, including
      cell proliferation, differentiation and development. A subclass of lncRNAs is
      synthesized from microRNA (miRNA) host genes (MIRHGs) due to pre-miRNA
      processing, and are categorized as miRNA-host gene lncRNAs (lnc-miRHGs).
      Presently, the cellular function of most lnc-miRHGs is not well understood. We
      demonstrate a miRNA-independent role for a nuclear-enriched lnc-miRHG in cell
      cycle progression. MIR100HG produces spliced and stable lncRNAs that display
      elevated levels during the G1 phase of the cell cycle. Depletion of MIR100HG
      encoded lncRNAs in human cells results in aberrant cell cycle progression without
      altering the levels of miRNA encoded within MIR100HG. Notably, MIR100HG interacts
      with HuR/ELAVL1 as well as with several HuR-target mRNAs. Further, MIR100HG
      depleted cells show reduced interaction between HuR and three of its target
      mRNAs, indicating that MIR100HG facilitates interaction between HuR and target
      mRNAs. Our studies have unearthed novel roles played by a MIRHG-encoded lncRNA in
      regulating RNA binding protein activity, thereby underscoring the importance of
      determining the function of several hundreds of lnc-miRHGs that are present in
      human genome.

PMID- 30102377
TI  - Effects of dietary pectin on the profile and transport of intestinal bile acids
      in young pigs.
AB  - Pectin has been known to lower circulating cholesterol by interacting with bile
      acid (BA) metabolism. The current study was aimed to investigate intestinal BA
      transport at the molecular level in a pig model. Twelve young pigs (11.05 +/-
      0.11 kg) were randomly divided into 2 groups and fed corn-soybean meal diets with
      either 5% pectin or cornstarch for 72 d. In pigs fed with pectin, total
      cholesterol and low-density lipoprotein cholesterol (LDL-C) were lowered but high
      density lipoprotein (HDL-C) was increased (P < 0.05). Serum triglycerides tended
      to be lower in the pectin-fed animals (P = 0.093), whereas no change was noted in
      serum total bile acid. Along the length of the intestine, the size and
      composition of BA pools vary. The ratio of primary, secondary, taurine
      conjugated, and glycine-conjugated BAs in the ileal pool was about 46:15:9:30,
      whereas it was 28:61:1:11 in the cecum and 22:65:3:9 in the colon (P < 0.05). In
      the feces, lithocholic acid and ursodeoxycholic acid (UDCA) made up of over 97%
      of the total BA pool. Overall, the ileum had the greatest expression of farnesoid
      X receptor (FXR) and apical sodium-coupled bile acid transporter (ASBT) than the
      duodenum, jejunum, cecum, and colon (P < 0.05), whereas organic solute
      transporters alpha/beta (OSTalpha/beta) gene expression was peaked in the ileum
      and jejunum (P < 0.05). Expression multidrug resistance protein 2 (MRP2)
      gradually decreased towards the end of the intestine (P < 0.05). Greater
      expression of G protein-coupled bile acid receptor and multidrug resistance
      protein 3 (MRP3) was found in the cecum and colon (P < 0.05). In pigs fed with 5%
      pectin, only cecal UDCA (P = 0.097) and hyocholic acid (P = 0.088) showed a
      decreasing tendency. But FXR, ASBT, and MRP2 were upregulated in the ileum and
      FXR, OSTalpha/beta, MRP2, and MRP3 in the cecum of PEC-fed pigs (P < 0.05). Liver
      enzymes involved in BA biosynthesis (CYP7A1, CYP27A1, bile acid-CoA synthase, and
      bile acid-CoA:amino acid N acyltransferase) were not affected by pectin
      consumption. In conclusion, the abundant distribution of BA transporters and the
      greater BA pool size suggests the ileum as the major site for intestinal BA
      reabsorption in pigs. In the ileum, pectin increased in-and-out BA transport on
      the apical membrane by increasing ASBT and MRP2, but it increased the overall BA
      transport in the cecum by increasing OSTalpha/beta and MRP3.

PMID- 30102378
TI  - Mean 6-Year Follow-up of Magnetically Controlled Growing Rod Patients With Early
      Onset Scoliosis: A Glimpse of What Happens to Graduates.
AB  - BACKGROUND: There is no agreement on frequency of distractions of magnetically
      controlled growing rods (MCGRs) but more frequent and smaller amounts of
      distractions mimic physiological spine growth. The mid- to long-term follow-up
      and management at skeletal maturity is unknown. OBJECTIVE: To analyze patients
      with mean 6 yr of follow-up and describe the fate of MCGR graduates. METHODS:
      Early onset scoliosis (EOS) patients treated with MCGRs with minimum 4 yr of
      follow-up and/or at graduation were studied. Parameters under study included Cobb
      angle, spine and instrumented lengths, and rod distraction gains. Relationship
      between timing of rod exchanges with changes in rate of lengthening was studied.
      RESULTS: Ten EOS patients with mean 6.1 yr of follow-up were studied. The
      greatest Cobb angle correction occurred at the initial implantation surgery and
      was stable thereafter. Consistent gains in T1-12, T1-S1, and instrumented segment
      were observed. Rate of lengthening reduced after the first year of use but
      improved back to initial rates after rod exchange. Seven of the ten patients
      experienced complications with reoperation rate of 40% for rod distraction
      failure and proximal foundation problems. Only mild further improvements in all
      radiological parameters were observed pre- and postfinal surgery. No clinically
      significant curve progression was observed for rod removal only. All postfinal
      surgery parameters remained similar at postoperative 2 yr. CONCLUSION: This study
      provides an outlook of the end of MCGR treatment. Although this is a fusionless
      procedure, instrumented segments do experience stiffness limiting further
      correction and length gain during final surgery whether fusion or rod removal is
      performed.

PMID- 30102381
TI  - Expression of interleukin-18 in muscle tissue of patients with polymyositis or
      dermatomyositis and effects of conventional immunosuppressive treatment.
AB  - Objectives: To investigate the expression of IL-18 in symptomatic and
      asymptomatic muscle tissues of patients with PM and DM and the effects of
      conventional immunosuppressive treatment on such expression. Methods: Two cohorts
      of patients were included in this study. The first cohort consisted of 10 new
      onset myositis patients. IL-18 expression was compared between symptomatic and
      asymptomatic muscle biopsies that were taken prior to treatment. The second
      cohort consisted of another 10 patients with repeated muscle biopsies before and
      after 8 months with conventional immunosuppressive treatment. Using
      immunohistochemistry, IL-18 expression in muscle tissues was compared before and
      after treatment. Biopsies from seven healthy individuals were included as
      controls. Results: IL-18 expression was predominantly localized to inflammatory
      cells and capillaries in patients and mostly to capillaries in healthy controls.
      Total IL-18 expression in muscle tissues from the new-onset patients, at both
      symptomatic and asymptomatic sites, was significantly higher compared with
      healthy controls (P = 0.007 and P = 0.002) with no statistical difference in
      appearances between symptomatic and asymptomatic sites. The number of IL-18
      positive capillaries was not different among symptomatic, asymptomatic and
      healthy muscles. Total IL-18 expression appeared lower in biopsies from patients
      receiving and improving with immunosuppressive treatment, particularly the number
      of IL-18 positive inflammatory cells but not the number of IL-18 positive
      capillaries, which was consistent with significantly decreased expression of
      CD68+ macrophages (P = 0.04). Conclusion: IL-18 is highly expressed in muscle
      tissue in the context of inflammatory myopathies and based on its plausible
      effector functions could provide a novel therapeutic target in future.

PMID- 30102379
TI  - Chromatin-dependent allosteric regulation of DNMT3A activity by MeCP2.
AB  - Despite their central importance in mammalian development, the mechanisms that
      regulate the DNA methylation machinery and thereby the generation of genomic
      methylation patterns are still poorly understood. Here, we identify the 5mC
      binding protein MeCP2 as a direct and strong interactor of DNA methyltransferase
      3 (DNMT3) proteins. We mapped the interaction interface to the transcriptional
      repression domain of MeCP2 and the ADD domain of DNMT3A and find that binding of
      MeCP2 strongly inhibits the activity of DNMT3A in vitro. This effect was
      reinforced by cellular studies where a global reduction of DNA methylation levels
      was observed after overexpression of MeCP2 in human cells. By engineering
      conformationally locked DNMT3A variants as novel tools to study the allosteric
      regulation of this enzyme, we show that MeCP2 stabilizes the closed,
      autoinhibitory conformation of DNMT3A. Interestingly, the interaction with MeCP2
      and its resulting inhibition were relieved by the binding of K4 unmodified
      histone H3 N-terminal tail to the DNMT3A-ADD domain. Taken together, our data
      indicate that the localization and activity of DNMT3A are under the combined
      control of MeCP2 and H3 tail modifications where, depending on the modification
      status of the H3 tail at the binding sites, MeCP2 can act as either a repressor
      or activator of DNA methylation.

PMID- 30102380
TI  - Loss of hierarchical imprinting regulation at the Prader-Willi/Angelman syndrome
      locus in human iPSCs.
AB  - The human chr15q11-q13 imprinted cluster is linked to several disorders,
      including Prader-Willi (PWS) and Angelman (AS) syndromes. Recently, disease
      modeling approaches based on induced pluripotent stem cells (iPSCs) have been
      used to study these syndromes. A concern regarding the use of these cells for
      imprinted disease modeling is the numerous imprinting defects found in many
      iPSCs. Here, by reprogramming skin fibroblasts from a control and AS individuals,
      we generated several iPSC lines and addressed the stability of imprinting status
      across the PWS/AS domain. We focused on three important regulatory DNA elements
      which are all differentially methylated regions (DMRs), methylated on the
      maternal allele: the PWS imprinting center (PWS-IC), which is a germline DMR and
      the somatic NDN and MKRN3 DMRs, hierarchically controlled by PWS-IC. Normal PWS
      IC methylation pattern was maintained in most iPSC lines; however, loss of
      maternal methylation in one out of five control iPSC lines resulted in a
      monoallelic to biallelic switch for many imprinted genes in this domain.
      Surprisingly, MKRN3 DMR was found aberrantly hypermethylated in all control and
      AS iPSCs, regardless of the methylation status of the PWS-IC master regulator.
      This suggests a loss of hierarchical control of imprinting at PWS/AS region. We
      confirmed these results in established iPSC lines derived using different
      reprogramming procedures. Overall, we show that hierarchy of imprinting control
      in donor cells might not apply to iPSCs, accounting for their spectrum of
      imprinting alterations. Such differences in imprinting regulation should be taken
      into consideration for the use of iPSCs in disease modeling.

PMID- 30102383
TI  - The effects of tobacco smoking, and prenatal tobacco smoke exposure, on risk of
      schizophrenia: a systematic review and meta-analysis.
AB  - Introduction: The association between cigarette smoking and schizophrenia is well
      established. However, up to 90% of people with schizophrenia begin smoking before
      the onset of their illness, thus smoking could be an independent risk factor for
      schizophrenia. Prenatal exposure to maternal cigarette smoke is also associated
      with psychiatric problems in adolescence. Therefore, our aim was to undertake a
      systematic review and meta-analysis to explore the effect of smoking, and
      prenatal smoke exposure, on risk of schizophrenia. Method: We systematically
      searched Medline, Embase, PsychInfo, Maternity and Infant Care, and Web of
      Science (from inception to February 2018) to identify comparative observational
      studies of the risk of schizophrenia in relation to smoking status. Measures of
      Relative Risk (RR) were pooled in a meta-analysis with 95% confidence intervals,
      using random effects model. Results: Twelve studies (9 cohort, 3 case-control)
      were included. Odds ratios (OR) and hazard ratios (HR) were pooled together to
      estimate pooled RRs and estimates combined in a meta-analysis on an assumption of
      constant risk over time. Smokers had a significantly increased risk of
      schizophrenia compared to non-smokers (RR 1.99, 95% CI 1.10-3.61, I2= 97%, 5
      studies). Exposure to prenatal smoke increased the risk of schizophrenia by 29%
      (95% CI 1.10-1.51, I2= 71%, 7 studies). Sensitivity analyses identified no
      significant differences between the results from studies reporting OR and HR.
      Conclusions: Our findings suggest smoking, and prenatal smoke exposure, may be an
      independent risk factor for schizophrenia. Care should be taken when inferring
      causation, given the observational nature of the studies. Implications: In this
      meta-analysis of 12 studies smokers had a significantly increased risk of
      schizophrenia compared to non-smokers. Exposure to prenatal tobacco smoke also
      increased the risk of schizophrenia by 29% compared to those with no exposure to
      prenatal tobacco smoke. Our findings suggest that smoking, and prenatal tobacco
      smoke exposure, may be independent risk factors for schizophrenia. These results
      may have important public health implications for decreasing the incidence of
      schizophrenia. The possibility of a causal link between smoking and schizophrenia
      warrants further investigation.

PMID- 30102382
TI  - Structural characterization of maternally expressed gene 3 RNA reveals conserved
      motifs and potential sites of interaction with polycomb repressive complex 2.
AB  - Long non-coding RNAs (lncRNAs) have emerged as key players in gene regulation.
      However, our incomplete understanding of the structure of lncRNAs has hindered
      molecular characterization of their function. Maternally expressed gene 3 (Meg3)
      lncRNA is a tumor suppressor that is downregulated in various types of cancer.
      Mechanistic studies have reported a role for Meg3 in epigenetic regulation by
      interacting with chromatin-modifying complexes such as the polycomb repressive
      complex 2 (PRC2), guiding them to genomic sites via DNA-RNA triplex formation.
      Resolving the structure of Meg3 RNA and characterizing its interactions with
      cellular binding partners will deepen our understanding of tumorigenesis and
      provide a framework for RNA-based anti-cancer therapies. Herein, we characterize
      the architectural landscape of Meg3 RNA and its interactions with PRC2 from a
      functional standpoint.

PMID- 30102384
TI  - Loss of CG methylation in Marchantia polymorpha causes disorganization of cell
      division and reveals unique DNA methylation regulatory mechanisms of non-CG
      methylation.
AB  - DNA methylation is an epigenetic mark that ensures silencing of transposable
      elements (TEs) and affects gene expression in many organisms. The function of
      different DNA methylation regulatory pathways has been largely characterized in
      the model plant Arabidopsis thaliana. However, far less is known about DNA
      methylation regulation and functions in basal land plants. Here we focus on the
      liverwort Marchantia polymorpha, an emerging model species that represents a
      basal lineage of land plants. We identified MpMET, the M. polymorpha orthologue
      of the METHYLTRANSFERASE 1 (MET1) gene required for maintenance of methylation at
      CG sites in angiosperms. We generated Mpmet mutants using the CRISPR/Cas9 system,
      which showed a significant loss of CG methylation and severe morphological
      changes and developmental defects. The mutants developed many adventitious shoot
      like structures, suggesting that MpMET is required for maintaining differentiated
      cellular identities in the gametophyte. Even though numerous TEs were up
      regulated, non-CG methylation was generally highly increased at TEs in the Mpmet
      mutants. Closer inspection of CHG methylation revealed features unique to M.
      polymorpha. Methylation of CCG sites in M. polymorpha does not depend on MET1,
      unlike in A. thaliana and Physcomitrella patens. Furthermore, unlike A. thaliana,
      M. polymorpha shows higher methylation level at CAG sites than at other CHG
      contexts and CAG/CTG sites are mostly methylated asymmetrically. Interestingly,
      CAG and CTG methylation reached comparable levels and symmetry upon loss of CG
      methylation. Our results highlight the diversity of non-CG methylation regulatory
      mechanisms in plants.

PMID- 30102386
TI  - Molecular organization of the type II-A CRISPR adaptation module and its
      interaction with Cas9 via Csn2.
AB  - Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR
      associated (Cas) proteins provide microbial adaptive immunity against invading
      foreign nucleic acids. In type II-A CRISPR-Cas systems, the Cas1-Cas2 integrase
      complex and the subtype-specific Csn2 comprise the CRISPR adaptation module,
      which cooperates with the Cas9 nuclease effector for spacer selection. Here, we
      report the molecular organization of the Streptococcus pyogenes type II-A CRISPR
      adaptation module and its interaction with Cas9 via Csn2. We determined the
      crystal structure of S. pyogenes type II-A Cas2. Chromatographic and calorimetric
      analyses revealed the stoichiometry and topology of the type II-A adaptation
      module composed of Cas1, Cas2 and Csn2. We also demonstrated that Cas9 interacts
      with Csn2 in a direct and stoichiometric manner. Our results reveal a network of
      molecular interactions among type II-A Cas proteins and highlight the role of
      Csn2 in coordinating Cas components involved in the adaptation and interference
      stages of CRISPR-mediated immunity.

PMID- 30102385
TI  - Chemical genetic inhibition of DEAD-box proteins using covalent complementarity.
AB  - DEAD-box proteins are an essential class of enzymes involved in all stages of RNA
      metabolism. The study of DEAD-box proteins is challenging in a native setting
      since they are structurally similar, often essential and display dosage
      sensitivity. Pharmacological inhibition would be an ideal tool to probe the
      function of these enzymes. In this work, we describe a chemical genetic strategy
      for the specific inactivation of individual DEAD-box proteins with small molecule
      inhibitors using covalent complementarity. We identify a residue of low
      conservation within the P-loop of the nucleotide-binding site of DEAD-box
      proteins and show that it can be mutated to cysteine without a substantial loss
      of enzyme function to generate electrophile-sensitive mutants. We then present a
      series of small molecules that rapidly and specifically bind and inhibit
      electrophile-sensitive DEAD-box proteins with high selectivity over the wild-type
      enzyme. Thus, this approach can be used to systematically generate small molecule
      sensitive alleles of DEAD-box proteins, allowing for pharmacological inhibition
      and functional characterization of members of this enzyme family.

PMID- 30102388
TI  - Type of underwear worn and markers of testicular function among men attending a
      fertility center.
AB  - STUDY QUESTION: Is self-reported type of underwear worn associated with markers
      of testicular function among men at a fertility center? SUMMARY ANSWER: Men who
      reported most frequently wearing boxers had higher sperm concentration and total
      count, and lower FSH levels, compared to men who did not. WHAT IS KNOWN ALREADY:
      Elevated scrotal temperatures are known to adversely affect testicular function.
      However, the epidemiologic literature on type of underwear, as a proxy of scrotal
      temperature, and male testicular function is inconsistent. STUDY DESIGN, SIZE,
      DURATION: This is a cross-sectional study including 656 male partners of couples
      seeking infertility treatment at a fertility center (2000-2017).
      PARTICIPANTS/MATERIALS, SETTING, METHODS: Self-reported information on type of
      underwear worn was collected from a take-home questionnaire. Semen samples were
      analyzed following World Health Organization guidelines. Enzyme immunoassays were
      used to assess reproductive hormone levels and neutral comet assays for sperm DNA
      damage. We fit linear regression models to evaluate the association between
      underwear type and testicular function, adjusting for covariates and accounting
      for multiple semen samples. MAIN RESULTS AND THE ROLE OF CHANCE: Men had a median
      (interquartile range) age of 35.5 (32.0, 39.3) years and BMI of 26.3 (24.4, 29.9)
      kg/m2. About half of the men (53%; n = 345) reported usually wearing boxers. Men
      who reported primarily wearing boxers had a 25% higher sperm concentration (95%
      CI = 7, 31%), 17% higher total count (95% CI = 0, 28%) and 14% lower serum FSH
      levels (95% CI = -27, -1%) than men who reported not primarily wearing boxers.
      Sperm concentration and total count were inversely related to serum FSH.
      Furthermore, the differences in sperm concentration and total count according to
      type of underwear were attenuated after adjustment for serum FSH. No associations
      with other measured reproductive outcomes were observed. LIMITATIONS, REASONS FOR
      CAUTION: Our results may not be generalizable to men from the general population.
      Underwear use was self-reported in a questionnaire and there may be
      misclassification of the exposure. The cross-sectional design limits causal
      inference, and residual confounding is still possible owing to lack of
      information on other modifiable life styles that can also modify scrotal heat
      (e.g. type of trousers worn, textile fabric of the underwear). Blood sampling was
      not limited to the morning and, as a result, we may have missed associations with
      testosterone or other hormones with significant circadian variation despite
      statistical adjustment for time of blood draw. WIDER IMPLICATIONS OF THE
      FINDINGS: Certain styles of male underwear may impair spermatogenesis and this
      may result in a compensatory increase in gonadotrophin secretion, as reflected by
      higher serum FSH levels among men who reported most frequently wearing tight
      underwear. Confirmation of these findings, and in particular the findings on FSH
      levels suggesting a compensatory mechanism, is warranted. STUDY FUNDING/COMPETING
      INTEREST(S): The project was financed by Grants (R01ES022955, R01ES009718,
      P30ES000002, and K99ES026648) from the National Institutes of Health. None of the
      authors has any conflicts of interest to declare.

PMID- 30102389
TI  - Subclinical reactivation of cytomegalovirus drives CD4+CD28null T-cell expansion
      and impaired immune response to pneumococcal vaccination in ANCA-associated
      vasculitis.
AB  - Background: Infection is the leading cause of death in ANCA-associated vasculitis
      (AAV). Expansion of CD4+CD28null T-cells is associated with increased risk of
      infection and mortality, but is only present in cytomegalovirus-seropositive
      individuals. We hypothesised that subclinical cytomegalovirus reactivation drives
      CD4+CD28null T-cell expansion; that this is associated with impaired immune
      response to heterologous antigens, and that anti-viral therapy may ameliorate
      this. Methods: In a proof-of-concept open-label clinical trial, 38
      cytomegalovirus-seropositive AAV patients were randomised to receive valaciclovir
      for 6-months or no intervention. Cytomegalovirus reactivation was measured
      monthly in plasma and urine. CD4+CD28null T-cells were enumerated at baseline and
      at 6 months. At 6 months, 36 patients were vaccinated with a 13-valent
      pneumococcal vaccine. Serotype-specific IgG was assayed before and 4 weeks post
      vaccination to calculate the antibody-response-ratio (ARR). Results: Valaciclovir
      treatment suppressed subclinical cytomegalovirus reactivation and reduced
      CD4+CD28null T-cell proportion. CD4+CD28null T-cell reduction correlated with
      improved vaccine response, whilst cytomegalovirus reactivation associated with
      reduced response to vaccination. Furthermore, expansion of CD4+CD28null T-cells
      was associated with a reduction in the functional capacity of the CD4
      compartment. Conclusion: Suppression of cytomegalovirus may improve the immune
      response to a T-cell dependent pneumococcal vaccination in patients with AAV,
      thus offering potential clinical benefit. Trial registration identifier:
      NCT01633476.

PMID- 30102390
TI  - Progression of subclinical atherosclerosis in systemic lupus erythematosus versus
      rheumatoid arthritis: the impact of low disease activity.
AB  - Objectives: The progression of subclinical atherosclerosis in SLE and RA has not
      been comparatively assessed. We sought to investigate the impact of low disease
      activity and other disease-related factors on atherosclerosis progression in SLE
      vs RA. Methods: We performed a 3-year follow-up carotid and femoral artery
      ultrasound in 101 patients with SLE, 85 with RA and 85 controls after a baseline
      examination in 115 SLE and 1:1 age- and gender-matched RA patients and controls.
      We used logistic regression to compare atherosclerosis progression (new plaque
      development) between SLE and RA vs controls, and assess determinants of
      progression in SLE patients with different lupus low disease activity state
      (LLDAS) durations, adjusting for disease-related factors, antihypertensives,
      antiplatelets, statins and the Systemic Coronary Risk Evaluation 10-year
      cardiovascular risk. Results: The odds ratio (OR) of plaque progression vs
      controls was significantly higher in SLE (OR = 2.81, P = 0.043), but not in RA
      (OR = 2.22, P = 0.109). Results were similar in patients with low disease
      activity (88% of SLE, 74% of RA). Multivariate determinants of progression in SLE
      included antiphospholipid antibodies (OR = 2.00, P = 0.043) and Systemic Coronary
      Risk Evaluation (OR = 2.87, P = 0.019) for all patients, and additionally
      cumulative corticosteroid dose during follow-up (OR = 1.38, P = 0.013) and
      disease duration (OR = 1.20, P = 0.022) for patients in LLDAS over entire follow
      up. Results were similar for patients with shorter LLDAS durations (>75% or >50%
      of follow-up). Conclusion: Plaque progression is accelerated in SLE regardless of
      disease activity, and is associated with antiphospholipid antibodies and the
      Systemic Coronary Risk Evaluation. In LLDAS, cumulative corticosteroid dose and
      disease duration are additional determinants of progression.

PMID- 30102387
TI  - Double methylation of tRNA-U54 to 2'-O-methylthymidine (Tm) synergistically
      decreases immune response by Toll-like receptor 7.
AB  - Sensing of nucleic acids for molecular discrimination between self and non-self
      is a challenging task for the innate immune system. RNA acts as a potent stimulus
      for pattern recognition receptors including in particular human Toll-like
      receptor 7 (TLR7). Certain RNA modifications limit potentially harmful self
      recognition of endogenous RNA. Previous studies had identified the 2'-O
      methylation of guanosine 18 (Gm18) within tRNAs as an antagonist of TLR7 leading
      to an impaired immune response. However, human tRNALys3 was non-stimulatory
      despite lacking Gm18. To identify the underlying molecular principle, interferon
      responses of human peripheral blood mononuclear cells to differentially modified
      tRNALys3 were determined. The investigation of synthetic modivariants allowed
      attributing a significant part of the immunosilencing effect to the 2'-O
      methylthymidine (m5Um) modification at position 54. The effect was contingent
      upon the synergistic presence of both methyl groups at positions C5 and 2'O, as
      shown by the fact that neither Um54 nor m5U54 produced any effect alone. Testing
      permutations of the nucleobase at ribose-methylated position 54 suggested that
      the extent of silencing and antagonism of the TLR7 response was governed by
      hydrogen patterns and lipophilic interactions of the nucleobase. The results
      identify a new immune-modulatory endogenous RNA modification that limits TLR7
      activation by RNA.

PMID- 30102393
TI  - Differences in the Associations between Memory Complaints and Depressive Symptoms
      among Black and White Older Adults.
AB  - Objective: To test whether race (specifically Black or White) moderates the
      relationship between memory complaints and depressive symptoms in cognitively
      normal older adults, and if these relationships vary by memory complaint
      characteristics. Methods: Data from Black (n = 551) and White (n = 1158)
      cognitively intact participants (Mage = 77.1, SD = 7.5; 76.6% female) in the
      Minority Aging Research Study and the Rush Memory and Aging Project were used.
      Participants completed annual clinical evaluations, including the Center for
      Epidemiologic Studies Depression scale and two memory complaint questions, over
      periods of up to 18 years. Ordinal mixed effects models were used to examine
      within-person relationships between memory complaints and depressive symptoms
      over time, as well as whether race moderated these associations. Results: Reports
      of greater memory change over time were associated with more depressive symptoms
      for both Black and White older adults. However, reports of greater frequency of
      memory problems were related to depressive symptoms for Black older adults only.
      Conclusion: Findings suggest differential associations between memory complaints
      and depressive symptoms in cognitively normal Black and White older adults and
      call for future research to examine the influence of race and related factors on
      memory complaints and depressive symptoms.

PMID- 30102392
TI  - Members of the DUF231 Family are O-Acetyltransferases Catalyzing 2-O- and 3-O
      Acetylation of Mannan.
AB  - Mannans are hemicellulosic polysaccharides commonly found in the primary and
      secondary cell walls of land plants, and their mannosyl residues are often
      acetylated at O-2 and O-3. Currently, little is known about the genes responsible
      for the acetylation of mannans. In this report, we investigated the roles of a
      subgroup of DUF231 proteins including 11 from Arabidopsis thaliana and one from
      Amorphophallus konjac in mannan acetylation. Acetyltransferase activity assays of
      their recombinant proteins revealed that four Arabidopsis DUF231 proteins
      possessed an enzymatic activity capable of transferring acetyl groups from acetyl
      CoA onto the mannohexaose acceptor, and thus were named mannan O
      acetyltransferases (MOAT1, MOAT2, MOAT3 and MOAT4). Their close homolog from A.
      konjac (named AkMOAT1) also exhibited mannan O-acetyltransferase activity.
      Structural analysis of the MOAT-catalyzed reaction products demonstrated that
      these MOATs catalyzed 2-O- and 3-O-monoacetylation of mannosyl residues, an
      acetyl substitution pattern similar to that of Arabidopsis glucomannan. Site
      directed mutagenesis showed that mutations of the conserved residues in the GDS
      and DXXH motifs of MOAT3 abolished its acetyltransferase activity, indicating the
      essential roles of these motifs in its activity. In addition, simultaneous RNA
      interference (RNAi) inhibition of the expression of the four Arabidopsis MOAT
      genes led to a drastic reduction in the degree of acetyl substitutions in
      glucomannan, further corroborating their role in glucomannan acetylation.
      Together, these results present the first lines of biochemical and genetic
      evidence demonstrating that these four Arabidopsis DUF231 members and their close
      A. konjac homolog are mannan O-acetyltransferases.

PMID- 30102391
TI  - Insights into the development of chemical probes for RNA.
AB  - Over the past decade, the RNA revolution has revealed thousands of non-coding
      RNAs that are essential for cellular regulation and are misregulated in disease.
      While the development of methods and tools to study these RNAs has been
      challenging, the power and promise of small molecule chemical probes is
      increasingly recognized. To harness existing knowledge, we compiled a list of 116
      ligands with reported activity against RNA targets in biological systems (R
      BIND). In this survey, we examine the RNA targets, design and discovery
      strategies, and chemical probe characterization techniques of these ligands. We
      discuss the applicability of current tools to identify and evaluate RNA-targeted
      chemical probes, suggest criteria to assess the quality of RNA chemical probes
      and targets, and propose areas where new tools are particularly needed. We
      anticipate that this knowledge will expedite the discovery of RNA-targeted
      ligands and the next phase of the RNA revolution.

PMID- 30102394
TI  - The trimeric Hef-associated nuclease HAN is a 3'->5' exonuclease and is probably
      involved in DNA repair.
AB  - Nucleases play important roles in nucleic acid metabolism. Some archaea encode a
      conserved protein known as Hef-associated nuclease (HAN). In addition to its C
      terminal DHH nuclease domain, HAN also has three N-terminal domains, including a
      DnaJ-Zinc-finger, ribosomal protein S1-like, and oligonucleotide/oligosaccharide
      binding fold. To further understand HAN's function, we biochemically
      characterized the enzymatic properties of HAN from Pyrococcus furiosus (PfuHAN),
      solved the crystal structure of its DHH nuclease domain, and examined its role in
      DNA repair. Our results show that PfuHAN is a Mn2+-dependent 3'-exonuclease
      specific to ssDNA and ssRNA with no activity on blunt and 3'-recessive double
      stranded DNA. Domain truncation confirmed that the intrinsic nuclease activity is
      dependent on the C-terminal DHH nuclease domain. The crystal structure of the DHH
      nuclease domain adopts a trimeric topology, with each subunit adopting a
      classical DHH phosphoesterase fold. Yeast two hybrid assay confirmed that the DHH
      domain interacts with the IDR peptide of Hef nuclease. Knockout of the han gene
      or its C-terminal DHH nuclease domain in Haloferax volcanii resulted in increased
      sensitivity to the DNA damage reagent MMS. Our results imply that HAN nuclease
      might be involved in repairing stalled replication forks in archaea.

PMID- 30102396
TI  - SP140 regulates the expression of immune-related genes associated with multiple
      sclerosis and other autoimmune diseases by NF-kappaB inhibition.
AB  - SP140 locus has been associated with multiple sclerosis (MS) as well as other
      autoimmune diseases by genome-wide association studies (GWAS). The causal variant
      of these associations (rs28445040-T) alters the splicing of the SP140 gene
      transcripts reducing the protein expression. We aimed to understand why the
      reduction of SP140 expression produced by the risk variant can increase the
      susceptibility to MS. To this end, we determined by RNA sequencing (RNA-seq)
      analysis the differentially expressed genes after SP140 silencing in
      lymphoblastoid cell lines (LCLs). We analyzed these genes by gene ontology (GO),
      comparative transcriptome profiles, enrichment of transcription factors (TFs) in
      the promoters of these genes and colocalization with GWAS risk variants. We also
      monitored the activity of the nuclear factor kappa-light-chain-enhancer of
      activated B cells (NF-kappaB) in SP140-silenced cells by luciferase reporter
      system. We identified 100 genes that were up-regulated and 22 genes down
      regulated in SP140-silenced LCLs. GO analysis revealed that genes affected by
      SP140 were involved in regulation of cytokine production, inflammatory response
      and cell-cell adhesion. We observed enrichment of NF-kappaB TF in the promoter of
      up-regulated genes and NF-kappaB-increased activity in SP140-silenced cell lines.
      We showed enrichment of genes regulated by SP140 in GWAS-detected risk loci for
      MS (14.63 folds), Crohn's disease (4.82 folds) and inflammatory bowel disease
      (4.47 folds), not observed in other unrelated immune diseases. Our findings
      showed that SP140 is an important repressor of genes implicated in inflammation,
      suggesting that decreased expression of SP140, promoted by the rs28445040-T risk
      variant, may lead to up-regulation of these genes by means of NF-kappaB
      inhibition in B cells.

PMID- 30102397
TI  - Effectiveness of India's National Programme to save the girl child: experience of
      Beti Bachao Beti Padao (B3P) programme from Haryana State.
AB  - The Government of India launched a nationwide programme to save and educate the
      girl child, Beti Bachao Beti Padhao (B3P), by stringent prohibition of sex
      selective abortion, enforcement of Preconception and Prenatal Diagnostic
      Technique (PC-PNDT) and Medical Termination of Pregnancy (MTP) Acts, and social
      mobilization. We undertook this study to assess the effectiveness of intervention
      in Haryana state to improve sex ratio at birth (SRB). The monthly data on SRB
      (represented as girls per 1000 boys) were collected from civil registration
      system for the entire state of Haryana to evaluate the impact of B3P programme.
      The segmented time-series regression analysis was used to estimate the change in
      SRB after B3P programme. In this process, the seasonal auto regressive integrated
      moving average model was used to control the seasonality, autocorrelation and
      secular trend imbibed in the data before calculating the estimate of change in
      slope using regression equation. Overall, the sex ratio at birth in Haryana
      increased from 827 girls per 1000 boys in January 2005 to 900 girls per 1000 boys
      in September 2016. The estimates from segmented time-series regression analysis
      show that there was an insignificant change in SRB of -0.012 units before the
      intervention. Post slope was estimated to be 1.684, which suggested an increase
      in SRB of 1.696 [(confidence interval: 0.23, 3.15), P = 0.025] in terms of the
      difference between pre- and post-slope. This indicates a statistically
      significant increase of SRB by 1.696 per month attributable to B3P programme. B3P
      programme has resulted in an improvement of SRB in Haryana.

PMID- 30102395
TI  - A Freeloader? The Highly Eroded Yet Large Genome of the Serratia symbiotica
      Symbiont of Cinara strobi.
AB  - Genome reduction is pervasive among maternally inherited bacterial endosymbionts.
      This genome reduction can eventually lead to serious deterioration of essential
      metabolic pathways, thus rendering an obligate endosymbiont unable to provide
      essential nutrients to its host. This loss of essential pathways can lead to
      either symbiont complementation (sharing of the nutrient production with a novel
      co-obligate symbiont) or symbiont replacement (complete takeover of nutrient
      production by the novel symbiont). However, the process by which these two
      evolutionary events happen remains somewhat enigmatic by the lack of examples of
      intermediate stages of this process. Cinara aphids (Hemiptera: Aphididae)
      typically harbor two obligate bacterial symbionts: Buchnera and Serratia
      symbiotica. However, the latter has been replaced by different bacterial taxa in
      specific lineages, and thus species within this aphid lineage could provide
      important clues into the process of symbiont replacement. In the present study,
      using 16S rRNA high-throughput amplicon sequencing, we determined that the aphid
      Cinara strobi harbors not two, but three fixed bacterial symbionts: Buchnera
      aphidicola, a Sodalis sp., and S. symbiotica. Through genome assembly and genome
      based metabolic inference, we have found that only the first two symbionts
      (Buchnera and Sodalis) actually contribute to the hosts' supply of essential
      nutrients while S. symbiotica has become unable to contribute towards this task.
      We found that S. symbiotica has a rather large and highly eroded genome which
      codes only for a few proteins and displays extensive pseudogenization. Thus, we
      propose an ongoing symbiont replacement within C. strobi, in which a once
      "competent" S. symbiotica does no longer contribute towards the beneficial
      association. These results suggest that in dual symbiotic systems, when a
      substitute cosymbiont is available, genome deterioration can precede genome
      reduction and a symbiont can be maintained despite the apparent lack of benefit
      to its host.

PMID- 30102398
TI  - FACER: comprehensive molecular and functional characterization of epigenetic
      chromatin regulators.
AB  - Epigenetic alterations, a well-recognized cancer hallmark, are driven by
      chromatin regulators (CRs). However, little is known about the extent of CR
      deregulation in cancer, and less is known about their common and specialized
      roles across various cancers. Here, we performed genome-wide analyses and
      constructed molecular signatures and network profiles of functional CRs in over
      10 000 tumors across 33 cancer types. By integration of DNA mutation, genome-wide
      methylation, transcriptional/post-transcriptional regulation, and protein
      interaction networks with clinical outcomes, we identified CRs associated with
      cancer subtypes and clinical prognosis as potential oncogenic drivers.
      Comparative network analysis revealed principles of CR regulatory specificity and
      functionality. In addition, we identified common and specific CRs by assessing
      their prevalence across cancer types. Common CRs tend to be histone modifiers and
      chromatin remodelers with fundamental roles, whereas specialized CRs are involved
      in context-dependent functions. Finally, we have made a user-friendly web
      interface-FACER (Functional Atlas of Chromatin Epigenetic Regulators) available
      for exploring clinically relevant CRs for the development of CR biomarkers and
      therapeutic targets. Our integrative analysis reveals specific determinants of
      CRs across cancer types and presents a resource for investigating disease
      associated CRs.

PMID- 30102400
TI  - Chronic Q fever: patient and treatment-related factors influencing long-term
      quality of life.
AB  - Background: Chronic Q fever is accompanied by high mortality and morbidity, and
      requires prolonged antibiotic treatment. Little is known on long-term quality of
      life (LQOL) in chronic Q fever patients treated with antibiotics. Aim: To
      identify patient and treatment-related factors associated with impaired LQOL in
      chronic Q fever patients treated with antibiotics, and to assess patients'
      perception on treatment. Design: Cross-sectional study. Methods: LQOL was
      assessed with a validated questionnaire from the Nijmegen Clinical Screening
      Instrument. Patients' perception on treatment was measured with three newly
      developed questions. Results: We included 64 patients: LQOL was impaired in 55%
      (n = 35) after a median follow-up of 5 years. Median treatment duration was 27
      months. In multivariable analysis, treatment duration was significantly
      associated with impaired LQOL (OR 1.07; 95%CI 1.02-1.12, P < 0.01 per month
      increase). Age, gender, number of antibiotic regimens, surgical intervention,
      complications, diagnostic classification, focus of infection or registration of
      side effects during treatment were not associated with impaired LQOL. After start
      of treatment, 17 patients (27%) perceived improvement of their condition.
      Disadvantages of treatment were experienced on a daily basis by 24 patients (69%)
      with impaired LQOL and 13 patients (46%) without impaired LQOL (P = 0.04).
      Conclusions: LQOL in chronic Q fever patients treated with antibiotics is
      impaired in more than half of patients 5 years after diagnosis. Antibiotic
      treatment duration was the only variable associated with impaired LQOL. The
      majority of patients experienced disadvantages on a daily basis, highlighting the
      high burden of disease and treatment.

PMID- 30102399
TI  - Patient perceptions of curability and physician-reported disclosures of
      incurability in Japanese patients with unresectable/recurrent cancer: a cross
      sectional survey.
AB  - Background: Although reports have described the perceptions of curability among
      patients with unresectable/recurrent cancer and the quality of death and dying,
      the association between patients' perceptions and physicians' disclosures of
      incurability remained unexplored. This survey aimed to evaluate the association
      between patients' perceptions of curability and physicians' disclosures of
      incurability. Methods: In this cross-sectional, multicenter, observational study
      in Japan, we asked outpatients with unresectable/recurrent solid cancers about
      their perceptions of incurability. The patient inclusion criteria were
      unresectable/recurrent solid cancer, failure of first-line chemotherapy and an
      age >= 20 years. Additionally, we surveyed their primary responsible physicians
      regarding disclosures to patients regarding incurability. Results: Although we
      estimated the necessary sample size as 250, we discontinued recruitment because
      the responsible researcher transferred to another hospital. Among the 135
      included and surveyed patients, 39% responded that their cancer was incurable,
      33% responded that their cancer was curable and 23% responded 'I don't know' or
      'I don't wish to answer'. No significant association was observed between
      patients' perceptions of curability and physician-reported disclosures of
      incurability. Conclusion: In this Japanese population, 39% of patients with
      unresectable/recurrent solid cancers perceived that their cancers were incurable.
      However, such perceptions did not appear to be significantly affected by
      physician-reported disclosures. We recommend additional research to determine the
      best disclosure method to ensure that patients truly understand their disease
      status.

PMID- 30102402
TI  - Impulse model-based differential expression analysis of time course sequencing
      data.
AB  - Temporal changes to the concentration of molecular species such as mRNA, which
      take place in response to various environmental cues, can often be modeled as
      simple continuous functions such as a single pulse (impulse) model. The
      simplicity of such functional representations can provide an improved performance
      on fundamental tasks such as noise reduction, imputation and differential
      expression analysis. However, temporal gene expression profiles are often studied
      with models that treat time as a categorical variable, neglecting the dependence
      between time points. Here, we present ImpulseDE2, a framework for differential
      expression analysis that combines the power of the impulse model as a continuous
      representation of temporal responses along with a noise model tailored
      specifically to sequencing data. We compare the simple categorical models to
      ImpulseDE2 and to other continuous models based on natural cubic splines and
      demonstrate the utility of the continuous approach for studying differential
      expression in time course sequencing experiments. A unique feature of ImpulseDE2
      is the ability to distinguish permanently from transiently up- or down-regulated
      genes. Using an in vitro differentiation dataset, we demonstrate that this gene
      classification scheme can be used to highlight distinct transcriptional programs
      that are associated with different phases of the differentiation process.

PMID- 30102401
TI  - In vivo genome-wide binding interactions of mouse and human constitutive
      androstane receptors reveal novel gene targets.
AB  - The constitutive androstane receptor (CAR; NR1I3) is a nuclear receptor
      orchestrating complex roles in cell and systems biology. Species differences in
      CAR's effector pathways remain poorly understood, including its role in
      regulating liver tumor promotion. We developed transgenic mouse models to assess
      genome-wide binding of mouse and human CAR, following receptor activation in
      liver with direct ligands and with phenobarbital, an indirect CAR activator.
      Genomic interaction profiles were integrated with transcriptional and biological
      pathway analyses. Newly identified CAR target genes included Gdf15 and Foxo3,
      important regulators of the carcinogenic process. Approximately 1000 genes
      exhibited differential binding interactions between mouse and human CAR,
      including the proto-oncogenes, Myc and Ikbke, which demonstrated preferential
      binding by mouse CAR as well as mouse CAR-selective transcriptional enhancement.
      The ChIP-exo analyses also identified distinct binding motifs for the respective
      mouse and human receptors. Together, the results provide new insights into the
      important roles that CAR contributes as a key modulator of numerous signaling
      pathways in mammalian organisms, presenting a genomic context that specifies
      species variation in biological processes under CAR's control, including liver
      cell proliferation and tumor promotion.

PMID- 30102403
TI  - QstR-dependent regulation of natural competence and type VI secretion in Vibrio
      cholerae.
AB  - During growth on chitinous surfaces in its natural aquatic environment Vibrio
      cholerae develops natural competence for transformation and kills neighboring non
      immune bacteria using a type VI secretion system (T6SS). Activation of these two
      phenotypes requires the chitin-induced regulator TfoX, but also integrates
      signals from quorum sensing via the intermediate regulator QstR, which belongs to
      the LuxR-type family of regulators. Here, we define the QstR regulon using RNA
      sequencing. Moreover, by mapping QstR binding sites using chromatin
      immunoprecipitation coupled with deep sequencing we demonstrate that QstR is a
      transcription factor that binds upstream of the up- and down-regulated genes.
      Like other LuxR-type family transcriptional regulators we show that QstR function
      is dependent on dimerization. However, in contrast to the well-studied LuxR-type
      biofilm regulator VpsT of V. cholerae, which requires the second messenger c-di
      GMP, we show that QstR dimerization and function is c-di-GMP independent.
      Surprisingly, although ComEA, which is a periplasmic DNA-binding protein
      essential for transformation, is produced in a QstR-dependent manner, QstR
      binding was not detected upstream of comEA suggesting the existence of a further
      regulatory pathway. Overall, these results provide detailed insights into the
      function of a key regulator of natural competence and type VI secretion in V.
      cholerae.

PMID- 30102404
TI  - A piRNA utilizes HILI and HIWI2 mediated pathway to down-regulate ferritin heavy
      chain 1 mRNA in human somatic cells.
AB  - The piwi interacting RNAs (piRNAs) are small non-coding RNAs that specifically
      bind to the PIWI proteins, a functional requirement. The piRNAs regulate germline
      development, transposons control, and gene expression. However, piRNA-mediated
      post-transcriptional gene regulation in human somatic cells is not well
      understood. We discovered a human piRNA (piR-FTH1) which has a complementary
      sequence in the ferritin heavy chain 1 (Fth1) mRNA. We demonstrated that
      expression of piR-FTH1 and Fth1 are inversely correlated in the tested tumor cell
      lines. We found that piR-FTH1 negatively regulates the Fth1 expression at post
      transcriptional level in triple negative breast cancer (TNBC) cells.
      Additionally, we confirmed that transfected piR-FTH1 knocks down the Fth1 mRNA
      via the HIWI2 and HILI mediated mechanism. piR-FTH1 mediated Fth1 repression also
      increased doxorubicin sensitivity by a remarkable 20-fold in TNBC cells. Since
      the current piRNA-mediated knockdowns of target mRNA are mostly reported in germ
      line cells, piRNA-mediated post-transcriptional gene regulation in somatic cells
      is rather unique in its application and mechanistically uses an alternative
      pathway to siRNA and miRNA. This work begins to lay the groundwork with a broader
      impact on treatment of various diseases that are linked to elevated levels of
      specific mRNAs which have a piRNA target.

PMID- 30102405
TI  - p15PAF binding to PCNA modulates the DNA sliding surface.
AB  - p15PAF is an oncogenic intrinsically disordered protein that regulates DNA
      replication and lesion bypass by interacting with the human sliding clamp PCNA.
      In the absence of DNA, p15PAF traverses the PCNA ring via an extended PIP-box
      that contacts the sliding surface. Here, we probed the atomic-scale structure of
      p15PAF-PCNA-DNA ternary complexes. Crystallography and MD simulations show that,
      when p15PAF occupies two subunits of the PCNA homotrimer, DNA within the ring
      channel binds the unoccupied subunit. The structure of PCNA-bound p15PAF in the
      absence and presence of DNA is invariant, and solution NMR confirms that DNA does
      not displace p15PAF from the ring wall. Thus, p15PAF reduces the available
      sliding surfaces of PCNA, and may function as a belt that fastens the DNA to the
      clamp during synthesis by the replicative polymerase (pol delta). This
      constraint, however, may need to be released for efficient DNA lesion bypass by
      the translesion synthesis polymerase (pol eta). Accordingly, our biochemical data
      show that p15PAF impairs primer synthesis by pol eta-PCNA holoenzyme against both
      damaged and normal DNA templates. In light of our findings, we discuss the
      possible mechanistic roles of p15PAF in DNA replication and suppression of DNA
      lesion bypass.

PMID- 30102407
TI  - Expression of Genes Encoding for Xenobiotic Metabolism After Exposure to
      Dialkylnitrosamines in the Chicken Egg Genotoxicity Alternative Model.
AB  - The Chicken Egg Genotoxicity Assay (CEGA) demonstrated responsiveness to various
      DNA-reactive chemicals requiring metabolic activation, which implies broad
      bioactivation capability. To assess potential metabolic competence, expression
      profiles of metabolic genes in the embryo-chicken fetal liver were determined
      using microarray technology. Fertilized chicken eggs were injected under the CEGA
      protocol with vehicle (deionized water [DW]), the activation-dependent
      carcinogens, diethylnitrosamine (DEN), and N-nitrosodiethanolamine (NDELA) at
      doses producing no effect on survival. Previously in CEGA, DEN produced DNA
      damage, whereas NDELA did not. Expressions of 463 genes known to encode for phase
      I and II of endo- and xenobiotic metabolism were detected on the array. DW did
      not affect the expression of the selected genes, deregulating less than 1% of
      them. In contrast, DEN at 2 mg/egg and NDELA at 4 mg/egg produced significant
      transcriptomic alterations, up-regulating up to 41% and down-regulating over 31%
      of studied genes. Both nitrosamines modulated the majority of the genes in a
      similar manner, sharing 64 up-regulated and 93 down-regulated genes with respect
      to control group, indicating similarity in the regulation of their metabolism by
      avian liver. Differences in gene expression between DEN and NDELA were documented
      for several phase I CYP 450 genes that are responsible for nitrosamine
      biotransformation, as well as for phase II genes that regulate detoxication
      reactions. These findings could underlie the difference in genotoxicity of DEN
      and NDELA in CEGA. In conclusion, the analysis of gene expression profiles in
      embryo-chicken fetal liver dosed with dialkylnitrosamines demonstrated that avian
      species possess a complex array of inducible genes coding for biotransformation.

PMID- 30102408
TI  - DCARS: Differential correlation across ranked samples.
AB  - Motivation: Genes act as a system and not in isolation. Thus, it is important to
      consider coordinated changes of gene expression rather than single genes when
      investigating biological phenomena such as the aetiology of cancer. We have
      developed an approach for quantifying how changes in the association between
      pairs of genes may inform the outcome of interest called Differential Correlation
      across Ranked Samples (DCARS). Modelling gene correlation across a continuous
      sample ranking does not require the dichotomisation of samples into two distinct
      classes and can identify differences in gene correlation across early, mid or
      late stages of the outcome of interest. Results: When we evaluated DCARS against
      the typical Fisher Z-transformation test for differential correlation, as well as
      a typical approach testing for interaction within a linear model, on real TCGA
      data, DCARS significantly ranked gene pairs containing known cancer genes more
      highly across several cancers. Similar results are found with our simulation
      study. DCARS was applied to 13 cancers datasets in TCGA, revealing several
      distinct relationships for which survival ranking was found to be associated with
      a change in correlation between genes. Furthermore, we demonstrated that DCARS
      can be used in conjunction with network analysis techniques to extract biological
      meaning from multi-layered and complex data. Availability: DCARS R package and
      sample data are available at https://github.com/shazanfar/DCARS. Supplementary
      information: Supplementary data are available at Bioinformatics online.

PMID- 30102409
TI  - Are Urban Vertebrates City Specialists, Artificial Habitat Exploiters, or
      Environmental Generalists?
AB  - Although urbanization is a major threat to biodiversity, some species are able to
      thrive in cities. This might be because they have specific adaptations to urban
      conditions, because they are able to cope with artificial habitats in general or
      because they are generalists that can live in a wide range of conditions. We use
      the latest version of the IUCN database to distinguish these possibilities in
      25,985 species of the four classes of terrestrial vertebrates with the help of
      phylogenetically controlled methods. We first compare species occurrence in
      cities with that of the five other artificial habitats recognized by the IUCN and
      use principal components analyses to ask which of these most resembles cities. We
      then test whether urban species have a wider habitat breadth than species
      occurring in other, non-urban, artificial habitats, as well as species that occur
      only in natural habitats. Our results suggest that the proportion of terrestrial
      vertebrates that occur in urban environments is small and that, among the species
      that do occur in cities, the great majority also occur in other artificial
      habitats. Our data also show that the presence of terrestrial vertebrates in
      urban habitats is skewed in favor of habitat generalists. In birds and mammals,
      species occurrence in urban areas is most similar to that of rural gardens, while
      in reptiles and amphibians, urban areas most resemble pasture and arable land.
      Our study suggests that cities are likely not unique, as is often thought, and
      may resemble other types of artificial environments, which urban exploiters can
      adapt to because of their wide habitat breadth.

PMID- 30102406
TI  - RbpA relaxes promoter selectivity of M. tuberculosis RNA polymerase.
AB  - The transcriptional activator RbpA associates with Mycobacterium tuberculosis RNA
      polymerase (MtbRNAP) during transcription initiation, and stimulates formation of
      the MtbRNAP-promoter open complex (RPo). Here, we explored the influence of
      promoter motifs on RbpA-mediated activation of MtbRNAP containing the stress
      response sigmaB subunit. We show that both the 'extended -10' promoter motif (T
      17G-16T-15G-14) and RbpA stabilized RPo and allowed promoter opening at
      suboptimal temperatures. Furthermore, in the presence of the T-17G-16T-15G-14
      motif, RbpA was dispensable for RNA synthesis initiation, while exerting a
      stabilization effect on RPo. On the other hand, RbpA compensated for the lack of
      sequence-specific interactions of domains 3 and 4 of sigmaB with the extended -10
      and the -35 motifs, respectively. Mutations of the positively charged residues
      K73, K74 and R79 in RbpA basic linker (BL) had little effect on RPo formation,
      but affected MtbRNAP capacity for de novo transcription initiation. We propose
      that RbpA stimulates transcription by strengthening the non-specific interaction
      of the sigma subunit with promoter DNA upstream of the -10 element, and by
      indirectly optimizing MtbRNAP interaction with initiation substrates.
      Consequently, RbpA renders MtbRNAP promiscuous in promoter selection, thus
      compensating for the weak conservation of the -35 motif in mycobacteria.

PMID- 30102410
TI  - Modification of the aminopyridine unit of 2'-deoxyaminopyridinyl-pseudocytidine
      allowing triplex formation at CG interruptions in homopurine sequences.
AB  - The antigene strategy based on site-specific recognition of duplex DNA by triplex
      DNA formation has been exploited in a wide range of biological activities.
      However, specific triplex formation is mostly restricted to homo-purine strands
      within the target duplex DNA, due to the destabilizing effect of CG and TA
      inversion sites where there is an absence of natural nucleotides that can
      recognize the CG and TA base pairs. Hence, the design of artificial nucleosides,
      which can selectively recognize these inversion sites with high affinity, should
      be of great significance. Recently, we determined that 2-amino-3-methylpyridinyl
      pseudo-dC (3MeAP-PsidC) possessed significant affinity and selectivity toward a
      CG inversion site and showed effective inhibition of gene expression. We now
      describe the design and synthesis of new modified aminopyridine derivatives by
      focusing on small chemical modification of the aminopyridine unit to tune and
      enhance the selectivity and affinity toward CG inversion sites. Remarkably, we
      have newly found that 2-amino-4-methoxypyridinyl pseudo-dC (4OMeAP-PsidC) could
      selectively recognize the CG base pair in all four adjacent base pairs and form a
      stable triplex structure against the promoter sequence of the human gene
      including multiple CG inversion sites.

PMID- 30102411
TI  - Establishment of reference intervals for serum symmetric dimethylarginine in
      adult nonracing Greyhounds.
AB  - BACKGROUND: The reference intervals (RIs) for the renal biomarkers urea and
      creatinine, in Greyhounds, are higher than those for non-sighthound breeds. A
      recent study has demonstrated a higher concentration of another biomarker of
      renal function, symmetric dimethylarginine (SDMA), in Greyhounds compared with
      other dog breeds, and thus a breed-specific RI for serum SDMA may be appropriate
      for Greyhounds. Greyhounds appear to be predisposed to renal disease, and the
      establishment of an appropriate RI for SDMA may improve the ability to identify
      early renal dysfunction in this breed. OBJECTIVES: The aim of this study was to
      establish an RI for serum SDMA in nonracing Greyhounds and to determine whether
      the RI for Greyhounds is different from that of non-sighthound breeds. METHODS:
      Blood samples were collected from 101 clinically healthy, nonracing Greyhounds
      for serum SDMA measurements. Results from Greyhounds were compared with serum
      SDMA concentrations measured in a group of non-sighthound dogs (n = 24) of
      similar weight, age, and sex, and with a previously established canine serum SDMA
      RI. RESULTS: The serum SDMA RI for Greyhounds was 6.3-19.9 MUg/dL (0.31-0.99
      MUmol/L). Greyhounds had a significantly higher mean value (13.1 MUg/dL) than
      that of the non-sighthound dogs (10.2 MUg/dL) (P < .001), and the RI of
      Greyhounds was different from previously established canine RIs for SDMA.
      CONCLUSION: This study supports the use of a Greyhound-specific RI for SDMA.
      Using previously established canine RIs for this breed could result in the
      overdiagnosis of renal disease.

PMID- 30102412
TI  - Bile Microinfarcts in Cholestasis Are Initiated by Rupture of the Apical
      Hepatocyte Membrane and Cause Shunting of Bile to Sinusoidal Blood.
AB  - Bile duct ligation (BDL) is an experimental procedure that mimics obstructive
      cholestatic disease. One of the early consequences of BDL in rodents is the
      appearance of so-called bile infarcts that correspond to Charcot-Gombault
      necrosis in human cholestasis. The mechanisms causing bile infarcts and their
      pathophysiological relevance are unclear. Therefore, intravital two photon-based
      imaging of BDL mice was performed with fluorescent bile salts (BS) and non-BS
      organic anion analogues. Key findings were followed up by matrix-assisted laser
      desorption ionization imaging, clinical chemistry, immunostaining, and gene
      expression analyses. In the acute phase, 1-3 days after BDL, BS concentrations in
      bile increased and single-cell bile microinfarcts occurred in dispersed
      hepatocytes throughout the liver caused by the rupture of the apical hepatocyte
      membrane. This rupture occurred after loss of mitochondrial membrane potential,
      followed by entry of bile, cell death, and a "domino effect" of further death
      events of neighboring hepatocytes. Bile infarcts provided a trans-epithelial
      shunt between bile canaliculi and sinusoids by which bile constituents leaked
      into blood. In the chronic phase, >=21 days after BDL, uptake of BS tracers at
      the sinusoidal hepatocyte membrane was reduced. This contributes to elevated
      concentrations of BS in blood and decreased concentrations in the biliary tract.
      Conclusion: Bile microinfarcts occur in the acute phase after BDL in a limited
      number of dispersed hepatocytes followed by larger infarcts involving neighboring
      hepatocytes, and they allow leakage of bile from the BS-overloaded biliary tract
      into blood, thereby protecting the liver from BS toxicity; in the chronic phase
      after BDL, reduced sinusoidal BS uptake is a dominant protective factor, and the
      kidney contributes to the elimination of BS until cholemic nephropathy sets in.

PMID- 30102413
TI  - Population Pharmacokinetic and Exposure-Response Analysis of Selumetinib and Its
      N-desmethyl Metabolite in Patients With Non-Small Cell Lung Cancer.
AB  - Selumetinib (AZD6244, ARRAY-142886) is a mitogen-activated protein kinase kinase
      inhibitor that has been tested for treatment of non-small cell lung cancer
      (NSCLC). Selumetinib (75 mg twice daily) plus docetaxel in patients with advanced
      NSCLC has been assessed in phase 2 (SELECT-2) and phase 3 (SELECT-1) clinical
      trials. The objective of the current analysis was to investigate the exposure
      response relationship of selumetinib in these 2 clinical trials, based on the
      development of a population pharmacokinetic (PopPK) model for selumetinib and its
      active metabolite, N-desmethyl selumetinib, in patients with NSCLC. A PopPK model
      using data from seven phase 1 studies was first developed and served as prior
      information for the development of the patient PopPK model. The pharmacokinetics
      (PK) of selumetinib and N-desmethyl selumetinib were modeled simultaneously. A
      two-compartment model with zero-first order absorption and first-order
      elimination reasonably described the selumetinib PK. The N-desmethyl metabolite
      of selumetinib was described by a one-compartment model with first-order
      elimination. The final PK parameter estimates were similar between patients with
      NSCLC and patients in the phase 1 population. Selumetinib apparent clearance and
      central volume of distribution were 11.9 L/h and 32.1 L, respectively, in
      patients. Individual selumetinib exposure metrics were estimated to investigate
      the correlation between exposure and efficacy/safety endpoints observed in NSCLC
      studies. There was no significant difference in progression-free survival (the
      primary endpoint) among the different quartiles of exposure. Similarly, no
      significant correlation was observed between selumetinib exposure and other
      secondary efficacy or safety endpoints. The conclusions are in accordance with
      the reported clinical findings.

PMID- 30102414
TI  - Quantitative accuracy of CT numbers: Theoretical analyses and experimental
      studies.
AB  - PURPOSE: The CT number accuracy, that is, CT number bias, plays an important role
      in clinical diagnosis. When strategies to reduce radiation dose are discussed, it
      is important to make sure that the CT number bias is controlled within an
      acceptable range. The purpose of this paper was to investigate the dependence of
      CT number bias on radiation dose level and on image contrast (i.e., the
      difference in CT number between the ROI and the background) in Computed
      Tomography (CT). METHODS: A lesion-background model was introduced to
      theoretically study how the CT number bias changes with radiation exposure level
      and with CT number contrast when a simple linear reconstruction algorithm such as
      filtered backprojection (FBP) is used. The theoretical results were validated
      with experimental studies using a benchtop CT system equipped with a photon
      counting detector (XC-HYDRA FX50, XCounter AB, Sweden) and a clinical diagnostic
      MDCT scanner (Discovery CT750 HD, GE Healthcare, Waukesha, WI, USA) equipped with
      an energy-integrating detector. The Catphan phantom (Catphan 600, the Phantom
      Laboratory, Salem, NY, USA) was scanned at different mAs levels and 50 scans were
      performed for each mAs. The bias of CT number was evaluated for each combination
      of mAs and ROIs with different contrast levels. An anthropomorphic phantom (ATOM
      10-year-old phantom, Model 706, CIRS Inc. Norfolk, VA, USA) with much more
      heterogeneous object content was used to test the applicability of the theory to
      the more general image object cases. RESULTS: Both theoretical and experimental
      studies showed that the CT number bias is inversely proportional to the radiation
      exposure level yet linearly dependent on the CT number contrast between the
      lesion and the background, that is,  CONCLUSIONS: The quantitative accuracy of CT
      numbers can be problematic and thus needs some extra attention when radiation
      dose is reduced. In this work, we showed that the bias of the FBP reconstruction
      increases as mAs is reduced; both positive and negative bias can be observed
      depending on the contrast difference between a targeted ROI and its surrounding
      background tissues.

PMID- 30102416
TI  - Protective effect of a novel sigma-1 receptor agonist is associated with reduced
      endoplasmic reticulum stress in stroke male mice.
AB  - Sigma-1 receptor (Sig-1R) is expressed at endoplasmic reticulum (ER) membranes,
      where it regulates a variety of specific physiological functions. However, the
      profile and exact roles of ER stress-related molecules after Sig-1R agonist
      treatment in an in vivo stroke model are largely unknown. The aim of this study
      is to investigate the effect of a novel Sig-1R agonist, aniline derivative
      compound (Comp-AD), on the ER stress response following ischemic stroke. Male
      C57BL/6J mice received transient middle cerebral artery occlusion for 90 min, and
      were then treated with vehicle saline or Comp-AD at reperfusion. At 3 hr, 1 day,
      and 7 days after reperfusion, immunohis- tochemistry was performed for Sig-1R and
      ER stress-related proteins including phospho protein kinase RNA-like endoplasmic
      reticulum kinase (p-PERK), phospho inositol requiring enzyme 1alpha (p-
      IRE1alpha), and activating transcription factor 6 (ATF6). Neurobehavioral
      analysis showed improved functional recovery at 1 day and 7 days after
      reperfusion, and the infarct volume was significantly smaller at 7 days (p <
      .05), in the Comp-AD group compared with the vehicle group. Comp-AD treatment
      upregulated Sig-1R immunoreactivity at 3 hr and 1 day (p < .05), and reduced p
      PERK and p-IRE1alpha expression at 1 day (p < .05, respectively), in the peri
      ischemic region compared with the vehicle group. Treatment with the novel Sig-1R
      agonist Comp-AD was neuroprotective after transient middle cerebral artery
      occlusion, and was associated with upregulation of Sig-1R and a reduction of ER
      stress.

PMID- 30102415
TI  - Alcohol Outlets, Neighborhood Retail Environments, and Pedestrian Injury Risk.
AB  - BACKGROUND: Alcohol outlet density has been associated with increased pedestrian
      injury risk. It is unclear whether this is because alcohol outlets are located in
      dense retail areas with heavy pedestrian traffic or whether alcohol outlets
      contribute a unique neighborhood risk. We aimed to compare the pedestrian injury
      rate around alcohol outlets to the rate around other, similar retail outlets that
      do not sell alcohol. METHODS: A spatial analysis was conducted on census block
      groups in Baltimore City. Data included pedestrian injury emergency medical
      services (EMS) records from January 1, 2014 to April 15, 2015 (n = 848);
      locations of alcohol outlets licensed for off-premise (n = 726) and on-premise
      consumption (n = 531); and corner (n = 398) and convenience stores (n = 192) that
      do not sell alcohol. Negative binomial regression was used to determine the
      relationship between retail outlet count and pedestrian injuries, controlling for
      key confounding variables. Spatial autocorrelation was also assessed and variable
      selection adjusted accordingly. RESULTS: Each additional off-premise alcohol
      outlet was associated with a 12.3% increase in the rate of neighborhood
      pedestrian injury when controlling for convenience and corner stores and other
      confounders (incidence rate ratio [IRR] = 1.123, 95% confidence interval [CI] =
      1.065, 1.184, p < 0.001). The attributable risk was 4.9% (95% CI = 0.3, 8.9) or
      41 additional injuries. On-premise alcohol outlets were not significant
      predictors of neighborhood pedestrian injury rate in multivariable models (IRR =
      0.972, 95% CI = 0.940, 1.004, p = 0.194). CONCLUSIONS: Off-premise alcohol
      outlets are associated with pedestrian injury rate, even when controlling for
      other types of retail outlets. Findings reinforce the importance of alcohol
      outlets in understanding neighborhood pedestrian injury risk and may provide
      evidence for informing policy on liquor store licensing, zoning, and enforcement.

PMID- 30102417
TI  - Pathophysiology and aetiology of hypoglycaemic crises.
AB  - Hypoglycaemia is a common, life-threatening complication that occurs as a
      component of a wide variety of disease processes. Despite its frequent
      occurrence, information concerning the aetiology, characteristics and outcomes of
      hypoglycaemic crises in veterinary medicine is limited. This review summarises
      the current understanding of the pathophysiology of hypoglycaemia, the body's
      counter-regulatory response, underlying aetiologies, diagnosis and treatment.
      Disease mechanisms are discussed and published evidence in veterinary literature
      regarding prognostic indicators, prevalence, diagnosis and treatment is examined
      for hypoglycaemia-related disease processes including insulinoma, glucose
      lowering toxins and medications.

PMID- 30102418
TI  - Long-term outcome of primary immune-mediated thrombocytopenia in dogs.
AB  - OBJECTIVES: To determine the incidence of relapse after discharge from the
      hospital in dogs with a diagnosis of presumed primary immune-mediated
      thrombocytopenia, risk factors associated with relapse and whether or not
      indefinite use of immunosuppressive medication influences risk of relapse.
      MATERIALS AND METHODS: Medical records from August 2007 through July 2016 were
      reviewed to identify dogs with a diagnosis of presumed primary immune-mediated
      thrombocytopenia. Data collection included signalment, initial diagnostic tests,
      treatment, incidence of relapse, survival duration and follow-up testing.
      RESULTS: A total of 45 dogs were diagnosed, treated and monitored for at least
      one year for presumed primary immune-mediated thrombocytopenia. 89?6% of patients
      survived to discharge and 31% of those experienced a relapse following discharge.
      The median time from diagnosis to relapse was 79 days. Of dogs that experienced a
      relapse, 50% had at least one further relapse. There was no difference in age,
      body weight, gender, breed, platelet count at presentation, nadir packed cell
      volume during hospitalisation, incidence of melaena or initial treatment between
      the relapsing and non-relapsing groups. In the relapsing group, time to platelet
      recovery was significantly longer and these patients were more likely to have
      received a blood transfusion. CLINICAL SIGNIFICANCE: This study does not provide
      evidence to support the use of long-term immunosuppressive medications to prevent
      relapse. However, the data suggest that patients with more severe disease at the
      time of diagnosis or that have already experienced a relapse should be monitored
      more closely.

PMID- 30102419
TI  - Language Matters: Denying the Existence of the 30-Million-Word Gap Has Serious
      Consequences.
AB  - Sperry, Sperry, and Miller (2018) aim to debunk what is called the 30-million
      word gap by claiming that children from lower income households hear more speech
      than Hart and Risley () reported. We address why the 30-million-word gap should
      not be abandoned, and the importance of retaining focus on the vital ingredient
      to language learning-quality speech directed to children rather than overheard
      speech, the focus of Sperry et al.'s argument. Three issues are addressed:
      Whether there is a language gap; the characteristics of speech that promote
      language development; and the importance of language in school achievement. There
      are serious risks to claims that low-income children, on average, hear
      sufficient, high-quality language relative to peers from higher income homes.

PMID- 30102420
TI  - Updated distribution maps for neotropical bats in the superfamily Noctilionoidea.
AB  - The IUCN provides a spatial database for many species, including terrestrial
      mammals. This database includes shapefiles with taxonomic information and the
      extent of occurrence for each species, and has been used in hundreds of studies
      in ecology, biogeography and conservation. Here we provide updated distribution
      maps that comprise the extent of occurrence of the neotropical bat species in the
      superfamily Noctilionoidea (Mammalia: Chiroptera) after a thorough research of
      new records published between January 2008 and March 2018. The main motivation
      for this update was the inclusion of spatial and climatic variables in explaining
      the ecological and taxonomic diversity of noctilionoid bats. The core of the
      superfamily (246 species distributed in five families out of 250 species) occurs
      in the Neotropics and shows ecological diversity unparalleled among mammals. This
      clade also shows the only evolutionary shift towards higher speciation rates
      within the order Chiroptera. Updating the range maps for these bats resulted in
      the modification of maps of 94 species, and the creation of new maps for 37
      species missing from the IUCN database. From the 94 modified maps, 55 species
      increased their latitudinal range and 38 increased their longitudinal range.
      These modifications did not change the overall extent of occurrence of the clade.
      Altogether, modified and new maps represent 53% of Noctilionoidea. No copyright
      or proprietary restrictions are associated with the use of this data set other
      than citation of this Data Paper.

PMID- 30102421
TI  - Introduction to the Special Section on Children's Subjective Well-Being.
AB  - A notable increase in scientific publications on children's subjective well-being
      has been observed since the beginning of the 21st century. Different factors have
      contributed to this phenomenon, one of the most relevant being the concurrence of
      macrolevel (at the population level) and microlevel (at the individual level)
      perspectives in research on child well-being.

PMID- 30102423
TI  - Longitudinal Continuity in Understanding and Production of Giving-Related
      Behavior From Infancy to Childhood.
AB  - Infants have an early understanding of giving (the transfer of an item by one
      agent to another), but little is known about individual differences in these
      abilities or their developmental outcomes. Here, 9-month-olds (N = 59) showing
      clearer neural processing (Event-related potential, ERP) of a give-me gesture
      also evidenced a stronger reaction (pupil dilation) to an inappropriate response
      to a give-me gesture, and at 2 years were more likely to give in response to a
      give-me gesture. None of the differences in understanding and production of
      giving-related behaviors were associated with other sociocognitive variables
      investigated: language, gaze-following, and nongiving helping. The early
      developmental continuity in understanding and production of giving behavior is
      consistent with the great importance of giving for humans throughout the life
      span.

PMID- 30102422
TI  - The development and validation of a multivariable prognostic model to predict
      foot ulceration in diabetes using a systematic review and individual patient data
      meta-analyses.
AB  - AIMS: Diabetes guidelines recommend screening for the risk of foot ulceration but
      vary substantially in the underlying evidence base. Our purpose was to derive and
      validate a prognostic model of independent risk factors for foot ulceration in
      diabetes using all available individual patient data from cohort studies
      conducted worldwide. METHODS: We conducted a systematic review and meta-analysis
      of individual patient data from 10 cohort studies of risk factors in the
      prediction of foot ulceration in diabetes. Predictors were selected for
      plausibility, availability and low heterogeneity. Logistic regression produced
      adjusted odds ratios (ORs) for foot ulceration by ulceration history,
      monofilament insensitivity, any absent pedal pulse, age, sex and diabetes
      duration. RESULTS: The 10 studies contained data from 16 385 participants. A
      history of foot ulceration produced the largest OR [6.59 (95% CI 2.49 to 17.45)],
      insensitivity to a 10 g monofilament [3.18 (95% CI 2.65 to 3.82)] and any absent
      pedal pulse [1.97 (95% CI 1.62 to 2.39)] were consistently, independently
      predictive. Combining three predictors produced sensitivities between 90.0% (95%
      CI 69.9% to 97.2%) and 95.3% (95% CI 84.5% to 98.7%); the corresponding
      specificities were between 12.1% (95% CI 8.2% to 17.3%) and 63.9% (95% CI 61.1%
      to 66.6%). CONCLUSIONS: This prognostic model of only three risk factors, a
      history of foot ulceration, an inability to feel a 10 g monofilament and the
      absence of any pedal pulse, compares favourably with more complex approaches to
      foot risk assessment recommended in clinical diabetes guidelines.

PMID- 30102424
TI  - Language Does Matter: But There is More to Language Than Vocabulary and Directed
      Speech.
AB  - In response to Golinkoff, Hoff, Rowe, Tamis-LeMonda, and Hirsh-Pasek's (2018)
      commentary, we clarify our goals, outline points of agreement and disagreement
      between our respective positions, and address the inadvertently harmful
      consequences of the word gap claim. We maintain that our study constitutes a
      serious empirical challenge to the word gap. Our findings do not support Hart and
      Risley's claim under their definition of the verbal environment; when more
      expansive definitions were applied, the word gap disappeared. The word gap
      argument focuses attention on supposed deficiencies of low-income and minority
      families, risks defining their children out of the educational game at the very
      outset of their schooling, and compromises efforts to restructure curricula that
      recognize the verbal strengths of all learners.

PMID- 30102426
TI  - Interfacially Polymerized Particles with Heterostructured Nanopores for
      Glycopeptide Separation.
AB  - Porous polymer materials are extensively used for biomolecule separation.
      However, conventional homogeneous porous polymer materials cannot efficiently
      separate specific low-abundance biomolecules from complex samples. Here,
      particles fabricated by emulsion interfacial polymerization featuring
      heterostructured nanopores with tunable size are reported, which can be used to
      realize low-abundance glycopeptide (GP) separation from complex biofluids. The
      heterostructured surface inside the nanopores allows solvent-dependent local
      adsorption of biomolecules onto hydrophilic or hydrophobic regions. Low-abundance
      hydrophilic GPs in complex biofluids can be efficiently separated via the
      hydrophilic region of nanopores in low-polarity solvent after the hydrophobic
      region removes high-abundance hydrophobic proteins and non-glycopeptides in high
      polarity solvent. It is expected that these particles with heterostructured
      nanopores can be used for separation of nucleic acids, saccharides, and proteins,
      and downstream clinical diagnosis.

PMID- 30102425
TI  - CCR-CARESS score for predicting operative mortality in patients with colorectal
      cancer.
AB  - BACKGROUND: The aim of this study was to assess factors associated with outcomes
      after surgery for colorectal cancer and to design and internally validate a
      simple score for predicting perioperative mortality. METHODS: Patients undergoing
      surgery for primary invasive colorectal cancer in 22 centres in Spain between
      June 2010 and December 2012 were included. Clinical variables up to 30 days were
      collected prospectively. Multiple logistic regression techniques were applied and
      a risk score was developed. The Hosmer-Lemeshow test was applied and the area
      under the receiver operating characteristic (ROC) curve (AUC, with 95 per cent
      c.i.) was estimated. RESULTS: A total of 2749 patients with a median age of 68.5
      (range 24-97) years were included; the male : female ratio was approximately 2 :
      1. Stage III tumours were diagnosed in 32.6 per cent and stage IV in 9.5 per
      cent. Open surgery was used in 39.3 per cent, and 3.6 per cent of interventions
      were urgent. Complications were most commonly infectious or surgical, and 25.5
      per cent of patients had a transfusion during the hospital stay. The 30-day
      postoperative mortality rate was 1.9 (95 per cent c.i. 1.4 to 2.4) per cent.
      Predictive factors independently associated with mortality were: age 80 years or
      above (odds ratio (OR) 2.76), chronic obstructive pulmonary disease (COPD) (OR
      3.62) and palliative surgery (OR 10.46). According to the categorical risk score,
      a patient aged 80 years or more, with COPD, and who underwent palliative surgery
      would have a 23.5 per cent risk of death within 30 days of the intervention.
      CONCLUSION: Elderly patients with co-morbidity and palliative intention of
      surgery have an unacceptably high risk of death.

PMID- 30102427
TI  - Abuse Potential of Buprenorphine/Samidorphan Combination Compared to
      Buprenorphine and Placebo: A Phase 1 Randomized Controlled Trial.
AB  - Buprenorphine/samidorphan combination (BUP/SAM) is an opioid system modulator
      being investigated as adjunctive treatment for major depressive disorder. BUP/SAM
      is a fixed-dose combination of buprenorphine, a partial MU-opioid receptor
      agonist and kappa-opioid receptor antagonist, and samidorphan, a MU-opioid
      receptor antagonist added to address the abuse and dependence potential of
      buprenorphine. In this study, we assessed the effect of samidorphan on the abuse
      potential of buprenorphine in the BUP/SAM combination in nondependent,
      recreational, adult opioid users (ClinicalTrials.gov ID: NCT02413281).
      Participants were randomized to 6 treatments in a blinded, Williams crossover
      design: placebo, BUP/SAM at the intended therapeutic dose (2 mg/2 mg), at 4-fold
      (8 mg/8 mg) and 8-fold (16 mg/16 mg) the therapeutic dose, and buprenorphine
      alone (8 mg and 16 mg). The primary end point was maximum effect (Emax ) on the
      visual analog scale for "at the moment" Drug Liking. Emax of Drug Liking for the
      BUP/SAM 2 mg/2 mg dose was similar to that for placebo (median within-subject
      difference [90% confidence interval]: 2.5 [0.0-9.0]). The supratherapeutic doses
      of BUP/SAM showed differences of small magnitude on Drug Liking Emax compared to
      placebo. Drug Liking Emax for all BUP/SAM doses were significantly lower than
      those observed for either buprenorphine dose alone. Fewer participants reported
      adverse events associated with abuse potential with BUP/SAM than with
      buprenorphine alone, and the overall safety profile of BUP/SAM was consistent
      with prior reports in healthy volunteers. These findings indicate that
      samidorphan substantially reduces the abuse potential of buprenorphine in the
      BUP/SAM combination.

PMID- 30102429
TI  - Early Childhood Parenting Predicts Late Childhood Brain Functional Connectivity
      During Emotion Perception and Reward Processing.
AB  - Seventy-nine 3-year olds and their mothers participated in a laboratory-based
      task to assess maternal hostility. Mothers also reported their behavioral
      regulation of their child. Seven years later, functional magnetic resonance
      imaging data were acquired while viewing emotional faces and completing a reward
      processing task. Maternal hostility predicted more negative amygdala connectivity
      during exposure to sad relative to neutral faces with frontal and parietal
      regions as well as more negative left ventral striatal connectivity during
      monetary gain relative to loss feedback with the right posterior orbital frontal
      cortex and right inferior frontal gyrus. In contrast, maternal regulation
      predicted enhanced cingulo-frontal connectivity during monetary gain relative to
      loss feedback. Results suggest parenting is associated with alterations in
      emotion and reward processing circuitry 7-8 years later.

PMID- 30102430
TI  - Hyperpolarized 3 He MRI Ventilatory Apparent Diffusion Coefficient of Alpha-1
      Antitrypsin Deficiency.

PMID- 30102428
TI  - Hospitalisation in short-stay units for adults with internal medicine diseases
      and conditions.
AB  - BACKGROUND: Short-stay units are hospital units that provide short-term care for
      selected patients. Studies have indicated that short-stay units might reduce
      admission rates, time of hospital stays, hospital readmissions and expenditure
      without compromising the quality of care. Short-stay units are often defined by a
      target patient category, a target function, and a target time frame.
      Hypothetically, short-stay units could be established as part of any department,
      but this review focuses on short-stay units that provide care for participants
      with internal medicine diseases and conditions. OBJECTIVES: To assess beneficial
      and harmful effects of short-stay unit hospitalisation compared with usual care
      in people with internal medicine diseases and conditions. SEARCH METHODS: We
      searched CENTRAL, MEDLINE, Embase, three other databases and two trials registers
      up to 13 December 2017 together with reference checking, citation searching and
      contact with study authors to identify additional studies. We also searched
      several grey literature sources and performed a forward citation search for
      included studies. SELECTION CRITERIA: We included randomised trials and cluster
      randomised trials, comparing hospitalisation in a short-stay unit with usual care
      (hospitalisation in a traditional hospital ward or other services). We defined a
      short-stay unit to be a hospital ward where the targeted length of stay in
      hospital for patients was five days or less. We included both multipurpose and
      specialised short-stay units. Participants were adults admitted to hospital with
      an internal medicine disease or condition. We excluded surgical, obstetric,
      psychiatric, gynaecological, and ambulatory participants. Trials were included
      irrespective of publication status, date, and language. DATA COLLECTION AND
      ANALYSIS: We used standard methodological procedures expected by Cochrane. Two
      review authors independently extracted data and assessed the risk of bias of each
      included trial. We measured intervention effect sizes by meta-analyses for two
      primary outcomes, mortality and serious adverse events, and one secondary
      outcome, hospital readmission. We narratively reported the following important
      outcomes: quality of life, activities of daily living, non-serious adverse
      events, and costs. We used risk ratio differences of 15% for mortality and of 20%
      for serious adverse events for minimal relevant clinical consideration. We rated
      the certainty of the evidence and the strength of recommendations of the outcomes
      using the GRADE approach. MAIN RESULTS: We included 19 records reporting on 14
      randomised trials with a total of 2872 participants. One trial was ongoing.
      Thirteen trials evaluated short-stay unit hospitalisation for six specific
      conditions (acute decompensated heart failure (one trial), asthma (one trial),
      atrial fibrillation (one trial), chest pain (seven trials), syncope (two trials),
      and transient ischaemic attack (one trial)) and one trial investigated
      participants presenting with miscellaneous internal medicine disease and
      conditions. The components of the intervention differed among the trials as
      dictated by the trial participants' condition. All included trials were at high
      risk of bias.The certainty of the evidence for all outcomes was very low.
      Consequently, it is uncertain whether hospitalisation in short-stay units
      compared with usual care reduces mortality (risk ratio (RR) 0.73, 95% confidence
      interval (CI) 0.47 to 1.15) 5 trials (seven additional trials reporting on 1299
      participants reported no deaths in either group)); serious adverse events (RR
      0.95, 95% CI 0.59 to 1.54; 7 trials (one additional trial with 108 participants
      reported no serious adverse events in either group)), and hospital readmission
      (RR 0.80, 95% CI 0.54 to 1.19, 8 trials (one additional trial with 424
      participants did not report results for participants)). There was not enough
      information to confirm or refute that short-stay unit hospitalisation had
      relevant effects on quality of life, activities of daily living, non-serious
      adverse events, and costs. AUTHORS' CONCLUSIONS: Overall, the quantity and the
      certainty of the evidence was very low. Consequently, it is uncertain whether
      there are any beneficial or harmful effects of short-stay unit hospitalisation
      for adults with internal medicine diseases and conditions - more trials comparing
      the effects of short-stay units with usual care are needed. Such trials ought to
      be conducted with low risk of bias and low risks of random errors to improve the
      overall confidence in the evidence.

PMID- 30102432
TI  - Conspicuity of Malignant Liver Tumors on Diffusion-Weighted Imaging With Short
      tau Inversion Recovery After Gadolinium Ethoxybenzyl
      Diethylenetriaminepentaacetic Acid Administration.
AB  - BACKGROUND: Diffusion-weighted imaging (DWI) has been used for the detection and
      characterization of liver tumors because it has excellent contrast resolution.
      DWI using short tau inversion recovery (STIR) can improve tumor-to-liver contrast
      after gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)
      administration that shortens the T1 relaxation of liver parenchyma. PURPOSE: To
      quantitatively and qualitatively compare the conspicuity of malignant liver
      tumors on DWI after Gd-EOB-DTPA administration between STIR and chemical shift
      selective (CHESS) sequences. STUDY TYPE: Single-institution retrospective study.
      SUBJECTS: Fifty-seven patients with histologically confirmed malignant liver
      tumors were evaluated. FIELD STRENGTH/SEQUENCE: Low b-value DWIs with STIR and
      CHESS sequences 18-20 minutes after Gd-EOB-DTPA administration were acquired at
      1.5T. ASSESSMENT: Tumor contrast-to-noise ratio (CNR) and visual grade of tumor
      conspicuity on DWI between STIR and CHESS sequences were compared. STATISTICAL
      TESTS: Paired Student's t-test and the Wilcoxon signed rank-test were applied. P
      < 0.05 was considered statistically significant. RESULTS: The mean tumor CNR and
      visual grade of tumor conspicuity on DWI were significantly higher for STIR than
      for CHESS (both P < 0.001). Regardless of the presence of chronic liver disease,
      the mean CNR (normal liver 33.5 +/- 19.8 vs. 15.7 +/- 12.2, P < 0.001; chronic
      liver disease 19.6 +/- 11.0 vs. 9.2 +/- 7.8, P < 0.001) and the visual
      conspicuity grade (normal liver 3.36 +/- 0.64 vs. 2.56 +/- 0.77, P < 0.001;
      chronic liver disease 2.94 +/- 0.80 vs. 2.25 +/- 0.84, P = 0.001) were
      significantly higher for STIR than for CHESS. Mean CNR and the visual conspicuity
      grade were also significantly higher for STIR than for CHESS in patients with
      hepatocellular carcinomas (CNR 18.1 +/- 10.5 vs. 8.8 +/- 7.2, P < 0.001; visual
      grade 2.88 +/- 0.83 vs. 2.22 +/- 0.87, P = 0.001) or metastases (CNR 35.0 +/-
      19.3 vs. 16.2 +/- 13.1, P < 0.001; visual grade 3.45 +/- 0.51 vs. 2.59 +/- 0.73,
      P < 0.001). DATA CONCLUSION: DWI using STIR may be more helpful for depicting
      malignant liver tumors after Gd-EOB-DTPA administration compared with DWI using
      CHESS. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING
      2018.

PMID- 30102431
TI  - Uteroplacental and Fetal 4D Flow MRI in the Pregnant Rhesus Macaque.
AB  - BACKGROUND: Pregnancy complications are often associated with poor uteroplacental
      vascular adaptation and standard diagnostics are unable to reliably quantify flow
      in all uteroplacental vessels and have poor sensitivity early in gestation.
      PURPOSE: To investigate the feasibility of using 4D flow MRI to assess total
      uteroplacental blood flow in pregnant rhesus macaques as a precursor to human
      studies. STUDY TYPE: Retrospective feasibility study. ANIMAL MODEL: Fifteen
      healthy, pregnant rhesus macaques ranging from the 1st trimester to 3rd trimester
      of gestation. FIELD STRENGTH/SEQUENCE: Abdominal 4D flow MRI was performed on a
      3.0T scanner with a radially undersampled phase contrast (PC) sequence. Reference
      ferumoxytol-enhanced angiograms were acquired with a 3D ultrashort echo time
      sequence with a center-out radial trajectory. ASSESSMENT: Repeatability of flow
      measurements was assessed with scans performed same-day and on consecutive days
      in the uterine arteries and ovarian veins. In-flow was compared against out-flow
      in the uterus, umbilical cord, and fetal heart with a conservation of mass
      analysis. Conspicuity of uteroplacental vessels was qualitatively compared
      between PC angiograms derived from 4D flow data and ferumoxytol-enhanced
      angiograms. STATISTICAL TESTS: Bland-Altman analysis was used to quantify same
      day and consecutive-day repeatability. RESULTS: Same-day flow measurements showed
      an average difference between scans of 13% in both the uterine arteries and
      ovarian veins, while consecutive-day measurements showed average differences of
      22% and 24%, respectively. Comparisons of in-flow and out-flow showed average
      differences of 15% in the uterus, 8% in fetal heart, and 15% in the umbilical
      cord. PC angiograms showed similar depiction of main uteroplacental vessels as
      high-resolution, ferumoxytol-enhanced angiograms. DATA CONCLUSION: 4D flow MRI
      could be used in the rhesus macaque for repeatable flow measurements in the
      uteroplacental and fetal vasculature, setting the stage for future human studies.
      LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018.

PMID- 30102433
TI  - Added Value of sequentially performed gadoxetic acid-enhanced liver MRI for the
      diagnosis of small (10-19 mm) or atypical hepatic observations at contrast
      enhanced CT: A prospective comparison.
AB  - BACKGROUND: Small hepatocellular carcinomas (HCCs) often show atypical features
      at cross-sectional imaging, yet there is no preferred recommendation for the
      diagnosis or characterization of small observations (10-19 mm) at present.
      PURPOSE: To determine the added value of sequentially performed gadoxetic acid
      enhanced liver MRI for contrast-enhanced computed tomography (CECT)-detected
      small (10-19 mm) or atypical hepatic observations >=20 mm in the diagnosis of
      HCC. STUDY TYPE: Prospective, cross-sectional, intraindividual comparison.
      POPULATION: In all, 110 patients at high risk of developing HCC. FIELD
      STRENGTH/SEQUENCE: 1.5T and 3T/T1 -weighted imaging. ASSESSMENT: Hepatic
      observations were classified into HCCs or benign non-HCCs based on imaging
      features of arterial phase hyperenhancement (APHE) and portal or delayed washout
      at CT or APHE and portal washout at MRI. Final diagnoses were established using a
      composite algorithm and diagnostic performances of MRI and CT were compared in
      all observations. In addition, in a subgroup of histologically confirmed
      observations and stable benign observations during follow-up (n = 94),
      sensitivity and specificity of MRI were compared between the aforementioned
      criteria and LR-5 of Liver Imaging Reporting and Data System v2014. STATISTICAL
      TEST: chi2 test. RESULTS: MRI provided higher sensitivity than CT (62.2% vs.
      27.0%, P = 0.0001) while maintaining specificity (97.2%, each) at the per-patient
      level. Among 124 observations, 10-19 mm in size, MRI showed significantly higher
      sensitivity in diagnosing HCCs (62.5%, 50/80) than CT (25%, 20/80, P < 0.0001)
      with comparable specificity (97.7% [43/44], each). However, seven atypical
      observations (>=20 mm) at CT remained atypical at MRI. In the subgroup analysis,
      the diagnostic criteria of APHE and portal washout showed a significantly higher
      sensitivity (44.2%, 19/43) than LR-5 (23.2%, 10/43, P = 0.004), without
      compromising specificity (97.7% vs. 95.5%). DATA CONCLUSION: Sequentially
      performed gadoxetic acid-enhanced MRI provided added value to CECT for the
      diagnosis of HCCs in small observations by improving sensitivity while
      maintaining specificity. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J.
      Magn. Reson. Imaging 2018.

PMID- 30102434
TI  - Diffusion kurtosis imaging in sacroiliitis to evaluate the activity of ankylosing
      spondylitis.
AB  - BACKGROUND: Conventional magnetic resonance (MR) imaging is limited in providing
      sufficient information on microstructure or in quantitatively evaluating certain
      inflammation processes. Functional MR sequences such as diffusion kurtosis
      imaging (DKI) might help to evaluate the sacroiliac joint in ankylosing
      spondylitis (AS) patients. PURPOSE: To explore the application of DKI in
      evaluating the disease activity of AS. STUDY TYPE: Prospective. POPULATION: Forty
      four patients with a diagnosis of AS according to the Assessment in
      SpondyloArthritis International Society (ASAS) criteria. FIELD STRENGTH/SEQUENCE:
      3.0T MRI including the DKI sequence (b = 0, 500, 1000, 1500, 2000 s/mm2 ).
      STATISTICAL TESTS: Two-independent-samples t-test and one-way analysis of
      variance (ANOVA) were used to compare the DKI parameters among different groups,
      and post-hoc Scheffe's method was adopted. Receiver operating characteristic
      (ROC) analysis and Spearman's rank correlation were performed to test the
      diagnostic performance of DKI parameters in distinguishing different activity
      grades and the correlation between them, respectively. ASSESSMENT: AS disease
      activity was evaluated according to the Ankylosing Spondylitis Disease Activity
      Score (ASDAS), and four disease activity states were chosen by consensus:
      inactive disease and moderate, high, and very high disease activity. The three
      cutoffs selected to separate these states were: 1.3, 2.1, and 3.5 units,
      respectively. RESULTS: The corrected ADC (D) and apparent diffusion coefficient
      (ADC) values of sacroiliac joints in the active group were significantly higher,
      while the the kurtosis of diffusion (K value) value was significantly lower than
      those of the inactive group (all P < 0.001). The D value performed best in
      distinguishing different activity grades (all P < 0.001). The D and ADC values
      correlated positively, while the K value correlated negatively, with activity
      grade significantly (r = 0.918, 0.798, and -0.765, respectively; all P < 0.001).
      DATA CONCLUSION: DKI of sacroiliac joints might be useful to evaluate the disease
      activity of AS. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson.
      Imaging 2018.

PMID- 30102435
TI  - Best practices for MRI systematic reviews and meta-analyses.
AB  - : As defined by the Cochrane Collaboration, a systematic review is a review of
      evidence with a clearly formulated question that uses systematic and explicit
      methods to identify, select, and critically appraise relevant primary research,
      and to extract and analyze data from the studies that are included in the review.
      Meta-analysis is a statistical method to combine the results from primary studies
      that accounts for sample size and variability to provide a summary measure of the
      studied outcome. Systematic reviews of diagnostic test accuracy present unique
      methodological and reporting challenges not present in systematic reviews of
      interventions. This review provides guidance and further resources highlighting
      current best practices in methodology and reporting of systematic reviews of
      diagnostic test accuracy, with a specific focus on challenges and opportunities
      for MRI imaging. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson.
      Imaging 2018.

PMID- 30102436
TI  - Renal Functional MRI and Its Application.
AB  - : Renal function varies according to the nature and stage of diseases. Renal
      functional magnetic resonance imaging (fMRI), a technique considered superior to
      the most common method used to estimate the glomerular filtration rate, allows
      for noninvasive, accurate measurements of renal structures and functions in both
      animals and humans. It has become increasingly prevalent in research and clinical
      applications. In recent years, renal fMRI has developed rapidly with progress in
      MRI hardware and emerging postprocessing algorithms. Function-related imaging
      markers can be acquired via renal fMRI, encompassing water molecular diffusion,
      perfusion, and oxygenation. This review focuses on the progression and challenges
      of the main renal fMRI methods, including dynamic contrast-enhanced MRI, blood
      oxygen level-dependent MRI, diffusion-weighted imaging, diffusion tensor imaging,
      arterial spin labeling, fat fraction imaging, and their recent clinical
      applications. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. Magn. Reson.
      Imaging 2018;48:863-881.

PMID- 30102437
TI  - Investigating the Thermal Stability of Organic Thin-Film Transistors and
      Phototransistors Based on [1]-Benzothieno-[3,2-b]-[1]-benzothiophene Dimeric
      Derivatives.
AB  - Two new highly thermally stable [1]benzothieno[3,2-b][1]benzothiophene (BTBT)
      dimeric derivatives, namely 1,4-bis([1]benzothieno[3,2-b][1]benzothiophene-2
      yl)benzene (BTBT-Ph-BTBT) and 4,4'-bis([1]benzothieno[3,2-b][1]benzothiophene-2
      yl)-1,1'-biphenyl (BTBT-DPh-BTBT), were synthesized by combining two simple
      fragment structures. Compared to the monomer compound 2-phenyl[1]benzothieno[3,2
      b][1]benzothiophene (Ph-BTBT, MUmax =3.4*10-2  cm2  V-1  s-1 ), the organic thin
      film transistors (OTFTs) based on BTBT-Ph-BTBT and BTBT-DPh-BTBT showed
      significantly higher mobility (up to 2.5 and 3.6 cm2  V-1  s-1 for BTBT-Ph-BTBT
      and BTBT-DPh-BTBT, respectively). The mobility of OTFTs based on BTBT-Ph-BTBT was
      kept at a high value (2.4*10-1  cm2  V-1  s-1 ) after the devices were thermally
      annealed at 350  degrees C. Furthermore, the organic phototransistors (OPTs)
      based on BTBT-Ph-BTBT and BTBT-DPh-BTBT displayed high photosensitivities in a
      range of 250-400 nm with a low intensity, making these materials potentially
      applicable for sensitive optoelectronic devices.

PMID- 30102438
TI  - Radiomic Signature as a Predictive Factor for Lymph Node Metastasis in Early
      Stage Cervical Cancer.
AB  - BACKGROUND: Lymph node metastasis (LNM) is the principal risk factor for poor
      outcomes in early-stage cervical cancer. Radiomics may offer a noninvasive way
      for predicting the stage of LNM. PURPOSE: To evaluate a radiomic signature of LN
      involvement based on sagittal T1 contrast-enhanced (CE) and T2 MRI sequences.
      STUDY TYPE: Retrospective. POPULATION: In all, 143 patients were randomly divided
      into two primary and validation cohorts with 100 patients in the primary cohort
      and 43 patients in the validation cohort. FIELD STRENGTH/SEQUENCE: T1 CE and T2
      MRI sequences at 3T. ASSESSMENT: The gold standard of LN status was based on
      histologic results. A radiologist with 10 years of experience used the ITK-SNAP
      software for 3D manual segmentation. A senior radiologist with 15 years of
      experience validated all segmentations. The area under the receiver operating
      characteristics curve (ROC AUC), classification accuracy, sensitivity, and
      specificity were used between LNM and non-LNM groups. STATISTICAL TESTS: A total
      of 970 radiomic features and seven clinical characteristics were extracted.
      Minimum redundancy / maximum relevance and support vector machine algorithms were
      applied to select features and construct a radiomic signature. The Mann-Whitney U
      test and the chi-square test were used to test the performance of clinical
      characteristics and potential prognostic outcomes. The results were used to
      assess the quantitative discrimination performance of the SVM-based radiomic
      signature. RESULTS: The radiomic signatures allowed good discrimination between
      LNM and non-LNM groups. The ROC AUC was 0.753 (95% confidence interval [CI],
      0.656-0.850) in the primary cohort and 0.754 (95% CI, 0584-0.924) in the
      validation cohort. DATA CONCLUSIONS: A multiple-sequence MRI radiomic signature
      can be used as a noninvasive biomarker for preoperative assessment of LN status
      and potentially influence the therapeutic decision-making in early-stage cervical
      cancer patients. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON.
      IMAGING 2018.

PMID- 30102439
TI  - Characterization of proliferative, glial and angiogenic responses after a CoCl2 
      induced injury of photoreceptor cells in the adult zebrafish retina.
AB  - The adult zebrafish is considered a useful model for studying mechanisms involved
      in tissue growth and regeneration. We have characterized cytotoxic damage to the
      retina of adult zebrafish caused by the injection of cobalt chloride (CoCl2 )
      into the vitreous cavity. The CoCl2 concentration we used primarily caused injury
      to photoreceptors. We observed the complete disappearance of cones, followed by
      rods, across the retina surface from 28 to 96 hr after CoCl2 injury. The loss of
      30% of bipolar cells was also observed by 50 hr after lesion (hpl). CoCl2 injury
      provoked a strong induction of the proliferative activity of multipotent Muller
      glia and derived progenitors. The effect of CoCl2 on retina cells was
      significantly reduced by treatment with glutamate ionotropic receptor
      antagonists. Cone photoreceptor regeneration occurred 25 days after injury.
      Moreover, a single dose of CoCl2 induced vascular damage and regeneration,
      whereas three injections of CoCl2 administered weekly provoked neovascular-like
      changes 20 days after injury. CoCl2 injury also caused microglial reactivity in
      the optic disc, retina periphery and fibre layer. CoCl2 -induced damage enhanced
      pluripotency and proneural transcription factor gene expression in the mature
      retina 72 hpl. Tumour necrosis factor alpha, vascular endothelial growth factor
      (VEGF) and VEGF receptor mRNA levels were also significantly enhanced by 72 hpl.
      The injury paradigm we have described in this work may be useful for the
      discovery of signalling molecules and pathways that participate in the
      regenerative response and it may serve as a model to screen for compounds that
      could potentially treat aberrant angiogenesis.

PMID- 30102440
TI  - Alpha-Synuclein Modulates the Physical Properties of DNA.
AB  - Fundamental research on Parkinson's disease (PD) most often focuses on the
      ability of alpha-synuclein (aS) to form oligomers and amyloids, and how such
      species promote brain cell death. However, there are indications that aS also
      plays a gene-regulatory role in the cell nucleus. Here, the interaction between
      monomeric aS and DNA in vitro has been investigated with single-molecule
      techniques. Using a nanofluidic channel system, it was discovered that aS binds
      to DNA and by studying the DNA-protein complexes at different confinements we
      determined that aS binding increases the persistence length of DNA from 70 to 90
      nm at high coverage. By atomic force microscopy it was revealed that at low
      protein-to-DNA ratio, the aS binding occurs as small protein clusters scattered
      along the DNA; at high protein-to-DNA ratio, the DNA is fully covered by protein.
      As DNA-aS interactions may play roles in PD, it is of importance to characterize
      biophysical properties of such complexes in detail.

PMID- 30102441
TI  - Preoperative tumor texture analysis on MRI predicts high-risk disease and reduced
      survival in endometrial cancer.
AB  - BACKGROUND: Improved methods for preoperative risk stratification in endometrial
      cancer are highly requested by gynecologists. Texture analysis is a method for
      quantification of heterogeneity in images, increasingly reported as a promising
      diagnostic tool in various cancer types, but largely unexplored in endometrial
      cancer. PURPOSE: To explore whether tumor texture parameters from preoperative
      MRI are related to known prognostic features (deep myometrial invasion, cervical
      stroma invasion, lymph node metastases, and high-risk histological subtype) and
      to outcome in endometrial cancer patients. STUDY TYPE: Prospective cohort study.
      POPULATION/SUBJECTS: In all, 180 patients with endometrial carcinoma were
      included from April 2009 to November 2013 and studied until January 2017. FIELD
      STRENGTH/SEQUENCES: Preoperative pelvic MRI including contrast-enhanced T1 
      weighted (T1 c), T2 -weighted, and diffusion-weighted imaging at 1.5T.
      ASSESSMENT: Tumor regions of interest (ROIs) were manually drawn on the slice
      displaying the largest cross-sectional tumor area, using the proprietary research
      software TexRAD for analysis. With a filtration-histogram technique, the texture
      parameters standard deviation, entropy, mean of positive pixels (MPP), skewness,
      and kurtosis were calculated. STATISTICAL TESTS: Associations between texture
      parameters and histological features were assessed by uni- and multivariable
      logistic regression, including models adjusting for preoperative biopsy status
      and conventional MRI findings. Multivariable Cox regression analysis was used for
      survival analysis. RESULTS: High tumor entropy in apparent diffusion coefficient
      (ADC) maps independently predicted deep myometrial invasion (odds ratio [OR] 3.2,
      P lt  0.001), and high MPP in T1 c images independently predicted high-risk
      histological subtype (OR 1.01, P = 0.004). High kurtosis in T1 c images predicted
      reduced recurrence- and progression-free survival (hazard ratio [HR] 1.5, P lt 
      0.001) after adjusting for MRI-measured tumor volume and histological risk at
      biopsy. DATA CONCLUSION: MRI-derived tumor texture parameters independently
      predicted deep myometrial invasion, high-risk histological subtype, and reduced
      survival in endometrial carcinomas, and thus, represent promising imaging
      biomarkers providing a more refined preoperative risk assessment that may
      ultimately enable better tailored treatment strategies in endometrial cancer.
      LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging
      2018;48:1637-1647.

PMID- 30102443
TI  - Age-Related Changes of Shape and Flow Dynamics in Healthy Adult Aortas: A 4D Flow
      MRI Study.
AB  - BACKGROUND: Abnormal flow dynamics play an early and causative role in pathologic
      changes of the ascending aorta. PURPOSE: To identify: 1) the changes in flow,
      shape, and size that occur in the ascending aorta with normal human ageing and 2)
      the influence of these factors on aortic flow dynamics. STUDY TYPE:
      Retrospective. SUBJECTS: In all, 247 subjects (age range 19-86 years, mean 49 +/-
      17.7, 169 males) free of aortic or aortic valve pathology were included in this
      study. Subjects were stratified by youngest (18-33 years; n = 64), highest (>60
      years, n = 67), and the middle two quartiles (34-60 years, n = 116). FIELD
      STRENGTH/SEQUENCE: Subjects underwent a cardiac MRI (3T) exam including 4D-flow
      MRI of the aorta. ASSESSMENT: Aortic curvature, arch shape, ascending aortic
      angle, ascending aortic diameter, and the stroke volume normalized by the aortic
      volume (nSV) were measured. Velocity, vorticity, and helicity were quantified
      across the thoracic aorta. STATISTICAL TESTS: Univariate and multivariate
      regressions were used to quantify continuous relationships between variables.
      RESULTS: Aortic diameter, ascending aortic angle, shape, and curvature all
      increased across age while nSV decreased (all P < 0.0001). Systolic vorticity in
      the mid arch decreased by 50% across the age range (P < 0.0001), while peak
      helicity decreased by 80% (P < 0.0001). Curvature tightly governs optimal flow in
      the youngest quartile, with an effect size 1.5 to 4 times larger than other
      parameters in the descending aorta, but had a minimal influence with advancing
      age. In the upper quartile of age, flow dynamics were almost completely
      determined by nSV, exerting an effect size on velocity and vorticity >10 times
      that of diameter and other shape factors. DATA CONCLUSION: Aortic shape
      influences flow dynamics in younger subjects. Flow conditions become increasingly
      disturbed with advancing age, and in these conditions nSV has a more dominant
      effect on flow patterns than shape factors. LEVEL OF EVIDENCE: 3 Technical
      Efficacy: Stage 1 Stage 1 J. Magn. Reson. Imaging 2018.

PMID- 30102442
TI  - Predeployment predictors of psychiatric disorder-symptoms and interpersonal
      violence during combat deployment.
AB  - BACKGROUND: Preventing suicides, mental disorders, and noncombat-related
      interpersonal violence during deployment are priorities of the US Army. We used
      predeployment survey and administrative data to develop actuarial models to
      identify soldiers at high risk of these outcomes during combat deployment.
      METHODS: The models were developed in the Army Study to Assess Risk and
      Resilience in Servicemembers (Army STARRS) Pre-Post Deployment Study, a panel
      study of soldiers deployed to Afghanistan in 2012-2013. Soldiers completed self
      administered questionnaires before deployment and one (T1), three (T2), and nine
      months (T3) after deployment, and consented to administrative data linkage. Seven
      during-deployment outcomes were operationalized using the postdeployment surveys.
      Two overlapping samples were used because some outcomes were assessed at T1 (n =
      7,048) and others at T2-T3 (n = 7,081). Ensemble machine learning was used to
      develop a model for each outcome from 273 predeployment predictors, which were
      compared to simple logistic regression models. RESULTS: The relative improvement
      in area under the receiver operating characteristic curve (AUC) obtained by
      machine learning compared to the logistic models ranged from 1.11 (major
      depression) to 1.83 (suicidality).The best-performing machine learning models
      were for major depression (AUC = 0.88), suicidality (0.86), and generalized
      anxiety disorder (0.85). Roughly 40% of these outcomes occurred among the 5% of
      soldiers with highest predicted risk. CONCLUSIONS: Actuarial models could be used
      to identify high risk soldiers either for exclusion from deployment or preventive
      interventions. However, the ultimate value of this approach depends on the
      associated costs, competing risks (e.g. stigma), and the effectiveness to-be
      determined interventions.

PMID- 30102444
TI  - Catalytic Arylhydroxylation of Dehydroalanine in Continuous Flow for Simple
      Access to Unnatural Amino Acids.
AB  - This report discloses the first example of catalytic arylhydroxylation of
      dehydroalanine with aryldiazonium salts. Aryldiazonium salts, which are generated
      from aniline precursors under partially aqueous conditions in continuous flow,
      efficiently reacted with dehydroalanine in the presence of 10-15 mol % ferrocene
      to furnish alpha-hydroxyarylalanine derivatives (up to 82 % yield). The reactions
      proceeded with regioselectivity, broad functional group tolerance, and without
      polymerization of the dehydroalanine. Furthermore, the products were used to
      access alpha-unnatural amino acids, important targets with application in drug
      development.

PMID- 30102445
TI  - Agreement between self and psychiatrist reporting of suicidal ideation at a
      Veterans Administration psychiatric emergency clinic.
AB  - BACKGROUND: With suicide rising in the United States, identifying and preventing
      suicides is increasingly important. To provide a valuable step toward achieving
      effective suicide risk assessment, this study examines the agreement between self
      report measures and psychiatrist documentation of suicidal ideation and behaviors
      (SI) at a Veterans Administration (VA) psychiatric emergency clinic. METHODS: A
      total of 377 veterans presenting at a VA psychiatric emergency clinic completed a
      self-report survey on SI and other acute risk factors for suicidal behavior. We
      examined agreement between veterans' self-reported SI and psychiatrists' clinical
      notes regarding SI. RESULTS: A total of 199 veterans (53%) self-reported SI; 80
      psychiatrist notes (21%) indicated SI. Psychiatrists and veterans differed in 44%
      (164/377) of cases. Among the discordant cases, the veterans' self-report was
      more severe than the psychiatrists' in 97% of cases. Of the 120 veterans with SI
      and documented as having no SI by psychiatrists, 31 (26%) reported having a
      suicide plan and 18 (15%) plan preparations. Findings were similar when
      controlling for presenting problem, current depression, presence of a
      standardized suicide risk assessment, psychiatrist training level, past suicide
      attempt, homelessness, diagnosis of personality, or substance use disorder.
      CONCLUSIONS: Agreement between veterans' self-reports and psychiatrists'
      documentation of SI was generally low, with veterans self-reporting SI
      significantly more often than psychiatrists documented SI in their clinical
      notes. This suggests that inclusion of a self-report questionnaire provides an
      additional source of data to complement information gleaned from the clinical
      interview for a more comprehensive risk assessment, but only if actually examined
      by the clinician.

PMID- 30102446
TI  - Inhibition of Experimental Tinnitus With High Frequency Stimulation of the Rat
      Medial Geniculate Body.
AB  - BACKGROUND: Neuromodulation is a promising treatment modality for tinnitus,
      especially in chronic and severe cases. The auditory thalamus plays a key role in
      the pathophysiology of tinnitus, as it integrates and processes auditory and
      limbic information. OBJECTIVE: The effect of high frequency stimulation and low
      frequency stimulation of the medial geniculate bodies on tinnitus in a noise
      induced tinnitus rat model is assessed. MATERIALS AND METHODS: Presence of
      tinnitus was verified using the gap-induced prepulse inhibition of the acoustic
      startle response paradigm. Hearing thresholds were determined before and after
      noise trauma with auditory brainstem responses. Anxiety-related side-effects were
      evaluated in the elevated zero maze and open field. RESULTS: Results show
      tinnitus development after noise exposure and preserved hearing thresholds of the
      ear that was protected from noise trauma. We found that high frequency
      stimulation of the medial geniculate bodies suppressed tinnitus. This effect
      maintained directly after stimulation when the stimulator was turned off. Low
      frequency stimulation did not have any effects on the gap:no-gap ratio of the
      acoustic startle response. CONCLUSION: High frequency stimulation of the MGB has
      a direct and residual suppressing effect on tinnitus in this animal model. Low
      frequency stimulation of the MGB did not inhibit tinnitus.

PMID- 30102447
TI  - Delayed gadolinium-enhanced MRI of menisci and cartilage (dGEMRIM/dGEMRIC) in
      obese patients with knee osteoarthritis: Cross-sectional study of 85 obese
      patients with intra-articular administered gadolinium contrast.
AB  - BACKGROUND: Early cartilage changes in knee osteoarthritis (OA) can be assessed
      by both intravenous (i.v.) and intra-articular (i.a.) delayed gadolinium-enhanced
      MRI of cartilage (dGEMRIC). PURPOSE: To examine the relationship between i.a.
      dGEMRIC and delayed gadolinium-enhanced MRI of menisci (dGEMRIM), and to
      investigate if the approach can be used to assess the morphological degeneration
      of menisci in obese patients with knee OA. STUDY TYPE: Cross-sectional.
      POPULATION: Eighty-five obese patients with knee OA. FIELD STRENGTH/SEQUENCES:
      1.5T. Inversion recovery sequence with four inversion times. ASSESSMENT: T1
      relaxation times were calculated for posterior weight-bearing femoral cartilage
      and the posterior horns of the menisci. Meniscus degeneration sum score (0-2) was
      assessed as increased signal/no signal (1/0) and tear/no tear (1/0). STATISTICAL
      TESTS: T1 relaxation times were compared using Student's t-test. Comparison of
      cartilage and meniscus T1 relaxation times was done by regression analysis.
      Analysis of variance (ANOVA) was used for comparison of meniscal T1 relaxation
      times among the three summed morphological scores (0-2). Statistical analyses
      were performed with a level of significance at 0.05. RESULTS: For lateral
      menisci, morphology sum scores of 0, 1, and 2 were found in 13, 58, and 14
      patients and for medial menisci in 2, 30, and 30 patients, respectively. Mean T1
      relaxation times were 441 msec, 480 msec, and 497 msec for cartilage, lateral
      menisci, and medial menisci, respectively. T1 relaxation times for the menisci
      were similar (P = 0.53), and a weak correlation was found between dGEMRIC and
      dGEMRIM in the lateral compartments (R = 0.26). Comparing dGEMRIM between
      different morphology sum scores showed no differences (P > 0.4). DATA CONCLUSION:
      I.a. dGEMRIM showed no correlation between the degree of meniscal degeneration
      and meniscus T1 relaxation times. I.a. dGEMRIM do not seem to deliver useful
      information about meniscus degeneration to be suitable for clinical applications,
      but i.a. dGEMRIC may still be considered an alternative contrast-saving method
      for cartilage. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson.
      Imaging 2018;48:1700-1706.

PMID- 30102448
TI  - Colorimetric Carbonyl Sulfide (COS)/Hydrogen Sulfide (H2 S) Donation from gamma
      Ketothiocarbamate Donor Motifs.
AB  - Hydrogen sulfide (H2 S) is a biologically active molecule that exhibits
      protective effects in a variety of physiological and pathological processes.
      Although several H2 S-related biological effects have been discovered by using H2
      S donors, knowing how much H2 S has been released from donors under different
      conditions remains challenging. Now, a series of gamma-ketothiocarbamate (gamma
      KetoTCM) compounds that provide the first examples of colorimetric H2 S donors
      and enable direct quantification of H2 S release, were reported. These compounds
      are activated through a pH-dependent deprotonation/beta-elimination sequence to
      release carbonyl sulfide (COS), which is quickly converted into H2 S by carbonic
      anhydrase. The p-nitroaniline released upon donor activation provides an optical
      readout that correlates directly to COS/H2 S release, thus enabling colorimetric
      measurement of H2 S donation.

PMID- 30102450
TI  - Biobased Benzoxazine Derived from Daidzein and Furfurylamine: Microwave-Assisted
      Synthesis and Thermal Properties Investigation.
AB  - A biobased benzoxazine resin (Dz-f) demonstrating excellent thermal properties
      was synthesized from daidzein and furfurylamine by using a microwave heating
      method. The chemical structure of synthesized benzoxazine monomer was identified
      by FTIR and NMR (1 H and 13 C NMR) before it was cured and its thermal properties
      evaluated by differential scanning calorimetry (DSC), TGA, and dynamic mechanical
      analysis (DMA). The cured resin p(Dz-f) exhibited a glass transition temperature
      (Tg ) of 391  degrees C, a very high char yield of 68.7 %, and outstanding
      thermal stability; the Tg value obtained was the highest thermal stability value
      ever reported for polybenzoxazine with a high biobased content. Moreover, Dz-f
      demonstrated a satisfying processability, which was rare for the high-performance
      thermosetting resins. This work provided us with a new strategy for the
      preparation of high biocontent resins with excellent thermal properties. In
      addition, the combination of biobased feedstocks with a microwave-assisted
      heating method as well as the potential application of this approach in high-end
      fields might perpetuate remarkable progress towards the sustainable development
      of the polymeric industry.

PMID- 30102449
TI  - Prospective comparison between DCE-MRR and 99m Tc-DTPA-based SPECT for
      determination of allograft renal function.
AB  - BACKGROUND: Glomerular filtration rate (GFR) is a preferred indicator of
      allograft renal function, but direct measurement of GFR remains complicated.
      PURPOSE: To prospectively compare dynamic contrast-enhanced MR renography (DCE
      MRR) with 99m Tc-DTPA-based single-photon emission computed tomography (SPECT)
      for determination of allograft renal function. STUDY TYPE: Prospective.
      POPULATION: Seventy kidney-transplant recipients FIELD STRENGTH: A low-dose DCE
      MRR with a 3.0T scanner and a 99m Tc-DTPA-based SPECT after renal transplantation
      were performed. ASSESSMENT: A Baumann-Rudin (BR) and a modified two-compartment
      model (JZ2C) were used for DCE-MRR analysis. Standard Gate's method was used for
      SPECT analysis. An endogenous creatinine clearance rate (CCr) constituted the
      reference standard. STATISTICAL TESTS: Pearson correlation test and Bland-Altman
      agreement analysis. RESULTS: The reference CCr-GFR was 59.58 +/- 23.72
      mL/min/1.73 m2 . GFR determined by eGFR, BR, JZ2C, and SPECT was 90.22 +/- 34.38,
      36.78 +/- 14.46, 48.99 +/- 23.88, and 67.32 +/- 18.44 mL/min/1.73 m2 ,
      respectively. DCE-MRR using JZ2C had the best overall performance, with a Pearson
      correlation coefficient of 0.81, a bias of -10.58 mL/min/1.73 m2 , and a
      precision of 14.61 mL/min/1.73 m2 , as well as high accuracy (30-50% intervals:
      74.3-90.0%). Although SPECT had a small bias (7.74 mL/min/1.73 m2 ), it had a
      poor correlation coefficient (0.38), poor precision (23.93 mL/min/1.73 m2 ), and
      low accuracy (64.3-72.3%) as compared with DCE-MRR using JZ2C. DATA CONCLUSION:
      DCE-MRR using JZ2C is superior to 99m Tc-DTPA-based SPECT to determine allograft
      renal function. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson.
      Imaging 2018.

PMID- 30102451
TI  - Synthesis and Biological Evaluation of Reniochalistatins A-E and a
      Reniochalistatin E Analogue.
AB  - The total synthesis of reniochalistatins A-E, along with a reniochalistatin E
      analogue (inverso-E) was successfully achieved through Fmoc-based solid-phase
      peptide synthesis and subsequent macrolactamization with PyBOP and DIEA. The
      biological activities of these reniochalistatins and a key linear peptide
      intermediate were systematically evaluated. Among these seven synthesized
      compounds, linear reniochalistatin B was found to have potent activity against
      several cancer cell lines not shown by the cyclic reniochalistatin B counterpart.
      In addition, linear reniochalistatin B was found to have antitubercular activity
      (IC50 =1.4 MUm). Inverso-E possesses increasing cytotoxicity against the HeLa and
      LNCaP cell lines after simple alternation of the sequence of amino acids in
      reniochalistatin E. The results of these studies provide a feasible method to
      further investigate the structure-activity relationships (SARs) of
      reniochalistatins A-E.

PMID- 30102452
TI  - Valleytronics: Opportunities, Challenges, and Paths Forward.
AB  - A lack of inversion symmetry coupled with the presence of time-reversal symmetry
      endows 2D transition metal dichalcogenides with individually addressable valleys
      in momentum space at the K and K' points in the first Brillouin zone. This valley
      addressability opens up the possibility of using the momentum state of electrons,
      holes, or excitons as a completely new paradigm in information processing. The
      opportunities and challenges associated with manipulation of the valley degree of
      freedom for practical quantum and classical information processing applications
      were analyzed during the 2017 Workshop on Valleytronic Materials, Architectures,
      and Devices; this Review presents the major findings of the workshop.

PMID- 30102453
TI  - Anomalous Dynamics of Magnetic Anisotropic Colloids Studied by XPCS.
AB  - The influence of an applied magnetic field on the collective dynamics of novel
      anisotropic colloidal particles whose shape resembles peanuts is reported. Being
      made up of hematite cores and silica shells, these micrometer-sized particles
      align in a direction perpendicular to the applied external magnetic field, and
      assemble into chains along the field direction. The anisotropic dynamics of these
      particles is investigated using multispeckle ultrasmall-angle X-ray photon
      correlation spectroscopy (USA-XPCS). The results indicate that along the
      direction of the magnetic field, the particle dynamics strongly depends on the
      length scale probed. Here, the relaxation of the intermediate scattering function
      follows a compressed exponential behavior at large distances, while it appears
      diffusive at distances comparable or smaller than the particle size.
      Perpendicular to the applied field (and along the direction of gravity), the
      experimental data can be quantitatively reproduced by a combination of an
      advective term originating from sedimentation and a purely diffusive one that
      describes the thermal diffusion of the assembled chains and individual particles.

PMID- 30102454
TI  - Experimental and Theoretical Determination of the pH inside the Confinement of a
      Virus-Like Particle.
AB  - In biology, a variety of highly ordered nanometer-size protein cages is found.
      Such structures find increasing application in, for example, vaccination, drug
      delivery, and catalysis. Understanding the physiochemical properties,
      particularly inside the confinement of a protein cage, helps to predict the
      behavior and properties of new materials based on such particles. Here, the
      relation between the bulk solution pH and the local pH inside a model protein
      cage, based on virus-like particles (VLPs) built from the coat proteins of the
      cowpea chlorotic mottle virus, is investigated. The pH is a crucial parameter in
      a variety of processes and is potentially significantly influenced by the high
      concentration of charges residing on the interior of the VLPs. The data show a
      systematic more acidic pH of 0.5 unit inside the VLP compared to that of the bulk
      solution for pH values above pH 6, which is explained using a theoretical model
      based on a Donnan equilibrium. The model agrees with the experimental data over
      almost two orders of magnitude, while below pH 6 the experimental data point to a
      buffering capacity of the VLP. These results are a first step in a better
      understanding of the physiochemical conditions inside a protein cage.

PMID- 30102455
TI  - The effect of social deprivation on transplant outcomes using fixed deprivation
      indexes is unlikely to be modified by social mobility.

PMID- 30102457
TI  - Living kidney donor risk of ESRD.

PMID- 30102456
TI  - Structure, Activity, and Faradaic Efficiency of Nitrogen-Doped Porous Carbon
      Catalysts for Direct Electrochemical Hydrogen Peroxide Production.
AB  - Carbon materials doped with nitrogen are active catalysts for the electrochemical
      two-electron oxygen reduction reaction (ORR) to hydrogen peroxide. Insights into
      the individual role of the various chemical nitrogen functionalities in the H2 O2
      production, however, have remained scarce. Here, we explore a catalytically very
      active family of nitrogen-doped porous carbon materials, prepared by direct
      pyrolysis of ordered mesoporous carbon (CMK-3) with polyethylenimine (PEI).
      Voltammetric rotating ring-disk analysis in combination with chronoamperometric
      bulk electrolysis measurements in electrolysis cells demonstrate a pronounced
      effect of the applied potentials, current densities, and electrolyte pH on the H2
      O2 selectivity and absolute production rates. H2 O2 selectivity up to 95.3 % was
      achieved in acidic environment, whereas the largest H2 O2 production rate of
      570.1 mmol g-1 catalyst  h-1 was observed in neutral solution. X-ray
      photoemission spectroscopy (XPS) analysis suggests a key mechanistic role of
      pyridinic-N in the catalytic process in acid, whereas graphitic-N groups appear
      to be catalytically active moieties in neutral and alkaline conditions. Our
      results contribute to the understanding and aid the rational design of efficient
      carbon-based H2 O2 production catalysts.

PMID- 30102458
TI  - Design Principles and Multifunctionality in Cell Encapsulation Systems for Tissue
      Regeneration.
AB  - Cell encapsulation systems are being increasingly applied as multifunctional
      strategies to regenerate tissues. Lessons afforded with encapsulation systems
      aiming to treat endocrine diseases seem to be highly valuable for the tissue
      engineering and regenerative medicine (TERM) systems of today, in which tissue
      regeneration and biomaterial integration are key components. Innumerous
      multifunctional systems for cell compartmentalization are being proposed to meet
      the specific needs required in the TERM field. Herein is reviewed the variable
      geometries proposed to produce cell encapsulation strategies toward tissue
      regeneration, including spherical and fiber-shaped systems, and other complex
      shapes and arrangements that better mimic the highly hierarchical organization of
      native tissues. The application of such principles in the TERM field brings new
      possibilities for the development of highly complex systems, which holds
      tremendous promise for tissue regeneration. The complex systems aim to recreate
      adequate environmental signals found in native tissue (in particular during the
      regenerative process) to control the cellular outcome, and conferring
      multifunctional properties, namely the incorporation of bioactive molecules and
      the ability to create smart and adaptative systems in response to different
      stimuli. The new multifunctional properties of such systems that are being
      employed to fulfill the requirements of the TERM field are also discussed.

PMID- 30102459
TI  - Tunable Interfacial Properties in Silk Ionomer Microcapsules with Tailored
      Multilayer Interactions.
AB  - Microencapsulation techniques represent a critical step in realizing highly
      controlled transport of functional materials in multiphase systems. The first
      demonstration of microcapsules prepared from minimally grafted silk ionomers
      (silk fibroin modified with cationic/anionic charge groups) are presented here.
      These tailored biomacromolecules have shown significantly increased
      biocompatibility over traditional polyelectrolytes and heavily grafted silk
      ionomers, but the low grafting density had previously limited attempts to
      fabricate stable microcapsules. In addition, the first microcapsules from
      polyethylene-glycol-grafted silk ionomers are fabricated and the corresponding
      impact on microcapsule behavior is demonstrated. The materials are shown to
      exhibit pH-responsive properties, with the microcapsules demonstrating an approx.
      tenfold decrease in stiffness and an approx. threefold change in diffusion
      coefficient when moving from acidic to basic buffer. Finally, the effect of
      assembly conditions of the microcapsules are shown to play a large role in
      determining final properties, with microcapsules prepared in acidic buffers
      showing lower roughness, stiffness, and an inversion in transport behavior (i.e.,
      permeability decreases at higher pH).

PMID- 30102460
TI  - Preparation of Pyrimidine Alkenyl Acyclic Nucleoside Phosphonoamidates.
AB  - This synthetic protocol describes two strategies for the preparation of
      pyrimidine alkenyl acyclic nucleoside phosphonoamidates (ANPs), including linear
      and trisubstituted alkenyl derivatives. For the first procedure, a bis
      trimethylsilyl ester of the parent alkenyl ANPs is the key intermediate that
      reacts with the desired amino acid ester and aryl alcohol. For the second
      procedure, an allyl phosphonoamidate bearing the ProTide promoieties is the key
      synthon employed as olefin partner for a cross-metathesis reaction with an
      alkylated nucleobase. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30102461
TI  - Can we mitigate the effects of simultaneous liver-kidney transplantation through
      increased utilization of HCV-positive donors?

PMID- 30102462
TI  - Triggered Cell-Cell Fusion Assay for Cytoplasmic and Organelle Intermixing
      Studies.
AB  - Different multicellular organisms undergo cell-cell fusion to form functional
      syncytia that support specialized functions necessary for proper development and
      survival. For years, monitoring the structural consequences of this process using
      live-cell imaging has been challenging due to the unpredictable timing of cell
      fusion events in tissue systems. Here we present a triggered vesicular stomatitis
      virus G-protein (VSV-G)-mediated cell-cell fusion assay that can be used to
      synchronize fusion between cells. This allows the study of cellular changes that
      occur during cell fusion. The process is induced using a fast wash of low pH
      isotonic buffer, promoting the fusion of plasma membranes of two or more adjacent
      cells within seconds. This approach is suitable for studying mixing of small
      cytoplasmic molecules between fusing cells as well as changes in organelle
      distribution and dynamics. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30102463
TI  - Antiviral therapy for the treatment of HHV-6-associated syndromes after
      transplant.

PMID- 30102464
TI  - Sequence Similarity Searching.
AB  - Sequence similarity searching has become an important part of the daily routine
      of molecular biologists, bioinformaticians and biophysicists. With the rapidly
      growing sequence databanks, this computational approach is commonly applied to
      determine functions and structures of unannotated sequences, to investigate
      relationships between sequences, and to construct phylogenetic trees. We
      introduce arguably the most popular BLAST-based family of the sequence similarity
      search tools. We explain basic concepts related to the sequence alignment and
      demonstrate how to search the current databanks using Web site versions of
      BLASTP, PSI-BLAST and BLASTN. We also describe the standalone BLAST+ tool.
      Moreover, this unit discusses the inputs, parameter settings and outputs of these
      tools. Lastly, we cover recent advances in the sequence similarity searching,
      focusing on the fast MMseqs2 method. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30102465
TI  - Palmitoleic Acid has Stronger Anti-Inflammatory Potential in Human Endothelial
      Cells Compared to Oleic and Palmitic Acids.
AB  - SCOPE: Fatty acids (FAs) may affect endothelial cell (EC) function, influencing
      atherogenesis and inflammatory processes. Palmitoleic acid (POA) has been
      described as an anti-inflammatory FA. However, its effects on ECs are
      underexplored. This study compares the effects of POA with those of palmitic acid
      (PA) and oleic acid (OA) on EC inflammatory responses. METHODS AND RESULTS:
      EAHy926 cells (EC lineage) are exposed to PA, OA, or POA, and stimulated with
      tumor necrosis factor (TNF)-alpha. Associated with the FA's own incorporation, PA
      induces a twofold increase in arachidonic acid, while POA increases the amount of
      cis-vaccenic acid. PA, but not OA, enhances the production of IL-6 and IL-8 in
      response to TNF-alpha. In contrast, POA decreases production of monocyte
      chemotactic protein (MCP)-1, IL-6, and IL-8 compared to PA. TNF-alpha increases
      surface intercellular adhesion molecule-1 expression previously decreased by POA.
      TNF-alpha stimulation increases the expression of NFkappaB, cyclooxygenase (COX)
      2, MCP-1, and IL-6 genes and reduces the expression of peroxisome proliferator
      activated receptor (PPAR)-alpha gene. PA enhances the expression of MCP-1, IL-6,
      and COX-2 genes, while POA downregulates these genes, decreases expression of
      NFkappaB, and upregulates PPAR-alpha gene expression. CONCLUSION: POA has anti
      inflammatory effects on ECs stimulated with TNF-alpha and may counter endothelial
      dysfunction.

PMID- 30102466
TI  - 6-Chloropurine Ribonucleosides from Chloropyrimidines: One-Pot Synthesis.
AB  - A one-pot glycosylation and cyclization procedure is described for the synthesis
      of 6-chloropurine ribonucleosides from chloropyrimidines. From such a procedure
      and modification of the obtained chloropurine ribonucleosides, many drug
      candidates or molecular tools for biological study designed from their similarity
      to naturally occurring nucleosides could be obtained. The synthesis begins by
      preparation of several amidinoaminochloropyrimidines as precursors for the one
      pot procedure. Then, by adding trimethylsilyl trifluoromethanesulfonate (TMSOTf)
      to a mixture of a pyrimidine and 1-O-acetyl-2,3,5-tri-O-benzoyl-beta-D-ribose,
      different 6-chloropurine ribonucleosides are obtained. This methodology allows
      the straightforward introduction of an alkyl substituent at position 8 of purine
      ribonucleosides, which then can be functionalized at positions 2 and 6. (c) 2018
      by John Wiley & Sons, Inc.

PMID- 30102467
TI  - Alkali Lithosilicates: Renaissance of a Reputable Substance Class with Surprising
      Luminescence Properties.
AB  - A hitherto unknown synthetic access to alkali lithosilicates, a substance class
      first described by Hoppe in the 1980s, is reported. With the synthesis and
      characterization of NaK7 [Li3 SiO4 ]8 , a new representative has been discovered,
      expanding the family of known alkali lithosilicates. Astonishingly, NaK7 [Li3
      SiO4 ]8 and the already established alkali lithosilicates Na[Li3 SiO4 ] as well
      as K[Li3 SiO4 ] display unforeseen luminescence properties, when doped with Eu2+
      . Na[Li3 SiO4 ]:Eu2+ exhibits an ultra-narrow blue, K[Li3 SiO4 ]:Eu2+ a
      broadband, and NaK7 [Li3 SiO4 ]8 :Eu2+ a yellow-green double emission upon
      excitation with near-UV to blue light. Consequently, all of the investigated
      substances of this class of compounds are highly interesting phosphors for
      application in phosphor converted LEDs.

PMID- 30102468
TI  - Exploring Factors for the Design of Nanoparticles as Drug Delivery Vectors.
AB  - To achieve optimal results when employing nanoparticles in biomedical fields,
      choosing the right type of nanoparticle and determining the correct procedure for
      drug loading are key factors. Each type of nanoparticle presents a determined set
      of characteristics that are, in some cases, unique. In general, their surface
      charge, geometry or hydrophilic character may be limiting factors, depending on
      what their intended application is. Once synthesized, additional factors, such as
      their interaction with biological systems and liberation mechanisms into the
      target cells, also need to be taken into account. Multiple advantages arise from
      the use of nanoparticles, such as the capability to solubilize hydrophobic
      compounds and an increased bioavailability. Those advantages justify the
      extensive and delicate study that should be undertaken in order to use them as
      drug delivery agents. One of the most important factors for the design of a drug
      delivery system with nanoparticles is achieving a high drug-to-nanoparticle
      ratio. In this Minireview, all of these key factors, both physicochemical and
      biological, are described, and special emphasis is placed on loading methods
      employed to introduce drugs into nanoparticles.

PMID- 30102469
TI  - Enhancing Osteosarcoma Killing and CT Imaging Using Ultrahigh Drug Loading and
      NIR-Responsive Bismuth Sulfide@Mesoporous Silica Nanoparticles.
AB  - Despite its 5-year event-free survival rate increasing to 60-65% due to surgery
      and chemotherapy, osteosarcoma (OS) remains one of the most threatening malignant
      human tumors, especially in young patients. Therefore, a new approach that
      combines early diagnosis with efficient tumor eradication and bioimaging is
      urgently needed. Here, a new type of mesoporous silica-coated bismuth sulfide
      nanoparticles (Bi2 S3 @MSN NPs) is developed. The well distributed mesoporous
      pores and large surface areas hold great promise for drug protection and
      encapsulation (doxorubicin (DOX), 99.85%). Moreover, the high photothermal
      efficiency of Bi2 S3 @MSNs (36.62%) offers great possibility for cancer
      synergistic treatment and highly near-infrared-triggered drug release (even at an
      ultralow power density of 0.3 W cm-2 ). After covalently conjugated to arginine
      glycine-aspartic acid (RGD) peptide [c(RGDyC)], the NPs exhibit a high
      specificity for osteosarcoma and finally accumulate in the tumor cells (tenfold
      more than peritumoral tissues) for computed tomography (CT) imaging and tumor
      ablation. Importantly, the synergistic photothermal therapy-chemotherapy of the
      RGD-Bi2 S3 @MSN/DOX significantly ablates the highly malignant OS. It is further
      proved that the superior combined killing effect is achieved by activating the
      mitochondrial apoptosis pathway. Hence, the smart RGD-Bi2 S3 @MSN/DOX theranostic
      platform is a promising candidate for future applications in CT monitoring and
      synergistic treatment of malignant tumors.

PMID- 30102470
TI  - Synchronized Ratiometric Codelivery of Metformin and Topotecan through Engineered
      Nanocarrier Facilitates In Vivo Synergistic Precision Levels at Tumor Site.
AB  - The combination of metabolic modulators with chemotherapy holds vast promise for
      effective inhibition of tumor progression and invasion. Herein, a ratiometric
      codelivery platform is developed for metformin (MET), a known metabolic modulator
      and topotecan (TPT), a chemotherapeutic drug, by engineering lipid bilayer
      camouflaged mesoporous silica nanoparticles (LB-MSNs). In an attempt to deliver
      and maintain high tumor site concentrations of MET and TPT, a novel ion pairing
      assisted loading procedure is developed using pamoic acid (PA) as an in situ
      trapping agent. PA, a hydrophobic counterion, increases the hydrophobicity of MET
      and TPT and facilitates MSNs with exceptionally high payload capacity (>40 and 32
      wt%, respectively) and controlled release profile. Further, the synergy between
      MET and TPT determined by a modeling approach helps to afford synchronized
      delivery of both the drugs. Coloaded MET and TPT LB-MSNs present synergistic
      cytotoxicity against MDA-MB-231/4T1 cells and effectively promote apoptosis via
      mitochondrial membrane depolarization and cell cycle arrest. Extended
      pharmacokinetic profiles in preclinical models with fourfold to sevenfold longer
      circulation half-life and 7.5-100 times higher tumor site concentrations
      correspond to a significant increase in pharmacodynamic efficacy. Taken together,
      the developed codelivery approach effectively addresses the challenges in the
      chemotherapeutic efficacy of MET and TPT collectively.

PMID- 30102471
TI  - Selective Boryl-Anion Migration in a Vinyl sp2 -sp3 Diborane Induced by Soft
      Borane Lewis Acids.
AB  - An intramolecular 1,2-boryl-anion migration from boron to carbon has been
      achieved by selective activation of the pi system in [(vinyl)B2 Pin2 )]- using
      "soft" BR3 electrophiles (BR3 =BPh3 or 9-aryl-BBN). The soft character is key to
      ensure 1,2-migration proceeds instead of oxygen coordination/B-O activation. The
      BR3 -induced 1,2-boryl-anion migration represents a triple borylation of a vinyl
      Grignard reagent using only B2 Pin2 and BR3 and forms differentially protected
      1,1,2-triborylated alkanes. Notably, by increasing the steric bulk at the beta
      position of the vinyl Grignard reagent used to activate B2 Pin2 , 1,2-boryl-anion
      migration can be suppressed in favor of intermolecular {BPin}- transfer to BPh3 ,
      thus enabling simple access to unsymmetrical sp2 -sp3 diboranes.

PMID- 30102473
TI  - Clinical and molecular evaluation of 16 patients with Rett syndrome.
AB  - Zengin-Akkus P, Taskiran EZ, Kabacam S, Simsek-Kiper PO, Haliloglu G, Boduroglu
      K, Utine GE. Clinical and molecular evaluation of 16 patients with Rett syndrome.
      Turk J Pediatr 2018; 60: 1-9. Rett syndrome is a neurodevelopmental disorder
      caused by mutations in MECP2. The disease is characterized by early neurological
      regression following a normal initial development. The diagnosis is a clinical
      one, based on major and minor diagnostic criteria. This study, in a group of
      patients from a single tertiary center, aimed to evaluate the efficiency of
      clinical diagnosis and to see if there was a diagnostic delay. A second aim was
      to investigate genotype-phenotype correlations, based on Pineda scores. In this
      study, sixteen patients with a median age of 6.5 years (2.5-22 years) were
      included, following molecular confirmation of clinical diagnosis. The median age
      at the onset of symptoms and the median age at clinical diagnosis was 1.5 years
      and 2.5 years, respectively, the difference being statistically significant.
      Considering the Rett syndrome diagnostic criteria, initially regulated in 2002
      and revised in 2010, seven and two patients in our group, respectively, did not
      meet the main criteria. Pineda scores among mutation groups were statistically
      not different. To conclude, the present study revealed presence of a diagnostic
      delay. The challenge may be that the patients do not exhibit full-blown clinical
      picture initially. No genotype-phenotype correlations were detected in clinical
      severity, as measured by Pineda scores. Moreover, the diagnostic criteria revised
      in 2010 are more comprehensive as compared to the 2002 criteria; however, further
      revision may increase diagnostic sensitivity.

PMID- 30102472
TI  - BMP-2 induces human mononuclear cell chemotaxis and adhesion and modulates
      monocyte-to-macrophage differentiation.
AB  - Type 2 diabetes mellitus (T2DM) is a cardiovascular risk factor which leads to
      atherosclerosis, an inflammatory disease characterized by the infiltration of
      mononuclear cells in the vessel. Bone morphogenetic protein (BMP)-2 is a cytokine
      which has been recently shown to be elevated in atherosclerosis and T2DM and to
      contribute to vascular inflammation. However, the role of BMP-2 in the regulation
      of mononuclear cell function remains to be established. Herein, we demonstrate
      that BMP-2 induced human monocyte chemotaxis via phosphoinositide 3 kinase and
      mitogen-activated protein kinases. Inhibition of endogenous BMP-2 signalling, by
      Noggin or a BMP receptor inhibitor, interfered with monocyte migration. Although
      BMP-2 expression was increased in monocytes from T2DM patients, it could still
      stimulate their migration. Furthermore, BMP-2 interfered with their
      differentiation into M2 macrophages. Finally, BMP-2 both induced the adhesion of
      monocytes to fibronectin and endothelial cells (ECs), and promoted the adhesive
      properties of ECs, by increasing expression of adhesion and pro-inflammatory
      molecules. Our data demonstrate that BMP-2 could exert its pro-inflammatory
      effects by inducing monocyte migration and adhesiveness to ECs and by interfering
      with the monocyte differentiation into M2 macrophages. Our findings provide novel
      insights into the mechanisms by which BMP-2 may contribute to the development of
      atherosclerosis.

PMID- 30102474
TI  - The value of nasopharyngeal aspirate, gastric aspirate and bronchoalveolar lavage
      fluid in the diagnosis of childhood tuberculosis.
AB  - Cakir E, Ozdemir A, Daskaya H, Umutoglu T, Yuksel M. The value of nasopharyngeal
      aspirate, gastric aspirate and bronchoalveolar lavage fluid in the diagnosis of
      childhood tuberculosis. Turk J Pediatr 2018; 60: 10-13. Pulmonary tuberculosis
      (TB) is an important cause of morbidity and mortality especially in developing
      countries. A definitive microbiologic confirmation of Mycobacterium tuberculosis
      is important in the diagnosis of childhood TB. We aimed to compare the diagnostic
      value of nasopharyngeal aspirate (NPA), gastric aspirate (GA) and bronchoalveolar
      lavage (BAL) specimens in children with highly suspected pulmonary tuberculosis
      (TB). NPA, GA and BAL samples were obtained from forty patients. The mean age was
      9.2+/-4.7 years. Sixty-eight percent of children had a history of household
      contact and 82% had tuberculin skin test positivity. Acid-fast bacilli (AFB)
      stain was positive in 22.5% (N=9) of BAL, 17.5% (N=7) of GA, and 10% (N=4) of NPA
      samples. Positive Lowenstein-Jensen culture was 27.5% (N=11) in BAL, 22.5% (N=9)
      in GA, and 12.5% (N=5) in NPA samples. Positive AFB stains and growth in TB
      cultures from BAL fluid and GA samples were both higher than NPA samples (p <
      0.006 and p < 0.004, respectively GA). We conclude that NPA specimen fails to
      determine Mycobacterium tuberculosis in children with highly suspected pulmonary
      TB when compared to GA or BAL fluid.

PMID- 30102475
TI  - C1q nephropathy among children with nephrotic syndrome: Ten-year experience from
      a pediatric nephrology unit.
AB  - Abu-Shahin N, Al-Khader A, Qattan D, Akl K. C1q nephropathy among children with
      nephrotic syndrome: Ten-year experience from a pediatric nephrology unit. Turk J
      Pediatr 2018; 60: 14-21. C1q nephropathy (C1qN) is a rare glomerulopathy mostly
      seen in children, and presents with nephrotic syndrome (NS). Diagnosis depends on
      immunoflourescence or immunohistochemical C1q mesangial deposition, excluding
      other immune-mediated diseases. We retrospectively investigated C1qN incidence,
      clinicopathological features, and outcome among pediatric NS in our
      institution.Clinical data, microscopic slides and corresponding tissue blocks of
      pediatric renal biopsies were retrieved. According to diagnostic criteria for
      C1qN, 53 pediatric NS renal biopsies were selected for Anti-C1qA IHC stain
      microscopic examination. Clinicopathological features and follow up data were
      recorded. C1qN incidence was 9.4% among pediatric NS biopsies. Mesangial
      proliferation was the most common histopathological pattern. Steroid dependency
      with frequent relapses was the most frequent outcome, with a second line
      immunosuppressant added, yet without impact on progression. Small sample size
      hinders coherent conclusions; nevertheless, it indicates that C1qN is a rare
      cause of pediatric NS. C1qN may require second line immunosupressants more often
      than non-C1q NS.

PMID- 30102476
TI  - Investigation of the frequency of iron insufficiency among infants in a
      population in which routine iron supplementation is implemented.
AB  - Cullas-Ilarslan NE, Gunay F, Ileri DT, Elhan AH, Ertem M, Arsan S. Investigation
      of the frequency of iron insufficiency among infants in a population in which
      routine iron supplementation is implemented. Turk J Pediatr 2018; 60: 22-31. Iron
      deficiency anemia (IDA) represents the most common cause of anemia worldwide.
      Because of potential irreversible neurodevelopmental impairment, its prevention
      during infancy is essential. We aimed to investigate the frequency of iron
      insufficiency among infants in a population which routine iron supplementation is
      implemented; and to examine related risks. A total of 501 infants, aged 9-15
      months, were screened with complete blood count and serum ferritin. Infants were
      divided into two groups. [Group 1 (iron insufficient), [Group 1a: Iron deficiency
      (ID), Group 1b: IDA (IDA)], Group 2 (Iron sufficient (IS)]. Anemia was recognized
      in 122 (24.3%) infants. Microcytosis was observed in 110 (90.2%) of anemic
      infants. Group 2 accounted for 49.5% (n=248) whereas 152 (30.3%) and 101 (20.2%)
      infants belonged to Groups 1a and 1b, respectively. Multiple logistic regression
      analysis showed that male gender (OR=1.53; 95%CI 1.07 and 2.17), receiving > 500
      ml/day cow's milk (OR=2.77; 95%CI 0.87 and 8.83) and incompliance to iron
      supplementation (OR=2.51; 95%CI 1.75 and 3.60) were distinctive characteristics
      of Group 1 while prevalence of iron insufficiency was higher in infants consuming
      less formula (OR=3.10; 95%CI 2.00 and 4.80). The most frequent reasons for
      incompliance were consideration of supplementation as unnecessary (n=69, 31.1%)
      and neglection (n= 59, 26.6%). Our study demonstrated a high frequency of iron
      insufficiency among infants in a setting utilizing national iron supplementation
      and 'incompliance' to iron as the most evident risk factor for iron
      insufficiency. Effective counseling of families by health care providers
      concerning importance of compliance to iron prophylaxis is essential for
      prevention of iron insufficiency. We also suggest screening of infants for ID as
      well as IDA in settings with high frequency of iron insufficiency.

PMID- 30102477
TI  - Psychiatric morbidity and quality of life in children and adolescents with cystic
      fibrosis.
AB  - Senses-Dinc G, Ozcelik U, Cak T, Dogru-Ersoz D, Cop E, Yalcin E, Cengel-Kultur E,
      Pekcan S, Kiper N, Unal F. Psychiatric morbidity and quality of life in children
      and adolescents with cystic fibrosis. Turk J Pediatr 2018; 60: 32-40. The aim of
      this study was to investigate psychiatric disorders, depression and anxiety
      levels, and quality of life in children and adolescents with cystic fibrosis
      (CF), and to compare them with those of children with non-cystic fibrosis (non
      CF) bronchiectasis and healthy controls. A total of 103 children and adolescents
      aged 7-16 years (35 CF, 28 non-CF bronchiectasis, 40 healthy) were evaluated
      using The Schedule for Affective Disorders and Schizophrenia for School Aged
      Children (K-SADS), The Child Depression Inventory (CDI), The State-Trait Anxiety
      Inventories for Children (STAI-C) and the Pediatric Quality of Life Inventory
      (PedsQL)-C. The three groups were not statistically different with respect to
      age, sex, and familial sociodemographic variables. 80% of the children and
      adolescents in the CF group were diagnosed with a psychiatric disorder, which was
      significantly more compared to those of the two other groups. The CF group had
      significantly greater rates of depressive and oppositional defiant disorder and
      the non-bronchiectasis group had a significantly greater rate of anxiety disorder
      than the control group. The depression and anxiety symptom levels were
      significantly greater and the quality of life levels significantly lower in both
      the CF and non-CF bronchiectasis groups than the healthy controls. In the CF
      group, the presence of any associated psychiatric disorder led to significantly
      lower total and psychosocial quality of life scores. In conclusion, CF is
      associated with poorer QOL in childhood. In order to improve quality of life in
      CF, the psychiatric conditions of children and adolescents should also be
      evaluated and their follow-up and treatment should involve a multidisciplinary
      team approach.

PMID- 30102478
TI  - Allergen variability and house dust mite sensitivity in pre-school children with
      allergic complaints.
AB  - Yazici S, Gunes S, Kurtulus-Cokboz M, Kemer O, Baranli G, Asik-Akman S, Can D.
      Allergen variability and house dust mite sensitivity in pre-school children with
      allergic complaints. Turk J Pediatr 2018; 60: 41-49. The increase in the
      prevalence of allergic diseases in pre-school children who are often at home may
      be due to an increase in house dust mite sensitivity, which is rarely expected in
      this age group. In our study, it was aimed to investigate allergen sensitivities,
      especially house dust mite sensitivity in pre-school children with allergic
      disease complaints by skin prick test (SPT). Two hundred and twenty children
      admitted to the Pediatric Allergy and Asthma Clinic of Balikesir University
      between October 2015 and October 2016 diagnosed with asthma, allergic rhinitis,
      food allergy, atopic dermatitis or urticaria were involved in the retrospective
      cross-sectional study. Allergen groups used in SPT were Dermatophagoides farina
      (Derf), Dermatophagoides pteronyssinus (Der p), Alternaria alternata, cat
      epithelium, pollen mixture and food mixture. Average age of the 220 patients was
      2.98 years (2.75-3.21). SPT was positive in 55.9% of patients. Sixteen percent
      were monosensitized and 73.8% were polysensitized. Seventy two children (32.7%)
      were sensitive to Der f and 67 (30.4%) were sensitive to Der p. There was no
      difference between SPT positivity and gender (p > 0.05). Ninty-five children were
      diagnosed with asthma, 38 with asthma and allergic rhinitis, 63 with food allergy
      and 24 with urticaria and/or atopic dermatitis. SPT positivity was significantly
      higher in the asthma and allergic rhinitis group than other groups. As the age
      increased, significant increases in the sensitivities of Der f (p < 0.01), Der p
      (P < 0.01) and A. alternata (p < 0.05) and a significant decrease for food panel
      sensitivity (p < 0.01) were detected. Even though skin and food allergies were
      included in our study, house dust mite sensitivity was found much higher than
      other studies reporting ranges between 3.5-23% in children of the same age group
      with mainly respiratory complaints. It is concluded that the probable reasons for
      this increase, especially geographical features, should be investigated in
      different areas and in larger number of studies.

PMID- 30102479
TI  - Knowledge levels related to allergen specific immunotherapy and perspectives of
      parents whose children were diagnosed with asthma and/or allergic rhinitis in
      Turkey.
AB  - Isik S, Caglayan-Sozmen S, Asilsoy S, Kilicarslan SK, Anal O, Karaman O, Uzuner
      N. Knowledge levels related to allergen specific immunotherapy and perspectives
      of parents whose children were diagnosed with asthma and/or allergic rhinitis in
      Turkey. Turk J Pediatr 2018; 60: 50-55. In the present study, we aimed to
      evaluate the knowledge levels and perspectives about allergen specific
      immunotherapy (ASI) of parents whose children were diagnosed with asthma and/or
      allergic rhinitis with positive skin prick test. The study was conducted between
      September 2014 and January 2015. Surveys that were filled by 198 parents were
      analyzed. One hundred-ninety-eight parents were included in the study; 42.9% of
      the parents had knowledge about ASI. Parents obtained information about the ASI
      from respectively pediatric allergy specialists (25.5%), relatives and friends
      (17.8%), media (12.9%), and pediatrician (8.2%). There is a strong association
      between educational level of the mother, atopy background of the family, the
      monthly per capita income, and having knowledge about the ASI. Multivariate
      regression analysis revealed that individuals with a monthly income higher than
      2,000 TL were more likely to be aware of the ASI application (OR: 4.35, 95% CI:
      1.13-16.71; p < 0.05). Eighty-nine percent of the parents stated that they would
      prefer the sublingual ASI instead of subcutaneous ASI because it is easy to use
      and its severe side effects risk is low. The awareness of the ASI is at high
      rates in our patient population.

PMID- 30102480
TI  - Outbreak of varicella in preschool children despite one-dose vaccination.
AB  - Kurugol Z, Gokce S. Outbreak of varicella in preschool children despite one-dose
      vaccination. Turk J Pediatr 2018; 60: 56-62. In Turkey, a single-dose varicella
      vaccine was introduced into the National Immunization Program in 2013. Before
      this implementation, varicella vaccine had been available in the private sector
      since 2000. However, varicella outbreaks continued to occur in preschools and
      elementary schools. We investigated a varicella outbreak to estimate the
      effectiveness of 1-dose varicella vaccine and to evaluate potential risk factors
      for breakthrough disease. This study was carried out during a varicella outbreak
      in 3 preschools in Izmir, Turkey, in April 2016. Using questionnaires, data
      including children's medical and vaccination histories were collected from their
      parents. Attack rates in vaccinated and unvaccinated children were calculated and
      the analyses of vaccine effectiveness and of risk factors for breakthrough
      disease were conducted. A total of 124 children were enrolled in the study. Of
      the 124 children, 77 (62%) had received 1-dose varicella vaccine before the
      outbreak. Varicella developed in 34 of 124 children during the outbreak, and 18
      of them (53%) had breakthrough varicella. The attack rate was 23.4% among
      vaccinated children and 34% among unvaccinated children. The effectiveness of
      single-dose varicella vaccine was 33.6% against varicella disease of any severity
      and 82.5% against moderate or severe varicella. Children vaccinated 5 or more
      years before the outbreak had 3.5 times the risk of disease than those who had
      been vaccinated more recently (OR 3.5 [95% CI, 1.08-11.5]); p= 0.046). Age at
      vaccination ( < 15 months vs.>=15 months) and the brands of varicella vaccine
      were not associated with the increased risk of breakthrough varicella. Our study
      suggests that one-dose of varicella vaccine is not sufficient to prevent school
      outbreaks. A 2-dose varicella vaccination program may help to prevent varicella
      outbreaks and achieve effective control of the disease.

PMID- 30102481
TI  - Assessment of central venous catheterization and complications in a tertiary
      pediatric intensive care unit.
AB  - Tolunay I, Yildizdas RD, Elci H, Alabaz D. Assessment of central venous
      catheterization and complications in a tertiary pediatric intensive care unit.
      Turk J Pediatr 2018; 60: 63-69. In catheter-using units as pediatric intensive
      care, it is important to know the complications that may occur during the
      insertion and use of central venous catheterization (CVC), and to take
      appropriate measures in order to reduce the mortality and morbidity of critical
      patients. The aim of this study was to evaluate CVC and catheter related
      complications in our tertiary pediatric intensive care unit. For this prospective
      study, 155 central venous catheters and/or hemodialysis catheters used with 106
      patients, between August 2014 and August 2015 were evaluated. Demographic
      information about patients, catheter insertion procedure and catheter related
      complications were recorded. Sixty-two (58.5%) male and forty-four (41.5%) female
      patients were evaluated in this study. The median age was 67.5 months (1-212).
      The mean dwell time of catheters was 10.54+/-8 days. Twenty-two (14.2%) catheters
      were removed from patients because of catheter related complications. The mean
      dwell time of complicated catheters was 10.6+/-8.5 days and there was no
      statistically significant difference between complicated and non-complicated
      catheters. Catheter related blood stream infections was diagnosed in 5.1% (8/155)
      patients and these catheters were removed from patients. Including these
      patients, positive blood culture was found to be at 14.2% (22/155). The mean
      dwell time of catheters with positive blood culture was 14.25+/-7.3 days. The
      mean dwell time of catheters with positive blood culture was statistically
      significantly longer than catheters with negative blood culture. In the 3
      patients who developed catheter thrombosis, 2 patients were followed up because
      of infection/sepsis and 1 patient had a neurological disease. Catheter thrombosis
      developed in 1 femoral vein and 2 internal jugular veins. The development of
      central venous catheter complications depends on many different factors and it is
      possible to reduce the complications with precautions taken during replacement
      and daily use.

PMID- 30102482
TI  - Restless leg syndrome in children with celiac disease.
AB  - Isikay S, Isikay N, Per H, Carman KB, Kocamaz H. Restless leg syndrome in
      children with celiac disease. Turk J Pediatr 2018; 60: 70-75. Celiac disease (CD)
      is an immune-mediated enteropathy triggered by ingestion of dietary gluten in
      genetically predisposed individuals. The aim of the study was to determine the
      prevalence of restless leg syndrome (RLS) in children with CD and to investigate
      the associated factors for RLS. Totally 494 children with the ages ranging
      between 11-18 years were included. Among those, 226 were under follow-up with CD
      and constituted the study group while other 268 children did not have any
      symptoms or signs associated with CD and established the control group. The
      demographic data, educational status and routine laboratory data of children
      including complete blood count, ferritin, vitamin B12, foliate and 25 (OH)
      vitamin D levels were recorded. The RLS prevalence and associated symptoms of
      children were defined with a questionnaire. There was no statistically
      significant difference between the 2 groups regarding the age and gender.
      Moreover, RLS prevalence was also similar in both groups (3.5% vs 3.0% in CD and
      control groups, respectively, p=0.98). However, interestingly, in CD group, the
      mean age of the patients at the onset of RLS symptoms was statistically
      significantly younger (p=0.02) and the disease was more severe (p=0.026) than the
      control group. In correlation analysis in CD group, the RLS severity
      significantly negatively correlated with serum ferritin, folic acid or 25 (OH)
      vitamin D levels in Celiac disease group. In this study we did not determine an
      increased prevalence of RLS in children with CD. However, in CD group, the age at
      the onset of RLS symptoms was significantly younger and the disease was more
      severe in CD group compared with the control cases.

PMID- 30102484
TI  - Hemolytic uremic syndrome and IgA nephropathy in a child: Coincidence or not?
AB  - Surmeli-Doven S, Delibas A, Gurses I, Kayacan UR, Coskun-Yilmaz B, Esen K,
      Korkmaz E, Ozaltin F. Hemolytic uremic syndrome and IgA nephropathy in a child:
      Coincidence or not? Turk J Pediatr 2018; 60: 81-85. A previously healthy 18-month
      old boy, presenting with diarrhea, anemia, thrombocytopenia and acute renal
      failure was admitted to our hospital. Hemolytic uremic syndrome (HUS) was
      diagnosed with his clinical and laboratory findings. His stool was negative for
      Shiga toxin producing E. coli (STEC). During follow-up he developed respiratory
      distress, hypertrophic cardiomyopathy and seizure. His genetic tests for atypical
      HUS (aHUS) were negative. His clinical and histological findings indicated
      hemolytic uremic syndrome and immunglobulin A nephropathy (IgAN). The patient
      responded to steroid treatment and plasma exchange therapy with peritoneal
      dialysis. We discuss the probable connection between HUS and IgAN.

PMID- 30102483
TI  - A novel homozygous W99G mutation in CLDN-16 gene causing familial hypomagnesemic
      hypercalciuric nephrocalcinosis in Turkish siblings.
AB  - Alparslan C, Oncel EP, Akbay S, Alaygut D, Mutlubas F, Tatli M, Konrad M,
      Yavascan O, Kasap-Demir B. A novel homozygous W99G mutation in CLDN-16 gene
      causing familial hypomagnesemic hypercalciuric nephrocalcinosis in Turkish
      siblings. Turk J Pediatr 2018; 60: 76-80. Familial hypomagnesemic hypercalciuric
      nephrocalcinosis (FHHNC) (OMIM: 248250) is characterized by hypomagnesemia,
      hypercalciuria and nephrocalcinosis. FHHNC inevitably progresses to end-stage
      renal disease in decades. Mutations in CLDN-16 and CLDN-19 genes are associated
      with disrupted magnesium handling in the thick ascending limp of Henle's loop.
      Patients with mutations in these genes share similar clinical features, and those
      with CLDN-19 gene mutations have ocular findings in addition. A 2-month-old boy,
      was admitted to our clinic with the complaints of upper respiratory tract
      infection. He was the first-born child of consanguineous parents. Laboratory
      findings revealed hypocalcemia and hypomagnesemia. Bilateral medullary
      nephrocalcinosis was detected on abdominal ultrasound. His ophthalmologic
      examination was unremarkable. With hypomagnesemia, hypercalciuria and
      nephrocalcinosis, the patient was considered to have FHHNC. Oral magnessium
      supplementation was initiated. Four years of follow-up has been completed
      uneventfully. When 6-days-old the brother of the case above was admitted with
      seizure. The patient was resistant to calcium and anticonvulsant drugs and the
      seizure activity could only be controlled after magnesium infusion. Biochemistry
      profile revealed hypocalcemia and hypomagnesemia. Urinary calcium extraction was
      11 mg/kg/day. Medullary nephrocalcinosis was reported on renal ultrasound. His
      eye examination, echocardiography, transfontanel ultrasound and
      electroencephalography were normal. Due to the triad of hypomagnesemia,
      hypercalciuria and nephrocalcinosis, and the medical history of his elder
      brother, he was diagnosed with FHHNC. After correction of the electrolyte
      abnormalities, he was discharged from hospital and is currently being followed-up
      without any problem. In this manuscript, we shared our experience about a novel
      homozygous mutation (W99C) in CLDN-16 gene causing FHHNC in a couple of Turkish
      siblings.

PMID- 30102485
TI  - A rare reason in a child with feeding intolerance: Intravaginal struvite stone.
AB  - Tokgoz Y, Erdem AO, Ozbey BC, Terlemez S. A rare reason in a child with feeding
      intolerance: Intravaginal struvite stone. Turk J Pediatr 2018; 60: 86-88. Vaginal
      stones are rarely seen in childhood; they are categorized as primary and
      secondary whether they are a foreign object focus (nidus) or not. Urethrovaginal
      fistula is the most common etiological cause; other etiologies are considerably
      rarely reported. Primary vaginal stones are formed as a result of urinary salt
      accumulate. A 14-year-old girl, suffering from an unidentified neurodegenerative
      disease, was admitted with complaints of cough, poor feeding and vomiting.
      Abdominal X-ray showed a large calcific mass; further evaluation revealed a
      vaginal struvite stone, and it was removed surgically. No anatomical reason was
      determined for the formation of stone and it was accepted as primary vaginal
      stone.

PMID- 30102486
TI  - Anauxetic dysplasia: A rare clinical entity.
AB  - Akgun-Dogan O, Simsek-Kiper PO, Utine GE, Boduroglu K. Anauxetic dysplasia: A
      rare clinical entity. Turk J Pediatr 2018; 60: 89-93. Cartilage hair hypoplasia
      and anauxetic dysplasia spectrum constitute a group of autosomal recessive
      disorders characterized by variable extent of metaphyseal to
      spondylometaepiphyseal involvement and various additional clinical features.
      Within this group, anauxetic dysplasia represents the severe end of the skeletal
      spectrum. However, extraskeletal features including immunodeficiency,
      hematological abnormalities, and hair hypoplasia are absent, despite the severe
      skeletal involvement. This disorder is caused by mutations in the gene encoding
      ribonuclease mitochondrial RNA-processing complex. We herein report on a patient
      with anauxetic dysplasia, who presented with severe roto-scoliosis and skeletal
      findings requiring surgical intervention, and in whom a homozygous RMRP mutation
      was detected.

PMID- 30102487
TI  - Clinical findings in cases with 9q deletion encompassing the 9q21.11q21.32
      region.
AB  - Tug E, Ergun MA, Percin EF. Clinical findings in cases with 9q deletion
      encompassing the 9q21.11q21.32 region. Turk J Pediatr 2018; 60: 94-98. We report
      on a case with developmental delay and dysmorphic craniofacial features, and a
      novel~15.2 Mb interstitial deletion within 9q21.11q21.32 confirmed with array
      comparative genomic hybridization (aCGH). A twenty-two month old boy with
      inability to walk without support, absent speech, and attention deficit and
      hyperactivity disorder was seen in our clinic. His craniofacial examination
      revealed relative macrocephaly, facial asymmetry, frontal bossing, sparse medial
      eyebrows, hypertelorism, broad base to nose, smooth philtrum, large mouth,
      operated cleft lip and wide spaced teeth. The high resolution binding (HRB)
      chromosome analysis revealed an interstitial deletion 46,XY,del(9)(q21) confirmed
      by aCGH revealing; 46,XY,der(9)(pter->q21.11::q21.32
      >qter).arr9q21.11q21.32(71,069,763-86,333,272)X1dn. Genotype-phenotype
      correlations of sixteen cases with 9q21 deletion having different breakpoints and
      variable length revealed common characteristic features including severe
      developmental delay, epilepsy, neuro-behavioural disorders and facial dysmorphism
      including hypertelorism, smooth philtrum and thin upper lip. The smallest
      overlapping deleted region in all defined cases to date including our case
      comprised four genes. Among these deleted genes as in our case, especially RORB
      is considered to be a strong candidate for neurological phenotype.

PMID- 30102488
TI  - Acute peripheral facial paralysis following varicella infection: An uncommon
      complication.
AB  - Hanalioglu D, Ozsurekci Y, Buyukcam A, Gultekingil-Keser A, Teksam O, Ceyhan M.
      Acute peripheral facial paralysis following varicella infection: An uncommon
      complication. Turk J Pediatr 2018; 60: 99-101. Chickenpox is caused by varicella
      zoster virus (VZV/HHV-3), which is one of the eight human herpes viruses.
      Although chickenpox has a good prognosis, neurologic complications including
      encephalitis, acute cerebellar ataxia, myelitis and meningitis may seldom be
      associated with the disease. Peripheral facial palsy (PFP) is an extremely rare
      complication in patients with chickenpox. Herein, we report a 12-year-old boy
      with chickenpox and unilateral peripheral facial palsy, who was successfully
      treated with short-term steroids and physical rehabilitation.

PMID- 30102489
TI  - Pediatric primary anaplastic ganglioglioma with malignant neuronal component.
AB  - Kaymak-Cihan M, Erdis E, Bozkurt S, Unver-Korgali E. Pediatric primary anaplastic
      ganglioglioma with malignant neuronal component. Turk J Pediatr 2018; 60: 102
      106. Gangliogliomas (GGs) represent approximately 0.4%-1.0% of all brain tumors.
      Anaplastic gangliogliomas (AGGs) form 5-10% of all GGs. They are a mixed neuronal
      glial tumor of central nervous system and composed by two cell lines; neuronal
      (ganglionic) and glial cells. Anaplastic component of AGGs is usually glial
      cells. Malignant neuronal component is a rare condition. Here we report an 8-year
      old male patient who was diagnosed with primary AGG with malignant neuronal
      component and was treated with surgery, adjuvant radiotherapy and chemotherapy.

PMID- 30102490
TI  - Multiple cranial nerve schwannomas and meningiomas as a hallmark sign of
      neurofibromatosis type 2 in a child.
AB  - Halefoglu AM. Multiple cranial nerve schwannomas and meningiomas as a hallmark
      sign of neurofibromatosis type 2 in a child. Turk J Pediatr 2018; 60: 107-110.
      Neurofibromatosis type 2 is a rarely encountered autosomal dominant disorder
      manifesting with typical radiological findings. These patients have a
      predilection for development of benign tumors in the central nervous system.
      Although the presenting symptom is most commonly hearing loss due to acoustic
      schwannomas, symptoms emanating from other cranial tumors are not uncommon.
      Herein, we described a 16-year-old male patient presented with multiple
      meningiomas and cranial nerve schwannomas revealed by magnetic resonance imaging.
      He fulfilled the diagnostic criteria of neurofibromatosis type 2 and underwent
      treatment. We emphasized the role of radiology in the early diagnosis of this
      inherited disorder in order to provide a better prognosis.

PMID- 30102491
TI  - Phenytoin induced dystonia.
AB  - Acar T, Alkan G, Caksen H, Ertekin B, Ergin M, Kocak S, Cander B. Phenytoin
      induced dystonia. Turk J Pediatr 2018; 60: 111-112. The abnormalities of
      dopaminergic activity in the basal ganglia have been emphasized to be effective
      in dystonia. We hereby report a case of a 2.5-year-old male patient who presented
      with tonic-clonic sezures and who developed dystonia after being given phenytoin.
      Biperidene hydrochloride was administered intramuscularly; primidone was added to
      the treatment regimen. After a 7-day-follow-up at the hospital, the patient had
      no dystonia and was discharged.

PMID- 30102492
TI  - Transcatheter retrieval of embolized catheter using venovenous loop in a neonate.
AB  - Varan B, Yakut K, Harman A. Transcatheter retrieval of embolized catheter using
      venovenous loop in a neonate. Turk J Pediatr 2018; 60: 113-115. Umbilical venous
      catheters are reliable in providing adequate medical care for premature babies
      however complications include infections, bleeding, thrombosis, catheter
      occlusion and migration of a piece of catheter to other parts in the body. Here,
      we present a case with migration of a piece of umbilical venous catheter which
      has been trapped between hepatic vein and right upper pulmonary vein causing
      apnea episodes, recurrent respiratory symptoms, need for mechanical ventilation
      and increase of acute phase reactants. The embolized catheter was retrieved
      successfully via percutaneous route.

PMID- 30102493
TI  - Assessment of vaccine effectiveness during measles outbreak in the Federation of
      Bosnia and Herzegovina, 2014-2015.
AB  - OBJECTIVE: Between February 2014 and September 2015 a large measles outbreak
      (5,084 cases) occurred in the Federation of Bosnia and Herzegovina (FB&H). The
      aim of this study is to assess the effectiveness of routine measles vaccination
      in the FB&H. METHODS: We conducted an analysis of the resurgence period
      surveillance data and a retrospective cohort study involving primary school aged
      children in randomly selected schools. RESULTS: Measles cases occurred among all
      age groups, mostly among the unvaccinated. Among fully immunized, 2.1% contracted
      measles. Measles vaccine effectiveness was high. The study indicates that one
      dose reduced the risk for measles by 91.9% (95% CI: 81.4-96.4%), two doses
      reduced the risk by 97.3% (95% CI: 95.5-98.4%). No evidence of waning immunity
      was found. Our survey reveals that a significant number of children had no
      immunization status registered. CONCLUSIONS: The results of this study suggest
      that the resurgence was likely caused by an accumulation of measles-susceptible
      children not being vaccinated. This vaccine effectiveness study does not support
      possible vaccination failure as a contributing factor.

PMID- 30102494
TI  - Hepatitis C testing among adults born between 1945 and 1965 in Turkey: a
      multicentre study.
AB  - OBJECTIVE: Hepatitis C virus (HCV) infection is a major public health problem and
      affects large populations all over the world. Serum anti-HCV level is a valuable
      marker to determine HCV infection. Anti-HCV testing has been recommended for high
      risk population. The Center for Disease Control (CDC) and Prevention in the
      United States proposed a new high-risk population group - adults born between
      1945-1965. Under this perspective, we designed a multicentre retrospective study
      to determine the seropositivity of anti-HCV among adults born between 1945 and
      1965 and adults born after 1965 in Turkey. With the data collected, we aimed to
      determine whether there was a need for anti-HCV testing especially in people born
      between 1945 and 1965. METHODS: We requested data from ten different medical
      centres in ten different provinces. Each medical centre collected the anti-HCV
      test results of adult patients for five-year period between 2009 and 2014 from
      hospital records. RESULTS: A total of 974,449 anti-HCV test results were included
      in this study. When the seropositivity rates in the two groups of adults were
      compared, anti-HCV seropositivity rates were higher in nine medical centres out
      of ten. Anti-HCV seropositivity in adults born between 1945-1965 was
      significantly higher than in adults born after 1965 (p < 0.05). CONCLUSIONS: We
      determined that the anti-HCV seropositivity rate is significantly higher in
      adults born between 1945-1965 compared to the younger adults as indicated in the
      literature. According to data from this study together with the WHO and CDC
      suggestions, we believe that it is appropriate to offer anti-HCV serology testing
      for people over 50 years of age since the anti- HCV seroprevalence in this age
      group is relatively high.

PMID- 30102495
TI  - Mortality rate of ICU patients with the Middle East Respiratory Syndrome -
      Coronavirus infection at King Fahad Hospital, Jeddah, Saudi Arabia.
AB  - OBJECTIVE: The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a novel
      coronavirus circulating in the Arabian Peninsula since September 2012. It leads
      to significant respiratory disease and among patients with co-morbidities is
      associated with high mortality. This research studied the mortality rate of MERS
      CoV among intensive care unit (ICU) patients and the correlation of mortality
      with different co-morbidities. METHODS: This was a retrospective observational
      study conducted at the Intensive Care Unit of the King Fahad Hospital, Jeddah,
      Saudi Arabia. Data was obtained through patient chart review. RESULTS: The total
      sample consisted of 52 laboratory-confirmed MERS-CoV infection patients. 39
      patients died, with a 75% case-fatality rate. Many patients had underlying co
      morbidities, including diabetes mellitus (51.9%), hypertension (46.2%), and
      chronic renal disease (21.2%). CONCLUSIONS: MERS-CoV ICU mortality remains
      markedly high due to a combination of factors; the disease process of MERS-CoV
      leads to multiple organ failure, particularly respiratory and renal failure.

PMID- 30102496
TI  - Assessment of work-related stress by using salivary cortisol level examination
      among early morning shift workers.
AB  - OBJECTIVE: Early morning shifts have a negative effect on the hypothalamic
      pituitary-adrenal axis. The aim of this study was to comprehensively assess the
      extent of occupational stress in early shift workers of the car industry by using
      salivary cortisol as an objective marker during a workday and on a day off.
      METHODS: For this cross-sectional epidemiological type of study, a survey
      included 55 suitable volunteers from the car industry. Five saliva samples were
      collected according to the following schedule: during one work day in the
      morning, during the morning shift from 6 a.m. - 2 p.m., then after the shift was
      completed, 3 hours after work and in the evening before going to sleep. Control
      samples were taken from the same participants on a day off. Radioimmunoanalysis
      was used as the main analytical method, and the effect of factors and between
      factor interactions on the levels of salivary cortisol during the workday were
      assessed using an ANOVA model. RESULTS: The cortisol diurnal rhythm was as
      expected, with the highest values in the morning and declining to the lowest
      values in the evening hours. Concentrations of salivary cortisol showed higher
      values during the workday, especially higher concentrations of evening cortisol
      and attenuated cortisol slope. Based on the results, irregular shift work has a
      greater increase in cortisol excretion after waking in the morning and a slower
      progressive recovery of the organism during the workday. In addition, cortisol
      levels were significantly higher in older women than in older men but did not
      differ in younger subjects. CONCLUSIONS: Salivary cortisol levels are a suitable
      objective marker of stress and can be used as a good predictor of occupational
      stress by public health services for the purposes of primary prevention.

PMID- 30102497
TI  - Exposure criteria for evaluating lumbar spine load.
AB  - OBJECTIVE: As a part of regular revision of the List of Occupational Diseases in
      the Czech Republic, efforts have been made to add a new item so that lumbar spine
      disease caused by overload may be recognized as occupational one, with adherence
      to the valid national rules, that is, clinical criteria are met and objective
      assessment confirms working conditions under which, according to recent
      scientific knowledge, such an occupational disease develops. The aim is to
      provide information on the use of a proposed method for working condition
      assessment in a real setting, based on the initial experiences gained from a
      pilot study carried out to validate the method. METHODS: Working conditions were
      assessed in 55 individuals with chronic low back pain (25 males, 30 females; mean
      age 45.6 years; mean length of employment 15.6 years). The assessment was based
      on estimating compressive force on the L4/L5 intervertebral disc when performing
      potentially high-risk work tasks which were entered into four types of checklists
      throughout their work shifts. The compression values were calculated using a
      special module that was developed. RESULTS: In 24 cases comprehensive assessment
      of all tasks performed showed fulfillment of the proposed criteria of working
      conditions needed for recognition of occupational disease. Those included
      healthcare, foundry and forest workers, production operators, cabinetmakers,
      locksmiths, bricklayers, etc. In all the cases, lumbar spine overload was
      associated with work tasks requiring combinations of manual handling of objects
      and trunk rotation or bending. The criteria were not met in 31 subjects. The mean
      length of employment was 15.4 and 15.8 years in patients who met and did not meet
      the proposed criteria, respectively. CONCLUSION: The proposed method proved to be
      applicable in occupational hygiene evaluation in a real setting.

PMID- 30102498
TI  - Impact of socio-demographic characteristics and long-term complications on
      quality of life in patients with diabetes mellitus.
AB  - OBJECTIVE: Diabetes mellitus (DM) has been one of the leading chronic diseases
      worldwide over past decades. The objective of the study was to identify
      predictors associated with health-related quality of life (HRQOL) in diabetic
      patients. METHODS: A cross-sectional questionnaire-based study was conducted at
      the General Hospital of the city of Leskovac, between June and November 2015. The
      Short Form-36 (SF-36) questionnaire, EuroQol-5D (EQ-5D) and EuroQol-VAS (EQ-VAS)
      questionnaires were used. Univariate and multivariate linear regression analyses
      were performed. RESULTS: The total number of patients was 285, 112 men (39.3%)
      and 173 women (60.7%), average age 63.92 +/- 1.07 years. The results of multiple
      linear regression of socio-demographic characteristics in relation to dimensions
      of the quality of life measured by SF-36 and EQ-VAS showed that age, country
      (rural) life, low level of education, retirement, and poor economic status are
      predictors of lower quality of life. Our results showed that employment has a
      significant association with higher Physical Component Score (PCS), Mental
      Component Score (MCS) and EQ-VAS score, which can be explained with higher
      incomes, improved economic status and less possibility for the occurrence of
      depressive mood. Patients without formal education have lower QOL. Univariate
      multiple regression analysis of the presence of micro- and macrovascular
      complications of DM showed that angina pectoris, heart failure, diabetic
      retinopathy, and diabetic nephropathy are the most important factors affecting
      the quality of life in our population. After including the multivariate model,
      all tested complications remained statistically significant. CONCLUSION: Our
      results showed that both socioeconomic and chronic complications are relevant
      factors of HRQOL in type 1 and 2 diabetes mellitus patients. Age, rural
      lifestyle, retirement, lower level of education and low socioeconomic status, as
      well as DM complications (angina pectoris, hearth failure, diabetes nephropathy,
      and diabetes retinopathy) were found to be independent risk factors for the
      component scores of SF-36 and EQ-VAS score. Taking into consideration the results
      obtained, health practitioners should be aware not only of the clinical
      parameters of patients with DM, but also of their educational level and working
      status.

PMID- 30102499
TI  - Prevalence of malnutrition risk among institutionalized elderly from North
      Bohemia is higher than among those in the Capital City of Prague, Czech Republic.
AB  - OBJECTIVE: The aim of the study is to assess the risk of malnutrition among
      institutionalized elderly individuals in North Bohemia and compare it to the risk
      of malnutrition in the capital city of Prague, Czech Republic. In the Czech
      Republic, very few studies have been conducted with the goal of describing and
      evaluating the nutritional status of the institutionalized elderly. METHODS: In
      this study, data was collected from 254 elderly individuals (aged >= 65) residing
      in retirement homes in North Bohemia and then compared with similar data for the
      elderly living in retirement homes in Prague (the data from Prague were
      previously published in 2013). The data included an Mini-Nutritional Assessment
      (MNA) test; anthropometric measurements - Body Mass Index (BMI), waist
      circumference, triceps skinfold thickness; and biochemical parameters - albumin,
      prealbumin, transferrin, urea, and creatinine. RESULTS: Mean BMI values were 27.4
      kg/m2 for females and 26.3 kg/m2 for males. According to the MNA questionnaire,
      10.4% of all tested elderly were malnourished and 50.8% were at risk of
      malnutrition; lager proportion of females were found to be malnourished than
      males. Biochemical indicators supported the MNA results. MNA categories
      correlated positively with independence (r = 0.56; p < 0.001), mental status (r =
      0.54; p < 0.001), mobility (r = 0.46; p < 0.001), calf circumference (r = 0.42; p
      < 0.001), BMI, and the ability to self-feed (both r = 0.37; p < 0.001). The
      percentage of institutionalized elderly with malnutrition living in North Bohemia
      and Prague were about the same; however, the percentage of those at risk of
      malnutrition was higher in North Bohemia (p = 0.006). CONCLUSION: Study results
      confirmed that the institutionalized elderly face issues that lower their
      nutritional status and put them at increased risk; clearly these issues need
      urgent attention.

PMID- 30102500
TI  - Prevalence of risk factors in cardiovascular diseases in selected population of
      the Czech Republic.
AB  - OBJECTIVES: The aim of the study is to describe current prevalence of selected
      risk factors in the Czech general population in a particular region and to
      compare the data with recently published results in the selected population of
      Czech soldiers. The work also deals with the advantages and disadvantages of
      methods determining overweight and obesity. METHODS: Within medical preventive
      examinations the data of 1,051 individuals (482 men, 569 women) were obtained. In
      this group anthropometric parameters such as height, body weight, Body Mass Index
      (BMI), and waist circumference were monitored. From biochemical parameters the
      following values were monitored: glycaemia, uric acid, total cholesterol, LDL
      cholesterol, HDL-cholesterol, and triglycerides. Demographic data such as age,
      gender and achieved education were processed. RESULTS: Average BMI values in men
      were in the overweight range. Monitored average BMI values in women were up to
      standards. Monitored anthropometric parameters significantly increased with the
      age of examined individuals. The highest values of BMI and waist circumference
      were found in the over-50 age group. Selected biochemical parameters also
      increased with the age of examined individuals. Education did not have
      significant influence on the values of selected parameters. A statistically
      significant positive correlation was found between the values of BMI and waist
      circumference. The correlation coefficient in men was r = 0.804, p < 0.001, and
      in women r = 0.858, p < 0.001. CONCLUSION: The work confirmed differences in
      anthropometric parameters between the civilian and military Czech male population
      due to a higher muscle mass percentage in the military population. The work also
      confirmed the significance of further anthropometric methods in diagnostics of
      overweight and obesity. The number of individuals with anthropometric and
      biochemical parameters out of the physiological range is increasing in the over
      50 age category.

PMID- 30102501
TI  - Annual and seasonal trends in mortality rates from cardiovascular diseases in
      Hungary between 1984 and 2013.
AB  - OBJECTIVES: The aim of this study was to investigate annual and seasonal trends
      in mortality rates from cardiovascular diseases in Hungary between 1984 and 2013.
      METHODS: Annual and monthly mortality and population data were obtained from the
      Hungarian Central Statistical Office. The annual mortality data by gender and age
      were available for the following disease classifications of the circulatory
      system: all cardiovascular diseases, all diseases of the heart, hypertension,
      coronary heart disease, and cerebrovascular diseases. Six age groups were defined
      for both sexes. Negative binomial regression was carried out to analyse annual
      trends in age-standardized mortality rates. The Walter-Elwood method was used to
      identify seasonal variation using monthly numbers of deaths. RESULTS: Significant
      decreases in annual mortality rates for all cardiovascular diseases were found,
      but not for hypertension. Age-standardized death rates were higher for men for
      all causes, except for hypertension. The greatest sex difference in the average
      risk of death was observed in the middle-aged groups. The greatest percentage
      decrease in death rates during the study period was seen for both sexes in the
      under 35 age group. The lowest percentage change was observed among people aged
      over 75. Significant seasonality was found in monthly death rates from all
      causes, with a peak in February. CONCLUSIONS: In spite of a decreasing trend in
      the annual mortality rates for cardiovascular diseases, the Hungarian mortality
      rate is still high. Moreover, this study demonstrated a significant winter peak
      in mortality from cardiovascular diseases over a thirty-year period.

PMID- 30102502
TI  - Impact of migration background on health of children and adolescents in Austria.
      Results of the Austrian Health Survey 2014.
AB  - OBJECTIVE: The present study examines the question as to whether the wellbeing of
      children and adolescents in Austria and the use of vaccination are influenced by
      migration background. METHODS: The data was extracted from the Austrian Health
      Survey 2014 (ATHIS 2014). It contains health-related information of 5,277
      children and adolescents aged 0 to 17 years. The analysis was based on logistic
      regression models. RESULTS: To stem from a migration background had no influence
      on the assessment of health or the assessment of complaints. Regarding
      vaccination, the results showed that the children of study participants born in
      non-EU foreign countries had twice the chance of being vaccinated as the children
      of Austria-born parents. No difference existed between the children of Austria
      born parents and the children of parents born in non-EU countries. CONCLUSIONS:
      The analysis suggests that children and adolescents with a migration background
      in Austria are not worse off in terms of their physical wellbeing and vaccination
      status than children without a migration background. Some thought should,
      however, be given to the fact that the notion of migration background refers to a
      heterogenic population. To analyse the risks and chances of children and
      adolescents from different migrant backgrounds, a more differentiated survey of
      their migrant background and social situation and a more differentiated survey of
      health parameters will be required.

PMID- 30102503
TI  - Physical activity of 15-17 years old adolescents in different educational
      settings: a Polish-Czech study.
AB  - OBJECTIVES: The aim of this study was to analyze adolescents' physical activity
      (PA) in two different educational settings, and to estimate the association
      between meeting PA recommendations and specific characteristics of adolescents'
      lifestyle. METHODS: The study was carried out in the Moravia region of the Czech
      Republic and in the Silesia-Opole region of Poland. In total, 1,846 participants
      completed the long International Physical Activity Questionnaire (IPAQ-long)
      using the online Indares system. RESULTS: Results showed that the Polish sample
      was significantly more physically active than the Czech one concerning school PA
      (p < 0.001; eta2 = 0.07). Comparing by gender, significant differences were found
      in vigorous PA (p < 0.001; eta2 = 0.05) and moderate PA (p < 0.001; eta2 = 0.08)
      in both samples. The recommendations for vigorous PA are met by 45.9% of Czech
      boys and 33.4% of girls; and by 64.5% of Polish boys and 51.3% of girls.
      Participation in organized PA was the main correlate to achieve the
      recommendations of vigorous PA in both Czech (p < 0.001; CI = 4.47-9.25) and
      Polish adolescents (p < 0.001; CI = 1.99-5.37). CONCLUSIONS: The Polish
      educational model seems to be more effective for enhancing higher levels of PA
      among youth, as it provides pupils with a wider offer of organized PA. Girls were
      found to be less active than boys at high PA intensities in both countries,
      therefore, more effort must be put on involving them in organized PA.

PMID- 30102504
TI  - Child and parental physical activity: Is there an association with young children
      activity?
AB  - OBJECTIVES: The aim of the study is to examine the physical activity (PA) of
      young children and their parents on weekdays and at the weekend, as well as
      possible associations between them. METHODS: Fifty-eight children (29 boys), aged
      5-8 years (mean age = 6.53 years) and the parent who spent more time with them
      (25 fathers, 33 mothers, mean age 40.67 years) wore Omron HJ-720IT pedometers for
      seven consecutive days. Two ANOVAs for repeated measures were applied to examine
      PA differences between genders and week phases (weekdays vs. weekend days) in
      children and parents. Moreover, one sample t-tests were used to compare
      participants' PA to the recommended PA, while linear regression analyses were
      utilized to examine whether parental PA in each week phase was associated with
      children's PA. RESULTS: Children accumulated more steps on weekdays than at the
      weekend (F1,56 = 18.58, p < 0.001, eta2 = 0.27), while boys presented higher PA
      than girls (F1,56 = 12.42, p = 0.001, eta2 = 0.20), and accomplished the
      recommended daily PA, in contrast to girls. Mothers and fathers presented similar
      PA (p = 0.67, eta2 = 0.004), with more steps on weekdays than at the weekend
      (F1,56 = 9.22, p = 0.004, eta2 = 0.16). However, their PA was significantly lower
      than the recommended. Finally, there were no statistically significant
      associations between parents' and boys' ambulatory activity either on weekdays (p
      = 0.938) or at the weekend (p = 0.095). On the contrary, parents' PA explained
      47% of girls' PA on weekdays (R = 0.68, F1,28 = 22.81, p < 0.001) and 23% at the
      weekend (R = 0.48, F1,28 = 6.40, p = 0.02) Conclusions: Boys appear to be more
      physically active than girls in Greece, whereas mothers and fathers present
      similar ambulatory activity. Moreover, parents' PA is related to that of their
      daughters and not to that of their sons. Taking into account that both girls and
      parents did not meet PA recommendations, family-based interventions are needed
      for both children and parents benefit.

PMID- 30102505
TI  - What do Czech adolescents know about HIV?
AB  - OBJECTIVE: During last years, a significant increase of HIV infection transmitted
      through sexual intercourse among young adults has been reported in the Czech
      Republic. The issue of prevention, where sexual education belongs to an important
      preventive tool, is much more topical than ever before. The level of knowledge
      and attitudes related to HIV/AIDS among adolescents has not been assessed so far.
      The aim of our study was to explore this field in a nationally representative
      sample. METHODS: Information was obtained using an anonymous questionnaire that
      was filled in by 1,627 adolescents 13 to 15 years old selected from a
      representative sample of 25 elementary and grammar schools in the Czech Republic.
      RESULTS: Based on the survey results, good knowledge regarding primary HIV/AIDS
      prevention was noted in the majority of respondents who however tended to
      stigmatize HIV positive people. CONCLUSION: The study has confirmed the
      importance of school as the main source of information (reported by 50.8% of
      respondents). The result of our study can serve as a starting point in assessment
      and comparison of the effect of various educational programmes.

PMID- 30102506
TI  - Timeliness of travel-associated Legionnaires' disease surveillance.
AB  - Letter to the editor, in response to the paper "Legionellosis: a walk-through to
      identification of the source of infection", Cent Eur J Public Health
      2017;25(3):235-239.

PMID- 30102509
TI  - Facile Doping in Two-Dimensional Transition-Metal Dichalcogenides by UV Light.
AB  - Two-dimensional (2D) materials have been emerging as potential candidates for the
      next-generation materials in various technology fields. The performance of the
      devices based on these 2D materials depends on their intrinsic band structures as
      well as the extrinsic (doping) effects such as surrounding chemicals and
      environmental oxygen/moisture, which strongly determines their Fermi energy
      level. Herein, we report the UV treatments on the 2D transition-metal
      dichalcogenides, to controllably dope the samples without damaging the crystal
      structures or quenching the luminescence properties. More surprisingly, both n
      type and p-type doping can be achieved depending on the initial status of the
      sample and the UV treatment conditions. The doping mechanisms were elaborated on
      the atomic scale with transmission electron microscopy and ab initio
      calculations. The facile doping by UV light has potential to be integrated with
      photolithography processes, aiming for the large-scale integrated device/circuits
      design and fabrications.

PMID- 30102510
TI  - Tumor Oxygenation and Hypoxia Inducible Factor-1 Functional Inhibition via a
      Reactive Oxygen Species Responsive Nanoplatform for Enhancing Radiation Therapy
      and Abscopal Effects.
AB  - Hypoxia, and hypoxia inducible factor-1 (HIF-1), can induce tumor resistance to
      radiation therapy. To overcome hypoxia-induced radiation resistance, recent
      studies have described nanosystems to improve tumor oxygenation for immobilizing
      DNA damage and simultaneously initiate oxygen-dependent HIF-1alpha degradation.
      However, HIF-1alpha degradation is incomplete during tumor oxygenation treatment
      alone. Therefore, tumor oxygenation combined with residual HIF-1 functional
      inhibition is crucial to optimizing therapeutic outcomes of radiotherapy. Here, a
      reactive oxygen species (ROS) responsive nanoplatform is reported to successfully
      add up tumor oxygenation and HIF-1 functional inhibition. This ROS responsive
      nanoplatform, based on manganese dioxide (MnO2) nanoparticles, delivers the HIF-1
      inhibitor acriflavine and other hydrophilic cationic drugs to tumor tissues.
      After reacting with overexpressed hydrogen peroxide (H2O2) within tumor tissues,
      Mn2+ and oxygen molecules are released for magnetic resonance imaging and tumor
      oxygenation, respectively. Cooperating with the HIF-1 functional inhibition, the
      expression of tumor invasion-related signaling molecules (VEGF, MMP-9) is
      obviously decreased to reduce the risk of metastasis. Furthermore, the
      nanoplatform could relieve T-cell exhaustion via downregulation of PD-L1, whose
      effects are similar to the checkpoint inhibitor PD-L1 antibody, and subsequently
      activates tumor-specific immune responses against abscopal tumors. These
      therapeutic benefits including increased X-ray-induced damage, downregulated
      resistance, and T-cell exhaustion related proteins expression achieved
      synergistically the optimal inhibition of tumor growth. Overall, this designed
      ROS responsive nanoplatform is of great potential in the sensitization of
      radiation for combating primary and metastatic tumors.

PMID- 30102511
TI  - Interconnected Hollow Cobalt Phosphide Grown on Carbon Nanotubes for Hydrogen
      Evolution Reaction.
AB  - Transition-metal phosphides are deemed as potential alternative to platinum for
      large-scale and sustainable electrocatalytic hydrogen production from water. In
      this study, facile preparation of interconnected hollow cobalt monophosphide
      (CoP) supported on carbon nanotubes is demonstrated and evaluated as a low-cost
      electrocatalyst for hydrogen evolution reaction. Hexamethylenetetramine is used
      as a structure-directing agent to guide the formation of interconnected cobalt
      oxide, which further grows into interconnected hollow CoP. Interconnected and
      hollow microstructural artifacts impart benign attributes, such as enhanced
      specific and electrochemically active surface area, low intrinsic charge transfer
      resistance, high interfacial charge transfer kinetics, and improved mass
      transport, to the electrocatalyst. As a result, the as-prepared electrode
      exhibits remarkable electrocatalytic performance, low onset (18 mV) and
      overpotential (eta10 = 73 mV); small Tafel slope (54.6 mV dec-1); and high
      turnover frequency (0.58 s-1 at eta = 73 mV). In addition, the electrode shows
      excellent electrochemical stability.

PMID- 30102512
TI  - Chemical Structure and Composition of Major Glycans Covalently Linked to
      Therapeutic Monoclonal Antibodies by Middle-Down Nuclear Magnetic Resonance.
AB  - Glycosylation of monoclonal antibodies (mAbs) is a critical quality attribute
      that can impact mAb drug efficacy and safety. The mAb glycans are inherently
      heterogeneous in chemical structure and composition of monosaccharides. The
      established fluorescence or mass-spectrometry (MS) detection methods for
      glycosylation evaluation may require multiple steps of glycan cleavage or
      extensive digestion of the mAb, chemical labeling of the glycans, column
      separation and report the chemical identity of glycans indirectly through
      retention time and molecular weight values. In demonstrating chemical structure
      similarity and comparability among mAb drugs, orthogonal analytical methods for
      measuring glycan chemistry are needed to ensure the quality of drug products.
      Here, a "middle-down" NMR method is developed as a proof-of-concept approach to
      measure the domain-specific glycosylation of marketed mAb drugs without cleavage
      of the glycan moieties. Complete glycan 1H/13C chemical shift assignments were
      obtained at 13C natural abundance from commercial standard glycans that allowed
      unambiguous determination of the chemical structure, glycosidic linkage position,
      and anomeric configuration of each monosaccharide in the major N-glycan scaffolds
      found in mAb molecules. The analysis of glycan anomeric peaks in two-dimensional
      (2D) 1H-13C NMR spectra yielded metrics for clinically important mAb quality
      attributes (i.e., galactosylation (Gal%) and fucosylation (Fuc%)), consistent
      with literature results using a standard glycan-mapping method. Therefore, the
      middle-down NMR method provided a facile orthogonal measurement for mAb
      glycosylation characterization with improved chemical information content on
      glycan structure determination and quantification, compared to standard
      approaches.

PMID- 30102513
TI  - Perfect Complementary in Absorption Spectra with Fullerene, Nonfullerene
      Acceptors and Medium Band Gap Donor for High-Performance Ternary Polymer Solar
      Cells.
AB  - Because of the mismatch between the solar irradiance spectra and the photoactive
      layer absorption spectra, only a part of sunlight can be utilized, which
      fundamentally restricting the power conversion efficiency (PCE) of the polymer
      solar cells (PSCs). Ternary blend PSCs, with an additional third component, have
      become an effective approach to extend the absorption spectra and increase the
      mobility of the charge carriers. Herein, we select the middle band gap PBDTBDD as
      an electron donor and narrow band gap ITIC and wide band gap PC60BM as electron
      acceptors to construct ternary blends for simultaneously enhancing the absorption
      intensity and expanding the absorption band. The optical properties,
      morphologies, and the charge-/energy-transfer behaviors of the ternary blends are
      investigated. By attentively adjusting the ratio of the third component, ITIC,
      the ternary PSCs demonstrate an expanded light-response region and greatly
      enhanced JSC, giving an improved overall PCE of 10.36%, much higher than that of
      the binary counterparts based on PBDTBDD:PC60BM (6.63%) and PBDTBDD:ITIC (9.44%).
      These findings indicate that proper selection of donors and acceptors to
      construct absorption spectra-complementary ternary blend photoactive layers is an
      effective way to achieve high-performance PSCs.

PMID- 30102514
TI  - Microfluidic-Assisted Fabrication of Clay Microgels for Cell-Free Protein
      Synthesis.
AB  - Cell-free protein synthesis (CFPS) is a robust platform for the simple, rapid,
      and cost-effective in vitro production of proteins, as well as an important tool
      for cell-free synthetic biology research. Here, a microfluidic clay microgel
      system is reported, which creates compartmentalized microenvironments for CFPS
      capable of high-yield and repeated protein synthesis, as well as an artificial
      cell-like structure. As an advantageous platform for CFPS, a modular manner to
      prepare clay microgels with rationally designed functions is demonstrated: (i)
      gene/clay microgels enhance protein expression, (ii) gene/clay/magnetic
      nanoparticle microgels enable a repeated protein production system, and (iii)
      gene/clay microgels in microfluidic droplets serve as a cell-like structure.
      Beyond CFPS, considering the compatibility of clay microgels with hydrophilic
      functional materials, our clay microgels will provide a more general platform for
      preparing a variety of functional materials such as encapsulating drugs and
      cells, enabling more biomedical applications.

PMID- 30102515
TI  - Complete Native Stable Isotope Labeling by Amino Acids of Saccharomyces
      cerevisiae for Global Proteomic Analysis.
AB  - Knowledge about the functions of individual proteins on a system-wide level is
      crucial to fully understand molecular mechanisms underlying cellular processes. A
      considerable part of the proteome across all organisms is still poorly
      characterized. Mass spectrometry is an efficient technology for the global study
      of proteins. One of the most prominent methods for accurate proteome-wide
      comparative quantification is stable isotope labeling by amino acids in cell
      culture (SILAC). However, application of SILAC to prototrophic organisms such as
      Saccharomyces cerevisiae, also known as baker's yeast, is compromised since they
      are able to synthesize all amino acids on their own. Here, we describe an
      advanced strategy, termed 2nSILAC, that allows for in vivo labeling of
      prototrophic baker's yeast using heavy arginine and lysine under fermentable and
      respiratory growth conditions, making it a suitable tool for the global study of
      protein functions. This generic 2nSILAC strategy allows for directly using and
      systematically screening yeast mutant strain collections available to the
      scientific community. We exemplarily demonstrate its high potential by analyzing
      the effects of mitochondrial gene deletions in mitochondrial fractions using
      quantitative mass spectrometry revealing the role of Coi1 for the assembly of
      cytochrome c oxidase (respiratory chain complex IV).

PMID- 30102517
TI  - Correction to Metallic Nanoislands on Graphene for Monitoring Swallowing Activity
      in Head and Neck Cancer Patients.

PMID- 30102516
TI  - Microscale Reversed-Phase Liquid Chromatography/Capillary Zone Electrophoresis
      Tandem Mass Spectrometry for Deep and Highly Sensitive Bottom-Up Proteomics:
      Identification of 7500 Proteins with Five Micrograms of an MCF7 Proteome Digest.
AB  - Capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) has been well
      recognized for bottom-up proteomics. It has approached 4000-8000 protein
      identifications (IDs) from a human cell line, mouse brains, or Xenopus embryos
      via coupling with liquid chromatography (LC) prefractionation. However, at least
      500 MUg of complex proteome digests were required for the LC/CZE-MS/MS studies.
      This requirement of a large amount of initial peptide material impedes the
      application of CZE-MS/MS for deep bottom-up proteomics of mass-limited samples.
      In this work, we coupled microscale reversed-phase LC (MURPLC)-based peptide
      prefractionation to dynamic pH-junction-based CZE-MS/MS for deep bottom-up
      proteomics of the MCF7 breast cancer cell proteome starting with only 5 MUg of
      peptides. The dynamic pH-junction-based CZE enabled a 500 nL sample injection
      from as low as a 1.5 MUL peptide sample, using up to 33% of the available peptide
      material for an analysis. Two kinds of MURPLC prefractionation were investigated,
      C18 ZipTip and nanoflow RPLC. C18 ZipTip/CZE-MS/MS identified 4453 proteins from
      5 MUg of the MCF7 proteome digest and showed good qualitative and quantitative
      reproducibility. Nanoflow RPLC/CZE-MS/MS produced over 7500 protein IDs and
      nearly 60 000 peptide IDs from the 5 MUg of MCF7 proteome digest. The nanoflow
      RPLC/CZE-MS/MS platform reduced the required amount of complex proteome digests
      for LC/CZE-MS/MS-based deep bottom-up proteomics by 2 orders of magnitude. Our
      work provides the proteomics community with a powerful tool for deep and highly
      sensitive proteomics.

PMID- 30102518
TI  - Rapid Ion Mobility Separations of Bile Acid Isomers Using Cyclodextrin Adducts
      and Structures for Lossless Ion Manipulations.
AB  - Bile acids (BAs) constitute an important class of steroid metabolites often
      displaying changes associated with disease states and other health conditions.
      Current analyses for these structurally similar compounds are limited by a lack
      of sensitivity and long separation times with often poor isomeric resolution. To
      overcome these challenges and provide rapid analyses for the BA isomers, we
      utilized cyclodextrin adducts in conjunction with novel ion mobility (IM)
      separation capabilities provided by structures for lossless ion manipulations
      (SLIM). Cyclodextrin was found to interact with both the tauro- and glyco
      conjugated BA isomers studied, forming rigid noncovalent host-guest inclusion
      complexes. Without the use of cyclodextrin adducts, the BA isomers were found to
      be nearly identical in their respective mobilities and thus unable to be baseline
      resolved. Each separation of the cyclodextrin-bile acid host-guest inclusion
      complex was performed in less than 1 s, providing a much more rapid alternative
      to current liquid chromatography-based separations. SLIM provided capabilities
      for the accumulation of larger ion populations and IM peak compression that
      resulted in much higher resolution separations and increased signal intensities
      for the BA isomers studied.

PMID- 30102519
TI  - Phosphorescence Lifetime Imaging of Labile Zn2+ in Mitochondria via a
      Phosphorescent Iridium(III) Complex.
AB  - Phosphorescence lifetime Zn2+ imaging possesses the advantage over normal
      fluorescence imaging in offering the more accurate temporal-spatial Zn2+
      information. Herein, we report a new phosphorescent cyclometalated Ir(III)
      complex with a Zn2+-chelator bearing 1,10-phenanthrolin acting as ancillary
      ligand, Zin-IrDPA, which displays the specific Zn2+-induced enhancement of
      phosphorescence and phosphorescence lifetime, and the mitochondria-targeting
      ability. Moreover, its Zn2+-induced phosphorescence lifetime enhancement factor
      is not affected by medium lipophilicity, viscosity, polarity, and especially
      ambient oxygen. The reversible tracking of introduced exogenous labile Zn2+ in
      MCF-7 and HeLa cells via phosphorescence imaging and phosphorescence lifetime
      imaging (PLIM) have been realized with Zin-IrDPA. Moreover, PLIM with Zin-IrDPA
      is able to track the SNOC-stimulated endogenous Zn2+ release in mitochondria.

PMID- 30102520
TI  - Generation and Comparative Kinetic Analysis of New Glycosynthase Mutants from
      Streptococcus pyogenes Endoglycosidases for Antibody Glycoengineering.
AB  - Chemoenzymatic glycan remodeling by endoglycosidase-catalyzed deglycosylation and
      reglycosylation is emerging as an attractive approach for producing homogeneous
      glycoforms of antibodies, and the success of this approach depends on the
      discovery of efficient endoglycosidases and their glycosynthase mutants. We
      report in this paper a systematic site-directed mutagenesis of an endoglycosidase
      from Streptococcus pyogenes (Endo-S) at the critical Asp-233 (D233) site and
      evaluation of the hydrolysis and transglycosylation activities of the resulting
      mutants. We found that in addition to the previously identified D233A and D233Q
      mutants of Endo-S, most of the Asp-233 mutants discovered here were also
      glycosynthases that demonstrated glycosylation activity using glycan oxazoline as
      the donor substrate with diminished hydrolytic activity. The glycosynthase
      activity of the resultant mutants varied significantly depending on the nature of
      the amino acid substituents. Among them, the D233M mutant was identified as the
      most efficient glycosynthase variant with the highest
      transglycosylation/hydrolysis ratio, which is similar to the recently reported
      D184M mutant of Endo-S2, another S. pyogenes endoglycosidase. Kinetic studies of
      the D233M and D233A mutants of Endo-S, as well as glycosynthase mutants D184M and
      D184A of Endo-S2, indicated that the enhanced catalytic efficacy of the Asp-to
      Met mutants of both enzymes was mainly due to an increased turnover number
      (increased kcat) for the glycan oxazoline substrate and the significantly
      enhanced substrate affinity (as judged by the reduced KM value) for the antibody
      acceptor.

PMID- 30102521
TI  - Upscaling Reverse Electrodialysis.
AB  - Salinity gradient energy is a sustainable, renewable, and clean energy source.
      When waters with different salinities are mixed, the change in Gibbs free energy
      can be harvested as energy and only brackish water remains. Reverse
      electrodialysis is one of the technologies that can harvest this sustainable
      energy source. High power densities have been obtained in small lab scale
      systems, but translation to large industrial scale stacks is essential for
      commercialization of the technology. Moreover, power density is an important
      parameter, and efficiency, i.e., the amount of energy harvested compared to the
      amount of energy available in the feed waters, is critical for commercial
      processes. In this work, we systematically investigate the influence of stack
      size and membrane type on power density, thermodynamic efficiency, and energy
      efficiency. Results show that the residence time is an excellent parameter for
      comparing differently sized stacks and translating lab scale experimental results
      to larger pilot stacks. Also, the influence of undesired water permeability and
      co-ion diffusion (as reflected in permselectivity) is clearly visible when
      measuring the thermodynamic efficiency. An averaged thermodynamic efficiency of
      44.9% is measured using Fujifilm Type 10 anion exchange and cation exchange
      membranes that have low water permeability and high permselectivity. This value
      comes close to the thermodynamic maximum of 50%.

PMID- 30102522
TI  - Intermolecular Carboamination of Unactivated Alkenes.
AB  - Herein, we report the first example of group transfer radical addition of O
      vinylhydroxylamine derivatives onto unactivated alkenes. By utilizing O
      vinylhydroxylamine derivatives as both the N- and C-donors, this reaction enables
      intermolecular carboamination of unactivated alkenes in an atom economical
      fashion. As the process is initiated through N-radical addition followed by C
      transfer, linear carboamination products are afforded. This differs from
      canonical radical carbofunctionalization of olefins, which typically favors
      branched product owing to initiation by C-radical addition.

PMID- 30102523
TI  - Entry from the Lipid Bilayer: A Possible Pathway for Inhibition of a Peptide G
      Protein-Coupled Receptor by a Lipophilic Small Molecule.
AB  - The pathways that G protein-coupled receptor (GPCR) ligands follow as they bind
      to or dissociate from their receptors are largely unknown. Protease-activated
      receptor-1 (PAR1) is a GPCR activated by intramolecular binding of a tethered
      agonist peptide that is exposed by thrombin cleavage. By contrast, the PAR1
      antagonist vorapaxar is a lipophilic drug that binds in a pocket almost entirely
      occluded from the extracellular solvent. The binding and dissociation pathway of
      vorapaxar is unknown. Starting with the crystal structure of vorapaxar bound to
      PAR1, we performed temperature-accelerated molecular dynamics simulations of
      ligand dissociation. In the majority of simulations, vorapaxar exited the
      receptor laterally into the lipid bilayer through openings in the transmembrane
      helix (TM) bundle. Prior to full dissociation, vorapaxar paused in metastable
      intermediates stabilized by interactions with the receptor and lipid headgroups.
      Derivatives of vorapaxar with alkyl chains predicted to extend between TM6 and
      TM7 into the lipid bilayer inhibited PAR1 with apparent on rates similar to that
      of the parent compound in cell signaling assays. These data are consistent with
      vorapaxar binding to PAR1 via a pathway that passes between TM6 and TM7 from the
      lipid bilayer, in agreement with the most consistent pathway observed by
      molecular dynamics. While there is some evidence of entry of the ligand into
      rhodopsin and lipid-activated GPCRs from the cell membrane, our study provides
      the first such evidence for a peptide-activated GPCR and suggests that metastable
      intermediates along drug binding and dissociation pathways can be stabilized by
      specific interactions between lipids and the ligand.

PMID- 30102524
TI  - Targeted Maytansinoid Conjugate Improves Therapeutic Index for Metastatic Breast
      Cancer Cells.
AB  - This study was undertaken to target cell surface receptors other than the ones
      typically associated with breast cancer {estrogen receptor (ER), progesterone
      receptor (PR), and human epidermal growth factor receptor 2 (HER2)}. It was also
      launched to use small molecules other than those most widely used for active
      targeting in general ( e.g. folate and carbonic anhydrase IX ligands).
      Specifically, the focus of this study was on unique small molecules that bind the
      TrkC receptor, which is overexpressed in metastatic breast cancer. A conjugate
      (1) of a TrkC-targeting small molecule and the highly cytotoxic warhead, DM4 (a
      maytansinoid), was prepared. Cellular studies featuring TrkC+ and TrkC- human
      breast cells indicated this conjugate might have a better therapeutic effect than
      DM4 alone. It emerged that the conjugate 1 was very efficacious in vivo,
      completely ablating orthotopic 4T1 breast tumor in one case and dramatically
      reducing the tumor size in four other mice. Throughout, no significant weight
      loss or obvious neurotoxic effects were observed in the animals tested.

PMID- 30102525
TI  - Simulating the Advection and Degradation of the Environmental DNA of Common Carp
      along a River.
AB  - The environmental DNA (eDNA) method is a novel technique for precise and
      efficient biological surveillance. Although eDNA has been widely used to monitor
      various freshwater organisms, eDNA dynamics in streams remain poorly understood.
      In this study, we investigated the eDNA dynamics of common carp ( Cyprinus
      carpio) in a forested headwater stream affected by the effluent from a carp farm.
      We evaluated the longitudinal variation in carp eDNA along a river downstream
      from the farm and performed a temporal eDNA decay experiment using digital
      polymerase chain reaction. On the basis of the resulting decay constants, we
      built a model to simulate the advection and degradation of eDNA along the studied
      river. The observed eDNA flux (concentration multiplied by flow rate) decreased
      exponentially with distance downstream from the farm, and eDNA was detected 3 km
      downstream of the farm. Although the water temperatures were similar, the eDNA
      decay constant was lower in autumn than in summer. The simulated eDNA
      concentration was markedly larger (>10 times) than the observed concentration,
      suggesting that eDNA removal is accelerated in the stream environment compared to
      in conventional experimental settings.

PMID- 30102526
TI  - Enantioselective Synthesis of alpha-Amidoboronates Catalyzed by Planar-Chiral NHC
      Cu(I) Complexes.
AB  - The first highly selective catalytic hydroboration of alkyl-substituted aldimines
      to provide medicinally relevant alpha-amidoboronates is disclosed. The Cu(I)
      catalyzed borylation proceeds with excellent facial selectivity when a set of
      planar-chiral N-heterocyclic carbenes (NHCs) were employed as ligands. Density
      functional theory computations suggest that interactions between BPin and the
      planar-chiral catalyst are responsible for the observed stereoselectivity.
      Important pharmacophores, such as the boronate analogue of isoleucine, can be
      prepared using a chromatography-free protocol starting from commercially
      available reagents. The application of these NHC ligands in these Cu(I)-catalyzed
      processes offers a significant contribution to existing strategies for laboratory
      scale preparation of enantioenriched alpha-amidoboronates.

PMID- 30102528
TI  - Rhodium-Catalyzed B-H Bond Insertion Reactions of Unstabilized Diazo Compounds
      Generated in Situ from Tosylhydrazones.
AB  - Although transition-metal-catalyzed B-H bond insertion of carbenes into stable
      borane adducts has emerged as a promising method for organoborane synthesis, all
      the diazo compounds used to date as carbene precursors have had an electron
      withdrawing group to stabilize them. Herein, we report a protocol for rhodium
      catalyzed B-H bond insertion reactions of unstabilized diazo compounds generated
      in situ from tosylhydrazones. In addition, by using chiral dirhodium catalysts,
      we also achieved an asymmetric version of the reaction with good to excellent
      enantioselectivities (up to 98:2 e.r.). This is the first enantioselective
      heteroatom-hydrogen bond insertion reaction to use unstabilized diazo compounds
      as carbene precursors. The protocol exhibited good functional group tolerance and
      could be carried out on a gram scale. It also enabled one-pot transformation of a
      carbonyl group to a boryl group enantioselectively. The B-H bond insertion
      products could be easily transformed into chiral alcohols and other widely used
      organoboron reagents with enantiomeric fidelity.

PMID- 30102527
TI  - Biotin-Modified Polylactic- co-Glycolic Acid Nanoparticles with Improved
      Antiproliferative Activity of 15,16-Dihydrotanshinone I in Human Cervical Cancer
      Cells.
AB  - 15,16-Dihydrotanshinone I (DI), a natural compound isolated from a traditional
      Asian functional food Salvia Miltiorrhiza Bunge, is known for its anticancer
      activity. However, poor solubility of DI limits its desirable anticancer
      application. Herein, polylactic- co-glycolic acid (PLGA) was functionalized with
      polyethylene glycol (PEG) and biotin to form copolymers PEG-PLGA (PPA) and biotin
      PEG-PLGA (BPA). DI was encapsulated in copolymers PPA and BPA to obtain DI-PPA
      NPs (NPs = nanoparticles) and DI-BPA-NPs, respectively. The particle size and its
      distribution, encapsulation efficiency, and in vitro releasing capacity of DI-BPA
      NPs were characterized by biophysical methods. MTT assay was used to evaluate the
      antiproliferative activity of free DI, DI-PPA-NPs, and DI-BPA-NPs in human
      cervical cancer Hela cells. DI-BPA-NPs showed the highest cytotoxicity on Hela
      cells with an IC50 value of 4.55 +/- 0.631 MUM, while it was 8.20 +/- 0.849 and
      6.14 +/- 0.312 MUM for DI and DI-PPA-NPs in 72 h, respectively. The superior
      antiproliferative activity was supported by the fact that DI-BPA-NPs could be
      preferentially internalized by Hela cells, owing to their specific interaction
      between biotin and overexpressed biotin receptors. In addition, DI-BPA-NPs
      effectively inhibited Hela cell proliferation by inducing G2/M phase cycle arrest
      and decreasing the intracellular reactive oxygen species (ROS) level by 31.50 +/-
      2.29% in 5 min. In summary, DI-BPA-NPs shows improved antiproliferative activity
      against human cervical cancer as comparing with free DI, demonstrating its
      application potential in cancer therapy.

PMID- 30102530
TI  - Cellular Small Molecules Contribute to Twister Ribozyme Catalysis.
AB  - The number of self-cleaving small ribozymes has increased sharply in recent
      years. Advances have been made in describing these ribozymes in terms of four
      catalytic strategies: alpha describes in-line attack, beta describes
      neutralization of the nonbridging oxygens, gamma describes activation of the
      nucleophile, and delta describes stabilization of the leaving group. Current
      literature presents the rapid self-cleavage of the twister ribozyme in terms of
      all four of these classic catalytic strategies. Herein, we describe the
      nonspecific contribution of small molecules to ribozyme catalysis. At biological
      pH, the rate of the wild-type twister ribozyme is enhanced up to 5-fold in the
      presence of moderate buffer concentrations, similar to the 3-5-fold effects
      reported previously for buffer catalysis for protein enzymes. We observe this
      catalytic enhancement not only with standard laboratory buffers, but also with
      diverse biological small molecules, including imidazole, amino acids, and amino
      sugars. Bronsted plots suggest that small molecules assist in proton transfer,
      most likely with delta catalysis. Cellular small molecules provide a simple way
      to overcome the limited functional diversity of RNA and have the potential to
      participate in the catalytic mechanisms of many ribozymes in vivo.

PMID- 30102529
TI  - Gastrointestinal Fate of Fluid and Gelled Nutraceutical Emulsions: Impact on
      Proteolysis, Lipolysis, and Quercetin Bioaccessibility.
AB  - Fluid and gelled nutraceutical emulsions were formulated from quercetin-loaded
      caseinate-stabilized emulsions by the addition of gellan gum with or without
      acidification with glucono-delta-lactone. Gellan gum addition increased the
      viscosity or gel strength of the fluid and gelled emulsions, respectively. The
      behavior of the nutraceutical emulsions in a simulated gastrointestinal tract
      depended upon their initial composition. Fluid emulsions containing different
      gellan gum levels (0-0.2%) had similar protein and lipid hydrolysis rates as well
      as similar quercetin bioaccessibility (~51%). Conversely, proteolysis, lipolysis,
      and quercetin bioaccessibility decreased with an increasing gellan gum level in
      the gelled emulsions. In comparison to gelled emulsions, fluid emulsions were
      digested more rapidly and led to higher quercetin bioaccessibility. There was a
      good correlation between quercetin bioaccessibility and the lipolysis rate. These
      findings are useful for designing nutraceutical-loaded emulsions that can be used
      in a wide range of food products with different rheological properties.

PMID- 30102531
TI  - Selective Electrochemical Separation and Recovery of Uranium from Mixture of
      Uranium(VI) and Lanthanide(III) Ions in Aqueous Medium.
AB  - Separation of uranium (U) from interfering lanthanide ions (Ln3+) in aqueous
      medium is important in view of sustainable nuclear power production and
      remediation of radioactive waste. Separation of U in aqueous medium by
      electrochemical means is still unexplored. Herein, we report electrochemical
      separation of U from interfering lanthanides ions in 0.1 M KCl on poly(3,4
      ethylenedioxythiophene) poly(styrenesulfonate) modified platinum (PEDOT:PSS/Pt)
      electrode. U in solution commonly exists as uranyl (UO22+). U separation is
      achieved in a two step process: (i) UO22+ reduction to insoluble urania (UO2)
      which gets deposited on PEDOT:PSS/Pt in the presence of Ln3+ (La3+, Ce3+, and
      Sm3+) ions and (ii) oxidation of electrodeposited UO2 to UO22+ in fresh 0.1 M KCl
      (pH = 2) solution. Electrodeposition of UO2 is confirmed by X-ray photoelectron
      spectroscopy (XPS), X-ray diffraction (XRD), and scanning electron microscopy
      (SEM). Although, the presence of Ln3+ ions in UO22+solution hinders
      electrodeposition of UO2, but application of more negative reduction potential (
      0.6 V vs Ag/AgCl) for longer duration (8 h) results in quantitative
      electrodeposition of UO2. Inductively coupled plasma mass spectrometry (ICP-MS)
      shows that 94% (+/-10%) recovery of UO22+ is possible from mixed solution of
      UO22+and Ln3+ ions on PEDOT:PSS/Pt electrode.

PMID- 30102532
TI  - Monolithic 3D Cross-Linked Polymeric Graphene Materials and the Likes:
      Preparation and Their Redox Catalytic Applications.
AB  - While there have been tremendous studies about graphene and its applications in
      the past decade, so far the proposed huge potential of this material has not been
      materialized. One of the prerequisites to overcome these challenges is
      maintaining the nature and intrinsic properties of individual graphene sheets
      while in the state of bulk material. Thus, in this Perspective contribution, the
      fabrication/synthesis of the monolithic polymeric and three-dimensional (3D)
      cross-linked bulk materials (3DGraphene) with (doped) 2D graphene sheets as the
      building block will first be briefly summarized. Then, the second part will cover
      the redox catalytic application of these bulk materials including doped
      3DGraphene, the graphene-like material polymeric C3N4 and their hybrid materials.
      These will include mainly oxygen reduction reactions (ORR), hydrogen evolution
      reactions (HER), and CO2 reduction for their latest development. Finally,
      challenges and outlook related to the design of 3D cross-linked graphene based
      materials and their catalytic applications will be briefly discussed.

PMID- 30102533
TI  - Dynamic Kinetic Asymmetric Heck Reaction for the Simultaneous Generation of
      Central and Axial Chirality.
AB  - A highly diastereo- and enantioselective, scalable Pd-catalyzed dynamic kinetic
      asymmetric Heck reaction of heterobiaryl sulfonates with electron-rich olefins is
      described. The coupling of 2,3-dihydrofuran or N-boc protected 2,3-dihydropyrrole
      with a variety of quinoline, quinazoline, phthalazine, and picoline derivatives
      takes place with simultaneous installation of central and axial chirality,
      reaching excellent diastereo- and enantiomeric excesses when in situ formed
      [Pd0/DM-BINAP] was used as the catalyst, with loadings reduced down to 2 mol % in
      large scale reactions. The coupling of acyclic, electron-rich alkenes can also be
      performed using a [Pd0/Josiphos ligand] to obtain axially chiral heterobiaryl
      alpha-substituted alkenes in high yields and enantioselectivities. Products from
      Boc-protected 2,3-dihydropyrrole can be easily transformed into N, N ligands or
      appealing axially chiral, bifunctional proline-type organocatalysts.
      Computational studies suggest that a beta-hydride elimination is the
      stereocontrolling step, in agreement with the observed stereochemical outcome of
      the reaction.

PMID- 30102534
TI  - Total Synthesis and Structure Revision of Palmarumycin B6.
AB  - Palmarumycin B6 and its regioisomer were synthesized via 7- and 13-step routes
      using 2-chlorophenol and 4-chlorophenyl methyl ether as the starting materials in
      overall yields of 2.7% and 12%, respectively. Their structures were characterized
      by 1H and 13C NMR, HRESIMS, and X-ray diffraction data. The structure of
      palmarumycin B6 was revised as 6-chloropalmarumycin CP17. The bioassay results
      showed that the larvicidal activity of palmarumycin B6 with an LC50 value of 32.7
      MUM was significantly higher than that of its 8-chloro isomer, with an LC50 value
      of 227.3 MUM.

PMID- 30102535
TI  - Infrared Spectroscopic and Theoretical Studies of Group 3 Metal Isocyanide
      Molecules.
AB  - A series of group 3 metal isocyanide complexes were prepared via the reactions of
      laser ablated scandium, yttrium, and lanthanum atoms with (CN)2 in an argon
      matrix. The product structures were identified on the basis of their
      characteristic infrared absorptions from isotopically labeled (CN)2 samples as
      well as the calculated frequencies and isotopic frequency ratios. Group 3 metal
      atoms reacted with (CN)2 to form M(NC)2 (M = Sc, Y, La) when the samples were
      subjected to lambda > 220 nm irradiation. Other products such as M(NC)3 and MNC
      were produced together with M(NC)2 through either the reactions of M(NC)2 and
      (CN)2 or the loss of one CN ligand from M(NC)2. CCSD(T)//B3LYP calculations
      reveal that ScNC possesses a 3Delta ground state, while 1Sigma+ is most stable
      for YNC and LaNC. All of the M(NC)2 and M(NC)3 complexes were predicted to have
      doublet and singlet ground states, respectively. Group 3 metal cyanides are less
      stable than the isocyanides by at least 4 kcal/mol at the CCSD(T) level, and
      their C-N stretches are much weaker than the N-C stretches of the isocyanides. No
      absorption can be assigned to the M(CN) x complex, which would appear between
      2100 and 2250 cm-1.

PMID- 30102536
TI  - Facile Synthesis of pi-Conjugated Quinazoline-Substituted Ethenes from 2
      Ethynylanilines and Benzonitriles under Transition-Metal-Free Conditions.
AB  - A new transition-metal-free version for the synthesis of pi-conjugated
      quinazoline-substituted ethene derivatives from readily available starting
      materials has been developed. Quinazoline-substituted ethenes were obtained in
      moderate to high yields with completely Z-selectivity, and the resulting
      quinazoline-substituted ethenes show typical aggregation-induced emission (AIE)
      properties.

PMID- 30102537
TI  - How Different Are the Characteristics of Aqueous Solutions of tert-Butyl Alcohol
      and Trimethylamine- N-Oxide? A Molecular Dynamics Simulation Study.
AB  - Atomistic molecular dynamics simulations have been used to investigate
      differences in the characteristics of the aqueous solutions of two structurally
      similar, biologically important molecules, namely, tert-butyl alcohol (TBA) and
      trimethylamine- N-oxide (TMAO). By analyzing radial distribution functions,
      preferential solvation factors, and the number of nearest neighbors, structural
      characteristics of the two aqueous solutions are found to be dramatically
      different. By examining the distribution of nearest neighbor solute and solvent
      molecules in these two solutions, it is found that the aqueous solution of TMAO
      is homogeneous, whereas that of TBA is not. Further scrutiny of TBA-TBA radial
      distribution function at a high concentration by splitting the surrounding TBA
      molecules into two hemispheres demonstrates that the TBA aggregation occurs not
      only from the side of methyl moieties of TBA as expected in hydrophobicity
      induced aggregation, but also from the side of the polar C-OH group. To analyze
      the effect of concentration of the two solute molecules (TBA and TMAO) on the
      local structure of water, tetrahedral order parameter and distributions of
      tetrahedral angles and hydrogen-bonding angles have been calculated for both the
      solutions. It is surprising to see that at high concentrations, the local water
      structure in the TMAO solution is more disrupted compared to the same in the TBA
      solution. Finally, the action of these two solutes on the folding-unfolding
      behavior of Trp-cage miniprotein has been analyzed and their contrasting
      activities toward the protein stability are correlated to the strikingly
      different behavior of their aqueous solutions.

PMID- 30102538
TI  - Metalloporphyrin-Catalyzed Oxidation of Sunitinib and Pazopanib, Two Anticancer
      Tyrosine Kinase Inhibitors: Evidence for New Potentially Toxic Metabolites.
AB  - Oxidation of two tyrosine kinase inhibitors (TKIs) sunitinib and pazopanib, using
      a chemical catalytic system able to mimic the cytochrome P450 type oxidation,
      allowed us to prepare  putative reactive/toxic metabolites of these anticancer
      drugs. Among these metabolites, aromatic aldehyde derivatives were unambiguously
      characterized. Such biomimetic oxidation of TKI-type drugs was essential to
      facilitate the identification of low amounts of aldehydes generated from these
      TKIs when incubated with human liver microsomes (HLM), which are classical models
      of human hepatic metabolism. These TKI derivative aldehydes quickly react in
      vitro with amines. A similar reaction is expected to occur in vivo and may be at
      the origin of the potentially severe hepatotoxicity of these TKIs.

PMID- 30102539
TI  - Sparsity Facilitates Chemical-Reaction Selection for Engine Simulations.
AB  - Analysis of large-scale, realistic models incorporating detailed chemistry can be
      challenging because each simulation is computationally expensive, and a complete
      analysis may require many simulations. This paper addresses one such problem of
      this type, chemical-reaction selection in engine simulations. In this
      computationally challenging case, it is demonstrated how the important concept of
      sparsity can facilitate chemical-reaction selection, which is the process of
      finding the most important chemical reactions for modeling a chemical process. It
      is difficult to perform accurate reaction selection for engine simulations using
      realistic models of the chemistry, as each simulation takes processor weeks to
      complete. We developed a procedure to efficiently accomplish this selection
      process with a relatively small number of simulations using a form of global
      sensitivity analysis based on sparse regression. The chemical-reaction selection
      leads to an analysis of the ignition chemistry as it evolves within the
      compression-ignition engine simulations and allows for the spatial development of
      the selected chemical reactions to be studied in detail.

PMID- 30102540
TI  - Anisotropic Optoelectronic Properties of Melt-Grown Bulk CsPbBr3 Single Crystal.
AB  - All-inorganic perovskite CsPbBr3 has been considered as one of the star
      semiconductors due to its inspiring optoelectronic properties and higher
      stability than the organic-inorganic hybrid counterparts. The preparation of
      large-size single crystals with low trap density and the performance optimization
      on the devices still challenge the commercial application of this material. Here
      the large transparent CsPbBr3 single crystal (phi 24 mm * 90 mm) was grown by a
      modified Bridgman method. With the determination of crystallographic directions,
      the anisotropic optoelectronic properties were investigated for the first time.
      The result shows a high electron mobility (11.61 cm2/(V s)) along the b axis, one
      order of magnitude higher than that along the c axis. Moreover, the photoresponse
      measurement yields a high responsivity (5.83 A/W) and external quantum efficiency
      (1360%) on the (001) plane irradiated by the 532 nm laser diode with 1 mW/cm2
      under 10 V bias, which is a 305% enhancement compared with the (010) plane. Our
      study on anisotropic optoelectronic properties of CsPbBr3 will provide a
      significant approach to enhance the performance of single-crystalline devices.

PMID- 30102541
TI  - Mechanical Anisotropy in GNNQQNY Amyloid Crystals.
AB  - Mapping the nanomechanical properties of amyloids can provide valuable insights
      into structure and assembly mechanisms of protein aggregates that underlie the
      development of various human diseases. Although it is well-known that amyloids
      exhibit an intrinsic stiffness comparable to that of silk (1-10 GPa), a detailed
      understanding of the directional dependence (anisotropy) of the stiffness of
      amyloids and how it relates to structural features in these protein aggregates is
      missing. Here we used steered molecular dynamics (SMD) simulations and amplitude
      modulation-frequency modulation (AM-FM) atomic force microscopy to measure the
      directional variation in stiffness of GNNQQNY amyloid crystals. We reveal that
      individual crystals display significant mechanical anisotropy and relate this
      anisotropy to subtle but mechanically important differences in interactions
      between interfaces that define the crystal architecture. Our results provide
      detailed insights into the structure-mechanics relationship of amyloid that may
      help in designing amyloid-based nanomaterials with tailored mechanical
      properties.

PMID- 30102542
TI  - Optical Properties and Kinetics: New Insights to the Porphyrin Assembly and
      Disassembly by Polarized Resonance Synchronous Spectroscopy.
AB  - With their unique photochemical properties, porphyrins have remained for decades
      the most interested chemicals as photonic materials for applications ranging from
      chemistry, biology, medicine, to photovoltaic. Porphyrins can self-assemble into
      higher order structures. However, information has been scant on the kinetics and
      structural evolution during porphyrin assembly and disassembly. Furthermore,
      quantitative understanding of the porphyrin optical activities is complicated by
      the complex interplay of photon absorption, scattering, and fluorescence emission
      that can concurrently occur in porphyrin samples. Using meso-tetrakis(4
      sulfonatophenyl)porphyrin as the model molecule, reported herein is a combined UV
      vis extinction, polarized Stokes-shifted fluorescence, and polarized resonance
      synchronous spectroscopic (PRS2) study of porphyrin assembly and disassembly in
      acidic solutions. Although porphyrin assembly and disassembly occur
      instantaneously upon the sample preparation, both processes last at least a few
      months before reaching their approximate equilibrium states. The two processes
      were monitored in situ by quantifying the porphyrin fluorescence and scattering
      depolarizations as well as its extinction, absorption, scattering, and
      fluorescence emission cross sections. In addition to a series of new insights to
      the porphyrin assembly and disassembly, the methodology described in this work
      opens the door for the in situ study of the structural and optical properties of
      photonic materials comprising molecular assembly.

PMID- 30102543
TI  - Synthesis of Benzo[1,6]naphthyridinones Using the Catellani Reaction.
AB  - An intramolecular version of the Catellani reaction was optimized for one-step
      synthesis of bulky N-substituted benzo[1,6]naphthyridinones with good to
      excellent yields. The optimized reaction of N-substituted o-bromobenzamides with
      4-bromoquinolines features a wide substrate scope and yields of up to 98%. The
      employment of aryl bromides under carefully optimized conditions instead of the
      usual aryl iodides enhances the scope of the reaction.

PMID- 30102545
TI  - Time Evolution of Precursor Thin Film of Water on Polyelectrolyte Brush.
AB  - The microscopic wetting behavior of a water film on the line-patterned surface of
      a polyelectrolyte brush was directly visualized using an optical microscope by
      dyeing procedures. Surface line patterns of 5 and 5 MUm width or 10 and 5 MUm
      width for the polyelectrolyte brush and hydrophobic monolayer, respectively, were
      prepared by a photolithography process, chemical vapor adsorption method, and
      surface-initiated polymerization. A droplet of water containing dye was placed on
      the line-patterned surface. In front of the contact line, a water film with a
      nanometer-scale thickness, referred to as a precursor film, elongated along the
      polymer brush line with time. The elongation velocity at the first stage
      increased as the brush line width increased. On the other hand, at the second
      stage after the macroscopic contact line stopped moving, the precursor film
      continued to elongate in proportion to the 0.6 power of time, independent of the
      brush thickness, line width, and droplet volume.

PMID- 30102544
TI  - Entrapment and Dissolution of Microbubbles Inside Microwells.
AB  - The formation and evolution of immersed surface micro- and nanobubbles are
      essential in various practical applications, such as the usage of
      superhydrophobic materials, drug delivery, and mineral flotation. In this work,
      we investigate the entrapment of microbubbles on a hydrophobic surface,
      structured with microwells, when water flow passes along, and the subsequent
      microbubble dissolution. At entrapment, the microbubble is initially pinned at
      the edge of the microwell. At some point, the three-phase contact line detaches
      from one side of the edge and separates from the wall, after which it further
      recedes. We systematically investigate the evolution of the footprint diameter
      and the contact angle of the entrapped microbubbles, which reveals that the
      dissolution process is in the constant contact angle mode. By varying the gas
      undersaturation level, we quantify how a high gas undersaturation enhances the
      dissolution process, and compare with simplified theoretical predictions for
      dissolving bubbles on a plane surface. We find that geometric partial blockage
      effects of the diffusive flux out of the microbubble trapped in the microwell
      lead to reduced dissolution rates.

PMID- 30102546
TI  - Copper-Catalyzed Oxidative Cleavage of Electron-Rich Olefins in Water at Room
      Temperature.
AB  - A copper-catalyzed oxidative cleavage of electron-rich olefins into their
      corresponding carbonyl derivatives is described as an alternative to ozonolysis.
      The scope includes various precursors to aryl ketone derivatives, as well as
      oxidations of enol ethers bearing atypical alkyl and dialkyl substitution, the
      first of their kind among such metal catalyzed alkene cleavage reactions. The use
      of an inexpensive copper salt, room temperature conditions, an aerobic
      atmosphere, and water as the global reaction medium highlight the green features
      of this new method. Associated mechanistic investigations are also presented.

PMID- 30102547
TI  - One-Pot Intermolecular Reductive Cross-Coupling of Deactivated Aldehydes to
      Unsymmetrically 1,2-Disubstituted Alkenes.
AB  - The phospha-Peterson reaction between a lithiated secondary phosphane,
      MesP(Li)TMS, and an aldehyde affords Mes-phosphaalkenes which, upon methanol
      addition and P-oxidation, react with a second carbonyl compound site specifically
      to produce unsymmetric alkenes. The E/ Z selectivity of the one-pot cross
      coupling is largely determined by the electronic nature of the aryl substituent
      of the first aldehyde, with electron-donating groups giving rise to increased
      amounts of Z-alkenes.

PMID- 30102548
TI  - Chiral Lead Halide Perovskite Nanowires for Second-Order Nonlinear Optics.
AB  - Hybrid organic/inorganic lead halide perovskites (LHPs) have recently emerged as
      extremely promising photonic materials. However, the exploration of their optical
      nonlinearities has been mainly focused on the third- and higher-order nonlinear
      optical (NLO) effects. Strong second-order NLO responses are hardly expected from
      ordinary LHPs due to their intrinsic centrosymmetric structures, but are highly
      desirable for advancing their applications in the next generation integrated
      photonic circuits. Here we demonstrate the fabrication of a novel
      noncentrosymmetric LHP material by introducing chiral amines as the organic
      component. The nanowires grown from this new LHP material crystallize in a
      noncentrosymmetric P1 space group and demonstrate highly efficient second
      harmonic generation (SHG) with high polarization ratios and chiroptical NLO
      effects. Such a chiral perovskite skeleton could provide a new platform for
      future engineering of optoelectronic functionalities of hybrid perovskite
      materials.

PMID- 30102549
TI  - Interaction of the Saponin Aescin with Ibuprofen in DMPC Model Membranes.
AB  - In the present work, we study the interaction of the saponin aescin with the
      nonsteroidal anti-inflammatory drug (NSAID) ibuprofen at concentrations of 1.2
      2.5 mM. These amounts are higher than those usually used for medication (10-300
      MUM) to show possible structures and formulations for orally absorbed drug
      delivery systems. It is shown how the interaction of both substances, separately
      or together, alters the thermotropic phase behavior of the 1,2-dimyristoyl- sn
      glycero-3-phosphocholine (DMPC) bilayer in the presence of different amounts of
      aescin, ranging from 20 MUM to 1 mM. The methods of choice are differential
      scanning calorimetry (DSC), and additionally wide-angle (WAXS) and small-angle X
      ray scattering (SAXS). We found that these two additives, aescin and ibuprofen,
      alter the temperature-dependent structural appearance of the DMPC membrane
      depending on the aescin and drug content. The presence of the saponin and the
      drug become visible on different length scales, i.e., ranging from a global
      structural change to inner-membrane interactions. DSC reveals that the drug and
      saponin alter the cooperativity of the DMPC phase transition in a concentration
      dependent manner. Furthermore, there is a significant difference between the drug
      containing compared to the drug-free systems. By WAXS, we could resolve that
      aescin reverses the strong impact of ibuprofen on the diffraction peak of DMPC.
      Both molecules interact strongly with the phospholipid headgroups. This becomes
      visible in a changing area per lipid and shifting phase transition to higher
      temperatures. SAXS experiments reveal that the addition of ibuprofen leads to
      major morphological changes in the phospholipid bilayer. SAXS experiments
      performed on representative samples do not only cover the drug-saponin
      interaction within the bilayer from the structural perspective but also confirm
      the visually observed macroscopic concentration and temperature-dependent phase
      behavior. Vesicular shape of extruded samples is conserved at low aescin
      contents. At intermediate aescin content, aggregation between vesicles occurs,
      whereby the strength of aggregation is reduced by ibuprofen. At high aescin
      contents, DMPC bilayers are solubilized. The kind of formed structures depends on
      temperature and drug content. At low temperature, separated bilayer sheets are
      formed. Their size increases with ibuprofen in a concentration-dependent manner.
      At high temperature, the drug-free system reorganizes into stacked sheets.
      Whereas sheets at 5 mol % ibuprofen close to vesicles, the ones with 10 mol % of
      the drug increase massively in size. Altogether, ibuprofen was found to rather
      enhance than inhibit structural and thermotropic membrane modifications induced
      by the aescin on the DMPC model membrane.

PMID- 30102550
TI  - Nature of Hexagonal Silicon Forming via High-Pressure Synthesis: Nanostructured
      Hexagonal 4H Polytype.
AB  - Hexagonal Si allotropes are expected to enhance light absorption in the visible
      range as compared to common cubic Si with diamond structure. Therefore, synthesis
      of these materials is crucial for the development of Si-based optoelectronics. In
      this work, we combine in situ high-pressure high-temperature synthesis and vacuum
      heating to obtain hexagonal Si. High pressure is one of the most promising routes
      to stabilize these allotropes. It allows one to obtain large-volume
      nanostructured ingots by a sequence of direct solid-solid transformations,
      ensuring high-purity samples for detailed characterization. Thanks to our
      synthesis approach, we provide the first evidence of a polycrystalline bulk
      sample of hexagonal Si. Exhaustive structural analysis, combining fine-powder X
      ray and electron diffraction, afforded resolution of the crystal structure. We
      demonstrate that hexagonal Si obtained by high-pressure synthesis correspond to
      Si-4H polytype (ABCB stacking) in contrast with Si-2H (AB stacking) proposed
      previously. This result agrees with prior calculations that predicted a higher
      stability of the 4H form over 2H form. Further physical characterization,
      combining experimental data and ab initio calculations, have shown a good
      agreement with the established structure. Strong photoluminescence emission was
      observed in the visible region for which we foresee optimistic perspectives for
      the use of this material in Si-based photovoltaics.

PMID- 30102551
TI  - Mind the Gap: From Tool to Knowledge Base.
AB  - With the ethical, legal, and societal issues (ELSI) Knowledge Base, we introduce
      a key element of the Biobanking and Biomolecular Resources Research
      Infrastructure-European Research Infrastructure Consortium (BBMRI-ERIC) Common
      Service ELSI, which provides ethical, legal, and societal support for researchers
      and biobankers involved in transnational research. In contrast to the customized
      support provided by the ELSI Helpdesk, the ELSI Knowledge Base will be available
      to the user on a self-serve basis. The information that is made available through
      a knowledge base comes from multiple sources, usually from several expert
      contributors who are well versed in the subject matter. The knowledge base
      provides users with a first orientation on the subject matter, as well as
      allowing them to explore more detailed information if desired in a self-service
      manner. It is crucial that the information and knowledge provided are shared in a
      manner that is user friendly. Long lists of links, legalistic language, and
      multiple links have to be avoided wherever possible. The long-term sustainability
      and accuracy of a knowledge base need to be ensured by placing its expert
      curation and technical maintenance under the responsibility of an organization
      rather than a research consortium. In its core, it builds on a scenario-based
      approach using a nonlegalistic language. In addition, the knowledge base connects
      to frequently asked questions, promotes contract and informed consent templates,
      how-to-guides, best-practice models, and scripts. The ELSI Knowledge Base is a
      key element of the BBMRI-ERIC Common Service ELSI, which currently serves
      biobanks but will be enlarged to serve the biological and medical sciences
      community. In contrast to the ELSI Helpdesk, which provides customized support,
      the ELSI Knowledge Base is available to the user on a self-serve basis. The
      conceptualization of the ELSI Knowledge Base builds on assessments of several
      ethical, legal, and societal guidance tools that favor a single sustainable
      knowledge base for closing the knowledge gap by providing practical hands-on
      guidance for researchers. Ultimately, the ELSI Knowledge Base aims at promoting
      practical know-how and skills for conducting responsible research.

PMID- 30102552
TI  - Transcatheter arterial embolization of acute bleeding as 24/7 service: predictors
      of outcome and mortality.
AB  - OBJECTIVE: To analyze times of occurrence and identify risk factors (RFs) for
      technical and clinical failure and mortality of transcatheter arterial
      embolization (TAE) of acute bleeding in a major hospital. METHODS: All TAEs
      performed at our hospital from 2006 to 2013 (n = 327) were retrospectively
      analyzed. RESULTS: TAEs were performed during regular weekday hours in 165 (50%)
      and during off-hours in 162 (50%) cases. With 40 regular and 128 off-hours/week,
      3.25 times more TAEs were performed during regular hours. There was an even
      distribution across weekdays (Mon-Fri:16.9 +/- 1.5%), while fewer TAEs were
      performed on weekends (Sat: 8.3%, Sun: 7.3%). Technical success of TAEs was 93.9%
      with a clinical success of 79.2% and a 30-day mortality of 18.4%. Shock was an RF
      for technical failure (p = 0.022). RFs for clinical failure were low hemoglobin
      (Hb) (p = 0.021) and transfusion of >=6 units packed cells (p = 0.009).
      Independent RFs for mortality were clinical failure (p < 0.001), coagulopathy (p
      = 0.005), and shock (p < 0.001). CONCLUSION: Our results provide no evidence for
      a subjectively perceived increase in TAEs during off-hours but rather appear to
      show that most TAEs are performed during regular hours. Prompt TAE to control
      acute bleeding is crucial to prevent a drop in Hb with shock and the need for
      transfusion, which may promote coagulopathy and rebleeding, all of which are risk
      factors for a negative outcome. ADVANCES IN KNOWLEDGE: The presented analysis
      provides insights of occurrences and risk factors for success of transcatheter
      arterial embolization in acute bleeding in a large study population.

PMID- 30102554
TI  - Letter to editor on "Comparison of panoramic radiography and cone beam CT in the
      assessment of juxta-apical radiolucency".

PMID- 30102553
TI  - Intended Hydration Strategies and Knowledge of Exercise-Associated Hyponatraemia
      in Marathon Runners: A Questionnaire-Based Study.
AB  - CONTEXT:   Exercise-associated hyponatremia (EAH) is a potentially fatal
      condition that can be prevented by avoiding excessive fluid intake. Running has
      become more popular in recent years, so it is important to assess the safety of
      runners' hydration strategies. OBJECTIVE:   (1) To explore the intended hydration
      strategies of a sample of marathon runners before the 2014 London Marathon, (2)
      to examine their sources of information and knowledge about fluid intake and
      their understanding of EAH, and (3) to compare these findings with the results of
      a similar study carried out before the 2010 London Marathon. DESIGN:   Cross
      sectional study. SETTING:   The 2014 London Marathon. PATIENTS OR OTHER
      PARTICIPANTS:   A total of 298 runners (148 males, 150 females), 0.83% of all
      race finishers. MAIN OUTCOME MEASURE(S):   Planned frequency, type, and volume of
      hydration; sources of information about appropriate drinking; and understanding
      of hyponatremia were explored. Comparisons were made with data collected from a
      sample of participants at the 2010 London Marathon. Data relating to the 2014
      cohort are presented in descriptive form. Comparisons of the 2010 and 2014
      cohorts were conducted using parametric and nonparametric methods. RESULTS:   A
      total of 48.7% of the 2014 cohort listed drinking to thirst as the most important
      factor affecting their hydration strategy during the race. This compared with
      25.3% of runners from the 2010 cohort and represented an increase (chi2 = 29.1, P
      = .001); 5.8% of the 2014 cohort planned on drinking more than 3.5 L, compared
      with 12% of the 2010 cohort (chi2 = 4.310, P = .038). CONCLUSIONS:   The number
      of sampled individuals using thirst to guide hydration strategies in the 2014
      London Marathon increased from 2010. However, more than half of the 2014 cohort
      was not planning to drink to thirst. Runners still need to be educated about the
      risks of overdrinking as they continue to demonstrate a lack of knowledge and
      understanding.

PMID- 30102555
TI  - Ovarian cancer screening-ultrasound; impact on ovarian cancer mortality.
AB  - Although ovarian cancer (OC) is the most lethal of all female malignancies,
      debate still exists concerning the benefits and harms of the screening programs
      and their impact on long-term survival and mortality from the disease. The most
      widely tested screening strategies have focused on transvaginal ultrasound (TVU)
      and on algorithms that measure serum levels or interval changes of cancer antigen
      125 (CA-125) either individually or in combination. Transvaginal ultrasound can
      identify size and morphology changes of the ovary that may signal a developing
      malignancy; yet, it is still accused of having a low specificity. There is
      preliminary evidence that screening can improve survival, but the impact of
      screening on mortality from OC is still unclear and warrants further validation.
      In spite of having many published prospective studies, up to-date, none have been
      able to demonstrate conclusively a reduction in mortality from OC both in the
      screened general or high-risk population. Data from the US Prostate, Lung,
      Colorectal and Ovarian (PLCO) Cancer Screening Trial has not shown survival or
      mortality benefits in the general population. Most prospective trials have
      reported a decrease in stage at detection (with the exception of the PLCO trial),
      thereby allowing treatment to be initiated when the disease is most curable.
      Research is in progress to develop new diagnostic tests and novel biomarkers,
      which when used in combination can increase the accuracy and outcomes of
      screening. In this review article, we will discuss the debate provoked on OC
      screening programs and the impact of using ultrasound on the reduction of OC
      related mortality.

PMID- 30102556
TI  - Identification and Multilineage Potential Research of a Novel Type of Adipose
      Derived Mesenchymal Stem Cells from Goose Inguinal Groove.
AB  - Adipose tissue-derived mesenchymal stem cells (ADSCs) play a crucial role in the
      field of regenerative medicine and tissue repair for its own unique features.
      However, up to date, the isolation and characterizations of multidifferentiation
      potentials of goose ADSCs are still uncertain. In this study, we successfully
      isolated ADSCs from goose inguinal groove in vitro for the first time and also
      attempted to unravel its fundamental differentiation potentials and genetic
      characteristics. The results showed that isolated ADSCs exhibited a typical
      fibroblast-like morphology and high proliferative potential, could be passaged
      for at least 40 passages and maintained high hereditary stability with more than
      92.2% of cells were diploid (2n = 78) by G-banding analysis. Moreover, the ADSCs
      could express pluripotent marker gene (OCT4) and mesenchymal stem cells-related
      surface antigens, which are similar to previously reported human ADSCs.
      Additionally, the goose ADSCs could be induced to transdifferentiate into cells
      of three layers in vitro, such as osteoblasts, chondrocytes, and adipocytes
      derived from mesoderm, neurocytes from ectoderm, and hepatocytes of the endoderm.
      Most of all, we confirmed that the induced beta-like cells and hepatocytes had
      metabolic functions similar to normal cells in vivo. Taken together, these
      results demonstrated the multidifferentiation potentials of ADSCs in vitro, which
      conferred an appealing candidate for cell regenerative therapy.

PMID- 30102557
TI  - Theranostics in neuroendocrine tumours: somatostatin receptor imaging and
      therapy.
AB  - Theranostics and its principles: pre-treatment selection of patients who are most
      likely to benefit from treatment by the use of a related, specific diagnostic
      test are integral to the treatment of patients with neuroendocrine tumours
      (NETs). This is due to NETs' important, but variable, somatostatin receptor
      (SSTR) expression, their heterogeneity and variation in site of primary and rate
      of progression. Only patients whose tumours have sufficient expression of SSTRs
      will benefit from SSTR-based radionuclide therapy and demonstrating this
      expression prior to therapy is essential. This article provides a relevant
      overview of NETs and the multiple facets of SSTR based theranostics, including
      imaging and therapy radionuclides; clinical efficacy and toxicity; patient
      selection and treatment and finally emerging radiopharmaceuticals and newer
      clinical applications.

PMID- 30102558
TI  - Review of risk factors of secondary cancers among cancer survivors.
AB  - Improvements in cancer survival have made the long-term risks from treatments
      more important, in particular among the children, adolescents and young adults
      who are more at risk particularly due to a longer life expectancy and a higher
      sensitivity to treatments. Subsequent malignancies in cancer survivors now
      constitute 15 to 20% of all cancer diagnoses in the cancer registries. Lots of
      studies are published to determine risk factors, with some controversial
      findings. Just data from large cohorts with detailed information on individual
      treatments and verification of what is called "secondary cancers" can add some
      knowledge, because their main difficulty is that the number of events for most
      second cancer sites are low, which impact the statistical results. In this review
      of the literature, we distinguish second and secondary cancers and discuss the
      factors contributing to this increased risk of secondary cancers. The article
      concludes with a summary of current surveillance and screening recommendations.

PMID- 30102559
TI  - Understanding treatment guidelines with bismuth and non-bismuth quadruple
      Helicobacter pylori eradication therapies.
AB  - INTRODUCTION: Recent Helicobacter pylori treatment guidelines recommend the 4
      drug combinations bismuth quadruple therapy and concomitant therapy. Areas
      covered: We review antimicrobial therapy for H. pylori in the context of
      antimicrobial therapy in general and specifically in relation to good
      antimicrobial stewardship (defined as optimal selection, dose, and duration of an
      antimicrobial that results in the best clinical outcome for the treatment of
      infection, with minimal toxicity to the patient and minimal impact on subsequent
      resistance). Expert commentary: The lack of regional and local H. pylori
      susceptibility data prevents implementation of susceptibility-based antimicrobial
      therapy and forces compromises. Bismuth quadruple therapy employing at least
      1,500 mg of metronidazole for 14 days is effective despite metronidazole
      resistance. The main drawback is side effects causing reduced adherence. Versions
      where amoxicillin replaces metronidazole or tetracycline also appear effective.
      It is likely that bismuth quadruple therapy can be simplified by giving bismuth
      and possibly tetracycline b.i.d., possibly with fewer side effects. Concomitant
      therapy (a proton pump inhibitor, metronidazole, clarithromycin, amoxicillin) is
      ineffective with dual clarithromycin-metronidazole resistance and all patients
      receive at least one unnecessary antibiotic thus promoting antimicrobial
      resistance worldwide. Concomitant therapy should be abandoned when susceptibility
      testing becomes widespread or an alternate becomes available.

PMID- 30102560
TI  - Congenital anomalies of the pulmonary arteries: an imaging overview.
AB  - Congenital pulmonary artery anomalies represent a diverse group of abnormalities,
      ranging from asymptomatic incidental findings to causes of sudden cardiac death.
      While some may be recognized in childhood, others may be found incidentally in
      adulthood. We review the clinical and imaging findings in patients with
      congenital anomalies of the pulmonary arteries, including valvular and
      perivavular anomalies as well as abnormal narrowing, course and communications of
      the pulmonary arteries. We also discuss the role of various imaging modalities in
      the evaluation of these patients. It is vital to be aware of the key radiologic
      manifestations and associated haemodynamic consequences in these conditions in
      order to facilitate accurate diagnosis and prognostic stratification.

PMID- 30102561
TI  - National survey of imaging practice for suspected or confirmed plasma cell
      malignancies.
AB  - OBJECTIVE:: Cross-sectional imaging is now recommended by the National Institute
      for Health and Care Excellence (NICE) for patients with suspected and newly
      diagnosed myeloma instead of skeletal survey. The objectives of this study were:
      (1) To evaluate compliance of current UK imaging practice with reference to
      National Institute for Health and Care Excellence best-practice clinical
      guidelines for plasma cell malignancies. (2) To identify factors which may
      influence diagnostic imaging choices. METHODS:: We conducted a national online
      survey to assess compliance with guidelines and to identify challenges to
      implementation (endorsed by Myeloma UK, UK Myeloma Forum and the British Society
      of Skeletal Radiologists). RESULTS:: Responses were received from 31 district
      general and 28 teaching hospitals. For suspected and confirmed myeloma, skeletal
      survey remained the most frequent first-line imaging test (suspected myeloma
      44.3%, confirmed myeloma 37.7%). Only 9.8 % of responders offered first-line
      whole body MRI. CONCLUSION:: Significant challenges remain to standardisation of
      imaging practice in accordance with national best-practice guidelines. ADVANCES
      IN KNOWLEDGE:: This is the first publication to date evaluating current UK
      imaging practice for assessing myeloma since the publication of new guidelines
      recommending use of advanced cross-sectional imaging techniques. Skeletal survey
      remains the most commonly performed first-line imaging test in patients with
      suspected or confirmed myeloma and this is largely due to resource limitations
      within radiology departments.

PMID- 30102562
TI  - Clinical significance of the post-radiotherapy 18F-fluorodeoxyglucose positron
      emission tomography response in nasopharyngeal cancer.
AB  - OBJECTIVE: The aim of the present study was to evaluate the clinical significance
      of the post-radiotherapy 18F-fluorodeoxyglucose positron emission tomography (18F
      FDG PET) response for detecting residual disease and predicting survival outcome
      in patients with nasopharyngeal cancer. METHODS: We reviewed 143 patients with
      nasopharyngeal cancer who underwent 18F-FDG PET within 6 months after completion
      of radiotherapy between 2001 and 2012. 18F-FDG PET findings at the primary tumor
      (T-) and regional lymph nodes (N-) were separately assessed and considered
      negative [PET (-)] or positive [PET (+)] depending on the remaining focal
      increased uptake of 18F-FDG that was greater than that of the surrounding muscle
      or blood vessels. The standard of reference was histopathological confirmation or
      clinical/imaging follow-up. Overall survival (OS), distant metastasis-free
      survival (DMFS), and locoregional recurrence-free survival (LRRFS) rates were
      estimated from the date of the start of radiotherapy. RESULTS: The median follow
      up period was 73 months (range, 9-182 months). Overall, 83 and 66% of patients
      achieved T-PET (-) and N-PET (-) responses, and the negative predictive values
      (NPV) for T- and N- were 100 and 99%, respectively. The sensitivity, specificity,
      and positive predictive value were 100%, 84%, and 8% for T-, and 67%, 80%, and 7%
      for N-, respectively. The 5 year OS, DMFS, and LRRFS rates were 83%, 83%, and
      87%, respectively, and patients with N-PET (+) with SUVmax >2.5 showed
      significantly inferior 5 year OS and DMFS rates than patients with N-PET (-) or N
      PET (+) with SUVmax <=2.5 (44% vs 86%, p = 0.004; 36% vs 85%, p < 0.001).
      CONCLUSION: In patients that have received definitive (chemo)radiotherapy for
      nasopharyngeal cancer, 18F-FDG PET within 6 months of completion of treatment has
      a high negative predictive value for predicting residual disease and is
      prognostic for long-term treatment outcomes. Patients with remaining focal
      increased uptake of 18F-FDG at lymph nodes may benefit from more aggressive
      treatments, and further studies are needed to validate the clinical significance
      of post-radiotherapy 18F-FDG PET. Advances in knowledge: We found that Post
      radiotherapy 18F-FDG PET findings have a high negative predictive value for
      detecting residual disease and are a significant prognostic factor for treatment
      outcomes.

PMID- 30102563
TI  - Comparison of panoramic radiography and cone beam CT in the assessment of juxta
      apical radiolucency-an answer to Letter to Editor.

PMID- 30102564
TI  - Improving diagnostic accuracy in clinically ambiguous paediatric appendicitis: a
      retrospective review of ultrasound and pathology findings with focus on the non
      visualised appendix.
AB  - OBJECTIVE: To compare pre-operative ultrasound to histopathological results and
      retrospectively assess the diagnostic accuracy of ultrasound in paediatric
      appendicitis. METHODS: 5 year review of all appendectomies performed in patients
      <16 years old in a tertiary referral university hospital. 983 patients had an
      appendicectomy over the time period while 189 patients had a preoperative
      ultrasound. We retrospectively reviewed all of the preoperative imaging in
      conjunction with the reports for the 189 patients; our aim was to determine the
      sensitivity of preoperative ultrasound for the diagnosis of acute appendicitis.
      RESULTS: Of the 189 patients who had an ultrasound, 102 had histology positive
      for appendicitis and 87 had normal histology. Sensitivity overall was 72.55% [95%
      confidence interval (CI) 62.82 to 80.92] and specificity was 77.01% (95% CI 66.75
      to 85.36). A suggested ultrasound diagnosis of appendicitis made positive
      pathology three times more likely and a normal ultrasound made positive pathology
      three times less likely [positive-predictive value 3.16 (95% CI 2.11 to 4.72)
      negative predictive value 0.36 (95% CI 0.25 to 0.50)]. 77% (67/87) of the
      patients whose pathology was ultimately normal had an ultrasound which was either
      normal or suggested an alternative diagnosis. However, in the 33 (17%) of
      patients with a non-visualised appendix, no secondary signs of inflammation or
      alternative diagnosis 16 (48%) had pathologically confirmed appendicitis.
      CONCLUSION: Ultrasound has the potential to improve diagnostic accuracy in
      clinically ambiguous appendicitis. Advances in knowledge: This paper furthers the
      evidence on the efficacy of ultrasound as a diagnostic tool in acute appendicitis
      in children, especially when the diagnosis is clinically equivocal. It also sheds
      further light on the "non-visualized appendix" with almost half of these patients
      having pathologically confirmed appendicitis; meaning advanced imaging with CT or
      MR may be indicated in this cohort.

PMID- 30102565
TI  - Homology Detection Using Multilayer Maximum Clustering Coefficient.
AB  - Homologous sequences are widely used to understand the functions of certain genes
      or proteins. However, there is no consensus to solve the automatic assignment of
      functions to protein problem and many algorithms have different ways of
      identifying homologous clusters in a given set of sequences. In this article, we
      present an algorithm to deal with specific sets, the set of coding sequences
      obtained from phylogenetically close genomes (of the same species, genus, or
      family). When modeled as a graph, these sets have their own characteristics: they
      form more homogeneous and denser clusters. To solve this problem, our algorithm
      makes use of the clustering coefficient, which maximization can lead to the
      expected results from the biological point of view. In addition, we also present
      an algorithm for the identification of sequence domains based on graph topology.
      We also compared our results with those of the TribeMCL tool, a well-established
      algorithm of the area.

PMID- 30102566
TI  - Fixation Differences in Visual Search of Accident Scenes by Novices and Expert
      Emergency Responders.
AB  - OBJECTIVE:: We sought to investigate whether expert-novice differences in visual
      search behavior found in other domains also apply to accident scenes and the
      emergency response domain. BACKGROUND:: Emergency service professionals typically
      arrive at accidents only after being dispatched when a civilian witness has
      called an emergency dispatch number. Differences in visual search behavior
      between the civilian witness (usually a novice in terms of emergency response)
      and the professional first responders (experts at emergency response) could thus
      result in the experts being given insufficient or erroneous information, which
      would lead them to arrive unprepared for the actual situation. METHOD:: A between
      subjects, controlled eye-tracking experiment with 20 novices and 17 experts
      (rescue and ambulance service personnel) was conducted to explore expert-novice
      differences in visual search of accident and control images. RESULTS:: The
      results showed that the experts spent more time looking at task-relevant areas of
      the accident images than novices did, as predicted by the information reduction
      hypothesis. The longer time was due to longer fixation durations rather than a
      larger fixation count. CONCLUSION:: Expert-novice differences in visual search
      are present in the emergency domain. Given that this domain is essential to
      saving lives and also relies heavily on novices as the first link in the chain of
      response, such differences deserve further exploration. APPLICATION:: Visual
      search behavior from experts can be used for training purposes. Eye-tracking
      studies of novices can be used to inform the design of emergency dispatch
      interviews.

PMID- 30102567
TI  - Editorial.

PMID- 30102568
TI  - Loss of HDAC6 alters gut microbiota and worsens obesity.
AB  - Alterations in gut microbiota are known to affect intestinal inflammation and
      obesity. Antibiotic treatment can affect weight gain by elimination of histone
      deacetylase (HDAC) inhibitor-producing microbes, which are anti-inflammatory by
      augmenting regulatory T (Treg) cells. We asked whether mice that lack HDAC6 and
      have potent suppressive Treg cells are protected from microbiota-induced
      accelerated weight gain. We crossed wild-type and HDAC6-deficient mice and
      subjected the offspring to perinatal penicillin, inducing weight gain via
      microbiota disturbance. We observed that male HDAC6-deficient mice were not
      protected and developed profoundly accelerated weight gain. The antibiotic
      exposed HDAC6-deficient mice showed a mixed immune phenotype with increased CD4+
      and CD8+ T-cell activation yet maintained the enhanced Treg cell-suppressive
      function phenotype characteristic of HDAC6-deficient mice. 16S rRNA sequencing of
      mouse fecal samples reveals that their microbiota diverged with time, with HDAC6
      deletion altering microbiome composition. On a high-fat diet, HDAC6-deficient
      mice were depleted in representatives of the S24-7 family and Lactobacillus but
      enriched with Bacteroides and Parabacteroides; these changes are associated with
      obesity. Our findings further our understanding of the influence of HDACs on
      microbiome composition and are important for the development of HDAC6 inhibitors
      in the treatment of human diseases.-Lieber, A. D., Beier, U. H., Xiao, H.,
      Wilkins, B. J., Jiao, J., Li, X. S., Schugar, R. C., Strauch, C. M., Wang, Z.,
      Brown, J. M., Hazen, S. L., Bokulich, N. A., Ruggles, K. V., Akimova, T.,
      Hancock, W. W., Blaser, M. J. Loss of HDAC6 alters gut microbiota and worsens
      obesity.

PMID- 30102569
TI  - Matrix stiffness regulates vascular integrity through focal adhesion kinase
      activity.
AB  - Tumor vasculature is known to be more permeable than the vasculature found in
      healthy tissue, which in turn can lead to a more aggressive tumor phenotype and
      impair drug delivery into tumors. While the stiffening of the stroma surrounding
      solid tumors has been reported to increase vascular permeability, the mechanism
      of this process remains unclear. Here, we utilize an in vitro model of tumor
      stiffening, ex ovo culture, and a mouse model to investigate the molecular
      mechanism by which matrix stiffening alters endothelial barrier function. Our
      data indicate that the increased endothelial permeability caused by heightened
      matrix stiffness can be prevented by pharmaceutical inhibition of focal adhesion
      kinase (FAK) both in vitro and ex ovo. Matrix stiffness-mediated FAK activation
      determines Src localization to cell-cell junctions, which then induces increased
      vascular endothelial cadherin phosphorylation both in vitro and in vivo.
      Endothelial cells in stiff tumors have more activated Src and higher levels of
      phosphorylated vascular endothelial cadherin at adherens junctions compared to
      endothelial cells in more compliant tumors. Altogether, our data indicate that
      matrix stiffness regulates endothelial barrier integrity through FAK activity,
      providing one mechanism by which extracellular matrix stiffness regulates
      endothelial barrier function. Additionally, our work also provides further
      evidence that FAK is a promising potential target for cancer therapy because FAK
      plays a critical role in the regulation of endothelial barrier integrity.-Wang,
      W., Lollis, E. M., Bordeleau, F., Reinhart-King, C. A. Matrix stiffness regulates
      vascular integrity through focal adhesion kinase activity.

PMID- 30102571
TI  - Vessel wall enhancement on MRI in the diagnosis of primary central nervous system
      vasculitis.

PMID- 30102570
TI  - SHP2 protects endothelial cell barrier through suppressing VE-cadherin
      internalization regulated by MET-ARF1.
AB  - Vascular endothelial (VE)-cadherin junctional localization is known to play a
      central role in vascular development, endothelial barrier integrity, and
      homeostasis. The sarcoma (Src) homology (SH) domain containing protein tyrosine
      phosphatase (SHP)2 has been shown to be involved in regulating endothelial
      barrier function; however, the mechanisms remain largely unknown. In this work
      SHP2 knockdown in an HUVEC monolayer increased VE-cadherin internalization and
      endothelial barrier permeability. Loss of SHP2 specifically augmented the GTPase
      activity of ADP-ribosylation factor (ARF)-1. ARF1 knockdown or inhibition of its
      guanine nucleotide exchange factors (GEFs) markedly attenuated VE-cadherin
      internalization and barrier hyperpermeability induced by SHP2 deficiency. SHP2
      knockdown increased the total and phosphorylated levels of MET, whose activity
      was necessary for ARF1 activation and VE-cadherin internalization. Furthermore,
      constitutive endothelium-specific deletion of Shp2 in mice led to disrupted
      endothelial cell junctions, massive hemorrhage, and lethality in embryos. Induced
      and endothelium-specific deletion of Shp2 in adult mice resulted in lung
      hyperpermeability. Inhibitors for ARF1-GEF or MET used in pregnant mice prevented
      the vascular leakage in endothelial Shp2-deleted embryos. Together, our findings
      define a novel role of SHP2 in stabilizing junctional VE-cadherin in the resting
      endothelial barrier through suppressing MET and ARF1 activation.-Zhang, J.,
      Huang, J., Qi, T., Huang, Y., Lu, Y., Zhan, T., Gong, H., Zhu, Z., Shi, Y., Zhou,
      J., Yu, L., Zhang, X., Cheng, H., Ke, Y. SHP2 protects endothelial cell barrier
      through suppressing VE-cadherin internalization regulated by MET-ARF1.

PMID- 30102572
TI  - Sex-Specific Effects of Incubation Temperature on Embryonic Development of Zebra
      Finch (Taeniopygia guttata) Embryos.
AB  - In oviparous species, the embryonic environment-particularly temperature-can
      alter phenotype and survival of an individual by affecting its size as well as
      its metabolic rate. Previous studies have shown that incubation temperatures can
      affect sex ratio in birds; specifically, low incubation temperatures were shown
      to produce a male-biased sex ratio in zebra finches (Taeniopygia guttata)
      possibly because of a higher pre- or postnatal mortality rate in females. We
      hypothesized that sexes respond differently to suboptimal incubation temperature,
      leading to a male-biased sex ratio. To test this hypothesis, zebra finch eggs
      were incubated at 36.1 degrees , 37.5 degrees , or 38.5 degrees C and hatching
      success, hatchling mass, residual yolk mass, and pectoralis mass were measured.
      We found that while hatchling mass was similar between the sexes at 37.5 degrees
      C, female hatchlings were heavier at 36.1 degrees C, and male hatchlings were
      heavier at 38.5 degrees C. Pectoralis muscle mass was similar between the sexes
      at 36.1 degrees C; however, at 37.5 degrees C, female pectoralis mass was heavier
      at hatching than that of males. Females at 37.5 degrees C also had lower residual
      yolk at hatching compared with males, reflecting a higher use of energy by female
      embryos compared with male embryos at this temperature. In contrast, residual
      yolk was similar between the sexes at 36.1 degrees  and 38.5 degrees C. Our
      results suggest that there are sex differences in how incubation temperature
      alters organ mass and yolk energy reserve; this can lead to a difference in
      survival at different incubation temperatures between the sexes. Taken together
      with previous studies showing that females alter incubation behavior with ambient
      temperature, rising ambient temperatures could impact phenotype and survival of
      avian offspring in a sex-specific manner.

PMID- 30102573
TI  - Seven Haircuts.

PMID- 30102574
TI  - A scoping review of research to assess the frequency, types, and reasons for end
      of-life care setting transitions.
AB  - AIMS: Most people approaching the end of life develop care needs, which typically
      change over time. Moves between care settings may be required as health
      deteriorates. However, in some cases, care setting transitions may have little to
      do with end-of-life care needs and instead reflect the needs, demands,
      availability, or funding provisions of the country or funding body and
      organizations providing care. This paper is a scoping review of the international
      peer-reviewed research literature to gain evidence on the frequency and types of
      end-of-life care setting transitions, and the reasons for these moves. METHODS:
      All relevant print and open access research articles published in 2000+ were
      sought using the Directory of Open Access Journals and EBSCO Discovery Host.
      RESULTS: A total of 39 research articles were identified and reviewed. However,
      minimal useful evidence was revealed. Most articles focused solely on hospital
      admissions near death, and some focused on nursing home admissions, with other
      moves infrequently studied. CONCLUSIONS: This review demonstrates the need to
      quantify and justify end-of-life care setting transitions as it appears dying
      people are frequently moved, often as death nears. This research is needed to
      distinguish transitions related to end-of-life care needs and those arising from
      pressures on or from care providers and others unrelated to the person's care
      needs.

PMID- 30102575
TI  - Risk Reduction Research Initiative: A National Community-Academic Framework to
      Improve Health and Social Outcomes.

PMID- 30102576
TI  - Pantoea agglomerans as a new etiological agent of a bacterial necrotic disease of
      mango trees.
AB  - Bacterial apical necrosis of mango trees, a disease elicited by Pseudomonas
      syringae pv. syringae, is a primary limiting factor of the mango crop production
      in the Mediterranean region. In this study, a collection of bacterial isolates
      associated with necrotic symptoms in mango trees similar to those produced by
      bacterial apical necrosis disease were isolated over 5 consecutive years in
      orchards from the Canary Islands. The bacterial isolates were characterized and
      identified as Pantoea agglomerans. Pathogenicity tests conducted on onion bulbs
      and mango plants confirmed that P. agglomerans strains isolated from mango trees
      are a new etiological agent of a bacterial necrotic disease in the Canary
      Islands. Pathogenicity plasmids of the pPATH family have been previously reported
      in P. agglomerans. The majority of putatively pathogenic (n=23) and pathogenic
      (n=4) P. agglomerans strains isolated from mango trees harbored 4 plasmids, one
      of which was close in size to the 135 kb pPATH pathogenicity plasmid. The
      analysis of the presence of two major genes in pPATH plasmids (repA and hrpJ) was
      undertaken in P. agglomerans strains isolated from mango trees. The hrpJ gene was
      detected in the 140 kb plasmid of pathogenic P. agglomerans strains isolated from
      mango trees, but it showed differences in nucleotide sequences compared to other
      pathogenic strains. In contrast, the repA gene was not detected in any of the
      putatively pathogenic and pathogenic P. agglomerans strains isolated from mango
      trees. Finally, genetic characterization and phylogenetic analysis using the hrpJ
      gene and the housekeeping genes gyrB and rpoB showed that almost all P.
      agglomerans strains that were putatively pathogenic and pathogenic on mango trees
      clustered together, forming a differentiated phylogroup with respect to the other
      pathogenic P. agglomerans strains described from other hosts.

PMID- 30102577
TI  - First Report of Silver Leaf Caused by Chondrostereum purpureum on Vaccinium
      corymbosum in Oregon.

PMID- 30102578
TI  - Leaf Blight on Curcuma wenyujin Caused by Phoma matteucciicola in China.

PMID- 30102579
TI  - First Report of Curvularia lunata Causing Leaf Spot of Pennisetum hydridum in
      China.

PMID- 30102580
TI  - First Report of Ligustrum Virus A on Syringa reticulata var. mandshurica
      (Oleaceae) with a New Yellow Vein and Malformed Needle-Shaped Leaf Disease in
      China.

PMID- 30102581
TI  - First Report of Dickeya dianthicola in Potatoes in Australia.

PMID- 30102582
TI  - First Report of Tomato Mottle Mosaic Virus in Tomato Crops in China.

PMID- 30102583
TI  - Effects of Diet and Social Housing on Reproductive Success in Adult Zebrafish,
      Danio rerio.
AB  - Zebrafish (Danio rerio) have proven their efficiency as an animal model for
      genetics and development, but their nutrition and housing requirements continue
      to elude researchers. Diet and housing density were predicted to affect weight
      change and reproductive success in 120 days postfertilization (dpf) zebrafish,
      and growth performance of their progeny. Fish were fed one of four diets, each
      utilizing a different primary protein source (fish meal [ZeiglerTM], algae, or
      insect), while being housed 3.3 or 6.6 fish/L for 3 weeks. Clutch size,
      viability, and larval development of their progeny were monitored out to 10 dpf.
      All diets were sent out for proximate nutrient analysis and fatty acid profiles
      to understand how diet compositions affect reproduction. We found that diet and
      housing proximity affected adult fish weight and larvae growth; diets composed of
      higher levels of protein and polyunsaturated fatty acids (specifically
      arachidonic acid [AA] and eicosapentanoic acid) allowed fish to gain weight and
      produce healthy larvae. Fish housed at higher densities produced smaller embryos,
      but larger larvae than those housed at lower densities. These findings imply that
      significant effects of a modified stimulus are exhibited after relatively short
      periods.

PMID- 30102584
TI  - High Melatonin Conditions by Constant Darkness and High Temperature Differently
      Affect Melatonin Receptor mt1 and TREK Channel trek2a in the Brain of Zebrafish.
AB  - Ambient light and temperature affect reproductive function by regulating
      kisspeptin and gonadotrophin-releasing hormone (GnRH) in vertebrates. Melatonin
      and melatonin receptors, as well as the two-pore domain K+ channel-related K+
      (TREK) channels, are affected by light and/or temperature; therefore, these
      molecules could modulate kisspeptin and GnRH against ambient light and
      temperature. In this study, we investigated the effect of light and temperature,
      which affect melatonin levels in gene expression levels of TREK channels,
      kisspeptin, and GnRH. We first investigated the effects of different light and
      temperature conditions on brain melatonin concentrations by ELISA. Fish were
      exposed to either constant darkness, constant light, high temperature (35 degrees
      C), or low temperature (20 degrees C) for 72 h. Brain melatonin levels were
      significantly high under constant darkness and high temperature. We further
      investigated the effects of high brain melatonin levels by constant darkness and
      high temperature on gene expression levels of melatonin receptors (mt1, mt2, and
      mel1c), TREK channels (trek1b, trek2a, and trek2b), gnrh3, and kiss2 in the adult
      zebrafish brain by real-time polymerase chain reaction. Fish were exposed to
      constant darkness or elevated temperatures (35 degrees C) for 72 h. trek2a,
      kiss2, and gnrh3 levels were increased under constant darkness. High temperature
      decreased gene expression levels of mt1, mt2, mel1c, and gnrh3 in the preoptic
      area, whereas other genes remained unchanged. Melatonin receptors, TREK channels,
      gnrh3, and kiss2 responded differently under high melatonin conditions. The
      melatonin receptors and the TREK channels could play roles in the regulation of
      reproduction by environmental cues, especially ambient light and temperature.

PMID- 30102585
TI  - Considering Dogs as Complementary Targets of Chagas Disease Control.
AB  - This review describes the role that dogs play in Latin American countries where
      Chagas disease is endemic. Multiple studies determined the high frequency with
      which canine populations are infected with Trypanosoma cruzi. The infection
      prevalence of dogs is greater than that of humans and the presence of infected
      dogs in households is associated with a higher risk of human infection. Dog
      infectiousness to triatomine vectors is several-fold higher than that of humans,
      thereby underscoring their major role in the domestic transmission of T. cruzi.
      Insecticide spraying of houses is in most cases efficacious but the lack of
      sustainability hinders this vector-focused strategy. Multi-pronged approaches
      have been adopted to improve control measures but dog intervention was never
      included. Experimental evaluation of systemic insecticides or deltamethrin
      impregnated collars suggested that dog intervention leading to triatomine killing
      could curb domestic transmission of T. cruzi. Larger field studies are required
      to determine its applicability and efficacy. However, the implementation of dog
      intervention could complement other control measures currently in place, mostly
      in periods when vector spraying has been interrupted.

PMID- 30102586
TI  - What Are the Challenges and Facilitators for Implementing a 24-Hour Telephone
      Cancer Service in Qatar? A Literature Review.
AB  - OBJECTIVE: To identify the challenges and facilitators for implementing a 24-h
      telephone cancer service. DATA SOURCES: English language articles were retrieved
      from Medline, Cumulative Index of Nursing and Allied Health Literature, and Ovid
      Nursing electronic databases published from 2000 to 2015. STUDY DESIGN: The
      authors performed an integrative literature review. The qualitative and
      quantitative articles were evaluated using the Critical Appraisal Skills Program.
      All mixed-methods articles were evaluated using the Mixed Methods Appraisal Tool.
      Thematic analyses were used to synthesize the findings from the included
      articles. FINDINGS: The literature of this review highlights the complexity of
      the decisions that accompany the consideration of implementing a teleoncology in
      Qatar. The literature review detailed challenges and facilitators for
      implementing 24-h call service for cancer patients. These were grouped as human,
      technology, documentary tools, and organizational domains. The core concept that
      integrates each of these domains is communication. CONCLUSIONS: If the telephone
      triage is to be implemented in National Center for Cancer Care and Research
      (NCCCR), more research is needed about the characteristics of cancer patients in
      Qatar. A more robust understanding of this population will inform decisions about
      the utility of developing a teleoncology service at NCCCR.

PMID- 30102587
TI  - Infection control measures to prevent hospital transmission of candida.
AB  - Invasive candida infections are the most important causes of nosocomial
      infections in intensive care units and in risky groups such as immunosuppressed
      patients. These infections lead to undesirable consequences such as increased
      morbidity and mortality in patients, prolongation of hospital stay, and increased
      hospital costs. In recent years, the incidence of non-albicans Candida spp.'s has
      increased. Unfortunately, some of these species are naturally resistant to first
      line antifungals. In addition, biofilm formation on the central venous catheter
      and invasive devices may cause treatment failure. The age of the patients, co
      morbid diseases, the units where they are treated, the antibiotics and
      antifungals that are used for the treatment, and invasive devices are risk
      factors for invasive candida infections. Some of these risk factors can be
      reduced by the behavior of health-care workers. The most important goal is to
      take precautions before the occurrence of invasive candida infections. Infection
      control measures to prevent hospital transmission of candida are very important.
      Compliance with hand hygiene before and after contact with the patient is the
      most important step to prevent the spreading of Candida spp. Observation of
      maximal barrier precautions during invasive catheterization is another important
      clause of this aim. Avoiding unnecessary invasive devices, antibiotics, and
      parenteral nutrition are also important to reduce the colonization of candida.

PMID- 30102588
TI  - The bias of word choice and the interpretation of laboratory tests.

PMID- 30102589
TI  - Phosphorus in kidney disease: Culprit or bystander?

PMID- 30102590
TI  - Which patients with a parapneumonic effusion need a chest tube?

PMID- 30102592
TI  - Diabetes and pregnancy: Risks and opportunities.
AB  - Diabetes in pregnancy increases the risk of adverse maternal, obstetric, fetal,
      and neonatal outcomes. Internists can reduce these risks by optimizing glycemic
      control before conception and providing effective counseling on strategies to
      reduce the risks associated with pregnancy and diabetes. Routine screening of
      reproductive-age women with diabetes should include a comprehensive physical
      examination and laboratory tests to identify at-risk patients and begin strategic
      management. A review of medications for teratogenic potential is also needed.

PMID- 30102591
TI  - Liver enzymes: No trivial elevations, even if asymptomatic.
AB  - Primary care physicians are at the forefront in screening for abnormal levels of
      liver enzymes and investigating the likely causes by obtaining a detailed history
      and physical examination, followed by appropriate laboratory and diagnostic
      workup. This review outlines common causes for the two main mechanisms of liver
      injury--cholestasis and hepatocellular insult--and explores the associated risk
      factors, methods of diagnosis, and management, with a focus on nonalcoholic fatty
      liver disease, one of the most often encountered causes of abnormal liver enzyme
      levels.

PMID- 30102593
TI  - Phosphorus binders: The new and the old, and how to choose.
AB  - In caring for patients with chronic kidney disease, it is important to prevent
      and treat hyperphosphatemia with a combination of dietary restrictions and
      phosphorus binders. This review describes the pathophysiology and control of
      hyperphosphatemia and the different classes of phosphorus binders with respect to
      their availability, cost, side effects, and scenarios in which one class of
      binder may be more beneficial than another.

PMID- 30102594
TI  - Diagnosing and treating bipolar disorder in primary care.
AB  - Major depression often presents in patients with a history of both depression and
      mania, although patients may not have the insight to report manic symptoms as
      problematic. Distinguishing pure (unipolar) depression from bipolar depression is
      important for prognostic and treatment reasons. Once identified, bipolar
      depression can be adequately and safely treated.

PMID- 30102595
TI  - Angular cheilitis induced by iron deficiency anemia.

PMID- 30102596
TI  - Calcific uremic arteriolopathy.

PMID- 30102597
TI  - Palmoplantar exanthema and liver dysfunction.

PMID- 30102598
TI  - Correction to "Correlated Component Analysis for Enhancing the Performance of
      SSVEP-Based Brain-Computer Interface".
AB  - In the above paper [1], a method has been proposed to use the correlated
      component analysis (CORCA) to learn spatial filters with multiple blocks of
      individual training data for steady-state visual evoked potential (SSVEP)-based
      brain-computer interface (BCI) scenario. In order to evaluate the performance of
      CORCA, the task-related component analysis (TRCA)-based method was used as a
      baseline method [2]. For a fair and convincing comparison, the MATLAB codes on
      the website (https://github.com/mnakanishi/TRCA-SSVEP) for implementing TRCA
      method provided by Dr. Masaki Nakanishi, the first author of [2], were used to
      take the role of the TRCA method. At that time, the proposed CORCA-based method
      outperforms the TRCA-based method [1].

PMID- 30102599
TI  - Construction of Signaling Pathways with RNAi Data and Multiple Reference
      Networks.
AB  - Signaling networks are involved in almost all major diseases such as cancer. As a
      result of this, understanding how signaling networks function is vital for
      finding new treatments for many diseases. Using gene knockdown assays such as RNA
      interference (RNAi) technology, many genes involved in these networks can be
      identified. However, determining the interactions between these genes in the
      signaling networks using only experimental techniques is very challenging, as
      performing extensive experiments is very expensive and sometimes, even
      impractical. Construction of signaling networks from RNAi data using
      computational techniques have been proposed as an alternative way to solve this
      challenging problem. However, the earlier approaches are either not scalable to
      large scale networks, or their accuracy levels are not satisfactory. In this
      study, we integrate RNAi data given on a target network with multiple reference
      signaling networks and phylogenetic trees to construct the topology of the target
      signaling network. In our work, the network construction is considered as finding
      the minimum number of edit operations on given multiple reference networks, in
      which their contributions are weighted by their phylogenetic distances to the
      target network. The edit operations on the reference networks lead to a target
      network that satisfies the RNAi knockdown observations. Here, we propose two new
      reference-based signaling network construction methods that provide optimal
      results and scale well to large-scale signaling networks of hundreds of
      components. We compare the performance of these approaches to the state-of-the
      art reference-based network construction method SiNeC on synthetic, semi
      synthetic, and real datasets. Our analyses show that the proposed methods
      outperform SiNeC method in terms of accuracy. Furthermore, we show that our
      methods function well even if evolutionarily distant reference networks are used.
      Application of our methods to the Apoptosis and Wnt signaling pathways recovers
      the known protein-protein interactions and suggests additional relevant
      interactions that can be tested experimentally.

PMID- 30102600
TI  - An Inference Attack on Genomic Data Using Kinship, Complex Correlations, and
      Phenotype Information.
AB  - Individuals (and their family members) share (partial) genomic data on public
      platforms. However, using special characteristics of genomic data, background
      knowledge that can be obtained from the Web, and family relationship between the
      individuals, it is possible to infer the hidden parts of shared (and unshared)
      genomes. Existing work in this field considers simple correlations in the genome
      (as well as Mendel's law and partial genomes of a victim and his family members).
      In this paper, we improve the existing work on inference attacks on genomic
      privacy. We mainly consider complex correlations in the genome by using an
      observable Markov model and recombination model between the haplotypes. We also
      utilize the phenotype information about the victims. We propose an efficient
      message passing algorithm to consider all aforementioned background information
      for the inference. We show that the proposed framework improves inference with
      significantly less information compared to existing work.

PMID- 30102601
TI  - Bone Lead Levels and Risk of Incident Primary Open-Angle Glaucoma: The VA
      Normative Aging Study.
AB  - BACKGROUND: Oxidative stress may play an important role in the etiology of
      primary open-angle glaucoma (POAG). The association between risk of POAG and lead
      exposure, which is an environmental source of oxidative stress, has not been
      fully investigated yet. OBJECTIVE: Our objective was to determine the association
      between bone lead-a biomarker of cumulative lead dose (tibia lead) or an
      endogenous source of stored lead (patella lead)-and incident POAG. METHODS: We
      examined a prospective cohort of 634 POAG-free men [mean baseline age=66.8 y of
      age (SD=6.7)] from the Normative Aging Study (NAS) who had tibia and patella K X
      ray fluorescence lead measurements between 1 January 1991 and 31 December 1999.
      They also had standard ocular evaluations by NAS optometrists until 31 December
      2014. POAG cases were identified by consistent reports of enlarged or asymmetric
      cup-to-disc ratio together with visual field defect or existence of disc
      hemorrhage. We used Cox proportional hazards regressions to estimate hazard
      ratios (HRs) of incident POAG and adjusted survival curves to examine changes in
      the risk of POAG during follow-up according to bone lead quartiles. RESULTS: We
      identified 44 incident cases of POAG by the end of follow-up (incidence rate=74
      per 10,000 person-years; median follow-up=10.6 y). In fully adjusted models, 10
      fold increases in patella lead and tibia lead were associated with HRs of 5.06
      (95% CI: 1.61, 15.88, p=0.005) and 3.07 (95% CI: 0.94, 10.0, p=0.06),
      respectively. The HRs comparing participants in the third and fourth quartiles
      with the lowest quartile were 3.41 (95% CI: 1.34, 8.66) and 3.24 (95% CI: 1.22,
      8.62) for patella lead (p-for-trend=0.01), and 3.84 (95% CI: 1.54, 9.55) and 2.61
      (95% CI: 0.95, 7.21) for tibia lead (p-for-trend=0.02). CONCLUSIONS: Our study
      provides longitudinal evidence that bone lead may be an important risk factor for
      POAG in the U.S. population. https://doi.org/10.1289/EHP3442.

PMID- 30102603
TI  - Ranking of the most reliable beat morphology and heart rate variability features
      for the detection of atrial fibrillation in short single-lead ECG.
AB  - OBJECTIVE: This study participated in the 2017 PhysioNet/CinC Challenge dedicated
      to the classification of atrial fibrillation (AF), normal sinus rhythm (Normal),
      other arrhythmia (Other) and strong noise, using single-lead electrocardiogram
      (ECG) recordings with a duration  <60 s. The aim is to apply a linear threshold
      based strategy for arrhythmia classification, ranking the most powerful time
      domain ECG features that could be easily reproduced on any platform. APPROACH: An
      algorithm for time domain ECG analysis was designed to extract 44 features with
      focus on the following: noise detection; heart rate variability (HRV) analysis;
      beat morphology analysis and delineation of P-, QRS-, and T-waves in the robust
      average beat; detection of atrial activity by the presence of P-waves in the
      average beat and atrial fibrillatory waves (f-waves) during TQ intervals. A
      linear discriminant analysis (LDA) classifier was optimized on the Challenge
      training set (8528 ECGs) by stepwise selection of a nonredundant feature set
      until maximization of the Challenge F1 score. Heart rate (HR) was an independent
      factor for the LDA classifier design, particular to bradycardia (HR  ?  50 bpm),
      normal rhythm (HR  =  50-100 bpm), tachycardia (HR  ?  100 bpm). MAIN RESULTS:
      The algorithm obtained official Challenge F1 scores of 0.80 (Overall), 0.90
      (Normal), 0.81 (AF), 0.70 (Other), and 0.54 (Noise) on the hidden Challenge test
      set (3658 ECGs). This is equivalent to a true positive rate (TPR)  =  90.1%
      (Normal), 81.5% (AF), 67.7% (Other), and 69.5% (Noise), and a false positive rate
      (FPR)  =  13.6% (Normal), 2.3% (AF), 7.7% (Other), and 1.5% (Noise).
      SIGNIFICANCE: The top five features, which together contributed to about 94% of
      the maximal F1 score were ranked: (1) proportion of RR intervals differing by 
      >50 ms from the preceding RR interval; (2) Poincare plot geometry estimated by
      the ratio of the minor-to-major semi-axes of the fitted ellipse; (3) P-wave
      presence in the average beat; (4) mean percentage of the RR interval first
      differences; and (5) mean correlation of all beats against the average beat. The
      global rank of feature extraction methods highlighted that HRV alone was able to
      provide 92.5% of the maximal F1 score (0.74 versus 0.8). The added value of more
      complex ECG morphology analysis was less significant for Normal, AF, and Other
      rhythms (+0.02 to 0.08 points) than for Noise (+0.19 points); however, these were
      indispensable for wearable ECG recording devices with frequent artefact
      disturbance.

PMID- 30102604
TI  - Perspectives of immunotherapy in isocitrate dehydrogenase-mutant gliomas.
AB  - PURPOSE OF REVIEW: The present review introduces recent progress in eliciting the
      role of mutant isocitrate dehydrogenase (IDH) in gliomas, especially regarding
      its mode of action as a modulator of antitumor immune response, and provides
      rationales for targeting mutant IDH in glioma immunotherapy. Both the development
      of small molecule inhibitors repressing the enzymatic activity of mutant IDH and
      novel, mechanism-led combination immunotherapies are discussed. RECENT FINDINGS:
      Since the discovery of highly frequent IDH mutations in low-grade gliomas and
      nonsolid malignancies, its tumor cell-intrinsic effects have been intensively
      investigated. Tumor cells expressing mutant IDH display profound alterations of
      redox control capacity, phospholipid profile, and ATP supply. Recent findings
      suggest that IDH mutations - via intricate, yet druggable pathways - cause
      immunological alterations, highlighting the importance of oncogenic drivers as
      modulators of antitumor immunity and targets for immunotherapy. SUMMARY: Mutant
      IDH is not only a disease-defining biomarker and oncogenic driver in glioma, but
      is also a neoantigen and a regulator of glioma immune evasion. Effective and
      specific strategies targeting the immunomodulatory properties of mutant IDH may
      complement current (immuno-)therapeutic strategies and approved antiglioma
      treatments to improve outcome.

PMID- 30102602
TI  - Evaluation of Prenatal Exposure to Bisphenol Analogues on Development and Long
      Term Health of the Mammary Gland in Female Mice.
AB  - BACKGROUND: Continued efforts to phase out bisphenol A (BPA) from consumer
      products have been met with the challenges of finding safer alternatives.
      OBJECTIVES: This study aimed to determine whether early-life exposure to BPA and
      its related analogues, bisphenol AF (BPAF) and bisphenol S (BPS), could affect
      female pubertal mammary gland development and long-term mammary health in mice.
      METHODS: Timed pregnant CD-1 mice were exposed to vehicle, BPA (0.5, 5, 50
      mg/kg), BPAF (0.05, 0.5, 5 mg/kg), or BPS (0.05, 0.5, 5 mg/kg) via oral gavage
      between gestation days 10-17. Mammary glands were collected from resulting female
      offspring at postnatal day (PND) 20, 28, 35, and 56, and at 3, 8, and 14 months
      for whole mount, histopathological evaluation, and quantitative real-time
      polymerase chain reaction (qPCR); serum steroid concentrations were also measured
      at these time points. RESULTS: In the bisphenol-exposed mice, accelerated mammary
      gland development was evident during early puberty and persisted into adulthood.
      By late adulthood, mammary glands from bisphenol-exposed female offspring
      exhibited adverse morphology in comparison with controls; most prominent were
      undifferentiated duct ends, significantly more lobuloalveolar hyperplasia and
      perivascular inflammation, and various tumors, including adenocarcinomas. Effects
      were especially prominent in the BPAF 5 mg/kg and BPS 0.5 mg/kg groups. Serum
      steroid concentrations and mammary mRNA levels of Esr1, Pgr, Ar, and Gper1 were
      similar to controls. CONCLUSIONS: These data demonstrate that prenatal exposure
      of mice to BPAF or BPS induced precocious development of the mammary gland, and
      that siblings were significantly more susceptible to spontaneous preneoplastic
      epithelial lesions and inflammation, with an incidence greater than that observed
      in vehicle- and BPA-exposed animals. https://doi.org/10.1289/EHP3189.

PMID- 30102605
TI  - Improved Tumor Purity Metrics in Next-generation Sequencing for Clinical
      Practice: The Integrated Interpretation of Neoplastic Cellularity and Sequencing
      Results (IINCaSe) Approach.
AB  - Neoplastic cellularity contributes to the analytic sensitivity of most present
      technologies for mutation detection, such that they underperform when stroma and
      inflammatory cells dilute a cancer specimen's variant fraction. Thus, tumor
      purity assessment by light microscopy is used to determine sample adequacy before
      sequencing and to interpret the significance of negative results and mutant
      allele fraction afterwards. However, pathologist estimates of tumor purity are
      imprecise and have limited reproducibility. With the advent of massively parallel
      sequencing, large amounts of molecular data can be analyzed by computational
      purity algorithms. We retrospectively compared tumor purity of 3 computational
      algorithms with neoplastic cellularity using hematoxylin and eosin light
      microscopy to determine which was best for clinical evaluation of molecular
      profiling. Data were analyzed from 881 cancer patients from a clinical trial
      cohort, LCCC1108 (UNCseq), whose tumors had targeted massively parallel
      sequencing. Concordance among algorithms was poor, and the specimens analyzed had
      high rates of algorithm failure partially due to variable tumor purity.
      Computational tumor purity estimates did not add value beyond the pathologist's
      estimate of neoplastic cellularity microscopy. To improve present methods, we
      propose a semiquantitative, clinically applicable strategy based on mutant allele
      fraction and copy number changes present within a given specimen, which when
      combined with the morphologic tumor purity estimate, guide the interpretation of
      next-generation sequencing results in cancer patients.This is an open-access
      article distributed under the terms of the Creative Commons Attribution-Non
      Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to
      download and share the work provided it is properly cited. The work cannot be
      changed in any way or used commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 30102606
TI  - Vasa previa: prenatal diagnosis and management.
AB  - PURPOSE OF REVIEW: Vasa previa is a rare disorder of placentation associated with
      a high rate of perinatal morbidity and mortality when undetected before delivery.
      We have evaluated the recent evidence for prenatal diagnosis and management of
      vasa previa. RECENT FINDINGS: Around 85% of cases of vasa previa have one or more
      identifiable risk factors including in-vitro fertilization, multiple gestations,
      bilobed, succenturiate or low-lying placentas, and velamentous cord insertion.
      The development of standardized prenatal targeted scanning protocols may improve
      perinatal outcomes. There is no clear consensus on the optimal surveillance
      strategy including the need for hospitalization, timing of corticosteroids
      administration and the value of transvaginal cervical length measurements.
      Outpatient management is possible if there is no evidence of cervical shortening
      on ultrasound and there are no symptoms of bleeding or uterine contractions.
      Recent national guidelines and expert reviews have recommended scheduled cesarean
      section of all asymptomatic women presenting with vasa previa between 34 and 36
      weeks' gestation. SUMMARY: Prenatal diagnosis of vasa previa is pivotal to
      prevent intrapartum fetal death. Although there is insufficient evidence to
      support the universal mid-gestation ultrasound screening for vasa previa, recent
      evidence indicates the need for standardized prenatal targeted screening
      protocols of pregnancies at high-risk of vasa previa.

PMID- 30102607
TI  - Obesity and abnormal glucose tolerance in the offspring of mothers with diabetes.
AB  - PURPOSE OF REVIEW: Type 2 diabetes and obesity during childhood, puberty, and
      adulthood have become more common. This trend presents a global problem in terms
      of public health and health economics. Associations between intrauterine exposure
      to hyperglycemia, obesity, and abnormal glucose tolerance (AGT) in offspring have
      been reported in populations at high risk of diabetes such as Pima Indians, but
      these associations have not been established in other groups. In this review, we
      summarize the evidence on obesity and AGT in the offspring of mothers with
      diabetes. RECENT FINDINGS: Although there are many reports indicating that the
      incidence of obesity or overweight is higher in the offspring of mothers with
      gestational diabetes, there is no consensus on whether maternal prepregnancy
      obesity has a larger impact than intrauterine exposure to hyperglycemia. While
      the risk of AGT or type 2 diabetes in the offspring of mothers with gestational
      diabetes is thought to increase after puberty, the incidence of AGT is elevated
      by the age of 7 years in the offspring of mothers with untreated gestational
      diabetes. Maternal gestational diabetes is a risk factor for AGT or type 2
      diabetes independent of maternal prepregnancy BMI. When the offspring of women
      who had gestational diabetes and received therapeutic intervention in two
      randomized controlled studies were followed, the prevalence of obesity and
      impaired fasting glucose was lower in some 7-year-old girls, but the effect of
      maternal intervention was limited. The risk of obesity or overweight is higher in
      the offspring of mothers with type 1 diabetes, even after adjustment for maternal
      prepregnancy BMI. The risk of type 2 diabetes in such offspring is also higher.
      Although the offspring of mothers with type 2 diabetes are likely to be at high
      risk for type 2 diabetes, there are only limited reports supporting this
      hypothesis. SUMMARY: Intrauterine exposure to hyperglycemia is associated with
      obesity and AGT among offspring. The present review suggests that these
      associations might depend on the type of maternal diabetes, that is, the timing
      and degree of exposure to hyperglycemia. There are only a small number of studies
      on the effect of therapeutic interventions for maternal diabetes on metabolism in
      the offspring.

PMID- 30102609
TI  - Placement of a Continuous Stellate Ganglion Block for Treatment of Refractory
      Ventricular Fibrillation in the Setting of Known Prinzmetal Angina During
      Pregnancy: A Case Report.
AB  - A patient with a history of Prinzmetal angina, refractory ventricular
      fibrillation, cardiac arrest with an implantable cardioverter-defibrillator, and
      obesity presented to the emergency department at 17 weeks gestational age with a
      chief complaint of angina and multiple episodes of defibrillation. A T3/4
      thoracic epidural was placed to assess the effectiveness of a partial chemical
      sympathectomy in alleviating symptoms of angina as well as decreasing the amount
      of defibrillation episodes. Once this proved to be beneficial in accomplishing
      both of these goals, a more specific approach was designed. A continuous stellate
      ganglion block was then placed controlling both her angina and preventing further
      episodes of defibrillation long enough for her pregnancy to progress beyond 24
      weeks gestational age.

PMID- 30102608
TI  - Multifocal motor neuropathy.
AB  - PURPOSE OF REVIEW: Multifocal motor neuropathy (MMN) has specific clinical and
      electrophysiologic features but can be difficult to diagnose if cases are not
      typical. Intravenous immunoglobulin (IVIg) remains the core initial and long-term
      treatment. In this review, recent advances in the diagnosis, monitoring and
      treatment of MMN are discussed. RECENT FINDINGS: The pathology of MMN likely
      depends on immune-mediated attack of the nodes of Ranvier and paranodal regions
      leading to conduction block. Antiganglioside antibodies are present in over 50%
      of patients. The sensitivity of antibody detection can be improved by testing for
      GM1/galactocerebroside (GM1/GalC) complexes. Complement activation plays a key
      role in the pathophysiology of MMN. Subcutaneous immunoglobulins are an
      efficacious alternative to IVIg for maintenance therapy in MMN. Complement
      inhibitor eculizumab may be a potential future treatment, but further studies are
      necessary. SUMMARY: The European Federation of Neurological Societies
      (EFNS)/Peripheral Nerve Society (PNS) guidelines for the diagnosis of MMN are
      currently widely used but probably need revision. Nerve ultrasound and
      plexus/nerve MRI can be helpful in diagnostic dilemmas. Monitoring of disease and
      response to treatment may improve using disease-specific evaluation scales such
      as MMN-Rasch-built overall disability scale. Further research into the
      pathophysiology of MMN is necessary to direct future treatment strategies.

PMID- 30102610
TI  - Twitter Hashtags for Anesthesiologists: Building Global Communities.
AB  - Twitter is a social media platform that has been encouraged for use among
      anesthesiologists as a way to stimulate conversation, distribute research,
      enhance conference experiences, and expand journal club sessions. We aimed to
      establish the typical baseline use of hashtags that are not related to events
      such as conferences. Systematic searches were performed on Twitter, as well as
      through hashtag-tracking services, to identify actively used anesthesia-related
      hashtags. The most frequently used general anesthesia hashtags were #anesthesia
      and #anaesthesia. The most popular and relevant hashtags within anesthesia
      subspecialties or interest groups include #pedsanes, #anesJC, #OBanes,
      #intubation, #regionalanesthesia, #neuroanesthesia, and #cardiacanesthesia. We
      have identified the most popular anesthesia-related hashtags on Twitter to help
      anesthesiologists increase the reach and degree of discussions in anesthesia
      related social media or twitter verse.

PMID- 30102611
TI  - Postdural Puncture Headache in a Postpartum Female With Previous Spinal Surgery
      Successful Treatment With Caudal Epidural Blood Patch: A Case Report.
AB  - The occurrence of a postdural puncture headache (PDPH) is a known risk associated
      with epidural procedures. The primary nonconservative treatment option for PDPH
      is the performance of an epidural blood patch. This case report describes the use
      of image guidance for placement of a caudal epidural to treat a PDPH in a
      postpartum patient. A caudal catheter was placed under real-time guidance and
      visualization of the deposition of the blood was obtained. By entering via the
      caudal foramen and utilizing a catheter, manipulations in catheter placement
      could be performed to adjust deposition of the blood.

PMID- 30102612
TI  - Adverse effects of proton pump inhibitors: fact or fake news?
AB  - PURPOSE OF REVIEW: The present review summarizes the past year's literature, both
      clinical and basic science, regarding potential adverse effects of proton pump
      inhibitors. RECENT FINDINGS: Proton pump inhibitors are amongst the most widely
      prescribed and overprescribed medications worldwide. Although generally
      considered well tolerated, epidemiologic studies mining large databases have
      reported a panoply of purported serious adverse effects associated with proton
      pump inhibitors, including chronic kidney disease, cognitive decline, myocardial
      infarction, stroke, bone fracture and even death. It should be noted that the
      quality of the evidence underlying these associations is very low and these
      studies, by design, cannot ascribe cause and effect. Nonetheless, these
      associations have been sensationalized in the media and misinterpreted by
      patients and providers. Unintended consequences of the fake news are that
      patients are not being prescribed and/or taking clinical guideline-recommended
      proton pump inhibitors to prevent and treat complications from gastroesophageal
      reflux disease and upper gastrointestinal bleeding precipitated by NSAIDs and
      dual antiplatelet therapies. In addition, physicians, who already have limited
      time to interact with their patients, are spending an inordinate amount of
      additional time placing these findings into proper perspective and reassuring
      their patients when initiating treatment as well as on every follow-up visit.
      SUMMARY: Most of the recent highly publicized serious adverse effects ascribed to
      proton pump inhibitors are not based on demonstrable evidence. Nevertheless, when
      proton pump inhibitors are prescribed long-term, they should be used at the
      lowest effective dose and the need for their use periodically reassessed.

PMID- 30102613
TI  - Editorial: the middle cranial fossa approach.

PMID- 30102614
TI  - Human noroviruses: recent advances in a 50-year history.
AB  - PURPOSE OF REVIEW: Noroviruses are a major cause of gastroenteritis. This review
      summarizes new information on noroviruses that may lead to the development of
      improved measures for limiting their human health impact. RECENT FINDINGS: GII.4
      strains remain the most common human noroviruses causing disease, although GII.2
      and GII.17 strains have recently emerged as dominant strains in some populations.
      Histo-blood group antigen (HBGA) expression on the gut mucosa drives
      susceptibility to different norovirus strains. Antibodies that block virus
      binding to these glycans correlate with protection from infection and illness.
      Immunocompromised patients are significantly impacted by norovirus infection, and
      the increasing availability of molecular diagnostics has improved infection
      recognition. Human noroviruses can be propagated in human intestinal enteroid
      cultures containing enterocytes that are a significant primary target for
      initiating infection. Strain-specific requirements for replication exist with
      bile being essential for some strains. Several vaccine candidates are progressing
      through preclinical and clinical development and studies of potential antiviral
      interventions are underway. SUMMARY: Norovirus epidemiology is complex and
      requires continued surveillance to track the emergence of new strains and
      recombinants, especially with the continued progress in vaccine development.
      Humans are the best model to study disease pathogenesis and prevention. New in
      vitro cultivation methods should lead to better approaches for understanding
      virus-host interactions and ultimately to improved strategies for mitigation of
      human norovirus-associated disease.

PMID- 30102615
TI  - Chronic rejection in vascularized composite allotransplantation.
AB  - PURPOSE OF REVIEW: Vascularized composite allografts (VCA), which restore
      severely damaged body parts that cannot be repaired with conventional surgical
      techniques, often undergo acute skin rejection episodes in the early postgraft
      period. Although the risk of human VCA to be affected by chronic rejection was
      initially unknown, such cases were recently observed. RECENT FINDINGS: Chronic
      rejection targets preferentially the skin (dermal sclerosis, adnexal atrophy,
      necrosis) and vessels (graft vasculopathy) and may cause graft dysfunction, often
      resulting in ischemic graft loss. Both immune (cell-mediated and antibody
      mediated) and nonimmune mechanisms seem to be involved. The early diagnosis and
      management of chronic rejection are challenging. Changes of chronic rejection may
      be seen macroscopically on the skin and can be confirmed with skin and deep
      tissue biopsies. New noninvasive imaging techniques, which allow visualization of
      the allograft vasculature, seem promising for the noninvasive detection of graft
      vasculopathy. SUMMARY: Although some features of chronic rejection of VCA start
      to be known, several important questions remain to be answered, concerning namely
      the proper definition of chronic rejection, precise diagnostic criteria, better
      understanding of triggering factors and pathogenetic mechanisms involved and,
      most importantly, adequate treatment. Ideally, chronic rejection should be
      prevented in the future by efficient tolerance-inducing protocols.

PMID- 30102617
TI  - Highways of the Brain, Traffic of the Mind.

PMID- 30102616
TI  - Liposomal Bupivacaine Infiltration for Knee Arthroplasty: Significant Analgesic
      Benefits or Just a Bunch of Fat?

PMID- 30102618
TI  - Clinical and Histological Characterization of Toxic Keratopathy From
      Depatuxizumab Mafodotin (ABT-414), an Antibody-Drug Conjugate: Retraction.

PMID- 30102619
TI  - ICU-acquired pneumonia: is it time to use this term?

PMID- 30102620
TI  - Nonnutritive Sucking at the Mother's Breast Facilitates Oral Feeding Skills in
      Premature Infants: A Pilot Study.
AB  - BACKGROUND: Premature infants have difficulties in transitioning from gavage to
      breastfeeding. Targeted interventions to support breastfeeding in premature
      infants in the neonatal intensive care unit are scarce. PURPOSE: This pilot study
      evaluates the effectiveness of nonnutritive sucking at the mother's breast in
      premature infants to facilitate breastfeeding performance and exclusive
      breastfeeding. METHODS: The study design constituted a single-blinded randomized
      control trial, with 9 participants randomly allocated into experimental (n = 4)
      and control (n = 5) groups. The intervention, nonnutritive sucking at the
      mother's breast thrice a day for 5 minutes, till nutritive breastfeeding was
      started, was done in addition to standard care, which was nonnutritive sucking on
      a finger during gavage feeds. The control group received only standard care.
      Nonnutritive sucking was assessed using "Stages of Nonnutritive Sucking Scale,"
      and breastfeeding performance was assessed using the "Preterm Infant
      Breastfeeding Behavior Scale" by a blinded assessor unaware of the infants'
      allocation. RESULTS: Five infants in the control arm and 4 in the intervention
      arm completed the study. The infants in the intervention group showed faster
      transition to mature stages of nonnutritive sucking (P = .05) and had longer
      sucking bursts during breastfeeding (P = .06) than those in the control group.
      There was no difference in the rates of exclusive breastfeeding at 6 months in
      the intervention and control groups. IMPLICATIONS FOR PRACTICE: Early initiation
      of nonnutritive sucking at the mother's breast in very preterm infants is a safe
      and effective intervention to facilitate maturation of oral feeding and
      breastfeeding behavior. IMPLICATIONS FOR RESEARCH: Nonnutritive sucking at the
      mother's breast can be explored as an intervention, with a larger sample, to
      facilitate exclusive breastfeeding and to establish intervention fidelity.

PMID- 30102622
TI  - Current status and progress of focal therapy in Asia.
AB  - PURPOSE OF REVIEW: With the increasing incidence of low-to-intermediate risk of
      prostate cancer (PCa) by the introduction of prostate-specific antigen (PSA)
      screening, focal therapy has become one of the promising treatment options in the
      world. In Asia, same movement are occurring using several technologies including
      cryoablation, high-intensity focused ultrasound, brachytherapy and irreversible
      electroporation. However, these are still not common strategies to treat organ
      confined PCa. The purpose of this review is to summarize the most updated
      experience and future direction of focal therapy in Asian countries. RECENT
      FINDINGS: The prevalence and diagnosis of PCa are increasing in Asian countries.
      This increase is related to various factors including the widespread
      implementation of PSA testing and lifestyle changes to more Westernized diets.
      With the increasing detection rate of early stage PCa, overdetection and
      overtreatment are recognized even in Asia. In this setting, accumulating data on
      multiparametric MRI and MRI-targeted biopsy as well as MRI-transrectal ultrasound
      (TRUS) fusion biopsy suggest the potential in improving the detection of
      clinically significant PCa in Asia. Furthermore, targeted focal therapy has
      emerged as a promising treatment strategy aiming for both providing oncological
      outcome and maintaining functional preservation in many Asian countries. SUMMARY:
      At present, focal therapy is not a current standard choice for the treatment of
      localized PCa in Asian countries. However, with the increase of localized PCa and
      patient's preference for less invasive treatment with preservation of organ
      function, focal therapy should become a definite treatment option for localized
      PCa in Asia.

PMID- 30102623
TI  - Focal therapy for prostate cancer: concepts and future directions.
AB  - PURPOSE OF REVIEW: To present a perspective on the current status and future
      directions of focal therapy for prostate cancer (PCa). RECENT FINDINGS: Focal
      therapy for localized PCa is a rapidly evolving field. Various recent concepts -
      the index lesion driving prognosis, the enhanced detection of clinically
      significant PCa using multiparametric MRI and targeted biopsy, improved risk
      stratification using novel blood/tissue biomarkers, the recognition that reducing
      radical treatment-related morbidity (along with reducing pathologic progression)
      is a clinically meaningful end-point - have all led to a growing interest in
      focal therapy. Novel focal therapy modalities are being investigated, mostly in
      phase 1 and 2 studies. Recently, level I prospective randomized data comparing
      partial gland ablation with a standard-of-care treatment became available from
      one study. Recent developments in imaging, including 7-T MRI, functional imaging,
      radiomics and contrast-enhanced ultrasound show early promise. We also discuss
      emerging concepts in patient selection for focal therapy. SUMMARY: PCa focal
      therapy has evolved considerably in the recent few years. Overall, these novel
      focal therapy treatments demonstrate safety and feasibility, low treatment
      related toxicity and acceptable short-term and in some cases medium-term
      oncologic outcomes. As imaging techniques evolve, patient selection, detection of
      clinically significant PCa and noninvasive assessment of therapeutic efficacy
      will be further optimized. The aspirational goal of achieving oncologic control
      while reducing radical treatment-related morbidity will drive further innovation
      in the field.

PMID- 30102624
TI  - Current concept of transurethral resection of bladder cancer: from re
      transurethral resection of bladder cancer to en-bloc resection.
AB  - PURPOSE OF REVIEW: Transurethral resection of bladder cancer (TURB) is the
      critical step in the management of nonmuscle invasive bladder cancer (NMIBC).
      This review presents new improvements in the strategy and technique of TURB as
      well as in technological developments used for tumour visualization and removal.
      RECENT FINDINGS: The goal of TURB is to perform complete resection of NMIBC.
      Tumor visualization during procedure can be improved by enhanced optical
      technologies. Fluorescence-guided photodynamic diagnosis (PDD) and narrow-band
      imaging (NBI) used during TURB can improve tumour detection and potentially
      reduce recurrence rate, their influence on progression, however, remains
      controversial. TURB can be performed using monopolar or bipolar electrocautery
      without significant differences in results or safety. To overcome limitations of
      traditional TURB, the technique of en-bloc resection was introduced to improve
      the quality of tumour removal. In selected cases, an early re-resection (re-TURB)
      within 2-6 weeks after initial procedure is recommended. SUMMARY: TURB is a
      fundamental step in diagnosis and treatment of NMIBC. Urologists should be aware
      of promising innovations including new imaging and surgical techniques and their
      potential benefits. Hopefully, new technologies and performance of TURB bring
      improved outcomes, which can alter the indication criteria for re-TURB.

PMID- 30102625
TI  - Platelet-Rich Plasma Augments Subcision in Atrophic Acne Scars: A Split-Face
      Comparative Study.
AB  - BACKGROUND: Acne has a prevalence of 90% among adolescents. Facial scarring
      affects 75% of patients. Autologous platelet-rich plasma (PRP) is a novel
      treatment option for acne scar management and can be used as an adjuvant to acne
      scar revision procedures. Owing to its remodeling properties, PRP when used as an
      adjuvant reduces the total number of sittings. OBJECTIVE: To compare efficacy of
      autologous PRP and subcision against subcision alone in acne scars. METHODOLOGY:
      It was an experimental analytical study conducted over a period of 2 years. Forty
      patients successfully completed the trial. It was a split-face study in which the
      right side of the face was the study side where autologous PRP was injected into
      each scar after performing subcision. The left side of the face was the control
      side where only subcision was performed. Digital photographs were taken at every
      sitting. Analysis was performed using the Wilcoxon signed-rank test and Mann
      Whitney tests in SPSS software. RESULTS: Platelet-rich plasma and subcision
      showed greater improvement (32.08%) in postacne scars as compared to subcision
      alone (8.33%). Rolling acne scars responded greatest (39.27%) followed by box
      type scars (33.88%). CONCLUSION: Platelet-rich plasma and subcision act
      synergistically to improve the appearance of acne scars.

PMID- 30102621
TI  - Understanding sex differences in the regulation of cancer-induced muscle wasting.
AB  - PURPOSE OF REVIEW: We highlight evidence for sexual dimorphism in preclinical and
      clinical studies investigating the cause and treatment of cancer cachexia. RECENT
      FINDINGS: Cancer cachexia is unintended bodyweight loss occurring with cancer,
      and skeletal muscle wasting is a critical predictor of negative outcomes in the
      cancer patient. Skeletal muscle exhibits sexual dimorphism in fiber type,
      function, and regeneration capacity. Sex differences have been implicated in
      skeletal muscle metabolism, mitochondrial function, immune response to injury,
      and myogenic stem cell regulation. All of these processes have the potential to
      be involved in cancer-induced muscle wasting. Unfortunately, the vast majority of
      published studies examining cancer cachexia in preclinical models or cancer
      patients either have not accounted for sex in their design or have exclusively
      studied males. Preclinical studies have established that ovarian function and
      estradiol can affect skeletal muscle function, metabolism and mass; ovarian
      function has also been implicated in the sensitivity of circulating inflammatory
      cytokines and the progression of cachexia. SUMMARY: Females and males have unique
      characteristics that effect skeletal muscle's microenvironment and intrinsic
      signaling. These differences provide a strong rationale for distinct causes for
      cancer cachexia development and treatment in males and females.

PMID- 30102626
TI  - Laser Depigmentation in Extensive Vitiligo.

PMID- 30102627
TI  - A Pilot Study of the Effectiveness of Lithium Versus Quetiapine Immediate Release
      Monotherapy in Patients With Bipolar Spectrum Disorders.
AB  - OBJECTIVE: The aim of this study was to compare the effectiveness of lithium
      versus quetiapine immediate release (IR) monotherapy in patients with bipolar I,
      II, or subthreshold bipolar disorder at any phase. METHODS: Eligible patients
      were randomized to lithium or quetiapine IR for 16 weeks. The difference in the
      time to discontinuation from study due to "all causes" between lithium and
      quetiapine IR groups and changes from baseline to 8 and 16 weeks in depression,
      mania, anxiety, quality of life (QOL), metabolic profiles, and proinflammatory
      markers were compared. RESULTS: Of the 42 patients randomized to lithium (n = 18)
      and quetiapine IR (n = 24), the median time to discontinuation due to "all
      causes" was 6 weeks (95% confidence interval, 2-12 weeks) in the lithium group
      and 8 weeks (95% confidence interval, 6 weeks to not calculable) in the
      quetiapine IR group. The mean time to discontinuation due to "all causes" was 7.7
      +/- 1.1 weeks for lithium versus 8.4 +/- 0.8 weeks for quetiapine IR (P = 0.54).
      There was no significant difference between lithium and quetiapine IR in changes
      in the severity of depression, mania/hypomania, anxiety, and QOL as a whole or
      only in patients with depressive index episode. The decrease in total cholesterol
      was significantly larger with lithium than with quetiapine IR (P = 0.05) as a
      whole, but not only in patients with depression index episode. There was no other
      significant difference in changes in metabolic panels and inflammatory markers
      between the 2 groups. CONCLUSIONS: The difference in effectiveness between
      lithium and quetiapine IR monotherapy in a real-world bipolar population was
      minimal. Large-sample studies are needed to support or refute this finding.

PMID- 30102628
TI  - How to Treat Hypertension in Venlafaxine-Medicated Patients-Pharmacokinetic
      Considerations in Prescribing Amlodipine and Ramipril.
AB  - BACKGROUND: Amlodipine (AMLO) and ramipril (RAMI) belong to the most prescribed
      drugs in patients with hypertension, a condition also encountered in depression.
      Venlafaxine may worsen hypertension because of noradrenergic properties. Although
      of special clinical relevance, data on pharmacokinetic interactions between AMLO,
      RAMI, and venlafaxine (VEN) are lacking. METHODS: Two TDM databases consisting of
      plasma concentrations of VEN and its active metabolite O-desmethylvenlafaxine
      (ODVEN) were analyzed. We considered a group of patients comedicated with AMLO,
      VAMLO (n = 22); a group comedicated with RAMI, VRAMI (n = 20); and a 4:1 control
      group age matched to the VAMLO group receiving VEN without confounding
      medications, V0 (n = 88). Plasma concentrations of VEN, ODVEN, and active moiety,
      AM (VEN + ODVEN); metabolic ratio (ODVEN/VEN); and dose-adjusted plasma
      concentrations (C/D) were compared using nonparametric tests. RESULTS: Groups did
      not differ in daily VEN dose, age, or sex. The metabolic ratio (ODVEN/VEN) was
      lower in the AMLO group (P = 0.029), whereas the RAMI group showed lower values
      for ODVEN (P = 0.029). All other parameters showed no significant differences.
      CONCLUSIONS: Significantly lower values for the metabolic ratio in the AMLO group
      are unlikely to be explained by cytochrome P450 (CYP) 3A4 and weak CYP2D6
      inhibition by AMLO. Other factors such as differences in CYP2D6 polymorphisms and
      metabolizer status may better explain the findings. Ramipril showed modest
      effects with changes in ODVEN concentrations that did not remain significant
      after dose-adjusted comparisons.

PMID- 30102629
TI  - Incidence of Heart Failure and Cardiomyopathy Following Initiation of Medications
      for Attention-Deficit/Hyperactivity Disorder: A Descriptive Study.
AB  - PURPOSE/BACKGROUND: Stimulant abuse is associated with cardiomyopathy, but
      cardiomyopathy rates with therapeutic use of stimulants for attention
      deficit/hyperactivity disorder (ADHD) are poorly characterized. Labels for
      methylphenidate, amphetamine, and atomoxetine caution against use in patients
      with cardiovascular disease. We sought to assess the incidence of new-onset heart
      failure or cardiomyopathy among initiators of these medications.
      METHODS/PROCEDURES: Using the Sentinel distributed database, we analyzed new
      onset heart failure or cardiomyopathy among initiators of selected ADHD
      medications (amphetamine products including lisdexamfetamine, methylphenidate,
      and atomoxetine), by duration of use (0-90, 91-180, 181-270, 271-365, 366-730,
      and 731-1095 days) and age group (<22, 22-44, 45-64, and >=65 years).
      FINDINGS/RESULTS: In our sample of 2,012,948 initiators of ADHD medications,
      44.6% were female, and 54.1% were younger than 22 years. Heart
      failure/cardiomyopathy rates in the age groups younger than 22 and 22 to 44 years
      old were less than 50 per 10,000 person-years, without clear trends by duration
      of use. The highest rates occurred soon after treatment initiation in the age
      group 65 years or older, with 1 case per 10.5 person-years of follow-up, or 950
      cases per 10,000 person-years, for days 0-90. IMPLICATIONS/CONCLUSIONS: Heart
      failure/cardiomyopathy rates were not higher over 3 years of ADHD medication use
      compared with shorter-term treatment. In older age groups, lower rates later in
      treatment could reflect depletion of patients predisposed to the outcome if they
      develop it soon after starting treatment.

PMID- 30102630
TI  - Antipsychotic Use and the Risk of Initiating Medication for Benign Prostate
      Hyperplasia in Persons With Alzheimer Disease: A Matched Cohort Study.
AB  - BACKGROUND: Antipsychotics (APs) are known to exacerbate symptoms of benign
      prostate hyperplasia (BPH) and may even cause urinary retention. The
      anticholinergic effects of APs and their dopamine D2- and alpha-receptor blockade
      may lead to voiding dysfunction of BPH patients. The objective of our study was
      to investigate whether the use of APs is associated with an increased risk of
      initiating medication for BPH in men with Alzheimer disease (AD). METHODS: Data
      from the nationwide MEDALZ (MEDication use and ALZheimer's disease) cohort,
      including all community-dwelling persons diagnosed with AD in Finland, were
      utilized. Register-based data included medication dispensing, comorbidities, and
      hospital discharge diagnoses. Men who initiated APs (n = 4579) were 1:1 matched
      with men who did not initiate APs (n = 4579), according to time since AD
      diagnoses and age. The risk of starting BPH medication was investigated with Cox
      regression. RESULTS: Among AP users, BPH medication was initiated to 345 persons
      (7.5%). Antipsychotic use was not associated with risk of initiating BPH
      medication (comorbidity-adjusted hazard ratio, 0.92; 95% confidence interval,
      0.74-1.15) compared with no use of APs. In addition, no risk was found when AP
      drug substances were analyzed separately. CONCLUSIONS: Use of APs did not
      increase the risk of initiating medication for BPH in men with AD.

PMID- 30102631
TI  - Gastric Bypass Surgery Reduces De Novo Cases of Type 2 Diabetes to Population
      Levels: A Nationwide Cohort Study From Sweden.
AB  - OBJECTIVE: The aim of this study was to determine long-term changes in
      pharmacological treatment of type 2 diabetes after primary Roux-en-Y gastric
      bypass (RYGB) surgery, in patients with and without pharmacological treatment of
      diabetes preoperatively. SUMMARY OF BACKGROUND DATA: Several studies have shown
      that gastric bypass has good effect on diabetes, at least in the short-term. This
      study is a nationwide cohort study using Swedish registers, with basically no
      patients lost to follow-up during up to 7 years after surgery. METHODS: The
      effect of RYGB on type 2 diabetes drug treatment was evaluated in this nationwide
      matched cohort study. Participants were 22,047 adults with BMI >=30 identified in
      the nationwide Scandinavian Surgical Obesity Registry, who underwent primary RYGB
      between 2007 and 2012. For each individual, up to 10 general population
      comparators were matched on birth year, sex, and place of residence. Prescription
      data were retrieved from the nationwide Swedish Prescribed Drug Register through
      September 2015. Incident use of pharmacological treatment was analyzed using Cox
      regression. RESULTS: Sixty-seven percent of patients with pharmacological
      treatment of type 2 diabetes before surgery were not using diabetes drugs 2 years
      after surgery and 61% of patients were not pharmacologically treated up to 7
      years after surgery. In patients not using diabetes drugs at baseline, there were
      189 new cases of pharmacological treatment of type 2 diabetes in the surgery
      group and 2319 in the matched general population comparators during a median
      follow-up of 4.6 years (incidence: 21.4 vs 27.9 per 10,000 person-years; adjusted
      hazard ratio 0.77, 95% confidence interval 0.67-0.89; P < 0.001). CONCLUSIONS:
      Gastric bypass surgery not only induces remission of pharmacological treatment of
      type 2 diabetes but also protects from new onset of pharmacological diabetes
      treatment. The effect seems to persist in most, but not all, patients over 7
      years of follow-up.

PMID- 30102632
TI  - High Operator and Hospital Volume Are Associated With a Decreased Risk of Death
      and Stroke After Carotid Revascularization: A Systematic Review and Meta
      analysis.
AB  - OBJECTIVE: To examine the association between operator or hospital volume and
      procedural outcomes of carotid revascularization. BACKGROUND: Operator and
      hospital volume have been proposed as determinants of outcome after carotid
      endarterectomy (CEA) or carotid artery stenting (CAS). The magnitude and clinical
      relevance of this relationship are debated. METHODS: We systematically searched
      PubMed and EMBASE until August 21, 2017. The primary outcome was procedural (30
      days, in-hospital, or perioperative) death or stroke. Obtained or estimated risk
      estimates were pooled with a generic inverse variance random-effects model.
      RESULTS: We included 87 studies. A decreased risk of death or stroke following
      CEA was found for high compared to low operator volume with a pooled adjusted
      odds ratio (OR) of 0.50 (95% confidence interval [CI] 0.28-0.87; 3 cohorts), and
      a pooled unadjusted relative risk (RR) of 0.59 (95% CI 0.42-0.83; 9 cohorts); for
      high compared to low hospital volume with a pooled adjusted OR of 0.62 (95% CI
      0.42-0.90; 5 cohorts), and a pooled unadjusted RR of 0.68 (95% CI 0.51-0.92; 9
      cohorts). A decreased risk of death or stroke after CAS was found for high
      compared to low operator volume with an adjusted OR of 0.43 (95% CI 0.20-0.95; 1
      cohort), and an unadjusted RR of 0.50 (95% CI 0.32-0.79; 1 cohort); for high
      compared to low hospital volume with an adjusted OR of 0.46 (95% CI 0.26-0.80; 1
      cohort), and no significant decreased risk in a pooled unadjusted RR of 0.72 (95%
      CI 0.49-1.06; 2 cohorts). CONCLUSIONS: We found a decreased risk of procedural
      death and stroke after CEA and CAS for high operator and high hospital volume,
      indicating that aiming for a high volume may help to reduce procedural
      complications. REGISTRATION: This systematic review has been registered in the
      international prospective registry of systematic reviews (PROSPERO):
      CRD42017051491.

PMID- 30102633
TI  - Propensity Score-Matched Analysis Comparing Minimally Invasive Ivor Lewis Versus
      Minimally Invasive Mckeown Esophagectomy.
AB  - INTRODUCTION: Totally minimally invasive esophagectomy (TMIE) is increasingly
      used in treatment of patients with esophageal carcinoma. However, it is currently
      unknown if McKeown TMIE or Ivor Lewis TMIE should be preferred for patients in
      whom both procedures are oncologically feasible. METHODS: The study was performed
      in 4 high-volume Dutch esophageal cancer centers between November 2009 and April
      2017. Prospectively collected data from consecutive patients with esophageal
      cancer localized in the distal esophagus or gastroesophageal junction undergoing
      McKeown TMIE or Ivor Lewis TMIE were included. Patients were propensity score
      matched for age, body mass index, sex, American Society of Anesthesiologists
      classification, Charlson Comorbidity Index, tumor type, tumor location, clinical
      stage, neoadjuvant treatment, and the hospital of surgery. The primary outcome
      parameter was anastomotic leakage requiring reintervention or reoperation.
      Secondary outcome parameters were operation characteristics, pathology results,
      complications, reinterventions, reoperations, length of stay, and mortality.
      RESULTS: Of all 787 included patients, 420 remained after matching. The incidence
      of anastomotic leakage requiring reintervention or reoperation was 23.3% after
      McKeown TMIE versus 12.4% after Ivor Lewis TMIE (P = 0.003). Ivor Lewis TMIE was
      significantly associated with a lower incidence of pulmonary complications (46.7%
      vs 31.9%), recurrent laryngeal nerve palsy (9.5% vs 0.5%), reoperations (18.6% vs
      11.0%), 90-day mortality (7.1% vs 2.9%), shorter median intensive care unit
      length of stay (2 days vs 1 day) and shorter median hospital length of stay (12
      vs 11 days) (all P < 0.05). R0 resection rate was similar between the groups. The
      median number of examined lymph nodes was 21 after McKeown TMIE and 25 after Ivor
      Lewis TMIE (P < 0.001). CONCLUSIONS: Ivor Lewis TMIE is associated with a lower
      incidence of anastomotic leakage, 90-day mortality and other postoperative
      morbidity compared to McKeown TMIE in patients in whom both procedures are
      oncologically feasible.

PMID- 30102634
TI  - Pure Laparoscopic Donor Hepatectomies: Ready for Widespread Adoption?
AB  - OBJECTIVE: In order to minimize the impact of donation, fully laparoscopic donor
      hepatectomy (LDH) is being investigated at a few centers throughout the world. We
      report here our experience with 51 living donor pure laparoscopic hepatectomies.
      BACKGROUND: Adoption of minimal access techniques to living donor liver
      transplantation (LDLT) has been slowed by concerns about donor safety and the
      quality of the grafts. METHODS: Of 344 donor hepatectomies (DHs) for living donor
      liver transplantation (LDLT) since 1998, 51 pure LDH have been performed since
      2009. We report here our experience with 51 living donor pure laparoscopic
      hepatectomy (LH), based on prospectively collected data. There were 31 left
      lateral sectionectomy and 20 full lobectomies LH. We matched full lobe LH to open
      DH prior to introduction of LH. RESULTS: LH increased from 21% of all DH in first
      5 years of performing LH to 45% of DH in the most recent 3 years. Laparoscopic
      donors were more likely female, had lower body mass index, smaller total livers,
      and smaller allografts but longer operating room times. In the total LD
      experience, total 5 donors were converted to open surgery (10%), 2 donors
      required transfusion (4%), and there was 2 donor bile leaks (4%). Recipient
      patient and graft 1-year survival was 98% and 94%. CONCLUSIONS: Our experience
      indicates that LDH for LDLT can be safely used with appropriate attention to
      learning curve and progression from left lateral sectionectomy to right
      hepatectomy.

PMID- 30102635
TI  - Stem Cell Mobilization Is Lifesaving in a Large Animal Preclinical Model of Acute
      Liver Failure.
AB  - INTRODUCTION: Acute liver failure (ALF) affects 2000 Americans each year with no
      treatment options other than liver transplantation. We showed previously that
      mobilization of endogenous stem cells is protective against ALF in rodents. The
      objective of this study was to assess whether stem cell mobilizing drugs are
      lifesaving in a large animal preclinical model of ALF, to assess readiness for a
      clinical trial. METHODS: Male Yorkshire pigs (14-18 kg) were divided into 2
      groups, control (n = 6) and treatment (n = 6). All pigs received an intravenous
      bolus of the hepatotoxin D-galactosamine (0.5 g/kg) via central line and were
      followed up until death or day 28. Treated animals received simultaneous
      intramuscular injection of plerixafor (1 mg/kg) and G-CSF (2 MUg/kg) at baseline,
      24 and 48 hours after toxin infusion to mobilize endogenous stem cells, as
      previously described. Control animals received saline. RESULTS: All control
      animals (6/6) succumbed to liver failure within 91 hours, confirmed by clinical,
      biochemical, and histopathological evidence of ALF. In the treatment group (5/6)
      animals survived indefinitely despite comparable biochemical changes during the
      first 48 hours (P = 0.003). White blood cell count increased by a mean of 4* in
      the treated group at the peak of mobilization (P = 0.0004). CONCLUSIONS: Stem
      cell mobilizing drugs were lifesaving in a preclinical large animal model of ALF.
      Since no therapeutic options other than liver transplantation are currently
      available for critically ill patients with ALF, a multicenter clinical trial is
      warranted.

PMID- 30102636
TI  - A Novel Method for the Prediction of the Pedicle Screw Stability: Regional Bone
      Mineral Density Around the Screw.
AB  - STUDY DESIGN: Prospective feasibility study on consecutive patients. OBJECTIVE:
      The aim of this study was to investigate the ability of regional BMD around the
      pedicle screw to predict the screw fixation. SUMMARY OF BACKGROUND DATA: Pedicle
      screw fixation is the gold standard technique for spinal fusion. Despite the
      advantage of biomechanical stability, screw loosening is a common complication.
      In previous studies, pullout strength and screw insertional torque were
      correlated, and most importantly, affected by bone mineral density (BMD).
      Although the density and structure of the vertebral body are not homogeneous, no
      study has yet evaluated the relationship between screw insertional torque and
      regional BMD around the pedicle screw in vivo. METHODS: Consecutive 50 patients,
      scheduled for transpedicular fixation, were evaluated preoperatively for BMD
      measured by dual-energy absorptiometry (DXA) and quantitative computed tomography
      (QCT). Regional volumetric BMD around the pedicle screw (PS-vBMD) using the novel
      QCT technique was also evaluated. Among all patients, 190 screws (diameter, 7.5
      to 8.5 mm; length, 40 to 45 mm, inserted from L1 to L5) were eligible for this
      study and were analyzed to identify factors contributing to insertional torque.
      The following factors were investigated: age, body mass index, laboratory data,
      pedicle diameter, screw diameter, screw length, and 5 types of bone mineral
      density measures [DXA: spine-areal BMD (aBMD), total hip-aBMD, femoral neck-aBMD,
      QCT: central-vBMD, PS-vBMD]. RESULTS: Insertional torque was significantly
      correlated with each BMD measurement and strongest with PS-vBMD (r=0.61,
      P<0.001). Multiple regression analysis showed PS-vBMD was most strongly
      correlated with screw insertional torque (stdbeta=0.494; P<0.001). A model
      containing the following 5 predictors was significantly associated with screw
      insertional torque: age, pedicle diameter, screw diameter, screw length, and PS
      vBMD. CONCLUSIONS: The preoperative measurement of PS-vBMD was technically
      feasible and reliably predictive of screw insertional torque during
      transpedicular fixation in a clinical setting.

PMID- 30102637
TI  - Twenty-year Longitudinal Follow-up MRI Study of Asymptomatic Volunteers: The
      Impact of Cervical Alignment on Disk Degeneration.
AB  - STUDY DESIGN: A 20-year longitudinal study. OBJECTIVE: To evaluate the long-term
      effect of sagittal alignment of the cervical spine on intervertebral disk
      degeneration in healthy asymptomatic subjects. SUMMARY OF BACKGROUND DATA: This
      study continues a previous 10-year longitudinal study to determine whether
      sagittal alignment affects disk degeneration during normal aging. MATERIALS AND
      METHODS: We assessed 90 healthy subjects (30 men and 60 women) from among 497
      volunteers who underwent magnetic resonance imaging (MRI) and plain radiographs
      of the cervical spine between 1994 and 1996 (follow-up rate 18.1%). The mean age
      at the initial study was 35.5+/-13.4 years (11-65 y). We compared initial MRIs
      and follow-up MRIs, conducted at an average of 21.6 years after the initial
      study, for (1) decreased signal intensity of the intervertebral disks, (2)
      posterior disk protrusion, and (3) disk-space narrowing from C2-3 to C7-T1.
      Subjects were grouped by age at follow-up (under 40 vs. 40 y and older) and by a
      lordotic or nonlordotic cervical sagittal alignment at baseline. We assessed neck
      pain, stiff shoulders, and upper-arm numbness at follow-up, and examined
      associations between clinical symptoms and MRI parameters. RESULTS: Progressive
      changes during the 20-year period included a decrease in disk signal intensity
      (84.4% of subjects), posterior disk protrusion (86.7%), and disk-space narrowing
      (17.8%). No significant association was observed between sagittal alignment and
      decreased disk signal intensity, posterior disk protrusion, or disk-space
      narrowing. Among subjects over the age of 40, progressive degenerative changes at
      C7-T1 were significantly more frequent in nonlordotic subjects (90.9%) compared
      with those with cervical lordosis (54.2%, P=0.032). The prevalence of clinical
      symptoms was similar in lordotic and nonlordotic subjects at follow-up.
      CONCLUSIONS: Nonlordotic cervical alignment was related to the progression of
      disk degeneration at C7-T1 but not other levels. Cervical alignment did not
      affect the development of clinical symptoms in healthy subjects. LEVEL OF
      EVIDENCE: Level III.

PMID- 30102638
TI  - Enterprise Evaluation: A New Opportunity for Public Health Policy.
AB  - Standard evaluation practice in public health remains limited to evaluative
      measures linked to individual projects, even if multiple interrelated projects
      are working toward a common impact. Enterprise evaluation seeks to fill this
      policy gap by focusing on cross-sector coordination and ongoing reflection in
      evaluation. We provide an overview of the enterprise evaluation framework and its
      3 stages: collective creation, individual data collection, and collective
      analysis. We illustrate the application of enterprise evaluation to the Gulf
      Region Health Outreach Program, 4 integrated projects that aimed to strengthen
      health care in Louisiana, Mississippi, Alabama, and the Florida Panhandle after
      the Deepwater Horizon oil spill. Shared commitment to sustainability and strong
      leadership were critical to Gulf Region Health Outreach Program's success in
      enterprise evaluation. Enterprise evaluation provides an important opportunity
      for funding agencies and public health initiatives to evaluate the impact of
      interrelated projects in a more holistic and multiscalar manner than traditional
      siloed approaches to evaluation.This is an open-access article distributed under
      the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
      License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
      provided it is properly cited. The work cannot be changed in any way or used
      commercially without permission from the journal.

PMID- 30102639
TI  - Manipulating the Microcirculation in Sepsis - the Impact of Vasoactive
      Medications on Microcirculatory Blood Flow. A Systematic Review.
AB  - BACKGROUND: Sepsis is life-threatening organ dysfunction due to a dysregulated
      host response to infection. Disturbed microvascular blood flow is associated with
      excess mortality and is a potential future target for interventions. This review
      addresses the evidence for pharmacological manipulation of the microcirculation
      in sepsis assessed by techniques that evaluate the sublingual microvasculature.
      METHODS: Systematic review using a published protocol. Eligibility criteria were
      studies of septic patients published from Jan 2000 - February 2018. Interventions
      were drugs aimed at improving perfusion. Outcome was improvement in microvascular
      flow using OPS, SDF or IDF imaging (GRADE criteria used). RESULTS: 2606 articles
      were screened and 22 included. (6 RCTs, 12 Interventional, 3 Observational, 1
      Pilot, n = 572 participants). Multiple measurement techniques were described,
      including: automated analyses, subjective and composite scoring systems.
      Norepinepherine was not found to improve microvascular flow (low grade evidence,
      n = 6 studies); except in chronic hypertension (low, n = 1 study). Addition of
      arginine vasopressin or terlipressin to norepinepherine maintained flow whilst
      decreasing norepinepherine requirements (high, n = 2 studies). Neither dobutamine
      nor glyceryl trinitrate (GTN) consistently improved flow (low, n = 6 studies). A
      single study (n = 40 participants) demonstrated improved flow with levosimendan
      (high). In a risk of bias assessment 16/16 interventional, pilot and
      observational studies were found to be high risk. CONCLUSIONS: There is no robust
      evidence to date that any one agent can reproducibly lead to improved
      microvascular flow. Furthermore, no study demonstrated outcome benefit of one
      therapeutic agent over another. Updated consensus guidelines could improve
      comparable reporting of measurements and reduce bias, to enable meaningful
      comparisons around the effects of individual pharmacological agents.

PMID- 30102640
TI  - Myocardial Redox Hormesis Protects the Heart of Female Mice in Sepsis.
AB  - Mice challenged with lipopolysaccharide (LPS) develop cardiomyopathy in a sex-
      and redox- dependent fashion. Here we extended these studies to the cecal
      ligation and puncture (CLP) model.We compared male and female FVB mice (wild
      type, WT) and transgenic littermates over-expressing myocardial catalase (CAT).
      CLP induced 100% mortality within 4 days, with similar mortality rates in male
      and female WT and CAT mice. 24 h after CLP, isolated (Langendorff) perfused
      hearts showed depressed contractility in WT male mice, but not in male CAT or
      female WT and CAT mice. In WT male mice, CLP induced a depression of
      cardiomyocyte sarcomere shortening (DeltaSS) and calcium transients (DeltaCai),
      and the inhibition of the sarcoplasmic reticulum Ca ATP-ase (SERCA). These
      deficits were associated with over-expression of NADPH- dependent oxidase 1 (NOX
      1), NOX-2 and cyclooxygenase 2 (COX-2), and were partially prevented in male CAT
      mice. Female WT mice showed unchanged DeltaSS, DeltaCai and SERCA function after
      CLP. At baseline, female WT mice showed partially depressed DeltaSS, DeltaCai and
      SERCA function, as compared to male WT mice, which were associated with NOX-1
      over-expression and were prevented in CAT female mice.In conclusion, in male WT
      mice, septic shock induces myocardial NOX-1, NOX-2 and COX-2, and redox-dependent
      dysregulation of myocardial Ca transporters. Female WT mice are resistant to CLP
      induced cardiomyopathy, despite increased NOX-1 and COX-2 expression, suggesting
      increased antioxidant capacity. Female resistance occurred in association with
      NOX-1 over-expression and signs of increased oxidative signaling at baseline,
      indicating the presence of a protective myocardial redox hormesis mechanism.

PMID- 30102642
TI  - Mental fatigue in central-field and peripheral-field steady-state visually evoked
      potential and its effects on event-related potential responses.
AB  - The steady-state visually evoked potential (SSVEP) is a natural response of the
      brain to visual stimulation at specific frequencies and is used widely for
      electroencephalography-based brain-computer interface (BCI) systems. Although the
      SSVEP is useful for its high level of decoding accuracy, visual fatigue from the
      repetitive visual flickering is an unavoidable problem. In addition, hybrid BCI
      systems that combine the SSVEP with the event-related potential (ERP) have been
      proposed recently. These hybrid BCI systems would improve the decoding accuracy;
      however, the competing effect by simultaneous presentation of the visual stimulus
      could possibly supervene the signal in the hybrid system. Nevertheless, previous
      studies have not sufficiently reported these problems of visual fatigue with
      SSVEP stimuli or the competing effect in the SSVEP+ERP system. In this study, two
      different experiments were designed to explore our claims. The first experiment
      evaluated the visual fatigue level and decoding accuracy for the different types
      of SSVEP stimuli, which were the peripheral-field SSVEP (pSSVEP) and the central
      field SSVEP (cSSVEP). We report that the pSSVEP could reduce the visual fatigue
      level by avoiding direct exposure of the eye-retina to the flickering visual
      stimulus, while also delivering a decoding accuracy comparable to that of cSSVEP.
      The second experiment was designed to examine the competing effect of the SSVEP
      stimuli on ERP performance and vice versa. To do this, the visual stimuli of ERP
      and SSVEP were presented simultaneously as part of the BCI speller layout. We
      found a clear competing effect wherein the evoked brain potentials were
      influenced by the SSVEP stimulus and the band power at the target frequencies was
      also decreased significantly by the ERP stimuli. Nevertheless, these competing
      effects did not lead to a significant loss in decoding accuracy; their features
      preserved sufficient information for discriminating a target class. Our work is
      the first to evaluate the visual fatigue and competing effect together, which
      should be considered when designing BCI applications. Furthermore, our findings
      suggest that the pSSVEP is a viable substitution for the cSSVEP because of its
      ability to reduce the level of visual fatigue while maintaining a minimal loss of
      decoding accuracy.

PMID- 30102643
TI  - TIPS for Preceptors Facilitating Interprofessional Community-Based Clinical
      Experiences.

PMID- 30102641
TI  - Cognitive-behavioral treatment of avoidant/restrictive food intake disorder.
AB  - PURPOSE OF REVIEW: Avoidant/restrictive food intake disorder (ARFID) was added to
      the psychiatric nomenclature in 2013, but little is known about its optimal
      treatment. The purpose of this article is to review the recent literature on
      ARFID treatment and highlight a novel cognitive-behavioral approach, currently
      under study. RECENT FINDINGS: The current evidence base for ARFID treatment
      relies primarily on case reports, case series, and retrospective chart reviews,
      with only a handful of randomized controlled trials in young children. Studies in
      adults are lacking. ARFID treatments recently described in the literature include
      family-based treatment and parent training; cognitive-behavioral approaches;
      hospital-based re-feeding including tube feeding; and adjunctive pharmacotherapy.
      A novel form of outpatient cognitive-behavioral therapy for ARFID (CBT-AR) is one
      treatment currently under study. CBT-AR is appropriate for children, adolescents,
      and adults ages 10 years and more; proceeds through four stages across 20-30
      sessions; and is available in both individual and family-supported versions.
      SUMMARY: There is no evidence-based psychological treatment suitable for all
      forms of ARFID at this time. Several groups are currently evaluating the efficacy
      of new psychological treatments for ARFID - particularly, family-based and
      cognitive-behavioral approaches - but results have not yet been published.

PMID- 30102644
TI  - Emotional Intelligence Relates to NCLEX and Standardized Readiness Test: A Pilot
      Study.
AB  - BACKGROUND: Understanding what factors contribute to NCLEX-RN success is critical
      to nursing programs. Emotional intelligence is one factor that warrants
      investigation. PURPOSE: The purpose of our study was to examine emotional
      intelligence, measured via the Mayer-Salovey-Caruso Emotional Intelligence Test
      2.0, to 2 standardized measures of nursing student performance: the Kaplan
      Nursing Assessment Test (NAT) and NCLEX-RN success. METHODS: A descriptive,
      cohort design with 2 data collections times points (n = 53) evaluated the
      contribution of emotional intelligence to NAT and to NCLEX-RN success, while
      controlling for age. RESULTS: Emotional intelligence global scores were
      significantly related to both NAT and NCLEX-RN. Understanding emotions branch was
      a significant predictor of NAT. Perceiving emotions and understanding emotions
      branches were both significant predictors of NCLEX-RN. CONCLUSIONS: Results
      suggest that enhancing nursing curriculum to include training in perceiving and
      understanding emotions may be beneficial in augmenting student success.

PMID- 30102645
TI  - How Do Hospitalized Adolescents Feel Safe? A Qualitative Study.
AB  - BACKGROUND: The feeling of safety makes an important contribution to the sense of
      well-being and quality of care for hospitalized adolescents, who are at a higher
      risk of feeling unsafe. Feeling unsafe during hospitalization may have a negative
      impact on recovery. Nurses must be sensitive to the possibility that patients
      feel unsafe, even in the absence of obvious direct physical threat. PURPOSE: This
      study explores the experiences of hospitalized adolescents to obtain an
      understanding of psychological safety. METHODS: A qualitative study using
      unstructured interviews was conducted to explore the sense of psychological
      safety of hospitalized adolescents aged 12-18 years and registered in a general
      medical or surgical pediatric unit. Purposive sampling was used to recruit new
      qualified participants until data saturation was reached (N = 16). RESULTS:
      Psychological safety is reflected by the four themes of receiving comprehensive
      support, protection of human dignity, relaxing environment, and attempts to
      adapt. CONCLUSIONS: Hospitalized adolescents stated that healthcare services
      should provide comprehensive support in a relaxing environment that allows them
      to retain their human dignity and that elicits feelings of psychological safety.

PMID- 30102646
TI  - Multiple Cavitary Lung Lesions in an Adolescent: Case Report of a Rare
      Presentation of Nodular Lymphocyte Predominant Hodgkin Lymphoma.
AB  - A 14-year-old male patient presented with a nonproductive cough, weight loss,
      fatigue, and malaise. A chest radiograph showed large bilateral cavitary lung
      lesions in both upper and lower lobes that failed to improve with antibiotics and
      anti-inflammatory medications. Infectious and rheumatologic work-ups were
      negative. Thoracoscopic lung biopsies were diagnostic for nodular lymphocyte
      predominant Hodgkin lymphoma (NLPHL). The patient received combination
      chemotherapy and immunotherapy based on current treatment standards with an
      excellent clinical response. NLPHL is a rare B-cell lymphoma that typically
      presents as peripheral lymph nodal disease, clinically distinct from classical
      Hodgkin lymphoma. The prognosis of NLPHL in children is favorable, although
      relapse rates are high. This case details several unique features of NLPHL and
      describes the presentation, diagnosis, and treatment of an adolescent male with a
      rare pulmonary and cervical NLPHL, the first such case described in a pediatric
      patient.

PMID- 30102647
TI  - National Survey on the Management of Wilms Tumor.
AB  - This study aims to investigate the management of Wilms tumor by the Egyptian
      pediatric surgical association (EPSA) consultants. After approval of the EPSA
      executive board, a questionnaire was distributed individually to all consultants
      attending the general assembly of EPSA 2017 annual congress. Of 88 consultants,
      responses were received from 61. Palpable abdominal mass was indicated by 72.13%
      of respondents as the commonest presenting symptom. Concerning the imaging
      requested, computed tomography was reported by 80.33%. Approximately 62.30% of
      respondents perform 1 to 3 cases annually. Regarding timing of surgery, upfront
      resection was the most frequently reported by 62.30%. A total of 77.05% perform
      lymph node sampling during surgeries. Nephron-sparing surgery was adopted by only
      26.23%, whereas none of the respondents reported the use of minimally invasive
      surgery for management. Overall, 93.44% of surgeons ask for a visit every 3
      months in the first year postoperatively. Upfront nephrectomy is the commonest
      procedure for Wilms tumor in the current practice of EPSA consultants, whereas
      there is consensus against minimally invasive surgery. Surgical guidelines for
      nephron-sparing surgery are still incomplete and need to be tabulated. This study
      urges for a nationwide retrospective analysis to establish a uniform protocol
      with international reference to be adopted in Egypt.

PMID- 30102648
TI  - Postchemotherapy Immunization Practices for Non-HSCT Pediatric Oncology Patients.
AB  - Pediatric oncology patients treated with antineoplastic therapy have impaired
      immune systems that lead to loss of protective antibodies. They require
      reimmunization to protect against vaccine-preventable diseases. There are a
      paucity of studies on the clinical practice of pediatric oncologists and the
      available recommendations are heterogenous. This study describes current
      reimmunization practices among pediatric oncologists. We surveyed the Children's
      Oncology Group (COG)-identified principle investigators to capture clinical
      practices among pediatric oncologists within their institutions regarding
      reimmunization of non-hematopoietic stem cell transplantation patients. The
      majority of respondents did not routinely assess vaccine-related immune status;
      those who did most frequently assessed 6 months after cessation of therapies.
      Methods of assessment included type of therapy received, vaccine titers, and
      absolute lymphocyte counts. Providers from smaller institutions were more likely
      to check vaccine titers than those from larger institutions. More than half of
      the surveyed institutions did not have standardized guidelines available for
      practitioners. There are variations in reimmunization practices among pediatric
      oncologists despite available guidelines on recommended schedules. Further
      research is needed to identify the safest and most cost-effective way to insure
      immunity to infectious disease after the treatment of childhood cancer.

PMID- 30102649
TI  - Bronchoscopy and Bronchoalveolar Lavage in the Diagnosis and Management of
      Pulmonary Infections in Immunocompromised Children.
AB  - BACKGROUND: Immunocompromised children are at high risk of rapid deterioration
      and of developing life-threatening pulmonary infections. Etiologies in this
      setting are diverse, including those that are infectious and noninfectious, and
      many etiologies may coexist. Accurate diagnosis is required for the rational use
      of medications. Fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL)
      can identify infectious causes in this population. OBJECTIVES: The aims of this
      study were to evaluate diagnostic rate, safety, and changes in treatment
      following FOB with BAL, when applied with advanced laboratory diagnostic
      techniques. PATIENTS AND METHODS: We reviewed the records of children who
      underwent FOB with BAL during the period spanning from 2006 to 2014 in the
      Hematology-Oncology Department. BAL samples were processed in microbiology,
      virology, cytology, and molecular laboratories. RESULTS: Antimicrobials were
      initiated in 91 of 117 children. BAL yielded an infectious etiology in 55
      episodes. Management was altered in 74 patients following a positive (40/55) or a
      negative (30/54) result (4 patients had missing data). No severe complications
      associated with the procedures occurred. CONCLUSIONS: Most immunocompromised
      patients with pulmonary manifestations are treated empirically with multiple
      medications. Evaluation FOB/BAL is a useful diagnostic tool, and seems to have
      changed the course of therapy in more than half of patients, by initiation or
      cessation of treatment. FOB/BAL is a safe diagnostic tool for the evaluation of
      pulmonary manifestations in this setting.

PMID- 30102650
TI  - Comparison between self-reported and observed locomotion ability scores in
      patients with stroke: a cross-sectional study.
AB  - This study aimed to investigate (i) the validity of self-reported scores of
      locomotion ability in stroke survivors using the ABILOCO-Benin questionnaire, and
      (ii) the congruence between online Rasch analysis of the ABILOCO-Benin raw scores
      and a conversion table set along with the questionnaire development. Thirty-five
      adult poststroke patients [mean age: 52 (SD: 10) years, 60% men] recruited from
      the rehabilitation department of National University Hospital of Cotonou (Benin),
      self-reported their locomotion ability, filling out the ABILOCO-Benin
      questionnaire [self-reported scores (SRS)]. Afterwards, a physical therapist
      observed and rated the patients' locomotion ability, while they performed each of
      the 15 items of the questionnaire [performance-based scores (PBS)]. Both raw SRS
      and PBS were then converted to linear measures using (i) an online Rasch analysis
      method and (ii) an ordinal-to-interval transformation table. Analyses showed high
      correlation (intraclass correlation coefficient=0.74, P<0.001) and nonsignificant
      difference (P=0.778) between SRS and PBS. Linear measures from online Rasch and a
      conversion table also exhibited high correlation (intraclass correlation
      coefficient=0.92; P<0.001). However, the difference between online analysis and
      the conversion table was significant (P=0.022). In conclusion, self-report is a
      valid method to administer ABILOCO-Benin in stroke patients. The conversion table
      offers a valid opportunity for quick transfer of raw scores to linear measures.
      However, the accuracy of linear measures from the conversion table may be
      slightly affected by missing responses.

PMID- 30102651
TI  - Usefulness of Culturing the Periprosthetic Membrane or Neosynovium for the
      Diagnosis of Infection During Hip and Knee Revision Arthroplasty.
AB  - INTRODUCTION: Identification of microorganisms is critical for correct management
      of an infected arthroplasty. Our hypothesis is that the culture yield depends on
      the location around the prosthesis from which samples are obtained. METHODS: This
      prospective study included 298 revisions of the hip (123) and knee (175). We
      compared the yield of the intraoperative samples obtained, which included
      synovial fluid (two), neosynovium (two), and periprosthetic membrane (two).
      RESULTS: Cultures were positive in 28 cases, in which 15 had the same diagnosis
      considering either the neosynovium or the membrane, and there were 3 cases in
      which the infection could have been diagnosed only by considering the combination
      of both. In all, there were 8 cases in which the infection might have been
      misdiagnosed unless considering a combination of both solid tissue samples (P =
      0.004). CONCLUSIONS: The yields of the periprosthetic membrane and neosynovium do
      not differ significantly, and we recommend considering a combination of both.
      LEVEL OF EVIDENCE: Diagnostic Level II.

PMID- 30102652
TI  - Effect of oral fluconazole 1200 mg/day on QT interval in African adults with HIV
      associated cryptococcal meningitis.
AB  - : We assessed the effect of fluconazole 1200 mg/day on the QT interval in
      cryptococcal meningitis patients. Mean corrected QT (QTc) change from baseline to
      day 7 was 10.1 ms (IQR: -28 to 46 ms) in the fluconazole treatment group and 
      12.6 ms (IQR: -39 to 13.5 ms) in those not taking fluconazole (P = 0.04). No
      significant increase in QTc measurements over 500 ms was observed with
      fluconazole. Nevertheless, it remains important to correct any electrolyte
      imbalance and avoid concomitant drugs that may increase QTc.

PMID- 30102654
TI  - Natural experiment of syphilis treatment with doxycycline or benzathine
      penicillin in HIV-infected patients.
AB  - BACKGROUND: Although doxycycline is widely used as an alternative to benzathine
      penicillin for the treatment of early and late latent syphilis, data on
      serological response following treatment with doxycycline among HIV-infected
      patients are limited. METHODS: In this study, we analysed serological response to
      syphilis treatment with doxycycline among HIV-infected patients treated during a
      benzathine penicillin shortage period and compared with treatment response among
      patients treated with benzathine penicillin. Cases with neurosyphilis and those
      treated with suboptimal doses or with concurrent medications in association with
      benzathine penicillin or doxycycline were excluded. RESULTS: Fifty patients
      treated with doxycycline from September 2014 to December 2016 were compared with
      115 patients treated with benzathine penicillin for early, late latent or latent
      syphilis of unknown duration. Patients treated with doxycycline were slightly
      older [(median 49 years old, 95% confidence interval (95% CI) 43-56] than those
      in the penicillin group (median 44 years old, 95% CI 37-50; P = 0.007). Groups
      had no statistically significant differences regarding sex, HIV suppression under
      treatment and syphilis stages. Serological response to treatment, defined as a
      nonreagent Venereal Disease Research Laboratory (VDRL) or at least a four-fold
      reduction in VDRL titres measured 6-12 months after treatment, was seen in 72%
      (95% CI 58-84) of patients treated with doxycycline and 70% (95% CI 60-78) of
      patients treated with penicillin (P = 0.753). CONCLUSION: We found no
      statistically significant differences in serological response to treatment with
      doxycycline or benzathine penicillin among HIV-infected patients with early, late
      latent or latent syphilis of unknown duration. Our findings suggest that
      doxycycline is an acceptable treatment to HIV-infected patients with nontertiary
      stages of syphilis.

PMID- 30102653
TI  - HIV persistence in mucosal CD4+ T cells within the lungs of adults receiving long
      term suppressive antiretroviral therapy.
AB  - BACKGROUND: The lungs were historically identified as one of the major anatomic
      sites for HIV replication in the pre-antiretroviral therapy (ART) era. However,
      their contribution to HIV persistence in individuals under suppressive ART
      remains understudied. DESIGN: We assessed HIV persistence and comprehensively
      characterized pulmonary mucosal CD4 T cells in HIV-infected (HIV) individuals
      receiving long-term suppressive ART versus uninfected participants. METHODS:
      Bronchoalveolar lavage (BAL), bronchial biopsies, and matched peripheral blood
      were obtained from n = 24 HIV-infected adults receiving long-term suppressive ART
      (median: 9 years) and n = 8 healthy volunteers without respiratory symptoms. HIV
      DNA and cell-associated HIV-RNA were quantified by ultra-sensitive PCR, and lung
      mucosal CD4 T-cell subsets were characterized by multiparameter flow cytometry.
      RESULTS: The levels of HIV-DNA were 13-fold higher in total BAL cells compared to
      blood. Importantly, FACS-sorted CD4 T cells from BAL contained greater levels of
      HIV-DNA compared to peripheral CD4 T cells. BAL CD4 T cells in HIV individuals
      were characterized mostly by an effector memory phenotype, whereas naive and
      terminally differentiated cells were underrepresented compared to blood.
      Furthermore, BAL CD4 T cells expressed higher levels of immune activation (HLA
      DR/CD38) and senescence (CD57) markers. Importantly, BAL was enriched in T-cell
      subsets proposed to be preferential cellular HIV reservoirs, including memory
      CD4CCR6, Th1Th17 (CD4CCR6CCR4CXCR3), CD4CCR6CXCR3CCR4, and CD4CD32a T cells.
      CONCLUSION: The pulmonary mucosa represents an important immunological effector
      site highly enriched in activated and preferential CD4 T-cell subsets for HIV
      persistence during long-term ART in individuals without respiratory symptoms. Our
      findings raise new challenges for the design of novel HIV eradication strategies
      in mucosal tissues.

PMID- 30102655
TI  - Extended cell and plasma drug levels after one dose of a three-in-one
      nanosuspension containing lopinavir, efavirenz, and tenofovir in nonhuman
      primates.
AB  - OBJECTIVE: To characterize a drug-combination nanoparticle (DcNP) containing
      water-insoluble lopinavir (LPV) and efavirenz (EFV), and water-soluble tenofovir
      (TFV), for its potential as a long-acting combination HIV treatment. DESIGN:
      Three HIV drugs (LPV, EFV, TFV) with well established efficacy and safety were
      coformulated into a single DcNP suspension. Two macaques were administered one
      subcutaneous injection and drug concentrations in plasma and mononuclear cells
      (in peripheral blood and lymph nodes) were analyzed over 2 weeks. Pharmacokinetic
      parameters and cell-to-plasma relationships of LPV, EFV, and TFV were determined.
      RESULTS: This three-in-one nanoformulation provided extended concentrations of
      all drugs in lymph node cells that were 57- to 228-fold higher than those in
      plasma. Levels of all three drugs in peripheral blood mononuclear cells persisted
      for 2 weeks at levels equal to or higher than those in plasma. CONCLUSION: With
      long-acting characteristics and higher drug penetration/persistence in cells,
      this three-in-one DcNP may enhance therapeutic efficacy of these well studied HIV
      drugs due to colocalization and targeting of this three-drug combination to HIV
      host cells.

PMID- 30102656
TI  - Metabolic effects of initiating lopinavir/ritonavir-based regimens among young
      children.
AB  - OBJECTIVE: The aim of this study was to estimate the long-term metabolic effects
      of initiating a lopinavir/ritonavir (LPV/r)-based regimen as a first-line therapy
      for HIV-infected children less than 3 years of age in resource-limited settings.
      DESIGN: A prospective cohort study after conclusion of the P1060 randomized
      clinical trials (ClinicalTrials.gov Identifier: NCT00307151), with an overall
      follow-up of 7 years. METHODS: Longitudinal total cholesterol and triglyceride
      measures were compared between 222 and 227 children randomized to initiate LPV/r
      and nevirapine (NVP)-based regimens, respectively. Adipokines (adiponectin and
      leptin) and biomarkers of inflammation [C-reactive protein and interleukin (IL)
      6], microbial translocation (lipopolysaccharide) and immune activation (sCD14),
      measured in 117 participants at a median of 45 weeks of follow-up, were also
      compared by a randomized arm. RESULTS: Mean total cholesterol and the percentage
      of participants with borderline or high total cholesterol was higher in the LPV/r
      arm from years 3 to 7 of follow-up than in the NVP arm (adjusted relative
      differences ranging from 10.9 to 23.4 mg/dl and adjusted relative risks ranging
      from a 60% increased risk to a more than four-fold increased risk for cholesterol
      >=170 mg/dl at 7 years of follow-up). Initiation of a LPV/r-based regimen was not
      associated with high triglycerides over follow-up or large differences in markers
      of metabolic syndrome, inflammation, microbial translocation or immune
      activation. CONCLUSION: Given the virologic superiority of LPV/r-based regimens
      in young children and open questions regarding the roll-out of dolutegravir in
      resource-limited settings, children are currently being maintained on LPV/r-based
      regimens. Our results suggest continual assessment of total cholesterol among
      young children initiating a LPV/r-based regimen to monitor cardiometabolic
      health.

PMID- 30102658
TI  - Accurate quantification of CXCR4-using HIV-1 variants by Illumina deep
      sequencing.
AB  - : Next-generation sequencing is a sensitive method for determining HIV-1 tropism
      but there is a lack of data on the quantification of X4 variants. We evaluated
      MiSeq and 454 GS-Junior platforms for determining HIV-1 tropism and for
      quantifying X4 variants. Both platforms were 93% concordant for determining HIV-1
      tropism and correlated well for determining the proportion of X4 variants
      (Spearman correlation, rho = 0.748; P < 0.0001). MiSeq Illumina sequencing seems
      to be well adapted for characterizing X4-containing samples.

PMID- 30102657
TI  - Carotid artery atherosclerosis is associated with mortality in HIV-positive women
      and men.
AB  - OBJECTIVE: Among people with HIV, there are few long-term studies of noninvasive
      ultrasound-based measurements of the carotid artery predicting major health
      events. We hypothesized that such measurements are associated with 10-year
      mortality in the Women's Interagency HIV Study (WIHS) and Multicenter AIDS Cohort
      Study (MACS), and that associations differ by HIV serostatus. DESIGN: Nested
      cohort study. METHODS: Participants without coronary heart disease underwent B
      mode carotid artery ultrasound, with measurement of common carotid artery intima
      media thickness (IMT); carotid artery plaque (focal IMT > 1.5 mm) at six
      locations; and Young's modulus of elasticity, a measure of arterial stiffness. We
      examined all-cause mortality using Cox models, controlling for demographic,
      behavioral, cardiometabolic, and HIV-related factors. RESULTS: Among 1722 women
      (median age 40 years, 90% nonwhite, 71% HIV-positive) and 1304 men (median age
      50, 39% nonwhite, 62% HIV-positive), 11% died during follow-up. Mortality was
      higher among HIV-positive women [19.9 deaths/1000 person-years, 95% confidence
      interval (CI) 14.7-28.8] than HIV-positive men (15.1/1000, 95% CI 8.3-26.8). In
      adjusted analyses, plaque was associated with mortality (hazard ratio 1.44, 95%
      CI 1.10-1.88) regardless of HIV serostatus, and varied by sex (among women,
      hazard ratio 1.06, 95% CI 0.74-1.52; among men; hazard ratio 2.19, 95% CI 1.41
      3.43). The association of plaque with mortality was more pronounced among HIV
      negative (hazard ratio 3.87, 95% 1.95-7.66) than HIV-positive participants
      (hazard ratio 1.35, 95% CI 1.00-1.84). Arterial stiffness was also associated
      with mortality (hazard ratio 1.43 for highest versus lowest quartile, 95% CI 1.02
      2.01). Greater common carotid artery-IMT was not associated with mortality.
      CONCLUSION: Carotid artery plaque was predictive of mortality, with differences
      observed by sex and HIV serostatus.

PMID- 30102660
TI  - Cardiac status of perinatally HIV-infected children: assessing combination
      antiretroviral regimens in observational studies.
AB  - OBJECTIVE: To evaluate potential adverse associations of individual
      antiretroviral medications used in combination antiretroviral therapy regimens on
      cardiac structure and function in youth with perinatally-acquired HIV infection
      (PHIV). DESIGN: PHIV youth (N = 325) enrolled in a prospective multisite cohort
      study had a single echocardiogram at age 7-16 years to evaluate cardiac function
      and structure. METHODS: We applied several statistical approaches to evaluate
      associations between use of 18 individual antiretroviral medications with Z
      scores for 11 measures of left ventricular function and structure. These included
      simultaneously evaluating all antiretroviral medications in adjusted linear
      regression models controlling for the false discovery rate (FDR), applying
      hierarchical models to estimate individual antiretroviral medication effects as
      deviations from drug class means, and evaluating latent measures of cardiac
      function and structure underlying multiple echocardiographic parameters. RESULTS:
      Youth taking combination regimens with a protease inhibitor (69%) had
      significantly better cardiac function than those on other regimens. After FDR
      control and adjustment for other antiretroviral medications, no individual
      antiretroviral medication was significantly associated with any measure of left
      ventricular function, but zidovudine was associated with higher adjusted mean Z
      scores for one measure of left ventricular structure (end-systolic wall stress).
      Factor analysis identified three latent factors: heart function, heart size, and
      heart wall stress. Lopinavir was associated with better heart function scores,
      whereas zidovudine was associated with higher wall stress scores. Zidovudine and
      nevirapine were associated with higher heart size factor scores. CONCLUSIONS:
      Despite cardioprotective effects of combination regimens in PHIV youth,
      individual antiretroviral medications were associated with altered cardiac
      structure, which could progress to symptomatic cardiomyopathy in adulthood.

PMID- 30102661
TI  - Is HIV patient navigation associated with HIV care continuum outcomes?
AB  - OBJECTIVE: To provide the first systematic review on the associations between HIV
      patient navigation and HIV care continuum outcomes (i.e. linkage to care,
      retention in care, antiretroviral therapy (ART) uptake, medication adherence, and
      viral suppression) in the United States. We identified primary research studies
      that addressed these associations and qualitatively assessed whether provision of
      patient navigation was positively associated with these outcomes, including
      strength of the evidence. METHODS: A systematic review, including both electronic
      [MEDLINE (OVID), EMBASE (OVID), PsycINFO (OVID), and CINAHL (EBSCOhost)] online
      databases and manual searches, was conducted to locate studies published from 1
      January 1996 through 23 April 2018. RESULTS: Twenty studies met our inclusion
      criteria. Of these, 17 found positive associations. Patient navigation was more
      likely to be positively associated with linkage to care (five of six studies that
      assessed this association), retention in care (10 of 11), and viral suppression
      (11 of 15) than with ART uptake (one of four) or ART adherence (two of four).
      However, almost two-thirds of the 17 studies were of weak study quality, and only
      three used a randomized controlled trial design. CONCLUSION: Available evidence
      suggests that patient navigation is a potentially effective strategy to enhance
      engagement in care among persons with HIV. However encouraging, the evidence is
      still weak. Studies with more rigorous methodological designs, and research
      examining characteristics of navigators or navigational programs associated with
      better outcomes, are warranted given the current interest and use of this
      strategy.

PMID- 30102663
TI  - Familial Aggregation of Plastic Surgical Procedures.
AB  - A growing number of patients seeking plastic surgical procedures in the authors'
      practice are first-degree relatives of previous surgical patients. Three
      possibilities for procedural coalescence within a family unit include (1) similar
      morphologic and anatomical patterns within relatives; (2) a captive "audience"
      (family members) appreciates firsthand the surgical result and positive
      difference, be it functional or aesthetic; or (3) the rapport established between
      surgeon and patient leads that patient to recommend his or her surgeon to others.
      The purpose of this study was to identify the authors' recent cohort of family
      members undergoing similar or related procedures performed by the same surgeon
      (D.M.S.), and understand the diagnoses, factors, and rationale for "passing the
      torch" to other family members to undergo surgery. Survey responses from 17
      members of 10 families who sought elective procedures after an index family
      member indicated that both the result of the first operation and rapport with the
      surgeon were important factors in their decision to undergo surgery (mean Likert
      response +/- SD, 4.94 +/- 0.24). Ninety-four percent of family members (16 of 17)
      indicated that the result of the original procedure was the most important factor
      in their decision to undergo subsequent procedures performed by the same surgeon.
      Eighty-eight percent of family members (15 of 17) seeking subsequent procedures
      were not considering undergoing surgery before observing the result of the first
      index procedure. The data demonstrate the importance of achieving an excellent
      surgical result in earning the trust of patients and establishing strong family
      referral patterns.

PMID- 30102664
TI  - Understanding Fatal Fat Embolism in Gluteal Lipoinjection: A Review of the
      Medical Records and Autopsy Reports of 16 Patients.
AB  - BACKGROUND: Deaths secondary to gluteal lipoinjection are relatively recent
      events of major importance. However, little is known in relation to their
      behavior and clinical evolution. Therefore, an analysis was performed of case
      records from clinical cases that encountered this problem, correlating the
      results with the findings during autopsies. METHODS: An analysis was performed of
      records from patients who died secondary to gluteal lipoinjection. Patient
      specific data, surgical procedure, clinical picture, evolution, and outcome were
      analyzed. The findings of the autopsies and the involvement of other organs were
      also analyzed and correlated. RESULTS: From 2000 to 2009, 16 files were obtained
      that fulfilled the indicated requirements. There were no statistically
      significant differences in the general characteristics of the patients, such as
      age, body mass index, or volume lipoinjected or liposuctioned. The clinical
      pictures were similar in all cases, and the autopsy findings showed the presence
      of microembolism in all cases and macroembolism in the most severe cases.
      CONCLUSIONS: The most significant parameter of severity in patients who undergo
      gluteal lipoinjection is the presence of fat in macroscopic form in the
      circulation. The volumes of liposuctioned or lipoinjected fat have little
      influence. Hypoxemia, hypotension, and bradycardia are the characteristic
      clinical features. Although there is no specific treatment, immediate aggressive
      vital support to attempt to stabilize the patient is crucial. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

PMID- 30102659
TI  - p24 revisited: a landscape review of antigen detection for early HIV diagnosis.
AB  - : Despite major advances in HIV testing, early detection of infection at the
      point of care (PoC) remains a key challenge. Although rapid antibody PoC and
      laboratory-based nucleic acid amplification tests dominate the diagnostics
      market, the viral capsid protein p24 is recognized as an alternative early
      virological biomarker of infection. However, the detection of ultra-low levels of
      p24 at the PoC has proven challenging. Here we review the landscape of p24
      diagnostics to identify knowledge gaps and barriers and help shape future
      research agendas. Five hundred and seventy-four research articles to May 2018
      that propose or evaluate diagnostic assays for p24 were identified and reviewed.
      We give a brief history of diagnostic development, and the utility of p24 as a
      biomarker in different populations such as infants, the newly infected, those on
      preexposure prophylaxis and self-testers. We review the performance of commercial
      p24 assays and consider elements such as immune complex disruption, resource-poor
      settings, prevalence, and assay antibodies. Emerging and ultrasensitive assays
      are reviewed and show a number of promising approaches but further translation
      has been limited. We summarize studies on the health economic benefits of using
      antigen testing. Finally, we speculate on the future uses of high-performance p24
      assays, particularly, if available in self-test format.

PMID- 30102662
TI  - Rapid CD4+ T-cell decline is associated with coreceptor switch among MSM
      primarily infected with HIV-1 CRF01_AE in Northeast China.
AB  - OBJECTIVE: CRF01_AE is the most prevalent HIV-1 subtype among MSM in China.
      However, the characteristics and underlying mechanism of the accelerated CD4 T
      cell decline in CRF01_AE-infected MSM remain incompletely understood. DESIGN: A
      long-term prospective follow-up study was conducted with 1388 MSM at risk of HIV
      1 infection in Northeast China. MSM with primary HIV-1 CRF01_AE infection were
      identified and followed for 3-6 years to explore the determinants of rapid CD4 T
      cell decline. METHODS: Tropism was determined in primary infection by both single
      genome amplification-based genotypic prediction using four different algorithms
      and phenotypic determination using clinical isolates. Serial isolates were used
      to determine phenotype of coreceptor switch. Human leukocyte antigen genotypes
      and T-cell activation markers were determined. RESULTS: Fifty-nine MSM primarily
      infected with HIV-1 CRF01_AE were discovered and recruited for the follow-up
      study. CCR5-utilizing (R5) viruses accounted for up to 98% of HIV-1 CRF01_AE
      infections in Northeast China. Survival analysis indicated 39.5% of the patients
      underwent coreceptor switch within 3 years after infection. After adjustment for
      other potential risk factors, linear mixed-effect models demonstrated patients
      experienced R5 to CXCR4-utilizing/dual-tropic (X4/DM) coreceptor switch within 3
      years after infection underwent a faster CD4 T-cell decline compared to those
      without coreceptor switch. CONCLUSIONS: Primary HIV-1 CRF01_AE infection among
      MSM in Northeast China is characterized by R5 viral infection and early R5 to
      X4/DM coreceptor switch, which is associated with rapid CD4 T-cell decline. The
      findings highlight the importance of immediate treatment among the CRF01_AE
      infected MSM.

PMID- 30102665
TI  - The Feasibility Determination of Risky Severe Complications of Arterial
      Vasculature Regarding the Filler Injection Sites at the Tear Trough.
AB  - BACKGROUND: The tear trough is a significant sign of periorbital aging and has
      usually been corrected with filler injection. However, the arterial supply
      surrounding the tear trough could be inadvertently injured during injection;
      therefore, this study aimed to evaluate the nearest arterial locations related to
      the tear trough and investigate the possibility of severe complications following
      filler injection. METHODS: Thirty hemifaces of 15 Thai embalmed cadavers were
      used in this study. RESULTS: The artery located closest to both the inferior
      margin (TT1) and mid-pupil level (TT2) of the tear trough was found to be the
      palpebral branch of the infraorbital artery. Furthermore, at 0.5 mm along the
      tear trough from the medial canthus (TT3), the angular artery was identified,
      which was found to be a branch of the ophthalmic artery. The artery at TT1 and
      TT2 was located beneath both the zygomaticus major and the orbicularis oculi
      muscles. The distances from TT1 to the artery were measured as follows:
      laterally, 2.79 +/- 1.08 mm along the x axis; and inferiorly, 2.88 +/- 1.57 mm
      along the y axis. For the TT2, the artery was located inferomedially from the
      landmark of 4.65 +/- 1.83 mm along the x axis and 7.13 +/- 3.99 mm along the y
      axis. However, the distance along the x axis at TT3 was located medially as 4.00
      +/- 2.37 mm. CONCLUSION: The high risk of injury to the artery at the tear trough
      should be considered because of the numerous arteries to this area.

PMID- 30102666
TI  - Clinical Implications of Gluteal Fat Graft Migration: A Dynamic Anatomical Study.
AB  - BACKGROUND: The intraoperative mortality and overall complication rate for
      gluteal augmentation with fat transplantation is unacceptably high. The current
      controversy among experts regarding safety is whether fat should be placed within
      the gluteus muscle or limited to only the subcutaneous space. The purpose of the
      present study was to test the hypothesis that under certain pressures, fat
      injected within the gluteal muscle can actually migrate out of the muscle and
      into a deeper plane containing critical neurovascular structures, by means of the
      process of deep intramuscular migration. METHODS: A total of eight human cadaver
      dissections were performed. Four hemibuttocks were selected for intramuscular fat
      injection. The patterns of subfascial fat migration were evaluated in three of
      these hemibuttocks by direct visual inspection and in one hemibuttock by
      endoscopic evaluation. Four other hemibuttocks were selected for subcutaneous or
      suprafascial fat injection. RESULTS: Proxy fat was found to migrate through the
      muscle and into the deep submuscular space with each intramuscular injection.
      With subcutaneous injection, no proxy fat was found during dissection in the
      intramuscular septae or submuscular space. CONCLUSIONS: The intramuscular
      insertion of fat, which up to this point has been considered reasonable to
      perform in the superficial muscle and even recommended in the literature, is now
      deemed to be an inexact and risky surgical technique. This technique, because of
      the migratory nature of injected fat, should be avoided from further use in fat
      transplantation to the gluteal region.

PMID- 30102667
TI  - The Impact of Upper Face Botulinum Toxin Injections on Eyebrow Height and
      Forehead Lines: A Randomized Controlled Trial and an Algorithmic Approach to
      Forehead Injection.
AB  - No previous study has objectively evaluated the effect of different forehead
      injection patterns on the eyebrow height and forehead lines. The patients were
      divided into three groups. Botulinum toxin was injected into both the lateral and
      medial eyebrow depressors in all groups. The frontalis was injected using either
      a V-pattern (group 1), a middle horizontal pattern (group 2), or a high
      horizontal pattern (group 3). Objective eyebrow measurements were performed using
      standardized preinjection and postinjection photographs. Validated photonumeric
      scales were used to assess the forehead lines. Fifteen patients (30 eyebrows)
      were included in each group. In all of the groups, 2 weeks after injection, the
      brow was lower at all the measured positions, with the exception of the lateral
      brow edge, which was higher in the three injection patterns. No difference was
      found when comparing group 1 to groups 2 and 3. The middle forehead injection
      pattern lowered the eyebrow more than the upper forehead injection pattern. The
      three techniques improved the forehead lines at rest and with contraction. The
      forehead lines with contraction were more improved in group 1 compared with both
      groups 2 and 3. Each forehead injection pattern yielded different results on
      forehead lines and eyebrow position. Upper forehead injections were less
      effective on forehead lines but prevented eyebrow ptosis. CLINICAL QUESTION/LEVEL
      OF EVIDENCE:: Therapeutic, II.

PMID- 30102668
TI  - Denouement.

PMID- 30102669
TI  - Cerebral Infarction and Refractory Seizures in Zika Virus Infection.

PMID- 30102672
TI  - MRI Characteristics of Spinal Ependymoma in WHO Grade II: A Review of 59 Cases:
      Erratum.

PMID- 30102670
TI  - Searching for Pediatric Legionnaire Disease in a Population With High Adult
      Incidence.

PMID- 30102673
TI  - What's New in SHOCK, September 2018?

PMID- 30102674
TI  - Appropriate Amount of Regular Exercise Is Associated with a Reduced Mortality
      Risk.
AB  - PURPOSE: This study aimed at investigating whether there is a continuous dose
      response relationship between the amount of physical activity (PA) and longevity
      benefit. METHODS: We evaluated the records of 23,257,723 Koreans age >=20 yr who
      had undergone one biennial medical evaluation by the National Health Insurance
      Corporation. Participants with >=20 min of vigorous or >=30 min of moderate PA or
      walking were stratified into four groups: 0 d.wk; 1-3 d.wk; 4 to 5 d.wk; and 6-7
      d.wk. After calculating total metabolic equivalent task-hours per week
      (MET.h.wk), we created eight categories of MET-hours per week (0, 0.1-4.9, 5.0
      9.9, 10.0-14.9, 15.0-19.9, 20.0-24.9, 25.0-29.9, and >=30.0). Multivariate Cox
      proportional hazard analyses were performed. RESULTS: A reverse J-shaped risk
      curve was observed, with the lowest mortality risk in the participants exercising
      4 to 5 d.wk (reference). Participants who did not exercise at all and those who
      exercised with a PA frequency of 1 to 3 d.wk or 6 to 7 d.wk showed a
      significantly increased mortality risk compared with the reference group. When we
      repeated the Cox analysis among the 8 MET.h.wk categories with the participants
      reporting 20.0 to 24.9 MET.h.wk of PA as the reference group, we found that those
      with physical inactivity and 25.0-29.9 or >=30.0 MET.h.wk of PA showed a higher
      mortality risk than the reference group. These relationships were persistently
      observed after adjustment for confounders. CONCLUSIONS: An appropriate amount of
      regular exercise in each specific type of PA was associated with the lowest risk
      of mortality. The inactive participants showed an increased mortality risk, and
      daily PA did not show any additional benefit in the mortality risk.

PMID- 30102675
TI  - Acute High-Intensity Exercise Impairs Skeletal Muscle Respiratory Capacity.
AB  - PURPOSE: The effect of an acute bout of exercise, especially high-intensity
      exercise, on the function of mitochondrial respiratory complexes is not well
      understood, with potential implications for both the healthy population and
      patients undergoing exercise-based rehabilitation. Therefore, this study sought
      to comprehensively examine respiratory flux through the different complexes of
      the electron transport chain in skeletal muscle mitochondria before and
      immediately after high-intensity aerobic exercise. METHODS: Muscle biopsies of
      the vastus lateralis were obtained at baseline and immediately after a 5-km time
      trial performed on a cycle ergometer. Mitochondrial respiratory flux through the
      complexes of the electron transport chain was measured in permeabilized skeletal
      muscle fibers by high-resolution respirometry. RESULTS: Complex I + II state 3
      (state 3CI + CII) respiration, a measure of oxidative phosphorylation capacity,
      was diminished immediately after the exercise (pre, 27 +/- 3 rhom.mg.s; post, 17
      +/- 2 rhom.mg.s; P < 0.05). This decreased oxidative phosphorylation capacity was
      predominantly the consequence of attenuated complex II-driven state 3 (state
      3CII) respiration (pre, 17 +/- 1 rhom.mg.s; post, 9 +/- 2 rhom.mg.s; P < 0.05).
      Although complex I-driven state 3 (3CI) respiration was also lower (pre, 20 +/- 2
      rhom.mg.s; post, 14 +/- 4 rhom.mg.s), this did not reach statistical significance
      (P = 0.27). In contrast, citrate synthase activity, proton leak (state 2
      respiration), and complex IV capacity were not significantly altered immediately
      after the exercise. CONCLUSIONS: These findings reveal that acute high-intensity
      aerobic exercise significantly inhibits skeletal muscle state 3CII and oxidative
      phosphorylation capacity. This, likely transient, mitochondrial defect might
      amplify the exercise-induced development of fatigue and play an important role in
      initiating exercise-induced mitochondrial adaptations.

PMID- 30102676
TI  - Effect of Unintentional Boosting on Exercise Performance in a Tetraplegic
      Athlete.
AB  - Boosting is the induction of autonomic dysreflexia (AD) to reflexively activate
      otherwise dormant thoracolumbar sympathetic circuitry to "boost" the capacity of
      the cardiovascular system and enhance exercise performance. AD is a life
      threatening condition unique to individuals with spinal cord injury (SCI)
      characterized by a sudden increase in sympathetic activity below the level of the
      SCI. Here we report on the temporal HR response to an episode of unintentional
      boosting during a validated field-based exercise performance test in an athlete
      with tetraplegia.An athlete with SCI (C6 motor-complete, sensory-incomplete)
      completed a 20 *20 m repeated sprint field test on two consecutive days. During
      the 13th sprint on day 2, the athlete unintentionally boosted via bladder
      overdistension. Average HR when boosted (i.e., sprints 14-20) was considerably
      higher than before boosting (141 +/- 4 vs 116 +/- 7 bpm) and compared with
      corresponding sprints on day 1 (141 +/- 4 bpm vs 120 +/- 1 bpm). Average time to
      complete 20 m sprints when boosted was also faster than the corresponding sprints
      on day 1 (6.70 +/- 0.05 s vs 6.87 +/- 0.05 s).This case report highlights the
      immediate effect of boosting on HR and field-based exercise performance and
      supports the suggestion that exercise performance in athletes with SCI is limited
      by cardiovascular capacity.

PMID- 30102677
TI  - Leucine Metabolites Do Not Enhance Training-induced Performance or Muscle
      Thickness.
AB  - : Leucine metabolites, alpha-hydroxyisocaproic acid (alpha-HICA) and beta-hydroxy
      beta-methylbutyrate (calcium, HMB-Ca and free acid, HMB-FA), have been proposed
      to augment resistance training-induced changes in body composition and
      performance. PURPOSE: We aimed to conduct a double-blind randomized controlled
      pragmatic trial to evaluate the effects of off-the-shelf leucine metabolite
      supplements of alpha-HICA, HMB-FA and HMB-Ca, on resistance training-induced
      changes in muscle thickness, and performance. METHODS: Forty men were randomly
      assigned to receive alpha-HICA (n=10, fat-free mass [FFM]=62.0 +/- 7.1 kg), HMB
      FA (n=11, FFM=62.7 +/- 10.5 kg), HMB-Ca (n=9, FFM=65.6 +/- 10.1 kg), or placebo
      (PLA; n=10, FFM=64.2 +/- 5.7 kg). The training program consisted of whole body
      thrice weekly resistance training for 8wk (7 exercises/session, 3-4 sets per
      session, at 70-80% 1RM). Skeletal muscle thickness by ultrasound, performance
      measures, and blood measures (creatine kinase [CK], insulin-like growth factor 1
      [IGF-1], growth hormone [GH], cortisol and total testosterone) were evaluated at
      baseline and at the end of weeks 4 and 8. RESULTS: Time-dependent changes were
      observed for muscle thickness (p < 0.001), 1RM bench press and squat (p < 0.001),
      Wingate peak power (p = 0.02), countermovement jump height (p = 0.03), power (p =
      0.006), CK, IGF-1, GH, and cortisol (all p <0.001). No significant between-group
      or time-by-group interactions were observed. CONCLUSION: No leucine metabolite
      resulted in any ergogenic effects on any outcome variable. Supplementation with
      leucine metabolites - alpha-HICA, HMB-FA, or HMB-Ca - is not a supplementation
      strategy that improves muscle growth and strength development in young adult men.

PMID- 30102678
TI  - Blunted Cardiac Output from Overtraining Is Related to Increased Arterial
      Stiffness.
AB  - PURPOSE: Moderate overtraining has been characterized by decreased exercising HR
      and recently decreased exercising stroke volume (SV), independent of alterations
      to blood volume. The aim of this study was to assess changes in arterial
      stiffness and central hemodynamics, and their relationship to exercising SV,
      after 3 wk of overload training. METHODS: Twenty-six cyclists and triathletes
      completed 3 wk of either regular training (CON; n = 13) or overload training (OL;
      n = 13). Testing took place before (PRE) and after regular or overload training
      (POST). Resting measures included brachial blood pressure, HR, carotid-femoral
      pulse wave velocity (PWV) to assess arterial stiffness, and carotid pulse wave
      analysis to assess wave reflections and central hemodynamics. An incremental
      cycle test was used to assess peak power, maximal HR, and maximal lactate to
      assess overtraining status. Cardiac output (Q), SV, and HR were assessed using
      cardiac impedance. RESULTS: Resting arterial stiffness was unaltered in CON but
      increased with OL after increased training (CON -0.1 +/- 0.6 m.s vs OL +0.5 +/-
      0.8 m.s, P = 0.04). Resting blood pressure and central hemodynamics, including
      aortic pressures, augmentation index, and subendocardial viability ratio, did not
      change (all P > 0.05). Maximal SV (CON +3 mL vs OL -9 mL, P = 0.04), HR (CON -2
      +/- 4 bpm vs OL -9 +/- 3 bpm, P < 0.001), and Q (CON +0.32 L.min vs OL -1.75
      L.min, P = 0.01) decreased with OL from PRE to POST. A significant inverse
      relationship existed between changes in PWV and maximal Q (r = -0.44, P = 0.04)
      and changes in PWV and peak power (r = -0.48, P = 0.01), and trended for SV and
      PWV (r = -0.41, P = 0.055). CONCLUSIONS: Overload training results in increased
      resting arterial stiffness and reduced SV during exercise, with no changes to
      resting central hemodynamics.

PMID- 30102680
TI  - Centers for Disease Control and Prevention Syphilis Summit: Difficult Clinical
      and Patient Management Issues.
AB  - Despite over a century of clinical experience in diagnosing and managing patients
      with syphilis, many thorny clinical questions remain unanswered. We focus on
      several areas of uncertainty for the clinician: the role of serologic tests in
      diagnosing syphilis and assessing syphilis treatment responses, and the risk of
      neurosyphilis and ocular syphilis in patients with syphilis. We also address
      whether clinical approaches should differ in patients who are, and are not,
      infected with HIV. The current increases in syphilis rates in the United States
      and elsewhere underscore our urgent need to definitively address these issues.

PMID- 30102681
TI  - Centers for Disease Control and Prevention Syphilis Summit-Diagnostics and
      Laboratory Issues.
AB  - Syphilis, caused by the bacterium Treponema pallidum, is on the rise in the
      United States particularly among men who have sex with men. The disease is
      complex with varied clinical manifestations and challenges remain in the
      laboratory diagnostic setting because T. pallidum is noncultivable and no single
      test can accurately diagnose all stages of the disease. There are missed
      opportunities for the use of direct detection tests in primary and secondary
      syphilis. The increasing use of different reverse sequence algorithms for
      serology testing without validation in populations with varying risks for
      syphilis makes the interpretation of test results difficult; this has led to
      concerns about diagnostic errors or overtreatment. On the other hand, the
      traditional algorithm may miss some early primary syphilis cases, which is of
      concern in high-risk populations. The potential utility of rapid syphilis
      serology tests in different settings or populations remains to be determined. The
      implementation of better tests and appropriate testing algorithms together with
      laboratory guidelines for test use in general will lead to better diagnostic
      options for syphilis.

PMID- 30102679
TI  - Genomewide Association Study of Leisure-Time Exercise Behavior in Japanese
      Adults.
AB  - PURPOSE: Although several genetic factors may play a role in leisure-time
      exercise behavior, there is currently no evidence of a significant genomewide
      association, and candidate gene replication studies have produced inconsistent
      results. METHODS: We conducted a two-stage genomewide association study and
      candidate single-nucleotide polymorphisms (SNP) association study on leisure-time
      exercise behavior using 13,980 discovery samples from the Japan Multi
      Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples
      from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2
      study. Leisure-time physical activity was measured using a self-administered
      questionnaire that inquired about the type, frequency and duration of exercise.
      Participants with >=4 MET.h.wk of leisure-time physical activity were defined as
      exhibiting leisure-time exercise behavior. Association testing using mixed linear
      regression models was performed on the discovery and replication samples, after
      which the results were combined in a meta-analysis. In addition, we tested six
      candidate genetic variants derived from previous genomewide association study.
      RESULTS: We found that one novel SNP (rs10252228) located in the intergenic
      region between NPSR1 and DPY19L1 was significantly associated with leisure-time
      exercise behavior in discovery samples. This association was also significant in
      replication samples (combined P value by meta-analysis = 2.2 * 10). Several SNP
      linked with rs10252228 were significantly associated with gene expression of
      DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous
      system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal
      significance in discovery samples but not in replication samples. CONCLUSIONS: We
      identified a novel genetic variant associated with regular leisure-time exercise
      behavior. Further functional studies are required to validate the role of these
      variants in exercise behavior.

PMID- 30102682
TI  - Syphilis Control in the Postelimination Era: Implications of a New Syphilis
      Control Initiative for Sexually Transmitted Disease/Human Immunodeficiency Virus
      Programs.

PMID- 30102683
TI  - Endothelial Vasodilation After a High-Volume Training Load and Tapered Training
      in Collegiate Female Swimmers.
AB  - Weihl, FM and Van Guilder, GP. Endothelial vasodilation after a high-volume
      training load and tapered training in collegiate female swimmers. J Strength Cond
      Res XX(X): 000-000, 2018-High-volume endurance training loads have been linked to
      adverse remodeling of the heart and large arteries; yet, data on the vascular
      endothelial function are unclear. Moreover, although collegiate-level endurance
      athletes often perform high-volumes of vigorous endurance training and resistance
      training as part of their strength and conditioning programs, it is unknown
      whether they also experience vascular abnormalities, particularly changes in
      endothelial function. The aim of this study was to verify the impact of a high
      volume training load phase followed by low-volume tapered training on endothelial
      vasodilator function in National Collegiate Athletic Association (NCAA) Division
      I competitive female swimmers. Microvascular endothelial vasodilation was
      assessed by pulse arterial tonometry that provides a reactive hyperemia index in
      10 female NCAA Division 1 swimmers after 4 weeks of a high-volume training load,
      and subsequently, after 3 weeks of low-volume tapered training as part of
      preparation for annual conference championships. The reactive hyperemia index was
      calculated as the ratio of the pulse volume amplitude after 5 minutes of left-arm
      brachial artery ischemia to the baseline amplitude, divided by same ratio in the
      contralateral arm. The high-volume training load included a 4-week block of dual
      day sessions (120 minutes per practice) consisting of vigorous intensity
      endurance and high-intensity interval/sprint swim training, coupled with 5K
      running, resistance training, and Olympic weightlifting. Tapered training
      consisted of 3 weeks of 3-5 swims per week at ~50% V[Combining Dot Above]O2max
      for 60 minutes per practice (~4,000 minutes per practice). The reactive hyperemia
      index (1.73 +/- 0.50) was low in athletes after the high-volume training load
      with 8 athletes demonstrating endothelial dysfunction. However, after tapered
      training, the reactive hyperemia index was ~33% higher (2.29 +/- 0.43; 95%
      confidence interval [CI]: 1.98-2.60, p = 0.0223 vs. the high-volume training
      load). Effect size, as expressed by the partial eta (0.46) and Cohen's dz
      (1.1923; 95% CI: 0.1687-2.4643) with tapered training, was large. These results
      demonstrate distinct differences in endothelial vasodilation after 4 weeks of a
      high-volume training load compared with a 3-week taper in NCAA Division I female
      swimmers.

PMID- 30102684
TI  - Differences in the Electromyographic Activity of the Hamstring, Gluteus Maximus,
      and Erector Spinae Muscles in a Variety of Kinetic Changes.
AB  - Hirose, N and Tsuruike, M. Differences in the electromyographic activity of the
      hamstring, gluteus maximus, and erector spinae muscles in a variety of kinetic
      changes. J Strength Cond Res 32(12): 3366-3372, 2018-This study aimed to clarify
      the differences in the electromyographic (EMG) activity of the semitendinosus
      (ST), semimembranosus (SM), biceps femoris long head (BFl), gluteus maximus (GM),
      and erector spinae (ES) muscles during leg curl and bridge exercises across
      different knee angles and isometric contraction outputs. Sixteen male volunteers
      participated in this study. The EMG of all targeted muscles was measured at 20
      and 40% of the maximal voluntary isometric contraction (MVIC) in the leg curl and
      during bilateral and unilateral bridge exercises. The knee flexion angle was
      randomly set at 30, 60, 90, and 120 degrees  during each of the exercises. The
      obtained data were normalized by the MVIC of the corresponding muscle, and each
      of the normalized values was compared with that of the ST. The EMG activity of
      the ST was significantly greater at 120 degrees  of knee flexion than that of 30
      and 60 degrees  of knee flexion during leg curl regardless of intensity (p <
      0.05), in contrast with that of the SM and BFl. However, bridge exercises
      diminished this inverse relationship. The ES activity changed similarly to that
      of the hamstrings, and no difference was observed in the activity of the GM
      regardless of different knee angles during bridge exercise(s). The strength and
      conditioning professionals should alter the knee joint angle and load during
      bridge and leg curl exercises according to which hamstring muscle they want to
      strengthen because ST, SM, and BFl EMG activity varies depending on the intensity
      and knee angles during these exercises.

PMID- 30102685
TI  - Continuous Moderate-Intensity but Not High-Intensity Interval Training Improves
      Immune Function Biomarkers in Healthy Young Men.
AB  - Khammassi, M, Ouerghi, N, Said, M, Feki, M, Khammassi, Y, Pereira, B, Thivel, D,
      and Bouassida, A. Continuous moderate-intensity but not high-intensity interval
      training improves immune function biomarkers in healthy young men. J Strength
      Cond Res XX(X): 000-000, 2018-Effects of endurance running methods on
      hematological profile are still poorly known. This study aimed to compare the
      effects of 2 training regimes; high-intensity interval training (HIIT) and
      moderate-intensity continuous training (MCT) performed at the same external load
      on hematological biomarkers in active young men. Sixteen men aged 18-20 years
      were randomly assigned to HIIT or MCT group. Aerobic capacity and hematological
      biomarkers were assessed before and after 9 weeks of interventions. At baseline,
      aerobic and hematological parameters were similar for the 2 groups. After
      intervention, no significant change was observed in maximal aerobic velocity and
      estimated V[Combining Dot Above]O2max in both groups. Leukocyte (p < 0.01),
      lymphocyte (p < 0.05), neutrophil (p < 0.05), and monocyte (p < 0.01) count
      showed significant improvements in response to the MCT compared with the HIIT
      intervention. The MCT intervention favored an increase in the number of immune
      cells, whereas the opposite occurred as a result of the HIIT intervention. These
      findings suggest that MCT interventions might be superior to HIIT regimes in
      improving immune function in active young men.

PMID- 30102686
TI  - Active Recovery Induces Greater Endurance Adaptations When Performing Sprint
      Interval Training.
AB  - Yamagishi, T and Babraj, J. Active recovery induces greater endurance adaptations
      when performing sprint interval training. J Strength Cond Res XX(X): 000-000,
      2018-This study sought to determine effects of recovery intensity on endurance
      adaptations during sprint interval training (SIT). Fourteen healthy young adults
      (male: 9 and female: 5) were allocated to 1 of 2 training groups: active recovery
      group (ARG, male: 4 and female: 3) or passive recovery group (PRG, male: 5 and
      female: 2). After having completed a 2-week control period, both groups performed
      6 sessions of 4- to 6 30-second sprints interspersed with 4-minute recovery over
      2 weeks. However, only ARG cycled at 40% V[Combining Dot Above]O2peak during the
      4-minute recovery periods, while PRG rested on the bike or cycled unloaded. After
      the 2-week training intervention, both groups improved 10-km time-trial
      performance to a similar extent (ARG: 8.6%, d = 1.60, p = 0.006; PRG: 6.7%, d =
      0.96, p = 0.048) without gains in V[Combining Dot Above]O2peak. However, critical
      power was increased by ARG only (7.9%, d = 1.75, p = 0.015) with a tendency of
      increased maximal incremental power output (5.3%, d = 0.88, p = 0.063). During
      the training, active recovery maintained V[Combining Dot Above]O2 and heart rate
      at a higher level compared with passive recovery (V[Combining Dot Above]O2: p =
      0.005, HR: p = 0.018), suggesting greater cardiorespiratory demands with the
      active recovery. This study demonstrated that greater endurance performance
      adaptations are induced with active recovery when performing SIT over a short
      time frame. The findings of the current study indicate that, with active
      recovery, individuals can gain greater training benefits without increasing total
      training commitment time. Further studies are required to determine whether
      differences are seen with recovery intensity over a longer period.

PMID- 30102687
TI  - Micro-RNA-137 Inhibits Tau Hyperphosphorylation in Alzheimer's Disease and
      Targets the CACNA1C Gene in Transgenic Mice and Human Neuroblastoma SH-SY5Y
      Cells.
AB  - BACKGROUND Alzheimer's disease (AD) results in cognitive impairment. The calcium
      voltage-gated channel subunit alpha-1 C CACNA1C gene encodes an alpha-1 C subunit
      of L-type calcium channel (LTCC). The aim of this study was to investigate the
      role of micro-RNA-137 (miR-137) and the CACNA1C gene in APPswe/PS1DeltaE9
      (APP/PS1) double-transgenic AD mice and in human neuroblastoma SH-SY5Y cells.
      MATERIAL AND METHODS Six-month-old APP/PS1 double-transgenic AD mice (N=6) and
      age-matched normal C57BL/6 mice (N=6) underwent a Morris water maze (MWM) test,
      expression levels of amyloid-beta (Abeta), LTCC, the CACNA1C gene, and miR-137
      were measured in the rat hippocampus and cerebral cortex in both groups of mice.
      A luciferase assay was used to evaluate the effect of miR-137 on the expression
      of CACNA1C in SH-SY5Y human neuroblastoma SH-SY5Y cells. Western blotting was
      used to detect the CACNA1C, phosphorylated-tau (p-tau), and Abeta proteins.
      RESULTS In APP/PS1 transgenic AD mice, spatial learning and memory was
      significantly reduced, levels of Abeta1-40 and Abeta1-42 were increased in the
      serum, hippocampus, and cerebral cortex, expression levels of miR-137 were
      reduced, expression of CACNA1C protein was increased in the hippocampus and
      cerebral cortex, compared with normal control mice. miR-137 regulated the
      expression of the CACNA1C gene. Increased expression levels of p-tau (Ser202,
      Ser396, and Ser404) induced by Abeta1-42 were inhibited by miR-137 mimics in SH
      SY5Y human neuroblastoma cells in vitro. CONCLUSIONS In a transgenic mouse model
      of AD, miR-137 and expression of the CACNA1C gene inhibited the
      hyperphosphorylation of tau protein.

PMID- 30102688
TI  - Provenance and risk in transfer of biological materials.
AB  - Whereas biological materials were once transferred freely, there has been a
      marked shift in the formalisation of exchanges involving these materials,
      primarily through the use of Material Transfer Agreements (MTAs). This paper
      considers how risk aversion dominates MTA negotiations and the impact it may have
      on scientific progress. Risk aversion is often based on unwarranted fears of
      incurring liability through the use of a material or loss of control or missing
      out on commercialisation opportunities. Evidence to date has suggested that
      complexity tends to permeate even straightforward transactions despite extensive
      efforts to implement simple, standard MTAs. We argue that in most cases, MTAs
      need do little more than establish provenance, and any attempt to extend MTAs
      beyond this simple function constitutes stifling behaviour. Drawing on available
      examples of favourable practice, we point to a number of strategies that may
      usefully be employed to reduce risk-averse tendencies, including the promotion of
      simplicity, education of those engaged in the MTA process, and achieving a
      cultural shift in the way in which technology transfer office (TTO) success is
      measured in institutions employing MTAs.

PMID- 30102689
TI  - riboWaltz: Optimization of ribosome P-site positioning in ribosome profiling
      data.
AB  - Ribosome profiling is a powerful technique used to study translation at the
      genome-wide level, generating unique information concerning ribosome positions
      along RNAs. Optimal localization of ribosomes requires the proper identification
      of the ribosome P-site in each ribosome protected fragment, a crucial step to
      determine the trinucleotide periodicity of translating ribosomes, and draw
      correct conclusions concerning where ribosomes are located. To determine the P
      site within ribosome footprints at nucleotide resolution, the precise estimation
      of its offset with respect to the protected fragment is necessary. Here we
      present riboWaltz, an R package for calculation of optimal P-site offsets,
      diagnostic analysis and visual inspection of ribosome profiling data. Compared to
      existing tools, riboWaltz shows improved accuracies for P-site estimation and
      neat ribosome positioning in multiple case studies. riboWaltz was implemented in
      R and is available as an R package at
      https://github.com/LabTranslationalArchitectomics/RiboWaltz.

PMID- 30102691
TI  - Why are RNA virus mutation rates so damn high?
AB  - The high mutation rate of RNA viruses is credited with their evolvability and
      virulence. This Primer, however, discusses recent evidence that this is, in part,
      a byproduct of selection for faster genomic replication.

PMID- 30102690
TI  - Evolutionary diversification of the HAP2 membrane insertion motifs to drive
      gamete fusion across eukaryotes.
AB  - HAPLESS2 (HAP2) is a broadly conserved, gamete-expressed transmembrane protein
      that was shown recently to be structurally homologous to viral class II fusion
      proteins, which initiate fusion with host cells via insertion of fusion loops
      into the host membrane. However, the functional conformation of the HAP2 fusion
      loops has remained unknown, as the reported X-ray structure of Chlamydomonas
      reinhardtii HAP2 lacked this critical region. Here, we report a structure-guided
      alignment that reveals diversification of the proposed HAP2 fusion loops.
      Representative crystal structures show that in flowering plants, HAP2 has a
      single prominent fusion loop projecting an amphipathic helix at its apex, while
      in trypanosomes, three small nonpolar loops of HAP2 are poised to interact with
      the target membrane. A detailed structure-function analysis of the Arabidopsis
      HAP2 amphipathic fusion helix defines key residues that are essential for
      membrane insertion and for gamete fusion. Our study suggests that HAP2 may have
      evolved multiple modes of membrane insertion to accommodate the diversity of
      membrane environments it has encountered during eukaryotic evolution.

PMID- 30102692
TI  - Regulation of Pom cluster dynamics in Myxococcus xanthus.
AB  - Precise positioning of the cell division site is essential for the correct
      segregation of the genetic material into the two daughter cells. In the bacterium
      Myxococcus xanthus, the proteins PomX and PomY form a cluster on the chromosome
      that performs a biased random walk to midcell and positively regulates cell
      division there. PomZ, an ATPase, is necessary for tethering of the cluster to the
      nucleoid and regulates its movement towards midcell. It has remained unclear how
      the cluster dynamics change when the biochemical parameters, such as the
      attachment rates of PomZ dimers to the nucleoid and the cluster, the ATP
      hydrolysis rate of PomZ or the mobility of PomZ interacting with the nucleoid and
      cluster, are varied. To answer these questions, we investigate a one-dimensional
      model that includes the nucleoid, the Pom cluster and PomZ proteins. We find that
      a mechanism based on the diffusive PomZ fluxes on the nucleoid into the cluster
      can explain the latter's midnucleoid localization for a broad parameter range.
      Furthermore, there is an ATP hydrolysis rate that minimizes the time the cluster
      needs to reach midnucleoid. If the dynamics of PomZ on the nucleoid is slow
      relative to the cluster's velocity, we observe oscillatory cluster movements
      around midnucleoid. To understand midnucleoid localization, we developed a semi
      analytical approach that dissects the net movement of the cluster into its
      components: the difference in PomZ fluxes into the cluster from either side, the
      force exerted by a single PomZ dimer on the cluster and the effective friction
      coefficient of the cluster. Importantly, we predict that the Pom cluster
      oscillates around midnucleoid if the diffusivity of PomZ on the nucleoid is
      reduced. A similar approach to that applied here may also prove useful for cargo
      localization in ParABS systems.

PMID- 30102693
TI  - Understanding preferences for HIV care and treatment in Zambia: Evidence from a
      discrete choice experiment among patients who have been lost to follow-up.
AB  - BACKGROUND: In public health HIV treatment programs in Africa, long-term
      retention remains a challenge. A number of improvement strategies exist (e.g.,
      bring services closer to home, reduce visit frequency, expand hours of clinic
      operation, improve provider attitude), but implementers lack data about which to
      prioritize when resource constraints preclude implementing all. We used a
      discrete choice experiment (DCE) to quantify preferences for a number of
      potential clinic improvements to enhance retention. METHODS AND FINDINGS: We
      sought a random sample of HIV patients who were lost to follow-up (defined as >90
      days late for their last scheduled appointment) from treatment facilities in
      Lusaka Province, Zambia. Among those contacted, we asked patients to choose
      between 2 hypothetical clinics in which the following 5 attributes of those
      facilities were varied: waiting time at the clinic (1, 3, or 5 hours), distance
      from residence to clinic (5, 10, or 20 km), ART supply given at each refill (1,
      3, or 5 months), hours of operation (morning only, morning and afternoon, or
      morning and Saturday), and staff attitude ("rude" or "nice"). We used mixed
      effects logistic regression to estimate relative utility (i.e., preference) for
      each attribute level. We calculated how much additional waiting time or travel
      distance patients were willing to accept in order to obtain other desired
      features of care. Between December 9, 2015 and May 31, 2016, we offered the
      survey to 385 patients, and 280 participated (average age 35; 60% female).
      Patients exhibited a strong preference for nice as opposed to rude providers
      (relative utility of 2.66; 95% CI 1.9-3.42; p < 0.001). In a standard willingness
      to wait or willingness to travel analysis, patients were willing to wait 19 hours
      more or travel 45 km farther to see nice rather than rude providers. An
      alternative analysis, in which trade-offs were constrained to values actually
      posed to patients in the experiment, suggested that patients were willing to
      accept a facility located 10 km from home (as opposed to 5) that required 5 hours
      of waiting per visit (as opposed to 1 hour) and that dispensed 3 months of
      medications (instead of 5) in order to access nice (as opposed to rude)
      providers. This study was limited by the fact that attributes included in the
      experiment may not have captured additional important determinants of preference.
      CONCLUSIONS: In this study, patients were willing to expend considerable time and
      effort as well as accept substantial inconvenience in order to access providers
      with a nice attitude. In addition to service delivery redesign (e.g.,
      differentiated service delivery models), current improvement strategies should
      also prioritize improving provider attitude and promoting patient centeredness-an
      area of limited policy attention to date.

PMID- 30102694
TI  - Relationship between perception of smile esthetics and orthodontic treatment in
      Spanish patients.
AB  - One of the main objectives of orthodontic treatment is to achieve an esthetic
      smile. This study set out to analyze differences in the perception of smile
      esthetics among patients before and after receiving orthodontic treatment. 250
      Spanish patients analyzed a single photograph in which, by means of computer
      software, midline diastema, black triangle, gingival margin of the left central
      incisor, and gingival ("gummy") smile were altered. Each patient analyzed these
      images before and after undergoing orthodontic treatment. Patients scored the
      photographs on a scale from 1 to 10. Statistical analyses of each group's level
      of perception were carried out, identifying significant differences in
      evaluations before and after treatment, and in relation to subjects' gender and
      age. Patients presented significant differences in the esthetic perception of
      midline diastema and gummy smile anomalies after they had completed orthodontic
      treatment. Gender influenced the perception of smile esthetics, whereby women
      were significantly more critical of midline diastema, black triangle and gingival
      margin of the upper central incisor than men. The age variable also showed
      significant differences in the perception of midline diastema and black triangle
      anomalies. The perception of smile esthetics of some dental anomalies changes as
      a result of orthodontic treatment. Gender influences the perception of some of
      the dental anomalies studied.

PMID- 30102695
TI  - Low incidence of recurrent Buruli ulcers in treated Australian patients living in
      an endemic region.
AB  - We examined recurrent Buruli ulcer cases following treatment and assumed cure in
      a large cohort of Australian patients living in an endemic area. We report that
      while the recurrence rate was low (2.81 cases/year/1000 population), it remained
      similar to the estimated risk of primary infection within the general population
      of the endemic area (0.85-4.04 cases/year/1,000 population). The majority of
      recurrent lesions occurred in different regions of the body and were separated by
      a median time interval of 44 months. Clinical, treatment and epidemiological
      factors combined with whole genome sequencing of primary and recurrent isolates
      suggests that in most recurrent cases a re-infection was more likely as opposed
      to a relapse of the initial infection. Additionally, all cases occurring more
      than 12 months after commencement of treatment were likely re-infections. Our
      study provides important prognostic information for patients and their health
      care providers concerning the nature and risks associated with recurrent cases of
      Buruli ulcer in Australia.

PMID- 30102696
TI  - A genome-wide association study identifies a susceptibility locus for biliary
      atresia on 2p16.1 within the gene EFEMP1.
AB  - Biliary atresia (BA) is a rare pediatric cholangiopathy characterized by
      fibrosclerosing obliteration of the extrahepatic bile ducts, leading to
      cholestasis, fibrosis, cirrhosis, and eventual liver failure. The etiology of BA
      remains unknown, although environmental, inflammatory, infectious, and genetic
      risk factors have been proposed. We performed a genome-wide association study
      (GWAS) in a European-American cohort of 343 isolated BA patients and 1716
      controls to identify genetic loci associated with BA. A second GWAS was performed
      in an independent European-American cohort of 156 patients with BA and other
      extrahepatic anomalies and 212 controls to confirm the identified candidate BA
      associated SNPs. Meta-analysis revealed three genome-wide significant BA
      associated SNPs on 2p16.1 (rs10865291, rs6761893, and rs727878; P < 5 *10-8),
      located within the fifth intron of the EFEMP1 gene, which encodes a secreted
      extracellular protein implicated in extracellular matrix remodeling, cell
      proliferation, and organogenesis. RNA expression analysis showed an increase in
      EFEMP1 transcripts from human liver specimens isolated from patients with either
      BA or other cholestatic diseases when compared to normal control liver samples.
      Immunohistochemistry demonstrated that EFEMP1 is expressed in cholangiocytes and
      vascular smooth muscle cells in liver specimens from patients with BA and other
      cholestatic diseases, but it is absent from cholangiocytes in normal control
      liver samples. Efemp1 transcripts had higher expression in cholangiocytes and
      portal fibroblasts as compared with other cell types in normal rat liver. The
      identification of a novel BA-associated locus, and implication of EFEMP1 as a new
      BA candidate susceptibility gene, could provide new insights to understanding the
      mechanisms underlying this severe pediatric disorder.

PMID- 30102697
TI  - Campylobacter, a zoonotic pathogen of global importance: Prevalence and risk
      factors in the fast-evolving chicken meat system of Nairobi, Kenya.
AB  - Campylobacteriosis is a leading foodborne zoonosis worldwide, and is frequently
      associated with handling and consumption of poultry meat. Various studies
      indicate that Campylobacter causes a substantial human disease burden in low to
      middle-income countries, but data regarding the organism's epidemiology in
      countries like Kenya are scarce. In sub-Saharan Africa, 3.8 million deaths of
      children under-5 years of age are reported annually. Of those, 25% are caused by
      diarrheal diseases, and Campylobacter is one of the most frequently isolated
      bacteria from diarrheic children. With the growth of urban conglomerates, such as
      Kenya's capital, Nairobi, changes in diets, food production systems, and
      retailing dynamics, it is likely that exposure and susceptibility to this
      pathogen will change. Therefore, the importance of Campylobacter disease burden
      in Kenya may increase further. The objectives of this study were: 1) to determine
      the prevalence of Campylobacter spp. in Nairobi's small-scale chicken farms and
      meat retailers, and 2) to identify potential risk factors associated with its
      presence in those sites. The prevalence data provides the first detailed baseline
      for this pathogen in the urban Kenyan context. The risk factors provide context
      specific insights for disease managers. A cross-sectional study of broiler,
      indigenous chicken farms, and chicken meat retailers, was conducted in a peri
      urban, low to middle-income area (Dagoretti), and a very-low income informal
      settlement (Kibera) of Nairobi. Chicken faeces were collected using one pair of
      boot socks per farm, and 3 raw chicken meat samples were purchased per retailer.
      Samples were cultured for viable Campylobacter spp. using mCCDA, followed by
      blood agar plates in aerobic/microaerobic conditions for prevalence calculations.
      A questionnaire-based survey on sanitary, sourcing and selling practices was
      conducted at each site for risk factor identification using logistic regression
      analyses. A total of 171 farm premises and 53 retailers were sampled and
      interviewed. The prevalence results for Campylobacter spp. were between 33 to 44%
      for broiler and indigenous chicken farms, 60% and 64% for retailers, in Dagoretti
      and Kibera, respectively. Univariable logistic regression showed an association
      between Campylobacter spp. presence and the easiness of cleaning the display
      material used by the retailer. Restricting access to the flock was also
      associated with the pathogen's presence. Multivariable logistic regression
      identified the selling of defrosted meat as a retailer risk factor (OR: 4.69; 95%
      CI: 1.31-19.97), calling for more investigation of the reported repetitive
      freezing-thawing processes and cold chain improvement options. At the farm-level,
      having a pen floor of material not easy to clean was found to increase the risk
      (OR: 2.31; 95%CI: 1.06-5.37). The relatively high prevalence of Campylobacter
      spp. across different areas and value chain nodes indicates a clear human
      exposure risk. The open nature of both small-scale broiler and indigenous chicken
      production practices with low biosecurity, hygiene and informal transactions,
      likely plays a role in this. While gradual improvement of farm biosecurity is
      recommended, risk factors identified suggest that consumer education and
      enforcement of basic food safety principles at the retailer end of the food
      continuum represent key targets for risk reduction in informal settings.

PMID- 30102698
TI  - Prevalence and risk factors for faecal carriage of Extended Spectrum beta
      lactamase producing Enterobacteriaceae among food handlers in lower basic schools
      in West Coast Region of The Gambia.
AB  - BACKGROUND: The isolation of Extended spectrum betalactamase (ESBLs) producing
      Enterobacteriaceae among food handlers and their implication as sources of food
      borne outbreaks are a public health concern. This study seeks to investigate the
      prevalence of faecal carriage of these bacteria among food handlers in the West
      Coast Region of The Gambia. METHOD: This study enrolled 600 participants from 60
      Lower Basic Schools in West Coast Region of the country. Stool samples collected
      from the participants were presumptively screened for the ESBLs producing
      Enterobacteriaceae, using Drigalski agar, supplemented with 2mg/L cefotaxime. The
      bacterial colonies that grew on each Drigalski agar were tested for ESBL
      production by the double disk synergy test as recommended by Clinical and
      Laboratory Standard Institute (CLSI-2015). The confirmatory analysis for ESBL was
      determined as the zone of inhibition of cefotaxime and/or ceftazidime to >=5mm
      from that of cefotaxime /clavulanicacid and/or ceftazidime/clavulanic acid. The
      presumptive screening of isolates for AmpC phenotypes was done by testing the
      organism against cefoxitin. The prevalence of the ESBL carriage was presented in
      percentages. The association of risk factors to the faecal carriage of ESBLs
      producing Enterobacteriaceae was performed by Pearson Chi-squared and Fishers
      Exact at (p <= 0.05). RESULT: The prevalence of faecal carriage ESBL producing
      Enterobacteriaceae among food handlers was 5.0% (28/565). We found50% (14/28)
      and3.57% (1/28) ESBL producing bacteria were presumptive AmpC and carbapenemase
      resistance phenotype. Themost abundant ESBL producing Enterobacteriaceae were
      Klebsiella spp 32.1% (9/28) and Escherichia spp 28.6% (8/28). The use of
      antibiotics in the last 3 months was found to be significantly associated (P =
      0.012) with the faecal carriage of ESBLs producing Enterobacteriaceae.
      CONCLUSION: The prevalence of faecal carriage of ESBLs producing
      Enterobacteriaceae among food handlers in the Gambia is low. The history to use
      of the antibiotics in the last three months was found to be significantly
      associated with this prevalence. Therefore, the institution of a robust
      antimicrobial surveillance and treatment of patients with such infections are
      necessary to curb the spread of these multidrug resistant bacteria in the
      country. Rational prescription and usage of the antibiotics especially
      cephalosporin should be advocated both in public and private health facilities.

PMID- 30102699
TI  - Are two internal thoracic grafts better than one in patients with chronic
      obstructive lung disease? Analysis of 387 cases between 1996-2011.
AB  - OBJECTIVES: Bilateral internal thoracic artery (ITA) grafting is associated with
      improved survival. However, potential survival benefit of using two ITA's in
      patients with chronic lung disease (CLD) is questionable due to their increased
      risk of sternal wound infection (SWI) compared to operations incorporating single
      ITA (SITA). The purpose of this study is to compare early and long-term outcome
      of bilateral internal thoracic artery (BITA) grafting to that of grafting with
      single internal thoracic grafts and vein grafts or radial artery (SITA) in CLD
      patients with multi-vessels coronary disease. METHODS: One hundred and forty
      eight CLD patients who underwent BITA between 1996 and 2011 were compared with
      239 who underwent SITA at the same period. RESULTS: SITA patients were more often
      female, more likely to have insulin treated diabetes (DM), DM with end organ
      damage, neurologic dysfunction and unstable angina. Despite of the difference in
      preoperative characteristics, early mortality (5.4% vs. 5.4%, in the SITA and
      BITA respectively, p = 0 < .999) and occurrences of SWI (6.3% vs 9.5%, p = 0.320)
      and strokes (3.8% vs 5.4%,p = 0.611) were not significantly different between
      groups. BITA patients did not have better Kaplan-Meier 10 year survival (52.8%
      vs. 42.6%, p = 0.088) and after matching, BITA and SITA had similar adjusted
      survival (HR 0.983[95%CI 0.755-1.280] p = 0.901) (cox model). CONCLUSION: Our
      study results suggest that in patients with CLD, the choice of BITA grafting
      technique did not provide survival benefit compared to SITA with other conduits.

PMID- 30102700
TI  - Combinations of DIPs and Dprs control organization of olfactory receptor neuron
      terminals in Drosophila.
AB  - In Drosophila, 50 classes of olfactory receptor neurons (ORNs) connect to 50
      class-specific and uniquely positioned glomeruli in the antennal lobe. Despite
      the identification of cell surface receptors regulating axon guidance, how ORN
      axons sort to form 50 stereotypical glomeruli remains unclear. Here we show that
      the heterophilic cell adhesion proteins, DIPs and Dprs, are expressed in ORNs
      during glomerular formation. Many ORN classes express a unique combination of
      DIPs/dprs, with neurons of the same class expressing interacting partners,
      suggesting a role in class-specific self-adhesion between ORN axons. Analysis of
      DIP/Dpr expression revealed that ORNs that target neighboring glomeruli have
      different combinations, and ORNs with very similar DIP/Dpr combinations can
      project to distant glomeruli in the antennal lobe. DIP/Dpr profiles are dynamic
      during development and correlate with sensilla type lineage for some ORN classes.
      Perturbations of DIP/dpr gene function result in local projection defects of ORN
      axons and glomerular positioning, without altering correct matching of ORNs with
      their target neurons. Our results suggest that context-dependent differential
      adhesion through DIP/Dpr combinations regulate self-adhesion and sort ORN axons
      into uniquely positioned glomeruli.

PMID- 30102701
TI  - Wdr62 is involved in meiotic initiation via activating JNK signaling and
      associated with POI in humans.
AB  - Meiosis is a germ cell-specific division that is indispensable for the generation
      of haploid gametes. However, the regulatory mechanisms of meiotic initiation
      remain elusive. Here, we report that the Wdr62 (WD40-repeat protein 62) is
      involved in meiotic initiation as a permissive factor rather than an instructive
      factor. Knock-out of this gene in a mouse model resulted in meiotic initiation
      defects. Further studies demonstrated that Wdr62 is required for RA-induced Stra8
      expression via the activation of JNK signaling, and the defects in meiotic
      initiation from Wdr62-deficient mice could be partially rescued by JNK1
      overexpression in germ cells. More importantly, two novel mutations of the WDR62
      gene were detected in patients with premature ovarian insufficiency (POI), and
      these mutations played dominant-negative roles in regulating Stra8 expression.
      Hence, this study revealed that Wdr62 is involved in meiotic initiation via
      activating JNK signaling, which displays a novel mechanism for regulating meiotic
      initiation, and mutation of WDR62 is one of the potential etiologies of POI in
      humans.

PMID- 30102702
TI  - SILGGM: An extensive R package for efficient statistical inference in large-scale
      gene networks.
AB  - Gene co-expression network analysis is extremely useful in interpreting a complex
      biological process. The recent droplet-based single-cell technology is able to
      generate much larger gene expression data routinely with thousands of samples and
      tens of thousands of genes. To analyze such a large-scale gene-gene network,
      remarkable progress has been made in rigorous statistical inference of high
      dimensional Gaussian graphical model (GGM). These approaches provide a formal
      confidence interval or a p-value rather than only a single point estimator for
      conditional dependence of a gene pair and are more desirable for identifying
      reliable gene networks. To promote their widespread use, we herein introduce an
      extensive and efficient R package named SILGGM (Statistical Inference of Large
      scale Gaussian Graphical Model) that includes four main approaches in statistical
      inference of high-dimensional GGM. Unlike the existing tools, SILGGM provides
      statistically efficient inference on both individual gene pair and whole-scale
      gene pairs. It has a novel and consistent false discovery rate (FDR) procedure in
      all four methodologies. Based on the user-friendly design, it provides outputs
      compatible with multiple platforms for interactive network visualization.
      Furthermore, comparisons in simulation illustrate that SILGGM can accelerate the
      existing MATLAB implementation to several orders of magnitudes and further
      improve the speed of the already very efficient R package FastGGM. Testing
      results from the simulated data confirm the validity of all the approaches in
      SILGGM even in a very large-scale setting with the number of variables or genes
      to a ten thousand level. We have also applied our package to a novel single-cell
      RNA-seq data set with pan T cells. The results show that the approaches in SILGGM
      significantly outperform the conventional ones in a biological sense. The package
      is freely available via CRAN at https://cran.r-project.org/package=SILGGM.

PMID- 30102703
TI  - Scaling up data curation using deep learning: An application to literature triage
      in genomic variation resources.
AB  - Manually curating biomedical knowledge from publications is necessary to build a
      knowledge based service that provides highly precise and organized information to
      users. The process of retrieving relevant publications for curation, which is
      also known as document triage, is usually carried out by querying and reading
      articles in PubMed. However, this query-based method often obtains unsatisfactory
      precision and recall on the retrieved results, and it is difficult to manually
      generate optimal queries. To address this, we propose a machine-learning assisted
      triage method. We collect previously curated publications from two databases
      UniProtKB/Swiss-Prot and the NHGRI-EBI GWAS Catalog, and used them as a gold
      standard dataset for training deep learning models based on convolutional neural
      networks. We then use the trained models to classify and rank new publications
      for curation. For evaluation, we apply our method to the real-world manual
      curation process of UniProtKB/Swiss-Prot and the GWAS Catalog. We demonstrate
      that our machine-assisted triage method outperforms the current query-based
      triage methods, improves efficiency, and enriches curated content. Our method
      achieves a precision 1.81 and 2.99 times higher than that obtained by the current
      query-based triage methods of UniProtKB/Swiss-Prot and the GWAS Catalog,
      respectively, without compromising recall. In fact, our method retrieves many
      additional relevant publications that the query-based method of UniProtKB/Swiss
      Prot could not find. As these results show, our machine learning-based method can
      make the triage process more efficient and is being implemented in production so
      that human curators can focus on more challenging tasks to improve the quality of
      knowledge bases.

PMID- 30102704
TI  - Evaluation of cultivated and wild genotypes of Lens species under alkalinity
      stress and their molecular collocation using microsatellite markers.
AB  - In this study, 285 lentil genotypes were phenotyped under hydroponic and alkaline
      field conditions. Significant genotypic variation for alkalinity stress was
      observed among the six Lens species screened hydroponically and in the field
      having pH up to 9.1. The crucial parameters, like whole Na+ and K+ contents and
      the Na+/K+ ratio at 40 mM NaHCO3 were found significantly correlated with
      seedling survivability under hydroponics (r = -0.95, r = 0.93 and -0.97).
      Genotypes, ranked on the bases of seed yield, restricted uptake of Na+ with thick
      pith area, increased vascular bundles, less H2O2 production and low Na+/K+ ratio,
      were found important physio-anatomical traits for alkalinity stress tolerance.
      The proper regulation of Na+ uptake was found for maintaining higher K+. This
      relationship is probably the main factor responsible for a better mechanism for
      tolerance to high pH up to 9.1 in tolerant breeding lines PDL-1 and PSL-9
      (cultivars) and ILWL-15, ILWL-192 and ILWL-20 (wild accessions). Based on UPGMA
      dendrogram, all the genotypes were clustered into four diverse groups. DMRT was
      implied within the group to differentiate genotypes based on phenotypic response
      under alkalinity stress. These results can be utilized for selecting diverse
      parents for developing alkalinity tolerant genotypes.

PMID- 30102705
TI  - Shorter-course treatment for Mycobacterium ulcerans disease with high-dose
      rifamycins and clofazimine in a mouse model of Buruli ulcer.
AB  - TRIAL REGISTRATION: ClinicalTrials.gov NCT03474198, NCT01659437.

PMID- 30102707
TI  - The prognostic analysis of different metastatic patterns in advanced liver cancer
      patients: A population based analysis.
AB  - BACKGROUND: The prognostic impact of different distant metastases pattern in
      liver cancer is unexplored still now. The aim of this study is to analyze the
      metastasis patterns and prognosis differences for patients with stage IV liver
      cancers. METHODS: A SEER analysis was performed. Overall survival and cancer
      specific survival were calculated by the Kaplan-Meier method. Multivariable Cox
      regression models were used to further analyze survival outcome and other
      prognostic factors. RESULTS: A total of 37526 eligible cases were retrieved in
      the Surveillance, Epidemiology, and End Results database. Among these patients,
      stage of IV liver cancer accounted for 14.80% (5555/37526) at initial diagnosis.
      Patients who suffered bone, brain or lung metastasis occupied 55.61% (3089/5555).
      Comparing with other two single metastases, the patients with brain metastasis
      exhibited worst overall survival whose mean of survival was 4.758 months.
      Multivariate analysis with Cox hazard regression model showed that metastatic
      site was an independent prognostic factor of overall survival and cancer-specific
      survival in patients with single metastasis (P<0.05). The results of univariate
      analysis showed that metastatic pattern was significantly correlated with overall
      survival (P = 0.038) and cancer-specific survival (P = 0.035) of patients with
      two sites. CONCLUSIONS: Lung was the most common site of single metastasis for
      liver cancers. Patients with bone metastasis had best survival outcome comparing
      with other two distant metastases. Patients with two metastatic sites, where one
      of them is the lung tends to have a slight trend to a worse outcome.

PMID- 30102708
TI  - Estimates of air pollution in Delhi from the burning of firecrackers during the
      festival of Diwali.
AB  - Delhi has had the distinction of being one of the most polluted cities in the
      world, especially in the winter months from October-January. These months
      coincide with the religious festival of Diwali. It is argued that air quality
      gets worse in the aftermath of Diwali on account of firecrackers that get burned
      during the festival. We use hourly data on PM 2.5 particulate concentration from
      2013 to 2017 to estimate the Diwali effect on air quality in Delhi. We improve on
      existing work by using the event study technique as well as a difference-in
      difference regression framework to estimate the Diwali effect on air quality. The
      results suggest that Diwali leads to a small, but statistically significant
      increase in air pollution. The effect is different across locations within Delhi.
      To our knowledge, this is the first causal estimate of the contribution of Diwali
      firecracker burning to air pollution.

PMID- 30102706
TI  - Variability of core microbiota in newly diagnosed treatment-naive paediatric
      inflammatory bowel disease patients.
AB  - BACKGROUND & AIMS: Intestinal microbiota is considered to play a crucial role in
      the aetiology of inflammatory bowel disease (IBD). We aimed to describe faecal
      microbiota composition and dynamics in a large cohort of children with de novo
      (naive) IBD, in comparison to healthy paediatric controls (HC). METHODS: In this
      prospective study, performed at two tertiary centres, faecal samples from newly
      diagnosed, treatment-naive paediatric IBD patients were collected prior to bowel
      cleansing for colonoscopy (t0) and 1, 3 and 6 weeks and 3 months after initiation
      of therapy. The microbial profiles of Crohn's disease (CD) and Ulcerative colitis
      (UC) patients were compared with HC and linked to therapeutic response.
      Microbiota composition was analysed by IS-pro technology. RESULTS: Microbial
      profiles of 104 new IBD-patients (63 CD, 41 UC, median age 14.0 years) were
      compared to 61 HC (median 7.8 years). IBD was mainly characterised by decreased
      abundance of Alistipes finegoldii and Alistipes putredinis, which characterize a
      healthy state microbial core. The classifier including these core species as
      predictors achieved an AUC of the ROC curve of .87. Core bacteria tended to
      regain abundance during treatment, but did not reach healthy levels. CONCLUSION:
      Faecal microbiota profiles of children with de novo CD and UC can be
      discriminated from HC with high accuracy, mainly driven by a decreased abundance
      of species shaping the microbial core in the healthy state. Paediatric IBD can
      therefore be characterized by decreased abundance of certain bacterial species
      reflecting the healthy state rather than by the introduction of pathogens.

PMID- 30102709
TI  - Electrical discharges in water induce spores' DNA damage.
AB  - Bacterial spores are one of the most resilient life forms on earth and are
      involved in many human diseases, such as infectious diarrhea, fatal paralytic
      illnesses and respiratory infections. Here, we investigated the mechanisms
      involved in the death of Bacillus pumilus spores after exposure to electric arcs
      in water. Cutting-edge microscopies at the nanoscale did not reveal any
      structural disorganization of spores exposed to electric arcs. This result
      suggested the absence of physical destruction by a propagating shock wave or an
      exposure to an electric field. However, Pulsed-Field Gel Electrophoresis (PFGE)
      revealed genomic DNA damage induced by UV radiation and Reactive Oxygen Species
      (ROS). UV induced single-strand DNA breaks and thymine dimers while ROS were
      mainly involved in base excision. Our findings revealed a correlation between DNA
      damage and the treatment of spores with electrical discharges.

PMID- 30102710
TI  - Local densities and habitat preference of the critically endangered spotted
      handfish (Brachionichthys hirsutus): Large scale field trial of GPS parameterised
      underwater visual census and diver attached camera.
AB  - The critically endangered spotted handfish (Brachionichthys hirsutus) is
      restricted to a limited number of locations in south-eastern Tasmania, Australia.
      As is often the case for rare species, conducting statistically adequate surveys
      for B. hirsutus can be costly and time consuming due to the low probability of
      encountering individuals. For the first time we used a highly efficient and
      rigorous Global Positioning System (GPS) parameterised underwater visual census
      (GUVC) to survey B. hirsutus abundance within all nine known local populations in
      the Derwent Estuary within one season. In addition, a benthic microhabitat
      assessment was conducted simultaneously using a GoPro(r) camera attached to diver
      to determine B. hirsutus microhabitat preferences. B. hirsutus local populations
      varied between sites, with densities ranging from 1.58 to 43.0 fishes per
      hectare. B. hirsutus demonstrates a strong preference for complex microhabitat
      features, such as depressions and ripple formations filled with biogenic
      substrates (e.g. shells) but avoids simple, low relief microhabitats (e.g. sand
      flats) and areas dominated by ephemeral, filamentous algae. Complex microhabitats
      may enable B. hirsutus to avoid predators, increase forage opportunities or
      provide higher quality spawning sites. This first wide-scale application of GUVC
      for B. hirsutus allowed us to survey a larger number of sites than previously
      possible to provide a robust reference point for future long-term monitoring.

PMID- 30102711
TI  - Dietary soybean protein ameliorates high-fat diet-induced obesity by modifying
      the gut microbiota-dependent biotransformation of bile acids.
AB  - The consumption of soybean protein has well-known favorable metabolic effects
      (e.g., reduced body weight, body fat, hyperglycemia, insulin resistance, hepatic
      steatosis, and lipogenesis). These effects of soy protein have been linked to
      modulation by the gut microbiota; however, the dynamic interplay among these
      factors remains unclear. Accordingly, we examined the metabolic phenotype,
      intestinal BA pool, and the gut microbiome of male C57BL/6 mice that were
      randomized to receive either a regular high-fat diet (HFD) or HFD that contained
      soybean protein isolate (SPI) in place of dairy protein. The intake of SPI
      significantly reduced the HFD-induced weight gain and adipose tissue mass
      accumulation and attenuated hepatic steatosis. Along with an enhancement in the
      secretion of intestinal Glucagon-like peptide-1 (GLP-1), an enlarged cecal BA
      pool with an elevated secondary/primary BA ratio was observed in the mice that
      consumed SPI, while fecal BA excretion remained unaltered. SPI also elicited
      dramatic changes in the gut microbiome, characterized by an expansion of taxa
      that may be involved in the biotransformation of BAs. The observed effects were
      abolished in germ-free (GF) mice, indicating that they were dependent on the
      microbiota. These findings collectively indicate that the metabolic benefits of
      SPI under the HFD regime may arise from a microbiota-driven increase in BA
      transformation and increase in GLP-1 secretion.

PMID- 30102712
TI  - Modelling spatio-temporal patterns of disease for spatially misaligned data: An
      application on measles incidence data in Namibia from 2005-2014.
AB  - BACKGROUND: Making inferences about measles distribution patterns at small area
      level is vital for more focal targeted intervention. However, in statistical
      literature, the analysis of originally collected data on one resolution with the
      purpose to make inferences on a different level of spatial resolution is referred
      to as the misalignment problem. In Namibia the measles data were available in
      aggregated format at regional level for the period 2005 to 2014. This leads to a
      spatial misalignment problem if the purpose is to make decisions at constituency
      level. Moreover, although data on risk covariates of measles could be obtained at
      constituency level, they were not available each year between 2005 and 2014.
      Thus, assuming that covariates were constant through the study period would
      induce measurement errors which might have effects on the analysis results. This
      paper presents a spatio-temporal model through a multi-step approach in order to
      deal with misalignment and measurement error. METHODS: For the period 2005-2014,
      measles data from the Ministry of Health and Social Services (MoHSS) were
      analysed in two steps. First, a multi-step approach was applied to correct
      spatial misalignment in the data. Second, a classical measurement error model was
      fitted to account for measurement errors. The time effects were specified using a
      nonparametric formulation for the linear trend through first order random walk.
      An interaction between area and time was modelled through type I and type II
      interaction structures. RESULTS: The study showed that there was high variation
      in measles risk across constituencies and as well as over the study period (2005
      2014). Furthermore, the risk of measles was found to be associated with (i) the
      number of people aged between 0 and 24 years, (ii) the percentages of women aged
      15-49 with an educational level more than secondary, (iii) the percentages of
      children age 12-23 months who received measles vaccine, (iv) the percentages of
      malnourished children under 5 years, and (vi) the measles cases for each previous
      year. CONCLUSION: The study showed some of the determinants of measles risk and
      revealed areas at high risk through disease mapping. Additionally, the study
      showed a non-linear temporal distribution of measles risk over the study period.
      Finally, it was shown that ignoring the measurement errors may yield misleading
      results. It was recommended that group and geographically targeted intervention,
      prevention and control strategies can be tailored on the basis these findings.

PMID- 30102714
TI  - Efficiently sampling the realizations of bounded, irregular degree sequences of
      bipartite and directed graphs.
AB  - Since 1997 a considerable effort has been spent on the study of the swap (switch)
      Markov chains on graphic degree sequences. All of these results assume some kind
      of regularity in the corresponding degree sequences. Recently, Greenhill and
      Sfragara published a breakthrough paper about irregular normal and directed
      degree sequences for which rapid mixing of the swap Markov chain is proved. In
      this paper we present two groups of results. An example from the first group is
      the following theorem: let [Formula: see text] be a directed degree sequence on n
      vertices. Denote by Delta the maximum value among all in- and out-degrees and
      denote by [Formula: see text] the number of edges in the realization. Assume
      furthermore that [Formula: see text]. Then the swap Markov chain on the
      realizations of [Formula: see text] is rapidly mixing. This result is a slight
      improvement on one of the results of Greenhill and Sfragara. An example from the
      second group is the following: let d be a bipartite degree sequence on the vertex
      set U ? V, and let 0 < c1 <= c2 < |U| and 0 < d1 <= d2 < |V| be integers, where
      c1 <= d(v) <= c2: ?v ? V and d1 <= d(u) <= d2: ?u ? U. Furthermore assume that
      (c2 - c1 - 1)(d2 - d1 - 1) < max{c1(|V| - d2), d1(|U| - c2)}. Then the swap
      Markov chain on the realizations of d is rapidly mixing. A straightforward
      application of this latter result shows that when a random bipartite or directed
      graph is generated under the Erdos-Renyi G(n, p) model with mild assumptions on n
      and p then the degree sequence of the generated graph has, with high probability,
      a rapidly mixing swap Markov chain on its realizations.

PMID- 30102713
TI  - Neuromuscular control of ankle and hip during performance of the star excursion
      balance test in subjects with and without chronic ankle instability.
AB  - BACKGROUND/PURPOSE: Ankle sprains are common and potentially disabling
      musculoskeletal injuries that often lead to chronic ankle instability (CAI). CAI
      has been linked to impairments in postural and neuromuscular control; however,
      inconsistent findings have been reported. Individuals who experience a lateral
      ankle sprain, but do not develop instability, termed copers, may adapt different
      neuromuscular control strategies after injury. This study aimed to compare
      postural control and electromyographic (EMG) activity of hip and ankle muscles
      during the performance of the Star Excursion Balance Test (SEBT) in subjects with
      and without CAI. METHOD: 48 participants were classified into three groups (16
      control, 16 copers, 16 CAI) based on ankle sprain history and Cumberland Ankle
      Instability Tool score. Outcome measures included normalized reach distance,
      center of pressure (COP), and integrated EMG activation of gluteus medius (Gmed),
      gluteus maximus (Gmax), tibialis anterior (TA), and peroneus longus (PL) during
      each reach direction of SEBT. RESULTS: Compared to copers and controls, CAI group
      demonstrated significantly diminished postural control (reach distance and COP
      measures, p< 0.05) and less EMG activity of TA during the anterior direction
      (CAI: 33.1% +/- 10.1% versus copers: 44.8% +/- 12.7% versus controls: 51.7% +/-
      8.4%, p<0.01) and Gmax in the posterolateral direction (CAI: 25.6% +/- 9.4%
      versus copers: 37.5% +/- 13.8% versus controls: 40.2% +/- 17.2%, p = 0.011).
      CONCLUSION: Alteration in proximal and distal muscle activity appears to
      negatively affect postural control and quality of movement, which may lead to
      prolonged functional impairments. Hence, implementing hip and ankle muscle
      exercises in the rehabilitation of ankle instability might benefit these
      patients.

PMID- 30102715
TI  - Strong effects of coral species on the diversity and structure of reef fish
      communities: A multi-scale analysis.
AB  - While there is increasing evidence for habitat specialization in coral reef
      fishes, the extent to which different corals support different fish communities
      is not well understood. Here we quantitatively assess the relative importance of
      different coral species in structuring fish communities and evaluate whether
      sampling scale and coral colony size affect the perceived strength of fish
      habitat relationships. Fish communities present on colonies of eight coral
      species (Porites cylindrica, Echinopora horrida, Hydnophora rigida, Stylophora
      pistillata, Seriatopora hystrix, Acropora formosa, A. tenuis and A. millepora)
      were examined in the Lizard Island lagoon, Great Barrier Reef, Australia.
      Additionally, the differences in fish communities supported by three coral
      species (P. cylindrica, E. horrida, H. rigida) were investigated at three spatial
      scales of sampling (2x2 m, 1x1 m, 0.5x0.5 m). Substantial differences in fish
      communities were observed across the different coral species, with E. horrida and
      H. rigida supporting the most fish species and individuals. Coral species
      explained more of the variability in fish species richness (20.9-53.6%), than in
      fish abundance (0-15%). Most coral species supported distinctive fish
      communities, with dissimilarities ranging from 50 to 90%. For three focal coral
      species, a greater amount of total variation in fish species richness and fish
      abundance was evident at a larger scale of sampling. Together, these results
      indicate that the structure of reef fish communities is finely tuned to coral
      species. Loss of preferred coral species could have profound effects on reef fish
      biodiversity, potentially more so than would be predicted on the basis of
      declining coral cover alone.

PMID- 30102716
TI  - Mid regional pro-adrenomedullin for the prediction of organ failure in infection.
      Results from a single centre study.
AB  - Biomarkers are widely used to confirm the presence of infection. However, it
      would be of the greatest importance to predict in advance the occurrence or
      worsening of organ dysfunction in infected patients allowing timely antibiotic
      escalation. This study investigates the ability of procalcitonin (PCT) and MR
      proADM to predict the transition to sepsis in infected patients. The study was
      conducted in a neurointensive care unit over a three-month period. We included
      both patients with and without infection to investigate the specificity of organ
      dysfunction prediction in infected patients. Daily measurement of PCT and MR
      proADM, SOFA, Pitt, and CPIS were performed. To measure the correlation between
      each biomarker and each severity score, linear mixed-effects models were
      developed. For each biomarker-score combination we tested the correlation of the
      score with the biomarker measured one and two days before, the same day, and the
      day after. Sixty-four critically ill patients, 31 with infection, were enrolled.
      The statistically significant biomarker-score combinations were PCT-SOFA, MR
      proADM-SOFA, MR-proADM-Pitt, and MR-proADM-CPIS. The MR-proADM models predicting
      Pitt and CPIS variations with 24-hour anticipation showed the best fit. The
      scores increased by 0.6 +/- 0.3 and 0.4 +/- 0.2 for each unitary biomarker
      increase, respectively. The MR-proADM-SOFA combinations were equivalent when the
      biomarker was measured the day before or the same day (score increases were 1.5
      +/- 0.4 and 1.9 +/- 0.4, respectively). The PCT-SOFA model had the best fit when
      PCT was measured the same day of the score. There was no difference in the
      predictive ability of the biomarker in infected and non-infected patients. This
      was a pivotal study conducted in a single neurointensive centre on a limited
      number of patients, and as such it does not provide definitive conclusions. PR
      proADM predicted occurrence and worsening of organ failure in critically ill
      patients with and without infection. The combination with infection diagnostic
      biomarkers such as PCT would allow predicting evolution to sepsis in infected
      patients.

PMID- 30102718
TI  - Who will win where and why? An ecophysiological dissection of the competition
      between a tropical pasture grass and the invasive weed Bracken over an elevation
      range of 1000 m in the tropical Andes.
AB  - In tropical agriculture, the vigorously growing Bracken fern causes severe
      problems by invading pastures and out-competing the common pasture grasses. Due
      to infestation by that weed, pastures are abandoned after a few years, and as a
      fatal consequence, the biodiversity-rich tropical forest is progressively cleared
      for new grazing areas. Here we present a broad physiological comparison of the
      two plant species that are the main competitors on the pastures in the tropical
      Ecuadorian Andes, the planted forage grass Setaria sphacelata and the weed
      Bracken (Pteridium arachnoideum). With increasing elevation, the competitive
      power of Bracken increases as shown by satellite data of the study region. Using
      data obtained from field measurements, the annual biomass production of both
      plant species, as a measure of their competitive strength, was modeled over an
      elevational gradient from 1800 to 2800 m. The model shows that with increasing
      elevation, biomass production of the two species shifts in favor of Bracken
      which, above 1800 m, is capable of outgrowing the grass. In greenhouse
      experiments, the effects on plant growth of the presumed key variables of the
      elevational gradient, temperature and UV radiation, were separately analyzed. Low
      temperature, as well as UV irradiation, inhibited carbon uptake of the C4-grass
      more than that of the C3-plant Bracken. The less temperature-sensitive
      photosynthesis of Bracken and its effective protection from UV radiation
      contribute to the success of the weed on the highland pastures. In field samples
      of Bracken but not of Setaria, the content of flavonoids as UV-scavengers
      increased with the elevation. Combining modeling with measurements in greenhouse
      and field allowed to explain the invasive growth of a common weed in upland
      pastures. The performance of Setaria decreases with elevation due to suboptimal
      photosynthesis at lower temperatures and the inability to adapt its cellular UV
      screen.

PMID- 30102717
TI  - Subtyping patients with somatic tinnitus: Modulation of tinnitus and history for
      somatic dysfunction help identify tinnitus patients with temporomandibular joint
      disorders.
AB  - OBJECTIVE: Determine in a cohort of patients with normal hearing and chronic
      tinnitus if self-reported history for temporomandibular joint (TMJ) dysfunction
      and a positive modulation of tinnitus in the TMJ region could be suggestive of an
      underlying TMJ disorder. PATIENTS AND METHODS: The study included 226 patients
      presenting to the Head and Neck Service of our University Hospital. Following
      audiological and somatic tinnitus evaluation, patients were divided into two
      groups. The study group (n = 134) included subjects that met both the following
      criteria: A) a self-reported history for TMJ dysfunction and B) a positive
      modulation of tinnitus following somatic maneuvers in the TMJ region. The control
      group (n = 92) included patients with similar demographic and tinnitus
      characteristics that did not meet the proposed criteria for somatic tinnitus.
      Afterwards, patients underwent clinical TMJ evaluation in the Service of Clinical
      Gnathology of our University. RESULTS: One hundred thirty-one patients (57.9%)
      received a clinical diagnosis of TMJ disorder according to DC/TMD Axis I; 79.1%
      in the study group and 27.2% in the control group. Ninety-five (42.1%) patients
      were negative for TMJ disorders; 20.9% in the study group and 72.8% in the
      control group. A significantly higher number of TMJ disorders was found in
      patients in the study group compared to the control group (p<0.0001). Most
      patients had joint disorders (67.2%), followed by other (29.8%) and pain
      disorders (29%). Logistic regression analysis in the study group showed that
      female gender was more prevalent in patients with TMJ disorders. CONCLUSION: Our
      findings in patients with chronic tinnitus and normal hearing suggest that self
      reported history for somatic dysfunction and modulation of tinnitus, when
      occurring simultaneously in the TMJ region, can be useful to preliminarily
      identify patients with TMJ disorders.

PMID- 30102719
TI  - MicroRNA regulation in blood cells of renal transplanted patients with
      interstitial fibrosis/tubular atrophy and antibody-mediated rejection.
AB  - Interstitial fibrosis/tubular atrophy (IFTA) is associated with reduced allograft
      survival, whereas antibody-mediated rejection (ABMR) is the major cause for renal
      allograft failure. To identify specific microRNAs and their regulation involved
      in these processes, total RNA from blood cells of 16 kidney transplanted (KTx)
      patients with ABMR, stable graft function (SGF) and with T-cell mediated
      rejection (TCMR) was isolated. MicroRNA expression was determined by high
      throughput sequencing. Differentially expressed candidate microRNAs were analyzed
      with RT-PCR in patients with SGF (n = 53), urinary tract infection (UTI) (n =
      17), borderline rejection (BL) (n = 19), TCMR (n = 40), ABMR (n = 22) and IFTA (n
      = 30). From the 301 detected microRNAs, 64 were significantly regulated between
      the three cohorts. Selected candidate microRNAs miR-223-3p, miR-424-3p and miR
      145-5p distinguished TCMR and ABMR from SGF, but not from other pathologies. Most
      importantly, miR-145-5p expression in IFTA patients was significantly
      downregulated and displayed a high diagnostic accuracy compared to SGF alone (AUC
      = 0.891) and compared to SGF, UTI, BL, TCMR and ABMR patients combined (AUC =
      0.835), which was verified by cross-validation. The identification of miR-145-5p
      as IFTA specific marker in blood constitutes the basis for evaluating this
      potentially diagnostic microRNA as biomarker in studies including high numbers of
      patients and different pathologies and also the further analysis of fibrosis
      causing etiologies after kidney transplantation.

PMID- 30102721
TI  - Emotions evoked by exposure to footstep noise in residential buildings.
AB  - In the present study, the effect of footstep noise on emotions was investigated.
      This study used noise stimulus of human footsteps throughout the study. First,
      Korean emotion lexicons were collected from narratives of residents living in
      multi-family housing buildings. The lexicons were then classified into four
      emotion clusters, with three expressing negative emotions (anger, dislike, and
      pain) and the fourth depicting empathy. Since self-reported annoyance has long
      been investigated as one of the major non-auditory responses to noise, annoyance
      was measured along with affective responses in a laboratory experiment with
      varying noise levels. The findings revealed that the emotion and noise annoyance
      experienced by the participants were significantly affected by noise levels. All
      clusters expressing negative emotions showed strong correlations with noise
      annoyance, whereas that representing empathy showed the weakest correlation.
      Noise sensitivity and attitudes to the noise source were observed as possible
      moderators in emotional responses and annoyance ratings.

PMID- 30102720
TI  - Engineered ferritin for lanthanide binding.
AB  - Ferritin H-homopolymers have been extensively used as nanocarriers for diverse
      applications in the targeted delivery of drugs and imaging agents, due to their
      unique ability to bind the transferrin receptor (CD71), highly overexpressed in
      most tumor cells. In order to incorporate novel fluorescence imaging properties,
      we have fused a lanthanide binding tag (LBT) to the C-terminal end of mouse H
      chain ferritin, HFt. The HFt-LBT possesses one high affinity Terbium binding site
      per each of the 24 subunits provided by six coordinating aminoacid side chains
      and a tryptophan residue in its close proximity and is thus endowed with strong
      FRET sensitization properties. Accordingly, the characteristic Terbium emission
      band at 544 nm for the HFt-LBT Tb(III) complex was detectable upon excitation of
      the tag enclosed at two order of magnitude higher intensity with respect to the
      wtHFt protein. X-ray data at 2.9 A and cryo-EM at 7 A resolution demonstrated
      that HFt-LBT is correctly assembled as a 24-mer both in crystal and in solution.
      On the basis of the intrinsic Tb(III) binding properties of the wt protein, 32
      additional Tb(III) binding sites, located within the natural iron binding sites
      of the protein, were identified besides the 24 Tb(III) ions coordinated to the
      LBTs. HFt-LBT Tb(III) was demonstrated to be actively uptaken by selected tumor
      cell lines by confocal microscopy and FACS analysis of their FITC derivatives,
      although direct fluorescence from Terbium emission could not be singled out with
      conventional, 295-375 nm, fluorescence excitation.

PMID- 30102722
TI  - A network perspective of engaging patients in specialist and chronic illness
      care: The 2014 International Health Policy Survey.
AB  - BACKGROUND: Patient engagement helps to improve health outcomes and health care
      quality. However, the overall relationships among patient engagement measures and
      health outcomes remain unclear. This study aims to integrate expert knowledge and
      survey data for the identification of measures that have extensive associations
      with other variables and can be prioritized to engage patients. METHODS: We used
      the 2014 International Health Policy Survey (IHPS), which provided information on
      elder adults in 11 countries with details in patient characteristics, healthcare
      experiences, and patient-physician communication. Patient engagement or support
      was measured with eight variables including patients' treatment choices,
      involvement, and treatment priority setting. Three types of care were identified:
      primary, specialist and chronic illness care. Specialists were doctors
      specializing in one area of health care. Chronic illness included eight chronic
      conditions surveyed. Expert knowledge was used to assist variable selection. We
      used Bayesian network models consisting of nodes that represented variables of
      interest and arcs that represented their relationships. RESULTS: Among 25,530
      participants, the mean age was 68.51 years and 57.40% were females. The
      distributions of age, sex, education, and patient engagement were significantly
      different across countries. For chronic illness care, written plans provided by
      professionals were linked to treatment feasibility and helpfulness. Whether
      professionals contacted patients was associated with the availability of
      professionals they could reach for chronic illness care. For specialist care, if
      specialists provided treatment choices, patients were more likely to be involved
      and discuss about what mattered to them. CONCLUSION: The strategies to engage
      patients may depend on the types of care, specialist or chronic illness care. For
      the study on the observational IHPS data, network modeling is useful to integrate
      expert knowledge. We suggest considering other theory-based patient engagement in
      major surveys, as well as engaging patients in their healthcare by providing
      written plans and actively communicating with patients for chronic illnesses, and
      encouraging specialists to discuss and provide treatment options.

PMID- 30102723
TI  - Susceptibility to audio signals during autonomous driving.
AB  - We investigate how susceptible human drivers are to auditory signals in three
      situations: when stationary, when driving, or when being driven by an autonomous
      vehicle. Previous research has shown that human susceptibility is reduced when
      driving compared to when being stationary. However, it is not known how
      susceptible humans are under autonomous driving conditions. At the same time,
      good susceptibility is crucial under autonomous driving conditions, as such
      systems might use auditory signals to communicate a transition of control from
      the automated vehicle to the human driver. We measured susceptibility using a
      three-stimulus auditory oddball paradigm while participants experienced three
      driving conditions: stationary, autonomous, or driving. We studied susceptibility
      through the frontal P3 (fP3) Electroencephalography Event-Related Potential
      response (EEG ERP response). Results show that the fP3 component is reduced in
      autonomous compared to stationary conditions, but not as strongly as when
      participants drove themselves. In addition, the fP3 component is further reduced
      when the oddball task does not require a response (i.e., in a passive condition,
      versus active). The implication is that, even in a relatively simple autonomous
      driving scenario, people's susceptibility of auditory signals is not as high as
      would be beneficial for responding to auditory stimuli.

PMID- 30102724
TI  - A new biomarker candidate for spinal muscular atrophy: Identification of a
      peripheral blood cell population capable of monitoring the level of survival
      motor neuron protein.
AB  - Spinal muscular atrophy (SMA) is a severe genetic neuromuscular disorder caused
      by insufficiency of functional survival motor neuron (SMN) protein. Several
      clinical trials have been conducted with the aim of upregulating the expression
      of the SMN protein in SMA patients. In order to evaluate the efficiency of these
      SMN-targeted approaches, it has become necessary to verify SMN protein levels in
      the cells of SMA patients. Accordingly, we have developed a method allowing the
      evaluation of the functional SMN protein with < 1.5 mL of peripheral blood using
      imaging flow cytometry. The expression of SMN protein in CD3+, CD19+, and CD33++
      cells obtained from SMA patients, was significantly reduced compared with that in
      cells from control subjects. In spot analysis of CD33++ cells, the intensities of
      SMN spots were significantly reduced in SMA subjects, when compared with that in
      controls. Therefore, SMN spots implied the presence of functional SMN protein in
      the cell nucleus. To our knowledge, our results are the first to demonstrate the
      presence of functional SMN protein in freshly isolated peripheral blood cells. We
      anticipate that SMN spot analysis will become the primary endpoint assay for the
      evaluation and monitoring of therapeutic intervention, with SMN serving as a
      reliable biomarker of therapeutic efficacy in SMA patients.

PMID- 30102726
TI  - Association of weight gain and fifteen adipokines with declining beta-cell
      function in Mexican Americans.
AB  - Obesity and adipokines are associated with development of type 2 diabetes.
      However, limited longitudinal studies have examined their roles on declining beta
      cell function over time. This report assessed three adiposity measures (BMI,
      percent body fat, trunk fat), insulin resistance, and fifteen adipokines in
      relationship to longitudinal change in beta-cell function measured by disposition
      index (DI) from frequently-sampled-intravenous-glucose-tolerance testing. The
      results showed that three factors were significantly and independently associated
      with rate of change in DI over time: rate of change in BMI (negative), rate of
      change in IL-6 (negative), and baseline adiponectin (positive). The association
      was the strongest for changing BMI and was largely explained by changing insulin
      resistance; the association with changing IL-6 was also largely explained by
      changing insulin resistance. Baseline adiponectin remained positively associated
      after adjustment for changing insulin resistance, suggesting an independent
      effect of adiponectin to preserve or improve beta-cell function. These findings
      provide evidence and potential mechanisms for the role of obesity in promoting
      beta-cell dysfunction, highlighting the potential importance of mitigating
      obesity and its metabolic effects in preventing and treating type 2 diabetes.

PMID- 30102725
TI  - Cancer- and behavior-related genes are targeted by selection in the Tasmanian
      devil (Sarcophilus harrisii).
AB  - Devil Facial Tumor Disease (DFTD) is an aggressive cancer notorious for its rare
      etiology and its impact on Tasmanian devil populations. Two regions underlying an
      evolutionary response to this cancer were recently identified using genomic time
      series pre- and post-DTFD arrival. Here, we support that DFTD shaped the genome
      of the Tasmanian devil in an even more extensive way than previously reported. We
      detected 97 signatures of selection, including 148 protein coding genes having a
      human orthologue, linked to DFTD. Most candidate genes are associated with cancer
      progression, and an important subset of candidate genes has additional influence
      on social behavior. This confirms the influence of cancer on the ecology and
      evolution of the Tasmanian devil. Our work also demonstrates the possibility to
      detect highly polygenic footprints of short-term selection in very small
      populations.

PMID- 30102727
TI  - Essential role of Plasmodium perforin-like protein 4 in ookinete midgut passage.
AB  - Pore forming proteins such as those belonging to the membrane attack/perforin
      (MACPF) family have important functions in many organisms. Of the five MACPF
      proteins found in Plasmodium parasites, three have functions in cell passage and
      one in host cell egress. Here we report an analysis of the perforin-like protein
      4, PPLP4, in the rodent parasite Plasmodium berghei. We found that the protein is
      expressed only in the ookinete, the invasive stage of the parasite formed in the
      mosquito midgut. Transcriptional analysis revealed that expression of the pplp4
      gene commences during ookinete development. The protein was detected in retorts
      and mature ookinetes. Using two antibodies, the protein was found localized in a
      dotted pattern, and 3-D SIM super-resolution microcopy revealed the protein in
      the periphery of the cell. Analysis of a C-terminal mCherry fusion of the protein
      however showed mainly cytoplasmic label. A pplp4 null mutant formed motile
      ookinetes, but these were unable to invade and traverse the midgut epithelium
      resulting in severely impaired oocyst formation and no transmission to naive
      mice. However, when in vitro cultured ookinetes were injected into the thorax of
      the mosquito, thus by-passing midgut passage, sporozoites were formed and the
      mutant parasites were able to infect naive mice. Taken together, our data show
      that PPLP4 is required only for ookinete invasion of the mosquito midgut. Thus
      PPLP4 has a similar role to the previously studied PPLP3 and PPLP5, raising the
      question why three proteins with MACPF domains are needed for invasion by the
      ookinete of the mosquito midgut epithelium.

PMID- 30102728
TI  - Computational simulation of aqueous humour dynamics in the presence of a
      posterior-chamber versus iris-fixed phakic intraocular lens.
AB  - PURPOSE: To compare aqueous humour (AH) dynamics in the presence of a
      precrystalline (Implantable Collamer Lens(r); ICL) or iris-fixed (Artiflex(r))
      phakic intraocular lens (PIOL). METHODS: By computational fluid dynamics
      simulation, AH flow was modelled through a peripheral iridotomy (PI) or central
      lens hole (both 360 MUm) in the presence of an Artiflex or ICL lens,
      respectively. The impacts of AH flow were then determined in terms of wall shear
      stress (WSS) produced on the endothelium or crystalline lens. Effects were also
      modelled for different scenarios of pupil diameter (PD 3.5 or 5.5 mm), ICL vault
      (100, 350, 800 MUm) and number of Artiflex iridotomies (1 or 2) and location (12
      or 6 o'clock). RESULTS: For a PD of 3.5 mm, AH volumes flowing from the posterior
      to the anterior chamber were 37.6% of total flow through the lens hole (ICL) and
      84.2% through PI (Artiflex). For an enlarged PD (5.5 mm), corresponding values
      were 10.3% and 81.9% respectively, so PI constitutes a very efficient way of
      evacuating AH. Central endothelial WSS in Pa was lower for the large vault ICL
      and the Artiflex (1-03 and 1.1-03 respectively) compared to the PIOL-free eye
      (1.6-03). Crystalline lens WSS was highest for the lowest vault ICL (1-04).
      CONCLUSIONS: AH flow varied according to the presence of a precrystalline or iris
      fixed intraocular lens. Endothelial WSS was lower for an implanted ICL with large
      vault and Artiflex than in the PIOL-free eye, while highest crystalline WSS was
      recorded for the lowest vault ICL.

PMID- 30102729
TI  - Identification of induced mutations in hexaploid wheat genome using exome capture
      assay.
AB  - Wheat is a staple food crop of many countries. Improving resilience to biotic and
      abiotic stresses remain key breeding targets. Among these, rust diseases are the
      most detrimental in terms of depressing wheat production. In the present study,
      chemical mutagenesis was used to induce mutations in the wheat variety NN-Gandum
      1. This cultivar is moderately resistant to leaf and yellow rust. The aim of
      mutagenesis was to improve resistance to the disease as well as to study function
      of genes conferring resistance to the disease. In the present investigation, a
      0.8% EMS dose was found optimum for supporting 45-55% germination of NN-Gandum-1.
      A total of 3,634 M2 fertile plants were produced from each of the M1 plant. Out
      of these, 33 (0.91%) and 20 plants (0.55%) showed absolute resistance to leaf and
      yellow rust, respectively. While 126 (3.46%) and 127 plants (3.49%) exhibited
      high susceptibility to the leaf and yellow rust, respectively. In the M4
      generation, a total of 11 M4 lines (nine absolute resistant and two highly
      susceptible) and one wild type were selected for NGS-based exome capture assay. A
      total of 104,779 SNPs were identified that were randomly distributed throughout
      the wheat sub genomes (A, B and D). Induced mutations in intronic sequences
      predominated. The highest total number of SNPs detected in this assay were mapped
      to chr.2B (14,273 SNPs), which contains the highest number of targeted base pairs
      in the assay. The average mutation density across all regions interrogated was
      estimated to be one mutation per 20.91 Mb. The highest mutation frequency was
      found in chr.2D (1/11.7 kb) and the lowest in chr.7D (1/353.4 kb). Out of the
      detected mutations, 101 SNPs were filtered using analysis criteria aimed to
      enrich for mutations that may affect gene function. Out of these, one putative
      SNP detected in Lr21 were selected for further analysis. The SNP identified in
      chimeric allele (Lr21) of a resistant mutant (N1-252) was located in a NBS domain
      of chr.1BS at 3.4 Mb position. Through computational analysis, it was
      demonstrated that this identified SNP causes a substitution of glutamic acid with
      alanine, resulting in a predicted altered protein structure. This mutation,
      therefore, is a candidate for contributing to the resistance phenotype in the
      mutant line. Based on this work, we conclude that the wheat mutant resource
      developed is useful as a source of novel genetic variation for forward-genetic
      screens and also as a useful tool for gaining insights into the important
      biological circuits of different traits of complex genomes like wheat.

PMID- 30102731
TI  - Motor planning error in Parkinson's disease and its clinical correlates.
AB  - This study aimed to investigate (a) motor planning difficulty by using a two-step
      test in Parkinson's disease (PD) compared with age-matched healthy subjects and
      (b) the relationship between motor planning difficulty and clinical factors. The
      two-step test was performed by 58 patients with PD with Hoehn & Yahr (H&Y) stage
      I-IV and 110 age-matched healthy older adult controls. In the two-step test, the
      participants estimated the two-step distance with maximum effort. Subsequently,
      they performed the actual two-step trial to measure the actual maximum distance.
      We calculated the accuracy of the estimation (estimated distance minus actual
      distance). In both groups, subjects who estimated >5 cm were defined as the
      overestimation group, and those who estimated <5 cm over- and underestimation
      were defined as the non-overestimation group. The overestimation group consisted
      of 17 healthy older adults (15.5%) and 23 patients with PD (39.7%). The number of
      patients with PD with overestimation was significantly more than that of healthy
      controls by Chi-squared test. H&Y stage and the Unified Parkinson's Disease
      Rating Scale (UPDRS) part II and III scores in overestimation group in PD
      patients were significantly higher than those in overestimation group in PD
      patients. Moreover, multiple regression using H&Y stage and UPDRS parts II and
      III as independent variables showed that the UPDRS part II score was the only
      related factor for the estimation error distance. Estimation error distance was
      significant correlated with UPDRS parts II and III. Patients with PD easily have
      higher rates of motor-related overestimation than age-matched healthy controls.
      In addition, UPDRS parts II and III expressed ability of activities of daily
      living and motor function as influences on motor-related overestimation.
      Particularly, multiple regression indicated that UPDRS part II directly showed
      the ability of daily living as an essential factor for overestimation.

PMID- 30102730
TI  - The effect of Tmem135 overexpression on the mouse heart.
AB  - Tissues with high-energy demand including the heart are rich in the energy
      producing organelles, mitochondria, and sensitive to mitochondrial dysfunction.
      While alterations in mitochondrial function are increasingly recognized in
      cardiovascular diseases, the molecular mechanisms through which changes in
      mitochondria lead to heart abnormalities have not been fully elucidated. Here, we
      report that transgenic mice overexpressing a novel regulator of mitochondrial
      dynamics, transmembrane protein 135 (Tmem135), exhibit increased fragmentation of
      mitochondria and disease phenotypes in the heart including collagen accumulation
      and hypertrophy. The gene expression analysis showed that genes associated with
      ER stress and unfolded protein response, and especially the pathway involving
      activating transcription factor 4, are upregulated in the heart of Tmem135
      transgenic mice. It also showed that gene expression changes in the heart of
      Tmem135 transgenic mice significantly overlap with those of aged mice in addition
      to the similarity in cardiac phenotypes, suggesting that changes in mitochondrial
      dynamics may be involved in the development of heart abnormalities associated
      with aging. Our study revealed the pathological consequence of overexpression of
      Tmem135, and suggested downstream molecular changes that may underlie those
      disease pathologies.

PMID- 30102732
TI  - Implications of accounting for management intensity on carbon and nitrogen
      balances of European grasslands.
AB  - European managed grasslands are amongst the most productive in the world. Besides
      temperature and the amount and timing of precipitation, grass production is also
      highly controlled by applications of nitrogen fertilizers and land management to
      sustain a high productivity. Since management characteristics of pastures vary
      greatly across Europe, land-use intensity and their projections are critical
      input variables in earth system modeling when examining and predicting the
      effects of increasingly intensified agricultural and livestock systems on the
      environment. In this study, we aim to improve the representation of pastures in
      the dynamic global vegetation model LPJ-GUESS. This is done by incorporating
      daily carbon allocation for grasses as a foundation to further implement daily
      land management routines and land-use intensity data into the model to
      discriminate between intensively and extensively used regions. We further compare
      our new simulations with leaf area index observations, reported regional
      grassland productivity, and simulations conducted with the vegetation model
      ORCHIDEE-GM. Additionally, we analyze the implications of including pasture
      fertilization and daily management compared to the standard version of LPJ-GUESS.
      Our results demonstrate that grassland productivity cannot be adequately captured
      without including land-use intensity data in form of nitrogen applications. Using
      this type of information improved spatial patterns of grassland productivity
      significantly compared to standard LPJ-GUESS. In general, simulations for net
      primary productivity, net ecosystem carbon balance and nitrogen leaching were
      considerably increased in the extended version. Finally, the adapted version of
      LPJ-GUESS, driven with projections of climate and land-use intensity, simulated
      an increase in potential grassland productivity until 2050 for several agro
      climatic regions, most notably for the Mediterranean North, the Mediterranean
      South, the Atlantic Central and the Atlantic South.

PMID- 30102733
TI  - Phylogenetic and antimicrobial resistance gene analysis of Salmonella Typhimurium
      strains isolated in Brazil by whole genome sequencing.
AB  - Whole genome sequencing (WGS) has been used as a powerful technology for
      molecular epidemiology, surveillance, identification of species and serotype,
      identification of the sources of outbreaks, among other purposes. In Brazil,
      there is relatively few epidemiological data on Salmonella. In this study, 90
      Salmonella Typhimurium strains had their genome sequenced to uncover the
      diversity of Salmonella Typhimurium isolated from humans and food, between 1983
      and 2013, from different geographic regions in Brazil based on single nucleotide
      polymorphism (SNP) analysis. A total of 39 resistance genes were identified, such
      as aminoglycoside, tetracycline, sulfonamide, trimethoprim, beta-lactam,
      fluoroquinolone, phenicol and macrolide, as well as the occurrence of point
      mutations in some of the genes such as gyrA, gyrB, parC and parE. A total of 65
      (72.2%) out of 90 S. Typhimurium strains studied were phenotypically resistant to
      sulfonamides, 44 (48.9%) strains were streptomycin resistant, 27 (30%) strains
      were resistant to tetracycline, 21 (23.3%) strains were gentamicin resistant, and
      seven (7.8%) strains were resistant to ceftriaxone. In the gyrA gene, it was
      observed the following amino acid substitutions: Asp(87)->Gly, Asp(87)->Asn,
      Ser(83)->Phe, Ser(83)->Tyr. Phylogenetic results placed the 90 S. Typhimurium
      strains into two major clades suggesting the existence of a prevalent subtype,
      likely more adapted, among strains isolated from humans, with some diversity in
      subtypes in foods. The variety and prevalence of resistant genes found in these
      Salmonella Typhimurium strains reinforces their potential hazard for humans and
      the risk in foods in Brazil.

PMID- 30102734
TI  - First report of Anaplasma marginale infection in goats, Brazil.
AB  - Anaplasma marginale, the causative agent of bovine anaplasmosis, is a tick-borne
      bacterium that causes significant economic losses for cattle industries and is
      increasingly being detected in other animal species. Rhipicephalus microplus is
      the main vector of this bacterium and may be found parasitizing small ruminants.
      In northeastern Brazil, multispecies grazing is a common family subsistence
      practice on smallholder farms possibly facilitating interspecies transmission of
      pathogens. Considering that A. marginale infection has been previously
      molecularly described in sheep, this study has aimed to estimate the prevalence
      of A. marginale and factors associated with the infection in goats from
      northeastern Brazil. A total of 403 goat blood samples were included in the
      study. An epidemiological questionnaire was applied to each farm owner addressing
      age, gender, presence of ticks and multispecies grazing. All samples were
      screened for A. marginale- and A. ovis-infection using primers targeting the
      Anaplasma spp. msp4 gene. The identity of A. marginale in the blood was confirmed
      by PCR amplification of msp5 followed by sequencing. Anaplasma spp. were
      differentiated by sequencing of the repeat region of the msp1alpha gene. For the
      statistical analysis the Chi-square or the Fisher's exact test was used to verify
      association of the individual factors (age, gender, presence of ticks, and
      multispecies grazing) with Anaplasma spp. infection. We report the first
      molecular detection of A. marginale in goats from northeastern Brazil, based on
      msp1alpha, msp4 and msp5 gene sequencing analysis. Sequencing of the detected A.
      marginale msp1alpha gene revealed the F repeat. Amblyomma parvum and R. microplus
      were found feeding on animals.

PMID- 30102735
TI  - Phylogeographic analysis of the full genome of Sweepovirus to trace virus
      dispersal and introduction to Korea.
AB  - Sweet potato is a vegetatively propagated crop that is produced for both growth
      in Korean fields and for export out of the country. The viruses that are present
      in introduced sweet potatoes can spread both domestically and to foreign
      countries. Determining the time and path of virus movement could help curtail its
      spread and prevent future dispersal of related viruses. Determining the
      consequences of past virus and sweet potato dispersal could provide insight into
      the ecological and economic risks associated with other sweet potato-infecting
      viral invasions. We therefore applied Bayesian phylogeographic inferences and
      recombination analyses of the available Sweepovirus sequences (including 25
      Korean Sweepovirus genomes) and reconstructed a plausible history of Sweepovirus
      diversification and movement across the globe. The Mediterranean basin and
      Central America were found to be the launchpad of global Sweepovirus dispersal.
      Currently, China and Brazil are acting as convergence regions for Sweepoviruses.
      Recently reported Korean Sweepovirus isolates were introduced from China in a
      recent phase and the regions around China and Brazil continue to act as centers
      of Sweepovirus diversity and sites of ongoing Sweepovirus evolution. The evidence
      indicates that the region is an epidemiological hotspot, which suggests that
      novel Sweepovirus variants might be found.

PMID- 30102736
TI  - Transcriptomic analysis of drought stress responses of sea buckthorn (Hippophae
      rhamnoidessubsp. sinensis) by RNA-Seq.
AB  - Sea buckthorn is one of the most important eco-economic tree species in China due
      to its ability to grow and produce acceptable yields under limited water and
      fertilizer availability. In this study, the differentially expressed genes under
      drought stress (DS) of sea buckthorn were identified and compared with control
      (CK) by RNA-Seq. A total of 122,803 unigenes were identified in sea buckthorn,
      and 70,025 unigenes significantly matched a sequence in at least one of the seven
      databases. A total of 24,060 (19.59%) unigenes can be assigned to 19 KEGG
      pathways, and 1,644 unigenes were differentially expressed between DS and CK, of
      which 519 unigenes were up-regulated and 1,125 unigenes down-regulated. Of the 47
      significantly enriched GO terms, 14, 7 and 26 items were related to BP, CC and
      MF, respectively. KEGG enrichment analysis showed 398 DEGs involved in 97
      different pathways, of which 119 DEGs were up-regulated and 279 DEGs were down
      regulated under drought stress. In addition, we found 4438 transcriptor factors
      (TFs) in sea buckthorn, of which 100 were differentially expressed between DS and
      CK. These results lay a first foundation for further investigations of the very
      specific functions of these unigenes in sea buckthorn in response to drought
      stress.

PMID- 30102737
TI  - Improvement of Mycobacterium tuberculosis detection by Xpert MTB/RIF Ultra: A
      head-to-head comparison on Xpert-negative samples.
AB  - BACKGROUND: The new Xpert MTB/RIF Ultra assay (Ultra, Cepheid, Sunnyvale, USA) is
      a cartridge-based automated diagnostic test that can simultaneously identify
      Mycobacterium tuberculosis complex (MTB) and resistance to Rifampicin (RIF). With
      respect to the previous version Xpert MTB/RIF assay (Xpert), IS6110/IS1081
      repetitive elements probes have been added allowing the detection of lower MTB
      load, defined by the new semi-quantitative category "trace" with indeterminate
      RIF resistance. The aim of this study was to evaluate performance of the new
      version Ultra on Xpert-negative, but TB culture-positive clinical samples.
      METHODS: The de-identified frozen samples (-20  degrees C) collected over a 4
      year period (February 2014-October 2017), which had previously resulted smear
      negative, Xpert-negative but MTB culture-positive, were analyzed with Ultra. The
      de-frosted samples were loaded into the cartridge using the same process as the
      previous version, according to manufacturer's instruction. RESULTS: During the
      study period 382 MTB culture-positive samples were archived: 314 resulted Xpert
      positive and 68 Xpert-negative. Thirty-one of the 68 Xpert-negative samples
      resulted positive with Ultra, with an overall improvement in MTB detection of
      45.6%. Out of 36 Xpert-negative respiratory samples, 18 resulted Ultra-positive
      with the following semi-quantitative loads: "low"(n = 1), "very low"(n = 11),
      "trace"(n = 6), with an improvement in MTB detection of 50%. The best performance
      was achieved on bronchoalveolar lavage specimens (53.8%). Out of 32 Xpert
      negative non-respiratory samples, 13 resulted Ultra-positive with the following
      semi-quantitative loads: "very low"(n = 7), "trace"(n = 6), with an improvement
      in MTB detection of 40.6%. The best performance was achieved on biopsies (55.6%)
      and lymph nodes (50%). The new category "trace" detected 12 out of the 31 Ultra
      positive MTB samples; in the remaining 19 samples RIF susceptibility was
      determined with 100% concordance with the phenotypic susceptibility test. The
      mean time to positivity of samples found negative by Ultra was significantly
      longer in comparison to positive samples in liquid culture. CONCLUSIONS: Our
      results are consistent with the few studies published so far and confirm the
      better performance of Ultra compared to the previous version in both respiratory
      and non-respiratory smear-negative samples, with an overall improvement of 45.6%.

PMID- 30102738
TI  - Correction: It's not the 'what', but the 'how': Exploring the role of debt in
      natural resource (un)sustainability.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0201141.].

PMID- 30102739
TI  - Asymptomatic fluid overload predicts survival and cardiovascular event in
      incident Chinese peritoneal dialysis patients.
AB  - BACKGROUND: Fluid overload is common among asymptomatic peritoneal dialysis (PD)
      patients. We aim to determine the prevalence and prognostic significance of fluid
      overload, as measured by bioimpedance spectroscopy, in asymptomatic incident PD
      patients. METHODS: We performed a single-center study on 311 incident PD
      patients. Volume status was represented by the volume of overhydration (OH),
      OH/extracellular water (ECW) ratio, ECW/total body water (TBW) ratio, and ECW to
      intracellular water (ICW) ratio (E:I ratio). Patient survival, technique survival
      and cardiovascular event-free survival were determined. RESULTS: The median
      period of follow up was 27.3 months. Fluid overload was present in 272 patients
      (87.5%) when defined as OH volume over 1.1L. All hydration parameters
      significantly correlated with Charlson Comorbidity Index, and inversely with
      total Kt/V, and serum albumin. Multivariate cause-specific Cox analysis showed
      that volume status independently predicted patient survival; every 0.1 unit
      increase in E:I ratio was associated with 24.5% increase in all-cause mortality
      (adjusted cause-specific hazard ratio [ACSHR] 1.245, p = 0.002). Hydration status
      was also an independent predictor of cardiovascular event-free survival after
      excluding hospital admission for congestive heart failure; each 0.1 unit increase
      in E:I ratio was associated with 18.7% decrease in cardiovascular event-free
      survival (ACSHR 1.187, p = 0.011). In contrast, hydration parameters were not
      associated with technique survival. CONCLUSIONS: Fluid overload is common in
      asymptomatic incident PD patients and is a strong predictor of patient survival
      and cardiovascular event. The impact of bioimpedance spectroscopy-guided fluid
      management on the outcome of PD patients deserves further study.

PMID- 30102741
TI  - EspH is a hypervirulence factor for Mycobacterium marinum and essential for the
      secretion of the ESX-1 substrates EspE and EspF.
AB  - The pathogen Mycobacterium tuberculosis employs a range of ESX-1 substrates to
      manipulate the host and build a successful infection. Although the importance of
      ESX-1 secretion in virulence is well established, the characterization of its
      individual components and the role of individual substrates is far from complete.
      Here, we describe the functional characterization of the Mycobacterium marinum
      accessory ESX-1 proteins EccA1, EspG1 and EspH, i.e. proteins that are neither
      substrates nor structural components. Proteomic analysis revealed that EspG1 is
      crucial for ESX-1 secretion, since all detectable ESX-1 substrates were absent
      from the cell surface and culture supernatant in an espG1 mutant. Deletion of
      eccA1 resulted in minor secretion defects, but interestingly, the severity of
      these secretion defects was dependent on the culture conditions. Finally, espH
      deletion showed a partial secretion defect; whereas several ESX-1 substrates were
      secreted in normal amounts, secretion of EsxA and EsxB was diminished and
      secretion of EspE and EspF was fully blocked. Interaction studies showed that
      EspH binds EspE and therefore could function as a specific chaperone for this
      substrate. Despite the observed differences in secretion, hemolytic activity was
      lost in all M. marinum mutants, implying that hemolytic activity is not strictly
      correlated with EsxA secretion. Surprisingly, while EspH is essential for
      successful infection of phagocytic host cells, deletion of espH resulted in a
      significantly increased virulence phenotype in zebrafish larvae, linked to poor
      granuloma formation and extracellular outgrowth. Together, these data show that
      different sets of ESX-1 substrates play different roles at various steps of the
      infection cycle of M. marinum.

PMID- 30102743
TI  - Feasibility, safety, and reliability of exercise testing using the combined arm
      leg (Cruiser) ergometer in subjects with a lower limb amputation.
AB  - BACKGROUND: Physical fitness of patients with a lower limb amputation predicts
      their walking ability and may be improved by physical exercise and training. A
      maximal exercise test is recommended prior to training in order to determine
      cardiovascular risks and design exercise programs. A potentially suitable
      ergometer for maximal exercise testing in patients with a lower limb amputation
      is the combined arm-leg (Cruiser) ergometer. The aim of this study was to
      determine feasibility, safety, and reliability of (sub)maximal exercise testing
      on the Cruiser ergometer in subjects with a lower limb amputation. METHODS AND
      FINDINGS: Subjects with a lower limb amputation performed 1 submaximal exercise
      test and 3 maximal exercise tests on the Cruiser ergometer. Feasibility was
      determined by examining whether key variables such as power output, heart rate
      and oxygen uptake were correctly and reliably measured, by determining whether a
      test was a maximal aerobic performance, by studying reasons for non-completion,
      and by measuring gross efficiency. Safety was analyzed by recording
      complications, electrocardiogram results, and blood pressure. Reliability was
      tested by comparing the results of the second and third maximal exercise test.
      Seventeen subjects (14 men and 3 women) out of 21 preselected subjects completed
      the study. In general, the maximal Cruiser exercise test was feasible. Almost 75%
      of the subjects reached a maximal aerobic performance. The test was also safe
      because no complications occurred, although electrocardiogram and blood pressure
      could only be reliably recorded in most subjects just before and after the test.
      Reliability was good: Intraclass correlation was 0.84 for peak oxygen uptake.
      CONCLUSIONS: The Cruiser ergometer is a feasible, safe, and reliable ergometer
      for measuring physical fitness of subjects with a lower limb amputation.

PMID- 30102742
TI  - A continental-wide molecular approach unraveling mtDNA diversity and geographic
      distribution of the Neotropical genus Hoplias.
AB  - With an estimate of around 9,000 species, the Neotropical region hosts the
      greatest diversity of freshwater fishes of the world. Genetic surveys have the
      potential to unravel isolated and unique lineages and may result in the
      identification of undescribed species, accelerating the cataloguing of extant
      biodiversity. In this paper, molecular diversity within the valuable and
      widespread Neotropical genus Hoplias was assessed by means of DNA Barcoding. The
      geographic coverage spanned 40 degrees of latitude from French Guiana to
      Argentina. Our analyses revealed 22 mitochondrial lineages fully supported by
      means of Barcode Index Number, Automatic Barcode Gap Discovery and phylogenetic
      analyses. This mtDNA survey revealed the existence of 15 fully supported
      mitochondrial lineages within the once considered to be the continentally
      distributed H. malabaricus. Only four of them are currently described as valid
      species however, leaving 11 mitochondrial lineages currently "masked" within this
      species complex. Mean genetic divergence was 13.1%. Barcoding gap analysis
      discriminated 20 out of the 22 lineages tested. Phylogenetic analyses showed that
      all taxonomically recognized species form monophyletic groups. Hoplias
      malabaricus sensu stricto clustered within a large clade, excluding the
      representatives of the La Plata River Basin. In the H. lacerdae group, all
      species but H. curupira showed a cohesive match between taxonomic and molecular
      identification. Two different genetic lineages were recovered for H. aimara.
      Given the unexpected hidden mitochondrial diversity within H. malabaricus, the
      COI sequence composition of specimens from Suriname (the type locality),
      identified as H. malabaricus sensu stricto, is of major importance.

PMID- 30102740
TI  - Kinetic analysis of the influenza A virus HA/NA balance reveals contribution of
      NA to virus-receptor binding and NA-dependent rolling on receptor-containing
      surfaces.
AB  - Interactions of influenza A virus (IAV) with sialic acid (SIA) receptors
      determine viral fitness and host tropism. Binding to mucus decoy receptors and
      receptors on epithelial host cells is determined by a receptor-binding
      hemagglutinin (HA), a receptor-destroying neuraminidase (NA) and a complex in
      vivo receptor-repertoire. The crucial but poorly understood dynamics of these
      multivalent virus-receptor interactions cannot be properly analyzed using
      equilibrium binding models and endpoint binding assays. In this study, the use of
      biolayer interferometric analysis revealed the virtually irreversible nature of
      IAV binding to surfaces coated with synthetic sialosides or engineered
      sialoglycoproteins in the absence of NA activity. In addition to HA, NA was shown
      to be able to contribute to the initial binding rate while catalytically active.
      Virus-receptor binding in turn contributed to receptor cleavage by NA. Multiple
      low-affinity HA-SIA interactions resulted in overall extremely high avidity but
      also permitted a dynamic binding mode, in which NA activity was driving rolling
      of virus particles over the receptor-surface. Virus dissociation only took place
      after receptor density of the complete receptor-surface was sufficiently
      decreased due to NA activity of rolling IAV particles. The results indicate that
      in vivo IAV particles, after landing on the mucus layer, reside continuously in a
      receptor-bound state while rolling through the mucus layer and over epithelial
      cell surfaces driven by the HA-NA-receptor balance. Quantitative BLI analysis
      enabled functional examination of this balance which governs this dynamic and
      motile interaction that is expected to be crucial for penetration of the mucus
      layer and subsequent infection of cells by IAV but likely also by other enveloped
      viruses carrying a receptor-destroying enzyme in addition to a receptor-binding
      protein.

PMID- 30102744
TI  - Integrating the ecophysiology and biochemical stress indicators into the paradigm
      of mangrove ecology and a rehabilitation blueprint.
AB  - The continuous degradation of mangrove habitats has encouraged governments and
      multi-lateral agencies to undertake rehabilitation initiatives to foster the
      recovery and biodiversity of these areas. However, some rehabilitation
      initiatives suffer high mortality because of incorrect species-site matching and
      failure to recognize the ecophysiology of mangrove species. This study
      investigated the effects of salinity, water depth and inundation on the growth,
      biochemical stress responses, and ecophysiology of Rhizophora stylosa in
      greenhouse conditions. Propagules were cultured in aquarium tanks and irrigated
      with low (0 ppt), moderate (20 ppt), and high (35 ppt) salinity treatments. In
      the first setup, the seedlings were cultured in aquarium tanks and arranged on
      the top of a platform at different elevations, subjecting the seedlings to
      flooding with low-water (3-5 cm), mid-water (10-13 cm) and high-water (30-33 cm)
      levels for ten months. In another setup, the seedlings were cultured for 15
      months at the low-water level and subjected to inundation hydroperiods: semi
      diurnal, diurnal and permanent inundation for one week. These microcosms
      simulated emerged and submerged conditions, mimicking intertidal inundation that
      seedlings would experience. The results showed that salinity significantly
      affected the early development of the cultured seedlings with higher growth rates
      and biomass at low and moderate salinity than those at high salinity. Levels of
      reactive oxygen species (ROS) and antioxidant activities (AOX) were significantly
      lower in the emerged condition than those in an inundated condition. Inundation
      imposed a higher-degree of stress than that of the salinity effect, with
      prolonged inundation caused sublethal damage (chlorotic leaves). Furthermore,
      inundation caused the reduction of photosynthetic pigments and fluorescence,
      dependent on salinity. Extrapolating the ecophysiology of R. stylosa, this
      species had low tolerance to inundation stress (high ROS and AOX, reduced
      pigments). Translating this low tolerance to field conditions, in the frequently
      inundated areas (i.e., seafront mangrove fringes) that are subjected to longer
      inundation at spring tides, this species may suffer from oxidative stress,
      stunted growth and consequently low survival.

PMID- 30102745
TI  - Salmonella Typhimurium effector SseI inhibits chemotaxis and increases host cell
      survival by deamidation of heterotrimeric Gi proteins.
AB  - Salmonella enterica serotype Typhimurium (S. Typhimurium) is one of the most
      frequent causes of food-borne illness in humans and usually associated with acute
      self-limiting gastroenteritis. However, in immunocompromised patients, the
      pathogen can disseminate and lead to severe systemic diseases. S. Typhimurium are
      facultative intracellular bacteria. For uptake and intracellular life, Salmonella
      translocate numerous effector proteins into host cells using two type-III
      secretion systems (T3SS), which are encoded within Salmonella pathogenicity
      islands 1 (SPI-1) and 2 (SPI-2). While SPI-1 effectors mainly promote initial
      invasion, SPI-2 effectors control intracellular survival and proliferation. Here,
      we elucidate the mode of action of Salmonella SPI-2 effector SseI, which is
      involved in control of systemic dissemination of S. Typhimurium. SseI deamidates
      a specific glutamine residue of heterotrimeric G proteins of the Galphai family,
      resulting in persistent activation of the G protein. Gi activation inhibits cAMP
      production and stimulates PI3-kinase gamma by Galphai-released Gbetagamma
      subunits, resulting in activation of survival pathways by phosphorylation of Akt
      and mTOR. Moreover, SseI-induced deamidation leads to non-polarized activation of
      Galphai and, thereby, to loss of directed migration of dendritic cells.

PMID- 30102746
TI  - Macrophage-derived LTB4 promotes abscess formation and clearance of
      Staphylococcus aureus skin infection in mice.
AB  - The early events that shape the innate immune response to restrain pathogens
      during skin infections remain elusive. Methicillin-resistant Staphylococcus
      aureus (MRSA) infection engages phagocyte chemotaxis, abscess formation, and
      microbial clearance. Upon infection, neutrophils and monocytes find a gradient of
      chemoattractants that influence both phagocyte direction and microbial clearance.
      The bioactive lipid leukotriene B4 (LTB4) is quickly (seconds to minutes)
      produced by 5-lipoxygenase (5-LO) and signals through the G protein-coupled
      receptors LTB4R1 (BLT1) or BLT2 in phagocytes and structural cells. Although it
      is known that LTB4 enhances antimicrobial effector functions in vitro, whether
      prompt LTB4 production is required for bacterial clearance and development of an
      inflammatory milieu necessary for abscess formation to restrain pathogen
      dissemination is unknown. We found that LTB4 is produced in areas near the
      abscess and BLT1 deficient mice are unable to form an abscess, elicit neutrophil
      chemotaxis, generation of neutrophil and monocyte chemokines, as well as reactive
      oxygen species-dependent bacterial clearance. We also found that an ointment
      containing LTB4 synergizes with antibiotics to eliminate MRSA potently. Here, we
      uncovered a heretofore unknown role of macrophage-derived LTB4 in orchestrating
      the chemoattractant gradient required for abscess formation, while amplifying
      antimicrobial effector functions.

PMID- 30102747
TI  - Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its
      host cell receptor ACE2.
AB  - The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein
      consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin
      converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular
      membranes through a pre- to postfusion conformation transition. Here, we report
      the structure of the SARS-CoV S glycoprotein in complex with its host cell
      receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex
      structure shows that only one receptor-binding domain of the trimeric S
      glycoprotein binds ACE2 and adopts a protruding "up" conformation. In addition,
      we studied the structures of the SARS-CoV S glycoprotein and its complexes with
      ACE2 in different in vitro conditions, which may mimic different conformational
      states of the S glycoprotein during virus entry. Disassociation of the S1-ACE2
      complex from some of the prefusion spikes was observed and characterized. We also
      characterized the rosette-like structures of the clustered SARS-CoV S2 trimers in
      the postfusion state observed on electron micrographs. Structural comparisons
      suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after
      trypsin cleavage into the S1 and S2 subunits and acidic pH treatment. However,
      binding to the receptor opens up the receptor-binding domain of S1, which could
      promote the release of the S1-ACE2 complex and S1 monomers from the prefusion
      spike and trigger the pre- to postfusion conformational transition.

PMID- 30102750
TI  - Response to the comment on "Promising blood-derived biomarkers for estimation of
      the postmortem interval".
AB  - Following Meurs and Szykula's comment on our published article titled "Promising
      blood-derived biomarkers for estimation of the postmortem interval", we recognize
      the importance of the issues raised, but we would like to emphasize that these
      contain some misinterpretations and that most of the points were already
      discussed in depth in our manuscript particularly in the conclusion section. We
      also aim to highlight further data regarding the difficulties of postmortem
      interval estimation.

PMID- 30102749
TI  - Critical appraisal of the potential role of intensity modulated proton therapy in
      the hypofractionated treatment of advanced hepatocellular carcinoma.
AB  - PURPOSE: To investigate the role of intensity modulated proton therapy (IMPT) for
      advanced hepatocellular carcinoma in comparison with volumetric modulated arc
      therapy (VMAT). METHODS: An in-silico planning study was performed on 20
      patients. The prescription dose was 60Gy in 6 fractions. Patients were planned
      with abdominal compression. IMPT plans were optimized with or without the
      inclusion of CT calibration (3%) and isocenter positioning (2,4,6mm)
      uncertainties. Plan robustness was appraised comparing rubust optimized plans vs
      standard plans and also in terms of the worst-case scenario. VMAT plans were
      optimized for 10FFF photon beams using 2 partial arcs. RESULTS: Target coverage
      was fully achieved by both VMAT and IMPT plans with a significant improvement in
      homogeneity (~25%) with IMPT. Integral dose was reduced of ~60% with IMPT while
      the conformality of the dose distributions was similar among techniques. The
      sparing of the organs at risk was strongly improved with IMPT although all
      clinical objectives were met for both techniques. The inclusion of the
      uncertainties in the optimization lead to some deterioration in the target dose
      homogeneity (from 40 to 80% worse with 4 or 6mm position uncertainty) while none
      of the coverage parameters or OAR objective was violated. The worst-case scenario
      analysis demonstrated the risk of a major target underdosage only in the case of
      the most extreme errors (6mm) with D98% in average ~12% lower than the threshold.
      CONCLUSION: IMPT with the support of abdominal compression, can be considered a
      viable solution also for advanced hepatocellular carcinoma patients. Great care
      shall be put in the minimization of the residual respiration and positioning
      uncertainties but the dosimetric advantage for organs at risk and the relative
      robustness on target coverage are promising factors.

PMID- 30102748
TI  - Seven-transmembrane receptor protein RgsP and cell wall-binding protein RgsM
      promote unipolar growth in Rhizobiales.
AB  - Members of the Rhizobiales (class of alpha-proteobacteria) display zonal
      peptidoglycan cell wall growth at one cell pole, contrasting with the dispersed
      mode of cell wall growth along the sidewalls of many other rod-shaped bacteria.
      Here we show that the seven-transmembrane receptor (7TMR) protein RgsP
      (SMc00074), together with the putative membrane-anchored peptidoglycan
      metallopeptidase RgsM (SMc02432), have key roles in unipolar peptidoglycan
      formation during growth and at mid-cell during cell division in Sinorhizobium
      meliloti. RgsP is composed of a periplasmic globular 7TMR-DISMED2 domain, a
      membrane-spanning region, and cytoplasmic PAS, GGDEF and EAL domains. The EAL
      domain confers phosphodiesterase activity towards the second messenger cyclic di
      GMP, a key regulatory player in the transition between bacterial lifestyles. RgsP
      and RgsM localize to sites of zonal cell wall synthesis at the new cell pole and
      cell divison site, suggesting a role in cell wall biogenesis. The two proteins
      are essential for cell wall biogenesis and cell growth. Cells depleted of RgsP or
      RgsM had an altered muropeptide composition and RgsM binds to peptidoglycan. RgsP
      and RgsM orthologs are functional when interchanged between alpha-rhizobial
      species pointing to a conserved mechanism for cell wall biogenesis/remodeling
      within the Rhizobiales. Overall, our findings suggest that RgsP and RgsM
      contribute to the regulation of unipolar cell wall biogenesis in alpha-rhizobia.

PMID- 30102752
TI  - Music and Brain Development.
AB  - When I was young, I remember my parents used to play the Beatles song "Here Comes
      the Sun" in the morning on the old record player. My mother helped hire the first
      band director at my middle school, and my father played opera in the car on my
      way to elementary school. I dabbled with different instruments, and played
      trumpet (cornet actually), flute, piccolo, oboe, English horn, and Ukulele. I
      also sang in several choirs and still sing today. What did all this musical
      influence do to my developing brain? This article reviews some of the existing
      evidence about music and brain development, to make a case for exposing children
      to music at an early age and supporting school music programs. [Pediatr Ann.
      2018;47(8):e306-e308.].

PMID- 30102753
TI  - Pediatric Mental Health Disorders.

PMID- 30102754
TI  - Update on Common Psychiatric Medications for Children.
AB  - For children and adolescents with uncomplicated psychiatric disorders,
      pediatricians are often the first prescriber of psychiatric medications. Mental
      health disorders commonly treated by pediatricians include attention
      deficit/hyperactivity disorder (ADHD), depression, and anxiety. There are several
      safe and effective first-line medications for these disorders. For ADHD,
      stimulants and nonstimulants can be used as first-line interventions. For anxiety
      and depression, selective serotonin reuptake inhibitors are well-established
      treatments and often well-tolerated. With appropriate support and training,
      pediatricians can increase access for children to necessary mental health
      treatments. [Pediatr Ann. 2018;47(8):e311-e316.].

PMID- 30102755
TI  - Starting Early: Promoting Emotional and Behavioral Well-Being in Infant and
      Toddler Well-Child Care.
AB  - A child's experiences during the first 3 years of life can have a profound impact
      on mental health outcomes later in childhood and across the lifespan. Safe and
      effective therapies for mental health concerns in early childhood exist, but
      access to them is limited. Pediatricians have a unique opportunity to identify
      risk and resilience factors and support healthy emotional, behavioral, and social
      development during infancy and toddlerhood. This article presents a
      developmentally focused approach to integrating the growing science of early
      childhood social-emotional development into primary care practice, providing both
      empiric and practical rationales. [Pediatr Ann. 2018;47(8):e317-e322.].

PMID- 30102756
TI  - Behavioral Health Care for Children Who Are Medically Hospitalized.
AB  - Youth admitted to pediatric hospitals face a variety of emotional challenges
      throughout their stay. In addition to feeling compromised by their acute medical
      condition, managing the requirements imposed by hospital care can intensify the
      potential for behavioral dysregulation. Even meeting basic behavioral
      expectations often requires children to be highly vulnerable, uncomfortable, and
      in pain, having to trust a parade of people routinely delivering aversive
      interventions, all in the context of overwhelmed caregivers. Behavioral medicine
      approaches are thus essential for supporting adaptive coping to optimize
      emotional and pathophysiological recovery. Clinical implementation requires
      integration of emotional and behavioral health initiatives into medical services
      across the broadest of disciplines with hospital-wide vigilance to safety risks.
      Providers can support behavioral resiliency by nurturing youth who are
      hospitalized to become increasingly active agents in their care while bolstering
      the consistency of their behavioral expectations through effective communication
      and an empathic treatment approach tailored to their socioemotional needs.
      [Pediatr Ann. 2018;47(8):e323-e327.].

PMID- 30102757
TI  - Evaluation and Management of Psychiatric Emergencies in Children.
AB  - Mental illness among children and adolescents is an increasing burden, projected
      to become one of the world's leading disabilities in near future. A dearth of
      specialized services and personnel to provide optimal care affects the disease
      burden, prevalence, health care services, and health care costs. The increasing
      demand weighs down on generalized systems of care such as emergency department
      (ED) services, in which the lack of specific training, personnel, and specialized
      protocols tends to prolong length of stay, recidivism, and suboptimal care. This
      article reviews outcomes and trends of overburdened ED systems in the context of
      pediatric mental health care management, guidelines of care, and strategies to
      manage common pediatric mental health emergencies and expand services within the
      ED. [Pediatr Ann. 2018;47(8):e328-e333.].

PMID- 30102758
TI  - Refusal of Vitamin K Injection: Survey of the Current Literature and Practical
      Tips for Pediatricians.
AB  - Vitamin K refusal and associated sequelae of vitamin K deficiency bleed (VKDB) in
      the newborn period is becoming a more common occurrence. We present six recent
      cases from a 4-month period in 2017 of parent refusal of vitamin K and describe
      the reasons for refusal and the clinical outcomes of these infants. There have
      been a number of case reports citing the rising incidence of VKDB and the reasons
      why parents refuse. However, there is a gap in the literature and clinical
      practice guidelines describing how a physician should approach a refusal in the
      hospital and in the office, and the need to report a refusal to child welfare. In
      addition, we describe a scenario in which the caregivers provide a religious
      reason for refusal of vitamin K that, to the best of our knowledge, has yet to be
      cited in the literature. [Pediatr Ann. 2018;47(8):e334-e338.].

PMID- 30102759
TI  - Orexins increase the firing activity of nigral dopaminergic neurons and
      participate in motor control in rats.
AB  - Orexin is a member of neuropeptides which is involved in the central motor
      control. The substantia nigra pars compacta (SNc) is an important nucleus
      participating in motor control under both physiological and pathological
      conditions. Morphological studies reveal that orexinergic neurons located in
      lateral hypothalamus innervate the SNc. Both orexin-1 receptors (OX1 R) and
      orexin-2 receptors (OX2 R) are expressed in the SNc. To investigate the effects
      of orexins on SNc, single unit in vivo extracellular recordings and behavioral
      tests were performed in this study. Micro-pressure administration of orexin A and
      orexin B significantly increased the spontaneous firing rate of nigral DAergic
      neurons by 65.87 +/- 7.73% and 90.49 +/- 17.83%, respectively. The excitatory
      effects of orexin A on nigral DAergic neurons were mainly mediated by OX1 R,
      while OX2 R were involved in the increase in firing rate induced by orexin B.
      Selectively blocking OX1 R and OX2 R significantly decreased the firing rate of
      nigral DAergic neurons by 36.77 +/- 6.26% and 32.04 +/- 6.12%, respectively,
      which suggested that endogenous orexins modulated the spontaneous firing activity
      of nigral DAergic neurons. Finally, both elevated body swing test and haloperidol
      induced postural behavioral test showed that unilateral microinjection of orexin
      A and orexin B induced significantly contralateral-biased swing and deflection
      behavior. Meanwhile, the specific OX1 R and OX2 R antagonists produced opposite
      effects. The present electrophysiological and behavioral studies suggested that
      orexins increased the firing activity of nigral DAergic neurons and participated
      in central motor control. Open Practices Open Science: This manuscript was
      awarded with the Open Materials Badge. For more information see:
      https://cos.io/our-services/open-science-badges/.

PMID- 30102760
TI  - A Reliable Regression-Based Approach for Reassociating Human Skeletal Elements of
      the Lower Limbs from Commingled Assemblages.
AB  - Accurate sorting of commingled human remains comprises a fundamental requirement
      for all further anthropological analyses. The lower limb bones are particularly
      important for reconstructing biological profiles. This study introduces a metric
      technique for sorting these elements using eight standard anthropological
      measurements and 222 adult individuals from Greece. The bones utilized were the
      os coxae, the femora, the tibiae and the tali. Simple regression analyses were
      used to develop functions for reassociating articulating bones, providing strong
      correlations (r = 0.74-0.95, p-value <0.05) and high coefficients of
      determination (r2 =0.54-0.91). Blind tests demonstrated that combining metric and
      morphoscopic techniques provides an excellent sorting accuracy for the hip and
      knee joints (ten of ten individuals), allowing for a reliable reassociation
      between a sex and age indicator (os coxae) and a body size indicator (femur).
      Overall, these results indicate the high value of metric methods in sorting
      commingled human remains.

PMID- 30102761
TI  - Regulation of Melanopsin Signaling: Key Interactions of the Nonvisual
      Photopigment.
AB  - Melanopsin is a G protein-coupled receptor with a peak sensitivity in the blue
      part of the spectrum, which plays a key role in nonvisual light-mediated
      signaling. Recently, its importance in forming visual pathway as well as its role
      in blood vessels photorelaxation was also revealed. Melanopsin was discovered in
      1998 in Xenopus leavis. Since then, the melanopsin presence was demonstrated
      across the species. The existence of two melanopsin genes (opn4m and opn4x) as
      well as melanopsin isoforms resulting from alternative splicing contributes to
      the variety in melanopsin-regulated processes. In this review, the diversity in
      melanopsin-induced signaling, regulation of melanopsin activity by
      phosphorylation and regulation of melanopsin mRNA are discussed.

PMID- 30102764
TI  - The use of a surface active agent in the protection of a fusion protein during
      bioprocessing.
AB  - The bioprocessing of a fusion protein is characterised by low yields and at a
      series of recovery and purification stages that leads to an overall 90% loss.
      Much of this apparent loss is due to the denaturation of a protein, missing a
      vital affinity ligand. However, there is evidence of the protection of
      degradation products which occurs in the presence of shear plus air/liquid
      interfaces. This study seeks out to characterise the loss and use ultra-scale
      down studies to predict its occurrence and hence shows these may be diminished by
      the use of protective reagents such as Pluronic F68.

PMID- 30102762
TI  - Sex Differences in Photic Entrainment and Sensitivity to Ethanol-Induced
      Chronodisruption in Adult Mice After Adolescent Intermittent Ethanol Exposure.
AB  - BACKGROUND: Evidence supports a role for the circadian system in alcohol use
      disorders, but the impact of adolescent alcohol exposure on circadian timing
      later in life is unknown. Acute ethanol (EtOH) attenuates circadian photic phase
      resetting in adult, but not adolescent, rodents. However, nearly all studies have
      focused on males and it is unknown whether this adolescent-typical insensitivity
      to EtOH persists into adulthood after adolescent drinking. METHODS: Circadian
      activity was monitored in C57BL/6J mice receiving adolescent intermittent EtOH
      (AIE) exposure (15% EtOH and water every other day throughout adolescence) or
      water alone followed by 24 days wherein EtOH was not available (washout). Mice
      then received a challenge dose of EtOH (1.5 g/kg, intraperitoneal) or saline 15
      minutes prior to a 30-minute phase-delaying light pulse and then were released
      into constant darkness (DD). To control for possible phase-shifting by EtOH
      challenge alone, a separate group of mice underwent AIE exposure (or water-only)
      and washout and then received an EtOH or saline injection, but did not receive a
      light pulse prior to DD. RESULTS: Striking sex differences in nearly all measures
      of circadian photic entrainment were observed during adolescence but AIE effects
      were subtle and few. Only EtOH-naive adult male mice showed attenuated photic
      phase-shifts with EtOH challenge, while all other groups showed normal phase
      resetting responses to light. AIE-exposed females showed a persistent delay in
      activity offset. CONCLUSIONS: Adult male AIE-exposed mice retained adolescent
      like insensitivity to EtOH-induced suppression of photic phase-resetting,
      suggesting AIE-induced "lock-in" of an adolescent behavioral phenotype. Adult AIE
      exposed females showed delayed initiation of the rest phase. Our results also
      indicate that intermittent EtOH drinking has subtle effects on circadian activity
      in mice during adolescence that differ from previously reported effects on adult
      males. The observed sex differences in circadian activity, EtOH consumption and
      preference, and responses to EtOH challenge merit future mechanistic study.

PMID- 30102763
TI  - Epitope-specific affinity maturation improved stability of potent protease
      inhibitory antibodies.
AB  - Targeting effectual epitopes is essential for therapeutic antibodies to
      accomplish their desired biological functions. This study developed a competitive
      dual color fluorescence-activated cell sorting (FACS) to maturate a matrix
      metalloprotease 14 (MMP-14) inhibitory antibody. Epitope-specific screening was
      achieved by selection on MMP-14 during competition with N-terminal domain of
      tissue inhibitor of metalloproteinase-2 (TIMP-2) (nTIMP-2), a native inhibitor of
      MMP-14 binding strongly to its catalytic cleft. 3A2 variants with high potency,
      selectivity, and improved affinity and proteolytic stability were isolated from a
      random mutagenesis library. Binding kinetics indicated that the affinity
      improvements were mainly from slower dissociation rates. In vitro degradation
      tests suggested the isolated variants had half lives 6-11-fold longer than the
      wt. Inhibition kinetics suggested they were competitive inhibitors which showed
      excellent selectivity toward MMP-14 over highly homologous MMP-9. Alanine
      scanning revealed that they bound to the vicinity of MMP-14 catalytic cleft
      especially residues F204 and F260, suggesting that the desired epitope was
      maintained during maturation. When converted to immunoglobulin G, B3 showed 5.0
      nM binding affinity and 6.5 nM inhibition potency with in vivo half-life of 4.6
      days in mice. In addition to protease inhibitory antibodies, the competitive FACS
      described here can be applied for discovery and engineering biosimilars, and in
      general for other circumstances where epitope-specific modulation is needed.

PMID- 30102765
TI  - Evaluation of oral microbial corrosion on the surface degradation of dental
      implant materials.
AB  - BACKGROUND: Titanium (Ti) dominates as the material of choice for dental implant
      systems. Recently, titanium-zirconium alloy (TiZr) and zirconia (ZrO2 ) have
      emerged as alternative materials due to higher mechanical strength and lower
      corrosion susceptibility. Oral pathogenic bacteria can colonize Ti surfaces,
      leading to surface degradation, which has yet to be investigated on TiZr and ZrO2
      . The aim of this study was to compare in vitro oral bacterial adhesion and
      subsequent surface degradation on commercial Ti, TiZr, and ZrO2 implants.
      METHODS: Ti, TiZr, and ZrO2 implants with sandblasted, acid-etched (SLA) surfaces
      in addition to modified SLA-treated (modSLA) Ti implants (n = 3) were immersed
      for 30 consecutive days in Streptococcus polyculture. Post-immersion, adherent
      bacterial count was quantified. Optical microscopy was used to assess qualitative
      degradation and score Ti-based implants based on degree of surface damage while
      electrochemical testing quantified corrosion behavior. Analysis of variance
      followed by post-hoc Tukey test was used to statistically compare quantitative
      results (alpha = 0.05). RESULTS: Ti-SLA, Ti-modSLA, and TiZr-SLA implants
      exhibited localized features characteristic of corrosion attack while ZrO2 -SLA
      implants experienced minimal changes in surface morphology as compared to non
      immersed control. Corrosion features were more numerous on Ti-modSLA implants but
      smaller in size as compared with those on Ti-SLA and TiZr-SLA implants. No
      significant differences in corrosion resistance (polarization resistance and
      corrosion rate) were observed between Ti-SLA, Ti-modSLA, and TiZr-SLA implants.
      CONCLUSION: TiZr and ZrO2 dental implant surfaces were not more susceptible to
      colonization and surface degradation by oral Streptococcus species than
      commercially pure Ti implants.

PMID- 30102766
TI  - Tetracycline Removal Under Solar Illumination Over Ag3 VO4 /mpg-C3 N4
      Heterojunction Photocatalysts.
AB  - Ag3 VO4 /mpg-C3 N4 (mesoporous graphitic carbon nitride) heterojunction
      photocatalysts were prepared by anchoring tiny Ag3 VO4 particles on the nanosheet
      of mpg-C3 N4 . The prepared Ag3 VO4 /mpg-C3 N4 heterojunctions were used to
      remove tetracycline (TC), a kind of antibiotics widely released into the aquatic
      environment under solar irradiation. Compared with pure mpg-C3 N4 and Ag3 VO4 ,
      Ag3 VO4 /mpg-C3 N4 displayed much higher photocatalytic activity (83.2% removal
      rate within 90 min under visible-light irradiation). Importantly, no apparent
      deactivation was observed for Ag3 VO4 /mpg-C3 N4 -40 after five cycles, inferring
      a good reusability. As confirmed by photocurrent measurement and
      photoluminescence spectra, the excellent photocatalytic property of Ag3 VO4 /mpg
      C3 N4 was credit to the electron-hole separation enhancement at the formed
      heterojunction of two semiconductors. In addition, a possible mechanism and
      intermediate products for the Ag3 VO4 /mpg-C3 N4 photocatalysts toward the
      photodegradation of TC in aqueous solution under artificial sunlight radiation
      were proposed based on the scavengers trapping test, ESR spectra and a high
      performance liquid chromatography (HPLC) coupled with mass spectrometer (MS)
      analysis. This investigation provides a low cost, green and easily practical
      approach to remove the antibiotics in the aquatic environment.

PMID- 30102767
TI  - Association between time since quitting smoking and periodontitis in former
      smokers in the national health and nutrition examination surveys (NHANES) 2009 to
      2012.
AB  - BACKGROUND: The aims of this study were to analyze the periodontal conditions
      among non-smokers, former smokers and current smokers in the two National Health
      and Nutrition Examination Surveys (NHANES) acquired between 2009 to 2012 and
      determine the association between time since quitting smoking and periodontal
      status. METHODS: Smoking status and periodontal examination data from NHANES 2009
      to 2010 and 2011 to 2012 were analyzed. Respondents included in the analysis were
      aged >=18 years, had undergone a complete NHANES Oral Health - Periodontal Exam
      with all measurements recorded as required for the periodontal classification
      algorithm, and had complete data from the NHANES Smoking - Cigarette Use
      questionnaire. Logistic regression was conducted with time since quitting as the
      exposure and presence of periodontitis as the outcome, and included adjustment
      for confounders. RESULTS: Smoking status was significantly associated with
      periodontal status (Chi-square; P < 0.0001). The rate of periodontitis was
      highest among smokers (35%), compared with former smokers (19%) and never smokers
      (13%). Among former smokers, after adjusting for confounders, each additional
      year since quitting smoking was associated with a significant reduction in the
      odds ratio (OR) for periodontitis by 3.9% (OR for each year 0.961, 95% confidence
      interval 0.948 to 0.975). CONCLUSIONS: Among former smokers, a longer time since
      quitting smoking was associated with a lower likelihood of periodontitis.
      Consequently, dental practitioners have a public health mandate to help their
      patients quit smoking. Future research should determine the best strategies for
      facilitating smoking cessation in dental patients.

PMID- 30102768
TI  - Neoplastic transformation of peribiliary stem cell niche in cholangiocarcinoma
      arisen in primary sclerosing cholangitis.
AB  - : Primary sclerosing cholangitis (PSC) is a chronic inflammatory cholangiopathy
      frequently complicated by cholangiocarcinoma (CCA). Massive proliferation of
      biliary tree stem/progenitor cells (BTSCs), expansion of peribiliary glands
      (PBGs), and dysplasia were observed in PSC. The aims of the present study were to
      evaluate the involvement of PBGs and BTSCs in CCA which emerged in PSC patients.
      Specimens from normal liver (N=5), PSC (N=20), and PSC-associated CCA (N=20) were
      included. Samples were processed for histology, immunohistochemistry and
      immunofluorescence. In vitro experiments were performed on human BTSCs, human
      mucinous primary CCA cell cultures, and human cholangiocyte cell lines (H69). Our
      results indicated that all CCAs emerging in PSC patients were mucin-producing
      tumors characterized by PBG involvement and a high expression of stem/progenitor
      cell markers. Ducts with neoplastic lesions showed higher inflammation, wall
      thickness, and PBG activation compared to non-neoplastic PSC-affected ducts. CCA
      showed higher microvascular density and higher expressions of nuclear factor
      kappaB, interleukin-6, interleukin-8, transforming growth factor beta, and
      vascular endothelial growth factor-1, compared to non-neoplastic ducts. CCA cells
      were characterized by a higher expression of epithelial-to-mesenchymal transition
      (EMT) traits and by the absence of primary cilia compared to bile ducts and PBG
      cells in controls and PSC. Our in vitro study demonstrated that
      lipopolysaccharide and oxysterols (PSC-related stressors) induced the expression
      of EMT traits, nuclear factor-kappaB pathway, autophagy, and the loss of primary
      cilia in human BTSCs. CONCLUSION: CCA arising in PSC patients is characterized by
      extensive PBG involvement and by the activation of the BTSC niche. In these
      patients, the presence of duct lesions at different stages suggests a progressive
      tumorigenesis. This article is protected by copyright. All rights reserved.

PMID- 30102769
TI  - Chiral Inductions in Excited State Reactions: Photodimerization of Alkyl 2
      Naphthoates as a Model.
AB  - Enantioselectivity in organic transformations continues to be a topic major
      interest in organic photochemistry. In the last decade, synergistic combination
      of photocatalysis and organocatalysis has emerged as a powerful strategy to gain
      enantioselectivity in photochemical reactions, and remarkable achievements have
      been obtained. In this strategy, the asymmetric induction is provided in ground
      state. In contrast, in the conventional enantioselective photochemistry, the
      chiral induction is controlled in electronic excited state, and to achieve high
      stereoselectivity is still a formidable challenge. Because the reactions of
      excited states often yield strained products with unique structures in single
      step that are difficult to form by thermal reactions, the development of new
      strategies attempted to achieve enantioselectivity in excited state reactions is
      still highly desired. Since the short excited state lifetime and low activation
      energy for reaction in excited state leave little room for manipulating the
      chiral induction, in order to gain enantioselectivity the substrate molecule has
      to already reside in a chiral environment during the excitation step. Chiral
      auxiliaries and chiral supramolecular hosts can provide such environments. In
      this presentation, we summarize the studies employing chiral auxiliary and chiral
      microreactor approaches to achieve high asymmetric inductions in excited state
      reactions performed in our laboratory. We chose the photodimerization of alkyl 2
      naphthoates as a reaction model to give deeper insights into the basic factors
      controlling chiral induction in excited state.

PMID- 30102770
TI  - Reconstruction of tricarboxylic acid cycle in Corynebacterium glutamicum with a
      genome-scale metabolic network model for trans-4-hydroxyproline production.
AB  - trans-4-Hydroxy- l-proline (Hyp) is an abundant component of mammalian collagen
      and functions as a chiral synthon for the syntheses of anti-inflammatory drugs in
      the pharmaceutical industry. Proline 4-hydroxylase (P4H) can catalyze the
      conversion of l-proline to Hyp; however, it is still challenging for the
      fermentative production of Hyp from glucose using P4H due to the low yield and
      productivity. Here, we report the metabolic engineering of Corynebacterium
      glutamicum for the fermentative production of Hyp by reconstructing tricarboxylic
      acid (TCA) cycle together with heterologously expressing the p4h gene from
      Dactylosporangium sp. strain RH1. In silico model-based simulation showed that
      alpha-ketoglutarate was redirected from the TCA cycle toward Hyp synthetic
      pathway driven by P4H when the carbon flux from succinyl-CoA to succinate
      descended to zero. The interruption of the TCA cycle by the deletion of sucCD
      encoding the succinyl-CoA synthetase (SUCOAS) led to a 60% increase in Hyp
      production and had no obvious impact on the growth rate. Fine-tuning of plasmid
      borne ProB* and P4H abundances led to a significant increase in the yield of Hyp
      on glucose. The final engineered Hyp-7 strain produced up to 21.72 g/L Hyp with a
      yield of 0.27 mol/mol (Hyp/glucose) and a volumetric productivity of 0.36 g.L -1
      .hr -1 in the shake flask fermentation. To our knowledge, this is the highest
      yield and productivity achieved by microbial fermentation in a glucose-minimal
      medium for Hyp production. This strategy provides new insights into engineering
      C. glutamicum by flux coupling for the fermentative production of Hyp and related
      products.

PMID- 30102771
TI  - Rapid identification of antimicrometastases drugs using integrated model systems
      with two dimensional monolayer, three dimensional spheroids, and zebrafish
      xenotransplantation tumors.
AB  - Treating systemic metastases at the micrometastatic stage is a potential strategy
      to inhibit cancer metastasis. This study aims to establish an apoptosis sensor
      based platform for rapid, effective, and noninvasive identification of drugs that
      can inhibit the proliferation of micrometastatic cancer cells. We stably
      transfected the plasmid DNA encoding the fluorescence resonance energy transfer
      based caspase-3 sensor into highly metastatic melanoma B16F10 cells. The
      resulting B16F10-C3 cells were applied for screening of antiproliferative and
      proapoptotic drugs in two-dimensional (2D) monolayer, three-dimensional (3D)
      spheroids, and zebrafish xenotransplantation tumors. All studies were conducted
      in 96-well plates in a high throughput manner. Fourteen compounds including six
      chemotherapeutic drugs and eight kinase inhibitors were tested. Thirteen
      compounds failed the tests due to: Drug resistance, low efficacy, poor
      pharmacokinetic profile, and/or high side effects to zebrafish. The only compound
      that passed all tests was pan-phosphatidylinositol 3-kinase (PI3K) inhibitor
      LY294002, which inhibited the proliferation of B16F10-C3 cells in both 2D and 3D
      cultures. More important, it significantly reduced the xenograft tumor size in
      zebrafish by decreasing the viability of metastatic cancer cells. Our study
      suggests that the PI3K/AKT pathway is a potential therapeutic target for the
      reactivation of tumor dormancy and proliferation of micrometastases. Moreover,
      this integrated approach is effective for rapid identification of systemic
      antimetastases drugs.

PMID- 30102772
TI  - Macrophage-specific HIF-1alpha contributes to impaired autophagic flux in non
      alcoholic steatohepatitis.
AB  - : Inflammatory cell activation drives diverse cellular programming during hepatic
      diseases. Hypoxia-inducible factors (HIFs) have recently been identified as
      important regulators of immunity and inflammation. In non-alcoholic
      steatohepatitis (NASH), HIF-1alpha is upregulated in hepatocytes where it induces
      steatosis; however, the role of HIF-1alpha in macrophages under metabolic stress
      has not been explored. In this study, we found increased HIF-1alpha levels in
      hepatic macrophages in methionine-choline-deficient (MCD) diet-fed mice and in
      macrophages of NASH patients compared to controls. The HIF-1alpha increase was
      concomitant with elevated levels of autophagy markers BNIP3, Beclin-1, LC3-II,
      and p62 both in mouse and human macrophages. LysMCre -HIFdPA fl/fl mice, which
      have HIF-1alpha levels stabilized in macrophages, showed higher steatosis and
      liver inflammation compared to HIFdPA fl/fl mice on MCD diet. In vitro and ex
      vivo experiments reveal that saturated fatty acid, palmitic acid (PA), induces
      both HIF-1alpha and impairs autophagic flux in macrophages. Using siRNA-mediated
      knock-down and over-expression of HIF-1alpha in macrophages, we demonstrated that
      PA impairs autophagy via HIF-1alpha. We found that HIF-1alpha mediates NF-kappaB
      activation and MCP-1 production and that HIF-1alpha mediated impairment of
      macrophage autophagy increases IL-1beta production contributing to MCD diet
      induced NASH. CONCLUSIONS: Palmitic acid impairs autophagy via HIF-1alpha
      activation in macrophages. HIF-1alpha and impaired autophagy are present in NASH
      in vivo in mouse macrophages and in human blood monocytes. We identified that HIF
      1alpha activation and decreased autophagic flux stimulate inflammation in
      macrophages through upregulation of NF-kappaB activation. These results suggest
      that macrophage activation in NASH involves a complex interplay between HIF
      1alpha and autophagy as these pathways promote proinflammatory overactivation in
      MCD diet-induced NASH. This article is protected by copyright. All rights
      reserved.

PMID- 30102773
TI  - Measuring blood velocity using 4D-DSA: A feasibility study.
AB  - PURPOSE: Four-dimensional (4D) DSA reconstruction provides three-dimensional (3D)
      time-resolved visualization of contrast bolus passage through arterial
      vasculature in the interventional setting. The purpose of this study was to
      evaluate the feasibility of using these data in measuring blood velocity and
      flow. METHODS: The pulsatile signals in the time concentration curves (TCCs)
      measured at different points along a vessel are markers of the movement of a
      contrast bolus and thus of blood flow. When combined with the spatial content,
      that is, geometry of the vasculature, this information then provides the data
      required to determine blood velocity. A Fourier-based algorithm was used to
      identify and follow the pulsatility signal. A Side Band Ratio (SBR) metric was
      used to reduce uncertainty in identifying the pulsatility in regions where the
      signal was weak. We tested this method using 4D-DSA reconstructions from vascular
      phantoms as well as from human studies. RESULTS: In five studies using 3D printed
      patient-specific cerebrovascular phantoms, velocities calculated from the 4D-DSAs
      were found to be within 10% of velocities measured with a flow meter. Calculated
      velocity and flow values from three human studies were within the range of those
      reported in the literature. CONCLUSIONS: 4D-DSA provides temporal and spatial
      information about blood flow and vascular geometry. This information is obtained
      using conventional rotational angiographic systems. In this small feasibility
      study, these data allowed calculations of velocity values that correlated well
      with measured values. The availability of velocity and blood flow information in
      the interventional setting would support a more quantitative approach to
      diagnosis, treatment planning and post-treatment evaluations of a variety of
      cerebrovascular diseases.

PMID- 30102774
TI  - Effects and Mechanism of Nicotinamide Against UVA- and/or UVB-mediated DNA
      Damages in Normal Melanocytes.
AB  - Melanoma incidences are increasing rapidly, and ultraviolet (UV) radiation from
      the sun is believed to be its major contributing factor. UV exposure causes DNA
      damage in skin which may initiate cutaneous skin cancers including melanoma.
      Melanoma arises from melanocytes, the melanin-producing skin cells, following
      genetic dysregulations resulting into hyperproliferative phenotype and neoplastic
      transformation. Both UVA and UVB exposures to the skin are believed to trigger
      melanocytic hyperplasia and melanomagenesis. Melanocytes by themselves are
      deficient in repair of oxidative DNA damage and UV-induced photoproducts.
      Nicotinamide, an active form of vitamin B3 and a critical component of the human
      body's defense system has been shown to prevent certain cancers including
      nonmelanoma skin cancers. However, the mechanism of nicotinamide's protective
      effects is not well understood. Here, we investigated potential protective
      effects and mechanism of nicotinamide against UVA- and/or UVB- induced damage in
      normal human epidermal melanocytes. Our data demonstrated an appreciable
      protective effect of nicotinamide against UVA- and/or UVB- induced DNA damage in
      melanocytes by decreasing both cyclobutane pyrimidine dimers and 8-hydroxy-2'
      deoxyguanosine levels. We found that the photoprotective response of nicotinamide
      was associated with the activation of nucleotide excision repair genes and NRF2
      signaling. Further studies are needed to validate our findings in in vivo models.

PMID- 30102775
TI  - High-throughput combinatorial screening reveals interactions between signaling
      molecules that regulate adult neural stem cell fate.
AB  - Advancing our knowledge of how neural stem cell (NSC) behavior in the adult
      hippocampus is regulated has implications for elucidating basic mechanisms of
      learning and memory as well as for neurodegenerative disease therapy. To date,
      numerous biochemical cues from the endogenous hippocampal NSC niche have been
      identified as modulators of NSC quiescence, proliferation, and differentiation;
      however, the complex repertoire of signaling factors within stem cell niches
      raises the question of how cues act in combination with one another to influence
      NSC physiology. To help overcome experimental bottlenecks in studying this
      question, we adapted a high-throughput microculture system, with over 500
      distinct microenvironments, to conduct a systematic combinatorial screen of key
      signaling cues and collect high-content phenotype data on endpoint NSC
      populations. This novel application of the platform consumed only 0.2% of reagent
      volumes used in conventional 96-well plates, and resulted in the discovery of
      numerous statistically significant interactions among key endogenous signals.
      Antagonistic relationships between fibroblast growth factor 2, transforming
      growth factor beta (TGF-beta), and Wnt-3a were found to impact NSC proliferation
      and differentiation, whereas a synergistic relationship between Wnt-3a and Ephrin
      B2 on neuronal differentiation and maturation was found. Furthermore, TGF-beta
      and bone morphogenetic protein 4 combined with Wnt-3a and Ephrin-B2 resulted in a
      coordinated effect on neuronal differentiation and maturation. Overall, this
      study offers candidates for further elucidation of significant mechanisms guiding
      NSC fate choice and contributes strategies for enhancing control over stem cell
      based therapies for neurodegenerative diseases.

PMID- 30102776
TI  - Hepatitis C virus manipulates humans as its favorite host for long term
      relationship.
AB  - Chronic hepatitis C virus (HCV) infection associated liver disease is a global
      health problem. HCV often causes silent disease, and eventually progresses to end
      stage liver disease. HCV infects hepatocytes, however initial manifestation of
      liver disease is mostly displayed in hepatic stellate cells causing
      fibrosis/cirrhosis, and believed to be occurring from inflammation in the liver.
      It is still unclear why HCV is not spontaneously cleared from infected liver in
      the majority of individuals and develops chronic infection with progressive liver
      disease. Direct-acting antivirals (DAAs) show excellent results in controlling
      viremia, although beneficial consequence in advanced liver disease remains to be
      understood. In this review, we highlight the current knowledge that has
      contributed in our understanding on the role of HCV in inflammation, immune
      evasion, metabolic disorders, liver pathogeneses, and efforts in vaccine
      development. This article is protected by copyright. All rights reserved.

PMID- 30102778
TI  - Characteristics of immune response to tumor-associated antigens and immune cell
      profile in hepatocellular carcinoma patients.
AB  - : Host antitumor immune responses may be different between hepatocellular
      carcinoma (HCC) caused by metabolic disorders and HCC associated with hepatitis
      virus infection. In this study, we examined the immune response of tumor
      associated antigen (TAA)-specific T cells and immune cell profile in HCC patients
      separated by cause. Thirty two patients with HBV-related HCC, 42 patients with
      HCV-related HCC, and 18 patients with non-alcoholic steatohepatitis (NASH)
      related HCC were analyzed. The frequencies of TAA-specific T cells, the
      expression levels of surface markers on each immune cell and the expression of
      each TAA in HCC tissue were measured. The immune response to TAA and immune cell
      profile were markedly different among the 3 groups. The immune response to TAA in
      the NASH-related HCC group was weaker than the responses in the other 2 groups.
      In the NASH-related HCC patients, the frequencies of effector regulatory T cells
      (eTregs) and CD8+ T cells strongly expressing cytotoxic T-lymphocyte antigen
      (CTLA)-4 were high. The frequency of CD8+ T cells strongly expressing programmed
      cell death (PD)-1 was the highest in the HBV-related HCC patients. Among these
      immune cell profiles, the frequencies of C-X-C motif chemokine receptor (CXCR)3+
      eTregs and CTLA-4+CD8+ T cells were inversely correlated with the strength of the
      TAA-specific T cell immune response, and the restoration of TAA-specific T cell
      responses by anti-CTLA-4 antibody was observed. CONCLUSION: The immune response
      to TAA were markedly different among the 3 groups, and a correlation with the
      immune cell profile was observed, suggesting that development of immunotherapy
      based on the etiology of HCC may lead to more effective treatment outcomes. This
      article is protected by copyright. All rights reserved.

PMID- 30102777
TI  - Social anxiety and eating disorder comorbidity and underlying vulnerabilities:
      Using network analysis to conceptualize comorbidity.
AB  - OBJECTIVE: Eating disorders (EDs) and social anxiety disorder (SAD) are highly co
      occurring. This comorbidity is extremely relevant, given that individuals with
      comorbid ED-SAD are less likely to seek and/or benefit from ED treatment. METHOD:
      We used network analysis to conceptualize ED-SAD comorbidity in a sample of 2,215
      participants with a primary diagnosis of ED, SAD, or no known diagnosis. We used
      novel network analyses methods to select symptoms for our models, identify
      potential illness pathways (i.e., bridge symptoms) between disorders and
      underlying vulnerabilities (e.g., perfectionism, social appearance anxiety), and
      to compare across sample types (e.g., clinical vs. nonclinical). We also tested
      several novel network analyses methods aimed at the following methodological
      concerns: (a) topological concerns (i.e., which items should be included in NA
      models), (b) how to use empirical indices to quantify bridge symptoms and (c)
      what differences in networks across samples mean. RESULTS: We found that
      difficulty with drinking beverages and eating in public were bridge symptoms
      between ED and SAD. We also found that feeling nervous about one's appearance was
      a bridge symptom. CONCLUSIONS: We identified public eating and drinking as bridge
      symptoms between EDs and SAD. Future research is needed to test if interventions
      focused on public eating and drinking might decrease symptoms of both EDs and
      SAD. Researchers can use this study (code provided) as an exemplar for how to use
      network analysis, as well as to use network analysis to conceptualize ED
      comorbidity and compare network structure and density across samples.

PMID- 30102779
TI  - Spinalization and locomotor training differentially affect muscarinic
      acetylcholine receptor type 2 abutting on alpha-motoneurons innervating the ankle
      extensor and flexor muscles.
AB  - Complete thoracic spinal cord transection (SCT) impairs excitatory cholinergic
      inputs to ankle extensor (soleus; Sol) but not to flexor (tibialis anterior; TA)
      alpha-motoneurons (MNs) modifiable by locomotor training applied post
      transection. The purpose of this study was to investigate whether Sol and TA MNs
      adapt to changes in cholinergic environment by differential regulation of their
      muscarinic receptors M2 (M2R). We examined Chrm2 (M2R gene) transcript level,
      high-affinity 3-quinuclidinyl benzilate-3 H ([3 H]QNB) ligand binding,
      distribution and density of M2R immunolabeling in lumbar (L) segments in intact
      and SCT rats, with or without inclusion of 5-week treadmill locomotor training.
      We show that at the second week after SCT the levels of Chrm2 transcript are
      reduced in the L3-6 segments, with [3 H]QNB binding decreased selectively in the
      L5-6 segments, where ankle extensor MNs are predominantly located. At 5 weeks
      after SCT, [3 H]QNB binding differences between the L3-4 and L5-6 segments are
      maintained, accompanied by higher density of M2R immunolabeling in the plasma
      membrane and cytoplasm of TA than Sol MNs and by enriched synaptic versus
      extrasynaptic M2R pools (52% TA vs. 25% Sol MNs). Training normalized M2R in TA
      MNs, improved locomotion, and reduced frequency of clonic episodes. Our findings
      indicate higher sensitivity of TA than Sol MNs to cholinergic signaling after
      SCT, which might shorten flexor twitches duration and contribute to generation of
      clonic movements. Synaptic enrichment in M2R density may reflect a compensatory
      mechanism activated in TA and Sol MNs to different extent in response to reduced
      strength of cholinergic signaling to each MN pool. Open Practices Open Science:
      This manuscript was awarded with the Open Materials Badge. For more information
      see: https://cos.io/our-services/open-science-badges/.

PMID- 30102780
TI  - Genetics meets Therapy? Exome-wide association study reveals a loss-of-function
      variant in HSD17B13 (17-beta-hydroxysteroid dehydrogenase 13) that protects
      patients from liver damage and NAFLD-progression.
AB  - Knowledge of the genetic component of nonalcoholic fatty liver disease (NAFLD)
      has significantly contributed to the understanding of the disease pathogenesis.
      Genetic studies based either on genome wide association-strategies or candidate
      genes approaches showed that variants in loci involved in lipid metabolism and/or
      lipid-droplets biology have predominant and reproducible effects on the disease
      phenotype (1). However, it has been a major challenge to translate this
      information into molecularly-plausible and clinically-safe therapeutic targets.
      In fact, largest effects are given by missense variants (PNPLA3-I148M and TM6SF2
      E167K) that while explaining modest changes in gene / protein expression levels
      do not represent "druggable" targets. Specifically, variants associated with the
      progression of NAFLD or alcoholic liver disease (ALD) are located in genes with
      either pleiotropic metabolic effect/s, for instance PNPLA3-I148M (rs738409) (2),
      or are associated with dual and opposite effects on critical phenotypes,
      particularly TM6SF2-E167K variant (3). Consequently, any pharmaceutical drug
      targeted to modulate PNPLA3 or TM6SF2-enzymatic activity, would be of limited use
      because of potential undesirable effects. A new study by Abul-Husn et al. reveals
      that a loss-of-function variation in HSD17B13 (17-beta-hydroxysteroid
      dehydrogenase 13) gene confers protection against chronic liver injury and
      mitigates the progression of NAFLD and ALD in European Americans (4). These new
      findings open the possibility that therapeutic inhibition of HSD17B13 could
      represent a new strategy to treat NAFLD and ALD. This article is protected by
      copyright. All rights reserved.

PMID- 30102781
TI  - A systematic review of reviews of neurocognitive functioning in eating disorders:
      The state-of-the-literature and future directions.
AB  - OBJECTIVE: In recent years there has been increasing clinical and empirical
      interest in neurocognitive functioning in eating disorders (EDs), which has
      resulted in numerous quantitative and qualitative reviews. However, there has yet
      to be a comprehensive synthesis or critical review of this literature to identify
      future directions to advance the field in this area. Therefore the aim of this
      systematic review of systematic reviews was to (a) characterize the existing
      literature on neurocognitive functioning in EDs based on recent reviews (i.e.,
      published since 2010), (b) describe related limitations, and (c) suggest avenues
      for future research to address gaps in the current literature. METHOD: Electronic
      databases were queried for reviews of neurocognitive domains (i.e., inhibitory
      control, decision-making, central coherence, set-shifting, working memory, and
      attention bias) in EDs, which identified 28 systematic and meta-analytic reviews.
      RESULTS: Broadly, the literature indicates deficits across these neurocognitive
      domains in EDs, though heterogeneity was noted in the magnitude of these effects,
      which varied to some extent across ED subtypes, sample characteristics, and
      methodological approaches. DISCUSSION: While these reviews have generally
      suggested varying patterns of neurocognitive deficits across EDs, there remain
      critical limitations regarding the methodological quality of these studies (e.g.,
      the lack of prospective designs, consideration of confounding influences, or
      examination of interrelationships between neurocognitive domains and
      relationships between neurocognition and other relevant behavioral constructs).
      Specifically, we outline 10 key areas that are imperative to address in future
      research in this area in order to move our field forward.

PMID- 30102782
TI  - Innocent spectators, helping hands or a fifth column? Acute hepatitis A infection
      reveals important insights into bystander T cells.
AB  - Kim and colleagues studied a large cohort of adults with acute symptomatic HAV
      infection. They found pervasive and profound CD8 T cell activation in the blood
      of these patients, together with increased T cell proliferation and expression of
      cytotoxic molecules in a substantial proportion and often the majority of
      circulating CD8 T cells. The degree of overall activation, proliferation and
      cytotoxic capacity was tightly correlated with liver damage, as measured by ALT
      serum levels. Critically, they showed that this activated CD8 T cell phenotype
      was not limited to HAV-specific T cells but was found on multiple HAV-unrelated
      specificities they tested, i.e. CD8 T cells targeting influenza A virus (IAV),
      cytomegalovirus (CMV) and Epstein-Barr Virus (EBV). They then demonstrated that
      serum levels of IL-15 were elevated in acute HAV-infected patients and that IL-15
      is produced by HAV-infected cells in the liver and in in vitro cell culture.
      Together with the observation that IL-15 had the greatest potency to induce the
      same phenotypic and functional profiles of CD8 T cells in vitro this suggests a
      key role for this cytokine in the induction of this general CD8 T cell
      activation. The effect of IL-15 was shown to be independent of TCR stimulation,
      but rather mediated through the upregulation of NKG2D and NKp30 on HAV-unrelated
      virus-specific T cell populations, thus suggesting an innate-like rather than an
      antigen-specific cytotoxic T cell phenotype. The potential for these non-HAV
      specific CD8 T cells to inflict liver damage via an NKG2D based innate-like
      mechanism was further supported by the expression of the corresponding NKG2D
      receptors MIC-A and B on hepatocytes from HAV-infected livers. Indeed, the number
      of activated non-specific bystander CD8 T cells corresponded with the degree of
      liver damage, whereas the frequency of HAV-specific T cells seemed more
      correlated with viral control than with pathology. Overall, this study strongly
      supports a role for bystander CD8 T cell activity in acute HAV infection disease
      pathogenesis and identifies secretion of IL-15 by HAV-infected hepatocytes as the
      origin of an innate-like CD8 bystander response. This article is protected by
      copyright. All rights reserved.

PMID- 30102783
TI  - Fitting NTCP models to SBRT dose and carotid blowout syndrome data.
AB  - PURPOSE: To estimate the radiobiological parameters of three popular NTCP models,
      which describe the dose-response relations of carotid blowout syndrome (CBOS)
      after stereotactic body radiotherapy (SBRT). To evaluate the goodness-of-fit and
      the correlation of those models with CBOS. METHODS: The study included 61
      patients with inoperable locally recurrent head and neck cancer treated with SBRT
      using CyberKnife (Accuray, Sunnyvale, CA) at the Department of Radiation
      Oncology, Hacettepe University, Ankara, Turkey between June 2007 and March 2011.
      The dose-volume histograms of the internal carotid were exported from the plans
      of all the patients. The follow-up results regarding the end point of carotid
      blowout syndrome were collected retrospectively. Initially, univariable analyses
      (Wilcoxon rank-sum or Chi-square tests) and a multivariate logistic regression
      analysis were performed between the outcome data and a list of clinical and
      treatment factors to identify significant correlations. Additionally, the Lyman
      Kutcher-Burman (LKB), Relative Seriality (RS), and Logit NTCP models were used to
      fit the clinical data. The fitting of the different models was assessed through
      the area under the receiver operating characteristic curve (AUC), Akaike
      information criterion (AIC), and Odds Ratio methods. RESULTS: The
      clinical/treatment factors that were found to have a significant or close to
      significant correlations with acute CBOS were Age at the time of CK (P-value =
      0.03), Maximum carotid dose (P-value = 0.06), and CK prescription dose (P-value =
      0.08). Using Dmax , physical DVH, and EQD2 Gy -DVH as the dosimetric metrics in
      the NTCP models, the derived LKB model parameters were: (a) D50  = 45.8 Gy, m =
      0.24, n = n/a; (b) D50  = 44.8 Gy, m = 0.28, n = 0.01; and (c) D50  = 115.8 Gy, m
      = 0.45, n = 0.01, respectively. The AUC values for the dosimetric metrics were
      0.70, 0.68, and 0.61, respectively. The differences in AIC between the different
      models were less than 2 and ranged within +/-0.9. CONCLUSION: The maximum dose to
      the internal carotid less than 34 Gy appears to significantly reduce the risk for
      CBOS. Age at the time of CK, Maximum carotid dose, and CK prescription dose were
      also found to correlate with CBOS. The values of the parameters of three NTCP
      models were determined for this endpoint. A threshold of gEUD <34.5 Gy appears to
      be significantly associated with lower risks of CBOS.

PMID- 30102784
TI  - Resilience of Critical Infrastructures: Review and Analysis of Current
      Approaches.
AB  - In crisis situations, systems, organizations, and people must react and deal with
      events that are inherently unpredictable before they occur: vital societal
      functions and thus infrastructures must be restored or adapted as quickly as
      possible. This capacity refers to resilience. Progress concerning its
      conceptualization has been made but it remains difficult to assess and apply in
      practice. The results of this article stem from a literature review allowing the
      analysis of current advances in the development of proposals to improve the
      management of infrastructure resilience. The article: (i) identifies different
      dimensions of resilience; (ii) highlights current limits of assessing and
      controlling resilience; and (iii) proposes several directions for future research
      that could go beyond the current limits of resilience management, but subject to
      compliance with a number of constraints. These constraints are taking into
      account different hazards, cascade effects, and uncertain conditions, dealing
      with technical, organizational, economical, and human domains, and integrating
      temporal and spatial aspects.

PMID- 30102785
TI  - Effects of grasshoppers on prairies: Herbivore composition matters more than
      richness in three grassland ecosystems.
AB  - Understanding how biodiversity affects ecosystem processes is a key question in
      ecology. Previous research has found that increasing plant diversity often
      enhances many ecosystem processes, but less is known about the role of consumer
      diversity to ecosystem processes, especially in terrestrial ecosystems.
      Furthermore, we do not know how general biodiversity responses are among
      ecosystem types. We examined the role of insect herbivore (Orthoptera) diversity
      on plant production using parallel field experiments in three grassland
      ecosystems (mixed grass prairie, tallgrass prairie and coastal tallgrass prairie)
      to determine whether the effects of grasshopper diversity were consistent among
      sites. Using mesocosms, we manipulated orthopteran species richness (0, 1, 2, 3
      or 4 species), functional richness (number of functional feeding groups present;
      0, 1 or 2 functional groups) and functional composition (composition of
      functional groups present; mixed-feeders only, grass-feeders only, both mixed
      feeders and grass-feeders). Diversity treatments were maintained throughout the
      experiment by replacing dead individuals. Plant biomass was destructively sampled
      at the end of the experiment. We found no effect of species richness or
      functional richness on plant biomass. However, herbivore functional composition
      was important, and effects were qualitatively similar across sites: The presence
      of only grass-feeding species reduced plant biomass more than either mixed
      feeding species alone or both groups together. Orthopterans had consistent
      effects across a range of abiotic conditions, as well as different plant
      community and orthopteran community compositions. Our results suggest that
      functional composition of insect herbivores affects plant communities in
      grasslands more than herbivore species richness or functional richness, and this
      pattern was robust among grassland types.

PMID- 30102786
TI  - Vivax infection alters peripheral B-cell profile and induces persistent serum
      IgM.
AB  - B cell-mediated humoral responses are essential for controlling malarial
      infection. Studies have addressed the effects of Plasmodium falciparum infection
      on peripheral B-cell subsets but not much is known for P. vivax infection.
      Furthermore, majority of the studies investigate changes during acute infection,
      but not after parasite clearance. In this prospective study, we analysed
      peripheral B-cell profiles and antibody responses during acute P. vivax infection
      and upon recovery (30 days post-treatment) in a low-transmission area in India.
      Dengue patients were included as febrile-condition controls. Both dengue and
      malaria patients showed a transient increase in atypical memory B cells during
      acute infection. However, transient B cell-activating factor (BAFF)-independent
      increase in the percentage of total and activated immature B cells was observed
      in malaria patients. Naive B cells from malaria patients also showed increased
      TLR4 expression. Total IgM levels remained unchanged during acute infection but
      increased significantly at recovery. Serum antibody profiling showed a parasite
      specific IgM response that persisted at recovery. A persistent IgM autoantibody
      response was also observed in malaria but not dengue patients. Our data suggest
      that in hypoendemic regions acute P. vivax infection skews peripheral B-cell
      subsets and results in a persistent parasite-specific and autoreactive IgM
      response.

PMID- 30102787
TI  - A feasibility study of a 2-week self-compassionate letter-writing intervention
      for nontreatment seeking individuals with typical and atypical anorexia nervosa.
AB  - OBJECTIVE: Most individuals with anorexia nervosa (AN) do not seek treatment and
      shame is a common barrier. This study sought to determine whether a brief
      intervention designed to foster self-compassion would reduce shame and increase
      treatment motivation among nontreatment seeking individuals with AN. METHOD:
      Forty nontreatment seeking females with AN (75%) and atypical AN were randomly
      assigned to 2 weeks of a daily self-compassionate letter-writing intervention or
      a waitlist control condition. All participants completed pre, mid, and post
      questionnaires, and were weighed pre and post. RESULTS: The intervention yielded
      respectable credibility ratings and compliance and retained 95% of participants.
      Compared to the control condition, it produced greater increases in self
      compassion and greater decreases in shame and fears of self-compassion. BMI and
      readiness to get help for one's eating decreased in the control condition but did
      not change significantly in the intervention condition, though the motivation for
      treatment showed a trend toward increasing. Changes in eating pathology and
      readiness to get help for one's weight did not differ between conditions.
      DISCUSSION: Self-compassionate letter-writing may be an acceptable and feasible
      intervention for nontreatment seeking individuals with AN and might reduce
      certain barriers to help-seeking while improving psychological functioning.

PMID- 30102788
TI  - Re: A History of Pivotal Advances in Clinical Research Into Bone and Mineral
      Diseases.

PMID- 30102790
TI  - Response to: Another perspective on how visual neuroscience can inform the
      treatment of anorexia nervosa.

PMID- 30102789
TI  - Teriparatide Treatment Increases Mineral Content and Volume in Cortical and
      Trabecular Bone of Iliac Crest: A Comparison of Infrared Imaging With X-Ray-Based
      Bone Assessment Techniques.
AB  - Teriparatide increases bone mass primarily through remodeling of older or damaged
      bone and abundant replacement with new mineralizing bone. This post hoc analysis
      investigated whether dual-energy X-ray absorptiometric (DXA) areal bone mineral
      density (aBMD) measurement adequately reflects changes of mineral and organic
      matrix content in cortical and trabecular bone. Paired biopsies and aBMD
      measurements were obtained before and at end of 2 years of teriparatide treatment
      from postmenopausal women with osteoporosis who were either alendronate
      pretreated (mean, 57.5 months) or osteoporosis-treatment naive. Biopsies were
      assessed by micro-computed tomography (MUCT) to calculate mean cortical width
      (Ct.Wi), cortical area (Ct.Ar), and trabecular bone volume fraction (BV/TV).
      Fourier transformed infrared imaging (pixel size ~6.3 * 6.3 MUm2 ) was utilized
      to calculate mineral and organic matrix density (mean absorption/pixel), as well
      as total mineral and organic contents of cortical and cancellous compartments
      (sum of all pixels in the compartment). Effect of pretreatment over time was
      analyzed using mixed model repeated measures. MUCT derived Ct.Wi and BV/TV
      increased, accompanied by similar increases in the overall mineral contents of
      their respective bone compartments. Mineral density did not change. Marked
      increases in the total content of both mineral and organic matrix associated with
      volumetric growth in both compartments consistently exceeded those of aBMD.
      Increases in organic matrix exceeded increases in mineral content in both
      cortical and trabecular compartments. For percent changes, only change in Ct.Wi
      correlated to change in femoral neck aBMD (r = .38, p = 0.043), whereas no other
      significant correlations of Ct.Wi or BV/TV with lumbar spine, total hip, or
      femoral neck aBMD were demonstrable. These data indicate that 2 years of
      teriparatide treatment leads to an increased bone organic matrix and mineral
      content in the iliac crest. The magnitude of these increases in the iliac crest
      were not detected with conventional aBMD measurements at other skeletal sites.
      (c) 2018 American Society for Bone and Mineral Research.

PMID- 30102791
TI  - Multicenter feasibility study of bowel preparation with castor oil for colon
      capsule endoscopy.
AB  - BACKGROUND AND AIM: Extensive use of laxatives and incomplete excretion rates are
      problematic for colon capsule endoscopy (CCE). The aim of the present study was
      to determine the effectiveness of castor oil as a booster. METHODS: At four
      Japanese hospitals, 319 examinees undergoing CCE were enrolled retrospectively.
      Before and after the introduction of castor oil, other preparation reagents were
      unchanged. RESULTS: Of 319 examinees who underwent CCE, 152 and 167 examinees
      took regimens with castor oil (between November 2013 and June 2016) and without
      castor oil (between October 2015 and September 2017), respectively. Capsule
      excretion rates within its battery life in the groups with and without castor oil
      were 97% and 81%, respectively (P < 0.0001). Multivariate analysis showed that
      ages younger than 65 years (adjusted odds ratio [OR], 3.00; P = 0.0048), male
      gender (adjusted OR, 3.20; P = 0.0051), and use of castor oil (adjusted OR, 6.29;
      P = 0.0003) were predictors of capsule excretion within its battery life. Small
      bowel transit time was shorter and total volume of lavage and fluid intake was
      lower with castor oil than without (P = 0.0154 and 0.0013, respectively). Overall
      adequate cleansing level ratios with and without castor oil were 74% and 83%,
      respectively (P = 0.0713). Per-examinee sensitivity for polyps >=6 mm with and
      without castor oil was 83% and 85%, respectively, with specificities of 80% and
      78%, respectively. CONCLUSION: Bowel preparation with castor oil was effective
      for improving capsule excretion rate and reducing liquid loading.

PMID- 30102792
TI  - Intravenous immunoglobulins in Melkersson-Rosenthal syndrome: A clinical and
      neuroimaging study.

PMID- 30102793
TI  - Juvenile stress causes reduced locomotor behavior and dendritic spine density in
      the prefrontal cortex and basolateral amygdala in Sprague-Dawley rats.
AB  - Little has been investigated about the effects of stress on synaptic
      communication at prepubertal age, a stage considered as juvenile. This period of
      development is related to socialization through play. Our group has studied the
      changes of neuronal morphology in limbic structures caused by stress at prenatal
      and at early postnatal ages (before weaning) in the rat. In the present study, we
      assessed the effect of restraint stress at juvenile ages. Male Sprague-Dawley
      rats from postnatal day (PD) 21 to PD35 were restrained (from movement) for 2
      hrs. Locomotor activity in a novel environment was evaluated at three different
      ages, prepubertal PD38, pubertal PD50, and postpubertal PD68. Using the Golgi-Cox
      procedure, the dendritic morphology was evaluated in the pyramidal neurons of the
      prefrontal cortex (PFC), hippocampus, and basolateral amygdala (BLA). Juvenile
      stress caused a reduced locomotor activity at PD38 and PD68 together with
      reduction in dendritic spines after puberty in the PFC and at all the studied
      ages in the BLA. In addition, dendritic length was also reduced in the PFC at
      PD38 and PD68 and CA1 of the ventral hippocampus at PD50 and PD68. Our results
      suggest that stress in the juvenile stage can cause changes at the level of
      behavior and synaptic communication with an effect that remains until adulthood.

PMID- 30102795
TI  - Psoriasis dermatitis: an overlap condition of psoriasis and atopic dermatitis in
      children.

PMID- 30102794
TI  - Ca2+ and innate immune pathways are activated and differentially expressed in
      childhood asthma phenotypes.
AB  - BACKGROUND: Asthma is the most common chronic disease in children. Underlying
      immunologic mechanisms-in particular of different phenotypes-are still just
      partly understood. The objective of the study was the identification of distinct
      cellular pathways in allergic asthmatics (AA) and nonallergic asthmatics (NA) vs
      healthy controls (HC). METHODS: Peripheral blood mononuclear cells (PBMCs) of
      steroid-naive children (n(AA/NA/HC) = 35/13/34)) from the CLARA study (n = 275)
      were stimulated (anti-CD3/CD28, LpA) or kept unstimulated. Gene expression was
      investigated by transcriptomics and quantitative RT-PCR. Differentially regulated
      pathways between phenotypes were assessed after adjustment for sex and age (KEGG
      pathways). Networks based on correlations of gene expression were built using
      force-directed graph drawing. RESULTS: Allergic asthmatics vs NA and asthmatics
      overall vs HC showed significantly different expression of Ca2+ and innate
      immunity-associated pathways. PCR analysis confirmed significantly increased Ca2+
      -associated gene regulation (ORMDL3 and ATP2A3) in asthmatics vs HC, most
      prominent in AA. Innate immunity receptors (LY75, TLR7), relevant for virus
      infection, were also upregulated in AA and NA compared to HC. AA and NA could be
      differentiated by increased ATP2A3 and FPR2 in AA, decreased CLEC4E in AA, and
      increased IFIH1 expression in NA following anti-CD3/28 stimulation vs
      unstimulated (fold change). CONCLUSIONS: Ca2+ regulation and innate immunity
      response pattern to viruses were activated in PBMCs of asthmatics. Asthma
      phenotypes were differentially characterized by distinct regulation of ATP2A3 and
      expression of innate immune receptors (FPR2, CLEC4E, IFIH1). These genes may
      present promising targets for future in-depth investigation with the long-term
      goal of more phenotype-specific therapeutic interventions in asthmatics.

PMID- 30102796
TI  - Single injection of ketamine during mid-adolescence promotes long-lasting
      resilience to activity-based anorexia of female mice by increasing food intake
      and attenuating hyperactivity as well as anxiety-like behavior.
AB  - OBJECTIVE: This study tested the effects of ketamine on vulnerability of female
      adolescent mice to activity-based anorexia (ABA). METHOD: Twenty-four female
      C57Bl/6 J mice underwent ABA induction, which involved exposing wheel-acclimated
      adolescent mice to two bouts of food restriction (FR)-the first ABA (P41-44, mid
      adolescence) and the second ABA (P55-59, late adolescence), with recovery in
      between. Ketamine (3 or 30 mg/kg) or vehicle was given once, on the second day of
      FR of the first ABA (P42). Food consumption, body weight and wheel running
      activity were measured daily. Anxiety-like behaviors were accessed by elevated
      plus maze on P49 and P62, after weight restoration during the recovery phase.
      RESULTS: Ketamine (30 mg/kg) increased food intake during the first ABA (+38%, p
      = .015) and facilitated weight gain during recovery (+42%, p = .003). During the
      second ABA, the effect was manifested as increased food intake (+38%, p = .001)
      and weight gain (+47%, p = .001) while attenuating FR-induced wheel running
      activity (-24%, p = .09) and weight loss (-17%, p = .056). Ketamine also reduced
      anxiety-like behaviors. DISCUSSION: Thus, single injection of ketamine during mid
      adolescence effectively attenuates vulnerability of female mice to repeated ABA
      exposures.

PMID- 30102797
TI  - Right ventricular structure and function in senior and academy elite footballers.
AB  - AIMS: Right ventricular (RV) adaptation is a common finding in the athlete's
      heart. The aim of this study was to establish the extent of RV structural and
      functional adaptation in elite and academy professional footballers compared to
      age-matched controls. METHODS AND RESULTS: A total of 100 senior and 100 academy
      elite footballers and 20 senior and 19 academy age-matched controls were
      recruited. All participants underwent 2D, Doppler, tissue Doppler, and strain
      (epsilon) echocardiography of the right heart. Structural indices were derived
      and indexed allometrically for individual differences in body surface area.
      Standard RV function was assessed alongside peak RV epsilon and strain rate (SR).
      Senior football players had larger scaled RV structural parameters than academy
      players for the RV outflow (RVOTplax ) (32.7 +/- 4.2 and 29.5 +/- 4.0 mm(m2
      )0.326 , P < 0.001), the proximal RV outflow (RVOT1 ) (26.6 +/- 3.5 and 24.7 +/-
      3.9 mm(m2 )0.335 , P < 0.001), the basal RV inflow (RVD1 ) (33.1 +/- 4.1 and 30.7
      +/- 3.2 mm(m2 )0.404 , P = 0.020), RV length (RVD3 ) (66.5 +/- 6.1 and 62.9 +/-
      5.1 mm(m2 )0.431 , P < 0.001), and RV diastolic area (RVDarea ) (16.9 +/- 2.6 and
      15.7 +/- 2.6 mm(m2 )0.735 , P < 0.001). Both academy and senior football players
      demonstrated larger scaled structural RV parameters in comparison with age
      matched controls. Systolic SR (SRS) was lower in the senior players compared to
      academy players in the mid (-1.52 +/- 0.49 and -1.41 +/- 0.34 L/s, P = 0.019) and
      apical (-1.97 +/- 0.74 and -1.72 +/- 0.42 L/s, P = 0.025) wall regions,
      respectively. CONCLUSION: Right ventricular structural adaptation occurs in both
      senior and academy football players with senior players having larger RV
      dimensions. Although senior players have slightly lower peak SRS than academy
      players, all global epsilon and SR are within normal ranges.

PMID- 30102798
TI  - Blockade of vascular endothelial growth factor receptor 2 inhibits intraplaque
      haemorrhage by normalization of plaque neovessels.
AB  - BACKGROUND: Plaque angiogenesis is associated with atherosclerotic lesion growth,
      plaque instability and negative clinical outcome. Plaque angiogenesis is a
      natural occurring process to fulfil the increasing demand of oxygen and
      nourishment of the vessel wall. However, inadequate formed, immature plaque
      neovessels are leaky and cause intraplaque haemorrhage. OBJECTIVE: Blockade of
      VEGFR2 normalizes the unbridled process of plaque neovessel formation and induces
      maturation of nascent vessels resulting in prevention of intraplaque haemorrhage
      and influx of inflammatory cells into the plaque and subsequently increases
      plaque stability. METHODS AND RESULTS: In human carotid and vein graft
      atherosclerotic lesions, leaky plaque neovessels and intraplaque haemorrhage co
      localize with VEGF/VEGFR2 and angiopoietins. Using hypercholesterolaemic
      ApoE3*Leiden mice that received a donor caval vein interposition in the carotid
      artery, we demonstrate that atherosclerotic vein graft lesions at t28 are
      associated with hypoxia, Hif1alpha and Sdf1 up-regulation. Local VEGF
      administration results in increased plaque angiogenesis. VEGFR2 blockade in this
      model results in a significant 44% decrease in intraplaque haemorrhage and 80%
      less extravasated erythrocytes compared to controls. VEGFR2 blockade in vivo
      results in a 32% of reduction in vein graft size and more stable lesions with
      significantly reduced macrophage content (30%), and increased collagen (54%) and
      smooth muscle cell content (123%). Significant decreased VEGF, angiopoietin-2 and
      increased Connexin 40 expression levels demonstrate increased plaque neovessel
      maturation in the vein grafts. VEGFR2 blockade in an aortic ring assay showed
      increased pericyte coverage of the capillary sprouts. CONCLUSION: Inhibition of
      intraplaque haemorrhage by controlling neovessels maturation holds promise to
      improve plaque stability.

PMID- 30102799
TI  - Expression of T-cell receptor signalling pathway components in extranodal NK/T
      cell lymphoma.
AB  - AIMS: Although the neoplastic cells of extranodal natural killer (NK)/T-cell
      lymphoma (ENKTL) usually do not express T-cell antigens, the T-cell receptor
      (TCR) gene might be rearranged and TCR protein expressed. The aim is to elucidate
      the expression of the downstream TCR pathway components and their importance in
      ENKTL. METHODS AND RESULTS: We used formalin-fixed paraffin-embedded tissues from
      91 ENKTL samples to immunohistochemically characterise the expression of TCR
      pathway components. The following proteins were variably expressed: ZAP70 (94%;
      83/88), GRAP2/GADS (68%; 60/88), DOK2 (42%; 38/90), LCK (35%; 31/88), and ITK
      (10%; 9/90). When these tumours were classified as being of T lineage (16%), NK
      lineage (45%), or indeterminate lineage (38%), the GRAP2/GADS expression rate was
      higher in T lineage tumours (versus NK, P = 0.0073; versus indeterminate, P =
      0.00082). GRAP2/GADS-positive NK lineage tumours more frequently expressed DOK2
      (P = 0.0073), and were more often confined to the nasal areas (P = 0.014).
      Furthermore, when these tumours were immunophenotypically classified into a T
      signature (42%) or NK signature (58%), the expression rates of GRAP2/GADS and ITK
      were higher in T signature tumours (P = 0.00074 and P = 0.067, respectively),
      whereas that of LCK was higher in NK-signature tumours (P = 0.10). CONCLUSIONS:
      Although some ENTKL cases were polyclonal for TCR rearrangement and others lacked
      TCR expression, we speculate that the TCR pathway might be functioning in ENKTLs.
      A T signature versus a NK signature might be better for delineating the
      physiology of ENKTL than cellular lineage. Furthermore, ITK may represent a
      potential therapeutic target for patients with ITK-expressing tumours.

PMID- 30102800
TI  - An experiment on the impact of coaches' and athlete leaders' competence support
      on athletes' motivation and performance.
AB  - PURPOSE: Grounded in the Cognitive Evaluation Theory, the present experiment
      aimed to compare the relative impact of competence support provided by coaches
      versus athlete leaders on players' competence satisfaction, intrinsic motivation,
      and performance. METHODS: We recruited 18 existing competitive male basketball
      teams (ie, 126 players) to participate in the experiment. Each team was randomly
      assigned to one of three conditions: (a) the coach provided competence support
      (ie, by encouraging, providing positive feedback, and expressing team
      confidence); (b) the athlete leader provided competence support; or (c) neither
      the coach, nor the athlete leader provided competence support (ie, control
      condition). RESULTS: Teams in which the athlete leader provided competence
      support reported higher levels of competence satisfaction and intrinsic
      motivation than teams in the control condition, a difference that did not emerge
      when the coach provided competence support. Furthermore, teams in which either
      the coach or the athlete leader supported team members' competence performed
      better compared to teams in the control group. CONCLUSION: Our findings highlight
      the importance of providing competence support to enhance team performance. Given
      athlete leaders' unique impact on teammates' competence satisfaction and
      motivation, instructing athlete leaders how to provide competence support
      constitutes an important motivational pathway for coaches to optimize team
      functioning.

PMID- 30102801
TI  - Reduced vitamin D levels in painful diabetic peripheral neuropathy.
AB  - AIM: Recent studies have reported an association between low vitamin D levels and
      diabetic peripheral neuropathy. However, many of these did not differentiate
      between people with painful diabetic peripheral neuropathy and those with
      painless diabetic peripheral neuropathy, or assess major confounding factors
      including sunlight exposure and daily activity. Our study addressed these
      limitations and evaluated vitamin D levels in people with carefully phenotyped
      diabetic peripheral neuropathy and controls. METHODS: Forty-five white Europeans
      with Type 2 diabetes and 14 healthy volunteers underwent clinical and
      neurophysiological assessments. People with Type 2 diabetes were then divided
      into three groups (17 with painful diabetic peripheral neuropathy, 14 with
      painless diabetic peripheral neuropathy and 14 with no diabetic peripheral
      neuropathy). All had seasonal sunlight exposure and daily activity measured,
      underwent a lower limb skin biopsy and had 25-hydroxyvitamin D measured during
      the summer months, July to September. RESULTS: After adjusting for age, BMI,
      activity score and sunlight exposure, 25-hydroxyvitamin D levels (nmol/l) (se)
      were significantly lower in people with painful diabetic peripheral neuropathy
      [painful diabetic peripheral neuropathy 34.9 (5.8), healthy volunteers 62.05
      (6.7), no diabetic peripheral neuropathy 49.6 (6.1), painless diabetic peripheral
      neuropathy 53.1 (6.2); ANCOVAP = 0.03]. Direct logistic regression was used to
      assess the impact of seven independent variables on painful diabetic peripheral
      neuropathy. Vitamin D was the only independent variable to make a statistically
      significant contribution to the model with an inverted odds ratio of 1.11. Lower
      25-hydroxyvitamin D levels also correlated with lower cold detection thresholds
      (r = 0.39, P = 0.02) and subepidermal nerve fibre densities (r = 0.42, P = 0.01).
      CONCLUSIONS: We have demonstrated a significant difference in 25-hydroxyvitamin D
      levels in well-characterized people with painful diabetic peripheral neuropathy,
      while accounting for the main confounding factors. This suggests a possible role
      for vitamin D in the pathogenesis of painful diabetic peripheral neuropathy.
      Further prospective and intervention trials are required to prove causality
      between low vitamin D levels and painful diabetic peripheral neuropathy.

PMID- 30102802
TI  - Changing profile of eating disorders between 1963 and 2004 in a Japanese sample.
AB  - OBJECTIVE: The purpose of this study was to investigate possible changes in the
      demographic and clinical characteristics of Japanese patients with eating
      disorders using a consecutive series of patients who presented at Kyoto
      University Hospital between 1963 and 2004. We also studied cultural factors
      related to eating disorders over time. METHOD: We completed a retrospective
      review of a cohort of patients using a checklist based on the DSM-5 diagnostic
      criteria. Patients seen from 1963 to 1974 (Period I, n = 26), 1975 to 1984
      (Period II, n = 97), 1985 to 1994 (Period III, n = 540), and 1995 to 2004 (Period
      IV, n = 700) were compared. RESULTS: In this study, patients with restrictive
      eating appeared in the early 1960s. Patients with binge eating and purging
      behaviors appeared in the mid-1970s and thereafter increased over time. The
      number of patients with anorexia nervosa and bulimia nervosa dramatically
      increased in Period III. The proportion of patients with binge eating increased,
      while the proportion of patients with restrictive eating decreased over time. All
      patients with anorexia nervosa in the 1960s had fat phobia and disturbed body
      image, but none of them reported dieting for slimness. DISCUSSION: The prevalence
      and clinical characteristics of patients with eating disorders significantly
      changed across the four time periods. In terms of cultural factors, present
      findings suggest that factors beyond industrialization, modernization and
      westernization may be necessary for the development of eating disorders, and
      these factors may change with the times.

PMID- 30102803
TI  - Localization of double-bond positions in lipids by tandem mass spectrometry
      succeeding high-performance liquid chromatography with post-column
      derivatization.

PMID- 30102804
TI  - Adverse pathologic features in T1/2 oral squamous cell carcinoma classified by
      the American Joint Committee on Cancer eighth edition and implications for
      treatment.
AB  - BACKGROUND: The American Joint Committee on Cancer (AJCC) eighth edition has
      incorporated depth of invasion into TNM classification of oral cavity squamous
      cell carcinoma (SCC) due to the prognostic impact on recurrence and survival.
      After reclassifying our patients with T1 to T2 oral cavity SCC according to these
      recommendations, we intended to study the effect of adverse pathological features
      (perineural invasion [PNI], lymphovascular invasion, and differentiation) on
      overall survival (OS). METHODS: We conducted a retrospective analysis of 442
      patients with T1 to T2 oral cavity SCC. Univariate and multivariate analysis was
      performed for impact of adverse pathological features on OS. RESULTS: For the
      newly reclassified T1 to T2 oral cavity tumors, on multivariate analysis, the
      prognostically relevant parameters were PNI (P = .032) and differentiation (P =
      .009). Increasing adverse pathological features resulted in worse survival (P =
      .005). CONCLUSION: Incorporation of PNI and differentiation better reflect
      prognostic outcome in oral cavity tumors classified as T1 to T2 as per the new
      AJCC eighth edition. Increasing adverse pathological features resulted in worse
      survival.

PMID- 30102805
TI  - Surface Modification on Pd-TiO2 Hybrid Nanostructures towards Highly Efficient H2
      Production from Catalytic Formic Acid Decomposition.
AB  - Metal-containing nanocrystals with well-designed surface structures represent a
      class of model systems for revealing the fundamental physical and chemical
      processes involved in heterogeneous catalysis. Herein it is shown how surface
      modification can be utilized as an efficient strategy for controlling the surface
      electronic state of catalysts and, thus, for tuning their catalytic activity. As
      model catalysts, the Pd-tetrahedron-TiO2 nanostructures, modified on the surface
      with different foreign atoms, showed a varied activity in the catalytic
      decomposition of formic acid towards H2 production. The catalytic activity
      increases with a reduction in the work function of modified atoms; this reduction
      can be well explained by a surface polarization mechanism. In this hybrid system,
      the difference in the work functions of Pd and modified atoms results in surface
      polarization on the Pd surface and, thus, in the tuning of its charge state.
      Together with the Schottky junction between TiO2 and metals, the tuned charge
      state enables the promotion of catalytic efficiency in the catalytic
      decomposition of formic acid to H2 and CO2 .

PMID- 30102806
TI  - Antiproliferative potential of miR-33a in laryngeal cancer Hep-2 cells via
      targeting PIM1.
AB  - BACKGROUND: Laryngeal cancer is a frequent cause of cancer-associated mortality
      worldwide with an overall poor prognosis along with high mortality rates.
      Therefore, comprehensive investigation of underlying molecular mechanisms of
      laryngeal carcinogenesis remains an important problem. METHODS: In this study,
      proliferative and apoptotic features of Hep-2 cells overexpressing microRNA-33a
      (miR-33a) were evaluated and in silico analysis along with literature search was
      used to find putative targets of miR-33a. The potential of PIM1 (pim-1 oncogene)
      as a direct target of miR-33a was tested using quantitative real-time polymerase
      chain reaction, Western blot, and luciferase assay. RESULTS: Induced miR-33a
      expression significantly inhibited proliferation through inducing apoptosis of
      Hep-2 cells. Further in vitro tests showed downregulation of PIM1 in messenger
      ribonucleic acid (mRNA) and protein level upon miR-33a overexpression and
      confirmed PIM1 as a direct target of miR-33a. CONCLUSIONS: Mir-33a was
      demonstrated to act as a tumor suppressor in larnygeal cancer via directly
      targeting the 3' untranslated region of PIM1.

PMID- 30102807
TI  - PUVA and interferon alpha2b combined therapy for patients with mycosis fungoides
      at different stages of the disease: a seven-year retrospective study in Russia.

PMID- 30102808
TI  - eDoctor: machine learning and the future of medicine.
AB  - Machine learning (ML) is a burgeoning field of medicine with huge resources being
      applied to fuse computer science and statistics to medical problems. Proponents
      of ML extol its ability to deal with large, complex and disparate data, often
      found within medicine and feel that ML is the future for biomedical research,
      personalized medicine, computer-aided diagnosis to significantly advance global
      health care. However, the concepts of ML are unfamiliar to many medical
      professionals and there is untapped potential in the use of ML as a research
      tool. In this article, we provide an overview of the theory behind ML, explore
      the common ML algorithms used in medicine including their pitfalls and discuss
      the potential future of ML in medicine.

PMID- 30102809
TI  - Revision surgery for failed anterior cruciate ligament reconstruction with
      extension deficiency.
AB  - BACKGROUND: Some patients with recurrent symptomatic instability after primary
      anterior cruciate ligament (ACL) reconstruction have an extension deficiency
      (ED). This study (a) compared preoperative clinical conditions between the ED and
      non-ED groups undergoing revision ACL reconstruction, (b) documented clinical and
      arthroscopic findings in ACL-reconstructed patients with reinstability and ED,
      and (c) determined whether the ED could be resolved and whether the clinical
      results of revision surgery differed between the ED and non-ED groups. METHODS:
      This study included 58 patients who underwent revision ACL reconstruction.
      Patients were divided into the ED and non-ED groups. Preoperatively, the
      demographics and clinical conditions of the two groups were compared.
      Intraoperatively, the pathological structures that related to ED were documented.
      After surgery, the degree of postoperative ED and functional outcomes were
      compared between the two groups at 2-year follow-up. RESULTS: The International
      Knee Documentation Committee subjective score and SF-36 physical component
      summary scores were worse in the ED group than the non-ED group preoperatively
      (54 vs 48 [P = 0.014]; 42 vs 39 [P = 0.031], respectively). Intraoperatively, the
      ED group showed significantly more frequent graft malposition (50% vs 5%), anvil
      osteophytes (44% vs 0%), and scarring around posterior intercondylar notch (100%
      vs 0%). However, there was no difference in the degree of postoperative ED and
      functional outcome between the two groups at follow-up. CONCLUSIONS: ED in
      patients with recurrent instability after primary ACL reconstruction could be
      treated with good clinical result by addressing the pathological conditions
      causing ED in addition to ACL re-reconstruction.

PMID- 30102810
TI  - Grab my tail: evolution of dazzle stripes and colourful tails in lizards.
AB  - Understanding the functions of animal coloration has been a long-standing
      question in evolutionary biology. For example, the widespread occurrence of
      striking longitudinal stripes and colourful tails in lizards begs for an
      explanation. Experiments have suggested that colourful tails can deflect attacks
      towards the tail (the 'deflection' hypothesis), which is sacrificable in most
      lizards, thereby increasing the chance of escape. Studies also suggest that in
      moving lizards, longitudinal body stripes can redirect predators' strikes towards
      the tail through the 'motion dazzle' effect. Despite these experimental studies,
      the ecological factors associated with the evolution of such striking colorations
      remain unexplored. Here, we investigated whether predictions from motion dazzle
      and attack deflection could explain the widespread occurrence of these striking
      marks using comparative methods and information on eco-physiological variables
      (caudal autotomy, diel activity, microhabitat and body temperature) potentially
      linked to their functioning. We found both longitudinal stripes and colourful
      tails are associated with diurnal activity and with the ability to lose the tail.
      Compared to stripeless species, striped species are more likely to be ground
      dwelling and have higher body temperature, emphasizing the connection of stripes
      to mobility and rapid escape strategy. Colourful tails and stripes have evolved
      multiple times in a correlated fashion, suggesting that their functions may be
      linked. Overall, our results together with previous experimental studies support
      the notion that stripes and colourful tails in lizards may have protective
      functions based on deflective and motion dazzle effects.

PMID- 30102811
TI  - Analgesic and anti-inflammatory drugs in sports: Implications for exercise
      performance and training adaptations.
AB  - Over-the-counter analgesics, such as anti-inflammatory drugs (NSAIDs) and
      paracetamol, are widely consumed by athletes worldwide to increase pain
      tolerance, or dampen pain and reduce inflammation from injuries. Given that these
      drugs also can modulate tissue protein turnover, it is important to scrutinize
      the implications of acute and chronic use of these drugs in relation to exercise
      performance and the development of long-term training adaptations. In this
      review, we aim to provide an overview of the studies investigating the effects of
      analgesic drugs on exercise performance and training adaptations relevant for
      athletic development. There is emerging evidence that paracetamol might acutely
      improve important endurance parameters as well as aspects of neuromuscular
      performance, possibly through increased pain tolerance. Both NSAIDs and
      paracetamol have been demonstrated to inhibit cyclooxygenase (COX) activity,
      which might explain the reduced anabolic response to acute exercise bouts.
      Consistent with this, NSAIDs have been reported to interfere with muscle
      hypertrophy and strength gains in response to chronic resistance training in
      young individuals. Although it remains to be established whether any of these
      observations also translate into detriments in sport-specific performance or
      reduced training adaptations in elite athletes, the extensive use of these drugs
      certainly raises practical, ethical, and important safety concerns that need to
      be addressed. Overall, we encourage greater awareness among athletes, coaches,
      and support staff on the potential adverse effects of these drugs. A risk-benefit
      analysis and professional guidance are strongly advised before the athlete
      considers analgesic medicine for training or competition.

PMID- 30102812
TI  - Impact of different glycaemic treatment targets on pregnancy outcomes in
      gestational diabetes.
AB  - AIM: With no current randomized trials, we explored the impact of tight compared
      with standard treatment targets on pregnancy outcomes in gestational diabetes
      mellitus (GDM). METHODS: This cohort study of singleton births >= 28 weeks'
      gestation was conducted at two major Australian maternity services (2009-2013).
      Standardized maternal, neonatal and birth outcomes were examined using routine
      healthcare data and compared for women with GDM at Service One (n = 2885) and
      Service Two (n = 1887). Services applied different treatment targets: Service One
      (standard targets, reference group) fasting < 5.5 mmol/l, 2-h postprandial < 7.0
      mmol/l; Service Two (tight targets) fasting < 5.0 mmol/l, 2-h postprandial < 6.7
      mmol/l. Multivariable regression with propensity score adjustment was used to
      examine associations between targets and outcomes. RESULTS: GDM prevalence and
      insulin use were 7.9% and 31% at Service One, and 5.7% and 46% at Service Two.
      There were no differences in primary outcomes: birthweight > 90th centile
      [adjusted odds ratio (OR) 1.06, 95% confidence interval (CI) 0.87-1.30] and <
      10th centile (OR 0.84, 95% CI 0.70-1.01), or secondary outcomes gestational
      hypertension, pre-eclampsia, shoulder dystocia or a perinatal composite. Service
      Two with tight targets had increased induction of labour (OR 3.63, 95% CI 3.17
      4.16), elective Caesarean section (OR 1.75, 95% CI 1.37-2.23) and Apgar scores <
      7 at 5 min (OR 1.54, 95% CI 1.05-2.25), decreased hypoglycaemia (OR 0.76, 95% CI
      0.61-0.94]), jaundice (OR 0.47, 95% CI 0.35-0.63) and respiratory distress (OR
      0.68, 95% CI 0.47-0.98). CONCLUSIONS: Tight GDM treatment targets were associated
      with greater insulin use and no difference in primary birthweight outcomes. The
      service with tight targets had higher obstetric intervention, lower rates of
      reported hypoglycaemia, jaundice, respiratory distress and lower Apgar scores.
      High-quality interventional data are required before tight treatment targets can
      be implemented.

PMID- 30102813
TI  - Analysis of readmissions after transoral robotic surgery for oropharyngeal
      squamous cell carcinoma.
AB  - BACKGROUND: As transoral robotic surgery (TORS) is being increasingly used to
      treat patients with oropharyngeal squamous cell carcinoma (OPSCC), there is an
      interest in determining contributors to readmission. METHODS: We conducted this
      retrospective multivariate analysis modeling 30-day readmission using the
      Nationwide Readmissions Database (2012-2014). RESULTS: Of 950 patients, 117
      (12.3%) were readmitted. Hemorrhage and diet/aspiration accounted for 32.5% and
      19.7% of readmissions, respectively. Of those readmitted, 23.1% required
      operative bleeding control, 11.1% required transfusion, 1.7% required
      tracheostomy, and 18.8% required gastrostomies. Those readmitted were older (mean
      63.2 years, SD 9.5 vs 60.9 mean years, SD 10.3) and had longer hospitalizations
      (mean 5.7 days, SD 6.8 vs mean 4.3 days, SD 4.1) and higher rates of
      aspiration/pneumonia (9.4% vs 2.4%, P < .01) on index admission. Multivariate
      analysis demonstrated that aspiration/pneumonia on index admission was
      independently associated with readmission (OR 3.128, 95% CI 1.178-8.302).
      CONCLUSIONS: Of the patients 12.3% were readmitted within 30 days with hemorrhage
      and diet complications as significant contributors.

PMID- 30102814
TI  - The Myo-inositol pathway does not contribute to ascorbic acid synthesis.
AB  - Ascorbic acid (AsA) biosynthesis in plants predominantly occurs via a pathway
      with d-mannose and l-galactose as intermediates. One alternative pathway for AsA
      synthesis, which is similar to the biosynthesis route in mammals, is
      controversially discussed for plants. Here, myo-inositol is cleaved to glucuronic
      acid and then converted via l-gulonate to AsA. In contrast to animals, plants
      have an effective recycling pathway for glucuronic acid, being a competitor for
      the metabolic rate. Recycling involves a phosphorylation at C1 by the enzyme
      glucuronokinase. Two previously described T-DNA insertion lines in the gene
      coding for glucuronokinase1 show wild type-like expression levels of the mRNA in
      our experiments and do not accumulate glucuronic acid in labelling experiments
      disproving that these lines are true knockouts. As suitable T-DNA insertion lines
      were not available, we generated frameshift mutations in the major expressed
      isoform glucuronokinase1 (At3g01640) to potentially redirect metabolites to AsA.
      However, radiotracer experiments with 3 H-myo-inositol revealed that the mutants
      in glucuronokinase1 accumulate only glucuronic acid and incorporate less
      metabolite into cell wall polymers. AsA was not labelled, suggesting that
      Arabidopsis cannot efficiently use glucuronic acid for AsA biosynthesis. All four
      mutants in glucuronokinase as well as the wild type have the same level of AsA in
      leaves.

PMID- 30102815
TI  - No evidence of disease activity in people with multiple sclerosis.

PMID- 30102816
TI  - Hemodialysis-related headache and how to prevent it.
AB  - BACKGROUND AND PURPOSE: Hemodialysis (HD) may have some adverse effects on the
      nervous system. Headache is the most commonly reported neurological symptom
      amongst HD patients. Our aim was to determine the frequency, clinical
      characteristics and triggering factors of HD-related headache (HRH) and to
      evaluate preventive strategies for reducing HRH. METHOD: In all, 494 patients
      were included. Comparative controls (CC) were classified within the same patients
      without headache. Arterial systolic/diastolic blood pressure, blood urea nitrogen
      (BUN) and creatinine were correlated before/after one HD. The urea reduction
      ratio during the dialysis session was determined. RESULTS: A total of 175
      patients (35.4%) with a mean age of 57.3 +/- 15.7 years were diagnosed with HRH.
      HRH was more common in males (P < 0.001). Headache was started a mean of 2.90 +/-
      0.86 h after the HD. The common localization of pain was reported to be bifrontal
      in 41.7% (n = 73). The mean duration of headache was 6.22 +/- 7.8 h, with a
      duration of <=4 h reported by 64.0% of patients. The mean Visual Analog Scale
      score was 5.64 +/- 2.05. The differences between pre/post-dialysis BUN values
      were 94.6 +/- 31.1 in HRH patients and 86.8 +/- 28.5 in the CC group (P = 0.006).
      The systolic blood pressure difference between the pre/post-dialysis measurements
      was 22.4 +/- 16.5 mmHg in HRH patients and 12.8 +/- 19.4 mmHg in CC(P < 0.001).
      Patients with HRH had significantly higher mean systolic and diastolic blood
      pressure pre-dialysis values (systolic, P = 0.002; diastolic, P < 0.001). The
      differences in systolic/diastolic blood pressure between pre/post-dialysis were
      higher in the HRH group (P < 0.001, P = 0.001, respectively). CONCLUSION:
      Regulating the frequency and timing of dialysis may provide better management in
      HRH with high BUN levels and high pre-dialysis blood pressure.

PMID- 30102817
TI  - Trends and Characterization of Academic Emergency Department Patient Visits: A
      Five-year Review.
AB  - OBJECTIVES: To meet the unique comparative data needs of academic emergency
      departments (EDs), we describe the recent 5-year national and regional trends for
      adult emergency patients' characteristics and operational parameters at academic
      emergency medical centers. METHODS: Data collected from the recent 5-year period
      academic year (AY) 2012 through AY 2016 of the Academy of Administrators in
      Academic Emergency Medicine (AAAEM) and the Association of Academic Chairs of
      Emergency Medicine (AACEM) Academic Emergency Medicine Benchmarking Survey were
      analyzed for trends in 1) ED volumes and modes of arrival, 2) triage acuity
      level, 3) trends in ED professional fee billing, and 4) disposition patterns of
      ED patients including admission rates and walkouts. The AY spanned the 12-month
      period of July 1 through June 30. Only primary academic or academic affiliate
      hospitals data were included. Community and freestanding affiliated EDs were
      excluded. Institutional-specific data were stratified into four cohorts based on
      the following annual ED visit volumes: under 40,000, 40,000 to 60,000, 60,000 to
      80,000, and over 80,000. Triage acuity levels were based on the Emergency
      Severity Index (ESI). Professional fee billing was analyzed specifically for CPT
      codes 99284, 99285, and 99291 (critical care). Left without being seen (LWBS),
      defined as leaving before a screening examine by a licensed medical provider, and
      screened and left (SAL), i.e., patients who were screened by a provider, but left
      before definitive evaluation and management, were similarly evaluated. Total
      walkouts were defined as the sum of LWBS and SAL. RESULTS: Forty-four primary
      academic and academic affiliate sites completed the survey for all 5 years. The
      mean annual patient census increased 13.4% over the study period, with the
      majority (80%) of sites experiencing volume growth. Acuity/illness severity,
      measured as ESI 1 and 2, and CPT codes 99284, 99295, and 99291 increased an
      aggregate 18.2 and 8.4%, respectively. Large-volume hospitals (>60,000-80,000,
      >80,000) admissions increased by 15 and 21.6%, respectively, primarily due to
      surge in 2016. Overall emergency medical services (EMS) arrivals increased 7.3%
      although admissions from EMS remained relatively stable. LWBS rates decreased
      19.5%, but total walkouts did not appear to change. CONCLUSION: With a focus on
      larger academic institutions, differences were noted in the overall increases in
      volume and acuity. In this survey, participating institutions experienced
      increased volumes of patients with seemingly higher illness severity. While
      inroads have been made in LWBS rates, there has not been an overall decrease in
      total walkouts. The data reported here differed in many aspects compared to other
      benchmark surveys.

PMID- 30102818
TI  - Assessment of autonomic innervation of the foot in familial amyloid
      polyneuropathy.
AB  - BACKGROUND AND PURPOSE: Distal involvement of autonomic nerve fibers is critical
      in familial amyloid polyneuropathy (FAP) due to transthyretin (TTR) mutation.
      This study compares different methods for assessing autonomic foot innervation in
      TTR-FAP patients. METHODS: Three groups of seven TTR-FAP patients were included,
      according to disease severity: clinically asymptomatic, moderate or advanced
      neuropathy. The autonomic investigation included the eutectic mixture of local
      anesthetics test and laser Doppler flowmetry for vasomotor aspects and the
      Sudoscan(r) (measuring electrochemical skin conductance) and Neuropad(r) test for
      sudomotor aspects. Somatic innervation was assessed by performing nerve
      conduction studies, quantitative sensory testing [including vibration, cold and
      warm detection threshold (WDT) measurements] and laser evoked potentials.
      RESULTS: The results of all neurophysiological tests varied according to TTR-FAP
      severity (P <= 0.01, Kruskal-Wallis test), except for the eutectic mixture of
      local anesthetics test and laser Doppler flowmetry variables. In addition, the
      sudomotor tests (Sudoscan or Neuropad) or WDT measurement provided early markers
      of neuropathy in two of the seven asymptomatic carriers. Finally, all
      neurophysiological results correlated with the Neuropathy Impairment Score (r
      values between -0.88 and -0.66, P < 0.005, Spearman test), except the cold
      detection threshold. CONCLUSIONS: The Neuropad test could be used to detect TTR
      FAP onset, but confirmation requires electrochemical skin conductance and WDT
      measurement. The Sudoscan technique, but not the Neuropad test (at least assessed
      at a fixed time point), could be valuable to follow the progression of the
      neuropathy. Follow-up investigation should also include large-fiber investigation
      (e.g. nerve conduction studies and vibration detection threshold). Conversely,
      reliable tests for assessing vasomotor disturbances in limb extremities of TTR
      FAP patients are still awaited.

PMID- 30102819
TI  - Fetal microchimerism by mode of delivery: a prospective cohort study.
AB  - OBJECTIVE: To compare fetal microchimerism (FMc) in pregnancies with
      uncomplicated vaginal delivery (VD) versus caesarean delivery (CD). DESIGN:
      Prospective cohort study. SETTING: University of Washington and Fred Hutchinson
      Cancer Research Center, USA. POPULATION: Women delivering singleton pregnancies
      without pertinent antenatal complications with uncomplicated deliveries (n = 36).
      METHODS: We collected maternal predelivery, postdelivery and umbilical cord blood
      for each mother-baby pair. Following maternal and fetal genotyping, FMc was
      measured with quantitative polymerase chain reaction assays targeting fetus
      specific polymorphisms. Quantification of FMc is expressed as genome equivalents
      (gEq) of fetal DNA/100 000 total gEq tested. FMc detection was evaluated by
      logistic regression while controlling for total number of cell equivalents tested
      and clinically relevant covariates. FMc concentrations were compared using
      negative binomial regression while controlling for the same covariates and
      predelivery FMc positivity. MAIN OUTCOME MEASURE: Detection and concentration of
      FMc by mode of delivery. RESULTS: Twenty-four mother-baby pairs had a VD and 12
      had a CD. Postdelivery FMc detection was higher following CD than after VD (58.3%
      versus 16.7%, P = 0.02). After controlling for covariates, the likelihood of
      postdelivery FMc detection was almost nine-fold higher after CD than VD (odds
      ratio 8.8, 95% CI 1.6-47.6; P = 0.01). With respect to postdelivery FMc
      concentration, the detection rate ratio for CD versus VD in the adjusted negative
      binomial regression model was 14.7 (95% CI 3.2-66.8; P = 0.001). CONCLUSION:
      Postdelivery peripheral FMc detection and concentration are significantly higher
      after CD than after VD. As FMc is associated with long-term maternal health, our
      findings suggest that the mode of delivery may impact this risk. TWEETABLE
      ABSTRACT: Greater fetal microchimerism found in maternal blood following
      caesarean delivery compared with vaginal delivery.

PMID- 30102820
TI  - Kidney transplant recipients with polycystic kidney disease have a lower risk of
      post-transplant BK infection than those with end-stage renal disease due to other
      causes.
AB  - BACKGROUND: Polyomavirus-associated nephropathy is associated with high risk of
      kidney allograft loss. Whether the cause of native end-stage renal disease
      influences the risk of BK infection is unclear. METHODS: A retrospective, single
      center study of 2741 adult kidney transplant recipients between 1994 and 2014 was
      performed. Recipients had end-stage renal disease due to polycystic kidney
      disease (PKD, n = 549), diabetes mellitus (DM, n = 947), hypertension (HTN, n =
      442), or glomerulonephritis (GN, n = 803). RESULTS: A total of 327 recipients
      (12%) developed post-transplant BK viremia over a median follow-up time of 5
      years. The incidence rate of BK viremia was lowest in patients with PKD (1.46 per
      100 person-years) compared to other causes of ESRD (DM = 2.06, HTN = 2.65, and GN
      = 2.01 per 100 person-years). A diagnosis of PKD was associated with a lower risk
      of post-transplant BK viremia (adjusted HR (95% CI) = 0.67 (0.48-0.95), P =
      0.02). BK nephropathy was significantly less common in patients with PKD (0.21
      per 100 person-years) compared to those with HTN (0.80 per 100 person-years, P <=
      0.001). Among patients with PKD, the risk of BK viremia was lower in patients
      with nephrectomy, compared to those without nephrectomy (adjusted HR (95% CI) =
      0.42 (0.19-0.92), P < 0.05). CONCLUSION: ESRD due to PKD is associated with a
      lower risk of post-transplant BK infection. The renal tubular epithelial cells in
      PKD are unique; they are in a proliferative but non-differentiated state. Whether
      this characteristic of renal tubular epithelial cells alters the BK viral
      reservoir or replication in PKD patients warrants further study.

PMID- 30102821
TI  - Platelet count and platelet-lymphocyte ratio as prognostic markers for head and
      neck squamous cell carcinoma: A meta-analysis.
AB  - BACKGROUND: Thrombocytosis is associated with the prognosis of various types of
      cancer. The purpose of this study was to quantify the prognostic impact of
      platelet count and platelet-lymphocyte ratio (PLR) in head and neck squamous cell
      carcinoma (HNSCC). METHODS: We systematically searched electronic databases and
      identified articles reporting an association between platelet count or PLR and
      HNSCC prognosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) for
      overall survival (OS) were extracted, and the pooled HRs were estimated using
      random effect models. RESULTS: Eight studies that enrolled 4096 patients and 9
      studies that enrolled 2327 patients were included in the platelet count and PLR
      analyses, respectively. A platelet count greater than the cutoff value was
      associated with poor OS (HR 1.81; 95% CI 1.16-2.82) and any PLR greater than the
      cutoff value was associated with poor OS (HR 1.64; 95% CI 1.13-2.37). CONCLUSION:
      Elevated platelet count and PLR are associated with poor prognosis in patients
      with HNSCC.

PMID- 30102822
TI  - Rhodium-Catalyzed [4+2+1] Cycloaddition of In Situ Generated Ene/Yne-Ene-Allenes
      and CO.
AB  - Reported herein is the first rhodium-catalyzed [4+2+1] cycloaddition of in situ
      generated ene/yne-ene-allenes and CO to synthesize challenging seven-membered
      carbocycles fused with five-membered rings. This reaction is designed based on
      the 1,3-acyloxy migration of ene/yne-ene-propargyl esters to ene/yne-ene-allenes,
      followed by oxidative cyclization, CO insertion, and reductive elimination to
      form the final [4+2+1] cycloadducts. The possible competing [4+1], [4+2], and
      [2+2+1] cycloadditions were disfavored, making the present reaction an efficient
      way to access functionalized 5/7 rings.

PMID- 30102823
TI  - Stent grafts in patients with carotid blowout syndrome: Outcome and antiplatelet
      therapy in preventive versus emergency cases.
AB  - BACKGROUND: Carotid blowout syndrome due to tumor infiltration, fistulas, and
      therapy-related necrosis can occur as late as years after the treatment.
      Reporting our experiences with preventive and acute treatment with stent grafts
      and discussing different ways of antiplatelet therapy. METHODS: We reviewed all
      patients between 2010 and 2016 who underwent stent graft placement and analyzed
      outcome, complications, and antiplatelet regime. RESULTS: Seventeen patients were
      treated in 24 sessions (n = 7 threatened, n = 5 imminent, and n = 12 acute
      bleeding). The antiplatelet regime covered the entire range from aspirin only to
      loading doses of aspirin/clopidogrel, perioperative heparin, and
      aspirin/clopidogrel for 12 months followed by lifelong aspirin. Rare
      complications were not associated with the preprocedural or periprocedural but
      were associated with the postprocedural antiplatelet regime. CONCLUSION: Most
      complications of stent graft implantations due to a carotid blowout syndrome
      occur postprocedurally: rare thrombotic events are linked to not taking a
      medication and frequent rebleedings may be reduced by an earlier reduction of
      dual-antiplatelet to mono-antiplatelet therapy.

PMID- 30102824
TI  - Decreased gastrostomy tube incidence and weight loss after transoral robotic
      surgery for low- to intermediate-risk oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: Functional outcomes after treatment for oropharyngeal squamous cell
      carcinoma (SCC) are increasingly prioritized. The purpose of this study was to
      investigate the incidence of gastrostomy tube placement and weight loss in
      patients with oropharyngeal SCC who may be eligible for either transoral robotic
      surgery (TORS) or nonsurgical management. METHODS: We conducted a retrospective
      review of previously untreated T1 to T2 and N0 to N2b oropharyngeal SCC to
      determine the rates of gastrostomy tube placement and weight loss according to
      Common Terminology Criteria for Adverse Events (CTCAE) criteria. Multivariate
      regression models were fit to compare these end points between groups. RESULTS:
      Two hundred twenty-three patients were included, comprised of 66 patients who
      underwent TORS and 157 patients who underwent (chemo)radiation. Thirty-two
      (48.5%) of the TORS patients received adjuvant radiation. On multivariate
      analysis, patients treated nonsurgically were 10.6 times and 8.1 times more
      likely to receive a gastrostomy tube and experience greater than CTCAE grade 1
      weight loss, respectively. CONCLUSION: In selected patients with oropharyngeal
      SCC, TORS may help avoid critical weight loss and gastrostomy tube placement in
      the acute treatment period.

PMID- 30102825
TI  - Donor Dopamine Does Not Affect Liver Graft Survival: Evidence of Safety From a
      Randomized Controlled Trial.
AB  - Treatment of donation after brain death (DBD) donors with low-dose dopamine
      improves the outcomes after kidney and heart transplantation. This study
      investigates the course of liver allografts from multiorgan donors enrolled in
      the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov
      identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were
      randomly assigned to receive low-dose dopamine. Dopamine was infused at 4
      MUg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5
      hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at
      32 European centers. Donors and recipients of both groups were very similar in
      baseline characteristics. Pretransplant laboratory Model for End-Stage Liver
      Disease score was not different in recipients of a dopamine-treated versus
      untreated graft (18 +/- 8 versus 20 +/- 8; P = 0.12). Mean cold ischemia time was
      10.6 +/- 2.9 versus 10.1 +/- 2.8 hours (P = 0.24). No differences occurred in
      biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of
      hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early
      retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary
      nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus
      14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at
      2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and
      65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor
      pretreatment with dopamine has no short-term or longterm effects on outcome after
      LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the
      standard of care in hemodynamically stable DBDs.

PMID- 30102826
TI  - Responses of leaf C:N:P stoichiometry to water supply in the desert shrub
      Zygophyllum xanthoxylum.
AB  - Based on the elemental composition of major biochemical molecules associated with
      different biological functions, the 'growth rate hypothesis' proposed that
      organisms with a higher growth rate would be coupled to lower C:N, especially
      lower C:P and N:P ratios. However, the applicability of the growth rate
      hypothesis for plants is unclear, especially for shrubs growing under different
      water supply. We performed an experiment with eight soil moisture levels (soil
      water content: 4%, 6%, 8%, 13%, 18%, 23%, 26% and 28%) to evaluate the effects of
      water availability on leaf C:N:P stoichiometry in the shrub Zygophyllum
      xanthoxylum. We found that leaves grew slowly and favored accumulation of P over
      C and N under both high and low water supply. Thus, leaf C:P and N:P ratios were
      unimodally related to soil water content, in parallel with individual leaf area
      and mass. As a result, there were significant positive correlations between leaf
      C:P and N:P with leaf growth (u). Our result that slower-growing leaves had lower
      C:P and N:P ratios does not support the growth rate hypothesis, which predicted a
      negative association of N:P ratio with growth rate, but it is consistent with
      recent theoretical derivations of growth-stoichiometry relations in plants, where
      N:P ratio is predicted to increase with increasing growth for very low growth
      rates, suggesting leaf growth limitation by C and N rather than P for drought and
      water saturation.

PMID- 30102827
TI  - Corals sustain growth but not skeletal density across the Florida Keys Reef Tract
      despite ongoing warming.
AB  - Through the continuous growth of their carbonate skeletons, corals record
      information about past environmental conditions and their effect on colony
      fitness. Here, we characterize century-scale growth records of inner and outer
      reef corals across ~200 km of the Florida Keys Reef Tract (FKRT) using skeletal
      cores extracted from two ubiquitous reef-building species, Siderastrea siderea
      and Pseudodiploria strigosa. We find that corals across the FKRT have sustained
      extension and calcification rates over the past century but have experienced a
      long-term reduction in skeletal density, regardless of reef zone. Notably, P.
      strigosa colonies exhibit temporary reef zone-dependent reductions in extension
      rate corresponding to two known extreme temperature events in 1969-1970 and 1997
      1998. We propose that the subtropical climate of the FKRT may buffer corals from
      chronic growth declines associated with climate warming, though the significant
      reduction in skeletal density may indicate underlying vulnerability to present
      and future trends in ocean acidification.

PMID- 30102828
TI  - Mechanistic insight on the combined effect of albumin and hydrogen peroxide on
      surface oxide composition and extent of metal release from Ti6Al4V.
AB  - The titanium-aluminium (6 wt%)-vanadium (4 wt%) (Ti6Al4V) alloy is widely used as
      an orthopedic and dental implant material due to its high corrosion resistance in
      such environments. The corrosion resistance is usually determined by means of
      electrochemical methods, which may not be able to detect other chemical surface
      reactions. Literature findings report a synergistic effect of the combination of
      the abundant protein albumin and hydrogen peroxide (H2 O2 ) on the extent of
      metal release and corrosion of Ti6Al4V. The objectives of this study were to gain
      further mechanistic insight on the interplay of H2 O2 and albumin on the metal
      release process of Ti6Al4V with special focus on (1) kinetics and (2) H2 O2 and
      albumin concentrations. This was accomplished mainly by metal release and surface
      oxide composition investigations, which confirmed the combined effect of H2 O2
      and albumin on the metal release process, although not detectable by
      electrochemical open circuit potential measurements. A concentration of 30 mM H2
      O2 induced substantial changes in the surface oxide characteristics, an oxide
      which became thicker and enriched in aluminum. Bovine serum albumin (BSA) seemed
      to be able to deplete this aluminum content from the outermost surface or at
      least to delay its surface enrichment. This effect increased with increased BSA
      concentration, and for time periods longer than 24 h. This study hence suggests
      that short-term (accelerated) corrosion resistance measurements are not
      sufficient to predict potential health effects of Ti6Al4V alloys since also
      chemical dissolution mechanisms play a large role for metal release, possibly in
      a synergistic way. (c) 2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part
      B, 2018.

PMID- 30102829
TI  - Transcriptome analysis of papillary thyroid cancer harboring telomerase reverse
      transcriptase promoter mutation.
AB  - BACKGROUND: Telomerase reverse transcriptase (TERT) promoter mutations have
      recently been identified as an important prognostic factor in thyroid cancer.
      Studies suggest that TERT may have noncanonical functions beyond telomere
      maintenance. METHODS: Clinicopathological information and transcriptome data for
      papillary thyroid carcinoma (PTC) samples were obtained from The Cancer Genome
      Atlas (TCGA). Propensity score matching was performed to adjust for potential
      confounding variables between the TERT promoter wild-type group and the mutant
      group. Gene expression data of 36 patients in the mutant group were systemically
      compared to those of 72 patients in the wild-type group. RESULTS: Tumors with
      TERT promoter mutations had a higher TERT expression. Pathways central to DNA
      damage responses and cell cycle regulation were significantly enriched among 888
      upregulated genes. Transporter and metabolic activities were overrepresented
      among 799 downregulated genes. There was no difference in the expression of most
      of the thyroid differentiation genes. CONCLUSION: The TERT promoter mutations
      were associated with proliferative and metabolic alterations in PTC.

PMID- 30102830
TI  - Medrobotics Flex transanal excision of a rectal gastrointestinal stromal tumour:
      first video of the transanal Flex robot used in a human - a video vignette.

PMID- 30102831
TI  - Predictors of graft function after parathyroid autotransplantation during thyroid
      surgery.
AB  - BACKGROUND: The purpose of this study was to identify predictors associated with
      graft function after parathyroid autotransplantation during thyroid surgery.
      METHODS: One hundred fifty patients who underwent thyroid surgery with
      parathyroid autotransplantation were enrolled prospectively. During surgery, the
      misresected or devascularized parathyroid gland was autografted in the
      brachioradialis muscle of the forearm. Parathyroid hormone (PTH) levels in both
      arms were measured regularly after surgery. Patient age, sex, extent of surgery,
      and postoperative serum calcium levels were recorded. RESULTS: Graft function was
      documented in 115 patients (76.7%). Univariate analysis revealed that graft
      function had a significant association with lower serum calcium level 1 day after
      surgery. The cutoff point was 2.11 mmol/L, which was confirmed by a receiver
      operating characteristic (ROC) curve. CONCLUSION: Low serum calcium levels in the
      early postoperative period may stimulate a functional recovery in an autografted
      parathyroid gland. Therefore, a moderate calcium supplement strategy was
      recommended for patients who underwent parathyroid autotransplantation during the
      early stage after total thyroidectomy.

PMID- 30102832
TI  - Symptom burden in adults with thyroid cancer.

PMID- 30102833
TI  - Electrospun fibroin/polyurethane hybrid meshes: Manufacturing, characterization,
      and potentialities as substrates for haemodialysis arteriovenous grafts.
AB  - Several attempts made so far to combine silk fibroin and polyurethane, in order
      to prepare scaffolds encompassing the bioactivity of the former with the
      elasticity of the latter, suffer from critical drawbacks concerning industrial
      and clinical applicability (e.g., separation of phases upon processing, use of
      solvents unaddressed by the European Pharmacopoeia, and use of degradable
      polyurethanes). Overcoming these limitations, in this study, we report the
      successful blending of regenerated silk fibroin with a medical-grade, non
      degradable polyurethane using formic acid and dichloromethane, and the
      manufacturing of hybrid, semi-degradable electrospun tubular meshes with
      different ratios of the two materials. Physicochemical analyses demonstrated the
      maintenance of the characteristic features of fibroin and polyurethane upon
      solubilization, blending, electrospinning, and postprocessing with ethanol or
      methanol. Envisioning their possible application as semidegradable substrates for
      haemodialysis arteriovenous grafts, tubular meshes were further characterized,
      showing submicrometric fibrous morphologies, tunable mechanical properties,
      permeability before and after puncture in the same order of magnitude as
      commercial grafts currently used in the clinics. Results demonstrate the
      potential of this material for the development of hybrid, new-generation vascular
      grafts with disruptive potential in the field of in situ tissue engineering. (c)
      2018 Wiley Periodicals, Inc. J. Biomed. Mater. Res. Part B, 2018.

PMID- 30102835
TI  - Rapid Fabrication of Chip-Based Physiometers for Neurobehavioral Toxicity Assays
      Using Rotifers Brachionus calyciflorus.
AB  - An increased interest in implementations of Lab-on-a-Chip (LOC) technologies for
      in-situ analysis of multicellular metazoan model organisms and their embryonic
      stages demands development of new prototyping techniques. Due to size of
      multicellular organisms the fabrication of soft-lithography molds requires
      features with high aspect ratios as well as deposition of layers with significant
      thicknesses. This makes them time consuming and difficult to fabricate using
      conventional photolithography techniques. In this work we describe development of
      a rapid technique capable of generating thick films achieved with high viscosity
      SU-8 and used in fabricating master templates for high aspect ratio micro- and
      mesofluidic devices. The cost effective and rapid method eliminated the need for
      multiple spin coating cycles as well as edge bead artifacts while preserving low
      surface roughness and superior surface uniformity. Due to elimination of spin
      coating steps, typically constrained to clean room facilities, the new method
      allows to significantly reduce microfabrication costs. We have utilized the
      prototyping technique to develop proof-of-concept chip-based devices capable of
      effectively caging freshwater rotifers Brachionus calyciflorus for high
      definition video-microscopy analysis. The combination of time-resolved video
      microscopy and chip-based physiometers enabled us to demonstrate new applications
      for neurobehavioral assays utilizing non-invasive sub-lethal end-points.

PMID- 30102834
TI  - Retinal vascular density in multiple sclerosis: a 1-year follow-up.
AB  - BACKGROUND AND PURPOSE: Vascular pathology is increasingly acknowledged as a risk
      factor for multiple sclerosis (MS). Vascular density (VD) is reduced in the eyes
      of patients with MS on optical coherence tomography (OCT) angiography. We
      performed a 1-year prospective study to estimate VD variations over time and
      possible clinical correlates. METHODS: A total of 50 patients with MS underwent
      spectral domain-OCT and OCT angiography at baseline and after 1-year follow-up.
      Mixed-effect linear regression models were used to assess variations of each OCT
      measure and its relation to treatment and clinical outcomes. RESULTS: We observed
      an increase in parafovea VD (coefficient, 1.147; 95% confidence interval, 0.081
      2.214; P = 0.035). Reduction in parafovea VD was associated with increase in
      Expanded Disability Status Scale score (coefficient, -0.969; 95% confidence
      interval, -1.732/-0.207; P = 0.013). CONCLUSIONS: Retinal VD can improve over
      time in MS, particularly in patients experiencing disease stability. Longer
      follow-up, inclusion of early MS cases and combination with conventional markers
      of MS severity (i.e. brain atrophy) are needed to better define VD as a potential
      new biomarker.

PMID- 30102836
TI  - Phosphatized tungsten-metabolizing coccoid microbes interpreted from oil shale of
      an Eocene lake, Green River Formation, Utah, USA.
AB  - Microscopic globular structures have been observed in some beds of oil shale from
      eastern Utah. These beds comprise carbonate-dominated mud that is interlaminated
      with variably thick and continuous organic-rich layers. Collectively they are
      enriched in phosphorus, REEs, and actinides. The beds are considered of
      lacustrine origin and assigned to the Eocene Green River Formation. The globules
      themselves are of microcrystalline carbonate fluorapatite (MUCFA), often contain
      concentric internal structures, and usually group together in clusters of up to
      80, possibly more. Detailed SEM and microprobe analyses have revealed tungsten
      (W) to be almost exclusively associated with the globular clusters found within
      the more organic-rich laminae, often at concentrations of over 200 ppm, two
      orders of magnitude above shale standards. The globular structures are present in
      freshly cut sections where they occasionally grade into a MUCFA matrix cement.
      This, together with the draping of the clusters by stringers of organic matter
      that would have accumulated in the Eocene lake, confirms that the structures are
      not a contaminant. The limited range of sizes and globular shapes is consistent
      with the morphology of coccoidal bacteria: Concentric internal structures may
      represent remnants of the nucleoid and cell wall. Paired concentric structures
      may indicate cell division (reproduction) processes were occurring until
      mineralization. The phosphate mineralization itself may have been promoted by
      release of phosphate from the stressed cells, bringing porewaters to
      supersaturation, or by the cells acting as nucleation sites. The recording of
      trace amounts of W almost exclusively in globular clusters preserved in the most
      organic-rich stringers (anoxia prone) further suggests facultative use of W
      enzymes in a microbial metabolism. Combined, their context, morphology, and
      indication of biogenic process are strong evidence that the structures are
      fossilized (phosphatized) microbes, possibly sulfate-reducing bacteria, or
      methanogenic archaea.

PMID- 30102837
TI  - Involvement of lipid transfer proteins in resistance against a non-host powdery
      mildew in Arabidopsis thaliana.
AB  - Non-specific lipid transfer proteins (LTPs) are involved in the transport of
      lipophilic compounds to the cuticular surface in epidermal cells and in the
      defence against pathogens. The role of glycophosphatidylinositol (GPI)-anchored
      LTPs (LTPGs) in resistance against non-host mildews in Arabidopsis thaliana was
      investigated using reverse genetics. Loss of either LTPG1, LTPG2, LTPG5 or LTPG6
      increased the susceptibility to penetration of the epidermal cell wall by
      Blumeria graminis f. sp. hordei (Bgh). However, no impact on pre-penetration
      defence against another non-host mildew, Erysiphe pisi (Ep), was observed. LTPG1
      was localized to papillae at the sites of Bgh penetration. This study shows that,
      in addition to the previously known functions, LTPGs contribute to pre-invasive
      defence against certain non-host powdery mildew pathogens.

PMID- 30102838
TI  - Hot Off the Press: Validation of the Pediatric NEXUS II Head Computed Tomography
      Decision Instrument for Selective Imaging of Pediatric Patients with Blunt Head
      Trauma.
AB  - This is a validation of a preplanned secondary analysis of the NEXUS II Head
      computed tomography (CT) decision instrument, focusing on the pediatric
      population. A total of 1,018 patients less than 18 years old, who underwent head
      CT imaging for blunt head trauma, were included. The decision instrument
      correctly identified all patient (27/27) who required neurosurgical intervention
      and 48 of 49 patients who had clinically significant head injury on CT imaging.

PMID- 30102839
TI  - What are the immunological and clinical implications of microchimerism?

PMID- 30102840
TI  - Integrative Photoreduction of CO2 with Subsequent Carbonylation: Photocatalysis
      for Reductive Functionalization of CO2.
AB  - Efficient conversion of CO2 into fuels and chemicals with solar energy would be
      promising, but also faces great challenge. In this context, we describe the
      photoreductive functionalization of CO2 to construct new C-C, C-N, and C-O bonds
      through the respective Pd-catalyzed Suzuki carbonylation, aminocarbonylation, and
      alkoxycarbonylation of aryl iodides with CO in situ generated through the
      photoreduction of CO2 . This protocol opens up an alternative avenue for CO2
      utilization by harnessing solar energy.

PMID- 30102841
TI  - Effect of 1- and 2-Month High-Dose Alpha-Linolenic Acid Treatment on 13 C-Labeled
      Alpha-Linolenic Acid Incorporation and Conversion in Healthy Subjects.
AB  - SCOPE: The study aims at identifying 1) the most sensitive compartment among
      plasma phospholipids, erythrocytes, and LDL for studying alpha-linolenic acid
      (ALA) conversion, and 2) whether ALA incorporation and conversion is saturable
      after administration of 13 C-labeled ALA-rich linseed oil (LO). The effect of a
      daily intake of 7 g nonlabeled LO (>43% w/w ALA) for 1 month after bolus
      administration of 7 g 13 C-labeled LO on day 1, and for 2 months after bolus
      administration of 7 g 13 C-labeled LO on day 1 and day 29 on 13 C-ALA
      incorporation and conversion into its higher homologs is investigated in healthy
      volunteers. METHODS AND RESULTS: Incorporation and conversion of LO-derived 13 C
      labeled ALA is quantified by applying compartmental modeling. After bolus
      administration, a fractional conversion of approximately 30% from 13 C-ALA to 13
      C-DHA is calculated as reflected by the LDL compartment. Treatment with LO for 8
      weeks induces a mean reduction of 13 C-ALA conversion to 13 C-DHA by 48% as
      reflected by the LDL compartment, and a mean reduction of the 13 C-ALA
      incorporation into LDL by 46%. CONCLUSION: A 2-month dietary intake of a high
      dose of LO is sufficient to reach saturation of ALA incorporation into LDL
      particles, which are responsible for ALA distribution in the body.

PMID- 30102842
TI  - A generic framework for spatial quantitative risk assessments of infectious
      diseases: Lumpy skin disease case study.
AB  - The increase in availability of spatial data and the technological advances to
      handle such data allow for subsequent improvements in our ability to assess risk
      in a spatial setting. We provide a generic framework for quantitative risk
      assessments of disease introduction that capitalizes on these new data. It can be
      adopted across multiple spatial scales, for any pathogen, method of transmission
      or location. The framework incorporates the risk of initial infection in a
      previously uninfected location due to registered movement (e.g., trade) and
      unregistered movement (e.g., daily movements of wild animals). We discuss the
      steps of the framework and the data required to compute it. We then outline how
      this framework is applied for a single pathway using lumpy skin disease as a case
      study, a disease which had an outbreak in the Balkans in 2016. We calculate the
      risk of initial infection for the rest of Europe in 2016 due to trade. We perform
      the risk assessment on 3 spatial scales-countries, regions within countries and
      individual farms. We find that Croatia (assuming no vaccination occurred) has the
      highest mean probability of infection, with Italy, Hungary and Spain following.
      Including import detection of infected trade does reduce risk but this reduction
      is proportionally lower for countries with highest risk. The risk assessment
      results are consistent across the spatial scales, while in addition, at the finer
      spatial scales, it highlights specific areas or individual locations of countries
      on which to focus surveillance.

PMID- 30102843
TI  - Perivascular adipose tissue: A new possible tissue augmenting coronary
      vasodilatation in response to acute hypoxia.

PMID- 30102845
TI  - Undergraduate ear, nose and throat training: How do we inspire the next
      generation? Response to author.

PMID- 30102844
TI  - Dual targeting: Combining costimulation blockade and bortezomib to permit kidney
      transplantation in sensitized recipients.
AB  - Previous evidence suggests that a homeostatic germinal center (GC) response may
      limit bortezomib desensitization therapy. We evaluated the combination of
      costimulation blockade with bortezomib in a sensitized non-human primate kidney
      transplant model. Sensitized animals were treated with bortezomib, belatacept,
      and anti-CD40 mAb twice weekly for a month (n = 6) and compared to control
      animals (n = 7). Desensitization therapy-mediated DSA reductions approached
      statistical significance (P = .07) and significantly diminished bone marrow PCs,
      lymph node follicular helper T cells, and memory B cell proliferation. Graft
      survival was prolonged in the desensitization group (P = .073). All control
      animals (n = 6) experienced graft loss due to antibody-mediated rejection (AMR)
      after kidney transplantation, compared to one desensitized animal (1/5). Overall,
      histological AMR scores were significantly lower in the treatment group (n = 5)
      compared to control (P = .020). However, CMV disease was common in the
      desensitized group (3/5). Desensitized animals were sacrificed after long-term
      follow-up with functioning grafts. Dual targeting of both plasma cells and
      upstream GC responses successfully prolongs graft survival in a sensitized NHP
      model despite significant infectious complications and drug toxicity. Further
      work is planned to dissect underlying mechanisms, and explore safety concerns.

PMID- 30102846
TI  - Synthesis and in vitro Evaluation of ADAM10 and ADAM17 Highly Selective
      Bioimaging Probes.
AB  - A disintegrin and metalloproteinase (ADAMs) are membrane-bound metalloproteases
      responsible for the ectodomain shedding of various transmembrane proteins and
      play important roles in multiple relevant biological processes. Their altered
      expression is involved in several pathological conditions, and in particular
      ADAM10 or ADAM17 overexpression is found in various forms of cancer. To better
      understand how they are regulated in the cellular context, it is useful to
      visualize the specific ADAMs pathway by means of molecular imaging techniques.
      For this purpose, we synthesized bioactive fluorescent probes suitable for cell
      imaging and that are able to specifically target ADAM10 or ADAM17. Two previously
      developed ADAM17- and ADAM10-selective inhibitors were chosen for conjugation,
      respectively, to a Cy5.5 dye and to Cy5.5 and FITC dyes. Herein we also report
      the synthesis of a gold-labeled compound as an additional bioimaging probe for
      ADAM10. The newly synthesized ligands were found to be active in vitro on human
      recombinant ADAM10 and/or ADAM17, showing IC50 values in the nanomolar range and
      a good selectivity over matrix metalloproteinases (MMPs). Finally, these newly
      developed probes were successfully used for ADAMs staining on different lymphoma
      cell lines and lymph node mesenchymal stromal cells.

PMID- 30102847
TI  - Cardiovascular sequelae of the sleep apnoea syndrome: Sex, stress and therapeutic
      strategies.

PMID- 30102848
TI  - Emergence of African Swine Fever in China, 2018.

PMID- 30102849
TI  - Identification of metabolites of evobrutinib in rat and human hepatocytes by
      using ultra-high performance liquid chromatography coupled with diode array
      detector and Q Exactive Orbitrap tandem mass spectrometry.
AB  - Evobrutinib is a highly selective inhibitor of Bruton's tyrosine kinase (BTK)
      which may be clinically effective in treating certain autoimmune diseases. The
      purpose of the present study was to investigate the metabolism of evobrutinib in
      rat and human hepatocytes. Evobrutinib was incubated with rat and human
      hepatocytes at 37 degrees C for 2 hours after which the samples were analyzed by
      ultra-high performance liquid chromatography with diode array detection and Q
      Exactive Orbitrap tandem mass spectrometry (UPLC-DAD-Q Exactive Orbitrap-MS). The
      acquired data were processed by MetWorksTM software using mass effect filter and
      background subtraction functions. Under these conditions, 23 metabolites were
      detected and their identities proposed. Among these metabolites, M13 and M15 were
      identified by comparison of their retention times, accurate masses, and fragment
      ions with those of authentic reference standards. The metabolic pathways of
      evobrutinib were proposed accordingly. Our results demonstrated that evobrutinib
      was metabolized via hydroxylation, hydrolysis, O-dealkylation, glucuronidation,
      and GSH conjugation. Species-related metabolic differences between rat and human
      hepatocytes were observed. M1-M4 were rat-specific metabolites. M13 (hydroxyl
      evobrutinib) was the major metabolite whereas M15 (evobrutinib-diol) was a minor
      metabolite in rat hepatocytes. On the other hand, M6, M11, M16, M17, and M19 were
      human-specific metabolites. M15 was the most abundant metabolite whereas M13 was
      the minor metabolite in human hepatocytes. This study provides preliminary
      information regarding the metabolism of evobrutinib that may be helpful in
      understanding the pharmacology of evobrutinib.

PMID- 30102850
TI  - Ticks infesting dogs in rural communities of Yucatan, Mexico and molecular
      diagnosis of rickettsial infection.
AB  - Rickettsial infection in dog-associated ticks in three rural communities of
      Yucatan, Mexico was investigated using qPCR and nested PCR assays. A total of 319
      dogs were studied and ticks samples were collected. A total of 170 dogs were
      infested with ticks (frequency of 53.4%). Overall, 1,380 ticks representing seven
      species were collected: Amblyomma mixtum, A. ovale, A. parvum, A. cf.
      oblongoguttatum, Ixodes affinis, Rhipicephalus microplus, and R. sanguineus sensu
      lato. The most abundant species was R. sanguineus s.l. with a mean intensity of
      7.4 ticks/host. Dogs in the communities of Chan San Antonio and Yaxcheku were
      2.84 and 2.41 times more likely to be infected with R. sanguineus compared with
      Sucopo (p < 0.05). Adult pools of A. mixtum, A. parvum, I. affinis, R. microplus,
      and A. c.f. oblongoguttatum were negative to E. chaffeensis, E. ewingii, A.
      phagocytophilum, and R. rickettsii. However, pools of R. sanguineus s.l. adults
      and A. ovale adults, as well as nymphs of Amblyomma spp. were positive to E.
      canis. Sequencing analysis of the nested PCR products amplifying the 16S rRNA
      gene fragment of E. canis confirmed the results and revealed 100% identity with
      sequences of E. canis. This is the first report worldwide of E. canis infection
      in A. ovale by PCR. This finding does not necessarily indicate that A. ovale is a
      competent vector of E. canis because pathogen transmission of this specific tick
      to a naive dog remains to be documented. This study documented that different
      tick species parasitize dogs in Yucatan, Mexico, where R. sanguineus s.l., A.
      ovale, and nymphs of Amblyomma spp. were shown to be infected with E. canis.
      These findings highlight the need for control strategies against tick
      infestations in dogs to prevent the risk of tick-borne disease transmission among
      companion animal and probably human populations.

PMID- 30102851
TI  - Evolutionary and genotypic analyses of global porcine epidemic diarrhea virus
      strains.
AB  - Porcine epidemic diarrhea virus (PEDV), which re-emerged in China in October
      2010, has spread rapidly worldwide. Detailed analyses of the complete genomes of
      different PEDV strains are essential to understand the relationships among re
      emerging and historic strains worldwide. Here, we analysed the complete genomes
      of 409 strains from different countries, which were classified into five subgroup
      strains (i.e., GI-a, GI-b, GII-a, GII-b, and GII-c). Phylogenetic study of
      different genes in the PEDV strains revealed that the newly discovered subgroup
      GII-c exhibited inconsistent topologies between the spike gene and other genes.
      Furthermore, recombination analysis indicated that GII-c viruses evolved from a
      recombinant virus that acquired the 5' part of the spike gene from the GI-a
      subgroup and the remaining genomic regions from the GII-a subgroup. Molecular
      clock analysis showed that divergence of the GII-c subgroup spike gene occurred
      in April 2010, suggesting that the subgroup originated from recombination events
      before the PEDV re-emergence outbreaks. Interestingly, Ascaris suum, a large
      roundworm occurring in pigs, was found to be an unusual PEDV host, providing
      potential support for cross-host transmission. This study has significant
      implications for understanding ongoing global PEDV outbreaks and will guide
      future efforts to develop effective preventative measures against PEDV.

PMID- 30102852
TI  - Combinatorial Synthesis and High-Throughput Characterization of Fe-V-O Thin-Film
      Materials Libraries for Solar Water Splitting.
AB  - The search for suitable materials for solar water splitting is addressed with
      combinatorial material science methods. Thin film Fe-V-O materials libraries were
      synthesized using combinatorial reactive magnetron cosputtering and subsequent
      annealing in air. The design of the libraries comprises a combination of large
      compositional gradients (from Fe10V90O x to Fe79V21O x) and thickness gradients
      (from 140 to 425 nm). These material libraries were investigated by high
      throughput characterization techniques in terms of composition, structure,
      optical, and photoelectrochemical properties to establish correlations between
      composition, thickness, crystallinity, microstructure, and photocurrent density.
      Results show the presence of the Fe2V4O13 phase from ~11 to 42 at. % Fe (toward
      low-Fe region) and the FeVO4 phase from ~37 to 79 at. % Fe (toward Fe-rich
      region). However, as a third phase, Fe2O3 is present throughout the compositional
      gradients (from low-Fe to Fe-rich region). Material compositions with increasing
      crystallinity of the FeVO4 phase show enhanced photocurrent densities (~160 to
      190 MUA/cm2) throughout the thickness gradients whereas compositions with the
      Fe2V4O13 phase show comparatively low photocurrent densities (~28 MUA/cm2). The
      band gap energies of Fe-V-O films were inferred from Tauc plots. The highest
      photocurrent density of ~190 MUA/cm2 was obtained for films with ~54 to 66 at. %
      Fe for the FeVO4 phase with ~2.04 eV for the indirect and ~2.80 eV for the direct
      band gap energies.

PMID- 30102853
TI  - Bionic Single-Electrode Electronic Skin Unit Based on Piezoelectric
      Nanogenerator.
AB  - Moravec's paradox shows that low-level sensorimotor skills are more difficult
      than high-level reasoning in artificial intelligence and robotics. So simplifying
      every sensing unit on electronic skin is critical for endowing intelligent robots
      with tactile and temperature sense. The human nervous system is characterized by
      efficient single-electrode signal transmission, ensuring the efficiency and
      reliability of information transmission under big data conditions. In this work,
      we report a sensor based on a single-electrode piezoelectric nanogenerator
      (SPENG) by electrospun polyvinylidene fluoride (PVDF) nanofibers that can realize
      steady-state sensing of pressure integrating cold/heat sensing on a single unit.
      Piezoelectric signals appear as square wave signals, and the thermal-sensing
      signals appear as pulse signals. Therefore, the two signals can be acquired by a
      single unit simultaneously. The SPENG overcomes the shortcoming of electronic
      skins based on a single-electrode triboelectric nanogenerator (STENG), which can
      sense only dynamic movement and cannot sense temperature variations. The new
      sensor configuration uses a capacitor instead of the STENG's ground wire as a
      potential reference, allowing it to be used for truly autonomous robots. At the
      same time, the traditional advantages of polymer piezoelectric materials, such as
      flexibility, transparency, and self-powered advantages, have also been preserved.

PMID- 30102854
TI  - Structural and Atropisomeric Factors Governing the Selectivity of Pyrimido
      benzodiazipinones as Inhibitors of Kinases and Bromodomains.
AB  - Bromodomains have been pursued intensively over the past several years as
      emerging targets for the development of anticancer and anti-inflammatory agents.
      It has recently been shown that some kinase inhibitors are able to potently
      inhibit the bromodomains of BRD4. The clinical activities of PLK inhibitor BI
      2536 and JAK2-FLT3 inhibitor TG101348 have been attributed to this unexpected
      polypharmacology, indicating that dual-kinase/bromodomain activity may be
      advantageous in a therapeutic context. However, for target validation and
      biological investigation, a more selective target profile is desired. Here, we
      report that benzo[e]pyrimido-[5,4- b]diazepine-6(11H)-ones, versatile ATP-site
      directed kinase pharmacophores utilized in the development of inhibitors of
      multiple kinases, including several previously reported kinase chemical probes,
      are also capable of exhibiting potent BRD4-dependent pharmacology. Using a dual
      kinase-bromodomain inhibitor of the kinase domains of ERK5 and LRRK2, and the
      bromodomain of BRD4 as a case study, we define the structure-activity
      relationships required to achieve dual kinase/BRD4 activity, as well as how to
      direct selectivity toward inhibition of either ERK5 or BRD4. This effort resulted
      in identification of one of the first reported kinase-selective chemical probes
      for ERK5 (JWG-071), a BET selective inhibitor with 1 MUM BRD4 IC50 (JWG-115), and
      additional inhibitors with rationally designed polypharmacology (JWG-047, JWG
      069). Co-crystallography of seven representative inhibitors with the first
      bromodomain of BRD4 demonstrate that distinct atropisomeric conformers recognize
      the kinase ATP-site and the BRD4 acetyl lysine binding site, conformational
      preferences supported by rigid docking studies.

PMID- 30102856
TI  - Ab Initio Finite Temperature Auxiliary Field Quantum Monte Carlo.
AB  - We present an ab initio auxiliary field quantum Monte Carlo method for studying
      the electronic structure of molecules, solids, and model Hamiltonians at finite
      temperature. The algorithm marries the ab initio phaseless auxiliary field
      quantum Monte Carlo algorithm known to produce high accuracy ground state
      energies of molecules and solids with its finite temperature variant, long used
      by condensed matter physicists for studying model Hamiltonian phase diagrams, to
      yield a phaseless, ab initio finite temperature method. We demonstrate that the
      method produces internal energies within chemical accuracy of exact
      diagonalization results across a wide range of temperatures for H2O (STO-3G), C2
      (STO-6G), the one-dimensional hydrogen chain (STO-6G), and the multiorbital
      Hubbard model. Our method effectively controls the phase problem through
      importance sampling, often even without invoking the phaseless approximation,
      down to temperatures at which the systems studied approach their ground states
      and may therefore be viewed as exact over wide temperature ranges. This technique
      embodies a versatile tool for studying the finite temperature phase diagrams of a
      plethora of systems whose properties cannot be captured by a Hubbard U term
      alone. Our results moreover illustrate that the severity of the phase problem for
      model Hamiltonians far exceeds that for many molecules at all of the temperatures
      studied.

PMID- 30102855
TI  - Native Chemical Ligation for Cross-Linking of Flower-Like Micelles.
AB  - In this study, native chemical ligation (NCL) was used as a selective cross
      linking method to form core-cross-linked thermosensitive polymeric micelles for
      drug delivery applications. To this end, two complementary ABA triblock
      copolymers having polyethylene glycol (PEG) as midblock were synthesized by atom
      transfer radical polymerization (ATRP). The thermosensitive poly
      isopropylacrylamide (PNIPAM) outer blocks of the polymers were copolymerized with
      either N-(2-hydroxypropyl)methacrylamide-cysteine (HPMA-Cys), P(NIPAM- co-HPMA
      Cys)-PEG-P(NIPAM- co-HPMA-Cys) (PNC) or N-(2-hydroxypropyl)methacrylamide
      ethylthioglycolate succinic acid (HPMA-ETSA), P(NIPAM- co-HPMA-ETSA)-PEG-P(NIPAM-
      co-HPMA-ETSA) (PNE). Mixing of these polymers in aqueous solution followed by
      heating to 50  degrees C resulted in the formation of thermosensitive flower-like
      micelles. Subsequently, native chemical ligation in the core of micelles resulted
      in stabilization of the micelles with a Z-average of 65 nm at body temperature.
      Decreasing the temperature to 10  degrees C only affected the size of the
      micelles (increased to 90 nm) but hardly affected the polydispersity index (PDI)
      and aggregation number ( Nagg) confirming covalent stabilization of the micelles
      by NCL. CryoTEM images showed micelles with an uniform spherical shape and dark
      patches close to the corona of micelles were observed in the tomographic view.
      The dark patches represent more dense areas in the micelles which coincide with
      the higher content of HPMA-Cys/ETSA close to the PEG chain revealed by the
      polymerization kinetics study. Notably, this cross-linking method provides the
      possibility for conjugation of functional molecules either by using the thiol
      moieties still present after NCL or by simply adjusting the molar ratio between
      the polymers (resulting in excess cysteine or thioester moieties) during micelle
      formation. Furthermore, in vitro cell experiments demonstrated that fluorescently
      labeled micelles were successfully taken up by HeLa cells while cell viability
      remained high even at high micelle concentrations. These results demonstrate the
      potential of these micelles for drug delivery applications.

PMID- 30102858
TI  - A Small-Molecule Compound Has Anti-influenza A Virus Activity by Acting as a
      ''PB2 Inhibitor".
AB  - With regular influenza epidemics and the prevalence of drug-resistant influenza
      virus strains, it is extremely crucial to develop effective and low-toxicity anti
      influenza A virus drugs that act on conserved sites of novel targets. Here, we
      found a new anti-influenza virus compound, 1,3-dihydroxy-6-benzo[ c]chromene
      (D715-2441), from a library of 8026 small-molecule compounds by cell-based MTT
      assay and explored the underlying mechanisms. Our results revealed that D715-2441
      possessed antiviral activities against multiple subtypes of influenza A viruses
      (IAVs) strains, including H1N1, H5N1, H7N9, H3N2, the clinical isolate 690 (H3),
      and oseltamivir-resistant strains with the H274Y NA mutation, and suppressed the
      early steps in the virus replication cycle. Further mechanistic studies indicated
      that D715-2441 clearly inhibited viral polymerase activity and directly
      influenced the location of the PB2 protein. Moreover, binding affinity analyses
      confirmed that D715-2441 bound specifically to the PB2cap protein. Further,
      protein sequence alignment and a computer-aided molecular docking indicated that
      highly conserved amino acid residues in the cap-binding pocket of PB2cap were
      possible binding sites for D715-2441, which indicates that D715-2441 might be
      employed as a cap-binding competitor. Moreover, the combination of D715-2441 and
      zanamivir possessed a remarkable synergistic antiviral effect, with an FICI value
      of 0.40. In conclusion, these results strongly suggest that D715-2441 has
      potential as a promising candidate against IAV infection. More importantly, our
      work offers novel options for the strategic development of PB2cap inhibitors of
      IAV.

PMID- 30102857
TI  - Peripheral Membrane Proteins Facilitate Nanoparticle Binding at Lipid Bilayer
      Interfaces.
AB  - Molecular understanding of the impact of nanomaterials on cell membranes is
      critical for the prediction of effects that span environmental exposures to
      nanoenabled therapies. Experimental and computational studies employing
      phospholipid bilayers as model systems for membranes have yielded important
      insights but lack the biomolecular complexity of actual membranes. Here, we
      increase model membrane complexity by incorporating the peripheral membrane
      protein cytochrome c and studying the interactions of the resulting membrane
      systems with two types of anionic nanoparticles. Experimental and computational
      studies reveal that the extent of cytochrome c binding to supported lipid
      bilayers depends on anionic phospholipid number density and headgroup chemistry.
      Gold nanoparticles functionalized with short, anionic ligands or wrapped with an
      anionic polymer do not interact with silica-supported bilayers composed solely of
      phospholipids. Strikingly, when cytochrome c was bound to these bilayers,
      nanoparticles functionalized with short anionic ligands attached to model
      biomembranes in amounts proportional to the number of bound cytochrome c
      molecules. In contrast, anionic polymer-wrapped gold nanoparticles appeared to
      remove cytochrome c from supported lipid bilayers in a manner inversely
      proportional to the strength of cytochrome c binding to the bilayer; this
      reflects the removal of a weakly bound pool of cytochrome c, as suggested by
      molecular dynamics simulations. These results highlight the importance of the
      surface chemistry of both the nanoparticle and the membrane in predicting nano
      bio interactions.

PMID- 30102859
TI  - Changes of Chemical Composition and Hemicelluloses Structure in Differently Aged
      Bamboo ( Neosinocalamus affinis) Culms.
AB  - To study the differences in chemical composition analysis and spatial
      distribution of young Neosinocalamus affinis bamboo, we used the methods of
      standard of National Renewable Energy Laboratory and confocal Raman microscopy,
      respectively. It was found that the acid-soluble lignin and acid-insoluble lignin
      content showed an inverse relationship with the increasing bamboo age. Raman
      analysis revealed that Raman signal intensity of lignin in both the secondary
      cell wall and the compound middle lamella regions showed a similar increase trend
      with growth of bamboo. In addition, eight hemicellulosic fractions were obtained
      by successively treating holocellulose of the 2-, 4-, 8-, and 12-month-old
      Neosinocalamus affinis bamboo culms with DMSO and alkaline solution. The ratio of
      arabinose to xylose of hemicelluloses was increased with the growth of bamboo. FT
      IR and NMR analyses revealed that DMSO-soluble hemicelluloses of young bamboo
      culms are mainly composed of highly substituted xylans and beta-d-glucans.

PMID- 30102860
TI  - Oil Sands Derived Naphthenic Acids Are Oxidative Uncouplers and Impair Electron
      Transport in Isolated Mitochondria.
AB  - Naphthenic acids (NAs) are predominant compounds in oil sands influenced waters.
      These acids cause numerous acute and chronic effects in fishes. However, the
      mechanism of toxicity underlying these effects has not been fully elucidated. Due
      to their carboxylic acid moiety and the reported disruption of cellular
      bioenergetics by similar structures, we hypothesized that NAs would uncouple
      mitochondrial respiration with the resultant production of reactive oxygen
      species (ROS). Naphthenic acids were extracted and purified from 17-year-old oil
      sands tailings waters yielding an extract of 99% carboxylic acids with 90%
      fitting the classical O2-NA definition. Mitochondria were isolated from rainbow
      trout liver and exposed to different concentrations of NAs. Mitochondrial
      respiration, membrane potential, and ROS emission were measured using the
      Oroboros fluorespirometry system. Additionally, mitochondrial ROS emission and
      membrane potential were evaluated with real-time flow cytometry. Results showed
      NAs uncoupled oxidative phosphorylation, inhibited respiration, and increased ROS
      emission. The effective concentration (EC50) and inhibition concentration (IC50)
      values for the end points measured ranged from 21.0 to 157.8 mg/L, concentrations
      similar to tailings waters. For the same end points, EC10/IC10 values ranged from
      11.8 to 66.7 mg/L, approaching concentrations found in the environment. These
      data unveil mechanisms underlying effects of NAs that may contribute to adverse
      effects on organisms in the environment.

PMID- 30102861
TI  - Bioavailability of Pyrene Associated with Different Types of Protein Compounds:
      Direct Evidence for Its Uptake by Daphnia magna.
AB  - The protein-like dissolved organic matter (DOM) is ubiquitous in aquatic
      environments. However, the bioavailability of protein-like DOM-associated
      hydrophobic organic compounds (HOCs) is not well-understood, and in particular,
      the direct evidence of their uptake by organisms is scarce. In the present work,
      tryptone (2000 Da), bovine serum albumin (BSA; 66 000 Da), and phycocyanin (120
      000 Da) were chosen as model protein-like DOM, which were labeled by commercial
      fluorescein (cy5) to investigate the uptake mechanisms of protein compound
      associated pyrene (a typical HOC) by Daphnia magna. The pyrene concentration in
      the tissues except the gut and immobilization of D. magna were detected to
      calculate the bioavailable fraction of protein compound-associated pyrene when
      the freely dissolved pyrene concentration was controlled through passive dosing
      devices. The results demonstrated that the tryptone could permeate cellular
      membrane and directly enter the tissues of  D. magna from the exposure solutions,
      whereas BSA and phycocyanin might indirectly enter the tissues from the gut. A
      part of pyrene associated with protein compounds was bioavailable to D. magna;
      the order of their bioavailable fractions was trypone (54.6-58.1%) > phycocyanin
      (21.6-32.8%) > BSA (17.7-26.8%). The difference was principally related to the
      uptake mechanisms of pyrene associated with different types of protein. This work
      suggests that the protein compound-associated HOCs should be considered to
      evaluate the bioavailability and eco-environmental hazard of HOCs in natural
      waters.

PMID- 30102862
TI  - One-Pot Synthesis of NiCo2S4 Hollow Spheres via Sequential Ion-Exchange as an
      Enhanced Oxygen Bifunctional Electrocatalyst in Alkaline Solution.
AB  - The oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) are
      considered to be cornerstones of many energy conversion and storage technologies.
      It is difficult studying high-performance nonprecious materials as cost-effective
      bifunctional electrocatalysts for both the OER and ORR in future practical
      applications. In this study, NiCo2S4 hollow spheres (NiCo2S4 HSs) were fabricated
      via an effective and facile one-pot "green" approach in an N, N-dimethylformamide
      ethylene glycol binary solution. The obtained NiCo2S4 HSs had a high specific
      surface area as well as numerous active sites and showed a remarkable catalytic
      performance and durability toward both the OER and ORR in an alkaline
      electrolyte. For the ORR, NiCo2S4 HSs exhibited a positive half-wave potential of
      0.80 V and demonstrated outstanding stability and enhanced methanol tolerance.
      For the OER, NiCo2S4 HSs presented a low overpotential (400 mV) at a current
      density of 10 mA cm-2, small Tafel slope, and excellent stability in 0.1 M KOH.
      Moreover, regarding the overall electrocatalytic activity, the potential
      difference of NiCo2S4 HSs was 0.83 V, surpassing that of NiCo2S4 nanoparticles,
      binary counterparts (CoS, NiS), and most highly active bifunctional catalysts
      described in the literature. The superior catalytic performance of NiCo2S4 HSs is
      mainly ascribed to its unique hollow structure, which increases molecular
      diffusion and adsorption, as well as the synergistic effect of Ni and Co, which
      offers richer redox reaction sites. Importantly, this strategy may facilitate the
      design and preparation of excellent bifunctional nonprecious metal
      electrocatalysts in various domains.

PMID- 30102863
TI  - Transport Mechanisms of Butyrate Modified Nanoparticles: Insight into "Easy
      Entry, Hard Transcytosis" of Active Targeting System in Oral Administration.
AB  - The intestinal epithelium constitutes a major barrier for orally delivered
      nanoparticles (NPs). Although surface ligand modification can increase cellular
      uptake of NPs, the transepithelial transport of active targeting NPs is
      relatively limited. The phenomenon is described as "easy entry, hard
      transcytosis". However, underlying mechanisms and potential solutions of this
      phenomenon are unclear. Here, butyrate modified polyethylene glycol coated NPs
      (Bu-PEG NPs) were chosen as the model active targeting NPs. Transport mechanism
      studies were performed to get a better understanding of intracellular trafficking
      and exocytosis fate. Results showed that after active binding to monocarboxylate
      transporter-1 (MCT-1), Bu-PEG NPs went through endolysosomal pathways,
      endoplasmic reticulum/Golgi recycling routes, and microtubule-dependent shuttling
      within Caco-2 cells. Then a larger proportion of Bu-PEG NPs was exocytosed from
      apical side. Notably, increasing the basal expression of MCT-1 by leptin
      facilitated basal exocytosis and transcytosis of Bu-PEG NPs, which confirmed that
      enhanced receptor recognition could promote "basal exit". In addition to the
      effect of receptor recognition, surface properties also influenced the
      bidirectional exocytosis of Bu-PEG NPs. When surface hydrophobicity increased, Bu
      PEG NPs were dominantly exocytosed from basal membrane. Hence, two strategies may
      help to overcome "hard transcytosis" of active targeting NPs. One is to enhance
      their affinity with basal membrane by reinforcing the receptor-ligand
      interaction; the other is to weaken apical exocytosis by optimizing surface
      hydrophobicity. Thereby, this study might provide important implications for the
      rational design of NPs to further increase transepithelial transport efficiency.

PMID- 30102864
TI  - Use of 111In-Hexavalent Lactoside for Liver Reserve Estimation in Rodents with
      Thioacetamide-Induced Hepatic Fibrosis.
AB  - Many biochemical tests detecting the presence of liver disease are not liver
      specific and may be abnormal in nonhepatic conditions. The asialoglycoprotein
      receptor (ASGPR) is a hepatocyte-specific receptor for Gal/GalNAc-terminated
      glycopeptide or glycoprotein. The number of these receptors decreases in patients
      with chronic liver diseases. Here, we aimed to evaluate the use of 111In
      hexavalent lactoside, a known ASGPR imaging biomarker, as a more sensitive probe
      to detect small changes in liver reserve in animal models of chronic liver
      injury. Thioacetamide (TAA) treatment via intraperitoneal injection every 2 days
      in BALB/c mice continued for 1, 2, 3, or 4 months. The liver fibrosis stages were
      determined by Sirius Red staining and were based on the METAVIR classification
      method. Serum transaminase enzymes (alanine transaminase (ALT) and aspartate
      transaminase (AST)), alkaline phosphatase, albumin, and bilirubin were measured
      using a FUJI FDC3500 i/s analyzer. The ASGPR staining was performed by
      immunohistocytochemical stain. The percentages of fibrosis and ASGPR were
      calculated using ImageJ software after collagen staining and anti-ASGPR staining,
      respectively. A nanoSPECT/CT was used for molecular imaging and liver uptake
      measurement. We observed fibrosis grades of F0-F1 in mice treated with TAA for 1
      month, F2 in mice treated for 2 months, F3-F4 in mice treated for 3 months, and
      F4 in mice treated for 4 months. The levels of ALT and albumin were not
      significantly different in the TAA groups from those in the controls. Although
      the average levels of AST, alkaline phosphatase, and bilirubin in the TAA groups
      were different from those in the control group, there was little difference
      between TAA groups. More sensitive distinctions among TAA groups were detected in
      111In-hexavalent lactoside uptake of ASGPR, ASGPR staining, and fibrosis % than
      when using the conventional AST, ALT, albumin, alkaline phosphatase, and
      bilirubin tests. The absorption and distribution of 111In-hexavalent lactoside
      were lower in the chronic hepatitis models than the normal controls. The liver
      reserves measured by 111In-hexavalent lactoside uptake were 71.7 +/- 7.5% and
      50.9 +/- 5.6% after 1 and 2 months, respectively, of TAA treatment. As an ASGPR
      biomarker, 111In-hexavalent lactoside has higher sensitivity than traditional
      liver function tests and collagen stain to provide more objective data for
      evaluating compensated cirrhosis or changes in liver damage. ASGPR staining can
      reflect the regenerated hepatocytes, but the need for a biopsy limits its use.
      111In-hexavalent lactoside measurement is comparable with ASGPR staining, which
      suggests that 111In-hexavalent lactoside measurement will be more useful as a
      practical, noninvasive test of chronic liver injury.

PMID- 30102866
TI  - Meeting Report: The 61st Annual Meeting of the CSMB, Membrane Proteins in Health
      and Disease.
AB  - This is a synopsis of the 61st Annual Meeting of the CSMB, Membrane Proteins in
      Health and Disease.

PMID- 30102865
TI  - Splenic blood-flow response following myocardial infarction in rat.
AB  - During physiological stress (e.g., exercise, hypoxia), blood flow is shunted to
      specific anatomical regions to protect critical organs; yet, splenic blood flow
      in these circumstances remains to be investigated. Despite being classically
      viewed as a non-critical organ, recent experimental and epidemiological evidence
      suggests the spleen plays a significant role in cardiovascular pathophysiology.
      We hypothesized that splenic blood flow is prioritized in the development of
      heart failure (i.e., chronic state of reduced cardiac output). Five-week-old male
      Wistar rats were randomized for either myocardial infarction (MI; n = 58) or sham
      (n = 56) surgery. At 2, 5, and 9 weeks post-surgery, Doppler ultrasound
      measurements of the splenic, left renal, left common carotid, and left femoral
      arteries were performed. Cardiac function was assessed at all time points using
      echocardiography and at 9 weeks post-surgery using invasive hemodynamic analysis.
      Splenic and cerebral blood flow was preferentially maintained at 9 weeks post-MI,
      whereas blood flow to the lower limb and kidney were reduced. Spleen size
      increased by 5 weeks post-MI and remained elevated. Splenic blood flow was
      maintained in conditions of decreased cardiac output, when other tissues showed
      decreased blood flow. The maintenance of blood flow in the face of decreased
      cardiac output indicates that splenic function is being prioritized during heart
      failure.

PMID- 30102867
TI  - The discovery of proteases and intramembrane proteolysis.
AB  - Proteases carry out a wide variety of physiological functions. This review
      presents a brief history of protease research, starting with the original
      discovery of pepsin in 1836. Following the path of time, we revisit how proteases
      were originally classified based on their catalytic mechanism and how chemical
      and crystallographic studies unravelled the mechanism of serine proteases.
      Ongoing research on proteases addresses their biological roles, small molecule
      inhibitors for therapeutic uses, and protein engineering to modify their
      activities. The discovery of intramembrane proteases is more recent, beginning
      with the discovery of site-2 protease in 1997. Since then, different mechanistic
      classes of intramembrane proteases have been characterized, and many of these act
      in regulated intramembrane proteolysis in signaling pathways. Furthermore, the
      rhomboid intramembrane proteases were discovered by genetic and biochemical
      experiments in Drosophila and then in human cells. Research on the intramembrane
      proteases is expanding, as their biological importance is recognized.

PMID- 30102868
TI  - Bayesian Multiparameter Evidence Synthesis to Inform Decision Making: A Case
      Study in Metastatic Hormone-Refractory Prostate Cancer.
AB  - In health technology assessment, decisions are based on complex cost
      effectiveness models that require numerous input parameters. When not all
      relevant estimates are available, the model may have to be simplified.
      Multiparameter evidence synthesis combines data from diverse sources of evidence,
      which results in obtaining estimates required in clinical decision making that
      otherwise may not be available. We demonstrate how bivariate meta-analysis can be
      used to predict an unreported estimate of a treatment effect enabling
      implementation of a multistate Markov model, which otherwise needs to be
      simplified. To illustrate this, we used an example of cost-effectiveness analysis
      for docetaxel in combination with prednisolone in metastatic hormone-refractory
      prostate cancer. Bivariate meta-analysis was used to model jointly available data
      on treatment effects on overall survival and progression-free survival (PFS) to
      predict the unreported effect on PFS in a study evaluating docetaxel with
      prednisolone. The predicted treatment effect on PFS enabled implementation of a 3
      state Markov model comprising stable disease, progressive disease, and dead
      states, while lack of the estimate restricted the model to a 2-state model (with
      alive and dead states). The 2-state and 3-state models were compared by
      calculating the incremental cost-effectiveness ratio (which was much lower in the
      3-state model: L22,148 per quality-adjusted life year gained compared to L30,026
      obtained from the 2-state model) and the expected value of perfect information
      (which increased with the 3-state model). The 3-state model has the advantage of
      distinguishing surviving patients who progressed from those who did not progress.
      Hence, the use of advanced meta-analytic techniques allowed obtaining relevant
      parameter estimates to populate a model describing disease pathway in more detail
      while helping to prevent valuable clinical data from being discarded.

PMID- 30102869
TI  - Ten-Year Risk Factors for Inferior Knee Injury and Osteoarthritis Outcome Score
      After Anterior Cruciate Ligament Reconstruction: A Study of 874 Patients From the
      Swedish National Knee Ligament Register.
AB  - BACKGROUND: Factors relating to the patient and anterior cruciate ligament (ACL)
      reconstruction may help to identify prognostic factors of long-term outcome after
      reconstruction. PURPOSE: To determine 10-year risk factors for inferior knee
      function after ACL reconstruction. STUDY DESIGN: Cohort study; Level of evidence,
      2. METHODS: Prospectively collected data from the Swedish National Knee Ligament
      Register were extracted for patients who underwent ACL reconstruction between
      January 2005 and December 2006. Patients who had no data at the 10-year follow-up
      for the Knee injury and Osteoarthritis Outcome Score (KOOS) were excluded.
      Multivariable proportional odds regression modeling was used to assess 10-year
      patient- and surgery-related risk factors across all the KOOS subscales and the
      KOOS4 (mean score of 4 subscales: pain, knee-related symptoms, function in sport
      and recreation, and knee-related quality of life). RESULTS: A total of 874 (41%)
      patients were included (male, 51.5%; median age at the time of ACL
      reconstruction, 27.5 years [range, 11.2-61.5 years]). An increase in the severity
      of concomitant articular cartilage injuries resulted in a reduced KOOS on 4
      subscales (odds ratio, 0.64-0.80; P < .05). A higher preoperative KOOS pain score
      increased the odds of a higher score on the pain, symptoms, and sport subscales
      and the KOOS4. In addition, a higher preoperative body mass index was a
      significant risk factor for lower scores on 3 KOOS subscales and the KOOS4. No
      patient- or surgery-related predictor was significant across all KOOS subscales.
      CONCLUSION: This 10-year risk factor analysis identified several factors that can
      affect long-term knee function after ACL reconstruction. Most risk factors were
      related to preoperative patient-reported outcome and potentially modifiable. On
      the other hand, most of the surgery-related risk factors were nonmodifiable.
      Nevertheless, this information may be helpful to physicians and physical
      therapists counseling patients on their expectations of outcome after ACL
      reconstruction.

PMID- 30102870
TI  - Perfectionism and training performance: The mediating role of other-approach
      goals.
AB  - Recent research found perfectionistic strivings to predict performance in a novel
      basketball task among novice basketball players. The current study builds on this
      research by examining whether this is also the case for performance in a familiar
      basketball training task among experienced basketball players, and whether
      achievement goals mediated any observed relationships. Perfectionistic strivings,
      perfectionistic concerns, and 3 * 2 achievement goals were assessed prior to
      basketball training performance in 90 basketball players (mean age 20.9 years).
      Regression analyses showed that perfectionistic strivings predicted better
      performance. Furthermore, mediation analyses showed that other-approach goals
      (e.g. beliefs that one should and can outperform others) accounted for this
      relationship. The findings suggest that perfectionistic strivings may predict
      better performance in both novel and familiar athletic contexts. In addition,
      beliefs about the importance and ability to outperform others may explain this
      relationship.

PMID- 30102871
TI  - Sitting cross-legged for 30 minutes alters lower limb shear stress pattern but
      not flow-mediated dilation or arterial stiffness.
AB  - Prolonged sitting decreases lower limb endothelial function via sustained
      reductions in mean shear rate. We tested whether 30 minutes of sitting cross
      legged differentially impacts superficial femoral artery shear rate pattern, flow
      mediated dilation (FMD) and leg pulse-wave velocity (PWV) compared to sitting
      flat-footed. Sitting cross-legged attenuated the reduction in mean and antegrade
      shear rate and increased arterial pressure compared to sitting flat-footed.
      Superficial femoral artery FMD and leg PWV were unaltered following either
      sitting position.

PMID- 30102872
TI  - Longer-term effects of minimalist shoes on running performance, strength and bone
      density: A 20-week follow-up study.
AB  - This study investigated whether male runners improve running performance, running
      economy, ankle plantar flexor strength, and alter running biomechanics and lower
      limb bone mineral density when gradually transitioning to using minimalist shoes
      for 100% of weekly running. The study was a planned follow-up of runners (n = 50)
      who transitioned to minimalist or conventional shoes for 35% of weekly structured
      training in a previous 6-week randomised controlled trial. In that trial, running
      performance and economy improved more with minimalist shoes than conventional
      shoes. Runners in each group were instructed to continue running in their
      allocated shoe during their own preferred training programme for a further 20
      weeks while increasing allocated shoe use to 100% of weekly training. At the 20
      week follow-up, minimalist shoes did not affect performance (effect size: 0.19; p
      = 0.218), running economy (effect size: <= 0.24; p >= 0.388), stride rate or
      length (effect size: <= 0.12; p >= 0.550), foot strike (effect size: <= 0.25; p
      >= 0.366), or bone mineral density (effect size: <= 0.40; p >= 0.319). Minimalist
      shoes increased plantar flexor strength more than conventional shoes when runners
      trained with greater mean weekly training distances (shoe*distance interaction: p
      = 0.036). After greater improvements with minimalist shoes during the initial six
      weeks of a structured training programme, increasing minimalist shoe use from 35%
      to 100% over 20 weeks, when runners use their own preferred training programme,
      did not further improve performance, running economy or alter running
      biomechanics and lower limb bone mineral density. Minimalist shoes improved
      plantar flexor strength more than conventional shoes in runners with greater
      weekly training distances.

PMID- 30102873
TI  - Morphology-Based Analysis of Myoblasts for Prediction of Myotube Formation.
AB  - The development of new drugs depends on the efficiency of drug screening.
      Phenotype-based screening has attracted interest due to its considerable potency
      for the discovery of first-in-class drugs. In general, fluorescently labeled
      imagery is the leading technique for phenotype-based screening; however, there
      are growing requirements to understand total culture profiles, which are unclear
      after end-point assays. In this study, we demonstrate that morphology-based
      cellular evaluation of unlabeled cells is an efficient approach to evaluate
      myotube formation assays. One of our aims was to study the myogenic
      differentiation process in C2C12 cells to discern the differences between
      cellular responses to different medium conditions (serum concentrations and
      insulin dosages). Our results show that predictive morphological profiles that
      strongly correlate with myogenic differentiation can be generated from myotube
      images, even in the confluent stage. The differentiation rate after 14 days can
      be quantitatively predicted with the highest accuracy by means of images taken on
      days 0-11.5. In addition, for the application of our morphology-based cellular
      evaluation, the effect of cyclic guanosine monophosphate (cGMP) on myogenic
      differentiation was analyzed. Our results show that the quantitated morphological
      profile from these images can be an effective descriptor for analysis of the
      myotube-recovering effect of cGMP.

PMID- 30102874
TI  - The effect of acute caffeine ingestion on upper body anaerobic exercise and
      cognitive performance.
AB  - The current study examined the effect of acute caffeine ingestion on mean and
      peak power production during upper body Wingate test (WANT) performance, rating
      of perceived exertion, readiness to invest effort and cognitive performance.
      Using a double-blind design, 12 males undertook upper body WANTs, following
      ingestion of caffeine (5 mg*kg-1) or placebo. Pre-substance ingestion, 60 mins
      post substance ingestion and post exercise participants completed measures of
      readiness to invest physical and mental effort and cognitive performance. Peak
      power was significantly higher (P = .026), fatigue index greater (P = .02) and
      rating of perceived exertion lower (P = .025) in the presence of caffeine.
      Readiness to invest physical effort was also higher (P = .016) in the caffeine
      condition irrespective of time point (pre, 60 mins post ingestion and post
      exercise). Response accuracy for incongruent trials on the Flanker task was
      superior in the presence of caffeine (P = .006). There was a significant
      substance * time interaction for response speed in both congruent and incongruent
      conditions (both P = .001) whereby response speeds were faster at 60 mins post
      ingestion and post exercise in the caffeine condition, compared to placebo. This
      is the first study to examine the effects of caffeine ingestion on this modality
      of exercise and suggests that caffeine ingestion significantly enhances peak
      power, readiness to invest physical effort, and cognitive performance during WANT
      performance.

PMID- 30102876
TI  - Measuring early childhood development in Brazil: validation of the Caregiver
      Reported Early Development Instruments (CREDI).
AB  - OBJECTIVE: The present study aims to analyze the psychometric properties and
      general validity of the Caregiver Reported Early Development Instruments (CREDI)
      short form for the population-level assessment of early childhood development for
      Brazilian children under age 3. METHOD: The study analyzed the acceptability,
      test-retest reliability, internal consistency and discriminant validity of the
      CREDI short-form tool. The study also analyzed the concurrent validity of the
      CREDI with a direct observational measure (Inter-American Development Bank's
      Regional Project on Child Development Indicators; PRIDI). The full sample
      includes 1,265 Brazilian caregivers of children from 0 to 35 months (678 of which
      comprising an in-person sample and 587 an online sample). RESULTS: Results from
      qualitative interviews suggest overall high rates of acceptability. Most of the
      items showed adequate test-retest reliability, with an average agreement of 84%.
      Cronbach's alpha suggested adequate internal consistency/inter-item reliability
      (alpha>0.80) for the CREDI within each of the six age groups (0-5, 6-11, 12-17,
      18-23, 24-29 and 30-35 months of age). Multivariate analyses of construct
      validity showed that a significant proportion of the variance in CREDI scores
      could be explained by child gender and family characteristics, most importantly
      caregiver-reported cognitive stimulation in the home (p<0.0001). Regarding
      concurrent validity, scores on the CREDI were significantly correlated with
      overall PRIDI scores within the in-person sample at r=0.46 (p<0.001).
      CONCLUSIONS: The results suggested that the CREDI short form is a valid,
      reliable, and acceptable measure of early childhood development for children
      under the age of 3 years in Brazil.

PMID- 30102878
TI  - Therapeutic Efficacy of Cranioplasty After Decompressive Craniectomy for
      Traumatic Brain Injury: A Retrospective Study.
AB  - PURPOSE: Autologous bone removed at the time of decompressive craniectomy (DC) is
      always the first choice for cranioplasty. The aim of this study was to evaluate
      the therapeutic efficacy of cranioplasty after DC by measuring the changes in the
      Functional Independence Measure (FIM) score, as well as to draw a comparison with
      the pre-cranioplasty FIM score and to evaluate the differences in the outcomes of
      cases managed by 2 methods: autologous bone (group I) or titanium mesh (group
      II). MATERIALS AND METHODS: We included 47 patients (36 male and 11 female
      patients) who underwent unilateral cranioplasty after DC for traumatic brain
      injury at our institute from 2008 to 2017 in this analytical single-institution
      retrospective study. The primary binary predictor variable was cranioplasty
      reconstructive material (autologous bone or mesh). The primary outcome variable
      of interest was increased, decreased, or unchanged FIM score. The secondary
      outcome variables included evaluation of immediate complications. The Mann
      Whitney U test was used to evaluate differences between scores. RESULTS: Group I
      (n = 26) underwent cranioplasty using autologous bone flap, whereas group II (n =
      21) underwent cranioplasty using dynamic titanium mesh. Increases in FIM scores
      on the motor function subscale for group I (P = .01278) and group II (P = .00112)
      were statistically significant. Increases in FIM scores on the cognition subscale
      for group I (P = .17384) and group II (P = .9492) were statistically
      insignificant. Evaluation of the primary outcome variable (ie, increased,
      decreased, or unchanged FIM scores) and secondary outcome variables (ie,
      immediate complications) showed a statistically insignificant difference between
      the 2 groups with respect to improvement (P = .51). CONCLUSIONS: This study
      showed that cranioplasty, irrespective of the reconstructive material, after DC
      in patients with traumatic brain injury results in a significant functional
      improvement apart from form and esthetics.

PMID- 30102877
TI  - Do Implant Surgical Guides Allow an Adequate Zone of Keratinized Tissue for
      Flapless Surgery?
AB  - PURPOSE: A major advantage of guided implant surgery using 3-dimensionally
      printed guides is the ability to perform accurate flapless surgery. A drawback of
      a flapless technique is the inability to manipulate soft tissue to ensure
      sufficient gingiva around the implant. The purpose of this study was to determine
      how often flapless surgery using surgical guides results in less than 2 mm of
      keratinized tissue surrounding the implant. MATERIALS AND METHODS: This
      retrospective analysis included 27 maxillary and 27 mandibular implant sites that
      underwent treatment planning for implant-guided surgery using 3Shape Implant
      Studio (3Shape, Copenhagen, Denmark). Intraoral scan images were used to measure
      the width of the keratinized tissue on the buccal aspect of each implant site in
      both arches and the lingual aspect in the mandibular arch. Three examiners
      measured the amount of buccal and lingual keratinized tissue in millimeters at
      each implant site. Analysis of variance (P < .05) and correlation coefficients
      were used to determine statistically significant differences in keratinized
      tissue among sites. RESULTS: No statistically significant difference was found
      either between the widths of buccal keratinized tissue in the maxillary anterior
      (4.06 +/- 1.42 mm) and posterior (4.93 +/- 2.54 mm) areas (P = .293) or between
      the amounts of buccal and lingual keratinized tissue in the mandible (P = .995).
      The keratinized tissue width in the maxillary buccal area was significantly
      different (4.48 +/- 2.04 mm) from that in the mandibular posterior buccal (1.98
      +/- 1.41 mm) and lingual (1.98 +/- 1.23 mm) areas (P < .001). Over 77% of
      maxillary implant sites had greater than 3 mm of gingiva, and just over 20% had
      sufficient gingiva in the mandible. CONCLUSIONS: Adequate keratinized tissue was
      found in most of the planned maxillary implant sites, whereas most of the
      mandibular posterior implant sites had inadequate keratinized tissue. Therefore,
      elevation of a flap to preserve and reposition existing keratinized tissue around
      implants should be considered when planning to use tooth-borne surgical guides in
      the posterior mandible.

PMID- 30102879
TI  - Is Gender Associated With Success in Academic Oral and Maxillofacial Surgery?
AB  - PURPOSE: Several studies of surgical specialties have shown disparities in
      measures of research productivity and academic rank between female and male
      surgeons. The purpose of this work was to measure the role of surgeon gender in
      academic success in oral and maxillofacial surgery. MATERIALS AND METHODS: We
      performed a cross-sectional study of full-time academic oral and maxillofacial
      surgeons (OMSs) in the United States as of June 2017. The primary study variable
      was surgeon gender (male or female). The primary outcome variable was research
      productivity assessed using 2 different parameters: 1) h index (number of
      publications h with at least h citations each) and 2) academic rank. The other
      study variables were demographic characteristics potentially related to the
      outcome measures. Descriptive, bivariate, and regression statistics were
      computed. RESULTS: The study sample comprised 306 full-time academic OMSs, 53
      (17.3%) of whom were women. On average, female OMSs had shorter academic careers
      (mean time since completion of training, 11.0 +/- 8.2 years for female OMSs vs
      22.0 +/- 14.1 years for male OMSs; P < .001). There were no other significant
      differences between male and female OMSs regarding the secondary measures (P >=
      .23). Male OMSs had a higher mean h index than female OMSs (7.1 +/- 8.6 vs 5.1 +/
      7.9, P = .01). Academic rank was statistically significantly different between
      female and male OMSs, with a greater proportion of higher ranks seen in male OMSs
      (P = .001). After adjustment for career length and other confounders or effect
      modifiers, gender was not an independent predictor of the h index or academic
      rank (P >= .22). CONCLUSIONS: Although female surgeons represent a minority of
      full-time academic OMSs, academic success measured using research productivity
      and academic rank was not associated with gender.

PMID- 30102880
TI  - Idiopathic Condylar Resorption: A Survey and Review of the Literature.
AB  - PURPOSE: Idiopathic condylar resorption (ICR) is a relatively uncommon condition.
      Its diagnosis, etiology, and management options are controversial. Furthermore,
      it is difficult for 1 provider to collect a large cohort of ICR patients to
      develop a statistically significant study of these concerns. Therefore, the
      purpose of this study was to survey experienced temporomandibular joint (TMJ)
      surgeons who have managed ICR cases relative to these concerns, as well as review
      the management outcome literature. MATERIALS AND METHODS: SurveyMonkey (Palo
      Alto, CA) was used to canvas the 88 international TMJ surgeons on the TMJ
      Concepts (Ventura, CA) InterNetwork. This network connects a group of surgeons
      across the world who consistently perform TMJ surgery. The intent was to provide
      a global snapshot of the demographic, epidemiologic, diagnostic workup, and
      outcome data related to the management of ICR cases. RESULTS: The surveys from
      surgeons who did not respond to all 12 questions were not included in the
      results. After application of the exclusion criteria, complete data on a cohort
      of 100 patients were obtained and used for the study. A history of hormonal
      imbalance was reported in only 10% of patients; however, 42 of 94 women were
      reportedly taking birth control pills presumably affecting their menstrual
      cycles. The most common reason for consultation was Class II malocclusion (98% of
      patients). Treatment modalities varied and included orthodontics, orthotics, TMJ
      total joint replacement, orthognathic surgery, and disc repositioning.
      CONCLUSIONS: ICR management proved to be controversial among the surveyed
      surgeons. Multiple treatment options have been described in the literature,
      including medical management, orthognathic surgery only, TMJ and orthognathic
      surgery, and total joint prosthesis reconstruction. Long-term, controlled,
      multicenter clinical studies should be developed to evaluate outcomes of all
      nonsurgical and surgical management options for the ICR patient.

PMID- 30102881
TI  - Different roles of insulin receptor a and b in maintaining blood glucose
      homeostasis in zebrafish.
AB  - An inability of insulin to signal glycolysis and gluconeogenesis would largely
      result in type 2 diabetes. In this study, the physiological roles of zebrafish
      insulin receptor a and b in maintaining blood glucose homeostasis were
      characterized. We observed that, though blood glucose in insra-/- fish and insrb
      /- fish were comparable with the control siblings at 0 h postprandium (hpp), the
      most evident hyperglycemia have been observed in insra-/- fish from 1 hpp to 3
      hpp. A mild increase of blood glucose in insrb-/- fish has been seen only at 1.5
      hpp. The down-regulated expressions of glycolytic enzymes were observed in insra
      /- fish and insrb-/- fish liver and muscle, together with the significantly
      decreased activities or concentrations of glycolytic enzymes. These results
      suggest that both Insra and Insrb were critical in glycolysis. Intriguingly, the
      up-regulated expressions of gluconeogenic enzymes, pck1 and g6pca.1, along with
      the elevated enzyme activities, were observed in insra-/- fish liver at 1 hpp and
      1.5 hpp. Compared with the control fish, the elevated plasma insulin and lowered
      phosphorylated AKT were observed in insra-/- fish and insrb-/- fish, suggesting
      that there is an insulin resistance in insra-/- fish and insrb-/- fish. The
      increased levels of both transcriptions of foxo1a and Foxo1a protein abundance in
      the insra-/- fish liver have been found. When insra-/- fish treated with the
      Foxo1 inhibitor, the postprandial blood glucose levels could be normalized,
      accompanied with the normalized expression levels and enzyme activities of both
      pck1 and g6pca.1. Therefore, Insra and Insrb demonstrate a similar role in
      promoting glycolysis, but Insra is involved in inhibiting gluconeogenesis via
      down-regulating the expression of foxo1a. Our results indicate that Insra and
      Insrb exhibit diversified functions in maintaining glucose homeostasis in
      zebrafish.

PMID- 30102882
TI  - Acute exogenous corticosterone treatments have few effects on courtship and pair
      bonding in zebra finches.
AB  - Stress impacts social relationships. In turn, social relationships buffer the
      stress response in some species. Studies that have investigated the role of
      corticosterone (CORT) on courtship, mate choice, mating, and pairing have found
      mixed results. We therefore tested the role of CORT in these steps of the pairing
      process in the monogamous zebra finch. Male and female zebra finches received
      either one of 2 doses of corticosterone (CORT, 10 MUg and 20 MUg, referred to as
      low and high dose) or a vehicle control (peanut oil). Subjects were then given
      the opportunity to pair in mixed sex aviaries. Courtship and pair bonding
      behaviors were observed over 3 days. Overall, zebra finches of both sexes were
      equally likely to pair or not pair regardless of treatment, although a high dose
      of CORT increased the latency to form a pair bond. There were no effects of CORT
      on courtship behavior in either sex, though the low dose increased undirected
      (non-courtship) singing in males relative to the high dose. Animals treated with
      CORT, regardless of dose, engaged in fewer copulations than did control animals.
      When we examined pairing behaviors, we found a decrease in co-nesting in low dose
      animals. Our results suggest that acute CORT has few effects on pair bonding,
      suggesting species-specific effects of CORT on behavior.

PMID- 30102883
TI  - Cardiac-specific knockout of Lmod2 results in a severe reduction in myofilament
      force production and rapid cardiac failure.
AB  - Leiomodin-2 (Lmod2) is a striated muscle-specific actin binding protein that is
      implicated in assembly of thin filaments. The necessity of Lmod2 in the adult
      mouse and role it plays in the mechanics of contraction are unknown. To answer
      these questions, we generated cardiac-specific conditional Lmod2 knockout mice
      (cKO). These mice die within a week of induction of the knockout with severe left
      ventricular systolic dysfunction and little change in cardiac morphology. Cardiac
      trabeculae isolated from cKO mice have a significant decrease in maximum force
      production and a blunting of myofilament length-dependent activation. Thin
      filaments are non-uniform and substantially reduced in length in cKO hearts,
      affecting the functional overlap of the thick and thin filaments. Remarkably, we
      also found that Lmod2 levels are directly linked to thin filament length and
      cardiac function in vivo, with a low amount (<20%) of Lmod2 necessary to maintain
      cardiac function. Thus, Lmod2 plays an essential role in maintaining proper
      cardiac thin filament length in adult mice, which in turn is necessary for proper
      generation of contractile force. Dysregulation of thin filament length in the
      absence of Lmod2 contributes to heart failure.

PMID- 30102884
TI  - A systems-based model of Alzheimer's disease.
AB  - The new National Institute on Aging and the Alzheimer's Association Research
      Framework for Alzheimer's disease has been developed to accelerate drug discovery
      and offer a common structure and language to construct new Alzheimer's disease
      conceptual models. However, as a "complex" disease, a model based on systems
      level understanding is needed to accommodate the complex, interacting etiologic
      pathways and the system-level changes associated with Alzheimer's disease
      pathogenesis and interventions that are currently known and which will be
      identified in the future. To accomplish this, the evolution of the structure of
      the research framework itself should be encouraged.

PMID- 30102885
TI  - Morphological, genetic and biological characterisation of a novel
      alphabaculovirus isolated from Cryptophlebia peltastica (Lepidoptera:
      Tortricidae).
AB  - Cryptophlebia peltastica is an agricultural pest of litchis and macadamias in
      South Africa with phytosanitary status for certain markets. Current control
      methods rely on chemical, cultural and classical biological control. However, a
      microbial control option has not been developed. An Alphabaculovirus from C.
      peltastica was recovered from a laboratory reared colony and morphologically
      characterised by transmission electron microscopy (TEM). Analysis of occlusion
      bodies indicated a single NPV (SNPV) varying in size from 421 to 1263 nm. PCR
      amplification and sequencing of the polh gene region using universal primers
      followed by BLAST analysis revealed a 93% similarity to a partial polh gene
      sequence from Epinotia granitalis NPV. Further genetic characterisation involving
      single restriction endonuclease (REN) digestion of genomic DNA was carried out to
      generate profiles for comparison against other baculovirus species and potential
      new isolates of the same virus. The complete genome of the virus was sequenced,
      assembled and analysed for a more comprehensive genetic analysis. The genome was
      115728 base pairs (bp) in length with a GC content of 37.2%. A total of 126 open
      reading frames (ORFs) were identified with minimal overlap and no preference in
      orientation. Bioassays were used to determine the virulence of the NPV against C.
      peltastica. The NPV was virulent against C. peltastica with an LC50 value of 6.46
      * 103 OBs/ml and an LC90 value of 2.46 * 105 OBs/ml, and time mortality ranging
      between 76.32 h and 93.49 h. This is the first study to describe the isolation
      and genetic characterisation of a novel SNPV from C. peltastica, which has
      potential for development into a biopesticide for the control of this pest in
      South Africa.

PMID- 30102886
TI  - Effects of Connective Tissue Massage on Pain in Primiparous Women After Cesarean
      Birth.
AB  - OBJECTIVE: To evaluate the efficacy of connective tissue massage to reduce
      postoperative pain in primiparous women on Postoperative Day 1 after unplanned
      cesarean birth. DESIGN: A randomized controlled trial with three groups:
      intervention (Group 1), control or standard care (Group 2), and individualized
      attention (Group 3). SETTING: Family/newborn units of a large teaching hospital
      in the Northeastern United States. PARTICIPANTS: A total of 165 women who
      experienced unplanned cesarean births of singleton newborns at term gestation.
      METHODS: Participants were randomized to three groups: those in Group 1 received
      a 20-minute massage, those in Group 2 received the usual standard of care, and
      those in Group 3 received 20 minutes of individualized attention. On
      Postoperative Day 1, participants completed questionnaires to measure overall
      pain, stress, and relaxation at Time 1 and again 60 minutes later. Daily numeric
      pain ratings and medication consumption data were retrieved from the electronic
      health care records. Latent growth modeling and analysis of variance were used to
      analyze data, as appropriate. RESULTS: Participants in Group 1 had increased
      relaxation (p < .001), decreased pain (p < .001), decreased stress (p < .001),
      and decreased opioid use on Day 1 (p = .031) and Day 2 (p = .006) of the hospital
      stay after the intervention compared with the other groups. Additionally, opioid
      use in Group 1 decreased linearly, whereas the control groups had a nonlinear
      pattern of change. CONCLUSION: Using massage therapy during postoperative
      hospitalization improved relaxation and decreased pain, stress, and opioid use in
      this sample of women after unplanned cesarean births.

PMID- 30102887
TI  - Consequences of culturally-driven ecological specialization: Killer whales and
      beyond.
AB  - Culturally-transmitted ecological specialization occurs in killer whales, as well
      as other species. We hypothesize that some of the remarkable demographic and
      ecological attributes of killer whales result from this process. We formalize and
      model (using agent-based stochastic models parametrized using killer whale life
      history) the cultural evolution of specialization by social groups, in which a
      narrowing of niche breadth is spread and maintained in a group through social
      learning. We compare the demographic and ecological results of cultural
      specialization to those of a similar model of specialization through natural
      selection. We found that specialization, through either the cultural or natural
      selection routes, is adaptive in the short term with specialization often
      increasing fitness. Generalization, in contrast, is rarely adaptive. The cultural
      evolution of specialization can lead to increased rates of group extirpation.
      Specialization has little effect on group size but tends to reduce population
      size and resource abundance. While the two specialization processes produce
      similar results, cultural specialization can be very much faster. The results are
      generally consistent with what we know of the formation and maintenance of
      specialist ecotypes in killer whales, and have implications for the persistence,
      nature and ecological effects of these apex predators.

PMID- 30102888
TI  - Enzymatic reaction sites on a plane formed with four exon-junctions.
AB  - Understanding the interaction of an enzyme with its substrate is important for
      the research of protein function. However, there is still no satisfactory
      explanation for protein folding, in spite of the continuous efforts by many
      excellent researchers. We present a novel approach for analysing enzyme-substrate
      complexes. Previously, we showed how four exon-junctions, in a domain of enzyme
      and carrier protein structures, form a plane around their respective ligands.
      Here, we report the formation of two planes by two combinations of four exon
      junctions within the large enzyme, aspartate aminotransferase. Almost all the
      ligand atoms are located within one plane, while the other plane contains most
      linker-residue atoms of the coenzyme, suggesting that the former and latter
      planes serve as the enzyme reaction and support areas, respectively. Simulation
      results revealed that two-plane formation is possible in the enzyme with four
      random positions; however, the relationship between the coenzyme ligating
      substrate and the plane is significant and is biologically important. We describe
      the formation of such planes around the ligand, including the ligating residue
      for the coenzyme with no substrate.

PMID- 30102889
TI  - Modeling bat prey capture in echolocating bats: The feasibility of reactive
      pursuit.
AB  - Echolocating bats are the only mammals engaging in airborne pursuit. In this
      paper, we implement a reactive model of sonar based prey pursuit in bats. Our
      simulations include a realistic prey localization mechanism as well as a model of
      the bat's motor behavior. In contrast to previous work, our model incorporates
      bats' ability to execute rapid saccadic scanning motions keeping the prey within
      its field of view. Decoupling the flight direction from the gaze direction allows
      our model to capture erratically moving prey using reactive control. We conclude
      that the rapid shifts in gaze direction allow bats to deal with the narrow field
      of view provided by their sonar system.

PMID- 30102890
TI  - Influence of the periprostatic adipose tissue in obesity-associated mouse
      urethral dysfunction and oxidative stress: Effect of resveratrol treatment.
AB  - Obese mice display overactive bladder (OAB) associated with impaired urethra
      smooth muscle (USM) function. In this study, we evaluated the role of the adipose
      tissue surrounding the urethra and prostate in obese mice (here referred as
      periprostatic adipose tissue; PPAT) to the USM dysfunction. Male C57BL6/JUnib
      mice fed with either a standard-chow or high-fat diet to induce obesity were
      used. In PPAT, histological analysis, and qPCR analysis for gp91phox, tumor
      necrosis factor-alpha (TNF-alpha) and superoxide dismutase (SOD) were conducted.
      In USM, concentration-response curves to contractile and relaxing agents, as well
      as measurements of reactive-oxygen species and nitric oxide (NO) levels were
      performed. The higher PPAT area in obese mice was accompanied by augmented
      gp91phox (NOX2) and TNF-alpha expressions, together with decreased SOD1
      expression. In USM of obese group, the contractile responses to phenylephrine and
      vasopressin were increased, whereas the relaxations induced with glyceryl
      trinitrate were reduced. The reactive-oxygen species and NO levels in USM of
      obese mice were increased and decreased, respectively. A higher SOD expression
      was also detected in obese group whilst no changes in the gp91phox levels were
      observed. We next evaluated the effects of the antioxidant resveratrol (100
      mg/kg/day, two-weeks, PO) in the functional alterations and NO levels of obese
      mice. Resveratrol treatment in obese mice reversed both the functional USM
      dysfunction and the reduced NO production. Our data show that PPAT exerts a local
      inflammatory response and increases oxidative stress that lead to urethral
      dysfunction. Resveratrol could be an auxiliary option to prevent obesity
      associated urethral dysfunction.

PMID- 30102891
TI  - Voltammetric determination of aluminum(III) as Al-Alizarin S complex in tea
      leaves and infusions.
AB  - This work presents, for the first time, DPV methodology of indirect aluminum
      (III) determination in tea leaves and infusions using the renewable silver
      amalgam electrode. A self-referencing strategy was proposed which relies on
      alternate voltammetric curves registration with and without conditioning of the
      electrode surface. The developed procedure utilizing formation of aluminum
      Alizarin S complex shows linearity in the range of 2-50 MUg L-1 of Al(III)
      concentration, with r > 0.997. In the case of the electrode conditioning LOD is
      0.2 MUgL-1 and repeatability expressed by CV is 1-2%. Introducing an additional
      operation i.e. electrode activation results in decrease of sensitivity from
      0.0162 to 0.0043 MUA/MUgL-1. The method was verified using CRM (tea leaves). Due
      to the wide variety of tea origin, types and producers, four most popular sorts
      (black, green, red and white) were chosen, made by one manufacturer. It was
      demonstrated that the proposed methodology may be applied in Al(III)
      determination in tea leaves and infusions. Al(III) extraction effectiveness was
      also examined. It was verified, that lemon juice addition during brewing
      increases aluminum concentration in infusions. Using Principal Components
      Analysis it was demonstrated that automatic distinction of infusions brewed with
      and without lemon juice, based on unprocessed voltammetric signal, may be
      successfully realized.

PMID- 30102892
TI  - Distinctive temporal profiles of detergent-soluble and -insoluble tau and Abeta
      species in human Alzheimer's disease.
AB  - Alzheimer's disease (AD) pathology relevant proteins tau and beta-amyloid (Abeta)
      exist as an array of post-translationally modified and conformationally altered
      species with varying abundance, solubility and toxicity. Insoluble
      neurofibrillary tau tangles and Abeta plaques are end-stage AD hallmarks, yet may
      carry less disease significance compared to soluble species. At present, it is
      unclear how soluble and insoluble tau and Abeta relate to each other as well as
      to disease progression. Here, detergent soluble and insoluble fractions generated
      from post-mortem human temporal lobe samples (Brodmann area 21) were probed for
      tau and Abeta markers in immuno-dot assays. Measures were quantified according to
      diagnosis (AD cf. Non-AD), neuropathological severity, and correlated with
      disease progression (Braak stages). All markers were elevated within AD cases cf.
      non-AD controls (p < 0.05) independent of solubility. However, when considered
      according to neuropathological severity, phospho-tau (detected via CP13 and AT8
      antibodies) was elevated early within the soluble fraction (p < 0.05 intermediate
      cf. low severity) and emerged only later within the insoluble fraction (p < 0.05
      high cf. low severity). In contrast, PHF1 phospho-tau, TOC1 reactive tau
      oligomers and amyloid markers rose within the two fractions simultaneously.
      Independent of solubility, cognitive correlations were observed for tau makers
      and for fibrillary amyloid (OC), however only soluble total Abeta was
      significantly correlated with intellectual impairment. Following the exclusion of
      end-stage cases, only soluble total Abeta remained correlated with cognition. The
      data indicate differential rates of protein aggregation during AD progression and
      confirm the disease relevance of early emerging soluble Abeta species.

PMID- 30102893
TI  - Plasticity of Multi-Protein Complexes.

PMID- 30102895
TI  - Bumetanide attenuates acute lung injury by suppressing macrophage activation.
AB  - Bumetanide is a potent loop diuretic that acts as an inhibitor of sodium
      potassium-chloride cotransporter 2 (NKCC2) and its isoform NKCC1. Although the
      expression of NKCC2 is limited to the kidney, NKCC1 is widely expressed in
      various cells, where it participates in a variety of physiological functions
      including ion transport, alveolar fluid secretion, and cell volume regulation. We
      investigated the role of NKCC1 in modulation of host immunity. Lipopolysaccharide
      (LPS) stimulated the expression and phosphorylation of NKCC1 in RAW264.7 cells in
      vitro and activated these cells to produce inflammatory cytokines. Enlarging the
      cell volume in a low-osmotic microenvironment amplified the LPS-induced
      inflammatory responses and phagocytosis activity of RAW264.7 cells. Pretreatment
      with the NKCC1 inhibitor bumetanide attenuated LPS-induced activation of
      inflammatory cells and cell volume-related function. Mice treated with an
      intratracheal bumetanide spray showed greater resistance to LPS-induced tissue
      inflammation and acute lung injury in vivo. Our studies suggest that NKCC1 plays
      a unique role as an amplifier of LPS-induced macrophage functions and that NKCC1
      might be a novel target for treating sepsis-related acute respiratory distress
      syndrome.

PMID- 30102894
TI  - Central venous catheter-related infections caused by Corynebacterium amycolatum
      and other multiresistant non-diphtherial corynebacteria in paediatric oncology
      patients.
AB  - Bloodstream and venous catheter-related corynebacterial infections in paediatric
      patients with haematological cancer were investigated from January 2003 to
      December 2014 at the Brazilian National Cancer Institute in Rio de Janeiro,
      Brazil. We observed that during cancer treatment, invasive corynebacterial
      infections occurred independent of certain factors, such as age and gender,
      underlying diseases and neutropenia. These infections were ssscaused by
      Corynebacterium amycolatum and other non-diphtherial corynebacteria. All cases
      presented a variable profile of susceptibility to antimicrobial agents, except to
      vancomycin. Targeted antibiotic therapy may contribute to catheters maintenance
      and support quality of treatment. Non-diphtherial corynebacteria must be
      recognized as agents associated with venous access infections. Our data highlight
      the need for the accurate identification of corynebacteria species, as well as
      antimicrobial susceptibility testing.

PMID- 30102896
TI  - Increased serum interleukin-33 concentrations predict worse prognosis of
      aneurysmal subarachnoid hemorrhage.
AB  - BACKGROUND: Interleukin-33 (IL-33) is an inflammatory biomarker. We elucidated
      the relationship between serum IL-33 concentrations, severity and prognosis in
      aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We prospectively recruited
      175 controls and 175 aSAH patients. Serum IL-33 concentrations were gauged using
      an enzyme-linked immunosorbent assay. Clinical and radiological severity was
      assessed by World Federation of Neurological Surgeons (WFNS) scale and modified
      Fisher grading scale respectively. Poor outcome was defined as Glasgow Outcome
      Scale score of 1-3. RESULTS: Serum IL-33 concentrations were significantly higher
      in patients than in controls. IL-33 concentrations were significantly increased
      with increasing WFNS scores, modified Fisher scores and serum C-reactive protein
      concentrations. Serum IL-33 emerged as an independent predictor for 6-month
      mortality and poor outcome. Under receiver operating characteristic curve, the
      prognostic predictive ability of serum IL-33 was equivalent to those of WFNS
      scores and modified Fisher scores. Moreover, serum IL-33 significantly improved
      the prognostic predictive performance of WFNS scores and modified Fisher scores.
      CONCLUSIONS: High serum IL-33 concentrations have close relation to the
      inflammation, severity and poor outcome in aSAH, indicating IL-33 might have the
      potential to be an inflammatory biomarker for assessing severity and reflecting
      prognosis of aSAH.

PMID- 30102897
TI  - Multicenter comparison of imprecision at low concentrations of two regulatory
      approved high-sensitivity cardiac troponin I assays.

PMID- 30102898
TI  - Application of ultrasonography in the diagnosis and treatment of cesarean scar
      pregnancy.
AB  - The morbidity of cesarean scar pregnancy (CSP) has shown an obvious ascending
      tendency with the increase of cesarean delivery in China and other countries. The
      timely diagnosis and treatment of CSP currently relies on medical imaging
      technology. In this article, we analyzed and compare the imaging methods in
      diagnosis of CSP. The imaging methods to diagnose CSP include traditional two
      dimensional color/power Doppler ultrasound (2D-US), three-dimensional color/power
      Doppler ultrasound (3D-US), contrast-enhanced ultrasound (CEUS), and Magnetic
      Resonance Imaging (MRI). 2D-US provides important information including the
      location and size of gestational sac (GS), embryo with or without heart activity,
      and the relationship between the GS and scar. It can also divide CSP into
      different types, which are convenient for the choice of clinical treatment. CEUS
      can observe the perfusion of CSP in real-time, the arrival time of GS in CSP is
      earlier than that of the myometrium. It provides reliable evidence for diagnosis
      and evaluation of the treatment of CSP, which is helpful for making treatment
      plans and post-treatment follow-up. Combined use of ultrasound and CEUS could be
      a problem-solving method for CSP when conventional ultrasound is often
      inconclusive. Ultrasound has been accepted as the first-line imaging method and
      an important guiding method for CSP, supervising local methotrexate injection and
      curettage.

PMID- 30102899
TI  - Are Seating Systems With a Medial Knee Support Really Helpful for Hip
      Displacement in Children With Spastic Cerebral Palsy GMFCS IV and V?
AB  - OBJECTIVE: To evaluate whether medial knee support (MKS) in seating systems
      aggravates hip displacement in children with cerebral palsy (CP). DESIGN:
      Retrospective chart review. SETTING: Rehabilitation department of tertiary
      university hospital. PARTICIPANTS: Children with CP (N=76) using seating systems
      (intervention group, n=42; mean age 6.86y) and using regular wheelchairs (control
      group, n=34; mean age 8.15y). INTERVENTIONS: The intervention group was provided
      with a seating system with MKS. We enrolled children who did not use a seating
      system in the control group, retrospectively. MAIN OUTCOME MEASURES: By
      radiographic images, Reimer's migration index (MI), lateral center edge angle
      (CEA), and femur neck shaft angle (NSA) were measured. We compared the
      demographic data, clinical variables, and radiographs between the 2 groups.
      RESULTS: In the intervention group, there was a significant deterioration in the
      MI, from 26.89% to 44.18% after using the system (P<.001). The progression of MI
      was 14.72% and 7.82% per year in the intervention and control groups,
      respectively (P=.016). CONCLUSION: We should consider the possibility that
      seating systems with MKS may exacerbate hip displacement in children with CP.

PMID- 30102900
TI  - Opioid Prescription Patterns for Adults With Longstanding Disability and
      Inflammatory Conditions Compared to Other Users, Using a Nationally
      Representative Sample.
AB  - OBJECTIVES: To investigate the opioid prescription patterns for adults with
      longstanding physical disability and inflammatory conditions, compared to a mixed
      group of other opioid users, after excluding cancer patients. DESIGN: Nationally
      representative cross-sectional study, 2010-2014. SETTING: Medical Expenditure
      Panel Survey (MEPS). PARTICIPANTS: The participants (N=7134) were adults who
      participated in MEPS and had at least 1 opioid prescription, did not have cancer,
      and were between 18 years and 64 years of age. The participants were grouped as
      longstanding physical disability (group 1), inflammatory conditions (group 2),
      and a mixed group with at least 1 opioid prescription during the 2-year study
      period (comparison group). Participants with both groups of conditions were
      excluded. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Morphine milligram
      equivalent (MME) doses for each participant were cumulated over a 2-year panel
      period. RESULTS: By using quantile regression, cumulative MME in groups 1 and 2
      was higher than the comparison group across all the percentiles, and differences
      between condition groups and comparison group became larger in higher
      percentiles. Participants in group 1 had the highest cumulative MME in 75th and
      90th percentiles after controlling for other covariates. CONCLUSIONS: This study
      documented the opioid prescription patterns for patients with longstanding
      physical disability or inflammatory conditions. All indexed groups (groups 1 and
      2) had higher MME use compared to the comparison group.

PMID- 30102901
TI  - Urban-Rural Differences in Service Utilization and Costs of Care for Racial
      Ethnic Groups Hospitalized With Poststroke Aphasia.
AB  - OBJECTIVE: Although residence is a key contributor to cost and utilization in
      stroke patient care, its contribution to the care of persons with aphasia (PWA)
      is unknown. The objective of this study was to use discharge-level hospital
      inpatient data to examine the influence of patient residence (rural vs urban) and
      race-ethnicity on service utilization and cost of care among PWA. DESIGN: Cross
      sectional. SETTING: Administrative data from acute care hospitals in the state of
      North Carolina. PARTICIPANTS: Individuals (N=4381) with poststroke aphasia.
      INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Length of stay (LOS), speech-language
      pathology (SLP) service utilization, costs of care. METHODS: The 2011-2012
      Healthcare Cost and Utilization Project State Inpatient Database data were
      analyzed to examine the effect of rural or urban residence on LOS, SLP service
      utilization, as well as total inpatient and SLP service costs. These outcomes
      were further analyzed across both residence and racial groups (non-Hispanic white
      and non-Hispanic black). Outcomes were analyzed using generalized linear model.
      RESULTS: Both rural and urban black PWA experienced longer average LOS after
      controlling for demographics, illness severity, and the hospital where they
      received care. Rural blacks experienced longer LOS, received greater SLP
      services, and incurred greater average total hospital costs than their rural
      white counterparts after adjusting for differences in their demographics and
      stroke or illness severity. The differences were attenuated after controlling for
      the hospital where they received care. CONCLUSIONS: For PWA, race-ethnicity has a
      larger effect on average total medical costs, SLP service utilization, and LOS
      than residence. It is unclear how and why blacks with aphasia have greater
      service utilization and costs in acute care, yet their aphasia outcomes are
      worse. Future studies are required to explore potential factors such as quality
      of care.

PMID- 30102902
TI  - Dickkopf-1: Current knowledge and related diseases.
AB  - Dickkopf-1(DKK-1) has been identified as a secretory protein that can inhibit the
      Wnt signaling transduction pathway. It is well known that the Wnt signaling
      pathway plays an important role in embryogenesis, organogenesis and homeostasis.
      This signaling cascade is essential for many normal physiological processes such
      as cellular proliferation, tissue regeneration, embryonic development and many
      other systemic and local effects, and it can be regulated at different levels.
      Therefore, defects in the pathway may lead to some complicated effects. In
      addition, it has been demonstrated that defects in this pathway are closely
      linked to some diseases including cancer, rheumatism, bone disease, diabetes, and
      Alzheimer disease. Since DKK-1 is an antagonist of the Wnt pathway, it may be
      related to these diseases; in fact, many studies have identified this fact. This
      review will summarize the current knowledge of DKK-1 and DKK-1-mediated
      regulation of Wnt signaling in the development of these related diseases.

PMID- 30102903
TI  - Soluble MHC class I complexes for targeted immunotherapy.
AB  - Major histocompatibility complexes (MHC) have been used for more than two decades
      in clinical and pre-clinical approaches of tumor immunotherapy. They have been
      proven efficient for detecting anti-tumor-specific T cells when utilized as
      soluble multimers, immobilized on cells or artificial structures such as
      artificial antigen-presenting cells (aAPC) and have been shown to generate
      effective anti-tumor responses. In this review we summarize the use of soluble
      MHC class I complexes in tumor vaccination studies, highlighting the different
      strategies and their contradicting results. In summary, we believe that soluble
      MHC class I molecules represent an exciting tool with great potential to impact
      the understanding and development of immunotherapeutic approaches on many levels
      from monitoring to treatment.

PMID- 30102904
TI  - Resorcinolic lipid 3-heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one is a strategy
      for melanoma treatment.
AB  - AIMS: Previous studies performed by our research group indicated that cytosporone
      analogues are capable of prevent or repair DNA damages. This work presents the
      evaluation of the activity of AMS35AA for metastatic murine melanoma cells
      (B16F10) in experimental model in vitro and, in pre-clinic assay of metastatic
      melanoma in vivo, using mice lineage C57BL/6. MAIN METHODS: In vitro assays were
      performed: MTT and comet assay, flow cytometry evaluation, gene expression assay
      by RT-PCR, qualitative evaluation of cell death using B16F10 cells. In vivo
      assays: micronucleus and comet assay, splenic phagocytosis, melanoma murine model
      and histopathological analysis, using mice lineage C57BL/6 (n = 20). KEY
      FINDINGS: In vitro results performed by MTT assay showed that AMS35AA is
      cytotoxic for B16F10 cells (p < 0.05). Based on comet assay the genotoxicity of
      the IC50 was determined (95.83 MUg/mL) (p < 0.05). These data were corroborated
      by flow cytometry analysis after the treatment with AMS35AA, which indicates the
      cellular death by apoptosis (p < 0.05) and increasing of ATR, p53, p21 and GADD45
      gene expressions verified using RT-PCR. With respect to in vivo results, it was
      observed that AMS35AA did not show genotoxic activity. Data of tumor volume ex
      vivo indicate reduction of tumor for the treated animals with AMS35AA up to
      15.84*, which is superior to Dacarbazina (50 mg/Kg, p.c.; i.p.). SIGNIFICANCE: In
      summary, the study showed that AMS35AA reveals relevant results regarding to
      cytotoxicity of B16F10 murine melanoma cells, inducing death by apoptosis via
      mitochondrial and/or mediated by DNA damages.

PMID- 30102905
TI  - Can you guess the colour of this moving object? A dissociation between colour and
      motion in blindsight.
AB  - Blindsight has been primarily and extensively studied by Lawrence Weiskrantz.
      Residual visual abilities following a hemispheric lesion leading to homonymous
      hemianopia encompass a variety of visual-perceptual and visuo-motor functions.
      Attention blindsight produces the more salient subjective experiences, especially
      for motion (Riddoch phenomenon). Action blindsight illustrates visuo-motor
      abilities despite the patients' feeling that they produce random movements.
      Perception blindsight seems to be the weakest residual function observed in
      blindsight, e.g. for wavelength sensitivity. Discriminating motion produced by
      isoluminant colours does not give rise to blindsight for motion but the outcome
      of the reciprocal test is not known. Here we tested whether moving stimuli could
      give rise to colour discrimination in a patient with homonymous hemianopia. It
      was found that even though the patient exhibited nearly perfect performances for
      motion direction discrimination his colour discrimination for the same moving
      stimulus remained at chance level. It is concluded that easily discriminated
      moving stimuli do not give rise to colour discrimination and implications for the
      3 levels of blindsight taxonomy are discussed.

PMID- 30102906
TI  - Size matters: Grey matter brain reserve predicts executive functioning in the
      elderly.
AB  - Preserved executive functioning (EF) is crucial for daily functioning in the
      elderly and it appears to predict dementia development. We sought to clarify the
      role of atrophy-corrected cortical grey matter (GM) volume as a potential brain
      reserve (BR) marker for EF in the elderly. In total, 206 pre-surgical subjects
      (72.50 +/- 4.95 years; mean MMSE score 28.50) were investigated. EF was primarily
      assessed using the Trail Making Test B (TMT B). Global/ lobar GM volumes were
      acquired with T1 MP-RAGE. Adjusting for key covariates including a brain atrophy
      index (i.e. brain parenchymal fraction), multiple linear regression analysis was
      used to study associations of GM volumes and TMT B. All GM volumes - most notably
      of global GM - were significantly associated with TMT B independently of GM
      atrophy (beta = -0.201 to -0.275, p = 0.001-0.012). Using atrophy-corrected GM
      volume as an estimate of maximal GM size in youth may serve as a BR predictor for
      cognitive decline in future studies investigating BR in the elderly.

PMID- 30102907
TI  - Fast, Broad, and Irregular: Wolff-Parkinson-White Syndrome.

PMID- 30102908
TI  - Contemporary Management and Outcomes of Patients with Massive and Submassive
      Pulmonary Embolism.
AB  - BACKGROUND: Few contemporary studies have assessed the management and outcomes of
      patients with massive and submassive pulmonary embolism. Given advances in
      therapy, we report contemporary practice patterns and event rates among these
      patients. METHODS: We analyzed a prospective database of patients with massive
      and submassive pulmonary embolism. We report clinical characteristics, therapies,
      and outcomes stratified by pulmonary embolism type. Treatment escalation beyond
      systemic anticoagulation was defined as advanced therapy. Cox proportional
      hazards regression was used to identify predictors of 90-day mortality. RESULTS:
      Among 338 patients, 46 (13.6%) presented with massive and 292 (86.4%) with
      submassive pulmonary embolism. The average age was 63 +/- 15 years, 49.9% were
      female, 32.0% had malignancy, and 21.9% had recent surgery. Massive pulmonary
      embolism patients received advanced therapy in 71.7% (30.4% systemic
      thrombolysis, 17.4% catheter-directed thrombolysis, 15.2% surgical embolectomy)
      and had greater 90-day mortality rates compared with submassive pulmonary
      embolism patients (41.3% vs 12.3%, respectively; P < .01). Most massive pulmonary
      embolism deaths (78.9%) occurred in-hospital, whereas mortality risk persisted
      after discharge for submassive pulmonary embolism. After multivariable
      adjustment, massive pulmonary embolism was associated with a 5.23-fold greater
      hazard of mortality (95% confidence interval, 2.70-10.13; P < .01). Advanced
      therapies among all pulmonary embolism patients were associated with a 61%
      reduction in mortality (95% confidence interval, 0.20-0.76; P < .01).
      CONCLUSIONS: Among contemporary massive and submassive pulmonary embolism
      patients, mortality remains substantial. Advanced therapies were frequently
      utilized and independently associated with lower mortality. Further investigation
      is needed to determine how to improve outcomes among these high-risk patients,
      including the optimal use of advanced therapies.

PMID- 30102910
TI  - A Missing Link: Sarcoid-Lymphoma Syndrome.

PMID- 30102911
TI  - A Hoarse Warning: Ortner Syndrome.

PMID- 30102909
TI  - Weight Gain and Health Affliction Among Former National Football League Players.
AB  - BACKGROUND: Professional American-style football players are among the largest
      athletes across contemporary sporting disciplines. Weight gain during football
      participation is common, but the health implications of this early-life weight
      gain remain incompletely understood. We sought to define weight trajectories of
      former professional American-style football athletes and to establish their
      relationship with 5 common health afflictions (cardiovascular disease,
      cardiometabolic disease, neurocognitive impairment, sleep apnea, and chronic
      pain). METHODS: A health survey was distributed to former National Football
      League (NFL) players. Former players reported body weight at 4 time points (high
      school, college, professional, and time of survey response) as well as maximal
      retirement weight. Logistic regression was used to assess associations between
      weight gain during football participation and health affliction. RESULTS: In this
      cohort of former NFL players (n = 3,506, age 53 +/- 14 years), mean weight
      increase from high school to time of survey response was 40 +/- 36 pounds, with
      the majority of weight gain occurring during periods of football participation
      (high-school-to-college and college-to-professional). The prevalence of health
      afflictions ranged from 9% (cardiovascular disease) to 28% (chronic pain). Weight
      gain during football participation was independently associated with risk of
      multiple later-life health afflictions in models adjusted for football exposure,
      lifestyle variables, and post-career weight gain. CONCLUSIONS: Early-life weight
      gain among American-style football athletes is common and is associated with risk
      of adverse health profiles during later-life. These findings establish football
      associated weight gain as a key predictor of post-career health and raise
      important questions about the central role of targeted weight gain in this
      population.

PMID- 30102912
TI  - B Minus: Wernicke's Encephalopathy.

PMID- 30102913
TI  - An Oscillating Thrombus Inside the Inferior Vena Cava.

PMID- 30102914
TI  - Quite a Stretch: Internal Oblique Muscle Hematoma.

PMID- 30102915
TI  - High glucose concentration suppresses a SIRT2 regulated pathway that enhances
      neurite outgrowth in cultured adult sensory neurons.
AB  - In peripheral nerve under hyperglycemic conditions high flux of d-glucose through
      the polyol pathway drives an aberrant redox state contributing to
      neurodegeneration in diabetic sensorimotor polyneuropathy (DSPN). Sirtuins,
      including SIRT2, detect the redox state via the NAD+/NADH ratio to regulate
      mitochondrial function via, in part, AMP-activated protein kinase (AMPK) and
      peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC
      1alpha). In adult dorsal root ganglia (DRG) sensory neurons mitochondrial
      dysfunction has been proposed as an etiological factor in dying-back neuropathy
      in diabetes. We tested the hypothesis that a high concentration of d-glucose
      depleted SIRT2 expression via enhancement of polyol pathway activity. We posited
      that this would lead to impaired mitochondrial function and suppression of
      neurite outgrowth in cultured sensory neurons. The use of dominant negative
      mutants or neurons from SIRT2 knockout (KO) mice to block SIRT2 signaling
      revealed that neurons derived from control or type 1 diabetic rodents required
      SIRT2 for optimal neurite outgrowth. Over-expression of WT-SIRT2 elevated neurite
      outgrowth in normal and diabetic cultures. SIRT2 protein isoforms 2.1 and 2.2
      were reduced by 20-30% in DRG of type 1 diabetic mice (p < .05). After 72 h
      exposure to high d-glucose (25 mM vs 5 mM) cultured sensory neurons showed a
      significant 2-fold (p < .05) decrease in SIRT2 expression, P-AMPK, levels of
      respiratory Complexes II/III and respiratory capacity. DRG neurons expressed
      aldose reductase and the aforementioned deficits were prevented by treatment with
      aldose reductase inhibitors (lidorestat or sorbinil) or sorbitol dehydrogenase
      inhibitor (SDI-158). In cultures derived from type 1 diabetic rats treatment with
      SDI-158 elevated expression of SIRT2, P-AMPK/PGC-1alpha and neurite outgrowth (p
      < .05). SIRT2 KO neurons exhibited deficits in the LKB-1/AMPK/PGC-1alpha pathway
      and mitochondrial function. In cultured neurons the SIRT2 pathway enhances axonal
      outgrowth and this signaling axis encompassing activation of AMPK/PGC-1alpha is
      impaired in DSPN, in part, due to enhanced polyol pathway activity caused by
      hyperglycemia.

PMID- 30102916
TI  - Targeting histone deacetylation for recovery of maternal deprivation-induced
      changes in BDNF and AKAP150 expression in the VTA.
AB  - Severe early life stressors increase the probability of developing psychiatric
      disorders later in life through modifications in neuronal circuits controlling
      brain monoaminergic signaling. Our previous work demonstrated that 24 h maternal
      deprivation (MD) in male Sprague Dawley rats modifies dopamine (DA) signaling
      from the ventral tegmental area (VTA) through changes at GABAergic synapses that
      were reversible by in vitro histone deacetylase (HDAC) inhibition which led to
      restoration of the scaffold A-kinase anchoring protein (AKAP150) signaling and
      subsequently recovered GABAergic plasticity (Authement et al., 2015). Using a
      combination of in situ hybridization, Western blots and immunohistochemistry, we
      confirmed that MD-induced epigenetic modifications at the level of histone
      acetylation were associated with an upregulation of HDAC2. MD also increased
      Akap5 mRNA levels in the VTA. Western blot analysis of AKAP150 protein expression
      showed an increase in synaptic levels of AKAP150 protein in the VTA with an
      accompanying decrease in synaptic levels of protein kinase A (PKA). Moreover, the
      abundance of mature brain-derived neurotrophic factor (BDNF) protein of VTA
      tissues from MD rats was significantly lower than in control groups. In vivo
      systemic injection with a selective class I HDAC inhibitor (CI-994) was
      sufficient to reverse MD-induced histone hypoacetylation in the VTA for 24 h
      after the injection. Furthermore, HDAC inhibition normalized the levels of mBDNF
      and AKAP150 proteins at 24 h. Our data suggest that HDAC-mediated targeting of
      BDNF and AKAP-dependent local signaling within VTA could provide novel
      therapeutics for prevention of later-life psychopathology.

PMID- 30102917
TI  - Chloride ions stabilize the glutamate-induced active state of the metabotropic
      glutamate receptor 3.
AB  - Due to the essential roles of glutamate, detection and response to a large range
      of extracellular concentrations of this excitatory amino acid are necessary for
      the fine-tuning of brain functions. Metabotropic glutamate receptors (mGluRs) are
      implicated in shaping the activity of many synapses in the central nervous
      system. Among the eight mGluR subtypes, there is increasing interest in studying
      the mGlu3 receptor which has recently been linked to various diseases, including
      psychiatric disorders. This receptor displays striking functional properties,
      with a high and, often, full basal activity, making its study elusive in
      heterologous systems. Here, we demonstrate that Cl- ions exert strong positive
      allosteric modulation of glutamate on the mGlu3 receptor. We have also identified
      the molecular and structural determinants lying behind this allostery: a unique
      interactive "chloride-lock" network. Indeed, Cl- ions dramatically stabilize the
      glutamate-induced active state of the extracellular domain of the mGlu3 receptor.
      Thus, the mGlu3 receptors' large basal activity does not correspond to a
      constitutive activity in absence of agonist. Instead, it results mostly from a Cl
      mediated amplified response to low ambient glutamate concentrations, such as
      those measured in cell media. This strong interaction between glutamate and Cl-
      ions allows the mGlu3 receptor to sense and efficiently react to sub-micromolar
      concentrations of glutamate, making it the most sensitive member of mGluR family.

PMID- 30102918
TI  - Serum noncholesterol sterols in Alzheimer's disease: the Helsinki Businessmen
      Study.
AB  - Cerebral cholesterol metabolism is perturbed in late-onset Alzheimer's disease
      (AD), but whether also the extracerebral cholesterol metabolism is perturbed is
      not known. Thus, we studied whole-body cholesterol synthesis and absorption with
      serum noncholesterol sterols in men without AD (n = 114) or with (n = 18) "pure"
      AD (no concomitant atherosclerotic cardiovascular disease) in a long-term cohort
      (the Helsinki Businessmen Study) of home-dwelling older men without lipid
      lowering drugs and on their habitual home diet. Serum lipids did not differ
      between AD and controls, but age was higher (78 +/- 1 vs 74 +/- 0.3 years, mean
      +/- standard error, P < 0.001), age-adjusted plasma glucose concentration was
      lower (4.8 +/- 0.3 vs 5.7 +/- 0.1 mmol/L, P = 0.011), and APOE epsilon4 allele
      and frailty were more frequent in AD than in controls. Of the age and frailty
      adjusted serum noncholesterol sterols desmosterol and lathosterol ratios to
      cholesterol reflecting cholesterol synthesis were lower in AD than in controls
      (eg, lathosterol 114 +/- 12 vs 137 +/- 5 102 umol/mmol cholesterol, P = 0.004).
      Cholestanol ratio to cholesterol was higher in AD than in controls suggesting
      increased cholesterol absorption. lathosterol/sitosteroll ratio reflecting
      cholesterol metabolism was lower in AD than in controls (0.95 +/- 0.28 vs 1.52 +/
      0.11 102 umol/mmol cholesterol, P = 0.027). In AD, plasma glucose correlated
      negatively with cholesterol synthesis, whereas in controls the correlation was
      positive. In conclusion, extracerebral cholesterol metabolism was altered in AD.
      This finding along with the low plasma glucose concentration and its paradoxical
      interaction with cholesterol synthesis opens new perspectives in the regulation
      of cholesterol metabolism and glucose homeostasis in AD.

PMID- 30102919
TI  - The analysis of underivatized beta-Methylamino-L-alanine (BMAA), BAMA, AEG & 2,4
      DAB in Pteropus mariannus mariannus specimens using HILIC-LC-MS/MS.
AB  - beta-Methylamino-L-alanine (BMAA) has been identified as the potential cause of
      the amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC)
      observed in the Chamorro people of Guam. The principal hypothesis for BMAA
      exposure and intoxication relies on the biomagnification of BMAA in flying fox
      specimens ingested by the Chamorro people. Although high levels of BMAA were
      quantitated in flying fox specimens utilizing liquid chromatography-fluorescence
      (LC-FL), there have not been any confirmatory analyses conducted to date.
      Therefore, a method for the tissue homogenization, extraction and direct analysis
      of BMAA (including BAMA, 2,4-DAB and AEG) was utilized. The approach was applied
      to mammalian dried skin and hair from various rodent species (negative controls)
      and archived flying fox (Pteropus mariannus mariannus) specimens. A positive
      control sample of homogenized mussel (Mytelius edulis) with native BMAA was used
      to verify the method. It was determined that the direct analysis using HILIC
      MS/MS required additional quality control in order to allow for the confident
      identification of BMAA due to the near co-elution of BAMA. BMAA was not present
      above 0.2 MUg g-1 (free fraction) or 2.8 MUg g-1 (total fraction) in the flying
      fox specimens. While analysis did not result in BMAA detection in flying fox or
      negative control samples, the positive control sample and spiked samples were
      successfully detected.

PMID- 30102920
TI  - Multiple, Synchronous Lesions of Differing Histology Within the Same Testis:
      Ultrasonographic and Pathologic Correlations.
AB  - OBJECTIVE: To describe ultrasound (US) and pathologic findings in 11 patients
      with multiple, synchronous lesions of different histology within the same testis.
      MATERIALS AND METHODS: We reviewed US and pathologic findings in 11 patients with
      multiple, synchronous lesions of different histology within the same testis.
      Lesions were classified as separate or adjacent one to another and attempt was
      made to predict tumor type on their US textures. Pathologic review assessed
      presence of normal tissue between adjacent lesions and of Germ Cell Neoplasia In
      Situ in surrounding parenchyma. Nine cases were from files specifically dedicated
      to testicular tumors and estimated prevalence was calculated. RESULTS: Two
      nodules were seen in nine patients and 3 in remaining two. Nine had tumors of
      different histology; two had one malignancy and one focal benign lesion. Germ
      Cell Neoplasia In Situ was seen in 7/11 cases. In dedicated archives, these
      lesions had 1.83% prevalence. CONCLUSION: Multiple focal lesions identified at
      imaging within the testis are not always of the same histology. This can be
      suspected in some cases basing on US texture. Recognition that lesions are
      multiple and an indication of their locations within the testis is the most
      important role of imaging and may help pathologists correctly sample the specimen
      to establish nature of each of them. Presence of multiple lesions is regarded as
      a contraindication to testicular sparing surgery. In two of our patients, one
      lesion was benign. Then, when the procedure is indicated all lesions have to be
      sampled and assessed by pathologists before deciding between conservative or
      radical technique.

PMID- 30102921
TI  - Family Planning and Pregnancy Management in Adults with Congenital Heart Disease.
AB  - With advances in congenital heart disease management, there are an increasing
      number of women reaching reproductive age. Pregnancy results in a surge of
      hormones and increased demands on both the cardiovascular (CV) and respiratory
      systems. Depending on the heart defect and the treatments the mother has
      undergone, these hemodynamic changes can result in an increased risk of maternal
      CV events and an increased risk of fetal morbidity and mortality. Thus, it is
      important to have a comprehensive approach to adult congenital heart disease
      patients involving pre-pregnancy planning in addition to diligent peri- and post
      partum care.

PMID- 30102922
TI  - Bilingualism shapes the other race effect.
AB  - It has recently been suggested that the other race effect (ORE), whereby own race
      faces are recognised better than those of other races, can be abolished by
      bilingualism.Bilingualism, however, is not a categorical variable but can vary
      dramatically in proficiency across the two languages. We therefore hypothesised
      that increasing bilingual proficiency should be associated with a diminishing
      ORE. To test this, we asked a group of bilingual Singaporean Chinese individuals
      to complete the Asian and Caucasian Cambridge Face Memory Tests. In contrast to
      recent work, our bilinguals did as a group exhibit an ORE, however, the magnitude
      of this effect decreased as reported cross-language proficiency increased;
      Chinese, rather than English, listening ability drove this association. This
      relationship persisted even when taking into account our participants' exposure
      to Caucasians, own race memory ability, age, and gender. Moreover, we discounted
      the possibility that bilingualism merely reflected participants' underlying
      intelligence. Increasing auditory bilingualism thus diminishes perceptual
      narrowing for faces. We propose that other race recognition ability reflects the
      base level of intrinsic, domain specific face memory, whereas the distance in
      recognition performance between own and other race faces is comprised of a domain
      general process related to stimulus individuation. Finally, our results have
      serious implications for how we can interpret prior research investigating the
      ORE, and culture's influence on visual perception, due to the confounding
      influence of bilingualism.

PMID- 30102923
TI  - Fast random motion biases judgments of visible and occluded motion speed.
AB  - Human sensitivity to speed differences is very high, and relatively high when one
      has to compare the speed of an object that disappears behind an occluder with a
      standard. Nevertheless, different speed illusions (by contrast, adaptation,
      dynamic visual noise) affect proper speed judgment for both visible and occluded
      moving objects. In the present study, we asked whether an illusion due to non
      directional motion noise (random dynamic visual noise, rDVN) intervenes at the
      level of speed encoding, thus affecting speed discrimination, or at the level of
      speed decoding by non-sensory decision-making mechanisms, indexed by speed
      overestimation of visible and invisible motion. In Experiment 1, participants
      performing a temporal two-Alternative Forced Choice task, judged the speed of a
      target moving in front of the rDVN or a static visual noise (SVN). In Experiment
      2 and 3, the target disappeared behind the rDVN/SVN, and participants reported
      whether the target reappeared early or late (Experiment 2), or the time to
      contact (TTC) with the end of the occluded trajectory (Experiment 3). In
      Experiment 1 and 2, we found that rDVN affected the point of subjective equality
      (pse) of the individual's psychometric function in a way indicating speed
      overestimation, while not affecting speed discrimination threshold (just
      noticeable differences, jnd). In Experiment 3 the rDVN reduced the TTC. Though
      not entirely consistent, our results suggest that a similar speed decoding
      mechanism, which read-out motion information to form a perceptual decision,
      operates regarding of whether motion is visible or invisible.

PMID- 30102924
TI  - A novel multiplex PCR-electronic microarray assay for rapid and simultaneous
      detection of bovine respiratory and enteric pathogens.
AB  - Respiratory and enteric diseases continue to be two major causes of economic
      losses to the cattle industry worldwide. Despite their multifactorial etiology,
      the currently available diagnostic tests for bovine respiratory disease complex
      (BRDC) and bovine enteric disease (BED) are single-pathogen-tests. DNA microarray
      when combined with multiplex polymerase chain reaction (PCR) is a powerful tool
      in detection and differentiation of multiple pathogens in a single sample. This
      study reports development and initial validation of two independent highly
      sensitive and specific multiplex PCR-electronic microarray assays, one for the
      detection and differentiation of pathogens of the BRDC and the other for
      detection and differentiation of pathogens of the BED. The BRDC multiplex PCR
      microarray assay was able to detect and differentiate four bacteria (Mannheimia
      haemolytica, Histophilus somni, Pasteurella multocida, and Mycoplasma bovis) and
      five viruses [bovine parainfluenza virus-3, bovine respiratory syncytial virus,
      bovine herpesvirus-1, bovine coronavirus (BCoV), and bovine viral diarrhea virus
      (BVDV)] associated with BRDC. The BED multiplex PCR- microarray- assay was able
      to detect and differentiate four bacteria (Clostridium perfringens, Escherichia
      coli, Salmonella enterica Dublin, and Salmonella enterica Typhimurium), three
      protozoa (Eimeria zuernii, Eimeria bovis, and Cryptosporidium parvum), and four
      viruses (bovine torovirus, bovine rotavirus, BCoV, and BVDV) associated with the
      BED. Both assays detected their respective targets individually or in combination
      when present. The limit-of-detection of each assay at the PCR amplification and
      DNA microarray levels was determined using previously titrated laboratory
      amplified target pathogens or using quantified synthetic nucleotides. Both assays
      showed very high analytical sensitivity and specificity, and were validated using
      a limited number of clinical samples. The BRDC and BED multiplex PCR- microarray
      assays developed in this study, with further clinical validation, could be used
      in veterinary diagnostic laboratories for the rapid and simultaneous
      identification of pathogens to facilitate quick and accurate decision making for
      the control and treatment of these two economically important disease complexes.
      Furthermore, these assays could be very effective tools in epidemiological
      studies as well as for screening of healthy animals to identify carriers that may
      potentially develop BRDC or BED.

PMID- 30102925
TI  - Emotional stress regulation: The role of relative frontal alpha asymmetry in
      shaping the stress response.
AB  - Frontal EEG asymmetry has been proposed as an index of emotional regulation,
      reflecting both state and trait components, and there is evidence that these
      factors influence the cortisol response to stress. Here, we asked whether cold
      pressor stress modulates frontal asymmetry and whether this is predictive of the
      neuroendocrine stress response. Twenty-four male participants underwent an
      automatized bilateral feet cold pressor test (bfCPT) and a warm water control
      procedure in counterbalanced order on two separate days, one week apart. EEG,
      heart rate and blood pressure were assessed at baseline as well as during and
      after the bfCPT. Salivary cortisol and subjective ratings of stress and arousal
      were assessed before and after the bfCPT. The bfCPT led to a significant increase
      in cortisol, cardiovascular parameters and in subjective ratings of stress and
      arousal that was absent in the control condition. Furthermore, analysis of
      relative frontal alpha-band asymmetry revealed a stronger relative right frontal
      activation during the bfCPT compared to the control condition at electrode pairs
      F7/8 but not F3/4. However, frontal asymmetry scores during the bfCPT were not
      predictive for neither physiological responses nor subjective ratings. Moreover,
      an association between physiological responses and frontal asymmetry assessed
      during rest at baseline could be observed at electrode pairs F3/F4, with stronger
      responses being associated with stronger relative right frontal activation. Our
      results show that cold pressor stress leads to an alteration of emotional
      processes as reflected in frontal EEG asymmetry at F7/F8. Moreover, physiological
      responses to the CPT seem to be differentially moderated by trait and state
      components present in frontal asymmetry.

PMID- 30102926
TI  - Proteomic analysis of 2-monochloropropanediol (2-MCPD) and 2-MCPD dipalmitate
      toxicity in rat kidney and liver in a 28-days study.
AB  - 2-monochloropropanediol (2-MCPD), 3-monochloropropanediol (3-MCPD) and their
      fatty acid esters have recently been identified as heat-induced contaminants in
      fat- and salt-containing foodstuff. Toxicity of 3-MCPD has been studied
      previously in some detail. Disturbance of glycolysis and cellular redox functions
      appear to be involved in 3-MCPD toxicity. By contrast, only very few
      toxicological data are available for 2-MCPD or 2-MCPD esters, especially at the
      molecular level. This study was therefore aimed to provide a comprehensive
      overview of proteomic alterations induced in rat kidney and liver by 2-MCPD and 2
      MCPD dipalmitate, a representative 2-MCPD fatty acid ester. Sub-toxic doses of 10
      mg/kg body weight 2-MCPD, or equimolar doses of 2-MCPD dipalmitate were applied
      in a 28-day in vivo gavage oral toxicity study in male rats. Two-dimensional gel
      electrophoresis and mass-spectrometric protein identification using material from
      5 animals per treatment group were employed together with bioinformatic data
      mining to obtain information about the molecular basis of the observed proteomic
      alterations. Obtained data indicate toxic consequences of 2-MCPD exposure in the
      kidney and provide evidence that 2-MCPD exerts its cellular effects in rat kidney
      by mechanisms different from 3-MCPD.

PMID- 30102927
TI  - Comment on "Do flavouring compounds contribute to aldehyde emissions in e
      cigarettes?" by Farsalinos and Voudris.
AB  - This letter is in response to a paper "Do flavouring compounds contribute to
      aldehyde emissions in e-cigarettes?" authored by Farsalinos and Voudris in the
      May 2018 edition of FCT. Our purpose is to point out and/or correct
      inconsistencies and inaccuracies in that paper. Using evidence from several
      independent studies, we demonstrate that experimental methods used by Farsalinos
      and Voudris do not fully account for neither particle nor gas-phase aldehydes in
      e-cigarette aerosols, leading to significant underestimation of aldehyde
      emissions and risks associated with e-cigarette use.

PMID- 30102928
TI  - Reply.

PMID- 30102929
TI  - MicroRNA in lung cancer: role, mechanisms, pathways and therapeutic relevance.
AB  - Lung cancer is the cardinal cause of cancer-related deaths with restricted
      recourse of therapy throughout the world. Clinical success of therapies is not
      very promising due to - late diagnosis, limited therapeutic tools, relapse and
      the development of drug resistance. Recently, small ~20-24 nucleotides molecules
      called microRNAs (miRNAs) have come into the limelight as they play outstanding
      role in the process of tumorigenesis by regulating cell cycle, metastasis,
      angiogenesis, metabolism and apoptosis. miRNAs essentially regulate gene
      expression via post-transcriptional regulation of mRNA. Nevertheless, few studies
      have conceded the role of miRNAs in activation of gene expression. A large body
      of data generated by numerous studies is suggestive of their tumor-suppressing,
      oncogenic, diagnostic and prognostic biomarker roles in lung cancer. They have
      also been implicated in regulating cancer cell metabolism and resistance or
      sensitivity towards chemotherapy and radiotherapy. Further, miRNAs have also been
      convoluted in regulation of immune checkpoints - Programmed death 1 (PD-1) and
      its ligand (PD-L1). These molecules play a significant role in tumor immune
      escape leading to the generation of a microenvironment favouring tumor growth and
      progression. Therefore, it is imperative to explore the expression of miRNA and
      understand its relevance in lung cancer and development of anti-cancer strategies
      (anti - miRs, miR mimics and micro RNA sponges). In view of the above, the role
      of miRNA in lung cancer has been dissected and the associated mechanisms and
      pathways are discussed in this review.

PMID- 30102930
TI  - Omega-3 fatty acids and leukocyte-endothelium adhesion: Novel anti
      atherosclerotic actions.
AB  - Endothelial cells (ECs) play a role in the optimal function of blood vessels.
      When endothelial function becomes dysregulated, the risk of developing
      atherosclerosis increases. Specifically, upregulation of adhesion molecule
      expression on ECs promotes the movement of leukocytes, particularly monocytes,
      into the vessel wall. Here, monocytes differentiate into macrophages and may
      become foam cells, contributing to the initiation and progression of an
      atherosclerotic plaque. The ability of omega-3 (n-3) polyunsaturated fatty acids
      (PUFAs) to influence the expression of adhesion molecules by ECs and to modulate
      leukocyte-endothelial adhesion has been studied in cell culture using various
      types of ECs, in animal feeding studies and in human trials; the latter have
      tended to evaluate soluble forms of adhesion molecules that circulate in the
      bloodstream. These studies indicate that n-3 PUFAs (both eicosapentaenoic acid
      and docosahexaenoic acid) can decrease the expression of key adhesion molecules,
      such as vascular cell adhesion molecule 1, by ECs and that this results in
      decreased adhesive interactions between leukocytes and ECs. These findings
      suggest that n-3 PUFAs may lower leukocyte infiltration into the vascular wall,
      which could contribute to reduced atherosclerosis and lowered risk of
      cardiovascular disease.

PMID- 30102931
TI  - Exploring receptor selectivity of the chimeric relaxin family peptide R3/I5 by
      incorporating unnatural amino acids.
AB  - Relaxin family peptides perform a variety of biological functions by activating
      four G protein-coupled receptors, namely RXFP1-4. Our recent study demonstrated
      that selectivity of the chimeric relaxin family peptide R3/I5 towards the
      homologous RXFP3 and RXFP4 can be modulated by replacement of the highly
      conserved nonchiral B23Gly or B24Gly with some natural l-amino acids. To
      investigate the mechanism of this modulating effect, in the present study we
      incorporated unnatural amino acids into the B23 or B24 position of a semi
      synthetic R3/I5 that was prepared by a novel sortase-catalysed ligation approach
      using synthetic relaxin-3 B-chain and recombinant INSL5 A-chain. R3/I5 was a weak
      agonist for RXFP3 after B23Gly was replaced by D-Ala or D-Ser, but a strong
      antagonist for this receptor after B23Gly was replaced by corresponding l-amino
      acids. However, these replacements always resulted in a weak agonist for RXFP4.
      Thus, configuration of the B23 residue of R3/I5 affected activation of RXFP3 but
      not RXFP4. For the B24 residue, both size and configuration affected receptor
      selectivity of R3/I5. l-amino acids with an appropriate size, such as L-Ser and L
      Abu, had the greatest effect on increasing the selectivity of R3/I5 towards RXFP3
      over the homologous RXFP4. Our present results provided new insights into
      receptor selectivity of R3/I5, and would facilitate design of novel agonists or
      antagonists for RXFP3 and RXFP4 in future studies.

PMID- 30102932
TI  - A chronic LPS-induced low-grade inflammation fails to reproduce in lean mice the
      impairment of preference for oily solution found in diet-induced obese mice.
AB  - Diet-induced obesity (DIO) is associated with a decreased oral fat detection in
      rodents. This alteration has been explained by an impairment of the lipid
      mediated signaling in taste bud cells (TBC). However, factors responsible for
      this defect remain elusive. Diet rich in saturated fatty acids is known to elicit
      a metabolic inflammation by promoting intestinal permeation to
      lipopolysaccharides (LPS), Gram-negative bacteria-derived endotoxins. To
      determine whether a local inflammation of the gustatory tissue might explain the
      obese-induced impairment of the oro-sensory detection of lipids, mice were
      subjected to a DIO protocol. Using a combination of behavioral tests,
      transcriptomic analyses of gustatory papillae and biochemical assays, we have
      found that i) DIO elicits a pro-inflammatory genic profile in the circumvallate
      papillae (CVP), known to house the highest density of lingual taste buds, ii)
      NFkB, a key player of inflammatory process, might play a role in this
      transcriptomic pattern, iii) plasma LPS levels are negatively correlated with the
      preference for oily solution, and iv) a chronic infusion of LPS at a level
      similar to that found in DIO mice is not sufficient to alter the spontaneous
      preference for fat in lean mice. Taken together these data bring the
      demonstration that a saturated high fat diet elicits an inflammatory response at
      the level of peripheral gustatory pathway and a LPS-induced low-grade endotoxemia
      alone does not explain the change in the preference for dietary lipids observed
      in DIO mice.

PMID- 30102933
TI  - Towards the development of robot immune system: A combined approach involving
      innate immune cells and T-lymphocytes.
AB  - Mobile robots in uncertain and unstructuredenvironments frequently encounter
      faults. Therefore, an effective fault detection and recovery mechanism is
      required. One can possibly investigate natural systems to seek inspiration to
      develop systems that can handle such faults. Authors, in this pursuit, have
      explored the possibility of designing an artificial immune system, called Robot
      Immune System (RIS), to maintain a robot's internal health-equilibrium. This
      contrasts with existing approaches in which specific robotic tasks are performed
      instead of developing a self-healing robot. In this respect, a fault detection
      and recovery methodology based on innate and adaptive immune functions has been
      successfully designed and developed. The immuno-inspired methodology is applied
      to a simulated robot using Robot Operating System and Virtual Robot
      Experimentation Platform. Through extensive simulations in increasingly difficult
      scenarios, the RIS has proven successful in autonomously detecting the abnormal
      behaviors, performing the recovery actions, and maintaining the homeostasis in
      the robot. In addition to being multi-tiered, the developed RIS is also a non
      deterministic and population-based system.

PMID- 30102935
TI  - IgD-activated mast cells induce IgE synthesis in B cells in nasal polyps.
AB  - BACKGROUND: Although upregulated expression of local IgD has been reported in
      patients with chronic rhinosinusitis (CRS), its function is unclear. OBJECTIVE:
      We sought to explore the expression and function of soluble IgD in patients with
      CRS, particularly CRS with nasal polyps. METHODS: IgD levels in sinonasal mucosa
      were analyzed by using RT-PCR and ELISA. Numbers and phenotypes of IgD+ cells
      were studied by means of immunohistochemistry, immunofluorescence, and flow
      cytometry. HMC-1 cells, a human mast cell line, and mast cells purified from
      eosinophilic polyps were cultured alone or with naive B cells purified from
      peripheral blood. The antigen specificity of nasal IgD was investigated by using
      ELISA. RESULTS: The mRNA expression of immunoglobulin heavy constant delta gene,
      numbers of IgD+ cells, and protein levels of secretory IgD in sinonasal mucosa
      were increased in patients with CRS with or without nasal polyps compared with
      control subjects. Numbers of IgD+ plasmablasts were increased in both
      eosinophilic and noneosinophilic polyps, whereas numbers of IgD+ mast cells were
      only increased in eosinophilic polyps. Cross-linking IgD induced serum
      preincubated HMC-1 cells and polyp mast cells to produce B-cell activating
      factor, IL-21, IL-4, and IL-13 and to promote IgM, IgG, IgA, and IgE production
      from B cells. In eosinophilic polyps expression of those B cell-stimulating
      factors in mast cells and close contact between mast cells and B cells were
      found. Moreover, positive correlations of total IgD levels with total IgE levels
      and eosinophilia and upregulation of specific IgD against house dust mites were
      discovered in eosinophilic polyps. CONCLUSION: IgD-activated mast cells can
      facilitate IgE production and eosinophilic inflammation in patients with CRS with
      nasal polyps.

PMID- 30102936
TI  - Allergen-specific sublingual immunotherapy is dose and duration dependent in a
      murine allergic rhinitis model.

PMID- 30102934
TI  - ERP indices of performance monitoring and feedback processing in psychosis: A
      meta-analysis.
AB  - BACKGROUND: Although individuals with, or at risk for, psychotic disorders often
      show difficulties with performance monitoring and feedback processing, findings
      from studies using event-related potentials (ERPs) to index these processes are
      not consistent. This meta-analytic review focused on studies of two different
      indexes of performance monitoring, the early error-related negativity (ERN; n =
      25) and the later error positivity (Pe; n = 17), and one index of feedback
      processing, the feedback negativity (FN; n = 6). METHODS: We evaluated whether
      individuals (1) with psychotic disorders, or (2) at heightened risk for these
      disorders differ from healthy controls in available studies of the ERN, Pe, and
      FN. RESULTS: There was a significant, large ERN reduction in those with psychosis
      (g = -0.96) compared to controls, and a significant, moderate ERN reduction in
      those at-risk (g = -0.48). In contrast, there were uniformly non-significant,
      small between-group differences for Pe and FN (gs <= |0.16|). CONCLUSIONS: The
      results reveal a differential pattern of impairment in psychosis. Early
      performance monitoring (ERN) impairments are substantial among those with
      psychotic disorders in general and may be a useful vulnerability indicator for
      these disorders. However, later performance monitoring (Pe) and basic feedback
      processing (FN) appear to be relatively spared in psychosis.

PMID- 30102937
TI  - Low-level ozone has both respiratory and systemic effects in African American
      adolescents with asthma despite asthma controller therapy.

PMID- 30102938
TI  - Genetic association between HLA-G 14-bp polymorphism and diseases: A systematic
      review and meta-analysis.
AB  - BACKGROUND: HLA-G is an immune checkpoint molecule. Since a differential molecule
      expression has been reported even for healthy individuals, many studies have
      focused on polymorphisms at HLA-G regulatory regions, particularly the 3'
      untranslated region (3'UTR). The presence/absence of a 14-bp sequence was the
      first polymorphism described and it is the most studied in association between
      HLA-G and disorders. METHODS: In this study, we performed a systematic review and
      meta-analysis of all association studies published regarding the HLA-G 14-bp.
      RESULTS: We verified association between 14-bp alleles and diseases in the
      following situations: (1) presence of 14-bp (insertion) conferred susceptibility
      to preeclampsia (child alleles evaluated) and systemic lupus erythematosus (OR =
      1.42; 95%CI = 1.04-1.93; p = 0.026 and OR = 1.13; 95%CI = 1.01-1.27, p = 0.028);
      (2) 14-bp absence (deletion) was associated with increased risk to breast cancer
      (OR = 1.23; 95%CI = 1.06-1.43; p = 0.006) and human Cytomegalovirus infection (OR
      = 2.06; 95%CI = 1.60-2.64; p < 0.0001); and (3) a risk association was observed
      between the group of reproductive disorders and the 14-bp insertion (OR = 1.12;
      95%CI = 1.01-1.24; p = 0.034). CONCLUSIONS: Considering that others 14-bp
      associations were inconclusive and that other variation sites observed at HLA-G
      3'UTR exhibit a proven role on post-transcriptional regulation of HLA-G
      expression, the complete 3'UTR segment should be analyzed in terms of disease
      susceptibility, instead of a single polymorphism.

PMID- 30102939
TI  - Role of membrane environment and membrane-spanning protein regions in assembly
      and function of the Class II Major Histocompatibility complex.
AB  - Class II Major Histocompatibility complex (MHC-II) is a polymorphic heterodimer
      that binds antigen-derived peptides and presents them on the surface of antigen
      presenting cells. This mechanism of antigen presentation leads to recognition by
      CD4 T-cells and T-cell activation, making it a critical element of adaptive
      immune response. For this reason, the structural determinants of MHC-II function
      have been of great interest for the past 30 years, resulting in a robust
      structural understanding of the extracellular regions of the complex. However,
      the membrane-localized regions have also been strongly implicated in protein
      protein and protein-lipid interactions that facilitate Class II assembly,
      transport and function, and it is these regions that are the focus of this
      review. Here we describe studies that reveal the strong and selective
      interactions between the transmembrane domains of the MHC alpha, and invariant
      chains which, when altered, have broad reaching impacts on antigen presentation
      and Class II function. We also summarize work that clearly demonstrates the link
      between membrane lipid composition (particularly the presence of cholesterol) and
      MHC-II conformation, subsequent peptide binding, and downstream T-cell
      activation. We have integrated these studies into a comprehensive view of Class
      II transmembrane domain biology.

PMID- 30102940
TI  - Insertion-responsive microneedles for rapid intradermal delivery of canine
      influenza vaccine.
AB  - In this study, we present transcutaneous influenza vaccination using a novel tip
      separable microneedle system called insertion-responsive microneedles (IRMNs).
      IRMNs are composed of dissolvable hyaluronic acid (HA) tips and biocompatible
      polycaprolactone (PCL) bases, the tip of which is instantly separated from the
      base during microneedle insertion and retraction. Vaccine antigens derived from
      canine influenza virus (A/canine/VC378/2012; H3N2) were successfully coated on HA
      tips by rapidly freezing the tips prior to coating. An ex vivo porcine skin
      insertion test showed that IRMNs were capable of penetrating the skin without tip
      breakage and releasing the coated materials within the skin. The thermal
      stability of the vaccine as determined by hemagglutination assay revealed that
      the coated vaccine partially maintained its activity when stored at 50  degrees C
      for 3 weeks, whereas the liquid form completely lost the activity. Immunization
      in guinea pigs showed that hemagglutination inhibition (HI) antibodies induced by
      IRMNs were two times higher than those induced by intramuscular (IM) injections.
      When challenged with influenza A/canine/Korea/01/2007 (H3N2) wild-type virus 2
      weeks after the second vaccination, viral shedding was completely eliminated at 8
      days post infection in both IRMNs and IM injection groups. Our results suggest
      that IRMNs have great potential for rapid and convenient vaccination, which will
      be particularly attractive for animal vaccinations.

PMID- 30102941
TI  - Triintsin, a human pathogenic fungus-derived defensin with broad-spectrum
      antimicrobial activity.
AB  - Since there is a symbiotic and competitive relationship between microorganisms in
      the same ecological niche, fungal defensins have been found to be important
      resources for antimicrobial peptides. Here, a fungal defensin, triintsin, was
      characterized in a clinical isolate of Trichophyton interdigitale from a patient
      with onychomycosis. The comparison of its genomic and mRNA sequences showed the
      gene organization and structure of three coding exons separated by two introns.
      The precursor peptide of triintsin contained 85 amino acid residues, which were
      composed of three parts including an N-terminal signal domain of 21 residues, a
      pro-peptide of 47 residues that ended at lysine-arginine and a mature peptide of
      38 residues at the C-terminus. The 3D-structure established by homology modeling
      revealed that triintsin presented a representative typical cysteine-stabilized
      alpha-helical and beta-sheet fold. The reductive linear peptide of triintsin was
      obtained by chemical synthesis. After cyclization to form three pairs of
      disulfide bonds, the oxidative-type peptide displayed broad-spectrum
      antimicrobial activity against both gram-positive and gram-negative bacteria but
      also showed anti-fungal activity. Moreover, triintsin can effectively inhibit the
      growth of clinical strains. Altogether, the peptide is a human pathogenic fungus
      derived defensin with broad-spectrum antimicrobial activity.

PMID- 30102942
TI  - Factors related to vegetable intake among pregnant Japanese women: A cross
      sectional study.
AB  - INTRODUCTION: Vegetable intake (VI) is important for both fetal and maternal
      health. However, VI is insufficient among many pregnant Japanese women. This
      study aimed to identify the factors related to VI during pregnancy. METHODS: A
      cross-sectional study was conducted in 2014, at a university hospital in Tokyo,
      Japan. Dietary intake was assessed using a brief-type self-administered diet
      history questionnaire. Demographic, physical, and psychological characteristics,
      dietary habits, and health-related behaviors were investigated using another
      questionnaire. Multiple linear regression analysis was used to identify factors
      related to VI. RESULTS: Data of 273 healthy pregnant women was analyzed. The
      median value of energy-adjusted VI was 140.4 g/1000 kcal. Severe pregnancy
      associated nausea (beta = -0.148), a habit of eating out (beta = -0.174), a habit
      of eating confectioneries (beta = -0.158), and perceived barriers to obtaining
      vegetables (beta = -0.149) were negatively associated with the energy-adjusted
      VI. In contrast, exercise habits (beta = 0.193), knowledge of the recommended VI
      amounts for non-pregnant adults (beta = 0.105), and the Vegetable Intake Self
      Efficacy scale scores (beta = 0.193) were positively associated with the energy
      adjusted VI. CONCLUSIONS: Pregnant women with severe pregnancy-associated nausea,
      or those who habitually eat out or eat confectioneries, may be a potential high
      risk population for low VI. Enhancing knowledge and self-efficacy regarding VI
      would be effective in increasing VI during pregnancy.

PMID- 30102943
TI  - Does immersion or detachment facilitate healthy eating? Comparing the effects of
      sensory imagery and mindful decentering on attitudes and behavior towards healthy
      and unhealthy food.
AB  - Many people would like to reduce indulging in unhealthy foods, but find it
      difficult to do so. Previous research shows that individuals eat smaller portions
      of unhealthy hedonic food if they first imagine the sensory properties of
      tempting food (sensory imagery; Cornil & Chandon, 2016). Similarly, they show
      less preference for such food if they think about food in a detached way
      (decentering; Papies, Barsalou, & Custers, 2012; Papies, Pronk, Keesman, &
      Barsalou, 2015). Given that these two mindsets are seemingly at odds with each
      other, we compared them across two studies to examine their effects on the
      preference for (Experiment 1) and consumption of (Experiment 2) hedonic healthy
      and unhealthy food. Although sensory imagery and decentering had largely
      different effects for preferences towards healthy and unhealthy foods, they had
      comparable effects on the consumption of both types of foods, serving to reduce
      the effects of consumption in participants affected by hunger and emotional
      eating. These results suggest that while sensory imagery and decentering are
      based on different mechanisms, they produce similar results when it comes to the
      consumption of hedonic food, regardless of how healthy the food is.

PMID- 30102944
TI  - MRSA colonization status as a predictor of clinical infection: A systematic
      review and meta-analysis.
AB  - BACKGROUND: Vancomycin is often used as empiric therapy for methicillin-resistant
      Staphylococcus aureus (MRSA), but can be associated with clinically important
      adverse events including renal failure. MRSA colonization swabs are primarily
      used for infection control; their use as a diagnostic test to inform the decision
      to add empiric vancomycin therapy has not been well elucidated. METHODS: We
      performed a Medline and Embase systematic review for peer-reviewed studies
      reporting the diagnostic accuracy of using MRSA colonization status to predict
      MRSA infections. Meta-analysis was performed using Cochrane guidelines. Grey
      literature was excluded. FINDINGS: 29 studies were included involving 24225
      patients. In cases where the pathogen is not known to be S. aureus, specificities
      were greater than 85% for bacteremia, lower respiratory tract infections, skin
      and soft tissue infections (SSTI), and all infections pooled together.
      Sensitivities ranged between 54.0% and 77.5%. In cases where the pathogen is
      known to be S. aureus, we found studies on bacteremia and SSTI and arrived at
      pooled estimates of sensitivities ranging between 56.6% and 56.9%, and of
      specificities greater than 91%. Most importantly, for most infections in settings
      where the prevalence of MRSA as a causative organism is below 15%, the negative
      predictive value of a negative MRSA colonization swab exceeds 90%.
      INTERPRETATIONS: In settings of low-moderate MRSA prevalence, negative MRSA
      screening swabs may prevent unnecessary vancomycin use. More research is needed
      to assess if this strategy can mitigate the cost of screening in areas with a low
      MRSA colonization rate.

PMID- 30102946
TI  - l-Dopa treatment during perinatal development leads to different behavioral
      alterations in female vs. male juvenile Swiss mice.
AB  - Alterations in dopaminergic signaling and neurodevelopment are associated with
      many neuropsychiatric disorders, such as attention deficit and hyperactivity
      disorder (ADHD), autism, and schizophrenia. Imbalances in dopamine levels during
      prenatal development are associated with behavioral alterations later in life,
      like hyperactivity and addiction, and it is possible that dopaminergic imbalances
      may have diverse effects during different neurodevelopmental windows. In this
      study, we investigate whether an increase in dopamine levels during the perinatal
      developmental window affects behavior of juvenile male and female Swiss mice. In
      order to do so, we intraperitoneally administered daily doses of l-Dopa to mice
      pups beginning from postnatal day 1 (PD1) to PD5, which increased the levels of
      dopamine and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), in the
      striatum of the pups. At the age of 4 weeks, we submitted the juvenile males and
      females to the open field test, elevated plus maze, forced swimming test, and
      sucrose preference test. We observed that increase of dopamine levels during the
      perinatal developmental window increased exploratory behavior in juvenile
      females, but not males. We observed no changes in anxiety- and depressive-like
      behaviors. In contrast, we observed that increased dopamine levels during the
      perinatal period lead to hedonic alterations in juvenile males, but not females.
      Our results show that dopamine signaling is important for behavioral development
      and that transient imbalance of dopamine levels causes juvenile behavioral
      alterations, which are different in males than in females. These data may help in
      better understanding the spectrum of symptoms associated with different
      neuropsychiatric disorders.

PMID- 30102947
TI  - Comment on "Impact of air manganese on child neurodevelopment in East Liverpool,
      Ohio," by Haynes et al. (2018).

PMID- 30102945
TI  - Epigenetic modification enhances the cytotoxicity of busulfan and4
      hydroperoxycyclophosphamide in AML cells.
AB  - The combination of the DNA-alkylating agents busulfan (Bu) and cyclophosphamide
      is the most commonly used myeloablative pretransplantation conditioning therapy
      for myeloid leukemias. However, it is associated with significant nonrelapse
      mortality, which prohibits dose escalation to control relapse. We hypothesized
      that combining these two drugs with an epigenetic modifier would increase
      antileukemic efficacy without jeopardizing patient safety. A preclinical study
      was performed to determine the synergistic cytotoxicity of Bu, 4
      hydroperoxycyclophosphamide (4HC), and the hypomethylating agent decitabine (DAC)
      in human acute myeloid leukemia (AML) cell lines. Exposure of KBM3/Bu2506 (P53
      null) and OCI-AML3 (P53-wild-type) cells to Bu+4HC inhibited cell proliferation
      by ~35-39%; addition of DAC increased the inhibition to ~60-62%. The observed
      synergistic interactions correlated with DNA damage response activation,
      increased the production of reactive oxygen species, and decreased mitochondrial
      membrane potential, release of mitochondrial proapoptotic proteins into the
      cytoplasm, and induction of caspase-dependent programmed cell death. The
      Bu+4HC+DAC combination further caused chromatin trapping of DNMT1 with a
      concomitant increase in DNA damage. In contrast, FMS-like tyrosine kinase 3
      internal tandem duplications (FLT3-ITD)-positive AML cell lines were not
      sensitized to Bu+4HC by inclusion of DAC; addition of the FLT3 kinase inhibitor
      sorafenib sensitized the FLT3-ITD-positive MV4-11 and MOLM13 cell lines to the
      triple drug combination by inhibiting the FLT3 signal transduction pathway. Our
      results therefore provide a rationale for the development of personalized
      conditioning therapy for patients with P53-mutated and FLT3-ITD-positive AML.

PMID- 30102948
TI  - Carbapenemase-producing Enterobacteriaceae in Australian hospitals: outcome of
      point-prevalence screening in high-risk wards.
AB  - Carbapenemase-producing Enterobacteriaceae (CPE) infections are increasingly
      reported in Australian hospitals, but prevalence is unknown. In 2016, Victorian
      hospitals conducted CPE point-prevalence surveys in high-risk wards (intensive
      care, haematology, transplant). Forty-three hospitals performed 134 surveys, with
      1839/2342 (79%) high-risk patients screened. Twenty-four surveys were also
      performed in other wards. Inability to obtain patient consent was the leading
      reason for non-participation. In high-risk wards, no CPE cases were detected;
      three cases were identified in other wards. Since there is low prevalence in high
      risk wards, continuous screening is not recommended. Targeted screening may be
      enhanced by review of patient consent processes.

PMID- 30102950
TI  - Angioinvasive Fungal Infections Impacting the Skin: Diagnosis, Management, and
      Complications (Part 2).
AB  - As discussed in Part I, angioinvasive fungal infections pose a significant risk
      to immunocompromised and immunocompetent patients alike,1 with potential for
      severe morbidity and high mortality. Part I of this CME focused on the
      epidemiology and clinical presentation of these infections; Part II will discuss
      diagnosis, management, and potential complications of these infections. The
      mainstay diagnostic tests (positive tissue culture with histologic confirmation)
      are often supplemented with serum biomarker assays and molecular testing (e.g.,
      quantitative PCR analysis and MALDI-TOF mass spectrometry) to ensure proper
      speciation. When an angioinvasive fungal infection is suspected or diagnosed,
      further work-up for visceral involvement also is essential and may partially
      depend on the organism. Different fungal organisms demonstrate varied
      susceptibilities to antifungal agents, and knowledge on optimal treatment
      regimens is important to avoid potential complications associated with
      undertreated or untreated fungal infections.

PMID- 30102949
TI  - Pyrethroid bifenthrin induces oxidative stress, neuroinflammation, and neuronal
      damage, associated with cognitive and memory impairment in murine hippocampus.
AB  - Exposure to synthetic pyrethroid (SPs) pesticides such as bifenthrin (BF) has
      been associated with adverse neurodevelopmental outcomes and cognitive
      impairments, but the underlying neurobiological mechanism is poorly understood so
      far. The present study has been designed to evaluate changes in behavior and in
      biomarkers of oxidative stress and neuroinflammation in the hippocampus of rats
      subchronically treated with BF. Rats exposed daily to BF at doses of 0.6 and 2.1
      mg/kg b. w. for 60 days exhibited spatial and cognitive impairments as well as
      memory dysfunction after 60 days. This repeated BF treatment also significantly
      increased mRNA expression of pro-inflammatory cytokines tumor necrosis factor
      (TNF-alpha), interleukin (IL-1beta), (IL-6), nuclear factor erythroid-2 (Nrf2),
      cyclooxygenase-2 (COX-2), nuclear factor-kappaB pathway (NF-kappaB), and
      prostaglandin E2 (PGE2) in the hippocampus. It further resulted in a significant
      increase in protein levels of Nrf2, COX-2, microsomal prostaglandin synthase-1
      (mPGES-1) and NF-kappaB. This was accompanied by oxidative/nitrosative stress in
      the hippocampus of treated rats, as shown by increased levels of malondialdehyde
      (MDA), protein carbonyls (PCO), and nitric oxide (NO), and reduced levels of
      enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) and non
      enzymatic (reduced glutathione) antioxidants. The data are in line with those
      obtained in organotypic hippocampal slice cultures (OHSCs) isolated from mouse
      brain and exposed to BF for 72 h, showing neuronal death only at the high dose of
      20 MUM when compared to controls. These findings suggest that exposure to BF
      induces neuronal damage, alters redox state, and causes neuroinflammation in the
      hippocampus, which might lead to cognitive and memory impairment.

PMID- 30102951
TI  - Angioinvasive Fungal Infections Impacting the Skin: Background, Epidemiology, and
      Clinical Presentation (Part 1).
AB  - Angioinvasive fungal infections cause significant morbidity and mortality due to
      their propensity to invade blood vessel walls, resulting in catastrophic tissue
      ischemia, infarct, and necrosis. While occasionally seen in immunocompetent
      hosts, opportunistic fungi are emerging in immunosuppressed hosts, including
      patients with hematologic malignancy, acquired immunodeficiency syndrome (AIDS),
      organ transplant, and poorly controlled diabetes mellitus. The widespread use of
      antifungal prophylaxis has led to an "arms race" of emerging fungal resistance
      patterns. As the at-risk population expands and as new anti-fungal resistance
      patterns develop, it is critical for dermatologists to understand and recognize
      angioinvasive fungal pathogens, as they are often the first to encounter the
      cutaneous manifestations of these diseases. Rapid clinical recognition,
      histopathologic, and culture confirmation can help render a timely, accurate
      diagnosis to ensure immediate medical and surgical intervention. As superficial
      dermatophyte infections and deep fungal infections such as blastomycosis and
      histoplasmosis have been well characterized within the dermatologic literature,
      this article will focus on the severe infections acquired by angioinvasive fungal
      species, including an update on new and emerging pathogens. In part 1 of this
      series, we review the epidemiology and cutaneous manifestations, and part 2 will
      focus on diagnosis, treatment, and complications of these infections.

PMID- 30102952
TI  - Exosomal transfer of miR-151a enhances chemosensitivity to temozolomide in drug
      resistant glioblastoma.
AB  - Chemoresistance blunts the effect of Temozolomide (TMZ) in the treatment of
      glioblastoma multiforme (GBM). Whether exosomal transfer of miRNAs derived from
      TMZ-resistant GBM cells could confer TMZ resistance remains to be determined.
      qPCR was used to determine miR-151a expression in two TMZ-resistant GBM cell
      lines. The direct targets of miR-151a were identified by microarray assays,
      bioinformatics and further RNA chromatin immunoprecipitation (RNA-ChIP) assay. We
      characterized exosomes from TMZ-resistant cell lines, serum and cerebrospinal
      fluid (CSF) and determined the effect of exosomes from TMZ-resistant cells on
      recipient GBM cells. miR-151a loss drove the acquisition of TMZ resistance.
      Restored miR-151a expression sensitized TMZ-resistant GBM cells via inhibiting
      XRCC4-mediated DNA repair. TMZ-resistant GBM cells conferred TMZ chemoresistance
      to recipient TMZ-sensitive cells in an exosomal miR-151a loss-dependent manner.
      Restoration of exosomal miR-151a from donor TMZ-resistant cells abolished the
      chemoresistance dissemination that was directed by donor TMZ-resistant cells. CSF
      derived exosomes contained miRNA signatures reflective of the underlying
      chemoresistant status of GBMs in terms of miR-151a expression levels. Exosomal
      miR-151a is not only essentially a less-invasive 'liquid biopsy' that might
      predict chemotherapy response, but also represents a promising therapeutic target
      for therapy-refractory GBMs.

PMID- 30102954
TI  - A non-reflexive method based on the variability of temperature and bioimpedance
      in measuring inflammatory hyperalgesia and analgesia in mice.
AB  - BACKGROUND: Preclinical studies measure withdrawal responses to evoking thermal
      and mechanical stimuli instead of the more clinically important spontaneous pain.
      NEW METHOD: Therefore, we studied the effect of peripheral inflammation induced
      by intraplantar administration of complete Freund's adjuvant (CFA) in mice on the
      variability of temperature and bioimpedance as an index of pain produced by
      inflammation. To this end, we initially determined mathematical scores based on
      changes in temperature and bioimpedance (STB) for animals with an inflamed paw
      and compared these scores with commonly used measures of inflammatory pain. We
      then pharmacologically validated the tool using dexamethasone. RESULTS: The STB
      analysis resembled the response found in the von Frey Hair (vFH) test. The CFA
      induced increase in STB and vFH tests were reversed by intraperitoneal
      administration of dexamethasone. The correlation between the STB and vFH
      measurements showed a high correlation coefficient (R2 = 0.911, p <  0.001).
      COMPARISON WITH EXISTING METHOD: Our results also demonstrated that CFA paw
      injection induced mechanical hyperalgesia in mice and remained virtually
      unaltered during all time-points tested for 5 days, as measured with vFHs. The
      administration of CFA into the paw induced a large increase in paw volume that
      was apparent 1 and 5 days after the injection. The CFA injection resulted in a
      significant (p < 0.05) decrease in the response latency to the heat stimulus, as
      evaluated on day 4 post-CFA injection. CONCLUSIONS: The data presented here
      suggest that STB may provide a novel non-invasive approach for inflammatory pain
      detection.

PMID- 30102955
TI  - CEPO-Fc (An EPO Derivative) Protects Hippocampus Against Abeta-induced Memory
      Deterioration: A Behavioral and Molecular Study in a Rat Model of Abeta Toxicity.
AB  - Alzheimer's disease (AD) is a debilitating neurodegenerative disease,
      characterized by extracellular deposition of senile plaques, mostly amyloid beta
      protein (Abeta) and neuronal loss. The neuroprotective effects of erythropoietin
      (EPO) have been reported in some models of neurodegenerative disease, but because
      of its hematopoietic side effects, its derivatives lacking hematopoietic
      bioactivity is recommended. In this study, the neuroprotective effects of
      carbamylated erythropoietin-Fc (CEPO-Fc) against beta amyloid-induced memory
      deficit were evaluated. Adult male Wistar rats weighing 250-300 g were
      bilaterally cannulated into CA1. Abeta25-35 was administered intrahippocampally
      for 4 consecutive days (5 MUg/2.5 MUL/each side/day). CEPO-Fc (500 or 5000 IU)
      was injected intraperitoneally during days 4-9. Learning and memory performance
      of rats was assessed on days 10-13 using Morris Water Maze, then hippocampi were
      isolated and the amount of activated forms of hippocampal MAPKs' subfamily,
      Akt/GSK-3beta and MMP-2 were analyzed using Western blot. From the behavioral
      results, it was revealed that CEPO-Fc treatment in both 500 and 5000 IU
      significantly reversed Abeta-induced learning and memory deterioration. From the
      molecular analysis, an increment of MAPKs and MMP-2 activity and an imbalance in
      Akt/GSK-3beta signaling after Abeta25-35 administration was observed. CEPO-Fc
      treatment prevented the elevation of hippocampal of P38, ERK, MMP-2 activity and
      also Akt/GSK-3beta signaling impairment induced by Abeta25-35 but it had no
      effect on JNK. It seems that CEPO-Fc prevents Abeta-induced learning and memory
      deterioration, and also modulates hippocampal MAPKs, Akt/GSK-3beta and MMP-2
      activity. This study suggests that CEPO-Fc can be considered as a potential
      therapeutic strategy for memory deficits like AD.

PMID- 30102956
TI  - Abnormalities in Prefrontal Cortical Gene Expression Profiles Relevant to
      Schizophrenia in MK-801-Exposed C57BL/6 Mice.
AB  - MK-801, a non-competitive NMDA receptor (NMDAR) antagonist, disturbs NMDAR
      function in rodents and induces psychological and behavioral changes similar to
      schizophrenia (SCZ). However, the effects of MK-801 treatment on gene expression
      are largely unknown. Here we performed RNA-sequencing on the prefrontal cortex of
      MK-801-exposed male mice in order to analyze gene expression and co-expression
      patterns related to SCZ and to identify mechanisms that underlie the molecular
      etiology of this disorder. Transcriptome analysis revealed that the
      differentially expressed genes were more often associated with biological
      processes that included postsynaptic transmission, immune system process,
      response to external stimulus and hemostasis. In order to extract comprehensive
      biological information, we used an approach for biclustering, called FABIA, to
      simultaneously cluster transcriptomic data across genes and conditions. When
      combined with analyses using DAVID and STRING databases, we found that co
      expression patterns were altered in synapse-related genes and genes central to
      the mitochondrial network. Abnormal co-expression of genes mediating synaptic
      vesicle cycling could disturb release, uptake and reuptake of glutamate, and the
      perturbation in co-expression patterns for mitochondrial respiratory chain
      complexes was extensive. Our study supports the hypothesis that research using MK
      801-exposed male mice as an animal model of SCZ offers important insights into
      the pathogenesis of SCZ.

PMID- 30102953
TI  - Fatty acid oxidation: An emerging facet of metabolic transformation in cancer.
AB  - Cancer cells undergo metabolic reprogramming such as enhanced aerobic glycolysis,
      mutations in the tricarboxylic acid cycle enzymes, and upregulation of de novo
      lipid synthesis and glutaminolysis. These alterations are pivotal to the
      development and maintenance of the malignant phenotype of cancer cells in
      unfavorable tumor microenvironment or metastatic sites. Although mitochondrial
      fatty acid beta-oxidation (FAO) is a primary bioenergetic source, it has not been
      generally recognized as part of the metabolic landscape of cancer. The last few
      years, however, have seen a dramatic change in the view of cancer relevance of
      the FAO pathway. Many recent studies have provided significant evidence to
      support a "lipolytic phenotype" of cancer. FAO, like other well-defined metabolic
      pathways involved in cancer, is dysregulated in diverse human malignancies.
      Cancer cells rely on FAO for proliferation, survival, stemness, drug resistance,
      and metastatic progression. FAO is also reprogrammed in cancer-associated immune
      and other host cells, which may contribute to immune suppression and tumor
      promoting microenvironment. This article reviews and puts into context our
      current understanding of multi-faceted roles of FAO in oncogenesis as well as
      anti-cancer therapeutic opportunities posed by the FAO pathway.

PMID- 30102957
TI  - Protection of manganese oxide nanoparticles-induced liver and kidney damage by
      vitamin D.
AB  - Metal nanoparticles (NPs) have been extensively used in industry as well as in
      biomedical application. Manganese oxide-nanoparticles (MnO2-NPs) one of these
      materials, have many applications. This study was designed to evaluate the
      protective role of vitamin D against MnO2-NPs -induced toxicity in the BALB c
      mice. These mice were randomly assigned to 4 (n = 10). In this study, MnO2-NPs
      (10 mg/kg), vitamin D (10 mg/kg) and MnO2-NPs plus vitamin D were administered
      interperitoneally once daily for 50 consecutive days. The liver and kidney
      functions, the levels of serum glucose, albumin (ALB), bilirubin (BIL) and total
      protein were studied. The results indicated that MnO2-NPs administration
      significantly decreased liver and kidney functions, and increased glucose and
      bilirubin serum levels compared to control group (P < 0.05). However, vitamin D
      administration significantly boosted liver and kidney functions, decreased
      glucose and bilirubin serum level compared to the group received MnO2-NPs (P <
      0.05). It seems that vitamin D administration could protect the liver and kidney
      damage induced by MnO2-NPs. Probably, given the use of these nanoparticles as a
      contest agent in humans, having normal levels of vitamin D or receiving it at the
      time of the test can inhibit liver and kidney toxicity induced by MnO2-NPs.

PMID- 30102958
TI  - Increased incidence of herpes zoster in patients on renal replacement therapy
      cannot be explained by intrinsic defects of cellular or humoral immunity to
      varicella-zoster virus.
AB  - BACKGROUND: Patients in need of long-term renal replacement therapy (RRT) are
      known to be at increased risk of herpes zoster, occurring when the latently
      present varicella-zoster virus (VZV) reactivates. In this study we investigated
      immunity to VZV in patients receiving RRT, with the aim of better understanding
      the mechanism behind the increased risk. METHODS: Patients treated for at least
      three months with hemodialysis or peritoneal dialysis, and matched healthy
      controls (HC) were included. Cellular immunity to varicella-zoster virus (VZV)
      was studied using an interferon-gamma (IFNgamma) enzyme-linked immunospot
      (ELISpot) assay, flow-cytometric analysis of cytokine production and a
      proliferation assay. Humoral immunity was determined by measuring immunoglobulin
      (Ig)G antibody levels to VZV using an in-house glycoprotein enzyme-linked
      immunosorbent assay (ELISA). Multiple regression was used to assess variables of
      influence on measures of cellular and humoral immunity to VZV in patients
      receiving RRT. RESULTS: Similar numbers of IFNgamma spot-forming cells and levels
      of VZV-IgG were found in 97 patients and 89 HC. Age and transplantation history
      were negatively associated with cellular immunity (p = 0.001 and p = 0.012,
      respectively) while treatment modality, gender and urea levels were not. No
      variables were found to be associated with VZV-IgG levels. CONCLUSIONS: Increased
      incidence of herpes zoster in patients receiving RRT cannot be explained by
      intrinsic defects of cellular or humoral immunity to VZV as measured by the
      methods used in this study, although older age and previous transplantation were
      associated with decreased cellular immunity to VZV. Herpes zoster susceptibility
      might be caused by a diminished function of otherwise capable T cells in a uremic
      environment.

PMID- 30102959
TI  - Ketamine modulates aggressive behavior in adult zebrafish.
AB  - Ketamine is a non-competitive glutamatergic antagonist that induces analgesia and
      anesthesia. Although ketamine displays anxiolytic and antidepressant properties,
      it may induce pro-psychosis and hallucinogen effects, as well as stereotypic
      behaviors following acute administration at sub-anesthetic doses. Since
      heightened aggression is maladaptive and may comorbid with various
      neuropsychiatric disorders, we aimed to investigate whether ketamine modulates
      aggressive behavior in adult zebrafish. Fish were acutely exposed to 2, 20, and
      40 mg/L ketamine for 20 min and their locomotion, exploratory activity, and
      aggression towards mirror were further assessed. Ketamine (2 mg/L) increased
      aggression-related phenotypes, while 20 and 40 mg/L reduced aggression and
      elicited stereotypic behaviors by causing hyperlocomotion, altering motor
      patterns, and increasing circling behavior at the higher concentration tested.
      Collectively, our data expand the utility of zebrafish models to investigate the
      influence of sub-anesthetic concentrations of ketamine on aggression behavior
      domain in translational neuropsychiatric research field.

PMID- 30102960
TI  - Positron emission tomography imaging of the gamma-aminobutyric acid system.
AB  - In this review, we summarize the recent development of positron emission
      tomography (PET) radioligands for gamma-aminobutyric acid A (GABAA) receptors and
      their potential to measure changes in endogenous GABA levels and highlight the
      clinical and translational applications of GABA-sensitive PET radioligands. We
      review the basic physiology of the GABA system with a focus on the importance of
      GABAA receptors in the brain and specifically the benzodiazepine binding site.
      Challenges for the development of central nervous system radioligands and
      particularly for radioligands with increased GABA sensitivity are outlined, as
      well as the status of established benzodiazepine site PET radioligands and
      agonist GABAA radioligands. We underline the challenge of using allosteric
      interactions to measure GABA concentrations and review the current state of PET
      imaging of changes in GABA levels. We conclude that PET tracers with increased
      GABA sensitivity are required to efficiently measure GABA release and that such a
      tool could be broadly applied to assess GABA transmission in vivo across several
      disorders.

PMID- 30102961
TI  - Impact of lincosamides antibiotics on the composition of the rat gut microbiota
      and the metabolite profile of plasma and feces.
AB  - The importance of the gut microorganisms and their wide range of interactions
      with the host are well-acknowledged. In this study, lincomycin and clindamycin
      were used to modulate microbial communities of Wistar rats to gain a
      comprehensive understanding of the implications of microbiome alterations. A
      metabolomics approach and taxonomic profiling were applied to characterize the
      effects of these antibiotics on the functionality of the microbiome and to
      identify microbiome-related metabolites. After treatment, the diversity of the
      microbial community was drastically reduced. Bacteroidetes and Verrucomicrobia
      were drastically reduced, Tenericutes and Deferribacteres completely disappeared,
      while abundance of Firmicutes and Proteobacteria were highly increased. Changes
      in plasma and feces metabolites were observed for metabolites belonging mainly to
      the class of complex lipids, fatty acids and related metabolites as well as amino
      acids and related compounds. Bile acid metabolism was markedly affected:
      taurocholic acid, glycochenodeoxycholic acid and cholic acid presented abrupt
      changes showing a specific metabolite pattern indicating disruption of the
      microbial community. In both plasma and feces taurocholic acid was highly
      upregulated upon treatment whereas glycochenodeoxycholic acid was downregulated.
      Cholic acid was upregulated in feces but downregulated in plasma. These results
      show that changes in the gut microbial community lead to alterations of the
      metabolic profile in blood and feces of the host and can be used to identify
      potentially microbiome-related metabolites. This implies that metabolomics could
      be a suitable tool to estimate the extent of changes induced in the intestinal
      microbiome with respect to consequences for the host.

PMID- 30102962
TI  - The anti-inflammatory effect of BML-111 on COPD may be mediated by regulating
      NLRP3 inflammasome activation and ROS production.
AB  - The aim of this study is to investigate whether the lipoxin receptor agonist BML
      111 exerts a protective effect against inflammation in a mouse model of chronic
      obstructive pulmonary disease (COPD) by regulating NLRP3 inflammasome activation
      and reactive oxygen species (ROS) production. In this study, mice were randomly
      divided into the following five groups: control group (Control), COPD model group
      (Model), BML-111 low-dose group (Low-BML), BML-111 high-dose group (High-BML) and
      Dexamethasone group (Dex). NLRP3 involvement and oxidative stress were evaluated.
      Differential cell counts in the BALF were calculated to obtain a reliable
      enumeration of each cell type, and the levels of TGF-beta, TNF-alpha, IL-1beta,
      and IL-10 in BALF were evaluated using ELISA. We found that the white blood cell
      and lymphocyte numbers in the BALF were significantly lower in the High-BML group
      than in the Model group. ELISA of the BALF showed that BML-111 reduced TGF-beta
      and IL-1beta levels to some extent. HE staining showed various degrees of
      reduction in inflammatory cell infiltration in the bronchopulmonary tissue and
      blood vessels of the Low-BML, High-BML and Dex groups. Measurement of oxidative
      stress showed that SOD activity was significantly upregulated and that the
      increase in MDA content was prevented in the High-BML and Dex groups. According
      to the Western blotting analysis, the levels of NLRP3, Cleaved-IL-1beta and
      Cleaved-caspase-1 were decreased and Nrf-2 was increased to various extents in
      the Low-BML, High-BML and Dex groups. Based on these findings, BML-111 may
      prevent NLRP3 inflammasome activation and inhibit ROS production via upregulation
      of Nrf-2, thereby exerting an anti-inflammatory effect on COPD model mice.

PMID- 30102963
TI  - Heart rate variability changes and its association with the development of severe
      retinopathy of prematurity.
AB  - PURPOSE: To evaluate differences in autonomic nervous system (ANS) activity
      associated with the development of retinopathy of prematurity. METHODS: Heart
      rate variability (HRV) as an indicator of ANS activity was calculated in two
      groups of premature infants: (1) a treatment group of infants who developed type
      1 ROP and underwent treatment and (2) a control group of infants who did not
      develop ROP more severe than stage 1 and who were matched to the treatment group
      in terms of age, weight, and similar risk factors, including similar frequency of
      intraventricular hemorrhage, bronchopulmonary dysplasia, and sepsis. HRV was
      analyzed during the first 5 days of life, within 5 days of initial ROP
      examination, and within 5 days of ROP treatment for the treatment group or, for
      controls, on the day of last electrocardiogram data prior to discharge.
      Calculations were performed for the high frequency, low frequency, and low
      frequency-high frequency values of the HRV components for all infants. RESULTS:
      Between the initial ophthalmologic evaluation and the final evaluation, there was
      a tendency for reduction in both the low- and high-frequency components of the
      HRV indices in the treatment group, whereas there was a tendency for an increase
      in both components of the HRV indices in the control group. The difference in the
      rate of change of the high frequency between groups was statistically significant
      (P = 0.021). CONCLUSIONS: Disruption in ANS activity may play an important role
      in the development and severity of ROP.

PMID- 30102964
TI  - A twenty-two-year experience with Hymenoptera venom immunotherapy in a US
      pediatric tertiary care center 1996-2018.
AB  - BACKGROUND: The rate of systemic reactions (SRs) to venom immunotherapy (VIT) in
      children has not been well evaluated. OBJECTIVE: To evaluate the rate of SRs to
      VIT in pediatric patients age 5 to 18 years who were treated with a standard
      protocol. METHODS: A retrospective chart review was conducted to identify
      patients who received VIT at Boston Children's Hospital from 1996 through 2018.
      Information on venom testing, severity of reaction to insect field sting, and SRs
      to VIT were retrieved. RESULTS: A total of 78 patients were included. Most had
      moderate to severe reactions to insect sting before VIT. The rate of SRs was 0.2%
      of injection visits, occurring in 9% of patients. The SRs from VIT were mild
      (mostly grade 1 and some grade 2), and no grades 3, 4, or 5 reactions were seen.
      Male sex was a significant risk factor for moderate to severe reactions to insect
      sting. Positive testing to vespinae was seen in 98.7% of patients, and none had
      exclusive sensitivity to honeybee. The severity of the initial, pre-VIT insect
      sting reactions in our patients did not correlate with the occurrence of SRs from
      VIT. Twenty-seven percent of the patients were subsequently stung while on VIT.
      Only 1 patient (5%) had a mild SR, while all others had only local or no reaction
      at all. CONCLUSION: In the largest US study evaluating the safety of VIT in
      children, SRs to VIT were mild, and none required epinephrine. Male sex was
      significantly associated with higher risk of moderate to severe reactions to
      insect sting. Larger multicenter studies are needed to further evaluate the rate
      of SRs to VIT in pediatric patients.

PMID- 30102965
TI  - A phase 2a study of toreforant, a histamine H4 receptor antagonist, in
      eosinophilic asthma.
AB  - BACKGROUND: Data from preclinical and clinical studies support the evaluation of
      histamine 4 receptor antagonists in the treatment of asthma. Toreforant is a
      selective histamine 4 receptor antagonist that could be effective in patients
      with eosinophilic asthma. OBJECTIVE: To evaluate the efficacy and safety of
      toreforant in patients with eosinophilic, persistent asthma that was inadequately
      controlled despite current treatment. METHODS: In this phase 2a, multicenter,
      randomized, double-blinded, parallel-group, placebo-controlled, proof-of-concept
      study, 162 eligible patients were randomized (1:1) to placebo or 30 mg of
      toreforant once daily through week 24 and followed for 4 weeks. The primary end
      point was change from baseline in pre-bronchodilator percent-predicted forced
      expiratory volume in 1 second at week 16. Secondary end points included change
      from baseline at week 16 in postbronchodilator percent-predicted forced
      expiratory volume in 1 second, Asthma Control Questionnaire scores, weekly
      averages of Daytime and Nighttime Asthma Diary Symptom Scores, and weekly average
      of number of puffs in a day that rescue medication was used. RESULTS: There was
      no significant difference between groups in pre-bronchodilator percent-predicted
      forced expiratory volume in 1 second at week 16 (difference in least-square means
      -0.19%; 95% confidence interval -3.01 to 2.64; P = .90). Similarly, there were no
      significant differences between groups at week 16 in changes from baseline in the
      secondary end points (P >= .30). Toreforant was generally well tolerated. No
      deaths or serious adverse events were reported at any time point. CONCLUSION:
      Toreforant, at the dose tested, failed to provide therapeutic benefit in this
      population of patients with uncontrolled, eosinophilic, persistent asthma. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT01823016.

PMID- 30102966
TI  - Resilience and immunity.
AB  - Resilience is the process that allows individuals to adapt to adverse conditions
      and recover from them. This process is favored by individual qualities that have
      been amply studied in the field of stress such as personal control, positive
      affect, optimism, and social support. Biopsychosocial studies on the individual
      qualities that promote resilience show that these factors help protect against
      the deleterious influences of stressors on physiology in general and immunity in
      particular. The reverse is also true as there is evidence that immune processes
      influence resilience. Most of the data supporting this relationship comes from
      animal studies on individual differences in the ability to resist situations of
      chronic stress. These data build on the knowledge that has accumulated on the
      influence of immune factors on brain and behavior in both animal and human
      studies. In general, resilient individuals have a different immunophenotype from
      that of stress susceptible individuals. It is possible to render susceptible
      individuals resilient and vice versa by changing their inflammatory phenotype.
      The adaptive immune phenotype also influences the ability to recover from
      inflammation-induced symptoms. The modulation of these bidirectional
      relationships between resilience and immunity by the gut microbiota opens the
      possibility to influence them by probiotics and prebiotics. However, more focused
      studies on the reciprocal relationship between resilience and immunity will be
      necessary before this can be put into practice.

PMID- 30102967
TI  - C-reactive protein and response to lurasidone in patients with bipolar
      depression.
AB  - Prior studies suggest that the inflammatory biomarker c-reactive protein (CRP)
      holds promise for predicting antidepressant response in patients with major
      depressive disorder. The objective of this study was to evaluate whether CRP
      might similarly predict antidepressant responses to lurasidone in patients with
      bipolar I depression. Serum CRP concentration was measured prior to, and
      following, 6 weeks of treatment in 485 outpatients with bipolar I depression.
      Patients were randomized to receive monotherapy with lurasidone 20-60 mg/day (N =
      161), lurasidone 80-120 mg/day (N = 162) or placebo (N = 162). CRP was assessed
      using the wide-range CRP assay (wr-CRP). The primary efficacy endpoint was change
      from baseline to week 6 in Montgomery-Asberg Depression Rating Scale (MADRS)
      score. Mixed models and statistical interaction tests were applied to investigate
      the moderating effects of pre-treatment wr-CRP on clinical endpoints. CRP was
      evaluated as a log-transformed continuous variable and by clinically-relevant cut
      points. Increasing pre-treatment wr-CRP level predicted a larger overall
      antidepressant response to lurasidone, as well as an increased response for a
      number of individual depressive symptoms. These moderating effects of pre
      treatment wr-CRP remained significant after adjustment for potential confounds
      (e.g. baseline BMI and weight change). Treatment with lurasidone did not affect
      serum concentrations of CRP compared to placebo during the study. Elevated CRP
      level prior to treatment was associated with an enhanced clinical response to
      lurasidone in patients with bipolar I depression. If confirmed in future studies,
      CRP may represent a clinically useful diagnostic and predictive biomarker
      supporting a precision medicine approach to the treatment of bipolar depression.

PMID- 30102968
TI  - The tricarboxylic acid cycle, cell wall integrity pathway, cytokinesis and
      intracellular pH homeostasis are involved in the sensitivity of Candida albicans
      cells to high levels of extracellular calcium.
AB  - Through a genetic screen we have identified 21 genes whose inactivation renders
      Candida albicans cells sensitive to high levels of extracellular calcium. These
      genes are involved in the tricarboxylic acid cycle, cell wall integrity pathway,
      cytokinesis, intracellular pH homeostasis, magnesium transport, as well as DNA
      damage response and repair processes. The calcium sensitivity due to inactivation
      of nine of these genes can be partially or completely suppressed by cyclosporine
      A, an inhibitor of calcineurin. Therefore, the calcium sensitivity of nearly a
      half of these 21 mutations is at least partially due to the activation of
      calcium/calcineurin signaling. Our work provides a basis for further
      understanding the regulation of calcium homeostasis in this important human
      fungal pathogen.

PMID- 30102969
TI  - Preoperative Statin Use Not Associated With Improved Outcomes After Ascending
      Aortic Repair.
AB  - Statins have potent pleiotropic effects that have been correlated with improved
      perioperative cardiovascular surgery outcomes. We hypothesize that statins may
      improve morbidity and mortality after ascending aortic surgery. Within a
      statewide database consisting of 19 centers a total of 1804 patients had
      ascending aortic repair with or without aortic valve replacement (2004-2016).
      Patients were stratified by preoperative statin therapy for analysis. To account
      for baseline differences, patients were propensity matched in a 1:1 fashion by
      baseline characteristics. Patient characteristics and outcomes were analyzed by
      paired analysis. Of 1804 patients undergoing ascending aortic repair, 35% took
      statins preoperatively. After matching, 386 patients in each group were well
      matched with no statistically significant baseline or operative differences.
      There was no statistically significant difference in outcomes between patients
      taking statins preoperatively and those not taking statins, including operative
      mortality (3.6% vs 3.1%, P = 0.68) and major morbidity (18.4% vs 17.1%, P =
      0.62). Postoperative atrial fibrillation (27.2% vs 28.5%, P = 0.71) and acute
      kidney injury (3.1% vs 4.2%, P = 0.41) also showed no statistically significant
      difference. Statins have no apparent clinical impact on perioperative outcomes
      after ascending aortic aneurysm repair. Considering recent evidence suggesting
      statins may increase perioperative risk of acute kidney injury, there is
      insufficient evidence to recommend starting preoperative statin before ascending
      aortic repair.

PMID- 30102970
TI  - Ninety-Day Readmissions of Bundled Valve Patients: Implications for Healthcare
      Policy.
AB  - Medicare's Bundle Payment for Care Improvement (BPCI) Model 2 groups
      reimbursement for valve surgery into 90-day episodes of care, which include
      operative costs, inpatient stay, physician fees, postacute care, and readmissions
      up to 90days postprocedure. We analyzed our BPCI patients' 90-day outcomes to
      understand the late financial risks and implications of the bundle payment system
      for valve patients. All BPCI valve patients from October 2013 (start of risk
      sharing phase) to December 2015 were included. Readmissions were categorized as
      early (<=30 days) or late (31-90 days). Data were collected from institutional
      databases as well as Medicare claims. Analysis included 376 BPCI valve patients:
      202 open and 174 transcatheter aortic valves (TAVR). TAVR patients were older
      (83.6 vs 73.8 years; P = 0.001) and had higher Society of Thoracic Surgery
      predicted risk (7.1% vs 2.8%; P = 0.001). Overall, 18.6% of patients (70/376) had
      one-or-more 90-day readmission, and total claim was on average 51% greater for
      these patients. Overall readmissions were more common among TAVR patients (22.4%
      (39/174) vs 15.3% (31/202), P = 0.052) as was late readmission. TAVR patients had
      significantly higher late readmission claims, and early readmission was
      predictive of late readmission for TAVR patients only (P = 0.04). Bundled claims
      for a 90-day episode of care are significantly increased in patients with
      readmissions. TAVR patients represent a high-risk group for late readmission,
      possibly a reflection of their chronic disease processes. Being able to identify
      patients at highest risk for 90-day readmission and the associated claims will be
      valuable as we enter into risk-bearing episodes of care agreements with Medicare.

PMID- 30102971
TI  - Engineering an in vivo EP-bifido pathway in Escherichia coli for high-yield
      acetyl-CoA generation with low CO2 emission.
AB  - The low carbon yield from native metabolic machinery produces unfavorable process
      economics during the biological conversion of substrates to desirable
      bioproducts. To obtain higher carbon yields, we constructed a carbon conservation
      pathway named EP-bifido pathway in Escherichia coli by combining Embden-Meyerhof
      Parnas Pathway, Pentose Phosphate Pathway and "bifid shunt", to generate high
      yield acetyl-CoA from glucose. 13C-Metabolic flux analysis confirmed the
      successful and appropriate employment of the EP-bifido pathway. The CO2 release
      during fermentation significantly reduced compared with the control strains. Then
      we demonstrated the in vivo effectiveness of the EP-bifido pathway using poly
      beta-hydroxybutyrate (PHB), mevalonate and fatty acids as example products. The
      engineered EP-bifido strains showed greatly improved PHB yield (from 26.0 mol% to
      63.7 mol%), fatty acid yield (from 9.17% to 14.36%), and the highest mevalonate
      yield yet reported (64.3 mol% without considering the substrates used for cell
      mass formation). The synthetic pathway can be employed in the production of
      chemicals that use acetyl-CoA as a precursor and can be extended to other
      microorganisms.

PMID- 30102972
TI  - A real time high-resolution melting PCR assay for detection and differentiation
      among sheep pox virus, goat pox virus, field and vaccine strains of lumpy skin
      disease virus.
AB  - In this paper, we report on the development of a real time high-resolution
      melting (HRM) PCR assay for detection and differentiation among sheep pox virus
      (SPPV), goat pox virus (GTPV), field isolates and vaccine strains of lumpy skin
      disease virus (LSDV) based on high-resolution melting curve analysis of their
      target PCR amplicons. A 111 bp region of LSDV010 ORF, which harbors unique
      genetic differences for each of these viral species, was selected as the PCR
      target in this study. During the validation of this assay using DNA from clinical
      isolates originated from naturally infected animals from the different geographic
      locations and reference strains, the obtained PCR amplicons demonstrated that the
      melting temperature picks were specific for each tested viral species, i.e.,
      74.56 +/- 0.04  degrees C for field LSDV, 74.95 +/- 0.08  degrees C for vaccine
      LSDV, 74.24 +/- 0.06  degrees C for SPPV and 73.61 +/- 0.04  degrees C for GTPV.
      The assessment of the assay sensitivity utilizing a LSDV field strain as a PCR
      template revealed the assay detection limit as low as 0.1 TCD50 lg/ml. Overall,
      this assay based on Rotor-Gene Q (QIAGEN) platform was shown to be reproducible
      across replicates and operators and can be recommended as an additional
      diagnostic tool to the currently available molecular assays for detection and
      differentiation of the genus Capripoxvirus species, including the differentiation
      of vaccine strains of LSDV from field isolates. The assay can be used for
      detection of these viruses in animal- and insect-derived field specimens.

PMID- 30102973
TI  - A fully automated three-step protein purification procedure for up to five
      samples using the NGC chromatography system.
AB  - The drug discovery process in the biopharmaceutical industry usually starts with
      the generation of plasmids coding for certain proteins. Due to advances in
      cloning techniques the generation of thousands of different plasmids is not a
      limiting factor anymore. The next step is the expression and evaluation of the
      proteins. In recent years significant progress has been made in the
      miniaturization of protein expression and purification. These processes have been
      adapted to robotic platforms and hundreds of proteins can be expressed and
      purified in parallel. As a consequence of miniaturization, the protein
      purification is restricted to a one-step process. In addition the amount of
      purified protein is usually in the MUg-range. This might be suitable if a
      sensitive initial screening assay is available. However, when larger amounts of
      proteins are required robotic platforms are no longer appropriate. In addition, a
      one-step purification procedure is often not sufficient to obtain pure protein
      preparations. To address this topic we have used the NGC chromatography system
      for automated purification of up to five samples using a three-step purification
      procedure. The first chromatographic step is the capture step followed by a
      desalting step. The final purification was done using size exclusion
      chromatography. This set-up reduces the overall-time needed for protein
      production, needs minimal operator invention, is easy to handle and thus
      increases the throughput.

PMID- 30102974
TI  - Protective efficacy of Shilajit enriched diet on growth performance and immune
      resistance against Aeromonas hydrophila in Oreochromis mossambicus.
AB  - We investigated the effects of dietary enriched with Shilajit in three dose
      levels: 2.0, 4.0, and 6.0 g kg-1 in the basal diet on growth rate, non-specific
      immune response, and disease resistance for 60 days in Oreochromis mossambicus
      against an opportunist pathogen, Aeromonas hydrophila. The results showed that
      the Shilajit enriched diets at 4.0 and 6.0 g kg-1 diets significantly (p < 0.05)
      enhance survival rate, weight gain (WG), protein efficiency ratio (PER), specific
      growth rate (SGR), and feed efficiency (FE), whereas it significantly decrease
      the feed conversion ratio (FCR) from weeks 1-4 when compared with control. The
      innate immune parameters, such as the phagocytic, complement, respiratory burst,
      and lysosome activities in infected fish fed with all Shilajit enriched diet were
      significantly (p < 0.05) enhances on weeks 2-4. A very low cumulative mortality,
      8.0% and 12.0% were observed in the infected fish fed with 4.0 and 6.0 g kg-1
      Shilajit enriched diets, whereas 18% mortality was found with 2 g kg-1 diet. In
      conclusion, 4.0 and 6.0 g kg-1 Shilajit enriched diets significantly increased
      the growth performance, innate immune response, and disease resistance in O.
      mossambicus against A. hydrophila infection.

PMID- 30102975
TI  - Accelerated functional losses in ageing congenital Minamata disease patients.
AB  - Severe methylmercury poisoning occurred in Minamata and neighboring communities
      in Japan during the 1950s and 1960s. A considerable number of children were born
      with conditions resembling cerebral palsy, later known as congenital Minamata
      disease. Although surviving patients are now in their 50s or 60s, few assessments
      of functional capacities in daily living have been performed. We assessed the
      changes in Activities of Daily Living (ADL) status of 11 patients over a 10-year
      period. For assessment of ADL, we applied the Barthel Index (BI) and the
      Functional Independence Measure (FIM). We obtained the patients' current and
      previous status information by interview of their caregivers or from medical
      records and then compared them using the Wilcoxon signed-rank test. Both ADL
      measures, including the status related with cognition, had significantly declined
      during the 10 years. The same was true for the overall BI score (p = 0.01).
      Similarly, all functions of the FIM scores declined (i.e., self-care, sphincter
      control, mobility, locomotion, communication, and social cognition), and for FIM
      physical and cognition subscores as well as FIM total score, the declines were
      statistically significant. The present study indicates that the ADL status of
      congenital Minamata disease patients, now in their 50s or 60s, has substantially
      declined during the last 10 years; a decline that was much steeper in comparison
      with expectation in subjects of similar ages, but in agreement with accelerated
      ageing also reported in subjects with cerebral palsy, past polio infection, or
      epilepsy. While already incapacitated due to the prenatal methylmercury
      poisoning, their accelerated ageing may suggest that patients with developmental
      neurotoxicity have less reserve capacity to compensate for normal ageing. These
      patients will need continuous and increasing medical and welfare support in the
      community.

PMID- 30102976
TI  - The genetic relationship between R. microplus and R. decoloratus ticks in South
      Africa and their population structure.
AB  - Rhipicephalus microplus and R. decoloratus are one-host ticks that preferentially
      feed on cattle. They are capable of transmitting various tick-borne pathogens
      which may be detrimental to the agricultural and livestock industry in South
      Africa. Previous studies have shown that R. microplus forms five lineages in the
      R. microplus complex, segregating into different geographical areas based on
      mitochondrial markers. This study examined the phylogenetic relationship within
      and between R. microplus and R. decoloratus using the nuclear internal
      transcribed spacer 2 (ITS2) and mitochondrial cytochrome oxidase subunit I (COI)
      genes. The results showed that the nuclear ITS2 marker is informative for
      interspecific variation but lacks the resolution for intraspecific variation.
      Analysis of the mitochondrial COI gene revealed that R. microplus ticks from
      South Africa grouped into a clade comprised of ticks from Asia and South America.
      The population structure of these two tick species was also investigated using
      novel microsatellite markers. Population structure analyses revealed that both
      the R. microplus and R. decoloratus populations presented with two genetic
      clusters. Rhipicephalus microplus ticks from the Kwa-Zulu Natal (KZN) province
      belonged to cluster 1, and those from the Eastern Cape (EC) province
      predominantly grouped into cluster 2. No observable population structure was
      noted for R. decoloratus. The overlap of genetic clusters in both species could
      be attributed to inbreeding between the regions by unrestricted movement of
      cattle across provinces. Such movement promotes tick mobility, gene flow and the
      homogenisation of tick populations.

PMID- 30102977
TI  - A new coumarin derivative plays a role in rhabdoviral clearance by interfering
      glycoprotein function during the early stage of viral infection.
AB  - Coumarin forms an elite class of naturally occurring compounds that possess
      promising antiviral therapeutic perspectives. In this study, a coumarin
      derivative 7-[6-(2-methylimidazole) hexyloxy] coumarin (D5) was designed and
      synthesized to evaluate antiviral activity on a rhabdovirus, spring viraemia of
      carp virus (SVCV). Our results demonstrated that D5 had a robust antiviral
      activity with >90% inhibitory rate of SVCV expression in the host cells. And D5
      significantly reduced viral-induced apoptosis and recovered virus-activated
      caspase-3/8/9 activities. Further data determined that SVCV could alter the
      cytoskeletal structure of EPC cells, characterized by a circumferential ring of
      microtubules and a disrupted microfilament organization, whereas cytoskeleton
      structure in D5-treated cells kept the normal morphology. Mechanistically
      speaking, D5 could interfere with SVCV replication inside or outside of cells
      through two different approaches. Before the process of virus entry into EPC
      cells, D5 had an impact on SVCV glycoprotein structure so as to disrupt viral
      binding to the cell surface or translocation to the cytosol. Another strategy for
      D5 to against SVCV was that D5 significantly suppressed SVCV-activated autophagy,
      which was beneficial for the host cells to restrict SVCV viral replication,
      accompanied by a higher phosphorylation of Akt-mTOR. In summary, our results
      revealed that D5 was effective in weakening SVCV infection and regulating SVCV
      induced undesirable conditions, and this compound provided new therapeutic
      implications for the treatment of rhabdoviruses.

PMID- 30102978
TI  - Pharmacological targeting of p38 MAP-Kinase 6 (MAP2K6) inhibits the growth of
      esophageal adenocarcinoma.
AB  - Drug repurposing with a better understanding of the underlying mechanism has
      provided new avenues to find treatment for malignancies. Esophageal
      adenocarcinoma (EAC) is a rapidly increasing cancer with a dismal 5-year survival
      rate of <15%. Lack of efficient treatment options contributes to the high
      mortality rate of EAC. To find new therapy against EAC we performed unbiased drug
      screening of an FDA-approved drug library and identified that the cardiac
      glycosides including Ouabain, Digoxin and Digitoxin efficiently inhibit the
      proliferation of EAC cell lines (OE33 and OE19) both in vitro and in vivo. RNA
      Sequencing analysis combined with RNAi screening revealed that Ouabain suppresses
      the proliferation of EAC cells through downregulation of p38 MAP-Kinase 6
      (MAP2K6, also known as MKK6). Consistently, shRNA-mediated knockdown of MKK6
      reduced the proliferation of EAC cells and tumor growth. Further analysis
      demonstrated that MKK6 inhibition leads to the reduced levels of the
      transcription factor SOX9. In line with this finding, deletion of SOX9 with
      CRISPR/Cas9 resulted in decreased proliferation of EACs in 3D organoid culture
      and reduced tumor growth. Together these findings establish a druggable axis that
      can be harnessed for therapeutic gain against EAC.

PMID- 30102979
TI  - Discussions on the hepatic well-stirred model: Re-derivation from the dispersion
      model and re-analysis of the lidocaine data.
AB  - Roberts and Rowland explained the well-stirred model as an extreme case of the
      dispersion model when the dispersion number is infinity. However, the
      inconsistency within and discrepancy between the theoretical explanation and
      experimental observations of the well-stirred model are discovered. In this
      paper, the well-stirred model is examined from both mathematical and
      physiological points of view. The well-stirred model is re-derived from the
      convection-elimination equation using the finite difference method. The well
      stirred model is a subset of the parallel-tube model when the dispersion number
      is zero and concentration gradient is ignored. The relative errors and
      sensitivities of the well-stirred and the parallel-tube models are compared using
      numerical simulations. The well-stirred model should not be used to estimate in
      vivo apparent intrinsic clearance from hepatic extraction ratio for high
      extraction ratio drugs and predicting availability is not recommended for high
      extraction ratio drugs with either the well-stirred or the parallel-tube models.
      Based on our theoretical derivation and numerical simulations, we found lidocaine
      data analysis in Pang and Rowland's 1977 paper was based on an unfair comparison
      of these two models at two different efficiency number ranges. The high
      sensitivity of the parallel-tube model at a relatively lower efficiency number
      range versus the lack of sensitivity of the well-stirred model at an extremely
      high efficiency number range leads one to believe that the well-stirred model fit
      the data of high extraction ratio drugs such as lidocaine better. However, the
      intrinsic clearance values estimated by the parallel-tube model are much more
      consistent with both in vitro data and those estimated by the dispersion model
      than those by the well-stirred model. In addition, a key assumption used in the
      data analysis that the intrinsic clearance is independent of changes in blood
      flow may not be true. Both theoretical discussions and experimental results
      indicate that apparent intrinsic clearance and intrinsic clearance could be
      affected by blood flow and protein binding. Moreover, the lidocaine data analysis
      in 1977 paper could be control condition dependent and misleading when it is
      applied to data from other drugs, such as diazepam and diclofenac. The
      distinction between the well-stirred and parallel-tube models is a result of the
      mathematical treatment of concentration gradient rather than the flow pattern or
      extent of physical mixing. The well-stirred model is not likely better than the
      parallel-tube model. One should be cautious of using the well-stirred model for
      comparing in vitro intrinsic clearance and estimated in vivo "intrinsic
      clearance" for high clearance drugs.

PMID- 30102981
TI  - Inflammation, angiogenesis and fibrogenesis are differentially modulated by
      distinct domains of the snake venom metalloproteinase jararhagin.
AB  - Jararhagin, a metalloprotease from Bothrops jararaca snake venom, is a toxin
      containing the metalloproteinase, disintegrin-like and cysteine-rich domains; it
      causes acute inflammation and damage to vascular tissue. However, the actions of
      these domains on key components of chronic inflammation have not been determined.
      Our aim was to investigate the effects of jararhagin (Jar), jararhagin-C (Jar-C)
      and o-phenantrolin-treated jararhagin (Jar-Phe), on inflammatory response, blood
      vessel formation and extracellular matrix deposition in the murine sponge model.
      The polyether-polyurethane sponge matrix was implanted into Balb/c mice and
      injected daily with Jar (400 ng), Jar-Phe (400 ng), Jar-C (200 ng) or saline
      (control). Nine days after implantation, the sponge discs were removed and
      processed. In the Jar-treated implants, some of inflammatory markers (N-acetyl
      beta-d-glucosaminidase activity, CCL2 and TNF-alpha) and TGF-beta1 levels were
      higher compared with the control group. In the Jar-C group, the inflammatory
      markers myeloperoxidase activity and CXCL1 were higher compared with the control.
      In this group, VEGF levels and collagen deposition were also higher. Jar-Phe
      treatment was able to inhibit the activity and/or production of MPO, CXCL1, CCL2
      and TGF-beta. The differential effects of these proteins in modulating the main
      components of fibrovascular tissue may be exploited in the management
      fibroproliferative diseases.

PMID- 30102980
TI  - A continuous manufacturing concept for a pharmaceutical oral suspension.
AB  - The aim of this study was to investigate the applicability of an innovative
      continuous manufacturing system for semi-solid and liquid pharmaceutical
      formulations. A commercially available pharmaceutical oral suspension was
      selected as model formulation. Premixes of the raw materials were dosed via
      peristaltic pumps to the mixing compartment, which consists of two consecutive
      mixing units. An experimental design was used to study the influence of several
      process parameters (throughput, mixing speed in mixing unit 1 and mixing speed in
      mixing unit 2) on the quality attributes of the oral suspension. The pH, density,
      active pharmaceutical ingredient (API) concentration, sedimentation after 30 days
      (expressed by the sedimentation volume) and rheological characteristic (yield
      stress) of the suspension were determined. No significant influence of the
      process parameters on the pH, density and API concentration was observed. The
      throughput and mixing speed in mixing unit 1 had a significant impact on both the
      sedimentation volume and yield stress, and were therefore critical to acquire
      physical stable suspensions. Furthermore, the yield stress measured one day after
      production was predictive for the occurrence of sedimentation in the suspensions
      after 30 days. When selecting the optimal process settings, the continuously
      manufactured suspension had a similar product quality as the original batch
      processed suspension and even possessed a higher yield stress. This study
      demonstrated that the investigated innovative continuous manufacturing technology
      is suitable for the manufacturing of a commercially available pharmaceutical
      suspension and that the product quality can be optimized by adjusting the process
      parameters.

PMID- 30102982
TI  - Crystallization and structure elucidation of GDSL esterase of Photobacterium sp.
      J15.
AB  - GDSL esterase J15 (EstJ15) is a member of Family II of lipolytic enzyme. The
      enzyme was further classified in subgroup SGNH hydrolase due to the presence of
      highly conserve motif, Ser-Gly-Asn-His in four conserved blocks I, II, III, and
      V, respectively. X-ray quality crystal of EstJ15 was obtained from optimized
      formulation containing 0.10 M ammonium sulphate, 0.15 M sodium cacodylate
      trihydrate pH 6.5, and 20% PEG 8000. The crystal structure of EstJ15 was solved
      at 1.38 A with one molecule per asymmetric unit. The structure exhibits
      alpha/beta hydrolase fold and shared low amino acid sequence identity of 23% with
      the passenger domain of the autotransporter EstA of Pseudomonas aeruginosa. The
      active site is located at the centre of the structure, formed a narrow tunnel
      that hinder long substrates to be catalysed which was proven by the protein
      ligand docking analysis. This study facilitates the understanding of high
      substrate specificity of EstJ15 and provide insights on its catalytic mechanism.

PMID- 30102983
TI  - Lignin from an integrated process consisting of liquid hot water and ethanol
      organosolv: Physicochemical and antioxidant properties.
AB  - Corncob was successively pretreated by liquid hot water (LHW) and ethanol
      organosolv (EO) in an integrated process. LHW was performed at 200  degrees C for
      30 min, and EO was performed using uncatalyzed ethanol-water solutions, according
      to a design of experiments. The effects of the most influential operational
      variables (ethanol concentration, temperature and time) on yield and chemical
      composition of the fractions were assessed. Results showed the factor with the
      greatest effect was ethanol concentration (p < 0.05), leading to a high-purity
      lignin (86.7%-93.1%) with a total phenolic content of around 25 mg GAE/g.
      Moreover, the solids recovered from the high ethanol concentration conditions
      presented the lowest lignin contents (15.4%-17.2%) with good preservation of
      cellulose (82.5%-88.6% of glucans). The lignin antioxidant capacity showed that
      all lignin samples presented radical scavenging activity (IC50 of 0.17 mg/mL and
      0.016 mg/mL on DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis(3
      ethylbenzothiazoline-6-sulphonic acid) assays, respectively) with values close to
      the commercial antioxidant BHT. Moreover, the chemical (FTIR) and thermal (DSC
      and TGA) characterization showed lignins with similar properties that were
      compared with lignin from direct ethanol organosolv process. Results showed that
      the integrated process of LHW-EO was the most effective way to obtain lignin with
      high purity and antioxidant capacity.

PMID- 30102984
TI  - Differential interaction of alpha-synuclein N-terminal segment with mitochondrial
      model membranes.
AB  - Alpha-synuclein (alpha-syn) is an intrinsically-disordered protein that has been
      associated with Parkinson's disease through its deposition in an amyloid fibril
      form within Lewy Body. Several lines of evidence suggest that the physical
      association of alpha-syn with the mitochondrial membranes may cause membrane
      damage and mitochondrial dysfunction, playing an important role in disease
      progression. Although there is strong evidence that the N-terminus part of alpha
      syn is essential for membrane affinity, cooperative formation of helical domains
      and regulation of mitochondria membrane permeability, the amino acids involve in
      this membrane binding is still controversial. Fluorescence spectroscopy, circular
      dichroism and Langmuir monolayer technique were used to elucidate this
      recognition process of mitochondrial membrane system by synthetic peptides
      derived from alpha-syn N-terminal segment. The results obtained in this work show
      that the first 15 amino acid of the alpha-syn N-terminal segment mainly
      participate in the anchoring, perturbing the membrane hydrophobic region, while
      the peptide corresponding to 16-30 residues interacts only with the phospholipid
      polar headgroup, confirming that the binding affinity of the N-terminus is
      nonuniform.

PMID- 30102985
TI  - Formation and characterization of the complex coacervates obtained between
      lactoferrin and sodium alginate.
AB  - The aim of this study was to evaluate the influence of some parameters (pH, NaCl,
      and ratio of biopolymers) on the formation of the complex coacervates of
      lactoferrin and sodium alginate. Different ratios of lactoferrin:sodium alginate
      were tested (1:1, 1:2, 1:4,1:8, 2:1, 4:1, and 8:1) at pH levels ranging from 2.0
      to 7.0 with different concentrations of NaCl (0, 50, 100, 150, and 200 mM).
      Sodium alginate has a molecular weight of 138 kDa +/- 0.07. The ratio of
      8:1(lactoferrin: sodium alginate) at a pH of 4.0 with a low salt concentration
      was the optimal condition for the formation of the complex. The thermodynamic
      parameters demonstrated that the interaction between lactoferrin and sodium
      alginate was exothermic and spontaneous with a favorable enthalpic and
      unfavorable entropic contribution during the interaction. The chemical, thermal
      and morphological characteristics of the biopolymers and the complex coacervates
      demonstrated their nature and changes due to electrostatic interactions. The
      formation of complex coacervates between lactoferrrin and sodium alginate can
      serve as an alternative to the incorporation of lipophilic functional ingredients
      sensitive to high temperatures in various food systems.

PMID- 30102986
TI  - Heterologous expression of a novel d-lactate dehydrogenase from Lactobacillus sp.
      ZX1 and its application for d-phenyllactic acid production.
AB  - d-Phenyllactic acid (d-PLA) shows great potential for biopreservative production
      owning to its anti-microbial activity. In this study, strain ZX1, which could
      inhibit the growth of other microbes was isolated and identified as Lactobacillus
      genus. Strain ZX1 could produce d-PLA with 0.16 g.L-1. Furthermore, a novel d
      lactate dehydrogenase gene was identified and expressed in Escherichia coli BL21
      (DE3) with the specific activity of 71.64 U.mg-1 protein under the optimal
      temperature and pH of 35  degrees C and 6.2. The kinetic constants for Kcat, Km,
      Vmax were 10.71 s-1, 2.356 mM and 11.27 MUM.mg-1.min-1 for phenylpyruvic acid
      (PPA), respectively. 18.21 g.L-1d-PLA from PPA with yield of 90.49% and
      productivity of 2.49 g.L-1.h-1 was obtained by the recombinant E. coli BL21
      harboring d-LDH, indicating that engineered E. coli BL21 (d-LDH) has excellent
      potential in commercial d-PLA production.

PMID- 30102987
TI  - Heat-induced amyloid-like aggregation of beta-lactoglobulin regulated by
      glycation: A comparison of five kinds of reducing saccharides.
AB  - The Maillard reaction occurs extensively in food industry and can change the
      aggregation behavior of dietary proteins. In this work, we reported the influence
      of glycation on the heat-induced amyloid-like aggregation behavior of beta
      lactoglobulin (beta-Lg). Glycation was shown to accelerate the unfolding behavior
      of beta-Lg and thereby increased fibrillation rate during initial heating
      according to 1-anilinonaphthalene-8-sulfonate and thioflavin T assays.
      Prolongation of fibrils was found to be limited by glycation derived from
      glucose, fructose and lactose, possibly due to the decrease in beta-sheet
      structure of beta-Lg based on circular dichroism spectral results and
      transmission electron microscopy images. beta-Lg incubated with maltodextrin
      appeared to associate into globular micelles. Both covalent (disulfide bond and
      crosslinking structure) and non-covalent changes (steric hindrance and hydrogen
      bonds) induced by glycation are proposed to account for these fibrillation
      kinetic and conformational changes of beta-Lg aggregates. According to these
      findings, glycation are promising methods to regulate both fibrillation kinetics
      and fibril conformation in the food industry.

PMID- 30102988
TI  - The Torsed Minimally Affected Adnexa.

PMID- 30102989
TI  - Molecular engineering strategies and methods for the expression and purification
      of IgG1-based bispecific bivalent antibodies.
AB  - In recent years, bispecific antibodies (BisAbs) have emerged as novel
      pharmaceutical candidates owing to their ability to engage two disease mediators
      simultaneously, thus providing a possible alternative therapeutic approach in
      complex diseases such as cancer and inflammation. Here we provide an overview of
      the molecular design, recombinant expression in mammalian cells and purification
      of BisAbs based on full-length IgG-scFv formats. Practical considerations and
      strategies to optimize transient expression and purification are also discussed.

PMID- 30102990
TI  - Using bioreactors to study the effects of drugs on the human microbiota.
AB  - The study of complex microbial communities has become a major research focus as
      mounting evidence suggests the pivotal role microbial communities play in host
      health and disease. Microbial communities of the gastrointestinal tract, known as
      the gut microbiota, have been implicated in aiding the host with vitamin
      biosynthesis, regulation of host energy metabolism, immune system development,
      and resistance to pathogen invasion. Conversely, disruptions of the gut
      microbiota have been linked to host morbidity, including the development of
      inflammatory diseases, metabolic disorders, increased cardiovascular risk, and
      increased risk of infectious diseases. However, studying the gut microbiota in
      humans and animals is challenging, as many microorganisms are fastidious with
      unique nutritional or environmental requirements that are often not met using
      conventional culture techniques. Bioreactors provide a unique solution to
      overcome some of the limitations of conventional culture techniques. Bioreactors
      have been used to propagate and establish complex microbial communities in vitro
      by recapitulating the physiological conditions found in the GI tract. These
      systems further our understanding of microbial physiology and facilitate our
      understanding of the impact of medications and xenobiotics on microbial
      communities. Here, we review the versatility and breadth of bioreactor systems
      that are currently available and how they are being used to study faecal and
      defined microbial communities. Bioreactors provide a unique opportunity to study
      complex microbial interactions and perturbations in vitro in a controlled
      environment without confounding biotic and abiotic variables.

PMID- 30102991
TI  - Spinal Serotonin 1A Receptor Contributes to the Analgesia of Acupoint Catgut
      Embedding by Inhibiting Phosphorylation of the N-Methyl-d-Aspartate Receptor
      GluN1 Subunit in Complete Freund's Adjuvant-Induced Inflammatory Pain in Rats.
AB  - Acupoint catgut embedding (ACE) is a widely used traditional Chinese medicine
      method to manage various diseases, including chronic inflammatory pain. We sought
      to assess the possible analgesic effects of ACE in comparison with
      electroacupuncture (EA) and to study the analgesic mechanisms of ACE in a rat
      model of inflammatory pain induced by injection of complete Freund's adjuvant
      (CFA) into the hind paw of rats. The von Frey, radiant heat, and gait analysis
      tests were performed to evaluate the analgesic effects of ACE and EA, and Western
      blot and immunohistochemistry assays were carried out to determine the molecular
      mechanisms of ACE. ACE treatments were administered every 4 days or every week
      with different acupoints (ipsilateral, contralateral, or bilateral ST36 and GB30
      acupoints). The most effective ACE strategy for attenuating the nocifensive
      response induced by CFA injection was performing ACE once a week at ipsilateral
      ST36 in combination with GB30. EA treatment every other day at ipsilateral ST36
      and GB30 showed comparable analgesic effects. ACE inhibited the increased
      activation of the GluN1 subunit of the N-methyl-d-aspartate receptor and the
      subsequent Ca2+-dependent signals (CaMKII, ERK, and CREB) that take place in
      response to CFA. The effects of ACE were similar to intrathecal injection of
      vilazodone (a serotonin 1A receptor [5-HT1AR] agonist) and were blocked by WAY
      100635 (a 5-HT1AR antagonist). In summary, we show that ACE attenuates CFA
      induced inflammatory pain in rats by activating spinal 5-HT1AR and by inhibiting
      the phosphorylation of GluN1, thus, inhibiting the activation of Ca2+-dependent
      signaling cascades. PERSPECTIVE: This article presents the novel evidence
      concerning the spinal 5-HT1AR activation-related molecular signaling of ACE
      analgesia in a rat model of CFA-induced inflammatory pain. This work may help
      clinicians to verify the effectiveness of ACE analgesia and to better understand
      the underlying mechanism.

PMID- 30102992
TI  - Effects on skin of Stichopus japonicus viscera extracts detected with saponin
      including Holothurin A: Down-regulation of melanin synthesis and up-regulation of
      neocollagenesis mediated by ERK signaling pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Stichopus japonicus (sea cucumber), edible
      traditional food in Asia, and its extracts are renowned for their wound healing,
      pain relieving, and cosmetic effects in traditional medicine. Holothurins, toxins
      isolated from sea cucumber, are thought to be active components for their
      beneficial effects. However, researchers have yet to outline specific mechanisms
      thereof. AIM OF THE STUDY: The present study was designed to evaluate the anti
      melanogenic and anti-wrinkle properties of S. japonicus viscera extracts (VF) on
      the skin via in vitro and ex vivo experiments and to assess the anti-aging
      effects of S. japonicus viscera extracts in relation to known wound healing and
      cosmetic processes. MATERIALS AND METHODS: The viscera of live S. japonicus
      specimens were freeze dried and ground into a powder. Aqueous extracts were
      subsequently prepared from the concentrated powder using a water extraction
      method. To investigate the inhibitory effects of VF on melanogenesis, mushroom
      tyrosinase activity assay and melanin assay were performed on Melan-A cells. To
      further delineate the anti-melanogenic properties of VF, western blot analysis
      for tyrosinase, TRP-1, TRP-2, MITF, and ERK was conducted. Changes in collagen
      synthesis in human dermal fibroblast (HDF) were evaluated via CCK-8 assay and
      immunocytochemistry to determine the anti-wrinkle effects of VF. Finally, anti
      aging properties were examined in a human skin equivalent ex vivo model. RESULTS:
      In Melan-A cells, VF treatment reduced melanin contents in a concentration
      dependent manner. The anti-melanogenic effects of VF appeared to be due to
      enzymatic inhibition of tyrosinase. In CCK-8 assay, VF also significantly
      increased the viability of HDFs in a concentration-dependent manner. Immunoblot
      analysis revealed phosphorylation of ERK in HDFs treated with VF. In a human skin
      equivalent ex vivo model (Neoderm(r)-ED), VF treatment at a concentration of 50
      MUg/ml enhanced collagen type IV and Ki-67 expression and downregulated MMP-9
      expression. CONCLUSION: This study demonstrated that aqueous extracts from S.
      japonicus viscera are effective whitening and anti-aging agents that stimulate
      ERK signaling to inhibit melanin synthesis and promote collagen synthesis.

PMID- 30102994
TI  - The ethanolic extract from Erythrina mulungu Benth. flowers attenuates allergic
      airway inflammation and hyperresponsiveness in a murine model of asthma.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Erythrina mulungu Benth. ("mulungu", Fabaceae) is
      a Brazilian native species with ethnopharmacological use for respiratory
      diseases. However, the effects of E. mulungu on the respiratory were never
      studied. AIMS OF THE STUDY: To evaluate the effects of an ethanolic extract from
      flowers of E. mulungu in ovalbumin (OVA)-induced asthma in mice, and to study the
      mechanisms involved. MATERIALS AND METHODS: OVA-sensitized mice were
      intraperitoneally (i.p.) treated with four doses (200, 400, 600, and 800mg/kg) of
      the E. mulungu extract or dexamethasone (DEXA, 2mg/kg) during seven consecutive
      days and simultaneously challenged with intranasal OVA. Bronchial
      hyperresponsiveness was evaluated in vivo, 24h after the last OVA challenge.
      Bronchoalveolar lavage (BAL) was collected for counting the number of total and
      differential inflammatory cells. Blood was collected for measurement of anti-OVA
      IgE levels. Levels of cytokines interleukin (IL)-4, IL-5, IL-10, IL-13, and
      interferon (INF)-gamma were measured in pulmonary homogenate by ELISA. The
      recruitment of inflammatory cells to the lung tissue was determined using
      hematoxylin and eosin staining (H&E). The extract's chromatographic profile was
      evaluated by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS).
      RESULTS: The treatment with E. mulungu extract significantly reduced bronchial
      hyperresponsiveness, significantly reduced the number of leukocytes, eosinophils,
      and lymphocytes in BAL, and significantly decreased the levels of IL-4 and IL-5,
      while increased levels of IL-13 and INF-gamma. In addition, E. mulungu
      significantly decreased the cellular inflammatory infiltration in the lung
      tissue. Erysotrine, erysotrine-N-oxide, and hypaphorine were the major
      constituents identified in the extract. CONCLUSION: Collectively, these results
      confirm the potential of E. mulungu for asthma treatment, through modulation of
      inflammatory response, supporting its ethnopharmacological use for respiratory
      diseases.

PMID- 30102993
TI  - Bioassay-guided isolation and UHPLC-DAD-ESI-MS/MS quantification of potential
      anti-inflammatory phenolic compounds from flowers of Inula montana L.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Flowers of Inula montana L. (Asteraceae),
      commonly known as "Arnica de Provence", are used in the traditional medicine of
      Provence in France with the same indication as Arnica montana, for the relief of
      bruises, as an anti-inflammatory agent. AIMS OF THE STUDY: The aim of our study
      is to evaluate its anti-inflammatory properties and to justify its traditional
      uses. Its potential valorization is evaluated in order to propose Inula montana
      as an alternative to Arnica montana. MATERIALS AND METHODS: Bio-guided
      fractionation of ethanolic extract allowed the isolation of compounds responsible
      of the inhibition of NO production. The fractionation was realized using
      chromatographic techniques and structure elucidation was conducted by ESI-MS and
      NMR spectral data. Anti-inflammatory effect of ethanolic extract, different
      fractions and isolated pure compounds was studied in vitro on immortalized mouse
      macrophages RAW 264.7. An analytical UHPLC-DAD-ESI-MS/MS method was developed for
      the identification of these compounds in the herbal drug. This UHPLC-DAD method
      was validated and was used to compare the phenolic profile and content in plant
      material from the two collection sites: Bonnieux and Merindol. RESULTS: Eleven
      compounds were identified by UHPLC-MS. Chlorogenic acid (1), Luteolin (2),
      Nepetin (3), 3,5-O-Dicaffeoylquinic acid (4), 1,5-O-Dicaffeoylquinic acid (5),
      Nepitrin (6), Hispiduloside (7) and Jaceosid (8) were isolated and identified by
      NMR. Compounds 9, 10 and 11 were confirmed to be 6-Hydroxykaempferol 3,7-dimethyl
      ether, Hispidulin and Chrysosplenol C, respectively by comparing retention times
      and MS/MS data with those of the authentic substances. Six compounds: 1 and 4-8
      are reported for the first time in Inula montana L. Compounds 2-8 showed
      promising anti-inflammatory activity with the release of NO with IC50 value < 7
      uM. The UHPLC-DAD method of quantification of three major bioactive compounds (1,
      3 and 5) was validated. CONCLUSION: Flowers extracts and isolated compounds
      present promising anti-inflammatory activity which provides a scientific basis
      for the traditional use of Inula montana and may be proposed in the same
      indications as Arnica montana. The developed and validated simple, accurate and
      rapid UHPLC method can be used for the quality control of the herbal drug.

PMID- 30102995
TI  - Shared biological pathways for frailty and cognitive impairment: A systematic
      review.

PMID- 30102996
TI  - The effects of physical exercise on executive function in community-dwelling
      older adults living with Alzheimer's-type dementia: A systematic review.
AB  - Executive function deficit is an indicator of Alzheimer's-type dementia and
      manifests as disruptions of attentional control, memory, cognitive flexibility,
      planning, and reasoning, among other cognitive problems. Physical exercise is
      suggested to have a protective effect on global cognition with aging. However,
      whether it influences executive function in people living with Alzheimer's-type
      dementia specifically is unknown. The current systematic review examined the
      efficacy of physical exercise on executive function performance in community
      dwelling older adults living with Alzheimer's-type dementia. An electronic search
      of databases retrieved randomized and non-randomized controlled trials of
      community-dwelling older adults diagnosed with Alzheimer's-type dementia who
      completed a physical exercise intervention and who were assessed using an
      executive function outcome measure. Methodological quality of six studies meeting
      the inclusion criteria published between 2009 and 2016 was scored independently
      by two raters using the Physiotherapy Evidence Database and a Cochrane informed
      domain-based assessment of risk of bias. Trends toward improvement in executive
      function scores were seen across all six studies, and significant improvement was
      seen in four of the eligible studies. Future studies should explore the benefits
      of the American College of Sports Medicine recommended 150 min of physical
      exercise per week with select measures of executive function.

PMID- 30102998
TI  - A three-dimensional digital neurological atlas of the mustached bat (Pteronotus
      parnellii).
AB  - Substantial knowledge of auditory processing within mammalian nervous systems
      emerged from neurophysiological studies of the mustached bat (Pteronotus
      parnellii). This highly social and vocal species retrieves precise information
      about the velocity and range of its targets through echolocation. Such high
      acoustic processing demands were likely the evolutionary pressures driving the
      over-development at peripheral (cochlea), metencephalic (cochlear nucleus),
      mesencephalic (inferior colliculus), diencephalic (medial geniculate body of the
      thalamus), and telencephalic (auditory cortex) auditory processing levels in this
      species. Auditory researchers stand to benefit from a three dimensional brain
      atlas of this species, due to its considerable contribution to auditory
      neuroscience. Our MRI-based atlas was generated from 2 sets of image data of an
      ex-vivo male mustached bat's brain: a detailed 3D-T2-weighted-RARE scan [(59 * 63
      x 85) MUm3] and track density images based on super resolution diffusion tensor
      images [(78) MUm3] reconstructed from a set of low resolution diffusion weighted
      images using Super-Resolution-Reconstruction (SRR). By surface-rendering these
      delineations and extrapolating from cortical landmarks and data from previous
      studies, we generated overlays that estimate the locations of classic functional
      subregions within mustached bat auditory cortex. This atlas is freely available
      from our website and can simplify future electrophysiological, microinjection,
      and neuroimaging studies in this and related species.

PMID- 30102997
TI  - Increasing beta-amyloid deposition in cognitively healthy aging predicts
      nonlinear change in BOLD modulation to difficulty.
AB  - Recent evidence indicates that the relationship between increased beta-amyloid
      (Abeta) deposition and functional task-activation can be characterized by a non
      linear trajectory of change in functional activation (Foster et al., 2017),
      explaining mixed results in prior literature showing both increases and decreases
      in activation as a function of beta-amyloid burden in cognitively normal adults.
      Here we sought to replicate this nonlinear effect in the same sample using a
      different functional paradigm to test the generalizability of this phenomenon.
      Participants (N = 68 healthy adults aged 49-94) underwent fMRI (0-, 2-, 3-, 4
      back working memory task; WM) and 18F-Florbetapir PET scanning. A parametric WM
      load contrast was used as the dependent variable in a model with age, mean
      cortical Abeta, and Abeta2 as predictors. Results revealed that nonlinear amyloid
      (Abeta2) was a significant negative predictor of modulation of activation to WM
      load in two large inferior clusters: bilateral subcortical nuclei and bilateral
      lateral cerebellum. Individuals with slightly elevated Abeta burden evidenced
      greater modulation as compared to individuals with little or no Abeta burden,
      whereas individuals with the greatest Abeta burden evidenced lesser modulation as
      compared to individuals with slightly elevated Abeta. Increased modulation to WM
      load predicted better task accuracy and executive function measured outside the
      scanner. The current study provides further evidence for a dose-response,
      nonlinear relationship between increasing Abeta burden and alteration in brain
      activation in cognitively healthy adults, extending the existing evidence to
      dynamic range of activation to task difficulty, and reconciling seemingly
      discrepant effects of amyloid on brain function.

PMID- 30102999
TI  - Pathophysiology of levodopa-induced dyskinesia: Insights from multimodal imaging
      and immunohistochemistry in non-human primates.
AB  - BACKGROUND: Dopaminergic and serotonergic degenerations alter pharmacological
      neurotransmission and structural markers in Parkinson's disease (PD). Alteration
      of diffusion measures in key brain regions depict MPTP/MDMA lesions in the monkey
      model of PD. Whether dopatherapy impacts such diffusion measures remains an open
      question. OBJECTIVES: The aim of this study was to investigate the consequences
      of l-DOPA treatment on diffusion alterations, PET imaging and immunohistochemical
      markers in MPTP/MDMA-intoxicated monkeys. METHODS: We acquired PET imaging and
      measures of mean diffusivity and fractional anisotropy longitudinally and
      correlated them with behavior and post-mortem fiber quantification. RESULTS:
      Severity of l-DOPA-induced dyskinesia was correlated to serotonin transporter
      radioligand binding increases in the ventral striatum and the anterior cingulate
      cortex and decreases of mean diffusivity in the ventral striatum. After lesion of
      serotonergic fibers by MDMA and the second l-DOPA period, diffusion measures were
      no more altered while the serotonergic binding still increased in all regions of
      interest, despite abolition of dyskinesia. Interestingly, in the anterior
      cingulate cortex, the SERT radioligand binding was negatively correlated to the
      number of SERT fibers. CONCLUSION: These results show that the increase of SERT
      radioligand binding is not systematically paralleled by an increase of SERT
      fibers and does not always reflect the presence of LID. More specifically, our
      study suggest that SERT increase may be underpinned by an increased density of
      serotonergic fibers after MPTP and the first l-DOPA period, and by an elevation
      of SERT itself after MDMA and the second l-DOPA period. This highlights that DTI
      is complementary to PET imaging to decipher pathophysiological mechanisms
      underlying l-DOPA-induced dyskinesia in a non-human primate model of PD.

PMID- 30103000
TI  - From stroke to neurodegenerative diseases: The multi-target neuroprotective
      effects of 3-n-butylphthalide and its derivatives.
AB  - Discovering effective agents to slow or stop neurodegeneration is a challenging
      task. Over decades, only a few drugs were approved by Food and Drug
      Administration (FDA) and most ended in failure. The lessons learned have switched
      the strategy of drug discovery from designing highly selective ligands to a
      network pharmacology approach. This enables many natural products like
      butylphthalide (NBP) once again to be regarded as a valuable source of leads for
      drug discovery. In this review, we first start with the neuroprotective effects
      of NBPs on acute ischemic stroke, and later spread to their applications in major
      neurodegenerative diseases. The underlying mechanisms are also discussed in order
      to provide a direction for further study. Hopefully, this review could bring some
      new insights for drug development in this struggling field.

PMID- 30103001
TI  - Fraxinellone has anticancer activity in vivo by inhibiting programmed cell death
      ligand 1 expression by reducing hypoxia-inducible factor-1alpha and STAT3.
AB  - Dictamnus dasycarpus is a traditional Chinese medicine thathas been commonly used
      in the treatment of cancer. Fraxinellone is a natural product isolated from the
      D. dasycarpus plant, which has been shown to exhibit neuroprotective and anti
      inflammatory activities. However, whether fraxinellone exerts anticancer effects
      and the mechanisms by which it may inhibit tumor growth remain unknown. Here, we
      found that fraxinellone, in a dose-dependented manner, inhibited the expression
      of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in
      tumorigenesis. It was subsequently shown that fraxinellone reduced HIF-1alpha
      protein synthesis via the mTOR/p70S6K/eIF4E and MAPK pathways. It also inhibited
      activation of STAT3 via the JAK1, JAK2, and Src pathways. Immunoprecipitation and
      western blotting assays showed that fraxinellone inhibited PD-L1 expression by
      reducing STAT3 and HIF-1alpha cooperatively. Flow cytometry, colony formation,
      and EdU incorporation assays demonstrated that fraxinellone inhibited cell
      proliferation through suppression of PD-L1. Tube formation, migration, and
      invasion assays showed that fraxinellone inhibits angiogenesis by suppressing PD
      L1. In vivo studies further supported anticancer role for fraxinellone,
      demonstrating that fraxinellone treatment inhibited the growth of tumor
      xenografts. We concluded that fraxinellone inhibits PD-L1 expression by
      downregulating the STAT3 and HIF-1alpha signaling pathways, subsequently
      inhibiting proliferation and angiogenesis in cancer cells. These studies reveal
      previously unknown characteristics of fraxinellone and provide new perspectives
      into the mechanism of cancer inhibition of the compound.

PMID- 30103002
TI  - Targeting molecular pathways in cancer stem cells by natural bioactive compounds.
AB  - Cancer Stem Cells (CSCs) or Tumor-Initiating Cells (TICs) are a small sub
      population of cells within the tumor, able to give chemio- and radio-resistance
      and cause the onset of metastasis and the presence of relapses; for these
      reasons, they are recently becoming a potential target for anticancer therapy.
      One of the main characteristics of these cells is the self-renewal through the
      capability of modulating different molecular signalling pathways, including
      Wnt/beta-Catenin, Sonic Hedgehog and Notch pathways. Natural bioactive compounds
      such as resveratrol, epigallocatechin, curcumin, quercetin, ellagic acid,
      anthocyanins and other compounds and extracts can have a direct or indirect
      effect on these molecular pathways, decreasing the pathological activities of
      CSCs. This review aims to report and summarize the in vitro and in vivo studies
      about the preventive, therapeutic and chemosensitizing effects of these natural
      bioactive compounds on CSCs deriving from different types of tumors.

PMID- 30103003
TI  - Comparative incidence and excess risk of acute kidney injury in hospitalised
      patients receiving vancomycin and piperacillin/tazobactam in combination or as
      monotherapy.
AB  - Combination therapy with vancomycin and piperacillin/tazobactam (TZP) has been
      associated with increased risk of acute kidney injury (AKI) compared with
      monotherapy with either agent. This retrospective, matched cohort study was
      conducted to assess the comparative incidence of AKI due to combination therapy
      in patients receiving vancomycin and TZP in combination or as monotherapy.
      Patients aged >=18 years admitted to Albany Medical Center (Albany, NY) between
      September 2013 and August 2014 who had received therapy for at least two
      consecutive days were included. Patients who were pregnant, neutropenic, had AKI
      on admission or with cystic fibrosis were excluded. Patients were matched on
      baseline risk of AKI. The main outcome of interest was AKI, defined as an
      increase in serum creatinine of >=0.3 mg/L or >=50% within 48 h. Secondary
      outcomes evaluated were length of hospital and ICU stay and inpatient mortality
      associated with AKI. The risk of AKI was 7.0%, 8.5% and 26.8% in the vancomycin
      monotherapy, TZP monotherapy and combination groups, respectively (P < 0.001). In
      the multivariate analysis, combination therapy was independently associated with
      an increased odds of AKI (adjusted odds ratio = 4.406, 95% confidence interval
      1.472-13.188) compared with vancomycin monotherapy. The excess risk of
      combination therapy was 11.3%. In this matched cohort study, there was an
      increased incidence of AKI in patients receiving vancomycin and TZP combination
      therapy. Further research is needed to determine the individual strategies to
      best prevent inpatient AKI in patients receiving this combination therapy.

PMID- 30103004
TI  - Development of colistin dependence in non-baumannii Acinetobacter species.

PMID- 30103005
TI  - High prevalence of triazole resistance in clinical Aspergillus fumigatus isolates
      in a specialist cardiothoracic centre.
AB  - OBJECTIVES: To evaluate the prevalence of triazole-resistant Aspergillus
      fumigatus and common molecular cyp51A polymorphisms amongst clinical isolates in
      a specialised cardiothoracic centre in London, UK. METHODS: All A. fumigatus
      isolates were prospectively analysed from April 2014 to March 2016. Isolates were
      screened with a four-well VIPcheckTM plate to assess triazole susceptibility.
      Resistance was confirmed with a standard microbroth dilution method according to
      European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines.
      Triazole-resistant A. fumigatus isolates were subjected to a mixed-format real
      time polymerase chain reaction (RT-PCR) assay (AsperGenius(r)) to detect common
      cyp51A alterations. RESULTS: We identified 167 clinical A. fumigatus isolates
      from 135 patients. Resistance to at least one azole antifungal drug was confirmed
      in 22/167 (13.2%) of isolates from 18/135 (13.3%) patients, including 12/74
      (16.2%) patients with cystic fibrosis (CF). The highest detection rate of azole
      resistant A. fumigatus was among the 11- to 20-y age group. All triazole
      resistant isolates (n = 22) were resistant to itraconazole, 18 showed cross
      resistance to posaconazole and 10 displayed reduced susceptibility to
      voriconazole. No pan-azole-resistant A. fumigatus was identified. TR34/L98H was
      identified in 6/22 (27.3%) of azole-resistant isolates and detectable in 5/12
      (42%) patients with CF. CONCLUSIONS: In our specialist cardiothoracic centre, the
      prevalence of triazole-resistant A. fumigatus is alarmingly high (13.2%). The
      majority of azole-resistant isolates were from patients with CF. We found a
      higher prevalence of the environmentally driven mutation TR34/L98H in our A.
      fumigatus isolates than in published UK data from other specialist respiratory
      centres, which may reflect differing patient populations managed at these
      institutions.

PMID- 30103006
TI  - Prognostic significance of beta-catenin expression in patients with ovarian
      cancer: A meta-analysis.
AB  - AIM: The purpose of this study was to evaluate the impact of beta-catenin
      immunohistochemical expression on the prognostic of ovarian cancer (OC) for that
      beta-catenin could be responsible for the development and progress of OC.
      METHODS: We searched various databases to identify eligible studies, and Review
      Managers 5.2 software was fulfilled in the meta-analysis. RESULTS: A total of 11
      studies were defined and composed in 1858 cases. beta-catenin expression was
      significantly correlated with poor overall survival (OS) in OC patients (HR:
      2.48, 95% CI: 1.38-4.47, P = 0.003), and showed a significant degree of
      heterogeneity (I2 = 83%, P < 0.00001). Subgroup analysis indicated that
      accumulation in the nucleus and/or cytoplasm, rather than membrane, considerably
      influences the survival of OC patients independently. CONCLUSION: Nucleus and/or
      cytoplasma of beta-catenin expression might be associated with tumor progression
      and could be a possible potential predictive factor of poor prognosis in OC
      patients.

PMID- 30103007
TI  - Identification of novel and conserved microRNA and their expression in the gray
      mouse lemur, Microcebus murinus, a primate capable of daily torpor.
AB  - MicroRNA (miRNA) are endogenous small noncoding RNA gene products, on average 22
      nt long, that play important regulatory roles in mediating gene expression by
      binding to and targeting mRNAs for degradation or translational repression. In
      this paper we identify both novel and conserved miRNA sequences present in the
      genome of the gray mouse lemur, Microcebus marinus. In total, 122 conserved and
      44 novel miRNA were identified with high confidence from the lemur genome
      (Mmur_2.0) and were used for expression analysis. All conserved and novel miRNA
      were subjected to relative quantification by RT-qPCR in liver samples from
      control and torpid lemurs. A total of 26 miRNA (16 conserved and 10 novel) showed
      increased levels during primate torpor, whereas 31 (30 conserved and 1 novel)
      decreased. Additional in silico mapping of the predicted mRNA targets of torpor
      responsive mature miRNA suggested that miRNA that increased during torpor were
      collectively involved in cell development and survival pathways, while miRNA that
      decreased were enriched in targeting immune function. Overall, the study suggests
      new regulatory mechanisms of primate torpor via miRNA action.

PMID- 30103008
TI  - Activation of p53 by costunolide blocks glutaminolysis and inhibits proliferation
      in human colorectal cancer cells.
AB  - Colorectal cancer is a leading cause of cancer-related death. Glutaminolysis has
      been suggested as a therapeutic target for cancer. Costunolide is a natural
      sesquiterpene lactone showing potent antitumor activity. Our studies were aimed
      at evaluating how costunolide affected glutaminolysis leading to proliferation
      inhibition in human colorectal cancer cells. Costunolide suppressed viability and
      proliferation of HCT116 cells concentration-dependently, but did not apparently
      affect human intestinal epithelial cells. Costunolide at 20 MUM reduced viability
      and proliferation of HCT116 cells time-dependently. Costunolide also repressed
      phosphorylation of mTOR and its downstream kinases p70S6K and 4E-BP1.
      Examinations of glutaminolysis metabolites showed that costunolide increased
      intracellular glutamine levels, but decreased intracellular levels of glutamate,
      alpha-ketoglutarate (alpha-KG), and ATP in HCT116 cells, suggesting costunolide
      blockade of glutaminolysis. Furthermore, costunolide inhibited promoter activity
      of glutaminase 1 (GLS1), the first rate-limiting enzyme in glutaminolysis, and
      reduced mRNA and protein expression of GLS1 in HCT116 cells, The GLS1 inhibitor
      BPTES, similar to costunolide, significantly reduced intracellular levels of
      alpha-KG and ATP and inhibited proliferation in HCT116 cells. Finally,
      costunolide increased phosphorylation and nuclear translocation of p53 in HCT116
      cells. Both p53 inhibitor pifithrin-alpha and p53 siRNA significantly rescued
      costunolide suppression of GLS1 promoter activity and expression in HCT116 cells.
      These data in aggregate suggested that activation of p53 was required for
      costunolide inhibition of GLS1 resulting in blockade of glutaminolysis and
      inhibition of proliferation in colorectal cancer cells, which was a novel
      mechanism underlying the antitumor activity of costunolide against colorectal
      cancer.

PMID- 30103009
TI  - SCARB1 rs5888 gene polymorphisms in coronary heart disease: A systematic review
      and a meta-analysis.
AB  - BACKGROUND: Studies have suggested that high-density lipoprotein (HDL) stimulates
      scavenger receptor class B type 1 (SR-B1) to promote hepatic uptake of
      cholesterol. SR-B1 is encoded by scavenger receptor class B member 1 (SCARB1)
      gene in human. A rare mutation in SCARB1 gene has been associated with coronary
      heart disease (CHD). A polymorphism rs5888 of SCARB1 gene has been linked to CHD
      risk in humans. OBJECTIVES: The objective was to investigate the relationship
      between the SCARB1 gene polymorphism rs5888 and risk of CHD. METHODS: We searched
      databases of case-control studies and cohort studies on rs5888 polymorphism of
      SCARB1 gene and risk of CHD. Two reviewers independently screened literature,
      extracted data, and estimated potential bias of included studies. The quality of
      the studies was evaluated by recommendation of Newcastle-Ottawa Scale (NOS). Meta
      analysis was performed with Stata 12.0 software. RESULTS: Seven studies including
      6360 subjects (cases: 2456, controls: 3904) were included in the final data
      combination. Meta-analysis showed T allele had a lower risk of CHD as compared to
      C allele in allele model (T vs. C: OR = 0.87, 95% CI: 0.70 to 1.09, P = 0.229).
      Moreover, we found that T allele or TT/TC had a lower risk of CHD as compared to
      C/CC in male in allele model (T vs. C: OR = 0.79, 95% CI: 0.61 to 1.01). However,
      no significant association was observed in women in all allele models.
      CONCLUSIONS: Our findings suggested that polymorphism rs5888 had negative
      association with CHD, especially in male. However, the conclusion needs further
      verification with high quality studies with larger sample size and rigorous
      designs.

PMID- 30103010
TI  - Integrated analysis of mRNA and miRNA expression profiles reveals muscle growth
      differences between adult female and male Chinese concave-eared frogs (Odorrana
      tormota).
AB  - The Chinese concave-eared torrent frog (Odorrana tormota) is the first known non
      mammalian vertebrate that can communicate using ultrasound. In this species,
      females are approximately four times as large as males, in which the female
      growth rate is obviously higher than that of male. Until now, the molecular
      mechanisms underlying muscle growth development differences between male and
      female frogs have not been reported. Here, we integrated mRNA and miRNA
      expression profiles to reveal growth differences in the hindlimb muscles of 2
      year-old frogs. Among 569 differentially expressed genes (DEGs), 69 were
      associated with muscle growth and regeneration. Fifty-one up-regulated genes in
      females were potentially involved in promoting muscle growth and regeneration,
      whereas 18 up-regulated genes in males may lead to muscle growth inhibition and
      fast-twitch muscle fiber contraction. 244 DEGs were enriched in mTOR and other
      protein synthesis signaling pathways, and protein degradation pathways, including
      lysosomal protease, calpain, caspase, and ubiquitin-proteasome system pathways.
      It may interpret why female muscles grow faster than males. Based on expression
      differences of genes involved in glycolysis and oxidative metabolism, we
      speculated that the proportion of slow muscle fiber was higher and that of fast
      muscle fiber was lower in female compared with male muscle. Additionally, 767
      miRNAs were identified, including 217 new miRNAs, and 6248 miRNA-negatively
      regulated mRNAs were predicted. The miRNA target genes were enriched in pathways
      related to muscle growth, protein synthesis, and degradation. Thus, in addition
      to the identified mRNA differential expressions, miRNAs may play other important
      roles in the differential regulation of hindlimb muscle growth between female and
      male O. tormota.

PMID- 30103011
TI  - Combining mouse embryonic stem cells and zebrafish embryos to evaluate
      developmental toxicity of chemical exposure.
AB  - The assays in this study utilize mouse embryonic stem cells (mESCs) and zebrafish
      embryos to evaluate the potential developmental toxicity of industrial and
      pharmaceutical chemicals. A set of eleven chemicals of known mammalian in vivo
      teratogenicity were tested in the assays and correlations to mammalian data.
      Using mESCs, proliferation, differentiation, and cytotoxicity of the chemicals
      were measured. In zebrafish embryos, lethality and the lowest effect level
      concentrations for morphological malformations were determined. Clustering of the
      assays based on frequency of affected assays resulted in a ranking of the test
      compounds that correlated to in vivo rodent data (R = 0.88, P < 0.001). We
      conclude that the combination of ESC- and zebrafish-based assays provides a
      valuable platform for the prioritization of pharmaceutical and industrial
      chemicals for further testing of developmental toxicity in rodents.

PMID- 30103012
TI  - Maternal supplementation with corn oil associated or not with di-n-butyl
      phthalate increases circulating estradiol levels of gerbil offspring and impairs
      sperm reserve.
AB  - This study evaluated the consequences of gestational exposure to di-n-butyl
      phthalate (DBP) for testicular steroidogenesis and sperm parameters of the adult
      gerbil and the interference of corn oil (co), a vehicle widely used for
      administration of liposoluble agents, on DBP effects. Pregnant gerbils received
      no treatment or were treated from gestational day 8 to 23 via gavage with 0.1
      mL/day of co only or containing DBP (100 mg/kg/day). Maternal co intake enhanced
      serum estradiol levels and testicular content of ERalpha, and reduced sperm
      reserve of adult offspring. Gestational DBP exposure caused dyslipidemia,
      increased serum and intratesticular estradiol levels and reduced sperm reserve
      and motility. Thus, maternal co supplementation alters circulating estradiol and
      impairs sperm quantity and quality of offspring. Gestational DBP exposure alters
      lipid metabolism and testicular steroidogenesis and worsens the negative effects
      of co on the sperm reserve and motility of gerbil. Therefore, co interferes with
      the reproductive response to DBP.

PMID- 30103014
TI  - Draft genome sequence of an NDM-5, CTX-M-15 and OXA-1 co-producing Escherichia
      coli ST167 clinical strain isolated from a urine sample.
AB  - OBJECTIVES: Escherichia coli is the leading cause of urinary tract infections
      worldwide. Carbapenemase-producing clinical isolates leave few therapeutic
      options. Here we report the draft genome sequence of an NDM-5, CTX-M-15, and OXA
      1 co-producing E. coli sequence type 167 (ST167) multidrug-resistant clinical
      strain (ECWJ1) isolated from a urine sample of a hospitalised male patient
      diagnosed with intracranial injury from a road traffic accident. METHODS: The
      genome of E. coli ECWJ1 was sequenced using an Illumina HiSeqTM 4000 platform.
      The generated sequence reads were assembled using CLC Genomics Workbench. The
      draft genome was annotated using the NCBI Prokaryotic Genome Annotation Pipeline
      (PGAP) server, and further bioinformatics analysis was performed. RESULTS:
      Escherichia coli ECWJ1 belongs to ST167. The total genome length of the isolate
      is 4992753bp, with 4890 protein-coding sequences. The presence of blaNDM-5,
      blaCTX-M-15 and blaOXA-1 genes was detected in addition to other antimicrobial
      resistance genes conferring resistance to aminoglycosides, fluoroquinolones,
      sulphonamides, trimethoprim and tetracyclines. Antimicrobial susceptibility
      testing revealed, that besides tigecycline and colistin, this isolate is
      resistant to all antimicrobials tested. CONCLUSIONS: To our knowledge, this is
      the first report of an E. coli ST167 strain co-producing NDM-5, CTX-M-15 and OXA
      1 isolated from urine sample in China. It may help us to understand the genomic
      features, molecular characteristics and resistance gene diversity of this
      bacterial pathogen. The genome sequence of E. coli ECWJ1 can be used as a
      reference sequence for comparative analysis of NDM-5-producing E. coli, aiming to
      reveal the mechanism of NDM-5 dissemination in this pathogen.

PMID- 30103013
TI  - Potential hazards of bisphenol A exposure to semen quality and sperm DNA
      integrity among infertile men.
AB  - Bisphenol A (BPA) is an endocrine disruptor that is widely produced as a by
      product in the plastics industry. The aim of the current study was to identify
      any association between urinary BPA levels and infertility related factors in
      patients who presented to the andrology clinic of a university hospital in Upper
      Egypt. In this case-control study, urinary BPA levels in 50 infertile patients
      and 50 matched controls were measured by high-performance liquid chromatography.
      Semen quality (sperm concentration, morphology, and motility) and oxidative
      stress (total antioxidant activity and malondialdehyde levels) were determined
      along with sperm DNA damage via alkaline comet assays. BPA concentrations were
      similarly high in urine samples from all infertile patients and fertile controls,
      with median values of 24.2 MUg/l and 20.9 MUg/l, respectively. Total BPA levels
      were negatively associated with semen quality and antioxidant levels, and
      positively correlated with DNA damage, especially with multiple semen profile
      defects, alongside seminal-plasma lipid peroxidation.

PMID- 30103015
TI  - Evaluation of animal feeds for the presence of three important antibiotic classes
      in Bhutan.
AB  - OBJECTIVES: An alarming rate of emergence of antimicrobial resistance (AMR)
      globally has urged Bhutan to take firm steps towards antibiotic stewardship
      through rational use in humans, animals and agriculture. This study aimed to
      investigate the use of three important antibiotic classes in animal feeds in
      Bhutan. METHODS: Thirteen samples were selected randomly from a pool of feed
      samples submitted by bidders for Annual Animal Feed Tender (fiscal year 2015
      2016) of the Department of Livestock. The 13 samples were tested for nitrofurans
      and their metabolites, tetracyclines and sulphonamides. The objectives of the
      study were to evaluate the feed samples for the presence of three antibiotic
      classes and, if present, to understand the level of presence (mg/kg) in terms of
      AMR emergence and spread in a Bhutanese context. RESULTS: Two feed samples,
      belonging to Indian Feed Agents, tested positive for oxytetracycline at levels of
      0.072mg/kg and 0.037mg/kg, respectively. Compared with the Feed Additive
      Compendium recommended dose (10-50g/ton) of oxytetracycline for poultry, the
      levels found in these two feeds were low. Samples testing positive for
      antibiotics were rejected in the bidding procedure as being medicated at
      prophylactic levels and could be the cause of emergence and spread of AMR in the
      country. CONCLUSION: Although the samples containing antibiotics were rejected by
      the Department of Livestock for use in government farms, some farmers may still
      use medicated feeds. Therefore, more screening needs to be conducted to further
      confirm and to prevent antibiotic abuse in animal feed in Bhutan.

PMID- 30103016
TI  - Hematopoietic Cell Transplantation for Acute Panmyelosis with Myelofibrosis: A
      Retrospective Study in Japan.
AB  - Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid
      leukemia characterized by acute onset of cytopenias and bone marrow fibrosis in
      the absence of splenomegaly. Because the prognosis of APMF is extremely poor even
      after chemotherapy, hematopoietic cell transplantation (HCT) has been used to
      treat APMF. However, the outcome after HCT for APMF remains unclear. To evaluate
      the outcomes and prognostic factors after HCT as a therapeutic modality for APMF,
      we retrospectively analyzed the Japanese registration data of 40 APMF patients
      who received allogeneic and syngeneic HCT between 2005 and 2015. The median age
      at HCT was 53.5years (range, 16 to 70). The disease status at HCT was first
      complete remission (CR1) in 13 patients (33%). The probability of overall
      survival and the cumulative incidence of relapse at 3years were 24% and 59%,
      respectively. Univariate analysis identified that female sex and disease status
      CR1 at the time of HCT were significantly associated with higher overall
      survival. Although APMF patients have a poor long-term prognosis even after
      syngeneic and allogeneic HCT, these data suggested that allogeneic HCT offered a
      curative option for APMF.

PMID- 30103017
TI  - Vascular Structure and Function in Cancer Survivors after Hematopoietic Stem Cell
      Transplantation.
AB  - This study examined the effects of hematopoietic cell transplantation (HCT) and
      associated preparative regimens on vascular structure and function. Measures of
      carotid artery stiffness and brachial artery endothelial-dependent dilation were
      obtained in patients who had survived >= 2 years after HCT for hematologic
      malignancy and were diagnosed at <=21 years. HCT survivors (n = 108) were
      examined: 66 received total body irradiation (TBI) alone or with a low-dose
      cranial radiation boost (TBI+/-LD-CRT), 19 received TBI plus high-dose cranial
      radiation (TBI+HD-CRT), and 23 received a chemotherapy-only preparative regimen
      (CHEMO). Siblings (n = 83) were invited to participate as control subjects.
      Although endothelial-dependent dilation did not differ between siblings and HCT
      survivors, carotid cross-sectional compliance, cross-sectional distensibility,
      diameter compliance, and diameter distensibility were greater in siblings than
      HCT survivors. Comparing the HCT preparative regimens, carotid cross-sectional
      compliance, cross-sectional distensibility, diameter compliance, diameter
      distensibility, and incremental elastic modulus were significantly lower in the
      TBI+HD-CRT group compared with siblings or with TBI+/-LD-CRT and CHEMO treatment
      groups. Cross-sectional distensibility and diameter compliance were significantly
      lower in the TBI+/-LD-CRT group compared with siblings. TBI+/-LD-CRT and CHEMO
      groups did not differ from each other in these vascular measures. HCT preparative
      regimens containing TBI+HD-CRT resulted in greater arterial decrements,
      indicating increased risk for cardiovascular disease.

PMID- 30103018
TI  - Graft-versus-Host Disease-Free, Relapse-Free Survival after Allogeneic Stem Cell
      Transplantation for Myelodysplastic Syndrome.
AB  - Graft-versus-host disease-free, relapse-free survival (GRFS) is a composite
      endpoint that measures survival free of relapse or significant morbidity after
      allogeneic hematopoietic stem cell transplantation (HSCT). Consecutive adult
      patients (N = 324) who received HSCT with fludarabine and busulfan-based
      conditioning for myelodysplastic syndrome (MDS) or secondary acute myeloid
      leukemia evolved from MDS were retrospectively analyzed. One-year and 3-year GRFS
      rates were 47.8% and 34.5%, respectively. Three fixed factors (circulating blast
      > 3%, high cytogenetic risk, and high comorbidity index) and 2 factors (which
      are) modifiable by clinicians (myeloablative conditioning [MAC] and low-dose
      [<7.5 mg/kg] antithymocyte globulin [ATG]) were independent factors for poor
      GRFS. Based on these 5 factors, 3 groups (3-year GRFS: 64.9% in low risk, 33.6%
      in intermediate risk, and 6.6% in high risk; P < .001) were identified. Fixed
      factor-adjusted GRFS in patients receiving reduced-intensity conditioning (RIC)
      plus high-dose ATG (>=7.5 mg/kg) was superior (P < .001) to those receiving MAC
      and/or low-dose ATG. Favorable influences of RIC plus ATG >= 7.5mg/kg were
      evident in the low-risk group defined by fixed factors (3-year GRFS, 38.9% versus
      4.4%; P < .001) but were not evident in the high-risk group (3-year GRFS, .0%
      versus 5.3%; P = .678). Conclusively, this study suggests that risk-adapted
      selection of conditioning intensity and ATG could improve qualified HSCT
      outcomes.

PMID- 30103019
TI  - High-Sensitivity Troponin T and Incident Heart Failure in Older Men: British
      Regional Heart Study.
AB  - OBJECTIVE: The aim of this work was to study the association of high-sensitivity
      troponin T (hsTnT) with incident heart failure (HF), and implications for its use
      in prediction models. METHODS AND RESULTS: In the British Regional Heart Study,
      3852 men aged 60-79years without baseline HF (3165 without baseline chronic heart
      disease) were followed for a median of 12.6years, during which 295 incident cases
      of HF occurred (7.7%). A 1-SD increase in log-transformed hsTnT was associated
      with a higher risk of incident HF after adjusting for classic risk factors
      (hazard ratio [HR] 1.58, 95% confidence interval [CI] 1.42-1.77) and after
      additional adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP;
      HR 1.34, 95% CI 1.19-1.52). The strength of the association between hsTnT and
      incident HF did not differ by strata of other risk factors. An hsTnT
      concentration of <5ng/L had a sensitivity of 99.7% (95% CI 98.1%-99.9%) and a
      specificity of 3.4% (95% CI 2.8%-4.0%). A risk-prediction model including classic
      risk factors and NT-proBNP yielded a C-index of 0.791, but addition of hsTnT did
      not further improve prediction (P = .28). CONCLUSIONS: Elevated hsTnT is
      consistently associated with risk of HF in older men. HF occurred rarely over
      12years when baseline hsTnT was below the limit of detection. hsTnT measurement,
      however, does not improve HF prediction in a model already containing NT-proBNP.

PMID- 30103020
TI  - Decoupling Between Diastolic Pulmonary Arterial Pressure and Pulmonary Arterial
      Wedge Pressure at Incremental Left Ventricular Assist Device (LVAD) Speeds Is
      Associated With Worse Prognosis After LVAD Implantation.
AB  - BACKGROUND: Decoupling between diastolic pulmonary arterial pressure (dPAP) and
      pulmonary arterial wedge pressure (PAWP) is an index of pulmonary vasculature
      remodeling and provides prognostic information. Furthermore, decoupling may
      change during incremental left ventricular assist device (LVAD) speed changes.
      METHODS AND RESULTS: In this prospective study, patients underwent an
      echocardiographic and hemodynamic ramp test after LVAD implantation and were
      followed for 1 year. The change in decoupling (dPAP - PAWP) between the lowest
      and highest LVAD speeds during the ramp test was calculated. Survival and heart
      failure admission rates were assessed by means of Kaplan-Meier analysis. Eighty
      seven patients were enrolled in the study: 54 had a Heartmate II LVAD (60.8 +/-
      9.3 years of age and 34 male) and 33 had an HVAD LVAD (58.6 +/- 13.2 years of age
      and 20 male). Patients who experienced greater changes in decoupling
      (Deltadecoupling >3 mm Hg) had a persistently elevated dPAP at incremental LVAD
      speed and had worse 1-year heart failure readmission-free survival compared with
      the group without significant changes in the degree of decoupling (41% vs 75%; P
      = .001). CONCLUSIONS: An increase in decoupling between dPAP and PAWP at
      incremental LVAD speed changes was associated with worse prognosis in LVAD
      patients.

PMID- 30103022
TI  - Parvovirus B19 in Endomyocardial Biopsy of Patients With Idiopathic Dilated
      Cardiomyopathy: Foe or Bystander?
AB  - BACKGROUND: Parvovirus B19 (PVB19) has emerged as one of the viruses possibly
      inducing chronic myocarditis and subsequent idiopathic dilated cardiomyopathy
      (IDCM). The aim of this work was to investigate the presence and long-term
      consequences of PVB19-DNA within myocardial biopsies from patients with IDCM and
      to compare the findings with those from donor hearts (control group). METHODS AND
      RESULTS: Forty hospitalized IDCM patients (age 47 +/- 12 y) with mean left
      ventricular ejection fraction 27 +/- 12% were included. The presence of PVB19-DNA
      in myocardial biopsies and of IgG and IgM antibodies in patient sera was
      analyzed. The control group consisted of 20 donor hearts. The follow-up time was
      112 +/- 57 months. PVB19-DNA was found in myocardial biopsies of both patients
      (73%) and control samples (55%; P = .25).Three deaths and 8 heart
      transplantations occurred in the IDCM group, and 6 deaths in the control group
      (ie, the recipients of the control hearts). No difference in transplantation-free
      survival between the PVB19-DNA positive/negative IDCM patients or transplant
      recipients was found. CONCLUSIONS: PVB19-DNA is a common finding in both patients
      with IDCM and in healthy donor hearts, not affecting prognosis. These findings
      support the view that PVB19 is an innocent bystander, frequently found in
      myocardium with low DNA copies, and not a plausible cause of IDCM.

PMID- 30103021
TI  - Alveolar Air and O2 Uptake During Exercise in Patients With Heart Failure.
AB  - BACKGROUND: Peak exercise pulmonary oxygen uptake (VO2) is a primary marker of
      prognosis in heart failure (HF). The pathophysiology of impaired peak VO2 is
      unclear in patients. To what extent alveolar airway function affects VO2 during
      cardiopulmonary exercise testing (CPET) has not been fully elucidated. This study
      aimed to describe how changes in alveolar ventilation (VA), volume (VA), and
      related parameters couple with exercise VO2 in HF. METHODS AND RESULTS: A total
      of 35 patients with HF (left ventricular ejection fraction 20 +/- 6%, age 53 +/-
      7 y) participated in CPET with breath-to-breath measurements of ventilation and
      gas exchange. At rest, 20 W, and peak exercise, arterial CO2 tension was measured
      via radial arterial catheterization and used in alveolar equations to derive VA
      and VA. Resting lung diffusion capacity for carbon monoxide (DLCO) was assessed
      and indexed to VA for each time point. Resting R2 between VO2 and VA, VA, DLCO,
      and DLCO/VA was 0.68, 0.18, 0.20, and 0.07, respectively (all P < .05 except
      DLCO/VA). 20 W R2 between VO2 and VA, VA, DLCO, and DLCO/VA was 0.64, 0.32, 0.07,
      and 0.18 (all P < .05 except DLCO). Peak exercise R2 between VO2 and VA, VA,
      DLCO, and DLCO/VA was 0.55, 0.31, 0.34, and 0.06 (all P < .05 except DLCO/VA).
      CONCLUSIONS: These data suggest that alveolar airway function that is not
      exclusively related to effects caused by localized lung diffusivity affects
      exercise VO2 in moderate-to-severe HF.

PMID- 30103023
TI  - 17alpha-Ethinyl-androst-5-ene-3beta, 17beta-diol, a novel potent oral
      radioprotective agent, confers radioprotection of hematopoietic stem and
      progenitor cells in a granulocyte colony stimulating factor-independent manner.
AB  - PURPOSE: The risk of radiation exposure is considered to have increased in recent
      years. For convenience and simple administration, development of an effective
      orally administered radioprotective agent is highly desirable. The steroid 5-AED
      has been evaluated as both a radioprotector and a radiomitigator in mice and
      nonhuman primates, however, poor oral bioavailability has limited its
      development, while a variant compound, 17alpha-Ethinyl-androst-5-ene-3beta,
      17beta-diol (EAD), exhibits significant oral bioavailability. We investigated the
      radioprotective effects of EAD via oral administration in mice. METHODS AND
      MATERIALS: Survival assays were performed in lethally (9.0-10.0 Gy) irradiated
      mice. peripheral blood cell counts were monitored in lethally (9.5 Gy) or
      sublethally (6.5 Gy) irradiated mice. Histological analysis of bone marrow (BM),
      and frequency and functional analysis of hematopoietic stem and progenitor cells
      (HSPCs) in 6.5 Gy irradiated mice were performed. To investigate multilineage
      engraftment of irradiated HSCs after BM transplantation, competitive repopulation
      assays were conducted. Plasma granulocyte-colony stimulating factor (G-CSF) was
      measured by ELISA. RESULTS: Oral administration of EAD on 3 consecutive days
      before irradiation conferred 100% survival in mice, against otherwise 100% death,
      at a 9.5 Gy lethal dose of total body radiation. EAD ameliorated radiation
      induced pancytopenia at the same dose. EAD augmented BM cellular recovery and
      colony-forming ability, promoted HSPC recovery, and expanded the pool of
      functionally superior hematopoietic stem cells in the BM of sublethally
      irradiated mice. Unlike 5-AED, EAD did not increase G-CSF levels in mice and
      exhibited no therapeutic effects on hematological recovery post-irradiation;
      nevertheless, its radioprotective efficacy was superior to that of 5-AED.
      CONCLUSIONS: Our findings demonstrate the radioprotective efficacy of EAD and
      reveal that the 17alpha-Ethinyl group is essential for its oral activity. Given
      its oral efficacy and low toxicity, EAD has potential as an optimal
      radioprotector for use by first responders as well as at-risk civilian
      populations.

PMID- 30103024
TI  - Toward Biomarker-Informed Trimodality Therapy (TMT) Approaches for Muscle
      Invasive Bladder Cancer.

PMID- 30103025
TI  - The impact of wearable motion sensing technology on physical activity in older
      adults.
AB  - BACKGROUND AND PURPOSE: Physical activity provides substantial health benefits.
      Older adults are less physically active than the rest of the population, and
      interventions that promote physical activity are needed. In this meta-analysis,
      we investigate how different wearable activity trackers (pedometers and
      accelerometers) may impact physical activity levels in older adults. METHODS: We
      searched MEDLINE, Embase and CINAHL for randomized controlled trials including
      participants that were >=65 years, using wearable activity trackers with the
      intent of increasing physical activity. Studies whose comparator groups were
      engaged in active or inactive interventions, such as continued a physical therapy
      program or goal-setting counseling, were not excluded simply for implementing co
      interventions. We used random-effects models to produce standardized mean
      differences (SMDs) for physical activity outcomes. Heterogeneity was measured
      using I2. RESULTS: Nine studies met the eligibility criteria: Four using
      accelerometers, four using pedometers, and one comparing accelerometers and
      pedometers, for a total number of 939 participants. Using pooled data, we found a
      statistically significant effect of using accelerometers (SMD = 0.43 (95%CI 0.19
      0.68), I2 = 1.6%, p = 0.298), but not by using pedometers (SMD = 0.17 (95%CI 
      0.08-0.43), I2 = 37.7%, p = 0.174) for increasing physical activity levels.
      DISCUSSION AND CONCLUSIONS: In this study, we found that accelerometers, alone or
      in combination with other co-interventions, increased physical activity in older
      adults however pedometers were not found to increase physical activity. The high
      risk of bias found in most studies limits these findings. High quality studies
      that isolate the effects of accelerometers on physical activity changes are
      needed.

PMID- 30103027
TI  - Targeted proteomics: Bench to bedside.

PMID- 30103026
TI  - Effect of acute muscle contusion injury, with and without dietary fish oil, on
      adult and aged male rats: contractile and biochemical responses.
AB  - AIM: Contusion injury in aging muscle has not been studied in detail, but older
      adults are at risk for such injuries due to increased risk of falls. As falls in
      older populations are unlikely to be eliminated, interventions to minimize the
      negative impact of falls, including contusion injury should be pursued. Dietary
      fish oil (FO) is a common often supplement in older adults, which is associated
      with factors that might reduce or worsen the negative impact of contusion.
      METHODS: Here, we investigate whether 8 weeks of FO can blunt the impact of
      contusion injury in adult (n = 14) and aged (n = 12) rats. We assessed
      contractility and several biochemical markers in adult and aged gastrocnemius
      muscles 48 h post-contusion injury, using the uninjured muscles as controls.
      RESULTS: Injury reduced force production ~40% (P < 0.001), sarcoplasmic reticulum
      calcium release by ~20% (P = 0.003) and significantly increased several markers
      of muscle damage (i.e., protein carbonyls, Grp78 abundance (P = 0.022, 0.006,
      respectively)), and these injury-related changes were not affected by aging. The
      effects of FO were limited. A main effect (P = 0.018) for FO to increase the
      myogenic factor Myf5 was observed. In addition FO reduced the injury-associated
      decline in the mitophagy factor DRP1 (P = 0.027). CONCLUSION: Although age
      related differences in certain protein markers differed, aged muscles exhibited
      no greater acute functional deficits following injury. Similarly, while FO did
      not reduce functional deficits, it did not worsen them. However, changes in Myf5
      and DRP1 with dietary FO suggest the potential to improve recovery from contusion
      injury, which should be investigated in future studies.

PMID- 30103028
TI  - POPCORN: A web service for individual PrognOsis prediction based on multi-center
      clinical data CollabORatioN without patient-level data sharing.
AB  - BACKGROUND AND OBJECTIVE: Clinical prognosis prediction plays an important role
      in clinical research and practice. The construction of prediction models based on
      electronic health record data has recently become a research focus. Due to the
      lack of external validation, prediction models based on single-center, hospital
      specific datasets may not perform well with datasets from other medical
      institutions. Therefore, research investigating prognosis prediction model
      construction based on a collaborative analysis of multi-center electronic health
      record data could increase the number and coverage of patients used for model
      training, enrich patient prognostic features and ultimately improve the accuracy
      and generalization of prognosis prediction. MATERIALS AND METHODS: A web service
      for individual prognosis prediction based on multi-center clinical data
      collaboration without patient-level data sharing (POPCORN) was proposed. POPCORN
      focuses on solving key issues in multi-center collaborative research based on
      electronic health record systems; these issues include the standardization of
      clinical data expression, the preservation of patient privacy during model
      training and the effect of case mix variance on the prediction model construction
      and application. POPCORN is based on a multivariable meta-analysis and a Bayesian
      framework and can construct suitable prediction models for multiple clinical
      scenarios that can effectively adapt to complex clinical application
      environments. RESULTS: POPCORN was validated using a joint, multi-center
      collaborative research network between China and the United States with patients
      diagnosed with colorectal cancer. The performance of the models based on POPCORN
      was comparable to that of the standard prognosis prediction model; however,
      POPCORN did not expose raw patient data. The prediction models had similar AUC,
      but the BMA model had the lowest ECI across all prediction models, indicating
      that this model had better calibration performance than the other models,
      especially for patients in Chinese hospitals. CONCLUSIONS: The POPCORN system can
      build prediction models that perform well in complex clinical application
      scenarios and can provide effective decision support for individual patient
      prognostic predictions.

PMID- 30103029
TI  - Skin lesion classification with ensembles of deep convolutional neural networks.
AB  - Skin cancer is a major public health problem with over 123,000 newly diagnosed
      cases worldwide in every year. Melanoma is the deadliest form of skin cancer,
      responsible for over 9000 deaths in the United States each year. Thus, reliable
      automatic melanoma screening systems would provide a great help for clinicians to
      detect the malignant skin lesions as early as possible. In the last five years,
      the efficiency of deep learning-based methods increased dramatically and their
      performances seem to outperform conventional image processing methods in
      classification tasks. However, this type of machine learning-based approaches
      have a main drawback, namely they require thousands of labeled images per classes
      for their training. In this paper, we investigate how we can create an ensemble
      of deep convolutional neural networks to improve further their individual
      accuracies in the task of classifying dermoscopy images into the three classes
      melanoma, nevus, and seborrheic keratosis when we have no opportunity to train
      them on adequate number of annotated images. To achieve high classification
      accuracy, we fuse the outputs of the classification layers of four different deep
      neural network architectures. More specifically, we propose the aggregation of
      robust convolutional neural networks (CNNs) into one framework, where the final
      classification is achieved based on the weighted output of the member CNNs. For
      aggregation, we consider different fusion-based methods and select the best
      performing one for this problem. Our experimental results also prove that the
      creation of an ensemble of different neural networks is a meaningful approach,
      since each of the applied fusion strategies outperforms the individual networks
      regarding classification accuracy. The average area under the receiver operating
      characteristic curve has been found to be 0.891 for the 3-class classification
      task. For an objective evaluation of our approach, we have tested its performance
      on the official test database of the IEEE International Symposium on Biomedical
      Imaging (ISBI) 2017 challenge on Skin Lesion Analysis Towards Melanoma Detection
      dedicated to skin cancer recognition.

PMID- 30103030
TI  - Relationship between sagittal radiographic parameters and disability in patients
      with spinal disease using 3D standing analysis.
AB  - PURPOSE: To clarify the relationship between whole body sagittal radiographic
      parameters and health related quality of life (HRQOL) in patients with spinal
      disease, and further analyse such relationship based on the pelvic incidence (PI)
      value. METHODS: 100 patients (mean age: 64.4 years, M/F=50/50) with lumbar
      degenerative disease or spinal deformity were prospectively investigated.
      Following oswestry disability index (ODI) and scoliosis research society score 22
      (SRS-22) questionnaire, whole body sagittal x-ray parameters were measured using
      a slot-scanning 3D x-ray imager (EOS). Correlations between such radiographic
      parameters and ODI/SRS-22 scores were analysed. Then, patients were divided into
      three groups based on the PI value (PI<=45 degrees , 45<PI<=60 degrees , and
      60<PI), and correlations between the significantly correlated parameters and
      ODI/SRS-22 scores were analysed for each PI group. RESULTS: C2-7 lordosis, pelvic
      tilt (PT), pelvic incidence (PI), PI minus lumbar lordosis (PI-LL), sagittal
      vertical axis (SVA), full balance integrated index (FBI), and knee flexion angle
      (KneeFlex) had a significant correlation with ODI or SRS-22 scores. Among those
      parameters, PI and FBI showed a significant correlation with both ODI and SRS-22
      scores. High PI (>60 degrees ) group showed a strong correlation (R>0.4) with
      both ODI and SRS-22 scores for PI-LL parameter. CONCLUSIONS: PI and FBI showed a
      significant correlation with both ODI and SRS-22 scores. PI-LL mismatch was
      strongly correlated with disability in high PI patients. Our study results may
      indicate that it is important to pay attention to the PI value in addition to the
      spinopelvic relationship. LEVEL OF EVIDENCE: II, prospective study.

PMID- 30103031
TI  - Combination therapy with montelukast and loratadine alleviates pharyngolaryngeal
      symptoms related to seasonal allergic rhinitis.

PMID- 30103032
TI  - The role of co-rumination and adrenocortical attunement in young women's close
      friendships.
AB  - Attunement, or synchrony, of behavior and physiology has been well documented in
      family, mother-child, and romantic relationships. This study aimed to determine
      whether attunement of the hypothalamic-pituitary-adrenal (HPA) axis occurs in
      women's close friendships, and the role of a common social style, co-rumination
      in that attunement. Saliva samples (later assayed for cortisol) were collected
      from 37 dyads (74 individuals) during a laboratory task in which they were either
      asked to work together toward a common goal (control task) or discuss
      interpersonal problems, providing opportunity for co-rumination. Findings suggest
      that friends demonstrated adrenocortical attunement prior to engaging in either
      task, and that the level of attunement prior to the task predicted co-rumination
      and its components for both groups. Co-rumination, in turn, predicted
      adrenocortical attunement after the task. These findings suggest that
      bidirectional attunement of HPA activity may serve a bonding function within
      women's close friendships. Implications for how these findings fit with the tend
      and-befriend hypothesis are discussed.

PMID- 30103033
TI  - Greater reliance on the eye region predicts better face recognition ability.
AB  - Interest in using individual differences in face recognition ability to better
      understand the perceptual and cognitive mechanisms supporting face processing has
      grown substantially in recent years. The goal of this study was to determine how
      varying levels of face recognition ability are linked to changes in visual
      information extraction strategies in an identity recognition task. To address
      this question, fifty participants completed six tasks measuring face and object
      processing abilities. Using the Bubbles method (Gosselin & Schyns, 2001), we also
      measured each individual's use of visual information in face recognition. At the
      group level, our results replicate previous findings demonstrating the importance
      of the eye region for face identification. More importantly, we show that face
      processing ability is related to a systematic increase in the use of the eye
      area, especially the left eye from the observer's perspective. Indeed, our
      results suggest that the use of this region accounts for approximately 20% of the
      variance in face processing ability. These results support the idea that
      individual differences in face processing are at least partially related to the
      perceptual extraction strategy used during face identification.

PMID- 30103034
TI  - Transmissibility and severity of influenza virus by subtype.
AB  - The characteristics of influenza might vary depending on the disease subtype.
      This review includes previous studies on the transmissibility and severity of
      influenza and summarizes them by subtype. The attack rate and incubation period
      of influenza A were 2.3-12.3% and 1.4 days, respectively, and those of influenza
      B were 0.6-5.5% and 0.6 days, respectively. The five subtypes of influenza A
      virus, namely, H1N1, H2N2, H3N3, H5N1, and H7N9, are reviewed. The indexes
      related to transmissibility (reproduction number, attack rate, serial interval,
      latent period, incubation period, infectious period) and severity
      (hospitalization rate, case fatality rate) differed by influenza subtype.
      Generally, H3N2 showed a higher attack rate than H1N1 and H2N2. Additionally,
      H5N1 and H7N9 showed higher mortality rates than the other subtypes, including
      H1N1, H2N2, H3N2.

PMID- 30103035
TI  - Severe gynaecological involvement in Proteus Syndrome.
AB  - Proteus Syndrome is a rare complex overgrowth syndrome. We report a young female
      patient with Proteus Syndrome due to AKT1 mutation c.49G > A (p.Glu17Lys),
      presenting with a severe gynaecological involvement which necessitated a complete
      hysterectomy and a left adnexectomy. Cases of gynecological involvements in
      Proteus Syndrome are rare, not well known by physicians while they can be
      potentially severe.

PMID- 30103036
TI  - Further delineation of TBCK - Infantile hypotonia with psychomotor retardation
      and characteristic facies type 3.
AB  - Deleterious homozygous or compound heterozygous mutations in the TBCK (TBC1
      domain-containing kinase) gene (implicated in the MTOR pathway) produce profound
      hypotonia, global developmental delay, facial dysmorphic features, and brain
      abnormalities. The disorder has been named "infantile hypotonia with psychomotor
      retardation and characteristic facies-3" (IHPRF3). Here we present two sisters
      with a novel mutation in TBCK (NM_001163435.2: c.753dup; p.(Lys252*)) who have
      this ultrarare disorder. We have reviewed the literature on the 33 previously
      reported cases to provide a characterization of this emerging phenotype.
      Pathogenic mutations in TBCK have a predominant involvement of the Central
      Nervous System with a progressive pattern, leading to the conclusion where
      pathogenic mutations of the said gene lead to a progressive neurodegenerative
      disease. This report adds novel mutation and features to this complex phenotype.
      Further investigation is required to understand the pathogenesis of TBCK.

PMID- 30103037
TI  - Predicting the impacts of climate change, soils and vegetation types on the
      geographic distribution of Polyporus umbellatus in China.
AB  - Polyporus umbellatus is a fungus that has been used medically as a diuretic for
      thousands of years in China. To evaluate the impacts of climatic change on the
      distribution of P. umbellatus, we selected the annual mean air temperature,
      isothermality, minimum temperature of the coldest month, annual temperature
      range, annual precipitation and precipitation seasonality and used observations
      from the 2000s and simulated values from two future periods (2041 to 2060 and
      2061 to 2080) to build an ensemble model (EM); then, we developed a comprehensive
      habitat suitability model by integrating soil and vegetation conditions into the
      EM to assess the distribution of suitable P. umbellatus habitats across China in
      the 2000s and the two future periods. Our results show that annual precipitation
      and annual mean air temperature together largely determine the distribution of P.
      umbellatus and those suitable P. umbellatus habitats generally occur in areas
      with an optimal annual precipitation of approximately 1000 mm and an optimal
      annual mean air temperature of approximately 13  degrees C. In other words, P.
      umbellatus requires a humid and cool environment for growth. In addition, brown
      soils with a granular structure and low acidity are more suitable for P.
      umbellatus. Furthermore, we have observed that the distribution of P. umbellatus
      is usually associated with the presence of coniferous, mixed coniferous, and
      broad-leaved forests, suggesting that these vegetation types are suitable
      habitats for P. umbellatus. In the future, annual precipitation and annual mean
      air temperature will continue to increase, consequently increasing the
      availability of habitats suitable for P. umbellatus in northeastern and
      southwestern China but likely leading to a degradation of suitable P. umbellatus
      habitats in central China.

PMID- 30103038
TI  - Enterovesical Fistula in an Elderly Crohn's Disease Patient.

PMID- 30103039
TI  - A Multicenter Study Into Causes of Severe Acute Liver Injury.
AB  - The differential diagnosis of an increase in alanine aminotransferase (ALT) level
      and/or aspartate aminotransferase (AST) level of >=1000 IU/L often is stated to
      include 3 main etiologies: ischemic hepatitis, acute viral hepatitis (typically
      hepatitis A and hepatitis B), and drug-induced (more specifically,
      acetaminophen/paracetamol) liver injury (DILI).1 Unfortunately, there are a
      paucity of studies examining the most common causes of acute liver injury (ALI)
      and those that have been published have been small,2 single-center,2 or examined
      less severe increases in ALT or AST levels.3,4 We conducted a multicenter study
      of all patients with an ALT and/or AST level >=1000 IU/L. Our study had 3 main
      goals: (1) to determine the most common causes of an ALT and/or AST level >=1000
      IU/L, along with their relative frequencies; (2) to determine differences in
      etiology based on hospital type (liver transplant center, community hospital,
      Veterans Affairs hospital); and (3) to confirm or disprove the differential
      heuristic that ischemic hepatitis, acute viral hepatitis, and acetaminophen
      toxicity are the most common etiologies.

PMID- 30103040
TI  - The Association Between Perceived Stress and Quality of Life in University
      Students: The Parallel Mediating Role of Depressive Symptoms and Health-Promoting
      Behaviors.
AB  - PURPOSE: This study examined whether depressive symptoms and health-promoting
      lifestyle behaviors mediate the association between perceived stress and quality
      of life (QoL) in university students. METHODS: Using a cross-sectional survey,
      Korean university students (N = 187, Mage = 23.97 years; 54.0% Woman) completed
      structured questionnaires with psychometric adequacy. A parallel multiple
      mediation model was used to test the mediating effect of depressive symptoms and
      health-promoting lifestyle behaviors on the relationship between perceived stress
      and QoL. RESULTS: Total effect of perceived stress, depressive symptoms, and
      health-promoting lifestyle behaviors on QoL was -.55. Of these, total indirect
      mediating effect was -.50, whereas direct effect was only -.05 in the parallel
      mediation model. In particular, depressive symptoms (indirect effect = -.32) and
      health-promoting lifestyle behaviors (indirect effect = -.18) completely mediated
      the relationship between perceived stress and QoL. CONCLUSION: The results
      suggest that effective strategies primarily focusing on improving depressive
      symptoms along with health behaviors are needed to decrease the negative effect
      of perceived stress on QoL.

PMID- 30103042
TI  - Rheumatic immune-related adverse events in patients on anti-PD-1 inhibitors:
      Fasciitis with myositis syndrome as a new complication of immunotherapy.
AB  - OBJECTIVE: To evaluate the prevalence and type of rheumatic immune-related
      adverse events (IRAEs) in patients receiving programmed cell death protein-1 (PD
      1) inhibitors. METHODS: This is a single-center prospective observational study,
      including all cancer patients receiving PD-1 inhibitors between January 2016 and
      January 2018. RESULTS: During the period analyzed, we evaluated a total of 11
      patients. No patient had pre-existing rheumatic or autoimmune disease. In this
      period, a total of 220 patients were treated with PD1 inhibitors in our center;
      therefore, the estimated minimum prevalence of rheumatic IRAEs related to these
      therapies in our population was 5%. The rheumatic IRAEs evaluated included 5
      cases of oligo- or polyarthritis, 1 with a polymialgia rheumatica-type syndrome,
      2 cases of immunotherapy-induced sicca syndrome, 2 patients who presented
      symptomatic inflammatory myositis with fasciitis in lower extremities, and 1
      patient with a paraneoplastic acral vascular syndrome. The median time to IRAE
      after anti-PD1 exposure was 8 weeks (range: 2-24). In 5 patients, immunotherapy
      was discontinued (due to the adverse effect in three and cancer progression in
      two). In general terms the symptoms resolved completely with symptomatic
      treatment. Disease-modifying antirheumatic drugs were needed for 2 patients.
      CONCLUSION: Rheumatic IRAEs should be kept in mind during the follow-up and
      evaluation of patients treated with PD-1 inhibitors. The concomitant development
      of symptomatic inflammatory myositis with fasciitis in lower extremities appears
      to be a new adverse effect of anti-PD-1 immunotherapy. Additional studies are
      needed to determine how to adequately control and manage these complications.

PMID- 30103041
TI  - Clinical and immunological parameters of Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disease that primarily affects
      the exocrine glands, resulting in their functional impairment. In SS, lymphocytic
      infiltration of salivary and lacrimal glands, and deposition of several types of
      autoantibodies, mainly anti-SS-A (anti-Ro) and anti-SS-B (anti-La), lead to
      chronic inflammation, with xerostomia and keratoconjunctivitis sicca. In its
      primary form (pSS), SS does not involve additional connective tissue diseases,
      whereas in its secondary and more common form (sSS), SS presents in association
      with other rheumatic autoimmune diseases, mainly rheumatoid arthritis (RA),
      systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). As in most
      autoimmune diseases, environmental, hormonal and genetic factors are implicated
      in SS pathogenesis. In SS T cells predominate in mild lesions, whereas B cells
      predominate in advanced lesions. Th1, Th2, Th17, follicular helper T (Tfh) cells
      and regulatory cells (Tregs/Bregs), with their characteristic cytokine profiles,
      have been implicated in the pathogenesis of SS. It has been suggested that Th1
      and Th17 cells initiate SS and, as the disease progresses, Th2 and Tfh cells
      predominate. It is assumed that, as in all autoimmune and inflammatory
      conditions, tolerance defects contribute to SS pathogenesis. It is intriguing
      that in SS it remains unclear which types of regulatory cells are functional and
      whether they ameliorate or worsen the disease. In this review we present a
      comprehensive update on SS with emphasis on immune system involvement, and
      suggest new insights into SS immunopathogenesis.

PMID- 30103043
TI  - Molecular and cellular pathogenesis of heparin-induced thrombocytopenia (HIT).

PMID- 30103047
TI  - New insights into the etiopathogenesis of Hashimoto's Thyroiditis: The role of
      genetics and epigenetics.

PMID- 30103045
TI  - Increased risk of thrombosis in antiphospholipid syndrome patients treated with
      direct oral anticoagulants. Results from an international patient-level data meta
      analysis.
AB  - BACKGROUND: Direct oral anticoagulants (DOACs) are widely used for secondary
      prevention of venous thromboembolism (VTE) but their clinical efficacy and safety
      are not established in Antiphospholipid Syndrome (APS) patients. There is only
      one randomized controlled trial published while others are still ongoing. Many
      non-randomized studies have been published in this field with conflicting
      opinions. PURPOSE OF REVIEW: We conducted a systematic review using MEDLINE,
      EMBASE and Cochrane databases from 2000 until March 2018 regarding APS patients
      treated with DOACs. We performed a patient-level data meta-analysis to a)
      estimate the prevalence of recurrent thrombosis in APS patients treated with
      DOACs in the literature, and b) identify variables associated with recurrent
      thrombosis. RESULTS: We identified 47 studies corresponding to 447 APS patients
      treated with DOACs. Three commercially available DOACs were analyzed: rivaroxaban
      (n = 290), dabigatran etexilate (n = 144) and apixaban (n = 13). A total of 73
      out of 447 patients (16%) experienced a recurrent thrombosis while on DOACs with
      a mean duration until thrombosis of 12.5 months. Rates of recurrent thromboses
      were 16.9% and 15% in APS patients receiving either anti-Xa inhibitors or
      dabigatran respectively. Triple positivity (positivity for all three
      antiphospholipid antibodies) was associated with a four-fold increased risk of
      recurrent thrombosis (56% vs 23%; OR = 4.3 [95%CI; 2.3-7.7], p < 0.0001) as well
      as a higher number of clinical criteria for APS classification. In patients
      treated with anti-Xa inhibitors, history of arterial thrombosis was associated
      with a higher risk of recurrent thrombosis (32% vs 14%; OR = 2.8 [95%CI; 1.4
      5.7], p = 0.006). In conclusion, DOACs are not effective in all APS patients and
      should not be used routinely in these patients. Randomized controlled trials
      assessing clinical efficacy and safety as primary endpoints are underway. In the
      meantime, a registry of APS patients on DOACs could be proposed to establish in
      which APS subgroups DOACs would be a safe alternative to warfarin.

PMID- 30103046
TI  - Paraneoplastic autoimmune multiorgan syndrome (PAMS): Beyond the single phenotype
      of paraneoplastic pemphigus.
AB  - Paraneoplastic autoimmune multiorgan syndrome (PAMS) is characterized by a
      heterogenous group of signs and symptoms including severe desquamative
      stomatitis, a polymorphous cutaneous eruption, humoral immunity against plakin
      proteins, contribution of cell-mediated autoimmunity and commonly a progressive
      respiratory failure. Autoantibodies in PAMS target a wide array of antigens
      including plakins, cadherins, alpha-2-macroglobulin like 1 (A2ML1), BP180,
      plakophilin-3, and several neuromuscular antigens. Originally described as
      paraneoplastic pemphigus in 1990 due to some of its clinical and immunologic
      similarities to classic pemphigus (pemphigus vulgaris and pemphigus foliaceus),
      PAMS is a multiorganopathy with several distinct features from these classic
      forms of pemphigus. Epidemiologically, PAMS is associated with underlying
      neoplasia and has a differing HLA-II allele predisposition compared to classic
      forms of pemphigus. Clinically, lesion morphology is polymorphous, and lesion
      distribution fundamentally differs from that seen in classic pemphigus. PAMS has
      a significantly higher mortality rate and a poorer response to treatments
      typically effective in pemphigus. Histologically, PAMS is characterized by the
      presence of interface dermatitis, vacuolar changes, and dyskeratotic
      keratinocytes which are not seen in classic pemphigus. PAMS demonstrates not only
      intercellular IgG as seen in classic pemphigus, but the presence of linear
      basement membrane zone deposition. Antibodies against desmoglein 3 (Dsg3) map to
      a broader array of epitopes than in pemphigus vulgaris and there is a higher
      prevalence of complement binding anti-Dsg3 IgG autoantibodies in PAMS.
      Autoantibodies can in rare cases be absent in the more cell-mediated form of
      PAMS. Considering these numerable differences, we review the entity of PAMS, and
      provide similarities and differences to classic forms of pemphigus.

PMID- 30103048
TI  - Occurrence and fate of endotoxin activity at drinking water purification plants
      and healthcare facilities in Japan.
AB  - Occurrence of residual endotoxin activity (ET) in dialysis water and also tap
      water as its source is a matter of great concern to medical professionals
      conducting dialysis therapy at healthcare facilities (HCFs). The present study
      was performed to determine the occurrence and fate of the ET at selected Japanese
      drinking water purification plants and HCFs between 2014 and 2016. Chemical
      coagulation and sedimentation, rapid sand filtration, and membrane filtration
      were highly effective to decrease both ET dissolved in water (free-ET) and ET
      bound to cells/particles (bound-ET). Moderate decreases in bound-ET and limited
      decreases in free-ET were observed by chlorination and ozonation. Bacterial
      activated carbon filtration was a major cause of significant increases in
      endotoxin activity during the course of drinking water purification process.
      Levels of residual ET in water supplied to HCFs were strongly affected by their
      source waters and the configurations of water purification processes served.
      Microbial regrowth on the premises, from water tanks to faucets at HCFs could
      also contribute to ET increases in tap water.

PMID- 30103049
TI  - Sleep, Physical Activity, and General Health Status: US Pediatricians and the
      General US Adult Population.
AB  - OBJECTIVE: To examine US pediatricians and US adults on 3 self-reported health
      measures (sleep, physical activity, and general health status) and to assess
      factors related to these measures for each group. METHODS: Pediatrician data were
      collected through a 2012 American Academy of Pediatrics Periodic Survey (response
      rate = 64.0%). US population data originated from the 2012 National Health
      Interview Survey (response rate = 61.2%). Analytic samples included those
      currently working and >=30 years old and were restricted to post-trainees
      (pediatricians; n = 854) and US adults with at least a bachelor's degree (n =
      5447). Accounting for sample demographic differences, predicted probabilities
      compared the proportions reporting >=7 hours of sleep, meeting physical activity
      recommendations, and reporting very good or excellent health. Multivariable
      logistic regression examined characteristics associated with health measures for
      pediatricians and US adults separately. RESULTS: When the US population
      demographic profile was adjusted to resemble the pediatrician sample, 7 in 10
      pediatricians (71.2%; confidence interval [CI], 68.0-74.5) and US adults (69.9%;
      CI, 67.8-72.0) reported >=7hours of sleep. Pediatricians were more likely than US
      adults to meet physical activity recommendations (71.4%; CI, 68.0-74.8vs. 62.9%;
      CI, 60.6-65.2) and less likely to report very good or excellent health (74.3%;
      CI, 71.2-77.3vs. 80.2%; CI, 78.3-82.1). In pediatrician and US population
      multivariable models, self-identified Asians and those working >=50hours were
      less likely to get >=7hours of sleep (P < .05). CONCLUSIONS: Most US
      pediatricians and US adults reported getting the recommended amounts of sleep and
      physical activity and rated their health as very good or excellent. Those working
      fewer hours reported more sleep. Organization-directed approaches may be needed
      to help physicians maintain and improve their health.

PMID- 30103044
TI  - Recommendations and barriers to vaccination in systemic lupus erythematosus.
AB  - Patients with Systemic Lupus Erythematosus (SLE) pose a unique dilemma pertaining
      to immunization against common pathogens. SLE patients are usually not immunized
      with vaccines based on the fear of either precipitating infection in this
      immunosuppressed patient population (with live vaccines) or aggravating
      autoimmunity and hence lupus flares (with any vaccines). However, elevated
      vulnerability to infection makes patients with SLE precisely the population that
      needs protection from vaccine-preventable diseases. A summary of guidelines from
      the Centers for Disease Control and Prevention, professional societies, review
      articles and expert opinions regarding use of individual vaccines applicable to
      adults with SLE is presented in this review.

PMID- 30103050
TI  - Neonatal Intubation Competency Assessment Tool: Development and Validation.
AB  - BACKGROUND: Neonatal tracheal intubation (NTI) is an important clinical skill.
      Suboptimal performance is associated with patient harm. Simulation training can
      improve NTI performance. Improving performance requires an objective assessment
      of competency. Competency assessment tools need strong evidence of validity. We
      hypothesized that an NTI competency assessment tool with multisource validity
      evidence could be developed and be used for formative and summative assessment
      during simulation-based training. METHODS: An NTI assessment tool was developed
      based on a literature review. The tool was refined through 2 rounds of a modified
      Delphi process involving 12 subject-matter experts. The final tool included a 22
      item checklist, a global skills assessment, and an entrustable professional
      activity (EPA) level. The validity of the checklist was assessed by having 4
      blinded reviewers score 23 videos of health care providers intubating a neonatal
      simulator. RESULTS: The checklist items had good internal consistency (overall
      alpha = 0.79). Checklist scores were greater for providers at greater training
      levels and with more NTI experience. Checklist scores correlated with global
      skills assessment (rho = 0.85; P < .05), EPA levels (rho = 0.87; P < .05),
      percent glottic exposure (r = 0.59; P < .05), and Cormack-Lehane scores (rho =
      0.95; P < .05). Checklist scores reliably predicted EPA levels. CONCLUSIONS: We
      developed an NTI competency assessment tool with multisource validity evidence.
      The tool was able to discriminate NTI performance based on experience. The tool
      can be used during simulation-based NTI training to provide formative and
      summative assessment and can aid with entrustment decisions.

PMID- 30103051
TI  - Analysis of the Correlation Between Central Obesity and Abdominal Aortic
      Diseases.
AB  - BACKGROUND: Atherosclerosis and abdominal aortic aneurysms (AAAs) have several
      similar risk factors but different pathogenesis. Inflammation of the arteries is
      common to both. Central obesity can act as an endocrine organ through the
      secretion of inflammatory cytokines, and the perivascular fat has a local effect
      that could contribute to diseases of the abdominal aorta. Although the relation
      between central obesity and atherosclerosis occlusive arterial disease has been
      demonstrated, the correlation with AAA has conflicting results. The aim of this
      study was to analyze the correlation between central obesity and the presence of
      abdominal aortic diseases using computed tomography. METHODS: Six hundred thirty
      nine consecutive patients classified into 3 groups (AAA, aortic atherosclerotic
      occlusive disease (AAOD), and without aortic disease [control group]) who
      underwent computed tomography had the aorta diameter, the visceral fat area
      (VFA), and the subcutaneous fat area (SFA) measured at the level of third and
      fourth lumbar vertebrae. RESULTS: VFA showed no difference between the groups.
      SFA was lower in atherosclerotic group (AAOD) than control (P < 0.01 in general
      and P < 0.04 in male). In AAA group, we found in men that the first tertile of
      aorta diameter had higher VFA than third tertile (P = 0.02). CONCLUSIONS: There
      was no difference in VFA between patients in AAA, AAOD, and without aortic
      disease groups. In men with aneurysm, there was an inverse relationship between
      VFA and aortic diameter. In AAOD, visceral to subcutaneous ratio is higher due to
      lower SFA.

PMID- 30103052
TI  - Association of Serum SorLA with Intimal Hyperplasia after Carotid Endarterectomy
      Operation: A Retrospective Analysis.
AB  - BACKGROUND: To study the relevance between serum sorting protein-related receptor
      containing the low-density lipoprotein receptor class A (SorLA) and intimal
      hyperplasia (IH) after carotid endarterectomy (CEA) operation. METHODS: Seventy
      nine carotid artery stenosis patients receiving CEA operation from September 2013
      to March 2015 were included. Serum SorLA level was detected by enzyme linked
      immunosorbent assay method preoperatively. All the 79 patients received regular
      follow-up to diagnose the IH of target lesions, postoperatively. Based on the
      follow-up data, the patients were divided into IH group (n = 10) and non-IH group
      (n = 69). Serum SorLA levels were analyzed using t-test. Receiver-operating
      characteristic curve was applied to determine the value of serum SorLA to predict
      the occurrence of IH after CEA operation. RESULTS: Patients in severe IH group
      had a higher level of serum SorLA than patients in non-IH group (1.648 +/- 0.246
      ng/mL vs. 1.278 +/- 0.281 ng/mL, P < 0.001). When 1.44 ng/mL was designated as
      the cutoff value of serum SorLA, the predicting value had a sensitivity of 90%
      and a specificity of 73.5%. CONCLUSIONS: High serum SorLA level is related to IH
      after CEA operation. A serum SorLA level of 1.44 ng/mL can be used as a
      predicting index of postoperative IH.

PMID- 30103053
TI  - Correlation of Interleukin-18 and High-Sensitivity C-Reactive Protein with
      Perioperative Deep Vein Thrombosis in Patients with Ankle Fracture.
AB  - BACKGROUND: In the present study, we aimed to inspect the correlation of
      interleukin-18 (IL-18) and high-sensitivity C-reactive protein (hs-CRP), if any
      present, with the occurrence of perioperative deep vein thrombosis (DVT) in
      patients suffering from an ankle fracture (AF). METHODS: Sixty-seven AF patients
      with complicated DVT (DVT group) and 448 AF patients without DVT (non-DVT group)
      were enrolled in the present study. To begin with, hemorheological indexes were
      detected. Turbidimetric immunoassay and enzyme-linked immunosorbent assay were
      used for the determination of the expressions of hs-CRP and IL-18, respectively.
      Coagulation method was used to detect prothrombin time (PT), thrombin time (TT),
      fibrinogen, and activated partial thromboplastin time (APTT). Logistic regression
      analysis was used to analyze the independent risk factors for DVT occurrence in
      AF patients after operation. RESULTS: The results revealed that the DVT group
      presented an increased expression of hs-CRP and IL-18 1 day before operation and
      1, 3, and 7 days after operation in comparison with the non-DVT group. The DVT
      group also had increased levels of PT, APTT, and prolonged TT and fibrinogen at 3
      and 7 days after operation compared to the non-DVT group. After operation, it was
      observed that the patients in the DVT group had increased plasma viscosity, whole
      blood reduced viscosity, red blood cell (RBC) aggregation index, RBC deformation
      index, erythrocyte sedimentation rate, and declined erythrocrit. The independent
      risk factors for the occurrence of DVT were identified to be high-energy injury,
      TT, fibrinogen, hs-CRP, and IL-18 in AF patients after operation. CONCLUSIONS:
      Based on the results obtained from the study, it was concluded that AF patients
      with DVT have higher levels of IL-18 and hs-CRP expressions, which is associated
      with the occurrence and development of DVT. These results may be particularly
      useful for diagnosis and treatment on DVT occurrence in AF patients.

PMID- 30103054
TI  - The Neurosurgeon as a High-Performance Athlete: Parallels and Lessons Learned
      from Sports Psychology.
AB  - BACKGROUND: Top performing neurosurgeons and elite athletes require years of
      sacrifice, discipline, and dedication to their art to be finely attuned to their
      physical abilities and limitations, and a singular mental focus to reach their
      full potential under moments of pressure. METHODS: We outline strategies and
      techniques commonly used by high-performance athletes and how they may be applied
      to neurosurgery to achieve the highest possible surgeon preparation, patient
      outcomes, and career longevity. RESULTS: Further investigation and integration of
      well-established cognitive psychology applications to surgical performance is
      needed. These principles are broad-reaching and may be applied to the training of
      our residents, our own daily routine, and as a life philosophy to enhance the
      longevity of our careers. CONCLUSIONS: Maintaining peak performance for a
      neurosurgeon may prove to be more challenging than that of the elite athlete.

PMID- 30103055
TI  - Functional Independence After Stroke Thrombectomy Using Thrombolysis In Cerebral
      Infarction Grade 2c: A New Aim of Successful Revascularization.
AB  - BACKGROUND: Within the Thrombolysis In Cerebral Infarction (TICI) classification,
      TICI 2b has been historically considered successful recanalization. However, TICI
      2b may result in worse functional outcomes compared with TICI 3 or a proposed
      TICI 2c revascularization grade. The aim of this study was to evaluate
      differences in functional independence at 90 days between TICI 2b, 2c, and 3
      grades. METHODS: A retrospective review of 185 consecutive patients with anterior
      cerebral circulation occlusions was performed; 33 patients who were treated >8
      hours after onset were excluded. Patient angiograms were graded by 2 experienced
      neurointerventional physicians. Baseline demographics and functional independence
      at 90 days were compared. RESULTS: Of 152 patients included in the study, 113
      patients achieved TICI grade 2b (n = 37), 2c (n = 34), or 3 (n = 42). A
      significant difference in functional independence at 90 days was observed between
      TICI 2b and 2c/3 (P = 0.0008), between 2b and 2c (P = 0.0005), and between 2b and
      3 (P = 0.01). There was no significant difference in functional independence
      between 2c and 3 (P = 0.24). CONCLUSIONS: TICI 2c revascularization is associated
      with significantly improved outcomes compared with TICI 2b revascularization and
      similar outcomes compared with TICI 3 revascularization. Using a TICI grading
      system that includes an additional TICI 2c grade or expands the current
      definition of TICI 3 allows for refined prediction of functional independence.
      Achieving TICI 2c/3 reperfusion should be considered during stroke thrombectomy.

PMID- 30103056
TI  - Association of Neutrophil to Lymphocyte Ratio on 90-Day Functional Outcome in
      Patients with Intracerebral Hemorrhage Undergoing Surgical Treatment.
AB  - BACKGROUND: The inflammatory response plays a vital role in the pathologic
      mechanism of intracerebral hemorrhage. It recently has been reported that
      neutrophil to lymphocyte ratio (NLR) could represent a novel composite
      inflammatory marker for predicting the prognosis of intracranial hemorrhage
      (ICH). However, in considering the effects of surgical evacuation on the
      initiation of inflammatory responses, the relationship between NLR and functional
      outcome of patients with ICH after surgical treatment is still controversial.
      Here, we aimed to assess the predictive value of admission NLR and other
      available laboratory parameters for 90-day outcome of patients with ICH
      undergoing neurosurgical treatment. METHODS: In total, 104 patients with acute
      ICH admitted to West China Hospital from October 2016 to January 2018 were
      retrospectively enrolled. Admission absolute neutrophil count, lymphocyte count,
      and white blood count were extracted from electronic medical records of patents
      with ICH. The associations between outcome and laboratory biomarkers were
      assessed by multivariable logistic regression analysis. The comparison of
      predictive power of independent predictors was evaluated by receiver operating
      characteristic curves. RESULTS: In total, 59 patients with ICH who underwent
      surgical treatment exhibited unfavorable outcomes, which was associated with
      greater admission NLR (odds ratio [OR] 0.692, 95% confidence interval [CI] 0.518
      0.925, P = 0.01; OR 1.148, 95% CI 1.078-1.222, P < 0.01; OR 1.215, 95% CI 1.015
      1.454, P = 0.03), lower Glasgow Coma Scale score, and larger hematoma. NLR showed
      the best predictive power by comparing with other laboratorial variables (area
      under the curve 0.668, 95% CI 0.569-0.757, P < 0.01) and also was found to
      linearly correlate with Glasgow Coma Scale score at admission, hematoma volume,
      absolute neutrophil count, absolute lymphocyte count, and hydrocephalus.
      Meanwhile, the best predictive cutoff point of 6.46 for NLR also was identified.
      CONCLUSIONS: Other than the association of prognosis of patients with ICH, NLR
      exhibited potential independent predictive ability for 90-day functional outcomes
      of patients with ICH after surgery.

PMID- 30103057
TI  - Dural Arteriovenous Fistulas at the Petrous Apex.
AB  - OBJECTIVE: Dural arteriovenous fistulas (DAVFs) at the petrous apex are rare but
      may cause subarachnoid hemorrhage (SAH) or severe brainstem edema. This study
      aimed to summarize their clinical features and discuss the classification.
      METHODS: During a 15-year period, 64 consecutive patients with DAVF at the
      petrous apex were reviewed. According to their angioarchitecture, these cases
      were classified as follows: type I, no venous ectasia (48.4%); type II, venous
      ectasia but with normal vein proximal to the fistula (29.7%); and type III,
      venous ectasia at the site of the fistula (21.9%). RESULTS: There were 53 men and
      11 women included. Presented symptoms were SAH in 8 patients (12.5%),
      nonhemorrhagic neurologic defects (NHNDs) in 53 patients (82.8%), and no symptoms
      in 3 patients (4.7%). There were 49 patients who received transarterial
      embolization, 8 patients who received microsurgery, and 7 patients who received
      embolization and microsurgery. Complications occurred in 9 patients (14.1%),
      including transient cranial nerve palsy (4.7%), rebleeding (6.3%), and
      respiratory failure (3.1%). Of the type I patients, 96.77% presented with NHNDs
      and 77.42% presented with infratentorial drainage. However, SAH occurred more
      often in type II (21.05%)/type III cases (28.57%), and most patients carried a
      supratentorial drainage (63.16% and 85.71%, respectively). In different types of
      DAVFs, the necessity for embolization combined with microsurgery (6.45% in type
      I, 10.53% in type II, 21.43% in type III) and the occurrence of rebleeding
      complications (0% in type I, 10.53% in type II, and 14.29% in type III) were
      varied. CONCLUSIONS: Petrous apex DAVFs carried a high risk of embolization
      related complications. Based on the vascular architecture, this classification
      may reflect their clinical features and provide some advice on the treatment of
      DAVFs at the petrous apex.

PMID- 30103058
TI  - Final Infarct Volume of <10 cm3 is a Strong Predictor of Return to Home in
      Nonagenarians Undergoing Mechanical Thrombectomy.
AB  - BACKGROUND: Although elderly patients have generally worse outcomes after acute
      ischemic stroke, they may derive significant incremental benefit from
      thrombectomy as compared with medical management. Although several case series
      for octogenarians have been reported, data for nonagenarians are scarce. METHODS:
      A prospectively maintained institutional mechanical thrombectomy database was
      reviewed for nonagenarians who underwent thrombectomy between January 2013 and
      July 2017. Patient demographic data and clinical history data were extracted, and
      clinical and radiographic outcomes were assessed. Univariate analysis was used to
      determine correlation between treatment and radiographic data and outcome.
      RESULTS: During the study period, 30 patients >=90 years old underwent mechanical
      thrombectomy. Median National Institutes of Health Stroke Scale score on
      presentation was 20. Successful reperfusion (Thrombolysis In Cerebral Infarction
      2b/3) was achieved in 27 patients (90%). One patient (3%) was discharged to home,
      and 9 patients (30%) were discharged to a rehabilitation facility. The 90-day
      mortality was 70%. Six patients (21%) returned to living at home. All 6 patients
      had successful reperfusion after the procedure; average infarct burden on
      postthrombectomy neuroimaging was 1.5 cm3, and infarct volume was <7 cm3 in all
      cases. Final infarct volume of <10 cm3 was a strong predictor of whether a
      patient returned to live at home (P = 0.002), with a trend toward better outcome
      as assessed by modified Rankin Scale (P = 0.076). CONCLUSIONS: Large vessel
      thrombectomy in nonagenarians is safe and offers patients a chance at returning
      to functional baseline. All patients returning home in our cohort had successful
      recanalization and minimal stroke burden after thrombectomy.

PMID- 30103060
TI  - A Prospective Detailed Time Analysis Study of 18 Patients Undergoing Elective
      Single-Level Open Lumbar Microdiscectomy Spinal Surgery Compared with Centers for
      Medicare and Medicaid Services Reimbursement Guidelines.
AB  - BACKGROUND: Single-level open lumbar microdiscectomy surgery is one of the most
      straightforward and effective spinal surgeries performed by spinal surgeons today
      to treat disk herniation. Although a common operation, little in the literature
      is reported on the exact overall time, cost, and effort associated with the
      performance of this surgery. The consistency of this operation across
      institutions and disciplines makes it a good starting point to accurately track
      the total time and effort of all phases of the surgical intervention. METHODS:
      Eighteen patients undergoing elective single-level open lumbar microdiscectomy
      surgery were prospectively enrolled in this study. The time spent interacting
      with each patient by every member of the surgical team was tracked and recorded
      along will every phone call and e-mail. All perioperative times associated with
      the surgery were tracked and analyzed. Each patient was followed from their first
      interaction through surgery and for the first 3 months postoperatively. RESULTS:
      The advanced practice providers spent the most time with the patient both pre-
      and postoperatively followed by the surgeon and resident. A total of 2.98 hours
      was spent with the patient preoperatively in clinic and 1.69 hours
      postoperatively. The total time commitment of an institution treating this
      condition was 12.56 hours. CONCLUSIONS: Comparing our results with the Centers
      for Medicare and Medicaid Services data, a significant discrepancy and
      underestimation was observed. As such, we hope our results enable health care
      providers to more accurately allocate resources for the provision of high-quality
      medical care to patients with this increasingly common condition.

PMID- 30103059
TI  - Morphologic Feature Elongation Can Predict Occlusion Status Following Pipeline
      Embolization of Intracranial Aneurysms.
AB  - OBJECTIVE: To explore whether computed morphologic features can be used as
      independent predictors of incomplete occlusion of aneurysms treated with the
      Pipeline embolization device. METHODS: From January 2016 to September 2017, 58
      patients with 58 aneurysms were treated with the Pipeline embolization device.
      Aneurysms were manually segmented from the Digital Imaging and Communications in
      Medicine file, and we calculated 16 shape features voxel by voxel on the
      segmented aneurysm image. Along with 13 other clinical and radiographic
      variables, we performed univariate and multivariate analysis to explore
      predictors of incomplete occlusion. RESULTS: At last angiographic follow-up
      (median 6.2 months), complete occlusion was achieved in 41 aneurysms (70.7%). In
      multivariate analysis, malapposition of stent (odds ratio = 0.03; 95% confidence
      interval, 0.00-0.32; P = 0.004) and higher elongation value (odds ratio = 0.03;
      95% confidence interval, 0.01-0.17; P < 0.001) were independently associated with
      incomplete occlusion of aneurysms. Compared with aneurysms with complete
      occlusion, incompletely occluded aneurysms had higher elongation values (median
      0.890 vs. 0.766; P < 0.001); the optimal cutoff value of elongation for occlusion
      status classification was 0.862. Predicting accuracy, sensitivity, specificity,
      positive predictive value, negative predictive value, and area under the curve of
      the logistic regression model were 0.879, 0.902, 0.824, 0.925, 0.778, and 0.872.
      CONCLUSIONS: Malapposition of stent and higher elongation value were independent
      negative predictors of aneurysm occlusion following flow diversion.

PMID- 30103061
TI  - Perspectives from a Residency Training Program Following the Implementation of a
      Wellness Initiative.
AB  - BACKGROUND AND OBJECTIVES: Programs that address overall wellbeing early in
      residency are necessary to prevent physician burnout and promote physician mental
      health to improve patient outcomes and ensure long and productive careers. A
      wellness initiative was implemented at our institution 3 years ago. We present
      feedback from participating residents across all levels of training. METHODS: A
      17-question survey was administered to resident physicians in the department of
      neurosurgery at our institution. In addition to the resident survey results, we
      obtained personal perspective pieces from attendings and residents across all
      levels of training. RESULTS: A total of 8 resident physicians completed a 17
      question survey. 100% of participants felt that health and wellness initiatives
      are "very important" for resident physicians, that the initiative has been
      "largely positive" for the department overall, and that is has positively
      impacted their personal life in addition to their professional life. The majority
      (75%) of respondents indicated that participation has not affected patient care
      responsibilities "at all." CONCLUSIONS: Participating resident perceptions of the
      wellness program are highly favorable. The survey results, combined with the
      perspectives across training levels, provide insight for other programs wishing
      to implement program of their own.

PMID- 30103062
TI  - The presence of cerebral microbleeds is associated with cognitive impairment in
      Parkinson's disease.
AB  - BACKGROUND: Cerebral microbleeds (CMBs) are often observed in Parkinson's disease
      (PD); however, their association with cognitive decline has been unclear. We
      performed a retrospective analysis of 124 cases of clinically diagnosed PD to
      determine the association between the presence of CMBs and cognitive decline.
      RESULTS: Of the 124 participants, 21 (16.9%) was diagnosed as PDD in this cohort.
      CMBs were observed significantly more frequently in the PDD than in the PD (47.6%
      vs 7.8%, P < .001). The presence of both deep/infratentorial (40% vs 14.9%, P <
      .05) and strictly lobar (75% vs 12.9%, P < .001) CMBs were associated with PDD.
      The values of cognitive scales such as Mini-Mental State Examination and the
      Hasegawa Dementia Scale-revised, were also significantly lower in the presence of
      each type of CMB. A multivariable logistic regression analysis showed the
      presence of strictly lobar CMBs as well as a male gender, orthostatic
      hypotension, periventricular hyperintensity on magnetic resonance imaging were
      significantly associated with PDD in this cohort. CONCLUSIONS: This study showed
      the presence of CMBs, especially strictly lobar type, was strongly associated
      with PDD. We suspect that the burden of small vessel disease and cerebral amyloid
      angiopathy may be related to the development of cognitive decline in PD, and a
      prospective study enrolling more cases is warranted.

PMID- 30103063
TI  - Validity of probands' reports and self-reports of essential tremor: Data from a
      large family study in North America.
AB  - The search for genes for essential tremor (ET) is active. Researchers often
      depend on probands' reports or self-reports to assign disease status to
      relatives. Yet there are surprisingly few data on the validity of these reports.
      In two prior studies, with small sample sizes, validity was poor (sensitivity =
      16.7-43.3%). In the current study, ET probands and their relatives were screened
      for tremor and then underwent a videotaped in-person neurological examination.
      One investigator then assessed the screening questionnaires and videotapes to
      assign diagnoses of ET, borderline tremor or other diagnosis. There were 98
      probands and 243 relatives (105 with ET, 34 with borderline tremor). Educational
      attainment was high (15.6 +/- 2.7 years). Probands failed to report tremor in
      39/139 relatives with ET or borderline tremor; conversely, they reported tremor
      in 32/104 relatives without ET or borderline tremor. Thus, in total, there were
      71/243 (29.2%) mis-identifications. Thirty six of 139 ET and borderline ET cases
      failed to self-report tremor; conversely, 30/104 relatives without ET or
      borderline tremor self-reported tremor. Thus, in total, there were 66/243 (27.2%)
      mis-identifications. In summary, in individuals with greater educational
      attainment, the validity of reported information on ET was considerably higher
      than previously reported. Despite this, even among well-educated individuals in
      North America, probands' reports and self-reports misclassified approximately 30%
      (i.e., one-in-three) of relatives.

PMID- 30103064
TI  - Restless legs syndrome, leg motor restlessness and their variants in patients
      with Parkinson's disease and related disorders.
AB  - OBJECTIVE: The objective of this study was to investigate the prevalence of
      restless leg syndrome (RLS), leg motor restlessness (LMR) and RLS/LMR variants
      and their relationship with clinical factors in patients with Parkinson's disease
      (PD) and related disorders. METHODS: Sixty-three PD patients, 17 multiple system
      atrophy (MSA) patients and 11 progressive supranuclear palsy (PSP) patients were
      included in this study. Through face-to-face interviews, the patients were
      diagnosed with RLS/LMR, or with RLS/LMR variants in which the symptoms occur
      predominantly in body parts other than the legs. RESULTS: The frequency of RLS,
      LMR, RLS variants and LMR variants was as follows: PD (12.7%, 11.1%, 0% and
      1.6%); MSA (5.9%, 11.8%, 0% and 0%); and PSP (0%, 9.1%, 0% and 0%). Restlessness
      without the urge to move was observed in 25.4% of the PD patients, 11.8% of the
      MSA patients and 0% of the PSP patients. The PD patients with restlessness
      exhibited higher Hoehn and Yahr stages and higher scores on the Scales for
      Outcomes in PD-Autonomic, PD sleep scale-2 and Beck Depression Inventory-II. The
      olfactory functioning, 123I-MIBG myocardial scintigraphy uptake and dopamine
      transporter single photon emission computed tomography findings did not differ
      between the PD patients with restlessness and those without. The severity of RLS
      was correlated with the autonomic symptoms among the PD patients with
      restlessness. CONCLUSION: PD with restlessness was characterized by increased
      autonomic, sleep and depressive symptoms. Further studies including a large
      sample are warranted to characterize restlessness in PD and related disorders.

PMID- 30103065
TI  - Disease trajectories in behavioural variant frontotemporal dementia, primary
      psychiatric and other neurodegenerative disorders presenting with behavioural
      change.
AB  - Behavioural variant frontotemporal dementia (bvFTD) is characterized by
      behavioural and social cognitive disturbances, while various psychiatric and
      neurodegenerative disorders may have similar clinical symptoms. Since
      neurodegenerative disorders are eventually progressive, whereas primary
      psychiatric disorders are not, this study aimed to investigate whether the change
      in clinical symptoms over time differed between groups and which biomarkers
      predicted rate of decline. Disease trajectories (median follow-up = 3 years) of
      frontal and stereotyped behaviour, general and frontal cognitive functioning, and
      social cognition were examined in bvFTD (n = 34), other neurodegenerative (n =
      28) and primary psychiatric disorders (n = 43), all presenting with late-onset
      frontal lobe syndrome (45-75 years), using linear mixed models. To gain more
      insight in underlying pathological processes driving disease progression, we
      studied the association of baseline cerebrospinal fluid (CSF) (neurofilament
      light (NfL) and YKL-40 levels, phosphotau181 to total tau ratio) and neuroimaging
      markers with disease trajectories. Frontal behavioural symptoms (e.g.,
      disinhibition, apathy) worsened over time in bvFTD, whereas they improved in
      psychiatric disorders and remained stable in other neurodegenerative disorders.
      General and frontal cognitive decline was observed in bvFTD and other
      neurodegenerative disorders, but not in psychiatric disorders. None of the groups
      showed change in stereotypy and social cognition. For all diagnostic groups,
      higher CSF NfL levels were associated with faster frontal cognitive decline. A
      modest association was observed between caudate volume and stereotyped behaviour.
      Tracking frontal behavioural symptoms and cognition has potential to distinguish
      bvFTD from other disorders. CSF NfL levels seem to be associated with decline in
      frontal cognitive functioning.

PMID- 30103066
TI  - Epigenome-wide association study of suicide attempt in schizophrenia.
AB  - Schizophrenia is a major clinical problem and represents a major risk factor for
      suicide. The molecular mechanisms of suicidal behavior in psychosis remain poorly
      investigated, although it has been hypothesized that epigenetic processes are
      involved in the etiology of both psychosis and suicidality. In this study,
      epigenome-wide patterns of methylation were measured in schizophrenia suicide
      attempters (n = 54) and schizophrenia non-suicide attempters (n = 69) using DNA
      extracted from white blood cells (WBC). Analyses focused on identifying
      differentially methylated CpG sites and gene regions between the attempters and
      non-attempters. We identified the CpG site cg19647197 within the CCDC53 gene,
      which is characterized by hypomethylation of WBC in the attempters compared to
      the non-attempters. Our results suggest that there is variation in DNA
      methylation associated with suicide attempt that may offer novel highlights into
      the molecular mechanisms linked to suicide attempt associated with schizophrenia.

PMID- 30103067
TI  - Negative affect is more strongly associated with suicidal thinking among suicidal
      patients with borderline personality disorder than those without.
AB  - Patients suffering from borderline personality disorder (BPD) are at elevated
      risk for suicidal thoughts and behaviors (STBs), but this well-described and
      clinically important association is not well-understood. Prior research suggests
      that STBs often function as an attempt to escape aversive affect, and that people
      with BPD experience stronger emotion reactivity and greater discomfort with
      emotion than those without BPD. Here, we tested whether negative affective states
      are more likely to predict suicidal thoughts among those with BPD than those
      without this disorder. Data on affective states and suicidal thoughts were
      collected several times per day from 35 psychiatric inpatients using their
      smartphones to capture real-time associations between negative affect and
      suicidal thoughts. Results revealed that the association between negative
      affective states (e.g., abandonment, desperation, guilt, hopelessness,
      loneliness, rage, self-hatred, and upset), and severity of suicidal thinking was
      stronger among those with BPD than among those without BPD. This finding has
      implications for risk assessment and intervention in the clinical setting: for a
      given degree of reported negative affect, patients with BPD experience more
      suicidal ideation than those without. Further research needs to be done to
      elucidate the mechanism of this effect.

PMID- 30103068
TI  - Integrated profiling of phenotype and blood transcriptome for stress
      vulnerability and depression.
AB  - Etiology of depression and its vulnerability remains elusive. Using a latent
      profile analysis on dimensional personality traits, we previously identified 3
      different phenotypes in the general population, namely stress-resilient, 
      vulnerable, and -resistant groups. Here we performed microarray-based blood gene
      expression profiling of these 3 groups (n = 20 for each group) in order to
      identify genes involved in stress vulnerability as it relates to the risk of
      depression. Identified differentially expressed genes among the groups were most
      markedly enriched in ribosome-related pathways. These ribosomal genes, which
      included ribosomal protein L17 (RPL17) and ribosomal protein L34 (RPL34), were
      upregulated in relation to the stress vulnerability. Protein-protein interaction
      and correlational co-expression analyses of the differentially expressed
      genes/non-coding RNAs consistently showed that functional networks involving
      ribosomes were affected. The significant upregulation of RPL17 and RPL34 was also
      observed in depressed patients compared to healthy controls, as confirmed in 2
      independent case-control datasets by using pooled microarray data and qPCR
      experiments (total number of subjects was 122 and 166, respectively). Moreover,
      the upregulation of RPL17 and RPL34 was most marked in DSM-IV major depressive
      disorder, followed by in bipolar disorder, and then in schizophrenia, suggesting
      some diagnostic specificity of these markers as well as their general roles in
      stress vulnerability. These results suggest that ribosomal genes, particularly
      RPL17 and RPL34, can play integral roles in stress vulnerability and depression
      across nonclinical and clinical conditions. This study presents an opportunity to
      understand how multiple psychological traits and underlying molecular mechanisms
      interact to render individuals vulnerable to depression.

PMID- 30103070
TI  - Clinical presentation of ventricular-Hisian and ventricular-nodal accessory
      pathways.
AB  - BACKGROUND: Narrow QRS tachycardia or premature beat with bystander atrial
      activation or ventricular-atrial dissociation is an unusual arrhythmia that can
      present diagnostic and therapeutic challenges. When ventricular-atrial conduction
      is robust, these arrhythmias can be difficult to distinguish from
      atrioventricular nodal reentry. OBJECTIVE: The purpose of this study was to
      describe the electrophysiology characteristics, diagnostic maneuvers, and
      treatment of these types of arrhythmias in a series of 7 cases. METHODS: Standard
      multipolar recording and pacing electrodes were used during electrophysiology
      studies. Catheter ablation was performed using radiofrequency or cryoenergy.
      RESULTS: During electrophysiology studies, ventricular-nodal or ventricular
      Hisian conducting pathways were demonstrated to be responsible for the
      arrhythmias in all 7 cases. Successful ablation of these pathways using
      radiofrequency energy was accomplished in 6 of the 7 cases. CONCLUSION:
      Ventricular-Hisian and ventricular-nodal associated tachyarrhythmias should be
      distinguished from typical forms of atrioventricular nodal reentrant tachycardia.
      Catheter ablation of these pathways can be successfully accomplished using
      mapping techniques described in our report.

PMID- 30103069
TI  - Efficacy of the Unified Protocol for transdiagnostic treatment of comorbid
      psychopathology accompanying emotional disorders compared to treatments targeting
      single disorders.
AB  - OBJECTIVE: This study aimed to examine whether the Unified Protocol (UP), a
      transdiagnostic cognitive-behavioral therapy for emotional disorders (i.e.,
      anxiety, mood, and related disorders), is efficacious in the treatment of co
      occurring emotional disorders compared to established single disorder protocols
      (SDPs) that target specific disorders (e.g., panic disorder). METHOD:
      Participants included 179 adults seeking outpatient psychotherapy. Participant
      age ranged from 18 to 66 years, with an average of 30.66 years (SD = 10.77). The
      sample was 55% female and mostly Caucasian (83%). Diagnostic assessments were
      completed with the Anxiety Disorder Interview Schedule (ADIS), and disorder
      specific, clinician-rated measures for the comorbid diagnoses of interest.
      RESULTS: In both treatment conditions, participants' mean number of diagnoses
      dropped significantly from baseline to posttreatment, and baseline to 12-month
      follow-up. Additionally, large effects were observed for changes in comorbid
      generalized anxiety (ESSG: UP = -1.72; SDP = -1.98), social anxiety (ESSG: UP = 
      1.33, -0.86; SDP = -1.60, -1.54), and depression (ESSG: UP = -0.83; SDP = -0.84).
      Significant differences were not observed in between-group comparisons.
      CONCLUSIONS: Results suggest that both the UP and SDPs are efficacious in
      reducing symptoms of comorbid emotional disorders. The clinical, practical, and
      cost-effective advantages of transdiagnostic CBT are discussed.

PMID- 30103071
TI  - Updated performance of the Micra transcatheter pacemaker in the real-world
      setting: A comparison to the investigational study and a transvenous historical
      control.
AB  - BACKGROUND: Early results of the Micra Investigational Device Exemption (IDE)
      study and Micra Post-Approval Registry (PAR) demonstrated excellent safety and
      efficacy performance; however, intermediate-term results across a large patient
      population in the real-world setting have not been evaluated. OBJECTIVES: We
      report updated performance of the Micra transcatheter pacemaker from a worldwide
      PAR and compare it with the IDE study as well as a transvenous historical
      control. METHODS: The safety objective of the analysis was system- or procedure
      related major complications through 12 months postimplantation. We compared the
      major complication rate with that of the 726 patients from the IDE and with a
      reference data set of 2667 patients with transvenous pacemakers by using a Fine
      Gray competing risk model. RESULTS: The Micra device was successfully implanted
      in 1801 of 1817 patients (99.1%). The mean follow-up period was 6.8 +/- 6.9
      months. Through 12 months, the major complication rate was 2.7% (95% confidence
      interval [CI] 2.0%-3.7%). The risk of major complications for Micra PAR patients
      was 63% lower than that for patients with transvenous pacemakers through 12
      months postimplantation (hazard ratio 0.37; 95% CI 0.27-0.52; P < .001). The
      major complication rate trended lower in the PAR than in the IDE study (hazard
      ratio 0.71; 95% CI 0.44-1.1; P = .160), driven by the lower pericardial effusion
      rate in the PAR. There were 3 cases of infection associated with the procedure,
      but none required device removal and there were no battery or telemetry issues.
      Pacing thresholds were low and stable through 12 months postimplantation.
      CONCLUSION: Performance of the Micra transcatheter pacemaker in international
      clinical practice remains consistent with previously reported data. Major
      complications were infrequent and occurred 63% less often compared to transvenous
      systems. CLINICAL TRIAL REGISTRATION: Micra Transcatheter Pacing System Post
      Approval Registry ClinicalTrials.gov identifier: NCT02536118; Micra Transcatheter
      Pacing Study ClinicalTrials.gov identifier: NCT02004873.

PMID- 30103072
TI  - Integrated analysis of the prognostic role of the lymph node ratio in node
      positive gastric cancer: A meta-analysis.
AB  - BACKGROUND: The lymph node ratio (LNR) as a prognostic parameter for gastric
      cancer has yet to be fully validated in the current tumor node metastasis staging
      system. We assessed the prognostic role of LNR in lymph node-positive gastric
      cancer through a meta-analysis. MATERIALS AND METHODS: PubMed and EMBASE were
      searched for relevant studies up until December 2016. The effect measure for meta
      analysis of primary outcomes was the hazard ratio (HR) for overall survival.
      Pooled HRs and 95% confidence intervals were calculated using random effects
      models. The I2 statistic was used to measure heterogeneity. Subgroup analysis and
      meta-regression were chosen to illustrate the potential heterogeneity of the risk
      factors of outcomes. Publication bias was assessed using Egger's test and Begg's
      funnel plots. Sensitivity analysis was applied to evaluate the origin of the
      heterogeneity. RESULTS: We included 27 studies in this meta-analysis. Higher LNRs
      were significantly associated with a shorter overall survival (OS). High
      heterogeneity among the studies was identified (I2 = 85.6), and the publication
      bias was moderate. Subgroup analysis showed similar results, and elevated LNR was
      associated with late-stage gastric cancer and indicative of a worse prognosis.
      Univariate meta-regression analysis of OS indicated that both treatment type and
      ethnicity may be causes of heterogeneity in patients with gastric cancer (p
      values were 0.005 and 0.008, respectively). CONCLUSION: LNR was associated with a
      significantly poorer OS and LNR was an independent predictor of survival in
      patients with gastric cancer. LNR should be added as one of the parameters to be
      used in future tumor staging classification systems.

PMID- 30103073
TI  - Potential of mesenchymal stromal cells for improving islet transplantation
      outcomes.
AB  - Allogeneic islet transplantation as a therapy for Type 1 Diabetes (T1D) is
      restricted by the limited availability of donor islets, loss of functional islets
      during pre-transplantation culture in vitro and further extensive loss during the
      immediate post-transplantation period when islet function and survival is
      compromised by the hypoxic, inflammatory host environment. In the longer term
      pathogenic T cell responses drive autoimmunity and chronic allograft rejection.
      Experimental studies have demonstrated that mesenchymal stromal cells (MSCs) have
      significant potential to improve the outcomes of clinical islet transplantation.
      This review explores the potential for MSCs and their 'secretome' to influence
      donor islet cell function and survival, as well as the host niche. We discuss the
      possibility of harnessing the therapeutic benefits of MSCs in a cell-free
      strategy to offer a well-defined, cell-free approach to improve the outcomes of
      clinical islet transplantation.

PMID- 30103074
TI  - Factors influencing adherence to continuous positive airway pressure treatment in
      obstructive sleep apnea and mortality associated with treatment failure - a
      national registry-based cohort study.
AB  - OBJECTIVES: Adherence to continuous positive airway pressure (CPAP) in patients
      with obstructive sleep apnea (OSA) is crucial. Our aim was to identify protective
      and risk factors against the discontinuation of CPAP treatment in patients with
      OSA and to estimate the mortality risk in those who were non-adherent to CPAP
      therapy. METHODS: This was a registry-based cohort study from 37 centers across
      Sweden with OSA patients on CPAP in the Swedevox Swedish national registry
      between July 2010 and March 2017. RESULTS: In 16,425 patients (70.8% men) with
      complete follow-up data after 1.2 +/- 0.8 years the adjusted relative risk ratio
      (aRRR) for the discontinuation of CPAP was 0.57 (95% confidence interval (CI)
      0.50-0.65) for use of humidifier, 0.87 (95% CI 0.82-0.92) for increasing age per
      10 years, 0.80 (95% CI 0.77-0.83) for increasing apnea hypopnea index (AHI) per 5
      units/hour, and 0.96 (95% CI 0.95-0.97) per increased unit on the Epworth
      Sleepiness Scale (ESS). Increasing BMI was associated with increased adherence up
      to BMI 35. Women and patients with hypertension ran an increased risk of
      discontinuing CPAP treatment, aRRR 1.28 (95% CI 1.12-1.46) and 1.24 (95% CI 1.12
      1.42) respectively. The adjusted hazard ratio (HR) for mortality was 1.74 (95% CI
      1.32-2.28) among those who did not adhere to CPAP (median follow-up period 2.4
      years after the one year adherence evaluation). CONCLUSION: Use of humidifier is
      associated with greater adherence to CPAP treatment. Other factors predicting
      adherence are increasing age, more severe OSA and overweight up to BMI 35,
      whereas female gender and coexisting hypertension are risk factors for
      discontinuation of CPAP. Failure to adhere to CPAP is associated with increased
      mortality.

PMID- 30103075
TI  - Building a knowledge base: Predicting self-derivation through integration in 6-
      to 10-year-olds.
AB  - Self-derivation of new factual knowledge through integration of separate episodes
      of learning is one means by which children build knowledge. Content generated in
      this manner becomes incorporated into the knowledge base and is retained over
      time; successful self-derivation predicts academic achievement. Yet the component
      processes on which self-derivation through integration depends are as yet
      unknown. In parallel studies with 6- and 8-year-olds (N = 41; Experiment 1) and 8
      and 10-year-olds (N = 40; Experiment 2), we tested a number of predictors
      related to other productive processes and learning (reasoning, executive
      functions, verbal comprehension, and long-term retrieval). Across studies, with
      different methods, only verbal comprehension, a measure of accumulated semantic
      knowledge, accounted for unique variance in self-derivation through integration
      performance. The results indicate that self-derivation through integration of
      separate episodes relates to accumulation of knowledge and the ability to recruit
      the knowledge in the service of specific task demands. Implications for cognitive
      training and transfer are discussed.

PMID- 30103076
TI  - A three-dimensional geometric quantification of human cortical canals using an
      innovative method with micro-computed tomographic data.
AB  - The complex architecture of bone has been investigated for several decades. Some
      pioneer works proved an existing link between microstructure and external
      mechanical loading applied on bone. Due to sinuous network of canals and
      limitations of experimental acquisition technique, there has been little
      quantitative analysis of three-dimensional description of cortical network. The
      aim of this study is to provide an algorithmic process, using Python 3.5, in
      order to identify 3D geometrical characteristics of voids considered as canals.
      This script is based on micro-computed tomographic slices of two bone samples
      harvested from the humerus and femur of male cadaveric subject. Slice images are
      obtained from 2.94 MUm isotropic resolution. This study provides a generic method
      of image processing which considers beam hardening artefact so as to avoid
      heuristic choice of global threshold value. The novelty of this work is the
      quantification of numerous three-dimensional canals features, such as orientation
      or canal length, but also connectivity features, such as opening angle, and the
      accurate definition of canals as voids which ranges from connectivity to possibly
      another intersection. The script was applied to one humeral and one femoral
      samples in order to analyse the difference in architecture between bearing and
      non-bearing cortical bones. This preliminary study reveals that the femoral
      specimen is more porous than the humeral one whereas the canal network is denser
      and more connected.

PMID- 30103078
TI  - Diagnostic meaning of blood p-cresol concentration in forensic autopsy cases.
AB  - In some forensic autopsy cases there are high concentrations of p-cresol in the
      blood. In vivo, p-cresol is the only isomer yielded by intestinal bacteria and is
      excreted into urine. We investigated the diagnostic meaning of p-cresol in the
      blood of forensic autopsy cases. Blood samples from 110 autopsy cases within 48 h
      of the postmortem interval (PMI) and 10 healthy adults were examined. Blood with
      p-cresol-d8 as an internal standard was analyzed using a GC-MS/MS method. Using
      acid and heat deproteinization, free (F) and conjugated (non-protein bound: C;
      protein bound: PC) p-cresol were individually analyzed. The p-cresol
      concentrations were 1.39 +/- 0.86 ug/ml [mean +/- SD] and 1.18 (0.19-18.80) ug/ml
      [median (range)] in healthy adults and autopsy cases, respectively. The p-cresol
      showed no significant relationship to age, sex, fasting duration, survival
      duration, or PMI. No significant differences were found between causes of death.
      Significantly higher levels of C p-cresol were found in cases with
      atherosclerosis in the basilar or renal arteries, or stenosis in the coronary
      artery. Significantly higher levels of p-cresol except F were found in cases with
      hyalinosis of the kidney. Cases with low BMI also showed significantly higher p
      cresol concentrations. The 22 cases of abnormally high total p-cresol were
      investigated. It was considered that high concentrations of p-cresol could be an
      indicator of certain diseases and physical conditions that effect the production,
      absorption, metabolism, circulation, and excretion of p-cresol. Measuring the
      levels of p-cresol may provide valuable information about the antemortem physical
      conditions.

PMID- 30103077
TI  - Advancement of Near-infrared (NIR) laser interceded surface enactment of proline
      functionalized graphene oxide with silver nanoparticles for proficient
      antibacterial, antifungal and wound recuperating therapy in nursing care in
      hospitals.
AB  - Medication obstruction of microscopic organisms has turned into a worldwide
      medical issue, as it makes the ordinary anti-toxins less effective. It is
      desperately expected to investigate novel antibacterial materials and create
      viable treatment techniques to defeat the medication obstruction of anti
      infection agents. Herein, we effectively fabricated silver nanoparticles improved
      proline/graphene oxide nano-flakes (GO-Pro/n-Ag) as novel anti-pathogenic
      substance through simplistic technique. The property of the silver nanoparticles
      activated discharge gave amazing antibacterial and antifungal movement against
      the pathogenic microorganism. Upon supply of NIR, the graphene oxide based
      biomaterials privately increased the temperature, bringing about the high
      mortality of pathogenic microorganism. The GO-Pro biocomposite activated n-Ag
      particles discharging approach for antibacterial, antifungal enables n-Ag to be
      ensured by proline layout without influencing normal cells. The biocomposites
      provided antibacterial and antifungal movement against S. aureus, P.aeruginosa,
      C. albicans and S. cerevisia. Also, the L929 mouse fibroblast cells were utilized
      for cytocompatibility assessment, and the GO-Pro/n-Ag demonstrated low lethality.
      Likewise, the GO-Pro/n-Ag and GO-Pro/n-Ag + NIR are set up for in vivo tests and
      demonstrate incredible antibacterial property in wound model. As the fabricated
      GO-Pro/n-Ag biocomposite nano-flakes have the benefits of minimal effort and high
      anti-pathogenic activity, they may be of promising and helpful antibacterial and
      antifungal specialists for various biomedical applications.

PMID- 30103079
TI  - The effect of older-person centered and integrated health management model on
      multiple lifestyle behaviors: A randomized controlled trial from China.
AB  - OBJECTIVE: To investigate the effectiveness of the older-centered Integrated
      Health Management Model Project (OPCHMP) for multiple lifestyle behaviours in the
      elderly. METHODS: A 2-arm, parallel, randomized controlled trial was conducted in
      Nanjing. The elderly were recruited from multiple community health service
      centres. The intervention group was intervened and received a personalized, 2
      year OPCHMP. The control group only received usual care. Adherence to healthy
      lifestyle behaviours (ATHLBS) is the primary outcome, obtained through a self
      reported composite health behaviour score. The secondary outcomes were health
      indicators. General estimating equation models were performed to analyse
      longitudinal dichotomous data and continuous data. RESULTS: 637 (intervention =
      323; control = 314) participants were included in the study. The participants
      mean age was 70.53 +/- 6.07 years. Significant ATHLBS correction was achieved
      after 24-month follow-up in the intervention group, comparing to controls. And
      the intervention group reported significantly better health indicators.
      CONCLUSION: OPCHMP had positive effect on multiple lifestyle habits in elderly
      population, which is very encouraging.

PMID- 30103080
TI  - Impact of pre-slaughter transport conditions on stress response, carcass traits,
      and meat quality in growing rabbits.
AB  - In growing rabbits (n = 320; 84 d of age), an increase in the journey duration to
      the slaughterhouse from 1 h to 3 h under mild climatic conditions (10-13  degrees
      C; 75-90% relative humidity) affected several stress indicators in the plasma and
      muscle collected at slaughter (cortisol; corticosterone; lactate dehydrogenase,
      LDH; lactate; heat shock protein 70 kDa, HSP70; osmolality, and Na) (0.001 < P <
      .05), reduced muscle L*, b* (P < .01), and meat shear force (P < .05), and
      increased the dressing out percentage and muscle pH (P < .01). An increase in the
      lairage duration before slaughtering from 30 min to 3 h affected muscle cortisol
      and plasma creatinine kinase, LDH, lactate, and HSP70 (0.001 < P < .05),
      increased dressing out percentage and muscle pH (P < .05), but decreased meat
      shear force (P < .001). The interaction between journey and lairage duration was
      significant for several stress indicators and meat quality.

PMID- 30103081
TI  - How do human values influence the beef preferences of consumer segments regarding
      animal welfare and environmentally friendly production?
AB  - Animal welfare and environmental impacts have been emphasized in the sustainable
      production of livestock. Labels are useful tools for clearly providing such
      attribute information to consumers. The aim of this study was to evaluate how
      human values influence consumer segments for beef with information on animal
      welfare and environmentally friendly production. Using a choice experiment, we
      examined whether animal welfare and environmentally friendly labels, country of
      origin and price impact consumer choice. As results, five heterogeneous consumer
      classes were identified using a latent class model: label conscious, domestic
      beef preferring, price conscious, animal welfare preferring and not interested in
      production method. Almost 90% of consumers were interested in and willing to pay
      for beef with animal welfare or environmentally friendly label. The classes with
      significant preferences for such labeled beef were affected by "openness to
      change", "self-enhancement" and "security". Improving consumer attitudes and
      strengthening consumer perception towards labeled beef by marketers and policy
      makers will be required.

PMID- 30103082
TI  - Efficacy of vaginal therapies alternative to vaginal estrogens on sexual function
      and orgasm of menopausal women: A systematic review and meta-analysis of
      randomized controlled trials.
AB  - Genitourinary syndrome of menopause (GSM) increases the probability of female
      sexual dysfunction (FSD). The aim of the current study is to systematically
      assess data regarding sexual function and use of vaginal therapies, alternative
      to vaginal estrogens (VE), in menopausal women with GSM. PubMed, Scopus and
      Cochrane Library were searched (May-September 2017) using combination keywords:
      "dyspareunia and vaginal therapy", "sexual function and vaginal therapy", "orgasm
      and vaginal therapy", "vaginal atrophy" and "genitourinary syndrome of
      menopause". Eligible studies were RCTs focusing on the use of vaginal therapies,
      alternative to VE, in menopausal women. These studies were written in English
      language and published in peer-reviewed journals with impact factor. Assessment
      of risk of bias was performed using the Cochrane Risk of Bias Tool. Outcomes
      involved dyspareunia, vaginal dryness, orgasm and all parameters of sexual
      function. Twenty-nine RCTs including 3689 menopausal women, were included.
      Vaginal therapies, alternative to VE included non-hormonal (vaginal laser,
      lubricants/moisturizers, phytoestrogens and lidocaine) and hormonal ones
      (Dehyadroapiandrosterone (DHEA), testosterone and oxytocin). Dyspareunia and/or
      vaginal dryness were assessed in 72% of the articles, while the FSD and orgasm in
      45% and 28% of articles, respectively. Dyspareunia and vaginal dryness improved
      in all relevant studies. Sexuality scores of lubricants were inferior to
      estrogens [3 studies, n = 138, standardized mean difference (smd) -0.64, (95%CI 
      1.1, -0.2)]. Orgasm domain was the same for the DHEA 0.5% and placebo (2 studies,
      n = 663, smd 1.29 (95% -0.47, 3.05), I2:90%). Sexual satisfaction and sexuality
      score were the same when testosterone was compared or added to estrogen therapy
      (2 studies, n = 99, smd 0.16 (95%CI-0.23,0.56), I2:12% and 2 studies (n = 87),
      smd 0.20 (95%CI-0.23,0.62), I2:0%, respectively. Available data are not adequate
      to provide counseling by the physicians in menopausal women regarding the
      efficacy of vaginal therapies as an alternative to estrogens, on all parameters
      of sexual function.

PMID- 30103083
TI  - A novel mutation of dystrophin in a Becker muscular dystrophy family with severe
      cardiac involvement: from genetics to clinicopathology.
AB  - BACKGROUND: Dystrophin gene defects are the pathogenic molecular basis of Becker
      muscular dystrophy (BMD), characterised by skeletal myopathy and cardiomyopathy.
      Because of the broad phenotype spectrum, it was difficult to use the traditional
      diagnostic method to achieve an early accurate diagnosis of BMD-associated
      cardiomyopathy. METHODS: We applied an in-house gene panel testing and a gene
      filtering strategy to investigate the genetic defect in a four-generation family
      with 73 members. The proband had a heart transplant due to heart failure; the
      explanted heart was subjected to a careful pathological analysis. RESULTS: A
      novel small in-frame mutation (c.4998_5000 del CAG, p.1667 del Ala) of the
      dystrophin gene was identified and co-segregated in the affected family members.
      By using the image segmentation technology, we found the left ventricular free
      wall demonstrated severe fibrofatty replacement of cardiac myocytes from the
      epicardium to the endocardium. CONCLUSION: We identified a novel dystrophin
      mutation (p.1667 del Ala), resulting in BMD-associated cardiomyopathy that
      demonstrated the pathological features of significant fibrofatty replacement in
      the sub-epicardial layer of the ventricle; further, the high-throughput
      sequencing is helpful for making an early diagnosis of BMD.

PMID- 30103084
TI  - Observation of proximities between spin-1/2 and quadrupolar nuclei in solids:
      Improved robustness to chemical shielding using adiabatic symmetry-based
      recoupling.
AB  - We introduce a novel heteronuclear dipolar recoupling based on the R21-1
      symmetry, which uses the tanh/tan (tt) shaped pulse as a basic inversion element
      and is denoted R21-1(tt). Using first-order average Hamiltonian theory, we show
      that this sequence is non-gamma-encoded and that it reintroduces the |m| = 1
      spatial component of the Chemical Shift Anisotropy (CSA) of the irradiated
      isotope and its heteronuclear dipolar interactions. Using numerical simulations
      and one-dimensional (1D) 27Al-{31P} through-space D-HMQC (Dipolar Heteronuclear
      Multiple-Quantum Correlation) experiments on VPI-5, we compare the performances
      of this recoupling to those of other non-gamma-encoded |m| = 1 heteronuclear
      recoupling schemes: REDOR (Rotational-Echo DOuble Resonance), SFAM (Simultaneous
      Frequency and Amplitude Modulation) and R42-1(tt). Such comparison indicates that
      the R21-1(tt) scheme is more robust to CSA, offset and radiofrequency field
      inhomogeneities than the other schemes. We take advantage of the high robustness
      of R21-1(tt) to CSA and offset to demonstrate the possibility to correlate the
      signals of 207Pb isotope with those of neighboring half-integer spin quadrupolar
      nuclei. Such approach is demonstrated experimentally by acquiring 11B-{207Pb} D
      HMQC 2D spectra of Pb4O(BO3)2 crystalline powder.

PMID- 30103085
TI  - A "reactive" turn-on fluorescence probe for hypochlorous acid and its bioimaging
      application.
AB  - An aza-BODIPY-CNOH probe attached aldoxime group demonstrated the specific
      detection for hypochlorous acid by the turn-on red emission signal. NMR and HRMS
      experiments confirmed that the fluorescence originated from the oxidation
      degradation of the non-fluorescence, aldoxime-based aza-BODIPY-CNOH probe into
      the red-fluorescence, nitrile oxide-based aza-BODIPY compound aza-BODIPY-CNO. The
      aza-BODIPY-CNOH probe showed good biocompatibility and was low toxic to living
      cells as shown from MTT experiments. Living RAW264.7 cells imaging indicated the
      aza-BODIPY-CNOH probe had good permeability and either exogenous or endogenous
      HClO caused the intracellular bright-red fluorescence, showing its potential
      hypochlorous acid-specific sensing ability in biological systems.

PMID- 30103086
TI  - The water use dynamics of canola cultivars grown under elevated CO2 are linked to
      their leaf area development.
AB  - The 'CO2 fertilisation effect' is often predicted to be greater under drier than
      wetter conditions, mainly due to hypothesised early season water savings under
      elevated [CO2] (e[CO2]). However, water savings largely depend on the balance
      between CO2-induced improvement of leaf-level water use efficiency and CO2
      stimulation of transpiring leaf area. The dynamics of water use during the
      growing season can therefore vary depending on leaf area development. Two canola
      (Brassica napus L.) cultivars of contrasting growth and vigour (vigorous hybrid
      cv. Hyola 50 and non-hybrid cv. Thumper) were grown under ambient [CO2] (a[CO2],
      ~400 MUmol mol-1) or e[CO2] (~700 MUmol mol-1) with two water treatments (well
      watered and mild drought) in a glasshouse to investigate the interdependence of
      leaf area development and water use. Dynamics of water use during the growing
      season varied depending on [CO2] and cultivars. Early stimulation of leaf growth
      under e[CO2], which also depended on cultivar, overcompensated for the effect of
      increased leaf-level water use efficiency, so that weekly water use was greater
      and water depletion from soil greater under e[CO2] than a[CO2]. This result shows
      that the balance between leaf area and water use efficiency stimulation by e[CO2]
      can tip towards early depletion of available soil water, so that e[CO2] does not
      lead to water savings, and the 'CO2 fertilisation effect' is not greater under
      drier conditions.

PMID- 30103087
TI  - Impact of indoor air quality on respiratory health: results of a local survey on
      housing environment.
AB  - OBJECTIVES: The 'Mon habitat: plus qu'un simple toit' (MHPQST) survey was
      designed to identify public health risks and priorities for local decision makers
      in relation to housing. The aims of the present study were to describe the
      exposure of households to indoor air contaminants and to verify the relationship
      between these contaminants and respiratory symptoms/diseases. STUDY DESIGN: This
      is a cross-sectional study. METHODS: MHPQST was conducted in Baie-Saint-Paul, a
      French Canadian municipality (7000 inhabitants) using a protocol adapted from the
      'Large Analysis and Review of European Housing and Health Status' study performed
      in Europe in 2002-2003. Households were selected from two sectors (less favorable
      and more favorable). Data collection was achieved using three tools (two
      questionnaires and one inspection grid). Indoor air variables were analyzed in
      relation to respiratory symptoms/diseases using logistic regression models
      adjusted for age, gender, income, smoking status, and proximity. RESULTS: A total
      of 161 dwellings (294 inhabitants) participated in the survey. Presence of mold
      on walls, ceilings, or floors was detected by the investigators in 21% of the
      dwellings. Nearly half of the households were in contact with a pet at home and
      12% with environmental tobacco smoke. Exposure to these three determinants was
      significantly associated with certain respiratory symptoms/diseases. CONCLUSION:
      Molds, pets at home, and environmental tobacco smoke are environmental
      determinants that were associated with respiratory health in the present survey.
      These results enabled sensitizing local stakeholders regarding the importance of
      indoor air quality for the respiratory health of their population.

PMID- 30103088
TI  - Gestational weight gain recommendations for Chilean women: a mathematical
      optimization approach.
AB  - OBJECTIVES: We examined if the guidelines for gestational weight gain (GWG)
      proposed by the Institute of Medicine (IOM) are the most suitable for Chilean
      women. STUDY DESIGN: Secondary analysis of records of single full-term births at
      the Dr. Sotero del Rio Hospital, Santiago, Chile, during 2003-2012 (n = 62,579).
      METHODS: From clinical records, we obtained data regarding maternal age, height,
      prepregnancy and at delivery weights, pathologies during pregnancy such as
      gestational diabetes (GDM) and pre-eclampsia, gestational age at delivery, and
      number of infants born small for gestational age (SGA) and large for gestational
      age (LGA). We formulated a mathematical model (MM) to determine the GWG range
      that maximizes the likelihood of a healthy pregnancy (HP) if the recommendation
      is followed. We defined an HP as one where the mother has no complications such
      as pre-eclampsia, GDM, SGA, or LGA. RESULTS: Forty-six percent of women had
      prepregnancy overweight or obesity. The prevalence of GDM, pre-eclampsia, SGA,
      and LGA were 3%, 1.2%, 9%, and 12%, respectively. An HP was present in 76% of
      pregnancies, 79% in the underweight group, 79% in normal weight group, 74% in the
      overweight group, and 67% in obese women. The GWG recommendations given by the MM
      (14-20 kg for underweight, 6-20 kg for normal weight, 9-11 kg for overweight, and
      6-7 kg for obese) led to higher probabilities of achieving an HP than the ones
      obtained with the IOM recommendations. CONCLUSION: The adoption of GWG
      recommendations based on characteristics of the Chilean population might lead to
      better short- and long-term health results for pregnant women.

PMID- 30103089
TI  - The demographic and adaptive history of central African hunter-gatherers and
      farmers.
AB  - Central Africa, a forested region that supports an exceptionally high
      biodiversity, hosts the world's largest group of hunter-gatherers, who live in
      close proximity with groups that have adopted agriculture over the past 5000
      years. Our understanding of the prehistory of these populations has been
      dramatically hampered by the almost total absence of fossil remains in this
      region, a limitation that has recently been circumvented by population genomics
      approaches. Different studies have estimated that ancestors of rainforest hunter
      gatherers and Bantu-speaking farmers separated more than 60 000 years ago,
      supporting the occurrence of ancient population structure in Africa since the
      Late Pleistocene. Conversely, the Holocene in central Africa was characterized by
      large-scale population migrations associated with the emergence of agriculture,
      and increased genetic interactions between autochthonous rainforest hunter
      gatherers and expanding Bantu-speaking farmers. Genomic scans have detected
      numerous candidate loci for positive selection in these populations, including
      convergent adaptation for short stature in groups of rainforest hunter-gatherers
      and local adaptation to endemic malaria in western and central Africans.
      Furthermore, there is recent increasing evidence that adaptive variation has been
      acquired by various African populations through admixture, suggesting a
      previously unappreciated role of intraspecies gene flow in local adaptation.
      Ancient and modern DNA studies will greatly broaden, and probably challenge, our
      view on the past history of central Africa, where introgression from yet
      uncharacterized archaic hominins and long-term adaptation to distinct ecological
      niches are suspected.

PMID- 30103090
TI  - Understanding trends in neighborhood child maltreatment rates: A three-wave panel
      study 1990-2010.
AB  - This study examines how changes in the social and economic structure of
      neighborhoods relate to changes in child maltreatment report rates over an
      extended period. The panel study design allows us to partition the changes in
      child maltreatment report rates into a portion associated with how the levels of
      socio-economic risk factors have changed over time, and a portion related to how
      the relative importance of those factors in explaining maltreatment report rates
      has changed over time. Through the application of fixed effects panel models, the
      analysis is also able to control for unmeasured time-invariant characteristics of
      neighborhoods that may be a source of bias in cross-sectional studies. The study
      finds that increases in vacant housing, single parent families and unemployment
      rates are strongly associated with increases in child maltreatment report rates.
      Changes in racial/ethnic composition did not produce changes in maltreatment
      report rates except when they reached extreme levels of segregation. Although
      poverty rates were predictive of cross-sectional variation in child maltreatment,
      increases in neighborhood poverty became less associated with increases in child
      maltreatment report rates over time.

PMID- 30103091
TI  - Focus on an infrequently used quantity in the context of competing risks: The
      conditional probability function.
AB  - In clinical studies of hematologic and oncologic diseases, the outcomes of
      interest are generally composite time to event endpoints which are usually
      defined by occurrence of different event types. Nonetheless, clinicians are
      interested in studying only one event type, which leads to a competing risks
      situation. In this context, Pepe and Mori presented a quantity directly derived
      from the cumulative incidence: the conditional probability. This function defines
      the probability that a given event occurs, conditionally on not having had a
      competing event by that time. The objective of this paper is to present this
      conditional cumulative incidence function and to compare its use to the
      cumulative incidence in different data sets. Different scenarios highlight the
      importance of the competing event on the interpretation of the conditional
      probability. Conditional probability needs to be interpreted jointly with the
      cumulative incidence. This quantity can be of interest especially when the risk
      of the competing event is large, strongly precludes the risk of the event of
      interest and provides useful additional information.

PMID- 30103092
TI  - Comparison between patients included in randomized controlled trials of ischemic
      heart disease and real-world data. A nationwide study.
AB  - BACKGROUND: The objective was to compare patients with ischemic heart disease
      (IHD) undergoing percutaneous coronary intervention (PCI) who were included in
      randomized controlled trials (RCTs) (trial participants) with patients who were
      not included (nonparticipants) on a trial-by-trial basis and according to
      indication for PCI. METHODS: In this cohort study, we compared patients with IHD
      who were randomized in RCTs in relation to undergoing PCI in Denmark between 2011
      and 2015 were considered as RCT-participants in this study. The RCT-participants
      were compared with contemporary nonparticipants with IHD undergoing PCI in the
      same period, and they were identified using unselected national registry data.
      The primary end point was all-cause mortality. RESULTS: A total of 10,317 (30%)
      patients were included in 10 relevant RCTs (trial participants), and a total of
      23,644 (70%) contemporary patients did not participate (nonparticipants). In all
      the included RCTs, nonparticipants had higher hazard ratios for mortality
      compared to trial participants (P < .001). Among all patients treated with PCI,
      the pooled estimates showed a significantly higher mortality rate for
      nonparticipants compared to trial participants (hazard ratio: 2.03, 95% CI: 1.88
      2.19) (P < .001). When patients were stratified according to indication for PCI,
      the pooled estimates showed a significantly lower mortality rate for trial
      participants compared to nonparticipants in all strata (P for all < .001).
      CONCLUSIONS: Trial participants in recently performed RCTs including patients
      undergoing PCI were not representative of the general population of patients with
      IHD treated with PCI according to clinical characteristics and mortality. The
      difference in mortality was found irrespective of the indication for PCI. Thus,
      results from RCTs including patients undergoing PCI should be extrapolated with
      caution to the general patient population.

PMID- 30103093
TI  - Mismatch tolerance during homologous recombination in mammalian cells.
AB  - We investigated the homology dependency of recombination in thymidine kinase (tk)
      deficient mouse fibroblasts. Cells were transfected with DNA constructs harboring
      a herpes tk gene (the "recipient") rendered non-functional by an oligonucleotide
      containing the recognition site for endonuclease I-SceI. Constructs also
      contained a "donor" tk sequence that could restore function to the recipient gene
      through spontaneous gene conversion or via repair of a double-strand break (DSB)
      at the I-SceI site. Recombination events were recoverable by selection for tk
      positive clones. Three different donors were used containing 16, 25, or 33
      mismatches relative to the recipient. The mismatches were clustered, forming an
      interval of "homeology" relative to the recipient sequences. We show that when
      homeologous sequences were surrounded by high homology, mismatches were
      frequently included in gene conversion events. Notably, conversion tracts from
      spontaneous recombination included either all or none of the mismatches,
      suggesting that recombination must begin and end in high homology. This
      requirement was relaxed for events that occurred near an induced DSB, as a
      significant number of these latter conversion tracts had one end positioned
      within homeology. Knock-down of mismatch repair showed that incorporation of
      mismatches into gene conversion tracts can involve repair of mismatched
      heteroduplex intermediates, indicating that mismatch repair does not necessarily
      impede homeologous genetic exchange. Our results illustrate (1) genetic exchange
      between homeologous sequences in a mammalian genome is enabled by nearby
      homology, (2) proximity to a DSB impacts the homology requirements for where
      genetic exchange may begin and end, and (3) mismatch correction and previously
      documented anti-recombination activity are separable functions of the mismatch
      repair machinery in mammalian cells.

PMID- 30103094
TI  - Adenosquamous carcinoma of the right colon: A case report and review of the
      literature.
AB  - INTRODUCTION: Adenosquamous carcinoma is a rare colorectal tumor with both an
      adenocarcinoma and a squamous cell carcinoma component. To the best of our
      knowledge, only few cases have been reported in the literature. CASE
      PRESENTATION: We report a case of a 46-year-old woman, hospitalized for large
      bowel obstruction syndrome. Computed tomography scan showed an irregular mass of
      the right colic angle, responsible for an occlusive syndrome with distension of
      the right colon, the appendix and the terminal ileum. The patient underwent right
      hemicolectomy with D2 lymphadenectomy. Histopathological examination revealed
      mixed adenocarcinoma and squamous carcinoma. Adjuvant chemotherapy was prescribed
      for the patient. DISCUSSION: Adenosquamous carcinoma is a rare colorectal
      neoplasm revealed by non-specific complaints. Its clinicopathology is not yet
      understood. Preoperative diagnosis is often difficult. Surgical resection remains
      the mainstay of treatment. CONCLUSION: Adenosquamous carcinoma is a malignant
      tumor with poorer prognosis than adenocacinomas.

PMID- 30103095
TI  - Palbociclib enhances radiosensitivity of hepatocellular carcinoma and
      cholangiocarcinoma via inhibiting ataxia telangiectasia-mutated kinase-mediated
      DNA damage response.
AB  - AIM: Palbociclib is an oral cyclin-dependent kinase 4/6 inhibitor, which is
      efficacious in treating breast cancer. Currently, there are numerous active
      clinical trials testing palbociclib alone or in combination with other
      medications for treating various types of malignancies. Here, we evaluated the
      anti-cancer effect of palbociclib in combination with radiation therapy (RT) for
      treating human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) and
      addressed the molecular mechanism behind the combination therapy. METHODS:
      Immunofluorescence staining of gammaH2AX or 53BP1 was used to determine the
      effect of palbociclib on double-strand break (DSB) repair. Clonogenic assays,
      sphere formation and cell death ELISA were performed to study the sensitising
      effect of palbociclib on radiation-induced cytotoxicity. Signal alteration in DSB
      repair pathways was examined by Western blot analysis. Finally, we evaluated the
      in vivo anti-cancer activity and the associated molecular events of the
      combination therapy in a preclinical HCC xenograft model. RESULTS: Palbociclib
      affected the kinetics of DNA repair and enhanced the radiation sensitivity of HCC
      and CCA cells. Importantly, we found that palbociclib inhibits ataxia
      telangiectasia-mutated (ATM) kinase, the key upstream kinase responding to RT
      induced DSBs. Furthermore, we showed that the inhibitory effect of palbociclib on
      RT-induced ATM kinase activation is mediated by protein phosphatase 5 (PP5). Both
      in vitro and in vivo investigations revealed that the inhibition of the PP5-ATM
      axis by palbociclib after DNA damage is responsible for the synergism between
      palbociclib and RT. CONCLUSION: Our findings provide a novel combination strategy
      against liver cancer cells. Clinical trials using palbociclib as an adjuvant in
      RT are warranted.

PMID- 30103096
TI  - Evaluation of health-related quality of life and symptoms in patients with
      advanced non-squamous non-small cell lung cancer treated with nivolumab or
      docetaxel in CheckMate 057.
AB  - BACKGROUND: Nivolumab, a programmed death-1 inhibitor, prolonged overall survival
      and had a favourable safety profile versus docetaxel in previously treated
      patients with advanced non-squamous non-small cell lung cancer (NSCLC) in the
      phase III CheckMate 057 trial. AIM: To evaluate health-related quality of life
      (HRQoL) using patient-reported outcomes. METHODS: Disease-related symptoms and
      general health status were assessed using two validated patient-reported
      instruments, the Lung Cancer Symptom Scale (LCSS) and the European Quality of
      Life Five Dimensions (EQ-5D), respectively. The proportion of patients with
      disease-related symptom improvement at 12 weeks on the LCSS average symptom
      burden index (ASBI) was a secondary end-point. LCSS 3-item global index (3-IGI),
      EQ-5D utility index and EQ-5D visual analogue scale (VAS) scores were also
      determined. Mixed-effects model repeated measures (MMRM) and time to first
      deterioration analyses assessed longitudinal changes. RESULTS: Mean baseline LCSS
      ASBI scores were similar in both arms. By week 12, rates of disease-related
      improvement (95% confidence interval) were similar between nivolumab (17.8% [13.6
      22.7]) and docetaxel (19.7% [15.2-24.7]); however, numerical differences in LCSS
      ASBI mean change from baseline favoured nivolumab. Subsequently, LCSS ASBI scores
      improved with nivolumab and worsened with docetaxel, with statistically
      significant between-arm differences at weeks 12, 24, 30 and 42. HRQoL
      improvements with nivolumab versus docetaxel were also supported by the LCSS 3
      IGI, EQ-5D VAS and MMRM analysis. Time to first HRQoL deterioration was longer
      with nivolumab than with docetaxel. CONCLUSION: Nivolumab improved disease
      related symptoms and overall health status versus docetaxel for second-line
      treatment of advanced non-squamous NSCLC. CLINICAL TRIAL REGISTRATION:
      NCT01673867.

PMID- 30103097
TI  - Pain-related anxiety and smoking processes: The explanatory role of dysphoria.
AB  - Scientific evidence suggests that pain-related anxiety may contribute to the
      maintenance of tobacco addiction among smokers with varying levels of pain. Yet,
      no work has investigated the relation between pain-related anxiety and cognitive
      based smoking processes within an indirect effect model. Dysphoria may explain
      the relation between pain-related anxiety and cigarette smoking, as it is a
      construct that relates to both pain and smoking outcomes. Thus, the current cross
      sectional study examined the indirect effect of pain-related anxiety and three
      clinically significant smoking processes: perceived barriers to cessation,
      negative affect reduction motives, and negative mood abstinence expectancies via
      dysphoria. Participants included 101 (Mage = 32.74 years, SD = 13.60; 35.6%
      female) adult tobacco cigarette smokers with low cigarette dependence. Results
      indicated that pain-related anxiety had an indirect effect on all dependent
      variables through dysphoria. The current findings provide evidence that dysphoria
      may serve to maintain maladaptive smoking processes in smokers who experience
      pain-related anxiety. This study furthers research on pain-smoking relations by
      providing initial evidence for a conceptual model in which smokers with elevated
      pain-related anxiety endorse greater dysphoric symptoms and use smoking to reduce
      or escape symptoms of their pain-related anxiety and dysphoria, thus contributing
      to the maintenance of tobacco dependence.

PMID- 30103098
TI  - Correct knowledge of medical cannabis legal status in one's own state:
      Differences between adolescents and adults in the United States, 2004-2013.
AB  - BACKGROUND: Studies have found age-specific effects of medical cannabis laws
      (MCLs), particularly affecting adult cannabis use but not adolescent use. We
      examined whether age differences in MCL knowledge are in accordance with age
      differences in MCL effects on cannabis use. METHODS: Data from the 2004-2013
      repeated cross-sectional National Surveys on Drug Use and Health included people
      ages 12 and older in the United States. State-aggregated MCL knowledge was the
      proportion of people that correctly identified living in a state that did not
      allow medical cannabis prior to MCL enactment, or that allowed medical cannabis
      after MCL enactment. We regressed state-aggregated MCL knowledge on time-varying
      MCL enactment (i.e., no MCL by 2015, before MCL, after MCL), testing associations
      by age strata (12-17, 18-25, 26+), open dispensary status, and adjusting for time
      and state-level demographics. RESULTS: Model-based MCL knowledge was
      significantly lower among adolescents than adults; after enactment, 36.8% of ages
      12-17, 48.8% of ages 18-25, and 45.4% of ages 26+ were aware of their state's MCL
      status. Correct MCL status knowledge decreased across all age groups after MCL
      enactment (i.e., low knowledge of MCL changes at the time they occurred). Open
      cannabis dispensaries significantly increased correct MCL knowledge, with a 7.7
      point increase for adolescents and a 17.5-point increase for adults 26 + .
      CONCLUSIONS: Lower MCL knowledge among adolescents than adults was in accordance
      with MCL effects on cannabis use previously observed among adults only. Studies
      should assess whether MCL knowledge is a consequence or predictor of individual
      level cannabis use across age groups.

PMID- 30103099
TI  - Influence of on-network, traffic, signal, demographic, and land use
      characteristics by area type on red light violation crashes.
AB  - The focus of this research paper is on extraction of predictor variables
      pertaining to on-network, traffic, signal, demographic, and land use
      characteristics, by area type, and examining their influence on the number of red
      light violation crashes. Data for the city of Charlotte, North Carolina was
      extracted and used for analysis. Three different sets of signalized intersections
      were selected in the three different area types - Central Business District
      (CBD), urban, and suburban areas. Each set is comprised of sixty signalized
      intersections (total 180 signalized intersections). The number of red light
      violation crashes from January 2010 to December 2014, within the vicinity of each
      selected signalized intersection, was considered as the dependent variable to
      develop crash estimation models for each area type. The crash estimation models
      by area type were compared with the crash estimation model developed considering
      all the 180 signalized intersections together. Different predictor variables were
      found to be significant at a 95% confidence level in three different areas. Log
      link model with Negative Binomial distribution was observed to best fit the data
      used in this research. Findings indicate that enforcement, either manually or
      using red light running cameras (RLCs), at signalized intersections with high
      traffic volume in the CBD area; at signalized intersections with high traffic
      volume, high all-red clearance time, near high density of horizontal mixed non
      residential and open space/recreational type land uses in urban area; at
      signalized intersections with high traffic volume, speed limit on the major
      approach, the number of lanes on the minor approach, and all-red clearance time
      and areas surrounded with horizontal mixed non-residential and retail type land
      use in suburban areas, would lead to a reduction in the number of red light
      violation crashes.

PMID- 30103100
TI  - The relationship between driving skill and driving behavior: Psychometric
      adaptation of the Driver Skill Inventory in China.
AB  - Most road accidents are caused by human factors alone or in combination with
      other factors. Deficits in driving skill are a human factor that contributes to
      accidents. It is important to focus on driving skills to reduce traffic accidents
      and enhance safe driving. In this study, we adopted a Chinese version of the
      Driver Skill Inventory (DSI) and explored its correlation with driving behaviors,
      sociodemographic factors and personality. A total of 295 licensed drivers
      voluntarily completed a survey that covered the DSI, the Driver Behavior
      Questionnaire, the Positive Driver Behavior Scale, self-reported traffic
      accidents, penalty points and fines, the Big Five Inventory, and sociodemographic
      parameters. First, the results of principal axis analysis on the DSI yielded two
      clear factors: perceptual-motor skills and safety skills. Second, both perceptual
      motor skills and safety skills were positively correlated with positive
      behaviors. Safety skills were negatively correlated with all aberrant driving
      behaviors (e.g., aggressive violations, ordinary violations, errors, and lapses),
      whereas perceptual-motor skills were negatively correlated with errors and
      lapses. Third, with regard to penalties, safety skills were negatively associated
      with penalty fines and points received within the past year, whereas perceptual
      motor skills showed no such correlation. Fourth, with regard to sociodemographic
      parameters, perceptual-motor skills were positively correlated with years of
      holding a driving license, weekly driving distance and annual driving distance.
      Men reported higher perceptual-motor skills than women, whereas safety skills
      were unrelated to gender. Fifth, structural equation modeling was conducted to
      test the effects of personality traits on driving skill. The results showed that
      conscientiousness, neuroticism and openness to experience were significant
      predictors of perceptual-motor skills, whereas agreeableness and
      conscientiousness were significant predictors of safety skills. Overall, based on
      these results, the Chinese version of the DSI has acceptable internal consistency
      and a stable structure; thus, it represents a useful tool to measure driving
      skill. Moreover, the measurement of personality traits, which are important
      individual factors closely linked to driving skill, can aid in the education of
      professional drivers or to inform preventative and educational activities that
      focus on personality traits in addition to knowledge.

PMID- 30103101
TI  - Selected highlights from clinical anesthesia and pain management.
AB  - STUDY OBJECTIVE: To review research highlights of manuscripts published in 2017
      that pertain to all aspects of the clinical practice of anesthesiology. DESIGN:
      Narrative review. SETTING: N/A. MATERIALS: The major themes addressed in this
      review include recent studies examining airway management, obstetrical and
      gynecological anesthesia, pediatric anesthesia, cardiac anesthesia, regional
      analgesia and pain management. INTERVENTIONS: N/A. MAIN RESULTS: N/A.
      CONCLUSIONS: This review will highlight and inform anesthesiologists of the
      developing trends in clinical anesthesia and will also pose new challenges for
      further studies.

PMID- 30103102
TI  - Conversion of oral endotracheal tube to nasal endotracheal tube without
      laryngoscopy.

PMID- 30103104
TI  - Examining the effects of punishment schedule density on the development and
      maintenance of avoidance and safety behaviours: Implications for exposure
      therapies.
AB  - BACKGROUND AND OBJECTIVES: Engaging in safety behaviors in the absence of actual
      threat is a key feature of many psychological disorders, including OCD and
      depression. Failure to discriminate between threatening and safe environments may
      make these behaviors resistant to change. The purpose of the current study is to
      investigate the conditions under which avoidance and safety behaviors are
      developed and maintained. METHODS: In experiment 1, sixty-seven participants who
      were initially screened for low obsessive-compulsive behavior were invited to
      play a computerized game to gain points and avoid their potential loss. In Phase
      1, they were exposed to a lean punishment schedule (relatively frequent point
      losses) and a dense schedule (highly frequent point losses). In Phase 2, they
      were tested on engagement in safety behaviors, where no punishment had been
      programmed. In experiment 2, twenty-two new participants were exposed to the lean
      punishment schedule followed immediately by the no point loss condition (Phase
      2), one and two weeks after their initial exposure to the punishment conditions
      to test for the maintenance of safety behavior over time. RESULTS: Findings
      demonstrated that participants developed avoidance immediately, but safety
      behavior was developed and maintained only for those who were exposed to the lean
      punishment schedule. LIMITATIONS: Prolonged exposure to dense punishment
      schedules may yield different results because the contrast between safe and
      aversive environments may be less discernible. CONCLUSIONS: These findings are
      important because they provide experimental evidence on the conditions that
      render safety behaviors difficult to amend, and offer important recommendations
      for clinical practice.

PMID- 30103103
TI  - Development of infectious cDNA clones of Grapevine leafroll-associated virus 3
      and analyses of the 5' non-translated region for replication and virion
      formation.
AB  - Infectious cDNA clones were developed for Grapevine leafroll-associated virus 3
      (GLRaV-3, genus Ampelovirus, family Closteroviridae). In vitro RNA transcripts
      generated from cDNA clones showed replication via the production of 3'-coterminal
      subgenomic (sg) mRNAs in Nicotiana benthamiana protoplasts. The detection of
      sgRNAs and the recovery of progeny recombinant virions from N. benthamiana leaves
      agroinfiltrated with full-length cDNA clones confirmed RNA replication and virion
      formation. The 5' non-translated region (5' NTR) of GLRaV-3 was exchangeable
      between genetic variants and complement the corresponding cognate RNA functions
      in trans. Mutational analysis of the 5' NTR in minireplicon cDNA clones showed
      that the conserved 40 nucleotides at the 5'-terminus were indispensable for
      replication, compared to downstream variable portion of the 5' NTR. Some of the
      functional mutations in the 5' NTR were tolerated in full-length cDNA clones and
      produced sgRNAs and virions in N. benthamiana leaves, whereas other mutations
      affected replication and virion formation.

PMID- 30103105
TI  - Three dimensional primary cultures for selecting human breast cancers that are
      sensitive to the anti-tumor activity of ipatasertib or taselisib in combination
      with anti-microtubule cytotoxic drugs.
AB  - Two inhibitors of phosphatidylinositol 3-kinase (PI3K) pathway taselisib,
      targeting the mutant PI3K-subunit-alpha (PI3KA) and ipatasertib, AKT-inhibitor,
      are currently under clinical investigation in breast cancer (BC) patients. We
      have previously demonstrated the anti-tumor efficacy of these anti-PI3K/AKT
      inibitors in combination with anti-microtubule drugs in human BC cell lines,
      through a complete cytoskeleton disorganization. In this work, we generated ex
      vivo three-dimensional (3D) cultures from human BC as a model to test drug
      efficacy and to identify new molecular biomarkers for selection of BC patients
      suitable for anti-PI3K/AKT-inibitors treatment. We have established 3D cultures
      from 25/27 human BC samples, in which the ability of growth in vitro replicates
      the clinical and biological aggressiveness of the original tumors. According to
      the results of next generation sequencing analysis, a direct correlation was
      found between PI3KA mutations and the sensitivity in 3D models in vitro to
      taselisib and ipatasertib alone and combined with anti-microtubule agents.
      Moreover, mutations in HER and MAPK families related genes, including EGFR, KRAS
      and BRAF, were found in resistant samples, suggesting their potential role as
      negative predictive factors of response to these agents. Thus, we demonstrated
      that ex vivo 3D cultures from human BC patients allow a rapid and efficient drug
      screening for chemotherapies and targeted agents in genetically selected patients
      and represent an innovative model to identify new biomarkers of drug resistance.

PMID- 30103106
TI  - Docking and QSAR analysis of tetracyclic oxindole derivatives as alpha
      glucosidase inhibitors.
AB  - The alpha-glucosidase inhibitors are considered as important agents in drug
      discovery against diabetes mellitus. Molecular docking and quantitative structure
      activity relationship (QSAR) were performed based on a series of tetracyclic
      oxindole derivatives to elucidate key structural properties affecting inhibitory
      activity and support the design of new alpha-glucosidase inhibitors. The
      molecular docking results demonstrate that at least two hydrogen bonds between
      Thr681 and Arg676 residues and the oxygen atoms in amid groups have an important
      role in the optimum binding of inhibitors. In addition, the sum of polar contacts
      of Arg699, Arg670, Glu792 and Glu301 residues with the alpha-glucosidase
      inhibitors have more than one third of total binding free energy. The docked
      conformations of the inhibitors with the best binding free energy were used to
      construct QSAR models. As a primary survey and a graphical comparing tool, the
      partial least squares-discriminant analysis (PLS-DA) technique was successfully
      employed to classify active and inactive inhibitors. The validated QSAR analysis
      were performed through genetic algorithm-partial least squares (GA-PLS) and
      support vector machine (SVM) techniques. The QSAR model reveals that important
      features of J3D, Mor26 u and HOMA have a high predictive capability (R2p = 0.837,
      Q2LOO = 0.871, R2LSO = 0.790 and r2m  = 0.758) using GA-PLS/SVM strategy.
      Generally, the suggested QSAR analysis based on classification, docking and GA
      PLS/SVM strategy may help suggest chemical scaffold to design novel oxindole
      derivatives as alpha-glucosidase inhibitors.

PMID- 30103107
TI  - Implications of the replaced right hepatic artery originating from the
      gastroduodenal artery in the setting of a pancreatic head mass.
AB  - PURPOSE: The anatomic variability of the hepatic artery has important
      implications in the treatment of periampullary cancers. The purpose is of this
      report is to describe the importance of the replaced right hepatic artery
      originating from the gastroduodenal artery, which is typically removed during a
      pancreatic head resection, and to demonstrate how this variant can markedly alter
      treatment planning and intraoperative decision making. MATERIALS AND METHODS: In
      this report, two cases of a replaced right hepatic artery originating from the
      gastroduodenal artery are described in the setting of a borderline-resectable
      pancreatic adenocarcinoma identified on preoperative CT imaging. RESULTS: The
      importance of identifying this variant preoperatively is highlighted. In
      addition, the implications involved in preserving the replaced right hepatic
      artery are emphasized, requiring preservation of a portion of the gastroduodenal
      artery within the pancreatic parenchyma during pancreaticoduodenectomy.
      CONCLUSION: The location of this variant in the setting of a pancreatic head
      malignancy mandates its attention by a multidisciplinary team of radiologists,
      radiation oncologists, medical oncologists, and surgeons, prior to
      pancreaticoduodenectomy.

PMID- 30103108
TI  - MRI liver fat quantification in an oncologic population: the added value of
      complex chemical shift-encoded MRI.
AB  - INTRODUCTION: Chemotherapy prolongs the survival of patients with advanced and
      metastatic tumors. Since the liver plays an active role in the metabolism of
      chemotherapy agents, hepatic injury is a common adverse effect. The purpose of
      this study is to compare a novel quantitative chemical shift encoded magnetic
      resonance imaging (CSE-MRI) method with conventional T1-weighted In and Out of
      phase (T1 IOP) MR for evaluating the reproducibility of the methods in an
      oncologic population exposed to chemotherapy. MATERIALS AND METHODS: This
      retrospective study was approved by the institutional review board with a waiver
      for informed consent. The study included patients who underwent chemotherapy, no
      suspected liver iron overload, and underwent upper abdomen MRI. Two radiologists
      independently draw circular ROIsin the liver parenchyma. The fat fraction was
      calculated from IOP imaging and measured from IDEAL-IQ fat fraction maps. Two
      different equations were used to estimate fat with IOP sequences. Intra-class
      correlation coefficient and repeatability coefficient were estimated to evaluate
      agreement between two readers on iron level and fat fraction measurement.
      RESULTS: CSE-MRI showed a higher reliability in fat quantification compared with
      both IOP methods, with a substantially higher inter-reader agreement (0.961 vs
      0.372). This has important clinical implications. CONCLUSION: The novel CSE-MRI
      method described here provides increased reproducibility and confidence in
      diagnosing hepatic steatosis in a oncologic clinical setting. IDEAL-IQ has been
      proved to be more reproducible than conventional IOP imaging.

PMID- 30103109
TI  - Plicae palmatae on MRI in the pediatric population.
AB  - PURPOSE: To examine the presence of ridge of plicae palmatae (RPP) in pediatric
      population and evaluate its depiction rate and appearance on magnetic resonance
      imaging (MRI). MATERIALS AND METHODS: Consecutive pelvic MRI examinations of
      female patients aged 0-19 years between January 2005 and April 2017 were
      retrospectively reviewed. Patients with underlying diseases affecting the uterus
      and whose MRI data were not available on the picture archiving and communication
      system were excluded. Thus, 171 pelvic MRI cases were included (mean patient age,
      11 years). Morphologic appearance of RPP was evaluated. RPP depiction rate was
      evaluated in the following age groups: group A, 0-2 years; B, 3-6 years; C, 7-10
      years; and D, 11-19 years. Pearson Chi square test or Fisher's exact test was
      used to assess statistical significance of differences in RPP visualization
      frequencies between the groups using SPSS for Windows, version 11.0.0.1 J.
      Statistical significance was set at P < 0.05. RESULTS: RPP appeared as a folded
      structure rather than tumorous in all cases. Depiction rate varied according to
      age: group A, 8/21 (38.1%); B, 0/16 (0%); C, 6/24 (25.0%); and D, 62/110 (56.4%).
      Depiction rate in group B was the lowest and significantly lower than those in
      groups A and D. However, RPP was most frequently observed in group D, and was
      significantly more frequent than in groups B and C. CONCLUSION: RPP could be
      observed on MRI in a pediatric population, and careful interpretation is
      necessary in such cases, although no case with tumorous appearance was observed.
      Depiction rate varies according to age, probably reflecting uterine maturity.

PMID- 30103110
TI  - Mechanical performance of Y-TZP monolithic ceramic after grinding and aging:
      Survival estimates and fatigue strength.
AB  - This study aims to evaluate the flexural fatigue strength and survival estimates
      of an Y-TZP monolithic ceramic after grinding and aging. Ceramic discs (1.2 mm
      thickness * 15.0 mm diameter - ISO, 6872, 2015) of zirconia (Zirlux FC2 - Ardent;
      Ivoclar Vivadent) were made and randomly allocated into 6 groups (n = 10),
      according to grinding and aging factors: Ctrl - as-sintered; Ctrl Sto - as
      sintered and dry stored at room temperature for 2 years; Ctrl Aut Sto - as
      sintered, submitted to autoclaved aging (134  degrees C, 2 bar, 20 h) and then
      dry stored for 2 years; and similar conditions for ground samples (Ground; Ground
      Sto; Ground Aut Sto). Grinding was performed with diamond burs (#3101G, KG
      Sorensen) coupled to a contra-angle torque multiplier attached to a low speed
      motor under constant irrigation. Fatigue testing followed a step-stress approach.
      Data from strength and number of cycles until fracture were recorded and analyzed
      through Kaplan-Meier and Mantel-Cox tests. Both grinding and aging increase
      monoclinic phase content. The topography was altered by grinding but not by aging
      procedures. Grinding did not alter the fatigue strength (Ctrl = Ground), while
      aging increase it only for ground groups (Ground Sto, Ground Aut Sto). Aged
      conditions (Ctrl Sto; Ground Sto; Ctrl Aut Sto; Ground Aut Sto) showed increased
      survival probabilities for both flexural fatigue strength and cycles for failure.
      Therefore, despite promoting monoclinic phase increase, aging and grinding did
      not deleteriously affect the fatigue behavior of Y-TZP ceramics.

PMID- 30103111
TI  - Dehydration of individual bovine trabeculae causes transition from ductile to
      quasi-brittle failure mode.
AB  - Trabecular bone is located inside flat bones as well as in the epi- and
      metaphysis of long bones and plays a key role with respect to load transfer.
      Disorders, such as osteoporosis, weaken the structural integrity and may also
      cause changes in the mechanical properties of individual trabeculae, such as
      Young's modulus. Knowledge of mechanical tissue properties are necessary to
      assess risk of bone fracture with finite element analysis (FEA). However, such
      parameters are most often obtained from experiments on air-dried specimens which
      do not reflect the physiological conditions. In this study, micro-tensile tests
      of individual bovine trabeculae were performed until fracture to evaluate the
      influence of hydration state on the elastic and post-yield behavior. Dehydration
      resulted in significantly (p < 0.001) lower post yield work and ultimate strain,
      whereas stiffness, yield stress and ultimate stress were significantly (p <
      0.001) larger. Further, inelastic strain of dehydrated samples was confined to a
      small region, whereas it was distributed over a larger area in wet samples.
      Similarly, microdamage accumulation was confined to a significantly smaller
      region (p < 0.05) in dry samples, compared to wet ones. Thus, damage localization
      resulted in a quasi-brittle failure in dry samples. In contrast, hydrated samples
      showed a much larger area of microdamage accumulation, resulting in a ductile
      failure. These results emphasize the need to keep bone samples hydrated during
      mechanical testing. Sequentially, the findings may help to improve clinical
      applications like FEA-based bone strength predictions.

PMID- 30103112
TI  - How does hydrofluoric acid etching affect the cyclic load-to-failure of lithium
      disilicate restorations?
AB  - This study investigated the effect of etching with distinct hydrofluoric (HF) 
      acid concentrations on the cyclic load-to-failure (CLf) of simplified lithium
      disilicate glass-ceramic restorations adhesively cemented to a dentin analogue (n
      = 20): non-etched/control (CTRL), or etched for 20 s with HF acid at 3% (HF3), 5%
      (HF5), or 10% (HF10). A silane coating was then applied onto the ceramic
      surfaces. Fatigue tests followed the staircase approach (initial load= 720 N;
      step-size= 70 N; 500,000 cycles per sample; 20 Hz) using a hemispheric stainless
      steel piston (O= 40 mm) under water. The CLf data were analyzed using Dixon and
      Mood method. Topographic and fractographic analyses were conducted. CLf (in N) of
      HF3 (1355 +/- 32.0) and HF5 (1335 +/- 58.8) groups were the highest and
      statistically similar; HF10 presented intermediate CLf (1175 +/- 132.9), while
      the non-etched group had the lowest one (965 +/- 145.0). Topographical analysis
      showed that the higher the HF acid concentration, the more pronounced the
      topographical changes. All failures (radial cracks) started from the inner
      surface of the ceramic discs. Topographical changes promoted by intermediate HF
      acid concentrations (3% and 5%) may improve fatigue performance for adhesively
      cemented lithium disilicate restorations.

PMID- 30103113
TI  - Selective laser melted titanium alloys for hip implant applications: Surface
      modification with new method of polymer grafting.
AB  - A significant number of hip replacements (HR) fail permanently despite the
      success of the medical procedure, due to wear and progressive loss of
      osseointegration of implants. An ideal model should consist of materials with a
      high resistance to wear and with good biocompatibility. This study aims to
      develop a new method of grafting the surface of selective laser melted (SLM)
      titanium alloy (Ti-6Al-4V) with poly (2-methacryloyloxyethyl phosphorylcholine)
      (PMPC), to improve the surface properties and biocompatibility of the implant.
      PMPC was grafted onto the SLM fabricated Ti-6Al-4V, applying the following three
      techniques; ultraviolet (UV) irradiation, thermal heating both under normal
      atmosphere and UV irradiation under N2 gas atmosphere. Scanning electron
      microscopy (SEM), 3D optical profiler, energy-dispersive X-ray spectroscopy
      (EDS), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared
      spectroscopy (FTIR) were used to characterise the grafted surface. Results
      demonstrated that a continuous PMPC layer on the Ti-6Al-4V surface was achieved
      using the UV irradiation under N2 gas atmosphere technique, due to the
      elimination of oxygen from the system. As indicated in the results, one of the
      advantages of this technique is the presence of phosphorylcholine, mostly on the
      surface, which reveals the existence of a strong chemical bond between the
      grafted layer (PMPC) and substrate (Ti-6Al-4V). The nano-scratch test revealed
      that the PMPC grafted surface improves the mechanical strength of the surface and
      thus, protects the underlying implant substrate from scratching under high loads.

PMID- 30103114
TI  - miR-23c suppresses tumor growth of human hepatocellular carcinoma by attenuating
      ERBB2IP.
AB  - MicroRNAs (miRNAs) regulate a variety of development and physiologic processes,
      and play prominent roles in the initiation and progression of human cancers
      including hepatocellular carcinoma (HCC). MiR-23c is recently emerging as a
      cancer-associated miRNA, while its expression status and functional role in HCC
      are unrevealed yet. Here, we found that miR-23c underexpression was associated
      with the tumorigenesis of HCC based on TCGA data. qRT-PCR analysis revealed that
      miR-23c expression was reduced in HCC tissues and cell lines. Clinical analysis
      indicated that low miR-23c expression was correlated with large tumor size, high
      tumor grade, advanced tumor stage and poor survival of HCC patients. Our in vitro
      experiments found that overexpression of miR-23c inhibited cell proliferation and
      induced apoptosis of HCC cells. While miR-23c knockdown led to HCC cell growth
      arrest and apoptosis. Additionally, miR-23c overexpression repressed tumor growth
      of HCC in vivo. Mechanistically, erbb2 interacting protein (ERBB2IP) was
      identified as a direct target of miR-23c in HCC cells. miR-23c suppressed ERBB2IP
      expression in HCC cells and inversely correlated with ERBB2IP mRNA expression in
      HCC tissues. Notably, ERBB2IP silencing restrained HCC cell proliferation and
      induced apoptosis. ERBB2IP restoration reversed the inhibitory effects of miR-23c
      on HCC cell growth. In conclusion, our observations suggested that miR-23c
      inhibited cell proliferation and accelerated apoptosis by attenuating ERBB2IP.
      Targeting miR-23c might open a new avenue for HCC treatment.

PMID- 30103115
TI  - Caffeic acid protects against IL-1beta-induced inflammatory responses and
      cartilage degradation in articular chondrocytes.
AB  - Osteoarthritis (OA) is a common articular disease that features cartilage loss
      and destruction. It has been confirmed that inflammation plays major roles in the
      progression of osteoarthritis. Caffeic acid (CA), a key dietary nutrient commonly
      found in coffee, has shown its anti-inflammatory properties in various
      inflammation diseases. However, the effects of CA in osteoarthritis remain
      explored. Here we investigated the effects of CA on IL-1beta induced increased
      expression of inflammatory factors as well as the degradation of Collagen II and
      aggrecan in rat chondrocytes. CA prevented the cartilage damage induced by IL
      1beta in vivo organ culture of articular cartilage. Besides, the IL-1beta induced
      increased production of inflammation factors such as iNOS and COX2 could be
      inhibited by CA. Additionally, CA could also suppress IL-1beta induced expression
      of cartilage matrix catabolic enzymes such as ADAMTS5 and MMPs. Moreover, CA
      could prevent IL-1beta induced degradation of Collagen II and aggrecan in
      chondrocytes. Furthermore, CA inhibited NF-kappaB activity and the activation of
      JNK pathway. This study reveals that CA inhibits IL-1beta induced inflammation
      responses through suppression of NF-kappaB and MAPK related JNK signaling
      pathways. These results demonstrate that CA may provide new avenues for
      osteoarthritis treatment in future.

PMID- 30103116
TI  - Omentin-1 protects renal function of mice with type 2 diabetic nephropathy via
      regulating miR-27a-Nrf2/Keap1 axis.
AB  - Omentin-1, a novel identified adipokine, always significantly decreases in
      patients with metabolic syndrome. However, the functional roles of omentin-1 in
      diabetic nephropathy (DN) remains largely unknown. In the present study, we found
      that omentin-1 treatment could improve renal function of type 2 diabetic db/db
      mice. ELISA assay and immunohistochemistry staining showed that omentin-1 reduced
      the productions of proinflammatory cytokines (IFN-gamma, TNF-alpha, MCP-1 and IL
      8), and improved oxidative stress level (CAT, MDA and SOD) in the kidney tissue,
      indicating omentin-1 could relieved the inflammatory response and suppressed
      oxidative stress. Mechanistic analysis demonstrated that omentin-1 down-regulated
      miR-27a expression, and subsequently inhibited oxidative stress and inflammation.
      Luciferase reporter assay and western blot further revealed that miR-27a directly
      targeted the 3' untranslated region (UTR) of nuclear factor erythroid 2-like 2
      (Nrf2) and reduced its expression in type 2 DN. Taken together, these findings
      provide a new function of omentin-1 in renal protection and also delineate
      multiple potential targets for therapeutic intervention for type 2 DN.

PMID- 30103117
TI  - Understanding the prospective of nano-formulations towards the treatment of
      psoriasis.
AB  - Psoriasis is a consistently recurring, inflammatory, autoimmune disorder of the
      skin, affecting about 2-5% of the world population. Abundant therapeutic agents
      are accessible for the treatment of psoriasis. Nevertheless, none of them are
      entirely secure and effective to treat the disease without compromising patient
      compliance. Furthermore, already existing drugs are supposed to restrain the
      ailment and alleviate the sign and symptoms with no complete cure. However, they
      focus on restraining the disease and alleviating the symptoms without providing
      an absolute cure. Therefore there remains a vital challenge, to explore a new
      drug moiety or delivery system which could safely and effectively manage
      psoriasis without compromising patient compliance. Furthermore, conventional
      formulations offer reduced benefit/risk ratio of anti-psoriatic drugs, which
      limits the use of existing conventional formulations. Novel formulations based on
      nanocarriers are a promising prospect to overcome the limitation of conventional
      formulations by offering a reduction in dose, dosing frequency, dose-dependent,
      side effects with enhanced efficacy. Presently nano-formulations have gained
      widespread application for effective and safe treatment of psoriasis. The present
      review primarily focuses on conventional therapeutic strategy and recent advances
      in lipid-based, polymer-based and metallic nano-formulations of a variety of anti
      psoriatic drugs. The practicability of various nanocarrier systems including
      liposomes, nanostructured lipid carriers, ethosomes, solid lipid nanoparticles,
      nanocapsules, micelles, dendrimers, gold nanoparticles and silver nanoparticles
      have been discussed in detail. The review also traces related patents to
      exemplify the role of various nanoparticles in psoriasis treatment. In a
      nutshell, nano-formulations remain established as a promising modality for
      treating psoriasis treatment as they propose better penetration, targeted
      delivery, enhanced safety, and efficacy.

PMID- 30103118
TI  - Quantitation of residual host cell DNA in protaminesulfate drug product by qPCR.
AB  - Protamine sulfate (PS) is an FDA approved drug used to reverse heparin-induced
      anticoagulation in patients. Protamine sulfate is a mixture of primarily four ~4
      kDa arginine-rich cationic polypeptide chains derived from chum (Oncorhynchus
      keta) salmon sperm. Because the presence of residual host cell salmon DNA
      (resDNA) in PS drug product can pose safety concerns, processing steps during PS
      manufacturing are designed to target the reduction of these impurities. However,
      given protamine's positively charged structure, isolating and measuring
      negatively charged residual DNA is challenging. Here, the development of a
      sensitive detection method using real-time quantitative polymerase chain reaction
      (qPCR) assay for a multicopy gene (5S ribosomal DNA) using custom-designed
      primers and TaqMan probes is described. The PS qPCR standard curve was accurate
      over a linear range of 0.0025-156.25 pg/MUL using protease-digested research
      grade salmon sperm DNA (neat) as the reference standard. DNA present in PS drug
      products was extracted using an optimized two-hour procedure achieving ~85%
      recovery values from 1 to 125 pg reference DNA spiked into PS (1 mg) samples. The
      procedure lower limit of quantitation (LLOQ) of 5 pg of DNA per mg of PS or 250
      pg of DNA per 50 mg dose of PS was determined from DNA spike recovery curves
      using the acceptance criteria of 70-130% recovery with % CV <= 25%. Seven
      pharmaceutical-grade lots of PS were evaluated and the detectable amount of
      resDNA was below the LLOQ. This qPCR method demonstrated sensitivity 40-fold
      above the current guidelines for resDNA (10 ng DNA per dose). Overall, the
      approach offers a promising tool for monitoring resDNA in PS and potentially
      other challenging complex drug products with cationic character.

PMID- 30103119
TI  - The influence of residue in the position of 116 on the inhibitory potency of
      TH588 for MTH1.
AB  - As one of the first-in-class inhibitor, TH588 was found to be efficient in the
      suppression of MutT homolog1 (MTH1). A recent work shows that the inhibitory
      potency of TH588 against human MTH1 (hsMTH1) is approximately 20-fold over that
      of mouse MTH1 (mmMTH1) and identifies residue in position 116 in MTH1 has an
      important contribution to TH588 affinity. But the effect of residue Leu or Met in
      position 116 on the binding affinity remains unclear. In this study, molecular
      dynamics (MD) simulations and free energy calculations were used to elucidate the
      mechanism about the effect of residue 116 to the different inhibitory potency of
      TH588 against MTH1. The binding free energy of TH588 in M116 complexes predicated
      by the Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) is much lower
      than that in L116 complexes, which is consistent with the experiment results. The
      analysis of the individual energy terms suggests that the non-polar interactions
      are important for distinguishing the binding of TH588. The MD results show that
      the Leu116 disrupts the interactions between Asn33 and TH588, thus induces the
      conformational changes of Asn33 as well as TH588. The altered interactions
      between TH588 and mmMTH1 change the flexibility of TH588, which could induce the
      remarkable conformational fluctuation of mmMTH1. The conformations of the two
      loops covering the binding pocket have obvious influence on the opening or
      closure of the active site. The more open binding site may explain the lower
      inhibitor potency of TH588 against mmMTH1 than hsMTH1. Our results provide
      mechanistic insight into the effect of different residue Leu or Met in position
      116 on the binding affinity of TH588 for MTH1, which is expected to contribute to
      the further rational design of more potent inhibitors.

PMID- 30103120
TI  - Polychlorinated biphenyls (PCBs) exposure and cardiovascular, endocrine and
      metabolic diseases: A population-based cohort study in a North Italian highly
      polluted area.
AB  - BACKGROUND AND AIMS: Exposure to polychlorinated biphenyls (PCBs) has been linked
      to the onset of cardiovascular, endocrine, and metabolic diseases, but no
      conclusive evidence has been provided so far. A chemical factory produced PCBs
      from 1938 to 1984 in Brescia (North Italy) resulting in environmental
      contamination and human exposure. We aimed to evaluate the association between
      PCB serum levels and subsequent incidence of chronic diseases through a
      prospective cohort study design. METHODS: Based on surveys conducted in Brescia
      province between 2001 and 2013, a cohort of 1331 subjects with at least one
      measure of PCB serum levels during the period was selected and followed
      longitudinally. Serum concentration of total PCBs was computed summing up the
      levels of 24 PCB congeners determined by gas chromatography. The data on
      incidence of hypertension, cardiovascular diseases, and endocrine and metabolic
      chronic diseases were retrieved from the Brescia Health Protection Agency
      database. Poisson regression models adjusted for age, level of education, BMI,
      cholesterol level, tobacco smoking and alcohol drinking were employed to
      calculate rate ratios (RRs). RESULTS: 1331 subjects were enrolled (45.7% males,
      mean age 50.6 years) contributing to 10,006 person-years of follow-up. A dose
      response relationship was observed between PCB serum levels and the onset of
      hypertension (RR for 2nd and 3rd tertiles of serum PCB distribution: 2.07, 95% CI
      1.18-3.63, and 2.41, 1.30-4.47, respectively). A possible, though not
      statistically significant, increase of the risk of cardiovascular disease was
      also found (RR for 2nd and 3rd tertiles of serum PCB distribution: 1.61, 0.72
      3.64, and 1.96, 0.86-4.48, respectively). The results based on lipid-standardized
      PCBs were slightly attenuated. No association was found between PCB serum levels
      and occurrence of diabetes and endocrine disorders. Stratified analysis by body
      mass index showed an increased risk of hypertension in subjects at 2nd and 3rd
      tertile of serum PCB distribution in overweight/obese subjects only. CONCLUSIONS:
      These results suggest that PCBs might play a role in the development of
      hypertension and possibly cardiovascular disease, though alternative explanations
      are to be considered too.

PMID- 30103121
TI  - Associations of Salmonella hospitalizations with ambient temperature, humidity
      and rainfall in Hong Kong.
AB  - BACKGROUND: Little is known about the relationship between Salmonella infection
      and meteorological parameters other than air temperature. This study aimed to
      explore associations of Salmonella hospitalizations with temperature, relative
      humidity (RH) and rainfall. METHODS: With negative binomial distribution assumed,
      time-series regression model adjusting for season and time trend were constructed
      employing distributed lag non-linear models and generalized additive models.
      Meteorological variables including mean temperature, RH, and daily total rainfall
      as well as indicator variables including day of the week and public holiday were
      incorporated in the models. RESULTS: Higher temperature was strongly associated
      with more hospitalizations over the entire range of temperatures observed. There
      was a net 6.13 (95%Confidence Interval (CI) 3.52-10.67) relative risk of
      hospitalization at a temperature of 30.5  degrees C, relative to 13  degrees C,
      lag 0-16 days. Positive associations were found for RH above 60% and rainfall
      between 0 and 0.14 mm. Extreme high humidity (96%) and trace rainfall (0.02 mm)
      were associated with 2.06 (95%CI 1.35-3.14), lag 0-17 day, and 1.30 (95%CI 1.01
      1.67), lag 0-26 days, relative risks of hospitalizations, relative to 60% and no
      rain, respectively. CONCLUSIONS: High temperatures, high RH and light rainfall
      are positively associated with Salmonella hospitalizations. The very strong
      association with temperatures implies that hotter days will lead to increases in
      Salmonella morbidity in the absence of other changes, and the public health
      implications of this could be exacerbated by global climate change.

PMID- 30103122
TI  - Impact of exposure to phenols during early pregnancy on birth weight in two
      Canadian cohort studies subject to measurement errors.
AB  - BACKGROUND: It is of interest to know whether early pregnancy exposure to phenols
      such as bisphenol-A (BPA) or triclosan (TCS) negatively impacts birth weight
      outcomes. Exposure to these chemicals is widespread in the Canadian population
      but obtaining accurate measurements of average exposure is difficult because
      these chemicals are rapidly excreted from the body, causing body levels to
      fluctuate both within and between days, as observed in a recent Canadian study
      (P4). This measurement error can attenuate the estimated effects of exposures.
      METHODS: Data from two Canadian cohort studies, the Plastics and Personal-care
      Products use in Pregnancy (P4) Study and the Maternal-Infant Research on
      Environmental Chemicals (MIREC) Study, such that all participants with complete
      BPA or TCS exposure and outcome data were used (MIREC n = 1822, P4 n = 68). We
      used regression calibration to correct for the attenuating effects of exposure
      measurement error when modeling the effect of first trimester BPA or TCS exposure
      on four birth weight outcomes: birth weight (BW), low birth weight (LBW), small
      for gestational age (SGA) and large for gestational age (LGA). Specific gravity,
      time of day, and time since last urine void were also controlled in the analysis.
      RESULTS: TCS exposure has a marginally significant association with SGA only with
      odds ratio 0.87 and 95% confidence interval (0.74, 1.00). It also has a
      marginally significant association with LGA in male offspring with odds ratio
      1.11 and 95% confidence interval (1.00, 1.25). The effects of BPA on the four
      birth outcomes were insignificant. CONCLUSIONS: Increased TCS exposure during
      pregnancy is marginally associated with decreased odds of having SGA offspring.
      It is possibly associated with decreased BW in males and decreased odds of LBW,
      though these associations were not present in measurement error corrected models.
      TCS is possibly associated with increased odds in male offspring of being LGA,
      though this relationship was not present in models not corrected for measurement
      error. The study finds no significant effects of BPA on birth weight outcomes,
      which may be due to more severe measurement error in a single observation of BPA.

PMID- 30103123
TI  - Children are particularly vulnerable to environmental tobacco smoke exposure:
      Evidence from biomarkers of tobacco-specific nitrosamines, and oxidative stress.
AB  - BACKGROUND: Worldwide, smoking is a major public health problem, with exposure to
      environmental tobacco smoke (ETS) affecting both smokers, and passive smokers,
      including children. Despite ETS also describing secondhand, and thirdhand smoke
      (SHS, and THS respectively), the health effects of exposure to passive smoking
      via these sources are not fully understood, particularly in children. Although
      cotinine, the primary proximate metabolite of nicotine, has been widely used as a
      biomarker of ETS exposure, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL),
      the metabolite of the tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), provides a uniquely important contribution, both as a
      biomarker of exposure, and as a specific risk indicator for pulmonary
      carcinogenesis. METHODS: We used LC-MS/MS to study NNK metabolites, cotinine, and
      8-oxo-7,8-dihydro-2'-deoxyguanosine (a biomarker of oxidative stress), in the
      urine of 110 non-smoking adults (age range: 23-62) and 101 children (age range: 9
      11), exposed to ETS. RESULTS: In our study of passive smoking adults, and
      children exposed to ETS, we showed that although the children had a similar
      urinary level of cotinine compared to the adults, the children had approximately
      two times higher levels of urinary total NNAL (P = 0.002), and free NNAL (P =
      0.01), than adults. The children also had three times lower ability to detoxify
      NNK than adults (P < 0.001). Furthermore, the children showed 1.5 times higher
      ratio of total NNAL/cotinine than adults (P = 0.01), implying that THS is another
      important source of ETS in this population. Furthermore, ETS exposure in children
      appeared to lead to an increase in levels of oxidative stress. CONCLUSIONS: Taken
      together, our results demonstrate that, in children, THS may play an important
      role in the ETS exposure, and that children are at particular risk of ETS-induced
      health effects.

PMID- 30103125
TI  - A review of factors surrounding the air pollution exposure to in-pram babies and
      mitigation strategies.
AB  - Air pollution exposure to in-pram babies poses a serious threat to their early
      childhood development, necessitating a need for effective mitigation measures. We
      reviewed the scientific and grey literature on in-pram babies and their personal
      exposure to traffic generated air pollutants such as particulate matter <=10 MUm
      (PM10), <=2.5 MUm (PM2.5), <=0.10 MUm (ultrafine particles) in size, black carbon
      and nitrogen oxides and potential mitigation pathways. In-pram babies can be
      exposed up to ~60% higher average concentrations depending on the pollutant types
      compared with adults. The air within the first few meters above the road level is
      usually most polluted. Therefore, we classified various pram types based on
      criteria such as height, width and the seating capacity (single versus twin) and
      assessed the breathing heights of sitting babies in various pram types available
      in the market. This classification revealed the pram widths between 0.56 and 0.82
      m and top handle heights up to ~1.25 m as opposed to breathing height between
      0.55 and 0.85 m, suggesting that the concentration within the first meter above
      the road level is critical for exposure to in-pram babies. The assessment of flow
      features around the prams suggests that meteorological conditions (e.g., wind
      speed and direction) and traffic-produced turbulence affect the pollution
      dispersion around them. A survey of the physicochemical properties of particles
      from roadside environment demonstrated the dominance of toxic metals that have
      been shown to damage their frontal lobe as well as cognition and brain
      development when inhaled by in-pram babies. We then assessed a wide range of
      active and passive exposure mitigation strategies, including a passive control at
      the receptor such as the enhanced filtration around the breathing zone and
      protection of prams via covers. Technological solutions such as creating a clean
      air zone around the breathing area can provide instant solutions. However, a
      holistic approach involving a mix of innovative technological solutions,
      community empowerment and exposure-centric policies are needed to help limit
      personal exposure of in-pram babies.

PMID- 30103124
TI  - Review of global sanitation development.
AB  - The implementation of the United Nations (UN) Millennium Development Goals (MDGs)
      and Sustainable Development Goals (SDGs) has resulted in an increased focus on
      developing innovative, sustainable sanitation techniques to address the demand
      for adequate and equitable sanitation in low-income areas. We examined the
      background, current situation, challenges, and perspectives of global sanitation.
      We used bibliometric analysis and word cluster analysis to evaluate sanitation
      research from 1992 to 2016 based on the Science Citation Index EXPANDED (SCI
      EXPANDED) and Social Sciences Citation Index (SSCI) databases. Our results show
      that sanitation is a comprehensive field connected with multiple categories, and
      the increasing number of publications reflects a strong interest in this research
      area. Most of the research took place in developed countries, especially the USA,
      although sanitation problems are more serious in developing countries.
      Innovations in sanitation techniques may keep susceptible populations from
      contracting diseases caused by various kinds of contaminants and microorganisms.
      Hence, the hygienization of human excreta, resource recovery, and removal of
      micro-pollutants from excreta can serve as effective sustainable solutions.
      Commercialized technologies, like composting, anaerobic digestion, and storage,
      are reliable but still face challenges in addressing the links between the
      political, social, institutional, cultural, and educational aspects of
      sanitation. Innovative technologies, such as Microbial Fuel Cells (MFCs),
      Microbial Electrolysis Cells (MECs), and struvite precipitation, are at the TRL
      (Technology readiness levels) 8 level, meaning that they qualify as "actual
      systems completed and qualified through test and demonstration." Solutions that
      take into consideration economic feasibility and all the different aspects of
      sanitation are required. There is an urgent demand for holistic solutions
      considering government support, social acceptability, as well as technological
      reliability that can be effectively adapted to local conditions.

PMID- 30103126
TI  - A review on health cost accounting of air pollution in China.
AB  - Over the last three decades, rapid industrialization in China has generated an
      unprecedentedly high level of air pollution and associated health problems. Given
      that China accounts for one-fifth of the world population and suffers from severe
      air pollution, a comprehensive review of the indicators accounting for the health
      costs in relation to air pollution will benefit evidence-based and health-related
      environmental policy-making. This paper reviews the conventional static and the
      new dynamic approach adopted for air pollution-related health cost accounting in
      China and analyzes the difference between the two in estimating GDP loss. The
      advantages of adopting the dynamic approach for health cost accounting in China,
      with conditions guaranteeing its optimal performance are highlighted. Guidelines
      on how one can identify an appropriate approach for health cost accounting in
      China are put forward. Further, we outline and compare the globally-applicable
      and China-specific indicators adopted by different accounting methodologies, with
      their pros and cons being discussed. A comprehensive account of the available
      databases and methodologies for health cost accounting in China are outlined.
      Future directions to guide health cost accounting in China are provided. Our work
      provides valuable insights into future health cost accounting research in China.
      Our study has strengthen the view that the dynamic approach is comparatively more
      preferred than the static approach for health cost accounting in China, if more
      data is available to train the dynamic models and improve the robustness of the
      parameters employed. In addition, future dynamic model should address the socio
      economic impacts, including benefits or losses of air pollution polices, to
      provide a more robust policy picture. Our work has laid the key principles and
      guidelines for selecting proper econometric approaches and parameters. We have
      also identified a proper estimation method for the Value of Life in China, and
      proposed the integration of engineering approaches, such as the use of deep
      learning and big data analysis for health cost accounting at the fine-grained
      level (city-district or sub-regional level). Our work has also identified the gap
      for more accurate health cost accounting at the fine-grained level in China,
      which will subsequently affect the quality of health-related air pollution policy
      decision-making at such levels, and the health-related quality of life of the
      citizens in China.

PMID- 30103127
TI  - In vitro inhalation bioaccessibility for particle-bound hydrophobic organic
      chemicals: Method development, effects of particle size and hydrophobicity, and
      risk assessment.
AB  - Bioaccessibility of particle-bound hydrophobic organic contaminants and related
      particle size effects are significant for assessing the potential human health
      risk via inhalation exposure, but have not been clearly evaluated. To fill this
      knowledge gap, the present study developed an in vitro method to estimate the
      inhalation bioaccessibility of particulate polycyclic aromatic hydrocarbons
      (PAHs) using simulated human lung fluids, i.e., a modified Gamble's solution
      (MGS) and artificial lysosomal fluid (ALF) with Tenax as the absorption media.
      Assay parameters, namely incubation time (10 d) and influence of filter use, were
      optimized for establishing the in vitro method. The results showed that the
      bioaccessibility of PAHs increased with increasing particle size, but other
      factors, such as total organic carbon and chemical hydrophobicity, also played a
      large role in the fate of these compounds. The results from this portion of the
      present study were then used to evaluate human health risk, which showed that the
      risk of these particle-bound PAHs by incorporating size-dependent PAHs
      bioaccessibility and deposition efficiency in the human respiratory tract into
      inhalation exposure risk calculations was reduced by >90% when compared to using
      total concentration. This suggested that the inhalation bioaccessibility and
      deposition efficiency of hydrophobic organic chemicals should be included in
      human health risk assessment.

PMID- 30103128
TI  - Reutilization of iron sludge as heterogeneous Fenton catalyst for the degradation
      of rhodamine B: Role of sulfur and mesoporous structure.
AB  - Fenton process has gained considerable interest for its application in water
      treatment. However, the removal of iron sludge which generated during the process
      makes this method complex and uneconomical. In this study, we report a novel way
      of modifying iron sludge and use it as heterogeneous Fenton catalyst for the
      degradation of dye wastewater. It was found that after calcination at 600 
      degrees C, the iron sludge (Fe-600) exhibited much enhanced catalytic performance
      (99%) toward rhodamine B (RhB) in comparison with iron sludge without calcination
      (10%) in the presence of H2O2. The mesoporous structure of Fe-600 could
      facilitate its adsorption and immobilization of RhB, and the self-doped lattice
      sulfide played an important role during the Fenton degradation process. Moreover,
      the Fe-600 exhibited excellent heterogeneous Fenton degradation efficiency of
      acid red G and methylene blue as well. Our results may shed new light on the
      scalable preparation of novel heterogeneous Fenton catalysts and make
      contribution to the application of homogeneous Fenton degradation of wastewater.

PMID- 30103129
TI  - Two-step hydrothermal synthesis of peanut-shaped molybdenum diselenide/bismuth
      vanadate (MoSe2/BiVO4) with enhanced visible-light photocatalytic activity for
      the degradation of glyphosate.
AB  - The novel peanut-like shaped MoSe2/BiVO4 composites were fabricated via a facile
      two-step hydrothermal method and their photocatalytic activity was evaluated by
      the degradation of glyphosate under the visible light irradiation. The efficient
      transfer of photogenerated carriers and the charge separation were confirmed by
      photoluminescence spectra (PL), electrochemical impedance spectroscopy (EIS) and
      photocurrent. The coupling of MoSe2 and BiVO4 remarkably enhanced the
      photocatalytic activity. The 0.15MoSe2/BiVO4 composite showed the highest
      photocatalytic performance for the degradation of glyphosate among all the as
      prepared photocatalysts and presented the high stability and good reusability in
      the photocatalytic reactions.

PMID- 30103130
TI  - Removal of Cu2+, Cd2+ and Pb2+ from aqueous solutions by magnetic alginate
      microsphere based on Fe3O4/MgAl-layered double hydroxide.
AB  - In this work, the magnetic alginate microsphere of Fe3O4/MgAl-LDH (Fe3O4/LDH-AM)
      was prepared by immobilizing the Fe3O4/LDH with calcium alginate (CA) and was
      used to remove Cd2+, Pb2+, and Cu2+ from aqueous solutions. The obtained
      Fe3O4/LDH-AM was characterized by X-ray diffraction, Fourier-transform infrared
      spectroscopy, scanning electron microscopy, energy dispersive spectroscopy, X-ray
      photoelectron spectroscopy, and Brunauer-Emmett-Teller surface area
      determination. The results indicated that the surface groups of the alginate and
      LDH were retained and so was the crystal structure in the alginate microsphere.
      The adsorption performance of the Fe3O4/LDH-AM for Cd2+, Pb2+, and Cu2+ in
      aqueous solutions was evaluated by batch and column adsorption experiments. The
      effects of adsorption conditions, kinetics, isotherms, mechanisms, and potential
      applications were investigated. The adsorption kinetic data conformed to the
      pseudo-second-order kinetic equation, and the isotherm data fit well with the
      Freundlich and Langmuir isotherm models. The adsorption mechanism of Cd2+, Pb2+,
      and Cu2+ by the Fe3O4/LDH-AM entailed complexation and precipitation. The
      experimental breakthrough curves were correlated with the Thomas model. Moreover,
      the Fe3O4/LDH-AM displayed superior regeneration and reusability. These results
      suggest that the Fe3O4/LDH-AM is an efficient adsorbent for the removal of heavy
      metals and can be effectively employed in practical applications.

PMID- 30103131
TI  - Investigation on the electrocatalytic activity and stability of three-dimensional
      and two-dimensional palladium nanostructures for ethanol and formic acid
      oxidation.
AB  - Three dimensional (3-D) self-supported noble metal nanostructures are attractive
      for their unique properties of high porosity, low density, excellent charge, and
      mass transfer which increases catalytic activity. Herein, a facile route of
      preparing two-dimensional (2-D) palladium nanosheets and three-dimensional
      palladium nanostructure is introduced. By raising the temperature of the reaction
      mixture, it is possible for Pd nanosheets to change from 2-D into the 3-D
      structure. Morphology and chemical composition of the nanostructures are
      characterized by Transition Electron microscopy (TEM), Scanning Electron
      Microscopy (SEM) and Energy Dispersive X-Ray Spectroscopy (EDX). We reveal that
      the as-prepared 3-D Pd nanostructure shows a higher electrocatalytic activity and
      stability towards ethanol oxidation reaction (EOR) than 2-D Pd nanosheets, due to
      its porous nanostructures that renders a high surface area.

PMID- 30103132
TI  - Cobalt sulfide thin films for electrocatalytic oxygen evolution reaction and
      supercapacitor applications.
AB  - Nanocrystalline cobalt sulfide thin film electrodes have been deposited on
      stainless steel substrate using binder-free chemical bath deposition (CBD) method
      and electrochemical study is performed in 1 M KOH electrolyte. Linear sweep
      voltammetry (LSV) curve shows that cobalt sulfide thin film electrode requires
      300 mV overpotential (n) to reach the current density of 10 mA cm-2. Also, it
      exhibits Tafel slope of 57 mV decade-1 with stable catalytic activity over 14 h.
      Along with good electrocatalytic oxygen evolution performance, in supercapacitive
      study it shows specific capacitance of 252.39 F g-1 at a scan rate of 5 mV s-1.
      The stability test indicates that cobalt sulfide electrode is stable for 1000
      cyclic voltammetry (CV) cycles.

PMID- 30103133
TI  - Hydrous CeO2-Fe3O4 decorated polyaniline fibers nanocomposite for effective
      defluoridation of drinking water.
AB  - Hydrous CeO2-Fe3O4 (HCeFe) decorated polyaniline nanofibers (HCeFe NFs) were
      obtained through a simple co-precipitation deposition approach on pre-synthesized
      polyaniline nano-fibers (PANI NFs), and evaluated as adsorbents for fluoride
      removal from synthetic and real water samples. Field emission scanning electron
      microscopy/energy dispersive X-ray spectroscopy (FE-SEM/EDS), high resolution
      transmission electron microscopy (HR-TEM), Braunauer-Emmett-Teller (BET), X-ray
      diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR),
      thermogravimetric-differential thermal analysis (TGA-DTA), X-ray photoelectron
      spectroscopy (XPS) and dynamic mechanical analysis (DMA) techniques were used to
      characterize the hybrid nanomaterials. The optimised HCeFe NFs adsorbent with
      specific surface area 66 m2/g, exhibited excellent adsorption efficiency towards
      fluoride ions (F-) via both electrostatic interactions and ion exchange
      mechanisms. F- adsorption followed the pseudo-second-order rate model and best
      fitted the Langmuir isotherm, with the maximum capacities within 93.46-117.64
      mg/g over a broad pH range 3-10, respectively. The determined thermodynamic
      parameters, including enthalpy (DeltaH degrees  - 15.1 kJ/mol) and Gibbs free
      energies change (DeltaG degrees  < 0) indicated to the exothermic and a
      spontaneous nature of the sorption process. The regeneration of HCeFe NFs showed
      a considerable adsorption-desorption efficiency over three consecutive cycles.
      Ultimately, the adsorbent was tested on spiked F- containing groundwater and the
      obtained results demonstrated its potential utility for defluoridation of natural
      water.

PMID- 30103134
TI  - Novel fabrication of polymer/carbon nanotube composite coated Janus paper for
      humidity stress sensor.
AB  - In this work, we constructed a sensing system on Janus paper with hydrophilic
      side and hydrophobic side via depositing polymer precursor onto one side of
      qualitative filter paper. Water in humid environment (including liquid water,
      condensed moisture airflow and gaseous humid atmosphere) will be captured and
      gathered in the hydrophilic region of Janus paper due to the asymmetric
      hydrophobicity and hygroscopicity, which can induce the novel directional
      deformation. Additionally, MWCNTs (multiwalled carbon nanotubes) were loaded onto
      hydrophobic region beforehand to construct conductive network. The resistance of
      the conductive network changes synergistically as the Janus paper deforms in
      humid environment. Thus, the novel Janus paper realized the induction of
      environment humid factors, and conversion from the deformation signals to the
      desirable electric signals. The Janus paper also shows excellent stability in
      cycle use.

PMID- 30103135
TI  - Flexible hybrid yarn-shaped supercapacitors based on porous nickel cobalt sulfide
      nanosheet array layers on gold metalized cotton yarns.
AB  - A high-performance yarn-shaped supercapacitor electrode material with light
      weight, small volume, flexibility and low cost, is highly desirable for the
      development of flexible energy storage devices. Herein, a cotton/Au/nickel cobalt
      sulfide hybrid yarn electrode was designed and synthesized by electrodepositing
      nickel cobalt sulfide nanosheet arrays on the Au metalized cotton yarn. The
      metalized cotton yarn as a conductive substrate ensures rapid electron
      transportation. The porous layer which constructed by CoNi2S4 nanosheet arrays
      significantly enlarges the interface between the electrolyte ions and electrode
      materials, providing large electroactive surface area for the faradic redox
      reactions. The hierarchically porous structure of entire yarn electrode shortens
      the electrolyte diffusion path. A synergistic effect caused by the unique
      electrode structure greatly increases the electrochemical performance. This
      hybrid yarn electrode exhibits high specific capacitance of 1323 F/g at 1 A/g,
      good electrochemical stability and high flexibility with performance well
      maintained under the mechanical bending condition. An assembled two-ply
      structured all-solid-state symmetric supercapacitor device delivers an energy
      density of 40.9 Wh/kg at a power density of 1.43 kW/kg.

PMID- 30103136
TI  - Alternating current (AC) susceptibility as a particle-focused probe of coating
      and clustering behaviour in magnetic nanoparticle suspensions.
AB  - HYPOTHESIS: The functionality of magnetic nanoparticles (MNPs) relies heavily on
      their surface coating, which in turn affects the interactions between MNPs, and
      the formation of single-core particles or multi-core clusters. In this study we
      assessed the use of AC susceptibility (ACS) as a magnetic probe of the kinetics
      of coating and agglomeration of functionalised nanoparticles. We demonstrate the
      precision and sensitivity of ACS measurements to small changes in MNP coating
      using arginine-glycine-aspartic acid (RGD) tripeptide binding, and subsequently
      discuss how ACS can be used to optimise the preparation of polyethyleneimine
      (PEI) functionalised MNPs aimed at nanomagnetic transfection applications.
      EXPERIMENTS: We varied the PEI loading of suspensions of MNPs exhibiting a
      combination of Brownian and Neel relaxation, and used dialysis to study the
      movement of excess PEI during the coating process. Numerical ACS simulations were
      employed to determine particle cluster sizes and polydispersity and the results
      compared with conventional dynamic light scattering (DLS) size measurements.
      FINDINGS: ACS provided information on the MNP coating and agglomeration process
      that was not accessible through DLS due to the additional presence of non
      magnetic polymer particulates in the suspensions. We consequently derived a
      simple method to obtain dense, uniform PEI coatings affording high-stability
      suspensions without excessive quantities of unbound PEI.

PMID- 30103137
TI  - Does time since fire drive live aboveground biomass and stand structure in low
      fire activity boreal forests? Impacts on their management.
AB  - Boreal forests subject to low fire activity are complex ecosystems in terms of
      structure and dynamics. They have a high ecological value as they contain
      important proportions of old forests that play a crucial role in preserving
      biodiversity and ecological functions. They also sequester important amounts of
      carbon at the landscape level. However, the role of time since fire in
      controlling the different processes and attributes of those forests is still
      poorly understood. The Romaine River area experiences a fire regime characterized
      by very rare but large fires and has recently been opened to economic development
      for energy and timber production. In this study, we aimed to characterize this
      region in terms of live aboveground biomass, merchantable volume, stand structure
      and composition, and to establish relations between these attributes and the time
      since the last fire. Mean live aboveground biomass and merchantable volume showed
      values similar to those of commercial boreal coniferous forests. They were both
      found to increase up to around 150 years after a fire before declining. However,
      no significant relation was found between time since fire and stand structure and
      composition. Instead, they seemed to mostly depend on stand productivity and non
      fire disturbances. At the landscape level, this region contains large amounts of
      biomass and carbon stored resulting from the long fire cycles it experiences.
      Although in terms of merchantable volume these forests seemed profitable for the
      forest industry, a large proportion were old forests or presented structures of
      old forests. Therefore, if forest management was to be undertaken in this region,
      particular attention should be given to these old forests in order to protect
      biodiversity and ecological functions. Partial cutting with variable levels of
      retention would be an appropriate management strategy as it reproduces the
      structural complexity of old forests.

PMID- 30103138
TI  - Determination of levels of some metal contaminants in the freshwater environments
      of Osun State, Southwest Nigeria: A risk assessment approach to predict health
      threat.
AB  - This study evaluated levels of heavy metals and macro-elements in ten major
      rivers in Osun State, Southwest Nigeria. Triplicate water samples collected from
      selected rivers were analyzed for metal pollutants by atomic absorption
      spectrophotometry. Concentrations were obtained as follows: iron: 60-960 MUg L-1;
      manganese: ND - 3 MUg L-1; chromium 0-2100 MUg L-1; aluminium: 0-800 MUg L-1;
      copper: 0-1350 MUg L-1; zinc: 10-650 MUg L-1; calcium: 6400-232000 MUg L-1 and
      magnesium: 2000-71000 MUg L-1 but lead was not detected. While most of the
      parameters fell within the threshold values for drinking water, iron, chromium,
      aluminium and calcium exceeded at some locations. The pollution order of the
      rivers, especially with heavy metals had the order: R8 > R3 > R2 > R5 > R10 > R6
      > R4 > R1 > R7 > R9; which implies that R8 and R3 are the most polluted. The
      health risk assessment results revealed that hazard quotient and hazard index
      were below the acceptable limit of 1.0, suggesting no substantial non
      carcinogenic effect would arise from individual exposure to the elements.
      However, the carcinogenic risks were 3.18 * 10-6 and 4.43 * 10-6 for adults and
      children, respectively at R8, implying that 1 person in 314,206 adults and
      225,836 children drinking from the water may be at risk of having cancer
      correspondingly. Hence, there is need to moderate the levels of these pollutants
      in these waterbodies to safeguard public health.

PMID- 30103139
TI  - Changes in thyroid axis responses in two ring-billed gull sub-populations
      differentially exposed to halogenated flame retardants.
AB  - Developing bird embryos may be affected by a number of thyroid disrupting
      chemicals through maternal transfer. However, thyroid disruption in developing
      embryos of wild birds remains largely unstudied, especially with respect to
      exposure to ubiquitous environmental contaminant classes including halogenated
      flame retardants (HFRs). The objective of the present study was to investigate
      responses of the hypothalamic-pituitary-thyroid (HPT) axis of developing birds
      that are exposed to elevated concentrations of HFRs in their environment. Ring
      billed gulls (Larus delawarensis) were collected at the external pipping stage
      (i.e., just prior to hatching) from two sub-populations that are differentially
      exposed to HFRs in the St. Lawrence River (QC, Canada). Plasma levels of thyroid
      hormones (THs) and transcription levels of thyroid-related genes in three tissues
      (i.e., liver, thyroid gland and brain) were related to liver concentrations of
      HFRs in pipping gulls from these two colonies. Liver polybrominated diphenyl
      ether (PBDE) concentrations were negatively correlated with plasma total T4 and
      total T4/T3 in pipping ring-billed gulls. Moreover, plasma TH levels and hepatic
      PBDE concentrations were correlated with the transcription of genes involved in
      metabolism (deiodinases type 1, 2 and 3) and synthesis (sodium iodide symporter
      and thyroglobulin) in the thyroid gland, negative feedback loop (thyrotropin and
      corticotropin releasing hormones) in the brain and the pituitary and targeted
      action (TH receptors) in the three tissues of gulls. The present study suggested
      that the alteration of TH homeostasis in developing wild birds through changes in
      the transcription of several thyroid-related genes may be related to potential
      PBDE-mediated effects.

PMID- 30103140
TI  - Zinc supplementation can reduce accumulation of cadmium in aged metallothionein
      transgenic mice.
AB  - Epidemiologic studies suggest that exposure to Cd is related to a multitude of
      age-related diseases. There is evidence that Cd toxicity emerges from an
      interference with Zn metabolism as they compete for the same binding sites of
      ligands. The most responsive proteins to Cd exposure are the metal-binding
      proteins termed metallothioneins (MTs), which display a much greater affinity for
      Cd than for Zn. Most studies have considered the effect of Zn on the accumulation
      of exogenous Cd and tissue damage, whereas observational studies have addressed
      the association between Zn intake and Cd levels in body fluids. However, it has
      not been addressed whether supplemental Zn can lower Cd levels in organs of
      healthy aged animals without affecting Cu stores, a question more pertinent to
      human aging. We therefore aimed to investigate the effect of Zn supplementation
      on Cd levels in liver and kidney of aged MT transgenic mice (MT1-tg)
      overexpressing MT1 at levels more comparable to those observed in humans than non
      transgenic mice. We found a >30% reduction of kidney and liver Cd levels in Zn
      supplemented MT1-tg mice compared to non-supplemented controls, independently of
      the dose of Zn, without a significant reduction of Cu. Our data support the idea
      of a causal and inverse relationship between Zn intake and Cd content in organs
      of aged MT1-tg mice as suggested by observational studies in humans. Our work
      provides the rationale for interventional studies to address the effects of Zn
      supplementation on Cd burden in elderly people.

PMID- 30103141
TI  - Phthalates in soft glass (a soft transparent PVC plastic sheet used extensively
      in household and public place in developing countries in recent years):
      Implication for oral exposure to young children.
AB  - It has been several years that a soft transparent polyvinyl chloride (PVC)
      plastic sheet, commonly known as "soft glass", or "crystal plate" in China and
      other developing countries, has quietly and gradually found extensive
      applications. This material has widely replaced cloth and glass as table cover in
      household and office, and replaced cloth as door drape in public place in China.
      In this study, the concentration of plasticizer used in soft glass and the
      migration of the plasticizer from soft glass to olive oil and porcine skin during
      contact were determined. The oral exposure of young children to the plasticizer
      from soft glass was estimated for the first time. Two exposure routes, one via
      ingestion of contaminated food, the other via mouthing of contaminated hand, were
      considered. It is found that Di(2-ethylhexyl) phthalate (DEHP) is the major
      plasticizer used in soft glass, which could leach out of the material and migrate
      easily to the olive oil and porcine skin during contact. A rough estimation of
      oral exposure for young children to DEHP from soft glass was 126 MUg/person/d,
      which would be converted to 12.6 MUg/kg bw/d and 7.9 MUg/kg bw/d, for body weight
      of 10 kg and 16 kg, respectively. The estimated exposure dosages would not pose
      immediate health hazard to the children. The implications of these dosages were
      also discussed.

PMID- 30103142
TI  - A novel combined process for efficient removal of Se(VI) from sulfate-rich water:
      Sulfite/UV/Fe(III) coagulation.
AB  - The efficient removal of Se(VI) from sulfate-rich water is challenging as most
      reported processes last for hours to days. In this study, a combined
      sulfite/UV/Fe(III) coagulation process was proposed for efficient Se(VI) removal
      from sulfate-rich water within a short time (~1 h). In the presence of sulfate
      (1000 mg L-1), over 99% of Se(VI) (initially at 10 mg L-1) could be reduced by
      sulfite (5.0 mM) with a UV dose of 16 J cm-2 (within 20 min) into Se(IV) as the
      sole observed product. An alkaline pH (>9) was required for the reduction
      process, which was naturally obtained with the addition of sulfite. Scavenging
      experiments with N2O and NO3- both indicated that hydrated electrons (eaq-) were
      responsible for Se(VI) reduction by sulfite/UV. The presence of chloride,
      sulfate, phosphate, and carbonate (up to 10 mM) showed negligible influence on
      Se(VI) reduction, whereas nitrate and humic acid inhibited Se(VI) reduction to
      different extents depending on their concentrations. By Fe(III) coagulation,
      Se(IV) in the co-presence of sulfite and sulfate was efficiently removed at an OH
      /Fe molar ratio of 1.8-2.8. The removal of Se(IV) by Fe(III) coagulation
      responded insignificantly to chloride, nitrate, or sulfate (up to 10 mM), whereas
      it was adversely affected at high levels of carbonate (10 mM) and phosphate (1
      mM). The combined sulfite/UV/Fe(III) coagulation process was validated for the
      efficient removal of Se(VI) from synthetic sulfate-rich solution, simulated
      wastewater, and authentic smelting wastewater (in 1.1 h). The introduced sulfite
      underwent minor consumption during UV irradiation and was almost (~90%) removed
      after coagulation.

PMID- 30103143
TI  - Sample as solid support in MSPD: A new possibility for determination of
      pharmaceuticals, personal care and degradation products in sewage sludge.
AB  - A method based on matrix-solid phase dispersion (MSPD), focused on the principles
      of green analytical chemistry, aimed at the use of alternative solid supports and
      less toxic solvents, was developed for the simultaneous determination of 19
      pharmaceuticals, 4 personal care products (PPCPs) and 4 degradation products in
      sewage sludge samples. Higher recoveries were achieved when 2 g sample was
      macerated for 5 min in a glass mortar, transferred to a centrifuge tube, and 1
      min vortex agitation with 5 mL methanol. The performance of the method was
      evaluated through linearity, recovery, precision (intra-day), method detection
      and quantification limits (MDL and MQL) and matrix effect. The calibration curves
      prepared in methanol and in the matrix extract showed a correlation coefficient
      ranging from 0.98 to 0.99. MQL values ranged from 1.25 to 1250 ng g-1. Recoveries
      between 50 and 120% were reached with RSDs lower than 20% for most compounds. The
      method presented low and medium matrix effects for most analytes. This method was
      successfully applied to real samples and of the 27 compounds determined,
      amitriptyline, carbamazepine, diclofenac, haloperidol, ketoconazole, miconazole,
      albendazole, mebendazole, thiabendazole, triclosan and triclocarban were detected
      in concentrations between 2.5 and 5400 ng g-1.

PMID- 30103144
TI  - Determination of the formation rate of phosphatidylethanol by phospholipase D
      (PLD) in blood and test of two selective PLD inhibitors.
AB  - Phosphatidylethanol (PEth) is an alcohol biomarker formed from
      phosphatidylcholine (PC) by the enzyme phospholipase D (PLD) in the presence of
      ethanol. A drinking study revealed individual differences in maximum PEth levels
      after drinking to a targeted blood alcohol concentration (BAC) of 0.1%. This
      seemed to be due to different PLD activities in the tested persons. Furthermore,
      post-sampling formation of PEth occurred in blood samples, still containing
      alcohol. Therefore, a standardized in vitro test for measuring individual PEth
      formation rates was developed. Two PLD inhibitors were tested for their potency
      to inhibit post-sampling PEth formation. PEth-negative blood samples were
      collected from a volunteer. Ethanol was added in different concentrations (0.01
      0.3% BAC) directly after blood sampling. The specimens were incubated at 37 
      degrees C. Aliquots were taken at the start of the incubation, and every hour
      until 8 h after start of incubation, and one sample was taken on subsequent days
      over 1 week. PEth 16:0/18:1 and PEth 16:0/18:2 were determined by online SPE-LC
      MS/MS. Furthermore, this test system was applied to blood samples of 12
      volunteers. For the inhibition tests, fresh blood (spiked with 0.1% ethanol) was
      spiked with 30, 300, 3000, or 30,000 nM of either halopemide or 5-fluoro-2
      indolyl-deschlorohalopemide (FIPI), and incubated at 37  degrees C. PEth
      concentrations were determined hourly over 5 h on the first day and once on day 2
      and day 3. PEth formation was linear in the first 7 h of incubation and dependent
      on the alcohol concentration. The formation rates of PEth 16:0/18:1 were 0.002
      MUmol L-1 h-1 (0.01% BAC), 0.016 MUmol L-1 h-1 (0.1% BAC), 0.025 MUmol L-1 h-1
      (0.2% BAC), and 0.029 MUmol L-1 h-1 (0.3% BAC). For PEth 16:0/18:2, the formation
      rates were 0.002 MUmol L-1 h-1 (0.01% BAC), 0.019 MUmol L-1 h-1 (0.1% BAC), 0.025
      MUmol L-1 h-1 (0.2% BAC), and 0.030 MUmol L-1 h-1 (0.3% BAC). Maximum
      concentrations reached 431 ng/mL (PEth 16:0/18:1) and 496 ng/mL (PEth 16:0/18:2)
      at 0.3% BAC after 3 days. Maximum velocity (vmax) was not reached under these
      conditions. PEth formation in blood of the 12 volunteers ranged between 0.011 and
      0.025 MUmol L-1 h-1 for PEth 16:0/18:1 and between 0.014 and 0.021 MUmol L-1 h-1
      for PEth 16:0/18:2. PEth formation in human blood was inhibited by halopemide in
      a concentration-dependent manner. However, a complete inhibition was not achieved
      by the applied maximum concentration of 30,000 nM. FIPI showed a better
      inhibition of PEth formation. A complete inhibition could be achieved by a
      concentration of 30,000 nM for the first 24 h (for PEth 16:0/18:1) and for 48 h
      (for PEth 16:0/18:2). Formation of PEth was found to be dependent on the BAC. As
      a consequence, it is essential to inhibit PLD activity after blood collection to
      avoid post-sampling formation of PEth in blood samples with a positive BAC.
      Inhibition of PEth formation was more effective using FIPI, compared to
      halopemide.

PMID- 30103145
TI  - Non-specific peaks generated by animal DNA during human STR analysis: Peak
      characteristics and a novel analysis method for mixed human/animal samples.
AB  - Forensic human identification (HID) laboratories occasionally encounter non
      specific peaks generated by non-human DNA. Casework samples for human short
      tandem repeat (STR) profiling may be contaminated by animal DNA because of the
      specific environment or situation from which they were obtained. Validation
      studies for HID kits have reported that non-specific peaks generated from some
      animals are observed near the human amelogenin peak. In this study, we first
      revealed that DNA sequences associated with the non-specific peaks generated from
      animal DNA differ from one animal family to the other. However, non-specific
      peaks cannot be analyzed using the remainder of polymerase chain reaction (PCR)
      products left over from conventional HID kits when human and animal DNA are
      mixed. To overcome this issue, we have developed a novel analysis method of using
      non-specific peaks generated from animal DNA in human STR profiling to identify
      the source of contaminating animal DNA at the family level. The method applied
      here is termed as blocking PCR, which involves selective animal DNA re
      amplification by blocking nontarget human amelogenin DNA amplification using an
      oligonucleotide probe that specifically binds to human amelogenin using the
      remaining PCR product from the HID kit. Our data demonstrated that HID and family
      discrimination among animals that are often encountered in forensic contexts
      could be performed simultaneously. This study enabled recovery of more
      information from limited quantities of casework samples contaminated with animal
      DNA, which would be useful for forensic HID scientists.

PMID- 30103146
TI  - NIST interlaboratory studies involving DNA mixtures (MIX05 and MIX13): Variation
      observed and lessons learned.
AB  - Interlaboratory studies are a type of collaborative exercise in which many
      laboratories are presented with the same set of data to interpret, and the
      results they produce are examined to get a "big picture" view of the
      effectiveness and accuracy of analytical protocols used across participating
      laboratories. In 2005 and again in 2013, the Applied Genetics Group of the
      National Institute of Standards and Technology (NIST) conducted interlaboratory
      studies involving DNA mixture interpretation. In the 2005 NIST MIX05 study, 69
      laboratories interpreted data in the form of electropherograms of two-person DNA
      mixtures representing four different mock sexual assault cases with different
      contributor ratios. In the 2013 NIST MIX13 study,108 laboratories interpreted
      electropherogram data for five different case scenarios involving two, three, or
      four contributors, with some of the contributors potentially related. This paper
      describes the design of these studies, the variations observed among laboratory
      results, and lessons learned.

PMID- 30103147
TI  - Detection of latent DNA.
AB  - Touch DNA is one of the most common sample types submitted for DNA profiling.
      There is currently no process to visualise the presence of such DNA deposited
      when a person makes direct contact with items of forensic relevance. This report
      demonstrates the effective use of Diamond Dye to bind to DNA and allow
      visualisation of deposited cellular material using a mini-fluorescence
      microscope. Volunteers made contact with a range of items typical of those
      submitted as part of a forensic investigation. Contact was for less than 5 s and
      occurred either 15 min after hands were washed to remove any traces of DNA, and
      therefore under controlled conditions, or at an undefined time post handwashing
      to mimic real-world scenarios. Diamond Dye bound to cellular material on all the
      items used and in all cases it was clear where the volunteers had made this brief
      contact. It was also clear where no contact had been made. DNA profiling was
      performed on a sub-set of samples to confirm that the cellular material viewed
      under the microscope was human in origin and deposited by the person contacting
      the item; this was the result obtained in every sample tested. Diamond dye is
      relatively inexpensive, simple to apply, binds to the DNA in 3 s or less, has no
      mutagenic effects at the concentrations used, does not affect subsequent DNA
      profiling, and does not bind effectively to bacterial DNA. In combination with a
      mini-fluorescence microscope, this proof-of-concept study shows that otherwise
      invisible DNA deposited by touch can be visualised. The position and amount of
      cellular material deposited during even brief contact can be recorded allowing
      targeted sampling in any further DNA typing of forensically-significant items.

PMID- 30103148
TI  - Overexpression of RCc3 improves root system architecture and enhances salt
      tolerance in rice.
AB  - Root system architecture represents an underexplored target for improving global
      crop yields. In this study, we investigated the biological role of the rice root
      specific gene RCc3 in improving root growth and responses to abiotic stress by
      overexpressing RCc3 in rice plants. RCc3 was induced by osmotic and heat stress.
      RCc3 overexpression produced pleiotropic phenotypes of improved root system
      architecture, including increased growth of primary root, adventitious roots and
      lateral roots at the seedling stage. Further study indicated that auxin
      accumulation in the root was increased through auxin local biosynthesis and polar
      auxin transport in RCc3 overexpression lines. At maturity, the plant height and
      panicle traits were also significantly enhanced in overexpression plants. Under
      osmotic and heat stress conditions, the root and shoot growth were less severely
      inhibited in RCc3 overexpressing transgenic plants than that in wild-type plants,
      and the transcript levels of abiotic stress-related genes were significantly
      increased. Moreover, overexpression of RCc3 remarkably enhanced the tolerance to
      salt stress, with the elevated activities of antioxidant enzymes. Taken together,
      the data showed that RCc3 overexpression can improve rice root system, promote
      plant growth, and enhance plant tolerance to salt stress.

PMID- 30103149
TI  - Facile and eco-friendly synthesis of functionalized iron nanoparticles for
      cyanazine removal in water.
AB  - Second generation herbicide is applied for broad leaf weeds and yearly grasses in
      the growing fields of bananas, pineapple, sugarcane - polluting water sources.
      Cyanazine removal is described on functionalized iron nano particles (nano
      adsorbent). The nano-adsorbent was developed via eco-friendly method,
      functionalized with 1-butyl-3-methylimidazolidium bromide followed by SEM, XRD
      and FT-IR characterization. Remaining cyanazine in water was examined by C18-HPLC
      method. The batch experimentation limits were 30.0 MUg/L (concen.), 30.0 min.
      (time) 7.0 (pH), 2.5 g/L (dose) and 25.0  degrees C temperature. The
      experimentation data followed Freundlich, Temkin Dubinin-Radushkevich and
      Langmuir isotherms. The values of DeltaG degrees , DeltaH degrees  and DeltaS
      degrees  were -7.41, -6.47 and -6.27 kJ/mol at 20, 25 and 30  degrees C temps.; 
      8.27 kJ/mol and -7.93 * 10-3 kJ/mol K. These observations shown removal process
      fast and exothermic. The removal obeyed pseudo-first-order and liquid film
      diffusion mechanism. The removal method was quick, eco-friendly, and cheap owing
      to be appropriate under usual situations of water assets. The removal method can
      be applied for cyanazine removal in different waters.

PMID- 30103150
TI  - Shear and extensional rheological characterisation of mucin solutions.
AB  - The objective of this work is to obtain a concise image of mucin's assembly,
      structure and mechanics in saliva imitating buffer, in comparison to low ionic
      strength solutions. The systems show shear and extensional thinning, coupled with
      very high Trouton ratios, that is an extensional viscosity dominated mucin flow.
      Low-shear oscillation shows weak gels forming at low ionic strengths, while
      viscous systems form at high ionic strength saliva imitating buffer. Nanoparticle
      tracking results suggest that ionic environment affects the self-assembly of
      mucin. Extensional elasticities are within the size order of the shear ones;
      while extensional elastic moduli are smaller to the shear ones. Relaxation times
      and surface tensions are concentration-dependent, suggesting the build-up of
      aggregated structures with the addition of new material. The above conclude to
      the existence of finely-tuned, weak structure-spanning mucin networks in saliva
      imitating buffer, reminiscent to the ones proposed for the bulk self-assembly of
      mucus.

PMID- 30103151
TI  - Improving dispersive property, biocompatibility and targeting gene transfection
      of graphene oxide by covalent attachment of polyamidoamine dendrimer and
      glycyrrhetinic acid.
AB  - The surface functional groups of GO have significant effects on the performances
      of GO-based gene delivery vector. In this work, the polyamidoamine (PAMAM)
      dendrimer and glycyrrhetinic acid (GA) were tethered onto the GO surface by one
      step covalently cross-linking method. The micro-morphology, surface functional
      groups, and zeta potential of the obtained GO-PAMAM-GA hybrid were characterized
      and verified. The effects of GA amount in the hybrid on the dispersive property
      in cell culture medium, in vitro cytotoxicity to human hepatocarcinoma (SMMC
      7721) and human embryonic kidney (HEK-293) cells, and gene (plasmid DNA of
      enhanced green fluorescent protein) transfection capacity were investigated in
      detail. Under optimal conditions, the obtained hybrid shows small average size
      (about 160 nm) and has very good dispersive stability (in 30 days) in cellular
      culture medium. Compared with the GO-PAMAM without GA modification, the GO-PAMAM
      GA hybrid exhibits greatly enhanced biocompatibility to the two cell lines. The
      cellular viability of SMMC-7721 cells still retains about 98% even the
      concentration of the hybrid up to 200 MUg mL-1. The gene transfection capacity of
      the GO-PAMAM has been improved about 50% through the GA functionalization.
      Moreover, the GO-PAMAM-GA hybrid possesses targeting gene transfection to SMMC
      7721 cells.

PMID- 30103152
TI  - Differential impact of disfiguring facial features on overt and covert attention.
AB  - Observers can form negative impressions about faces that contain disfiguring
      features (e.g., scars). Previous research suggests that this might be due to the
      ability of disfiguring features to capture attention - as evidenced by
      contrasting observers' responses to faces with or without disfiguring features.
      This, however, confounds the effects of salience and perceptual interpretation,
      i.e. whether the feature is seen as integral to the face, or separate from it.
      Furthermore, it remains unclear to what extent disfiguring features influence
      covert as well as overt attention. We addressed these issues by studying
      attentional effects by photographs of unfamiliar faces containing a unilateral
      disfigurement (a skin discoloration) or a visually similar control feature that
      was partly occluding the face. Disfiguring and occluding features were first
      matched for salience (Experiment 1). Experiments 2 and 3 assessed the effect of
      these features on covert attention in two cueing tasks involving discrimination
      of a (validly or invalidly cued) target in the presence of, respectively, a
      peripheral or central distractor face. In both conditions, disfigured and
      occluded faces did not differ significantly in their impact on response-time
      costs following invalid cues. In Experiment 4 we compared overt attention to
      these faces by analysing patterns of eye fixations during an attractiveness
      rating task. Critically, faces with disfiguring features attracted more fixations
      on the eyes and incurred a higher number of recurrent fixations compared to faces
      with salience-matched occluding features. Together, these results suggest a
      differential impact of disfiguring facial features on overt and covert attention,
      which is mediated both by the visual salience of such features and by their
      perceptual interpretation.

PMID- 30103153
TI  - Qualitative findings from an Australian study of inter-partner violence content
      within undergraduate health curriculum.
AB  - : Health care professionals are frequently one of the first points of contact in
      episodes of intimate partner violence (IPV). This paper presents qualitative data
      from a larger research project on IPV-related content in undergraduate curriculum
      for Australian health care professionals. IPV is a serious public health issue
      with findings from this paper supporting the proposition that key health care
      workers such as nurses, midwives and paramedics are ill prepared to respond to
      the challenges it poses. OBJECTIVE: This study sought to better understand the
      barriers and facilitators to the inclusion of IPV-related content into
      undergraduate curricula for nurses, midwives and paramedics. DESIGN: A multiple
      phase, mixed method case study design was the overarching research framework.
      SETTING: This is the first national study on the topic in Australia. PARTICIPANTS
      AND METHODS: Guided conversations with 18 academics teaching into undergraduate
      nursing, midwifery and paramedicine courses across Australia. RESULTS AND
      CONCLUSIONS: There is a paucity of IPV-related content, with curriculum crowding
      being a major barrier to its inclusion. Additionally, the qualitative data
      suggests that IPV is not accepted by academics as being central to the role of a
      health care professional generally, and nursing more specifically. When
      contrasted to the emergent needs of those who experience IPV the findings from
      this study suggest that greater priority should be placed on increasing IPV
      related content and academic's capability to teach that content.

PMID- 30103154
TI  - Overexpression of miRNA 4451 is Associated With a Poor Survival of Patients With
      Hypopharyngeal Cancer After Surgery With Postoperative Radiotherapy.
AB  - Hypopharyngeal cancer (HC) is the most common subset of head and neck cancers.
      These tumors often have an aggressive clinical outcome characterized by local
      invasion and regional nodal metastasis. Upregulated miRNAs might be useful as
      biomarkers for prognosis and molecular targets for these tumors. We determined
      tumor expression of candidate miRNAs using microarray in 8 HC patients and
      validated in 372 HC patients. We also used paired tumorous and mucosal tissue to
      verify the miRNA expression. Log-rank test and Cox model were used to evaluate
      the survival; and Harrell's C-index was used to compare concordance of Cox
      models. Our results indicated 7 miRNAs aberrantly expressed in HC. Three of these
      candidate miRNAs (miRNA-4415, miRNA-200a, and miRNA-30b) were selected for
      further qRT-PCR validation and all of them were frequently found upregulated in
      HC tumors; with miR-4451 being the most differentially expressed. Moreover, high
      expression of miR-4451 was positively correlated with advanced tumor stage and
      increased mortality risk (HR: 1.6, 95% CI: 1.2-2.3; adjusted HR: 1.5, adjusted
      95% CI: 1.1-2.1). Finally, significantly higher expression of miR-4451 in tumors
      compared to in fresh adjacent normal tissues indicates an oncogenic role of miR
      4451 in this tumor. Upregulated miR-4451 in HC samples were frequently found and
      is significantly associated with advanced stage and poor survival of HC, which
      may indicate an association of this miRNA with the carcinogenesis process in this
      tumor site; and they could serve as a prognostic biomarker as well as help
      develop potential new targets for therapy.

PMID- 30103155
TI  - Noninvasive Anatomical and Functional Imaging of Orthotopic Glioblastoma
      Development and Therapy using Multispectral Optoacoustic Tomography.
AB  - PURPOSE: Here we demonstrate the potential of multispectral optoacoustic
      tomography (MSOT), a new non-invasive structural and functional imaging modality,
      to track the growth and changes in blood oxygen saturation (sO2) in orthotopic
      glioblastoma (GBMs) and the surrounding brain tissues upon administration of a
      vascular disruptive agent (VDA). METHODS: Nude mice injected with U87MG tumor
      cells were longitudinally monitored for the development of orthotopic GBMs up to
      15 days and observed for changes in sO2 upon administration of combretastatin A4
      phosphate (CA4P, 30 mg/kg), an FDA approved VDA for treating solid tumors. We
      employed a newly-developed non-negative constrained approach for combined MSOT
      image reconstruction and unmixing in order to quantitatively map sO2 in whole
      mouse brains. RESULTS: Upon longitudinal monitoring, tumors could be detected in
      mouse brains using single-wavelength data as early as 6 days post tumor cell
      inoculation. Fifteen days post-inoculation, tumors had higher sO2 of 63 +/- 11%
      (n = 5, P < .05) against 48 +/- 7% in the corresponding contralateral brain,
      indicating their hyperoxic status. In a different set of animals, 42 days post
      inoculation, tumors had lower sO2 of 42 +/- 5% against 49 +/- 4% (n = 3, P < .05)
      in the contralateral side, indicating their hypoxic status. Upon CA4P
      administration, sO2 in 15 days post-inoculation tumors dropped from 61 +/- 9% to
      36 +/- 1% (n = 4, P < .01) within one hour, then reverted to pre CA4P treatment
      values (63 +/- 6%) and remained constant until the last observation time point of
      6 hours. CONCLUSION: With the help of advanced post processing algorithms, MSOT
      was capable of monitoring the tumor growth and assessing hemodynamic changes upon
      administration of VDAs in orthotopic GBMs.

PMID- 30103157
TI  - Arch-shaped multiple-target sensing for rapid diagnosis and identification of
      emerging infectious pathogens.
AB  - Rapid identification of emerging infectious pathogens is crucial for preventing
      public health threats. Various pathogen detection techniques have been
      introduced; however, most techniques are time-consuming and lack multiple-target
      detection specificity. Although multiple-target detection techniques can
      distinguish emerging infectious pathogens from related pathogens, direct
      amplification methods have not been widely examined. Here, we present a novel
      arch-shaped multiple-target sensor capable of rapid pathogen identification using
      direct amplification in clinical samples. In this study, an arch-shaped
      amplification containing primer sequences was designed to rapidly amplify
      multiple targets. Further, the sensing platform allowed for sensitive and
      specific detection of human coronavirus, Middle East respiratory syndrome, Zika
      virus, and Ebola virus down to several copies. This platform also simultaneously
      distinguished between Middle East respiratory syndrome and human coronavirus in
      clinical specimens within 20 min. This arch-shaped multiple-target sensing assay
      can provide rapid, sensitive, and accurate diagnoses of emerging infectious
      diseases in clinical applications.

PMID- 30103156
TI  - Quick start-up and performance of microbial fuel cell enhanced with a
      polydiallyldimethylammonium chloride modified carbon felt anode.
AB  - It is of significant importance to simultaneously shorten the start-up time and
      enhance the electricity generation performance for practical application of
      microbial fuel cell (MFC). In this paper, the polydiallyldimethylammonium
      chloride (PDDA) modified carbon felt (PDDA-CF) electrode was prepared and used as
      the anode of PDDA-MFC. The anode significantly enhanced the start-up speed and
      electricity generation and dye wastewater degradation performances of the PDDA
      MFC. The start-up time of PDDA-MFC is only 9 h, which is only 7.5% that of the
      unmodified carbon felt anode MFC (CF-MFC). The charge transfer resistance, the
      maximum output voltage and the maximum output power density of PDDA-MFC were 9.7
      Omega, 741 mV and 537.8 mW m-2 respectively, which were 70.3% lower than, 1.7
      times and 3.3 times greater than those of CF-MFC respectively. In addition, the
      color and chemical oxygen demand (COD) removal rates of Reactive Brilliant Red X
      3B for PDDA-MFC reached 95.94% and 64.24% at 24 h respectively, which were 41.5%
      and 51.2% higher than those of CF-MFC respectively. Due to the electrostatic
      attraction of PDDA, the adhesion and metabolic mass transfer rate of
      exoelectrogens are accelerated, thus the PDDA-CF electrode has excellent
      electrochemical properties and bio-affinity. This paper provides a new idea to
      enhance the start-up speed and performance of MFC simultaneously.

PMID- 30103158
TI  - Label-free, spatially multiplexed SPR detection of immunoassays on a highly
      integrated centrifugal Lab-on-a-Disc platform.
AB  - As a direct, label-free method, Surface Plasmon Resonance (SPR) detection
      significantly reduces the needs for liquid handling and reagent storage compared
      to common enzyme-linked immunosorbent assays (ELISAs), thus enabling
      comprehensive multiplexing of bioassays on microfluidic sample-to-answer systems.
      This paper describes a highly integrated centrifugal Lab-on-a-Disc (LoaD)
      platform for automating the full process chain extending between plasma
      extraction and subsequent aliquoting to five parallelized reaction channels for
      quantitative SPR detection by an inexpensive smartphone camera. The entire, multi
      step / multi-reagent operation completes within less than 1 h. While the emphasis
      of this work is on the fluidic automation and parallelization by previously
      introduced, very robust event-triggered valving and buoyancy-driven centripetal
      pumping schemes, we successfully implement an immunoglobulin G (IgG) assay; by
      specific functionalization of the detection surfaces, the same disc layout can
      readily be customised for immunoassays panels from whole blood.

PMID- 30103159
TI  - Composite polymer coated magnetic nanoparticles based anode enhances dye
      degradation and power production in microbial fuel cells.
AB  - Combined power generation and waste degradation through microbial fuel cell (MFC)
      technology is emerging as an attractive solution for controlling pollution in
      water bodies. Cyanobacteria as fuel cell catalysts for such shared energy
      activities are not well studied even though these possess robust metabolic
      systems supporting exo-electrogenicity, biodegradation of toxic compounds, and
      their survival under wide environmental conditions. Herein, a dual chambered (50
      ml each) MFC assembled with Synechococcus sp. based bioanode and abiotic cathode
      for simultaneous power generation and Mordant orange dye degradation is reported.
      The anode was prepared by encrusting chemically synthesised magnetic nanoparticle
      (MNP) of size 8.4 +/- 0.2 nm with magnetization of 69 emu g-1on Toray carbon
      paper (TCP). The MNPs were encapsulated with aniline and pyrrole composite
      polymers to facilitate biofilm formation and cellular electron flow to the anode
      as confirmed by advance microscopic and voltametric techniques, respectively. The
      MFC with the dye mixed acetate produced current of 14.04 +/- 5.5 A m-3 with a
      maximum power density of 4.9 +/- 0.5 W m-3 (at cell voltage of 0.494 +/- 0.05 V),
      which was 18% higher than the control (without dye). The MFC produced a high OCP
      of 0.949 +/- 0.07 V and offered to decolorize 68.5% and degrade 89% of the dye
      following 216 h of its operation as confirmed by photometry (lambda385 nm) and LC
      MS/MS analyses, respectively. The efficient dye degradation is attributed to the
      bioanode for secreting high level of reactive oxygen species. The composite
      polymer coated MNPs anode with cyanobacterial biofilm is therefore, a highly
      efficient construct for enhanced azo dye degradation and associated power
      generation in a MFC system.

PMID- 30103160
TI  - Electrical activity of the human amygdala during all-night sleep and wakefulness.
AB  - OBJECTIVE: The aim of the present work was to characterize the dynamics of the
      human amygdala across the different sleep stages and during wakefulness. METHODS:
      Simultaneous intracranial electrical recordings of the amygdala, hippocampus, and
      scalp electroencephalography during spontaneous sleep polysomnography in four
      patients suffering from epilepsy were analyzed. RESULTS: Power spectrum of the
      amygdala revealed no differences between rapid eye movement (REM) and wakefulness
      for all frequencies except higher power at 9 Hz during wakefulness and some low
      Gamma frequencies. Conversely, higher power was observed in non-REM (NREM) sleep
      than wakefulness for Delta, Theta and Sigma. CONCLUSIONS: Our results showed
      similar activity in the amygdala between wakefulness and REM sleep suggesting
      that the amygdala is as active in REM as during wakefulness. The higher power in
      Sigma frequencies during NREM sleep suggests that amygdala slow activity may play
      a significant role during NREM in concurrence with hippocampal activity.
      SIGNIFICANCE: While studies have described the metabolic activity of the human
      amygdala during sleep, our results show the corresponding electrical pattern
      during the whole night, pointing out an increase of slow activity during NREM
      sleep that might be subjected to similar influences as other subcortical brain
      structures, such as the hippocampus.

PMID- 30103161
TI  - Specific EEG markers in POLG1 Alpers' syndrome.
AB  - OBJECTIVE: To examine whether rhythmic high-amplitude delta with superimposed
      (poly)spikes (RHADS) in EEG allow a reliable early diagnosis of Alpers
      Huttenlocher syndrome (AHS) and contribute to recognition of this disease.
      METHODS: EEGs of nine patients with DNA-proven AHS and fifty age-matched patients
      with status epilepticus were retrospectively examined by experts for the presence
      of RHADS and for accompanying clinical signs and high-frequency ripples.
      Reproducibility of RHADS identification was tested in a blinded panel. RESULTS:
      Expert defined RHADS were found in at least one EEG of all AHS patients and none
      of the control group. RHADS were present at first status epilepticus in six AHS
      patients (67%). Sometimes they appeared 5-10 weeks later and disappeared over
      time. RHADS were symptomatic in three AHS patients and five AHS patients showed
      distinct ripples on the (poly)spikes of RHADS. Independent RHADS identification
      by the blinded panel resulted in a sensitivity of 87.5% (95% CI 47-100) and a
      specificity of 87.5% (95% CI 77-94) as compared to the experts' reporting.
      CONCLUSION: RHADS are a highly specific EEG phenomenon for diagnosis of AHS and
      can be reliably recognized. Clinical expression and EEG ripples suggest that they
      signify an epileptic phenomenon. SIGNIFICANCE: RHADS provide a specific tool for
      AHS diagnosis.

PMID- 30103162
TI  - History of matrix genes mutations within PCR target regions among circulating
      influenza H3N2 clades over ten-plus-years.
AB  - BACKGROUND: Emerging influenza A/H3N2 clades have been associated with M1 gene
      mutations which affect the performance of commercial PCR assays. OBJECTIVES AND
      STUDY DESIGN: The evolution and prevalence of problematic M1 mutations, and their
      associated viral clades, were investigated. All European and USA isolates from
      the GISAID database with both HA and M1 sequences available, collected during the
      respiratory seasons from the Fall of 2007 through January of 2018, were analyzed.
      RESULTS: Five M1 target region patterns, designated A-E, were observed in more
      than 10% of the isolates during a season, with patterns that appeared
      sequentially, each having one additional mutation. The C153T mutation was
      universal. Pattern A, which only had the single mutation, predominated between
      2007/08 and 2009/10. Dual- and triple-mutation patterns (B and C) emerged in
      2010/11 and 2011/12 respectively, and pattern C predominated for one season
      (2012/13). In 2012/13, the problematic quadruple-mutation containing C163T first
      appeared in 3C.2 viruses. Seasons 2013/14 and 14/15 were associated with
      significant viral diversity with five clades and four M1 patterns co-circulating,
      with different rates in Europe and the USA. Since 2014, clade 3C.2a with M1
      pattern D has emerged as the predominant type. During 2016/17 season, a new
      quintuplet mutation pattern (E) emerged in cluster 3C.2a1 isolates. CONCLUSIONS:
      M1 target region mutations have been prevalent for more than ten years, with the
      number of mutations continually increasing. Often population inferences of M1
      mutations can be made based on viral clade. However, gene segment reassortment
      can affect predictive abilities.

PMID- 30103163
TI  - Cellular DNA quantification in respiratory samples for the normalization of viral
      load: a real need?
AB  - BACKGROUND: Respiratory tract infections have an enormous social economic impact,
      with high incidence of hospitalization and high costs. Adequate specimen
      collection is the first crucial step for the correct diagnosis of viral
      respiratory infections. OBJECTIVES: The present retrospective study aimed: i) to
      verify the cell yield obtained from sampling the nasal respiratory tract using
      mid-turbinate flocked swabs; ii) to evaluate the normalization of viral load,
      based on cell number; and iii) to compare the kinetics of viral infection
      obtained with normalized vs non-normalized viral load. STUDY DESIGN: The number
      of cells were quantified by real-time PCR in residual extract of nasal swabs
      tested for respiratory viruses detection and stored at -80  degrees C in a
      universal transport medium (UTMTM). RESULTS: A total of 513 virus-positive and
      226 virus-negative samples were analyzed. Overall, a median of 4.42 log10 beta2
      microgolubin DNA copy number/ml of UTMTM (range 1.17-7.26) was detected. A
      significantly higher number of cells was observed in virus-positive as compared
      to virus-negative samples (4.75 vs 3.76; p < 0.001). Viral loads expressed as
      log10 RNA copies/ml of UTMTM and log10 RNA copies/median number of cells were
      compared in virus-positive samples and a strict correlation (r = 0.89, p < 0.001)
      and agreement (R2 = 0.82) were observed. In addition, infection kinetics were
      compared using the two methods with a follow-up series of eight episodes of viral
      infection and the mean difference was -0.57 log10 (range -1.99 to 0.40).
      CONCLUSIONS: The normalization of viral load using cellular load compliments the
      validation of real-time PCR results in the diagnosis of respiratory viruses but
      is not strictly needed.

PMID- 30103164
TI  - Chalcone derivatives from the root bark of Morus alba L. act as inhibitors of
      PTP1B and alpha-glucosidase.
AB  - As part of our continuing research to obtain pharmacologically active compounds
      from Morus alba L. (Moraceae), four Diels-Alder type adducts (DAs) [morusalbins A
      D], one isoprenylated flavonoid [albanin T], together with twenty-one known
      phenolic compounds were isolated from its root bark. The chemical structures were
      established using NMR, MS, and ECD spectra. The DAs including morusalbins A-D,
      albasin B, macrourin G, yunanensin A, mulberrofuran G and K, and albanol B
      exhibited strong inhibitory activities against both protein tyrosine phosphatase
      1B (PTP1B) (IC50, 1.90-9.67 MUM) and alpha-glucosidase (IC50, 2.29-5.91 MUM). In
      the kinetic study, morusalbin D, albasin B, and macrourin G showed noncompetitive
      PTP1B inhibition, with Ki values of 0.33, 1.00, and 1.09 MUM, respectively. In
      contrast, these DAs together with yunanensin A produced competitive inhibition of
      alpha-glucosidase, with Ki values of 0.64, 0.42, 2.42, and 1.19 MUM,
      respectively. Furthermore, molecular docking studies revealed that these active
      DAs have high affinity and tight binding capacity towards the active site of
      PTP1B and alpha-glucosidase.

PMID- 30103165
TI  - Integrated process for scalable bioproduction of glycolic acid from cell
      catalysis of ethylene glycol.
AB  - Glycolic acid (GA) is presently booming as a versatile raw material in the fields
      of high-grade cosmetics, polymer degradable materials, and drug production. The
      biocatalysis of ethylene glycol (EG) to GA is promising, with environmentally
      friendly benefits, while the effective and straight bioproduction of GA qualified
      for polymer synthesis purity is a challenge. In this study, we combine whole cell
      catalysis step and acidification-purification step. A compressed oxygen supply in
      the sealed aerated stirred tank reaction (COS-SSTR) and a weak basic anion
      exchange resins were integrated to develop an efficient process of GA
      bioproduction from EG. Finally, 110.5 g/L of GA was obtained at the yield of
      94.4% and the volume productivity of 2.3 g/L/h in 48 h that presently is the
      greatest level for GA bioproduction. After 335 resins treatment of 5.0 L
      catalyzed broth containing 497.2 g EG, we obtained 575.4 g GA at the recovery
      rate of 98.9%.

PMID- 30103166
TI  - Effects of C/N ratio and earthworms on greenhouse gas emissions during
      vermicomposting of sewage sludge.
AB  - The emissions of greenhouse gases (CO2, CH4, and N2O) during bio-stabilization of
      sewage sludge under different C/N ratios with/without Eisenia fetida were
      evaluated in this study. Vermicomposting led to the more significant reductions
      of pH, TOC and C/N ratio compared to the control treatment without earthworms.
      C/N ratio had a significant effect on the emission of N2O, whereas its influences
      on CO2 or CH4 emission were not obvious. Earthworms reduced the CH4 emission
      greatly, although the CO2 emission was not affected by earthworms. Furthermore, a
      higher emission of N2O was observed in vermicomposting compared to the control.
      Both the C/N ratios and earthworms exerted statistically significant effects on
      the total GHG emission. Vermicomposting could enhance the degradation of organics
      and accelerate the mineralization process of nitrogen, whereas the increase in
      the C/N ratio could reduce GHG emission during vermicomposting of sewage sludge.

PMID- 30103167
TI  - Intensified bioleaching of chalcopyrite by communities with enriched ferrous or
      sulfur oxidizers.
AB  - The chalcopyrite bioleaching by enriched ferrous or sulfur oxidizers was
      investigated. The bioleaching was also intensified three times by the enriched
      communities. The results indicated that copper recoveries extracted by the
      enriched ferrous and sulfur oxidizers (Fe-O and S-O) were 38.87% and 43.13%,
      compared with that by the original community (35.35%). The positive effects of re
      introducing S-enriched community to Fe-O and S-O groups were observed with copper
      extraction rates up to 41.67% and 46.45%. CCA indicated that the community
      dynamics intensified by S-enriched community was closer to that of the no re
      inoculated one, but the Fe-enriched community drove a great fluctuation. A
      mechanism model for S-enriched community intensifying chalcopyrite bioleaching
      was proposed. More sulfur oxidizers in community slowed down jarosite formation
      and maintained lower ORP, which was propitious to chalcopyrite dissolution.
      Meanwhile, they accelerated S0 decomposition and decreased pH, which promoted
      acid leaching of chalcopyrite at a low cost.

PMID- 30103168
TI  - Efficiency of dilute sulfuric acid pretreatment of distillery stillage in the
      production of cellulosic ethanol.
AB  - The aim of this study was to examine suitability of distillery stillage of
      various origins subjected to dilute sulfuric acidic pretreatment for production
      of cellulosic ethanol. Optimal conditions for dilute acid pretreatment of: rye
      and wheat distillery stillage 121  degrees C, 0.2 M H2SO4, 60 min; maize stillage
      131  degrees C, 0.2 M H2SO4, 60 min. The highest efficiency of enzymatic
      hydrolysis was achieved for rye and wheat stillage using 1 g of DW and the
      concentration of cellulolytic enzyme of 24% w/w, and for maize stillage 3 g of DW
      and enzyme concentration of 24% w/w. The use of rye and wheat stillage for
      production of ethanol does not require a detoxification process and enables full
      attenuation of glucose after 48 h of the process. However, the use of maize
      stillage as a raw material must be preceded by a detoxification process that
      guarantees a reduction of 5-hydroxymethylfurfural concentration in the
      fermentation medium.

PMID- 30103169
TI  - Using the radioligand-receptor binding assay for paralytic shellfish toxins: A
      case study on shellfish from Morocco.
AB  - Paralytic shellfish poisoning (PSP) events occur regularly along the
      Mediterranean and Atlantic coast of Morocco, and have been responsible for
      several severe cases of human intoxication. Along the southern Atlantic coast of
      Morocco, aquaculture and intensive artisanal fishing practices have recently been
      particularly heavily impacted, and toxic species have been observed in increasing
      intensity and frequency. In the 1990's a regulatory monitoring program was
      established for the coastal waters off Morocco by the National Institute of
      Fisheries Research (INRH), to reduce the risk of intoxication with biotoxins. The
      regulatory monitoring is conducted weekly and includes toxic phytoplankton
      enumeration and identification, as well as saxitoxin (STX) analysis in seafood
      using the mouse bioassay (MBA). Animal testing remains the most widely used
      screening method for PSP toxin detection, yet its use is being reconsidered for
      animal-related ethical issues, as well as for practical considerations. To be
      able to better evaluate alternatives to animal testing, the performance of a
      nuclear-based radioligand-receptor binding assay (RBA) for paralytic shellfish
      toxins was assessed and compared with the MBA using four commercially important
      shellfish matrices, including cockles Cerastoderma edule, razor shells Solen
      marginatus, oysters Crassostrea gigas, and mussels Perna perna. Over 50 samples
      were collected and analysed as part of the regulatory monitoring framework
      including a suite of monthly samples from 2017 and all samples identified as
      toxic by MBA since 2011. Testing of reference material and evaluation of assay
      critical parameters (e.g. slope of calibration curve, internal quality control QC
      and IC50) confirmed the robustness of the RBA methodology. With this RBA method,
      STX-like activity detected in shellfish samples ranged from 33 to 8500 MUg STX
      equivalents per kg. RBA data were significantly correlated (P < 0.0001, Pearson r
      = 0.96) with the MBA-derived dataset. Importantly, the RBA method allowed for the
      detection and quantification of PSP toxins at levels not detectable by using the
      mouse bioassay. The limits of quantification of the RBA was calculated and found
      to be 10-fold lower than that of the MBA, respectively 35.24 +/- 5.99 and 325 MUg
      STX equivalents per kg of tissue. In addition, the RBA was easier to use and
      produced reliable results more rapidly than the MBA and without use of live
      animals. Considering the increasing risks associated with harmful algal blooms,
      globally and in Morocco, together with the increased development of aquaculture
      production and seafood consumption and the difficulties of live animal testing,
      these findings indicate that the RBA method is a reliable and effective
      alternative to the MBA method.

PMID- 30103170
TI  - Metronomic oral doxorubicin in combination of Chk1 inhibitor MK-8776 for p53
      deficient breast cancer treatment.
AB  - Metronomic chemotherapy, which is defined as a low-dose and frequent
      administration of cytotoxic drugs without drug-free breaks, has been recently
      emerged as an alternative to traditional MTD therapy and has shown therapeutic
      benefit in breast cancer patients in numbers of clinical studies. Unlike MTD,
      metronomic chemotherapy acts by multiple mechanisms including antiangiogenic
      effect and immunomodulation, but the direct cytotoxic effect only playing a minor
      role due to the lowered dose. In this light, within the limits of p53-deficient
      breast cancer, we demonstrate the enhanced anticancer effect of metronomic
      chemotherapy using doxorubicin when combined with Chk1 inhibitor MK-8776 by
      specifically augmenting the direct cytotoxic effect on cancer cells. Since the
      oral drug is greatly favored in metronomic chemotherapy due to the frequent and
      potential long-term administration, we prepared an oral doxorubicin by producing
      an ionic complex with deoxycholic acid, which showed sufficient bioavailability
      and anticancer effect when administered orally. MK-8776 selectively enhanced the
      cytotoxic effect of low-concentration doxorubicin in p53-deficient breast cancer
      cells by abrogating the Chk1-dependent cell cycle arrest in vitro. Consistently,
      combining MK-8776 significantly improved the anticancer effect of the daily
      administered oral doxorubicin in p53-deficient breast cancer xenografts
      especially in a lower dose of doxorubicin without evident systemic toxicities.
      Combination therapy of MK-8776 and metronomic oral doxorubicin would be thus
      promising in the treatment of p53-deficient breast cancer benefited from the
      augmented direct cytotoxic effect and low risk of toxicities.

PMID- 30103171
TI  - Amino acid-based Poly(ester urea) copolymer films for hernia-repair applications.
AB  - The use of degradable materials is required to address current performance and
      functionality shortcomings from biologically-derived tissues and non-resorbable
      synthetic materials used for hernia mesh repair applications. Herein a series of
      degradable l-valine-co-l-phenylalanine poly(ester urea) (PEU) copolymers were
      investigated for soft-tissue repair. Poly[(1-VAL-8)0.7-co-(1-PHE-6)0.3] showed
      the highest uniaxial mechanical properties (332.5 +/- 3.5 MPa). Additionally, l
      valine-co-l-phenylalanine poly(ester urea)s were blade coated on small intestine
      submucosa extracellular matrix (SIS-ECM) and found to enhance the burst test
      mechanical properties of SIS-ECM in composite films (force at break between 102.6
      +/- 6.5-151.4 +/- 11.3 N). Free standing films of l-valine-co-l-phenylalanine
      PEUs were found to have superior extension at break when compared to SIS-ECM
      (averages between 1.2 and 1.9 cm and 1.2 cm respectively). Fibroblast (L-929)
      spreading, proliferation, and improved attachment over control were observed
      without toxicity in vitro, while a reduced inflammatory response at both 7 and 14
      days post-implant was observed for poly[(1-VAL-8)?0.7-co-(1-PHE-6)?0.3] when
      compared to polypropylene in an in vivo rat hernia model. These results support
      the use of PEU copolymers as free-standing films or as composite materials in
      soft-tissue applications for hernia-repair.

PMID- 30103172
TI  - A systematic critical review of physical activity aspects in clinical guidelines
      for multiple sclerosis.
AB  - OBJECTIVE: This paper aims to evaluate the quality of clinical guidelines (CGs)
      for MS and to critically appraise physical activity-related recommendations. DATA
      SOURCES: Medical databases (MEDLINE, TRIP), clearinghouses, and guideline
      developers. An expert was asked to confirm if the list of CGs was complete. STUDY
      SELECTION: Evidence-based CGs specific to MS with recommendations including
      aspects of rehabilitation or physical activity were included. DATA EXTRACTION:
      Two reviewers independently first assessed the methodological quality of the CGs
      based on the 23 items of the Appraisal of Guidelines for Research and Evaluation
      Instrument version two (AGREE II) and second evaluated the physical activity
      related content quality using an instrument containing 14 items that was used for
      the development of the National Recommendations for Physical Activity in Germany.
      DATA SYNTHESIS: For the AGREE II domains and the criteria for content quality,
      standardized domain scores were calculated. RESULTS: Three CGs were included. The
      average scores for the methodological quality of the domains were: scope and
      purpose (91%), stakeholder involvement (81%), rigor of development (78%), clarity
      of presentation (93%), applicability (53%), and editorial independence (83%). The
      mean scores for physical activity-related content quality did not exceed 56% for
      any criteria. CONCLUSIONS: Overall, this critical review shows that the
      methodological quality of CGs were moderate to good but physical activity-related
      content quality was heterogeneous and low. Results emphasize the need for more
      specific physical activity recommendations that incorporate multiple aspects of
      physical activity prescription.

PMID- 30103173
TI  - Association between brain atrophy and cognitive motor interference in multiple
      sclerosis.
AB  - INTRODUCTION: Cognitive motor interference (CMI) is performance impairment due to
      simultaneuous task execution and is measured using the dual task cost (DTC). No
      pathological feature of MS has to date been associated with CMI. AIM: To assess
      the relationship between brain volumes and CMI, as measured using the DTC, in a
      cross-sectional study. METHODS: A group of persons with MS (pwMS) and an age- and
      sex-matched healthy control (HC) group underwent 3D gait analysis during using
      the dual task paradigm. Brain volumes were measured on T1-weighted gradient echo
      scans using SIENAX software. The relationships between brain volumes and the DTCs
      of spatial temporal parameters were evaluated using Pearson correlation. A
      multiple regression model was used to evaluate the ability to predict the DTC of
      cadence based on brain volume and grey matter (GM) volume. RESULTS: Forty-four
      patients and 16 HCs underwent MRI and gait analysis. The mean expanded disability
      status scale (EDSS) was 2.4 +/- 1.5. Significant relationships between brain
      volumes and DTC were found only in the pwMS group, with higher rho scores for the
      DTC of mean velocity, DTC of cadence, and DTC of stride time. A statistically
      significant regression equation with an R2 value of 0.684 was found using GM and
      Z-score on the Stroop test as predictors of the DTC of cadence (p < 0.001).
      CONCLUSION: Brain atrophy, especially than in the GM, is a major determinant of
      DTC, although other pathological markers also contribute to CMI in patients with
      MS.

PMID- 30103174
TI  - Glutamate heteroreceptor complexes in the brain.
AB  - The existence of mGluR, NMDAR, AMPAR and putative KAR heteroreceptor complexes in
      synaptic and extrasynaptic regions of brain glutamate synapses represents a major
      integrative mechanism. Our aim in the current article is to analyze if the
      formation of the different types glutamate hetereceptor complexes involves the
      contribution of triplet amino acid homologies (protriplets) in a postulated
      receptor interface based on the triplet puzzle theory. Seven main sets (lists) of
      receptor pairs in databases were used containing various sets (lists) of human
      receptor heteromers and nonheteromers obtained from the available scientific
      publications including the publically available GPCR-hetnet database. Brain
      mGluR1-mGluR5 and mGluR2-mGluR4 isoreceptor complexes were demonstrated with a
      predominant extrasynaptic localization at a post- and prejunctional localization.
      The existence of putative mGluR4-mGluR7 heteroreceptor complexes in the basal
      ganglia is proposed. Metabotropic glutamate receptor subtypes also participated
      in the formation of a large number of heteroreceptor complexes like mGluR1-A1R,
      mGluR5-A2AR, mGluR5-D2R and D2R-A2AR-mGluR5, located in relation to glutamate
      synapses, especially in the basal ganglia. A putative mGluR1-GABAB1/2
      heterocomplex may also exist. NMDAR heteroreceptor complexes were also
      demonstrated as a fundamental integrative mechanism in the glutamate synapse and
      its extrasynaptic membranes. It represented fundamental work on inter alia NMDAR
      mGluR5, NMDAR-D1R and NMDAR-D2R heteroreceptor complexes involving both
      antagonistic and facilitatory allosteric receptor-receptor interactions. As to
      AMPA receptors, a heterocomplex was found for the interaction between IFNgR1 and
      the AMPAR mediated via the subunit GluA1 which may be of relevance for
      neuroinflammation. AMPAR-D2R heteroreceptor complexes were also demonstrated.
      Besides glutamate heteroreceptor complexes and their allosteric receptor-receptor
      interactions, a significant mechanism for the functional crosstalk can also be
      phosphorylation and/or reorganization of adapter proteins with dynamic binding to
      the two receptors modulating the allosteric receptor mechanism.

PMID- 30103175
TI  - Effect of long-term administration of ranitidine, a histamine H2 receptor
      antagonist, on bone metabolism in young growing rats.
AB  - BACKGROUND: Histamine regulates function of osteoclasts and osteoblasts, however
      data regarding the influence of histamine H2 receptors antagonists on bone tissue
      are ambiguous. Factors that influence growing skeleton may have an important
      impact on the peak bone mass and future risk of fractures. The aim of our study
      was the assessment of influence of ranitidine, on growing bones. METHODS: The
      experiment was carried out on young male Wistar rats divided into two groups
      receiving either ranitidine (10mg/kg ip) or vehicle. RESULTS: A significant
      decrease in femoral BMD in ranitidine-treated rats (R) compared to vehicle
      treated ones (C) was detected (0.262+/-0.009g/cm2vs. 0.271 +/-0.007g/cm2,
      p<0.05). In group R we observed elevated serum C-terminated telopeptide of type I
      collagen (CTX) level with concomitantly lowered serum osteocalcin (OC)
      concentration comparing to control group (151.2+/-27.2pg/ml vs. 101.5+/-55.6,
      p<0.05 and 229.1+/-50.0pg/ml vs. 292.0+/-52.9, p<0.05, respectively). Serum
      concentration of inorganic phosphorus was lower in group R than in group C (134+/
      13mmol/L vs. 157+/-28mmol/L, p<0.05). CONCLUSIONS: Long-term administration of
      ranitidine increases bone resorption and decreases bone formation in growing rats
      leading to decrease in BMD.

PMID- 30103176
TI  - Bupropion attenuates morphine tolerance and dependence: Possible role of
      glutamate, norepinephrine, inflammation, and oxidative stress.
AB  - BACKGROUND: Morphine - the main pillar of nociceptive pain management - systemic
      use is associated with development of tolerance and dependence. Tolerance and
      dependence lay a heavy burden in clinical pain management settings. An added
      weight to this dilemma is that effective, safe, and tolerable solution to this
      problem is still beyond reach. Antidepressants were reported as possible
      alleviators of opioid tolerance and dependence. One of the increasingly used
      antidepressant in clinical practice is bupropion given its high safety and
      tolerability profile. METHODS: The study was performed on male Balb-c mice
      weighing 20-30g. Hot plate test was used for assessment of bupropion (5mg/kg, ip)
      possible analgesic activity and enhancement of morphine acute analgesia (1 and
      5mg/kg, sc). Repeated morphine (5mg/kg, sc) administration for 9days developed
      tolerance and dependence, bupropion (5mg/kg, ip) was concurrently administered to
      evaluate its potential to modulate these processes. We also biochemically
      analyzed bupropion effect on these phenomena through modulation of
      neurotransmitters (glutamate and norepinephrine), inflammatory status (nitric
      oxide), and pro-antioxidant balance (malondialdehyde and reduced glutathione).
      RESULTS: Bupropion was devoid of intrinsic analgesic activity and did not enhance
      morphine acute analgesia. However, bupropion significantly attenuated morphine
      tolerance and dependence development and abstinence syndrome with corresponding
      suppression of morphine induced changes in glutamate, norepinephrine,
      inflammatory status, and prooxidant-antioxidant balance. CONCLUSION: Bupropion
      efficacy in attenuation of morphine tolerance and dependence with its high safety
      and tolerability profile provide an alternative option to conventional agents
      e.g., ketamine and clonidine to modulate these phenomena.

PMID- 30103177
TI  - Vertical drop jump landing depth influences knee kinematics in female
      recreational athletes.
AB  - OBJECTIVES: To examine whether different vertical drop jump (VDJ) landing depth
      (small versus deep) and stance width (wide versus narrow) may alter movement
      biomechanics in female recreational athletes. The purpose was also to identify
      whether leg muscle strength is a predictive factor for knee control during a VDJ.
      DESIGN: Cross-sectional. SETTING: Biomechanics laboratory. PARTICIPANTS: Eighteen
      women aged between 18 and 30 years. MAIN OUTCOME MEASURES: Three VDJ tests were
      used for biomechanical analysis: 1) small "bounce" jump (BJ), 2) deep
      "countermovement" jump with wide (CMJW) and 3) narrow foot position (CMJN).
      Subjects also performed an isometric knee-extension strength test, dichotomized
      to 'weak' versus 'strong' subjects according to median and quartiles. RESULTS:
      There were greater knee valgus angles during landing for both the CMJW and CMJN
      test compared to the BJ test (p <= 0.05). Differences in knee valgus between weak
      and strong subjects were significant for the BJ test (p = 0.044) but not for any
      of the other tests. CONCLUSIONS: VDJ landing depth influences knee kinematics in
      women. Landing depth may therefore be considered when screening athletes using
      the VDJ test. Also, muscle strength seems to influence the amount of knee valgus
      angles, but the difference was not statistically significant (except for the BJ
      test) in this small cohort.

PMID- 30103178
TI  - Thermosensitive biomimetic polyisocyanopeptide hydrogels may facilitate wound
      repair.
AB  - Changing wound dressings inflicts pain and may disrupt wound repair. Novel
      synthetic thermosensitive hydrogels based on polyisocyanopeptide (PIC) offer a
      solution. These gels are liquid below 16  degrees C and form gels beyond room
      temperature. The architecture and mechanical properties of PIC gels closely
      resemble collagen and fibrin, and include the characteristic stiffening response
      at high strains. Considering the reversible thermo-responsive behavior, we
      postulate that PIC gels are easy to apply and remove, and facilitate healing
      without eliciting foreign body responses or excessive inflammation.
      Biocompatibility may be higher in RGD-peptide-functionalized PIC gels due to
      enhanced cell binding capabilities. Full-thickness dorsal skin wounds in mice
      were compared to wounds treated with PIC gel and PIC-RGD gel for 3 and 7 days. No
      foreign body reactions and similar wound closure rates were found in all groups.
      The level of macrophages, myofibroblasts, epithelial migration, collagen
      expression, and blood vessels did not significantly differ from controls.
      Surprisingly, granulocyte populations in the wound decreased significantly in the
      PIC gel-treated groups, likely because foreign bacteria could not penetrate the
      gel. RGD-peptides did not further improve any effect observed for PIC. The
      absence of adverse effects, ease of application, and the possibilities for bio
      functionalization make the biomimetic PIC hydrogels suitable for development into
      wound dressings.

PMID- 30103179
TI  - Complex suicides: A review of the literature with considerations on a single case
      of abdominal self stabbing and plastic bag suffocation.
AB  - Complex suicides are rare and consist in the use of more than one method to
      induce death, representing a challenging investigation for forensic pathologists.
      According to the several combinations reported in literature, they have been
      classified into "typical" (where two common suicide methods are associated) and
      "atypical" (where more than two methods, or infrequent combinations of suicide
      methods are involved). In the case discussed here, an elderly man suffering of
      depression was found dead inside the tool shed of his house with a knife embedded
      in the abdomen and two plastic bags fastened around the neck using a twine. Three
      other superficial stab wounds were clustered close to the penetrating lesion.
      Internal examination revealed haemorrhagic infiltration at the mesentery and
      haemoperitoneum. No evident signs of asphyxia were highlighted and the cause of
      death was attributed to haemorrhagic shock. This association of suicide methods
      has turned out to be unusual. A review of the literature concerning complex
      suicides, abdominal self-stabbing and plastic bag suffocation has been managed.
      Crime scene and details of the used tools, medical and psychiatric history of the
      victim and features of the internal and external lesions have been examined and
      compared to previous studies. Toxicological analyses were not performed.

PMID- 30103180
TI  - Predicting body movements for person identification under different walking
      conditions.
AB  - Human motion during walking provides biometric information which can be utilized
      to quantify the similarity between two persons or identify a person. The purpose
      of this study was to develop a method for identifying a person using their
      walking motion when another walking motion under different conditions is given.
      This type of situation occurs frequently in forensic gait science. Twenty-eight
      subjects were asked to walk in a gait laboratory, and the positions of their
      joints were tracked using a three-dimensional motion capture system. The subjects
      repeated their walking motion both without a weight and with a tote bag weighing
      a total of 5% of their body weight in their right hand. The positions of 17
      anatomical landmarks during two cycles of a gait trial were generated to form a
      gait vector. We developed two different linear transformation methods to
      determine the functional relationship between the normal gait vectors and the
      tote-bag gait vectors from the collected gait data, one using linear
      transformations and the other using partial least squares regression. These
      methods were validated by predicting the tote-bag gait vector given a normal gait
      vector of a person, accomplished by calculating the Euclidean distance between
      the predicted vector to the measured tote-bag gait vector of the same person. The
      mean values of the prediction scores for the two methods were 96.4 and 95.0,
      respectively. This study demonstrated the potential for identifying a person
      based on their walking motion, even under different walking conditions.

PMID- 30103181
TI  - Anxiety, depression, and anger in functional gastrointestinal disorders: A Cross
      sectional observational study.
AB  - Previous studies have identified a link between anger and somatization. However,
      little is known about the associations between anger and the development and
      progression of Functional Gastrointestinal Disorders (FGID). The study aim was to
      determine the associations between FGID and anger, anxiety, and depression.
      Participants in this cross-sectional observational study were 109 consecutive
      patients aged 18-64 years with FGID at Gastroenterology Clinic of Baskent
      University Hospital. A control group comprised of 96 individuals with no chronic
      gastrointestinal disorders recruited via snowball sampling. Sociodemographic and
      clinical information were obtained and participants completed the Hospital
      Anxiety and Depression Scale and the State-Trait Anger Expression Inventory-2.
      FGID participants scored higher than controls on depression, anxiety, state
      anger, and anger expression-in. When the FGID group was divided into upper and
      lower gastrointestinal symptom groups, the lower symptom group showed higher
      anger expression-out scores than the upper symptom group. Anger may contribute to
      the etiology and development of FGID. This is the first study to demonstrate a
      significant psychological difference between individuals with lower and upper
      FGID. Interdisciplinary collaboration with gastroenterologists and psychiatrists
      could strengthen FGID evaluation and may improve treatment compliance.

PMID- 30103182
TI  - Health risk behaviors and psychological problems among South Korean, North
      Korean, and other multicultural family adolescents (2011-2016).
AB  - This study was aimed to investigate the health risk behaviors and psychological
      problems among North Korean, other multicultural, and South Korean family
      adolescents. The data were collected from the Korea Youth Risk Behavior web-based
      survey (2011-2016) data set. A total of 17,195 adolescents (mean age 14.65 +/-
      0.01 years) were analyzed to compare health risk behaviors and psychological
      problems among the three groups. Concerning risk behaviors, multicultural family
      adolescents showed a higher rate of alcohol use, smoking, drug use and sexual
      relations compared to South Korean family adolescents. Moreover, North Korean
      family adolescents were more likely to experience those risk behaviors than other
      multicultural family adolescents. Concerning psychological problems,
      multicultural family youth displayed more depressed mood, and more suicidal
      ideation, planning, and attempts when compared with South Korean family youth.
      Among multicultural families, North Korean family adolescents were more depressed
      and showed higher suicidality. School-based education and preventive
      interventions are necessary to manage risk behaviors and psychological
      difficulties of adolescents in North Korean and other multicultural families.

PMID- 30103183
TI  - Influence of socio-cultural factors on the emotional problems among college going
      young-adult children of parents with alcoholism: A study from South India.
AB  - Young-adult children of parents with alcoholism are vulnerable to anxiety and
      depression. We studied the prevalence of emotional psychopathology and examined
      the mediating role of environmental factors (family support, community support
      and participation in religious rituals) in relation to psychopathology. College
      students (N = 1555), aged 18-24 years, from urban and rural domicile were
      screened on Children of Alcoholics Screening Test (CAST) and those who were
      positive were assessed for emotional psychopathology on Depression, Anxiety and
      Stress Scale (DASS-21). Young-adult children of alcoholics with emotional
      psychopathology were compared with those without emotional psychopathology on
      demographic characteristics, quality of life, and a questionnaire which measured
      the role of socio-cultural factors. 33% (N = 512) of 1555 participants screened
      were found to be Young-adult children of alcoholics. Among them, 35% (N = 181)
      reported experiencing emotional psychopathology. Participants with high emotional
      psychopathology reported receiving less support from the family (8.44 +/- 1.19 vs
      9.57 +/- 1.26, p = 0.003), community (6.97 +/- 1.08 vs 8.88 +/- 1.19, p = 0.001);
      they participated less in religious rituals (5 +/- 0.18 vs 6.56 +/- 0.41, p =
      0.008) compared to those without psychopathology. Quality of life was
      significantly lower among Young-adult children of alcoholics with emotional
      psychopathology. A considerable proportion of Young-adult children of alcoholics
      reported emotional psychopathology and their quality of life was poor. The
      modifiable socio-cultural factors such as family, community support and
      participation in religious rituals were associated with emotional
      psychopathology. A better utilization of these factors may mitigate the burden of
      emotional psychopathology and improve quality of life in this vulnerable group.

PMID- 30103184
TI  - Etizolam withdrawal catatonia: The first case report.

PMID- 30103185
TI  - Perceived stigma and its correlates among treatment seeking alcohol and opioid
      users at a tertiary care centre in India.
AB  - BACKGROUND AND AIMS: Perceived stigma is related to the beliefs that members of
      stigmatized group have about the stigmatizing attitudes present in society. We
      present the data on perceived stigma in alcohol and opioid users seeking
      treatment. METHODS: This study was conducted at a tertiary care de-addiction
      facility with recruitment of patients with substance use disorders (alcohol and
      opioid use). Perceived stigma was assessed using Perceived Stigma of Substance
      Abuse Scale (PSAS). RESULTS: The study included 201 participants, majority of
      whom were males (99.5%), educated up to 10th std. (65.7%), with mean duration of
      substance use of 11.4 years. Opiates were the primary substance of abuse in the
      majority (83.6%) with ever-injecting drug use present in a considerable
      proportion (29.4%). The mean perceived stigma scale score was 21.23 +/- 3.03. The
      perceived stigma was higher in patients from rural background, but was not
      associated with age, educational status, current living situation, duration of
      substance use and injecting drug use. CONCLUSION: Stigma remains an important
      issue among patients with alcohol and opioid use disorders. Perceived stigma
      could affect participation in society and health seeking behavior in substance
      using population, thus needs further exploration.

PMID- 30103186
TI  - Biophysical control of the cell rearrangements and cell shape changes that build
      epithelial tissues.
AB  - Epithelial cell rearrangements and cell shape changes are fundamental mechanisms
      by which cells build and shape elaborate and diverse tissue architectures from
      simple tissue sheets. These cell behaviors are regulated by a complex interplay
      between physical and biochemical mechanisms, many of which have been uncovered in
      recent studies in Drosophila. While the regulation of these cell behaviors is
      still under investigation, emerging technologies are being used to gain
      experimental control over these behaviors, opening new possibilities for
      designing and engineering tissue structures. Analysis of the biophysical
      mechanisms governing cell shape and movement will be crucial for understanding
      morphogenesis and for harnessing this knowledge to build tissues of precise
      shapes and structures for basic science and engineering applications.

PMID- 30103187
TI  - A pilot randomized clinical trial of cognitive behavioral therapy versus
      attentional bias modification for social anxiety disorder: An examination of
      outcomes and theory-based mechanisms.
AB  - No studies have compared face-to-face cognitive-behavioral therapy (CBT) and
      attention bias modification (ABM) for social anxiety disorder (SAD) and their
      purported mechanisms. We asked: 1) Is CBT more effective than ABM? and 2) Are
      changes in attentional biases and cognitions temporally related to symptom
      change? Forty-three patients were randomly assigned to 8 sessions of ABM or up to
      20 sessions of individual CBT. Intent-to-treat results revealed that CBT was
      superior to ABM in response rates and on symptom measures at endpoint, but not on
      other measures. No differences were found on measures in rates of change between
      CBT and ABM. Frequency of negative cognitions changed in both groups and negative
      beliefs changed only in CBT. Attentional bias did not change in either group.
      Cognitive changes bidirectionally correlated with symptom change in cross-lagged
      analyses in CBT, but not in ABM, suggesting a reciprocal relationship. Trial
      level bias away from negative faces was simultaneously related to symptom change
      in ABM only. Results suggest that CBT is superior to ABM when administered at
      their typical doses, but raise questions given the similar rates of change. In
      addition, results support theories of cognitive change and raise questions about
      changes in attentional biases in CBT.

PMID- 30103188
TI  - Neural correlates of phonological processing: Disrupted in children with dyslexia
      and enhanced in musically trained children.
AB  - Phonological processing has been postulated as a core area of deficit among
      children with dyslexia. Reduced brain activation during phonological processing
      in children with dyslexia has been observed in left-hemispheric temporoparietal
      regions. Musical training has shown positive associations with phonological
      processing abilities, but the neural mechanisms underlying this relationship
      remain unspecified. The present research aims to distinguish neural correlates of
      phonological processing in school-age typically developing musically trained
      children, musically untrained children, and musically untrained children with
      dyslexia utilizing fMRI. A whole-brain ANCOVA, accounting for gender and
      nonverbal cognitive abilities, identified a main effect of group in bilateral
      temporoparietal regions. Subsequent region-of-interest analyses replicated
      temporoparietal hypoactivation in children with dyslexia relative to typically
      developing children. By contrast, musically trained children showed greater
      bilateral activation in temporoparietal regions when compared to each musically
      untrained group. Therefore, musical training shows associations with enhanced
      bilateral activation of left-hemispheric regions known to be important for
      reading. Findings suggest that engagement of these regions through musical
      training may underlie the putative positive effects of music on reading
      development. This supports the hypothesis that musical training may facilitate
      the development of a bilateral compensatory neural network, which aids children
      with atypical function in left-hemispheric temporoparietal regions.

PMID- 30103189
TI  - Pyridine bioisosteres of potent GluN2B subunit containing NMDA receptor
      antagonists with benzo[7]annulene scaffold.
AB  - It has been reported that benzo [7]annulen-7-amines bearing electron withdrawing
      substituents such as 3d with a 2-Cl or 3e with a 2-NO2 moiety show very high
      affinity towards the ifenprodil binding site of GluN2B subunit containing NMDA
      receptors. Therefore, bioisosteres of 3 with an electron deficient pyridine ring
      instead of the chloro- or nitrobenzene ring were envisaged. Starting from
      pyridine-2,3-dicarboxylic acid (5) a five-step synthesis of the key intermediate,
      the ketone 10, was developed. Reductive amination with various primary amines and
      NaBH(OAc)3 led to the homologous secondary amines 11a-c. Subsequent methylation
      yielded the tertiary amines 12b and 12c. Receptor binding studies with
      [3H]ifenprodil revealed Ki-values above 100 nM for the most active phenylpropyl-
      and phenylbutylamines 11b and 11c. The >100-fold reduced GluN2B affinity of
      pyridines 11b and 11c compared to the GluN2B affinity of the corresponding chloro
      and nitrobenzene derivatives 3d and 3e indicates that the pyridine ring is not
      tolerated as bioisosteric replacement of the chloro- or nitrobenzene ring in this
      type of compounds.

PMID- 30103190
TI  - Identification of crizotinib derivatives as potent SHIP2 inhibitors for the
      treatment of Alzheimer's disease.
AB  - SH2 domain-containing inositol 5'-phosphatase 2 (SHIP2) is a lipid phosphatase
      that produce phosphatidylinositol 3,4-bisphosphate (PI(3,4)P2) from
      phosphatidylinositol 3,4,5-triphosphate (PI(3,4,5)P3), and is involved in many
      diseases such as neurodegenerative diseases. A recent report demonstrating that
      SHIP2 inhibition decreased tau hyperphosphorylation induced by amyloid beta and
      rescued memory impairment in a transgenic Alzheimer's disease mouse model
      indicates SHIP2 can be a promising therapeutic target for Alzheimer's disease. In
      the present study, we have developed novel, potent SHIP2 inhibitors by extensive
      structural elaboration of crizotinib discovered from a high-throughput screening.
      Our representative compound 43 potently inhibited SHIP2 activity as well as
      GSK3beta activation in HT22 neuronal cells. It was also shown that 43 has
      favorable physicochemical properties, especially high brain penetration.
      Considering SHIP2 is one of key signal mediators for tau hyperphosphorylation,
      our potent SHIP2 inhibitor 43 may function as a promising lead compound for the
      treatment of Alzheimer's disease.

PMID- 30103191
TI  - Design, synthesis and biological evaluation of novel naphthoquinone derivatives
      as IDO1 inhibitors.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) mediated kynurenine pathway of tryptophan
      degradation is identified as an appealing and novel target in immunotherapy for
      the treatment of cancer. In this study, a novel series of naphthoquinone
      derivatives were synthesized, characterized and evaluated for their inhibitory
      activities against IDO1, and their structure-activity relationship was
      investigated. Among them, compounds T16, T44, T47, T49, T53 and T54 displayed
      potent IDO1 inhibitory activities with IC50 values ranging between 18 and 61 nM,
      which are more potent than INCB024360 undergoing clinical trial III evaluation.
      In addition, compounds T28, T44 and T53 decreased the kynurenine levels in rat
      plasma by 30%-50%. Compounds exhibiting excellent IDO1 inhibitory activities were
      also evaluated for their inhibitory activities against tryptophan 2,3-dioxygenase
      (TDO). Of which, compound T28 (IDO1 IC50 = 120 nM) showed promising TDO
      inhibition (IC50 72 nM) and was identified as an IDO1/TDO dual inhibitor.

PMID- 30103192
TI  - 99mTc(CO)3+ labeled domain I/II-specific anti-EGFR (scFv)2 antibody fragment for
      imaging EGFR expression.
AB  - Bifunctional chelators (BFCs) are covalently linked to biologically active
      targeting molecules and radiolabeled with radiometals. Technetium-99 m (99mTc) is
      the most widely used isotope in nuclear medicine because of its excellent
      physical properties. The objective of this study was to synthesize and
      characterize a novel BFC that allows for the labeling of antibodies and antibody
      fragments using the 99mTc(CO)3+ core which forms a very stable complex with 99mTc
      in the +1 oxidation sate. This study reports the synthesis of a BFC 1
      pyrrolidinyl-2,5-dione-11-(bis((1-(carboxymethyl)-1H-imidazol-2
      yl)methyl)amino)undecanoic acid (SAAC-CIM NHS ester), and the in vitro and in
      vivo evaluation of 99mTc(CO)3-SAAC-CIM-DLO6-(scFv)2 (99mTc(CO)3-DLO6-(scFv)2), a
      domain I/II-specific anti-epidermal growth factor receptor I (anti-EGFR) antibody
      fragment. The chelator allowed radiolabeling the (scFv)2 antibody fragment in
      very mild conditions with no significant decrease in binding to EGFR.
      Radiochemical yields of >50% (radiochemical purity > 95%) of the resulting anti
      EGFR (scFv)2 immunoconjugate 99mTc(CO)3-DLO6-(scFv)2 was obtained. The
      radioimmunoconjugate was stable in histidine challenge experiments with less than
      20% transchelation at 24 h after challenge in the presence of a 1500-fold excess
      of histidine. In vivo biodistribution of 99mTc(CO)3-DLO6-(scFv)2 indicates that
      the tracer was mainly cleared via renal excretion and to a lesser extent via the
      hepatobiliary pathway. The microSPECT imaging studies performed in mice confirmed
      the in vitro affinity results. The 99mTc(CO)3-DLO6-(scFv)2 shows some promising
      properties and warrants further investigation for imaging EGFR.

PMID- 30103195
TI  - Evaluation of a lymphocyte transformation test and cytokine detection assay to
      identify phenytoin and carbamazepine provoked DRESS or SJS/TEN in epilepsy
      patients.
AB  - Phenytoin (PHE) and carbamazepine (CBZ) are first rank causative drugs that can
      induce drug rash with eosinophilia and systemic symptoms (DRESS) and Stevens
      Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Identification of anti
      epileptic drugs as a culprit drug has been problematic; hence, in vitro tests
      could be promising methods to define causative drugs without clinical risk. The
      aim of this study is to evaluate the efficacy of lymphocyte transformation tests
      (LTT) and cytokine detection assays in identifying PHE and CBZ as culprit drugs.
      Peripheral blood mononuclear cells were collected from normal, PHE/CBZ tolerance
      and PHE/CBZ hypersensitivity cohorts and utilized for cell-culture assays. LTT
      was performed and culture supernatants were subjected to multiple cytokine
      detection assays. Our study showed that LTT correlated with outcomes of Naranjo's
      assessment with statistical significance (r = 0.614). Various sensitivities of
      LTT and cytokine detection assays were demonstrated. Although both assays
      provided excellent specificity, LTT yielded higher sensitivity as compared to
      those of cytokine detection assays in both DRESS and SJS/TEN. Regardless whether
      specificity is, this is the first report to demonstrate that IL-4 detection assay
      could enhance sensitivity to identify culprit drug when it was combined with LTT
      for SJS/TEN patients or it was combined with IL-2/IFN-gamma detection assays for
      DRESS ones.

PMID- 30103193
TI  - Recent developments on synthesis and biological activities of gamma-carboline.
AB  - gamma-Carboline alkaloids are a family of natural and synthetic agents that have
      diverse bioactivities including antiviral, antibacterial, antifungal,
      antiparasitic, antitumor, anti-inflammatory, neuropharmacological activities and
      so on. They constitute an important class of pharmacologically active scaffolds
      that exhibit biological activity via diverse mechanisms. This review provides an
      update on the recent developments (2010-2017) in the synthesis and biological
      activities of these compounds. In cases where sufficient information is
      available, the mechanism and the structure-activity relationship (SAR) of
      biological activity are presented, and based on our expertise in the field and
      careful analysis of the recent literature, for the potential of gamma-carboline
      alkaloids as medicinal drugs is proposed.

PMID- 30103194
TI  - Circular RNA alterations in the Bombyx mori midgut following B. mori
      nucleopolyhedrovirus infection.
AB  - Thus far, no systematic studies have examined circRNA expression profiles in the
      silkworm following B.mori nucleopolyhedrovirus (BmNPV) infection. To explore the
      expression patterns of circRNAs in the silkworm midgut following BmNPV infection,
      circRNAs in normal midguts and BmNPV-infected midguts were analyzed by high
      throughput sequencing. A total of 353 circRNAs were significantly differentially
      expressed, of which 241 were upregulated and 112 were downregulated following
      infection. GO annotation and KEGG pathways analyses of these circRNAs showed that
      many key immunity pathways and metabolism pathways were enriched in the BmNPV
      infected midguts. The potential roles of the predicted targets of the miRNAs that
      interacted with the circRNAs showed that ubiquitin, apoptosis, and endocytosis
      signaling pathways were enriched significantly by BmNPV infection.

PMID- 30103196
TI  - Intranasal immunization of cocktail/fusion protein containing Tir along with
      DeltaG active fragment of Zot as mucosal adjuvant confers enhanced immunogenicity
      and reduces E. coli O157:H7 shedding in mice.
AB  - Ruminants are the major reservoirs of Escherichia coli O157:H7 and its fecal
      shedding mainly act as a source of entry of this pathogen into the human food
      chain. In humans, E. coli O157:H7 infection causes diarrhea, hemorrhagic colitis
      and hemolytic uremic syndrome. Intimate adherence of E. coli O157:H7 is mediated
      by Translocated intimin receptor (Tir) to which intimin binds in the host cell.
      Since E. coli O157:H7 colonizes intestinal epithelium, the mucosal vaccine has a
      potential to prevent its colonization. Zonula occludens toxin (Zot) of Vibrio
      cholerae transiently, reversibly alters epithelial tight junction structure to
      increase mucosal permeability of macromolecules via paracellular route. The C
      terminal region of Zot (DeltaG) responsible for this function could be used for
      mucosal antigen delivery. Therefore, we employed individual (Tir), cocktail
      (DeltaG + Tir), fusion protein (DeltaG-Tir) and assessed the efficacy of its
      intranasal immunization on immunogenicity and fecal shedding of E. coli O157:H7
      in streptomycin treated mouse model. Compared to control, DeltaG + Tir, DeltaG
      Tir immunized mice elicited significant antigen specific antibody titers in serum
      (IgG, IgA) and feces (IgA), whereas Tir immunized mice induced only serum IgG
      titer. Cytokine analysis revealed mixed Th1/Th2 type immune response in case of
      DeltaG + Tir, DeltaG-Tir group while that of Tir group was solely Th2 type. Tir,
      DeltaG + Tir and DeltaG-Tir immunized mice showed reduction in shedding of E.
      coli O157:H7 compared to control group. However, DeltaG-Tir immunized group
      performed better than DeltaG + Tir, Tir group in reducing fecal shedding.
      Overall, our results demonstrate that intranasal immunization of DeltaG-Tir
      induces effective systemic, mucosal, cellular immune responses and represents a
      promising mucosal subunit vaccine to prevent E. coli O157:H7 colonization.

PMID- 30103197
TI  - MicroRNA-146a protects against LPS-induced organ damage by inhibiting Notch1 in
      macrophage.
AB  - MicroRNA-146a is a well-studied microRNA participating in immune and inflammatory
      diseases, but its role in sepsis has not been investigated. Here in our study, we
      found increased level of microRNA-146a in macrophage stimulated by
      lipopolysaccharide. In addition, the mRNA level of Notch1 was also increased. Up
      regulation of microRNA-146a by miR-146a-mimic alleviated inflammatory responses
      of macrophage, for the levels of IL-1beta, IL-6 and CCL-2 were decreased, and the
      activation of NF-kappaB signaling was inhibited. The histological examination
      showed that microRNA-146a protected against organ damage in mice with
      lipopolysaccharide injection, and the level of inflammatory factors, Cr, BUN, AST
      and ALT in serum were all decreased, reflecting the alleviated inflammation and
      recovered organ function. Then predicting databases were used and Notch1 was
      predicted as one of the potential targets of microRNA-146a. Knockout of Notch1 in
      macrophage showed reduced secretion of inflammatory factors and attenuated
      activation of NF-kappaB signaling in response to lipopolysaccharide. Specifically
      knockout of Notch1 in macrophage protected mice from LPS induced organ damage and
      dysfunction. Therefore, we prove that miR-146a acts as an inhibitor of
      inflammation by targeting Notch1 in macrophage, therefore protects mice from
      organ damage in sepsis.

PMID- 30103198
TI  - Comparison of the state of Lithium-Sulphur and lithium-ion batteries applied to
      electromobility.
AB  - The market share in electric vehicles (EV) is increasing. This trend is likely to
      continue due to the increased interest in reducing CO2 emissions. The electric
      vehicle market evolution depends principally on the evolution of batteries
      capacity. As a consequence, automobile manufacturers focus their efforts on
      launching in the market EVs capable to compete with internal combustion engine
      vehicles (ICEV) in both performance and economic aspects. Although EVs are
      suitable for the day-to-day needs of the typical urban driver, their range is
      still lower than ICEV, because batteries are not able to store and supply enough
      energy to the vehicle and provide the same autonomy as ICEV. EV use mostly
      Lithium-ion (Li-ion) batteries but this technology is reaching its theoretical
      limit (200-250 Wh/kg). Although the research to improve Li-ion batteries is very
      active, other researches began to investigate alternative electrochemical energy
      storage systems with higher energy density. At present, the most promising
      technology is the Lithium-Sulphur (Li-S) battery. This paper presents a review of
      the state of art of Li-Sulphur battery on EVs compared to Li-ion ones,
      considering technical, modelling, environmental and economic aspects with the aim
      of depicting the challenges this technology has to overcome to substitute Li-ion
      in the near future. This study shows how the main drawbacks for Li-S concern are
      durability, self-discharge and battery modelling. However, from an environmental
      and economic point of view, Li-S technology presents many advantages over Li-ion.

PMID- 30103199
TI  - Water use for shale gas extraction in the Sichuan Basin, China.
AB  - This study investigates the use of water for extracting shale gas in the Sichuan
      Basin of China. Both net water use and water intensity (i.e., water use per unit
      of gas produced) of shale wells are estimated by applying a process-based life
      cycle inventory (LCI) model. The results show that the net water use and water
      intensity are around 24500 m3/well and 1.9 m3 water/104 m3 gas respectively, and
      that the fracturing and completion stage of shale gas extraction accounts for the
      largest share in net water use. A comparison shows that China's water use for
      shale gas extraction is generally higher than that of other countries. By
      considering the predicted annual drilling activities in the Sichuan Basin, we
      find that the annual water demand for shale gas development is likely to be
      negligible compared to total regional water supply. However, considering the
      water demand for shale gas extraction and the water demand from other sectors may
      make water availability a significant concern for China's shale gas development
      in the future.

PMID- 30103200
TI  - Evaluation of antibiotic oxytetracycline removal in water using a gas phase
      dielectric barrier discharge plasma.
AB  - Degradation of oxytetracycline (OTC), a primary member of antibiotics in water,
      was performed by a gas phase dielectric barrier discharge (GPDBD) plasma reactor.
      The influences of operation conditions including applied voltages, air bubbling
      rates, initial OTC concentrations and initial pH values on OTC abatement were
      investigated respectively. The results showed that the decontamination process
      can be fitted by first order kinetics, and the removal ratio and rate were
      affected obviously by those parameters. After 20 min of discharge treatment,
      approximately 93.4% of OTC was removed under the experimental conditions: applied
      voltage of 7.5 kV, air flow rate of 1.0 L/min, initial OTC concentration of 100
      mg/L, and initial pH of 5.0. In addition, TOC and COD removal efficiency reached
      43.0% and 73.7% at the original pH 9.3, respectively. Furthermore, the amounts of
      hydrogen peroxide and ozone in aqueous were quantitatively measured to evaluate
      their roles during antibiotic removal, and the main function of hydroxyl radicals
      was demonstrated by the radicals scavenger test. At last, the analyses of UV-Vis
      spectra and HPLC-MS were employed to study the OTC elimination mechanism, and the
      possible decomposition pathway was proposed based on the speculated
      intermediates.

PMID- 30103201
TI  - Combination of cabazitaxel and plicamycin induces cell death in drug resistant B
      cell acute lymphoblastic leukemia.
AB  - Bone marrow microenvironment mediated downregulation of BCL6 is critical for
      maintaining cell quiescence and modulating therapeutic response in B-cell acute
      lymphoblastic leukemia (ALL). In the present study, we have performed a high
      throughput cell death assay using BCL6 knockdown REH ALL cell line to screen a
      library of FDA-approved oncology drugs. In the process, we have identified a
      microtubule inhibitor, cabazitaxel (CAB), and a RNA synthesis inhibitor,
      plicamycin (PLI) as potential anti-leukemic agents. CAB and PLI inhibited cell
      proliferation in not only the BCL6 knockdown REH cell line, but also six other
      ALL cell lines. Furthermore, combination of CAB and PLI had a synergistic effect
      in inhibiting proliferation in a cytarabine-resistant (REH/Ara-C) ALL cell line.
      Use of nanoparticles for delivery of CAB and PLI demonstrated that the
      combination was very effective when tested in a co-culture model that mimics the
      in vivo bone marrow microenvironment that typically supports ALL cell survival
      and migration into protective niches. Furthermore, exposure to PLI inhibited SOX2
      transcription and exposure to CAB inhibited not only Mcl-1 expression but also
      chemotaxis in ALL cells. Taken together, our study demonstrates the utility of
      concomitantly targeting different critical regulatory pathways to induce cell
      death in drug resistant ALL cells.

PMID- 30103202
TI  - Clinical significance of novel SH2B3 mutations in adult Chinese acute
      lymphoblastic leukemia patients.

PMID- 30103204
TI  - From the resolution revolution to evolution: structural insights into the
      evolutionary relationships between vesicle coats and the nuclear pore.
AB  - Nuclear pores and coated vesicles are elaborate multi-component protein complexes
      that oligomerize on membranes, and stabilize or induce membrane curvature. Their
      components, nucleoporins and coat proteins, respectively, share similar
      structural folds and some principles of how they interact with membranes. The
      protocoatomer hypothesis postulates that this is due to divergent evolution from
      a common ancestor. It therefore has been suggested that nucleoporins and coat
      proteins have similar higher order architectures. Here, we review recent work
      that relied on technical advances in cryo-electron microscopy and integrative
      structural biology to take a fresh look on how these proteins form membrane coats
      in situ. We discuss the relationship between the architectures of nuclear pores
      and coated vesicles, and their evolutionary origins.

PMID- 30103203
TI  - Targeting acute myeloid leukemia CD34+ stem/progenitor cells with small molecule
      inhibitor MK-8776.

PMID- 30103205
TI  - School-based versus after-school delivery of a universal wellness programme - A
      randomized controlled multi-arm trial.
AB  - : Positive self-image and body image as well as high self-esteem and media
      literacy are considered protective factors against health-compromising
      behaviours. Investigation of the optimal setting for body image prevention
      programmes is important to maximize outcomes from such programmes. Most universal
      wellness programmes are school based and thus delivered to a "captive"
      population. Only a few reports have been published about wellness programmes
      delivered in after-school settings, and none of them compared delivery after
      school to delivery in a school-based setting. AIMS: To assess the acceptability,
      feasibility and efficacy of an interactive wellness preventive programme (In
      Favour of Myself) when delivered in a school-based setting versus an after-school
      setting. METHODS: A randomized controlled multi-arm trial with 224 adolescent
      girls aged 13-15 years old was conducted. There were 102 girls participating in
      the after-school setting and 102 girls in the school-based setting. The programme
      contained nine 90-minute lessons, delivered weekly over 2 months. An intention-to
      treat assessment was performed three times: at baseline, at the programme's
      conclusion (two months) and at follow-up (3 months). RESULTS: At programme
      termination and follow-up, the impact of In Favour of Myself was higher among
      participants in the after-school setting than in the school-based setting with
      respect to advertisement strategies, media pressure, gap between current and
      ideal body image, drive for thinness and self-esteem. CONCLUSIONS: This study
      provides support for a community-led approach to promote health behaviours, an
      approach that currently is a significant feature of health improvement policy and
      practice.

PMID- 30103206
TI  - Modelling anthelmintic resistance by extending eggCounts package to allow
      individual efficacy.
AB  - The same anthelmintic treatment can have variable efficacy on individual animals
      even if the parasite population is homogenously susceptible. An extension of the
      R package eggCounts is proposed to take individual efficacy into account using a
      Bayesian hierarchical model. A simulation study is conducted to compare the
      performance of five different methods on estimating faecal egg count reduction
      and its uncertainty interval. Simulation results showed the individual efficacy
      model offered robust inference to two different data simulation procedures with
      low root mean squared error on the reduction estimate and appropriate uncertainty
      estimates. Different methods were used to evaluate the anthelmintic resistance in
      a dataset from USA with sheep and cattle faecal egg counts, where a strong
      anthelmintic resistance was detected. Open-source statistical tools were updated
      to include the proposed model.

PMID- 30103208
TI  - ANCHORING is amodal: Evidence from a signed language.
AB  - Across languages, certain linguistic forms are systematically preferred to others
      (e.g. bla > lba). But whether these preferences concern abstract constraints on
      language structure, generally, or whether these restrictions only apply to speech
      is unknown. To address this question, here we ask whether linguistic constraints
      previously identified in spoken languages apply to signs. One such constraint,
      ANCHORING, restricts the structure of reduplicated forms (AB -> ABB, not ABA). In
      two experiments, native ASL signers rated the acceptability of novel reduplicated
      forms that either violated ANCHORING (ABA) or obeyed it (ABB). In Experiment 1,
      signers made a forced choice between ABB and ABA forms; in Experiment 2, signers
      rated signs individually. Results showed that signers prefer signs that obey
      ANCHORING over ANCHORING violations (ABB > ABA). These findings show for the
      first time that ANCHORING is operative in ASL signers. These results suggest that
      some linguistic constraints are amodal, applying to both speech and signs.

PMID- 30103207
TI  - Validation of Babesia proteasome as a drug target.
AB  - Babesiosis is a tick-transmitted zoonosis caused by apicomplexan parasites of the
      genus Babesia. Treatment of this emerging malaria-related disease has relied on
      antimalarial drugs and antibiotics. The proteasome of Plasmodium, the causative
      agent of malaria, has recently been validated as a target for anti-malarial drug
      development and therefore, in this study, we investigated the effect of
      epoxyketone (carfilzomib, ONX-0914 and epoxomicin) and boronic acid (bortezomib
      and ixazomib) proteasome inhibitors on the growth and survival of Babesia.
      Testing the compounds against Babesia divergens ex vivo revealed suppressive
      effects on parasite growth with activity that was higher than the cytotoxic
      effects on a non-transformed mouse macrophage cell line. Furthermore, we showed
      that the most-effective compound, carfilzomib, significantly reduces parasite
      multiplication in a Babesia microti infected mouse model without noticeable
      adverse effects. In addition, treatment with carfilzomib lead to an ex vivo and
      in vivo decrease in proteasome activity and accumulation of polyubiquitinated
      proteins compared to untreated control. Overall, our results demonstrate that the
      Babesia proteasome is a valid target for drug development and warrants the design
      of potent and selective B. divergens proteasome inhibitors for the treatment of
      babesiosis.

PMID- 30103209
TI  - Circ-BPTF promotes bladder cancer progression and recurrence through the miR-31
      5p/RAB27A axis.
AB  - Circ-BPTF (hsa_circ_0000799) is a novel circular RNA derived from BPTF exons.
      Although BPTF is a well-studied predecessor gene, the characteristics and
      functions of circ-BPTF have not yet been reported. Here, we show that expression
      of circ-BPTF is increased in bladder cancer (BCa) tissues and cell lines compared
      with noncancerous tissues and cell lines. Consistently, BCa patients with higher
      expression levels of circ-BPTF were found to have higher tumor grades and poorer
      prognosis. Functionally, knockdown of circ-BPTF inhibited tumor progression in
      vitro and in vivo. Mechanistically, a target microRNA of circ-BPTF was confirmed
      to be miR-31-5p, and miR-31-5p mimics partially reversed the effect of circ-BPTF.
      Furthermore, RAB27A was predicted and shown to be a target of miR-31-5p, and circ
      BPTF attenuated the anti-oncogenic effect of miR-31-5p and consequently enhanced
      RAB27A expression. In summary, our findings reveal that circ-BPTF promotes BCa
      progression through the miR-31-5p/RAB27A axis, suggesting that circ-BPTF may be a
      potential target for BCa treatment.

PMID- 30103210
TI  - Neural stem cell spacing questions their self-renewal.

PMID- 30103212
TI  - Correction of aging phenotype in the liver.

PMID- 30103211
TI  - Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV
      related hepatocellular carcinoma.
AB  - Anillin (ANLN) is an actin-binding protein essential for assembly of cleavage
      furrow during cytokinesis. Although reportedly overexpressed in various human
      cancers, its role in hepatocellular carcinoma (HCC) is unclear. To address this
      issue, we confirmed that in 436 liver samples obtained from surgically removed
      HCC tissues, higher ANLN expression was detected in tumor tissues than in
      adjacent non-tumor tissues of HCC as measured by immunohistochemistry,
      quantitative real-time PCR and western blotting. Correlation and Kaplan-Meier
      analysis revealed that patients with higher ANLN expression were associated with
      worse clinical outcomes and a shorter survival time, respectively. Moreover, ANLN
      inhibition resulted in growth restraint, reduced colony formation, and a lower
      sphere number in suspension culture. Mechanistically, ANLN deficiency induced an
      increasing number of multinucleated cells along with the activation of apoptosis
      signaling and DNA damage checkpoints. Furthermore, HBV infection increased ANLN
      expression by inhibiting the expression of microRNA (miR)-15a and miR-16-1, both
      of which were identified as ANLN upstream repressors by targeting its 3'
      untranslated region. Thus, we conclude that ANLN promotes tumor growth by ways of
      decreased apoptosis and DNA damage. Expression level of ANLN significantly
      influences the survival probability of HCC patients and may represent a promising
      prognostic biomarker.

PMID- 30103213
TI  - Contrast-Enhanced Ultrasound for Early Prediction of Response of Breast Cancer to
      Neoadjuvant Chemotherapy.
AB  - PURPOSE:  To evaluate the time-intensity curve (TIC) parameters on contrast
      enhanced ultrasound (CEUS) for early prediction of the response of breast cancer
      to neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS:  This prospective study
      included 41 patients with breast cancer. CEUS was performed before and after the
      first cycle of NAC. TIC parameters were analyzed for different regions of
      interest (ROIs). ROI 1 targeted the hotspot area of greatest enhancement, ROI 2
      delineated the area of hyperenhancement, ROI 3 included the entire tumor on
      grayscale ultrasound, and ROI 4 encircled the normal parenchyma. The TIC
      perfusion values for ROI 1, 2, and 3 were divided by the ROI 4 value. RESULTS: 
      11 (26.8 %) of the 41 patients showed a good response (Miller-Payne score 4 or 5)
      and 30 (73.2 %) showed a minor response (Miller-Payne score 1, 2, or 3). There
      were significant differences in the wash-out area under the curve, the wash-in
      and wash-out areas under the curve on ROI 1/4 after the first cycle of NAC, pre
      NAC mean transit time local (mTTl) on ROI 2/4, and pre-NAC mTTl on ROI 3/4
      between good and minor responders (area under the receiver-operating
      characteristic curve > 0.70, p < 0.05). CONCLUSION:  Some TIC parameters obtained
      by CEUS may allow prediction of the response of breast cancer to NAC at a very
      early time point.

PMID- 30103214
TI  - [ICD-11 posttraumatic stress disorder (PTSD) in male prisoners].
AB  - THEORETICAL BACKGROUND: The eleventh version of the ICD, expected to be published
      in 2018, leads to changed criteria for post-traumatic stress disorder (PTSD)
      according to the online beta version. Such changes are likely to affect
      previously known features of PTSD, including the prevalence rate. Little is known
      about the prevalence of ICD-11 PTSD in imprisoned men. The present study examined
      this issue in this high-risk group for trauma disorders, as male prisoners are
      known to be more often affected by traumatic events compared to the general
      population. METHOD: In n = 49 men imprisoned in Switzerland, cross-sectional and
      standardized self-assessment procedures (ACE, Cidi list, IES-R) were used to
      record traumatic events and possible trauma symptoms. The frequency of ICD-11
      PTSD was calculated using the diagnostic heuristic of Hyland et al. (2017), on
      the basis of which ICD-11 PTSD is estimated by means of the IES-R. RESULTS:
      Overall, 88 % of the detained men examined had been traumatized during childhood
      and / or life span; 78 % reported at least one event on the ACE, on average 1.5,
      with 25 % reporting four or more events. Emotional abuse was reported most
      frequently (51 %). Furthermore, 71 % reported at least one event on the Cidi
      list, on average 1.8, with 45 % reporting serious physical threat. The analysis
      of ICD-11 PTSD was carried out with n = 34 inmates after exclusion of those
      without a traumatic event and those who did not complete the IES-R, and ICD-11
      PTSD was estimated at 26.5 %. CONCLUSION: The study shows that imprisoned men are
      likely to be a high risk group for the development of PTSD even according to the
      new ICD. Considering the high prevalence of traumatic events and the numerous
      negative consequences for mental as well as physical health, specific
      psychotherapeutic programs and a trauma-informed imprisonment are necessary.

PMID- 30103215
TI  - Oleic acid increases uptake and decreases the P-gp-mediated efflux of the
      veterinary anthelmintic Ivermectin.
AB  - The bioavailability of ivermectin is modulated by lipid-based formulations and
      membrane efflux transporters such as Breast Cancer Resistance Protein and P
      glycoprotein (BCRP and P-gp). We have investigated the effect of oleic acid on
      the uptake of ivermectin in vitro using Caco-2 cells and in vivo in the
      intestines of wild-type mice. Complex micelles (M) with oleic acid induced a
      significant increase (e. g. for M3 was 7-fold, p<=0.001) in the uptake of the
      drug in a time-dependent manner with no involvement of cholesterol in the
      mechanism. In vivo results showed a significant increase in the concentration of
      plasma and intestinal mucosa ivermectin (p<=0.01) in mice receiving oleic acid
      based drug formulation. We also examined the expression of the drug efflux
      transporter, BCRP and P-gp in Caco-2 cells and found a significant decrease
      (p<=0.001) in their level in the presence of 5 mM oleic acid. Treatment of mice
      with oleic acid-based formulation showed a significant decrease in the activity
      of P-gp in the intestinal mucosa (p<=0.01). This study highlighted the effect of
      oleic acid in decreasing the expression and the activity of P-gp-mediated
      ivermectin efflux and in limiting the drug absorption by increasing its uptake
      and bioavailability in Caco-2 cells and intestine, respectively.

PMID- 30103216
TI  - Effect of Renal Impairment on the Pharmacokinetics and Pharmacodynamics of
      Tofogliflozin (A SELECTIVE SGLT2 Inhibitor) in Patients with Type 2 Diabetes
      Mellitus.
AB  - PURPOSE: Tofogliflozin is an orally available selective inhibitor of sodium
      glucose co-transporter 2 for treatment of type 2 diabetes mellitus (T2DM). Two
      studies were conducted to evaluate the effect of renal impairment on
      pharmacokinetics and pharmacodynamics of tofogliflozin. METHODS: The studies
      were: 1) single dose study in T2DM patients with normal renal function and mild,
      moderate and severe renal impairment, and 2) multiple dose study for 24 weeks in
      T2DM patients with normal renal function and moderate renal impairment. RESULTS:
      Renal function did not have a clinically relevant effect on the PK of
      tofogliflozin. Urinary glucose excretion up to 24 h after administration of
      tofogliflozin (UGE24h) decreased with decreasing glomerular filtration rate.
      Lowering UGE24h resulted in waning glycemic control but not body weight
      reduction. CONCLUSIONS: Single and multiple administrations of tofogliflozin were
      generally well tolerated in T2DM patients with various renal functions. As far as
      investigated here, these studies indicate no dose adjustment is required for
      patients with renal impairment.

PMID- 30103217
TI  - Alterations in Pharmacokinetics of Orally Administered Carbamazepine in Rats
      Treated with Sodium alginate: Possible Interaction between Therapeutic Drugs and
      Semi-solid Enteral Nutrients.
AB  - OBJECTIVE: The use of enteral nutrients plays an extremely important role in
      accurate nutrition management. Sodium alginate (SA) is frequently used for the
      semi-solidification of enteral nutrients. In the present study, we investigated
      whether the pharmacokinetic profile of orally administered carbamazepine (CBZ) is
      altered by a treatment with SA immediately before and after dosing of the drug.
      Furthermore, the adsorption effects of SA on CBZ were examined using an in vitro
      analysis. METHOD: SA was orally administered to rats just before and immediately
      after CBZ dosing. The CBZ concentration profile following its oral administration
      was analyzed by a non-compartmental method. The adsorption of CBZ onto SA was
      evaluated after centrifugation using an ultrafiltration device. FINDINGS: The
      serum concentration of orally administered CBZ at each sampling point was reduced
      by the treatment with SA, and the extent of the decrease observed in the
      concentration of CBZ was larger when SA was ingested immediately after
      administration of the drug, which was consistent with the alteration observed in
      the value of the area under the curve (AUC). No significant differences were
      noted in the elimination rate at the terminal phase (ke) among the groups. In the
      in vitro assay, CBZ was adsorbed by SA in the solution used to reflect fluid in
      the intestinal tract. CONCLUSIONS: The pharmacological efficacies of CBZ might be
      reduced by SA through the pharmacokinetic interactions, and that the careful
      attention should be paid to the timing of administration of CBZ and semi-solid
      enteral nutrients.

PMID- 30103218
TI  - In vivo Evaluation of Anti-Hyperglycemic, Anti-hyperlipidemic and Anti-Oxidant
      Status of Liver and Kidney of Thymol in STZ-Induced Diabetic Rats.
AB  - AIM: The evaluation of the positive and protective effects thymol as a natural
      compound on the STZ -induced diabetic rats. MATERIALS AND METHODS: In this study,
      seven groups of the streptozotocin induced diabetic and normal rats (overall 42
      males) were tested through various biochemical and histopathological factors such
      as: serum glucose, insulin, creatinine, lipids, lipoproteins, liver function
      related enzymes, and antioxidant status in liver and kidney. RESULTS: The
      obtained results in this work indicated that thymol had a significant anti
      hypoglycemic, anti-hypolipidemic activities on the STZ-induced diabetic rats.
      Further, the assessment different biochemical parameters revealed that the levels
      of creatinine, low-density lipoprotein cholesterol, very low density lipoprotein
      cholesterol, and liver function-related enzymes such as aspartate
      aminotransferase and alanine aminotransferase were decreased in the treated
      diabetes rats under 20 and 40 mg/kg thymol compared to the control diabetes
      group. Considerably, the anti-oxidant enzymes status that were achieved from the
      liver and kidney organs were modulated after treatment with thymol in the
      diabetic rats. CONCLUSION: The results of this research has brough a new aspect
      concerning the proteevtive and positive effects of thymol on the diabetic
      complications in the animal model.

PMID- 30103219
TI  - Clinical Outcomes of Closing- and Opening-Wedge High Tibial Osteotomy for
      Treatment of Anteromedial Unicompartmental Knee Osteoarthritis.
AB  - This article compares the long-term outcomes of closing-wedge osteotomy (CWO) and
      opening-wedge osteotomy (OWO) in the treatment of unicompartmental medial
      osteoarthritis with varus deformity. This study included 79 patients who
      underwent high tibial osteotomy (HTO) between 2002 and 2008. Pre- and
      postoperative radiography and computed tomography were used to evaluate the
      posterior tibial slope, the patellar height, the tibiofemoral angle, and the
      lateral and medial tibiofemoral joint space. Pre- and postoperative severity of
      arthritis was assessed with the Kellgren-Lawrence grading system. Pre- and
      postoperative American Knee Society (AKS) score and Lysholm Knee Score (LKS) were
      determined to evaluate functional outcomes. The duration of follow-up was 86.1 +/
      6.2 months. Postoperatively, at the most recent follow-up, there was a slight
      increase in the size of the medial tibiofemoral joint space after CWO and OWO,
      which reflected a decrease in stress on the medial compartment and manifested as
      a significant improvement in the AKS knee and function scores and the LKS. OWO
      increased the posterior tibial slope as compared with the preoperative value,
      while CWO reduced the posterior tibial slope. CWO and OWO for HTO resulted in
      similar functional outcomes. OWO was associated with patella infera and more
      severe patellofemoral arthritis, while CWO was associated with a greater severity
      of lateral tibiofemoral arthritis.

PMID- 30103220
TI  - Cost Analysis of Azithromycin versus Erythromycin in Pregnancies Complicated by
      Preterm Premature Rupture of Membranes.
AB  - OBJECTIVE:  To quantify the potential cost savings if azithromycin is substituted
      for erythromycin in women with preterm premature rupture of membranes (PPROM).
      STUDY DESIGN:  Secondary analysis of a multicentered study investigating
      magnesium sulfate for the prevention of cerebral palsy in premature infants. All
      patients with PPROM who received antibiotics for prophylaxis were included in the
      analysis. The number of expected doses each patient would have received was
      calculated for erythromycin, multidose azithromycin, and single-dose azithromycin
      regimens accounting for latency from PPROM to delivery. The wholesale acquisition
      cost was used to calculate the expected cost of each regimen. RESULTS:  There
      were 981 PPROM patients who received a penicillin class antibiotic and
      erythromycin. Patients would have received 7,528 intravenous doses and 10,194
      oral doses of erythromycin at a combined cost of $357,169. In comparison,
      patients would have received 6,422 and 3,942 doses at a cost of $15,669 and
      $9,574 for the multidose and single-dose azithromycin regimens respectively,
      which represents a more than 95% cost reduction for either regimen compared with
      erythromycin. CONCLUSION:  The use of azithromycin substituted for erythromycin
      in the standard antibiotic regimen of women with PPROM represents a potential for
      substantial cost reduction.

PMID- 30103221
TI  - [Liver disease in systemic Lupus erythematodes - results of an explorative
      observational study].
AB  - INTRODUCTION:  Systemic lupus erythematodes (SLE) represents an autoimmune
      disease with a highly variable clinical course affecting numerous organs. Hepatic
      manifestation seems to be rare. It is not clear whether hepatic disease in SLE is
      of any prognostic importance or whether it correlates with disease activity.
      METHODS:  Our patient cohort included 172 patients with proven SLE, all treated
      at Bogenhausen Hospital between 01.2009 and 12.2015. Retrospectively, all
      admissions as inpatients and outpatients were analyzed (n = 671; mean 3.9 per
      patient). Liver damage was diagnosed by evaluation of laboratory parameters on
      the basis of pathological liver enzymes and by imaging methods. Disease activity
      of SLE was calculated by using European Consensus Lupus Activity Measurement
      (ECLAM-)Score. Additionally, parameters of SLE including disease duration, organ
      damage and immune suppressive medication and their possible association with
      hepatopathy were analyzed. RESULTS:  Elevated liver parameters (ASAT, ALAT, GGT,
      AP) indicating liver damage were detectable in 109 patients (63.4 % of total
      population) demonstrating significant association with disease activity (on the
      basis of ECLAM-score, p < 0.001), duration of treatment, frequency of admissions
      (p < 0.01, respectively), number of used immunosuppressive agents (p < 0.018),
      increased blood sedimentation rate (p < 0.001) and reduction of serum complement
      (p < 0.03). Abnormal ultrasound findings of the liver (e. g., non-alcoholic fatty
      liver disease) were diagnosed in 19.8 %. DISCUSSION:  Elevated liver parameters
      occur frequently in patients with SLE, especially in context with increased
      disease activity (on the basis of ECLAM-Score or intensified immunosuppressive
      therapy) and prolonged course of the disease. Liver enzymes should be obtained
      regularly in patients with SLE and, if necessary, further diagnostic steps should
      be initiated. Further prospective studies might clarify whether abnormal liver
      parameters must be included in activity indices to judge disease activity in SLE.

PMID- 30103222
TI  - [Ustekinumab - Current position].
AB  - The present review by the IBD-Dach group provides a comprehensive summary of the
      mode of action, clinical development, approval, efficacy and safety aspects of
      the novel anti-p40 antibody Ustekinumab. The review provides current data,
      including the large clinical trials as well as smaller case series and work
      outside the field of inflammatory bowel diseases for shedding more light into
      special situations. Together, the data indicate that Ustekinumab shows clinical
      efficacy as well as a good safety profile for the treatment of Crohn's disease.

PMID- 30103223
TI  - ?

PMID- 30103224
TI  - [Wolfgang Schepp MD - Introduction of the conference chairman 2018 of the German
      Society of Gastroenterology, Digestive and Metabolic Diseases].

PMID- 30103225
TI  - ?

PMID- 30103226
TI  - Endoscopic retrograde appendicitis techniques for the treatment of patients with
      acute appendicitis.
AB  - OBJECTIVE: The purpose of this study was to demonstrate the feasibility of
      endoscopic retrograde appendicitis therapy (ERAT) in treating patients with acute
      appendicitis. MATERIALS AND METHODS: Between January 2014 and December 2014, 22
      patients with acute appendicitis underwent ERAT. Patient demographics,
      colonoscopy findings, endoscopic retrograde appendiceal radiography (ERAR)
      findings, and treatment outcomes of the ERAT and adverse events associated with
      ERAT were analyzed. RESULTS: In this study, 22 patients with acute appendicitis
      underwent ERAT. The median age of the patients was 39.5 years. Colonoscopy
      findings included mucosal hyperemia and swelling of the appendiceal orifice
      and/or its surrounding mucosa (86.4 %, 19/22) and pus at the appendiceal orifice
      (40.9 %, 9/22). ERAR findings included irregular contour (76.2 %, 16/21),
      appendiceal lumen dilation (28.6 %, 6/21), appendiceal lumen stenosis (42.9 %,
      9/21), and filling defect of the appendiceal lumen (23.8 %, 5/21). Deep
      intubation was successfully performed in 21 of the 22 patients (95.5 %). Sixteen
      patients underwent endoscopic appendiceal stent placement after endoscopic
      appendiceal irrigation (EAI) due to lumen stenosis of the appendiceal, excessive
      pus, or appendiceal fecalith, and the remaining 6 patients only underwent EAI.
      Among the 22 patients who underwent ERAT, their abdominal pain was noticeably
      relieved following the procedure. The main adverse events associated with ERAT
      were spontaneous discharge of the stent, recurrent abdominal pain, and recurrent
      appendicitis. During the follow-up (median 33 months), 2 patients underwent
      laparoscopic appendectomy. CONCLUSIONS: ERAT provide a new alternative
      therapeutic method for patients with acute appendicitis, particularly for certain
      patients who are unwilling to undergo an appendectomy.

PMID- 30103227
TI  - Colorectal MALT lymphoma: a rare clinical entity.
AB  - BACKGROUND: Data on colorectal lymphoma in general and on MALT (mucosa-associated
      lymphoid tissue) lymphoma, in particular are, very rare. There are no existing
      recommendations from current guidelines for how to manage these patients. We here
      report our experience from a clinical series. AIM: The aim of this study is to
      present clinical features and the endoscopic appearance of colorectal MALT
      lymphoma and therapeutic approaches. METHODS: Seven patients (5 male and 2
      female, aged 47 - 75 years) were diagnosed to have colorectal MALT lymphoma. All
      patients underwent a full staging work-up. A concurrent gastric MALT lymphoma was
      present in 2 patients. Follow-up was 37 (0 - 53) months. RESULTS: Colorectal MALT
      lymphoma was diagnosed by screening or staging colonoscopy in 3 and 1 patient,
      revealing no clinical symptoms, respectively. Two patients complained about
      fatigue, obstipation, and a change in bowel habits. The endoscopic appearance of
      the MALT lymphoma comprised obstructive tumors (n = 2), polyps (n = 3), a flat
      lesion (n = 1), and vascular angiectasia (n = 1). In 6 cases, colorectal MALT
      lymphoma presented as a solitary lesion. Following endoscopic polypectomy,
      surgical resection, Helicobacter pylori eradication therapy, or systemic immune
      chemotherapy, complete remission of lymphoma was achieved in 5 cases, while the
      outcome is unknown or cannot yet be estimated in 2 cases. CONCLUSION: A treatment
      and management approach based on the clinical and local presentation of the
      lymphoma and its involvement is proposed.

PMID- 30103228
TI  - [Updated S3-Guideline for Prophylaxis, Diagnosis and Treatment of Gallstones.
      German Society for Digestive and Metabolic Diseases (DGVS) and German Society for
      Surgery of the Alimentary Tract (DGAV) - AWMF Registry 021/008].
AB  - This guideline provides evidence-based key recommendations for the prevention,
      diagnosis and therapy of gallstones and upgrades the 2007 version. The guideline
      was developed by an interdisciplinary team of gastroenterologists and surgeons,
      and patient support groups under the auspice of the German Society for
      Gastroenterology and Metabolic Diseases and the German Society for General
      Surgery and Surgery of the Alimentary Tract. The guideline used structural S3
      consensus-based methodology and includes statements on clinical practice, medical
      education, prevention, quality assurance, outcome analysis, and integration of
      outpatient and inpatient care for patients with gallstone diseases.

PMID- 30103229
TI  - The clinical relevance of laryngopharyngeal reflux monitoring is poor.

PMID- 30103230
TI  - ?

PMID- 30103231
TI  - The Effect of Injury Definition and Surveillance Methodology on Measures of
      Injury Occurrence and Burden in Elite Volleyball.
AB  - A time-loss injury definition continues to be the most widely used injury
      definition despite evidence that it fails to accurately capture overuse injuries.
      An overuse injury questionnaire, using an "all complaints" definition has been
      created to address the limitation of a time-loss definition. The main aim of this
      work was to determine the effect that injury definition and registration
      methodology has on the collection of knee injuries among elite level volleyball
      players. To reach this goal, seventy-two volleyball players were prospectively
      followed over 32-weeks. Time-loss injuries were captured using an individual
      injury report form (IIRF). Study participants completed an overuse injury
      questionnaire (mOIQ) via a weekly short message service (SMS). The IIRF captured
      15 time-loss knee injuries in 72 study participants (20%). Based on the mOIQ,
      84.7% of participants reported having a knee problem and 66.7% sustained a
      substantial knee problem. All IIRF knee injuries captured were also registered by
      the mOIQ. Agreement on the specific diagnosis occurred for 66.7% of injuries
      resulting in a moderate Kappa score of 0.51. In conclusion, an overuse injury
      questionnaire provided a greater understanding of the magnitude and burden of
      knee injuries in this population.

PMID- 30103232
TI  - From Global Health Challenges to Community-Based and Individual Psychosocial
      Intervention Strategies.
AB  - Liebe Kolleginnen und Kollegen,wir freuen uns, Sie im Namen beider
      Fachgesellschaften und des Leipziger Kongressteams zur gemeinsamen Jahrestagung
      der Deutschen Gesellschaft fur Medizinische Psychologie (DGMP) und der Deutschen
      Gesellschaft fur Medizinische Soziologie (DGMS) einzuladen, die vom 26. bis 28.
      September 2018 auf dem Campus der Universitat Leipzig stattfindet (www.dgmp-dgms
      2018.de).

PMID- 30103233
TI  - Higher Detection Rates of Biologically Aggressive Breast Cancers in Mammography
      Screening than in the Biennial Interval.
AB  - PURPOSE:  Assessment of age group-dependent detection rates of invasive breast
      cancers among participants in mammography screening including the interval,
      classified into immunohistochemical subtypes indicating the intrinsic tumor
      aggressiveness. MATERIALS UND METHODS:  The target population comprises women
      aged 50 - 69 years. All invasive breast cancers diagnosed in one screening (sc)
      unit during the implementation phase 1/2006 - 12/2010 or identified by the cancer
      registry during the biennial interval (iv) were categorized based on hormonal
      receptor status (HR) and Her2-expression (Her2) into the following subtypes: a)
      HR+ Her2-, b) HR+ Her2 +, c) HR- Her2 + or d) HR- Her2- (triple-negative); Her2 +
      and triple-negative types were defined as aggressive. The calculated detection
      rates (DR, 0/00) were based on 53 375 sc-examinations and for the interval on 52
      887 sc-negative examinations. RESULTS:  The DRs of all subtypes were higher in
      screening versus the interval: (a) 4.95 0/00 (n = 264) vs. 1.00 0/00 (n = 53); b)
      0.92 0/00 (n = 49) vs. 0.25 0/00 (n = 13); c) 0.36 0/00 (n = 19) vs. 0.06 0/00 (n
      = 3); d) 0.39 0/00 (n = 21) vs. 0.19 0/00 (n = 10). 77.4 0/00 (89/115) of all
      aggressive breast cancers including the following 2-year interval were diagnosed
      by screening. The sum of the DR of aggressive cancers was 1.67 0/00 in screening
      and 0.49 0/00 in the interval; the corresponding DRs for women aged 60 - 69 years
      [sc: 2.24 0/00 (51/22 814), iv: 0.58 0/00 (13/22 536)] were higher than among
      women aged 50 - 59 years [sc: 1.24 0/00 (38/30 561), iv: 0.43 0/00 (13/30 351)].
      CONCLUSION:  Screening has the potential for earlier diagnosis of aggressive
      tumor types as its detection rate is about three-fold higher compared to the
      interval. Within the target group, participants aged 60 - 69 years are at risk
      based on absolute numbers. They show a nearly two-fold higher detection rate of
      Her2-positive or triple-negative tumors compared to the age group 50 - 59 years.
      KEY POINTS:   . Her2-positive and triple-negative detection rates are higher in
      screening than in the interval.. . 77 % of aggressive subtypes are diagnosed by
      screening, 23 % during the 2-year interval.. . The detection rate is highest
      among women aged 60 - 69 years in screening.. CITATION FORMAT: . Prange A, Bokhof
      B, Polzer P et al. Higher Detection Rates of Biologically Aggressive Breast
      Cancers in Mammography Screening than in the Biennial Interval. Fortschr
      Rontgenstr 2018; DOI: 10.1055/a-0657-3970.

PMID- 30103234
TI  - New Approach for B-Mode Ultrasound (US) Evaluation of the Plantar Aponeurosis
      (PA) Thickness in Healthy Subjects.
AB  - PURPOSE:  To compare ultrasound (US) measurements in the sagittal and axial plane
      of the plantar aponeurosis (PA) in healthy subjects. MATERIALS AND METHODS:  PA
      thickness was measured in 40 healthy subjects (mean age: 34 years) by two
      radiologists using US in sagittal, axial medial and axial lateral planes.
      Subjects were classified according to gender (female and male) and age (18 - 35
      versus 50 - 75 years). All measurements were compared and the interobserver
      agreement was calculated. RESULTS:  The PA was medially significantly thicker
      than laterally (mean +/- std 3.1 +/- 0.7 mm versus 2.5 +/- 0.5 mm respectively,
      P< 0.001). A significant difference was found between males and females (3.3 +/-
      0.7 mm versus 2.9 +/- 0.6 mm medially and 2.7 +/- 0.6 mm versus 2.3 +/- 0.4 mm
      laterally, p < 0.05) and between the older and younger age groups (3.8 +/- 0.6 mm
      versus 2.8 +/- 0.4 mm medially and 3.1 +/- 0.4 mm versus 2.3 +/- 0.4 mm
      laterally, p < 0.001). Good interobserver agreement was detected (0.74).
      CONCLUSION:  Measurement of central and lateral fascicles of the plantar
      aponeurosis in both planes (sagittal and axial) is recommended in the daily
      routine. KEY POINTS:   . US examination of the central and lateral fascicles of
      the PA was feasible.. . PA thickness measurements showed significant differences
      based on age and gender.. . There was good interobserver correlation between both
      examiners despite the major difference in experience.. . Scanning of two planes
      for the PA is recommended in the daily routine.. . PA thickness measurement by US
      is a fast and reliable method for junior radiologists.. CITATION FORMAT: . Abd
      Ellah MM, Kremser C, Strobl S et al. New Approach for B-Mode Ultrasound (US)
      Evaluation of the Plantar Aponeurosis (PA) Thickness in Healthy Subjects.
      Fortschr Rontgenstr 2018; DOI: 10.1055/a-0657-3905.

PMID- 30103235
TI  - The Role of Brain Connectome Imaging in the Estimation of Depressive Relapse
      Risk.
AB  - BACKGROUND:  About two-thirds of all patients with major depressive disorder
      (MDD) suffer from depressive relapse, the mechanisms of which are still poorly
      understood. In recent years, analyses of the brain's connectome have increasingly
      been employed to identify potential biomarkers of depressive relapse. The term
      "connectome" refers to the map of all structural or functional connections in the
      brain. It can be investigated by structural or functional magnetic resonance
      imaging followed by graph theory-based analysis to characterize network topology
      on the global and regional level. METHODS:  This review is based on a selective
      literature search in PubMed representing the current state of research, as well
      as on an already published study which was awarded the Promotionspreis of the
      Deutsche Rontgengesellschaft. RESULTS AND CONCLUSION:  Numerous studies point to
      altered network topology, e. g., of default-mode network and striatum, as being
      crucial for the pathophysiology of MDD. Our group was able to show that striatal
      centrality (or hubness) is associated with the number of depressive episodes,
      which is one of the best predictors for depressive relapse. These data suggest
      aberrant striatal network topology as a potential biomarker for depressive
      relapse risk. The translation of these promising findings into clinical routine
      diagnostics is promoted by several methodological advantages, while some
      unresolved issues still hinder this process. KEY POINTS:   . About two-thirds of
      all patients with MDD suffer from depressive relapse.. . The mechanisms of
      depressive relapse are still poorly understood.. . Imaging the brain's connectome
      can contribute to better understanding of depressive relapse.. . The term
      "connectome" comprises all structural and functional connections of the brain.. .
      Altered striatal network topology could be associated with depressive relapse
      risk.. CITATION FORMAT: . Brandl F, Meng C, Zimmer C et al. The Role of Brain
      Connectome Imaging in the Estimation of Depressive Relapse Risk. Fortschr
      Rontgenstr 2018; 190: 1036 - 1043.

PMID- 30103236
TI  - Structured Reporting in Clinical Routine.
AB  - BACKGROUND:  The radiology report is the key component in the communication
      between radiologists and referring clinicians. Traditionally, reports are written
      as free text. Several studies have shown that structured reporting using
      dedicated report templates has a number of advantages compared to conventional
      reports. Therefore, many radiological societies have recommended the
      implementation of structured reporting in clinical routine. METHOD:  In the
      meantime, collections of freely available templates have been presented and
      software solutions for structured reporting have been made commercially
      available. These allow for quality improvements in the written radiology report
      as they ensure that all relevant clinical information is included. Most vendors
      mainly supply proprietary report templates or allow users to create templates for
      their own institution. The German Radiological Society (DRG) has the goal of
      developing consensus-based, quality-assured report templates and providing them
      under a free license. RESULTS:  The DRG has developed its first consensus-based
      report templates and provides them at www.befundung.drg.de. Further report
      templates will be developed in close cooperation with the respective committees
      of the DRG and referring clinicians. CONCLUSION:  Structured reporting allows for
      a significant improvement in the quality of written radiology reports. The use of
      report templates requires personal and technical changes to the reporting process
      itself. Radiology should face these challenges in its leading role in the
      application of modern IT-based solutions. Vendors are now encouraged to provide
      practical solutions. KEY POINTS:   . Structured reports have numerous advantages
      over conventional narrative reports.. . The German Radiological Society is
      developing consensus-based and quality assured report templates.. . Report
      templates are provided at www.befundung.drg.de under a free license.. . Vendors
      are now encouraged to provide solutions for the implementation of structured
      reporting.. CITATION FORMAT: . Pinto dos Santos D, Hempel J, Mildenberger P et
      al. Structured Reporting in Clinical Routine. Fortschr Rontgenstr 2018; DOI:
      10.1055/a-0636-3851.

PMID- 30103237
TI  - 4D-Flow MRI: Technique and Applications.
AB  - BACKGROUND:  Blood flow through the cavities of the heart and great vessels is
      pulsatile and is subject to time and multidirectional variations. To date, the
      recording of blood flow in multiple directions and phases has been limited. 4D
      flow MRI offers advantages for the recording, visualization and analysis of blood
      flow. METHOD:  The status quo of the method was summarized through analysis with
      the PubMed database using the keywords "4D-flow MRI, phase-contrast magnetic
      resonance imaging, MR flow imaging/visualization, MR flow quantification, 3 D
      cine (time-resolved) phase-contrast CMR, three-directional velocity-encoding
      MRI". RESULTS/CONCLUSION:  This review summarizes the current status of the
      technical development of 4D-flow MRI, discusses its advantages and disadvantages
      and describes clinical applications. Finally, the most important principles and
      parameters are explained to give the reader relevant information about clinical
      indications, postprocessing methods and limitations of the method. KEY POINTS:  
      . 4D-Fluss-MRT. . 3-dimensionale zeitaufgeloste Phasenkontrast-MRT. .
      Flussanalyse-MRT (Wall-Shear-Stress/Druckgradienten-Messung/Vortex
      Fluss/turbulente kinetische Energie/Flussgeschwindigkeit/Flussrate). CITATION
      FORMAT: . Strater A, Huber A, Rudolph J et al. 4D-Flow MRI: Technique and
      Applications. Fortschr Rontgenstr 2018; 190: 1025 - 1035.

PMID- 30103238
TI  - Proximity to the Diaphragm Predicts the Presence of Rhabdomyomatous Dysplasia in
      Congenital Pulmonary Airway Malformations.
AB  - INTRODUCTION:  Rhabdomyomatous dysplasia (RD) is a pathologic finding in CPAMs
      that was incorrectly attributed to their malignant potential. The increasing
      recognition of extrathoracic (intradiaphragmatic and intraabdominal) congenital
      pulmonary airway malformations (CPAMs) offers a clue to the origin of RD. We
      hypothesize that the presence of RD is related to the CPAM's anatomic location.
      MATERIALS AND METHODS:  Retrospective review was performed of all children who
      underwent resection of a CPAM during a 10-year period. The age at the time of
      operation, location of the CPAM, and pathologic findings were collected.
      Peridiaphragmatic location was defined as within the inferior pulmonary ligament,
      deep to the diaphragmatic portion of the parietal pleura ("intradiaphragmatic")
      or adjacent to the abdominal side of the diaphragm. Statistical analysis was
      performed using Fisher's exact test for 2 * 2 tables. RESULTS:  Twenty-six
      patients with CPAM were identified. Preoperative imaging was performed by
      computed tomography (CT) scan (16/26), ultrasound (5/26), magnetic resonance
      imaging (MRI) (1/26), and chest radiograph (4/26). The median age at resection
      was 15 months. Of these, 16 were pure cystic adenomatoid malformations, 4 were
      extralobar sequestrations, 4 were intralobar sequestrations, and 2 were
      bronchogenic cysts. Nine lesions were peridiaphragmatic with four being
      intradiaphragmatic (44%). Eight of the nine resected peridiaphragmatic lesions
      contained histologic evidence of rhabdomyomatous changes (89%, confidence
      interval [CI] 52-99%). None of the other lesions contained RD (CI 0-19%, p <
      0.001). CONCLUSION:  RD was seen exclusively, and in virtually all
      peridiaphragmatic CPAMs. While the exact significance of RD remains unclear, it
      may represent incorporation of striated muscle tissue associated with the
      developing diaphragm.

PMID- 30103239
TI  - Nonsurgical Treatment of Chest Wall Deformities: Contradiction or Complement?
AB  - For decades, open surgical repair was the only available method to treat
      congenital and acquired chest wall deformities (CWDs). In 1998, D. Nuss described
      a minimally invasive procedure for surgical repair of pectus excavatum (PE), and
      a few years later H. Abramson reported on his experience with the "reversed Nuss
      technique" for surgical repair of pectus carinatum (PC). Both procedures are
      performed with increasing frequency worldwide.However, nonsurgical measures such
      as vacuum bell (VB) therapy for conservative treatment of PE and more
      differentiated bracing systems for conservative treatment of PC were established
      15 to 20 years ago. Nowadays, information on new therapeutic modalities
      circulates not only among surgeons and pediatricians, but also rapidly among
      patients. In particular, patients who refused operative treatment by previously
      available procedures now appear at the outpatient clinic and request to be
      considered for the new methods.Analyzing the increasing number of studies
      reporting on conservative treatment of CWDs as well as our own group of patients
      who visited a busy outpatient clinic in a small country within the last 15 to 20
      years, we have to realize that the majority of patients asked for nonsurgical
      treatment of their CWD. Based on these experiences and results, we have to
      realize that nonsurgical treatment of CWD is no contradiction but a helpful
      complement to treat congenital and acquired CWDs and may be applied for the
      majority of patients suffering from a CWD.

PMID- 30103240
TI  - Cardiopulmonary Function in Thoracic Wall Deformities: What Do We Really Know?
AB  - Patients with pectus excavatum (PE) frequently present with complaints of
      exercise intolerance and cardiopulmonary symptoms. There continues to be
      controversy regarding the physiologic benefits of repair. The aim of this review
      is to summarize and discuss recent data regarding the cardiopulmonary effects of
      PE deformity and the evidence for improvement obtained after surgical repair
      including (1) a greater efficiency of breathing (chest wall mechanics), (2)
      improvement in pulmonary restrictive deficits, (3) an increase in cardiac chamber
      size and output, with improved cardiac strain and strain rate, and (4)
      improvement in exercise capacity.

PMID- 30103241
TI  - Genotype-Phenotype Association and Impact on Outcomes following Guided De
      Escalation of Anti-Platelet Treatment in Acute Coronary Syndrome Patients: The
      TROPICAL-ACS Genotyping Substudy.
AB  - BACKGROUND:  Phenotype-guided de-escalation (PGDE) of P2Y12-inhibitor treatment
      with an early switch from prasugrel to clopidogrel was identified as an effective
      alternative treatment strategy in acute coronary syndrome (ACS) patients
      undergoing percutaneous coronary intervention (PCI). The Testing Responsiveness
      to Platelet Inhibition on Chronic Antiplatelet Treatment for Acute Coronary
      Syndromes (TROPICAL-ACS) Genotyping Substudy aimed to investigate whether CYP2C19
      genotypes correlate with on-treatment platelet reactivity (PR) in ACS patients
      treated with clopidogrel or prasugrel and thus might be useful for guidance of
      early de-escalation of anti-platelet treatment. METHODS AND RESULTS:  A total of
      603 ACS consecutive patients were enrolled in four centres (23.1% of the overall
      TROPICAL-ACS population). Rapid genotyping (Spartan RX) for CYP2C19*2, *3 and *17
      alleles was performed. Associations between PR and the primary and secondary
      endpoints of the TROPICAL-ACS trial and CYP2C19*2 and CYP2C19*17 carrier status
      were evaluated.For the PGDE group, the on-clopidogrel PR significantly differed
      across CYP2C19*2 (p < 0.001) and CYP2C19*17 genotypes (p = 0.05). Control group
      patients were not related (p = 0.90, p = 0.74) to on-prasugrel PR. For high PR
      versus non-high PR patients within the PGDE group, significant differences were
      observed for the rate of CYP2C19*2 allele carriers (43% vs. 28%, p = 0.007).
      CONCLUSION:  CYP2C19*2 and CYP2C19*17 carrier status correlates with PR in ACS
      patients treated with clopidogrel and thus might be useful for pre-selecting
      patients who will and who may not be suitable for PGDE of anti-platelet
      treatment. Regarding phenotype-guided treatment, we did not observe added benefit
      of genotyping to predict ischaemic and bleeding risk in patients who underwent a
      PGDE approach. CLINICAL TRIAL REGISTRATION:  URL: https//www.clinicaltrials.gov.
      Unique Identifier: NCT: 01959451.

PMID- 30103242
TI  - Genome-Wide Association Study Links Receptor Tyrosine Kinase Inhibitor Sprouty 2
      to Thrombocytopenia after Coronary Artery Bypass Surgery.
AB  - INTRODUCTION:  Thrombocytopenia after cardiac surgery independently predicts
      stroke, acute kidney injury and death. To understand the underlying risks and
      mechanisms, we analysed genetic variations associated with thrombocytopenia in
      patients undergoing coronary artery bypass grafting (CABG) surgery. MATERIALS AND
      METHODS:  Study subjects underwent isolated on-pump CABG surgery at Duke
      University Medical Center. Post-operative thrombocytopenia was defined as
      platelet count < 100 * 109/L. Using a logistic regression model adjusted for
      clinical risk factors, we performed a genome-wide association study in a
      discovery cohort (n = 860) and validated significant findings in a replication
      cohort (n = 296). Protein expression was assessed in isolated platelets by
      immunoblot. RESULTS:  A total of 63 single-nucleotide polymorphisms met a priori
      discovery thresholds for replication, but only 1 (rs9574547) in the intergenic
      region upstream of sprouty 2 (SPRY2) met nominal significance in the replication
      cohort. The minor allele of rs9574547 was associated with a lower risk for
      thrombocytopenia (discovery cohort, odds ratio, 0.45, 95% confidence interval,
      0.30-0.67, p = 9.76 * 10-5) with the overall association confirmed by meta
      analysis (meta-p = 7.88 * 10-6). Immunoblotting demonstrated expression of SPRY2
      and its dynamic regulation during platelet activation. Treatment with a
      functional SPRY2 peptide blunted platelet extracellular signal-regulated kinase
      (ERK) phosphorylation after agonist stimulation. CONCLUSION:  We identified the
      association of a genetic polymorphism in the intergenic region of SPRY2 with a
      decreased incidence of thrombocytopenia after CABG surgery. Because SPRY2-an
      endogenous receptor tyrosine kinase inhibitor-is present in platelets and
      modulates essential signalling pathways, these findings support a role for SPRY2
      as a novel modulator of platelet responses after cardiac surgery.

PMID- 30103243
TI  - Risk Score for Prediction of 10-Year Atrial Fibrillation: A Community-Based
      Study.
AB  - PURPOSE:  We used a large real-world data from community settings to develop and
      validate a 10-year risk score for new-onset atrial fibrillation (AF) and
      calculate its net benefit performance. METHODS:  Multivariable Cox proportional
      hazards model was used to estimate effects of risk factors in the derivation
      cohort (n = 96,778) and to derive a risk equation. Measures of calibration and
      discrimination were calculated in the validation cohort (n = 48,404). RESULTS: 
      Cumulative AF incidence rates for both the derivation and validation cohorts were
      5.8% at 10 years. The final models included the following variables: age, sex,
      body mass index, history of treated hypertension, systolic blood pressure >= 160
      mm Hg, chronic lung disease, history of myocardial infarction, history of
      peripheral arterial disease, heart failure and history of an inflammatory
      disease. There was a 27-fold difference (1.0% vs. 27.2%) in AF risk between the
      lowest (-1) and the highest (9) sum score. The c-statistic was 0.743 (95%
      confidence interval [CI], 0.737-0.749) for the derivation cohort and 0.749 (95%
      CI, 0.741-0.759) in the validation cohort. The risk equation was well calibrated,
      with predicted risks closely matching observed risks. Decision curve analysis
      displayed consistent positive net benefit of using the AF risk score for decision
      thresholds between 1 and 25% 10-year AF risk. CONCLUSION:  We provide a simple
      score for the prediction of 10-year risk for AF. The score can be used to select
      patients at highest risk for treatments of modifiable risk factors, monitoring
      for sub-clinical AF detection or for clinical trials of primary prevention of AF.

PMID- 30103246
TI  - Nursing Home Residents with Venous Thrombosis: A Vulnerable, Fragile and
      Disenfranchised Population.

PMID- 30103244
TI  - Benefit of Risk Score-Guided Prophylaxis in Pregnant Women at Risk of Thrombotic
      Events: A Controlled Before-and-After Implementation Study.
AB  - BACKGROUND:  Management of pregnant women at risk of venous thromboembolism (VTE)
      and placental vascular complications (PVCs) remains complex. Guidelines do not
      definitively specify optimal strategies. OBJECTIVE:  Our objective was to
      evaluate the impact of employing risk score-driven prophylaxis strategies on VTE
      and PVC rates in at-risk pregnant women. MATERIALS AND METHODS:  This study,
      conducted in 21 French maternity units, compared VTE and PVC rates before and
      after implementation of a risk scoring system to determine prophylactic
      strategies. RESULTS:  A total of 2,085 pregnant women at risk of VTE or PVC were
      enrolled. Vascular events occurred in 190 (19.2%) patients before and 140 (13.0%)
      after implementation of risk score-driven prophylaxis (relative risk [RR] = 0.68
      [0.55; 0.83]). The incidence of deep vein thrombosis during pregnancy was reduced
      (RR = 0.30 [0.14; 0.67]). PVC comprised mainly pre-eclampsia, occurring in 79
      patients before and 42 patients after risk score implementation (RR = 0.52 [0.36;
      0.75]). Post-partum haemorrhage occurred in 32 patients (3.2%) before and 48
      patients (4.5%) after risk score implementation (RR = 1.38 [0.89; 2.13], p =
      0.15). CONCLUSION:  Use of a simple risk scoring system, developed by experts in
      VTE and PVC research to guide prophylaxis, reduced the risk of thrombotic events
      during pregnancy without any significant increase in bleeding risk.

PMID- 30103247
TI  - Reticulated Platelets: Changing Focus from Basics to Outcomes.
AB  - Platelets play an essential role in the pathophysiology of atherothrombosis.
      Reticulated platelets (RPs) are the youngest platelet population in the
      circulation; their presence is an indicator of platelet turnover. Circulating
      levels of RPs are increased in patients with coronary artery disease and stroke.
      Preliminary indications are that the proportion of circulating RP is associated
      with the likelihood of ischaemic events such as acute coronary syndrome and
      stroke. Plausible mechanisms include: (1) increased participation of these
      platelets in thrombosis due to messenger ribonucleic acid that may be translated
      to active proteins, (2) lack of exposure to anti-platelet drugs since they are
      newly released from the bone marrow or (3) their presence is a non-specific
      marker of inflammation. In this state-of-the-art review, we discuss the
      implication of RP in coronary artery disease and in hypo-responsiveness to the
      most commonly used anti-platelet drugs.

PMID- 30103245
TI  - Endothelial Cells Harbouring the JAK2V617F Mutation Display Pro-Adherent and Pro
      Thrombotic Features.
AB  - Thromboembolic events are the main cause of mortality in BCR-ABL1-negative
      myeloproliferative neoplasms (MPNs) but their underlying mechanisms are largely
      unrecognized. The Janus kinase 2 (JAK2)V617F mutation is the most frequent
      genetic alteration leading to MPN. Usually found in haematopoietic progenitors
      and stem cells, this mutation has also been described in endothelial cells (ECs)
      of MPN patients. In this study, we have questioned the impact of the JAK2V617F
      mutation on EC phenotype and functions. We developed an induced pluripotent stem
      cells strategy to compare JAK2 mutant and wild-type ECs. Transcriptomic assays
      showed that several genes and pathways involved in inflammation, cell adhesion
      and thrombotic events were over-represented in JAK2V617F ECs and expression
      levels of von Willebrand factor and P-selectin (CD62P) proteins were increased.
      Finally, we found that leucocytes from MPN patients adhere more tightly to
      JAK2V617F ECs. Our results show that JAK2V617F ECs have a pro-inflammatory and
      pro-thrombotic phenotype and were functionally pro-adherent.

PMID- 30103248
TI  - Dual Pathway Inhibition with Low-Dose Direct Factor Xa Inhibition after Acute
      Coronary Syndromes-Why Is It Not Used in Clinical Practice?
AB  - The optimal anti-thrombotic therapy for secondary prevention after an acute
      coronary syndrome is still a matter of debate. While current guidelines recommend
      dual anti-platelet therapy with aspirin and a P2Y12 inhibitor over 12 months
      especially in patients with stent implantation, the value of prolonged
      anticoagulation is still controversial. In the ATLAS-TIMI 52 trial, a low-dose
      direct factor Xa inhibition with rivaroxaban compared with placebo reduced the
      combined primary endpoint of cardiovascular mortality, myocardial infraction and
      stroke with an increase in major bleeding complications. This article discusses
      the value and problems of adding low-dose rivaroxaban to anti-platelet therapy as
      secondary prevention measure after an acute myocardial infarction. It will
      describe the pros and cons of intensified anti-platelet therapy versus dual
      pathway inhibition and give recommendations for different patient groups in
      clinical practice.

PMID- 30103249
TI  - Thromboembolism Incidence and Risk Factors in Children with Cancer: A Population
      Based Cohort Study.
AB  - There is conflicting information about the epidemiology of thromboembolism (TE)
      in paediatric oncology. Objectives were to describe the incidence and risk
      factors of TE in children with cancer. We included all children with cancer less
      than 15 years of age diagnosed from 2001 to 2016, treated at one of the 12
      Canadian paediatric centres outside of Ontario and entered into the Cancer in
      Young People-Canada database. Potential risk factors for TE were evaluated using
      Cox proportional hazards regression stratified by haematological malignancies
      versus solid tumours. Factors associated with vascular access- and non-vascular
      access-related TE were compared using chi-square or Fisher's exact tests. Of the
      7,471 children included, 283 experienced TE requiring medical intervention;
      cumulative incidence of TE at 5 years was 3.8 +/- 0.2% and 0.36% +/- 0.07% for
      life-threatening or fatal TE. For haematological malignancies, the following
      factors were associated with TE in multivariable regression: age < 1 year, 5 to
      9.99 years and 10 to 14.99 years (relative to age 1-4.99 years), haematopoietic
      stem cell transplant (hazard ratio [HR] = 1.49, 95% confidence interval [CI],
      1.00-2.32), anthracyclines (HR = 2.21, 95% CI, 1.12-4.37) and asparaginase (HR =
      1.68, 95% CI, 1.15-2.44). For solid tumours, obesity (HR = 1.92, 95% CI, 1.01
      3.68), surgery (HR = 2.70, 95% CI, 1.44-5.08), radiation (HR = 47.51, 95% CI,
      24.01-94.01), anthracyclines (HR = 2.74, 95% CI, 1.29-5.82) and platinum agents
      (HR = 2.26, 95% CI, 1.19-4.28) were associated with TE. Life-threatening and
      fatal TEs were more common among non-vascular access TEs (14.5% vs. 3.3% p =
      0.001). In a population-based cohort, 4% of children with cancer developed a
      clinically significant TE. Accurate risk stratification tools are needed specific
      to malignancy type.

PMID- 30103251
TI  - JAK2 and Endothelial Function: New Options for Anti-Thrombotic Therapies.

PMID- 30103250
TI  - All-Cause Mortality Risk with Direct Oral Anticoagulants and Warfarin in the
      Primary Treatment of Venous Thromboembolism.
AB  - Oral anticoagulants used for the primary treatment of venous thromboembolism
      (VTE) include warfarin and the more recently introduced direct oral
      anticoagulants (DOACs), including rivaroxaban, apixaban, dabigatran and edoxaban.
      Information on the comparative safety of these medications in routine clinical
      practice is lacking. We identified patients with diagnoses for VTE and
      prescriptions for oral anticoagulants using claims data from a large U.S.
      insurance database from 2012 to 2017. Marginal structural logistic models were
      used to examine associations between type of oral anticoagulant and risk of all
      cause mortality. Of 62,431 enrolees in this analysis, 51% were female and the
      mean age was 61.9 years. Initial oral anticoagulant prescriptions were for
      warfarin (n = 35,704), rivaroxaban (n = 21,064) and apixaban (n = 5,663). A total
      of 1,791 deaths occurred within 6 months of the initial oral anticoagulant
      prescription. Risk of all-cause mortality was not associated with having a
      prescription for warfarin versus any DOAC or between any head-to-head DOAC
      comparisons. Also, associations generally did not vary when stratified by VTE
      type, sex, age, co-morbidities (including renal disease) or anti-platelet
      medication use. In this observational study, the associations with all-cause
      mortality comparing DOACs versus warfarin agree with results from previous
      clinical trials and observational studies, while the associations for head-to
      head DOAC comparisons provide new information on the comparative safety of DOACs.
      Our findings suggest that other criteria such as patient preference, cost,
      recurrent VTE risk or bleeding risk should be used when determining the choice of
      anticoagulant for the primary treatment of VTE.

PMID- 30103252
TI  - Apixaban versus Dalteparin for the Treatment of Acute Venous Thromboembolism in
      Patients with Cancer: The Caravaggio Study.
AB  - International and national guidelines recommend low-molecular-weight heparin for
      the treatment of venous thromboembolism (VTE) in patients with cancer. The aim of
      the Caravaggio study is to assess whether oral apixaban is non-inferior to
      subcutaneous dalteparin for the treatment of acute proximal deep vein thrombosis
      and/or pulmonary embolism in patients with cancer. The study is an investigator
      initiated, multi-national, prospective, randomized, open-label with blind end
      point evaluation (PROBE), non-inferiority clinical trial (NCT03045406).
      Consecutive patients are randomized to receive oral apixaban or subcutaneous
      dalteparin for 6 months. Apixaban is given at a dose of 10 mg twice daily for the
      first 7 days and then 5 mg twice daily; dalteparin is given at a dose of 200
      IU/kg for the first month and then 150 IU/kg once daily. The primary outcome of
      the study is objectively confirmed recurrent VTE as assessed by a central
      independent adjudication committee unaware of study treatment allocation. The
      primary safety outcome is major bleeding defined according to the guidelines of
      the International Society of Thrombosis and Haemostasis. Assuming a 6-month
      incidence of the primary outcome of 7% with dalteparin and an upper limit of the
      two-sided 95% confidence interval of the hazard ratio below the pre-specified
      margin of 2.00, 1,168 patients will be randomized considering an up to 20% loss
      in total patient-years (beta = 80%; alpha one-sided = 0.025). The Caravaggio
      study has the potential, along with other recently performed or on-going studies,
      to make less cumbersome the management of VTE in patients with cancer by
      replacing parenteral with oral anticoagulation.

PMID- 30103253
TI  - Sex differences in the effect of cannabinoid type 1 receptor deletion on locus
      coeruleus-norepinephrine neurons and corticotropin releasing factor-mediated
      responses.
AB  - Cannabinoids are capable of modulating mood, arousal, cognition and behavior, in
      part via their effects on the noradrenergic nucleus locus coeruleus (LC).
      Dysregulation of LC signaling and norepinephrine (NE) efflux in the medial
      prefrontal cortex (mPFC) can lead to the development of psychiatric disorders,
      and CB1r deletion results in alterations of alpha2- and beta1-adrenoceptors in
      the mPFC, suggestive of increased LC activity. To determine how CB1r deletion
      alters LC signaling, whole-cell patch-clamp electrophysiology was conducted in LC
      NE neurons of male and female wild type (WT) and CB1r-knock out (KO) mice. CB1r
      deletion caused a significant increase in LC-NE excitability and input resistance
      in male but not female mice when compared to WT. CB1r deletion also caused
      adaptations in several indices of noradrenergic function. CB1r/CB2r-KO male mice
      had a significant increase in cortical NE levels and tyrosine hydroxylase and CRF
      levels in the LC compared to WT males. CB1r/CB2r-KO female mice showed a
      significant increase in LC alpha2-AR levels compared to WT females. To further
      probe actions of the endocannabinoid system as an anti-stress neuromediator, the
      effect of CB1r deletion on CRF-induced responses in the LC was investigated. The
      increase in LC-NE excitability observed in male and female WT mice following CRF
      (300 nM) bath application was not observed in CB1r-KO mice. These results
      indicate that cellular adaptations following CB1r deletion cause a disruption in
      LC-NE signaling in males but not females, suggesting underlying sex differences
      in compensatory mechanisms in KO mice as well as basal endocannabinoid regulation
      of LC-NE activity.

PMID- 30103254
TI  - Radiotherapy for the treatment of distant nodes metastases from oligometastatic
      urothelial cancer: A retrospective case series.
AB  - OBJECTIVES: To investigate the efficacy of stereotactic body radiotherapy in
      oligometastatic urothelial carcinoma with node-only involvement. METHODS: We
      retrospectively collected data on the outcomes of patients who underwent
      stereotactic body radiotherapy for metastatic node lesions from oligometastatic
      urothelial carcinoma at Radiotherapy Unit of University Hospital of Parma, Parma,
      Italy. The investigated outcomes were lesion size, standardized uptake value,
      overall response rate, lesion control rate, lesion progression-free interval,
      progression-free survival and overall survival. RESULTS: Among seven patients
      included in the study, a total of 14 node metastatic lesions were treated with
      stereotactic body radiotherapy. The mean total dose of stereotactic body
      radiotherapy was 32 Gy (range 25-40 Gy). At first imaging evaluation, a mean
      variation of -4% (P = 0.427) in major diameter, -16% (P = 0.048) in minor
      diameter and -76% in standardized uptake value (P < 0.001) were documented. The
      overall response rate and lesion control rate were 43% and 100%, respectively.
      Median lesion progression-free interval, progression-free survival and overall
      survival were 11.4 months (95% CI 3.4-19.4), 2.9 months (95% CI 2.6-3.1) and 14.9
      months (95% CI 12.3-17.5), respectively. Stereotactic body radiotherapy was
      effective in delaying the beginning of a systemic chemotherapy in four patients.
      CONCLUSIONS: The present findings generate the hypothesis of a possible role for
      the use of stereotactic body radiotherapy in selected patients with distant node
      metastases from oligometastatic urothelial carcinoma.

PMID- 30103255
TI  - Early use of steroid-sparing agents in the inactivation of moderate-to-severe
      active thyroid eye disease: a step-down approach.
AB  - OBJECTIVES: The current first-line treatment for management of active thyroid eye
      disease (TED) is high-dose intravenous corticosteroids, which have the potential
      for serious adverse effects. Our aim was to evaluate the effect of steroid
      sparing agents (SSAs) in patients with moderate-to-severe active TED, using
      methotrexate as first-line. METHODS: Presented is a retrospective, four-year,
      single-centre, consecutive case series of patients with moderate-to-severe TED
      treated using the Oxford protocol. Treatment modality, disease activity, and
      adverse effects are reported at presentation, 6- and 12-month follow-up. RESULTS:
      104 consecutive TED patients treated by the Oxford TED team were reviewed. 24
      patients with moderate-to-severe active disease were identified (mean age 46.8
      years;12 female) with a mean pretreatment VISA inflammatory index score of 5.5/10
      (SD = 1.98; range 1-9). Intravenous methyl-prednisolone (IVMP) and an SSA was
      commenced in all patients. Mean total steroid dose was 2.72 g (SD = 1.4;1.0-6.9).
      38% of patients (n = 9) received <=1.5 g of IVMP. Only two patients required >4.5
      g of IVMP equating to the EUGOGO treatment protocol dose for this patient group.
      There was significant improvement in inflammatory index score both at the
      intermediate review (mean score 2.7; SD = 2.8; P < 0.001; mean follow up 25.2
      weeks) and at one year or last follow-up (mean score 1.4; SD = 1.5; P < 0.001;
      mean follow up 48.0 weeks). No serious or long-term adverse effects were
      reported. CONCLUSION: This study suggests that the initiation of an SSA, using
      methotrexate as first-line, with limited adjuvant IVMP is an effective and safe
      treatment for moderate-to-severely active TED, resulting in a significant
      reduction in both disease activity and total steroid load.

PMID- 30103256
TI  - Impact of thyroid surgery volume and pathologic detection on risk of thyroid
      cancer: A geographical analysis in the Rhone-Alpes region of France.
AB  - OBJECTIVE: To investigate the impact of the volume of thyroid surgery and
      pathologic detection on the risk of thyroid cancer. METHODS: We investigated the
      influence of the volume of thyroid surgery in a first study that included 23 384
      thyroid surgeries and 5302 thyroid cancers collected between 2008 and 2013.
      Standardized incidence ratios (SIRs) and thyroid intervention rates (STIRs) were
      used as indicators of cancer risk and surgery volume, respectively. The influence
      of pathologic detection, using the number of cuts per gram of tissue as the
      indicator, was studied in a second study that included 1257 thyroid specimens,
      collected in 2014. RESULTS: We found departmental variations in SIRs and a
      significant effect of the STIR on the SIR (men, P = 0.0008; women, P < 0.0001). A
      1/100 000 increase in the STIR resulted in a 3% and 1.3% increase in the SIR in
      men and women, respectively. This effect was greatest for microcancers and absent
      for tumours >4 cm. The risk of cancer diagnosis was significantly associated with
      the number of cuts per gram of tissue (OR 6.1, P < 0.001), and was greater for
      total thyroidectomy than for lobectomy (P = 0.014) and when FNA cytology had been
      preoperatively performed (P < 0.001). The prevalence of incidental microcancers
      was highest in the centres performing the highest number of cuts per gram.
      CONCLUSIONS: The risk of thyroid cancer, particularly microcancer, is related to
      the volume of surgery and to the level of pathologist scrutiny. Both factors
      contribute to the increase in overdiagnosis. This further advocates for
      appropriate selection of patients for thyroid surgery.

PMID- 30103257
TI  - Microbiological Decontamination of Water: Improving the Solar Disinfection
      Technique (SODIS) with the Use of Nontoxic Vital Dye Methylene Blue.
AB  - Rational use of water is a major challenge for governments and global
      organizations, with easy and inexpensive interventions being sought by
      communities that are not supplied with drinking water. In this context, solar
      disinfection (SODIS) has shown great efficiency for water disinfection. To speed
      up the process and improve inactivation, we studied the effects of methylene blue
      (MB) as a photodynamic agent because of its ability to absorb visible light (red
      wavelength) and generate singlet oxygen as a reactive species, thereby
      inactivating bacteria and viruses present in water. In this study, samples of
      clean mineral water were artificially contaminated with Gram-positive
      (Staphylococcus epidermidis or Deinococcus radiodurans) or with Gram-negative
      strains (Escherichia coli or Salmonella typhimurium) and exposed to traditional
      SODIS or to MB-SODIS. A lethal synergistic effect was observed when cultures were
      illuminated in the presence of MB. The obtained results indicate that bacterial
      inactivation can be achieved in a much shorter time when using MB associated with
      SODIS treatment. Therefore, this technique was able to provide safe water for
      consumption through the inactivation of microorganisms in general, including
      pathogens and some strains resistant to the traditional SODIS procedure, thus
      allowing its use in areas usually less exposed to sunlight.

PMID- 30103258
TI  - Novel NR5A1 mutations found in Chinese patients with 46, XY disorders of sex
      development.
AB  - OBJECTIVE: To analyze nuclear receptor subfamily 5 group A member 1 (NR5A1) gene
      mutations in a cohort of Chinese patients with 46, XY Disorders of Sex
      Development (DSD). METHODS: Sixty 46, XY DSD patients were recruited at Peking
      Union Medical College Hospital. Targeted next-generation and Sanger sequencing
      were performed to investigate pathogenic gene variants and validate NR5A1 gene
      variants, respectively. In silico tools and in vitro function studies were used
      to analyze the pathogenicity of rare variants. The clinical and endocrinological
      characteristics of patients with NR5A1 variants were retrospectively analyzed.
      RESULTS: A total of four novel and three recurrent NR5A1 variants were identified
      in seven 46, XY DSD patients. These variants widely spread almost all the
      functional domains. Functional studies showed that novel mutations including
      p.S32N, p.N44del and p.G91D reduced transactivation of CYP11A1, while the other
      missense variant p.A168E did not impact protein function. All patients with NR5A1
      rare variants had normal adrenal function and showed genital defects. Results of
      the genitalia examination showed female external genitalia (three patients),
      ambiguous external genitalia (two patients), female external genitalia with
      clitoromegaly (one patient), and hypospadias (one patient). All seven patients
      had bilateral testis and five of seven patients lacked Mullerian structures.
      CONCLUSIONS: Four novel mutations in the NR5A1 gene were identified in our cohort
      with 46, XY DSD, expanding the spectrum of NR5A1 gene mutations. All patients
      with NR5A1 rare variants had normal adrenal function and showed genital defects.

PMID- 30103259
TI  - Isolation and characterization of a highly pathogenic strain of Porcine enteric
      alphacoronavirus causing watery diarrhoea and high mortality in newborn piglets.
AB  - Porcine enteric alphacoronavirus (PEAV) was first discovered in China in February
      2017, and the origin and virulence of this novel porcine coronavirus were not
      fully characterized. Here, we isolated a strain of PEAV, named GDS04 that is
      identified by immunofluorescence and typical crown-shaped particles observed with
      electron microscopy. Genomic analysis reveals that PEAV GDS04 shares a close
      relationship with SADS-CoV and SeACoV. Furthermore, newborn piglets orally
      challenged with PEAV GDS04 developed typical clinical symptoms as watery
      diarrhoea in neonatal piglets. Viral RNA was detected in faeces and various
      tissues of the infected piglets. Moreover, macroscopic and microscopic lesions in
      whole intestinal tract were observed, and viral antigen could be detected in the
      small intestines by immunohistochemical staining and electron microscopy.
      Importantly, the mortality rate of inoculated-newborn piglets was 100% and half
      of the cohabiting piglets died. Collectively, we demonstrate that PEAV is highly
      pathogenic in newborn piglets.

PMID- 30103260
TI  - Dedifferentiation, transdifferentiation and cell fusion: in vivo reprogramming
      strategies for regenerative medicine.
AB  - Regenerative capacities vary enormously across the animal kingdom. In contrast to
      most cold-blooded vertebrates, mammals, including humans, have very limited
      regenerative capacity when it comes to repairing damaged or degenerating tissues.
      Here, we review the main mechanisms of tissue regeneration, underlying the
      importance of cell dedifferentiation and reprogramming. We discuss the
      significance of cell fate and identity changes in the context of regenerative
      medicine, with a particular focus on strategies aiming at the promotion of the
      body's self-repairing mechanisms. We also introduce some of the most recent
      advances that have resulted in complete reprogramming of cell identity in vivo.
      Lastly, we discuss the main challenges that need to be addressed in the near
      future to develop in vivo reprogramming approaches with therapeutic potential.

PMID- 30103261
TI  - Discriminating between empirical studies and nonempirical works using automated
      text classification.
AB  - OBJECTIVE: Identify the most performant automated text classification method (eg,
      algorithm) for differentiating empirical studies from nonempirical works in order
      to facilitate systematic mixed studies reviews. METHODS: The algorithms were
      trained and validated with 8050 database records, which had previously been
      manually categorized as empirical or nonempirical. A Boolean mixed filter
      developed for filtering MEDLINE records (title, abstract, keywords, and full
      texts) was used as a baseline. The set of features (eg, characteristics from the
      data) included observable terms and concepts extracted from a metathesaurus. The
      efficiency of the approaches was measured using sensitivity, precision,
      specificity, and accuracy. RESULTS: The decision trees algorithm demonstrated the
      highest performance, surpassing the accuracy of the Boolean mixed filter by 30%.
      The use of full texts did not result in significant gains compared with title,
      abstract, keywords, and records. Results also showed that mixing concepts with
      observable terms can improve the classification. SIGNIFICANCE: Screening of
      records, identified in bibliographic databases, for relevant studies to include
      in systematic reviews can be accelerated with automated text classification.

PMID- 30103262
TI  - Fully automated and integrated multiplex detection of high consequence livestock
      viral genomes on a microfluidic platform.
AB  - Differential diagnosis of diseases that share common clinical signs typically
      requires the performance of multiple independent diagnostic tests to confirm
      diagnosis. Diagnostic tests that can detect and discriminate between multiple
      differential pathogens in a single reaction may expedite, reduce costs, and
      streamline the diagnostic testing workflow. Livestock haemorrhagic diseases like
      classical swine fever (CSF), African swine fever (ASF), and vesicular diseases,
      such as foot-and-mouth disease (FMD), vesicular stomatitis (VS), and swine
      vesicular disease (SVD) can have an enormous impact on the livestock industry and
      economy of countries that were previously free of the diseases. Thus, rapid
      diagnosis of these diseases is critical for disease control. Here, we describe
      the development and initial laboratory validation of a novel fully automated user
      developed assay for simultaneous detection and differentiation of multiple
      viruses of veterinary importance in a single reaction with minimal user
      intervention. The user only performs sample loading, placement of consumables and
      reagents, selection and initiation of assay while all other processes (i.e.,
      nucleic acid extraction, multiplex RT-PCR, reverse dot blot detection and result
      reporting) are performed fully automated. The current assay has a turn-around
      time of approximately 6 hr and can simultaneously process up to 24 samples. The
      automated assay accurately and specifically detected 37 laboratory amplified
      strains of the five target viruses, including all seven serotypes of FMD virus,
      three genotypes of CSF virus, and two serotypes of VS virus. The assay also
      detected targeted viruses in a variety of clinical samples collected from
      infected animals, such as oral fluid, oral swab, nasal swab, whole blood, serum,
      as well as tonsil, spleen, kidney, and ileum. No cross-reactivity was observed
      with 15 nontarget viruses that affect livestock and samples from clinically
      healthy animals. To our knowledge, this is the first fully automated and
      integrated assay for simultaneous detection of multiple high consequence
      veterinary pathogens.

PMID- 30103263
TI  - Treatments for women with gestational diabetes mellitus: an overview of Cochrane
      systematic reviews.
AB  - BACKGROUND: Successful treatments for gestational diabetes mellitus (GDM) have
      the potential to improve health outcomes for women with GDM and their babies.
      OBJECTIVES: To provide a comprehensive synthesis of evidence from Cochrane
      systematic reviews of the benefits and harms associated with interventions for
      treating GDM on women and their babies. METHODS: We searched the Cochrane
      Database of Systematic Reviews (5 January 2018) for reviews of
      treatment/management for women with GDM. Reviews of pregnant women with pre
      existing diabetes were excluded.Two overview authors independently assessed
      reviews for inclusion, quality (AMSTAR; ROBIS), quality of evidence (GRADE), and
      extracted data. MAIN RESULTS: We included 14 reviews. Of these, 10 provided
      relevant high-quality and low-risk of bias data (AMSTAR and ROBIS) from 128
      randomised controlled trials (RCTs), 27 comparisons, 17,984 women, 16,305 babies,
      and 1441 children. Evidence ranged from high- to very low-quality (GRADE). Only
      one effective intervention was found for treating women with
      GDM.EffectiveLifestyle versus usual careLifestyle intervention versus usual care
      probably reduces large-for-gestational age (risk ratio (RR) 0.60, 95% confidence
      interval (CI) 0.50 to 0.71; 6 RCTs, N = 2994; GRADE moderate-quality).PromisingNo
      evidence for any outcome for any comparison could be classified to this
      category.Ineffective or possibly harmful Lifestyle versus usual careLifestyle
      intervention versus usual care probably increases the risk of induction of labour
      (IOL) suggesting possible harm (average RR 1.20, 95% CI 0.99 to 1.46; 4 RCTs, N =
      2699; GRADE moderate-quality).Exercise versus controlExercise intervention versus
      control for return to pre-pregnancy weight suggested ineffectiveness (body mass
      index, BMI) MD 0.11 kg/m2, 95% CI -1.04 to 1.26; 3 RCTs, N = 254; GRADE moderate
      quality).Insulin versus oral therapyInsulin intervention versus oral therapy
      probably increases the risk of IOL suggesting possible harm (RR 1.3, 95% CI 0.96
      to 1.75; 3 RCTs, N = 348; GRADE moderate-quality).Probably ineffective or harmful
      interventionsInsulin versus oral therapyFor insulin compared to oral therapy
      there is probably an increased risk of the hypertensive disorders of pregnancy
      (RR 1.89, 95% CI 1.14 to 3.12; 4 RCTs, N = 1214; GRADE moderate
      quality).InconclusiveLifestyle versus usual careThe evidence for childhood
      adiposity kg/m2 (RR 0.91, 95% CI 0.75 to 1.11; 3 RCTs, N = 767; GRADE moderate
      quality) and hypoglycaemia was inconclusive (average RR 0.99, 95% CI 0.65 to
      1.52; 6 RCTs, N = 3000; GRADE moderate-quality).Exercise versus controlThe
      evidence for caesarean section (RR 0.86, 95% CI 0.63 to 1.16; 5 RCTs, N = 316;
      GRADE moderate quality) and perinatal death or serious morbidity composite was
      inconclusive (RR 0.56, 95% CI 0.12 to 2.61; 2 RCTs, N = 169; GRADE moderate
      quality).Insulin versus oral therapyThe evidence for the following outcomes was
      inconclusive: pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 RCTs, N = 2060),
      caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 RCTs, N = 1988), large-for
      gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 RCTs, N = 2352), and
      perinatal death or serious morbidity composite (RR 1.03; 95% CI 0.84 to 1.26; 2
      RCTs, N = 760). GRADE assessment was moderate-quality for these outcomes.Insulin
      versus dietThe evidence for perinatal mortality was inconclusive (RR 0.74, 95% CI
      0.41 to 1.33; 4 RCTs, N = 1137; GRADE moderate-quality).Insulin versus insulinThe
      evidence for insulin aspart versus lispro for risk of caesarean section was
      inconclusive (RR 1.00, 95% CI 0.91 to 1.09; 3 RCTs, N = 410; GRADE moderate
      quality).No conclusions possibleNo conclusions were possible for: lifestyle
      versus usual care (perineal trauma, postnatal depression, neonatal adiposity,
      number of antenatal visits/admissions); diet versus control (pre-eclampsia,
      caesarean section); myo-inositol versus placebo (hypoglycaemia); metformin versus
      glibenclamide (hypertensive disorders of pregnancy, pregnancy-induced
      hypertension, death or serious morbidity composite, insulin versus oral therapy
      (development of type 2 diabetes); intensive management versus routine care (IOL,
      large-for-gestational age); post- versus pre-prandial glucose monitoring (large
      for-gestational age). The evidence ranged from moderate-, low- and very low
      quality. AUTHORS' CONCLUSIONS: Currently there is insufficient high-quality
      evidence about the effects on health outcomes of relevance for women with GDM and
      their babies for many of the comparisons in this overview comparing treatment
      interventions for women with GDM. Lifestyle changes (including as a minimum
      healthy eating, physical activity and self-monitoring of blood sugar levels) was
      the only intervention that showed possible health improvements for women and
      their babies. Lifestyle interventions may result in fewer babies being large.
      Conversely, in terms of harms, lifestyle interventions may also increase the
      number of inductions. Taking insulin was also associated with an increase in
      hypertensive disorders, when compared to oral therapy. There was very limited
      information on long-term health and health services costs. Further high-quality
      research is needed.

PMID- 30103265
TI  - TLR7-let-7 Signaling Contributes to Ethanol-Induced Hepatic Inflammatory Response
      in Mice and in Alcoholic Hepatitis.
AB  - BACKGROUND: Toll-like receptor 7 (TLR7) is an endosomal TLR that is activated by
      single-stranded RNA, including endogenous microRNAs (e.g., let-7b). Increased
      hepatic expression of TLRs, microRNAs, and inflammatory mediators is linked to
      ethanol (EtOH) exposure and to alcoholic liver disease (ALD). ALD invovles
      chronic hepatic inflammation that can progress to alcoholic hepatitis (AH), a
      particularly severe form of ALD. This study aimed to investigate TLR7 expression
      in patients with different liver disease phenotypes and in mouse liver following
      alcohol exposure. METHODS: Hepatic mRNA expression was determined by RNA
      sequencing of liver tissue from patients with liver disease or normal liver
      tissue. Mice were exposed to subchronic EtOH followed by administration of the
      TLR7 agonist imiquimod. Primary human hepatocytes were exposed to EtOH or
      imiquimod in vitro. RESULTS: RNAseq analysis revealed that hepatic expression of
      TLR7 and let-7b microRNA, an endogenous TLR7 ligand, was significantly increased
      in AH patients. Hepatic expression of TLR7 and let-7b positively correlated with
      hepatic IL-8 mRNA expression. In mice, EtOH increased hepatic TLR7 mRNA
      expression and enhanced imiquimod-induced expression of the pro-inflammatory
      mediators TNFalpha, MCP-1, and iNOS. In vitro, EtOH significantly increased
      hepatocyte TLR7 mRNA and the TLR7 agonist, imiquimod, induced hepatocyte
      expression of TNFalpha and IL-8 mRNA. EtOH also increased the release of let-7b
      in microvesicles from hepatocytes, suggesting that EtOH can increase the
      expression of both the receptor and its endogenous ligand. CONCLUSIONS: These
      studies suggest that increased TLR7 signaling caused by increased expression of
      TLR7 and its endogenous ligand let-7b may contribute to the enhanced inflammatory
      response associated with AH.

PMID- 30103264
TI  - Psychological burden of pediatric primary immunodeficiency.
AB  - BACKGROUND: Primary immunodeficiency disorder (PID), being a chronic disorder,
      may increase the prevalence of psychopathologies, but there are few studies on
      the effect of disease-related factors on psychopathology in this population. The
      aim of this study was therefore to assess and compare three groups: children with
      PID who receive i.v. immunoglobulin treatment; children with juvenile idiopathic
      arthritis (JIA); and healthy controls with respect to their mental health status.
      METHODS: Forty-four children with PID, 32 children with JIA and 30 healthy
      controls, underwent psychiatric evaluation. The Childhood Depression Inventory
      and the screen for child anxiety-related emotional disorders questionnaire were
      completed by the participants. The child behavior checklist was completed by the
      mothers of the participants. In addition, disease-related factors were
      identified. RESULTS: The frequency of mood disorders between the three groups
      differed. There was no difference between the PID and JIA groups with respect to
      the prevalence of mood disorders and other psychopathologies. The disease-related
      factors were associated with the frequency of mood disorder in PID patients.
      CONCLUSION: The rate of psychopathology was similar in patients with PID and JIA
      and higher than the controls. Some of the disease-related factors were associated
      with the frequency of mood disorders in the PID patients.

PMID- 30103266
TI  - Depression among military spouses: Demographic, military, and service member
      psychological health risk factors.
AB  - BACKGROUND: More than a decade of war has strained service members and their
      families and the psychological health of military spouses is a concern. This
      study uses data from the largest study of military families in the United States
      to examine the demographic, military-specific, and service member mental health
      correlates of probable diagnosis of major depressive disorder (MDD) among
      military spouses. METHODS: Data were from service member-spouse dyads from all
      branches of the U.S. military. Demographic and military-specific factors were
      assessed using administrative personnel records and survey data. RESULTS: Of the
      9,038 spouses, 4.9% had a probable diagnosis of MDD. In unadjusted models,
      spouses of service members who deployed and experiencecd combat-related events,
      were enlisted, had a probable posttraumatic stress disorder (PTSD) diagnosis, or
      screened positive for alcohol misuse were more likely to screen positive for MDD.
      In adjusted models, only spouses married to enlisted service members or those
      with PTSD had increased risk for MDD. Other demographic and military-related
      factors associated with MDD in spouses included less educational attainment,
      unemployment, having four or more children, and having prior military service
      (although not currently serving in the military) in the adjusted models.
      CONCLUSIONS: Findings characterize demographic, military, and service member
      psychological health factors that are associated with depression among military
      spouses. These findings imply that deployment alone may not negatively affect
      military spouses, but rather it may be the mental health impact on the service
      member, especially PTSD that increases the odds for MDD among military spouses.

PMID- 30103267
TI  - New resistance mutations to nucleoside reverse transcriptase inhibitors at codon
      184 of HIV-1 reverse transcriptase (M184L and M184T).
AB  - Mutations at HIV-1 reverse transcriptase (RT) codon 184 such as M184V confer
      resistance to two nucleos(t)ide RT inhibitors (NRTI), lamivudine (3TC) and
      emtricitabine (FTC). The prevalence of mutations at HIV-1 RT codon 184 was
      evaluated using three independent RT sequence databases from treatment
      experienced (TE) and treatment-naive (TN) individuals. Data were collected
      retrospectively from three centers: one in Italy and two in France between 1997
      and 2016. In order to highlight the role of these mutations in conferring drug
      resistance, structural and thermodynamic analyses were conducted by means of
      computational approaches. Among 32,440 RT sequences isolated from TE and 12,365
      isolated from TN patients, the prevalence of HIV-1 RT codon 184 substitutions in
      each group was 31.21% and 0.72%, respectively. The mutations M184L and M184T have
      been observed only in TE patients. In all cases but four, M184L and M184T
      mutations were present during NRTI treatment. Molecular recognition studies on
      M184L and M184T structures showed both FTC and 3TC thermodynamic profiles
      unfavorable in comparison with the wild-type sequence, corroborated by molecular
      dynamic simulations (MDS). In this study, we highlighted two new resistance
      mutations in vivo for NRTI resistance. The low frequency of this pathway can be
      related to high impairment of replicative capacity mediated by these mutations.

PMID- 30103268
TI  - Implementing an early childhood oral health program in a federally qualified
      health center in North Carolina.
AB  - OBJECTIVES: To examine the Baby Oral Health Program's (bOHP) influence on dental
      visits for children 0 to 3 years and overall dental visits in four federally
      qualified health center (FQHC) clinics. METHODS: Using an interrupted time series
      study design, administrative data were obtained for the year prior and following
      the intervention. The intervention included dental staff training on early
      childhood oral health, quality improvement, and monthly visits during the follow
      up intervention period. Analysis included descriptive and segmented regression
      using aggregate patient visit data. RESULTS: A total of 10,400 patients made
      26,416 visits over the study period; 1,187 (11 percent) were children <=3 years.
      Visit counts in the youngest age group increased 70 percent following the
      intervention. When controlling for the naturally increasing trend, the
      intervention added 8.7 (95 percent CI: 4.7, 12.8) early childhood patient-visits
      per clinic in the last month of the intervention period. The increase in visit
      counts in the youngest age group had no significant effect on other ages, except
      for a decline relative to the natural trend in patient-visits among 35-50 year
      olds (-32.3 less visits) following the intervention. The proportion of visits for
      all ages by <=3 year olds increased from 5 to 8 percent following the
      intervention. CONCLUSIONS: bOHP increased dental visits among children <=3 years
      but the finding might be attributable to clinic changes coinciding with bOHP
      implementation that were not controlled with the study design. Additional studies
      are needed in populations experiencing challenges accessing dental care.

PMID- 30103269
TI  - ChemFrag: Chemically meaningful annotation of fragment ion mass spectra.
AB  - Identification and structural determination of small molecules by mass
      spectrometry is an important step in chemistry and biochemistry. However, the
      chemically realistic annotation of a fragment ion spectrum can be a difficult
      challenge. We developed ChemFrag, for the detection of fragmentation pathways and
      the annotation of fragment ions with chemically reasonable structures. ChemFrag
      combines a quantum chemical with a rule-based approach. For different doping
      substances as test instances, ChemFrag correctly annotates fragment ions. In most
      cases, the predicted fragments are chemically more realistic than those from
      purely combinatorial approaches, or approaches based on machine learning. The
      annotation generated by ChemFrag often coincides with spectra that have been
      manually annotated by experts. This is a major advance in peak annotation and
      allows a more precise automatic interpretation of mass spectra.

PMID- 30103270
TI  - Genomic screening of Fabry disease in young stroke patients: the Taiwan
      experience and a review of the literature.
AB  - BACKGROUND AND PURPOSE: Fabry disease is an X-linked disease, and enzyme-based
      screening methods are not suitable for female patients. METHODS: In total, 1000
      young stroke patients (18-55 years, 661 with ischaemic stroke and 339 with
      hypertensive intracerebral hemorrhage) were recruited. The Sequenom iPLEX assay
      was used to detect 26 Fabry related mutation genes. The frequency of Fabry
      disease in young stroke was reviewed and compared between Asian and non-Asian
      countries. RESULTS: Two male patients with ischaemic stroke were found to have a
      genetic mutation of IVS4+919G>A. There was no alpha-galactosidase A (GLA) gene
      mutation in female patients. The frequency in Asian stroke patients was 0.62%
      (male vs. female 0.63% vs. 0.58%) with 0.72% for ischaemic stroke and none for
      hemorrhagic stroke, compared to 0.88% (0.77% vs. 1.08%) with 0.83% for ischaemic
      stroke and 1.40% for hemorrhagic stroke reported in western countries.
      CONCLUSION: IVS4+919G>A is the GLA mutation in Taiwanese young ischaemic stroke
      patients. Fabry disease is more frequent among non-Asian patients compared to
      Asian patients.

PMID- 30103271
TI  - Prognostic role of the preoperative serum albumin : globulin ratio after radical
      nephroureterectomy for upper tract urothelial carcinoma.
AB  - OBJECTIVES: To elucidate the effects of the preoperative albumin : globulin ratio
      on the survival of patients with upper tract urothelial carcinoma after radical
      nephroureterectomy. METHODS: We retrospectively reviewed 124 consecutive patients
      with upper tract urothelial carcinoma who underwent radical nephroureterectomy at
      Chiba Cancer Center, Chiba, Japan between 2002 and 2015. The albumin : globulin
      ratio was defined: albumin / (total protein - albumin). Associations between
      preoperative clinicopathological factors, including the albumin : globulin ratio,
      and recurrence-free survival, cancer-specific survival and overall survival were
      assessed. The log-rank test and Cox proportional hazards models were used for
      univariate and multivariable analyses, respectively. The study cohort was
      separated into two groups based on the optimal albumin : globulin ratio cut-off
      value determined using receiver operating characteristic curve analysis. RESULTS:
      The median survival time was 55 months (interquartile range 28-76 months), and 31
      patients died during follow up. A low preoperative albumin : globulin ratio <1.40
      was associated with tumor grade and surgical margin status. Kaplan-Meier analyses
      showed that a low albumin : globulin ratio was more significantly correlated with
      worse recurrence-free survival, cancer-specific survival and overall survival.
      Multivariate analyses showed that a low albumin : globulin ratio was an
      independent predictive factor associated with poor recurrence-free survival
      (hazard ratio 3.758; P = 0.0028), cancer-specific survival (hazard ratio 5.687; P
      = 0.0044) and overall survival (hazard ratio 3.124; P = 0.0030). CONCLUSIONS: A
      low albumin : globulin ratio is an independent predictive factor associated with
      poor prognosis in upper tract urothelial carcinoma patients treated with radical
      nephroureterectomy.

PMID- 30103272
TI  - Plexiform fibromyxoma of the stomach: Fine needle aspiration cytology and
      histological correlation.

PMID- 30103273
TI  - Long-term plasticity of glutamatergic input from the subthalamic nucleus to the
      entopeduncular nucleus.
AB  - The hyperdirect pathway of the basal ganglia bypasses the striatum, and delivers
      cortical information directly to the subthalamic nucleus (STN). In rodents, the
      STN excites the two output nuclei of the basal ganglia, the entopeduncular
      nucleus (EP) and the substantia nigra reticulata (SNr). Thus, during hyperdirect
      pathway activation, the STN drives EP firing inhibiting the thalamus. We
      hypothesized that STN activity could induce long-term changes to the STN->EP
      synapse. To test this hypothesis, we recorded in the whole-cell mode from neurons
      in the EP in acute brain slices from rats while electrically stimulating the STN.
      Repetitive pre-synaptic stimulation generated modest long-term depression (LTD)
      in the STN->EP synapse. However, pairing EP firing with STN stimulation generated
      robust LTD that manifested for pre-before post-as well as for post- before pre
      synaptic pairing. This LTD was highly sensitive to the time difference and was
      not detected at a time delay of 10 ms. To investigate whether post-synaptic
      calcium levels were important for LTD induction, we made dendritic recordings
      from EP neurons that revealed action potential back-propagation and dendritic
      calcium transients. Buffering the dendritic calcium concentration in the EP
      neurons with EGTA generated long term potentiation instead of LTD. Finally, mild
      LTD could be induced by post-synaptic activity alone that was blocked by an
      endocannabinoid 1 (CB1) receptor blocker. These results thus suggest there may be
      an adaptive mechanism for buffering the impact of the hyperdirect pathway on
      basal ganglia output which could contribute to the de-correlation of STN and EP
      firing.

PMID- 30103274
TI  - Editorial Comment from Dr Safwat to Risk of urinary stones among women with
      pelvic organ prolapse: A national population-based cohort study.

PMID- 30103275
TI  - Quercetin in Food: Possible Mechanisms of Its Effect on Memory.
AB  - Quercetin (3,3',4',5,7-pentahydroxyflavone) is found in vegetables and fruits. It
      is one of the major flavonoids that is part of human diets. Quercetin has several
      pharmacological effects in the nervous system as a neuroprotective agent. In this
      review, we summarize the research on quercetin and its role in memory in both
      animals and humans. Articles were chosen from the Scopus, PubMed, and Web of
      Science databases. In this review, we describe and summarize the importance of
      quercetin's presence in the body, particularly in the brain; its kinetics,
      including its absorption, metabolism, distribution, and excretion; its behavioral
      effects; and some of the possible mechanisms of action of quercetin on memory in
      different animal models. Several important pathways that may be involved in the
      processes of learning and memory, long-term potentiation, and cognition may be
      impaired during neurological diseases or other medical conditions. As dietary
      quercetin is important, provision of its best formulation for delivery to the
      brain as a nutraceutical and in clinical translational research for the
      prevention or treatment of Alzheimer's disease and other types of dementia is
      necessary.

PMID- 30103276
TI  - Language matters: a UK perspective.
AB  - AIM: To review the existing evidence regarding the use of language in clinical
      encounters. BACKGROUND: Awareness of the importance of language in clinical
      encounters is mostly lacking or located within broader discussions on
      communication. METHODS: A scoping study was conducted to review existing research
      that could increase our understanding of the role language plays as well as
      identify gaps in knowledge and inform the development of a position statement on
      language in diabetes care. RESULTS: Evidence shows that, although carefully
      chosen language can have a positive effect, there is a potential negative impact
      of language on people's experiences of diabetes care. The use of stigmatizing and
      discriminatory words during communication between healthcare practitioners and
      people with diabetes can lead to disengagement with health services as well as
      sub-optimal diabetes self-management. Clinical encounters can be compromised
      where language barriers exist or where there is limited understanding of cultural
      differences that may have an impact on diabetes self-management. What little
      empirical evidence there is shows that training can improve language and
      communication skills. CONCLUSION: This review raises a number of questions that
      are being addressed by the NHS England Language Matters Group, which has
      developed a set of recommendations to support the use of appropriate language in
      clinical encounters.

PMID- 30103277
TI  - Hypertension and heart disease are associated with development of brain atrophy
      in multiple sclerosis: a 5-year longitudinal study.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) are more frequent in multiple
      sclerosis (MS) patients when compared to controls. In particular, CVDs are linked
      with higher accumulation of lesions and advanced brain atrophy. OBJECTIVE: To
      investigate whether CVDs contribute to accelerated lesion accumulation and brain
      atrophy over 5 years in patients with MS. METHODS: 194 MS patients and 43
      controls without neurologic disease were followed for 5 years. Full physical,
      neurological evaluation, and structured questionnaire investigating CVD and risk
      factors (hypertension, hyperlipidemia, heart disease, smoking, diabetes,
      obesity/overweight) were collected using interview-based questionnaire and
      further cross-reference with electronic medical records. Lesion and brain atrophy
      outcomes were assessed with 3T MRI. ANCOVA adjusted for age, gender, and disease
      duration were used accordingly. False discovery rate correction was performed
      using Benjamini-Hochberg correction. RESULTS: Patients with diagnosis of heart
      disease showed higher white matter and whole brain volume loss compared to those
      without (-4.2% vs. -0.7%, P = 0.01 and -3.4% vs. -1.6%, P = 0.01, respectively).
      The percentage lateral ventricle volume change in MS patients with hypertension
      was higher compared to non-hypertensive patients (24.5% vs. 14.1%, P = 0.05).
      Hyperlipidemia, smoking, and obesity/overweight were not associated with
      progression of MRI-derived outcomes. CVDs did not contribute to larger lesion
      volume accrual over the 5-year period. The presence of CVDs was not associated
      with MRI-derived changes in the controls. CONCLUSIONS: Hypertension and heart
      disease contribute to advanced brain atrophy in MS patients. CVDs did not
      contribute to additional lesion accrual. CVD comorbidities in MS patients may
      contribute to neurodegenerative tissue injury that can be detected with brain
      MRI.

PMID- 30103278
TI  - Ice water test in multiple sclerosis: A pilot trial.
AB  - OBJECTIVES: To investigate the significance of the ice water test in patients
      with multiple sclerosis and to evaluate a novel ice water test nomogram in a
      large patient cohort. METHODS: A total of 201 ice water tests of patients with
      multiple sclerosis were retrospectively evaluated. Incontinence episodes in 24 h
      and sex were correlated with the ice water test. Furthermore, an ice water test
      nomogram was developed in order to categorize the detrusor overactivity in
      severity degrees. Descriptive statistics were carried out for population
      characteristics. Correlations of categorical variables were calculated by the
      chi2 -test. The independent t-test was carried out for correlations of continuous
      variables. Furthermore, the data were evaluated in the novel ice water test
      nomogram. RESULTS: The patient population consisted of 141 (70.1%) women and 60
      (39.9%) men. A clinically positive ice water test (maximum detrusor pressure >15
      cmH2 O) was identified in 75 patients (37.3%). Significantly more men presented a
      clinically positive ice water test (P = 0.006). In 16.5%, the ice water test
      unmasked an involuntary detrusor contraction, although routine cystometry did not
      show any detrusor overactivity. The ice water test nomogram could be successfully
      applied. The incontinence episodes and maximum detrusor pressure correlated
      positively with a higher categorization in the nomogram. Therapeutic
      interventions and follow-up controls could be successfully illustrated by the
      nomogram. CONCLUSIONS: The ice water test is a simple tool for unmasking non
      identified detrusor overactivity in neurogenic bladder dysfunction. A severity
      categorization of the detrusor overactivity can be facilitated by the use of the
      ice water test nomogram. After further validation, the ice water test could be
      ultimately used in future as objective assessment for bladder dysfunction.

PMID- 30103279
TI  - Regional variation in the intensity of prostate cancer care: A study of a large
      Medicare sample.

PMID- 30103281
TI  - Regulator of G protein signaling 2 differentially regulates nicotine-induced
      anxiolytic- and antidepressant-like effects in mice.
AB  - This study assessed the role of regulator of G protein signaling 2 (RGS2) in
      nicotine-induced anxiolytic- and antidepressant-like effects using RGS2 wildtype
      (WT) and RGS2 knockout (KO) mice. RGS2 negatively regulates monoaminergic
      neurotransmission, which is implicated in the pathology of anxiety and
      depression. We hypothesized that deletion of RGS2 would enhance nicotine-induced
      anxiolytic- and antidepressant-like effects, which were assessed using the
      elevated plus maze and tail suspension tests, respectively. Anxiolytic-like
      effects were observed in both RGS2 WT and KO mice after administration of low
      dose of nicotine (0.05 mg/kg, base) compared to respective saline controls.
      Additionally, administration of nicotine (0.1 mg/kg, base) compared to saline
      resulted in anxiolytic-like effects in RGS2 KO mice, but not RGS2 WT mice,
      suggesting genetic deletion of RGS2 facilitated anxiolytic-like effects of
      nicotine. Administration of nicotine (0.5 and 1 mg/kg, base) compared to saline
      resulted in antidepressant-like effects in RGS2 WT mice. Antidepressant-like
      effects were observed in RGS2 KO mice only at the highest tested dose of nicotine
      (1 mg/kg, base) compared to saline controls, suggesting that genetic deletion of
      RGS2 decreased sensitivity to antidepressant-like effects of nicotine. Together,
      the data suggest that RGS2 differentially regulated nicotine-induced affective
      behavioral responses. These data suggest that individuals with RGS2 polymorphisms
      may experience differential affective responses to tobacco smoking, which may
      make them vulnerable to developing nicotine addiction.

PMID- 30103282
TI  - Supramolecular chirality transfer in a stereodynamic catalysts.
AB  - We present rhodium catalysts that contain stereodynamic axially chiral biphenol
      derived phosphinite ligands modified with non-stereoselective amides for non
      covalent interactions. A chirality transfer was achieved with (R)- or (S)
      acetylphenylalanine methyl amide, and the interaction mechanism was investigated
      by NMR measurements. These interactions at the non-stereoselective interaction
      sites and the formation of supramolecular complexes result in an enrichment of
      either the (Rax )- or (Sax ) enantiomer of the tropos catalysts, which in turn
      provide the (R)- or (S)-acetylphenylalanine methyl ester in the hydrogenation of
      (Z)-methyl-alpha-acetamidocinnamate.

PMID- 30103280
TI  - Histone Deacetylase Inhibitor Suberanilohydroxamic Acid Treatment Reverses
      Hyposensitivity to gamma-Aminobutyric Acid in the Ventral Tegmental Area During
      Ethanol Withdrawal.
AB  - BACKGROUND: The ventral tegmental area (VTA) is important for alcohol-related
      reward and reinforcement. Mouse VTA neurons are hyposensitive to gamma
      aminobutyric acid (GABA) during ethanol (EtOH) withdrawal, and GABA
      responsiveness is normalized by in vitro treatment with histone deacetylase
      inhibitors (HDACi). The present study examined the effect of a systemically
      administered HDACi, suberanilohydroxamic acid (SAHA) on GABA sensitivity, and
      related molecular changes in VTA neurons during withdrawal after chronic EtOH
      intake in rats. METHODS: Sprague Dawley male adult rats were fed with Lieber
      DeCarli diet (9% EtOH or control diet) for 16 days. Experimental groups included
      control diet-fed and EtOH diet-fed (0- or 24-hour withdrawal) rats treated with
      either SAHA or vehicle injection. Single-unit recordings were used to measure the
      response of VTA neurons to GABA. Immunohistochemistry was performed to examine
      levels of HDAC2, acetylated histone H3 lysine 9 (acH3K9), and GABAA receptor
      alpha1 and alpha5 subunits in the VTA; quantitative polymerase chain reaction was
      performed to examine the mRNA levels of HDAC2 and GABAA receptor subunits.
      RESULTS: VTA neurons from the withdrawal group exhibited GABA hyposensitivity. In
      vivo SAHA treatment 2 hours before sacrifice normalized the sensitivity of VTA
      neurons to GABA. EtOH withdrawal was associated with increased HDAC2 and
      decreased acH3K9 protein levels; SAHA treatment normalized acH3K9 levels.
      Interestingly, no significant change was observed in the mRNA levels of HDAC2.
      The mRNA levels, but not protein levels, of GABAA receptor alpha1 and alpha5
      subunits were increased during withdrawal. CONCLUSIONS: Withdrawal from chronic
      EtOH exposure results in a decrease in GABA-mediated inhibition, and this GABA
      hyposensitivity is normalized by in vivo SAHA treatment. Disruption of signaling
      in the VTA produced by alteration of GABA neurotransmission could be 1
      neuroadaptive physiological process leading to craving and relapse. These results
      suggest that HDACi pharmacotherapy with agents like SAHA might be an effective
      treatment for alcoholism.

PMID- 30103283
TI  - Trophic factors for Parkinson's disease: Where are we and where do we go from
      here?
AB  - Perhaps the most important unmet clinical need in Parkinson's disease (PD) is the
      development of a therapy that can slow or halt disease progression. Extensive
      preclinical research has provided evidence for the neurorestorative properties of
      several growth factors, yet only a few have been evaluated in clinical studies.
      Attempts to achieve neuroprotection by addressing cell-autonomous mechanisms and
      targeting dopaminergic neurons have been disappointing. Four different trophic
      factors have so far entered clinical trials in PD: glial cell line-derived growth
      factor, its close structural and functional analog neurturin, platelet-derived
      growth factor and cerebral dopaminergic neurotrophic factor. This article reviews
      the pre-clinical evidence for the neuroprotective and neurorestorative actions of
      these growth factors and discusses limitations of preclinical models, which may
      hamper successful translation to the clinic. We summarize the previous and
      ongoing clinical trials using growth factors in PD and emphasize the caveats in
      clinical trial design that may prevent the further development and registration
      of potentially neuroprotective and neurorestorative treatments for individuals
      suffering from PD.

PMID- 30103284
TI  - BvCOLD1: A novel aquaporin from sugar beet (Beta vulgaris L.) involved in boron
      homeostasis and abiotic stress.
AB  - Beta vulgaris (sugar beet) is one of the most important industrial crops.
      Screening of a cDNA library for sugar beet genes able to confer cold tolerance
      upon overexpression in yeast identified a novel aquaporin, which we named
      BvCOLD1. The amino acid sequence of BvCOLD1 indicated that an acidic protein (pI
      5.18) is similar to tonoplast intrinsic protein aquaporins. RNA expression
      analysis indicated that BvCOLD1 is expressed in all sugar beet organs. Confocal
      microscopy of a green fluorescent protein-tagged version localized BvCOLD1 in the
      endoplasmic reticulum in yeast and in plant cells. Experiments in yeast showed
      that BvCOLD1 has an important role in transporting several molecules, among them
      is boron, one of the most limiting micronutrients for sugar beet cultivation.
      Transgenic Arabidopsis thaliana plants overexpressing BvCOLD1 showed enhanced
      tolerance to cold, to different abiotic stresses, and to boron deficiency at
      different developmental stages. Searches in databases only retrieved BvCOLD1
      orthologues in genomes from the Chenopodioideae, a subfamily of the Amaranthaceae
      family that includes the closely related crop Spinacea oleracea and halotolerant
      plants such as Salicornia herbacea or Suaeda glauca. Orthologues share a
      conserved sequence in the carboxy terminus, not present in other aquaporins,
      which is required for the functionality of the protein.

PMID- 30103285
TI  - Positron-emission tomography imaging in urological oncology: Current aspects and
      developments.
AB  - Positron-emission tomography/computed tomography combining both functional and
      morphological information has emerged as a powerful tool in oncological imaging
      within the past decades. The most commonly used radiotracer in oncology
      visualizing metabolic information is 2-[18F]fluoro-2-deoxy-d-glucose. However,
      the use of 2-[18F]fluoro-2-deoxy-d-glucose in urological oncology is challenging,
      as it is limited by physiological excretion through the urinary system.
      Therefore, it is only useful when applied to specific indications in selected
      patients with urological malignancy; for example, for detection of residual
      disease in the post-chemotherapy management of patients with seminoma. Despite
      initial promising results in bladder cancer, no relevant additional diagnostic
      value with positron-emission tomography using 2-[18F]fluoro-2-deoxy-d-glucose or
      choline-based tracers could be obtained, and should therefore be used with
      caution or only within clinical trials. In prostate cancer, however, a paradigm
      shift in imaging can be observed after development of new tracers that target the
      prostate-specific membrane antigen. Biochemical recurrent prostate cancer has
      become a clinically widely accepted indication for prostate-specific membrane
      antigen ligand positron-emission tomography/computed tomography, with several
      studies showing superior detection efficacy compared with conventional imaging.
      For primary high-risk prostate cancer, growing evidence suggests well-improved
      staging. The present review aimed to provide an overview of the current status of
      positron-emission tomography imaging in cancer of the urogenital system including
      the latest advances in 68 Ga-labeled and 18 F-labeled positron-emission
      tomography agents targeting the prostate-specific membrane antigen for positron
      emission tomography imaging of prostate cancer.

PMID- 30103286
TI  - Association between dopamine receptor gene polymorphisms and effects of
      risperidone treatment: A systematic review and meta-analysis.
AB  - BACKGROUND: The effect of risperidone treatment in patients with schizophrenia
      varies according to the dopamine receptor genes. This study aimed to evaluate the
      relationship between genes of the dopamine receptors (D1, D2, and D3) and the
      effect of risperidone treatment. METHODS: Three electronic databases (PubMed,
      Embase, and Cochrane Library) were searched for relevant cohort or case-control
      studies published before 9 May 2018. A systematic review and meta-analysis was
      performed for qualitative and quantitative assessment of the relationship between
      the dopamine receptors D1, D2, and D3 (DRD1, 2, and 3) and the effect of
      risperidone treatment. The summary odds ratio (OR) and weighted mean difference
      (WMD) in a random-effects model were used to measure these relationships.
      RESULTS: Twelve studies involving 24 SNPs were included. DRD2 (Ser311Cys,
      rs1801028 Ser/Ser) significantly lowered the improvement rate (determined by the
      PANSS score) unlike Ser/Cys (WMD: -11.58, 95% CI: -17.35 to -5.18). For Asian
      patients, A241G (rs1799978) AA carriers showed greater improvement after
      risperidone therapy (P < 0.05). The polymorphisms of 141C Ins/Del (rs1799732),
      T939C (rs6275), rs6277, and TaqID (rs1800498) may also influence the treatment
      effect. TaqIA (rs1800497) and TaqIB (rs17294542) were not associated with the
      rate of response to risperidone. DRD3 was not associated with an improvement in
      the PANSS total score; however, Ser9Gly might be related to a change in negative
      symptoms. No significant effect of DRD1 (rs5326, rs4867798, rs4532, and
      rs11749676) was found. CONCLUSIONS: Our result supported the hypothesis that DRD2
      affected risperidone treatment. DRD1 had no significant effect on the response to
      risperidone, whereas DRD3 might be associated with an improvement in negative
      symptoms. Larger observational studies are warranted to verify these findings and
      identify other genetic factors involved.

PMID- 30103287
TI  - How Will Alcohol Research be Impacted by Future Reduction in Nicotine Content in
      Cigarettes?

PMID- 30103288
TI  - Designing an ultra-short antibacterial peptide with potent activity against
      Mupirocin-resistant MRSA.
AB  - Staphylococcus aureus is the pathogen responsible for the majority of human skin
      infections. In particular, the methicillin-resistant variety, MRSA, has become a
      global clinical concern. The extensive use of mupirocin, the first-line topical
      antibacterial drug of choice, has led to the emergence of mupirocin-resistant
      MRSA globally, resulting in the urgent need for a replacement. Antimicrobial
      peptides are deemed plausible candidates. Herein, we describe a structure
      activity relationship approach in the design of an ultra-short peptide with
      potent anti-MRSA activity with a rapid, bactericidal mode of action. Coupled to a
      low cytotoxic activity, we believe our lead compound can be developed into a
      topical antibacterial agent to replace mupirocin as the first-line drug for
      treating MRSA skin infections.

PMID- 30103289
TI  - Paternal line effects of early experiences persist across three generations in
      rhesus macaques.
AB  - The effects of early stress may not be limited to the exposed generation, but are
      sometimes passed on to subsequent generations. Such non-genetic transgenerational
      inheritance is a potentially important developmental and evolutionary force. We
      compared the transgenerational effects of maternal and paternal line early stress
      on anxiety- and health-related traits in three non-exposed generations (F1, F2
      and F3) of semi-naturalistically raised rhesus macaques. As infants, F0 macaques
      were exposed to nursery rearing (NR) or semi-naturalistic social conditions
      (CONTROL). Three hundred forty non-exposed F1-F3 descendants were CONTROL reared
      and physiological and behavioral measures were collected during standardized
      assessment at 3-4 months of age. Paternal line NR was significantly associated
      with greater nervousness in F1-F3 and lower immune cell counts in F1-F2. Maternal
      line NR effects were not observed. This study suggests that acquired stress
      related traits may be "inherited" across generations in primates, through complex
      social or germ-line mechanisms.

PMID- 30103290
TI  - Physical abuse of the elderly: a 4-year retrospective evaluation in the emergency
      department.
AB  - AIM: Elderly physical abuse (EPA) is defined as injury or assault to or the
      restriction of an elderly person. Although EPA is an important social problem,
      its diagnosis is difficult because of tendency to cover up the event. In this
      study, patients aged 65 years and over who presented at the emergency department
      (ED) for forensic reasons and in whom physical abuse was suspected were examined.
      The aim of this study was to raise ED awareness of EPA and thereby to contribute
      to treatment plans for these patients in the ED. METHODS: The study was conducted
      over a 4-year period between January 2013 and January 2017. Patients were
      selected retrospectively from the hospital information system according to the
      following criteria: (i) admission to ED with trauma; (ii) aged 65 and older; and
      (iii) evaluated as having forensic trauma by an ED specialist based on either the
      patient's history or the specialist's observations and suspicions. RESULTS: The
      patients included 80 men (69%) and 36 women (31%), with a mean age of 73.92 +/-
      7.08 years. The length of ED stay was 0-1 h in 27.6% of patients and 1-6 h in
      46.6%. When the causes of physical trauma were examined, general assault was seen
      as the most prevalent, occurring in nearly 63% of the patients. CONCLUSIONS:
      There may be three conclusions for the current study: First, although EPA is a
      rare problem for patients referred to emergency services, health professionals
      should be suspicious when examining patients 65 years or older because of the
      difficulties of diagnosing EPA. Second, in patients with no history of suspicious
      trauma or suspicious radiological imaging results, EPA is also common. Third,
      because of the undetected EPA mechanism, patients should be examined forensically
      in suspicious cases and deaths.

PMID- 30103291
TI  - Editorial Comment to Assessing perioperative, functional and oncological outcomes
      of patients with imperative versus elective indications for robot-assisted
      partial nephrectomy: Results from a high-volume center.

PMID- 30103292
TI  - Are language features and emotion regulation related to maternal depression in
      autism and language delay?
AB  - BACKGROUND: Language and communication are very important in child social,
      emotional and cognitive development. Delay in language is usually the first
      complaint for children diagnosed with autism spectrum disorder (ASD) or
      developmental language delay (DLD). This study evaluated language features and
      emotion regulation skills in children diagnosed with ASD and DLD and their
      association with maternal depression. METHOD: The sample consisted of children
      aged 24-54 months diagnosed with ASD (n = 31), or with DLD (n = 45), and 52
      healthy controls. The Test of Early Language Development (TELD-3) was used to
      evaluate language profiles, and the beck depression inventory (BDI) was used to
      examine maternal depression. Children's emotion regulation skills were evaluated
      using the emotion regulation checklist. RESULTS: Children with DLD had a
      significantly higher developmental age, were linguistically more developed and
      had better emotion regulation than the ASD group. All domains of language on TELD
      3 except expressive syntax were more developed in DLD. Maternal BDI score did not
      differ significantly between DLD and ASD. Both of these disorders were not
      associated with maternal depression. CONCLUSION: Children with DLD were less
      impaired than children with ASD, both in terms of language and in emotion
      regulation.

PMID- 30103293
TI  - Visual prognosis in seronegative idiopathic optic neuritis finally elucidated: as
      bad as that in anti-AQP4 antibody-positive optic neuritis.

PMID- 30103294
TI  - Steric Demand and Rate-determining Step for Photoenolization of Di-ortho
      substituted Acetophenone Derivatives.
AB  - Laser flash photolysis of ketone 1 in argon-saturated methanol yields triplet
      biradical 1BR (tau = 63 ns) that intersystem crosses to form photoenols Z-1P
      (lambdamax = 350 nm, tau ~ 10 MUs) and E-1P (lambdamax = 350 nm, tau > 6 ms). The
      activation barrier for Z-1P re-forming ketone 1 through a 1,5-H shift was
      determined as 7.7 +/- 0.3 kcal mol-1 . In contrast, for ketone 2, which has a
      less sterically hindered carbonyl moiety, laser flash photolysis in argon
      saturated methanol revealed the formation of biradical 2BR (lambdamax = 330 nm,
      tau ~ 303 ns) that intersystem crosses to form photoenol E-2P (lambdamax = 350
      nm, tau > 42 MUs), but photoenol Z-2P was not detected. However, in more viscous
      basic H-bond acceptor (BHA) solvent, such as hexamethylphosphoramide, triplet 2BR
      intersystem crosses to form both Z-2P (lambdamax = 370 nm, tau ~ 1.5 MUs) and E
      2P. Thus, laser flash photolysis of ketone 2 in methanol reveals that intersystem
      crossing from 2BR to form Z-2P is slower than the 1,5-H shift of Z-2P, whereas in
      viscous BHA solvents, the 1,5-H shift becomes slower than the intersystem
      crossing from 2BR to Z-2P. Density functional theory and coupled cluster
      calculations were performed to support the reaction mechanisms for
      photoenolization of ketones 1 and 2.

PMID- 30103295
TI  - Modification of erythropoietin structure by N-homocysteinylation affects its
      antiapoptotic and proliferative functions.
AB  - Many patients under therapy with recombinant human erythropoietin (rhuEPO) show
      resistance to the treatment, an effect likely associated with the accumulation of
      tissue factors, especially in renal and cardiovascular diseases.
      Hyperhomocysteinemia due to high serum levels of homocysteine has been suggested
      among the risk factors in those pathologies. Its main effect is the N
      homocysteinylation of proteins due to the interaction between the highly reactive
      homocysteine thiolactone (HTL) and lysine residues. The aim of this study was to
      evaluate the effect of N-homocysteinylation on the erythropoietic and
      antiapoptotic abilities of EPO, which can be a consequence of structural changes
      in the modified protein. We found that both cellular functions were altered in
      the presence of HTL-EPO. A decreased net positive charge of HTL-EPO was detected
      by capillary zone electrophoresis, while analysis of polyacrylamide gel
      electropherograms suggested formation of aggregates. Far-UV spectra, obtained by
      Circular Dichroism Spectroscopy, indicated a switch of the protein's secondary
      structure from alpha-helix to beta-sheet structures. Results of Congo red and
      Thioflavin T assays confirm the formation of repetitive beta-sheet structures,
      which may account for aggregates. Accordingly, Dynamic Light Scattering analysis
      showed a markedly larger radius of the HTL-EPO structures, supporting the
      formation of soluble oligomers. These structural changes might interfere with the
      conformational adaptations necessary for efficient ligand-receptor interaction,
      thus affecting the proliferative and antiapoptotic functions of EPO. The present
      findings may contribute to explain the resistance exhibited by patients with
      cardio-renal syndrome to treatment with rhuEPO, as a consequence of structural
      modifications due to protein N-homocysteinylation.

PMID- 30103296
TI  - Blue Laser Imaging with a Small-Caliber Endoscope Facilitates Detection of Early
      Gastric Cancer.
AB  - Conventional endoscopy often misses early gastric cancers with minimal red
      discoloration because they cannot be distinguished from inflamed mucosa. We
      treated a patient with a small early gastric cancer that was difficult to
      diagnose using conventional endoscopy. Conventional endoscopy using a small
      caliber endoscope showed only subtle red discoloration of the gastric mucosa.
      However, blue laser imaging showed a clearly discolored area measuring 10 mm in
      diameter around the red lesion, which was distinct from the surrounding inflamed
      mucosa. Irregular vessels on the tumor surface (suspicious for early gastric
      cancer) were observed even with small-caliber endoscopy. Biopsy revealed a well
      moderately differentiated tubular adenocarcinoma, and endoscopic submucosal
      dissection was performed. Histopathological examination of the specimen confirmed
      well-moderately differentiated adenocarcinoma localized to the mucosa with slight
      depression compared to the surrounding mucosa, consistent with the endoscopic
      findings. This small early gastric cancer became clearly visible with blue laser
      imaging using small-caliber endoscopy.

PMID- 30103297
TI  - DOMINATE Wounds.
AB  - Chronic wounds are a significant health problem worldwide. Often they are
      initially managed with various focal treatments until a specialist becomes
      involved, sometimes weeks or months after treatment has begun. Even at the
      specialist level, practices and guidelines are inconsistent due to a lack of high
      level evidence. A disease management system for chronic wounds that is simple,
      practical, and adoptable by a variety of wound care practitioners is needed. Such
      a system would guide wound care providers to address the critical aspects of
      wound care in a prioritized, systematic sequence, leading to faster healing of
      simple wounds, and timely advancement to more complex therapies for wounds that
      require such treatment. This paper describes an empirically developed wound care
      management system that has been successfully implemented and provides evidence
      based rationale for each of its components. Relatively simple and practical, this
      system organizes an approach to any type of wound, routine or complex.

PMID- 30103299
TI  - Deep heating therapy via MF radiowaves versus superficial heating therapy in the
      treatment of nonspecific chronic low back pain: A double blind randomized trial.
AB  - BACKGROUND: Nonspecific Chronic Low Back Pain (CLBP) is a condition difficult to
      treat due to multiple etiopathogenesis and there is wide consensus on the
      multidisciplinary approach. In physiotherapy, the Medium Frequencies (MF)
      diathermy has recently been introduced but without enough evidence of
      effectiveness. OBJECTIVE: To explore the effects of a deep heating therapy (DHT)
      produced by a MF diathermy for the treatment of CLBP compared with a superficial
      heating therapy (SHT). The study was a double blind randomized trial. METHODS:
      Forty-nine patients affected by CLBP were randomly subdivided in 2 groups and
      treated with either DHT (450 KHz) or SHT via electric resistance applying the
      same instrument on the lumbar spine. NRS (Numerical Rating Scale) for pain and
      ODI (Oswestry Disability Index) for disability were used as outcome measures. The
      follow up was: T1, 15 days (end of the therapy); T2, 30 days; T3, 45 days after
      T0. RESULTS: Both therapies were effective in reducing pain throughout the follow
      up with greater improvement in DHT group at T1. DHT resulted to have a higher
      efficacy with respect to SHT in reducing disability (ODI) throughout all follow
      ups. CONCLUSION: This study provides evidence of the positive effects of MF radio
      waves diathermy in the treatment of CLBP.

PMID- 30103298
TI  - Trunk muscle endurance in Chinese adults.
AB  - BACKGROUND: Previous studies in non-Chinese populations have found a relationship
      between performance on isometric trunk muscle endurance tests and low back pain
      (LBP). However, the relationship between trunk muscle endurance and LBP in
      Chinese populations has received little attention and age-referenced data have
      not been reported. OBJECTIVE: Evaluate the relationship between age-referenced
      isometric trunk muscle endurance values and LBP in a Chinese cohort. METHODS: One
      hundred and eighty-eight participants (20-59-years) performed four timed
      endurance tests (Biering-Sorensen, plank, left/right side bridge) in random
      order. Participants with a history of LBP completed an Oswestry Disability Index
      (ODI) and pain scale. Holding-times for the four tests were summed and receiver
      operating characteristic (ROC) curve analysis was performed to differentiate
      participants with and without LBP. RESULTS: Data were grouped by age. Analysis
      revealed similar endurance values to those reported in non-Chinese populations,
      except longer holding times were recorded in the 50-59 yr Chinese cohort. Pain
      scores were positively correlated with ODI scores. ROC curve analysis showed that
      the area under the curve was 0.723 and optimal cut-off was 288 sec (sensitivity
      and specificity both 0.75). CONCLUSIONS: This study is the first to describe
      trunk muscle endurance reference data in Chinese people. Individuals with a
      summed endurance time of < 288 seconds appear more likely to suffer LBP.

PMID- 30103300
TI  - Does clinically measured ankle plantar flexor muscle strength or weakness
      correlate with walking performance in healthy individuals?
AB  - : Muscle strength is usually measured using isometric hand-held dynamometers
      (HHDs) in the clinic. However, during functional activities, the muscle acts more
      dynamically. The aim of this study was to investigate the relation between
      clinically measured plantar flexor (PF) muscle strength (PFMS) and laboratory
      measurements of peak ankle plantar flexion power generation (APFPG), peak ankle
      moment (PAM), peak plantar flexion velocity (PFV) and mean gait velocity in
      healthy participants. METHODS: The maximum PFMS on non-dominant sides in 18 able
      bodied persons 23.88 (SD 3.55 years) was measured before (Pre-S) and after a
      stretching (Post-S) procedure (135 sec. * 13 rep. with 5 sec. rest) using a HHD.
      The stretching procedure was used to generate temporary PF muscle weakness. Gait
      analysis was carried out for Pre-S and Post-S conditions. Normalized (by weight
      and height) and non-normalized HHD scores and differences for both conditions
      were correlated by Pearson correlation coefficient calculations (p< 0.05).
      RESULTS: Reduced PFMS (%23, p< 0.001) in Post-S, according to the HHD scores, has
      only a weak correlation with APFPG (r> 0.3, p< 0.5). Gait velocity was found to
      be strongly correlated with APFPG only in the Post-S condition (r= 0.68, p<
      0.002). HHD scores and PAM were moderately correlated with the non-normalized
      Post-S condition (r= 0.44, p= 0.70) and strongly correlated with the non
      normalized Pre-S condition (r= 0.62, p< 0.01). DISCUSSION: HHD scores of plantar
      flexor muscles give very limited information about the PF performance during
      walking in healthy individuals. Simple normalization did not improve the
      relations. Clinically measured isometric muscle strength and muscle weakness have
      only moderate strengths for establishing a treatment protocol and for predicting
      performance during walking in neurologically intact individuals.

PMID- 30103302
TI  - Diagnostic value of serum PIVKA-II levels for BCLC early hepatocellular carcinoma
      and correlation with HBV DNA.
AB  - BACKGROUND: It is reported that prothrombin induced by vitamin K absence-II
      (PIVKA-II) has a better performance of diagnosis for HCC, and has also been known
      to be an independent risk factor for vascular invasion. Few studies study the
      relationship between PIVKA-II and HBV DNA. OBJECTIVE: To determine the clinical
      value of serum Prothrombin induced by vitamin K absence-II (PIVKA-II) in early
      hepatocellular carcinoma (HCC), and to explore its relationship with vascular
      invasion and HBV DNA. METHODS: In a Chinese cohort, we conducted a case-control
      study to compare the performances of a-fetoprotein (AFP) and PIVKA-II serum
      levels for diagnosis of HCC and early HCC. Fifty one healthy controls, 37 chronic
      hepatitis patients, 43 cirrhotic patients and 143 HCC cases of which 48 (33.57%)
      had early stage HCC (n= 19 very early, n= 29 early) were enrolled. We explored
      the correlation between PIVKA-II serum level and several pathological features
      such as vascular invasion. The serum levels of and AFP were measured by
      chemiluminescence assay (CLIA) and electrochemiluminescence assay (ECLA).
      RESULTS: The serum levels of both PIVKA-II and AFP in HCC group were higher than
      that in chronic hepatitis, cirrhosis and healthy control groups. The sensitivity,
      specificity, positive predictive value, negative predictive value and kappa of
      PIVKA-II were higher than AFP in the diagnosis of HCC. Serum PIVKA-II level was
      correlated with tumor size, tumor cell differentiation and BCLC staging (P<
      0.05). For the diagnosis of early HCC, the combination of PIVKA-II (AUC 0.812;
      95% CI, 0.702-0.894) and AFP (0.797; 95% CI, 0.686-0.883) slightly improve the
      diagnostic performance for early HCC(AUC 0.849; 95% CI, 0.745-0.923). PIVKA-II >
      166 mAU/ml is an independent risk factor for vascular invasion. The serum HBV DNA
      level in cirrhosis and HCC patients was significantly higher than in chronic
      hepatitis patients. We detected a negative association between serum PIVKA-II and
      serum HBV DNA levels. CONCLUSIONS: PIVKA-II was more efficient than AFP for the
      diagnosis of early HCC and has no correlation with serum HBV DNA levels.

PMID- 30103301
TI  - lncRNA GHET1 down-regulation suppresses the cell activities of glioma.
AB  - Long noncoding RNAs (lncRNAs) are emerging as new modulators in cancer
      origination and progression. The previous study found lncRNA gastric carcinoma
      highly expressed transcript 1 (GHET1) was significantly up-regulation in the
      gastric cancer. In our present study, we studied the GHET1 expression in glioma
      and its effects to biological activities of glioma in vitro and vivo studies. In
      the clinical analysis, the results were shown that lncRNA GHET1 was significantly
      up-regulation and the Numb protein expression was significantly down-regulation
      in glioma tissues. In vitro and vivo studies, the results were shown that lncRNA
      GHET1 knock-down had effects to inhibit biological activities by regulation Numb
      and down-stream genes P53 and MMP2/9. The results suggested that GHET1 is a novel
      tumor oncogene by Numb in glioma. LncRNA GHET1 may serve as a potential biomarker
      and therapeutic target for glioma.

PMID- 30103303
TI  - Taurine, glutamic acid and ethylmalonic acid as important metabolites for
      detecting human breast cancer based on the targeted metabolomics.
AB  - BACKGROUND: This study investigated the use of serum amino acids and organic
      acids profiles as the novel metabolites for screening breast cancer (BC)
      patients. METHODS: A total of 116 subjects as training set were divided into the
      following three groups: BC patients (n= 34), benign (BE) patients (n= 38) and
      controls (n= 44). The amino acids profiles from three groups were measured using
      liquid chromatography-mass spectrometry and organic acids profiles in three
      groups were studied by gas chromatography-mass spectrometry. The resultant study
      data set was subjected to multivariate statistical analysis to identify important
      metabolites related with BC and construct the criteria for discriminating BC
      patients from BE subjects or controls. A test data set derived from 60 patients
      (30 BC and 30 BE subjects) and 30 controls was used to validate the stability of
      the different metabolites. RESULTS: The serum amino acids and organic acids
      profiles significantly differed between the BC patients, BE patients and the
      controls. Our results demonstrate that combinations of three candidate
      metabolites from taurine, glutamic acid and ethylmalonic acid were found to
      mirror tumour burden, with AUC values ranging from 0.751 to 0.834 when comparing
      BC patients to the controls. The areas under the curve from the taurine, glutamic
      acid and ethylmalonic acid in validated study were 0.901, 0.924 and 0.749,
      respectively. CONCLUSIONS: This study shows that amino acids and organic acids
      profiles will be a potential screening tool for BC patients. The dysregulated
      metabolism of amino acids and organic acids in breast cancer might be useful for
      the diagnosis, therapy, prognosis and understanding the pathogenesis of breast
      cancer.

PMID- 30103304
TI  - miR-486 inhibited osteosarcoma cells invasion and epithelial-mesenchymal
      transition by targeting PIM1.
AB  - OBJECTIVE: Osteosarcoma is the most common malignant tumor of bone with high
      recurrent rate. miR-486 was downregulated and acted as a tumor suppressor in
      plenty of tumors. The purpose of this study was to explore how miR-486 worked in
      osteosarcoma on cell invasion and EMT. RESULTS: miR-486 was low expressed in
      osteosarcoma while PIM1 was overexpressed, and it had negative correlation
      between miR-486 and PIM1. miR-486 upregulation or PIM1 downregulation could
      inhibit osteosarcoma cell invasion and EMT. Meanwhile, miR-486 mediated PIM1
      expression through binding to PIM1 mRNA 3'-UTR. PIM1 could reveal partial
      function of miR-486 on osteosarcoma invasion. In addition, miR-486 low expression
      or PIM1 overexpression predicted poor prognosis of osteosarcoma patients.
      CONCLUSION: miR-486 regulated osteosarcoma cell invasion and EMT through
      targeting to PIM1. miR-486 low expression or PIM1 overexpression predicted poor
      prognosis of osteosarcoma patients. The newly identified miR-486/PIM1 axis
      provides novel insight into the pathogenesis of osteosarcoma.

PMID- 30103305
TI  - Feasibility, safety and effectiveness in measuring microvascular resistance with
      regadenoson invasive coronary flow assessment with regadenoson.
AB  - AIMThe study aims to test whether simultaneous measurement of fractional flow
      reserve (FFR), coronary flow reserve (CFR) and index of microcirculatory
      resistance (IMR) is feasible, safe and effective during regadenoson-induced
      hyperemia.METHODS AND RESULTSFFR, CFR and IMR were measured simultaneously during
      regadenoson (Rapiscan 400MUg) -induced hyperemia in 50 patients with stable
      coronary artery disease with a SYNTAX score of <22. Simultaneous measurement of
      FFR, CFR and IMR was technically feasible in all cases (50/50). No side effects
      occurred and even patients fulfilling classical contraindications for the use of
      adenosine (10/50) could be included. Regadenoson-induced hyperemia remained
      stable after maximal pressure drop for more than 35 sec as measured by systemic
      aortic and distal coronary pressure. There was a significant drop in transit mean
      time from baseline to hyperemia of more than 50% (1.0 +/- 0.6 s vs. 0.4 +/- 0.2
      s, p <  0.01). Patients' mean IMR value was 23.4, and IMR values above 75th
      percentile significantly correlated with metformin demanding diabetes mellitus
      with OR 21.76 and nicotine abuse with OR 10.28.CONCLUSIONA single intravenous
      regadenoson bolus via peripheral line increases coronary blood flow without
      harmful systemic side effects enabling interventionists to simultaneously assess
      FFR, CFR and IMR in patients with stable coronary artery disease.

PMID- 30103306
TI  - The prognostic value of red blood cell characteristics on diabetic retinopathy
      development and progression in type 2 diabetes mellitus.
AB  - BACKGROUNDAlthough it is considered that the pathogenesis of diabetic retinopathy
      (DR) in type 2 diabetes mellitus (T2DM) is primarily due to chronic hyperglycemia
      resulting in vascular changes and retinal ischemia, the red blood cells (RBCs)
      disorders might also represent an important pathophysiological risk
      factor.OBJECTIVETo evaluate whether the RBC properties contribute to DR
      development and progression in T2DM.METHODSThis prospective observational study
      comprised 247 persons with T2DM free of DR or with non proliferative DR without
      any signs of anaemia. The patients were reacessed after 60-months.RESULTSThe mean
      age of our study population was 56 years, 54.9% males with diabetes duration of
      11,18+/-1,28 years. During the follow up, 16 (5.84% ) participants developed non
      proliferative DR and 9 (3.64% ) progressed to PDR while the mean corpuscular
      volume (MCV) and red cell distribution width (RDW) MCV rose. Both MCV and RDW
      correlated positively with HbA1c (r = 0,468, p = 0.003 and r = 0.521, p < 
      0.001), while Cox regression analysis revealed that besides age, diabetes
      duration, HbA1c, hypertension and dyslipidemia presence, MCV and RDW are also
      associated with the risk of DR development and progression (HR 1.057 and 1.237, p
      <  0.001).CONCLUSIONSWe clearly demonstrated that RBC's characteristics might
      represent a risk factor for DR development and progression.

PMID- 30103307
TI  - Savitzky-Golay filter based contrast-enhanced ultrasound quantification in
      hepatic tumors: Methodology and its correlation with tumor angiogenesis.
AB  - BACKGROUND: Savitzky-Golay filter is a digital filter used in data smoothing, we
      introduced a contrast-enhanced ultrasound (CEUS) quantification software based on
      the filter (SGCQ). OBJECTIVE: To explore the methodology of analyzing hepatic
      tumors hemodynamics applying SGCQ software and the correlation between SGCQ
      parameters and hepatocellular carcinoma (HCC) angiogenesis. METHODS: Nighty-seven
      right-lobe located hepatic mass cases (15 females and 82 males, mean age 58+/
      10y, mean lesion size: 39.9+/-11.6 mm) underwent CEUS scan preoperatively and had
      a final diagnosis of HCC (n = 52) or colorectal cancer metastatic liver tumors
      (MLT, n = 45) were included. CEUS was carried out using a 1-5 MHz convex probe.
      The CEUS clips were recorded and analyzed off-line to obtain the parameters. The
      parameters were analyzed by 3 observers separately to investigate inter-observer
      variability. Parameters were compared between tumor and adjacent liver and
      between different tumors. Immunohistochemistry was used to evaluate the
      microvessel density (MVD) of HCC, and the correlation between the parameters and
      MVD was analyzed. RESULTS: Intraclass correlation coefficient (ICC) of all
      parameters were greater than 0.75 except wash-in slope (a3) and time to peak
      (TTP) of adjacent liver. The parameters of a3, wash-out slope (a2), perfusion
      time (PT) and area under the curve (AUC) were significantly different between HCC
      and liver. The a2, a3, AUC, PT and enhanced intensity (EI) were significantly
      different between MLT and liver. AUC, a2, a3, da1 and dPI were significantly
      different between HCC and MLT. AUC, a2 and EI correlated with MVD. CONCLUSION:
      SGCQ software quantification have good consistency among three observers, the
      parameters of SGCQ can display the hemodynamics of HCC and MLT and the difference
      between them. AUC and EI can serve as useful biomarkers in tumor angiogenesis
      evaluation.

PMID- 30103308
TI  - Antibodies prevalence against Haemophilus influenzae type b in Jeddah population,
      Saudi Arabia. II. Antibodies subclasses.
AB  - Our previous reported that Jeddah, Saudi Arabia population have a comparable and
      protective herd immunity represented by IgG, IgA and IgM against Haemophilus
      influenzae type b (Hib), by using indirect ELISA test was used to evaluate
      Haemophilus influenzae type b (Hib) anti-polyribosyl-ribitol phosphate (PRP)
      total antibodies (IgM, IgG, IgA) in 1,003 sera samples. Current report was
      evaluated the IgG and IgA subclasses responsible about this protection using same
      methodology. IgG, IgA, and their subclasses are responsible about this
      circulating protection. Our study will consider the first report evaluate the
      levels of IgA subclasses and its relation to ages, as well as the relations
      between anti-Hib antibody subclass and age. The current results demonstrated that
      the highest levels concentrated in IgG1 and IgG2, while IgG3 and IgG4 showed the
      lowest levels. So, their concentrations were arranged in IgG1 > IgG2 > IgG3 >
      IgG4. The results indicated that the age and gender have no effect on both IgG or
      IgA subclasses in healthy immunized individuals enrolled. While, IgA1
      concentrations were significantly higher than IgA2 in all age categories
      regardless of gender. It seem that the IgG1, IgG2 and IgA1 subclasses were the
      main constituent of Jeddah herd immunity against Hib. Finally, to the best of our
      knowledge, there were no previous reports that focusing on the levels of IgA
      subclasses and its relation to ages, so our study considers the first worldwide.

PMID- 30103309
TI  - Serum cytokine profile in schizophrenic patients.
AB  - Schizophrenia is a chronic severe mental disorder in which immunologic imbalances
      have been reported. Some researchers have demonstrated dysregulation of cytokine
      levels in this mental disorder. Considering the possible role of cytokines in the
      pathogenesis or clinical course of schizophrenia, we assessed serum levels of IL
      4, IL-10, IL-17A and IFN-gamma in a homogenous sample of Iranian patients who
      were in remission under treatment with Clozapine compared with sex and age
      matched controls. There was a statistically significant difference in IL-4 levels
      between patients and healthy subjects (P= 0.023). IL-4 levels were 83% higher in
      cases than in control group. No significant group*gender interaction was detected
      suggesting the similar IL-4 levels between males and females in each study group.
      There was no statistically significant difference in IFN-gamma levels between
      patients and healthy subjects, but IFN-gamma levels were 70% higher in male
      compared with female group. No significant differences have been found in serum
      levels of other cytokines between cases and controls or between males and
      females. The higher levels of IL-4 in patients treated with Clozapine might be
      due to effects of this antipsychotic drug on immune responses. Future studies are
      needed to elaborate the exact underlying mechanism.

PMID- 30103310
TI  - Antibodies prevalence against Haemophilus influenzae type b in Jeddah population,
      Saudi Arabia. III. Antibodies avidity.
AB  - Our previous results showed higher level of anti-Hib IgG (2.41 MUg/ml) average
      geometric mean concentration (GMC) regardless of age and gender, followed by
      levels of IgM (0.91 MUg/ml) and IgA (0.34 MUg/ml), reflecting the prevalence of
      immunity against Hib. Current study was evaluated the avidity profile for these
      high anti-Hib concentration. The IgM avidity analysis did not revealed any
      significant results between male and female values. While, the average of IgA
      avidity in male samples were significantly (P< 0.05) higher than the average of
      female. Also, The result showed that high percentage of population has moderate
      to high IgG avidity. The study showed lower avidity percentages of both IgM and
      IgA comparing to IgG. More studies are suggested to be done on individuals with
      low avidity considering the secondary immunodeficiency in participant's history.

PMID- 30103311
TI  - Detection of Toxoplasma gondii B1 gene in placenta does not prove congenital
      toxoplasmosis.
AB  - BACKGROUND: Congenital toxoplasmosis is an important disease that occurs when
      pregnant women become infected with Toxoplasma gondii during pregnancy. The aim
      of this study was to investigate the presence of T. gondii B1 gene in placental
      tissues of IgM seronegative women. MATERIALS AND METHODS: In this research,
      chronic toxoplasmosis was identified through examination of blood samples in a
      group of pregnant women by anti-Toxoplasma IgG and IgM ELISA and nested-PCR
      techniques. IgG avidity test was used to estimate the onset of infection in some
      pregnant women with chronic infection. After delivery, some umbilical cord and
      neonatal blood were tested by anti-Toxoplasma IgM ELISA, and also the B1 gene of
      T. gondii was investigated in their placental tissue by nested-PCR. Some factors
      such as blood sampling time and some clinical symptoms experienced during
      pregnancy were recorded. RESULTS: One hundred and sixty seven out of 653 (25.6%)
      pregnant women were positive for anti-Toxoplasma IgG. Of them, 165 (98.8%) were
      negative for anti-T. gondii IgM. Six out of 10 (60%) placental tissues from IgG
      seropositive, IgM seronegative women were positive for T. gondii B1 gene, while
      anti-Toxoplasma IgM was negative in the umbilical cord and neonatal blood
      samples. The results of IgG avidity test showed low avidity in one and high
      avidity in two women's samples. The B1 gene was not found in the blood samples of
      any of the six mothers. The most symptoms experienced during pregnancy were
      headache and nausea. CONCLUSION: The detection of B1 gene in placental tissues of
      the healthy newborn infants reiterates that presence of T. gondii in the placenta
      does not always result in congenital toxoplasmosis.

PMID- 30103312
TI  - Nomenclature of humanized mAbs: Early concepts, current challenges and future
      perspectives.
AB  - Nomenclature of monoclonal antibodies traditionally followed a strict scheme
      indicating target and species information. Because of the rapid advances in this
      field, emphasized by approval of four humanized and six human antibodies in 2017,
      the International Nonproprietary Name of new antibodies was updated profoundly by
      removing the species substem completely. In this review we give an overview about
      what developments led to the preference of the scientific community towards human
      like antibodies. We summarize the major updates in naming schemes that tried to
      classify antibodies according to their humanization technique or to the final
      primary sequence and how this led to the erroneous perception to indicate
      expected immunogenicity. Following the new 2017 nomenclature update, there will
      not be any information available about the species origin in the names of new
      antibodies, which emphasizes the need for providing additional supplemental
      information to the scientific community and develop tools to accurately estimate
      and control the safety of new monoclonal antibody molecules.

PMID- 30103314
TI  - Connected Speech Features from Picture Description in Alzheimer's Disease: A
      Systematic Review.
AB  - The language changes that occur over the course of Alzheimer's disease (AD) can
      impact communication abilities and have profound functional consequences. Picture
      description tasks can be used to approximate everyday communication abilities of
      AD patients. As various methods and variables have been studied over the years,
      current knowledge about the most affected features of AD discourse in the context
      of picture descriptions is difficult to summarize. This systematic review aims to
      provide researchers with an overview of the most common areas of impairment in AD
      discourse as they appear in picture description tasks. Based on the 44 articles
      fulfilling inclusion criteria, our findings reflect a multidimensional pattern of
      changes in the production (speech rate), syntactic (length of utterance), lexical
      (word-frequency and use of pronouns), fluency (repetitions and word-finding
      difficulties), semantic (information units), and discourse (efficiency) domains.
      We discuss our findings in the light of current research and point to potential
      scientific and clinical uses of picture description tasks in the context of AD.

PMID- 30103313
TI  - Depressive Symptoms Are Associated with Cognitive Function in the Elderly with
      Type 2 Diabetes.
AB  - BACKGROUND: Type 2 diabetes (T2D) is a metabolic condition associated with poor
      clinical and cognitive outcomes including vascular disease, depressive symptoms,
      cognitive impairment, and dementia. In the general elderly population, depression
      has been consistently identified as a risk factor for cognitive
      impairment/decline. However, the association between depression and cognitive
      function in T2D has been understudied. OBJECTIVE: We investigated the association
      between depression and cognitive function in a large sample of cognitively normal
      elderly with T2D. METHODS: In this cross-sectional study, we examined 738
      participants, aged 65-88 years old, enrolled in the Israel Diabetes and Cognitive
      Decline study. For each cognitive domain (Episodic Memory, Executive Function,
      Attention/Working Memory, Language/Semantic Categorization) and Overall
      Cognition, multiple linear regressions assessed its association with depression
      (score greater than 5 on the 15-item version of the Geriatric Depression Scale
      [GDS]), adjusting for age, sex, and education. RESULTS: Depression (n = 66, 8.9%)
      was associated with worse performance on tasks of Executive Function (p = 0.004),
      Language/Semantic Categorization (p < 0.001), and Overall Cognition (p < 0.002),
      but not Episodic Memory (p = 0.643) or Attention/Working Memory (p = 0.488).
      Secondary analyses using GDS as a continuous variable did not substantially
      change the results. Adjusting also for a history of antidepressant medication use
      slightly weakened the findings. CONCLUSION: Significant associations of
      depression with several cognitive domains and Overall Cognition even in
      cognitively normal elderly with T2D, suggest that depression may have a role in
      impaired cognitive function in T2D, which may be attenuated by antidepressants.

PMID- 30103316
TI  - Prominent Non-Memory Deficits in Alzheimer's Disease Are Associated with Faster
      Disease Progression.
AB  - BACKGROUND: Alzheimer's disease (AD) is a heterogeneous disorder. OBJECTIVE: To
      investigate whether cognitive AD subtypes are associated with different rates of
      disease progression. METHODS: We included 1,066 probable AD patients from the
      Amsterdam Dementia Cohort (n = 290), Alzheimer's Disease Neuroimaging Initiative
      (n = 268), Dementia Competence Network (n = 226), and University of California,
      San Francisco (n = 282) with available follow-up data. Patients were previously
      clustered into two subtypes based on their neuropsychological test results: one
      with most prominent memory impairment (n = 663) and one with most prominent non
      memory impairment (n = 403). We examined associations between cognitive subtype
      and disease progression, as measured with repeated Mini-Mental State Examination
      (MMSE) and Clinical Dementia Rating scale sum of boxes (CDR sob), using linear
      mixed models. Furthermore, we investigated mortality risk associated with
      subtypes using Cox proportional hazard analyses. RESULTS: Patients were 71+/-9
      years old; 541 (51%) were female. At baseline, pooled non-memory patients had
      worse MMSE scores (23.1+/-0.1) and slightly worse CDR sob (4.4+/-0.1) than memory
      patients (MMSE 24.0+/-0.1; p < 0.001; CDR sob 4.1+/-0.1; p < 0.001). During
      follow-up, pooled non-memory patients showed steeper annual decline in MMSE (
      2.8+/-0.1) and steeper annual increase in CDR sob (1.8+/-0.1) than memory
      patients (MMSE - 1.9+/-0.1; pinteraction<0.001; CDR sob 1.3+/-0.1;
      pinteraction<0.001). Furthermore, the non-memory subtype was associated with an
      increased risk of mortality compared with the memory subtype at trend level (HR =
      1.36, CI = 1.00-1.85, p = 0.05). CONCLUSIONS: AD patients with most prominently
      non-memory impairment show faster disease progression and higher risk of
      mortality than patients with most prominently memory impairment.

PMID- 30103315
TI  - TTC7 and Hyccin Regulate Neuronal Abeta42 Accumulation and its Associated Neural
      Deficits in Abeta42-Expressing Drosophila.
AB  - Neuronal amyloid-beta (Abeta) accumulation plays an important role in the
      pathogenesis of Alzheimer's disease (AD). The conformation and toxicity of Abeta
      are regulated by lipids on the plasma membrane. Previously, we found
      downregulation of Rolling Blackout (RBO) or phosphatidylinositol-4-kinase type
      IIIalpha (PI4KIIIalpha) reduces neuronal Abeta accumulation and associated neural
      deficits in a Drosophila model expressing Abeta42. In mammals, the homologs of
      RBO and PI4KIIIalpha were reported to form a plasma membrane-localized complex
      with a scaffold protein TTC7 and cytosolic protein Hyccin/FAM126A to tightly
      control the plasmalemmal level of phosphatidylinositol-4-phosphate. Here, we show
      genetic downregulation of Drosophila TTC7 and Hyccin also reduces neuronal Abeta
      accumulation and associated synaptic and motor defects as well as premature death
      in Abeta42-expressing flies, while overexpression of TTC7 and Hyccin produced the
      opposite effect. These results, together with our previous study, demonstrate
      that RBO/TTC7/PI4KIIIalpha/Hyccin regulate neuronal Abeta accumulation and
      associated neural deficits in the Drosophila model, further supporting the
      RBO/Efr3-PI4KIIIalpha complex as a potential therapeutic target for AD.

PMID- 30103317
TI  - Cerebrovascular Hemodynamics on Transcranial Doppler Ultrasonography and
      Cognitive Decline in Mild Cognitive Impairment.
AB  - BACKGROUND/OBJECTIVE: Vascular risk factors and neurovascular dysfunction may be
      closely related to cognitive impairment and dementia. In this study, we evaluated
      the association between hemodynamic markers and longitudinal cognitive changes in
      patients with mild cognitive impairment (MCI). Furthermore, we investigated
      whether hemodynamic markers could predict the risk of progression to Alzheimer's
      disease (AD) in patients with MCI. METHODS: A total of 68 subjects with amnestic
      MCI were recruited. Using transcranial Doppler (TCD) ultrasonography,
      cerebrovascular reactivity was evaluated with a breath-holding test (breath
      holding index; BHI) in addition to the mean flow velocity (MFV) and pulsatility
      index (PI) of the middle cerebral artery. We followed subjects for 24 months and
      each subject underwent neuropsychological testing and TCD ultrasonography,
      annually. According to the follow-up neuropsychological studies and clinical
      interviews at 12 months, we divided the patients with MCI into two groups:
      patients with stable cognitive performance and patients who progressed to AD.
      RESULTS: Lower BHI and higher PI were observed in patients who progressed to AD.
      The changes of MMSE score over the first 12 months correlated with lower baseline
      MMSE score and changes of MFV and BHI. The changes of MMSE score over 24 months
      were closely related to higher baseline resistance index and PI values.
      Multivariate logistic regression showed that abnormal baseline BHI value could
      predict a conversion from MCI to AD. CONCLUSIONS: We confirmed there is a close
      association between hemodynamic changes represented by TCD markers and cognitive
      decline, supporting the clinical value of hemodynamic markers in predicting MCI
      patients who will progress to AD.

PMID- 30103318
TI  - Psychological Distress, Self-Beliefs, and Risk of Cognitive Impairment and
      Dementia.
AB  - Depressive symptoms and a history of mental disorders are associated with
      increased risk for dementia. Less is known about whether other aspects of
      psychological distress and negative self-beliefs also increase risk. The purpose
      of this research is to examine 1) whether eight aspects of psychological distress
      and self-beliefs (anxiety, negative affect, hostility, anger-in, anger-out,
      hopelessness, pessimism, perceived constraints) are associated with risk of
      incident dementia and cognitive impairment not dementia (CIND), 2) whether the
      associations are independent of depressive symptoms and history of a mental
      health diagnosis, and 3) whether the associations are also independent of
      behavioral, clinical, and genetic risk factors. A total of 9,913 participants
      (60% female) from the Health and Retirement Study completed the baseline
      measures, scored in the non-impaired range of cognition at baseline, and had
      cognitive status assessed across the 6-8-year follow-up. Baseline measures
      included eight aspects of psychological distress and self-beliefs, cognitive
      performance, depressive symptoms, and genetic, clinical, and behavioral risk
      factors. Participants who scored higher on anxiety, negative affect, hostility,
      pessimism, hopelessness, and perceived constraints were at a 20-30% increased
      risk of dementia and a 10-20% increased risk of CIND. The associations held
      controlling for baseline depressive symptoms, history of a mental health
      diagnosis, clinical and behavioral risk factors, and genetic risk. Anger-in and
      anger-out were unrelated to risk of either dementia or CIND. Independent of the
      core experience of depressed affect, other aspects of negative emotionality and
      self-beliefs increase risk of mild and severe cognitive impairment, which
      suggests additional targets of intervention.

PMID- 30103320
TI  - Can a Novel High-Density EEG Approach Disentangle the Differences of Visual Event
      Related Potential (N170), Elicited by Negative Facial Stimuli, in People with
      Subjective Cognitive Impairment?
AB  - BACKGROUND: Studies on subjective cognitive impairment (SCI) and neural
      activation report controversial results. OBJECTIVE: To evaluate the ability to
      disentangle the differences of visual N170 ERP, generated by facial stimuli
      (Anger & Fear) as well as the cognitive deterioration of SCI, mild cognitive
      impairment (MCI), and Alzheimer's disease (AD) compared to healthy controls (HC).
      METHOD: 57 people took part in this study. Images corresponding to facial stimuli
      of "Anger" and "Fear" were presented to 12 HC, 14 SCI, 17 MCI and 14 AD
      participants. EEG data were recorded by using a HD-EEG HydroCel with 256
      channels. RESULTS: Results showed that the amplitude of N170 can contribute in
      distinguishing the SCI group, since statistically significant differences were
      observed with the HC (p < 0.05) and the MCI group from HC (p < 0.001), as well as
      AD from HC (p = 0.05) during the processing of facial stimuli. Noticeable
      differences were also observed in the topographic distribution of the N170
      amplitude, while localization analysis by using sLORETA images confirmed the
      activation of superior, middle-temporal, and frontal lobe brain regions. Finally,
      in the case of "Fear", SCI and HC demonstrated increased activation in the
      orbital and inferior frontal gyrus, respectively, MCI in the inferior temporal
      gyrus, and AD in the lingual gyrus. CONCLUSION: These preliminary findings
      suggest that the amplitude of N170 elicited after negative facial stimuli could
      be modulated by the decline related to pathological cognitive aging and can
      contribute in distinguishing HC from SCI, MCI, and AD.

PMID- 30103321
TI  - Usefulness of Dual-Point Amyloid PET Scans in Appropriate Use Criteria: A
      Multicenter Study.
AB  - BACKGROUND: Biomarkers of neurodegeneration play a major role in the diagnosis of
      Alzheimer's disease (AD). Information on both amyloid-beta accumulation, e.g.,
      from amyloid positron emission tomography (PET), and downstream neuronal injury,
      e.g., from 18F-fluorodeoxyglucose (FDG) PET, would ideally be obtained in a
      single procedure. OBJECTIVE: On the basis that the parallelism between brain
      perfusion and glucose metabolism is well documented, the objective of this work
      is to evaluate whether brain perfusion estimated in a dual-point protocol of 18F
      florbetaben (FBB) PET can be a surrogate of FDG PET in appropriate use criteria
      (AUC) for amyloid PET. METHODS: This study included 47 patients fulfilling
      international AUC for amyloid PET. FDG PET, early FBB (pFBB) PET (0-10 min post
      injection), and standard FBB (sFBB) PET (90-110 min post injection) scans were
      acquired. Results of clinical subjective reports and of quantitative region of
      interest (ROI)-based analyses were compared between procedures using statistical
      techniques such as Pearson's correlation coefficients and t-tests. RESULTS: pFBB
      and FDG visual reports on the 47 patients showed good agreement (k  >  0.74); ROI
      quantitative analysis indicated that both data modalities are highly correlated;
      and the t-test analysis does not reject the null hypothesis that data from pFBB
      and FDG examinations comes from independent random samples from normal
      distributions with equal means and variances. CONCLUSIONS: A good agreement was
      found between pFBB and FDG data as obtained by subjective visual and quantitative
      analyses. Dual-point FBB PET scans could offer complementary information (similar
      to that from FDG PET and FBB PET) in a single procedure, considering pFBB as a
      surrogate of FDG.

PMID- 30103322
TI  - Different Abnormalities of Cortical Neural Synchronization Mechanisms in Patients
      with Mild Cognitive Impairment due to Alzheimer's and Chronic Kidney Diseases: An
      EEG Study.
AB  - This study tested whether resting state alpha rhythms (8-13 Hz) may characterize
      mild cognitive impairment due to Alzheimer's disease (ADMCI) compared with MCI
      due to chronic kidney disease (CKDMCI). Clinical and resting state eyes-closed
      electroencephalographic (rsEEG) rhythms from 40 ADMCI, 29 CKDMCI, and 45
      cognitively normal elderly (Nold) subjects were available in a national archive.
      Age, gender, and education were matched in the three groups, and Mini-Mental
      State Evaluation (MMSE) score was paired in the ADMCI and CKDMCI groups. Delta
      (<4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20
      Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) cortical sources were estimated by
      eLORETA freeware and classified across individuals by area under the receiver
      operating characteristic curve (AUROCC). Compared with Nold group, posterior
      alpha 1 source activities were more reduced in ADMCI than CKDMCI group. In
      contrast, widespread delta source activities were greater in CKDMCI than ADMCI
      group. These source activities correlated with the MMSE score and correctly
      classified between Nold and all MCI individuals (AUROCC = 0.8-0.85) and between
      ADMCI and CKDMCI subjects (AUROCC = 0.75). These results suggest that early AD
      affects cortical neural synchronization at alpha frequencies underpinning brain
      arousal and low vigilance in the quiet wakefulness. In contrast, CKD may
      principally affect cortical neural synchronization at the delta frequencies.
      Future prospective cross-validation studies will have to test these candidate
      rsEEG markers for clinical applications and drug discovery.

PMID- 30103319
TI  - Postsynaptic Proteome of Non-Demented Individuals with Alzheimer's Disease
      Neuropathology.
AB  - Some individuals, here referred to as Non-Demented with Alzheimer's
      Neuropathology (NDAN), retain their cognitive function despite the presence of
      amyloid plaques and tau tangles typical of symptomatic Alzheimer's disease (AD).
      In NDAN, unlike AD, toxic amyloid-beta oligomers do not localize to the
      postsynaptic densities (PSDs). Synaptic resistance to amyloid-beta in NDAN may
      thus enable these individuals to remain cognitively intact despite the AD-like
      pathology. The mechanism(s) responsible for this resistance remains unresolved
      and understanding such protective biological processes could reveal novel targets
      for the development of effective treatments for AD. The present study uses a
      proteomic approach to compare the hippocampal postsynaptic densities of NDAN, AD,
      and healthy age-matched persons to identify protein signatures characteristic for
      these groups. Subcellular fractionation followed by 2D gel electrophoresis and
      mass spectrometry were used to analyze the PSDs. We describe fifteen proteins
      which comprise the unique proteomic signature of NDAN PSDs, thus setting them
      apart from control subjects and AD patients.

PMID- 30103323
TI  - Early Impairments of Hippocampal Neurogenesis in 5xFAD Mouse Model of Alzheimer's
      Disease Are Associated with Altered Expression of SOXB Transcription Factors.
AB  - Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal
      dentate gyrus has been related to cognitive deficits and memory loss in
      neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B
      group of SOX transcription factors play critical roles in regulating neurogenesis
      in the embryonic and adult nervous system, including maintaining the
      multipotency, renewal, and cell fate decision of neural stem/progenitor cells.
      The aim of the present study was to evaluate the expression patterns of selected
      SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which
      represent a transgenic model of AD with a severe and very early development of
      amyloid pathology. Immunohistochemical analysis showed a significant decrease in
      the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within
      the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which
      coincidences with reduced number of doublecortin immunoreactive immature neurons
      found in Tg males. Despite observed changes in expressional pattern of examined
      SOXB proteins, the proliferative capacity evaluated by the number of Ki-67
      immunoreactive cells remained unaffected in transgenic mice of both genders.
      Based on our results, we suggest that SOXB proteins might be considered as new
      biomarkers for the detection of early impairments in adult neurogenesis in
      different animal models or/and new targets in human regenerative medicine.

PMID- 30103325
TI  - Three VCP Mutations in Patients with Frontotemporal Dementia.
AB  - Valosin-containing protein (VCP) is involved in multiple cellular activities.
      Mutations in VCP lead to heterogeneous clinical presentations including inclusion
      body myopathy with Paget's disease of the bone, frontotemporal dementia and
      amyotrophic lateral sclerosis, even in patients carrying the same mutation. We
      screened a cohort of 48 patients with familial frontotemporal dementia (FTD)
      negative for MAPT, GRN, and C9orf72 mutations for other known FTD genes by using
      whole exome sequencing. In addition, we carried out targeted sequencing of a
      cohort of 37 patients with frontotemporal lobar degeneration with Transactive
      response DNA-binding protein 43 (TDP-43) subtype from the Netherlands Brain bank.
      Two novel (p.Thr262Ser and p.Arg159Ser) and one reported (p.Met158Val) VCP
      mutations in three patients with a clinical diagnosis of FTD were identified, and
      were absence in population-match controls. All three patients presented with
      behavioral changes, with additional semantic deficits in one. No signs of Paget
      or muscle disease were observed. Pathological examination of the patient with VCP
      p.Arg159Ser mutation showed numerous TDP-43 immunoreactive (IR) neuronal
      intranuclear inclusions (NII) and dystrophic neurites (DN), while a lower number
      of NII and DN were observed in the patient with the VCP p.Thr262Ser mutation.
      Pathological findings of both patients were consistent with FTLD-TDP subtype D.
      Furthermore, only rare VCP-IR NII was observed in both cases. Our study expands
      the clinical heterogeneity of VCP mutations carriers, and indicates that other
      additional factors, such as genetic modifiers, may determine the clinical
      phenotype.

PMID- 30103326
TI  - Medical and Research Consent Decision-Making Capacity in Patients with
      Alzheimer's Disease: A Systematic Review.
AB  - The capacity to make decisions is an important feature of daily living, which is
      closely linked to proper cognitive functioning. In conditions in which cognitive
      functioning becomes compromised, such as in Alzheimer's disease (AD), decision
      making capacity can also get affected. Especially in AD, this has important
      implications, since over the course of the condition many important clinical
      decisions have to be made. For caregivers as well as physicians, it is sometimes
      difficult to determine how and when to intervene in the decision-making process.
      The aim of this systematic literature review was to identify studies that have
      evaluated medical and research consent decision-making capacity in patients with
      AD. Studies consistently show that decision-making capabilities are impaired in
      patients with AD. The cognitive and neuronal correlates of this process are,
      however, poorly studied. The few studies that investigated correlations have
      shown worse cognitive performance, mainly on the MMSE, to be related to poorer
      decision-making capacity. As most of these correlations have been performed in
      groups combining patients and controls, it remains unknown if these associations
      are disease specific. There is a need to study more systematically the decision
      making process in relation to cognitive functioning and neural correlates to be
      able to develop a framework of decision-making capacity in AD, ultimately aiding
      clinicians and caregivers to understand and evaluate those capabilities in
      patients.

PMID- 30103324
TI  - Metabolic Syndrome and Amyloid Accumulation in the Aging Brain.
AB  - BACKGROUND: Recent studies show links between metabolic syndrome and Alzheimer's
      disease (AD) neuropathology. Understanding the link between vascular-related
      health conditions and dementia will help target at risk populations and inform
      clinical strategies for early detection and prevention of AD. OBJECTIVE: To
      determine whether metabolic syndrome is associated with global cerebral amyloid
      beta (Abeta) positivity and longitudinal Abeta accumulation. METHODS: Prospective
      study of 165 participants who underwent (11)C-Pittsburgh compound B (PiB) PET
      neuroimaging to measure Abeta, from June 2005 to May 2016. Metabolic syndrome was
      defined using the revised Third Adults Treatment Panel of the National
      Cholesterol Education Program criteria. Participants were classified as PiB+/-.
      Linear mixed effects models assessed the relationships between baseline metabolic
      syndrome and PiB status and regional Abeta change over time. RESULTS: A total of
      165 cognitively normal participants of the Baltimore Longitudinal Study of Aging
      (BLSA) Neuroimaging substudy, aged 55-92 years (mean baseline age = 76.4 years,
      85 participants were male), received an average of 2.5 PET-PiB scans over an
      average interval of 2.6 (3.08 SD) years between first and last visits. Metabolic
      syndrome was not associated with baseline PiB positivity or concurrent regional
      Abeta. Metabolic syndrome was associated with increased rates of Abeta
      accumulation in superior parietal and precuneus regions over time in the PiB+
      group. Elevated fasting glucose and blood pressure showed individual associations
      with accelerated Abeta accumulation. CONCLUSION: Metabolic syndrome was
      associated with accelerated Abeta accumulation in PiB+ individuals and may be an
      important factor in the progression of AD pathology.

PMID- 30103328
TI  - Non-Ashkenazi Jewish Origin is Associated with Early Onset Alzheimer's Disease.
AB  - Early-onset Alzheimer's disease (EOAD) accounts for 1-5% of Alzheimer's disease
      cases and is associated with specific ethnicities. It has been our impression
      that non-Ashkenazi Jews have a higher rate of EOAD and we therefore explored this
      hypothesis. We performed a retrospective case control study of EOAD cases
      referred to our cognitive neurology clinic between January 1999 and December
      2016. Patients (n = 129) were compared to age- and geographically-matched
      controls generated from the Second Israeli National Health Survey (n = 1,811).
      Data on country of origin, education, dementia family history, depression, and
      vascular risk factors were compared between the groups. The association of non
      Ashkenazi Jewish heritage and country of origin with EOAD was calculated using a
      logistic multivariate regression model. The EOAD group's mean age was 59.6+/-4.1
      years, with a female predominance (64.3%). The EOAD group had a higher percentage
      of individuals of non-Ashkenazi Jewish origin (64.3% versus 51.4%, p = 0.003) and
      of Yemenite descent in particular (16.28% versus 6.24%, p < 0.001). On multiple
      logistic regression analysis, Yemenite Jewish origin was an independently
      associated with EOAD (OR 2.54, 95% CI 1.4-4.8). There were no significant
      differences in parameters between non-Ashkenazi and Ashkenazi Jews. Only 4.6% of
      EOAD cases had a positive EOAD family history. In conclusion, EOAD is over
      represented among non-Ashkenazi Jews. Yemenite origin is independently associated
      with EOAD and the majority of patients with EOAD have no family history of
      Alzheimer's disease. Further evaluation with genetic studies is warranted.

PMID- 30103329
TI  - Endocytosis and Transcytosis of Amyloid-beta Peptides by Astrocytes: A Possible
      Mechanism for Amyloid-beta Clearance in Alzheimer's Disease.
AB  - Amyloid-beta (Abeta) peptides, Abeta40, Abeta42, and recently Abeta25 - 35, have
      been directly implicated in the pathogenesis of Alzheimer's disease (AD). We have
      previously shown that all three peptides decrease neuronal viability, but Abeta40
      also promotes synaptic disassembling. In this work, we have studied the effects
      of these peptides on astrocytes in primary culture and found that the three Abeta
      peptides were internalized by astrocytes and significantly decreased astrocyte
      viability, while increasing ROS production. Abeta peptide internalization is
      temperature-dependent, a fact that supports the idea that Abeta peptides are
      actively endocytosed by astrocytes. However, inhibiting caveolae formation by
      methyl-beta-cyclodextrin or by silencing caveolin-1 with RNA interference did not
      prevent Abeta endocytosis, which suggests that Abeta peptides do not use caveolae
      to enter astrocytes. Conversely, inhibition of clathrin-coated vesicle formation
      by chlorpromazine or by silencing clathrin with RNA interference significantly
      decreased Abeta internalization and partially reverted the decrease of astrocyte
      viability caused by the presence of Abeta. These results suggest that Abeta is
      endocytosed by clathrin-coated vesicles in astrocytes. Abeta-loaded astrocytes,
      when co-incubated with non-treated astrocytes in separate wells but with the same
      incubation medium, promoted cell death in non-treated astrocytes; a fact that was
      associated with the presence of Abeta inside previously unloaded astrocytes. This
      phenomenon was inhibited by the presence of chlorpromazine in the co-incubation
      medium. These results suggest that astrocyte may perform Abeta transcytosis, a
      process that could play a role in the clearance of Abeta peptides from the brain
      to cerebrospinal fluid.

PMID- 30103327
TI  - Postmortem T2*- Weighted MRI Imaging of Cortical Iron Reflects Severity of
      Alzheimer's Disease.
AB  - The value of iron-based MRI changes for the diagnosis and staging of Alzheimer's
      disease (AD) depends on an association between cortical iron accumulation and AD
      pathology. Therefore, this study determined the cortical distribution pattern of
      MRI contrast changes in cortical regions selected based on the known distribution
      pattern of tau pathology and investigated whether MRI contrast changes reflect
      the underlying AD pathology in the different lobes. T2*-weighted MRI was
      performed on postmortem cortical tissue of controls, late-onset AD (LOAD), and
      early-onset AD (EOAD) followed by histology and correlation analyses. Combining
      ex vivo high-resolution MRI and histopathology revealed that: 1) LOAD and EOAD
      have a different distribution pattern of AD pathological hallmarks and MRI
      contrast changes over the cortex, with EOAD showing more severe MRI changes; 2)
      per lobe, severity of AD pathological hallmarks correlates with iron
      accumulation, and hence with MRI. Therefore, iron-sensitive MRI sequences allow
      detection of the cortical distribution pattern of AD pathology ex vivo.

PMID- 30103330
TI  - Episodic Memory and Learning Dysfunction Over an 18-Month Period in Preclinical
      and Prodromal Alzheimer's Disease.
AB  - Recent meta-analyses suggest that episodic memory impairment associated with
      preclinical Alzheimer's disease (AD) equates to 0.15-0.24 standard deviations
      below that of cognitively healthy older adults. The current study aimed to
      characterize impairments in verbal acquisition and recall detectable at a single
      assessment, and investigate how verbal learning and episodic memory deteriorates
      in preclinical AD. A verbal list-learning task, the International Shopping List
      Test (ISLT), was administered multiple times over an 18-month period, to three
      groups of participants: amyloid-beta negative healthy older adults (Abeta- CN; n
      = 50); Abeta+ positive healthy older adults (preclinical AD; n = 25); and Abeta+
      positive individuals diagnosed with mild cognitive impairment (prodromal AD; n =
      22). At baseline, there was no significant difference between the preclinical AD
      and control groups rate of acquisition, or total and delayed recall, however all
      indices were impaired in prodromal AD. Performance on ISLT total score improved
      in the control group over the 18-month period, but showed a moderate magnitude
      decline in the preclinical AD group (Cohen's d = - 0.63, [- 1.12, - 0.14]) and
      the prodromal AD group (Cohen's d = - 0.36, [- 0.94, 0.22]). No significant
      impairment in acquisition associated with preclinical AD was seen at baseline.
      Individuals with preclinical AD showed a significantly different performance on
      the ISLT total score over an 18-month period, compared to those without abnormal
      Abeta. Individuals with prodromal AD showed substantial impairment on the ISLT at
      baseline and declined to a greater extent over time.

PMID- 30103331
TI  - The Level of Plasma Amyloid-beta40 Is Correlated with Peripheral Transport
      Proteins in Cognitively Normal Adults: A Population-Based Cross-Sectional Study.
AB  - BACKGROUND: Transport proteins, soluble low-density lipoprotein receptor-related
      protein-1 (sLRP1), and soluble receptor of advanced glycation end products
      (sRAGE), play an important role in the clearance of plasma amyloid-beta (Abeta).
      However, their relationship is not clear. OBJECTIVE: The aim was to explore the
      relationship between plasma levels of sLRP1, sRAGE, and Abeta in a cross
      sectional study. METHODS: A total of 1,185 cognitively normal participants (age
      above 40) from a village in the suburbs of Xi'an, China were enrolled from
      October 8, 2014 to March 30, 2015. Plasma Abeta40, Abeta42, sLRP1, and sRAGE were
      tested using a commercial ELISA. Apolipoprotein E (APOE) genotyping was conducted
      using PCR and sequencing. The relationship between plasma levels of sLRP1, sRAGE,
      and Abeta was analyzed using Pearson's correlation analysis and multiple linear
      regression. RESULTS: In the total population, Log sLRP1 and Log sRAGE were
      positively correlated with plasma Abeta40 (r= 0.103, p < 0.001; r= 0.064, p =
      0.027, respectively), but neither were associated with plasma Abeta42. After
      multivariable adjustment in the regression model, Log sLRP1 and Log sRAGE were
      still positively related with plasma Abeta40 (beta= 2.969, p < 0.001; beta=
      1.936, p = 0.017, respectively) but not Abeta42. Furthermore, the positive
      correlations between transport proteins and plasma Abeta40 remained significant
      only in APOEE4 non-carriers after Pearson's analysis and multiple regression
      analysis after stratification by gene status. CONCLUSION: The concentrations of
      plasma sLRP1 and sRAGE had a significant impact on the level of plasma Abeta40 in
      cognitively normal adults, especially in APOEE4 non-carriers. However, the
      mechanism by which the transport proteins are involved in peripheral Abeta
      clearance and the relationship between transporters and amyloid burden in the
      brain needs further validation.

PMID- 30103332
TI  - Common Variant in PLD3 Influencing Cerebrospinal Fluid Total Tau Levels and
      Hippocampal Volumes in Mild Cognitive Impairment Patients from the ADNI Cohort.
AB  - Recent studies found the variants in Alzheimer's disease (AD) risk gene PLD3 were
      associated with cognitive function, but its detailed mechanism before typical AD
      onset was unknown. Our current study examined the impact of PLD3 common variant
      rs11667768 on cerebrospinal fluid (CSF) total-tau and phosphorylated-tau levels
      and structural MRI from the ADNI database. We found rs11667768 was significantly
      associated with CSF total-tau levels and hippocampal volumes at baseline and six
      year follow-up in the total non-demented elderly group and the mild cognitive
      impairment subgroup, indicating a potential role of PLD3 common variants in
      influencing cognitive function through changing CSF total-tau levels and
      hippocampal volumes.

PMID- 30103334
TI  - Is Computerized Working Memory Training Effective in Healthy Older Adults?
      Evidence from a Multi-Site, Randomized Controlled Trial.
AB  - BACKGROUND: Developing effective interventions to attenuate age-related cognitive
      decline and prevent or delay the onset of dementia are major public health goals.
      Computerized cognitive training (CCT) has been marketed increasingly to older
      adults, but its efficacy remains unclear. Working memory (WM), a key determinant
      of higher order cognitive abilities, is susceptible to age-related decline and a
      relevant target for CCT in elders. OBJECTIVE: To evaluate the efficacy of CCT
      focused on WM compared to an active control condition in healthy older adults.
      METHODS: Eighty-two cognitively normal adults from two sites (USA and Sweden)
      were randomly assigned to Cogmed Adaptive or Non-Adaptive (active control) CCT
      groups. Training was performed in participants' homes, five days per week over
      five weeks. Changes in the performance of the Cogmed trained tasks, and in five
      neuropsychological tests (Trail Making Test Part A and Part B, Digit Symbol,
      Controlled Oral Word Association Test and Semantic Fluency) were used as outcome
      measures. RESULTS: The groups were comparable at baseline. The Adaptive group
      showed robust gains in the trained tasks, and there was a time-by-group
      interaction for the Digit Symbol test, with significant improvement only after
      Adaptive training. In addition, the magnitude of the intervention effect was
      similar at both sites. CONCLUSION: Home-based CCT Adaptive WM training appears
      more effective than Non-Adaptive training in older adults from different cultural
      backgrounds. We present evidence of improvement in trained tasks and on a
      demanding untrained task dependent upon WM and processing speed. The benefits
      over the active control group suggest that the Adaptive CCT gains were linked to
      providing a continuously challenging level of WM difficulty.

PMID- 30103333
TI  - Allocentric and Egocentric Spatial Processing in Middle-Aged Adults at High Risk
      of Late-Onset Alzheimer's Disease: The PREVENT Dementia Study.
AB  - Impairments in spatial processing due to hippocampal degeneration have been
      observed in the years immediately preceding the diagnosis of Alzheimer's disease
      (AD) dementia. The demonstration of changes in spatial processing in preceding
      decades would provide a cognitive marker for pre-clinical AD and an outcome
      measure for early intervention trials. The present study examined allocentric and
      egocentric spatial processing in relation to future dementia risk in a middle
      aged cohort. The CAIDE Dementia Risk Score (DRS) was calculated for 188 persons
      aged 40 to 59, of whom 94 had a parent with dementia. Participants underwent the
      Four Mountains Test (4MT) of allocentric spatial processing, the Virtual Reality
      Supermarket Trolley Task (VRSTT) of egocentric spatial processing, and 3T MRI
      scans. A significant negative association was found between the DRS and 4MT
      (Spearman correlation - 0.26, p = 0.0006), but not with the VRSTT. The 4MT was
      also found to be a better predictor of risk than tests of episodic memory, verbal
      fluency, or executive functioning. The results suggest that allocentric rather
      than egocentric processing may be a potential indicator of risk for late-onset
      AD, consistent with the hypothesis that the earliest cognitive changes in AD are
      driven by tau-related degeneration in the medial temporal lobe rather than
      amyloid-only deposition in the medial parietal lobe.

PMID- 30103335
TI  - Social Dysfunction in Older Age and Relationships with Cognition, Depression, and
      Apathy: The GreatAGE Study.
AB  - BACKGROUND: Most studies focused on only one measure of social dysfunction in
      older age, without proper validation and distinction across different dimensions
      including subjectivity, structural, and functional aspects. OBJECTIVE: We sought
      to validate the Social Dysfunction Rating Scale (SDRS) and its factorial
      structure, also determining the association of SDRS with cognitive functions,
      global psychopathology, and social deprivation. METHODS: The SDRS was
      administered to 484 Italian community-dwelling elderly, recruited in the GreatAGE
      study, a population-based study on aging conducted in Castellana Grotte, Bari,
      Southern Italy. We determined objective and subjective psychometric properties of
      SDRS against the gold standard evaluation of social dysfunction according to the
      Semi-structured Clinical Diagnostic Interview for DSM-IV-TR Axis I Disorders
      (SCID-I) criterion. RESULTS: The SDRS showed a moderate accuracy with an optimal
      cut-off of 26 maximized with higher sensitivity (0.74,95% CI:0.63-0.84) than
      specificity (0.57,95% CI:0.50-0.64). A five-factor structure was carried out and
      five dimensions of SDRS were identified (loneliness; social isolation; feeling of
      contribution/uselessness; lack of leisure activities; anxiety for the health).
      Education and global cognitive functions were inversely correlated to SDRS, while
      a direct association with global psychopathology, depression, and apathy was
      found. The prevalence of higher SDRS scores was major in subjects with current
      psychiatric disorders versus other subjects.?Conclusion: The SDRS could be a
      valid instrument to capture both size and quality of social dysfunction, both in
      subjects with psychiatric disorders and in normal subjects. Several categories of
      social dysfunction differed only in the degree of health deprivation, not in
      social or material deprivation.

PMID- 30103336
TI  - Patterns of Regional Cerebral Blood Flow as a Function of Age Throughout the
      Lifespan.
AB  - BACKGROUND: Understanding the influence of aging on the brain remains a challenge
      in determining its role as a risk factor for Alzheimer's disease. OBJECTIVE: To
      identify patterns of aging in a large neuroimaging cohort. METHODS: A large
      psychiatric cohort of 31,227 individuals received brain SPECT at rest and during
      a concentration task for a total of 62,454 scans. ANOVA was done to identify the
      mean age trends over the course of the age range in this group, 0-105 years. A
      regression model in which brain SPECT regions of interest was used to predict
      chronological age (CA) was then utilized to derive brain estimated age (BEA). The
      difference between CA and BEA was calculated to determine increased brain aging
      in common disorders in our sample such as depression, dementia, substance use,
      and anxiety. RESULTS: Throughout the lifespan, variations in perfusion were
      observed in childhood, adolescence, and late life. Increased brain aging was seen
      in alcohol use, cannabis use, anxiety, bipolar, schizophrenia, attention
      deficit/hyperactivity disorder, and in men. CONCLUSION: Brain SPECT can predict
      chronological age and this feature varies as a function of common psychiatric
      disorders.

PMID- 30103337
TI  - Greg Kennedy, BSc (Hons), Recipient of the 2018 Alzheimer Award.

PMID- 30103339
TI  - Computational Analysis of Transcriptional Regulation Sites at the HTT Gene Locus.
AB  - BACKGROUND: Huntington's disease is a late onset neurological disorder caused by
      a trinucleotide CAG repeat expansion mutation in the HTT gene encoding for the
      protein huntingtin. Despite considerable ongoing research, the wild-type function
      of huntingtin is not yet fully understood. OBJECTIVE: To improve knowledge of HTT
      gene regulation at the transcriptional level and inform future studies aimed at
      uncovering the HTT gene's normal function. METHODS: The HTT gene region was
      functionally characterized through an in silico analysis using publicly available
      data sets. ChIP-seq data sets and the online STRING database were used to
      identify putative transcription factor binding sites (TFBSs) and protein-protein
      interactions within the HTT promoter region. siRNA-mediated knockdown and ChIP
      qPCR of STAT1, a TF identified from the in silico analysis, were used to validate
      the bioinformatics screen. RESULTS: 16 regions containing potential regulatory
      genomic markers were identified. TFBSs for 59 transcription factors (TFs) were
      detected in one or more of the 16 candidate regions. Using these TFs, 15 clusters
      of protein-protein interactions were identified using STRING. siRNA-mediated
      knockdown of STAT1 resulted in an increase in HTT expression, and ChIP-qPCR
      detected enrichment of STAT1 binding at one of the predicted regions. These
      assays confirmed the utility of the bioinformatic analysis. CONCLUSIONS: Putative
      regulatory regions outside of the immediate HTT promoter region have been
      identified with specific protein-protein interactions. Future work will focus on
      in vitro and in vivo studies to examine the effect of modulating identified TFBSs
      and altering the levels of specific TFs of interest in regulating HTT gene
      expression.

PMID- 30103340
TI  - Vocalisation as a Viable Assessment for Phenotyping Minipigs Transgenic for the
      Huntington Gene?
AB  - BACKGROUND: Large animal models, such as the transgenic (tg) Huntington disease
      (HD) minipig, have been proposed to improve translational reliability and
      assessment of safety, efficacy and tolerability in preclinical studies. Minipigs
      are characterised by high genetic homology and comparable brain structures to
      humans. In addition, behavioural assessments successfully applied in humans could
      be explored in minipigs to establish similar endpoints in preclinical and
      clinical studies. Recently, analysis of voice and speech production was
      established to characterise HD patients. OBJECTIVE: The aim of this study was to
      investigate whether vocalisation could also serve as a viable marker for
      phenotyping minipigs transgenic for Huntington's disease (tgHD) and whether tgHD
      minipigs reveal changes in this domain compared to wildtype (wt) minipigs.
      METHODS: While conducting behavioural testing, incidence of vocalisation was
      assessed for a cohort of 14 tgHD and 18 wt minipigs. Statistical analyses were
      performed using Fisher's Exact Test for group comparisons and McNemar's Test for
      intra-visit differences between tgHD and wt minipigs. RESULTS: Vocalisation can
      easily be documented during phenotyping assessments of minipigs. Differences in
      vocalisation incidences across behavioural conditions were detected between tgHD
      and wt minipigs. Influence of the genotype on vocalisation was detectable during
      a period of 1.5 years. CONCLUSION: Vocalisation may be a viable marker for
      phenotyping minipigs transgenic for the Huntington gene. Documentation of
      vocalisation provides a non-invasive opportunity to capture potential disease
      signs and explore phenotypic development including the age of disease
      manifestation.

PMID- 30103341
TI  - Marriage as Protector for Nursing Home Admission in Huntington's Disease.
AB  - BACKGROUND: Huntington's disease is a progressive, incurable neurodegenerative
      disorder and it is not possible to delay onset or progression of the disease.
      Consequently, the disease leads to functional decline and loss of independency
      and finally to institutionalization. OBJECTIVE: The aim of this study is to
      identify factors which are associated with nursing home admission in patients
      with Huntington's disease. METHODS: The Unified Huntington's Disease Rating Scale
      (UHDRS) and the UHDRS-For Advanced Patients (UHDRS-FAP) were administered in 28
      nursing home residents and 12 patients receiving day-care. Comparisons between
      the two groups were performed using Mann-Whitney U tests and Chi-square tests.
      The significantly different findings were fitted in individual univariate
      logistic regression models to determine which components were most predictive of
      institutionalization. RESULTS: Day-care participants were more often married than
      nursing home residents (p = 0.006) and were functionally more independent: the
      Functional Assessment Scale (p = 0.022) of the UHDRS was significantly higher.
      Not being married was more predictive for nursing home admission than functional
      capacity in the regression models. CONCLUSIONS: Our results suggest that being
      married is protective for nursing home placement. Possibly, a caregiver living
      with a patient can assist with activities of daily living which the patient could
      not have done independently, resulting in being able to live at home longer.
      Providing support to unmarried patients, who do not have a caregiver living with
      them, by home care services specialized in Huntington's disease might increase
      the chance of the best possible care before institutionalization and postpone
      nursing home admission.

PMID- 30103342
TI  - Huntington's Disease Clinical Trials Corner: August 2018.
AB  - In the third edition of the Huntington's Disease Clinical Trials Corner we list
      all currently registered and ongoing clinical trials, expand on the SIGNAL trial
      (NCT02481674), and cover the recently finished CREST-E trial (NCT00712426).

PMID- 30103344
TI  - Improving effects of Echium amoenum aqueous extract on rat model of Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) is a progressive neurodegenerative disorder greatly
      accompanied by oxidative stress and acetylcholine reduction in synaptic cleft
      that leads to dementia. Previously approved there is correlation between nucleus
      basalis of Meynert (NBM) degeneration and loss of memory, learning ability and
      thought. The aim of this study was to investigate improving effects of Echium
      amoenum aqueous extract on memory deficient, pathophysiological and oxidative
      damages imposed by NBM lesion in rats as documented AD model. Results showed NBM
      destruction causes hash oxidative stress that possibly leads to neurodegeneration
      in hippocampus tissue. Orally administration of plant extract significantly
      reduced oxidative stress by reactive molecules scavenging that resulted to
      decrease lipid peroxidation also. Plant extract treatment inhibited acetylcholine
      esterase enzyme (more than 5 folds) in hippocampus tissue related to NBM lesioned
      rats. Histological studies approved NBM lesion causes harsh neurodegeneration in
      hippocampus tissue possibly by acetylcholine reduction that was compensated by
      plant extract protective effects. Interestingly improving effects of plant in
      molecular level causes improved spatial learning ability in Morris water maze
      test. By considering pathophysiological and molecular similarities between AD and
      NBM lesion model, E. amoenum could be used as a therapeutic adjuvant in patients
      suffering from Alzheimer or similar cognitive disorders.

PMID- 30103345
TI  - In vivo one-photon confocal calcium imaging of neuronal activity from the mouse
      neocortex.
AB  - In vivo calcium imaging is a powerful tool used to record neuronal activity from
      living animals. For this purpose, two-photon excitation laser-scanning microscopy
      is commonly used because of the optical accessibility of deep tissues. In this
      study, we report that one-photon confocal scanning laser microscopy, when
      optimally tuned, is also applicable for in vivo calcium imaging from the
      superficial layer of the neocortex. By combining a Nipkow-disk confocal unit with
      a fluorescence stereo zoom microscope and a high numerical aperture objective, we
      succeeded in recording the fluorescence signal of individual cells at a depth of
      up to 160 MUm in brain tissues, which corresponds to layer II of the mouse
      neocortex. In fact, we conducted in vivo functional multineuron calcium imaging
      and simultaneously recorded spontaneous activity from more than 100 neocortical
      layer II neurons. This one-photon confocal system provides a simple, low-cost
      experimental platform for time-lapse imaging from living animals.

PMID- 30103346
TI  - Emotional system in complex cognitive activities of working memory: A literature
      review of its role.
AB  - Cognitive processing is needed to elicit emotional responses. At the same time,
      emotional responses modulate and guide cognition to enable adaptive responses to
      the environment. However, most empirical studies and theoretical models of
      cognitive functions have been investigated without taking into account emotion,
      which is considered interference that is counterproductive to the correct
      functioning of the cognitive system. To understand how complex behaviors are
      carried out in the brain, an understanding of the interactions between emotion
      and cognition may be indispensable. Given the enormous scope of this topic for
      both cognition and emotion, these concepts will not be further defined here;
      instead, this review will be relatively narrow in scope and will emphasize
      several brain systems involved in the interactions between emotion and working
      memory because an important dimension of cognition involves working memory
      function. In attempting to understand the relationship between emotion and
      working memory, we will describe the projections of a set of brain structures
      that support our emotional life and the neuromodulator dopamine (which is also
      involved in emotion processing and incentive motivational behavior) in the
      prefrontal cortex. According to the literature, working memory engages the
      cortical regions. Thus, the prefrontal cortex, particularly the dorsolateral
      prefrontal cortex (DLPFC), although commonly viewed as a purely cognitive area,
      provides a test for the hypothesis that working memory and emotion are strongly
      integrated in the brain. In this review, we provide an overview of
      neuropsychological, neuroanatomical and molecular evidence, with the aim of
      establishing the extent to which working memory and emotion are related.

PMID- 30103347
TI  - Working-memory evaluation based on EEG signals during n-back tasks.
AB  - Working memory is the cognitive process of receiving, processing, and
      communicating information. Early evaluation and training may help to prevent a
      marked decline in working-memory ability. The aim of this study was to establish
      an n-back task system for objectively evaluating the working-memory ability based
      on the theta power, the gamma power, and the degree of theta-gamma
      synchronization. Our experiments were divided into four memory loads (1-back to 4
      back) and further divided into digital and matrix stimulation modes. The gamma
      band was divided into three components (gamma1: 30-50 Hz, gamma2: 50-70 Hz, and
      gamma3: 70-90 Hz). The study recruited 23 healthy young subjects. The obtained
      results indicate that accuracy rates might be inappropriate for assessing the
      working memory. The theta power relates to working-memory recognition while the
      gamma power varied with the memory load. Besides, a higher load level should be
      more appropriate for assessing the working-memory ability. Finally, the number of
      theta-gamma3 couplings was highest between the frontal area and Pz and O2. In
      summary, the results of this study may be useful in multiple evaluations of
      working memory, and may lead to a wider variety of clinical applications in the
      future.

PMID- 30103350
TI  - Mastication and Oral Motor Function in McArdle Disease: Patient Reported
      Complaints.
AB  - BACKGROUND: Exertional myalgia and cramps of the limb and trunk muscles are
      typical in McArdle disease, but mastication and oral motor limitations have not
      been systematically investigated before. OBJECTIVE: Determine the reported
      prevalence and characteristics of limitations on oral motor activities,
      mastication, swallowing, and other oral motor activities in patients with McArdle
      disease. METHODS: An observational study was carried out in 28 patients using a
      standardised questionnaire on mastication and oral motor function. RESULTS: 57%
      of the participants reported difficulties with mastication. Muscle cramps during
      mastication occurred in 57% of the patients. A feeling that food remains in the
      throat occurred in 32%. Adaptations during mastication were needed in 42% of the
      patients. Mastication difficulties, muscle cramps during mastication and
      mastication adjustments were inversely correlated with age (r2 = - 0.445, p <
      0.05; r2 = - 0.509, p < 0.01; r2 = - 0.456, p < 0.05). Feeling of food remaining
      in throat, cramps during mastication and during other oral motor muscle
      activities, were correlated with disease severity (r2 = 0.476, p < 0.01; r2 =
      0.463, p < 0.01; r2 = 0.461, p < 0.01; r2 = 0.432, p < 0.05). CONCLUSIONS: In
      short, reported mastication difficulties are prevalent in people with McArdle
      disease, most frequently in younger people. Therefore, awareness of mastication
      and oral motor problems is required.

PMID- 30103349
TI  - MRI-Guided Biopsy as a Tool for Diagnosis and Research of Muscle Disorders.
AB  - BACKGROUND: Sampling error is a common problem in muscle biopsies. MRI-guided
      biopsy allows verification of biopsy site during the procedure, which may reduce
      sampling error in patients with focal disease. OBJECTIVES: To describe the
      technique for MRI-guided muscle biopsy and discuss potential applications.
      METHODS: Axial MRI images were acquired to determine the target site for muscle
      biopsy. Needle trajectory was planned on 3D T1 weighted imaging and a MRI-guided
      biopsy of the vastus lateralis was performed in 13 FSHD patients. RESULTS: An
      adequate amount of muscle tissue was obtained in all participants, and MRI-guided
      biopsy succeeded in reaching focal target sites. However, symptomatic hematomas
      were observed in 2/13 patientsDiscussion:MRI-guided biopsy has a higher
      complication rate compared to traditional needle biopsy, most likely due to
      proximity to blood vessels in combination with the vacuum-assisted suction of the
      MRI-guided technique. We recommend that this technique is reserved for select
      diagnostic cases and research questions, with careful assessment of vasculature
      and reduced suction levels.

PMID- 30103351
TI  - No Significant Difference in Cognitive Decline and Mortality between Parkinson's
      Disease Dementia and Dementia with Lewy Bodies: Naturalistic Longitudinal Data
      from the Swedish Dementia Registry.
AB  - BACKGROUND: Whether dementia with Lewy bodies (DLB) and Parkinson's disease
      dementia (PDD) are distinct disorders or two subtypes of the same entity, is not
      yet fully understood. There is a dearth of knowledge on differences in
      longitudinal clinical outcomes between DLB and PDD. OBJECTIVE: We aimed to
      compare longitudinal trend of cognitive decline, mortality, and their determinant
      factors between patients with DLB and PDD. METHODS: At baseline, we recruited
      1110 DLB, and 764 PDD patients registered in the Swedish dementia registry
      (SveDem) during 2007-2015. Cognitive status was assessed at baseline and each
      follow-up visit by mini-mental state examination (MMSE). At least one follow-up
      MMSE was available for 411 (37.0%) DLB and 229 (30.0%) PDD patients. Rate of
      cognitive decline and mortality risk were compared between the two groups.
      RESULTS: After an average of 2-years, the rate of cognitive decline did not
      differ between DLB (1.1 MMSE unit/year) and PDD (1.2 MMSE unit/year) groups (p =
      0.970). There was no significant difference in the median survival time between
      DLB (4.0 years) and PDD (4.1 years) groups (Log rank p = 0.614). Antipsychotic
      drug use in DLB and larger number of medications in PDD were the most important
      determinants of faster annual cognitive decline. CONCLUSIONS: Our findings from
      real-world clinical practice demonstrated that the rate of cognitive decline and
      mortality do not differ significantly between DLB and PDD at least over 2 years,
      yet, various factors might determine clinical outcome in these two groups. It
      seems that DLB and PDD are probably similar synucleinopathies, with phenotypical
      variations in the order of manifestations rather than course of progression and
      clinical outcome.

PMID- 30103353
TI  - Postnatal blood pressure in the preterm small for gestational age neonate.
AB  - OBJECTIVE: Determine how blood pressure differs in premature infants born small
      for gestational age (SGA). DESIGN: A retrospective study was conducted on inborn
      infants 24-32 weeks gestation. Mean arterial blood pressure (MAP) was collected
      and averaged every 12 h for the first 96 h of life. For each time point, the
      difference MAP in SGA vs. AGA infants was evaluated with t-testing. Linear mixed
      effects modeling was performed to model MAP over time accounting for GA, BW,
      gender, and SGA status. RESULTS: 356 subjects were evaluated. 52 (14.6% ) were
      SGA. SGA infants were smaller, more likely male, exposed to maternal
      hypertension, born via caesarian section, and have chronic lung disease and
      retinopathy of prematurity. MAP in the SGA group more closely matched the MAP of
      AGA babies of similar GA for the first 24 h of life. Subsequently, SGA infants
      had lower MAPs more closely resembling their weight-matched counterparts. Mixed
      modeling showed GA to be significant, p <  0.0001 while BW though still
      marginally significant had less of an effect, p = 0.049. CONCLUSION: SGA infants
      have blood pressure that is strongly associated with GA in the first 24 hours of
      life, but then fails to increase at the same rate as their AGA counterparts.

PMID- 30103352
TI  - Medication reconciliation and review for older emergency patients requires
      improvement in Finland.
AB  - BACKGROUND: 10-30% of hospital stays by older patients are drug-related. The
      admission phase is important for identifying drug-related problems, but taking an
      incorrect medication history often leads to medication errors. OBJECTIVES: To
      enhance medication history recording and identify drug-related problems (DRPs) of
      older patients admitted to emergency departments (EDs). METHODS: DRPs were
      identified by pharmacists-led medication reconciliation and review procedures in
      two EDs in Finland; Helsinki University Hospital (HUS), and Kuopio University
      Hospital (KUH). One-hundred-and-fifty patients aged >=65-years, living at home
      and using >=6 medicines were studied. RESULTS: 100% of patients (N = 75) in HUS
      and 99% in KUH (N = 75), had discrepancies in their admission-medication chart
      recorded by the nurse or physician. Associations between admission-diagnosis and
      drug-related problems were found in 12 patients (16%) in HUS and 22 patients
      (29%) in KUH. Of these, high-alert medications (e.g. antithrombotics,
      cytostatics, opioids) were linked to eight patients (11%) in HUS and six patients
      (8%) in KUH. Other acute DRPs were identified in 19 patients (25%) in HUS and 54
      patients (72%) in KUH. Furthermore, 67 patients (89%) in HUS and all patients in
      KUH had non-acute DRPs. CONCLUSIONS: Medication reconciliation and review at
      admission of older ED patients requires improvement in Finland.

PMID- 30103354
TI  - Effect of fluctuation of oxygenation and time spent in the target range on
      retinopathy of prematurity in extremely low birth weight infants.
AB  - BACKGROUND: The association between saturation of peripheral oxygenation (SpO2)
      fluctuation and severity of retinopathy of prematurity (ROP) is well elucidated
      in extremely low birth weight (ELBW) infants. Time spent in the Target range of
      SpO2 is also associated with the severity of ROP. METHODS: In a prospective
      observational study, the SpO2 of all ELBW infants admitted to our unit were
      monitored for the first four weeks of life, and averaged every minute for
      analysis. The percent time spent at SpO2 <90%, 90-95%, and >95% and weekly SpO2
      fluctuations [as SpO2 coefficient of variation (CoV)] were calculated. RESULTS:
      During the study period 21 infants had moderate to severe ROP and 35 infants
      served as controls. Infants with moderate to severe ROP were smaller and younger
      than their controls [676+/-124 grams vs. 796+/-148 grams (p < 0.001); and 24.0+/
      1.0 weeks vs. 25.0+/-1.7 weeks (p < 0.001) respectively]. There were no
      significant differences in time spent in the 90-95% range between groups (p =
      0.66). However there was a significant increase in weekly SpO2 CoV in infants
      with moderate to severe ROP vs. controls (p = 0.007). CONCLUSION: In ELBW
      infants, there was an association between SpO2 fluctuation during the first four
      weeks of life and severity of ROP, although, no association was established with
      time spent in the target range of SpO2.

PMID- 30103348
TI  - Centronuclear myopathies under attack: A plethora of therapeutic targets.
AB  - Centronuclear myopathies are a group of congenital myopathies characterized by
      severe muscle weakness, genetic heterogeneity, and defects in the structural
      organization of muscle fibers. Their names are derived from the central position
      of nuclei on biopsies, while they are at the fiber periphery under normal
      conditions. No specific therapy exists yet for these debilitating diseases.
      Mutations in the myotubularin phosphoinositides phosphatase, the GTPase dynamin
      2, or amphiphysin 2 have been identified to cause respectively X-linked
      centronuclear myopathies (also called myotubular myopathy) or autosomal dominant
      and recessive forms. Mutations in additional genes, as RYR1, TTN, SPEG or
      CACNA1S, were linked to phenotypes that can overlap with centronuclear
      myopathies. Numerous animal models of centronuclear myopathies have been studied
      over the last 15 years, ranging from invertebrate to large mammalian models.
      Their characterization led to a partial understanding of the pathomechanisms of
      these diseases and allowed the recent validation of therapeutic proof-of
      concepts. Here, we review the different therapeutic strategies that have been
      tested so far for centronuclear myopathies, some of which may be translated to
      patients.

PMID- 30103355
TI  - Reduction thermal damage to cortical bone using ultrasonically-assisted drilling.
AB  - BACKGROUND: Thermal damage induced by bone drilling is a common problem during
      surgical procedures. A recent and promising method utilizes high-frequency low
      amplitude vibration in the feed direction during drilling and has the potential
      to reduce drilling temperature, minimizing the risk of thermal damage. OBJECTIVE:
      The purpose of this study was to investigate the effects of ultrasonically
      assisted drilling (UAD) on cortical bone temperature. METHODS: A series of
      experiments was conducted to compare the cortical bone temperature during UAD
      with that during conventional drilling (CD). A thermo-mechanical 3D finite
      element model (FEM) of UAD was developed, using ABAQUS, to help understand
      temperature changes during drilling of cortical bone. The numerical simulation
      results of FEM showed good agreement with the experimental data. Subsequently, a
      predictive model was developed for bone temperature during drilling, using
      multiple regression analysis based on the results from numerical simulation.
      RESULTS: The results showed drill diameter had the greatest influence on drilling
      temperature, followed by the rotational speed of the drill. Additionally, the
      variation of vibration frequency had more influence on the drilling temperature
      than did the amplitude. CONCLUSIONS: Ultrasonically-assisted drilling is helpful
      to lower drilling temperature to reduce the thermal damage of bone tissue.

PMID- 30103356
TI  - Controlling of smart home system based on brain-computer interface.
AB  - BACKGROUND: Brain computer interface (BCI) technology is a communication and
      control approach. Up to now many studies have attempted to develop an EEG-based
      BCI system to improve the quality of life of people with severe disabilities,
      such as amyotrophic lateral sclerosis (ALS), paralysis, brain stroke and so on.
      The proposed BCIBSHS could help to provide a new way for supporting life of
      paralyzed people and elderly people. OBJECTIVE: The goal of this paper is to
      explore how to set up a cost-effective and safe-to-use online BCIBSHS to
      recognize multi-commands and control smart devices based on SSVEP. METHODS: The
      portable EEG acquisition device (Emotiv EPOC) was used to collect EEG signals.
      The raw signals were denoised by discrete wavelet transform (DWT) method, and
      then the canonical correlation analysis (CCA) method was used for feature
      extraction and classification. Another part is the control of smart home devices.
      The classification results of SSVEP can be translated into commands to control
      several devices for the smart home. RESULTS: Here, the Power over Ethernet (PoE)
      technology was utilized to provide electrical energy and communication for those
      devices. During online experiments, four different control commands have been
      achieved to control four smart home devices (lamp, web camera, guardianship
      telephone and intelligent blinds). Experimental results showed that the online
      BCIBSHS obtained 86.88 +/- 5.30% average classification accuracy rate.
      CONCLUSION: The BCI and PoE technology, combined with smart home system,
      overcoming the shortcomings of traditional systems and achieving home
      applications management rely on EEG signal. In this paper, we proposed an online
      steady-state visual evoked potential (SSVEP) based BCI system on controlling
      several smart home devices.

PMID- 30103357
TI  - The role of the smoking on the mechanical properties of the human lung.
AB  - The mechanical functions of the lungs are concerned with ventilating the alveoli
      and aiding venous return to the heart. The mechanical properties of the lung
      allow this to be fulfilled with a very small expenditure of energy. Smoking via
      chronic obstructive pulmonary disease (COPD) can affect this mechanical function
      through the alteration of the mechanical properties of the lung tissue. So far,
      no study has been conducted to experimentally compare the in vitro mechanical
      properties of the human lung tissue among the healthy nonsmokers and unhealthy
      smokers. Therefore, there is a paucity of knowledge on how the macro-mechanical
      properties of the lung tissue as a consequence of at least 7 years of smoking can
      alter. This study was, hence, aimed at performing a comparative study to compare
      the linear elastic and nonlinear hyperelastic mechanical properties of the
      healthy nonsmokers and unhealthy smokers' lung using uniaxial tensile testing
      under two different loading directions, i.e., the axial and transversal. To do
      that, the COppm (Carbon Monoxide part per million) and %COHb (blood
      Carboxyhemoglobin) of 18 cadaveric individuals, including 9 nonsmokers and 9
      smokers were measured. The COppm and %COHb were found to be 26 +/- 1.58 (Mean +/-
      SD) and 4 +/- 1.16 for the smokers and 4.79 +/- 0.25 and 1.27 +/- 0.16 for the
      nonsmokers, respectively. The lung tissues were excised from the cadavers and
      mounted on the uniaxial tensile test machine under the loading rate of 5 mm/min.
      The stress-strain data of the tissues revealed the axial elastic modulus of 58 +/
      4.21 and 142 +/- 8.84 kPa for the nonsmokers and smokers' lungs, respectively.
      Similarly, the transversal elastic modulus of 53 +/- 7.16 and 127 +/- 11.15 kPa
      were found for the nonsmokers and smokers' lungs, respectively. The results
      revealed a significant difference between the axial and transversal mechanical
      properties of the nonsmokers and smokers' lung tissues (p< 0.05, post hoc Scheffe
      method). The hyperelastic material coefficients of the lung tissues were also
      calculated and reported. These findings have implications not only for
      understanding the smoking role on the mechanical properties of the lung tissue
      but also to give rise to novel therapeutic strategies for the management of the
      disease and prevention of smoking addiction.

PMID- 30103358
TI  - The effects of instrument-assisted soft tissue mobilization on active range of
      motion, functional fitness, flexibility, and isokinetic strength in high school
      basketball players.
AB  - Although many studies have focused on stretching techniques for athletes, no
      comprehensive studies have investigated the use of the instrument-assisted soft
      tissue mobilization (IASTM) technique in young basketball players. The active
      properties of muscle and subjective reporting of functional ability were used to
      identify the effects of IASTM on the calf muscle. Active range of motion (AROM),
      functional fitness, and isokinetic lower strength in the knees and ankles were
      measured in 40 healthy young basketball players. They were divided into the IASTM
      group (n= 20) and a control group (CG, n= 20). Twenty asymptomatic young
      basketball players were treated with IASTM six times per week for 8 weeks. The
      remaining 20 participants did not receive a treatment intervention between tests
      and served as the control. Ankle AROM (two knee positions of 0? and 45? flexion),
      functional fitness at the knee and ankle (side-step and vertical jump), and
      isokinetic peak torque were determined during ankle dorsiflexion (DF) and plantar
      flexion (PF) and knee extension (EX) and flexion (FX). The data were analyzed
      using repeated-measures analysis of variance. Significant differences were
      observed between the two groups in IASTM and control AROM 0? knee flexion (right:
      DF; p< 0.001 and PF; p< 0.001; left: DF; p< 0.001 and PF; p= 0.011), AROM 45?
      knee flexion (right: DF; p< 0.001 and PF; p= 0.009; left: DF; p< 0.001 and PF; p=
      0.001), functional fitness (side step; p= 0.001, sit and reach; p= 0.025,
      vertical jump; p= 0.001), ankle isokinetic strength 30?/sec (right: DF; p= 0.001
      and PF; p= 0.001; left: DF; p< 0.001 and PF; p= 0.002), ankle isokinetic strength
      120?/sec (right: DF; p= 0.049 and PF; p= 0.001; left: DF; p= 0.023 and PF; p<
      0.001), knee isokinetic strength 60?/sec (right: EX; p= 0.001, FX; p= 0.001 and
      hamstring and quadriceps ratio [H/Q]; p= 0.001, left: EX; p= 0.001, FX; p= 0.001
      and H/Q; p= 0.001), and knee isokinetic strength 180?/sec (right: EX; p= 0.001,
      FX; p= 0.001 and H/Q; p= 0.001; left: EX; p= 0.001, FX; p= 0.010 and H/Q; p=
      0.001). These results suggest that IASTM improves functional fitness and lower
      body muscle strength in young basketball players.

PMID- 30103359
TI  - Psychological health and occupational therapists: Burnout, engagement and work
      addiction.
AB  - BACKGROUND: Burnout, work engagement and work addiction are all considered
      components of psychological health in the workplace. Past research indicates that
      healthcare providers face significant challenges to their psychological wellbeing
      in the workplace. OBJECTIVE: This study sought to determine the extent of these
      components in a sample of Canadian occupational therapists. METHODS: An anonymous
      electronic survey including standardized measures of burnout, work engagement and
      work addiction. RESULTS: Participants' scores at times differed from previous
      research on burnout in the occupational therapy profession in that they
      demonstrated higher depersonalization scores and lower emotional exhaustion
      scores. Relationships emerged among a number of elements within the various
      measures, and participants' age and years of experience. Scores indicating a risk
      of burnout and work addiction clustered at certain times across participants'
      years of experience, and scores for vigour were low in comparison to an
      international study of healthcare workers. However, scores in other elements were
      high (for example, dedication and personal accomplishment), which theorists
      propose may serve a protective role in mitigating high scores in negative
      elements. CONCLUSIONS: Findings demonstrate a risk for diminished work-related
      psychological health and point to key areas for further investigation around
      which targeted interventions could be organized for members of the occupational
      therapy profession.

PMID- 30103360
TI  - Working in a cocoon: (Co)working conditions of office nomads - a health related
      qualitative study of shared working environments.
AB  - BACKGROUND: The flexible working and business model of coworking spaces inherits
      the provision of workspace and further the construction of a network for
      entrepreneurs, creative and knowledge workers. Until now, research on coworking
      spaces is scarce in the field of health sciences. OBJECTIVE: This study
      investigated reasons and motives for working in coworking spaces and working
      conditions under health related aspects. Demands and resources while working in
      coworking spaces were analyzed according to a theoretical model for (Job-demands
      resources model - JDR) perceived working conditions. METHODS: Twenty semi
      structured qualitative interviews were conducted with coworkers (n = 14) and
      coworking operators (n = 6) in Berlin, Hamburg, and Munich. Participants were
      asked to describe the reasons and motivations for working in coworking spaces and
      their perceived working conditions. Transcripts were analyzed according to
      content analysis. RESULTS: The most mentioned reason for using coworking spaces
      were the community aspect (n = 15) followed by the alternative to home office (n
      = 12). Negative job demands seem to result from unfavorable ergonomic conditions,
      working disruptions, miscommunications and missing privacy. Time flexibility,
      social surrounding and increased productivity were interpreted as job resources.
      CONCLUSIONS: These results can be seen as a basis for further quantitative
      research in order to generalize these findings, by testing hypotheses and develop
      workplace-related concepts for health management.

PMID- 30103361
TI  - Using an adapted Delphi process to develop a survey evaluating employability
      assessment in total and permanent disability insurance claims.
AB  - BACKGROUND: No research has been undertaken about employability assessment of
      total and permanent disability (TPD) insurance claims. Employability assessment
      provides vocational information to life insurers to help decide claims. To
      determine how helpful employability assessment is, a new measure was needed to
      survey insurers. OBJECTIVE: To generate survey items by harnessing the knowledge
      and agreement of rehabilitation advisors with expertise in employability
      assessment. METHODS: A panel of 10 (89% of eligible Australian rehabilitation
      advisors) participated in an adapted three-round Delphi process. Rounds 2 and 3
      were incorporated into a novel real-time card sort format. RESULTS: From 94
      potential items submitted for first round qualitative analysis, 36 items in four
      domains-quality, content, utility, and claims-were generated. Two quantitative
      ranking rounds in one face-to-face session produced a 21-item prototype. The
      final electronic survey instrument contained 11 sections seeking insurer
      demographics and feedback on: external providers; employability assessment
      concepts, components, quality, and usefulness; functional, occupational, labor
      market items; and finally, cost and type. Our Delphi process was anonymous,
      completed in four weeks with 100% response rate and 75% agreement. More time
      between Rounds 2 and 3 would enhance statistical analysis. CONCLUSIONS: Our
      adapted Delphi methodology for survey item generation is generalizable for any
      panel able to meet in person.

PMID- 30103362
TI  - Borg CR-10 scale as a new approach to monitoring office exercise training.
AB  - BACKGROUND: There are many potential training exercises for office workers in an
      attempt to prevent musculoskeletal disorders. However, to date a suitable tool to
      monitor the perceived exertion of those exercises does not exist. OBJECTIVE: The
      primary objective of this study was to examine the validity and reliability of
      the Borg CR-10 scale to monitor the perceived exertion of office exercise
      training. METHODS: The study involved 105 staff members employed in a government
      office with an age range from 25 to 50 years. The Borg CR-10 scale was self
      administered two times, with an interval of two weeks in order to evaluate the
      accuracy of the original findings with a retest. Face validity and content
      validity were also examined. RESULTS: Reliability was found to be high for the
      Borg CR-10 scale (0.898). Additionally a high correlation between the Borg CR-10
      scale and Visual Analog Scale (VAS) was identified (rs = 0.754, P < 0.01).
      CONCLUSIONS: This study found the Borg CR-10 scale to be a reliable and valid
      tool for monitoring the perceived exertion of office exercise training and may
      potentially be useful for occupational therapists to measure physical activity
      intensity levels.

PMID- 30103364
TI  - Dealing with the loss of a resident: An analysis of burnout rates in a reduced
      complement training program.
AB  - BACKGROUND: Residents in all fields of medicine experience high levels of burnout
      and less job-related satisfaction due to the stress experienced during training.
      Reduced complement residency classes often experience increased workloads due to
      the need to compensate for the fewer number of classmates. OBJECTIVE: The goal of
      this study was to examine whether residency classes of reduced size experience
      higher levels of burnout. METHODS: The Maslach Burnout Inventory Survey was
      distributed to all orthopaedic residents at our institution for four consecutive
      years. Emotional exhaustion>=27 and depersonalization>=10 correlate with high
      levels of burnout. At our institution, two residents were lost during their
      second year of training. Group 1 (n = 56) consisted of residents with reduced
      size classes, while group 2 (n = 60) consisted of residents with full complement
      classes. RESULTS: Mean emotional exhaustion (29 vs. 30) and depersonalization (17
      vs. 17) scores were comparable between reduced and full complement classes. The
      Maslach data from our study showed no statistical difference in burnout levels
      between classes of full complement and reduced complement. CONCLUSIONS: When
      compared to a previous study on burnout conducted in large orthopaedic residency
      programs, our entire residency program did demonstrate similar levels of
      emotional exhaustion and depersonalization.

PMID- 30103363
TI  - Evaluation of the effect of psychological recovery tools on back pain in an out
      patient prevention program.
AB  - BACKGROUND: Stress and recovery have recently been linked to health issues and
      back pain (BP) occurrence. However, the evaluation of these aspects in prevention
      programs has not been approached so far. OBJECTIVES: The primary aim of this
      study was to exploratively scrutinize the effectiveness of recovery interventions
      to reduce BP within a multimodal, out-patient prevention program. The secondary
      aim consisted in the evaluation of these recovery interventions in terms of
      reducing stress and increasing recovery. METHODS: A prospective cohort study with
      58 employees was conducted. Thirty-one individuals participated in a multimodal
      out-patient prevention program for 12-weeks, with recovery interventions being
      conveyed as add-ons. The control group did not receive treatment. At baseline
      (T0) and after the prevention program (T1), both groups completed psychometric
      instruments assessing BP, stress, and recovery. RESULTS: A MANOVA indicated that
      Pain Intensity (p = 0.039), Disability (p = 0.011), and Overall Stress (p =
      0.001) were significantly reduced in the intervention group compared to the
      control group. Overall Recovery (p = 0.008) significantly improved in the
      intervention group while deteriorating in the control group. CONCLUSIONS: The
      outcomes emphasize the relevance of recovery tools for BP prevention and for
      reducing stress and enhancing recovery in an out-patient prevention program.

PMID- 30103365
TI  - Factors associated with willingness to work among unemployed persons with a
      disability in a large urban area: A short communication.
AB  - BACKGROUND: One of the reasons for the high unemployment amongst people with
      disability is a lack of knowledge on factors determining their employment.
      Factors associated with willingness and attitudes towards work have not been
      studied sufficiently amongst the general population of people with impaired
      functioning. Recognizing and improving attitudes to work and vocational
      rehabilitation may increase the employment rate of persons with disabilities.
      OBJECTIVE: To investigate the influence of some demographic factors on a
      willingness to work and an interest in vocational rehabilitation amongst
      unemployed persons with confirmed disability. METHODS: Cross-sectional survey
      based study amongst unemployed persons with disabilities in a large urban area.
      The sample consisted of 1 547 respondents with mostly mild or moderate
      disabilities. The multinomial logistic regression was used to obtain relative
      risk ratios (RRs) for different demographic characteristics of the sample.
      RESULTS: An interest in vocational rehabilitation was significantly associated
      with older age (RR 1.36, 95% CI 1.2 to 1.5), lower disability grade (RR 1.30, 95%
      CI 1.06 to 1.60), and lower expectation of a desired salary (RR 0.77, 95% CI 0.67
      to 0.88). Older age (RR 1.31, 95% CI 1.14 to 1.51) and more severe disability
      (reversed figure - RR 0.75, 95% CI 0.60 to 0.93) were associated with a delayed
      willingness to work. CONCLUSIONS: Amongst unemployed persons with severe or
      moderate disabilities, a better willingness to work was mostly associated with
      younger age and milder disability severity. Older persons with less disabilities
      and realistic expectations of salary rate reported an interest in vocational
      rehabilitation more often.

PMID- 30103366
TI  - Experiences of returning to work after brain tumor treatment.
AB  - BACKGROUND: Work participation has a profound influence on the individual's
      overall health and well-being. Cancer survivors are at risk of unemployment, and
      the people with the highest risk are diagnosed with cancer in the central nervous
      system. Many diagnosed with this cancer survive and try to return to a normal
      life including work participation. Experiences related to returning to work after
      brain tumor treatment seem to be an unexplored phenomenon. OBJECTIVE: The current
      study focuses on the gap in the scientific literature concerning the individual
      experience after undergoing treatment for brain cancer and the return to work
      (RTW) process. METHODS: Semi-structured in-depth interviews were conducted with
      four informants, and a thematic content analysis of the transcribed data was
      used. RESULTS: The results show RTW among our informants as a process consists of
      three main themes: easier said than done, from mastering to the feeling of
      inadequacy, and the environment's impact. The categories various components may
      be relevant. CONCLUSION: In a health promotion perspective, several resources
      such as aspects of motivation, self-awareness, and opportunities for facilitation
      and empowerment need to be available in the process of RTW for individuals who
      have undergone treatment for brain cancer.

PMID- 30103367
TI  - Characterization of load reduction while lifting drywall using an unpowered
      drywall lifting device.
AB  - BACKGROUND: Drywall installation has an injury rate four times that of the
      construction industry average. Workers are exposed to hazards related to slips,
      falls, and falling objects, in addition to the large and awkward loads they must
      carry. Drywall sheets can weigh more than 100 lb. and contribute to disabling
      musculoskeletal injuries of the shoulders and back. OBJECTIVE: In this study, an
      unpowered lift assist device was developed to manage the load of a drywall sheet
      during the installation process. METHODS: In order to measure the effect of the
      lift assist device, a laboratory study with 10 healthy male participants
      performing two lifts, lifting from ground to erect and lifting from erect to
      ceiling, with and without the help of the device, was performed. These lifts were
      chosen to simulate a drywall installer's frequent lifting motions. Participants
      were fitted with electromyography (EMG) on the erector spinae, latissimus dorsi,
      rectus abdominus, and external oblique muscles to measure activation. Mean, peak,
      and effort data for the lifting exercises were extracted and compared to the
      unassisted lift. RESULTS: The lift assist device resulted in a reduction in mean
      EMG signal of 69% average over both lifts and muscle groups. Peak EMG and effort
      (i.e., area under the curve) were reduced by 78% and 75%, respectively.
      CONCLUSIONS: These data demonstrate the effectiveness of the device in reducing
      compressive back loads during drywall installation, which warrants future
      development.

PMID- 30103368
TI  - A retrospective study of SPECT/CT scans using SUV measurement of the normal
      pelvis with Tc-99m methylene diphosphonate.
AB  - OBJECTIVE: To perform quantitative measurement based on the standardized uptake
      value (SUV) of Tc-99m methylene diphosphonate (MDP) in the normal pelvis using a
      single-photon emission tomography (SPECT)/computed tomography (CT) scanner.
      MATERIAL AND METHODS: This retrospective study was performed on 31 patients with
      cancer undergoing bone SPECT/CT scans with 99mTc-MDP. SUVmax and SUVmean of the
      normal pelvis were calculated based on the body weight. SUVmax and SUVmean of the
      bilateral anterior superior iliac spine, posterior superior iliac spine, facies
      auricularis ossis ilii, ischial tuberosity, and sacrum were also calculated.
      Furthermore, the correlation of SUVmax and SUVmean of all parts of pelvis with
      weight, height, and CT was assessed. RESULTS: The data for 31 patients (20 women
      and 11 men; mean age 58.97+/-9.12 years; age range 37-87 years) were collected.
      SUVmax and SUVmean changed from 1.65+/-0.40 to 3.8+/-1.0 and from 1.15+/-0.25 to
      2.07+/-0.58, respectively. The coefficient of variation of SUVmax and SUVmean
      ranged from 0.22 to 0.31. SUVmax and SUVmean had no statistically significant
      difference between men and women. SUVmax and SUVmean also showed no significant
      correlation with weight and height. However, part of SUVmax and SUVmean showed a
      significant correlation with CT. In addition, SUVmax and SUVmean of the bilateral
      ischial tuberosity showed a significant correlation with CT values. CONCLUSIONS:
      Determination of the SUV value of the normal pelvis with 99m Tc-MDP SPECT/CT is
      feasible and highly reproducible. SUVs of the normal pelvis showed a relatively
      large variability. As a quantitative imaging biomarker, SUVs might require
      standardization with adequate reference data for the participant to minimize
      variability.

PMID- 30103369
TI  - Can radiological technologists serve as primary screeners of low-dose computed
      tomography for the diagnosis of lung cancer?1.
AB  - BACKGROUND: The Accreditation Council for Lung Cancer CT Screening of Japan
      established guidelines for the certification of Radiological Technologists in
      2009. OBJECTIVE: To analyze the trends in examination pass rates of the
      Radiological Technologists and discuss the reasons. METHODS: The cohort comprised
      1593 Radiological Technologists (as examinees) based on 10-year of data (with a
      total of 17 examination runs). First, the examinees' written test results were
      analyzed. Second, an abnormal finding detection test was conducted using >100
      client PCs connected to a dedicated server containing low-dose lung cancer CT
      screening images of 60 cases. The passing scores were correct answer rate >60%
      and sensitivity (TP) of >90%, respectively. RESULTS: Overall, 1243 examinees
      passed with an overall rate of 78%. The average pass rate for the written test
      was 91%, whereas that for the abnormal findings detection test was 85%. There was
      a moderate correlation between the test pass rate and average years of clinical
      experience of the examinees for the abnormal findings detection test (R = 0.558),
      whereas no such correlation existed for the written test (R = 0.105).
      CONCLUSIONS: In order for accredited Radiological Technologists to serve as
      primary screeners of low-dose computed tomography, it is important to revise the
      educational system according to current standard practices.

PMID- 30103370
TI  - The small animal material discrimination study based on equivalent monochromatic
      energy projection decomposition method with dual-energy CT system.
AB  - Material discrimination is an important application of dual-energy computed
      tomography (CT) techniques. Projection decomposition is a key problem for pre
      reconstruction material discrimination. In this study, we focused on the pre
      reconstruction space based on the photoelectric and Compton effect decomposition
      model to characterize different material components, and proposed an efficient
      method to calculate the projection decomposition coefficient. We converted the
      complex projection integral into a linear equation by calculating the equivalent
      monochromatic energy from the high and low energy spectrum. Meanwhile, we
      constructed a dual-energy CT system based on a photon-counting detector to take
      small animal scan and material discrimination analysis. Finally, the results of
      simulation and experimental study demonstrated the feasibility of our proposed
      new method, and explained the characteristics of photoelectric absorption and
      Compton scattering reconstruction images.

PMID- 30103371
TI  - Performance evaluation of breast cancer diagnosis with mammography,
      ultrasonography and magnetic resonance imaging.
AB  - OBJECTIVE: Various imaging modalities have been used to diagnose suspicious
      breast lesions. Purpose of this study is to compare the diagnostic accuracy for
      breast cancer using mammography, ultrasonography and magnetic resonance imaging
      (MRI). METHODS: Total 107 patients aged from 19 to 62 years are included in this
      retrospective study. Mammography, ultrasonography and MRI scans were performed
      for each patient detected with suspected breast tumor within a month. In
      addition, the tumor diversity (10 types of benign and 5 types of malignant) was
      confirmed by pathological findings of tumor biopsy. To compare the diagnosis
      performance of the three imaging modalities, the overall fraction correct
      (accuracy), positive predict value (PPV), negative predict value (NPV),
      sensitivity and specificity were calculated. Meanwhile, the receiver operating
      characteristic (ROC) analysis was also performed. RESULTS: The diagnostic
      accuracy ranged from 78.5% to 86.9% among three imaging modalities. All
      modalities yielded a PPV lower than 77.8% and a NPV higher than 90.0% in
      identifying the presence of malignant tumors. MRI presented a diagnostic accuracy
      of 86.9%, as well as a sensitivity of 95.5% and an area under curve (AUC) of
      0.948, which are higher than mammography and ultrasonography. CONCLUSION: By
      using a diverse dataset and comparing the diagnostic accuracy of three imaging
      modalities commonly used in breast cancer detection and diagnosis, this study
      also demonstrated that mammography, ultrasonography and MRI had different
      diagnostic performance in breast tumor identification. Among them, MRI yielded
      the highest performance even though the unexpected specificity may lead to over
      diagnosis, and ultrosonography is slightly better than mammography.

PMID- 30103372
TI  - Energy Efficient Management of Pipelines in Buildings Using Linear Wireless
      Sensor Networks.
AB  - The efficient and safe management of air conditioner (AC), Piped Natural Gas
      (PNG) and water pipelines in large buildings is a major challenge for the safety
      of these buildings. In recent years, Linear Wireless Sensor Networks (LWSN) are
      being used extensively for monitoring of long natural gas, water, and oil
      pipelines. LWSNs can also be used for efficient and safe management of AC, PNG
      and water pipelines in large buildings. In this paper, a scheme for optimal
      placement of sensors and base stations in a linear fashion to monitor the various
      pipelines used in large buildings has been proposed. The proposed scheme utilizes
      the Lion Optimization Algorithm (LOA) and has been compared with three
      strategies, namely Ant Colony Optimization (ACO), Genetic Algorithm (GA) and
      Greedy Approach with respect to throughput, lifetime and end-to-end delay. The
      simulation results show that the proposed scheme exhibits better performance in
      comparison to the other three considered techniques for all the three parameters.
      The most striking feature of the proposed approach is that optimization is more
      effective when the length of the pipeline is more as far as end-to-end delay is
      concerned. The lifetime of the network is significantly improved using the
      proposed approach, especially when the length of the pipeline is of medium size,
      which makes the proposed scheme suitable for energy efficient buildings.

PMID- 30103373
TI  - Role of Surfactants in the Properties of Poly(Ethylene Terephthalate)/Purified
      Clay Nanocomposites.
AB  - Purified clay was modified with different amounts of alkyl ammonium and
      phosphonium salts and used as filler in the preparation of PET nanocomposites via
      melt intercalation. The effect of this type of filler on morphology and thermal
      and mechanical properties of PET nanocomposites was investigated by X-ray
      diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric
      analyses (TG), tensile properties, and transmission electron microscopy (TEM).
      The results showed that the mixture of alkyl ammonium and phosphonium salts
      favored the production of PET nanocomposites with intercalated and partially
      exfoliated morphologies with slight improvement in thermal stability. In
      addition, the incorporation of these organoclays tended to inhibit PET
      crystallization behavior, which is profitable in the production of transparent
      bottles.

PMID- 30103375
TI  - Developing and Applying Geographical Synthetic Estimates of Health Literacy in GP
      Clinical Systems.
AB  - Background: Low health literacy is associated with poorer health. Research has
      shown that predictive models of health literacy can be developed; however, key
      variables may be missing from systems where predictive models might be applied,
      such as health service data. This paper describes an approach to developing
      predictive health literacy models using variables common to both "source" health
      literacy data and "target" systems such as health services. Methods: A multilevel
      synthetic estimation was undertaken on a national (England) dataset containing
      health literacy, socio-demographic data and geographical (Lower Super Output
      Area: LSOA) indicators. Predictive models, using variables commonly present in
      health service data, were produced. An algorithm was written to pilot the
      calculations in a Family Physician Clinical System in one inner-city area. The
      minimum data required were age, sex and ethnicity; other missing data were
      imputed using model values. Results: There are 32,845 LSOAs in England, with a
      population aged 16 to 65 years of 34,329,091. The mean proportion of the national
      population below the health literacy threshold in LSOAs was 61.87% (SD 12.26).
      The algorithm was run on the 275,706 adult working-age people in Lambeth, South
      London. The algorithm could be calculated for 228,610 people (82.92%). When
      compared with people for whom there were sufficient data to calculate the risk
      score, people with insufficient data were more likely to be older, male, and
      living in a deprived area, although the strength of these associations was weak.
      Conclusions: Logistic regression using key socio-demographic data and area of
      residence can produce predictive models to calculate individual- and area-level
      risk of low health literacy, but requires high levels of ethnicity recording.
      While the models produced will be specific to the settings in which they are
      developed, it is likely that the method can be applied wherever relevant health
      literacy data are available. Further work is required to assess the feasibility,
      accuracy and acceptability of the method. If feasible, accurate and acceptable,
      this method could identify people requiring additional resources and support in
      areas such as medical practice.

PMID- 30103377
TI  - Perfluoropolyether (PFPE) Intermediate Molds for High-Resolution Thermal
      Nanoimprint Lithography.
AB  - Among soft lithography techniques, Thermal Nanoimprint Lithography (NIL) is a
      high-throughput and low-cost process that can be applied to a broad range of
      thermoplastic materials. By simply applying the appropriate pressure and
      temperature combination, it is possible to transfer a pattern from a mold surface
      to the chosen material. Usually, high-resolution and large-area NIL molds are
      difficult to fabricate and expensive. Furthermore, they are typically made of
      silicon or other hard materials such as nickel or quartz for preserving their
      functionality. Nonetheless, after a large number of imprinting cycles, they
      undergo degradation and become unusable. In this paper, we introduce and
      characterize an innovative two-step NIL process based on the use of a
      perfluoropolyether (PFPE) intermediate mold to replicate sub-100 nm features from
      a silicon mold to the final thermoplastic material. We compare PFPE elastomeric
      molds with molds made of the standard polydimethylsiloxane (PDMS) elastomer,
      which demonstrates better resolution and fidelity of the replica process. By
      using PFPE intermediate molds, the nanostructured masters are preserved and the
      throughput of the process is significantly enhanced.

PMID- 30103376
TI  - Validation of the Apple Watch for Heart Rate Variability Measurements during
      Relax and Mental Stress in Healthy Subjects.
AB  - Heart rate variability (HRV) analysis is a noninvasive tool widely used to assess
      autonomic nervous system state. The market for wearable devices that measure the
      heart rate has grown exponentially, as well as their potential use for healthcare
      and wellbeing applications. Still, there is a lack of validation of these
      devices. In particular, this work aims to validate the Apple Watch in terms of
      HRV derived from the RR interval series provided by the device, both in temporal
      (HRM (mean heart rate), SDNN, RMSSD and pNN50) and frequency (low and high
      frequency powers, LF and HF) domain. For this purpose, a database of 20 healthy
      volunteers subjected to relax and a mild cognitive stress was used. First, RR
      interval series provided by Apple Watch were validated using as reference the RR
      interval series provided by a Polar H7 using Bland-Altman plots and reliability
      and agreement coefficients. Then, HRV parameters derived from both RR interval
      series were compared and their ability to identify autonomic nervous system (ANS)
      response to mild cognitive stress was studied. Apple Watch measurements presented
      very good reliability and agreement (>0.9). RR interval series provided by Apple
      Watch contain gaps due to missing RR interval values (on average, 5 gaps per
      recording, lasting 6.5 s per gap). Temporal HRV indices were not significantly
      affected by the gaps. However, they produced a significant decrease in the LF and
      HF power. Despite these differences, HRV indices derived from the Apple Watch RR
      interval series were able to reflect changes induced by a mild mental stress,
      showing a significant decrease of HF power as well as RMSSD in stress with
      respect to relax, suggesting the potential use of HRV measurements derived from
      Apple Watch for stress monitoring.

PMID- 30103374
TI  - Fusarium graminearum ATP-Binding Cassette Transporter Gene FgABCC9 Is Required
      for Its Transportation of Salicylic Acid, Fungicide Resistance, Mycelial Growth
      and Pathogenicity towards Wheat.
AB  - ATP-binding cassette (ABC) transporters hydrolyze ATP to transport a wide range
      of substrates. Fusarium graminearum is a major causal agent of Fusarium head
      blight, which is a severe disease in wheat worldwide. FgABCC9 (FG05_07325)
      encodes an ABC-C (ABC transporter family C) transporter in F. graminearum, which
      was highly expressed during the infection in wheat and was up-regulated by the
      plant defense hormone salicylic acid (SA) and the fungicide tebuconazole. The
      predicted tertiary structure of the FgABCC9 protein was consistent with the
      schematic of the ABC exporter. Deletion of FgABCC9 resulted in decreased mycelial
      growth, increased sensitivity to SA and tebuconazole, reduced accumulation of
      deoxynivalenol (DON), and less pathogenicity towards wheat. Re-introduction of a
      functional FgABCC9 gene into DeltaFgABCC9 recovered the phenotypes of the wild
      type strain. Transgenic expression of FgABCC9 in Arabidopsis thaliana increased
      the accumulation of SA in its leaves without activating SA signaling, which
      suggests that FgABCC9 functions as an SA exporter. Taken together, FgABCC9
      encodes an ABC exporter, which is critical for fungal exportation of SA, response
      to tebuconazole, mycelial growth, and pathogenicity towards wheat.

PMID- 30103378
TI  - RNA Interference-Mediated Knockdown of Male Fertility Genes in the Queensland
      Fruit Fly Bactrocera tryoni (Diptera: Tephritidae).
AB  - The Queensland fruit fly, Bactrocera tryoni, is Australia's most important
      horticultural pest. The Sterile Insect Technique (SIT) has been used to control
      this species for decades, using radiation to sterilize males before field
      release. This method of sterilization can potentially reduce the insects'
      abilities to compete for mates. In this study, RNA interference (RNAi) techniques
      were examined for their potential to sterilize male B. tryoni without adversely
      affecting mating competitiveness. B. tryoni adults were injected or fed double
      stranded RNAs (dsRNAs) targeting spermatogenesis genes (tssk1, topi and trxt);
      quantitative reverse-transcriptase PCR analyses confirmed that transcript levels
      were reduced 60-80% for all three genes following injections. Feeding produced a
      significant gene knockdown for tssk1 and trxt after three days, but
      interestingly, two genes (trxt and topi) produced an excess of transcripts after
      10 days of feeding. Despite these fluctuations in transcript levels, all three
      dsRNAs impacted the fecundity of treated males, with tssk1- and topi-dsRNA
      treated males producing 75% fewer viable offspring than the negative controls.
      Mating competition assays demonstrated that dsRNA-treated males can actively
      compete with untreated males. These findings suggest that RNAi technology could
      serve as an alternative to radiation as a means of sterilizing these insects in
      an SIT program.

PMID- 30103379
TI  - The Substituent Effect on the Radical Scavenging Activity of Apigenin.
AB  - Flavonoids widely found in natural foods are excellent free radical scavengers.
      The relationship between the substituent and antioxidative activity of flavonoids
      has not yet been completely elucidated. In this work, the antioxidative activity
      of apigenin derivatives with different substituents at the C3 position was
      determined by density functional theory (DFT) calculations. The bond dissociation
      enthalpy (BDE), ionization potential (IP), and proton affinity (PA) were
      calculated. Donator acceptor map (DAM) analysis illustrated that the studied
      compounds are worse electron acceptors than F and also are not better electron
      donors than Na. The strongest antioxidative group of apigenin derivatives was the
      same as apigenin. Excellent correlations were found between the BDE/IP/PA and
      Hammett sigma constants. Therefore, Hammett sigma constants can be used to
      predict the antioxidative activity of substituted apigenin and to design new
      antioxidants based on flavonoids. In non-polar phases, the antioxidative activity
      of apigenin was increased by the electron-withdrawing groups, while it was
      reduced by the electron-donating groups. Contrary results occurred in the polar
      phase. The electronic effect of the substituents on BDE(4'-OH), BDE(5-OH), PA(4'
      OH), and IP is mainly controlled by the resonance effect, while that on BDE(7
      OH), PA(5-OH), and PA(7-OH) is governed by the field/inductive effect.

PMID- 30103380
TI  - Design and Implementation of a Novel Polarimetric Active Radar Calibrator for
      Gaofen-3 SAR.
AB  - The Chinese first fully polarimetric space-borne synthetic aperture radar (SAR)
      Gaofen-3 (GF-3) was launched in August 2016, which operates at the C-band and the
      resolution can reach 1 m. Polarimetric SAR calibration is a procedure that
      corrects the polarization distortion of a measured scattering matrix by referring
      to the scattering matrix of a known target. The present paper describes the
      principle, design, manufacture, and measurement results of a novel polarimetric
      active radar calibrator (PARC) designed for GF-3. A new design method for PARC
      was presented and two dual-polarized antennas with very high polarization purity
      were used. The internal calibration technique was introduced to ensure balance in
      the amplitude and phase, which ensures the precision of the PARC's scattering
      matrices. The results we obtained through measurement in the microwave anechoic
      chamber and experiments in in-orbit calibration agree well with the theoretical
      predictions, and the novel PARC presented is proved to be well suited for
      polarization and radiometric calibration of GF-3.

PMID- 30103381
TI  - The Vestigial Esterase Domain of Haemagglutinin of H5N1 Avian Influenza A Virus:
      Antigenicity and Contribution to Viral Pathogenesis.
AB  - Initial attempts to develop monoclonal antibodies as therapeutics to resolve
      influenza infections focused mainly on searching for antibodies with the
      potential to neutralise the virus in vitro with classical haemagglutination
      inhibition and microneutralisation assays. This led to the identification of many
      antibodies that bind to the head domain of haemagglutinin (HA), which generally
      have potent neutralisation capabilities that block viral entry or viral membrane
      fusion. However, this class of antibodies has a narrow breadth of protection in
      that they are usually strain-specific. This led to the emphasis on stalk
      targeting antibodies, which are able to bind a broad range of viral targets that
      span across different influenza subtypes. Recently, a third class of antibodies
      targeting the vestigial esterase (VE) domain have been characterised. In this
      review, we describe the key features of neutralising VE-targeting antibodies and
      compare them with head- and stalk-class antibodies.

PMID- 30103382
TI  - Molecular Dynamics on Wood-Derived Lignans Analyzed by Intermolecular Network
      Theory.
AB  - The dynamics of interactions to a solvent is a key factor in the proper
      characterization of new molecular structures. In molecular dynamics simulations,
      the solvent molecules are explicitly present, thereby defining a more accurate
      description on how the solvent molecules affect the molecular conformation.
      Intermolecular interactions in chemical systems, e.g., hydrogen bonds, can be
      considered as networks or graphs. Graph theoretical analyses can be an
      outstanding tool in analyzing the changes in interactions between solvent and
      solute. In this study, the software ChemNetworks is applied to interaction
      studies between TIP4P solvent molecules and organic solutes, i.e., wood-derived
      lignan-based ligands called LIGNOLs, thereby supporting the research of
      interaction networks between organic molecules and solvents. This new approach is
      established by careful comparisons to studies using previously available tools.
      In the hydration studies, tetramethyl 1,4-diol is found to be the LIGNOL which
      was most likely to form hydrogen bonds to the TIP4P solvent.

PMID- 30103338
TI  - Reduced Cancer Incidence in Huntington's Disease: Analysis in the Registry Study.
AB  - BACKGROUND: People with Huntington's disease (HD) have been observed to have
      lower rates of cancers. OBJECTIVE: To investigate the relationship between age of
      onset of HD, CAG repeat length, and cancer diagnosis. METHODS: Data were obtained
      from the European Huntington's disease network REGISTRY study for 6540 subjects.
      Population cancer incidence was ascertained from the GLOBOCAN database to obtain
      standardised incidence ratios of cancers in the REGISTRY subjects. RESULTS:
      173/6528 HD REGISTRY subjects had had a cancer diagnosis. The age-standardised
      incidence rate of all cancers in the REGISTRY HD population was 0.26 (CI 0.22
      0.30). Individual cancers showed a lower age-standardised incidence rate compared
      with the control population with prostate and colorectal cancers showing the
      lowest rates. There was no effect of CAG length on the likelihood of cancer, but
      a cancer diagnosis within the last year was associated with a greatly increased
      rate of HD onset (Hazard Ratio 18.94, p < 0.001). CONCLUSIONS: Cancer is less
      common than expected in the HD population, confirming previous reports. However,
      this does not appear to be related to CAG length in HTT. A recent diagnosis of
      cancer increases the risk of HD onset at any age, likely due to increased
      investigation following a cancer diagnosis.

PMID- 30103383
TI  - Impact of Wearing Graduated Compression Stockings on Psychological and
      Physiological Responses during Prolonged Sitting.
AB  - We investigated the impact of wearing vs. not wearing graduated compression
      stockings on psychological and physiological responses in 18 healthy young people
      (12 men and six women) during 3 h prolonged sitting. Profiled of Mood States
      (POMS) scores did not show marked differences between with and without stockings.
      A 3 h sit significantly decreased saliva cortisol in both conditions; with no
      differences between conditions. Wearing stockings suppressed a subjective
      uncomfortable sensation (e.g., pain; fatigue; swelling) in the lower limbs, as
      assessed by visual analogue scale (VAS). Increase in heart rate at 1 h and 3 h
      was significantly greater without than with stockings. In addition, high
      frequency oscillations (HF: 0.15-0.4 Hz), used as an indicator of parasympathetic
      nerve activity, showed higher values with than without stockings throughout the 3
      h sitting period-significantly higher at 1 h. When data for both conditions were
      pooled pre-to-post changes in saliva cortisol were positively associated with
      higher uncomfortable sensations of VAS in the lower limbs and negatively
      associated with changes in the Vigor subscale of POMS. Collectively, these
      findings suggest that wearing graduated compression stockings may benefit from
      subjective comfort and increased parasympathetic nerve activity.

PMID- 30103385
TI  - SPME Method Optimized by Box-Behnken Design for Impact Odorants in Reduced
      Alcohol Wines.
AB  - The important sampling parameters of a headspace solid-phase microextraction-gas
      chromatography-mass spectrometry (HS-SPME-GC-MS) procedure such as the extraction
      temperature, extraction time, and sample volume were optimized to quantify 23
      important impact odorants in reduced alcohol red and white wines. A three-factor
      design of Box-Behnken experiments was used to determine the optimized sampling
      conditions for each analyte, and a global optimized condition at every ethanol
      concentration of interest determined using a desirability function that accounts
      for a low signal response for compounds. Shiraz and Chardonnay wines were
      dealcoholized from 13.7 and 12.2% v/v ethanol respectively, to 8 and 5% v/v,
      using a commercially available membrane-based technology. A sample set of the
      reduced alcohol wines were also reconstituted to their natural ethanol level to
      evaluate the effect of the ethanol content reduction on volatile composition. The
      three-factor Box-Behnken experiment ensured an accurate determination of the
      headspace concentration of each compound at each ethanol concentration, allowing
      comparisons between wines at varying ethanol levels to be made. Overall, the
      results showed that the main effect of extraction temperature was considered the
      most critical factor when studying the equilibrium of reduced alcohol wine impact
      odorants. The impact of ethanol reduction upon the concentration of volatile
      compounds clearly resulted in losses of impact odorants from the wines. The
      concentration of most analytes decreased with dealcoholization compared to that
      of the natural samples. Significant differences were also found between the
      reconstituted volatile composition and 5% v/v reduced alcohol wines, revealing
      that the dealcoholization effect is the result of a combination between the type
      of dealcoholization treatment and reduction in wine ethanol content.

PMID- 30103387
TI  - An Efficient Polymer Inclusion Membrane-Based Device for Cd Monitoring in
      Seawater.
AB  - A novel and simple device that includes a polymer inclusion membrane (PIM) has
      been prepared and tested for the first time to detect low concentration levels of
      cadmium in seawater. The ionic liquid trihexyl (tetradecyl) phosphonium chloride
      (THTDPCl) has been shown to be an effective extractant when incorporated in a PIM
      that uses cellulose triacetate (CTA) as a polymer. However, it has been reported
      that the use of a plasticizer is mandatory to ensure an effective transport,
      which uses both ultrapure water and a nitric acid solution as a stripping phase.
      A special device incorporating a PIM made of 50% CTA, 40% nitrophenyl octyl ether
      (as a plasticizer), and 10% THTDPCl, effectively allows the quantitative
      transport and preconcentration of 10 ug L-1 Cd from seawater samples to a
      stripping phase consisting of 0.5 M HNO3 solution. This study shows that the
      efficiency of the PIM system is not affected by high salinity nor the presence of
      large amounts of other ions, and can thus facilitate Cd monitoring in seawater
      samples.

PMID- 30103386
TI  - Assessment Tools for Health Literacy among the General Population: A Systematic
      Review.
AB  - Health literacy is an important determinant of health, and is one of the key
      indicators of a healthy city. Developing and improving methods to measure health
      literacy is prudent and necessary. This review summarizes the findings of
      published tools for assessing health literacy among the general population to
      provide a reference for establishing health literacy assessment tools in the
      future. In this systematic review, PubMed, Embase, and Web of Science were used
      to search articles regarding tools for assessing health literacy among the
      general population published up to 10 January 2018. Two researchers independently
      conducted literature screening, quality assessment of methodology, and data
      extraction according to preset inclusion and exclusion criteria. The quality
      assessment of the research was examined with the use of the specifications of the
      reporting guidelines for survey research (SURGE). Eleven articles met the
      inclusion criteria. All included instruments in monitoring the health literacy of
      the general population were presented through the form of questionnaires. The
      multistage process of making all the scales generally involved the following
      steps: item development, pre-testing, and evaluation of readability. However, the
      specific methods were different. Internal consistency for all the instruments was
      acceptable but with weak consistency among the subscales for some instruments.
      Most of the identified instruments derived from the definition of health literacy
      or were based on existing health literacy theory. Approximately 30% of the
      performed studies provided no description of the important features specified in
      the SURGE. This review indicates a trend in the increasing tools for assessing
      the health literacy of the general population by using multidimensional
      structures and comprehensive measurement approaches. However, no clear
      "consensus" was observed in the dimensions of health literacy tools.

PMID- 30103388
TI  - Adolescent Finswimmers: Early Myocardial Adaptations in Different Swimming
      Styles.
AB  - BACKGROUND: The purpose of our study was to investigate early differences in the
      adolescent female finswimmers' echocardiography parameters, possibly associated
      with different swimming-style training and different training equipment (monofin
      (MF) versus bifin (BF)). METHOD: Forty-three female finswimmers participated in
      our study (age: 15.6 +/- 2.1 years, body mass index: 20.4 +/- 2.2 kg/m2, body
      surface area: 1.56 +/- 0.04 m2, body fat: 11.2 +/- 0.6%) and were divided into
      two groups, according to the swimming style practiced (MF vs BF). Anthropometric
      characteristics, echocardiography and arterial pressure were measured. The
      independent t-test was used for statistical comparisons between groups. Stepwise
      multivariate regression analysis was applied to investigate associations between
      various variables. RESULTS: The two groups used training equipment with different
      weights (p < 0.001). Female adolescent finswimmers presented signs of myocardial
      hypertrophy depicted by the increased left ventricle myocardial mass indexed to
      body surface area (101.34 +/- 23.65). Different patterns of myocardial
      hypertrophy were observed for the two groups; MF swimmers presented concentric
      hypertrophy, while BF swimmers presented eccentric hypertrophy (relative wall
      thickness MF = 0.46 +/- 0.08 vs BF = 0.39 +/- 0.06 cm, p < 0.05). MF swimmers had
      also higher left ventricular posterior wall diameters (p < 0.05), lower stroke
      volume values (p < 0.05) and lower ejection fraction (p < 0.05) compared to BF
      athletes. CONCLUSION: Adolescent female finswimmers presented different patterns
      of myocardial hypertrophy possibly related to different training protocols and
      modes of exercise.

PMID- 30103384
TI  - Targeting the Microenvironment in High Grade Serous Ovarian Cancer.
AB  - Cancer-stroma interactions play a key role in cancer progression and response to
      standard chemotherapy. Here, we provide a summary of the mechanisms by which the
      major cellular components of the ovarian cancer (OC) tumor microenvironment (TME)
      including cancer-associated fibroblasts (CAFs), myeloid, immune, endothelial, and
      mesothelial cells potentiate cancer progression. High-grade serous ovarian cancer
      (HGSOC) is characterized by a pro-inflammatory and angiogenic signature. This
      profile is correlated with clinical outcomes and can be a target for therapy.
      Accumulation of malignant ascites in the peritoneal cavity allows for secreted
      factors to fuel paracrine and autocrine circuits that augment cancer cell
      proliferation and invasiveness. Adhesion of cancer cells to the mesothelial
      matrix promotes peritoneal tumor dissemination and represents another attractive
      target to prevent metastasis. The immunosuppressed tumor milieu of HGSOC is
      permissive for tumor growth and can be modulated therapeutically. Results of
      emerging preclinical and clinical trials testing TME-modulating therapeutics for
      the treatment of OC are highlighted.

PMID- 30103391
TI  - Future Trend Forecast by Empirical Wavelet Transform and Autoregressive Moving
      Average.
AB  - In engineering and technical fields, a large number of sensors are applied to
      monitor a complex system. A special class of signals are often captured by those
      sensors. Although they often have indirect or indistinct relationships among
      them, they simultaneously reflect the operating states of the whole system. Using
      these signals, the field engineers can evaluate the operational states, even
      predict future behaviors of the monitored system. A novel method of future
      operational trend forecast of a complex system is proposed in this paper. It is
      based on empirical wavelet transform (EWT) and autoregressive moving average
      (ARMA) techniques. Firstly, empirical wavelet transform is used to extract the
      significant mode from each recorded signal, which reflects one aspect of the
      operating system. Secondly, the system states are represented by the indicator
      function which are obtained from those normalized and weighted significant modes.
      Finally, the future trend is forecast by the parametric model of ARMA. The
      effectiveness and practicality of the proposed method are verified by a set of
      numerical experiments.

PMID- 30103390
TI  - Delphinidin Ameliorates Hepatic Triglyceride Accumulation in Human HepG2 Cells,
      but Not in Diet-Induced Obese Mice.
AB  - Anthocyanin consumption is linked to benefits in obesity-related metabolic
      alterations and non-alcoholic fatty liver disease (NAFLD), though the functional
      role of delphinidin (Dp) is yet to be established. Therefore, this study examined
      the effects of Dp on metabolic alterations associated with NAFLD, and molecular
      mechanisms in HepG2 cells and diet-induced obese mice. Cells incubated with
      palmitate to induce lipid accumulation, concomitantly treated with Dp, reduced
      triglyceride accumulation by ~53%, and downregulated gene expression of CPT1A,
      SREBF1, and FASN without modifying AMP-activated protein kinase (AMPK) levels.
      C57BL/6Nhsd mice were fed a standard diet (control) or a high-fat/high
      carbohydrate diet (HFHC) for 16 weeks. Mice in the HFHC group were subdivided and
      treated with Dp (HFHC-Dp, 15 mg/kg body weight/day) or a vehicle for four weeks.
      Dp did not affect body weight, energy intake, hyperglycemia, insulin resistance,
      or histological abnormalities elicited by the HFHC diet. Furthermore, the
      messenger RNA (mRNA) expressions of Acaca, and Fasn in hepatic or epididymal
      adipose tissue, and the hepatic sirtuin 1 (SIRT1)/liver kinase B1 (LKB1)/AMPK and
      proliferator-activated receptor alpha (PPARalpha) signaling axis did not
      significantly change due to the HFHC diet or Dp. In summary, Dp effectively
      reduced triglyceride accumulation in vitro through the modulation of lipid
      metabolic gene expression. However, a dose of Dp administrated in mice simulating
      the total daily anthocyanin intake in humans had no effect on either metabolic
      alterations or histological abnormalities associated with HFHC diets.

PMID- 30103392
TI  - Nest Population Structure and Wood Litter Consumption by Microcerotermes
      indistinctus (Isoptera) in a Seasonally Dry Tropical Forest, Northeastern Brazil.
AB  - Termites are abundant arthropods in tropical ecosystems and actively participate
      in the process of litter decomposition. The objective of this study was to
      evaluate the population structure of Microcerotermes indistinctus in arboreal
      nests and to estimate their contribution to the consumption of wood litter in an
      area of Caatinga, a type of seasonally dry tropical forest located in the
      Brazilian semi-arid region. The populations of fifteen nests were quantified and
      separated into castes, "larvae", and eggs. Wood blocks of four typical Caatinga
      species were offered to termites under laboratory conditions. Litter production
      was estimated in the area over the course of one year. The mean population size
      of M. indistinctus was 73,897 individuals/nest, while the mean nest density in
      the area was 25 active nests/ha. Total consumption of the four types of wood was
      estimated to be 10.5 mg of wood/g termite (fresh weight)/day. Based on
      consumption and population size, M. indistinctus consumes 0.35% of the total
      litter and 1.71% of the annual production of branches and twigs in the area. Wood
      consuming termites are highly affected by anthropogenic disturbances in the semi
      arid region of Brazil, putting the ecosystem services they perform related to the
      process of litter decomposition at risk.

PMID- 30103394
TI  - Towards an Urban Vibrancy Model: A Soundscape Approach.
AB  - Soundscape research needs to develop predictive tools for environmental design. A
      number of descriptor-indicator(s) models have been proposed so far, particularly
      for the "tranquility" dimension to manage "quiet areas" in urban contexts.
      However, there is a current lack of models addressing environments offering
      actively engaging soundscapes, i.e., the "vibrancy" dimension. The main aim of
      this study was to establish a predictive model for a vibrancy descriptor based on
      physical parameters, which could be used by designers and practitioners. A group
      interview was carried out to formulate a hypothesis on what elements would be
      influential for vibrancy perception. Afterwards, data on vibrancy perception were
      collected for different locations in the UK and China through a laboratory
      experiment and their physical parameters were used as indicators to establish a
      predictive model. Such indicators included both aural and visual parameters. The
      model, based on Roughness, Presence of People, Fluctuation Strength, Loudness and
      Presence of Music as predictors, explained 76% of the variance in the mean
      individual vibrancy scores. A statistically significant correlation was found
      between vibrancy scores and eventfulness scores, but not between vibrancy scores
      and pleasantness scores. Overall results showed that vibrancy is contextual and
      depends both on the soundscape and on the visual scenery.

PMID- 30103389
TI  - TGF-Beta Signaling in Bone with Chronic Kidney Disease.
AB  - Transforming growth factor (TGF)-beta signaling is not only important in skeletal
      development, but also essential in bone remodeling in adult bone. The bone
      remodeling process involves integrated cell activities induced by multiple
      stimuli to balance bone resorption and bone formation. TGF-beta plays a role in
      bone remodeling by coordinating cell activities to maintain bone homeostasis.
      However, mineral metabolism disturbance in chronic kidney disease (CKD) results
      in abnormal bone remodeling, which leads to ectopic calcification in CKD. High
      circulating levels of humoral factors such as parathyroid hormone, fibroblast
      growth factor 23, and Wnt inhibitors modulate bone remodeling in CKD. Several
      reports have revealed that TGF-beta is involved in the production and functions
      of these factors in bone. TGF-beta may act as a factor that mediates abnormal
      bone remodeling in CKD.

PMID- 30103393
TI  - Mediterranean Diet and Bladder Cancer Risk in Italy.
AB  - Previous studies have reported that Mediterranean diet is inversely related to
      the risk of several neoplasms; however, limited epidemiological data are
      available for bladder cancer. Thus, we examined the association between
      Mediterranean diet and this neoplasm in an Italian multicentric case-control
      study consisting of 690 bladder cancer cases and 665 controls. We assessed the
      adherence to the Mediterranean diet via a Mediterranean Diet Score (MDS), which
      represents the major characteristics of the Mediterranean diet and ranges from 0
      to 9 (from minimal to maximal adherence, respectively). We derived odds ratios
      (ORs) of bladder cancer according to the MDS score from multiple logistic
      regression models, allowing for major confounding factors. The ORs of bladder
      cancer were 0.72 (95% confidence interval, CI, 0.54-0.98) for MDS of 4-5 and 0.66
      (95% CI, 0.47-0.93) for MDS of 6-9 (p for trend = 0.02) compared to MDS = 0-3.
      Results were similar in strata of sex, age, and education, while the risk
      appeared somewhat lower in never-smokers and patients with pT1-pT4 bladder
      carcinomas. Among individual components of the MDS, we observed inverse
      associations for greater consumption of legumes, vegetables, and fish. In our
      study, which was carried out on an Italian population, the higher adherence to
      the Mediterranean diet was related to a lower risk of bladder cancer.

PMID- 30103396
TI  - Metal Contamination Distribution Detection in High-Voltage Transmission Line
      Insulators by Laser-induced Breakdown Spectroscopy (LIBS).
AB  - The fast detection of classical contaminants and their distribution on high
      voltage transmission line insulators is essential for ensuring the safe operation
      of the power grid. The analysis of existing insulator contamination has
      traditionally relied on taking samples during a power cut, taking the samples
      back to the lab and then testing them with elemental analysis equipment,
      especially for sugars, bird droppings, and heavy metal particulates, which cannot
      be analysed by the equivalent salt deposit density (ESDD) or non-soluble deposit
      density (NSDD) methods. In this study, a novel method called laser-induced
      breakdown spectroscopy (LIBS) offering the advantages of no sample preparation,
      being nearly nondestructive and having a fast speed was applied for the analysis
      of metal contamination. Several LIBS parameters (laser energy and delay time)
      were optimized to obtain better resolution of the spectral data. The limit of
      detection (LOD) of the observed elements was obtained using a calibration curve.
      Compared to calibration curves, multivariate analysis methods including principal
      component analysis (PCA), k-means and partial least squares regression (PLSR)
      showed their superiority in analyzing metal contamination in insulators. Then,
      the elemental distribution of natural pollution was predicted using LIBS to fully
      capture information about the bulk elements (Na, Ni, Cu, Mn, Ca, etc.) of entire
      areas with PLSR. The results showed that LIBS could be a promising method for
      accurate direct online quantification of metal contamination in insulators.

PMID- 30103395
TI  - Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl4-Induced Hepatic
      Fibrosis Animal Model.
AB  - Hepatic fibrosis is the wound-healing process of chronic hepatic disease that
      leads to the end-stage of hepatocellular carcinoma and demolition of hepatic
      structures. Epithelial-mesenchymal transition (EMT) has been identified to
      phenotypic conversion of the epithelium to mesenchymal phenotype that occurred
      during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA
      fragment containing a complementary sequence of Smad transcription factor. Thus,
      this study evaluated the antifibrotic effects of Smad decoy ODN on carbon
      tetrachloride (CCl4)-induced hepatic fibrosis in mice. As shown in histological
      results, CCl4 treatment triggered hepatic fibrosis and increased Smad expression.
      On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT
      process. The expression of Smad signaling and EMT-associated protein was markedly
      decreased in Smad decoy ODN-treated mice compared with CCl4-injured mice. In
      conclusion, these data indicate the practicability of Smad decoy ODN
      administration for preventing hepatic fibrosis and EMT processes.

PMID- 30103397
TI  - High Resolution pH Measurements Using a Lab-on-Chip Sensor in Surface Waters of
      Northwest European Shelf Seas.
AB  - Increasing atmospheric CO2 concentrations are resulting in a reduction in
      seawater pH, with potential detrimental consequences for marine organisms.
      Improved efforts are required to monitor the anthropogenically driven pH decrease
      in the context of natural pH variations. We present here a high resolution
      surface water pH data set obtained in summer 2011 in North West European Shelf
      Seas. The aim of our paper is to demonstrate the successful deployment of the pH
      sensor, and discuss the carbonate chemistry dynamics of surface waters of
      Northwest European Shelf Seas using pH and ancillary data. The pH measurements
      were undertaken using spectrophotometry with a Lab-on-Chip pH sensor connected to
      the underway seawater supply of the ship. The main processes controlling the pH
      distribution along the ship's transect, and their relative importance, were
      determined using a statistical approach. The pH sensor allowed 10 measurements h
      1 with a precision of 0.001 pH units and a good agreement with pH calculated from
      a pair of discretely sampled carbonate variables dissolved inorganic carbon
      (DIC), total alkalinity (TA) and partial pressure of CO2 (pCO2) (e.g.,
      pHDICpCO2). For this summer cruise, the biological activity formed the main
      control on the pH distribution along the cruise transect. This study highlights
      the importance of high quality and high resolution pH measurements for the
      assessment of carbonate chemistry dynamics in marine waters.

PMID- 30103398
TI  - Mechanical and Thermal Performance of Macro-Encapsulated Phase Change Materials
      for Pavement Application.
AB  - Macro-encapsulated phase change material (PCM) lightweight aggregates (ME-LWA)
      were produced and evaluated for their mechanical and thermal properties in road
      engineering applications. The ME-LWAs were first characterised in terms of their
      physical and geometrical properties. Then, the ME-LWAs were investigated in
      detail by applying the European Standards of testing for the Bulk Crushing Test
      and the Polished Stone Value (PSV) coefficient as well as Micro-Deval and
      laboratory profilometry. In addition, the thermal performance for possible
      construction of smart pavements with the inclusion of ME-LWAs for anti-ice
      purposes was determined. The crushing resistance of the ME-LWAs was improved,
      while their resistance to polishing was reduced. Thermal analysis of the
      encapsulated PCM determined it to possess excellent thermal stability and a heat
      storage capacity of 30.43 J/g. Based on the research findings, the inclusion of
      ME-LWAs in surface pavement layers could be considered a viable solution for the
      control of surface temperatures in cold climates. Road safety and maintenance
      could benefit in terms of reduced ice periods and reduced treatments with salts
      and other anti-ice solutions.

PMID- 30103399
TI  - Determinants of Behaviour Change in a Multi-Component Telemonitoring Intervention
      for Community-Dwelling Older Adults.
AB  - Optimal diet quality and physical activity levels are essential for healthy
      ageing. This study evaluated the effects of a multi-component telemonitoring
      intervention on behavioural determinants of diet quality and physical activity in
      older adults, and assessed the mediating role of these determinants and two
      behaviour change techniques in the intervention's effects. A non-randomised
      controlled design was used including 214 participants (average age 80 years) who
      were allocated to the intervention or control group based on municipality. The
      six-month intervention consisted of self-measurements of nutritional outcomes and
      physical activity, education, and follow-up by a nurse. The control group
      received regular care. Measurements took place at baseline, after 4.5 months and
      at the end of the study. The intervention increased self-monitoring and improved
      knowledge and perceived behavioural control for physical activity. Increased self
      monitoring mediated the intervention's effect on diet quality, fruit intake, and
      saturated fatty acids intake. Improved knowledge mediated the effect on protein
      intake. Concluding, this intervention led to improvements in behavioural
      determinants of diet quality and physical activity. The role of the hypothesised
      mediators was limited. Insight into these mechanisms of impact provides
      directions for future development of nutritional eHealth interventions for older
      adults, in which self-monitoring may be a promising behaviour change technique.
      More research is necessary into how behaviour change is established in
      telemonitoring interventions for older adults.

PMID- 30103400
TI  - Nutritional Metabolomics: Postprandial Response of Meals Relating to Vegan, Lacto
      Ovo Vegetarian, and Omnivore Diets.
AB  - Metabolomics provide an unbiased tool for exploring the modulation of the human
      metabolome in response to food intake. This study applied metabolomics to capture
      the postprandial metabolic response to breakfast meals corresponding to vegan
      (VE), lacto ovo-vegetarian (LOV), and omnivore (OM) diets. In a cross over design
      32 healthy volunteers (16 men and 16 females) consumed breakfast meals in a
      randomized order during three consecutive days. Fasting and 3 h postprandial
      serum samples were collected and then subjected to metabolite profiling using 1H
      nuclear magnetic resonance (NMR) spectroscopy. Changes in concentration of
      identified and discriminating metabolites, between fasting and postprandial
      state, were compared across meals. Betaine, choline, and creatine displayed
      higher concentration in the OM breakfast, while 3-hydroxyisobutyrate, carnitine,
      proline, and tyrosine showed an increase for the LOV and unidentified free fatty
      acids displayed a higher concentration after the VE breakfast. Using 1H NMR
      metabolomics it was possible to detect and distinguish the metabolic response of
      three different breakfast meals corresponding to vegan, lacto-ovo vegetarian, and
      omnivore diets in serum.

PMID- 30103401
TI  - Narrative Review of New Methods for Assessing Food and Energy Intake.
AB  - Dietary self-report instruments are essential to nutritional analysis in
      dietetics practice and their use in research settings has facilitated numerous
      important discoveries related to nutrition, health and chronic diseases. An
      important example is obesity, for which measuring changes in energy intake is
      critical for assessing efficacy of dietary interventions. However, current
      methods, including counting calories, estimating portion size and using food
      labels to estimate human energy intake have considerable constraints;
      consequently, research on new methodologies/technologies has been encouraged to
      mitigate the present weaknesses. The use of technologies has prompted innovation
      in dietary analysis. In this review, the strengths and limitations of new
      approaches have been analyzed based on ease of use, practical limitations, and
      statistical evaluation of reliability and validity. Their utility is discussed
      through the lens of the 4Ms of Obesity Assessment and Management, which has been
      used to evaluate root causes of obesity and help select treatment options.

PMID- 30103402
TI  - Evaluation of Alignment between the Health Claims Nutrient Profiling Scoring
      Criterion (NPSC) and the Health Star Rating (HSR) Nutrient Profiling Models.
AB  - In Australia, manufacturers can use two government-endorsed approaches to
      advertise product healthiness: the Health Star Rating (HSR) front-of-pack
      nutrition labelling system, and health claims. Related, but different, algorithms
      determine the star rating of a product (the HSR algorithm) and eligibility to
      display claims (the Nutrient Profiling Scoring Criterion (NPSC) algorithm). The
      objective of this study was to examine the agreement between the HSR and NPSC
      algorithms. Food composition information for 41,297 packaged products was
      extracted from The George Institute's FoodSwitch database. HSR and the NPSC
      scores were calculated, and the proportion of products in each HSR category that
      were eligible to display a health claim under the NPSC was examined. The highest
      agreement between the HSR scoring algorithm and the NPSC threshold to determine
      eligibility to display a health claim was at the HSR cut-off of 3.5 stars (k =
      0.83). Overall, 97.3% (n = 40,167) of products with star ratings of 3.5 or higher
      were also eligible to display a health claim, and 94.3% (n = 38,939) of products
      with star ratings less than 3.5 were ineligible to display a health claim. The
      food group with greatest divergence was "edible oils", with 45% products (n =
      342) with HSR >3.5, but 64% (n = 495) eligible to display a claim. Categories
      with large absolute numbers of products with HSR <3.5, but eligible to display a
      claim, were "yoghurts and yoghurt drinks" (335 products, 25.4%) and "soft drinks"
      (299 products, 29.7%). Categories with a large number of products with HSR >=3.5,
      but ineligible to display a claim, were "milk" (260 products, 21.2%) and "nuts
      and seeds" (173 products, 19.7%). We conclude that there is good agreement
      between the HSR and the NPSC systems overall, but divergence in some food groups
      is likely to result in confusion for consumers, particularly where foods with low
      HSRs are eligible to display a health claim. The alignment of the NPSC and HSR
      scoring algorithms should be improved.

PMID- 30103403
TI  - Ethics and Occupational Health in the Contemporary World of Work.
AB  - The last two decades have seen increasing attention to professional ethics in the
      field of occupational health in industrialized and developing countries, partly
      reflecting the changing world of work, demographic shifts and new technologies.
      These changes have led to the revisiting of traditional ethical principles and
      the emergence of ethical issues related to occupational health. This article
      looks at the problems raised by these ethical concerns and proposes some
      solutions. We revised the existing literature on the ethical conflict in
      occupational health in order to identifying drivers and barriers for correct
      professional ethics. The ethical choices are not only based on balanced risk and
      benefit assessment for various stakeholders, but there are a number of
      deontological aspects as well that go beyond the mere benefit domains. There is
      still no systematic approach for analysing the true extent of these issues and
      their solutions.

PMID- 30103405
TI  - Sustainable Urbanization Performance Evaluation Based on "Origin" and
      "Modernization" Perspectives: A Case Study of Chongqing, China.
AB  - Although the acceleration of urbanization brings social and economic development,
      it also produces various problems. Accurate evaluation of sustainable
      urbanization performance can help local governments summarize experiences and
      solve problems. Sustainable urban development should focus not only on modern
      construction, but also on original natural ecosystems and traditional cultural
      protection. This paper develops a holistic framework based on an "origin" and
      "modernization" perspectives and uses the multilevel extension method and the
      Analytic Hierarchy Process (AHP) method for accurately evaluating sustainable
      urbanization performance. A case study of Chongqing City in China demonstrates
      the process of using the holistic framework and evaluation method. The empirical
      results from this study indicate that Chongqing has a medium level of sustainable
      urbanization. The city is considered as a medium level in "origin" performance
      and the "modernization" performance is good, while uncoordinated. The case study
      reveals that the proposed framework and the method are effective theoretical
      bases for policy-makers and practitioners to understand the performance of urban
      sustainability and for promoting urbanization toward better sustainability.
      Beyond the application case, the holistic framework and method can be applied to
      other cities.

PMID- 30103404
TI  - Pseudopterosin Inhibits Proliferation and 3D Invasion in Triple-Negative Breast
      Cancer by Agonizing Glucocorticoid Receptor Alpha.
AB  - Pseudopterosin, produced by the sea whip of the genus Antillogorgia, possesses a
      variety of promising biological activities, including potent anti-inflammatory
      effects. However, few studies examined pseudopterosin in the treatment of cancer
      cells and, to our knowledge, the ability to inhibit triple-negative breast cancer
      (TNBC) proliferation or invasion has not been explored. Thus, we evaluated the as
      yet unknown mechanism of action of pseudopterosin: Pseudopterosin was able to
      inhibit proliferation of TNBC. Interestingly, analyzing breast cancer cell
      proliferation after knocking down glucocorticoid receptor alpha (GRalpha)
      revealed that the antiproliferative effects of pseudopterosin were significantly
      inhibited when GRalpha expression was reduced. Furthermore, pseudopterosin
      inhibited the invasion of MDA-MB-231 3D tumor spheroids embedded in an
      extracellular-like matrix. Remarkably, the knockdown of GRalpha in 3D tumor
      spheroids revealed increased ability of cells to invade the surrounding matrix.
      In a coculture, encompassing peripheral blood mononuclear cells (PBMC) and MDA-MB
      231 cells, and the production of interleukin 6 (IL-6) and interleukin 8 (IL-8)
      significantly increased compared to a monoculture. Notably, pseudopterosin
      indicated to block cytokine elevation, representing key players in tumor
      progression in the coculture. Thus, our results reveal pseudopterosin treatment
      as a potential novel approach in TNBC therapy.

PMID- 30103406
TI  - Antioxidant Potential of Hemp and Flax Fibers Depending on Their Chemical
      Composition.
AB  - Flax and hemp fibers are known as textile raw materials with pro-health
      properties. This paper presents results of research aimed at investigating the
      antioxidant activity of the fibers in order to explain a mechanism for the
      favorable influence of textiles made of these fibers when in contact with human
      skin. The study presents a new approach in evaluation of textile fibers in terms
      of their inherent pro-health properties. Antioxidant properties of flax and hemp
      fibers were tested with the use of FRAP and DPPH methods. The content of phenolic
      acids: syringic, sinapinic, p-coumaric and ferulic acid was determined with the
      use of HPLC. The results proved that the antioxidant activity of the tested
      fibers depends on a type and variety of fibrous plants, a method of fiber
      extraction and subsequent stages of preliminary processing of the fibers. Both
      decorticated flax and hemp fibers showed higher antioxidant activity in
      comparison to the fibers obtained with other extraction methods, while
      decorticated flax of different varieties presented the highest value of the FRAP.
      Wet methods of fiber extraction and processing caused reduction of phenolic acids
      content and significantly lower values of the FRAP and DPPH.

PMID- 30103408
TI  - Effects of Carbon Source on TiC Particles' Distribution, Tensile, and Abrasive
      Wear Properties of In Situ TiC/Al-Cu Nanocomposites Prepared in the Al-Ti-C
      System.
AB  - The in situ TiC/Al-Cu nanocomposites were fabricated in the Al-Ti-C reaction
      systems with various carbon sources by the combined method of combustion
      synthesis, hot pressing, and hot extrusion. The carbon sources used in this paper
      were the pure C black, hybrid carbon source (50 wt.% C black + 50 wt.% CNTs) and
      pure CNTs. The average sizes of nano-TiC particles range from 67 nm to 239 nm.
      The TiC/Al-Cu nanocomposites fabricated by the hybrid carbon source showed more
      homogenously distributed nano-TiC particles, higher tensile strength and
      hardness, and better abrasive wear resistance than those of the nanocomposites
      fabricated by pure C black and pure CNTs. As the nano-TiC particles content
      increased, the tensile strength, hardness, and the abrasive wear resistance of
      the nanocomposites increased. The 30 vol.% TiC/Al-Cu nanocomposite fabricated by
      the hybrid carbon source showed the highest yield strength (531 MPa), tensile
      strength (656 MPa), hardness (331.2 HV), and the best abrasive wear resistance.

PMID- 30103407
TI  - The Current Role of Salvage Surgery in Recurrent Head and Neck Squamous Cell
      Carcinoma.
AB  - Chemoradiotherapy has emerged as a gold standard in advanced squamous cell
      carcinoma of the head and neck (SCCHN). Because 50% of advanced stage patients
      relapse after nonsurgical primary treatment, the role of salvage surgery (SS) is
      critical because surgery is generally regarded as the best treatment option in
      patients with recurrent resectable SCCHN. Surgeons are increasingly confronted
      with considering operation among patients with significant effects of failed non
      surgical primary treatment. Wide local excision to achieve clear margins must be
      balanced with the morbidity of the procedure, the functional consequences of
      organ mutilation, and the likelihood of success. Accurate selection of patients
      suitable for surgery is a major issue. It is essential to establish objective
      criteria based on functional and oncologic outcomes to select the best candidates
      for SS. The authors propose first to understand preoperative prognostic factors
      influencing survival. Predictive modeling based on preoperative information is
      now available to better select patients having a good chance to be successfully
      treated with surgery. Patients with a high comorbidity index, advanced
      oropharyngeal or hypopharyngeal primary tumors, and both local and regional
      recurrence have a very limited likelihood of success with salvage surgery and
      should be strongly considered for other treatments. Following SS, identifying
      patients with postoperative prognostic factors predicting high risk of recurrence
      is essential because those patients could benefit of adjuvant treatment or be
      included in clinical trials. Finally, defining HPV tumor status is needed in
      future studies including recurrent oropharyngeal SCC patients.

PMID- 30103410
TI  - Microstructure and Mechanical Properties of a Cold-Rolled Ultrafine-Grained Dual
      Phase Steel.
AB  - A new processing route to produce Ultrafine-Grained Dual-Phase steel has been
      proposed, involving cold-rolling and subsequent intercritical annealing of a
      fibrous ferrite-martensite starting structure. Ultrafine-grained DP (UFG-DP)
      steel with an average ferrite grain size of about ~2.7 MUm and an average
      martensite island size of ~2.9 MUm was achieved. Tensile testing revealed
      superior mechanical properties (the ultimate tensile strength of 1267 MPa and
      uniform elongation of 8.2%) for the new DP steel in comparison with the fibrous
      DP steels. The superior mechanical properties are attributed to the influence of
      microstructure refinement on the work-hardening and fracture behavior.

PMID- 30103409
TI  - Phenolic Compounds and Bioactivity of Cytisus villosus Pourr.
AB  - The present study focuses on the chemical composition, antioxidant,
      antimicrobial, and antiproliferative activities of the ethyl acetate and aqueous
      extracts obtained from the aerial parts of Cytisus villosus Pourr. HPLC-DAD
      ESI/MSn was used to identify the phenolic compounds, being (epi)gallocatechin
      dimer the major compound (111 +/- 5 ug/g.dw) in the aqueous extract, while
      myricetin-O-rhamnoside (226 +/- 9 ug/g.dw) was the main molecule in the ethyl
      acetate extract. Both extracts exhibited good scavenging activities against DPPH
      radical (EC50 ug/mL of 59 +/- 2 and 31 +/- 2 for aqueous and ethyl acetate
      extracts, respectively). However, the ethyl acetate extract demonstrated more
      potent quenching activities than the aqueous extract. The antimicrobial
      activities were assessed on selected Gram-positive (Staphylococcus epidermidis)
      and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, as well
      as on pathogenic fungus Candida glabrata. The extracts possessed selective and
      potent antimicrobial activities against the Gram-positive bacterium (IC50 of 186
      +/- 9 MUg/mL and 92 +/- 3 MUg/mL for aqueous and ethyl acetate extracts,
      respectively). Finally, C. villosus extracts were evaluated for their
      antiproliferative potential on three human cancer cell lines representing breast
      and colon cancers. Although both extracts demonstrated sufficient growth
      inhibition of the three different cell lines, the ethyl acetate extract exhibited
      higher activity (LD50 values of 1.57 +/- 0.06 mg/mL, 2.2 +/- 0.1 mg/mL, and 3.2
      +/- 0.2 mg/mL for T47D, MCF-7, and HCT-116 cell lines). Both the extracts
      obtained from the aerial parts of C. villosus revealed very promising results and
      could be applied as functional agents in the food, pharmaceutical, and
      cosmeceutical industries.

PMID- 30103413
TI  - Characterization of Plastidial and Nuclear SSR Markers for Understanding Invasion
      Histories and Genetic Diversity of Schinus molle L.
AB  - Invasive plant species are expected to display high dispersal capacity but low
      levels of genetic diversity due to the founder effect occurring at each invasion
      episode. Understanding the history of invasions and the levels of genetic
      diversity of such species is an important task for planning management and
      monitoring strategy for these events. Peruvian Peppertree (Schinus molle L.) is a
      pioneer tree species native from South America which was introduced in North
      America, Europe and Africa, becoming a threat to these non-native habitats. In
      this study, we report the discovery and characterization of 17 plastidial (ptSSR)
      and seven nuclear (nSSR) markers for S. molle based on low-coverage whole-genome
      sequencing data acquired through next-generation sequencing. The markers were
      tested in 56 individuals from two natural populations sampled in the Brazilian
      Caatinga and Pampa biomes. All loci are moderately to highly polymorphic and
      revealed to be suitable for genetic monitoring of new invasions, for
      understanding the history of old invasions, as well as for genetic studies of
      native populations in their natural occurrence range and of orchards established
      with commercial purposes.

PMID- 30103411
TI  - Murine Bone Marrow Niches from Hematopoietic Stem Cells to B Cells.
AB  - After birth, the development of hematopoietic cells occurs in the bone marrow.
      Hematopoietic differentiation is finely tuned by cell-intrinsic mechanisms and
      lineage-specific transcription factors. However, it is now clear that the bone
      marrow microenvironment plays an essential role in the maintenance of
      hematopoietic stem cells (HSC) and their differentiation into more mature
      lineages. Mesenchymal and endothelial cells contribute to a protective
      microenvironment called hematopoietic niches that secrete specific factors and
      establish a direct contact with developing hematopoietic cells. A number of
      recent studies have addressed in mouse models the specific molecular events that
      are involved in the cellular crosstalk between hematopoietic subsets and their
      niches. This has led to the concept that hematopoietic differentiation and
      commitment towards a given hematopoietic pathway is a dynamic process controlled
      at least partially by the bone marrow microenvironment. In this review, we
      discuss the evolving view of murine hematopoietic-stromal cell crosstalk that is
      involved in HSC maintenance and commitment towards B cell differentiation.

PMID- 30103414
TI  - Intravenous Colistin Monotherapy versus Combination Therapy against Carbapenem
      Resistant Gram-Negative Bacteria Infections: Meta-Analysis of Randomized
      Controlled Trials.
AB  - This meta-analysis aims to compare intravenous colistin monotherapy and colistin
      based combination therapy against carbapenem-resistant gram-negative bacteria
      (GNB) infections. PubMed, Embase, and Cochrane databases were searched up to July
      2018. Only randomized controlled trials (RCTs) evaluating colistin alone and
      colistin-based combination therapy in the treatment of carbapenem-resistant GNB
      infections were included. The primary outcome was all-cause mortality. Five RCTs
      including 791 patients were included. Overall, colistin monotherapy was
      associated with a risk ratio (RR) of 1.03 (95% confidence interval (CI), 0.89
      1.20, I2 = 0%) for all-cause mortality compared with colistin-based combination
      therapy. The non-significant difference was also detected in infection-related
      mortality (RR, 1.23, 95% CI, 0.91-1.67, I2 = 0%) and microbiologic response (RR,
      0.86, 95% CI, 0.72-1.04, I2 = 62%). In addition, no significant difference was
      observed in the subgroup analysis-high or low dose, with or without a loading
      dose, carbapenem-resistant Acinetobacter baumannii infections, and in combination
      with rifampicin. Finally, colistin monotherapy was not associated with lower
      nephrotoxicity than colistin combination therapy (RR, 0.98; 95% CI, 0.84-1.21, I2
      = 0%). Based on the analysis of the five RCTs, no differences were found between
      colistin monotherapy and colistin-based combination therapy against carbapenem
      resistant GNB infections, especially for A. baumannii infections.

PMID- 30103412
TI  - The Methylation Status of the Epigenome: Its Emerging Role in the Regulation of
      Tumor Angiogenesis and Tumor Growth, and Potential for Drug Targeting.
AB  - Approximately 50 years ago, Judah Folkman raised the concept of inhibiting tumor
      angiogenesis for treating solid tumors. The development of anti-angiogenic drugs
      would decrease or even arrest tumor growth by restricting the delivery of oxygen
      and nutrient supplies, while at the same time display minimal toxic side effects
      to healthy tissues. Bevacizumab (Avastin)-a humanized monoclonal anti VEGF-A
      antibody-is now used as anti-angiogenic drug in several forms of cancers, yet
      with variable results. Recent years brought significant progresses in our
      understanding of the role of chromatin remodeling and epigenetic mechanisms in
      the regulation of angiogenesis and tumorigenesis. Many inhibitors of DNA
      methylation as well as of histone methylation, have been successfully tested in
      preclinical studies and some are currently undergoing evaluation in phase I, II
      or III clinical trials, either as cytostatic molecules-reducing the proliferation
      of cancerous cells-or as tumor angiogenesis inhibitors. In this review, we will
      focus on the methylation status of the vascular epigenome, based on the genomic
      DNA methylation patterns with DNA methylation being mainly transcriptionally
      repressive, and lysine/arginine histone post-translational modifications which
      either promote or repress the chromatin transcriptional state. Finally, we
      discuss the potential use of "epidrugs" in efficient control of tumor growth and
      tumor angiogenesis.

PMID- 30103415
TI  - Suppression of Pancreatin-Induced Digestion of Starch in Starch Granules by
      Starch/Fatty Acid and Starch/Flavonoid Complexes in Retrograding Rice Flour.
AB  - Adzuki beans are used to prepare foods with glutinous and non-glutinous rice in
      Japan, and adzuki bean pigments are able to color rice starch a purplish red.
      This study deals with the adzuki bean extract-dependent suppression of starch
      digestion of non-glutinous rice flour (joshinko in Japanese), which was
      gelatinized in boiling water and then cooled to 37  degrees C. Accompanying the
      treatment of joshinko with pancreatin, amylose and amylopectin were released from
      the joshinko particles, and the released amylose and amylopectin were further
      digested. The adzuki extract suppressed the release and digestion by binding to
      amylose and amylopectin, which were present in the particles and at the surfaces
      of the particles. Fatty acids and flavonoids in the adzuki extract contributed to
      the suppression. In addition, the starch digestion in the joshinko particles
      appeared to be suppressed if the amylose/fatty acid complexes and
      amylose/flavonoid and amylopectin/flavonoid complexes, which are poor substrates
      of alpha-amylase, surrounded the particles. It is discussed that the suppression
      was due to the prevention of alpha-amylase access to the particles.

PMID- 30103416
TI  - TiN Films Deposited on Uranium by High Power Pulsed Magnetron Sputtering under
      Low Temperature.
AB  - Depleted uranium (DU) is oxidized readily due to its chemical activities, which
      limits its applications in nuclear industry. TiN film has been applied widely due
      to its good mechanical properties and its excellent corrosion resistance. In this
      work, TiN protection films were deposited on DU by direct current magnetron
      sputtering (DCMS) and high power pulsed magnetron sputtering (HPPMS),
      respectively. The surface morphology and microstructures were investigated by
      atomic force microscope (AFM), scanning electron microscopy (SEM), and grazing
      incidence X-ray diffraction (GIXRD). The hardness and Young's modulus were
      determined by nano-Indenter. The wear behavior and adhesion was analyzed by pin
      on-disc tests and scratch adhesion tests and the corrosion resistance was
      evaluated by electrochemical measurements. The results show that the TiN films
      that were deposited by HPPMS outperformed TiN film deposited by DCMS, with
      improvements on surface roughness, mechanical properties, wear behavior, adhesion
      strength, and corrosion resistance, thanks to its much denser columnar grain
      growth structure and preferred orientation of (111) plane with the lowest strain
      energy. Besides, the process of Ti interlayer deposition by HPPMS can enhance the
      film properties to an extent as compared to DCMS, which is attributed to the
      enhanced ion bombardment during the HPPMS.

PMID- 30103417
TI  - Role of Resultant Dipole Moment in Mechanical Dissociation of Biological
      Complexes.
AB  - Protein-peptide interactions play essential roles in many cellular processes and
      their structural characterization is the major focus of current experimental and
      theoretical research. Two decades ago, it was proposed to employ the steered
      molecular dynamics (SMD) to assess the strength of protein-peptide interactions.
      The idea behind using SMD simulations is that the mechanical stability can be
      used as a promising and an efficient alternative to computationally highly
      demanding estimation of binding affinity. However, mechanical stability defined
      as a peak in force-extension profile depends on the choice of the pulling
      direction. Here we propose an uncommon choice of the pulling direction along
      resultant dipole moment (RDM) vector, which has not been explored in SMD
      simulations so far. Using explicit solvent all-atom MD simulations, we apply SMD
      technique to probe mechanical resistance of ligand-receptor system pulled along
      two different vectors. A novel pulling direction-when ligand unbinds along the
      RDM vector-results in stronger forces compared to commonly used ligand unbinding
      along center of masses vector. Our observation that RDM is one of the factors
      influencing the mechanical stability of protein-peptide complex can be used to
      improve the ranking of binding affinities by using mechanical stability as an
      effective scoring function.

PMID- 30103418
TI  - Enhanced Stretch Formability of AZ31 Magnesium Alloy Thin Sheet by Induced
      Precompression and Sequent Annealing.
AB  - In this study, precompression deformation with a strain level of 5.38% along the
      transverse direction (TD) at room temperature was conducted on a AZ31 magnesium
      alloy thin sheet with thickness of 1mm. Then subsequent annealing treatment was
      carried out at various temperatures (200, 300, 400, and 500  degrees C) to induce
      static recrystallization (SRX) and grain growth. The stretch formability was also
      investigated using the hemispherical test. The results showed that the twinning
      texture induced by the precompression process was nearly inherited by
      recrystallized grains after annealing process. Grains grew up and the size
      increased with the increase of annealing temperature. The largest grain size was
      obtained when annealing at 400  degrees C. The mechanical properties including
      strength and ductility decreased due to the development of coarse grains,
      however, the stretch formability was enhanced significantly. Indeed, the IE-value
      increased from 2.83 mm in the as-received Mg alloy sheet to 5.78 mm in the
      precompressed and 400  degrees C annealed specimens, leading to an improvement of
      104%. This was ascribed to the rotated grain orientation and higher activity of
      (10-12) twins in coarse grains.

PMID- 30103420
TI  - A Nationwide Registry-Based Study on Mortality Due to Rare Congenital Anomalies.
AB  - This study aimed to analyse population-based mortality attributed to rare
      congenital anomalies (CAs) and assess the associated time trends and geographical
      differences in Spain. Data on CA-related deaths were sourced from annual
      mortality databases kept by the National Statistics Institute of Spain (1999
      2013). Based on the ICD-10, only CAs corresponding to rare diseases definition
      were included in this study. Annual age-adjusted mortality rates were calculated
      and time trends were evaluated by joinpoint regression analysis. Geographical
      differences were assessed using standardised mortality ratios and cluster
      detection. A total of 13,660 rare-CA-related deaths (53.4% males) were identified
      in the study period. Annual age-adjusted mortality rates decreased by an average
      of -5.2% (-5.5% males, -4.8% females, p < 0.001). Geographical analysis showed a
      higher risk of rare-CA-related mortality in regions largely located in the south
      of the country. Despite their limitations, mortality statistics are essential and
      useful tools for enhancing knowledge of rare disease epidemiology and, by
      extension, for designing and targeting public health actions. Monitoring rare-CA
      related mortality in Spain has shown a 15-year decline and geographical
      differences in the risk of death, all of which might well be taken into account
      by the health authorities in order to ensure equality and equity, and to adopt
      appropriate preventive measures.

PMID- 30103422
TI  - Estimating Vehicle Movement Direction from Smartphone Accelerometers Using Deep
      Neural Networks.
AB  - Characterization of driving maneuvers or driving styles through motion sensors
      has become a field of great interest. Before now, this characterization used to
      be carried out with signals coming from extra equipment installed inside the
      vehicle, such as On-Board Diagnostic (OBD) devices or sensors in pedals.
      Nowadays, with the evolution and scope of smartphones, these have become the
      devices for recording mobile signals in many driving characterization
      applications. Normally multiple available sensors are used, such as
      accelerometers, gyroscopes, magnetometers or the Global Positioning System (GPS).
      However, using sensors such as GPS increase significantly battery consumption
      and, additionally, many current phones do not include gyroscopes. Therefore, we
      propose the characterization of driving style through only the use of smartphone
      accelerometers. We propose a deep neural network (DNN) architecture that combines
      convolutional and recurrent networks to estimate the vehicle movement direction
      (VMD), which is the forward movement directional vector captured in a phone's
      coordinates. Once VMD is obtained, multiple applications such as characterizing
      driving styles or detecting dangerous events can be developed. In the development
      of the proposed DNN architecture, two different methods are compared. The first
      one is based on the detection and classification of significant acceleration
      driving forces, while the second one relies on longitudinal and transversal
      signals derived from the raw accelerometers. The final success rate of VMD
      estimation for the best method is of 90.07%.

PMID- 30103421
TI  - Synthesis of 2,6-Diamino-Substituted Purine Derivatives and Evaluation of Cell
      Cycle Arrest in Breast and Colorectal Cancer Cells.
AB  - Reversine is a potent antitumor 2,6-diamino-substituted purine acting as an
      Aurora kinases inhibitor and interfering with cancer cell cycle progression. In
      this study we describe three reversine-related molecules, designed by docking
      calculation, that present structural modifications in the diamino units at
      positions 2 and 6. We investigated the conformations of the most stable
      prototropic tautomers of one of these molecules, the N6-cyclohexyl-N6-methyl-N2
      phenyl-7H-purine-2,6-diamine (3), by Density Functional Theory (DFT) calculation
      in the gas phase, water and chloroform, the last solvent considered to give
      insights into the detection of broad signals in NMR analysis. In all cases the
      HN(9) tautomer resulted more stable than the HN(7) form, but the most stable
      conformations changed in different solvents. Molecules 1-3 were evaluated on MCF
      7 breast and HCT116 colorectal cancer cell lines showing that, while being less
      cytotoxic than reversine, they still caused cell cycle arrest in G2/M phase and
      polyploidy. Unlike reversine, which produced a pronounced cell cycle arrest in
      G2/M phase in all the cell lines used, similar concentrations of 1-3 were
      effective only in cells where p53 was deleted or down-regulated. Therefore, our
      findings support a potential selective role of these structurally simplified,
      reversine-related molecules in p53-defective cancer cells.

PMID- 30103419
TI  - Synergistic Integration of Laboratory and Numerical Approaches in Studies of the
      Biomechanics of Diseased Red Blood Cells.
AB  - In red blood cell (RBC) disorders, such as sickle cell disease, hereditary
      spherocytosis, and diabetes, alterations to the size and shape of RBCs due to
      either mutations of RBC proteins or changes to the extracellular environment,
      lead to compromised cell deformability, impaired cell stability, and increased
      propensity to aggregate. Numerous laboratory approaches have been implemented to
      elucidate the pathogenesis of RBC disorders. Concurrently, computational RBC
      models have been developed to simulate the dynamics of RBCs under physiological
      and pathological conditions. In this work, we review recent laboratory and
      computational studies of disordered RBCs. Distinguished from previous reviews, we
      emphasize how experimental techniques and computational modeling can be
      synergically integrated to improve the understanding of the pathophysiology of
      hematological disorders.

PMID- 30103425
TI  - An Accurate Measurement Method for Azimuth Pointing of Spaceborne Synthetic
      Aperture Radar Antenna Beams Based on Ground Receiver.
AB  - The paper proposes a new method for measuring the azimuth pointing of spaceborne
      synthetic aperture radar (SAR) antenna beams based on the ground receiver, which
      can receive and record complex sampling data of the pulse signals transmitted
      from the spaceborne SAR. The center of the antenna pattern is extracted from the
      complex sampling data amplitude envelope to obtain the time when the beam main
      lobe center irradiates the ground receiver, and the range migration information
      is extracted from the complex sampling data to obtain the time when the satellite
      is over the top of the ground receiver. The results of Chinese civilian remote
      sensing GaoFen-3 SAR satellite experiment data processing show that the
      measurement accuracy of this method is better than 0.002 degrees , which can be
      applied to the accurate measurement of azimuth pointing of various low Earth
      orbit (LEO) SAR antenna beams.

PMID- 30103424
TI  - Potential Point-of-Care Microfluidic Devices to Diagnose Iron Deficiency Anemia.
AB  - Over the past 20 years, rapid technological advancement in the field of
      microfluidics has produced a wide array of microfluidic point-of-care (POC)
      diagnostic devices for the healthcare industry. However, potential microfluidic
      applications in the field of nutrition, specifically to diagnose iron deficiency
      anemia (IDA) detection, remain scarce. Iron deficiency anemia is the most common
      form of anemia, which affects billions of people globally, especially the
      elderly, women, and children. This review comprehensively analyzes the current
      diagnosis technologies that address anemia-related IDA-POC microfluidic devices
      in the future. This review briefly highlights various microfluidics devices that
      have the potential to detect IDA and discusses some commercially available
      devices for blood plasma separation mechanisms. Reagent deposition and
      integration into microfluidic devices are also explored. Finally, we discuss the
      challenges of insights into potential portable microfluidic systems, especially
      for remote IDA detection.

PMID- 30103423
TI  - Retinoid X Receptor Antagonists.
AB  - Retinoid X receptor (RXR) antagonists are not only useful as chemical tools for
      biological research, but are also candidate drugs for the treatment of various
      diseases, including diabetes and allergies, although no RXR antagonist has yet
      been approved for clinical use. In this review, we present a brief overview of
      RXR structure, function, and target genes, and describe currently available RXR
      antagonists, their structural classification, and their evaluation, focusing on
      the latest research.

PMID- 30103426
TI  - Accurate Calibration in Multi-Material 3D Bioprinting for Tissue Engineering.
AB  - Most of the studies in three-dimensional (3D) bioprinting have been traditionally
      based on printing a single bioink. Addressing the complexity of organ and tissue
      engineering, however, will require combining multiple building and sacrificial
      biomaterials and several cells types in a single biofabrication session. This is
      a significant challenge, and, to tackle that, we must focus on the complex
      relationships between the printing parameters and the print resolution. In this
      paper, we study the influence of the main parameters driven multi-material 3D
      bioprinting and we present a method to calibrate these systems and control the
      print resolution accurately. Firstly, poloxamer hydrogels were extruded using a
      desktop 3D printer modified to incorporate four microextrusion-based bioprinting
      (MEBB) printheads. The printed hydrogels provided us the particular range of
      printing parameters (mainly printing pressure, deposition speed, and nozzle z
      offset) to assure the correct calibration of the multi-material 3D bioprinter.
      Using the printheads, we demonstrated the excellent performance of the calibrated
      system extruding different fluorescent bioinks. Representative multi-material
      structures were printed in both poloxamer and cell-laden gelatin-alginate bioinks
      in a single session corroborating the capabilities of our system and the
      calibration method. Cell viability was not significantly affected by any of the
      changes proposed. We conclude that our proposal has enormous potential to help
      with advancing in the creation of complex 3D constructs and vascular networks for
      tissue engineering.

PMID- 30103427
TI  - Influenza Virus Infection of Human Lymphocytes Occurs in the Immune Cell Cluster
      of the Developing Antiviral Response.
AB  - Monocytes-macrophages and lymphocytes are recruited to the respiratory tract in
      response to influenza virus challenge and are exposed to the virus during the
      establishment of immune defenses. The susceptibility of human lymphocytes to
      infection was assessed. The presence of monocytes-macrophages was required to
      attain infection of both resting and proliferating lymphocytes. Lymphocyte
      infection occurred in the context of immune cell clusters and was blocked by the
      addition of anti-intercellular adhesion molecule-1 (ICAM-1) antibody to prevent
      cell clustering. Both peripheral blood-derived and bronchoalveolar lymphocytes
      were susceptible to infection. Both CD4+ and CD8+ T lymphocytes were susceptible
      to influenza virus infection, and the infected CD4+ and CD8+ lymphocytes served
      as infectious foci for other nonpermissive or even virus-permissive cells. These
      data show that monocytes-macrophages and both CD4+ and CD8+ lymphocytes can
      become infected during the course of an immune response to influenza virus
      challenge. The described leukocyte interactions during infection may play an
      important role in the development of effective anti-influenza responses.

PMID- 30103430
TI  - Enhanced Antibacterial Activity of Silver Doped Titanium Dioxide-Chitosan
      Composites under Visible Light.
AB  - Nano titanium dioxide (TiO2) with photocatalytic activity was firstly modified by
      diethanolamine, and it was then doped with broad spectrum antibacterial silver
      (Ag) by in situ method. Further, both Ag doped TiO2-chitosan (STC) and TiO2
      chitosan (TC) composites were prepared by the inverse emulsion cross-linking
      reaction. The antibacterial activities of STC composites were studied and their
      antibacterial mechanisms under visible light were investigated. The results show
      that in situ doping and inverse emulsion method led to good dispersion of Ag and
      TiO2 nanoparticles on the cross-linked chitosan microsphere. The STC with regular
      particle size of 1-10 MUm exhibited excellent antibacterial activity against E.
      coli, P. aeruginosa and S. aureus under visible light. It is believed that STC
      with particle size of 1-10 MUm has large specific surface area to contact with
      bacterial cell wall. The increased antibacterial activity was attributed to the
      enhancement of both electron-hole separations at the surface of nano-TiO2 by the
      silver ions under the visible light, and the synergetic and sustained release of
      strong oxidizing hydroxyl radicals of nano-TiO2, together with silver ions
      against bacteria. Thus, STC composites have great potential applications as
      antibacterial agents in the water treatment field.

PMID- 30103429
TI  - Association of Breakfast Quality and Energy Density with Cardiometabolic Risk
      Factors in Overweight/Obese Children: Role of Physical Activity.
AB  - There is a general belief that having breakfast is an important healthy lifestyle
      factor; however, there is scarce evidence on the influence of breakfast quality
      and energy density on cardiometabolic risk in children, as well as on the role of
      physical activity in this association. The aims of this paper were (i) to examine
      the associations of breakfast quality and energy density from both solids and
      beverages with cardiometabolic risk factors, and (ii) to explore whether physical
      activity levels may attenuate these relationships in children with
      overweight/obesity from two projects carried out in the north and south of Spain.
      Breakfast consumption, breakfast quality index (BQI) score, BEDs/BEDb (24 h
      recalls and the KIDMED questionnaire), and physical activity (PA; accelerometry)
      were assessed, in 203 children aged 8-12 years who were overweight or obese. We
      measured body composition (Dual X-ray Absorptiometry), uric acid, blood pressure,
      lipid profile, gamma-glutamyl-transferase (GGT), glucose, and insulin, and
      calculated the HOMA and metabolic syndrome z-score. The BQI score was inversely
      associated with serum uric acid independently of a set of relevant confounders
      (beta = -0.172, p = 0.028), but the relationship was attenuated after further
      controlling for total PA (p < 0.07). BEDs was positively associated with total
      and HDL cholesterol, and systolic blood pressure regardless of confounders (all p
      < 0.05), while BEDb was positively associated with HOMA in either active/inactive
      children (all p < 0.03). In conclusion, higher breakfast quality and lower
      breakfast energy density should be promoted in overweight/obesity children to
      improve their cardiometabolic health.

PMID- 30103428
TI  - The Impact of Vitamin D on the Immunopathophysiology, Disease Activity, and Extra
      Musculoskeletal Manifestations of Systemic Lupus Erythematosus.
AB  - Over the past two decades it has been increasingly recognized that vitamin D,
      aside from its crucial involvement in calcium and phosphate homeostasis and the
      dynamics of the musculoskeletal system, exerts its influential impact on the
      immune system. The mechanistic roles that vitamin D plays regarding immune
      activation for combating infection, as well as pathologically and mediating
      autoimmune conditions, have been progressively unraveled. In vitro and in vivo
      models have demonstrated that the action of vitamin D on various immunocytes is
      not unidirectional. Rather, how vitamin D affects immunocyte functions depends on
      the context of the immune response, in the way that its suppressive or
      stimulatory action offers physiologically appropriate and immunologically
      advantageous outcomes. In this review, the relationship between various aspects
      of vitamin D, starting from its adequacy in circulation to its immunological
      functions, as well as its autoimmune conditions, in particular systemic lupus
      erythematosus (SLE), a prototype autoimmune condition characterized by immune
      complex mediated inflammation, will be discussed. Concurring with other groups of
      investigators, our group found that vitamin D deficiency is highly prevalent in
      patients with SLE. Furthermore, the circulating vitamin D levels appear to be
      correlated with a higher disease activity of SLE as well as extra-musculoskeletal
      complications of SLE such as fatigue, cardiovascular risk, and cognitive
      impairment.

PMID- 30103431
TI  - Salivary Biomarkers of Oxidative Stress in Children with Chronic Kidney Disease.
AB  - There are still missing non-invasive biomarkers of chronic kidney disease (CKD)
      in children. Therefore, the aim of the study was to evaluate oxidative stress
      indicators in the non-stimulated (NWS) and stimulated saliva (SWS) of CKD
      children (n = 25) and healthy controls (n = 25). Salivary antioxidants (catalase
      (CAT), peroxidase (Px), superoxide dismutase (SOD), uric acid (UA), reduced
      glutathione (GSH), albumin), redox status (total antioxidant capacity (TAC),
      total oxidant status (TOS), oxidative stress index (OSI)), and oxidative damage
      products (advanced glycation end products (AGE), advanced oxidation protein
      products (AOPP), malondialdehyde (MDA)) were evaluated. We have demonstrated the
      significantly higher activity of SWS GPx and SOD, as well as elevated
      concentrations of UA and albumin in NWS and SWS of CKD children vs. the control
      group. TAC, TOS and OSI were significantly higher only in SWS, while oxidative
      damage products (AGE, AOPP and MDA) were significantly higher in both NWS and SWS
      of CKD children. ROC analysis showed a considerably high diagnostic value of AOPP
      in both NWS and SWS of CKD children compared to controls (AUC = 0.92; 0.98). CKD
      is responsible for disturbances in salivary antioxidant systems and oxidative
      damage to proteins and lipids. Salivary AOPP can be a potential biomarker of CKD
      in children.

PMID- 30103432
TI  - The Formation of Nanoparticles and Their Competitive Interaction with Twins
      during Eutectic Si Growth.
AB  - In order to investigate the competitive interaction between nanoparticles and
      twin, the eutectic Si microstructures in Al-10Si (wt. %) base alloys with
      exclusive and combined addition of Sr and Sb are characterized by combined TEM
      and atom probe tomography (APT). The chemical short range order in Sb-Sb and Sb
      Sr pairs is revealed by ab initio molecular dynamics simulation, which promotes
      the formation of clusters and nanoparticles. The coexistence of nanoparticles and
      twins is observed in Sb containing alloys, with a negative correlation in the
      corresponding number density, owing to the competitive stacking of precursors and
      individual atoms at the solid-liquid interface. Large size particles around 70 nm
      with a uniform distribution of Sr atoms are formed in Al-10Si-0.35Sb-0.015Sr (wt.
      %) alloys, due to the precursor aggregation and homogeneous nucleation in the
      droplets that nucleation are depressed. A model for the formation of
      nanoparticles and their interaction with twins is proposed.

PMID- 30103433
TI  - Cooperative Data Collection Mechanism Using Multiple Mobile Sinks in Wireless
      Sensor Networks.
AB  - Data collection problems have received much attention in recent years. Many data
      collection algorithms that constructed a path and adopted one or more mobile
      sinks to collect data along the paths have been proposed in wireless sensor
      networks (WSNs). However, the efficiency of the established paths still can be
      improved. This paper proposes a cooperative data collection algorithm (CDCA),
      which aims to prolong the network lifetime of the given WSNs. The CDCA initially
      partitions the n sensor nodes into k groups and assigns each mobile sink acting
      as the local mobile sink to collect data generated by the sensors of each group.
      Then the CDCA selects an appropriate set of data collection points in each group
      and establishes a separate path passing through all the data collection points in
      each group. Finally, a global path is constructed and the rendezvous time points
      and the speed of each mobile sink are arranged for collecting data from k local
      mobile sinks to the global mobile sink. Performance evaluations reveal that the
      proposed CDCA outperforms the related works in terms of rendezvous time, network
      lifetime, fairness index as well as efficiency index.

PMID- 30103436
TI  - Habitat Fragmentation Reduces Genetic Diversity and Connectivity of the Mexican
      Spotted Owl: A Simulation Study Using Empirical Resistance Models.
AB  - We evaluated how differences between two empirical resistance models for the same
      geographic area affected predictions of gene flow processes and genetic diversity
      for the Mexican spotted owl (Strix occidentalis lucida). The two resistance
      models represented the landscape under low- and high-fragmentation parameters.
      Under low fragmentation, the landscape had larger but highly concentrated habitat
      patches, whereas under high fragmentation, the landscape had smaller habitat
      patches that scattered across a broader area. Overall habitat amount differed
      little between resistance models. We tested eight scenarios reflecting a
      factorial design of three factors: resistance model (low vs. high fragmentation),
      isolation hypothesis (isolation-by-distance, IBD, vs. isolation-by-resistance,
      IBR), and dispersal limit of species (200 km vs. 300 km). Higher dispersal limit
      generally had a positive but small influence on genetic diversity. Genetic
      distance increased with both geographic distance and landscape resistance, but
      landscape resistance displayed a stronger influence. Connectivity was positively
      related to genetic diversity under IBR but was less important under IBD.
      Fragmentation had a strong negative influence on the spatial patterns of genetic
      diversity and effective population size (Ns). Despite habitats being more
      concentrated and less widely distributed, the low-fragmentation landscape had
      greater genetic diversity than the high-fragmentation landscape, suggesting that
      highly concentrated but larger habitat patches may provide a genetic refuge for
      the Mexican spotted owl.

PMID- 30103435
TI  - Membrane-Associated Proteins in Giardia lamblia.
AB  - The manner in which membrane-associated proteins interact with the membrane
      defines their subcellular fate and function. This interaction relies on the
      characteristics of the proteins, their journey after synthesis, and their
      interaction with other proteins or enzymes. Understanding these properties may
      help to define the function of a protein and also the role of an organelle. In
      the case of microorganisms like protozoa parasites, it may help to understand
      singular features that will eventually lead to the design of parasite-specific
      drugs. The protozoa parasite Giardia lamblia is an example of a widespread
      parasite that has been infecting humans and animals from ancestral times,
      adjusting itself to the changes of the environment inside and outside the host.
      Several membrane-associated proteins have been posted in the genome database
      GiardiaDB, although only a few of them have been characterized. This review
      discusses the data regarding membrane-associated proteins in relationship with
      lipids and specific organelles and their implication in the discovery of anti
      giardial therapies.

PMID- 30103437
TI  - Reduced Graphene Oxide and Its Modifications as Catalyst Supports and Catalyst
      Layer Modifiers for PEMFC.
AB  - Reduced graphene oxide (RGO) and RGO modified by ozone (RGO-O) and fluorine (RGO
      F) were synthesized. Pt nanoparticles were deposited on these materials and also
      on Vulcan XC-72 using the polyol method. The structural and electrochemical
      properties of the obtained catalysts were investigated in a model glass three
      electrode electrochemical cell and in a laboratory PEM fuel cell. Among the RGO
      based catalysts, the highest electrochemically active surface area (EASA) was
      obtained for the oxidized RGO supported catalyst. The EASA of the fluorine
      modified RGO-supported catalyst was half as big. In the PEM fuel cell the
      performance of RGO-based catalysts did not exceed the activity of Vulcan XC-72
      based catalysts. However, the addition of an RGO-O-based catalyst to Vulcan XC-72
      based catalyst (in contrast to the RGO-F-based catalyst) allowed us to increase
      the catalyst layer activity and PEM fuel cell performance. Possible reasons for
      such an effect are discussed.

PMID- 30103434
TI  - Chemical Synthesis of Rare, Deoxy-Amino Sugars Containing Bacterial
      Glycoconjugates as Potential Vaccine Candidates.
AB  - Bacteria often contain rare deoxy amino sugars which are absent in the host
      cells. This structural difference can be harnessed for the development of
      vaccines. Over the last fifteen years, remarkable progress has been made toward
      the development of novel and efficient protocols for obtaining the rare sugar
      building blocks and their stereoselective assembly to construct conjugation ready
      bacterial glycans. In this review, we discuss the total synthesis of a variety of
      rare sugar containing bacterial glycoconjugates which are potential vaccine
      candidates.

PMID- 30103438
TI  - DPP-IV Inhibitory Potentials of Flavonol Glycosides Isolated from the Seeds of
      Lens culinaris: In Vitro and Molecular Docking Analyses.
AB  - Dipeptidyl peptidase IV (DPP-IV), a new target for the treatment of type 2
      diabetes mellitus, degrades incretins such as glucagon-like peptide 1 (GLP-1) and
      glucose-dependent insulinotropic polypeptide. DPP-IV inhibitors shorten the
      inactivation of GLP-1, permitting the incretin to stimulate insulin release,
      thereby combating hyperglycemia. In our ongoing search for new DPP-IV inhibitors
      from medicinal plants and foods, three flavonol glycosides (1-3) were isolated
      from the seeds of Lens culinaris Medikus (Fabaceae) and tested for their DPP-IV
      inhibitory activity. We demonstrated for the first time, that compounds 1-3
      inhibited DPP-IV activity in a concentration-dependent manner in our in vitro
      bioassay system. In addition, molecular docking experiments of compounds 1-3
      within the binding pocket of DPP-IV were conducted. All investigated compounds
      readily fit within the active sites of DPP-IV, in low-energy conformations
      characterized by the flavone core structure having optimal electrostatic
      attractive interactions with the catalytic triad residues of DPP-IV.

PMID- 30103439
TI  - Perceived Risk, Expected Benefits and Pig Farmers' Behaviors of Veterinary Drug
      Usage.
AB  - To guarantee the pork quality and safety and the steady development of the pig
      breeding industry in China, it is important to control veterinary drugs usage in
      the pig farming sector. In order to develop an effective intervention that
      control veterinary drug usage, it is important to perform an in-depth analysis of
      those factors that can affect the standardized use of veterinary drugs in the pig
      breeding process. In this paper, hierarchical regression analysis is used to
      examine how perceived risk, expected benefits, and self-efficacy influence on the
      standardized use of veterinary drugs. Data were collected using a multi-stage
      sampling method from four provinces in China. The results show that expected
      benefit and self-efficacy have positive impacts on the standardized use of
      veterinary drugs. Self-efficacy significantly moderated the positive
      relationships between expected benefits and the negative relationships between
      perceived risk and standardized use of veterinary drugs.

PMID- 30103440
TI  - A Data Quality Control Method for Seafloor Observatories: The Application of
      Observed Time Series Data in the East China Sea.
AB  - With the construction and deployment of seafloor observatories around the world,
      massive amounts of oceanographic measurement data were gathered and transmitted
      to data centers. The increase in the amount of observed data not only provides
      support for marine scientific research but also raises the requirements for data
      quality control, as scientists must ensure that their research outcomes come from
      high-quality data. In this paper, we first analyzed and defined data quality
      problems occurring in the East China Sea Seafloor Observatory System (ECSSOS). We
      then proposed a method to detect and repair the data quality problems of seafloor
      observatories. Incorporating data statistics and expert knowledge from domain
      specialists, the proposed method consists of three parts: a general pretest to
      preprocess data and provide a router for further processing, data outlier
      detection methods to label suspect data points, and a data interpolation method
      to fill up missing and suspect data. The autoregressive integrated moving average
      (ARIMA) model was improved and applied to seafloor observatory data quality
      control by using a sliding window and cleaning the input modeling data.
      Furthermore, a quality control flag system was also proposed and applied to
      describe data quality control results and processing procedure information. The
      real observed data in ECSSOS were used to implement and test the proposed method.
      The results demonstrated that the proposed method performed effectively at
      detecting and repairing data quality problems for seafloor observatory data.

PMID- 30103441
TI  - Associations between Fatty Acid Intake and Status, Desaturase Activities, and
      FADS Gene Polymorphism in Centrally Obese Postmenopausal Polish Women.
AB  - Fatty acid (FA) status is associated with the risk of several diet-related
      diseases. Since postmenopausal women are at increased risk of cardiometabolic
      disturbances, determinants of FA metabolism should be fully understood in this
      group. We hypothesize that FA metabolism in postmenopausal Polish women may
      depend on current macronutrient intake and on fatty acid desaturase (FADS) gene
      polymorphism. One-hundred-and-twenty-eight postmenopausal women with central
      obesity were recruited to the study and their dietary intake, FA composition in
      red blood cells (RBC), and rs174556, rs174561, rs174547, and rs3834458
      polymorphism of the FADS gene were analyzed. Higher levels of 18:2n-6t level in
      RBC were associated with higher protein or fat intake or with lower carbohydrate
      intake. The minor allele carriers of rs174561 of the fatty acid desaturase 1
      (FADS1) gene had 9.7% lower concentration of 20:4n-6 in RBC (p < 0.05), but there
      were no other associations between other FA in RBC levels and FADS1 or fatty acid
      desaturase 2 (FADS2) polymorphisms. The mean D5D value was 15.3-17.9% lower in
      the minor allele carriers of each SNPs. We concluded that protein and
      carbohydrate intake may be associated with FA concentrations in RBC in centrally
      obese postmenopausal Polish women. The D5D value may be affected by FADS1 or
      FADS2 polymorphism.

PMID- 30103442
TI  - Markers of Oxidative Stress in the Exhaled Breath Condensate of Workers Handling
      Nanocomposites.
AB  - Researchers in nanocomposite processing may inhale a variety of chemical agents,
      including nanoparticles. This study investigated airway oxidative stress status
      in the exhaled breath condensate (EBC). Nineteen employees (42.4 +/- 11.4 y/o),
      working in nanocomposites research for 18.0 +/- 10.3 years were examined pre
      shift and post-shift on a random workday, together with nineteen controls (45.5
      +/- 11.7 y/o). Panels of oxidative stress biomarkers derived from lipids, nucleic
      acids, and proteins were analyzed in the EBC. Aerosol exposures were monitored
      during three major nanoparticle generation operations: smelting and welding
      (workshop 1) and nanocomposite machining (workshop 2) using a suite of real-time
      and integrated instruments. Mass concentrations during these operations were
      0.120, 1.840, and 0.804 mg/m3, respectively. Median particle number
      concentrations were 4.8 * 104, 1.3 * 105, and 5.4 * 105 particles/cm3,
      respectively. Nanoparticles accounted for 95, 40, and 61%, respectively, with
      prevailing Fe and Mn. All markers of nucleic acid and protein oxidation,
      malondialdehyde, and aldehydes C6-C13 were elevated, already in the pre-shift
      samples relative to controls in both workshops. Significant post-shift elevations
      were documented in lipid oxidation markers. Significant associations were found
      between working in nanocomposite synthesis and EBC biomarkers. More research is
      needed to understand the contribution of nanoparticles from nanocomposite
      processing in inducing oxidative stress, relative to other co-exposures generated
      during welding, smelting, and secondary oxidation processes, in these workshops.

PMID- 30103443
TI  - Effect of Bioaugmentation on Biogas Yields and Kinetics in Anaerobic Digestion of
      Sewage Sludge.
AB  - Bioaugmentation with a mixture of microorganisms (Bacteria and Archaea) was
      applied to improve the anaerobic digestion of sewage sludge. The study was
      performed in reactors operating at a temperature of 35  degrees C in semi-flow
      mode. Three runs with different doses of bioaugmenting mixture were conducted.
      Bioaugmentation of sewage sludge improved fermentation and allowed satisfactory
      biogas/methane yields and a biodegradation efficiency of more than 46%, despite
      the decrease in hydraulic retention time (HRT) from 20 d to 16.7 d. Moreover, in
      terms of biogas production, the rate constant k increased from 0.071 h-1 to 0.087
      h-1 as doses of the bioaugmenting mixture were increased, as compared to values
      of 0.066 h-1 and 0.069 h-1 obtained with sewage sludge alone. Next-generation
      sequencing revealed that Cytophaga sp. predominated among Bacteria in digesters
      and that the hydrogenotrophic methanogen Methanoculleus sp. was the most abundant
      genus among Archaea.

PMID- 30103444
TI  - Impact of a Mediterranean Dietary Pattern and Its Components on Cardiovascular
      Risk Factors, Glucose Control, and Body Weight in People with Type 2 Diabetes: A
      Real-Life Study.
AB  - This study evaluates the relation of a Mediterranean dietary pattern and its
      individual components with the cardiovascular risk factors profile, plasma
      glucose and body mass index (BMI) in people with type 2 diabetes. We studied 2568
      participants at 57 diabetes clinics. Diet was assessed with the EPIC (European
      Prospective Investigation into Cancer and Nutrition) questionnaire, adherence to
      the Mediterranean diet was evaluated with the relative Mediterranean diet score
      (rMED). A high compared to a low score was associated with a better quality of
      diet and a greater adherence to the nutritional recommendations for diabetes.
      However, even in the group achieving a high score, only a small proportion of
      participants met the recommendations for fiber and saturated fat (respectively
      17% and 30%). Nonetheless, a high score was associated with lower values of
      plasma lipids, blood pressure, glycated hemoglobin, and BMI. The relationship of
      the single food items components of the rMED score with the achievement of
      treatment targets for plasma lipids, blood pressure, glucose, and BMI were also
      explored. The study findings support the Mediterranean dietary model as a
      suitable model for type 2 diabetes and the concept that the beneficial health
      effects of the Mediterranean diet lie primarily in its synergy among various
      nutrients and foods rather than on any individual component.

PMID- 30103445
TI  - Sequencing of Supernumerary Chromosomes of Red Fox and Raccoon Dog Confirms a Non
      Random Gene Acquisition by B Chromosomes.
AB  - B chromosomes (Bs) represent a variable addition to the main karyotype in some
      lineages of animals and plants. Bs accumulate through non-Mendelian inheritance
      and become widespread in populations. Despite the presence of multiple genes,
      most Bs lack specific phenotypic effects, although their influence on host genome
      epigenetic status and gene expression are recorded. Previously, using sequencing
      of isolated Bs of ruminants and rodents, we demonstrated that Bs originate as
      segmental duplications of specific genomic regions, and subsequently experience
      pseudogenization and repeat accumulation. Here, we used a similar approach to
      characterize Bs of the red fox (Vulpes vulpes L.) and the Chinese raccoon dog
      (Nyctereutes procyonoides procyonoides Gray). We confirm the previous findings of
      the KIT gene on Bs of both species, but demostrate an independent origin of Bs in
      these species, with two reused regions. Comparison of gene ensembles in Bs of
      canids, ruminants, and rodents once again indicates enrichment with cell-cycle
      genes, development-related genes, and genes functioning in the neuron synapse.
      The presence of B-chromosomal copies of genes involved in cell-cycle regulation
      and tissue differentiation may indicate importance of these genes for B
      chromosome establishment.

PMID- 30103446
TI  - Lipidomic Analysis of the Outer Membrane Vesicles from Paired Polymyxin
      Susceptible and -Resistant Klebsiella pneumoniae Clinical Isolates.
AB  - Gram-negative bacteria produce outer membrane vesicles (OMVs) as delivery
      vehicles for nefarious bacterial cargo such as virulence factors, which are
      antibiotic resistance determinants. This study aimed to investigate the impact of
      polymyxin B treatment on the OMV lipidome from paired polymyxin-susceptible and 
      resistant Klebsiella pneumoniae isolates. K. pneumoniae ATCC 700721 was employed
      as a reference strain in addition to two clinical strains, K. pneumoniae FADDI
      KP069 and K. pneumoniae BM3. Polymyxin B treatment of the polymyxin-susceptible
      strains resulted in a marked reduction in the glycerophospholipid, fatty acid,
      lysoglycerophosphate and sphingolipid content of their OMVs. Conversely, the
      polymyxin-resistant strains expressed OMVs richer in all of these lipid species,
      both intrinsically and increasingly under polymyxin treatment. The average
      diameter of the OMVs derived from the K. pneumoniae ATCC 700721 polymyxin
      susceptible isolate, measured by dynamic light scattering measurements, was ~90.6
      nm, whereas the average diameter of the OMVs isolated from the paired polymyxin
      resistant isolate was ~141 nm. Polymyxin B treatment (2 mg/L) of the K.
      pneumoniae ATCC 700721 cells resulted in the production of OMVs with a larger
      average particle size in both the susceptible (average diameter ~124 nm) and
      resistant (average diameter ~154 nm) strains. In light of the above, we
      hypothesize that outer membrane remodelling associated with polymyxin resistance
      in K. pneumoniae may involve fortifying the membrane structure with increased
      glycerophospholipids, fatty acids, lysoglycerophosphates and sphingolipids.
      Putatively, these changes serve to make the outer membrane and OMVs more
      impervious to polymyxin attack.

PMID- 30103449
TI  - Human Polyomaviruses and Papillomaviruses.

PMID- 30103448
TI  - Machine Learning Based Toxicity Prediction: From Chemical Structural Description
      to Transcriptome Analysis.
AB  - Toxicity prediction is very important to public health. Among its many
      applications, toxicity prediction is essential to reduce the cost and labor of a
      drug's preclinical and clinical trials, because a lot of drug evaluations
      (cellular, animal, and clinical) can be spared due to the predicted toxicity. In
      the era of Big Data and artificial intelligence, toxicity prediction can benefit
      from machine learning, which has been widely used in many fields such as natural
      language processing, speech recognition, image recognition, computational
      chemistry, and bioinformatics, with excellent performance. In this article, we
      review machine learning methods that have been applied to toxicity prediction,
      including deep learning, random forests, k-nearest neighbors, and support vector
      machines. We also discuss the input parameter to the machine learning algorithm,
      especially its shift from chemical structural description only to that combined
      with human transcriptome data analysis, which can greatly enhance prediction
      accuracy.

PMID- 30103447
TI  - Myeloid-Derived Suppressor Cells as a Regulator of Immunity in Organ
      Transplantation.
AB  - Regulation of allo-immune responses is proposed as a topic for investigation in
      the current field of organ transplantation. As a regulator, regulatory T cells
      (Tregs) have received attention due to their ability to control allograft
      rejection. Concurrently, however, the independent action of Tregs is not enough
      to achieve tolerance status in many situations. Meanwhile, as a multi-functional
      regulator, myeloid-derived suppressor cells (MDSCs) can suppress effector T cells
      as well as induce Tregs or regulatory B cells (Bregs) in certain circumstances.
      Furthermore, the importance of a crosstalk between MDSCs and natural killer T
      cells to induce tolerance has been reported. Thus, orchestration between MDSCs,
      myeloid regulators, T/Bregs and other lymphoid/myeloid regulators can shed light
      on achieving allogeneic tolerance. Here, we review the current knowledge in terms
      of immunological regulatory function displayed by MDSCs in the context of organ
      transplantation. Ideal control of MDSCs would lead to a reduction of allograft
      rejection and subsequent long-term allograft acceptance.

PMID- 30103452
TI  - Automated Methodology for Dependability Evaluation of Wireless Visual Sensor
      Networks.
AB  - Wireless sensor networks have been considered as an effective solution to a wide
      range of applications due to their prominent characteristics concerning
      information retrieving and distributed processing. When visual information can be
      also retrieved by sensor nodes, applications acquire a more comprehensive
      perception of monitored environments, fostering the creation of wireless visual
      sensor networks. As such networks are being more often considered for critical
      monitoring and control applications, usually related to catastrophic situation
      prevention, security enhancement and crises management, fault tolerance becomes a
      major expected service for visual sensor networks. A way to address this issue is
      to evaluate the system dependability through quantitative attributes (e.g.,
      reliability and availability), which require a proper modeling strategy to
      describe the system behavior. That way, in this paper, we propose a methodology
      to model and evaluate the dependability of wireless visual sensor networks using
      Fault Tree Analysis and Markov Chains. The proposed modeling strategy considers
      hardware, battery, link and coverage failures, besides considering routing
      protocols on the network communication behavior. The methodology is automated by
      a framework developed and integrated with the SHARPE (Symbolic Hierarchical
      Automated Reliability and Performance Evaluator) tool. The achieved results show
      that this methodology is useful to compare different network implementations and
      the corresponding dependability, enabling the uncovering of potentially weak
      points in the network behavior.

PMID- 30103450
TI  - Non-Coding Transcriptome Maps across Twenty Tissues of the Korean Black Chicken,
      Yeonsan Ogye.
AB  - Yeonsan Ogye is a rare Korean domestic chicken breed whose entire body, including
      feathers and skin, has a unique black coloring. Although some protein-coding
      genes related to this unique feature have been examined, non-coding elements have
      not been widely investigated. Thus, we evaluated coding and non-coding
      transcriptome expression and identified long non-coding RNAs functionally linked
      to protein-coding genes in Ogye. High-throughput RNA sequencing and DNA
      methylation sequencing were performed to profile the expression of 14,264 Ogye
      protein-coding and 6900 long non-coding RNA (lncRNA) genes and detect DNA
      methylation in 20 different tissues of an individual Ogye. Approximately 75% of
      Ogye lncRNAs and 45% of protein-coding genes showed tissue-specific expression.
      For some genes, tissue-specific expression levels were inversely correlated with
      DNA methylation levels in their promoters. Approximately 39% of tissue-specific
      lncRNAs displayed functional associations with proximal or distal protein-coding
      genes. Heat shock transcription factor 2-associated lncRNAs appeared to be
      functionally linked to protein-coding genes specifically expressed in black skin
      tissues, more syntenically conserved in mammals, and differentially expressed in
      black relative to in white tissues. Pending experimental validation, our findings
      increase the understanding of how the non-coding genome regulates unique
      phenotypes and can be used for future genomic breeding of chickens.

PMID- 30103451
TI  - Phytochemicals in Helicobacter pylori Infections: What Are We Doing Now?
AB  - In this critical review, plant sources used as effective antibacterial agents
      against Helicobacter pylori infections are carefully described. The main
      intrinsic bioactive molecules, responsible for the observed effects are also
      underlined and their corresponding modes of action specifically highlighted. In
      addition to traditional uses as herbal remedies, in vitro and in vivo studies
      focusing on plant extracts and isolated bioactive compounds with anti-H. pylori
      activity are also critically discussed. Lastly, special attention was also given
      to plant extracts with urease inhibitory effects, with emphasis on involved modes
      of action.

PMID- 30103454
TI  - A Novel Multiattribute Decision-Making Method Based on Point-Choquet Aggregation
      Operators and Its Application in Supporting the Hierarchical Medical Treatment
      System in China.
AB  - The hierarchical medical treatment system is an efficient way to solve the
      problem of insufficient and unbalanced medical resources in China. Essentially,
      classifying the different degrees of diseases according to the doctor's diagnosis
      is a key step in pushing forward the hierarchical medical treatment system. This
      paper proposes a framework to solve the problem where diagnosis values are given
      as picture fuzzy numbers (PFNs). Point operators can reduce the uncertainty of
      doctor's diagnosis and get intensive information in the process of decision
      making, and the Choquet integral operator can consider correlations among
      symptoms. In order to take full advantage of these two kinds of operators, in
      this paper, we firstly define some point operators under the picture fuzzy
      environment, and further propose a new class of picture fuzzy point-Choquet
      integral aggregation operators. Moreover, some desirable properties of these
      operators are also investigated in detail. Then, a novel approach based on these
      operators for multiattribute decision-making problems in the picture fuzzy
      context is introduced. Finally, we give an example to illustrate the
      applicability of the new approach in assisting hierarchical medical treatment
      system. This is of great significance for integrating the medical resources of
      the whole society and improving the service efficiency of the medical service
      system.

PMID- 30103455
TI  - Nitrogen Supply and Leaf Age Affect the Expression of TaGS1 or TaGS2 Driven by a
      Constitutive Promoter in Transgenic Tobacco.
AB  - Glutamine synthetase (GS) plays a key role in nitrogen metabolism. Here, two
      types of tobacco transformants, overexpressing Triticum aestivum GS1 (TaGS1) or
      GS2 (TaGS2), were analysed. Four independent transformed lines, GS1-TR1, GS1-TR2,
      GS2-TR1 and GS2-TR2, were used for the nitrogen treatment. Under nitrogen
      sufficient conditions, the leaves of GS2-TR showed high accumulation of the TaGS2
      transcript, while those of GS1-TR showed a low TaGS1 transcript levels. However,
      compared with nitrogen-sufficient conditions, the TaGS1 transcript level
      increased in the leaves under nitrogen starvation, but the TaGS2 transcript level
      decreased. In addition, the TaGS1 and TaGS2 transcript levels were highest in the
      middle leaves under nitrogen-sufficient and starvation conditions. These results
      show that nitrogen supply and leaf age regulate TaGS expression, even when they
      are driven by a super-promoter. Additionally, in regard to nitrogen metabolism
      level, the lower leaves of the GS1-TR exhibited lower NH4+ and higher amino acid
      contents, while the upper leaves exhibited higher amino acid, soluble protein and
      chlorophyll contents. The leaves of the GS2-TR exhibited lower NH4+ but higher
      amino acid, soluble protein and chlorophyll contents. Given the role that GS
      isoforms play in nitrogen metabolism, these data suggest that TaGS1
      overexpression may improve nitrogen transport, and that TaGS2 overexpression may
      improve nitrogen assimilation under nitrogen stress.

PMID- 30103456
TI  - Comparing the Normalized Difference Vegetation Index with the Google Street View
      Measure of Vegetation to Assess Associations between Greenness, Walkability,
      Recreational Physical Activity, and Health in Ottawa, Canada.
AB  - The manner in which features of the built environment, such as walkability and
      greenness, impact participation in recreational activities and health are
      complex. We analyzed survey data provided by 282 Ottawa adults in 2016. The
      survey collected information on participation in recreational physical activities
      by season, and whether these activities were performed within participants'
      neighbourhoods. The SF-12 instrument was used to characterize their overall
      mental and physical health. Measures of active living environment, and the
      satellite derived Normalized Difference Vegetation Index (NDVI) and Google Street
      View (GSV) greenness indices were assigned to participants' residential
      addresses. Logistic regression and least squares regression were used to
      characterize associations between these measures and recreational physical
      activity, and self-reported health. The NDVI was not associated with
      participation in recreational activities in either the winter or summer, or
      physical or mental health. In contrast, the GSV was positively associated with
      participation in recreational activities during the summer. Specifically, those
      in the highest quartile spent, on average, 5.4 more hours weekly on recreational
      physical activities relative to those in the lowest quartile (p = 0.01). Active
      living environments were associated with increased utilitarian walking, and
      reduced reliance on use of motor vehicles. Our findings provide support for the
      hypothesis that neighbourhood greenness may play an important role in promoting
      participation in recreational physical activity during the summer.

PMID- 30103453
TI  - Melatonin Uptake by Cells: An Answer to Its Relationship with Glucose?
AB  - Melatonin, N-acetyl-5-methoxytryptamine, is an indole mainly synthesized from
      tryptophan in the pineal gland and secreted exclusively during the night in all
      the animals reported to date. While the pineal gland is the major source
      responsible for this night rise, it is not at all the exclusive production site
      and many other tissues and organs produce melatonin as well. Likewise, melatonin
      is not restricted to vertebrates, as its presence has been reported in almost all
      the phyla from protozoa to mammals. Melatonin displays a large set of functions
      including adaptation to light: dark cycles, free radical scavenging ability,
      antioxidant enzyme modulation, immunomodulatory actions or differentiation
      proliferation regulatory effects, among others. However, in addition to those
      important functions, this evolutionary 'ancient' molecule still hides further
      tools with important cellular implications. The major goal of the present review
      is to discuss the data and experiments that have addressed the relationship
      between the indole and glucose. Classically, the pineal gland and a pinealectomy
      were associated with glucose homeostasis even before melatonin was chemically
      isolated. Numerous reports have provided the molecular components underlying the
      regulatory actions of melatonin on insulin secretion in pancreatic beta-cells,
      mainly involving membrane receptors MTNR1A/B, which would be partially
      responsible for the circadian rhythmicity of insulin in the organism. More
      recently, a new line of evidence has shown that glucose transporters GLUT/SLC2A
      are linked to melatonin uptake and its cellular internalization. Beside its
      binding to membrane receptors, melatonin transportation into the cytoplasm,
      required for its free radical scavenging abilities, still generates a great deal
      of debate. Thus, GLUT transporters might constitute at least one of the keys to
      explain the relationship between glucose and melatonin. These and other potential
      mechanisms responsible for such interaction are also discussed here.

PMID- 30103457
TI  - Early Investigations and Recent Advances in Intraperitoneal Immunotherapy for
      Peritoneal Metastasis.
AB  - Peritoneal metastasis (PM) is an advanced stage malignancy largely refractory to
      modern therapy. Intraperitoneal (IP) immunotherapy offers a novel approach for
      the control of regional disease of the peritoneal cavity by breaking immune
      tolerance. These strategies include heightening T-cell response and vaccine
      induction of anti-cancer memory against tumor-associated antigens. Early
      investigations with chimeric antigen receptor T cells (CAR-T cells), vaccine
      based therapies, dendritic cells (DCs) in combination with pro-inflammatory
      cytokines and natural killer cells (NKs), adoptive cell transfer, and immune
      checkpoint inhibitors represent significant advances in the treatment of PM. IP
      delivery of CAR-T cells has shown demonstrable suppression of tumors expressing
      carcinoembryonic antigen. This response was enhanced when IP injected CAR-T cells
      were combined with anti-PD-L1 or anti-Gr1. Similarly, CAR-T cells against folate
      receptor alpha expressing tumors improved T-cell tumor localization and survival
      when combined with CD137 co-stimulatory signaling. Moreover, IP immunotherapy
      with catumaxomab, a trifunctional antibody approved in Europe, targets epithelial
      cell adhesion molecule (EpCAM) and has shown considerable promise with control of
      malignant ascites. Herein, we discuss immunologic approaches under investigation
      for treatment of PM.

PMID- 30103459
TI  - Prescribing Empiric Antibiotics for Febrile Neutropenia: Compliance with
      Institutional Febrile Neutropenia Guidelines.
AB  - Background: Febrile neutropenia (FN) is an oncologic emergency which should be
      treated immediately with empiric antibiotics. Different institutions observe
      different antibiograms and use different FN management guidelines. Our center
      implemented FN management guidelines for adult cancer patients in 2009. Hence, we
      decided to assess compliance with FN management guidelines and to describe the
      pattern of bacterial infections. Method: We conducted a cross-sectional study on
      all adult cancer patients admitted with FN. Data were collected from electronic
      medical records between January and December 2014. Results: One hundred FN
      episodes met the study inclusion criteria. The mean age of the patients was 41 +/
      17 years; 52% (52 patients) were women. The most common diagnosis was lymphoma
      (33%). In terms of compliance to institutional FN guidelines, 55% of patients
      received guideline non-compliant treatment. The most common non-compliant
      treatment was incorrect amikacin dosing in 31% of patients, followed by incorrect
      vancomycin dosing in 20%, incorrect piperacillin/tazobactam dosing in 19%,
      inappropriate use of carbapenems in 18%, and non-compliant vancomycin use in 12%
      of patients. Bacterial isolates were only observed in 19% of the FN episodes.
      Among these 19 episodes of FN, Gram-negative pathogens were predominant and were
      identified in 74% of the episodes, followed by Gram-positive pathogens in 16% and
      polymicrobial pathogens in 10%. The mean time to defervescence was 2.21 +/- 2
      days. Conclusion: Our study concluded that there was a high percentage of non
      compliance with our institutional FN management guidelines. We recommend
      following appropriate empiric antibiotic doses and indications as per
      institutional guidelines.

PMID- 30103460
TI  - TLTD: A Testing Framework for Learning-Based IoT Traffic Detection Systems.
AB  - With the popularization of IoT (Internet of Things) devices and the continuous
      development of machine learning algorithms, learning-based IoT malicious traffic
      detection technologies have gradually matured. However, learning-based IoT
      traffic detection models are usually very vulnerable to adversarial samples.
      There is a great need for an automated testing framework to help security
      analysts to detect errors in learning-based IoT traffic detection systems. At
      present, most methods for generating adversarial samples require training
      parameters of known models and are only applicable to image data. To address the
      challenge, we propose a testing framework for learning-based IoT traffic
      detection systems, TLTD. By introducing genetic algorithms and some technical
      improvements, TLTD can generate adversarial samples for IoT traffic detection
      systems and can perform a black-box test on the systems.

PMID- 30103458
TI  - Identifying Phage Virion Proteins by Using Two-Step Feature Selection Methods.
AB  - Accurate identification of phage virion protein is not only a key step for
      understanding the function of the phage virion protein but also helpful for
      further understanding the lysis mechanism of the bacterial cell. Since
      traditional experimental methods are time-consuming and costly for identifying
      phage virion proteins, it is extremely urgent to apply machine learning methods
      to accurately and efficiently identify phage virion proteins. In this work, a
      support vector machine (SVM) based method was proposed by mixing multiple sets of
      optimal g-gap dipeptide compositions. The analysis of variance (ANOVA) and the
      minimal-redundancy-maximal-relevance (mRMR) with an increment feature selection
      (IFS) were applied to single out the optimal feature set. In the five-fold cross
      validation test, the proposed method achieved an overall accuracy of 87.95%. We
      believe that the proposed method will become an efficient and powerful method for
      scientists concerning phage virion proteins.

PMID- 30103461
TI  - Identification of Factors Associated with Potential Doping Behavior in Sports: A
      Cross-Sectional Analysis in High-Level Competitive Swimmers.
AB  - Background: Doping behavior, including the misuse of performance-enhancing drugs,
      is currently a serious problem in sports, and the efficacy of preventive efforts
      directly depends on information regarding the associations among different
      precipitating factors (PF) and doping behavior. This study aimed to establish the
      PF of potential doping behavior (PDB) in competitive swimmers. Methods: The study
      included 301 swimmers from Slovenia (153 females, 16.4 +/- 2.4 years), tested
      during the 2017 National Championship. Variables were collected by previously
      validated questionnaires, which included questions on sociodemographics, sports
      related factors, consumption of dietary supplements, knowledge of doping, factors
      of hesitation, and doping-related factors (i.e., number of doping tests, opinion
      about the presence of doping in sport). The PDB (positive, neutral, or negative
      intention toward doping) was observed as a criterion, while other variables were
      included as predictors in multinomial regression analyses (with "negative" as
      reference value), which additionally controlled for gender and age category
      (cadet-, junior-, and senior-level) as confounders. Results: The results
      confirmed higher susceptibility to doping in males (positive: odds ratio (OR):
      2.77, 95% confidence interval (CI): 1.27-6.04), those swimmers who reported
      higher alcohol consumption (neutral: OR: 2.18, 95%CI: 1.06-4.16, positive: OR:
      2.14, 95%CI: 1.05-4.37), and those regularly used dietary supplements (positive:
      OR: 3.62, 95%CI: 1.25-10.52). Competitive achievement in Olympic- (neutral: OR:
      0.57, 95%CI: 0.41-0.81, positive: OR: 0.59, 95%CI: 0.39-0.88), and non-Olympic
      disciplines (positive: OR: 0.54, 95%CI: 0.35-0.83) was protective against PDB.
      Swimmers who were more concerned about the negative social consequences of doping
      behavior (i.e., condemnation by family and friends) were less likely to declare a
      positive intention toward the PDB (family condemnation: OR: 0.69, 95%CI: 0.56
      0.86, friends' condemnation: OR: 0.65, 95%CI: 0.52-0.80). Conclusions: The
      results of the study provide more precise insight into the specific factors
      associated with PDB in swimming. The established precipitating factors should be
      incorporated into targeted anti-doping campaigns in this sport.

PMID- 30103463
TI  - Circumstances and Structure of Occupational Sharp Injuries among Healthcare
      Workers of a Selected Hospital in Central Poland.
AB  - : (1) Background: An analysis of work-related sharp injuries in Healthcare
      Workers (HCWs) based at a selected hospital in Central Poland by presenting the
      frequency of accidents, injury rates, and identifying circumstances of Needle
      Sticks and Sharp Injuries (NSSI) and giving Post-Exposure Procedures (PEP). (2)
      Methods: A retrospective analysis of medical documentation regarding work-related
      NSSI at a district hospital located in central Poland; over the period 2010-2017.
      The study group included HCWs who had an accident while on duty. (3) Results:
      Most injuries were reported by nurses and staff over 40, on the morning shift.
      The most common injuries were using a needle. The most exposed part of the body
      were fingers. The average annual injury rates were: 1.22/100 Nurses; 2.02/100
      doctors; 1.34/100 hospital beds; and 8.59/100,000 inpatient days. The rates for 3
      year periods, after the implementation of legal regulations were higher than
      before. CONCLUSION: Injuries rates are more reliable for comparison than
      frequency. Legislation on the need to register injuries seems to be necessary. In
      the supervision of work safety of personnel, reliable reporting of all injuries
      by the respective HCWs plays a key role.

PMID- 30103462
TI  - The Effect of Absorption-Enhancement and the Mechanism of the PAMAM Dendrimer on
      Poorly Absorbable Drugs.
AB  - The polyamidoamine (PAMAM) dendrimer is a highly efficient absorption promoter.
      In the present study, we studied the absorption-enhancing effects and the
      mechanism of PAMAM dendrimers with generation 0 to generation 3 (G0-G3) and
      concentrations (0.1-1.0%) on the pulmonary absorption of macromolecules. The
      absorption-enhancing mechanisms were elucidated by microarray, western blotting
      analysis, and PCR. Fluorescein isothiocyanate-labeled dextrans (FDs) with various
      molecular weights were used as model drugs of poorly absorbable drugs. The
      absorption-enhancing effects of PAMAM dendrimers on the pulmonary absorption of
      FDs were in a generation- and concentration-dependent manner. The G3 PAMAM
      dendrimer with high effectiveness was considered to the best absorption enhancer
      for improving the pulmonary absorption of FDs. G3 PAMAM dendrimers at three
      different concentrations were non-toxic to Calu-3 cells. Based on the
      consideration between efficacy and cost, the 0.1% G3 PAMAM dendrimer was selected
      for subsequent studies. The results showed that treatment with a 0.1% G3 PAMAM
      dendrimer could increase the secretion of organic cation transporters (OCTs),
      OCT1, OCT2, and OCT3, which might be related to the absorption-enhancing
      mechanisms of the pulmonary absorption of FDs. These findings suggested that
      PAMAM dendrimers might be potentially safe absorption enhancers for improving
      absorption of FDs by increasing the secretion of OCT1, OCT2, and OCT3.

PMID- 30103464
TI  - Caffeinated Drinks Intake, Late Chronotype, and Increased Body Mass Index among
      Medical Students in Chongqing, China: A Multiple Mediation Model.
AB  - Background: This paper investigates the problems regarding caffeinated drinks
      intake, late chronotype, and increased body mass index (BMI) among medical
      students at a Chinese university. Methods: This cross-sectional study was
      conducted in 2018 with 616 medical students from Chongqing Medical University in
      Chongqing, China, whose information were collected by a self-reported
      questionnaire that included four sections: Demographic characteristics;
      Caffeinated drinks intake and physical state; Morningness-Eveningness
      Questionnaire; Depression Anxiety Stress Scale 21. Multiple mediation analyses
      were conducted to test the impact of late chronotype on increased BMI through
      caffeinated drinks consumption through two models. Results: The significantly
      mediated effect of caffeinated drinks consumption was revealed (estimate: -0.01,
      SE = 0.01, 95% CI [-0.02, -0.01]), and which played a positive role in linking
      late chronotype (B = -0.01, SE = 0.01, p < 0.001) and increased BMI (B = 1.37, SE
      = 0.21, p < 0.01), but their significant association did not be found in reversed
      model. In addition, physical activity and inactivity times demonstrated
      significant indirect effects in the two models. Conclusions: Interventions should
      focus on reducing caffeinated drinks intake and sedentary behavior time,
      enhancing physical activity among medical students.

PMID- 30103465
TI  - Fragment-Based Lead Generation of 5-Phenyl-1H-pyrazole-3-carboxamide Derivatives
      as Leads for Potent Factor Xia Inhibitors.
AB  - FXIa is suggested as a major target for anticoagulant drug discovery because of
      reduced risk of bleeding. In this paper, we defined 5-phenyl-1H-pyrazole-3
      carboxylic acid derivatives as privileged fragments for FXIa inhibitors' lead
      discovery. After replacing the (E)-3-(5-chloro-2-(1H-tetrazol-1
      yl)phenyl)acrylamide moiety in compound 3 with 5-(3-chlorophenyl)-1H-pyrazole-3
      carboxamide, we traveled from FXIa inhibitor 3 to a scaffold that fused the
      privileged fragments into a pharmacophore for FXIa inhibitors. Subsequently, we
      synthesized and assessed the FXIa inhibitory potency of a series of 5-phenyl-1H
      pyrazole-3-carboxamide derivatives with different P1, P1' and P2'moiety. Finally,
      the SAR of them was systematically investigated to afford the lead compound 7za
      (FXIa Ki = 90.37 nM, 1.5* aPTT in rabbit plasma = 43.33 MUM) which exhibited good
      in vitro inhibitory potency against FXIa and excellent in vitro coagulation
      activities. Furthermore, the binding mode of 7za with FXIa was studied and the
      results suggest that the 2-methylcyclopropanecarboxamide group of 7za makes 2
      direct hydrogen bonds with Tyr58B and Thr35 in the FXIa backbone, making 7za
      binds to FXIa in a highly efficient manner.

PMID- 30103467
TI  - Advances in Micro-Bioreactor Design for Organ Cell Studies.

PMID- 30103468
TI  - Kinetic Resolution of Racemic 2-Hydroxyamides Using a Diphenylacetyl Component as
      an Acyl Source and a Chiral Acyl-Transfer Catalyst.
AB  - Various optically active 2-hydroxyamide derivatives are produced based on the
      kinetic resolution of racemic 2-hydroxyamides with a diphenylacetyl component and
      (R)-benzotetramisole ((R)-BTM), a chiral acyl-transfer catalyst, via asymmetric
      esterification and acylation. It was revealed that a tertiary amide can be used
      with this novel protocol to achieve high selectivity (22 examples; s-value
      reaching over 250). The resulting chiral compounds could be transformed into
      other useful structures while maintaining their chirality.

PMID- 30103466
TI  - Anticancer Effects of Green Tea and the Underlying Molecular Mechanisms in
      Bladder Cancer.
AB  - Green tea and green tea polyphenols (GTPs) are reported to inhibit carcinogenesis
      and malignant behavior in several diseases. Various in vivo and in vitro studies
      have shown that GTPs suppress the incidence and development of bladder cancer.
      However, at present, opinions concerning the anticancer effects and preventive
      role of green tea are conflicting. In addition, the detailed molecular mechanisms
      underlying the anticancer effects of green tea in bladder cancer remain unclear,
      as these effects are regulated by several cancer-related factors. A detailed
      understanding of the pathological roles and regulatory mechanisms at the
      molecular level is necessary for advancing treatment strategies based on green
      tea consumption for patients with bladder cancer. In this review, we discuss the
      anticancer effects of GTPs on the basis of data presented in in vitro studies in
      bladder cancer cell lines and in vivo studies using animal models, as well as new
      treatment strategies for patients with bladder cancer, based on green tea
      consumption. Finally, on the basis of the accumulated data and the main findings,
      we discuss the potential usefulness of green tea as an antibladder cancer agent
      and the future direction of green tea-based treatment strategies for these
      patients.

PMID- 30103469
TI  - Morusin Functions as a Lipogenesis Inhibitor as Well as a Lipolysis Stimulator in
      Differentiated 3T3-L1 and Primary Adipocytes.
AB  - Conflicting results for morusin activity during adipogenic differentiation are
      reported in 3T3-L1 adipocytes and cancer cells. To elucidate the influence of
      morusin on fat metabolism, their anti-obesity effects and molecular mechanism
      were investigated in 3T3-L1 cells and primary adipocytes. Morusin at a dose of
      less than 20 uM does not induce any significant change in the viability of 3T3-L1
      adipocytes. The accumulation of intracellular lipid droplets in 3T3-L1 adipocytes
      stimulated with 0.5 mM 3-isobutyl-1-methylxanthine, 1 uM dexamethasone, 10 ug/mL
      insulin in DMEM containing 10% FBS (MDI)-significantly reduces in a dose
      dependent manner after morusin treatment. The phosphorylation level of members in
      the MAP kinase signaling pathway under the insulin receptor downstream also
      decrease significantly in the MDI + morusin-treated group compared to MDI +
      vehicle-treated group. Also, the expression of adipogenic transcription factors
      (PPARgamma and C/EBPalpha) and lipogenic proteins (aP2 and FAS) are significantly
      attenuated by exposure to the compound in MDI-stimulated 3T3-L1 adipocytes.
      Furthermore, the decrease in the G0/G1 arrest of cell cycle after culturing in
      MDI medium was dramatically recovered after co-culturing in MDI + 20 uM morusin.
      Moreover, morusin treatment induces glycerol release in the primary adipocytes of
      SD rats and enhances lipolytic protein expression (HSL, ATGL, and perilipin) in
      differentiated 3T3-L1 adipocytes. Overall, the results of the present study
      provide strong evidence that morusin inhibits adipogenesis by regulating the
      insulin receptor signaling, cell cycle and adipogenic protein expression as well
      as stimulating lipolysis by enhancing glycerol release and lipolytic proteins
      expression.

PMID- 30103470
TI  - Modulation of Gene Expression in Liver of Hibernating Asiatic Toads (Bufo
      gargarizans).
AB  - Hibernation is an effective energy conservation strategy that has been widely
      adopted by animals to cope with unpredictable environmental conditions. The
      liver, in particular, plays an important role in adaptive metabolic adjustment
      during hibernation. Mammalian studies have revealed that many genes involved in
      metabolism are differentially expressed during the hibernation period. However,
      the differentiation in global gene expression between active and torpid states in
      amphibians remains largely unknown. We analyzed gene expression in the liver of
      active and torpid Asiatic toads (Bufo gargarizans) using RNA-sequencing. In
      addition, we evaluated the differential expression of genes between females and
      males. A total of 1399 genes were identified as differentially expressed between
      active and torpid females. Of these, the expressions of 395 genes were
      significantly elevated in torpid females and involved genes responding to
      stresses, as well as contractile proteins. The expression of 1004 genes were
      significantly down-regulated in torpid females, most which were involved in
      metabolic depression and shifts in the energy utilization. Of the 715
      differentially expressed genes between active and torpid males, 337 were up
      regulated and 378 down-regulated. A total of 695 genes were differentially
      expressed between active females and males, of which 655 genes were significantly
      down-regulated in males. Similarly, 374 differentially expressed genes were
      identified between torpid females and males, with the expression of 252 genes
      (mostly contractile proteins) being significantly down-regulated in males. Our
      findings suggest that expression of many genes in the liver of B. gargarizans are
      down-regulated during hibernation. Furthermore, there are marked sex differences
      in the levels of gene expression, with females showing elevated levels of gene
      expression as compared to males, as well as more marked down-regulation of gene
      expression in torpid males than females.

PMID- 30103471
TI  - Preliminary Efficacy and Feasibility of the "Thinking While Moving in English": A
      Program with Integrated Physical Activity into the Primary School English
      Lessons.
AB  - Background: The physical, cognitive, and learning benefits of physical activity
      for children have already been established. However, many schools are failing to
      provide children with sufficient activity at school due to a crowded school
      curriculum. Physical activity interventions that integrate physical activity with
      learning is a way to enhance physical and cognitive benefits without loss of
      academic time. This study evaluated the preliminary efficacy and feasibility of
      "Thinking While Moving in English", a primary school program that integrates
      physical activity into English lessons. Method: Two classes of Grade 4 students
      (n = 55, 10-11 years old) were randomly assigned to the intervention (n = 29) or
      control (n = 26) conditions. The program components consisted of 3 * 40 min
      physically active academic lessons per week, delivered over a 4-week period. The
      following measures were taken at baseline and immediate post-intervention: on
      task behavior, cognition (inhibition and working memory), and learning outcomes
      (spelling and grammar). Results: Results revealed significant improvements in on
      task behavior and spelling in the intervention group, compared to the control
      group. There were no observed improvements in cognitive outcomes or grammar.
      Conclusions: This study provides preliminary evidence for the efficacy of
      physically active English lessons to enhance children's educational outcomes.

PMID- 30103473
TI  - Species Composition and Trichothecene Genotype Profiling of Fusarium Field
      Isolates Recovered from Wheat in Poland.
AB  - Fusarium head blight (FHB) of cereals is the major head disease negatively
      affecting grain production worldwide. In 2016 and 2017, serious outbreaks of FHB
      occurred in wheat crops in Poland. In this study, we characterized the diversity
      of Fusaria responsible for these epidemics using TaqMan assays. From a panel of
      463 field isolates collected from wheat, four Fusarium species were identified.
      The predominant species were F. graminearum s.s. (81%) and, to a lesser extent,
      F. avenaceum (15%). The emergence of the 15ADON genotype was found ranging from
      83% to 87% of the total trichothecene genotypes isolated in 2016 and 2017,
      respectively. Our results indicate two dramatic shifts within fungal field
      populations in Poland. The first shift is associated with the displacement of F.
      culmorum by F. graminearum s.s. The second shift resulted from a loss of
      nivalenol genotypes. We suggest that an emerging prevalence of F. graminearum
      s.s. may be linked to boosted maize production, which has increased substantially
      over the last decade in Poland. To detect variation within Tri core clusters, we
      compared sequence data from randomly selected field isolates with a panel of
      strains from geographically diverse origins. We found that the newly emerged
      15ADON genotypes do not exhibit a specific pattern of polymorphism enabling their
      clear differentiation from the other European strains.

PMID- 30103475
TI  - 4-Acetyl-Antroquinonol B Suppresses SOD2-Enhanced Cancer Stem Cell-Like
      Phenotypes and Chemoresistance of Colorectal Cancer Cells by Inducing hsa-miR-324
      re-Expression.
AB  - BACKGROUND: Colorectal cancer (CRC) remains a leading cause of cancer-related
      morbidity and mortality in both sexes globally. This is not unconnected with the
      heterogeneity and plasticity of CRC stem cells (CRC-SCs) which stealthily exploit
      the niche-related and (epi)genetic factors to facilitate metastasis,
      chemoresistance, tumor recurrence, and disease progression. Despite the
      accumulating evidence of the role of dysregulated microRNAs in malignancies, the
      therapeutic efficacy of pharmacological-targeting of CRC-SC-associated microRNAs
      is relatively under-explored. EXPERIMENTAL APPROACH: In this present study, we
      employed relatively new bioinformatics approaches, analyses of microarray data,
      Western blot, real-time polymerase chain reaction (RT-PCR), and functional assays
      to show that hsa-miR-324-5p expression is significantly suppressed in CRC cells,
      and inversely correlates with the aberrant expression of SOD2. RESULTS: This
      converse hsa-miR-324-5p/SOD2 relationship is associated with enhanced
      oncogenicity, which is effectively inhibited by 4-acetylantroquinonol B (4-AAQB),
      as evidenced by inhibited cell viability and proliferation, as well as attenuated
      migration, invasion, and clonogenicity in 4-AAQB-treated DLD1 and HCT116 cells.
      Interestingly, 4-AAQB did not affect the viability and proliferation of normal
      colon cells. We also showed that 4-AAQB-induced re-expression of hsa-miR-324-5p,
      akin to short-interfering RNA, reduced SOD2 expression, correlates with the
      concurrent down-regulation of SOD2, N-cadherin, vimentin, c-Myc, and BcL-xL2,
      with concomitant up-regulation of E-cadherin and BAX2 proteins. Enhanced
      expression of hsa-miR-324-5p in the CRC cells suppressed their tumorigenicity in
      vitro and in vivo. Additionally, 4-AAQB synergistically potentiates the FOLFOX
      (folinate (leucovorin), fluorouracil (5FU), and oxaliplatin) anticancer effect by
      eliciting the re-expression of SOD2-suppressed hsa-miR-324, and inhibiting SOD2
      mediated tumorigenicity. CONCLUSION: Our findings highlight the pre-clinical anti
      CSC efficacy of 4-AAQB, with or without FOLFOX in CRC, and suggest a potential
      novel therapeutic strategy for CRC patients.

PMID- 30103472
TI  - Magnolol: A Neolignan from the Magnolia Family for the Prevention and Treatment
      of Cancer.
AB  - The past few decades have witnessed widespread research to challenge
      carcinogenesis; however, it remains one of the most important health concerns
      with the worst prognosis and diagnosis. Increasing lines of evidence clearly show
      that the rate of cancer incidence will increase in future and will create global
      havoc, designating it as an epidemic. Conventional chemotherapeutics and
      treatment with synthetic disciplines are often associated with adverse side
      effects and development of chemoresistance. Thus, discovering novel economic and
      patient friendly drugs that are safe and efficacious is warranted. Several
      natural compounds have proved their potential against this dreadful disease so
      far. Magnolol is a hydroxylated biphenyl isolated from the root and stem bark of
      Magnolia tree. Magnolol can efficiently prevent or inhibit the growth of various
      cancers originating from different organs such as brain, breast, cervical, colon,
      liver, lung, prostate, skin, etc. Considering these perspectives, the current
      review primarily focuses on the fascinating role of magnolol against various
      types of cancers, and the source and chemistry of magnolol and the molecular
      mechanism underlying the targets of magnolol are discussed. This review proposes
      magnolol as a suitable candidate that can be appropriately designed and
      established into a potent anti-cancer drug.

PMID- 30103477
TI  - Advanced Dynamic Cell and Tissue Culture.

PMID- 30103474
TI  - The State of Long Non-Coding RNA Biology.
AB  - Transcriptomic studies have demonstrated that the vast majority of the genomes of
      mammals and other complex organisms is expressed in highly dynamic and cell
      specific patterns to produce large numbers of intergenic, antisense and intronic
      long non-protein-coding RNAs (lncRNAs). Despite well characterized examples,
      their scaling with developmental complexity, and many demonstrations of their
      association with cellular processes, development and diseases, lncRNAs are still
      to be widely accepted as major players in gene regulation. This may reflect an
      underappreciation of the extent and precision of the epigenetic control of
      differentiation and development, where lncRNAs appear to have a central role,
      likely as organizational and guide molecules: most lncRNAs are nuclear-localized
      and chromatin-associated, with some involved in the formation of specialized
      subcellular domains. I suggest that a reassessment of the conceptual framework of
      genetic information and gene expression in the 4-dimensional ontogeny of
      spatially organized multicellular organisms is required. Together with this and
      further studies on their biology, the key challenges now are to determine the
      structure-function relationships of lncRNAs, which may be aided by emerging
      evidence of their modular structure, the role of RNA editing and modification in
      enabling epigenetic plasticity, and the role of RNA signaling in
      transgenerational inheritance of experience.

PMID- 30103478
TI  - Wave Electromechanical Coupling Factor for the Guided Waves in Piezoelectric
      Composites.
AB  - A novel metrics termed the 'wave electromechanical coupling factor' (WEMCF) is
      proposed in this paper, to quantify the coupling strength between the mechanical
      and electric fields during the passage of a wave in piezoelectric composites. Two
      definitions of WEMCF are proposed, leading to a frequency formula and two energy
      formulas for the calculation of such a factor. The frequency formula is naturally
      consistent with the conventional modal electromechanical coupling factor (MEMCF)
      but the implementation is difficult. The energy formulas do not need the
      complicated wave matching required in the frequency formula, therefore are
      suitable for computing. We demonstrated that the WEMCF based on the energy
      formula is consistent with the MEMCF, provided that an appropriate indicator is
      chosen for the electric energy. In this way, both the theoretical closure and the
      computational feasibility are achieved. A numerical tool based on the wave and
      finite element method (WFEM) is developed to implement the energy formulas, and
      it allows the calculation of WEMCF for complex one-dimensional piezoelectric
      composites. A reduced model is proposed to accelerate the computing of the wave
      modes and the energies. The analytical findings and the reduced model are
      numerically validated against two piezoelectric composites with different
      complexity. Eventually an application is given, concerning the use of the shunted
      piezoelectric composite for vibration isolation. A strong correlation among the
      WEMCF, the geometric parameters and the energy transmission loss are observed.
      These results confirm that the proposed WEMCF captures the physics of the
      electromechanical coupling phenomenon associated with the guided waves, and can
      be used to understand, evaluate and design the piezoelectric composites for a
      variety of applications.

PMID- 30103476
TI  - Transcriptome Analysis of JA Signal Transduction, Transcription Factors, and
      Monoterpene Biosynthesis Pathway in Response to Methyl Jasmonate Elicitation in
      Mentha canadensis L.
AB  - Mentha canadensis L. has important economic value for its abundance in essential
      oils. Menthol is the main component of M. canadensis essential oils, which is
      certainly the best-known monoterpene for its simple structure and wide
      applications. However, the regulation of menthol biosynthesis remains elusive in
      M. canadensis. In this study, transcriptome sequencing of M. canadensis with MeJA
      treatment was applied to illustrate the transcriptional regulation of plant
      secondary metabolites, especially menthol biosynthesis. Six sequencing libraries
      were constructed including three replicates for both control check (CK) and
      methyl jasmonate (MeJA) treatment and at least 8 Gb clean bases was produced for
      each library. After assembly, a total of 81,843 unigenes were obtained with an
      average length of 724 bp. Functional annotation indicated that 64.55% of unigenes
      could be annotated in at least one database. Additionally, 4430 differentially
      expressed genes (DEGs) with 2383 up-regulated and 2047 down-regulated transcripts
      were identified under MeJA treatment. Kyoto Encyclopedia of Genes and Genomes
      (KEGG) enrichment indicated that "Monoterpenoid biosynthesis" was one of the most
      significantly enriched pathways in metabolism. Subsequently, DEGs involved in JA
      signal transduction, transcription factors, and monoterpene biosynthesis were
      analyzed. 9 orthologous genes involved in menthol biosynthesis were also
      identified. This is the first report of a transcriptome study of M. canadensis
      and will facilitate the studies of monoterpene biosynthesis in the genus Mentha.

PMID- 30103479
TI  - UV Monitoring for Public Health.
AB  - Overexposure to solar ultraviolet (UV) radiation is a risk for public health.
      Therefore, it is important to provide information to the public about the level
      of solar UV. The UV-Index (UVI) is the relevant quantity, expressing the
      erythemally weighted irradiance to a horizontal plane on a simple scale. As solar
      UV irradiance is strongly variable in time and space, measurements within a
      network provide the best source of information, provided they can be made
      available rapidly. However, to ensure the information is reliable, strict quality
      assurance/quality control (QA/QC) procedures for the monitoring networks are
      necessary. Near real time presentation of the measured UVI on web-pages is the
      best way to inform the public. The interpretation of the data in terms of the
      individual 'allowable' exposure time is heavily impacted by skin type, behavior,
      and clothing, and must be learned for each person through experience and
      guidance. Nonetheless, reliable knowledge of the actual level of the intensity of
      erythemally weighted irradiance and its variability forms the basis of education
      and public awareness. The challenges and requirements in providing comprehensive
      UVI data for public health guidance are here considered.

PMID- 30103480
TI  - Validation and Feasibility of the Medication Acceptability Questionnaire to
      Investigate Tablet and Liquid Alendronic Acid with Older Hospital Patients.
AB  - The effects of formulation characteristics on acceptability are poorly
      understood. This study evaluated the validity and feasibility of using the
      Medication Acceptability Questionnaire (MAQ) to investigate factors influencing
      acceptability of tablet compared with liquid alendronic acid. Written consent was
      obtained from eligible patients on Older People's Medicine wards. MAQ face and
      content validity were evaluated through cognitive interviews while internal
      consistency and criterion validity were investigated by calculating Cronbach's
      alpha and correlation of MAQ items with visual analogue scale (VAS) responses.
      MAQ data were obtained from 33 and 25 participants for tablet and liquid
      formulations respectively. Cognitive interviews indicated MAQ face and content
      validity. The domains of appearance, efficacy, and tolerability demonstrated
      adequate internal consistency and suitable refinements were identified for the
      domains of convenience and taste with Cronbach's alpha <0.7. Significant positive
      correlations were identified between all MAQ domains and VAS. The liquid trended
      towards performing better for taste, appearance and tolerability and the tablet
      for convenience and efficacy. It is feasible to capture patient acceptability of
      a medication by questionnaire. Interpatient variation in acceptability for two
      formulations indicates that medication characteristics should be considered
      during prescribing and medication reviews to match patient preference with the
      appropriate formulation.

PMID- 30103482
TI  - Evolution Characteristics of Surface Water Quality Due to Climate Change and LUCC
      under Scenario Simulations: A Case Study in the Luanhe River Basin.
AB  - It is of great significance to study the effects and mechanisms of the key
      driving forces of surface water quality deterioration-climate change and LUCC
      (land use and land cover change). The Luanhe River Basin (LRB) in north-eastern
      China was examined for qualitatively and quantitatively assessing the responses
      of total nitrogen (TN) and total phosphorus (TP) loads on different climate
      scenarios and LUCC scenarios. The results show that from 1963 to 2017, the TN and
      TP loads basically presented a negative correlation with the temperature change
      (except for winter), while showing a significant positive correlation with the
      precipitation change. The incidence of TN pollution is sensitive to temperature
      increase. From 2020 to 2050, the annual average loads of TN and TP were slightly
      lower than from 1963 to 2017. The contribution of rising temperature was more
      significant on nutrient loads. Also, the incidence of TN pollution is sensitive
      to the future climate change. Under LUCC scenarios, the TN and TP loads and
      pollution incidence increased correspondingly with the decrease of natural land.
      The evolution characteristics analysis can provide support for the effect and
      adaptation-strategies study of climate change and LUCC on surface water quality.

PMID- 30103481
TI  - Diversity of Myxobacteria-We Only See the Tip of the Iceberg.
AB  - The discovery of new antibiotics is mandatory with regard to the increasing
      number of resistant pathogens. One approach is the search for new antibiotic
      producers in nature. Among actinomycetes, Bacillus species, and fungi,
      myxobacteria have been a rich source for bioactive secondary metabolites for
      decades. To date, about 600 substances could be described, many of them with
      antibacterial, antifungal, or cytostatic activity. But, recent cultivation
      independent studies on marine, terrestrial, or uncommon habitats unequivocally
      demonstrate that the number of uncultured myxobacteria is much higher than would
      be expected from the number of cultivated strains. Although several highly
      promising myxobacterial taxa have been identified recently, this so-called Great
      Plate Count Anomaly must be overcome to get broader access to new secondary
      metabolite producers. In the last years it turned out that especially new
      species, genera, and families of myxobacteria are promising sources for new
      bioactive metabolites. Therefore, the cultivation of the hitherto uncultivable
      ones is our biggest challenge.

PMID- 30103483
TI  - Pharmacologic Treatment Options for Insomnia in Patients with Schizophrenia.
AB  - Background: Symptoms of sleep disorders, such as disturbances in sleep initiation
      and continuity, are commonly reported in patients with schizophrenia, especially
      in the acute phase of illness. Studies have shown that up to 80% of patients
      diagnosed with schizophrenia report symptoms of insomnia. Sleep disturbances have
      been shown to increase the risk of cognitive dysfunction and relapse in patients
      with schizophrenia. Currently, there are no medications approved specifically for
      the treatment of insomnia in patients with schizophrenia. Methods: A literature
      search was performed through OVID and PubMed to compile publications of
      pharmacotherapy options studied to treat insomnia in patients with schizophrenia.
      Articles were reviewed from 1 January 2000 through 1 March 2018 with some
      additional earlier articles selected if deemed by the authors to be particularly
      relevant. Results: Pharmacotherapies collected from the search results that were
      reviewed and evaluated included melatonin, eszopiclone, sodium oxybate, and
      antipsychotics. Conclusions: Overall, this review confirmed that there are a few
      evidence-based options to treat insomnia in patients with schizophrenia,
      including selecting a more sedating second-generation antipsychotic such as
      paliperidone, or adding melatonin or eszopiclone. Further randomized controlled
      trials are needed.

PMID- 30103484
TI  - A Novel and Safe Approach to Simulate Cutting Movements Using Ground Reaction
      Forces.
AB  - Control of shear ground reaction forces (sGRF) is important in performing running
      and cutting tasks as poor sGRF control has implications for those with knee
      injuries, such as anterior cruciate ligament (ACL) ruptures. The goal of this
      study was to develop a novel and safe task to evaluate control or accurate
      modulation of shear ground reaction forces related to those generated during
      cutting. Our approach utilized a force control task using real-time visual
      feedback of a subject's force production and evaluated control capabilities
      through accuracy and divergence measurements. Ten healthy recreational athletes
      completed the force control task while force control via accuracy measures and
      divergence calculations was investigated. Participants were able to accurately
      control sGRF in multiple directions based on error measurements. Forces generated
      during the task were equal to or greater than those measured during a number of
      functional activities. We found no significant difference in the divergence of
      the force profiles using the Lyapunov Exponent of the sGRF trajectories.
      Participants using our approach produced high accuracy and low divergence force
      profiles and functional force magnitudes. Moving forward, we will utilize this
      task in at-risk populations who are unable to complete a cutting maneuver in
      early stages of rehabilitation, such as ACL deficient and newly reconstructed
      individuals, allowing insight into force control not obtainable otherwise.

PMID- 30103485
TI  - Cationic High Molecular Weight Lignin Polymer: A Flocculant for the Removal of
      Anionic Azo-Dyes from Simulated Wastewater.
AB  - The presence of dyes in wastewater effluents made from the textile industry is a
      major environmental problem due to their complex structure and poor
      biodegradability. In this study, a cationic lignin polymer was synthesized via
      the free radical polymerization of lignin with [2-(methacryloyloxy) ethyl]
      trimethyl ammonium chloride (METAC) and used to remove anionic azo-dyes (reactive
      black 5, RB5, and reactive orange 16, RO16) from simulated wastewater. The
      effects of pH, salt, and concentration of dyes, as well as the charge density and
      molecular weight of lignin-METAC polymer on dye removal were examined. Results
      demonstrated that lignin-METAC was an effective flocculant for the removal of dye
      via charge neutralization and bridging mechanisms. The dye removal efficiency of
      lignin-METAC polymer was independent of pH. The dosage of the lignin polymer
      required for reaching the maximum removal had a linear relationship with the dye
      concentration. The presence of inorganic salts including NaCl, NaNO3, and Na2SO4
      had a marginal effect on the dye removal. Under the optimized conditions, greater
      than 98% of RB5 and 94% of RO16 were removed at lignin-METAC concentrations of
      120 mg/L and 105 mg/L in the dye solutions, respectively.

PMID- 30103487
TI  - Folate, Vitamin B6 and Vitamin B12 Intake in Relation to Hyperuricemia.
AB  - To assess the association between intake of folate, vitamin B6, and vitamin B12
      with hyperuricemia (HU) among adults from the United States (US), we extracted
      relevant data from 24,975 US adults aged 20-85 years from the National Health and
      Nutrition Examination Survey (NHANES) in 2001-2014. All dietary intake was
      evaluated by 24-h dietary recalls. Multivariable logistic regression analysis was
      performed to explore the associations after adjustment for confounders. Compared
      to the lowest quintile (Q1), for males, adjusted odds ratios (ORs) of HU in Q2 to
      Q5 of folate (dietary folate equivalent, DFE) intake were 0.84 (95% CI, 0.73
      0.96), 0.84 (0.73-0.97), 0.72 (0.62-0.84), and 0.64 (0.53-0.77), respectively (p
      for trend <0.0001). In females, adjusted ORs in Q2 to Q4 of folate (DFE) intake
      were 0.84 (95% CI, 0.71-0.99), 0.81 (0.68-0.96), and 0.82 (0.68-0.99), with a p
      for trend of 0.1475. Our findings indicated the intakes of total folate, folic
      acid, food folate, folate (DFE), vitamin B12, but not vitamin B6, were inversely
      related to the risk of HU in males. A lower risk of HU with higher intakes of
      total folate, food folate, and folate (DFE) was found in females, but with no
      association between intakes of folic acid, vitamin B6, B12, and the risk of HU
      for females.

PMID- 30103486
TI  - Ultraviolet Irradiation of Skin Alters the Faecal Microbiome Independently of
      Vitamin D in Mice.
AB  - Reduced sunlight exposure has been associated with an increased incidence of
      Crohn's disease and ulcerative colitis. The effect of ultraviolet radiation (UVR)
      on the faecal microbiome and susceptibility to colitis has not been explored.
      C57Bl/6 female mice were fed three different vitamin D-containing diets for 24
      days before half of the mice in each group were UV-irradiated (1 kJ/m2) for each
      of four days, followed by twice-weekly irradiation of shaved dorsal skin for 35
      days. Faecal DNA was extracted and high-throughput sequencing of the 16S RNA gene
      performed. UV irradiation of skin was associated with a significant change in the
      beta-diversity of faeces compared to nonirradiated mice, independently of vitamin
      D. Specifically, members of phylum Firmicutes, including Coprococcus, were
      enriched, whereas members of phylum Bacteroidetes, such as Bacteroidales, were
      depleted. Expression of colonic CYP27B1 increased by four-fold and IL1beta
      decreased by five-fold, suggesting a UVR-induced anti-inflammatory effect. UV
      irradiated mice, however, were not protected against colitis induced by dextran
      sodium sulfate (DSS), although distinct faecal microbiome differences were
      documented post-DSS between UV-irradiated and nonirradiated mice. Thus, skin
      exposure to UVR alters the faecal microbiome, and further investigations to
      explore the implications of this in health and disease are warranted.

PMID- 30103488
TI  - The Generation of CAR-Transfected Natural Killer T Cells for the Immunotherapy of
      Melanoma.
AB  - Natural killer T (NKT) cells represent a cell subpopulation that combines
      characteristics of natural killer (NK) cells and T cells. Through their
      endogenous T-cell receptors (TCRs), they reveal a pronounced intrinsic anti-tumor
      activity. Thus, a NKT cell transfected with a chimeric antigen receptor (CAR),
      which recognizes a tumor-specific surface antigen, could attack tumor cells
      antigen-specifically via the CAR and additionally through its endogenous TCR. NKT
      cells were isolated from peripheral blood mononuclear cells (PBMCs), expanded,
      and electroporated with mRNA encoding a chondroitin sulfate proteoglycan 4
      (CSPG4)-specific CAR. The CAR expression on NKT cells and their in vitro
      functionality were analyzed. A transfection efficiency of more than 80% was
      achieved. Upon stimulation with melanoma cells, CAR-NKT cells produced cytokines
      antigen-specifically. Compared with conventional CAR-T cells, cytokine secretion
      of CAR-NKT cells was generally lower. Specific cytotoxicity, however, was similar
      with CAR-NKT cells showing a trend towards improved cytotoxicity. Additionally,
      CAR-NKT cells could kill target cells through their endogenous TCRs. In summary,
      it is feasible to generate CAR-NKT cells by using mRNA electroporation. Their CAR
      mediated cytotoxicity is at least equal to that of conventional CAR-T cells,
      while their intrinsic cytotoxic activity is maintained. Thus, CAR-NKT cells may
      represent a valuable alternative to conventional CAR-T cells for cancer
      immunotherapy.

PMID- 30103490
TI  - An Improved Electronic Image Motion Compensation (IMC) Method of Aerial Full
      Frame-Type Area Array CCD Camera Based on the CCD Multiphase Structure and
      Hardware Implementation.
AB  - In this paper, the performance of the electronic conventional image motion
      compensation (IMC) method based on the time delay integration (TDI) mode was
      analyzed using the optical injection formula of charge coupled devices (CCDs).
      The result shows that the non-synchronous effect of charge packet transfer caused
      by line-by-line transfer during exposure makes the compensated image
      dissatisfying. Then an improved electronic IMC method based on the CCD multiphase
      structure was proposed. In this method, a series of proper driving clocks were
      applied to drive the charge packet to move electrode-by-electrode during the
      exposure time, which results in a minimum non-synchronous effect of charge packet
      transfer. The mismatch of velocity between charge packet transfer and image
      motion was decreased. The performance of the improved electronic IMC method was
      also analyzed using the optical injection formula. The modulation degrees of the
      two methods were compared. The average value of the modulation degree of the
      improved electronic IMC method was 47/96, greater than the conventional
      electronic IMC method, which was 1/3. To achieve the improved electronic IMC, the
      driver timing diagram of the improved electronic IMC method was proposed. This
      paper presented an improved hardware implementation method for the improved
      electronic IMC method. Based on the basic FTF4052M drive circuit system, an IMC
      pulse pattern generator that worked together with the main pulse pattern
      generator (SAA8103) was added to achieve the improved electronic IMC. Then, the
      internal structure of the IMC pulse pattern generator was given. A dual pulse
      pattern generator drive circuit system was proposed. After computer simulation
      and indoor real shot verification, the compensation effect of the improved
      electronic IMC method was better than the compensation effect of the conventional
      electronic IMC method.

PMID- 30103491
TI  - Comparison of Different Electricity-Based Thermal Pretreatment Methods for
      Enhanced Bioenergy Production from Municipal Sludge.
AB  - This paper presents results for a comprehensive study that compares the
      performance of three electricity-based thermal pretreatment methods for improving
      the effectiveness of anaerobic digestion (AD) to process municipal wastewater
      sludge. The study compares thermal pretreatment using conventional heating (CH),
      microwave (MW), and radio frequency (RF) heating techniques. The effectiveness of
      the pretreatment methods was assessed in terms of chemical oxygen demand (COD)
      and biopolymers solubilization, AD bioenergy production, input electrical energy,
      and overall net energy production of the sequential pretreatment/AD process. The
      heating applicators for the bench-scale testing consisted of a custom-built
      pressure-sealed heating vessel for CH experiments, an off-the-shelf programmable
      MW oven operating at a frequency of 2.45 GHz for MW heating experiments, and a
      newly developed 1 kW RF heating system operating at a frequency of 13.56 MHz for
      RF heating experiments. Under identical thermal profiles, all three thermal
      pretreatment methods achieved similar sludge disintegration in terms of COD and
      biopolymer solubilization as well as AD bioenergy production (p-value > 0.05).
      According to the energy assessment results, the application of CH and MW
      pretreatments resulted in overall negative energy production, while positive net
      energy production was obtained through the sequential pretreatment/AD process
      utilizing RF pretreatment.

PMID- 30103492
TI  - PHAROS-PHysical Assistant RObot System.
AB  - The great demographic change leading to an ageing society demands technological
      solutions to satisfy the increasing varied elderly needs. This paper presents
      PHAROS, an interactive robot system that recommends and monitors physical
      exercises designed for the elderly. The aim of PHAROS is to be a friendly elderly
      companion that periodically suggests personalised physical activities, promoting
      healthy living and active ageing. Here, it is presented the PHAROS architecture,
      components and experimental results. The architecture has three main strands: a
      Pepper robot, that interacts with the users and records their exercises
      performance; the Human Exercise Recognition, that uses the Pepper recorded
      information to classify the exercise performed using Deep Leaning methods; and
      the Recommender, a smart-decision maker that schedules periodically personalised
      physical exercises in the users' agenda. The experimental results show a high
      accuracy in terms of detecting and classifying the physical exercises (97.35%)
      done by 7 persons. Furthermore, we have implemented a novel procedure of rating
      exercises on the recommendation algorithm. It closely follows the users' health
      status (poor performance may reveal health problems) and adapts the suggestions
      to it. The history may be used to access the physical condition of the user,
      revealing underlying problems that may be impossible to see otherwise.

PMID- 30103494
TI  - Effect of Selenium on the Responses Induced by Heat Stress in Plant Cell
      Cultures.
AB  - High temperatures are a significant stress factor for plants. In fact, many
      biochemical reactions involved in growth and development are sensitive to
      temperature. In particular, heat stress (HS) represents a severe issue for plant
      productivity and strategies to obtain high yields under this condition are
      important goals in agriculture. While selenium (Se) is a nutrient for humans and
      animals, its role as a plant micronutrient is still questioned. Se can prevent
      several abiotic stresses (drought, heat, UV, salinity, heavy metals), but the
      action mechanisms are poorly understood. Se seems to regulate reactive oxygen
      species (ROS) and to inhibit heavy metals transport. In addition, it has been
      demonstrated that Se is essential for a correct integrity of cell membranes and
      chloroplasts, especially the photosynthetic apparatus. Previous results showed
      that in tobacco (Nicotiana tabacum cv. Bright-Yellow 2) cultures HS (5 min at 50 
      degrees C) induced cell death with apoptotic features, accompanied by oxidative
      stress and changes in the levels of stress-related proteins. In this work we
      investigated the effect of Se on the responses induced by HS. The obtained
      results show that Se markedly reduces the effects of HS on cell vitality,
      cytoplasmic shrinkage, superoxide anion production, membrane lipids peroxidation,
      activity of caspase-3-like proteases, and the levels of some stress-related
      proteins (Hsp90, BiP, 14-3-3s, cytochrome c).

PMID- 30103489
TI  - TRP Channels as Sensors of Bacterial Endotoxins.
AB  - The cellular and systemic effects induced by bacterial lipopolysaccharides (LPS)
      have been solely attributed to the activation of the Toll-like receptor 4 (TLR4)
      signalling cascade. However, recent studies have shown that LPS activates several
      members of the Transient Receptor Potential (TRP) family of cation channels.
      Indeed, LPS induces activation of the broadly-tuned chemosensor TRPA1 in sensory
      neurons in a TLR4-independent manner, and genetic ablation of this channel
      reduced mouse pain and inflammatory responses triggered by LPS and the gustatory
      mediated avoidance to LPS in fruit flies. LPS was also shown to activate TRPV4
      channels in airway epithelial cells, an effect leading to an immediate production
      of bactericidal nitric oxide and to an increase in ciliary beat frequency. In
      this review, we discuss the role of TRP channels as sensors of bacterial
      endotoxins, and therefore, as crucial players in the timely detection of invading
      gram-negative bacteria.

PMID- 30103496
TI  - Sequential Production of Levulinic Acid and Porous Carbon Material from
      Cellulose.
AB  - A sequential production of levulinic acid (LA) and porous carbon material (CM)
      from cellulose was conducted by a two-step process. The cellulose was first acid
      hydrolyzed, and the preferred reaction conditions required a severity factor of
      4.0-4.5, in which the yields of LA, formic acid, and solid residue were 38 +/- 3
      wt%, 17 +/- 3 wt%, and 15 +/- 3 wt%, respectively. The solid residue was further
      used for CM preparation through pyrolysis, with or without ZnCl2 activation. The
      ZnCl2 activation promoted the formation of CMs with improved thermal stability,
      high surface area (1184-2510 m2/g), and excellent phenol adsorption capacity (136
      172 mg/g). The used CM can be easily regenerated by a simple methanol Soxhlet
      extraction process, and a comparable phenol adsorption capacity of 97 mg/g was
      maintained for the 5th reusing. Finally, 100 g cellulose produced 40.5 g LA, 18.9
      g formic acid and 8.5 g porous CM, with a total carbon utilization ratio reaching
      74.4%.

PMID- 30103497
TI  - Preparation of a Highly Porous Carbon Material Based on Quinoa Husk and Its
      Application for Removal of Dyes by Adsorption.
AB  - A porous carbon material was prepared from quinoa husk (QH) by carbonization and
      chemical activation with KOH. A series of experiments, including SEM (Scanning
      electron microscopy), FT-IR (Fourier transform infrared), XRD (X-ray
      diffraction), Raman, X-ray photoelectron spectroscopy (XPS), and N2
      adsorption/desorption, were carried out on the porous carbon produced from quinoa
      husk (PC-QH). The results showed that PC-QH was mainly composed of activated
      carbon and graphite. Moreover, PC-QH exhibited a high level of porosity with a
      BET (the Brunauer-Emmett-Teller theory) surface area of 1713 m2 g-1. As a
      representative dye, malachite green (MG) was selected to evaluate the performance
      of PC-QH to absorb the contaminants in dyeing wastewater. In batch adsorption
      experiments, PC-QH exhibited a high adsorption rate toward malachite green (MG).
      An uptake capacity of 599.90 mg g-1 was achieved in the initial 5 min, and the MG
      adsorption capacity of PC-QH reached 1365.10 mg g-1, which was higher than many
      other adsorbents. The adsorption data were well fitted with the Freundlich
      isotherm model and the pseudo-second-order kinetic model. PC-QH also displayed a
      high absorption rate to rhodamine B (RhB), methyl violet (MV), methylene blue
      (MB), and methyl orange (MO). The results in this study suggest that PC-QH can be
      a promising adsorbent for quick treatment of dyeing wastewater.

PMID- 30103495
TI  - MicroRNAs in Cardiac Autophagy: Small Molecules and Big Role.
AB  - Autophagy, which is an evolutionarily conserved process according to the
      lysosomal degradation of cellular components, plays a critical role in
      maintaining cell homeostasis. Autophagy and mitochondria autophagy (mitophagy)
      contribute to the preservation of cardiac homeostasis in physiological settings.
      However, impaired or excessive autophagy is related to a variety of diseases.
      Recently, a close link between autophagy and cardiac disorders, including
      myocardial infarction, cardiac hypertrophy, cardiomyopathy, cardiac fibrosis, and
      heart failure, has been demonstrated. MicroRNAs (miRNAs) are a class of small non
      coding RNAs with a length of approximately 21-22 nucleotides (nt), which are
      distributed widely in viruses, plants, protists, and animals. They function in
      mediating the post-transcriptional gene silencing. A growing number of studies
      have demonstrated that miRNAs regulate cardiac autophagy by suppressing the
      expression of autophagy-related genes in a targeted manner, which are involved in
      the pathogenesis of heart diseases. This review summarizes the role of microRNAs
      in cardiac autophagy and related cardiac disorders. Furthermore, we mainly
      focused on the autophagy regulation pathways, which consisted of miRNAs and their
      targeted genes.

PMID- 30103498
TI  - A Deep Feature Learning Method for Drill Bits Monitoring Using the Spectral
      Analysis of the Acoustic Signals.
AB  - Machine fault diagnosis (MFD) has gained an important enthusiasm since the
      unfolding of the pattern recognition techniques in the last three decades. It
      refers to all of the studies that aim to automatically detect the faults on the
      machines using various kinds of signals that they can generate. The present work
      proposes a MFD system for the drilling machines that is based on the sounds they
      produce. The first key contribution of this paper is to present a system
      specifically designed for the drills, by attempting not only to detect the faulty
      drills but also to detect whether the sounds were generated during the active or
      the idling stage of the whole machinery system, in order to provide a complete
      remote control. The second key contribution of the work is to represent the power
      spectrum of the sounds as images and apply some transformations on them in order
      to reveal, expose, and emphasize the health patterns that are hidden inside them.
      The created images, the so-called power spectrum density (PSD)-images, are then
      given to a deep convolutional autoencoder (DCAE) for a high-level feature
      extraction process. The final step of the scheme consists of adopting the
      proposed PSD-images + DCAE features as the final representation of the original
      sounds and utilize them as the inputs of a nonlinear classifier whose outputs
      will represent the final diagnosis decision. The results of the experiments
      demonstrate the high discrimination potential afforded by the proposed PSD-images
      + DCAE features. They were also tested on a noisy dataset and the results show
      their robustness against noises.

PMID- 30103493
TI  - Repair of Damaged Articular Cartilage: Current Approaches and Future Directions.
AB  - Articular hyaline cartilage is extensively hydrated, but it is neither innervated
      nor vascularized, and its low cell density allows only extremely limited self
      renewal. Most clinical and research efforts currently focus on the restoration of
      cartilage damaged in connection with osteoarthritis or trauma. Here, we discuss
      current clinical approaches for repairing cartilage, as well as research
      approaches which are currently developing, and those under translation into
      clinical practice. We also describe potential future directions in this area,
      including tissue engineering based on scaffolding and/or stem cells as well as a
      combination of gene and cell therapy. Particular focus is placed on cell-based
      approaches and the potential of recently characterized chondro-progenitors;
      progress with induced pluripotent stem cells is also discussed. In this context,
      we also consider the ability of different types of stem cell to restore hyaline
      cartilage and the importance of mimicking the environment in vivo during cell
      expansion and differentiation into mature chondrocytes.

PMID- 30103499
TI  - Feasibility of A Novel On-Site Detection Method for Aflatoxin in Maize Flour from
      Markets and Selected Households in Kampala, Uganda.
AB  - In sub-Saharan Africa, there is a high demand for affordable and accessible
      methods for on-site detection of aflatoxins for appropriate food safety
      management. In this study, we validated an electrochemical immunosensor device by
      the on-site detection of 60 maize flour samples from six markets and 72 samples
      from households in Kampala. The immunosensor was successfully validated with a
      linear range from 0.7 +/- 0.1 to 11 +/- 0.3 ug/kg and limit of detection (LOD) of
      0.7 ug/kg. The maize flour samples from the markets had a mean total aflatoxin
      concentration of 7.6 +/- 2.3 ug/kg with approximately 20% of the samples higher
      than 10 ug/kg, which is the maximum acceptable level in East Africa. Further down
      the distribution chain, at the household level, approximately 45% of the total
      number contained total aflatoxin levels higher than the acceptable limit. The on
      site detection method correlated well with the established laboratory-based HPLC
      and ELISA-detection methods for aflatoxin B1 with the correlation coefficients of
      0.94 and 0.98, respectively. This study shows the feasibility of a novel on-site
      detection method and articulates the severity of aflatoxin contamination in
      Uganda.

PMID- 30103500
TI  - Experimental Study on Residual Bending Strength of Corroded Reinforced Concrete
      Beam Based on Micromagnetic Sensor.
AB  - This paper presents a nondestructive test method to evaluate the residual bending
      strength of corroded reinforced concrete beam by analyzing the self-magnetic flux
      leakage (SMFL) signals. The automatic scanning device was equipped with a
      micromagnetic sensor and sensor-based experimental details were introduced. Next,
      the theoretical formula of the normal component HS(z) of the SMFL signal that
      originated from the corroded region was derived based on the magnetic dipole
      model and the experimental results were discussed. The results indicate that the
      experimental data of HS(z) are consistent with the theoretical calculations, both
      location and extent of the steel bars corrosion can be qualitatively determined
      by using HS(z). The gradient K of HS(z) is approximately linearly related to the
      loss rate, S, of the bending strength, which can be used to evaluate the residual
      bending strength of the corroded reinforced concrete beam. This work lays the
      foundation for evaluating the residual bending strength of corroded reinforced
      concrete beams using the SMFL signal; the micromagnetic sensor is further applied
      to the civil engineering.

PMID- 30103503
TI  - Use of Estimating Equations for Dosing Antimicrobials in Patients with Acute
      Kidney Injury Not Receiving Renal Replacement Therapy.
AB  - Acute kidney injury (AKI) can potentially lead to the accumulation of
      antimicrobial drugs with significant renal clearance. Drug dosing adjustments are
      commonly made using the Cockcroft-Gault estimate of creatinine clearance (CLcr).
      The Modified Jelliffe equation is significantly better at estimating kidney
      function than the Cockcroft-Gault equation in the setting of AKI. The objective
      of this study is to assess the degree of antimicrobial dosing discordance using
      different glomerular filtration rate (GFR) estimating equations. This is a
      retrospective evaluation of antimicrobial dosing using different estimating
      equations for kidney function in AKI and comparison to Cockcroft-Gault estimation
      as a reference. Considering the Cockcroft-Gault estimate as the criterion
      standard, antimicrobials were appropriately adjusted at most 80.7% of the time.
      On average, kidney function changed by 30 mL/min over the course of an AKI
      episode. The median clearance at the peak serum creatinine was 27.4 (9.3-66.3)
      mL/min for Cockcroft Gault, 19.8 (9.8-47.0) mL/min/1.73 m2 for MDRD and 20.5 (4.9
      49.6) mL/min for the Modified Jelliffe equations. The discordance rate for
      antimicrobial dosing ranged from a minimum of 8.6% to a maximum of 16.4%. In the
      event of discordance, the dose administered was supra-therapeutic 100% of the
      time using the Modified Jelliffe equation. Use of estimating equations other than
      the Cockcroft Gault equation may significantly alter dosing of antimicrobials in
      AKI.

PMID- 30103504
TI  - Over-Wrapping of the Aortic Wall with an Elastic Extra-Aortic Wrap Results in
      Luminal Creasing.
AB  - Elastic extra-aortic wrapping is a potential non-pharmacological way to improve
      aortic compliance and treat isolated systolic hypertension associated with a
      stiffened aorta. We aimed to use computer simulations to re-evaluate whether
      there is aortic shape distortion in aortic wrapping to achieve greater elasticity
      of the wrapped aortic segment. Non-linear transient numerical analysis based on
      an idealized hyper-elastic single-layered aorta model was performed to simulate
      the force/displacement regimes of external aortic wrapping. Pressure-displacement
      relationships were used to establish model aortic wall distensibilities of 4.3
      and 5.5 (10-3 mmHg-1). A physiological pulsatile lumen pressure was employed to
      estimate the potential improvements in aortic distensibility by compression
      forces representing elastic aortic wrapping. In the less distensible model of the
      aortic wall there was increased systolic expansion in the wrapped segment. We
      found a risk of creasing of the aortic luminal wall with wrapping. Sufficient
      unloading of a thick and elastic aortic wall to induce increased compliance, as
      observed in elastic wrapping, is associated with the potential risk of over
      compression and folding (creasing) inside the lumen.

PMID- 30103501
TI  - Going (Reo)Viral: Factors Promoting Successful Reoviral Oncolytic Infection.
AB  - Oncolytic viruses show intriguing potential as cancer therapeutic agents. These
      viruses are capable of selectively targeting and killing cancerous cells while
      leaving healthy cells largely unaffected. The use of oncolytic viruses for cancer
      treatments in selected circumstances has recently been approved by the Food and
      Drug Administration (FDA) of the US and work is progressing on engineering viral
      vectors for enhanced selectivity, efficacy and safety. However, a better
      fundamental understanding of tumour and viral biology is essential for the
      continued advancement of the oncolytic field. This knowledge will not only help
      to engineer more potent and effective viruses but may also contribute to the
      identification of biomarkers that can determine which patients will benefit most
      from this treatment. A mechanistic understanding of the overlapping activity of
      viral and standard chemotherapeutics will enable the development of better
      combinational approaches to improve patient outcomes. In this review, we will
      examine each of the factors that contribute to productive viral infections in
      cancerous cells versus healthy cells. Special attention will be paid to reovirus
      as it is a well-studied virus and the only wild-type virus to have received
      orphan drug designation by the FDA. Although considerable insight into reoviral
      biology exists, there remain numerous deficiencies in our understanding of the
      factors regulating its successful oncolytic infection. Here we will discuss what
      is known to regulate infection as well as speculate about potential new
      mechanisms that may enhance successful replication. A joint appreciation of both
      tumour and viral biology will drive innovation for the next generation of
      reoviral mediated oncolytic therapy.

PMID- 30103502
TI  - Role of Cytochrome P450 Enzymes in the Metabolic Activation of Tyrosine Kinase
      Inhibitors.
AB  - Tyrosine kinase inhibitors are a rapidly expanding class of molecular targeted
      therapies for the treatment of various types of cancer and other diseases. An
      increasing number of clinically important small molecule tyrosine kinase
      inhibitors have been shown to undergo cytochrome P450-mediated bioactivation to
      form chemically reactive, potentially toxic products. Metabolic activation of
      tyrosine kinase inhibitors is proposed to contribute to the development of
      serious adverse reactions, including idiosyncratic hepatotoxicity. This article
      will review recent findings and ongoing studies to elucidate the link between
      drug metabolism and tyrosine kinase inhibitor-associated hepatotoxicity.

PMID- 30103506
TI  - Buckling-Based Non-Linear Mechanical Sensor.
AB  - Mechanical sensors provide core keys for high-end research in quantitative
      understanding of fundamental phenomena and practical applications such as the
      force or pressure sensor, accelerometer and gyroscope. In particular, in situ
      sensitive and reliable detection is essential for measurements of the mechanical
      vibration and displacement forces in inertial sensors or seismometers. However,
      enhancing sensitivity, reducing response time and equipping sensors with a
      measurement capability of bidirectional mechanical perturbations remains
      challenging. Here, we demonstrate the buckling cantilever-based non-linear
      dynamic mechanical sensor which addresses intrinsic limitations associated with
      high sensitivity, reliability and durability. The cantilever is attached on to a
      high-Q tuning fork and initially buckled by being pressed against a solid surface
      while a flexural stress is applied. Then, buckling instability occurs near the
      bifurcation region due to lateral movement, which allows high-sensitive detection
      of the lateral and perpendicular surface acoustic waves with bandwidth-limited
      temporal response of less than 1 ms.

PMID- 30103505
TI  - Seasonal and Sexual Differences in the Microbiota of the Hoopoe Uropygial
      Secretion.
AB  - The uropygial gland of hoopoe nestlings and nesting females hosts bacterial
      symbionts that cause changes in the characteristics of its secretion, including
      an increase of its antimicrobial activity. These changes occur only in nesting
      individuals during the breeding season, possibly associated with the high
      infection risk experienced during the stay in the hole-nests. However, the
      knowledge on hoopoes uropygial gland microbial community dynamics is quite
      limited and based so far on culture-dependent and molecular fingerprinting
      studies. In this work, we sampled wild and captive hoopoes of different sex, age,
      and reproductive status, and studied their microbiota using quantitative
      polymerase chain reaction (qPCR), fluorescence in situ hybridization (FISH) and
      pyrosequencing. Surprisingly, we found a complex bacterial community in all
      individuals (including non-nesting ones) during the breeding season.
      Nevertheless, dark secretions from nesting hoopoes harbored significantly higher
      bacterial density than white secretions from breeding males and both sexes in
      winter. We hypothesize that bacterial proliferation may be host-regulated in
      phases of high infection risk (i.e., nesting). We also highlight the importance
      of specific antimicrobial-producing bacteria present only in dark secretions that
      may be key in this defensive symbiosis. Finally, we discuss the possible role of
      environmental conditions in shaping the uropygial microbiota, based on
      differences found between wild and captive hoopoes.

PMID- 30103507
TI  - Application of Air-Coupled Ultrasonic Arrays for Excitation of a Slow
      Antisymmetric Lamb Wave.
AB  - Air-coupled excitation and reception of ultrasonic guided waves is already used
      for non-destructive testing and evaluation (NDT & E). Usually for air-coupled NDT
      & E purposes the lowest zero-order antisymmetric Lamb wave mode A0 is used,
      because it is most sensitive to internal defects and thickness variations. The
      velocity of the A0 mode is reduced with a reducing frequency and at low
      frequencies may become slower than the ultrasound velocity in air. Such a wave is
      named a slow Lamb wave. The objective of this research was the development and
      investigation of an air-coupled excitation method of the slow zero-order
      antisymmetric Lamb wave based on application of a piezoceramic ultrasonic array.
      We have proposed to excite the A0 mode by a planar air-coupled phased array with
      rectangular elements. The array is matched to the wavelength of the A0 mode in
      the film. Performance of such an excitation method was investigated both
      theoretically and experimentally. Two excitation methods of the array were
      analysed: when all array elements were excited simultaneously or one by one with
      a proper delay. In order to reduce crosstalk between array elements via the air
      gap, we have proposed an optimization procedure based on additional shifts of
      electric excitation impulses of the array elements. For experimental verification
      of the proposed approach a prototype of the air-coupled eight element array made
      of Pz-29 piezoceramic strips was manufactured. Experimental validation confirmed
      the possibility of exciting the slow A0 Lamb wave mode through the air gap in
      thin plates and films.

PMID- 30103508
TI  - Contribution of Local Analysis Techniques for the Characterization of Iron and
      Alloying Elements in Nitrides: Consequences on the Precipitation Process in Fe-Si
      and Fe-Cr Nitrided Alloys.
AB  - Atom Probe Tomography (APT), Transmission Electron Microscopy (TEM), and 3D
      mechanical calculations in complex geometry and anisotropic strain fields were
      employed to study the role of minor elements in the precipitation process of
      silicon and chromium nitrides in nitrided Fe-Si and Fe-Cr alloys, respectively.
      In nitrided Fe-Si alloys, an original sequence of Si3N4 precipitation was
      highlighted. Al-N clusters form first and act as nucleation sites for amorphous
      Si3N4 nitrides. This novel example of particle-simulated nucleation opens a new
      way to control Si3N4 precipitation in Fe-Si alloys. In nitrided Fe-Cr alloys,
      both the presence of iron in chromium nitrides and excess nitrogen in the
      ferritic matrix are unquestionably proved. Only a certain part of the so-called
      excess nitrogen is shown to be explained by the elastic accommodation of the
      misfit between nitride and the ferritic matrix. The presence of immobile excess
      nitrogen trapped at interfaces can be highly suspected.

PMID- 30103511
TI  - Calcined Mussel Shell Powder (CMSP) via Modification with Surfactants:
      Application for Antistatic Oil-Removal.
AB  - Biomass is known to efficiently adsorb pollutants from wastewater. In this paper,
      we demonstrated that a new antistatic oil-cleaning material can be prepared and
      assembled by using two surfactants, alkyl polyglucosides (APG) and dimethyl
      octadecyl hydroxy ethyl ammonium nitrate (SN), to modify calcined mussel shell
      powder (CMSP) through a two-step hydrotherm-assisted adsorption. The pore size
      and structure of CMSP was measured by BET and a contact angle meter was used to
      characterize the surface wetting ability. XRD, FTIR, XPS, SEM, TEM, and HRTEM
      were employed to determine the surface structure of CMSP modified by surfactants
      APG and SN (MMO). In order to further characterize properties of the surface
      morphology and crystal structure, the HRTEM was employed to show that the MMO
      surface had a single crystal structure: calcite, with a crystal plane spacing of
      0.2467 nm. The surface of MMO appeared to be fluffy and disperse. The antistatic
      and degreasing ability of as-prepared samples (MMO) was evaluated by a ZC-36 high
      resistance meter and BD-457 whiteness meter. The results showed that when the
      calcination temperature of CMSP reached 1000  degrees C, and the addition amount
      of APG and SN was 0.8 g and 0.16 g, it had an optimum antistatic effect with a
      surface resistivity (Rs) of 1.35 * 108 Omega, and a detergency rate to oil of
      17.35%. This study aims to embrace a green solution to reduce environmental
      pressure and make use of waste, which is of great significance to environmental
      protection.

PMID- 30103509
TI  - Effects of Adherence to a Higher Protein Diet on Weight Loss, Markers of Health,
      and Functional Capacity in Older Women Participating in a Resistance-Based
      Exercise Program.
AB  - Resistance training and maintenance of a higher protein diet have been
      recommended to help older individuals maintain muscle mass. This study examined
      whether adherence to a higher protein diet while participating in a resistance
      based exercise program promoted more favorable changes in body composition,
      markers of health, and/or functional capacity in older females in comparison to
      following a traditional higher carbohydrate diet or exercise training alone with
      no diet intervention. In total, 54 overweight and obese females (65.9 +/- 4.7
      years; 78.7 +/- 11 kg, 30.5 +/- 4.1 kg/m2, 43.5 +/- 3.6% fat) were randomly
      assigned to an exercise-only group (E), an exercise plus hypo-energetic higher
      carbohydrate (HC) diet, or a higher protein diet (HP) diet. Participants followed
      their respective diet plans and performed a supervised 30-min circuit-style
      resistance exercise program 3 d/wk. Participants were tested at 0, 10, and 14
      weeks. Data were analyzed using univariate, multivariate, and repeated measures
      general linear model (GLM) statistics as well as one-way analysis of variance
      (ANOVA) of changes from baseline with [95% confidence intervals]. Results
      revealed that after 14 weeks, participants in the HP group experienced
      significantly greater reductions in weight (E -1.3 +/- 2.3, [-2.4, -0.2]; HC -3.0
      +/- 3.1 [-4.5, -1.5]; HP -4.8 +/- 3.2, [-6.4, -3.1]%, p = 0.003), fat mass (E 
      2.7 +/- 3.8, [-4.6, -0.9]; HC -5.9 +/- 4.2 [-8.0, -3.9]; HP -10.2 +/- 5.8 [-13.2,
      -7.2%], p < 0.001), and body fat percentage (E -2.0 +/- 3.5 [-3.7, -0.3]; HC -4.3
      +/- 3.2 [-5.9, -2.8]; HP -6.3 +/- 3.5 [-8.1, -4.5] %, p = 0.002) with no
      significant reductions in fat-free mass or resting energy expenditure over time
      or among groups. Significant differences were observed in leptin (E -1.8 +/- 34 [
      18, 14]; HC 43.8 +/- 55 [CI 16, 71]; HP -26.5 +/- 70 [-63, -9.6] ng/mL, p =
      0.001) and adiponectin (E 43.1 +/- 76.2 [6.3, 79.8]; HC -27.9 +/- 33.4 [-44.5, 
      11.3]; HP 52.3 +/- 79 [11.9, 92.8] ug/mL, p = 0.001). All groups experienced
      significant improvements in muscular strength, muscular endurance, aerobic
      capacity, markers of balance and functional capacity, and several markers of
      health. These findings indicate that a higher protein diet while participating in
      a resistance-based exercise program promoted more favorable changes in body
      composition compared to a higher carbohydrate diet in older females.

PMID- 30103512
TI  - Reliability of 3D Lower Extremity Movement Analysis by Means of Inertial Sensor
      Technology during Transitional Tasks.
AB  - This study assesses the reliability and agreement of trunk and lower limb joints'
      3D kinematics, measured by inertial measurement units, during walking and more
      demanding movement tasks. For data analysis, tasks were divided in open and
      closed chain phases. Twenty healthy participants were included. On day one,
      measurements were conducted by "Operator 1" and "Operator 2" to determine between
      operator reliability/agreement. On day two, the measurements were conducted by
      Operator 1, in order to determine within-session reliability/agreement.
      Furthermore, between-session reliability/agreement was assessed based on data
      from Operator 1, captured on day one and two. Within-session
      reliability/agreement was high, and better than between-session and between
      operator results for all tasks. The results for walking were generally better
      than for other movement tasks, for all joint kinematics, and for both open and
      closed chain phases. Only for the ab/adduction and flexion/extension angles
      during forward and sideward lunge, reliability and agreement results were
      comparable to walking, for both the open and closed chain phases. The fact that
      lunges show similar reliability results than walking for open and closed chain
      phases, but require more motor control to perform, indicates that the performance
      of lunges might be interesting to use in further research aiming to identify
      kinematic differences between populations.

PMID- 30103510
TI  - Antioxidant Activity of Myrtus communis L. and Myrtus nivellei Batt. & Trab.
      Extracts: A Brief Review.
AB  - Myrtus communis L. (myrtle) and Myrtus nivellei Batt. & Trab. (Saharan myrtle)
      have been used in folk medicine for alleviating some ailments. M. communis is
      largely distributed in the Mediterranean Basin, whereas M. nivellei is confined
      in specific zones of the central Saharan mountains. The chemical composition and
      antioxidant activity of berry and leaf extracts isolated from myrtle are deeply
      documented, whereas those isolated from Saharan myrtle extracts are less studied.
      In both species, the major groups of constituents include gallic acid
      derivatives, flavonols, flavonol derivatives, and hydroxybenzoic acids. In
      coloured berries, anthocyanins are also present. In M. nivellei extracts are
      reported for some compounds not described in M. communis so far: 2-hydroxy-1,8
      cineole-beta-d-glucopyranoside, 2-hydroxy-1,8-cineole 2-O-alpha-l
      arabinofuranosyl (1->6)-beta-d-glucopyranoside, rugosin A, and rugosin B. Berries
      and leaves extracts of both species had antioxidant activity. Comparative studies
      of the antioxidant activity between leaf and berry myrtle extracts revealed that
      leaf extracts are best antioxidants, which can be assigned to the galloyl
      derivatives, flavonols, and flavonols derivatives, although the ratio of these
      groups of compounds might also have an important role in the antioxidant
      activity. The anthocyanins present in myrtle berries seem to possess weak
      antioxidant activity. The antioxidant activity of sample extracts depended on
      various factors: harvesting time, storage, extraction solvent, extraction type,
      and plant part used, among other factors. Leaf extracts of myrtle revealed to
      possess anti-inflammatory activity in several models used. This property has been
      attributed either to the flavonoids and/or hydrolysable tannins, nevertheless
      nonprenylated acylphloroglucinols (e.g., myrtucommulone and semimyrtucommulone)
      have also revealed a remarkable role in that activity. The biological activities
      of myrtle extracts found so far may direct its use towards for stabilizing
      complex lipid systems, as prebiotic in food formulations, and as novel
      therapeutic for the management of inflammation.

PMID- 30103513
TI  - Surface-Attached Poly(oxanorbornene) Hydrogels with Antimicrobial and Protein
      Repellent Moieties: The Quest for Simultaneous Dual Activity.
AB  - By copolymerizing an amphiphilic oxanorbornene monomer bearing N- tert
      butyloxycarbonyl (Boc) protected cationic groups with an oxanorbornene
      functionalized poly(ethylene glycol) (PEG) macromonomer, bifunctional comb
      copolymers were obtained. Varying the comonomer ratios led to copolymers with PEG
      contents between 5-25 mol %. These polymers were simultaneously surface
      immobilized on benzophenone-bearing substrates and cross-linked with
      pentaerythritoltetrakis(3-mercaptopropionate). They were then immersed into HCl
      to remove the Boc groups. The thus obtained surface-attached polymer hydrogels
      (called SMAMP*-co-PEG) were simultaneously antimicrobial and protein-repellent.
      Physical characterization data showed that the substrates used were homogeneously
      covered with the SMAMP*-co-PEG polymer, and that the PEG moieties tended to
      segregate to the polymer-air interface. Thus, with increasing PEG content, the
      interface became increasingly hydrophilic and protein-repellent, as demonstrated
      by a protein adhesion assay. With 25 mol % PEG, near-quantitative protein
      adhesion was observed. The antimicrobial activity of the SMAMP*-co-PEG polymers
      originates from the electrostatic interaction of the cationic groups with the
      negatively charged cell envelope of the bacteria. However, the SMAMP*-co-PEG
      surfaces were only fully active against E. coli, while their activity against S.
      aureus was already compromised by as little as 5 mol % (18.8 mass %) PEG. The
      long PEG chains seem to prevent the close interaction of bacteria with the
      surface, and also might reduce the surface charge density.

PMID- 30103514
TI  - Detailed Assessment of the Spatial Distribution of Urban Parks According to Day
      and Travel Mode Based on Web Mapping API: A Case Study of Main Parks in Wuhan.
AB  - This article employs two indexes-accessibility and effective service ratio (ESR)
      to assess the spatial distribution of urban parks with the consideration of both
      equity and efficiency. Traditional approaches to calculate these two indexes are
      often based on the shortest distance to the park within its service radius by
      network analysis. Such approaches cannot reflect the actual travel behaviors of
      urban residents and require extensive data collection of road networks and
      complex parameter setting. To avoid these defects, this study directly acquires
      travel time data for various travel modes in a specific time period to the park
      through web mapping API (Application Program Interface), then calculates the
      accessibility and ESR of urban parks based on these detailed data. This method
      gets closer to actual park usage situation and avoids the cumbersome process of
      road network model building. At last, a case study is conducted on the assessment
      of spatial distribution of main parks in Wuhan, finding that districts with poor
      park accessibility in Wuhan can be divided into three types: districts with an
      absence of parks, districts with an insufficiency with parks, and districts
      separated from parks by traffic. Then, pertinent improvement suggestions are
      proposed, which provide some bases for decisions on future park planning and
      construction.

PMID- 30103515
TI  - Differential Effects of High Sugar, High Lard or a Combination of Both on
      Nutritional, Hormonal and Cardiovascular Metabolic Profiles of Rodents.
AB  - BACKGROUND: Dietary interventions in rodents can induce an excess of adipose
      tissue and metabolic disorders that resemble human obesity. Nevertheless, these
      approaches are not standardized, and the phenotypes may vary distinctly among
      studies. The aim of this study was to investigate the effects of different
      dietary interventions on nutritional, metabolic, biochemical, hormonal, and
      cardiovascular profiles, as well as to add to development and characterization of
      an experimental model of obesity. METHODS: Male Wistar rats were randomized into
      four groups: control diet (C), high-sugar (HS), high-fat (HF), or high-sugar and
      high-fat (HFHS). Weekly measurements of body weight, adiposity, area under the
      curve (AUC) for glucose, blood pressure (BP) and serum triglycerides, total
      cholesterol level, and leptin were performed. RESULTS: HF and HFHS models were
      led to obesity by increases in adipose tissue deposition and the adiposity index.
      All hypercaloric diets presented systolic BP increases. In addition, the AUC for
      glucose was greater in HF and HFHS than in C, and only the HF group presented
      hyperleptinemia. CONCLUSIONS: HF and HFHS diet approaches promote obesity and
      comorbidities, and thus represent a useful tool for studying human obesity
      related disorders. By contrast, the HS model did not prove to be a good model of
      obesity.

PMID- 30103516
TI  - Hydrogen Sulfide-Releasing Fibrous Membranes: Potential Patches for Stimulating
      Human Stem Cells Proliferation and Viability under Oxidative Stress.
AB  - The design of biomaterial platforms able to release bioactive molecules is
      mandatory in tissue repair and regenerative medicine. In this context,
      electrospinning is a user-friendly, versatile and low-cost technique, able to
      process different kinds of materials in micro- and nano-fibers with a large
      surface area-to-volume ratio for an optimal release of gaseous signaling
      molecules. Recently, the antioxidant and anti-inflammatory properties of the
      endogenous gasotramsmitter hydrogen sulfide (H2S), as well as its ability to
      stimulate relevant biochemical processes on the growth of mesenchymal stem cells
      (MSC), have been investigated. Therefore, in this work, new poly(lactic) acid
      fibrous membranes (PFM), doped and functionalized with H2S slow-releasing donors
      extracted from garlic, were synthetized. These innovative H2S-releasing mats were
      characterized for their morphological, thermal, mechanical, and biological
      properties. Their antimicrobial activity and effects on the in vitro human
      cardiac MSC growth, either in the presence or in the absence of oxidative stress,
      were here assessed. On the basis of the results here presented, these new H2S
      releasing PFM could represent promising and low-cost scaffolds or patches for
      biomedical applications in tissue repair.

PMID- 30103518
TI  - Ruthenium on Carbonaceous Materials for the Selective Hydrogenation of HMF.
AB  - We report the use of Ru catalysts supported in the activated carbon (AC) and
      carbon nanofibers (CNFs) for the selective production of liquid fuel
      dimethylfuran (DMF) and fuel additives alkoxymethyl furfurals (AMF). Parameters
      such as the reaction temperature and hydrogen pressure were firstly investigated
      in order to optimise the synthesis of the desired products. Simply by using a
      different support, the selectivity of the reaction drastically changed. DMF was
      produced with AC as support, while a high amount of AMF was produced when CNFs
      were employed. Moreover, the reusability of the catalysts was tested and
      deactivation phenomena were identified and properly addressed. Further studies
      need to be performed in order to optimise the stability of the catalysts.

PMID- 30103517
TI  - Neurite Growth and Polarization on Vitronectin Substrate after in Vitro Trauma is
      not Enhanced after IGF Treatment.
AB  - Following traumatic brain injuries (TBI), insulin-like growth factor (IGF) is
      cortically widely upregulated. This upregulation has a potential role in the
      recovery of neuronal tissue, plasticity, and neurotrophic activity, though the
      molecular mechanisms involved in IGF regulation and the exact role of IGF after
      TBI remain unclear. Vitronectin (VN), an extracellular matrix (ECM) molecule, has
      recently been shown to be of importance for IGF-mediated cellular growth and
      migration. Since VN is downregulated after TBI, we hypothesized that insufficient
      VN levels after TBI impairs the potential beneficial activity of IGF. To test if
      vitronectin and IGF-1/IGFBP-2 could contribute to neurite growth, we cultured
      hippocampal neurons on +/- vitronectin-coated coverslips and them treated with +/
      IGF-1/IGF binding protein 2 (IGFBP-2). Under same conditions, cell cultures were
      also subjected to in vitro trauma to investigate differences in the posttraumatic
      regenerative capacity with +/- vitronectin-coated coverslips and with +/- IGF
      1/IGFBP-2 treatment. In both the control and trauma situations, hippocampal
      neurons showed a stronger growth pattern on vitronectin than on the control
      substrate. Surprisingly, the addition of IGF-1/IGFBP-2 showed a decrease in
      neurite growth. Since neurite growth was measured as the number of neurites per
      area, we hypothesized that IGF-1/IGFBP-2 contributes to the polarization of
      neurons and thus induced a less dense neurite network after IGF-1/IGFBP-2
      treatment. This hypothesis could not be confirmed and we therefore conclude that
      vitronectin has a positive effect on neurite growth in vitro both under normal
      conditions and after trauma, but that addition of IGF-1/IGFBP-2 does not have a
      positive additive effect.

PMID- 30103520
TI  - Microwave-Assisted Rapid Preparation of Nano-ZnO/Ag Composite Functionalized
      Polyester Nonwoven Membrane for Improving Its UV Shielding and Antibacterial
      Properties.
AB  - The cost and efficiency of preparing ZnO/Ag composite functional polyester
      membrane affect their application, for which a rapid microwave-assisted method
      was studied for coating ZnO/Ag composite nanoparticles on polyester nonwoven. The
      surface morphology, crystalline structure, and surface chemistry of the uncoated
      and coated polyester nonwoven was investigated by X-ray diffractometer (XRD),
      scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT
      IR), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy
      (XPS), and thermogravimetric (TG), respectively. Washing stability, ultraviolet
      properties, and antibacterial properties of before and after treatment polyester
      nonwoven were also investigated. The results indicated that Ag/ZnO composite
      nanoparticles were successfully deposited on polyester nonwoven surface. The
      amount of silver nitrate added in reaction has an important effect on the
      morphology and structure of Ag/ZnO composite on the surface of polyester fiber.
      The washing experiment results show that the ZnO/Ag composite functional
      polyester nonwoven fabric prepared by this method exhibits good washing
      durability after 90 min of washing. The results of UV transmission analysis
      showed that polyester nonwoven has an obvious increase in ultraviolet resistant
      properties after Ag/ZnO composite coating. When 0.2 g of silver nitrate was added
      into 100 mL of the reaction solution, the mean ultraviolet protection factor
      (UPF) of the treated polyester nonwoven reached a maximum of 219.8. The
      antibacterial results showed that the coated nonwoven against Escherichia coli
      and Staphylococcus aureus was about 94.5% and 96.6%, respectively, showing very
      good antibacterial properties.

PMID- 30103519
TI  - A Systematic Review on Materno-Foetal Outcomes in Pregnant Women with IgA
      Nephropathy: A Case of "Late-Maternal" Preeclampsia?
AB  - BACKGROUND: IgA nephropathy is the most common primary glomerulonephritis in
      pregnancy and shares with other immunologic diseases and kidney diseases a
      relationship with adverse maternal outcomes, whose entity and pattern is only
      partially quantified. Recent studies provide new information and a systematic
      review regarded progression of kidney disease. The discussion of the outcomes
      with respect to low-risk pregnancies may help to perfect the estimation of the
      risks, and to identify specific research needs. METHODS: A search strategy was
      built on Medline, EMBASE and the Cochrane review for the period January 2000
      April 2017, aimed at retrieving both case series (defined as with at least 6
      pregnancies in women with IgA nephropathy) and case reports, to look into rare
      occurrences. All papers, with or without control groups, were selected if they
      reported on at least one pregnancy outcome, or on long-term kidney function.
      Search strategy, paper selection and data extraction were done in duplicate
      (PROSPERO N 42016042623). Meta-analysis of case series was performed with
      Metanalyst Beta 3.13. Case reports were analysed narratively. RESULTS: The search
      retrieved 556 papers, of which 27 were included (13 series and 14 case-reports).
      The case series report on 581 women with 729 pregnancies. The analysis was
      performed in comparison to the available control groups: 562 non-pregnant
      controls were available for the analysis of progression of kidney disease. As for
      pregnancy related outcomes (preeclampsia (PE), pregnancy induced hypertension
      (PIH), preterm birth, small babies), we meta-analyzed the data with respect to
      the only series of low-risk pregnancies (1418 pregnancies). When compared with
      women who never got pregnant after diagnosis of IgA nephropathy, in the present
      meta-analysis pregnancy in women with IgA nephropathy was not associated with a
      higher risk of progression of kidney disease, possibly due to the overall
      preserved kidney function at baseline: end-stage kidney disease (OR 0.68; CI 0.28
      1.65). Conversely, the incidence of adverse pregnancy-related outcomes was
      increased compared to low-risk controls: PE and PIH were more than ten-fold
      increased (OR 11.80; CI 7.53-18.48 and OR 10.39; CI 5.45-19.80), while the
      increase in risk of preterm birth and "low birth weight babies" was less marked
      (OR 3.37; CI 1.91-5.95 and OR 2.36; CI 1.52-3.66), a discrepancy suggesting the
      occurrence of "late" or "maternal" PE, that may affect less severely foetal
      growth or shorten gestation. In conclusion, in the present meta-analysis IgA
      nephropathy was not associated with an increased progression of kidney disease.
      The more than ten-fold increased risk of PIH and PE, in combination with a
      doubled risk of small babies, suggests the occurrence of "late" or "maternal" PE,
      usually less affecting early foetal growth. This finding may be of help in
      defining control policies, while further research is needed to guide clinical
      management.

PMID- 30103521
TI  - A New Method for Recognizing Cytokines Based on Feature Combination and a Support
      Vector Machine Classifier.
AB  - Research on cytokine recognition is of great significance in the medical field
      due to the fact cytokines benefit the diagnosis and treatment of diseases, but
      the current methods for cytokine recognition have many shortcomings, such as low
      sensitivity and low F-score. Therefore, this paper proposes a new method on the
      basis of feature combination. The features are extracted from compositions of
      amino acids, physicochemical properties, secondary structures, and evolutionary
      information. The classifier used in this paper is SVM. Experiments show that our
      method is better than other methods in terms of accuracy, sensitivity,
      specificity, F-score and Matthew's correlation coefficient.

PMID- 30103525
TI  - Exploring Semi-Supervised Methods for Labeling Support in Multimodal Datasets.
AB  - Working with multimodal datasets is a challenging task as it requires annotations
      which often are time consuming and difficult to acquire. This includes in
      particular video recordings which often need to be watched as a whole before they
      can be labeled. Additionally, other modalities like acceleration data are often
      recorded alongside a video. For that purpose, we created an annotation tool that
      enables to annotate datasets of video and inertial sensor data. In contrast to
      most existing approaches, we focus on semi-supervised labeling support to infer
      labels for the whole dataset. This means, after labeling a small set of instances
      our system is able to provide labeling recommendations. We aim to rely on the
      acceleration data of a wrist-worn sensor to support the labeling of a video
      recording. For that purpose, we apply template matching to identify time
      intervals of certain activities. We test our approach on three datasets, one
      containing warehouse picking activities, one consisting of activities of daily
      living and one about meal preparations. Our results show that the presented
      method is able to give hints to annotators about possible label candidates.

PMID- 30103524
TI  - Computational-Based Study of QuEChERS Extraction of Cyclohexanedione Herbicide
      Residues in Soil by Chemometric Modeling.
AB  - Assessment of two buffered QuEChERS (quick, easy, cheap, effective, rugged, and
      safe) versions (i.e., citrate and acetate) modified by including methanol to
      recover the residues of three cyclohexanedione oxime (CHD) herbicides and three
      of their byproducts from agricultural soil was performed. In this context, a full
      second-order face-centered factorial experimental design was developed to
      quantify the influences of the main five variables (i.e., extraction time, water
      content, soil weight, and extraction solvent volume and composition) on the
      target compound recoveries. The fitting equations satisfactorily described the
      extraction process behavior. The mathematical models also showed the most
      influencing independent variables (i.e., extraction solvent composition and soil
      weight). Handling simpler expressions was possible with the acetate QuEChERS but
      not with the citrate QuEChERS. The recoveries of the CHD residues were close to
      100% after performing the extraction under suitable conditions. Furthermore,
      dispersive solid-phase extraction (dSPE) clean-up steps were assessed to reduce
      the matrix effect in mass spectrometry. In this sense, the citrate QuEChERS in
      combination with the PSA + C18 clean-up step was the best option for the
      extraction of CHD residues.

PMID- 30103526
TI  - Impact of Mosquito Age and Insecticide Exposure on Susceptibility of Aedes
      albopictus (Diptera: Culicidae) to Infection with Zika Virus.
AB  - Zika virus (ZIKV) is primarily transmitted to humans by Aedes aegypti and Ae.
      albopictus. Vector-virus interactions influencing vector competence vary and
      depend on biological and environmental factors. A mosquito's chronological age
      may impact its immune response against virus infection. Insecticides, source
      reduction, and/or public education are currently the best defense against
      mosquitoes that transmit ZIKV. This study assessed the effects of a mosquito's
      chronological age at time of infection on its response to ZIKV infection. We
      exposed young (6-7 d post-emergence) and old (11-12 d post-emergence) Ae.
      albopictus to a sublethal dose of bifenthrin prior to oral exposure to blood
      meals containing ZIKV (7-day incubation period). Old mosquitoes experienced a
      significantly (p < 0.01) higher rate of mortality than young mosquitoes.
      Significantly higher ZIKV body titers (p < 0.01) were observed in the old control
      group compared to the young control group. Significantly higher (p < 0.01) ZIKV
      dissemination rates and leg titers (p < 0.01) were observed in old bifenthrin
      exposed mosquitoes compared to old control mosquitoes or young bifenthrin-exposed
      or control mosquitoes. Hence, bifenthrin exposure may increase the potential for
      virus transmission; however, the degree of these impacts varies with mosquito
      age. Impacts of insecticides should be considered in risk assessments of
      potential vector populations.

PMID- 30103523
TI  - Functional Genomics and Immunologic Tools: The Impact of Viral and Host Genetic
      Variations on the Outcome of Zika Virus Infection.
AB  - Zika virus (ZIKV) causes no-to-mild symptoms or severe neurological disorders. To
      investigate the importance of viral and host genetic variations in determining
      ZIKV infection outcomes, we created three full-length infectious cDNA clones as
      bacterial artificial chromosomes for each of three spatiotemporally distinct and
      genetically divergent ZIKVs: MR-766 (Uganda, 1947), P6-740 (Malaysia, 1966), and
      PRVABC-59 (Puerto Rico, 2015). Using the three molecularly cloned ZIKVs, together
      with 13 ZIKV region-specific polyclonal antibodies covering nearly the entire
      viral protein-coding region, we made three conceptual advances: (i) We created a
      comprehensive genome-wide portrait of ZIKV gene products and their related
      species, with several previously undescribed gene products identified in the case
      of all three molecularly cloned ZIKVs. (ii) We found that ZIKV has a broad cell
      tropism in vitro, being capable of establishing productive infection in 16 of 17
      animal cell lines from 12 different species, although its growth kinetics varied
      depending on both the specific virus strain and host cell line. More importantly,
      we identified one ZIKV-non-susceptible bovine cell line that has a block in viral
      entry but fully supports the subsequent post-entry steps. (iii) We showed that in
      mice, the three molecularly cloned ZIKVs differ in their neuropathogenicity,
      depending on the particular combination of viral and host genetic backgrounds, as
      well as in the presence or absence of type I/II interferon signaling. Overall,
      our findings demonstrate the impact of viral and host genetic variations on the
      replication kinetics and neuropathogenicity of ZIKV and provide multiple avenues
      for developing and testing medical countermeasures against ZIKV.

PMID- 30103527
TI  - On the Nature of Evidence and 'Proving' Causality: Smoking and Lung Cancer vs.
      Sun Exposure, Vitamin D and Multiple Sclerosis.
AB  - If environmental exposures are shown to cause an adverse health outcome, reducing
      exposure should reduce the disease risk. Links between exposures and outcomes are
      typically based on 'associations' derived from observational studies, and
      causality may not be clear. Randomized controlled trials to 'prove' causality are
      often not feasible or ethical. Here the history of evidence that tobacco smoking
      causes lung cancer-from observational studies-is compared to that of low sun
      exposure and/or low vitamin D status as causal risk factors for the autoimmune
      disease, multiple sclerosis (MS). Evidence derives from in vitro and animal
      studies, as well as ecological, case-control and cohort studies, in order of
      increasing strength. For smoking and lung cancer, the associations are strong,
      consistent, and biologically plausible-the evidence is coherent or 'in harmony'.
      For low sun exposure/vitamin D as risk factors for MS, the evidence is weaker,
      with smaller effect sizes, but coherent across a range of sources of evidence,
      and biologically plausible. The association is less direct-smoking is directly
      toxic and carcinogenic to the lung, but sun exposure/vitamin D modulate the
      immune system, which in turn may reduce the risk of immune attack on self
      proteins in the central nervous system. Opinion about whether there is sufficient
      evidence to conclude that low sun exposure/vitamin D increase the risk of
      multiple sclerosis, is divided. General public health advice to receive
      sufficient sun exposure to avoid vitamin D deficiency (<50 nmol/L) should also
      ensure any benefits for multiple sclerosis, but must be tempered against the risk
      of skin cancers.

PMID- 30103522
TI  - Modulation of Apoptosis by Cytotoxic Mediators and Cell-Survival Molecules in
      Sjogren's Syndrome.
AB  - The pathogenesis of Sjogren's syndrome (SS) involves multiple factors including
      genetic background, cell death, and exocrine dysfunction. We here discuss
      apoptotic control in exocrine glands in SS by showing various pro- and anti
      apoptotic pathways. Although the membrane-bound and soluble form of the Fas/Fas
      ligand system is a leading player with activation of the death domain and caspase
      8/3 cleavage, the role of soluble Fas/FasL (including its polymorphism) in
      apoptosis is controversial. The tumor necrosis factor related apoptosis-inducing
      ligand (TRAIL)-mediated apoptosis of salivary gland epithelial cells (SGECs)
      involves a mitochondrial pathway that includes caspase 9 cleavage. The
      involvement of innate immunity cells such as toll-like receptors (TLRs) has been
      investigated; TLR2-4 and TLR7-9 are associated with the induction of inflammation
      in exocrine glands of SS patients. TLR3 has the potential to induce the apoptosis
      of SS patients' SGECs. Linkage of epidermal growth factor (EGF) was shown in
      exocrine glands in SS, and it inhibited the Fas/FasL system with the help of cell
      survival factors. TLR3 has dual actions to cause inflammation as well as
      apoptosis, which are inhibited by EGF. In conclusion, apoptosis in exocrine
      glands of SS patients is tightly controlled by balance of pro-apoptotic signals
      and growth factor.

PMID- 30103528
TI  - Extracellular Water to Total Body Water Ratio in Viral Liver Diseases: A Study
      Using Bioimpedance Analysis.
AB  - AIMS: To investigate the relationship between extracellular water to total body
      water ratio (ECW/TBW) in bioimpedance analysis (BIA) and clinical parameters in
      hepatitis viruses related to liver diseases. METHODS: ECW/TBW was compared in
      patients with hepatitis B virus (HBV, n = 85) and hepatitis C virus (HCV, n =
      440) related liver diseases. We also examined factors linked to mild to severe
      overhydrated state (ECW/TBW >=0.4). RESULTS: The median ECW/TBW in the HCV group
      was 0.388 (range, 0.365-0.433), while that in the HBV group was 0.381 (range,
      0.363-0.425) (p < 0.0001). In all cases (n = 525), for predicting F3 or more,
      ECW/TBW yielded the area under the receiver operating characteristics (AUROC,
      0.74912) and for predicting F4, ECW/TBW yielded the AUROC (0.75517). Multivariate
      analysis showed that age, prothrombin time, serum albumin, and alanine
      aminotransferase were significant factors linked to ECW/TBW >=0.4. In patients
      with FIB-4 index <2, ECW/TBW in the HCV group was significantly higher than that
      in the HBV group (p = 0.0188), while in patients with 2 <= FIB-4 index <4 and FIB
      4 index >=4, the difference in the two groups did not reach significance.
      CONCLUSION: ECW/TBW can be different according to hepatitis viruses. Overhydrated
      status can easily occur in the HCV group even in the non-LC status compared with
      the HBV group.

PMID- 30103529
TI  - Acceptability and Utilization of Three Nutritional Supplements during Pregnancy:
      Findings from a Longitudinal, Mixed-Methods Study in Niger.
AB  - Nutritional status in pregnancy is a key determinant of birth outcomes. In low
      income countries, maternal diets are often limited, and daily nutrient
      supplements are recommended to fill nutrient gaps. As a result, it is important
      to understand the factors influencing acceptability and utilization of nutrient
      supplements in these settings. Qualitative data (individual interviews and focus
      group discussions with pregnant women, household members, and study staff) and
      quantitative data (unannounced household spot checks) were collected in 24
      villages in the Maradi region of south-central Niger. Each village was randomly
      assigned to one of three study arms, with pregnant women receiving either iron
      and folic acid (IFA) supplements, multiple micronutrient (MMN) supplements, or
      medium-quantity lipid-based nutrient supplements (MQ-LNS) for daily consumption
      during pregnancy. Data were collected longitudinally to capture changes in
      perspective as women progressed through their pregnancy. Participants accepted
      all three supplement types, and perceived a wide range of health benefits
      attributed to supplement consumption. However, several important barriers to
      appropriate consumption were reported, and rumors about the supplements leading
      to childbirth complications also decreased utilization. The household spot checks
      suggested that IFA had the highest level of correct consumption. Overall, despite
      a stated high level of acceptance and enthusiasm for the supplements among
      participants and their household members, certain fears, side effects, and
      organoleptic factors led to decreased utilization. The effectiveness of future
      programs to improve maternal nutritional status through supplementation may be
      improved by understanding perceived barriers and facilitating factors among
      participants and tailoring communication efforts appropriately.

PMID- 30103530
TI  - Academic Palliative Care Research in Portugal: Are We on the Right Track?
AB  - BACKGROUND: The narrow link between practice, education, and research is
      essential to palliative care development. In Portugal, academic postgraduate
      publications are the main booster for palliative care research. METHODS: This is
      a bibliometric study that aims to identify Portuguese palliative care
      postgraduate academic work published in electronic academic repositories between
      2000 and 2015. RESULTS: 488 publications were identified. The number of
      publications has increased, especially in the last five years. The most
      frequently used method was quantitative, healthcare professionals were the most
      studied participants, and psychological and psychiatric aspects of care comprised
      the most current theme. Practice-based priorities are financial costs and
      benefits of palliative care, awareness and understanding of palliative care,
      underserved populations, best practices, communication, and palliative care in
      nonhospital settings. CONCLUSION: The number of palliative care postgraduate
      academic publications has increased in Portugal in the past few years. There is
      academic production in the eight domains of quality palliative care and on the
      three levels of recommendation for practice-based research priorities. The major
      research gaps in Portugal are at the system and societal context levels.

PMID- 30103532
TI  - Fused Particle Fabrication 3-D Printing: Recycled Materials' Optimization and
      Mechanical Properties.
AB  - Fused particle fabrication (FPF) (or fused granular fabrication (FGF)) has
      potential for increasing recycled polymers in 3-D printing. Here, the open source
      Gigabot X is used to develop a new method to optimize FPF/FGF for recycled
      materials. Virgin polylactic acid (PLA) pellets and prints were analyzed and were
      then compared to four recycled polymers including the two most popular printing
      materials (PLA and acrylonitrile butadiene styrene (ABS)) as well as the two most
      common waste plastics (polyethylene terephthalate (PET) and polypropylene (PP)).
      The size characteristics of the various materials were quantified using digital
      image processing. Then, power and nozzle velocity matrices were used to optimize
      the print speed, and a print test was used to maximize the output for a two
      temperature stage extruder for a given polymer feedstock. ASTM type 4 tensile
      tests were used to determine the mechanical properties of each plastic when they
      were printed with a particle drive extruder system and were compared with
      filament printing. The results showed that the Gigabot X can print materials 6.5*
      to 13* faster than conventional printers depending on the material, with no
      significant reduction in the mechanical properties. It was concluded that the
      Gigabot X and similar FPF/FGF printers can utilize a wide range of recycled
      polymer materials with minimal post processing.

PMID- 30103531
TI  - Bacillus clausii for the Treatment of Acute Diarrhea in Children: A Systematic
      Review and Meta-Analysis of Randomized Controlled Trials.
AB  - Acute diarrhea is a burdensome disease with potentially harmful consequences,
      especially in childhood. Despite its large use in clinical practice, the efficacy
      of the probiotic Bacillus clausii in treating acute childhood diarrhea remains
      unclear. Our objective was to systematically review the efficacy of Bacillus
      clausii in the treatment of acute childhood diarrhea. The following electronic
      databases were systematically searched up to October 2017: MEDLINE (via
      PubMed/OVID), EMBASE (via OVID), Cochrane Central Database of Controlled Trials
      (via CENTRAL), Google Scholar, and ClinicalTrials.gov. Only randomized controlled
      trials were included. The overall effect for the meta-analysis was derived by
      using a random effects model. Six randomized controlled trials (1298 patients)
      met the eligibility criteria. Data arising from pooled analysis showed that
      Bacillus clausii significantly reduced the duration of diarrhea (mean difference
      = -9.12 h; 95% confidence interval [CI]: -16.49 to -1.75, p = 0.015), and the
      duration of hospitalization (mean difference = -0.85 days; 95% CI: -1.56 to 
      0.15, p = 0.017), compared with control. There was a trend of decreasing stool
      frequency after Bacillus clausii administration compared with the control group
      (mean difference = -0.19 diarrheal motions; 95% CI: -0.43 to -0.06, p = 0.14).
      Bacillus clausii may represent an effective therapeutic option in acute childhood
      diarrhea, with a good safety profile.

PMID- 30103533
TI  - Importance of Behavioral Therapy in Patients Hospitalized for Post-Traumatic
      Stress Disorder (PTSD) with Opioid Use Disorder.
AB  - Objective: To analyze differences in demographic pattern and hospitalization
      outcomes in post-traumatic stress disorder (PTSD) with opioid use disorder (OUD)
      patients managed with versus without behavioral therapy (BT). Methods: We
      conducted case-control study using Nationwide Inpatient Sample and identified
      PTSD and OUD using ICD-9-CM codes. Linear regression model was used to evaluate
      impact of BT on inpatient stay and cost. Results: We analyzed 1531 inpatient
      admissions and 786 patients received BT. Females had higher odds of receiving BT
      during inpatient management for PTSD with OUD (OR 1.210; 95% CI 1.020-1.436).
      About 63.1% patients receiving BT were benefited by Medicaid. Patients receiving
      BT had an increase in hospital stay by 1.27 days (P = 0.085) and hospitalization
      cost by $4734 (P = 0.018). There were no transfers to short term hospitals and
      lower transfers to skilled nursing facility (3.8% vs. 10.1%) in patients
      receiving BT. Conclusion: This study aims to reinforce combination management
      with psychotropic medications and BT in PTSD patients with comorbid OUD during
      hospitalization as it significantly decreases adverse disposition of the patient
      and thereby improves the quality of life post-treatment.

PMID- 30103534
TI  - A Review of Knowledge, Belief and Practice Regarding Osteoporosis among
      Adolescents and Young Adults.
AB  - Osteoporosis is a major public health problem affecting millions of people
      worldwide. Increasing knowledge, correcting health belief and promoting
      osteoprotective practices are effective measures for building and maintaining
      strong bone throughout ones' life-span. This review aims to summarize the
      contemporary evidence on the knowledge, beliefs and practice of adolescents and
      young adults on bone health. We performed literature searches using the PubMed
      and Scopus databases to identify original studies from 2008 to May 2018 using the
      search terms "(knowledge OR beliefs OR attitude OR practice OR behaviours OR
      physical activity OR exercise OR diet OR nutrition) AND (young OR youth OR
      adolescents OR children OR young adults OR students OR teenager) AND
      (osteoporosis OR bone health)". Of the 3206 articles found, 34 met the inclusion
      criteria. Studies showed that most adolescents and young adults had poor
      knowledge and expressed disinterest in osteoporosis. They believed that other
      diseases were more serious than osteoporosis, contributing to low perceived
      susceptibility and seriousness towards this disease. Popular media emerged as a
      platform to obtain information regarding osteoporosis. The lack of knowledge and
      misconceptions about osteoporosis led to poor osteoprotective practices. As a
      conclusion, the current evidence revealed a lack of awareness about osteoporosis
      among adolescents and young adults. Educational interventions may be useful to
      improve the awareness of osteoporosis among this population.

PMID- 30103535
TI  - Influence of Physical Activity on Bone Mineral Content and Density in Overweight
      and Obese Children with Low Adherence to the Mediterranean Dietary Pattern.
AB  - The objective of the present cross-sectional study was to examine the
      associations of physical activity and the adherence to the Mediterranean dietary
      pattern (MDP) with bone mineral content (BMC) and density (BMD) in children with
      overweight and obesity. A total of 177 (n = 80 girls) children with overweight
      and obesity aged 8 to 12 years old participated in the study. Both BMC and BMD
      were assessed by Dual-Energy X-ray absorptiometry. Dietary patterns were assessed
      by the KIDMED questionnaire and two 24-hour recalls. Physical activity was
      assessed by accelerometers for 7 consecutive days (24 hours/day). Low adherence
      to the MDP was observed in 82.4% of participants. Higher physical activity levels
      (of at least moderate intensity) and lower sedentary time were significantly
      associated with BMC and BMD in children with low adherence to the MDP (all p <
      0.05). No associations were observed between physical activity and BMC and BMD in
      children with high adherence to the MDP. In conclusion, engaging in moderate to
      vigorous physical activity and reducing the time spent in sedentary behavior
      might be particularly beneficial for improving bone health in overweight or obese
      children with poor adherence to the Mediterranean dietary pattern.

PMID- 30103537
TI  - Numerical-Experimental Study of the Consolidation Phenomenon in the Selective
      Laser Melting Process with a Thermo-Fluidic Coupled Model.
AB  - One of the main limiting factors for a widespread industrial use of the Selective
      Laser Melting Process it its lack of productivity, which restricts the use of
      this technology just for high added-value components. Typically, the thickness of
      the metallic powder that is used lies on the scale of micrometers. The use of a
      layer up to one millimeter would be necessarily associated to a dramatic increase
      of productivity. Nevertheless, when the layer thickness increases, the complexity
      of consolidation phenomena makes the process difficult to be governed. The
      present work proposes a 3D finite element thermo-coupled model to study the
      evolution from the metallic powder to the final consolidated material, analyzing
      specifically the movements and loads of the melt pool, and defining the behavior
      of some critical thermophysical properties as a function of temperature and the
      phase of the material. This model uses advanced numerical tools such as the
      Arbitrary Lagrangean-Eulerian formulation and the Automatic Remeshing technique.
      A series of experiments have been carried out, using a high thickness powder
      layer, allowing for a deeper understanding of the consolidation phenomena and
      providing a reference to compare the results of the numerical calculations.

PMID- 30103536
TI  - Force-Time Differences between Ballistic and Non-Ballistic Half-Squats.
AB  - The purpose of this study was to examine the force-time differences between
      concentric-only half-squats (COHS) performed with ballistic (BAL) or non
      ballistic (NBAL) intent across a range of loads. Eighteen resistance-trained men
      performed either BAL or NBAL COHS at 30%, 50%, 70%, and 90% of their one
      repetition maximum (1RM) COHS. Relative peak force (PF) and relative impulse from
      0-50 ms (Imp50), 0-90 ms (Imp90), 0-200 ms (Imp200), and 0-250 ms (Imp250) were
      compared using a series of 2 * 4 (intent * load) repeated measures ANOVAs with
      Bonferroni post hoc tests. Cohen's d effect sizes were calculated to provide
      measures of practical significance between the BAL and NBAL COHS and each load.
      BAL COHS produced statistically greater PF than NBAL COHS at 30% (d = 3.37), 50%
      (d = 2.88), 70% (d = 2.29), and 90% 1RM (d = 1.19) (all p < 0.001). Statistically
      significant main effect differences were found between load-averaged BAL and NBAL
      COHS for Imp90 (p = 0.006, d = 0.25), Imp200 (p = 0.001, d = 0.36), and Imp250 (p
      < 0.001, d = 0.41), but not for Imp50 (p = 0.018, d = 0.21). Considering the
      greater PF and impulse observed during the BAL condition, performing COHS with
      BAL intent may provide a favorable training stimulus compared to COHS performed
      with NBAL intent.

PMID- 30103539
TI  - Spatial Extension of Road Traffic Sensor Data with Artificial Neural Networks.
AB  - This paper proposes a method for estimating traffic flows on some links of a road
      network knowing the data on other links that are monitored with sensors. In this
      way, it is possible to obtain more information on traffic conditions without
      increasing the number of monitored links. The proposed method is based on
      artificial neural networks (ANNs), wherein the input data are the traffic flows
      on some monitored road links and the output data are the traffic flows on some
      unmonitored links. We have implemented and tested several single-layer feed
      forward ANNs that differ in the number of neurons and the method of generating
      datasets for training. The proposed ANNs were trained with a supervised learning
      approach where input and output example datasets were generated through traffic
      simulation techniques. The proposed method was tested on a real-scale network and
      gave very good results if the travel demand patterns were known and used for
      generating example datasets, and promising results if the demand patterns were
      not considered in the procedure. Numerical results have underlined that the ANNs
      with few neurons were more effective than the ones with many neurons in this
      specific problem.

PMID- 30103538
TI  - Functional Near-Infrared Spectroscopy Recordings of Visuospatial Working Memory
      Processes. Part II: A Replication Study in Children on Sensitivity and Mental
      Ability-Induced Differences in Functional Activation.
AB  - In a previous study in young adults, we showed that hemodynamic changes as
      measured by functional near-infrared spectroscopy (fNIRS) were sensitive for
      identifying visuospatial working memory (WM)-related functional brain activation
      in the prefrontal cortex. This functional activation, however, could not be
      verified for participants with far-above-average mental ability, suggesting
      different cognitive processes adopted by this group. The present study was
      designed to confirm these findings in 11- to 13-year-old children by applying the
      same study design, experimental task, fNIRS setup, and statistical approach. We
      successfully replicated the earlier findings on sensitivity of fNIRS with regard
      to visuospatial WM-specific task demands in our children sample. Likewise, mental
      ability-induced differences in functional activation were even more pronounced in
      the children compared with in the young adults. By testing a children sample, we
      were able to not only replicate our previous findings based on adult participants
      but also generalize the validity of these findings to children. This latter
      aspect seems to be of particular significance considering the relatively large
      number of fNIRS studies on WM performance in children.

PMID- 30103542
TI  - Therapeutic Vaccines for Genitourinary Malignancies.
AB  - The field of genitourinary malignancies has been a showcase for therapeutic
      cancer vaccine success since the application of intravesicular Bacillus Calmette
      Guerin (BCG) for bladder cancer in the 1970s and enjoyed a renaissance in 2010
      with the US Food and Drug Administration (FDA) approval of sipuleucel-T for
      prostate cancer. Several vaccine strategies have emerged, such as autologous or
      allogeneic whole-tumor vaccines, DNA vaccines, use of viral vectors, and peptides
      as immunostimulatory adjuvants. Despite impressive early trials, vaccine
      monotherapy has achieved limited success in the clinical world; however,
      combinations of vaccine and immune checkpoint inhibition or vaccine and cytokine
      stimulation are expected to move the field forward. This article reviews pivotal
      trials of cancer vaccines in prostate, renal, and bladder cancer and ongoing
      trials combining vaccines with other immune therapy agents.

PMID- 30103540
TI  - The Efficacy of Amifostine against Multiple-Dose Doxorubicin-Induced Toxicity in
      Rats.
AB  - Amifostine is well known cytoprotector which is efficient when administered
      before a wide range of antineoplastic agents. The aim of our study was to
      investigate amifostine effects on doxorubicin-induced toxic changes in rats.
      Amifostine (75 mg/kg ip) was given 30 min before each dose of doxorubicin
      (cumulatively 20 mg/kg ip, for 28 days). The animals' whole-body, liver, and
      kidney weight, serum biochemical examination, as well as microscopic examination
      of bone marrow, peripheral blood, liver, and kidney, were done on day 56 of the
      study. Hepatic and renal alterations were carefully quantified by
      semiquantitative grading scales-hepatic and renal damage score, respectively. In
      amifostine-pretreated rats, the number of peripheral blood leukocytes was
      significantly higher in comparison to doxorubicin-only treated group,
      preferentially protecting neutrophils. In the same group of rats, hepatic and
      renal alterations associated with polymorphonuclear cell infiltrates were
      significantly less severe than those observed in animals receiving only
      doxorubicin. Our results showed that amifostine successfully protected rats
      against multiple-dose doxorubicin-induced toxicity by complex, and still not
      fully elucidated mechanisms of action.

PMID- 30103543
TI  - Salivary Detection of Dengue Virus NS1 Protein with a Label-Free Immunosensor for
      Early Dengue Diagnosis.
AB  - Dengue virus (DENV) is a highly pathogenic, arthropod-borne virus transmitted
      between people by Aedes mosquitoes. Despite efforts to prevent global spread, the
      potential for DENV epidemics is increasing world-wide. Annually, 3.6 billion
      people are at risk of infection. With no licensed vaccine, early diagnosis of
      dengue infection is critical for clinical management and patient survival.
      Detection of DENV non-structural protein 1 (NS1) is a clinically accepted
      biomarker for the early detection of DENV infection. Unfortunately, virtually all
      of the laboratory and commercial DENV NS1 diagnostic methods require a blood draw
      for sample analysis, limiting point-of-care diagnostics and decreases patient
      willingness. Alternatively, NS1 in human saliva has been identified for the
      potential early diagnosis of DENV infection. The collection of saliva is simple,
      non-invasive, painless, and inexpensive, even by minimally trained personnel. In
      this study, we present a label-free chemiresistive immunosensor for the detection
      of the DENV NS1 protein utilizing a network of single-walled carbon nanotubes
      functionalized with anti-dengue NS1 monoclonal antibodies. NS1 was successfully
      detected in adulterated artificial human saliva over the range of clinically
      relevant concentrations with high sensitivity and selectivity. It has potential
      application in clinical diagnosis and the ease of collection allows for self
      testing, even within the home.

PMID- 30103541
TI  - The Vitamin K Metabolome in Chronic Kidney Disease.
AB  - The purpose of this review is to summarize the research to date on the impact of
      chronic kidney disease (CKD) on the vitamin K metabolome. Vitamin K-dependent
      proteins contribute to cardiovascular disease (CVD) prevention via the prevention
      of ectopic mineralization. Sub-clinical vitamin K deficiency is common in CKD
      patients, and evidence suggests that it may contribute to the CVD burden in this
      population. Research from animal models suggests that CKD alters tissue measures
      of the two predominant forms of vitamin K: KI and MK-4. The expression and/or
      activity of enzymes that regulate the recycling of vitamin K and the
      carboxylation of vitamin K-dependent proteins also appear to be altered in CKD.
      Evidence suggests that statins, a common pharmaceutical prescribed to CKD
      patients to prevent cardiovascular events, may impact the metabolism of vitamin K
      and therefore contribute to its relative inefficiency at preventing CVD in this
      population as kidney disease progresses. Human research on the tissue vitamin K
      metabolome in CKD patients is lacking.

PMID- 30103544
TI  - A Precisely Flow-Controlled Microfluidic System for Enhanced Pre-Osteoblastic
      Cell Response for Bone Tissue Engineering.
AB  - Bone tissue engineering provides advanced solutions to overcome the limitations
      of currently used therapies for bone reconstruction. Dynamic culturing of cell
      biomaterial constructs positively affects the cell proliferation and
      differentiation. In this study, we present a precisely flow-controlled
      microfluidic system employed for the investigation of bone-forming cell responses
      cultured on fibrous collagen matrices by applying two flow rates, 30 and 50
      MUL/min. We characterized the collagen substrates morphologically by means of
      scanning electron microscopy, investigated their viscoelastic properties, and
      evaluated the orientation, proliferation and osteogenic differentiation capacity
      of pre-osteoblastic cells cultured on them. The cells are oriented along the
      direction of the flow at both rates, in contrast to a random orientation observed
      under static culture conditions. The proliferation of cells after 7 days in
      culture was increased at both flow rates, with the flow rate of 50 MUL/min
      indicating a significant increase compared to the static culture. The alkaline
      phosphatase activity after 7 days increased at both flow rates, with the rate of
      30 MUL/min indicating a significant enhancement compared to static conditions.
      Our results demonstrate that precisely flow-controlled microfluidic cell culture
      provides tunable control of the cell microenvironment that directs cellular
      activities involved in bone regeneration.

PMID- 30103546
TI  - Adaptive Discrete Vector Field in Sensor Networks.
AB  - Homology groups are a prime tool for measuring the connectivity of a network, and
      their computation in a distributed and adaptive way is mandatory for their use in
      sensor networks. In this paper, we propose a solution based on the construction
      of an adaptive discrete vector field from where, thanks to the discrete Morse
      theory, the generators of the homology groups are extracted. The efficiency and
      the adaptability of our approach are tested against two applications: the
      detection and the localization of the holes in the coverage, and the selection of
      active sensors ensuring complete coverage.

PMID- 30103545
TI  - ATP as a Pathophysiologic Mediator of Bacteria-Host Crosstalk in the
      Gastrointestinal Tract.
AB  - Extracellular nucleotides, such as adenosine triphosphate (ATP), are released
      from host cells including nerve termini, immune cells, injured or dead cells, and
      the commensal bacteria that reside in the gut lumen. Extracellular ATP interacts
      with the host through purinergic receptors, and promotes intercellular and
      bacteria-host communication to maintain the tissue homeostasis. However, the
      release of massive concentrations of ATP into extracellular compartments
      initiates acute and chronic inflammatory responses through the activation of
      immunocompetent cells (e.g., T cells, macrophages, and mast cells). In this
      review, we focus on the functions of ATP as a pathophysiologic mediator that is
      required for the induction and resolution of inflammation and inter-species
      communication.

PMID- 30103547
TI  - A Bifunctional Anti-Amyloid Blocks Oxidative Stress and the Accumulation of
      Intraneuronal Amyloid-Beta.
AB  - There is growing recognition regarding the role of intracellular amyloid beta
      (Abeta) in the Alzheimer's disease process, which has been linked with aberrant
      signaling and the disruption of protein degradation mechanisms. Most notably,
      intraneuronal Abeta likely underlies the oxidative stress and mitochondrial
      dysfunction that have been identified as key elements of disease progression. In
      this study, we employed fluorescence imaging to explore the ability of a
      bifunctional small molecule to reduce aggregates of intracellular Abeta and
      attenuate oxidative stress. Structurally, this small molecule is comprised of a
      nitroxide spin label linked to an amyloidophilic fluorene and is known as spin
      labeled fluorene (SLF). The effect of the SLF on intracellular Abeta accumulation
      and oxidative stress was measured in MC65 cells, a human neuronal cell line with
      inducible expression of the amyloid precursor protein and in the N2a neuronal
      cell line treated with exogenous Abeta. Super-resolution microscopy imaging
      showed SLF decreases the accumulation of intracellular Abeta. Confocal microscopy
      imaging of MC65 cells treated with a reactive oxygen species (ROS)-sensitive dye
      demonstrated SLF significantly reduces the intracellular Abeta-induced ROS
      signal. In order to determine the contributions of the separate SLF moieties to
      these protective activities, experiments were also carried out on cells with
      nitroxides lacking the Abeta targeting domain or fluorene derivatives lacking the
      nitroxide functionality. The findings support a synergistic effect of SLF in
      counteracting both the conformational toxicity of both endogenous and exogenous
      Abeta, its promotion of ROS, and Abeta metabolism. Furthermore, these studies
      demonstrate an intimate link between ROS production and Abeta oligomer formation.

PMID- 30103551
TI  - Effects of the Ground Resolution and Thresholding on Crack Width Measurements.
AB  - When diagnosing the condition of a structure, it is necessary to measure the
      widths of any existing cracks in the structure. To ensure safety when relying on
      images of cracks, the selected imaging parameters and processing technology must
      be well understood. In this study, the effects of the ground sample distance and
      threshold values on the crack width measurement error are analyzed from a
      theoretical perspective. Here, the main source of such errors is assumed to be
      due to the mixed pixel phenomena in the left and right boundary pixels. Thus, a
      mathematical model is proposed in which the intensity changes in these pixels are
      computed via an equation. In addition, the relationship between the error and
      error probability distribution is represented with an equation based on the
      threshold values and mean error. Upon analysis, it was found that the threshold
      value that minimizes the error is at the mid-point between the background and
      foreground, and the probabilistic nature of the error indicates that it is
      theoretically possible to predict both the error and its probability
      distribution. The proposed model was validated using artificial images.

PMID- 30103550
TI  - Galfenol Thin Films and Nanowires.
AB  - Galfenol (Fe1-xGax, 10 < x < 40) may be the only smart material that can be made
      by electrochemical deposition which enables thick film and nanowire structures.
      This article reviews the deposition, characterization, and applications of
      Galfenol thin films and nanowires. Galfenol films have been made by sputter
      deposition as well as by electrochemical deposition, which can be difficult due
      to the insolubility of gallium. However, a stable process has been developed,
      using citrate complexing, a rotating disk electrode, Cu seed layers, and pulsed
      deposition. Galfenol thin films and nanowires have been characterized for crystal
      structures and magnetostriction both by our group and by collaborators. Films and
      nanowires have been shown to be largely polycrystalline, with magnetostrictions
      that are on the same order of magnitude as textured bulk Galfenol.
      Electrodeposited Galfenol films were made with epitaxial texture on GaAs.
      Galfenol nanowires have been made by electrodeposition into anodic aluminum oxide
      templates using similar parameters defined for films. Segmented nanowires of
      Galfenol/Cu have been made to provide engineered magnetic properties.
      Applications of Galfenol and other magnetic nanowires include microfluidic
      sensors, magnetic separation, cellular radio-frequency identification (RFID)
      tags, magnetic resonance imaging (MRI) contrast, and hyperthermia.

PMID- 30103549
TI  - A Systems Approach to Study Immuno- and Neuro-Modulatory Properties of Antiviral
      Agents.
AB  - There are dozens of approved, investigational and experimental antiviral agents.
      Many of these agents cause serious side effects, which can only be revealed after
      drug administration. Identification of the side effects prior to drug
      administration is challenging. Here we describe an ex vivo approach for studying
      immuno- and neuro-modulatory properties of antiviral agents, which may be
      associated with potential side effects of these therapeutics. The current
      approach combines drug toxicity/efficacy tests and transcriptomics, which is
      followed by mRNA, cytokine and metabolite profiling. We demonstrated the utility
      of this approach with several examples of antiviral agents. We also showed that
      the approach can utilize different immune stimuli and cell types. It can also
      include other omics techniques, such as genomics and epigenomics, to allow
      identification of individual markers associated with adverse reactions to
      antivirals with immuno- and neuro-modulatory properties.

PMID- 30103548
TI  - Prostanoid EP2 Receptors Are Up-Regulated in Human Pulmonary Arterial
      Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle
      Cells.
AB  - Prostacyclins are extensively used to treat pulmonary arterial hypertension
      (PAH), a life-threatening disease involving the progressive thickening of small
      pulmonary arteries. Although these agents are considered to act therapeutically
      via the prostanoid IP receptor, treprostinil is the only prostacyclin mimetic
      that potently binds to the prostanoid EP2 receptor, the role of which is unknown
      in PAH. We hypothesised that EP2 receptors contribute to the anti-proliferative
      effects of treprostinil in human pulmonary arterial smooth muscle cells (PASMCs),
      contrasting with selexipag, a non-prostanoid selective IP agonist. Human PASMCs
      from PAH patients were used to assess prostanoid receptor expression, cell
      proliferation, and cyclic adenosine monophosphate (cAMP) levels following the
      addition of agonists, antagonists or EP2 receptor small interfering RNAs
      (siRNAs). Immunohistochemical staining was performed in lung sections from
      control and PAH patients. We demonstrate using selective IP (RO1138452) and EP2
      (PF-04418948) antagonists that the anti-proliferative actions of treprostinil
      depend largely on EP2 receptors rather than IP receptors, unlike MRE-269
      (selexipag-active metabolite). Likewise, EP2 receptor knockdown selectively
      reduced the functional responses to treprostinil but not MRE-269. Furthermore,
      EP2 receptor levels were enhanced in human PASMCs and in lung sections from PAH
      patients compared to controls. Thus, EP2 receptors represent a novel therapeutic
      target for treprostinil, highlighting key pharmacological differences between
      prostacyclin mimetics used in PAH.

PMID- 30103552
TI  - Risk Reduction Behaviors Regarding PM2.5 Exposure among Outdoor Exercisers in the
      Nanjing Metropolitan Area, China.
AB  - Aims: This study aimed to describe risk reduction behaviors regarding ambient
      particulate matter with a diameter of 2.5 MUm or less (PM2.5) among outdoor
      exercisers and to explore potential factors influencing those behaviors in the
      urban area of Nanjing, China. Method: A cross-sectional convenience sample survey
      was conducted among 302 outdoor exercisers in May 2015. Descriptive analysis was
      used to describe demographics, outdoor physical activity patterns, knowledge of
      PM2.5 and risk reduction behaviors. Multivariate logistic regression analysis was
      then used to explore factors that influence the adoption of risk reduction
      behaviors. Results: The most common behavior to reduce PM2.5 exposure was
      minimizing the times for opening windows on hazy days (75.5%), and the least
      common one was using air purifiers (19.3%). Two thirds of respondents indicated
      that they wore face masks when going outside in the haze (59.5%), but only 13.6%
      of them would wear professional antismog face masks. Participants adopting risk
      reduction behaviors regarding PM2.5 exposure tended to be females, 50-60 year
      olds, those with higher levels of knowledge about PM2.5 and those who had
      children. Conclusions: These findings indicate the importance of improving
      knowledge about PM2.5 among outdoor exercisers. Educational interventions should
      also be necessary to guide the public to take appropriate precautionary measures
      when undertaking outdoor exercise in high PM2.5 pollution areas.

PMID- 30103553
TI  - Effect of Metallothionein-III on Mercury-Induced Chemokine Gene Expression.
AB  - Mercury compounds are known to cause central nervous system disorders; however
      the detailed molecular mechanisms of their actions remain unclear. Methylmercury
      increases the expression of several chemokine genes, specifically in the brain,
      while metallothionein-III (MT-III) has a protective role against various brain
      diseases. In this study, we investigated the involvement of MT-III in chemokine
      gene expression changes in response to methylmercury and mercury vapor in the
      cerebrum and cerebellum of wild-type mice and MT-III null mice. No difference in
      mercury concentration was observed between the wild-type mice and MT-III null
      mice in any brain tissue examined. The expression of Ccl3 in the cerebrum and of
      Cxcl10 in the cerebellum was increased by methylmercury in the MT-III null but
      not the wild-type mice. The expression of Ccl7 in the cerebellum was increased by
      mercury vapor in the MT-III null mice but not the wild-type mice. However, the
      expression of Ccl12 and Cxcl12 was increased in the cerebrum by methylmercury
      only in the wild-type mice and the expression of Ccl3 in the cerebellum was
      increased by mercury vapor only in the wild-type mice. These results indicate
      that MT-III does not affect mercury accumulation in the brain, but that it
      affects the expression of some chemokine genes in response to mercury compounds.

PMID- 30103556
TI  - The Recognition of Sweat Latent Fingerprints with Green-Emitting Carbon Dots.
AB  - The recognition of fingerprints has played an extremely important role in
      criminal investigations, due to its uniqueness. This paper reports on the
      recognition of sweat latent fingerprints using green-emitting, environment
      friendly carbon dots prepared with DL-malic acid and ethylenediamine, and the
      exploration of impacting factors in the development process of fingerprints. The
      experiments showed that better fingerprint images could be obtained when the
      latent fingerprints are developed in green-emitting carbon dots with pH 9 for 30
      min, at room temperature. The reported method was also effective for latent
      fingerprints on a variety of substrates, as well as for those water-immersed
      ones, where the developed fingerprint remained stable after long-term
      preservation. Furthermore, the fluorescent three-dimensional fingerprint image
      could provide direct and simple evidence on pressing habits. The objective of
      this paper was to present this method. The method may help to narrow the range of
      suspects during criminal investigations and in forensic science.

PMID- 30103554
TI  - Ecological Determinants of Sporotrichosis Etiological Agents.
AB  - Ecological determinants of sporotrichosis etiological agents remain poorly
      understood. For this reason, we performed explorations using local climate
      estimates to determine the temperature and humidity ranges of the environment
      where clinically relevant Sporothrix species occur and to identify what plant
      species are associated with them, using data collected from the published
      literature. We performed a literature search to identify all publications on
      environmental isolations of medically relevant species of Sporothrix in the
      PubMed, SCOPUS, and EMBASE databases. All those studies were included in the
      analysis where medically relevant species of Sporothrix have been isolated from
      soil samples, and described a specific geographical location that could be
      precisely georeferenced. We approximated temperature and humidity from local
      climate estimates, integrating geospatial data, temperature, and water vapor
      pressure from regions or provinces where medically relevant species of Sporothrix
      have been isolated from soil. Sporothrix spp. were more commonly isolated from
      soil of different regions or provinces of 16 countries. Most environmental
      isolates were identified as S. schenckii, whereas S. pallida, S. brasiliensis, S.
      globosa, and S. mexicana were rare. We estimate that medically relevant
      Sporothrix spp. grow in the soil at temperatures of 6.6  degrees C to 28.84 
      degrees C and 37.5% to 99.06% relative humidity. These findings indicate that
      sporotrichosis etiological agents grow in soil in ecological niches from soil
      with wide ranges of temperature and humidity, but they are also associated with a
      variety of plants, flowers, woody debris, reed leaves, corn stalks, leaves, and
      wood crumbs, potentially facilitating its establishment and proliferation in the
      environment.

PMID- 30103555
TI  - Novel 3-Methyl-2-alkylthio Benzothiazolyl-Based Ionic Liquids: Synthesis,
      Characterization, and Antibiotic Activity.
AB  - Three series of novel 3-methyl-2-alkylthio benzothiazolyl ionic liquids (ILs)
      were synthesized for the first time. After structural identification, their
      melting point, solubility, and thermostability together with antibiotic activity
      were determined successively. As a result, 3-methyl-2-alkylthio benzothiazolyl p
      toluene sulfonate was found to have the highest antibacterial activity among the
      three series of ILs. Meanwhile, it has a good solubility in water as well. On the
      basis of comprehensive comparison with similar compounds, the effect of cations
      and anions of these benzothiazolium ILs on typical physical properties together
      with antibiotic performance was explored and discussed, which is very beneficial
      to take the greatest advantage of their structural designability for various
      purposes. Furthermore, the experiment data preliminarily discovered the
      relationships of the structure-properties/activities of the above three kinds ILs
      to a certain extent, which can provide useful references for future research and
      for the potential application of these new ILs as surfactant antiseptics or
      agricultural chemicals.

PMID- 30103557
TI  - In Situ Stress Tensor Determination during Phase Transformation of a Metal Matrix
      Composite by High-Energy X-ray Diffraction.
AB  - In situ high-energy X-ray diffraction using a synchrotron source performed on a
      steel metal matrix composite reinforced by TiC allows the evolutions of internal
      stresses during cooling to be followed thanks to the development of a new
      original experimental device (a transportable radiation furnace with controlled
      rotation of the specimen). Using the device on a high-energy beamline during in
      situ thermal treatment, we were able to extract the evolution of the stress
      tensor components in all phases: austenite, TiC, and even during the martensitic
      phase transformation of the matrix.

PMID- 30103558
TI  - Geographical Environment Factors and Risk Mapping of Human Cystic Echinococcosis
      in Western China.
AB  - The study aimed to reveal the risk factors and predict the prevalence of human
      cystic echinococcosis (CE) in Western China. To do this, we analyzed county-wide
      data relating to the prevalence of human CE in seven provinces of Western China,
      along with associated human, natural geographical environmental data. We then
      used spatial analysis and multiple regression analysis to investigate the
      correlation between the prevalence of human CE and associated environmental
      factors and to create a risk map of the disease in the seven provinces. Our
      analysis showed that grassland area ratio and Tibetan population ratio were
      independent variables positively correlated with the prevalence of human CE and
      that gross domestic product (GDP) and land surface temperature (LST; Spring) were
      negative independent variables. We also created a predictive risk map of human CE
      that revealed that the high-risk areas were mainly located in the south of
      Qinghai, the Northwest of Sichuan and most of the Tibet Autonomous Region.
      Knowledge of the spatial distribution and risk factors associated with human CE
      could help to prevent and control echinococcosis in China.

PMID- 30103559
TI  - Copper Binding Features of Tropomyosin-Receptor-Kinase-A Fragment: Clue for
      Neurotrophic Factors and Metals Link.
AB  - The nerve growth factor (NGF) is a neurotrophin essential for the development and
      maintenance of neurons, whose activity is influenced by copper ions. The NGF
      protein exerts its action by binding to its specific receptor, TrkA. In this
      study, a specific domain of the TrkA receptor, region 58-64, was synthesized and
      its copper(II) complexes characterized by means of potentiometric and
      spectroscopic studies. The two vicinal histidine residues provide excellent metal
      anchoring sites and, at physiological pH, a complex with the involvement of the
      peptide backbone amide nitrogen is the predominant species. The TrkA peptide is
      competitive for metal binding with analogous peptides due to the N-terminal
      domain of NGF. These data provide cues for future exploration of the effect of
      metal ions on the activity of the NGF and its specific cellular receptor.

PMID- 30103561
TI  - An Efficient Sampling-Based Algorithms Using Active Learning and Manifold
      Learning for Multiple Unmanned Aerial Vehicle Task Allocation under Uncertainty.
AB  - This paper presents a sampling-based approximation for multiple unmanned aerial
      vehicle (UAV) task allocation under uncertainty. Our goal is to reduce the amount
      of calculations and improve the accuracy of the algorithm. For this purpose,
      Gaussian process regression models are constructed from an uncertainty parameter
      and task reward sample set, and this training set is iteratively refined by
      active learning and manifold learning. Firstly, a manifold learning method is
      used to screen samples, and a sparse graph is constructed to represent the
      distribution of all samples through a small number of samples. Then, multi-points
      sampling is introduced into the active learning method to obtain the training set
      from the sparse graph quickly and efficiently. This proposed hybrid sampling
      strategy could select a limited number of representative samples to construct the
      training set. Simulation analyses demonstrate that our sampling-based algorithm
      can effectively get a high-precision evaluation model of the impact of uncertain
      parameters on task reward.

PMID- 30103560
TI  - The Regulation and Function of the L-Type Amino Acid Transporter 1 (LAT1) in
      Cancer.
AB  - The progression of cancer is associated with increases in amino acid uptake by
      cancer cells. Upon their entry into cells through specific transporters,
      exogenous amino acids are used to synthesize proteins, nucleic acids and lipids
      and to generate ATP. The essential amino acid leucine is also important for
      maintaining cancer-associated signaling pathways. By upregulating amino acid
      transporters, cancer cells gain greater access to exogenous amino acids to
      support chronic proliferation, maintain metabolic pathways, and to enhance
      certain signal transduction pathways. Suppressing cancer growth by targeting
      amino acid transporters will require an in-depth understanding of how cancer
      cells acquire amino acids, in particular, the transporters involved and which
      cancer pathways are most sensitive to amino acid deprivation. L-Type Amino Acid
      Transporter 1 (LAT1) mediates the uptake of essential amino acids and its
      expression is upregulated during the progression of several cancers. We will
      review the upstream regulators of LAT1 and the downstream effects caused by the
      overexpression of LAT1 in cancer cells.

PMID- 30103562
TI  - Nuclear Magnetic Resonance Spectroscopy for In Situ Monitoring of Porous
      Materials Formation under Hydrothermal Conditions.
AB  - The employment of nuclear magnetic resonance (NMR) spectroscopy for studying
      crystalline porous materials formation is reviewed in the context of the
      development of in situ methodologies for the observation of the real synthesis
      medium, with the aim of unraveling the nucleation and growth processes mechanism.
      Both liquid and solid state NMR techniques are considered to probe the local
      environment at molecular level of the precursor species either soluble in the
      liquid phase or present in the reactive gel. Because the mass transport between
      the liquid and solid components of the heterogeneous system plays a key role in
      the synthesis course, the two methods provide unique insights and are
      complementary. Recent technological advances for hydrothermal conditions NMR are
      detailed and their applications to zeolite and related materials crystallization
      are illustrated. Achievements in the field are exemplified with some
      representative studies of relevance to zeolites, aluminophosphate zeotypes, and
      metal-organic frameworks.

PMID- 30103563
TI  - New 19-Residue Peptaibols from Trichoderma Clade Viride.
AB  - Trichoderma koningiopsis and T. gamsii belong to clade Viride of Trichoderma, the
      largest and most diverse group of this genus. They produce a wide range of
      bioactive secondary metabolites, including peptaibols with antibacterial,
      antifungal, and antiviral properties. The unusual amino acid residues of
      peptaibols, i.e., alpha-aminoisobutyric acid (Aib), isovaline (Iva), and the C
      terminal 1,2-amino alcohol make them unique among peptides. In this study, the
      peptaibiomes of T. koningiopsis and T. gamsii were investigated by HPLC-ESI-MS.
      The examined strains appeared to produce 19-residue peptaibols, most of which are
      unknown from literature, but their amino acid sequences are similar to those of
      trikoningins, tricholongins, trichostrigocins, trichorzianins, and trichorzins. A
      new group of peptaibols detected in T. koningiopsis are described here under the
      name "Koningiopsin". Trikoningin KA V, the closest peptaibol compound to the
      peptaibols produced by these two strains, was selected for structural
      investigation by short MD simulation, which revealed that many residues show high
      preference for left handed helix formation. The bioactivity of the peptaibol
      mixtures produced by T. koningiopsis and T. gamsii was tested on agar plates
      against bacteria, yeasts, and filamentous fungi. The results revealed
      characteristic differences in bioactivities towards the different groups of
      target microorganisms, which can be explained with the differences in their cell
      wall structures.

PMID- 30103564
TI  - Authenticity Testing and Detection of Eurycoma longifolia in Commercial Herbal
      Products Using Bar-High Resolution Melting Analysis.
AB  - The present study demonstrated High Resolution Melting (HRM) analysis combined
      with DNA barcode (Bar-HRM) as a fast and highly sensitive technique for detecting
      adulterants in Eurycoma longifolia commercial herbal products. Targeting the DNA
      barcoding of the chloroplastic region-ribulose biphosphate carboxylase large
      chain (rbcL) and the nuclear ribosomal region- internal transcribed spacer 2
      (ITS2), PCR amplification and HRM analysis using saturated Eva green dye as the
      source of fluorescence signals, was accomplished by employing a real-time cycler.
      The results were further validated by sequencing to identify unknown sequence
      from Genbank database and to generate phylogenetic tree using neighbour joint
      (NJ) analysis. Both of the DNA markers exhibited a distinguishable melting
      temperature and shape of the normalised curve between the reference and the
      adulterants. In the case of species identification, ITS2 was more successful in
      differentiating between species. Additionally, detection of admixture sample
      containing small traces of targeted E. longifolia DNA (w/v) can be detected as
      low as 5% for rbcL and less than 1% for ITS2, proving the sensitivity and
      versatility of the HRM analysis. In conclusion, the Bar-HRM analysis is a fast
      and reliable technique that can effectively detect adulterants in herbal
      products. Therefore, this will be beneficial for regulatory agencies in order to
      regulate food safety issues.

PMID- 30103565
TI  - Glycocalyx Preservation and NO Production in Fatty Livers-The Protective Role of
      High Molecular Polyethylene Glycol in Cold Ischemia Injury.
AB  - Improving the protection of marginal liver grafts during static cold storage is a
      major hurdle to increase the donor pool of organs. The endothelium glycocalyx
      quality of preservation influences future inflammatory and oxidative responses.
      One cellular pathway responsible for the formation of nitric oxide by endothelial
      cells is dependent on the stimulation of proteoglycans present in the glycocalyx.
      We investigated the impact of the glycocalyx preservation in static cold storage
      of fatty liver preserved in different preservation solutions on the endothelium
      mediated production of NO. Zucker fatty rat livers were preserved 24 h in static
      cold storage in either Institut Georges Lopez-1 (IGL-1) (n = 10), IGL-0 (i.e.,
      without PEG35) (n = 5) or Histidine-Tryptophan-Ketoglutarate (HTK) (n = 10)
      preservation solutions before being processed for analysis. For Sham group (n =
      5), the fatty livers were immediately analyzed after procurement. The level of
      transaminases and nitrites/nitrates were measured in the washing perfusate.
      Glycocalyx proteins expressions, Syndecan-1, glypican-1 and heparan sulfate (HS),
      were determined in the tissue (ELISA). Steatotic livers preserved 24 h in IGL-1
      preservation solution have a significant lower level of transaminases (aspartate
      aminotransferase (AST), alanine aminotransferase (ALT)) and less histological
      damages than steatotic livers preserved 24 h with HTK (p = 0.0152). The syndecan
      1 is significantly better preserved in IGL-1 group compared to HTK (p < 0.0001)
      and we observed the same tendency compared to IGL-0. No significant differences
      were observed with glypican-1. HS expression in HTK group was significantly
      higher compared to the three other groups. HS level in IGL-1 was even lower than
      IGL-0 (p = 0.0005) which was similar to Sham group. The better protection of the
      glycocalyx proteins in IGL-1 group was correlated with a higher production of NO
      than HTK (p = 0.0055) or IGL-0 (p = 0.0433). IGL-1 protective mechanisms through
      the formation of NO could be due to its better protective effects on the
      glycocalyx during SCS compared to other preservation solutions. This beneficial
      effect could involve the preservation state of syndecan-1 and the internalization
      of HS.

PMID- 30103568
TI  - The early embryonic development of the primitive moth, Neomicropteryx nipponensis
      lssiki (lepidoptera, micropterygidae).
AB  - This paper describes the early embryonic development of Neomicropteryx
      nipponensis from oviposition to the formation of the inner layer. Newly laid eggs
      are covered with many hygroscopic, gelatinous masses. The chorion is composed of
      a porous, spongy exochorion of variable thickness and of a thin endochorion. The
      eggs have a very thin periplasm and contain large amounts of yolk made of proteid
      and fatty yolk droplets. The processes of maturation division, fertilization, and
      cleavage are similar to those commonly found in lepidopteran eggs. The blastoderm
      of Neomicropteryx is very thin in comparison with that of other lepidopteran
      eggs. The small circular germ disk is formed on the ventral egg surface. It then
      invaginates deeply into the yolk to form a sac-shaped germ rudiment. The
      formation of the germ rudiment and of the embryonic membranes resembles that of
      swift moths, Endoclita (suborder Monotrysia) and of the caddisfly, Stenopsyche
      (Trichoptera), but differs from that of ditrysian Lepidoptera. As in other
      lepidopteran insects, the formation of the inner layer begins after completion of
      the germ band, which has a bilobed protocephalon and a slender protocorm. Unlike
      the situation in most lepidopteran eggs, yolk segmentation does not occur in N.
      nipponensis. During formation of the germ band, hydropyle cells are formed in the
      dorso-posterior region of the serosa; these are here reported for the first time
      in the eggs of holometabolan insects.

PMID- 30103567
TI  - How Would Economic Development Influence Carbon Productivity? A Case from Hubei
      in China.
AB  - Carbon productivity, defined as the gross domestic product (GDP) per unit of CO2
      emissions, has been used by provincial governments in China as in indicator for
      effort and effect in addressing climate-change problems. The aggregate impact of
      economic growth on carbon productivity is complex and worthy of extensive
      investigation to design effective environmental and economic policies. Based on a
      novel combination of the smooth transition regression model and the Markov regime
      switching regression model, this paper analyzes time series data on carbon
      productivity and economic growth from Hubei Province in China. The results show
      that the influence of economic growth on carbon productivity is highly nonlinear.
      In general, economic growth has a positive impact on improving carbon
      productivity. From a longitudinal perspective, this nonlinear positive impact is
      further divided into three stages, transiting from a high regime to a low regime
      and then back to a high regime. The high regime stage, in which economic growth
      has stronger positive influence on enhancing carbon productivity, is expected to
      last for considerably longer time than the low regime stage. It is more probable
      for a low regime stage to transit to a high regime. Once the relation of carbon
      productivity and economic growth enters the high regime status it becomes
      relatively stable there. If the government aims to achieve higher carbon
      productivity, it is helpful to encourage stronger economic development. However,
      simply enhancing carbon productivity is not enough for curbing carbon emissions,
      especially for fast growing economies.

PMID- 30103566
TI  - Effects of Quercetin on Proliferation and H2O2-Induced Apoptosis of Intestinal
      Porcine Enterocyte Cells.
AB  - Weanling stress and toxicosis, which are harmful to the health of pigs'
      intestines, are associated with oxidative stress. Quercetin (Que) is a
      polyphenolic compound that shows good anti-cancer, anti-inflammation and anti
      oxidation effects. This study aimed to elaborate whether or not Que promotes IPEC
      J2 (intestinal porcine enterocyte cells) proliferation and protects IPEC-J2 from
      oxidative damage. Thus, we examined the effects of Que on proliferation and H2O2
      induced apoptosis in IPEC-J2. The results showed that Que increased IPEC-J2
      viabililty, propelled cells from G1 phase into S phase and down-regulated gene
      levels of P27 and P21, respectively. Besides, H2O2-induced cell damage was
      alleviated by Que after different exposure times, and Que depressed apoptosis
      rate, reactive oxygen species (ROS) level and percentage of G1 phase cells and
      elevated the percentage of cells in G2 phase and S phase and mitochondrial
      membrane potential (Deltapsim) after IPEC-J2 exposure to H2O2. Meanwhile, Que
      reduced the value of Bax/Bcl-2 in H2O2 exposed cells. In low-degree oxidative
      damage cells, lipid peroxidation product malondialdehyde (MDA) content and
      superoxide dismutase (SOD) activity were increased. In turn, Que could reverse
      the change of MDA content and SOD activity in low-degree damage cells.
      Nevertheless, catalase (CAT) activity was not changed in IPEC-J2 incubated with
      Que under low-degree damage conditions. Interestingly, relative expressive levels
      of the proteins claudin-1 and occludin were not altered under low-degree damage
      conditions, but Que could improve claudin-1 and occludin levels, slightly. This
      research indicates that Que can be greatly beneficial for intestinal porcine
      enterocyte cell proliferation and it protects intestinal porcine enterocyte cells
      from oxidation-induced apoptosis, and could be used as a potential feed additive
      for porcine intestinal health against pathogenic factor-induced oxidative damages
      and apoptosis.

PMID- 30103569
TI  - The functional morphology of the musculature of squid (Loliginidae) arms and
      tentacles.
AB  - The arms and tentacles of squid (Family Loliginidae: Sepioteuthis sepioidea
      (Blainville), Loligo pealei (LeSueur), Loligo plei (Blainville), Loliguncula
      brevis (Blainville)) do not possess the hardened skeletal elements or fluid
      filled cavities that typically provide skeletal support in other animals.
      Instead, these appendages are made up almost entirely of muscle. It is suggested
      here that the musculature serves as both the effector of movement and as the
      skeletal support system itself. High-speed movie recordings were used to observe
      prey capture by loliginid squid. Extension of the tentacles (1 pair) during prey
      capture is probably brought about by contraction of transverse muscle fibers and
      circular muscle fibers. Contraction of longitudinal muscle fibers causes
      retraction of the tentacles. Torsion of the tentacles during extension may be the
      result of contraction of muscle fibers arranged in a helical array. The
      inextensible but manipulative arms (4 pairs) may utilize a transverse muscle mass
      to resist the longitudinal compression caused by contraction of the longitudinal
      muscles which bend the arms. A composite connective tissue/muscle helical fiber
      array may twist the arms.

PMID- 30103570
TI  - The organization of the octavolateralis area in actinopterygian fishes: A new
      interpretation.
AB  - The octavolateralis area of actinopterygian fishes can be subdivided into a
      dorsal lateralis area composed of first-order lateral line nuclei, and a ventral
      octavus area composed of nuclei receiving first-order input from the eighth
      nerve. Three patterns of organization of the lateralis area are recognized in the
      present study. The organization of this area in polypteriforms and chondrosteans
      is similar to that in chondrichthyans. On the basis of recent studies in
      chondrichthyans (McCready and Boord, '76; Boord and Campbell, '77; Bodznick and
      Northcutt, '80), it is hypothesized that this pattern reflects the subdivision of
      the lateral line system into mechanoreceptive and electroreceptive portions. As
      petromyzontid agnathans also share this pattern of organization, it is
      hypothesized that they are elecroreceptive. The lateralis area of holosteans and
      nonelectroreceptive teleosts exhibits a second organizational pattern that is
      hypothesized to reflect the loss of the electroreceptive portion of the lateral
      line system; it is suggested that electroreception was lost sometime between the
      chondrostean and teleostean radiations. Each group of electroreceptive teleosts
      is believed to have evolved electroreception independently (Bullock, '74), a
      situation that is reflected centrally by a third organizational pattern within
      the lateralis area, which is distinctly different from that of early radiations
      of electroreceptive fishes. The octavus area of actinopterygians exhibits two
      patterns of organization-that of polypteriforms, chondrosteans, and holosteans,
      and that of teleosts. The functional significance of these patterns has yet to be
      elucidated.

PMID- 30103571
TI  - The leukocytic organ of the megascolecid earthworm, Amynthas diffringens
      (annelida, oligochaeta).
AB  - Leukocytic organs of Amynthas diffringens are aggregations of leukocytes
      contained within a smooth muscle and stromal cell framework suspended in the
      coelom. Elongate processes of stromal cells subdivide each organ into numerous
      cell-filled compartments and are perforated by 130-nm pores that may permit the
      exchange of humoral substances between compartments, or between the organ and the
      surrounding coelomic fluid. We divide leukocytes within the organs into four
      morphotypes. Phagocytic leukocytes have many lysosomelike vesicles and may
      possess phagosomes. Mature types I, II, and III granulocytic leukocytes share
      certain features but are readily distinguished by cell shape and by the size,
      shape, and electron density of the cytoplasmic inclusions. Immature as well as
      mature phagocytes and granulocytes occur within these organs, suggesting that
      they are sites of leukocyte maturation and storage. Concentrations of leukocytes
      within the organs result in extensive cell to cell contact, especially within
      islets and tightly packed cords. Phagocytosis of cell debris occurs throughout
      the organs. Immature stages of the four morphotypes are difficult to distinguish
      even at high magnification, raising the possibility that they may originate from
      a common precursor. Our inability to observe mitoses or to detect lymphocytelike
      stem cells suggests that immature leukocytes migrate to the organs via coelomic
      fluid from as yet unidentified primary sites of production.

PMID- 30103572
TI  - The ovary of Fundulus heteroclitus.
AB  - Scanning and transmission electron microscopy, together with dissection and light
      microscopy, have produced heretofore unavailable structural detail of the ovary
      of Fundulus heteroclitus. Structural and functional interrelationships among
      developing follicles and other histological elements, particularly as they might
      relate to vascularization of follicles, oocyte development, and ovulation, are
      described and discussed. Mature eggs, ovulated into the ovarian lumen, accumulate
      in the posterior "ovisac" region of the ovary prior to oviposition. This "ovisac"
      region is thin-walled and apparently nongerminal. The temporary retention of
      ovulated eggs permits cyclical oviposition even though oogenesis and ovulation
      are asynchronous. The histological differences between the ovisac and the
      anterior ovigerous of the ovary are described. The lumenal epithelium of the
      ovisac displays a localized population of unusual cells with long cytoplasmic
      extensions. The ultrastructure of these cells suggests that they might function
      in the transport of ovulated eggs into the oviduct and/or in secreting the
      substance ("jelly") which forms the surface coat of extruded eggs.

PMID- 30103573
TI  - The structure of the chambered nautilus siphuncle: The siphuncular epithelium.
AB  - The siphuncle of the chambered nautilus (Nautilus macromphalus) is composed of a
      layer of columnar epithelial cells resting on a vascularized connective tissue
      base. The siphuncular epithelium taken from chambers that have not yet begun to
      be emptied of cameral liquid has a dense apical brush border. The great number of
      apical cell junctions (zonula adherens) compared to the number of nuclei suggests
      extensive interdigitation of these cells. The perinuclear cytoplasm of these
      preemptying cells is rich in rough endoplasmic reticulum. The siphuncular
      epithelium of both emptying and "old" siphuncle (which has already completed
      emptying its chamber) both show little rough endoplasmic reticulum but do contain
      extensive systems of mitochondria-lined infoldings of the basolateral plasma
      membranes. Active transport of NaCl into the extracellular space of this tubular
      system probably entrains the water transport involved in the chamber-emptying
      process. Both emptying and old siphuncular epithelium also show large basal
      infoldings (canaliculi) continuous with the hemocoel, which appear to be filled
      with hemocyanin. The apical cell junctions of emptying and old siphuncular
      epithelium contain septate desmosomes that may help to prevent back-flow of
      cameral liquid into the chambers.

PMID- 30103574
TI  - The ultrastructure of spermatogenesis in Labidocera aestiva (copepoda:
      Calanoida).
AB  - The fine structure of spermatogenesis is described for the marine calanoid
      copepod Labidocera aestiva. The mature spermatozoon is a slightly flattened, disc
      shaped cell without a flagellum or an acrosome. Primary spermatocytes in first
      meiotic prophase are characterized by large nuclei showing progressive
      condensation of chromatin. The cytoplasm contains free ribosomes, numerous
      mitochondria, cytoplasmic vesicles, centrioles, and perinuclear nuage. Densely
      staining cisternae are associated with the nuage of pachytene and diplotene
      primary spermatocytes. This association may represent the temporary
      differentiation of an acrosome. Synaptonemal polycomplexes are frequently present
      in the nuclei of zygotene, pachytene, and diplotene primary spermatocytes. Many
      of the intercellular bridges which join the germ cells throughout spermatogenesis
      appear occluded by systems of transverse membranous cisternae. After the second
      meiotic telophase, spermatids are incorporated into nongerminal accessory cells
      that may facilitate the release of spermatids from the testis and regulate the
      rate of spermatogenesis by phagocytosis. During spermiogenesis the mitochondria
      become closely applied to the nuclear envelope, the nuclear envelope fragments
      and forms an elaborate membrane complex, a pentalaminar plasma membrane develops,
      and electron-dense material accumulates on the inner and outer surfaces of the
      plasma membrane in the mature spermatozoon.

PMID- 30103575
TI  - Transformation of the intestinal epithelium of the larval anadromous sea lamprey
      Petromyzon marinus L. during metamorphosis.
AB  - The events in the transformation of the intestine of the larval lamprey into the
      adult intestine were followed through the seven (1-7) stages of metamorphosis in
      anadromous Petromyzon marinus L. Light and electron-microscope observations
      demonstrated that the processes of degeneration, differentiation, and
      proliferation are involved in the transformation. In the anterior intestine,
      degeneration of cells and the extrusion of others into the lumen results in the
      disappearance of secretory (zymogen) cells and the decline in numbers of
      endocrine and ciliated cells. Larval absorptive cells, with a prominent brush
      border, are believed to dedifferentiate into unspecialized columnar cells with
      few microvilli. Degeneration and removal of cells occurs by both autophagy and
      heterography and cells extruded into the lumen in the anterior intestine are
      phagocytosed by epithelial cells of the posterior intestine. The loss of
      epithelial cells during transformation results in the folding and degradation of
      parts of the basal lamina and in an extensive widening of the lateral
      intercellular spaces in all parts of the intestine. As metamorphosis is a
      nontrophic period of the lamprey life cycle, the possible morphological effects
      of starvation on the intestinal epithelium are discussed. The development of
      longitudinal folds is a consequence of the events of metamorphic transformation
      of the intestinal mucosa. Although an interaction between the epithelium and the
      underlying tissues is believed to be importent, the actual mechanism of fold
      development is unknown. The intestinal epithelium of adult lampreys develops from
      surviving cells of the larval (primary) epithelium. Unlike the situation in
      amphibians, there does not appear to be a group (nest) of undifferentiated larval
      cells which differentiate into the adult (secondary) epithelium. Instead, in
      lampreys, columnar cells that persist through the degradative processes seem to
      be the source of absorptive and ciliated cells and probably are responsible for
      mucous and secretory cells. Preliminary observations indicate that the intestinal
      epithelium of feeding adults is specialized into an anterior region which
      liberates a secretion, absorbs lipid, and possesses the machinery for ion
      transport. A posterior region absorbs lipid, secretes mucus, and likely is
      involved in some protein absorption.

PMID- 30103576
TI  - The structure of the head kidney in the mudskipper, Periophthalmus koelreuteri
      (pallas).
AB  - The head kidneys of adult Periophthalamus koelreuteri contain many functional
      glomerular nephorns which on the basis of this histochemical study, are
      indistinguishable from those of the typical opistonephros of marine teleosts. The
      anterior lobes resemble, in location and in the presence of intertubular
      erythropoeitic tissue, the pronephros in other species. The single nephron found
      there, however, does not differ significantly from the other nephrons of the head
      kidney. It is suggested, therefore, that the nephrons of the head kidney in this
      species are opisthonephric in origin.

PMID- 30103577
TI  - The sensory systems and feeding behavior of leafhoppers. I. The aster leafhopper,
      Macrosteles fascifrons stal (homoptera, cicadellidae).
AB  - The ultrastructure of the sensilla, and other structures, within the stylets and
      precibarium of Macrosteles fascifrons were examined by transmission and scanning
      electron microscopy. Precibarium is a new term, defined here, for the canal that
      precedes the cibarium inside the leafhopper head. Within the precibarium are
      found 20 chemosensilla and a previously undescribed structure, the precibarial
      valve. Twelve mechanosensilla, three in each stylet, are found within the
      maxillary and mandibular stylets. The relationship between all of these
      structures and feeding by the insect is detailed in a feeding mechanism
      hypothesis. It is concluded that leafhoppers (and probably all homopterans)
      utilize the precibarial chemosensilla alone for gustatory discrimination, the
      stylet sensilla for proprioception, and the precibarial valve for regulation of
      fluid uptake and compartmentalization of the sensilla.

PMID- 30103578
TI  - [Progress on minimally invasive treatment for calcaneal fracture].

PMID- 30103579
TI  - [Case-control study on self-setting calcium phosphate cement and allograft for
      Sanders II-IV fractures of calcaneus].
AB  - OBJECTIVE: To compare clinical results of Sanders II-IV fractures of calcaneus
      treated by self-setting calcium phosphate cement and allograft with locking
      reconstruction bone plate internal fixation. METHODS: From March 2012 to December
      2015, 48 patients with Sanders II-IV fractures of calcaneus were treated by open
      reduction and internal fixation through L-shape incision, bone grafting were
      performed on reserved bone defect of calcaneal fracture. The patients were
      divided into self-setting calcium phosphate cement and allograft group according
      to different materials. Twenty-eight patients in self-setting calcium phosphate
      cement group, including 23 males and 5 females aged from 22 to 52 years old with
      an average of (34.46+/-7.33) years old; 8 cases were type II, 11 cases were type
      III and 7 cases were type IV according to Sanders classification. Twenty patients
      in allograft group, including 17 males and 3 females aged from 24 to 55 years old
      with an average of(36.40+/-7.93) years old; 6 cases were type II, 7 cases were
      type III and 9 cases were type IV according to Sanders classification.
      Postoperative wound complications, Bohler angle before and after operation and 12
      months, Maryland functional score were evaluated. RESULTS: All patients obtained
      bone union, and were followed up from 12 to 42 months with an average of 25
      months. There were no statistical significance in Bohler angle and Manyland score
      before and after operation and 12 months between two groups. Five patients
      occurred wound complications in allograft group and 2 cases occurred wound
      complications in self-setting calcium phosphate cement and allograft group.
      CONCLUSIONS: Both of open reduction bone grafting and reconstructive plate
      internal fixation have good effective results for calcaneal fracture. Compared
      with allograft, self-setting calcium phosphate cement, which has no rejection
      response and less complications, has equal effects for calcaneal fracture and
      deserves to be popularized.

PMID- 30103580
TI  - [Improved anatomical locking plate internal fixation through tarsal sinus
      incision in treating Sanders III-IV calcaneal fractures].
AB  - OBJECTIVE: To investigate clinical effects of improved anatomical locking plate
      internal fixation through tarsal sinus incision in treating Sanders III and IV
      calcaneal fractures. METHODS: From February 2015 to October 2016, 35 patients
      with Sanders III and IV calcaneal fractures treated by improved anatomical
      locking plate internal fixation through tarsal sinus incision were collected,
      including 22 males and 13 females aged from 22 to 68 years old with an average of
      (42.3+/-12.7) years old. According to Sanders classification, 23 patients were
      type III and 12 patients were type IV. Postoperative complications were observed,
      Bo hler angle and Gissane angle before and after operation were compared, and
      Maryland foot function scoring standard was evaluated at 12 months after
      operation. RESULTS: All patients were followed up from 12 to 20 months with an
      average of (14.5+/-2.0) months, the length of incision ranged from 4.0 to 5.5 cm
      with an average of (4.7+/-0.4) cm. Superficial infection occurred in 1 patient,
      delayed union in 2 patients, gastrocnemius nerve injury in 1 patient. No
      complications such as steel plate exposure and fracture reduction loss occurred.
      Wound healing time ranged from 14 to 28 days with an average of(15.4+/-4.7) days,
      the fracture healing time ranged from 8 to 14 weeks with an average of (9.8+/
      1.9) weeks. Bo hler angle increased from preoperative (9.81+/-14.28) degrees  to
      3 days after operation (26.35+/-11.04) degrees , and (25.96+/-10.79) degrees  at
      12 months after operation(P<0.05). Gissane angle ranged from preoperative
      (122.54+/-16.79) degrees  to 3 days after operation (120.85+/-11.88) degrees ,
      and (120.62+/-11.44) degrees  at 12 months after operation and had statistical
      meaning. Maryland score increased from 12.66+/-4.10 before operation to 92.20 +/
      7.82 at 12 months after operation, and 32 patients got excellent results, 2 good
      and 1 moderate. CONCLUSIONS: Improved anatomical locking plate internal fixation
      through tarsal sinus incision in treating Sanders III and IV calcaneal fractures,
      which has advantages of less incision, less soft tissue injury, better fracture
      reduction and fixation, could receive good reduction and fixation. It is an
      effective method for Sanders III and IV fracture of calcaneus fracture.

PMID- 30103581
TI  - [Treatment of calcaneal fracture by closed reduction and minimally invasive plate
      fixation assisted with bidirectional distractor distraction].
AB  - OBJECTIVE: To investigate clinical effects of calcaneal fracture with closed
      reduction and minimally invasive plate fixation assisted with bidirectional
      distractor distraction. METHODS: From September 2015 to October 2016, 11 male
      patients(13 feet) with calcaneal fractures treated with bidirectional distractor
      distraction assisted with minimally invasive plate fixation were retrospectively
      studied. They were aged from 24 to 57 years old with an average of 36.4 years
      old;8 feet were type IIand 5 feet were type III according to Sanders
      classification. Postoperative incision, fracture healing, Bohler angle, Gissane
      angle were observed and Maryland scoring system was used to evaluate clinical
      effects. RESULTS: All fractures healed well without incision inflammation and
      incision disunion. All patients were followed up from 12 to 15 months with an
      average of 13.5 months. Bohler angle were improved from (9.6+/-7.3) degrees 
      before operation to (20.2+/-4.6)  degrees  at 1 year after operation, and had
      statistical meaning; Gissane angle increased from (92.7 +/-8.5) degrees  before
      operation to (121.7 +/-7.6)  degrees  at 1 year after operation. Maryland score
      at 1 year after operation was 88.79+/-8.25, and 11 feet got excellent results and
      2 feet moderate. CONCLUSIONS: Bidirectional distractor distraction assisted with
      minimally invasive plate fixation could effectively fix calcaneal fractures,
      reduce postoperative complications, and get satisfied results of postoperative
      images and functional recovery. It is one of effective methods for treating
      Sanders II and III calcaneal fractures.

PMID- 30103582
TI  - [Imaging measurement and clinical significance of occipitocervical angle in
      healthy people at different ages].
AB  - OBJECTIVE: To measure imaging data of occipitocervical angle in healthy people at
      different ages by X-ray. METHODS: One hundred and fifty asymptomatic
      volunteers(75 males and 75 females) aged from 20 and 70 years old with an average
      of(44.83+/-13.88) years old were divided into 5 groups according to different
      ages(20 to 29 years old, 30 to 39 years old, 40 to 49 years old, 50 to 59 years
      old and 60 to 70 years old), and 30 people in each group. All people underwent
      lateral radiography of neck on neutral position. McGregor line (the lowest
      connection line between upper margin of hard palate and occipital scales of
      plating), occipitocervical angle(OCA) formed by edge of C2 vertebral body,
      takami's occipitocervical angle formed between connection line of posterior
      marginal of C2 vertebral body and parallel lines of hard palate were collected.
      The data were performed statistical analysis according to gender and different
      ages, and analyzed correlation between OCA and TOCA. RESULTS: OCA of 75 males at
      different ages were (14.71+/-3.09) degrees  and(14.22+/-4.27) degrees  in 75
      females. TOCA of 75 males at different ages were (90.50+/-4.63) degrees  and
      (90.57+/-6.67)  degrees  in 75 females. There were no statistical difference in
      OCA and TOCA in people at different ages(P<0.05). There were no significant
      meaning among 5 groups at different ages in OCA and TOCA(P>0.05). The relation
      analysis results showed positive correlation between OCA and TOCA(r=0.454,
      P<0.01). CONCLUSIONS: The paper provided normal values for occipitocervical angle
      in population of southwestern China between 20 and 70 years old, and results may
      be useful for posterior occipitocervical fixation and fusion.

PMID- 30103583
TI  - [Tenotomy fixed on distal trochlea under arthroscopy for long head of biceps
      tendon and rotator cuff tear].
AB  - OBJECTIVE: To explore operative technique and clinical efficacy of tenotomy fixed
      on distal trochlea under arthroscopy for long head of biceps tendon and rotator
      cuff tear. METHODS: From June 2015 to November 2016, 23 patients with long head
      of biceps tendon and rotator cuff tear were treated with tenotomy fixed on distal
      trochlea under arthroscopy and rotator cuff repair. Among them, including 9 males
      and 14 females aged from 44 to 71 years old with an average of(56.38+/-5.74)
      years old, 3 patients on left shoulder injury, and the other 20 patients on right
      shoulder injury. Constant-Murley shoulder score, VAS score and improvement of
      shoulder ROM were assessed before operation, 3 months, 6 months and 12 months
      after operation. RESULTS: All patients were followed up from 12 to 18 months with
      an average of (15.37+/-4.82) months. Ipsilateral shoulder had no obvious pain,
      and ROM and muscle power almost returned to the level of patients' uninjured
      shoulder. Postoperative Constant-Murley score at 3 months was 67.47+/-12.19,
      74.82+/-13.26 at 6 months after operation and 93.47+/-10.19 at 12 months after
      operation, which were better than that of 39.62+/-12.39 before operation.
      According to Constant-Murley score, 18 patients got excellent results, 4 good and
      1 poor. There was statistical significance in VAS score before operation 6.85+/
      2.14 and 0.36+/-0.54 at 12 months after operation. Anteflexion of shoulder joint
      and abduction at 12 months after operation were (163.55+/-15.24) degrees ,
      (164.37+/-14.46) degrees , and improved more than before operation (75.52+/-6.31)
      degrees , (84.36+/-13.36) degrees . CONCLUSIONS: Clinical effects of tenotomy
      fixed on distal trochlea under arthroscopy for long head of biceps tendon and
      rotator cuff tear were satisfied, solving pains of shoulder joint, recovering
      shoulder joint functions without damaging appearance and muscle strength of
      musculus biceps brachii.

PMID- 30103584
TI  - [Clinical effects of percutaneous endoscopic transforaminal decompression for the
      treatment of lumbar spinal stenosis].
AB  - OBJECTIVE: To evaluate clinical effects of lumbar spinal stenosis by endoscopic
      transforaminal decompression, and to provide a theory basis for selection of
      surgical candidates. METHODS: From June 2014 to January 2016, clinical data of 87
      patients with lumbar spinal stenosis were retrospectively analyzed, including 45
      males and 42 females, aged from 25 to 81 years old with an average of 55.14 years
      old; 8 cases on L3,4, 61 cases on L4,5, 18 cases on L5S1. All patients underwent
      percutaneous edoscopic transforaminal decompression. Clinical symptoms and nerve
      functions were evaluated by VAS, ODI before operation, 3 and 6 months after
      operation, MacNab scoring was used to evaluate clinical effects. RESULTS:
      Postoperative incision of 87 patients healed well without complications, and
      obtained more than 6 months follow-up. VAS score before operation, 3 and 6 months
      after operation respectively were 63.88+/-8.56, 13.22+/-8.24, 6.83+/-9.43
      respectively;ODI score before operation, 3 and 6 months after operation were
      59.96+/-12.60, 9.08+/-10.55, 5.64+/-6.84 respectively. There was statistical
      significance in VAS and ODI score compared before operation and 3 and 6 months
      after operation. According to MacNab scoring, 41 cases obtained excellent
      results, 30 good, 7 moderate and 9 poor. CONCLUSIONS: Percutenous endoscopic
      transforaminal decompression for lumbar spinal stenosis could reach good clinical
      effects if choosing appropriate indications. For patients with yellow ligament
      hypertrophy or combined with some ossified stenosis, insufficient decompression
      may result in poor therapeutic effects.

PMID- 30103585
TI  - [Arthroscopic treatment of tibial intercondylar ridge avulsion fracture with
      double-root line double tunnel fixation technique].
AB  - OBJECTIVE: To discuss arthroscopic technique of double-root line double tunnel
      fixation for tibial intercondylar ridge avulsion fracture and its short-term
      followvup observational results. METHODS: From May 2012 to June 2017, 21 cases of
      tibial intercondylar ridge avulsion fractures were treated with arthroscope
      double line double tunnel. Among the patients, 16 males and 5 females were
      ranging in age from 17 to 45 years old, with an average of 29.6 years old, and
      injury to surgery time 3 to 6 days, with an average of 3.6 days. All the patients
      underwent arthroscopic exploration, fracture reduction, double root line
      fixation. The knee function was assessed at 3 and 6 months postoperatively using
      the Lysholm knee score, and the healing and resection of the patients were
      followed by X-ray examination. RESULTS: All patients were followed up for 7 to 23
      months, with an average of 12.8 months. All patients after fracture were bone
      healing, knee activity were gained their previous normal levels (ranged, 0
      degrees  to 130  degrees ), and no limb dysfunction. The average scores of
      Lysholm knee were(93.52+/-7.10) and(95.95+/-6.34) points in 3 months and 6 months
      after operation. CONCLUSIONS: Arthroscopic treatment of tibial intercondylar
      ridge avulsion fractures with double root line is simple and reliable, and can
      provide an ideal internal fixation method for tibial intercondylar ridge avulsion
      fractures.

PMID- 30103586
TI  - [Effect of serum of Bushen Huoxue prescription on rabbit with intervertebral disc
      motion segments in vitro culture].
AB  - OBJECTIVE: To compare effect of serum of Bushen Huoxue prescription on rabbit
      with intervertebral disc motion segments in vitro culture. METHODS: Twenty-four
      New Zealand white rabbits aged from 4 to 6 months and weighted from 2.5 to 3 kg
      were divided into medicated group and control group, 7 in each group. Rabbits
      were excuted under condition of asepsis, 28 spinal motion segments were taken out
      in each group, and segments were loaded in spinal motion segments in vitro and
      cultured in culture apparatus. Nutrient solution of medicated group contain 10%
      serum of Bushen Huoxue prescription, and 10% blank serum in control group. Seven
      discs between two groups were taken out and observed by histomorphology,
      proteoglycan PAS/AB stining, collagen II immunohistochemical staining, AGG,
      Col2aI by PCR test before culture and on the 3th, 7th and 14th day after culture.
      RESULTS: Histomorphology results showed the formation of medicated group was
      better than that of control group at 1 week after culture. PAB/AB test results
      showed content of poteoglycan between two groups were decreased.
      Imunohistochemical results showed content of collagen II in medicated group were
      obviously increased than that of control group at 3 days, but decreased obviously
      at 1 week than that of control group. PCR results showed expression of Agg in
      medicated group was obviously decreased than that of control group, but no
      statistical significance between two groups on the 7 th and 14 th day. Expression
      of Col2aI between two groups at 3 days were increased, and medicated group
      increased obviously more, while there were no significant difference between two
      groups. CONCLUSIONS: Serum of Bushen Huoxue prescription could delay
      intervertebral disc degeneration at short time for it is relate with improving
      circulation, inhibiting inflammatory, regulating extracellular matrix, so the
      prescription plays an important role in early prevention and treatment for
      intervertebral disc degeneration.

PMID- 30103587
TI  - [Resveratrol and puerarin on peak bone mass in young rats].
AB  - OBJECTIVE: To compare effects of resveratrol, puerarin and the compounds on peak
      bone mass in rats. METHODS: Forty SPF Wistar rats weighed 109.45 g to 119.44 g
      with an average of 115.87 g were selected. After 3 days' adaption, rats were
      divided into control group (the same volume of distilled water per day), puerarin
      group(15.4 mg/kg puerarin daily), resveratrol group (8.4 mg/kg resveratrol
      daily), compound drug group (daily dose of 8.4 resveratrol added 15.4 mg/kg of
      puerarin) and 10 in each group. The body weight of the rats was monitored at
      every 7 days and body bone density was measured at every month. All rats were
      sacrificed after 3 months. The bone mineral density of femur and vertebrae was
      detected by dual energy X-ray absorptiometry; bone biomechanics, VG staining was
      used to analyze bone histomorphometry;ELISA was used to detect serum bone
      metabolic index and microstructure of femur were scanned with Micro-CT scanner.
      RESULTS: There were no significant differences in body weight among groups during
      exoeriment. Bone mineral density results showed BMD of femur and vertebrae in the
      other three groups were significantly increased, and R+P group was significantly
      higher than PR group and RES group(P<0.05) by compared with CON group;three-point
      bending and compression test results showed compared with CON group, other three
      groups of femoral and vertebral maximum load values were significantly increased,
      and P+R group was higher than PR group and RES group, but elastic modulus was not
      statistically significant. Bone histomorphometry showed that number of trabecular
      bone in other three groups were significantly increased compared with CON group,
      separation of trabecular bone were significantly reduced, continuity was
      improved, and R+P group was significantly better than RES and PR group. The
      results of Micro-CT scan showed that separation of trabecular bone were
      significantly reduced, continuity were improved in other three groups, and R+P
      group was significantly better than RES and PR group. The numbers of trabecular
      bone (Tb.N), trabecular bone thickness (Tb.Th), volume of trabecular bone (BV/TV)
      in PR group, RES group and R+P group were significantly higher than CON group,
      but trabecular bone separation (Tb.Sp) was significantly reduced. Serum levels
      results showed, level of OC in the other three groups were higher than control
      group(P<0.05), content of TRACP 5b decreased, and level of OC in P+R group was
      significantly higher than PR group and RES group, content of TRACP 5b was no
      significant change. CONCLUSIONS: Compound of puerarin and resveratrol assigned in
      a 1:1 ratio could improve bone mineral density and bone mass in young rats,
      enhance biomechanical properties of bone, promote mineralization and maturation
      of osteoblasts, inhibit osteoblastic bone resorption, and is better than the role
      of their respective monomers. The paper showed that traditional Chinese medicine
      compound medicine will be used as a new way to prevent and treat osteoporosis.

PMID- 30103588
TI  - [Comparison of clinical efficacy of complete and incomplete radical debridement
      for spinal tuberculosis: a Meta-analysis].
AB  - OBJECTIVE: To compare clinical efficacy of complete and incomplete radical
      debridement for spinal tuberculosis by Meta-analysis. METHODS: The literatures of
      RCT or non-RCT with complete and incomplete radical debridement for spinal
      tuberculosis from Medline, EMBASE, Cochrane Library, Web of Science, CBM, CNKI
      and Wanfang were searched from the time of creating database to July, 2017. Two
      independent reviewers identified eligible studies, extracted data and evaluated
      risk of bias of included studies. Meta analysis were performed by Revman 5.3 and
      GRADE system were used to grade evidence. Recurrence rate, adverse effects,
      healing time, chemotherapy duration, spinal deformity by correction angle, bone
      fusion time in interface of intervertebral, erythrocyte sedimentation rate and C
      reaction protein were compared between two groups. RESULTS: Totally 9 literatures
      were chosen, including 5 RCT and 4 non-RCT with 1 302 patients. Compared with
      incomplete radical debridement, complete radical debridement had lower recurrence
      rate [OR=0.14, 95%CI(0.08, 0.22), P<0.000 01], lower rate of adverse
      effects[OR=0.18, 95%CI(0.12, 0.27), P<0.000 01], shorter healing time[MD=-4.80,
      95%CI(-5.14, -4.45), P<0.000 01]and chemotherapy duration [MD=-5.25, 95%CI(-5.64,
      -4.86), P<0.000 01], larger spinal deformity by correction angle[MD=4.88,
      95%CI(3.55, 6.27), P<0.000 01], smaller erythrocyte sedimentation rate[MD=-8.74,
      95%CI(-11.99, -5.49), P<0.000 01] and C-reaction protein [MD=-4.75, 95%CI(-8.61, 
      0.88), P=0.02] . However, there was no difference on bone fusion time in
      interface of intervertebral between two groups[MD=-0.19, 95%CI(-0.50, 0.12),
      P=0.23]. CONCLUSIONS: Compared with incomplete radical debridement, complete
      radical debridement has advantages of lower incidence of recurrence, lower rate
      of adverse reaction, shorten healing time and chemotherapy time, recovered
      faster. Techniques are selected according to indication of patients individual,
      complete radical debridement is recommended at the same indications.

PMID- 30103589
TI  - [Open reduction and bone graft with internal fixation through bone window for the
      treatment of type B4 distal radius fractures].
AB  - OBJECTIVE: To explore clinical effect of open reduction and bone graft with
      internal fixation through bone window for the treatment of type B4 distal radius
      fractures. METHODS: From January 2015 to June 2016, 13 patients with type B4
      distal radius fractures treated with bone graft with internal fixation through
      bone window, including 9 males and 4 females aged from 18 to 36 years old with an
      average of 26.3 years old. Fractures were classified to type B4 according to
      AO/OTA classification. Fracture healing and postoperative complication were
      observed, VAS score was used to evaluate pain, and Cooney wrist scoring was
      applied to evaluate recovery of function. RESULTS: All patients were followed up
      from 10 to 14 months with an average of 12.4 months. Fracture healed from 4 to
      6months with an average of 5.2 months. According to Cooney wrist scoring, 10 got
      excellent results, 2 good and 1 moderate. VAS score was 1.0+/-1.1, grip strength
      of contralateral ratio was (88.2+/-2.7)%, palmer tilt angle was (12.2+/-3.8)
      degrees , ulnar drift angle was (19.3+/-5.4) degrees , wrist flexion mobility was
      (118.1+/-2.3) degrees , forearm rotation motion was (158.0+/-13.0) degrees . No
      osteoarthritis occurred and symptoms occurred during follow-up. CONCLUSIONS: Open
      reduction and bone graft with internal fixation through bone window for the
      treatment of type B4 distal radius fractures, which has advantages of satisfied
      clinical effects, less complications, is one of the effective method for type B4
      distal radius fractures.

PMID- 30103590
TI  - [Clinical outcomes of buttress plating in treating posterior Pilon fractures
      through modified posteromedial approach].
AB  - OBJECTIVE: To explore clinical outcomes of buttress plating in treating posterior
      Pilon fracture by amodified posteromedial approach. METHODS: From July 2014 to
      January 2015, 10 patients with posterior Pilon fracture were respectively
      analyzed, including 7 females and 3 males, aged from 31 to 54 years old. One
      patient were type , 3 patients were type IIand 6 patients were type III according
      to classification of Pilon fracture by YU Guang-rong. All patients were treated
      by buttress plating through amodified posteromedial approach. Postoperative
      complications, fracture healing and reduction were observed, AOFAS score were
      used to evaluate function recovery at 1 year after operation. RESULTS: All
      patients were followed up for 12 to 18 months with an average of(14.1+/-3.2)
      months. All incisions were primarily healed at stage I without wound
      complication, neurovascular injuries or musculus flexor contracture. According to
      Burwell-Charnley imaging scoring, 8 patients got anatomical reduction and 2
      patients got moderate reduction. All fracture got healing from 12 to 16 weeks
      with an average of(13.2+/-1.8) weeks. According to AOFAS score at 1 year after
      operation, 8 got excellent results and 2 moderate. All patients returned to work
      at about(4.7+/-1.4) months (ranged from 3 to 6 months) after operation.
      CONCLUSIONS: Buttress plating using a modified posteromedial approach in treating
      posterior Pilon fractures is an effective method, has less complications, and
      could recovery early weight-bearing functional exercise.

PMID- 30103591
TI  - [Descending branch of anterior lateral malleolar artery based anterograde island
      flaps for reconstruction of foot and ankle defects].
AB  - OBJECTIVE: To explore surgical method and clinical effects of descending branch
      of the anterior lateral malleolar artery based anterograde island flap for
      repairing foot and ankle wounds. METHODS: Nine patients with skin defects of foot
      and ankle repaired by descending branch of the anterior lateral malleolar artery
      based anterograde island flap were studied from June 2015 to January 2017,
      including 6 males and 3 females aged from 32 to 63 years old. The wound were
      located on foot and ankle and associated with exposure of bone, tendon, blood
      vessels or nerves. The surface of wound located on foot in 6 patients, and 3
      patients in ankle joint. The area of defect ranged from 1.5 cm*2.0 cm to 6.0
      cm*13.0 cm, and the area of flap ranged from 2.0 cm*3.0 cm to 7.0 cm*15.0 cm. The
      donor site was skin grafted with split-thickness skin from abdomen. Appearance,
      texture, condition of donor site of island flaps after operation were observed,
      satisfied degree of clinical effects were evaluated by ZHANG Hao's evaluation,
      and AOFAS score were used to evaluate function. RESULTS: Circulations of flaps in
      9 cases were stable without blockage, and healed well at 2 weeks after operation.
      All patients were followed up from 2 to 18 months with an average of(8.0+/-2.3)
      months. All flap were survived at stage I, pedicles looked smooth and tidy, no
      cat-ear formed, the texture of flap was soft with satisfied appearance, the color
      was near to surrounding skin. The surface of wound were tidy after skin graft of
      donor sites without scar hypertrophy. Nine patients got satisfied results
      according to ZHANG Hao's evaluation, and AOFAS score was excellent. CONCLUSIONS:
      Descending branch of the anterior lateral malleolar artery based anterograde
      island flap for repairing foot and ankle wounds, which has advantages of protect
      main vessel, thin flap, is a simple and effective method.

PMID- 30103592
TI  - [Vacuum sealing drainage with anterolateral thigh perforator flap for repair foot
      soft tissue defect].
AB  - OBJECTIVE: To investigate clinical effect of vacuum sealing drainage(VSD) with
      anterolateral thigh perforator flap for repair foot soft tissue defect. METHODS:
      From September 2014 to September 2016, 45 patients with foot soft tissue defect
      repaired by VSD with anterolateral thigh perforator flap, including 31 males and
      14 females aged from 17 to 55 years with an average of 36 years old. Thirty
      patients were dorsal soft tissue defects, and 15 patients were plantar soft
      tissue defects. Sizes of soft tissue defect ranged from 7 cm*10 cm to 11 cm*18
      cm, the wound was contaminated seriously and assisted with deep soft tissue
      exposure. Emergency surgical wound debridement with VSD treatment were performed,
      and wound surface was cleaned after 5 to 7 days, free anterolateral thigh flap
      were repaired. Sizes of flap ranged from 9 cm*12 cm to 13 cm*21 cm. Appropriate
      method was used to repair flap donor area. RESULTS: All 45 free propeller flap
      were survived without skin edge necrosis, ulcerative infection. Forty patients
      were followed up from 3 to 24 months with an average of 13 months. Flap showed
      good color, beautiful appearance, good elasticity, soft texture, but without
      obvious bloated, the wood of leg healed well. CONCLUSIONS: VSD with anterolateral
      thigh perforator flap for repair foot soft tissue defect could effective control
      wound soft tissue infection, receive reliable flap blood supply and skin flap
      could repaired at stage I. It is an effective method for repairing foot soft
      tissue defects.

PMID- 30103593
TI  - [Iliac langerhans cell histiocytosis: a case report].

PMID- 30103594
TI  - [Application of total en bloc spondylectomy in spinal tumors].
AB  - Total en bloc spondylectomy is a surgical technique cutting off tumors of spine
      and its satellite. Previous studies have shown that this technique could reduce
      postoperative recurrence rate of spinal tumor, but surgical indications are not
      unified. Wide application of spinal tumor surgical staging and life expectancy
      system make it more clear for surgery. However, it is difficult to carry out
      extensive operation for the characteristics of more bleeding, great difficulty
      and high risk. As for continuous improvement of TES technology, application of
      endoscopy and appearance of 3D printing artificial vertebral body could push the
      operation becoming mature.

PMID- 30103595
TI  - [Advanced progress on the treatment of anterior approach to the thoracolumbar
      vertebral fractures].
AB  - Thoracolumbar fractures are common and severe traumas. Anterior approaches can
      achieve adirect spinal cord decompression and reconstruct anterior column height
      what load bearing the major load distribution of the spine. Therefore, anterior
      approach is an important method in the treatment of thoracolumbar fractures. With
      the application of pedicle screw, most of the patients were treated with
      posterior approaches.Because of the unique advantages of anterior approach, the
      posterior approach can not be replaced it.The review summarizes the biomechanical
      characteristics? indications? fixation devices? bone grafting method and
      technique of the anterior approach and in order to provide better evidence for
      clinical treatment of thoracolumbar fractures.

PMID- 30103596
TI  - [Progress on treatment for patellofemoral arthritis].
AB  - As a common disease of knee joint disease, the diagnosis and treatment of
      patellofemoral arthritis has not clear clinical consensus at present,
      conservative treatment only has a certain value for the disease with early stage
      and single disease. With the continuous improvement of understanding of
      pathogenesis and advancement of surgical techniques, minimally invasive and joint
      replacement technology has been rapid development, more and more alternative
      treatment options could be chosen. Technique of osteotomy of tibial tuberosity
      and removal of patella at the early stage were seldom used. According to
      development stage of disease, and combined with age, economic capacity, patients
      considering knee joint functional requirements and other factors, the balance of
      soft tissue under arthroscopy and denervation for cartilage injury in elderly
      patients with grade I to III surgery is more appropriate, and joint replacement
      is effective for cartilage injury in elderly patients with grade IV. Early debate
      is focus on total knee arthroplasty whether exist excessive medical treatment,
      patellofemoral joint replacement meet to demand for replacement of single
      patellofemoral degeneration with improvement of prosthesis design. Due to
      technical difficulties of cartilage transplantation and anatomical
      characteristics of patellofemoral joint, report of application of cartilage
      transplantation for patellofemoral arthritis is less, but with continuous
      improvement of technology, cartilage transplantation will be a good method for
      improving clinical symptoms, reducing medical costs, putting off joint
      replacement time.

PMID- 30103597
TI  - Additional lesions seen in magnetic resonance imaging of breast cancer patients:
      the role of second-look ultrasound and imaging-guided interventions.
AB  - Purpose: The purpose of this study was to investigate the final outcomes of
      magnetic resonance imaging (MRI)-identified additional lesions (MRALs) in breast
      cancer patients and the role of second-look ultrasound (SLUS) and imaging-guided
      interventions. Methods: We analyzed breast cancer patients with MRALs on
      preoperative MRI between January and June 2012. MRALs were defined as additional
      lesions suspected on MRI but not suspected on mammograms or ultrasound. The
      malignancy rate of MRALs, MRI-based Breast Imaging Reporting and Database System
      (BI-RADS) category, positional relationship with the index cancer, MRI-concordant
      lesion visibility on SLUS, performance of imaging-guided interventions, and total
      mastectomy (TM) rates were evaluated for the confirmed lesions. Results: Among
      the 119 confirmed lesions, SLUS and imaging-guided interventions were performed
      in 94 (79.0%) and 82 cases (68.9%), respectively. The malignancy rate was 68.1%
      (81 of 119), and was significantly higher in BI-RADS 4C-5 lesions than in 4A-4B
      lesions (94.6% vs. 56.1%, P<0.01) and in ipsilateral same-quadrant lesions than
      in contralateral lesions (84.2% vs 33.3%, P<0.01). The lesion visibility rate on
      SLUS was 90.4%. The malignancy rate was not significantly different according to
      lesion visibility on SLUS. The TM rate in the 98 cases with ipsilateral MRALs was
      37.8%, while it was significantly lower in patients who underwent an imaging
      guided intervention than in those who did not (27.9% vs. 54.1%, P=0.017).
      Conclusion: MRALs show a high probability of malignancy, especially if they are
      ipsilateral. SLUS and imaging-guided interventions can eliminate many unnecessary
      TMs.

PMID- 30103598
TI  - Benchmark Electronic Structure Calculations for H3O+(H2O) n, n = 0-5, Clusters
      and Tests of an Existing 1,2,3-Body Potential Energy Surface with a New 4-Body
      Correction.
AB  - We report extensive benchmark CCSD(T) Complete Basis Set (CBS) estimates of the
      binding energies, structures, and harmonic frequencies of H3O+(H2O) n clusters, n
      = 0-5, including all currently known low-lying energy isomers. These are used to
      test a previously reported many-body (up to 3-body interactions) CCSD(T)-based
      potential energy surface (PES) for the hydrated proton. A new 4-body term for the
      hydronium-water-water-water interactions is introduced. This term is aimed at
      refining the relative energies of isomers of the H3O+(H2O) n, n = 4, 5 clusters.
      The test results of the revised PES against the benchmark demonstrate the high
      accuracy of the revised PES.

PMID- 30103599
TI  - Machine-Learning-Guided Mutagenesis for Directed Evolution of Fluorescent
      Proteins.
AB  - Molecular evolution based on mutagenesis is widely used in protein engineering.
      However, optimal proteins are often difficult to obtain due to a large sequence
      space. Here, we propose a novel approach that combines molecular evolution with
      machine learning. In this approach, we conduct two rounds of mutagenesis where an
      initial library of protein variants is used to train a machine-learning model to
      guide mutagenesis for the second-round library. This enables us to prepare a
      small library suited for screening experiments with high enrichment of functional
      proteins. We demonstrated a proof-of-concept of our approach by altering the
      reference green fluorescent protein (GFP) so that its fluorescence is changed
      into yellow. We successfully obtained a number of proteins showing yellow
      fluorescence, 12 of which had longer wavelengths than the reference yellow
      fluorescent protein (YFP). These results show the potential of our approach as a
      powerful method for directed evolution of fluorescent proteins.

PMID- 30103600
TI  - Combinatory Biosynthesis of Prenylated 4-Hydroxybenzoate Derivatives by
      Overexpression of the Substrate-Promiscuous Prenyltransferase XimB in Engineered
      E. coli.
AB  - Prenylated aromatic compounds are important intermediates in the biosynthesis of
      bioactive molecules such as 3-chromanols from plants, ubiquinones from
      prokaryotes and meroterpenoids from sponges. Biosynthesis of prenylated aromatic
      compounds using prokaryotic microorganisms has attracted increasing attention in
      the field of synthetic biology. In this study, we demonstrated that the
      production of 3-geranyl-4-hydroxybenzoic acid (GBA) and a variety of GBA
      analogues was feasible in a metabolically engineered E. coli by using XimB, a
      special prenyltransferase involved in the biosynthesis of xiamenmycin A in
      Streptomyces xiamenensis 318. XimB exhibits broad substrate specificity and can
      catalyze the transfer reaction of prenyl moieties with different carbon chain
      lengths to both the natural substrate 4-hydroxybenzoate (4-HBA) and to different
      substituted 4-HBA derivatives at C-2 and C-3. Feeding 4-HBA to an engineered E.
      coli equipped with a hybrid mevalonate pathway increased the production of GBA up
      to 94.30 mg/L. Considerable amounts of other GBA derivatives, compounds 4, 5, 6,
      7, and 9, can be achieved by feeding precursors. The plug-and-play design for
      inserting C5, C15, and C20 prenyl diphosphate synthetases under the control of
      the T7 promoter resulted in targeted production of 3-dimethylallyl, 3-farnesyl-,
      and 3-geranylgeranyl-4-hydroxybenzoic acid, respectively. Furthermore, the
      valuable benzopyran xiamenmycin B was successfully produced in E. coli R7-MVA by
      coexpression of a complete biosynthetic gene cluster, which contains ximBDE.

PMID- 30103601
TI  - In Situ Measurement of the Plane-Strain Modulus of the Solid Electrolyte
      Interphase on Lithium-Metal Anodes in Ionic Liquid Electrolytes.
AB  - We present an experimental approach for in situ measurement of elastic modulus of
      the solid electrolyte interphase (SEI), which is formed from reactions between a
      lithium thin-film [on a polydimethylsiloxane (PDMS) substrate] and a room
      temperature ionic liquid (RTIL) electrolyte. The SEI forms under a state of
      compressive stress, which causes buckling of the sample surface. In situ atomic
      force microscopy is used to measure the dominant wavelength of the wrinkled
      surface topography. A mechanics analysis of strain-induced elastic buckling
      instability of a stiff thin film on a soft substrate is used to determine the
      plane strain modulus of the SEI from the measured wavelength. The measurements
      are performed for three RTIL electrolytes: 1-butyl 1-methylpiperidinium
      bis(trifluoromethylsulfonyl)imide (P14 TFSI) without any lithium salt, 1.0 M
      lithium bis(trifluoromethylsulfonyl)imide (Li TFSI) in P14 TFSI, and 1.0 M
      lithium bis(fluorosulfonyl)imide (Li FSI) in P14 TFSI to investigate the
      influence of lithium salts on the plane strain modulus of the SEI. The
      measurements yield plane-strain moduli of approximately 1.3 GPa for no-salt P14
      TFSI and approximately 1.6 GPa for 1.0 M Li TFSI in P14 TFSI and 1.0 M Li FSI in
      P14 TFSI. The experimental technique presented here eliminates some of the
      uncertainties associated with traditional SEI mechanical characterization
      approaches and offers a platform to engineer an SEI with desired mechanical
      properties by approaches that include altering the electrolyte composition.

PMID- 30103602
TI  - Thermally Stimulated Light Reflection and Photoluminescence of BaTiO3.
AB  - Perovskites have been attracting attention because of their considerable
      luminescence properties. A conventional perovskite such as BaTiO3 has no
      intrinsic photoluminescence. Doping with rare metals, nanocrystallization, and
      addition of organometallic halides induce significant photoluminescence and
      photovoltages. Here, we report anomalous light reflection and photoluminescence
      of BaTiO3 on heating. Light absorption shifted from the near-ultraviolet region
      to the visible region on heating. The small emission peaks at around 400-500 nm
      disappeared and new peaks appeared above 800 nm; the quantum yields of these
      peaks were less than 1% and more than 7%, respectively.

PMID- 30103603
TI  - Dynamic Protein Adsorption onto Dendritic Polyglycerol Sulfate Self-Assembled
      Monolayers.
AB  - Biomaterial surfaces that are in contact with blood are often prone to unspecific
      protein adsorption and the activation of the blood clotting cascade. Hence, such
      materials usually must be functionalized with low-fouling or anticoagulant
      polymer coatings to increase their performance and durability with respect to
      various applications, for example as implants or in biomedical devices. Many
      coatings are based on anionic polymers, such as heparin, and are known to have
      pronounced anticoagulant effects. To assess the ability of a surface to prevent
      biofouling and to get further insight into its underlying mechanism, studies of
      the protein adsorption on self-assembled monolayers (SAMs) are often used as a
      predictive tool. In this article, we synthesized thioctic acid-functionalized
      dendritic polyglycerol sulfate (dPGS), which is a well-known synthetic heparin
      mimetic, and immobilized it onto gold model surfaces. The anionic dPGS SAMs were
      characterized via contact angle measurements and ellipsometry and compared to
      their neutral dendritic polyglycerol (dPG) counterparts with respect to their
      single protein adsorption of the two most abundant blood proteins albumin (Alb)
      and fibrinogen (Fib). In addition, we used QCM-D and ToF-SIMS as complementary
      techniques to investigate the dynamic, mixed, and sequential adsorption of Alb
      and Fib. Our results clearly demonstrate an incomplete Vroman effect and indicate
      the rearrangement of the adsorbed protein layers, which is presumably drive by
      ionic interactions between the two proteins and the anionic dPGS surface.

PMID- 30103604
TI  - Blinking Suppression in Highly Excited CdSe/ZnS Quantum Dots by Electron Transfer
      under Large Positive Gibbs (Free) Energy Change.
AB  - Semiconductor quantum dots with stable photoluminescence are necessary for next
      generation optoelectronic and photovoltaic devices. Photoluminescence intensity
      fluctuations of cadmium and lead chalcogenide quantum dots have been extensively
      investigated since the first observation of blinking in CdSe nanocrystals in
      1996. In a quantum dot, blinking originates from stochastic photocharging,
      nonradiative Auger recombination, and delayed neutralization. So far, blinking is
      suppressed by defect passivation, electron transfer, and shell preparation, but
      without any deep insight into free energy change of electron transfer. We report
      real-time detection of significant blinking suppression for CdSe/ZnS quantum dots
      exposed to N, N-dimethylaniline, which is accompanied by a considerable increase
      in the time-averaged photoluminescence intensity of quantum dots. Although the
      Gibbs (free) energy change (Delta Get = +2.24 eV), which is estimated
      electrochemically and from density functional theory calculations, is unfavorable
      for electron transfer from N, N-dimethylaniline to a quantum dot in the minimally
      excited (band-edge) state, electron transfer is obvious when a quantum dot is
      highly excited. Nonetheless, Delta Get crosses from the positive to negative
      scale as the solvent dielectric constant exceeds 5, favoring electron transfer
      from N, N-dimethylaniline to a quantum dot excited to the band-edge state. Based
      on single-molecule photoluminescence and ensemble electron transfer studies, we
      assign blinking suppression to the transfer of an electron from N, N
      dimethylaniline to the hot hole state of a quantum dot. In addition to blinking
      suppression by electron transfer, complete removal of blinking is limited by
      short-living OFF states induced by the negative trion.

PMID- 30103605
TI  - Disordered Nanoparticle Packings under Local Stress Exhibit Avalanche-Like,
      Environmentally Dependent Plastic Deformation.
AB  - Nanoindentation experiments on disordered nanoparticle packings performed both in
      an atomic force microscope and in situ in a transmission electron microscope are
      used to investigate the mechanics of plastic deformation. Under an applied load,
      these highly porous films exhibit load drops, the magnitudes of which are
      consistent with an exponential population distribution. These load drops are
      attributed to local rearrangements of a small number of particles, which bear
      similarities to shear transformation zones and to the T1 process, both of which
      have been previously predicted for disordered packings. An increase in the
      relative humidity results in an increase in the number of observed load drops,
      indicating that the strength of the particle interactions has a significant
      effect on the modes of plastic deformation. These results suggest how disordered
      nanoparticle packings may be expected to behave in devices operating under
      varying environments.

PMID- 30103606
TI  - Reversible Photo- and Thermoresponsive, Self-Assembling Azobenzene Containing
      Zwitterionic Polymers.
AB  - Commercially available azo dyes bearing amino groups were grafted to zwitterionic
      copolymers composed of cyclic anhydride functionality. The zwitterionic
      copolymers were prepared for the first time by polymerizing sulfobetaine (SB)
      monomer with maleic anhydride (MA) under conventional free radical polymerization
      as well as reversible addition-fragmentation chain transfer (RAFT)
      polymerization. Poly(SB- co-MA) self-assembled in deionized water. Azobenzene
      grafted zwitterionic poly((SB- co-MA)- g-Azo) exhibited multiresponsive behavior.
      As confirmed by UV-vis spectroscopy, trans -> cis isomerization of the azo group
      was responsible for the photo- and thermal responsive behavior. The
      photoisomerization was reversible, and no photoaging was detected during the
      repeated exposure to UV and visible light. The water-soluble nature of
      photoresponsive azo dye grafted copolymers makes it suitable for applications in
      biological systems.

PMID- 30103607
TI  - Synthesis and Characterization of Quaternized Poly(beta-amino ester) for Highly
      Efficient Delivery of Small Interfering RNA.
AB  - The development of non-viral vectors for gene delivery has gained attention over
      the past decades. Specifically, poly(beta-amino ester) (PBAE) has shown great
      potential for improving the delivery of gene therapeutics. It has been observed
      that low-molecular-weight PBAE displayed low transfection activities, while
      quaternization could enhance the transgene expression efficacy of PBAE. Herein,
      PBAE quaternary ammonium salt (PBAEQAS) was synthesized to increase the positive
      charge of the polymers, which resulted in an increase in siRNA binding efficiency
      based on self-assembly electrostatic interaction. Specifically, the nanoparticle
      surface was positively charged, which increased the uptake ability of siRNA.
      Compared with acrylate-PBAEQAS/siNC nanoparticles and amine-PBAEQAS/siNC
      nanoparticles, acrylate-PBAEQAS/siSurvivin nanoparticles and amine
      PBAEQAS/siSurvivin nanoparticles induced more-efficient cell apoptosis and gene
      silencing. All these results suggest that PBAEQAS would be a promising gene
      delivery vector for cancer treatment.

PMID- 30103608
TI  - High-Throughput Phosphorylation Screening and Validation through Ti(IV)
      Nanopolymer Functionalized Reverse Phase Phosphoprotein Array.
AB  - Protein phosphorylation is one of the most important and widespread molecular
      regulatory mechanisms that controls almost all aspects of cellular functions in
      animals and plants. Here, we introduce a novel chemically functionalized reverse
      phase phosphoprotein array (RP3A) to capture and measure phosphoproteomes. RP3A
      uses polyamidoamine (PAMAM) dendrimer immobilized with Ti(IV) ions to
      functionalize nitrocellulose membrane, facilitating specific chelation of
      phosphoproteins from complex protein samples on the array. Globular, water
      soluble Ti(IV)-dendrimer allows the RP3A surface to be highly accessible to
      phosphoproteins multidimensionally, and the captured phosphoproteins were
      subsequently detected using the same validated antibodies as in regular reverse
      phase protein arrays. The novel chemical strategy demonstrated superior
      specificity (1:10 000), high sensitivity (fg level), and good quantitative nature
      ( R2 = 0.99) for measuring phosphoproteins. We further applied quantitative
      phosphoproteomics followed by RP3A to validate the phosphorylation status of a
      panel of phosphoproteins in response to environmental stresses in Arabidopsis.

PMID- 30103609
TI  - The resistance of zwitterionic peptide monolayers to biofouling.
AB  - Self-assembled monolayers (SAMs) are widely used in science and engineering, and
      recent progress has demonstrated the utility of zwitterionic peptides with
      alternating lysine (K) and glutamic acid (E) residues for antifouling purposes.
      Aiming at developing a peptide-based fouling-resistant SAM suitable for
      presentation of surface-attached pheromones for barnacle larvae, we have
      investigated five different peptide SAMs, where four are based on the EK motif,
      and the fifth was designed based on general principles for fouling resistance.
      The SAMs were formed by self-assembly onto gold substrates via cysteine residues
      on the peptides, and formation of SAMs was verified via ellipsometry,
      wettability, infrared reflection-absorption spectroscopy and cyclic voltammetry.
      Settlement of cypris larvae of the barnacle Balanus (=Amphibalanus) amphitrite,
      the target of pheromone studies, was tested. SAMs were also subjected to fouling
      assays using protein solutions, blood serum, and the bacterium Mycobacterium
      marinum. The results confirm the favourable antifouling properties of EK
      containing peptides in most of the assays, although this did not apply to the
      barnacle larvae settlement test, where settlement was low on only one of the
      peptide SAMs. The one peptide that had antifouling properties for barnacles did
      not contain a pheromone motif, and would not be susceptible to degredation by
      common serine proteases. We conclude that the otherwise broadly effective
      antifouling properties of EK-containing peptide SAMs is not directly applicable
      to barnacles, and that great care must be exercised in the design of peptide
      based SAMs for presentation of barnacle-specific ligands.

PMID- 30103610
TI  - New Pathway for Hot Electron Relaxation in Two-Dimensional Heterostructures.
AB  - Two-dimensional (2D) heterostructures composed of transition-metal dichalcogenide
      atomic layers are the new frontier for novel optoelectronic and photovoltaic
      device applications. Some key properties that make these materials appealing, yet
      are not well understood, are ultrafast hole/electron dynamics, interlayer energy
      transfer and the formation of interlayer hot excitons. Here, we study
      photoexcited electron/hole dynamics in a representative heterostructure, the
      MoS2/WSe2 interface, which exhibits type II band alignment. Employing time
      dependent density functional theory in the time domain, we observe ultrafast
      charge dynamics with lifetimes of tens to hundreds of femtoseconds. Most
      importantly, we report the discovery of an interfacial pathway in 2D
      heterostructures for the relaxation of photoexcited hot electrons through
      interlayer hopping, which is significantly faster than intralayer relaxation.
      This finding is of particular importance for understanding many experimentally
      observed photoinduced processes, including charge and energy transfer at an
      ultrafast time scale (<1 ps).

PMID- 30103611
TI  - One-Pot Synthesis of a Zwitterionic Small Molecule Bearing Disulfide Moiety for
      Antibiofouling Macro- and Nanoscale Gold Surfaces.
AB  - The goal of this study is to develop a simple one-pot method for the synthesis of
      a zwitterionic small molecule bearing disulfide moiety, which can effectively
      inhibit nonspecific protein adsorption on macroscopic and nanoscopic gold
      surfaces. To this end, the optimal molecular structure of a pyridine disulfide
      derivative was explored and a zwitterionic small molecule was successfully
      synthesized from the tertiary amine residue on the pyridine ring through a one
      pot method. The coating conditions of the synthesized zwitterionic molecules on
      the gold surface were optimized through contact angle measurements, and the
      strong interactions between the gold surface and the disulfide moiety of the
      zwitterion small molecule were confirmed by surface plasmon resonance (SPR)
      analysis and X-ray photoelectron spectroscopy. The antibiofouling properties of
      the coated gold surface were analyzed by fluorescence microscopic observations
      after contacting with FITC-labeled bovine serum albumin (BSA) and SPR sensor as
      contacting with BSA solution. In addition, the effect of zwitterion-coating on
      the salt stability of and protein adsorption on nanoscopic gold surfaces were
      examined through a NaCl stability test and BSA adsorption test, respectively.
      From the obtained results, it was confirmed that the simply synthesized
      zwitterionic small molecule was effective in inhibiting nonspecific protein
      adsorption on macroscopic and nanoscopic gold surfaces; further, it enhanced the
      salt stability of gold nanoparticle surfaces.

PMID- 30103612
TI  - Apathy in Preclinical Alzheimer's Disease: Psychometric Validation of the Apathy
      Evaluation Scale.
AB  - OBJECTIVES: The purpose of the present study was to validate the Apathy
      Evaluation Scale, self-rated version (AES-S), and assess the severity of apathy
      in a cognitively healthy middle-aged cohort at risk for Alzheimer's disease (AD).
      METHOD: Three hundred and sixteen middle-aged adults were selected to represent a
      subset of the Wisconsin Alzheimer's Disease Research Center Clinical Core: the
      Investigating Memory in People At-risk, Causes and Treatments cohort. RESULTS: An
      exploratory factor analysis (EFA) with varimax rotation identified 3 subscales:
      apathy, disinterest, and social withdrawal factors. Confirmatory factor analysis
      confirmed the EFA findings. Results indicated acceptable convergent and
      discriminant validity. The AES-S is a reliable instrument to quantify apathy in
      cognitively healthy middle-aged individuals at risk for AD. DISCUSSION: This
      study demonstrates the AES-S is a psychometrically sound measurement tool for
      assessing levels of apathy in a cognitively healthy middle-aged cohort at risk
      for AD.

PMID- 30103614
TI  - Manual Heating and Prevention of Radial Artery Occlusion.

PMID- 30103613
TI  - Application of High-Throughput Sequencing in the Diagnosis of Inherited
      Thrombocytopenia.
AB  - Inherited thrombocytopenia is a group of hereditary diseases with a reduction in
      platelet count as the main clinical manifestation. Clinically, there is an urgent
      need for a convenient and rapid diagnosis method. We introduced a high
      throughput, next-generation sequencing (NGS) platform into the routine diagnosis
      of patients with unexplained thrombocytopenia and analyzed the gene sequencing
      results to evaluate the value of NGS technology in the screening and diagnosis of
      inherited thrombocytopenia. From a cohort of 112 patients with thrombocytopenia,
      we screened 43 patients with hereditary features. For the blood samples of these
      43 patients, a gene sequencing platform for hemorrhagic and thrombotic diseases
      comprising 89 genes was used to perform gene detection using NGS technology. When
      we combined the screening results with clinical features and other findings, 15
      (34.9%) of 43patients were diagnosed with inherited thrombocytopenia. In
      addition, 19 pathogenic variants, including 8 previously unreported variants,
      were identified in these patients. Through the use of this detection platform, we
      expect to establish a more effective diagnostic approach to such disorders.

PMID- 30103615
TI  - Primary Middle Ear Mucosal Melanoma: Case Report and Comprehensive Literature
      Review of 21 Cases of Primary Middle Ear and Eustachian Tube Melanoma.
AB  - OBJECTIVE: To present a case of primary middle ear mucosal melanoma and perform a
      comprehensive literature review of middle ear and eustachian tube mucosal
      melanoma. PATIENT: A 61-year-old female presented with no prior history of
      melanoma and 3 months of aural fullness. A middle ear mass demonstrated primary
      mucosal melanoma. The mass extended from mesotympanum into hypotympanum,
      epitympanum, protympanum, eustachian tube, and mastoid antrum. Additionally, a
      nonenhancing expansile lesion of the petrous apex was noted on magnetic resonance
      imaging. INTERVENTION: Subtotal temporal bone resection with transotic approach
      to the petrous abnormality was performed. Postoperative adjuvant radiation and
      immunotherapy were given. RESULTS: Five months postoperatively, the patient
      developed an isolated cutaneous metastatic focus treated with wide local excision
      and has had no further evidence of recurrence to date. Upon comprehensive
      literature review, patients with primary middle ear melanomas (n = 10) present
      with otorrhea (50%), aural fullness (40%), and hearing loss (30%) most commonly,
      while hearing loss (81.8%) and aural fullness (54.5%) were the most common
      presenting symptoms for eustachian tube melanomas (n = 11). Patients were treated
      with combinations of surgery, radiation, and/or chemotherapy. Middle ear melanoma
      demonstrated particularly poor outcomes, with 70% mortality, 20% local
      recurrence, and 50% distant metastasis, whereas eustachian tube origin
      demonstrated 9.1%, 18.2%, and 36.4%, respectively. CONCLUSIONS: Middle ear and
      eustachian tube mucosal melanomas are exceedingly rare, with middle ear melanomas
      demonstrating a worse prognosis. Multimodality therapy is commonly used; however,
      outcomes are poor, with high mortality among affected patients.

PMID- 30103616
TI  - Recurrent sternal thymoma after thymectomy by video-assisted thoracic surgery.
AB  - An 81-year-old man underwent thymectomy by video-assisted thoracic surgery for a
      mediastinal tumor. The pathological diagnosis was Masaoka stage II type B3
      thymoma. Thirty-six months later, he presented with a growing mass on his
      anterior chest wall. Computed tomography showed a lobulated tumor in the sternum
      with bone destruction. Positron-emission tomography-computed tomography showed a
      maximal standardized uptake of 12.3 in the tumor. Core needle biopsy confirmed a
      metastatic sternal tumor from a type B3 thymoma. We partially resected the
      sternum and reconstructed the defect using an expanded polytetrafluoroethylene
      sheet. The patient has remained recurrence-free for 3 years after the second
      surgery.

PMID- 30103617
TI  - Thyrotropin levels and severity of symptoms in migraine patients of tertiary
      headache center.
AB  - Background The role of thyroid regulation in migraine is poorly understood, and
      data is contradictory. Objective To study the possible association of clinical
      features of migraine with patients' thyroid function. Patients and methods One
      hundred and thirty migraine patients of a tertiary headache center took part in
      an open-label, cross-sectional comparative study. The Migraine Disability
      Assessment questionnaire, Spielberger State-Trait Anxiety Inventory, Beck
      Depression Inventory, Vanderbilt's Questionnaire of Pain Management, Gothenburg
      Quality of Life Questionnaire and Migraine-Specific Quality of Life questionnaire
      were used. The effectiveness of the attacks' therapy was assessed according to
      the Migraine Assessment of Current Therapy questionnaire. Levels of thyrotropine
      (thyroid stimulating hormone), thyroxine, and triiodothyronine were studied by
      standard immune chemiluminescent method using the Immulite-2000 set. Results An
      inverse correlation between levels of thyroid stimulating hormone in serum and
      duration of headache attacks was revealed. The effectiveness of abortive therapy
      for attacks showed a statistically significant positive correlation with thyroid
      stimulating hormone level. Quality of life measured by a general quality of life
      questionnaire, as well as the functional and social indices of a migraine
      specific questionnaire, showed direct correlation with serum thyroid stimulating
      hormone. Conclusion These results show an association of a more severe clinical
      course of migraine with lower thyroid stimulating hormone levels.

PMID- 30103618
TI  - Reproducibility, longitudinal validity and interpretability of the Disease Burden
      Morbidity Assessment in people with chronic disease.
AB  - OBJECTIVE: To evaluate the reproducibility, longitudinal validity, and
      interpretability of the disease burden morbidity assessment in people with
      chronic conditions including multimorbidity. METHODS: The study was conducted
      using a longitudinal cohort design. A large consecutive sample of adult patients
      at an Australian community-based rehabilitation service was included with testing
      at baseline and three-month follow-up (testing longitudinal validity and
      interpretability). A smaller subsample of patients completed a one-week test
      retest (testing reproducibility). Outcome measures included the Disease Burden
      Morbidity Assessment and 36-item Short-Form Health Survey. Participants in the
      study received tailored, interdisciplinary intervention between baseline, and
      three-month follow-up but did not typically receive intervention between baseline
      and retest. RESULTS: The longitudinal validity and interpretability sample
      included 351 participants and the reproducibility sample included 56
      participants. Longitudinal validity and interpretability were generally supported
      with hypotheses supported or partly supported and a small percentage of lowest
      total scores for impact on daily activities (0.6% at baseline, 1.3% at three
      month follow-up). Reproducibility parameters were acceptable for the total score
      measuring impact on daily activities (e.g. ICC = 0.76). DISCUSSION:
      Reproducibility, longitudinal validity, and interpretability of the disease
      burden morbidity assessment were generally supported for community-based chronic
      disease patients.

PMID- 30103619
TI  - Barriers and Facilitators to Effective Inpatient Palliative Care Consultations: A
      Qualitative Analysis of Interviews With Palliative Care and Nonpalliative Care
      Providers.
AB  - OBJECTIVE: To identify factors that hinder or facilitate the palliative care
      consultation team's (PCCT) successful collaboration with other providers from the
      perspectives of both PCCT and nonpalliative specialists. METHODS: Qualitative
      study, including semistructured interviews with PCCT and nonpalliative care
      providers from various specialties at 4 Midwestern hospitals. Interviews were
      audio-recorded and transcribed into written text documents for thematic analysis.
      Palliative care consultation team (n = 19) and nonpalliative care providers (n =
      29) were interviewed at their respective hospital sites or via telephone.
      Palliative care consultation team providers included physicians, nurse
      practitioners, registered nurses, social workers, and one chaplain. Specialists
      included critical care physicians, surgeons, hospitalists, nephrologists,
      oncologists, and cardiologists. RESULTS: Six themes emerged reflecting barriers
      to and facilitators of successful collaboration between the PCCT and other
      providers. Primary barriers included attitudes about palliative care, lack of
      knowledge about the role of the PCCT, and patient and family resistance.
      Facilitators included marketing of the palliative care service and education
      about the expertise of the PCCT. CONCLUSION: In order to engage in more effective
      collaboration with other specialty providers, the PCCT may consider strategies
      including structured educational interventions, increased visibility in the
      hospital, and active marketing of the utility of palliative care across
      disciplines.

PMID- 30103620
TI  - Variability in Retronasal Odor Identification Among Patients With Chronic
      Rhinosinusitis.
AB  - Background Retronasal olfaction is important in flavor detection and enjoyment.
      The ability to identify specific individual retronasal odors may play a role in
      quality of life for patients with chronic rhinosinusitis (CRS). Objective To
      identify patterns and improve understanding of retronasal identification of
      individual odors in CRS patients. Methods Patients diagnosed with CRS underwent
      retronasal and orthonasal (Sniffin' Sticks) olfactory testing and taste testing
      (taste strips). Retronasal identification was tested with presentation of
      flavored powders on the posterior tongue. Retronasal identification for
      individual odors was compared with results of orthonasal and taste testing.
      Results Seventy participants were evaluated. Retronasal identification correlated
      with orthonasal identification and discrimination for most individual odors.
      Among all patients, cinnamon and apple were identified better retronasally and
      banana better orthonasally ( P < .05). Anosmics identified retronasal orange,
      cinnamon, mushroom, coffee, smoked ham, peach, ginger, grape, and cheese more
      than would be expected by chance for a forced-choice paradigm with 3 distractor
      items ( P < .05), and this was independent of objective taste function for most
      odors. Conclusion Retronasal and orthonasal identification of most odors
      correlate in CRS patients; however, patients with anosmia can still identify
      certain retronasal odors more often than expected. These odors do not appear to
      stimulate gustatory pathways and may involve trigeminal stimulation.
      Understanding preserved retronasal neural stimuli may allow providers to improve
      eating-related quality of life in these patients.

PMID- 30103621
TI  - A qualitative study of patient-centered goal-setting in geriatric rehabilitation:
      patient and professional perspectives.
AB  - OBJECTIVE: To characterize how rehabilitation goals of older patients change over
      time and to explore professionals' attitudes toward patient-centered goal-setting
      and their perspectives on rehabilitation goals. DESIGN: Qualitative interview
      study. SETTING: Three geriatric rehabilitation centers. SUBJECTS: Ten patients
      (aged ? 80), who had recently received inpatient geriatric rehabilitation, and
      seven professionals were purposively recruited. METHODS: Semi-structured
      interviews. Patients were interviewed in the third or fourth week after discharge
      from inpatient rehabilitation, to reflect on their inpatient goals and to
      investigate long-term goals now that they were at home. A thematic analysis was
      performed. RESULTS: During inpatient rehabilitation, participants' main goals
      were regaining independence in self-care activities and going home. Post
      discharge, patients were not at their baseline functioning level. Rehabilitation
      goals appeared to shift over time, and once at home, patients formulated more
      ambitious rehabilitation goals that were related to regaining full independence
      and being able to perform activities. Although professionals thought goal-setting
      together with the patient is important, they also stated that older individuals
      often are either unable to formulate goals or they set unrealistic ones. In
      addition, professionals indicated that goals have to be related to discharge
      criteria, such as performing basic self-care activities, and rehabilitation
      revolves around getting patients ready for discharge. CONCLUSION: During
      inpatient rehabilitation, patient goals are related to going home. After
      discharge, patients have ambitious goals, related to their premorbid functioning
      level. Rehabilitation services should distinguish between goals that are
      important while patients are inpatient and goals that are important after
      discharge.

PMID- 30103622
TI  - Effect of Patiromer in Hyperkalemic Patients Taking and Not Taking RAAS
      Inhibitors.
AB  - INTRODUCTION: Hyperkalemia (potassium >5.0 mEq/L) affects heart failure patients
      with renal disease regardless of the use of renin-angiotensin-aldosterone system
      inhibitors (RAASi). The open-label TOURMALINE study showed that patiromer, a
      sodium-free, nonabsorbed potassium binder, lowers serum potassium of hyperkalemic
      patients similarly when given with or without food; unlike prior studies,
      patients were not required to be taking RAASi. We conducted post hoc analyses to
      provide the first report of patiromer in patients not taking RAASi. METHODS:
      Hyperkalemic patients received patiromer, 8.4 g/d to start, adjusted to achieve
      and maintain serum potassium of 3.8 to 5.0 mEq/L. If taking RAASi, stable doses
      were required. The primary end point was the proportion of patients with serum
      potassium 3.8 to 5.0 mEq/L at week 3 or 4. This analysis presents data by
      patients taking or not taking RAASi. RESULTS: Demographics and baseline
      characteristics were similar in patients taking (n = 67) and not taking RAASi (n
      = 45). Baseline mean (SD) serum potassium was 5.37 (0.37) mEq/L and 5.42 (0.43)
      mEq/L in patients taking and not taking RAASi, respectively. Mean (SD) daily
      patiromer doses were similar (10.7 [3.2] and 11.5 [4.0] g, respectively). The
      primary end point was achieved in 85% (95% confidence interval [CI]: 74-93) of
      patients taking RAASi and in 84% (95% CI: 71-94) of patients not taking RAASi.
      From baseline to week 4, the mean (SE) change in serum potassium was -0.67 (0.08)
      mEq/L in patients taking RAASi and -0.56 (0.10) mEq/L in patients not taking
      RAASi (both P < .0001 vs baseline, P = nonsignificant between groups). Adverse
      events were reported in 26 (39%) patients taking RAASi and 25 (54%) not taking
      RAASi; the most common adverse event was diarrhea (2% and 11%, respectively; no
      cases were severe). Five patients (2 taking RAASi) reported 6 serious adverse
      events; none considered related to patiromer. CONCLUSIONS: Patiromer was
      effective and generally well-tolerated for hyperkalemia treatment, whether or not
      patients were taking RAAS inhibitors.

PMID- 30103623
TI  - Clinica Comunitaria Esperanza: Strategy for Health Promotion and Engagement With
      Hispanic Communities.
AB  - A 2009 community needs assessment highlighted the health care gap facing Hispanic
      residents in Hampton, Virginia, one of the major cities served by Eastern
      Virginia Medical School (EVMS). Survey respondents indicated the following as
      health care barriers: language, lack of knowledge, and lack of a community health
      center. EVMS students worked to bridge the health care gap between existing needs
      and services by establishing and maintaining the Clinica Comunitaria Esperanza, a
      culturally and linguistically competent student-run free clinic serving uninsured
      Hispanics in the Hampton Roads area. This article provides a model for engaging
      effectively with a priority population through partnerships that facilitate
      understanding of the community concerns, values, culture, and existing local
      resources that serve as determinants of health. This article further illustrates
      how the integration of two preexisting EVMS programs, the HOPES (Health Outreach
      Partnership of EVMS Students) Clinic and the Medical Spanish program, has
      supported the development and sustainability of Clinica Comunitaria Esperanza.
      The HOPES Clinic is a student-run free clinic that provides both general and
      specialty care to uninsured patients. EVMS' Medical Spanish program is a
      longitudinal service learning initiative composed of medical students, faculty,
      and staff dedicated to providing inclusive health care to meet the needs of the
      local Spanish-speaking community.

PMID- 30103624
TI  - Approaches to rapid acting insulin intensification in patients with type 2
      diabetes mellitus not achieving glycemic targets.
AB  - Type 2 diabetes mellitus (T2DM) is a growing problem in the USA, affecting 30.3
      million Americans, or 9.4% of the US population. Given that T2DM is a progressive
      disease, intensification of rapid acting insulin (RAI) to address hyperglycaemia
      is often required. The American Diabetes Association and the European Association
      for the Study of Diabetes recommend individualizing the treatment approach to
      glucose control, considering factors such as age, health behaviours,
      comorbidities and life expectancy. There are several validated treatment
      algorithms in the literature, which can be helpful for providing guidance on
      initiation of RAI while simultaneously considering patient preferences and
      clinical needs during treatment intensification. This paper provides expert
      recommendations on prandial insulin regimens and how to use treatment algorithms
      to promote better glucose control through best practice guidelines. To help
      patients reach HbA1c targets through treatment intensification, the FullSTEP,
      SimpleSTEP, ExtraSTEP and AUTONOMY algorithms are discussed in this paper. KEY
      MESSAGES Clinical inertia should be prevented with timely intensification of
      therapy when HbA1c levels are greater than 7% (or rising above a patient's
      individual target) according to national guidelines. Increased personalization in
      the intensification of T2D treatment is necessary to improve HbA1c targets while
      addressing risk of hypoglycaemia, concern about weight gain, and overall health
      goals. Healthcare providers are encouraged to address glycaemic control with a
      variety of strategies, including prandial insulin, while developing evidence
      based treatment plans on the basis of algorithms discussed in the literature.

PMID- 30103625
TI  - Go with the FLOW: Implementation of a psychological skills intervention in an
      exercise program for post-bariatric surgery patients.
AB  - Bariatric surgery is an effective obesity treatment; however, most individuals
      regain weight following surgery. Following a Lifestyle of Wellness (FLOW) is a
      psychological skills intervention with strategies designed to increase self
      efficacy and promote living a healthy lifestyle including regular physical
      activity. Eleven participants completed FLOW. Results indicated participants
      enjoyed the program and intended to continue this lifestyle upon program
      completion. Interviews indicated FLOW was effective for improving self
      perceptions, and exercise motivation. The most effective sessions were goal
      setting, future planning, and stress management. Suggestions for program
      improvement were provided. This information can be used to improve the FLOW
      program and for implementation into other settings.

PMID- 30103627
TI  - Comparison of the rates of stroke and acute coronary events in northern France.

PMID- 30103626
TI  - Chitosan-based nanoparticles as drug delivery systems: a review on two decades of
      research.
AB  - Chitosan (CS) is one of the most functional natural biopolymer widely used in the
      pharmaceutical field due to its biocompatibility and biodegradability. These
      privileges lead to its application in the synthesis of nanoparticles for the drug
      during the last two decades. This article gives rise to a general review of the
      different chitosan nanoparticles (CSNPs) preparation techniques: Ionic gelation,
      emulsion cross-linking, spray-drying, emulsion-droplet coalescence method,
      nanoprecipitation, reverse micellar method, desolvation method, modified ionic
      gelation with radial polymerisation and emulsion solvent diffusion, from the
      point of view of the methodological and mechanistic aspects involved. The
      physicochemical behaviour of CSNPs including drug loading, drug release,
      particles size, zeta potential and stability are briefly discussed. This review
      also directs to bring an outline of the major applications of CSNPs in drug
      delivery according to drug and route of administration. Finally, derivatives of
      CSNPs and CS nano-complexes are also discussed.

PMID- 30103628
TI  - Haptoglobin and haptoglobin genotypes in diabetes: A silver bullet to identify
      the responders to antioxidant therapy?

PMID- 30103629
TI  - Ambulatory cardiac rehabilitation facilities should be present in every
      cardiology department.

PMID- 30103630
TI  - Physical fitness is a modifiable predictor of early cardiovascular death: A 35
      year follow-up study of 2014 healthy middle-aged men.
AB  - Background Physical fitness has been shown to predict cardiovascular death during
      long-term follow-up. In the present study we aimed to investigate how physical
      fitness and other cardiovascular risk factors at middle-age influenced the risk
      of cardiovascular death during the early (0-11 years), intermediate (12-23 years)
      and late (24-35 years) parts of a 35-year observation period. Methods and results
      Age-adjusted physical fitness was calculated in 2014 apparently healthy, middle
      aged men after maximal bicycle electrocardiogram-tests in 1972-1975 (Survey 1)
      and 1979-1982 (Survey 2). The men were assessed through 35 years after Survey 1,
      and 28 years after Survey 2 by Cox proportional hazards models. Low Survey 1
      physical fitness was independently associated with increased risks of early and
      intermediate, but not late, cardiovascular death. Survey 1 to Survey 2 change in
      physical fitness, age, smoking status, systolic blood pressure and cholesterol
      impacted cardiovascular death risks in all periods. Family history of coronary
      heart disease impacted early and intermediate, but not late, cardiovascular
      death. Conclusions Most classical cardiovascular risk factors were strong
      predictors of early, intermediate and late cardiovascular death. Physical fitness
      measured at median age 50 years was independently associated with risk of early
      cardiovascular death, but the association weakened as time progressed. Change in
      physical fitness during middle-age impacted cardiovascular death risk in a full
      lifetime perspective. Thus, our data suggest that physical fitness is a
      modifiable cardiovascular risk factor with limited duration in contrast to the
      sustained impact of smoking, blood pressure and cholesterol on cardiovascular
      mortality.

PMID- 30103631
TI  - Total arterial compliance: An underestimated biomarker.

PMID- 30103632
TI  - Relationship between preoperative patient-reported outcomes and hospital length
      of stay: a prospective cohort study of general surgery patients in Vancouver,
      Canada.
AB  - OBJECTIVES: As an aging population drives more demand for elective inpatient
      surgery, one approach to reducing length of stay is enhanced evaluation of
      patients' preoperative health status. The objective of this research was to
      determine whether patient-reported outcome measures collected preoperatively can
      identify patients at risk for longer lengths of stay. METHODS: This study was
      based on a prospectively recruited cohort of patients who were scheduled for
      elective inpatient general surgery in Vancouver, Canada. All participants
      completed a number of patient-reported outcome measures preoperatively, including
      the EQ-5D for general health status, the Patient Health Questionnaire (PHQ-9) for
      depression, and the pain intensity (P), interference with enjoyment of life (E),
      and interference with general activity (G), known as the PEG, for pain. Patient
      reported outcome data were linked to hospital discharge summaries. Multivariate
      regression was performed to estimate risk of longer lengths of stay, adjusting
      for patient and clinical characteristics. The primary outcome was length of stay
      and its associated cost. Data collection took place between October 2012 and
      November 2016. RESULTS: Participation among the population of 2307 eligible
      patients was 50.5%, providing 1165 participants. Preoperative patient-reported
      outcomes were not concordant with hospital reported diagnoses of depression or
      pain. Patients' preoperative depression and pain scores were independently
      positively associated with longer length of stay after adjusting for patient
      level characteristics. Patients whose PHQ-9 score was 10, representing clinically
      significant depression, were estimated to have a 1.53 day longer hospitalization,
      which was associated with an estimated incremental hospital cost of $1667.
      CONCLUSIONS: Preoperative self-reported assessment of depression and pain can
      assist with identifying patients at higher risk of longer lengths of stay.
      Patient's self-reported preoperative measures of depression and pain should be
      incorporated into patient pathways. They provide opportunities for improving
      management of general surgery patients and possibly play a role in aligning
      hospital funding with patients' needs.

PMID- 30103633
TI  - Effect of acetamiprid on the immature murine testes.
AB  - Neonicotinoids, such as acetamiprid (ACE), a pesticide used worldwide, are
      believed to be safe for human use. These molecules are structurally similar to
      nicotine, act as nicotinic acetylcholine receptor (nAChR) agonists, and were
      shown to be associated with neuromuscular and reproductive disorders, but these
      experiments were primarily performed in mature animals. In this study, the
      effects of ACE on the testes of immature mice were examined. The exposure of 3
      week-old mice to ACE-containing water for 180 days led to a decrease in body
      weight and mildly affected spermatogenesis. Additionally, the expression of
      testosterone-metabolism genes, nAChR subunit genes, and proliferation-associated
      genes decreased in the testes of ACE-treated mice. Our results show that immature
      rodents may be less sensitive to ACE than mature ones, that mice may be more
      likely to accumulate ACE than rats, and that the development of disorders may be
      affected by the accumulation of ACE in the testes.

PMID- 30103634
TI  - Health hazards of nanoparticles: understanding the toxicity mechanism of
      nanosized ZnO in cosmetic products.
AB  - In recent years, nanoparticles are being used extensively in personal healthcare
      products such as cosmetics, sunscreens, soaps, and shampoos. Particularly, metal
      oxide nanoparticles are gaining competence as key industrial constituents,
      progressing toward a remarkable rise in their applications. Zinc oxide and
      titanium oxide nanoparticles are the most commonly employed metal oxide
      nanoparticles in sunscreens, ointments, foot care, and over the counter topical
      products. Dermal exposure to these metal oxides predominantly occurs through
      explicit use of cosmetic products and airway exposure to nanoparticle dusts is
      primarily mediated via occupational exposure. There is a compelling need to
      understand the toxicity effects of nanoparticles which can easily enter the cells
      and induce oxidative stress. Consequently, these products have become a direct
      source of pollution in the environment and thereby greatly impact our ecosystem.
      A complete understanding of the toxicity mechanism of nano-ZnO is intended to
      resolve whether and to what extent such nanoparticles may pose a threat to the
      environment and to human beings. In this review article, we have discussed the
      characteristics of metal oxide nanoparticles and its applications in the cosmetic
      industry. We have also highlighted about their toxicity effects and their impact
      on human health.

PMID- 30103635
TI  - Increased maternal C1q/TNF-related protein-1 (CTRP-1) serum levels in pregnancies
      with preeclampsia.
AB  - OBJECTIVE: Metabolic changes and inflammation are involved in the pathogenesis of
      preeclampsia. Complement C1q tumor necrosis factor-related protein-1 (CTRP-1) is
      a pleiotropic molecule that possesses insulin-sensitizing effects and is also
      involved in lipid metabolism and inflammatory responses. The aim of the study was
      to investigate CTRP-1 levels in pregnancies with preeclampsia. MATERIAL AND
      METHODS: Serum concentrations of CTRP-1 were measured in 29 pregnant women with
      early-onset preeclampsia (EOPE), 24 pregnant women with late-onset preeclampsia
      (LOPE), and 26 women with uncomplicated pregnancies using an enzyme-linked
      immunosorbent assay method. RESULTS: Patients with both EOPE and LOPE had
      significantly higher serum concentrations of CTRP-1 compared to the healthy
      controls (p < .001). However, no significant difference was found between the
      EOPE and LOPE groups regarding CTRP-1 levels (p = 1.000). Correlation analysis
      showed that CTRP-1 levels were positively correlated with systolic blood pressure
      (p < .001), diastolic blood pressure (p < .001), and mean UtA PI (p < .001) but
      negatively correlated with gestational age at delivery (p = .001) and birth
      weight (p < .001). CONCLUSIONS: Serum CTRP-1 levels were significantly higher in
      patients with both EOPE and LOPE than in healthy pregnant women.

PMID- 30103636
TI  - Facial Involvement in Dermatitis Herpetiformis: A Case Report and Review of the
      Literature.
AB  - Dermatitis herpetiformis is a cutaneous manifestation of celiac disease that
      classically presents as a symmetric pruritic vesicular eruption on extensor
      surfaces. Typical locations include elbows, knees, and buttocks. Facial
      involvement has been reported rarely. Here, we report a case of a 44-year-old
      woman with dermatitis herpetiformis presenting as pruritic vesicles on the face
      that had previously been misdiagnosed as allergic contact dermatitis. Diagnosis
      was confirmed with direct immunofluorescence demonstrating granular IgA in the
      papillary dermis. This eruption cleared with topical dapsone 5% gel and a gluten
      free diet. We report this case to raise awareness of facial involvement in
      dermatitis herpetiformis as well as the possibility of topical dapsone as a
      therapeutic option.

PMID- 30103637
TI  - Positive Interactive Engagement (PIE): A pilot qualitative case study evaluation
      of a person-centred dementia care programme based on Montessori principles.
AB  - Altered behaviour associated with dementia can present a number of challenges in
      the provision of care within both community and residential aged care settings.
      This paper presents a qualitative case study investigation of the implementation
      of the Positive Interactive Engagement programme within a residential aged care
      setting. The Positive Interactive Engagement programme incorporates non
      pharmacological sensory techniques that have been informed by a person-centred,
      Montessori approach. Face-to-face semi-structured interviews with workers at a
      residential aged care facility in South Australia yielded seven case studies.
      Data were thematically analysed both within and between cases. Our data indicate
      the programme demonstrates underlying Montessori principles and supports
      participant behaviour change, with a noted reduction in 'disruptive' behaviours
      and increased social connection amongst participants. Programme staff report
      increased job satisfaction. The Positive Interactive Engagement programme offers
      a model that demonstrates encouraging outcomes, and further research would be
      useful in ascertaining whether these outcomes translate to quantifiable
      improvements in the quality of life for people with dementia in a residential
      aged care setting.

PMID- 30103638
TI  - Advances in medical therapy for pericardial diseases.
AB  - INTRODUCTION: Medical therapy of pericardial diseases is moving forward to the
      road of evidence-based medicine and has improved in the last years because of the
      first randomized clinical trials in the area as well as new therapeutic options
      for recurrent pericarditis. Areas covered: The present review will focus on more
      recent advances with a special emphasis on the treatment of pericarditis, the
      area with more significant improvements in the last years. Medline/Pubmed Library
      were systematically screened with two specific key searches: 'pericarditis AND
      therapy' and 'pericardial effusion AND therapy'. The search was restricted to
      articles published in the last 5 years, in order to select the latest novelties
      in medical treatment and was restricted to 'human' studies and papers in English.
      Expert commentary: The anti-inflammatory therapy of pericarditis has been now
      well defined with first-line agents represented by nonsteroidal anti-inflammatory
      drugs plus colchicine, low-dose corticosteroids with slow tapering as second-line
      agents and for specific indications (e.g. specific systemic inflammatory
      diseases, renal failure, pregnancy, patients with interfering therapies such as
      oral anticoagulants), and third-line options in case of multiple recurrences
      (e.g. azathioprine, intravenous immunoglobulins, and especially anakinra).

PMID- 30103639
TI  - Genotoxic effects of imidacloprid in human lymphoblastoid TK6 cells.
AB  - Among neonicotinoid insecticides, the fastest growing class of insecticides
      worldwide over the past decade, imidacloprid (IMI) is the most widely used one.
      The effects of IMI on human health, especially on genetic toxicity have gradually
      aroused more attention. In this study, a combined in vitro approach employing the
      thymidine kinase (TK) gene mutation assay, the comet assay and the micronucleus
      test was taken to assess the genotoxicity of IMI. The mechanism behind IMI was
      also explored by measuring reactive oxygen species (ROS) in the human
      lymphoblastoid TK6 cells. The cells were treated with 0.01, 0.1, 1, 5, and 10
      MUg/mL IMI, and ROS generation was measured by the use of 2,7,-dichlorofluorescin
      diacetate (DCFH-DA) assay. IMI significantly increased the micronucleus (MN)
      frequency, TK mutations and DNA damage with a dose-effect relationship, and the
      lowest effective concentration in those tests was 0.1 MUg/mL. However, no obvious
      change of intracellular ROS was observed for any concentrations. The results
      indicate that IMI has potential genotoxic effects on TK6 cells, but ROS does not
      seem to be involved as a mechanism of genotoxicity under the experimental
      conditions.

PMID- 30103641
TI  - The impact of extremes of maternal age on maternal and neonatal pregnancy
      outcomes in women with pregestational diabetes mellitus.
AB  - BACKGROUND: . Diabetes mellitus (DM) during pregnancy increases the risk for many
      complications such as preeclampsia and cesarean section. Teen (age <20) and
      advanced maternal age (AMA, age >=35) pregnancies are both at increased risk for
      maternal and neonatal morbidity and mortality. Understanding the risks and
      complications unique to teen and AMA women with pregestational DM is imperative
      to providing care and improving outcomes. OBJECTIVE: . This study sought to
      determine how maternal and neonatal outcomes are affected by pregestational DM in
      teen and AMA pregnancies. STUDY DESIGN: . This is a retrospective cohort study of
      1.58 million pregnancies in California from 2005 through 2008s, of which 10,034
      diabetic women with nonanomalous, singleton pregnancies were identified. Women
      with gestational DM were excluded. Maternal outcomes examined include
      preeclampsia, placental abruption, chorioamnionitis, preterm delivery, and
      cesarean section. Neonatal outcomes include size for gestational age, birth
      weight >4000 g, shoulder dystocia, brachial plexus injury, jaundice, and
      intrauterine fetal demise (IUFD). Multivariate regression analyses and chi
      squared test were used for statistical comparisons and a p-value of less than .05
      was used to indicate statistical significance. RESULTS: . Compared to women of
      age 20-34 years with pregestational DM as the reference group, women <20 years
      old with DM had higher rates of preeclampsia (aOR 1.72; 95% CI 1.29-2.29; p-value
      < .001) and lower rates of cesarean delivery (aOR 0.63; 95% CI 0.47-0.85; p <
      .001). Neonates of teen mothers were more likely to be large for gestational age
      (LGA; > 90%ile; aOR 1.60; 95% CI 1.14-2.23; p = .006), whereas neonates in the
      maternal age category of 35-39 years had lower rates of LGA >90%ile (aOR 0.81;
      95% CI 0.70-0.92; p = .001). Odds of IUFD were greatest in women age 35-39 years
      old (aOR 1.73; 95% CI 1.05-2.85; p = .031). Analysis examining women >40 years
      old showed no statistically significant difference in outcomes. CONCLUSION:
      Pregnancy outcomes in women with pregestational diabetes differ depending on
      maternal age category. Teens are at higher risk for preeclampsia and LGA
      neonates, but at lower risk for cesarean. Women aged 35-39 years are at higher
      risk for cesarean delivery, are less likely to have LGA neonates, and more likely
      to experience IUFD. Understanding the etiologies behind these differences may
      lead to improvements in these clinical outcomes.

PMID- 30103640
TI  - Oxymatrine exhibits anti-tumor activity in gastric cancer through inhibition of
      IL-21R-mediated JAK2/STAT3 pathway.
AB  - Oxymatrine (OMT) as a type of alkaloids collected from Sophora flavescens Ait
      exerts some biological functions including anticancer properties. Here, we
      investigated the therapeutic effects of OMT in gastric cancer cells (HGC 27 and
      AGS). As a result, the exposure of gastric cancer (GC) cells to OMT contributed
      to the suppression of cell proliferation and invasion. Interleukin 21 receptor
      (IL-21R) was identified to be differentially expressed between OMT treatment
      group (4 mg/mL) and control group (0 mg/mL), and knockdown of IL-21R repressed
      cell proliferation and invasion via inactivation of the JAK2/STAT3 pathway. The
      rescue experiment showed that IL-21R overexpression attenuated the anti-tumor
      effects of OMT through activation of the JAK2/STAT3 pathway. Moreover, the
      expression of IL-21R was significantly upregulated in GC samples compared with
      the adjacent normal tissues and associated with overall survival (OS) and tumor
      recurrence of GC patients. Taken together, in this study, we evaluated the anti
      tumor effects of OMT on GC by investigating proliferation and invasion ability
      changes, and our findings show that OMT exhibits effects via regulation of
      JAK/STAT signaling pathway. Through the mechanism study, we may enlighten the
      potential therapeutic target for treatment of GC.

PMID- 30103642
TI  - Discriminative ability and clinical utility of the Timed Up and Go (TUG) in
      identifying falls risk in people with multiple sclerosis: a prospective cohort
      study.
AB  - OBJECTIVE: To investigate discriminative ability and clinical utility of the
      Timed Up and Go under single- and dual-task conditions between fallers and non
      fallers in multiple sclerosis (MS). DESIGN: Prospective cohort study. SETTING:
      Neurology service in a tertiary hospital. SUBJECTS: Participants were 101 people
      with MS and Expanded Disability Status Scale score of 3-6.5. One participant
      withdrew after the baseline assessment, and hence the data were analysed for 100
      participants. INTERVENTIONS: No specific intervention. MAIN MEASURES: Timed Up
      and Go and Timed Up and Go-Cognitive. Three-month prospective diaries recorded
      falls. RESULTS: Mean age was 52.6 (SD 10.7) and 66 were female. Majority of the
      participants had progressive MS (72) and 73 used a walking aid; 56 participants
      recorded 791 falls. The area under the receiver operating characteristic curve
      values for Timed Up and Go and Timed Up and Go-Cognitive in distinguishing
      fallers (person with ?1 fall) from non-fallers are 0.60 and 0.57, respectively,
      and in distinguishing multiple fallers (?2 falls) the values are 0.46 and 0.43. A
      Timed Up and Go score of ?9 seconds has a sensitivity of 0.82 and a specificity
      of 0.34 to identify fallers and a sensitivity of 0.79 and a specificity of 0.27
      to identify multiple fallers. A Timed Up and Go-Cognitive score of ?11 seconds
      has a sensitivity of 0.77 and a specificity of 0.30 to identify fallers and a
      sensitivity of 0.71 and a specificity of 0.26 to identify multiple fallers.
      CONCLUSION: The Timed Up and Go and Timed Up and Go-Cognitive do not demonstrate
      sufficient clinical utility or discriminative ability for assessing falls risk in
      MS.

PMID- 30103644
TI  - Ureteric stricture rates and management after robot-assisted radical cystectomy:
      a single-centre observational study.
AB  - OBJECTIVE: Benign ureterointestinal anastomosis (BUIA) stricture is a recognized
      complication after open radical cystectomy. The evidence for stricture rates
      following robot-assisted radical cystectomy (RARC) is limited. This article
      reports stricture rates from a single high-volume RARC centre. MATERIALS AND
      METHODS: Between December 2003 and December 2015, 371 patients underwent RARC
      with a totally intracorporeal urinary diversion. All patients received a ureteric
      anastomosis utilizing the 'Wallace plate' with a running suture technique.
      Monofilament suture was used in the first 81 patients (22%) and a barbed suture
      (QuillTM) in the remaining 290 patients (78%). RESULTS: Median follow-up was 33
      months and minimum follow-up was 7.9 months. The median time to stricture
      formation was 165 days (range 10-495 days). Twenty-four patients (6.5%) developed
      BUIA strictures. Six of 81 patients (7.4%) in the monofilament group and 18 of
      290 (6.2%) in the barbed suture group developed strictures (p = .22). Fifteen
      patients (63%) had a stricture on the left side, seven (29%) on the right side
      and two patients (8%) developed bilateral ureteric strictures (p = .002).
      Strictures occurred in 11 of 131 patients (8.3%) with an orthotopic neobladder
      and 13 of 240 (5.4%) with an ileal-conduit urinary diversion (p = .17).
      CONCLUSIONS: The overall incidence of ureteric strictures is low in patients
      undergoing RARC with totally intracorporeal urinary diversion. Strictures were
      more common on the left side, which has been described in open series and is
      probably related to the increased mobilization on the left side required to cross
      the ureter to the right side.

PMID- 30103643
TI  - Engaging Men in Psychological Treatment: A Scoping Review.
AB  - Tailoring psychological treatments to men's specific needs has been a topic of
      concern for decades given evidence that many men are reticent to seek
      professional health care. However, existing literature providing clinical
      recommendations for engaging men in psychological treatments is diffuse. The aim
      of this scoping review was to provide a comprehensive summary of recommendations
      for how to engage men in psychological treatment. Four electronic databases
      (MEDLINE, PubMed, CINAHL, PsycINFO) were searched for articles published between
      2000 and 2017. Titles and abstracts were reviewed; data extracted and synthesized
      thematically. Of 3,627 citations identified, 46 met the inclusion criteria.
      Thirty articles (65%) were reviews or commentaries; 23 (50%) provided broad
      recommendations for working with all men. Findings indicate providing male
      appropriate psychological treatment requires clinicians to consider the impact of
      masculine socialization on their client and themselves, and how gender norms may
      impact clinical engagement and outcomes. Existing literature also emphasized
      specific process micro-skills (e.g., self-disclosure, normalizing), language
      adaption (e.g., male-oriented metaphors) and treatment styles most engaging for
      men (e.g., collaborative, transparent, action-oriented, goal-focused). Presented
      are clinical recommendations for how to engage men in psychological treatments
      including paying attention to tapping the strengths of multiple masculinities
      coexisting within and across men. Our review suggests more empirically informed
      tailored interventions are needed, along with formal program evaluations to
      advance the evidence base.

PMID- 30103645
TI  - Culture and neuroscience: How Japanese and European Canadians process social
      context in close and acquaintance relationships.
AB  - Recent cultural psychology findings suggest that social orientation affects
      neural social attention. Whereas independent cultures process people as separate
      from social context, interdependent cultures process people as dependent on
      social context. This research expands upon these findings, investigating what
      role culture plays in people's neural processing of social context for two
      relationship contexts, close and acquaintance relationships. To investigate, we
      had European Canadian and Japanese participants rate the emotions of center faces
      in face lineups while collecting ERP data. Lineups were either congruent, with
      all faces showing similar emotions, or incongruent, with center face emotions
      differing from background faces. To investigate relationship types, we framed
      face lineups to be in close or acquaintance relationships. We found that for
      acquaintances, only Japanese processed incongruent social context as meaningful,
      as seen through N400 incongruity effects. Contrasting with these patterns, only
      European Canadians showed N400 incongruity effects for close relationships. These
      patterns were seen whether or not the two groups noticed the emotional conflict,
      as seen by N2 incongruity effects. Finally, we found that social orientation was
      differentially related to the neural incongruity effects for the two
      relationships. These findings further elucidate the nuances of how culture
      affects neural social attention.

PMID- 30103646
TI  - Corticosteroid dose and the risk of opportunistic infection in a national
      systemic lupus erythematosus cohort.
AB  - Objective This study investigated whether the incidence of opportunistic
      infection differed in systemic lupus erythematosus patients who received
      different doses of corticosteroids. Methods We included patients with diagnosed
      systemic lupus erythematosus from 1997 to 2010 using Taiwan national health
      insurance data. The index day for systemic lupus erythematosus patients was 3
      months after the systemic lupus erythematosus diagnosis. A non-steroid cohort was
      matched 4:1 with the steroid cohort according to age, sex and index day. The end
      of the follow-up period was the day of opportunistic infection diagnosis, 1 year
      after the index day, or death. Results The overall cumulative incidence of
      opportunistic infection was 136-fold higher in the steroid cohort than in the non
      steroid cohort. The adjusted hazard ratio for developing mycobacterium infection
      in the steroid cohort was 11, and the adjusted hazard ratio for developing herpes
      zoster was 43.6 compared to the non-steroid cohort after adjusting for
      immunosuppressive agents and comorbidities. The adjusted hazard ratio value for
      opportunistic infection was 1.40 (95% confidence interval (CI) 0.78-2.51) for a
      daily prednisone-equivalent dose of 7.5-15 mg, 1.72 (95% CI 1.02-2.91) for 15-30
      mg, 1.96 (95% CI 1.17-3.28) for 30-60 mg and 2.24 (95% CI 1.26-4.00) for over 60
      mg compared with low-dose steroids (<7.5 mg). Conclusion This study confirmed
      that the risk of opportunistic infection is higher in systemic lupus
      erythematosus patients treated with steroids in the first 3 months after
      diagnosis versus those not treated with steroids. Medium and high doses were
      associated with a higher risk of opportunistic infection compared with low doses.
      However, there was no controlling for disease activity, making it hard to know if
      increases in infection were due to disease itself or corticosteroids.

PMID- 30103647
TI  - Longitudinal evaluation of diffusion tensor imaging and cognition in systemic
      lupus erythematosus.
AB  - Objective This pilot study aimed to examine longitudinal changes in brain
      structure and function in patients with systemic lupus erythematosus (SLE) using
      diffusion tensor imaging (DTI) and neuropsychological testing. Methods Fifteen
      female SLE patients with no history of major neuropsychiatric (NP) manifestations
      had brain magnetic resonance imaging (MRI) with DTI at baseline and approximately
      1.5 years later. At the same time points, a standardized battery of cognitive
      tests yielding a global cognitive impairment index (CII) was administered. At
      baseline, the SLE patients had mean age of 34.0 years (SD = 11.4), mean education
      of 14.9 years (SD = 2.1), and mean disease duration of 121.5 months (SD = 106.5).
      The MRI images were acquired with a 3T GE MRI scanner. A DTI sequence with 33
      diffusion directions and b-value of 800 s/mm2 was used. Image acquisition time
      was about 10 minutes. Results No significant change in cognitive dysfunction
      (from the CII) was detected. Clinically evaluated MRI scans remained essentially
      unchanged, with 62% considered normal at both times, and the remainder showing
      white matter (WM) hyperintensities that remained stable or resolved. DTI showed
      decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in
      bilateral cerebral WM and gray matter (GM) with no major change in NP status,
      medical symptoms, or medications over time. Lower FA was found in the following
      regions: left and right cerebral WM, and in GM areas including the
      parahippocampal gyrus, thalamus, precentral gyrus, postcentral gyrus, angular
      gyrus, parietal lobe, and cerebellum. Greater MD was found in the following
      regions: left and right cerebral WM, frontal cortex, left cerebral cortex, and
      the putamen. Conclusions This is the first longitudinal study of DTI and
      cognition in SLE, and results disclosed changes in both WM and GM without
      cognitive decline over an 18-month period. DTI abnormalities in our participants
      were not associated with emergent NP activity, medical decline, or medication
      changes, and the microstructural changes developed in the absence of
      macrostructural abnormalities on standard MRI. Microstructural changes may relate
      to ongoing inflammation, and the stability of cognitive function may be explained
      by medical treatment, the variability of NP progression in SLE, or the impact of
      cognitive reserve.

PMID- 30103650
TI  - Comparative genomics and evolution of trans-activating RNAs in Class 2 CRISPR-Cas
      systems.
AB  - Trans-activating CRISPR (tracr) RNA is a distinct RNA species that interacts with
      the CRISPR (cr) RNA to form the dual guide (g) RNA in type II and subtype V-B
      CRISPR-Cas systems. The tracrRNA-crRNA interaction is essential for pre-crRNA
      processing as well as target recognition and cleavage. The tracrRNA consists of
      an antirepeat, which forms an imperfect hybrid with the repeat in the crRNA, and
      a distal region containing a Rho-independent terminator. Exhaustive comparative
      analysis of the sequences and predicted structures of the Class 2 CRISPR guide
      RNAs shows that all these guide RNAs share distinct structural features, in
      particular, the nexus stem-loop that separates the repeat-antirepeat hybrid from
      the distal portion of the tracrRNA and the conserved GU pair at that end of the
      hybrid. These structural constraints might ensure full exposure of the spacer for
      target recognition. Reconstruction of tracrRNA evolution for 4 tight bacterial
      groups demonstrates random drift of repeat-antirepeat complementarity within a
      window of hybrid stability that is, apparently, maintained by selection. An
      evolutionary scenario is proposed whereby tracrRNAs evolved on multiple
      occasions, via rearrangement of a CRISPR array to form the antirepeat in
      different locations with respect to the array. A functional tracrRNA would form
      if, in the new location, the antirepeat is flanked by sequences that meet the
      minimal requirements for a promoter and a Rho-independent terminator.
      Alternatively, or additionally, the antirepeat sequence could be occasionally
      'reset' by recombination with a repeat, restoring the functionality of tracrRNAs
      that drift beyond the required minimal hybrid stability.

PMID- 30103649
TI  - Accuracy of Neck Ultrasonography in Predicting the Size and Location of
      Parathyroid Adenomas.
AB  - OBJECTIVES: Ultrasonography (US) is a reliable tool for the preoperative
      localization of parathyroid adenomas (PTAs). The aim of this study was to
      evaluate the accuracy of US for estimating both the size and the location of PTAs
      and the effect of operator expertise. STUDY DESIGN: Retrospective cohort study.
      SETTING: A single tertiary medical center. SUBJECTS AND METHODS: All patients who
      underwent parathyroidectomy for primary hyperparathyroidism between 1996 and 2012
      were included. The estimated PTA localization and size by preoperative ultrasound
      were compared with the intraoperative findings and pathology report. RESULTS: The
      cohort included 410 patients. US correctly localized the adenoma in 76% of cases
      with a sensitivity of 76.2% and a positive predictive value of 86.8%.
      Measurements were least accurate for adenomas measuring <1 cm in diameter (24%).
      Scans made by a single senior operator specializing in the neck had a higher
      accuracy rate than scans made by multiple operators, with a significant
      difference for small adenomas ( P < .001). CONCLUSIONS: US is an accurate and
      sensitive tool for evaluating PTA size and location. Neck US is less accurate for
      small adenomas (<1 cm). In these cases particularly, the experience and expertise
      of the US operator may play an important role.

PMID- 30103651
TI  - Worldwide distribution and abundance of microplastic: How dire is the situation?
AB  - The widespread occurrence of microplastic has invaded the environment to an
      extent that it appears to be present throughout the globe. This review
      investigated the global abundance and distribution of microplastics in marine and
      freshwater ecosystems. Furthermore, the issues and challenges have been addressed
      for better findings in microplastics studies. Findings revealed that the
      accumulation of microplastics varies geographically, with locations, hydrodynamic
      conditions, environmental pressure, and time. From this review, it is crucial
      that proper regulations are proposed and implemented in order to reduce the
      occurrence of microplastics in the aquatic environment. Without appropriate law
      and regulations, microplastic pollution will eventually threaten human
      livelihood.

PMID- 30103648
TI  - SopB activates the Akt-YAP pathway to promote Salmonella survival within B cells.
AB  - B cells are a target of Salmonella infection, allowing bacteria survival without
      inducing pyroptosis. This event is due to downregulation of Nlrc4 expression and
      lack of inflammasome complex activation, which impairs the secretion of IL-1beta.
      YAP phosphorylation is required for downregulation of Nlrc4 in B cells during
      Salmonella infection; however, the microorganism's mechanisms underlying the
      inhibition of the NLRC4 inflammasome in B cells are not fully understood. Our
      findings demonstrate that the Salmonella effector SopB triggers a signaling
      cascade involving PI3K, PDK1 and mTORC2 that activates Akt with consequent
      phosphorylation of YAP. When we deleted sopB in Salmonella, infected B cells that
      lack Rictor, or inhibited the signaling cascade using a pharmacological approach,
      we were able to restore the function of the NLRC4 inflammasome in B cells and the
      ability to control the infection. Furthermore, B cells from infected mice
      exhibited activation of Akt and YAP phosphorylation, suggesting that Salmonella
      also triggers this pathway in vivo. In summary, our data demonstrate that the
      Salmonella effector inositide phosphate phosphatase SopB triggers the PI3K-Akt
      YAP pathway to inhibit the NLRC4 inflammasome in B cells. This study provides
      further evidence that Salmonella triggers cellular mechanisms in B lymphocytes to
      manipulate the host environment by turning it into a survival niche to establish
      a successful infection.

PMID- 30103652
TI  - Environmental policies for drinks packaging in Georgia: A mini-review of EPR
      policies with a focus on incentive compatibility.
AB  - The paper investigates various approaches to an environmental policy regarding
      drinks containers in Georgia. Currently, most of the waste containers are
      landfilled or pollute the environment through littering, and separate collection
      and recycling of drinks containers are almost nonexistent. The Association
      Agreement with the EU, which entered into force in July 2016, stipulates the
      development of up-to-date waste management activities in this transition country.
      In accordance with the legal framework, this mini-review proposes an EPR policy
      for Georgia, based on the waste hierarchy. Various approaches for such an EPR
      policy are reviewed as regards their feasibility for a transition country, but in
      particular with regard to incentive compatibility: the policy should guide
      producers and consumers to comply with the regulations. Some cost estimates
      demonstrate the financial feasibility of the recommended solution. Practical
      experiences from Austria, Bulgaria, France and Germany provide a European
      context.

PMID- 30103653
TI  - Environmental profile of an innovative household biowaste dryer system based on
      Life Cycle Assessment.
AB  - An alternative approach to biowaste management involves the application of an
      innovative household dryer for the dehydration of biowaste at source, in order to
      significantly reduce its mass and volume, and subsequently the collection
      frequency. The main objective of this work is to assess the potential impacts of
      the system under examination, which involves the household dryer use and kerbside
      collection of the dehydrated residues (biomass), by conducting a Life Cycle
      Assessment study. The stages considered in the present study include the
      following: (a) the construction of the household biowaste dryer; (b) the use of
      the dryer and the collection of dehydrated residues; (c) the end-of-life
      treatment of the dryer. The results revealed that emissions coming from kerbside
      collection account for the vast majority of the total emissions from each
      category examined, apart from Terrestrial Ecotoxicity, where lignite, heavy fuel
      oil and diesel combustion during electricity production affect mainly this
      category. The potential impact in Global Warming over 100 years was estimated to
      be 8.87 kg CO2 eq / t biowaste. The Human Toxicity Potential was 1.86 kg 1,4-DB
      eq / t biowaste, Terrestrial Ecotoxicity Potential was 0.027 kg 1,4-DB eq / t
      biowaste, Freshwater Aquatic Ecotoxicity Potential was 0.0126 kg 1,4-DB eq / t
      biowaste and Marine Aquatic Ecotoxicity Potential was 521.85 kg 1,4-DB eq / t
      biowaste. Acidification Potential was estimated at 0.035 kg SO2 eq / t biowaste,
      while Eutrophication Potential was 0.0065 kg PO4- eq / t biowaste. Finally,
      Photochemical Oxidation Potential was 0.0014 kg C2H4 eq / t biowaste.

PMID- 30103654
TI  - Reference-Based Benefits for Colonoscopy and Arthroscopy: Large Differences in
      Patient Payments Across Procedures but Similar Behavioral Responses.
AB  - This study examines how reference-based benefits (RBB) affect patient out-of
      pocket payments across outpatient procedures. The California Public Employees'
      Retirement System (CalPERS) implemented RBB asymmetrically for outpatient
      procedures in 2012, only applying RBB to outpatient procedures performed in a
      hospital outpatient department (HOPD), and not applying RBB to outpatient
      procedures performed in a lower cost ambulatory surgery center. Using claims data
      (2009-2013) on arthroscopy and colonoscopy services, we found that for
      colonoscopy, CalPERS patients paid an average of 63.9% ( p < .01) more for HOPDs
      than ambulatory surgery centers in 2012. For arthroscopy, no statistically
      different cost sharing was found on average. However, high-priced HOPDs were
      17.3% and 17.9% less likely to be chosen by CalPERS patients in 2012 for
      colonoscopy and arthroscopy, respectively. These magnitudes increased in 2013 to
      25.2% and 24.2% less, respectively. Overall, responsiveness to RBB with regard to
      the most expensive HOPDs was similar despite varying cost sharing by procedure.

PMID- 30103655
TI  - Adolescents' and Parents' Attitudes Toward Adolescent Clinical Trial
      Participation: Changes Over One Year.
AB  - Little is known about how adolescents' and parents' thoughts about participation
      in clinical trials change over time. In this study, adolescent (14-17 years)
      parent dyads were asked about willingness to participate in a hypothetical
      reproductive health study. A year later, they were asked how their thoughts about
      the study had changed. Qualitative responses were coded and analyzed using
      framework analysis. Thirty-two percent of adolescents and 18% of parents reported
      changes in thoughts; reasons included general changes in perception, clearer
      understanding, new knowledge or experiences, increased maturity/age of
      adolescents, and changes in participants independent of the study. Adolescents
      and parents may benefit from learning about studies multiple times, and
      investigators should account for development and new experiences to optimize
      adolescent research enrollment.

PMID- 30103656
TI  - Concerning trends in allopathic medical school faculty rank for Indigenous
      people: 2014-2016.
AB  - BACKGROUND: Trends in faculty rank according to racial and ethnic composition
      have not been reviewed in over a decade. OBJECTIVE:  To study trends in faculty
      rank according to racial and ethnicity with a specific focus on Indigenous
      faculty, which has been understudied. METHODS: Data from the Association of
      American Medical Colleges' Faculty Administrative Management Online User System
      was used to study trends in race/ethnicity faculty composition and rank between
      2014 and 2016, which included information on 481,753 faculty members from 141 US
      allopathic medical schools. RESULTS: The majority of medical school faculty were
      White, 62.4% (n = 300,642). Asian composition represented 14.7% (n = 70,647).
      Hispanic, Latino, or of Spanish Origin; Multiple Race-Hispanic; Multiple Race-Non
      Hispanic; and Black/African American faculty represented 2.2%, 2.3%, 3.0%, and
      3.0%, respectively. Indigenous faculty members, defined as American Indian/Alaska
      Native (AIAN), Native Hawaiian or Other Pacific Islander (NHPI), represented the
      smallest percentage of faculty at 0.11% and 0.18%, respectively. White faculty
      predominated the full professor rank at 27.5% in 2016 with a slight decrease
      between 2014 and 2016. Indigenous faculty represented the lowest percent of full
      professor faculty at 5.2% in 2016 for AIAN faculty and a decline from 4.6% to
      1.6% between 2014 and 2016 for NHPI faculty (p < 0.001). CONCLUSIONS: While US
      medical school faculty are becoming more racially and ethnically diverse,
      representation of AIAN faculty is not improving and is decreasing significantly
      among NHPI faculty. Little progress has been made in eliminating health
      disparities among Indigenous people. Diversifying the medical workforce could
      better meet the needs of communities that historically and currently experience a
      disproportionate disease burden.

PMID- 30103657
TI  - A Grounded Theoretical Analysis of Room Elements Desired by Family Members and
      Visitors of Hospitalized Patients: Implications for Medical/Surgical Hospital
      Patient Room Design.
AB  - OBJECTIVE: To identify family members' and visitors' needs with relation to the
      design of a hospital room. BACKGROUND: There is a trend toward incorporating
      family zones in hospital patient rooms in order to improve patient satisfaction
      and encourage family caregivers to stay longer and overnight. METHOD: A mixed
      method study was employed. Interviews of patients and family caregivers were
      conducted to understand opportunities to improve hospital room designs based on
      recent experiences. Features intended to support short-term and overnight
      visitors were embedded in five full-scale simulated room design concepts. Small
      groups of family caregivers and patients toured two room design concepts and
      reacted real time to room features. A grounded theory approach was employed to
      identify emerging themes. RESULTS: A theoretical design framework is developed
      for the needs of family members and visitors for a range of time periods. This
      framework is founded upon desires to help make the patient feel more comfortable.
      There are various levels of helping the patient feel more comfortable, including
      visiting, keeping company, providing support, providing assistance, and being a
      caregiver. Beyond this core need, family members and visitors must take care of
      their own needs in order to feel comfortable in the hospital room. Activities
      associated with these needs include sitting, relaxing, eating, working, tending
      to daily needs, and resting overnight. CONCLUSIONS: Potential implications for
      architects, healthcare planners, and interior space designers are described.
      Design and renovation guidance for the hospital room environment in order to
      support the needs and expectations of families and visitors is provided.

PMID- 30103658
TI  - To establish a talent pool for global health in China: from political will to
      action.
AB  - Recently, China has played a more and more important role in global health,
      mainly by improving health outcomes of its own population nationwide and
      participating international health activities. In addition, China has
      participated in a dozen of international organizations, which all contained
      health domains, particularly the Belt and Road Initiative with an ambitious goal
      to improve health of the people in the countries alongside closely partnered with
      the World Health Organization. All these highlight the need of human resource for
      global health at the national level. The National Health and Family Planning
      Commission translated this political will into action - that a talent pool
      candidate for global health will be established in China. The establishment of
      the talent pool would be of great significance for China's engagement in global
      health activities. However, much work, such as training, collaboration, and
      innovation, etc., remains to be done in the future. Based on the successful
      practice, China can share lessons learned to other countries.

PMID- 30103659
TI  - Biomechanical study of optimum anchorage in dome-shaped high tibial osteotomy.
AB  - PURPOSE: There has been no report to date on any biomechanical study regarding
      the strength of fixation at the osteotomy site in dome-shaped high tibial
      osteotomy (HTO). In this study, we evaluated the biomechanical strength of a
      spacer that we improved and determined the medial site of HTO. METHODS: HTO
      correction angles of 15 degrees  and 20 degrees  were used in all experiments,
      which were performed on lower leg specimens from pigs ( n = 12). The osteotomy
      site was fixed by a locking plate and screws with a spacer. Compression (600
      N/min until 1100 N) and extended cyclic loading (200 cycles at 1000-2000 N) were
      performed to compare initial displacements in HTO specimens with and without
      spacers. RESULTS: The reduction ratios of displacement with and without spacers
      at HTO correction angles of 15 degrees  and 20 degrees  were 37% and 27%,
      respectively. No effect of the spacer at the correction angle of 15 degrees  was
      observed in the cyclic loading; however, the maximum displacement and amplitude
      were reduced with the spacer at the correction angle of 20 degrees . CONCLUSIONS
      AND CLINICAL RELEVANCE: When the HTO correction angle is small, the effect of the
      spacer is uncertain. However, the spacer is effective at an HTO correction angle
      of 20 degrees .

PMID- 30103661
TI  - A model-free test for detecting disease association signals with multiple genetic
      variants and covariates.
AB  - Discoveries and analyses of genetic variants at a gene or exome based on high
      throughput sequencing technology are increasingly feasible. Although many well
      known association tests have already been proposed in literature for testing
      whether a group of variants in a target region is associated with a disease of
      interest, however, the analytic challenges still remain profound. The power
      performance of these tests generally depends on the sample size, numbers of
      causal and neutral variants, variant frequency, effect size, and direction. Some
      of these factors are not easily controllable in practical applications. Further
      complications arise from missing genotype, population stratification or
      misspecification of the working model. Previous studies showed that many model
      based tests might create false positive results or decrease power when there was
      population stratification effect or missing genotype and simple imputation was
      used. Here, we demonstrate by simulations that type I errors of the well-known
      model-based tests are often inflated as well, even the working model deviates
      slightly from the true model. We propose a model-free test and show this test to
      be almost uniformly most powerful among the competing tests under very general
      simulation conditions with covariates. This test does not require genotype data
      to be complete and hence difficult imputation can be avoided. We also discuss how
      to adjust for the effect of population stratification based on principal
      components, and use a Shanghai Breast Cancer Study to demonstrate application of
      the new test.

PMID- 30103660
TI  - armDNA: A functional beta model for detecting age-related genomewide DNA
      methylation marks.
AB  - DNA methylation has been shown to play an important role in many complex
      diseases. The rapid development of high-throughput DNA methylation scan
      technologies provides great opportunities for genomewide DNA methylation-disease
      association studies. As methylation is a dynamic process involving time, it is
      quite plausible that age contributes to its variation to a large extent.
      Therefore, in analyzing genomewide DNA methylation data, it is important to
      identify age-related DNA methylation marks and delineate their functional
      relationship. This helps us to better understand the underlying biological
      mechanism and facilitate early diagnosis and prognosis analysis of complex
      diseases. We develop a functional beta model for analyzing DNA methylation data
      and detecting age-related DNA methylation marks on the whole genome by naturally
      taking sampling scheme into account and accommodating flexible age-methylation
      dynamics. We focus on DNA methylation data obtained through the widely used
      bisulfite conversion technique and propose to use a beta model to relate the DNA
      methylation level to the age. Adjusting for certain confounders, the functional
      age effect is left completely unspecified, offering great flexibility and
      allowing extra data dynamics. An efficient algorithm is developed for estimating
      unknown parameters, and the Wald test is used to detect age-related DNA
      methylation marks. Simulation studies and several real data applications were
      provided to demonstrate the performance of the proposed method.

PMID- 30103662
TI  - Modeling clustered binary data with excess zero clusters.
AB  - We establish a zero-inflated (random-effects) logistic-Gaussian model for
      clustered binary data in which members of clusters in one latent class have a
      zero response with probability one, and members of clusters in a second latent
      class yield correlated outcomes. Response probabilities in terms of random
      effects models are formulated, and maximum marginal likelihood estimation
      procedures based on Gaussian quadrature are developed. Application to esophageal
      cancer data in Chinese families is presented.

PMID- 30103663
TI  - Sample size calculations for group randomized trials with unequal group sizes
      through Monte Carlo simulations.
AB  - Group randomized trial design is common in cancer prevention and health promotion
      research with intervention development. Several methods have been developed to
      handle the design and analytical issues for group randomized trial including the
      intraclass correlation coefficient. The widely used methods for the sample size
      calculation for the group randomized trial assume equal sizes across groups. In
      practice this assumption often fails and group randomized trial studies suffer
      from considerably lower statistical power than as planned. A few studies have
      developed sample size calculation methods for unequal group sizes, but most of
      them are limited to continuous outcomes. In this study, we develop a method for
      sample size calculation for group randomized trial studies with unequal group
      sizes based on Monte Carlo simulation in the mixed effect model framework. This
      approach incorporates the variation of group sizes and can be applied to group
      randomized trials with different types of outcomes. Further, it is easy to
      implement and can be applied to most commonly used group randomized trial designs
      such as pre-and-post cross-sectional and cohort study designs. We demonstrate the
      application of the proposed approach to two-arm group randomized trial studies
      with continuous and binary outcomes through simulations and analysis of a real
      group randomized trial dataset.

PMID- 30103664
TI  - Late diagnosis of human immunodeficiency virus infections in high-risk groups in
      Karachi, Pakistan.
AB  - Human immunodeficiency virus (HIV) infection prevalence in Pakistan has been
      increasing in high-risk groups, including people who inject drugs (PWID) and
      transgender hijra sex workers (TG-HSWs) nationwide. Effective control of HIV
      requires early diagnosis of the infection. We investigated recency of HIV
      infections in newly-diagnosed cases in PWID and TG-HSWs. This was an
      observational study with convenience sampling. Overall, 210 HIV-positive subjects
      comprising an equal number of PWID and TG-HSWs were included. Antibody avidity
      was tested using the Maxim HIV-1 Limiting Antigen Avidity (LAg) EIA (Maxim
      Biomedical, Inc. Rockville, Maryland, USA). The mean age of study subjects was
      29.5 years: PWID, 28.5 years and TG-HSWs, 30.4 years. Study subjects were
      married, 27%, or unmarried. Eighteen percent of individuals had recently-acquired
      HIV infections: 19% of PWID and 17% of TG-HSWs. Eighty-two percent of individuals
      had long-term HIV infections: 81% of PWID and 83% of TG-HSWs. This is the first
      study identification of recent HIV-1 infections in Pakistan. We show that most
      newly-diagnosed HIV patients in the high-risk groups studied had long-term
      infections. There is an urgent need for intervention in these groups to
      facilitate early diagnosis and treatment of HIV infection to reduce transmission
      in Pakistan.

PMID- 30103665
TI  - Symptomatic gastric involvement in a parastomal hernia: uncommon presentation.
AB  - INTRODUCTION: A parastomal hernia (PSH) is the most common complication of a
      stoma creation. The PSH contents normally consist of mobile abdominal structures,
      i.e. omentum and small or large bowel loops. A herniated stomach is thereby very
      rare, given that only eight cases are reported in the literature. PATIENTS AND
      METHODS: Two female patients with clinical symptoms of gastric involvement in a
      PSH were admitted in our centre. RESULTS: Computed tomography (CT) imaging,
      nasogastric decompression and an efficient operative intervention ensured a good
      clinical outcome in both patients, but with a long hospital stay and temporary
      gastroparesis in one patient. Regarding our two cases and the eight cases
      reported in the literature, mainly older females with colostomies are at risk and
      most of them need surgery. CONCLUSIONS: In patients presenting with obstructive
      symptoms, one should be aware of a possible gastric outlet obstruction because of
      its involvement in a PSH, although sporadic. Surgery might be considered as the
      treatment of choice because conservative treatment mostly fails. Earlier surgery
      might perhaps also reduce postoperative hospital stay and gastroparesis.

PMID- 30103666
TI  - Infantile Myofibromatosis With Intracranial Extradural Involvement and PDGFRB
      Mutation: A Case Report and Review of the Literature.
AB  - Infantile myofibroma is a rare benign mesenchymal tumor that presents as solitary
      or multiple lesions (myofibromatosis) in the skin, soft tissue, bone, or internal
      organs. It most commonly affects the head and neck of infants and young children,
      but it can also affect adults. Intracranial involvement is reported to be
      extremely rare, and its clinical picture has been poorly characterized. Recently,
      it has been demonstrated that germline and somatic mutations in the platelet
      derived growth factor receptor beta (PDGFRB) are associated with familial
      infantile myofibromatosis. We report a case of infantile myofibromatosis with
      predominant posterior fossa extradural involvement in a 14-year-old adolescent
      girl with a confirmed mutation in the PDGFRB gene.

PMID- 30103667
TI  - Arteriogenic Thoracic Outlet Syndrome Presenting as Cervical Radiculopathy.
AB  - Thoracic outlet syndrome (TOS) is an infrequent entity encountered by medical
      practitioners attributed to compression of the neurovascular structures passing
      through the thoracic outlet. Here, we report the presentation of a young adult
      who was referred for workup of cervical radiculopathy and was planned to undergo
      an anterior cervical discectomy and fusion. A dynamic cerebral angiogram was
      performed and confirmed the diagnosis of arteriogenic TOS. The etiology,
      presentation, and diagnostic workup of TOS are briefly discussed with emphasis
      placed on maintaining a healthy suspicion in order to differentiate from cervical
      radiculopathy, make an accurate diagnosis, and avoid inappropriate surgery.

PMID- 30103668
TI  - Visceral oxidative stress during antegrade cerebral perfusion and lower body
      circulatory arrest.
AB  - BACKGROUND: Antegrade cerebral perfusion (ACP) is the standard neuroprotection
      method in aortic surgery. Visceral ischemia during this modality brings out some
      controversies. We aimed to investigate the level of oxidative stress at the lower
      part of body during ACP. METHODS: Thirty consecutive patients underwent elective
      ascending aorta and hemiarch repair with ACP (without distal perfusion) were
      enrolled to study. The patients were enrolled into two groups which were based on
      50th percentile of ACP duration (15 patients in each group). Blood samples from
      inferior vena cava at the end of ACP were collected to assess oxidative stress
      with biochemical parameters such as lactate, advanced oxidative protein products
      (AOPP) and thiol levels. Clinical follow-up parameters regarding to visceral and
      spinal cord ischemia were recorded. There were no clinical complications at both
      groups. RESULTS: Mean ACP duration for the study group was found to be 15 min (10
      28 min). Lactate, AOPP, and thiol levels were found to be similar between two
      groups. Furthermore, correlation analysis revealed only low level of correlation
      between ACP duration and lactate levels. Renal and liver function tests were
      found to be similar between groups. CONCLUSIONS: Immediate parameters (such as
      lactate, AOPP, and thiol) that show alterations in response to oxidative stress
      were not affected by the duration of ACP. Therefore, ACP without distal perfusion
      may not be harmful when conducted for short duration.

PMID- 30103671
TI  - Bifunctionally engineered polyethylenimines as efficient DNA carriers and
      antibacterials against resistant pathogens.
AB  - In this study, we have designed and developed two series of bifunctional
      conjugates by tethering polyethylenimine with streptomycin. By varying the amount
      of streptomycin, conjugates, polyethylenimine-streptomycin, have been synthesized
      and characterized spectroscopically. Gel electrophoresis assay revealed a slight
      decrease in the cationic charge density on the conjugates as these retarded the
      mobility of pDNA at higher w/w ratios. Further, transfection studies showed that
      both the series of conjugates transfected the mammalian cells efficiently with
      low-molecular weight polyethylenimine-streptomycin conjugates were more competent
      (~9-fold enhancement with respect to native bPEI) exhibiting high cell viability
      too. Besides, both the series of conjugates displayed excellent antibacterial
      activity on pathogenic bacteria, even better than native streptomycin on
      resistant strains. Altogether, these results ensure the promising potential of
      the projected bifunctional conjugates as safe and efficient gene delivery vectors
      as well as antibacterials for future biomedical applications.

PMID- 30103670
TI  - Autosomal dominant retinitis pigmentosa-associated gene PRPF8 is essential for
      hypoxia-induced mitophagy through regulating ULK1 mRNA splicing.
AB  - Aged and damaged mitochondria can be selectively degraded by specific autophagic
      elimination, termed mitophagy. Defects in mitophagy have been increasingly linked
      to several diseases including neurodegenerative diseases, metabolic diseases and
      other aging-related diseases. However, the molecular mechanisms of mitophagy are
      not fully understood. Here, we identify PRPF8 (pre-mRNA processing factor 8), a
      core component of the spliceosome, as an essential mediator in hypoxia-induced
      mitophagy from an RNAi screen based on a fluorescent mitophagy reporter, mt
      Keima. Knockdown of PRPF8 significantly impairs mitophagosome formation and
      subsequent mitochondrial clearance through the aberrant mRNA splicing of ULK1,
      which mediates macroautophagy/autophagy initiation. Importantly, autosomal
      dominant retinitis pigmentosa (adRP)-associated PRPF8 mutant R2310K is defective
      in regulating mitophagy. Moreover, knockdown of other adRP-associated splicing
      factors, including PRPF6, PRPF31 and SNRNP200, also lead to ULK1 mRNA mis
      splicing and mitophagy defects. Thus, these findings demonstrate that PRPF8 is
      essential for mitophagy and suggest that dysregulation of spliceosome-mediated
      mitophagy may contribute to pathogenesis of retinitis pigmentosa.

PMID- 30103672
TI  - Cross-sectional study of prevalence of dementia, behavioural symptoms, mobility,
      pain and other health parameters in nursing homes in Austria and the Czech
      Republic: results from the DEMDATA project.
AB  - BACKGROUND: This paper provides a first comparative exploratory analysis of our
      findings from DEMDATA, a collaborative project between Austria and the Czech
      Republic. Analysed here are data from the residents and the environment
      assessment protocol. METHODS: In a cross sectional study design, residents from
      randomly drawn and stratified nursing homes were investigated using a common
      study protocol. RESULTS: From a total resident pool of 1666 persons, 1085 (571 in
      Austria, 514 in the Czech Republic) persons signed a consent form and
      participated in the data collection. More than 70% of residents assessed were
      female and the population was on average 85 years old. A discrepancy between the
      presence of a medical diagnosis in the charts of the residents and the results of
      cognitive testing was found. In Austria, 85.2%, in the Czech Republic 53.0% of
      residents had cognitive impairment. In Austria 80.0%, and in the Czech Republic
      56.7% had behavioural problems. With respect to pain, 44.8% in Austria, and 51.5%
      in the Czech Republic had mild to severe pain. 78.4% of Austrian and 74.5% of the
      residents had problems with mobility and both populations were in danger of
      malnutrition. CONCLUSIONS: Most of the prevalence rates are comparable with
      previous studies also using direct resident assessment. Variations in prevalence
      rates seem to result mainly from the assessment technique (direct cognitive
      testing vs. medical chart review). The high prevalence rates for dementia,
      behavioural symptoms, pain and malnutrition indicate an immediate call for
      attention to further research and practice development.

PMID- 30103673
TI  - Identification and characterization of ncRNA-associated ceRNA networks in
      Arabidopsis leaf development.
AB  - BACKGROUND: Leaf development is a complex biological process that is accompanied
      by wide transcriptional changes. Many protein-coding genes have been
      characterized in plant leaves, but little attention has been given to noncoding
      RNAs (ncRNAs). Moreover, increasing evidence indicates that an intricate
      interplay among RNA species, including protein-coding RNAs and ncRNAs, exists in
      eukaryotic transcriptomes, however, it remains elusive in plant leaves. RESULTS:
      We detected novel ncRNAs, such as circular RNAs (circRNAs) and long noncoding
      RNAs (lncRNAs), and further constructed and analyzed their associated competitive
      endogenous RNA (ceRNA) networks in Arabidopsis leaves. Transcriptome profiling
      showed extensive changes during leaf development. In addition, comprehensive
      detection of circRNAs in other plant leaves suggested that circRNAs are
      widespread in plant leaves. To investigate the complex post-transcriptional
      interactions in Arabidopsis leaves, we constructed a global circRNA/lncRNA
      associated ceRNA network. Functional analysis revealed that ceRNAs were highly
      correlated with leaf development. These ceRNAs could be divided into six
      clusters, which were enriched for different functional classes. Stage-specific
      ceRNA networks were further constructed and comparative analysis revealed
      different roles of stage common and specific hub ceRNAs. CONCLUSIONS: Our results
      demonstrate that understanding the ceRNA interactions will lead insights into
      gene regulations implicated in leaf development.

PMID- 30103674
TI  - Transcriptome and DNA methylome reveal insights into yield heterosis in the curds
      of broccoli (Brassica oleracea L var. italic).
AB  - BACKGROUND: Curds are the main edible organs, which exhibit remarkable yield
      heterosis in F1 hybrid broccoli. However, the molecular basis underlying
      heterosis in broccoli remains elusive. RESULTS: In the present study,
      transcriptome profiles revealed that the hybridization made most genes show
      additive expression patterns in hybrid broccoli. The differentially expressed
      genes including the non-additively expressed genes detected in the hybrid
      broccoli and its parents were mainly involved in light, hormone and hydrogen
      peroxide-mediated signaling pathways, responses to stresses, and regulation of
      floral development, which suggested that these biological processes should play
      crucial roles in the yield heterosis of broccoli. Among them, light and hydrogen
      peroxide-mediated signaling pathways represent two novel classes of regulatory
      processes that could function in yield or biomass heterosis of plants. Totally,
      53 candidate genes closely involved in curd yield heterosis were identified.
      Methylome data indicated that the DNA methylation ratio of the hybrids was higher
      than that of their parents. However, the DNA methylation levels of most sites
      also displayed additive expression patterns. These sites with differential
      methylation levels were predominant in the intergenic regions. In most cases, the
      changes of DNA methylation levels in gene regions did not significantly affect
      their expression levels. CONCLUSIONS: The differentially expressed genes, the
      regulatory processes and the possible roles of DNA methylation modification in
      the formation of curd yield heterotic trait were discovered. These findings
      provided comprehensive insights into the curd yield heterosis in broccoli, and
      were significant for breeding high-yield broccoli varieties.

PMID- 30103676
TI  - Catheter ablation for treatment of patients with atrial fibrillation and heart
      failure: a meta-analysis of randomized controlled trials.
AB  - BACKGROUND: There is a little evidence for the effects of catheter ablation (CA)
      on hard endpoints in patients with atrial fibrillation (AF) and heart failure
      (HF). METHODS: PubMed, Embase and Cochrane Library were searched for randomized
      controlled trials (RCTs) enrolling patients with AF and HF who were assigned to
      CA, rate control or medical rhythm control groups. This meta-analysis was
      performed by using random-effect models. RESULTS: Seven RCTs enrolling 856
      participants were included in this meta-analysis. CA reduced the risks of all
      cause mortality (risk ratio [RR] 0.52, 95% CI 0.35 to 0.76), HF readmission (RR
      0.58, 95% CI 0.46 to 0.66) and the composite of all-cause mortality and HF
      readmission (RR 0.55, 95% CI 0.47 to 0.66) when compared with control. But there
      was no significant difference in cerebrovascular accident (RR 0.56, 95% CI 0.23
      to 1.36) between two groups. Compared with control, CA was associated with
      improvement in left ventricular ejection fraction (mean difference [MD] 7.57, 95%
      CI 3.72 to 11.41), left ventricular end systolic volume (MD -14.51, 95% CI -26.84
      to - 2.07), and left ventricular end diastolic volume (MD -3.78, 95% CI -18.51 to
      10.96). Patients undergoing CA exhibited increased peak oxygen consumption (MD
      3.16, 95% CI 1.09 to 5.23), longer 6-min walk test distance (MD 26.67, 95% CI
      12.07 to 41.27), and reduced Minnesota Living with Heart Failure Questionnaire
      scores (MD -9.49, 95% CI -14.64 to - 4.34) than those in control group. Compared
      with control, CA was associated with improved New York Heart Association class
      (MD -0.74, 95% CI -0.83 to - 0.64) and lower B-type natriuretic peptide levels
      (MD -105.96, 95% CI -230.56 to 19.64). CONCLUSIONS: CA was associated with
      improved survival, morphologic changes, functional capacity and quality of life
      relative to control. CA should be considered in patients with AF and HF.

PMID- 30103675
TI  - Horizontal gene transfer plays a major role in the pathological convergence of
      Xanthomonas lineages on common bean.
AB  - BACKGROUND: Host specialization is a hallmark of numerous plant pathogens
      including bacteria, fungi, oomycetes and viruses. Yet, the molecular and
      evolutionary bases of host specificity are poorly understood. In some cases,
      pathological convergence is observed for individuals belonging to distant
      phylogenetic clades. This is the case for Xanthomonas strains responsible for
      common bacterial blight of bean, spread across four genetic lineages. All the
      strains from these four lineages converged for pathogenicity on common bean,
      implying possible gene convergences and/or sharing of a common arsenal of genes
      conferring the ability to infect common bean. RESULTS: To search for genes
      involved in common bean specificity, we used a combination of whole-genome
      analyses without a priori, including a genome scan based on k-mer search.
      Analysis of 72 genomes from a collection of Xanthomonas pathovars unveiled 115
      genes bearing DNA sequences specific to strains responsible for common bacterial
      blight, including 20 genes located on a plasmid. Of these 115 genes, 88 were
      involved in successive events of horizontal gene transfers among the four genetic
      lineages, and 44 contained nonsynonymous polymorphisms unique to the causal
      agents of common bacterial blight. CONCLUSIONS: Our study revealed that host
      specificity of common bacterial blight agents is associated with a combination of
      horizontal transfers of genes, and highlights the role of plasmids in these
      horizontal transfers.

PMID- 30103677
TI  - Assessment of barriers and facilitators in the implementation of appropriate use
      criteria for elective percutaneous coronary interventions: a qualitative study.
AB  - BACKGROUND: The use of inappropriate elective Percutaneous Coronary Intervention
      (PCI) has decreased over time, but hospital-level variation in the use of
      inappropriate PCI persists. Understanding the barriers and facilitators to the
      implementation of Appropriate Use Criteria (AUC) guidelines may inform efforts to
      improve elective PCI appropriateness. METHODS: All hospitals performing PCI in
      Washington State were categorized by their use of inappropriate elective PCI in
      2010 to 2013. Semi-structured, qualitative telephone interviews were then
      conducted with 17 individual interviews at 13 sites in Washington State to
      identify barriers and facilitators to the implementation of the AUC guidelines.
      An inductive and deductive, team-based analytical approach, drawing primarily on
      Matrix analysis was performed to identify factors affecting implementation of the
      AUC. RESULTS: Specific facilitators were identified that supported successful
      implementation of the AUC. These included collaborative catheterization
      laboratory environments that allow all staff to participate with questions and
      opinions; ongoing AUC education with catheterization laboratory teams and
      referring providers; internal AUC peer review processes; interventional
      cardiologist be directly involved with the pre-procedural review process;
      checklist-based algorithms for pre-procedural documentation; systems redesign to
      include insurance companies; and AUC educational information with patients.
      Barriers to implementation of the AUC included external pressures, such as
      competition for patients, and the lack of shared medical records with sites that
      referred patients for coronary angiography. CONCLUSIONS: The identified
      facilitators enabled sites to successfully implement the AUC. Catheterization
      laboratories struggling to successfully implement the AUC may consider utilizing
      these strategies to improve their processes to improve patient selection for
      elective PCI.

PMID- 30103678
TI  - Incidental finding of cardiac hydatid cysts, report of two cases.
AB  - BACKGROUND: Hydatid is a parasitic infection which can affect any organ of body.
      In some organs like liver and lung; it can be found regularly while in other
      organs like heart, it is seen very rarely. Cardiac hydatid cysts comprise less
      than of 2% of hydatid infection cases and may be detected incidentally. CASE
      PRESENTATION: Authors report two cases of cardiac hydatid cysts in young adult
      patients living in rural areas of the country with positive animal contact. Both
      patients were complained from shortness of breath and cough. Contrast enhanced
      chest computed tomography (CT) revealed left ventricular wall hydatid cysts in
      addition to lung and liver hydatid cysts. CONCLUSION: Cardiac hydatid cyst is a
      rare finding with wide range of signs and symptoms. These may be suspected in
      patients coming from endemic areas. Echocardiographic follow up of patients with
      liver or lung hydatid cysts can be helpful.

PMID- 30103679
TI  - Evaluation of the effects of dexmedetomidine infusion on oxygenation and lung
      mechanics in morbidly obese patients with restrictive lung disease.
AB  - BACKGROUND: Dexmedetomidine infusion improves oxygenation and lung mechanics in
      patients with chronic obstructive lung disease; however, its effect in patients
      with restrictive lung disease has not been thoroughly investigated yet. The aim
      of this work was to evaluate the effects of dexmedetomidine infusion on
      oxygenation and lung mechanics in morbidly obese patients with restrictive lung
      disease. METHODS: Forty-two morbidly obese patients scheduled for bariatric
      surgery were included in the study. Patients were randomized to receive either
      dexmedetomidine infusion at a bolus dose of 1mcg/Kg followed by infusion at 1
      mcg/Kg/hour for 90 min (Dexmedetomidine group), or normal saline infusion
      (Control group). Both groups were compared with regard to: oxygenation {P/F
      ratio: PaO2/fraction of inspired oxygen (FiO2)}, lung compliance, dead space,
      plateau pressure, blood pressure, and heart rate. RESULTS: Dexmedetomidine group
      showed significant improvement of the PaO2/FiO2 ratio, and higher lung compliance
      compared to control group by the end of drug infusion. Dexmedetomidine group
      demonstrated decreased dead space, plateau pressure, blood pressure, and heart
      rate compared to control group by the end of drug infusion. CONCLUSION: A 90-min
      dexmedetomidine infusion resulted in moderate improvement in oxygenation and lung
      mechanics in morbidly obese patients with restrictive lung disease. TRIAL
      REGISTRATION: clinicaltrials.gov : NCT02843698 on 20 July 2016.

PMID- 30103680
TI  - Mesenchymal stem cell transplantation improves chronic colitis-associated
      complications through inhibiting the activity of toll-like receptor-4 in mice.
AB  - BACKGROUND: A variety of extra-intestinal manifestations (EIMs), including
      hepatobiliary complications, are associated with inflammatory bowel disease
      (IBD). Mesenchymal stem cells (MSCs) have been shown to play a potential role in
      the therapy of IBD. This study was designed to investigate the effect and
      mechanism of MSCs on chronic colitis-associated hepatobiliary complications using
      mouse chronic colitis models induced by dextran sulfate sodium (DSS). METHODS:
      DSS-induced mouse chronic colitis models were established and treated with MSCs.
      Severity of colitis was evaluated by disease activity index (DAI), body weight
      (BW), colon length and histopathology. Serum lipopolysaccharide (LPS) levels were
      detected by limulus amebocyte lysate test (LAL-test). Histology and liver
      function of the mice were checked correspondingly. Serum LPS levels and bacterial
      translocation of mesenteric lymph nodes (MLN) were detected. Pro-inflammatory
      cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon-gamma
      (IFN-gamma), interleukin-1beta (IL-1beta), interleukin-17A (IL-17A), Toll
      receptor 4 (TLR4), TNF receptor-associated factor 6 (TRAF6) and nuclear factor
      kappa B (NF-kappaB) were detected by immunohistochemical staining, western blot
      analysis and real-time PCR, respectively. RESULTS: The DSS-induced chronic
      colitis model was characterized by reduced BW, high DAI, worsened histologic
      inflammation, and high levels of LPS and E. coli. Liver histopathological
      lesions, impaired liver function, enhanced proteins and mRNA levels of TNF-alpha,
      IFN-gamma, IL-1beta, IL-17A, TLR4, TRAF6 and NF-kappaB were observed after DSS
      administration. MSCs transplantation markedly ameliorated the pathology of colon
      and liver by reduction of LPS levels and proteins and mRNA expressions of TNF
      alpha, IFN-gamma, IL-1beta, IL-17A, TLR4, TRAF6 and NF-kappaB. CONCLUSIONS: MSCs
      can improve chronic colitis-associated hepatobiliary complications, probably by
      inhibition of enterogenous endotoxemia and hepatic inflammation through LPS/TLR4
      pathway. MSCs may represent a novel therapeutic approach for chronic colitis
      associated hepatobiliary complications.

PMID- 30103681
TI  - Preliminary evidence for an increased likelihood of a stable trajectory in mild
      cognitive impairment in individuals with higher motivational abilities.
AB  - BACKGROUND: Motivational abilities (MA), that describe skills in relation to goal
      oriented behavior, have recently been found to be associated with
      neuropathological aging. Here we examine the impact of MA on the long-term course
      of mild cognitive impairment (MCI). METHODS: We followed-up N = 64 individuals
      diagnosed with MCI (Mage = 73 years, 44% female) for 3 years. MA were assessed by
      long-term informants of the participants using two scales: motivation and
      decision regulation [Volitional Components Questionnaires, VCQ, (Kuhl and
      Fuhrmann, Decomposing self-regulation and self-control: the volitional components
      inventory, 1998)]. Cognitive abilities were assessed with the Mini Mental State
      Examination (J Psychiatr Res 12:189-98, 1975). Survival analyses and multilevel
      modeling (MLM) were applied to determine the predicting effect of informant-rated
      MA at baseline on the likelihood of MCI stability and on the trajectory of
      cognitive abilities. RESULTS: Fifty percent (n = 32) of the MCI participants
      remained stable, while 32.8% (n = 21) and 17.2% (n = 11) converted to Alzheimer's
      disease (AD) or dropped-out, respectively. Survival analyses revealed that MCI
      cases with higher-rated MA at baseline were more likely to exert a stable course
      in MCI over 3 years (p = 0.036) when controlling for demographic characteristics
      and executive function. MLM analyses indicated that higher informant-rated MA at
      baseline were significantly related to higher cognitive abilities, even when
      controlling for MCI subtype (p = 0.030). CONCLUSIONS: This study provides
      preliminary longitudinal evidence for a lower risk of conversion to AD and higher
      cognitive abilities by higher rated MA at an early stage of MCI.

PMID- 30103683
TI  - A barcode of multilocus nuclear DNA identifies genetic relatedness in pre- and
      post-Artemether/Lumefantrine treated Plasmodium falciparum in Nigeria.
AB  - BACKGROUND: The decline in the efficacy of artemisinin-based combination
      treatment (ACT) in some endemic regions threatens the progress towards global
      elimination of malaria. Molecular surveillance of drug resistance in malaria
      endemic regions is vital to detect the emergence and spread of mutant strains.
      METHODS: We observed 89 malaria patients for the efficacy of artemether
      lumefantrine for the treatment of uncomplicated Plasmodium falciparum infections
      in Lagos, Nigeria and determined the prevalence of drug resistant strains in the
      population. Parasite clearance rates were determined by microscopy and the highly
      sensitive var gene acidic terminal sequence (varATS) polymerase chain reaction
      for 65 patients with samples on days 0, 1, 3, 7, 14, 21 and 28 after commencement
      of treatment. The genomic finger print of parasite DNA from pre- and post
      treatment samples were determined using 24 nuclear single nucleotide
      polymorphisms (SNP) barcode for P. falciparum. Drug resistance associated alleles
      in chloroquine resistance transporter gene (crt-76), multidrug resistance genes
      (mdr1-86 and mdr1-184), dihydropteroate synthase (dhps-540), dihydrofolate
      reductase (dhfr-108) and kelch domain (K-13580) were genotyped by high resolution
      melt analysis of polymerase chain reaction (PCR) fragments. RESULTS: By varATS
      qPCR, 12 (18.5%) of the participants had detectable parasite DNA in their blood
      three days after treatment, while eight (12.3%) individuals presented with
      genotypable day 28 parasitaemia. Complexity of infection (CoI) was 1.30 on day 0
      and 1.34 on day 28, the mean expected heterozygosity (HE) values across all
      barcodes were 0.50 +/- 0.05 and 0.56 +/- 0.05 on days 0 and 28 respectively.
      Barcode (pi) pairwise comparisons showed high genetic relatedness of day 0 and
      day 28 parasite isolates in three (37.5%) of the eight individuals who presented
      with re-appearing infections. Crt-76 mutant allele was present in 38 (58.5%)
      isolates. The mdr1-86 mutant allele was found in 56 (86.2%) isolates. No mutation
      in the K-13580 was observed. CONCLUSIONS: Persistence of DNA-detectable
      parasitaemia in more than 18% of cases after treatment and indications of genetic
      relatedness between pre- and post-treatment infections warrants further
      investigation of a larger population for signs of reduced ACT efficacy in
      Nigeria.

PMID- 30103682
TI  - Amelioration of spinal cord injury in rats by blocking peroxynitrite/calpain
      activity.
AB  - BACKGROUND: Spinal cord injury (SCI) is one of the leading causes of disability
      and chronic pain. In SCI-induced pathology, homeostasis of the nitric oxide (NO)
      metabolome is lost. Major NO metabolites such as S-nitrosoglutathione (GSNO) and
      peroxynitrite are reported to play pivotal roles in regulating the activities of
      key cysteine proteases, calpains. While peroxynitrite (a metabolite of NO and
      superoxide) up regulates the activities of calpains leading to neurodegeneration,
      GSNO (a metabolite of NO and glutathione) down regulates the activities of
      calpains leading to neuroprotection. In this study, effect of GSNO on locomotor
      function and pain threshold and their relationship with the levels of
      peroxynitrite and the activity of calpain in the injured spinal cord were
      investigated using a 2-week rat model of contusion SCI. RESULTS: SCI animals were
      initially treated with GSNO at 2 h after the injury followed by a once daily dose
      of GSNO for 14 days. Locomotor function was evaluated by "Basso Beattie and
      Bresnahan (BBB) locomotor rating scale" and pain by mechanical allodynia.
      Peroxynitrite level, as expression of 3-nitrotyrosine (3-NT), calpain activity,
      as the degradation products of calpain substrate alpha II spectrin, and nNOS
      activity, as the expression phospho nNOS, were measured by western blot analysis.
      Treatment with GSNO improved locomotor function and mitigated pain. The treatment
      also reduced the levels of peroxynitrite (3-NT) and decreased activity of
      calpains. Reduced levels of peroxynitrite resulted from the GSNO-mediated
      inhibition of aberrant activity of neuronal nitric oxide synthase (nNOS).
      CONCLUSIONS: The data indicates that higher levels of 3-NT and aberrant
      activities of nNOS and calpains correlated with SCI pathology and functional
      deficits. Treatment with GSNO improved locomotor function and mitigated
      mechanical allodynia acutely post-injury. Because GSNO shows potential to
      ameliorate experimental SCI, we discuss implications for GSNO therapy in clinical
      SCI research.

PMID- 30103684
TI  - Safety and efficacy of Rapamune(r) (Sirolimus) in kidney transplant recipients:
      results of a prospective post-marketing surveillance study in Korea.
AB  - BACKGROUND: Few post-marketing surveillance studies have examined the safety and
      efficacy of Rapamune(r) (Sirolimus) in Asian countries. This study aimed to
      better understand safety and efficacy of Rapamune for kidney transplant
      recipients in the routine clinical practice setting in Korea. METHODS: This was
      an open-label, non-comparative, observational, prospective, multi-center, post
      marketing surveillance study conducted at 15 Korean transplant centers between 31
      August 2009 and 24 September 2015. The subjects were administered Rapamune as
      part of routine practice. The safety was monitored based on reporting of adverse
      events (AEs). Efficacy endpoints included acute rejection, graft function, graft
      survival, and patient survival. RESULTS: Rapamune was most commonly used for late
      conversion therapy after post-transplant 1 year and was substituted for anti
      metabolites (63.6%) or calcineurin inhibitors (28.7%). The median treatment
      duration of Rapamune was 182 days. Among 209 subjects enrolled, AEs and adverse
      drug reactions (ADRs) were reported in 54.07% and 43.06% of subjects,
      respectively, in the safety analysis set. Most of the AEs were expected (96.21%),
      mild (75.83%), did not result in any action taken with regard to the study drug
      (72.99%), and resolved by the end of the study (75.36%). The most frequently
      reported AEs/ADRs were pharyngitis and diarrhea. Most of the serious AEs/ADRs
      occurred in one or two subjects. Unexpected ADRs of renal artery occlusion and
      cholangitis were reported by one subject each. The incidence of biopsy-proven
      acute rejection was 2.87%. At the end of the study, 99.51% of the subjects and
      their grafts had survived. The mean eGFR was 64.72 +/- 19.56 mL/min. CONCLUSIONS:
      Rapamune had an acceptable safety profile in prevention of kidney allograft
      rejection in Korea.

PMID- 30103685
TI  - Ultrasound cardiography examinations detect victims' long-term realized and
      potential consequences after major disasters: a case-control study.
AB  - BACKGROUND: An increase in cardiovascular diseases has been reported following
      major disasters. Previous work has shown that ultrasonographic findings from
      ultrasound cardiography examination (UCG) increased until the 44th month after
      the tsunami caused by the Great East Japan Earthquake. The present study
      conducted UCG among victims in the tsunami disaster area and investigated the
      frequency of disaster-related cardiovascular diseases and changes over time until
      the 55th month after the disaster. METHODS: The subjects were residents of
      temporary housing complexes and neighboring housing in Watari-gun, Miyagi
      Prefecture, Japan. There were 207 subjects in the 18th month, 125 in the 30th
      month, 121 in the 44th month, and 106 in the 55th month after the disaster. Data
      were collected through UCG and self-report questionnaire. RESULTS: Significant
      changes were observed among subjects with clinical findings from the UCG, which
      increased over the study period-from 42.0 to 60.8, 72.7, and 73.6% beginning in
      the 18th month after the disaster (p < 0.0001). CONCLUSIONS: It is possible that
      the UCG can become a useful examination to visualize the potential impact of a
      major disaster on the cardiac function of victims. Victims with clinical findings
      continued increasing not only during the acute phase after a disaster but also in
      the long term. We therefore need to keep this in mind, and note that it is
      important to establish a support system to control cardiovascular diseases from
      the early stage of disaster. TRIAL REGISTRATION: UMIN; ID000029802. R000034050 .
      2 November 2017.

PMID- 30103686
TI  - Validation of a simplex PCR assay enabling reliable identification of clinically
      relevant Candida species.
AB  - BACKGROUND: Fungal bloodstream infections (BSI) may be serious and are associated
      with drastic rise in mortality and health care costs. Candida spp. are the
      predominant etiological agent of fungal sepsis. The prompt and species-level
      identification of Candida may influence patient outcome and survival. The aim of
      this study was to develop and evaluate the CanTub-simplex PCR assay coupled with
      Tm calling and subsequent high resolution melting (HRM) analysis to barcode seven
      clinically relevant Candida species. METHODS: Efficiency, coefficient of
      correlation and the limit of reliable detection were estimated on purified
      Candida EDTA-whole blood (WB) reference panels seeded with Candida albicans,
      Candida glabrata, Candida parapsilosis, Candida tropicalis, Candida krusei,
      Candida guilliermondii, Candida dubliniensis cells in a 6-log range.
      Discriminatory power was measured on EDTA-WB clinical panels on three different
      PCR platforms; LightCycler(r)96, LightCycler(r) Nano, LightCycler(r) 2.0. Inter-
      and intra assay consistencies were also calculated. RESULTS: The limit of
      reliable detection proved to be 0.2-2 genomic equivalent and the method was
      reliable on broad concentration ranges (106-10 CFU) providing distinctive melting
      peaks and characteristic HRM curves. The diagnostic accuracy of the
      discrimination proved to be the best on Roche LightCycler(r)2.0 platform.
      Repeatability was tested and proved to be % C.V.: 0.14 +/- 0.06 on reference- and
      % C.V.: 0.14 +/- 0.02 on clinical-plates accounting for a very high accuracy.
      Reproducibility was % C.V.: 0.11 between reference- and % C.V.: 0.12between
      clinical-panels which is highly acceptable. CONCLUSION: Our assay demonstrates
      recent advances on Tm calling and HRM analysis for the molecular identification
      of relevant Candida species. This unique, simplex PCR assay may be capable to
      outperform conventional phenotypic methods by reducing time and providing
      accurate and reliable results directly from blood (2 h) or from whole blood
      culture bottles (12-24 h).

PMID- 30103688
TI  - Continuity and utilization of health and community care in elderly patients with
      heart failure before and after hospitalization.
AB  - BACKGROUND: The period after hospitalization due to deteriorated heart failure
      (HF) is characterized as a time of high generalized risk. The transition from
      hospital to home is often problematic due to insufficient coordination of care,
      leading to a fragmentation of care rather than a seamless continuum of care. The
      aim was to describe health and community care utilization prior to and 30 days
      after hospitalization, and the continuity of care in patients hospitalized due to
      de novo or deteriorated HF from the patients' perspective and from a medical
      chart review. METHODS: This was a cross-sectional study with consecutive
      inclusion of patients hospitalized at a county hospital in Sweden due to
      deteriorated HF during 2014. Data were collected by structured telephone
      interviews and medical chart review and analyzed with the Spearman's rank
      correlation coefficient and Chi square. A P value of 0.05 was considered
      significant. RESULTS: A total of 121 patients were included in the study, mean
      age 82.5 (+/-6.8) and 49% were women. Half of the patients had not visited any
      health care facility during the month prior to the index hospital admission, and
      79% of the patients visited the emergency room (ER) without a referral. Among
      these elderly patients, a total of 40% received assistance at home prior to
      hospitalization and 52% after discharge. A total of 86% received written
      discharge information, one third felt insecure after hospitalization and lacked
      knowledge of which health care provider to consult with and contact in the event
      of deterioration or complications. Health care utilization increased
      significantly after hospitalization. CONCLUSION: Most patients had not visited
      any health care facility within 30 days before hospitalization. Health care
      utilization increased significantly after hospitalization. Flaws in the
      continuity of care were found; even though most patients received written
      information at discharge, one third of the patients lacked knowledge about which
      health care provider to contact in the event of deterioration and felt insecure
      at home after discharge.

PMID- 30103689
TI  - Prevalence of normoalbuminuric renal insufficiency and associated clinical
      factors in adult onset diabetes.
AB  - BACKGROUND: Microalbuminuria signifies the onset of diabetic nephropathy, but
      normoalbuminuric patients with diabetes who have a low Glomerular Filtration Rate
      (GFR) are not uncommon. The purpose of the study was to estimate the prevalence
      of such patients and to assess the clinical correlates. METHODS: Cross-sectional
      study included patients with diabetes attending medical clinics at Teaching
      Hospital Galle. Diagnosis of albuminuria was made if urinary albumin excretion
      was > 30 mg/g of creatinine in two out of three samples. Patients were stratified
      into chronic kidney disease stages according to the estimated GFR (eGFR)
      calculated by Modification of Diet in Renal Disease (MDRD). RESULTS: Mean (SD)
      age and duration of the disease of 456 (348 females) patients with diabetes were
      60 (12) years and 10 (4) years. Sixty (13.2%) patients had low eGFR and 26.7% of
      them had normoalbuminuria. In the total sample, the proportion of patients with
      low eGFR and normoalbuminuria was 16 (3.5%). Among the patients with
      normoalbuminuria and low eGFR, 12.5% had retinopathy and none had any form
      neuropathy. When age, duration of disease, systolic and diastolic blood
      pressures, smoking, glycaemic control, presence of hypertension and ischaemic
      heart disease were included in binary logistic regression model, only age was
      found to be significant different (OR = 1.1, P = 0.03). CONCLUSION: A
      considerable proportion of adult diabetics are normoalbuminuric despite low eGFR.
      This limits the role of microalbuminuria as a screening tool to detect the onset
      of diabetic nephropathy. These patients do not exhibit distinct clinical features
      that facilitate identification of them using clinical information.

PMID- 30103687
TI  - Breath test using 13C methacetin does not seem to be useful in the assessment of
      liver function in girls with anorexia nervosa: a case control study.
AB  - BACKGROUND: Anorexia nervosa (AN) concerns approximately up to 1.8% of the
      pediatric female population. One of the complications that can occur in the
      course of this disease is acute liver failure. This study's objective was to
      assess the usefulness of the 13C labeled Methacetin Breath Test (MBT) in the
      diagnostics of the liver function in girls with eating disorders. METHODS: For
      the study 81 girls aged 12 to 17 years were recruited, including 41 patients with
      confirmed diagnosis of AN (mean age 14.7 +/- 1.48 years) and 40 age-matched
      controls. The diagnosis was based on the present Diagnostic and Statistical
      Manual of Mental Disorders (DSM-5) criteria. Weight and height were measured in
      all study participants and the Body Mass Index (BMI) was calculated. In the study
      and control group laboratory tests assessing the liver function and the MBT were
      performed. RESULTS: In all controls the anthropometric as well as laboratory
      liver function parameters were normal. In the study group 25 patients (61%) had
      BMI below the lower limit for age. The total percentage of 13CO2 recovery in the
      120th minute of the test did not exceed the lower limit in patients and controls.
      A result of the 13CO2 cumulative recovery above the upper normal range was found
      in 18 girls with AN (44% of the study group) and 2 controls (5%). Patients with
      AN were characterized by significantly higher 13CO2 cumulative dose recovery
      after ingestion of the substrate in comparison to the control group in all time
      points of the test. CONCLUSIONS: The obtained results confirm a significant
      stimulation of the liver metabolism of 13C labeled methacetin in female patients
      with AN. The increased cumulative dose recovery of the substrate in girls with AN
      impacts the credibility of this measurement and implies a risk of false negative
      results.

PMID- 30103690
TI  - Using Baidu index to nowcast hand-foot-mouth disease in China: a meta learning
      approach.
AB  - BACKGROUND: Hand, foot, and mouth disease (HFMD) has been recognized as one of
      the leading infectious diseases among children in China, which causes hundreds of
      annual deaths since 2008. In China, the reports of monthly HFMD cases usually
      have a delay of 1-2 months due to the time needed for collecting and processing
      clinical information. This time lag is far from optimal for policymakers making
      decisions. To alleviate this information gap, this study uses a meta learning
      framework and combines publicly Internet-based information (Baidu search queries)
      for real-time estimation of HFMD cases. METHODS: We incorporate Baidu index into
      modeling to nowcast the monthly HFMD incidences in Guangxi, Zhejiang, Henan
      provinces and the whole China. We develop a meta learning framework to select
      appropriate predictive model based on the statistical and time series meta
      features. Our proposed approach is assessed for the HFMD cases within the time
      period from July 2015 to June 2016 using multiple evaluation metrics including
      root mean squared error (RMSE) and correlation coefficient (Corr). RESULTS: For
      the four areas: whole China, Guangxi, Zhejiang, and Henan, our approach is
      superior to the best competing models, reducing the RMSE by 37, 20, 20, and 30%
      respectively. Compared with all the alternative predictive methods, our estimates
      show the strongest correlation with the observations. CONCLUSIONS: In this study,
      the proposed meta learning method significantly improves the HFMD prediction
      accuracy, demonstrating that: (1) the Internet-based information offers the
      possibility for effective HFMD nowcasts; (2) the meta learning approach is
      capable of adapting to a wide variety of data, and enables selecting appropriate
      method for improving the nowcasting accuracy.

PMID- 30103691
TI  - Hospitalization rates and outcome of invasive bacterial vaccine-preventable
      diseases in Tuscany: a historical cohort study of the 2000-2016 period.
AB  - BACKGROUND: Invasive bacterial diseases (IBD) are a serious cause of
      hospitalization, sequelae and mortality. Albeit a low incidence, an increase in
      cases due to H. influenzae was registered in the past 4 years and, in the Tuscany
      region, an excess of cases due to N. meningitidis since 2015 is alarming. The
      purpose of this study is to deepen the knowledge of IBD epidemiology in Tuscany
      with particular attention to temporal trends. METHODS: Tuscan residents
      hospitalized for IBD from January 1st 2000 to March 18th 2016 were selected from
      the regional hospital discharge database based on ICD-9-CM codes. Age-specific
      and standardized hospitalization rates were calculated together with case
      fatality rates (CFRs). A time-trend analysis was performed; whereas, prognostic
      factors of death were investigated through univariable and multivariable
      analyses. RESULTS: The average standardized hospitalization rates for invasive
      meningococcal diseases (IMD), invasive pneumococcal diseases and invasive
      diseases due to H. influenzae from 2000 to 2016 were 0.6, 1.8, and 0.2 per
      100,000, respectively. The average CFRs were 10.5%, 14.5% and 11.5% respectively
      with higher values in the elderly. Older age was significantly associated with
      higher risk of death from all IBD. A significant reduction in hospitalization
      rates for IMD was observed after meningococcal C conjugate vaccine introduction.
      The Annual Percentage Change (APC) was -13.5 (95% confidence interval (CI) -22.3;
      -3.5) in 2005-2013 but has risen since that period. Furthermore, a significant
      increasing trend of invasive diseases due to H. influenzae was observed from 2005
      onwards in children 1-4 years old (APC 13.3; 95% CI 0; 28.3). CONCLUSIONS: This
      study confirms changes in the epidemiology of invasive diseases due to H.
      influenzae and IMD. Furthermore, attention is called to the prevention of IBD in
      the elderly because of the age group's significantly higher rate of
      hospitalizations and deaths for all types of IBD.

PMID- 30103692
TI  - Implementing advance care planning in nursing homes - study protocol of a cluster
      randomized clinical trial.
AB  - BACKGROUND: Close to half of all deaths in Norway occur in nursing homes, which
      signals a need for good communication on end-of-life care. Advance care planning
      (ACP) is one means to that end, but in Norwegian nursing homes, ACP is not
      common. This paper describes the protocol of a project evaluating an ACP
      intervention in Norwegian nursing homes. The aims of this research project were
      to promote the possibility for conversations about the end of life with patients
      and relatives; promote patient autonomy; create a better foundation for important
      decisions in the case of medical emergencies and at the end of life; and gain
      experiences in order to find out what characterizes good ACP and good
      implementation strategies. METHODS/DESIGN: This study was a mixed method study
      including a cluster-randomized clinical trial. Eight nursing home wards or
      "clusters" were pair-matched, and one ward from each pair was randomly selected
      for a 12-month intervention. The intervention consisted of implementing an ACP
      guideline. Implementation strategies were training and supervision of project
      teams and staff in using the guideline, written information to patients and next
      of kin, and information meetings with nursing home staff. The project was
      evaluated using both quantitative and qualitative data, and both outcome and
      process evaluation. Quantitative data included patient chart reviews of ACP,
      diagnoses, patient preferences for decision-making and treatment, values and
      wishes that are more general, documented life-prolonging treatment and
      hospitalizations, and concordance between patient wishes and treatment. The
      primary outcome was documented ACP. Qualitative data included observations of
      conversations, interviews with patients, next of kin and health care personnel,
      logs from project coordinators and conversations, and transcripts from meetings
      with project teams in the intervention group. DISCUSSION: This project attempted
      to increase the quality and use of ACP in Norwegian nursing homes (NH). A mixed
      methods approach, inclusion of patients with dementia, attempts to involve, as
      many patients as possible, and a sustainable implementation plan adapted to real
      life in nursing homes were strengths of the project.

PMID- 30103693
TI  - CMV on surfaces in homes with young children: results of PCR and viral culture
      testing.
AB  - BACKGROUND: Caring for young children is a known risk factor for cytomegalovirus
      (CMV) infection mainly through exposure to their saliva and urine. In a previous
      study, 36 CMV-seropositive children 2 mo. to 4 years old were categorized as CMV
      shedders (n = 23) or non-shedders (n = 13) based on detection of CMV DNA in their
      saliva and urine. The current study evaluated the presence of CMV on surfaces in
      homes of the children. METHODS: Study staff made 4 visits to homes of the 36
      enrolled children over 100 days. Saliva was collected by swabbing the mouth and
      urine was collected on filter paper inserted into diapers. In addition, five
      surface specimens were collected: three in contact with children's saliva (spoon,
      child's cheek, washcloth) and two in contact with children's urine (diaper
      changing table, mother's hand). Samples were tested by PCR and viral culture to
      quantify the presence of CMV DNA and viable virus. RESULTS: A total of 654
      surface samples from 36 homes were tested; 136 were CMV DNA positive, 122 of
      which (90%) were in homes of the children shedding CMV (p < 0.001). Saliva
      associated samples were more often CMV positive with higher viral loads than
      urine-associated samples. The higher the CMV viral load of the child in the home,
      the more home surfaces that were PCR positive (p = 0.01) and viral culture
      positive (p = 0.05). CONCLUSIONS: The main source for CMV on surfaces in homes
      was saliva from the child in the home. Higher CMV viral loads shed by children
      correlated with more viable virus on surfaces which could potentially contribute
      to viral transmission.

PMID- 30103696
TI  - Undernutrition, intestinal parasitic infection and associated risk factors among
      selected primary school children in Bahir Dar, Ethiopia.
AB  - BACKGROUND: Monitoring of undernutrition and parasitic infection are essential to
      design appropriate intervention strategies. The aim of this study was to assess
      the prevalence of undernutrition, intestinal parasitic infection and their
      associated risk factors among school children in Bahir Dar, Ethiopia. METHODS: A
      school-based cross-sectional survey was conducted from February to June 2014
      among 382 students selected from primary schools in Bahir Dar. The study subjects
      were selected by a systematic random sampling method. Sociodemographic data from
      students and their family/guardians were obtained using structured questionnaire.
      Height and weight of the students were measured using a standard calibrated
      balance. Fresh fecal samples were collected and processed using formalin-ether
      concentration technique. The data were analyzed using SPSS version 20.0
      statistical software. RESULTS: The overall prevalence of undernutrition was 41.6%
      (18.3% stunted, 26.7% thinness and 25.9% underweight). Meal frequency <= 3 times
      a day (AOR=4.11; 95% CI: 2.23-7.59) and family monthly income <500 birr
      (AOR=5.87; 95% CI: 2.61-13.23) were important predictors of undernutrition. The
      risk of stunting was increased among students with meal frequency <= 3 times a
      day (AOR=5.56; 95% CI: 2.97-10.41) and age ranges from 9-10 years (AOR=3.02; 95%
      CI: 1.41-6.47). The odds of thinness was significantly increased among students
      with parasitic infection (AOR=1.92; 95% CI: 1.15-3.19) and family monthly income
      <1500 birr (AOR=2.69; 95% CI: 1.16-6.26). The likelihood of being underweight was
      increased among students infected with intestinal parasites (AOR=2.43; 95% CI:
      1.40-4.22). The overall prevalence of intestinal parasitosis was 52.4%. The risk
      of parasitic infection was significantly increased among students with unclean
      fingernails (AOR=4.96; 95% CI: 2.79-8.82) and irregular hand washing habit
      (AOR=8.05; 95% CI: 4.66-13.89). CONCLUSIONS: This study revealed that
      undernutrition and intestinal parasitic infection were public health problems
      among school children in the study areas. These results highlight the importance
      for integrated efforts to address undernutrition and parasitic infection.

PMID- 30103695
TI  - The Swiss Multiple Sclerosis Registry (SMSR): study protocol of a participatory,
      nationwide registry to promote epidemiological and patient-centered MS research.
AB  - BACKGROUND: Multiple sclerosis (MS) is one of the most frequently observed
      neurological conditions in Switzerland, but data sources for country-wide
      epidemiological trend monitoring are lacking. Moreover, while clinical and
      laboratory MS research are generally well established, there is a gap in patient
      centered MS research to inform care management, or treatment decisions and policy
      making not only in Switzerland but worldwide. METHODS: In light of these research
      gaps, the Swiss Multiple Sclerosis Society initiated and funded the Swiss
      Multiple Sclerosis Registry (SMSR) an open-ended, longitudinal and prospective,
      nationwide, patient-centered study. The SMSR recruits adult persons with a
      suspected or confirmed MS diagnosis who reside or receive care in Switzerland.
      The SMSR has established a governance structure with clear rules and guidelines.
      It follows a citizen-science approach with direct involvement of persons with MS
      (PwMS), who contribute actively to registry development, operations, and
      research. Main scientific goals entail the study of MS epidemiology in
      Switzerland, health care access and provision, as well as life circumstances and
      wellbeing of persons with MS. The innovative study design ("layer model") offers
      several participation options with different time commitments. Data collection is
      by means of regular surveys and medical record abstraction. Survey participation
      is offered in different modes (web, paper & pencil) and in the three main
      national languages (German, French, Italian). Participants also receive regular
      data feedbacks for personal use and self-monitoring, contextualized in the whole
      population of study participants. Data feedbacks are also used to solicit data
      corrections of key variables from participants. DISCUSSION: The SMSR combines the
      advantages of traditional and novel research methods in medical research and has
      recruited over 1600 PwMS in its first year. The future-oriented design and
      technology will enable a response not only to future technological innovations
      and research trends, but also to challenges in health care provision for MS.
      TRIAL REGISTRATION: ClinicalTrials.gov   NCT02980640 ; December 6, 2016;
      retrospectively registered.

PMID- 30103694
TI  - Leukotoxin and pyrogenic toxin Superantigen gene backgrounds in bloodstream and
      wound Staphylococcus aureus isolates from eastern region of China.
AB  - BACKGROUND: The bicomponent leukotoxins and the pyrogenic toxin superantigens
      (PTSAgs) are important virulence factors of Staphylococcus aureus. It is
      necessary to survey the prevalence and expression of these toxin-encoding genes
      for understanding the possible pathogenic capacity of S. aureus to cause disease.
      METHODS: Five leukotoxin genes and thirteen PTSAg determinants were detected for
      177 S. aureus isolates from blood (n = 88) and wound (n = 89) infections by
      Polymerase Chain Reaction (PCR). The expression of leukotoxin ED (lukED) was
      determined by quantitative real-time PCR (qRT-PCR). The genetic backgrounds of
      isolates were analyzed by Staphylococcal Cassette Chromosome mec (SCCmec) typing
      (for methicillin-resistant S. aureus isolates), Pulsed-Field Gel Electrophoresis
      (PFGE), accessory gene regulator (agr) typing and Multilocus Sequence Typing
      (MLST, for representative isolates based on PFGE type) methods. RESULTS: 99.4%
      (176/177) isolates contained at least one of leukotoxin genes. Among them, 94.9%
      (168/177), 81.4% (144/177) and 67.8% (120/177) isolates harbored hlgBC, lukED and
      lukAB, respectively. Compared to leukotoxin genes, there was a relatively lower
      overall prevalence of PTSAg genes [99.4% versus 72.9% (129/177), P < 0.001], and
      they were organized in 59 patterns, with the most common combination of the egc
      cluster with or without other PTSAg genes. Genetic analysis showed the
      distributions of certain toxin genes were associated with the genetic backgrounds
      of isolates. The egc cluster was a common feature of CC5 isolates, among which
      ST5 and ST764 isolates harbored more PTSAg genes. The lukED was not present in
      ST398 isolates, and its expression was quite different among isolates. No
      significant correlations were observed between the lukED expression levels of
      strains and the ST or agr types. CONCLUSIONS: The present study elucidated the
      distribution of leukotoxin and PTSAg genes and the expression of lukED in blood
      and wound isolates, and analyzed the relationship between them with genetic
      characteristics of isolates. These data improve the current understanding of the
      possible pathogenicity of S. aureus.

PMID- 30103697
TI  - Early life stress and frailty in old age: the Helsinki birth cohort study.
AB  - BACKGROUND: Evidence suggests that early life stress (ELS) may extend its effect
      into adulthood and predispose an individual to adverse health outcomes. We
      investigated whether wartime parental separation, an indicator of severe ELS,
      would be associated with frailty in old age. METHODS: Of the 972 participants
      belonging to the present sub-study of the Helsinki Birth Cohort Study, 117
      (12.0%) had been evacuated abroad unaccompanied by their parents in childhood
      during World War II. Frailty was assessed at a mean age of 71 years according to
      Fried's criteria. RESULTS: Thirteen frail men (4 separated and 9 non-separated)
      and 20 frail women (2 separated and 18 non-separated) were identified. Compared
      to the non-separated men, men who had been separated had an increased relative
      risk ratio (RRR) of frailty (age-adjusted RRR 3.93, 95% CI 1.02, 15.11) that
      persisted after adjusting for several confounders. No associations were observed
      among women (RRR 0.62; 95% CI 0.13, 2.94). CONCLUSIONS: These preliminary results
      suggest that ELS might extend its effects not just into adulthood but also into
      old age, and secondly, that men may be more vulnerable to the long-term effects
      of ELS.

PMID- 30103698
TI  - Molecular investigation of isolates from a multistate polymicrobial outbreak
      associated with contaminated total parenteral nutrition in Brazil.
AB  - BACKGROUND: Between November 2013 and June 2014, 56 cases of bacteremia (15
      deaths) associated with the use of Total Parenteral Nutrition (TPN) and/or
      calcium gluconate (CG) were reported in four Brazilian states. METHODS: We
      analyzed 73 bacterial isolates from four states: 45 from blood, 25 from TPN and
      three from CG, originally identified as Acinetobacter baumannii, Rhizobium
      radiobacter, Pantoea sp. or Enterobacteriaceae using molecular methods. RESULTS:
      The first two bacterial species were confirmed while the third group of species
      could not be identified using standard identification protocols. These isolates
      were subsequently identified by Multi-Locus Sequence Analysis as Phytobacter
      diazotrophicus, a species related to strains from similar outbreaks in the United
      States in the 1970's. Within each species, TPN and blood isolates proved to be
      clonal, whereas the R. radiobacter isolates retrieved from CG were found to be
      unrelated. CONCLUSION: This is the first report of a three-species outbreak
      caused by TPN contaminated with A. baumannii, R. radiobacter and P.
      diazotrophicus. The concomitant presence of clonal A. baumannii and P.
      diazotrophicus isolates in several TPN and blood samples, as well as the case of
      one patient, where all three different species were isolated simultaneously,
      suggest that the outbreak may be ascribed to a discrete contamination of TPN. In
      addition, this study highlights the clinical relevance of P. diazotrophicus,
      which has been involved in outbreaks in the past, but was often misidentified as
      P. agglomerans.

PMID- 30103700
TI  - TaNBP1, a guanine nucleotide-binding subunit gene of wheat, is essential in the
      regulation of N starvation adaptation via modulating N acquisition and ROS
      homeostasis.
AB  - BACKGROUND: Nitrate (NO3-) is the major source of nitrogen (N) for higher plants
      aside from its function in transducing the N signaling. Improving N use
      efficiency of crops has been an effective strategy for promotion of the
      sustainable agriculture worldwide. The regulatory pathways associating with N
      uptake and the corresponding biochemical processes impact largely on plant N
      starvation tolerance. Thus, exploration of the molecular mechanism underlying
      nitrogen use efficiency (NUE) and the gene wealth will pave a way for molecular
      breeding of N starvation-tolerant crop cultivars. RESULTS: In the current study,
      we characterized the function of TaNBP1, a guanine nucleotide-binding protein
      subunit beta gene of wheat (T. aestivum), in mediating the plant N starvation
      response. TaNBP1 protein harbors a conserved W40 domain and the TaNBP1-GFP (green
      fluorescence protein) signals concentrate at positions of cytoplasm membrane and
      cytosol. TaNBP1 transcripts are induced in roots and leaves upon N starvation
      stress and that this upregulated expression is recovered by N recovery treatment.
      TaNBP1 overexpression confers improved phenotype, enlarged root system
      architecture (RSA), and increased biomass for plants upon N deprivation relative
      to the wild type, associating with its role in enhancing N accumulation and
      improving reactive oxygen species (ROS) homeostasis. Nitrate transporter (NRT)
      gene NtNRT2.2 and antioxidant enzyme genes NtSOD1, NtSOD2, and NtCAT1 are
      transcriptionally regulated under TaNBP1 and contribute to the improved N
      acquisition and the increased AE activities of plants. CONCLUSIONS: Altogether,
      TaNBP1 is transcriptional response to N starvation stress. Overexpression of this
      gene enhances plant N starvation adaptation via improvement of N uptake and
      cellular ROS homeostasis by modifying transcription of NRT gene NtNRT2.2 and
      antioxidant enzyme genes NtSOD1, NtSOD2, and NtCAT1, respectively. Our research
      helps to understand the mechanism underlying plant N starvation response and
      benefits to genetically engineer crop cultivars with improved NUE under the N
      saving cultivation conditions.

PMID- 30103701
TI  - MITE insertion-dependent expression of CitRKD1 with a RWP-RK domain regulates
      somatic embryogenesis in citrus nucellar tissues.
AB  - BACKGROUND: Somatic embryogenesis in nucellar tissues is widely recognized to
      induce polyembryony in major citrus varieties such as sweet oranges, satsuma
      mandarins and lemons. This capability for apomixis is attractive in agricultural
      production systems using hybrid seeds, and many studies have been performed to
      elucidate the molecular mechanisms of various types of apomixis. To identify the
      gene responsible for somatic embryogenesis in citrus, a custom oligo-DNA
      microarray including predicted genes in the citrus polyembryonic locus was used
      to compare the expression profiles in reproductive tissues between monoembryonic
      and polyembryonic varieties. The full length of CitRKD1, which was identified as
      a candidate gene responsible for citrus somatic embryogenesis, was isolated from
      satsuma mandarin and its molecular function was investigated using transgenic
      'Hamlin' sweet orange by antisense-overexpression. RESULTS: The candidate gene
      CitRKD1, predominantly transcribed in reproductive tissues of polyembryonic
      varieties, is a member of the plant RWP-RK domain-containing protein. CitRKD1 of
      satsuma mandarin comprised two alleles (CitRKD1-mg1 and CitRKD1-mg2) at the
      polyembryonic locus controlling embryonic type (mono/polyembryony) that were
      structurally divided into two types with or without a miniature inverted-repeat
      transposable element (MITE)-like insertion in the upstream region. CitRKD1-mg2
      with the MITE insertion was the predominant transcript in flowers and young
      fruits where somatic embryogenesis of nucellar cells occurred. Loss of CitRKD1
      function by antisense-overexpression abolished somatic embryogenesis in
      transgenic sweet orange and the transgenic T1 plants were confirmed to derive
      from zygotic embryos produced by self-pollination by DNA diagnosis. Genotyping
      PCR analysis of 95 citrus traditional and breeding varieties revealed that the
      CitRKD1 allele with the MITE insertion (polyembryonic allele) was dominant and
      major citrus varieties with the polyembryonic allele produced polyembryonic
      seeds. CONCLUSION: CitRKD1 at the polyembryonic locus plays a principal role in
      regulating citrus somatic embryogenesis. CitRKD1 comprised multiple alleles that
      were divided into two types, polyembryonic alleles with a MITE insertion in the
      upstream region and monoembryonic alleles without it. CitRKD1 was transcribed in
      reproductive tissues of polyembryonic varieties with the polyembryonic allele.
      The MITE insertion in the upstream region of CitRKD1 might be involved in
      regulating the transcription of CitRKD1.

PMID- 30103699
TI  - Transcriptome sequencing to detect the potential role of long non-coding RNAs in
      bovine mammary gland during the dry and lactation period.
AB  - BACKGROUND: It is known that long non-coding RNAs (lncRNAs) play an important
      role in various biological processes, including cell proliferation,
      differentiation and apoptosis. However, their functions and profiles in lactation
      cycle of dairy cows are largely unknown. In this study, lncRNA-seq technique was
      employed to compare the expression profiles of lncRNAs and mRNAs from Chinese
      Holstein mammary gland in dry and lactation period. RESULT: Totally 3746
      differentially expressed lncRNAs (DELs) and 2890 differentially expressed genes
      (DEGs) were identified from the dry and lactation mammary glands of Holstein
      cows. Functional enrichment analysis on target genes of lncRNAs indicated that
      these genes were involved in lactation-related signaling pathways, including cell
      cycle, JAK-STAT, cell adhesion, and PI3K-Akt signaling pathways. Additionally,
      the interaction between lncRNAs and their potential miRNAs was predicted and
      partly verified. The result indicated that the lactation-associated miR-221 might
      interact with lncRNAs TCONS_00040268, TCONS_00137654, TCONS_00071659 and
      TCONS_00000352, which revealed that these lncRNAs might be important regulators
      for lactation cycle. CONCLUSION: This study provides a resource for lncRNA
      research on lactation cycle of bovine mammary gland. Besides, the interaction
      between lncRNAs and the specific miRNA is revealed. It expands our knowledge
      about lncRNA and miRNA biology as well as contributes to clarify the regulation
      of lactation cycle of bovine mammary gland.

PMID- 30103702
TI  - Unsupervised correction of gene-independent cell responses to CRISPR-Cas9
      targeting.
AB  - BACKGROUND: Genome editing by CRISPR-Cas9 technology allows large-scale screening
      of gene essentiality in cancer. A confounding factor when interpreting CRISPR
      Cas9 screens is the high false-positive rate in detecting essential genes within
      copy number amplified regions of the genome. We have developed the computational
      tool CRISPRcleanR which is capable of identifying and correcting gene-independent
      responses to CRISPR-Cas9 targeting. CRISPRcleanR uses an unsupervised approach
      based on the segmentation of single-guide RNA fold change values across the
      genome, without making any assumption about the copy number status of the
      targeted genes. RESULTS: Applying our method to existing and newly generated
      genome-wide essentiality profiles from 15 cancer cell lines, we demonstrate that
      CRISPRcleanR reduces false positives when calling essential genes, correcting
      biases within and outside of amplified regions, while maintaining true positive
      rates. Established cancer dependencies and essentiality signals of amplified
      cancer driver genes are detectable post-correction. CRISPRcleanR reports sgRNA
      fold changes and normalised read counts, is therefore compatible with downstream
      analysis tools, and works with multiple sgRNA libraries. CONCLUSIONS:
      CRISPRcleanR is a versatile open-source tool for the analysis of CRISPR-Cas9
      knockout screens to identify essential genes.

PMID- 30103703
TI  - The effect of intracerebroventricular administration of orexin receptor type 2
      antagonist on pentylenetetrazol-induced kindled seizures and anxiety in rats.
AB  - BACKGROUND: Current antiepileptic drugs are not able to prevent recurrent
      seizures in all patients. Orexins are excitatory hypothalamic neuropeptides that
      their receptors (Orx1R and Orx2R) are found almost in all major regions of the
      brain. Pentylenetetrazol (PTZ)-induced kindling is a known experimental model for
      epileptic seizures. The purpose of this study was to evaluate the effect of Orx2
      receptor antagonist (TCS OX2 29) on seizures and anxiety of PTZ-kindled rats.
      RESULTS: Our results revealed that similar to valproate, administration of 7
      ug/rat of TCS OX2 29 increased the latency period and decreased the duration time
      of 3rd and 4th stages of epileptiform seizures. Besides, it significantly
      decreased mean of seizure scores. However, TCS OX2 29 did not modulate anxiety
      induced by repeated PTZ administration. CONCLUSION: This study showed that
      blockade of Orx2 receptor reduced seizure-related behaviors without any
      significant effect on PTZ-induced anxiety.

PMID- 30103704
TI  - Factors associated with spontaneous preterm birth in Addis Ababa public
      hospitals, Ethiopia: cross sectional study.
AB  - BACKGROUND: Spontaneous preterm birth is commencement of labor with intact or pre
      labor rapture of membrane and birth before 37 weeks of gestation. The aim of this
      study was to identify common factors associated with spontaneous preterm birth in
      Addis Ababa public hospitals. METHODS: After random selection of three hospitals
      from the six Addis Ababa's Public hospitals having Neonatal intensive care unit,
      systematic sampling was employed to select study units from admission log book of
      the neonates. Data were collected using structured checklist. Finally, data
      entered to EpiData 3.1 and transported to SPSS 22 for analysis. Bivariate and
      multivariate logistic regression analysis was done for the variables. RESULT: The
      mean gestational age of preterm birth was 32.45 (+/-2.903 SD). Majority (66.1%)
      of preterm births were spontaneous and 33.9% were induced preterm births.
      Hypertension during pregnancy [P = 0.001, AOR = 0.182, 95% CI: (0.067, 0.493)]
      and maternal HIV infection [P = 0.041, AOR = 3.408 95% CI: (1.048, 11.079)]
      significantly associated with spontaneous preterm birth. CONCLUSION: Those
      mothers who were diagnosed with hypertension during pregnancy less likely gave
      spontaneous preterm birth than who had no history of hypertension during
      pregnancy and HIV positive mothers gave spontaneous preterm more likely than HIV
      negative mothers. Thus, giving emphasis to these factors with appropriate care
      during pregnancy is important to reduce spontaneous preterm birth.

PMID- 30103705
TI  - Pain and self-rated health among middle-aged and older Canadians: an analysis of
      the Canadian community health survey-healthy aging.
AB  - BACKGROUND: Pain is an important health problem adversely affecting functionality
      and quality of life. Though self- rated health (SRH) is a major predictor of
      mortality, its relationship with pain is not well understood. We explore 1) how
      pain and age interact to influence SRH, and 2) provincial variations in SRH
      across Canada. METHODS: We analyzed cross-sectional data from Statistics Canada's
      Canadian Community Health Survey-Healthy Aging (n = 30,685), which targeted those
      45 years and older and was conducted from 2008 to 12-01 to 2009-11-30. The
      response rate was 74.4%.The topics covered included socio-demographics, well
      being and chronic diseases. We performed both bivariate and multivariate analyses
      between each predictor and SRH; unadjusted and adjusted odds ratios and 95%
      confidence intervals are reported. Two-level logistic regression mixed model was
      used to account for provincial differences. An intraclass correlation coefficient
      was also computed. RESULTS: Slightly more than half of respondents (56.40%) were
      female. In bivariate analyses, those experiencing pain had an odds ratio of 0.20.
      Which means that the odds of reporting good self-rated health are 4 to 5 times
      lower for those with pain, compare to the odds of reporting good self-rated
      health among those without pain (p < 0.001). In multivariate analyses the highly
      educated, female gender, the never married or single and households with high
      yearly income were predictors of good health (p < 0.001). Those who reported
      depressive symptoms, the lonely, the obese, daily smokers and/or the stressed
      were less likely to rate their health as good (p < 0.001). The influence of pain
      on SRH was stronger among younger age groups (45-54 years) compared to older age
      groups (75-84 years, with an odds ratio of 3.53 [p < 0.001] versus 3.14 [p <
      0.001]). CONCLUSIONS: Pain, among other determinants, is associated with SRH.
      Individuals in rating their health may consider a variety of factors, some of
      which may not be apparent to health providers. We found that those who reported
      depressive symptoms, were daily smokers, the obese, the lonely, and/or having a
      stressful life were less likely to rate their health as good. No significant
      provincial variations in SRH in Canada was observed in this study.

PMID- 30103706
TI  - Fathers' experiences of care when their partners suffer from peripartum
      cardiomyopathy: a qualitative interview study.
AB  - BACKGROUND: Peripartum cardiomyopathy (PPCM), a potentially life-threatening
      condition in women, can have a profound impact on the family. Although structured
      support systems are developed, these systems tend to be based on the healthcare
      providers' perceptions and focus mainly on mothers' care. Fathers' vital role in
      supporting their partners has been advocated in previous research. However, the
      impact of PPCM on the male partners of women is less understood. The aim of this
      study was to explore the experiences of healthcare in fathers whose partner was
      suffering from peripartum cardiomyopathy. METHODS: The data from interviews with
      fourteen fathers were analysed using inductive content analysis. RESULTS: An
      overarching category "The professionals could have made a difference" was
      identified from the data, characterised by the sub-categories: 'To be
      informed/not informed,' 'To feel secure/insecure,' 'To feel visible/invisible'
      and 'Wish that it had been different'. Lack of timely information did not allow
      fathers to understand their partner's distress, and plan for the future. The
      birth of the child was an exciting experience, but a feeling of helplessness was
      central, related to seeing their partner suffering. A desire for follow-up
      regarding the effect of PPCM on themselves was expressed. CONCLUSIONS: When men,
      as partners of women with PPCM, get adequate information of their partner's
      condition, they gain a sense of security and control that gives them strength to
      handle their personal and emotional life-situation during the transition of
      becoming a father, along with taking care of an ill partner with PPCM. Hence,
      maternity professionals should also focus on fathers' particular needs to help
      them fulfil their roles. Further research is urgently required in this area.

PMID- 30103707
TI  - Survival and prognostic analysis of preoperative inflammatory markers in patients
      undergoing surgical resection for laryngeal squamous cell carcinoma.
AB  - BACKGROUND: To estimate the prognostic value of inflammatory markers in patients
      with laryngeal squamous cell carcinoma (LSCC). METHODS: A total of 361 resected
      LSCC patients were included. The preoperative and postoperative neutrophil-to
      lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to
      lymphocyte ratio (MLR), alkaline phosphatase (ALP) and l actate dehydrogenase
      (LDH) were assessed. The Kaplan-Meier survival analysis and Cox regression
      analysis were conducted on overall survival (OS) and progression-free survival
      (PFS). RESULTS: Both Kaplan-Meier analysis and univariate analysis demonstrated
      significant prognostic value of preoperative and postoperative NLR, PLR and MLR.
      However, only preoperative ALP was predictive of OS and PFS, and LDH failed to be
      predictor of OS and PFS. The multivariate analysis showed that preoperative NLR
      (OS: HR = 1.64, 95%CI: 1.06-2.54, p = 0.026; PFS: HR = 1.52, 95%CI: 1.04-2.23, p
      = 0.029) and postoperative MLR (OS: HR = 2.02, 95%CI: 1.29-3.14, p = 0.002; PFS:
      HR = 1.57, 95%CI: 1.05-2.34, p = 0.026) were independently related with survival.
      CONCLUSIONS: The elevated preoperative NLR, PLR, MLR and ALP were significantly
      associated with worse survival and cancer progression. The preoperative NLR and
      postoperative MLR might be independent prognostic markers of OS and PFS in LSCC
      patients undergoing surgical resection.

PMID- 30103708
TI  - Awareness of retinopathy of prematurity among pediatricians in West Bank,
      Palestine: a descriptive study.
AB  - BACKGROUND: Retinopathy of prematurity (ROP) is a disorder of the developing
      retina of preterm infants due to defective vasculogenesis. The aim of the study
      was to analyze the level of awareness, knowledge, attitude and practice of
      pediatricians about ROP in the West Bank, Palestine. METHODS: A questionnaire was
      designed on the knowledge, attitude, and practice (KAP) pattern. The
      questionnaire included questions about pediatrician's educational and practicing
      profile, knowledge of screening guidelines, risk factors for ROP, referral
      facilities and barriers for referral. The questionnaire was given to70 practicing
      specialists and residents in hospitals having neonatal intensive care units in
      the West Bank, Palestine. It was a self-administered questionnaire, collected
      between November 2016 and February 2017. RESULTS: A total of 70 pediatricians
      from 11 different hospitals without ROP screening service participated in the
      study. The mean age of the participants was 33.04 +/- 7.74. Of which, 62.9% were
      males and 37.1% were females. Fifty-nine (84.3%) answered that ROP is
      preventable, while 11 (15.7%) responded that ROP is not preventable. Nine (12.9%)
      pediatricians had no idea as to which part of the eye is affected in ROP. Among
      the participants, 29 (41.4%) did not know when ROP screening should be started.
      Sixty-three (90%) pediatricians were sure that ROP is treatable. Regarding
      barriers for ROP screening, 'ophthalmologist not available' reason was expressed
      by 37.1% (26/70), 'discharge person not writing' by 20% (14/70) and 'parents not
      agreeing' by 18.6% (13/70) of the participants. Knowledge on the use of laser as
      a treatment modality of ROP was shown by 39 (55.7%) participants, and the use of
      anti-VEGF was shown by 6 (8.6%) participants, whereas 25 (35.7%) of the
      participants didn't know about the treatment modalities. CONCLUSION: The study
      findings suggest that a large majority of pediatricians were aware of ROP as a
      preventable disease, but had less information about ROP screening guidelines and
      service delivery. The study suggests the need to increase the awareness of
      pediatricians by dissemination of information about ROP and creating a close
      coordination between them and ophthalmologists to address barriers for service
      delivery in Palestine.

PMID- 30103709
TI  - Rational development of synergistic combinations of chemotherapy and molecular
      targeted agents for colorectal cancer treatment.
AB  - BACKGROUND: The irinotecan-induced phosphokinome changes in colorectal cancer
      (CRC) cells were used to guide the selection of targeted agents to be tested in
      combination with irinotecan. METHODS: Phosphokinome profiling with peptide arrays
      of tumour samples from nude mice xenografted with HT29 cells and treated or not
      with an effective dose of irinotecan was used to identify signalling pathways
      activated by irinotecan treatment. Then, drugs targeting these pathways were
      combined in vitro with irinotecan to test potential synergistic effect. The
      interactions between these drug combinations were assessed by a dose matrix
      approach. Confirmation of the most potential combination has been confirmed in
      vivo in xenografted mice. RESULTS: Irinotecan induced in vivo the activation of
      AKT and MEK1 phosphorylation. The dose matrix approach showed that BKM120 (PI3K
      inhibitor) and MEK162 (MEK inhibitor) are synergistic in vitro and in vivo with a
      cytostatic and cytotoxic effect, while combination of BKM120 and irinotecan or
      MEK162 and irinotecan are only additive or even antagonistic. However, the triple
      combination of SN38, BKM120 and MEK162 showed a better synergistic effect that
      BKM120 and MEK162, indicating that the cells need to inhibit both AKT and ERK
      pathways to become more sensitive to irinotecan-based chemotherapies. CONCLUSION:
      Analysis of chemotherapy-induced phosphokinome changes helps to elucidate the
      mechanisms of drug resistance and to guide the selection of targets for
      combination therapies with synergistic activity.

PMID- 30103710
TI  - CREB3L1 as a potential biomarker predicting response of triple negative breast
      cancer to doxorubicin-based chemotherapy.
AB  - BACKGROUND: Doxorubicin-based chemotherapy is currently the most frequently used
      treatment for triple negative breast cancer (TNBC), yet the response rate is not
      high due to the lack of a biomarker allowing identification of responsive
      patients before the chemotherapy is initiated. We have demonstrated that
      doxorubicin inhibits proliferation of cancer cells through proteolytic activation
      of a transcription factor called CREB3L1 (cAMP response element binding protein 3
      like 1), and that CREB3L1 expression in cancer cells is a key determinant of
      their sensitivity to doxorubicin when they are cultured in vitro or established
      as xenograft tumors in mice. The purpose of this study is to determine whether
      CREB3L1 expression in tumor cells of TNBC patients can be established as a
      biomarker to predict outcomes of doxorubicin-based chemotherapy. METHODS: We
      performed a retrospective analysis on breast core biopsy tissue samples taken
      from 18 TNBC patients before they were treated with doxorubicin-based
      chemotherapy. CREB3L1 expression in the cancer cells was analyzed by
      immunohistochemistry and quantified using the Immunoreactive Score (IRS).
      Outcomes of the chemotherapy were measured by the residual cancer burden (RCB)
      system. RESULTS: CREB3L1 expression levels in TNBC responsive to doxorubicin
      based chemotherapy (RCB class 0-2) were significantly higher than that in
      resistant cancers (RCB class 3) (unpaired two-tailed t test, p = 0.0005;
      Statistical power 99.8 at 95% confidence level). All cancers expressing higher
      levels of CREB3L1 (IRS 4-12) responded to doxorubicin-based chemotherapy, whereas
      all cancers resisting the treatment expressed lower levels of CREB3L1 (IRS 0-3).
      CONCLUSIONS: These results suggest that CREB3L1 expression level may be used as a
      biomarker to identify TNBC patients who are more likely to benefit from
      doxorubicin-based chemotherapy.

PMID- 30103711
TI  - The Prognosis in Palliative care Study II (PiPS2): study protocol for a multi
      centre, prospective, observational, cohort study.
AB  - BACKGROUND: More accurate methods of prognostication are likely to lead to
      improvements in the quality of care of patients approaching the ends of their
      lives. The Prognosis in Palliative care Scales (PiPS) are prognostic models of
      survival. The scores are calculated using simple clinical data and observations.
      There are two separate PiPS models; PiPS-A for patients without blood test
      results and PiPS-B for patients with blood test results. Both models predict
      whether a patient is likely to live for "days", "weeks" or "months" and have been
      shown to perform as well as clinicians' estimates of survival. PiPS-B has also
      been found to be significantly better than doctors' estimates of survival. We
      report here a protocol for the validation of PiPS and for the evaluation of the
      accuracy of other prognostic tools in a new, larger cohort of patients with
      advanced cancer. METHODS: This is a national, multi-centre, prospective,
      observational cohort study, aiming to recruit 1778 patients via palliative care
      services across England and Wales. Eligible patients have advanced, incurable
      cancer and have recently been referred to palliative care services. Patients with
      or without capacity are included in the study. The primary outcome is the
      accuracy of PiPS predictions and the difference in accuracy between these
      predictions and the clinicians' estimates of survival; with PiPS-B being the main
      model of interest. The secondary outcomes include the accuracy of predictions by
      the Palliative Prognostic Index (PPI), Palliative Performance Scale (PPS),
      Palliative Prognostic score (PaP) and the Feliu Prognostic Nomogram (FPN)
      compared with actual patient survival and clinicians' estimates of survival. A
      nested qualitative sub-study using face-to-face interviews with patients, carers
      and clinicians is also being undertaken to assess the acceptability of the
      prognostic models and to identify barriers and facilitators to clinical use.
      DISCUSSION: The study closed to recruitment at the end of April 2018 having
      exceeded the required sample size of 1778 patients. The qualitative sub-study is
      nearing completion. This demonstrates the feasibility of recruiting large numbers
      of participants to a prospective palliative care study. TRIAL REGISTRATION:
      ISRCTN13688211 (registration date: 28/06/2016).

PMID- 30103713
TI  - MRI in predicting the response of gastrointestinal stromal tumor to targeted
      therapy: a patient-based multi-parameter study.
AB  - BACKGROUND: To investigate the performance of quantitative indicators of MRI in
      early prediction of the response of gastrointestinal stromal tumor (GIST) to
      targeted therapy in a patient-based study. METHODS: MRI examinations were
      performed on 62 patients with GIST using 1.5 T scanners before and at two and 12
      weeks after treatment with targeted agents. The longest diameter (LD) and
      contrast-to-noise ratio (CNR) of the tumors were measured by T2-weighted imaging
      (T2WI), and the apparent diffusion coefficient (ADC) was determined using
      diffusion-weighted imaging (DWI). The pre-therapy and early percentage changes
      (%Delta) of the three parameters were compared with regard to their abilities to
      differentiate responder and non- responder patients, using ROC curves. RESULTS:
      There were 42 patients in responder and 20 in non-responder group. After two
      weeks of therapy, the percentage changes in the ADC and LD were significantly
      different between the two groups (ADC: responder 30% vs. non- responder 1%, Z = -
      4.819, P < 0.001; LD: responder - 7% vs. non- responder - 2%, Z = - 3.238, P =
      0.001), but not in T2WI-CNR (responder - 3% vs. non-responder 9%, Z = - 0.663, P
      = 0.508). The AUCs on ROC for %DeltaLD, %DeltaT2WI-CNR and %DeltaADC after two
      weeks of therapy were 0.756, 0.552 and 0.881, respectively, for response
      differentiation. When %DeltaADC >=15% was used to predict responder, the PPV was
      93.3%. CONCLUSIONS: The percentage change of the ADC after two weeks of therapy
      outperformed T2WI-CNR and longest diameter in predicting the early response of
      GIST to targeted therapy.

PMID- 30103714
TI  - Gender specific association between the use of complementary and alternative
      medicine (CAM) and alcohol consumption and injuries caused by drinking in the
      sixth Tromso study.
AB  - BACKGROUND: Alcohol is consumed almost worldwide and is the most widely used
      recreational drug in the world. Harmful use of alcohol is known to cause a large
      disease-, social- and economic burden on society. Only a few studies have
      examined the relationship between CAM use and alcohol consumption. To our
      knowledge there has been no such research in Norway. The aim of this study is to
      describe and compare alcohol consumption and injuries related to alcohol across
      gender and different CAM approaches. METHODS: The data used in this study is
      based on questionnaire data gathered from the sixth Tromso Study conducted
      between 2007 and 2008. Information on CAM use and alcohol consumption was
      available for 6819 women and 5994 men, 64.8% of the invited individuals. Pearson
      chi-square tests and independent sample t-tests were used to describe the basic
      characteristics of the participants and to calculate the differences between men
      and women regarding these variables. Binary logistic regression analyses were
      used to investigate the associations between the different CAM approaches and
      alcohol consumptions and injuries caused by drinking. RESULTS: Women who drank
      alcohol more than once a month were more likely to have applied herbal or
      "natural" medicine and self-treatment techniques (meditation, yoga, qi gong or
      tai-chi), compared to those who never drank, and those who only drank monthly or
      less. For women, an association was also found between having experienced
      injuries caused by drinking and use of self-treatment techniques and visit to a
      CAM practitioner. No association was found between amount of alcohol consumed and
      use of CAM approaches. For men, an association was found between injuries caused
      by drinking and use of herbal or "natural" medicine. CONCLUSION: The findings
      from this cross-sectional study suggests that women who drink frequently are more
      likely to use "natural" medicine and self-treatment techniques. Both men and
      women who had experienced injuries because of their drinking were more likely to
      have used CAM approaches.

PMID- 30103712
TI  - Hornerin promotes tumor progression and is associated with poor prognosis in
      hepatocellular carcinoma.
AB  - BACKGROUND: The function of hornerin (HRNR), a member of the S100 protein family,
      is poorly clarified in the development of human tumors. The role of HRNR in
      hepatocellular carcinoma (HCC) progression is investigated in the study. METHODS:
      The expression levels of HRNR were assessed in tumor samples from a cohort of 271
      HCC patients. The effect of HRNR on proliferation, colony formation and invasion
      of tumor cells was examined. We further determined the role of HRNR in tumor
      growth in vivo by using xenograft HCC tumor models. The possible mechanism of the
      HRNR promotion of HCC progression was explored. RESULTS: We found that HRNR was
      overexpressed in HCC tissues. The high expression of HRNR in HCCs was
      significantly associated with vascular invasion, poor tumor differentiation, and
      advanced TNM stage. The disease-free survival (DFS) and overall survival (OS) of
      HCC patients with high HRNR expression were poorer than those in the low HRNR
      expression group. HRNR expression was an independent risk factor linked to both
      poor DFS (HR = 2.209, 95% CI = 1.627-2.998,P <  0.001) and OS (HR = 2.459,95% CI
      = 1.736-3.484, P <  0.001). In addition, the knockdown of HRNR by shRNAs
      significantly inhibited the proliferation, colony formation, migration and
      invasion of HCC tumor cells. HRNR silencing led to the decreased phosphorylation
      of AKT signaling. Notably, tumor growth was markedly inhibited by HRNR silencing
      in a xenograft model of HCC. CONCLUSIONS: HRNR promotes tumor progression and is
      correlated with a poor HCC prognosis. HRNR may contribute to HCC progression via
      the regulation of the AKT pathway.

PMID- 30103715
TI  - Radiocarpal fusion and midcarpal resection interposition arthroplasty: long-term
      results in severely destroyed rheumatoid wrists.
AB  - BACKGROUND: The aim of this retrospective study is to evaluate distal resection
      interposition arthroplasty of the wrist as a tool to restore mobility as well as
      to restore stability in severely destroyed wrist joints. METHODS: Thirty-four
      wrists in 28 rheumatoid arthritis patients were included. The mean follow-up time
      was 9 years after surgical treatment with clinical and radiological examination.
      The results were accessed based on a modification of Clayton s scoring system as
      well as a functional questionnaire. RESULTS: 71% patients were satisfied with
      pain, function and activities of daily life. Better results were reported by
      patients with a young age, early surgical intervention, a shorter duration of the
      disease, and lesser involvement of other joints. CONCLUSIONS: The results for
      radiocarpal arthrodesis were comparable to those of synovectomy or arthrodesis of
      the wrist. The results after total wrist joint arthroplasty varies probably as
      the result of different patient groups, implant types and evolution of prosthetic
      designs, and are not comparable with the present study.

PMID- 30103716
TI  - Population-level factors associated with maternal mortality in the United States,
      1997-2012.
AB  - BACKGROUND: In contrast to peer nations, the United States is experiencing rapid
      increases in maternal mortality. Trends in individual and population-level
      demographic factors and health trends may play a role in this change. METHODS: We
      analyzed state-level maternal mortality for the years 1997-2012 using multilevel
      mixed-effects regression grouped by state, using publicly available data
      including whether a state had adopted the 2003 U.S. Standard Certificate of
      Death, designed to simplify identification of pregnant and recently pregnant
      decedents. We calculated the proportion of the increase in maternal mortality
      attributable to specific factors during the study period. RESULTS: Maternal
      mortality was associated with higher population prevalence of obesity and high
      school non-completion among women of childbearing age; these factors explained
      31.0% and 5.3% of the attributable increase in maternal mortality during the
      study period, respectively. Among delivering mothers, prevalence of diabetes
      (17.0%), attending fewer than 10 prenatal visits (4.9%), and African American
      race (2.0%) were also associated with higher maternal mortality, as was time
      varying state adoption of the 2003 death certificate (31.1%). CONCLUSIONS: Our
      findings indicate that, in addition to better case ascertainment of maternal
      deaths, adverse changes in chronic diseases, insufficient healthcare access, and
      social determinants of health represent identifiable risks for maternal mortality
      that merit prompt attention in population-directed interventions and health
      policies.

PMID- 30103717
TI  - Electroclinical characteristics of seizures arising from the precuneus based on
      stereoelectroencephalography (SEEG).
AB  - BACKGROUND: Seizures arising from the precuneus are rare, and few studies have
      aimed at characterizing the clinical presentation of such seizures within the
      anatomic context of the frontoparietal circuits. We aimed to characterize the
      electrophysiological properties and clinical features of seizures arising from
      the precuneus based on data from stereoelectroencephalography (SEEG). METHODS:
      The present retrospective study included 10 patients with medically intractable
      epilepsy, all of whom were diagnosed with precuneal epilepsy via
      stereoelectroencephalography (SEEG) at Yuquan Hospital and Xuan Wu Hospital
      between 2014 and 2016. Clinical semiology, scalp electroencephalography (EEG)
      findings, magnetic resonance images (MRI), and positron emission tomography (PET)
      images were analyzed during phase I preoperative evaluations. Following electrode
      implantation, the semiological sequence, ictal SEEG evolution, and anatomy of the
      relevant brain structures were analyzed for each seizure. RESULTS: Seven of ten
      patients reported auras, including body image disturbance (2/7), vestibular
      responses (2/7), somatosensory auras (1/7), visual auras (1/7), and non-specific
      auras (1/7). Primary motor manifestations included bilateral asymmetric tonic
      seizures (BATS) (7/10) and hypermotor seizures (HMS) (3/10). In one patient,
      epileptiform discharge on interictal EEG occurred ipsilateral to the side of the
      epileptogenic zone (EZ). Discharge was non-lateralized in the remaining nine
      patients. In six patients, interictal EEG signals were primarily localized in the
      temporal-parietal-occipital area. In two patients, ictal onset occurred
      ipsilateral to the EZ, which was mainly located in the temporal-parietal
      occipital area. Two patterns of seizure spread were observed. The first pattern
      was characterized by BATS activity with ictal spread to the supplementary motor
      area (SMA), paracentral lobule (PCL), precentral gyrus (PrCG), or postcentral
      gyrus (PoCG). The second pattern was characterized by HMS activity with ictal
      spread to middle cingulate cortex (MCC) and posterior cingulate cortex (PCC).
      CONCLUSION: Aura type (e.g., body image disturbance and vestibular response),
      BATS, and HMS are the main indicators of precuneal epilepsy. Scalp EEG is of
      little use when attempting to localize precuneal seizures. Our findings indicate
      that the clinical characteristics of precuneal epilepsy vary among patients, and
      that the final electro-clinical phenotype depends on the pattern of seizure
      spread.

PMID- 30103718
TI  - Assessing amblyopia treatment using multifocal visual evoked potentials.
AB  - BACKGROUND: To evaluate the effect of occlusion treatment for anisometropic
      amblyopia using multifocal visual evoked potentials (mfVEPs). METHODS: The
      patients for this study comprised 19 patients (mean age 6.05 +/- 1.65 years) with
      anisometropic amblyopia underwent mfVEP analysis using the RETIscan(r) system
      before and after occlusion treatment. After dividing the area into six ring areas
      and four quadrants, we analyzed the amplitudes and latencies of the mfVEPs.
      RESULTS: The amplitudes of ring 1 (central field) in amblyopic eyes after
      treatment were significantly higher than those in the other rings (p = 0.001).
      The mfVEP amplitudes in each of the six rings between amblyopic eyes and fellow
      eyes at diagnosis and after occlusion treatment showed no significant
      differences. In quadrant 1 the amplitudes of the amblyopic eyes and fellow eyes
      were significantly different at the time of diagnosis (p = 0.005), whereas after
      occlusion treatment there was no significant difference (p = 0.888). The
      amplitudes for each of the six rings at diagnosis and after occlusion treatment
      in amblyopic eyes versus fellow eyes showed no significant difference. There were
      also no differences in the amplitudes in each of the four quadrants at the time
      of diagnosis and after occlusion treatment in amblyopic eyes versus fellow eyes.
      No significant difference was found in the comparison of latency values in each
      of the six rings or in each of the four quadrants at diagnosis and after
      occlusion treatment in amblyopic eyes versus their fellow eyes. CONCLUSIONS: The
      amplitudes of quadrant 1 in amblyopic eyes compared with those of the fellow eyes
      at diagnosis were increased after occlusion treatment. Changes of the difference
      between amblyopic eyes and fellow eyes in quadrant 1 after occlusion treatment
      could be a useful, objective method for monitoring improvement in visual acuity.

PMID- 30103719
TI  - Experiences, attitudes, and perceptions of caregivers of individuals with
      treatment-resistant schizophrenia: a qualitative study.
AB  - BACKGROUND: Treatment-resistant schizophrenia (TRS) affects about one-third of
      individuals with schizophrenia. People with TRS do not experience sustained
      symptom relief and at the same time have the most severe disease-related
      disability and associated costs among individuals with severe mental disorders.
      Like caregivers of people with treatment-responsive schizophrenia, caregivers of
      individuals with TRS experience the disease burden along with their care
      recipients; however, for those providing care for individuals with TRS, the
      stress of the burden is unrelenting due to uncontrolled symptoms and a lack of
      effective treatment options. The objective of this study is to better understand
      the burden of TRS from the caregiver perspective and to explore their perception
      of available treatments. METHODS: Eight focus groups with non-professional,
      informal caregivers of individuals with TRS were conducted in 5 US locations. TRS
      was defined as failure of >=2 antipsychotics and persistent moderate-to-severe
      positive symptoms of schizophrenia, per caregiver report. RESULTS: The 27
      caregivers reported an average of 37 h/week providing direct care, and 21
      reported being on call "24/7." Caregivers commonly reported that their care
      recipients exhibited symptoms of auditory hallucinations (89%),
      agitation/irritability/hostility (81%), suspiciousness (78%), tangentiality
      (74%), and cognitive impairment (74%); 70% of caregivers ranked
      suspiciousness/persecution as the most challenging symptom category. Caring for
      an individual with TRS impacted many caregivers' finances, career prospects,
      social relationships, and sense of freedom. Additionally, multiple medication
      failures led to a sense of hopelessness for many caregivers. CONCLUSIONS:
      Persistent positive symptoms caused significant perceived burden, feelings of
      being overwhelmed and having no relief, and substantial negative impacts on
      caregivers' emotional and physical health. To address these substantial unmet
      needs, policy makers should be aware of the need for practical, social, and
      emotional support for these caregivers and their families. Additionally, new
      treatment options for TRS should be developed.

PMID- 30103721
TI  - Epidemiology of birth defects based on surveillance data from 2011-2015 in
      Guangxi, China: comparison across five major ethnic groups.
AB  - BACKGROUND: The causes of birth defects (BDs) are complex and include genetic and
      environmental factors and/or their interactions. More research is needed to
      describe the epidemiology of BDs within specific regions of China. This study
      focused on differences in the prevalence of BDs based on ethnicity in a large
      city in Guangxi Province, China. METHODS: Surveillance data of infants born in
      114 registered hospitals in Liuzhou between 2011 and 2015 were analyzed to
      determine the epidemiology of BDs across five major ethnic groups. We calculated
      the prevalence of BDs and relative risk of BDs by ethnicity. RESULTS: There were
      260,722 perinatal infants of which 6581 had BDs, with the average prevalence of
      25.24 per 1000 perinatal infants (PIs). Prevalence data showed an obvious uptrend
      over the past 5 years. Han had the highest prevalence of total BDs (28.980/00),
      followed by Zhuang (25.190/00), Yao (18.500/00), Miao (15.780/00) and Dong
      (14.240/00). Relative to the Han; Zhuang, Miao, Yao, and Dong had a lower risk of
      musculoskeletal and urogenital malformations; Miao and Yao had a lower risk of
      cardiovascular malformation; and Dong had a lower risk of cardiovascular and
      craniofacial malformation. Several maternal risk factors were found to be
      associated with BDs (e.g., maternal and gestational age, number of antenatal care
      visits). CONCLUSION: This study provided a comprehensive description of ethnic
      differences in the risk of BDs in Liuzhou City, China. Observed ethnic
      differences in the risk of BDs may be related to genetic susceptibilities,
      environment, cultural customs, or to potential combinations of these factors.

PMID- 30103722
TI  - An assessment of the use of complementary and alternative medicine by Korean
      people using an adapted version of the standardized international questionnaire
      (I-CAM-QK): a cross-sectional study of an internet survey.
AB  - BACKGROUND: In Korea, there are two types of medical doctors: one practises
      conventional medicine (hereafter called a physician), and the other practises
      traditional medicine (hereafter called a Korean medical doctor). This study aimed
      to compare the provision of complementary and alternative medicine (CAM) by these
      providers to CAM use per self-judgement in Korea. METHODS: We analysed 1668
      Korean people via an internet survey with the Korean adopted version of the I-CAM
      Q, namely, the International Questionnaire to measure use of CAM, to understand
      whether respondents used CAM based either on a prescription or advice from a
      physician or a Korean medical doctor or on self-judgement. RESULTS: In the
      previous 12 months, the proportions of respondents who were treated by a
      physician, who were treated by a Korean medical doctor and who were not treated
      by anyone were 67.9, 20.7 and 14.2%, respectively. Among the respondents who
      received CAM based on a prescription or advice from a physician, traditional
      Korean medicine practices and dietary supplements were commonly used; only a
      small percentage used other CAM therapies. Respondents who received CAM based on
      a prescription or advice from a Korean medical doctor showed similar results.
      Acupuncture and moxibustion, traditional Korean medicines (decoction), or cupping
      were more commonly used. Korean traditional medicines as over-the-counter (OTC)
      drugs were more commonly used by respondents who received CAM therapy based on a
      prescription or advice from a physician than by those who received CAM therapy
      based on a prescription or advice from a Korean medical doctor. A total of 74% of
      the responders used any CAM by self-judgement in the previous 12 months.
      CONCLUSIONS: For the use of CAM in Korea, in addition to the Korean traditional
      medical care provided by Korean medical doctors, general physicians advised
      people regarding Korean traditional medical care and dietary supplements.

PMID- 30103720
TI  - Relevant prognostic factors influencing outcome of patients after surgical
      resection of distal cholangiocarcinoma.
AB  - BACKGROUND: Distal cholangiocarcinoma (DCC) is a rare but over the last decade
      increasing malignancy and is associated with poor prognosis. According to the
      present knowledge curative surgery is the only chance for long term survival.
      This study was performed to evaluate prognostic factors for the outcome of
      patients undergoing curative surgery for distal cholangiocarcinoma. METHODS: 75
      patients who underwent surgery between January 2000 and December 2014 for DCC in
      curative intention were analysed retrospectively. Potential prognostic factors
      for survival were investigated including the extent of surgery using purposeful
      selection of covariates in multivariable Cox regression modeling. RESULTS:
      Preoperative biliary stenting (Hazard ratio (HR): 2.530; 95%-CI: 1.146-6.464, p =
      0.020), the extent of surgery in case of positive histological venous invasion
      (HR: 1.209; 95%-CI: 1.017-1.410, p = 0.032), lymph node staging (HR: 2.183; 95%
      CI: 1.250-3.841, p = 0.006), perineural invasion (HR: 2.118; 95%-CI: 1.147-4.054,
      p = 0.016) and postoperative complications graded in points according to Clavien
      Dindo (HR: 1.395; 95%-CI: 1.148-1.699, p = 0.001) were indentified as independent
      significant risk factors for survival. Patients receiving preoperative biliary
      stenting showed prolonged duration between onset of symptoms and date of
      operation (p = 0.048). CONCLUSIONS: Preoperative biliary stenting reduces
      survival possibly due to delayed surgery. The extent of surgery is not an
      independent risk factor for survival except for patients with concomitant
      histological venous invasion. Oncological factors and postoperative surgical
      complications are independent prognostic factors for survival.

PMID- 30103723
TI  - Correction to: Complex multiple risk intervention to promote healthy behaviours
      in people between 45 to 75 years attended in primary health care (EIRA study):
      study protocol for a hybrid trial.
AB  - It has been highlighted the original article (1) contained a typesetting mistake
      in the authorship, and that author Caterine Vicens was omitted.

PMID- 30103724
TI  - The efficacy of platelet-rich fibrin as a scaffold in regenerative endodontic
      treatment: a retrospective controlled cohort study.
AB  - BACKGROUND: Blood Clot (BC) or platelet concentrates have been used as scaffold
      in regenerative endodontic treatment (RET). The aim of this retrospective study
      was to compare the performance of platelet-rich fibrin (PRF) with BC in inducing
      root development and periapical lesion healing after tooth revascularization.
      METHODS: Five patients receiving RET using PRF as a scaffold were matched 1:1 to
      a previous cohort of 5 patients who underwent tooth revascularization by
      provoking periapical bleeding. Clinical signs and symptoms were examined at
      follow-ups. Periapical lesion healing and root development were monitored
      radiographically. The resolution of clinical signs and symptoms as well as
      periapical radiolucency was observed in all patients (100%). RESULTS: Root
      elongation, dentinal wall thickening and apex closure were found in most cases
      (80% in both groups). There was no significant difference between the groups in
      terms of clinical sign resolution, root development and periapical healing.
      CONCLUSIONS: Within the limits of this study, PRF achieved comparable outcomes to
      BC in terms of clinical sign and symptom resolution, periapical lesion healing
      and continued root development in RET.

PMID- 30103725
TI  - Incidence and prevalence of neuroendocrine tumors of the lung: analysis of a US
      commercial insurance claims database.
AB  - BACKGROUND: As reported in Surveillance, Epidemiology, and End Results (SEER)
      data, US incidence and prevalence of neuroendocrine tumors (NET) has increased
      over recent years. The study objective was to update incidence and prevalence
      information for lung NET using administrative claims. METHODS: This descriptive
      epidemiological study used 2009-2014 data from 2 US claims databases: MarketScan
      and PharMetrics. Patients (18-64 years old) had >=1 inpatient or >= 2 outpatient
      claims with NET of bronchus or lung, identified by International Classification
      of Diseases, 9th Revision, Clinical Modification diagnosis codes. Prevalence was
      number of lung NET patients divided by number of enrollees/year. Incidence was
      number of patients with a first observed NET diagnosis who were disease-free for
      2 years prior, divided by number of enrollees. Age and gender adjustments
      performed. RESULTS: The annual number of patients with lung NET identified from
      2009 to 2014 ranged from 435 to 796 (MarketScan) and 419-648 (PharMetrics). In
      MarketScan, there was a 7.4% (95%CI 2.1-13.0; p = 0.027) annual percent change
      (APC) in the age-adjusted incidence for males and 6.8% (- 0.2-14.3; 0.052) for
      females. In PharMetrics, APC was - 2.9% (- 13.8-9.4; 0.395) for males; 14.7% (-
      12.9-51.2; 0.165) for females. In MarketScan, APC in age-adjusted prevalence for
      males was 9.9% (4.7-15.3; 0.006); 16.2% (11.4-21.1; <.001) for females. For
      PharMetrics, APCs were 9.5% (2.3-17.2; 0.021) for males; 16.3% (9.6-23.5; 0.002)
      for females. CONCLUSIONS: From 2009 to 2014 there was a statistically significant
      increase in age-adjusted lung NET incidence for males in MarketScan, and a
      statistically significant increase in age-adjusted prevalence for both genders in
      PharMetrics. Incidence and prevalence changes, to the extent they exist, may be
      due to better diagnostic methods, increased awareness of NET among clinicians and
      pathologists, and/or an actual increase in US disease occurrence. Differences in
      rates across databases are difficult to explain. These results suggest the need
      for awareness of the clinically effective and safe treatment options available
      for lung NET patients among healthcare providers.

PMID- 30103726
TI  - Services according to mental health needs for youth in foster care? - A multi
      informant study.
AB  - BACKGROUND: Foster children have a high risk of mental disorders. This has
      contributed to increased international attention to service utilization for youth
      in foster care. The aim of this study is to examine whether youth in foster care
      receive services according to need, by using a multi-informant design. METHOD:
      Detailed information on the type and frequency of service use during the last 2
      years and on youth mental health were collected from foster youths and their
      carers in Norway (n = 405, aged 11-17 years) through online questionnaires.
      Mental health was assessed with the Strengths and Difficulties Questionnaire.
      Statistical analyses were conducted using descriptive statistics and log
      binominal regressions. RESULTS: In total, 48.8% of foster youths showed evidence
      of mental health problems, and 74.5% of foster families had contact with
      services. Increased mental health problems and living in non-kin foster care were
      associated with more service use. Youths with mental health problems had twice
      the probability of receiving services from the child and adolescent mental health
      service (CAMHS) and primary health care services compared to youths without
      problems. However, 57.0% of youths with carer-reported mental health problems did
      not have contact with CAMHS. CONCLUSIONS: Service use among foster youths was
      associated with service need rather than demographic and placement
      characteristics. The majority of youths with mental health problems did not
      receive services from CAMHS. However, many of them were in contact with primary
      health care services.

PMID- 30103727
TI  - Radial probe endobronchial ultrasound using a guide sheath for peripheral lung
      lesions in beginners.
AB  - BACKGROUND: The diagnostic yields and safety profiles of transbronchial lung
      biopsy have not been evaluated in inexperienced physicians using the combined
      modality of radial probe endobronchial ultrasound and a guide sheath (EBUS-GS).
      This study assessed the utility and safety of EBUS-GS during the learning phase
      by referring to a database of performed EBUS-GS procedures. METHODS: From
      December 2015 to January 2017, all of the consecutive patients who underwent EBUS
      GS were registered. During the study period, two physicians with no previous
      experience performed the procedure. To assess the diagnostic yields, learning
      curve, and safety profile of EBUS-GS performed by these inexperienced physicians,
      the first 100 consecutive EBUS-GS procedures were included in the evaluation.
      RESULTS: The overall diagnostic yield of EBUS-GS performed by two physicans in
      200 patients with a peripheral lung lesion was 73.0%. Learning curve analyses
      showed that the diagnostic yields were stable, even when the procedure was
      performed by beginners. Complications related to EBUS-GS occurred in three
      patients (1.5%): pneumothorax developed in two patients (1%) and resolved
      spontaneously without chest tube drainage; another patient (0.5%) developed a
      pulmonary infection after EBUS-GS. There were no cases of pneumothorax requiring
      chest tube drainage, severe hemorrhage, respiratory failure, premature
      termination of the procedure, or procedure-related mortality. CONCLUSIONS: EBUS
      GS is a safe and stable procedure with an acceptable diagnostic yield, even when
      performed by physicians with no previous experience.

PMID- 30103728
TI  - How adverse childhood experiences relate to single and multiple health risk
      behaviours in German public university students: a cross-sectional analysis.
AB  - BACKGROUND: Adverse childhood experiences (ACEs) have been shown to be linked to
      health risk behaviours (HRBs). This study aims to identify risk factors for ACEs
      and to examine the associations between ACEs and single and multiple HRBs in a
      sample of university students in Germany. METHODS: An online-based cross
      sectional study was conducted among public university students (N = 1466). The
      widely applied ACE questionnaire was used and extended to operationalise 13
      categories of childhood adversity. First, variables for each type of ACE and HRB
      were dichotomised (single ACEs and single HRBs), and then used for cumulative
      scores (multiple ACEs and multiple HRBs). Frequencies were assessed, and
      (multinomial) logistic regression analyses were performed. RESULTS: Prevalence
      rates of ACEs ranged from 3.9 to 34.0%, depending on the type of childhood
      adversity. Sociodemographic risk and protective factors for single/multiple ACEs
      varied strongly depending on the outcome. In particular, a high family
      socioeconomic status seemed to be a consistent protective factor for most ACEs.
      After adjusting for sociodemographic characteristics, both single and multiple
      HRBs were associated with single events of ACEs. Moreover, dose-response
      relationships between multiple ACEs and various single and multiple HRBs were
      found. CONCLUSIONS: The study provides strong evidence that ACEs are associated
      with HRBs. The number of ACEs may play a role in single or multiple HRBs.
      Reducing the number of ACEs could thus decrease HRBs, which account for many of
      the leading causes of morbidity and death. The findings highlight the importance
      of trauma-informed health interventions designed to prevent the occurrence of
      ACEs, and build capacity among children and adults.

PMID- 30103729
TI  - A suppressive role of guanine nucleotide-binding protein subunit beta-4 inhibited
      by DNA methylation in the growth of anti-estrogen resistant breast cancer cells.
AB  - BACKGROUND: Breast cancer is the most common malignancy in women worldwide.
      Although the endocrine therapy that targets estrogen receptor alpha (ERalpha)
      signaling has been well established as an effective adjuvant treatment for
      patients with ERalpha-positive breast cancers, long-term exposure may eventually
      lead to the development of acquired resistance to the anti-estrogen drugs, such
      as fulvestrant and tamoxifen. A better understanding of the mechanisms underlying
      antiestrogen resistance and identification of the key molecules involved may help
      in overcoming antiestrogen resistance in breast cancer. METHODS: The whole-genome
      gene expression and DNA methylation profilings were performed using fulvestrant
      resistant cell line 182R-6 and tamoxifen-resistant cell line TAMR-1 as a model
      system. In addition, qRT-PCR and Western blot analysis were performed to
      determine the levels of mRNA and protein molecules. MTT, apoptosis and cell cycle
      analyses were performed to examine the effect of either guanine nucleotide
      binding protein beta-4 (GNB4) overexpression or knockdown on cell proliferation,
      apoptosis and cell cycle. RESULTS: Among 9 candidate genes, GNB4 was identified
      and validated by qRT-PCR as a potential target silenced by DNA methylation via
      DNA methyltransferase 3B (DNMT3B). We generated stable 182R-6 and TAMR-1 cell
      lines that are constantly expressing GNB4 and determined the effect of the
      ectopic GNB4 on cell proliferation, cell cycle, and apoptosis of the antiestrogen
      resistant cells in response to either fulvestrant or tamoxifen. Ectopic
      expression of GNB4 in two antiestrogen resistant cell lines significantly
      promoted cell growth and shortened cell cycle in the presence of either
      fulvestrant or tamoxifen. The ectopic GNB4 induced apoptosis in 182R-6 cells,
      whereas it inhibited apoptosis in TAMR-1 cells. Many regulators controlling cell
      cycle and apoptosis were aberrantly expressed in two resistant cell lines in
      response to the enforced GNB4 expression, which may contribute to GNB4-mediated
      biologic and/or pathologic processes. Furthermore, knockdown of GNB4 decreased
      growth of both antiestrogen resistant and sensitive breast cancer cells.
      CONCLUSION: GNB4 is important for growth of breast cancer cells and a potential
      target for treatment.

PMID- 30103730
TI  - Diagnostic value of cardiopulmonary ultrasound in elderly patients with acute
      respiratory distress syndrome.
AB  - BACKGROUND: Lung ultrasound and echocardiography are mainly applied in critical
      care and emergency medicine. However, the diagnostic value of cardiopulmonary
      ultrasound in elderly patients with acute respiratory distress syndrome (ARDS) is
      still unclear. METHODS: Consecutive patients admitted to ICU with the diagnosis
      of suspected ARDS based on clinical grounds were enrolled. Cardiopulmonary
      ultrasound was performed as part of monitoring on day 1, day 2 and day 3. On each
      day a bedside ultrasound was performed to examine the lungs and calculate the
      Left Ventricular Ejection Fraction (LVEF). On day 3, a thoracic CT was performed
      on each patient as gold standard for ARDS imaging diagnosis. According to the
      results from CT scan, patients were grouped into ARDS group or Non-ARDS group.
      The relation between the cardiopulmonary ultrasound results on each day and the
      results of CT scan was analyzed. RESULTS: Fifty one consecutive patients aged
      from 73 to 97 years old were enrolled. Based on CT criteria, 33 patients were
      classified into the ARDS group, while 18 patients were included in non-ARDS
      group. There was no significant difference between the two groups in baseline
      characteristics, including gender, age, underlying disease, comorbidities, APACHE
      II score, SOFA score, and PaO2/FiO2 ratio (P > 0.05). Lung ultrasound (LUS)
      examination results were consistent with the CT scan results in diagnosis of
      pulmonary lesions. The Kappa values were 0.55, 0.74 and 0.82 on day 1, day 2 and
      day 3, respectively. The ROC analysis showed that the sensitivity, specificity
      and area under curve of ROC (AUROC) for lung ultrasound in diagnose ARDS were
      0.788,0.778,0.783;0.909,0.833,0.871;0.970,0.833,0.902 on day 1, day 2 and day 3,
      respectively. However, cardiopulmonary ultrasound performed better in diagnosing
      ARDS in elderly patients. The sensitivity, specificity and AUROC were
      0.879,0.889,0.924;0.939,0.889,0.961;and 0.970,0.833,0.956 on day 1, day 2 and day
      3, respectively. The combined performances of cardiopulmonary ultrasound, N
      terminal pro-brain natriuretic peptide (NT-proBNP), and PaO2/FiO2 ratio improved
      the specificity of the diagnosis of ARDS in elderly patients. CONCLUSIONS: LUS
      examination results were consistent with the CT scan results in diagnosis of
      pulmonary lesions. Cardiopulmonary ultrasound has a greater diagnostic accuracy
      in elderly patients with ARDS, compared with LUS alone. The combined performances
      of cardiopulmonary ultrasound, NT-proBNP, and PaO2/FiO2 increased the specificity
      of the diagnosis of ARDS in elderly patients.

PMID- 30103731
TI  - Dignity and respect during pregnancy and childbirth: a survey of the experience
      of disabled women.
AB  - BACKGROUND: Despite the increasing number of women with disability globally
      becoming pregnant, there is currently limited research about their experiences. A
      national survey of women's experience of dignity and respect during pregnancy and
      childbirth raised concerns about the possibility of women with disability having
      unequal care with overall less choice and control. To address this further we
      conducted a study to explore the experiences of dignity and respect in childbirth
      of women with disability. METHODS: The study involved a self-selecting,
      convenience sample of 37 women who had given birth in the United Kingdom and
      Ireland and had completed an internet-based survey. Women were identified through
      online networks and groups of and for disabled parents and for people with
      specific medical conditions. Data were collected using an online survey tool.
      Survey data were analysed using descriptive statistics. Thematic analysis was
      used for open questions. RESULTS: Despite generally positive responses, just over
      half of the group of women expressed dissatisfaction with care provision. Only
      19% thought that reasonable adjustments or accommodations had been made for them
      (7/37). When reasonable adjustments were not in place, participants' independence
      and dignity were undermined. More than a quarter of women felt they were treated
      less favourably because of their disability (10/37, 27%). At all points in the
      pregnancy continuum more than a quarter of women felt their rights were either
      poorly or very poorly respected; however this was greatest in the postnatal
      period (11/35, 31%). In addition, more than half of the women (20/36, 56%) felt
      that maternity care providers did not have appropriate awareness of or attitudes
      to disability. CONCLUSIONS: Women's experiences of dignity and respect in
      childbirth revealed that a significant proportion of women felt their rights were
      poorly respected and that they were treated less favourably because of their
      disability. This suggests that there is a need to look more closely at
      individualised care. It was also evident that more consideration is required to
      improve attitudes of maternity care providers to disability and services need to
      adapt to provide reasonable adjustments to accommodate disability, including
      improving continuity of carer.

PMID- 30103732
TI  - Effects of midwife-led maternity services on postpartum wellbeing and clinical
      outcomes in primiparous women under China's one-child policy.
AB  - BACKGROUND: The Midwife-led maternity services have been implemented in China in
      response to the high rates of primiparous women and Caesarean Sections (CS) which
      may be related to China's one-child policy. However, few studies in China have
      been reported on the effectiveness of Midwife-led Care at Delivery (MCD) and the
      Continuity of Midwife-led Care (CMC) on postpartum wellbeing and other clinical
      outcomes. Therefore, evidence-based clinical validation is needed to develop an
      optimal maternity service for childbearing women in China. METHODS: A concurrent
      cohort study design was conducted with 1730 pregnant women recruited from 9
      hospitals in Shanghai. Among the 1730 participants at baseline, 1568 participants
      completed the follow-up questionnaire, with a follow-up rate of 90.6%. RESULTS:
      Compared with the routine Obstetrician-led Maternity Care (OMC), Midwife-led Care
      at Delivery (MCD) was associated with CS rate (OR were 0.16; 95%CI: 0.11 to 0.25)
      and a higher total score of postpartum wellbeing (betawere 2.70; 95%CI: 0.70 to
      4.70) when adjusting for the baseline differences and other confounders during
      delivery or postpartum period. Moreover, continuity of Midwife-led Care (CMC) was
      associated with CS rate (OR were 0.30; 95%CI: 0.23 to 0.41), as well as increased
      rate of breastfeeding within the first 24 h (OR were 2.49; 95% CI: 1.47 to 4.23),
      higher postpartum satisfaction (beta = 4.52; 95% CI: 1.60 to 12.68), lower
      anxiety (betawere 0.66; 95% CI: 0.16 to 1.17), increased self-control (betawere
      0.39; 95% CI: 0.02 to 0.76) and a higher total score of postpartum wellbeing
      (betawere 3.14; 95% CI: 1.54 to 4.75). CONCLUSION: CMC is the optimal service for
      low-risk primiparous women under China's one-child policy, and is worthwhile for
      a general implementation across China.

PMID- 30103734
TI  - A multi-centre quality improvement project to reduce the incidence of obstetric
      anal sphincter injury (OASI): study protocol.
AB  - BACKGROUND: Third and fourth degree perineal tears, or obstetric anal sphincter
      injuries (OASI), sustained during childbirth can result in anal incontinence and
      psychosocial problems which require ongoing treatment. Within the English
      National Health System (NHS) reported rates of OASI have gradually increased. In
      response, a care bundle was developed incorporating four elements: 1) antenatal
      information to women, 2) manual perineal protection during all vaginal births, 3)
      episiotomy to be performed with a 60 degrees  mediolateral angle at crowning
      (when clinically indicated) and 4) perineal examination (including per rectum)
      after childbirth. Implementation of the OASI Care Bundle is aided by a skills
      development module and an awareness campaign. The project is a collaboration
      between two national professional bodies, an NHS hospital trust and an academic
      institution. METHODS: Implementation of the OASI Care Bundle will be evaluated
      using a stepped-wedge design. From January 2017 sixteen maternity units across
      England, Wales and Scotland will participate in the study over a 15-month period,
      with sequential roll-out of the intervention in four blocks (regions) of four
      units. The primary clinical outcome is OASI rate. Regression analysis will adjust
      for differences in organisational characteristics and obstetric risk factors in
      women who gave birth before and after implementation of the care bundle. Focus
      group discussions and in-depth interviews with clinicians will evaluate the
      feasibility of integrating the care bundle into routine practice. Interviews with
      women will explore the acceptability of the intervention. DISCUSSION: This
      protocol outlines the evaluation of our quality improvement project which aims to
      prevent OASI using a bundle of evidence-based interventions that are each widely
      used in practice. The OASI project aims to 1) standardise practice to prevent
      OASI in a way that is acceptable to clinicians and women and 2) identify the
      barriers and enablers associated with upscaling interventions within maternity
      units. If found to be effective, feasible and acceptable, the OASI Care Bundle
      will be shared with a range of audiences using the communication channels
      available to the professional bodies. TRIAL REGISTRATION: The OASI Project was
      retrospectively registered on the ISCTRN12143325 database date assigned
      03/10/2017.

PMID- 30103733
TI  - Early increase in blood supply (EIBS) is associated with tumor risk in the
      Azoxymethane model of colon cancer.
AB  - BACKGROUND: The present study aimed to investigate the role of blood supply in
      early tumorigenesis in colorectal cancer. We leveraged the renin angiotensin
      system (RAS) to alter colonic blood supply and determine the effect on tumor
      initiation and progression. METHODS: To test the effect of blood supply on
      tumorigenesis, 53 male A/J mice were randomly assigned to one of three RAS
      modulation groups and one of two AOM treatments. The RAS modulation groups were
      I) water (RAS-unmodulated) as a control group, II) angiotensin-II and III) the
      angiotensin receptor blocker, Losartan. The mice in each group were then randomly
      split into either the saline control condition or the AOM-treated condition in
      which tumors were induced with a standard protocol of serial azoxymethane (AOM)
      injections. To monitor microvascular changes in the rectal mucosa during the
      study, we used confocal laser endomicroscopy (CLE) with FITC-Dextran for in-vivo
      imaging of vessels and polarization-gated spectroscopy (PGS) to quantify rectal
      hemoglobin concentration ([Hb]) and blood vessel radius (BVR). RESULTS: At 12
      weeks post-AOM injections and before tumor formation, CLE images revealed many
      traditional hallmarks of angiogenesis including vessel dilation, loss of co
      planarity, irregularity, and vessel sprouting in the pericryptal capillaries of
      the rectal mucosa in AOM-Water tumor bearing mice. PGS measurements at the same
      time-point showed increased rectal [Hb] and decreased BVR. At later time points,
      CLE images showed pronounced angiogenic features including irregular networks
      throughout the colon. Notably, the AOM-Losartan mice had significantly lower
      tumor multiplicity and did not exhibit the same angiogenic features observed with
      CLE, or the increase in [Hb] or decrease in BVR measured with PGS. The AOM-AngII
      mice did not have any significant trends. CONCLUSION: In-vivo PGS measurements of
      rectal colonic blood supply as well as CLE imaging revealed angiogenic
      disruptions to the capillary network prior to tumor formation. Losartan
      demonstrated an effective way to mitigate the changes to blood supply during
      tumorigenesis and reduce tumor multiplicity. These effects can be used in future
      studies to understand the early vessel changes observed.

PMID- 30103735
TI  - Fortified food supplementation in children with reduced dietary energy and
      micronutrients intake in Southern Mexico.
AB  - BACKGROUND: Nutritional supplements are an important source of complementary food
      for young children, since they may either complement or substitute nutrients
      obtained from other food sources. Assessing how the introduction of different
      types of supplements modifies the consumption of other food sources may help in
      designing supplementation programs that aim to improve the nutrition of
      vulnerable populations. The objetive is to quantify dietary energy and nutrient
      intake among children aged 6-12 months who received one of three nutritional
      supplements. METHODS: A cluster-randomized trial was conducted from 2005 to 2007.
      Urban communities were randomly allocated to one of three intervention groups
      receiving one of the following: a milk-based fortified food, micronutrient
      powders, or syrup. Each supplement was fortified with equal amounts of
      micronutrients. Dietary intake was estimated using a food frequency questionnaire
      (FFQ) to reflect the average consumption over the month prior to the interview.
      Children between 6 and 12 months of age were recruited. Median regression was
      performed with adjusted standard errors for clustered data, and the linear
      predictors for the median included the study group, study stage and their
      interaction. Adjusted medians by study group and study stage were obtained as
      post-estimations. RESULTS: No statistically significant differences between study
      groups were observed at baseline. After four months of supplementation, the
      children in the fortified food group had a smaller increase in median dietary
      energy (183.7 kcal, CI95%: 59.9, 307.5) and dietary protein (6.6 g, CI95%: 2.6,
      10.6) intake from their home diet than those in the syrup group (p < 0.05). These
      differences remained significant after adjusting for group differences at
      baseline. Regarding covariate-adjusted median changes from baseline to follow-up
      at 10 months, the children in the fortified food group had a smaller median
      increase in dietary energy intake than those in the syrup group (698 vs 915
      kcal), with a difference of 217.9 kcal (CI95%: 20.4, 415.4). CONCLUSION: Children
      in the fortified food group consumed less dietary energy, protein, and
      micronutrients than those in the micronutrient powder and syrup groups. It is
      possible that absolute nutrient intake may be overestimated by the FFQ, but this
      possibility does not compromise the ability to compare study groups. Given the
      observed differences in dietary energy consumption among the three supplemented
      groups, it can be concluded that supplementation with micronutrient powders is an
      adequate option for urban children who have met their minimum energy and protein
      requirements.

PMID- 30103736
TI  - Effectiveness evaluation of quota payment for specific diseases under global
      budget: a typical provider payment system reform in rural China.
AB  - BACKGROUND: Quota payment for specific diseases under global budget is one of the
      most typical modes of provider payment system reform in rural China. This study
      aimed to assess this reform mode from aspects of the total fee, structure of the
      fee and enrollees' benefits. METHODS: A total of 127,491 inpatient records from
      2014 to 2016 were extracted from the New Rural Cooperative Medical Scheme (NRCMS)
      database in Weiyuan County, Gansu Province. Total fee, actual compensation ratio,
      out-of-pocket ratio, constituent ratio of the treatment fee, constituent ratio of
      the inspection and laboratory fee, and length of stay were selected as dependent
      variables. Both generalized additive models (GAMs) and multiple linear regression
      models were used to measure the change in dependent variables along with year.
      RESULTS: Prior to the adjustment of the compensation type, out-of-pocket ratio
      and length of stay decreased, while total fee, actual compensation ratio,
      constituent ratio of the treatment fee, and constituent ratio of the inspection
      and laboratory fee increased. After the compensation type was adjusted, the mean
      of the total fee increased rapidly in 2015 and remained stable in 2016. The mean
      length of stay increased in 2015 but decreased in 2016. A comparison of
      inpatients suffering from diseases covered by quota payments and those suffering
      from general diseases revealed that total fee, out-of-pocket ratio, and length of
      stay decreased and actual compensation ratio increased for the former, whereas
      the opposite was true for the latter. Constituent ratio of the treatment fee and
      constituent ratio of the inspection and laboratory fee increased for both
      samples, except for the constituent ratio of the inspection and laboratory fee of
      quota payment diseases in 2016, which did not change. CONCLUSIONS: Quota payment
      for specific diseases under global budget had obviously positive effects on cost
      control in Weiyuan, Gansu. Considering the limited coverage of quota payment for
      diseases, the long-term effect of this reform mode and its replicability awaits
      further evaluation.

PMID- 30103739
TI  - Splenic malignant fibrous histiocytoma with concurrent hypertension and epistaxis
      in an Alaskan malamute dog.
AB  - BACKGROUND: Malignant fibrous histiocytoma has been uncommonly described in dogs.
      Several extranasal neoplasias have been reported to result hypertensive
      epistaxis. There are, however, no published case reports of extranasal malignant
      fibrous histiocytoma with concurrent hypertension and epistaxis in dogs. CASE
      PRESENTATION: A 10-year-old dog presented with a spontaneous massive epistaxis
      persisting for 5 days. The dog exhibited unstable hypertension, which was
      considered as a cause of epistaxis. The complete blood count, prothrombin time,
      and activated partial thromboplastin time were within the reference limits, and
      other systemic examination showed no abnormalities except for a splenic mass
      occupying more than one third of the abdomen. Histologic examination of the
      resected spleen revealed the characteristic features of a malignant fibrous
      histiocytoma. One week after splenectomy, the hypertension and epistaxis resolved
      clinically and did not recur on the 5-month follow-up. CONCLUSIONS: The dog's
      blood pressure and epistaxis normalized after malignant fibrous histiocytoma
      resection suggesting that hypertensive epistaxis may be a rare manifestation of
      canine malignant fibrous histiocytoma.

PMID- 30103738
TI  - Study protocol: a cluster randomized controlled trial of web-based decision
      support tools for increasing BRCA1/2 genetic counseling referral in primary care.
AB  - BACKGROUND: BRCA1 and BRCA2 mutations confer a substantial breast risk of
      developing breast cancer to those who carry them. For this reason, the United
      States Preventative Services Task Force (USPSTF) has recommended that all women
      be screened in the primary care setting for a family history indicative of a
      mutation, and women with strong family histories of breast or ovarian cancer be
      referred to genetic counseling. However, few high-risk women are being routinely
      screened and fewer are referred to genetic counseling. To address this need we
      have developed two decision support tools that are integrated into clinical care.
      METHOD: This study is a cluster randomized controlled trial of high-risk patients
      and their health care providers. Patient-provider dyads will be randomized to
      receive either standard education that is supplemented with the patient-facing
      decision aid, RealRisks, and the provider-facing Breast Cancer Risk Navigation
      Toolbox (BNAV) or standard education alone. We will assess these tools'
      effectiveness in promoting genetic counseling uptake and informed and shared
      decision making about genetic testing. DISCUSSION: If found to be effective,
      these tools can help integrate genomic risk assessment into primary care and,
      ultimately, help expand access to risk-appropriate breast cancer prevention
      options to a broader population of high-risk women. TRIAL REGISTRATION: This
      trial is retrospectively registered with ClinicalTrials.gov Identifier:
      NCT03470402 : 20 March 2018.

PMID- 30103737
TI  - Augmented expression of Ki-67 is correlated with clinicopathological
      characteristics and prognosis for lung cancer patients: an up-dated systematic
      review and meta-analysis with 108 studies and 14,732 patients.
AB  - BACKGROUND: Lung cancer ranks as the leading cause of cancer-related deaths
      worldwide and we performed this meta-analysis to investigate eligible studies and
      determine the prognostic effect of Ki-67. METHODS: In total, 108 studies in 95
      articles with 14,732 patients were found to be eligible, of which 96 studies
      reported on overall survival (OS) and 19 studies reported on disease-free
      survival (DFS) with relation to Ki-67 expression in lung cancer patients.
      RESULTS: The pooled hazard ratio (HR) indicated that a high Ki-67 level could be
      a valuable prognostic factor for lung cancer (HR = 1.122 for OS, P < 0.001 and HR
      = 1.894 for DFS, P < 0.001). Subsequently, the results revealed that a high Ki-67
      level was significantly associated with clinical parameters of lung cancer
      including age (odd ratio, OR = 1.246 for older patients, P = 0.018), gender (OR =
      1.874 for males, P < 0.001) and smoking status (OR = 3.087 for smokers, P <
      0.001). Additionally, significant positive correlations were found between Ki-67
      overexpression and poorer differentiation (OR = 1.993, P = 0.003), larger tumor
      size (OR = 1.436, P = 0.003), and higher pathologic stages (OR = 1.867 for III
      IV, P < 0.001). Furthermore, high expression of Ki-67 was found to be a valuable
      predictive factor for lymph node metastasis positive (OR = 1.653, P < 0.001) and
      advanced TNM stages (OR = 1.497 for stage III-IV, P = 0.024). Finally, no
      publication bias was detected in any of the analyses. CONCLUSIONS: This study
      highlights that the high expression of Ki-67 is clinically relevant in terms of
      the prognostic and clinicopathological characteristics for lung cancer.
      Nevertheless, more prospective well-designed studies are warranted to validate
      these findings.

PMID- 30103740
TI  - Real world evaluation of a novel lateral flow assay (AlphaKit(r) QuickScreen) for
      the detection of alpha-1-antitrypsin deficiency.
AB  - BACKGROUND: Alpha-1-Antitrypsin (AAT) deficiency (AATD) is a hereditary disorder
      that manifests primarily as pulmonary emphysema and liver cirrhosis. The
      clinically most relevant mutation causing AATD is a single nucleotide
      polymorphism Glu342Lys (Z-mutation). Despite the recommendation to test every
      COPD patient, the condition remains severely underdiagnosed with a delay of
      several years between first symptoms and diagnosis. The Grifols' AlphaKit(r)
      QuickScreen is a novel qualitative point-of-care (POC) in vitro screening test
      developed for the detection of the Z AAT protein in capillary whole blood. The
      objective of this prospective, international, multi-center, diagnostic,
      interventional real-world study was to assess the performance of this device for
      the detection of AATD in test-naive COPD patients. METHODS: 1044 test-naive COPD
      patients were recruited from 9 centers in Spain and 10 centers in Germany,
      ranging from primary to tertiary care. To evaluate the performance of the test,
      sensitivity, specificity, positive predictive value (PPV), and negative
      predictive value (NPV) were calculated compared with the gold standard
      (genotyping). RESULTS: Genotyping and phenotyping of all 1019 evaluable samples
      revealed 4.12% of patients as carriers of at least one Z-allele, while 0.29%
      carried the homozygous genotype Pi*ZZ. The evaluation of the test's ability to
      detect the PiZ protein yielded the following results: specificity 97.8%,
      sensitivity 73.8%, negative predictive value 98.9%, and positive predictive value
      58.5%. All false negatives (n = 11) were heterozygote Pi*MZ samples. CONCLUSIONS:
      The tested device can be used as an appropriate tool to exclude AATD in primary
      care and in the overall COPD population, except in patients with a high a-priori-
      probability of AATD.

PMID- 30103741
TI  - Serum hepatokines in dairy cows: periparturient variation and changes in energy
      related metabolic disorders.
AB  - BACKGROUND: During peripartum period, dairy cows are highly susceptible to energy
      metabolism disorders such as fatty liver and ketosis. Angiopoietin-like protein 4
      (ANGPTL4) and fibroblast growth factor 21 (FGF21), known as hepatokines, play
      important roles in lipid metabolism. The purposes of our study were to evaluate
      variations of serum ANGPTL4 and FGF21 concentrations in periparturient dairy cows
      and changes in these serum analyte concentrations of energy-related metabolic
      disorders in early lactation dairy cows. This study was divided into two
      experiments. Experiment I: Blood parameters were measured in healthy
      periparturient Holstein cows from 4 wk antepartum to 4 wk postpartum (n = 219).
      In this experiment, weekly blood samples were obtained from 4 wk before the
      expected calving date through 4 wk after calving. Experiment II: Blood parameters
      were measured in healthy cows (n = 30) and cows with clinical ketosis (n = 29)
      and fatty liver (n = 25) within the first 4 wk of lactation. In the present
      study, all blood samples were collected from the coccygeal vein in the early
      morning before feeding. RESULTS: Serum ANGPTL4 and FGF21 concentrations peaked at
      parturition, and declined rapidly over the following 2 wk Serum ANGPTL4 and FGF21
      concentrations were positively correlated with serum non-esterified fatty acids
      (NEFA) concentration (r = 0.856, P = 003; r = 0.848, P = 0.004, respectively).
      Cows with clinical ketosis and fatty liver had significantly higher serum ANGPTL4
      and FGF21 concentrations than healthy cows (P < 0.01). CONCLUSION: Serum ANGPTL4
      and FGF21 concentrations were elevated during peripartum period, suggesting that
      energy balance changes that were associated with parturition contributed
      significantly to these effects. Although FGF21 and ANGPTL4 could play important
      roles in the adaptation of energy metabolism, they may be involved in the
      pathological processes of energy metabolism disorders of dairy cows in the
      peripartum period.

PMID- 30103744
TI  - Correction to: The burden of war-injury in the Palestinian health care sector in
      Gaza Strip.
AB  - In the original publication of this article [1] the background section contained
      an inaccurate mention of the amount of civilian deaths in the 2014 Gaza war. In
      this correction article the incorrect and correct information are published for
      clarification.

PMID- 30103742
TI  - Altered miRNA profile in testis of post-cryptorchidopexy patients with non
      obstructive azoospermia.
AB  - BACKGROUND: Cryptorchidism is one of the most common causes of non-obstructive
      azoospermia (NOA) leading to male infertility. Despite various medical approaches
      been utilised, many patients still suffer from infertility. MicroRNAs (miRNAs)
      play vital roles in the progress of spermatogenesis; however, little is known
      about the miRNA expression profile in the testes. Therefore, the miRNA profile
      was assessed in the testis of post-cryptorchidopexy patients. METHODS: Three post
      cryptorchidopexy testicular tissue samples from patients aged 23, 26 and 28 years
      old and three testis tissues from patients with obstructive azoospermia
      (controls) aged 24, 25 and 36 years old were used in this study. Next-generation
      sequencing (NGS) was used to perform the miRNA expression profiling. Quantitative
      real-time reverse transcription polymerase chain reaction (qRT-PCR) assays were
      subsequently used to confirm the results of several randomly-selected and
      annotated miRNAs. RESULTS: A series of miRNAs were found to be altered between
      post-cryptorchidopexy testicular tissues and control tissues, including 297
      downregulated and 152 upregulated miRNAs. In the subsequent qRT-PCR assays, the
      expression levels of most of the selected miRNAs (9/12, P < 0.05) were consistent
      with the results of NGS technology. Furthermore, signal transduction, adaptive
      immune response and biological regulation were associated with the putative
      target genes of the differentially-expressed miRNAs via GO analysis. In addition,
      oxidative phosphorylation, Parkinson's disease and ribosomal pathways were shown
      to be enriched using KEGG pathway analysis of the differentially-expressed genes.
      CONCLUSIONS: This study provides a global view of the miRNAs involved in post
      cryptorchidopexy testicular tissues as well as the altered expression of miRNAs
      compared to control tissues, thus confirming the vital role of miRNAs in
      cryptorchidism.

PMID- 30103743
TI  - Evaluation of hepatic lipogenesis and antioxidant status of broiler chickens fed
      mountain celery.
AB  - BACKGROUND: Fatness is an unwanted side effect of genetic selection in broiler
      chickens. In this study, we introduce mountain celery powder as a feed supplement
      to suppress lipogenesis and improve antioxidant status in broiler chickens. Male
      broiler chicks (Ross 308) were fed a control diet or a diet that includes
      mountain celery (MC) at 7.5 gkg-1over 42 days. RESULTS: Body weight gain and feed
      conversion ratio significantly (P < 0.05) improved in chicks fed MC. A highly
      significant down-regulation of genes involved in hepatic lipogenesis including
      acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), malic enzyme (ME), and
      lipoprotein lipase (LPL) was observed in the liver of chickens fed MC. These
      birds, however, had greater compensatory upregulation in antioxidative genes SOD1
      and catalase in the liver compared to the birds that received the control diet.
      Birds received MC had significantly lower level of lipid peroxidation (1.59
      MUmol/L serum malondialdehyde) compared to birds from the control group (3.57
      MUmol/L; P = 0.0024). Birds fed MC had significantly (P < 0.05) lower circulatory
      concentrations of triacylglycerols, cholesterol, and LDL but higher
      concentrations of HDL. Relative liver weight and abdominal fat deposition were
      significantly reduced by feeding MC. CONCLUSIONS: It can be concluded that
      feeding birds MC significantly suppresses hepatic lipogenesis by down-regulating
      key hepatic lipogenic enzyme genes and boosts antioxidant capacity by up
      regulating hepatic antioxidantive genes.

PMID- 30103745
TI  - Safflower polysaccharide inhibits the development of tongue squamous cell
      carcinoma.
AB  - BACKGROUND: Safflower polysaccharide (SPS) is one of the most important active
      components of safflower (Carthamus tinctorius L.), which has been confirmed to
      have the immune-regulatory function and antitumor effect. This study aimed to
      explore the effects of safflower polysaccharide (SPS) on tongue squamous cell
      carcinoma (TSCC). METHODS: HN-6 cells were treated with 5 MUg/mL cisplatin and
      various concentrations of SPS (0, 0.02, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28
      mg/mL), and cell proliferation was measured. After treatment with 5 MUg/mL
      cisplatin and 0.64 mg/mL SPS, the induction of apoptosis and the protein and mRNA
      expression of Bax, Bcl-2, COX-2, and cleaved caspase-3 in HN-6 cells were
      quantified. In addition, HN-6 cells were implanted into mice to establish an in
      vivo tumor xenograft model. Animals were randomly assigned to three groups: SPS
      treatment, cisplatin treatment, and the model group (no treatment). The body
      weight, tumor volume, and tumor weight were measured, and the expression of the
      above molecules was determined. RESULTS: SPS treatment (0.02-0.64 mg/mL) for 24
      72 h inhibited HN-6 cell proliferation. In addition, 0.64 mg/mL SFP markedly
      induced apoptosis in HN-6 cells and arrested the cell cycle at the G0/G1 phase.
      Compared with the control group, the expression of Bcl-2 and COX-2 was markedly
      reduced by SPS treatment, whereas the expression of Bax and cleaved caspase-3 was
      increased. Moreover, SPS significantly inhibited the growth of the tumor
      xenograft, with similar changes in the expression of Bcl-2, COX-2, Bax, and
      cleaved caspase-3 in the tumor xenograft to the in vitro analysis. CONCLUSIONS:
      Our results indicated that SPS may inhibit TSCC development through regulation of
      Bcl-2, COX-2, Bax, and cleaved caspase-3 expression.

PMID- 30103746
TI  - Eigenspace generalized sidelobe canceller combined with SNR dependent coherence
      factor for plane wave imaging.
AB  - BACKGROUND: The eigenspace generalized sidelobe canceller (EGSC) beamformer
      combined with a signal-to-noise ratio (SNR) dependent coherence factor (CF) is
      suggested for coherent plane wave compounding (PW) imaging. Conventional CF based
      methods such as generalized CF and subarray CF can improve the image quality,
      however, they are not suitable for low SNR. On the other hand, the EGSC CF based
      approach can introduce improvements in image quality, however, in PW imaging is
      susceptible to suffer from degradation due to low SNR which leads to a poor image
      quality. To overcome this limitation, the SNR dependent CF method is suggested
      for application in such situations due to its ability to control the SNR levels.
      METHODS: The Field II and the Verasonics ultrasound imaging system with a L11-4v
      array transducer with a contrast resolution phantom were used to capture the
      plane wave sequences of simulation and experimental data, respectively. The
      performance evaluation using full width at half maximum (FWHM), contrast (CR and
      CNR) and the speckle statistics by using the signal to noise ratio (SNR)
      complemented by the Rayleigh distribution analysis was performed. In order to
      evaluate the performance of the [Formula: see text] (the SNR CF) beamformer, the
      comparison is done with particular importance to other CF-based approaches such
      as [Formula: see text] (the generalized CF) and, [Formula: see text] (the
      subarray CF) respectively. RESULTS: Taking DAS as reference, [Formula: see text]
      showed 30.3 and 39.5% of improvement for [Formula: see text] and [Formula: see
      text], respectively, when using experimental data. The proposed method also
      slightly outperforms the [Formula: see text] and [Formula: see text] methods for
      [Formula: see text], [Formula: see text], and speckle statistics assessment.
      CONCLUSION: The [Formula: see text] is, therefore, suitable for CPWC by improving
      the spatial resolution and contrast while preserving the speckle pattern.

PMID- 30103747
TI  - 'We are planning to leave, all of us'-a realist study of mechanisms explaining
      healthcare employee turnover in rural Ethiopia.
AB  - BACKGROUND: We study healthcare employees' turnover intentions in the Afar
      National Regional State of Ethiopia. This rural region is experiencing the
      globally felt crisis in human resources, which is inhibiting its ability to meet
      health-related sustainable development goals. METHODS: Realist case study which
      combines literature study and qualitative analysis of interview and focus group
      discussion data, following a realist case study protocol. RESULTS: A large
      majority of employees has turnover intentions. Building on Herzberg's two-factor
      theory, person-environment fit theory, as well as recent sub-Saharan evidence,
      analysis of the collected data yields four turnover mechanisms: (1) lack of
      social and personal opportunities in the region, (2) dissonance between
      management logic and professional logic, (3) standards of service operations are
      hard to accept, and (4) lack of financial improvement opportunities. CONCLUSIONS:
      While the first and fourth mechanisms may be out of reach for local (human
      resource) management interventions, the second and third mechanisms proposed to
      explain health workforce turnover appear to be amenable to local (human resource)
      management interventions to strengthen healthcare. These mechanisms are likely to
      play a role in other remote sub-Saharan regions as well.

PMID- 30103748
TI  - Improving accuracy of corneal power measurement with partial coherence
      interferometry after corneal refractive surgery using a multivariate polynomial
      approach.
AB  - BACKGROUND: To improve accuracy of IOLMaster (Carl Zeiss, Jena, Germany) in
      corneal power measurement after myopic excimer corneal refractive surgery (MECRS)
      using multivariate polynomial analysis (MPA). METHODS: One eye of each of 403
      patients (mean age 31.53 +/- 8.47 years) was subjected to MECRS for a myopic
      defect, measured as spherical equivalent, ranging from - 9.50 to - 1 D (mean -
      4.55 +/- 2.20 D). Each patient underwent a complete eye examination and IOLMaster
      scan before surgery and at 1, 3 and 6 months follow up. Axial length (AL),
      flatter keratometry value (K1), steeper keratometry value (K2), mean keratometry
      value (KM) and anterior chamber depth measured from the corneal endothelium to
      the anterior surface of the lens (ACD) were used in a MPA to devise a method to
      improve accuracy of KM measurements. RESULTS: Using AL, K1, K2 and ACD measured
      after surgery in polynomial degree 2 analysis, mean error of corneal power
      evaluation after MECRS was + 0.16 +/- 0.19 D. CONCLUSIONS: MPA was found to be an
      effective tool in devising a method to improve precision in corneal power
      evaluation in eyes previously subjected to MECRS, according to our results.

PMID- 30103749
TI  - Facilitators and strategies to implement clinical pharmacy services in a
      metropolis in Northeast Brazil: a qualitative approach.
AB  - BACKGROUND: Clinical Pharmacy Services (CPS) are a reality in many health systems
      around the world. However, there are few studies that discuss the facilitators
      and the strategies to implement CPS in healthcare systems. In this way, the
      objective of this study was to identify the facilitators and strategies involved
      in the CPS implementation process in some public health units in a metropolis in
      the Northeast Brazil. METHODS: A qualitative study was carried out with health
      system pharmacists and managers who experienced the implementation of CPS.
      Therefore, focus groups were conducted with pharmacists, and the interviews with
      the managers. The discussions were carried out through semi-structured scripts
      and were recorded in audio and videos, after the signature of the consent form.
      The recordings were transcribed and analyzed independently through content
      analysis, followed by consensus meetings between researchers. RESULTS: Two focus
      groups were conducted, with an average of seven pharmacists per group, and five
      interviews with local health managers. Participants reported 39 facilitators who
      were related to the categories: local healthcare network, healthcare team,
      pharmacists and implementation process of the CPS. And 21 strategies attributed
      to the following categories: local healthcare network, pharmacists and
      implementation process of the CPS. CONCLUSIONS: This study identified
      facilitators and strategies of the implementation of CPS. Most of the positive
      experiences were related to the clinical skills and proactive attitudes of
      pharmacists. These findings may support pharmacists and health managers to
      implement CPS in health systems.

PMID- 30103750
TI  - Characterization, yield optimization, scale up and biopreservative potential of
      fermencin SA715, a novel bacteriocin from Lactobacillus fermentum GA715 of goat
      milk origin.
AB  - BACKGROUND: Emergence of antibiotic resistance and growing consumer trend towards
      foods containing biopreservatives stimulated the search for alternative
      antimicrobials. This research is aimed at characterizing, investigating the
      mechanism of action, scale up optimization and evaluating the biopreservative
      potential of a bacteriocin from Lactobacillus fermentum. RESULTS: Fermencin SA715
      is a novel, broad-spectrum, non-pore-forming and cell wall-associated bacteriocin
      isolated from L. fermentum GA715 of goat milk origin. A combination of
      hydrophobic interaction chromatography, solid-phase extraction and reversed-phase
      HPLC was necessary for purification of the bacteriocin to homogeneity. It has a
      molecular weight of 1792.537 Da as revealed by MALDI-TOF mass spectrometry.
      Fermencin SA715 is potent at micromolar concentration, possesses high thermal and
      pH stability and inactivated by proteolytic enzymes thereby revealing its
      proteinaceous nature. Biomass accumulation and production of fermencin SA715 was
      optimum in a newly synthesized growth medium. Fermencin SA715 did not occur in
      the absence of manganese(II) sulphate. Tween 80, ascorbic acid, sodium citrate
      and magnesium sulphate enhanced the production of fermencin SA715. Sucrose is the
      preferred carbon source for growth and bacteriocin production. Sodium chloride
      concentration higher than 1% suppressed growth and production of fermencin SA715.
      Optimum bacteriocin production occurred at 37  degrees C and pH 6-7. Scale up of
      fermencin SA715 production involved batch fermentation in a bioreactor at a
      constant pH of 6.5 which resulted in enhanced production. Fermencin SA715 doubled
      the shelf life and improved the microbiological safety of fresh banana.
      Bacteriocin application followed by refrigeration tripled the shell life of
      banana. CONCLUSIONS: This study reveals the huge potential of fermencin SA715 as
      a future biopreservative for bananas and reveals other interesting
      characteristics which can be exploited in the preservation of other foods.
      Furthermore insights on the factors influencing the production of fermencin SA715
      have been revealed and optimized condition for its production has been
      established facilitating future commercial production.

PMID- 30103752
TI  - Case report: synovial sarcoma of the axilla with brachial plexus involvement.
AB  - BACKGROUND: Synovial sarcoma is a rare soft tissue sarcoma which most commonly
      affects the extremities of young adults. Axilla involvement by this sarcoma is
      very rare especially with involvement of the brachial plexus. This combination
      adds to the challenge in approaching such tumors which might significantly affect
      survival and function. CASE PRESENTATION: Herein, we present a 48-year-old female
      patient who presented with an isolated painless lump in her right axilla.
      Initially, her workup, looking for possible breast cancer, included fine-needle
      aspiration (FNA) which did not provide the diagnosis. Core-needle biopsy,
      performed later, revealed monophasic synovial sarcoma. Her workup studies
      revealed no metastasis. Then, through extensile deltopectoral approach, the tumor
      was dissected out from within the brachial plexus. Ulnar nerve was sacrificed in
      order not to compromise the surgical margins which were confirmed tumor free by
      final pathology. The patient did not receive chemotherapy or radiation upon
      consultations with medical and radiation oncology teams. Her follow-up revealed
      no tumor recurrence with no restriction of her right shoulder motion. CONCLUSION:
      Our case report represents a very rare occurrence of synovial sarcoma in the
      axilla with involvement of the brachial plexus. When clinical and radiological
      findings are suggestive of soft tissue sarcoma of the axilla, we recommend
      getting core-needle biopsy rather than fine-needle aspiration for earlier
      diagnosis. Early referral and multidisciplinary approach may contribute to better
      management.

PMID- 30103751
TI  - Metabolism of primaquine in normal human volunteers: investigation of phase I and
      phase II metabolites from plasma and urine using ultra-high performance liquid
      chromatography-quadrupole time-of-flight mass spectrometry.
AB  - BACKGROUND: Primaquine (PQ), an 8-aminoquinoline, is the only drug approved by
      the United States Food and Drug Administration for radical cure and prevention of
      relapse in Plasmodium vivax infections. Knowledge of the metabolism of PQ is
      critical for understanding the therapeutic efficacy and hemolytic toxicity of
      this drug. Recent in vitro studies with primary human hepatocytes have been
      useful for developing the ultra high-performance liquid chromatography coupled
      with high-resolution mass spectrometric (UHPLC-QToF-MS) methods for simultaneous
      determination of PQ and its metabolites generated through phase I and phase II
      pathways for drug metabolism. METHODS: These methods were further optimized and
      applied for phenotyping PQ metabolites from plasma and urine from healthy human
      volunteers treated with single 45 mg dose of PQ. Identity of the metabolites was
      predicted by MetaboLynx using LC-MS/MS fragmentation patterns. Selected
      metabolites were confirmed with appropriate standards. RESULTS: Besides PQ and
      carboxy PQ (cPQ), the major plasma metabolite, thirty-four additional metabolites
      were identified in human plasma and urine. Based on these metabolites, PQ is
      viewed as metabolized in humans via three pathways. Pathway 1 involves direct
      glucuronide/glucose/carbamate/acetate conjugation of PQ. Pathway 2 involves
      hydroxylation (likely cytochrome P450-mediated) at different positions on the
      quinoline ring, with mono-, di-, or even tri-hydroxylations possible, and
      subsequent glucuronide conjugation of the hydroxylated metabolites. Pathway 3
      involves the monoamine oxidase catalyzed oxidative deamination of PQ resulting in
      formation of PQ-aldehyde, PQ alcohol and cPQ, which are further metabolized
      through additional phase I hydroxylations and/or phase II glucuronide
      conjugations. CONCLUSION: This approach and these findings augment our
      understanding and provide comprehensive view of pathways for PQ metabolism in
      humans. These will advance the clinical studies of PQ metabolism in different
      populations for different therapeutic regimens and an understanding of the role
      these play in PQ efficacy and safety outcomes, and their possible relation to
      metabolizing enzyme polymorphisms.

PMID- 30103753
TI  - Community involvement in design, implementation and evaluation of nutrition
      interventions to reduce chronic diseases in indigenous populations in the U.S.: a
      systematic review.
AB  - BACKGROUND: Indigenous peoples of the United States disproportionately experience
      chronic diseases associated with poor nutrition, including obesity and diabetes.
      While chronic disease related health disparities among Indigenous people are well
      documented, it is unknown whether interventions adequately address these health
      disparities. In addition, it is unknown whether and to what extent interventions
      are culturally adapted or tailored to the unique culture, worldview and nutrition
      environments of Indigenous people. The aim of this review was to identify and
      characterize nutrition interventions conducted with Indigenous populations in the
      US, and to determine whether and to what degree communities are involved in
      intervention design, implementation and evaluation. METHODS: Peer-reviewed
      articles were identified using MEDLINE. Articles included were published in
      English in a refereed journal between 2000 and 2015, reported on a diet-related
      intervention in Indigenous populations in the US, and reported outcome data. Data
      extracted were program objectives and activities, target population, geographic
      region, formative research to inform design and evaluation, partnership, capacity
      building, involvement of the local food system, and outcomes. Narrative synthesis
      of intervention characteristics and the degree and type of community involvement
      was performed. RESULTS: Of 1060 records identified, 49 studies were included.
      Overall, interventions were successful in producing changes in knowledge,
      behavior or health (79%). Interventions mostly targeted adults in the Western
      region and used a pre-test, post-test design. Involvement of communities in
      intervention design, implementation, and evaluation varied from not at all to
      involvement at all stages. Of programs reporting significant changes in outcomes,
      more than half used at least three strategies to engage communities. However,
      formative research to inform the evaluation was not performed to a great degree,
      and fewer than half of the programs identified described involvement of the local
      food system. CONCLUSIONS: The extent of use of strategies to promote community
      engagement in programs reporting significant outcomes is notable. In planning
      interventions in Indigenous groups, researchers should consider ways to involve
      the community in intervention design, execution and evaluation. There is a
      particular need for studies focused on Indigenous youth in diverse regions of the
      US to further address diet-related chronic conditions.

PMID- 30103754
TI  - Funding models and medical dominance in interdisciplinary primary care teams:
      qualitative evidence from three Canadian provinces.
AB  - BACKGROUND: Primary care in Canada is the first point of entry for patients
      needing specialized services, the fundamental source of care for those living
      with chronic illness, and the main supplier of preventive services. Increased
      pressures on the system lead to changes such as an increased reliance on
      interdisciplinary teams, which are advocated to have numerous advantages. The
      functioning of teams largely depends on inter-professional relationships that can
      be supported or strained by the financial arrangements within teams. We assess
      which types of financial environments perpetuate and which reduce the challenge
      of medical dominance. METHODS: Using qualitative interview data from 19
      interdisciplinary teams/networks in three Canadian provinces, as well as related
      policy documents, we develop a typology of financial environments along two
      dimensions, financial hierarchy and multiplicity of funding sources. A financial
      hierarchy is created when the incomes of some providers are a function of the
      incomes of other providers. A multiplicity of funding sources is created when
      team funding is provided by several funders and a team faces multiple lines of
      accountability. RESULTS: We argue that medical dominance is perpetuated with
      higher degrees of financial hierarchy and higher degrees of multiplicity. We show
      that the financial environments created in the three provinces have not supported
      a reduction in medical dominance. The longstanding Community Health Centre model,
      however, displays the least financial hierarchy and the least multiplicity-an
      environment least fertile for medical dominance. CONCLUSIONS: The functioning of
      interdisciplinary primary care teams can be negatively affected by the unique
      positioning of the medical profession. The financial environment created for
      teams is an important consideration in policy development, as it plays an
      important role in establishing inter-professional relationships. Policies that
      reduce financial hierarchies and funding multiplicities are optimal in this
      regard.

PMID- 30103755
TI  - Epidemiological characterization of malaria in rural southern Tanzania following
      China-Tanzania pilot joint malaria control baseline survey.
AB  - BACKGROUND: Malaria is an important public health problem in Tanzania. The latest
      national malaria data suggests rebound of the disease in the country. Anopheles
      arabiensis, a mosquito species renowned for its resilience against existing
      malaria vector control measures has now outnumbered the endophagic and
      anthrophilic Anopheles gambiae sensu stricto as the dominant vector. Vector
      control measures, prophylaxis and case management with artemisinin-based
      combination therapy (ACT) are the main control interventions. This paper presents
      and discusses the main findings from a baseline household survey that was
      conducted to determine malaria parasite prevalence and associated risk exposures
      prior to piloting the T3-initiative of World Health Organization integrated with
      Chinese malaria control experience aimed at additional reduction of malaria in
      the area. METHODS: The study was conducted from 4 sub-district divisions in
      Rufiji District, southern Tanzania: Ikwiriri, Kibiti, Bungu, and Chumbi. Malaria
      transmission is endemic in the area. It involved 2000 households that were
      randomly selected from a list of all households that had been registered from the
      area. Residents in sampled households were interviewed on a range of questions
      that included use of long-lasting insecticidal nets (LLINs) the night prior to
      the interview and indicators of socio-economic status. Blood drops were also
      collected on blood slides that were examined for malaria parasites using
      microscopes. RESULTS: The study observed an average malaria parasite prevalence
      of 13% across the selected site. Its distribution was 5.6, 12.8, 16.7, and 18%
      from Ikwiriri, Kibiti, Bungu, and Chumbi wards, respectively. The corresponding
      LLIN use discovered were 57.5% over the district. The highest usage was observed
      from Ikwiriri at 69.6% and the lowest from Bungu at 46.3%. A statistically
      significant variation in parasitaemia between socio-economic quintiles was
      observed from the study. Males were more parasitaemic than females (p value =
      0.000). DISCUSSION AND CONCLUSION: The findings have been discussed in the light
      of results from Tanzania Demographic and Health Survey-Malaria Indicator Survey,
      2015-2016 and other related studies, together with goals and targets set for
      malaria control. The paper also discusses the observed parasitaemia in relation
      to reported LLIN use and its distribution by some important factors as they were
      explored from the study. It has been concluded that malaria burden is now
      concentrated on the fringes of the settlements where the poorest section of the
      population is concentrated and LLIN usage is lower than the national average and
      targets set by national and global malaria control initiatives.

PMID- 30103756
TI  - Genome-scale CRISPR-Cas9 knockout screening in gastrointestinal stromal tumor
      with Imatinib resistance.
AB  - Genome-scale CRISPR-Cas9 Knockout Screening was applied to investigate novel
      targets in imatinib-resistant gastrointestinal stromal tumor (GIST). 20 genes and
      2 miRNAs have been selected by total reads of sgRNA and sgRNA diversity, which
      has been further validated in imatinib-resistant GIST cells by CCK8 and qPCR
      analysis. Our study has finally revealed 9 genes (DBP, NR3C1, TCF12, TP53, ZNF12,
      SOCS6, ZFP36, ACYP1, and DRD1) involved in imatinib-resistant GIST-T1 cells. TP53
      and SOCS6 may be the most promising candidate genes for imatinib-resistance due
      to the possible signaling pathway, such as apoptosis pathway and Wnt signaling
      pathway, JAK-STAT signaling pathway. It is necessary to perform more studies to
      discover novel targets in imatinib-resistant GIST, including DBP, NR3C1, TCF12,
      ZNF12, ZFP36, ACYP1 and DRD1.

PMID- 30103757
TI  - Advancing the science behind human resources for health: highlights from the
      Health Policy and Systems Research Reader on Human Resources for Health.
AB  - Health workers are central to people-centred health systems, resilient economies
      and sustainable development. Given the rising importance of the health workforce,
      changing human resource for health (HRH) policy and practice and recent health
      policy and systems research (HPSR) advances, it is critical to reassess and
      reinvigorate the science behind HRH as part of health systems strengthening and
      social development more broadly. Building on the recently published Health Policy
      and Systems Research Reader on Human Resources for Health (the Reader), this
      commentary reflects on the added value of HPSR underpinning HRH. HPSR does so by
      strengthening the multi-disciplinary base and rigour of HRH research by (1)
      valuing diverse research inferences and (2) deepening research enquiry and
      quality. It also anchors the relevance of HRH research for HRH policy and
      practice by (3) broadening conceptual boundaries and (4) strengthening policy
      engagement. Most importantly, HPSR enables us to transform HRH from being
      faceless numbers or units of health producers to the heart and soul of health
      systems and vital change agents in our communities and societies. Health workers'
      identities and motivation, daily routines and negotiations, and training and
      working environments are at the centre of successes and failures of health
      interventions, health system functioning and broader social development. Further,
      in an increasingly complex globalised economy, the expansion of the health sector
      as an arena for employment and the liberalisation of labour markets has
      contributed to the unprecedented movement of health workers, many or most of whom
      are women, not only between public and private health sectors, but also across
      borders. Yet, these political, human development and labour market realities are
      often set aside or elided altogether. Health workers' lives and livelihoods,
      their contributions and commitments, and their individual and collective agency
      are ignored. The science of HRH, offering new discoveries and deeper
      understanding of how universal health coverage and the Sustainable Development
      Goals are dependent on millions of health workers globally, has the potential to
      overcome this outdated and ineffective orthodoxy.

PMID- 30103758
TI  - Reconstruction options following pancreaticoduodenectomy after Roux-en-Y gastric
      bypass: a systematic review.
AB  - BACKGROUND: Obesity is a risk factor for pancreatic cancer which may be treated
      with Roux-en-Y gastric bypass and represents an increasing morbidity. Post-RYGB
      anatomy poses considerable challenges for reconstruction after
      pancreaticoduodenectomy (PD), a growing problem encountered by surgeons. We
      characterize specific strategies used for post-PD reconstruction in the RYGB
      patient. METHODS: PubMed search was performed using MeSH terms "Gastric Bypass"
      and "Pancreaticoduodenectomy" between 2000 and 2018. Articles reporting cases of
      pancreaticoduodenectomy in post-RYGB patients were included and systematically
      reviewed for this study. RESULTS: Three case reports and five case series (25
      patients) addressed PD after RYGB; we report one additional case. The typical
      post-gastric bypass PD patient is a woman in the sixth decade of life, presenting
      most commonly with pain (69.2%) and/or jaundice (53.8%), median 5 years after
      RYGB. Five post-PD reconstructive options are reported. Among these, the gastric
      remnant was resected in 18 cases (69.2%), with reconstruction of biliopancreatic
      drainage most commonly achieved using the distal jejunal segment of the pre
      existing biliopancreatic limb (73.1%). Similarly, in the eight cases where the
      gastric remnant was spared (30.8%), drainage was most commonly performed using
      the distal jejunal segment of the biliopancreatic limb (50%). Among the 17 cases
      reporting follow-up data, median was 27 months. CONCLUSION: Reconstruction
      options after PD in the post-RYGB patient focus on resection or preservation
      gastric remnant, as well as creation of new biliopancreatic limb. Insufficient
      data exists to make recommendations regarding the optimal reconstruction option,
      yet surgeons must prepare for the possible clinical challenge. PD reconstruction
      post-RYGB requires evaluation through prospective studies.

PMID- 30103759
TI  - Determinants of quality of life among Malaysian cancer patients: a cross
      sectional study.
AB  - BACKGROUND: Cancer is a serious public health problem not only in Malaysia, also
      worldwide. The aim of this study was to determine the determinants of quality of
      life (QOL) among cancer patients in Peninsular Malaysia. METHODS: A cross
      sectional study was conducted among 2120 cancer patients in Peninsular Malaysia,
      between April 2016 to January 2017. All cancer patients aged 18 years old and
      above, Malaysian citizens and undergoing cancer treatment at government hospitals
      were approached to participate in this study and requested to complete a set of
      validated questionnaires. Inferential statistical tests such as t-test and one
      way ANOVA were used to determine the differences between demographic variables,
      physical effects, clinical factors, psychological effects and self-esteem with
      the quality of life of cancer patients. Predictor(s) of quality of life were
      determined by using Multivariate linear regression models. RESULT: A total 1620
      out of 2120 cancer patients participated in this study, giving a response rate of
      92%. The majority of cancer patients were female 922 (56.9%), Malays 1031
      (63.6%), Muslim 1031 (63.6%), received chemotherapy treatment 1483 (91.5%).
      Overall, 1138 (70.2%) of the patients had depression and 1500 (92.6%) had
      anxiety. Statistically significant associations were found between QOL and
      clinical factors, physical side effects of cancer, psychological effects and self
      esteem (p < 0.05). However, among socio-demographics only age, race, religion,
      working status were significantly associated with QOL. Based on the multivariate
      regression analysis, the main predictors of QOL among cancer patients in Malaysia
      were age, self-esteem as positive predictors, and Indian race, nausea, fatigue,
      hair loss, bleeding as negative predictors. CONCLUSION: The findings of this
      study provide a scientific basis to develop a comprehensive program for improving
      quality of life of cancer patients in Malaysia.

PMID- 30103760
TI  - Punching above their weight: a network to understand broader determinants of
      increasing life expectancy.
AB  - BACKGROUND: Life expectancy initially improves rapidly with economic development
      but then tails off. Yet, at any level of economic development, some countries do
      better, and some worse, than expected - they either punch above or below their
      weight. Why this is the case has been previously researched but no full
      explanation of the complexity of this phenomenon is available. NEW RESEARCH
      NETWORK: In order to advance understanding, the newly formed Punching Above Their
      Weight Research Network has developed a model to frame future research. It
      provides for consideration of the following influences within a country:
      political and institutional context and history; economic and social policies;
      scope for democratic participation; extent of health promoting policies affecting
      socio-economic inequities; gender roles and power dynamics; the extent of civil
      society activity and disease burdens. CONCLUSION: Further research using this
      framework has considerable potential to advance effective policies to advance
      health and equity.

PMID- 30103761
TI  - Simulation-based low-dose, high-frequency plus mobile mentoring versus
      traditional group-based training approaches on day of birth care among maternal
      and newborn healthcare providers in Ebonyi and Kogi States, Nigeria; a randomized
      controlled trial.
AB  - BACKGROUND: There is limited information from low and middle-income countries on
      learning outcomes, provider satisfaction and cost-effectiveness on the day of
      birth care among maternal and newborn health workers trained using onsite
      simulation-based low-dose high frequency (LDHF) plus mentoring approach compared
      to the commonly employed offsite traditional group-based training (TRAD). The
      LDHF approach uses in-service learning updates to deliver information based on
      local needs during short, structured, onsite, interactive learning activities
      that involve the entire team and are spaced over time to optimize learning. The
      aim of this study will be to compare the effectiveness and cost of LDHF versus
      TRAD approaches in improving knowledge and skill in maternal and newborn care and
      to determine trainees' satisfaction with the approaches in Ebonyi and Kogi
      states, Nigeria. METHODS: This will be a prospective cluster randomized control
      trial. Sixty health facilities will be randomly assigned for day of birth care
      health providers training through either LDHF plus mobile mentoring (intervention
      arm) or TRAD (control arm). There will be 150 trainees in each arm. Multiple
      choices questionnaires (MCQs), objective structured clinical examinations
      (OSCEs), cost and satisfaction surveys will be administered before and after the
      trainings. Quantitative data collection will be done at months 0 (baseline), 3
      and 12. Qualitative data will also be collected at 12-month from the LDHF arm
      only. Descriptive and inferential statistics will be used as appropriate.
      Composite scores will be computed for selected variables to determine areas where
      service providers have good skills as against areas where their skills are poor
      and to compare skills and knowledge outcomes between the two groups at 0.05 level
      of statistical significance. DISCUSSION: There is some evidence that LDHF,
      simulation and practice-based training approach plus mobile mentoring results in
      improved skills and health outcomes and is cost-effective. By comparing
      intervention and control arms the authors hope to replicate similar results,
      evaluate the approach in Nigeria and provide evidence to Ministry of Health on
      how and which training approach, frequency and setting will result in the
      greatest return on investment. TRIAL REGISTRATION: The trial was retrospectively
      registered on 24th August, 2017 at ClinicalTrials.Gov: NCT03269240 .

PMID- 30103762
TI  - Clonal raider ant brain transcriptomics identifies candidate molecular mechanisms
      for reproductive division of labor.
AB  - BACKGROUND: Division of labor between reproductive queens and workers that
      perform brood care is a hallmark of insect societies. However, studies of the
      molecular basis of this fundamental dichotomy are limited by the fact that the
      caste of an individual cannot typically be experimentally manipulated at the
      adult stage. Here we take advantage of the unique biology of the clonal raider
      ant, Ooceraea biroi, to study brain gene expression dynamics during
      experimentally induced transitions between reproductive and brood care behavior.
      RESULTS: Introducing larvae that inhibit reproduction and induce brood care
      behavior causes much faster changes in adult gene expression than removing
      larvae. In addition, the general patterns of gene expression differ depending on
      whether ants transition from reproduction to brood care or vice versa, indicating
      that gene expression changes between phases are cyclic rather than pendular.
      Finally, we identify genes that could play upstream roles in regulating
      reproduction and behavior because they show large and early expression changes in
      one or both transitions. CONCLUSIONS: Our analyses reveal that the nature and
      timing of gene expression changes differ substantially depending on the direction
      of the transition, and identify a suite of promising candidate molecular
      regulators of reproductive division of labor that can now be characterized
      further in both social and solitary animal models. This study contributes to
      understanding the molecular regulation of reproduction and behavior, as well as
      the organization and evolution of insect societies.

PMID- 30103763
TI  - Barriers to accessing adequate maternal care in Georgia: a qualitative study.
AB  - BACKGROUND: The maternal health outcomes in Georgia are linked to shortcomings in
      healthcare such as inequities in access to adequate maternal care. Due to the
      macro-level, quantitative approach applied in most previous studies, little is
      known about the underlying reasons that influence maternal care and care-seeking
      behaviour of pregnant women. METHODS: This qualitative study explores the
      stakeholders' perspectives on access to adequate maternal care in Georgia. Focus
      group discussions are conducted with mothers who gave birth within in the past
      four years and in-depth interviews are conducted with decision-makers and health
      professionals in the field. Five access-related aspects are studied:
      availability, appropriateness, affordability, approachability and acceptability
      of maternal care. The method of direct content analysis is applied. RESULTS:
      Results indicate problems with maternal care standards, inequalities across
      population groups and drawbacks in maternal care financing. This includes gaps in
      clinical quality and staff skills, as well as poor communication between women
      and health professionals. Geographical barriers to adequate maternal care exist
      in rural and mountainous areas due to the weak infrastructure (poor roads and
      weak transportation), in addition to financial hardships. Despite improvements in
      the coverage of maternal care, affordability remains an access barrier. Poorer
      population groups are financially unprotected from the high out-of-pocket
      payments for maternal care services. CONCLUSION: These findings imply that micro
      level indicators, such as disrespectful behaviour of health professionals and
      affordability of care, should be taken into account when assessing maternal care
      provision in Georgia. It should complement the existing macro-level indicators
      for a comprehensive evaluation of maternal care.

PMID- 30103764
TI  - Measuring implementation fidelity of school-based obesity prevention programmes:
      a systematic review.
AB  - BACKGROUND: Until now, there is no clear overview of how fidelity is assessed in
      school-based obesity prevention programmes. In order to move the field of obesity
      prevention programmes forward, the current review aimed to 1) identify which
      fidelity components have been measured in school-based obesity prevention
      programmes; 2) identify how fidelity components have been measured; and 3) score
      the quality of these methods. METHODS: Studies published between January 2001
      October 2017 were selected from searches in PubMed, EMBASE, PsycINFO, CINAHL,
      Cochrane Library and ERIC. We included studies examining the fidelity of obesity
      prevention programmes (nutrition and/or physical activity and/or sitting) at
      school (children aged 4-18 year) measuring at least one component of
      implementation fidelity. A data extraction was performed to identify which and
      how fidelity components were measured. Thereafter, a quality assessment was
      performed to score the quality of these methods. We scored each fidelity
      component on 7 quality criteria. Each fidelity component was rated high (> 75%
      positive), moderate (50-75%) or low (< 50%). RESULTS: Of the 26,294 retrieved
      articles, 73 articles reporting on 63 different studies were included in this
      review. In 17 studies a process evaluation was based on a theoretical framework.
      In total, 120 fidelity components were measured across studies: dose was measured
      most often (N = 50), followed by responsiveness (N = 36), adherence (N = 26) and
      quality of delivery (N = 8). There was substantial variability in how fidelity
      components were defined as well as how they were measured. Most common methods
      were observations, logbooks and questionnaires targeting teachers. The quality
      assessment scores ranged from 0 to 86%; most fidelity components scored low
      quality (n = 77). CONCLUSIONS: There is no consensus on the operationalisation of
      concepts and methods used for assessing fidelity in school-based obesity
      prevention programmes and the quality of methods used is weak. As a result, we
      call for more consensus on the concepts and clear reporting on the methods
      employed for measurements of fidelity to increase the quality of fidelity
      measurements. Moreover, researchers should focus on the relation between fidelity
      and programme outcomes and determine to what extent adaptations to programmes
      have been made, whilst still being effective.

PMID- 30103765
TI  - Induction chemotherapy plus concurrent chemoradiotherapy versus induction
      chemotherapy plus volumetric modulated arc therapy alone in the treatment of
      stage II-IVB nasopharyngeal carcinoma patients: a retrospective controlled study.
AB  - BACKGROUND: In the era of intensity-modulated radiotherapy (IMRT), the role of
      additional concurrent chemotherapy (CC) to radiotherapy (RT) after induction
      chemotherapy (IC) compared to IC followed by RT alone remains unclear for stage
      II-IVB nasopharyngeal carcinoma (NPC) patients. The aim of this study was to
      evaluate the efficacy and toxicities of IC/RT and IC/CCRT in the treatment of NPC
      with volumetric modulated arc therapy (VMAT). METHODS: From January 2012 to March
      2016, a total of 217 NPC patients were retrospectively assessed. Of the 217
      patients, 139 patients received IC followed by VMAT alone and 78 patients
      received IC plus CCRT. Overall survival (OS), progression-free survival (PFS) and
      toxicities were assessed. RESULTS: The 5-year OS, PFS rates were 57.5%, 41.8% and
      47.8%, 38.4% for the IC/RT and IC/CCRT arms, respectively, without significant
      difference in survival between the two groups (both p > 0.05). Multivariate
      analysis indicated that treatment modality (IC/RT vs. IC/CCRT) was not an
      independent prognostic factor for OS or PFS. Grade 3-4 leukopenia/neutropenia
      (3.60% vs. 20.51%, p < 0.001), gastrointestinal disorder
      (nausea/vomiting/diarrhea, 2.16% vs. 41.03%, p < 0.001), mucositis (29.50% vs.
      47.44%, p = 0.01) and xerostomia (34.53% vs. 48.72%, p = 0.04) were more frequent
      in the IC/ CCRT arm than in the IC/RT arm during VMAT. CONCLUSIONS: No
      significant difference in OS and PFS was observed between IC plus VMAT alone and
      IC/CCRT in the treatment of stage II-IVB NPC patients, however, more side effects
      were observed in the IC/CCRT arm.

PMID- 30103767
TI  - Survey for major viruses in commercial Vitis vinifera wine grapes in Ontario.
AB  - BACKGROUND: In recent years, the Ontario grape and wine industry has experienced
      outbreaks of viral diseases across the province. Little is known about the
      prevalence of viruses and viral diseases in Ontario. Since 2015, we have
      conducted large-scale surveys for major viruses in commercial wine grapes in
      order to obtain a comprehensive understanding of the prevalence and severity of
      viral diseases in Ontario. METHODS: A total of 657 composite leaf samples
      representing 3285 vines collected from 137 vine blocks of 33 vineyards from three
      appellations: Niagara Peninsula, Lake Erie North Shore and Prince Edward County.
      These samples covered six major red cultivars and five major white grape
      cultivars. Using a multiplex RT-PCR format, we tested these samples for 17
      viruses including those involved in all major viral diseases of the grapevine,
      such as five grapevine leafroll-associated viruses (GLRaV-1, 2, 3, 4, 7),
      grapevine red blotch virus (GRBV), grapevine Pinot gris virus (GPGV), grapevine
      rupestris stem sitting-associated virus (GRSPaV), grapevine virus A (GVA),
      grapevine virus B (GVB), grapevine fleck virus (GFkV), arabis mosaic virus
      (ArMV), tomato ringspot virus (ToRSV), trapevine fanleaf virus (GFLV), among
      others. RESULTS: Fourteen of the 17 viruses were detected from these samples and
      the predominant viruses are GRSPaV, GLRaV-3, GFkV, GPGV and GRBaV with an
      incidence of 84.0, 47.9, 21.8, 21.6 and 18.3%, respectively. As expected, mixed
      infections with multiple viruses are common. 95.6% of the samples included in the
      survey were infected with at least one virus; 67% of the samples with 2-4 viruses
      and 4.7% of the samples with 5-6 viruses. The major grape cultivars all tested
      positive for these major viruses. The results also suggested that the use of
      infected planting material may have been one of the chief factors responsible for
      the recent outbreaks of viral diseases across the province. CONCLUSIONS: This is
      the first such comprehensive survey for grapevine viruses in Ontario and one of
      the most extensive surveys ever conducted in Canada. The recent outbreaks of
      viral diseases in Ontario vineyards were likely caused by GLRaV-3, GRBV and GPGV.
      Findings from this survey provides a baseline for the grape and wine industry in
      developing strategies for managing grapevine viral diseases in Ontario vineyards.

PMID- 30103766
TI  - Healthcare provider-patient communication: a qualitative study of women's
      perceptions during childbirth.
AB  - BACKGROUND: There is limited information on the impact of effective healthcare
      provider-patient communication on facility-based delivery in Malawi. The purpose
      of this study was to examine the nature of communication in the maternity ward,
      identify facilitators and barriers to healthcare provider-patient communication,
      and understand how they affect maternal healthcare. METHODS: This was a
      descriptive study that used qualitative data collection and analysis methods.
      Data were collected through face-to-face in-depth interviews using a semi
      structured interview guide to collect information about women's perceptions of
      their communication with healthcare providers. A total of 30 in-depth interviews
      were conducted with women admitted for delivery in six health facilities drawn
      from three administrative regions in Malawi. The information collected focused on
      the communication that pregnant women had with healthcare providers, their
      perception of that communication, and the barriers to effective communication. A
      thematic approach was used for data analysis. RESULTS: The main themes that
      emerged regarding the nature of communication between healthcare providers and
      patients were: 1) good healthcare provider-patient interaction; 2) verbal abuse
      and lack of respect; 3) failure by healthcare providers to answer or entertain
      questions; 4) linguistic barriers to communication and lack of competency in non
      verbal communication; and 5) discrimination due to one's status. CONCLUSION: This
      study has revealed the existence of some communication barriers such as
      disrespecting and verbally abusing pregnant women, language limitations by some
      healthcare providers and discrimination due to one's status which are affecting
      maternal service delivery in some health facilities in Malawi. The study has also
      shown that pregnant women who are happy with the way healthcare providers
      communicate with them have the motivation to deliver at a health facility. There
      is a need, therefore, to develop an intervention that could help healthcare
      providers to communicate better with their patients.

PMID- 30103768
TI  - Favorable course of previously undiagnosed Methylmalonic Aciduria with
      Homocystinuria (cblC type) presenting with pulmonary hypertension and aHUS in a
      young child: a case report.
AB  - BACKGROUND: Cobalamin C (cblC) defect is the most common inborn error of Vitamin
      B12 metabolism often causing severe neurological, renal, gastrointestinal and
      hematological symptoms. Onset with pulmonary hypertension (PAH) and atypical
      hemolytic-uremic syndrome (aHUS) is rare. CASE PRESENTATION: We describe the case
      of a 2-years old child, previously in good health, admitted to the hospital with
      severe respiratory symptoms, rapid worsening of clinical conditions, O2
      desaturation and palmo-plantar edema. The patient showed PAH and laboratory
      findings compatible with aHUS. cblC defect, an inborn error of metabolism, was
      identified as the cause of all the symptoms described (cardiac, respiratory and
      renal involvement). Results of neonatal screening for inborn errors of metabolism
      had been negative. Administration of IM OHCbl (intramuscular hydroxocobalamin),
      oral betaine and symptomatic treatment with diuretics and anti-hypertensive
      systemic and pulmonary drugs induced dramatic improvement of both cardiac and
      systemic symptoms. CONCLUSIONS: In this case of cblC defect the metabolic
      treatment completely reverted symptoms of aHUS and PAH. The course was favorable,
      and the prognosis is what we foresee for the future.

PMID- 30103769
TI  - The plasticity of primary microglia and their multifaceted effects on endogenous
      neural stem cells in vitro and in vivo.
AB  - BACKGROUND: Microglia-the resident immune cells of the brain-are activated after
      brain lesions, e.g., cerebral ischemia, and polarize towards a classic "M1" pro
      inflammatory or an alternative "M2" anti-inflammatory phenotype following
      characteristic temporo-spatial patterns, contributing either to secondary tissue
      damage or to regenerative responses. They closely interact with endogenous neural
      stem cells (NSCs) residing in distinct niches of the adult brain. The current
      study aimed at elucidating the dynamics of microglia polarization and their
      differential effects on NSC function. RESULTS: Primary rat microglia in vitro
      were polarized towards a M1 phenotype by LPS, or to a M2 phenotype by IL4, while
      simultaneous exposure to LPS plus IL4 resulted in a hybrid phenotype expressing
      both M1- and M2-characteristic markers. M2 microglia migrated less but exhibit
      higher phagocytic activity than M1 microglia. Defined mediators switched
      microglia from one polarization state to the other, a process more effective when
      transforming M2 microglia towards M1 than vice versa. Polarized microglia had
      differential effects on the differentiation potential of NSCs in vitro and in
      vivo, with M1 microglia promoting astrocytogenesis, while M2 microglia supported
      neurogenesis. Regardless of their polarization, microglia inhibited NSC
      proliferation, increased NSC migration, and accelerated NSC differentiation.
      CONCLUSION: Overall, this study shed light on the complex conditions governing
      microglia polarization and the effects of differentially polarized microglia on
      critical functions of NSCs in vitro and in vivo. Refining the understanding of
      microglia activation and their modulatory effects on NSCs is likely to facilitate
      the development of innovative therapeutic concepts supporting the innate
      regenerative capacity of the brain.

PMID- 30103770
TI  - De novo transcriptomic assembly and mRNA expression patterns of Botryosphaeria
      dothidea infection with mycoviruses chrysovirus 1 (BdCV1) and partitivirus 1
      (BdPV1).
AB  - BACKGROUND: Pear ring rot, caused by Botryosphaeria species, is responsible for
      substantial economic losses by causing severe recession of pear tree growth in
      China. Mycovirus-mediated hypovirulence in plant pathogenic fungi is a crucial
      biological method to control fungal diseases. METHODS: We conducted a large-scale
      and comprehensive transcriptome analysis to identify mRNA in B. dothidea in
      response to mycovirus. De novo sequencing technology from four constructed
      libraries of LW-C (Botryosphaeria dothidea chrysovirus 1, BdCV1), LW-P
      (Botryosphaeria dothidea partitivirus 1, BdPV1), LW-CP (LW-1 strain infection
      with BdCV1 and BdPV1), and Mock (free virus) was used to investigate and compare
      gene expression changes in B.dothidea strains infected with mycovirus. RESULTS:
      In total, 30,058 Unigenes with an average length of 2128 bp were obtained from 4
      libraries of B. dothidea strains. These were annotated to specify their
      classified function. We demonstrate that mRNAs of B. dothidea strains in response
      to mycovirus are differentially expressed. In total, 5598 genes were up-regulated
      and 3298 were down-regulated in the LW-CP group, 4468 were up-regulated and 4291
      down-regulated in the LW-C group, and 2590 were up-regulated and 2325 down
      regulated in the LW-P group. RT-qPCR was used to validate the expression of 9
      selected genes. The B. dothidea transcriptome was more affected by BdCV1
      infection than BdPV1. We conducted GO enrichment analysis to characterize gene
      functions regulated by B. dothidea with mycovirus infection. These involved
      metabolic process, cellular process, catalytic activity, transporter activity,
      signaling, and other biological pathways. KEGG function analysis demonstrated
      that the enriched differentially expressed genes are involved in metabolism,
      transcription, signal transduction, and ABC transport. mRNA is therefore involved
      in the interaction between fungi and mycovirus. In addition, changes in
      differential accumulation levels of cp and RdRp of BdCV1 and BdPV1 in B. dothidea
      strains were evaluated, revealing that the accumulation of BdCV1 and BdPV1 is
      related to the phenotype and virulence of B. dothidea strain LW-1. CONCLUSIONS:
      The identification and analysis of mRNAs from B. dothidea was first reported at
      the transcriptome level. Our analysis provides further insight into the
      interaction of B. dothidea strains infection with chrysovirus 1 (BdCV1) and
      partitivirus 1 (BdPV1) at the transcriptome level.

PMID- 30103771
TI  - Protocol for serum exosomal miRNAs analysis in prostate cancer patients treated
      with radiotherapy.
AB  - BACKGROUND: Circulating exosomes from prostate cancer (PCa) patients undergoing
      radiotherapy are attractive candidate biomarkers for monitoring treatment
      response. Multiple workflows for isolation and content characterization of
      exosomes in biofluids have been attempted. We report a protocol to isolate and
      characterize exosomal miRNAs content and assess radiation-induced changes.
      METHODS: In this pilot study, we performed targeted exosomal miRNA profiling of
      25 serum samples obtained from PCa patients with intermediate- and high-risk
      disease treated with curative radiotherapy (RT), and controls. Post-treatment
      blood samples were collected at least 28 days after radiation therapy as a paired
      follow-up sample. The complete workflow consisted of two phases: I) filtration
      and polyethylene glycol salt precipitation phase which enriched particles below
      200 nm in size followed by characterization using electron microscopy, and II)
      flow cytometry. Finally, miRNA expression analysis between untreated and treated
      patient samples was performed using RNA extraction kit, and qRT-PCR. RESULTS: In
      our preliminary data, 1 ml of serum from PCa patients showed higher exosomal
      concentration (3.68E+10) compared to controls (6.07E+08). The overall expression
      of exosomes after RT was found to be higher compared to untreated samples; the
      median value changed from 3.68E+10 to 5.40E+10; p = 0.52. Using electron
      microscopy, we were able to visualize cup-shaped vesicles with morphology and
      size compatible with exosomes. The bead-based flow cytometry showed positivity
      for exosomal tetraspanins surface markers CD63 and CD9. All five miRNAs (hsa-let
      7a-5p, hsa-miR-141-3p, hsa-miR-145-5p, hsa-miR-21-5p, hsa-miR-99b-5p) have been
      identified in exosomes. Despite overall changes in hsa-let-7a-5p expression after
      radiation, the difference was significant only in the high-risk group (p =
      0.037). In addition, the radiation response to hsa-miR-21-5p was elevated in the
      high-risk group compared to the intermediate group (p = 0.036). CONCLUSIONS:
      Herewith, we demonstrated a protocol for isolation of serum exosomes and exosomal
      miRNA amplification. The recovery of exosomal miRNAs and their differential
      expression after radiation treatment suggests promising biomarker potential that
      requires further investigation in larger patient cohorts.

PMID- 30103773
TI  - Cord blood leptin and insulin levels in association with mitochondrial DNA
      content.
AB  - BACKGROUND: The developmental origins of health and disease theory states that a
      disturbance in the early life environment can contribute to disease risk in later
      life. Leptin and insulin are anorectic hormones involved in energy homeostasis
      and are crucial for foetal growth. Disturbances in the levels of these hormones
      contribute to obesity and diabetes. In adults, altered mitochondrial function is
      an important hallmark of metabolic disorders, including obesity and diabetes.
      However, the mitochondrial effects of early life metabolic variation are
      unexplored. We investigated whether there is an association between metabolic
      hormones and mitochondrial DNA (mtDNA) content in early life. METHODS: The study
      included 236 newborns from the FLEHS III birth cohort, Flanders (Belgium).
      Relative mtDNA content of cord blood leukocytes was determined using quantitative
      PCR. Cord blood levels of leptin and insulin were determined using immunoassays.
      We studied the association between these metabolic hormones and mtDNA content
      using multiple linear regression models, while accounting for covariates and
      potential confounders. RESULTS: Leptin and insulin levels were positively
      associated with cord blood mtDNA content. mtDNA content was respectively 4.49%
      (95% CI 1.15-7.93; p = 0.008) and 1.60% (95% CI 0.31-2.91; p = 0.02) higher for a
      interquartile range increase of respectively cord blood leptin and insulin
      levels. In a sensitivity analysis, we observed that insulin and leptin were
      independently associated to mtDNA content and that insulin was stronger
      associated to mtDNA content in boys than in girls. CONCLUSION: Neonatal metabolic
      hormones were associated with cord blood mtDNA content, which suggests that in
      early life the variation of mtDNA content might accommodate or reflect changes in
      the metabolic status.

PMID- 30103772
TI  - RAS modulation prevents progressive cognitive impairment after experimental
      stroke: a randomized, blinded preclinical trial.
AB  - BACKGROUND: With the aging population, the prevalence and incidence of
      cerebrovascular disease will continue to rise, as well as the number of
      individuals with vascular cognitive impairment/dementia (VCID). No specific FDA
      approved treatments for VCID exist. Although clinical evidence supports that
      angiotensin receptor blockers (ARBs) prevent cognitive decline in older adults,
      whether ARBs have a similar effect on VCID after stroke is unknown. Moreover,
      these agents reduce BP, which is undesirable in the acute stroke period, so we
      believe that giving C21 in this acute phase or delaying ARB administration would
      enable us to achieve the neurovascular benefits without the risk of unintended
      and potentially dangerous, acute BP lowering. METHODS: The aim of our study was
      to determine the impact of candesartan (ARB) or compound-21 (an angiotensin type
      2 receptor--AT2R--agonist) on long-term cognitive function post-stroke, in
      spontaneously hypertensive rats (SHRs). We hypothesized that AT2R stimulation,
      either directly with C21, or indirectly by blocking the angiotensin type 1
      receptor (AT1R) with candesartan, initiated after stroke, would reduce cognitive
      impairment. Animals were subjected to a 60-min transient middle cerebral artery
      occlusion and randomly assigned to either saline/C21 monotherapy, for the full
      study duration (30 days), or given sequential therapy starting with saline/C21 (7
      days) followed by candesartan for the remainder of the study (21 days). Outcome
      measures included sensorimotor/cognitive-function, amyloid-beta determination,
      and histopathologic analyses. RESULTS: Treatment with RAS modulators effectively
      preserved cognitive function, reduced cytotoxicity, and prevented chronic
      reactive microgliosis in SHRs, post-stroke. These protective effects were
      apparent even when treatment was delayed up to 7 days post-stroke and were
      independent of blood pressure and beta-amyloid accumulation. CONCLUSION:
      Collectively, our findings demonstrate that RAS modulators effectively prevent
      cognitive impairment after stroke, even when treatment is delayed.

PMID- 30103774
TI  - Optimized radiotherapy to improve clinical outcomes for locally advanced lung
      cancer.
AB  - BACKGROUND: We aimed to evaluate the toxicity, loco-regional control (LRC) and
      overall survival (OS) associated with accelerated intensity-modulated
      radiotherapy (IMRT) for locally advanced lung cancer. METHODS: Seventy-three
      patients were consecutively treated with IMRT from November 2011 to August 2016.
      A total dose of 66 Gy was delivered using two different schedules of
      radiotherapy: simultaneous modulated accelerated radiotherapy (SMART) (30 * 2.2
      Gy, across 6 weeks) with or without chemotherapy, or moderate hypofractionated
      radiotherapy (HRT) (24 * 2.75 Gy, across 4 weeks) in patients unfit to receive
      concomitant chemotherapy. Data on esophageal and pulmonary toxicities, LRC and OS
      were prospectively collected. RESULTS: The median follow-up duration was 44
      months. Severe pneumonitis and esophagitis (grade 3-4) were observed in 7% and 1%
      of patients respectively, with only one case of grade 4 (pneumonitis). Overall,
      the 1-year and 2-year LRCs were 76% [95 confidence interval (CI)%: 66-87%] and
      62% [95 CI%: 49-77%] respectively. The 1 and 2-year OS rates were 72% [95% CI: 63
      83%] and 54% [95 CI%: 43-68%] respectively. None parameters were correlated with
      LRC or OS. In particular, no difference was observed between patients treated
      with SMART and H-RT (p = 0.26 and 0.6 respectively), with a 1-year LRC of 74% [95
      CI%: 62-86%] for SMART and 91% [95 CI%: 74-100%] for H-RT. No significant
      differences were observed in the toxicity rates associated with each of the RT
      schedules. CONCLUSIONS: Accelerated IMRT for locally advanced lung cancer is
      associated with low toxicities and high LRC. Moderate hypofractionated RT, by
      decreasing the total treatment time, may be promising in improving clinical
      outcomes.

PMID- 30103775
TI  - Recombination of a dual-CAR-modified T lymphocyte to accurately eliminate
      pancreatic malignancy.
AB  - BACKGROUND: The therapeutic application of T cells endowing with chimeric antigen
      receptors (CARs) is faced with "on-target, off-tumor" toxicity against solid
      tumors, particularly in the treatment of the pancreatic cancer. To our best
      knowledge, the pancreatic cancer cell line AsPC-1 often highly expressed some
      distinct tumor-associated antigens, such as carcino-embryonic antigen (CEA) and
      mesothelin (MSLN). Therefore, in this research, we have characterized dual
      receptor CAR-modified T cells (dCAR-T) that exert effective and safe cytotoxicity
      against AsPC-1 cells. METHODS: Based on the dual signaling pathway of wild T
      cells, we designed a novel dCAR diagram specific for CEA and MSLN, which achieved
      comparable activity relative to that of conventional CAR-T cells (CEA-CAR T or
      MSLN-CAR T). In this dCAR, a tandem construct containing two physically separate
      structures, CEA-CD3zeta and MSLN-4/1BB signaling domains were effectively
      controlled with tumor antigens CEA and MSLN, respectively. Finally, the activity
      of dCAR-T cells has been verified via in vitro and in vivo experiments. RESULTS:
      In the presence of cognate tumor cells (AsPC-1) expressing both CEA and MSLN,
      dCAR-T cells exerted high anti-tumor activity relative to that of other single
      receptor CAR-T cells bearing only one signaling pathway (e.g., Czeta-CAR and MBB
      CAR). In a xenograft model, dCAR-T cells significantly inhibited the growth of
      AsPC-1 cells yet no effect on the growth of non-cognate tumor cells. Furthermore,
      the released cytokines and T cell persistence in mice were comparable with that
      of conventional CAR-T cells, obtaining specific and controllable cytotoxicity.
      CONCLUSIONS: A novel type of CAR-T cells, termed dCAR-T, was designed with
      specific activities, that is, significant cytotoxicity for two antigen-positive
      tumor cells yet no cytotoxicity for single antigen-positive tumor cells. Dual
      targeted CAR-T cells can be precisely localized at the tumor site and can exert
      high cytotoxicity against tumor cells, alleviating "on-target, off-tumor"
      toxicity and enabling accurate application of CAR-T cell therapy.

PMID- 30103777
TI  - The efficacy and safety of platelet-rich fibrin for rotator cuff tears: a meta
      analysis.
AB  - BACKGROUND: The aim of this meta-analysis was to evaluate the efficacy and safety
      of platelet-rich fibrin (PRF) in improving clinical outcomes in rotator cuff
      tears. METHODS: We searched the following databases: Pubmed, Embase, and Cochrane
      library databases from inception to April 2018. Studies that compared platelet
      rich fibrin versus placebo for rotator cuff tears were included in this meta
      analysis. Risk ratio (RR) with 95% confidence interval (CI) was pooled for
      discontinuous outcome, and weighted mean difference (WMD) with 95% CI was pooled
      for continuous outcome. Stata 12.0 was used for meta-analysis. RESULTS: A total
      of eight studies with 219 patients were finally included in this meta-analysis.
      Compared with the control group, PRF has a negative role in reducing the re-tear
      rate (RR = 1.30, 95% CI = 0.97 to 1.75; P = 0.082). Subgroup analysis of re-tear
      rate was consistent in all subgroup analyses (single row or double row, volume,
      and risk of bias). There was no significant difference between the American
      Shoulder and Elbow Surgeons scale, University of California at Los Angeles scale,
      Constant score, and side effect (P > 0.05). CONCLUSION: In conclusion, our meta
      analysis suggests that the PRF does not have better effect on improving the
      overall clinical outcomes and re-tear rate in the arthroscopic repair of rotator
      cuff tears.

PMID- 30103776
TI  - Reducing violence against children by implementing the preventative intervention
      Interaction Competencies with Children for Teachers (ICC-T): study protocol for a
      cluster randomized controlled trial in Southwestern Uganda.
AB  - BACKGROUND: An adolescent's school is often the second most important place for
      his development and education after the home. However, reports highlight the
      recurrence of the use of violent discipline in schools. There are few school
      based interventions that aim at reducing violence at school that have been
      implemented and evaluated in sub-Saharan Africa. To reduce violent disciplinary
      measures used at school, we aim to implement and evaluate the feasibility and
      efficacy of the preventative intervention Interaction Competencies with Children
      for Teachers (ICC-T). METHODS/DESIGN: The study will be conducted in six randomly
      selected districts of the Ankole region in southwestern Uganda. We shall randomly
      select two mixed-day secondary schools from each district that fulfill our
      inclusion criteria. Schools will be randomly assigned to the intervention
      condition, where ICC-T will be implemented, and control schools (no
      intervention). Sixty students between the ages of 12 and 17 years and at least 15
      teachers per school will be included in the trial. We aim to collect pre
      assessment data directly before the intervention (t1) and 3 months after the
      intervention (t2) in both intervention and control schools. Using self
      administered questionnaires, we will measure students' exposure to violence using
      the Conflict Tactics Scale (CTS), their psychological well-being using the
      Strengths and Difficulties Questionnaire (SDQ), and teachers' positive attitudes
      towards violent disciplining and teachers' use of violent disciplinary methods
      (CTS). The implementation feasibility of ICC-T in the cultural context of
      southwestern Uganda will be assessed with purpose-built measures that follow the
      guidelines for feasibility studies assessing the demand, applicability,
      acceptability, and integration of core elements in the daily work. DISCUSSION:
      The proposed study will allow us to test the feasibility and efficacy of a
      preventative intervention seeking to reduce violent disciplinary measures in
      school settings using a scientifically rigorous design. The proposed study
      provides the opportunity to contribute to the attainment of goal number 16.2 of
      the United Nations' Sustainable Development Agenda 2015-2030, which aspires to
      end all forms of violence against children. TRIAL REGISTRATION:
      ClinicalTrials.gov, NCT03051854 . Registered on 14 February 2017.

PMID- 30103778
TI  - Advancing the science behind human resources for health: highlights from the
      Health Policy and Systems Research Reader on Human Resources for Health.
AB  - Health workers are central to people-centred health systems, resilient economies
      and sustainable development. Given the rising importance of the health workforce,
      changing human resource for health (HRH) policy and practice and recent health
      policy and systems research (HPSR) advances, it is critical to reassess and
      reinvigorate the science behind HRH as part of health systems strengthening and
      social development more broadly. Building on the recently published Health Policy
      and Systems Research Reader on Human Resources for Health (the Reader), this
      commentary reflects on the added value of HPSR underpinning HRH. HPSR does so by
      strengthening the multi-disciplinary base and rigour of HRH research by (1)
      valuing diverse research inferences and (2) deepening research enquiry and
      quality. It also anchors the relevance of HRH research for HRH policy and
      practice by (3) broadening conceptual boundaries and (4) strengthening policy
      engagement. Most importantly, HPSR enables us to transform HRH from being
      faceless numbers or units of health producers to the heart and soul of health
      systems and vital change agents in our communities and societies. Health workers'
      identities and motivation, daily routines and negotiations, and training and
      working environments are at the centre of successes and failures of health
      interventions, health system functioning and broader social development. Further,
      in an increasingly complex globalised economy, the expansion of the health sector
      as an arena for employment and the liberalisation of labour markets has
      contributed to the unprecedented movement of health workers, many or most of whom
      are women, not only between public and private health sectors, but also across
      borders. Yet, these political, human development and labour market realities are
      often set aside or elided altogether. Health workers' lives and livelihoods,
      their contributions and commitments, and their individual and collective agency
      are ignored. The science of HRH, offering new discoveries and deeper
      understanding of how universal health coverage and the Sustainable Development
      Goals are dependent on millions of health workers globally, has the potential to
      overcome this outdated and ineffective orthodoxy.

PMID- 30103779
TI  - Comparative 1D Blue-Native electrophoresis analysis of Plasmodium falciparum and
      human proteins associated with cytoadherence.
AB  - BACKGROUND: To understand more about changes to the molecular components that
      occur when host endothelium interacts with Plasmodium falciparum-infected
      erythrocytes, a combined technique of protein separation (1D Blue-Native
      electrophoresis) and mass spectrometry of infected erythrocytes with endothelial
      cells (EC) in a co-culture system has been used. METHODS: Native proteins were
      extracted from co-cultures and identified by mass spectrometry. Proteomic data
      from different parasite strains, either adhesion proficient (to endothelial
      cells) or non-adherent, were analysed in parallel to reveal protein associations
      linked to cytoadherence. Informatic approaches were developed to facilitate this
      comparison. RESULTS: Blue-Native gel separation and LC/MS/MS identification
      revealed major differences in samples produced from endothelial cell co-culture
      with adherent and non-adherent parasite strains. This approach enabled us to
      identify protein associations seen only with the adhesion proficient parasite
      strain. CONCLUSIONS: The combination of proteomic and analytical approaches has
      identified differences between adherent and non-adherent parasite lines in co
      culture with EC, providing potential candidates for complexes or associations
      formed during cytoadherence involved in cell structure, signalling and apoptosis.

PMID- 30103780
TI  - EGFR T790M detection and osimertinib treatment response evaluation by liquid
      biopsy in lung adenocarcinoma patients with acquired resistance to first
      generation EGFR tyrosine kinase inhibitors.
AB  - BACKGROUND: Lung adenocarcinoma with EGFR activating mutations will inevitably
      acquire resistance to first generation TKIs. Acquired EGFR T790M mutation causes
      about 50% of these resistance cases. Droplet digital PCR (ddPCR) and cobas
      enables quantification of T790M mutation. Whether these methods can predict
      clinical response of osimertinib treatment is unknown. METHODS: Tumor and blood
      samples from 69 stage IIIB-IV NSCLC patients acquired resistance to EGFR-TKI were
      collected. Cobas(r) Mutation Test v2 kit was used to detect EGFR mutations in
      FFPE or plasma samples. Plasma T790M mutation of both osimertinib naive and
      treated patients were quantified by Droplet digital PCR (ddPCR). RESULTS: T790M
      mutation rate detected by FFPE tissue cobas, plasma ctDNA cobas and plasma ctDNA
      ddPCR test were 54.5, 21.3 and 30.4% respectively. The T790M positive rate was
      52.2% considering all testing methods. The objective response rate (ORR) was
      60.9% in 23 patients received osimertinib treatment. Quantification of T790M
      after treatment decreased to very low level, but no association was observed
      between clinical response and T790M mutation level decrease. CONCLUSION: ddPCR is
      more sensitive in plama ctDNA testing and should be performed even in tumor
      tissue T790M test negative cases. EGFR T790M mutation level is not associated
      with clinical response after osimertinib treatment.

PMID- 30103781
TI  - MKRN2 inhibits migration and invasion of non-small-cell lung cancer by negatively
      regulating the PI3K/Akt pathway.
AB  - BACKGROUND: Makorin RING zinc finger-2 (MKRN2) belongs to the makorin RING zinc
      finger family and is a novel ubiquitin E3 ligase targeting the p65 subunit of NF
      kappaB to negatively regulate inflammatory responses; however, the relationship
      between MKRN2 and tumorigenesis remains unclear. In this study, we clarified the
      role of MKRN2 in non-small cell lung cancer (NSCLC). METHODS: Tumor specimens
      collected from 261 NSCLC patients from 2013 to 2017 were retrieved from the
      Pathology Archive of the First Affiliated Hospital of China Medical University,
      and we performed assays to evaluate MKRN2 expression and to determine the impact
      of MKRN2 silencing and overexpression on NSCLC-cell migration and invasion.
      RESULTS: We demonstrated that MKRN2 expression was associated with lymph node
      metastasis, p-TNM stage, cancer-cell differentiation, and poor prognosis. By
      altering the expression of MKRN2 in selected cell lines, we found that MKRN2
      inhibited cell migration and invasion through downregulation of the PI3K/Akt
      pathway. CONCLUSIONS: These results suggested that MKRN2 inhibited NSCLC
      progression by reducing the metastatic potential of cancer cells. Our findings
      provide critical insight into the association of MKRN2 expression with favorable
      clinicopathological characteristics in NSCLC patients and suggested that MKRN2
      plays a role in inhibiting NSCLC development.

PMID- 30103782
TI  - Cutaneous epithelioid angiomatous nodule: a report of a series including a case
      with moderate cytologic atypia and immunosuppression.
AB  - BACKGROUND: Cutaneous epithelioid angiomatous nodule (CEAN) is a very rare and
      relatively recently recognized vascular proliferation characterized usually by
      minimal cytological atypia and accompanying mitotic activity. As such, CEAN
      represents an important diagnostic pitfall, which could lead to significant
      misdiagnosis and unnecessary treatment. METHODS: The clinicopathologic findings
      of 5 cases of CEAN were reviewed including a unique case with typical findings
      but also moderate cytologic atypia and brisk mitotic activity in a patient on
      immunosuppression. RESULTS: The cases were in 3 women and 2 men ranging in age
      from 18 to 61 years with lesions in the neck (2 cases), upper arm, back and
      shoulder. In 4 of the cases, the patients did not have any relevant potentially
      contributory clinical history, and in 1 case the patient was on immunosuppressive
      treatment. All 5 cases were superficially located within the dermis, well
      circumscribed and similarly composed of epithelioid cells displaying minimal (in
      4 cases) and moderate (1 case) atypia. The mitotic count ranged from 1 to 3 per
      10 high power fields (HPF) in 4 cases and up to 9 per 10 HPF in the
      immunosuppressed patient. Atypical mitoses were not encountered in any of the
      cases. Two lesions that were incompletely excised recurred, but none of the
      patients showed distant metastases. CONCLUSION: While cytologically alarming,
      CEAN has a characteristic microscopic appearance and if completely excised
      follows an indolent course.

PMID- 30103783
TI  - Rotator cuff tear healing process with graft augmentation of fascia lata in a
      rabbit model.
AB  - BACKGROUND: Fascia lata augmentation of massive rotator cuff tears has shown good
      clinical results. However, its biological effect during the early healing process
      is not clearly understood. The purpose of the study was to evaluate the
      biological efficacy of fascia lata augmentation during the early healing process
      of rotator cuff tears using a rabbit rotator cuff defect model. METHODS: The
      infraspinatus tendon was resected from the greater tuberosity of a rabbit to
      create a rotator cuff tear. The tendon edge was directly sutured to the humeral
      head. The rotator cuff repaired site was augmented with a fascia lata autograft
      (augmentation group, group A). The rotator cuff defect in the contralateral
      shoulder was repaired without augmentation (reattachment group, group R). A group
      with intact rotator cuff was set as the control group. Histological examinations
      and mechanical analysis were conducted 4 and 8 weeks postoperatively. RESULTS: In
      the HE staining, the tendon maturing score of group A was higher than that of
      group R at 4 weeks postoperatively. In the safranin O staining, proteoglycan
      staining at the repaired enthesis in group A at 4 weeks postoperatively was
      stronger than that in group R. Picrosirius red staining showed that type III and
      type I collagen in group A was more strongly expressed than that in group R at 4
      weeks postoperatively. The ultimate failure load of the infraspinatus tendon
      humeral head complex in group A was statistically higher than that in group R at
      4 weeks postoperatively. The ultimate failure load of group A was similar to that
      of the control group. CONCLUSION: The biological and mechanical contribution of
      fascia lata augmentation for massive rotator cuff tears was analyzed in this
      study. Type III collagen was reported to be expressed during the tendon healing
      process. Although the biological action similar to natural ligament healing
      occurred around the fascia lata grafts, type III collagen was gradually replaced
      by type I collagen as the tissue matured. Our results suggest that fascia lata
      augmentation could stimulate biological healing and provide initial fixation
      strength of the repaired rotator cuff.

PMID- 30103785
TI  - Balancing ACT: evaluating the effectiveness of psychoeducation and Acceptance and
      Commitment Therapy (ACT) groups for people with bipolar disorder: study protocol
      for pilot randomised controlled trial.
AB  - BACKGROUND: Bipolar disorder is a chronic and disabling psychiatric condition,
      characterised by recurrent episodes of mania, hypomania and depression. It places
      a heavy burden on sufferers and families, with high societal and healthcare
      costs. Many service users with a diagnosis of bipolar disorder also experience
      prominent psychotic symptoms, with differential diagnoses of schizoaffective
      disorder, and relapses characterised by repeated manic psychotic episodes and
      grandiosity. Such presentations require specific adaptations to standard bipolar
      disorder interventions in order to address their psychosis, alongside mood
      regulation, with a particular emphasis on impulsivity, irritability,
      disinhibition and elation. The Balancing ACT study aims to evaluate an innovative
      group intervention combining Acceptance and Commitment Therapy and
      psychoeducation approaches (ACT/PE) with individuals experiencing bipolar
      disorder and/or symptoms within community psychosis services. METHODS: The
      Balancing ACT study is a randomised controlled trial comparing Balancing ACT
      groups (ACT/PE) plus routine care to routine care alone. Balancing ACT (ACT/PE)
      comprises ten group sessions, each lasting 2 hours, delivered weekly. The primary
      outcome is psychological wellbeing; secondary outcomes are mental health relapses
      (measured by service use averages for the 12 months pre baseline and 3 months
      post baseline). We will also measure mood, distress, recovery and psychological
      change processes. Participants will be randomised in a 1:1 ratio, after baseline
      assessment. Outcomes will be assessed by trained assessors blind to treatment
      condition at 0, 10 and 14 weeks. Recruitment began in April 2017 and is on-going
      until the end of October 2017. DISCUSSION: The Balancing ACT study will
      contribute to the currently limited evidence base for psychological interventions
      for people experiencing bipolar disorder and/or symptoms in the context of
      community psychosis services. TRIAL REGISTRATION: ISRCTN73327972 . Registered on
      27 March 2017. Balancing ACT: evaluating the effectiveness of psychoeducation and
      Acceptance and Commitment Therapy (ACT) groups for people with bipolar disorder.

PMID- 30103784
TI  - Exploring causality in the association between circulating 25-hydroxyvitamin D
      and colorectal cancer risk: a large Mendelian randomisation study.
AB  - BACKGROUND: Whilst observational studies establish that lower plasma 25
      hydroxyvitamin D (25-OHD) levels are associated with higher risk of colorectal
      cancer (CRC), establishing causality has proven challenging. Since vitamin D is
      modifiable, these observations have substantial clinical and public health
      implications. Indeed, many health agencies already recommend supplemental vitamin
      D. Here, we explore causality in a large Mendelian randomisation (MR) study using
      an improved genetic instrument for circulating 25-OHD. METHODS: We developed a
      weighted genetic score for circulating 25-OHD using six genetic variants that we
      recently reported to be associated with circulating 25-OHD in a large genome-wide
      association study (GWAS) meta-analysis. Using this score as instrumental variable
      in MR analyses, we sought to determine whether circulating 25-OHD is causally
      linked with CRC risk. We conducted MR analysis using individual-level data from
      10,725 CRC cases and 30,794 controls (Scotland, UK Biobank and Croatia). We then
      applied estimates from meta-analysis of 11 GWAS of CRC risk (18,967 cases; 48,168
      controls) in a summary statistics MR approach. RESULTS: The new genetic score for
      25-OHD was strongly associated with measured plasma 25-OHD levels in 2821 healthy
      Scottish controls (P = 1.47 * 10- 11), improving upon previous genetic
      instruments (F-statistic 46.0 vs. 13.0). However, individual-level MR revealed no
      association between 25-OHD score and CRC risk (OR 1.03/unit log-transformed
      circulating 25-OHD, 95% CI 0.51-2.07, P = 0.93). Similarly, we found no evidence
      for a causal relationship between 25-OHD and CRC risk using summary statistics MR
      analysis (OR 0.91, 95% CI 0.69-1.19, P = 0.48). CONCLUSIONS: Despite the scale of
      this study and employing an improved score capturing more of the genetic
      contribution to circulating 25-OHD, we found no evidence for a causal
      relationship between circulating 25-OHD and CRC risk. Although the magnitude of
      effect for vitamin D suggested by observational studies can confidently be
      excluded, smaller effects sizes and non-linear relationships remain plausible.
      Circulating vitamin D may be a CRC biomarker, but a causal effect on CRC risk
      remains unproven.

PMID- 30103786
TI  - Upcoming imaging concepts and their impact on treatment planning and treatment
      response in radiation oncology.
AB  - For 2018, the American Cancer Society estimated that there would be approximately
      1.7 million new diagnoses of cancer and about 609,640 cancer-related deaths in
      the United States. By 2030 these numbers are anticipated to exceed a staggering
      21 million annual diagnoses and 13 million cancer-related deaths. The three
      primary therapeutic modalities for cancer treatments are surgery, chemotherapy,
      and radiation therapy. Individually or in combination, these treatment modalities
      have provided and continue to provide curative and palliative care to the myriad
      victims of cancer.Today, CT-based treatment planning is the primary means through
      which conventional photon radiation therapy is planned. Although CT remains the
      primary treatment planning modality, the field of radiation oncology is moving
      beyond the sole use of CT scans to define treatment targets and organs at risk.
      Complementary tissue scans, such as magnetic resonance imaging (MRI) and positron
      electron emission (PET) scans, have all improved a physician's ability to more
      specifically identify target tissues, and in some cases, international guidelines
      have even been issued. Moreover, efforts to combine PET and MR to define solid
      tumors for radiotherapy planning and treatment evaluation are also gaining
      traction.Keeping these advances in mind, we present brief overviews of other up
      and-coming key imaging concepts that appear promising for initial treatment
      target definition or treatment response from radiation therapy.

PMID- 30103787
TI  - Identification and characterization of mushroom body neurons that regulate fat
      storage in Drosophila.
AB  - BACKGROUND: In an earlier study, we identified two neuronal populations, c673a
      and Fru-GAL4, that regulate fat storage in fruit flies. Both populations
      partially overlap with a structure in the insect brain known as the mushroom body
      (MB), which plays a critical role in memory formation. This overlap prompted us
      to examine whether the MB is also involved in fat storage homeostasis. METHODS:
      Using a variety of transgenic agents, we selectively manipulated the neural
      activity of different portions of the MB and associated neurons to decipher their
      roles in fat storage regulation. RESULTS: Our data show that silencing of MB
      neurons that project into the alpha'beta' lobes decreases de novo fatty acid
      synthesis and causes leanness, while sustained hyperactivation of the same
      neurons causes overfeeding and produces obesity. The alpha'beta' neurons oppose
      and dominate the fat regulating functions of the c673a and Fru-GAL4 neurons. We
      also show that MB neurons that project into the gamma lobe also regulate fat
      storage, probably because they are a subset of the Fru neurons. We were able to
      identify input and output neurons whose activity affects fat storage, feeding,
      and metabolism. The activity of cholinergic output neurons that innervating the
      beta'2 compartment (MBON-beta'2mp and MBON-gamma5beta'2a) regulates food
      consumption, while glutamatergic output neurons innervating alpha' compartments
      (MBON-gamma2alpha'1 and MBON-alpha'2) control fat metabolism. CONCLUSIONS: We
      identified a new fat storage regulating center, the alpha'beta' lobes of the MB.
      We also delineated the neuronal circuits involved in the actions of the
      alpha'beta' lobes, and showed that food intake and fat metabolism are controlled
      by separate sets of postsynaptic neurons that are segregated into different
      output pathways.

PMID- 30103788
TI  - Epidemiology of distal radius fracture in Akershus, Norway, in 2010-2011.
AB  - BACKGROUND: Several studies published over the last decade indicate an increased
      incidence of distal radius fractures (DRF). With Norway having one of the highest
      reported incidence of DRFs, we conducted a study to assess the epidemiology of
      DRFs and its treatment in the catchment area of Akershus University Hospital
      (AHUS). METHODS: Patients 16 years or older who presented to AHUS with an acute
      DRF during the years 2010 and 2011 were prospectively recorded and classified
      according to the AO fracture classification system. The mechanism of injury and
      treatment modality were noted. RESULTS: Overall, 1565 patients with an acute DRF
      presented to the institution in 2010-2011, of which 1134 (72%) were women. The
      overall annual incidence was 19.7 per 10,000 inhabitants 16 years or older. Women
      had an exponential increase in incidence after the age of 50, though the
      incidence for both genders peaked after the age of 80 years. There was an even
      distribution between extra- and intra-articular fractures. Falling while walking
      outside was the most common mechanism of injury. Of the 1565 registered, 418
      (26.7%) patients underwent surgery, with a volar locking plate being the
      preferred surgical option in 77% of the cases. CONCLUSION: The overall incidence
      of distal radius fractures was lower in our study than earlier reports from
      Norway. Postmenopausal women had a higher risk of fracture than the other groups,
      and low-energy injuries were most dominant. 26.7% were treated operatively, which
      is higher than earlier reports, and might reflect an increasing preference for
      surgical treatment.

PMID- 30103789
TI  - Dual effect of DLBCL-derived EXOs in lymphoma to improve DC vaccine efficacy in
      vitro while favor tumorgenesis in vivo.
AB  - BACKGROUND: Exosomes derived from tumor cells (TEXs) are involved in both immune
      suppression, angiogenesis, metastasis and anticancer stimulatory, but the
      biological characteristics and role of diffuse large B cell lymphoma (DLBCL)
      derived exosomes have been less investigated. METHODS: Exosomes (EXOs) were
      isolated from OCI-LY3, SU-DHL-16, and Raji cells and biological characteristics
      of EXOs were investigated using electron microscopy, flow cytometry analysis, and
      Western blot analysis. The protein expression of EXOs was determined by an
      antibody array. Next, the communication between EXOs and lymphoma cell, stromal
      cell, dendritic cells (DCs), and T cells was evaluated. Finally, effect of DLBCL
      TEXs on tumor growth in vivo was investigated. RESULTS: We demonstrated that EXOs
      derived from DLBCL cell lines displayed malignancy molecules such as c-Myc, Bcl
      2, Mcl-1, CD19, and CD20. There was a different protein expression pattern
      between DLBCL TEXs and Burkitt lymphoma TEXs. DLBCL TEXs were easily captured by
      DCs and lymphoma cells, and mainly acted as an immunosuppressive mediator,
      evidenced by induction of apoptosis and upregulation of PD-1 in T cells.
      Furthermore, the TEXs stimulated not only cell proliferation, migration of
      stromal cells but also angiogenesis. As a result, the TEXs promoted tumor growth
      in vivo. On other hand, DLBCL TEXs did not induce apoptosis of DCs. After pulsed
      with the TEXs, DCs could stimulate clonal expansion of T cells, increase the
      secretion of IL-6 and TNFalpha, and decrease the production of immunosuppressive
      cytokine IL-4 and IL-10. The T cells from tumor bearing mice immunized by TEX
      were shown to possess superior antilymphoma potency relative to immunization of
      tumor lysates. CONCLUSIONS: This study provides the framework for novel
      immunotherapies targeting TEXs in DLBCL.

PMID- 30103790
TI  - Hock lesions in dairy cows in freestall herds: a cross-sectional study of
      prevalence and risk factors.
AB  - BACKGROUND: Hock lesions (HL) in dairy cows are a common animal welfare problem
      in modern dairy production with freestall housing systems, but there are no large
      scale studies addressing its epidemiology in Sweden. The aims of this cross
      sectional study were to investigate the prevalence of HL of different severity in
      100 Swedish freestall dairy herds, and to identify cow- and herd-related risk
      factors. Associations between HL and mastitis as well as culling were also
      investigated. RESULTS: In total, 3217 cows from 99 herds were included in the
      statistical analyses. The overall cow prevalence of hair loss on the hock (mild
      HL) was 68% and the prevalence of ulceration or evident swelling of the hock,
      with or without hair loss, (severe HL) was 6%. The within-herd prevalence varied
      among herds, between 23 and 100% for mild HL, and between 0 and 32% for severe
      ones. Breed (higher risk for Swedish Holstein than for Swedish Red) and days in
      milk (higher risk at 181-305 days than at 0-90 days) were cow-related risk
      factors associated with both types of lesions, whereas higher parity and cleaner
      cows were associated only with increased risk of severe HL. A reduced risk for
      mild HL was seen in cows housed on mattresses compared to rubber mats, and in
      cows housed on peat compared to other bedding materials. Also, cows in herds with
      a high proportion of not yet inseminated heifers older than 17 months had a lower
      risk of mild HL than cows in herds with a low proportion. Risk for severe HL was
      lower when cubicles were of recommended width compared to under recommendation,
      for organic production compared to conventional, and when teat dip or no
      treatment after milking was used, compared to teat spray. For both mild and
      severe HL, herringbone milking parlors were associated with higher risk than
      tandem parlors. We found no significant associations between HL and mastitis or
      culling. CONCLUSIONS: The prevalence of HL is high in Swedish dairy herds,
      although most lesions are mild. Several cow- and herd-related risk factors were
      identified and the results can be used to improve recommendations for the
      prevention of HL in Swedish freestall dairy herds.

PMID- 30103791
TI  - Small area estimation of under-5 mortality in Bangladesh, Cameroon, Chad,
      Mozambique, Uganda, and Zambia using spatially misaligned data.
AB  - BACKGROUND: The under-5 mortality rate (U5MR) is an important metric of child
      health and survival. Country-level estimates of U5MR are readily available, but
      efforts to estimate U5MR subnationally have been limited, in part, due to spatial
      misalignment of available data sources (e.g., use of different administrative
      levels, or as a result of historical boundary changes). METHODS: We analyzed all
      available complete and summary birth history data in surveys and censuses in six
      countries (Bangladesh, Cameroon, Chad, Mozambique, Uganda, and Zambia) at the
      finest geographic level available in each data source. We then developed small
      area estimation models capable of incorporating spatially misaligned data. These
      small area estimation models were applied to the birth history data in order to
      estimate trends in U5MR from 1980 to 2015 at the second administrative level in
      Cameroon, Chad, Mozambique, Uganda, and Zambia and at the third administrative
      level in Bangladesh. RESULTS: We found substantial variation in U5MR in all six
      countries: there was more than a two-fold difference in U5MR between the area
      with the highest rate and the area with the lowest rate in every country. All
      areas in all countries experienced declines in U5MR between 1980 and 2015, but
      the degree varied both within and between countries. In Cameroon, Chad,
      Mozambique, and Zambia we found areas with U5MRs in 2015 that were higher than in
      other parts of the same country in 1980. Comparing subnational U5MR to country
      level targets for the Millennium Development Goals (MDG), we find that 12.8% of
      areas in Bangladesh did not meet the country-level target, although the country
      as whole did. A minority of areas in Chad, Mozambique, Uganda, and Zambia met the
      country-level MDG targets while these countries as a whole did not. CONCLUSIONS:
      Subnational estimates of U5MR reveal significant within-country variation. These
      estimates could be used for identifying high-need areas and positive deviants,
      tracking trends in geographic inequalities, and evaluating progress towards
      international development targets such as the Sustainable Development Goals.

PMID- 30103792
TI  - Comparison of early complications between the use of a cannulated screw locking
      plate and multiple cancellous screws in the treatment of displaced intracapsular
      hip fractures in young adults: a randomized controlled clinical trial.
AB  - BACKGROUND: The incidence of early postoperative complications of displaced
      intracapsular hip fractures is high. The purpose of this study was to compare the
      early postoperative complications and assess the incidence of femoral neck
      shortening on using a newly designed proximal femoral cannulated screw locking
      plate (CSLP) versus multiple cancellous screws (MCS) in the treatment of
      displaced intracapsular hip fractures in young adults. METHODS: Sixty-eight young
      adult patients with displaced intracapsular hip fractures were randomly assigned
      to either the CSLP group or the MCS group and treated routinely by internal
      fixation with either the CSLP or the MCS. Harris Hip Score, nonunion, failure of
      fixation, overall complications, and femoral neck shortening were recorded and
      compared. RESULTS: Two patients (5.88%) in the CSLP group and eight (23.53%) in
      the MCS group had postoperative nonunion (P < 0.05). There was one case (2.94%)
      of fixation failure in the CSLP group and three cases (8.82%) in the MCS group (P
      > 0.05). Three patients (8.82%) in the CSLP group and 11 (32.35%) in the MCS
      group had overall complications (P < 0.05). Mean femoral neck shortening was 5.10
      mm in the vertical plane and 5.11 mm in the horizontal plane in the CSLP group
      and 11.14 mm in the vertical plane and 10.51 mm in the horizontal plane in the
      MCS group. Severe femoral neck shortening (>= 10 mm) did not occur in either the
      vertical or the horizontal plane in any patient of the CSLP group but occurred in
      10 patients (28.57%) in the vertical plane and in 8 (22.86%) patients in the
      horizontal plane in the MCS group. CONCLUSIONS: Compared with MCS, the use of
      CSLP in the treatment of displaced intracapsular hip fractures in young adults
      can reduce the rates of postoperative nonunion and overall complications and
      minimize femoral neck shortening. TRIAL REGISTRATION: ChiCTR1800016032 .
      Registered 8 May 2018. Retrospectively registered.

PMID- 30103793
TI  - Impact of tax and subsidy framed messages on high- and lower-sugar beverages sold
      in vending machines: a randomized crossover trial.
AB  - OBJECTIVE: Framing of fiscal incentives has been suggested to be important in
      influencing purchase decisions. We aimed to examine the effect of framing a
      modest price difference between high- and lower-sugar beverages as a tax or a
      subsidy respectively, using messages placed on vending machines to influence
      beverage purchases. DESIGN/SETTING: This is an 11-week randomized crossover trial
      conducted between August and November 2015, with a two-week run-in period before
      intervention, targeted at students, staff and faculty of a university campus in
      Singapore. Twenty-one beverage vending machines were used to implement the
      intervention involving 'tax message', 'subsidy message' and 'no message
      (control)'. The former two messages suggest 'a tax for high sugar beverages' or
      'a subsidy for lower sugar beverages' respectively. Prices of the beverages
      offered were fixed at baseline and remained the same in all three experimental
      conditions: lower-sugar beverage options were priced ~ 10% lower than the
      corresponding high-sugar option. The machines were randomized to one of the 6
      sequences of intervention. Each message intervention period was 3 weeks. The
      effect of messages was assessed by comparing average weekly units of beverages
      sold between interventions using mixed effects model. RESULTS: The average weekly
      units of high and lower-sugar beverages sold per vending machine were 115 and 98
      respectively in the control condition. The percentage of high-sugar beverages
      sold was 54% in the control, 53% in the tax, and 54% in the subsidy message
      condition. There was no difference in the weekly units of high-sugar beverages
      sold for the tax message (- 2, 95% CI -8 to 5, p = 0.61) or the subsidy message
      (0, 95% CI -10 to 10, p = 0.96) conditions as compared with the control
      condition. Similarly, there was no difference in the weekly units of lower-sugar
      beverages sold for the tax message (4, 95% CI -4 to 13, p = 0.32) or the subsidy
      message (7, 95% CI -4 to 18, p = 0.18) conditions as compared with the control
      condition. CONCLUSIONS: The use of tax and subsidy messages to highlight modest
      price differences did not substantially reduce high-sugar beverage sales in
      vending machines on an Asian university campus.

PMID- 30103794
TI  - Connexin 30 deficiency attenuates A2 astrocyte responses and induces severe
      neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride
      Parkinson's disease animal model.
AB  - BACKGROUND: The first pathology observed in Parkinson's disease (PD) is 'dying
      back' of striatal dopaminergic (DA) terminals. Connexin (Cx)30, an astrocytic gap
      junction protein, is upregulated in the striatum in PD, but its roles in
      neurodegeneration remain elusive. We investigated Cx30 function in an acute PD
      model by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to
      wild-type (WT) and Cx30 knockout (KO) mice. METHODS: On days 1 and 7 after MPTP
      administration, we evaluated changes in astrocytic Cx30, Cx43, glial fibrillary
      acidic protein, and ionised calcium-binding adapter molecule 1 expression by
      immunostaining and biochemical analysis. Loss of DA neurons was evaluated by
      tyrosine hydroxylase immunostaining. Gene expression was analysed using A1, A2,
      pan-reactive astrocyte microarray gene sets, and M1, M2, and M1/M2 mixed
      microglial microarray gene sets. Real-time PCR and in situ hybridisation were
      performed to evaluate glial cell-derived neurotrophic factor (Gdnf) and S100a10
      expression. Striatal GDNF protein levels were determined by enzyme-linked
      immunosorbent assay. RESULTS: MPTP treatment induced upregulation of Cx30 and
      Cx43 levels in the striatum of WT and KO mice. DA neuron loss was accelerated in
      Cx30 KO compared with WT mice after MPTP administration, despite no change in the
      striatal concentration of methyl-4-phenylpyridinium+. Astrogliosis in the
      striatum of Cx30 KO mice was attenuated by MPTP, whereas microglial activation
      was unaffected. Microarrays of the striatum showed reduced expression of pan
      reactive and A2 astrocyte genes after MPTP treatment in Cx30 KO compared with WT
      mice, while M1, M2, and M1/M2 mixed microglial gene expression did not change.
      MPTP reduced the number of striatal astrocytes co-expressing Gdnf mRNA and
      S100beta protein or S100a10 mRNA and S100beta protein and also reduced the level
      of GDNF in the striatum of Cx30 KO compared with WT mice. CONCLUSIONS: These
      findings indicate that Cx30 plays critical roles in astrocyte neuroprotection in
      an MPTP PD model.

PMID- 30103796
TI  - Determinants of hypothermia on neonates admitted to the intensive care unit of
      public hospitals of Central Zone, Tigray, Ethiopia 2017: unmatched case-control
      study.
AB  - OBJECTIVE: This study aims to identify determinants of hypothermia in neonates in
      neonatal intensive care unit of public hospitals of Central Zone Tigray, Ethiopia
      in 2017. RESULTS: A total of 88 cases and 176 controls were included in this
      study. Ninety-one percent cases and 86.4% controls were in the 1st week of
      neonate age. Multivariable logistic regression analysis showed that delayed
      initiation of breastfeeding [AOR = 7.23; 95% CI (2.75, 18.99)], low birth weight
      [AOR = 8.51; 95% CI (2.71, 26.73)], preterm [AOR = 3.689; 95% CI (1.359,
      10.012)], low APGAR score at 5th min [AOR = 3.71; 95% CI (1.57, 8.79)], skin to
      skin contact [AOR = 6.23; 95% CI (2.523, 15.358)], night time delivery [AOR =
      6.25; 95% CI (2.58, 15.12)] and bathed within 24 h [AOR = 10.06; 95% CI (3.86,
      26.22)] were independent risk factors of neonatal hypothermia.

PMID- 30103795
TI  - DNA barcoding of blackflies (Diptera: Simuliidae) as a tool for species
      identification and detection of hidden diversity in the eastern regions of Spain.
AB  - BACKGROUND: Blackflies have negative impact on public and animal health due to
      the haematophagous habit of females. In recent times, in some regions in Spain,
      blackfly outbreaks are becoming more and more frequent, threatening the public
      health. However, there is still a paucity of data concerning the Spanish blackfly
      fauna. Correct identification of species is of paramount importance in order to
      provide correct information on species distribution, biology and behaviour, so
      that control measures could be implemented appropriately. METHODS: Blackflies
      specimens (larvae, pupae, reared adults and biting females) were collected in the
      period 2015-2017 in and near rivers and streams from different regions in Spain.
      A modified Hotshot technique was used for the DNA extraction and the cox1 DNA
      barcoding region of the cytochrome c oxidase subunit 1 was sequenced from the
      specimens collected. RESULTS: In total, we collected 239 specimens representing
      22 species. Of these, six species are new records for the Aragon region: P.
      tomosvaryi, S. bertrandi, S. galloprovinciale, S. lineatum, S. rubzovianum and S.
      xanthinum. Cox1 DNA barcode sequences for 21 species were recovered, including
      four species of the genus Prosimulium and 17 species of the genus Simulium
      [Boophthora (1 species), Eusimulium (1 species), Nevermannia (4 species),
      Simulium (s.s.) (6 species), Trichodagmia (1 species) and Wilhelmia (4 species)].
      For the first time the complete DNA barcodes for five species (P. tomosvaryi, S.
      carthusiense, S. brevidens, S. monticola and S. sergenti) were registered. Most
      of the specimens belonging to the same recognized species were clustered together
      in the neighbour-joining tree, except for S. argyreatum, S. monticola and S.
      variegatum. The overall genetic distance in the dataset was 0.14%. The average of
      the intraspecific genetic divergence within the different taxa was 1.47% (0.05
      3.96%). In contrast, the interspecific divergence varied between 2.50-22.0%.
      CONCLUSIONS: In this study we assessed the use of the cox1 DNA barcoding region
      for the identification of species of blackflies in Spain. Our results showed that
      combining DNA barcoding with morphology enhanced our taxonomic rationale in
      identifying the blackflies in the country.

PMID- 30103797
TI  - Soil-transmitted helminth infections, anemia and undernutrition among
      schoolchildren in Yirgacheffee, South Ethiopia.
AB  - OBJECTIVE: Current data on soil-transmitted helminth infections, anemia and
      malnutrition that are largely neglected is vital to the control and management of
      them in a specific setting. This study was, therefore, aimed at determining the
      status of the three health concerns in one of the high-risk groups,
      schoolchildren, in South Ethiopia. RESULTS: Among the 443 sampled schoolchildren,
      54% were infected with soil-transmitted helminths (STHs) and 15.4% of them had
      anaemia, while the prevalence rate of undernutrition was 28.9%. Species-wise,
      prevalence of STH infections was 21.7, 16.7, 7.2 and 8.4% for Ascaris
      lumbricoides, the hookworms, Trichuris trichiura and mixed infections,
      respectively. Untreated drinking water, high frequency of sucking fingernails and
      open defecation were significantly associated with risk of getting STH
      infections. Child positivity for STH infection didn't show any significant
      association with undernutrition of the children. Anaemia was significantly
      correlated with hookworm (adjusted odds ratio (AOR) = 2.96, 95% confidence
      interval (CI) = 2.15, 4.86), A. lumbricoides (AOR = 1.93, 95% CI = 1.13, 3.01)
      and polyparasitism (AOR = 1.54, 95% CI = 1.04, 2.64). In addition, children with
      heavy intensities of hookworm infections and those undernourished were more
      likely to suffer from anaemia with P = 0.001 and P = 0.007, respectively.

PMID- 30103798
TI  - Lactobacillus salivarius reverse antibiotic-induced lung defense impairment in a
      ventilator model.
AB  - BACKGROUND: Widespread use of antibiotics in the intensive care unit is a
      potential cause of the emergence of hospital-acquired pneumonia. This study
      determined whether Lactobacillus salivarius feeding could reverse antibiotic
      induced lung defense impairment in a ventilator model. METHODS: C57BL/6 wild-type
      (WT) mice received mechanical ventilation for 3 h after intramuscular antibiotic
      treatment for 6 days. Treatment with dead Lactobacillus salivarius and fructo
      oligosaccharides (FOS) feeding were used to stimulate antibacterial protein
      expression in the intestine. Reactive oxygen species (ROS) in the intestinal
      mucosa was detected using 2'7'-dichlorofluorescein diacetate. The peroxynitrite
      production of alveolar macrophages (AMs) was measured using dihydrorhodamine 123
      oxidation assay. N-acetylcysteine (NAC), an ROS scavenger, was orally
      administered to mice receiving antibiotics with FOS feeding. RESULTS: Antibiotic
      treatment decreased Pseudomonas aeruginosa (PA) phagocytic activity and activity
      of AMs and protein expression of regenerating islet-derived protein 3beta
      (Reg3beta) as well as Toll-like receptor 4 (TLR4) in the intestinal mucosa in the
      ventilator model. Antibiotic treatment also decreased ROS production in the
      intestinal mucosa, peroxynitrite production of AMs, and RELMbeta expression as
      well as NF-kappaB DNA binding activity of the intestinal mucosa in WT mice but
      not in MyD88-/- mice. Treatment with dead L. salivarius or FOS feeding increased
      ROS production, bacterial killing activity, and protein expression of Reg3beta as
      well as TLR4 in the intestinal mucosa and reversed the inhibitory effects of
      antibiotics on PA phagocytic activity of AMs. CONCLUSION: Taken together with the
      finding that ablation of FOS-induced intestinal ROS using NAC decreased
      peroxynitrite production as well as PA phagocytic activity of AMs and protein
      expression of CRP-ductin, IL-17, Reg3beta, and RELMbeta in the intestinal mucosa,
      we conclude that commensal microflora plays a key role in stimulating lung
      immunity. Intestinal ROS plays a role as a predictive indicator and modulator of
      pulmonary defense mechanisms. Antibiotic treatment reduces lung defense against
      PA infection through the decrease in intestinal Reg3beta and TLR4 expression.
      Treatment with dead L. salivarius or FOS feeding reverses the antibiotic-induced
      lung defense impairment through the intestinal ROS/MyD88 pathways.

PMID- 30103799
TI  - Factors associated with latrine utilization among model and non-model families in
      Laelai Maichew Woreda, Aksum, Tigray, Ethiopia: comparative community based
      study.
AB  - OBJECTIVE: The study was conducted on 313 model and 313 non model households to
      assess latrine utilization and factors affecting among model and non-model
      families. RESULT: About 225 (71.9%) model and 144 (46%) non-model participants
      declared that they utilize their latrine which gave the overall utilization rate
      of 369 (58.9%). Households with primary and above education were two times (AOR =
      2.03, 95% CI 1.427, 4.638) more likely to utilize latrine as compared with
      illiterate households. Cleanness of the latrine was also found to be associated
      with latrine utilization in both model and non-model families. Age, type of
      latrine, latrine supper structure, cleanness and observable soap near the latrine
      in model families and age, educational status, occupation, latrine privacy and
      cleanness in non-model families were identified as a statistical significant
      factor for latrine utilization.

PMID- 30103800
TI  - Establishment of a complex skin structure via layered co-culture of keratinocytes
      and fibroblasts derived from induced pluripotent stem cells.
AB  - BACKGROUND: Skin is an organ that plays an important role as a physical barrier
      and has many other complex functions. Skin mimetics may be useful for studying
      the pathophysiology of diseases in vitro and for repairing lesions in vivo. Cord
      blood mononuclear cells (CBMCs) have emerged as a potential cell source for
      regenerative medicine. Human induced pluripotent stem cells (iPSCs) derived from
      CBMCs have great potential for allogenic regenerative medicine. Further study is
      needed on skin differentiation using CBMC-iPSCs. METHODS: Human iPSCs were
      generated from CBMCs by Sendai virus. CBMC-iPSCs were differentiated to
      fibroblasts and keratinocytes using embryonic body formation. To generate CBMC
      iPSC-derived 3D skin organoid, CBMC-iPSC-derived fibroblasts were added into the
      insert of a Transwell plate and CBMC-iPSC-derived keratinocytes were seeded onto
      the fibroblast layer. Transplantation of 3D skin organoid was performed by the
      tie-over dressing method. RESULTS: Epidermal and dermal layers were developed
      using keratinocytes and fibroblasts differentiated from cord blood-derived human
      iPSCs, respectively. A complex 3D skin organoid was generated by overlaying the
      epidermal layer onto the dermal layer. A humanized skin model was generated by
      transplanting this human skin organoid into SCID mice and effectively healed skin
      lesions. CONCLUSIONS: This study reveals that a human skin organoid generated
      using CBMC iPSCs is a novel tool for in-vitro and in-vivo dermatologic research.

PMID- 30103801
TI  - Are disadvantaged children more likely to be excluded from analysis when applying
      global positioning systems inclusion criteria?
AB  - OBJECTIVE: When using global positioning systems (GPS) to assess an individual's
      exposure to their environment, a first step in data cleaning is to establish
      minimum GPS 'inclusion criteria' (a set of rules used to determine which GPS data
      are able to be included in analyses). Care is needed at this stage to avoid any
      data exclusion (data loss) systematically biasing results in terms of
      characteristics of the environment and participants. The extent of potential
      systematic bias in sample retention due to GPS data loss and application of GPS
      inclusion criteria is unknown. The aim of this study was to describe differences
      in sample size and socio-demographic characteristics of the retained sample when
      applying three different GPS inclusion criteria. The study assessed 7-day GPS
      data collected from children (aged 9-13 years) recruited from nine schools in
      Auckland, New Zealand as part of the Kids in the City study. RESULTS:
      Participants from ethnic minorities and those attending schools in lower
      socioeconomic areas were disproportionately excluded from the retained samples.
      This highlights potential equity implications in basing the assessment of
      exposure-which ultimately influences research results on the relationship between
      environment and health-on non-representative GPS data.

PMID- 30103802
TI  - Clinical and prognostic profile of Her2neu positive (non-luminal) intrinsic
      breast cancer subtype: comparison with Her2neu positive luminal breast cancers.
AB  - OBJECTIVE: Her2neu receptor is proto-oncogene which can be over-expressed in both
      luminal and non-luminal breast cancers. In the present study, we aimed to compare
      the prognostic and predictive factors like tumor grade, T-stage, N-stage and ki67
      index in Her2neu intrinsic breast cancer subtype with Her2neu over-expressed
      luminal breast cancers. RESULTS: 801 (41%) cases were Her2neu positive; out of
      which, 418 cases (52.2%) showed ER positivity and thus were classified as Her2neu
      positive luminal cancers whereas 383 cases (47.8%) were ER and PR negative and
      therefore were labeled as intrinsic Her2neu subtype (non-luminal). Her2neu
      positive (non-luminal) cancers were significantly associated with higher grades
      and Ki67 proliferative index compared to Her2neu positive luminal cancers. On the
      other no significant association was noted in T-stage and N-stage. We found a
      high frequency of her2neu positivity in our studied population of breast cancer.
      Moreover, association of her2neu positive (non-luminal) breast cancers with
      higher grade and ki67 index indicates a predictive value of ER/PR positivity in
      her2neu positive breast cancers. On the other hand, lack of association with
      respect to T and N stage, signifies no prognostic benefit of ER/PR in her2neu
      positive breast cancers.

PMID- 30103803
TI  - Vector competence of pre-alpine Culicoides (Diptera: Ceratopogonidae) for
      bluetongue virus serotypes 1, 4 and 8.
AB  - BACKGROUND: Bluetongue disease, caused by bluetongue virus serotype 8 (BTV-8),
      appeared for the first time in the northern part of Europe in 2006, and
      subsequently rapidly spread causing severe economic losses to the farming
      industry. The implicated vectors of BTV in Europe are Culicoides species within
      the subgenus Avaritia (C. chiopterus, C. dewulfi, C. obsoletus and C. scoticus).
      Epidemiological data from Switzerland have shown that BTV, whose spread was
      eliminated at an early stage by vaccination campaigns, had not been circulating
      among livestock at higher altitudes where other species dominate the Culicoides
      fauna. In this study, we investigated the extent that Culicoides spp. prevailing
      at higher altitudes (mainly C. grisescens) can act as vectors for BTV. METHODS:
      Culicoides were collected at farms in the pre-alpine region (two sites at 1550 m
      above sea level, masl, referred to as pre-alpine I; one site at 2030 masl, pre
      alpine II) and, for comparative purposes, from the Swiss Plateau (one site, 650
      masl). They were fed on bovine blood/BTV suspensions (BTV-1, 4 or 8) and
      incubated for eight days under a fluctuating temperature regime (13-25  degrees
      C, mean 19  degrees C), reflecting a mid-summer warm spell in the pre-alpine
      region. Susceptibility to BTV transmission was assessed from head homogenates by
      RT-qPCR and virus isolation. RESULTS: Overall, 9196 female Culicoides were
      exposed to the three BTV strains through an artificial membrane, with feeding
      rates of 14-27%. Survival rates of blood-engorged Culicoides females at eight
      days post-infection depended on both virus serotype and altitude of origin. Virus
      dissemination (Cq <= the cut-off value as determined by serial virus dilutions)
      was confirmed only for BTV-1 in C. scoticus (dissemination efficiency 22.5%;
      9/40) and C. obsoletus (5.6%; 1/18) from the Swiss Plateau area. There was no
      strong evidence of susceptibility to infection for Culicoides from the pre-alpine
      area when fed with all BTV strains (BTV-1, 4 and 8). CONCLUSIONS: This study
      confirms the susceptibility of C. scoticus and C. obsoletus to BTV-1 infection,
      including under cooler temperatures. Culicoides grisescens, which is highly
      abundant at higher altitudes, cannot be considered a potential vector under these
      temperature conditions.

PMID- 30103806
TI  - Risk factors of preterm birth among mothers who gave birth in public hospitals of
      central zone, Tigray, Ethiopia: unmatched case-control study 2017/2018.
AB  - OBJECTIVE: The aim of the study was to identify the risk factors for preterm
      birth in public hospitals of the central zone, Tigray, Ethiopia 2017/2018.
      RESULT: A total of 88 neonates who born preterm (cases) and 176 neonates who born
      term (controls) with their index mothers were included making a response rate of
      100%. About 84/88 (95.5%) mothers in cases and 173/176 (98.3%) in control had
      antenatal care follow up. Among them, 33 (39.3%) cases and 102 (58%) controls
      were had antenatal care follow up four times and above. In multiple logistic
      regression at P-value < 0.05, mothers with ANC follow up less than four [AOR 95%
      CI 2.15 (1.19, 3.85)], mothers with pregnancy-induced hypertension [AOR 3.245;
      95% CI (1.58, 6.67)], multiple pregnancy [AOR 2.47; 95% CI (1.14, 5.33)], fetal
      distress [AOR 4.0; 95% CI (1.9, 8.2)] and birth defect [AOR 3.19; 95% CI (1.22,
      8.34)] were independent risk factors of preterm delivery.

PMID- 30103807
TI  - Multiple myeloma concealed by adrenal Cushing syndrome: a case report and review
      of the literature.
AB  - BACKGROUND: Cushing syndrome coexisting with multiple myeloma has been previously
      described in a few reports. Overlapping clinical manifestations can lead to
      misdiagnoses. CASE PRESENTATION: We presented an extremely rare case of a 33-year
      old Thai woman with concomitant kappa light chain myeloma with adrenal Cushing
      syndrome, both of which were related to skeletal manifestations. A precedence
      report indicated that treatment of the Cushing syndrome could exacerbate the
      myeloma symptoms. Therefore, we were faced with the dilemma of which disease
      should be addressed first. We decided to treat our patient with a combination
      chemotherapy followed by an autologous stem cell transplant. Subsequently, a left
      laparoscopic adrenalectomy was successfully undertaken. CONCLUSION: We have
      reported the first association between adrenocorticotropic hormone-independent
      Cushing syndrome resulting from a left autonomous cortisol-secreting adrenal
      adenoma, and multiple myeloma.

PMID- 30103805
TI  - Diagnostic accuracy of fine needle aspiration biopsy in pediatric small round
      cell tumors.
AB  - OBJECTIVE: Fine needle aspiration biospy (FNAB) is a simple, cost effective
      procedure, which can be carried out in the out-patient department. The objective
      of our study was to determine the diagnostic accuracy of fine needle aspiration
      biopsy in small round cell tumors of childhood, keeping histopathology as the
      gold standard. RESULTS: Out of these 50 cases, 35 (70%) were small round cell
      tumors and 15 (30%) cases of other childhood malignancies and certain reactive
      conditions. In our study, the most common malignant small round cell tumor (SRCT)
      on histopathology was Wilms tumor (10 cases) followed by non Hodgkin lymphoma (9
      cases). FNAB results were correlated with the histological findings and the
      diagnostic accuracy of SRCT came out to be 98%. The sensitivity and specificity
      of FNAB in diagnosing SRCT was 97% and 100% respectively. FNAB was found to be a
      very useful technique in the initial evaluation of any palpable lesion of
      childhood. Although the small round cell tumors appear cytologically similar, in
      the hands of experienced cytopathologists, the subtle morphological features can
      help towards the final diagnosis. In addition, clinical and radiological findings
      are invaluable assets, which help to reach the final diagnosis.

PMID- 30103804
TI  - Loss of SETDB1 decompacts the inactive X chromosome in part through reactivation
      of an enhancer in the IL1RAPL1 gene.
AB  - BACKGROUND: The product of dosage compensation in female mammals is the inactive
      X chromosome (Xi). Xi facultative heterochromatin is organized into two different
      types, one of which is defined by histone H3 trimethylated at lysine 9 (H3K9me3).
      The rationale for this study was to assess SET domain bifurcated 1 (SETDB1) as a
      candidate for maintaining this repressive modification at the human Xi. RESULTS:
      Here, we show that loss of SETDB1 does not result in large-scale H3K9me3 changes
      at the Xi, but unexpectedly we observed striking decompaction of the Xi
      territory. Close examination revealed a 0.5 Mb region of the Xi that transitioned
      from H3K9me3 heterochromatin to euchromatin within the 3' end of the IL1RAPL1
      gene that is part of a common chromosome fragile site that is frequently deleted
      or rearranged in patients afflicted with intellectual disability and other
      neurological ailments. Centrally located within this interval is a powerful
      enhancer adjacent to an ERVL-MaLR element. In the absence of SETDB1, the enhancer
      is reactivated on the Xi coupled with bidirectional transcription from the ERVL
      MaLR element. Xa deletion of the enhancer/ERVL-MaLR resulted in loss of full
      length IL1RAPL1 transcript in cis, coupled with trans decompaction of the Xi
      chromosome territory, whereas Xi deletion increased detection of full-length
      IL1RAPL1 transcript in trans, but did not impact Xi compaction. CONCLUSIONS:
      These data support a critical role for SETDB1 in maintaining the ERVL-MaLR
      element and adjacent enhancer in the 3' end of the IL1RAPL1 gene in a silent
      state to facilitate Xi compaction.

PMID- 30103808
TI  - Successful nonsurgical therapy of a diabetic foot osteomyelitis in a patient with
      peripheral artery disease with almost complete radiological restoration.
AB  - BACKGROUND: Diabetic foot ulcer (DFU) is a common complication in patients with
      diabetes mellitus (DM) and can consequently lead to soft tissue infection and
      osteomyelitis. CASE PRESENTATION: We present a case of a 68-year-old man with a
      history of Type 2 DM and symptomatic peripheral artery disease, referred to our
      hospital due to an infected lower extremity DFU. Cultures revealed methicillin
      resistant Staphylococcus aureus and Stenotrophomonas maltophilia. There was a
      significant increase of inflammatory marker levels and plain X-rays revealed
      osteomyelitis. He underwent lower extremity angioplasty for the restoration of
      the blood flow. He received targeted intravenous antibiotic therapy for 2 weeks
      and continued ciprofloxacin along with clindamycin per os for 10 more weeks as
      outpatient. CONCLUSION: As a result, the patient presented almost complete
      healing of his DFU, reconstruction of osteomyelitis defects in X-ray and complete
      restoration of his foot functionality only 4 months after the end of the
      treatment. This case demonstrates a DFU complicated by osteomyelitis which
      resolved medically and nonsurgically, with the exception of surgical restoration
      of the blood flow.

PMID- 30103809
TI  - The tick endosymbiont Candidatus Midichloria mitochondrii and selenoproteins are
      essential for the growth of Rickettsia parkeri in the Gulf Coast tick vector.
AB  - BACKGROUND: Pathogen colonization inside tick tissues is a significant aspect of
      the overall competence of a vector. Amblyomma maculatum is a competent vector of
      the spotted fever group rickettsiae, Rickettsia parkeri. When R. parkeri
      colonizes its tick host, it has the opportunity to dynamically interact with not
      just its host but with the endosymbionts living within it, and this enables it to
      modulate the tick's defenses by regulating tick gene expression. The microbiome
      in A. maculatum is dominated by two endosymbiont microbes: a Francisella-like
      endosymbiont (FLE) and Candidatus Midichloria mitochondrii (CMM). A range of
      selenium-containing proteins (selenoproteins) in A. maculatum ticks protects them
      from oxidative stress during blood feeding and pathogen infections. Here, we
      investigated rickettsial multiplication in the presence of tick endosymbionts and
      characterized the functional significance of selenoproteins during R. parkeri
      replication in the tick. RESULTS: FLE and CMM were quantified throughout the tick
      life stages by quantitative PCR in R. parkeri-infected and uninfected ticks. R.
      parkeri infection was found to decrease the FLE numbers but CMM thrived across
      the tick life cycle. Our qRT-PCR analysis indicated that the transcripts of genes
      with functions related to redox (selenogenes) were upregulated in ticks infected
      with R. parkeri. Three differentially expressed proteins, selenoprotein M,
      selenoprotein O, and selenoprotein S were silenced to examine their functional
      significance during rickettsial replication within the tick tissues. Gene
      silencing of the target genes was found to impair R. parkeri colonization in the
      tick vector. Knockdown of the selenogenes triggered a compensatory response from
      other selenogenes, as observed by changes in gene expression, but oxidative
      stress levels and endoplasmic reticulum stress inside the ticks were also found
      to have heightened. CONCLUSIONS: This study illustrates the potential of this new
      research model for augmenting our understanding of the pathogen interactions
      occurring within tick hosts and the important roles that symbionts and various
      tick factors play in regulating pathogen growth.

PMID- 30103810
TI  - Modelling local areas of exposure to Schistosoma japonicum in a limited survey
      data environment.
AB  - BACKGROUND: Spatial modelling studies of schistosomiasis (SCH) are now
      commonplace. Covariate values are commonly extracted at survey locations, where
      infection does not always take place, resulting in an unknown positional exposure
      mismatch. The present research aims to: (i) describe the nature of the positional
      exposure mismatch in modelling SCH helminth infections; (ii) delineate exposure
      areas to correct for such positional mismatch; and (iii) validate exposure areas
      using human positive cases. METHODS: To delineate exposure areas to Schistosoma
      japonicum, a spatial Bayesian network (sBN) was constructed. It uses data on
      exposure risk factors such as: potential sites for snails' accessibility,
      geographical distribution of snail infection rate, and cost of the community to
      access nearby water bodies. Prior and conditional probabilities were obtained
      from the literature and inserted as weights based on their relative contribution
      to exposure; these probabilities were then used to calculate joint probabilities
      of exposure within the sBN. RESULTS: High values of probability of S. japonicum
      exposure correspond to polygons where snails could potentially be present, for
      instance in wet soils and areas with low slopes, but also where people can easily
      access water bodies. Low correlation (R2 = 0.3) was found between the percentage
      of human cases and the delineated probabilities of exposure when validation
      buffers are generated over the human cases. CONCLUSIONS: The utility of a
      probabilistic method for the identification of exposure areas for S. japonicum,
      with wider application for other water-borne infections, was demonstrated. From a
      public health perspective, the schistosomiasis exposure sBN developed in this
      study could be used to guide local schistosomiasis control teams to specific
      potential areas of exposure, and improve efficiency of mass drug administration
      campaigns in places where people are likely to be exposed to the infection.

PMID- 30103811
TI  - Melanotic Xp11 translocation renal cancer: a report of a distinctive case and a
      review of the literature.
AB  - BACKGROUND: Melanotic Xp11 translocation renal cancer (TRC) is a newly described
      exceedingly rare tumor, and its characterization remains controversial. This
      study aimed to describe a case of distinctive melanotic Xp11 TRC and to elucidate
      its clinicopathological and molecular genetic features. CASE PRESENTATION: A 44
      year-old Chinese female presented with a left renal mass. Abdominal
      ultrasonography and computed tomography (CT) scans revealed a 4.5 cm * 4.0 cm
      mass in the left kidney. Grossly, the well-demarcated mass was black with
      moderately firm consistency. Microscopic examination indicated that the tumor was
      characterized by the presence of nests and cords of polygonal cells with clear
      and granular eosinophilic cytoplasm, central round to oval nuclei and occasional
      nucleoli. Intracytoplasmic melanin was observed in approximately 45% of tumor
      cells. Uniquely, the tumor presented with intranuclear eosinophilic
      pseudoinclusions and thick-walled stromal blood vessels. IHC showed that tumor
      cells were diffusely positive for TFE3 and exhibited patchy and weak HMB45
      staining. FISH confirmed the presence of TFE3 rearrangement. CONCLUSION: This
      case is the twentieth published case of melanotic Xp11 TRC. Moreover, the present
      patient had a favorable prognosis given that she was disease free at her 113
      month postoperative follow-up. Our case adds to the small body of literature on
      these exceptionally rare tumors and widens their clinicopathological spectrum.

PMID- 30103812
TI  - A pilot study on the importance of forefoot bone length in male 400-m sprinters:
      is there a key morphological factor for superior long sprint performance?
AB  - OBJECTIVE: The main purpose of the present study was to determine the
      relationship between the forefoot bone length and long sprint performance in well
      trained 400-m specialized sprinters. The total lengths of the forefoot bones of
      the big and second toes in 25 male 400-m sprinters and 25 male non-sprinters were
      measured using magnetic resonance imaging. The forefoot bones of each toe were
      totaled to assess overall forefoot bone length and then normalized to the maximum
      foot length. RESULTS: The relative total lengths of the forefoot bones in the big
      and second toes were significantly longer in 400-m sprinters than in non
      sprinters (P < 0.05 for both). The relative total length of the forefoot bones of
      the second toe, but not of the big toe, in 400-m sprinters was significantly
      correlated with personal best 400-m sprint time (r = - 0.441, P = 0.028). These
      findings demonstrated that longer forefoot bones are related to higher long
      sprint performance in well-trained 400-m specialized sprinters. Therefore, the
      present study is the first to determine that morphological factors such as long
      forefoot bones may play an important role in achieving superior long sprinting
      performance.

PMID- 30103813
TI  - Utilization of insecticide treated bed net and associated factors among
      households of Kola Diba town, North Gondar, Amhara region, Ethiopia.
AB  - OBJECTIVE: The primary aim of this study was to assess the utilization of an
      insecticide-treated bed net on the preceding night and associated factors among
      households of Kola Diba town in 2017. RESULTS: Of the 260 households, 239 (91.9%)
      (95% CI = 88.5-95%) utilized insecticide-treated bed net on the night preceding
      the interview. 242 (93.1%) households didn't treat the bed net whereas 18 (6.9%)
      treat the bed net by chemical regularly. Household structure and knowledge about
      malaria transmission were found to be associated with insecticide-treated bed net
      utilization.

PMID- 30103814
TI  - Unilateral pulmonary edema: a case report and review of the literature.
AB  - BACKGROUND: Unilateral pulmonary edema is an uncommon condition and is a rare
      clinical entity that is often misdiagnosed at the initial stages. In a majority
      of patients it occurs in the upper lobe of the right lung. There are many causes
      of unilateral pulmonary edema, but the commonest is the presence of a grade 3
      mitral regurgitation. Due to its rare presentation, a high index of suspicion is
      required, and correct management is necessary to reduce the morbidity and
      mortality. CASE PRESENTATION: We present a case of right-sided unilateral
      pulmonary edema in an 86-year-old Sinhalese Sri Lankan woman who presented with
      acute onset dyspnea with cardiogenic shock due to acute non-ST elevation
      myocardial infarction, complicated with grade 3 mitral regurgitation. She had
      clinical features of heart failure and pulmonary edema, but a chest X-ray showed
      unilateral infiltrates only on the right side. Distinguishing pneumonia from
      pulmonary edema according to chest X-ray findings was a challenge initially, and
      she was therefore initially treated for both conditions. She had remarkable
      clinical and radiological improvement after 12 hours of intravenously
      administered furosemide and glyceryl trinitrate therapy. Her brain natriuretic
      peptide level was elevated and further supported and confirmed the diagnosis
      retrospectively. CONCLUSIONS: Unilateral pulmonary edema is a completely
      reversible condition with good patient outcome if it is suspected early and
      treated early. Even in the absence of readily available echocardiogram skills, a
      clinical examination is of paramount importance in making a clinical decision in
      low-resource settings to reduce mortality.

PMID- 30103816
TI  - EMBLmyGFF3: a converter facilitating genome annotation submission to European
      Nucleotide Archive.
AB  - OBJECTIVE: The state-of-the-art genome annotation tools output GFF3 format files,
      while this format is not accepted as submission format by the International
      Nucleotide Sequence Database Collaboration (INSDC) databases. Converting the GFF3
      format to a format accepted by one of the three INSDC databases is a key step in
      the achievement of genome annotation projects. However, the flexibility existing
      in the GFF3 format makes this conversion task difficult to perform. Until now, no
      converter is able to handle any GFF3 flavour regardless of source. RESULTS: Here
      we present EMBLmyGFF3, a robust universal converter from GFF3 format to EMBL
      format compatible with genome annotation submission to the European Nucleotide
      Archive. The tool uses json parameter files, which can be easily tuned by the
      user, allowing the mapping of corresponding vocabulary between the GFF3 format
      and the EMBL format. We demonstrate the conversion of GFF3 annotation files from
      four different commonly used annotation tools: Maker, Prokka, Augustus and
      Eugene. EMBLmyGFF3 is freely available at https://github.com/NBISweden/EMBLmyGFF3
      .

PMID- 30103815
TI  - Prenatal influenza vaccination rescues impairments of social behavior and
      lamination in a mouse model of autism.
AB  - BACKGROUND: Prenatal infection is a substantial risk factor for
      neurodevelopmental disorders such as autism in offspring. We have previously
      reported that influenza vaccination (VAC) during early pregnancy contributes to
      neurogenesis and behavioral function in offspring. RESULTS: Here, we probe the
      efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide
      (LPS)-induced maternal immune activation (MIA) mouse model. We show that VAC
      improves abnormal fetal brain cytoarchitecture and lamination, an effect
      associated with promotion of intermediate progenitor cell differentiation in MIA
      fetal brain. These beneficial effects are sufficient to prevent social deficits
      in adult MIA offspring. Furthermore, whole-genome analysis suggests a strong
      interaction between Ikzf1 (IKAROS family zinc-finger 1) and neuronal
      differentiation. Intriguingly, VAC rescues excessive microglial Ikzf1 expression
      and attenuates microglial inflammatory responses in the MIA fetal brain.
      CONCLUSIONS: Our study implies that a preprocessed influenza vaccination prevents
      maternal bacterial infection from causing neocortical lamination impairments and
      autism-related behaviors in offspring.

PMID- 30103818
TI  - Knowledge, attitude and practice towards family planning among reproductive age
      women in a resource limited settings of Northwest Ethiopia.
AB  - OBJECTIVE: To assess the knowledge and attitude regarding family planning and the
      practice of family planning among the women of reproductive age group in South
      Achefer District, Northwest Ethiopia, 2017. RESULT: The study showed that the
      overall proper knowledge, attitude and practice of women towards family planning
      (FP) was 42.3%, 58.8%, and 50.4% respectively. Factors associated with the
      practice of FP were: residence, marital status, educational status, age,
      occupation, and knowledge, and attitude, number of children and monthly average
      household income of participants. In this study, the level of knowledge and
      attitude towards family planning was relatively low and the level of family
      planning utilization was quite low in comparison with many studies. Every health
      worker should teach the community on family planning holistically to increase the
      awareness so that family planning utilization will be enhanced. Besides, more
      studies are needed in a thorough investigation of the different reasons affecting
      the non-utilizing of family planning and how these can be addressed are
      necessary.

PMID- 30103817
TI  - Injury-induced fetal reprogramming imparts multipotency and reparative properties
      to pericardial adipose stem cells.
AB  - BACKGROUND: Injury may induce a sequential activation of intrinsic reparative
      activity that supports the maintenance of tissue homeostasis. METHOD: In the
      present experiments, we investigated whether myocardial infarction (MI) was able
      to reinstate the expression of Wilms' tumor factor 1 (WT1) as a key hallmark of
      fetal reprograming in the pericardial adipose-derived stem cells (pADSC). We
      characterized the immunophenotypical markers, cardiac potential, and reparative
      activity of WT1-expressing pADSC (WT1pos) isolated MI Wistar rats with an intact
      pericardial sac in which cardiac transudate was accumulated, sampled, and
      analyzed. RESULTS: The WT1pos cells formed colony-like aggregates in culture that
      subsequently generated phase-bright cells that homogenously constituted WT1
      expression (> 98%). The WT1pos cells shared identical surface markers with
      canonical pADSC, but enhanced transcripts for cardiogenesis (isl-1, gata-4, Sox2
      and Tbx18) as well as cardiac commitment (endothelial: 28%; cardiomyogenic:
      12.3%) in defined conditions. Remarkably, cardiac transplantation of WT1pos cells
      promoted regional angiogenesis and myogenesis which led to significant functional
      amelioration of the infarcted hearts. Furthermore, we demonstrated that WT1pos
      cells uniquely secreted hepatocyte growth factor (HGF) as a key antiapoptotic
      factor that promotes cardiac repair. CONCLUSION: Injury-associated fetal
      reprogramming in pADSC facilitates cardiac differentiation and promotes the
      reparative activity by enhancing HGF production. As such, injury-"conditioned"
      pADSC may represent a useful autologous cell donor from infarcted patients for
      cell-based therapy.

PMID- 30103819
TI  - Resilience of the resident soil microbiome to organic and inorganic amendment
      disturbances and to temporary bacterial invasion.
AB  - BACKGROUND: Vinasse, a by-product of sugarcane ethanol production, is recycled by
      sugarcane plantations as a fertilizer due to its rich nutrient content. However,
      the impacts of the chemical and microbial composition of vinasse on soil
      microbiome dynamics are unknown. Here, we evaluate the recovery of the native
      soil microbiome after multiple disturbances caused by the application of organic
      vinasse residue, inorganic nitrogen, or a combination of both during the
      sugarcane crop-growing season (389 days). Additionally, we evaluated the
      resistance of the resident soil microbial community to the vinasse microbiome.
      RESULTS: Vinasse applied alone or 30 days prior to N resulted in similar changes
      in the soil microbial community. Furthermore, the impact of the application of
      vinasse together with N fertilizer on the soil microbial community differed from
      that of N fertilizer alone. Organic vinasse is a source of microbes, nutrients,
      and organic matter, and the combination of these factors drove the changes in the
      resident soil microbial community. However, these changes were restricted to a
      short period of time due to the capacity of the soil community to recover. The
      invasive bacteria present in the vinasse microbiome were unable to survive in the
      soil conditions and disappeared after 31 days, with the exception of the
      Acetobacteraceae (native in the soil) and Lactobacillaceae families. CONCLUSION:
      Our analysis showed that the resident soil microbial community was not resistant
      to vinasse and inorganic N application but was highly resilient.

PMID- 30103820
TI  - Utility of the Dependence Scale in dementia: validity, meaningfulness, and health
      economic considerations.
AB  - BACKGROUND: The concept of dependence has been proposed as a unified
      representation of disease severity to quantify and stage disease progression in a
      manner more informative to patients, caregivers, and healthcare providers.
      METHODS: This paper provides a review of the Dependence Scale (DS) as a
      quantitative measure of Alzheimer's disease severity, its properties as an
      outcome measure, a metric of disease progression, and a correlate of medical
      costs. RESULTS: The literature supports the notion that the DS is related to, but
      distinct from, key severity measures, including cognition, function, and
      behavior, and captures the full spectrum of patient needs. It also presents as a
      useful measure for assessing disease progression. CONCLUSIONS: Results underscore
      the importance of the DS as a unique endpoint in Alzheimer's disease clinical
      trials, providing important information about the impact of therapeutic
      interventions. The DS also is a useful measure for economic evaluation of novel
      interventions aimed at delaying progression.

PMID- 30103821
TI  - FOXP3 knockdown inhibits the proliferation and reduces NOTCH1 expression of T
      cell acute lymphoblastic leukemia cells.
AB  - OBJECTIVE: Forkhead box P3 (FOXP3) is a master transcriptional factor of
      regulatory T-cells (Tregs). Recent studies have shown that FOXP3 is associated
      with growth inhibition of cancer cells. However, the role of FOXP3 in acute T
      lymphoblastic leukemia (T-ALL) cells is not known. It was also reported that
      NOTCH signaling promoted the expression of FOXP3 in Tregs. However, the effect of
      FOXP3 on NOTCH expression in T-ALL cells is little known. Therefore, we examined
      the effect of FOXP3 knockdown on the proliferation of T-ALL cells and NOTCH1
      signaling. RESULTS: Two T-ALL cell lines Jurkat and KOPT-K1, harboring activating
      NOTCH1 mutations, were transfected with small interfering RNA against FOXP3. Cell
      growth was assessed with a colorimetric assay and morphology was observed under a
      microscope. FOXP3 knockdown significantly reduced cell growth and induced
      morphological changes suggesting apoptosis. Quantitative polymerase chain
      reaction revealed that FOXP3 knockdown caused the downregulation of mRNA
      expression of NOTCH1 and HES1. These findings suggest that FOXP3 supports the
      growth of T-ALL cells although this can not be generalized because we examined
      only two cell lines. The observed growth suppression can be partly due to the
      downregulation of NOTCH1 signaling. FOXP3 may be a potential therapeutic target
      in T-ALL.

PMID- 30103822
TI  - Extensive abdominal wall ulceration as a late manifestation of antiphospholipid
      syndrome: a case report.
AB  - BACKGROUND: Antiphospholipid syndrome is an autoimmune disorder characterized by
      the presence of antiphospholipid antibodies and commonly presents with vascular
      thromboembolic phenomena, thrombocytopenia, and obstetric complications.
      Antiphospholipid syndrome can be classified as either primary or secondary to
      other connective tissue diseases. Dermatologic manifestations are common;
      however, non-vasculitic skin ulceration is an uncommon manifestation of
      antiphospholipid syndrome with limited treatment options. CASE PRESENTATION: In
      this paper we report the case of a 58-year-old white woman who developed necrotic
      abdominal wall ulcers 27 years after a diagnosis of secondary antiphospholipid
      syndrome associated with systemic lupus erythematosus. The ulcers developed
      despite our patient being on therapeutic anticoagulation with warfarin and were
      resistant to further increases in the intensity of anticoagulation. Management
      was further complicated due to reluctance on the part of our patient to switch
      over to injectable heparin. CONCLUSIONS: This case highlights a rare late
      dermatologic presentation of antiphospholipid syndrome, which responded poorly to
      conventional anticoagulation with warfarin. Current management is limited to
      experimental therapies and the role of newer anticoagulants is still unknown.

PMID- 30103824
TI  - Role of antenatal and postnatal care in contraceptive use during postpartum
      period in western Ethiopia: a cross sectional study.
AB  - OBJECTIVE: Little has been known about the magnitude and predictors of
      contraceptive use in extended postpartum period in Ethiopia. Thus, this study
      aims to assess the magnitude and determinants of contraception utilization in
      extended postpartum period. A community based cross-sectional survey was
      conducted in Gida Ayana district, Oromia regional state, Ethiopia in February
      2015. Six hundred and three postpartum women were included using a multistage
      sampling technique. Descriptive statistics were used to summarize the data and
      logistic regressions were used to assess the predictors of modern family planning
      use at 95% confidence interval. RESULTS: The proportion of women using any of the
      modern family planning in extended postpartum period was 45.4%. Women who had
      four and more antenatal care visits (AOR = 2.93; 95% CI 1.08-7.94), mothers who
      received post-natal care (AOR = 4.34; 95% CI 2.37-7.94), and those desiring less
      number of children (AOR = 5; 95% CI 2.19-11.41) were more likely to use modern
      family planning methods during the extended postpartum period. Therefore, health
      care providers should work to improve quality of health services provided during
      antenatal care and postnatal care to enhance family planning utilization among
      post-partum women.

PMID- 30103823
TI  - Mosquitoes (Diptera: Culicidae) and mosquito-borne diseases in Mali, West Africa.
AB  - Mosquito-borne diseases cause major human diseases in almost every part of the
      world. In West Africa, and notably in Mali, vector control measures help reduce
      the impact of mosquito-borne diseases, although malaria remains a threat to both
      morbidity and mortality. The most recent overview article on mosquitoes in Mali
      was published in 1961, with a total of 88 species. Our present review focuses on
      mosquitoes of medical importance among which the Anopheles vectors of Plasmodium
      and filaria, as well as the Culex and Aedes vectors of arboviruses. It aims to
      provide a concise update of the literature on Culicidae, covering the ecological
      areas in which the species are found but also the transmitted pathogens and
      recent innovative tools for vector surveys. This review highlights the recent
      introduction of invasive mosquito species, including Aedes albopictus and Culex
      neavei. The comprehensive list of mosquito species currently recorded includes
      106 species (28 species of the Anophelinae and 78 species of the Culicinae).
      There are probable gaps in our knowledge concerning mosquitoes of the subfamily
      Culicinae and northern half of Mali because most studies have been carried out on
      the genus Anopheles and have taken place in the southern part of the country. It
      is hoped that this review may be useful to decision makers responsible for vector
      control strategies and to researchers for future surveys on mosquitoes,
      particularly the vectors of emerging arboviruses.

PMID- 30103825
TI  - Changes in malaria vector bionomics and transmission patterns in the equatorial
      forest region of Cameroon between 2000 and 2017.
AB  - BACKGROUND: Increased use of long-lasting insecticidal nets (LLINs) over the last
      decade has considerably improved the control of malaria in sub-Saharan Africa.
      However, there is still a paucity of data on the influence of LLIN use and other
      factors on mosquito bionomics in different epidemiological foci. The objective of
      this study was to provide updated data on the evolution of vector bionomics and
      malaria transmission patterns in the equatorial forest region of Cameroon over
      the period 2000-2017, during which LLIN coverage has increased substantially.
      METHODS: The study was conducted in Olama and Nyabessan, two villages situated in
      the equatorial forest region. Mosquito collections from 2016-2017 were compared
      to those of 2000-2001. Mosquitoes were sampled using both human landing catches
      and indoor sprays, and were identified using morphological taxonomic keys.
      Specimens belonging to the An. gambiae complex were further identified using
      molecular tools. Insecticide resistance bioassays were undertaken on An. gambiae
      to assess the susceptibility levels to both permethrin and deltamethrin.
      Mosquitoes were screened for Plasmodium falciparum infection and blood-feeding
      preference using the ELISA technique. Parasitological surveys in the population
      were conducted to determine the prevalence of Plasmodium infection using rapid
      diagnostic tests. RESULTS: A change in the species composition of sampled
      mosquitoes was recorded between the 2000-2001 collections and those of 2016-2017.
      A drop in the density of the local primary vectors An. nili and An. moucheti in
      the forest region was recorded, whereas there was an increase in the density of
      An. gambiae (s.l.), An. marshallii, An. ziemannii and An. paludis. A change in
      the biting behaviour from indoor to outdoor was recorded in Olama. Very few
      indoor resting mosquitoes were collected. A change in the night biting cycle was
      recorded with mosquitoes displaying a shift from night biting to late
      evening/early in the night. Several mosquitoes were found positive for Plasmodium
      infection, thus sustaining continuous transmission of malaria in both sites.
      Reduction of malaria transmission in Nyabessan was lower than that seen in Olama
      and associated with deforestation and the construction of a dam that may have
      enabled a more efficient vector, An. gambiae (s.l.), to invade the area. A high
      level of resistance to pyrethroids (permethrin and deltamethrin) was detected for
      An. gambiae in both sites. High parasite prevalence was recorded in both sites,
      with children of 0-16 years being the most affected. In both Olama and Nyabessan,
      bed net usage appeared to correlate to protection against malaria infection.
      CONCLUSIONS: The study shows important changes in the bionomics of vector
      populations and malaria transmission patterns in the equatorial forest region.
      The changes call for more concerted efforts to address challenges such as
      insecticide resistance, environmental modifications or behavioural changes
      affecting the performance of current control measures.

PMID- 30103826
TI  - Genomic exploration of sequential clinical isolates reveals a distinctive
      molecular signature of persistent Staphylococcus aureus bacteraemia.
AB  - BACKGROUND: Large-scale genomic studies of within-host diversity in
      Staphylococcus aureus bacteraemia (SAB) are needed to understanding bacterial
      adaptation underlying persistence and thus refining the role of genomics in
      management of SAB. However, available comparative genomic studies of sequential
      SAB isolates have tended to focus on selected cases of unusually prolonged
      bacteraemia, where secondary antimicrobial resistance has developed. METHODS: To
      understand bacterial genetic diversity during SAB more broadly, we applied whole
      genome sequencing to a large collection of sequential isolates obtained from
      patients with persistent or relapsing bacteraemia. After excluding genetically
      unrelated isolates, we performed an in-depth genomic analysis of point mutations
      and chromosome structural variants arising within individual SAB episodes.
      RESULTS: We show that, while adaptation pathways are heterogenous and episode
      specific, isolates from persistent bacteraemia have a distinctive molecular
      signature, characterised by a low mutation frequency and high proportion of non
      silent mutations. Analysis of structural genomic variants revealed that these
      often overlooked genetic events are commonly acquired during SAB. We discovered
      that IS256 insertion may represent the most effective driver of within-host
      microevolution in selected lineages, with up to three new insertion events per
      isolate even in the absence of other mutations. Genetic mechanisms resulting in
      significant phenotypic changes, such as increases in vancomycin resistance,
      development of small colony phenotypes, and decreases in cytotoxicity, included
      mutations in key genes (rpoB, stp, agrA) and an IS256 insertion upstream of the
      walKR operon. CONCLUSIONS: This study provides for the first time a large-scale
      analysis of within-host genomic changes during invasive S. aureus infection and
      describes specific patterns of adaptation that will be informative for both
      understanding S. aureus pathoadaptation and utilising genomics for management of
      complicated S. aureus infections.

PMID- 30103827
TI  - Overexpression of amplified in breast cancer 1 (AIB1) gene promotes lung
      adenocarcinoma aggressiveness in vitro and in vivo by upregulating C-X-C motif
      chemokine receptor 4.
AB  - BACKGROUND: We previously found that overexpression of the gene known as
      amplified in breast cancer 1 (AIB1) was associated with lymph node metastasis and
      poor prognosis in patients with lung adenocarcinoma. However, the role of AIB1 in
      that malignancy remains unknown. The present study aimed to investigate the
      function of AIB1 in the process of lung adenocarcinoma cell metastasis. METHODS:
      A series of in vivo and in vitro assays were performed to elucidate the function
      of AIB1, while real-time PCR and Western blotting were utilized to identify the
      potential downstream targets of AIB1 in the process of lung adenocarcinoma
      metastasis. Rescue experiments and in vitro assays were performed to investigate
      whether the invasiveness of AIB1-induced lung adenocarcinoma was mediated by C-X
      C motif chemokine receptor 4 (CXCR4). RESULTS: The ectopic overexpression of AIB1
      in lung adenocarcinoma cells substantially enhanced cell migration and invasive
      abilities in vitro and tumor metastasis in vivo, whereas the depletion of AIB1
      expression substantially inhibited lung adenocarcinoma cell migration and
      invasion. CXCR4 was identified as a potential downstream target of AIB1 in lung
      adenocarcinoma. The knockdown of AIB1 greatly reduced CXCR4 gene expression at
      both the transcription and protein levels, whereas the knockdown of CXCR4 in
      cells with AIB1 ectopic overexpression diminished AIB1-induced migration and
      invasion in vitro and tumor metastasis in vivo. Furthermore, we found a
      significant positive association between the expression of AIB1 and CXCR4 in lung
      adenocarcinoma patients (183 cases), and the co-overexpression of AIB1 and CXCR4
      predicted the poorest prognosis. CONCLUSIONS: These findings suggest that AIB1
      promotes the aggressiveness of lung adenocarcinoma in vitro and in vivo by
      upregulating CXCR4 and that it might be usable as a novel prognostic marker
      and/or therapeutic target for this disease.

PMID- 30103829
TI  - BRCA1 and BRCA2 mutations and clinical interpretation in 398 ovarian cancer
      patients: comparison with breast cancer variants in a similar population.
AB  - BACKGROUND: Ovarian cancer is the leading cause of death worldwide among
      gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose)
      polymerase (iPARP) in the treatment of ovarian cancer in the presence of a
      BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can
      further benefit from the detection of carriers in the family. Germline sequence
      and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial
      ovarian cancer (EOC) patients. The aim of this study was to identify the
      frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of
      patients with ovarian serous carcinoma, with a view to adequately selecting
      patients for prevention through family counseling and correlating this frequency
      with platinum sensitivity as a guidance to identify patients eligible for iPARP
      in our population. RESULTS: A total of 96 patients carried a pathogenic germline
      mutation, accounting for an overall 24.1% mutation incidence. Among mutation
      carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient
      exhibited a mutation in both genes. Three pathogenic mutations were recurrent
      mutations detected five, three, and four times and represented 12.5% of the
      mutated samples. Worth highlighting, a 50% mutation incidence was detected when
      breast and ovarian cancer coexisted in the same patient. Novel mutations amounted
      to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out
      of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in
      stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken
      together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational
      spectrum compared to our previously published data on breast cancer patients.
      CONCLUSIONS: In sum, our study provides novel data on ovarian BRCA1/2 mutation
      prevalence worldwide, enhances adequate patient selection for family counseling
      and prevention, and sheds light on the benefits of iPARP treatment.

PMID- 30103830
TI  - An exploratory pilot study on health education program to improve health literacy
      among female in their 20s.
AB  - OBJECTIVE: Health literacy (HL) is one of the most important concepts in women's
      healthcare. The low cervical cancer screening rate for young Japanese women is an
      urgent issue. Cervical cancer is preventable, and cervical cancer screening
      behavior is associated with HL. Therefore, the present study aimed to elucidate
      the effects of a health education program to improve HL among young female
      undergraduate students in Japan. Immediately after completing the program,
      participants evaluated their level of satisfaction with and the level of
      difficulty of the program, their understanding of the educational materials, and
      the length of the curriculum. Furthermore, 1 month after completing the program,
      participants evaluated their overall HL and their knowledge of women's health,
      and indicated whether they had undergone cervical cancer screening. RESULTS:
      Thirteen female undergraduate students in their 20s participated. All
      participants indicated high levels of satisfaction and understanding of the
      material, and an appropriate level of difficulty of the curriculum. Three
      participants indicated that the program was too long. All participants had
      improved HL and knowledge of women's health after completing the education
      program, but no significant difference was observed in the cervical cancer
      screening rate. Trial registration UMINR000036690 April 10, 2018 retrospectively
      registered.

PMID- 30103828
TI  - An update of the Culicoides (Diptera: Ceratopogonidae) checklist for the Balkans.
AB  - BACKGROUND: The prime significance of species belonging to the genus Culicoides
      Latreille, 1809 (Diptera: Ceratopogonidae) is their ability to transmit viruses
      such as bluetongue virus (BTV) to wild and domestic ruminants. Prior to 1998, BTV
      was considered exotic in Europe, but according to recent history of its
      outbreaks, it has become endemic in southern and eastern European countries
      circulating beyond its expected historical limits, into the Balkan region. The
      wind-borne long-distance dispersal of Culicoides spp. over water bodies and local
      spreading between farms emphasize the necessity of filling in the information
      gaps regarding vector species distribution. In most Balkan countries, data on
      Culicoides fauna and species distribution are lacking, or information is old and
      scarce. RESULTS: During this study, 8586 specimens belonging to 41 species were
      collected. We present the first faunistic data on Culicoides species in the
      former Yugoslav Republic of Macedonia (FYROM), Kosovo, Montenegro and Serbia. For
      other countries (Bosnia and Herzegovina, Bulgaria and Croatia), all historical
      records were compiled for the first time and then expanded with our findings to
      various extents. In all countries, confirmed or suspected BTV vector species
      belonging to the subgenera Avaritia and Culicoides were collected. The total
      number of species sampled during our field collections was 20 in Bosnia and
      Herzegovina (15 new records), 10 in Bulgaria (2 new records), 10 in Croatia (5
      new records), 13 in FYROM, 9 in Kosovo, 15 in Montenegro, and 28 in Serbia. Of
      these, 14 species were registered for the first time in this part of the Balkans.
      CONCLUSIONS: This paper provides the first data about Culicoides fauna in FYROM,
      Kosovo, Montenegro and Serbia, as well as new records and an update on the
      checklists for Bosnia and Herzegovina, Bulgaria and Croatia. These findings
      provide preliminary insights into the routes of BTV introduction and spreading
      within the Balkans, and present a valuable contribution to further research
      related to Culicoides-borne diseases in Europe.

PMID- 30103831
TI  - Rifampicin resistance in new bacteriologically confirmed pulmonary tuberculosis
      patients in Cameroon: a cross-sectional survey.
AB  - OBJECTIVE: In Cameroon, tuberculosis (TB) cases are diagnosed and treated within
      a nationwide network of 248 diagnostic and treatment centres. In 2016, the
      centers notified a total of 175 multidrug-resistant (MDR-)TB cases, most of them
      retreatment cases. According to the WHO, the expected number of MDR-TB cases was
      estimated to be 1200 (1000-2200) corresponding to a rate of 6.8 (4.3-9.4) per
      100,000 population. This indicates a notification gap of more than 80%. The
      objective of this study was to estimate the prevalence of MDR-TB in new
      bacteriologically confirmed pulmonary TB cases. We undertook a nationwide cross
      sectional survey during 6 weeks. RESULTS: During the study period, the NTP
      notified 1478 new bacteriologically confirmed pulmonary TB cases. Among them,
      1029 (70%) had a valid Xpert result and 16 were identified with rifampicin
      resistant (RR-TB), a tracer of MDR-TB. This gives a prevalence of 1.6% (95% CI
      0.8-2.3) among incident cases. The rate of RR-TB in the regions varied between 0
      and 3.3%. If the results of this study are confirmed, the incidence rate given by
      WHO (2.8%, 95% CI 2.1-3.4) might be an over-estimation.

PMID- 30103834
TI  - The Deaf community and Irish sign language.

PMID- 30103833
TI  - The epidemiological impact and significance of carbapenem resistance in
      Pseudomonas aeruginosa bloodstream infections: a matched case-case-control
      analysis.
AB  - A case-case-control investigation (N = 255 patients) explored the epidemiology of
      carbapenem-resistant Pseudomonas aeruginosa (CRPA). Recent exposure to
      carbapenems and a rapidly fatal condition should prompt practitioners to shorten
      delays in initiating appropriate therapy, which can adversely impact CRPA
      outcomes, as opposed to the isolated impact of the carbapenem resistance
      determinant.

PMID- 30103832
TI  - The impact of genome-wide association studies on biomedical research
      publications.
AB  - The past decade has seen major investment in genome-wide association studies
      (GWAS). Among the many goals of GWAS, a major one is to identify and motivate
      research on novel genes involved in complex human disease. To assess whether this
      goal is being met, we quantified the effect of GWAS on the overall distribution
      of biomedical research publications and on the subsequent publication history of
      genes newly associated with complex disease. We found that the historical skew of
      publications toward genes involved in Mendelian disease has not changed since the
      advent of GWAS. Genes newly implicated by GWAS in complex disease do experience
      additional publications compared to control genes, and they are more likely to
      become exceptionally studied. But the magnitude of both effects has declined over
      the past decade. Our results suggest that reforms to encourage follow-up studies
      may be needed for GWAS to most successfully guide biomedical research toward the
      molecular mechanisms underlying complex human disease.

PMID- 30103835
TI  - Is vaccinating monkeys against yellow fever the ultimate solution for the
      Brazilian recurrent epizootics?
AB  - Vaccinating monkeys against yellow fever (YF) has been a common practice in the
      beginning of the 17D vaccine development. Although it may seem strange at first
      sight, vaccinating monkeys as a public health strategy is, we think, feasible and
      theoretically could eliminate the infection among non-human primates,
      interrupting the virus circulation (or significantly reducing it) and therefore
      reducing the risk of spilling over to the human population. We propose a series
      of studies that could demonstrate (or not) the efficacy and feasibility of
      vaccinating non-human primates YF reservoirs living in green areas of urban
      centres to cut off or curb the virus circulation that recurrently spill over to
      the human population. Therefore, vaccinating monkeys in relatively small green
      areas of the urban centres is perhaps the ultimate solution for the Brazilian
      recurrent YF epizootics.

PMID- 30103836
TI  - General thoughts of death and mortality: findings from the Komo-Ise cohort,
      Japan.
AB  - : AimsDeath ideation (thinking about/wishing for one's own death, thinking that
      one would be better off dead) is linked to an increased mortality risk. However,
      comparatively little is known about more general thoughts of death (GTOD) where
      no wish to die or life value is expressed. This study examined whether GTOD
      predicted mortality in a community-based cohort of older adults. METHODS: Data
      came from the Komo-Ise cohort study in Gunma prefecture, Japan. The analytic
      sample comprised 8208 individuals (average age 61.3 (range 47-77)) who were asked
      in wave 2 of the study in 2000 if they had 'Thought about death more than usual,
      either your own, someone else's or death in general?' in the past 2 weeks. Death
      data were obtained from the municipal resident registration file. Cox
      proportional hazards regression analysis was used to examine associations.
      RESULTS: During the follow-up period (2000-2008), there were 672 deaths. In a
      model adjusted for baseline covariates, GTOD were significantly associated with
      all-cause mortality (hazards ratio 1.66, 95% confidence interval 1.20-2.29).
      Stratified analyses showed an association between GTOD and mortality in men,
      older subjects (?70 years), married individuals and those with higher social
      support. CONCLUSIONS: GTOD are associated with an increased mortality risk among
      older citizens in Japan. Research is now needed to determine the factors
      underlying this association and assess the clinical relevance of screening for
      GTOD in older individuals.

PMID- 30103837
TI  - Maternal preconception weight trajectories, pregnancy complications and
      offspring's childhood physical and cognitive development.
AB  - There is limited evidence on the association between maternal preconception body
      mass index (BMI) trajectories and pregnancy complications and child development.
      This study examined the relationships of maternal BMI trajectories, diabetes and
      hypertensive disorders during pregnancy and offspring's childhood physical and
      cognitive development. Data were from the Australian Longitudinal Study on
      Women's Health and the Mothers and their Children's Health study (n=771). Women's
      preconception BMI trajectories were identified using group-based trajectory
      modelling. Children's physical and cognitive development (up to the average age
      of 5 years) were obtained from the Ages and Stages Questionnaire (suspected gross
      motor delay) and the Australian Early Development Census (AEDC). Generalized
      estimating equation models, adjusted for maternal sociodemographic and lifestyle
      factors, were used for analyses. Three distinct BMI trajectories were identified
      (normative, chronically overweight and chronically obese). Children born to
      chronically obese women were more likely to be classified as developmentally
      vulnerable/at-risk on AEDC domains; gross and fine motor skills [risk ratio
      (RR)=1.64, 95% confidence interval (CI): 1.04, 2.61] and communication skills and
      general knowledge (RR=1.71, 95% CI: 1.09, 2.68). They also had an elevated risk
      of suspected gross motor delay (RR=2.62, 95% CI: 1.26, 5.44) compared with
      children born to women with a normative BMI trajectory. Maternal diabetes or
      hypertensive disorders during pregnancy were not associated with child outcomes.
      Maternal preconception BMI trajectories were associated with poorer childhood
      development. This study finding underscores the importance of excessive weight
      gain prevention throughout the reproductive stage of life.

PMID- 30103838
TI  - Salmonella source attribution in a subtropical state of Australia: capturing
      environmental reservoirs of infection.
AB  - Salmonellosis is a leading cause of hospitalisation due to gastroenteritis in
      Australia. A previous source attribution analysis for a temperate state in
      Australia attributed most infections to chicken meat or eggs. Queensland is in
      northern Australia and includes subtropical and tropical climate zones. We
      analysed Queensland notifications for salmonellosis and conducted source
      attribution to compare reservoir sources with those in southern Australia. In
      contrast to temperate Australia, most infections were due to non-Typhimurium
      serotypes, with particularly high incidence in children under 5 years and strong
      seasonality, peaking in summer. We attributed 65.3% (95% credible interval (CrI)
      60.6-73.2) of cases to either chicken meat or eggs and 15.5% (95% CrI 7.0-19.5)
      to nuts. The subtypes with the strongest associations with nuts were Salmonella
      Aberdeen, S. Birkenhead, S. Hvittingfoss, S. Potsdam and S. Waycross. All five
      subtypes had high rates of illness in children under 5 years (ranging from 4/100
      000 to 23/100 000), suggesting that nuts may be serving as a proxy for
      environmental transmission in the model. Australia's climatic range allows us to
      conduct source attribution in different climate zones with similar food
      consumption patterns. This attribution provides evidence for environment-mediated
      transmission of salmonellosis in sub-tropical regions.

PMID- 30103839
TI  - Time trends in suicide rates by domestic gas or car exhaust gas inhalation in
      Japan, 1968-1994.
AB  - : AimsA reduction in the carbon monoxide content of domestic gas and car exhaust
      gas has been associated with a decrease in gassing suicides in many western
      countries. In Japan, a reduction in the carbon monoxide content of domestic gas
      supply began in the early 1970s, and carbon monoxide emissions standards of new
      passenger cars were significantly strengthened in 1978. However, little is known
      about the impact of detoxification of these gases on gassing-related suicides in
      Japan. Therefore, we examined the changing patterns of suicide due to domestic
      gas or car exhaust gas inhalation by gender and age in Japan between 1968 and
      1994. METHODS: Suicide mortality data were obtained from the Vital Statistics of
      Japan. In this study, age was divided into four groups: 15-24, 25-44, 45-64 and
      65+ years. Method of suicide was divided into three groups: domestic gas, car
      exhaust gas and non-gases. We calculated method-specific age-standardised suicide
      rates by gender within each of the four age groups. We applied joinpoint
      regression to the data and quantified the observed changes. RESULTS: Suicide
      rates by domestic gas, regardless of gender and age, increased from 1968 to the
      mid-1970s and then decreased sharply. The proportion of all suicides accounted
      for by domestic gas was comparatively high in the mid-1970s among females aged 15
      24 and 25-44 years, while for other gender-age-groups the proportion of domestic
      gas suicides remained small, even at the peak. For females aged 15-44 years, the
      decrease in domestic gas suicides appeared to cause a substantial decrease in
      overall suicides in this gender/age group. Car exhaust gas was a more common
      method for males, particularly those aged 25-64 years. Car exhaust gas suicide
      rates for males aged 25-64 years peaked in the mid-1980s, followed by a sharp
      decrease. CONCLUSIONS: A reduction in the carbon monoxide content of the domestic
      gas, which began in the early 1970s in Japan, was associated with a decrease in
      domestic gas suicides for both genders of all ages. Concerning females aged 15-44
      years, a decrease in domestic gas suicides caused a substantial decrease in
      overall suicides in this gender/age group since the proportion of domestic gas
      suicides among all suicides combined was comparatively large. However, it remains
      uncertain whether the introduction of catalytic converters in the 1970s in Japan
      resulted in a reduction of suicides from car exhaust gas inhalation.

PMID- 30103841
TI  - Design of Gravel-Sand-Filter for arsenic removal: A case study of Muzaffargarh
      district in Pakistan.
AB  - Arsenic decontamination of drinking water has grabbed significant attentions due
      to its serious effects on health. A novel gravel sand filter (GSF) holding zero
      valent iron plates is designed and constructed in Muzaffargarh district
      (Pakistan) for arsenic removal from drinking water with lower iron concentration
      (0.3 ppm). The GSF efficiently removed arsenic up to 99.99% with long-term
      stability. GSF provides 800 litters arsenic-free drinking water in 39 hours with
      a rate of 2.5 L/h. Tentative mechanism for arsenic removal is evaluated and
      described on the basis of oxidation-coagulation-adsorption processes. Chemical
      composition of underground water is also analyzed and discussed. This design of
      GSF will open new avenue for arsenic removal and can be extended to other parts
      of the world.

PMID- 30103840
TI  - Cost impact of monitoring exhaled nitric oxide in asthma management.
AB  - BACKGROUND: Asthma guidelines recommend periodic assessment of impairment and
      risk factors to prevent exacerbations, which can lead to hospitalization and
      increased health care utilization and cost. According to recent meta-analysis
      data, fractional exhaled nitric oxide (FeNO) monitoring is associated with a 40
      50% reduction in the risk of exacerbations. OBJECTIVE: Cost modeling of these
      data indicates the potential for significant cost savings with FeNO use.
      Therefore, we attempted to verify this potential for cost savings within a real
      world data base of Medicare beneficiaries. METHODS: This retrospective
      observational study investigated asthma-related claims from a Medicare data base.
      Beneficiaries were included who had 2 years of records after an asthma-related
      inpatient hospitalization (IP) or emergency department (ED) claim. A case
      crossover analysis was completed of asthma-related IP or ED events before and
      after FeNO use during the 2-year study period. RESULTS: Of the 5911 asthma
      beneficiaries who met the inclusion criteria within the data base, 101 had an
      FeNO test during the 2-year study period. During the period before FeNO use, 98
      of 101 (97%) beneficiaries had an asthma-related IP or ED event compared with 46
      of 101 (46%) during the FeNO period. Asthma-related IP or ED claims and charges
      per beneficiary per day during the period before FeNO were 0.004 and $16.21
      compared with 0.002 and $6.46 during the FeNO period (p = 0.0433 and p = 0.0133,
      respectively). CONCLUSION: FeNO monitoring in beneficiaries with a history of
      exacerbations was associated with a substantial reduction in asthma-related IP
      and ED claims and charges. These data supported cost modeling estimates and
      demonstrated that FeNO use in asthma management was associated with significant
      cost savings.

PMID- 30103842
TI  - Understanding Urban Stormwater Denitrification in Bioretention 1 Internal Water
      Storage.
AB  - Conventional free-draining bioretention systems promote nitrate production and
      continual 23 leaching to receiving waters. In this study, laboratory tests
      demonstrated the efficacy of an 24 internal water storage zone (IWSZ) to target
      nitrate removal via denitrification. Experimental 25 results confirmed that the
      carbon substrate characteristics (Willow Oak woodchip media) and the 26 hydraulic
      retention time of nitrified stormwater affected nitrate removal performance. A
      2.6-day 27 batch treatment time reduced 3.0 mg-N/L to <0.01 mg/L, corresponding
      to a first-order 28 denitrification rate constant of 0.0011 min-1. Under various
      flow conditions, the associated 29 hydraulic retention time may be used as a
      predictive measurement of nitrate removal 30 performance. Scanning Electron
      Microscopy and 16S rRNA analysis of the woodchips showed that biofilms were
      present that could be responsible for anaerobic lignocellulose degradation and 32
      denitrification. This knowledge, along with evaluation of the biofilm community
      composition, 33 reinforced the notion of a heterogeneous structure due to
      nutrient availability and hydrodynamic conditions.

PMID- 30103843
TI  - Ascorbic Acid Determination Based on Electrocatalytic Behavior of Metal-Organic
      Framework MIL-101-(Cr) at Modified Carbon-Paste Electrode.
AB  - Background: Metal-organic frameworks (MOFs) are classified as microporous
      materials. They have large surface areas, low framework densities, accessible
      cages, and tunnels with modifiable pores. Objective: The MOF MIL-101(Cr) with a
      large pore volume was synthesized hydrothermally and used in the electrochemical
      reactions as an electrocatalyst for the determination of ascorbic acid (AA). The
      synthesized MOF was characterized by scanning electron microscopy and X-ray
      powder diffraction. Methods: The electrocatalytic behavior of a carbon-paste
      electrode modified with MIL-101(Cr) was studied through electro-oxidation of AA
      by cyclic voltammetry and square wave voltammetry. The conventional three
      electrode cell system, consisting of Ag/AgCl (3 M KCl) as the reference, platinum
      wire as the counter electrode, and modified carbon paste as the working
      electrode, was used in the experiment. Results: Under optimized experimental
      conditions, the electrode revealed a linear relationship between the oxidation
      peak current and concentration of AA over a wide range from 0.01 to 10 mM with
      the LOD of 0.006 mM (3 Sb/m). The results showed that 100-fold of Na+, K+, Mg2+,
      Ca2+, Cl-, SO42-, sorbitol, sucrose, fructose, citric acid, 40-fold of NO3-,
      glucose, sucrose, urea, and 10-fold of uric acid had no significant interference.
      The method was adapted for the determination of the concentration of AA present
      in two real samples (vitamin C tablet and vitamin C effervescent tablet) with
      recovery of 97.0 and 96.0%, respectively. Conclusions: A simple, sensitive and
      reliable modified electrode has been established and applied for the
      determination of AA. Highlights: The modified electrode represented a good
      performance in the analysis of the real sample.

PMID- 30103844
TI  - Resveratrol enhances cisplatin-induced apoptosis in human hepatoma cells via
      glutamine metabolism inhibition.
AB  - Cisplatin is one of the most effective chemotherapeutic drugs used in the
      treatment of HCC, but many patients will ultimately relapse with cisplatin
      resistant disease. Used in combination with cisplatin, resveratrol has
      synergistic effect of increasing chemosensitivity of cisplatin in various cancer
      cells. However, the mechanisms of resveratrol enhancing cisplatininduced toxicity
      have not been well characterized. Our study showed that resveratrol enhances
      cisplatin toxicity in human hepatoma cells via an apoptosis-dependent mechanism.
      Further studies reveal that resveratrol decreases the absorption of glutamine and
      glutathione content by reducing the expression of glutamine transporter ASCT2.
      Flow cytometric analyses demonstrate that resveratrol and cisplatin combined
      treatment leads to a significant increase in ROS production compared to
      resveratrol or cisplatin treated hepatoma cells alone. Phosphorylated H2AX
      (gammaH2AX) foci assay demonstrate that both resveratrol and cisplatin treatment
      result in a significant increase of gammaH2AX foci in hepatoma cells, and the
      resveratrol and cisplatin combined treatment results in much more gammaH2AX foci
      formation than either resveratrol or cisplatin treatment alone. Furthermore, our
      studies show that over-expression of ASCT2 can attenuate cisplatin-induced ROS
      production, gammaH2AX foci formation and apoptosis in human hepatoma cells.
      Collectively, our studies suggest resveratrol may sensitize human hepatoma cells
      to cisplatin chemotherapy via glutamine metabolism inhibition. [BMB Reports 2018;
      51(9): 474-479].

PMID- 30103845
TI  - The purinergic receptor P2X5 contributes to bone loss in experimental
      periodontitis.
AB  - Purinergic receptor signaling is increasingly recognized as an important
      regulator of inflammation. The P2X family purinergic receptors P2X5 and P2X7 have
      both been implicated in bone biology, and it has been suggested recently that
      P2X5 may be a significant regulator of inflammatory bone loss. However, a role
      for P2X5 in periodontitis is unknown. The present study aimed to evaluate the
      functional role of P2X5 in ligatureinduced periodontitis in mice. Five days after
      placement of ligature, analysis of alveolar bone revealed decreased bone loss in
      P2rx5-/- mice compared to P2rx7-/- and WT control mice. Gene expression analysis
      of the gingival tissue of ligated mice showed that IL1b, IL6, IL17a and Tnfsf11
      expression levels were significantly reduced in P2rx5-/- compared to WT mice.
      These results suggest the P2X5 receptor may regulate bone loss related to
      periodontitis and it may thus be a novel therapeutic target in this oral disease.
      [BMB Reports 2018; 51(9): 468-473].

PMID- 30103846
TI  - Oxidative stress causes Alu RNA accumulation via PIWIL4 sequestration into stress
      granules.
AB  - The Alu element, the most abundant transposable element, is transcribed to Alu
      RNA. We hypothesized that the PIWI protein regulates the expression of Alu RNA in
      retinal pigment epithelial (RPE) cells, where accumulated Alu RNA leads to
      macular degeneration. Alu transcription was induced in RPE cells treated with
      H2O2. At an early stage of oxidative stress, PIWIL4 was translocated into the
      nucleus; however, subsequently it was sequestered into cytoplasmic stress
      granules, resulting in the accumulation of Alu RNA. An elevated amount of Alu RNA
      was positively correlated with the disruption of the epithelial features of RPE
      via induction of mesenchymal transition. Therefore, we suggest that oxidative
      stress causes Alu RNA accumulation via PIWIL4 sequestration into the cytoplasmic
      stress granules.

PMID- 30103847
TI  - Defect of SIRT1-FoxO3a axis is associated with the production of reactive oxygen
      species during protein kinase CK2 downregulation-mediated cellular senescence and
      nematode aging.
AB  - We investigated whether SIRT1 is associated with reactive oxygen species (ROS)
      accumulation during CK2 downregulation-mediated senescence. SIRT1 overexpression
      suppressed ROS accumulation, reduced transcription of FoxO3a target genes, and
      nuclear export and acetylation of FoxO3a, which were induced by CK2
      downregulation in HCT116 and MCF-7 cells. Conversely, overexpression of a
      dominant-negative mutant SIRT1 (H363Y) counteracted decreased ROS levels,
      increased transcriptional activity of FoxO3a, and increased nuclear import and
      decreased acetylation of FoxO3a, which were induced by CK2 upregulation. CK2
      downregulation destabilized SIRT1 protein via an ubiquitin-proteasome pathway in
      human cells, whereas CK2 overexpression reduced ubiquitination of SIRT1. Finally,
      the SIRT1 activator resveratrol attenuated the accumulation of ROS and lipofuscin
      as well as lifespan shortening, and reduced expression of the DAF-16 target gene
      sod-3, which were induced by CK2 downregulation in nematodes. Altogether, this
      study demonstrates that inactivation of the SIRT1-FoxO3a axis, at least in part,
      is involved in ROS generation during CK2 downregulation-mediated cellular
      senescence and nematode aging.

PMID- 30103849
TI  - Amelioration by quercetin of insulin resistance and uterine GLUT4 and ERalpha
      gene expression in rats with polycystic ovary syndrome (PCOS).
AB  - Insulin resistance (IR) and infertility are two major complications of polycystic
      ovary syndrome (PCOS), which are the results of changes in certain parts of the
      reproductive and metabolic systems. We aimed to observe the effect of quercetin
      on dehydroepiandrosterone (DHEA)-induced PCOS and insulin resistance in rats. All
      animals were divided into five groups and DHEA was used to induce PCOS.
      Bodyweight and ovarian morphology of all groups were observed. Fasting blood
      glucose and insulin levels were analysed. The homeostasis model assessment of
      insulin resistance (HOMA-IR) method was used for IR level determination. The
      expression of oestrogen receptor alpha (ERalpha) and glucose transporter 4
      (GLUT4) genes in the uterus was examined by real-time polymerase chain reaction.
      Liver hexokinase (HK) and glucokinase (GK) activity was determined using
      spectrophotometry. Quercetin significantly improved the IR state in PCOS rats.
      PCOS resulted in a decrease in liver GK and an increase in liver HK specific
      activity, whereas quercetin increased both liver HK and GK activity. Our data
      also showed a significant reduction in uterine ERalpha and GLUT4 expression in
      the PCOS group, which was increased by quercetin. A remarkable effect of
      quercetin was the intensive reduction of PCOS-IR and significant induction of
      uterine GLUT4 and ERalpha gene expression; it could thus be a possible effective
      treatment for PCOS and its complications, IR and infertility.

PMID- 30103850
TI  - Resuscitation status in psychogeriatric and general medical inpatients aged 65
      years and older: a retrospective comparison study.
AB  - Objective The aims of the present study were to establish rates of resuscitation
      order documentation of patients aged >=65 years from both psychogeriatric and
      general medical units and to compare patients on predictors of resuscitation
      status, particularly examining the effect of depression.Methods A retrospective
      case note audit of psychogeriatric (n = 162) and general medical (n = 135) unit
      admissions within a tertiary teaching hospital was performed. Multivariate
      logistic regression was used to determine significant clinical and demographic
      predictors of resuscitation status.Results Resuscitation orders were documented
      in more psychogeriatric (94.4%) than general medical (48.1%) files. Depression
      did not significantly predict resuscitation status in either group. Having
      undergone competency assessment significantly predicted resuscitation status for
      the total sample and separately for psychogeriatric and medical patients. Older
      age (overall sample), poorer prognosis (overall sample), living in residential
      care (overall sample and medical group) and self-consenting to resuscitation
      status (overall sample and medical group) significantly predicted resuscitation
      status.Conclusions Resuscitation orders were more frequently documented on the
      psychogeriatric unit. Further prospective analysis is needed of how resuscitation
      orders are made before depression is discounted as a predictor of end-of-life
      decision-making.What is known about the topic? Despite increased community, media
      and research attention to end-of-life decision-making, resuscitation preferences
      of older patients are often poorly documented. Existing research into patient
      clinical and demographic factors that influence end-of-life decision-making have
      largely focused on general medical rather than psychogeriatric settings. There is
      a need to investigate rates of resuscitation documentation in psychogeriatric and
      general medical units and specific factors associated with having a 'do not
      attempt resuscitation' order in place, particularly the effect of current
      depression on decision-making.What does this paper add? Resuscitation orders were
      more frequently documented on the psychogeriatric than medical unit. Depression
      was not a significant predictor of resuscitation status in either group of
      patients. Although having undergone a competency assessment, older age and poorer
      prognosis predicted not being for resuscitation for the total sample, living in
      residential care and self-consenting to resuscitation status predicted not being
      for resuscitation for the overall sample and the medical group specifically.What
      are the implications for practitioners? This paper suggests that the need for
      clinicians to ensure documentation of preferences is a focus of day-to-day work
      with older patients. Clinicians should consider patient competency in end-of-life
      decision-making and how factors associated with depression, such as helplessness,
      may be more closely related to resuscitation decision-making in older patients.

PMID- 30103848
TI  - The road less traveled: strategies to enhance the frequency of homology-directed
      repair (HDR) for increased efficiency of CRISPR/Cas-mediated transgenesis.
AB  - Non-homologous end joining (NHEJ), and to a lesser extent, the error-free pathway
      known as homology-directed repair (HDR) are cellular mechanisms for recovery from
      double-strand DNA breaks (DSB) induced by RNA-guided programmable nuclease
      CRISPR/Cas. Since NHEJ is equivalent to using a duck tape to stick two pieces of
      metals together, the outcome of this repair mechanism is prone to error. Any out
      of-frame mutations or premature stop codons resulting from NHEJ repair mechanism
      are extremely handy for loss-of-function studies. Substitution of a mutation on
      the genome with the correct exogenous repair DNA requires coordination via an
      error-free HDR, for targeted transgenesis. However, several practical limitations
      exist in harnessing the potential of HDR to replace a faulty mutation for
      therapeutic purposes in all cell types and more so in somatic cells. In germ
      cells after the DSB, copying occurs from the homologous chromosome, which
      increases the chances of incorporation of exogenous DNA with some degree of
      homology into the genome compared with somatic cells where copying from the
      identical sister chromatid is always preferred. This review summarizes several
      strategies that have been implemented to increase the frequency of HDR with a
      focus on somatic cells. It also highlights the limitations of this technology in
      gene therapy and suggests specific solutions to circumvent those barriers. [BMB
      Reports 2018; 51(9): 437-443].

PMID- 30103851
TI  - Partner violence and postnatal mental health: cross-sectional analysis of factors
      associated with depression and anxiety in new mothers.
AB  - Intimate-partner violence and poor mental health are common, harmful issues for
      women of childbearing age. Although the prevalence and correlates of postpartum
      depression are well established, far less is known about postpartum anxiety. We
      aimed to investigate the association between postnatal depression and anxiety,
      and intimate-partner violence among women attending Victorian Maternal and Child
      Health services, using data from a randomised control trial: Improving Maternal
      and Child Health care for Vulnerable Mothers (MOVE). These data included
      postnatal women who had given birth between May and December 2010. Multiple
      logistic regression was used to estimate the association between intimate partner
      violence (using the Composite Abuse Scale) and postnatal depression and anxiety
      (Depression, Anxiety and Stress Scale), controlling for participant socio
      demographic characteristics. Findings showed that abused women were more likely
      to report postnatal depressive and anxiety symptoms. There was an almost two-fold
      (odds ratio (OR) 1.76, 95% CI 1.03-3.01) and three-fold (OR 2.6, 95% CI 1.58
      4.28) increase in the odds of reporting depressive and anxiety symptoms
      respectively, among abused compared with non-abused women. Abused women are at a
      higher risk of mental health problems. This study validated findings that
      intimate-partner violence is strongly associated with an increased risk of
      postnatal depression and highlighted the previously under-reported relationship
      with postnatal anxiety.

PMID- 30103852
TI  - A narrative review and synthesis to inform health workforce preparation for the
      Health Care Homes model in primary healthcare in Australia.
AB  - The Australian Government Health Care Homes (HCH) model recently implemented in
      general practice targets people with chronic complex conditions. Identifying how
      general practitioners (GPs) and practice nurses (PNs) can work within this model
      is important given existing health workforce challenges. A narrative review and
      synthesis has been undertaken to develop a preliminary understanding of this,
      incorporating literature describing health workforce challenges, GP and PN
      functions, and team-based care; supplemented by interviews with key informants
      from within the primary healthcare system. Narrative synthesis principles guided
      literature analysis. Interview data were thematically analysed. A clear rationale
      for health workforce reform was ascertained and functions for the GP and PN under
      the HCH model were determined. The model was found to be an opportunity for an
      enhanced PN role in a team-based approach to care with the GP. Challenges to
      advancing the PN role and team-based care were identified, including the medical
      dominance of the health system and the significant culture change required by
      general practices to fully implement the model. Enablers included strong nursing
      leadership and improved ongoing education for PNs to unlock their capacity. The
      HCH model is an opportunity to strengthen primary healthcare, provided concerted
      action is taken regarding these challenges and enablers.

PMID- 30103853
TI  - Teaching Case 5-2018: Integrated morphological and immunological work-up of
      neurosurgical specimen allows accurate diagnosis of neuroinflammatory lesions: an
      example of acute disseminated encephalomyelitis (ADEM) associated with anti-MOG
      antibodies.

PMID- 30103854
TI  - Using paired serology and surveillance data to quantify dengue transmission and
      control during a large outbreak in Fiji.
AB  - Dengue is a major health burden, but it can be challenging to examine
      transmission and evaluate control measures because outbreaks depend on multiple
      factors, including human population structure, prior immunity and climate. We
      combined population-representative paired sera collected before and after the
      2013/14 dengue-3 outbreak in Fiji with surveillance data to determine how such
      factors influence transmission and control in island settings. Our results
      suggested the 10-19 year-old age group had the highest risk of infection, but we
      did not find strong evidence that other demographic or environmental risk factors
      were linked to seroconversion. A mathematical model jointly fitted to
      surveillance and serological data suggested that herd immunity and seasonally
      varying transmission could not explain observed dynamics. However, the model
      showed evidence of an additional reduction in transmission coinciding with a
      vector clean-up campaign, which may have contributed to the decline in cases in
      the later stages of the outbreak.

PMID- 30103855
TI  - The newly-arisen Devil facial tumour disease 2 (DFT2) reveals a mechanism for the
      emergence of a contagious cancer.
AB  - Devil Facial Tumour 2 (DFT2) is a recently discovered contagious cancer
      circulating in the Tasmanian devil (Sarcophilus harrisii), a species which
      already harbours a more widespread contagious cancer, Devil Facial Tumour 1
      (DFT1). Here we show that in contrast to DFT1, DFT2 cells express major
      histocompatibility complex (MHC) class I molecules, demonstrating that loss of
      MHC is not necessary for the emergence of a contagious cancer. However, the most
      highly expressed MHC class I alleles in DFT2 cells are common among host devils
      or non-polymorphic, reducing immunogenicity in a population sharing these
      alleles. In parallel, MHC class I loss is emerging in vivo, thus DFT2 may be
      mimicking the evolutionary trajectory of DFT1. Based on these results we propose
      that contagious cancers may exploit partial histocompatibility between the tumour
      and host, but that loss of allogeneic antigens could facilitate widespread
      transmission of DFT2.

PMID- 30103856
TI  - Dynamic density shaping of photokinetic E. coli.
AB  - Many motile microorganisms react to environmental light cues with a variety of
      motility responses guiding cells towards better conditions for survival and
      growth. The use of spatial light modulators could help to elucidate the
      mechanisms of photo-movements while, at the same time, providing an efficient
      strategy to achieve spatial and temporal control of cell concentration. Here we
      demonstrate that millions of bacteria, genetically modified to swim smoothly with
      a light controllable speed, can be arranged into complex and reconfigurable
      density patterns using a digital light projector. We show that a homogeneous sea
      of freely swimming bacteria can be made to morph between complex shapes. We model
      non-local effects arising from memory in light response and show how these can be
      mitigated by a feedback control strategy resulting in the detailed reproduction
      of grayscale density images.

PMID- 30103858
TI  - Physicochemical characterisation in drug discovery.

PMID- 30103857
TI  - A 'devil' of a problem.
AB  - The discovery of a second facial tumor disease in the Tasmanian devil has
      provided insights into the emergence of contagious cancers.

PMID- 30103859
TI  - Automated assays for thermodynamic (equilibrium) solubility determination.
AB  - Solubility is a crucial physicochemical property for drug candidates and is
      important in both drug discovery and development. Poor solubility is detrimental
      to absorption after oral administration and can mask compound activity in
      bioassays in various ways. Hence, solubility liabilities should ideally be
      identified as early as possible in the drug development process. With the
      increasing number of compounds as potential drug candidates, automated
      thermodynamic solubility assays for high throughput screening enabling rapid
      evaluation of a large number of compounds are becoming increasingly important.
      This review discusses the current status of the most widely used automated assays
      for thermodynamic solubility, followed by recent high throughput measurements of
      properties related to solubility (e.g. dissolution rate and supersaturation) and
      a brief overview of predictive computational methods for thermodynamic solubility
      reported in the literature.

PMID- 30103860
TI  - Different types, applications and limits of enabling excipients of pharmaceutical
      dosage forms.
AB  - Along with the development of novel drug delivery systems the material science is
      also advancing. Conventional and novel synthetic or natural excipients provide
      opportunities to design dosage forms of the required features including their
      bioavailability. Emerging trends in the design and development of drug products
      indicate an increasing need for the functionality-related characterization of
      excipients. The purpose of this review is to provide an overview of different
      types of excipients in relation to their application possibilities in various
      dosage forms with special focus on the enabling excipients. The study also
      summarizes the applied excipient systems of research formulations and dosage
      forms available on the market.

PMID- 30103861
TI  - Brief overview of solubility methods: Recent trends in equilibrium solubility
      measurement and predictive models.
AB  - Solubility is a crucial physicochemical parameter affecting the whole process of
      drug discovery and development. Thus, understanding of the methods and concepts
      to measure and predict this propensity are of utmost importance for the
      pharmaceutical scientist. Despite their inherent limitations, kinetic solubility
      screening methods became routine assays by mimicking bioassay conditions and
      guiding the lead optimization process. In contrast, thermodynamic solubility
      methods show a clear evolution: miniaturized high throughput assays coupled to
      analytical techniques such as solid-state characterization, ultra performance
      liquid chromatography, or polychromatic turbidimetry, have been developed,
      thereby enabling a more complex physicochemical profiling at the early discovery
      stage. Solubility prediction still poses a significant challenge at the
      industrial level. Classification and critical evaluation of recent in silico
      models are provided. Discussion of experimental and computational methods: was
      based on relevant industrial references.

PMID- 30103862
TI  - The influence and manipulation of acid/base properties in drug discovery.
AB  - There is a growing awareness of the importance of acid/base properties in
      medicinal chemistry research. In many drug classes, ionisable groups are present
      that make critical interactions with the receptor and are essential for potency.
      Yet the presence of these groups may cause problems with oral bioavailability,
      pharmacokinetics, or toxicity. Manipulating pKa values during drug development or
      applying pro-drug techniques are strategies that can overcome potential deficits
      in a variety of these areas. Knowledge of drug ionisation states coupled with a
      consideration of pH-specific cellular environments can be used advantageously to
      target chemoresistance. As modern drug research ventures into drug candidates
      that exceed the rule of 5, such exploration requires an understanding of drug
      acid/base properties and how these factors affect ADMET characteristics.

PMID- 30103863
TI  - Automated techniques in pKa determination: Low, medium and high-throughput
      screening methods.
AB  - Drug discovery programs that generate hundreds of new molecular entities need
      efficient methodologies for physicochemical profiling. Several high-throughput
      methods for pKa screening have been developed in the last 15 years to determine
      this key physicochemical parameter. Separation techniques such as HPLC-MS or
      capillary electrophoresis are particularly well-suited due to their high
      throughput and capacity to deal with impure or complex samples. In addition,
      potentiometric and (mostly) UV-metric-based methods (plate-based and automated
      systems), find their place as very precise methodologies for pKa determination
      despite of somewhat lower throughput. Finally, pKa prediction software packages
      are useful estimator tools but, to date, they cannot replace experimental
      measurements when accurate pKa values are required.

PMID- 30103864
TI  - Experimental and pKa prediction aspects of tautomerism of drug-like molecules.
AB  - Molecules that can tautomerize are a challenge to scientists because one must
      consider the possible tautomers in most tasks involving chemical structures: for
      example, searching databases, interpreting experimental property measurements,
      calculating properties, virtual screening, and analyzing structure-bioactivity
      relationships. The challenge in interpreting property measurements such as pKa
      values feeds into the general lack of extensive information not only of the
      relative tautomer stability in water but also the properties of the individual
      tautomers. This lack of information results in the lack of reliability of
      computational predictions of tautomer stability or properties. In spite of these
      problems, pKa calculations are reliable enough that they can be used to filter
      out high-energy tautomers from databases used for virtual screening. Continuous
      improvements in both pKa prediction software and theoretical calculations promise
      further improvements in solving the challenges of tautomers. The expected
      availability of high-resolution structures of many more tautomer-protein
      complexes will help guide the selection of the bioactive tautomer when the
      structure of the complex is not known.

PMID- 30103865
TI  - Log P as a tool in intramolecular hydrogen bond considerations.
AB  - Intramolecular hydrogen bonding (IMHB) considerations are gaining relevance in
      drug discovery and a molecular descriptor which can predict very early the
      capacity of a compound to form IMHB is needed to speed up the optimization
      process of drug candidates. Although log Poct is largely used for optimization
      purposes, in this paper we firstly use the Block Relevance (BR) analysis to
      theoretically show how log Poct is not a convenient choice to assess IMHB
      properties of candidates. Then we discuss the limits of log Poct and introduce
      Deltalog Poct-tol, i.e. the difference between log Poct and log Ptol (the
      logarithm of the partition coefficient in the toluene/water system). Finally, we
      provided some examples also including bRo5 protease inhibitors, to clarify how to
      interpret Deltalog Poct-tol values.

PMID- 30103866
TI  - Matrix systems for oral drug delivery: Formulations and drug release.
AB  - In this current article matrix formulations for oral drug delivery are reviewed.
      Conventional dosage forms and novel applications such as 3D printed matrices and
      aerogel matrices are discussed. Beside characterization, excipients and matrix
      forming agents are also enlisted and classified. The incorporated drug could
      exist in crystalline or in amorphous forms, which makes drug dissolution easily
      tunable. Main drug release mechanisms are detailed and reviewed to support
      rational design in pharmaceutical technology and manufacturing considering the
      fact that R&D members of the industry are forced to obtain knowledge about
      excipients and methods pros and cons. As innovative and promising research fields
      of drug delivery, 3D printed products and highly porous, low density aerogels
      with high specific surface area are spreading, currently limitlessly. These
      compositions can also be considered as matrix formulations.

PMID- 30103867
TI  - Physico-chemical characterization of self-emulsifying drug delivery systems.
AB  - Self-emulsifying drug delivery systems (SEDDS) are regarded as a potential
      implement for oral delivery of water insoluble APIs to overcome their poor and
      irregular bioavailability. The correlation between the physicochemical parameters
      and the behavior of self-emulsifying drug delivery systems was established. The
      objective of this study was to summarize these physicochemical factors
      characterized SEDDS. Determination of self-emulsification process and ternary
      phase diagram are the basis of preparations. The position of APIs in SEDDS
      inclusion can be determined by dye solubilisation test. The end point of self
      emulsification was controlled by turbimetric evaluation. Optimisation of droplet
      size and zeta potential are crucial parameters because they can influence i.e.
      the dissolution rate of APIs and the stability of SEDDS. Besides the basic
      methods in the characterization of SEDDS such as dispersibility tests,
      turbidimetric evaluation, viscosity tests, determinations with complex
      instruments such as photon correlation spectroscopy or dynamic light-scattering,
      electro kinetic potential measurement, non-destructive spectroscopic techniques
      (LFDS, FTIR, RS) and various microscopic techniques (SEM, PLM, EDS) has also been
      described.

PMID- 30103868
TI  - Modifying the physicochemical properties of NSAIDs for nasal and pulmonary
      administration.
AB  - This review focuses on nasal and pulmonary delivery of NSAIDs (non-steroidal anti
      inflammatory drugs) for fast-onset analgesia, for the potential prevention of
      Alzheimer's disease (AD), as well as for an add-on treatment in cystic fibrosis
      (CF) and non-small cell lung cancer (NSCLC). I discuss how the physicochemical
      properties of NSAIDs can be modified with respect to the biological
      characteristics of the target site. Innovative technology and/or dosage forms can
      promote an effective therapy.

PMID- 30103870
TI  - Tuberculosis in Pregnancy: A Treacherous Yet Neglected Issue.

PMID- 30103869
TI  - Targeting macrophages for cancer therapy disrupts bone homeostasis and impairs
      bone marrow erythropoiesis in mice bearing Lewis lung carcinoma tumors.
AB  - Macrophages are represented in all tissues by phenotypically distinct resident
      populations that show great functional diversity. Macrophages generally play a
      protumoral role, and they are attractive targets for cancer therapy. In this
      study, we found that CD169+ macrophages depletion inhibited the growth of
      established Lewis lung carcinoma tumors in mice. Benefits must be weighed against
      potential adverse effects in cancer therapy. Here, we investigated the adverse
      effects of CD169+ macrophages depletion on bone and bone marrow in mice bearing
      Lewis lung carcinoma tumors. Our studies showed that depletion of CD169+
      macrophages in LLC tumor-bearing mice disrupted bone homeostasis, including bone
      weight loss and bone mineral density decrease. Further studies revealed that bone
      marrow erythropoiesis was severely impaired after depletion of CD169+ macrophages
      in LLC tumor-bearing mice. Our findings suggest that depletion of macrophages for
      cancer therapy may be associated with potential adverse effects that need to be
      recognized, prevented, and optimally managed.

PMID- 30103871
TI  - Excerpts from World Medical Literature: Obstetrics.

PMID- 30103872
TI  - Extraits de la litterature medicale mondiale: obstetrique.

PMID- 30103873
TI  - Learning From Experience: Development of a Cognitive Task List to Perform a
      Caesarean Section for the Preterm Growth-Restricted Fetus.

PMID- 30103874
TI  - The Sustained Value of an Early Pregnancy Assessment Clinic in the Management of
      Early Pregnancy Complications: A 10-Year Retrospective Study.
AB  - OBJECTIVE: This study sought to evaluate the sustained value of an early
      pregnancy assessment clinic (EPAC) in the management of early pregnancy
      complications and its effect on the incidence emergency room (ER) visits.
      METHODS: A 10-year retrospective study (January 2006 to December 2015) was
      conducted. The number of patients assessed, sources and reasons for referral, and
      treatments provided were reviewed. The numbers of ER assessments and
      reassessments for abortion, hemorrhage, and ectopic pregnancy from January 2004
      to December 2005 (pre-EPAC) and January 2006 to December 2015 (post-EPAC) were
      also reviewed. RESULTS: There were 11 349 new referrals and 10 764 follow-up
      visits. The reasons for referral were threatened miscarriage (n = 3568, 31.4%),
      missed miscarriage (n = 3056, 26.9%), incomplete miscarriage (n = 1064, 9.4%),
      complete miscarriage (n = 991, 8.7%), ectopic pregnancy (n = 857, 7.6%),
      hyperemesis gravidarum (n = 139, 1.2%), and others (n = 1674, 14.8%). There has
      been a significant decreasing trend (tau = -0.60, P = 0.0127) and a significant
      decrease in the post-EPAC rate of ER reassessments (P = 0.0396) for hemorrhage,
      with a concomitant decrease in EPAC visits for hemorrhage. In addition, there has
      been a significant increasing trend (tau = 0.64, P = 0.0081) and a significant
      increase in the post-EPAC rate of ER assessments (P = 0.00001) for ectopic
      pregnancies. CONCLUSION: Over the 10-year period, the EPAC has remained a vital
      service for managing early pregnancy complications for women. However, the clinic
      has not yet had a sustained impact on ER visits for miscarriage, ectopic
      pregnancy, and hemorrhage. It is possible that a reduction in ER assessments and
      reassessments for early pregnancy complications can be achieved through a clinic
      with daily access.

PMID- 30103875
TI  - Interpregnancy Intervals in a Contemporary Manitoba Cohort: Prevalence of So
      Called Suboptimal Intervals and Associated Maternal Characteristics.
AB  - OBJECTIVE: Short and long interpregnancy intervals (IPIs) have been associated
      with various adverse outcomes, and a 2016 American College of Obstetricians and
      Gynecologists' Committee Opinion recommends an optimal IPI of 18 months to 5
      years. Descriptive data on the IPI in Canada are lacking. The objective of this
      study was to examine IPIs in a Manitoba cohort. METHODS: The study analyzed a
      subset of records from a larger dataset used to examine the IPI and adverse
      perinatal outcomes. For that study, Manitoba's Hospital Abstracts data were
      searched to identify births from 1985 to 2014. Each two consecutive live births
      to the same mother formed a sibling pair. The IPI was calculated as the interval
      between the two siblings' births, minus the younger sibling's GA. Information on
      maternal characteristics was extracted from various datasets housed in the
      Manitoba Population Research Data Repository. The current analysis examined
      second and higher-order births between 2010 and 2014. The proportion of
      suboptimal IPIs was determined and IPIs were cross-tabulated with birth year and
      maternal subgroups. RESULTS: More than half of pregnancies were conceived
      following a suboptimal interval. IPIs of less than 6 months - which have been
      associated with the highest risk of adverse outcomes - were more prevalent among
      certain subgroups. These included younger women as well as women who received
      inadequate prenatal care, smoked or drank alcohol during pregnancy, were low
      income, or did not graduate from high school. CONCLUSION: Suboptimal IPIs were
      common in this Manitoba cohort. Stakeholders should consider whether greater
      efforts to promote appropriate birth spacing are warranted.

PMID- 30103876
TI  - Prevalence of Low Back Pain, Pelvic Girdle Pain, and Combination Pain in a
      Pregnant Ontario Population.
AB  - OBJECTIVE: The purpose of the current pilot study is to determine the point and
      period prevalence of site-specific back pain, low back pain (LBP), pelvic girdle
      pain (PGP), and combined pain (Combo Pain) in pregnant women at a large urban
      centre in Ontario. METHODS: Point and period prevalence for LBP, PGP, and Combo
      Pain were determined using a questionnaire and accompanying pain diagram. Women
      were included in the study if they were healthy, of child-bearing age (18-45
      years), currently experiencing a singleton pregnancy (any trimester), and
      proficient in the English language. RESULTS: Data collected from 287 women were
      included in the analysis. Three-quarters of women suffered from some sort of
      pregnancy-related back pain. The point and period prevalences for women who were
      experiencing LBP, PGP, and Combo Pain were 15.7%, 17.8%, and 15.3% and 33.4%,
      27.9%, and 30.7%, respectively. Secondary analyses demonstrated that increasing
      GA and suffering from both pains at some point prior to pregnancy (Prior Both)
      increased the risk of experiencing PGP and Combo Pain during pregnancy,
      respectively. CONCLUSION: The current study demonstrates that 76% of sampled
      women experienced pregnancy-related back pain and the prevalence of site-specific
      pain (LBP, PGP, and Combo Pain) increases with increased gestation. Risk factors
      include advanced GA and experiencing both types of pain prior to pregnancy (Prior
      Both). Furthermore, it is suggested that a standard definition of pain by
      location should be developed and employed so that future studies can elucidate
      appropriate prevention strategies and treatment options for each.

PMID- 30103877
TI  - First Trimester Screening for Fetal Aneuploidies Using Placental Growth Factor:
      The Great Obstetrical Syndrome (GOS) Study.
AB  - OBJECTIVE: This study sought to estimate the ability of first trimester maternal
      serum placental growth factor (PlGF) to identify fetal aneuploidies. METHODS: A
      prospective cohort study of singleton pregnancy at 11 to 13 weeks was conducted.
      Maternal serum PlGF concentration was measured using BRAHMS PlGF plus KRYPTOR
      automated assays (Thermo Scientific BRAHMS, Hennigsdorf, Germany). PlGF and
      nuchal translucency were log-transformed and reported as multiples of the median
      (MoM) adjusted for crown-rump length. Detection rates were calculated using
      receiver-operator characteristic curves. RESULTS: The study observed 21 cases of
      fetal aneuploidies (0.4%) out of 4765 participants. Trisomy 21 (13 cases; 0.85
      MoM; interquartile range [IQR] 0.80-0.93), trisomy 18 (two cases; 0.77 MoM; IQR
      0.66-0.87) and trisomy 13 (two cases; 0.68 MoM; IQR 0.61-0.75) were associated
      with low PlGF concentrations. The low PlGF values observed in the cases of
      monosomy X (two cases; 0.85 MoM; IQR 0.82-0.88, P = 0.05), triploidy (0.78 MoM, P
      = 0.11), and 47,XX,i(22)(p10) (0.18 MoM, P = 0.08) were not statistically
      different from the controls. A model including maternal age, nuchal translucency,
      and PlGF could have identified all (95% CI 83%-100%) cases of trisomy 21 and six
      of the other fetal aneuploidies (75%) at a false-positive rate of 9%. CONCLUSION:
      Low first trimester PlGF is associated with an increased risk of fetal
      aneuploidy. PlGF combined with first trimester ultrasound (nuchal translucency,
      uterine artery Doppler, and early fetal anatomy) could identify not only women at
      high risk for preeclampsia, but also fetuses at high risk of aneuploidy for
      optimal further testing (non-invasive testing for common aneuploidy screening or
      chorionic villus sampling for full screening and diagnosis).

PMID- 30103878
TI  - A Comparison of the Number of Patient Visits Required for Different Management
      Options for Early Pregnancy Loss at an Early Pregnancy Assessment Clinic.
AB  - OBJECTIVE: To compare the total number of patient visits required for the
      conservative, medical, or surgical management of early pregnancy loss in an early
      pregnancy assessment clinic (EPAC). METHODS: A retrospective study of the number
      of patient visits at an EPAC for conservative, medical, or surgical management of
      early spontaneous abortion from October 2013 to September 2015 was undertaken.
      Visits counted included initial assessment, follow-up visits, and surgery date,
      if separate from a clinic visit. RESULTS: A total of 945 patients were seen, with
      2144 visits during the study period. Conservative management required an average
      of 3.01 visits (n = 159, median = 3, SD = 1.16, range [1,7]) and misoprostol
      treatment required an average of 2.51 visits (n = 329, median = 2, SD = 0.83,
      range [1,6]) to achieve a complete abortion. Dilatation and curettage (D&C)
      required an average of 1.60 visits (n = 417, median = 1, SD = 0.80, range [1-6]),
      when including scheduling limitations or an average of 1.13 visits when excluding
      these limitations. The difference in the number of visits required for the three
      management options was statistically significant (P <0.0001). Management with D&C
      was more likely to require less than two visits to achieve complete abortion
      compared with the other options (93.8% for D&C vs. 64.5% for misoprostol vs.
      37.8% for conservative). CONCLUSION: An EPAC provides a significant value in the
      management of early pregnancy losses. There is a significant difference in the
      total number of visits required for different treatment options. Patients may
      find this information helpful when considering and deciding upon their preferred
      treatment option.

PMID- 30103879
TI  - Should Caesarian Section Be Offered to Women With Recurrent Genital Herpes
      Simplex Lesions After >4 Hours of Ruptured Membranes?
AB  - BACKGROUND: Neonatal herpes simplex virus (HSV) infection and its implications
      have been well defined. Several methods are recommended to mitigate the risk of
      maternal transmission of HSV to the neonate, including CS, suppressive antiviral
      therapy for the mother, and prophylaxis for the infant. The utility of CS in
      women who present with a duration of rupture of membranes greater than 4 hours
      remains a question. CASE: We present a case of a woman who presented following 10
      hours of rupture of membranes with HSV genital lesions, suspected to be the
      result of untreated recurrent infection. A CS was done. CONCLUSION: Extensive
      studies for the presence of HSV by PCR of the placenta and infant failed to
      detect the virus.

PMID- 30103880
TI  - Bisexuality: The Invisible Sexual Orientation in Sexual and Reproductive Health
      Care.

PMID- 30103881
TI  - Pregnancy Outcomes Following Ulipristal Acetate for Uterine Fibroids: A
      Systematic Review.
AB  - OBJECTIVE: To determine pregnancy and fetal outcomes following treatment with
      ulipristal acetate (UPA) for symptomatic uterine fibroids. METHODS: We conducted
      a systematic review and case series. We searched MEDLINE, EMBASE, PubMed, Web of
      Science, and Cochrane Register from inception to February 2017. From January 2014
      to July 2017, we carried out a multi-centre retrospective chart review. All human
      studies that reported at least one pregnancy following UPA treatment were
      included. The case series included patients who conceived during/following UPA
      treatment. Titles and abstracts were screened for eligibility by two independent
      reviewers, and full texts were evaluated for inclusion and study quality. Data
      from the systematic review and case series were synthesized and reported
      separately. RESULTS: Seven studies were included (six case reports, one
      retrospective series) and contributed 24 post-UPA pregnancies (19 live births,
      six spontaneous abortions [SA]). The case series contributed 47 post-UPA
      pregnancies (31 live births, 13 SA, 1 fetal death, 2 terminations, 1 ongoing). In
      total, 71 pregnancies were evaluated (44 underwent myomectomy post-UPA; 27
      without interval surgery). Five pregnancies occurred during UPA use (10-36 days
      of exposure) and resulted in three live births, one SA, and one termination. Five
      women who did not undergo interval myomectomy experienced delivery complications
      related to their fibroid. CONCLUSIONS: This is the first systematic review and
      largest reported case series evaluating pregnancy outcomes following UPA
      treatment for uterine fibroids. UPA alone, or in conjunction with surgery, can
      permit conception and favorable pregnancy outcomes.

PMID- 30103882
TI  - No. 363-Investigation and Management of Non-immune Fetal Hydrops.
AB  - OBJECTIVE: To describe the current investigation and management of non-immune
      fetal hydrops with a focus on treatable or recurring etiologies. OUTCOMES: To
      provide better counselling and management in cases of prenatally diagnosed non
      immune hydrops. EVIDENCE: Published literature was retrieved through searches of
      PubMed or MEDLINE, CINAHL, and The Cochrane Library in 2017 using key words (non
      immune hydrops fetalis, fetal hydrops, fetal therapy, fetal metabolism). Results
      were restricted to systematic reviews, randomized controlled trials/controlled
      clinical trials, observational studies, and significant case reports. Additional
      publications were identified from the bibliographies of these articles. There
      were no date or language restrictions. Searches were updated on a regular basis
      and incorporated in the guideline to September 2017. Grey (unpublished)
      literature was identified through searching the websites of health technology
      assessment and health technology-related agencies, clinicalpractice guideline
      collections, clinical trial registries, and national and international medical
      specialty societies. BENEFITS, HARMS, AND COSTS: These guidelines educate readers
      about the causes of non-immune fetal hydrops and its prenatal counselling and
      management. It also provides a standardized approach to non-immune fetal hydrops,
      emphasizing the search for prenatally treatable conditions and recurrent genetic
      etiologies. VALUES: The quality of evidence in this document was rated using the
      criteria described in the Report of the Canadian Task Force on Preventive Health
      Care. RECOMMENDATIONS: 

PMID- 30103883
TI  - Correction.

PMID- 30103884
TI  - Correction.

PMID- 30103885
TI  - No. 203-Rubella in Pregnancy.
AB  - OBJECTIVE: To provide an update on rubella and pregnancy so that health
      professionals remain aware of the potentially devastating effects on the
      developing fetus. OUTCOMES: Rubella vaccination has been effective in virtually
      eliminating congenital rubella syndrome in Canada. EVIDENCE: Medline, PubMed, and
      Cochrane Database were searched for articles published between 1985 and 2007.
      VALUES: The quality of evidence was rated using the criteria described in the
      report of the Canadian Task Force on Preventive Health Care. SPONSOR: The Society
      of Obstetricians and Gynaecologists of Canada. RECOMMENDATIONS: 

PMID- 30103886
TI  - No 203-Rubeole au cours de la grossesse.

PMID- 30103887
TI  - No. 239-Obesity in Pregnancy.
AB  - OBJECTIVE: To review the evidence and provide recommendations for the counselling
      and management of obese parturients. OUTCOMES: Outcomes evaluated include the
      impact of maternal obesity on the provision of antenatal and intrapartum care,
      maternal morbidity and mortality, and perinatal morbidity and mortality.
      EVIDENCE: Literature was retrieved through searches of Statistics Canada,
      Medline, and The Cochrane Library on the impact of obesity in pregnancy on
      antepartum and intrapartum care, maternal morbidity and mortality, obstetrical
      anaesthesia, and perinatal morbidity and mortality. Results were restricted to
      systematic reviews, randomized controlled trials/controlled clinical trials, and
      observational studies. There were no date or language restrictions. Searches were
      updated on a regular basis and incorporated in the guideline to April 2009. Grey
      (unpublished) literature was identified through searching the websites of health
      technology assessment and health technology assessment-related agencies, clinical
      practice guideline collections, clinical trial registries, and national and
      international medical specialty societies. VALUES: The evidence obtained was
      reviewed and evaluated by the Maternal Fetal Medicine and Clinical Practice
      Obstetric Committees of the SOGC under the leadership of the principal authors,
      and recommendations were made according to guidelines developed by the Canadian
      Task Force on Preventive Health Care. BENEFITS, HARMS, AND COSTS: Implementation
      of the recommendations in this guideline should increase recognition of the
      issues clinicians need to be aware of when managing obese women in pregnancy,
      improve communication and consultation amongst the obstetrical care team, and
      encourage federal and provincial agencies to educate Canadians about the values
      of entering pregnancy with as healthy a weight as possible. RECOMMENDATIONS: 

PMID- 30103888
TI  - N degrees  239 - Obesite et grossesse.

PMID- 30103889
TI  - No. 274-Management of Varicella Infection (Chickenpox) in Pregnancy.
AB  - OBJECTIVE: To review the existing data regarding varicella zoster virus infection
      (chickenpox) in pregnancy, interventions to reduce maternal complications and
      fetal infection, and antepartum and peripartum management . METHODS: The maternal
      and fetal outcomes in varicella zoster infection were reviewed, as well as the
      benefit of the different treatment modalities in altering maternal and fetal
      sequelae. EVIDENCE: Medline was searched for articles and clinical guidelines
      published in English between January 1970 and November 2010. VALUES: The quality
      of evidence was rated using the criteria described in the Report of the Canadian
      Task Force on Preventive Health Care. Recommendations for practice were ranked
      according to the method described in that report (Table). RECOMMENDATIONS: 

PMID- 30103890
TI  - No 274 - Prise en charge de l'infection a la varicelle pendant la grossesse.

PMID- 30103891
TI  - No. 298-The Prevention of Early-Onset Neonatal Group B Streptococcal Disease.
AB  - OBJECTIVE: To review the evidence in the literature and to provide
      recommendations on the management of pregnant women in labour for the prevention
      of early-onset neonatal group B streptococcal disease. The key revisions in this
      updated guideline include changed recommendations for regimens for antibiotic
      prophylaxis, susceptibility testing, and management of women with pre-labour
      rupture of membranes. OUTCOMES: Maternal outcomes evaluated included exposure to
      antibiotics in pregnancy and labour and complications related to antibiotic use.
      Neonatal outcomes of rates of early-onset group B streptococcal infections are
      evaluated. EVIDENCE: Published literature was retrieved through searches of
      MEDLINE, CINAHL, and The Cochrane Library from January 1980 to July 2012 using
      appropriate controlled vocabulary and key words (group B streptococcus,
      antibiotic therapy, infection, prevention). Results were restricted to systematic
      reviews, randomized control trials/controlled clinical trials, and observational
      studies. There were no date or language restrictions. Searches were updated on a
      regular basis and incorporated in the guideline to May 2013. Grey (unpublished)
      literature was identified through searching the websites of health technology
      assessment and health technology-related agencies, clinical practice guideline
      collections, clinical trial registries, and national and international medical
      specialty societies. VALUES: The quality of evidence in this document was rated
      using the criteria described in the Report of the Canadian Task Force on
      Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: The recommendations
      in this guideline are designed to help clinicians identify and manage pregnancies
      at risk for neonatal group B streptococcal disease to optimize maternal and
      perinatal outcomes. No cost-benefit analysis is provided. SUMMARY STATEMENT:
      There is good evidence based on randomized control trial data that in women with
      pre-labour rupture of membranes at term who are colonized with group B
      streptococcus, rates of neonatal infection are reduced with induction of labour
      (I). There is no evidence to support safe neonatal outcomes with expectant
      management in this clinical situation. RECOMMENDATIONS: 

PMID- 30103892
TI  - No 298 - Prevention de l'infection neonatale a streptocoques du groupe B
      d'apparition precoce.

PMID- 30103893
TI  - No. 285-Toxoplasmosis in Pregnancy: Prevention, Screening, and Treatment.
AB  - BACKGROUND: One of the major consequences of pregnant women becoming infected by
      Toxoplasma gondii is vertical transmission to the fetus. Although rare,
      congenital toxoplasmosis can cause severe neurological or ocular disease (leading
      to blindness), as well as cardiac and cerebral anomalies. Prenatal care must
      include education about prevention of toxoplasmosis. The low prevalence of the
      disease in the Canadian population and limitations in diagnosis and therapy limit
      the effectiveness of screening strategies. Therefore, routine screening is not
      currently recommended. OBJECTIVE: To review the prevention, diagnosis, and
      management of toxoplasmosis in pregnancy. OUTCOMES: Outcomes evaluated include
      the effect of screening on diagnosis of congenital toxoplasmosis and the efficacy
      of prophylaxis and treatment. EVIDENCE: The Cochrane Library and Medline were
      searched for articles published in English from 1990 to the present related to
      toxoplasmosis and pregnancy. Additional articles were identified through
      references of these articles. VALUES: The quality of evidence is rated and
      recommendations made according to guidelines developed by the Canadian Task Force
      on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: Guideline
      implementation should assist the practitioner in developing an approach to
      screening for and treatment of toxoplasmosis in pregnancy. Patients will benefit
      from appropriate management of this condition. SPONSOR: The Society of
      Obstetricians and Gynaecologists of Canada. RECOMMENDATIONS: 

PMID- 30103894
TI  - No 285 - Toxoplasmose pendant la grossesse : Prevention, depistage et traitement.

PMID- 30103895
TI  - Role of rotavirus vaccination on an emerging G8P[8] rotavirus strain causing an
      outbreak in central Japan.

PMID- 30103896
TI  - Our response to the letter to the editor.

PMID- 30103897
TI  - HAMSCs/HBMSCs coculture system ameliorates osteogenesis and angiogenesis against
      glucolipotoxicity.
AB  - Osteoporosis and vascular lesions induced by glucolipotoxicity are common
      complications of diabetes mellitus (DM). In order to deal with these
      complications, we designed a new therapeutic strategy, i.e. coculture system
      containing human amnion-derived mesenchymal stem cells (HAMSCs) and human bone
      marrow mesenchymal stem cells (HBMSCs). Two in vitro coculture models, transwell
      and mixed cocultures, were proposed for 7 days with variable HAMSCs: HBMSCs
      ratios. Then, supernatant from each coculture was used to reverse the deficiency
      of HBMSCs and human umbilical vein endothelial cells (HUVECs) impaired by high
      glucose and palmitic acid (GP). We found that glucolipotoxicity caused by GP
      remarkably inhibited cell proliferation, osteogenic differentiation and
      superoxide dismutase (SOD) activity, as well as induced the reactive oxygen
      species (ROS) level in HBMSCs. Meanwhile, glucolipotoxicity suppressed cell
      proliferation, tube formation capacity and angiogenic potential of HUVECs.
      Though, HAMSCs/HBMSCs coculture system reduced HBMSCs dysfunction by antioxidant
      properties and promoted angiogenesis in HUVECs. The mixed HAMSCs/HBMSCs coculture
      at the optimal ratio of 3/1 showed significantly greater cell proliferation,
      antioxidant properties, osteogenic and angiogenic differentiation than HBMSCs or
      HUVECs alone. In conclusion, the current coculture system of HAMSCs/HBMSCs can be
      a potential therapeutic material for advancing bone and vascular regeneration
      against DM-induced glucolipotoxicity.

PMID- 30103898
TI  - Glucagon-Like peptide-1: A new therapeutic target to treat abdominal aortic
      aneurysm?
AB  - Recent antidiabetic drugs including GLP-1 receptor agonists and DPP-IV inhibitors
      have demonstrated protective effects in several cardiovascular diseases but their
      effect in abdominal aortic aneurysm (AAA) is far less known. AAA can be
      associated with extremely high rates of mortality and pharmacological treatments
      are still lacking underlining the real need to identify new therapeutic targets.
      The aim of this review was to summarize current knowledge on the role of GLP-1
      pathway in AAA. A systematic literature review was performed and 6 relevant
      studies (2 clinical and 4 experimental) were included. Experimental studies
      demonstrated a protective effect of both GLP-1 receptor agonists and DPP-IV
      inhibitors through targeting the main pathophysiological mechanisms underlying
      AAA formation. The effects of these drugs in human AAA are still poorly known. In
      the limelight of clinical and experimental studies, we discuss current limits and
      future directions.

PMID- 30103899
TI  - In vitro and in silico studies of naphthoquinones and peptidomimetics toward
      Plasmodium falciparum plasmepsin V.
AB  - Plasmodium proteases play both regulatory and effector roles in essential
      biological processes in this important pathogen and have long been investigated
      as drug targets. Plasmepsin V from P. falciparum (PfPMV) is an essential protease
      that processes proteins for export into the host erythrocyte and is a focus of
      ongoing drug development efforts. In the present study, recombinant protein
      production, inhibition assays, binding studies as well as molecular docking and
      molecular dynamics simulation studies were used to investigate the mode of
      binding of a PEXEL-based peptidomimetic and naphthoquinone compounds to PfPMV.
      Consistent with our previous study, refolded PfPMVs were produced with functional
      characteristics similar to the soluble counterpart. Naphthoquinone compounds
      inhibited PfPMV activity by 50% at 50 MUM but did not affect pepsin activity. The
      IC50 values of compounds 31 and 37 against PfPMV were 22.25 and 68.94 MUM,
      respectively. Molecular dynamics simulations revealed that PEXEL peptide
      interacted with PfPMV active site residues via electrostatic interactions while
      naphthoquinone binding preferred van der Waal interactions. P1'-Ser of the PfEMP2
      substrate formed an additional H-bond with Asp365 promoting the catalytic
      efficiency. Additionally, the effect of metal ions on the secondary structure of
      PfPMV was examined. Our results confirmed that Hg2+ ions reversibly induced the
      changes in secondary structure of the protein whereas Fe3+ ions induced
      irreversibly. No change was observed in the presence of Ca2+ ions. Overall, the
      results here suggested that naphthoquinone derivatives may represent another
      source of antimalarial inhibitors targeting aspartic proteases but further
      chemical modifications are required.

PMID- 30103900
TI  - FasL on the surface of Tag7 (PGRP-S)-activated lymphocytes induces necroptosis in
      HLA-negative tumor cells with the involvement of lysosomes and mitochondria.
AB  - Recently we have found that cytokine IL-2 and innate immunity protein Tag7
      activate cytotoxic lymphocytes that kill HLA-negative tumor cells, inducing both
      apoptosis and necroptosis. Here we decrypt the processes, taking part in
      necroptosis execution after FasL-Fas interaction. Necroptosis begins with RIPK1
      activation and necrosome formation. Subsequent activation of MLKL results in the
      increase of Ca2+ level in the cell and activation of Ca2+-dependent enzymes
      causing lysosomal membrane permeabilization and the release of cathepsins to the
      cytosol. STAT3 translocation to the mitochondria and binding to a component of
      the respiratory chain complex I causes ROS accumulation. We have shown that
      transduction of necroptotic signal via TNFR1 and Fas has many common points. It
      is known that apoptosis plays a major role in physiological cell death; however,
      under pathological conditions necroptosis is very common. That is why the
      detailed mechanisms of FasL-Fas necroptosis can help in understanding the
      processes of elimination of tumor cells that have blocked apoptosis signal
      transduction.

PMID- 30103902
TI  - PTSD in civilian populations after hospitalization following traumatic injury: A
      comprehensive review.
AB  - BACKGROUND: Injuries and their comorbidities affect victims far beyond their
      physical recovery period. Some study-measures show that more than half of
      patients hospitalized for a traumatic injury suffer from Acute Stress Disorder,
      alcohol dependence, and recurrent trauma. Overall, this literature review serves
      to review risk factors for PTSD, screening tools, follow-up strategies, and gaps
      in the literature for achieving feasible patient-centered interventions for the
      prevention of PTSD after a traumatic injury. DATA SOURCES: A literature review
      was performed from August 1, 2017 to March 19, 2018, from 3 Databases: PubMed,
      CINAHL and Cochrane, with keywords: "PTSD", "Post-traumatic Stress Disorder",
      "Civilians", "Traumatic", "Injury", "Follow-up", "Treatment", "Referral",
      "surgery", "surgical", "Intervention", and "Insured", "underinsured".
      CONCLUSIONS: Reported risk factors for PTSD were: prior psychiatric disorder,
      gunshots, and lack of social support. Most articles use the Posttraumatic Stress
      Disorder Checklist - Civilian version. Follow-up strategies mainly focus on
      multidisciplinary intervention protocols, including social workers, behavioral
      health specialists, and psychiatrists. Finally, gaps in the literature show the
      need for bilingual/bicultural patient-centered care for elderly, diverse ethnic
      backgrounds, and insured vs. uninsured patients.

PMID- 30103901
TI  - Molecular correlates of intermediate- and high-risk localized prostate cancer.
AB  - Clinicopathologic parameters, including Gleason score, remain the most validated
      prognostic factors for patients diagnosed with localized prostate cancer (PCa).
      However, patients of the same risk groups have exhibited heterogeneity of disease
      outcomes. To improve risk classification, multiple molecular risk classifiers
      have been developed, which were designed to inform beyond existing
      clinicopathologic classifiers. Alterations affecting tumor suppressors and
      oncogenes, such as PTEN, MYC, BRCA2, and TP53, which have been long associated
      with aggressive PCa, demonstrated grade-dependent frequency of alterations in
      localized PCas. In addition to these genetic hallmarks, several RNA-based
      commercial tests have been recently developed to help identify men who would
      benefit from earlier interventions. Large genomic studies also correlate germline
      genetic alterations and epigenetic features with adverse outcomes, further
      strengthening the link between the risk of metastasis and a stepwise accumulation
      of driver molecular lesions.

PMID- 30103903
TI  - Adjuvant transarterial chemoembolization for patients with hepatocellular
      carcinoma involving microvascular invasion.
AB  - BACKGROUND: Microvascular invasion (MVI) has recently been reported to be an
      independent prognostic factor in patients with hepatocellular carcinoma (HCC).
      This study compared the outcomes of adjuvant transarterial chemoembolization (A
      TACE) after hepatic resection (HR) in patients with HCC involving MVI. METHODS:
      This prospective study involved 200 consecutive patients with MVI-HCC who
      underwent HR alone (n = 109) or HR with A-TACE (n = 91).The Kaplan-Meier method
      was used to compare disease-free survival (DFS) and overall survival (OS).
      RESULTS: The two groups showed similar DFS at 1, 2, and 3 years (P = 0.077). The
      A-TACE group showed significantly higher OS than the HR-only group (P = 0.030).
      Subgroup analysis showed that A-TACE was associated with significantly higher DFS
      and OS among patients with a tumor diameter >5 cm or with multinodular tumors.
      CONCLUSIONS: A-TACE may improve postoperative outcomes for MVI-HCC patients,
      especially those with tumor diameter >5 cm or multinodular tumors.

PMID- 30103905
TI  - Multiscale movement coordination dynamics in collaborative team problem solving.
AB  - During collaborative problem solving (CPS), coordination occurs at different
      spatial and temporal scales. This multiscale coordination should play a
      functional role in facilitating effective collaboration. To evaluate this, we
      conducted a study of computer-based CPS with 42 dyadic teams. We used cross
      wavelet coherence to examine movement coordination, extracted from videos, at
      several scales, and tested whether the observed coordination was greater than
      expected due to chance and due to task demands. We found that coordination at
      scales less than 2s was greater than chance and at most scales (except 16s, 1m,
      and 2m), was greater than expected due to task demands. Lastly, we observed that
      coherence at .25s and 1s scales was predictive of performance. However, when
      including relative phase, our results suggest that higher in-phase movement
      coordination at the 1s scale was the strongest predictor of CPS performance.
      Further, we used growth curve modeling to examine how movement coordination
      changes across the duration of the task and whether this is moderated by CPS
      performance. We found that coordination over the duration of the CPS task is
      quadratic (a U shape) and that better performing teams have higher coordination
      with a shallower curve. We discuss these findings and their relevance to
      understanding how low-level movement coordination facilitates CPS.

PMID- 30103904
TI  - [5-fluorouracil therapeutic drug monitoring: Update and recommendations of the
      STP-PT group of the SFPT and the GPCO-Unicancer].
AB  - Despite being 60-years old now, 5-FU remains the backbone of numerous regimen to
      treat a variety of solid tumors such as breast, head-and-neck and digestive
      cancers either in neo-adjuvant, adjuvant or metastatic settings. Standard 5-FU
      usually claims 15-40% of severe toxicities and up to 1% of toxic-death. Numerous
      studies show a stiff relationship between 5-FU exposure and toxicity or efficacy.
      In addition, 5-FU pharmacokinetics is highly variable between patients. Indeed,
      80% of the 5-FU dose is catabolized in the liver by dihydropyrimidine
      dehydrogenase (DPD) into inactive compounds. It is now well established that DPD
      deficiency could lead to severe toxicities and, thus, require dose reduction in
      deficient patients. However, despite dosage adaptation based on DPD status, some
      patients may still experience under- or over-exposure, leading to inefficacy or
      major toxicity. The "Suivi therapeutique pharmacologique et personnalisation des
      traitements" (STP-PT) group of the "Societe francaise de pharmacologie et de
      therapeutique" (SFPT) and the "Groupe de pharmacologie clinique oncologique"
      (GPCO)-Unicancer, based on the latest and most up-to-date literature data,
      recommend the implementation of 5-FU Therapeutic Drug Monitoring in order to
      ensure an adequate 5-FU exposure.

PMID- 30103906
TI  - Effect of Atrial Fibrillation and Mitral Valve Gradients on Response to
      Percutaneous Mitral Valve Repair With the MitraClip System.
AB  - Both pre-existing atrial fibrillation (AF) and mitral valve pressure gradients
      (MVPG) created by MitraClip implantation have demonstrated predictive power for
      unfavorable outcomes. Therefore, we aimed to assess the impact of MVPG following
      MitraClip on outcomes in patients with and without AF. A total of 200 patients
      who underwent MitraClip implantation in our institution were enrolled.
      Echocardiography was obtained before and after the procedure. The primary
      endpoint of the study was all-cause mortality 1-year after MitraClip
      implantation. Secondary end points were clinical improvements in NYHA functional
      class and reduction in MR severity after MitraClip implantation. Two hundred
      patients (74 +/- 10 years, left ventricular ejection fraction 41% +/- 14%,
      logistic EuroSCORE I 21 +/- 15) were enrolled into the final analysis. One
      hundred twelve patients (56%) had pre-existing AF. One-year all-cause mortality
      was 17% without any differences between patients with or without pre-existing AF.
      Comparing postprocedural MVPG of surviving and deceased patients, deceased
      patients with pre-existing AF exhibited significantly elevated postprocedural
      MVPG compared with surviving patients without AF (4.8 +/- 2.1 mm Hg vs 3.6 +/-
      1.8 mm Hg; p = 0.010). ROC analysis and Kaplan-Meier survival curves identified
      significantly reduced survival in AF patients with postprocedural MVPG above 4.0
      mm Hg (p = 0.011). After MitraClip, a MVPG above 4.0 mm Hg in patients with pre
      existing AF was a significant outcome predictor in univariate and multivariate
      analysis. In conclusion, we identified a high-risk cohort characterized by
      postprocedural MVPG above 4.0 mm Hg and pre-existing AF predicting poor long-term
      outcome.

PMID- 30103907
TI  - Spatial working memory in Progressive Supranuclear Palsy.
AB  - The neural and cognitive mechanisms of spatial working memory are tightly coupled
      with the systems that control eye-movements but the precise nature of this
      coupling is not well understood. In particular, there are very few
      neuropsychological studies that explicitly examine how deficits of oculomotor
      control affect visuospatial working memory. Here, we examined the link between
      spatial working memory and the oculomotor system in a sample of patients with
      Progressive Supranuclear Palsy, a degenerative neurological disease characterised
      by defective vertical eye-movements but relatively preserved horizontal eye
      movements. Consistent with the idea that the oculomotor system plays a critical
      role in spatial working memory performance, people with PSP had significantly
      shorter spatial spans when stimuli were presented along the vertical axis
      compared to the horizontal axis. This effect was not observed in age matched
      controls. We hypothesise that PSP disrupts a colliculo-parietal feedback loop
      that contributes to the maintenance of activation in a parietal priority map
      during the delay period. This result is the first direct neuropsychological
      evidence for an association between oculomotor function and spatial working
      memory and is broadly consistent with idea that rehearsal in visuospatial working
      memory is mediated by an 'oculomotor loop', as proposed by Baddeley (1986). We
      conclude that optimal spatial working memory performance depends on an intact
      oculomotor system.

PMID- 30103909
TI  - A review of treatment options for behavioural manifestations of clinical anxiety
      as a comorbidity in dogs with idiopathic epilepsy.
AB  - Psychiatric comorbidities affect a large percentage of people with epilepsy and
      have a detrimental impact on their quality of life. Recently, behavioural
      comorbidities, with similar characteristics to human psychiatric diseases, have
      been identified in dogs with idiopathic epilepsy. In particular, behaviours
      motivated by the fear-anxiety emotional system have been found to be associated
      with the occurrence of idiopathic epilepsy in both dogs receiving anti-epileptic
      drugs, and drug-naive dogs. There has been little research into the relationship
      between epilepsy and behavioural signs, and even less into potential treatment
      protocols. The following article will review available literature from human
      medicine to describe the current state of knowledge about the bi-directional
      relationship between anxiety and epilepsy, draw parallels from reported
      anxiogenic and anxiolytic properties of anti-epileptic drugs and attempt to
      provide pharmaceutical and behavioural guidance for veterinary patients with
      epilepsy and comorbid anxiety.

PMID- 30103908
TI  - Diffusion of Ca2+ from Small Boutons en Passant into the Axon Shapes AP-Evoked
      Ca2+ Transients.
AB  - Not only the amplitude but also the time course of a presynaptic Ca2+ transient
      determine multiple aspects of synaptic transmission. In small bouton-type
      synapses, the mechanisms underlying the Ca2+ decay kinetics have not been fully
      investigated. Here, factors that shape an action-potential-evoked Ca2+ transient
      were quantitatively studied in synaptic boutons of neocortical layer 5 pyramidal
      neurons. Ca2+ transients were measured with different concentrations of
      fluorescent Ca2+ indicators and analyzed based on a single-compartment model. We
      found a small endogenous Ca2+-binding ratio (7 +/- 2) and a high activity of Ca2+
      transporters (0.64 +/- 0.03 ms-1), both of which enable rapid clearance of Ca2+
      from the boutons. However, contrary to predictions of the single-compartment
      model, the decay time course of the measured Ca2+ transients was biexponential
      and became prolonged during repetitive stimulation. Measurements of [Ca2+]i along
      the adjoining axon, together with an experimentally constrained model, showed
      that the initial fast decay of the Ca2+ transients predominantly arose from the
      diffusion of Ca2+ from the boutons into the axon. Therefore, for small boutons en
      passant, factors like terminal volume, axon diameter, and the concentration of
      mobile Ca2+-binding molecules are critical determinants of Ca2+ dynamics and thus
      Ca2+-dependent processes, including short-term synaptic plasticity.

PMID- 30103910
TI  - Evaluation of a portable ion-selective electrode meter for measuring potassium
      concentrations in whole blood and plasma of calves.
AB  - An ion-selective electrode (ISE) handheld meter (LAQUAtwin B-731; Horiba) has
      recently become available for the measurement of potassium concentrations [K+] in
      biological fluids. The ISE meter has the potential to facilitate the diagnosis
      and treatment of potassium balance disorders of critically ill cattle. The
      objective of this study was to characterise the analytical performance of the ISE
      meter in a study sample of hospitalised calves with a broad range of plasma [K+].
      For the purpose of the study, whole blood and plasma samples from 125 calves
      (age<=3months) were used for analysis. The accuracy of the meter against the
      reference method (indirect ISE, Cobas c 311, Roche) was assessed using Passing
      Bablok regression and Bland-Altman plots. The [K+] in whole blood as measured by
      the ISE meter in direct mode ranged from 2.4 to 9.9mmol/L. The meter measured
      whole blood [K+] as 3.8% higher than plasma [K+]. Passing-Bablok regression for
      whole blood [K+] measured by the meter against plasma [K+] determined by indirect
      potentiometry revealed a linear relationship that was almost identical to the
      line of identity. However, the Bland-Altman plot indicated that the meter
      measured plasma [K+] 5.1% lower than the reference method. This result was
      consistent with analytical differences of direct and indirect ISE methods in
      respect to variation in the plasma protein concentration. In conclusion, the
      LAQUAtwin B-731 meter provides an accurate, rapid and low-cost tool for the
      diagnosis of potassium derangements in critically ill calves, particularly when
      whole blood samples are analysed.

PMID- 30103911
TI  - Bayesian latent class estimation of sensitivity and specificity parameters of
      diagnostic tests for bovine tuberculosis in chronically infected herds in
      Northern Ireland.
AB  - In the European Union, the recommended ante-mortem diagnostic methods for bovine
      tuberculosis (bTB) include the single intradermal cervical comparative tuberculin
      (SICCT) test and the interferon-gamma (IFN-gamma) test as an ancillary test. The
      SICCT test has a moderate sensitivity (Se) and high specificity (Sp), while the
      IFN-gamma test has good Se, but a lower Sp than the SICCT test. A retrospective
      Bayesian latent class analysis was conducted on 71,185 cattle from 806 herds
      chronically infected with bTB distributed across Northern Ireland (NI) to
      estimate the Se and Sp of the common ante-mortem tests and meat inspection.
      Analyses were also performed on data stratified by farming type and herd location
      to explore possible differences in test performance given the heterogeneity in
      the population. The mean estimates in chronically infected herds were: (1)
      'standard' SICCT: Se 40.5-57.7%, Sp 96.3-99.7%; (2) 'severe' SICCT: Se 49.0%
      60.6%, Sp 94.4-99.4%; (3) IFN-gamma(bovine-avian) using a NI optical density (OD)
      cut-off difference of 0.05: IFN-gamma(B-A)NI: Se 85.8-93.0%, Sp 75.6-96.2%; (4)
      IFN-gamma(bovine-avian) using a standard 'commercial' OD cut-off difference of
      0.1: IFN-gamma(B-A)0.1: Se 83.1-92.1%, Sp 83.1-97.3%; and (5) meat inspection: Se
      49.0-57.1% Se, Sp 99.1-100%. Se estimates were lower in cattle from dairy farms
      than from beef farms. There were no notable differences in estimates by location
      of herds. Certain population characteristics, such as production type, might
      influence the ability of bTB tests to disclose truly infected cases.

PMID- 30103912
TI  - Investigation of the treatment of sand accumulations in the equine large colon
      with psyllium and magnesium sulphate.
AB  - Enteropathy associated with sand accumulation in the large colon of horses has
      been reported worldwide. Intestinal sand accumulations are commonly treated
      medically, but randomised controlled clinical trials on horses are scarce. This
      prospective study evaluated the efficacy of an enterally administered combination
      of psyllium and magnesium sulphate (MgSO4) for the removal of large colonic sand
      accumulations in horses without clinical signs of acute colic. The two groups
      comprised 20 untreated control horses and 20 horses treated with 1g/kg bodyweight
      (bwt) of psyllium and 1g/kg bwt of MgSO4 administered by nasogastric intubation
      once daily for 4 days. Both groups had no access to soil during the study period.
      The amounts of accumulated sand were evaluated radiographically before and after
      treatment. Significantly more treated horses cleared their sand accumulations
      than horses in the control group. This clearance was determined by observing the
      estimated quantity by area of sand remaining in the large colon (P<0.001) and by
      comparing the numbers of successfully treated horses (P=0.004) between the two
      groups after 4days of treatment. However, there were unexplained individual
      variations in the clearance of sand accumulation.

PMID- 30103913
TI  - Regional anesthetic techniques for the pelvic limb and abdominal wall in small
      animals: A review of the literature and technique description.
AB  - Increasing interest in using peripheral nerve blocks in small animals is evident,
      given the numerous studies published recently on this topic in important
      veterinary journals. Initially, research was focused on intraoperative analgesia
      to the pelvic limb, and several descriptions of lumbosacral plexus, femoral and
      sciatic nerve blocks have been described in studies. There is recent interest in
      developing techniques for somatosensory blockade of the abdominal wall. This
      article is the second part of a two-part review of regional anesthesia (RA) in
      small animals, and its aim is to discuss the most relevant studies in the
      veterinary literature, where objective methods of nerve location have been used,
      and to illustrate in pictures the currently used techniques for providing RA to
      the abdominal wall and the pelvic limb in small animals.

PMID- 30103914
TI  - Use of statistical modelling to investigate the pathogenesis of claw horn
      disruption lesions in dairy cattle.
AB  - Claw horn disruption lesions (CHDLs) in dairy cattle account for a large
      proportion of lameness. The aim of this review is to provide an update on the
      evidence surrounding the pathogenesis of CHDLs, in the context of how statistical
      modelling has contributed to the validity of available evidence and current
      thinking. Historically, 'subclinical laminitis' has often been used to describe
      the commonly accepted underlying pathology associated with these lesions, however
      progress in understanding the aetiopathogenesis of CHDLs and a lack of clear
      evidence to support the traditional laminitis hypothesis, means use of this
      terminology has been challenged. With advancements in statistical modelling
      capabilities within the veterinary field, the multifactorial and complex nature
      of CHDLs can be more fully explored. This has led to an increased understanding
      of environmental and animal-based risk factors and their role in the pathogenesis
      of CHDLs, as well as highlighting future research areas. There is still a need
      for further research using intervention studies to demonstrate causality for
      identified risk factors to date, as well as quantifying the impact of these risk
      factors at the population level. Some important considerations when using and
      interpreting statistical models in lameness research are discussed with a
      critical assessment of the key statistical issues in published research
      investigating the pathogenesis of CHDLs.

PMID- 30103915
TI  - Practical considerations for clinical use of mesenchymal stem cells: From the
      laboratory to the horse.
AB  - Since the clinical use of mesenchymal stem cells (MSCs) for treating
      musculoskeletal injuries is gaining popularity, practitioners should be aware of
      the factors that may affect MSCs from tissue harvesting for MSC isolation to cell
      delivery into the injury site. This review provides equine practitioners with up
      to-date, practical knowledge for the treatment of equine patients using MSCs. A
      brief overview of laboratory procedures affecting MSCs is provided, but the main
      focus is on shipping conditions, routes of administration, injection methods, and
      which commonly used products can be combined with MSCs and which products should
      be avoided as they have deleterious effects on cells. There are still several
      knowledge gaps regarding MSC-based therapies in horses. Therefore, it is
      important to properly manage the factors which are currently known to affect
      MSCs, to further strengthen the evidence basis of this treatment.

PMID- 30103916
TI  - Circannual variability in adrenocorticotropic hormone responses to administration
      of thyrotropin-releasing hormone in clinically normal horses in Australia.
AB  - Thyrotropin releasing hormone (TRH)-stimulation testing for pituitary pars
      intermedia dysfunction (PPID) in horses is only recommended at certain times of
      the year. Current diagnostic cut-off values reflect testing in the northern
      hemisphere during this time. The aims of this study were to evaluate TRH
      stimulation testing during two different phases of the circannual pituitary cycle
      and to determine whether diagnostic cut-off values developed in the northern
      hemisphere are appropriate in Australia. Thirteen clinically normal horses at
      Perth, Western Australia, and 23 horses at Townsville, Queensland, Australia, had
      TRH stimulation tests performed at two different time points during the
      circannual pituitary cycle. At both locations, post-TRH adrenocorticotropic
      hormone (ACTH) concentrations were significantly different between testing time
      points (Perth: P=0.001; Townsville: P<0.0001). In Perth, the mean ACTH
      concentrations 10min post-TRH in September and March were 51.4pg/mL (95%
      confidence interval, CI, 46.4-56.4pg/mL) and 248.5pg/mL (95% CI 170.2
      326.9pg/mL), respectively. The median percentage change in ACTH concentrations in
      March was 361.9%. In Townsville, the mean ACTH concentrations 30min post-TRH in
      September and April were 35.3pg/mL (95% CI 29.6-40.9pg/mL) and 112.3pg/mL (95% CI
      93.4-131.2pg/mL), respectively. The median percentage change in ACTH
      concentrations in April was 144.7%. The ACTH cut-off value after TRH stimulation
      in normal horses in September in Perth and Townsville was similar to the values
      established in the northern hemisphere. However, TRH stimulation testing in
      March/April was highly variable at both locations.

PMID- 30103917
TI  - Cardiopulmonary effects of vatinoxan in sevoflurane-anaesthetised sheep receiving
      dexmedetomidine.
AB  - The effects of pre-treatment with vatinoxan (MK-467) on dexmedetomidine-induced
      cardiopulmonary alterations were investigated in sheep. In a crossover study
      design with a 20-day washout, seven sheep were anaesthetised with sevoflurane in
      oxygen and air. The sheep were ventilated with the pressure-limited volume
      controlled mode and a positive end-expiratory pressure of 5cmH2O. Peak
      inspiratory pressure (PIP) was set at 25cmH2O. The sheep received either
      150MUg/kg vatinoxan HCl (VAT+DEX) or saline intravenously (IV) 10min before IV
      dexmedetomidine HCl (3MUg/kg, DEX). Cardiopulmonary variables were measured
      before treatments (baseline), 3min after vatinoxan or saline, and 5, 15 and 25min
      after dexmedetomidine. Computed tomography (CT) of lung parenchyma was performed
      at baseline, 2min before dexmedetomidine, and 10, 20 and 30min after DEX.
      Bronchoalveolar lavage (BAL) was performed after the last CT scan and shortly
      before sheep recovered from anaesthesia. After VAT, cardiac output significantly
      increased from baseline. DEX alone significantly decreased partial arterial
      oxygen tension, total dynamic compliance and tidal volume, whereas PIP was
      significantly increased. With VAT+DEX, these changes were minimal. No significant
      changes were detected in haemodynamics from baseline after DEX. With VAT+DEX,
      mean arterial pressure and systemic vascular resistance were significantly
      decreased from baseline, although hypotension was not detected. On CT, lung
      density was significantly increased with DEX as compared to baseline. No visual
      abnormalities were detected in bronchoscopy and no differences were detected in
      the BAL fluid after either treatment. The pre-administration of vatinoxan
      alleviates dexmedetomidine-induced bronchoconstriction, oedema and hypoxaemia in
      sevoflurane-anaesthetised sheep.

PMID- 30103919
TI  - Differentiating the biological effects of linoleic acid from arachidonic acid in
      health and disease.
AB  - Dietary fatty acids are associated with the development of many chronic diseases,
      such as obesity, diabetes, cardiovascular disease, metabolic syndrome, and
      several cancers. This review explores the literature surrounding the combined and
      individual roles of n-6 PUFAs linoleic acid (LA) and arachidonic acid (AA) as
      they relate to immune and inflammatory response, cardiovascular health, liver
      health, and cancer. The evidence suggests that a pro-inflammatory view of LA and
      AA may be over simplified. Overall, this review highlights gaps in our
      understanding of the biological roles of LA, AA and their complex relationship
      with n-3 PUFA and the need for future studies that examine the roles of
      individual fatty acids, rather than groups.

PMID- 30103918
TI  - Constant rate infusion vs. intermittent bolus administration of IV furosemide in
      100 pets with acute left-sided congestive heart failure: A retrospective study.
AB  - The aim of this study was to determine whether the addition of constant rate
      infusion (CRI) to intermittent intravenous bolus (IVB) administration of
      furosemide resulted in an improvement in medical outcomes in dogs and cats with
      acute left-sided congestive heart failure (L-CHF). A total of 76 client-owned
      dogs and 24 client-owned cats admitted with acute L-CHF were retrospectively
      divided between an IVB group (43 dogs and 16 cats) and a CRI group (33 dogs and 8
      cats). The median furosemide dose used in dogs in the CRI group (median
      0.99mg/kg/h; range 0.025-3.73mg/kg/h) was lower than the dose used in dogs in the
      IVB group (median 1.19mg/kg/h; range 0.027-7.14mg/kg/h; P=0.008). Respiratory
      rates were lower in the IVB group (P=0.005) and the CRI group (P=0.039) compared
      to pre-treatment values. The overall short-term mortality was 15%. A trend of
      longer hospitalisation in the IVB group relative to the CRI group (P=0.07) was
      shown. Creatinine and total plasma protein concentrations increased more in the
      CRI group than in the IVB group, suggestive of a higher risk of dehydration and
      azotaemia. There may be safety profile differences between CRI and IVB,
      warranting a prospective study using a larger sample size.

PMID- 30103921
TI  - Fatty acid composition of breast milk in Galicia (NW Spain): A cross-country
      comparison.
AB  - Based on the premise that the fatty acid composition of human milk can be
      substantially altered by diet, the current study investigated the fatty acid
      profile (fattyacidome) of breast milk in Galicia, a small region located in the
      north-west of Spain and characterized by the Southern European Atlantic Diet
      (SEAD). A cross-country comparison was also performed to assess worldwide variety
      and diet impact, reviewing the profiles reported various European, North and
      South American, Asian and African countries and Australia. Galician human milk
      appeared similar to the rest of Europe, with some particular features related to
      the SEAD (dairy, pork, beef and sunflower and olive oils), such as relatively
      high levels of linoleic acid and lower alpha-linolenic acid. The results also
      showed the existence of woman-specific profiles and significant changes over
      lactation in some fatty acids. Worldwide, the fatty acid profiles were similar,
      with the clear exception of Asiatic breast milk. The impact of fatty acids on
      infant health warrants further investigation.

PMID- 30103922
TI  - F2-isoprostanes and fatty acids profile in early pregnancy complicated by pre
      existing diabetes.
AB  - BACKGROUND: Diabetes and pregnancy are both associated with oxidative stress,
      characterized by an increase of F2-isoprostanes from the non-enzymatic oxidation
      of arachidonic acid, a n - 6 polyunsaturated fatty acid (PUFA). We hypothesized
      that pregnant women with pre-existing diabetes will be characterized by elevated
      levels of specific F2-isoPs isomers and altered PUFA composition in plasma early
      pregnancy when compared to normoglycemic controls. METHODS: Plasma samples from
      23 women with uncomplicated pregnancies and 11 women with pre-existing diabetes
      in pregnancy were collected between 12 and 18 weeks of pregnancy (MIROS cohort).
      Six F2-isoprostanes isomers were measured by high-performance liquid
      chromatography coupled to tandem mass spectrometry. Fatty acids concentrations in
      plasmatic phospholipids were measured by gas chromatography coupled to a flame
      ionization detector. RESULTS: F2-isoprostanes, specifically the 8-iso-15(R)
      PGF2alpha levels, were 67% higher in diabetic than normoglycemic pregnancies (p =
      0.026). The total n - 6 PUFA and arachidonic acid level did not differ between
      study groups. In contrast, total n - 3 level was 32% lower in diabetic
      pregnancies than in controls (p = 0.002); EPA(20:5) and DHA(22:6) being
      specifically reduced (p = 0.035 and p = 0.003 respectively). Delta-6-desaturase
      (D6D) activity index, calculated using fatty acid ratios, was 9% lower in pre
      existing diabetes than in controls (p = 0.042). CONCLUSIONS: Pre-existing
      diabetes in early pregnancy displays a distinctive F2-isoprostanes profile when
      compared to other pathologies of pregnancy, such as preeclampsia, as previously
      assessed in the same cohort.

PMID- 30103920
TI  - Bm-iAANAT and its potential role in fatty acid amide biosynthesis in Bombyx mori.
AB  - The purpose of this research is to unravel the substrate specificity and kinetic
      properties of an insect arylalkylamine N-acyltransferase from Bombyx mori (Bm
      iAANAT) and to determine if this enzyme will catalyze the formation of long chain
      N-acylarylalkylamides in vitro. However, the determination of substrates and
      products for Bm-iAANAT in vitro is no guarantee that these same molecules are
      substrates and products for the enzyme in the organism. Therefore, RT-PCR was
      performed to detect the Bm-iAANAT transcripts and liquid chromatography
      quadrupole time-of-flight mass spectrometry (LC-QToF-MS) analysis was performed
      on purified lipid extracts from B. mori larvae (fourth instar, Bmi4) to determine
      if long chain fatty acid amides are produced in B. mori. Ultimately, we found
      that recombinant Bm-iAANAT will utilize long-chain acyl-CoA thioesters as
      substrates and identified Bm-iAANAT transcripts and long-chain fatty acid amides
      in Bmi4. Together, these data show Bm-iAANAT will catalyze the formation of long
      chain N-acylarylalkylamides in vitro and provide evidence demonstrating that Bm
      iAANAT has a role in fatty acid amide biosynthesis in B. mori, as well.

PMID- 30103923
TI  - Dietary caprylic acid and ghrelin O-acyltransferase activity to modulate
      octanoylated ghrelin functions: What is new in this nutritional field?
AB  - Caprylic acid (octanoic acid, C8:0) belongs to the class of medium-chain
      saturated fatty acids (MCFAs). Dairy products and specific oils such as coconut
      oil are natural sources of dietary caprylic acid. MCFAs display distinct chemico
      physical and metabolic properties from those of long-chain saturated fatty acids
      (LCFAs >= 12 carbons) and potential beneficial physiological effects of dietary
      C8:0 have been studied for many years. More recently, caprylic acid was shown to
      octanoylate ghrelin, the only known peptide hormone with an orexigenic effect.
      Through its covalent binding to the ghrelin peptide, caprylic acid exhibits an
      emerging and specific role in modulating physiological functions themselves
      regulated by octanoylated ghrelin. Dietary caprylic acid is therefore now
      suspected to provide the ghrelin O-acyltransferase (GOAT) enzyme with octanoyl
      CoA co-substrates necessary for the acyl modification of ghrelin. Recent studies
      suggest that decreasing the circulating octanoylated ghrelin level through the
      inhibition of GOAT activity, or simply by modulating the availability of its C8:0
      substrate, might constitute a therapeutic strategy against obesity. Both dietary
      caprylic acid availability and GOAT activity may indeed be important to modulate
      octanoylated ghrelin concentration and functions. This review highlights recent
      findings in the field of nutrition.

PMID- 30103924
TI  - Concentrations of oxidized linoleic acid derived lipid mediators in the amygdala
      and periaqueductal grey are reduced in a mouse model of chronic inflammatory
      pain.
AB  - Chronic pain is both a global public health concern and a serious source of
      personal suffering for which current treatments have limited efficacy. Recently,
      oxylipins derived from linoleic acid (LA), the most abundantly consumed
      polyunsaturated fatty acid in the modern diet, have been implicated as mediators
      of pain in the periphery and spinal cord. However, oxidized linoleic acid derived
      mediators (OXLAMs) remain understudied in the brain, particularly during pain
      states. In this study, we employed a mouse model of chronic inflammatory pain
      followed by a targeted lipidomic analysis of the animals' amygdala and
      periaqueductal grey (PAG) using LC-MS/MS to investigate the effect of chronic
      inflammatory pain on oxylipin concentrations in these two brain nuclei known to
      participate in pain sensation and perception. From punch biopsies of these brain
      nuclei, we detected twelve OXLAMs in both the PAG and amygdala and one
      arachidonic acid derived mediator, 15-HETE, in the amygdala only. In the
      amygdala, we observed an overall decrease in the concentration of the majority of
      OXLAMs detected, while in the PAG the concentrations of only the epoxide LA
      derived mediators, 9,10-EpOME and 12,13-EpOME, and one trihydroxy LA derived
      mediator, 9,10,11-TriHOME, were reduced. This data provides the first evidence
      that OXLAM concentrations in the brain are affected by chronic pain, suggesting
      that OXLAMs may be relevant to pain signaling and adaptation to chronic pain in
      pain circuits in the brain and that the current view of OXLAMs in nociception
      derived from studies in the periphery is incomplete.

PMID- 30103925
TI  - Stearidonic acid combined with alpha-linolenic acid improves lipemic and
      neurological markers in a rat model subject to a hypercaloric diet.
AB  - In this study, we hypothesized that terrestrial plant oils, rich in alpha
      linolenic acid (ALA) and stearidonic acid (SDA) relative to fish oil, rich in
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent negative
      effects on cardiovascular and neurological function using a rat model fed a
      hypercaloric diet. Results showed effects on the FA profile, namely,
      eicosapentaenoic, EPA, and docosahexaenoic, DHA, levels. There were also effects
      on neural aspects (cAMP response element-binding protein, CREB, gene expression,
      at least, doubled) and the pro-inflammatory/anti-inflammatory balance (TNF-alpha,
      tumor necrosis factor alpha reduced by 30-50%). The most positive impact of ALA
      and SDA was the beneficial reduction of total lipids (from 395 +/- 3 to 352-361
      mg/dL), VLDL-cholesterol (from 21.8 +/- 0.2 to 14.1-17.8 mg/dL), and
      triacylglycerols (from 109 +/- 1 to 71-89 mg/dL) in both LIN (diet enriched in
      linseed oil) and BUG (diet enriched in Buglossoides oil) groups. Overall, data
      indicate that ALA- and SDA-rich lipid sources may counteract the undesirable
      cardiovascular effects of a hypercaloric diet based on milk fat.

PMID- 30103927
TI  - Why docosapentaenoic acid is not included in the Omega-3 Index.
AB  - As currently defined, the Omega-3 Index comprises eicosapentaenoic acid (EPA) and
      docosahexaenoic acid (DHA), but not docosapentaenoic acid (DPA) in erythrocytes.
      In fish and many fish oils DPA is detectable (along with EPA and DHA), but
      sources rich in DPA are scarce. Purified DPA is available, and DPA is a precursor
      of biologically active molecules, but much remains to be learned about the
      effects of DPA in humans. In epidemiologic studies, erythrocyte DPA did not
      predict risk for total mortality, sudden cardiac death, or other relevant
      cardiovascular events, and, more importantly, did not improve prediction of these
      events when included along with EPA and DHA, the original Omega-3 Index. We
      conclude that current scientific evidence does not support including DPA into the
      Omega-3 Index.

PMID- 30103928
TI  - 15-Lipoxygenase/15-hydroxyeicosanoid and activator protein 1 contribute to
      hypoxia-induced pulmonary artery smooth muscle cells phenotype alteration.
AB  - We have previously shown that 15-lipoxygenase (15-LOX) and its metabolite 15
      hydroxyeicosanoid (15-HETE) play a critical role on hypoxia-triggered pulmonary
      artery smooth muscle cell (PASMC) phenotype alteration through multifactorial
      pathways, like extracellular signal-regulated kinase and p38 mitogen-activated
      protein kinases. Here, we hypothesize that activator protein 1 (AP-1) was also
      involved in the PASMC phenotype alteration. Hypoxia elevated AP-1 expression in
      pulmonary arterials and in cultured PASMCs with a time-dependent manner. Both the
      gene disruption and pharmacological inactivation of 15-lipoxygenase (15-LOX)
      significantly attenuated the hypoxia-elevated AP-1 expression. Silencing of AP-1
      with small interference RNA abrogated the hypoxia- and 15-HETE-increased cell
      viability, proliferating cell nuclear antigen expression, and Ki67 and alpha
      tubulin staining. Moreover, AP-1 knockdown prevented hypoxia- and 15-HETE
      promoted cyclin D1 expression and subsequent cell cycle progression into G2/M+S
      phase. Interestingly, AP-1 knockdown also inhibited the expression of 15-LOX,
      indicating a feedback regulation of 15-LOX/15-HETE signaling by AP-1. These
      findings shed light on the involvement of AP-1 in the PASMCs phenotype alteration
      via the hypoxia/15-LOX/15-HETE signaling.

PMID- 30103929
TI  - Intra-individual variability of long-chain fatty acids (C12-C24) in plasma and
      red blood cells.
AB  - Long-chain fatty acids (LCFA) play key roles in mammalian cells as sources of
      energy, structural components and signaling molecules. Given their importance in
      numerous physiological processes, the roles of LCFAs in health and disease have
      been extensively investigated. In the majority of studies, correlations are
      established using a single measurement in plasma or red blood cells (RBCs).
      Although a few studies have reported on reproducibility of individual fatty acid
      measurements, the comprehensive analysis of intra-individual LCFA variability has
      not been performed. Therefore, our goal was to determine intra-individual
      variability for the 22 most abundant LCFAs in both plasma and RBC samples
      collected from healthy individuals on a regular diet after overnight fasting. The
      measurements of LCFAs in RBCs were consistent throughout the course of study
      reflecting long-term nutritional status. In contrast, the results in plasma
      showed considerable LCFA intra-individual variability, even between fatty acids
      of the same type. Plasma intra-individual variability for omega-3 alpha-linolenic
      and eicosapentaenoic acids in some participants were >40% whereas the variability
      of docosahexaenoic acid was consistently <12.8%. Omega-6 linoleic and arachidonic
      acids also showed low variability in plasma. The results suggest that some LCFAs
      have less variability and would be more reliable as biomarkers. Reliability of
      biomarkers can have a profound impact on the research outcomes. Intra-individual
      variability of LCFAs should be taken into consideration in designing, conducting
      and interpreting results of clinical studies.

PMID- 30103930
TI  - An association between the BanI polymorphism of the PLA2G4A gene for calcium
      dependent phospholipase A2 and plasma glucose levels among females with
      schizophrenia.
AB  - Abnormal glucose and lipid metabolism may be associated with altered cytosolic
      Ca2+-dependent phospholipase A2 (cPLA2) signaling in patients with schizophrenia.
      The relationship between schizophrenia and the functional BanI polymorphism
      (rs10798059 variant, A/G polymorphism) of the PLA2G4A gene for cPLA2 has been
      extensively investigated. We previously reported that it can influence several
      clinical features of schizophrenia, and it was shown to contribute to
      schizophrenia risk in several population studies. We performed PCR/RFLP
      genotyping of 263 Croatian patients (males/females: 139/124) to investigate the
      relationship between the BanI polymorphism and fasting plasma glucose and lipid
      levels in patients with schizophrenia. Our results indicate that the BanI
      polymorphic variant contributes significantly to plasma glucose levels in female
      patients. Females carrying the PLA2G4A-G allele (PLA2G4A-GG homozygous and
      PLA2G4A-AG heterozygous) presented with lower glucose levels than PLA2G4A-AA
      homozygous carriers, and the PLA2G4A genotype contributed approximately 6% of
      plasma glucose level variability in this group of patients.

PMID- 30103926
TI  - Ischemia-modified albumin: Crosstalk between fatty acid and cobalt binding.
AB  - Myocardial ischemia is difficult to diagnose effectively with still few well
      defined biochemical markers for identification in advance, or in the absence of
      myocardial necrosis. "Ischemia-modified albumin" (IMA), a form of albumin
      displaying reduced cobalt-binding affinity, is significantly elevated in ischemic
      patients, and the albumin cobalt-binding (ACB) assay can measure its level
      indirectly. Elucidating the molecular mechanism underlying the identity of IMA
      and the ACB assay hinges on understanding metal-binding properties of albumin.
      Albumin binds most metal ions and harbours four primary metal binding sites: site
      A, site B, the N-terminal site (NTS), and the free thiol at Cys34. Previous
      efforts to clarify the identity of IMA and the causes for its reduced cobalt
      binding capacity were focused on the NTS site, but the degree of N-terminal
      modification could not be correlated to the presence of ischemia. More recent
      work suggested that Co2+ ions as used in the ACB assay bind preferentially to
      site B, then to site A, and finally to the NTS. This insight paved the way for a
      new consistent molecular basis of the ACB assay: albumin is also the main plasma
      carrier for free fatty acids (FFAs), and binding of a fatty acid to the high
      affinity site FA2 results in conformational changes in albumin which prevent
      metal binding at site A and partially at site B. Thus, this review advances the
      hypothesis that high IMA levels in myocardial ischemia and many other conditions
      originate from high plasma FFA levels hampering the binding of Co2+ to sites A
      and/or B. This is supported by biophysical studies and the co-association of a
      range of pathological conditions with positive ACB assays and high plasma FFA
      levels.

PMID- 30103931
TI  - Increased docosahexaenoic acid and n-3 polyunsaturated fatty acids in milk from
      mothers of small for gestational age preterm infants.
AB  - The study aimed to test whether or not milk fatty acid composition in mothers of
      small for gestational age (SGA) infants is similar to that in mothers of adequate
      for gestational age (AGA) infants. Thirty three mothers of SGA preterm infants
      and 66 mothers of AGA preterm infants were included. Milk and plasma fatty acids
      were analyzed using capillary gas chromatography. Milk DHA (0.68 +/- 0.37 vs.
      0.44 +/- 0.24; p < 0.01) was higher and n-6:n-3 PUFA ratio (12.0 +/- 4.64 vs.
      16.0 +/- 6.32; p < 0.05) was lower in mothers of SGA infants. Plasma ARA and DHA
      were increased in mothers of SGA infants and decreased in their infants. Milk ARA
      or DHA was positively related to the correspondent fatty acid in plasma (r =
      0.374, p = 0.010 for ARA and r = 0.690, p < 0.001 for DHA). Breast milk in
      mothers of preterm infants born SGA is enriched in DHA and n-3 PUFA.
      Breastfeeding SGA preterm infant with own mother's milk is recommended.

PMID- 30103932
TI  - Long-chain omega-3 fatty acids and headache in the U.S. population.
AB  - : The objective of this study was to assess whether dietary intake of long-chain
      omega-3 polyunsaturated fatty acids (PUFAs) is associated with lower prevalence
      of headache in the U.S. POPULATION: This cross-sectional study used data for a
      nationally representative sample of 12,317 men and women aged >= 20 years
      participating in the National Health and Nutrition Examination Surveys of 1999
      2004. Interviewers recorded self-report of severe headache or migraine in the
      past three months. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)
      were quantified from 24-hour dietary recall using the U.S. Department of
      Agriculture National Nutrient Database. Serum concentration of C-reactive
      protein, a marker of inflammation and potential mediator of PUFA's analgesic
      properties, was quantified by latex-enhanced nephelometry. Multivariable
      generalized linear models estimated prevalence ratios (PR) with 95% confidence
      limits (CL) for severe headache or migraine adjusting for NHANES cycle,
      sociodemographic characteristics, body mass index and total energy intake. The
      unadjusted prevalence of severe headache or migraine was 22.0% (females 28.2%,
      males 15.5%). In multivariable analysis, greater intake of omega-3 PUFAs was
      associated with lower prevalence of severe headache or migraine: PR 0.94 (95% CL:
      0.88, 0.99, p = 0.035) per log unit increase in EPA, and PR 0.94 (95% CL: 0.90,
      0.99, p = 0.023) per log unit increase in DHA. The strength of association was
      greater for non-Mexican Hispanics than for other racial/ethnic groups but was not
      attenuated after adjustment for C-reactive protein. In conclusion, higher dietary
      intakes of EPA and DHA were associated with lower prevalence of headache
      supporting the hypothesis that omega-3 PUFAs may prevent or reduce headache.

PMID- 30103933
TI  - Dietary n-6 polyunsaturated fatty acids and cardiovascular disease: Epidemiologic
      evidence.
AB  - Epidemiologists have been studying the effect of n-6 polyunsaturated fatty acids
      (PUFAs) intake on the risk of cardiovascular disease (CVD) for many decades.
      Abundant evidence from prospective studies on the clinical endpoints of CVD,
      including cohort studies measuring n-6 PUFA intake by food frequency
      questionnaires and nested case-control studies using biomarkers of intake level,
      strongly support that higher intakes of n-6 PUFAs are associated with a lower
      risk of CVD. Furthermore, a significant reduction in CVD risk can be achieved
      when saturated fatty acids (SFAs) is replaced by n-6 PUFAs. Evidence from
      appropriately designed and vigorously executed randomized controlled trials
      support that high-PUFA (predominantly linoleic acid) and low-SFA diets, compared
      to high-SFA diets, reduced the risk of coronary heart disease. Overall,
      epidemiologic studies provide a solid evidence base of the current dietary
      guidelines that recommend replacing SFA by PUFA, both n-6 and n-3 PUFA, for CVD
      prevention.

PMID- 30103934
TI  - Influence of maternal consumption of different types of fatty acids during
      pregnancy and lactation on lipid and glucose metabolism of the 21-day-old male
      offspring in rats.
AB  - We evaluated the impacts of maternal consumption of different types of fatty
      acids during pregnancy and lactation on the lipid and glucose metabolism of 21
      day-old offspring. Rats received either control (C), saturated (SFAs), trans
      (TFAs) or n - 3 polyunsaturated (PUFAs) normolipidic diets throughout pregnancy
      and lactation. 21-day old male pups constituted the groups: C21, S21, T21 and
      PUFA21. At 21st day, serum parameters, hepatic triacylglycerol (TAG) deposition,
      oral glucose tolerance test (OGTT) and liver protein expressions were
      investigated. We found a decrease in serum concentrations of TAG, total
      cholesterol and FFA as well as in hepatic TAG content and baseline glycaemia,
      accompanied by an increase in catalase expression in PUFA21 group. In T21 group,
      OGTT showed slight disturbance in glucose homeostasis. Summarily, while early
      exposure to TFAs-based diets seems to harm pups' glucose homeostasis, maternal
      consumption of n - 3 PUFAs can improve lipid metabolism, TAG hepatic accumulation
      and catalase protein expression in 21-day-old offspring.

PMID- 30103935
TI  - Role of metabolic programming in the modulation of microglia phagocytosis by
      lipids.
AB  - Microglia phagocytosis is an essential process to maintain lifelong brain
      homeostasis and clear potential toxic factors from the neuropil. Microglia can
      engulf cells or part of cells through the expression of specific receptors at
      their surface and activation of downstream signaling pathways to engulf material.
      Microglia phagocytosis is finely regulated and is under the dependence of many
      factors, including environmental cues such as dietary lipids. Yet, the molecular
      mechanisms implicated are still largely unknown. The present publication is a
      'hypothesis review', assessing the possibility that lipid-mediated modulation of
      phagocytosis occurs by affecting bioenergetic pathways within microglia. I assess
      our present knowledge and the elements that allow drawing such hypothesis. I also
      list some of the important gaps in the literature that need to be filled in. I
      also consider opportunities for future therapeutic target including nutritional
      interventions.

PMID- 30103936
TI  - DHA-enriched re-esterified triacylglycerol fish oil supplementation and oily fish
      consumption enhance red blood n-3 fatty acid index in Omani pre-adolescent
      schoolchildren.
AB  - Dietary habits of Omani population particularly of children and young adults have
      changed significantly. Consumption of imported calorie-dense foods, vegetable
      oils, milled and polished grains and carbonated beverages have become the norm.
      Concomitantly, there has been an exponential increase in the prevalence of non
      communicable diseases. The impact of the westernisation of eating habits on
      children has not been evaluated. We have investigated blood fatty acid profile of
      male (n = 125) and female (n = 160) children aged 9 and 10 (9.8 +/- 0.4) years
      enrolled from three state-funded schools. The schools, which are homogenous with
      respect to socio-economic background of their pupils, were randomised into fish
      oil (n = 98), oily fish (n = 82) or control (n = 105) group. Subsequently, the
      children were given during morning tea break for 12 weeks: 1. DHA-enriched re
      esterified triacylglycerol fish oil capsule with cheese/salad sandwich (fish oil
      group), 2. Lightly grilled oily fish with salad (fish group) or 3. Cheese/salad
      sandwich (control group). At baseline, the males had higher myristic, palmitic
      and oleic and lower adrenic acids than the females (p < 0.05). There was no
      difference in n-3 fatty acid index (4.86 +/- 1.95 vs. 5.12 +/- 1.67, p > 0.05) or
      AA (14.6 +/- 1.9 vs. 14.9 +/- 1.8, p > 0.05) between the genders. There was no
      difference in any of the fatty acids between the three groups at baseline. Post
      intervention, the oily fish group had lower n-3 fatty acid index (EPA + DHA, 6.03
      +/- 1.39 vs. 6.60 +/- 1.63, p < 0.05) and higher AA (15.2 +/- 1.8 vs. 13.7 +/-
      2.0, p = 0.0001) and n-3 DPA (1.40 +/- 0.27 vs. 1.07 +/- 0.22, p = 0.0001)
      compared with those who received fish oil capsules. In both the fish oil and oily
      fish groups, fatty acid index correlated positively with AA (r = 0.394, p =
      0.0001; r = 0.231, p = 0.038) and negatively with total saturated (r = - 0.816, p
      = 0.0001; r = - 0.439, p = 0.0001) and total mono-unsaturated (r = - 0.431, p =
      0.0001; r = - 0.231, p = 0.037) fatty acids. Although seafood is an integral part
      of traditional Omani cuisine the children had a low level of n-3 fatty acids
      index. There is a need to address this nutritional insufficiency through school
      feeding programme, targeted intervention with n-3 fatty acid enriched food
      products and/or family education programme.

PMID- 30103937
TI  - Dietary n-3 but not n-6 fatty acids down-regulate maternal dyslipidemia induced
      inflammation: A three-generation study in rats.
AB  - This study addresses the effects of n-3 and n-6 fatty acids in maternal
      dyslipidemia induced inflammation over three generation in rats. The detailed
      protocol for animal feeding and mating is described in the methodology. Placenta
      and fetal liver were isolated on the eighteenth day of gestation and delivered
      pups after lactation were kept on their maternal diets. Compared to control and
      experimental groups, high-fat fed rats (HFL) had a higher level of cytokines and
      eicosanoids in serum (p < 0.05). Liver and uterine expression of cPLA-2, Cox-2, 5
      Lox, EP-1, BLT-1, and ICAM-1 were higher (p < 0.05) in HFL group. NF-kB and Nrf-2
      levels in placenta and fetal liver were beneficially modulated by n-3 but not n-6
      fatty acids. Offspring of dyslipidemic mothers' exhibit amplified inflammatory
      markers when continued on diets of their mothers. Incorporation of n-3 but not n
      6 fatty acids down-regulated maternal dyslipidemia induced inflammatory markers.

PMID- 30103938
TI  - Effect of complementary food with small amounts of freshwater fish on whole blood
      n-3 fatty acids in Cambodian infants age 6-15 months.
AB  - The impact of freshwater fish consumption on the status of long-chain n-3 fatty
      acids (n-3 LCPUFA) in infants in landlocked, low-income populations is unknown.
      We used secondary data from a randomized, single-blinded, controlled trial to
      evaluate the impact of daily consumption of complementary food products with
      small amounts of freshwater fish on whole blood n-3 LCPUFA in Cambodian infants.
      Infants (n = 419), received daily, one of four food products for 9 months. Two
      products contained freshwater fish: WinFood (10% fish by dry weight) and WinFood
      L (12% fish by dry weight), while two products were non-fish-based: corn-soy
      blends (CSB+ and CSB++). Whole blood fatty acids and breastfeeding status were
      assessed at baseline and endline of the intervention. The WinFood products
      contributed to an estimated maximum intake of 86.5 mg/day n-3 LCPUFA. There was
      no difference in whole blood n-3 LCPUFA among the four intervention groups or
      between the fish-based and the non-fish-based groups (p >= 0.142). At endline,
      71% of the children were still breastfed. Interaction analyses indicated a lower
      ratio of n-6/n-3 PUFA in non-breastfed infants in the WinFood groups compared to
      the CSB groups (pinteraction = 0.026). Thus, a high intake of n-3 LCPUFA from
      breastmilk may have blurred a potential impact of small amounts of freshwater
      fish effect on n-3 LCPUFA status in Cambodian infants.

PMID- 30103939
TI  - [Subcontracting a steam sterilization activity: Impact on surgical instruments].
AB  - Subcontracting our institution's sterilization activity induced the
      implementation of an automated cleaning facility. Following this development,
      some of the resterilizable stainless steel needle holders started to show
      abnormal corrosion. Our study goal was to investigate the causes of this
      corrosion in order to optimize the sterilization circuit. A full sterilization
      process mapping and Ishikawa diagram enabled us to identify potential causes of
      corrosion. The needle holders' intrinsic characteristics, like steel quality and
      manufacturing, were analyzed as well as extrinsic factors such as the influence
      of preprocessing soaking conditions, steel passivation, water quality and the
      impact of corrosion inhibitors. Each potential factor of corrosion was tested in
      real conditions on needle holders' kits. The needle holders steel grade complies
      with medical standards and the tests showed that passivation and pre-processing
      conditions were not involved in the occurrence of corrosion, contrary to soaking
      length and use of softened rinsing water, containing more chloride than reverse
      osmosis water, and, thus conducive to rust formation. Moreover, corrosion
      inhibitors were deemed ineffective or incompatible. Due to this analysis, the
      incidence of corrosion was reduced by switching softened water to osmosis water
      and by introducing dynamic drying in the automated cleaning process. In addition,
      this work stresses the importance of minimizing waiting times and auditing the
      sterilization circuit before any subcontracting. Management Guidelines related to
      sterilization's outsourcing would probably have helped to limit this episode.

PMID- 30103940
TI  - [How to measure real-world effectiveness?]
AB  - The new use of medico-administrative databases is a major change in the medical
      assessment field. Given the limits of the randomized clinical trials when it
      comes to accurately represent the heterogeneity and complexity of medical care in
      a real-world context, an increasing demand of observational studies comes from
      healthcare systems as decision tools. The lack of intervention generates real
      world data and assesses both the care and the outcomes of patients in routine
      practice. Despite this external validity, the bias and confounding factors are a
      challenge to the internal validity of observational studies. An appropriate study
      design and statistical methods are necessary to neutralize them and consider a
      causal relationship between a treatment and a clinical outcome.

PMID- 30103942
TI  - Fatty acid activates NLRP3 inflammasomes in mouse Kupffer cells through
      mitochondrial DNA release.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in many
      developed and developing countries worldwide. It has been well established that
      the chronic sterile inflammation caused by the NLRP3 inflammasome is closely
      related to NAFLD development. Kupffer cells (KCs) are involved in the
      pathogenesis of various liver diseases. We used methionine choline-deficient
      diets to establish a mouse nonalcoholic steatohepatitis (NASH) model. The
      expression and formation of the NLRP3 inflammasome in the KCs from the mouse and
      cell models were determined by Western blotting and co-immunoprecipitation.
      Evidence of mitochondrial DNA (mtDNA) release was determined by live cell
      labeling and imaging. KCs and the NLRP3 inflammasome exerted proinflammatory
      effects on the development and progression of NASH through secretion of the
      proinflammatory cytokine IL-1beta. NLRP3, ASC and Caspase-1 protein expression
      levels in KCs from NASH mouse livers were significantly higher than those in KCs
      from NLRP3-/- mice, and the number of NLRP3 inflammasome protein complexes was
      significantly higher in KCs from NASH mouse livers, whereas these protein
      complexes could not be formed in NLRP3-/- mice. In in vitro experiments, palmitic
      acid (PA) decreased the mitochondrial membrane potential and subsequently induced
      mtDNA release from the mitochondria to the cytoplasm. NLRP3 inflammasome
      expression was substantially increased, and mtDNA-NLRP3 inflammasome complexes
      formed upon PA stimulation. Our data suggest that mtDNA released from
      mitochondria during PA stimulation causes NLRP3 inflammasome activation,
      providing a missing link between NLRP3 inflammasome activation and NASH
      development, via binding of cytosolic mtDNA to the NLRP3 inflammasome.

PMID- 30103943
TI  - Down-regulated lncRNA MEG3 promotes osteogenic differentiation of human dental
      follicle stem cells by epigenetically regulating Wnt pathway.
AB  - Our previous long noncoding RNA (lncRNA) microarray results showed that lncRNA
      MEG3 (maternally expressed 3) was significantly downregulated in human dental
      follicle cells than human periodontal ligament cells. Latest studies show that
      MEG3 contributes to polycomb repressive complex 2 (PRC2) recruitment to silence
      gene expression. The enhancer of zeste homolog 2 (EZH2), a crucial catalytic
      subunit of PRC2, mediates gene silencing and participates in cell lineage
      determination via methyltransferase activity. In this study, we found that the
      expression of EZH2 and H3K27me3 (trimethylation on lysine 27 in histone H3)
      decreased during osteogenesis of human dental follicle stem cells (hDFSCs).
      Knockdown studies of MEG3 and EZH2 by siRNA showed that MEG3/EZH2 negatively
      regulated osteogenesis of hDFSCs. We investigated the role of Wnt signaling
      pathway during the osteogenesis of hDFSCs and its relationship with EZH2.
      Besides, we studied the key genes of the canonical/noncanonical Wnt signaling
      pathway which might be related to EZH2. ChIP (chromatin immunoprecipitation)
      analysis showed that these effects were due to the EZH2 regulation of H3K27me3
      level on the Wnt genes promotors. We first demonstrated that the decrease of MEG3
      or EZH2 activated the Wnt/beta-catenin signaling pathway via epigenetically
      regulating the H3K27me3 level on the Wnt genes promotors. Our research offers a
      new target for periodontal tissue engineering and osteogenic tissue regeneration.

PMID- 30103941
TI  - Anti-LFA-1 induces CD8 T-cell dependent allograft tolerance and augments
      suppressor phenotype CD8 cells.
AB  - The induction of tolerance to transplanted organs is a major objective in
      transplantation immunology research. Lymphocyte function-associated antigen-1
      (LFA-1) interactions have been identified as a key component of the T-cell
      activation process that may be interrupted to lead to allograft tolerance. In
      mice, alphaLFA-1 mAb is a potent monotherapy that leads to the induction of donor
      specific transferable tolerance. By interrogating important adaptive and innate
      immunity pathways, we demonstrate that the induction of tolerance relies on CD8+T
      cells. We further demonstrate that alphaLFA-1 induced tolerance is associated
      with CD8+CD28-T-cells with a suppressor phenotype, and that while CD8 cells are
      present, the effector T-cell response is abrogated. A recent publication has
      shown that CD8+CD28- cells are not diminished by cyclosporine or rapamycin,
      therefore CD8+CD28- cells represent a clinically relevant population. To our
      knowledge, this is the first time that a mechanism for alphaLFA-1 induced
      tolerance has been described.

PMID- 30103944
TI  - c-Myc-driven glycolysis via TXNIP suppression is dependent on glutaminase-MondoA
      axis in prostate cancer.
AB  - Oncogenic c-Myc-induced metabolic reprogramming triggers cellular dependency on
      exogenous glucose and glutamine. Understanding how nutrients are used may provide
      new target for therapeutic intervention. We previously provided an alternate
      route to c-Myc-driven glucose metabolism via the repression of thioredoxin
      interacting protein (TXNIP), which is a potent negative regulator of glucose
      uptake. Herein, we demonstrate that c-Myc suppression of TXNIP is predominantly
      through the activation of glutaminolysis via glutaminase (GLS1) in prostate
      cancer cells. Glutamine depletion blocked c-Myc-dependent reductions of TXNIP and
      its principal regulator MondoA transcriptional activity. Further, GLS1 inhibition
      by either siRNA or CB-839 resumed TXNIP expression that was repressed by c-Myc.
      The TXNIP promoter with mutant E-Box region, which was recognized by MondoA,
      failed to respond to c-Myc or GLS1, indicating c-Myc repression of TXNIP by GLS1
      is predominantly through the blockage of MondoA activity. Especially, ectopic
      TXNIP expression decreased c-Myc-induce glucose uptake and lead to a broad range
      of glycolytic target gene suppressions. Thus TXNIP is a key adaptor for c-Myc
      driven aerobic glycolysis. Supporting the biological significance of c-Myc and
      TXNIP, their reciprocal relationship are correlates with patient outcome and
      contributes to the aggressive phenotype in PCAs.

PMID- 30103945
TI  - Staufen1, Kinesin1 and microtubule function in cyclin B1 mRNA transport to the
      animal polar cytoplasm of zebrafish oocytes.
AB  - In zebrafish oocytes, cyclin B1 mRNAs are transported to the animal polar
      cytoplasm. To elucidate the molecular basis of cyclin B1 mRNA transport, we
      analyzed zebrafish Staufen1, a protein known to play a central role in mRNA
      transport to the vegetal pole of Xenopus oocytes. Zebrafish Staufen1 interacts
      with cyclin B1 mRNA throughout oocyte growth. Both cyclin B1 mRNA and Staufen1
      are evenly distributed in the cytoplasm of young oocytes but are co-localized to
      the animal polar cytoplasm in later stages. Real-time imaging showed that the
      plus ends of oocyte microtubules are free in the cytoplasm in early stages but
      anchored to the animal polar cytoplasm in later stages. Transport of cyclin B1
      reporter mRNA to the animal polar cytoplasm was inhibited by disruption of
      microtubules and injection of antibodies against Staufen1 or Kinesin1, a plus-end
      directed microtubule motor that interacts with Staufen1, indicating that the
      transport depends on movement along microtubules toward the plus ends. Reporter
      mRNAs with an element required for the vegetal localization of vg1 mRNA in
      Xenopus oocytes were localized to the animal polar cytoplasm in zebrafish
      oocytes, indicating that the element is functional for animal polar localization
      in zebrafish oocytes. Our findings suggest that cyclin B1 mRNA-Staufen1 protein
      complexes are transported toward the animal pole of zebrafish oocytes by the plus
      end-directed motor protein Kinesin1 along microtubules and that a common mRNA
      transport machinery functions in zebrafish and Xenopus oocytes, although its
      transport direction is opposite due to different organizations of microtubules.

PMID- 30103946
TI  - Upregulated circular RNA circ_0016760 indicates unfavorable prognosis in NSCLC
      and promotes cell progression through miR-1287/GAGE1 axis.
AB  - Non-small cell lung cancer (NSCLC) is an aggressive malignancy with increasing
      worldwide incidence and is characterized by dismal prognosis due to its early
      recurrence and metastasis. Accumulating evidence documented that aberrantly
      expressed circular RNAs (circRNAs) are critically involved in tumorigenesis. In
      the current study, we focused on a novel circRNA, circ_0016760 in NSCLC. qRT-PCR
      was carried out to determine the expression level of circ_0016760 in tissue
      samples and cell lines. The clinical value of circ_0016760 was also investigated.
      The functions of circ_0016760 was explored by CCK-8, colony formation, flow
      cytometry, Transwell and animal experiments. Luciferase reporter assays were
      conducted to investigate the association between circ_0016760 and miR-1287 and
      miR-1287 and GAGE1. We found that circ_0016760 was enhanced in NSCLC tissues and
      cells and the upregulation of circ_0016760 is associated with advanced TNM
      stages, lymph node metastasis and adverse prognosis in NSCLC patients. Moreover,
      circ_0016760 could significantly promote cell growth and metastatic properties
      and inhibit cell apoptosis in NSCLC cells. In mechanism, circ_0016760 functioned
      as a sponge for miR-1287 and regulated the expression of GAGE1. Subsequently,
      functional assays illustrated that the oncogenic properties of circ_0016760 is
      partly attribute to the regulation of miR-1287/GAGE1 axis. In summary,
      circ_0016760/miR-1287/GAGE1 signaling might play vital roles in the tumorigenesis
      and progression of NSCLC.

PMID- 30103947
TI  - Role of c-Myb in the regulation of natural killer cell activity.
AB  - The regulation of natural killer (NK) cell activity is an important research goal
      for the development of immunotherapies. In this study, we identified
      transcription factors affecting NK cell activity. In particular, we screened
      transcription factors affected by interleukin-2 (IL-2) and transforming growth
      factor-beta (TGF-beta) by protein/DNA arrays using primary NK cells. We found
      that celastrol, a c-Myb inhibitor, inhibited NK-92 cells more strongly than any
      other inhibitors of transcription factor candidates. In addition, c-Myb and c-Myb
      related signaling molecules, e.g., Nemo-like kinase (NLK) and c-Myc, were
      regulated by the activation status of NK cells, suggesting that c-Myb is a key
      regulator of NK cell activity. We also found that celastrol inhibits NK-92-cell
      mediated cytotoxicity via the downregulation of NKG2D and granzyme B. Knockdown
      studies also showed that c-Myb is important for NK cell activation. In
      particular, the knockdown of c-Myb did not significantly affect NK cell
      proliferation and survival but decreased the secretion of IFN-gamma and the
      cytotoxicity of NK cells. Our data demonstrate that c-Myb plays a critical role
      in the activation of NK cells and therefore is a therapeutic target for cancer
      and viral diseases.

PMID- 30103948
TI  - Assessment of the flagellar redox potential in Chlamydomonas reinhardtii using a
      redox-sensitive fluorescent protein, Oba-Qc.
AB  - Cellular reducing-oxidizing (redox) potential is mainly determined by the
      concentration ratio between reduced and oxidized glutathiones. It is normally
      kept at a moderately reduced state but affected to some extent by metabolic
      activities such as respiration and/or photosynthesis. Changes in redox potential
      induce many cellular activities collectively called redox responses. For an
      understanding of the dynamics of the cellular redox responses, redox potential
      must be accurately assessed in vivo. In this study, we developed a method to
      measure the in vivo redox potential in the green alga Chlamydomonas reinhardtii,
      using Oba-Qc, a recently developed redox-monitoring protein. Taking advantage of
      the periodic flagellar assembly, we introduced Oba-Qc molecules into the flagella
      at a constant density. Fluorescence signals from flagella in live cells,
      calibrated against the fluorescence from the samples in buffers of known redox
      potentials, determined the redox potential to be ~-250 mV in the light and ~-280
      mV in the dark. Introduction of a sensor protein fused with a structural protein
      that assembles at a constant density will be also applicable for measurements of
      various kinds cellular signals in flagella.

PMID- 30103949
TI  - c-Fos is necessary for HGF-mediated gene regulation and cell migration in Schwann
      cells.
AB  - We previously reported that the expression of hepatocyte growth factor (HGF) was
      highly induced after peripheral nerve damage, and that c-Fos is one of many
      cellular genes whose expressions are affected by the increased level of HGF[1]. c
      Fos is an important component of AP-1 heterodimer, but its role has not been
      clearly understood in the context of HGF and Schwann cells (SCs). In this study,
      we investigated the relationship between HGF and c-Fos. First, it was confirmed
      that the c-Fos was increased in SCs after nerve injury, while this effect
      abrogated by PHA-665752, an inhibitor of c-met receptor. When primary SCs were
      treated with recombinant HGF protein, c-Fos expression was regulated in a typical
      quick, transient fashion at both RNA and proteins levels. HGF-mediated induction
      of c-Fos expression was highly suppressed by specific inhibitors of ERK and CREB,
      respectively. The knock down of c-Fos expression by siRNA almost completely
      blocked various HGF-mediated effects in SCs, such as induction of gene expression
      of GDNF, LIF, and c-Myc, and migration of SCs, indicating that c-Fos might play a
      key role in HGF effects. Taken together, our results suggested that c-Fos plays a
      key role(s) in HGF-mediated effects on neurotrophic genes and cell migration.

PMID- 30103950
TI  - Inhibition of TRAF6 alleviates choroidal neovascularization in vivo.
AB  - Choroidal neovascularization (CNV) is a type of wet age-related macular
      degeneration (AMD) which is a major cause of blindness in elder patients. Tumor
      necrosis factor receptor-associated factor 6 (TRAF6) promotes tumor angiogenesis
      via upregulating the expression of hypoxia-inducible factor 1alpha (HIF-1alpha)
      and vascular endothelial growth factor (VEGF). Additionally, TRAF6 facilitates
      the inflammatory response in macrophages and microglia. Here, using mouse laser
      induced CNV model and TRAF6 siRNA, the study shows that TRAF6 is a critical
      player in CNV. The expression of TRAF6, HIF-1alpha, and VEGF increased in the
      model. TFAF6 siRNA intravitreal (IVT) injection inhibited CNV formation, as well
      as expression of HIF-1alpha and VEGF, activation of macrophages and microglia.
      Together, our data suggest that TFAF6 inhibition reduces CNV formation via down
      regulating expression of HIF-1alpha and VEGF and activation of macrophages and
      microglia, demonstrating the unique advantages of TRAF6 inhibition in the
      alleviation of AMD.

PMID- 30103952
TI  - Lower limb apraxia in corticobasal syndrome.

PMID- 30103951
TI  - The Potential of Repetitive Transcranial Magnetic Stimulation for Autism Spectrum
      Disorder: A Consensus Statement.

PMID- 30103953
TI  - Fluctuating CSF hypocretin-1 levels in mild brain trauma-induced Kleine-Levin
      syndrome.

PMID- 30103954
TI  - Frequency and features of the central poststroke pain.
AB  - BACKGROUND: Central poststroke pain (CPSP) is often unrecognized in clinical
      practice, it may aggravate the rehabilitation process and reduce quality of life.
      AIM: To determine the frequency and features of CPSP, as well as to make possible
      associations of CPSP with sociodemographic and clinical features of subjects with
      stroke. METHOD: In a two-year period 602 patients with previous stroke were
      consecutively tested. We used three questionnaires for the diagnosis of
      neuropathic pain (Pain Detect Questionnaire - PD-Q, The Leeds Assessment of
      Neuropathic Symptoms and Signs - LANSS and Douleur neuropatathique en 4 questions
      - DN4). RESULTS: CPSP was present in 12% of our patients with stroke, and usually
      occurred in the first several months after stroke. It was associated with
      cortical and thalamic localization of stroke, higher level of functional
      disability, as well as with younger age. The most important features that
      distinguish CPSP from other types of pain were presence of allodynia and pricking
      hypoesthesia, while other neuropathic sensations were common in stroke subjects
      both with and without CPSP. CONCLUSION: Younger subjects with cortical/thalamic
      stroke and higher level of disability should be thoroughly examined for the
      presence of neuropatic pain, since this may highly influence therapeutic strategy
      and quality of life in these subjects.

PMID- 30103955
TI  - Epilepsy treatment patterns among patients with tuberous sclerosis complex.
AB  - INTRODUCTION: Tuberous sclerosis complex (TSC) is a rare congenital disorder
      often associated with epilepsy. However, real-world treatment patterns for
      epilepsy in patients with TSC are not yet well categorized. METHODS: This study
      included patients with TSC and epilepsy from fifteen clinics in the United States
      and one in Belgium who were enrolled in the TSC Natural History Database (2006
      2014). Patient demographics and epilepsy treatment patterns, including the use of
      anti-epileptic drugs (AEDs), epilepsy surgeries, and dietary therapies were
      assessed. RESULTS: Of the 1328 patients with TSC in the database, 1110 (83.6%)
      were diagnosed with epilepsy. The median age of epilepsy diagnosis was 0.7 years.
      Of those who received treatment for epilepsy (92.3%), 99.5% were prescribed AEDs,
      25.3% underwent surgery, 7.9% were prescribed special diets, and 1% were
      prescribed mammalian target of rapamycin (mTOR) inhibitors. Of the patients
      receiving AEDs, over half (64.5%) used >=3 different AEDs, and 22.5% underwent
      surgical treatment following AED initiation. Of the patients who underwent
      surgery, 35.1% had subsequent surgery. CONCLUSION: The use of multiple AEDs and
      surgical interventions may indicate a need for new therapies to reduce the
      treatment burden among patients with TSC and epilepsy.

PMID- 30103956
TI  - Teleneurology in sub-Saharan Africa: Experience from a long lasting HIV/AIDS
      health program (DREAM).

PMID- 30103957
TI  - A novel mutation in the valosin-containing-protein gene found in a Spanish
      family.

PMID- 30103958
TI  - Age and gender differences in motor imagery.
AB  - BACKGROUND: Few studies have explored the effects of ageing and gender in the
      dimensions of motor imagery (MI) such as vividness (vivid images and sensations
      of mental movements) and timing (the duration of an imagined movement). This
      study aims 1) to investigate the effect of age and gender effect in vividness and
      timing capabilities on MI, and 2) to examine the relationship between these two
      dimensions of MI. METHODS: A population of 72 (47% of males) good imagers
      including 41 young subjects and 31 older subjects were assessed on MI vividness
      using the Vividness of Movement Imagery Questionnaire (VMIQ-2) and on MI timing
      using the performances of the real Timed Up and Go (rTUG) test and its imagined
      version (iTUG). The main outcome variables were the VMIQ-2 score and the delta
      TUG, i.e. the difference between rTUG and iTUG. RESULTS: Mental vividness was
      affected by ageing with a loss of visual dominance in favor of kinesthetic
      imagery in older subjects compared to younger ones; however, no difference
      between both groups was found in timing measured by delta-TUG. Vividness
      capabilities were similar between men and women, but women performed better in
      timing. VMIQ-2 scores were not associated with delta-TUG; only gender was
      significantly associated with delta-TUG. CONCLUSIONS: This study revealed 1) an
      age-related transfer from a visual to a kinesthetic MI ability, but no impact on
      timing of MI; 2) a gender effect on timing with no impact on mental vividness; 3)
      no association between vividness and timing capabilities.

PMID- 30103959
TI  - Some new proposals for the classification of inherited myopathies.

PMID- 30103960
TI  - Neurocardiac prodrome in LGI1-antibody-negative non-paraneoplastic limbic
      encephalitis.

PMID- 30103961
TI  - Plasma beta-amyloid1-42 reference values in cognitively normal subjects.
AB  - BACKGROUND: In clinical practice, the use of plasma beta-Amyloid1-42 (Abeta1-42)
      as biomarker for Alzheimer's disease is largely limited by the absence of
      reference values. The aim of this study was to evaluate Abeta1-42 plasma
      concentrations in cognitively normal subjects and to propose reference values.
      METHODS: Plasma samples were obtained from 245 subjects, with a wide age-range
      (19-89 years), enrolled at the Unit of Laboratory Medicine of the "Azienda
      Ospedaliera Cardinale G. Panico" (younger subjects) and from a population-based
      study on aging (GreatAGE study) (older subjects). Three different age-groups were
      established: young (<= 34), adult (35 <= age <= 64) and old (>64). The
      Innogenetics Elisa kit for plasma Abeta1-42 was used for the analysis. RESULTS:
      The mean (SD) concentration of plasma Abeta1-42 was 17.65 (5.71) pg/mL. A
      positive trend was found in Abeta1-42 levels across the three age groups (p <
      .0001): young subjects showed values of Abeta1-42 significantly lower than the
      adult group (p < .0001) and than the old one (p < .0001 overall); no significant
      differences were found between the adult and the old groups (p = 1.0000). For the
      entire cohort the lower limit of 90% Reference Interval, double-sided, was 8.12
      pg/mL (95% CI 6.77-9.45) and the upper limit was 29.00 pg/mL (95% CI 27.01
      31.00). CONCLUSION: The present study proposes reference values for plasma Abeta1
      42. Nevertheless, further studies are needed to confirm these results and
      corroborate the use of these reference values in clinical practice.

PMID- 30103962
TI  - Diffusion tensor imaging findings in the multiple sclerosis patients and their
      relationships to various aspects of disability.
AB  - BACKGROUND: The aim of the study was to assess microstructural changes within
      strategic brain regions in multiple sclerosis (MS) patients, using diffusion
      tensor imaging (DTI), with regard to various aspects of disability. MATERIAL AND
      METHODS: The study comprised 50 patients with relapsing-remitting MS (37 women,
      13 men, mean age 36.4 yrs) and 27 age- and sex-matched controls. Using DTI,
      fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were
      obtained within corpus callosum (CC), both thalami (TH) and middle cerebellar
      peduncles (MCP). Disability was assessed using Expanded Disability Status Scale
      (EDSS), MS Functional Composite (MSFC), Symbol Digit Modalities Test (SDMT) and
      Fatigue Severity Scale (FSS). DTI indices were compared between the patients and
      controls and in the MS group - referred to disability measures. RESULTS:
      Significant decrease in FA and increase in ADC within CC and both TH were found
      in MS patients compared to the controls. DTI indices within CC and TH correlated
      significantly with SDMT score, and within TH and MCP - with MSFC manual dexterity
      measure. CONCLUSIONS: Changes in DTI measures in normal appearing white and grey
      matter in the MS patients indicate subtle alterations of the tissue integrity. An
      occult damage to the strategic brain regions may contribute to various aspects of
      disability due to MS.

PMID- 30103963
TI  - Correlation between clinical and radiologic features of patients with Gerstmann
      Straussler-Scheinker syndrome (Pro102Leu).
AB  - BACKGROUND AND PURPOSE: Gerstmann-Straussler-Scheinker syndrome is a rare
      hereditary neurodegenerative disorder with clinical heterogeneity. This study is
      aim to demonstrate the clinical spectrum and radiologic characteristics of
      patients caused by Pro102Leu mutation in PRNP. MATERIALS AND METHODS: We
      retrospect clinical manifestations of five patients from four Japanese families,
      and comprehensively analyzed their brain MRI, SPECT (N-isopropyl-p-[123I]
      iodoamphetamine), and PET (18F-2-fluoro-2-deoxy-d-glucose) images. RESULTS: All
      patients developed ataxia of lower limbs and trunk, gait disturbance, dysesthesia
      in legs, and lower limb hyporeflexia. In the early clinical stage before dementia
      began, no noticeable abnormalities could be observed from brain MRI, but SPECT
      and PET revealed mosaic-like pattern of blood flow and glucose metabolism of the
      brain. Predominant abnormalities were found in the occipital and frontal lobes on
      SPECT and PET analysis, respectively. In SPECT analysis, blood flow of the
      anterior cerebellar lobes was lower than that of the posterior cerebellar lobes.
      CONCLUSIONS: Clinical symptoms resulting from failure of dorsal horn of spinal
      cord and spinocerebellar tracts were observed in all cases. Radiologic findings
      revealed individual differences of involved region in their brain, which could
      produce clinical diversity. We identified a downtrend of blood flow in the
      anterior cerebellar lobes, a projection field of the spinocerebellar tracts,
      which is an important feature of Gerstmann-Straussler-Scheinker syndrome.

PMID- 30103964
TI  - Fatal ischemic stroke caused by cerebral small arteritis in a patient with giant
      cell arteritis.

PMID- 30103965
TI  - Domain-specific characterisation of early cognitive impairment following
      spontaneous intracerebral haemorrhage.
AB  - Cognitive deficits after spontaneous intracerebral haemorrhage (ICH) are common
      and result in functional impairment, but few studies have examined deficits
      across cognitive domains in the subacute phase. This study aims to describe the
      cognitive profile following acute ICH and explore how cerebral amyloid angiopathy
      (CAA) may impact performance. We retrospectively reviewed 187 consecutive
      patients with ICH (mean age 58.9 years, 55.6% male) with available imaging and
      neuropsychological data (median 12 days after stroke). In our cohort, 84% (n =
      158) were impaired in at least one cognitive domain and 65% (n = 122) in two or
      more domains. Deficits in non-verbal IQ (76.6%), information processing speed
      (62.4%) and executive functions (58.1%) were most common. Patients with lobar ICH
      (n = 92) had more deficits in naming and visual perception than those with non
      lobar ICH, but not in adjusted analyses. Patients with probable CAA (n = 21) had
      more deficits in verbal IQ, visual perception and executive functions than those
      without probable CAA; in adjusted analyses, probable CAA predicted impairment in
      verbal IQ (OR 38.6, 95% CI 3.2 to 465.4, p = 0.004) and executive function (OR
      3.4, 95% CI 1.0 to 11.7, p = 0.050). We conclude that cognitive deficits
      following ICH are common across domains, and that those with CAA appear to have a
      different cognitive profile. Replication of this work in larger cohorts will be
      important for confirming and further quantifying these observations.

PMID- 30103966
TI  - Reversible sensory polyneuropathy during an arboviral outbreak in Salvador,
      Bahia, Brazil.

PMID- 30103967
TI  - Deep brain stimulation is effective in pediatric patients with GNAO1 associated
      severe hyperkinesia.
AB  - BACKGROUND: Exacerbation of hyperkinesia is a life-threatening complication of
      dyskinetic movement disorders, which can lead to multi-organ failure and even to
      death. GNAO1 has been recently identified to be involved in the pathogenesis of
      early infantile epileptic encephalopathy and movement disorders. Patients with
      GNAO1 mutations can present with a severe, progressive hyperkinetic movement
      disorder with prolonged life-threatening exacerbations, which are refractory to
      most anti-dystonic medication. OBJECTIVE: The objective was to investigate the
      evolution of symptoms and the response to deep brain stimulation of the globus
      pallidus internus (GPi-DBS) in patients with different GNAO1 mutations. METHODS:
      We report six patients presenting with global motor retardation, reduced muscle
      tone and recurrent episodes of severe, life-threatening hyperkinesia with
      dystonia, choreoathetosis, and ballism since early childhood. Five of them
      underwent GPi-DBS. RESULTS: The genetic workup revealed mutations in GNAO1 for
      all six patients. These encompass a new splice site mutation (c.723+1G>T) in
      patient 1, a new missense mutation (c.610G>C; p.Gly204Arg) in patient 2, a
      heterozygous mutation (c.625>T; p.Arg209Cys) in patients 3 and 4, and a
      heterozygous mutation (c.709G>A; p.Glu237Lys) in patients 5 and 6. By
      intervention with GPi-DBS the severe paroxysmal hyperkinetic exacerbations could
      be stopped in five patients. One patient is still under evaluation for
      neuromodulation. CONCLUSION: In complex movement disorders of unsolved etiology
      clinical WES can rapidly streamline pathogenic genes. We identified two novel
      GNAO1 mutations. GPi-DBS can be an effective and life-saving treatment option for
      patients with GNAO1 mutations and has to be considered early.

PMID- 30103968
TI  - Evaluation of the use of the Scale for the Assessment and Rating of Ataxia (SARA)
      in healthy volunteers and patients with schizophrenia.
AB  - OBJECTIVE: The Scale for the Assessment and Rating of Ataxia (SARA) is a semi
      quantitative assessment used to evaluate ataxia. The goal of these studies was to
      assess and evaluate the utility of this instrument in a Healthy Volunteer (HV)
      group and subjects with Schizophrenia (SCZ). METHODS: Two studies were completed
      to collect SARA data, in a HV group and in a stable SCZ group. 177 HVs (18-65
      years) and 16 SCZs (18-58 years) provided written consent and were assessed using
      the SARA. Of 177 HV subjects, 88 had 2 SARA assessments (within 2 days of initial
      visit) while all 16 SCZ had 3 SARA assessments (within 14 days of initial visit).
      RESULTS: For the HV group, the mean score +/- Std for the SARA on visit-1 was
      0.39 +/- 0.72, and 0.34 +/- 0.64 for visit-2. The Pearson correlation coefficient
      between visit-1 and visit-2 was 0.7486 and an ICC of 0.743. For the SCZ group,
      the mean score for the SARA was 0.63 +/- 0.65 on visit-1, 0.84 +/- 1.19 on visit
      2, and 0.84 +/- 0.94 on visit-3. The Pearson correlation coefficient between
      visit-1 and visit-2 was 0.6545, between visit-1 and visit-3 was 0.6635 and
      between visit-2 and visit-3 was 0.7613 and an ICC of 0.650. There was no
      significant difference in baseline SARA scores between the HV and SCZ group p =
      .063. A statistically significant positive association between age and total SARA
      scores was observed in HV (r = 0.345) and SCZ (r = 0.676). CONCLUSIONS: A strong
      association was observed in both the HV and SCZ groups in the reassessment of
      signs of ataxia using the SARA scale. Both groups demonstrated minimal signs of
      ataxia, with no statistically significant difference between the two groups in
      their visit-1 scores.

PMID- 30103969
TI  - Monitoring of structural changes in the course of acute compressive radial
      neuropathies by means of high resolution nerve ultrasound.

PMID- 30103970
TI  - Endovascular treatment of symptomatic vertebral artery stenosis: A systematic
      review and meta-analysis.
AB  - BACKGROUND: The study aim was to evaluate the safety and efficacy of endovascular
      treatment (EVT) versus medical treatment (MT) in patients with symptomatic
      vertebral artery (VA) stenosis. METHODS: Randomized controlled trials with active
      and control groups receiving EVT plus MT and MT alone in patients with vertebro
      basilar transient ischemic attack (TIA) or stroke and VA stenosis were
      identified. Primary endpoints included the occurrence of any stroke, any vertebro
      basilar stroke, vertebro-basilar ischemic stroke, and vertebro-basilar TIA.
      Secondary endpoints were myocardial infarction, vascular death, and composite
      vascular outcome. All endpoints were assessed at short and long-term. Risk ratios
      (RRs) with 95% confidence intervals (CIs) have been estimated. RESULTS: Four
      trials were included involving 370 participants, 194 and 176 for EVT and MT arms,
      respectively. There was no overall effect of EVT on the occurrence of any stroke
      [short-term: RR 3.05 (95% CI 0.33-28.49); long-term: RR 0.75 (95% CI 0.40-1.40)],
      any vertebro-basilar stroke [short-term RR 3.05 (95% CI 0.33-28.49); long-term RR
      0.91 (95% CI 0.42-1.99)], vertebro-basilar ischemic stroke [short-term: RR 1.02
      (95% CI 0.07-15.88); long-term RR 1.27 (95% CI 0.36-4.50)], vertebro-basilar TIA
      [short-term: RR 5.00 (95% CI 0.28-90.18); long-term: RR 0.85 (95% CI 0.39-1.81)].
      There were no differences across the treatments in any secondary outcome.
      CONCLUSIONS: There were no clear-cut benefits or harms for EVT versus MT alone in
      patients with symptomatic VA stenosis.

PMID- 30103972
TI  - The phenotype of idiopathic normal pressure hydrocephalus-a single center study
      of 429 patients.
AB  - INTRODUCTION: Idiopathic Normal Pressure Hydrocephlaus (iNPH) is, despite a
      vastly improved knowledge of the disorder since its first description still
      underdiagnosed and undertreated. Because of this, there is a need for further
      large studies describing the typical symptomatology and reversibility of symptoms
      in iNPH, which was the aim of this study. METHODS: In all, 429 patients (mean age
      71 years) were included. Detailed pre- and postoperative examinations of symptoms
      and signs were analyzed. A composite outcome measure was constructed. RESULTS:
      Sixty-eight % improved after surgery. Preoperatively, 72% exhibited symptoms from
      three or four of the assessed domains (gait, balance, neuropsychology and
      continence) while 41% had symptoms from all four domains. Ninety % had gait
      disturbances, of which 75% had broad-based gait, 65% shuffling gait and 30%
      freezing of gait. These disturbances coexisted in most patients preoperatively,
      but were more likely to appear as isolated findings after surgery. Impaired
      balance was seen in 53% and retropulsion in 46%. MMSE <25 was seen in 53% and
      impaired continence in 86%. Improvements were seen in all symptom domains
      postoperatively. CONCLUSIONS: The iNPH phenotype is characterized by a
      disturbance in at least 3/4 symptom domains in most patients, with improvements
      in all domains after shunt surgery. Most patients present with a broad-based and
      shuffling gait as well as paratonia. Present symptoms in all domains and a
      shuffling gait at the time of diagnosis seem to predict a favorable postoperative
      outcome, whereas symptom severity does not.

PMID- 30103971
TI  - Zonisamide cotreatment delays striatal dopamine transporter reduction in
      Parkinson disease: A retrospective, observational cohort study.
AB  - This study examined whether zonisamide (ZNS) cotreatment delays dopamine
      transporter (DAT) reduction on SPECT in Parkinson disease (PD) patients. The
      study participants met the following criteria: (i) age >= 40 years; (ii) HY stage
      = 2 or 3; (iii) average specific binding ratio (SBR) >=2.00; (iv) levodopa
      administration without a prior history of ZNS use before the first DAT-SPECT
      (baseline). Attending physicians initially determined whether ZNS (25 mg/day)
      should be used or not. Levodopa and other anti-PD medications were not
      restricted. The second DAT-SPECT (endpoint) was conducted 1.2 +/- 0.2 years after
      the first DAT-SPECT. Clinicoradiological changes of HY stage, UPDRS parts II to
      IV, dyskinesia subscore, and SBR were calculated. Statistical differences were
      analyzed by Student's t-test, ANOVA, or multilogistic analysis. ZNS cotreatment
      improved wearing off and prevented the development of dyskinesia without
      additional administration of selegiline, entacapone, and dopamine receptor
      agonists. The endpoint SBR reduced significantly in the non-ZNS group compared to
      the baseline (P < .01). The SBR decline rate reduced significantly in the ZNS
      group (P < .01). ZNS was an independent preventive factor for SBR reduction.
      These results suggested a beneficial potential that ZNS preserves striatal
      presynaptic DAT expression and slows disease progression in early-stage PD.

PMID- 30103973
TI  - Transitional imaging of bone destruction in invasive sinus aspergillosis
      masquerading as idiopathic optic neuropathy.

PMID- 30103974
TI  - Distinction between anti-VGKC-complex seropositive patients with and without anti
      LGI1/CASPR2 antibodies.
AB  - BACKGROUND: To identify clinical and paraclinical differences between anti
      voltage-gated potassium channel (VGKC)-complex seropositive patients with and
      without anti-leucine-rich glioma-inactivated protein 1 (LGI1)/contactin
      associated protein-like 2 (CASPR2) antibodies (Abs). METHODS: We performed a
      retrospective analysis of 50 anti-VGKC-complex seropositive patients from January
      2013 to September 2016, and tested them for anti-LGI1/CASPR2 Abs. Comparative
      analysis was performed between anti-LGI1/CASPR2 seropositive and 'double
      negative' patients. RESULTS: Seven patients had anti-LGI1/CASPR2 Abs while 43
      patients were 'double negative' for these 2 Abs. Three 'double negative' patients
      had other neuronal surface Abs and were excluded from analysis. Compared to
      'double negative' patients, a higher proportion of anti-LGI1/CASPR2 seropositive
      patients had complex partial seizures (5/7 vs 5/40; p = .003), limbic
      encephalitis (4/7 vs 2/40; p = .003), hippocampal imaging abnormalities (5/7 vs
      3/39; p < .001), temporal epileptiform activity/electrographic seizures (4/6 vs
      4/27; p = .020), tumours (3/7 vs 0/40; p = .002), and received acute
      immunotherapy (5/7 vs 6/40; p = .005) and maintenance immunotherapy (5/7 vs 4/40;
      p = .001). Anti-LGI1/CASPR2 seropositive patients had higher anti-VGKC-complex
      Abs levels (median 2857 pM [range 933-6730] vs 165 pM [104-1065]; p < .001). In
      contrast, a higher proportion of 'double negative' patients had non-specific
      behavioral disorders (20/40 vs 0/7; p = .015), and 13 of 40 (32.5%) had
      alternative organic diagnoses. CONCLUSION: In anti-VGKC-complex seropositive
      patients, we identified features in patients with anti-LGI1/CASPR2 Abs distinct
      from 'double negative' patients, and found that 'double negative' patients were
      associated with non-specific clinical features and had a high rate of alternative
      diagnosis. These findings demonstrate the limited utility of anti-VGKC-complex
      Abs testing in suspected neurological autoimmunity.

PMID- 30103976
TI  - A new scale measuring adaptive perceived control for people with Parkinson's:
      Initial construction and further validation.
AB  - INTRODUCTION: Perceived control is an important concept in understanding
      adjustment to chronic conditions such as Parkinson's. While generic measures have
      been used to measure the construct in Parkinson's, no Parkinson's-specific scale
      currently exists. This study outlines the initial development and further
      validation of a free-to-use scale, the Parkinson's UK Scale of Perceived Control
      (PUKSoPC). METHOD: Focus groups were used to create items for the new scale.
      Potential items were then subject to screening for readability and coherence by
      people affected by the condition. This left 49 items that were then completed,
      along with other measures, by 231 people with Parkinson's. Exploratory factor
      analysis then created a 15-item scale with five distinct subscales. This initial
      structure was then further tested using confirmatory factor analysis with 2032
      people with Parkinson's. Structural equation modelling confirmed the
      acceptability of the total scale and subscale structures. RESULTS: The final
      scale is concluded to be a psychometrically robust measure of perceived control.
      It has good face validity, evidence of convergent and criterion (concurrent and
      divergent) validity, good test-retest reliability and is internally coherent,
      with a demonstrably solid factor structure. While further testing would be useful
      to assess the scale's predictive ability, it is currently considered robust
      enough for more widespread use. CONCLUSION: The PUKSoPC is an appropriate scale
      to provide a more comprehensive measure of perceived control. It is preferable to
      single item, non-validated measures and can provide evidence of perceptions of
      control across a number of domains important in the measurement of the construct.

PMID- 30103975
TI  - Predictors of relapse and disability progression in MS patients who discontinue
      disease-modifying therapy.
AB  - BACKGROUND: Discontinuation of disease-modifying therapies (DMTs) for MS is
      common. MSBase, a large global observational registry, affords a unique
      opportunity to investigate predictors of 'post-DMT' relapses and confirmed
      disability progression (CDP) in a diverse group of patients exposed to different
      DMTs. MATERIALS/METHODS: Main inclusion criteria: clinician-confirmed MS
      diagnosis (2010 McDonald criteria); age >= 18 at index DMT start; >=12 months on
      index DMT prior to discontinuation; >=24 months of follow-up post
      discontinuation; did not restart DMT for >=6 months. Predictors of time to first
      relapse and 3-month CDP were analyzed using Cox proportional hazards regression
      adjusted for age, gender, baseline EDSS, EDSS stability and relapse-free period
      for >=1 year prior to discontinuation, calendar epoch, index DMT and reason for
      discontinuation. RESULTS: 4842 patients (74.2% female) from 20 MSBase Centers met
      our inclusion criteria. 3556 (73%) discontinued one of IFNbeta preparations, 849
      (18%) - glatiramer acetate, 308 (6%) - natalizumab and 129 (3%) - fingolimod;
      other DMTs were excluded because too few records were available. Overall post
      discontinuation annualized relapse rate (95% CI) was 0.224 (0.219, 0.229) and CDP
      rate was 8.23 (7.72, 8.76) per 100 person-years. Risk of post-DMT relapse was
      higher in younger patients, female patients, those with moderate disability and a
      relapse within 1 year of discontinuation. Hazard of CDP increased with increasing
      disability at baseline and disease progression within 3 years prior to stopping
      DMT. Of all the DMTs, only natalizumab was associated with increased risk of both
      post-DMT relapse and CDP. CONCLUSIONS: Knowledge of post-DMT relapse and
      disability progression rates and predictors of post-DMT disease activity allows
      for a more informed discussion of DMT discontinuation in those patients who are
      considering this option.

PMID- 30103977
TI  - Vitamin D receptor (VDR) gene polymorphism and vascular dementia due to cerebral
      small vessel disease in an Asian Indian cohort.
AB  - Vitamin D receptor (VDR) and its ligand Vitamin D, play a crucial role in
      regulating multiple pathways for maintaining vascular health. The present study
      aimed at evaluating whether single nucleotide polymorphisms in VDR gene were
      associated with susceptibility to vascular dementia (VaD) due to cerebral small
      vessel disease (SVD). A total of 644 subjects (302 patients diagnosed with
      cerebral SVD-associated VaD and 342, age- and gender-matched healthy controls)
      were genotyped for VDR gene variants, FokI, ApaI, TaqI and BsmI, by PCR-RFLP
      method. Among the 4 examined VDR variants, the presence of the minor allele
      (Ff+ff vs FF) of FokI variant increased the risk for cerebral SVD by 1.5-fold in
      men (p = 0.047). Serum 25-hydroxyvitamin D [25(OH)D] was lower in subjects having
      the FokI "ff" genotype compared to those with the "FF" genotype (p = 0.044).
      Moreover, in subjects with low serum 25(OH)D the presence of "ff" genotype
      increased the odds of SVD by 2.5 folds (p = 0.041). ApaI polymorphism decreased
      the risk of cerebral SVD in women. The distribution of TaqI and BsmI variants
      were not significantly different between patients and controls. Further studies
      in large cohorts are necessary to validate the role of FokI polymorphism in
      cerebral SVD and VaD etiopathogenesis.

PMID- 30103978
TI  - Tau clearance improves astrocytic function and brain glutamate-glutamine cycle.
AB  - Tau hyperphosphorylation is a critical factor in neurodegenerative diseases,
      including dementia and Parkinsonism. Existing animal models of tauopathies
      express tau in neurons within the forebrain and do not often show tau
      accumulation in the brainstem and astrocytes. This study aims to understand the
      effects of differential regional expression of tau on neurotransmitter balance in
      the brain. To obtain an animal model that expresses tau in the brainstem, we bred
      hemizygous mice that express P301L tau (TauP301L) and detected hyper
      phosphorylated tau (p-tau) predominantly in the hippocampus, cortex, brainstem
      and thalamus. We previously demonstrated that TauP301L mice [26] express tau
      under the control of a prion promoter in both neurons and astrocytes, reminiscent
      of human tauopathies. We treated TauP301L mice with tyrosine kinase inhibitors
      (TKIs) to determine the effects of tau clearance on neurotransmitter balance and
      astrocytic function. 13C/1H MRS reveals astrocytic dysfunction via reduced glial
      aspartate and impaired glutamate-glutamine cycle. An increase in glutamate and
      GABA and decrease in glutamine were observed in homozygous mice compared to
      hemizygous and control littermates. Daily treatment with TKIs, nilotinib or
      bosutinib led to p-tau clearance via autophagy and reversal of neurotransmitter
      imbalance. These data suggest that accumulation of p-tau in the brainstem does
      not alter dopamine metabolism but may trigger glutamate toxicity and astrocytic
      dysfunction in the TauP301L mouse. TKIs reverse tau effects via reversal of
      neurotransmitter imbalance.

PMID- 30103979
TI  - Prescribing patterns of evidence-based heart failure pharmacotherapy and outcomes
      in the ASIAN-HF registry: a cohort study.
AB  - BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors or angiotensin II
      receptor blockers (ARBs), beta blockers, and mineralocorticoid receptor
      antagonists (MRAs) are of proven benefit and are recommended by guidelines for
      management of patients with heart failure and reduced ejection fraction (HFrEF).
      We aimed to examine the first prospective multinational data from Asia on
      prescribing patterns of guideline-directed medical therapies and analyse its
      effect on outcomes. METHODS: In the prospective multinational ASIAN-HF registry
      (with enrolment from 46 centres in 11 countries in Asia), we enrolled patients
      aged 18 years or older, with symptomatic heart failure (stage C, with at least
      one episode of decompensated heart failure in the past 6 months that resulted in
      admission to hospital or was treated in an outpatient clinic) and left
      ventricular systolic dysfunction (ejection fraction <=40% on baseline
      echocardiography, consistent with 2016 European Society of Cardiology
      guidelines). We excluded patients with heart failure caused by severe valvular
      heart disease, life-threatening comorbidity with a life expectancy of less than 1
      year, who were unable or unwilling to give consent, or who had concurrent
      participation in a clinical trial. Patients were followed up for 3 years for the
      outcomes of death and cause-specific admittance to hospital. Primary outcomes
      were uptake of guideline-directed medical therapies (as proportions) by
      therapeutic class, achieved doses as proportions of guideline-recommended doses,
      and their association with 1-year composite outcome of all-cause death or
      admittance to hospital because of heart failure. This study is registered with
      ClinicalTrials.gov, number NCT01633398. FINDINGS: Between Oct 1, 2012, and Dec
      31, 2015, we enrolled 5276 patients with HFrEF (mean age 59.6 years [SD 13.2],
      77% men, body-mass index 24.9 kg/m2 [5.1], 33% New York Heart Association class
      III or IV). Follow-up data were available for 4544 (90%) of 5061 eligible
      patients taking medication for heart failure, with median follow-up of 417 days
      (IQR 214-735). ACE inhibitors or ARBs were prescribed to 3868 (77%) of 5005
      patients, beta blockers to 3975 (79%) of 5061, and MRAs to 2998 (58%) of 5205,
      with substantial regional variation. Guideline-recommended dose was achieved in
      only 17% of cases for ACE inhibitors or ARB, 13% for beta blockers, and 29% for
      MRAs. Country (all three drug classes), increasing body-mass index (ACE
      inhibitors or ARBs and MRAs), and in-patient recruitment (ACE inhibitors or ARBs
      and beta blockers) were associated with attainment of guideline-recommended dose
      (all p<0.05). When adjusted for indication bias, increasing drug doses, from low
      dose (1-<25% of guideline-recommended dose) upwards were associated with lower
      hazards of a 1-year composite outcome for ACE inhibitors or ARBs and beta
      blockers compared with non-users. The lowest adjusted hazards were in the group
      that attained guideline-recommended doses above 50% (hazard ratio [HR] 0.54, 95%
      CI 0.50-0.58 for ACE inhibitors or ARBs [50-99.9%]; HR 0.47, 0.46-0.50 for beta
      blockers, and HR 0.77, 0.72-0.81 for MRAs [>=100%]). INTERPRETATION: Guideline
      directed medical therapies at recommended doses are underutilised in patients
      with HFrEF. Improved uptake and uptitration of guideline-directed medical
      therapies are needed for better patient outcomes. FUNDING: National Medical
      Research Council (Singapore), A*STAR Biomedical Research Council ATTRaCT program,
      Boston Scientific Investigator Sponsored Research program, and Bayer.

PMID- 30103982
TI  - Getting to the heart of non-communicable diseases.

PMID- 30103983
TI  - Estimating the impact of antimicrobial resistance.

PMID- 30103980
TI  - Long-term effectiveness of one and two doses of a killed, bivalent, whole-cell
      oral cholera vaccine in Haiti: an extended case-control study.
AB  - BACKGROUND: No study of long-term protection following killed oral cholera
      vaccination has been done outside of the historically cholera-endemic areas of
      south Asia, or has examined protection after a single-dose vaccination regimen.
      To address this, we examined the duration of protection of the standard two-dose
      regimen and an incomplete regimen of one dose up to 4 years after vaccination in
      Haiti. METHODS: In the setting of two-dose vaccination campaigns with a killed,
      bivalent, whole-cell oral cholera vaccination, we did a case-control study from
      October, 2012 through November, 2016. Eligible participants were required to be
      resident in the vaccine catchment area (Artibonite Department or Central
      Department) where they were recruited at the start of the study; and be eligible
      for the vaccination campaign (ie, aged >=12 months, not pregnant, and living in
      the region at the time of the vaccine campaign). Patients with cholera had a
      positive stool culture and were recruited from cholera treatment centres.
      Community controls were matched to people with cholera by age group, time, and
      neighbourhood. We did adjusted matched regression analyses to calculate vaccine
      effectiveness and examine heterogeneity in effectiveness over time. The primary
      outcome was the effectiveness of one and two oral cholera doses as compared with
      zero doses from 2 months to 48 months after vaccination, measured by self
      reporting. FINDINGS: Among 178 people assigned to the case group and 706 people
      assigned to the control group, we found no evidence that two-dose effectiveness
      decreased during follow-up. In adjusted analyses, the average cumulative 4 year
      effectiveness for two doses was 76% (95% CI 59-86). In contrast, single-dose
      effectiveness decreased over time in a log-linear fashion, with a predicted
      vaccine effectiveness of 79% at the end of 12 months (95% CI 43-93), which
      declined to zero before the end of the second year. INTERPRETATION: In a setting
      of epidemic and newly endemic cholera in Haiti, single-dose vaccination with
      killed, bivalent, whole-cell oral cholera vaccination provided short-term
      protection; however, vaccination with two doses was required for long-term
      protection, which lasted up to 4 years after vaccination. These results add to
      the evidence in support of the use of killed, bivalent, whole-cell oral cholera
      vaccination as part of comprehensive cholera control plans. FUNDING: US National
      Institute of Allergy and Infectious Diseases of the National Institutes of Health
      and the Bill & Melinda Gates Foundation.

PMID- 30103984
TI  - Dyslipidaemia among African adults.

PMID- 30103981
TI  - Impact of monovalent rotavirus vaccine on diarrhoea-associated post-neonatal
      infant mortality in rural communities in Malawi: a population-based birth cohort
      study.
AB  - BACKGROUND: Rotavirus is a major contributor to child mortality. The effect of
      rotavirus vaccine on diarrhoea mortality has been estimated in middle-income but
      not low-income settings, where mortality is high and vaccine effectiveness in
      reducing admissions to hospital is lower. Empirical population-based mortality
      studies have not been done in any setting. Malawi introduced monovalent rotavirus
      vaccine (RV1) in October, 2012. We aimed to investigate the impact and
      effectiveness of the RV1 vaccine in reducing diarrhoea-associated mortality in
      infants aged 10-51 weeks. METHODS: In this population-based cohort study, we
      included infants born between Jan 1, 2012, and June 1, 2015, in Mchinji, Central
      Malawi and analysed data on those surviving 10 weeks. Individual vaccination
      status was extracted from caregiver-held records or report at home visits at 4
      months and 1 year of age. Survival to 1 year was confirmed at home visit, or
      cause of death ascertained by verbal autopsy. We assessed impact (1 minus
      mortality rate ratio following vs before vaccine introduction) using Poisson
      regression. Among vaccine-eligible infants (born from Sept 17, 2012), we assessed
      effectiveness (1 minus hazard ratio) using Cox regression. FINDINGS: Between Jan
      1, 2012, and June 1, 2015, we recruited 48 672 livebirths in Mchinji, among whom
      38 518 were vaccine-eligible and 37 570 survived to age 10 weeks. Two-dose versus
      zero-dose effectiveness analysis included 28 141 infants, of whom 101 had
      diarrhoea-associated death before 1 year of age. Diarrhoea-associated mortality
      declined by 31% (95% CI 1-52; p=0.04) after RV1 introduction. Effectiveness
      against diarrhoea-mortality was 34% (95% CI -28 to 66; p=0.22). INTERPRETATION:
      RV1 was associated with substantial reduction in diarrhoea-associated deaths
      among infants in this rural sub-Saharan African setting. These data add
      considerable weight to evidence showing the impact of rotavirus vaccine
      programmes. FUNDING: Wellcome Trust and GlaxoSmithKline Biologicals.

PMID- 30103985
TI  - Medical therapy for heart failure: the evidence exists, but is it being followed?

PMID- 30103986
TI  - Protection from killed oral cholera vaccine continues for 4 years.

PMID- 30103987
TI  - Rotavirus vaccine impact in Africa: greater than the sum of its parts?

PMID- 30103989
TI  - Effective cross-sector collaborations create sustainability.

PMID- 30103988
TI  - Podoconiosis research to implementation: a call for global action.

PMID- 30103990
TI  - Mental health in Africa.

PMID- 30103991
TI  - Clinical research networks are key to accurate and timely assessment of pandemic
      clinical severity.

PMID- 30103992
TI  - Health effects of mass-media interventions.

PMID- 30103993
TI  - Health effects of mass-media interventions - Author's reply.

PMID- 30103994
TI  - Lymphoedema management in podoconiosis.

PMID- 30103995
TI  - Lymphoedema management in podoconiosis - Authors reply.

PMID- 30103996
TI  - Parasitic and parachute research in global health.

PMID- 30103997
TI  - Secondary analysis and participation of those at the data source.

PMID- 30103998
TI  - Estimating the number of infections caused by antibiotic-resistant Escherichia
      coli and Klebsiella pneumoniae in 2014: a modelling study.
AB  - BACKGROUND: The number of infections caused by resistant organisms is largely
      unknown. We estimated the number of infections worldwide that are caused by the
      WHO priority pathogens third-generation cephalosporin-resistant and carbapenem
      resistant Escherichia coli and Klebsiella pneumoniae. METHODS: We calculated a
      uniform weighted mean incidence of serious infections caused by antibiotic
      susceptible E coli and K pneumoniae using data from 17 countries. Using this
      uniform incidence, as well as population sizes and country-specific resistance
      levels, we estimated the number of infections caused by third-generation
      cephalosporin-resistant and carbapenem-resistant E coli and K pneumoniae in 193
      countries in 2014. We also calculated interval estimates derived from changing
      the fixed incidence of susceptible infections to 1 SD below and above the
      weighted mean. We compared an additive model with combination models in which
      resistant infections were replaced by susceptible infections. We distinguished
      between higher-certainty regions (those with good-quality data sources for
      resistance levels and resistance <=30%), moderate-certainty regions (those with
      good-quality data sources for resistance levels and including some countries with
      resistance >30%), and low-certainty regions (those in which good-quality data
      sources for resistance levels were unavailable for countries comprising at least
      20% of the region's population, regardless of resistance level). FINDINGS: Using
      the additive model, we estimated that third-generation cephalosporin-resistant E
      coli and K pneumoniae caused 6.4 million (interval estimate 3.5-9.2) bloodstream
      infections and 50.1 million (27.5-72.8) serious infections in 2014; estimates
      were 5.5 million (3.0-7.9) bloodstream infections and 43.1 million (23.6-62.2)
      serious infections in the 25% replacement model, 4.6 million (2.5-6.6)
      bloodstream infections and 36.0 million (19.7-52.2) serious infections in the 50%
      replacement model, and 3.7 million (2.0-5.3) bloodstream infections and 28.9
      million (15.8-41.9) serious infections in the 75% replacement model. Carbapenem
      resistant strains caused 0.5 million (0.3-0.7) bloodstream infections and 3.1
      million (1.8-4.5) serious infections based on the additive model, 0.5 million
      (0.3-0.7) bloodstream infections and 3.0 million (1.7-4.3) serious infections
      based on the 25% replacement model, 0.4 million (0.2-0.6) bloodstream infections
      and 2.8 million (1.6-4.1) serious infections based on the 50% replacement model,
      and 0.4 million (0.2-0.6) bloodstream infections and 2.7 million (1.5-3.8)
      serious infections based on the 75% replacement model. INTERPRETATION: To our
      knowledge, this study is the first to report estimates of the global number of
      infections caused by antibiotic-resistant priority pathogens. Uncertainty stems
      from scant data on resistance levels from low-income and middle-income countries
      and insufficient knowledge regarding resistance dynamics when resistance is high.
      FUNDING: Innovative Medicines Initiative.

PMID- 30104001
TI  - Diagnosis of lung tumor types based on metabolomic profiles in lymph node
      aspirates.
AB  - BACKGROUND: Treatment of lung cancer is evolving from the use of cytotoxic drugs
      to drugs that interrupt pathways specific to a malignancy. The field of
      metabolomics has promise with respect to identification of tumor-specific
      processes and therapeutic targets, but to date has yielded inconsistent data in
      patients with lung cancer. Lymph nodes are often aspirated in the process of
      evaluating lung cancer, as malignant cells in lymph nodes are used for diagnosis
      and staging. We hypothesized that fluids from lymph node aspirates contains tumor
      specific metabolites and are a suitable source for defining the metabolomic
      phenotype of lung cancers. PATIENTS AND MATERIALS: Metabolic profiles were
      generated from nodal aspirates of ten patients with adenocarcinoma, ten with
      squamous cell carcinoma, and ten with non-malignant conditions using time-of
      flight mass spectrometry. In addition, concentrations of selected metabolites
      participating in the kynurenine and glutathione pathways were measured in a
      second set of aspirates using tandem mass spectrometry. RESULTS: A list of
      consensus features that separated these three groups was identified. Two of the
      consensus features were tentatively identified as kynurenine and as oxidized
      glutathione. It was shown that metabolite concentrations in these pathways are
      different for patients with and without malignancy. CONCLUSION: Together the data
      suggest that metabolomic analysis of lymph node aspirates can identify tumor
      specific differences in cancer metabolism and reveal novel therapeutic targets.
      This proof-of-concept study demonstrates the validity to complement and refine
      diagnosis of lung cancer based on metabolic signature in lymph node aspirates.
      MICRO ABSTRACT: Treatment of lung cancer is evolving from the use of cytotoxic
      drugs to drugs that interrupt metabolic pathways specific to a malignancy. We
      report here in that the metabolic phenotype of lung cancer can be determined in
      lymph node aspirates harboring malignant tumor cells. Knowledge about metabolic
      activity of malignant tumor cells may aide to personalize therapy.

PMID- 30103999
TI  - Prevalence of dyslipidaemia among adults in Africa: a systematic review and meta
      analysis.
AB  - BACKGROUND: The burden of dyslipidaemia in Africa remains inadequately
      characterised. We aimed to estimate the prevalence of dyslipidaemia in African
      adults from hospital-based and community-based studies. METHODS: In this
      systematic review and meta-analysis, we searched MEDLINE via PubMed, Embase,
      African Journals Online, and African Index Medicus for studies published between
      Jan 1, 1980, and July 31, 2017, without language restriction. We assessed
      methodological quality of all cross-sectional studies reporting on the prevalence
      of elevated concentrations of total cholesterol, LDL cholesterol, or
      triglycerides, or low concentrations of HDL cholesterol in adults residing in
      African countries. We excluded reports on Africans living outside Africa, studies
      of individuals selected on the basis of existing dyslipidaemia or those including
      children and adolescents, and case series with a small sample size. The most
      frequently used cutoffs in the included studies were chosen for the subgroup
      analysis. We used random-effect model meta-analysis to derive the pooled
      prevalence of elevated total cholesterol, low HDL cholesterol, elevated LDL
      cholesterol, and elevated triglyceride concentrations. This study is registered
      with PROSPERO, number CRD42014015376. FINDINGS: 181 studies (309 207
      participants) were included in the meta-analysis. The pooled prevalence of
      dyslipidaemia in the general population from population-based studies was 23.6%
      (95% CI 18.4-29.2) for elevated concentrations of total cholesterol with a cutoff
      of at least 5.2 mmol/L, 41.1% (33.0-49.4) for low concentrations of HDL
      cholesterol with a cutoff of less than 1.0 mmol/L, 25.7% (16.2-36.6) for elevated
      concentrations of LDL cholesterol with a cutoff of at least 3.3 mmol/L, and 16.5%
      (11.8-21.6) for elevated concentrations of triglycerides with a cutoff of at
      least 1.7 mmol/L. INTERPRETATION: The prevalence of dyslipidaemia is high in the
      general adult population in Africa. Ongoing efforts to reduce cardiovascular
      diseases in Africa should integrate effective detection and treatment of
      dyslipidaemia. FUNDING: None.

PMID- 30104002
TI  - Association of ER-alpha gene PvuII polymorphism with ovarian cancer.
AB  - BACKGROUND: Ovarian cancer is the most common cancer among women worldwide.
      Estrogen plays an important role in follicle formation and maturation of oocyte
      via its receptor (ER). It has a special interest as their protein levels are
      always elevated in premalignant and malignant cancer cells and are over expressed
      in different tumors with a favourable prognosis. The present study is aimed to
      evaluate the role of ER-alpha gene ( rs2234693) PVUII polymorphism in the
      etiology of ovarian cancer. MATERIALS AND METHODS: A total of eighty clinically
      and histopathologically confirmed ovarian cancer patients and 100 healthy control
      subjects were included in the present study. Demographic details along with blood
      samples were collected from all the subjects. DNA was extracted, amplified and
      genotyped for ER-alpha gene PVUII polymorphism by PCR-RFLP method followed by
      agarose gel electrophoresis. Statistical methods were applied to test for the
      significance of the results. RESULTS: The genotype frequencies revealed 50% of
      wild homozygotes (PP), 33.75% of heterozygotes (Pp), 16.25% of mutant homozygotes
      (pp) in the diseased group and 79% of wild homozygotes (PP), 12% of heterozygotes
      (Pp), 9% of mutant homozygotes (pp) in the control group. There is a significant
      increase of p allele in patients compared to controls. CONCLUSION: The present
      study thus indicates the possible association of PVUII polymorphism of ER-alpha
      gene in the etiology of ovarian cancer.

PMID- 30104003
TI  - Ductal carcinoma in situ of the breast - Long term results from a twenty-year
      cohort.
AB  - INTRODUCTION: Long-term survival is excellent in ductal Carcinoma in situ (DCIS);
      whether or not we are over-treating DCIS has been a major public concern. This
      study aims at reviewing the long-term survival outcome of DCIS and identifying
      adverse prognosticators for DCIS. PATIENTS AND METHODS: Patients treated for DCIS
      between 1st January 1997 and 31st December 2016 were identified from a
      prospectively maintained database. Multivariate analysis was performed to
      evaluate the adverse factors for surgical margin involvement and local recurrence
      RESULTS: 3042 female patients were treated for breast cancer over the 20-year
      study period, of which 203 (6.7%) had DCIS in final pathology. The median age of
      diagnosis was 53 year-old (Range 30-85). 57 (28.1%) were detected by screening
      mammogram, 101 had breast mass on presentation. 132 (65%) patients received
      mastectomy and the remaining received breast conserving surgery (BCS); Sentinel
      lymph node biopsy was performed in 86 (42.4%) patients. 19 (9.4%) patients had
      positive resection margin, 18 were re-operated for clear resection margin.
      Multivariate analysis found that high grade DCIS is the only independent risk
      factors for margin involvement (HR 2.55, 95% CI 1.02-6.42). After median follow
      up of 106 months (6-223 months), the overall survival was 97%. 4 (2%) patients
      developed local recurrence. Multivariate analysis found that positive surgical
      margin is the only independent factor of local recurrence (HR 9.58, 95% CI 1.43
      64.18). CONCLUSION: High grade DCIS is associated with increased risk of surgical
      margin involvement which is in turn an independent factor of local recurrence.

PMID- 30104004
TI  - Is it reasonable to administer pegfilgrastim on day 1 of a myelosuppressive
      chemotherapy regimen? A cost-utility analysis.
AB  - BACKGROUND: There is recent evidence supporting the safety and efficacy of same
      day dosing of pegfilgrastim in patients undergoing chemotherapy. OBJECTIVE: To
      determine the cost-effectiveness of pegfilgrastim on day 1 (D1) versus day 2 (D2)
      for primary prevention of neutropenia in women receiving chemotherapy. MATERIALS
      AND METHODS: A cost-utility model was designed comparing standard D2 versus D1
      administration of pegfilgrastim to ovarian cancer patients receiving chemotherapy
      with an intermediate risk (10-15%) of febrile neutropenia (FN). Rates of FN
      despite prophylaxis were modeled as 10% for D1 and 5% for D2. Societal costs
      associated with D2 injection ($175.71) were incorporated. Quality of life (QOL)
      was modeled from published data; we assumed a small decrement in QOL on treatment
      days. Sensitivity analyses were performed. RESULTS: D1 administration was less
      costly ($17,195 versus $17,681) and resulted in higher QOL (0.2298 quality
      adjusted life years (QALYs) versus 0.2288 QALYs) than D2. Results were sensitive
      to the risk of FN. D1 remained dominant or cost-effective (ICER less than
      $50,000/QALY) compared to D2 if the FN rate with D1 was assumed less than 14.5%
      (baseline estimate 10%). If the FN rate with D1 was assumed greater than or equal
      to 15%, D1 was not cost-effective compared to D2, with an ICER greater than
      $100,000/QALY. Findings are insensitive to variations in the modeled cost of
      treating FN, the additional cost of D2 injection, and the reduced QOL associated
      with treatment visits. CONCLUSION: Administration of D1 pegfilgrastim is cost
      effective in women with ovarian cancer who are treated with intermediate risk
      chemotherapy.

PMID- 30104005
TI  - Comparison of endometriotic cysts and ovarian cancer in association with
      endometriotic cysts.
AB  - OBJECTIVE: The aim of this study was to clarify the clinical, laboratory, and
      imaging findings of ovarian cancer in association with endometriotic cysts by
      detailed comparison of the findings of benign and malignant tumors. METHODS AND
      MATERIALS: This was a retrospective study of 138 women who had an operation for
      ovarian tumors at the Department of Obstetrics and Gynecology of Kochi Health
      Sciences Center between September 1, 2011, and July 30, 2015. The ovarian tumors
      were divided into two groups: the benign group (endometriotic cysts) and the
      malignant group (ovarian cancer in association with endometriotic cysts).
      RESULTS: Of the 138 patients, 28 had malignant disease, and 110 had benign
      endometriotic cysts. Patients in the malignant group were significantly older
      than patients in the benign group. The mean maximum tumor diameter was also
      significantly larger for the malignant tumors. Unilocular-solid and multilocular
      solid type tumors were present in 25.0% and 75.0% of malignant tumors, and in
      9.1% and 19.1% of benign tumors, respectively. The mean maximum solid component
      diameter and height were significantly larger in the malignant tumors than in the
      benign tumors. The solid components were present on the abdominal side of the
      cyst wall in 12.5% of benign tumors and in 51.9% of malignant tumors. CONCLUSION:
      In elderly patients, the presence of large solid components in large
      endometriotic cysts, especially the abdominal side of the cyst wall, might
      suggest malignancy. MICRO ABSTRACT: The aim of this study was to clarify the
      findings of ovarian cancer in association with endometriotic cysts by detailed
      comparison of the findings of benign and malignant tumors. The presence of solid
      components in large endometriotic cysts, especially the abdominal side of the
      cyst wall, might suggest malignancy.

PMID- 30104006
TI  - Comparative assessment of late toxicity in patients of carcinoma cervix treated
      by radiotherapy versus chemo-radiotherapy - Minimum 5 years follow up.
AB  - BACKGROUND: A randomised trial was carried out comparing chemo-radiation (CTRT)
      vs. radiotherapy (RT) in patients of carcinoma cervix and showed similar rates of
      pelvic disease control, disease free survival and overall survival. Late toxicity
      is presented. METHODS: Between December 2000 and July 2006, 180 patients of
      carcinoma cervix were randomly assigned to RT + weekly cisplatin (n = 94) or RT
      alone (n = 86). Late toxicity was prospectively scored using RTOG criteria in 156
      evaluable patients, 79 and 77 respectively and is presented as crude incidence
      for rectum, bladder, small intestine, vagina, skin and bone and also as actuarial
      incidence for rectum and bladder. RESULTS: The median follow up of surviving
      patients was 10.4 years (minimum - 6.5 years). Crude incidence, CTRT vs. RT, of
      late toxicities were: rectal (7.5% vs. 5%, p = 0.22), bladder (15% vs. 10.4%, p =
      0.76), small bowel (3% vs. 1.2%, p = 0.51), vagina (25% vs. 35%, p = 0.35) while
      the actuarial risk of grades 3-5 rectal and bladder toxicities by 5 years were
      13% vs. 10% (p = 0.698) and 16% vs. 14.8% (p = 0.783) respectively. Bladder
      toxicity appeared later then rectal toxicity (median 49.4 vs. 21.4 months).
      Severe bone toxicity (fractures) were higher in the CTRT arm, 5% vs. 0%, p =
      0.018. On multivariate analysis vaginal involvement (p = 0.016) and bulky tumor
      (p = 0.020) were associated with severe vaginal morbidity while rectal point dose
      > 80% (p = 0.040) was associated with a higher incidence of rectal toxicity.
      CONCLUSION: Bone toxicity was significantly increased by addition of CT to RT and
      patients continued to experience toxicity at longer periods of follow up albeit
      disease free.

PMID- 30104007
TI  - Veliparib and topotecan for patients with platinum-resistant or partially
      platinum-sensitive relapse of epithelial ovarian cancer with BRCA negative or
      unknown BRCA status.

PMID- 30104008
TI  - A cost-effectiveness analysis of consolidative local therapy in oligometastatic
      non-squamous non-small cell lung cancer (NSCLC).
AB  - BACKGROUND: Novel systemic therapies have improved the prognosis of metastatic
      non-small cell lung cancer (NSCLC), but costs of some of these drugs are a matter
      of ongoing debate. More recently, local therapies (LT) such as radiotherapy and
      surgery have been suggested as additional treatment in oligometastatic NSCLC
      demonstrating an improved progression-free survival (PFS) in a phase II trial
      compared to maintenance chemotherapy (MC) alone. The aim of this analysis was to
      assess the cost-effectiveness of local therapies in oligometastatic NSCLC.
      METHODS: We constructed a Markov model comparing the cost-effectiveness of LT
      versus MC for oligometastatic NSCLC from the Swiss healthcare payer's
      perspective. Treatment specifications and PFS were based on the phase II trial
      (NCT01725165). Overall survival (OS) was inferred from a recent phase III trial.
      Utilities were taken from published data. Primary outcome was the incremental
      cost-effectiveness-ratio (ICER, costs in Swiss Francs (CHF) per quality-adjusted
      life-year (QALY) gained). RESULTS: PFS in the model was 3.8 months for MC and
      11.4 months for LT (compared to 3.9 months and 11.9 months in the trial). OS in
      the model was 15.5 months in both arms. LT was cost-effective with a gain of 0.24
      QALYs at an additional cost of CHF 9641, resulting in an ICER of CHF 40,972/QALY
      gained. Probabilistic sensitivity analyses demonstrated that LT was dominant or
      cost-effective at a willingness-to-pay threshold of CHF 100,000 per QALY in 61.7%
      of the simulations. CONCLUSIONS: LT may be cost-effective for selected patients
      with oligometastatic NSCLC responding to first-line systemic therapy.

PMID- 30104009
TI  - What education, background, and credentials are required to provide genetic
      counseling?
AB  - Technological advances in genetics have resulted in an increase in the number and
      complexity of screening and diagnostic tests in the prenatal clinical arena. It
      is critical that patients are provided with appropriate counseling to enable them
      to make educated decisions. During this workshop session participants discussed
      the education, background and credentials required to provide counseling
      regarding prenatal genetic testing options. The participants agreed that prenatal
      care providers may have limited time and training to adequately address prenatal
      genetic testing. Telemedicine and online education may help to address this
      challenge. Workshop participants agreed that educational and certifying
      organizations should work together to develop standards for the certification and
      maintenance of certification processes.

PMID- 30104010
TI  - Angels and Devils: Dilemmas in Dual-Use Biotechnology.
AB  - Dual-use research, which results in knowledge that can be used for both good and
      ill, has become increasingly accessible in the internet age to both scientists
      and the general public. Here, we outline some major milestones for dual-use
      policy and present three vignettes that highlight contemporary dual-use issues in
      biotechnology.

PMID- 30104011
TI  - We Must Not Avoid Germline Gene Editing to Preserve Social Values: A Response to
      Saha et al.
AB  - A recent paper suggested that although the effects of germline gene editing in
      certain individuals might benefit them, their genomes should not be edited
      because societal interest might be affected. This statement contradicts the idea
      that human beings may never be used as means to an end.

PMID- 30104012
TI  - Pyrolysis of Torrefied Biomass.
AB  - Pyrolysis, one of the most promising thermal conversion technologies for biomass
      conversion, can decompose biomass into solid bio-char, liquid bio-oil, and
      combustible gas to meet different energy needs. However, pyrolysis efficiency and
      product quality are not as good as expected when raw biomass is used owing to the
      properties of raw biomass (e.g., high moisture, oxygen, and alkali metal
      contents). Torrefaction is an emerging biomass pretreatment technology that can
      improve the physical and chemical properties of raw biomass, and pyrolysis
      efficiency and final product quality can therefore be improved by using torrefied
      biomass. We review several advantages of pyrolysis of torrefied biomass in terms
      of the conversion process and final product quality.

PMID- 30104013
TI  - 3D approach visualizing cellular networks in human lymph nodes.
AB  - Lymph node diagnostics are essentially based on cutting thin sections of formalin
      fixed tissues. After hematoxylin and eosin stain, Giemsa stain and
      immunohistochemical staining of these tissues, the lymph node diagnosis is done
      using a light microscope, looking at two-dimensional pictures. Three-dimensional
      visualizations of lymph node tissue have not been used in lymphoma diagnostics
      yet. This article describes three-dimensional visualization of lymphoid tissue,
      using thick paraffin sections, immunostained with monoclonal antibodies, confocal
      laser scanning and data processing with appropriate software and the 3D printing
      process itself. The advantages and disadvantages of different printing techniques
      are discussed as well as the application of 3D models in diagnostics, teaching
      and research of lymph nodes.

PMID- 30104014
TI  - Diagramming Evolution: The Case of Darwin's Trees.
AB  - From his earliest student days through the writing of his last book, Charles
      Darwin drew diagrams. In developing his evolutionary ideas, his preferred form of
      diagram was the tree. An examination of several of Darwin's trees-from sketches
      in a private notebook from the late 1830s through the diagram published in the
      Origin-opens a window onto the role of diagramming in Darwin's scientific
      practice. In his diagrams, Darwin simultaneously represented both observable
      patterns in nature and conjectural narratives of evolutionary history. He then
      brought these natural patterns and narratives into dialogue, allowing him to
      explore whether the narratives could explain the patterns. But Darwin's diagrams
      did not reveal their meaning directly to passive readers; they required readers
      to engage dynamically with them in order to understand the connections they
      disclosed between patterns and narratives. Moreover, the narratives Darwin
      depicted in his diagrams did not represent past sequences of events that he
      claimed had actually occurred; the narratives were conjectural, schematic, and
      probabilistic. Instead of depicting actual histories in all their particularity,
      Darwin depicted narratives in his diagrams in order to make general claims about
      how nature works. The conjunction of these features of Darwin's diagrams is
      central to how they do their epistemic work.

PMID- 30104015
TI  - Rapid degradation and non-selectivity of Dakin's solution prevents effectiveness
      in contaminated musculoskeletal wound models.
AB  - BACKGROUND: Dakin's solution (buffered sodium hypochlorite) has been used as a
      topical adjunct for the treatment of invasive fungal infections in trauma
      patients. Prudent use of Dakin's solution (DS) for complex musculoskeletal wound
      management implies balancing antimicrobial efficacy and human tissue toxicity,
      but little empirical evidence exists to inform clinical practice. To identify
      potentially efficacious DS concentrations and application methods, we conducted
      two animal studies to evaluate the ability of DS to reduce bacterial burden in
      small and large animal models of contaminated musculoskeletal wounds. METHODS: An
      established rat (Rattus norvegicus) contaminated femoral defect model was
      employed to evaluate the antimicrobial efficacy of DS as a topical adjunctive
      treatment for Staphylococcus aureus infection. A range of clinically-relevant DS
      concentrations (0.00025%-0.125%) were tested, both with and without periodic
      replenishment during treatment. Next, an established goat (Capra hircus)
      musculoskeletal wound model, consisting of a Pseudomonas aeruginosa contaminated
      proximal tibia cortical defect, muscle crush, and thermal injury, was utilized to
      evaluate the antimicrobial efficacy of dilute DS (0.0025% and 0.025%) as a
      surgical irrigant solution. In situ reactive chlorine concentrations were
      monitored throughout each treatment using an automated iodometric titration
      approach. RESULTS: In a rat wound model, DS treatment did not significantly
      reduce S. aureus bioburden after 14 days as compared to saline control. Two
      treatment groups (0.01% single application and 0.025% multiple application)
      exhibited significantly higher bacterial burden than control. In a goat
      musculoskeletal wound model, neither 0.0025% nor 0.025% DS significantly altered
      P. aeruginosa bioburden immediately following treatment or at 48 h post
      treatment. Overall, DS applied to exposed soft tissue exhibited rapid
      degradation, e.g., 0.125% DS degraded 32% after 5 s progressing to 86%
      degradation after 15 min following single application. CONCLUSIONS: We did not
      observe evidence of a therapeutic benefit following Dakin's solution treatment
      for any tested concentration or application method in two contaminated
      musculoskeletal wound models. Despite confirmation of robust bactericidal
      activity in vitro, our findings suggest DS at current clinically-used
      concentrations does not kill tissue surface-attached bacteria, nor does it
      necessarily cause host tissue toxicity that exacerbates infection in the setting
      of complex musculoskeletal injury.

PMID- 30104016
TI  - Antiviral Therapies for Herpesviruses: Current Agents and New Directions.
AB  - PURPOSE: The objective of this review was to summarize the recent literature
      describing the current burden of disease due to herpesviruses in the antiviral
      and transplant era; describe mechanisms of action of antiviral agents and the
      development of resistance; summarize the literature of recent antiviral agents
      brought to market as well as agents under development; and to present literature
      on future strategies for herpesvirus therapeutics. METHODS: An extensive search
      of the medical literature related to antiherpesviral therapy was conducted to
      compose this narrative review. Literature searches were performed via PubMed and
      ultimately 137 articles were included as most relevant to the scope of this
      article. FINDINGS: Herpesviruses are a family of DNA viruses that are ubiquitous
      throughout human populations and share the feature of establishing lifelong
      infections in a latent phase with the potential of periodic reactivation. With
      the exception of herpes simplex virus, varicella zoster virus, and Epstein-Barr
      virus, which have a significant disease burden in individuals with normal immune
      function, the morbidity and mortality of the remaining viruses are primarily
      associated with the immunocompromised host. Over the last half-century, several
      agents have been tested in large randomized, placebo-controlled trials that have
      resulted in safe and effective antiviral agents for the treatment of many of
      these infections. IMPLICATIONS: With increasing use of antiherpesviral agents for
      extended periods, particularly in immunocompromised hosts, the emergence of
      resistant viruses has necessitated the development of newer agents with novel
      targets and better side-effect profiles.

PMID- 30104017
TI  - Occurrence of microplastics in raw and treated drinking water.
AB  - The study investigates the content of microplastic particles in freshwater and
      drinking water. Specifically, three water treatment plants (WTPs) supplied by
      different kinds of water bodies were selected and their raw and treated water was
      analysed for microplastics (MPs). Microplastics were found in all water samples
      and their average abundance ranged from 1473 +/- 34 to 3605 +/- 497 particles L-1
      in raw water and from 338 +/- 76 to 628 +/- 28 particles L-1 in treated water,
      depending on the WTP. This study is one of very few that determine microplastics
      down to the size of 1 MUm, while MPs smaller than 10 MUm were the most plentiful
      in both raw and treated water samples, accounting for up to 95%. Further, MPs
      were divided into three categories according to their shape. Fragments clearly
      prevailed at two of the WTPs and fibres together with fragments predominated at
      one case. Despite 12 different materials forming the microplastics being
      identified, the majority of the MPs (>70%) comprised of PET (polyethylene
      terephthalate), PP (polypropylene) and PE (polyethylene). This study contributes
      to fill the knowledge gap in the field of emerging microplastic pollution of
      drinking water and water sources, which is of concern due to the potential
      exposure of microplastics to humans.

PMID- 30104018
TI  - [Hydrochlorothiazide appears to increase risk of melanoma].

PMID- 30104019
TI  - [Prurigo pigmentosa during pregnancy].
AB  - INTRODUCTION: Prurigo pigmentosa is a rare inflammatory dermatosis characterized
      by pruritic and reticulate papules on the trunk leaving hyperpigmentation. This
      dermatosis has been rarely described outside Asia. The pathophysiology remains
      obscure. CASE REPORT: We report the case of a 21-year-old North-African woman
      presenting with a highly pruritic eruption with numerous erythematous macules and
      papules coalescing in a reticular pattern on the trunk. The eruption occurred
      during the first trimester of pregnancy, which was marked by severe vomiting
      resulting in weight loss of 13kg with ketonemia and ketonuria. Taking into
      account the characteristic pattern of the eruption, the absence of differential
      diagnosis, and the histological examination, we concluded on a diagnosis of
      prurigo pigmentosa. Progression of the disease exhibited phases of decreased
      inflammation and of pruritus alternating with episodes of inflammatory flares
      triggered by relapses of ketonemia. The symptoms finally resolved during the 2nd
      trimester of pregnancy after vomiting ceased. Secondary reticulated
      hyperpigmentation was observed. CONCLUSION: Although rare, the highly evocative
      clinical presentation of the eruption should help clinicians in diagnosing
      prurigo pigmentosa. While pathophysiology remains undetermined, prurigo
      pigmentosa was reported in cases of intense fasting, anorexia, type-1 diabetes,
      and in two other cases of pregnancy with severe vomiting. Our case underlines the
      need to screen for and treat underlying ketonemia to achieve control of the
      inflammatory flares of prurigo pigmentosa.

PMID- 30104020
TI  - Pediatric Catatonia: A Case Series-Based Review of Presentation, Evaluation, and
      Management.
AB  - BACKGROUND: Pediatric catatonia is believed to be a rare condition, but
      challenges in recognition and variability in presentation may lead to
      underdiagnosis. Early identification and effective treatment of pediatric
      catatonia is critical given the significant morbidity and mortality associated
      with the condition. Given the widespread shortage of child and adolescent
      psychiatrists, at times consultation-liaison (C-L) psychiatrists without child
      training may be the frontline specialty providers asked to guide treatment of
      these pediatric patients. OBJECTIVE: To review the literature on pediatric
      catatonia using clinical cases to illustrate unique aspects of its presentation,
      evaluation, and management. METHODS: We describe the presentation and management
      of 6 adolescents with catatonia on an inpatient pediatric service at a general
      hospital and use these cases as a focal point for a review of the literature.
      CONCLUSION: Pediatric catatonia is a potentially lethal disease entity that can
      be effectively treated if accurately identified early in its course.
      Psychiatrists working in a C-L setting may encounter this syndrome and should be
      aware of its presentation, evaluation, and management.

PMID- 30104021
TI  - Serotonin Toxicity and Urinary Analgesics: A Case Report and Systematic
      Literature Review of Methylene Blue-Induced Serotonin Syndrome.
AB  - INTRODUCTION: Serotonin syndrome (SS) is a potentially serious side effect of
      serotonergic drugs. Cases of SS have been reported from the administration of
      methylene blue (MB), an agent with monoamine oxidase inhibiting properties. To
      date, the reported cases of MB-induced SS have all been with MB given
      parenterally. We report a case induced by the initiation of an MB-containing oral
      agent. METHODS: A case of SS felt to be induced by the initiation of an MB
      containing orally administered urinary analgesic, started in a patient
      concurrently treated with multiple serotonergic psychiatric drugs, is presented.
      A systematic literature review of MB-induced SS follows. The review consisted of
      searches in MEDLINE databases using the key terms "methylene blue" and "serotonin
      syndrome". The authors read all abstracts, articles related to MB and serotonin
      toxicity were then read in full; non-associated articles were discarded. Results
      are summarized. RESULTS: 23 manuscripts were identified, resulting in 50 unique
      cases of MB-induced SS. The majority of cases were related to peri-operative use
      of MB in parathyroidectomies or for the treatment of vasoplegic shock. All cases
      were associated with MB given parenterally. Concurrent treatment with
      serotonergic antidepressants was described in all 50 cases. Symptoms of SS ranged
      from mild to severe. One fatality was reported. CONCLUSIONS: Methylene blue can
      induce serotonin syndrome, felt to be secondary to MAOi properties. Although
      previous reports have exclusively been associated with MB given via parental
      administration, our case suggests that SS can be induced by oral administration
      of MB containing agents.

PMID- 30104022
TI  - Synthetic Cannabinoid-Associated Coagulopathy: Case Report.

PMID- 30104023
TI  - Access to Orthopedic Care post Medicaid Expansion Through the Affordable Care
      Act.
AB  - BACKGROUND: As of January 2017, 32 states have decided to expand Medicaid through
      the Patient Protection and Affordable Care Act. The uninsured rate in the United
      States has decreased, but does the increased coverage translate to increased
      access to outpatient orthopedic care? Through a simulated patient telephone
      survey, this study aims to evaluate access to orthopedic surgeons for Medicaid
      patients in Louisiana. METHODS: A comprehensive list of potentially eligible
      orthopedic surgeons in the state of Louisiana was obtained from an online public
      database managed by the Louisiana Medicaid website (lamedicaid.com). This list
      represented all orthopedic surgeons that received a Medicaid payment within the
      six months prior to February 1st, 2017 (August 1st, 2016-January 31st, 2017).
      Using an internet search, we found that 309 orthopedic surgeons listed met the
      inclusion criteria and were practicing in 93 different clinical practices.
      Because several orthopedists practiced in the same group practice, and some
      practiced in multiple practices, we sampled unique clinical practices as opposed
      to individual providers. One telephone call was made to each practice in an
      attempt to secure an appointment for a simulated Medicaid patient. The average
      number of orthopedic surgeons per practice was 3.4, with the majority of
      practices (60%) being private practices with only one surgeon. RESULTS: Of the 93
      practices in the study, only 17 (18.3%) offered an appointment. The 17 practices
      represented 41 orthopedic surgeons (13.3%) that were willing to accept new
      Medicaid patients. That number decreased to 22 (7.1%) if you remove the
      orthopedic surgeons practicing at safety-net facilities. CONCLUSION: The results
      suggest that although Medicaid expansion has decreased the uninsured rate, access
      to outpatient orthopedic care for Medicaid patients in Louisiana is still
      significantly limited.

PMID- 30104024
TI  - Primary Care Nurse Practitioner Wage Differences by Employment Setting.
AB  - BACKGROUND: Previous studies reported that primary care nurse practitioners
      working in primary care settings may earn less than those working in specialty
      care settings. However, few studies have examined why such wage difference
      exists. PURPOSE: This study used human capital theory to determine the degree to
      which the wage differences between dingsPCNPs working in primary care versus
      specialty care settings is driven by the differences in PCNPs' characteristics.
      Feasible generalized least squares regression was used to examine the wage
      differences for PCNPs working in primary care and specialty care settings.
      METHODS: A cross-sectional, secondary data analysis was conducted using the
      restricted file of 2012 National Sample Survey of Nurse Practitioners. FINDINGS:
      Oaxaca-Blinder decomposition technique was used to explore the factors
      contributing to wage differences.The results suggested that hourly wages of PCNPs
      working in primary care settings were, on average, 7.1% lower than PCNPs working
      in specialty care settings, holding PCNPs' socio-demographic, human capital, and
      employment characteristics constant. Approximately 4% of this wage difference was
      explained by PCNPs' characteristics; but 96% of these differences were due to
      unexplained factors. DISCUSSION: A large, unexplained wage difference exists
      between PCNPs working in primary care and specialty care settings.

PMID- 30104025
TI  - The multi-dimensional role of intestinal HIFs in liver pathobiology.

PMID- 30104027
TI  - A changing landscape of liver transplantation: King HCV is dethroned, ALD and
      NAFLD take over!

PMID- 30104028
TI  - Are preoperative serum CA15-3 levels different in breast cancer subgroups?
AB  - PURPOSE: Breast cancer classifies to 4 major subgroups according to
      immunohistochemistry staining features as Luminal A, Luminal B, human epidermal
      growth factor receptor 2 overexpression, and Triple Negative. Cancer Antigen15-3
      (CA15-3) is used as a tumor marker in breast cancer while its value in early
      stage and in breast cancer subgroups is still controversial. In this study, we
      aimed to investigate that whether it is or not differences of the serum
      preoperative CA15-3 levels in early breast cancer subgroups. METHODS: We
      retrospectively investigated medical records of 751 breast cancer patients who
      admitted to Afyon Kocatepe University Department of Medical Oncology between
      January 2010 and December 2016. Total 361 patients were included in this study.
      The cut off value of Ki-67 was used as 20 to distinguish between Luminal A from
      Luminal B subgroups. Cutoff values of CA15-3 were evaluated as 25U/mL. RESULTS:
      CA15-3 levels were not significantly different according to clinical features.
      Molecular subgroups were similar in CA15-3 levels (P = 0.666). Elevated levels of
      CA15-3 >= 25 U/mL were found 34 patients (20.5%) in Luminal A, 15 patients
      (28.3%) in Luminal B1, 15 patients (20.3%) in Luminal B2, 7 patients (25%) in
      human epidermal growth factor receptor 2 overexpressed and 9 patients (22.5%) in
      triple negative groups. CONCLUSION: There was no relationship preoperative CA15-3
      levels and breast cancer subgroups.

PMID- 30104026
TI  - Corrigendum to "Prognostic factors and predictors of sorafenib benefit in
      patients with hepatocellular carcinoma: Analysis of two phase III studies" [J
      hepatol 67 (2017) 999-1008].

PMID- 30104029
TI  - Retrospective evaluation of patients diagnosed solid pseudopapillary neoplasms of
      the pancreas.
AB  - PURPOSE: Solid pseudopapillary neoplasm (SPN) is a rare, low-grade neoplasm with
      excellent prognosis. In this study, we evaluated clinicopathological
      characteristics of patients diagnosed with SPN retrospectively. METHODS: This is
      a retrospective study intended to characterize patients with the diagnosis of SPN
      between 2005 and 2015. Clinicopathological features, recurrence rate, and overall
      survival of 28 patients were recorded. Malignant SPN criteria were defined as the
      presence of distant metastasis (developed at diagnosis or during follow up) or
      lymph node involvement. RESULTS: The mean age at diagnosis was 42 (range: 17-41).
      Among patients, 82% (n = 23) were female and 17.9% (n = 5) were male. The mean
      size of tumor was 5.81 cm (range: 2-15). The mean follow up period was 55.6
      months, 1-year survival was 96.5% and 5-year survival rate was 88%. A total of 25
      patients were alive at the end of follow-up period and 3 of the patients became
      exitus due to disease. Two patients had a metastatic presentation in livers at
      the diagnosis and metastasis developed in 3 patients during follow-up (liver of 1
      patient, peritoneum in 1 patient and liver and peritoneum in 1 patient). The
      reason of admission was headache in 68% patients. The type of operation was
      frequently subtotal pancreatectomy (n = 11, 39.3%) and distal pancreatectomy (n =
      10, 35.7%). Tumors were located frequently in body and tail regions (n = 18,
      64.3%) and the number of patients with malignant criteria was 6 (21.4%). Although
      the mean age of malignant patients was significantly higher than benign patients
      (P = 0.046), there was no significant difference between 2 groups in terms of
      gender, tumor size, capsule invasion, perineural invasion, vascular invasion, and
      margin status. CONCLUSION: SPN is a rarely seen tumor with low malignity
      potential. Surgical resection provides long-term survival rate even in local
      invasion or metastasis conditions.

PMID- 30104030
TI  - Current uses of check inhibitors in the fight against advanced and/or metastatic
      lung cancer: will immunotherapy overcome chemotherapy?
AB  - Lung cancer is the most common cause of cancer death worldwide. Treatment for
      lung cancer has become increasingly more complex over the last several years.
      Immune checkpoint inhibitors have dramatically changed the treatment landscape of
      advanced nonsmall cell lung cancer (NSCLC). There are currently 3 approved
      checkpoint inhibitors for patients with NSCLC who progressed after platinum
      doublet chemotherapy (Pembrolizumab and /or Nivolumab and /or Atezolizumab).
      Avelumab and durvalumab are currently under investigation in phase 3 trials.
      Pembrolizumab has now been approved for first-line use in NSCLC, after a trial
      showed improved survival compared with chemotherapy in patients who were positive
      for programmed cell death ligand 1. Giving our patients the best, personalized
      approach to their individual cancer can improve their quality of life and
      survival and help us use our limited resources most efficiently. In the present
      review, we provide a new patient-oriented algorithm to guide clinicians'
      decisions on the best choice of therapy for advanced NSCLC.

PMID- 30104031
TI  - Management of cardiac implantable devices in patients undergoing radiotherapy.
AB  - The delivery of radiotherapy to patients with a cardiac implantable electronic
      device (CIED) is not an infrequent event. Consideration of the potential issues
      for patients is an important part of their care. An overview of CIEDs is
      provided, including the potential problems encountered and the steps that can be
      taken to mitigate this risk.

PMID- 30104032
TI  - Transcatheter aortic valve implantation in patients younger than 75 years:
      Guidelines-based patients selection and clinical outcome.
AB  - BACKGROUND: Patients treated by transcatheter aortic valve implantation (TAVI) in
      all major recent trials are still mostly octogenarians. Aim of this study is to
      analyze the risk profile and outcome of TAVI patients <75 years. METHODS AND
      RESULTS: We retrospectively analyzed 172 patients <75 years with symptomatic
      severe native AS or degeneration of surgical aortic bioprosthesis treated with
      TAVI. The level of surgical risk was reassessed according to multiparametric ACC
      classification (prohibitive in 68 patients, high in 34, intermediate in 70). Mean
      age was 69.02 +/- 6.18 years, mean STS score 5.56 +/- 5.21. The majority of them
      presented one or more clinical or anatomical characteristics favoring TAVI
      according to ECS guidelines, despite the young age. Vascular access was
      transfemoral in 76%. According to the VARC-2 definitions, device success was high
      (90%) in all groups. The early safety was 89%, clinical recovery was slower in
      prohibitive risk patients. Bleeding events were more frequent in prohibitive and
      high surgical risk classes. Clinical efficacy at 1 year was overall 83%, and
      significantly better in intermediate risk patients (p = 0.004). The functional
      status remained stable over time as well as prostheses performance. CONCLUSION:
      About 40% of patients <75 years were treated by TAVI due to the presence of a
      prohibitive risk, mainly related to technical impediments. The remaining was
      referred to TAVI due to an estimated high or intermediate surgical risk driven by
      STS score, frailty and/or major organ system compromise. Early and mid-term
      clinical and hemodynamic outcomes were good, in particular in intermediate risk
      patients.

PMID- 30104034
TI  - Heart rate variability as a marker of healthy ageing.
AB  - BACKGROUND: With population ageing a significant concern, modifiable factors
      contributing to healthy ageing must be identified. Autonomic responding reflected
      by heart rate variability (HRV) has well-established links to general health and
      wellbeing in younger populations; but has yet to be explored in older
      individuals. METHODS: Forty-five healthy participants (49-82 years old) completed
      questionnaires about sleep and physical and psychological health. Autonomic
      activity was measured during rest and whilst completing a computerised battery of
      cognitive tasks. Participants then wore an ambulatory heart rate monitor
      overnight, and recorded their sleep and physical activity for one week. HRV
      parameters reflecting cardiac vagal tone were derived from electrocardiograph
      recordings. RESULTS: Age and resting HRV were not related; however a positive
      association was identified between higher HRV in the 2 h prior to sleep and older
      age. Higher resting HRV, older age, and better sleep quality significantly
      predicted psychological wellbeing; and fewer somatic and physical health symptoms
      and older age predicted better average sleep quality ratings. Older age and
      poorer general health were significant predictors of cognitive performance
      deficits. CONCLUSION: These findings suggest that an age-related decline in HRV
      is not inevitable. Longitudinal designs exploring within-individual changes in
      cardiac vagal tone are required to better understand the factors contributing to
      healthy ageing.

PMID- 30104035
TI  - Closed Emergency Department Reduction of a Superior Patellar Dislocation After
      Blunt Trauma.

PMID- 30104033
TI  - Delayed pacemaker requirement after transcatheter aortic valve implantation with
      a new-generation balloon expandable valve: Should we monitor longer?
AB  - OBJECTIVES: To analyze the timing of appearance of conduction abnormalities (CAs)
      after transcatheter aortic valve implantation (TAVI), to identify predictors of
      delayed CAs requiring pacemaker (PM) implantation and to provide guidance
      regarding the duration of telemetry monitoring. BACKGROUND: How long patients
      remain at risk of development of CAs requiring PM implantation after TAVI and for
      how long they should be monitored remains unclear but is crucial when considering
      early discharge. METHODS: Development of CAs was studied in 701 consecutive
      patients treated with Edwards Sapien 3 valves and monitored with telemetry for 7
      days in a single center. After excluding valve-in-valve procedures and patients
      with previous PM, 606 patients remained for analysis. Predictors of CAs requiring
      PM and the time of onset of CAs were analyzed. RESULTS: Of 606 patients 76
      (12.5%) required a PM after TAVI. CAs requiring PM implantation occurred after 48
      h in 22.4% (17 patients) and in 10.5% (8 patients) even after 5 days. Of the
      patients who developed high grade CAs requiring PM after 48 h, 47.1% had no CAs
      prior to TAVI, and 23.5% had neither pre-existing CAs nor new-developed CAs
      within the first 48 h after TAVI. CONCLUSION: After TAVI using a new-generation
      balloon-expandable valve, delayed development of CAs requiring PM implantation is
      not uncommon, even after 5 days. More importantly, 23.5% of patients eventually
      requiring a delayed PM implantation had still no CAs at 48 h after TAVI in this
      study. These results question the safety of early discharge and support ECG
      monitoring for a longer time period. The most optimal way to monitor these
      patients is yet to be determined.

PMID- 30104037
TI  - Design of high performance QRS complex detector for wearable healthcare devices
      using biorthogonal spline wavelet transform.
AB  - A high performance QRS complex detector applicable for wearable healthcare
      devices is proposed in the present work. Since, higher SNR results in better
      detection accuracy and lesser number of coefficients reduces the hardware
      resources as well as power dissipation during on chip implementation.
      Biorthogonal spline wavelet transform is chosen for the proposed detector as it
      has high signal to noise ratio (SNR) and uses only four coefficients for
      decomposition. In the proposed approach, a Biorthogonal wavelet filter bank with
      fourth level decomposition is first used to separate the different frequency
      components and then a fourth level wavelet filter bank is used to get the
      denoised electrocardiogram (ECG) signals. Wavelet filter bank outputs are
      multiplied and soft threshold method is applied to get the QRS complex peaks by
      the QRS complex peak detector block. Add and shift multiplier used in the earlier
      designs has been replaced by a Booth multiplier in our approach to achieve the
      higher performance. Booth multiplier and QRS complex peak detector blocks have
      been designed for low hardware complexity, high performance and accurate
      detection of the QRS complex peaks. Time interval between the consecutive QRS
      peaks is calculated using the R-R peak time calculator block and the heart rate
      (HR) by the HR calculator block. Heart Rate Variability (HRV) and arrhythmia are
      detected based on these heart rate calculations. Proposed design has been tested
      for its robustness on multiple datasets (namely, MIT-BIH arrhythmia, MIT-BIH
      noise stress test, and MIT-BIH atrial fibrillation databases). Sensitivity of
      99.31%, positive predictivity of 99.19% and the Detection Error Rate (DER) of
      1.49% shown by the proposed design makes it preferable for QRS complex detectors
      used in wearable healthcare devices.

PMID- 30104036
TI  - Command filter based adaptive fuzzy bipartite output consensus tracking of
      nonlinear coopetition multi-agent systems with input saturation.
AB  - This paper is concerned with the adaptive bipartite output consensus tracking
      problem of high-order nonlinear coopetition multi-agent systems with input
      saturation under a signed directed graph. A distributed fuzzy-based command
      filtered backstepping scheme is proposed, where the unknown nonlinear dynamics
      are approximated by the fuzzy logic system (FLS). The errors compensation
      mechanism is constructed to eliminate the errors caused by filters. Under the
      proposed control scheme, we only need to design one adaptive law for each agent,
      and it is proved that the bipartite output tracking errors converge into the
      desired neighborhood and all the closed-loop signals are bounded although the
      input saturation exists. Two numerical examples are included to verify the
      effectiveness of given scheme.

PMID- 30104038
TI  - Patient-Reported Visual Disability in Fuchs' Endothelial Corneal Dystrophy
      Measured by the Visual Function and Corneal Health Status Instrument.
AB  - PURPOSE: Measuring patient-reported visual disability in Fuchs' endothelial
      corneal dystrophy (FECD) may be helpful in determining when to intervene and for
      understanding the outcomes of intervention. In this study, we aimed to validate a
      new patient-reported visual disability questionnaire, the Visual Function and
      Corneal Health Status (V-FUCHS) instrument, in FECD before and after endothelial
      keratoplasty (EK). DESIGN: Cross-sectional study with instrument readministration
      at 6 weeks. PARTICIPANTS: Patients with a range of severity of FECD, including
      after EK, and patients with healthy corneas. METHODS: The V-FUCHS instrument was
      developed based on patient interviews, expert consultations, and pretesting.
      Psychometric methods of classic test theory were applied to estimate reliability
      and validity, including testing V-FUCHS against Catquest-9SF, a cataract-specific
      visual disability questionnaire. Ordered polytomous Rasch-based partial credit
      models and item response theory diagnostics were used to define the response
      patterns. MAIN OUTCOME MEASURES: Reliability (primary) and validity (secondary).
      RESULTS: The final instrument was completed by 65% of patients with a range of
      severity of FECD (n = 41), after undergoing EK for FECD (n = 70), and with
      healthy corneas (n = 28). Participants were phakic or pseudophakic. Exploratory
      factor analysis among FECD and patients who underwent EK showed 2 independent
      factors of visual disability: 7 items related to visual acuity and 8 items
      related to glare or diurnal variation. Retest reliability was substantial
      (intraclass correlation coefficient, >=0.8, both factors). Among all patients,
      the visual acuity factor was correlated with Catquest-9SF scores (r = 0.65; P <
      0.001; n = 96). The glare or diurnal variation factor increased with FECD
      severity (P < 0.001, n = 69) and was higher in FECD than healthy participants (P
      < 0.001). Diagnostics revealed that both factors were well calibrated and met
      Rasch model expectations. CONCLUSIONS: The V-FUCHS instrument is valid and
      reliable for assessing visual disability in FECD. The instrument allows for
      standardized, comprehensive, and rapid assessment of disease-specific visual
      disability and may be useful in clinical practice and research as a patient
      reported outcome measure.

PMID- 30104039
TI  - The Importance and Psychology of Facial Expression.
AB  - Facial expression is of critical importance in interpersonal interactions. Thus,
      patients with impaired facial expression due to facial paralysis experience
      impaired social interactions. Numerous studies have shown that patients with
      facial paralysis and impaired facial expression suffer social consequences as
      demonstrated by being rated negatively with regards to attractiveness, affect
      display, and other traits. This has been demonstrated subjectively and
      objectively. Fortunately, reconstructive surgeries that restore the ability to
      express emotion can restore normalcy in these patients.

PMID- 30104040
TI  - Free Gracilis Transfer and Static Facial Suspension for Midfacial Reanimation in
      Long-Standing Flaccid Facial Palsy.
AB  - This article presents an approach to reanimation of the midface in long-standing
      flaccid facial palsy by means of functional free gracilis transfer and static
      facial suspension.

PMID- 30104042
TI  - 72-Year-Old Woman With Fatigue, Confusion, and Severe Acute Renal Failure.

PMID- 30104041
TI  - Development and Validation of Prediction Scores for Early Mortality at Transition
      to Dialysis.
AB  - OBJECTIVE: To develop and validate a risk prediction model that would help
      individualize treatment and improve the shared decision-making process between
      clinicians and patients. PATIENTS AND METHODS: We developed a risk prediction
      tool for mortality during the first year of dialysis based on pre-end-stage renal
      disease characteristics in a cohort of 35,878 US veterans with incident end-stage
      renal disease who transitioned to dialysis treatment between October 1, 2007, and
      March 31, 2014 and then externally validated this tool among 4284 patients in the
      Kaiser Permanente Southern California (KPSC) health care system who transitioned
      to dialysis treatment between January 1, 2007, and September 30, 2015. RESULTS:
      To ensure model goodness of fit, 2 separate models were selected for patients
      whose last estimated glomerular filtration rate (eGFR) before dialysis initiation
      was less than 15 mL/min per 1.73 m2 or 15 mL/min per 1.73 m2 or higher. Model
      discrimination in the internal validation cohort of veterans resulted in C
      statistics of 0.71 (95% CI, 0.70-0.72) and 0.66 (95% CI, 0.65-0.67) among
      patients with eGFR lower than 15 mL/min per 1.73 m2 and 15 mL/min per 1.73 m2 or
      higher, respectively. In the KPSC external validation cohort, the developed risk
      score exhibited C statistics of 0.77 (95% CI, 0.74-0.79) in men and 0.74 (95% CI,
      0.71-0.76) in women with eGFR lower than 15 mL/min per 1.73 m2 and 0.71 (95% CI,
      0.67-0.74) in men and 0.67 (95% CI, 0.62-0.72) in women with eGFR of 15 mL/min
      per 1.73 m2 or higher. CONCLUSION: A new risk prediction tool for mortality
      during the first year after transition to dialysis (available at
      www.DialysisScore.com) was developed in the large national Veterans Affairs
      cohort and validated with good performance in the racially, ethnically, and
      gender diverse KPSC cohort. This risk prediction tool will help identify high
      risk populations and guide management strategies at the transition to dialysis.

PMID- 30104043
TI  - Onco-Epilepsy: More Than Tumor and Seizures.

PMID- 30104044
TI  - Risk of Severe Cardiovascular Events From Add-On Tiotropium in Chronic
      Obstructive Pulmonary Disease.
AB  - OBJECTIVE: To examine the risk of cardiovascular disease (CVD) from tiotropium
      added to inhaled long-acting beta2 agonists (LABAs) and inhaled corticosteroids
      (ICSs) in a nationwide population with chronic obstructive pulmonary disease
      (COPD). PATIENTS AND METHODS: This nested case-control study included 65,966
      patients with COPD treated with LABAs and ICSs identified from the Taiwan
      nationwide health care claims database from January 1, 2007, through June 30,
      2011. Cases were all patients with a first primary diagnosis of ischemic heart
      disease, heart failure, stroke, or arrhythmia from inpatient or emergency care
      settings during follow-up, and each was matched with 4 disease risk score-matched
      controls from risk sets. The use of tiotropium in the year before the index/event
      date was measured, stratified by duration since therapy initiation, concomitant
      COPD medications, and dosage form. Conditional logistic regression models were
      used to estimate odds ratios of the CVD risk from add-on tiotropium therapy.
      RESULTS: From the study cohort, with a mean age of 70.3 years (interquartile
      range, 61.8-79.4 years), 3188 CVD cases (incidence rate, 6.2 [95% CI, 6.0-6.4]
      cases per 100 person-years) and 12,349 matched controls were identified. The new
      use of tiotropium was associated with a 1.88-fold (95% CI, 1.44-2.46) increased
      CVD risk within 30 days of therapy initiation, and the association was sustained
      up to 60 days after treatment initiation (adjusted odds ratio, 1.71; 95% CI, 1.08
      2.70). The risk persisted across all tiotropium regimens, with a case-crossover
      analysis, and in comparison with new add-on theophylline therapy. CONCLUSION:
      Tiotropium newly added to LABA/ICS combination therapy was associated with an
      increased cardiovascular risk in patients with COPD.

PMID- 30104045
TI  - 59-Year-Old Man With Fatigue, Weight Loss, and Hepatomegaly.

PMID- 30104046
TI  - New opportunities for malaria vector control.

PMID- 30104047
TI  - Efficacy of Olyset Duo, a bednet containing pyriproxyfen and permethrin, versus a
      permethrin-only net against clinical malaria in an area with highly pyrethroid
      resistant vectors in rural Burkina Faso: a cluster-randomised controlled trial.
AB  - BACKGROUND: Substantial reductions in malaria incidence in sub-Saharan Africa
      have been achieved with massive deployment of long-lasting insecticidal nets
      (LLINs), but pyrethroid resistance threatens control. Burkina Faso is an area
      with intense malaria transmission and highly pyrethroid-resistant vectors. We
      assessed the effectiveness of bednets containing permethrin, a pyrethroid, and
      pyriproxyfen, an insect growth regulator, versus permethrin-only (standard) LLINs
      against clinical malaria in children younger than 5 years in Banfora, Burkina
      Faso. METHODS: In this two-group, step-wedge, cluster-randomised, controlled,
      superiority trial, standard LLINs were incrementally replaced with LLINs treated
      with permethrin plus pyriproxyfen (PPF) in 40 rural clusters in Burkina Faso. In
      each cluster, 50 children (aged 6 months to 5 years) were followed up by passive
      case detection for clinical malaria. Cross-sectional surveys were done at the
      start and the end of the transmission seasons in 2014 and 2015. We did monthly
      collections from indoor light traps to estimate vector densities. Primary
      endpoints were the incidence of clinical malaria, measured by passive case
      detection, and the entomological inoculation rate. Analyses were adjusted for
      clustering and for month and health centre. This trial is registered as
      ISRCTN21853394. FINDINGS: 1980 children were enrolled in the cohort in 2014 and
      2157 in 2015. At the end of the study, more than 99% of children slept under a
      bednet. The incidence of clinical malaria was 2.0 episodes per child-year in the
      standard LLIN group and 1.5 episodes per child-year in the PPF-treated LLIN group
      (incidence rate ratio 0.88 [95% CI 0.77-0.99; p=0.04]). The entomological
      inoculation rate was 85 (95% CI 63-108) infective bites per transmission season
      in the standard LLIN group versus 42 (32-52) infective bites per transmission
      season in the PPF-treated LLIN group (rate ratio 0.49, 95% CI 0.32-0.66;
      p<0.0001). INTERPRETATION: PPF-treated LLINs provide greater protection against
      clinical malaria than do standard LLINs and could be used as an alternative to
      standard LLINs in areas with intense transmission of Plasmodium falciparum
      malaria and highly pyrethroid-resistant vectors. FUNDING: EU Seventh Framework
      Programme.

PMID- 30104049
TI  - [Coinfection with hydatid cyst and pulmonary tuberculosis].
AB  - Morocco is an endemic area for both hydatid cyst and tuberculosis (TB). The co
      occurrence of these two diseases in lung is unusual, especially when localized in
      the same area. We describe the case of a patient with pulmonary hydatid cyst
      associated with tuberculosis infection where the diagnosis was unknown prior to
      surgery because TB tests were negative. The surgical resection was very difficult
      because of inflammation in the surrounding tissue and its fragility. However, the
      postoperative course was uneventful. The goal of this case report is to keep in
      mind that such co-infection is possible especially in endemic countries.

PMID- 30104050
TI  - Contributors to the length-of-stay trajectory in burn-injured patients.
AB  - OBJECTIVES: Burn patients have a highly variable length-of-stay (LOS) due to the
      complexity of the injury itself. The LOS for burn patients is estimated as one
      day per percent total body surface area (TBSA) burn. To focus care expectation
      and prognosis we aimed to identify key factors that contribute to prolonged LOS.
      METHODS: This was a retrospective cohort-study (2006-2016) in an adult burn
      centre that included patients with >=10% TBSA burn. Patients were stratified into
      expected-LOS (<2 days LOS/%TBSA) and longer-than-expected-LOS (>=2 days
      LOS/%TBSA). We assessed demographics, comorbidities, and in-hospital
      complications. Logistic regression and propensity matching was utilized. RESULTS:
      Of the 583 total patients, 477 had an expected-LOS whereas 106 a longer-than
      expected-LOS. Non-modifiable factors such as age, 3rd degree TBSA%, inhalation
      injuries and comorbidities were greater in the exceeded LOS patients. Subsequent
      matched analysis revealed factors like number of procedures performed, days
      ventilated and in-hospital complications (bacteremia, pneumonia, sepsis, graft
      loss, and respiratory failure) were significantly increased in the longer-than
      expected-LOS group. CONCLUSIONS: Progress has been made to update the
      conventional one day/%TBSA to better aid health care providers in giving
      appropriate outcomes for patients and their families and to supply intensive care
      units with valuable data to assess quality of care and to improve patient
      prognosis.

PMID- 30104048
TI  - Prevention of Ebola virus disease through vaccination: where we are in 2018.

PMID- 30104051
TI  - Adrenocortical carcinoma (ACC): When and why should we consider germline testing?
AB  - Adrenocortical carcinoma (ACC), particularly when occurring during childhood, has
      been a traditional component of the tumor spectrum of Li-Fraumeni syndrome.
      Recent research has defined a significant risk increase of ACC with other
      familial cancer syndromes, such as Lynch syndrome and multiple endocrine
      neoplasia. ACC patients can serve as index patients for a new family diagnosis of
      a hereditary syndrome, allowing for further family cascade genetic testing,
      impacting the care and surveillance for patients and at risk family members.
      Individuals carrying pathogenic genetic variants can embark on a regular
      preventive screening and surveillance protocol likely reducing morbidity and
      mortality. Although several of these hereditary predisposition syndromes lead to
      a very high relative risk increase for ACC, the absolute risk most often does not
      reach a level to recommend general screening for ACC in carriers of pathogenic
      mutations. The larger value lies in the ability to screen for other commonly
      associated tumors in pathogenic variant carriers, such as colon cancer with Lynch
      syndrome. Here, we review the risk for ACC associated with hereditary syndromes
      and suggest an approach for genetic evaluation for ACC patients.

PMID- 30104052
TI  - A computational framework for adjusting flow during peripheral extracorporeal
      membrane oxygenation to reduce differential hypoxia.
AB  - Peripheral veno-arterial extra corporeal membrane oxygenation (VA-ECMO) is an
      established technique for short-to-medium support of patients with severe cardiac
      failure. However, in patients with concomitant respiratory failure, the residual
      native circulation will provide deoxygenated blood to the upper body, and may
      cause differential hypoxemia of the heart and brain. In this paper, we present a
      general computational framework for the identification of differential hypoxemia
      risk in VA-ECMO patients. A range of different VA-ECMO patient scenarios for a
      patient-specific geometry and vascular resistance were simulated using transient
      computational fluid dynamics simulations, representing a clinically relevant
      range of values of stroke volume and ECMO flow. For this patient, regardless of
      ECMO flow rate, left ventricular stroke volumes greater than 28 mL resulted in
      all aortic arch branch vessels being perfused by poorly-oxygenated systemic blood
      sourced from the lungs. The brachiocephalic artery perfusion was almost entirely
      derived from blood from the left ventricle in all scenarios except for those with
      stroke volumes less than 5 mL. Our model therefore predicted a strong risk of
      differential hypoxemia in nearly all situations with some residual cardiac
      function for this combination of patient geometry and vascular resistance. This
      simulation highlights the potential value of modelling for optimising ECMO design
      and procedures, and for the practical utility for personalised approaches in the
      clinical use of ECMO.

PMID- 30104053
TI  - Predicting the influence of hip and lumbar flexibility on lifting motions using
      optimal control.
AB  - Computational models of the human body coupled with optimization can be used to
      predict the influence of variables that cannot be experimentally manipulated.
      Here, we present a study that predicts the motion of the human body while lifting
      a box, as a function of flexibility of the hip and lumbar joints in the sagittal
      plane. We modeled the human body in the sagittal plane with joints actuated by
      pairs of agonist-antagonist muscle torque generators, and a passive hamstring
      muscle. The characteristics of a stiff, average and flexible person were
      represented by co-varying the lumbar range-of-motion, lumbar passive extensor
      torque and the hamstring passive muscle-force. We used optimal control to solve
      for motions that simulated lifting a 10 kg box from a 0.3 m height. The solution
      minimized the total sum of the normalized squared active and passive muscle
      torques and the normalized passive hamstring muscle forces, over the duration of
      the motion. The predicted motion of the average lifter agreed well with
      experimental data in the literature. The change in model flexibility affected the
      predicted joint angles, with the stiffer models flexing more at the hip and knee,
      and less at the lumbar joint, to complete the lift. Stiffer models produced
      similar passive lumbar torque and higher hamstring muscle force components than
      the more flexible models. The variation between the motion characteristics of the
      models suggest that flexibility may play an important role in determining lifting
      technique.

PMID- 30104054
TI  - Joint moments' contributions to vertically accelerate the center of mass during
      stair ambulation in the elderly: An induced acceleration approach.
AB  - Falls are a serious problem faced by the elderly. Older adults report mostly to
      fall while performing locomotor activities, especially the ones requiring stair
      negotiation. During these tasks, older adults, when compared with young adults,
      seem to redistribute their lower limb joint moments. This may indicate that older
      adults use a different strategy to accelerate the body upward during these tasks.
      The purposes of this study were to quantify the contributions of each lower limb
      joint moment to vertically accelerate the center of mass during stair ascent and
      descent, in a sample of community-dwelling older adults, and to verify if those
      contributions were correlated with age and functional fitness level. A joint
      moment induced acceleration analysis was performed in 29 older adults while
      ascending and descending stairs at their preferred speed. Agreeing with previous
      studies, during both tasks, the ankle plantarflexor and the knee extensor joint
      moments were the main contributors to support the body. Although having a smaller
      contribution to vertically accelerate the body, during stair descent, the hip
      joint moment contribution was related with the balance score. Further, older
      adults, when compared with the results reported previously for young adults, seem
      to use more their knee extensor moment than the ankle plantarflexor moment to
      support the body when the COM downward velocity is increasing. By contributing
      for a better understanding of stair negotiation in community dwelling older
      adults, this study may help to support the design of interventions aiming at fall
      prevention and/or mobility enhancement within this population.

PMID- 30104056
TI  - Translational Research - Interventions for Promoting Health in Children.

PMID- 30104057
TI  - Translation, Cross-Cultural Adaptation, and Psychometric Testing of Perception of
      Family-Centered Care Measurement Questionnaires in the Hospitalized Children in
      Iran.
AB  - PURPOSE: This study aimed to offer a translation, cross-cultural adaptation, and
      psychometric testing of the Perception of Family-Centered Care-Staff (PFCC-S) and
      Perception of Family-Centered Care-Parents (PFCC-P) questionnaires for use in
      pediatric nursing in Iran. DESIGN AND METHODS: The study was comprised of six
      steps. The first five steps included the preparation, forward translation,
      reconciliation, back translation, and back translation review of the translated
      questionnaires. In the sixth step, the content validity ratio, content validity
      index, confirmatory factor analysis, and reliability were estimated. Through the
      convenience sampling method, 456 nurses and mothers were included in the study
      for confirmatory factor analysis, while 40 nurses and mothers were selected to
      evaluate the reliability of the two questionnaires. RESULTS: Harmonized versions
      of the Persian PFCC-S and PFCC-P questionnaires were developed (steps 1-5). The
      content validity ratio of all items of the questionnaires was >0.62. The content
      validity index for the PFCC-S and PFCC-P questionnaires was 0.81 and 0.83,
      respectively. One item was added to each questionnaire, which contained 21 items.
      The confirmatory factor analysis verified the three subscales of respect,
      collaboration, and support in the two questionnaires. The intraclass correlation
      and Cronbach's alpha coefficients for the PFCC-S questionnaire were 0.89 and
      0.87, respectively, and 0.79 and 0.81, respectively, for the PFCC-P
      questionnaire. CONCLUSIONS: This study developed questionnaires that were
      compatible with the Iranian culture to measure the perception of family-centered
      care. PRACTICE IMPLICATIONS: Nurses can use these questionnaires to measure and
      compare the perceptions of family-centered care by staff and parents.

PMID- 30104055
TI  - Joint contact stresses calculated for acetabular dysplasia patients using
      discrete element analysis are significantly influenced by the applied gait
      pattern.
AB  - Gait modifications in acetabular dysplasia patients may influence cartilage
      contact stress patterns within the hip joint, with serious implications for
      clinical outcomes and the risk of developing osteoarthritis. The objective of
      this study was to understand how the gait pattern used to load computational
      models of dysplastic hips influences computed joint mechanics. Three-dimensional
      pre- and post-operative hip models of thirty patients previously treated for hip
      dysplasia with periacetabular osteotomy (PAO) were developed for performing
      discrete element analysis (DEA). Using DEA, contact stress patterns were
      calculated for each pre- and post-operative hip model when loaded with an
      instrumented total hip, a dysplastic, a matched control, and a normal gait
      pattern. DEA models loaded with the dysplastic and matched control gait patterns
      had significantly higher (p = 0.012 and p < 0.001) average pre-operative maximum
      contact stress than models loaded with the normal gait. Models loaded with the
      dysplastic and matched control gait patterns had nearly significantly higher (p =
      0.051) and significantly higher (p = 0.008) average pre-operative contact stress,
      respectively, than models loaded with the instrumented hip gait. Following PAO,
      the average maximum contact stress for DEA models loaded with the dysplastic and
      matched control patterns decreased, which was significantly different (p < 0.001)
      from observed increases in maximum contact stress calculated when utilizing the
      instrumented hip and normal gait patterns. The correlation between change in DEA
      computed maximum contact stress and the change in radiographic measurements of
      lateral center-edge angle were greatest (R2 = 0.330) when utilizing the
      dysplastic gait pattern. These results indicate that utilizing a dysplastic gait
      pattern to load DEA models may be a crucial element to capturing contact stress
      patterns most representative of this patient population.

PMID- 30104058
TI  - Destructive stationary phase gradients for reversed-phase/hydrophilic interaction
      liquid chromatography.
AB  - The use of stationary phase gradients for liquid chromatography (LC) is a
      promising new strategy to allow for specific control over the selectivity of a
      separation by having a gradual change in the ligand density along the length of
      the column. Unfortunately, there have been very few, if any, methods to prepare
      continuous stationary phase gradients on traditional packed LC columns. In this
      work, destructive methodologies are used to create stationary phase gradients on
      commercial C18 columns by infusing trifluoroacetic acid (TFA) onto the column
      through controlled rate of infusion (CRI). The introduction of TFA via CRI while
      the column is heated at 80  degrees C promotes acid hydrolysis of the alkylsilane
      ligand in a gradient fashion. Characterization with scanning electron microscopy
      and Barrett-Joyner-Halenda pore size distributions of the stationary phase after
      fabrication of the destructive gradient establishes that the chromatographic
      support was not damaged during the procedure. The shape of the gradient was
      examined using thermogravimetric analysis (TGA) and attenuated total reflectance
      Fourier transform infrared (ATR-FTIR) spectroscopy. TGA and ATR-FTIR showed an
      increase in the percent carbon loss along the length of the column, indicating
      that there was an increase in the C18 ligand from the front to the end of the
      column. Two selectivity tests demonstrated a decrease in the hydrophobicity and
      increase in the silanol activity of the stationary phase gradient from the
      uniform C18 counterpart. Additionally, the fabrication of the destructive
      stationary phase gradient resulted in two different surface functionalities
      allowing hydrophobic and hydrophilic interactions with analyte species depending
      on the mobile phase composition. Plots of the log of retention factor versus
      percent acetonitrile illustrated that these stationary phase gradients have two
      separation mechanisms: reversed-phase (RP) and hydrophilic interaction. Coupling
      the stationary phase gradient with a mobile phase gradient shows differences in
      the peak widths and the resolution of phenolic compounds, indicating that the
      orientation of the stationary phase gradient has the potential to enhance the
      resolution of a separation. With this methodology, stationary phase gradients can
      be fabricated on previously used RP columns, allowing for these columns to be
      repurposed.

PMID- 30104059
TI  - Development of an online two-dimensional high-performance liquid chromatographic
      system in combination with tandem mass spectrometric detection for enantiomeric
      analysis of free amino acids in human physiological fluid.
AB  - An automated two-dimensional HPLC-MS/MS system was designed and developed for the
      highly selective determination of trace levels of d-amino acids. As the targets,
      frequently observed ones in mammalian physiological fluids, Ala, Asp, Glu, Leu,
      Pro and Ser, were selected because these d-amino acids are the potential
      biomarkers for the early and sensitive diagnoses of various diseases. The target
      analytes were derivatized with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F),
      then isolated by a reversed-phase column in the first dimension. The NBD-amino
      acid fractions were automatically collected into the multi-loop device, and
      introduced into the enantioselective column in the second dimension to separate
      the d- and l-forms followed by detection by an MS/MS. The obtained resolution
      values of the enantiomers were 1.87-5.17 and the calibration lines, precision and
      accuracy were practically sufficient. By using the present 2D HPLC-MS/MS system,
      trace levels of d-amino acids in complex biological matrices were determined
      without disturbance by the intrinsic interfering compounds, and successfully
      applied to the analysis of the human clinical samples (plasma and urine).

PMID- 30104060
TI  - A linear epitope coupled to DsRed provides an affinity ligand for the capture of
      monoclonal antibodies.
AB  - Monoclonal antibodies (mAbs) dominate the market for biopharmaceutical proteins
      because they provide active and passive immunotherapies for many different
      diseases. However, for most mAbs, two expensive manufacturing platforms are
      required. These are mammalian cell cultures for upstream production and Protein A
      chromatography for product capture during downstream processing. Here we describe
      a novel affinity ligand based on the fluorescent protein DsRed as a carrier for
      the linear epitope ELDKWA, which can capture the HIV-neutralizing antibody 2F5.
      We produced the DsRed-2F5-Epitope (DFE) in transgenic tobacco (Nicotiana tabacum)
      plants and purified it using a combination of heat treatment and immobilized
      metal-ion affinity chromatography, resulting in a yield of 24 mg kg-1 at 90%
      purity. Using a design-of-experiments approach, we coupled up to 15 mg DFE per mL
      Sepharose. The resulting affinity resin was able to capture 2F5 from the
      clarified extract of N. benthamiana plants, achieving a purity of 97%, a recovery
      of >95% and an initial dynamic binding capacity at 10% product breakthrough of 4
      mg mL-1 after a contact time of 2 min. The resin capacity declined to 15% of the
      starting value within 25 cycles when 1.25 M magnesium chloride was used for
      elution. We confirmed the binding activity of the 2F5 product by surface plasmon
      resonance spectroscopy. DFE is not yet optimized, and a cost analysis revealed
      that boosting DFE expression and increasing its capacity by fourfold will make
      the resin cost-competitive with some Protein A counterparts. The affinity resin
      can also be exploited to purify idiotype-specific mAbs.

PMID- 30104061
TI  - Alternatives to PumpKIN: The ongoing development of ventricular assist devices
      for infants.

PMID- 30104062
TI  - A better treatment for saphenous vein graft disease after coronary artery bypass
      surgery: Might statins be the answer at the right dose to the right patient at
      the right time?

PMID- 30104063
TI  - Long-term results of the modified Konno procedure in high-risk children with
      obstructive hypertrophic cardiomyopathy.
AB  - OBJECTIVE: Transaortic septal myectomy is the gold standard surgery in
      obstructive hypertrophic cardiomyopathy, but it is not optimal for children aged
      less than 5 years and with right ventricular outflow tract obstruction. We
      evaluated outcomes with the modified Konno procedure in children with severe
      forms of obstructive hypertrophic cardiomyopathy. METHODS: A total of 79
      consecutive children who underwent the modified Konno procedure in our center
      between 1991 and 2016 were included. RESULTS: Clinical features included age less
      than 5 years (38%), maximal septal thickness 25 mm or more (32%), extension to
      the left ventricular apex (29%), and right ventricular outflow tract obstruction
      (28%). In total, 25% of patients had Noonan syndrome. Five children (6%) aged
      less than 15 months with Noonan syndrome and biventricular obstruction died in
      the hospital. Mean follow-up was 6 +/- 5.7 years. Survival without death and
      heart transplantation was 82% at 20 years. Atrioventricular block occurred in 9
      patients (11%) and was associated with right ventricular outflow tract
      obstruction and surgery before 2010. Death, resuscitated sudden cardiac death,
      and appropriate implantable defibrillator shock were associated with maximal
      septal thickness before surgery (adjusted odds ratio, 1.20; 95% confidence
      interval, 1.07-1.35; P = .002) and need for an associated procedure (adjusted
      odds ratio, 8.84; 95% confidence interval, 2.01-38.93; P = .004). There was no
      case of recurrent obstruction. Reoperation was required in 4 patients (5%) for
      other reasons. CONCLUSIONS: The modified Konno procedure provided durable
      obstruction relief and good long-term survival in children with severe forms of
      obstructive hypertrophic cardiomyopathy. Children with Noonan syndrome undergoing
      surgery early in life were at higher risk of early mortality.

PMID- 30104064
TI  - Patient-specific, 3-dimensionally engineered silicone Y-stents in
      tracheobronchomalacia: Clinical experience with a novel type of airway stent.

PMID- 30104065
TI  - Sternal closure: Wires are still the king!

PMID- 30104066
TI  - We are the company we keep: The importance of the tumor microenvironment.

PMID- 30104067
TI  - Late results of the Ross procedure.
AB  - OBJECTIVE: The study objective was to examine the long-term results of the Ross
      procedure in a cohort of patients followed prospectively for more than 2 decades.
      METHODS: From 1990 to 2004, 212 consecutive patients with a median age
      (interquartile range) of 34 years (28-41) underwent the Ross procedure; 82% had
      congenital aortic valve disease. The technique of aortic root replacement was
      used in one half of the patients. Patients have been followed prospectively for a
      median (interquartile range) of 18.0 (14.6-21.2) years. Valve function was
      assessed by echocardiography. RESULTS: Cumulative mortality at 20 years was 10.8%
      (95% confidence interval, 6.5-17.8). Thirty patients required Ross-related
      reoperations and 3 for coronary artery disease. The cumulative probability of
      Ross-related reoperations at 20 years was 16.8% (95% confidence interval, 11.3
      24.5), on the pulmonary autograft was 11.5% (95% confidence interval, 7.2-18.0),
      and on the pulmonary homograft was 8.2% (4.6-14.7). The implantation technique
      was not associated with the cumulative incidence of reoperations on the pulmonary
      autograft. The development of moderate or severe aortic insufficiency and
      pulmonary homograft dysfunction increased with time. At 20 years, the probability
      of aortic insufficiency was 13% (95% confidence interval, 8.0-20.3) and of
      pulmonary homograft dysfunction was 19.7% (95% confidence interval, 13.9-27.2).
      Preoperative aortic insufficiency was associated with increased odds of
      postoperative aortic insufficiency. CONCLUSIONS: The long-term results of the
      Ross procedure are excellent regardless of the implantation technique, but there
      is a progressive deterioration of function of both semilunar valves.

PMID- 30104068
TI  - A better prognostic assessment of the aortic root repair with valve
      reimplantation.

PMID- 30104069
TI  - Waiting for repair: Neonatal risk for brain injury during the preoperative
      period.

PMID- 30104070
TI  - Adjuvant chemotherapy may improve prognosis after resection of stage I lung
      cancer with lymphovascular invasion.
AB  - OBJECTIVES: This study explored the prognostic significance and adjuvant
      chemotherapy benefits in resected patients with stage I non-small cell lung
      cancer with lymphovascular invasion. METHODS: A total of 2633 patients who
      received complete resection with pathologic stage I non-small cell lung cancer in
      the Shanghai Chest Hospital (2008-2012) were enrolled in the study, of whom 222
      were diagnosed with lymphovascular invasion. By using the Kaplan-Meier method and
      Cox proportional hazard regression model, we explored the impact of
      lymphovascular invasion on prognosis and determined if the use of adjuvant
      chemotherapy is associated with improved outcomes in patients with lymphovascular
      invasion. A propensity score-matched analysis was implemented to reduce the
      selection bias. RESULTS: Patients with lymphovascular invasion had an unfavorable
      overall survival and recurrence-free survival in stage I non-small cell lung
      cancer. Multivariate Cox analysis indicated that lymphovascular invasion was an
      independent poor prognostic factor for recurrence-free survival (hazard ratio
      [HR], 2.06; 95% confidence interval [CI], 1.58-2.71; P < .001) and overall
      survival (HR, 2.04; 95% CI, 1.45-2.87; P < .001) in patients with stage I. After
      using propensity score-matched pairs, analysis of 65 pairs of patients with
      lymphovascular invasion indicated a beneficial recurrence-free survival (HR,
      0.33; 95% CI, 0.16-0.67; P = .002) and overall survival (HR, 0.30; 95% CI, 0.12
      0.74; P = .009) from adjuvant chemotherapy. CONCLUSIONS: Lymphovascular invasion
      was correlated with poor prognosis in patients with stage I non-small cell lung
      cancer. For such patients, adjuvant chemotherapy was associated with improved
      survival. Our study suggests that adjuvant chemotherapy might be an appropriate
      option for patients with stage I non-small cell lung cancer with lymphovascular
      invasion.

PMID- 30104071
TI  - Comment on "Evaluation of the effectiveness and mechanisms of acetaminophen and
      methylene blue dye adsorption on activated biochar derived from municipal solid
      wastes".
AB  - This comment concern a mistake of applying pseudo-first order kinetic equation
      for adsorption systems.

PMID- 30104072
TI  - Masquerade syndrome: An eye problem as a manifestation of a more sinister
      disease.
AB  - A middle-aged man with cardiovascular risk factors, who suffered from a slight
      loss of unilateral vision for 6 months. After obtaining a diagnosis of diffuse
      choroiditis+papillitis within a probable masquerade syndrome, the patient was
      referred to outpatient Internal Medicine where this diagnosis was confirmed as an
      extended neoplastic disease.

PMID- 30104073
TI  - Transcanal endoscopic infracochlear vestibular neurectomy: A pilot cadaveric
      study.
AB  - PURPOSE: Effective operative approaches for the treatment of refractory vertigo
      in Meniere's disease are invasive. Vestibular neurectomy can preserve hearing and
      has been shown to be effective; however, current approaches require an extensive
      craniotomy. Transcanal endoscopic approaches to the internal auditory canal (IAC)
      with cochlear preservation have been recently described and may offer a minimally
      invasive approach to selectively sectioning the distal vestibular nerves while
      preserving residual hearing. MATERIALS AND METHODS: Three cadaveric human heads
      were imaged using high resolution computed tomography (CT). Anatomic analysis of
      preoperative CT scans showed adequate diameters (>3 mm) of the infracochlear
      surgical corridor for access to the IAC. A transcanal endoscopic approach was
      attempted to section the vestibular nerve. Post-operative CT scans were assessed
      to define the operative tract, determine cochlear preservation and assess
      cochlear and facial nerve preservation. RESULTS: Transcanal endoscopic approach
      was successfully performed (n = 3) using 3 mm-diameter, 14 cm-length 0 degrees ,
      30 degrees , and 45 degrees  endoscopes and microsurgical drills. In all cases
      the tympanomeatal flap and ossicular chain remained intact. Internal auditory
      canalotomy was performed using angled instruments and confirmed in real time via
      lateral skull base navigation. The vestibular nerves were readily identified and
      sectioned with preservation of the facial and cochlear nerves. Post-procedure CT
      showed no violation of the cochlea. CONCLUSION: A transcanal, infracochlear
      approach to the IAC may permit a minimally invasive approach to distal vestibular
      neurectomy in cadavers with appropriate anatomy.

PMID- 30104074
TI  - Melasma in a transgender woman.

PMID- 30104075
TI  - Insulin Sensitizers Modulate GnRH Receptor Expression in PCOS Rats.
AB  - BACKGROUND: Insulin sensitizers like metformin and pioglitazone are clinically
      used since last decades for the treatment of PCOS, but their efficacy and
      possible role in PCOS patients remains questionable. Also, the mechanism by which
      these insulin sensitizers show effect is not clear. AIM OF THE STUDY: To evaluate
      the effect of metformin and pioglitazone on leutinizing hormone and follicle
      stimulating hormone receptor mRNA expression, hyperandrogenism and insulin
      resistance in high fat diet induced and letrozole induced PCOS in rats. METHODS:
      Pre-pubertal female rats were divided into four groups: group I received normal
      pellet diet and group II, III and IV received high fat diet. After 105 d of
      dietary manipulation, metformin and pioglitazone treatment was given to group III
      and group IV animals respectively for 21 d. Similarly, adult female rats were
      divided into four groups: group I received 1% carboxymethyl cellulose (CMC) and
      group II, III, IV received letrozole for 21 d. After 21 d of letrozole
      administration, metformin and pioglitazone treatment was given to group III and
      group IV animals respectively for 21 d. Oral glucose tolerance test, lipid
      profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight,
      leutinizing hormone receptor and follicle stimulating hormone receptor mRNA
      expression was measured. Polycystic ovarian morphology was assessed through
      histopathological changes of ovary. RESULTS AND CONCLUSION: Metformin and
      pioglitazone treatment improve both metabolic and reproductive parameters of PCOS
      including hyperinsulinemia and hyperandrogenism. LH receptor and FSH receptor
      mRNA expression were altered by pioglitazone and metformin treatment.

PMID- 30104076
TI  - Correlation between adenosine triphosphate (ATP)-binding cassette transporter G2
      (ABCG2) and drug resistance of esophageal cancer and reversal of drug resistance
      by artesunate.
AB  - The present study investigated the correlation between the abnormal expression of
      adenosine triphosphate (ATP)-binding cassette transporter G2 (ABCG2) in
      esophageal cancer and the drug resistance of esophageal cancer, the reversal
      effect in drug resistance of artesunate (Art), and the mechanism underlying
      esophageal cancer using nude mice with subcutaneous xenograft as an animal model.
      The gene and protein expression of ABCG2 was detected in 80 cases of esophageal
      cancer, atypical dysplasia, and normal mucosa. A subcutaneous xenograft tumor
      mouse model was established by subcutaneous inoculation of esophageal cancer cell
      line Eca109/ABCG2 into BALB/c nu/nu nude mice. The reversal of drug resistance by
      Art in esophageal cancer was studied in vivo. The mice model was injected
      intraperitoneally with Art and/or doxorubicin (ADM). The animals were divided
      into six groups: high dose Art (50 mg/kg), low dose Art (25 mg/kg), ADM (1
      mg/kg), ADM and high-dose Art, ADM and low-dose Art, and physiological saline as
      a control. ABCG2 protein expression and cellular ADM concentration were detected
      by flow cytometry. The mRNA and protein expressions of ABCG2 in esophageal cancer
      were significantly higher than that in the normal esophagus (P < 0.01). The
      volume and mass of the subcutaneously implanted tumors in the ADM+Art high- and
      low-dose groups were significantly decreased than that in the control group (P <
      0.05), while the apoptosis rate of tumor cells and the cellular concentration of
      ADM were increased significantly (P < 0.05), and the ABCG2 protein expression in
      the tumor cells decreased significantly (P < 0.05). Abnormally high expression of
      ABCG2 in esophageal cancer tissues is involved in the multidrug resistance of
      esophageal cancer. In vivo studies showed that Art could reverse the esophageal
      cancer drug resistance by regulating the ABCG2 expression in tumor cells.

PMID- 30104077
TI  - Long non-coding RNAs expression levels in diffuse large B-cell lymphoma: An in
      silico analysis.
AB  - Long non-coding RNAs (lncRNAs), are lengthy noncoding transcripts with pivotal
      roles in biological pathways including cell cycle, apoptosis and chromatin
      remodeling. Aberrant expression of lncRNAs has been strongly connected with tumor
      progression and metastasis. However, the prognostic significance of lncRNAs in
      diffuse large-B-cell lymphoma (DLBCL) remains unclear. In this study, the
      expression levels of 189 approved lncRNAs were considered in DLBCL patients using
      several different genomic and transcriptome datasets. The analyses showed that
      the lncRNA GAS5 allocated the maximum score of RNA dysregulation and can be
      considered as good choice in DLBCLs' researches.

PMID- 30104078
TI  - Plate Fixation With Cancellous Graft for Scaphoid Nonunion With Avascular
      Necrosis.
AB  - PURPOSE: Currently, there is no consensus on the optimal treatment for scaphoid
      nonunion with avascular necrosis (AVN). Various techniques, often involving
      vascularized corticocancellous bone grafting, have been proposed. The authors
      hypothesized that similar outcomes might be possible with volar plate fixation
      augmented with autogenous pure cancellous graft. METHODS: The authors performed a
      retrospective chart review of 13 cases of scaphoid nonunions with AVN in 12
      patients treated with plate fixation and pure cancellous bone grafting. Surgical
      management included a volar incision, reduction, impaction of cancellous bone
      graft from the ipsilateral olecranon and/or distal radius, and application of a
      volar locking plate. Postoperative outcome measures included time to union based
      on computed tomography, patient-reported pain and disability scores, grip
      strength, range of motion, and return to work and sports. RESULTS: The average
      patient was 32 years old (range, 17-50 years) and treated an average of 18 months
      after initial injury (range, 6-49 months). Two of 12 patients (15.7%) were
      female, 3 of 12 patients (25%) were smokers, and 5 of 12 patients (41.7%) had
      failed union with previous screw fixation. Twelve scaphoids (92.3%) were treated
      for AVN associated with a proximal pole fracture, and 1 (7.7%) for AVN proximal
      to a scaphoid waist fracture. Mean follow-up was 19.5 months (range, 12-29
      months). Union was achieved in all patients. Two scaphoids (15%) achieved union
      by 12 weeks, 7 scaphoids (54%) by 18 weeks, 2 scaphoids (15%) by 24 weeks, and 2
      scaphoids (15%) by 30 weeks (range, 8.9-28 weeks). Mean Disabilities of the Arm,
      Shoulder, and Hand score improved from 30.6 +/- 6.2 before surgery to 17.2 +/-
      6.5 after surgery. All 11 employed patients returned to work, although 3 (27.2%)
      did not return to full capacity. CONCLUSIONS: Scaphoid plate fixation and pure
      nonvascularized cancellous bone grafting for scaphoid nonunion with AVN yields
      excellent union rates and good patient-reported and functional outcomes. TYPE OF
      STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

PMID- 30104080
TI  - Reply-Letter to the Editor - About acute coronary syndromes and obesity. Small
      lessons from RESCUE.

PMID- 30104079
TI  - Feel the power: sample size and meaningful effects.

PMID- 30104081
TI  - A large retrospective database analysis comparing outcomes of intraoperative
      aberrometry with conventional preoperative planning.
AB  - PURPOSE: To evaluate differences between the absolute prediction error using an
      intraoperative aberrometry (IA) device for intraocular lens (IOL) power
      determination versus the error that would have resulted if the surgeon's
      preoperative plan had been followed. SETTING: Multiple centers in the United
      States. DESIGN: Retrospective analysis of data collected using an IA device.
      METHODS: The database information was limited according to predetermined
      inclusion/exclusion criteria. Primary endpoints included the difference between
      mean and median absolute prediction error with IA use versus preoperative
      calculation, and the percentage of cases were compared when the prediction error
      was 0.5 diopters (D) or less. RESULTS: A total of 32 189 eyes were analyzed. The
      IA mean absolute prediction error was lower than the preoperative calculation,
      0.30 D +/- 0.26 (SD) versus 0.36 +/- 0.32 D (P < .0001). The aberrometry absolute
      median prediction error was lower than the preoperative calculation, 0.24 D
      versus 0.29 D (P < .0001). There was a significantly greater percentage of eyes
      with an aberrometry absolute prediction error of 0.5 D or less than eyes with a
      preoperative absolute prediction error of 0.5 D or less (26 357 [81.9%] of 32 189
      vs. 24 437 [75.9%] of 32 189, P < .0001). In addition, in those cases in which
      power of the IOL implanted was different than the preoperatively planned IOL
      power, significantly more eyes had an aberrometry absolute prediction error of
      0.5 D or less (10 385 [81.3%] of 12 779 vs. 8794 [68.8%] of 12 779, P < .0001).
      CONCLUSIONS: In a database of more than 30 000 eyes, calculations incorporating
      IA outperformed preoperative calculations. The difference was more pronounced in
      those cases in which the preoperatively planned IOL power was different than the
      power of the IOL implanted.

PMID- 30104083
TI  - Re: Nivolumab plus Ipilimumab Versus Sunitinib in Advanced Renal-cell Carcinoma.

PMID- 30104082
TI  - Below Safety Limits, Every Unit of Glomerular Filtration Rate Counts: Assessing
      the Relationship Between Renal Function and Cancer-specific Mortality in Renal
      Cell Carcinoma.
AB  - BACKGROUND: The hypothesis that renal function could influence oncological
      outcomes is supported by anecdotal literature. OBJECTIVE: To determine whether
      estimated glomerular filtration rate (eGFR) is related to cancer-specific
      mortality (CSM) in patients who had undergone surgery for renal cell carcinoma
      (RCC). DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 3457
      patients who underwent radical (39%) or partial nephrectomy (61%) for cT1-2 RCC
      between 1990 and 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The eGFR
      was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation.
      CSM was analyzed in a multivariable competing-risk framework, estimating the
      subdistribution hazard ratio (SHR) accounting for deaths from other causes. The
      relationship between eGFR and CSM was investigated from multiple statistical
      approaches-extended Cox regression with eGFR incorporated as a time-dependent
      covariate, landmark analysis, and joint modeling. Other predictors were selected
      by competing-risk random forest method and backward elimination. RESULTS AND
      LIMITATIONS: The relationship between eGFR and CSM was graphically described by a
      linear spline, i.e. a continuous piecewise linear function with two lines joined
      by a knot. For eGFR treated as a time-dependent covariate, the knot was located
      at 65ml/min; at landmark analysis with eGFR at the baseline, 12 mo, and last
      functional follow-up, the knots were 85, 60, and 65ml/min, respectively. In
      multivariable competing-risk analysis, CSM was associated with eGFR only for
      values of eGFR below these cutoffs, with SHRs for every 10ml/min of reduction in
      eGFR of 1.25 (p=0.003), 1.16 (p=0.028), 1.44 (p=0.02), and 1.16 (p=0.042),
      corresponding to time-dependent eGFR, and eGFR at baseline, 12 mo, and last
      functional follow-up, respectively. Joint modeling confirmed these results. A
      retrospective design with inherent biases in data collection represents a
      limitation. CONCLUSIONS: In patients undergoing surgery for RCC, renal function
      should be preserved in order to improve cancer-related survival. PATIENT SUMMARY:
      The relationship between renal function and probability of dying due to renal
      cancer is complex. The present study found a correlation between glomerular
      filtration rate and cancer specific mortality that could reconsider the
      oncological role of renal function in patients undergoing surgery for renal
      cancer.

PMID- 30104084
TI  - A case of subacute combined degeneration of the spinal cord due to folic acid and
      copper deficiency.
AB  - Subacute combined degeneration of the spinal cord (SACD) is a rare neurologic
      disorder manifesting progressive symptoms of paresthesia and spastic paralysis.
      Herein we present an autopsy case of SACD caused by folic acid and copper
      deficiency. A 16-year-old male presented with gradually worsening unsteady gait,
      and bladder and rectal dysfunction. He had a medical history of T-cell acute
      lymphoblastic leukemia (T-ALL), diagnosed 1.5 years previously. The patient had
      undergone chemotherapy, including methotrexate, as well as allogeneic bone mallow
      transplantation. Laboratory tests revealed normal vitamin B12 and methylmalonic
      acid concentration, but reduced serum copper, ceruloplasmin and folic acid
      concentrations. Magnetic resonance imaging revealed symmetrical T2 signal
      hyperintensities in the posterior and lateral spinal cord. The patient was
      treated with oral copper, oral folate, and intravenous vitamin B12. A month after
      this treatment, the patient's symptoms were unchanged, and 2 months later he died
      of acute adrenal insufficiency. The pathological findings of the spinal cord were
      compatible with SACD. Because SACD is usually reversible with early treatment, it
      should be suspected in high-risk patients undergoing chemotherapy or those who
      are malnourished with characteristic symptoms of SACD, even in young patients.

PMID- 30104086
TI  - A Rare Cause of Chronic Pulmonary Embolism: Hydatid Cyst.

PMID- 30104085
TI  - Primary health care nurses' views on patients' abilities and resources to make
      choices and take decisions on health care.
AB  - Recent health reforms in many European countries have emphasised patient choice
      as a tool for patient participation, and for the improved efficiency of services.
      Little attention has been paid to experiences of the nurses in these reforms,
      even though the reforms directly concern all health care personnel and cannot be
      implemented without their contribution. This study looks at patient choice from
      the perspective of the nurses working in primary health care clinics in Finland.
      In Finnish primary care, nurses have a central role in coordinating patient care
      and advising patients. The data come from 31 interviews conducted in 17 health
      care clinics. The approach adopted in the analysis is data-driven and brings
      forth nurses' experiences in their daily work with patients. A detailed analysis
      of the nurses' responses and views was conducted with discourse analysis. While
      nurses positioned some patients as knowledgeable, able to search for information
      and make use of different services without nurses' help, some of the patients
      were positioned as those needing nurses' advice and guidance through the complex
      system of health and social care services. Nurses' positions varied from co
      actors and gate-keepers to advocates and spokespersons. In order to succeed
      future health care reforms need to take better into account the realities of
      health clinics and the grassroots-level knowledge that primary care nurses have
      on patients and clinical practices.

PMID- 30104087
TI  - Stratification by demographic and clinical data of the antibiotic susceptibility
      of Escherichia coli from urinary tract infections of the community.
AB  - AIM: To determine the patterns of antibiotic susceptibility of Escherichia coli
      strains isolated from adult patients with urinary tract infection (UTI), and to
      stratify the results by age and type of UTI to verify if there are statistically
      significant differences that can help physicians to prescribe better empirical
      antibiotherapy. DESIGN: Cross-sectional prospective study. LOCATION: Community of
      Getafe (Madrid). Primary care level. PARTICIPANTS: 100 E. coli strains, randomly
      chosen, isolated from the urine (104-105cfu/ml) of different patients from
      primary care centers in the Getafe area. MAIN MEASUREMENTS: The antibiotic
      susceptibility of the strains was evaluated and the results were stratified by
      age and type of UTI. The clinical and demographic data of the patients were
      analyzed, classifying each episode as complicated UTI or uncomplicated UTI.
      RESULTS: Strains isolated from patients with uncomplicated UTI showed
      significantly greater susceptibility than those of complicated UTI to amoxicillin
      (65.9% vs. 30.6%, p=0.001), amoxicillin/clavulanic acid (95.5% vs. 77.6%,
      p=0.013) and ciprofloxacin (81.8% vs. 63.3%, p=0.047). In complicated UTI,
      susceptibility to ciprofloxacin was significantly greater in the <=65 years age
      group compared to the older age group (78.3% vs. 50%, respectively, p=0.041). In
      the rest of antibiotics, no statistically significant differences were obtained
      when comparing by age (<=65 years versus >65 years), both in uncomplicated and
      complicated UTI. CONCLUSIONS: Clinical and demographic data of patients with UTI
      are of great importance in the results of the antibiotic susceptibility in E.
      coli. Antibiograms stratified by patient characteristics may better facilitate
      empirical antibiotic selection for UTI in primary care.

PMID- 30104088
TI  - Evaluation of pleurodesis by poly-epsilon-caprolactone (PCL) gel in an animal
      model using New Zealand white rabbits.
AB  - BACKGROUND/PURPOSE: Pleurodesis with biomaterial implant is an emerging treatment
      method for pleural diseases. However, the ideal biomaterial or the optimal form
      for the common diseases is still under investigation. In our previous study, Poly
      epsilon-caprolactone (PCL) membrane produces significant pleurodesis in New
      Zealand White rabbit animal models. METHODS: We investigate the Poly-epsilon
      caprolactone (PCL) gel pleurodesis by animal models using New Zealand White
      rabbits, which were sacrificed for examination after one month. Thirty-Six New
      Zealand White rabbits were randomized into three groups equally to undergo
      procedures. Gross pleurodesis scoring was evaluated. Additionally, inflammation
      and fibrosis scoring were done under microscopic evaluation, as well as Western
      blot analysis. RESULTS: Gross evaluation of pleurodesis score revealed that lower
      concentrated PCL gel (10%) produced moderate pleural adhesion, while higher
      concentrated PCL gel (25%) showed significantly higher pleurodesis scores. (P <
      0.05) Control group with thoracostomy alone produced almost no pleurodesis (P <
      0.05). Western blot showed fibronectin expression was more evident in the 25% PCL
      gel than 10% one. CONCLUSION: PCL gel induced significant degree of pleurodesis
      in the rabbits. The 25% PCL gel produces more intensive adhesion than 10% one.
      Fibronectin plays an important role in the process of pleurodesis. Further study
      is required for the clinical application of the promising biomaterial with gel
      form.

PMID- 30104089
TI  - Editor's Choice - Systematic Review and Meta-Analysis of the Outcome of Treatment
      for Type II Endoleak Following Endovascular Aneurysm Repair.
AB  - OBJECTIVES: The efficacy and need for secondary interventions for type II
      endoleaks following endovascular abdominal aortic aneurysm repair (EVAR) remain
      controversial. This systematic review aimed at investigating the clinical
      outcomes of different type II endoleak treatments in patients with a persistent
      type II endoleak after EVAR. DATA SOURCES: Embase, Medline via Ovid, Web of
      Science Core Collection, the Cochrane CENTRAL, and Google Scholar. REVIEW
      METHODS: This systematic review was performed in accordance with the PRISMA
      Statement. Outcomes of interest were technical and clinical success, change in
      sac diameter, complications, need for additional interventions, abdominal aortic
      aneurysm (AAA) rupture, and (AAA related) mortality. Meta-analyses were performed
      with random effects models. RESULTS: A total of 59 studies were included, with a
      cumulative cohort of 1073 patients with persistent type II endoleak. Peri
      operative complications following treatment of type II endoleaks occurred in 3.8%
      of patients (95% CI 2.7-5.2%), and AAA related mortality was 1.8% (95% CI 1.1
      2.7%). Overall technical success was 87.9% (95% CI 83.1-92.1%), while clinical
      success was 68.4% (95% CI 61.2-75.1%). Among studies detailing sac dynamics,
      decrease or stable sac, with or without resolution, was achieved in 78.4% (95% CI
      70.2-85.6%). Changes in sac diameter following type II endoleak treatment were
      documented in 157 patients to at least 24 months. Within this group an actual
      decrease in sac diameter was reported in only 27 of 40 patients. CONCLUSION:
      There is little evidence supporting the efficacy of secondary intervention for
      type II endoleaks after EVAR. Although generally safe, the lack of evidence
      supporting the efficacy of type II endoleak treatment leads to difficulty in
      assessing its merits.

PMID- 30104090
TI  - Communication and bed reservation: Decreasing the length of stay for emergency
      department trauma patients.
AB  - BACKGROUND: Prolonged emergency department (ED) length of stay (LOS) is
      associated with poorer clinical outcomes and patient experience. At our community
      hospital, trauma patients were experiencing extended ED LOS incommensurate with
      their clinical status. Our objective was to determine if operational
      modifications to patient flow would reduce the LOS for trauma patients. METHOD:
      We conducted a retrospective chart review of admitted trauma patients from
      January 1, 2015 to June 30, 2016 to study two interventions. First, a
      communication intervention [INT1], which required the ED provider to directly
      notify the trauma service, was studied. Second, a bed intervention [INT2], which
      reserved two temporary beds for trauma patients, was added. The primary outcome
      was the average ED LOS change across three time periods: (1) Baseline data [BASE]
      collected from January 1, 2015 to June 30, 2015, (2) INT1 data collected from
      July 1, 2015 to October 18, 2015, and (3) INT2 data collected from October 19,
      2015 to June 30, 2016. Data was analyzed using descriptive statistics, two-sample
      t-tests, and multivariate linear regression. RESULTS: A total of 777 trauma
      patients were reviewed, with 151, 150 and 476 reviewed during BASE, INT1, and
      INT2 time periods, respectively. BASE LOS for trauma patients was 389 min. After
      INT1, LOS decreased by 74.35 min (+/-31.92; p < 0.0001). After INT2 was also
      implemented, LOS decreased by 164.56 min (+/-22.97; p < 0.0001) from BASE LOS.
      CONCLUSION: Direct communication with the trauma service by the ED provider and
      reservation of two temporary beds significantly decreased the LOS for trauma
      patients.

PMID- 30104091
TI  - Laryngopyocele: A deep neck infection diagnosed by emergency ultrasound.
AB  - Laryngopyocele is a rare diagnosis that can cause life-threating conditions such
      as airway obstruction and even death. Emergency ultrasound (POCUS) can be very
      helpful during the diagnosis and monitoring of the illness because it is both
      easy to apply and repeatable. A deep neck infection was diagnosed as
      laryngopyocele by POCUS in the emergency department; this is the first case in
      the literature.

PMID- 30104092
TI  - The DAGMAR Score: D-dimer assay-guided moderation of adjusted risk. Improving
      specificity of the D-dimer for pulmonary embolism.
AB  - We generated a novel scoring system to improve the test characteristics of D
      dimer in patients with suspected PE (pulmonary emboli). Electronic Medical Record
      data were retrospectively reviewed on Emergency Department (ED) patients 18 years
      or older for whom a D-dimer and imaging were ordered between June 4, 2012 and
      March 30, 2016. Symptoms (dyspnea, unilateral leg swelling, hemoptysis), age,
      vital signs, medical history (cancer, recent surgery, medications, history of
      deep vein thrombosis or PE, COPD, smoking), laboratory values (quantitative D
      dimer, platelets, and mean platelet volume (MPV)), and imaging results (CT, VQ)
      were collected. Points were designated to factors that were significant in two
      multiple regression analyses, for PE or positive D-dimer. Points predictive of PE
      were designated positive values and points predictive of positive D-dimer,
      irrespective of presence of PE, were designated negative values. The DAGMAR (D
      dimer Assay-Guided Moderation of Adjusted Risk) score was developed using age and
      platelet adjustment and points for factors associated with PE and elevated D
      dimer. Of 8486 visits reviewed, 3523 were unique visits with imaging, yielding
      2253 (26.5%) positive D-dimers. 3501 CT scans and 156 VQ scans were completed,
      detecting 198 PE. In our cohort, a DAGMAR Score < 2 equated to overall PE risk <
      1.2%. Specificity improved (38% to 59%) without compromising sensitivity (94% to
      96%). Use of the DAGMAR Score would have reduced CT scans from 2253 to 1556 and
      lead to fewer false negative results. By considering factors that affect D-dimer
      and also PE, we improved specificity without compromising sensitivity.

PMID- 30104094
TI  - A comparison of induced effects on urinary calcium by thiazides and different
      dietary salt doses: Implications in clinical practice.
AB  - INTRODUCTION: Both dietary restriction of sodium chloride (NaCl) and treatment
      with thiazides have been used in hypercalciuric patients. OBJECTIVES: To
      calculate regular salt intake and investigate the correlation between natriuresis
      and urinary calcium with usual diet (B) and after changing the amount of NaCl
      intake and administration of thiazides. MATERIAL AND METHODS: Nineteen healthy
      young individuals had their diet replaced by 2l of Nutrison(r) Low Sodium (500mg
      sodium/day) daily for two days. Then, 5g of NaCl were added every two days ("5",
      "10" and "15"), administering 50mg (H50) and 100mg (H100) of Higroton(r) on the
      last two days. Blood sodium, plasma renin activity (PRA) and aldosterone were
      determined in venous blood samples, as were urinary sodium and calcium.
      STATISTICAL ANALYSIS: Wilcoxon t-test and the Pearson linear correlation were
      calculated. RESULTS: Urinary Na (mEq/24h): 210.3+/-87.6 ("B"); 42.7+/-20.4 ("5");
      135.5+/-50.6 ("10"); 225.5+/-56.7 ("15"). Urinary calcium (mg/24h): 207.8+/-93.6
      ("B"); 172.8+/-63.1 ("5"); 206.2+/-87.7 ("10"); 227.4+/-84.1 ("15"). A positive
      correlation was observed between natriuresis and urinary calcium in "10" (r=0.47)
      and "15" (r=0.67). After Higroton(r), natriuresis: 232.3+/-50.7; 377+/-4 (H50);
      341.1+/-68.4 (H100); Ca in urine: 209.8+/-57.4; 213.2+/-67.6 (H50); 159.1+/-52.2
      (H100). CONCLUSIONS: Salt intake in the population studied was estimated to be
      14.9+/-4.9g/day with a positive correlation found between sodium and calcium
      urine output with daily intakes of 11.25 and 16.25g of salt. With the usual
      intake, for each gram of salt, urinary calcium increased by 5.46 mg/24 h and with
      100mg of Higroton(r) it decreased by 50.7mg/24h. These data could be useful for
      the management of patients with excretory hypercalciuria or hypoparathyroidism.

PMID- 30104093
TI  - 2,4-Diamino-6-methylpyrimidines for the potential treatment of Chagas' disease.
AB  - Chagas' disease, caused by the protozoan parasite Trypanosoma cruzi, affects 8-10
      million people across the Latin American population and is responsible for around
      12,500 deaths per annum. The current frontline treatments, benznidazole and
      nifurtimox, are associated with side effects and lack efficacy in the chronic
      stage of the disease, leading to an urgent need for new treatments. A high
      throughput screening campaign against the physiologically relevant intracellular
      form of the parasite identified a series of 2,4-diamino-6-methylpyrimidines.
      Demonstrating the series did not work through the anti-target TcCYP51, and was
      generally cytocidal, confirmed its suitability for further development. This
      study reports the optimisation of selectivity and metabolic stability of the
      series and identification of a suitable lead for further optimisation.

PMID- 30104095
TI  - Aldosteronism with elevated active renin concentration: Primary versus secondary?
      Importance of follow-up for the diagnosis.

PMID- 30104096
TI  - Reversible secretome and signaling defects in diabetic mesenchymal stem cells
      from peripheral arterial disease patients.
AB  - OBJECTIVE: Regenerative medicine seeks to stall or to reverse the pathologic
      consequences of chronic diseases. Many people with diabetes have peripheral
      arterial disease (PAD), which increases their already high risk of major
      amputation. Cellular therapies are a promising regenerative medicine approach to
      PAD that can be used to focally inject regenerative cells to endangered tissue
      beds. Mesenchymal stem cells (MSCs) are known to promote tissue regeneration
      through stromal support and paracrine stimulation of new blood vessels
      (angiogenesis). Whereas little is known about human diabetic MSCs (dMSCs),
      particularly those from patients with PAD, dMSCs have a limited expansion
      capacity but can be improved with human platelet lysate (PL) supplementation. PL
      is rich in many growth factors, including epidermal growth factor (EGF), which is
      known to be important to cell proliferation and survival signaling pathways. We
      hypothesize that dMSCs have a reversible defect in EGF receptor pathways. The
      objective of this work was to test this hypothesis using dMSCs from PAD patients.
      METHODS: The secretome expression of EGF and prominent angiogens was
      characterized from bone marrow (BM)-derived and adipose tissue-derived (ATD)
      dMSCs from five patients (six limbs) undergoing major amputation. Western blot
      was used to characterize the AKT and extracellular signal-regulated protein
      kinases 1 and 2 expression in dMSCs under standard culture (5% fetal bovine serum
      plus fibroblast growth factor 2 [FGF2]), 5% human PL, or 5% fetal bovine serum
      plus EGF. Healthy donor MSCs were control cells. The angiogenic activity of BM-
      and ATD-dMSCs was tested on human umbilical vein endothelial cells (ECs). Paired
      t-test, analysis of variance, and Kruskal-Wallis tests were used as appropriate.
      RESULTS: Both BM- and ATD-dMSCs had typical MSC surface marker expression and
      similar expansion profiles, and they did not express EGF in their secretome. PL
      supplementation of dMSCs improved AKT signaling, but they were resistant to FGF2
      activation of extracellular signal-regulated protein kinases 1 and 2. EGF
      supplementation led to similar AKT expression as with PL, but PL had greater
      phosphorylation of AKT at 30 and 60 minutes. The conditioned media from both BM-
      and ATD-dMSCs had robust levels of prominent angiogens (vascular endothelial
      growth factor, monocyte chemoattractant protein 1, hepatocyte growth factor),
      which stimulated EC proliferation and migration, and the co-culture of dMSCs with
      ECs led to significantly longer EC sprouts in three-dimensional gel than EC-alone
      pellets. CONCLUSIONS: PL and EGF supplementation improves AKT expression in dMSCs
      over that of FGF2, but PL improved pAKT over that of EGF. Thus, PL
      supplementation strategies may improve AKT signaling, which could be important to
      MSC survival in cellular therapies. Furthermore, BM- and ATD-dMSCs have similar
      secretomes and robust in vitro angiogenic activity, which supports pursuing dMSCs
      from both reservoirs in regenerative medicine strategies.

PMID- 30104097
TI  - Early results with the custom-made Fenestrated Anaconda aortic cuff in the
      treatment of complex abdominal aortic aneurysm.
AB  - OBJECTIVE: The objective of this study was to investigate the feasibility of a
      specific custom-made fenestrated aortic cuff in the treatment of complex
      abdominal aortic aneurysms (AAAs). METHODS: Between 2013 and 2016, a total of 57
      custom-made Fenestrated Anaconda (Vascutek, Inchinnan, Scotland, UK) aortic cuffs
      were placed in 38 centers worldwide. All centers were invited to participate in
      this retrospective analysis. Postoperative and follow-up data included the
      presence of adverse events, necessity for reintervention, and renal function.
      RESULTS: Fifteen clinics participated, leading to 29 cases. Median age at
      operation was 74 years (interquartile range [IQR], 71-78 years); five patients
      were female. Two patients were treated for a para-anastomotic AAA after open AAA
      repair, 19 patients were treated because of a complicated course after primary
      endovascular AAA repair, and 8 cases were primary procedures for AAA. A total of
      76 fenestrations (mean, 2.6 per case) were used. Four patients needed seven
      adjunctive procedures. Two patients underwent conversion, one because of a
      dissection of the superior mesenteric artery and one because of perforation of a
      renal artery. Median operation time was 225 minutes (IQR, 150-260 minutes);
      median blood loss, 200 mL (IQR, 100-500 mL); and median contrast volume, 150 mL
      (IQR, 92-260 mL). Primary technical success was achieved in 86% and secondary
      technical success in 93%. The 30-day morbidity was 7 of 29 with a mortality rate
      of 4 of 29. Estimated glomerular filtration rate remained unchanged before and
      after surgery (76 to 77 mL/min/m2). Between preoperative and median follow-up of
      11 months, estimated glomerular filtration rate was reduced statistically
      significantly (76 to 63 mL/min/m2). During follow-up, 9 cases had an increase in
      aneurysm sac diameter (5 cases >5 mm); 14 cases had a stable or decreased
      aneurysm sac diameter; and in 2 cases, no aneurysm size was reported. No type I
      endoleak was reported, and two cases with a type III endoleak were treated by
      endovascular means during follow-up. Survival, reintervention-free survival, and
      target vessel patency at 1 year were 81% +/- 8%, 75% +/- 9%, and 99% +/- 1%,
      respectively. After 2 years, these numbers were 81% +/- 8%, 67% +/- 11%, and 88%
      +/- 6%, respectively. During follow-up, the two patients with a type III endoleak
      needed endograft-related reinterventions. CONCLUSIONS: Treatment with this
      specific custom-made fenestrated aortic cuff is feasible after complicated
      previous (endovascular) aortic repair or in complex AAAs. The complexity of
      certain AAA cases is underlined in this study, and the Fenestrated Anaconda
      aortic cuff is a valid option in selected cases in which few treatment options
      are left.

PMID- 30104098
TI  - Outcome of drug-eluting balloon angioplasty versus endarterectomy in common
      femoral artery occlusive disease.
AB  - OBJECTIVE: Common femoral artery (CFA) occlusive disease remains a debatable site
      for endovascular therapy, and the outcome of drug-eluting balloon (DEB)
      angioplasty in treating CFA occlusive disease is largely unknown. This study
      compared the efficacy, safety, and short-term patency rate of DEB angioplasty and
      femoral endarterectomy for treatment of CFA occlusive disease. METHODS: From
      March 2013 to June 2016, there were 100 patients with symptomatic CFA occlusive
      disease who were retrospectively reviewed. Forty patients were treated with DEB
      angioplasty and 60 were treated with femoral endarterectomy. Each patient
      received regular follow-up. Patency rate, ankle-brachial index, target lesion
      revascularization, and adverse events were assessed. RESULTS: Technical success
      was 100% in all patients. The DEB group had a lower 1-year primary patency rate
      (75.0% vs 96.7%; P = .003), but the secondary patency rate was similar between
      the two groups (97.5% vs 98.3%; P = 1.000). At 2-year follow-up, the primary
      patency was lower in the DEB group (57.1%) than in the endarterectomy group
      (94.1%; P = .001), whereas the secondary patency rate had no significant
      difference (90.5% vs 97.1%; P = 1.000). Both groups had significant improvement
      in ankle-brachial index. Freedom from target lesion revascularization was lower
      in the DEB group both at 1 year (75.0% vs 96.7%; P = .003) and at 2 years (57.1%
      vs 94.1%; P = .001). There was no significant difference in the incidence of
      complications and adverse events. CONCLUSIONS: Femoral endarterectomy has a
      better primary patency rate compared with DEB angioplasty in treating CFA
      occlusive disease without significant increase in complications. In patients not
      suitable for endarterectomy, DEB angioplasty provides a similar secondary patency
      rate and could be considered an alternative treatment.

PMID- 30104099
TI  - Outcome of intramedullary pinning of isolated radial neck fractures in adulthood.
AB  - BACKGROUND: The treatment of radial neck fractures is controversial and typically
      depends on displacement. Surgical procedures based on open reduction-internal
      fixation (ORIF) may lead to several complications, such as avascular necrosis of
      the radial head, nonunion, malunion, and elbow stiffness. Closed reduction with
      intramedullary pinning of radial neck fractures, which is commonly used in
      children, is a viable option for these fractures in adults and may allow for a
      lower complication rate compared with ORIF. The aim of this study was to report
      the functional outcome of closed reduction and intramedullary stabilization in
      isolated radial neck fractures. METHODS: Fourteen cases were retrospectively
      reviewed between January 2007 and December 2016. The inclusion criteria were
      isolated radial neck fractures of type I to III according to the Mason
      classification, absence of previous injuries of the elbow, and a minimum of 1
      year of follow-up. The Mason classification was used to classify these injuries.
      At final follow-up, functional assessment was established based on functional
      scores: Morrey Elbow Score, Elbow Self-Assessment Score, and QuickDASH (short
      version of Disabilities of the Arm, Shoulder and Hand questionnaire) score. Range
      of motion was evaluated similarly. RESULTS: The mean follow-up period was 86
      months. The mean age was 44.2 years. Regarding the functional outcome, 78% of
      patients claimed satisfaction. Concerning the functional scoring, the mean visual
      analog scale score was 0.2 (range, 0-4) and the mean Morrey Elbow Score was 95.7
      (range, 85-100). The mean QuickDASH score was 6.4 (range, 7-22). The complication
      rate was 35%. Malunion was observed in 7% of patients. CONCLUSION: Intramedullary
      pinning of radial neck fractures represents a viable technique in adults because
      of its safety and simplicity. The complication rates are lower than those in
      other reports of ORIF.

PMID- 30104100
TI  - The effect of stemless humeral component fixation feature design on bone stress
      and strain response: a finite element analysis.
AB  - BACKGROUND: Since the advent of stemless implants, several different fixation
      feature designs have been used to improve primary implant stability. These
      stemless designs are diverse, and the rationale for their selection and design
      has not been thoroughly studied. Accordingly, this investigation assessed the
      effect of stemless implant geometry on the simulated stress and strain response
      of the proximal humerus. METHODS: Five humeral finite element models were used to
      examine 10 generic stemless implants with variable fixation features (2 central,
      4 peripheral, and 4 boundary crossing). Loads representing 45 degrees  and 75
      degrees  of shoulder abduction were simulated. Implants were compared based on
      the percentage of implant-bone surface area that remained in contact, the change
      in bone stress relative to the intact state, and the simulated potential for bone
      to resorb, remodel, or remain unchanged after reconstruction. RESULTS: The
      implant-bone contact area was greatest for peripheral, followed by central and
      boundary-crossing designs. All implants elicited similar bone stress variations,
      which were greatest 0 to 5 mm beneath the resection and laterally. The simulated
      potential cortical response was also similar for all implants, with the greatest
      simulated resorbing potential 0 to 15 mm beneath the resection, and very little
      expected remodeling. Differences between implants were most prominent within the
      simulated potential trabecular response, with the central implants having the
      least bone volume percentage expected to resorb. CONCLUSIONS: Simulated humeral
      bone response after stemless anatomic shoulder replacement depends on fixation
      feature geometry. Trade-offs exist between implant types. Centrally pegged
      implants produced the lowest simulated resorbing potential, whereas peripheral
      implants had the greatest percentages of implant-bone contact area.

PMID- 30104101
TI  - One-stage exchange of septic shoulder arthroplasty following a standardized
      treatment algorithm.
AB  - BACKGROUND: Studies on 1-stage exchange in septic shoulder arthroplasty are
      limited and show a wide variation of treatment strategies. This retrospective
      study investigated infection-free survival and function of 1-stage exchange of
      septic shoulder arthroplasty following a standardized treatment algorithm.
      METHODS: The requirement for 1-stage exchange was an isolated microorganism from
      synovial fluid aspiration or synovial biopsy with an antibiotic susceptibility
      profile prior to revision surgery. If no microorganism was isolated or the
      underlying pathogen was a difficult-to-treat microorganism (not accessible for
      biofilm-active antibiotics, enterococci, and fungi), 2-stage exchange was
      performed. Function was assessed by the Constant score. RESULTS: Fourteen
      patients were included, with a mean follow-up period of 5.8 years. The most and
      second most commonly detected microorganisms were Cutibacterium acnes (formerly
      Propionibacterium acnes), and Staphylococcus epidermidis, respectively. At 1
      stage exchange, patients received local and systemic antibiotics based on the
      susceptibility profile of the microorganism. Twelve patients with insufficient
      rotator cuffs received reverse shoulder arthroplasty, whereas 2 patients with
      intact rotator cuffs underwent anatomic total shoulder arthroplasty. The
      infection-free survival rate at 1 and 5 years was 100% and 93% (95% confidence
      interval [CI], 59%-99%), respectively, with 1 recurrence of infection 22 months
      after 1-stage exchange. Another patient with limited range of motion underwent
      revision 6 months postoperatively, leading to a revision-free survival rate of
      93% (95% CI, 59%-99%) and 86% (95% CI, 54%-96%) at 1 and 5 years, respectively.
      The mean Constant score was 65 (range, 44-95). CONCLUSION: One-stage exchange
      with prior detection of the underlying microorganism provides satisfactory
      infection-free survival and function.

PMID- 30104102
TI  - Differentiation of spinal myxopapillary ependymomas from schwannomas by contrast
      enhanced MRI.
AB  - BACKGROUND: Spinal myxopapillary ependymomas (MPEs) and schwannomas (SCHs) are
      both frequently located at the conus and caudal regions. The differentiation
      between MPEs and SCHs before surgery is crucial. Signal patterns of MPEs and SCHs
      on T2-weighted (T2W) magnetic resonance imaging (MRI) are diverse. Gadolinium
      (Gd+)-enhanced areas in MRI scans areas are areas where tumor cells are abundant.
      Therefore, investigating these enhanced areas should facilitate the
      differentiation. This study aimed to evaluate Gd+ areas in MRI scans in spinal
      MPEs and SCHs. Furthermore, the relation between MRI pattern and pathological
      features was investigated. METHODS: In total, 41 patients with spinal MPEs (n =
      7) or SCHs (n = 34) around the conus medullaris were included. SCHs were
      classified per the Gd+ area of the tumor on T1-weighted (T1W) contrast images,
      into Gd+ areas with T2W hyperintensity (Gd+/T2high) (n = 4, 11.8%) or Gd+ areas
      with T2W isointensity (Gd+/T2iso) (n = 30, 88.2%). Four patients with Gd+/T2iso
      were selected randomly for comparison. In three patient groups, T2 values at the
      Gd+ area and tumor cell density as measured by HE stains (cell density) were
      compared. RESULTS: T2 values at the Gd+ area was higher in patients with MPE than
      in those with SCH with Gd+/T2high, and significantly higher than that in patients
      with SCH with Gd+/T2iso. Cell density was significantly lower in patients with
      MPEs than for those with SCHs with Gd+/T2high, and those with SCHs with
      Gd+/T2iso. CONCLUSION: The evaluation of the Gd+ area proved useful because it
      excludes cysts or necrotic portions. If the Gd+ area is hyperintense on T2WI,
      MPEs can be suspected. If the Gd+ area is isointense on T2WI, SCHs can be
      suspected. There were several exceptional cases of SCH with a Gd+ area that was
      hyperintense on T2WI. This could be explained by pathological findings showing
      low cell density, as is typical for MPEs.

PMID- 30104103
TI  - Modification of the Unified Classification System for periprosthetic femoral
      fractures after hip arthroplasty.
AB  - BACKGROUND: The Unified Classification System (UCS) for Periprosthetic femoral
      fractures (PPFF) still has some limitations. METHODS: We retrieved 18 previous
      classifications for PPFF based on systematic review of the literature, and also
      retrospectively analyzed 402 cases with PPFF. 46 cases (11.4%) were identified as
      beyond the classification scope of the original UCS. RESULTS: We modified the UCS
      as follows: (1) add two new B2 subtypes: B2PALT/B2PAGT (i.e., the pseudo ALT/AGT:
      Fracture in trochanter region including a segment of the proximal medial/lateral
      femoral cortex); (2) add a new FS category to encompass stem fracture alone or
      accompanied by PPFF, with FSO designating this fracture with stem fracture alone,
      FS1 designating this fracture with the proximal portion of the fractured femoral
      prosthesis being stable, FS2 designating this fracture with the proximal portion
      of the fractured femoral prosthesis being loose and the surrounding bone quality
      being good, and FS3 designating this fracture with the proximal portion of the
      fractured femoral prosthesis being loose and the bone bed being of poor quality;
      and (3) delete Type F which does not apply to the femur. Thus, using our
      modification of the UCS, among the 46 cases, we found thirty-five B2PALT, two
      B2PAGT, three FSO, one FS1, two FS2 and three SF3. CONCLUSIONS: Compared to the
      original UCS, our modified version is more comprehensive. We believe it is useful
      to improve the judgment of the implant stability, and establish the therapeutic
      strategy for PPFF.

PMID- 30104104
TI  - A special light-aerobic condition for photosynthetic bacteria-membrane bioreactor
      technology.
AB  - The combined photosynthetic bacteria (PSB) and membrane bioreactor (MBR)
      technology has the great advantage of simultaneously realizing wastewater
      purification and bio-resource recovery and has attracted increasing attention in
      recent years. Light-oxygen conditions are the most vital factor in wastewater
      treatment. The special light-aerobic condition was first applied to PSB-MBR
      wastewater treatment, and it was compared with three typical light-oxygen
      conditions. The results showed that the highest chemical oxygen demand (COD)
      removal efficiency (96.28%) and the highest biomass production (1.12 g/L/d) were
      simultaneously obtained under light-aerobic condition. This phenomenon overcame
      the limitations whereby optimal pollutant removal and bio-resource recovery could
      not be achieved at the same time. An analysis of the microbial community showed
      that different light-oxygen conditions caused large variations in the microbial
      community composition of PSB-MBR. The microbial diversity was lower when light
      and oxygen co-existed.

PMID- 30104105
TI  - Corrigendum to "Contemporary hydrogen deuterium exchange mass spectrometry" [144
      (2018) 27-42].

PMID- 30104106
TI  - Transesophageal Echocardiography for Pulmonary Artery Catheter Placement:
      Precision Matters.

PMID- 30104107
TI  - Circulating follicular helper T cells exhibit reduced ICOS expression and
      impaired function in narcolepsy type 1 patients.
AB  - Despite genetic and epidemiological evidence strongly supporting an autoimmune
      basis for narcolepsy type 1, the mechanisms involved have remained largely
      unknown. Here, we aimed to investigate whether the frequency and function of
      circulating follicular helper and follicular regulatory T cells are altered in
      narcolepsy type 1. Peripheral blood mononuclear cells were collected from 32
      patients with narcolepsy type 1, including 11 who developed disease after
      Pandemrix(r) vaccination, and 32 age-, sex-, and HLA-DQB1*06:02-matched healthy
      individuals. The frequency and phenotype of the different circulating B cell and
      follicular T cell subsets were examined by flow cytometry. The function of
      follicular helper T cells was evaluated by assessing the differentiation of naive
      and memory B cells in a co-culture assay. We revealed a notable increase in the
      frequency of circulating B cells and CD4+CXCR5+ follicular T cells in narcolepsy
      patients compared to age-, sex- and HLA-matched healthy controls. However, the
      inducible T-cell costimulator molecule, ICOS, was selectively down-regulated on
      follicular T cells from patients. Reduced frequency of activated ICOS+ and
      PD1high blood follicular T cells was also observed in the narcolepsy group.
      Importantly, follicular T cells isolated from patients with narcolepsy type 1 had
      a reduced capacity to drive the proliferation/survival and differentiation of
      memory B cells. Our results provide novel insights into the potential involvement
      of T cell-dependent B cell responses in the pathogenesis of narcolepsy type 1 in
      which down-regulation of ICOS expression on follicular helper T cells correlates
      with their reduced function. We hypothesize that these changes contribute to
      regulation of the deleterious autoimmune process after disease onset.

PMID- 30104108
TI  - Anti-oxidative effects of 17 beta-estradiol and genistein in human skin
      fibroblasts and keratinocytes.
AB  - BACKGROUND: Estrogens and phytoestrogens can hinder the aging process through
      mechanisms related to estrogen receptors (ERs), guanine nucleotide-binding
      protein-coupled receptor (GPER30), mitochondria function and nitric oxide (NO)
      release. Up to date, however, the above issues are a matter of debate. OBJECTIVE:
      To examine the effects elicited by 17 beta-estradiol and genistein against
      peroxidation in human keratinocytes/fibroblasts and evaluate the role played by
      ERs, GPER30, mitochondria and NO. METHODS: Human fibroblasts/keratinocytes,
      either subjected to peroxidation or not, were exposed to 17 beta
      estradiol/genistein in the absence or presence of the NO synthase (NOS)
      inhibitor, the ERs and GPER30 blockers, fulvestrant and G15, the phosphatidyl
      inositol-3-kinase (PI3K-Akt), the p38 mitogen-activated protein (MAP) kinase and
      the extracellular signal-regulated kinases (ERK) 1/2 inhibitors. Specific kits
      were used for cell viability, NO, ROS and glutathione (GSH) detection and
      mitochondrial membrane potential measurement. Western Blot analysis was performed
      for kinases expression/activation detection. RESULTS: In physiological and
      peroxidative conditions, 17 beta-estradiol/genistein respectively increased and
      reduced NO release by fibroblasts/keratinocytes. Moreover, both agents prevented
      the ROS release and the fall of cell viability and mitochondrial membrane
      potential, while increasing GSH levels and the proliferation rate. Fulvestrant
      and G15 counteracted all above responses. Also, the NOS, and the kinases blockers
      reduced the protection exerted by 17 beta-estradiol/genistein on cell
      viability/mitochondria function. The involvement of PI3K-Akt and p38-MAPK was
      confirmed by Western blot. CONCLUSION: 17 beta-estradiol/genistein protected
      fibroblasts/keratinocytes against peroxidation by modulating oxidant/antioxidant
      system and mitochondria membrane potential, through mechanisms related to ERs and
      GPER30 and kinases activation.

PMID- 30104109
TI  - A Twenty-Year Retrospective Diagnosis of Congenital Cytomegalovirus Infection.

PMID- 30104110
TI  - The Radiologically Isolated Syndrome: An Opportunity to Prevent Multiple
      Sclerosis in Children.

PMID- 30104111
TI  - Management of high risk cardiac conditions in pregnancy: Anticoagulation, severe
      stenotic valvular disease and cardiomyopathy.
AB  - Cardiovascular disease contributes to approximately one third of all maternal
      mortality and remains a significant source of peri- and postpartum morbidity. As
      more women at risk for and with cardiovascular disease are desiring pregnancy, it
      is imperative that general cardiologists and obstetricians participate
      collaboratively in preconception counseling and are more facile with management
      of these lesions during peri- and postpartum periods. This review aims to address
      this growing need and highlights the management strategies for some of the major
      high risk cardiac conditions encountered during pregnancy including
      anticoagulation, cardiomyopathies as well as severe mitral and aortic stenosis;
      aortopathy, pulmonary hypertension, and severe congenital heart lesions will not
      be addressed.

PMID- 30104112
TI  - Transgenerational Epigenetic Mechanisms in Adipose Tissue Development.
AB  - An adverse nutritional environment during the perinatal period increases the risk
      of adult-onset metabolic diseases, such as obesity, which may persist across
      generations. Adipose tissue (AT) from offspring of malnourished dams has been
      shown to display altered adipogenesis, lipogenesis, and adipokine expression,
      impaired thermogenesis, and low-grade inflammation. Although the exact mechanisms
      underlying these alterations remain unclear, epigenetic processes are believed to
      have an important role. In this review, we focus on epigenetic mechanisms in AT
      that may account for transgenerational dysregulation of adipocyte formation and
      adipose function. Understanding the complex interactions between maternal diet
      and epigenetic regulation of the AT in offspring may be valuable in improving
      preventive strategies against the obesity pandemic.

PMID- 30104113
TI  - Varicella breakthrough infection and effectiveness of 2-dose varicella vaccine in
      China.
AB  - BACKGROUND: 2-dose varicella vaccination has been available in Ningbo city, China
      since 2014 in the private sector. This study aimed to evaluate the breakthrough
      varicella infection rate, and to examine overall and incremental effectiveness of
      2-dose varicella vaccination among Chinese children. METHODS: A retrospective
      investigation was done among native children born from 2008 to 2013 in active
      surveillance area in Ningbo, China. Between 2009 and 2016, demographic
      information and data on varicella vaccination were collected by Ningbo's
      Immunization Information System, and information of varicella infections were
      obtained from China Information System for Disease Control and Prevention. The
      logistic regression was conducted to estimate varicella vaccine effectiveness
      (VE). RESULT: A total of 107,324 local children were enrolled in the cohort
      analysis and 95.11% of these children with no varicella disease history received
      at least 1-dose varicella vaccine from 2009 to 2016. The total breakthrough
      varicella infection rate (BVR) was 0.37% for all the vaccinated children and
      0.04% for 2-dose vaccination. The annual BVR ranged from 0.01% to 0.49% for 1
      dose of varicella vaccine and from 0.01% to 0.02% for 2-dose. The infection rates
      both in the unvaccinated children and the 1-dose children were decreasing after 2
      dose vaccination implemented in 2014 (Unvaccinated: P < 0.001 for trend; 1-dose:
      P = 0.003 for trend). The VE against all varicella was 50.3% (95% CI: 39.8%
      59.0%) for 1-dose (P < 0.001) and 98.7% (95% CI: 98.1%-99.1%) for 2-dose (P <
      0.001), and the incremental VE was 97.4% (95% CI: 96.2%-98.2%) compared with 1
      dose (P < 0.001). CONCLUSION: The 2-dose regimen provided excellent protection to
      prevent all varicella, and the universal 2-dose regimen of varicella vaccine
      should be recommended to prevent the varicella disease among children in China.

PMID- 30104115
TI  - In vitro assessment of biological activity and stability of the ALVAC-HIV
      vaccine.
AB  - The first evidence in humans that a safe and effective preventive vaccine for HIV
      is possible came from the phase III HIV clinical trial RV144 in Thailand. This
      trial was based on a prime/boost combination of a recombinant canarypox vaccine
      and two glycoprotein 120 proteins (ALVAC-HIV and AIDSVAX B/E). A pivotal phase
      IIb/III trial has recently commenced in the Republic of South Africa, for which
      the infectious titer assay was applied as the quantitative release test for the
      ALVAC-HIV vaccine. The infectious titer assay measures the ability of the vaccine
      vector to infect target permissive cells, but does not indicate if the vaccine
      transgenes are expressed. We have developed a high-throughput biological activity
      assay that provides results in agreement with the infectious titer assay. This
      assay uses flow cytometry to quantify expression of ALVAC-HIV encoded proteins
      gp120 and p24 in human cells. This transgene expression is detected by two cross
      clade-reactive, biologically functional human anti-gp120 monoclonal antibodies
      isolated from clinical trial participants and a commercial mouse anti-p24
      monoclonal antibody. The relative biological activity of the vaccine test sample
      is calculated by comparison of the test sample dose-response curve against that
      of a reference standard. We show that the novel biological activity assay is
      specific, accurate, precise, stability-indicating, and robust. The assay is being
      used for characterization of ALVAC-HIV (vCP2438) product, the efficacy of which
      is being evaluated in the pivotal phase IIb/III clinical trial HVTN702. The
      biological activity assay has the potential to indicate vaccine consistency and
      quality as a complement to the infectious titer assay.

PMID- 30104114
TI  - Non-interference of Bovine-Human reassortant pentavalent rotavirus vaccine
      ROTASIIL(r) with the immunogenicity of infant vaccines in comparison with a
      licensed rotavirus vaccine.
AB  - BACKGROUND: A newly developed bovine-human reassortant pentavalent vaccine (BRV
      PV, ROTASIIL(r)) was tested for its potential effect on the immunogenicity of
      concomitantly administered EPI vaccines in infants in a randomized controlled
      study in India. METHODS: In this Phase III, multicenter, open label, randomized,
      controlled study, three doses of BRV-PV or two doses of Rotarix(r) and one dose
      of placebo were given to healthy infants at 6, 10, and 14 weeks of age. Subjects
      also received three doses of DTwP-HepB-Hib (diphtheria, tetanus, whole-cell
      pertussis, hepatitis B, and haemophilus influenzae type b conjugate - pentavalent
      vaccine) and oral polio vaccine concomitantly at 6, 10, and 14 weeks of age and a
      single dose of inactivated polio vaccine at 14 weeks of age. Blood samples were
      collected four weeks after the final vaccination to assess immune responses to
      all the vaccines administered. For diphtheria, tetanus, hepatitis B, Hib, polio
      type 1, and polio type 3 antibodies, non-interference was to be supported if the
      lower limit of the two-sided 90% confidence interval (CI) for the seroprotection
      rate difference for the BRV-PV group minus the Rotarix(r) group was >10.0%. For
      pertussis antibodies, non-interference was to be supported if the lower limit of
      the two-sided 90% CI for the ratio of geometric mean concentrations (GMCs) was
      >0.5. RESULTS: A total of 1500 infants were randomized to either BRV-PV (1125
      infants) or Rotarix(r) (375 infants), of which 1341 completed the study as per
      the protocol. More than 97% of subjects achieved seroprotective antibody titres
      against diphtheria, tetanus, hepatitis B, Hib, polio type 1, and polio type 3 in
      both groups. The difference in seroprotection rates between the BRV-PV group and
      the Rotarix(r) group for all these antibodies was less than 1%. The ratio of GMCs
      of anti-pertussis IgG concentrations for the BRV-PV group versus Rotarix(r) was
      1.04 [90% CI: 0.90; 1.19]. CONCLUSION: BRV-PV does not interfere with the
      immunogenicity of concomitantly administered routine infants vaccines.

PMID- 30104116
TI  - Replication-independent reduction in the number and diversity of recombinant
      progeny viruses in chickens vaccinated with an attenuated infectious
      laryngotracheitis vaccine.
AB  - Recombination is closely linked with virus replication and is an important
      mechanism that contributes to genome diversification and evolution in
      alphaherpesviruses. Infectious laryngotracheitis (ILTV; Gallid alphaherpesvirus
      1) is an alphaherpesvirus that causes respiratory disease in poultry. In the
      past, natural (field) recombination events between different strains of ILTV
      generated virulent recombinant viruses that have caused severe disease and
      economic loss in poultry industries. In this study, chickens were vaccinated with
      attenuated ILTV vaccines to examine the effect of vaccination on viral
      recombination and diversity following subsequent co-inoculation with two field
      strains of ILTV. Two of the vaccines (SA2 and A20) prevented ILTV replication in
      the trachea after challenge, but the level of viral replication after co
      infection in birds that received the Serva ILTV vaccine strain did not differ
      from that of the mock-vaccinated (control) birds. Even though the levels of viral
      replication were similar in the two groups, the number of recombinant progeny
      viruses and the level of viral diversity were significantly lower in the Serva
      vaccinated birds than in mock-vaccinated birds. In both the mock-vaccinated and
      Serva-vaccinated groups, a high proportion of recombinant viruses were detected
      in naive in-contact chickens that were housed with the co-inoculated birds. Our
      results indicate that vaccination can limit the number and diversity of
      recombinant progeny viruses in a manner that is independent of the level of virus
      replication. It is possible that immune responses induced by vaccination can
      select for virus genotypes that replicate well under the pressure of the host
      immune response.

PMID- 30104118
TI  - Varicella in the prison setting: A report of three outbreaks in Rhode Island and
      a review of the literature.
AB  - BACKGROUND: The prison setting carries unique risks for varicella outbreaks and
      the disease in adults, particularly those who are immunocompromised, can be life
      threatening. In 2016-17, there were three outbreaks of varicella at three
      different correctional facilities in Rhode Island. The Centers for Disease
      Control and Prevention (CDC) recommend post-exposure vaccination within three to
      five days for affected populations however the Federal Bureau of Prisons (BOP)
      notes the logistical challenges of vaccinating exposed incarcerated individuals.
      MATERIAL AND METHODS: A descriptive analysis was performed for each outbreak
      along with an overview of the response. Varicella serologies were obtained from
      the exposed population at each facility and the results compiled for comparative
      analysis. A literature review was then performed to identify and analyze other
      reported varicella outbreaks in incarcerated populations. RESULTS: In each
      outbreak, the sentinel event was an inmate with herpes zoster. In prison A, there
      were 432 inmates exposed to the virus leading to 5 cases of varicella, while the
      outbreak in Prison B exposed 46 inmates and led to 3 cases. In Prison C, there
      was one case of primary varicella and 97 inmates were exposed. DISCUSSION: It is
      remarkable that there were 3 unrelated outbreaks in a short time and, although
      corroborating data would be necessary to establish a trend, it may signal an
      increased risk of varicella transmission within this population. Correctional
      facilities should remain vigilant and have plans for managing the disease
      including isolation protocols, serology testing and post-exposure vaccination
      when indicated. While the BOP does not provide clear recommendations on the use
      of post-exposure prophylaxis during an outbreak response in this population, the
      experience in Rhode Island and the review of the literate demonstrate steps that
      can be taken to facilitate a response including post-exposure vaccination in line
      with CDC recommendations.

PMID- 30104119
TI  - Immune checkpoint inhibitor therapy-induced hypophysitis ~ a case series of
      Taiwanese patients.
AB  - Immune checkpoint blockade-based immunotherapy is a new modality of cancer
      treatment with a unique mechanism that has gained increased numbers of indication
      and is now used in several cancer types. However, immune-related adverse events
      (irAEs) emerge as a new entity of diseases involving one or multiple organ
      systems. irAEs could result in interruption of immunotherapy, morbidities or even
      death. Among various manifestations of irAEs, immune-mediated hypophysitis is
      rare but important, requiring prompt diagnosis and treatment to avoid life
      threatening conditions. We report seven cases of immune-mediated hypophysitis in
      Taiwan. They suffered from various types of advanced cancer and received
      different regimens of immune checkpoint inhibitors. The time of onset after
      initiation of immunotherapy ranged from 5 to 36 weeks. All seven subjects were
      diagnosed of central adrenal insufficiency, while four of them had primary
      hypothyroidism. There was no typical finding of infiltrative hypophysitis on the
      pituitary MRI. There was no documented hormone recovery after diagnosis of
      hypophysitis, and the tumor responses to immunotherapy were variable in these
      seven patients. In conclusion, immune-mediated hypophysitis is often
      irreversible. Fortunately, it can be managed adequately with hormone
      replacements. Further investigations are warranted to unveil underlying
      mechanisms and ethnic differences to guide the solutions.

PMID- 30104117
TI  - Immunogenicity and safety of measles-mumps-rubella vaccine at two different
      potency levels administered to healthy children aged 12-15 months: A phase III,
      randomized, non-inferiority trial.
AB  - BACKGROUND: The potency of live viral vaccines decreases over time. We compared
      the immunogenicity and safety of GSK measles-mumps-rubella vaccine (MMR-RIT)
      formulations at two different potencies with that of the commercially-available
      MMR II formulation. METHODS: In this phase III observer-blind clinical study
      (NCT01681992), 4516 healthy children aged 12-15 months were randomized (1:1:1
      ratio) to receive one dose of MMR-RIT at the minimum potency used for this study
      (MMR-RIT-Min) or MMR-RIT at the second lowest potency used for this study (MMR
      RIT-Med), or control MMR II vaccine. A second dose (MMR-RIT or MMR II) was
      administered 42 days after the first. The study had 10 co-primary objectives to
      evaluate MMR-RIT versus MMR II immunogenicity via a hierarchical procedure. Anti
      measles and anti-rubella antibodies were measured by ELISA and anti-mumps
      antibodies by ELISA and unenhanced plaque reduction neutralization test (PRNT).
      RESULTS: Each formulation induced immune responses to all vaccine antigens after
      each MMR dose. While the primary objectives for MMR-RIT-Min were not met, MMR-RIT
      Med induced immune responses as measured by ELISA against the three vaccine
      antigens that met pre-specified non-inferiority criteria. The immune response
      following MMR-RIT-Med against mumps measured by PRNT failed the non-inferiority
      criterion for seroresponse rate: the 97.5% confidence interval lower limit (
      10.94%) was beyond the pre-defined limit of -10%. Immune responses were
      comparable among groups post-dose 2. No safety concerns were identified, and MMR
      RIT and MMR II vaccines had similar reactogenicity and safety profiles.
      CONCLUSIONS: One dose of MMR-RIT formulation with lower potency (MMR-RIT-Med)
      induced a non-inferior immune response compared to commercial MMR II vaccine,
      measured by ELISA in one-year-old children. Non-inferiority was not demonstrated
      in terms of immune response against mumps virus measured by unenhanced PRNT,
      although the difference was of uncertain clinical relevance. After the second
      dose, immune responses were comparable among the MMR-RIT and MMR II groups.

PMID- 30104120
TI  - Corrigendum to "Childhood-onset generalized epilepsy in Bainbridge-Ropers
      syndrome" [Epilepsy Res. 140 (2018) 166-170].

PMID- 30104121
TI  - Synthesis, molecular docking, and biological activity of 2-vinyl chromones:
      Toward selective butyrylcholinesterase inhibitors for potential Alzheimer's
      disease therapeutics.
AB  - We investigated the biological activity of a series of substituted chromeno[3,2
      c]pyridines, including compounds previously synthesized by our group and novel
      compounds whose syntheses are reported here. Tandem transformation of their
      tetrahydropyridine ring under the action of activated alkynes yielding 2
      vinylsubstituted chromones was used to prepare nitrogen-containing derivatives of
      a biologically active chromone system. The inhibitory activity of these chromone
      derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and
      carboxylesterase (CaE) was investigated using the methods of enzyme kinetics and
      molecular docking. Antioxidant (antiradical) activity of the compounds was
      assessed in the ABTS assay. The results demonstrated that a subset of the studied
      chromone derivatives selectively inhibit BChE but do not exhibit antiradical
      activity. In addition, the results of molecular docking effectively explained the
      observed features in the efficacy, selectivity, and mechanism of BChE inhibition
      by the chromone derivatives.

PMID- 30104122
TI  - Radiosynthesis and in vivo evaluation of a fluorine-18 labeled pyrazine based
      radioligand for PET imaging of the adenosine A2B receptor.
AB  - On the basis of a pyrazine core structure, three new adenosine A2B receptor
      ligands (7a-c) were synthesized containing a 2-fluoropyridine moiety suitable for
      18F-labeling. Compound 7a was docked into a homology model of the A2B receptor
      based on X-ray structures of the related A2A receptor, and its interactions with
      the adenosine binding site were rationalized. Binding affinity data were
      determined at the four human adenosine receptor subtypes. Despite a rather low
      selectivity regarding the A1 receptor, 7a was radiolabeled as the most suitable
      candidate (Ki(A2B) = 4.24 nM) in order to perform in vivo studies in mice with
      the aim to estimate fundamental pharmacokinetic characteristics of the compound
      class. Organ distribution studies and a single PET study demonstrated brain
      uptake of [18F]7a with a standardized uptake value (SUV) of ~1 at 5 min post
      injection followed by a fast wash out. Metabolism studies of [18F]7a in mice
      revealed the formation of a blood-brain barrier penetrable radiometabolite, which
      could be structurally identified. The results of this study provide an important
      basis for the design of new derivatives with improved binding properties and
      metabolic stability in vivo.

PMID- 30104123
TI  - Continuous glucose monitoring in youth with cystic fibrosis treated with
      lumacaftor-ivacaftor.
AB  - BACKGROUND: The effects of lumacaftor-ivacaftor therapy on glycemia have not been
      thoroughly investigated. Continuous glucose monitoring (CGM) provides detailed
      information about glycemic patterns and detects glucose abnormalities earlier
      than traditional screening tools for diabetes. METHODS: CGM measures, HbA1c, and
      oral glucose tolerance test (OGTT) results were collected and within-subject
      results compared in F508del homozygous youth with CF before and after initiation
      of lumacaftor-ivacaftor using the Wilcoxon signed-rank test. RESULTS: Nine youth
      with CF (6 males, median age 12.7 years) were enrolled. CGM was performed in all
      participants before (median 26 weeks) and after lumacaftor-ivacaftor (median 29
      weeks). HbA1c and fasting plasma glucose increased (p = .02) after lumacaftor
      ivacaftor initiation. No changes in OGTT 1 h or 2 h glucose nor CGM measures were
      observed overall. When analyzed by sex, males showed lower glycemic variability,
      as reflected by the mean amplitude of glycemic excursions, on the post-treatment
      CGM. CONCLUSIONS: Glycemic abnormalities persisted in CF patients treated with
      lumacaftor-ivacaftor, although sex-dependent differences in glycemic response to
      treatment may exist.

PMID- 30104124
TI  - Wild birds as host of Borrelia burgdorferi sensu lato in northwestern Argentina.
AB  - Borrelia burgdorferi sensu lato (s. l.) spirochetes are associated with a wide
      range of vectors and hosts. Birds are important hosts in the ecology of some hard
      ticks (Ixodidae) in northwestern Argentina, where B. burgdorferi s.l. have been
      detected in Ixodes pararicinus. We evaluated Borrelia infection in ticks
      collected from wild birds by molecular analysis through the presence of Borrelia
      DNA (by nested-PCR targeting the fla gene). A total of 381 ticks (357 larvae and
      24 nymphs) belonging to four species (I. pararicinus, Haemaphysalis juxtakochi,
      Haemaphysalis leporispalustris and Amblyomma sp.) were collected. Partial
      sequences of the fla gene of Borrelia (100% identical to Borrelia sp. haplotype I
      from Argentina) were detected in 9 of 70 tick pools (6 pools of larvae and 1 pool
      of nymphs of I. pararicinus, and in 2 pools of H. juxtakochi larvae) collected on
      Turdus rufiventris, Syndactila rufosuperciliata and Troglodytes aedon. The
      results of this study suggest that resident birds have reservoir capacity for
      Borrelia sp. haplotype I.

PMID- 30104125
TI  - A Longitudinal Study Investigating Synchronization in a Singing Quintet.
AB  - Research suggests that synchronization between musicians during ensemble
      performances can be affected by the rhythmic or tonal complexity of the piece
      being performed and by group roles such as leader-follower relationships. Since
      previous studies have mostly been conducted within single performance sessions,
      developmental aspects of interpersonal synchronization in ensembles remain
      underinvestigated. This longitudinal study followed a newly formed singing
      ensemble from initial rehearsals to the performance stage in order to investigate
      the evolution of synchronization between advanced singing students during a
      university term of study in relation to the musical content of the piece and
      leader-follower relationships. An advanced postgraduate singing quintet was
      recorded using head-worn microphones and laryngograph electrodes to allow
      fundamental frequency evaluation of the individual voices. The quintet, formed to
      complete a 1-year Master's programme in ensemble singing, rehearsed two pieces
      composed for the study, during five rehearsals over 3 months. Singers practised
      the same pieces in a randomized order across rehearsals and performed three
      repetitions of the same pieces before and after each rehearsal, resulting in six
      recordings per piece/rehearsal. Audio and laryngograph data of the repeated
      performances were collected, and synchronization was measured by extracting note
      times from the fundamental frequency values. The asynchronies of the two pieces
      before and after rehearsals were calculated and compared both within rehearsals
      (pre and post) and between rehearsals (rehearsals 1-5). Results demonstrate an
      increase in the precision of synchronization over the course of study, depending
      on the piece being rehearsed, and a more variable synchronization for the more
      rhythmically complex piece. Results also show changes in the distribution of the
      tendency to precede all co-performers across rehearsals, which became equally
      distributed among the musicians during the last rehearsal. The results reported
      here could have important implications for the tailoring of rehearsal strategies
      that could improve interpersonal synchronization between musicians during
      ensemble performances.

PMID- 30104126
TI  - Voice Disorders and Voice Knowledge in Choir Singers.
AB  - OBJECTIVES: Singers have reported higher prevalence of vocally harmful behaviors,
      vocal symptoms, and voice disorders than nonsingers have. The purpose of this
      study was to investigate the prevalence of voice disorders among choir singers
      and to discover the risk factors associated with voice disorders. Another purpose
      was to explore the choir singers' knowledge about the anatomy and physiology of
      the voice, and voice ergonomics. METHODS: Three hundred and fifteen adult choir
      singers, 65% women, and 35% men, completed a web-questionnaire. The questionnaire
      included demographic questions and questions about vocal symptoms, risk factors
      for voice disorders, and voice knowledge. RESULTS: Twenty one percent of the
      participants experienced two or more frequently occurring vocal symptoms, which
      was defined as having a functional voice disorder. Choir singers with a vocally
      demanding profession were almost twice as likely to report several frequently
      occurring vocal symptoms. Health-related risk factors, such as inhalant allergy
      and asthma, had a significant relation with the number of vocal symptoms. The
      overall voice knowledge among the choir singers seemed limited. CONCLUSIONS: The
      prevalence of voice disorders among choir singers seems to be similar to the
      prevalence rate among professional voice users. Choir singers with a vocally
      demanding profession are at a higher risk of developing a functional voice
      disorder. The results of this study raise the importance of educating choir
      singers about the voice, in order to prevent development of voice disorders.

PMID- 30104127
TI  - Effects of Voice Therapy Using the Lip Trill Technique in Patients With Glottal
      Gap.
AB  - OBJECTIVES: Lip trills are widely used as a voice warm-up technique among
      singers. However, little is known about the effects of lip trills in cases of
      voice disorders. We examined the therapeutic effects of lip trills in patients
      with glottal gap. METHODS: Patients with glottal gap were classified into three
      groups according to the type of gap: gap-only, gap with muscle tension dysphonia
      (MTD), and a sulcus vocalis group. Patients underwent perceptual,
      acoustic/aerodynamic analyses, stroboscopic evaluations, and subjective analyses
      using a questionnaire before and after lip trills. The results were analyzed
      before and after trills and according to and between the groups. RESULTS: The
      results in 42 patients were analyzed. Most of the parameters were improved and
      glottal gap was significantly reduced after trills in all patients. In the gap
      only group (n = 19), most of the parameters showed improvement and were within
      the respective normal ranges, and glottal gap was improved after trills. In the
      MTD group (n = 13), although many parameters were improved, the improvement was
      not as prominent as in the gap-only group. In the sulcus vocalis group (n = 10),
      only some of the parameters were improved and the improvement in glottal gap was
      limited. CONCLUSIONS: Lip trills were an effective treatment for glottal gap. The
      therapeutic effect was prominent in the gap-only group, followed by the MTD and
      sulcus vocalis groups. Trills can be used as an adjuvant treatment option in
      voice therapy in cases of various voice disorders.

PMID- 30104128
TI  - Implementation of the Asthma Control Test in Primary Care to Improve Patient
      Outcomes.
AB  - BACKGROUND: Asthma is one of the major chronic diseases in the pediatric
      population, affecting 9.5% of children. The National Heart, Lung, and Blood
      Institute recommends the use of the Asthma Control Test (ACT) for periodic
      assessment of asthma control. The purpose of this evidence-based project was to
      implement the Asthma Control Test screening tool into the primary care practice
      to improve management of patients with asthma by more accurately addressing
      asthma control. METHODS: The project was a pre- and post-implementation study
      comparing two different groups of patients with asthma seen at the clinic over 5
      week periods. RESULTS: After the implementation of the educational program and
      project, 82.6% of advanced practice registered nurses and 30.7% of pediatric
      resident physicians used an Asthma Control Test, resulting in identification of 9
      (21%) patients who were considered not well-controlled. All (100%) of those
      children identified as not well-controlled through the Asthma Control Test
      received an adjustment in their medication therapy. CONCLUSIONS: The Childhood
      ACT and ACT are simple, self-administered, validated questionnaires that can
      easily be incorporated into a primary care practice to assess the level of asthma
      control and to identify patients with asthma that is not well controlled.

PMID- 30104129
TI  - President's Message: A Year in Review.

PMID- 30104130
TI  - Single embryo transfer for all.
AB  - There is a global recognition of the need to reduce multiple pregnancies
      following assisted reproductive technology. Complications of multiple pregnancies
      can be simply avoided by replacing one embryo at a time. Most policies to reduce
      the number of double or higher order embryo transfers involve predicting which
      patients are at most risk by using a multiple birth minimisation strategy. These
      frequently consider factors such as patient age, previous treatments and embryo
      quality. However, with improvements in methods of embryo culture, embryo
      selection and cryopreservation, this chapter will question whether, at present,
      it is time to move to single embryo transfer (SET) for all.

PMID- 30104131
TI  - The surgical management of extra-articular ankylosis in noma patients.
AB  - Extraarticular ankylosis occurs frequently in children suffering from noma
      sequelae. Over 20years of operating on these patients, we observed high
      recurrence of mouth opening limitation. We therefore progressively changed our
      surgical strategy. This retrospective study compares the impact of different
      parameters (types of surgery, noma type, physiotherapy compliance, age and sex)
      on immediate and long-term mouth opening. It includes a series of 121 patients
      with extraarticular ankylosis operated on between 1990 and 2015. Soft tissue
      reconstruction evolved from local and pedicled flaps to large free flaps. Mouth
      opening was performed by bone-bridge excision, sometimes associated to
      contralateral coronoidectomy. Mouth opening technique including bilateral
      coronoidectomy with free flap reconstruction was the only independent factor for
      significantly better immediate mouth opening with a mean increase of 8.7mm [95%
      confidence interval (CI) 4.3-13.1, P<0.001) and this effect was maintained in the
      3years of follow-up. Another positive factor related to long-term results was
      excellent physiotherapy, while noma type 4 was a negative factor. Recurrence
      remains problematic in the management of noma sequelae. If physiotherapy and long
      term follow-up cannot be offered, patients should not be operated on, because if
      limitation of mouth opening recurs, oral feeding may become impossible when a
      facial defect has been reconstructed.

PMID- 30104133
TI  - Considerations for the need of recommendations for the research and publication
      of DNA methylation results.

PMID- 30104132
TI  - A view of maternal mortalities in women conceiving through assisted reproductive
      techniques: A nation-based study of Turkey.
AB  - BACKGROUND: Our aim was to evaluate maternal mortality causes among Turkish women
      giving birth after assisted reproductive techniques (ARTs). METHODS: All maternal
      deaths following conception with ART pregnancies were identified through the
      National Maternal Mortality Surveillance System. We analyzed the system data
      collected between 2007 and 2014. During this period, there were 10,369,064 live
      births and 1788 maternal deaths resulting from both direct and indirect causes.
      We identified 28 maternal death cases following ART procedures. The age,
      gestational age at birth, number of antenatal visits, delivery route, time of
      death, cause of death, and neonatal outcomes were recorded. Also, any existing
      delay (phase 1, 2, or 3) and preventability of maternal death were assessed.
      RESULTS: Hypertensive disorders, pulmonary embolism, and cardiovascular disease
      were the leading causes of maternal death. Twelve (40%) women were over 35 years
      of age. Of the deaths, 15 (54%) were attributed to indirect causes. The number of
      unpreventable maternal deaths was 19 (67.9%), and 9 (36%) were classified as
      preventable after being assessed by the review commission of maternal mortality.
      CONCLUSION: Pregnancies conceived with ARTs should undergo a careful assessment
      of risk factors for hypertensive disorders, pulmonary embolism and cardiovascular
      diseases. Those women require closer antenatal surveillance because 1/3 of these
      deaths were preventable.

PMID- 30104134
TI  - Onychomycosis due to Achaetomium strumarium.
AB  - Onychomycosis is the most common infection of the toe-nails or finger-nails and
      it may be caused by a large variety of fungal species. Achaetomium species which
      belong to the phylum Ascomycota (Family Chaetomiaceae), are usually soil
      saprophytes or endophytic fungi which have been rarely reported as human or
      animal pathogens. Here, we report a case of onychomycosis caused by Achaetomium
      strumarium in a healthy person who showed involvement of all fingers of both
      hands with yellowish brown discoloration. The causative agent isolated was
      identified as Achaetomium species by morphology, colony morphometry and growth at
      high temperature and as A. strumarium from DNA sequence of ITS region.
      Onychomycosis from this case responded satisfactorily with per os (P. O.; oral)
      and topical application of Terbinafine.

PMID- 30104135
TI  - Promising synergistic activity of fluconazole with bioactive Guttiferone-A and
      derivatives against non-albicans Candida species.
AB  - Natural products with diverse bioactivities and structures are an important
      source of novel chemicals with pharmaceutical potentials. Combinations of
      bioactive compounds with classical antimicrobial agents against drug-resistant or
      low-susceptible Candida spp. have been studied. Guttiferone-A and its derivatives
      were combined with fluconazole through the checkerboard method and tested against
      Candida spp. The results obtained, especially the Fractional Inhibitory
      Concentration Index (FICI) determined to the combinations, suggests promising
      results on the treatment of Candida infections, principally for species that
      present resistance or low antifungal susceptibility. The best result was seen for
      C. krusei, in which a synergic action of the association between fluconazole and
      Guttiferone-A resulted in a reduction of more than 100-fold in the alone
      inhibitory concentration (MIC) of fluconazole. Synergism was also noted in the
      association of fluconazole with the synthetic derivatives LFQM-79, LFQM-80 and
      LFQM-81 against C. glabrata, with reduction of up to four times in the alone IC
      of fluconazole. These results suggest the possibility of combined administration
      with reduction of doses and side effects of drugs conventionally used against
      Candida spp. and the promising therapeutic action of Guttiferone-A.

PMID- 30104136
TI  - Emerging Strategies for Genome Editing in the Brain.
AB  - Despite the unparalleled therapeutic promise of genome editing, its curative
      power is currently limited by the substantial difficulty in delivering DNA
      cutting enzymes to the cells in need of correction. A recent study demonstrates
      the potential for the delivery of pre-assembled genome-editing enzymes in the
      form of ribonucleoprotein complexes, which were used to rescue a mouse model of
      fragile X syndrome (FXS).

PMID- 30104137
TI  - Ecological Stoichiometry for Parasitologists.
AB  - Ecological stoichiometry (ES) is an ecological theory used to study the
      imbalances of chemical elements, ratios, and flux rates among organisms and the
      environment to better understand nutrient cycling, energy flow, and the role of
      organisms in ecosystems. Parasitologists can use this framework to study
      phenomena across biological scales from genomes to ecosystems. By using the
      common currency of elemental ratios such as carbon:nitrogen:phosphorus,
      parasitologists are beginning to explicitly link parasite-host interactions to
      ecosystem dynamics. Thus, ecological stoichiometry provides a framework for
      studying the feedbacks of parasites on the environment as well as the effects of
      the environment on parasites and disease.

PMID- 30104138
TI  - The FTO rs9939609 polymorphism and obesity risk in teens: Evidence-based meta
      analysis.
AB  - OBJECTIVE: This meta-analysis aims evaluate the association of the polymorphism
      rs9939609 of FTO with the risk of obesity among children and adolescents, based
      on the assessment of four genetic models: codominant, dominant, recessive alleles
      model. METHODS: Case-control studies, published between the years 2011-2015, were
      selected from tree available databases (PubMed, Scopus and Web of Science) and
      were analysed using Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) recommendations. Thirteen studies were included totalling
      15,613 participants, divided into 7311 cases and 8302 controls. RESULTS: The FTO
      rs9939609 polymorphism was significantly associated with increased risk of
      obesity in children and adolescents for homozygous genotypes AA and heterozygous
      AT (TT vs. AT+AA: OR=0.723, 95% CI 0.629 to 0.832; p<0.0001). CONCLUSION: This
      meta-analysis shows that the FTO rs9939609 polymorphism in the gene is a risk
      factor for obesity in children and adolescents with the presence of the A allele,
      both homozygous genotype AA situation, as heterozygous AT.

PMID- 30104139
TI  - Integration despite Fractionation: Continuous Flash Suppression.

PMID- 30104140
TI  - Using Anesthesia to Reveal the Elements of Consciousness.
AB  - General anesthesia provides an invaluable experimental tool to probe the
      essential neural circuits that underlie consciousness. A new study reports that
      cholinergic stimulation of the prefrontal cortex restores wake-like behaviors in
      anesthetized rodents, suggesting that cholinergic inputs to the prefrontal cortex
      play a fundamental role in modulating consciousness.

PMID- 30104141
TI  - Inferiorly based lotus petal flap & laser therapy in difficult pilonidal sinus
      management.
AB  - AIM: To assess the efficacy of the lotus petal flap in difficult pilonidal sinus
      management. BACKGROUND: Pilonidal sinuses may be difficult to treat. Five year
      recurrence rates range from 18% to 50% Recurrence rates fall with primary closure
      rather than healing by secondary intention. Techniques such as z-plasty however,
      distort natal architecture. The lotus petal flap taken from the superior buttock
      fills dead space whilst conforming to the natural concave appearance of the natal
      cleft. The contralateral buttock is spared. It is straightforward and
      reproducible. Multiple perforators make it robust and promote wound healing in
      this difficult group. METHOD: We present a series of 14 patients who had a lotus
      petal flap reconstruction following pilonidal sinus excision between 2007 and
      2015. The majority of these patients had previous multiple failed attempts at
      eradication. Recurrence rates, re-operation rates, time for complete healing,
      wound breakdown, discharge, infection, cosmesis and patient comfort were
      assessed. RESULTS: Many patients had coarse hair; felt to predispose to
      recurrence of symptoms, poor hygiene and prolonged wound healing. 50% of patients
      underwent Alexandrite laser (755 nm wavelength) for a minimum of 6 treatments.
      There was excellent compliance and good patient outcome. Overall in this complex
      patient group only 14% had prolonged wound healing and recurrence rates were
      lower than those in the literature. CONCLUSION: The lotus petal flap is an
      excellent choice for problematic pilonidal sinus reconstruction. When combined
      with tumour like excision, meticulous surgical technique and complimentary laser
      hair removal results can be improved further.

PMID- 30104142
TI  - How to assess the volume of a DIEP flap using a free online calculator: The DIEP
      V (volume) method.
AB  - INTRODUCTION: Among the few methods available, none is able to determine
      accurately the volume of a DIEP flap. Specimen weight is commonly used to assess
      the amount of flap needed to reconstruct a breast, but the density of breast is
      different from that of abdominal tissues; therefore, the volume should be used as
      a unique unit of measure. The purpose of this study was to provide a simple
      method to calculate the predicted volume of a DIEP flap in order to match the
      volume of the breast being reconstructed. MATERIAL AND METHOD: We hypothesised
      that the shape best resembling a DIEP flap was a truncated pyramid. Based on this
      shape, we tailored 30 DIEP flap models using the discarded tissue after
      unilateral DIEP flap breast reconstructions. The awaited volume (AV) of the
      models was calculated with a free online calculator measuring the length and
      height with a ruler, and width (fat thickness) with Ultrasound (US). The real
      volume (RV) of the models was calculated using water displacement method. AV and
      RV were compared and statistical analysis was performed. RESULTS: The mean
      difference between the AV and the RV was not statistically significant with a
      mean estimation error of 6.75%. When the AVs were plotted against the RVs, the
      two data sets were highly statistically correlated (correlation coefficient (r =
      0.997). CONCLUSIONS: The proposed tool can be a useful, precise, easy and
      accessible tool to improve the current DIEP flap size assessment improving
      outcomes for both surgeons and patients.

PMID- 30104143
TI  - Fetal pericallosal lipomas - Clues to diagnosis in the second trimester.
AB  - INTRODUCTION: Pericallosal lipomas (PCL) are congenital soft masses of adipose
      cells encapsulated by a thin layer of fibrous tissue, appearing adjacent to the
      corpus callosum (CC). The lipomas are usually diagnosed prenatally during the
      third trimester. The purpose of this study was to identify 2nd trimester
      ultrasound findings that may hint to a later diagnosis of PCL and to evaluate
      their MRI evolution. METHODS: A multicenter study of fetuses diagnosed during the
      3rd trimester with a PCL in 7 fetal ultrasound units between 2001 and 2017. We
      reevaluated the ultrasound and MRI images starting from the referral examination
      and until the time of diagnosis, searching for clues that could have prompted an
      earlier diagnosis. Parents were contacted at the end of the study period to
      obtain information regarding development and neurological examination. RESULTS:
      Fifteen patients with PCL were diagnosed during the study period; fourteen had
      second trimester scans. A 2nd trimester diagnosis was established in only 2
      (13.3%). Anomalies of the CC were evident in 8/14 patients during the 2nd
      trimester scan and included: short length (n = 4), increased thickness (n = 1),
      complete agenesis (n = 2) and partial agenesis (n = 1). Third trimester
      ultrasound scans were considered diagnostic of PCL in all 12 remaining cases, in
      eight it was considered an isolated finding. Postnatal neurological evaluation in
      the isolated cases revealed normal development in all children. One child was
      diagnosed with attention deficit disorder. CONCLUSIONS: Non visualization of a
      PCL during the 2nd trimester is common, and should not be considered a diagnostic
      error. An underlying PCL should be included in the differential diagnosis of CC
      anomalies during this time period, necessitating further follow up into the 3rd
      trimester.

PMID- 30104144
TI  - The role of physiological arousal for self-reported emotional empathy.
AB  - The capacity to represent the emotional and mental states of others is referred
      to by the concept of empathy. Empathy further differentiates into an emotional
      and a cognitive subcomponent, which in turn is known to require a tacit
      perspective-taking process. However, whether the empathizer by himself needs to
      enter an affective state as a necessary precondition for emotional empathy
      remains a matter of debate. If empathy would require a vicarious emotional
      reaction, specific physiological markers of affective responding should be
      detectable in the empathizing person. In the present study, we investigated the
      relationship between self-reported empathy and psychophysiological responses in
      young, healthy participants. We assessed emotional and cognitive empathy with the
      Multifaceted Empathy Test on the one hand and the corresponding heart rate and
      skin conductance responses (SCR), affective startle modulation and heart rate
      variability on the other. We found a negative relationship between SCR and self
      reported emotional empathy: higher SCR to emotional stimuli predicted lower
      empathy ratings. We conclude that physiological arousal is not necessary and
      might even diminish empathy for others.

PMID- 30104145
TI  - Recurrent jejunal metastasis from occult lung cancer.

PMID- 30104146
TI  - One-stage direct-to-implant breast reconstruction using acellular dermal matrix.

PMID- 30104147
TI  - Quality of life and patient satisfaction after one-stage implant-based breast
      reconstruction with an acellular dermal matrix versus two-stage breast
      reconstruction (BRIOS): primary outcome of a randomised, controlled trial.
AB  - BACKGROUND: There is increasing interest in the use of acellular dermal matrices
      (ADMs) in implant-based breast reconstruction (IBBR). Suggested advantages are
      that ADMs facilitate one-stage IBBR and improve aesthetic outcomes. We compared
      immediate one-stage ADM-assisted IBBR with two-stage IBBR (current standard of
      care). Our previously reported secondary endpoint showed that one-stage ADM
      assisted IBBR was associated with significantly more adverse outcomes. Here, we
      present the primary endpoint results aiming to assess whether one-stage IBBR with
      ADM provides higher patient-reported quality of life (QOL) compared with two
      stage IBBR. METHODS: This multicentre, open-label, randomised controlled trial
      (BRIOS study) was done in eight hospitals in the Netherlands. We recruited women
      aged older than 18 years with breast carcinoma or a genetic predisposition who
      intended to undergo skin-sparing mastectomy and immediate IBBR. Participants were
      randomly assigned to undergo one-stage IBBR with ADM (Strattice, LifeCell,
      Branchburg, NJ, USA) or two-stage IBBR. Randomisation was stratified by centre
      and indication for surgery (oncological or prophylactic) in blocks of ten
      participants. The primary endpoint was patient-reported QOL, as measured with the
      BREAST-Q (ie, health-related QOL scales and satisfaction scales), in the modified
      intention-to-treat population. The study follow-up is complete. This study is
      registered with the Netherlands Trial Register, number NTR5446. FINDINGS: Between
      April 14, 2013, and May 29, 2015, we enrolled 142 women, of whom 69 were randomly
      assigned to receive one-stage ADM-assisted IBBR and 73 to receive two-stage IBBR.
      After exclusions, the modified intention-to-treat population comprised 60
      patients in the one-stage group and 61 patients in the two-stage group. Of these,
      48 women (mean follow-up 17.0 months [SD 7.8]) in the one-stage group and 44
      women (17.2 months [SD 6.7]) in the two-stage group completed the BREAST-Q at
      least 1 year after implant placement. We found no significant differences in
      postoperative patient-reported QOL domains, including physical wellbeing (one
      stage mean 78.0 [SD 14.1] vs two-stage 79.3 [12.2], p=0.60), psychosocial
      wellbeing (72.6 [17.3] vs 72.8 [19.6], p=0.95), and sexual wellbeing (58.0 [17.0]
      vs 57.1 [19.5], p=0.82), or in the patient-reported satisfaction domains:
      satisfaction with breasts (63.4 [15.8] vs 60.3 [15.4], p=0.35) and satisfaction
      with outcome (72.8 [19.1] vs 67.8 [16.3], p=0.19). INTERPRETATION: Taken together
      with our previously published findings, one-stage IBBR with ADM does not yield
      superior results in terms of patient-reported QOL compared with two-stage IBBR.
      Risks for adverse outcomes were significantly higher in the one-stage ADM group.
      Use of ADM for one-stage IBBM should be considered on a case-by-case basis.
      FUNDING: Pink Ribbon, Nuts-Ohra, and LifeCell.

PMID- 30104148
TI  - Deep Learning for Plant Stress Phenotyping: Trends and Future Perspectives.
AB  - Deep learning (DL), a subset of machine learning approaches, has emerged as a
      versatile tool to assimilate large amounts of heterogeneous data and provide
      reliable predictions of complex and uncertain phenomena. These tools are
      increasingly being used by the plant science community to make sense of the large
      datasets now regularly collected via high-throughput phenotyping and genotyping.
      We review recent work where DL principles have been utilized for digital image
      based plant stress phenotyping. We provide a comparative assessment of DL tools
      against other existing techniques, with respect to decision accuracy, data size
      requirement, and applicability in various scenarios. Finally, we outline several
      avenues of research leveraging current and future DL tools in plant science.

PMID- 30104149
TI  - Corrigendum to molecular genetics and emerging therapies for retinitis
      pigmentosa: Basic research and clinical perspective progress in retinal and eye
      research (2018) Vol 63,107-131.

PMID- 30104150
TI  - [Image-guided radiotherapy in lung cancer].
AB  - Image-guided radiotherapy takes place at every step of the treatment in lung
      cancer, from treatment planning, with fusion imaging, to daily in-room
      repositioning. Managing tumoral and surrounding thoracic structures motion has
      been allowed since the routine use of 4D computed tomography (4DCT). The
      integration of respiratory motion has been made with "passive" techniques based
      on reconstruction images from 4DCT planning, or "active" techniques adapted to
      the patient's breathing. Daily repositioning is based on regular images, weekly
      or daily, low (kV) or high (MV) energy. MRI and functional imaging also play an
      important part in lung cancer radiation and open the way for adaptative
      radiotherapy.

PMID- 30104151
TI  - Dry skin manifestations in Sjogren syndrome and atopic dermatitis related to
      aberrant sudomotor function in inflammatory allergic skin diseases.
AB  - We have reported characteristic cutaneous manifestations of Sjogren syndrome (SS)
      with special references to autoimmune anhidrosis or hypoidrosis and related
      mucocutaenous manifestations in addition to annular erythema or cutaneous
      vasculitis. Although significance of cutaneous manifestations of SS has been
      gradually recognized in rheumatologists, sudomotor function has not been fully
      evaluated and recognized in the diagnosis of SS except for dermatologists. SS is
      a relatively underestimated collagen disease in contrast to SLE, systemic
      sclerosis, or dermatomyositis, special care should be needed not to make
      misdiagnosis of SS when we see the patients with common skin disease such as,
      drug eruption, infections skin disease or xerosis in the daily practice. In
      contrast to pathomechanisms of dry skin observed in SS, we recently reported that
      reduced sweating function and dry skin seen in atopic dermatitis (AD) are
      mediated by histamine or substance P, those are usually restored to normal levels
      after improvement of the dermatitis by topical corticosteroid ointment with or
      without oral anti-histamine. Therefore, xerotic skin lesions seen in SS and AD
      might be attributable to different pathomechanisms with similar dry skin
      manifestations. We recently reported that SS promotes dry skin when complicated
      with AD possibly due to acceleration of hypoidrosis. In this review, we would
      like to summarize our recent understanding of regulatory mechanism of impaired
      sweating function in allergic inflammatory skin diseases by introducing clinical
      presentations of AD/SS overlap cases as the model of hypoidrotic inflammatory
      skin diseases.

PMID- 30104152
TI  - Geographic and demographic variations of inhalant allergen sensitization in
      Koreans and non-Koreans.
AB  - BACKGROUND: To diagnose and treat respiratory allergic diseases, it is important
      to identify the specific allergens involved. Many differences exist between
      common inhalant allergens depending on the residential environment and
      demographic factors. This study aimed to compare common inhalant allergens
      between Koreans and non-Koreans according to their residential region, age, and
      sex. METHODS: This study evaluated 15,334 individuals who underwent serum tests
      for multiple allergen-specific immunoglobulin E at a tertiary academic medical
      center between January 2010 and December 2016. The individuals included 14,786
      Koreans and 548 non-Koreans. The AdvanSureTM Allostation assay (LG Life Science,
      Korea) was used to test for 33 inhalant allergens. RESULTS: The house dust mite
      (HDM) was the most common allergen in both Koreans and non-Koreans, although the
      proportion of individuals with HDM sensitization was greater among Koreans. High
      sensitization rates for various pollen types were detected among Koreans in
      Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju
      region. Grass pollen and animal dander were relatively common among individuals
      from the Americas, whereas weed and grass pollen accounted for the 10 most common
      allergens for individuals from Central Asia. The total sensitization rate,
      sensitization to HDM, and sensitization to animal dander peaked among adolescents
      and young adults, then subsequently decreased with age. CONCLUSIONS: This large
      scale study demonstrates that various regional and age-related differences exist
      in the allergen sensitization rates of Koreans and non-Koreans. These data could
      be useful for development of avoidance measures, immunotherapy for causative
      allergens, and policymaking regarding allergic diseases.

PMID- 30104153
TI  - Innate lymphoid cells in organ fibrosis.
AB  - Innate lymphoid cells (ILCs) are a recently identified family of lymphoid
      effector cells. ILCs are mainly clustered into 3 groups based on their unique
      cytokine profiles and transcription factors typically attributed to the subsets
      of T helper cells. ILCs have a critical role in the mucosal immune response
      through promptly responding to pathogens and producing large amount of effector
      cytokines of type 1, 2, or 3 responses. In addition to the role of early immune
      responses against infections, ILCs, particularly group 2 ILCs (ILC2), have
      recently gained attention for modulating remodeling and fibrosis especially in
      the mucosal tissues. Herein, we overview the current knowledge in this area,
      highlighting roles of ILCs on fibrosis in the mucosal tissues, especially
      focusing on the gut and lung. We also discuss some new directions for future
      research by extrapolating from knowledge derived from studies on Th cells.

PMID- 30104155
TI  - The efficacy and toxicity of immune checkpoint inhibitors in a real-world older
      patient population.
AB  - IMPORTANCE: Immunotherapy has emerged as an effective treatment option for the
      management of advanced cancers. The effects of these immune checkpoint inhibitors
      in the older patient population has not been adequately assessed. OBJECTIVE: To
      understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune
      related adverse events (irAE) in the context of real-world management of advanced
      solid cancers. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study
      involved all non-study patients with histologically-confirmed metastatic or
      inoperable solid cancers receiving immunotherapy at Kingston Health Sciences
      Centre. We defined 'older patient' as age >= 75. All statistical analyses were
      conducted under SPSS IBM for Windows version 24.0. MAIN OUTCOMES AND MEASURES:
      Study outcomes included immunotherapy treatment response, survival, as well as
      number, type, and severity of irAEs. RESULTS: Our study (N = 78) had 29 (37%)
      patients age <65, 26 (33%) patients age 65-74, and 23 (30%) patients age >=75.
      Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%,
      22%, and 8% of the study population, respectively. Distributions of ipilimumab
      (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The
      response rates were 28%, 27%, and 39% in the age <65, age 64-74, age >=75 groups,
      respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28
      months (12.28-43.9, 95% CI) and 17 months (0-36.9, 95% CI) in the age <65 and age
      64-74 groups, respectively; the estimated survival probability did not reach 50%
      in the age >=75 group (P = 0.319). There were no statistically significant
      differences found in terms of irAEs, multiple irAEs, severity of grade 3 or
      higher, types of irAEs, and irAEs resolution status when comparing between
      different age groups. CONCLUSION AND RELEVANCE: Our results suggest that patients
      age >=75 are able to gain as much benefit from immunotherapy as younger patients,
      without excess toxicity. Our findings suggest that single agent immunotherapy is
      generally well-tolerated across different age groups with no significant
      difference in the type, frequency or severity of irAEs. Future studies evaluating
      aging and combination immunotherapy are warranted.

PMID- 30104154
TI  - Development of a simple score based on HBeAg and ALT for selecting patients for
      HBV treatment in Africa.
AB  - BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, it is
      essential to scale up antiviral treatment through decentralized services.
      However, access to the conventional tools to assess treatment eligibility (liver
      biopsy/Fibroscan(r)/HBV DNA) is limited and not affordable in resource-limited
      countries. We developed and validated a simple score to easily identify patients
      in need of HBV treatment in Africa. METHODS: As a reference, we used treatment
      eligibility determined by the European Association for the Study of the Liver
      based on alanine aminotransferase (ALT), liver histology and/or Fibroscan and HBV
      DNA. We derived a score indicating treatment eligibility by a stepwise logistic
      regression using a cohort of chronic HBV infection in The Gambia (n = 804). We
      subsequently validated the score in an external cohort of HBV-infected Africans
      from Senegal, Burkina Faso, and Europe (n = 327). RESULTS: Out of several
      parameters, two remained in the final model, namely HBV e antigen (HBeAg) and ALT
      level, constituting a simple score (treatment eligibility in Africa for the
      hepatitis B virus: TREAT-B). The score demonstrated a high area under the
      receiver operating characteristic curve (0.85, 95% CI 0.79-0.91) in the
      validation set. The score of 2 and above (HBeAg-positive and ALT >=20 U/L or
      HBeAg-negative and ALT >=40 U/L) had a sensitivity and specificity for treatment
      eligibility of 85% and 77%, respectively. The sensitivity and specificity of the
      World Health Organization criteria based on the aspartate aminotransferase-to
      platelet ratio index (APRI) and ALT were 90% and 40%, respectively. CONCLUSIONS:
      A simple score based on HBeAg and ALT had a high diagnostic accuracy for the
      selection of patients for HBV treatment. This score could be useful in African
      settings. LAY SUMMARY: Limited access to the diagnostic tools used to assess
      treatment eligibility (liver biopsy/Fibroscan/hepatitis B virus DNA) has been an
      obstacle to the scale up of hepatitis B treatment programs in low- and middle
      income countries. Using the data from African patients with chronic HBV
      infection, we developed and validated a new simple diagnostic score for treatment
      eligibility, which only consists of hepatitis B virus e antigen and alanine
      aminotransferase level. The diagnostic accuracy of the score for selecting
      patients for HBV treatment was high and could be useful in African settings.

PMID- 30104156
TI  - The use of chemotherapy in older patients with stage II and III colon cancer:
      Variation by age and era of diagnosis.
AB  - OBJECTIVE: We aim to examine the use and outcomes of adjuvant chemotherapy in
      older patients with stage II and III colon cancer. MATERIAL AND METHODS: Using
      data from the SEER-Medicare database, we analyzed patients aged 66 or greater,
      diagnosed with stage II or III colon cancer between 1991 and 2007 who received
      surgery. Using Medicare claims, receipt of adjuvant chemotherapy was identified,
      and compared between age bands. Logistic regression modeling was performed to
      assess predictors of receipt of adjuvant chemotherapy, and Cox proportional
      hazards modeling was performed to assess predictors of mortality. RESULTS: A
      total of 31,990 patients were identified: 4371 aged 66-69, 6922 (70-74), 7673 (75
      79), 6807 (80-84), 4266 (85-89), and 1951 (90+). The percent starting adjuvant
      chemotherapy decreased by age cohort: 57% in the 66-69 age cohort, 48% (70-74),
      37% (75-79), 20% (80-84), 8% (85-89), and 1% (90+). Multivariable analysis showed
      that stage III disease was the strongest positive predictor of chemotherapy
      receipt. Multivariable analysis for mortality risk showed that adjuvant
      chemotherapy was associated with an increased risk of mortality in stage II
      patients. Adjuvant chemotherapy was associated with a decreased risk of mortality
      in stage III patients, consistent across all age cohorts, with the exception of
      the 90+ cohort, in whom adjuvant chemotherapy appeared to increase mortality.
      CONCLUSION: Administration of adjuvant chemotherapy for stage II/III colon cancer
      decreases with advancing age, but improved outcomes are seen in stage III
      patients under 90 years of age.

PMID- 30104157
TI  - Demographic transition - Cancer trends in geriatric population of North India.
AB  - Developing countries like India are witnessing a demographic transition resulting
      in population ageing. This population expansion will in future increase the
      burden of diseases more prevalent in older patients. Since cancer incidence
      increases with age, a surge in geriatric patients with cancer will soon
      overburden the health care system of our country. In anticipation of this change,
      present retrospective study done at a tertiary care centre highlights the cancer
      spectrum in all age groups with emphasis on geriatric patients. We stress upon
      the need for specialised care of these patients in India.

PMID- 30104158
TI  - Prognostic factors and first-line treatment modalities in nonagenarian patients
      with lung cancer.

PMID- 30104159
TI  - A concise predictive nomogram for renal artery stenosis in selective patients
      undergoing coronary angiography.
AB  - As reported scoring systems of renal artery stenosis (RAS) screening were not
      easily validated, we further proposed a simple method to predict or rule out RAS
      in selective patients undergoing coronary angiography (CAG). After preliminary
      inclusive criterion (severe hypertension or atherosclerosis, flash pulmonary
      edema, or unexplained renal dysfunction), 503 and 158 consecutive patients
      undergoing renal arteriography at the timing of CAG were separately enrolled
      between 2012 and 2015, and 2016 and 2017 as the development and validation
      cohort. A nomogram was derived from the multivariable logistic regression model,
      and its accuracy was assessed by the area under the receiver operating
      characteristic. Hypertension (odds ratio [OR] 17.92), estimated glomerular
      filtration rate <=72.66 mL/min.1.73 m2 (OR 2.75), early to late transmitral flow
      velocity ratio <=1.02 (OR 2.58) and low-density lipoprotein cholesterol <=3.17
      mmol/L (OR 1.85) were identified as independent predictors for RAS. The area
      under the curve of the nomogram in the development and validation cohort were
      0.754 (0.704, 0.804) and 0.772 (0.700, 0.844). The negative predictive value of
      hypertension (88.9%) was much higher than the other three predictors. The concise
      predictive nomogram can effectively estimate the probability of significant RAS
      during CAG. Along with normotensive, findings reported could easily evaluate RAS
      screening necessity based on clinical data.

PMID- 30104160
TI  - Adipose tissue-derived mesenchymal stromal cells for clinical application: An
      efficient isolation approach.
AB  - PURPOSE OF THE STUDY: Mesenchymal stromal cells (MSCs) are considered a promising
      tool for cell therapy approaches. The translation of research-based cell culture
      protocols into procedures that comply with Good Manufacturing Practice (GMP) is
      critical. The aim of this study was to design a new method for the expansion of
      MSCs from Adipose Tissue (AT-MSCs) in compliance with GMP, without enzymatic
      tissue digestion and without the use of animal proteins as source of growth
      factors. PATIENTS AND METHODS: MSCs were expanded from 10 periumbilical biopsies.
      Our new isolation approach is based on: (1) disruption of AT with an automated,
      closed system; (2) use of GMP-grade medium without the addition of fetal bovine
      serum or platelet lysate; (3) use of human recombinant Trypsin. AT-MSCs cultured
      in alpha-MEM and minced by scalpel were used as control. RESULTS: It was possible
      to expand MSCs from all the AT-samples for at least eight passages. MSCs
      displayed the typical spindle-shape morphology, a high viability, multilineage
      differentiation potential and high expression levels of the typical MSC-specific
      surface antigens and genes. Compared to standard method, MSCs obtained with the
      new method showed higher yield, up to passage 6, and higher purity in terms of
      percentage of CD34 and CD45 markers. All AT-MSCs exhibit in vitro
      immunosuppressive capacity and possess a normal karyotype. CONCLUSIONS: Our data
      clearly demonstrate that our new approach permits to generate AT-MSCs fully
      compliant for therapeutic use and better at least in terms of quantity and purity
      than those obtained with the standard method.

PMID- 30104161
TI  - Circulating Tumor Cells as a Biomarker of Survival and Response to Radium-223
      Therapy: Experience in a Cohort of Patients With Metastatic Castration-Resistant
      Prostate Cancer.
AB  - INTRODUCTION: Although increasing numbers of therapies with proven survival
      benefits have become available for metastatic castration-resistant prostate
      cancer (mCRPC), including radium-223, there is still a need for reliable
      biomarkers that provide information about clinically meaningful outcomes and
      treatment responses. MATERIALS AND METHODS: This study was a translational study
      that was conducted prospectively by the Spanish Oncology Genito-Urinary Group and
      included 45 patients with histologically confirmed mCRPC who were treated with
      radium-223. The primary response outcome was defined by a decline in circulating
      tumor cells (CTCs) of > 50% from baseline or a CTC count of <= 5 cells/7.5 mL at
      cycle 3 of radium-223. We also assessed response according to prostate-specific
      antigen and alkaline phosphatase levels. CTCs were evaluated as prognostic factor
      for treatment completion with radium-223 treatment. Kaplan-Meier estimates of
      survival were calculated for the global population and were correlated with
      biomarker response outcomes. RESULTS: Significantly, more patients with baseline
      CTC counts <= 5/7.5 mL, which are indicative of better prognoses, completed the 6
      injections of therapy than those with CTC counts > 5 (16/22; 73% vs. 6/20; 30%,
      respectively; P = .012). The median overall survival was 16 months. Survival was
      significantly decreased in patients with baseline CTC counts > 5 cells/7.5 mL (7
      months; P = .026) and baseline alkaline phosphatase levels >= 220 U/L (8 months;
      P = .028). CONCLUSIONS: CTCs hold significant promise as a prognostic factor for
      survival and completing treatment prior to the initiation of bone-targeted radium
      223 therapy. These findings may help to guide the use of radium-223 in patients
      with mCRPC.

PMID- 30104162
TI  - Patent foramen ovale and neurologic events in patients undergoing liver
      transplantation.
AB  - BACKGROUND: Patent foramen ovale (PFO) is present in approximately 20% of
      individuals. During liver transplantation (LT), intra-operative transesophageal
      echocardiography can observe transient intra-cardiac shunting of atheromatous
      debris via a PFO. Closure of PFOs prior to LT has thus been suggested as a
      potential treatment to reduce peri-operative cerebral vascular accident (CVA).
      The objective of this study was to assess if the presence of PFO is associated
      with CVA in patients undergoing LT. METHODS: Three hundred fifty-eight patients
      undergoing LT at a single academic institution were included. All patients
      underwent standardized cardiac evaluation including a detailed cardiovascular
      history and physical examination, electrocardiogram and transthoracic
      echocardiogram. Five patients were excluded because of poor transthoracic
      echocardiographic image quality, and three patients were excluded because of PFO
      closure prior to LT, yielding a study population of 350 patients. Medical records
      were reviewed to determine demographics, echocardiographic findings and outcome
      following LT. Major adverse cardiovascular events, myocardial infarction, CVA and
      death were collected. RESULTS: Mean age was 53.4 +/- 10.2 years; 61% male and 5%
      of patients had a prior history of CVA. Alcohol and hepatitis C were the most
      common etiologies for liver disease. Forty-six patients (13.1%) were diagnosed
      with PFO prior to LT. In-hospital CVA occurred in 6 patients (1.7%). The
      prevalence of a CVA was not significantly higher in patients with PFO compared to
      patients without PFO, 2.2% vs 1.6%, p = 0.57. In-hospital mortality was similar
      in patients with PFO compared to patients without PFO, 4.4% and 5.3%, p = 1.0.
      CONCLUSIONS: The presence of a PFO in patients undergoing LT is not associated
      with postoperative CVA. Prophylactic closure of PFOs, in the absence of other
      indications, does not appear to be warranted in patients undergoing LT.

PMID- 30104164
TI  - Endovascular treatment of posterior nutcracker syndrome with a new autoexpandable
      stent.
AB  - The endovascular treatment of nutcracker syndrome is currently considered by some
      to be the preferred treatment option in this pathologic process despite its
      risks. However, currently, there are few data about the pure endovascular
      approach in the posterior nutcracker syndrome related to evolution in the
      midterm. We present two successful cases of a complete endovascular approach in
      this disease, with follow-up of 9 months and 17 months without complications.

PMID- 30104165
TI  - Left iliac vein compression is not associated with infrainguinal deep venous
      thrombosis but is associated with iliac vein involvement.
AB  - OBJECTIVE: The purpose of this study was to investigate whether left iliac vein
      (LIV) compression had similar correlation with the risk of left iliac deep venous
      thrombosis (DVT; iliac vein involvement) and infrainguinal DVT (without iliac
      vein involvement). METHODS: A retrospective analysis of records and enhanced
      computed tomography images was conducted of 278 patients with left-sided DVT
      (iliac DVT, 228 patients; infrainguinal DVT, 50 patients) and 232 control
      patients without DVT on either side. The influences of LIV compression on the
      risk of left iliac DVT and infrainguinal DVT were investigated using logistic
      regression analysis. RESULTS: Mean percentage compression of the LIV in left
      iliac DVT (74.64% +/- 0.99%) patients was significantly higher than in non-DVT
      patients (53.42% +/- 1.49%; P < .01). However, mean percentage compression of the
      LIV in left infrainguinal DVT patients (45.37% +/- 2.71%) was significantly lower
      than in non-DVT patients (53.42% +/- 1.49%; P < .01). LIV compression was
      associated with increased odds of left iliac DVT (odds ratio, 1.88; 95%
      confidence interval, 1.64-2.15; P < .01) for each 10% increase in percentage
      compression of the LIV. However, LIV compression was not associated with
      increased odds of infrainguinal DVT (odds ratio, 0.89; 95% confidence interval,
      0.76-1.03; P = .126). CONCLUSIONS: Left iliac DVT patients had more severe LIV
      compression than left infrainguinal DVT patients did. LIV compression was not
      associated with development of left infrainguinal DVT, but it did correlate with
      the presence of left-sided DVT with iliac vein involvement.

PMID- 30104163
TI  - A neurobiological pathway to smoking in adolescence: TTC12-ANKK1-DRD2 variants
      and reward response.
AB  - The TTC12-ANKK1-DRD2 gene-cluster has been implicated in adult smoking. Here, we
      investigated the contribution of individual genes in the TTC12-ANKK1-DRD2 cluster
      in smoking and their association with smoking-associated reward processing in
      adolescence. A meta-analysis of TTC12-ANKK1-DRD2 variants and self-reported
      smoking behaviours was performed in four European adolescent cohorts (N =
      14,084). The minor G-allele of rs2236709, mapping TTC12, was associated with self
      reported smoking (p = 5.0 * 10-4) and higher plasma cotinine levels (p = 7.0 * 10
      5). This risk allele was linked to an increased ventral-striatal blood-oxygen
      level-dependent (BOLD) response during reward anticipation (n = 1,263) and with
      higher DRD2 gene expression in the striatum (p = 0.013), but not with TTC12 or
      ANKK gene expression. These data suggest a role for the TTC12-ANKK1-DRD2 gene
      cluster in adolescent smoking behaviours, provide evidence for the involvement of
      DRD2 in the early stages of addiction and support the notion that genetically
      driven inter-individual differences in dopaminergic transmission mediate reward
      sensitivity and risk to smoking.

PMID- 30104167
TI  - Changes in Adrenoceptor and GRK Expression in Patients With Chronic Pulmonary
      Regurgitation.
AB  - INTRODUCTION AND OBJECTIVES: Pulmonary regurgitation (PR) is a frequent
      complication after repair of congenital heart disease. Lymphocyte expression of
      adrenoceptors (beta1 and beta2) and kinases (GRK2, GRK3, and GRK5) reflects the
      neurohumoral changes that occur in heart failure (HF). The main objective of this
      study was to describe the gene expression of these molecules in circulating
      lymphocytes in patients with severe PR. METHODS: A prospective study was
      conducted to analyze lymphocyte expression of these molecules in patients with
      severe PR and compare it with expression in healthy controls and patients with
      advanced HF. RESULTS: We studied 35 patients with severe PR, 22 healthy controls,
      and 13 patients with HF. Multiple comparisons analysis showed that beta2
      adrenoceptor gene expression levels were higher in the control group than in
      patients in the PR and HF groups and that expression in the latter 2 groups was
      similar (748.49 [rank 1703.87] vs 402.80 [rank 1210.81] vs 287.46 [rank 685.69] P
      = .001). Similar findings were obtained in gene expression of GRK2 (760.89 [rank
      1169.46] vs 445.17 [rank 1190.69] vs 284.09 [rank 585.27] P < .001). There were
      no differences in expression levels of these molecules according to clinical
      variables in patients with PR. CONCLUSIONS: The gene expression pattern of GRK2
      and beta2-adrenoceptor as molecular markers of cardiac dysfunction was altered in
      patients with severe PR compared with controls and was similar to expression in
      patients with advanced HF.

PMID- 30104168
TI  - Should A Couple with Failed In Vitro Fertilization/Intracytoplasmic Sperm
      Injection and Increased Sperm DNA Fragmentation Use Testicular Sperm for the Next
      Cycle?
AB  - Limited observational data purporting a benefit of testicular sperm for
      intracytoplasmic sperm injection failure do not provide sufficient evidence. The
      first step is to reduce sperm DNA fragmentation in ejaculated sperm through
      lifestyle modifications, antioxidant therapy, or treatment of underlying
      abnormalities such as infection or varicocele.

PMID- 30104166
TI  - Co-storage and release of insulin-like peptide-5, glucagon-like peptide-1 and
      peptideYY from murine and human colonic enteroendocrine cells.
AB  - OBJECTIVE: Insulin-like peptide-5 (INSL5) is an orexigenic gut hormone found in a
      subset of colonic and rectal enteroendocrine L-cells together with the
      anorexigenic hormones glucagon-like peptide-1 (GLP-1) and peptideYY (PYY). Unlike
      GLP-1 and PYY, INSL5 levels are elevated by calorie restriction, raising
      questions about how these hormones respond to different stimuli when they arise
      from the same cell type. The aim of the current study was to identify whether and
      how INSL5, GLP-1 and PYY are co-secreted or differentially secreted from colonic
      L-cells. METHODS: An inducible reporter mouse (Insl5-rtTA) was created to enable
      selective characterisation of Insl5-expressing cells. Expression profiling and
      Ca2+-dynamics were assessed using TET-reporter mice. Secretion of INSL5, PYY, and
      GLP-1 from murine and human colonic crypt cultures was quantified by tandem mass
      spectrometry. Vesicular co-localisation of the three hormones was analysed in 3D
      SIM images of immunofluorescently-labelled murine colonic primary cultures and
      tissue sections. RESULTS: INSL5-producing cells expressed a range of G-protein
      coupled receptors previously identified in GLP-1 expressing L-cells, including
      Ffar1, Gpbar1, and Agtr1a. Pharmacological or physiological agonists for these
      receptors triggered Ca2+ transients in INSL5-producing cells and stimulated INSL5
      secretion. INSL5 secretory responses strongly correlated with those of PYY and
      GLP-1 across a range of stimuli. The majority (>80%) of secretory vesicles co
      labelled for INSL5, PYY and GLP-1. CONCLUSIONS: INSL5 is largely co-stored with
      PYY and GLP-1 and all three hormones are co-secreted when INSL5-positive cells
      are stimulated. Opposing hormonal profiles observed in vivo likely reflect
      differential stimulation of L-cells in the proximal and distal gut.

PMID- 30104169
TI  - Changing the treatment landscape for latent tuberculosis with rifampicin.

PMID- 30104170
TI  - Surgical outcomes between patients with and without a cirrhotic liver undergoing
      laparoscopic liver resection: A meta-analysis.
AB  - BACKGROUND: Laparoscopic surgery in patients with liver cirrhosis (CL) is
      considered to be challenging. Recent studies have shown that laparoscopic liver
      resection (LLR) is more beneficial of reduced operative stress and postoperative
      complications in patients with CL. AIM: A meta-analysis was done to review the
      currently available published data comparing LLR for patients with CL versus
      those non-cirrhosis of the liver (NCL). METHODS: The electronic databases of
      PubMed, Wiley, Web of Science, Embase, and the Cochrane Library were searched
      from date of inception to January 29, 2018. Studies reporting a comparison of
      outcomes and methods of LLR in CL and NCL groups were included. The studies were
      evaluated using the modified Newcastle-Ottawa Scale. RESULTS: A total of 1573
      patients from six cohort studies were included in final analysis. The CL group
      had a slightly shorter operative time compared with the NCL group (weighted mean
      difference [WMD], 18.78min shorter; 95% confidence interval [CI], -43.54-5.98;
      P=0.14) and delayed hospital stay (WMD, 1.26 days longer; 95% CI, -0.05-2.56;
      P=0.06). Blood loss, blood transfusion rate, mortality, and conversion rate did
      not differ significantly between the groups. CONCLUSIONS: LLR is safe and
      feasible in the CL compared with the NCL groups. Our present review indicates
      that LLR should be considered when selecting surgery for patients with CL.

PMID- 30104172
TI  - Women's views and experiences of publicly-funded homebirth programs in Victoria,
      Australia: A cross-sectional survey.
AB  - BACKGROUND: It is critical women's voices are heard if there is to be more
      widespread implementation of midwifery-led continuity models. Publicly-funded
      homebirth is one such model, yet there has been limited systematic evaluation
      from the women's perspective. AIM: Examine women's experiences of and views about
      the two publicly-funded homebirth programs in Victoria, Australia. METHODS: A
      cross-sectional design was used. All eligible women enrolled in the two pilot
      homebirth programs in metropolitan Melbourne whose infants were eight weeks of
      age or more during the evaluation period were invited to participate in a postal
      survey. A structured questionnaire was used, with some open-ended questions to
      enable extra comments. We explored women's reasons for choosing homebirth; views
      of care; experience of labour and birth; views on transfer; and overall
      experience of the homebirth program. Data were analysed using descriptive
      statistics. Simple thematic analysis was used for open-ended questions. FINDINGS:
      The survey response rate was 71% (96/136). A high percentage of women rated their
      care as 'Very good': pregnancy 81%; labour and birth 90%; and the early
      postpartum period 83%. Women reported low levels of anxiety during labour and
      birth, were able to express their feelings, felt in control, and coped physically
      and emotionally better than they had expected. They felt well supported by
      midwives and overall reported very positive experiences of the homebirth
      programs. CONCLUSIONS: These two publicly-funded homebirth pilot programs
      demonstrated very positive care ratings by women. These findings, along with the
      clinical outcomes (reported separately), support the continuation and expansion
      of the program.

PMID- 30104171
TI  - Hypersensitivity Reactions to Antiepileptic Drugs in Children: Epidemiologic,
      Pathogenetic, Clinical, and Diagnostic Aspects.
AB  - Epilepsy affects approximately 10 million children globally. Antiepileptic drugs
      (AEDs) are among the most frequent causes of drug hypersensitivity reactions
      (DHRs), especially severe ones. However, systematic studies about AED
      hypersensitivity among children are very rare. In this review, we aimed to gather
      all relevant and important data about different aspects of DHRs to AEDs in
      children by conducting a PubMed search including English-language studies
      published between January 1990 and June 2017. In these studies, aromatic AEDs
      were mostly incriminated in DHRs, but still being dominantly prescribed in both
      developed and developing countries. Although newer AEDs were increasingly
      prescribed owing to their presumed low toxicity profile, surveillance of DHRs is
      strongly recommended because case reports about severe reactions were recently
      reported. The pathogenesis seemed to be multifactorial including metabolic,
      genetic, and immunologic factors. Recent pharmacogenomic studies demonstrated
      strong genetic associations between some human leucocyte antigens and/or
      polymorphisms of AED metabolic enzymes and AED-induced DHRs among both adults and
      children. Young children, concurrent medications, a high starting dose and rapid
      dose escalation, and some genetic markers are important risk factors for AED
      induced hypersensitivity. There were a very limited number of studies in the
      pediatric population evaluating the efficacy of different available diagnostic
      tools, such as intradermal, patch, and drug provocation tests. Data including
      mostly adult patients showed that patch tests had relatively high diagnostic
      value to identify the culprit with a positivity rate that ranged between 19.7%
      and 100% in delayed reactions to AEDs. Clinical cross-reactivity rates of 15% to
      70% have been reported mainly between aromatic AEDs. In selected cases, where
      there is no other option, desensitization can be considered, although experience
      in children remained limited.

PMID- 30104173
TI  - Initiation and duration of breastfeeding of Aboriginal infants in South
      Australia.
AB  - BACKGROUND: Benefits of breastfeeding are well-established. Few studies have
      examined initiation and duration of breastfeeding of Aboriginal infants. METHODS:
      Population-based study of women giving birth to an Aboriginal infant in South
      Australia, July 2011-June 2013. FINDINGS: 344 women took part. Participants were
      representative in relation to maternal age, infant birthweight and gestation.
      Eighty-six percent initiated breastfeeding, declining to 54% at 12 weeks
      postpartum. Women living in remote areas were more likely to be breastfeeding at
      12 weeks than women living in Adelaide (Odds Ratio=2.6, 95% Confidence Interval
      1.5-4.7). Two-thirds of women (67%) attending standard public antenatal care in
      regional areas and 61% attending regional Aboriginal Family Birthing Program
      Services were breastfeeding at 12 weeks, compared to one third of women (36%)
      attending standard metropolitan public antenatal care and 49% of women attending
      metropolitan Aboriginal Family Birthing Program Services. Less than half of women
      (45%) described their postnatal care as 'very good', and 40% were not always able
      to access support with infant feeding when needed. The most common reasons for
      switching to formula before 6 weeks were: low milk supply/baby not gaining
      weight, mastitis/sore breasts or other feeding problems. Mothers also identified
      their own health as a factor. CONCLUSION: While the findings must be treated with
      caution due to small numbers, they suggest benefits for women attending
      Aboriginal Family Birthing Program services in the urban environment where rates
      of initiation and continued breastfeeding are lowest. Provision of culturally
      appropriate support to Aboriginal women during and after pregnancy is key to
      improving outcomes.

PMID- 30104174
TI  - What's in wine? A clinician's perspective.
AB  - Alcoholic beverages, specifically wine, have been consumed for many years. Wine
      is postulated to play an important role in the improvement of cardiovascular risk
      factors. Most epidemiological studies have found sustained consumption at light
      to-moderate amounts to increase HDL cholesterol, reduce platelet aggregation, and
      promote fibrinolysis. Wine consumption has been inversely associated with
      ischemic heart disease, and the alcohol-blood pressure association, in most
      studies, follows a J-shaped curve. These outcomes have been attributed to the
      molecular constituents of wine, namely ethanol and polyphenols. Due to the
      continued interest in wine as a biological beverage, we review the chemistry of
      wine as clinicians, including its chemical composition, viticulture and
      enological practices, and other chemical factors that influence the bioactive
      components of wine. We also outline the biological effects of wine components and
      directions for future research.

PMID- 30104175
TI  - A serological scoring system to predict lymph node metastasis in patients with
      hepatocellular carcinoma.
AB  - BACKGROUND: Lymph node metastasis (LNM)has widely been recognized as a poor
      prognostic indicator for hepatocellular carcinoma (HCC) patients. Preoperative
      prediction of LNM is important for clinicians to decide on treatment. This study
      was designed to develop a simple and convenient system to predict LNM. METHODS:
      Consecutive HCC patients who were suspected to have LNM were divided into a
      training, an internal validation and an external validation cohort. The receiver
      operating characteristic (ROC) analysis was used to determine the threshold value
      of the preoperative serological variables. A nomogram visualization system model
      was then established. RESULT: Of the 287 patients, there were 31 patients who had
      LNM (10.8%), and 21 of 203 patients (10.3%) were in the training cohort and 10 of
      84 patients (11.9%) in the internal validation cohort. Sixteen of 176 patients
      (9.1%) in the external validation cohort had LNM. The serological indices
      including neutrophil/lymphocyte rate, age, platelet, prothrombin time, and total
      protein, were included in the nomogram. The areas of the ROC curve were 0.846,
      0.679 and 0.738 in predicting LNM in the training cohort, the internal validation
      cohort and the external validation cohort, respectively. CONCLUSION: The scoring
      system constructed using the preoperative serological variables predicted LNM in
      HCC patients.

PMID- 30104178
TI  - PrEP and the PrEPstars.

PMID- 30104176
TI  - A Novel Combination of the mTORC1 Inhibitor Everolimus and the Immunomodulatory
      Drug Lenalidomide Produces Durable Responses in Patients With Heavily Pretreated
      Relapsed Lymphoma.
AB  - BACKGROUND: Treatment outcomes have improved in lymphoid malignancies but relapse
      remains inevitable for most patients. Everolimus and lenalidomide have shown
      clinical activity as single agents in patients with relapsed and refractory
      Hodgkin and non-Hodgkin lymphomas. PATIENTS AND METHODS: The present phase I/II
      trial for patients with relapsed and refractory lymphoid malignancy opened at
      Mayo Clinic from January 2011 to May 2013. The trial used a standard cohort 3 + 3
      design to determine the maximum tolerated dose for the combination. Stem cell
      transplantation had failed in 27 of the patients (49%), 63% had stage IV disease,
      and >= 3 previous therapies had failed in 78%. RESULTS: Of the 58 patients,
      enrolled, 55 were evaluable for analysis. The maximum tolerated dose was 5 mg/d
      for everolimus plus 10 mg/d for 21 days for lenalidomide. The most common grade
      >= 3 toxicities were hematologic and included neutropenia (56%), leukopenia
      (38%), and thrombocytopenia (33%). Seven patients discontinued the study because
      of adverse events. One patient died of disease progression. The overall response
      rate was 27% (15 of 55), with 38% (21 of 55) having stable disease. CONCLUSION:
      The present phase I/II trial of everolimus and lenalidomide for R/R lymphoma has
      shown the combination to be tolerable, with neutropenia as the main dose-limiting
      toxicity. Encouraging responses were seen in this heavily pretreated group, and
      the patients with a response had meaningful duration of response.

PMID- 30104179
TI  - This is a story about living-not dying.

PMID- 30104177
TI  - Outcome of Patients With Newly Diagnosed Systemic Light-Chain Amyloidosis
      Associated With Deletion of 17p.
AB  - INTRODUCTION: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but
      its significance in light-chain amyloidosis is unknown. PATIENTS AND METHODS: We
      identified patients with light-chain amyloidosis and del 17p at diagnosis, and
      analyzed presenting characteristics, treatments, and clinical outcomes. All had
      baseline biopsy results showing amyloid and serologic and marrow studies,
      including standard fluorescence in-situ hybridization determinations of del 17p
      using commercial probes. Consensus criteria for hematologic and organ
      involvement, progression, and response were used. Kaplan-Meier (log rank)
      analyses and Cox regression analysis of baseline variables were used to identify
      predictors of overall and progression-free survival (PFS). Six-month landmark
      analyses were performed to assess the impact of treatment-related variables.
      RESULTS: We identified 44 patients from 7 countries with median marrow and del
      17p plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent
      had cardiac involvement, including 44% stage III. Two-thirds of the patients
      initially received bortezomib-based therapy. Forty-nine percent of patients
      experienced complete response or very good partial response, with median time to
      best response of 4 months (range, 1-28 months). Median overall survival and PFS
      were 49 and 32 months. Cardiac stage and hematologic response were the key
      predictors of outcomes. Patients with > 50% and <= 50% del 17p in clonal plasma
      cells had median survivals of 28 and 52 months, respectively (P = .08). In
      landmark analyses, only hematologic response predicted both overall survival and
      PFS. CONCLUSION: Cardiac stage, hematologic response, and del 17p percentage
      impact outcomes in these cases. Emphasis should be placed on optimizing
      supportive care and achieving a deep hematologic response.

PMID- 30104180
TI  - Circulating tumor cells detection in neuroblastoma patients by EpCAM-independent
      enrichment and immunostaining-fluorescence in situ hybridization.
AB  - Detecting circulating tumor cells (CTCs) has proven valuable for evaluating the
      prognosis of cancer patients and for studying the mechanisms of treatment
      resistance. Owing to the lack of universal and specific tumor markers for
      neuroblastoma (NB), in this prospective study, we adopted an EpCAM-independent
      method to detect CTCs in the peripheral blood of NB patients. We used an EpCAM
      independent assay to delete leukocytes and to enrich the CTCs. CTCs were
      identified by immunostaining of CD45, DAPI and DNA fluorescence in situ
      hybridization (FISH) of the centromere of chromosome 8 probe (CEP8). Cells that
      were DAPI+/CD45-/CEP8 >= 3 were considered CTCs. We collected peripheral blood
      from 28 NB patients as well as clinical and follow-up data. The number of CTCs
      among the different risk groups were significantly different (p = .0208, Kruskal
      Wallis test). Patients with metastasis had more CTCs than those without
      metastasis (p < .0001, Mann-Whitney test). Patients with >=3 CTCs per 4 ml of
      peripheral blood had an increased likelihood of having metastasis (sensitivity,
      88.89%; specificity, 78.59%), and patients with >=10 CTCs per 4 ml of peripheral
      blood had poorer overall survival. The EpCAM-independent assay along with
      immunostaining-FISH (i-FISH) described here can detect CTCs in patients with NB
      at a high sensitivity and may have clinical value for prognosis evaluation and
      diagnosing metastasis when imaging data are ambiguous.

PMID- 30104181
TI  - Neurotensin contributes to pediatric intestinal failure-associated liver disease
      via regulating intestinal bile acids uptake.
AB  - Although the pathogenesis of intestinal failure (IF)-associated liver disease
      (IFALD) is uncertain, IF-associated cholestasis mediated by the combination of
      intestinal injury and parenteral nutrition (PN) can lead to disturbed hepatocyte
      bile acids (BA) homeostasis and cause liver damages. We here show that
      neurotensin (NT; also known as NTS) concentrations were lower compared to healthy
      matched controls. Patients with cholestasis [56.1 ng/L (9.7-154.7) vs. 210.4 ng/L
      (134-400.4), p < .001] had lower serum NT concentrations than others. In
      patients' ileum, the levels of NT mRNA were positively correlated with the apical
      sodium dependent bile acid transporter (ASBT) mRNA levels. In mice and in
      cultured intestinal cells, NT treatments stimulated the expression of ASBT and
      led to increase BA uptake via NT receptors (NTR1 and NTR3; also known as NTSR1and
      NTSR3). In conclusion, these findings directly link NT with BA homeostasis, which
      provide an insight into the complex mechanisms mediating the development of liver
      disease in pediatric patients with IF.

PMID- 30104182
TI  - Cross-Jurisdictional Data Exchange Impact on the Estimation of the HIV Population
      Living in the District of Columbia: Evaluation Study.
AB  - BACKGROUND: Accurate HIV surveillance data are essential to monitor trends to
      help end the HIV epidemic. Owing to strict policies around data security and
      confidentiality, HIV surveillance data have not been routinely shared across
      jurisdictions except a biannual case-by-case review process to identify and
      remove duplicate cases (Routine Interstate Duplicate Review, RIDR). HIV
      surveillance estimates for the District of Columbia (DC) are complicated by
      migration and care seeking throughout the metropolitan area, which includes
      Maryland and Virginia. To address gaps in HIV surveillance data, health
      departments of DC, Maryland, and Virginia have established HIV surveillance data
      sharing agreements. Although the Black Box (a privacy data integration tool
      external to the health departments) facilitates the secure exchange of data
      between DC, Maryland, and Virginia, its previous iterations were limited by the
      frequency and scope of information exchanged. The health departments of DC,
      Maryland, and Virginia engaged in data sharing to further improve HIV
      surveillance estimates. OBJECTIVE: This study assessed the impact of cross
      jurisdictional data sharing on the estimation of people living with HIV in DC and
      reduction of cases in the RIDR process. METHODS: Data sharing agreements
      established in 2014 allowed for the exchange of HIV case information (eg, current
      residential address) and laboratory information (eg, test types, result dates,
      and results) from the enhanced HIV/AIDS Reporting System (eHARS). Regular data
      exchanges began in 2017. The participating jurisdictions transferred data (via
      secure file transfer protocol) for individuals having a residential address in a
      partnering jurisdiction at the time of HIV diagnosis or evidence of receiving HIV
      related services at a facility located in a partnering jurisdiction. The DC
      Department of Health compared the data received to DC eHARS and imported updated
      data that matched existing cases. Evaluation of changes in current residential
      address and HIV prevalence was conducted by comparing data before and after HIV
      surveillance data exchanges. RESULTS: After the HIV surveillance data exchange,
      an average of 396 fewer cases were estimated to be living in DC each year from
      2012 to 2016. Among cases with a residential status change, 66.4% (1316/1982) had
      relocated to Maryland and 19.8% (392/1982) to Virginia; majority of these had
      relocated to counties bordering DC. Relocation in and out of DC differed by mode
      of transmission, race and ethnicity, age group, and gender. After data exchange,
      the volume of HIV cases needing RIDR decreased by 74% for DC-Maryland and 81% for
      DC-Virginia. CONCLUSIONS: HIV surveillance data exchange between the public
      health departments of DC, Maryland, and Virginia reduced the number of cases
      misclassified as DC residents and reduced the number of cases needing RIDR.
      Continued data exchanges will enhance the ability of DC Department of Health to
      monitor the local HIV epidemic.

PMID- 30104183
TI  - mHealth Self-Report Monitoring in Competitive Middle- and Long-Distance Runners:
      Qualitative Study of Long-Term Use Intentions Using the Technology Acceptance
      Model.
AB  - BACKGROUND: International middle- and long-distance running competitions attract
      millions of spectators in association with city races, world championships, and
      Olympic Games. It is therefore a major concern that ill health and pain, as a
      result of sports overuse, lead to numerous hours of lost training and decreased
      performance in competitive runners. Despite its potential for sustenance of
      performance, approval of mHealth self-report monitoring (mHSM) in this group of
      athletes has not been investigated. OBJECTIVE: The objective of our study was to
      explore individual and situational factors associated with the acceptance of long
      term mHSM in competitive runners. METHODS: The study used qualitative research
      methods with the Technology Acceptance Model as the theoretical foundation. The
      study population included 20 middle- and long-distance runners competing at
      national and international levels. Two mHSM apps asking for health and training
      data from track and marathon runners were created on a platform for web survey
      development (Briteback AB). Data collection for the technology acceptance
      analysis was performed via personal interviews before and after a 6-week
      monitoring period. Preuse interviews investigated experience and knowledge of
      mHealth monitoring and thoughts on benefits and possible side effects. The
      postuse interviews addressed usability and usefulness, attitudes toward
      nonfunctional issues, and intentions to adhere to long-term monitoring. In
      addition, the runners' trustworthiness when providing mHSM data was discussed.
      The interview data were investigated using a deductive thematic analysis.
      RESULTS: The mHSM apps were considered technically easy to use. Although the
      runners read the instructions and entered data effortlessly, some still perceived
      mHSM as problematic. Concerns were raised about the selection of items for
      monitoring (eg, recording training load as running distance or time) and about
      interpretation of concepts (eg, whether subjective well-being should encompass
      only the running context or daily living on the whole). Usefulness of specific
      mHSM apps was consequently not appraised on the same bases in different
      subcategories of runners. Regarding nonfunctional issues, the runners competing
      at the international level requested detailed control over who in their sports
      club and national federation should be allowed access to their data; the less
      competitive runners had no such issues. Notwithstanding, the runners were willing
      to adhere to long-term mHSM, provided the technology was adjusted to their
      personal routines and the output was perceived as contributing to running
      performance. CONCLUSIONS: Adoption of mHSM by competitive runners requires clear
      definitions of monitoring purpose and populations, repeated in practice tests of
      monitoring items and terminology, and meticulousness regarding data-sharing
      routines. Further naturalistic studies of mHSM use in routine sports practice
      settings are needed with nonfunctional ethical and legal issues included in the
      evaluation designs.

PMID- 30104184
TI  - Correlations Between Objective Behavioral Features Collected From Mobile and
      Wearable Devices and Depressive Mood Symptoms in Patients With Affective
      Disorders: Systematic Review.
AB  - BACKGROUND: Several studies have recently reported on the correlation between
      objective behavioral features collected via mobile and wearable devices and
      depressive mood symptoms in patients with affective disorders (unipolar and
      bipolar disorders). However, individual studies have reported on different and
      sometimes contradicting results, and no quantitative systematic review of the
      correlation between objective behavioral features and depressive mood symptoms
      has been published. OBJECTIVE: The objectives of this systematic review were to
      (1) provide an overview of the correlations between objective behavioral features
      and depressive mood symptoms reported in the literature and (2) investigate the
      strength and statistical significance of these correlations across studies. The
      answers to these questions could potentially help identify which objective
      features have shown most promising results across studies. METHODS: We conducted
      a systematic review of the scientific literature, reported according to the
      preferred reporting items for systematic reviews and meta-analyses guidelines.
      IEEE Xplore, ACM Digital Library, Web of Sciences, PsychINFO, PubMed, DBLP
      computer science bibliography, HTA, DARE, Scopus, and Science Direct were
      searched and supplemented by hand examination of reference lists. The search
      ended on April 27, 2017, and was limited to studies published between 2007 and
      2017. RESULTS: A total of 46 studies were eligible for the review. These studies
      identified and investigated 85 unique objective behavioral features, covering 17
      various sensor data inputs. These features were divided into 7 categories.
      Several features were found to have statistically significant and consistent
      correlation directionality with mood assessment (eg, the amount of home stay,
      sleep duration, and vigorous activity), while others showed directionality
      discrepancies across the studies (eg, amount of text messages [short message
      service] sent, time spent between locations, and frequency of mobile phone screen
      activity). CONCLUSIONS: Several studies showed consistent and statistically
      significant correlations between objective behavioral features collected via
      mobile and wearable devices and depressive mood symptoms. Hence, continuous and
      everyday monitoring of behavioral aspects in affective disorders could be a
      promising supplementary objective measure for estimating depressive mood
      symptoms. However, the evidence is limited by methodological issues in individual
      studies and by a lack of standardization of (1) the collected objective features,
      (2) the mood assessment methodology, and (3) the statistical methods applied.
      Therefore, consistency in data collection and analysis in future studies is
      needed, making replication studies as well as meta-analyses possible.

PMID- 30104185
TI  - Comparing the Data Quality of Global Positioning System Devices and Mobile Phones
      for Assessing Relationships Between Place, Mobility, and Health: Field Study.
AB  - BACKGROUND: Mobile devices are increasingly used to collect location-based
      information from individuals about their physical activities, dietary intake,
      environmental exposures, and mental well-being. Such research, which typically
      uses wearable devices or mobile phones to track location, benefits from the
      growing availability of fine-grained data regarding human mobility. However,
      little is known about the comparative geospatial accuracy of such devices.
      OBJECTIVE: In this study, we compared the data quality of location information
      collected from two mobile devices that determine location in different ways-a
      global positioning system (GPS) watch and a mobile phone with Google's Location
      History feature enabled. METHODS: A total of 21 chronically ill participants
      carried both devices, which generated digital traces of locations, for 28 days. A
      mobile phone-based brief ecological momentary assessment (EMA) survey asked
      participants to manually report their location at 4 random times throughout each
      day. Participants also took part in qualitative interviews and completed surveys
      twice during the study period in which they reviewed recent mobile phone and
      watch trace data to compare the devices' trace data with their memory of their
      activities on those days. Trace data from the devices were compared on the basis
      of (1) missing data days, (2) reasons for missing data, (3) distance between the
      route data collected for matching day and the associated EMA survey locations,
      and (4) activity space total area and density surfaces. RESULTS: The watch
      resulted in a much higher proportion of missing data days (P<.001), with missing
      data explained by technical differences between the devices as well as
      participant behaviors. The mobile phone was significantly more accurate in
      detecting home locations (P=.004) and marginally more accurate (P=.07) for all
      types of locations combined. The watch data resulted in a smaller activity space
      area and more accurately recorded outdoor travel and recreation. CONCLUSIONS: The
      most suitable mobile device for location-based health research depends on the
      particular study objectives. Furthermore, data generated from mobile devices,
      such as GPS phones and smartwatches, require careful analysis to ensure quality
      and completeness. Studies that seek precise measurement of outdoor activity and
      travel, such as measuring outdoor physical activity or exposure to localized
      environmental hazards, would benefit from the use of GPS devices. Conversely,
      studies that aim to account for time within buildings at home or work, or those
      that document visits to particular places (such as supermarkets, medical
      facilities, or fast food restaurants), would benefit from the greater precision
      demonstrated by the mobile phone in recording indoor activities.

PMID- 30104187
TI  - Individual risk prediction using data beyond the medical clinic.

PMID- 30104186
TI  - A Remote Intervention to Prevent or Delay Cognitive Impairment in Older Adults:
      Design, Recruitment, and Baseline Characteristics of the Virtual Cognitive Health
      (VC Health) Study.
AB  - BACKGROUND: A growing body of evidence supports the use of lifestyle
      interventions for preventing or delaying the onset of Alzheimer disease and other
      forms of dementia in at-risk individuals. The development of internet-delivered
      programs would increase the scalability and reach of these interventions, but
      requires validation to ensure similar effectiveness to brick-and-mortar options.
      OBJECTIVE: We describe the study design, recruitment process, and baseline
      participant characteristics of the sample in the Virtual Cognitive Health (VC
      Health) study. Future analyses will assess the impact of the remotely delivered
      lifestyle intervention on (1) cognitive function, (2) depression and anxiety, and
      (3) various lifestyle behaviors, including diet, exercise, and sleep, in a cohort
      of older adults with subjective memory decline. Additional analyses will explore
      feasibility outcomes, as well as the participants' engagement patterns with the
      program. METHODS: Older adults (aged 60-75 years) with subjective memory decline
      as measured by the Subjective Cognitive Decline 9-item (SCD-9) questionnaire, and
      who reported feeling worried about their memory decline, were eligible to
      participate in this single-arm pre-post study. All participants enrolled in the
      yearlong digital intervention, which consists of health coach-guided lifestyle
      change for improving diet, exercise, sleep, stress, and cognition. All components
      of this study were conducted remotely, including the collection of data and the
      administration of the intervention. We assessed participants at baseline, 12
      weeks, 24 weeks, and 52 weeks with online surveys and the Repeatable Battery for
      the Assessment of Neuropsychological Status (RBANS) test. We will conduct
      intention-to-treat analysis on all outcomes. RESULTS: A total of 85 participants
      enrolled in the intervention and 82 are included in the study sample (3
      participants withdrew). The study cohort of 82 participants comprises 61 (74%)
      female, 72 (88%) white, and 64 (78%) overweight or obese participants, and 55
      (67%) have at least a college degree. The average baseline RBANS score was 95.9
      (SD 11.1), which is within age-adjusted norms. The average SCD-9 score was 6.0
      (SD 2.0), indicating minor subjective cognitive impairment at the beginning of
      the study. The average baseline Generalized Anxiety Disorder 7-item scale score
      was 6.2 (SD 4.5), and the average Patient Health Questionnaire 9-item score was
      8.5 (SD 4.9), indicating mild levels of anxiety and depression at baseline.
      CONCLUSIONS: Internet-delivered lifestyle interventions are a scalable solution
      for the prevention or delay of Alzheimer disease. The results of this study will
      provide the first evidence for the effectiveness of a fully remote intervention
      and lay the groundwork for future investigations. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT02969460; http://clinicaltrials.gov/ct2/show/NCT02969460
      (Archived by WebCite at http://www.webcitation.org/71LkYAkSh). REGISTERED REPORT
      IDENTIFIER: RR1-10.2196/11368.

PMID- 30104188
TI  - Rapid repeat pregnancy among women with intellectual and developmental
      disabilities: a population-based cohort study.
AB  - BACKGROUND: Rapid repeat pregnancy within 12 months of a live birth is associated
      with adverse perinatal outcomes. We evaluated the risk for rapid repeat pregnancy
      among women with intellectual and developmental disabilities, with whom sharing
      of information about pregnancy planning and contraception may be inadequate.
      METHODS: We accessed population-based health administrative data for all women
      with an index live birth in Ontario, Canada, for the period 2002-2013. We used
      modified Poisson regression to compare relative risks (RRs) for a rapid repeat
      pregnancy within 12 months of the index live birth in women with and without
      intellectual and developmental disabilities, first adjusting for demographic
      factors and then additionally adjusting for social, health and health care
      disparities. RESULTS: We compared 2855 women with intellectual and developmental
      disabilities and 923 367 women without such disabilities. At the index live
      birth, women with intellectual and developmental disabilities were more likely to
      be younger than 25 years of age (46.8% v. 18.2%) and to be disadvantaged on each
      measure of social, health and health care disparities. These women had a higher
      rate of rapid repeat pregnancy than those without such disabilities (7.6% v.
      3.9%; adjusted RR 1.34, 95% confidence interval [CI] 1.18-1.54, after controlling
      for demographic factors). This risk was attenuated upon further adjustment for
      social, health and health care disparities (adjusted RR 1.00, 95% CI 0.87-1.14).
      INTERPRETATION: Rapid repeat pregnancy, which was more common among women with
      intellectual and developmental disabilities, may be explained by social, health
      and health care disparities. To optimize reproductive health, multifactorial
      approaches to address the marginalization experienced by this population are
      likely needed.

PMID- 30104189
TI  - Aligning innovations in health funding with innovations in care.

PMID- 30104190
TI  - Reversible cerebellar neurotoxicity induced by metronidazole.

PMID- 30104191
TI  - Setting the record straight on taxation and disparities in smoking.

PMID- 30104192
TI  - When the perfect is the enemy of the good.

PMID- 30104194
TI  - Pre-residency boot camps calm medical graduate jitters.

PMID- 30104193
TI  - The need for Canada to tax sugar-sweetened beverages.

PMID- 30104195
TI  - More doctors talking about nonclinical careers, but challenges remain.

PMID- 30104196
TI  - Canada among top 20 countries for skin cancer risk.

PMID- 30104197
TI  - Microscale and Nanoscale Electrophotonic Diagnostic Devices.
AB  - Detecting and identifying infectious agents and potential pathogens in complex
      environments and characterizing their mode of action is a critical need.
      Traditional diagnostics have targeted a single characteristic (e.g., spectral
      response, surface receptor, mass, intrinsic conductivity, etc.). However,
      advances in detection technologies have identified emerging approaches in which
      multiple modes of action are combined to obtain enhanced performance
      characteristics. Particularly appealing in this regard, electrophotonic devices
      capable of coupling light to electron translocation have experienced rapid recent
      growth and offer significant advantages for diagnostics. In this review, we
      explore three specific promising approaches that combine electronics and
      photonics: (1) assays based on closed bipolar electrochemistry coupling electron
      transfer to color or fluorescence, (2) sensors based on localized surface plasmon
      resonances, and (3) emerging nanophotonics approaches, such as those based on
      zero-mode waveguides and metamaterials.

PMID- 30104198
TI  - Ras-Specific GTPase-Activating Proteins-Structures, Mechanisms, and Interactions.
AB  - Ras-specific GTPase-activating proteins (RasGAPs) down-regulate the biological
      activity of Ras proteins by accelerating their intrinsic rate of GTP hydrolysis,
      basically by a transition state stabilizing mechanism. Oncogenic Ras is commonly
      not sensitive to RasGAPs caused by interference of mutants with the electronic or
      steric requirements of the transition state, resulting in up-regulation of
      activated Ras in respective cells. RasGAPs are modular proteins containing a
      helical catalytic RasGAP module surrounded by smaller domains that are frequently
      involved in the subcellular localization or contributing to regulatory features
      of their host proteins. In this review, we summarize current knowledge about
      RasGAP structure, mechanism, regulation, and dual-substrate specificity and
      discuss in some detail neurofibromin, one of the most important negative Ras
      regulators in cellular growth control and neuronal function.

PMID- 30104200
TI  - Rethinking Gamma-secretase Inhibitors for Treatment of Non-small-Cell Lung
      Cancer: Is Notch the Target?
AB  - Lung cancer is the leading cause of cancer-related deaths among men and women.
      gamma-Secretase inhibitors, a class of small-molecule compounds that target the
      Notch pathway, have been tested to treat non-small-cell lung cancer (NSCLC) in
      preclinical and clinical trials. Although gamma-secretase inhibitors elicit a
      response in some tumors as single agents and sensitize NSCLC to cytotoxic and
      targeted therapies, they have not yet been approved for NSCLC therapy. We discuss
      our recently published preclinical study using the gamma-secretase inhibitor
      AL101, formerly BMS906024, on cell lines and PDX models of NSCLC, primarily lung
      adenocarcinoma. We propose that Notch pathway mutations may not be the most
      suitable biomarker for predicting NSCLC response to gamma-secretase inhibitors.
      gamma-Secretases have over 100 known gamma-secretase cleavage substrates. Many of
      the gamma-secretase substrates are directly involved in carcinogenesis or tumor
      progression, and are ideal candidates to be the "on-target" biomarkers for gamma
      secretase inhibitors. We propose the need to systematically test the gamma
      secretase and other targets as potential biomarkers for sensitivity before
      continuing clinical trials. Now that we have entered the postgenome/transcriptome
      era, this goal is easily attainable. Discovery of the biomarker(s) that predict
      sensitivity to gamma-secretase inhibitors would guide selection of the responder
      population that is most likely to benefit and move the compounds closer to
      approval for therapeutic use in NSCLC. Clin Cancer Res; 1-6. (c)2018 AACR.

PMID- 30104201
TI  - An unquestioned assumption in the debate on the dead donor rule.

PMID- 30104202
TI  - The maiming fields of Gaza.

PMID- 30104199
TI  - Microenvironmental regulation of cancer cell metabolism: implications for
      experimental design and translational studies.
AB  - Cancers have an altered metabolism, and there is interest in understanding
      precisely how oncogenic transformation alters cellular metabolism and how these
      metabolic alterations can translate into therapeutic opportunities. Researchers
      are developing increasingly powerful experimental techniques to study cellular
      metabolism, and these techniques have allowed for the analysis of cancer cell
      metabolism, both in tumors and in ex vivo cancer models. These analyses show
      that, while factors intrinsic to cancer cells such as oncogenic mutations, alter
      cellular metabolism, cell-extrinsic microenvironmental factors also substantially
      contribute to the metabolic phenotype of cancer cells. These findings highlight
      that microenvironmental factors within the tumor, such as nutrient availability,
      physical properties of the extracellular matrix, and interactions with stromal
      cells, can influence the metabolic phenotype of cancer cells and might ultimately
      dictate the response to metabolically targeted therapies. In an effort to better
      understand and target cancer metabolism, this Review focuses on the experimental
      evidence that microenvironmental factors regulate tumor metabolism, and on the
      implications of these findings for choosing appropriate model systems and
      experimental approaches.

PMID- 30104203
TI  - Budding yeast Rif1 binds to replication origins and protects DNA at blocked
      replication forks.
AB  - Despite its evolutionarily conserved function in controlling DNA replication, the
      chromosomal binding sites of the budding yeast Rif1 protein are not well
      understood. Here, we analyse genome-wide binding of budding yeast Rif1 by
      chromatin immunoprecipitation, during G1 phase and in S phase with replication
      progressing normally or blocked by hydroxyurea. Rif1 associates strongly with
      telomeres through interaction with Rap1. By comparing genomic binding of wild
      type Rif1 and truncated Rif1 lacking the Rap1-interaction domain, we identify
      hundreds of Rap1-dependent and Rap1-independent chromosome interaction sites.
      Rif1 binds to centromeres, highly transcribed genes and replication origins in a
      Rap1-independent manner, associating with both early and late-initiating origins.
      Interestingly, Rif1 also binds around activated origins when replication
      progression is blocked by hydroxyurea, suggesting association with blocked forks.
      Using nascent DNA labelling and DNA combing techniques, we find that in cells
      treated with hydroxyurea, yeast Rif1 stabilises recently synthesised DNA Our
      results indicate that, in addition to controlling DNA replication initiation,
      budding yeast Rif1 plays an ongoing role after initiation and controls events at
      blocked replication forks.

PMID- 30104204
TI  - DNA damage-induced replication stress results in PA200-proteasome-mediated
      degradation of acetylated histones.
AB  - Histone acetylation influences protein interactions and chromatin accessibility
      and plays an important role in the regulation of transcription, replication, and
      DNA repair. Conversely, DNA damage affects these crucial cellular processes and
      induces changes in histone acetylation. However, a comprehensive overview of the
      effects of DNA damage on the histone acetylation landscape is currently lacking.
      To quantify changes in histone acetylation, we developed an unbiased quantitative
      mass spectrometry analysis on affinity-purified acetylated histone peptides,
      generated by differential parallel proteolysis. We identify a large number of
      histone acetylation sites and observe an overall reduction of acetylated histone
      residues in response to DNA damage, indicative of a histone-wide loss of acetyl
      modifications. This decrease is mainly caused by DNA damage-induced replication
      stress coupled to specific proteasome-dependent loss of acetylated histones.
      Strikingly, this degradation of acetylated histones is independent of
      ubiquitylation but requires the PA200-proteasome activator, a complex that
      specifically targets acetylated histones for degradation. The uncovered
      replication stress-induced degradation of acetylated histones represents an
      important chromatin-modifying response to cope with replication stress.

PMID- 30104206
TI  - Characterizing the interaction between insulin-like growth factor 2 mRNA-binding
      protein 1 (IMP1) and KRAS expression.
AB  - Insulin-like growth factor 2 mRNA-binding protein-1 (IMP1) has high affinity for
      KRAS mRNA, and it can regulate KRAS expression in cells. We first characterized
      the molecular interaction between IMP1 and KRAS mRNA. Using IMP1 variants with a
      point mutation in the GXXG motif at each KH domain, we showed that all KH domains
      play a critical role in the binding of KRAS RNA. We mapped the IMP1-binding sites
      on KRAS mRNA and show that IMP1 has the highest affinity for nts 1-185. Although
      it has lower affinity, IMP1 does bind to other coding regions and the 3'-UTR of
      KRAS mRNA. Eight antisense oligonucleotides (AONs) were designed against KRAS RNA
      in the nts 1-185 region, but only two, SM6 and SM7, show potent inhibition of the
      IMP1-KRAS RNA interaction in vitro To test the activity of these two AONs in
      SW480 human colon cancer cells, we used 2'-O-methyl-modified versions of SM6 and
      SM7 in an attempt to down-regulate KRAS expression. To our surprise, both SM6 and
      SM7 had no effect on KRAS mRNA and protein expression, but significantly
      inhibited IMP1 protein expression without altering IMP1 mRNA level. On the other
      hand, knockdown of IMP1 using siRNA lowered the expression of KRAS. Using Renilla
      luciferase as a reporter, we found that IMP1 translation is significantly reduced
      in SM7-treated cells with no change in let-7a levels. The present study shows
      that the regulation of KRAS expression by IMP1 is complex and may involve both
      the IMP1 protein and its mRNA transcript.

PMID- 30104205
TI  - Inhibition of AIM2 inflammasome activation by a novel transcript isoform of
      IFI16.
AB  - Mouse p202 is a disease locus for lupus and a dominant-negative inhibitor of AIM2
      inflammasome activation. A human homolog of p202 has not been identified so far.
      Here, we report a novel transcript isoform of human IFI16-designated IFI16-beta,
      which has a domain architecture similar to that of mouse p202. Like p202, IFI16
      beta contains two HIN domains, but lacks the pyrin domain. IFI16-beta is
      ubiquitously expressed in various human tissues and cells. Its mRNA levels are
      also elevated in leukocytes of patients with lupus, virus-infected cells, and
      cells treated with interferon-beta or phorbol ester. IFI16-beta co-localizes with
      AIM2 in the cytoplasm, whereas IFI16-alpha is predominantly found in the nucleus.
      IFI16-beta interacts with AIM2 to impede the formation of a functional AIM2-ASC
      complex. In addition, IFI16-beta sequesters cytoplasmic dsDNA and renders it
      unavailable for AIM2 sensing. Enforced expression of IFI16-beta inhibits the
      activation of AIM2 inflammasome, whereas knockdown of IFI16-beta augments
      interleukin-1beta secretion triggered by dsDNA but not dsRNA Thus, cytoplasm
      localized IFI16-beta is functionally equivalent to mouse p202 that exerts an
      inhibitory effect on AIM2 inflammasome.

PMID- 30104208
TI  - A Novel LC System Embeds Analytes in Pre-formed Gradients for Rapid, Ultra-robust
      Proteomics.
AB  - To further integrate mass spectrometry (MS)-based proteomics into biomedical
      research and especially into clinical settings, high throughput and robustness
      are essential requirements. They are largely met in high-flow rate
      chromatographic systems for small molecules but these are not sufficiently
      sensitive for proteomics applications. Here we describe a new concept that
      delivers on these requirements while maintaining the sensitivity of current nano
      flow LC systems. Low-pressure pumps elute the sample from a disposable trap
      column, simultaneously forming a chromatographic gradient that is stored in a
      long storage loop. An auxiliary gradient creates an offset, ensuring the re
      focusing of the peptides before the separation on the analytical column by a
      single high-pressure pump. This simplified design enables robust operation over
      thousands of sample injections. Furthermore, the steps between injections are
      performed in parallel, reducing overhead time to a few minutes and allowing
      analysis of more than 200 samples per day. From fractionated HeLa cell lysates,
      deep proteomes covering more than 130,000 sequence unique peptides and close to
      10,000 proteins were rapidly acquired. Using this data as a library, we
      demonstrate quantitation of 5200 proteins in only 21 min. Thus, the new system -
      termed Evosep One - analyzes samples in an extremely robust and high throughput
      manner, without sacrificing in depth proteomics coverage.

PMID- 30104207
TI  - Analysis of RNA nearest neighbor parameters reveals interdependencies and
      quantifies the uncertainty in RNA secondary structure prediction.
AB  - RNA secondary structure prediction is often used to develop hypotheses about
      structure-function relationships for newly discovered RNA sequences, to identify
      unknown functional RNAs, and to design sequences. Secondary structure prediction
      methods typically use a thermodynamic model that estimates the free energy change
      of possible structures based on a set of nearest neighbor parameters. These
      parameters were derived from optical melting experiments of small model
      oligonucleotides. This work aims to better understand the precision of structure
      prediction. Here, the experimental errors in optical melting experiments were
      propagated to errors in the derived nearest neighbor parameter values and then to
      errors in RNA secondary structure prediction. To perform this analysis, the
      optical melting experimental values were systematically perturbed within the
      estimates of experimental error and alternative sets of nearest neighbor
      parameters were then derived from these error-bounded values. Secondary structure
      predictions using either the perturbed or reference parameter sets were then
      compared. This work demonstrated that the precision of RNA secondary structure
      prediction is more robust than suggested by previous work based on perturbation
      of the nearest neighbor parameters. This robustness is due to correlations
      between parameters. Additionally, this work identified weaknesses in the
      parameter derivation that makes accurate assessment of parameter uncertainty
      difficult. Considerations for experimental design are provided to mitigate these
      weaknesses are provided.

PMID- 30104210
TI  - Communication quality between the medical team and the head coach/manager is
      associated with injury burden and player availability in elite football clubs.
AB  - OBJECTIVES: We investigated medical staff interpretations and descriptions of
      internal communication quality in elite football teams to determine whether
      internal communication was correlated with injuries and/or player availability at
      training and matches. METHODS: Medical staff from 36 elite football clubs across
      17 European countries produced 77 reports at four postseason meetings to provide
      their perceptions of internal communications in their teams. They also recorded
      data on individual players' exposure to football and time-loss injuries. RESULTS:
      The injury burden and incidence of severe injuries were significantly higher in
      teams with low quality of communication between the head coach/manager and the
      medical team (scores of 1-2 on a 5-point Likert scale) compared with teams with
      moderate or high-quality scores (scores of 3-5; p=0.008 for both). Teams with low
      scores had 4%-5% lower training attendance (76% vs 83%, p=0.001) and less
      availability at matches (82% vs 88%, p=0.004) compared with teams with moderate
      or high communication quality scores. CONCLUSIONS: The quality of internal
      communication within a team was correlated with injury rates, training attendance
      and match availability.

PMID- 30104209
TI  - Isomeric Separation and Recognition of Anionic and Zwitterionic N-glycans from
      Royal Jelly Glycoproteins.
AB  - Royal jelly has received attention because of its necessity for the development
      of queen honeybees as well as claims of benefits on human health; this product of
      the hypopharyngeal glands of worker bees contains a large number of proteins,
      some of which have been claimed to have various biological effects only in their
      glycosylated state. However, although there have been glycomic and glycoproteomic
      analyses in the past, none of the glycan structures previously defined would
      appear to have potential to trigger specific biological functions. In the current
      study, whole royal jelly as well as single protein bands were subject to off-line
      LC-MALDI-TOF MS glycomic analyses, complemented by permethylation, Western
      blotting and arraying data. Similarly to recent in-depth studies on other insect
      species, previously overlooked glucuronic acid termini, sulfation of mannose
      residues and core beta-mannosylation of the N-glycans were found; additionally, a
      relatively rare zwitterionic modification with phosphoethanolamine is present, in
      contrast to the phosphorylcholine occurring in lepidopteran species. Indicative
      of tissue-specific remodelling of glycans in the Golgi apparatus of
      hypopharyngeal gland cells, only a low amount of fucosylated or paucimannosidic
      glycans were detected as compared with other insect samples or even bee venom.
      The unusual modifications of hybrid and multiantennary structures defined here
      may not only have a physiological role in honeybee development, but represent
      epitopes recognized by pentraxins with roles in animal innate immunity.

PMID- 30104211
TI  - The role of common gamma-chain cytokines in lung IL-22 regulation after acute
      exposure to Aspergillus fumigatus.
AB  - Humans are constantly exposed to the opportunistic mold Aspergillus fumigatus and
      disease caused by this pathogen is often determined by the magnitude of local and
      systemic immune responses. We have previously shown a protective role for IL-22
      after acute A. fumigatus exposure. Here, employing IL22CreR26ReYFP reporter mice,
      we identified iNKT cells, gammadelta T cells and ILC3 cells as lung cell sources
      of IL-22 in response to acute A. fumigatus exposure. As these cells often utilize
      common gamma-chain cytokines for their development or maintenance, we determined
      the role of IL-7, IL-21 and IL-15 on lung IL-22 induction and A. fumigatus lung
      clearance. We observed that IL-7, IL-21 and IL-15 were essential, partially
      required or negatively regulated the production of IL-22, respectively.
      Deficiency in IL-7 and IL-21, but not IL-15R, resulted in impaired fungal
      clearance. Surprisingly however, the absence of IL-7, IL-21 or IL-15R signaling
      had no effect on neutrophil recruitment. The levels of IL-1alpha, an essential
      anti-A. fumigatus proinflammatory cytokine, were increased in the absence of IL-7
      and IL-15R, but decreased in the absence of IL-21. IL-7 was responsible for
      maintaining lung iNKT cells and gammadelta T cells whereas IL-21 was responsible
      for maintaining lung iNKT cells and ILC3s. In contrast, IL-15R deficiency had no
      effect on the absolute numbers of any IL-22 cell source, rather resulting in
      enhanced per cell production of IL-22 by iNKT cells and gammadelta T cells.
      Collectively, these results provide insight into how the IL-22 response in the
      lung is shaped after acute A. fumigatus exposure.

PMID- 30104213
TI  - In Vivo Virulence Characterization of Pregnancy-Associated Listeria monocytogenes
      Infections.
AB  - Listeria monocytogenes is a foodborne pathogen that infects the placenta and can
      cause pregnancy complications. Listeriosis usually occurs as a sporadic
      infection, but large outbreaks are also reported. Virulence from clinical
      isolates is rarely analyzed due to the large number of animals required, but this
      knowledge could help guide the response to an outbreak. We implemented a DNA
      barcode system using signature tags that allowed us to efficiently assay
      variations in virulence across a large number of isolates. We tested 77 signature
      tagged clones of clinical L. monocytogenes strains from 72 infected human
      placentas and 5 immunocompromised patients, all of which were isolated since
      2000. These strains were tested for virulence in a modified competition assay in
      comparison to that of the laboratory strain 10403S. We used two in vivo models of
      listeriosis: the nonpregnant mouse and the pregnant guinea pig. Strains that were
      frequently found at a high abundance within infected organs were considered
      hypervirulent, while strains frequently found at a low abundance were considered
      hypovirulent. Virulence split relatively evenly among hypovirulent strains,
      hypervirulent strains, and strains as virulent as 10403S. The laboratory strain
      was found to have an intermediate virulence phenotype, supporting its suitability
      for use in pathogenesis studies. Further, we found that splenic virulence and
      placental virulence are closely linked in both the guinea pig and mouse models.
      This suggests that outbreak and sporadic pregnancy-associated L. monocytogenes
      strains are not generally more virulent than lab reference strains. However, some
      strains did show consistent and reproducible virulence differences, suggesting
      that their further study may reveal deeper insights into the biological
      underpinnings of listeriosis.

PMID- 30104212
TI  - Adjuvant Potential of Poly-alpha-l-Glutamine from the Cell Wall of Mycobacterium
      tuberculosis.
AB  - Novel adjuvants are in demand for improving the efficacy of human vaccines. The
      immunomodulatory properties of Mycobacterium tuberculosis cell wall components
      have been highlighted in the formulation of complete Freund's adjuvant (CFA). We
      have explored the adjuvant potential of poly-alpha-l-glutamine (PLG), a lesser
      known constituent of the pathogenic mycobacterial cell wall. Immune parameters
      indicated that the adjuvant potency of PLG was statistically comparable to that
      of CFA and better than that of alum in the context of H1 antigen (Ag85B and ESAT
      6 fusion). At 1 mg/dose, PLG augmented the immune response of Ag85B, BP26, and
      protective antigen (PA) by increasing serum antibodies and cytokines in the
      culture supernatant of antigen-stimulated splenocytes. PLG modulated the humoral
      response of vaccine candidate ESAT-6, eliciting significantly higher levels of
      total IgG and isotypes (IgG1, IgG2a, and IgG2b). Additionally, the splenocytes
      from PLG-adjuvanted mice displayed a robust increase in the Th1-specific gamma
      interferon, tumor necrosis factor alpha, interleukin-2 (IL-2), Th2-specific IL-6
      and IL-10, and Th17-specific IL-17A cytokines upon antigenic stimulation. PLG
      improved the protective efficacy of ESAT-6 by reducing bacillary load in the lung
      and spleen as well as granuloma formation, and it helped in maintaining vital
      health parameters of mice challenged with M. tuberculosis The median survival
      time of PLG-adjuvanted mice was 205 days, compared to 146 days for dimethyl
      dioctadecyl ammonium bromide-monophosphoryl lipid A (DDA-MPL)-vaccinated groups
      and 224 days for Mycobacterium bovis BCG-vaccinated groups. PLG enhanced the
      efficiency of the ESAT-6 vaccine to the level of BCG and better than that of DDA
      MPL (P < 0.05), with no ill effect in C57BL/6J mice. Our results propose that PLG
      is a promising adjuvant candidate for advanced experimentation.

PMID- 30104214
TI  - The Intracellular Cyclophilin PpiB Contributes to the Virulence of Staphylococcus
      aureus Independently of Its Peptidyl-Prolyl cis/trans Isomerase Activity.
AB  - The Staphylococcus aureus cyclophilin PpiB is an intracellular peptidyl prolyl
      cis/trans isomerase (PPIase) that has previously been shown to contribute to
      secreted nuclease and hemolytic activity. In this study, we investigated the
      contribution of PpiB to S. aureus virulence. Using a murine abscess model of
      infection, we demonstrated that a ppiB mutant is attenuated for virulence. We
      went on to investigate the mechanism through which PpiB protein contributes to
      virulence, in particular the contribution of PpiB PPIase activity. We determined
      the amino acid residues that are important for PpiB PPIase activity and showed
      that a single amino acid substitution (F64A) completely abrogates PPIase
      activity. Using purified PpiB F64A protein in vitro, we showed that PPIase
      activity only partially contributes to Nuc refolding and that PpiB also possesses
      PPIase-independent activity. Using allelic exchange, we introduced the F64A
      substitution onto the S. aureus chromosome, generating a strain that produces
      enzymatically inactive PpiB. Analysis of the PpiB F64A strain revealed that
      PPIase activity is not required for hemolysis of human blood or virulence in a
      mouse. Together, these results demonstrate that PpiB contributes to S. aureus
      virulence via a mechanism unrelated to prolyl isomerase activity.

PMID- 30104215
TI  - Host- and Helminth-Derived Endocannabinoids That Have Effects on Host Immunity
      Are Generated during Infection.
AB  - Helminths have coevolved with their hosts, resulting in the development of
      specialized host immune mechanisms and parasite-specific regulatory products.
      Identification of new pathways that regulate helminth infection could provide a
      better understanding of host-helminth interaction and may identify new
      therapeutic targets for helminth infection. Here we identify the endocannabinoid
      system as a new mechanism that influences host immunity to helminths.
      Endocannabinoids are lipid-derived signaling molecules that control important
      physiologic processes, such as feeding behavior and metabolism. Following murine
      infection with Nippostrongylus brasiliensis, an intestinal nematode with a life
      cycle similar to that of hookworms, we observed increased levels of
      endocannabinoids (2-arachidonoylglycerol [2-AG] or anandamide [AEA]) and the
      endocannabinoid-like molecule oleoylethanolamine (OEA) in infected lung and
      intestine. To investigate endocannabinoid function in helminth infection, we
      employed pharmacological inhibitors of cannabinoid subtype receptors 1 and 2
      (CB1R and CB2R). Compared to findings for vehicle-treated mice, inhibition of
      CB1R but not CB2R resulted in increased N. brasiliensis worm burden and egg
      output, associated with significantly decreased expression of the T helper type 2
      cytokine interleukin 5 (IL-5) in intestinal tissue and splenocyte cultures.
      Strikingly, bioinformatic analysis of genomic and transcriptome sequencing (RNA
      seq) data sets identified putative genes encoding endocannabinoid biosynthetic
      and degradative enzymes in many parasitic nematodes. To test the novel hypothesis
      that helminth parasites produce their own endocannabinoids, we measured
      endocannabinoid levels in N. brasiliensis by mass spectrometry and quantitative
      PCR and found that N. brasiliensis parasites produced endocannabinoids,
      especially at the infectious larval stage. To our knowledge, this is the first
      report of helminth- and host-derived endocannabinoids that promote host immune
      responses and reduce parasite burden.

PMID- 30104216
TI  - Glucan-chitin particles enhance Th17 response and improve protective efficacy of
      a multivalent antigen (rCpa1) against pulmonary Coccidioides posadasii infection.
AB  - Developing an effective and safe recombinant vaccine requires microbe-specific
      antigens combined with an adjuvant/delivery system to strengthen protective
      immunity. In this study, we designed and expressed a multivalent, recombinant
      Coccidioides polypeptide antigen (rCpa1) that consists of three previously
      identified antigens (i.e., Ag2/Pra, Cs-Ag and Pmp1) and 5 pathogen-derived
      peptides with high affinity for human MHC II molecules. The purified rCpa1 was
      encapsulated into four types of yeast cell-wall particles containing various
      compositions of beta-glucan, mannan and chitin or mixed with an oligonucleotide
      (ODN) containing 2 methylated dinucleotide CpG motifs. This multivalent antigen
      encapsulated into glucan-chitin particles (GCP-rCpa1) showed a significantly
      elevated reduction of fungal burden for human HLA-DR4 transgenic mice compared to
      the other tested adjuvant-rCpa1 formulations. Among the tested adjuvants GCPs and
      GPs were both capable of stimulating a mixed Th1 and Th17 response. Mice
      vaccinated with GCP-rCpa1 showed elevated IL-17 production in T-cell recall
      assays and early lung infiltration of activated Th1 and Th17 cells compared to GP
      rCpa1-vaccinated mice. Both C57BL/6 and HLA-DR4 transgenic mice that were
      vaccinated with GCP-rCpa1 vaccine increased surivial compared to the mice
      received GCPs alone. Concurringly, GCP-rCpa1 vaccine stimulated enhanced
      infiltration of macrophages to engulf and process the vaccine for antigen
      presentation in the injection sites compared to GP-rCpa1 injection. This is the
      first attempt to systematically characterize the presentation of a multivalent
      coccidioidomycosis vaccine encapsulated with selected adjuvants which enhance
      protective cellular immune response to infection.

PMID- 30104217
TI  - North American ATLL has a distinct mutational and transcriptional profile and
      responds to epigenetic therapies.
AB  - Adult T-cell leukemia lymphoma (ATLL) is a rare T cell neoplasm that is endemic
      in Japanese, Caribbean, and Latin American populations. Most North American ATLL
      patients are of Caribbean descent and are characterized by high rates of chemo
      refractory disease and worse prognosis compared with Japanese ATLL. To determine
      genomic differences between these 2 cohorts, we performed targeted exon
      sequencing on 30 North American ATLL patients and compared the results with the
      Japanese ATLL cases. Although the frequency of TP53 mutations was comparable, the
      mutation frequency in epigenetic and histone modifying genes (57%) was
      significantly higher, whereas the mutation frequency in JAK/STAT and T-cell
      receptor/NF-kappaB pathway genes was significantly lower. The most common type of
      epigenetic mutation is that affecting EP300 (20%). As a category, epigenetic
      mutations were associated with adverse prognosis. Dissimilarities with the
      Japanese cases were also revealed by RNA sequencing analysis of 9 primary patient
      samples. ATLL samples with a mutated EP300 gene have decreased total and acetyl
      p53 protein and a transcriptional signature reminiscent of p53-mutated cancers.
      Most importantly, decitabine has highly selective single-agent activity in the
      EP300-mutated ATLL samples, suggesting that decitabine treatment induces a
      synthetic lethal phenotype in EP300-mutated ATLL cells. In conclusion, we
      demonstrate that North American ATLL has a distinct genomic landscape that is
      characterized by frequent epigenetic mutations that are targetable preclinically
      with DNA methyltransferase inhibitors.

PMID- 30104219
TI  - Treatment dilemmas in asymptomatic children with primary hemophagocytic
      lymphohistiocytosis.
AB  - Asymptomatic carriers (ACs) of pathogenic biallelic mutations in causative genes
      for primary hemophagocytic lymphohistiocytosis (HLH) are at high risk of
      developing life-threatening HLH, which requires allogeneic hematopoietic stem
      cell transplantation (HSCT) to be cured. There are no guidelines on the
      management of these asymptomatic patients. We analyzed the outcomes of pairs of
      index cases (ICs) and subsequently diagnosed asymptomatic family members carrying
      the same genetic defect. We collected data from 22 HSCT centers worldwide. Sixty
      four children were evaluable. ICs presented with HLH at a median age of 16
      months. Seven of 32 ICs died during first-line therapy, and 2 are alive after
      chemotherapy only. In all, 23/32 underwent HSCT, and 16 of them are alive. At a
      median follow-up of 36 months from diagnosis, 18/32 ICs are alive. Median age of
      ACs at diagnosis was 5 months. Ten of 32 ACs activated HLH while being observed,
      and all underwent HSCT: 6/10 are alive and in complete remission (CR). 22/32 ACs
      remained asymptomatic, and 6/22 have received no treatment and are in CR at a
      median follow-up of 39 months. Sixteen of 22 underwent preemptive HSCT: 15/16 are
      alive and in CR. Eight-year probability of overall survival (pOS) in ACs who did
      not have activated HLH was significantly higher than that in ICs (95% vs 45%; P =
      .02), and pOS in ACs receiving HSCT before disease activation was significantly
      higher than in ACs receiving HSCT after HLH activation (93% vs 64%; P = .03).
      Preemptive HSCT in ACs proved to be safe and should be considered.

PMID- 30104221
TI  - What's happening in Neurology(r).

PMID- 30104223
TI  - What's happening in Neurology(r)Genetics.

PMID- 30104220
TI  - Acute hyperviscosity: syndromes and management.
AB  - Plasma hyperviscosity is a rare complication of both monoclonal and polyclonal
      disorders associated with elevation of immunoglobulins. Asymptomatic patients
      with an elevation in the serum viscosity do not require plasma exchange, and the
      majority will have other indications for therapeutic intervention. For patients
      with hemorrhagic or central nervous system manifestations, plasma exchange is the
      therapy of choice and is relatively safe. Viscosity measurements are not required
      to initiate therapy if the index of suspicion is high and the clinical
      presentation is typical. However, patients should have a sample sent for
      confirmation of the diagnosis. Whole-blood hyperviscosity is seen in patients
      with extreme elevation of the red cell and white cell count. Phlebotomy of
      patients with primary and secondary elevation of the red cell count is a well
      established therapy.

PMID- 30104222
TI  - What's happening in Neurology(r)Clinical Practice.

PMID- 30104218
TI  - Chronic immune response dysregulation in MDS pathogenesis.
AB  - Chronic innate immune signaling in hematopoietic cells is widely described in
      myelodysplastic syndromes (MDS), and innate immune pathway activation,
      predominantly via pattern recognition receptors, increases the risk of developing
      MDS. An inflammatory component to MDS has been reported for many years, but only
      recently has evidence supported a more direct role of chronic innate immune
      signaling and associated inflammatory pathways in the pathogenesis of MDS. Here
      we review recent findings and discuss relevant questions related to chronic
      immune response dysregulation in MDS.

PMID- 30104225
TI  - What's happening in Without Borders.

PMID- 30104224
TI  - What's happening in Neurology(r)Neuroimmunology & Neuroinflammation.

PMID- 30104226
TI  - The knit wit of Einstein.

PMID- 30104227
TI  - Fourth ventricle ependymoma mimicking benign paroxysmal positional vertigo.

PMID- 30104228
TI  - Pearls & Oy-sters: Bow hunter syndrome: A rare cause of posterior circulation
      stroke: Do not look the other way.

PMID- 30104229
TI  - Editors' note: The neurologic exam: Is it extinct?

PMID- 30104230
TI  - Reader response: The neurologic exam: Is it extinct?

PMID- 30104231
TI  - Reader response: The neurologic exam: Is it extinct?

PMID- 30104232
TI  - Reader response: The neurologic exam: Is it extinct?

PMID- 30104233
TI  - Vascular disease and cerebral amyloid deposition.

PMID- 30104234
TI  - Clinical Reasoning: A man with rapidly progressive weakness and respiratory
      failure.

PMID- 30104235
TI  - Teaching NeuroImages: Cerebral liposuction.

PMID- 30104236
TI  - Teaching Video NeuroImages: Marcus-Gunn pupil in tuberous sclerosis.

PMID- 30104239
TI  - "No respite" for NHS as heatwave exacerbates pressure on services.

PMID- 30104237
TI  - The Vibrio H-Ring Facilitates the Outer Membrane Penetration of the Polar
      Sheathed Flagellum.
AB  - The bacterial flagellum has evolved as one of the most remarkable nanomachines in
      nature. It provides swimming and swarming motilities that are often essential for
      the bacterial life cycle and pathogenesis. Many bacteria such as Salmonella and
      Vibrio species use flagella as an external propeller to move to favorable
      environments, whereas spirochetes utilize internal periplasmic flagella to drive
      a serpentine movement of the cell bodies through tissues. Here, we use cryo
      electron tomography to visualize the polar sheathed flagellum of Vibrio
      alginolyticus with particular focus on a Vibrio-specific feature, the H-ring. We
      characterized the H-ring by identifying its two components FlgT and FlgO. We
      found that the majority of flagella are located within the periplasmic space in
      the absence of the H-ring, which are different from those of external flagella in
      wild-type cells. Our results not only indicate the H-ring has a novel function in
      facilitating the penetration of the outer membrane and the assembly of the
      external sheathed flagella but also are consistent with the notion that the
      flagella have evolved to adapt highly diverse needs by receiving or removing
      accessary genes.IMPORTANCE Flagellum is the major organelle for motility in many
      bacterial species. While most bacteria possess external flagella, such as the
      multiple peritrichous flagella found in Escherichia coli and Salmonella enterica
      or the single polar sheathed flagellum in Vibrio spp., spirochetes uniquely
      assemble periplasmic flagella, which are embedded between their inner and outer
      membranes. Here, we show for the first time that the external flagella in Vibrio
      alginolyticus can be changed as periplasmic flagella by deleting two flagellar
      genes. The discovery here may provide new insights into the molecular basis
      underlying assembly, diversity, and evolution of flagella.

PMID- 30104238
TI  - Sycrp2 Is Essential for Twitching Motility in the Cyanobacterium Synechocystis
      sp. Strain PCC 6803.
AB  - Two cAMP receptor proteins (CRPs), Sycrp1 (encoded by sll1371) and Sycrp2
      (encoded by sll1924), exist in the cyanobacterium Synechocystis sp. strain PCC
      6803. Previous studies have demonstrated that Sycrp1 has binding affinity for
      cAMP and is involved in motility by regulating the formation of pili. However,
      the function of Sycrp2 remains unknown. Here, we report that sycrp2 disruption
      results in the loss of motility of Synechocystis sp. PCC 6803, and that the
      phenotype can be recovered by reintroducing the sycrp2 gene into the genome of
      sycrp2-disrupted mutants. Electron microscopy showed that the sycrp2-disrupted
      mutant lost the pilus apparatus on the cell surface, resulting in a lack of cell
      motility. Furthermore, the transcript level of the pilA9-pilA11 operon (essential
      for cell motility and regulated by the cAMP receptor protein Sycrp1) was markedly
      decreased in sycrp2-disrupted mutants compared with the wild-type strain.
      Moreover, yeast two-hybrid analysis and a pulldown assay demonstrated that Sycrp2
      interacted with Sycrp1 to form a heterodimer and that Sycrp1 and Sycrp2
      interacted with themselves to form homodimers. Gel mobility shift assays revealed
      that Sycrp1 specifically binds to the upstream region of pilA9 Together, these
      findings indicate that in Synechocystis sp. PCC 6803, Sycrp2 regulates the
      formation of pili and cell motility by interacting with Sycrp1.IMPORTANCE cAMP
      receptor proteins (CRPs) are widely distributed in cyanobacteria and play
      important roles in regulating gene expression. Although many cyanobacterial
      species have two cAMP receptor-like proteins, the functional links between them
      are unknown. Here, we found that Sycrp2 in the cyanobacterium Synechocystis sp.
      strain PCC 6803 is essential for twitching motility and that it interacts with
      Sycrp1, a known cAMP receptor protein involved with twitching motility. Our
      findings indicate that the two cAMP receptor-like proteins in cyanobacteria do
      not have functional redundancy but rather work together.

PMID- 30104240
TI  - Actin Cytoskeleton Remodeling Drives Breast Cancer Cell Escape from Natural
      Killer-Mediated Cytotoxicity.
AB  - Elucidation of the underlying molecular mechanisms of immune evasion in cancer is
      critical for the development of immunotherapies aimed to restore and stimulate
      effective antitumor immunity. Here, we evaluate the role of the actin
      cytoskeleton in breast cancer cell resistance to cytotoxic natural killer (NK)
      cells. A significant fraction of breast cancer cells responded to NK-cell attack
      via a surprisingly rapid and massive accumulation of F-actin near the immunologic
      synapse, a process we termed "actin response." Live-cell imaging provided direct
      evidence that the actin response is associated with tumor cell resistance to NK
      cell-mediated cell death. High-throughput imaging flow cytometry analyses showed
      that breast cancer cell lines highly resistant to NK cells were significantly
      enriched in actin response-competent cells as compared with susceptible cell
      lines. The actin response was not associated with a defect in NK-cell activation
      but correlated with reduced intracellular levels of the cytotoxic protease
      granzyme B and a lower rate of apoptosis in target cells. Inhibition of the actin
      response by knocking down CDC42 or N-WASP led to a significant increase in
      granzyme B levels in target cells and was sufficient to convert resistant breast
      cancer cell lines into a highly susceptible phenotype. The actin response and its
      protective effects were fully recapitulated using donor-derived primary NK cells
      as effector cells. Together, these findings establish the pivotal role of actin
      remodeling in breast cancer cell resistance to NK-cell-mediated
      killing.Significance: These findings establish the pivotal role of the actin
      cytoskeleton in driving breast cancer cell resistance to natural killer cells, a
      subset of cytotoxic lymphocytes with important roles in innate antitumor
      immunity. Cancer Res; 78(19); 5631-43. (c)2018 AACR.

PMID- 30104241
TI  - Paclitaxel Reduces Tumor Growth by Reprogramming Tumor-Associated Macrophages to
      an M1 Profile in a TLR4-Dependent Manner.
AB  - Paclitaxel is an antineoplastic agent widely used to treat several solid tumor
      types. The primary mechanism of action of paclitaxel is based on microtubule
      stabilization inducing cell-cycle arrest. Here, we use several tumor models to
      show that paclitaxel not only induces tumor cell-cycle arrest, but also promotes
      antitumor immunity. In vitro, paclitaxel reprogrammed M2-polarized macrophages to
      the M1-like phenotype in a TLR4-dependent manner, similarly to LPS. Paclitaxel
      also modulated the tumor-associated macrophage (TAM) profile in mouse models of
      breast and melanoma tumors; gene expression analysis showed that paclitaxel
      altered the M2-like signature of TAMs toward an M1-like profile. In mice
      selectively lacking TLR4 on myeloid cells, for example, macrophages (LysM-Cre+/
      /TLR4fl/fl), the antitumor effect of paclitaxel was attenuated. Gene expression
      analysis of tumor samples from patients with ovarian cancer before and after
      treatment with paclitaxel detected an enrichment of genes linked to the M1
      macrophage activation profile (IFNgamma-stimulated macrophages). These findings
      indicate that paclitaxel skews TAMs toward an immunocompetent profile via TLR4,
      which might contribute to the antitumor effect of paclitaxel and provide a
      rationale for new combination regimens comprising paclitaxel and immunotherapies
      as an anticancer treatment.Significance: This study provides new evidence that
      the antitumor effect of paclitaxel occurs in part via reactivation of the immune
      response against cancer, guiding tumor-associated macrophages toward the M1-like
      antitumor phenotype.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/20/5891/F1.large.jpg Cancer
      Res; 78(20); 5891-900. (c)2018 AACR See related commentary by Garassino et al.,
      p. 5729.

PMID- 30104243
TI  - SAMHD1 Posttranscriptionally Controls the Expression of Foxp3 and Helios in Human
      T Regulatory Cells.
AB  - Clinical application of Ag-specific T regulatory cells (Tregs) offers promise for
      the treatment of undesirable immune diseases. To achieve this goal, long-term
      expansion of Tregs is required to obtain sufficient numbers of cells. However,
      human Tregs are not stable ex vivo. Therefore, we previously developed an
      innovative Treg expansion protocol using 25mer-phosphorothioated random
      oligonucleotides (ODNps25). The addition of ODNps25 successfully resulted in the
      stabilization of engineered Ag-specific Tregs; however, the mechanism is not
      fully characterized. We first identified sterile alpha motif histidine-aspartate
      domain containing protein 1 (SAMHD1) as an ODNps25-binding protein using a UV
      cross-linking pull-down strategy. SAMHD1 physically interacted with the 3'
      untranslated region of Foxp3 mRNA and was translocated from nucleus to cytoplasm
      after ODNps25 treatment. Importantly, addition of ODNps25 enhanced the
      interaction of SAMHD1 and Foxp3 mRNA significantly, and this interaction was
      increased by TCR stimulation. Because ODNps25 binds to the nuclease (HD) domain
      of SAMHD1, we then established that overexpression of a dNTPase-deficient mutant
      (D137N) in Tregs significantly stabilized the expression level of the Foxp3
      protein. Furthermore, we found that TCR stimulation upregulates phosphorylation
      of the threonine residue (Thr592), which is a regulatory site to control SAMHD1
      activity, and phosphorylation of Thr592 is critical to control SAMHD1 activity to
      stabilize the expression of Foxp3 and Helios in Tregs. Taken together, we suggest
      that the interaction of ODNPs25 in HD or phosphorylation of Thr592 by TCR
      stimulation interferes with nuclease activity of SAMHD1, thereby stabilizing 3'
      untranslated region of Foxp3 and Helios mRNAs in long-term culture.

PMID- 30104242
TI  - Activation of Th1 Immunity within the Tumor Microenvironment Is Associated with
      Clinical Response to Lenalidomide in Chronic Lymphocytic Leukemia.
AB  - Immune stimulation contributes to lenalidomide's antitumor activity. Chronic
      lymphocytic leukemia (CLL) is characterized by the accumulation of mature,
      autoreactive B cells in secondary lymphoid tissues, blood, and bone marrow and
      progressive immune dysfunction. Previous studies in CLL indicated that
      lenalidomide can repair defective T cell function in vitro. Whether T cell
      activation is required for clinical response to lenalidomide remains unclear. In
      this study, we report changes in the immune microenvironment in patients with CLL
      treated with single-agent lenalidomide and associate the immunologic effects of
      lenalidomide with antitumor response. Within days of starting lenalidomide, T
      cells increased in the tumor microenvironment and showed Th1-type polarization.
      Gene expression profiling of pretreatment and on-treatment lymph node biopsy
      specimens revealed upregulation of IFN-gamma and many of its target genes in
      response to lenalidomide. The IFN-gamma-mediated Th1 response was limited to
      patients achieving a clinical response defined by a reduction in lymphadenopathy.
      Deep sequencing of TCR genes revealed decreasing diversity of the T cell
      repertoire and an expansion of select clonotypes in responders. To validate our
      observations, we stimulated T cells and CLL cells with lenalidomide in culture
      and detected lenalidomide-dependent increases in T cell proliferation. Taken
      together, our data demonstrate that lenalidomide induced Th1 immunity in the
      lymph node that is associated with clinical response.

PMID- 30104244
TI  - Impaired Development and Expansion of Germinal Center Follicular Th Cells in
      Simian Immunodeficiency Virus-Infected Neonatal Macaques.
AB  - Germinal center (GC) CD4+ follicular Th (Tfh) cells are critical for cognate B
      cell help in humoral immune responses to pathogenic infections. Although Tfh
      cells are expanded or depleted in HIV/SIV-infected adults, the effects of
      pediatric HIV/SIV infection on Tfh cells remain unclear. In this study, we
      examined changes in lymphoid follicle formation in lymph nodes focusing on GC Tfh
      cells, B cell development, and differentiation in SIV-infected neonatal rhesus
      macaques (Macaca mulatta) compared with age-matched cohorts. Our data showed that
      follicles and GCs of normal infants rapidly formed in the first few weeks of age,
      in parallel with increasing GC Tfh cells in various lymphoid tissues. In
      contrast, GC development and GC Tfh cells were markedly impaired in SIV-infected
      infants. There was a very low frequency of GC Tfh cells throughout SIV infection
      in neonates and subsequent infants, accompanied by high viremia, reduction of B
      cell proliferation/resting memory B cells, and displayed proinflammatory
      unresponsiveness. These findings indicate neonatal HIV/SIV infection compromises
      the development of GC Tfh cells, likely contributing to ineffective Ab responses,
      high viremia, and eventually rapid disease progression to AIDS.

PMID- 30104246
TI  - Glucagon-Like Peptide 1 and Its Cleavage Products Are Renoprotective in Murine
      Diabetic Nephropathy.
AB  - Incretin-based therapies, including glucagon-like peptide 1 (GLP-1) receptor
      agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors, are potent glucose
      lowering drugs. Still, only GLP-1 receptor agonists with close peptide homology
      to GLP-1 (liraglutide and semaglutide) but neither exenatide-based GLP-1 receptor
      agonists nor DPP-4 inhibitors were found to reduce cardiovascular events. This
      different response might relate to GLP-1 receptor-independent actions of GLP-1
      caused by cleavage products only liberated by GLP-1 receptor agonists with close
      peptide structure to GLP-1. To test this hypothesis, we directly compared
      metabolic, renal, and cardiac effects of GLP-1 and its cleavage products in
      diabetic db/db mice. Using an adeno-associated viral vector system, we
      overexpressed DPP-4-resistant GLP-1 (7-37 Mut8) and the two GLP-1 cleavage
      products, GLP-1 (9-37) and GLP-1 (28-37), in diabetic db/db mice. Only GLP-1 (7
      37 Mut8), but none of the cleavage products, significantly improved glucose
      metabolism. Still, all GLP-1 constructs significantly reduced tubulointerstitial
      renal damage, lowered expression of the tubular injury markers, and attenuated
      renal accumulation of macrophages and T cells. This was associated with a
      systemic immunomodulatory effect, which was similarly found in an acute renal
      ischemia/reperfusion injury model. In conclusion, GLP-1 cleavage products proved
      sufficient to mediate organ-protective effects, which might help to explain
      differences between GLP-1 receptor agonists.

PMID- 30104245
TI  - Engineering a Single-Agent Cytokine/Antibody Fusion That Selectively Expands
      Regulatory T Cells for Autoimmune Disease Therapy.
AB  - IL-2 has been used to treat diseases ranging from cancer to autoimmune disorders,
      but its concurrent immunostimulatory and immunosuppressive effects hinder
      efficacy. IL-2 orchestrates immune cell function through activation of a high
      affinity heterotrimeric receptor (composed of IL-2Ralpha, IL-2Rbeta, and common
      gamma [gammac]). IL-2Ralpha, which is highly expressed on regulatory T (TReg)
      cells, regulates IL-2 sensitivity. Previous studies have shown that complexation
      of IL-2 with the JES6-1 Ab preferentially biases cytokine activity toward TReg
      cells through a unique mechanism whereby IL-2 is exchanged from the Ab to IL
      2Ralpha. However, clinical adoption of a mixed Ab/cytokine complex regimen is
      limited by stoichiometry and stability concerns. In this study, through structure
      guided design, we engineered a single agent fusion of the IL-2 cytokine and JES6
      1 Ab that, despite being covalently linked, preserves IL-2 exchange, selectively
      stimulating TReg expansion and exhibiting superior disease control to the mixed
      IL-2/JES6-1 complex in a mouse colitis model. These studies provide an
      engineering blueprint for resolving a major barrier to the implementation of
      functionally similar IL-2/Ab complexes for treatment of human disease.

PMID- 30104247
TI  - SF1-Specific AMPKalpha1 Deletion Protects Against Diet-Induced Obesity.
AB  - AMPK is a cellular gauge that is activated under conditions of low energy,
      increasing energy production and reducing energy waste. Current evidence links
      hypothalamic AMPK with the central regulation of energy balance. However, it is
      unclear whether targeting hypothalamic AMPK has beneficial effects in obesity.
      Here, we show that genetic inhibition of AMPK in the ventromedial nucleus of the
      hypothalamus (VMH) protects against high-fat diet (HFD)-induced obesity by
      increasing brown adipose tissue (BAT) thermogenesis and subsequently energy
      expenditure. Notably, this effect depends upon the AMPKalpha1 isoform in
      steroidogenic factor 1 (SF1) neurons of the VMH, since mice bearing selective
      ablation of AMPKalpha1 in SF1 neurons display resistance to diet-induced obesity,
      increased BAT thermogenesis, browning of white adipose tissue, and improved
      glucose and lipid homeostasis. Overall, our findings point to hypothalamic AMPK
      in specific neuronal populations as a potential druggable target for the
      treatment of obesity and associated metabolic disorders.

PMID- 30104248
TI  - Extending Remission and Reversing New-Onset Type 1 Diabetes by Targeted Ablation
      of Autoreactive T Cells.
AB  - Preserving endogenous insulin production is clinically advantageous and remains a
      vital unmet challenge in the treatment and reversal of type 1 diabetes. Although
      broad immunosuppression has had limited success in prolonging the so-called
      remission period, it comes at the cost of compromising beneficial immunity. Here,
      we used a novel strategy to specifically deplete the activated diabetogenic T
      cells that drive pathogenesis while preserving not only endogenous insulin
      production but also protective immunity. Effector T (Teff) cells, such as
      diabetogenic T cells, are naturally poised on the edge of apoptosis because of
      activation-induced DNA damage that stresses the p53 regulation of the cell cycle.
      We have found that using small molecular inhibitors that further potentiate p53
      while inhibiting the G2/M cell cycle checkpoint control drives apoptosis of
      activated T cells in vivo. When delivered at the onset of disease, these
      inhibitors significantly reduce diabetogenic Teff cells, prolong remission,
      preserve functional islets, and protect islet allografts while leaving naive,
      memory, and regulatory T-cell populations functionally untouched. Thus, the
      targeted manipulation of p53 and cell cycle checkpoints represents a new
      therapeutic modality for the preservation of islet beta-cells in new-onset type 1
      diabetes or after islet transplant.

PMID- 30104250
TI  - Growth Differentiation Factor 15 Maturation Requires Proteolytic Cleavage by
      PCSK3, -5, and -6.
AB  - Growth differentiation factor 15 (GDF15) is a secreted protein with pleotropic
      functions from the transforming growth factor beta (TGF-beta) family. GDF15 is
      synthesized as a precursor and undergoes proteolytic cleavage to generate mature
      GDF15. The strong appetite-suppressing effect of mature GDF15 makes it an
      attractive therapeutic agent/target for diseases such as obesity and cachexia. In
      addition, clinical studies indicate that circulating, mature GDF15 is an
      independent biomarker for heart failure. We recently found that GDF15 functions
      as a heart-derived hormone that inhibits liver growth hormone signaling and
      postnatal body growth in the pediatric period. However, little is known about the
      mechanism of GDF15 maturation, in particular the enzymes that mediate GDF15
      precursor cleavage. We investigated which candidate proteases can cleave GDF15
      precursor and generate mature GDF15 in cardiomyocytes in vitro and mouse hearts
      in vivo We discovered that three members of the proprotein convertase,
      subtilisin/kexin-type (PCSK) family, namely, PCSK3, PCSK5, and PCSK6, can
      efficiently cleave GDF15 precursor, therefore licensing its maturation both in
      vitro and in vivo Our studies suggest that PCSK3, -5, and -6 mediate a crucial
      step of GDF15 maturation through proteolytic cleavage of the precursor. These
      results also reveal new targets for therapeutic application of GDF15 in treating
      obesity and cachexia.

PMID- 30104251
TI  - Decreased c-Myc mRNA Stability via the MicroRNA 141-3p/AUF1 Axis Is Crucial for
      p63alpha Inhibition of Cyclin D1 Gene Transcription and Bladder Cancer Cell
      Tumorigenicity.
AB  - Bladder cancer (BC) ranks as the sixth most common cancer in the United States
      and is the leading cause of death in patients with urinary malignancies. p63 is a
      member of the p53 family and is believed to function as a tumor suppressor in
      human BCs. Our most recent studies revealed a previously unknown function of the
      RING of XIAP in promoting microRNA 4295 (miR-4295) transcription, thereby
      reducing p63alpha protein translation and enhancing normal urothelial
      transformation, whereas p63alpha upregulates hsp70 transcription, subsequently
      activating the HSP70/Wasf3/Wave3/matrix metalloproteinase 9 (MMP-9) axis and
      promoting BC cell invasion via initiating the transcription factor E2F1. In this
      study, we found that p63alpha inhibited cyclin D1 protein expression,
      subsequently decreasing the ability of BC cell anchorage-independent growth in
      vitro and tumorigenicity in vivo Mechanistic studies demonstrated that p63alpha
      expression is able to downregulate cyclin D1 gene transcription through
      attenuation of c-Myc mRNA stability. We further show that the reduction of miR
      141-3p expression by p63alpha directly releases its inhibition of 3' untranslated
      region (UTR) activity of AU-rich element RNA-binding factor 1 (AUF1) mRNA,
      thereby increasing AUF1 protein translation and further resulting in degradation
      of c-Myc mRNA, which, in turn, reduces cyclin D1 gene transcription and BC cell
      anchorage-independent growth. Collectively, our results demonstrate that p63alpha
      is a negative regulator of BC cell tumorigenic growth, a distinctly different
      function than its promotion of BC invasion, thus providing further new insight
      into the "two faces" of p63alpha in regulation of BC cell tumorigenic growth and
      progression/invasion.

PMID- 30104252
TI  - CD19 alterations emerging after CD19-directed immunotherapy cause retention of
      the misfolded protein in the endoplasmic reticulum.
AB  - We have previously described a mechanism of acquired resistance of B-cell acute
      lymphoblastic leukemia to CD19-directed chimeric antigen receptor T-cell (CART)
      immunotherapy. It was based on in-frame insertions in or skipping of CD19 exon 2.
      To distinguish between epitope loss and defects in surface localization, we used
      retroviral transduction and genome editing to generate cell lines expressing CD19
      exon 2 variants (CD19ex2vs) bearing VSV-G tags. These lines were negative by live
      cell flow cytometry with an anti-VSV-G antibody and resistant to killing by VSV-G
      directed antibody-drug conjugates (ADC), suggestive of a defect in surface
      localization. Indeed, pulse-chase and alpha-mannosidase inhibitor assays showed
      that all CD19ex2vs acquired ER-specific high mannose-type sugars, but not complex
      type glycans synthesized in Golgi. When fused with GFP, CD19ex2vs (including a
      mutant lacking the relevant disulfide bond) showed colocalization with ER
      markers, implicating protein misfolding. Mass spectrometric profiling of CD19
      interacting proteins demonstrated that CD19ex2vs fail to bind to the key
      tetraspanin CD81 and instead interact with ER-resident chaperones such as
      calnexin and ER transporters involved in antigen presentation. Thus, even the
      intact domains of CD19ex2vs cannot be easily targeted with ADCs or current CD19
      CARTs but could serve as sources of peptides for MHC-restricted presentation and
      TCR-mediated killing.

PMID- 30104253
TI  - E2F1 Mediates the Retinoic Acid-Induced Transcription of Tshz1 during Neuronal
      Differentiation in a Cell Division-Dependent Manner.
AB  - The involvement of cell division in cellular differentiation has long been
      accepted. Cell division may be required not only for the expansion of a
      differentiated cell population but also for the execution of differentiation
      processes. Nonetheless, knowledge regarding how specific differentiation
      processes are controlled in a cell division-dependent manner is far from
      complete. Here, we determined the involvement of cell division in neuronal
      differentiation. We initially confirmed that cell division is an essential event
      for the neuronal differentiation of P19 embryonic carcinoma cells. We
      investigated the induction mechanisms of Tshz1, whose expression is induced by
      retinoic acid (RA) in a cell division-dependent manner. Promoter analysis of
      Tshz1 revealed a specific region required for RA-dependent transcription. A
      series of experiments was used to identify E2F1 as the induction factor for the
      RA-dependent transcription of Tshz1 We propose that E2F1 mediates neuronal
      differentiation in a cell division-dependent manner.

PMID- 30104255
TI  - Estimating Mesophyll Conductance from Measurements of C18OO Photosynthetic
      Discrimination and Carbonic Anhydrase Activity.
AB  - Carbonic anhydrase (CA) activity in leaves catalyzes the 18O exchange between CO2
      and water during photosynthesis. This feature has been used to estimate the
      mesophyll conductance to CO2 (g m) from measurements of online C18OO
      photosynthetic discrimination (?18O). Based on CA assays on leaf extracts, it has
      been argued that CO2 in mesophyll cells should be in isotopic equilibrium with
      water in most C3 species as well as many C4 dicot species. However, this seems
      incompatible with ?18O data that would indicate a much lower degree of
      equilibration, especially in C4 plants under high light intensity. This apparent
      contradiction is resolved here using a new model of C3 and C4 photosynthetic
      discrimination that includes competition between CO2 hydration and carboxylation
      and the contribution of respiratory fluxes. This new modeling framework is used
      to revisit previously published data sets on C3 and C4 species, including CA
      deficient plants. We conclude that (1) newly ?18O-derived g m values are usually
      close but significantly higher (typically 20% and up to 50%) than those derived
      assuming full equilibration and (2) despite the uncertainty associated with the
      respiration rate in light, or the water isotope gradient between mesophyll and
      bundle sheath cells, robust estimates of ?18O-derived g m can be achieved in both
      C3 and C4 plants.

PMID- 30104254
TI  - Red Light-Induced Phosphorylation of Plasma Membrane H+-ATPase in Stomatal Guard
      Cells.
AB  - Stomatal opening is stimulated by red and blue light. Blue light activates plasma
      membrane (PM) H+-ATPase by phosphorylating its penultimate residue, threonine,
      via a blue light photoreceptor phototropin-mediated signaling pathway in guard
      cells. Blue light-activated PM H+-ATPase promotes the accumulation of osmolytes
      and, thus, the osmotic influx of water into guard cells, driving stomatal
      opening. Red light-induced stomatal opening is thought to be dependent on
      photosynthesis in both guard cell chloroplasts and mesophyll cells; however, how
      red light induces stomatal opening and whether PM H+-ATPase is involved in this
      process have remained unclear. In this study, we established an
      immunohistochemical technique to detect the phosphorylation level of PM H+-ATPase
      in guard cells using whole leaves of Arabidopsis (Arabidopsis thaliana) and
      unexpectedly found that red light induces PM H+-ATPase phosphorylation in whole
      leaves. Red light-induced PM H+-ATPase phosphorylation in whole leaves was
      correlated with stomatal opening under red light and was inhibited by the plant
      hormone abscisic acid. In aha1-9, a knockout mutant of one of the major isoforms
      of PM H+-ATPase in guard cells, red light-dependent stomatal opening was delayed
      in whole leaves. Furthermore, the photosynthetic electron transport inhibitor 3
      (3,4-dichlorophenyl)-1,1-dimethylurea inhibited red light-induced PM H+-ATPase
      phosphorylation as well as red light-induced stomatal opening in whole leaves.
      Our results indicate that red light-induced PM H+-ATPase phosphorylation in guard
      cells promotes stomatal opening in whole leaves, providing insight into the
      photosynthetic regulation of stomatal opening.

PMID- 30104257
TI  - Italy suspends mandatory vaccination of nursery children after Senate vote.

PMID- 30104249
TI  - Reduction in White Blood Cell, Neutrophil, and Red Blood Cell Counts Related to
      Sex, HLA, and Islet Autoantibodies in Swedish TEDDY Children at Increased Risk
      for Type 1 Diabetes.
AB  - Islet autoantibodies (IAs) precede the clinical onset of type 1 diabetes (T1D);
      however, the knowledge is limited about whether the prodrome affects complete
      blood counts (CBCs) in 4- to 12-year-old children with increased genetic risk for
      T1D. This study tested whether CBCs were altered in 4- to 12-year-old children
      without (n = 376) or with one or several IAs against insulin, GAD65, or IA-2 (n =
      72). CBC was analyzed during longitudinal follow-up in 448 Swedish children
      enrolled in The Environmental Determinants of Diabetes in the Young (TEDDY)
      study. A linear mixed-effects model was used to assess potential association
      between IA and CBC measurements over time. The white blood cell and neutrophil
      counts were reduced in children with IAs, primarily in boys. In contrast, girls
      had lower levels of hemoglobin and hematocrit. Positivity for multiple IAs showed
      the lowest counts in white blood cells and neutrophils in boys and red blood
      cells, hemoglobin, and hematocrit in girls. These associations were primarily
      observed in children with the HLA-DR3-DQ2/DR4-DQ8 genotype. We conclude that the
      reduction in neutrophils and red blood cells in children with multiple IAs and
      HLA-DR3-DQ2/DR4-DQ8 genotype may signal a sex-dependent islet autoimmunity
      detected in longitudinal CBCs.

PMID- 30104256
TI  - Sulfate Metabolism in C4 Flaveria Species Is Controlled by the Root and Connected
      to Serine Biosynthesis.
AB  - The evolution of C4 photosynthesis led to an increase in carbon assimilation
      rates and plant growth compared to C3 photosynthetic plants. This enhanced plant
      growth, in turn, affects the requirement for soil-derived mineral nutrients.
      However, mineral plant nutrition has scarcely been considered in connection with
      C4 photosynthesis. Sulfur is crucial for plant growth and development, and
      preliminary studies in the genus Flaveria suggested metabolic differences in
      sulfate assimilation along the C4 evolutionary trajectory. Here, we show that in
      controlled conditions, foliar accumulation of the reduced sulfur compounds Cys
      and glutathione (GSH) increased with progressing establishment of the C4
      photosynthetic cycle in different Flaveria species. An enhanced demand for
      reduced sulfur in C4 Flaveria species is reflected in high rates of [35S]sulfate
      incorporation into GSH upon sulfate deprivation and increased GSH turnover as a
      reaction to the inhibition of GSH synthesis. Expression analyses indicate that
      the gamma-glutamyl cycle is crucial for the recycling of GSH in C4 species.
      Sulfate reduction and GSH synthesis seems to be preferentially localized in the
      roots of C4 species, which might be linked to its colocalization with the
      phosphorylated pathway of Ser biosynthesis. Interspecies grafting experiments of
      F. robusta (C3) and F. bidentis (C4) revealed that the root system primarily
      controls sulfate acquisition, GSH synthesis, and sulfate and metabolite
      allocation in C3 and C4 plants. This study thus shows that evolution of C4
      photosynthesis resulted in a wide range of adaptations of sulfur metabolism and
      points out the need for broader studies on importance of mineral nutrition for C4
      plants.

PMID- 30104258
TI  - Dynamic stability of the actin ecosystem.
AB  - In cells, actin filaments continuously assemble and disassemble while maintaining
      an apparently constant network structure. This suggests a perfect balance between
      dynamic processes. Such behavior, operating far out of equilibrium by the
      hydrolysis of ATP, is called a dynamic steady state. This dynamic steady state
      confers a high degree of plasticity to cytoskeleton networks that allows them to
      adapt and optimize their architecture in response to external changes on short
      time-scales, thus permitting cells to adjust to their environment. In this
      Review, we summarize what is known about the cellular actin steady state, and
      what gaps remain in our understanding of this fundamental dynamic process that
      balances the different forms of actin organization in a cell. We focus on the
      minimal steps to achieve a steady state, discuss the potential feedback
      mechanisms at play to balance this steady state and conclude with an outlook on
      what is needed to fully understand its molecular nature.

PMID- 30104260
TI  - Validation of the entrustable professional activities for new pharmacy graduates.
AB  - PURPOSE: The face validity of the core entrustable professional activities (EPAs)
      for new pharmacy graduates published by the American Association of Colleges of
      Pharmacy (AACP) in 2017 was evaluated. METHODS: A 28-item questionnaire was sent
      to experienced pharmacy practitioners affiliated with 4 schools of pharmacy. In
      addition to demographic information about education, training, credentials, and
      practice setting, participants were asked whether each EPA statement was
      pertinent to pharmacy practice and an expected activity that all pharmacists
      should be able to perform. Questions regarding the secondary attributes of the
      EPA statements examined whether each activity is observable, is measurable, is
      transferable to multiple practice settings, and integrates multiple competencies.
      RESULTS: The questionnaire was distributed to 137 eligible participants, and 71
      usable survey responses were received. Participants consistently agreed (>=75%
      agreement) that the 15 EPA statements for new pharmacy graduates describe
      activities that are pertinent to pharmacy practice and that pharmacists are
      expected to perform. A consistent level of agreement was observed regardless of
      the preceptor's employment with a college or school, board certification status,
      or completion of postgraduate training, and no statistical differences in level
      of agreement were found based on these attributes. There was consistent agreement
      (>=60%) across geographic regions. No statistical differences in agreement were
      found between acute care practitioners and ambulatory care practitioners.
      CONCLUSION: A survey suggested that the core EPAs developed and vetted by AACP
      have face validity and are believed by experienced pharmacy preceptor
      practitioners to be pertinent to pharmacy practice and to describe activities
      that all pharmacists should be able to competently perform.

PMID- 30104259
TI  - Development and economic evaluation of a pharmacist-provided chronic care
      management service in an ambulatory care geriatrics clinic.
AB  - PURPOSE: The implementation and delivery of a pharmacist-led chronic care
      management (CCM) service in a geriatric primary care clinic are described.
      METHODS: A CCM service was provided March 1 through December 31, 2016, at the
      University of Colorado Hospital Seniors Clinic ("Seniors Clinic"). The electronic
      health record (EHR) team for the University of Colorado Health system developed a
      patient registry through EPIC Healthy Planet (Epic Systems Corp., Verona, WI) to
      identify patients at the Seniors Clinic eligible for CCM services. The EHR team
      constructed a note type and documentation template within the EHR to ensure
      documentation of all necessary components for billing and to allow individual
      clinical staff to document the time spent providing CCM care. RESULTS: Overall,
      36 elderly patients enrolled in the pharmacist-provided CCM service over the 10
      months. Clinical pharmacists spent a total of 156-849 minutes per month providing
      CCM services, with a mean outreach time of 45.4 minutes per patient. The clinical
      pharmacists submitted 95 claims, and all but 5 were paid. The total amount
      reimbursed from the health plans during the 10 months was $2,775.02. CONCLUSION:
      Medicare patients were successfully enrolled in a CCM service in a geriatrics
      primary care clinic led by clinical pharmacists and medical providers. The CCM
      services were more time-consuming than the allotted 20 minutes per patient per
      month with the CCM Current Procedural Terminology code used during this study.

PMID- 30104262
TI  - Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar
      macrophages.
AB  - OBJECTIVE: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL).
      We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on
      alveolar macrophage (AM) function. METHODS: AMs were treated with ECVC and
      nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine,
      chemokine and protease release, reactive oxygen species (ROS) release and
      bacterial phagocytosis were assessed. RESULTS: Macrophage culture with ECL or
      ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic
      at lower concentrations than ECL and resulted in increased apoptosis and
      necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to
      a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and
      significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide
      3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage
      viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor
      alpha, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9
      was significantly increased following ECVC challenge. Treatment with the anti
      oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC
      to levels not significantly different from baseline and restored phagocytic
      function. CONCLUSIONS: ECVC is significantly more toxic to AMs than non-vaped
      ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced
      by e-cigarette vapour may induce an inflammatory state in AMs within the lung
      that is partly dependent on nicotine. Inhibition of phagocytosis also suggests
      users may suffer from impaired bacterial clearance. While further research is
      needed to fully understand the effects of e-cigarette exposure in humans in vivo,
      we caution against the widely held opinion that e-cigarettes are safe.

PMID- 30104261
TI  - Estimating Genetic Relatedness in Admixed Populations.
AB  - Estimating genetic relatedness, and inbreeding coefficients is important to the
      fields of quantitative genetics, conservation, genome-wide association studies
      (GWAS), and population genetics. Traditional estimators of genetic relatedness
      assume an underlying model of population structure. Each individual is assigned
      to a population, depending on a priori assumptions about geographical location of
      sampling, proximity, or genetic similarity. But often, this population assignment
      is unknown and assumptions about assignment can lead to erroneous estimates of
      genetic relatedness. I develop a generalized method of estimating relatedness in
      admixed populations, to account for (1) multi-allelic genomic data, (2) including
      all nine Identity By Descent (IBD) states, and implement a maximum likelihood
      based estimator of pairwise genetic relatedness in structured populations, part
      of the software, InRelate. Replicated estimations of genetic relatedness between
      admixed full sib (FS), half sib (HS), first cousin (FC), parent-offspring (PO)
      and unrelated (UR) dyads in simulated and empirical data from the HGDP-CEPH panel
      show considerably low bias and error while using InRelate, compared to several
      previously developed methods. I also propose a bootstrap scheme, and a series of
      Wald Tests to assign relatedness categories to pairs of individuals.

PMID- 30104263
TI  - Giant variant of acquired reactive perforating collagenosis in diabetic
      nephropathy.

PMID- 30104264
TI  - APX001A In Vitro Activity against Contemporary Blood Isolates and Candida auris
      Determined by the EUCAST Reference Method.
AB  - APX001A is the active moiety of the first-in-class drug candidate APX001. So far,
      most susceptibility testing studies have examined <=30 isolates/species, and only
      one used the EUCAST method. Here, we investigated the in vitro activity of
      APX001A and five comparators against 540 candidemia and 122 C. auris isolates.
      Isolates (17 Candida and 3 yeast species) were identified using CHROMagar, matrix
      assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF)
      and, when needed, internal transcribed space (ITS) sequencing. EUCAST E.Def 7.3.1
      susceptibility testing included APX001A, amphotericin B, anidulafungin,
      micafungin, fluconazole, and voriconazole. Wild-type upper limits (WT-UL) were
      established following the EUCAST principles for epidemiological cutoff value
      setting for APX001A, allowing classification as wild type (WT) or non-WT. APX001A
      MIC50 values (mg/liter) were as follows: Candida albicans, Candida dubliniensis,
      and Candida tropicalis, 0.004 to 0.008; Candida parapsilosis and Candida auris,
      0.016; Candida glabrata, 0.06; and Candida krusei, >0.5. APX001A MICs against the
      rare species varied from <=0.0005 (C. pelliculosa) to >0.5 (Candida norvegensis).
      APX001A was equally or more active in vitro than the comparators against all
      species except C. krusei and C. norvegensis Four isolates were APX001A non-WT;
      all were fluconazole resistant. A correlation was observed between APX001A and
      fluconazole MICs across all species except Candida guilliermondii and C. auris,
      and when comparing high and low fluconazole MIC isolates of C. albicans, C.
      dubliniensis, C. glabrata, C. tropicalis, and C. auris APX001A showed promising
      in vitro activity against most Candida and other yeast species, including C.
      auris, compared to five comparators. WT-UL were suggested for the common species,
      and a new and unexplained correlation to fluconazole susceptibility was observed.

PMID- 30104265
TI  - Nontuberculous Mycobacterial Lung Diseases Caused by Mixed Infection with
      Mycobacterium avium Complex and Mycobacterium abscessus Complex.
AB  - Mycobacterium avium complex (MAC) and M. abscessus complex (MABC) comprise the
      two most important human pathogen groups causing nontuberculous mycobacterial
      lung disease (NTM-LD). However, there are limited data regarding NTM-LD caused by
      mixed NTM infections. This study aimed to evaluate the clinical characteristics
      and treatment outcomes in patients with NTM-LD caused by mixed infection with
      these two major NTM pathogen groups. Seventy-one consecutive patients who had
      been diagnosed with NTM-LD caused by mixed infection with MAC (M. avium or M.
      intracellulare) and MABC (M. abscessus or M. massiliense) between January 2010
      and December 2015 were identified. Nearly all patients (96%) had the nodular
      bronchiectatic form of NTM-LD. Mixed infection with MAC and M. massiliense (n =
      47, 66%) was more common than mixed infection with MAC and M. abscessus (n = 24,
      34%), and among the 43 (61%) patients who were treated for NTM-LD for more than
      12 months, sputum culture conversion rates were significantly lower in patients
      infected with MAC and M. abscessus (25% [3/12]) than in patients infected with
      MAC and M. massiliense (61% [19/31, P = 0.033]). Additionally, M. massiliense and
      M. abscessus showed marked differences in clarithromycin susceptibility (90%
      versus 6%, P < 0.001). Of the 23 patients who successfully completed treatment,
      11 (48%) redeveloped NTM lung disease, with mycobacterial genotyping results
      indicating that the majority of cases were due to reinfection. Precise
      identification of etiologic NTM organisms could help predict treatment outcomes
      in patients with NTM-LD due to mixed infections.

PMID- 30104266
TI  - Loss-of-Function Mutations in epaR Confer Resistance to phiNPV1 Infection in
      Enterococcus faecalis OG1RF.
AB  - Enterococcus faecalis is a Gram-positive opportunistic pathogen that inhabits the
      human gastrointestinal tract. Because of the high frequency of antibiotic
      resistance among Enterococcus clinical isolates, interest in using phage to treat
      enterococcal infections and to decolonize high-risk patients for antibiotic
      resistant Enterococcus is rising. Bacteria can evolve phage resistance, but there
      is little published information on these mechanisms in E. faecalis In this
      report, we identified genetic determinants of E. faecalis resistance to phage
      NPV1 (phiNPV1). We found that loss-of-function mutations in epaR confer phiNPV1
      resistance by blocking phage adsorption. We attribute the inability of the phage
      to adsorb to the modification or loss of an extracellular polymer in strains with
      inactivated epaR Phage-resistant epaR mutants exhibited increased daptomycin and
      osmotic stress susceptibilities. Our results demonstrate that in vitro
      spontaneous resistance to phiNPV1 comes at a cost in E. faecalis OG1RF.

PMID- 30104267
TI  - Can We Improve Stavudine's Safety Profile in Children? Pharmacokinetics of
      Intracellular Stavudine Triphosphate with Reduced Dosing.
AB  - Stavudine remains a useful replacement option for treatment for HIV+ children.
      WHO reduced the adult dose to 30 mg twice daily, which maintains efficacy and
      lowers mitochondrial toxicity. We explored intracellular stavudine triphosphate
      levels in children receiving a reduced dose of 0.5 to 0.75 mg/kg of body weight
      twice daily to investigate whether a similar dose optimization can safely be
      made. A population pharmacokinetic model was developed to describe the
      pharmacokinetics of intracellular stavudine triphosphate in 23 HIV+ children and
      24 HIV+ adults who received stavudine at 0.5 mg/kg and 20 mg twice daily for 7
      days, respectively. Simulations were employed to optimize the pediatric dosing
      regimen to match exposures in adults receiving the current WHO-recommended dose
      of 30 mg twice daily. A biphasic disposition model with first-order appearance
      and disappearance described the pharmacokinetics of stavudine triphosphate. The
      use of allometric scaling with fat-free mass characterized well the
      pharmacokinetics in both adults and children, and no other significant effect
      could be detected. Simulations of 30 mg twice daily in adults predicted median
      (interquartile range [IQR]) stavudine triphosphate minimum drug concentration (C
      min) and maximum drug concentration (C max) values of 13 (10 to 19) and 45 (38 to
      53) fmol/106 cells, respectively. Targeting this exposure, simulations in HIV+
      children were used to identify a suitable weight-band dosing approach (0.5 to
      0.75 mg/kg), which was predicted to achieve median (IQR) C min and C max values
      of 13 (9 to 18) and 49 (40 to 58) fmol/106 cells, respectively. Weight-band
      dosing using a stavudine dose of 0.5 to 0.75 mg/kg is proposed, and it shows
      comparable exposures to adults receiving the current WHO-recommended dose of 30
      mg twice daily. Our pharmacokinetic results suggest that the decreased stavudine
      dose in children >2 years would have a reduced toxic effect while retaining
      antiretroviral efficacy.

PMID- 30104268
TI  - Minocycline Has No Clear Role in the Treatment of Mycobacterium abscessus
      Disease.
AB  - Mycobacterium abscessus causes a difficult-to-treat pulmonary disease (MAb-PD).
      After initial intravenous treatment, minocycline is recommended in the oral
      continuation phase of treatment. We determined the MICs, synergy, and time-kill
      kinetics of minocycline against M. abscessus With MICs of 8 to 512 mg/liter,
      rapid emergence of tolerance in time-kill assays, and no synergy with other drugs
      used to treat MAb-PD, minocycline appears ineffective against M. abscessus These
      in vitro data question its role as a MAb-PD treatment modality.

PMID- 30104269
TI  - Screening a Repurposing Library for Inhibitors of Multidrug-Resistant Candida
      auris Identifies Ebselen as a Repositionable Candidate for Antifungal Drug
      Development.
AB  - Since its original isolation in 2009, Candida auris has spread across the globe
      as a causative agent of invasive candidiasis. C. auris is typically intrinsically
      resistant to fluconazole and can also be resistant to echinocandins and even
      amphotericin B. Thus, there is an urgent need to find new treatment options
      against this emerging pathogen. To address this growing problem, we performed a
      screen of the Prestwick Chemical library, a repurposing library of 1,280 small
      molecules, consisting mostly of approved off-patent drugs, in search of those
      with activity against a multidrug-resistant C. auris isolate. Our initial screen,
      using standardized susceptibility testing methodologies, identified nine
      miscellaneous compounds with no previous clinical indication as antifungals or
      antiseptics that displayed activity against C. auris Confirmation and follow-up
      studies identified ebselen as the drug displaying the most potent activity, with
      100% inhibition of growth detected at concentrations as low as 2.5 MUM. We
      further evaluated the ability of ebselen to inhibit C. auris biofilm formation
      and examined the effects of combination therapies of ebselen with clinically used
      antifungals. We extended our studies to different C. auris strains with various
      susceptibility patterns and also confirmed its antifungal activity against
      Candida albicans and clinical isolates of multiple other Candida species.
      Furthermore, ebselen displayed a broad spectrum of antifungal actions on the
      basis of its activity against a variety of medically important fungi, including
      yeasts and molds. Overall, our results indicate the promise of ebselen as a
      repositionable agent for the treatment of candidiasis and possibly other mycoses
      and, in particular, for the treatment of infections refractory to conventional
      treatment with current antifungals.

PMID- 30104270
TI  - Cyclic Nucleotide-Specific Phosphodiesterases as Potential Drug Targets for Anti
      Leishmania Therapy.
AB  - The available treatments for leishmaniasis are less than optimal due to
      inadequate efficacy, toxic side effects, and the emergence of resistant strains,
      clearly endorsing the urgent need for discovery and development of novel drug
      candidates. Ideally, these should act via an alternative mechanism of action to
      avoid cross-resistance with the current drugs. As cyclic nucleotide-specific
      phosphodiesterases (PDEs) of Leishmania major have been postulated as putative
      drug targets, a series of potential inhibitors of Leishmania PDEs were explored.
      Several displayed potent and selective in vitro activity against L. infantum
      intracellular amastigotes. One imidazole derivative, compound 35, was shown to
      reduce the parasite loads in vivo and to increase the cellular cyclic AMP (cAMP)
      level at in a dose-dependent manner at just 2* and 5* the 50% inhibitory
      concentration (IC50), indicating a correlation between antileishmanial activity
      and increased cellular cAMP levels. Docking studies and molecular dynamics
      simulations pointed to imidazole 35 exerting its activity through PDE inhibition.
      This study establishes for the first time that inhibition of cAMP PDEs can
      potentially be exploited for new antileishmanial chemotherapy.

PMID- 30104271
TI  - Efficacy and Safety of Low-Dose Liposomal Amphotericin B in Adult Patients
      Undergoing Unrelated Cord Blood Transplantation.
AB  - Liposomal amphotericin B (L-AMB) is widely used for empirical or preemptive
      therapy and treatment of invasive fungal infections after cord blood
      transplantation (CBT). We retrospectively examined the efficacy and safety of low
      dose L-AMB in 48 adult patients who underwent CBT between 2006 and 2017 in our
      institute. Within the entire cohort, 42 patients (88%) received L-AMB as
      empirical or preemptive therapy. The median daily dose of L-AMB and the median
      cumulative dose of L-AMB were 1.20 mg/kg/day (range, 0.62 to 2.60 mg/kg/day) and
      30.6 mg/kg (range, 0.7 to 241.5 mg/kg), respectively. The median duration of L
      AMB administration was 21.5 days (range, 1 to 313 days). A documented
      breakthrough fungal infection occurred in 1 patient during L-AMB treatment, and
      43 patients (90%) survived for at least 7 days after the end of L-AMB treatment.
      Grade 3 or higher hypokalemia and hepatotoxicity were frequently observed during
      L-AMB treatment. However, no patient developed an increase in serum creatinine
      levels of grade 3 or higher. In univariate analyses using a logistic regression
      model, a duration of L-AMB treatment of more than 21 days and a cumulative dose
      of L-AMB of more than 30 mg/kg were significantly associated with nephrotoxicity
      and grade 3 hypokalemia. These data suggest that low-dose L-AMB may be safe and
      effective in adult patients undergoing CBT.

PMID- 30104272
TI  - Treatment of Pseudomonas aeruginosa Biofilm Present in Endotracheal Tubes by Poly
      l-Lysine.
AB  - The endotracheal tube (ETT) is an essential interface between the patient and
      ventilator in mechanically ventilated patients. However, a microbial biofilm is
      formed gradually on this tube and is associated with the development of
      ventilator-associated pneumonia. The bacteria present in the biofilm are more
      resistant to antibiotics, and current medical practices do not make it possible
      to eliminate. Pseudomonas aeruginosa is one of the leading pathogens that cause
      biofilm infections and ventilator-associated pneumonia. Poly-l-lysine (pLK) is a
      cationic polypeptide possessing antibacterial properties and mucolytic activity
      by compacting DNA. Here, we explored the antibiofilm activity of pLK to treat P.
      aeruginosa biofilms on ETTs while taking into consideration the necessary
      constraints for clinical translation in our experimental designs. First, we
      showed that pLK eradicates a P. aeruginosa biofilm formed in vitro on 96-well
      microplates. We further demonstrated that pLK alters bacterial membrane
      integrity, as revealed by scanning electron microscopy, and eventually eradicates
      biofilm formed either by reference or clinical strains of P. aeruginosa biofilms
      generated in vitro on ETTs. Second, we collected the ETT from patients with P.
      aeruginosa ventilator-associated pneumonia. We observed that a single dose of pLK
      is able to immediately disrupt the biofilm structure and kills more than 90% of
      bacteria present in the biofilm. Additionally, we did not observe any lung
      tolerance issue when the pLK solution was instilled into the ETT of ventilated
      pigs, an animal model particularly relevant to mimic invasive mechanical
      ventilation in humans. In conclusion, pLK appears as an innovative antibiofilm
      molecule, which could be applied in the ETT of mechanically ventilated patients.

PMID- 30104273
TI  - Candida albicans Zn Cluster Transcription Factors Tac1 and Znc1 Are Activated by
      Farnesol To Upregulate a Transcriptional Program Including the Multidrug Efflux
      Pump CDR1.
AB  - Farnesol, a quorum-sensing molecule, inhibits Candida albicans hyphal formation,
      affects its biofilm formation and dispersal, and impacts its stress response.
      Several aspects of farnesol's mechanism of action remain incompletely
      uncharacterized. Among these are a thorough accounting of the cellular receptors
      and transporters for farnesol. This work suggests these processes are linked
      through the Zn cluster transcription factors Tac1 and Znc1 and their induction of
      the multidrug efflux pump Cdr1. Specifically, we have demonstrated that Tac1 and
      Znc1 are functionally activated by farnesol through a mechanism that mimics other
      means of hyperactivation of Zn cluster transcription factors. This is consistent
      with our observation that many genes acutely induced by farnesol are dependent on
      TAC1, ZNC1, or both. A related molecule, 1-dodecanol, invokes a similar TAC1-ZNC1
      response, while several other proposed C. albicans quorum-sensing molecules do
      not. Tac1 and Znc1 both bind to and upregulate the CDR1 promoter in response to
      farnesol. Differences in inducer and DNA binding specificity lead to Tac1 and
      Znc1 having overlapping, but nonidentical, regulons. Induction of genes by
      farnesol via Tac1 and Znc1 was inversely related to the level of CDR1 present in
      the cell, suggesting a model in which induction of CDR1 by Tac1 and Znc1 leads to
      an increase in farnesol efflux. Consistent with this premise, our results show
      that CDR1 expression, and its regulation by TAC1 and ZNC1, facilitates growth in
      the presence of high farnesol concentrations in C. albicans and in certain
      strains of its close relative, C. dubliniensis.

PMID- 30104274
TI  - Disrupting Gram-Negative Bacterial Outer Membrane Biosynthesis through Inhibition
      of the Lipopolysaccharide Transporter MsbA.
AB  - There is a critical need for new antibacterial strategies to counter the growing
      problem of antibiotic resistance. In Gram-negative bacteria, the outer membrane
      (OM) provides a protective barrier against antibiotics and other environmental
      insults. The outer leaflet of the outer membrane is primarily composed of
      lipopolysaccharide (LPS). Outer membrane biogenesis presents many potentially
      compelling drug targets as this pathway is absent in higher eukaryotes. Most
      proteins involved in LPS biosynthesis and transport are essential; however, few
      compounds have been identified that inhibit these proteins. The inner membrane
      ABC transporter MsbA carries out the first essential step in the trafficking of
      LPS to the outer membrane. We conducted a biochemical screen for inhibitors of
      MsbA and identified a series of quinoline compounds that kill Escherichia coli
      through inhibition of its ATPase and transport activity, with no loss of activity
      against clinical multidrug-resistant strains. Identification of these selective
      inhibitors indicates that MsbA is a viable target for new antibiotics, and the
      compounds we identified serve as useful tools to further probe the LPS transport
      pathway in Gram-negative bacteria.

PMID- 30104275
TI  - Nitazoxanide Inhibits Human Norovirus Replication and Synergizes with Ribavirin
      by Activation of Cellular Antiviral Response.
AB  - Norovirus is the main cause of viral gastroenteritis worldwide. Although
      norovirus gastroenteritis is self-limiting in immunocompetent individuals,
      chronic infections with debilitating and life-threatening complications occur in
      immunocompromised patients. Nitazoxanide (NTZ) has been used empirically in the
      clinic and has demonstrated effectiveness against norovirus gastroenteritis. In
      this study, we aimed at uncovering the antiviral potential and mechanisms of
      action of NTZ and its active metabolite, tizoxanide (TIZ), using a human
      norovirus (HuNV) replicon. NTZ and TIZ, collectively referred to as thiazolides
      (TZD), potently inhibited replication of HuNV and a norovirus surrogate, feline
      calicivirus. Mechanistic studies revealed that TZD activated cellular antiviral
      response and stimulated the expression of a subset of interferon-stimulated genes
      (ISGs), particularly interferon regulatory factor 1 (IRF-1), not only in a Huh7
      cell-based HuNV replicon, but also in naive Huh7 and Caco-2 cells and novel human
      intestinal organoids. Overexpression of exogenous IRF-1 inhibited HuNV
      replication, whereas knockdown of IRF-1 largely attenuated the antiviral activity
      of TZD, suggesting that IRF-1 mediated TZD inhibition of HuNV. By using a Janus
      kinase (JAK) inhibitor, CP-690550, and a STAT1 knockout approach, we found that
      TZD induced antiviral response independently of the classical JAK-signal
      transducers and activators of transcription (JAK-STAT) pathway. Furthermore, TZD
      and ribavirin synergized to inhibit HuNV replication and completely depleted the
      replicons from host cells after long-term treatment. In summary, our results
      demonstrated that TZD combated HuNV replication through activation of cellular
      antiviral response, in particular by inducing a prominent antiviral effector, IRF
      1. NTZ monotherapy or combination with ribavirin represent promising options for
      treating norovirus gastroenteritis, especially in immunocompromised patients.

PMID- 30104276
TI  - Synthetic Ingenols Maximize Protein Kinase C-Induced HIV-1 Latency Reversal.
AB  - Antiretroviral therapy (ART) does not cure HIV-1 infection due to the persistence
      of proviruses in long-lived resting T cells. Strategies targeting these latently
      infected cells will be necessary to eradicate HIV-1 in infected individuals.
      Protein kinase C (PKC) activation is an effective mechanism to reactivate latent
      proviruses and allows for recognition and clearance of infected cells by the
      immune system. Several ingenol compounds, naturally occurring PKC agonists, have
      been described to have potent latency reversal activity. We sought to optimize
      this activity by synthesizing a library of novel ingenols via esterification of
      the C-3 hydroxyl group of the ingenol core, which itself is inactive for latency
      reversal. Newly synthesized ingenol derivatives were evaluated for latency
      reversal activity, cellular activation, and cytotoxicity alongside commercially
      available ingenols (ingenol-3,20-dibenzoate, ingenol 3-hexanoate, and ingenol-3
      angelate) in HIV latency cell lines and resting CD4+ T cells from aviremic
      participants. Among the synthetic ingenols that we produced, we identified
      several compounds that demonstrate high efficacy and represent promising leads as
      latency reversal agents for HIV-1 eradication.

PMID- 30104277
TI  - Activity of Aromathecins against African Trypanosomes.
AB  - African sleeping sickness is responsible for thousands of deaths annually, and
      new therapeutics are needed. This study evaluated aromathecins, experimental
      inhibitors of mammalian topoisomerase IB, against Trypanosoma brucei African
      trypanosomes. The compounds had selectively toxic antiparasitic potency, in situ
      poisoning activity against the phylogenetically unique topoisomerase in these
      parasites, and a representative compound intercalated into DNA with micromolar
      affinity. DNA intercalation and topoisomerase poisoning may contribute to the
      antitrypanosomal activity of aromathecins.

PMID- 30104279
TI  - In Vitro Activities of the Benzoquinolizine Fluoroquinolone Levonadifloxacin (WCK
      771) and Other Antimicrobial Agents against Mycoplasmas and Ureaplasmas in
      Humans, Including Isolates with Defined Resistance Mechanisms.
AB  - Levonadifloxacin (WCK 771) was evaluated against 68 type strains and clinical
      isolates of Mycoplasma genitalium, Mycoplasma hominis, Mycoplasma pneumoniae, and
      Ureaplasma spp. in comparison with moxifloxacin, levofloxacin, tetracycline, and
      azithromycin or clindamycin. Levonadifloxacin MICs were <=0.5 MUg/ml for M.
      genitalium MIC90s were 1 MUg/ml for M. hominis, 0.125 MUg/ml for M. pneumoniae,
      and 2 MUg/ml for Ureaplasma spp. Levonadifloxacin merits further study for
      treating infections caused by these organisms.

PMID- 30104278
TI  - Meropenem Combined with Ciprofloxacin Combats Hypermutable Pseudomonas aeruginosa
      from Respiratory Infections of Cystic Fibrosis Patients.
AB  - Hypermutable Pseudomonas aeruginosa organisms are prevalent in chronic
      respiratory infections and have been associated with reduced lung function in
      cystic fibrosis (CF); these isolates can become resistant to all antibiotics in
      monotherapy. This study aimed to evaluate the time course of bacterial killing
      and resistance of meropenem and ciprofloxacin in combination against hypermutable
      and nonhypermutable P. aeruginosa Static concentration time-kill experiments over
      72 h assessed meropenem and ciprofloxacin in mono- and combination therapies
      against PAO1 (nonhypermutable), PAODeltamutS (hypermutable), and hypermutable
      isolates CW8, CW35, and CW44 obtained from CF patients with chronic respiratory
      infections. Meropenem (1 or 2 g every 8 h [q8h] as 3-h infusions and 3 g/day as a
      continuous infusion) and ciprofloxacin (400 mg q8h as 1-h infusions) in
      monotherapies and combinations were further evaluated in an 8-day hollow-fiber
      infection model study (HFIM) against CW44. Concentration-time profiles in lung
      epithelial lining fluid reflecting the pharmacokinetics in CF patients were
      simulated and counts of total and resistant bacteria determined. All data were
      analyzed by mechanism-based modeling (MBM). In the HFIM, all monotherapies
      resulted in rapid regrowth with resistance at 48 h. The maximum daily doses of 6
      g meropenem (T>MIC of 80% to 88%) and 1.2 g ciprofloxacin (area under the
      concentration-time curve over 24 h in the steady state divided by the MIC
      [AUC/MIC], 176), both given intermittently, in monotherapy failed to suppress
      regrowth and resulted in substantial emergence of resistance (>=7.6 log10 CFU/ml
      resistant populations). The combination of these regimens achieved synergistic
      killing and suppressed resistance. MBM with subpopulation and mechanistic synergy
      yielded unbiased and precise curve fits. Thus, the combination of 6 g/day
      meropenem plus ciprofloxacin holds promise for future clinical evaluation against
      infections by susceptible hypermutable P. aeruginosa.

PMID- 30104281
TI  - Case Report of Successful Treatment of Extensively Drug-Resistant Acinetobacter
      baumannii Ventriculitis with Intravenous plus Intraventricular Tigecycline.

PMID- 30104280
TI  - In Vivo Efficacy of VT-1129 against Experimental Cryptococcal Meningitis with the
      Use of a Loading Dose-Maintenance Dose Administration Strategy.
AB  - VT-1129 is a novel fungal enzyme-specific Cyp51 inhibitor with potent
      cryptococcal activity. Because of its long half-life (>6 days in mice) and our
      desire to quickly reach potent efficacy, we evaluated a VT-1129 loading dose
      maintenance dose strategy against cryptococcal meningitis. VT-1129 plasma and
      brain pharmacokinetics were first studied in healthy mice, and these data were
      used to model loading dose-maintenance dose regimens to generate different steady
      state concentrations. Mice were inoculated intracranially with Cryptococcus
      neoformans, and oral treatment began 1 day later. Treatment consisted of placebo
      or one of three VT-1129 loading dose-maintenance dose regimens, i.e., loading
      dose of 1, 3, or 30 mg/kg on day 1, followed by once-daily maintenance doses of
      0.15, 0.5, or 5 mg/kg, respectively. In the fungal burden arm, therapy continued
      for 14 days and brains were collected on day 15 for fungal burden assessments. In
      the survival arm, treatment continued for 10 days, after which mice were
      monitored without therapy until day 30. VT-1129 plasma and brain concentrations
      were also measured. All VT-1129 doses significantly improved survival and reduced
      fungal burdens, compared to placebo. VT-1129 plasma and brain levels correlated
      with fungal burden reductions (R 2 = 0.72 and R 2 = 0.67, respectively), with a
      plasma concentration of 1 MUg/ml yielding a reduction of ~5 log10 CFU/g. With the
      highest loading dose-maintenance dose regimen, fungal burdens were undetectable
      in one-half of the mice in the fungal burden arm and in one-fourth of the mice in
      the survival arm, 20 days after the final dose. These data support a loading dose
      maintenance dose strategy for quickly reaching highly efficacious VT-1129
      concentrations for treating cryptococcal meningitis.

PMID- 30104283
TI  - Biocompatibility and Targeting Efficiency of Encapsulated Quinapyramine Sulfate
      Loaded Chitosan-Mannitol Nanoparticles in a Rabbit Model of Surra.
AB  - Quinapyramine sulfate (QS) produces trypanocidal effects against the parasite
      Trypanosoma evansi but is often poorly tolerated and causes serious reactions in
      animals. The encapsulation of QS in chitosan-mannitol to provide sustained
      release would improve both the therapeutic effect of QS and the quality of life
      of animals treated with this formulation. QS was encapsulated into a
      nanoformulation prepared from chitosan, tripolyphosphate, and mannitol nanomatrix
      (ChQS-NPs). ChQS-NPs were well ordered in shape, with nanoparticle size, as
      determined by transmission electron microscopy and atomic force microscopy. Our
      research revealed dose-dependent effects on biosafety and DNA damage in mammalian
      cells treated with ChQS-NPs. ChQS-NPs were absolutely risk-free at effective as
      well as many times higher doses against T. evansi ChQS-NPs were effective in
      rabbits, as they killed the parasites, relieving the animals from the clinical
      symptoms of the disease. The extent of this protection was similar to that
      observed with the conventional drug at higher dosages (5 mg QS/kg of body
      weight). ChQS-NPs are safe, nontoxic, and more effective than QS and offer a
      promising alternative to drug delivery against surra in animal models. ChQS-NPs
      may be useful for the treatment of surra due to reduced dosages and frequency of
      administration.

PMID- 30104282
TI  - Treatment of Infections by OXA-48-Producing Enterobacteriaceae.
AB  - Carbapenemase-producing Enterobacteriaceae (CPE) contribute significantly to the
      global public health threat of antimicrobial resistance. OXA-48 and its variants
      are unique carbapenemases with low-level hydrolytic activity toward carbapenems
      but no intrinsic activity against expanded-spectrum cephalosporins. bla OXA-48 is
      typically located on a plasmid but may also be integrated chromosomally, and this
      gene has progressively disseminated throughout Europe and the Middle East.
      Despite the inability of OXA-48-like carbapenemases to hydrolyze expanded
      spectrum cephalosporins, pooled isolates demonstrate high variable resistance to
      ceftazidime and cefepime, likely representing high rates of extended-spectrum
      beta-lactamase (ESBL) coproduction. In vitro data from pooled studies suggest
      that avibactam is the most potent beta-lactamase inhibitor when combined with
      ceftazidime, cefepime, aztreonam, meropenem, or imipenem. Resistance to novel
      avibactam combinations such as imipenem-avibactam or aztreonam-avibactam has not
      yet been reported in OXA-48 producers, although only a few clinical isolates have
      been tested. Although combination therapy is thought to improve the chances of
      clinical cure and survival in CPE infection, successful outcomes were seen in
      ~70% of patients with infections caused by OXA-48-producing Enterobacteriaceae
      treated with ceftazidime-avibactam monotherapy. A carbapenem in combination with
      either amikacin or colistin has achieved treatment success in a few case reports.
      Uncertainty remains regarding the best treatment options and strategies for
      managing these infections. Newly available antibiotics such as ceftazidime
      avibactam show promise; however, recent reports of resistance are concerning.
      Newer choices of antimicrobial agents will likely be required to combat this
      problem.

PMID- 30104285
TI  - AI system interprets eye scans as accurately as top specialists.

PMID- 30104284
TI  - Noncanonical secondary structures arising from non-B DNA motifs are determinants
      of mutagenesis.
AB  - Somatic mutations show variation in density across cancer genomes. Previous
      studies have shown that chromatin organization and replication time domains are
      correlated with, and thus predictive of, this variation. Here, we analyze 1809
      whole-genome sequences from 10 cancer types to show that a subset of repetitive
      DNA sequences, called non-B motifs that predict noncanonical secondary structure
      formation can independently account for variation in mutation density. Combined
      with epigenetic factors and replication timing, the variance explained can be
      improved to 43%-76%. Approximately twofold mutation enrichment is observed
      directly within non-B motifs, is focused on exposed structural components, and is
      dependent on physical properties that are optimal for secondary structure
      formation. Therefore, there is mounting evidence that secondary structures
      arising from non-B motifs are not simply associated with increased mutation
      density-they are possibly causally implicated. Our results suggest that they are
      determinants of mutagenesis and increase the likelihood of recurrent mutations in
      the genome. This analysis calls for caution in the interpretation of recurrent
      mutations and highlights the importance of taking non-B motifs that can simply be
      inferred from the reference sequence into consideration in background models of
      mutability henceforth.

PMID- 30104287
TI  - Sixty seconds on . . . life expectancy.

PMID- 30104288
TI  - The Evolving Treatment Algorithm for Advanced Neuroendocrine Neoplasms: Diversity
      and Commonalities Across Tumor Types.
AB  - : Neuroendocrine neoplasms (NEN) most commonly arise in the
      gastroenteropancreatic system and lungs. The incidence of NEN is increasing
      globally, with improved diagnostic techniques identifying patients with early
      stage disease. The number of approved therapies for the treatment of advanced
      disease has grown substantially in the past decade. The treatment algorithm for
      advanced NEN is evolving from one that is directed by primary site-specific
      classification to one that is directed by biologic classification, as evidenced
      by overlapping systemic treatments across the primary tumor sites. Commonalities
      in biologic characteristics across primary sites include functional status,
      differentiation status, grade, level of somatostatin receptor expression, and
      genetic alterations. In this review, we discuss current clinical evidence and
      available therapies for the treatment of advanced NEN and highlight the need for
      prospective trials in patients with well-differentiated, high-grade NEN.
      IMPLICATIONS FOR PRACTICE: This review raises awareness of the evolution of the
      treatment algorithm for advanced neuroendocrine neoplasms (NEN) from one that is
      directed by primary tumor site-specific classification to one that is directed by
      biologic classification. In addition, this review promotes understanding of the
      new pathologic category of well-differentiated G3 pancreatic neuroendocrine
      tumors and highlights the need for prospective trials in this patient population,
      for whom there is currently no standard of care. This review further provides a
      conceptual treatment schematic that categorizes the recommendations for systemic
      treatments for advanced disease by biologic classification, including the new and
      established categories of NEN.

PMID- 30104286
TI  - CDK12: an emerging therapeutic target for cancer.
AB  - Cyclin-dependent kinase 12 (CDK12) belongs to the cyclin-dependent kinase (CDK)
      family of serine/threonine protein kinases that regulate transcriptional and post
      transcriptional processes, thereby modulating multiple cellular functions. Early
      studies characterised CDK12 as a transcriptional CDK that complexes with cyclin K
      to mediate gene transcription by phosphorylating RNA polymerase II. CDK12 has
      been demonstrated to specifically upregulate the expression of genes involved in
      response to DNA damage, stress and heat shock. More recent studies have
      implicated CDK12 in regulating mRNA splicing, 3' end processing, pre-replication
      complex assembly and genomic stability during embryonic development. Genomic
      alterations in CDK12 have been detected in oesophageal, stomach, breast,
      endometrial, uterine, ovarian, bladder, colorectal and pancreatic cancers,
      ranging from 5% to 15% of sequenced cases. An increasing number of studies point
      to CDK12 inhibition as an effective strategy to inhibit tumour growth, and
      synthetic lethal interactions have been described with MYC, EWS/FLI and PARP/CHK1
      inhibition. Herein, we discuss the present literature on CDK12 in cell function
      and human cancer, highlighting important roles for CDK12 as a clinical biomarker
      for treatment response and potential as an effective therapeutic target.

PMID- 30104289
TI  - Prospective Assessment of Clinical Risk Factors and Biomarkers of
      Hypercoagulability for the Identification of Patients with Lung Adenocarcinoma at
      Risk for Cancer-Associated Thrombosis: The Observational ROADMAP-CAT Study.
AB  - BACKGROUND: The aim of this prospective study was to identify the most clinically
      relevant hypercoagulability biomarkers in lung adenocarcinoma patients for
      elaboration of an improved risk assessment model (RAM) for venous thromboembolism
      (VTE). SUBJECTS, MATERIALS, AND METHODS: One hundred fifty ambulatory patients
      with lung adenocarcinoma were prospectively enrolled. Thrombin generation,
      procoagulant phospholipid-dependent clotting time (Procoag-PPL), tissue factor
      activity (TFa), factor VIIa (FVIIa), factor V (FV), antithrombin, D-Dimers, P
      selectin, and heparanase levels were assessed in platelet-poor plasma at
      inclusion (baseline) and at the end of the third chemotherapy cycle (third
      chemotherapy). Cox regression analysis was used to identify independent VTE
      predictors. RESULTS: At baseline, patients had significantly attenuated thrombin
      generation, shorter Procoag-PPL, higher levels of TFa, D-Dimers, and heparanase,
      and lower levels of FVIIa and P-selectin, compared with controls. A significant
      increase in Procoag-PPL, FV, and FVIIa and a decrease of P-selectin levels were
      observed between baseline and third chemotherapy. Hospitalization within the last
      3 months prior to assessment, time since cancer diagnosis less than 6 months,
      mean rate index (MRI) of thrombin generation, and Procoag-PPL were independently
      associated with symptomatic VTE. Accordingly, a prediction model including
      Procoag-PPL and MRI showed significant discriminating capacity (area under the
      curve: 0.84). CONCLUSION: Ambulatory patients with lung adenocarcinoma may
      display pronounced blood hypercoagulability due to decreased Procoag-PPL,
      increased endothelial cell activation, and increased degradation of fibrin.
      Incorporation of Procoag-PPL and MRI of thrombin generation may improve the
      accuracy of a VTE-RAM in the above setting. IMPLICATIONS FOR PRACTICE: The
      prospective ROADMAP-CAT study identified two biomarkers of hypercoagulability,
      the procoagulant phospholipid-dependent clotting time (Procoag-PPL) and the mean
      rate index (MRI) of the propagation phase of thrombin generation assessed with
      the Calibrated Automated Thrombinoscope, as being clinically relevant for the
      classification of ambulatory patients with lung adenocarcinoma receiving a
      maximum of one cycle of chemotherapy into high and intermediate/low risk for
      venous thromboembolism. Measurement of Procoag-PPL and MRI within 1 month after
      the administration of the first chemotherapy cycle provides significant accuracy
      of the assessment. Association of the Procoag-PPL and MRI with the clinical risk
      assessment model for cancer-associated thrombosis in ambulatory patients with
      solid tumors (COMPASS-CAT RAM) further improved its accuracy.

PMID- 30104290
TI  - Dramatic Response to Concurrent Anti-PD-1 Therapy and Radiation in Resistant
      Tumors with Sarcomatoid Differentiation.
AB  - A substantial fraction of patients demonstrate resistance to immune checkpoint
      inhibitors, which limits their use. Use of radiation concurrently with checkpoint
      inhibitors has been shown to boost immune responsiveness, resulting in
      significant tumor regression in patients with metastatic melanoma. However, it is
      unknown whether radiation could play a role in reversing the inherent resistance
      to checkpoint inhibition in certain tumor types. Most trials testing this
      concurrent approach exclude such modestly responsive tumors and pursue checkpoint
      inhibition using anti-cytotoxic T-lymphocyte-associated protein 4 antibody (anti
      CTLA-4, ipilimumab). The efficacy of anti-programmed-death-1 (anti-PD-1) therapy
      when used concurrently with radiation is less known but remains an attractive
      option due to less autoimmune toxicity compared with CTLA-4 inhibition. In this
      first reported experience, we have safely and effectively combined anti-PD-1
      therapy (nivolumab) concurrently with radiation to treat two patients with
      relapsed sarcomatoid renal carcinoma and heavily pretreated pleomorphic sarcoma.
      Both patients experienced a dramatic response that was durable.

PMID- 30104291
TI  - Interleukin-2 Can Cure Kidney Cancer.

PMID- 30104293
TI  - Gaza shootings: an orthopaedic crisis and mass disability.

PMID- 30104292
TI  - Durable Response to Nivolumab in a Pediatric Patient with Refractory Glioblastoma
      and Constitutional Biallelic Mismatch Repair Deficiency.
AB  - : Primary brain tumors are a leading cause of cancer-related morbidity and
      mortality in children. Glioblastoma (GBM) is a high-grade astrocytoma that occurs
      in both children and adults and is associated with a poor prognosis. Despite
      extensive study in recent years, the clinical management of these tumors has
      remained largely unchanged, consisting of surgical resection, conventional
      chemotherapy, and radiotherapy. Although the etiology and genomic drivers in GBM
      are diverse, constitutional mismatch repair-deficiency (CMMRD) syndrome is a
      rare, recessively inherited disease with a predisposition to gliomagenesis. CMMRD
      results from biallelic mutations in one of the mismatch repair genes including
      mutL homolog 1 (MLH1), mutS homolog 2 (MSH2), mutS homolog 6 (MSH6), and post
      meiotic segregation increased 2 (PMS2). In this report, we present the case of a
      5-year-old female with GBM and CMMRD due to an MSH6 homozygous c.1883G>A
      mutation, who continues to experience an exceptional and durable response (9
      months) to the immune checkpoint inhibitor (ICPI) nivolumab. Our patient
      presented with acute neurologic decline and increased intracranial pressure.
      Neuroimaging studies revealed a large left frontoparietal mass requiring
      neurosurgical decompression and resection. Histopathologic analyses resulted in a
      diagnosis of de novo GBM that was BRAF wild type and negative for programmed
      death-ligand 1 protein expression. She received standard-of-care treatment with
      surgery, radiation therapy, and temozolomide; however, the tumor recurred 3
      months after the initial diagnosis. Molecular analyses of tumor and blood tissues
      revealed an MSH6 homozygous c.1883G>A mutation consistent with CMMRD. Given her
      CMMRD status, she was treated with nivolumab (3 mg/kg doses every 2 weeks for 36
      weeks) and showed a 60% reduction in tumor size, improved clinical symptoms, and
      an ongoing durable response lasting 10 months to date. Our study highlights a
      durable response to the ICPI nivolumab in a pediatric patient with
      recurrent/refractory CMMRD-associated GBM. We show that incorporating genomic
      and/or molecular testing for CMMRD into routine pediatric oncology clinical care
      can identify a subset of patients likely to benefit from ICPI. KEY POINTS:
      Constitutional mismatch repair-deficiency (CMMRD) syndrome, alternatively known
      as biallelic mismatch repair deficiency syndrome, occurs in subset of pediatric
      cancer patients, including those with primary brain tumors.Patients from Arab and
      other developing countries are predicted to have higher incidence of CMMRD due to
      high prevalence of consanguinity.Integration of molecular and/or genomic testing
      into routine clinical care for pediatric cancer patients is important to identify
      patients with CMMRD syndrome.Patient with CMMRD-associated cancers may show
      increased responsiveness to immune checkpoint inhibitors.To the authors'
      knowledge, this is the first report in the Arab world of a durable response to
      immune checkpoint inhibitors in a pediatric glioblastoma patient.

PMID- 30104294
TI  - More Similarities Than Differences Testing Insulin Glargine 300 Units/mL Versus
      Insulin Degludec 100 Units/mL in Insulin-Naive Type 2 Diabetes: The Randomized
      Head-to-Head BRIGHT Trial.
AB  - OBJECTIVE: To compare insulin glargine 300 units/mL (Gla-300) versus insulin
      degludec 100 units/mL (IDeg-100) in this first head-to-head randomized controlled
      trial. RESEARCH DESIGN AND METHODS: BRIGHT (NCT02738151) was a multicenter, open
      label, active-controlled, two-arm, parallel-group, 24-week, noninferiority study
      in insulin-naive patients with uncontrolled type 2 diabetes. Participants were
      randomized 1:1 to evening dosing with Gla-300 (N = 466) or IDeg-100 (N = 463),
      titrated to fasting self-monitored plasma glucose of 80-100 mg/dL. The primary
      end point was HbA1c change from baseline to week 24. Safety end points included
      incidence and event rates of hypoglycemia. RESULTS: At week 24, HbA1c improved
      similarly from baseline values of 8.7% (72 mmol/mol) in the Gla-300 group and
      8.6% (70 mmol/mol) in the IDeg-100 group to 7.0% (53 mmol/mol)-least squares mean
      difference -0.05% (95% CI -0.15 to 0.05) (-0.6 mmol/mol [-1.7 to 0.6])
      demonstrating noninferiority of Gla-300 versus IDeg-100 (P < 0.0001).
      Hypoglycemia incidence and event rates over 24 weeks were comparable with both
      insulins, whereas during the active titration period (0-12 weeks) the incidence
      and rate of anytime (24-h) confirmed hypoglycemia (<=70 and <54 mg/dL) were lower
      with Gla-300. Both insulins were properly titrated and exhibited no specific
      safety concerns. CONCLUSIONS: Gla-300 and IDeg-100 provided similar glycemic
      control improvements with relatively low hypoglycemia risk. Hypoglycemia
      incidence and rates were comparable with both insulins during the full study
      period but lower in favor of Gla-300 during the titration period. The choice
      between these longer-acting basal insulins may be determined by factors such as
      access and cost, alongside clinical considerations.

PMID- 30104295
TI  - Associations Between Oral Health Status and Diabetic Neuropathy in a Large
      Romanian Cohort of Patients With Diabetes.

PMID- 30104296
TI  - Glycemic Control and Risk of Infections Among People With Type 1 or Type 2
      Diabetes in a Large Primary Care Cohort Study.
AB  - OBJECTIVE: Diabetes mellitus (DM) increases the risk of infections, but the
      effect of better control has not been thoroughly investigated. RESEARCH DESIGN
      AND METHODS: With the use of English primary care data, average glycated
      hemoglobin (HbA1c) during 2008-2009 was estimated for 85,312 patients with DM
      ages 40-89 years. Infection rates during 2010-2015 compiled from primary care,
      linked hospital, and mortality records were estimated across 18 infection
      categories and further summarized as any requiring a prescription or
      hospitalization or as cause of death. Poisson regression was used to estimate
      adjusted incidence rate ratios (IRRs) by HbA1c categories across all DM, and type
      1 and type 2 DM separately. IRRs also were compared with 153,341 age-sex-practice
      matched controls without DM. Attributable fractions (AF%) among patients with DM
      were estimated for an optimal control scenario (HbA1c 6-7% [42-53 mmol/mol]).
      RESULTS: Long-term infection risk rose with increasing HbA1c for most outcomes.
      Compared with patients without DM, those with DM and optimal control (HbA1c 6-7%
      [42-53 mmol/mol], IRR 1.41 [95% CI 1.36-1.47]) and poor control (>=11% [97
      mmol/mol], 4.70 [4.24-5.21]) had elevated hospitalization risks for infection. In
      patients with type 1 DM and poor control, this risk was even greater (IRR 8.47
      [5.86-12.24]). Comparisons within patients with DM confirmed the risk of
      hospitalization with poor control (2.70 [2.43-3.00]) after adjustment for
      duration and other confounders. AF% of poor control were high for serious
      infections, particularly bone and joint (46%), endocarditis (26%), tuberculosis
      (24%), sepsis (21%), infection-related hospitalization (17%), and mortality
      (16%). CONCLUSIONS: Poor glycemic control is powerfully associated with serious
      infections and should be a high priority.

PMID- 30104297
TI  - New-Onset Diabetes After Acute Kidney Injury Requiring Dialysis.
AB  - OBJECTIVE: Acute kidney injury (AKI) is related to a high prevalence of insulin
      resistance. However, information is lacking on the sequelae of further metabolic
      change among AKI requiring dialysis in patients who could be weaned off dialysis
      (acute kidney disease [AKD]). RESEARCH DESIGN AND METHODS: Using the National
      Health Insurance Research Database from 2000 to 2010, with the exclusion of those
      with diabetes at the start, we identified 3,307 subjects with AKD and 9,921
      matched control subjects from 963,037 hospitalized patients for the comparison of
      the outcomes, including new-onset diabetes and all-cause mortality. RESULTS:
      Within the median follow-up period of 5.99 years, AKD patients had a higher
      incidence of new-onset diabetes than the matched control patients (5.16% vs.
      4.17% per person-year, P = 0.001). AKD patients were at higher risk of mortality
      than control patients (adjusted hazard ratio [aHR] 1.27 [95% CI 1.18-1.36], P <
      0.001). With mortality as a competing risk, a Cox proportional hazards analysis
      showed that AKD patients had a higher risk of subsequent diabetes (subhazard
      ratio [sHR] 1.18 [95% CI 1.07-1.30], P < 0.001) compared with the matched control
      patients. Subgroup analysis showed that patients with baseline hypertension (aHR
      1.15 [95% CI 1.04-1.28]), hyperlipidemia (aHR 1.23 [95% CI 1.02-1.48]), and gout
      (aHR 1.23 [95% CI 1.03-1.46]) had increased odds of developing new-onset diabetes
      during follow-up. CONCLUSIONS: Patients who experienced AKI had a higher
      incidence of developing new-onset diabetes and mortality. This observation adds
      evidence regarding potential metabolic dysregulation after AKI.

PMID- 30104299
TI  - Erratum. Mediterranean Diet, Retinopathy, Nephropathy, and Microvascular Diabetes
      Complications: A Post Hoc Analysis of a Randomized Trial. Diabetes Care
      2015;38:2134-2141.

PMID- 30104298
TI  - Burden of Urological Complications in Men and Women With Long-standing Type 1
      Diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes
      Interventions and Complications Cohort.
AB  - OBJECTIVE: Type 1 diabetes has been associated with high rates of urinary and
      sexual problems, but the cumulative burden and overlap of these complications are
      unknown. We sought to determine prevalence of urological complications in persons
      with type 1 diabetes, associations with clinical and diabetes-related factors,
      and rates of emergence, persistence, and remission. RESEARCH DESIGN AND METHODS:
      This ancillary longitudinal study among participants in the Diabetes Control and
      Complications Trial (DCCT) and observational follow-up study Epidemiology of
      Diabetes Interventions and Complications (EDIC) (652 women and 713 men) was
      conducted in 2003 and 2010/2011. Urinary incontinence (UI), lower urinary tract
      symptoms, urinary tract infection, female sexual dysfunction, erectile
      dysfunction, low male sexual desire, and orgasmic dysfunction were measured with
      validated instruments. Logistic regression determined association of
      complications with demographics and clinical characteristics. RESULTS: Of
      sexually active women completing the 2010/2011 survey, 35% reported no
      complications, 39% had one, 19% two, 5% three, and 2% four. In men, 31% had no
      complications, 36% had one, 22% two, 9% three, and 3% four. Sexual dysfunction
      was most prevalent (42% women and 45% men) followed by UI in women (31%) and low
      sexual desire in men (40%). Urological complications were associated with age,
      BMI, and HbA1c. Remission rates ranged from 4 to 12% over the 7-year interval
      between surveys. CONCLUSIONS: Urological complications are prevalent and
      frequently co-occur in persons with type 1 diabetes. Remission rates in a
      minority subset indicate a rationale for future studies to mitigate the onset or
      impact of urological complications of diabetes.

PMID- 30104300
TI  - Erratum. Reduction in the Incidence of Type 2 Diabetes With the Mediterranean
      Diet: Results of the PREDIMED-Reus nutrition intervention randomized trial.
      Diabetes Care 2011;34:14-19.

PMID- 30104301
TI  - The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future
      Complications (the Diabetes & Aging Study).
AB  - OBJECTIVE: To examine for a legacy effect of early glycemic control on diabetic
      complications and death. RESEARCH DESIGN AND METHODS: This cohort study of
      managed care patients with newly diagnosed type 2 diabetes and 10 years of
      survival (1997-2013, average follow-up 13.0 years, N = 34,737) examined
      associations between HbA1c <6.5% (<48 mmol/mol), 6.5% to <7.0% (48 to <53
      mmol/mol), 7.0% to <8.0% (53 to <64 mmol/mol), 8.0% to <9.0% (64 to <75
      mmol/mol), or >=9.0% (>=75 mmol/mol) for various periods of early exposure (0-1,
      0-2, 0-3, 0-4, 0-5, 0-6, and 0-7 years) and incident future microvascular (end
      stage renal disease, advanced eye disease, amputation) and macrovascular (stroke,
      heart disease/failure, vascular disease) events and death, adjusting for
      demographics, risk factors, comorbidities, and later HbA1c. RESULTS: Compared
      with HbA1c <6.5% (<48 mmol/mol) for the 0-1-year early exposure period, HbA1c
      levels >=6.5% (>=48 mmol/mol) were associated with increased microvascular and
      macrovascular events (e.g., HbA1c 6.5% to <7.0% [48 to <53 mmol/mol]
      microvascular: hazard ratio 1.204 [95% CI 1.063-1.365]), and HbA1c levels >=7.0%
      (>=53 mmol/mol) were associated with increased mortality (e.g., HbA1c 7.0% to
      <8.0% [53 to <64 mmol/mol]: 1.290 [1.104-1.507]). Longer periods of exposure to
      HbA1c levels >=8.0% (>=64 mmol/mol) were associated with increasing microvascular
      event and mortality risk. CONCLUSIONS: Among patients with newly diagnosed
      diabetes and 10 years of survival, HbA1c levels >=6.5% (>=48 mmol/mol) for the
      1st year after diagnosis were associated with worse outcomes. Immediate,
      intensive treatment for newly diagnosed patients may be necessary to avoid
      irremediable long-term risk for diabetic complications and mortality.

PMID- 30104303
TI  - Effects of temperature on the timing of breeding and molt transitions in house
      finches.
AB  - Temperature-correlated shifts in reproductive timing are now well documented in
      numerous bird species. However, whether temperature directly influences
      reproductive timing or whether its effects are mediated by an intermediate
      environmental cue, such as plant phenology, remains poorly understood. In this
      study, we investigated the direct effects of temperature on reproductive timing
      in house finches (Haemorhous mexicanus), which have a range and breeding diet not
      well represented in previous studies of temperature and reproductive timing. We
      conducted experiments with captive male house finches in which temperature was
      elevated within realistic ranges and the effects on the timing of preparations
      for reproduction, as well as on the termination of reproduction and the onset of
      prebasic feather molt, were examined. We found no adjustments in the timing of
      reproductive preparations of males in direct response to temperature. However,
      elevated temperature did advance the breeding-molt transition. Our results
      suggest that elevated temperatures in the range tested here do not directly
      impact physiological preparations for reproduction in male house finches, but may
      constrain the timing of the breeding-molt transition in this species.

PMID- 30104302
TI  - Blood pressure in the Greenland shark as estimated from ventral aortic
      elasticity.
AB  - We conducted in vitro inflations of freshly excised ventral aortas of the
      Greenland shark, Somniosus microcephalus, and used pressure-diameter data to
      estimate the point of transition from high to low compliance, which has been
      shown to occur at the mean blood pressure in other vertebrates including fishes.
      We also determined the pressure at which the modulus of elasticity of the aorta
      reached 0.4 MPa, as occurs at the compliance transition in other species. From
      these analyses, we predict the average ventral aortic blood pressure in S.
      microcephalus to be about 2.3-2.8 kPa, much lower than reported for other sharks.
      Our results support the idea that this species is slow moving and has a
      relatively low aerobic metabolism. Histological investigation of the ventral
      aorta shows that elastic fibres are present in relatively low abundance and
      loosely connected, consistent with this aorta having high compliance at a
      relatively low blood pressure.

PMID- 30104304
TI  - Effects of organism and substrate size on burial mechanics of English sole,
      Parophrys vetulus.
AB  - Flatfishes use cyclic body undulations to force water into the sediment and
      fluidize substrate particles, displacing them into the water column. When water
      velocity decreases, suspended particles settle back onto the fish, hiding it from
      view. Burial may become more challenging as flatfishes grow because the area to
      be covered increases exponentially with the second power of length. In addition,
      particle size is not uniform in naturally occurring substrates, and larger
      particles require higher water velocities for fluidization. We quantified the
      effects of organism and particle-size scaling on burial behavior of English sole,
      Parophrys vetulus We recorded burial events from a size range of individuals (5
      32 cm total length, TL), while maintaining constant substrate grain size. Larger
      fish used lower cycle frequencies and took longer to bury, but overall burial
      performance was maintained (~100% coverage). To test the effect of particle size
      on burial performance, individuals of similar lengths (5.7-8.1 cm TL) were
      presented with different substrate sizes (0.125-0.710 mm). Particle size did not
      affect cycle frequency or time to burial, but fish did not achieve 100% coverage
      with the largest particles because they could not fluidize this substrate. Taken
      together, these results suggest that both body size and substrate grain size can
      potentially limit the ability of flatfishes to bury: a very large fish (>150 cm)
      may move too slowly to fluidize all but the smallest substrate particles and some
      particles are simply too large for smaller individuals to fluidize.

PMID- 30104306
TI  - Anti-diuretic activity of a CAPA neuropeptide can compromise Drosophila chill
      tolerance.
AB  - For insects, chilling injuries that occur in the absence of freezing are often
      related to a systemic loss of ion and water balance that leads to extracellular
      hyperkalemia, cell depolarization and the triggering of apoptotic signalling
      cascades. The ability of insect ionoregulatory organs (e.g. the Malpighian
      tubules) to maintain ion balance in the cold has been linked to improved chill
      tolerance, and many neuroendocrine factors are known to influence ion transport
      rates of these organs. Injection of micromolar doses of CAPA (an insect
      neuropeptide) have been previously demonstrated to improve Drosophila cold
      tolerance, but the mechanisms through which it impacts chill tolerance are
      unclear, and low doses of CAPA have been previously demonstrated to cause anti
      diuresis in insects, including dipterans. Here, we provide evidence that low
      (femtomolar) and high (micromolar) doses of CAPA impair and improve chill
      tolerance, respectively, via two different effects on Malpighian tubule ion and
      water transport. While low doses of CAPA are anti-diuretic, reduce tubule K+
      clearance rates and reduce chill tolerance, high doses facilitate K+ clearance
      from the haemolymph and increase chill tolerance. By quantifying CAPA peptide
      levels in the central nervous system, we estimated the maximum achievable
      hormonal titres of CAPA and found further evidence that CAPA may function as an
      anti-diuretic hormone in Drosophila melanogaster We provide the first evidence of
      a neuropeptide that can negatively affect cold tolerance in an insect and further
      evidence of CAPA functioning as an anti-diuretic peptide in this ubiquitous
      insect model.

PMID- 30104305
TI  - Multiple optic gland signaling pathways implicated in octopus maternal behaviors
      and death.
AB  - Post-reproductive life in the female octopus is characterized by an extreme
      pattern of maternal care: the mother cares for her clutch of eggs without feeding
      until her death. These maternal behaviors are eradicated if the optic glands, the
      octopus analog of the vertebrate pituitary gland, are removed from brooding
      females. Despite the optic gland's importance in regulating maternal behavior,
      the molecular features underlying optic gland function are unknown. Here, we
      identify major signaling systems of the Octopus bimaculoides optic gland. Through
      behavioral analyses and transcriptome sequencing, we report that the optic gland
      undergoes remarkable molecular changes that coincide with transitions between
      behavioral stages. These include the dramatic upregulation and downregulation of
      catecholamine, steroid, insulin and feeding peptide pathways. Transcriptome
      analyses in other tissues demonstrate that these molecular changes are not
      generalized markers of senescence, but instead, specific features of the optic
      glands. Our study expands the classic optic gland-pituitary gland analogy and
      more specifically, it indicates that, rather than a single 'self-destruct'
      hormone, the maternal optic glands employ multiple pathways as systemic hormonal
      signals of behavioral regulation.

PMID- 30104308
TI  - Validity and reliability of a medical record review method identifying
      transitional patient safety incidents in merged primary and secondary care
      patients' records.
AB  - OBJECTIVE: Inadequate information transfer during transitions in healthcare is a
      major patient safety issue. Aim of this study was to pilot a review of medical
      records to identify transitional safety incidents (TSIs) for use in a large
      intervention study and assess its reliability and validity. DESIGN: A
      retrospective medical record review study. SETTINGS AND PARTICIPANTS: Combined
      primary and secondary care medical records of 301 patients who had visited their
      general practitioner and the University Medical Center Utrecht, the Netherlands,
      in 2013 were randomly selected. Six trained reviewers assessed these medical
      records for presence of TSIs. OUTCOMES: To assess inter-rater reliability, 10% of
      medical records were independently reviewed twice. To assess validity, the
      identified TSIs were compared with a reference standard of three objectively
      identifiable TSIs. RESULTS: The reviewers identified TSIs in 52 (17.3%) of all
      transitional medical records. Variation between reviewers was high (range: 3-28
      per 50 medical records). Positive agreement for finding a TSI between reviewers
      was 0%, negative agreement 80% and the Cohen's kappa -0.15. The reviewers
      identified 43 (22%) of 194 objectively identifiable TSIs. CONCLUSION: The
      reliability of our measurement tool for identifying TSIs in transitional medical
      record performed by clinicians was low. Although the TSIs that were identified by
      clinicians were valid, they missed 80% of them. Restructuring the record review
      procedure is necessary.

PMID- 30104307
TI  - Cost-effectiveness of habit-based advice for weight control versus usual care in
      general practice in the Ten Top Tips (10TT) trial: economic evaluation based on a
      randomised controlled trial.
AB  - OBJECTIVE: Ten Top Tips (10TT) is a primary care-led behavioural intervention
      which aims to help adults reduce and manage their weight by following 10 weight
      loss tips. The intervention promotes habit formation to encourage long-term
      behavioural changes. The aim of this study was to estimate the cost-effectiveness
      of 10TT in general practice from the perspective of the UK National Health
      Service. DESIGN: An economic evaluation was conducted alongside an individually
      randomised controlled trial. SETTING: 14 general practitioner practices in
      England. PARTICIPANTS: All patients were aged >=18 years, with body mass index
      >=30 kg/m2. A total of 537 patients were recruited; 270 received the usual care
      offered by their practices and 267 received the 10TT intervention. OUTCOMES
      MEASURES: Health service use and quality-adjusted life years (QALYs) were
      measured over 2 years. Analysis was conducted in terms of incremental net
      monetary benefits (NMBs), using non-parametric bootstrapping and multiple
      imputation. RESULTS: Over a 2-year time horizon, the mean costs and QALYs per
      patient in the 10TT group were L1889 (95% CI L1522 to L2566) and 1.51 (95% CI
      1.44 to 1.58). The mean costs and QALYs for usual care were L1925 (95% CI L1599
      to L2251) and 1.51 (95% CI 1.45 to 1.57), respectively. This generated a mean
      cost difference of -L36 (95% CI -L512 to L441) and a mean QALY difference of
      0.001 (95% CI -0.080 to 0.082). The incremental NMB for 10TT versus usual care
      was L49 (95% CI -L1709 to L1800) at a maximum willingness to pay for a QALY of
      L20 000. 10TT had a 52% probability of being cost-effective at this threshold.
      CONCLUSIONS: Costs and QALYs for 10TT were not significantly different from usual
      care and therefore 10TT is as cost-effective as usual care. There was no evidence
      to recommend nor advice against offering 10TT to obese patients in general
      practices based on cost-effectiveness considerations. TRIAL REGISTRATION NUMBER:
      ISRCTN16347068; Post-results.

PMID- 30104310
TI  - Impact of sharing electronic health records with patients on the quality and
      safety of care: a systematic review and narrative synthesis protocol.
AB  - INTRODUCTION: Providing patients with access to electronic health records (EHRs)
      has emerged as a promising solution to improve quality of care and safety. As the
      efforts to develop and implement EHR-based data sharing platforms mature and
      scale up worldwide, there is a need to evaluate the impact of these interventions
      and to weigh their relative risks and benefits, in order to inform evidence-based
      health policies. The aim of this work is to systematically characterise and
      appraise the demonstrated benefits and risks of sharing EHR with patients, by
      mapping them across the six domains of quality of care of the Institute of
      Medicine (IOM) analytical framework (ie, patient-centredness, effectiveness,
      efficiency, timeliness, equity and safety). METHODS AND ANALYSIS: CINAHL,
      Cochrane, Embase, HMIC, Medline/PubMed and PsycINFO databases will be searched
      from January 1997 to August 2017. Primary outcomes will include measures related
      with the six domains of quality of care of the IOM analytical framework. The
      quality of the studies will be assessed using the Cochrane Risk of Bias Tool, the
      ROBINS-I Tool and the Drummond's checklist. A narrative synthesis will be
      conducted for all included studies. Subgroup analysis will be performed by domain
      of quality of care domain and by time scale (ie, short-term, medium-term or long
      term impact). The body of evidence will be summarised in a Summary of Findings
      table and its strength assessed according to the GRADE criteria. ETHICS AND
      DISSEMINATION: This review does not require ethical approval as it will summarise
      published studies with non-identifiable data. This protocol complies with the
      Preferred Reporting Items for Systematic Review and Meta-Analyses Protocols
      guidelines. Findings will be disseminated widely through peer-reviewed
      publication and conference presentations, and patient partners will be included
      in summarising the research findings into lay summaries and reports. PROSPERO
      REGISTRATION NUMBER: CRD42017070092.

PMID- 30104311
TI  - Retirement, job satisfaction and attitudes towards mandatory accreditation: a
      Danish survey study in general practice.
AB  - OBJECTIVES: This study aims to analyse the associations between general
      practitioner (GP) retirement, job satisfaction and attitudes towards a mandatory
      accreditation scheme. External interventions such as mandatory accreditation
      schemes may be perceived negatively by GPs, causing early retirement from
      practice. In Denmark, almost half of the GPs had negative attitudes prior to the
      implementation of a mandatory accreditation scheme, constituting a possible risk
      of early practice retirement. SETTING: In January 2015 all 3,404 Danish GPs were
      invited to participate in a survey on attitudes towards a forthcoming mandatory
      accreditation programme. PARTICIPANTS: 1,906 GPs (56%) answered the
      questionnaire. In total, 391 (11%) retired from practice in the following period
      from 1 January 2015 to 31 January 2017. Of these, 193 GPs (49%) answered the
      questionnaire. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was GP
      retirement. Labour union data on practice retirement were linked with data from
      the questionnaire survey on job satisfaction and attitudes prior to
      implementation of mandatory accreditation. Logistic regression analyses were used
      to determine the associations between practice retirement and job satisfaction
      and attitudes towards accreditation. RESULTS: Practice retirement was associated
      with job dissatisfaction (OR: 2.5, 95% CI 1.6 to 3.7). Retirement was not
      associated with any of the other surveyed attitudinal variables. Retirement rate
      was relatively high in the accreditation start-up period. CONCLUSION: Practice
      retirement was associated with job dissatisfaction but not to a priori attitudes
      towards an upcoming mandatory accreditation programme. However, the retirement
      rate was relatively high in the start-up period of the accreditation programme.
      Future research should evaluate the effects of external interventions on preterm
      retirement from general practice. TRIAL REGISTRATION NUMBER: NCT02762240.

PMID- 30104309
TI  - Effect of 6 months hybrid closed-loop insulin delivery in young people with type
      1 diabetes: a randomised controlled trial protocol.
AB  - INTRODUCTION: Automated insulin delivery (also known as closed loop, or
      artificial pancreas) has shown potential to improve glycaemic control and quality
      of life in people with type 1 diabetes (T1D). Automated insulin delivery devices
      incorporate an insulin pump with continuous glucose monitoring(CGM) and an
      algorithm, and adjust insulin in real time. This study aims to establish the
      safety and efficacy of a hybrid closed-loop (HCL) system in a long-term
      outpatient trial in people with T1D aged 12 -<25 years of age, and compare
      outcomes with standard therapy for T1D as used in the contemporary community.
      METHODS AND ANALYSIS: This is an open-label, multicentre, 6-month, randomised
      controlled home trial to test the MiniMed Medtronic 670G system (HCL) in people
      with T1D aged 12 -<25 years, and compare it to standard care (multiple daily
      injections or continuous subcutaneous insulin infusion (CSII), with or without
      CGM). Following a run-in period including diabetes and carbohydrate counting
      education, dosage optimisation and baseline glucose control data collection,
      participants are randomised to either HCL or to continue on their current
      treatment regimen. The primary aim of the study is to compare the proportion of
      time spent in target sensor glucose range (3.9-10.0 mmol/L) on HCL versus
      standard therapy. Secondary aims include a range of glucose control parameters,
      psychosocial measures, health economic measures, biomarker status,
      user/technology interactions and healthcare professional expectations. Analysis
      will be intention to treat. A study in adults with an aligned design is being
      conducted in parallel to this trial. ETHICS AND DISSEMINATION: Ethics committee
      permissions were gained from respective institutional review boards. The findings
      of the study will provide high-quality evidence on the role of HCL in clinical
      practice.

PMID- 30104312
TI  - Impact of missing individual patient data on 18 meta-analyses of randomised
      trials in oncology: Gustave Roussy experience.
AB  - OBJECTIVE: To compare the characteristics, quality and treatment effects of
      randomised clinical trials (RCTs) by individual patient data (IPD) availability,
      in trials eligible for 18 IPD meta-analyses (MA). DESIGN: Trial characteristics,
      risk of bias (RoB) and hazard ratio (HR) for overall survival were extracted from
      IPD-MA publications and/or RCTs publications. Data for the RoB assessment were
      extracted for a subset of 73 RCTs. Two investigators blinded to whether IPD was
      available or not evaluated the RoB for these trials. Treatment effects were
      compared using ratios of global HRs (RHRs) of IPD-unavailable trials and IPD
      available trials. RHR were pooled using a fixed-effect model. DATA SOURCES: We
      examined the IPD availability for each trial eligible for each IPD-MA; when the
      IPD was not available for a trial, we used information from published sources.
      ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We selected all published IPD-MAs
      conducted at Gustave Roussy and the RCTs eligible for each. RESULTS: 349 RCTs (73
      018 patients) from 18 MAs were eligible: 60 RCTs (5890 patients) had unavailable
      IPD and 289 RCTs (67 128 patients) had available IPD. The main reason for IPD
      unavailability was data loss by investigators. IPD-unavailable trials were
      smaller (p<0.001), more often monocentric (p<0.001) and non-international
      (p=0.0004) than IPD-available trials. Geographical areas differed (p=0.054)
      between IPD-unavailable IPD-available trials. RoB was higher in IPD-unavailable
      RCTs for random sequence generation (p=0.007) and allocation concealment
      (p=0.006). The HR and 95% confidence interval (CI) for overall survival were
      extractable from publications in 23/60 IPD-unavailable trials included in 10
      different MAs. Treatment effects were significantly greater for IPD-unavailable
      trials compared with IPD-available trials (RHR=0.86 (95% CI 0.75 to 0.98)).
      CONCLUSIONS: IPD-unavailable RCTs were significantly different from IPD-available
      RCTs in terms of trial characteristics and were at greater RoB. IPD-unavailable
      RCTs had a significantly greater treatment effect.

PMID- 30104313
TI  - Association of socioeconomic factors and the risk for unintentional injuries
      among children in Japan: a cross-sectional study.
AB  - OBJECTIVES: While Japan has socioeconomic issues, such as income inequality,
      little is known about the association between socioeconomic factors and the risk
      of unintentional childhood injuries. The purpose of the study was to evaluate the
      influence of socioeconomic factors on the risk for unintentional injuries among
      preschool children in Japan. DESIGN: Cross-sectional study using data from a web
      based questionnaire survey. SETTING: Japan (January 2015). PARTICIPANTS: 1000
      households with preschool children under 6 years of age. OUTCOME MEASURES:
      Multivariate logistic regression was performed to analyse the influence of
      socioeconomic factors on the incidence of unintentional injuries. RESULTS:
      Overall, 976 households were eligible for the analysis, with 201 households
      reporting unintentional injuries. The incidence rates for unintentional injury
      were estimated to be constant across all strata constructed using combinations of
      socioeconomic factors. The multivariate logistic regression analysis showed no
      significant differences in socioeconomic factors between households that reported
      unintentional injuries and those that did not. CONCLUSION: The findings of our
      study demonstrated that unintentional injuries among preschool children occurred
      at approximately fixed rates, independent of socioeconomic factors. Accordingly,
      prevention strategies for unintentional injuries that concern socioeconomic
      disadvantages should be avoided in Japan.

PMID- 30104314
TI  - Validation of the ICH score in patients with spontaneous intracerebral
      haemorrhage admitted to the intensive care unit in Southern Spain.
AB  - OBJECTIVE: Validation of the intracerebral haemorrhage (ICH) score in patients
      with a diagnosis of spontaneous ICH admitted to the intensive care unit (ICU).
      METHODS: A multicentre cohort study was conducted in all consecutive patients
      with ICH admitted to the ICUs of three hospitals with a neurosurgery department
      between 2009 and 2012 in Andalusia, Spain. Data collected included ICH, Glasgow
      Coma Scale (GCS) and Acute Physiology and Chronic Health Evaluation II (APACHE
      II) scores. Demographic data, location and volume of haematoma and 30-day
      mortality rate were also collated. RESULTS: A total of 336 patients were
      included. 105 of whom underwent surgery. Median (IQR) age: 62 (50-70) years.
      APACHE-II: 21(15-26) points, GCS: 7 (4-11) points, ICH score: 2 (2-3) points.
      11.1% presented with bilateral mydriasis on admission (mortality rate=100%).
      Intraventricular haemorrhage was observed in 58.9% of patients. In-hospital
      mortality was 54.17% while the APACHE-II predicted mortality was 57.22% with a
      standardised mortality ratio (SMR) of 0.95 (95% CI 0.81 to 1.09) and a Hosmer
      Lemenshow test value (H) of 3.62 (no significant statistical difference, n.s.).
      30-day mortality was 52.38% compared with the ICH score predicted mortality of
      48.79%, SMR: 1.07 (95% CI 0.91 to 1.23), n.s. Mortality was higher than predicted
      at the lowest scores and lower than predicted in the more severe patients,
      (H=55.89, p<0.001), Gruppo Italiano per la Valutazione degli Interventi in
      Terapia Intensiva calibration belt (p<0.001). The area under a receiver operating
      characteristic (ROC) curve was 0.74 (95% CI 0.69 to 0.79). CONCLUSIONS: ICH score
      shows an acceptable discrimination as a tool to predict mortality rates in
      patients with spontaneous ICH admitted to the ICU, but its calibration is
      suboptimal.

PMID- 30104315
TI  - A call for Applied Knowledge and Lived Interdisciplinarity in the medical care of
      depressed employees: a cross-sectional survey with German occupational physicians
      and psychotherapists.
AB  - OBJECTIVES: To identify approaches for an effective patient-centred care of
      depressed employees, we investigated occupational physicians' (OPs) and
      psychotherapists' (PTs) knowledge about job stressors on the development of
      depression, application of this knowledge, interdisciplinary cooperation and
      perceived barriers. STUDY DESIGN: A cross-sectional online survey. PARTICIPANTS:
      OPs (163; 48.5% male) and PTs (69; 43.5% male) providing complete data on the
      survey out of 257 OPs and 112 PTs who started the survey. There have been 458
      (OPs) and 821 (PTs) initial clicks. METHODS: Main outcome measures were the
      importance ratings of specific job stressors, the frequency of asking patients
      about those stressors, the need for interdisciplinary cooperation, as well as
      perceived barriers for cooperation. We performed multivariate analysis of
      variance, intraclass correlation coefficients (ICCs) and Spearman's rank-order
      correlations. RESULTS: The achieved response rate for OPs was 56.1% and for PTs
      13.6%. Both disciplines agreed on the importance of job stressors regarding
      depression (ICC=0.90; 95% CI: 0.54 to 0.98), but both ranked these factors
      differently from the current state of research. As to knowledge application, OPs
      showed positive associations between the importance of job stressors and the
      frequency of asking employees about them (eg, job insecurity (rs=0.20, p=0.005))
      and PTs for social stressors (eg, interpersonal conflicts (rs=0.38, p=0.001)).
      OPs (mean=3.41) reported a higher necessity of interdisciplinary cooperation than
      PTs (mean=3.17; F(1,230)=7.02, p=0.009). Furthermore, cooperation was reported as
      difficult to implement. PTs perceived barriers (eg, time restriction) as more
      hindering (mean=3.2) than OPs (mean=2.8; F(1,171)=8.16, p=0.005). CONCLUSIONS:
      Both disciplines are aware of the relevance of job stressors as risk factors for
      depression, but should be encouraged to ask employees more frequently about them.
      The need for interdisciplinary cooperation and possible barriers are discussed.
      It is crucial to emphasise the meaning of sufficient cooperation, since closing
      this gap for improving patient-centred care especially for employees suffering
      from depression is necessary.

PMID- 30104316
TI  - Sugar and energy content of carbonated sugar-sweetened beverages in Haidian
      District, Beijing: a cross-sectional study.
AB  - OBJECTIVE: The consumption of carbonated sugar-sweetened beverages (CSSBs) is
      associated with a range of health problems, but little is known about the sugar
      and energy content of CSSBs in China. The study aimed to investigate the sugar
      and energy content of CSSBs in Beijing, China. STUDY DESIGN: We carried out a
      cross-sectional survey in 15 different supermarkets from July to October 2017 in
      Haidian District, Beijing. METHODS: The product packaging and nutrient labels of
      CSSBs were recorded by a snapshot in time to obtain company name, product name,
      serving size, and nutrient content, that is, carbohydrate, sugar and energy. For
      CSSB labels not showing sugar content, we used carbohydrate content as
      substitute. The sugar and energy content of CSSBs within each type of flavour
      were compared using Kruskal-Wallis test. The sugar content within the recommended
      levels was described using frequency. We also compared the sugar and energy
      content of top 5 CSSBs in terms of sales among three countries (China, UK and
      USA). RESULTS: A total of 93 CSSB products were found. The median sugar content
      was 9.3 (IQR: 5.7-11.2) g/100 mL, and the energy content was 38 (IQR: 23-46)
      kcal/100 mL. There were 79 products labelled 'Red' (high) per serving based on
      the criteria set in the UK (>11.25 g/100 mL). We found 62.4% of CSSBs had sugar
      content per serving that exceeds the daily free sugar intake for adults (25 g)
      recommended by the WHO. Some of the branded products sold in China had higher
      sugar content when they were compared with those in Western countries.
      CONCLUSIONS: CSSBs in Beijing, China have high sugar and energy content.
      Reduction in sugar content and serving size of CSSBs and taxation policy on
      beverages will be beneficial in reducing sugar intake in China.

PMID- 30104317
TI  - Predicting intrapartum fetal compromise at term using the cerebroplacental ratio
      and placental growth factor levels (PROMISE) study: randomised controlled trial
      protocol.
AB  - INTRODUCTION: Intrapartum complications are a major contributor to adverse
      perinatal outcomes, including stillbirth, hypoxic-ischaemic brain injury and
      subsequent longer term disability. In many cases, hypoxia develops as a gradual
      process due to the inability of the fetus to tolerate the stress of parturition
      suggesting reduced fetoplacental reserve before labour commences. The fetal
      cerebroplacental ratio (CPR) is an independent predictor of intrapartum fetal
      compromise, poor acid base status at birth and of neonatal unit admission at
      term. Similarly, circulating maternal levels of placental growth factor (PlGF)
      are lower in pregnancies complicated by placental dysfunction. This paper
      outlines the protocol for the PROMISE Study, which aims to determine if the
      introduction of a prelabour screening test for intrapartum fetal compromise
      combining the CPR and maternal PlGF level results in a reduction of adverse
      perinatal outcomes. METHODS AND ANALYSIS: This is a single-site, non-blinded,
      individual patient randomised controlled trial of a screening test performed at
      term, combining the fetal CPR and maternal serum PlGF. Women with a singleton,
      non-anomalous pregnancy will be recruited after 34 weeks' gestation and
      randomised to either receive the screening test or not. Screened pregnancies
      determined to be at risk will be recommended induction of labour. Demographic,
      obstetric history and antenatal data will be collected at enrolment, and
      perinatal outcomes will be recorded after delivery. Relative risks and 95% CIs
      will be reported for the primary outcome. Regression techniques will be used to
      examine the influence of prognostic factors on the primary and secondary
      outcomes. ETHICS AND DISSEMINATION: This study has been reviewed and approved by
      the Mater Human Research Ethics Committee (Reference: HREC EC00332) and will
      follow the principles of Good Clinical Practice. The study results will be
      disseminated at national and international conferences and published in peer
      reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12616001009404; Pre-results.

PMID- 30104318
TI  - Sex and gender differences in caregiving burden experienced by family caregivers
      of persons with dementia: a systematic review protocol.
AB  - INTRODUCTION: While much is known about caregiving burden and its consequences on
      both caregivers and care recipients, reports on the sex and gender differences
      that may be present among family caregivers of persons with dementia (PWD) are
      lacking. Attention to and a synthesis of these sex and gender distinctions have
      direct implications on the planning and development of health services for this
      population. The current protocol outlines a strategy for a systematic review of
      the current evidence to identify and synthesise sex and gender distinctions in
      caregiving burden experienced by family caregivers of PWD. METHODS AND ANALYSIS:
      A comprehensive search strategy for studies that examine the sex and gender
      differences in caregiving impacts and experiences has been developed in
      collaboration with an information specialist at a university. All peer-reviewed
      English language studies on adult family caregivers of PWD, published from
      January 2007 to September 2017, found through Medline, Embase, PsycINFO,
      Cumulative Index to Nursing and Allied Health Literature and bibliographies of
      identified articles, will be considered eligible. Study quality will be assessed
      using the Critical Appraisal Skills Programme checklists. ETHICS AND
      DISSEMINATION: As the first systematic review of its kind that focus on sex and
      gender differences in caregiving burden, findings will be relevant for healthcare
      practitioners and researchers who can better prescribe and develop interventions
      and technologies to better address the specific challenges and burden experienced
      by male and female family caregivers of PWD. Moreover, given that more than half
      of family caregivers are females; these sex and gender differences will also be
      pertinent to policy-makers when evaluating and planning of our healthcare systems
      to better meet the needs of this population. TRIAL REGISTRATION NUMBER:
      CRD42018070032.

PMID- 30104319
TI  - Does pictorial health information improve health behaviours and other outcomes? A
      systematic review protocol.
AB  - INTRODUCTION: Most health information is verbal or written, yet words alone may
      not be the most effective way to communicate health information. Lower health
      literacy is prevalent in the US and is linked to limited understanding of one's
      medical condition and treatment. Pictures increase comprehension, recall,
      adherence and attention in health settings. This is called pictorial superiority.
      No systematic review has examined the impact of pictorial health information
      among patients and consumers, including those with lower health literacy. METHODS
      AND ANALYSIS: This systematic review and meta-analysis will assess the
      characteristics and effectiveness of pictorial health information on patient and
      consumer health behaviours and outcomes, as well as differentially among
      individuals of lower literacy/lower health literacy. We will conduct a systematic
      search across selected databases, as well as grey literature, from inception
      until June 2018. We will include randomised controlled trials in all languages
      with all types of participants that assess the effect of pictorial health
      information on patients' and consumers' health behaviours and outcomes. Two
      independent reviewers will conduct the primary screening of articles and data
      extraction for the selected articles with a third individual available to resolve
      conflicts. We will assess the quality of all included studies using the Cochrane
      risk of bias tool. We will combine all selected studies and do a test of
      heterogeneity. If there is sufficient homogeneity, we will pool studies into a
      meta-analysis. Independent of the heterogeneity of included studies, we will also
      conduct a narrative synthesis. ETHICS AND DISSEMINATION: No ethics approval is
      required. The results will be published in a peer-reviewed journal and presented
      at relevant conferences. PROSPERO REGISTRATION NUMBER: CRD42018084743.

PMID- 30104320
TI  - Association between subjective tinnitus and cognitive performance: protocol for
      systematic review and meta-analysis.
AB  - INTRODUCTION: Subjective tinnitus is very common and has a number of comorbid
      associations including depression, sleep disturbance and concentration
      difficulties. Concentration difficulties may be observable in people with
      tinnitus through poorer behavioural performance in tasks thought to measure
      specific cognitive domains such as attention and memory (ie, cognitive
      performance). Several reviews have discussed the association between tinnitus and
      cognition; however, none to date have investigated the association between
      tinnitus and cognitive performance through meta-analysis with reference to an
      established theoretical taxonomy. Furthermore, there has been little overlap
      between sets of studies that have been included in previous reviews, potentially
      contributing to the typically mixed findings that are reported. METHODS AND
      ANALYSIS: This systematic review aims to comprehensively review the literature
      using an established theoretical taxonomy and quantitatively synthesise relevant
      data to determine associations between subjective tinnitus and cognitive
      performance. Methods are reported according to Preferred Reporting Items for
      Systematic Reviews and Meta-Analyses Protocols. All study designs will be
      eligible for inclusion with no date restrictions on searches. Studies eligible
      for inclusion must contain adult participants (>=18 years) with subjective
      tinnitus and a behavioural measure of cognitive performance. Meta-analysis will
      be reported via correlation for the association between tinnitus and cognitive
      performance. ETHICS AND DISSEMINATION: No ethical issues are foreseen. Findings
      will be reported in a student thesis, at national and international , ear, nose
      and throat/audiology conferences and by peer-reviewed publication. PROSPERO
      REGISTRATION NUMBER: CRD42018085528.

PMID- 30104321
TI  - Protocol for a mixed-methods evaluation of a massive open online course on real
      world evidence.
AB  - INTRODUCTION: Increasing number of Massive Open Online Courses (MOOCs) are being
      used to train learners at scale in various healthcare-related skills. However,
      many challenges in course delivery require further understanding, for example,
      factors exploring the reasons for high MOOC dropout rates, recorded low social
      interaction between learners and the lack of understanding of the impact of a
      course facilitators' presence in course engagement. There is a need to generate
      further evidence to explore these detriments to MOOC course delivery to enable
      enhanced course learning design. The proposed mixed-methods evaluation of the
      MOOC was determined based on the MOOC's aims and objectives and the
      methodological approaches used to evaluate this type of a course. The MOOC
      evaluation will help appraise the effectiveness of the MOOC in delivering its
      intended objectives. This protocol aims to describe the design of a study
      evaluating learners knowledge, skills and attitudes in a MOOCs about data science
      for healthcare. METHODS AND ANALYSIS: Study participants will be recruited from
      learners who have registered for the MOOC. On registration, learners will be
      given an opportunity to opt into the study and complete informed consent.
      Following completion of the course, study participants will be contacted to
      complete semistructured interviews. Interviews will be transcribed and coded
      using thematic analysis, with data analysed using two evaluation models: (1) the
      reach, effectiveness, adoption, implementation, maintenance framework and the (2)
      Kirkpatrick model drawing data from pre and post-course surveys and post-MOOC
      semi-structured interviews. The primary goal of the evaluation is to appraise
      participants' knowledge, skills and attitude after taking the MOOC. ETHICS AND
      DISSEMINATION: Ethics approval for this study was obtained from Imperial College
      London through the Education Ethics Review Process (EERP) (EERP1617-030). A
      summary of the research findings will be reported through a peer-reviewed journal
      and will be presented at an international conference.

PMID- 30104322
TI  - Induced Pluripotent Stem Cell-Derived Podocyte-Like Cells as Models for Assessing
      Mechanisms Underlying Heritable Disease Phenotype: Initial Studies Using Two
      Alport Syndrome Patient Lines Indicate Impaired Potassium Channel Activity.
AB  - Renal podocyte survival depends upon the dynamic regulation of a complex cell
      architecture that links the glomerular basement membrane to integrins, ion
      channels, and receptors. Alport syndrome is a heritable chronic kidney disease
      where mutations in alpha3, alpha4, or alpha5 collagen genes promote podocyte
      death. In rodent models of renal failure, activation of the calcium-sensing
      receptor (CaSR) can protect podocytes from stress-related death. In this study,
      we assessed CaSR function in podocyte-like cells derived from induced-pluripotent
      stem cells from two patients with Alport Syndrome (AS1 & AS2) and a renal disease
      free individual [normal human mesangial cell (NHMC)], as well as a human
      immortalized podocyte-like (HIP) cell line. Extracellular calcium elicited
      concentration-dependent elevations of intracellular calcium in all podocyte-like
      cells. NHMC and HIP, but not AS1 or AS2 podocyte-like cells, also showed acute
      reductions in intracellular calcium prior to elevation. In NHMC podocyte-like
      cells this acute reduction was blocked by the large-conductance potassium channel
      (KCNMA1) inhibitors iberiotoxin (10 nM) and tetraethylammonium (5 mM), as well as
      the focal adhesion kinase inhibitor PF562271 (N-methyl-N-(3-((2-(2-oxo-2,3
      dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino)-methyl)
      pyridin-2-yl)-methanesulfonamide, 10 nM). Quantitative polymerase chain reaction
      (qPCR) and immunolabeling showed the presence of KCNMA1 transcript and protein in
      all podocyte-like cells tested. Cultivation of AS1 podocytes on decellularized
      plates of NHMC podocyte-like cells partially restored acute reductions in
      intracellular calcium in response to extracellular calcium. We conclude that the
      AS patient-derived podocyte-like cells used in this study showed dysfunctional
      integrin signaling and potassium channel function, which may contribute to
      podocyte death seen in Alport syndrome.

PMID- 30104323
TI  - Beta-3 Adrenoceptor Signaling Pathways in Urothelial and Smooth Muscle Cells in
      the Presence of Succinate.
AB  - Succinate, an intermediate metabolite of the Krebs cycle, can alter the
      metabolomics response to certain drugs and controls an array of molecular
      responses in the urothelium through activation of its receptor, G-protein coupled
      receptor 91 (GPR91). Mirabegron, a beta3-adrenergic receptor (beta3-AR) agonist
      used to treat overactive bladder syndrome (OAB), increases intracellular cAMP in
      the detrusor smooth muscle cells (SMC), leading to relaxation. We have previously
      shown that succinate inhibits forskolin-stimulated cAMP production in urothelium.
      To determine whether succinate interferes with mirabegron-mediated bladder
      relaxation, we examined their individual and synergistic effect in urothelial
      cell and SMC signaling. We first confirmed beta3-AR involvement in the mirabegron
      response by quantifying receptor abundance by immunoblotting in cultured
      urothelial cells and SMC and cellular localization by immunohistochemistry in rat
      bladder tissue. Mirabegron increased cAMP levels in SMC but not in urothelial
      cells, an increase that was inhibited by succinate, suggesting that it impairs
      cAMP-mediated bladder relaxation by mirabegron. Succinate and mirabegron
      increased inducible nitric oxide synthesis and nitric oxide secretion only in
      urothelial cells, suggesting that its release can indirectly induces SMC
      relaxation. Succinate exposure decreased the expression of beta3-AR protein in
      whole bladder in vivo and in SMC in vitro, indicating that this metabolite may
      lead to impaired pharmacodynamics of the bladder. Together, our results
      demonstrate that increased levels of succinate in settings of metabolic stress
      (e.g., the metabolic syndrome) may lead to impaired mirabegron and beta3-AR
      interaction, inhibition of cAMP production, and ultimately requiring mirabegron
      dose adjustment for its treatment of OAB related to these conditions.

PMID- 30104324
TI  - Fifteen minute consultation: Fever in children being treated for cancer.
AB  - Fever is a common symptom in children receiving treatment for cancer. Clinicians
      and families are most concerned about febrile neutropenia, though non-neutropenic
      fever often causes more challenging treatment dilemmas. This article provides a
      structured approach to the initial assessment, examination, investigation and
      risk assessment of children with fever during treatment for childhood cancer. Non
      neutropenic fever in children with cancer is not well researched. There are no
      systematic reviews of its management and no National Institute for Health and
      Care Excellence (NICE) (or other international) guidance about what to do.
      Features to consider when managing non-neutropenic fever are discussed. Febrile
      neutropenia, meanwhile, is an oncological emergency and requires management using
      standard sepsis principles including administration of broad-spectrum
      antibiotics. Relevant NICE guidance provides a clear structure for treatment.
      Ongoing management depends on the response to initial treatment.

PMID- 30104325
TI  - How to use... Imaging for umbilical venous catheter placement.

PMID- 30104326
TI  - Early detection of multiple myeloma in primary care using blood tests: a case
      control study in primary care.
AB  - BACKGROUND: Multiple myeloma is a haematological cancer characterised by numerous
      non-specific symptoms leading to diagnostic delay in a large proportion of
      patients. AIM: To identify which blood tests are useful in suggesting or
      excluding a diagnosis of myeloma. DESIGN AND SETTING: A matched case-control
      study set in UK primary care using routinely collected data from the Clinical
      Practice Research Datalink. METHOD: Symptom prevalence and blood tests were
      analysed up to 5 years before diagnosis in 2703 cases and 12 157 matched
      controls. Likelihood ratios (LR) were used to classify tests or their
      combinations as useful rule-in tests (LR+ = >=5), or rule-out tests (LR- =
      <=0.2). RESULTS: Raised plasma viscosity (PV) had an LR+ = 2.0, 95% confidence
      interval [CI] = 1.7 to 2.3; erythrocyte sedimentation rate (ESR) 1.9, 95% CI =
      1.7 to 2.0; and C-reactive protein (CRP) 1.2, 95% CI = 1.1 to 1.4. A normal
      haemoglobin had an LR- = 0.42, 95% CI = 0.39 to 0.45; calcium LR- = 0.81, 95% CI
      = 0.78 to 0.83; and creatinine LR- = 0.80, 95% CI = 0.77 to 0.83. The test
      combination with the lowest LR- was all normal haemoglobin with calcium and PV,
      which had an LR- = 0.06, 95% CI = 0.02 to 0.18, though the LR- for normal
      haemoglobin and PV together was 0.12 (95% CI = 0.07 to 0.23). CONCLUSION: Plasma
      viscosity and ESR are better for both ruling in and ruling out the disease
      compared with C-reactive protein. A combination of a normal ESR or PV and normal
      haemoglobin is a simple rule-out approach for patients currently being tested in
      primary care.

PMID- 30104327
TI  - Effectiveness of reminder strategies on cancer screening adherence: a randomised
      controlled trial.
AB  - BACKGROUND: Few randomised controlled trials (RCTs) have evaluated the different
      recalling approaches for enhancing adherence to faecal immunochemical test (FIT)
      based screening. AIM: The authors evaluated the effectiveness of two
      telecommunication strategies on improving adherence to yearly FIT screening.
      DESIGN AND SETTING: A randomised, parallel group trial was performed in a primary
      care screening practice. METHOD: The authors recruited 629 asymptomatic
      individuals aged 40-70 years with a negative FIT in 2015 to a population-based
      screening programme. On participation, they were invited to repeat their second
      round of FIT in 2016, 12 months after the first test. Each participant was
      randomly assigned to either interactive telephone reminder (n = 207), short
      message service reminder (SMS, n = 212), or control, where no additional
      interventions were delivered after the findings of their first FIT was
      communicated to the participants (n = 210). Reminders in the intervention groups
      were delivered 1 month before subjects' expected return. Additional telephone
      reminders were delivered 2 months after the expected return date to all subjects
      who defaulted specimen return. The outcomes included rates of FIT collection and
      specimen return up to 6 months after their expected return. RESULTS: At 6 months,
      the cumulative FIT collection rate was 95.1%, 90.4%, and 86.5%, respectively, for
      the telephone, SMS, and control groups (P = 0.010). The corresponding specimen
      return rate was 94.1%, 90.0%, and 86.0% (P = 0.022). When compared with the
      control, only subjects in the telephone group were significantly more likely to
      collect FIT tubes (adjusted odds ratio [AOR] 3.18, 95% confidence interval [CI] =
      1.50 to 6.75, P = 0.003) and return completed specimens (AOR = 2.73, 95% CI =
      1.35 to 5.53, P = 0.005). CONCLUSION: Interactive telephone reminders are
      effective at securing previously screened subjects to repeat screening 1 year
      after a negative finding.

PMID- 30104329
TI  - GP-delivered brief weight loss interventions: a cohort study of patient responses
      and subsequent actions, using conversation analysis in UK primary care.
AB  - BACKGROUND: Guidelines encourage GPs to make brief opportunistic interventions to
      support weight loss. However, GPs fear that starting these discussions will lead
      to lengthy consultations. Recognising that patients are committed to take action
      could allow GPs to shorten brief interventions. AIM: To examine which patient
      responses indicated commitment to action, and the time saved if these had been
      recognised and the consultation closed sooner. DESIGN AND SETTING: A mixed-method
      cohort study of UK primary care patients participating in a trial of
      opportunistic weight management interventions. METHOD: Conversation analysis was
      applied to 226 consultation audiorecordings to identify types of responses from
      patients that indicated that an offer of referral to weight management was well
      received. Odds ratios (OR) were calculated to examine associations between
      response types and likelihood of weight management programme attendance. RESULTS:
      Affirmative responses, for example 'yes', displayed no conversational evidence
      that the referral was well received and showed no association with attendance:
      'yes' (OR 1.2, 95% confidence interval [CI] = 0.37 to 3.95, P = 0.97). However,
      'oh'-prefaced responses and marked positive responses, for example 'lovely',
      showed conversational evidence of enthusiasm and were associated with higher odds
      of commercial weight management service attendance. Recognising these could have
      saved doctors a mean of 31 seconds per consultation. CONCLUSION: When doctors
      make brief opportunistic interventions that incorporate the offer of help, 'oh'
      prefaced or marked positive responses indicate enthusiastic acceptance of the
      offer and a higher likelihood of take-up. Recognising these responses and moving
      swiftly to facilitate patient action would shorten the brief intervention in many
      cases.

PMID- 30104330
TI  - Hypertension care: sharing the burden with pharmacists.

PMID- 30104328
TI  - Direct access cancer testing in primary care: a systematic review of use and
      clinical outcomes.
AB  - BACKGROUND: Direct access (DA) testing allows GPs to refer patients for
      investigation without consulting a specialist. The aim is to reduce waiting time
      for investigations and unnecessary appointments, enabling treatment to begin
      without delay. AIM: To establish the proportion of patients diagnosed with cancer
      and other diseases through DA testing, time to diagnosis, and suitability of DA
      investigations. DESIGN AND SETTING: Systematic review assessing the effectiveness
      of GP DA testing in adults. METHOD: MEDLINE, Embase, and the Cochrane Library
      were searched. Where possible, study data were pooled and analysed
      quantitatively. Where this was not possible, the data are presented narratively.
      RESULTS: The authors identified 60 papers that met pre-specified inclusion
      criteria. Most studies were carried out in the UK and were judged to be of poor
      quality. The authors found no significant difference in the pooled cancer
      conversion rate between GP DA referrals and patients who first consulted a
      specialist for any test, except gastroscopy. There were also no significant
      differences in the proportions of patients receiving any non-cancer diagnosis.
      Referrals for testing were deemed appropriate in 66.4% of those coming from GPs,
      and in 80.9% of those from consultants; this difference was not significant. The
      time from referral to testing was significantly shorter for patients referred for
      DA tests. Patient and GP satisfaction with DA testing was consistently high.
      CONCLUSION: GP DA testing performs as well as, and on some measures better than,
      consultant triaged testing on measures of disease detection, appropriateness of
      referrals, interval from referral to testing, and patient and GP satisfaction.

PMID- 30104332
TI  - Margaret McCartney: Reading makes us better doctors.

PMID- 30104331
TI  - Stakeholders' views on identifying patients in primary care at risk of dying: a
      qualitative descriptive study using focus groups and interviews.
AB  - BACKGROUND: Strategies have been developed for use in primary care to identify
      patients at risk of declining health and dying, yet little is known about the
      perceptions of doing so or the broader implications and impacts. AIM: To explore
      the acceptability and implications of using a primary care-based electronic
      medical record algorithm to help providers identify patients in their practice at
      risk of declining health and dying. DESIGN AND SETTING: Qualitative descriptive
      study in Ontario and Nova Scotia, Canada. METHOD: Six focus groups were
      conducted, supplemented by one-on-one interviews, with 29 healthcare providers,
      managers, and policymakers in primary care, palliative care, and geriatric care.
      Participants were purposively sampled to achieve maximal variation. Data were
      analysed using a constant comparative approach. RESULTS: Six themes were
      prevalent across the dataset: early identification is aligned with the values,
      aims, and positioning of primary care; providers have concerns about what to do
      after identification; how we communicate about the end of life requires change;
      early identification and subsequent conversations require an integrated team
      approach; for patients, early identification will have implications beyond
      medical care; and a public health approach is needed to optimise early
      identification and its impact. CONCLUSION: Stakeholders were much more concerned
      with how primary care providers would navigate the post-identification period
      than with early identification itself. Implications of early identification
      include the need for a team-based approach to identification and to engage
      broader communities to ensure people live and die well post-identification.

PMID- 30104334
TI  - Improved Survival Seen for Some with Pancreatic Cancer.
AB  - In two pancreatic cancer trials-the randomized phase III PRODIGE 24/CCTG PA.6 and
      PREOPANC-1 trials-researchers found that experimental drug regimens for patients
      with resectable adenocarcinomas increased overall survival or showed a trend in
      that direction. The findings could prompt changes in clinical practice for these
      patients.

PMID- 30104333
TI  - A Digital RNA Signature of Circulating Tumor Cells Predicting Early Therapeutic
      Response in Localized and Metastatic Breast Cancer.
AB  - The multiplicity of new therapies for breast cancer presents a challenge for
      treatment selection. We describe a 17-gene digital signature of breast
      circulating tumor cell (CTC)-derived transcripts enriched from blood, enabling
      high-sensitivity early monitoring of response. In a prospective cohort of
      localized breast cancer, an elevated CTC score after three cycles of neoadjuvant
      therapy is associated with residual disease at surgery (P = 0.047). In a second
      prospective cohort with metastatic breast cancer, baseline CTC score correlates
      with overall survival (P = 0.02), as does persistent CTC signal after 4 weeks of
      treatment (P = 0.01). In the subset with estrogen receptor (ER)-positive disease,
      failure to suppress ER signaling within CTCs after 3 weeks of endocrine therapy
      predicts early progression (P = 0.008). Drug-refractory ER signaling within CTCs
      overlaps partially with presence of ESR1 mutations, pointing to diverse
      mechanisms of acquired endocrine drug resistance. Thus, CTC-derived digital RNA
      signatures enable noninvasive pharmacodynamic measurements to inform therapy in
      breast cancer.Significance: Digital analysis of RNA from CTCs interrogates
      treatment responses of both localized and metastatic breast cancer. Quantifying
      CTC-derived ER signaling during treatment identifies patients failing to respond
      to ER suppression despite having functional ESR1. Thus, noninvasive scoring of
      CTC-RNA signatures may help guide therapeutic choices in localized and advanced
      breast cancer. Cancer Discov; 8(10); 1286-99. (c)2018 AACR. This article is
      highlighted in the In This Issue feature, p. 1195.

PMID- 30104337
TI  - Influence of vmPFC on dmPFC Predicts Valence-Guided Belief Formation.
AB  - When updating beliefs about their future prospects, people tend to disregard bad
      news. By combining fMRI with computational and dynamic causal modeling, we
      identified neurocircuitry mechanisms underlying this optimism bias to test for
      valence-guided belief formation. In each trial of the fMRI task, participants (n
      = 24, 10 male) estimated the base rate (eBR) and their risks of experiencing
      negative future events, were confronted with the actual BR, and finally had the
      opportunity to update their initial self-related risk estimate. We demonstrated
      an optimism bias by revealing greater belief updates in response to good over bad
      news (i.e., learning that the actual BR is lower or higher than expected) while
      controlling for confounds (estimation error and personal relevance of the new
      information). Updating was favorable when the final belief about risks improved
      (or at least did not worsen) relative to the initial risk estimate. This valence
      of updating was encoded by the ventromedial prefrontal cortex (vmPFC) associated
      with the valuation of rewards. Within the updating circuit, the vmPFC filtered
      the incoming signal in a valence-dependent manner and influenced the dorsomedial
      prefrontal cortex (dmPFC). Both the valence-encoding activity in the vmPFC and
      its influence on the dmPFC predicted individual magnitudes of the optimism bias.
      Our results indicate that updating was biased by the motivation to maximize
      desirable beliefs, mediated by the influence of the valuation system on further
      cognitive processing. Therefore, although it provides the very basis for human
      reasoning, belief formation is essentially distorted to promote desired
      conclusions.SIGNIFICANCE STATEMENT The question of whether human reasoning is
      biased by desires and goals is crucial for everyday social, professional, and
      economic decisions. How much our belief formation is influenced by what we want
      to believe is, however, still debated. Our study confirms that belief updates are
      indeed optimistically biased. Critically, the bias depends on the recruitment of
      the brain valuation system and the influence of this system on neural regions
      involved in reasoning. These neurocircuit interactions support the notion that
      the motivation to maximize pleasant beliefs reinforces those cognitive processes
      that are most likely to yield the desired conclusion.

PMID- 30104336
TI  - Language Exposure Relates to Structural Neural Connectivity in Childhood.
AB  - Neuroscience research has elucidated broad relationships between socioeconomic
      status (SES) and young children's brain structure, but there is little
      mechanistic knowledge about specific environmental factors that are associated
      with specific variation in brain structure. One environmental factor, early
      language exposure, predicts children's linguistic and cognitive skills and later
      academic achievement, but how language exposure relates to neuroanatomy is
      unknown. By measuring the real-world language exposure of young children (ages 4
      6 years, 27 male/13 female), we confirmed the preregistered hypothesis that
      greater adult-child conversational experience, independent of SES and the sheer
      amount of adult speech, is related to stronger, more coherent white matter
      connectivity in the left arcuate and superior longitudinal fasciculi on average,
      and specifically near their anterior termination at Broca's area in left inferior
      frontal cortex. Fractional anisotropy of significant tract subregions mediated
      the relationship between conversational turns and children's language skills and
      indicated a neuroanatomical mechanism underlying the SES "language gap." Post hoc
      whole-brain analyses revealed that language exposure was not related to any other
      white matter tracts, indicating the specificity of this relationship. Results
      suggest that the development of dorsal language tracts is environmentally
      influenced, specifically by early, dialogic interaction. Furthermore, these
      findings raise the possibility that early intervention programs aiming to
      ameliorate disadvantages in development due to family SES may focus on increasing
      children's conversational exposure to capitalize on the early neural plasticity
      underlying cognitive development.SIGNIFICANCE STATEMENT Over the last decade,
      cognitive neuroscience has highlighted the detrimental impact of disadvantaged
      backgrounds on young children's brain structure. However, to intervene
      effectively, we must know which proximal aspects of the environmental aspects are
      most strongly related to neural development. The present study finds that young
      children's real-world language exposure, and specifically the amount of adult
      child conversation, correlates with the strength of connectivity in the left
      hemisphere white matter pathway connecting two canonical language regions,
      independent of socioeconomic status and the sheer volume of adult speech. These
      findings suggest that early intervention programs aiming to close the achievement
      gap may focus on increasing children's conversational exposure to capitalize on
      the early neural plasticity underlying cognitive development.

PMID- 30104335
TI  - Posterior Parietal Cortex Dysfunction Is Central to Working Memory Storage and
      Broad Cognitive Deficits in Schizophrenia.
AB  - PFC dysfunction is widely believed to underlie working memory (WM) deficits in
      people with schizophrenia (PSZ), but few studies have focused on measures of WM
      storage devoid of manipulation. Research in neurotypical individuals has shown
      that storage capacity is more closely related to posterior parietal cortex (PPC)
      than PFC, suggesting that reductions in WM storage capacity in schizophrenia that
      are associated with broad cognitive deficits may be related to neural activity in
      PPC. In the present human neuroimaging study, 37 PSZ and 37 matched healthy
      control subjects of either sex completed a change detection task with varying set
      sizes while undergoing fMRI. The task was designed to emphasize WM storage with
      minimal top-down control demands. Whole-brain analysis identified areas in which
      BOLD activity covaried with the number of items maintained in WM (K), as derived
      from task performance at a given set size. Across groups, K values independent of
      set size predicted BOLD activity in PPC, including superior and inferior parietal
      lobules and intraparietal sulcus, and middle occipital gyrus. Whole-brain
      interaction analysis found significantly less K-dependent signal modulation in
      PSZ than healthy control subjects in left PPC, a phenomenon that could not be
      explained by a narrower K value range. The slope between K and PPC activation
      statistically accounted for 43.4% of the between-group differences in broad
      cognitive function. These results indicate that PPC dysfunction is central to WM
      storage deficits in PSZ and may play a key role in the broad cognitive deficits
      associated with schizophrenia.SIGNIFICANCE STATEMENT People with schizophrenia
      exhibit cognitive deficits across a wide range of tasks. Explaining these
      impairments in terms of a small number of core deficits with clearly defined
      neural correlates would advance the understanding of the disorder and promote
      treatment development. We show that a substantial portion of broad cognitive
      deficits in schizophrenia can be explained by a failure to flexibly modulate
      posterior parietal cortex activity as a function of the amount of information
      currently stored in working memory. Working memory deficits have long been
      considered central to schizophrenia-related cognitive deficits, but the focus has
      been on paradigms involving some form of top-down control rather than pure
      storage of information, which may have unduly narrowed the focus on prefrontal
      dysfunction.

PMID- 30104339
TI  - Motion Extrapolation for Eye Movements Predicts Perceived Motion-Induced Position
      Shifts.
AB  - Transmission delays in the nervous system pose challenges for the accurate
      localization of moving objects as the brain must rely on outdated information to
      determine their position in space. Acting effectively in the present requires
      that the brain compensates not only for the time lost in the transmission and
      processing of sensory information, but also for the expected time that will be
      spent preparing and executing motor programs. Failure to account for these delays
      will result in the mislocalization and mistargeting of moving objects. In the
      visuomotor system, where sensory and motor processes are tightly coupled, this
      predicts that the perceived position of an object should be related to the
      latency of saccadic eye movements aimed at it. Here we use the flash-grab effect,
      a mislocalization of briefly flashed stimuli in the direction of a reversing
      moving background, to induce shifts of perceived visual position in human
      observers (male and female). We find a linear relationship between saccade
      latency and perceived position shift, challenging the classic dissociation
      between "vision for action" and "vision for perception" for tasks of this kind
      and showing that oculomotor position representations are either shared with or
      tightly coupled to perceptual position representations. Altogether, we show that
      the visual system uses both the spatial and temporal characteristics of an
      upcoming saccade to localize visual objects for both action and
      perception.SIGNIFICANCE STATEMENT Accurately localizing moving objects is a
      computational challenge for the brain due to the inevitable delays that result
      from neural transmission. To solve this, the brain might implement motion
      extrapolation, predicting where an object ought to be at the present moment.
      Here, we use the flash-grab effect to induce perceptual position shifts and show
      that the latency of imminent saccades predicts the perceived position of the
      objects they target. This counterintuitive finding is important because it not
      only shows that motion extrapolation mechanisms indeed work to reduce the
      behavioral impact of neural transmission delays in the human brain, but also that
      these mechanisms are closely matched in the perceptual and oculomotor systems.

PMID- 30104338
TI  - Altered Gamma Oscillations during Motor Control in Children with Autism Spectrum
      Disorder.
AB  - Autism is hypothesized to result in a cortical excitatory and inhibitory
      imbalance driven by inhibitory interneuron dysfunction, which is associated with
      the generation of gamma oscillations. On the other hand, impaired motor control
      has been widely reported in autism. However, no study has focused on the gamma
      oscillations during motor control in autism. In the present study, we
      investigated the motor-related gamma oscillations in autism using
      magnetoencephalography. Magnetoencephalographic signals were recorded from 14
      right-handed human children with autism (5 female), aged 5-7 years, and age- and
      IQ-matched 15 typically developing children during a motor task using their right
      index finger. Consistent with previous studies, the autism group showed a
      significantly longer button response time and reduced amplitude of motor-evoked
      magnetic fields. We observed that the autism group exhibited a low peak frequency
      of motor-related gamma oscillations from the contralateral primary motor cortex,
      and these were associated with the severity of autism symptoms. The autism group
      showed a reduced power of motor-related gamma oscillations in the bilateral
      primary motor cortex. A linear discriminant analysis using the button response
      time and gamma oscillations showed a high classification performance (86.2%
      accuracy). The alterations of the gamma oscillations in autism might reflect the
      cortical excitatory and inhibitory imbalance. Our findings provide an important
      clue into the behavioral and neurophysiological alterations in autism and a
      potential biomarker for autism.SIGNIFICANCE STATEMENT Currently, the diagnosis of
      autism has been based on behavioral assessments, and a crucial issue in the
      diagnosis of autism is to identify objective and quantifiable clinical
      biomarkers. A key hypothesis of the neurophysiology of autism is an excitatory
      and inhibitory imbalance in the brain, which is associated with the generation of
      gamma oscillations. On the other hand, motor deficits have also been widely
      reported in autism. This is the first study to demonstrate low motor performance
      and altered motor-related gamma oscillations in autism, reflecting a brain
      excitatory and inhibitory imbalance. Using these behavioral and
      neurophysiological parameters, we classified autism and control group with good
      accuracy. This work provides important information on behavioral and
      neurophysiological alterations in patients with autism.

PMID- 30104341
TI  - alpha-Neurexins Together with alpha2delta-1 Auxiliary Subunits Regulate Ca2+
      Influx through Cav2.1 Channels.
AB  - Action potential-evoked neurotransmitter release is impaired in knock-out neurons
      lacking synaptic cell-adhesion molecules alpha-neurexins (alphaNrxns), the
      extracellularly longer variants of the three vertebrate Nrxn genes. Ca2+ influx
      through presynaptic high-voltage gated calcium channels like the ubiquitous P/Q
      type (CaV2.1) triggers release of fusion-ready vesicles at many boutons.
      alpha2delta Auxiliary subunits regulate trafficking and kinetic properties of
      CaV2.1 pore-forming subunits but it has remained unclear if this involves
      alphaNrxns. Using live cell imaging with Ca2+ indicators, we report here that the
      total presynaptic Ca2+ influx in primary hippocampal neurons of alphaNrxn triple
      knock-out mice of both sexes is reduced and involved lower CaV2.1-mediated
      transients. This defect is accompanied by lower vesicle release, reduced synaptic
      abundance of CaV2.1 pore-forming subunits, and elevated surface mobility of
      alpha2delta-1 on axons. Overexpression of Nrxn1alpha in alphaNrxn triple knock
      out neurons is sufficient to restore normal presynaptic Ca2+ influx and synaptic
      vesicle release. Moreover, coexpression of Nrxn1alpha together with alpha2delta-1
      subunits facilitates Ca2+ influx further but causes little augmentation together
      with a different subunit, alpha2delta-3, suggesting remarkable specificity.
      Expression of defined recombinant CaV2.1 channels in heterologous cells validates
      and extends the findings from neurons. Whole-cell patch-clamp recordings show
      that Nrxn1alpha in combination with alpha2delta-1, but not with alpha2delta-3,
      facilitates Ca2+ currents of recombinant CaV2.1 without altering channel
      kinetics. These results suggest that presynaptic Nrxn1alpha acts as a positive
      regulator of Ca2+ influx through CaV2.1 channels containing alpha2delta-1
      subunits. We propose that this regulation represents an important way for neurons
      to adjust synaptic strength.SIGNIFICANCE STATEMENT Synaptic transmission between
      neurons depends on the fusion of neurotransmitter-filled vesicles with the
      presynaptic membrane, which subsequently activates postsynaptic receptors. Influx
      of calcium ions into the presynaptic terminal is the key step to trigger vesicle
      release and involves different subtypes of voltage-gated calcium channels. We
      study the regulation of calcium channels by neurexins, a family of synaptic cell
      adhesion molecules that are essential for many synapse properties. Using optical
      measurements of calcium influx in cultured neurons and electrophysiological
      recordings of calcium currents from recombinant channels, we show that a major
      neurexin variant facilitates calcium influx through P/Q-type channels by
      interacting with their alpha2delta-1 auxiliary subunits. These results propose a
      novel way how neurons can modulate the strength of distinct synapses.

PMID- 30104342
TI  - Ultrafast Cortical Gain Adaptation in the Human Brain by Trial-To-Trial Changes
      of Associative Strength in Fear Learning.
AB  - In fear conditioning, more efficient sensory processing of a stimulus (the
      conditioned stimulus, CS) that has acquired motivational relevance by being
      paired with an aversive event (the unconditioned stimulus, US) has been
      associated with increased cortical gain in early sensory brain areas (Miskovic
      and Keil, 2012). Further, this sensory gain modulation related to short-term
      plasticity changes occurs independently of aware cognitive anticipation of the
      aversive US, pointing toward implicit learning mechanisms (Moratti and Keil,
      2009). However, it is unknown how quickly the implicit learning of CS-US
      associations results in the adaptation of cortical gain. Here, using steady-state
      visually evoked fields derived from human Magnetoencephalography (MEG) recordings
      in two experiments (N = 33, 17 females and 16 males), we show that stimulus
      driven neuromagnetic oscillatory activity increases and decreases quickly as a
      function of associative strength within three or four trials, as predicted by a
      computationally implemented Rescorla-Wagner model with the highest learning rate.
      These ultrafast cortical gain adaptations are restricted to early visual cortex
      using a delay fear conditioning procedure. Short interval (500 ms) trace
      conditioning resulted in the same ultrafast activity modulations by associative
      strength, but in a complex occipito-parieto-temporo-frontal network. Granger
      causal analysis revealed that reverberating top-down and bottom-up influences
      between anterior and posterior brain regions during trace conditioning
      characterized this network. Critically, in both delay and trace conditioning,
      ultrafast cortical gain modulations as a function of associative strength
      occurred independently of conscious US anticipation.SIGNIFICANCE STATEMENT In
      ever-changing environments, learned associations between a cue and an aversive
      consequence must change under new stimulus-consequence contingencies to be
      adaptive. What predicts potential dangers now might be meaningless in the next
      situation. Predictive cues are prioritized, as reflected by increased sensory
      cortex activity for these cues. However, this modulation also must adapt to
      altered stimulus-consequence contingencies. Here, we show that human visual
      cortex activity can be modulated quickly according to ultrafast contingency
      changes within a few learning trials. This finding extends to frontal brain
      regions when the cue and the aversive event are separated in time. Critically,
      this ultrafast updating process occurs orthogonally to aware aversive outcome
      anticipation and therefore relies on unconscious implicit learning mechanisms.

PMID- 30104340
TI  - Morphological and Biophysical Determinants of the Intracellular and Extracellular
      Waveforms in Nigral Dopaminergic Neurons: A Computational Study.
AB  - Action potentials (APs) in nigral dopaminergic neurons often exhibit two separate
      components: the first reflecting spike initiation in the dendritically located
      axon initial segment (AIS) and the second the subsequent dendro-somatic spike.
      These components are separated by a notch in the ascending phase of the somatic
      extracellular waveform and in the temporal derivative of the somatic
      intracellular waveform. Still, considerable variability exists in the presence
      and magnitude of the notch across neurons. To systematically address the
      contribution of AIS, dendritic and somatic compartments to shaping the two
      component APs, we modeled APs of previously in vivo electrophysiologically
      characterized and 3D-reconstructed male mouse and rat dopaminergic neurons. A
      parsimonious two-domain model, with high (AIS) and lower (dendro-somatic) Na+
      conductance, reproduced the notch in the temporal derivatives, but not in the
      extracellular APs, regardless of morphology. The notch was only revealed when
      somatic active currents were reduced, constraining the model to three domains.
      Thus, an initial AIS spike is followed by an actively generated spike by the axon
      bearing dendrite (ABD), in turn followed mostly passively by the soma. The
      transition from being a source compartment for the AIS spike to a source
      compartment for the ABD spike satisfactorily explains the extracellular somatic
      notch. Larger AISs and thinner ABD (but not soma-to-AIS distance) accentuate the
      AIS component. We conclude that variability in AIS size and ABD caliber explains
      variability in AP extracellular waveform and separation of AIS and dendro-somatic
      components, given the presence of at least three functional domains with distinct
      excitability characteristics.SIGNIFICANCE STATEMENT Midbrain dopamine neurons
      make an important contribution to circuits mediating motivation and movement.
      Understanding the basic rules that govern the electrical activity of single
      dopaminergic neurons is therefore essential to reveal how they ultimately
      contribute to movement and motivation as well as what goes wrong in associated
      disorders. Our computational study focuses on the generation and propagation of
      action potentials and shows that different morphologies and excitability
      characteristics of the cell body, dendrites and proximal axon can explain the
      diversity of action potentials shapes in this population. These compartments
      likely make differential contributions both to normal dopaminergic signaling and
      could potentially underlie pathological dopaminergic signaling implicated in
      addiction, schizophrenia, Parkinson's disease, and other disorders.

PMID- 30104344
TI  - S-Nitrosylation of Divalent Metal Transporter 1 Enhances Iron Uptake to Mediate
      Loss of Dopaminergic Neurons and Motoric Deficit.
AB  - Elevated iron deposition has been reported in Parkinson's disease (PD). However,
      the route of iron uptake leading to high deposition in the substantia nigra is
      unresolved. Here, we show a mechanism in enhanced Fe2+ uptake via S-nitrosylation
      of divalent metal transporter 1 (DMT1). While DMT1 could be S-nitrosylated by
      exogenous nitric oxide donors, in human PD brains, endogenously S-nitrosylated
      DMT1 was detected in postmortem substantia nigra. Patch-clamp
      electrophysiological recordings and iron uptake assays confirmed increased Mn2+
      or Fe2+ uptake through S-nitrosylated DMT1. We identified two major S
      nitrosylation sites, C23 and C540, by mass spectrometry, and DMT1 C23A or C540A
      substitutions abolished nitric oxide (NO)-mediated DMT1 current increase. To
      evaluate in vivo significance, lipopolysaccharide (LPS) was stereotaxically
      injected into the substantia nigra of female and male mice to induce inflammation
      and production of NO. The intranigral LPS injection resulted in corresponding
      increase in Fe2+ deposition, JNK activation, dopaminergic neuronal loss and
      deficit in motoric activity, and these were rescued by the NO synthase inhibitor
      l-NAME or by the DMT1-selective blocker ebselen. Lentiviral knockdown of DMT1
      abolished LPS-induced dopaminergic neuron loss.SIGNIFICANCE STATEMENT
      Neuroinflammation and high cytoplasmic Fe2+ levels have been implicated in the
      initiation and progression of neurodegenerative diseases. Here, we report the
      unexpected enhancement of the functional activity of transmembrane divalent metal
      transporter 1 (DMT1) by S-nitrosylation. We demonstrated that S-nitrosylation
      increased DMT1-mediated Fe2+ uptake, and two cysteines were identified by mass
      spectrometry to be the sites for S-nitrosylation and for enhanced iron uptake.
      One conceptual advance is that while DMT1 activity could be increased by external
      acidification because the gating of the DMT1 transporter is proton motive, we
      discovered that DMT1 activity could also be enhanced by S-nitrosylation.
      Significantly, lipopolysaccharide-induced nitric oxide (NO)-mediated neuronal
      death in the substantia nigra could be ameliorated by using l-NAME, a NO synthase
      inhibitor, or by ebselen, a DMT1-selective blocker.

PMID- 30104345
TI  - Spectroscopic ruler for measuring active-site distortions based on Raman optical
      activity of a hydrogen out-of-plane vibration.
AB  - Photoactive yellow protein (PYP), from the phototrophic bacterium Halorhodospira
      halophila, is a small water-soluble photoreceptor protein and contains p-coumaric
      acid (pCA) as a chromophore. PYP has been an attractive model for studying the
      physical chemistry of protein active sites. Here, we explore how Raman optical
      activity (ROA) can be used to extract quantitative information on distortions of
      the pCA chromophore at the active site in PYP. We use 13C8-pCA to assign an
      intense signal at 826 cm-1 in the ROA spectrum of PYP to a hydrogen out-of-plane
      vibration of the ethylenic moiety of the chromophore. Quantum-chemical
      calculations based on density functional theory demonstrate that the sign of this
      ROA band reports the direction of the distortion in the dihedral angle about the
      ethylenic C=C bond, while its amplitude is proportional to the dihedral angle.
      These results document the ability of ROA to quantify structural deformations of
      a cofactor molecule embedded in a protein moiety.

PMID- 30104343
TI  - A Transient Developmental Window of Fast-Spiking Interneuron Dysfunction in a
      Mouse Model of Dravet Syndrome.
AB  - Dravet syndrome is a severe, childhood-onset epilepsy largely due to heterozygous
      loss-of-function mutation of the gene SCN1A, which encodes the type 1 neuronal
      voltage-gated sodium (Na+) channel alpha subunit Nav1.1. Prior studies in mouse
      models of Dravet syndrome (Scn1a+/- mice) indicate that, in cerebral cortex,
      Nav1.1 is predominantly expressed in GABAergic interneurons, in particular in
      parvalbumin-positive fast-spiking basket cell interneurons (PVINs). This has led
      to a model of Dravet syndrome pathogenesis in which Nav1.1 mutation leads to
      preferential dysfunction of interneurons, decreased synaptic inhibition,
      hyperexcitability, and epilepsy. However, such studies have been implemented at
      early developmental time points. Here, we performed electrophysiological
      recordings in acute brain slices prepared from male and female Scn1a+/- mice as
      well as age-matched wild-type littermate controls and found that, later in
      development, the excitability of PVINs had normalized. Analysis of action
      potential waveforms indirectly suggests a reorganization of axonal Na+ channels
      in PVINs from Scn1a+/- mice, a finding supported by immunohistochemical data
      showing elongation of the axon initial segment. Our results imply that transient
      impairment of action potential generation by PVINs may contribute to the initial
      appearance of epilepsy, but is not the mechanism of ongoing, chronic epilepsy in
      Dravet syndrome.SIGNIFICANCE STATEMENT Dravet syndrome is characterized by normal
      early development, temperature-sensitive seizures in infancy, progression to
      treatment-resistant epilepsy, developmental delay, autism, and sudden unexplained
      death due to mutation in SCN1A encoding the Na+ channel subunit Nav1.1. Prior
      work has revealed a preferential impact of Nav1.1 loss on the function of
      GABAergic inhibitory interneurons. However, such data derive exclusively from
      recordings of neurons in young Scn1a+/- mice. Here, we show that impaired action
      potential generation observed in parvalbumin-positive fast-spiking interneurons
      (PVINs) in Scn1a+/- mice during early development has normalized by postnatal day
      35. This work suggests that a transient impairment of PVINs contributes to
      epilepsy onset, but is not the mechanism of ongoing, chronic epilepsy in Dravet
      syndrome.

PMID- 30104346
TI  - Mre11 complex links sister chromatids to promote repair of a collapsed
      replication fork.
AB  - Collapsed replication forks, which are a major source of DNA double-strand breaks
      (DSBs), are repaired by sister chromatid recombination (SCR). The Mre11-Rad50
      Nbs1 (MRN) protein complex, assisted by CtIP/Sae2/Ctp1, initiates SCR by
      nucleolytically resecting the single-ended DSB (seDSB) at the collapsed fork. The
      molecular architecture of the MRN intercomplex, in which zinc hooks at the apices
      of long Rad50 coiled-coils connect two Mre112-Rad502 complexes, suggests that MRN
      also structurally assists SCR. Here, Rad50 ChIP assays in Schizosaccharomyces
      pombe show that MRN sequentially localizes with the seDSB and sister chromatid at
      a collapsed replication fork. Ctp1, which has multivalent DNA-binding and DNA
      bridging activities, has the same DNA interaction pattern. Provision of an
      intrachromosomal repair template alleviates the nonnucleolytic requirement for
      MRN to repair the broken fork. Mutations of zinc-coordinating cysteines in the
      Rad50 hook severely impair SCR. These data suggest that the MRN complex
      facilitates SCR by linking the seDSB and sister chromatid.

PMID- 30104347
TI  - Thioredoxin-like2/2-Cys peroxiredoxin redox cascade supports oxidative thiol
      modulation in chloroplasts.
AB  - Thiol-based redox regulation is central to adjusting chloroplast functions under
      varying light conditions. A redox cascade via the ferredoxin-thioredoxin
      reductase (FTR)/thioredoxin (Trx) pathway has been well recognized to mediate the
      light-responsive reductive control of target proteins; however, the molecular
      basis for reoxidizing its targets in the dark remains unidentified. Here, we
      report a mechanism of oxidative thiol modulation in chloroplasts. We
      biochemically characterized a chloroplast stroma-localized atypical Trx from
      Arabidopsis, designated as Trx-like2 (TrxL2). TrxL2 had redox-active properties
      with an unusually less negative redox potential. By an affinity chromatography
      based method, TrxL2 was shown to interact with a range of chloroplast redox
      regulated proteins. The direct discrimination of thiol status indicated that
      TrxL2 can efficiently oxidize, but not reduce, these proteins. A notable
      exception was found in 2-Cys peroxiredoxin (2CP); TrxL2 was able to reduce 2CP
      with high efficiency. We achieved a complete in vitro reconstitution of the
      TrxL2/2CP redox cascade for oxidizing redox-regulated proteins and draining
      reducing power to hydrogen peroxide (H2O2). We further addressed the
      physiological relevance of this system by analyzing protein-oxidation dynamics.
      In Arabidopsis plants, a decreased level of 2CP led to the impairment of the
      reoxidation of redox-regulated proteins during light-dark transitions. A delayed
      response of protein reoxidation was concomitant with the prolonged accumulation
      of reducing power in TrxL2. These results suggest an in vivo function of the
      TrxL2/2CP redox cascade for driving oxidative thiol modulation in chloroplasts.

PMID- 30104349
TI  - Small room for compromise between oil palm cultivation and primate conservation
      in Africa.
AB  - Despite growing awareness about its detrimental effects on tropical biodiversity,
      land conversion to oil palm continues to increase rapidly as a consequence of
      global demand, profitability, and the income opportunity it offers to producing
      countries. Although most industrial oil palm plantations are located in Southeast
      Asia, it is argued that much of their future expansion will occur in Africa. We
      assessed how this could affect the continent's primates by combining information
      on oil palm suitability and current land use with primate distribution,
      diversity, and vulnerability. We also quantified the potential impact of large
      scale oil palm cultivation on primates in terms of range loss under different
      expansion scenarios taking into account future demand, oil palm suitability,
      human accessibility, carbon stock, and primate vulnerability. We found a high
      overlap between areas of high oil palm suitability and areas of high conservation
      priority for primates. Overall, we found only a few small areas where oil palm
      could be cultivated in Africa with a low impact on primates (3.3 Mha, including
      all areas suitable for oil palm). These results warn that, consistent with the
      dramatic effects of palm oil cultivation on biodiversity in Southeast Asia,
      reconciling a large-scale development of oil palm in Africa with primate
      conservation will be a great challenge.

PMID- 30104348
TI  - Altered conformational landscape and dimerization dependency underpins the
      activation of EGFR by alphaC-beta4 loop insertion mutations.
AB  - Mutational activation of epidermal growth factor receptor (EGFR) in human cancers
      involves both point mutations and complex mutations (insertions and deletions).
      In particular, short in-frame insertion mutations within a conserved alphaC-beta4
      loop in the EGFR kinase domain are frequently observed in tumor samples and
      patients harboring these mutations are insensitive to first-generation EGFR
      inhibitors. Despite the prevalence and clinical relevance of insertion mutations,
      the mechanisms by which these mutations regulate EGFR activity and contribute to
      drug sensitivity are poorly understood. Using cell-based mutation screening, we
      find that the precise location, length, and sequence of the inserted segment are
      critical for ligand-independent EGFR activation and downstream signaling. We
      identify three insertion mutations (N771_P772insN, D770_N771insG, and D770>GY)
      that activate EGFR in a unique way by relying more on the "acceptor" interface
      for kinase activation. Our drug inhibition studies indicate that these activating
      insertion mutations respond more favorably to osimertinib, a recently Food and
      Drug Administration-approved EGFR inhibitor for T790M-positive patients with lung
      cancer. Molecular dynamics simulations and umbrella sampling of WT and mutant
      EGFR suggest a model in which activating insertion mutations increase catalytic
      activity by relieving key autoinhibitory interactions associated with alphaC
      helix movement and by lowering the transition free energy ([Formula: see text])
      between active and inactive states. Our studies also identify a transition state
      sampled by activating insertion mutations that can be exploited in the design of
      mutant-selective EGFR inhibitors.

PMID- 30104350
TI  - Effects of environmental stressors on daily governance.
AB  - Human workers ensure the functioning of governments around the world. The
      efficacy of human workers, in turn, is linked to the climatic conditions they
      face. Here we show that the same weather that amplifies human health hazards also
      reduces street-level government workers' oversight of these hazards. To do so, we
      employ US data from over 70 million regulatory police stops between 2000 and
      2017, from over 500,000 fatal vehicular crashes between 2001 and 2015, and from
      nearly 13 million food safety violations across over 4 million inspections
      between 2012 and 2016. We find that cold and hot temperatures increase fatal
      crash risk and incidence of food safety violations while also decreasing police
      stops and food safety inspections. Added precipitation increases fatal crash risk
      while also decreasing police stops. We examine downscaled general circulation
      model output to highlight the possible day-to-day governance impacts of climate
      change by 2050 and 2099. Future warming may augment regulatory oversight during
      cooler seasons. During hotter seasons, however, warming may diminish regulatory
      oversight while simultaneously amplifying the hazards government workers are
      tasked with overseeing.

PMID- 30104353
TI  - Controlling fracture cascades through twisting and quenching.
AB  - Fracture fundamentally limits the structural stability of macroscopic and
      microscopic matter, from beams and bones to microtubules and nanotubes. Despite
      substantial recent experimental and theoretical progress, fracture control
      continues to present profound practical and theoretical challenges. While bending
      induced fracture of elongated rod-like objects has been intensely studied, the
      effects of twist and quench dynamics have yet to be explored systematically.
      Here, we show how twist and quench protocols may be used to control such fracture
      processes, by revisiting Feynman's observation that dry spaghetti typically
      breaks into three or more pieces when exposed to large pure bending stresses.
      Combining theory and experiment, we demonstrate controlled binary fracture of
      brittle elastic rods for two distinct protocols based on twisting and
      nonadiabatic quenching. Our experimental data for twist-controlled fracture agree
      quantitatively with a theoretically predicted phase diagram, and we establish
      asymptotic scaling relations for quenched fracture. Due to their general
      character, these results are expected to apply to torsional and kinetic fracture
      processes in a wide range of systems.

PMID- 30104352
TI  - Archaeogenomic evidence from the southwestern US points to a pre-Hispanic scarlet
      macaw breeding colony.
AB  - Hundreds of scarlet macaw (Ara macao cyanoptera) skeletons have been recovered
      from archaeological contexts in the southwestern United States and northwestern
      Mexico (SW/NW). The location of these skeletons, >1,000 km outside their
      Neotropical endemic range, has suggested a far-reaching pre-Hispanic acquisition
      network. Clear evidence for scarlet macaw breeding within this network is only
      known from the settlement of Paquime in NW dating between 1250 and 1450 CE.
      Although some scholars have speculated on the probable existence of earlier
      breeding centers in the SW/NW region, there has been no supporting evidence. In
      this study, we performed an ancient DNA analysis of scarlet macaws recovered from
      archaeological sites in Chaco Canyon and the contemporaneous Mimbres area of New
      Mexico. All samples were directly radiocarbon dated between 900 and 1200 CE. We
      reconstructed complete or near-complete mitochondrial genome sequences of 14
      scarlet macaws from five different sites. We observed remarkably low genetic
      diversity in this sample, consistent with breeding of a small founder population
      translocated outside their natural range. Phylogeographic comparisons of our
      ancient DNA mitogenomes with mitochondrial sequences from macaws collected during
      the last 200 years from their endemic Neotropical range identified genetic
      affinity between the ancient macaws and a single rare haplogroup (Haplo6)
      observed only among wild macaws in Mexico and northern Guatemala. Our results
      suggest that people at an undiscovered pre-Hispanic settlement dating between 900
      and 1200 CE managed a macaw breeding colony outside their endemic range and
      distributed these symbolically important birds through the SW.

PMID- 30104351
TI  - Phosphoinositides control the localization of HOPS subunit VPS41, which together
      with VPS33 mediates vacuole fusion in plants.
AB  - The vacuole is an essential organelle in plant cells, and its dynamic nature is
      important for plant growth and development. Homotypic membrane fusion is required
      for vacuole biogenesis, pollen germination, stomata opening, and gravity
      perception. Known components of the vacuole fusion machinery in eukaryotes
      include SNARE proteins, Rab GTPases, phosphoinositides, and the homotypic fusion
      and vacuolar protein sorting (HOPS) tethering complex. HOPS function is not well
      characterized in plants, but roles in embryogenesis and pollen tube elongation
      have been reported. Here, we show that Arabidopsis HOPS subunits VPS33 and VPS41
      accumulate in late endosomes and that VPS41, but not VPS33, accumulates in the
      tonoplast via a wortmannin-sensitive process. VPS41 and VPS33 proteins bind to
      liposomes, but this binding is inhibited by phosphatidylinosiltol-3-phosphate
      [PtdIns(3)P] and PtdIns(3,5)P2, which implicates a nonconserved mechanism for
      HOPS recruitment in plants. Inducible knockdown of VPS41 resulted in dramatic
      vacuole fragmentation phenotypes and demonstrated a critical role for HOPS in
      vacuole fusion. Furthermore, we provide evidence for genetic interactions between
      VPS41 and VTI11 SNARE that regulate vacuole fusion, and the requirement of a
      functional SNARE complex for normal VPS41 and VPS33 localization. Finally, we
      provide evidence to support VPS33 and SYP22 at the initial stage for HOPS-SNARE
      interactions, which is similar to other eukaryotes. These results highlight both
      conserved and specific mechanisms for HOPS recruitment and function during
      vacuole fusion in plants.

PMID- 30104355
TI  - Discovery of fissionogenic Cs and Ba capture five years after Oklo reactor
      shutdown.
AB  - Understanding the release and sequestration of specific radioactive signatures
      into the environment is of extreme importance for long-term nuclear waste storage
      and reactor accident mitigation. Recent accidents at the Fukushima and Chernobyl
      nuclear reactors released radioactive 137Cs and 134Cs into the environment, the
      former of which is still live today. We have studied the migration of fission
      products in the Oklo natural nuclear reactor using an isotope imaging capability,
      the NAval Ultra-Trace Isotope Laboratory's Universal Spectrometer (NAUTILUS) at
      the US Naval Research Laboratory. In Oklo reactor zone (RZ) 13, we have
      identified the most depleted natural U of any known material with a 235U/238U
      ratio of 0.3655 +/- 0.0007% (2sigma). This sample contains the most extreme
      natural burnup in 149Sm, 151Eu, 155Gd, and 157Gd, which demonstrates that it was
      sourced from the most active Oklo reactor region. We have discovered that
      fissionogenic Cs and Ba were captured by Ru metal/sulfide aggregates shortly
      following reactor shutdown. Isochrons from the Ru aggregates place their closure
      time at 4.98 +/- 0.56 y after the end of criticality. Most fissionogenic 135Ba
      and 137Ba in the Ru migrated and was incorporated as Cs over this period.
      Excesses in 134Ba in the Ru point to the burnup of 133Cs. Cesium and Ba were
      retained in the Ru despite local volcanic activity since the reactor shutdown and
      the high level of activity during reactor operation.

PMID- 30104354
TI  - Recycled ancient ghost carbonate in the Pitcairn mantle plume.
AB  - The extreme Sr, Nd, Hf, and Pb isotopic compositions found in Pitcairn Island
      basalts have been labeled enriched mantle 1 (EM1), characterizing them as one of
      the isotopic mantle end members. The EM1 origin has been vigorously debated for
      over 25 years, with interpretations ranging from delaminated subcontinental
      lithosphere, to recycled lower continental crust, to recycled oceanic crust
      carrying ancient pelagic sediments, all of which may potentially generate the
      requisite radiogenic isotopic composition. Here we find that delta26Mg ratios in
      Pitcairn EM1 basalts are significantly lower than in normal mantle and are the
      lowest values so far recorded in oceanic basalts. A global survey of Mg isotopic
      compositions of potentially recycled components shows that marine carbonates
      constitute the most common and typical reservoir invariably characterized by
      extremely low delta26Mg values. We therefore infer that the subnormal delta26Mg
      of the Pitcairn EM1 component originates from subducted marine carbonates. This,
      combined with previously published evidence showing exceptionally unradiogenic Pb
      as well as sulfur isotopes affected by mass-independent fractionation, suggests
      that the Pitcairn EM1 component is most likely derived from late Archean
      subducted carbonate-bearing sediments. However, the low Ca/Al ratios of Pitcairn
      lavas are inconsistent with experimental evidence showing high Ca/Al ratios in
      melts derived from carbonate-bearing mantle sources. We suggest that carbonate
      silicate reactions in the late Archean subducted sediments exhausted the
      carbonates, but the isotopically light magnesium of the carbonate was
      incorporated in the silicates, which then entered the lower mantle and ultimately
      became the Pitcairn plume source.

PMID- 30104356
TI  - Linguistic effect on speech perception observed at the brainstem.
AB  - Linguistic experience affects speech perception from early infancy, as previously
      evidenced by behavioral and brain measures. Current research focuses on whether
      linguistic effects on speech perception can be observed at an earlier stage in
      the neural processing of speech (i.e., auditory brainstem). Brainstem responses
      reflect rapid, automatic, and preattentive encoding of sounds. Positive
      experiential effects have been reported by examining the frequency-following
      response (FFR) component of the complex auditory brainstem response (cABR) in
      response to sustained high-energy periodic portions of speech sounds (vowels and
      lexical tones). The current study expands the existing literature by examining
      the cABR onset component in response to transient and low-energy portions of
      speech (consonants), employing simultaneous magnetoencephalography (MEG) in
      addition to electroencephalography (EEG), which provide complementary source
      information on cABR. Utilizing a cross-cultural design, we behaviorally measured
      perceptual responses to consonants in native Spanish- and English-speaking
      adults, in addition to cABR. Brain and behavioral relations were examined.
      Results replicated previous behavioral differences between language groups and
      further showed that individual consonant perception is strongly associated with
      EEG-cABR onset peak latency. MEG-cABR source analysis of the onset peaks
      complimented the EEG-cABR results by demonstrating subcortical sources for both
      peaks, with no group differences in peak locations. Current results demonstrate a
      brainstem-perception relation and show that the effects of linguistic experience
      on speech perception can be observed at the brainstem level.

PMID- 30104358
TI  - Chromatin structure and its chemical modifications regulate the ubiquitin ligase
      substrate selectivity of UHRF1.
AB  - Mitotic inheritance of DNA methylation patterns is facilitated by UHRF1, a DNA-
      and histone-binding E3 ubiquitin ligase that helps recruit the maintenance DNA
      methyltransferase DNMT1 to replicating chromatin. The DNA methylation maintenance
      function of UHRF1 is dependent on its ability to bind chromatin, where it
      facilitates monoubiquitination of histone H3 at lysines 18 and 23, a docking site
      for DNMT1. Because of technical limitations, this model of UHRF1-dependent DNA
      methylation inheritance has been constructed largely based on genetics and
      biochemical observations querying methylated DNA oligonucleotides, synthetic
      histone peptides, and heterogeneous chromatin extracted from cells. Here, we
      construct semisynthetic mononucleosomes harboring defined histone and DNA
      modifications and perform rigorous analysis of UHRF1 binding and enzymatic
      activity with these reagents. We show that multivalent engagement of nucleosomal
      linker DNA and dimethylated lysine 9 on histone H3 directs UHRF1 ubiquitin ligase
      activity toward histone substrates. Notably, we reveal a molecular switch,
      stimulated by recognition of hemimethylated DNA, which redirects UHRF1 ubiquitin
      ligase activity away from histones in favor of robust autoubiquitination. Our
      studies support a noncompetitive model for UHRF1 and DNMT1 chromatin recruitment
      to replicating chromatin and define a role for hemimethylated linker DNA as a
      regulator of UHRF1 ubiquitin ligase substrate selectivity.

PMID- 30104357
TI  - Strongly correlated perovskite lithium ion shuttles.
AB  - Solid-state ion shuttles are of broad interest in electrochemical devices,
      nonvolatile memory, neuromorphic computing, and biomimicry utilizing synthetic
      membranes. Traditional design approaches are primarily based on substitutional
      doping of dissimilar valent cations in a solid lattice, which has inherent limits
      on dopant concentration and thereby ionic conductivity. Here, we demonstrate
      perovskite nickelates as Li-ion shuttles with simultaneous suppression of
      electronic transport via Mott transition. Electrochemically lithiated SmNiO3 (Li
      SNO) contains a large amount of mobile Li+ located in interstitial sites of the
      perovskite approaching one dopant ion per unit cell. A significant lattice
      expansion associated with interstitial doping allows for fast Li+ conduction with
      reduced activation energy. We further present a generalization of this approach
      with results on other rare-earth perovskite nickelates as well as dopants such as
      Na+ The results highlight the potential of quantum materials and emergent physics
      in design of ion conductors.

PMID- 30104359
TI  - Proteomic analysis of monolayer-integrated proteins on lipid droplets identifies
      amphipathic interfacial alpha-helical membrane anchors.
AB  - Despite not spanning phospholipid bilayers, monotopic integral proteins (MIPs)
      play critical roles in organizing biochemical reactions on membrane surfaces.
      Defining the structural basis by which these proteins are anchored to membranes
      has been hampered by the paucity of unambiguously identified MIPs and a lack of
      computational tools that accurately distinguish monolayer-integrating motifs from
      bilayer-spanning transmembrane domains (TMDs). We used quantitative proteomics
      and statistical modeling to identify 87 high-confidence candidate MIPs in lipid
      droplets, including 21 proteins with predicted TMDs that cannot be accommodated
      in these monolayer-enveloped organelles. Systematic cysteine-scanning mutagenesis
      showed the predicted TMD of one candidate MIP, DHRS3, to be a partially buried
      amphipathic alpha-helix in both lipid droplet monolayers and the cytoplasmic
      leaflet of endoplasmic reticulum membrane bilayers. Coarse-grained molecular
      dynamics simulations support these observations, suggesting that this helix is
      most stable at the solvent-membrane interface. The simulations also predicted
      similar interfacial amphipathic helices when applied to seven additional MIPs
      from our dataset. Our findings suggest that interfacial helices may be a common
      motif by which MIPs are integrated into membranes, and provide high-throughput
      methods to identify and study MIPs.

PMID- 30104360
TI  - Designing antiphase boundaries by atomic control of heterointerfaces.
AB  - Extended defects are known to have critical influences in achieving desired
      material performance. However, the nature of extended defect generation is highly
      elusive due to the presence of multiple nucleation mechanisms with close
      energetics. A strategy to design extended defects in a simple and clean way is
      thus highly desirable to advance the understanding of their role, improve
      material quality, and serve as a unique playground to discover new phenomena. In
      this work, we report an approach to create planar extended defects-antiphase
      boundaries (APB) -with well-defined origins via the combination of advanced
      growth, atomic-resolved electron microscopy, first-principals calculations, and
      defect theory. In La2/3Sr1/3MnO3 thin film grown on Sr2RuO4 substrate, APBs in
      the film naturally nucleate at the step on the substrate/film interface. For a
      single step, the generated APBs tend to be nearly perpendicular to the interface
      and propragate toward the film surface. Interestingly, when two steps are close
      to each other, two corresponding APBs communicate and merge together, forming a
      unique triangle-shaped defect domain boundary. Such behavior has been ascribed,
      in general, to the minimization of the surface energy of the APB. Atomic-resolved
      electron microscopy shows that these APBs have an intriguing antipolar structure
      phase, thus having the potential as a general recipe to achieve ferroelectric
      like domain walls for high-density nonvolatile memory.

PMID- 30104361
TI  - Silkworm genetic sexing through W chromosome-linked, targeted gene integration.
AB  - Sex separation methods are critical for genetic sexing systems in commercial
      insect production and sterile insect techniques. Integration of selectable marker
      genes into a sex chromosome is particularly useful in insects with a
      heterogametic sex determination system. Here, we describe targeted gene
      integration of fluorescent marker expression cassettes into a randomly amplified
      polymorphic DNA (RAPD) marker region in the W chromosome of the lepidopteran
      model insect Bombyx mori using transcriptional activator-like effector nuclease
      (TALEN)-mediated genome editing. This silkworm strain shows ubiquitous female
      specific red or green fluorescence from the embryonic to adult stages.
      Furthermore, we developed a binary, female-specific, embryonic lethality system
      combining the TALEN and the clustered regularly interspaced short palindromic
      repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. This system
      includes one strain with TALEN-mediated, W-specific Cas9 expression driven by the
      silkworm germ cell-specific nanos (nos) promoter and another strain with U6
      derived single-guide RNA (sgRNA) expression targeting transformer 2 (tra2), an
      essential gene for silkworm embryonic development. Filial 1 (F1) hybrids exhibit
      complete female-specific lethality during embryonic stages. Our study provides a
      promising approach for B. mori genetic sexing and sheds light on developing
      sterile insect techniques in other insect species, especially in lepidopteran
      pests with WZ/ZZ sex chromosome systems.

PMID- 30104362
TI  - Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish.
AB  - During heart development and regeneration, coronary vascularization is tightly
      coupled with cardiac growth. Although inhibiting vascularization causes defects
      in the innate regenerative response of zebrafish to heart injury, angiogenic
      signals are not known to be sufficient for triggering regeneration events. Here,
      by using a transgenic reporter strain, we found that regulatory sequences of the
      angiogenic factor vegfaa are active in epicardial cells of uninjured animals, as
      well as in epicardial and endocardial tissue adjacent to regenerating muscle upon
      injury. Additionally, we find that induced cardiac overexpression of vegfaa in
      zebrafish results in overt hyperplastic thickening of the myocardial wall,
      accompanied by indicators of angiogenesis, epithelial-to-mesenchymal transition,
      and cardiomyocyte regeneration programs. Unexpectedly, vegfaa overexpression in
      the context of cardiac injury enabled ectopic cardiomyogenesis but inhibited
      regeneration at the site of the injury. Our findings identify Vegfa as one of a
      select few known factors sufficient to activate adult cardiomyogenesis, while
      also illustrating how instructive factors for heart regeneration require
      spatiotemporal control for efficacy.

PMID- 30104365
TI  - Correction for Wang et al., Molecular origin of the weak susceptibility of
      kinesin velocity to loads and its relation to the collective behavior of
      kinesins.

PMID- 30104363
TI  - Recurrent computations for visual pattern completion.
AB  - Making inferences from partial information constitutes a critical aspect of
      cognition. During visual perception, pattern completion enables recognition of
      poorly visible or occluded objects. We combined psychophysics, physiology, and
      computational models to test the hypothesis that pattern completion is
      implemented by recurrent computations and present three pieces of evidence that
      are consistent with this hypothesis. First, subjects robustly recognized objects
      even when they were rendered <15% visible, but recognition was largely impaired
      when processing was interrupted by backward masking. Second, invasive
      physiological responses along the human ventral cortex exhibited visually
      selective responses to partially visible objects that were delayed compared with
      whole objects, suggesting the need for additional computations. These
      physiological delays were correlated with the effects of backward masking. Third,
      state-of-the-art feed-forward computational architectures were not robust to
      partial visibility. However, recognition performance was recovered when the model
      was augmented with attractor-based recurrent connectivity. The recurrent model
      was able to predict which images of heavily occluded objects were easier or
      harder for humans to recognize, could capture the effect of introducing a
      backward mask on recognition behavior, and was consistent with the physiological
      delays along the human ventral visual stream. These results provide a strong
      argument of plausibility for the role of recurrent computations in making visual
      inferences from partial information.

PMID- 30104364
TI  - Tyrosyl-tRNA synthetase stimulates thrombopoietin-independent hematopoiesis
      accelerating recovery from thrombocytopenia.
AB  - New mechanisms behind blood cell formation continue to be uncovered, with
      therapeutic approaches for hematological diseases being of great interest. Here
      we report an enzyme in protein synthesis, known for cell-based activities beyond
      translation, is a factor inducing megakaryocyte-biased hematopoiesis, most likely
      under stress conditions. We show an activated form of tyrosyl-tRNA synthetase
      (YRSACT), prepared either by rationally designed mutagenesis or alternative
      splicing, induces expansion of a previously unrecognized high-ploidy Sca-1+
      megakaryocyte population capable of accelerating platelet replenishment after
      depletion. Moreover, YRSACT targets monocytic cells to induce secretion of
      transacting cytokines that enhance megakaryocyte expansion stimulating the Toll
      like receptor/MyD88 pathway. Platelet replenishment by YRSACT is independent of
      thrombopoietin (TPO), as evidenced by expansion of the megakaryocytes from
      induced pluripotent stem cell-derived hematopoietic stem cells from a patient
      deficient in TPO signaling. We suggest megakaryocyte-biased hematopoiesis induced
      by YRSACT offers new approaches for treating thrombocytopenia, boosting yields
      from cell-culture production of platelet concentrates for transfusion, and
      bridging therapy for hematopoietic stem cell transplantation.

PMID- 30104367
TI  - Evidence for the impact of the 8.2-kyBP climate event on Near Eastern early
      farmers.
AB  - The 8.2-thousand years B.P. event is evident in multiple proxy records across the
      globe, showing generally dry and cold conditions for ca. 160 years. Environmental
      changes around the event are mainly detected using geochemical or palynological
      analyses of ice cores, lacustrine, marine, and other sediments often distant from
      human settlements. The Late Neolithic excavated area of the archaeological site
      of Catalhoyuk East [Team Poznan (TP) area] was occupied for four centuries in the
      ninth and eighth millennia B.P., thus encompassing the 8.2-thousand years B.P.
      climatic event. A Bayesian analysis of 56 radiocarbon dates yielded a high
      resolution chronological model comprising six building phases, with dates ranging
      from before 8325-8205 to 7925-7815 calibrated years (cal) B.P. Here, we correlate
      an onsite paleoclimate record constructed from delta2H values of lipid biomarkers
      preserved in pottery vessels recovered from these buildings with changes in
      architectural, archaeozoological, and consumption records from well-documented
      archaeological contexts. The overall sequence shows major changes in husbandry
      and consumption practices at ca. 8.2 thousand years B.P., synchronous with
      variations in the delta2H values of the animal fat residues. Changes in
      paleoclimate and archaeological records seem connected with the patterns of
      atmospheric precipitation during the occupation of the TP area predicted by
      climate modeling. Our multiproxy approach uses records derived directly from
      documented archaeological contexts. Through this, we provide compelling evidence
      for the specific impacts of the 8.2-thousand years B.P. climatic event on the
      economic and domestic activities of pioneer Neolithic farmers, influencing
      decisions relating to settlement planning and food procurement strategies.

PMID- 30104366
TI  - The consequences of cavity creation on the folding landscape of a repeat protein
      depend upon context.
AB  - The effect of introducing internal cavities on protein native structure and
      global stability has been well documented, but the consequences of these packing
      defects on folding free-energy landscapes have received less attention. We
      investigated the effects of cavity creation on the folding landscape of the
      leucine-rich repeat protein pp32 by high-pressure (HP) and urea-dependent NMR and
      high-pressure small-angle X-ray scattering (HPSAXS). Despite a modest global
      energetic perturbation, cavity creation in the N-terminal capping motif (N-cap)
      resulted in very strong deviation from two-state unfolding behavior. In contrast,
      introduction of a cavity in the most stable, C-terminal half of pp32 led to
      highly concerted unfolding, presumably because the decrease in stability by the
      mutations attenuated the N- to C-terminal stability gradient present in WT pp32.
      Interestingly, enlarging the central cavity of the protein led to the population
      under pressure of a distinct intermediate in which the N-cap and repeats 1-4 were
      nearly completely unfolded, while the fifth repeat and the C-terminal capping
      motif remained fully folded. Thus, despite modest effects on global stability,
      introducing internal cavities can have starkly distinct repercussions on the
      conformational landscape of a protein, depending on their structural and
      energetic context.

PMID- 30104369
TI  - Testing for crowd out in social nudges: Evidence from a natural field experiment
      in the market for electricity.
AB  - This study considers the response of household electricity consumption to social
      nudges during peak load events. Our investigation considers two social nudges.
      The first targets conservation during peak load events, while the second promotes
      aggregate conservation. Using data from a natural field experiment with 42,100
      households, we find that both social nudges reduce peak load electricity
      consumption by 2 to 4% when implemented in isolation and by nearly 7% when
      implemented in combination. These findings suggest an important role for social
      nudges in the regulation of electricity markets and a limited role for crowd out
      effects.

PMID- 30104370
TI  - Profile of Michael Tomasello.

PMID- 30104368
TI  - N6-methyladenosine modification of hepatitis B virus RNA differentially regulates
      the viral life cycle.
AB  - N6-methyladenosine (m6A) RNA methylation is the most abundant epitranscriptomic
      modification of eukaryotic messenger RNAs (mRNAs). Previous reports have found
      m6A on both cellular and viral transcripts and defined its role in regulating
      numerous biological processes, including viral infection. Here, we show that m6A
      and its associated machinery regulate the life cycle of hepatitis B virus (HBV).
      HBV is a DNA virus that completes its life cycle via an RNA intermediate, termed
      pregenomic RNA (pgRNA). Silencing of enzymes that catalyze the addition of m6A to
      RNA resulted in increased HBV protein expression, but overall reduced reverse
      transcription of the pgRNA. We mapped the m6A site in the HBV RNA and found that
      a conserved m6A consensus motif situated within the epsilon stem loop structure,
      is the site for m6A modification. The epsilon stem loop is located in the 3'
      terminus of all HBV mRNAs and at both the 5' and 3' termini of the pgRNA.
      Mutational analysis of the identified m6A site in the 5' epsilon stem loop of
      pgRNA revealed that m6A at this site is required for efficient reverse
      transcription of pgRNA, while m6A methylation of the 3' epsilon stem loop results
      in destabilization of all HBV transcripts, suggesting that m6A has dual
      regulatory function for HBV RNA. Overall, this study reveals molecular insights
      into how m6A regulates HBV gene expression and reverse transcription, leading to
      an increased level of understanding of the HBV life cycle.

PMID- 30104371
TI  - How intermittent breaks in interaction improve collective intelligence.
AB  - People influence each other when they interact to solve problems. Such social
      influence introduces both benefits (higher average solution quality due to
      exploitation of existing answers through social learning) and costs (lower
      maximum solution quality due to a reduction in individual exploration for novel
      answers) relative to independent problem solving. In contrast to prior work,
      which has focused on how the presence and network structure of social influence
      affect performance, here we investigate the effects of time. We show that when
      social influence is intermittent it provides the benefits of constant social
      influence without the costs. Human subjects solved the canonical traveling
      salesperson problem in groups of three, randomized into treatments with constant
      social influence, intermittent social influence, or no social influence. Groups
      in the intermittent social-influence treatment found the optimum solution
      frequently (like groups without influence) but had a high mean performance (like
      groups with constant influence); they learned from each other, while maintaining
      a high level of exploration. Solutions improved most on rounds with social
      influence after a period of separation. We also show that storing subjects' best
      solutions so that they could be reloaded and possibly modified in subsequent
      rounds-a ubiquitous feature of personal productivity software-is similar to
      constant social influence: It increases mean performance but decreases
      exploration.

PMID- 30104372
TI  - How children come to understand false beliefs: A shared intentionality account.
AB  - To predict and explain the behavior of others, one must understand that their
      actions are determined not by reality but by their beliefs about reality.
      Classically, children come to understand beliefs, including false beliefs, at
      about 4-5 y of age, but recent studies using different response measures suggest
      that even infants (and apes!) have some skills as well. Resolving this
      discrepancy is not possible with current theories based on individual cognition.
      Instead, what is needed is an account recognizing that the key processes in
      constructing an understanding of belief are social and mental coordination with
      other persons and their (sometimes conflicting) perspectives. Engaging in such
      social and mental coordination involves species-unique skills and motivations of
      shared intentionality, especially as they are manifest in joint attention and
      linguistic communication, as well as sophisticated skills of executive function
      to coordinate the different perspectives involved. This shared intentionality
      account accords well with documented differences in the cognitive capacities of
      great apes and human children, and it explains why infants and apes pass some
      versions of false-belief tasks whereas only older children pass others.

PMID- 30104373
TI  - Evolution and function of the hominin forefoot.
AB  - The primate foot functions as a grasping organ. As such, its bones, soft tissues,
      and joints evolved to maximize power and stability in a variety of grasping
      configurations. Humans are the obvious exception to this primate pattern, with
      feet that evolved to support the unique biomechanical demands of bipedal
      locomotion. Of key functional importance to bipedalism is the morphology of the
      joints at the forefoot, known as the metatarsophalangeal joints (MTPJs), but a
      comprehensive analysis of hominin MTPJ morphology is currently lacking. Here we
      present the results of a multivariate shape and Bayesian phylogenetic comparative
      analyses of metatarsals (MTs) from a broad selection of anthropoid primates
      (including fossil apes and stem catarrhines) and most of the early hominin pedal
      fossil record, including the oldest hominin for which good pedal remains exist,
      Ardipithecus ramidus Results corroborate the importance of specific bony
      morphologies such as dorsal MT head expansion and "doming" to the evolution of
      terrestrial bipedalism in hominins. Further, our evolutionary models reveal that
      the MT1 of Ar. ramidus shifts away from the reconstructed optimum of our last
      common ancestor with apes, but not necessarily in the direction of modern humans.
      However, the lateral rays of Ar. ramidus are transformed in a more human-like
      direction, suggesting that they were the digits first recruited by hominins into
      the primary role of terrestrial propulsion. This pattern of evolutionary change
      is seen consistently throughout the evolution of the foot, highlighting the
      mosaic nature of pedal evolution and the emergence of a derived, modern hallux
      relatively late in human evolution.

PMID- 30104374
TI  - Differences in neural stem cell identity and differentiation capacity drive
      divergent regenerative outcomes in lizards and salamanders.
AB  - While lizards and salamanders both exhibit the ability to regenerate amputated
      tails, the outcomes achieved by each are markedly different. Salamanders, such as
      Ambystoma mexicanum, regenerate nearly identical copies of original tails.
      Regenerated lizard tails, however, exhibit important morphological differences
      compared with originals. Some of these differences concern dorsoventral
      patterning of regenerated skeletal and spinal cord tissues; regenerated
      salamander tail tissues exhibit dorsoventral patterning, while regrown lizard
      tissues do not. Additionally, regenerated lizard tails lack characteristically
      roof plate-associated structures, such as dorsal root ganglia. We hypothesized
      that differences in neural stem cells (NSCs) found in the ependyma of regenerated
      spinal cords account for these divergent regenerative outcomes. Through a
      combination of immunofluorescent staining, RT-PCR, hedgehog regulation, and
      transcriptome analysis, we analyzed NSC-dependent tail regeneration. Both
      salamander and lizard Sox2+ NSCs form neurospheres in culture. While salamander
      neurospheres exhibit default roof plate identity, lizard neurospheres exhibit
      default floor plate. Hedgehog signaling regulates dorsalization/ventralization of
      salamander, but not lizard, NSCs. Examination of NSC differentiation potential in
      vitro showed that salamander NSCs are capable of neural differentiation into
      multiple lineages, whereas lizard NSCs are not, which was confirmed by in vivo
      spinal cord transplantations. Finally, salamander NSCs xenogeneically
      transplanted into regenerating lizard tail spinal cords were influenced by native
      lizard NSC hedgehog signals, which favored salamander NSC floor plate
      differentiation. These findings suggest that NSCs in regenerated lizard and
      salamander spinal cords are distinct cell populations, and these differences
      contribute to the vastly different outcomes observed in tail regeneration.

PMID- 30104375
TI  - Biophysical and functional characterization of Norrin signaling through
      Frizzled4.
AB  - Wnt signaling is initiated by Wnt ligand binding to the extracellular ligand
      binding domain, called the cysteine-rich domain (CRD), of a Frizzled (Fzd)
      receptor. Norrin, an atypical Fzd ligand, specifically interacts with Fzd4 to
      activate beta-catenin-dependent canonical Wnt signaling. Much of the molecular
      basis that confers Norrin selectivity in binding to Fzd4 was revealed through the
      structural study of the Fzd4CRD-Norrin complex. However, how the ligand
      interaction, seemingly localized at the CRD, is transmitted across full-length
      Fzd4 to the cytoplasm remains largely unknown. Here, we show that a flexible
      linker domain, which connects the CRD to the transmembrane domain, plays an
      important role in Norrin signaling. The linker domain directly contributes to the
      high-affinity interaction between Fzd4 and Norrin as shown by ~10-fold higher
      binding affinity of Fzd4CRD to Norrin in the presence of the linker. Swapping the
      Fzd4 linker with the Fzd5 linker resulted in the loss of Norrin signaling,
      suggesting the importance of the linker in ligand-specific cellular response. In
      addition, structural dynamics of Fzd4 associated with Norrin binding investigated
      by hydrogen/deuterium exchange MS revealed Norrin-induced conformational changes
      on the linker domain and the intracellular loop 3 (ICL3) region of Fzd4. Cell
      based functional assays showed that linker deletion, L430A and L433A mutations at
      ICL3, and C-terminal tail truncation displayed reduced beta-catenin-dependent
      signaling activity, indicating the functional significance of these sites.
      Together, our results provide functional and biochemical dissection of Fzd4 in
      Norrin signaling.

PMID- 30104376
TI  - Structural and mechanistic analysis of the arsenate respiratory reductase
      provides insight into environmental arsenic transformations.
AB  - Arsenate respiration by bacteria was discovered over two decades ago and is
      catalyzed by diverse organisms using the well-conserved Arr enzyme complex. Until
      now, the mechanisms underpinning this metabolism have been relatively opaque.
      Here, we report the structure of an Arr complex (solved by X-ray crystallography
      to 1.6-A resolution), which was enabled by an improved Arr expression method in
      the genetically tractable arsenate respirer Shewanella sp. ANA-3. We also
      obtained structures bound with the substrate arsenate (1.8 A), the product
      arsenite (1.8 A), and the natural inhibitor phosphate (1.7 A). The structures
      reveal a conserved active-site motif that distinguishes Arr [(R/K)GRY] from the
      closely related arsenite respiratory oxidase (Arx) complex (XGRGWG). Arr activity
      assays using methyl viologen as the electron donor and arsenate as the electron
      acceptor display two-site ping-pong kinetics. A Mo(V) species was detected with
      EPR spectroscopy, which is typical for proteins with a pyranopterin guanine
      dinucleotide cofactor. Arr is an extraordinarily fast enzyme that approaches the
      diffusion limit (Km = 44.6 +/- 1.6 MUM, kcat = 9,810 +/- 220 seconds-1), and
      phosphate is a competitive inhibitor of arsenate reduction (Ki = 325 +/- 12 MUM).
      These observations, combined with knowledge of typical sedimentary arsenate and
      phosphate concentrations and known rates of arsenate desorption from minerals in
      the presence of phosphate, suggest that (i) arsenate desorption limits
      microbiologically induced arsenate reductive mobilization and (ii) phosphate
      enhances arsenic mobility by stimulating arsenate desorption rather than by
      inhibiting it at the enzymatic level.

PMID- 30104378
TI  - Maintaining trust when agents can engage in self-deception.
AB  - The coexistence of cooperation and selfish instincts is a remarkable
      characteristic of humans. Psychological research has unveiled the cognitive
      mechanisms behind self-deception. Two important findings are that a higher
      ambiguity about others' social preferences leads to a higher likelihood of acting
      selfishly and that agents acting selfishly will increase their belief that others
      are also selfish. In this work, we posit a mathematical model of these mechanisms
      and explain their impact on the undermining of a global cooperative society. We
      simulate the behavior of agents playing a prisoner's dilemma game in a random
      network of contacts. We endow each agent with these two self-deception mechanisms
      which bias her toward thinking that the other agent will defect. We study
      behavior when a fraction of agents with the "always defect" strategy is
      introduced in the network. Depending on the magnitude of the biases the players
      could start a cascade of defection or isolate the defectors. We find that there
      are thresholds above which the system approaches a state of complete distrust.

PMID- 30104377
TI  - Foxp2 regulates anatomical features that may be relevant for vocal behaviors and
      bipedal locomotion.
AB  - Fundamental human traits, such as language and bipedalism, are associated with a
      range of anatomical adaptations in craniofacial shaping and skeletal remodeling.
      However, it is unclear how such morphological features arose during hominin
      evolution. FOXP2 is a brain-expressed transcription factor implicated in a rare
      disorder involving speech apraxia and language impairments. Analysis of its
      evolutionary history suggests that this gene may have contributed to the
      emergence of proficient spoken language. In the present study, through analyses
      of skeleton-specific knockout mice, we identified roles of Foxp2 in skull shaping
      and bone remodeling. Selective ablation of Foxp2 in cartilage disrupted pup
      vocalizations in a similar way to that of global Foxp2 mutants, which may be due
      to pleiotropic effects on craniofacial morphogenesis. Our findings also indicate
      that Foxp2 helps to regulate strength and length of hind limbs and maintenance of
      joint cartilage and intervertebral discs, which are all anatomical features that
      are susceptible to adaptations for bipedal locomotion. In light of the known
      roles of Foxp2 in brain circuits that are important for motor skills and spoken
      language, we suggest that this gene may have been well placed to contribute to
      coevolution of neural and anatomical adaptations related to speech and bipedal
      locomotion.

PMID- 30104379
TI  - Deep mutational scanning of hemagglutinin helps predict evolutionary fates of
      human H3N2 influenza variants.
AB  - Human influenza virus rapidly accumulates mutations in its major surface protein
      hemagglutinin (HA). The evolutionary success of influenza virus lineages depends
      on how these mutations affect HA's functionality and antigenicity. Here we
      experimentally measure the effects on viral growth in cell culture of all single
      amino acid mutations to the HA from a recent human H3N2 influenza virus strain.
      We show that mutations that are measured to be more favorable for viral growth
      are enriched in evolutionarily successful H3N2 viral lineages relative to
      mutations that are measured to be less favorable for viral growth. Therefore,
      despite the well-known caveats about cell-culture measurements of viral fitness,
      such measurements can still be informative for understanding evolution in nature.
      We also compare our measurements for H3 HA to similar data previously generated
      for a distantly related H1 HA and find substantial differences in which amino
      acids are preferred at many sites. For instance, the H3 HA has less disparity in
      mutational tolerance between the head and stalk domains than the H1 HA. Overall,
      our work suggests that experimental measurements of mutational effects can be
      leveraged to help understand the evolutionary fates of viral lineages in nature
      but only when the measurements are made on a viral strain similar to the ones
      being studied in nature.

PMID- 30104381
TI  - Probing the non-Debye low-frequency excitations in glasses through random
      pinning.
AB  - We investigate the properties of the low-frequency spectrum in the density of
      states [Formula: see text] of a 3D model glass former. To magnify the non-Debye
      sector of the spectrum, we introduce a random pinning field that freezes a finite
      particle fraction to break the translational invariance and shifts all of the
      vibrational frequencies of the extended modes toward higher frequencies. We show
      that non-Debye soft localized modes progressively emerge as the fraction p of
      pinned particles increases. Moreover, the low-frequency tail of [Formula: see
      text] goes to zero as a power law [Formula: see text], with [Formula: see text]
      and [Formula: see text] above a threshold fraction [Formula: see text].

PMID- 30104380
TI  - RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing
      repair.
AB  - Unrestrained 53BP1 activity at DNA double-strand breaks (DSBs) hampers DNA end
      resection and upsets DSB repair pathway choice. RNF169 acts as a molecular
      rheostat to limit 53BP1 deposition at DSBs, but how this fine balance translates
      to DSB repair control remains undefined. In striking contrast to 53BP1, ChIP
      analyses of AsiSI-induced DSBs unveiled that RNF169 exhibits robust accumulation
      at DNA end-proximal regions and preferentially targets resected, RPA-bound DSBs.
      Accordingly, we found that RNF169 promotes CtIP-dependent DSB resection and
      favors homology-mediated DSB repair, and further showed that RNF169 dose
      dependently stimulates single-strand annealing repair, in part, by alleviating
      the 53BP1-imposed barrier to DSB end resection. Our results highlight the
      interplay of RNF169 with 53BP1 in fine-tuning choice of DSB repair pathways.

PMID- 30104382
TI  - Interleukin 4 is inactivated via selective disulfide-bond reduction by
      extracellular thioredoxin.
AB  - Thioredoxin 1 (TRX), an essential intracellular redox regulator, is also secreted
      by mammalian cells. Recently, we showed that TRX activates extracellular
      transglutaminase 2 via reduction of an allosteric disulfide bond. In an effort to
      identify other extracellular substrates of TRX, macrophages derived from THP-1
      cells were treated with NP161, a small-molecule inhibitor of secreted TRX. NP161
      enhanced cytokine outputs of alternatively activated macrophages, suggesting that
      extracellular TRX regulated the activity of interleukin 4 (IL-4) and/or
      interleukin 13 (IL-13). To test this hypothesis, the C35S mutant of human TRX was
      shown to form a mixed disulfide bond with recombinant IL-4 but not IL-13. Kinetic
      analysis revealed a kcat/KM value of 8.1 MUM-1?min-1 for TRX-mediated recognition
      of IL-4, which established this cytokine as the most selective partner of
      extracellular TRX to date. Mass spectrometry identified the C46-C99 bond of IL-4
      as the target of TRX, consistent with the essential role of this disulfide bond
      in IL-4 activity. To demonstrate the physiological relevance of our biochemical
      findings, recombinant TRX was shown to attenuate IL-4-dependent proliferation of
      cultured TF-1 erythroleukemia cells and also to inhibit the progression of
      chronic pancreatitis in an IL-4-driven mouse model of this disease. By
      establishing that IL-4 is posttranslationally regulated by TRX-promoted reduction
      of a disulfide bond, our findings highlight a novel regulatory mechanism of the
      type 2 immune response that is specific to IL-4 over IL-13.

PMID- 30104384
TI  - Human exonization through differential nucleosome occupancy.
AB  - Nucleosomal modifications have been implicated in fundamental epigenetic
      regulation, but the roles of nucleosome occupancy in shaping changes through
      evolution remain to be addressed. Here we present high-resolution nucleosome
      occupancy profiles for multiple tissues derived from human, macaque, tree shrew,
      mouse, and pig. Genome-wide comparison reveals conserved nucleosome occupancy
      profiles across both different species and tissue types. Notably, we found
      significantly higher levels of nucleosome occupancy in exons than in introns, a
      pattern correlated with the different exon-intron GC content. We then determined
      whether this biased occupancy may play roles in the origination of new exons
      through evolution, rather than being a downstream effect of exonization, through
      a comparative approach to sequentially trace the order of the exonization and
      biased nucleosome binding. By identifying recently evolved exons in human but not
      in macaque using matched RNA sequencing, we found that higher exonic nucleosome
      occupancy also existed in macaque regions orthologous to these exons. Presumably,
      such biased nucleosome occupancy facilitates the origination of new exons by
      increasing the splice strength of the ancestral nonexonic regions through driving
      a local difference in GC content. These data thus support a model that sites
      bound by nucleosomes are more likely to evolve into exons, which we term the
      "nucleosome-first" model.

PMID- 30104383
TI  - Seed genome hypomethylated regions are enriched in transcription factor genes.
AB  - The precise mechanisms that control gene activity during seed development remain
      largely unknown. Previously, we showed that several genes essential for seed
      development, including those encoding storage proteins, fatty acid biosynthesis
      enzymes, and transcriptional regulators (e.g., ABI3, FUS3) are located within
      hypomethylated regions of the soybean genome. These hypomethylated regions are
      similar to the DNA methylation valleys (DMVs), or canyons, found in mammalian
      cells. Here, we address the question of the extent to which DMVs are present
      within seed genomes and what role they might play in seed development. We scanned
      soybean and Arabidopsis seed genomes from postfertilization through dormancy and
      germination for regions that contain <5% or <0.4% bulk methylation in CG, CHG,
      and CHH contexts over all developmental stages. We found that DMVs represent
      extensive portions of seed genomes, range in size from 5-76 kb, are scattered
      throughout all chromosomes, and are hypomethylated throughout the plant life
      cycle. Significantly, DMVs are enriched greatly in transcription factor (TF)
      genes and other developmental genes that play critical roles in seed formation.
      Many DMV genes are regulated with respect to seed stage, region, and tissue, and
      contain H3K4me3, H3K27me3, or bivalent marks that fluctuate during development.
      Our results indicate that DMVs are a unique regulatory feature of both plant and
      animal genomes, and that a large number of seed genes are regulated in the
      absence of methylation changes during development, probably by the action of
      specific TFs and epigenetic events at the chromatin level.

PMID- 30104385
TI  - Regulation of axon repulsion by MAX-1 SUMOylation and AP-3.
AB  - During neural development, growing axons express specific surface receptors in
      response to various environmental guidance cues. These axon guidance receptors
      are regulated through intracellular trafficking and degradation to enable
      navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5
      receptor is necessary for dorsal migration of developing motor axons. We
      previously found that MAX-1 is required for UNC-5-mediated axon repulsion, but
      its mechanism of action remained unclear. Here, we demonstrate that UNC-5
      mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation
      and the AP-3 complex beta subunit gene, apb-3 Genetic interaction studies show
      that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3 Biochemical
      analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is
      weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive
      interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5
      receptor into the lysosome for protein degradation. In vivo fluorescence recovery
      after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are
      required for proper trafficking of UNC-5 receptor in the axon. Our results
      demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3
      mediated trafficking and degradation of UNC-5 receptors during axon guidance.

PMID- 30104386
TI  - JUM is a computational method for comprehensive annotation-free analysis of
      alternative pre-mRNA splicing patterns.
AB  - Alternative pre-mRNA splicing (AS) greatly diversifies metazoan transcriptomes
      and proteomes and is crucial for gene regulation. Current computational analysis
      methods of AS from Illumina RNA-sequencing data rely on preannotated libraries of
      known spliced transcripts, which hinders AS analysis with poorly annotated
      genomes and can further mask unknown AS patterns. To address this critical
      bioinformatics problem, we developed a method called the junction usage model
      (JUM) that uses a bottom-up approach to identify, analyze, and quantitate global
      AS profiles without any prior transcriptome annotations. JUM accurately reports
      global AS changes in terms of the five conventional AS patterns and an additional
      "composite" category composed of inseparable combinations of conventional
      patterns. JUM stringently classifies the difficult and disease-relevant pattern
      of intron retention (IR), reducing the false positive rate of IR detection
      commonly seen in other annotation-based methods to near-negligible rates. When
      analyzing AS in RNA samples derived from Drosophila heads, human tumors, and
      human cell lines bearing cancer-associated splicing factor mutations, JUM
      consistently identified approximately twice the number of novel AS events missed
      by other methods. Computational simulations showed JUM exhibits a 1.2 to 4.8
      times higher true positive rate at a fixed cutoff of 5% false discovery rate. In
      summary, JUM provides a framework and improved method that removes the necessity
      for transcriptome annotations and enables the detection, analysis, and
      quantification of AS patterns in complex metazoan transcriptomes with superior
      accuracy.

PMID- 30104388
TI  - Electron tomography reveals details of the internal microstructure of
      desalination membranes.
AB  - As water availability becomes a growing challenge in various regions throughout
      the world, desalination and wastewater reclamation through technologies such as
      reverse osmosis (RO) are becoming more important. Nevertheless, many open
      questions remain regarding the internal structure of thin-film composite RO
      membranes. In this work, fully aromatic polyamide films that serve as the active
      layer of state-of-the-art water filtration membranes were investigated using high
      angle annular dark-field scanning transmission electron microscopy tomography.
      Reconstructions of the 3D morphology reveal intricate aspects of the complex
      microstructure not visible from 2D projections. We find that internal voids of
      the active layer of compressed commercial membranes account for less than 0.2% of
      the total polymer volume, contrary to previously reported values that are two
      orders of magnitude higher. Measurements of the local variation in polyamide
      density from electron tomography reveal that the polymer density is highest at
      the permeable surface for the two membranes tested and establish the significance
      of surface area on RO membrane transport properties. The same type of analyses
      could provide explanations for different flux variations with surface area for
      other types of membranes where the density is distributed differently. Thus, 3D
      reconstructions and quantitative analyses will be crucial to characterize the
      complex morphology of polymeric membranes used in next-generation water
      purification membranes.

PMID- 30104387
TI  - Deciphering the super relaxed state of human beta-cardiac myosin and the mode of
      action of mavacamten from myosin molecules to muscle fibers.
AB  - Mutations in beta-cardiac myosin, the predominant motor protein for human heart
      contraction, can alter power output and cause cardiomyopathy. However,
      measurements of the intrinsic force, velocity, and ATPase activity of myosin have
      not provided a consistent mechanism to link mutations to muscle pathology. An
      alternative model posits that mutations in myosin affect the stability of a
      sequestered, super relaxed state (SRX) of the protein with very slow ATP
      hydrolysis and thereby change the number of myosin heads accessible to actin.
      Here we show that purified human beta-cardiac myosin exists partly in an SRX and
      may in part correspond to a folded-back conformation of myosin heads observed in
      muscle fibers around the thick filament backbone. Mutations that cause
      hypertrophic cardiomyopathy destabilize this state, while the small molecule
      mavacamten promotes it. These findings provide a biochemical and structural link
      between the genetics and physiology of cardiomyopathy with implications for
      therapeutic strategies.

PMID- 30104391
TI  - Adversity and resilience: 10 lessons I have learnt from working with children in
      humanitarian emergencies.

PMID- 30104390
TI  - Maternal mental health and childhood injury: evidence from the UK Millennium
      Cohort Study.
AB  - OBJECTIVE: We assessed whether maternal mental health problems increased rates
      for child injury during the preschool years and mid-childhood, and the extent to
      which associations could be accounted for by a range of potential explanatory
      factors. DESIGN: We analysed the UK Millennium Cohort Study, a nationally
      representative sample with data collected throughout childhood. Multinomial
      regression was used to investigate whether two measures of maternal mental health
      (diagnosed depression/anxiety and psychological distress) were associated with
      subsequent childhood injury. Models adjusted for sociodemographics, parenting and
      child externalising behaviours. MAIN OUTCOME MEASURE: Maternal report of
      unintentional injuries (none, 1, 2+) recorded at three data collection periods (3
      5 years; 5-7 years; 7-11 years). RESULTS: The analytic sample comprised n=9240
      families who participated 3-11 years with complete data on exposures and outcomes
      (multiply imputing missing covariates). Exposure to maternal mental health
      problems was associated with increased rates of subsequent childhood injuries.
      Associations attenuated after adjustment for potential explanatory factors,
      although they remained elevated. For example, high maternal distress was
      associated with injuries 3-5 years (adjusted relative risk ratio (aRRR): 1
      injury=1.18, 95% CI 0.86 to 1.61; 2+ injuries=2.22, 95% CI 1.22 to 4.02);
      injuries 5-7 years (aRRR: 1 injury=1.31, 95% CI 0.97 to 1.76; 2+ injuries=1.84,
      95% CI 1.09 to 3.09); and injuries 7-11 years (aRRR: 1 injury=1.03, 95% CI 0.81
      to 1.31; 2+ injuries=1.33, 95% CI 0.97 to 1.81). CONCLUSIONS: Children exposed to
      mothers with mental health problems had higher rates of childhood injury than
      those not exposed. If further investigation of this association suggests
      causality then it will be important to test measures that address mothers' mental
      health issues with a view to reducing injuries among their children.

PMID- 30104392
TI  - Falls in paediatric Charcot-Marie-Tooth disease: a 6-month prospective cohort
      study.
AB  - OBJECTIVE: To prospectively study falls in children and adolescents with Charcot
      Marie-Tooth disease (CMT). DESIGN: Prospective cohort study. SETTING:
      Neuromuscular outpatient clinic of a tertiary paediatric hospital. PATIENTS:
      Sixty children and adolescents ('children') aged 4-18 years, 30 with CMT and 30
      typically developing (TD). MAIN OUTCOME MEASURES: Falls rate over 6 months and
      falls characteristics questionnaire. RESULTS: Twenty-two children with CMT
      reported falling at least once in 6 months compared with eight TD children (CMT
      2819 (0-1915), TD 31 (0-6) total falls (range)). Detailed falls characteristics
      were collected from 242 individual falls (CMT 216, TD 26). Injurious falls were
      reported by 19 children with CMT (74 falls) compared with 2 TD children (3
      falls), with cuts, grazes and bruising most common. No fractures were sustained
      and no child required hospitalisation. However, 12 injuries from falls in
      children with CMT required management by a healthcare provider, versus none in TD
      children. Tripping was the most common mechanism of falls in both groups. Age was
      the strongest predictor of falls (rho=-0.53, p=0.006) with all children (CMT and
      TD) aged <7 years falling. Balance was the strongest impairment-related predictor
      of falls (rho=-0.47, p=0.02). The conservative estimate of risk of falls in
      children and adolescents with CMT was 33 times higher than their TD peers
      (incidence rate ratio=32.8, 95% CI 10.2 to 106.0). CONCLUSIONS: Children and
      adolescents with CMT fall more often than TD peers and sustain more injuries when
      they fall.

PMID- 30104389
TI  - Endoribonuclease ENDU-2 regulates multiple traits including cold tolerance via
      cell autonomous and nonautonomous controls in Caenorhabditis elegans.
AB  - Environmental temperature acclimation is essential to animal survival, yet
      thermoregulation mechanisms remain poorly understood. We demonstrate cold
      tolerance in Caenorhabditis elegans as regulated by paired ADL chemosensory
      neurons via Ca2+-dependent endoribonuclease (EndoU) ENDU-2. Loss of ENDU-2
      function results in life span, brood size, and synaptic remodeling abnormalities
      in addition to enhanced cold tolerance. Enzymatic ENDU-2 defects localized in the
      ADL and certain muscle cells led to increased cold tolerance in endu-2 mutants.
      Ca2+ imaging revealed ADL neurons were responsive to temperature stimuli through
      transient receptor potential (TRP) channels, concluding that ADL function
      requires ENDU-2 action in both cell-autonomous and cell-nonautonomous mechanisms.
      ENDU-2 is involved in caspase expression, which is central to cold tolerance and
      synaptic remodeling in dorsal nerve cord. We therefore conclude that ENDU-2
      regulates cell type-dependent, cell-autonomous, and cell-nonautonomous cold
      tolerance.

PMID- 30104393
TI  - Question 1: Is there a role for the ketogenic diet in refractory status
      epilepticus?

PMID- 30104395
TI  - Heartbeat: The ongoing controversy of intervention for chronic total coronary
      occlusions.

PMID- 30104394
TI  - Kawasaki disease: a prospective population survey in the UK and Ireland from 2013
      to 2015.
AB  - OBJECTIVE: Kawasaki disease (KD) is an increasingly common vasculitis with risk
      of coronary artery aneurysms (CAAs). The last UK survey was in 1990, whereas
      current epidemiology, treatment patterns and complication rates are unknown. The
      aim of this study was to address this knowledge gap. METHODS: A British
      Paediatric Surveillance Unit survey in the UK and Ireland from 1 January 2013 to
      28 February 2015 ascertained demographics, ethnicity, seasonal incidence,
      treatment and complication rates. RESULTS: 553 cases were notified: 389 had
      complete KD, 46 had atypical KD and 116 had incomplete KD; 2 were diagnosed at
      postmortem with an incidence of 4.55/100 000 children under 5 years, with a male
      to female ratio of 1.5:1 and a median age of 2.7 years (2.5 months-15 years).
      Presentation was highest in January and in rural areas. Most were white (64%),
      and Chinese and Japanese Asians were over-represented as were black African or
      African mixed-race children. 94% received intravenous immunoglobulin (IVIG). The
      overall CAA rate was 19%, and all-cardiac complications affected 28%. Those with
      CAA received IVIG later than in those without (median 10 days vs 7 days). Those
      under 1 year had fewer symptoms, but the highest CAA rate (39%). Overall 8 of 512
      cases (1.6%) had giant CAA, and 4 of 86 cases (5%) under 1 year of age developed
      giant CAA. Mortality from KD was 0.36%. CONCLUSIONS: The UK and Ireland incidence
      of KD has increased and is more frequently seen in winter and rural areas.
      Delayed IVIG treatment is associated with CAA, suggesting earlier and adjunctive
      primary treatment might reduce complications to prevent CAA, particularly in the
      very young.

PMID- 30104396
TI  - Partial atrioventricular septal defect in infancy: don't we need to know more?

PMID- 30104397
TI  - Soluble PD-1 ligands regulate T-cell function in Waldenstrom macroglobulinemia.
AB  - Although immune checkpoint molecules regulate the progression of certain cancers,
      their significance in malignant development of Waldenstrom macroglobulinemia
      (WM), an incurable low-grade B-cell lymphoma, remains unknown. Recently,
      cytokines in the bone marrow (BM) microenvironment are shown to contribute to the
      pathobiology of WM. Here, we investigated the impact of cytokines, including
      interleukin-6 (IL-6) and IL-21, on immune regulation and particularly on the
      programmed death-1 (PD-1) and its ligands PD-L1 and PD-L2. We showed that IL-21,
      interferon gamma, and IL-6 significantly induced PD-L1 and PD-L2 gene expression
      in WM cell lines. Increased PD-L1 and PD-L2 messenger RNA was also detected in
      patients' BM cells. Patients' nonmalignant BM cells, including T cells and
      monocytes, showed increased PD-L1, but minimal or undetectable PD-L2 surface
      expression. There was also very modest PD-L1 and PD-L2 surface expression by
      malignant WM cells, suggesting that ligands are cleaved from the cell surface.
      Levels of soluble ligands were higher in patients' BM plasma and blood serum than
      controls. Furthermore, IL-21 and IL-6 increased secreted PD-L1 in the culture
      media of WM cell lines, implying that elevated levels of soluble PD-1 ligands are
      cytokine mediated. Soluble PD-1 ligands reduced T-cell proliferation,
      phosphorylated extracellular signal-regulated kinase and cyclin A levels,
      mitochondrial adenosine triphosphate production, and spare respiratory capacity.
      In conclusion, we identify that soluble PD-1 ligands are elevated in WM patients
      and, in addition to surface-bound ligands in WM BM, could regulate T-cell
      function. Given the capability of secreted forms to be bioactive at distant
      sites, soluble PD-1 ligands have the potential to promote disease progression in
      WM.

PMID- 30104398
TI  - Altered brain metabolites in patients with diabetes mellitus and related
      complications - evidence from 1H MRS study.
AB  - In recent years, diabetes mellitus (DM) has been acknowledged as an important
      factor for brain disorders. Significant alterations in brain metabolism have been
      demonstrated during the development of DM and its complications. Magnetic
      resonance spectroscopy (MRS), a cutting-edge technique used in biochemical
      analyses, non-invasively provides insights into altered brain metabolite levels
      in vivo This review aims to discuss current MRS data describing brain metabolite
      levels in DM patients with or without complications. Cerebral metabolites
      including N-acetylaspartate (NAA), creatine (Cr), choline (Cho), myo-inositol
      (mI), glutamate, and glutamine were significantly altered in DM patients,
      suggesting that energy metabolism, neurotransmission, and lipid membrane
      metabolism might be disturbed during the progression of DM. Changes in brain
      metabolites may be non-invasive biomarkers for DM and DM-related complications.
      Different brain regions presented distinct metabolic signatures, indicating
      region-specific diabetic brain damages. In addition to serving as biomarkers, MRS
      data on brain metabolites can also shed light on diabetic treatment monitoring.
      For example, exercise may restore altered brain metabolite levels and has
      beneficial effects on cognition in DM patients. Future studies should validate
      the above findings in larger populations and uncover the mechanisms of DM-induced
      brain damages.

PMID- 30104399
TI  - Sorting machineries: how platelet-dense granules differ from alpha-granules.
AB  - Platelets respond to vascular injury via surface receptor stimulation and
      signaling events to trigger aggregation, procoagulant activation, and granule
      secretion during hemostasis, thrombosis, and vascular remodeling. Platelets
      contain three major types of secretory granules including dense granules (or
      delta-granules, DGs), alpha-granules (AGs), and lysosomes. The contents of
      platelet granules are specific. Platelet DGs store polyphosphate and small
      molecules such as ADP, ATP, Ca2+, and serotonin, while AGs package most of the
      proteins that platelets release. The platelet DGs and AGs are regarded as being
      budded from the endosomes and the trans-Golgi network (TGN), respectively, and
      then matured from multivesicular bodies (MVBs). However, the sorting machineries
      between DGs and AGs are different. Inherited platelet disorders are associated
      with deficiency of DGs and AGs, leading to bleeding diathesis in patients with
      Hermansky-Pudlak syndrome (HPS), gray platelet syndrome (GPS), and
      arthrogryposis, renal dysfunction, and cholestasis syndrome (ARC). Here, we
      reviewed the current understanding about how DGs differ from AGs in structure,
      biogenesis, and function. In particular, we focus on the sorting machineries that
      are involved in the formation of these two types of granules to provide insights
      into their diverse biological functions.

PMID- 30104400
TI  - The N-terminal polypeptide derived from vMIP-II exerts its anti-tumor activity in
      human breast cancer by regulating lncRNA SPRY4-IT1.
AB  - Accumulating evidence demonstrates that long non-coding RNA (lncRNA) sprouty4
      intron transcript 1 (lncRNA SPRY4-IT1) plays a vital role in the development of
      breast cancer. However, the underlying mechanism has not been eventually
      illuminated. We aimed to explore the biological activity of lncRNA SPRY4-IT1 in
      breast cancer cells and whether N-terminal polypeptide derived from viral
      macrophage inflammatory protein II (NT21MP) could exert its anti-tumor effect by
      regulating lncRNA SPRY4-IT1 and its target gene SKA2 Real-time RT-PCR, Western
      blotting, wound healing, and invasion assays were used to achieve this goal. We
      found that lncRNA SPRY4-IT1 was highly expressed in breast cancer cells.
      Moreover, NT21MP markedly inhibited biological effects of breast cancer cells by
      regulating lncRNA SPRY4-IT1, which was partially achieved through SKA2. Our
      findings suggested that lncRNA SPRY4-IT1 could serve as a novel biomarker by
      NT21MP for breast cancer.

PMID- 30104401
TI  - A pan-cancer study of the transcriptional regulation of uricogenesis in human
      tumours: pathological and pharmacological correlates.
AB  - Uric acid (UA) is the end product of the catabolism of purines, and its serum
      levels are commonly increased in cancer patients. We aimed to explore the
      transcriptional regulation of tumour uricogenesis in human tumours, and relate
      uricogenesis with tumour pathological and pharmacological findings. Using data
      from The Cancer Genome Atlas (TCGA), we analysed the expression levels of
      xanthine dehydrogenase (XDH) and adenine phosphoribosyltransferase (APRT), two
      key enzymes in UA production and the purine salvage pathway, respectively. We
      found large differences between tumour types and individual tumours in their
      expression of XDH and APRT Variations in locus-specific DNA methylation and gene
      copy number correlated with the expression levels of XDH and APRT in human
      tumours respectively. We explored the consequences of this differential
      regulation of uricogenesis. Tumours with high levels of XDH mRNA were
      characterised by higher expression of several genes encoding pro-inflammatory and
      immune cytokines, and increased levels of tumour infiltration with immune cells.
      Finally, we studied cancer drug sensitivity using data from the National Cancer
      Institute-60 (NCI-60) database. A specific correlation was found between the
      expression levels of APRT and cell sensitivity to the chemotherapeutic agent 5
      fluorouracil (5-FU). Our findings underline the existence of great differences in
      uricogenesis between different types of human tumours. The study of uricogenesis
      offers promising perspectives for the identification of clinically relevant
      molecular biomarkers and for tumour stratification in the therapeutic context.

PMID- 30104403
TI  - CORRECTION.

PMID- 30104402
TI  - The prognostic values of the peroxiredoxins family in ovarian cancer.
AB  - Purpose: Peroxiredoxins (PRDXs) are a family of antioxidant enzymes with six
      identified mammalian isoforms (PRDX1-6). PRDX expression is up-regulated in
      various types of solid tumors; however, individual PRDX expression, and its
      impact on prognostic value in ovarian cancer patients, remains unclear.Methods:
      PRDXs family protein expression profiles in normal ovarian tissues and ovarian
      cancer tissues were examined using the Human Protein Atlas database. Then, the
      prognostic roles of PRDX family members in several sets of clinical data
      (histology, pathological grades, clinical stages, and applied chemotherapy) in
      ovarian cancer patients were investigated using the Kaplan-Meier plotter.Results:
      PRDXs family protein expression in ovarian cancer tissues was elevated compared
      with normal ovarian tissues. Meanwhile, elevated expression of PRDX3, PRDX5, and
      PRDX6 mRNAs showed poorer overall survival (OS); PRDX5 and PRDX6 also predicted
      poor progression-free survival (PFS) for ovarian cancer patients. Furthermore,
      PRDX3 played significant prognostic roles, particularly in poor differentiation
      and late-stage serous ovarian cancer patients. Additionally, PRDX5 predicted a
      lower PFS in all ovarian cancer patients treated with Platin, Taxol, and
      Taxol+Platin chemotherapy. PRDX3 and PRDX6 also showed poor PFS in patients
      treated with Platin chemotherapy. Furthermore, PRDX3 and PRDX5 indicated lower OS
      in patients treated with these three chemotherapeutic agents. PRDX6 predicted a
      poorer OS in patients treated with Taxol and Taxol+Platin
      chemotherapy.Conclusion: These results suggest that there are distinct prognostic
      values of PRDX family members in patients with ovarian cancer, and that the
      expression of PRDX3, PRDX5, and PRDX6 mRNAs are a useful prognostic indicator in
      the effect of chemotherapy in ovarian cancer patients.

PMID- 30104404
TI  - Evaluating the Functional Pore Size of Chloroplast TOC and TIC Protein
      Translocons: Import of Folded Proteins.
AB  - The degree of residual structure retained by proteins while passing through
      biological membranes is a fundamental mechanistic question of protein
      translocation. Proteins are generally thought to be unfolded while transported
      through canonical proteinaceous translocons, including the translocons of the
      outer and inner chloroplast envelope membranes (TOC and TIC). Here, we
      readdressed the issue and found that the TOC/TIC translocons accommodated the
      tightly folded dihydrofolate reductase (DHFR) protein in complex with its
      stabilizing ligand, methotrexate (MTX). We employed a fluorescein-conjugated
      methotrexate (FMTX), which has slow membrane transport rates relative to
      unconjugated MTX, to show that the rate of ligand accumulation inside
      chloroplasts is faster when bound to DHFR that is actively being imported.
      Stromal accumulation of FMTX is ATP dependent when DHFR is actively being
      imported but is otherwise ATP independent, again indicating DHFR/FMTX complex
      import. Furthermore, the TOC/TIC pore size was probed with fixed-diameter
      particles and found to be greater than 25.6 A, large enough to support folded
      DHFR import and also larger than mitochondrial and bacterial protein translocons
      that have a requirement for protein unfolding. This unique pore size and the
      ability to import folded proteins have critical implications regarding the
      structure and mechanism of the TOC/TIC translocons.

PMID- 30104405
TI  - Integrated Regulation of Apical Hook Development by Transcriptional Coupling of
      EIN3/EIL1 and PIFs in Arabidopsis.
AB  - The apical hook protects the meristems of dicot seedlings as they protrude
      through the soil; multiple factors, including phytohormones and light, mediate
      apical hook development. HOOKLESS1 (HLS1) plays an indispensable role, as HLS1
      mutations cause a hookless phenotype. The ETHYLENE INSENSITIVE3 (EIN3) and EIN3
      LIKE1 (EIL1) transcription factors integrate multiple signals (ethylene,
      gibberellins, and jasmonate) and activate HLS1 expression to enhance hook
      development. Here, we found that Arabidopsis thaliana PHYTOCHROME INTERACTING
      FACTOR (PIF) transcription factors act in parallel with EIN3/EIL1 and promote
      hook curvature by activating HLS1 transcription at a distinct binding motif.
      EIN3/EIL1 and PIFs can promote hook formation in the absence of the other.
      Jasmonate represses PIF function to inhibit hook development. Like EIN3 and EIL1,
      MYC2 interacts with PIF4 and hampers its activity. Acting together, EIN3/EIL1 and
      PIFs alleviate the negative effects of jasmonate/light and facilitate the
      positive effects of ethylene/gibberellins. Mutating EIN3/EIL1 and PIFs causes a
      complete hookless phenotype, marginal HLS1 expression, and insensitivity to
      upstream signals. Transcriptome profiling revealed that EIN3/EIL1 and PIFs
      additively and distinctly regulate a wide array of processes, including apical
      hook development. Together, our findings identify an integrated framework
      underlying the regulation of apical hook development and show that EIN3/EIL1 and
      PIFs fine-tune adaptive growth in response to hormone and light signals.

PMID- 30104408
TI  - Testing messages about comparative risk of electronic cigarettes and combusted
      cigarettes.
AB  - INTRODUCTION: Health agencies are grappling with communicating risks of
      electronic cigarettes (e-cigarettes) compared with combusted cigarettes. This
      study examined smokers' responses to two types of comparative risk messages with
      one type incorporating more negative antismoking elements in the design. METHODS:
      In an online experiment, 1400 US adult (18+ years) current smokers and recent
      quitters were randomised to view one of three comparative risk messages about e
      cigarettes (CR messages), one of three comparative risk messages that included
      more negative antismoking elements in the design (CR- messages) or a control
      message. Selection of outcomes was guided by the antismoking message impact
      framework. Multivariate analyses of covariance and logistic regression models
      analysed effects of messages on message evaluations, e-cigarette-related and
      cigarette-related beliefs and behavioural intentions. RESULTS: Both CR and CR-
      messages decreased smokers' intentions to smoke cigarettes, increased intentions
      to switch to e-cigarettes completely and increased perceptions that e-cigarettes
      are less harmful than combusted cigarettes. Neither message type increased dual
      use intentions relative to exclusive e-cigarettes use or smoking cessation. CR
      messages decreased perceived absolute risks of e-cigarettes and self-exempting
      beliefs about smoking, whereas CR- versus CR messages produced higher self
      efficacy to quit smoking. CONCLUSION: Comparative risk communication might
      encourage smokers to switch to lower-harm tobacco products. Comparative risk
      messages with more negative antismoking elements in the design might be
      particularly effective, because they led to higher self-efficacy to quit smoking.
      Regulatory agencies may consider using comparative risk messages with more
      negative antismoking elements to educate the public about lower risk of e
      cigarettes.

PMID- 30104409
TI  - Content analysis of tobacco content in UK television.
AB  - AIMS: Exposure to audiovisual tobacco content in media is a risk factor for
      smoking in young people. While tobacco content in films has been extensively
      documented, content in mainstream television has received relatively little
      attention. We report an analysis of tobacco content in a sample of UK free-to-air
      prime-time television broadcasts in 2015, and compare this with a similar
      analysis from 2010. DESIGN: Content analysis of all programmes and advertisements
      or trailers broadcast on the five national UK free-to-air channels in the UK
      between 18:00 and 22:00 during three separate weeks in September, October and
      November 2015. SETTING: Great Britain. PARTICIPANTS: None (media analysis only).
      MEASUREMENTS: Occurrence of any tobacco, tobacco use, implied use, other tobacco
      reference/related objects and branding in every 1 min coding interval. FINDINGS:
      Tobacco content occurred in 33% of all programmes and 8% of all adverts or
      programme trailer breaks. Actual tobacco use occurred in 12% of all programmes
      broadcast. Tobacco-related objects, primarily no smoking signs, occurred in 2% of
      broadcasts; implied tobacco use and tobacco branding were also rare. The majority
      of tobacco content occurred after the 21:00 watershed. CONCLUSIONS: These
      findings are virtually unchanged from our earlier analysis of programme content
      from 2010. Audiovisual tobacco content remains common in UK television
      programmes.

PMID- 30104407
TI  - Histone H2A-H2B binding by Pol alpha in the eukaryotic replisome contributes to
      the maintenance of repressive chromatin.
AB  - The eukaryotic replisome disassembles parental chromatin at DNA replication
      forks, but then plays a poorly understood role in the re-deposition of the
      displaced histone complexes onto nascent DNA. Here, we show that yeast DNA
      polymerase alpha contains a histone-binding motif that is conserved in human Pol
      alpha and is specific for histones H2A and H2B. Mutation of this motif in budding
      yeast cells does not affect DNA synthesis, but instead abrogates gene silencing
      at telomeres and mating-type loci. Similar phenotypes are produced not only by
      mutations that displace Pol alpha from the replisome, but also by mutation of the
      previously identified histone-binding motif in the CMG helicase subunit Mcm2, the
      human orthologue of which was shown to bind to histones H3 and H4. We show that
      chromatin-derived histone complexes can be bound simultaneously by Mcm2, Pol
      alpha and the histone chaperone FACT that is also a replisome component. These
      findings indicate that replisome assembly unites multiple histone-binding
      activities, which jointly process parental histones to help preserve silent
      chromatin during the process of chromosome duplication.

PMID- 30104410
TI  - Mass Spectrometry-Based Absolute Quantification of Single Xenopus Embryo
      Proteomes.
AB  - Early Xenopus development is characterized by a poor correlation between global
      mRNA and protein abundances due to maternal mRNA and protein loading. Therefore,
      proteome profiling is necessary to study gene expression dynamics during early
      Xenopus development. In contrast to mammals, single Xenopus eggs and embryos
      contain enough protein to allow identification and quantification of thousands of
      proteins using mass spectrometry-based proteomics. In addition to investigating
      developmental processes, single egg or blastomere proteomes can be used to study
      cell-to-cell variability at an unprecedented depth. In this protocol, we describe
      a mass spectrometry-based proteomics approach for the identification and absolute
      quantification of Xenopus laevis egg or embryo proteomes, including sample
      preparation, peptide fractionation and separation, and data analysis.

PMID- 30104411
TI  - Lymphocyte Deficiency Induced by Sublethal Irradiation in Xenopus.
AB  - In many studies of diseases affecting amphibians, it is important to determine to
      what extent lymphocyte-mediated defenses are involved. For example, in studies of
      the nature of the immune response of Xenopus laevis to the amphibian chytrid
      fungus, Batrachochytrium dendrobatidis, it was essential to determine if mucosal
      antimicrobial peptides or lymphocyte-mediated immunity was most important for
      resistance to this skin pathogen. In this protocol, we describe a method for
      sublethal irradiation to reduce lymphocyte numbers. Briefly, X. laevis adults or
      tadpoles are exposed to 9 Gy (900 rads) of irradiation applied by exposure to a
      cesium source or gamma irradiator to reduce lymphocyte populations in the spleen.

PMID- 30104406
TI  - The PEAT protein complexes are required for histone deacetylation and
      heterochromatin silencing.
AB  - In eukaryotes, heterochromatin regions are typically subjected to transcriptional
      silencing. DNA methylation has an important role in such silencing and has been
      studied extensively. However, little is known about how methylated
      heterochromatin regions are subjected to silencing. We conducted a genetic screen
      and identified an epcr (enhancer of polycomb-related) mutant that releases
      heterochromatin silencing in Arabidopsis thaliana We demonstrated that EPCR1
      functions redundantly with its paralog EPCR2 and interacts with PWWP domain
      containing proteins (PWWPs), AT-rich interaction domain-containing proteins
      (ARIDs), and telomere repeat binding proteins (TRBs), thus forming multiple
      functionally redundant protein complexes named PEAT (PWWPs-EPCRs-ARIDs-TRBs). The
      PEAT complexes mediate histone deacetylation and heterochromatin condensation and
      thereby facilitate heterochromatin silencing. In heterochromatin regions, the
      production of small interfering RNAs (siRNAs) and DNA methylation is repressed by
      the PEAT complexes. The study reveals how histone deacetylation, heterochromatin
      condensation, siRNA production, and DNA methylation interplay with each other and
      thereby maintain heterochromatin silencing.

PMID- 30104412
TI  - Bond swapping from a charge cloud allows flexible coordination of upstream
      signals through WASP: Multiple regulatory roles for the WASP basic region.
AB  - Wiskott-Aldrich syndrome protein (WASP) activates the actin-related protein 2/3
      homolog (Arp2/3) complex and regulates actin polymerization in a physiological
      setting. Cell division cycle 42 (Cdc42) is a key activator of WASP, which binds
      Cdc42 through a Cdc42/Rac-interactive binding (CRIB)-containing region that
      defines a subset of Cdc42 effectors. Here, using site-directed mutagenesis and
      binding affinity determination and kinetic assays, we report the results of an
      investigation into the energetic contributions of individual WASP residues to
      both the Cdc42-WASP binding interface and the kinetics of complex formation. Our
      results support the previously proposed dock-and-coalesce binding mechanism,
      initiated by electrostatic steering driven by WASP's basic region and followed by
      a coalescence phase likely driven by the conserved CRIB motif. The WASP basic
      region, however, appears also to play a role in the final complex, as its
      mutation affected both on- and off-rates, suggesting a more comprehensive
      physiological role for this region centered on the C-terminal triad of positive
      residues. These results highlight the expanding roles of the basic region in WASP
      and other CRIB-containing effector proteins in regulating complex cellular
      processes and coordinating multiple input signals. The data presented improve our
      understanding of the Cdc42-WASP interface and also add to the body of information
      available for Cdc42-effector complex formation, therapeutic targeting of which
      has promise for Ras-driven cancers. Our findings suggest that combining high
      affinity peptide-binding sequences with short electrostatic steering sequences
      could increase the efficacy of peptidomimetic candidates designed to interfere
      with Cdc42 signaling in cancer.

PMID- 30104413
TI  - Structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase-dihydropteroate
      synthase from Plasmodium vivax sheds light on drug resistance.
AB  - The genomes of the malaria-causing Plasmodium parasites encode a protein fused of
      6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and dihydropteroate
      synthase (DHPS) domains that catalyze sequential reactions in the folate
      biosynthetic pathway. Whereas higher organisms derive folate from their diet and
      lack the enzymes for its synthesis, most eubacteria and a number of lower
      eukaryotes including malaria parasites synthesize tetrahydrofolate via DHPS.
      Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) HPPK-DHPSs are currently
      targets of drugs like sulfadoxine (SDX). The SDX effectiveness as an antimalarial
      drug is increasingly diminished by the rise and spread of drug-resistant
      mutations. Here, we present the crystal structure of PvHPPK-DHPS in complex with
      four substrates/analogs, revealing the bifunctional PvHPPK-DHPS architecture in
      an unprecedented state of enzymatic activation. SDX's effect on HPPK-DHPS is due
      to 4-amino benzoic acid (pABA) mimicry, and the PvHPPK-DHPS structure sheds light
      on the SDX-binding cavity, as well as on mutations that effect SDX potency. We
      mapped five dominant drug resistance mutations in PvHPPK-DHPS: S382A, A383G,
      K512E/D, A553G, and V585A, most of which occur individually or in clusters
      proximal to the pABA-binding site. We found that these resistance mutations
      subtly alter the intricate enzyme/pABA/SDX interactions such that DHPS affinity
      for pABA is diminished only moderately, but its affinity for SDX is changed
      substantially. In conclusion, the PvHPPK-DHPS structure rationalizes and unravels
      the structural bases for SDX resistance mutations and highlights architectural
      features in HPPK-DHPSs from malaria parasites that can form the basis for
      developing next-generation anti-folate agents to combat malaria parasites.

PMID- 30104415
TI  - Germline and Somatic NF1 Alterations Are Linked to Increased HER2 Expression in
      Breast Cancer.
AB  - NF1 germline mutation predisposes to breast cancer. NF1 mutations have also been
      proposed as oncogenic drivers in sporadic breast cancers. To understand the
      genomic and histologic characteristics of these breast cancers, we analyzed the
      tumors with NF1 germline mutations and also examined the genomic and proteomic
      profiles of unselected tumors. Among 14 breast cancer specimens from 13 women
      affected with neurofibromatosis type 1 (NF1), 9 samples (NF + BrCa) underwent
      genomic copy number (CN) and targeted sequencing analysis. Mutations of NF1 were
      identified in two samples and TP53 were in three. No mutation was detected in
      ATM, BARD1, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD50, and STK11
      HER2 (ErbB2) overexpression was detected by IHC in 69.2% (9/13) of the tumors. CN
      gain/amplification of ERBB2 was detected in 4 of 9 with DNA analysis. By
      evaluating HER2 expression and NF1 alterations in unselected invasive breast
      cancers in TCGA datasets, we discovered that among samples with ERBB2 CN
      gain/amplification, the HER2 mRNA and protein expression were much more
      pronounced in NF1-mutated/deleted samples in comparison with NF1-unaltered
      samples. This finding suggests a synergistic interplay between these two genes,
      potentially driving the development of breast cancer harboring NF1 mutation and
      ERBB2 CN gain/amplification. NF1 gene loss of heterozygosity was observed in 4 of
      9 NF + BrCa samples. CDK4 appeared to have more CN gain in NF + BrCa and
      exhibited increased mRNA expression in TCGA NF1--altered samples. Cancer Prev
      Res; 11(10); 655-64. (c)2018 AACR.

PMID- 30104416
TI  - Routine use of chest x-ray for low-risk patients undergoing a periodic health
      examination: a retrospective cohort study.
AB  - BACKGROUND: Many evidence-based recommendations advocate against the use of
      routine chest x-rays for asymptomatic, low-risk outpatients; however, it is
      unclear how regularly chest x-rays are ordered in primary care. Our study aims to
      describe the frequency of, and variation in, routine chest x-ray use in low-risk
      outpatients among primary care physicians. METHODS: In this retrospective cohort
      study, Ontario residents aged 18 years and older with a periodic health
      examination (PHE) between Apr. 1, 2010, and Mar. 31, 2015, were identified via
      administrative claims data. Patients with a recent history (last 3 years) of any
      of the following were excluded: cardiac or pulmonary disease, high-risk
      comorbidity (e.g., diabetes), consultations/visits or procedures involving
      cardiac or pulmonary specialists, cancer and severe chest trauma. The primary
      outcome, a routine chest x-ray, was defined as at least 1 chest x-ray claim
      within 7 days after a PHE. RESULTS: While a routine chest x-ray followed only
      2.42% of 2 847 508 PHEs, one-quarter of family physicians (499/2031) ordered
      chest x-rays for more than 5.0% of their PHEs (interquartile range 1.5%-5.0%) and
      accounted for 62.9% of all tests observed. Routine chest x-ray use declined by
      2.0% per quarter (adjusted rate ratio 0.98, 95% confidence interval [CI] 0.97
      0.98). Older age (45-64 yr v. 18-44 yr, adjusted odds ratio [OR] 1.82, 95% CI
      1.78-1.86; >= 65 yr v. 18-44 yr, adjusted OR 2.48, 95% CI 2.39-2.58) and male sex
      of the patient (OR 2.19, 95% CI 2.14-2.24) and male sex of the provider (OR 1.55,
      95% CI 1.51-1.59) were significantly associated with increased odds of a routine
      chest x-ray being ordered. INTERPRETATION: It is relatively uncommon for a chest
      x-ray to be ordered as part of a PHE in Ontario; however, the substantial
      variation observed among physicians suggests potential for interventions targeted
      at the most frequent users.

PMID- 30104414
TI  - TNF-alpha elicits phenotypic and functional alterations of vascular smooth muscle
      cells by miR-155-5p-dependent down-regulation of cGMP-dependent kinase 1.
AB  - cGMP-dependent protein kinase 1 (PKG1) plays an important role in nitric oxide
      (NO)/cGMP-mediated maintenance of vascular smooth muscle cell (VSMC) phenotype
      and vasorelaxation. Inflammatory cytokines, including tumor necrosis factor-alpha
      (TNFalpha), have long been understood to mediate several inflammatory vascular
      diseases. However, the underlying mechanism of TNFalpha-dependent inflammatory
      vascular disease is unclear. Here, we found that TNFalpha treatment decreased
      PKG1 expression in cultured VSMCs, which correlated with NF-kappaB-dependent
      biogenesis of miR-155-5p that targeted the 3'-UTR of PKG1 mRNA. TNFalpha induced
      VSMC phenotypic switching from a contractile to a synthetic state through the
      down-regulation of VSMC marker genes, suppression of actin polymerization,
      alteration of cell morphology, and elevation of cell proliferation and migration.
      All of these events were blocked by treatment with an inhibitor of miR-155-5p or
      PKG1, whereas transfection with miR-155-5p mimic or PKG1 siRNA promoted
      phenotypic modulation, similar to the response to TNFalpha. In addition, TNFalpha
      induced miR-155-5p inhibited the vasorelaxant response of de-endothelialized
      mouse aortic vessels to 8-Br-cGMP by suppressing phosphorylation of myosin
      phosphatase and myosin light chain, both of which are downstream signal
      modulators of PKG1. Moreover, TNFalpha-induced VSMC phenotypic alteration and
      vasodilatory dysfunction were blocked by NF-kappaB inhibition. These results
      suggest that TNFalpha impairs NO/cGMP-mediated maintenance of the VSMC
      contractile phenotype and vascular relaxation by down-regulating PKG1 through NF
      kappaB-dependent biogenesis of miR-155-5p. Thus, the NF-kappaB/miR-155-5p/PKG1
      axis may be crucial in the pathogenesis of inflammatory vascular diseases, such
      as atherosclerotic intimal hyperplasia and preeclamptic hypertension.

PMID- 30104417
TI  - Validation of 5 key colonoscopy-related data elements from Ontario health
      administrative databases compared to the clinical record: a cross-sectional
      study.
AB  - BACKGROUND: Colonoscopy is used widely, but its quality is highly variable, which
      may adversely affect patients. Research and quality-improvement initiatives in a
      variety of jurisdictions have sought to address this issue, often supported by
      the use of health administrative data. As these data are generally not collected
      for these purposes, it is critical to measure their validity before use. The aim
      of this study was to validate health administrative data definitions for 5 key
      colonoscopy elements through comparison to the clinical record. METHODS: In a
      cross-sectional study, we randomly sampled 1968 colonoscopy and noncolonoscopy
      procedures performed at 23 hospitals and 5 nonhospital endoscopy clinics between
      April 2008 and March 2009 in Ontario. We compared definitions for 5 key
      colonoscopy elements (colonoscopy case, colonoscopy setting, colonoscopy
      completeness, anesthesiologist assistance and polypectomy) derived from the
      health administrative data to the clinical record. We calculated weighted and
      unweighted sensitivity, specificity and positive predictive value, adjusted for
      clustering of patients within physicians, for each definition relative to the
      reference standard. RESULTS: We abstracted 1845 records; in 1282 cases (69.5%),
      colonoscopy was intended or performed. The weighted sensitivity and specificity
      of colonoscopy case, nonhospital colonoscopy setting and anesthesiologist
      assistance exceeded 95%. The weighted sensitivity for colonoscopy completeness
      and polypectomy exceeded 95%, but specificity was less than 90%. INTERPRETATION:
      Ontario health administrative data definitions for 5 key colonoscopy data
      elements performed well, with sensitivity and specificity values acceptable for
      use in research and quality-improvement initiatives. In jurisdictions where
      health administrative data are similarly used for research or quality
      improvement, similar studies could be considered.

PMID- 30104419
TI  - Unraveling mitotic protein networks by 3D multiplexed epitope drug screening.
AB  - Three-dimensional protein localization intricately determines the functional
      coordination of cellular processes. The complex spatial context of protein
      landscape has been assessed by multiplexed immunofluorescent staining or mass
      spectrometry, applied to 2D cell culture with limited physiological relevance or
      tissue sections. Here, we present 3D SPECS, an automated technology for 3D
      Spatial characterization of Protein Expression Changes by microscopic Screening.
      This workflow comprises iterative antibody staining, high-content 3D imaging, and
      machine learning for detection of mitoses. This is followed by mapping of spatial
      protein localization into a spherical, cellular coordinate system, a basis for
      model-based prediction of spatially resolved affinities of proteins. As a proof
      of-concept, we mapped twelve epitopes in 3D-cultured spheroids and investigated
      the network effects of twelve mitotic cancer drugs. Our approach reveals novel
      insights into spindle fragility and chromatin stress, and predicts unknown
      interactions between proteins in specific mitotic pathways. 3D SPECS's ability to
      map potential drug targets by multiplexed immunofluorescence in 3D cell culture
      combined with our automated high-content assay will inspire future functional
      protein expression and drug assays.

PMID- 30104418
TI  - Data-independent acquisition-based SWATH-MS for quantitative proteomics: a
      tutorial.
AB  - Many research questions in fields such as personalized medicine, drug screens or
      systems biology depend on obtaining consistent and quantitatively accurate
      proteomics data from many samples. SWATH-MS is a specific variant of data
      independent acquisition (DIA) methods and is emerging as a technology that
      combines deep proteome coverage capabilities with quantitative consistency and
      accuracy. In a SWATH-MS measurement, all ionized peptides of a given sample that
      fall within a specified mass range are fragmented in a systematic and unbiased
      fashion using rather large precursor isolation windows. To analyse SWATH-MS data,
      a strategy based on peptide-centric scoring has been established, which typically
      requires prior knowledge about the chromatographic and mass spectrometric
      behaviour of peptides of interest in the form of spectral libraries and peptide
      query parameters. This tutorial provides guidelines on how to set up and plan a
      SWATH-MS experiment, how to perform the mass spectrometric measurement and how to
      analyse SWATH-MS data using peptide-centric scoring. Furthermore, concepts on how
      to improve SWATH-MS data acquisition, potential trade-offs of parameter settings
      and alternative data analysis strategies are discussed.

PMID- 30104423
TI  - Confronting the Nonmedical Costs of Childhood Hospitalizations.

PMID- 30104421
TI  - Lost Earnings and Nonmedical Expenses of Pediatric Hospitalizations.
AB  - BACKGROUND AND OBJECTIVES: Hospitalization-related nonmedical costs, including
      lost earnings and expenses such as transportation, meals, and child care, can
      lead to challenges in prioritizing postdischarge decisions. In this study, we
      quantify such costs and evaluate their relationship with sociodemographic
      factors, including family-reported financial and social hardships. METHODS: This
      was a cross-sectional analysis of data collected during the Hospital-to-Home
      Outcomes Study, a randomized trial designed to determine the effects of a nurse
      home visit after standard pediatric discharge. Parents completed an in-person
      survey during the child's hospitalization. The survey included sociodemographic
      characteristics of the parent and child, measures of financial and social
      hardship, household income and also evaluated the family's total nonmedical cost
      burden, which was defined as all lost earnings plus expenses. A daily cost burden
      (DCB) standardized it for a 24-hour period. The daily cost burden as a percentage
      of daily household income (DCBi) was also calculated. RESULTS: Median total cost
      burden for the 1372 households was $113, the median DCB was $51, and the median
      DCBi was 45%. DCB and DCBi varied across many sociodemographic characteristics.
      In particular, single-parent households (those with less work flexibility and
      more financial hardships experienced significantly higher DCB and DCBi. Those who
      reported >=3 financial hardships lost or spent 6-times more of their daily income
      on nonmedical costs than those without hardships. Those with >=1 social hardships
      lost or spent double their daily income compared with those without social
      hardships. CONCLUSIONS: Nonmedical costs place burdens on families of children
      who are hospitalized, disproportionately affecting those with competing
      socioeconomic challenges.

PMID- 30104422
TI  - Legislation to Increase Uptake of HPV Vaccination and Adolescent Sexual
      Behaviors.
AB  - BACKGROUND: Despite preventive health benefits of the human papillomavirus (HPV)
      vaccination, uptake in the United States remains low. Twenty-four states have
      enacted legislation regarding HPV vaccination and education. One reason these
      policies have been controversial is because of concerns that they encourage risky
      adolescent sexual behaviors. Our aim in this study is to determine if state HPV
      legislation is associated with changes in adolescent sexual behaviors. METHODS:
      This is a difference-in-difference study in which we use data on adolescent
      sexual behaviors from the school-based state Youth Risk Behavior Surveillance
      System from 2001 to 2015. Sexual behaviors included ever having sexual
      intercourse in the last 3 months and condom use during last sexual intercourse.
      We compared changes in sexual behaviors among high school students before and
      after HPV legislation to changes among high school students in states without
      legislation. RESULTS: A total of 715 338 participants reported ever having sexual
      intercourse in the last 3 months, and 217 077 sexually active participants
      reported recent condom use. We found no substantive or statistically significant
      associations between HPV legislation and adolescent sexual behaviors. Recent
      sexual intercourse decreased by 0.90 percentage points (P = .21), and recent
      condom use increased by 0.96 percentage points (P = .32) among adolescents in
      states that enacted legislation compared with states that did not. Results were
      robust to a number of sensitivity analyses. CONCLUSIONS: Implementation of HPV
      legislation was not associated with changes in adolescent sexual behaviors in the
      United States. Concern that legislation will increase risky adolescent sexual
      behaviors should not be used when deciding to pass HPV legislation.

PMID- 30104420
TI  - Detecting Rare Mutations with Heterogeneous Effects Using a Family-Based Genetic
      Random Field Method.
AB  - The genetic etiology of many complex diseases is highly heterogeneous. A complex
      disease can be caused by multiple mutations within the same gene or mutations in
      multiple genes at various genomic loci. Although these disease-susceptibility
      mutations can be collectively common in the population, they are often
      individually rare or even private to certain families. Family-based studies are
      powerful for detecting rare variants enriched in families, which is an important
      feature for sequencing studies due to the heterogeneous nature of rare variants.
      In addition, family designs can provide robust protection against population
      stratification. Nevertheless, statistical methods for analyzing family-based
      sequencing data are underdeveloped, especially those accounting for heterogeneous
      etiology of complex diseases. In this article, we introduce a random field
      framework for detecting gene-phenotype associations in family-based sequencing
      studies, referred to as family-based genetic random field (FGRF). Similar to
      existing family-based association tests, FGRF could utilize within-family and
      between-family information separately or jointly to test an association. We
      demonstrate that FGRF has comparable statistical power with existing methods when
      there is no genetic heterogeneity, but can improve statistical power when there
      is genetic heterogeneity across families. The proposed method also shares the
      same advantages with the conventional family-based association tests (e.g., being
      robust to population stratification). Finally, we applied the proposed method to
      a sequencing data from the Minnesota Twin Family Study, and revealed several
      genes, including SAMD14, potentially associated with alcohol dependence.

PMID- 30104424
TI  - Prenatal Tetanus, Diphtheria, Acellular Pertussis Vaccination and Autism Spectrum
      Disorder.
AB  - : : media-1vid110.1542/5803567555001PEDS-VA_2018-0120Video Abstract BACKGROUND:
      Increasing vaccination of pregnant women makes it important to assess safety
      events potentially linked to prenatal vaccination. This study investigates the
      association between prenatal tetanus, diphtheria, acellular pertussis (Tdap)
      vaccination and autism spectrum disorder (ASD) risk in offspring. METHODS: This
      is a retrospective cohort study of mother-child pairs with deliveries January 1,
      2011 to December 31, 2014 at Kaiser Permanente Southern California hospitals.
      Maternal Tdap vaccination from pregnancy start to delivery date was obtained from
      electronic medical records. A diagnosis of ASD was obtained by using
      International Classification of Diseases, Ninth and Tenth Revision codes.
      Children were managed from birth to first ASD diagnosis, end of membership, or
      end of follow-up (June 30, 2017). Cox proportional hazards models estimated the
      unadjusted and adjusted hazard ratios (HRs) for the association between maternal
      Tdap vaccination and ASD, with inverse probability of treatment weighting to
      adjust for confounding. RESULTS: Women vaccinated were more likely to be Asian
      American or Pacific Islander, be nulliparous, have a higher education, receive
      influenza vaccination prenatally, and give birth at term. ASD was diagnosed in
      1341 (1.6%) children, and the incidence rate was 3.78 per 1000 person years in
      the Tdap exposed and 4.05 per 1000 person years in the unexposed group (HR: 0.98,
      95% confidence interval: 0.88-1.09). The inverse probability of treatment
      weighting-adjusted analyses revealed that prenatal Tdap vaccination was not
      associated with an increased ASD risk (HR: 0.85, 95% confidence interval: 0.77
      0.95). CONCLUSIONS: Prenatal Tdap vaccination was not associated with an
      increased ASD risk. We support recommendations to vaccinate pregnant women to
      protect infants, who are at highest risk of death after pertussis infection.

PMID- 30104425
TI  - Measuring and understanding individual differences in cognition.
AB  - Individuals vary in their cognitive performance. While this variation forms the
      foundation of the study of human psychometrics, its broader importance is only
      recently being recognized. Explicitly acknowledging this individual variation
      found in both humans and non-human animals provides a novel opportunity to
      understand the mechanisms, development and evolution of cognition. The papers in
      this special issue highlight the growing emphasis on individual cognitive
      differences from fields as diverse as neurobiology, experimental psychology and
      evolutionary biology. Here, we synthesize this body of work. We consider the
      distinct challenges in quantifying individual differences in cognition and
      provide concrete methodological recommendations. In particular, future studies
      would benefit from using multiple task variants to ensure they target specific,
      clearly defined cognitive traits and from conducting repeated testing to assess
      individual consistency. We then consider how neural, genetic, developmental and
      behavioural factors may generate individual differences in cognition. Finally, we
      discuss the potential fitness consequences of individual cognitive variation and
      place these into an evolutionary framework with testable hypotheses. We intend
      for this special issue to stimulate researchers to position individual variation
      at the centre of the cognitive sciences.This article is part of the theme issue
      'Causes and consequences of individual differences in cognitive abilities'.

PMID- 30104427
TI  - Linking personality and cognition: a meta-analysis.
AB  - In the past decade, several conceptual papers have linked variation in animal
      personality to variation in cognition, and recent years have seen a flood of
      empirical studies testing this link. However, these results have not been
      synthesized in a quantitative way. Here, we systematically search the literature
      and conduct a phylogenetically controlled meta-analysis of empirical papers that
      have tested the relationship between animal personality (exploration, boldness,
      activity, aggression and sociability) and cognition (initial learning/reversal
      speed, number of correct choices/errors after standard training). We find
      evidence for a small but significant relationship between variation in
      personality and variation in learning across species in the absolute scale;
      however, the direction of this relationship is highly variable and when both
      positive and negative effect sizes are considered, the average effect size does
      not differ significantly from zero. Importantly, this variation among studies is
      not explained by differences in personality or learning measure, or taxonomic
      grouping. Further, these results do not support current hypotheses suggesting
      that that fast-explorers are fast-learners or that slow-explorers perform better
      on tests of reversal learning. Rather, we find evidence that bold animals are
      faster learners, but only when boldness is measured in response to a predator (or
      simulated predator) and not when boldness is measured by exposure to a novel
      object (or novel food). Further, although only a small sub-sample of papers
      reported results separately for males and females, sex explained a significant
      amount of variation in effect size. These results, therefore, suggest that, while
      personality and learning are indeed related across a range of species, the
      direction of this relationship is highly variable. Thus further empirical work is
      needed to determine whether there are important moderators of this
      relationship.This article is part of the theme issue 'Causes and consequences of
      individual differences in cognitive abilities'.

PMID- 30104428
TI  - Comparative psychometrics: establishing what differs is central to understanding
      what evolves.
AB  - Cognitive abilities cannot be measured directly. What we can measure is
      individual variation in task performance. In this paper, we first make the case
      for why we should be interested in mapping individual differences in task
      performance onto particular cognitive abilities: we suggest that it is crucial
      for examining the causes and consequences of variation both within and between
      species. As a case study, we examine whether multiple measures of inhibitory
      control for non-human animals do indeed produce correlated task performance;
      however, no clear pattern emerges that would support the notion of a common
      cognitive ability underpinning individual differences in performance. We advocate
      a psychometric approach involving a three-step programme to make theoretical and
      empirical progress: first, we need tasks that reveal signature limits in
      performance. Second, we need to assess the reliability of individual differences
      in task performance. Third, multi-trait multi-method test batteries will be
      instrumental in validating cognitive abilities. Together, these steps will help
      us to establish what varies between individuals that could impact their fitness
      and ultimately shape the course of the evolution of animal minds. Finally, we
      propose executive functions, including working memory, inhibitory control and
      attentional shifting, as a sensible starting point for this endeavour.This
      article is part of the theme issue 'Causes and consequences of individual
      differences in cognitive abilities'.

PMID- 30104426
TI  - The repeatability of cognitive performance: a meta-analysis.
AB  - Behavioural and cognitive processes play important roles in mediating an
      individual's interactions with its environment. Yet, while there is a vast
      literature on repeatable individual differences in behaviour, relatively little
      is known about the repeatability of cognitive performance. To further our
      understanding of the evolution of cognition, we gathered 44 studies on individual
      performance of 25 species across six animal classes and used meta-analysis to
      assess whether cognitive performance is repeatable. We compared repeatability (R)
      in performance (1) on the same task presented at different times (temporal
      repeatability), and (2) on different tasks that measured the same putative
      cognitive ability (contextual repeatability). We also addressed whether R
      estimates were influenced by seven extrinsic factors (moderators): type of
      cognitive performance measurement, type of cognitive task, delay between tests,
      origin of the subjects, experimental context, taxonomic class and publication
      status. We found support for both temporal and contextual repeatability of
      cognitive performance, with mean R estimates ranging between 0.15 and 0.28.
      Repeatability estimates were mostly influenced by the type of cognitive
      performance measures and publication status. Our findings highlight the
      widespread occurrence of consistent inter-individual variation in cognition
      across a range of taxa which, like behaviour, may be associated with fitness
      outcomes.This article is part of the theme issue 'Causes and consequences of
      individual differences in cognitive abilities'.

PMID- 30104429
TI  - A distributed brain network predicts general intelligence from resting-state
      human neuroimaging data.
AB  - Individual people differ in their ability to reason, solve problems, think
      abstractly, plan and learn. A reliable measure of this general ability, also
      known as intelligence, can be derived from scores across a diverse set of
      cognitive tasks. There is great interest in understanding the neural
      underpinnings of individual differences in intelligence, because it is the single
      best predictor of long-term life success. The most replicated neural correlate of
      human intelligence to date is total brain volume; however, this coarse
      morphometric correlate says little about function. Here, we ask whether
      measurements of the activity of the resting brain (resting-state fMRI) might also
      carry information about intelligence. We used the final release of the Young
      Adult Human Connectome Project (N = 884 subjects after exclusions), providing a
      full hour of resting-state fMRI per subject; controlled for gender, age and brain
      volume; and derived a reliable estimate of general intelligence from scores on
      multiple cognitive tasks. Using a cross-validated predictive framework, we
      predicted 20% of the variance in general intelligence in the sampled population
      from their resting-state connectivity matrices. Interestingly, no single
      anatomical structure or network was responsible or necessary for this prediction,
      which instead relied on redundant information distributed across the brain.This
      article is part of the theme issue 'Causes and consequences of individual
      differences in cognitive abilities'.

PMID- 30104430
TI  - Heritabilities and co-variation among cognitive traits in red junglefowl.
AB  - Natural selection can act on between-individual variation in cognitive abilities,
      yet evolutionary responses depend on the presence of underlying genetic
      variation. It is, therefore, crucial to determine the relative extent of genetic
      versus environmental control of these among-individual differences in cognitive
      traits to understand their causes and evolutionary potential. We investigated
      heritability of associative learning performance and of a cognitive judgement
      bias (optimism), as well as their covariation, in a captive pedigree-bred
      population of red junglefowl (Gallus gallus, n > 300 chicks over 5 years). We
      analysed performance in discriminative and reversal learning (two facets of
      associative learning), and cognitive judgement bias, by conducting animal models
      to disentangle genetic from environmental contributions. We demonstrate moderate
      heritability for reversal learning, and weak to no heritability for optimism and
      discriminative learning, respectively. The two facets of associative learning
      were weakly negatively correlated, consistent with hypothesized trade-offs
      underpinning individual cognitive styles. Reversal, but not discriminative
      learning performance, was associated with judgement bias; less optimistic
      individuals reversed a previously learnt association faster. Together these
      results indicate that genetic and environmental contributions differ among
      traits. While modular models of cognitive abilities predict a lack of common
      genetic control for different cognitive traits, further investigation is required
      to fully ascertain the degree of covariation between a broader range of cognitive
      traits and the extent of any shared genetic control.This article is part of the
      theme issue 'Causes and consequences of individual differences in cognitive
      abilities'.

PMID- 30104432
TI  - Environmentally induced changes to brain morphology predict cognitive
      performance.
AB  - The relationship between the size and structure of a species' brain and its
      cognitive capacity has long interested scientists. Generally, this work relates
      interspecific variation in brain anatomy with performance on a variety of
      cognitive tasks. However, brains are known to show considerable short-term
      plasticity in response to a range of social, ecological and environmental
      factors. Despite this, we have a remarkably poor understanding of how this
      impacts on an animal's cognitive performance. Here, we non-invasively manipulated
      the relative size of brain regions associated with processing visual and chemical
      information in fish (the optic tectum and olfactory bulbs, respectively). We then
      tested performance in a cognitive task in which information from the two sensory
      modalities was in conflict. Although the fish could effectively use both visual
      and chemical information if presented in isolation, when they received cues from
      both modalities simultaneously, those with a relatively better developed optic
      tectum showed a greater reliance on visual information, while individuals with
      relatively better developed olfactory bulbs showed a greater reliance on chemical
      information. These results suggest that short-term changes in brain structure,
      possibly resulting from an attempt to minimize the costs of developing
      unnecessary but energetically expensive brain regions, may have marked effects on
      cognitive performance.This article is part of the theme issue 'Causes and
      consequences of individual differences in cognitive abilities'.

PMID- 30104431
TI  - The gut microbiome as a driver of individual variation in cognition and
      functional behaviour.
AB  - Research into proximate and ultimate mechanisms of individual cognitive variation
      in animal populations is a rapidly growing field that incorporates physiological,
      behavioural and evolutionary investigations. Recent studies in humans and
      laboratory animals have shown that the enteric microbial community plays a
      central role in brain function and development. The 'gut-brain axis' represents a
      multi-directional signalling system that encompasses neurological, immunological
      and hormonal pathways. In particular it is tightly linked with the hypothalamic
      pituitary-adrenal axis (HPA), a system that regulates stress hormone release and
      influences brain development and function. Experimental examination of the
      microbiome through manipulation of diet, infection, stress and exercise, suggests
      direct effects on cognition, including learning and memory. However, our
      understanding of these processes in natural populations is extremely limited.
      Here, we outline how recent advances in predominantly laboratory-based microbiome
      research can be applied to understanding individual differences in cognition.
      Experimental manipulation of the microbiome across natal and adult environments
      will help to unravel the interplay between cognitive variation and the gut
      microbial community. Focus on individual variation in the gut microbiome and
      cognition in natural populations will reveal new insight into the environmental
      and evolutionary constraints that drive individual cognitive variation.This
      article is part of the theme issue 'Causes and consequences of individual
      differences in cognitive abilities'.

PMID- 30104434
TI  - The impact of environmental interventions among mouse siblings on the
      heritability and malleability of general cognitive ability.
AB  - General cognitive ability can be highly heritable in some species, but at the
      same time, is very malleable. This apparent paradox could potentially be
      explained by gene-environment interactions and correlations that remain hidden
      due to experimental limitations on human research and blind spots in animal
      research. Here, we shed light on this issue by combining the design of a sibling
      study with an environmental intervention administered to laboratory mice. The
      analysis included 58 litters of four full-sibling genetically heterogeneous CD-1
      male mice, for a total of 232 mice. We separated the mice into two subsets of
      siblings: a control group (maintained in standard laboratory conditions) and an
      environmental-enrichment group (which had access to continuous physical exercise
      and daily exposure to novel environments). We found that general cognitive
      ability in mice has substantial heritability (24% for all mice) and is also
      malleable. The mice that experienced the enriched environment had a mean
      intelligence score that was 0.44 standard deviations higher than their siblings
      in the control group (equivalent to gains of 6.6 IQ points in humans). We also
      found that the estimate of heritability changed between groups (55% in the
      control group compared with non-significant 15% in the enrichment group),
      analogous to findings in humans across socio-economic status. Unexpectedly, no
      evidence of gene-environment interaction was detected, and so the change in
      heritability might be best explained by higher environmental variance in the
      enrichment group. Our findings, as well as the 'sibling intervention procedure'
      for mice, may be valuable to future research on the heritability, mechanisms and
      evolution of cognition.This article is part of the theme issue 'Causes and
      consequences of individual differences in cognitive abilities'.

PMID- 30104433
TI  - An intraspecific appraisal of the social intelligence hypothesis.
AB  - The prevailing hypotheses for the evolution of cognition focus on either the
      demands associated with group living (the social intelligence hypothesis (SIH))
      or ecological challenges such as finding food. Comparative studies testing these
      hypotheses have generated highly conflicting results; consequently, our
      understanding of the drivers of cognitive evolution remains limited. To
      understand how selection shapes cognition, research must incorporate an
      intraspecific approach, focusing on the causes and consequences of individual
      variation in cognition. Here, we review the findings of recent intraspecific
      cognitive research to investigate the predictions of the SIH. Extensive evidence
      from our own research on Australian magpies (Cracticus tibicen dorsalis), and a
      number of other taxa, suggests that individuals in larger social groups exhibit
      elevated cognitive performance and, in some cases, elevated reproductive fitness.
      Not only do these findings demonstrate how the social environment has the
      potential to shape cognitive evolution, but crucially, they demonstrate the
      importance of considering both genetic and developmental factors when attempting
      to explain the causes of cognitive variation.This article is part of the theme
      issue 'Causes and consequences of individual differences in cognitive abilities'.

PMID- 30104435
TI  - Stress hormones, social associations and song learning in zebra finches.
AB  - The use of information provided by others is a common short-cut adopted to inform
      decision-making. However, instead of indiscriminately copying others, animals are
      often selective in what, when and whom they copy. How do they decide which
      'social learning strategy' to use? Previous research indicates that stress
      hormone exposure in early life may be important: while juvenile zebra finches
      copied their parents' behaviour when solving novel foraging tasks, those exposed
      to elevated levels of corticosterone (CORT) during development copied only
      unrelated adults. Here, we tested whether this switch in social learning strategy
      generalizes to vocal learning. In zebra finches, juvenile males often copy their
      father's song; would CORT-treated juveniles in free-flying aviaries switch to
      copying songs of other males? We found that CORT-treated juveniles copied their
      father's song less accurately as compared to control juveniles. We hypothesized
      that this could be due to having weaker social foraging associations with their
      fathers, and found that sons that spent less time foraging with their fathers
      produced less similar songs. Our findings are in line with a novel hypothesis
      linking early-life stress and social learning: early-life CORT exposure may
      affect social learning indirectly as a result of the way it shapes social
      affiliations.This article is part of the theme issue 'Causes and consequences of
      individual differences in cognitive abilities'.

PMID- 30104436
TI  - Habitat and social context affect memory phenotype, exploration and covariance
      among these traits.
AB  - Individual differences in cognitive ability are predicted to covary with other
      behavioural traits such as exploration and boldness. Selection within different
      habitats may act to either enhance or break down covariance among traits;
      alternatively, changing the environmental context in which traits are assessed
      may result in plasticity that alters trait covariance. Pond snails, Lymnaea
      stagnalis, from two laboratory strains (more than 20 generations in captivity)
      and F1 laboratory reared from six wild populations were tested for long-term
      memory and exploration traits (speed and thigmotaxis) following maintenance in
      grouped and isolated conditions to determine if isolation: (i) alters memory and
      exploration; and (ii) alters covariance between memory and exploration.
      Populations that demonstrated strong memory formation (longer duration) under
      grouped conditions demonstrated weaker memory formation and reduced both speed
      and thigmotaxis following isolation. In wild populations, snails showed no
      relationship between memory and exploration in grouped conditions; however,
      following isolation, exploration behaviour was negatively correlated with memory,
      i.e. slow-explorers showing low levels of thigmotaxis formed stronger memories.
      Laboratory strains demonstrated no covariance among exploration traits and memory
      independent of context. Together these data demonstrate that the relationship
      between cognition and exploration traits can depend on both habitat and context
      specific trait plasticity.This article is part of the theme issue 'Causes and
      consequences of individual differences in cognitive abilities'.

PMID- 30104437
TI  - How does cognition shape social relationships?
AB  - The requirements of living in social groups, and forming and maintaining social
      relationships are hypothesized to be one of the major drivers behind the
      evolution of cognitive abilities. Most empirical studies investigating the
      relationships between sociality and cognition compare cognitive performance
      between species living in systems that differ in social complexity. In this
      review, we ask whether and how individuals benefit from cognitive skills in their
      social interactions. Cognitive abilities, such as perception, attention,
      learning, memory, and inhibitory control, aid in forming and maintaining social
      relationships. We investigate whether there is evidence that individual variation
      in these abilities influences individual variation in social relationships. We
      then consider the evolutionary consequences of the interaction between sociality
      and cognitive ability to address whether bi-directional relationships exist
      between the two, such that cognition can both shape and be shaped by social
      interactions and the social environment. In doing so, we suggest that social
      network analysis is emerging as a powerful tool that can be used to test for
      directional causal relationships between sociality and cognition. Overall, our
      review highlights the importance of investigating individual variation in
      cognition to understand how it shapes the patterns of social relationships.This
      article is part of the theme issue 'Causes and consequences of individual
      differences in cognitive abilities'.

PMID- 30104438
TI  - Linking cognition with fitness in a wild primate: fitness correlates of problem
      solving performance and spatial learning ability.
AB  - Linking the cognitive performance of wild animals with fitness consequences is
      crucial for understanding evolutionary processes that shape individual variation
      in cognition. However, the few studies that have examined these links revealed
      differing relationships between various cognitive performance measures and
      fitness proxies. To contribute additional comparative data to this body of
      research, we linked individual performance during repeated problem-solving and
      spatial learning ability in a maze with body condition and survival in wild grey
      mouse lemurs (Microcebus murinus). All four variables exhibited substantial inter
      individual variation. Solving efficiency in the problem-solving task, but not
      spatial learning performance, predicted the magnitude of change in body condition
      after the harsh dry season, indicating that the ability to quickly apply a newly
      discovered motor technique might also facilitate exploitation of new, natural
      food resources. Survival was not linked with performance in both tasks, however,
      suggesting that mouse lemurs' survival might not depend on the cognitive
      performances addressed here. Our study is the first linking cognition with
      fitness proxies in a wild primate species, and our discussion highlights the
      importance and challenges of accounting for a species' life history and ecology
      in choosing meaningful cognitive and fitness variables for a study in the
      wild.This article is part of the theme issue 'Causes and consequences of
      individual differences in cognitive abilities'.

PMID- 30104440
TI  - Penetration, distribution and brain toxicity of titanium nanoparticles in
      rodents' body: a review.
AB  - Titanium dioxide (TiO2) has been vastly used commercially, especially as white
      pigment in paints, colorants, plastics, coatings, cosmetics. Certain industrial
      uses TiO2 in diameter <100 nm. There are three common exposure routes for TiO2:
      (i) inhalation exposure, (ii) exposure via gastrointestinal tract, (iii) dermal
      exposure. Inhalation and gastrointestinal exposure appear to be the most probable
      ways of exposure, although nanoparticle (NP) penetration is limited. However, the
      penetration rate may increase substantially when the tissue is impaired. When
      TiO2 NPs migrate into the circulatory system, they can be distributed into all
      tissues including brain. In brain, TiO2 lead to oxidative stress mediated by the
      microglia phagocytic cells which respond to TiO2 NPs by the production and
      release of superoxide radicals that convert to multiple reactive oxygen species
      (ROS). The ROS production may also cause the damage of blood-brain barrier which
      then becomes more permeable for NPs. Moreover, several studies have showed neuron
      degradation and the impairment of spatial recognition memory and learning
      abilities in laboratory rodent exposed to TiO2 NPs.

PMID- 30104439
TI  - The quick are the dead: pheasants that are slow to reverse a learned association
      survive for longer in the wild.
AB  - Cognitive abilities probably evolve through natural selection if they provide
      individuals with fitness benefits. A growing number of studies demonstrate a
      positive relationship between performance in psychometric tasks and (proxy)
      measures of fitness. We assayed the performance of 154 common pheasant (Phasianus
      colchicus) chicks on tests of acquisition and reversal learning, using a
      different set of chicks and different set of cue types (spatial location and
      colour) in each of two years and then followed their fates after release into the
      wild. Across all birds, individuals that were slow to reverse previously learned
      associations were more likely to survive to four months old. For heavy birds,
      individuals that rapidly acquired an association had improved survival to four
      months, whereas for light birds, slow acquirers were more likely to be alive.
      Slow reversers also exhibited less exploratory behaviour in assays when five
      weeks old. Fast acquirers visited more artificial feeders after release. In
      contrast to most other studies, we showed that apparently 'poor' cognitive
      performance (slow reversal speed suggesting low behavioural flexibility)
      correlates with fitness benefits in at least some circumstances. This correlation
      suggests a novel mechanism by which continued exaggeration of cognitive abilities
      may be constrained.This article is part of the theme issue 'Causes and
      consequences of individual differences in cognitive abilities'.

PMID- 30104441
TI  - Brief overview of the application of silver nanoparticles to improve growth of
      crop plants.
AB  - With the advancement in nanotechnology, nanoparticles are reported to have
      applications in various fields. Their positive role in the environment,
      especially in plant ecosystem, is extensively studied nowadays. Among the metal
      nanoparticles, the silver nanoparticles (AgNP) are receiving special attention
      because of their ability to increase the growth and yield in many crops. Although
      many studies are found containing toxic effects of AgNPs the perspective of the
      present review is to collect the information about their positive role in growth
      and yield enhancement of crops. During this brief overview, many important crop
      plants are found to have a positive response towards the application of AgNPs.
      The appropriate elucidation of physiological, biochemical and molecular mechanism
      of nanoparticles in plant leads to better plant growth and development. It is
      concluded from this review that cautious and sensible use of nanotechnology can
      warrant food security through boosting agricultural production.

PMID- 30104442
TI  - Impact of Zinc oxide nanoparticles on eggplant (S. melongena): studies on growth
      and the accumulation of nanoparticles.
AB  - The increasing use of nanoparticles and their occurrence in the environment has
      made it imperative to elucidate their impact on the environment. Although several
      studies have advanced the authors' understanding of nanoparticle-plant
      interactions, their knowledge of the exposure of plants to nanoparticles and
      their effects on edible crop plants remain meager and is often paradoxical. The
      aim of this study was to increase their knowledge on the effect of zinc oxide
      (ZnO) nanoparticles on eggplant seed germination and seedling growth. ZnO
      nanoparticles had a negative effect on the growth of eggplant in plant tissue
      culture conditions, as the growth of seedlings decreased with the increase in the
      concentration of ZnO nanoparticles. In contrast, ZnO nanoparticles enhanced
      eggplant growth under greenhouse conditions. The accumulation of ZnO
      nanoparticles in various parts of eggplant was observed through scanning electron
      microscopy of both plant tissue-culture and greenhouse-raised eggplant seedlings.
      To the best of their knowledge, this is the first study to report on ZnO
      nanoparticle accumulation in eggplant and its effect on seed germination and
      seedling growth.

PMID- 30104443
TI  - Electrophoretic deposition of hydroxyapatite-shrimp crusts nanocomposite thin
      films for bone implant studies.
AB  - Hydroxyapatite-shrimp crusts nanocomposite thin films were deposited on titanium
      substrates by electrophoretic technique, under different preparation conditions,
      for bone implant applications. Fourier transform infrared spectrometer, atomic
      force microscope, X-ray diffraction (XRD), optical microscope, and scanning
      electron microscope were employed to characterise the synthesised films. Vickers'
      micro-hardness measurements revealed a value of 502 HV for the hydroxyapatite
      films and 314.55 HV for the nanocomposite films. XRD results confirmed the
      polycrystalline nature of the hydroxyapatite and hydroxyapatite-shrimp
      nanocomposite films. The in-vitro bioactivity test of the synthesised films in
      simulated body fluid showed very low dissolution rate. Antibacterial activity of
      synthesised films was investigated against E. coli bacteria.

PMID- 30104444
TI  - Synthesis and characterisation of silver nanoparticles using leaf extract of
      Artemisia afra and their in vitro antimicrobial and antioxidant activities.
AB  - In this study, the conversion of silver ions into ~30.74 nm sized silver
      nanoparticles (AgNPs) was achieved in 30 min at a reaction temperature of 80-90
      degrees C in aqueous leaf extract of Artemisia afra. The synthesised AgNPs showed
      surface plasmon resonance in the range of 423-438 nm. Spherical and face-centred
      cubic nanoparticles were confirmed by transmission electron microscope (TEM) and
      X-ray diffraction (XRD) analysis, respectively. Fourier transform infra-red
      (FTIR) results indicated that the obtained nanoparticles were stabilised and
      capped through the carbonyl and carboxylate ion groups possibly from flavonoids,
      terpenoids, phenolics and esters content of the extracts. In addition, the AgNPs
      were assessed for their biological potentials against some microbes and, also,
      their free radical scavenging ability was established. The AgNPs exhibited
      interesting antimicrobial and antioxidant properties better than the aqueous
      extract of A. afra.

PMID- 30104445
TI  - Evaluation of potential anti-cancer activity of cationic liposomal nanoformulated
      Lycopodium clavatum in colon cancer cells.
AB  - Research dealing with early diagnosis and efficient treatment in colon cancer to
      improve patient's survival is still under investigation. Chemotherapeutic agent
      result in high systemic toxicity due to their non-specific actions on DNA repair
      and/or cell replication. Traditional medicine such as Lycopodium clavatum (LC)
      has been claimed to have therapeutic potentials against cancer. The present study
      focuses on targeted drug delivery of cationic liposomal nanoformulated LC (CL-LC)
      in colon cancer cells (HCT15) and comparing the efficacy with an anti-colon
      cancer drug, 7-ethyl-10-hydroxy-camptothecin (SN38) along with its nanoformulated
      form (CL-SN38). The colloidal suspension of LC was made using thin film hydration
      method. The drugs were characterised using ultraviolet, dynamic light scattering,
      scanning electron microscopy, energy, dispersive X-ray spectroscopy. Invitro drug
      release showed kinetics of 49 and 89% of SN38 and LC, whereas CL-SN38 and CL-LC
      showed 73 and 74% of sustained drug release, respectively. Studies on
      morphological changes, cell viability, cytotoxicity, apoptosis, cancer-associated
      gene expression analysis of Bcl-2, Bax, p53 by real-time polymerase chain
      reaction and western blot analysis of Bad and p53 protein were performed.
      Nanoformulated LC significantly inhibited growth and increased the apoptosis of
      colon cancer cells indicating its potential anti-cancer activity against colon
      cancer cells.

PMID- 30104446
TI  - Differential antibacterial response exhibited by graphene nanosheets toward gram
      positive bacterium Staphylococcus aureus.
AB  - Two different morphological forms of graphene nanosheets: improved reduced
      graphene oxide (IRGO) and modified reduced GO (rGO) (MRGO) have been synthesised
      by improved and modified methods, respectively. Physical characterisations of
      these graphene nanosheets were carried out using X-ray diffraction, Fourier
      transform infrared spectroscopy, and Raman spectroscopy. Colloidal stability of
      these nanosheets toward a selected bacterium (e.g. Staphylococcus aureus) was
      ascertained by zeta potential. In the present study, the authors for the first
      time made an attempt to study and compare the potentialities of these two
      different forms of graphene nanosheets as efficient bactericidal agents. Field
      emission scanning electron microscopy and TEM with energy dispersive X-ray
      spectroscopy (EDAX) studies of IRGO and MRGO have been carried out to explore
      their underlying mechanism of antibacterial responses through physical as well as
      chemical interactions with the selected bacterial species.

PMID- 30104447
TI  - Biosynthesis of Ag, Se, and ZnO nanoparticles with antimicrobial activities
      against resistant pathogens using waste isolate Streptomyces enissocaesilis.
AB  - Nanoparticles (NPs) are gaining special interest due to their recent applications
      as antimicrobial agents to defeat the massive threat of resistant pathogens. This
      study focused on the utilisation of Streptomyces isolate S12 purified from waste
      discharge soil in the biological synthesis of silver (Ag), selenium (Se), and
      zinc oxide (ZnO) NPs. The isolate S12 was related to Streptomyces enissocaesilis
      according to 16S rRNA sequence analysis, morphological characteristics, and
      biochemical reactions. The cell-free supernatant has been used for the synthesis
      of Ag, Se, and ZnO NPs. The synthesised NPs were characterised using ultraviolet
      visible spectroscopy, dynamic light scattering (DLS), transmission electron
      microscopy, and Fourier transform infrared spectroscopy. The biogenic NPs were
      evaluated for antimicrobial effects against different Gram-positive and Gram
      negative resistant isolates using the broth microdilution method. They showed
      antibacterial effect against standard and resistant isolates; Bacillus cereus,
      Staphylococcus aureus ATCC 29213, S. aureus S1.1, methicillin resistant S. aureus
      (MRSA 303, 402 and 807), Escherichia coli ATCC 12435, E. coli E7, Klebsiella
      pneumoniae ATCC 51503, K. pneumoniae K5, K112, Pseudomonas aeruginosa PAO1, and
      P. aeruginosa P8. This study showed the green synthesis of various NPs using
      Streptomyces isolate S12 which demonstrated diverse activities against multi-drug
      resistant isolates.

PMID- 30104448
TI  - One-pot green synthesis and structural characterisation of silver nanoparticles
      using aqueous leaves extract of Carissa carandas: antioxidant, anticancer and
      antibacterial activities.
AB  - Facile green synthesis of silver nanoparticles (AgNPs) using an aqueous extract
      of Carissa carandas (C. carandas) leaves was studied. Fabrication of AgNPs was
      confirmed by the UV-visible spectroscopy which gives absorption maxima at 420 nm.
      C. carandas leaves are the rich source of the bioactive molecules, acts as a
      reducing and stabilising agent in AgNPs, confirmed by Fourier transforms infrared
      spectroscopy. The field emission scanning electron microscope revealed the
      spherical shape of biosynthesised AgNPs. A distinctive peak of silver at 3 keV
      was determined by energy dispersive X-ray spectroscopy. X-ray diffraction showed
      the facecentred cubic structure of biosynthesised AgNPs and thermal stability was
      confirmed by the thermogravimetric analysis. Total flavonoid and total phenolic
      contents were evaluated in biosynthesised AgNPs. Biosynthesised AgNPs showed free
      radical scavenging activities against 2, 2-diphenyl-1-picrylhydrazyl test and
      ferric reducing antioxidant power assay. In vitro cytotoxicity against hepatic
      cell lines (HUH-7) and renal cell lines (HEK-293) were also assessed. Finally,
      biosynthesised AgNPs were scrutinised for their antibacterial activity against
      methicillin-resistant Staphylococcus aureus, Shigella sonnei, Shigella boydii and
      Salmonella typhimurium. This study demonstrated the biofabrication of AgNPs by
      using C. carandas leaves extract and a potential in vitro biological application
      as antioxidant, anticancer and antibacterial agents.

PMID- 30104450
TI  - Biosynthesised AgCl NPs using Bacillus sp. 1/11 and evaluation of their cytotoxic
      activity and antibacterial and antibiofilm effects on multi-drug resistant
      bacteria.
AB  - Silver nanoparticles (AgNPs) have attracted the attention of researchers due to
      their properties. Biological synthesis of AgNPs is eco-friendly and cost
      effective preferred to physical and chemical methods, which utilize
      environmentally harmful agents and large amounts of energy. Microorganisms have
      been explored as potential biofactories to synthesize AgNPs. Bacterial NP
      synthesis is affected by Ag salt concentration, pH, temperature and bacterial
      species. In this study, Bacillus spp., isolated from soil, were screened for AgNP
      synthesis at pH 12 with 5 mM Ag nitrate (AgNO3) final concentration at room
      temperature. The isolate with fastest color change and the best ultraviolet
      visible spectrum in width and height were chosen as premier one. AgNO3 and
      citrate salts were compared in terms of their influence on NP synthesis.
      Spherical Ag chloride (AgCl) NPs with a size range of 35-40 nm were synthesized
      in 1.5 mM Ag citrate solution. Fourier transform infrared analysis demonstrated
      that protein and carbohydrates were capping agents for NPs. In this study,
      antimicrobial and antitumor properties of the AgNP were investigated. The
      resulting AgCl NPs had bacteriostatic activity against four standard spp. And
      multi-drug resistant strain of Pseudomonas aeruginosa. These NPs are also
      cytotoxic to cancer cell lines MCF-7, U87MG and T293.

PMID- 30104449
TI  - Preparation and in vitro evaluation of novel cross-linked chondroitin sulphate
      nanoparticles by aluminium ions for encapsulation of green tea flavonoids.
AB  - Chondroitin sulphate is a sulphated glycosaminoglycan biopolymer composed over
      100 individual sugars. Chondroitin sulphate nanoparticles (NPs) loaded with
      catechin were prepared by an ionic gelation method using AlCl3 and optimised for
      polymer and cross-linking agent concentration, curing time and stirring speed.
      Zeta potential, particle size, loading efficiency, and release efficiency over 24
      h (RE24%) were evaluated. The surface morphology of NPs was investigated by
      scanning electron microscopy and their thermal behaviour by differential scanning
      calorimetric. Antioxidant effect of NPs was determined by chelating activity of
      iron ions. The cell viability of mesenchymal stem cells was determined by 3-[4, 5
      dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide assay and the
      calcification of osteoblasts was studied by Alizarin red staining. The optimised
      NPs showed particle size of 176 nm, zeta potential of -20.8 mV, loading
      efficiency of 93.3% and RE24% of 80.6%. The chatechin loaded chondroitin sulphate
      NPs showed 70-fold more antioxidant activity, 3-fold proliferation effect and
      higher calcium precipitation in osteoblasts than free catechin.

PMID- 30104451
TI  - CL sensitisation of tris-(bipyridyl) ruthenium (II) - cerium (IV) reaction system
      by AgNPs for determination of GFX.
AB  - The flow injection combined with tris-(bipyridyl) ruthenium (II)-cerium (IV)
      chemiluminescence (CL) method based on the sensitisation of silver nanoparticles
      (AgNPs) has been established for the quantitative analysis of gatifloxacin (GFX).
      AgNPs were synthesised using the reaction between ammonia gas and silver nitrate
      solution and was used to increase the CL intensity of the proposed system. The
      enhancement of CL intensity was linear with the concentration of GFX added.
      Effects of different experimental parameters were studied. Under the optimal
      conditions, the linear relationship was established between the concentration
      range of 1.4 * 10-10-4.5 * 10-8 M, with the correlation coefficient (r2) 02E9999.
      The limit of detection was found to be 4.6 * 10-11 M. The relative standard
      deviation obtained was 3.2% for six replicate measurements of GFX (1.2 * 10-9 M).
      The proposed CL method was applied to the commercial drug and the result was in
      agreement with the labelled amount. The technique was further adopted to the
      analysis of GFX in spiked urine samples. Negligible interference was found
      (variation in CL intensity <5%) from a few common foreign excipients applied in
      preparation of pharmaceutical drug. The comparative results with a few reported
      methods indicates that the proposed method is more sensitive than other methods..

PMID- 30104452
TI  - Preparation of silver iodide nanoparticles using laser ablation in liquid for
      antibacterial applications.
AB  - In this study, the authors reported the first synthesis process of silver iodide
      (AgI) nanoparticles (NPs) by pulsed laser ablation of the AgI target in deionised
      distilled water. The optical and structural properties of AgI NPs were
      investigated by using UV-vis absorption, X-ray diffraction, scanning electron
      microscope (SEM), energy dispersive X-ray, Fourier transform infrared
      spectroscopy, and transmission electron microscope (TEM). The optical data showed
      the presence of plasmon peak at 434 nm and the optical bandgap was found to be
      2.6 eV at room temperature. SEM results confirm the agglomeration and aggregation
      of synthesised AgI NPs. TEM investigation showed that AgI NPs have a spherical
      shape and the average particle size was around 20 nm. The particle size
      distribution was the Gaussian type. The results showed that the synthesised AgI
      NPs have antibacterial activities against both bacterial strains and the
      activities were more potent against gram-negative bacteria.

PMID- 30104453
TI  - Synthesis of Co3O4/graphene nanocomposite using paraffin wax for adsorption of
      methyl violet in water.
AB  - This study discusses the use of Co3O4 impregnated graphene (CoOIG) as an
      efficient adsorbent for the removal of methyl violet (MV) dye from wastewater.
      CoOIG nanocomposites have been prepared by pyrolyzing paraffin wax with cobalt
      acetate. The synthesised nanocomposite was characterised by X-ray diffraction,
      field emission scanning electron microscope, transmission electron microscope,
      Fourier transform infrared spectroscope, Raman spectroscopy, and Brunauer-Emmett
      Teller isotherm studies. The above studies indicate that the composites have
      cobalt oxide nanoparticles of size 51-58 nm embedded in the graphene
      nanoparticles. The adsorption studies were conducted with various parameters, pH,
      temperature and initial dye concentration, adsorbent dosage and contact time by
      the batch method. The adsorption of MV dye by the adsorbent CoOIG was about 90%
      initially at 15 min and 98% dye removal at pH 5. The data were fitted in
      Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich and Sips isotherm models.
      Various thermodynamic parameters like Gibbs free energy, enthalpy, and entropy of
      the on-going adsorption process have also been calculated.

PMID- 30104454
TI  - Efavirenz oral delivery via lipid nanocapsules: formulation, optimisation, and ex
      vivo gut permeation study.
AB  - Present investigation aimed to prepare, optimise, and characterise lipid
      nanocapsules (LNCs) for improving the solubility and bioavailability of efavirenz
      (EFV). EFV-loaded LNCs were prepared by the phase-inversion temperature method
      and the influence of various formulation variables was assessed using Box-Behnken
      design. The prepared formulations were characterised for particle size,
      polydispersity index (PdI), zeta potential, encapsulation efficiency (EE), and
      release efficiency (RE). The biocompatibility of optimised formulation on Caco-2
      cells was determined using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium
      bromide assay. Then, it was subjected to ex-vivo permeation using rat intestine.
      EFV-loaded LNCs were found to be spherical shape in the range of 20-100 nm with
      EE of 82-97%. The best results obtained from LNCs prepared by 17.5% labrafac and
      10% solutol HS15 when the volume ratio of the diluting aqueous phase to the
      initial emulsion was 3.5. The mean particle size, zeta potential, PdI, EE, drug
      loading%, and RE during 144 h of optimised formulation were confirmed to 60.71
      nm, -35.93 mV, 0.09, 92.60, 7.39 and 55.96%, respectively. Optimised LNCs
      increased the ex vivo intestinal permeation of EFV when compared with drug
      suspension. Thus, LNCs could be promising for improved oral delivery of EFV.

PMID- 30104455
TI  - Fabrication of cellulose nanoparticles through electrospraying.
AB  - This study reports the fabrication of cellulose nanoparticles through
      electrospraying the solution of cellulose in N,N-dimethylacetamide/lithium
      chloride solvent as well as investigating the effect of electrospraying
      conditions and molecular weight on the average size of electrosprayed
      nanoparticles. Electrospraying of cellulose was carried out with the following
      range for each factor, namely concentration = 1-3 wt%, voltage = 15-23 kV, nozzle
      collector distance = 10-25 cm, and feed rate = 0.03-0.0875 ml/h. The smallest
      nanoparticles had an average size of around 40 nm. Results showed that lowering
      the solution concentration and feed rate, as well as increasing the nozzle
      collector distance and applied voltage led to a decrease in the average size of
      the electrosprayed cellulose nanoparticles. Fourier transform infrared analysis
      proved that no chemical change had occurred in the cellulose structure after the
      electrospraying process. According to X-ray diffraction (XRD) results, cellulose
      nanoparticles showed a lower degree of crystallinity in comparison with the raw
      cellulose powder. XRD results also proved the absence of LiCl salt in the
      electrosprayed nanoparticles.

PMID- 30104456
TI  - Core/shell nanoassembly of amphiphilic naproxen-polyethylene glycol: synthesis,
      characterisation and evaluation as drug delivery system.
AB  - Small molecule-based amphiphiles self-assemble into nanostructures (micelles) in
      aqueous medium which are currently being explored as novel drug delivery systems.
      Here, naproxen-polyethylene glycol (N-PEG), a small molecule-derived amphiphile,
      has been synthesised, characterised and evaluated as hydrophobic drug carrier.
      1H, 13C Nuclear magnetic resonance (NMR), mass spectrometry (MS) and Fourier
      transform infrared spectroscopy (FTIR) confirmed the formation of N-PEG and
      dynamic light scattering (DLS) revealed the formation of nano-sized structures of
      ~228 nm. Transmission electron microscope (TEM) analysis showed aggregation
      behaviour of the structures with average size of ~230 nm. Biodegradability aspect
      of the micellar-structured N-PEG was demonstrated by lipase-mediated degradation
      studies using DLS and TEM. High encapsulation efficiency followed by release in a
      sustained manner of a well-known anticancer drug, doxorubicin, demonstrated the
      feasibility of the new drug delivery system. These results advocate the promising
      potential of N-PEG micelles as efficient drug delivery system for specific
      delivery to cancerous cells in vitro and in vivo.

PMID- 30104457
TI  - Optimisation of green synthesis of MnO nanoparticles via utilising response
      surface methodology.
AB  - This study concerns the optimisation of green synthesis of manganese oxide
      nanoparticles (MnO NPs) with Dittrichia graveolens (L.) extract via response
      surface methodology (RSM). Central composite design was used to evaluate the
      effect of pH, time, and the extract to the metal ratio on the synthesised
      nanoparticles (NPs). Nine runs were designed to investigate the effect of each
      parameter while NPs were synthesised under different conditions. Considering the
      p-values (p-value < 0.05), it is indicated that the extract to the metal ratio
      was the most effective parameter. The synthesised NPs were characterised using UV
      vis. Synthesis of the NPs by polyphenolic compounds of green reducing agent and
      their stabilisation by curcumin was confirmed by Fourier transform infrared
      spectra and the surface morphology of the spherical MnO NPs was studied by field
      emission scanning electron microscopy and transmission electron microscope
      techniques. The present researchers claimed the optimal condition as follows:
      time = 56.7 min, pH = 7.2, and the extract to the metal ratio = 87.9 v/v. MnO NPs
      at optimum condition were then employed for degradation of industrial dyes and
      they showed high dye degradation activity against Rhodamine B and light green
      dye. The average size of the synthesised MnO NPs at optimal condition was claimed
      to be nearly 38 nm.

PMID- 30104458
TI  - Biological synthesis and characterisation of silver nanoparticles using
      Pseudomonas geniculata H10 for pharmaceutical activity.
AB  - In the present study, silver nanoparticles (SNPs) were synthesised for the first
      time using Pseudomonas geniculata H10 as reducing and stabilising agents. The
      synthesis of SNPs was the maximum when the culture supernatant was treated with
      2.5 mM AgNO3 at pH 7 and 40 degrees C for 10 h. The SNPs were characterised by
      field emission scanning electron microscopy-energy-dispersive spectroscopy,
      transmission electron microscopy, dynamic light scattering, X-ray diffraction and
      UV-vis spectroscopy. Fourier transform infrared spectroscopy indicated the
      presence of proteins, suggesting they may have been responsible for the reduction
      and acted as capping agents. The SNPs displayed 1,1-diphenyl-2-picrylhydrazyl
      (IC50 = 28.301 MUg/ml) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulphonate
      (IC50 = 27.076 MUg/ml) radical scavenging activities. The SNPs exhibited a broad
      antimicrobial spectrum against several human pathogenic Gram-positive and Gram
      negative bacteria and Candida albicans. The antimicrobial action of SNPs was due
      to cell deformation resulting in cytoplasmic leakage and subsequent lysis. The
      authors' results indicate P. geniculata H10 could be used to produce
      antimicrobial SNPs in a facile, non-toxic, cost-effective manner, and that these
      SNPs can be used as effective growth inhibitors in various microorganisms, making
      them applicable to various biomedical and environmental systems. As far as the
      authors are aware, this study is the first to describe the potential biomedical
      applications of SNPs synthesised using P. geniculata.

PMID- 30104460
TI  - Laser-induced heating for in situ DNA replication and detection in microchannels.
AB  - This study proposes a method for in situ local deoxyribonucleic acid (DNA)
      replication and detection in a long DNA strand through laser-induced heating and
      strong avidin-biotin binding. To achieve the target DNA replication,
      dielectrophoresis was generated to stretch and immobilise DNA strands on both
      ends of the electrode. Subsequently, local DNA sequences were replicated using
      thermal cycles generated by laser-induced heating. Replicated double-stranded DNA
      products were captured in situ on a solid surface and detected using the
      fluorescence intensity of quantum dots (Qdots). The results revealed that after
      six laser-induced thermal cycles, the replicated local DNA sequence could be
      detected by analysing the difference between Qdot fluorescent intensity before
      and after replication. The proposed method is expected to improve the efficiency
      of biosample gene sequence analysis.

PMID- 30104459
TI  - FSE-Ag complex NS: preparation and evaluation of antibacterial activity.
AB  - Silver (Ag) complexes of drugs and their nanosystems have great potential as
      antibacterials. Recently, an Ag complex of furosemide (Ag-FSE) has shown to be a
      promising antimicrobial. However, poor solubility of Ag-FSE could hamper its
      introduction into clinics. Therefore, the authors developed a nanosuspension of
      Ag-FSE (Ag-FSE_NS) for its solubility and antibacterial activity enhancement. The
      aim of this study was to introduce a novel nanoantibiotic with enhanced
      antibacterial efficacy. Ag-FSE_NS was prepared by precipitation-ultrasonication
      technique. Size, polydispersity index (PI) and zeta potential (ZP) of prepared Ag
      FSE_NS were measured by dynamic light scattering, whereas surface morphology was
      determined using scanning electron microscopy (SEM). In vitro antibacterial
      activity was evaluated against Staphylococcus aureus, Escherichia coli and
      Pseudomonas aeruginosa using broth microdilution method. Size, PI and ZP of
      optimised Ag-FSE_NS1 were 191.2 +/- 19.34 nm, 0.465 +/- 0.059 and -55.7 +/- 8.18
      mV, respectively. SEM revealed that Ag-FSE_NS1 particles were rod or needle-like
      with smooth surfaces. Saturation solubility of Ag-FSE in NS increased eight-fold
      than pure Ag-FSE. Ag-FSE_NS1 exhibited two-fold and eight-fold enhancements in
      activity against E. coli and S. aureus, respectively. The results obtained showed
      that developed Ag-FSE_NS1 holds a promise as a topical antibacterial.

PMID- 30104461
TI  - Synthesis and characterisation of liposomal doxorubicin with loaded gold
      nanoparticles.
AB  - Developing nanostructures for cancer treatment is growing significantly.
      Liposomal doxorubicin is a drug that is used in the clinic and represents a lot
      of benefits over doxorubicin. The development of multifunctional liposomes with
      different cancer treatment capability enables broader applications of doxorubicin
      chemotherapy. Many efforts were carried to prepare more effective liposomal
      formulation through loading gold nanoparticles (GNPs) in the formulation. Here,
      GNPs with an average size of 6 nm were loaded in liposomal formulation alongside
      doxorubicin. The hydrodynamic diameter of final formulation was 177.3 +/- 33.9 nm
      that in comparison with liposomes without GNPs (112.5 +/- 10.3 nm), GNPs-loaded
      liposomes showed the bigger hydrodynamic diameter. GNPs-loaded liposomes are
      slightly positively charged (4.4 +/- 1.1 mV), while liposomes without loading the
      GNPs were negatively charged (-18.5 +/- 1.6 mV). Doxorubicin was loaded in this
      formulation through active loading technique. Doxorubicin loading efficiency in
      gold-loaded liposomes is slightly lesser than liposomes without GNPs, but still
      considerably high in comparison to passive loading techniques.

PMID- 30104462
TI  - Eco-friendly synthesis of silver and gold nanoparticles with enhanced
      antimicrobial, antioxidant, and catalytic activities.
AB  - The present work is emphasised on the bio-fabrication of silver and gold
      nanoparticles in a single step by a microwave-assisted method using the leaf
      extract of Synedrella nodiflora as both reducing and stabilising agent. The
      synthesised nanoparticles are highly stable and show surface plasmon resonance
      peak at 413 and 535 nm, respectively, for silver and gold nanoparticles in UV-Vis
      spectrum. The functional group responsible for the reduction of metal ions were
      obtained from Fourier transform infrared spectroscopy. The crystalline nature of
      nanoparticles with face-centred cubic geometry was confirmed by the X-ray
      diffraction and selected area electron diffraction patterns. The morphology and
      sizes of the silver and gold nanoparticles were obtained from transmission
      electron microscopy images. The nanoparticles exhibit effective antimicrobial
      activities against various pathogenic strains. These antimicrobial properties
      were analysed by employing agar well diffusion method. The nanoparticles show
      significant antioxidant properties, and it was determined using 2, 2-diphenyl-1
      picrylhydrazyl assay. The nanoparticles also show potent catalytic activity in
      the degradation of anthropogenic pollutant dyes Congo red and eosin Y by excess
      NaBH4. Thus, the current study demonstrates the potential use of S. nodiflora as
      a reducing and stabilising agent for the synthesis of silver and gold
      nanoparticles and their relevance in the field of biomedicine and catalysis.

PMID- 30104463
TI  - Fungal xylanases-mediated synthesis of silver nanoparticles for catalytic and
      biomedical applications.
AB  - Green synthesis of nanoparticles has fuelled the use of biomaterials to
      synthesise a variety of metallic nanoparticles. The current study investigates
      the use of xylanases of Aspergillus niger L3 (NEA) and Trichoderma
      longibrachiatum L2 (TEA) to synthesise silver nanoparticles (AgNPs).
      Characterisation of AgNPs was carried out using UV-Vis spectroscopy, Fourier
      transform infrared spectroscopy (FTIR), and transmission electron microscopy,
      while their effectiveness as antimicrobial, antioxidant, catalytic,
      anticoagulant, and thrombolytic agents were determined. The colloidal AgNPs was
      brownish with surface plasmon resonance at 402.5 and 410 nm for NEA-AgNPs and TEA
      AgNPs, respectively; while FTIR indicated that protein molecules were responsible
      for the capping and stabilisation of the nanoparticles. The spherical
      nanoparticles had size of 15.21-77.49 nm. The nanoparticles significantly
      inhibited the growth of tested bacteria (63.20-88.10%) and fungi (82.20-86.10%),
      and also scavenged DPPH (37.48-79.42%) and hydrogen peroxide (20.50-96.50%). In
      addition, the AgNPs degraded malachite green (78.97%) and methylene blue
      (25.30%). Furthermore, the AgNPs displayed excellent anticoagulant and
      thrombolytic activities using human blood. This study has demonstrated the
      potential of xylanases to synthesise AgNPs which is to the best of our knowledge
      the first record of such. The present study underscores the relevance of
      xylanases in nanobiotechnology.

PMID- 30104464
TI  - Nanohexaconazole: synthesis, characterisation and efficacy of a novel fungicidal
      nanodispersion.
AB  - Here, the authors describe a simple method to formulate the nanodispersion of
      hexaconazole (hexa); henceforth, referred to as nanohexaconazole (N-hexa) that is
      water soluble and effective against several species of Aspergillus. Size and
      shape of the prepared nanocomposite was determined with high-resolution
      transmission electron microscopy and field-emission scanning electron microscopy.
      Nanohexaconazole structure was further confirmed by Fourier-transform infrared
      spectroscopy and gas chromatography-mass spectrometry. The antifungal efficacy of
      nanohexaconazole (N-hexa) was studied in vitro, compared with micronised
      hexaconazole (M-hexa) at different doses (5 ppm, 10 ppm and control) against two
      food pathogenic fungi: Aspergillus niger (MTCC 282, MTCC 2196 and BDS 113) and
      Aspergillus fumigatus through poisoned food technique. A dose-dependent
      significant growth inhibition was observed in nanohexaconazole (N-hexa) treated
      fungal sample compared with that of micronised hexaconazole (M-hexa).
      Micrographic studies for the morphological analysis of control and
      nanohexaconazole (N-hexa) treated fungal samples were done, exhibited an
      alternation in fungal morphology. Results showed that nanohexaconazole (N-hexa)
      is more efficacious than commercially available micronised hexaconazole (M-hexa).
      In future nanohexaconazole (N-hexa) could be a possible candidate for modern
      medical science and also reduce damage to the environment from injudicious use of
      pesticides.

PMID- 30104465
TI  - The ATR-Activation Domain of TopBP1 Is Required for the Suppression of Origin
      Firing during the S Phase.
AB  - The mammalian DNA replication program is controlled at two phases, the licensing
      of potential origins of DNA replication in early gap 1 (G1), and the selective
      firing of a subset of licenced origins in the synthesis (S) phase. Upon entry
      into the S phase, serine/threonine-protein kinase ATR (ATR) is required for
      successful completion of the DNA replication program by limiting unnecessary
      dormant origin activation. Equally important is its activator, DNA topoisomerase
      2-binding protein 1 (TopBP1), which is also required for the initiation of DNA
      replication after a rise in S-phase kinase levels. However, it is unknown how the
      ATR activation domain of TopBP1 affects DNA replication dynamics. Using human
      cells conditionally expressing a TopBP1 mutant deficient for ATR activation, we
      show that functional TopBP1 is required in suppressing local dormant origin
      activation. Our results demonstrate a regulatory role for TopBP1 in the local
      balancing of replication fork firing within the S phase.

PMID- 30104466
TI  - Development of Antibacterial and Antifungal Triazole Chromium(III) and Cobalt(II)
      Complexes: Synthesis and Biological Activity Evaluations.
AB  - In this work, six complexes (2-7) of Cr(III) and Co(II) transition metals with
      triazole ligands were synthesized and characterized. In addition, a new ligand,
      3,5-bis(1,2,4-triazol-1-ylmethyl)toluene (1), was synthesized and full
      characterized. The complexes were obtained as air-stable solids and characterized
      by melting point, electrical conductivity, thermogravimetric analysis, and Raman,
      infrared and ultraviolet/visible spectroscopy. The analyses and spectral data
      showed that complexes 3-7 had 1:1 (M:L) stoichiometries and octahedral
      geometries, while 2 had a 1:2 (M:L) ratio, which was supported by DFT
      calculations. The complexes and their respective ligands were evaluated against
      bacterial and fungal strains with clinical relevance. All the complexes showed
      higher antibacterial and antifungal activities than the free ligands. The
      complexes were more active against fungi than against bacteria. The activities of
      the chromium complexes against Candida tropicalis are of great interest, as they
      showed minimum inhibitory concentration 50 (MIC50) values between 7.8 and 15.6
      MUg mL-1. Complexes 5 and 6 showed little effect on Vero cells, indicating that
      they are not cytotoxic. These results can provide an important platform for the
      design of new compounds with antibacterial and antifungal activities.

PMID- 30104467
TI  - Development and Characterization of High-Throughput EST-Based SSR Markers for
      Pogostemon cablin Using Transcriptome Sequencing.
AB  - Simple sequence repeats (SSRs) or microsatellite markers derived from expressed
      sequence tags (ESTs) are routinely used for molecular assisted-selection
      breeding, comparative genomic analysis, and genetic diversity studies. In this
      study, we investigated 54,546 ESTs for the identification and development of SSR
      markers in Pogostemon cablin (Patchouli). In total, 1219 SSRs were identified
      from 1144 SSR-containing ESTs. Trinucleotides (80.8%) were the most abundant
      SSRs, followed by di- (10.8%), mono- (7.1%), and hexa-nucleotides (1.3%). The top
      six motifs were CCG/CGG (15.3%), AAG/CTT (15.0%), ACC/GGT (13.5%), AGG/CCT
      (12.4%), ATC/ATG (9.9%), and AG/CT (9.8%). On the basis of these SSR-containing
      ESTs, a total of 192 primer pairs were randomly designed and used for
      polymorphism analysis in 38 accessions collected from different geographical
      regions of Guangdong, China. Of the SSR markers, 45 were polymorphic and had
      allele variations from two to four. Furthermore, a transferability analysis of
      these primer pairs revealed a 10-40% cross-species transferability in 10 related
      species. This report is the first comprehensive study on the development and
      analysis of a large set of SSR markers in P. cablin. These markers have the
      potential to be used in quantitative trait loci mapping, genetic diversity
      studies, and the fingerprinting of cultivars of P. cablin.

PMID- 30104468
TI  - Effect of Ammonium Halide Additives on the Performance of Methyl Amine Based
      Perovskite Solar Cells.
AB  - CH3NH3PbI3-xClx species were fabricated as light-absorbing layers for perovskite
      solar cells (PSCs), by employing NH4I, NH4Br, and NH4Cl as additives via
      annealing at 100  degrees C for different times. Solutions containing CH3NH3I,
      PbI2, and PbCl2 (4:1:1 molar ratio) in N,N-dimethylformamide were used to prepare
      perovskites with NH4I, NH4Br, and NH4Cl as additives, at concentrations of 0.1 M
      and 0.3 M. The additives helped increase the grain size and reduce pinholes in
      the perovskite films, as confirmed by field-emission scanning electron
      microscopy. The X-ray diffraction profiles of CH3NH3PbI3-xClx clearly showed
      peaks at 14 degrees  and 28 degrees  for the samples with additives, indicative
      of crystallinity. The best PSC performance with a power conversion efficiency of
      9.13%, was achieved using 0.1 M NH4I by annealing for 5 min, whereas the power
      conversion efficiency of the perovskite solar cells without additives was 5.40%.

PMID- 30104469
TI  - Oxidation of Cefalexin by Permanganate: Reaction Kinetics, Mechanism, and
      Residual Antibacterial Activity.
AB  - The oxidation of cefalexin (CFX), a commonly used cephalosporin antibiotic, was
      investigated by permanganate (PM) in water. Apparent second-order rate constant
      of the reaction between CFX and PM was determined to be 12.71 +/- (1.62) M-1.s-1
      at neutral pH. Lower pH was favorable for the oxidation of CFX by PM. The
      presence of Cl- and HCO3- could enhance PM-induced oxidation of CFX, whereas HA
      had negligible effect on CFX oxidation by PM. PM-induced oxidation of CFX was
      also significant in the real wastewater matrix. After addition of bisulfite (BS),
      PM-induced oxidation was significantly accelerated owing to the generation of
      Mn(III) reactive species. Product analysis indicated oxidation of CFX to three
      products, with two stereoisomeric sulfoxide products and one di-ketone product.
      The thioether sulfur and double bond on the six-membered ring were the reactive
      sites towards PM oxidation. Antibacterial activity assessment indicated that the
      activity of CFX solution was significantly reduced after PM oxidation.

PMID- 30104470
TI  - The Implications of Fragmented Genomic DNA Size Range on the Hybridization
      Efficiency in NanoGene Assay.
AB  - DNA hybridization-based assays are well known for their ability to detect and
      quantify specific bacteria. Assays that employ DNA hybridization include a
      NanoGene assay, fluorescence in situ hybridization, and microarrays. Involved in
      DNA hybridization, fragmentation of genomic DNA (gDNA) is necessary to increase
      the accessibility of the probe DNA to the target gDNA. However, there has been no
      thorough and systematic characterization of different fragmented gDNA sizes and
      their effects on hybridization efficiency. An optimum fragmented size range of
      gDNA for the NanoGene assay is hypothesized in this study. Bacterial gDNA is
      fragmented via sonication into different size ranges prior to the NanoGene assay.
      The optimum size range of gDNA is determined via the comparison of respective
      hybridization efficiencies (in the form of quantification capabilities).
      Different incubation durations are also investigated. Finally, the quantification
      capability of the fragmented (at optimum size range) and unfragmented gDNA is
      compared.

PMID- 30104471
TI  - Antibody to Marinobufagenin Reverses Placenta-Induced Fibrosis of Umbilical
      Arteries in Preeclampsia.
AB  - BACKGROUND: Previous studies implicated cardiotonic steroids, including Na/K
      ATPase inhibitor marinobufagenin (MBG), in the pathogenesis of preeclampsia (PE).
      Immunoneutralization of heightened MBG by Digibind, a digoxin antibody, reduces
      blood pressure (BP) in patients with PE, and anti-MBG monoclonal antibody lessens
      BP in a rat model of PE. Recently, we demonstrated that MBG induces fibrosis in
      cardiovascular tissues via a mechanism involving inhibition of Fli-1, a nuclear
      transcription factor and a negative regulator of collagen-1 synthesis. OBJECTIVES
      AND METHODS: We hypothesized that in PE, elevated placental MBG levels are
      associated with development of fibrosis in umbilical arteries. Eleven patients
      with PE (mean BP 124 +/- 4 mmHg; age 29 +/- 2 years; 39 weeks gest. age) and 10
      gestational age-matched normal pregnant subjects (mean BP 92 +/- 2 mmHg;
      controls) were enrolled in the clinical study. RESULTS: PE was associated with a
      higher placental (0.04 +/- 0.01 vs. 0.49 +/- 0.11 pmol/g; p < 0.01) and plasma
      MBG (0.5 +/- 0.1 vs. 1.6 +/- 0.5 nmol/L; p < 0.01), lower Na/K-ATPase activity in
      erythrocytes (2.7 +/- 0.2 vs. 1.5 +/- 0.2 umol Pi/mL/hr; p < 0.01), 9-fold
      decrease of Fli-1 level and 2.5-fold increase of collagen-1 in placentae (p <
      0.01) vs. control. Incubation of umbilical arteries from control patients with 1
      nmol/L MBG was associated with four-fold decrease in Fli-1 level and two-fold
      increase in collagen-1 level vs. those incubated with placebo (p < 0.01), i.e.,
      physiological concentration of MBG mimicked effect of PE in vitro. Collagen-1
      abundance in umbilical arteries from PE patients was 4-fold higher than in
      control arteries, and this PE-associated fibrosis was reversed by monoclonal anti
      MBG antibody ex vivo. CONCLUSION: These results demonstrate that elevated
      placental MBG level is implicated in the development of fibrosis of the placenta
      and umbilical arteries in PE.

PMID- 30104472
TI  - Oridonin Enhances Radiation-Induced Cell Death by Promoting DNA Damage in Non
      Small Cell Lung Cancer Cells.
AB  - Although many attempts have been made to improve the efficacy of radiotherapy to
      treat cancer, radiation resistance is still an obstacle in lung cancer treatment.
      Oridonin is a natural compound with promising antitumor efficacy that can trigger
      cancer cell death; however, its direct cellular targets, efficacy as a
      radiosensitizer, and underlying mechanisms of activity remain unclear. Herein, we
      report that oridonin exhibits additive cytotoxic and antitumor activity with
      radiation using the H460 non-small cell lung cancer cell lines. We assessed the
      effect of oridonin by proliferation, clonogenic, reactive oxygen species (ROS)
      production, DNA damage, and apoptosis assays. In vitro, oridonin enhanced the
      radiation-induced inhibition of cell growth and clonogenic survival. Oridonin
      also facilitated radiation-induced ROS production and DNA damage and enhanced
      apoptotic cell death. In vivo, the combination of oridonin and radiation
      effectively inhibited H460 xenograft tumor growth, with higher caspase-3
      activation and H2A histone family member X (H2AX) phosphorylation compared with
      that of radiation alone. Our findings suggest that oridonin possesses a novel
      mechanism to enhance radiation therapeutic responses by increasing DNA damage and
      apoptosis. In conclusion, oridonin may be a novel small molecule to improve
      radiotherapy in non-small cell lung cancer.

PMID- 30104474
TI  - ABE-VIEW: Android Interface for Wireless Data Acquisition and Control.
AB  - Advances in scientific knowledge are increasingly supported by a growing
      community of developers freely sharing new hardware and software tools. In this
      spirit we have developed a free Android app, ABE-VIEW, that provides a flexible
      graphical user interface (GUI) populated entirely from a remote instrument by
      ascii-coded instructions communicated wirelessly over Bluetooth. Options include
      an interactive chart for plotting data in real time, up to 16 data fields, and
      virtual controls including buttons, numerical controls with user-defined range
      and resolution, and radio buttons which the user can use to send coded
      instructions back to the instrument. Data can be recorded into comma delimited
      files interactively at the user's discretion. Our original objective of the
      project was to make data acquisition and control for undergraduate engineering
      labs more modular and affordable, but we have also found that the tool is highly
      useful for rapidly testing novel sensor systems for iterative improvement. Here
      we document the operation of the app and syntax for communicating with it. We
      also illustrate its application in undergraduate engineering labs on dynamic
      systems modeling, as well as for identifying the source of harmonic distortion
      affecting electrochemical impedance measurements at certain frequencies in a
      novel wireless potentiostat.

PMID- 30104477
TI  - The Effect of Spot Size Combination Mode on Ablation Morphology of Aluminum Alloy
      by Millisecond-Nanosecond Combined-Pulse Laser.
AB  - Ablation morphology affects the quality of laser processing. Therefore, the
      control of ablation morphology is very important. The influence of spot size
      combination mode on the ablation morphology of aluminum alloy is studied for the
      first time. Experimental results show that when the nanosecond laser spot is
      larger, the ablation morphology looks like a bowl-shape, and there is little
      solidification near the edge. When the nanosecond laser spot is smaller, the
      shape of the ablation morphology is similar to a hole, and the protuberance is
      formed near the edge of the cavity. Through the analysis and simulation of the
      physical model, the physical mechanism, which describes the influence of the spot
      size combination mode on the molten pool, is discussed. The research results of
      this paper have important guiding significance for the control of laser
      processing effect.

PMID- 30104476
TI  - Tomato ATP-Binding Cassette Transporter SlABCB4 Is Involved in Auxin Transport in
      the Developing Fruit.
AB  - Plant ATP binding cassette (ABC) transporters are membrane proteins that are
      important for transporting a wide range of compounds, including secondary
      metabolites and phytohormones. In Arabidopsis, some members of the ABCB subfamily
      of ABC transporter, also known as Multi-Drug Resistance proteins (MDRs), have
      been implicated in auxin transport. However, reports on the roles of the auxin
      mediated ABCBs in fleshy fruit development are rare. Here, we present that
      SlABCB4, a member of the tomato ABCB subfamily, transports auxin in the
      developing fruit of tomato. Transient expression of SlABCB4-GFP fusion proteins
      in tobacco cells showed plasma membrane localization. The transport activity of
      SlABCB4, expressed in Nicotiana benthamiana protoplasts, revealed substrate
      specificity for indole-3-acetic acid export. Gene expression analysis of SlABCB4
      revealed high expression levels at the early stages of fruit development.
      Therefore, SlABCB4 is considered to facilitate auxin distribution in tomato
      fruit, which is important for tomato fruit development.

PMID- 30104473
TI  - Molecular Targets in Hepatocarcinogenesis and Implications for Therapy.
AB  - Hepatocarcinogenesis comprises of multiple, complex steps that occur after liver
      injury and usually involve several pathways, including telomere dysfunction, cell
      cycle, WNT/beta-catenin signaling, oxidative stress and mitochondria dysfunction,
      autophagy, apoptosis, and AKT/mTOR signaling. Following liver injury, gene
      mutations, accumulation of oxidative stress, and local inflammation lead to cell
      proliferation, differentiation, apoptosis, and necrosis. The persistence of this
      vicious cycle in turn leads to further gene mutation and dysregulation of pro-
      and anti-inflammatory cytokines, such as interleukin (IL)-1beta, IL-6, IL-10, IL
      12, IL-13, IL-18, and transforming growth factor (TGF)-beta, resulting in immune
      escape by means of the NF-kappaB and inflammasome signaling pathways. In this
      review, we summarize studies focusing on the roles of hepatocarcinogenesis and
      the immune system in liver cancer. In addition, we furnish an overview of recent
      basic and clinical studies to provide a strong foundation to develop novel anti
      carcinogenesis targets for further treatment interventions.

PMID- 30104475
TI  - Genome Sequencing and Carbohydrate-Active Enzyme (CAZyme) Repertoire of the White
      Rot Fungus Flammulina elastica.
AB  - Next-generation sequencing (NGS) of the Flammulina elastica (wood-rotting
      basidiomycete) genome was performed to identify carbohydrate-active enzymes
      (CAZymes). The resulting assembly (31 kmer) revealed a total length of 35,045,521
      bp (49.7% GC content). Using the AUGUSTUS tool, 12,536 total gene structures were
      predicted by ab initio gene prediction. An analysis of orthologs revealed that
      6806 groups contained at least one F. elastica protein. Among the 12,536
      predicted genes, F. elastica contained 24 species-specific genes, of which 17
      genes were paralogous. CAZymes are divided into five classes: glycoside
      hydrolases (GHs), carbohydrate esterases (CEs), polysaccharide lyases (PLs),
      glycosyltransferases (GTs), and auxiliary activities (AA). In the present study,
      annotation of the predicted amino acid sequences from F. elastica genes using the
      dbCAN CAZyme database revealed 508 CAZymes, including 82 AAs, 218 GHs, 89 GTs, 18
      PLs, 59 CEs, and 42 carbohydrate binding modules in the F. elastica genome.
      Although the CAZyme repertoire of F. elastica was similar to those of other
      fungal species, the total number of GTs in F. elastica was larger than those of
      other basidiomycetes. This genome information elucidates newly identified wood
      degrading machinery in F. elastica, offers opportunities to better understand
      this fungus, and presents possibilities for more detailed studies on
      lignocellulosic biomass degradation that may lead to future biotechnological and
      industrial applications.

PMID- 30104480
TI  - Delamination Study in Edge Trimming of Basalt Fiber Reinforced Plastics (BFRP).
AB  - Although there are many machining studies of carbon and glass fiber reinforced
      plastics, delamination and tool wear of basalt fiber reinforced plastics (BFRP)
      in edge trimming has not yet studied. This paper presents an end milling study of
      BFRP fabricated by resin transfer molding (RTM), to evaluate delamination types
      at the top layer of the machined edge with different cutting conditions (cutting
      speed, feed rate and depth of cut) and fiber volume fraction (40% and 60%). This
      work quantifies delamination types, using a parameter Sd/L, that evaluates the
      delamination area (Sd) and the length (L), taking into account tool position in
      the yarn and movement of yarns during RTM process, which show the random nature
      of delamination. Delamination was present in all materials with 60% of fiber
      volume. High values of tool wear did not permit to machine the material due to an
      excessive delamination. Type II delamination was the most usual delamination type
      and depth of cut has influence on this type of delamination.

PMID- 30104478
TI  - Sensors for Fetal Hypoxia and Metabolic Acidosis: A Review.
AB  - This article reviews existing clinical practices and sensor research undertaken
      to monitor fetal well-being during labour. Current clinical practices that
      include fetal heart rate monitoring and fetal scalp blood sampling are shown to
      be either inadequate or time-consuming. Monitoring of lactate in blood is
      identified as a potential alternative for intrapartum fetal monitoring due to its
      ability to distinguish between different types of acidosis. A literature review
      from a medical and technical perspective is presented to identify the current
      advancements in the field of lactate sensors for this application. It is
      concluded that a less invasive and a more continuous monitoring device is
      required to fulfill the clinical needs of intrapartum fetal monitoring. Potential
      specifications for such a system are also presented in this paper.

PMID- 30104479
TI  - Therapeutic Aspects of Carbon Monoxide in Cardiovascular Disease.
AB  - Carbon monoxide (CO) is being increasingly recognized as a potential therapeutic
      with important signaling functions in various diseases. Carbon monoxide-releasing
      molecules (CORMs) show anti-apoptotic, anti-inflammatory, and anti-oxidant
      effects on the tissues of organisms, thus contributing to tissue homeostasis. An
      increase in reactive oxygen species production from the mitochondria after
      exposure to CO is also considered one of the underlying mechanisms of
      cardioprotection, although mitochondrial inhibition is the main toxic mechanism
      of CO poisoning. This review highlights the mechanism of the biological effects
      of CO and its potential application as a therapeutic in clinical settings,
      including in cardiovascular diseases. This review also discusses the obstacles
      and limitations of using exogenous CO or CORMs as a therapeutic option, with
      respect to acute CO poisoning.

PMID- 30104483
TI  - Application of Aluminium Flakes in Fabrication of Open-Cell Aluminium Foams by
      Space Holder Method.
AB  - In the current study, a first attempt at using aluminum flakes for the
      manufacture of open-cell aluminum foams with the space holder method is
      presented. The method involves powder mixing, compaction, leaching, and sintering
      processes. Saccharose particles were used as space holders, and multiple
      parameters were investigated to optimize the manufacturing processing route in
      order to produce high-quality open-cell aluminum foams with a simple, economic,
      and environmentally friendly method. The implementation of aluminum flakes leads
      to foams with 80 vol.% porosity, an excellent internal open-cell porous
      structure, low green compaction pressures, and does not require the use of
      binding additives.

PMID- 30104481
TI  - Targeted Therapies in Type II Endometrial Cancers: Too Little, but Not Too Late.
AB  - Type II endometrial carcinomas (ECs) are responsible for most endometrial cancer
      related deaths due to their aggressive nature, late stage detection and high
      tolerance for standard therapies. However, there are no targeted therapies for
      type II ECs, and they are still treated the same way as the clinically indolent
      and easily treatable type I ECs. Therefore, type II ECs are in need of new
      treatment options. More recently, molecular analysis of endometrial cancer
      revealed phosphorylation-dependent oncogenic signalling in the
      phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated
      protein kinase (MAPK) pathways to be most frequently altered in type II ECs.
      Consequently, clinical trials tested pharmacologic kinase inhibitors targeting
      these pathways, although mostly with rather disappointing results. In this
      review, we highlight the most common genetic alterations in type II ECs.
      Additionally, we reason why most clinical trials for ECs using targeted kinase
      inhibitors had unsatisfying results and what should be changed in future clinical
      trial setups. Furthermore, we argue that, besides kinases, phosphatases should no
      longer be ignored in clinical trials, particularly in type II ECs, where the
      tumour suppressive phosphatase protein phosphatase type 2A (PP2A) is frequently
      mutated. Lastly, we discuss the therapeutic potential of targeting PP2A for
      (re)activation, possibly in combination with pharmacologic kinase inhibitors.

PMID- 30104485
TI  - Diet-Related Risk Factors for Incident Hypertension During an 11-Year Follow-Up:
      The Korean Genome Epidemiology Study.
AB  - Using long-term follow-up cohort data from the Korean Genome Epidemiology Study,
      we assessed the dietary risk factors for incident hypertension (HTN). In total,
      6792 subjects (3300 males and 3492 females) aged 40-69 years were included in the
      study. Physician-diagnosed HTN self-reported by the participants was used as the
      outcome. Daily intake of 20 food groups was assessed while using a dish-based
      semi-quantitative food-frequency questionnaire. After controlling for known risk
      factors, the food groups that were most closely associated with HTN were
      identified by forward stepwise selection while using the Cox proportional hazards
      model. The median follow-up period was 11.5 years (interquartile range, 6.0-11.7
      years) and the incidence of HTN was 20 per 1000 person-years. Older age, obesity,
      lower education level, high alcohol intake, and having at least one parent with
      HTN were associated with the risk for HTN. In addition, a high intake of salted
      seafood and a low intake of eggs and meat were independently associated with the
      incidence of HTN after controlling for the known risk factors. Those in the top
      quartile of salted seafood intake had a 28% greater risk for incident HTN than
      those in the bottom quartile. The population-attributable fraction of three
      dietary factors accounted for 29.0% of the incidence of HTN. A high intake of
      salted seafood and a low intake of eggs and meat were associated with a greater
      risk for HTN.

PMID- 30104484
TI  - Stealth and Cationic Nanoliposomes as Drug Delivery Systems to Increase
      Andrographolide BBB Permeability.
AB  - (1) Background: Andrographolide (AG) is a natural compound effective for the
      treatment of inflammation-mediated neurodegenerative disorders. The aim of this
      investigation was the preparation of liposomes to enhance the penetration into
      the brain of AG, by modifying the surface of the liposomes by adding Tween 80
      (LPs-AG) alone or in combination with Didecyldimethylammonium bromide (DDAB)
      (CLPs-AG). (2) Methods: LPs-AG and CLPs-AG were physically and chemically
      characterized. The ability of liposomes to increase the permeability of AG was
      evaluated by artificial membranes (PAMPA) and hCMEC/D3 cells. (3) Results: Based
      on obtained results in terms of size, homogeneity, zeta-potential and EE%. both
      liposomes are suitable for parenteral administration. The systems showed
      excellent stability during a month of storage as suspensions or freeze-dried
      products. Glucose resulted the best cryoprotectant agent. PAMPA and hCMEC/D3
      transport studies revealed that LPs-AG and CLPs-AG increased the permeability of
      AG, about an order of magnitude, compared to free AG without alterations in cell
      viability. The caveolae-mediated endocytosis resulted the main mechanism of up
      take for both formulations. The presence of positive charge increased the
      cellular internalization of nanoparticles. (4) Conclusions: This study shows that
      developed liposomes might be ideal candidates for brain delivery of AG.

PMID- 30104486
TI  - A Combined Approach to Predicting Rest in Dogs Using Accelerometers.
AB  - The ability to objectively measure episodes of rest has clear application for
      assessing health and well-being. Accelerometers afford a sensitive platform for
      doing so and have demonstrated their use in many human-based trials and
      interventions. Current state of the art methods for predicting sleep from
      accelerometer signals are either based on posture or low movement. While both
      have proven to be sensitive in humans, the methods do not directly transfer well
      to dogs, possibly because dogs are commonly alert but physically inactive when
      recumbent. In this paper, we combine a previously validated low-movement
      algorithm developed for humans and a posture-based algorithm developed for dogs.
      The hybrid approach was tested on 12 healthy dogs of varying breeds and sizes in
      their homes. The approach predicted state of rest with a mean accuracy of 0.86
      (SD = 0.08). Furthermore, when a dog was in a resting state, the method was able
      to distinguish between head up and head down posture with a mean accuracy of 0.90
      (SD = 0.08). This approach can be applied in a variety of contexts to assess how
      factors, such as changes in housing conditions or medication, may influence a
      dog's resting patterns.

PMID- 30104487
TI  - Energy and Nutrient Issues in Athletes with Spinal Cord Injury: Are They at Risk
      for Low Energy Availability?
AB  - Low energy availability (LEA) and nutrient intake have been well studied in able
      bodied athletes, but there is a lack of research examining these issues amongst
      athletes with spinal cord injury (SCI). To date, there have been no studies that
      have examined energy availability (EA) amongst this population. Furthermore,
      athletes with SCI may experience unique challenges around nutrition that may
      increase their risk of LEA. This review will evaluate the literature and assess
      whether this population is at risk for LEA. Due to the limited research on this
      topic, sedentary individuals with SCI and para athletes were also included in
      this review. Review of the current literature suggests that athletes with SCI may
      be at an increased risk for LEA. While research examining EA and risk of LEA in
      athletes with SCI is lacking, the number of athletes with SCI continues to
      increase; therefore, further research is warranted to assess nutrient and energy
      needs and their risk to this population.

PMID- 30104488
TI  - Lysine Dendrigraft Nanocontainers. Influence of Topology on Their Size and
      Internal Structure.
AB  - Poly-l-ysine dendrigrafts are promising systems for biomedical applications due
      to their biodegradability, biocompatibility, and similarity to dendrimers. There
      are many papers about the use of dendrigrafts as nanocontainers for drug
      delivery. At the same time, the number of studies about their physical properties
      is limited, and computer simulations of dendrigrafts are almost absent. This
      paper presents the results of a systematic molecular dynamics simulation study of
      third-generation lysine dendrigrafts with different topologies. The size and
      internal structures of the dendrigrafts were calculated. We discovered that the
      size of dendrigrafts of the same molecular weight depends on their topology. The
      shape of all studied dendrigrafts is close to spherical. Density profile of
      dendrigrafts depends on their topology.

PMID- 30104490
TI  - Nutritional Composition Assessment of 3000 Individualized Parenteral Nutrition
      Bags in a Tertiary Referral Hospital: Current Prescribing Patterns.
AB  - Individualized parenteral nutrition is the most specialized type of nutritional
      support in the hospital setting. The composition and prescribing patterns for
      parenteral nutrition have evolved due to new emerging scientific evidence. In the
      last few years, there has been a tendency to increase the nitrogen and lipid
      content and decrease the carbohydrate content. To assess the prescribing pattern
      in a tertiary referral hospital in Spain, the nutritional composition of
      individualized parenteral nutrition was evaluated retrospectively from January to
      December of 2016. A total of 3029 parenteral nutrition units were analysed,
      corresponding to 257 hospitalized adult patients. Medical specialists in General
      Surgery and Haematology were the most common petitioners. The three most
      frequently prescribed parenteral nutrition formulae contained 13.4 (28.8%), 15.7
      (19.54%) and 17.9 (17.79%) g of nitrogen. The quantity of carbohydrates and
      lipids showed a mean non-protein calories-to-nitrogen ratio of approximately 78:1
      and a carbohydrate-to-lipid ratio that was near 50:50 in most cases. These
      results suggest a trend towards the administration of parenteral nutrition with a
      high content of nitrogen and smaller proportion of the non-protein components.

PMID- 30104492
TI  - Ambiguity Resolution for Passive 2-D Source Localization with a Uniform Circular
      Array.
AB  - This paper proposes two novel phase-based algorithms for the passive localization
      of a single source with a uniform circular array (UCA) under the case of
      measuring phase ambiguity based on two phase difference observation models, which
      are defined as the unambiguous-relative phase observation model (UARPOM) and the
      ambiguous-relative phase observation model (ARPOM). First, by analyzing the
      varying regularity of the phase differences between the adjacent array elements
      of a UCA, the corresponding relationship between the phase differences and the
      azimuth and elevation angle of the signal is derived. Based on the two phase
      observation models, two corresponding novel algorithms, namely, the phase
      integral accumulation and the randomized Hough transform (RHT), are addressed to
      resolve the phase ambiguity. Then, by using the unambiguous phase differences,
      the closed-form estimates of the azimuth and elevation angles are determined via
      a least squares (LS) algorithm. Compared with the existing phase-based methods,
      the proposed algorithms improve the estimation accuracy. Furthermore, our
      proposed algorithms are more flexible for the selection of an array radius. Such
      an advantage could be applied more broadly in practice than the previous methods
      of ambiguity resolution. Simulation results are presented to verify the
      effectiveness of the proposed algorithm.

PMID- 30104489
TI  - DnaG Primase-A Target for the Development of Novel Antibacterial Agents.
AB  - The bacterial primase-an essential component in the replisome-is a promising but
      underexploited target for novel antibiotic drugs. Bacterial primases have a
      markedly different structure than the human primase. Inhibition of primase
      activity is expected to selectively halt bacterial DNA replication. Evidence is
      growing that halting DNA replication has a bacteriocidal effect. Therefore,
      inhibitors of DNA primase could provide antibiotic agents. Compounds that inhibit
      bacterial DnaG primase have been developed using different approaches. In this
      paper, we provide an overview of the current literature on DNA primases as novel
      drug targets and the methods used to find their inhibitors. Although few
      inhibitors have been identified, there are still challenges to develop inhibitors
      that can efficiently halt DNA replication and may be applied in a clinical
      setting.

PMID- 30104493
TI  - High Performance Gas Separation Mixed Matrix Membrane Fabricated by Incorporation
      of Functionalized Submicrometer-Sized Metal-Organic Framework.
AB  - Mixed matrix membranes (MMMs) attract great attention due to their outstanding
      gas separation performance. The compatibility between the fillers and the polymer
      matrix is one of the key points for the preparation of high-performance MMMs. In
      this work, MMMs consisting of metal-organic frameworks (MOFs) of amine-modified
      Cu-BTC (NH2-Cu-BTC; BTC = 1,3,5-benzenetricarboxylic acid) and submicrometer
      sized amine-modified Cu-BTC (sub-NH2-Cu-BTC) incorporated into a Pebax-1657
      polymer were fabricated for the gas separation. The SEM image and Fourier
      transform infrared spectroscopy (FTIR) spectra showed an increase in the surface
      roughness of MOFs and the presence of amino groups on the surface of Cu-BTC after
      the amination modification, and a decrease in the size of MOFs crystals after the
      submicrometer-sized aminated modification. Gas adsorption analysis indicated that
      NH2-Cu-BTC and sub-NH2-Cu-BTC had a higher gas adsorption capacity for CO2
      compared to the unmodified Cu-BTC. The scanning electron microscopy (SEM) image
      showed that NH2-Cu-BTC and sub-NH2-Cu-BTC, especially sub-NH2-Cu-BTC, had a
      better compatibility with a polyether-block-amide (Pebax) matrix in the MMMs. The
      gas separation performance indicated that the Pebax/sub-NH2-Cu-BTC MMMs evidently
      improved the CO2/N2 and CO2/CH4 selectivity at the expense of a slight CO2
      permeability. The results reveal that modified MOF-filled MMMs possess great
      potential for applications in the CO2 separation field.

PMID- 30104491
TI  - Dietary Approaches for Japanese Patients with Diabetes: A Systematic Review.
AB  - This study aimed to elucidate the effect of an energy restricted and carbohydrate
      restricted diet on the management of Japanese diabetes patients. Several
      databases including MEDLINE, EMBASE, and the Japan Medical Abstracts Society were
      searched for relevant articles published prior to June 2017. The articles
      identified were systematically reviewed. We identified 286 articles on an energy
      restricted diet, assessed seven and included two studies in our review. On a
      carbohydrate restricted diet, 75 articles were extracted, seven articles assessed
      and three included in the review, of which two were the studies that were
      selected for the energy restricted diet group, since they compared energy
      restricted diets with carbohydrate restricted diets. All selected studies were on
      Japanese patients with type 2 diabetes. No studies for type 1 diabetes were found
      in our search. Two randomized controlled trials on an energy restricted diet were
      also included in the three studies for a carbohydrate restricted diet. All the
      three randomized controlled trials showed better glucose management with the
      carbohydrate restricted diet. Our study revealed that there is very little
      evidence on diets, particularly in Japanese patients with diabetes, and that the
      energy restricted diet, which has been recommended by the Japan Diabetes Society
      in the sole dietary management approach, is not supported by any scientific
      evidence. Our findings suggest that the carbohydrate restricted diet, but not the
      energy restricted diet, might have short term benefits for the management of
      diabetes in Japanese patients. However, since our analysis was based on a limited
      number of small randomized controlled trials, large scale and/or long term trials
      examining the dietary approaches in these patients are needed to confirm our
      findings.

PMID- 30104495
TI  - Aging Response and Precipitation Behavior after 5% Pre-Deformation of an Al-Mg-Si
      Cu Alloy.
AB  - In this study, Al-1.00 Mg-0.65 Si-0.24 Cu alloy was solution heat-treated, water
      quenched, and then pre-deformed for 5% before aging. The peak hardness and yield
      strength of the pre-deformed sample with subsequent artificial aging were similar
      to that of a T6 condition sample. It was also found that the pre-deformation
      treatment could inhibit the negative influence of natural aging to some degree.
      After seven days of natural aging, the pre-deformed sample obtained better peak
      hardness and yield strength upon artificial aging than the sample without pre
      deformation. In addition, the pre-deformation treatment could reduce 50% of the
      artificial aging time to reach the peak aging condition compared with T6
      treatment. For the peak aged condition in the pre-deformed sample, transmission
      electron microscopy (TEM) observation found two types of precipitates exhibited
      along the dislocations besides the beta" precipitates in the Al matrix. Both
      precipitates had disordered atomic arrangements on the ordered subcell (Si
      network). The disordered precipitates occupied a number of Mg and Si atoms,
      resulting in less beta" precipitates formed during artificial aging at 180 
      degrees C.

PMID- 30104494
TI  - Vegetable Diversity, Injurious Falls, and Fracture Risk in Older Women: A
      Prospective Cohort Study.
AB  - The importance of vegetable diversity for the risk of falling and fractures is
      unclear. Our objective was to examine the relationship between vegetable
      diversity with injurious falling and fractures leading to hospitalization in a
      prospective cohort of older Australian women (n = 1429, >=70 years). Vegetable
      diversity was quantified by assessing the number of different vegetables consumed
      daily. Vegetable intake (75 g servings/day) was estimated using a validated food
      frequency questionnaire at baseline (1998). Over 14.5 years, injurious falls
      (events = 568, 39.7%), and fractures (events = 404, 28.3%) were captured using
      linked health records. In multivariable-adjusted Cox regression models, women
      with greater vegetable diversity (per increase in one different vegetable/day)
      had lower relative hazards for falls (8%; p = 0.02) and fractures (9%; p = 0.03).
      A significant interaction between daily vegetable diversity (number/day) and
      total vegetable intake (75 g servings/day) was observed for falls (pinteraction =
      0.03) and fractures (pinteraction < 0.001). The largest benefit of higher
      vegetable diversity were observed in the one third of women with the lowest
      vegetable intake (<2.2 servings/day; falls HR 0.83 95% CI (0.71-0.98); fractures
      HR 0.74 95% CI (0.62-0.89)). Increasing vegetable diversity especially in older
      women with low vegetable intake may be an effective way to reduce injurious fall
      and fracture risk.

PMID- 30104482
TI  - Early Events in Japanese Encephalitis Virus Infection: Viral Entry.
AB  - Japanese encephalitis virus (JEV), a mosquito-borne zoonotic flavivirus, is an
      enveloped positive-strand RNA virus that can cause a spectrum of clinical
      manifestations, ranging from mild febrile illness to severe neuroinvasive
      disease. Today, several killed and live vaccines are available in different parts
      of the globe for use in humans to prevent JEV-induced diseases, yet no antivirals
      are available to treat JEV-associated diseases. Despite the progress made in
      vaccine research and development, JEV is still a major public health problem in
      southern, eastern, and southeastern Asia, as well as northern Oceania, with the
      potential to become an emerging global pathogen. In viral replication, the entry
      of JEV into the cell is the first step in a cascade of complex interactions
      between the virus and target cells that is required for the initiation,
      dissemination, and maintenance of infection. Because this step determines
      cell/tissue tropism and pathogenesis, it is a promising target for antiviral
      therapy. JEV entry is mediated by the viral glycoprotein E, which binds virions
      to the cell surface (attachment), delivers them to endosomes (endocytosis), and
      catalyzes the fusion between the viral and endosomal membranes (membrane fusion),
      followed by the release of the viral genome into the cytoplasm (uncoating). In
      this multistep process, a collection of host factors are involved. In this
      review, we summarize the current knowledge on the viral and cellular components
      involved in JEV entry into host cells, with an emphasis on the initial virus-host
      cell interactions on the cell surface.

PMID- 30104496
TI  - Contact-Lens Biosensors.
AB  - Rapid diagnosis and screening of diseases have become increasingly important in
      predictive and preventive medicine as they improve patient treatment strategies
      and reduce cost as well as burden on our healthcare system. In this regard,
      wearable devices are emerging as effective and reliable point-of-care diagnostics
      that can allow users to monitor their health at home. These wrist-worn, head
      mounted, smart-textile, or smart-patches devices can offer valuable information
      on the conditions of patients as a non-invasive form of monitoring. However, they
      are significantly limited in monitoring physiological signals and biomechanics,
      and, mostly, rely on the physical attributes. Recently, developed wearable
      devices utilize body fluids, such as sweat, saliva, or skin interstitial fluid,
      and electrochemical interactions to allow continuous physiological condition and
      disease monitoring for users. Among them, tear fluid has been widely utilized in
      the investigation of ocular diseases, diabetes, and even cancers, because of its
      easy accessibility, lower complexity, and minimal invasiveness. By determining
      the concentration change of analytes within the tear fluid, it would be possible
      to identify disease progression and allow patient-oriented therapies. Considering
      the emerging trend of tear-based biosensing technology, this review article aims
      to focus on an overview of the tear fluid as a detection medium for certain
      diseases, such as ocular disorders, diabetes, and cancer. In addition, the rise
      and application of minimally invasive detection and monitoring via integrated
      contact lens biosensors will also be addressed, in regards to their practicality
      and current developmental progress.

PMID- 30104498
TI  - JASPAC: Japan Spastic Paraplegia Research Consortium.
AB  - Hereditary spastic paraplegias (HSPs) are a group of neurodegenerative disorders
      characterized by weakness and spasticity of the lower extremities. HSPs are
      heterogeneous disorders that involve over 80 causative genes. The frequency of
      HSPs is estimated to be 10-100/1,000,000. With this background, the Japanese
      research group "Japan Spastic Paraplegia Research Consortium: JASPAC" was
      organized in 2006 to elucidate the molecular epidemiologies of HSPs in Japan and
      the molecular pathologies of HSPs. To date, the JASPAC has collected 714 HSP
      families and analyzed 488 index patients. We found 279 pathogenic variants or
      probable pathogenic variants of causative genes in the 488 HSP patients.
      According to our results, we found 178 families with autosomal dominant patients
      (65%), and 101 with autosomal recessive and sporadic patients (48%). We found 119
      patients with SPG4, 17 with SPG3A, 15 with SPG31, 13 with SPG11, and 11 with
      SPG10. Other HSP genes were the cause in less than five patients. On the other
      hand, we could not find causative genes in 35% of the autosomal dominant
      patients, or 52% of the autosomal recessive and sporadic patients. We are now
      trying to find new causative genes and elucidate the molecular mechanisms
      underlying HSPs.

PMID- 30104499
TI  - Green Communication for Tracking Heart Rate with Smartbands.
AB  - The trend of using wearables for healthcare is steeply increasing nowadays, and,
      consequently, in the market, there are several gadgets that measure several body
      features. In addition, the mixed use between smartphones and wearables has
      motivated research like the current one. The main goal of this work is to reduce
      the amount of times that a certain smartband (SB) measures the heart rate (HR) in
      order to save energy in communications without significantly reducing the utility
      of the application. This work has used an SB Sony 2 for measuring heart rate, Fit
      API for storing data and Android for managing data. The current approach has been
      assessed with data from HR sensors collected for more than three months. Once all
      HR measures were collected, then the current approach detected hourly ranges
      whose heart rate were higher than normal. The hourly ranges allowed for
      estimating the time periods of weeks that the user could be at potential risk for
      measuring frequently in these (60 times per hour) ranges. Out of these ranges,
      the measurement frequency was lower (six times per hour). If SB measures an
      unusual heart rate, the app warns the user so they are aware of the risk and can
      act accordingly. We analyzed two cases and we conclude that energy consumption
      was reduced in 83.57% in communications when using training of several weeks. In
      addition, a prediction per day was made using data of 20 users. On average, tests
      obtained 63.04% of accuracy in this experimentation using the training over the
      data of one day for each user.

PMID- 30104500
TI  - Using Calcination Remediation to Stabilize Heavy Metals and Simultaneously Remove
      Polycyclic Aromatic Hydrocarbons in Soil.
AB  - Co-contaminated soils containing heavy metals and polycyclic aromatic
      hydrocarbons (PAHs) are an environmental and human health risk. Research into the
      remediation of these soils is imperative. In this paper, a novel investigation
      utilizing calcination technique to stabilize heavy metals and simultaneously
      remove PAHs in soil was conducted. Calcination temperature (300-700  degrees C)
      was observed to play a dominant role in heavy metal stabilization and PAH removal
      in soils. However, calcination time (0.5-8 h) had no significant effect on these
      contaminants during calcination at different temperatures. Considering the
      remediation cycle requirements and economic costs of engineering, we suggested
      that the optimal calcination condition for Zn, Cu, naphthalene, and fluoranthene
      was at 700  degrees C for 0.5 h, and the corresponding stabilization or removal
      efficiency values were 96.95%, 98.41%, 98.49%, and 98.04%, respectively. Results
      indicate that calcination as a remedial strategy exhibits a bright future for
      practical applications in the simultaneous stabilization of heavy metals and PAH
      removal from co-contaminated sites.

PMID- 30104497
TI  - New Development of Biomarkers for Gastrointestinal Cancers: From Neoplastic Cells
      to Tumor Microenvironment.
AB  - Biomarkers refer to a plethora of biological characteristics that can be
      quantified to facilitate cancer diagnosis, forecast the prognosis of disease, and
      predict a response to treatment. The identification of objective biomarkers is
      among the most crucial steps in the realization of individualized cancer care.
      Several tumor biomarkers for gastrointestinal malignancies have been applied in
      the clinical setting to help differentiate between cancer and other conditions,
      facilitate patient selection for targeted therapies, and to monitor treatment
      response and recurrence. With the coming of the immunotherapy age, the need for a
      new development of biomarkers that are indicative of the immune response to
      tumors are unprecedentedly urgent. Biomarkers from the tumor microenvironment,
      tumor genome, and signatures from liquid biopsies have been explored, but the
      majority have shown a limited prognostic or predictive value as single
      biomarkers. Nevertheless, use of multiplex biomarkers has the potential to
      provide a significantly increased diagnostic accuracy compared to traditional
      single biomarker. A comprehensive analysis of immune-biomarkers is needed to
      reveal the dynamic and multifaceted anti-tumor immunity and thus imply for the
      rational design of assays and combinational strategies.

PMID- 30104503
TI  - Aggregation Site Choice by Gregarious Nymphs of the Desert Locust, Schistocerca
      gregaria, in the Sahara Desert of Mauritania.
AB  - Animals often aggregate at certain sites during vulnerable periods such as night
      roosting as an anti-predatory strategy. Some migratory gregarious animals must
      regularly find new night-roosting sites, but how they synchronously choose such
      sites is poorly understood. We examined how gregarious nymphs of the desert
      locust, Schistocerca gregaria Forskal (Orthoptera: Acrididae), aggregate at
      certain plants for night-roosting in the Sahara Desert. Migratory bands of last
      instar nymphs climbed trees around dusk and roosted there overnight. A spatial
      autocorrelation analysis of plants indicated that the larger locust groups formed
      at the larger plants within the local plant community. Other large groups were
      not formed near the large tree, but smaller groups were patchily distributed.
      Plant height was the primary cue used by migratory bands to choose night-roosting
      plants. A nearest-neighbor distance analysis showed that single conspicuous large
      trees with scattered smaller plants were distributed locally. This plant
      community structure and negative geotactic ascending behavior of gregarious
      nymphs may force them to concentrate at the landmark plant from all directions
      and afar. This plant-size-dependent roosting site choice may contribute for
      developing artificial trapping systems for locusts and inciting to a new
      environment-friendly night control approach.

PMID- 30104501
TI  - Increased Adult Aedes aegypti and Culex quinquefasciatus (Diptera: Culicidae)
      Abundance in a Dengue Transmission Hotspot, Compared to a Coldspot, within
      Kaohsiung City, Taiwan.
AB  - The assumption that vector abundance differences might drive spatial and temporal
      heterogeneities in vector-borne disease transmission is common, though data
      supporting it is scarce. Here, we present data from two common mosquito species
      Aedes aegypti (Linnaeus) and Culex quinquefasciatus Say, biweekly sampled as
      adults, from March 2016 through December 2017, with BG-sentinel traps in two
      neighboring districts of Kaohsiung City (KC), Taiwan. One district has
      historically been a dengue transmission hotspot (Sanmin), and the other a
      coldspot (Nanzih). We collected a total 41,027 mosquitoes, and we found that
      average mosquito abundance (mean +/- S.D.) was higher in Sanmin (Ae. aegypti:
      9.03 +/- 1.46; Cx. quinquefasciatus: 142.57 +/- 14.38) than Nanzih (Ae. aegypti:
      6.21 +/- 0.47; Cx. quinquefasciatus: 63.37 +/- 8.71) during the study period. In
      both districts, Ae. aegypti and Cx. quinquefasciatus population dynamics were
      sensitive to changes in temperature, the most platykurtic environmental variable
      at KC during the study period, a pattern predicted by Schmalhausen's law, which
      states that organisms are more sensitive to small changes in environmental
      variables whose average value is more uncertain than its extremes. Our results
      also suggest that differences in Ae. aegypti abundance might be responsible for
      spatial differences in dengue transmission at KC. Our comparative approach, where
      we also observed a significant increment in the abundance of Cx. quinquefasciatus
      in the dengue transmission hotspot, suggests this area might be more likely to
      experience outbreaks of other vector borne diseases and should become a primary
      focus for vector surveillance and control.

PMID- 30104502
TI  - Using the Mutation-Selection Framework to Characterize Selection on Protein
      Sequences.
AB  - When mutational pressure is weak, the generative process of protein evolution
      involves explicit probabilities of mutations of different types coupled to their
      conditional probabilities of fixation dependent on selection. Establishing this
      mechanistic modeling framework for the detection of selection has been a goal in
      the field of molecular evolution. Building on a mathematical framework proposed
      more than a decade ago, numerous methods have been introduced in an attempt to
      detect and measure selection on protein sequences. In this review, we discuss the
      structure of the original model, subsequent advances, and the series of
      assumptions that these models operate under.

PMID- 30104504
TI  - Software Architecture and Framework to Develop NFC-Based Applications.
AB  - Applications are employing Near Field Communication (NFC) technology to interact
      with physical objects by using NFC tags. The architecture to implement these
      kinds of applications varies according to non-functional requirements such as the
      physical environment where the application is running, the flexibility to adapt
      the information to be manipulated through physical objects, etc. To cope with
      these challenges, this paper proposes a Model-driven Architecture (MDA) where
      designers are able to model the configuration of the system according to NFC
      based system requirements. Through a model-to-text transformation process, the
      MDA also provides developers with templates of source code for the applications
      that support the system. The proposed MDA process defines a Platform Independent
      Model (PIM) which supports a Domain Specific Language (DSL) implemented as an
      Eclipse platform plugin that provides designers with a graphical model editor,
      and a model to text transformation, to generate the source code templates using
      the Acceleo transformation language. The paper also presents the Albacete Photo
      Gallery case of study to illustrate the modelling process. The main benefit of
      the proposal is that it allows developers to create mixed environments where the
      availability and flexibility of NFC based interaction systems can be easily
      configured, extended and maintained.

PMID- 30104505
TI  - Risperidone Controlled Release Microspheres Based on Poly(Lactic Acid)
      Poly(Propylene Adipate) Novel Polymer Blends Appropriate for Long Acting
      Injectable Formulations.
AB  - The present study evaluates the preparation of risperidone controlled release
      microspheres as appropriate long-acting injectable formulations based on a series
      of novel biodegradable and biocompatible poly(lactic acid)-poly(propylene
      adipate) (PLA/PPAd) polymer blends. Initially, PPAd was synthesized using a two
      stage melt polycondensation method (esterification and polycondensation) and
      characterized by 1H-NMR, differential scanning calorimetry (DSC), and powder X
      ray diffraction (XRD) analyses. DSC and XRD results for PLA/PPAd blends (prepared
      by the solvent evaporation method) showed that these are immiscible, while
      enzymatic hydrolysis studies performed at 37  degrees C showed increased mass
      loss for PPAd compared to PLA. Risperidone-polyester microparticles prepared by
      the oil-water emulsification/solvent evaporation method showed smooth spherical
      surface with particle sizes from 1 to 15 MUm. DSC, XRD, and Fourier-transformed
      infrared (FTIR) analyses showed that the active pharmaceutical ingredient (API)
      was dispersed in the amorphous phase within the polymer matrices, whereas in
      vitro drug release studies showed risperidone controlled release rates in all
      PLA/PPAd blend formulations. Finally, statistical moment analysis showed that
      polyester hydrolysis had a major impact on API release kinetics, while in
      PLA/PPAd blends with high PLA content, drug release was mainly controlled by
      diffusion.

PMID- 30104507
TI  - Real-Time Monitoring of Bond Slip between GFRP Bar and Concrete Structure Using
      Piezoceramic Transducer-Enabled Active Sensing.
AB  - Glass fiber-reinforced polymers (GFRPs) have received increasing attention in
      recent years due to their overall performance of light weight, low cost and
      corrosion resistance, and they are increasingly used as reinforcement in concrete
      structures. However, GFRP material has low elastic modulus and linear elastic
      properties compared with steel bars, which introduces different bonding
      characteristics between bars and concrete. Therefore, a reliable monitoring
      method is urgently needed to detect the bond slip in GFRP-reinforced concrete
      structures. In this paper, a piezoceramic-based active sensing approach is
      proposed and developed to find the debonding between a GFRP bar and the concrete
      structure. In the proposed method, we utilize PZT (lead zirconate titanate) as
      two transducers. One acts as an actuator which is buried in the concrete
      structure, and the other acts as a sensor which is attached to the GFRP bar by
      taking advantage of machinability of the GRRP material. Both transducers are
      strategically placed to face each other across from the interface between the
      GFRP bar and the concrete. The actuator provokes a stress wave that travels
      through the interface. Meanwhile, the PZT patch that is attached to the GFRP bar
      is used to detect the propagating stress wave. The bonding condition determines
      how difficult it is for the stress wave traveling through the interface. The
      occurrence of a bond slip leads to cracks between the bar and the concrete, which
      dramatically reduces the energy carried by the stress wave through the interface.
      In this research, two specimens equipped with the PZT transducers are fabricated,
      and pull-out tests are conducted. To analyze the active sensing data, we use
      wavelet packet analysis to compute the energy transferred to the sensing PZT
      patch throughout the process of debonding. Experimental results illustrate that
      the proposed method can accurately capture the bond slip between the GFRP bar and
      the concrete.

PMID- 30104508
TI  - Ursolic Acid-Induced Apoptosis via Regulation of the PI3K/Akt and MAPK Signaling
      Pathways in Huh-7 Cells.
AB  - Ursolic acid (UA), is a kind of triterpene acid that exhibits wide biological
      properties. In this article, the effects of UA on apoptosis and the proliferation
      of human hepatoma Huh-7 cells were reported. The MTT results showed that cell
      viability of Huh-7 was reduced in a concentration and time-dependent effect. In
      addition, DAPI staining was used to detected condensation of chromatin in
      nucleus. Apoptotic cell population was examined using Annexin V/PI staining. The
      results showed that exposure to UA affected extrinsic and intrinsic pathways
      through, reduced expression of Bcl-2, Mcl-1, and TCTP; increased levels of the
      apoptotic proteins TNF-alpha, Fas, FADD, and Bax; and activation of cleaved
      caspase-3 and PARP. UA also inhibited the p-Akt and p38 MAPK signaling
      transduction pathways, and increased activity in the p-ERK signaling pathway.
      Taken together, UA inhibited the cell growth of Huh-7 cells and affected
      apoptosis, via regulated cellular signaling transduction.

PMID- 30104509
TI  - Association between Oral Health-Related Quality of Life in People with Rare
      Diseases and Their Satisfaction with Dental Care in the Health System of the
      Federal Republic of Germany.
AB  - BACKGROUND: The aim of this study was to examine the current dental care
      situation in Germany from the perspective of those affected by a rare disease,
      especially concerning their satisfaction with the German dental health care
      system, and thus assess the relationship between their perspective and their oral
      health-related quality of life (OHRQoL). METHODS: A questionnaire regarding their
      experiences with the dental assistance and the health care system, such as the
      OHIP-14, was sent to the member associations of the organization of self-help
      groups for rare diseases ACHSE e.V. The correlation between OHIP-14 values and
      patient's perspective was statistically analyzed by the non-parametric Tau de
      Kendall test (p < 0.05). RESULTS: There was a statistically significant
      correlation between the OHIP score and the patient's perspective regarding dental
      assistance and health care system (p < 0.05). For those surveyed who were
      satisfied with the support of the health care system, an average OHIP score of
      8.54 +/- 10.45 points (range: 0-48) was determined. The group that did not feel
      sufficiently supported by the health care system had an average OHIP score of
      16.07 +/- 13.43 points (range: 0-56). DISCUSSION: The majority of respondents
      with rare diseases are dissatisfied with the German health care system and its
      support with regard to dental care.

PMID- 30104510
TI  - Synthesis and Preliminary Evaluation of Biological Activity of Glycoconjugates
      Analogues of Acyclic Uridine Derivatives.
AB  - Herein we present the methodology for obtaining glycosyltransferase inhibitors,
      analogues of natural enzyme substrates of donor-type: UDP-glucose and UDP
      galactose. The synthesis concerned glycoconjugates, nucleoside analogues
      containing an acyclic ribose mimetic linked to a uracil moiety in their
      structure. The biological activity of the synthesised compounds was determined on
      the basis of their ability to inhibit the model enzyme action of beta-1,4
      galactosyltransferase from bovine milk. The obtained results allowed to expand
      and supplement the existing library of synthetic compounds that are able to
      regulate the biological activity of enzymes from the GT class.

PMID- 30104511
TI  - Measurement of Unmanned Aerial Vehicle Attitude Angles Based on a Single Captured
      Image.
AB  - The limited load capacity and power resources of small-scale fixed-wing drones
      mean that it is difficult to employ internal high-precision inertial navigation
      devices to assist with the landing procedure. As an alternative, this paper
      proposes an attitude measurement system based on a monocular camera. The attitude
      angles are obtained from a single captured image containing five coded landmark
      points using the radial constraint method and three-dimensional coordinate
      transformations. The landing procedure is simulated for pitch angles from -15 ?
      to -40 ? , roll angles from -15 ? to +15 ? and yaw angles from -15 ? to +15 ? .
      For roll and pitch angles of approximately 0 ? and -25 ? , respectively, the
      accuracy of the method reaches 0.01 ? and 0.04 ? . This UAV attitude measurement
      system obtains an attitude angle by a single captured image, which has great
      potential for assisting with the landing of small-scale fixed-wing UAVs.

PMID- 30104513
TI  - A Non-Contact Measuring System for In-Situ Surface Characterization Based on
      Laser Confocal Microscopy.
AB  - The characterization of surface topographic features on a component is typically
      quantified using two-dimensional roughness descriptors which are captured by off
      line desktop instruments. Ideally any measurement system should be integrated
      into the manufacturing process to provide in-situ measurement and real-time
      feedback. A non-contact in-situ surface topography measuring system is proposed
      in this paper. The proposed system utilizes a laser confocal sensor in both
      lateral and vertical scanning modes to measure the height of the target features.
      The roughness parameters are calculated in the developed data processing software
      according to ISO 4287. To reduce the inherent disadvantage of confocal
      microscopy, e.g., scattering noise at steep angles and background noise from
      specular reflection from the optical elements, the developed system has been
      calibrated and a linear correction factor has been applied in this study. A
      particular challenge identified for this work is the in-situ measurement of
      features generated by a robotized surface finishing system. The proposed system
      was integrated onto a robotic arm with the measuring distance and angle adjusted
      during measurement based on a CAD model of the component in question.
      Experimental data confirms the capability of this system to measure the surface
      roughness within the Ra range of 0.2-7 MUm (bandwidth lambdac/lambdas of 300),
      with a relative accuracy of 5%.

PMID- 30104512
TI  - Evaluation of Chlorophyll-a Estimation Approaches Using Iterative Stepwise
      Elimination Partial Least Squares (ISE-PLS) Regression and Several Traditional
      Algorithms from Field Hyperspectral Measurements in the Seto Inland Sea, Japan.
AB  - Harmful algal blooms (HABs) occur frequently in the Seto Inland Sea, bringing
      significant economic and environmental losses for the area, which is well known
      as one of the world's most productive fisheries. Our objective was to develop a
      quantitative model using in situ hyperspectral measurements in the Seto Inland
      Sea to estimate chlorophyll a (Chl-a) concentration, which is a significant
      parameter for detecting HABs. We obtained spectra and Chl-a data at six stations
      from 12 ship-based surveys between December 2015 and September 2017. In this
      study, we used an iterative stepwise elimination partial least squares (ISE-PLS)
      regression method along with several empirical and semi-analytical methods such
      as ocean chlorophyll, three-band model, and two-band model algorithms to retrieve
      Chl-a. Our results showed that ISE-PLS using both the water-leaving reflectance
      (RL) and the first derivative reflectance (FDR) had a better predictive ability
      with higher coefficient of determination (R2), lower root mean squared error
      (RMSE), and higher residual predictive deviation (RPD) values (R2 = 0.77, RMSE =
      1.47 and RPD = 2.1 for RL; R2 = 0.78, RMSE = 1.45 and RPD = 2.13 for FDR).
      However, in this study the ocean chlorophyll (OC) algorithms had poor predictive
      ability and the three-band and two-band model algorithms did not perform well in
      areas with lower Chl-a concentrations. These results support ISE-PLS as a
      potential coastal water quality assessment method using hyperspectral
      measurements.

PMID- 30104506
TI  - Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative
      Disorders.
AB  - Males and females sometimes significantly differ in their propensity to develop
      neurological disorders. Females suffer more from mood disorders such as
      depression and anxiety, whereas males are more susceptible to deficits in the
      dopamine system including Parkinson's disease (PD), attention-deficit
      hyperactivity disorder (ADHD) and autism. Despite this, biological sex is rarely
      considered when making treatment decisions in neurological disorders. A better
      understanding of the molecular mechanism(s) underlying sex differences in the
      healthy and diseased brain will help to devise diagnostic and therapeutic
      strategies optimal for each sex. Thus, the aim of this review is to discuss the
      available evidence on sex differences in neuropsychiatric and neurodegenerative
      disorders regarding prevalence, progression, symptoms and response to therapy. We
      also discuss the sex-related factors such as gonadal sex hormones and sex
      chromosome genes and how these might help to explain some of the clinically
      observed sex differences in these disorders. In particular, we highlight the
      emerging role of the Y-chromosome gene, SRY, in the male brain and its potential
      role as a male-specific risk factor for disorders such as PD, autism, and ADHD in
      many individuals.

PMID- 30104514
TI  - Odor Discrimination by Similarity Measures of Abstract Odor Factor Maps from
      Electronic Noses.
AB  - The aim of this study is to improve the discrimination performance of electronic
      noses by introducing a new method for measuring the similarity of the signals
      obtained from the electronic nose. We constructed abstract odor factor maps
      (AOFMs) as the characteristic maps of odor samples by decomposition of three-way
      signal data array of an electronic nose. A similarity measure for two-way data
      was introduced to evaluate the similarities and differences of AOFMs from
      different samples. The method was assessed by three types of pipe and powder
      tobacco samples. Comparisons were made with other techniques based on PCA, SIMCA,
      PARAFAC and PARAFAC2. The results showed that our method had significant
      advantages in discriminating odor samples with similar flavors or with high VOCs
      release.

PMID- 30104516
TI  - Privacy-Preserving Data Aggregation against False Data Injection Attacks in Fog
      Computing.
AB  - As an extension of cloud computing, fog computing has received more attention in
      recent years. It can solve problems such as high latency, lack of support for
      mobility and location awareness in cloud computing. In the Internet of Things
      (IoT), a series of IoT devices can be connected to the fog nodes that assist a
      cloud service center to store and process a part of data in advance. Not only can
      it reduce the pressure of processing data, but also improve the real-time and
      service quality. However, data processing at fog nodes suffers from many
      challenging issues, such as false data injection attacks, data modification
      attacks, and IoT devices' privacy violation. In this paper, based on the Paillier
      homomorphic encryption scheme, we use blinding factors to design a privacy
      preserving data aggregation scheme in fog computing. No matter whether the fog
      node and the cloud control center are honest or not, the proposed scheme ensures
      that the injection data is from legal IoT devices and is not modified and leaked.
      The proposed scheme also has fault tolerance, which means that the collection of
      data from other devices will not be affected even if certain fog devices fail to
      work. In addition, security analysis and performance evaluation indicate the
      proposed scheme is secure and efficient.

PMID- 30104515
TI  - Organic Bioelectronics: Materials and Biocompatibility.
AB  - Organic electronic materials have been considered for a wide-range of
      technological applications. More recently these organic (semi)conductors
      (encompassing both conducting and semi-conducting organic electronic materials)
      have received increasing attention as materials for bioelectronic applications.
      Biological tissues typically comprise soft, elastic, carbon-based macromolecules
      and polymers, and communication in these biological systems is usually mediated
      via mixed electronic and ionic conduction. In contrast to hard inorganic
      semiconductors, whose primary charge carriers are electrons and holes, organic
      (semi)conductors uniquely match the mechanical and conduction properties of
      biotic tissue. Here, we review the biocompatibility of organic electronic
      materials and their implementation in bioelectronic applications.

PMID- 30104519
TI  - Composition Optimization and Mechanical Properties of Mg-Al-Sn-Mn Alloys by
      Orthogonal Design.
AB  - Nine kinds of rare-earth free Mg-Al-Sn-Mn magnesium alloys were designed by
      orthogonal method. Scanning electron microscopy (SEM), energy dispersive
      spectrometry (EDS), X-ray diffraction (XRD), electron backscatter diffraction
      (EBSD), and tension tests were carried out to investigate the microstructures and
      mechanical properties. As-cast Mg-Al-Sn-Mn alloys have an obvious dendritic
      structure that is composed of alpha-Mg, Mg17Al12, and Mg2Sn phases. After hot
      extrusion, the cast dendrite structure changed into a recrystallized equiaxed
      grain. Mg17Al12 dissolved completely into a matrix, and only alpha-Mg, Mg2Sn, and
      a few Al-Mn phases could be observed. The influence of three alloy elements (Al,
      Sn, and Mn) on grain size, texture intensity, ultimate tensile strength (UTS),
      tensile yield strength (TYS), and elongation (EL) were studied by extreme
      difference analysis method. The content of Mn had the greatest influence on grain
      size. The AT61-0.2Mn and AT73-0.2Mn alloys had the smallest grain, reaching 6.8
      MUm. The content of Al had the greatest influence on the strength; therefore, the
      AT73-0.2Mn alloy had the highest UTS, 322 MPa, and TYS, 202 MPa. The content of
      Sn had the greatest influence on elongation. The AT52-0.4Mn alloy had the highest
      elongation in theory, but it was not included in the nine designed kinds of
      alloys yet. AT52-0.2Mn alloy had the highest elongation in the nine alloys
      (28.4%).

PMID- 30104518
TI  - Orthopedic Professionals' Recognition and Knowledge of Pain and Perceived
      Barriers to Optimal Pain Management at Five Hospitals.
AB  - Pain is a challenge for orthopedic healthcare professionals (OHCP). However, pain
      studies examined the competencies of a single OHCP category, did not consider
      various pain management domains or barriers to optimal pain service, and are
      deficient across the Arabic Eastern Mediterranean region. We surveyed OHCP's
      recognition and knowledge of pain and perceived barriers to optimal pain service
      (361 OHCP, five hospitals). Chi square compared doctors' (n = 63) vs.
      nurses/physiotherapists' (n = 187) views. In terms of pain recognition, more
      nurses had pain management training, confidently assessed pediatric/elderly pain,
      were aware of their departments' pain protocols, and felt that their patients
      receive proper pain management. More doctors comfortably prescribed opiate
      medications and agreed that some nationalities were more sensitive to pain. For
      pain knowledge, more nurses felt patients are accurate in assessing their pain,
      vital signs are accurate in assessing children's pain, children feel less pain
      because of nervous system immaturity, narcotics are not preferred due respiratory
      depression, and knew pre-emptive analgesia. As for barriers to optimal pain
      service, less nurses agreed about the lack of local policies/guidelines,
      knowledge, and skills; time to pre-medicate patients; knowledge about
      medications; complexity of the clinical environment; and physicians being not
      comfortable prescribing pain medication. We conclude that doctors required
      confidence in pain, especially pediatric and geriatric pain, using vital signs in
      assessing pain and narcotics use. Their most perceived barriers were lack of
      local policies/guidelines and skills. Nurses required more confidence in
      medications, caring for patients on narcotics, expressed fewer barriers than
      doctors, and the complexity of the clinical environment was their highest
      barrier. Educational programs with clinical application could improve OHCPs' pain
      competencies/clinical practices in pain assessment and administration of
      analgesics.

PMID- 30104517
TI  - Phylogenomic and Comparative Analyses of Complete Plastomes of Croomia and
      Stemona (Stemonaceae).
AB  - The monocot genus Croomia (Stemonaceae) comprises three herbaceous perennial
      species that exhibit EA (Eastern Asian)-ENA (Eastern North American) disjunct
      distribution. However, due to the lack of effective genomic resources, its
      evolutionary history is still weakly resolved. In the present study, we conducted
      comparative analysis of the complete chloroplast (cp) genomes of three Croomia
      species and two Stemona species. These five cp genomes proved highly similar in
      overall size (154,407-155,261 bp), structure, gene order and content. All five cp
      genomes contained the same 114 unique genes consisting of 80 protein-coding
      genes, 30 tRNA genes and 4 rRNA genes. Gene content, gene order, AT content and
      IR/SC boundary structures were almost the same among the five Stemonaceae cp
      genomes, except that the Stemona cp genome was found to contain an inversion in
      cemA and petA. The lengths of five genomes varied due to contraction/expansion of
      the IR/SC borders. A/T mononucleotides were the richest Simple Sequence Repeats
      (SSRs). A total of 46, 48, 47, 61 and 60 repeats were identified in C. japonica,
      C. heterosepala, C. pauciflora, S. japonica and S. mairei, respectively. A
      comparison of pairwise sequence divergence values across all introns and
      intergenic spacers revealed that the ndhF-rpl32, psbM-trnD and trnS-trnG regions
      are the fastest-evolving regions. These regions are therefore likely to be the
      best choices for molecular evolutionary and systematic studies at low taxonomic
      levels in Stemonaceae. Phylogenetic analyses of the complete cp genomes and 78
      protein-coding genes strongly supported the monophyly of Croomia. Two Asian
      species were identified as sisters that likely diverged in the Early Pleistocene
      (1.62 Mya, 95% HPD: 1.125-2.251 Mya), whereas the divergence of C. pauciflora
      dated back to the Late Miocene (4.77 Mya, 95% HPD: 3.626-6.162 Mya). The
      availability of these cp genomes will provide valuable genetic resources for
      further population genetics and phylogeographic studies on Croomia.

PMID- 30104520
TI  - Soybean- and Lupin-Derived Peptides Inhibit DPP-IV Activity on In Situ Human
      Intestinal Caco-2 Cells and Ex Vivo Human Serum.
AB  - Recent investigations have focused on food-derived peptides as novel natural
      inhibitors of dipeptidyl peptidase IV (DPP-IV), a new target for diabetes. This
      study aimed to optimize fast, sensitive, and cost-effective DPP-IV assays in situ
      on human intestinal Caco-2 cells and ex vivo on human serum. Both assays were
      applied to investigate the inhibitory activity of soy and lupin peptides. The
      best conditions for in situ DPP-IV activity in Caco-2 cells were obtained using 2
      day cells and 50 uM Gly-Pro-AMC. Sitagliptin, used as reference inhibitor, showed
      a dose-dependent response with a 50% inhibition concentration (IC50) of 0.6 uM. A
      lower IC50 (0.2 uM) was obtained for sitagliptin on human serum incubated with
      the substrate for 24 h. Both assays were applied to assess the activity of Lup1
      (LTFPGSAED) and Soy1 (IAVPTGVA) on DPP-IV. Lup1 and Soy1 inhibited DPP-IV in
      situ, with IC50 values of of 207.5 and 223.2 uM, respectively, and maintained
      their inhibitory activity ex vivo on circulating DPP-IV with a slightly lower
      potency. These assays can be used to characterize the DPP-IV inhibitory activity
      of food-derived molecules more accurately than in vitro biochemical tests. This
      combined approach also considers their effects on the circulating form of DPP-IV,
      correlated to metabolic diseases.

PMID- 30104521
TI  - Fundamental Motor Skills of Children in Deprived Areas of England: A Focus on
      Age, Gender and Ethnicity.
AB  - This study compared the mastery of fundamental motor skills (FMS) of males and
      females in early-childhood (four to five years, n = 170) and in middle-childhood
      (nine to ten years, n = 109) who attend schools in deprived and ethnically
      diverse areas of England. Process FMS (object control and locomotor skills) were
      observed using the Test of Gross Motor Development-2. Sprint speed over 10 meters
      and jump distance assessments were conducted using light gates and tape measures.
      A gender (male vs. female) by year-group (early-childhood vs. middle-childhood)
      interaction was shown for the process and product-oriented FMS measurements.
      Middle-childhood males and females demonstrated significantly greater FMS
      mastery, as compared to early-childhood (p < 0.05). Furthermore, middle-childhood
      males demonstrated significantly greater mastery of total FMS, object control
      skills, and product-oriented assessments, in comparison to females (p < 0.05).
      Children of Black and White ethnic groups achieved significantly greater mastery
      of locomotor skills, compared to Asian children, though this did not differ by
      year-group (p < 0.05). The results suggest that FMS development in deprived and
      ethnically diverse areas in England varies between genders during middle
      childhood and ethnicity. Thus, interventions addressing the lack of FMS mastery
      achievement, shown in middle-childhood girls and children from Asian ethnic
      backgrounds, may be pivotal. Further exploration of the role of ethnicity would
      provide greater clarity in approaching interventions to improve FMS.

PMID- 30104522
TI  - Poultry Slaughterhouse Wastewater Treatment Using Submerged Fibers in an Attached
      Growth Sequential Batch Reactor.
AB  - In this study, a sequential batch reactor (SBR) with different types of fibers
      was employed for the treatment of poultry slaughterhouse wastewater. Three types
      of fibers, namely, juite fiber (JF), bio-fringe fiber (BF), and siliconised
      conjugated polyester fiber (SCPF), were used. Four SBR experiments were
      conducted, using the fibers in different reactors, while the fourth reactor used
      a combination of these fibers. The treatment efficiency of the different reactors
      with and without fibers on biochemical oxygen demand (BOD), chemical oxygen
      demand (COD), ammonia-nitrogen (NH3-N), phosphorus (P), nitrite (NO2), nitrate
      (NO3), total suspended solids (TSS), and oil-grease were evaluated. The removal
      efficiency for the reactors with fibers was higher than that of the reactor
      without fibers for all pollutants. The treated effluent had 40 mg/L BOD5 and 45
      mg/L COD with an average removal efficiency of 96% and 93%, respectively, which
      meet the discharge limits stated in the Environmental Quality Act in Malaysia.

PMID- 30104525
TI  - Understanding of BeCu Interaction Characteristics with a Variation of ns Laser
      Pulse Duration.
AB  - An inspection process using a Spring Contact Probe (SCP) is an essential step in
      the semiconductor-manufacturing process. Many plungers, which are the main body
      of the SCP, are manufactured by a stamping process. After the stamping process,
      mechanical cutting is applied and the plunger body may be damaged. Thus, to
      improve cut quality and productivity while minimizing body damage, laser spot
      cutting can be used. To fully utilize this technology, it is necessary to
      investigate interaction characteristics of beryllium copper (BeCu) during laser
      spot cutting. Effects of a total irradiated laser-pulse energy (1 mJ ~1000 mJ )
      and pulse duration (100 ns ~8 ns ) on the material-removal zone, thermal depth,
      and crater size are examined. The crater size can be affected by the localization
      of heating dominantly. An incubation model is applied to investigate the
      correlation between crater size and laser-pulse energy. Surface morphology
      characteristics such as edge separation, small particles, spatter motion, and
      soaring-up motion are observed.

PMID- 30104524
TI  - Emergency and Mental Health Nurses' Perceptions and Attitudes towards Alcoholics.
AB  - Knowing professionals' attitudes is the basis for the development of skills for
      dealing with drug dependence. These attitudes may affect patients' clinical
      safety and the cost-benefit ratio of the interventions. The goal of this study
      was to assess emergency and mental health nurses' attitudes and perceptions
      towards alcoholics. A multicenter prospective descriptive study was conducted in
      six hospitals with 167 emergency and mental health nurses. Nurses classified
      alcoholics as sick individuals, although there was a tendency to feel
      uncomfortable working with them. Results indicated that these professionals had a
      rejecting attitude towards moderate alcohol consumption. It found that there was
      a significant association between the attitude of the nurse and gender, with the
      degree of rejection towards the alcoholic being higher in men than in women, and
      with less punitive attitudes in professionals with 0 to 11 years of professional
      experience.

PMID- 30104523
TI  - Nutritional and Environmental Factors in Thyroid Carcinogenesis.
AB  - Several epidemiological studies suggest an increased incidence of thyroid
      carcinoma (TC) in recent years, especially for the papillary histotype (PTC),
      suggesting that specific carcinogens might promote molecular abnormalities that
      are typical of PTC. The increased incidence is probably attributed to more
      intensive and sensitive diagnostic procedures, even if recent data suggest that
      various toxic elements could explain the phenomenon. Ionizing radiation exposure
      represents the most accepted risk factor for differentiated thyroid cancer that
      includes both the follicular and papillary histotypes. In this review, we
      examined the other environmental carcinogens that play a role in TC, such as
      eating habits, living in volcanic areas, and xenobiotic elements. Among eating
      habits, iodine intake represents one of the more discussed elements, because its
      deficiency is associated with follicular thyroid carcinomas (FTCs), while its
      progressive increment seems to be responsible for PTC. The gas, ash, and lava
      emissions of volcanoes are composed of various toxic compounds that pollute
      ground water, vegetables, and animals, contaminating humans via the food chain.
      Finally, the risk of developing PTC has also been associated with exposure of the
      population to xenobiotics in the environment or in the home. Their carcinogenic
      effects are probably caused by their accumulation, but additional studies are
      necessary to better understand the mechanisms of action.

PMID- 30104526
TI  - Grief and Avoidant Death Attitudes Combine to Predict the Fading Affect Bias.
AB  - The fading affect bias (FAB) occurs when unpleasant affect fades faster than
      pleasant affect. To detect mechanisms that influence the FAB in the context of
      death, we measured neuroticism, depression, anxiety, negative religious coping,
      death attitudes, and complicated grief as potential predictors of FAB for
      unpleasant/death and pleasant events at 2 points in time. The FAB was robust
      across older and newer events, which supported the mobilization-minimization
      hypothesis. Unexpectedly, complicated grief positively predicted FAB, and death
      avoidant attitudes moderated this relation, such that the Initial Event Affect by
      Grief interaction was only significant at the highest 3 quintiles of death
      avoidant attitudes. These results were likely due to moderate grief ratings,
      which were, along with avoidant death attitudes, related to healthy outcomes in
      past research. These results implicate complicated grief and death avoidant
      attitudes as resiliency mechanisms that are mobilized during bereavement to
      minimize its unpleasant effects.

PMID- 30104529
TI  - Design, Implementation and Practical Evaluation of an IoT Home Automation System
      for Fog Computing Applications Based on MQTT and ZigBee-WiFi Sensor Nodes.
AB  - In recent years, the improvement of wireless protocols, the development of cloud
      services and the lower cost of hardware have started a new era for smart homes.
      One such enabling technologies is fog computing, which extends cloud computing to
      the edge of a network allowing for developing novel Internet of Things (IoT)
      applications and services. Under the IoT fog computing paradigm, IoT gateways are
      usually utilized to exchange messages with IoT nodes and a cloud. WiFi and ZigBee
      stand out as preferred communication technologies for smart homes. WiFi has
      become very popular, but it has a limited application due to its high energy
      consumption and the lack of standard mesh networking capabilities for low-power
      devices. For such reasons, ZigBee was selected by many manufacturers for
      developing wireless home automation devices. As a consequence, these technologies
      may coexist in the 2.4 GHz band, which leads to collisions, lower speed rates and
      increased communications latencies. This article presents ZiWi, a distributed fog
      computing Home Automation System (HAS) that allows for carrying out seamless
      communications among ZigBee and WiFi devices. This approach diverges from
      traditional home automation systems, which often rely on expensive central
      controllers. In addition, to ease the platform's building process, whenever
      possible, the system makes use of open-source software (all the code of the nodes
      is available on GitHub) and Commercial Off-The-Shelf (COTS) hardware. The initial
      results, which were obtained in a number of representative home scenarios, show
      that the developed fog services respond several times faster than the evaluated
      cloud services, and that cross-interference has to be taken seriously to prevent
      collisions. In addition, the current consumption of ZiWi's nodes was measured,
      showing the impact of encryption mechanisms.

PMID- 30104527
TI  - Chalcones Repressed the AURKA and MDR Proteins Involved in Metastasis and
      Multiple Drug Resistance in Breast Cancer Cell Lines.
AB  - In the present investigation, trans-chalcone and licochalcone A were tested
      against MCF-7 and BT-20 breast cancer cell lines for anti-tumor activity. We
      found that both chalcones down regulated important genes associated to cancer
      development and inhibited cell migration of metastatic cells (BT-20). Finally, we
      observed that licochalcone A reduces the MDR-1 protein, while both chalcones
      suppress the AURKA protein in a dose-dependent manner. In conclusion, we observed
      the trans-chalcone and licochalcone A affected the cell viability of breast
      cancer cell lines MCF-7 and BT-20 and presents anti-metastatic and anti
      resistance potential, by the repression of AUKA and MDR-1 proteins.

PMID- 30104528
TI  - Berberine Inhibits Human Melanoma A375.S2 Cell Migration and Invasion via
      Affecting the FAK, uPA, and NF-kappaB Signaling Pathways and Inhibits PLX4032
      Resistant A375.S2 Cell Migration In Vitro.
AB  - Many studies have demonstrated that berberine inhibited the cell migration and
      invasion in human cancer cell lines. However, the exact molecular mechanism of
      berberine inhibiting the cell migration and invasion of human melanoma A375.S2
      and A375.S2/PLX (PLX4032 induced resistant A375.S2) skin cancer cells remains
      unknown. In this study, we investigated the anti-metastasis mechanisms of
      berberine in human melanoma cancer A375.S2 cells and A375.S2/PLX resistant cells
      in vitro. Berberine at low concentrations (0, 1, 1.5 and 2 MUM) induced cell
      morphological changes and reduced the viable cell number and inhibited the
      mobility, migration, and invasion of A375.S2 cells that were assayed by wound
      healing and transwell filter. The gelatin zymography assay showed that berberine
      slightly inhibited MMP-9 activity in A375.S2 cells. Results from western blotting
      indicated that berberine inhibited the expression of MMP-1, MMP-13, E-cadherin, N
      cadherin, RhoA, ROCK1, SOS-1, GRB2, Ras, p-ERK1/2, p-c-Jun, p-FAK, p-AKT, NF
      kappaB, and uPA after 24 h of treatment, but increased the PKC and PI3K in
      A375.S2 cells. PLX4032 is an inhibitor of the BRAFV600E mutation and used for the
      treatment of cancer cells harboring activated BRAF mutations. Berberine decrease
      cell number and inhibited the cell mobility in the resistant A375.S2
      (A375.S2/PLX, PLX4032 generated resistant A375.S2 cells). Based on these
      observations, we suggest that the potential of berberine as an anti-metastatic
      agent in melanoma that deserves to be investigated in more detail, including in
      vivo studies in future.

PMID- 30104530
TI  - CD147 and Cyclooxygenase Expression in Feline Oral Squamous Cell Carcinoma.
AB  - Feline oral squamous cell carcinoma (OSCC) is a highly invasive form of cancer in
      cats. In human OSCC, cluster of differentiation 147 (CD147) contributes to
      inflammation and tumor invasiveness. CD147 is a potential therapeutic target, but
      the expression of CD147 in feline OSCC has not been examined.
      Immunohistochemistry was used to determine if cyclooxygenase 2 (COX-2) and CD147
      expression in feline OSCC biopsies was coordinated. Tumor cells were more likely
      to express COX-2 (22/43 cases or 51%) compared to stroma (8/43 or 19%) and
      adjacent oral epithelium (9/31 cases or 29%) (p < 0.05). CD147 was also more
      likely to occur in tumor cells compared to stroma and adjacent mucosa, with 21/43
      (49%) of cases having >50% tumor cells with mild or moderate CD147 expression,
      compared to 9/28 (32%) in adjacent epithelium and only 5/43 (12%) in adjacent
      stroma (p < 0.05). In feline OSCC cell lines (SCCF1, SCCF2, and SCCF3), CD147
      gene expression was more consistently expressed compared to COX-2, which was 60
      fold higher in SCCF2 cells compared to SCCF1 cells (p < 0.05). CD147 expression
      did not correlate with COX-2 expression and prostaglandin E2 (PGE2) secretion,
      indicating that they may be independently regulated. CD147 potentially represents
      a novel therapeutic target for the treatment of feline OSCC and further study of
      CD147 is warranted.

PMID- 30104531
TI  - Involvement of Osteocytes in the Action of Pasteurella multocida Toxin.
AB  - Pasteurella multocida toxin (PMT) causes progressive atrophic rhinitis with
      severe turbinate bone degradation in pigs. It has been reported that the toxin
      deamidates and activates heterotrimeric G proteins, resulting in increased
      differentiation of osteoclasts and blockade of osteoblast differentiation. So
      far, the action of PMT on osteocytes, which is the most abundant cell type in
      bone tissue, is not known. In MLO-Y4 osteocytes, PMT deamidated heterotrimeric G
      proteins, resulting in loss of osteocyte dendritic processes, stress fiber
      formation, cell spreading and activation of RhoC but not of RhoA. Moreover, the
      toxin caused processing of membrane-bound receptor activator of NF-kappaB ligand
      (RANKL) to release soluble RANKL and enhanced the secretion of osteoclastogenic
      TNF-alpha. In a co-culture model of osteocytes and bone marrow cells, PMT-induced
      osteoclastogenesis was largely increased as compared to the mono-culture model.
      The enhancement of osteoclastogenesis observed in the co-culture was blocked by
      sequestering RANKL with osteoprotegerin and by an antibody against TNF-alpha
      indicating involvement of release of the osteoclastogenic factors from
      osteocytes. Data support the crucial role of osteocytes in bone metabolism and
      osteoclastogenesis and identify osteocytes as important target cells of PMT in
      progressive atrophic rhinitis.

PMID- 30104532
TI  - Investigation of Position Sensing and Energy Harvesting of a Flexible
      Triboelectric Touch Pad.
AB  - Triboelectric nanogenerator (TENG) is a promising technology because it can
      harvest energy from the environment to enable self-sustainable mobile and
      wearable electronic devices. In this work, we present a flexible touch pad
      capable of detecting the contact location of an object and generating substantial
      energy simultaneously based on the coupling of triboelectric effects and
      electrostatic induction. The touch pad consists of Polytetrafluoroethylene (PTFE)
      thin film, multiple Aluminum (Al) electrodes and Polyethylene terephthalate (PET)
      layers, which can be achieved through low cost, simplified and scalable
      fabrication process. Different from the conventional multi-pixel-based
      positioning sensor (i.e., large array of sensing elements and electrodes), the
      analogue method proposed here is used to implement the positioning function with
      only four electrodes. Position location can achieve a detecting resolution of as
      small as 1.3 mm (the size of locating layer is 7.5 cm * 7.5 cm). For the energy
      harvesting part, a multilayer structure is designed to provide higher current
      output. The open circuit voltage of the device is around 420 V and the short
      circuit current can reach up to 6.26 uA with current density of 0.25 uA/cm2. The
      maximum output power obtained is approximately 10 mW, which is 0.4 mW/cm2. The
      flexibility and significantly reduced number of electrodes enable the proposed
      touch pad to be readily integrated into portable electronic devices, such as
      intelligent robots, laptops, healthcare devices, and environmental surveys, etc.

PMID- 30104533
TI  - Fractional Frequency Reuse Scheme for Device to Device Communication Underlaying
      Cellular on Wireless Multimedia Sensor Networks.
AB  - Wireless multimedia sensor networks (WMSNs) have been improved with the increase
      of multimedia data. In WMSNs, a centralization problem can occur because of large
      size multimedia data. It is necessary to consider device-to-device (D2D)
      communication. We focus on D2D WMSN based on cellular networks. Sensors in the
      D2D WMSN can non-orthogonally use a cellular link, which is a wireless
      communication channel between a sensor and an aggregator, and a D2D link, which
      is the channel between sensors. As a result, it has more complex interference
      environments than an ordinary system. Therefore, it is a key factor to manage the
      varying inter-cell interference effectively for throughput improvement. We
      propose an interference mitigation scheme that can be applied to D2D WMSN. In the
      proposed scheme, a cell is separated into six zones and orthogonal frequency is
      allocated to each zone for cellular links. The frequencies allocated to cellular
      links are reused by D2D links of neighboring zones. The simulation results show
      that the throughput of the proposed scheme increases two times compared to a
      static frequency allocation scheme.

PMID- 30104535
TI  - A Mitochondrial Encoded Messenger at the Nucleus.
AB  - Mitochondria-nucleus (mitonuclear) retrograde signaling via nuclear import of
      otherwise mitochondrial targeted factors occurs during mitochondrial unfolded
      protein response (UPRmt), a mechanism that counters mitochondrial and cellular
      stresses. Other than nuclear encoded proteins, mitochondrial DNA (mtDNA)-encoded
      peptides, such as humanin, are known to have important pro-survival and metabolic
      regulatory functions. A recent report has indicated that another mtDNA-encoded
      peptide, the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c), could
      translocate into the nucleus upon stress induction. In the nucleus, MOTS-c binds
      to DNA and regulates the transcription of stress response genes in concert with
      other transcription factors. This is the first clear example of a mitochondria
      derived peptide (MDP) acting in the nucleus to affect transcriptional responses
      to stress. Thus, MOTS-c may bear some characteristics of a 'mitokine' factor that
      mediates mitohormesis, influencing cell survival as well as organismal health and
      longevity.

PMID- 30104534
TI  - Computational Molecular Docking and X-ray Crystallographic Studies of Catechins
      in New Drug Design Strategies.
AB  - Epidemiological and laboratory studies have shown that green tea and green tea
      catechins exert beneficial effects on a variety of diseases, including cancer,
      metabolic syndrome, infectious diseases, and neurodegenerative diseases. In most
      cases, (-)-epigallocatechin gallate (EGCG) has been shown to play a central role
      in these effects by green tea. Catechins from other plant sources have also shown
      health benefits. Many studies have revealed that the binding of EGCG and other
      catechins to proteins is involved in its action mechanism. Computational docking
      analysis (CMDA) and X-ray crystallographic analysis (XCA) have provided detailed
      information on catechin-protein interactions. Several of these studies have
      revealed that the galloyl moiety anchors it to the cleft of proteins through
      interactions with its hydroxyl groups, explaining the higher activity of
      galloylated catechins such as EGCG and epicatechin gallate than non-galloylated
      catechins. In this paper, we review the results of CMDA and XCA of EGCG and other
      plant catechins to understand catechin-protein interactions with the expectation
      of developing new drugs with health-promoting properties.

PMID- 30104536
TI  - Identification and Characterization of miRNAs in Self-Rooted and Grafted Malus
      Reveals Critical Networks Associated with Flowering.
AB  - Grafting can improve the agricultural traits of crop plants, especially fruit
      trees. However, the regulatory networks and differentially expressed microRNAs
      (miRNAs) related to grafting in apple remain unclear. Herein, we conducted high
      throughput sequencing and identified differentially expressed miRNAs among self
      rooted Fuji, self-rooted M9, and grafted Fuji/M9. We analyzed the flowering rate,
      leaf morphology, and nutrient and carbohydrate contents in the three materials.
      The flowering rate, element and carbohydrate contents, and expression levels of
      flowering genes were higher in Fuji/M9 than in Fuji. We detected 206 known miRNAs
      and 976 novel miRNAs in the three materials, and identified those that were up-
      or downregulated in response to grafting. miR156 was most abundant in Fuji,
      followed by Fuji/M9, and then self-rooted M9, while miR172 was most abundant in
      M9, followed by Fuji/M9, and then Fuji. These expression patterns suggest that
      that these miRNAs were related to grafting. A Gene Ontology (GO) analysis showed
      that the differentially expressed miRNAs controlled genes involved in various
      biological processes, including cellular biosynthesis and metabolism. The
      expression of differentially expressed miRNAs and flowering-related genes was
      verified by qRT-PCR. Altogether, this comprehensive analysis of miRNAs related to
      grafting provides valuable information for breeding and grafting of apple and
      other fruit trees.

PMID- 30104538
TI  - A Stability Indicating HPLC Method to Determine Actual Content and Stability of
      Nicotine within Electronic Cigarette Liquids.
AB  - (1) Background: Despite the growing use of e-cigarettes, in most countries, there
      is no regulation covering manufacturing standards of the solution ('e-liquid'),
      leading to concerns over the accuracy of labelling and stability of the products
      under a range of conditions. Following the United States (US) Food and Drug
      Administration (FDA) requirements for manufacture of e-liquids, we aimed to
      develop a simple high-performance liquid chromatography (HPLC) method to
      determine nicotine content in nicotine-containing e-liquids, even in the presence
      of degradation products; (2) Methods: We developed an HPLC method to quantify
      nicotine in the presence of the two major constituents of all e-liquids,
      glycerine and propylene glycol, and in the presence of degradation products; (3)
      Results: Our HPLC method performed strongly and was validated it according to
      international guidelines. For the e-liquids tested, nicotine content levels were
      all higher than labelled (up to 117.9 +/- 1.87% of the labelled content). While
      nicotine was shown to be unstable at 60  degrees C, it was stabilized at this
      temperature in the e-liquid formulations for up to 10 days; and (4) Conclusions:
      The HPLC method is suitable for adoption by laboratories to determine the actual
      content and stability of nicotine-containing products. The higher than labelled
      nicotine levels in e-liquids raises clinical and public health concerns.

PMID- 30104537
TI  - Potent HIV-1-Specific CD8 T Cell Responses Induced in Mice after Priming with a
      Multiepitopic DNA-TMEP and Boosting with the HIV Vaccine MVA-B.
AB  - An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the
      best solution to provide a sustainable control and/or eradication of the virus.
      We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara
      (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and
      therapeutic clinical trials, but was unable to prevent viral rebound after
      antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we
      described the design and immune responses elicited in mice by a new T cell multi
      epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous
      or heterologous prime/boost regimens in combination with MVA-B. The TMEP-B
      protein contained conserved regions from Gag, Pol, and Nef proteins including
      multiple CD4 and CD8 T cell epitopes functionally associated with HIV control.
      Heterologous DNA-TMEP/MVA-B regimen induced higher HIV-1-specific CD8 T cell
      responses with broader epitope recognition and higher polyfunctional profile than
      the homologous DNA-TMEP/DNA-TMEP or the heterologous DNA-GPN/MVA-B combinations.
      Moreover, higher HIV-1-specific CD4 and Tfh immune responses were also detected
      using this regimen. After MVA-B boost, the magnitude of the anti-VACV CD8 T cell
      response was significantly compromised in DNA-TMEP-primed animals. Our results
      revealed the immunological potential of DNA-TMEP prime/MVA-B boost regimen and
      supported the application of these combined vectors in HIV-1 prevention and/or
      therapy.

PMID- 30104539
TI  - Nutcracker Syndrome in Children: Role of Doppler Ultrasonographic Indices in
      Detecting the Pattern of Symptoms.
AB  - The purpose of this study was to evaluate the clinical characteristics of 44
      pediatric patients who were diagnosed as having nutcracker syndrome (NCS). We
      also investigated the left renal vein Doppler ultrasonography (DUS) results, to
      determine whether or not there was an association between clinical symptoms and
      DUS findings among these patients. The clinical data from 44 pediatric patients
      who were diagnosed as having NCS from January 2008 to December 2015 were
      retrospectively reviewed. We grouped the patients according to the presenting
      symptoms as symptomatic (loin pain; macroscopic hematuria or both) and non
      symptomatic (microscopic hematuria and proteinuria were detected incidentally)
      and evaluated the left renal vein DUS indices in these two groups separately.
      Asymptomatic NCS was found in 27 (61.4%) patients; 21 (47.7%) of whom were
      admitted for the evaluation of proteinuria. The most frequent presenting symptoms
      were left flank pain (20.5%) and macroscopic hematuria (13.6%); and 2 (4.5%)
      patients presented with a combination of left flank pain and macroscopic
      hematuria. The mean ratio of the diameter of the hilar portion of the left renal
      vein (LRV) to that of the aortomesenteric portion was 4.36 +/- 1.55. The mean
      ratio of the peak velocity (PV) between the two sites of the LRV was 7.32 +/-
      2.68 (3.1-15.6). The differences in the ratio of the diameters were statistically
      significant between the two groups and significantly higher in children with
      asymptomatic NCS (p = 0.025). The PV ratios of the LRV (p = 0.035) were
      significantly higher in asymptomatic children with NCS than in the symptomatic
      group. Our study identifies that increased compression ratio of the LRV
      entrapment is most observed in orthostatic proteinuria and microscopic hematuria.

PMID- 30104540
TI  - Motion Blurred Star Image Restoration Based on MEMS Gyroscope Aid and Blur Kernel
      Correction.
AB  - Under dynamic conditions, motion blur is introduced to star images obtained by a
      star sensor. Motion blur affects the accuracy of the star centroid extraction and
      the identification of stars, further reducing the performance of the star sensor.
      In this paper, a star image restoration algorithm is investigated to reduce the
      effect of motion blur on the star image. The algorithm includes a blur kernel
      calculation aided by a MEMS gyroscope, blur kernel correction based on the
      structure of the star strip, and a star image reconstruction method based on
      scaled gradient projection (SGP). Firstly, the motion trajectory of the star spot
      is deduced, aided by a MEMS gyroscope. Moreover, the initial blur kernel is
      calculated by using the motion trajectory. Then, the structure information star
      strip is extracted by Delaunay triangulation. Based on the structure information,
      a blur kernel correction method is presented by utilizing the preconditioned
      conjugate gradient interior point algorithm to reduce the influence of bias and
      installation deviation of the gyroscope on the blur kernel. Furthermore, a speed
      up image reconstruction method based on SGP is presented for time-saving.
      Simulated experiment results demonstrate that both the blur kernel determination
      and star image reconstruction methods are effective. A real star image experiment
      shows that the accuracy of the star centroid extraction and the number of
      identified stars increase after restoration by the proposed algorithm.

PMID- 30104543
TI  - Efficient CdTe Nanocrystal/TiO2 Hetero-Junction Solar Cells with Open Circuit
      Voltage Breaking 0.8 V by Incorporating A Thin Layer of CdS Nanocrystal.
AB  - Nanocrystal solar cells (NCs) allow for large scale solution processing under
      ambient conditions, permitting a promising approach for low-cost photovoltaic
      products. Although an up to 10% power conversion efficiency (PCE) has been
      realized with the development of device fabrication technologies, the open
      circuit voltage (Voc) of CdTe NC solar cells has stagnated below 0.7 V, which is
      significantly lower than most CdTe thin film solar cells fabricated by vacuum
      technology (around 0.8 V~0.9 V). To further improve the NC solar cells'
      performance, an enhancement in the Voc towards 0.8-1.0 V is urgently required.
      Given the unique processing technologies and physical properties in CdTe NC, the
      design of an optimized band alignment and improved junction quality are important
      issues to obtain efficient solar cells coupled with high Voc. In this work, an
      efficient method was developed to improve the performance and Voc of solution
      processed CdTe nanocrystal/TiO2 hetero-junction solar cells. A thin layer of
      solution-processed CdS NC film (~5 nm) as introduced into CdTe NC/TiO2 to
      construct hetero-junction solar cells with an optimized band alignment and p-n
      junction quality, which resulted in a low dark current density and reduced
      carrier recombination. As a result, devices with improved performance (5.16%
      compared to 2.63% for the control device) and a Voc as high as 0.83 V were
      obtained; this Voc value is a record for a solution-processed CdTe NC solar cell.

PMID- 30104542
TI  - Sol-gel Silica Nanoparticles in Medicine: A Natural Choice. Design, Synthesis and
      Products.
AB  - Silica is one of the most abundant minerals in the Earth's crust, and over time
      it has been introduced first into human life and later into engineering. Silica
      is present in the food chain and in the human body. As a biomaterial, silica is
      widely used in dentistry, orthopedics, and dermatology. Recently amorphous sol
      gel SiO2 nanoparticles (NPs) have appeared as nanocarriers in a wide range of
      medical applications, namely in drug/gene target delivery and imaging diagnosis,
      where they stand out for their high biocompatibility, hydrophilicity, enormous
      flexibility for surface modification with a high payload capacity, and prolonged
      blood circulation time. The sol-gel process is an extremely versatile bottom-up
      methodology used in the synthesis of silica NPs, offering a great variety of
      chemical possibilities, such as high homogeneity and purity, along with full
      scale pH processing. By introducing organic functional groups or surfactants
      during the sol-gel process, ORMOSIL NPs or mesoporous NPs are produced. Colloidal
      route, biomimetic synthesis, solution route and template synthesis (the main sol
      gel methods to produce monosized silica nanoparticles) are compared and
      discussed. This short review goes over some of the emerging approaches in the
      field of non-porous sol-gel silica NPs aiming at medical applications, centered
      on the syntheses processes used.

PMID- 30104544
TI  - Cell Therapy in Idiopathic Pulmonary Fibrosis?.
AB  - Idiopathic pulmonary fibrosis is a fatal disease with no effective or curative
      treatment options. In recent decades, cell-based therapies using stem cells or
      lung progenitor cells to regenerate lung tissue have experienced rapid growth in
      both preclinical animal models and translational clinical studies. In this
      review, the current knowledge of these cell therapies is summarized. Although
      further investigations are required, these studies indicate that cell therapies
      are a promising therapeutic approach for the treatment of idiopathic pulmonary
      fibrosis.

PMID- 30104545
TI  - Effects of Caffeine on Myocardial Blood Flow: A Systematic Review.
AB  - BACKGROUND: Caffeine is one of the most widely consumed stimulants worldwide. It
      is a well-recognized antagonist of adenosine and a potential cause of false
      negative functional measurements during vasodilator myocardial perfusion. The aim
      of this systematic review is to summarize the evidence regarding the effects of
      caffeine intake on functional measurements of myocardial perfusion in patients
      with suspected coronary artery disease. Pubmed, Web of Science, and Embase were
      searched using a predefined electronic search strategy. Participants-healthy
      subjects or patients with known or suspected CAD. Comparisons-recent caffeine
      intake versus no caffeine intake. Outcomes-measurements of functional myocardial
      perfusion. Study design-observational. Fourteen studies were deemed eligible for
      this systematic review. There was a wide range of variability in study design
      with varying imaging modalities, vasodilator agents, serum concentrations of
      caffeine, and primary outcome measurements. The available data indicate a
      significant influence of recent caffeine intake on cardiac perfusion measurements
      during adenosine and dipyridamole induced hyperemia. These effects have the
      potential to affect the clinical decision making by re-classification to
      different risk-categories.

PMID- 30104541
TI  - Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current
      Understanding and Future Therapeutic Strategies.
AB  - Endometriosis is an estrogen-dependent inflammatory disease that affects up to
      10% of women of reproductive age and accounts for up to 50% of female infertility
      cases. It has been highly associated with poorer outcomes of assisted
      reproductive technology (ART), including decreased oocyte retrieval, lower
      implantation, and pregnancy rates. A better understanding of the pathogenesis of
      endometriosis-associated infertility is crucial for improving infertility
      treatment outcomes. Current theories regarding how endometriosis reduces
      fertility include anatomical distortion, ovulatory dysfunction, and niche
      inflammation-associated peritoneal or implantation defects. This review will
      survey the latest evidence on the role of inflammatory niche in the peritoneal
      cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment
      strategies that target these inflammation processes are also included.
      Furthermore, mesenchymal stem cell-based therapies are highlighted for potential
      endometriosis treatment because of their immunomodulatory effects and tropism
      toward inflamed lesion foci. Potential applications of stem cell therapy in
      treatment of endometriosis-associated infertility in particular for safety and
      efficacy are discussed.

PMID- 30104546
TI  - Level of and Factors Determining Physical Activity in Students in Ukraine and the
      Visegrad Countries.
AB  - Background: Examining the level of physical activity in students is a vital issue
      as these young people are the future social elite. Methods: The research was
      conducted in the years 2013-2016 and comprised 5008 males and females, mean age
      of 20.5 +/- 2.1 years, including 2237 (55.3%) students from students from Eastern
      European National University, Lutsk, and Ternopil State Medical University,
      Ukraine, as well as 2237 (44.7%) from the Visegrad countries, i.e., University of
      Pecs in Hungary, University in Kosice, Slovakia, University of Olomunec in the
      Czech Republic and the State School of Higher Education in Biala Podlaska,
      Poland. It applied a diagnostic survey-the extended version of the International
      Physical Activity Questionnaire (IPAQ), supplemented with original questions
      regarding body weight, height, self-assessment of physical fitness and amount of
      leisure time. Results: The comparison of students' PA from selected European
      countries, members of the Visegrad group and Ukraine, is particularly vital to
      the latter country as it demonstrates a different level of socio-economic
      development. There was noted a significantly higher level of physical activity in
      students from the Visegrad countries than in Ukraine. Further, there was an
      overall lower level of physical activity in females compared to males. What was
      positive about the studied samples was a healthy BMI index in the majority of the
      male and female respondents, with a significantly higher indicator in Ukraine.
      Conclusions: Among the factors significantly affecting higher physical activity
      in both researched samples were the BMI and high self-assessment of physical
      fitness. There was no significant variation in the level of physical activity and
      the amount of leisure time, both in those studying in the Visegrad states and
      Ukraine.

PMID- 30104548
TI  - Molecular Verification of Bloom-forming Aphanizomenon flos-aquae and Their
      Secondary Metabolites in the Nakdong River.
AB  - Aphanizomenon spp. have formed harmful cyanobacterial blooms in the Nakdong River
      during spring, autumn, and now in winter, and the expansion of blooming period
      and area, associated with the global warming is predicted. The genus
      Aphanizomenon has been described to produce harmful secondary metabolites such as
      off-flavors and cyanotoxins. Therefore, the production of harmful secondary
      metabolites from the Aphanizomenon blooms in the Nakdong River needs to be
      monitored to minimize the risk to both water quality and public health. Here, we
      sampled the cyanobacterial blooms in the Nakdong River and isolated ten
      Aphanizomenon strains, morphologically classified as Aphanizomenon flos-aquae
      Ralfs ex Bornet et Flahault 1888. Phylogenetic analysis using 16S rRNA and
      internal transcribed spacer (ITS) region nucleotide sequences confirmed this
      classification. We further verified the harmful secondary metabolites-producing
      potential of A. flos-aquae isolates and water samples containing cyanobacterial
      blooms using PCR with specific primer sets for genes involved in biosynthesis of
      off-flavor metabolites (geosmin) and toxins (microcystins, saxitoxins and
      cylindrospermopsins). It was confirmed that these metabolite biosynthesis genes
      were not identified in all isolates and water samples containing only
      Aphanizomenon spp. Thus, it is likely that there is a low potential for the
      production of off-flavor metabolites and cyanotoxins in Aphanizomenon blooms in
      the Nakdong River.

PMID- 30104547
TI  - Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial
      Thrombosis In Vivo by Morin Hydrate.
AB  - Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and
      apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in
      which platelet activation plays a major role. This study investigated the effect
      of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate
      markedly inhibited platelet aggregation stimulated by collagen in human platelets
      but not that stimulated by other agonists. In collagen-activated platelets, morin
      hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+
      mobilization; P-selectin expression; and phosphorylation of phospholipase Cgamma2
      (PLCgamma2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase
      (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation,
      except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH. signals
      in platelet suspensions but not in the cell-free system (Fenton reaction
      solution). Moreover, morin hydrate substantially increased the occlusion time of
      thrombotic platelet plug formation but had no effect on bleeding time in mice. In
      conclusion, morin hydrate crucially inhibits platelet activation through
      inhibition of the PLCgamma2-PKC cascade and subsequent suppression of Akt and
      MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore,
      this paper suggests that morin hydrate constitutes a novel and potential natural
      therapeutic product for preventing or treating thromboembolic disorders.

PMID- 30104550
TI  - Oryzines A & B, Maleidride Congeners from Aspergillus oryzae and Their Putative
      Biosynthesis.
AB  - Aspergillus oryzae is traditionally used in East Asia for the production of food
      and brewing. In addition, it has been developed into a suitable host for the
      heterologous expression of natural product biosynthetic genes and gene clusters,
      enabling the functional analysis of the encoded enzymes. A. oryzae shares a 99.5%
      genome homology with Aspergillus flavus, but their secondary metabolomes differ
      significantly and various compounds unique to A. oryzae have been reported. While
      using A. oryzae as a host for heterologous expression experiments we discovered
      two new metabolites in extracts of A. oryzae M-2-3 with an unusual maleidride
      backbone, which were named oryzine A and B. Their structures were elucidated by
      high resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR)
      analysis. Their structural relationships with known maleidrides implied
      involvement of a citrate synthase (CS) and a polyketide (PKS) or fatty acid
      synthase (FAS) in their biosynthesis. Analysis of the A. oryzae genome revealed a
      single putative biosynthetic gene cluster (BGC) consistent with the hypothetical
      biosynthesis of the oryzines. These findings increase knowledge of the chemical
      potential of A. oryzae and are the first attempt to link a novel product of this
      fungus with genomic data.

PMID- 30104549
TI  - Synthesis, Characterization, and In Vitro Cancer Cell Growth Inhibition
      Evaluation of Novel Phosphatidylcholines with Anisic and Veratric Acids.
AB  - Phenolic acids and its methoxy derivatives are known to induce caspase-mediated
      apoptosis activity and exhibit cytotoxic effect towards various cancer cell
      lines. However, their low stability and poor bioavailability in the human
      organism extensively restrict the utility of this group of compounds as
      anticancer and health-promoting agents. In this report, a series of eight novel
      phosphatidylcholines (3a-b, 5a-b, 7a-b, 8a-b) containing anisic or veratric acids
      (1a-b) at sn-1 and/or sn-2 positions were synthesized. The phenoylated
      phospholipids were obtained in good yields 28-66%. The structures of novel
      compounds were determined by their spectroscopic data. All synthesized compounds
      were evaluated for their antiproliferative activity towards six cancer cell lines
      and normal cell line Balb/3T3. Lipophilization of phenolcarboxylic acids
      significantly increased their anticancer properties. The asymmetrically
      substituted phenoylated phosphatidylcholines exhibited higher antiproliferative
      effect than free acids. Lysophosphatidylcholine (7b) effectively inhibited the
      proliferation of human leukaemia (MV4-11), breast (MCF-7), and colon (LoVo)
      cancer cell lines at concentrations of 9.5-20.7 um and was from 19 to 38-fold
      more active than corresponding free veratric acid. The conjugation of
      anisic/veratric acids with the phosphatidylcholine have proved the anticancer
      potential of these phenolcarboxylic acids and showed that this type of
      lipophilization is an effective method for the production of active biomolecules.

PMID- 30104551
TI  - Reported Direct and Indirect Contact with Dromedary Camels among Laboratory
      Confirmed MERS-CoV Cases.
AB  - Dromedary camels (Camelus dromedarius) are now known to be the vertebrate animal
      reservoir that intermittently transmits the Middle East respiratory syndrome
      coronavirus (MERS-CoV) to humans. Yet, details as to the specific mechanism(s) of
      zoonotic transmission from dromedaries to humans remain unclear. The aim of this
      study was to describe direct and indirect contact with dromedaries among all
      cases, and then separately for primary, non-primary, and unclassified cases of
      laboratory-confirmed MERS-CoV reported to the World Health Organization (WHO)
      between 1 January 2015 and 13 April 2018. We present any reported dromedary
      contact: direct, indirect, and type of indirect contact. Of all 1125 laboratory
      confirmed MERS-CoV cases reported to WHO during the time period, there were 348
      (30.9%) primary cases, 455 (40.4%) non-primary cases, and 322 (28.6%)
      unclassified cases. Among primary cases, 191 (54.9%) reported contact with
      dromedaries: 164 (47.1%) reported direct contact, 155 (44.5%) reported indirect
      contact. Five (1.1%) non-primary cases also reported contact with dromedaries.
      Overall, unpasteurized milk was the most frequent type of dromedary product
      consumed. Among cases for whom exposure was systematically collected and reported
      to WHO, contact with dromedaries or dromedary products has played an important
      role in zoonotic transmission.

PMID- 30104552
TI  - Effects of Rhizome Extract of Dioscorea batatas and Its Active Compound,
      Allantoin, on the Regulation of Myoblast Differentiation and Mitochondrial
      Biogenesis in C2C12 Myotubes.
AB  - With the aging process, a loss of skeletal muscle mass and dysfunction related to
      metabolic syndrome is observed in older people. Yams are commonly use in
      functional foods and medications with various effects. The present study was
      conducted to investigate the effects of rhizome extract of Dioscorea batatas
      (Dioscoreae Rhizoma, Chinese yam) and its bioactive compound, allantoin, on
      myoblast differentiation and mitochondrial biogenesis in skeletal muscle cells.
      Yams were extracted in water and allantoin was analyzed by high performance
      liquid chromatography (HPLC). The expression of myosin heavy chain (MyHC) and
      mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated
      receptor gamma coactivator 1-alpha (PGC-1alpha), sirtuin-1 (Sirt-1), nuclear
      respiratory factor-1 (NRF-1) and transcription factor A, mitochondrial (TFAM),
      and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA
      carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)
      polymerase chain reaction (RT-PCR) or western blot. The glucose levels and total
      ATP contents were measured by glucose consumption, glucose uptake and ATP assays,
      respectively. Treatment with yam extract (1 mg/mL) and allantoin (0.2 and 0.5 mM)
      significantly increased MyHC expression compared with non-treated myotubes. Yam
      extract and allantoin significantly increased the expression of PGC-1alpha, Sirt
      1, NRF-1 and TFAM, as well as the phosphorylation of AMPK and ACC in C2C12
      myotubes. Furthermore, yam extract and allantoin significantly increased glucose
      uptake levels and ATP contents. Finally, HPLC analysis revealed that the yam
      water extract contained 1.53% of allantoin. Yam extract and allantoin stimulated
      myoblast differentiation into myotubes and increased energy production through
      the upregulation of mitochondrial biogenesis regulators. These findings indicate
      that yam extract and allantoin can help to prevent skeletal muscle dysfunction
      through the stimulation of the energy metabolism.

PMID- 30104553
TI  - Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and
      Insulin Resistance in Obesity.
AB  - Epigenetic marks, and especially DNA methylation, are becoming an important
      factor in obesity, which could help to explain its etiology and associated
      comorbidities. Adipose tissue, now considered as an important endocrine organ,
      produces complement system factors. Complement component 3 (C3) turns out to be
      an important protein in metabolic disorders, via either inflammation or the C3
      subproduct acylation stimulating protein (ASP) which directly stimulates lipid
      storage. In this study, we analyze C3 DNA methylation in adipose tissue from
      subjects with a different grade of obesity. Adipose tissue samples were collected
      from subjects with a different degree of obesity determined by their body mass
      index (BMI) as: Overweight subjects (BMI >= 25 and <30), obese class 1/2 subjects
      (BMI >= 30 and <40) and obese class 3 subjects (BMI >= 40). C3 DNA methylation
      was measured for 7 CpGs by pyrosequencition using the Pyromark technology
      (Qiagen, Madrid Spain). C3 messenger RNA (mRNA) levels were analyzed by pre
      designed Taqman assays (Applied biosystems, Foster City, CA, USA) and ASP/C3a was
      measured using a ELISA kit. The data were analyzed using the statistic package
      SPSS. C3 DNA methylation levels were lower in the morbid obese group.
      Accordingly, C3 methylation correlated negatively with BMI and leptin. However,
      C3 mRNA levels were more associated with insulin resistance, and positive
      correlations with insulin, glucose and homeostasis model assessment-estimated
      insulin resistance (HOMA-IR) existed. ASP correlated negatively with high density
      lipoprotein (HDL) cholesterol. C3 methylation levels were associated to adiposity
      variables, such as BMI and leptin, while the C3 mRNA levels were associated to
      glucose metabolism.

PMID- 30104554
TI  - Medication-Related Burden among Patients with Chronic Disease Conditions:
      Perspectives of Patients Attending Non-Communicable Disease Clinics in a Primary
      Healthcare Setting in Qatar.
AB  - This study aimed to assess perceived medication-related burden among patients
      with multiple non-communicable diseases (NCDs) and to investigate the association
      between perceived burden and adherence to medication therapy. Using a cross
      sectional study in three primary care clinics in Qatar, medication-related burden
      was measured using the Living with Medicines Questionnaire (LMQ) among adults
      with diabetes, with or without other comorbidities. Adherence was measured using
      the Adherence to Refills and Medications Scale (ARMS). Two hundred and ninety
      three eligible patients participated in the study. The majority of them reported
      experiencing minimal (66.8%) to moderate (24.1%) medication-related burden. There
      was a significant positive correlation between the scores of the LMQ (medication
      related burden) and ARMS (medication adherence), rs (253) = 0.317, p < 0.0005.

PMID- 30104555
TI  - A Bayesian Approach to Real-Time Monitoring and Forecasting of Chinese Foodborne
      Diseases.
AB  - Foodborne diseases have a big impact on public health and are often
      underreported. This is because a lot of patients delay treatment when they suffer
      from foodborne diseases. In Hunan Province (China), a total of 21,226 confirmed
      foodborne disease cases were reported from 1 March 2015 to 28 February 2016 by
      the Foodborne Surveillance Database (FSD) of the China National Centre for Food
      Safety Risk Assessment (CFSA). The purpose of this study was to make use of the
      daily number of visiting patients to forecast the daily true number of patients.
      Our main contribution is that we take the reporting delays into consideration and
      propose a Bayesian hierarchical model for this forecast problem. The data shows
      that there were 21,226 confirmed cases reported among 21,866 visiting patients, a
      proportion as high as 97%. Given this observation, the Bayesian hierarchical
      model was established to predict the daily true number of patients using the
      number of visiting patients. We propose several scoring rules to assess the
      performance of different nowcasting procedures. We conclude that Bayesian
      nowcasting with consideration of right truncation of the reporting delays has a
      good performance for short-term forecasting, and could effectively predict the
      epidemic trends of foodborne diseases. Meanwhile, this approach could provide a
      methodological basis for future foodborne disease monitoring and control
      strategies, which are crucial for public health.

PMID- 30104557
TI  - RFID Technology for Management and Tracking: e-Health Applications.
AB  - Radio frequency identification (RFID) has become a key technology in the
      logistics and management industry, thanks to distinctive features such as the low
      cost of RFID tags, and the easiness of the RFID tags' deployment and integration
      within the items to be tracked. In consequence, RFID plays a fundamental role in
      the so-called digital factory or 4.0 Industry, aiming to increase the level of
      automatization of industrial processes. In addition, RFID has also been found to
      be of great help in improving the tracking of patients, medicines, and medical
      assets in hospitals, where the digitalization of these operations improves their
      efficiency and safety. This contribution reviews the state-of-the-art of RFID for
      e-Health applications, describing the contributions to improve medical services
      and discussing the limitations. In particular, it has been found that a lot of
      effort has been put into software development, but in most of the cases a
      detailed study of the physical layer (that is, the characterization of the RFID
      signals within the area where the system is deployed) is not properly conducted.
      This contribution describes a basic RFID system for tracking and managing assets
      in hospitals, aiming to provide additional details about implementation aspects
      that must be considered to ensure proper functionality of the system. Although
      the scope of the RFID system described in this contribution is restricted to a
      small area of the hospital, the architecture is fully scalable to cover the needs
      of the different medical services in the hospital. Ultra high-frequency (UHF)
      RFID technology is selected over the most extended near-field communication (NFC)
      and high-frequency (HF) RFID technology to minimize hardware infrastructure. In
      particular, UHF RFID also makes the coverage/reading area conformation easier by
      using different kinds of antennas. Information is stored in a database, which is
      accessed from end-user mobile devices (tablets, smartphones) where the position
      and status of the assets to be tracked are displayed.

PMID- 30104558
TI  - Asbestos Exposure and the Mesothelioma Incidence in Poland.
AB  - : Asbestos is carcinogenic to humans; the exposure to asbestos causes a wide
      range of diseases. AIM: Malignant mesothelioma (MM) is unique for asbestos
      exposure. METHODS: Based on the physical inventory of asbestos-cement roofing,
      the social-economic situation of communes, the proximity of asbestos
      manufacturing plants, the land use data referring to the surface of the built-up
      area, and the historical data on the annexations, the amount of asbestos
      containing products in use was estimated by computing best Random Forest models.
      Per capita asbestos use is an indicator to compare the state of asbestos use
      among countries. MM cases in the local administrative units (provinces) were
      tested by the application of Moran's I and Getis and Ord statistic. RESULTS: The
      total amount of asbestos roofing in Poland was estimated at 738,068,000 m2 (8.2
      million tons). In total there were 28 plants in Poland located in 11 provinces
      throughout the country. The amount of asbestos-cement roofing in use is
      correlated primarily with the measurements of asbestos concentration fibers (rs =
      0.597). MM raw morbidity rate was calculated, stratified by province, and
      classified into five groups with respect to incidence. Hotspots of MM cases are
      in the southern part of Poland. CONCLUSIONS: MM cases are concentrated in the
      same geographical areas, which may indicate an increasing impact of environmental
      exposure. The results of the local and global autocorrelation clearly indicate a
      statistically significant relationship between incidences of MM in provinces.
      Poland and other Eastern European countries are among countries with low MM
      incidence rate. Detailed investigation is desirable since the current MM
      morbidity rate in Poland seems to be underestimated.

PMID- 30104556
TI  - Overview of Biological, Epidemiological, and Clinical Evidence of Radiation
      Hormesis.
AB  - The effects of low-dose radiation are being increasingly investigated in
      biological, epidemiological, and clinical studies. Many recent studies have
      indicated the beneficial effects of low doses of radiation, whereas some studies
      have suggested harmful effects even at low doses. This review article introduces
      various studies reporting both the beneficial and harmful effects of low-dose
      radiation, with a critique on the extent to which respective studies are
      reliable. Epidemiological studies are inherently associated with large biases,
      and it should be evaluated whether the observed differences are due to radiation
      or other confounding factors. On the other hand, well-controlled laboratory
      studies may be more appropriate to evaluate the effects of low-dose radiation.
      Since the number of such laboratory studies is steadily increasing, it will be
      concluded in the near future whether low-dose radiation is harmful or beneficial
      and whether the linear-no-threshold (LNT) theory is appropriate. Many recent
      biological studies have suggested the induction of biopositive responses such as
      increases in immunity and antioxidants by low-dose radiation. Based on recent as
      well as classical studies, the LNT theory may be out of date, and low-dose
      radiation may have beneficial effects depending on the conditions; otherwise, it
      may have no effects.

PMID- 30104559
TI  - Chronic Gastritis Due to Helicobacter Pylori Associated with Increased Serum
      Levels of CA54/61: A Report of Three Cases.
AB  - BACKGROUND The bacterial pathogen Helicobacter pylori (H. pylori) can cause
      chronic gastritis. CA54/61 is a serum tumor marker that has been shown to be
      positive in the several types of human malignancy. However, the association of
      between chronic gastritis due to H. pylori and elevated serum levels of CA54/61
      has not been previously reported. This report is of three cases of increased
      serum levels of CA54/61 associated with H. pylori chronic gastritis. CASE REPORT
      Case 1 was a 44-year-old Japanese woman with a serum CA54/61 level of 138 U/ml
      (normal level: 12 U/ml). Following treatment and eradication of H. pylori the
      serum CA54/61 level decreased to 14 U/ml. Case 2 was a 73-year-old Japanese man
      with a serum level of less than 2 U/ml before completion of successful
      eradication therapy of H. pylori with a small peak of 30 U/ml after therapy. Case
      3 was a 54-year-old Japanese man who maintained a serum CA54/61 level of
      approximately 20 U/ml before and until 603 days after eradication therapy. None
      of the three patients had malignancy, which is usually suggested by this serum
      marker. CONCLUSIONS These three case reports suggest the possibility of an
      association between chronic gastritis involving H. pylori infection and an
      elevated serum level of CA54/61. It is possible that the inflammatory gastric
      mucosal cells supply CA54/61 to the bloodstream. However, further studies are
      required to confirm the association between serum levels of CA54/61 and H. pylori
      chronic gastritis and the underlying mechanisms of this association.

PMID- 30104561
TI  - Gallbladder Pathologies in Kidney Transplant Recipients: Single-Center Experience
      and a Review of the Literature.
AB  - BACKGROUND In patients with end-stage renal disease, cholelithiasis is observed
      with an increased frequency. In transplant recipients, symptoms might be
      obscured, which may delay the diagnosis and lead to complications. The aim of our
      study was to evaluate the frequency of gallbladder pathologies in kidney
      transplant recipients (KTRs) in the Caucasian population, and to discuss the
      potential benefits of prophylactic cholecystectomy before kidney transplantation
      (KT). MATERIAL AND METHODS Data from 434 patients who underwent KT was analyzed.
      Demographic data along with gallbladder status were collected from the pre
      transplantation charts. We compared our results to data from the general Polish
      population. RESULTS In our analyzed group of KTRs, there were 284 men and 150
      women. Complete data, including abdominal ultrasound description, were available
      in 412 cases. In this group, 36 patients (8.74%) underwent cholecystectomy before
      KT. Other gallbladder pathologies (gallstones and polyps) were found in 41
      patients (9.95%) at pre-transplantation evaluation. The incidence of gallbladder
      pathologies in KTRs, being mostly cholelithiasis, was higher than in the general
      Polish population. CONCLUSIONS In specific age subgroups of KTRs, the frequency
      of gallbladder pathologies was higher than in the general population.
      Prophylactic cholecystectomy may potentially offer benefits in these subgroups of
      patients.

PMID- 30104560
TI  - Short Implants and Conventional Implants in The Residual Maxillary Alveolar
      Ridge: A 36-Month Follow-Up Observation.
AB  - BACKGROUND Short dental implants are considered an alternative method of
      treatment to the maxillary sinus elevation and bone augmentation procedure at the
      sites of a reduced alveolar ridge height. The aim of the study was to determine
      the most effective therapeutic approach for a single tooth replacement in a
      reduced maxillary alveolar crest. MATERIAL AND METHODS We enrolled 30 partially
      edentulous patients having a residual crestal height of 6 mm and a minimal width
      of the alveolar ridge of 6-7 mm: 15 patients received regular dental implants
      (OsseoSpeedTM L11 O4 mm and L13 O4 mm) and the implantation was preceded by the
      sinus lift procedure from a lateral window approach with the application of a
      xenogeneic bone graft, whereas the remaining 15 patients received short implants
      (OsseoSpeedTM L6 mm O4 mm) without the sinus lift and augmentation procedure. All
      implants were loaded with single non-splinted crowns. Radiological examination
      (CBCT, RVG) was performed before the surgery and after 36 months. Primary and
      secondary stabilization with Osstell ISQ(r) and Periotest(r) were assessed.
      RESULTS Good results in primary and secondary stability were achieved in both
      systems. The marginal bone level (MBL) loss was low (0.22+/-0.46 mm and 0.34+/
      0.24 mm, for short and conventional implants, respectively). No significant
      difference in MBL between groups was found. CONCLUSIONS Short implants can be
      successfully used to support single crowns in the lateral part of the maxilla.

PMID- 30104562
TI  - [Neuroticism and suicidal thoughts: a meta-analytic study].
AB  - BACKGROUND: There are conflicting results on the relationship between neuroticism
      and suicidal ideation in community population. The objectives of this study were
      to estimate the magnitude and direction of the association between neuroticism
      and suicide ideation, and to analyze the influence of moderator variables on the
      effect size. METHODS: A systematic review and a meta-analysis were carried out.
      The search for studies was conducted in PubMed/MEDLINE, IME, Lilacs, CINAHL, and
      EMBASE, until January 2015. A manual search was also carried out and main
      researchers were contacted. The inclusion criteria were: (a) studies of the
      association between neuroticism and suicidal ideation; (b) observational and
      descriptive studies; (c) studies carried out with community population over 18
      years; (d) in any geographic region; and (e) written in English, Spanish, French,
      Portuguese or Italian. The random-effects model was applied to obtain the mean
      effect size and to explore moderators. RESULTS: Thirteen articles focused on the
      association between neuroticism and suicide ideation were included in the meta
      analysis. The mean effect size was r+ = 0.446 (IC 95%: 0.266-0.595). Publication
      bias was discarded as a threat against the validity of the results. A predictive
      model was stablished with two moderator variables: gender and type of self-report
      to measure neuroticism. CONCLUSIONS: Neuroticism can be considered as a risk
      factor for suicide ideation. This result is important to prevent both suicidal
      ideation and suicide behavior.

PMID- 30104563
TI  - Single-molecule detection with a millimetre-sized transistor.
AB  - Label-free single-molecule detection has been achieved so far by funnelling a
      large number of ligands into a sequence of single-binding events with few
      recognition elements host on nanometric transducers. Such approaches are
      inherently unable to sense a cue in a bulk milieu. Conceptualizing cells' ability
      to sense at the physical limit by means of highly-packed recognition elements, a
      millimetric sized field-effect-transistor is used to detect a single molecule. To
      this end, the gate is bio-functionalized with a self-assembled-monolayer of 1012
      capturing anti-Immunoglobulin-G and is endowed with a hydrogen-bonding network
      enabling cooperative interactions. The selective and label-free single molecule
      IgG detection is strikingly demonstrated in diluted saliva while 15 IgGs are
      assayed in whole serum. The suggested sensing mechanism, triggered by the
      affinity binding event, involves a work-function change that is assumed to
      propagate in the gating-field through the electrostatic hydrogen-bonding network.
      The proposed immunoassay platform is general and can revolutionize the current
      approach to protein detection.

PMID- 30104565
TI  - Apparent bias toward long gene misregulation in MeCP2 syndromes disappears after
      controlling for baseline variations.
AB  - Recent studies have suggested that genes longer than 100 kb are more likely to be
      misregulated in neurological diseases associated with synaptic dysfunction, such
      as autism and Rett syndrome. These length-dependent transcriptional changes are
      modest in MeCP2-mutant samples, but, given the low sensitivity of high-throughput
      transcriptome profiling technology, here we re-evaluate the statistical
      significance of these results. We find that the apparent length-dependent trends
      previously observed in MeCP2 microarray and RNA-sequencing datasets disappear
      after estimating baseline variability from randomized control samples. This is
      particularly true for genes with low fold changes. We find no bias with
      NanoString technology, so this long gene bias seems to be particular to
      polymerase chain reaction amplification-based platforms. In contrast, authentic
      long gene effects, such as those caused by topoisomerase inhibition, can be
      detected even after adjustment for baseline variability. We conclude that
      accurate characterization of length-dependent (or other) trends requires
      establishing a baseline from randomized control samples.

PMID- 30104564
TI  - Quantum confined peptide assemblies with tunable visible to near-infrared
      spectral range.
AB  - Quantum confined materials have been extensively studied for photoluminescent
      applications. Due to intrinsic limitations of low biocompatibility and
      challenging modulation, the utilization of conventional inorganic quantum
      confined photoluminescent materials in bio-imaging and bio-machine interface
      faces critical restrictions. Here, we present aromatic cyclo-dipeptides that
      dimerize into quantum dots, which serve as building blocks to further self
      assemble into quantum confined supramolecular structures with diverse
      morphologies and photoluminescence properties. Especially, the emission can be
      tuned from the visible region to the near-infrared region (420 nm to 820 nm) by
      modulating the self-assembly process. Moreover, no obvious cytotoxic effect is
      observed for these nanostructures, and their utilization for in vivo imaging and
      as phosphors for light-emitting diodes is demonstrated. The data reveal that the
      morphologies and optical properties of the aromatic cyclo-dipeptide self
      assemblies can be tuned, making them potential candidates for supramolecular
      quantum confined materials providing biocompatible alternatives for broad
      biomedical and opto-electric applications.

PMID- 30104566
TI  - Visual and modular detection of pathogen nucleic acids with enzyme-DNA molecular
      complexes.
AB  - Rapid, visual detection of pathogen nucleic acids has broad applications in
      infection management. Here we present a modular detection platform, termed enzyme
      assisted nanocomplexes for visual identification of nucleic acids (enVision). The
      system consists of an integrated circuit of enzyme-DNA nanostructures, which
      function as independent recognition and signaling elements, for direct and
      versatile detection of pathogen nucleic acids from infected cells. The built-in
      enzymatic cascades produce a rapid color readout for the naked eye; the assay is
      thus fast (<2 h), sensitive (<10 amol), and readily quantified with smartphones.
      When implemented on a configurable microfluidic platform, the technology
      demonstrates superior programmability to perform versatile computations, for
      detecting diverse pathogen targets and their virus-host genome integration loci.
      We further design the enVision platform for molecular-typing of infections in
      patient endocervical samples. The technology not only improves the clinical inter
      subtype differentiation, but also expands the intra-subtype coverage to identify
      previously undetectable infections.

PMID- 30104568
TI  - Effect of dual task on gait asymmetry in patients after anterior cruciate
      ligament reconstruction.
AB  - Individuals who received anterior cruciate ligament (ACL) reconstruction
      surgeries demonstrated lower extremity movement asymmetries. The purpose of this
      study was to determine if psychological impairment was a contributor to lower
      extremity movement asymmetries in walking for individuals who received ACL
      reconstruction surgeries. Three-dimensional videographic and force plate data
      were collected for 25 males after unilateral ACL reconstruction performing
      walking without (single-task condition) and with the concurrent cognitive task
      (dual-task condition). Both uninjured and injured legs had significantly smaller
      peak knee flexion angle and peak knee extension moment during loading response
      and mid-stance phases in dual-task condition compared to single task condition (P
      <= 0.012). Walking condition and leg had significant interaction effects on peak
      hip adduction angle during mid-stance phase (P = 0.042) and peak hip abduction
      moment during loading response phase (P = 0.048). The inter-leg difference of
      peak hip adduction angle during mid-stance (P = 0.038) and terminal stance (P =
      0.036) phases, and peak hip abduction moment during loading response phase (P =
      0.024) were significantly decreased in dual-task condition compared to single
      task condition. Psychological factors have significant effects on post-operative
      movements of both injured and uninjured knees of individuals who received ACL
      reconstruction surgery. Although physical factors may be primary contributors to
      the post-operative lower extremity movement asymmetries, psychological factors
      also contribute to the post-operative hip movement asymmetries.

PMID- 30104569
TI  - A multi-state model of chemoresistance to characterize phenotypic dynamics in
      breast cancer.
AB  - The development of resistance to chemotherapy is a major cause of treatment
      failure in breast cancer. While mathematical models describing the dynamics of
      resistant cancer cell subpopulations have been proposed, experimental validation
      has been difficult due to the complex nature of resistance that limits the
      ability of a single phenotypic marker to sufficiently identify the drug resistant
      subpopulations. We address this problem with a coupled experimental/modeling
      approach to reveal the composition of drug resistant subpopulations changing in
      time following drug exposure. We calibrate time-resolved drug sensitivity assays
      to three mathematical models to interrogate the models' ability to capture drug
      response dynamics. The Akaike information criterion was employed to evaluate the
      three models, and it identified a multi-state model incorporating the role of
      population heterogeneity and cellular plasticity as the optimal model. To
      validate the model's ability to identify subpopulation composition, we mixed
      different proportions of wild-type MCF-7 and MCF-7/ADR resistant cells and
      evaluated the corresponding model output. Our blinded two-state model was able to
      estimate the proportions of cell types with an R-squared value of 0.857. To the
      best of our knowledge, this is the first work to combine experimental time
      resolved drug sensitivity data with a mathematical model of resistance
      development.

PMID- 30104570
TI  - Fragile aspects of topological transition in lossy and parity-time symmetric
      quantum walks.
AB  - Quantum walks often provide telling insights about the structure of the system on
      which they are performed. In [Formula: see text]-symmetric and lossy dimer
      lattices, the topological properties of the band structure manifest themselves in
      the quantization of the mean displacement of such a walker. We investigate the
      fragile aspects of a topological transition in these two dimer models. We find
      that the transition is sensitive to the initial state of the walker on the Bloch
      sphere, and the resultant mean displacement has a robust topological component
      and a quasiclassical component. In [Formula: see text] symmetric dimer lattices,
      we also show that the transition is smeared by nonlinear effects that become
      important in the [Formula: see text]-symmetry broken region. By carrying out
      consistency checks via analytical calculations, tight-binding results, and beam
      propagation-method simulations, we show that our predictions are easily testable
      in today's experimental systems.

PMID- 30104571
TI  - Length-scale dependency of biomimetic hard-soft composites.
AB  - Biomimetic composites are usually made by combining hard and soft phases using,
      for example, multi-material additive manufacturing (AM). Like other fabrication
      methods, AM techniques are limited by the resolution of the device, hence,
      setting a minimum length scale. The effects of this length scale on the
      performance of hard-soft composites are not well understood. Here, we studied how
      this length scale affects the fracture toughness behavior of single-edge notched
      specimens made using random, semi-random, and ordered arrangements of the hard
      and soft phases with five different ratios of hard to soft phases. Increase in
      the length scale (40 to 960 MUm) was found to cause a four-fold drop in the
      fracture toughness. The effects of the length scale were also modulated by the
      arrangement and volumetric ratio of both phases. A decreased size of the crack
      tip plastic zone, a crack path going through the soft phase, and highly strained
      areas far from the crack tip were the main mechanisms explaining the drop of the
      fracture toughness with the length scale.

PMID- 30104572
TI  - Determining Relative Dynamic Stability of Cell States Using Boolean Network
      Model.
AB  - Cell state transition is at the core of biological processes in metazoan, which
      includes cell differentiation, epithelial-to-mesenchymal transition (EMT) and
      cell reprogramming. In these cases, it is important to understand the molecular
      mechanism of cellular stability and how the transitions happen between different
      cell states, which is controlled by a gene regulatory network (GRN) hard-wired in
      the genome. Here we use Boolean modeling of GRN to study the cell state
      transition of EMT and systematically compare four available methods to calculate
      the cellular stability of three cell states in EMT in both normal and genetically
      mutated cases. The results produced from four methods generally agree but do not
      totally agree with each other. We show that distribution of one-degree
      neighborhood of cell states, which are the nearest states by Hamming distance,
      causes the difference among the methods. From that, we propose a new method based
      on one-degree neighborhood, which is the simplest one and agrees with other
      methods to estimate the cellular stability in all scenarios of our EMT model.
      This new method will help the researchers in the field of cell differentiation
      and cell reprogramming to calculate cellular stability using Boolean model, and
      then rationally design their experimental protocols to manipulate the cell state
      transition.

PMID- 30104573
TI  - Detection of opsonizing antibodies directed against a recently circulating
      Bordetella pertussis strain in paired plasma samples from symptomatic and
      recovered pertussis patients.
AB  - Correlates of protection (CoPs) against the highly contagious respiratory disease
      whooping cough, caused by Bordetella pertussis, remain elusive. Characterizing
      the antibody response to this pathogen is essential towards identifying potential
      CoPs. Here, we evaluate levels, avidity and functionality of B. pertussis
      specific-antibodies from paired plasma samples derived from symptomatic and
      recovered pertussis patients, as well as controls. Natural infection is expected
      to induce protective immunity. IgG levels and avidity to nine B. pertussis
      antigens were determined using a novel multiplex panel. Furthermore,
      opsonophagocytosis of a B. pertussis clinical isolate by neutrophils was
      measured. Findings indicate that following infection, B. pertussis-specific
      antibody levels of (ex-) pertussis patients waned, while the avidity of
      antibodies directed against the majority of studied antigens increased.
      Opsonophagocytosis indices decreased upon recovery, but remained higher than
      controls. Random forest analysis of all the data revealed that 28% of the
      opsonophagocytosis index variances could be explained by filamentous
      hemagglutinin- followed by pertussis toxin-specific antibodies. We propose to
      further explore which other B. pertussis-specific antibodies can better predict
      opsonophagocytosis. Moreover, other B. pertussis-specific antibody functions as
      well as the possible integration of these functions in combination with other
      immune cell properties should be evaluated towards the identification of CoPs
      against pertussis.

PMID- 30104567
TI  - Identification of susceptibility pathways for the role of chromosome 15q25.1 in
      modifying lung cancer risk.
AB  - Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as
      a leading susceptibility region for lung cancer. However, the pathogenic
      pathways, through which susceptibility SNPs within chromosome 15q25.1 affects
      lung cancer risk, have not been explored. We analyzed three cohorts with GWAS
      data consisting 42,901 individuals and lung expression quantitative trait loci
      (eQTL) data on 409 individuals to identify and validate the underlying pathways
      and to investigate the combined effect of genes from the identified
      susceptibility pathways. The KEGG neuroactive ligand receptor interaction
      pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and
      replicated to be significantly associated with lung cancer risk, with P values
      less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis
      results showed that the neuroactive ligand receptor interaction pathway and gated
      channel activity were involved in lung cancer risk. These pathways provide
      important insights for the etiology of lung cancer.

PMID- 30104574
TI  - Identification and functional study of a mild allele of SlDELLA gene conferring
      the potential for improved yield in tomato.
AB  - Parthenocarpy, or pollination-independent fruit set, is an attractive trait for
      fruit production and can be induced by increased responses to the phytohormone
      gibberellin (GA), which regulates diverse aspects of plant development. GA
      signaling in plants is negatively regulated by DELLA proteins. A loss-of-function
      mutant of tomato DELLA (SlDELLA), procera (pro) thus exhibits enhanced GA
      response phenotypes including parthenocarpy, although the pro mutation also
      confers some disadvantages for practical breeding. This study identified a new
      milder hypomorphic allele of SlDELLA, procera-2 (pro-2), which showed weaker GA
      response phenotypes than pro. The pro-2 mutant contains a single nucleotide
      substitution, corresponding to a single amino acid substitution in the SAW
      subdomain of the SlDELLA. Accumulation of the mutated SlDELLA transcripts in wild
      type (WT) resulted in parthenocarpy, while introduction of intact SlDELLA into
      pro-2 rescued mutant phenotypes. Yeast two-hybrid assays revealed that SlDELLA
      interacted with three tomato homologues of GID1 GA receptors with increasing
      affinity upon GA treatment, while their interactions were reduced by the pro and
      pro-2 mutations. Both pro and pro-2 mutants produced higher fruit yields under
      high temperature conditions, which were resulted from higher fruit set
      efficiency, demonstrating the potential for genetic parthenocarpy to improve
      yield under adverse environmental conditions.

PMID- 30104577
TI  - Extrachromosomal circular elements targeted by CRISPR-Cas in Dehalococcoides
      mccartyi are linked to mobilization of reductive dehalogenase genes.
AB  - Dehalococcoides mccartyi are obligate organohalide-respiring bacteria that play
      an important detoxifying role in the environment. They have small genomes (~1.4
      Mb) with a core region interrupted by two high plasticity regions (HPRs)
      containing dozens of genes encoding reductive dehalogenases involved in
      organohalide respiration. The genomes of eight new strains of D. mccartyi were
      closed from metagenomic data from a related set of enrichment cultures, bringing
      the total number of genomes to 24. Two of the newly sequenced strains and three
      previously sequenced strains contain CRISPR-Cas systems. These D. mccartyi CRISPR
      Cas systems were found to primarily target prophages and genomic islands. The
      genomic islands were identified either as integrated into D. mccartyi genomes or
      as circular extrachromosomal elements. We observed active circularization of the
      integrated genomic island containing vcrABC operon encoding the dehalogenase
      (VcrA) responsible for the transformation of vinyl chloride to non-toxic ethene.
      We interrogated archived DNA from established enrichment cultures and found that
      the CRISPR array acquired three new spacers in 11 years. These data provide a
      glimpse into dynamic processes operating on the genomes distinct to D. mccartyi
      strains found in enrichment cultures and provide the first insights into possible
      mechanisms of lateral DNA exchange in D. mccartyi.

PMID- 30104576
TI  - Iterative and discrete reconstruction in the evaluation of the rabbit model of
      osteoarthritis.
AB  - Micro-computed tomography (uCT) is a standard method for bone morphometric
      evaluation. However, the scan time can be long and the radiation dose during the
      scan may have adverse effects on test subjects, therefore both of them should be
      minimized. This could be achieved by applying iterative reconstruction (IR) on
      sparse projection data, as IR is capable of producing reconstructions of
      sufficient image quality with less projection data than the traditional algorithm
      requires. In this work, the performance of three IR algorithms was assessed for
      quantitative bone imaging from low-resolution data in the evaluation of the
      rabbit model of osteoarthritis. Subchondral bone images were reconstructed with a
      conjugate gradient least squares algorithm, a total variation regularization
      scheme, and a discrete algebraic reconstruction technique to obtain quantitative
      bone morphometry, and the results obtained in this manner were compared with
      those obtained from the reference reconstruction. Our approaches were sufficient
      to identify changes in bone structure in early osteoarthritis, and these changes
      were preserved even when minimal data were provided for the reconstruction. Thus,
      our results suggest that IR algorithms give reliable performance with sparse
      projection data, thereby recommending them for use in uCT studies where time and
      radiation exposure are preferably minimized.

PMID- 30104575
TI  - Cancer stem cells as targets for DC-based immunotherapy of colorectal cancer.
AB  - The therapy of colorectal cancer (CRC) patients is often unsuccessful because of
      the presence of cancer stem cells (CSCs) resistant to conventional approaches.
      Dendritic cells (DC)-based protocols are believed to effectively supplement CRC
      therapy. Our study was aimed to assess how the number and properties of CSCs
      isolated from tumor tissue of CRC patients will affect the biological
      characteristics of in vitro modified DCs. Similar procedures were conducted with
      the using of CRC HCT116 and HT29 cell lines. We found that the detailed
      configuration of CSC-like markers significantly influenced the maturation and
      activation of DCs after stimulation with cancer cells lysates or culture
      supernatants. This basic stimulatory effect was enhanced by LPS that is normally
      present in CRC CSCs niche. The increased number of CD29+ and CD44+ CSCs presented
      the opposite impact on treated DCs as showed by many significant correlations.
      The CD133+ CSCs seemed to impair the functions of DCs. The more CD133+ CSCs in
      tumor sample the lower number of activated DCs evidenced after stimulation.
      Moreover, our results showed superiority of the spherical culture model over the
      adherent one since spherical HCT116 and HT29 cells presented similar influence on
      DCs properties as CRC patients cancer cells. We concluded that the DCs features
      may depend directly on the properties of CSCs affected by progression status of
      tumor.

PMID- 30104578
TI  - Distribution of posterior corneal astigmatism and aberration before cataract
      surgery in Chinese patients.
AB  - PURPOSE: To study the prevalence of posterior corneal astigmatism (PCA) and
      aberration in Chinese eyes before cataract surgery. METHODS: A cross-sectional
      study was conducted in Eye and ENT Hospital of Fudan University, Shanghai. In
      all, we enrolled 1976 eligible eyes of 1976 cataract patients. The astigmatism
      and aberrations of anterior and posterior cornea were measured by the rotating
      Scheimpflug System (Pentacam HR, Oculus). Cataract was diagnosed using slit-lamp
      examination. RESULTS: The mean age of patients was 61.82 +/- 13.67 years old.
      Mean PCA was 0.28 +/- 0.16 (range 0-1.0) D and 87.04% eyes had PCA values <0.5 D.
      WTR astigmatism predominated the anterior cornea astigmatism (43.1%), while ATR
      astigmatism predominated posterior (85.4%) and total corneal astigmatism (47.2%).
      We found a shift tendency of WTR to ATR with aging in anterior corneal
      astigmatism, while PCA remains ATR. A positive correlation between the magnitude
      of anterior and posterior corneal astigmatism (r2 = 0.089, P < 0.001) was found,
      especially in WTR anterior cornea astigmatism eyes (r2 = 0.298, P < 0.001).
      Compared with total corneal astigmatism, anterior corneal measurements
      overestimated WTR astigmatism by a mean of 0.24 +/- 0.13 (D), and underestimated
      ATR astigmatism and oblique astigmatism in most eyes. Furthermore, anterior
      corneal aberrations measurements overestimated the total corneal aberration in
      most eyes. CONCLUSIONS: About 12.96% of eyes had PCA >=0.5 D. The posterior
      surface remained ATR astigmatism in most cases with aging. Neglecting the
      posterior cornea would result in overestimation in WTR anterior corneal eyes and
      underestimation in ATR and oblique anterior corneal eyes. Also, the posterior
      corneal aberration was also essential in clinics.

PMID- 30104579
TI  - Floral evolution by simplification in Monanthotaxis (Annonaceae) and hypotheses
      for pollination system shifts.
AB  - Simplification by reduction has occurred many times independently in the floral
      evolution of angiosperms. These reductions have often been attributed to changes
      in reproductive biology. In the angiosperm plant family Annonaceae, most species
      have flowers with six petals, and many stamens and carpels. In the genus
      Monanthotaxis several deviations from this pattern have been observed, including
      flowers that contain three petals and three stamens only. New DNA sequences were
      generated for 42 specimens of Monanthotaxis. Five chloroplast markers and two
      nuclear markers for 72 out of 94 species of Monanthotaxis were used to
      reconstruct a phylogeny of the genus, which revealed several well-supported,
      morphologically distinct clades. The evolution of four quantitative and two
      qualitative floral characters was mapped onto this phylogeny, demonstrating a
      reduction in flower size and number of flower parts in Monanthotaxis. A large
      variation in stamen forms and numbers, strong correlations between petal size,
      stamen and carpel number, combined with a non-gradual mode of evolution and the
      sympatric co-occurrence of Monanthotaxis species from different clades suggest
      that the high diversity in the African rainforest of this genus is caused by
      switches in pollination systems.

PMID- 30104580
TI  - High Sensitivity and Selectivity of AsP Sensor in Detecting SF6 Decomposition
      Gases.
AB  - The sensing properties of monolayer arsenic phosphorus (AsP) for the adsorption
      of SF6, H2O, O2, and SF6 decomposition gases (SO2 and H2S) are theoretically
      investigated by the first-principle calculations. We calculate the adsorption
      energy, equilibrium distance, Mulliken charge transfer, and electron localization
      function (ELF) to explore whether AsP is suitable for detecting SF6 decomposition
      gases. By comparing the adsorption performance of SF6, H2O, O2, and H2S gases, we
      have revealed that the SO2 gas molecules could form stable chemisorption with AsP
      monolayer. The results demonstrate that AsP is highly sensitive and selective to
      SO2 gas molecules with robust adsorption energy and apparent charge transfer.
      Furthermore, the current-voltage (I-V) curves reveal that only the adsorption of
      SO2 can largely modify the resistance of AsP. Our results show that gas sensors
      based on AsP monolayer could be better than that of black phosphorene (BP) to
      diagnose the state of online gas-insulated switchgear (GIS).

PMID- 30104582
TI  - STING'ing Zika virus in neurons.

PMID- 30104590
TI  - Special relativity validated by neutrinos.

PMID- 30104581
TI  - Social support rescues acute stress-induced cognitive impairments by modulating
      ERK1/2 phosphorylation in adolescent mice.
AB  - Social support can relieve stress-induced behavioural outcomes, although its
      underlying molecular mechanisms are not fully understood. Here, we evaluated
      whether social interactions can prevent the restraint stress (RS)-induced
      cognitive impairments in male adolescent mice by utilizing molecular, cellular,
      and behavioural approaches. Acute RS in adolescent ICR mice impaired the working
      memory in the Y-maze test and memory consolidation and retrieval in the novel
      object-recognition test (NORT). In addition, RS increased the extracellular
      signal-regulated kinases 1/2 phosphorylation (p-ERK1/2) in the prefrontal cortex
      (PFC) and corticosterone levels in the plasma. Interestingly, these outcomes were
      normalized by the presence of a conspecific animal (social support) during RS. RS
      also significantly upregulated the expression levels of known stress-relevant
      genes such as Egr1, Crh, and Crhr1, which were normalized by social support.
      Systemic injection of SL327 (an inhibitor of MEK1/2 that also blocks its
      downstream signal ERK1/2) prior to RS rescued the working memory impairments and
      the increased p-ERK1/2 while normalizing the expression of Egr1. Our results
      suggest that social support can alleviate the RS-induced cognitive impairments
      partly by modulating ERK1/2 phosphorylation and gene transcription in the PFC,
      and provide novel insights into the molecular mechanisms of the stress-buffering
      effects of social support.

PMID- 30104592
TI  - The spectre of smallpox lingers.

PMID- 30104593
TI  - Sex, religion and a towering treatise on anatomy.

PMID- 30104594
TI  - Top tips for building and maintaining international collaborations.

PMID- 30104595
TI  - A universal curve of apatite crystallinity for the assessment of bone integrity
      and preservation.
AB  - The reliable determination of bioapatite crystallinity is of great practical
      interest, as a proxy to the physico-chemical and microstructural properties, and
      ultimately, to the integrity of bone materials. Bioapatite crystallinity is used
      to diagnose pathologies in modern calcified tissues as well as to assess the
      preservation state of fossil bones. To date, infrared spectroscopy is one of the
      most applied techniques for bone characterisation and the derived infrared
      splitting factor (IRSF) has been widely used to practically assess bioapatite
      crystallinity. Here we thoroughly discuss and revise the use of the IRSF
      parameter and its meaning as a crystallinity indicator, based on extensive
      measurements of fresh and fossil bones, virtually covering the known range of
      crystallinity degree of bioapatite. A novel way to calculate and use the infrared
      peak width as a suitable measurement of true apatite crystallinity is proposed,
      and validated by combined measurement of the same samples through X-ray
      diffraction. The non-linear correlation between the infrared peak width and the
      derived ISRF is explained. As shown, the infrared peak width at 604 cm-1 can be
      effectively used to assess both the average crystallite size and structural
      carbonate content of bioapatite, thus establishing a universal calibration curve
      of practical use.

PMID- 30104597
TI  - Post-polymerisation functionalisation of conjugated polymer backbones and its
      application in multi-functional emissive nanoparticles.
AB  - Backbone functionalisation of conjugated polymers is crucial to their performance
      in many applications, from electronic displays to nanoparticle biosensors, yet
      there are limited approaches to introduce functionality. To address this
      challenge we have developed a method for the direct modification of the aromatic
      backbone of a conjugated polymer, post-polymerisation. This is achieved via a
      quantitative nucleophilic aromatic substitution (SNAr) reaction on a range of
      fluorinated electron-deficient comonomers. The method allows for facile tuning of
      the physical and optoelectronic properties within a batch of consistent molecular
      weight and dispersity. It also enables the introduction of multiple different
      functional groups onto the polymer backbone in a controlled manner. To
      demonstrate the versatility of this reaction, we designed and synthesised a range
      of emissive poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT)-based polymers
      for the creation of mono and multifunctional semiconducting polymer nanoparticles
      (SPNs) capable of two orthogonal bioconjugation reactions on the same surface.

PMID- 30104596
TI  - Probing high-momentum protons and neutrons in neutron-rich nuclei.
AB  - The atomic nucleus is one of the densest and most complex quantum-mechanical
      systems in nature. Nuclei account for nearly all the mass of the visible
      Universe. The properties of individual nucleons (protons and neutrons) in nuclei
      can be probed by scattering a high-energy particle from the nucleus and detecting
      this particle after it scatters, often also detecting an additional knocked-out
      proton. Analysis of electron- and proton-scattering experiments suggests that
      some nucleons in nuclei form close-proximity neutron-proton pairs1-12 with high
      nucleon momentum, greater than the nuclear Fermi momentum. However, how excess
      neutrons in neutron-rich nuclei form such close-proximity pairs remains unclear.
      Here we measure protons and, for the first time, neutrons knocked out of medium
      to-heavy nuclei by high-energy electrons and show that the fraction of high
      momentum protons increases markedly with the neutron excess in the nucleus,
      whereas the fraction of high-momentum neutrons decreases slightly. This effect is
      surprising because in the classical nuclear shell model, protons and neutrons
      obey Fermi statistics, have little correlation and mostly fill independent energy
      shells. These high-momentum nucleons in neutron-rich nuclei are important for
      understanding nuclear parton distribution functions (the partial momentum
      distribution of the constituents of the nucleon) and changes in the quark
      distributions of nucleons bound in nuclei (the EMC effect)1,13,14. They are also
      relevant for the interpretation of neutrino-oscillation measurements15 and
      understanding of neutron-rich systems such as neutron stars3,16.

PMID- 30104598
TI  - Revealing the mechanism for covalent inhibition of glycoside hydrolases by
      carbasugars at an atomic level.
AB  - Mechanism-based glycoside hydrolase inhibitors are carbohydrate analogs that
      mimic the natural substrate's structure. Their covalent bond formation with the
      glycoside hydrolase makes these compounds excellent tools for chemical biology
      and potential drug candidates. Here we report the synthesis of cyclohexene-based
      alpha-galactopyranoside mimics and the kinetic and structural characterization of
      their inhibitory activity toward an alpha-galactosidase from Thermotoga maritima
      (TmGalA). By solving the structures of several enzyme-bound species during
      mechanism-based covalent inhibition of TmGalA, we show that the Michaelis
      complexes for intact inhibitor and product have half-chair (2H3) conformations
      for the cyclohexene fragment, while the covalently linked intermediate adopts a
      flattened half-chair (2H3) conformation. Hybrid QM/MM calculations confirm the
      structural and electronic properties of the enzyme-bound species and provide
      insight into key interactions in the enzyme-active site. These insights should
      stimulate the design of mechanism-based glycoside hydrolase inhibitors with
      tailored chemical properties.

PMID- 30104599
TI  - Patient stratification in clinical glaucoma trials using the individual tear
      proteome.
AB  - Glaucoma patients are prone to concomitant ocular surface diseases; however,
      switching from preserved to preservative-free medication can often alleviate
      these symptoms. The objective of this study was to examine how the adverse
      effects and tear proteome change for glaucoma patients (n = 28) during a 12-month
      drug switch from preserved latanoprost (Xalatan) to preservative-free tafluprost
      (Taflotan). We hypothesized that patient stratification could help identify novel
      recovery patterns in both tear proteomics and clinical data. In order to
      accomplish patient stratification, we implemented sequential window acquisition
      of all theoretical mass spectrometry (SWATH-MS) as a tool for quantitative
      analysis of individual tear protein profiles. During each visit (baseline and
      four follow-up visits), the patients' tears were sampled and the state of their
      ocular surface was evaluated clinically. Altogether 785 proteins were quantified
      from each tear sample using SWATH strategy and as these protein expression levels
      were compared between baseline and 12-month follow-up, three distinct patient
      groups were identified. We evaluated how these patient groups differed in their
      protein expression levels at baseline and discovered that the patients with
      increased levels of pro-inflammatory proteins and decreased levels of protective
      proteins benefitted most from the medication switch.

PMID- 30104600
TI  - Differential interactions of bacterial lipopolysaccharides with lipid membranes:
      implications for TRPA1-mediated chemosensation.
AB  - Bacterial lipopolysaccharides (LPS) activate the TRPA1 cation channels in sensory
      neurons, leading to acute pain and inflammation in mice and to aversive behaviors
      in fruit flies. However, the precise mechanisms underlying this effect remain
      elusive. Here we assessed the hypothesis that TRPA1 is activated by mechanical
      perturbations induced upon LPS insertion in the plasma membrane. We asked whether
      the effects of different LPS on TRPA1 relate to their ability to induce
      mechanical alterations in artificial and cellular membranes. We found that LPS
      from E. coli, but not from S. minnesota, activates TRPA1. We then assessed the
      effects of these LPS on lipid membranes using dyes whose fluorescence properties
      change upon alteration of the local lipid environment. E. coli LPS was more
      effective than S. minnesota LPS in shifting Laurdan's emission spectrum towards
      lower wavelengths, increasing the fluorescence anisotropy of diphenylhexatriene
      and reducing the fluorescence intensity of merocyanine 540. These data indicate
      that E. coli LPS induces stronger changes in the local lipid environment than S.
      minnesota LPS, paralleling its distinct ability to activate TRPA1. Our findings
      indicate that LPS activate TRPA1 by producing mechanical perturbations in the
      plasma membrane and suggest that TRPA1-mediated chemosensation may result from
      primary mechanosensory mechanisms.

PMID- 30104602
TI  - Light-induced mechanical response in crosslinked liquid-crystalline polymers with
      photoswitchable glass transition temperatures.
AB  - Energy conversion of light into mechanical work is of fundamental interest in
      applications. In particular, diligent molecular design on nanoscale, in order to
      achieve efficient photomechanical effects on macroscopic scale, has become one of
      the most interesting study topics. Here, by incorporating a "photomelting"
      azobenzene monomer crosslinked into liquid crystalline (LC) networks, we generate
      photoresponsive polymer films that exhibit reversible photoswitchable glass
      transition temperatures (Tg) at room temperature (~20  degrees C) and
      photomechanical actuations under the stimulus of UV/visible light. The trans-to
      cis isomerization of azo chromophores results in a change in Tg of the
      crosslinked LC polymers. The Tg of the polymer network is higher than room
      temperature in the trans-form and lower than room temperature in the cis-form. We
      demonstrate the photoswitchable Tg contribute to the photomechanical bending and
      a new mechanism for photomechanical bending that attributes the process to an
      inhomogeneous change in Tg of the film is proposed.

PMID- 30104603
TI  - Effective soil erosion control represents a significant net carbon sequestration.
AB  - The debate over whether soil erosion is a carbon (C) sink or atmospheric CO2
      source remains highly controversial. For the first time, we report the magnitude
      of C stabilization associated with soil erosion control for an entire large river
      basin. The soil erosion of the Yellow River basin in northern China is among the
      most severe worldwide. Progressive soil conservation has been implemented by the
      Chinese government since the 1970s, including the largest ever revegetation
      programme, the Grain-for-Green Project, which began in 1999. Based on compiled
      hydrological records and organic carbon (OC) data, together with primary
      production estimates, we evaluated the sequestered OC resulting from soil
      conservation. Compared with that at baseline in 1950-1970, in which significant
      soil conservation did not occur, the fate of erosion-induced OC was substantially
      altered in the period from 2000-2015. Approximately 20.6 Tg of OC were
      effectively controlled per year by soil conservation efforts. Simultaneously, the
      decomposition of erosion-induced soil organic carbon (SOC) declined from 8 Tg C
      yr-1 to current 5.3 Tg C yr-1. The reduced C emissions (2.7 Tg C yr-1) within the
      Yellow River basin alone account for 12.7% of the mean C accumulation acquired
      via forest expansion throughout all of China previously assessed. If the
      accumulated C in restored plants and soils was included, then 9.7 Tg C yr-1 was
      reduced from the atmospheric C pool during this period, which represents a
      tremendous C-capturing benefit. Thus, the increased C storage obtained via soil
      conservation should be considered in future C inventories.

PMID- 30104601
TI  - Genes associated with anhedonia: a new analysis in a large clinical trial
      (GENDEP).
AB  - A key feature of major depressive disorder (MDD) is anhedonia, which is a
      predictor of response to antidepressant treatment. In order to shed light on its
      genetic underpinnings, we conducted a genome-wide association study (GWAS)
      followed by investigation of biological pathway enrichment using an anhedonia
      dimension for 759 patients with MDD in the GENDEP study. The GWAS identified 18
      SNPs associated at genome-wide significance with the top one being an intronic
      SNP (rs9392549) in PRPF4B (pre-mRNA processing factor 4B) located on chromosome 6
      (P = 2.07 * 10-9) while gene-set enrichment analysis returned one gene ontology
      term, axon cargo transport (GO: 0008088) with a nominally significant P value
      (1.15 * 10-5). Furthermore, our exploratory analysis yielded some interesting,
      albeit not statistically significant genetic correlation with Parkinson's Disease
      and nucleus accumbens gray matter. In addition, polygenic risk scores (PRSs)
      generated from our association analysis were found to be able to predict
      treatment efficacy of the antidepressants in this study. In conclusion, we found
      some markers significantly associated with anhedonia, and some suggestive
      findings of related pathways and biological functions, which could be further
      investigated in other studies.

PMID- 30104605
TI  - Optical emission near a high-impedance mirror.
AB  - Solid state light emitters rely on metallic contacts with a high sheet
      conductivity for effective charge injection. Unfortunately, such contacts also
      support surface plasmon polariton and lossy wave excitations that dissipate
      optical energy into the metal and limit the external quantum efficiency. Here,
      inspired by the concept of radio-frequency high-impedance surfaces and their use
      in conformal antennas we illustrate how electrodes can be nanopatterned to
      simultaneously provide a high DC electrical conductivity and high-impedance at
      optical frequencies. Such electrodes do not support SPPs across the visible
      spectrum and greatly suppress dissipative losses while facilitating a desirable
      Lambertian emission profile. We verify this concept by studying the emission
      enhancement and photoluminescence lifetime for a dye emitter layer deposited on
      the electrodes.

PMID- 30104606
TI  - Late Palaeolithic cave art and permafrost in the Southern Ural.
AB  - Shulgan-Tash (also known as Kapova) cave located on the western slope of the Ural
      Mountains (Russia) is the easternmost European cave art monument of late
      Palaeolithic age. Radiocarbon dates from cultural layers in the cave suggest an
      age of about 16.3 to 19.6 ka (cal BP), but dates directly on the paintings were
      not obtained. In order to constrain the age of this art using an independent
      method, we performed detailed 230Th-U dating of calcite flowstone underlying and
      overgrowing the paintings at 22 sites in three halls of the cave. The youngest
      age for the underlying calcite (i.e., the maximum age of the cave art) is 36.4 +/
      0.1 ka, and the oldest overlying calcite (constraining the minimum age of the
      cave art) is 14.5 +/- 0.04 ka. The ca. 21.9 ka-long hiatus in calcite deposition
      during which the paintings were made is attributed to regional permafrost
      conditions and sub-zero temperatures inside the cave during Marine Isotope Stage
      (MIS) 2. This is supported by samples of cryogenic cave calcite, which document
      seven episodes of freezing and thawing of permafrost associated with stadials and
      interstadials of MIS 3, respectively.

PMID- 30104607
TI  - Identification and characterization of a novel beta-D-galactosidase that releases
      pyruvylated galactose.
AB  - Pyruvyl modification of oligosaccharides is widely seen in both prokaryotes and
      eukaryotes. Although the biosynthetic mechanisms of pyruvylation have been
      investigated, enzymes that metabolize and degrade pyruvylated oligosaccharides
      are not well known. Here, we searched for a pyruvylated galactose (PvGal)
      releasing enzyme by screening soil samples. We identified a Bacillus strain, as
      confirmed by the 16S ribosomal RNA gene analysis, that exhibited PvGal-ase
      activity toward p-nitrophenyl-beta-D-pyruvylated galactopyranose (pNP-beta-D
      PvGal). Draft genome sequencing of this strain, named HMA207, identified three
      candidate genes encoding potential PvGal-ases, among which only the recombinant
      protein encoded by ORF1119 exhibited PvGal-ase activity. Although ORF1119 protein
      displayed broad substrate specificity for pNP sugars, pNP-beta-D-PvGal was the
      most favorable substrate. The optimum pH for the ORF1119 PvGal-ase was determined
      as 7.5. A BLAST search suggested that ORF1119 homologs exist widely in bacteria.
      Among two homologs tested, BglC from Clostridium but not BglH from Bacillus
      showed PvGal-ase activity. Crystal structural analysis together with point
      mutation analysis revealed crucial amino acids for PvGal-ase activity. Moreover,
      ORF1119 protein catalyzed the hydrolysis of PvGal from galactomannan of
      Schizosaccharomyces pombe, suggesting that natural polysaccharides might be
      substrates of the PvGal-ase. This novel PvGal-catalyzing enzyme might be useful
      for glycoengineering projects to produce new oligosaccharide structures.

PMID- 30104604
TI  - Snake Venom Extracellular vesicles (SVEVs) reveal wide molecular and functional
      proteome diversity.
AB  - Proteins constitute almost 95% of snake venom's dry weight and are produced and
      released by venom glands in a solubilized form during a snake bite. These
      proteins are responsible for inducing several pharmacological effects aiming to
      immobilize and initiate the pre-digestion of the prey. This study shows that
      proteins can be secreted and confined in snake venom extracellular vesicles
      (SVEVs) presenting a size distribution between 50 nm and 500 nm. SVEVs isolated
      from lyophilized venoms collected from four different species of snakes
      (Agkistrodon contortrix contortrix, Crotalus atrox, Crotalus viridis and Crotalus
      cerberus oreganus) were analyzed by mass spectrometry-based proteomic, which
      allowed the identification of proteins belonging to eight main functional protein
      classes such as SVMPs, serine proteinases, PLA2, LAAO, 5'nucleotidase, C-type
      lectin, CRISP and Disintegrin. Biochemical assays indicated that SVEVs are
      functionally active, showing high metalloproteinase and fibrinogenolytic activity
      besides being cytotoxic against HUVEC cells. Overall, this study comprehensively
      depicts the protein composition of SVEVs for the first time. In addition, the
      molecular function of some of the described proteins suggests a central role for
      SVEVs in the cytotoxicity of the snake venom and sheds new light in the
      envenomation process.

PMID- 30104608
TI  - Quinolone-fused cyclic sulfonamide as a novel benign antifilarial agent.
AB  - Search of potent antifilarial drugs has been a major thrust area in tropical
      medicine research over the decades. Herein, we report 4,7-dimethyl-3,4,7,8
      tetrahydro-3lambda6-[1,2]thiazino[4,3-f]quinoline-3,3,8-trione (8l) as a new
      class of antifilarial agent which is extremely potent, with lethality against all
      the developmental stages (oocyte, microfilaria and adult) of the filarial
      parasite Setaria cervi. Molecular investigation on its mode of action revealed
      that 8l is a typical inducer of reactive oxygen species that triggers oxidative
      stress inside the filarid and further signals induction of apoptosis by
      activating both intrinsic and extrinsic pathways. Moreover, 8l is also active
      against Wolbachia, the essential endosymbiont of several human infectious
      filarids. Selective toxicity against filarial parasites and non-toxic nature in
      rat model were found as unique traits of 8l to be a future medicine. Taken en
      masse, this maiden report on a novel quinolone fused cyclic sulfonamide presents
      a promising therapeutic lead for lymphatic filariasis in future.

PMID- 30104609
TI  - Cooperativity in Plant Plasma Membrane Intrinsic Proteins (PIPs): Mechanism of
      Increased Water Transport in Maize PIP1 Channels in Hetero-tetramers.
AB  - Plant aquaporins (AQPs) play vital roles in several physiological processes.
      Plasma membrane intrinsic proteins (PIPs) belong to the subfamily of plant AQPs.
      They are further subdivided into two closely related subgroups PIP1s and PIP2s.
      While PIP2 members are efficient water channels, PIP1s from some plant species
      have been shown to be functionally inactive. Aquaporins form tetramers under
      physiological conditions. PIP2s can enhance the water transport of PIP1s when
      they form hetero-tetramers. However, the role of monomer-monomer interface and
      the significance of specific residues in enhancing the water permeation of PIP1s
      have not been investigated at atomic level. We have performed all-atom molecular
      dynamics (MD) simulations of homo-tetramers and four different hetero-tetramers
      containing ZmPIP1;2 and ZmPIP2;5 from Zea mays. ZmPIP1;2 in a tetramer assembly
      will have two interfaces, one formed by transmembrane segments TM4 and TM5 and
      the other formed by TM1 and TM2. We have analyzed channel radius profiles, water
      transport and potential of mean force profiles of ZmPIP1;2 monomers. Results of
      MD simulations clearly revealed the influence of TM4-TM5 interface in modulating
      the water transport of ZmPIP1;2. MD simulations indicate the importance of I93
      residue from the TM2 segment of ZmPIP2;5 for the increased water transport in
      ZmPIP1;2.

PMID- 30104610
TI  - Optimising complementary soft tissue synchrotron X-ray microtomography for
      reversibly-stained central nervous system samples.
AB  - Synchrotron radiation microtomography (SRMUCT) is a nominally non-destructive 3D
      imaging technique which can visualise the internal structures of whole soft
      tissues. As a multi-stage technique, the cumulative benefits of optimising sample
      preparation, scanning parameters and signal processing can improve SRMUCT imaging
      efficiency, image quality, accuracy and ultimately, data utility. By evaluating
      different sample preparations (embedding media, tissue stains), imaging
      (projection number, propagation distance) and reconstruction (artefact
      correction, phase retrieval) parameters, a novel methodology (combining
      reversible iodine stain, wax embedding and inline phase contrast) was optimised
      for fast (~12 minutes), high-resolution (3.2-4.8 MUm diameter capillaries
      resolved) imaging of the full diameter of a 3.5 mm length of rat spinal cord.
      White-grey matter macro-features and micro-features such as motoneurons and
      capillary-level vasculature could then be completely segmented from the imaged
      volume for analysis through the shallow machine learning SuRVoS Workbench. Imaged
      spinal cord tissue was preserved for subsequent histology, establishing a
      complementary SRMUCT methodology that can be applied to study spinal cord
      pathologies or other nervous system tissues such as ganglia, nerves and brain.
      Further, our 'single-scan iterative downsampling' approach and side-by-side
      comparisons of mounting options, sample stains and phase contrast parameters
      should inform efficient, effective future soft tissue SRMUCT experiment design.

PMID- 30104611
TI  - The prognostic significance of global aberrant alternative splicing in patients
      with myelodysplastic syndrome.
AB  - Aberrant alternative splicing (AS) is a hallmark of cancer development. However,
      there are limited data regarding its clinical implications in myelodysplastic
      syndrome (MDS). In this study, we performed an in-depth analysis of global AS in
      176 primary MDS patients with 20 normal marrow transplant donors as reference. We
      found that 26.9% of the expressed genes genome-wide were aberrantly spliced in
      MDS patients compared with normal donors. These aberrant AS genes were related to
      pathways involved in cell proliferation, cell adhesion and protein degradation. A
      higher degree of global aberrant AS was associated with male gender and U2AF1
      mutation, and predicted shorter overall survival and time to leukemic change.
      Moreover, it was an independent unfavorable prognostic factor irrespective of
      age, revised international prognostic scoring system (IPSS-R) risk, and mutations
      in SRSF2, ZRSR2, ASXL1, TP53, and EZH2. With LASSO-Cox regression method, we
      constructed a simple prognosis prediction model composed of 13 aberrant AS genes,
      and demonstrated that it could well stratify MDS patients into distinct risk
      groups. To our knowledge, this is the first report demonstrating significant
      prognostic impacts of aberrant splicing on MDS patients. Further prospective
      studies in larger cohorts are needed to confirm our observations.

PMID- 30104613
TI  - Novel clinical device tracking and tissue event characterization using proximally
      placed audio signal acquisition and processing.
AB  - We propose a new and complementary approach to image guidance for monitoring
      medical interventional devices (MID) with human tissue interaction and surgery
      augmentation by acquiring acoustic emission data from the proximal end of the MID
      outside the patient to extract dynamical characteristics of the interaction
      between the distal tip and the tissue touched or penetrated by the MID. We
      conducted phantom based experiments (n = 955) to show dynamic tool/tissue
      interaction during tissue needle passage (a) and vessel perforation caused by
      guide wire artery perforation (b). We use time-varying auto-regressive (TV-AR)
      modelling to characterize the dynamic changes and time-varying maximal energy
      pole (TV-MEP) to compute subsequent analysis of MID/tissue interaction
      characterization patterns. Qualitative and quantitative analysis showed that the
      TV-AR spectrum and the TV-MEP indicated the time instants of the needle path
      through different phantom objects (a) and clearly showed a perforation versus
      other generated artefacts (b). We demonstrated that audio signals acquired from
      the proximal part of an MID could provide valuable additional information to
      surgeons during minimally invasive procedures.

PMID- 30104614
TI  - Highly-stable write-once-read-many-times switching behaviors of 1D-1R memristive
      devices based on graphene quantum dot nanocomposites.
AB  - One diode and one resistor (1D-1R) memristive devices based on inorganic Schottky
      diodes and poly(methylsilsesquioxane) (PMSSQ):graphene quantum dot (GQD) hybrid
      nanocomposites were fabricated to achieve stable memory characteristics. Current
      voltage (I-V) curves for the Al/PMSSQ:GQDs/Al/p-Si/Al devices at room temperature
      exhibited write-once, read-many-times memory (WORM) characteristics with an
      ON/OFF ratio of as large as 104 resulting from the formation of a 1D-1R
      structure. I-V characteristics of the WORM 1D-1R device demonstrated that the
      memory and the diode behaviors of the 1D-1R device functioned simultaneously. The
      retention time of the WORM 1D-1R devices could be maintained at a value larger
      than 104 s under ambient conditions. The operating mechanisms of the devices were
      analyzed on the basis of the I-V results and with the aid of the energy band
      diagram.

PMID- 30104615
TI  - Pelvic lymph node dissection during radical cystectomy for muscle-invasive
      bladder cancer.
AB  - Radical cystectomy is the gold-standard treatment option for muscle-invasive and
      metastatic bladder cancer. At the time of cystectomy, up to 25% of patients
      harbour metastatic lymph node deposits. These deposits most frequently occur in
      the obturator fossa, but can be as proximal as the interaortocaval region. Thus,
      the use of concurrent pelvic lymph node dissection (PLND) with cystectomy has
      been increasingly reported. Data from studies including many patients suggest
      substantial oncological benefit in PLND cohorts versus non-PLND cohorts,
      irrespective of pathological nodal status. Additionally, PLND provides useful
      prognostic information, including disease burden, lymph node density, and
      extracapsular extension of metastatic lymph nodes. Accordingly, the National
      Comprehensive Cancer Network guidelines advocate the use of PLND during radical
      cystectomy for muscle-invasive bladder cancer. Despite this recommendation, a
      lack of consensus exists regarding the optimal PLND template. Comparative series
      suggest that extended PLND provides improved recurrence-free survival and cancer
      specific survival compared with more limited PLND templates. More extensive
      templates (such as super-extended PLND) provide no additional survival benefit at
      the potential cost of increased operative time and patient morbidity. In addition
      to extended PLND templates, increased nodal harvest confers an oncological
      benefit in patients with node-positive disease or in patients with node-negative
      disease. Accordingly, recommendations for a minimum nodal yield have been
      proposed. Despite the growing body of evidence, formal recommendations by
      oncological and urological authoritative bodies have been limited owing to the
      lack of randomized data and level I evidence.

PMID- 30104612
TI  - Schistosoma mansoni infection is associated with quantitative and qualitative
      modifications of the mammalian intestinal microbiota.
AB  - In spite of the extensive contribution of intestinal pathology to the
      pathophysiology of schistosomiasis, little is known of the impact of schistosome
      infection on the composition of the gut microbiota of its mammalian host. Here,
      we characterised the fluctuations in the composition of the gut microbial flora
      of the small and large intestine, as well as the changes in abundance of
      individual microbial species, of mice experimentally infected with Schistosoma
      mansoni with the goal of identifying microbial taxa with potential roles in the
      pathophysiology of infection and disease. Bioinformatic analyses of bacterial 16S
      rRNA gene data revealed an overall reduction in gut microbial alpha diversity,
      alongside a significant increase in microbial beta diversity characterised by
      expanded populations of Akkermansia muciniphila (phylum Verrucomicrobia) and
      lactobacilli, in the gut microbiota of S. mansoni-infected mice when compared to
      uninfected control animals. These data support a role of the mammalian gut
      microbiota in the pathogenesis of hepato-intestinal schistosomiasis and serves as
      a foundation for the design of mechanistic studies to unravel the complex
      relationships amongst parasitic helminths, gut microbiota, pathophysiology of
      infection and host immunity.

PMID- 30104617
TI  - Scalable breakthrough.

PMID- 30104616
TI  - Universal holonomic quantum gates over geometric spin qubits with polarised
      microwaves.
AB  - A microwave shares a nonintuitive phase called the geometric phase with an
      interacting electron spin after an elastic scattering. The geometric phase,
      generally discarded as a global phase, allows universal holonomic gating of an
      ideal logical qubit, which we call a geometric spin qubit, defined in the
      degenerate subspace of the triplet spin qutrit. We here experimentally
      demonstrate nonadiabatic and non-abelian holonomic quantum gates over the
      geometric spin qubit on an electron or nitrogen nucleus. We manipulate purely the
      geometric phase with a polarised microwave in a nitrogen-vacancy centre in
      diamond under a zero-magnetic field at room temperature. We also demonstrate a
      two-qubit holonomic gate to show universality by manipulating the electron
      nucleus entanglement. The universal holonomic gates enable fast and fault
      tolerant manipulation for realising quantum repeaters interfacing between
      universal quantum computers and secure communication networks.

PMID- 30104618
TI  - Plasmonic meta-electrodes allow intracellular recordings at network level on high
      density CMOS-multi-electrode arrays.
AB  - The ability to monitor electrogenic cells accurately plays a pivotal role in
      neuroscience, cardiology and cell biology. Despite pioneering research and long
      lasting efforts, the existing methods for intracellular recording of action
      potentials on the large network scale suffer limitations that prevent their
      widespread use. Here, we introduce the concept of a meta-electrode, a planar
      porous electrode that mimics the optical and biological behaviour of three
      dimensional plasmonic antennas but also preserves the ability to work as an
      electrode. Its synergistic combination with plasmonic optoacoustic poration
      allows commercial complementary metal-oxide semiconductor multi-electrode arrays
      to record intracellular action potentials in large cellular networks. We apply
      this approach to measure signals from human-induced pluripotent stem cell-derived
      cardiac cells, rodent primary cardiomyocytes and immortalized cell types and
      demonstrate the possibility of non-invasively testing a variety of relevant
      drugs. Due to its robustness and easiness of use, we expect the method will be
      rapidly adopted by the scientific community and by pharmaceutical companies.

PMID- 30104619
TI  - Highly conductive, stretchable and biocompatible Ag-Au core-sheath nanowire
      composite for wearable and implantable bioelectronics.
AB  - Wearable and implantable devices require conductive, stretchable and
      biocompatible materials. However, obtaining composites that simultaneously fulfil
      these requirements is challenging due to a trade-off between conductivity and
      stretchability. Here, we report on Ag-Au nanocomposites composed of ultralong
      gold-coated silver nanowires in an elastomeric block-copolymer matrix. Owing to
      the high aspect ratio and percolation network of the Ag-Au nanowires, the
      nanocomposites exhibit an optimized conductivity of 41,850 S cm-1 (maximum of
      72,600 S cm-1). Phase separation in the Ag-Au nanocomposite during the solvent
      drying process generates a microstructure that yields an optimized stretchability
      of 266% (maximum of 840%). The thick gold sheath deposited on the silver nanowire
      surface prevents oxidation and silver ion leaching, making the composite
      biocompatible and highly conductive. Using the nanocomposite, we successfully
      fabricate wearable and implantable soft bioelectronic devices that can be
      conformally integrated with human skin and swine heart for continuous
      electrophysiological recording, and electrical and thermal stimulation.

PMID- 30104620
TI  - Tunable thermal transport and reversible thermal conductivity switching in
      topologically networked bio-inspired materials.
AB  - The dynamic control of thermal transport properties in solids must contend with
      the fact that phonons are inherently broadband. Thus, efforts to create
      reversible thermal conductivity switches have resulted in only modest on/off
      ratios, since only a relatively narrow portion of the phononic spectrum is
      impacted. Here, we report on the ability to modulate the thermal conductivity of
      topologically networked materials by nearly a factor of four following hydration,
      through manipulation of the displacement amplitude of atomic vibrations. By
      varying the network topology, or crosslinked structure, of squid ring teeth-based
      bio-polymers through tandem-repetition of DNA sequences, we show that this
      thermal switching ratio can be directly programmed. This on/off ratio in thermal
      conductivity switching is over a factor of three larger than the current state-of
      the-art thermal switch, offering the possibility of engineering thermally
      conductive biological materials with dynamic responsivity to heat.

PMID- 30104622
TI  - Interlayer valley excitons in heterobilayers of transition metal dichalcogenides.
AB  - Stacking different two-dimensional crystals into van der Waals heterostructures
      provides an exciting approach to designing quantum materials that can harness and
      extend the already fascinating properties of the constituents. Heterobilayers of
      transition metal dichalcogenides are particularly attractive for low-dimensional
      semiconductor optics because they host interlayer excitons-with electrons and
      holes localized in different layers-which inherit valley-contrasting physics from
      the monolayers and thereby possess various novel and appealing properties
      compared to other solid-state nanostructures. This Review presents the
      contemporary experimental and theoretical understanding of these interlayer
      excitons. We discuss their unique optical properties arising from the underlying
      valley physics, the strong many-body interactions and electrical control
      resulting from the electric dipole moment, and the unique effects of a moire
      superlattice on the interlayer exciton potential landscape and optical
      properties.

PMID- 30104621
TI  - Gold nanoparticle biodissolution by a freshwater macrophyte and its associated
      microbiome.
AB  - Predicting nanoparticle fate in aquatic environments requires mimicking of
      ecosystem complexity to observe the geochemical processes affecting their
      behaviour. Here, 12 nm Au nanoparticles were added weekly to large-scale
      freshwater wetland mesocosms. After six months, ~70% of Au was associated with
      the macrophyte Egeria densa, where, despite the thermodynamic stability of Au0 in
      water, the pristine Au0 nanoparticles were fully oxidized and complexed to
      cyanide, hydroxyls or thiol ligands. Extracted biofilms growing on E. densa
      leaves were shown to dissolve Au nanoparticles within days. The Au biodissolution
      rate was highest for the biofilm with the lowest prevalence of metal-resistant
      taxa but the highest ability to release cyanide, known to promote Au0 oxidation
      and complexation. Macrophytes and the associated microbiome thus form a
      biologically active system that can be a major sink for nanoparticle accumulation
      and transformations. Nanoparticle biotransformation in these compartments should
      not be ignored, even for nanoparticles commonly considered to be stable in the
      environment.

PMID- 30104623
TI  - Creating solvation environments in heterogeneous catalysts for efficient biomass
      conversion.
AB  - Chemical transformations are highly sensitive toward changes in the solvation
      environment and solvents have long been used to control their outcome. Reactions
      display unique performance in solvents like ionic liquids or DMSO, however,
      isolating products from them is cumbersome and energy-consuming. Here, we develop
      promising alternatives by constructing solvent moieties into porous materials,
      which in turn serve as platforms for introducing catalytic species. Due to the
      high density of the solvent moieties, these porous solid solvents (PSSs) retain
      solvation ability, which greatly influences the performance of incorporated
      active sites via concerted non-covalent substrate-catalyst interactions. As a
      proof-of-concept, the -SO3H-incorporated PSSs exhibit high yields of fructose to
      5-hydroxymethylfurfural in THF, which exceeds the best results reported using
      readily separable solvents and even rivals those in ionic liquids or DMSO. Given
      the wide application, our strategy provides a step forward towards sustainable
      synthesis by eliminating the concerns with separation unfriendly solvents.

PMID- 30104624
TI  - In vivo imaging reveals unique neutrophil transendothelial migration patterns in
      inflamed intestines.
AB  - Neutrophil (PMN) infiltration of the intestinal mucosa is a hallmark of
      gastrointestinal inflammation, with significant implications for host defense,
      injury and repair. However, phenotypic and mechanistic aspects of PMN recruitment
      in inflamed intestines have not been explored in vivo. Using novel epithelial/PMN
      fluorescence reporter mice, advanced intravital imaging and 3D reconstruction
      analysis, we mapped the microvasculature architecture across the intestinal
      layers and determined that in response to Salmonella/endotoxin-induced
      inflammation, PMN transendothelial migration (TEM) was restricted to submucosal
      vessels. PMN TEM was not observed in villus or crypt vessels, proximal to the
      epithelium that underlies the intestinal lumen, and was partially dependent on (C
      X-C motif) ligands 1 (CXCL1) and 2 (CXCL2) expression, which was found to be
      elevated in the submucosa layer. Restricted PMN extravasation at the submucosa
      and subsequent PMN interstitial migration may serve as a novel regulatory step of
      PMN effector function and recruitment to the luminal space in inflamed
      intestines.

PMID- 30104627
TI  - Chronic intestinal inflammation in mice expressing viral Flip in epithelial
      cells.
AB  - Viruses are present in the intestinal microflora and are currently discussed as a
      potential causative mechanism for the development of inflammatory bowel disease.
      A number of viruses, such as Human Herpesvirus-8, express homologs to cellular
      FLIPs, which are major contributors for the regulation of epithelial cell death.
      In this study we analyzed the consequences of constitutive expression of HHV8
      viral FLIP in intestinal epithelial cells (IECs) in mice. Surprisingly,
      expression of vFlip disrupts tissue homeostasis and induces severe intestinal
      inflammation. Moreover vFlipIEC-tg mice showed reduced Paneth cell numbers,
      associated with excessive necrotic cell death. On a molecular level vFlip
      expression altered classical and alternative NFkappaB activation. Blocking of
      alternative NFkappaB signaling by deletion of Ikka in vivo largely protected mice
      from inflammation and Paneth cell loss induced by vFLIP. Collectively, our data
      provide functional evidence that expression of a single viral protein in IECs can
      be sufficient to disrupt epithelial homeostasis and to initiate chronic
      intestinal inflammation.

PMID- 30104625
TI  - C3a is required for ILC2 function in allergic airway inflammation.
AB  - Aberrant type 2 responses underlie the pathologies in allergic diseases like
      asthma, yet, our understanding of the mechanisms that drive them remains limited.
      Recent evidence suggests that dysregulated innate immune factors can perpetuate
      asthma pathogenesis. In susceptible individuals, allergen exposure triggers the
      activation of complement, a major arm of innate immunity, leading to the aberrant
      generation of the C3a anaphylatoxin. C3 and C3a have been shown to be important
      for the development of Th2 responses, yet remarkably, the mechanisms by which C3a
      regulates type 2 immunity are relatively unknown. We demonstrate a central role
      for C3a in driving type 2 innate lymphoid cells (ILC2)-mediated inflammation in
      response to allergen and IL-33. Our data suggests that ILC2 recruitment is C3a
      dependent. Further, we show that ILC2s directly respond to C3a, promoting type 2
      responses by specifically: (1) inducing IL-13 and granulocyte-macrophage colony
      stimulating factor, whereas inhibiting IL-10 production from ILC2; and (2)
      enhancing their antigen-presenting capability during ILC-T-cell cross-talk. In
      summary, we identify a novel mechanism by which C3a can mediate aberrant type 2
      responses to aeroallergen exposure, which involves a yet unrecognized cross-talk
      between two major innate immune components-complement and group 2 innate lymphoid
      cells.

PMID- 30104628
TI  - Harald von Boehmer 1942-2018.

PMID- 30104629
TI  - Human germinal center transcriptional programs are de-synchronized in B cell
      lymphoma.
AB  - Most adult B cell lymphomas originate from germinal center (GC) B cells, but it
      is unclear to what extent B cells in overt lymphoma retain the functional
      dynamics of GC B cells or are blocked at a particular stage of the GC reaction.
      Here we used integrative single-cell analysis of phenotype, gene expression and
      variable-region sequence of the immunoglobulin heavy-chain locus to track the
      characteristic human GC B cell program in follicular lymphoma B cells. By
      modeling the cyclic continuum of GC B cell transitional states, we identified
      characteristic patterns of synchronously expressed gene clusters. GC-specific
      gene-expression synchrony was lost in single lymphoma B cells. However, distinct
      follicular lymphoma-specific cell states co-existed within single patient
      biopsies. Our data show that lymphoma B cells are not blocked in a GC B cell
      state but might adopt new dynamic modes of functional diversity, which opens the
      possibility of novel definitions of lymphoma identity.

PMID- 30104630
TI  - Silencing of TLM B cells by chronic HIV infection.

PMID- 30104626
TI  - Dietary DHA amplifies LXA4 circuits in tissues and lymph node PMN and is
      protective in immune-driven dry eye disease.
AB  - Recently identified regulatory PMN control immune-driven dry eye disease (DED) in
      females by producing the arachidonic acid (omega-6)-derived specialized pro
      resolving mediator (SPM), LXA4, in lymph nodes. Dietary omega-3 docosahexaenoic
      acid (DHA) is protective in DED but mechanisms of action remain elusive. DHA is
      converted to omega-3 SPMs by PMN via the same lipoxygenases (LOX) that generate
      LXA4. We investigated if dietary DHA amplifies SPM formation and affects T
      effector cell function and/or regulatory PMN in DED. DED was induced in mice on a
      DHA-enriched or omega-3-deficient diet. DHA deficiency amplified DED with marked
      sex-specific differences. Dietary DHA protection against dry eye disease
      correlated with increased PMN levels in lymph nodes, ocular tissues, and
      unexpectedly, selective amplification of LXA4 tissue levels. Dietary DHA
      increased 12/15-LOX and decreased 5-LOX expression in lymph nodes and isolated
      lymph node PMN, which correlated with amplified LXA4 formation. Acute DHA
      treatment rescued DHA-deficient females from exaggerated DED by amplifying lymph
      node LXA4 formation, increasing Treg and decreasing TH1 and TH17 effector cells.
      Our results identify DHA regulation of LXA4 producing PMN in ocular tissues and
      lymph nodes in health and immune disease as novel mechanism and determinant for T
      cell responses to routine ocular injury or stress signals.

PMID- 30104631
TI  - Kimishige Ishizaka 1925-2018.

PMID- 30104632
TI  - Singling out the out-of-tune in lymphoma.

PMID- 30104633
TI  - IgG3 regulates tissue-like memory B cells in HIV-infected individuals.
AB  - Immunoglobulin G3 (IgG3) has an uncertain role in the response to infection with
      and vaccination against human immunodeficiency virus (HIV). Here we describe a
      regulatory role for IgG3 in dampening the immune system-activating effects of
      chronic HIV viremia on B cells. Secreted IgG3 was bound to IgM-expressing B cells
      in vivo in HIV-infected chronically viremic individuals but not in early-viremic
      or aviremic individuals. Tissue-like memory (TLM) B cells, a population expanded
      by persistent HIV viremia, bound large amounts of IgG3. IgG3 induced clustering
      of B cell antigen receptors (BCRs) on the IgM+ B cells, which was mediated by
      direct interactions between soluble IgG3 and membrane IgM of the BCR (IgM-BCR).
      The inhibitory IgG receptor CD32b (FcgammaRIIb), complement component C1q and
      inflammatory biomarker CRP contributed to the binding of secreted IgG3 onto IgM
      expressing B cells of HIV-infected individuals. Notably, IgG3-bound TLM B cells
      were refractory to IgM-BCR stimulation, thus demonstrating that IgG3 can regulate
      B cells during chronic activation of the immune system.

PMID- 30104634
TI  - The immunoproteasome and thymoproteasome: functions, evolution and human disease.
AB  - The basic principle of adaptive immunity is to strictly discriminate between self
      and non-self, and a central challenge to overcome is the enormous variety of
      pathogens that might be encountered. In cell-mediated immunity, immunological
      discernment takes place at a molecular or cellular level. Central to both
      mechanisms of discernment is the generation of antigenic peptides associated with
      MHC class I molecules, which is achieved by a proteolytic complex called the
      proteasome. To adequately accomplish the discrimination between self and non-self
      that is essential for adaptive immunity and self-tolerance, two proteasome
      subtypes have evolved via gene duplication: the immunoproteasome and the
      thymoproteasome. In this Review, we describe various aspects of these immunity
      dedicated proteasomes, from their discovery to recent findings.

PMID- 30104635
TI  - A proximity-tagging system to identify membrane protein-protein interactions.
AB  - The communication between cells and between cellular organelles is often
      controlled by the interaction of membrane proteins. Although many methods for the
      detection of protein-protein interactions (PPIs) exist, membrane PPIs remain
      difficult to detect. Here we developed a proximity-based tagging system, PUP-IT
      (pupylation-based interaction tagging), to identify membrane protein
      interactions. In this approach, a small protein tag, Pup, is applied to proteins
      that interact with a PafA-fused bait, enabling transient and weak interactions to
      be enriched and detected by mass spectrometry. Pup does not diffuse from the
      enzyme, which allows high-specificity labeling. We applied this approach to CD28,
      a critical costimulatory receptor for T lymphocyte activation, and identified
      known CD28 binding partners and multiple potential interacting proteins. In
      addition, we demonstrated that this method can identify the interaction between a
      cell surface receptor and its ligand.

PMID- 30104636
TI  - The GAGOme: a cell-based library of displayed glycosaminoglycans.
AB  - Glycosaminoglycans (GAGs) are essential polysaccharides in normal physiology and
      disease. However, understanding of the contribution of specific GAG structures to
      specific biological functions is limited, largely because of the great structural
      heterogeneity among GAGs themselves, as well as technical limitations in the
      structural characterization and chemical synthesis of GAGs. Here we describe a
      cell-based method to produce and display distinct GAGs with a broad repertoire of
      modifications, a library we refer to as the GAGOme. By using precise gene
      editing, we engineered a large panel of Chinese hamster ovary cells with knockout
      or knock-in of the genes encoding most of the enzymes involved in GAG
      biosynthesis, to generate a library of isogenic cell lines that differentially
      display distinct GAG features. We show that this library can be used for cell
      based binding assays, recombinant expression of proteoglycans with distinct GAG
      structures, and production of distinct GAG chains on metabolic primers that may
      be used for the assembly of GAG glycan microarrays.

PMID- 30104637
TI  - Evaluation of Skin Hardness as a Physiological Sign of Human Thermal Status.
AB  - This is the first ever proposal to use skin hardness as a physiological sign by
      which to estimate human thermal status and to verify its effectiveness and
      independence in relation to the two conventional signs: skin temperature and skin
      conductance. We propose a novel TSV model adding skin hardness to the
      conventional TSV model for better estimation of human thermal status with higher
      accuracy and lower error. We survey individual thermal sensation from 30 subjects
      under four different thermal conditions (normal, warm, hot, and cold); while
      measuring skin hardness along with the two conventional physiological signs. The
      novel model for estimation of thermal status from all three signs increases R2 by
      17.4% and decreases error by 23.5%, compared to the conventional model using two
      signs. The novel TSV model has potential for applications to human-machine
      interaction systems for better estimation of human thermal status.

PMID- 30104638
TI  - Highly efficient capture of cancer cells expressing EGFR by microfluidic methods
      based on antigen-antibody association.
AB  - Epidermal growth factor receptor (EGFR) was evaluated as a target antigen for
      cancer cell capture by microfluidic methods based on antigen-antibody
      association. A polymer CTC-chip microfluidic device was surface-functionalized
      with three different anti-EGFR antibodies and used to capture EGFR-expressing
      cancer cells. Capture efficacy depended on the type of antibody used, and
      cetuximab efficiently captured cancer cell lines that had a wide range of EGFR
      expression. Capture efficiency was analyzed from the viewpoint of antigen
      antibody association in a kinetic process, i.e., cell rolling well-known in
      leukocyte adhesion, and antibodies with a smaller dissociation constant were
      shown to result in more efficient capture. Moreover, a lower limit of cellular
      EGFR expression level for the capture was estimated and methods to decrease the
      limit were discussed based on densities of anti-EGFR antibody on the device
      surface.

PMID- 30104640
TI  - Freeze-on limits bed strength beneath sliding glaciers.
AB  - Discharge from sliding outlet glaciers controls uncertainty in projections for
      future sea level. Remarkably, over 90% of glacial area is subject to
      gravitational driving stresses below 150 kPa (median ~70 kPa). Longstanding
      explanations that appeal to the shear-thinning rheology of ice tend to
      overpredict driving stresses and are restricted to areas where ice sheets only
      deform (roughly 50%). Over the more dynamic portions that slide, driving stresses
      must be balanced by thermo-mechanical interactions that control basal strength.
      Here we show that median bed strength is comparable to a threshold effective
      stress set by ice-liquid surface energy and till pore size. Above this threshold,
      ice infiltrates sediment to produce basal layers of debris-rich ice, even where
      net melting takes place. We demonstrate that the narrow range of inferred bed
      strengths can be explained by the mechanical resistance to sliding where
      roughness is enhanced by heterogeneous freeze-on.

PMID- 30104639
TI  - Myocardial fatty acid uptake through CD36 is indispensable for sufficient
      bioenergetic metabolism to prevent progression of pressure overload-induced heart
      failure.
AB  - The energy metabolism of the failing heart is characterized by reduced fatty acid
      (FA) oxidation and an increase in glucose utilization. However, little is known
      about how energy metabolism-function relationship is relevant to pathophysiology
      of heart failure. Recent study showed that the genetic deletion of CD36 (CD36KO),
      which causes reduction in FA use with an increased reliance on glucose,
      accelerates the progression from compensated hypertrophy to heart failure. Here,
      we show the mechanisms by which CD36 deletion accelerates heart failure in
      response to pressure overload. CD36KO mice exhibited contractile dysfunction and
      death from heart failure with enhanced cardiac hypertrophy and interstitial
      fibrosis when they were subjected to transverse aortic constriction (TAC). The
      pool size in the TCA cycle and levels of high-energy phosphate were significantly
      reduced in CD36KO-TAC hearts despite an increase in glycolytic flux. De novo
      synthesis of non-essential amino acids was facilitated in CD36KO-TAC hearts,
      which could cause a further decline of the pool size. The ingestion of a diet
      enriched in medium-chain FA improved cardiac dysfunction in CD36KO-TAC hearts.
      These findings suggest that myocardial FA uptake through CD36 is indispensable
      for sufficient ATP production and for preventing an increased glycolytic flux
      mediated structural remodeling during pressure overload-induced hypertrophy.

PMID- 30104641
TI  - Effect of storage conditions on salivary polyamines quantified via liquid
      chromatography-mass spectrometry.
AB  - Salivary polyamines are potential non-invasive tools for screening various types
      of cancers. For clinical use, the reproducibility of these metabolites should be
      evaluated under various storage conditions, including duration and temperature,
      to establish standard operating protocols. Polyamines and amino acids in
      unstimulated whole saliva were quantified via liquid chromatography-mass
      spectrometry. Concentrations of time course samples were analysed after short
      term storage for up to 240 min and long-term storage for up to 8 days under
      various storage conditions. As expected, storage at the lowest temperature (-18 
      degrees C) exerted the least pronounced effects on the quantified values in both
      tests. At a higher temperature, polyamines were more stable than amino acids, as
      evident from polyamine profiling. Addition of ethanol significantly stabilized
      polyamine profiles even at a higher temperature. Comparative processing of saliva
      revealed a minor effect of the solvent, whereas drying had a more prominent
      effect on polyamine profiles. Computational analyses evaluated the ability of
      polyamines to discriminate pancreatic cancer from controls. Repeated noise added
      tests were designed on the basis of the results of the storage tests; these
      analyses confirmed that the discriminative abilities were robust. These data
      contribute to the standardization of salivary storage conditions, thereby
      highlighting the clinical utility of saliva.

PMID- 30104643
TI  - Plasma metabolomic analysis in mature female common bottlenose dolphins:
      profiling the characteristics of metabolites after overnight fasting by
      comparison with data in beagle dogs.
AB  - The present study was aimed at determining the characteristics of plasma
      metabolites in bottlenose dolphins to provide a greater understanding of their
      metabolism and to obtain information for the health management of cetaceans.
      Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) and liquid
      chromatograph-time-of-flight mass spectrometry (LC-TOFMS) were conducted on
      plasma samples after overnight fasting from three common bottlenose dolphins as
      well as three beagle dogs (representative terrestrial carnivores) for comparison.
      In total, 257 and 227 plasma metabolites were identified in the dolphins and the
      dogs, respectively. Although a small number of animals were used for each
      species, the heatmap patterns, a principal component analysis and a cluster
      analysis confirmed that the composition of metabolites could be segregated from
      each other. Of 257 compounds detected in dolphin plasma, 24 compounds including
      branched amino acids, creatinine, urea, and methylhistidine were more abundant
      than in dogs; 26 compounds including long-chained acyl-carnitines and fatty
      acids, astaxanthin, and pantothenic acid were detected only in dolphins. In
      contrast, 25 compounds containing lactic acid and glycerol 3-phosphate were lower
      in dolphins compared to dogs. These data imply active protein metabolism,
      differences in usage of lipids, a unique urea cycle, and a low activity of the
      glycolytic pathway in dolphins.

PMID- 30104642
TI  - Neonatal brain injury causes cerebellar learning deficits and Purkinje cell
      dysfunction.
AB  - Premature infants are more likely to develop locomotor disorders than term
      infants. In a chronic sub-lethal hypoxia (Hx) mouse model of neonatal brain
      injury, we recently demonstrated the presence of cellular and physiological
      changes in the cerebellar white matter. We also observed Hx-induced delay in
      Purkinje cell (PC) arborization. However, the behavioral consequences of these
      cellular alterations remain unexplored. Using the Erasmus Ladder to study
      cerebellar behavior, we report the presence of locomotor malperformance and long
      term cerebellar learning deficits in Hx mice. Optogenetics experiments in Hx mice
      reveal a profound reduction in spontaneous and photoevoked PC firing frequency.
      Finally, treatment with a gamma-aminobutyric acid (GABA) reuptake inhibitor
      partially rescues locomotor performance and improves PC firing. Our results
      demonstrate a long-term miscoordination phenotype characterized by locomotor
      malperformance and cerebellar learning deficits in a mouse model of neonatal
      brain injury. Our findings also implicate the developing GABA network as a
      potential therapeutic target for prematurity-related locomotor deficits.

PMID- 30104644
TI  - Uphill production of dihydrogen by enzymatic oxidation of glucose without an
      external energy source.
AB  - Chemical systems do not allow the coupling of energy from several simple
      reactions to drive a subsequent reaction, which takes place in the same medium
      and leads to a product with a higher energy than the one released during the
      first reaction. Gibbs energy considerations thus are not favorable to drive e.g.,
      water splitting by the direct oxidation of glucose as a model reaction. Here, we
      show that it is nevertheless possible to carry out such an energetically uphill
      reaction, if the electrons released in the oxidation reaction are temporarily
      stored in an electromagnetic system, which is then used to raise the electrons'
      potential energy so that they can power the electrolysis of water in a second
      step. We thereby demonstrate the general concept that lower energy delivering
      chemical reactions can be used to enable the formation of higher energy consuming
      reaction products in a closed system.

PMID- 30104645
TI  - Bifidobacterium breve MRx0004 protects against airway inflammation in a severe
      asthma model by suppressing both neutrophil and eosinophil lung infiltration.
AB  - Asthma is a phenotypically heterogeneous disease. In severe asthma, airway
      inflammation can be predominantly eosinophilic, neutrophilic, or mixed. Only a
      limited number of drug candidates are in development to address this unmet
      clinical need. Live biotherapeutics derived from the gut microbiota are a
      promising new therapeutic area. MRx0004 is a commensal Bifidobacterium breve
      strain isolated from the microbiota of a healthy human. The strain was tested
      prophylactically and therapeutically by oral gavage in a house dust mite mouse
      model of severe asthma. A strong reduction of neutrophil and eosinophil
      infiltration was observed in lung bronchoalveolar lavage fluid following MRx0004
      treatment. Peribronchiolar and perivascular immunopathology was also reduced.
      MRx0004 increased lung CD4+CD44+ cells and CD4+FoxP3+ cells and decreased
      activated CD11b+ dendritic cells. Cytokine analysis of lung tissue revealed
      reductions of pro-inflammatory cytokines and chemokines involved in neutrophil
      migration. In comparison, anti-IL-17 antibody treatment effectively reduced
      neutrophilic infiltration and increased CD4+FoxP3+ cells, but it induced lung
      eosinophilia and did not decrease histopathology scores. We have demonstrated
      that MRx0004, a microbiota-derived bacterial strain, can reduce both neutrophilic
      and eosinophilic infiltration in a mouse model of severe asthma. This novel
      therapeutic is a promising next-generation drug for management of severe asthma.

PMID- 30104646
TI  - Comparative toxicity of synchrotron and conventional radiation therapy based on
      total and partial body irradiation in a murine model.
AB  - Synchrotron radiation can facilitate novel radiation therapy modalities such as
      microbeam radiation therapy (MRT) and high dose-rate synchrotron broad-beam
      radiation therapy (SBBR). Both of these modalities have unique physical
      properties that could be exploited for an improved therapeutic effect. While pre
      clinical studies report promising normal tissue sparing phenomena, systematic
      toxicity data are still required. Our objective was to characterise the toxicity
      of SBBR and MRT and to calculate equivalent doses of conventional radiation
      therapy (CRT). A dose-escalation study was performed on C57BLJ/6 mice using total
      body and partial body irradiations. Dose-response curves and TD50 values were
      subsequently calculated using PROBIT analysis. For SBBR at dose-rates of 37 to 41
      Gy/s, we found no evidence of a normal tissue sparing effect relative to CRT. Our
      findings also show that the MRT valley dose, rather than the peak dose, best
      correlates with CRT doses for acute toxicity. Importantly, longer-term weight
      tracking of irradiated animals revealed more pronounced growth impairment
      following MRT compared to both SBBR and CRT. Overall, this study provides the
      first in vivo dose-equivalence data between MRT, SBBR and CRT and presents
      systematic toxicity data for a range of organs that can be used as a reference
      point for future pre-clinical work.

PMID- 30104648
TI  - How to solve the gender expression gap.

PMID- 30104647
TI  - Combining spectroscopic and isotopic techniques gives a dynamic view of
      phosphorus cycling in soil.
AB  - Current understanding of phosphorus (P) cycling in soils can be enhanced by
      integrating previously discrete findings concerning P speciation, exchange
      kinetics, and the underlying biological and geochemical processes. Here, we
      combine sequential extraction with P K-edge X-ray absorption spectroscopy and
      isotopic methods (33P and 18O in phosphate) to characterize P cycling on a
      climatic gradient in Hawaii. We link P pools to P species and estimate the
      turnover times for commonly considered P pools. Dissolved P turned over in
      seconds, resin-extractable P in minutes, NaOH-extractable inorganic P in weeks to
      months, and HCl-extractable P in years to millennia. Furthermore, we show that in
      arid-zone soils, some primary mineral P remains even after 150 ky of soil
      development, whereas in humid-zone soils of the same age, all P in all pools has
      been biologically cycled. The integrative information we provide makes possible a
      more dynamic, process-oriented conceptual model of P cycling in soils.

PMID- 30104649
TI  - Genomic imprinting mediates dosage compensation in a young plant XY system.
AB  - Sex chromosomes have repeatedly evolved from a pair of autosomes. Consequently, X
      and Y chromosomes initially have similar gene content, but ongoing Y degeneration
      leads to reduced expression and eventual loss of Y genes1. The resulting
      imbalance in gene expression between Y genes and the rest of the genome is
      expected to reduce male fitness, especially when protein networks have components
      from both autosomes and sex chromosomes. A diverse set of dosage compensating
      mechanisms that alleviates these negative effects has been described in animals2
      4. However, the early steps in the evolution of dosage compensation remain
      unknown, and dosage compensation is poorly understood in plants5. Here, we
      describe a dosage compensation mechanism in the evolutionarily young XY sex
      determination system of the plant Silene latifolia. Genomic imprinting results in
      higher expression from the maternal X chromosome in both males and females. This
      compensates for reduced Y expression in males, but results in X overexpression in
      females and may be detrimental. It could represent a transient early stage in the
      evolution of dosage compensation. Our finding has striking resemblance to the
      first stage proposed by Ohno6 for the evolution of X inactivation in mammals.

PMID- 30104650
TI  - Dynamic and spatial restriction of Polycomb activity by plant histone
      demethylases.
AB  - Targeted changes in chromatin state at thousands of genes are central to
      eukaryotic development. RELATIVE OF EARLY FLOWERING 6 (REF6) is a Jumonji-type
      histone demethylase that counteracts Polycomb repressive complex 2 (PRC2)
      mediated gene silencing in plants and was reported to select its binding sites in
      a direct, sequence-specific manner1-3. Here we show that REF6 and its two close
      paralogues determine spatial 'boundaries' of the repressive histone H3K27me3 mark
      in the genome and control the tissue-specific release from PRC2-mediated gene
      repression. Targeted mutagenesis revealed that these histone demethylases display
      pleiotropic, redundant functions in plant development, several of which depend on
      trans factor-mediated recruitment. Thus, Jumonji-type histone demethylases
      restrict repressive chromatin domains and contribute to tissue-specific gene
      activation via complementary targeting mechanisms.

PMID- 30104652
TI  - Routes to genetic gain in potato.

PMID- 30104651
TI  - Generation of self-compatible diploid potato by knockout of S-RNase.
AB  - Re-domestication of potato into an inbred line-based diploid crop propagated by
      seed represents a promising alternative to traditional clonal propagation of
      tetraploid potato, but self-incompatibility has hindered the development of
      inbred lines. To address this problem, we created self-compatible diploid
      potatoes by knocking out the self-incompatibility gene S-RNase using the CRISPR
      Cas9 system. This strategy opens new avenues for diploid potato breeding and will
      also be useful for studying other self-incompatible crops.

PMID- 30104653
TI  - Comparative analysis of surface coating properties of five hydrophobins from
      Aspergillus nidulans and Trichoderma reseei.
AB  - Fungal hydrophobins are small amphiphilic proteins that self-assemble into
      monolayers on hydrophobic:hydrophilic interfaces and can be used for surface
      coatings. Because e.g. Aspergillus nidulans contains six different hydrophobins,
      it is likely that they have different properties and are used for different
      "applications" in the fungus. We established a method for recombinant production
      of different class hydrophobins in Escherichia coli. We produced DewA, DewC,
      DewD, DewE from A. nidulans and HFBI from Trichoderma reesei and compared surface
      coating properties of these hydrophobins. All tested proteins formed coatings on
      glass, strongly increasing the hydrophobicity of the surface, and showed emulsion
      stabilizing properties. But whereas the typical class I hydrophobin DewA formed
      the most stable coating on glass, the intermediate class hydrophobins DewE and
      DewD were more effective in stabilization of oil:water emulsions. This work gives
      insights into correlations between structural characteristics of hydrophobins and
      their behaviour as surface binding agents. It could help with the clarification
      of their biological functions and lead to novel biotechnological applications.

PMID- 30104654
TI  - How PERK kinase conveys stress signals to nuclear factor-kappaB to mediate
      estrogen-induced apoptosis in breast cancer cells?

PMID- 30104655
TI  - Fructose and prostate cancer: toward an integrated view of cancer cell
      metabolism.
AB  - Activation of glucose transporter-1 (Glut-1) gene expression is a molecular
      feature of cancer cells that increases glucose uptake and metabolism. Increased
      glucose uptake is the basis for the clinical localization of primary tumors using
      positron emission tomography (PET) and 2-deoxy-2-[18F]-fluoro-D-glucose (FDG) as
      a radiotracer. However, previous studies have demonstrated that a considerable
      number of cancers, which include prostate cancer (CaP), express low to
      undetectable levels of Glut-1 and that FDG-PET has limited clinical applicability
      in CaP. This observation could be explained by a low metabolic activity of CaP
      cells that may be overcome using different hexoses, such as fructose, as the
      preferred energy source. However, these hypotheses have not been examined
      critically in CaP. This review article summarizes what is currently known about
      transport and metabolism of hexoses, and more specifically fructose, in CaP and
      provides experimental evidences indicating that CaP cells may have increased
      capacity to transport and metabolize fructose in vitro and in vivo. Moreover,
      this review highlights recent findings that allow better understanding of how
      metabolism of fructose may regulate cancer cell proliferation and how fructose
      uptake and metabolism, through the de novo lipogenesis pathway, may provide new
      opportunities for CaP early diagnosis, staging, and treatment.

PMID- 30104656
TI  - MRI in prostate cancer diagnosis: do we need to add standard sampling? A review
      of the last 5 years.
AB  - INTRODUCTION: In recent years, evidence has accrued to support the introduction
      of multiparametric magnetic resonance imaging (mpMRI) in the prostate cancer
      diagnostic pathway. The exact role of mpMRI in different settings is not widely
      agreed. In this review, we look at the use of MRI in three groups of men: biopsy
      naive men, those with a previous negative biopsy and those with a previous
      positive biopsy suitable for active surveillance. MATERIAL AND METHODS: An
      electronic MEDLINE/PubMed search up to 24th January 2018 was performed, using the
      search terms (prostate cancer OR prostate adenocarcinoma) AND (MRI OR magnetic
      resonance) AND (biopsy naive OR active surveillance OR prior negative biopsy OR
      no prior biopsy). Only those studies which reported detection rates of standard
      biopsy and MRI-targeted biopsy, where all men had both an MRI and standard biopsy
      were included. RESULTS: In total 34 articles were included (14 biopsy naive, 10
      prior negative biopsy, and 10 prior positive biopsy). MRI-targeted biopsy
      consistently resulted in greater detection of clinically significant prostate
      cancer, and a lower detection of clinically insignificant prostate cancer, across
      all three patient populations. This effect was most prominent in men with at
      least one previous negative biopsy, and least prominent in men on active
      surveillance. In the presence of a negative mpMRI detection of csPCa found at
      systematic biopsy ranged from 0 to 20%. CONCLUSIONS: MRI-targeted biopsy is more
      efficient than standard biopsy in detecting clinically significant disease in men
      with a positive MRI, and results in less detection of clinically insignificant
      cancer. In men with a negative MRI, a significant minority of men will have
      clinically significant cancer detected on systematic biopsy.

PMID- 30104657
TI  - Otorhinolaryngological profile and surgical intervention in patients with
      HIV/AIDS.
AB  - Little is known about the diagnosis and surgical management of head and neck
      conditions in patients with HIV/AIDS. This study was conducted to characterize
      the otorhinolaryngological (ORL) profiles, surgical interventions and outcomes in
      patients with HIV/AIDS. This retrospective study included patients with HIV/AIDS
      who underwent head and neck surgeries at You'an Hospital from November 2009 to
      February 2017. Patients' ages, ORL diagnoses and surgical interventions for all
      ORL surgeries were recorded. We identified 57 ORL surgeries in 52 patients during
      this time. The mean age of the patients was 37.7 +/- 12.8 years, with a
      predominance of male patients (90.4%). The three most common surgical diagnoses
      were chronic tonsillitis (19.3%), followed by chronic rhinosinusitis (CRS)
      (14.0%) and vocal polyps (8.8%). The three most common surgeries performed were
      tonsillectomy (19.3%), endoscopic sinus surgery + radiofrequency ablation of the
      inferior turbinate (14.0%) and vocal cord polypectomy (8.8%). No mortality
      occurred in the 30 days after surgery, but 2 patients (3.8%) developed post
      operative surgical site infections (SSI). These findings provide information on
      ORL manifestations and surgical interventions in patients with HIV/AIDS and may
      assist in the achievement of the most appropriate treatments for this patient
      population.

PMID- 30104658
TI  - Bipolar mood cycles associated with lunar entrainment of a circadian rhythm.
AB  - In bipolar disorder, episodes of depression and mania are associated with
      dramatic disturbances in sleep, which experiments show are likely to contribute
      to the pathogenesis of the episodes. A recent finding that 18 patients' manic
      depressive cycles oscillated in synchrony with biweekly surges in amplitude of
      the moon's tides provided a clue to the cause of the sleep-disturbances. Analyses
      of one of the patients' sleep-wake cycles suggest that his mood cycles arose when
      a circadian rhythm that normally is entrained to dawn and controls the daily
      onset of wakefulness became entrained instead to 24.8-h recurrences of every
      second 12.4-h tidal cycle. The finding provides the basis for a comprehensive
      description of the pathogenesis and pathophysiology of the mood cycle.

PMID- 30104659
TI  - The Gpr1-regulated Sur7 family protein Sfp2 is required for hyphal growth and
      cell wall stability in the mycoparasite Trichoderma atroviride.
AB  - Mycoparasites, e.g. fungi feeding on other fungi, are prominent within the genus
      Trichoderma and represent a promising alternative to chemical fungicides for
      plant disease control. We previously showed that the seven-transmembrane receptor
      Gpr1 regulates mycelial growth and asexual development and governs mycoparasitism
      related processes in Trichoderma atroviride. We now describe the identification
      of genes being targeted by Gpr1 under mycoparasitic conditions. The identified
      gene set includes a candidate, sfp2, encoding a protein of the fungal-specific
      Sur7 superfamily, whose upregulation in T. atroviride upon interaction with a
      fungal prey is dependent on Gpr1. Sur7 family proteins are typical residents of
      membrane microdomains such as the membrane compartment of Can1 (MCC)/eisosome in
      yeast. We found that GFP-labeled Gpr1 and Sfp2 proteins show partly overlapping
      localization patterns in T. atroviride hyphae, which may point to shared
      functions and potential interaction during signal perception and endocytosis.
      Deletion of sfp2 caused heavily altered colony morphology, defects in polarized
      growth, cell wall integrity and endocytosis, and significantly reduced
      mycoparasitic activity, whereas sfp2 overexpression enhanced full overgrowth and
      killing of the prey. Transcriptional activation of a chitinase specific for
      hyphal growth and network formation and strong downregulation of chitin synthase
      encoding genes were observed in Deltasfp2. Taken together, these findings imply
      crucial functions of Sfp2 in hyphal morphogenesis of T. atroviride and its
      interaction with prey fungi.

PMID- 30104660
TI  - Mitochondrial ribosomal proteins involved in tellurite resistance in yeast
      Saccharomyces cerevisiae.
AB  - A considerable body of evidence links together mitochondrial dysfunctions, toxic
      action of metalloid oxyanions, and system and neurodegenerative disorders. In
      this study we have used the model yeast Saccharomyces cerevisiae to investigate
      the genetic determinants associated with tellurite resistance/sensitivity.
      Nitrosoguanidine-induced K2TeO3-resistant mutants were isolated, and one of these
      mutants, named Sc57-Te5R, was characterized. Both random spore analysis and
      tetrad analysis and growth of heterozygous (TeS/Te5R) diploid from Sc57-Te5R
      mutant revealed that nuclear and recessive mutation(s) was responsible for the
      resistance. To get insight into the mechanisms responsible for K2TeO3-resistance,
      RNA microarray analyses were performed with K2TeO3-treated and untreated Sc57
      Te5R cells. A total of 372 differentially expressed loci were identified
      corresponding to 6.37% of the S. cerevisiae transcriptome. Of these, 288
      transcripts were up-regulated upon K2TeO3 treatment. About half of up-regulated
      transcripts were associated with the following molecular functions:
      oxidoreductase activity, structural constituent of cell wall, transporter
      activity. Comparative whole-genome sequencing allowed us to identify nucleotide
      variants distinguishing Sc57-Te5R from parental strain Sc57. We detected 15 CDS
      inactivating mutations, and found that 3 of them affected genes coding
      mitochondrial ribosomal proteins (MRPL44 and NAM9) and mitochondrial ribosomal
      biogenesis (GEP3) pointing out to alteration of mitochondrial ribosome as main
      determinant of tellurite resistance.

PMID- 30104662
TI  - Electromagnetic wave absorption and structural properties of wide-band absorber
      made of graphene-printed glass-fibre composite.
AB  - Lightweight composites combining electromagnetic wave absorption and excellent
      mechanical properties are required in spacecraft and aircraft. A one- dimensional
      metamaterial absorber consisting of a stack of glass fibre/epoxy layers and
      graphene nanoplatelets/epoxy films was proposed and fabricated through a facile
      air-spraying based printing technology and a liquid resin infusion method. The
      production process allows an optimum dispersion of graphene nanoplatelets,
      promoting adhesion and mechanical integration of the glass fibre/epoxy layers
      with the graphene nanoplatelets/epoxy films. According to experimental results,
      the proposed wide-band absorber provides a reflection coefficient lower than -10
      dB in the range 8.5-16.7 GHz and an improvement of flexural modulus of more than
      15%, with a total thickness of ~1 mm. Outstanding electromagnetic wave absorption
      and mechanical performance make the proposed absorber more competitive in
      aeronautical and aerospace applications.

PMID- 30104661
TI  - Terminal uridylyltransferases target RNA viruses as part of the innate immune
      system.
AB  - RNA viruses are a major threat to animals and plants. RNA interference (RNAi) and
      the interferon response provide innate antiviral defense against RNA viruses.
      Here, we performed a large-scale screen using Caenorhabditis elegans and its
      natural pathogen the Orsay virus (OrV), and we identified cde-1 as important for
      antiviral defense. CDE-1 is a homolog of the mammalian TUT4 and TUT7 terminal
      uridylyltransferases (collectively called TUT4(7)); its catalytic activity is
      required for its antiviral function. CDE-1 uridylates the 3' end of the OrV RNA
      genome and promotes its degradation in a manner independent of the RNAi pathway.
      Likewise, TUT4(7) enzymes uridylate influenza A virus (IAV) mRNAs in mammalian
      cells. Deletion of TUT4(7) leads to increased IAV mRNA and protein levels.
      Collectively, these data implicate 3'-terminal uridylation of viral RNAs as a
      conserved antiviral defense mechanism.

PMID- 30104664
TI  - DAF-21/Hsp90 is required for C. elegans longevity by ensuring DAF-16/FOXO isoform
      A function.
AB  - The FOXO transcription factor family is a conserved regulator of longevity and
      the downstream target of insulin/insulin-like signaling. In Caenorhabditis
      elegans, the FOXO ortholog DAF-16A and D/F isoforms extend lifespan in daf-2
      insulin-like receptor mutants. Here we identify the DAF-21/Hsp90 chaperone as a
      longevity regulator. We find that reducing DAF-21 capacity by daf-21(RNAi)
      initiated either at the beginning or at the end of larval development shortens
      wild-type lifespan. daf-21 knockdown employed from the beginning of larval
      development also decreases longevity of daf-2 mutant and daf-2 silenced
      nematodes. daf-16 loss-of-function mitigates the lifespan shortening effect of
      daf-21 silencing. We demonstrate that DAF-21 specifically promotes daf-2 and heat
      shock induced nuclear translocation of DAF-16A as well as the induction of DAF
      16A-specific mRNAs, without affecting DAF-16D/F localization and transcriptional
      function. DAF-21 is dispensable for the stability and nuclear import of DAF-16A,
      excluding a chaperone-client interaction and suggesting that DAF-21 regulates DAF
      16A activation upstream of its cellular traffic. Finally, we show a selective
      requirement for DAF-21 to extend lifespan of DAF-16A, but not DAF-16D/F,
      transgenic daf-2 mutant strains. Our findings indicate a spatiotemporal
      determination of multiple DAF-21 roles in fertility, development and longevity
      and reveal an isoform-specific regulation of DAF-16 activity.

PMID- 30104663
TI  - High efficiency planar-type perovskite solar cells with negligible hysteresis
      using EDTA-complexed SnO2.
AB  - Even though the mesoporous-type perovskite solar cell (PSC) is known for high
      efficiency, its planar-type counterpart exhibits lower efficiency and hysteretic
      response. Herein, we report success in suppressing hysteresis and record
      efficiency for planar-type devices using EDTA-complexed tin oxide (SnO2) electron
      transport layer. The Fermi level of EDTA-complexed SnO2 is better matched with
      the conduction band of perovskite, leading to high open-circuit voltage. Its
      electron mobility is about three times larger than that of the SnO2. The record
      power conversion efficiency of planar-type PSCs with EDTA-complexed SnO2
      increases to 21.60% (certified at 21.52% by Newport) with negligible hysteresis.
      Meanwhile, the low-temperature processed EDTA-complexed SnO2 enables 18.28%
      efficiency for a flexible device. Moreover, the unsealed PSCs with EDTA-complexed
      SnO2 degrade only by 8% exposed in an ambient atmosphere after 2880 h, and only
      by 14% after 120 h under irradiation at 100 mW cm-2.

PMID- 30104665
TI  - Emergence of winner-takes-all connectivity paths in random nanowire networks.
AB  - Nanowire networks are promising memristive architectures for neuromorphic
      applications due to their connectivity and neurosynaptic-like behaviours. Here,
      we demonstrate a self-similar scaling of the conductance of networks and the
      junctions that comprise them. We show this behavior is an emergent property of
      any junction-dominated network. A particular class of junctions naturally leads
      to the emergence of conductance plateaus and a "winner-takes-all" conducting path
      that spans the entire network, and which we show corresponds to the lowest-energy
      connectivity path. The memory stored in the conductance state is distributed
      across the network but encoded in specific connectivity pathways, similar to that
      found in biological systems. These results are expected to have important
      implications for development of neuromorphic devices based on reservoir
      computing.

PMID- 30104666
TI  - Distribution of oxidized DJ-1 in Parkinson's disease-related sites in the brain
      and in the peripheral tissues: effects of aging and a neurotoxin.
AB  - DJ-1 plays an important role in antioxidant defenses, and a reactive cysteine at
      position 106 (Cys106) of DJ-1, a critical residue of its biological function, is
      oxidized under oxidative stress. DJ-1 oxidation has been reported in patients
      with Parkinson's disease (PD), but the relationship between DJ-1 oxidation and PD
      is still unclear. In the present study using specific antibody for Cys106
      oxidized DJ-1 (oxDJ-1), we analyzed oxDJ-1 levels in the brain and peripheral
      tissues in young and aged mice and in a mouse model of PD induced using 1-methyl
      4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). OxDJ-1 levels in the brain, heart,
      and skeletal muscle were high compared with other tissues. In the brain, oxDJ-1
      was detected in PD-related brain sites such as the substantia nigra (SN) of the
      midbrain, olfactory bulb (OB), and striatum. In aged wild-type mice, oxDJ-1
      levels in the OB, striatum, and heart tended to decrease, while those in the
      skeletal muscle increased significantly. Expression of dopamine-metabolizing
      enzymes significantly increased in the SN and OB of aged DJ-1-/- mice,
      accompanied by a complementary increase in glutathione peroxidase 1. MPTP
      treatment concordantly changed oxDJ-1 levels in PD-related brain sites and heart.
      These results indicate that the effects of physiological metabolism, aging, and
      neurotoxin change oxDJ-1 levels in PD-related brain sites, heart, and skeletal
      muscle where mitochondrial load is high, suggesting a substantial role of DJ-1 in
      antioxidant defenses and/or dopamine metabolism in these tissues.

PMID- 30104668
TI  - Biomaterial-assisted targeted modulation of immune cells in cancer treatment.
AB  - The past decade has witnessed the accelerating development of immunotherapies for
      cancer treatment. Immune checkpoint blockade therapies and chimeric antigen
      receptor (CAR)-T cell therapies have demonstrated clinical efficacy against a
      variety of cancers. However, issues including life-threatening off-target side
      effects, long processing times, limited patient responses and high cost still
      limit the clinical utility of cancer immunotherapies. Biomaterial carriers of
      these therapies, though, enable one to troubleshoot the delivery issues, amplify
      immunomodulatory effects, integrate the synergistic effect of different molecules
      and, more importantly, home and manipulate immune cells in vivo. In this Review,
      we will analyse thus-far developed immunomaterials for targeted modulation of
      dendritic cells, T cells, tumour-associated macrophages, myeloid-derived
      suppressor cells, B cells and natural killer cells, and summarize the promises
      and challenges of cell-targeted immunomodulation for cancer treatment.

PMID- 30104667
TI  - The landscape of the A-to-I RNA editome from 462 human genomes.
AB  - A-to-I editing, as a post-transcriptional modification process mediated by ADAR,
      plays a crucial role in many biological processes in metazoans. However, how and
      to what extent A-to-I editing diversifies and shapes population diversity at the
      RNA level are largely unknown. Here, we used 462 mRNA-sequencing samples from
      five populations of the Geuvadis Project and identified 16,518 A-to-I editing
      sites, with false detection rate of 1.03%. These sites form the landscape of the
      RNA editome of the human genome. By exploring RNA editing within and between
      populations, we revealed the geographic restriction of rare editing sites and
      population-specific patterns of edQTL editing sites. Moreover, we showed that RNA
      editing can be used to characterize the subtle but substantial diversity between
      different populations, especially those from different continents. Taken
      together, our results demonstrated that the nature and structure of populations
      at the RNA level are illustrated well by RNA editing, which provides insights
      into the process of how A-to-I editing shapes population diversity at the
      transcriptomic level. Our work will facilitate the understanding of the landscape
      of the RNA editome at the population scale and will be helpful for interpreting
      differences in the distribution and prevalence of disease among individuals and
      across populations.

PMID- 30104669
TI  - Two-dimensional itinerant ferromagnetism in atomically thin Fe3GeTe2.
AB  - Discoveries of intrinsic two-dimensional (2D) ferromagnetism in van der Waals
      (vdW) crystals provide an interesting arena for studying fundamental 2D magnetism
      and devices that employ localized spins1-4. However, an exfoliable vdW material
      that exhibits intrinsic 2D itinerant magnetism remains elusive. Here we
      demonstrate that Fe3GeTe2 (FGT), an exfoliable vdW magnet, exhibits robust 2D
      ferromagnetism with strong perpendicular anisotropy when thinned down to a
      monolayer. Layer-number-dependent studies reveal a crossover from 3D to 2D Ising
      ferromagnetism for thicknesses less than 4 nm (five layers), accompanied by a
      fast drop of the Curie temperature (TC) from 207 K to 130 K in the monolayer. For
      FGT flakes thicker than ~15 nm, a distinct magnetic behaviour emerges in an
      intermediate temperature range, which we show is due to the formation of
      labyrinthine domain patterns. Our work introduces an atomically thin
      ferromagnetic metal that could be useful for the study of controllable 2D
      itinerant ferromagnetism and for engineering spintronic vdW heterostructures5.

PMID- 30104670
TI  - The activity and discussion points of #Circumcision through Twitter; a
      microblogging platform.
AB  - OBJECTIVES: Our objective was to elucidate the discussion points of circumcision
      on social media (SoMe) by looking at the Twitter activity. MATERIAL AND METHODS:
      Twitter searched for #circumcision hashtag via www.tweetarchivist.com ,
      www.twitonomy.com , www.symplur.com . Total tweet numbers, most influencers, top
      users were documented. Tweets including female circumcision were excluded. The
      contents of the tweets were classified into four subgroups (medical, religious,
      social, and political) by two independent reviewers. All kinds of tweet
      activities were statistically analyzed. RESULTS: A total of 9795 users generated
      15,989 tweets about circumcision in a 1 month period. Mean daily tweet activity
      was 532 for #circumcision. The content analysis revealed that 2224 (15.8%)
      medical, 1133 (8.0%) religious, 323 (2.2%) social and 10,470 (74.0%) political
      tweets have been sent out by the users. Contributors originated from 174
      countries from 6 continents. Media organizations were accounted for 52% of the
      top 25 influencers in circumcision hashtag. The most common hashtags accompanying
      #circumcision were #HIV (4.9%), #babiesgotherpes (3.3%), #muslim (1.8%),
      #malegenitalmutilation (1.6%) respectively. CONCLUSIONS: There is an increasing
      discussion about circumcision through SoMe . Our results provided that the
      discussion points are mostly driven by the media and the activists. The political
      tweets have been found to be the center of the discussion. SoMe usage should be
      increased by medical professionals for true information of the public.

PMID- 30104671
TI  - Prevalence and correlates of erectile dysfunction in type 2 diabetic men: a
      population-based cross-sectional study in Chinese men.
AB  - The aim of this study was to estimate the prevalence and correlates of erectile
      dysfunction (ED) in a sample of Chinese type 2 diabetic men. Between October 2016
      and April 2017, male patients with type 2 diabetes mellitus treated in our
      diabetes outpatient clinic were recruited in this study. The participants were
      asked to complete a short version of the International Index of Erectile Function
      (IIEF-5), which was a validated and self-administered questionnaire for the
      diagnosis and grading of ED severity. All patients screened for erectile function
      also underwent detailed physical examination, and interviewed for demographic and
      medical history. A total of 550 men were recruited in this study, of whom 20
      patients were excluded and 35 did not complete all scheduled study procedures,
      leaving 495 patients in the final analysis. As determined by IIEF-5 score, 318
      (64.2%) patients had ED. Among the 318 patients with ED, mild, mild-to-moderate,
      moderate, and severe were 37 (11.6%), 65 (20.4%), 95 (29.9%), and 121 (38.1%),
      respectively. The prevalence of ED in patients with high education, secondary
      education, and less than secondary education were 83.3%, 60.2%, and 35.4%,
      respectively (P < 0.0001). The prevalence of ED was 64.2% in Chinese type 2
      diabetic men. Increased age, longer duration of diabetes mellitus, and worse
      glycemic control may promote the progression of ED among Chinese type 2 diabetic
      men. We also found that the higher education levels may increase the risk of ED
      in men with type 2 diabetes mellitus.

PMID- 30104672
TI  - Elicitors Derived from Hazel (Corylus avellana L.) Cell Suspension Culture
      Enhance Growth and Paclitaxel Production of Epicoccum nigrum.
AB  - The microbial fermentation is considered as the potential source for large-scale
      production of paclitaxel. Since co-cultivation/mixed fermentation strategy has
      been reported as a yield enhancement strategy for paclitaxel production,
      investigation of fungal endophyte response to plant culture medium, plant cell
      extract (CE) and medium filtrate (MF) of plant cell suspension culture in terms
      of growth and paclitaxel production is interesting. In this study, 35 endophytic
      fungi were isolated from Taxus baccata and Corylus avellana grown in Iran. The
      analysis of high-performance liquid chromatography and mass spectrometry showed
      that one isolate (YEF2) produced paclitaxel. The isolate YEF2 was identified as
      Epicoccum nigrum by sequencing of ITS1-5.8S-ITS2 rDNA region and actin gene. YEF2
      was slow-growing in Murashige and Skoog medium, but the synergistic interaction
      of gibberellic acid (GA3) and CE of C. avellana enhanced the growth of YEF2. The
      highest total yield of paclitaxel (314.7 ug/l; 11.5-folds) of E. nigrum strain
      YEF2 was obtained by using 28% (v/v) filter sterilized CE of C. avellana and 2 ug
      ml-1 GA3 that was significantly higher than the control. In this study, the
      effects of the plant cell extract on growth and paclitaxel production of
      paclitaxel producing endophytic fungus were studied for the first time.

PMID- 30104674
TI  - Post-eruptive mobility of lithium in volcanic rocks.
AB  - To reflect magmatic conditions, volcanic rocks must retain their compositions
      through eruption and post-eruptive cooling. Mostly, this is the case. However,
      welded ignimbrites from the Yellowstone-Snake River Plain magmatic province
      reveal systematic modification of the lithium (Li) inventory by post-eruptive
      processes. Here we show that phenocrysts from slowly cooled microcrystalline
      ignimbrite interiors consistently have significantly more Li than their rapidly
      quenched, glassy, counterparts. The strong association with host lithology and
      the invariance of other trace elements indicate that Li remains mobile long after
      eruption and readily passes into phenocrysts via diffusion as groundmass
      crystallisation increases the Li contents of the last remaining melts. Li
      isotopic measurements reveal that this diffusion during cooling combined with
      efficient degassing on the surface may significantly affect the Li inventory and
      isotopic compositions of volcanic rocks. Utilisation of Li for petrogenetic
      studies is therefore crucially dependent on the ability to 'see through' such
      post-eruptive processes.

PMID- 30104673
TI  - Pan-cancer deconvolution of tumour composition using DNA methylation.
AB  - The nature and extent of immune cell infiltration into solid tumours are key
      determinants of therapeutic response. Here, using a DNA methylation-based
      approach to tumour cell fraction deconvolution, we report the integrated analysis
      of tumour composition and genomics across a wide spectrum of solid cancers.
      Initially studying head and neck squamous cell carcinoma, we identify two
      distinct tumour subgroups: 'immune hot' and 'immune cold', which display
      differing prognosis, mutation burden, cytokine signalling, cytolytic activity and
      oncogenic driver events. We demonstrate the existence of such tumour subgroups
      pan-cancer, link clonal-neoantigen burden to cytotoxic T-lymphocyte infiltration,
      and show that transcriptional signatures of hot tumours are selectively engaged
      in immunotherapy responders. We also find that treatment-naive hot tumours are
      markedly enriched for known immune-resistance genomic alterations, potentially
      explaining the heterogeneity of immunotherapy response and prognosis seen within
      this group. Finally, we define a catalogue of mediators of active antitumour
      immunity, deriving candidate biomarkers and potential targets for precision
      immunotherapy.

PMID- 30104675
TI  - Climatic modulation of surface acidification rates through summertime wind
      forcing in the Southern Ocean.
AB  - While the effects of the Southern Annular Mode (SAM), a dominant climate
      variability mode in the Southern Ocean, on ocean acidification have been examined
      using models, no consensus has been reached. Using observational data from south
      of Tasmania, we show that during a period with positive SAM trends, surface water
      pH and aragonite saturation state at 60 degrees -55 degrees  S (Antarctic Zone)
      decrease in austral summer at rates faster than those predicted from atmospheric
      CO2 increase alone, whereas an opposite pattern is observed at 50 degrees -45
      degrees  S (Subantarctic Zone). Together with other processes, the enhanced
      acidification at 60 degrees -55 degrees  S may be attributed to increased
      westerly winds that bring in more "acidified" waters from the higher latitudes
      via enhanced meridional Ekman transport and from the subsurface via increased
      vertical mixing. Our observations support climatic modulation of ocean
      acidification superimposed on the effect of increasing atmospheric CO2.

PMID- 30104676
TI  - High-resolution synchrotron-based X-ray microtomography as a tool to unveil the
      three-dimensional neuronal architecture of the brain.
AB  - The assessment of neuronal number, spatial organization and connectivity is
      fundamental for a complete understanding of brain function. However, the
      evaluation of the three-dimensional (3D) brain cytoarchitecture at cellular
      resolution persists as a great challenge in the field of neuroscience. In this
      context, X-ray microtomography has shown to be a valuable non-destructive tool
      for imaging a broad range of samples, from dense materials to soft biological
      specimens, arisen as a new method for deciphering the cytoarchitecture and
      connectivity of the brain. In this work we present a method for imaging whole
      neurons in the brain, combining synchrotron-based X-ray microtomography with the
      Golgi-Cox mercury-based impregnation protocol. In contrast to optical 3D
      techniques, the approach shown here does neither require tissue slicing or
      clearing, and allows the investigation of several cells within a 3D region of the
      brain.

PMID- 30104677
TI  - Early-onset liver cancer in South America associates with low hepatitis B virus
      DNA burden.
AB  - In Peru, hepatocellular carcinoma (HCC) arises in young non-cirrhotic patients.
      Hepatitis B virus (HBV) is suspected to be the prominent etiological agent. We
      thus performed a comprehensive molecular study of HBV infection in 65 Peruvian
      HCC patients. Only 51% were considered as persistently infected at the onset. HBV
      DNA was found by PCR in the tumor and/or matched non-tumor liver tissues in more
      than 80% of cases (n = 53/65). HBV DNA was significantly more abundant in livers
      of younger patients than in those of the older ones. We consistently observed low
      viral DNA burden (0.1-6.5 copies for 100 cells), with viral genomes in younger
      patients displaying higher proportion of mutations at di-pyrimidines (TpT and
      CpC, P = 0.006). A drastic activation of multiple DNA repair pathways in tumors
      of younger patients was observed. Our observations clearly challenge the current
      vision that associates high HBV DNA load with earlier tumor development. We
      concluded that in Peru, and maybe in other populations with Americas' indigenous
      ancestry, HBV-associated liver tumorigenesis might differ significantly from that
      generally observed in the rest of the world. Procedures used to screen for HCC
      development in subjects at risk should be adapted to the local situation.

PMID- 30104679
TI  - Self-organization of active particles by quorum sensing rules.
AB  - Many microorganisms regulate their behaviour according to the density of
      neighbours. Such quorum sensing is important for the communication and
      organisation within bacterial populations. In contrast to living systems, where
      quorum sensing is determined by biochemical processes, the behaviour of synthetic
      active particles can be controlled by external fields. Accordingly they allow to
      investigate how variations of a density-dependent particle response affect their
      self-organisation. Here we experimentally and numerically demonstrate this
      concept using a suspension of light-activated active particles whose motility is
      individually controlled by an external feedback-loop, realised by a particle
      detection algorithm and a scanning laser system. Depending on how the particles'
      motility varies with the density of neighbours, the system self-organises into
      aggregates with different size, density and shape. Since the individual
      particles' response to their environment is almost freely programmable, this
      allows for detailed insights on how communication between motile particles
      affects their collective properties.

PMID- 30104681
TI  - i-GONAD (improved genome-editing via oviductal nucleic acids delivery), a
      convenient in vivo tool to produce genome-edited rats.
AB  - Zygote-microinjection or in vitro electroporation of isolated zygotes are now
      widely used methods to produce genome-edited mice. However, these technologies
      require laborious and time-consuming ex vivo handling of fertilized eggs,
      including zygote isolation, gene delivery into zygotes and embryo transfer into
      recipients. We recently developed an alternative method called improved genome
      editing via oviductal nucleic acids delivery (i-GONAD), which does not require
      the above-mentioned ex vivo handing of zygotes, but instead involves
      intraoviductal instillation of genome-editing components, Cas9 protein and
      synthetic gRNAs, into the oviducts of pregnant females at the late 1-cell embryo
      stage under a dissecting microscope and subsequent electroporation. With this
      method, we succeeded in generating genome-edited mice at relatively high
      efficiencies (for example, knockout alleles were produced at ~97% efficiency).
      Here, we extended this improved technology to rats, and found that i-GONAD can
      create genome-edited rats in various strains, including Sprague Dawley and Lewis,
      and F1 hybrids (between Sprague Dawley and Brown Norway), with efficiencies of
      ~62% for indel mutations and ~9% for knock-ins. Thus, i-GONAD will be especially
      useful for the production of genome-edited rats in small laboratories where
      expensive micromanipulator systems and highly skilled personnel for embryo
      manipulation are unavailable.

PMID- 30104678
TI  - PARP2 mediates branched poly ADP-ribosylation in response to DNA damage.
AB  - Poly(ADP-ribosyl)ation (PARylation) is a posttranslational modification involved
      in multiple biological processes, including DNA damage repair. This modification
      is catalyzed by poly(ADP-ribose) polymerase (PARP) family of enzymes. PARylation
      is composed of both linear and branched polymers of poly(ADP-ribose) (PAR).
      However, the biochemical mechanism of polymerization and biological functions of
      branched PAR chains are elusive. Here we show that PARP2 is preferentially
      activated by PAR and subsequently catalyzes branched PAR chain synthesis.
      Notably, the direct binding to PAR by the N-terminus of PARP2 promotes the
      enzymatic activity of PARP2 toward the branched PAR chain synthesis. Moreover,
      the PBZ domain of APLF recognizes the branched PAR chain and regulates chromatin
      remodeling to DNA damage response. This unique feature of PAR-dependent PARP2
      activation and subsequent PARylation mediates the participation of PARP2 in DNA
      damage repair. Thus, our results reveal an important molecular mechanism of
      branched PAR synthesis and a key biological function of branched PARylation.

PMID- 30104680
TI  - Assessment of physical inactivity and locomotor dysfunction in adults with visual
      impairment.
AB  - To evaluate the association between vision-related quality of life (QoL),
      physical inactivity, and locomotor dysfunction in subjects with visual
      impairment.This cross-sectional study included 215 visually impaired subjects
      recruited from six ophthalmology departments in Japan. The physical inactivity
      and locomotor dysfunction associated with their visual impairment was
      investigated. The physical activity level was assessed using the short form of
      the International Physical Activity Questionnaire and classified as high,
      moderate, or low. Locomotor function was evaluated with the Geriatric Locomotive
      Function Scale. Vision-related QoL was evaluated using the 25-item National Eye
      Institute Visual Function Questionnaire. Background data, including for age, sex,
      best-corrected visual acuity for each eye, causative eye diseases, systemic
      comorbidities, and body mass index, were also collected.The average patient age
      was 69.6 (range, 20-93 years; standard deviation, 14.5 years) and 118 patients
      (54.9%) were men. Multivariate analysis showed that vision-related QoL and best
      corrected visual acuity in the worse eye were significantly associated with
      physical inactivity and that vision-related QoL, female sex, age, and presence of
      systemic comorbidity were significantly associated with locomotor dysfunction.
      Vision-related quality of life is associated with physical inactivity and
      locomotor dysfunction.

PMID- 30104683
TI  - The role of Chinese Milk Vetch as cover crop in complex soil nitrogen dynamics in
      rice rotation system of South China.
AB  - The effect of Chinese Milk Vetch (CMV) residues as a cover crop on the
      performance of rice plants and nitrogen mobilization and mineralization in paddy
      soil was evaluated in a pot-culture experiment. Three treatments were included in
      the trial, i.e. without exogenous-N (Control or CK), urea fertilizer as the sole
      N-source (N) and urea plus CMV (NM). The results revealed higher amounts of total
      N, inorganic-N, acid hydrolysable-N and non-acid hydrolysable-N in the soil under
      NM, followed by N and CK treatments at tillering, booting and maturity stages of
      rice. A similar trend was observed for various soil ammonia oxidizing bacteria,
      aerobic and anaerobic bacteria. Correlation coefficients exhibited a negative
      correlation of residual exogenous-15N with only amino acid nitrogen (P < 0.01).
      Moreover, low abundance of the key functional gene amoA in rice was found in CK
      treatment. From the results it can be concluded that the nitrogen from organic
      source can improve the availability of total-N, inorganic-N and NH4 in the soil,
      especially at the later stages of rice growth.

PMID- 30104682
TI  - Effect of maternal pre-pregnancy underweight and average gestational weight gain
      on physical growth and intellectual development of early school-aged children.
AB  - The aim of this study was to assess the effect of low maternal weight at pre
      pregnancy and the average gestational weight gain on undernourished children and
      their intellectual development. From October 2012 to September 2013, we followed
      1744 offspring of women who participated in a trial conducted from 2002 to 2006.
      Pregnant women recruited in the original trial could receive three prenatal
      health checks for free, at which maternal weight and height were measured. WISC
      IV was used to estimate the intellectual development of children. Weight and
      height of both pregnant women and children were measured by trained
      anthropometrists using standard procedures. Having low maternal weight at pre
      pregnancy was associated with an increased risk of undernutrition amongst
      children (underweight: OR = 2.02, 95%CI: 1.14-3.56, thinness: OR = 2.79, 95%CI:
      1.50-5.17) and a decrease in verbal comprehension index (-2.70 points, 95%CI: 
      4.95-0.44) of children. The effect of average gestational weight gain on
      occurrences of underweight children (OR = 0.08, 95%CI: 0.01-0.55) was also found.
      We identified the effect of maternal pre-pregnancy underweight on impairment of
      the separate intellectual domains (verbal comprehension index) and increasing
      occurrence of undernourished children. Average gestational weight gain was
      positively associated with a decreased prevalence of underweight children but not
      with the intellectual development of children in rural China.

PMID- 30104684
TI  - Itch suppression in mice and dogs by modulation of spinal alpha2 and alpha3GABAA
      receptors.
AB  - Chronic itch is a highly debilitating condition affecting about 10% of the
      general population. The relay of itch signals is under tight control by
      inhibitory circuits of the spinal dorsal horn, which may offer a hitherto
      unexploited therapeutic opportunity. Here, we found that specific pharmacological
      targeting of inhibitory alpha2 and alpha3GABAA receptors reduces acute
      histaminergic and non-histaminergic itch in mice. Systemic treatment with an
      alpha2/alpha3GABAA receptor selective modulator alleviates also chronic itch in a
      mouse model of atopic dermatitis and in dogs sensitized to house dust mites,
      without inducing sedation, motor dysfunction, or loss of antipruritic activity
      after prolonged treatment. Transsynaptic circuit tracing, immunofluorescence, and
      electrophysiological experiments identify spinal alpha2 and alpha3GABAA receptors
      as likely molecular targets underlying the antipruritic effect. Our results
      indicate that drugs targeting alpha2 and alpha3GABAA receptors are well-suited to
      alleviate itch, including non-histaminergic chronic itch for which currently no
      approved treatment exists.

PMID- 30104685
TI  - Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt
      lymphoma.
AB  - Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma associated with MYC
      translocation. Here, we describe drug response profiling of 42 blood cancer cell
      lines including 17 BL to 32 drugs targeting key cancer pathways and provide a
      systematic study of drug combinations in BL cell lines. Based on drug response,
      we identified cell line specific sensitivities, i.e. to venetoclax driven by BCL2
      overexpression and partitioned subsets of BL driven by response to kinase
      inhibitors. In the combination screen, including BET, BTK and PI3K inhibitors, we
      identified synergistic combinations of PI3K and BTK inhibition with drugs
      targeting Akt, mTOR, BET and doxorubicin. A detailed comparison of PI3K and BTKi
      combinations identified subtle differences, in line with convergent pathway
      activity. Most synergistic combinations were identified for the BET inhibitor
      OTX015, which showed synergistic effects for 41% of combinations including
      inhibitors of PI3K/AKT/mTOR signalling. The strongest synergy was observed for
      the combination of the CDK 2/7/9 inhibitor SNS032 and OTX015. Our data provide a
      landscape of drug combination effects in BL and suggest that targeting CDK and
      BET could provide a novel vulnerability of BL.

PMID- 30104687
TI  - Fire-induced structural changes and long-term stability of burned historical rag
      papers.
AB  - When a fire strikes libraries or archives, physical deterioration of the paper is
      so severe that its chemical properties are often regarded as less important.
      However, knowledge of the chemical changes of the papers upon nearly burning is
      necessary to design a subsequent conservation treatment. In the present study, we
      have examined a rag paper object, which partially survived a fire, and analysed
      its chemical properties by various methods. The polymeric state of cellulose, as
      well as its low-molar mass degradation products, were assessed. Comparison to an
      identical, unharmed duplicate provided a more profound understanding of the
      changes caused by the fire. Light scattering analysis revealed conformational
      changes of the cellulose molecule after high-temperature impact, and a chemical
      cross-linking was observed. In our study, we found the integrity of cellulose to
      depend on the temperature profile induced by the fire. The low thermal
      conductivity of cellulose protects the material even in close proximity to the
      burned edges.

PMID- 30104686
TI  - TNFR2 ligation in human T regulatory cells enhances IL2-induced cell
      proliferation through the non-canonical NF-kappaB pathway.
AB  - Human T regulatory cells (T regs) express high levels of TNF receptor 2 (TNFR2).
      Ligation of TNFR2 with TNF, which can recognise both TNFR1 and TNFR2, or with a
      TNFR2-selective binding molecule, DARPin 18 (D18) activates canonical NF-kappaB
      signalling, assessed by IkappaBalpha degradation, and the magnitude of the
      response correlates with the level of TNFR2 expression. RNA-seq analysis of TNF-
      or D18-treated human T regs revealed that TNFR2 ligation induces transcription of
      NFKB2 and RELB, encoding proteins that form the non-canonical NF-kappaB
      transcription factor. In combination with IL2, D18 treatment is specific for T
      regs in (1) stabilising NF-kappaB-inducing kinase protein, the activator of non
      canonical NF-kappaB signalling, (2) inducing translocation of RelB from cytosol
      to nucleus, (3) increasing cell cycle entry, and (4) increasing cell numbers.
      However, the regulatory function of the expanded T regs is unaltered. Inhibition
      of RelB nuclear translocation blocks the proliferative response. We conclude that
      ligation of TNFR2 by D18 enhances IL2-induced T regs proliferation and expansion
      in cell number through the non-canonical NF-kappaB pathway.

PMID- 30104688
TI  - Analysis of sequencing strategies and tools for taxonomic annotation: Defining
      standards for progressive metagenomics.
AB  - Metagenomics research has recently thrived due to DNA sequencing technologies
      improvement, driving the emergence of new analysis tools and the growth of
      taxonomic databases. However, there is no all-purpose strategy that can guarantee
      the best result for a given project and there are several combinations of
      software, parameters and databases that can be tested. Therefore, we performed an
      impartial comparison, using statistical measures of classification for eight
      bioinformatic tools and four taxonomic databases, defining a benchmark framework
      to evaluate each tool in a standardized context. Using in silico simulated data
      for 16S rRNA amplicons and whole metagenome shotgun data, we compared the results
      from different software and database combinations to detect biases related to
      algorithms or database annotation. Using our benchmark framework, researchers can
      define cut-off values to evaluate the expected error rate and coverage for their
      results, regardless the score used by each software. A quick guide to select the
      best tool, all datasets and scripts to reproduce our results and benchmark any
      new method are available at https://github.com/Ales-ibt/Metagenomic-benchmark .
      Finally, we stress out the importance of gold standards, database curation and
      manual inspection of taxonomic profiling results, for a better and more accurate
      microbial diversity description.

PMID- 30104690
TI  - Targeting mechanisms of tailed bacteriophages.
AB  - Phages differ substantially in the bacterial hosts that they infect. Their host
      range is determined by the specific structures that they use to target bacterial
      cells. Tailed phages use a broad range of receptor-binding proteins, such as tail
      fibres, tail spikes and the central tail spike, to target their cognate bacterial
      cell surface receptors. Recent technical advances and new structure-function
      insights have begun to unravel the molecular mechanisms and temporal dynamics
      that govern these interactions. Here, we review the current understanding of the
      targeting machinery and mechanisms of tailed phages. These new insights and
      approaches pave the way for the application of phages in medicine and
      biotechnology and enable deeper understanding of their ecology and evolution.

PMID- 30104691
TI  - Mutual Interaction between Plasma Characteristics and Liquid Properties in AC
      driven Pin-to-Liquid Discharge.
AB  - This study investigated the mutual interaction between the plasma and plasma
      treated water (PTW). Many works have shown that the plasma treatment decreases
      the pH of PTW due to nitric oxide electrolyte ion but the interactions between
      PTW and the plasma are still largely unknown. We investigated the effect of PTW
      on a plasma as well as the effect of a plasma on PTW using a pin-to-liquid
      discharge system. It is found that PTW affects not only the chemical properties
      but also the physical properties of the plasma such as breakdown voltage and
      concentration of plasma column. The decrease of the liquid surface tension of PTW
      due to nitric oxide electrolyte ion from the plasma results in the increase of
      plasma current onto the surface of PTW and vice versa. The feedback process will
      be continued until the transition from normal discharge to abnormal discharge.
      These results can be basic data for the development of plasma sources to treat
      liquids.

PMID- 30104689
TI  - A Low-Cost Non-explosive Synthesis of Graphene Oxide for Scalable Applications.
AB  - A low cost, non-explosive process for the synthesis of graphene oxide (GO) is
      demonstrated. Using suitable choice of reaction parameters including temperature
      and time, this recipe does not require expensive membranes for filtration of
      carbonaceous and metallic residues. A pre-cooling protocol is introduced to
      control the explosive nature of the highly exothermic reactions during the
      oxidation process. This alleviates the requirement for expensive membranes and
      completely eliminates the explosive nature of intermediate reaction steps when
      compared to existing methods. High quality of the synthesized GO is corroborated
      using a host of characterization techniques including X-ray diffraction, optical
      spectroscopy, X-ray photoemission spectroscopy and current-voltage
      characteristics. Simple reduction protocol using ultra-violet light is
      demonstrated for potential application in the area of photovoltaics. Using
      different reduction protocols together with the proposed inexpensive method,
      reduced GO samples with tunable conductance over a wide range of values is
      demonstrated. Density functional theory is employed to understand the structure
      of GO. We anticipate that this scalable approach will catalyze large scale
      applications of GO.

PMID- 30104692
TI  - A Novel Frequency Selectivity Approach Based on Travelling Wave Propagation in
      Mechanoluminescence Basilar Membrane for Artificial Cochlea.
AB  - This study presents the initial assessment for a new approach to frequency
      selectivity aimed at mimicking the function of the basilar membrane within the
      human cochlea. The term cochlea tonotopy refers to the passive frequency
      selectivity and a transformation from the acoustic wave into a frequency signal
      assisted by the hair cells in the organ of Corti. While high-frequency sound
      waves vibrate near the base of the cochlea (near the oval windows), low-frequency
      waves vibrate near the apex (at the maximum distance from the base), which
      suggests the existence of continuous frequency selectivity. Over the past few
      decades, frequency selectivity using artificial membranes has been utilized in
      acoustic transducers by mimicking cochlea tonotopy using cantilever-beam arrays
      with defined physical parameters such as length and thickness. Unlike the
      conventional cantilever-beam array type, the travelling wave propagation based
      mechanoluminescence (ML) membrane made of ZnS:Cu- polydimethylsiloxane (ZnS:Cu
      PDMS) composite that we describe here provides new frequency selectivity more
      similar to that demonstrated by the human membrane. Here, we explored the
      potential of the ML membrane to deliver new frequency selectivity by using a non
      contact image sensor to measure visualized frequencies. We report that the ML
      basilar membrane can provide effective visualization of the distribution of
      strain rate associated with the position of maximal amplitude of the travelling
      wave.

PMID- 30104695
TI  - Reply to 'Economic comments on proposal for a novel cancer drug pricing model'.

PMID- 30104693
TI  - Extensive genomic diversity among Mycobacterium marinum strains revealed by whole
      genome sequencing.
AB  - Mycobacterium marinum is the causative agent for the tuberculosis-like disease
      mycobacteriosis in fish and skin lesions in humans. Ubiquitous in its
      geographical distribution, M. marinum is known to occupy diverse fish as hosts.
      However, information about its genomic diversity is limited. Here, we provide the
      genome sequences for 15 M. marinum strains isolated from infected humans and
      fish. Comparative genomic analysis of these and four available genomes of the M.
      marinum strains M, E11, MB2 and Europe reveal high genomic diversity among the
      strains, leading to the conclusion that M. marinum should be divided into two
      different clusters, the "M"- and the "Aronson"-type. We suggest that these two
      clusters should be considered to represent two M. marinum subspecies. Our data
      also show that the M. marinum pan-genome for both groups is open and expanding
      and we provide data showing high number of mutational hotspots in M. marinum
      relative to other mycobacteria such as Mycobacterium tuberculosis. This high
      genomic diversity might be related to the ability of M. marinum to occupy
      different ecological niches.

PMID- 30104694
TI  - Strong negative nonlinear friction from induced two-phonon processes in
      vibrational systems.
AB  - Self-sustained vibrations in systems ranging from lasers to clocks to biological
      systems are often associated with the coefficient of linear friction, which
      relates the friction force to the velocity, becoming negative. The runaway of the
      vibration amplitude is prevented by positive nonlinear friction that increases
      rapidly with the amplitude. Here we use a modulated electromechanical resonator
      to show that nonlinear friction can be made negative and sufficiently strong to
      overcome positive linear friction at large vibration amplitudes. The experiment
      involves applying a drive that simultaneously excites two phonons of the studied
      mode and a phonon of a faster decaying high-frequency mode. We study generic
      features of the oscillator dynamics with negative nonlinear friction. Remarkably,
      self-sustained vibrations of the oscillator require activation in this case.
      When, in addition, a resonant force is applied, a branch of large-amplitude
      forced vibrations can emerge, isolated from the branch of the ordinary small
      amplitude response.

PMID- 30104696
TI  - Economic comments on proposal for a novel cancer drug pricing model.

PMID- 30104697
TI  - Comparison of Radial Artery Occlusion Following Transradial Access for
      Percutaneous Coronary Intervention Using Sheath-based versus Sheathless
      Technique.
AB  - We compared the risk of radial artery occlusion (RAO) in patients undergoing
      coronary intervention with introducer sheath (SG) or without introducer sheath
      (SLG). 1251 consecutive patients, from 2 tertiary care center in Pennsylvania,
      USA, undergoing percutaneous coronary interventions (PCI) between 2008-2013
      formed the study cohort (SLG: 161 patients, SG: 1090 patients). Radial artery
      patency was assessed using plethysmography. The association between sheath use
      and RAO was assessed using unadjusted, adjusted and propensity macthed logistic
      regression analyses. Mean age: 65 years, men: 63%, diabetics: 37%. SG was
      associated with lower RAO at band removal [unadjusted (OR: 0.31, 95% CI: 0.21
      0.46), adjusted (OR: 0.10, 95% CI: 0.05-0.20) and propensity matched (OR: 0.20,
      95% CI: 0.13-0.32)], at 24 hours [unadjusted (OR: 0.20, 95% CI: 0.12-0.34),
      adjusted (OR: 0.12, 95% CI: 0.06-0.24) and propensity matched (OR: 0.13, 95% CI:
      0.07-0.25)] and 30 days [unadjusted (OR: 0.28, 95% CI: 0.14-0.54), adjusted (OR:
      0.22, 95% CI: 0.10-0.50) and propensity matched (OR: 0.18, 95% CI: 0.10-0.40)],
      compared to SLG. Sheath use during radial access for PCI is associated with less
      RAO. It is unclear if use of introducer sheath during radial access for PCI
      reduces incidence of RAO. In this prospective cohort study involving 1251
      concecutive patients undergoing PCI via radial access between 2008-2013, we
      assessed the difference in incidence of RAO between the SG (n = 1090) and the SLG
      (n = 161 patients) groups. SG group experienced lower incidence of RAO at band
      removal, 24 hours and 30 days post PCI in the unadjusted, adjusted, and
      propensity matched analyses compared to the SLG group. In conclusion sheath use
      during radial access for PCI is associated with less RAO.

PMID- 30104700
TI  - Mechanisms of signalling and biased agonism in G protein-coupled receptors.
AB  - G protein-coupled receptors (GPCRs) are the largest group of cell surface
      receptors in humans that signal in response to diverse inputs and regulate a
      plethora of cellular processes. Hence, they constitute one of the primary drug
      target classes. Progress in our understanding of GPCR dynamics, activation and
      signalling has opened new possibilities for selective drug development. A key
      advancement has been provided by the concept of biased agonism, which describes
      the ability of ligands acting at the same GPCR to elicit distinct cellular
      signalling profiles by preferentially stabilizing different active conformational
      states of the receptor. Application of this concept raises the prospect of
      'designer' biased agonists as optimized therapeutics with improved efficacy
      and/or reduced side-effect profiles. However, this application will require a
      detailed understanding of the spectrum of drug actions and a structural
      understanding of the drug-receptor interactions that drive distinct
      pharmacologies. The recent revolution in GPCR structural biology provides
      unprecedented insights into ligand binding, conformational dynamics and the
      control of signalling outcomes. These insights, together with new approaches to
      multi-dimensional analysis of drug action, are allowing refined classification of
      drugs according to their pharmacodynamic profiles, which can be linked to
      receptor structure and predictions of preclinical drug efficacy.

PMID- 30104698
TI  - IL-1beta, IL-6, TNF- alpha and CRP in Elderly Patients with Depression or
      Alzheimer's disease: Systematic Review and Meta-Analysis.
AB  - We carried out systematic review and meta-analysis to evaluate whether peripheral
      levels of pro-inflammatory markers including Interleukin-1 beta (IL-1beta),
      Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF- alpha) and C-Reactive
      Protein (CRP) are significantly higher in elderly with depression and Alzheimer's
      disease. We searched Pubmed, PsycINFO and Embase, and thirty-four relevant
      studies (2609 with Depression, 1645 with Alzheimer's disease and 14363 Controls)
      were included. Compared with controls, IL-1beta (pooled standardized mean
      difference [SMD]: 0.642; 95% confidence interval [CI]: 0.078-1.206; significant
      heterogeneity: I2 = 86.28%) and IL-6 (pooled SMD: 0.377; 95% CI: 0.156-0.598;
      significant heterogeneity: I2 = 88.75%) were significantly elevated in
      depression. There was no difference in TNF-alpha (p = 0.351) and CRP (p = 0.05)
      between those with depression and controls. Compared with controls, IL-1beta
      (pooled SMD: 1.37, 95% CI: 0.06-2.68, significant heterogeneity: I2 = 96.01%) was
      significantly elevated in Alzheimer's disease. There were no differences in IL-6
      (p = 0.138), TNF-alpha (p = 0.451) and CRP (p = 0.07) between elderly with
      Alzheimer's disease and controls. After Bonferroni adjustment, only IL-6 remained
      significantly higher in depression. Elderly with depression have higher IL-6 than
      controls, while those with Alzheimer's disease did not have higher peripheral
      inflammatory markers.

PMID- 30104699
TI  - Quantitative phase imaging unravels new insight into dynamics of mesenchymal and
      amoeboid cancer cell invasion.
AB  - Observation and analysis of cancer cell behaviour in 3D environment is essential
      for full understanding of the mechanisms of cancer cell invasion. However, label
      free imaging of live cells in 3D conditions is optically more challenging than in
      2D. Quantitative phase imaging provided by coherence controlled holographic
      microscopy produces images with enhanced information compared to ordinary light
      microscopy and, due to inherent coherence gate effect, enables observation of
      live cancer cells' activity even in scattering milieu such as the 3D collagen
      matrix. Exploiting the dynamic phase differences method, we for the first time
      describe dynamics of differences in cell mass distribution in 3D migrating
      mesenchymal and amoeboid cancer cells, and also demonstrate that certain features
      are shared by both invasion modes. We found that amoeboid fibrosarcoma cells'
      membrane blebbing is enhanced upon constriction and is also occasionally present
      in mesenchymally invading cells around constricted nuclei. Further, we
      demonstrate that both leading protrusions and leading pseudopods of invading
      fibrosarcoma cells are defined by higher cell mass density. In addition, we
      directly document bundling of collagen fibres by protrusions of mesenchymal
      fibrosarcoma cells. Thus, such a non-invasive microscopy offers a novel insight
      into cellular events during 3D invasion.

PMID- 30104701
TI  - Metabolites as regulators of insulin sensitivity and metabolism.
AB  - The cause of insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is
      not limited to impaired insulin signalling but also involves the complex
      interplay of multiple metabolic pathways. The analysis of large data sets
      generated by metabolomics and lipidomics has shed new light on the roles of
      metabolites such as lipids, amino acids and bile acids in modulating insulin
      sensitivity. Metabolites can regulate insulin sensitivity directly by modulating
      components of the insulin signalling pathway, such as insulin receptor substrates
      (IRSs) and AKT, and indirectly by altering the flux of substrates through
      multiple metabolic pathways, including lipogenesis, lipid oxidation, protein
      synthesis and degradation and hepatic gluconeogenesis. Moreover, the post
      translational modification of proteins by metabolites and lipids, including
      acetylation and palmitoylation, can alter protein function. Furthermore, the role
      of the microbiota in regulating substrate metabolism and insulin sensitivity is
      unfolding. In this Review, we discuss the emerging roles of metabolites in the
      pathogenesis of insulin resistance and T2DM. A comprehensive understanding of the
      metabolic adaptations involved in insulin resistance may enable the
      identification of novel targets for improving insulin sensitivity and preventing,
      and treating, T2DM.

PMID- 30104702
TI  - PLGA-encapsulated CpG ODN and Campylobacter jejuni lysate modulate cecal
      microbiota composition in broiler chickens experimentally challenged with C.
      jejuni.
AB  - Campylobacter jejuni is a leading bacterial cause of human gastroenteritis.
      Reducing Campylobacter numbers in the intestinal tract of chickens will minimize
      transmission to humans, thereby reducing the incidence of infection. We have
      previously shown that oral pre-treatment of chickens with C. jejuni lysate and
      Poly D, L-lactide-co-glycolide polymer nanoparticles (PLGA NPs) containing CpG
      oligodeoxynucleotide (ODN) can reduce the number of C. jejuni in infected
      chickens. In the current study, the effects of these pre-treatments on the
      composition and functional diversity of the cecal microbiota, in chickens
      experimentally infected with C. jejuni, were investigated using next-generation
      sequencing. The taxonomic composition analysis revealed a reduction in cecal
      microbial diversity and considerable changes in the taxonomic profiles of the
      microbial communities of C. jejuni-challenged chickens. On the other hand,
      irrespective of the dose, the microbiota of PLGA-encapsulated CpG ODN- and C.
      jejuni lysate-treated chickens exhibited higher microbial diversity associated
      with high abundance of members of Firmicutes and Bacteroidetes and lower numbers
      of Campylobacter than untreated-chickens. These findings suggest that oral
      administration of encapsulated CpG ODN and C. jejuni lysate can reduce
      colonization by C. jejuni by enhancing the proliferation of specific microbial
      groups. The mechanisms that mediate these changes remain, however, to be
      elucidated.

PMID- 30104703
TI  - Room temperature processed high mobility W-doped In2O3 electrodes coated via in
      line arc plasma ion plating for flexible OLEDs and quantum dots LEDs.
AB  - We fabricated W-doped In2O3 (IWO) films at room temperature on a flexible PET
      substrate using an in-line arc plasma ion plating system for application as
      flexible transparent conducting electrodes (FTCEs) in flexible organic light
      emitting diodes (OLEDs) and quantum dots light emitting diodes (QDLEDs). Due to
      the high-energy flux of the sublimated ions generated from the plasma region, the
      IWO films showed a well-developed crystalline structure with a low sheet
      resistance of 36.39 Ohm/square and an optical transmittance of 94.6% even though
      they were prepared at room temperature. The low sheet resistance of the IWO film
      processed at room temperature is attributed to the high mobility (59 cm2/V-s) in
      the well-developed crystalline structure of the ion-plated IWO film and screening
      effect of W dopants. In addition, the better adhesion of the ion-plated IWO film
      on the PET substrate led to small critical outer and inner bending radii of 6 and
      3 mm, respectively, against substrate bending. Due to the low sheet resistance,
      high optical transmittance, better crystallinity, better adhesion, and
      outstanding flexibility of the ion-plated IWO films, the flexible OLEDs and
      QDLEDs with the IWO electrodes showed better performances than flexible OLEDs and
      QDLEDs with sputtered flexible ITO anodes. This indicates that in-line arc plasma
      ion plating is a promising large area coating technique to realize room
      temperature processed high-quality FTCEs for flexible OLEDs and QDLEDs.

PMID- 30104704
TI  - Post-Deposition Wetting and Instabilities in Organic Thin Films by Supersonic
      Molecular Beam Deposition.
AB  - We discuss the formation and post-deposition instability of nanodrop-like
      structures in thin films of PDIF-CN2 (a perylene derivative) deposited via
      supersonic molecular beam deposition technique on highly hydrophobic substrates
      at room temperature. The role of the deposition rate on the characteristic
      lengths of the organic nanodrops has been investigated by a systematic analysis
      of atomic force microscope images of the thin films and through the use of the
      height-height correlation function. The nanodrops appear to be a metastable
      configuration for the freshly-deposited films. For this reason, post-deposition
      wetting effect has been examined with unprecedented accuracy throughout a year of
      experimental observations. The observed time scales, from few hours to months,
      are related to the growth rate, and characterize the thin films morphological
      reordering from three-dimensional nanodrops to a well-connected terraced film.
      While the interplay between adhesion and cohesion energies favors the formation
      of 3D-mounted structures during the growth, wetting phenomenon following the
      switching off of the molecular flux is found to be driven by an instability. A
      slow rate downhill process survives at the molecular flux shutdown and it is
      accompanied and maybe favored by the formation of a precursor layer composed of
      more lying molecules. These results are supported by simulations based on a non
      linear stochastic model. The instability has been simulated, for both the growth
      and the post-growth evolution. To better reproduce the experimental data it is
      needed to introduce a surface equalizer term characterized by a relaxation time
      taking into account the presence of a local mechanism of molecular correlation.

PMID- 30104705
TI  - Cardiomyocytes Derived from Human CardiopoieticAmniotic Fluids.
AB  - Human amniotic fluid (hAF) cells share characteristics of both embryonic and
      adult stem cells. They proliferate rapidly and can differentiate into cells of
      all embryonic germ layers but do not form teratomas. Embryoid-bodies obtained
      from hAF have cardiac differentiation potential, but terminal differentiation to
      cardiomyocytes (CMs) has not yet been described. Our purpose was to promote
      cardiac differentiation in hAFcells. Cells were exposed to inducing factors for
      up to 15 days. Only the subset of hAF cells expressing the multipotency markers
      SSEA4, OCT4 and CD90 (CardiopoieticAF cells) responded to the differentiation
      process by increasing the expression of the cardiac transcription factors Nkx2.5
      and GATA4, sarcomeric proteins (cTnT, alpha-MHC, alpha-SA), Connexin43 and atrial
      and ventricular markers. Furthermore, differentiated cells were positive for the
      calcium pumps CACNA1C and SERCA2a, with approximately 30% of CardiopoieticAF
      derived CM-like cells responding to caffeine or adrenergic stimulation. Some
      spontaneous rare beating foci were also observed. In conclusion, we demonstrated
      that CardiopoieticAF cells might differentiate toward the cardiac lineage giving
      rise to CM-like cells characterized by several cardiac-specific molecular,
      structural, and functional properties.

PMID- 30104706
TI  - Differential expression of miRNA199b-5p as a novel biomarker for sporadic and
      hereditary parathyroid tumors.
AB  - MicroRNAs (miRNAs) are dysregulated in many tumors; however, miRNA regulation in
      parathyroid tumors remains poorly understood. To identify differentially
      expressed miRNAs between sporadic and hereditary parathyroid tumors and to
      analyze their correlation with clinicopathological features, a microarray
      containing 887 miRNAs was performed; then, the differentially expressed miRNAs
      were validated by qRT-PCR using 25 sporadic and 12 hereditary parathyroid tumors
      and 24 normal parathyroid tissue samples. A receiver operating characteristic
      curve (ROC) analysis was applied to evaluate the utility of the miRNAs for
      distinguishing parathyroid tumor types. Compared to the miRNAs in the normal
      parathyroid tissues, 10 miRNAs were differentially expressed between the sporadic
      and hereditary parathyroid tumors. Seven of these miRNAs (let-7i, miR-365, miR
      125a-3p, miR-125a-5p, miR-142-3p, miR-193b, and miR-199b-5p) were validated in
      the parathyroid tumor samples. Among these miRNAs, only miR-199b-5p was
      differentially expressed (P < 0.001); miR-199b-5p was significantly downregulated
      and negatively associated with PTH levels (gamma = -0.579, P = 0.002) in the
      sporadic tumors but was upregulated in the hereditary tumors. This miRNA showed
      67% sensitivity and 100% specificity for distinguishing sporadic and hereditary
      parathyroid tumors. These results reveal altered expression of a miRNA between
      sporadic and hereditary parathyroid tumors and the potential role of miR-199b-5p
      as a novel biomarker for distinguishing these two types of parathyroid tumors.

PMID- 30104707
TI  - The impact of non-alcoholic fatty liver disease and metabolic syndrome on the
      progression of coronary artery calcification.
AB  - It is unclear whether non-alcoholic fatty liver disease (NAFLD) is an independent
      risk factor for cardiovascular disease. We examined the independent impact of
      NAFLD on the progression of the coronary artery calcification (CAC) score, a well
      known marker of atherosclerosis progression. We examined 1,173 asymptomatic
      participants who underwent repeated CAC score measurement during routine health
      examinations. The subjects were categorised into four groups based on the
      presence (+) or absence (-) of NAFLD and metabolic syndrome (MetS). The
      progression of CAC score was defined as either incident CAC in a CAC-free
      population at baseline or an increase of >=2.5 units between the baseline and the
      final square roots of the CAC scores of participants with detectable CAC at
      baseline. CAC progression was seen in 18.6% (98/526), 28.3% (77/272), 29.1%
      (30/103) and 32.0% (87/272) of the subjects with NAFLD(-)/MetS(-), NAFLD(+)/MetS(
      ), NAFLD(-)/MetS(+) and NAFLD(+)/MetS(+), respectively. The subjects with
      NAFLD(+)/MetS(+) and NAFLD(+)/MetS(-) had a significantly higher risk of CAC
      progression than those with NAFLD(-)/MetS(-) (multivariate-adjusted odds ratio
      [OR]: 1.76; 95% confidence interval [CI]: 1.18-2.62 and multivariate-adjusted OR:
      1.53, 95% CI: 1.05-2.23, respectively). NAFLD is an independent risk factor for
      CAC progression, irrespective of the presence of MetS.

PMID- 30104708
TI  - Electronic and optical properties of heterostructures based on transition metal
      dichalcogenides and graphene-like zinc oxide.
AB  - The structural, electronic, and optical properties of heterostructures formed by
      transition metal dichalcogenides MX2 (M = Mo, W; X = S, Se) and graphene-like
      zinc oxide (ZnO) were investigated using first-principles calculations. The
      interlayer interaction in all heterostructures was characterized by van der Waals
      forces. Type-II band alignment occurs at the MoS2/ZnO and WS2/ZnO interfaces,
      together with the large built-in electric field across the interface, suggesting
      effective photogenerated-charge separation. Meanwhile, type-I band alignment
      occurs at the MoSe2/ZnO and WSe2/ZnO interfaces. Moreover, all heterostructures
      exhibit excellent optical absorption in the visible and infrared regions, which
      is vital for optical applications.

PMID- 30104710
TI  - Overexpression of miR-489 derails mammary hierarchy structure and inhibits
      HER2/neu-induced tumorigenesis.
AB  - Although it has been demonstrated that transformed progenitor cell population can
      contribute to tumor initiation, factors contributing to this malignant
      transformation are poorly known. Using in vitro and xenograft-based models,
      previous studies demonstrated that miR-489 acts as a tumor suppressor miRNA by
      targeting various oncogenic pathways. It has been demonstrated that miR-489
      directly targets HER2 and inhibits the HER2 signaling pathway; however, its role
      in mammary gland development and HER2-induced tumor initiation hasn't been
      studied. To dissect the role of miR-489, we sorted different populations of
      mammary epithelial cells and determined that miR-489 was highly expressed in
      mammary stem cells. MMTV-miR-489 mice that overexpressed miR-489 in mammary
      epithelial cells were developed and these mice exhibited an inhibition of mammary
      gland development in early ages with a specific impact on highly proliferative
      cells. Double transgenic MMTV-Her2-miR489 mice were then generated to observe how
      miR-489 overexpression affects HER2-induced tumorigenesis. miR-489 overexpression
      delayed HER2-induced tumor initiation significantly. Moreover, miR-489
      overexpression inhibited tumor growth and lung metastasis. miR-489 overexpression
      reduced mammary progenitor cell population significantly in preneoplastic mammary
      glands of MMTV-Her2 mice which showed a putative transformed population in HER2
      induced tumorigenesis. The miR-489 overexpression reduced CD49fhiCD61hi
      populations in tumors that have stem-like properties, and miR-489 overexpression
      altered the HER2 signaling pathway in mammary tumors. Altogether, these data
      indicate that the inhibition of HER2-induced tumorigenesis by miR-489
      overexpression was due to altering progenitor cell populations while decreasing
      tumor growth and metastasis via influencing tumor promoting genes DEK and SHP2.

PMID- 30104711
TI  - The role of PIP5K1alpha/pAKT and targeted inhibition of growth of subtypes of
      breast cancer using PIP5K1alpha inhibitor.
AB  - Despite recent improvement in adjuvant therapies, triple-negative, and ER+
      subtypes of breast cancer (BC) with metastatic potentials remain the leading
      cause of BC-related deaths. We investigated the role of phosphatidylinositol-4
      phosphate 5-kinase alpha (PIP5Kalpha), a key upstream factor of PI3K/AKT, and the
      therapeutic effect of PIP5Kalpha inhibitor on subtypes of BC. The clinical
      importance of PIP5K1alpha and its association with survivals were analyzed using
      three BC cohorts from Nottingham (n = 913), KM plotter (n = 112) and TCGA (n =
      817). Targeted overexpression or knockdown of PIP5K1alpha were introduced into BC
      cell lines. The effects of PIP5K1alpha and its inhibitor on growth and invasion
      of BC were confirmed by using in vitro assays including proliferation, migration,
      apoptosis and luciferase reporter assays and in vivo xenograft mouse models. All
      statistical tests were two-sided. PIP5K1alpha was associated with poor patient
      outcome in triple-negative BC (for PIP5K1alpha protein, p = 0.011 and for mRNA
      expression, p = 0.028, log-rank test). 29% of triple-negative BC had PIP5K1A gene
      amplification. Elevated level of PIP5K1alpha increased expression of pSer-473 AKT
      (p < 0.001) and invasiveness of triple-negative MDA-MB-231 cells (p < 0.001).
      Conversely, inhibition of PIP5K1alpha using its inhibitor ISA-2011B, or via
      knockdown suppressed growth and invasiveness of MDA-MB-231 xenografts (mean
      vehicle-treated controls = 2160 mm3, and mean ISA-2011B-treated = 600 mm3, p <
      0.001). ISA-2011B-treatment reduced expression of pSer-473 AKT (p < 0.001) and
      its downstream effectors including cyclin D1, VEGF and its receptors, VEGFR1 and
      VEGFR2 (p < 0.001) in xenograft tumors. In ER+ cancer cells, PIP5K1alpha acted on
      pSer-473 AKT, and was in complexes with VEGFR2, serving as co-factor of ER-alpha
      to regulate activities of target genes including cyclin D1 and CDK1. Our study
      suggests that our developed PIP5K1alpha inhibitor has a great potential on
      refining targeted therapeutics for treatment of triple-negative and ER+ BC with
      abnormal PI3K/AKT pathways.

PMID- 30104712
TI  - Polo-like kinases and acute leukemia.
AB  - Acute leukemia is a common malignancy among children and adults worldwide and
      many patients suffer from chronic health issues using current therapeutic
      approaches. Therefore, there is a great need for the development of novel and
      more specific therapies with fewer side effects. The family of Polo-like kinases
      (Plks) is a group of five serine/threonine kinases that play an important role in
      cell cycle regulation and are critical targets for therapeutic invention. Plk1
      and Plk4 are novel targets for cancer therapy as leukemic cells often express
      higher levels than normal cells. In contrast, Plk2 and Plk3 are considered to be
      tumor suppressors. Several small molecule inhibitors have been developed for
      targeting Plk1 inhibition. Despite reaching phase III clinical trials, one of the
      ATP-competitive Plk1 inhibitor, volasertib, did not induce an objective clinical
      response and even caused lethal side effects in some patients. In order to
      improve the specificity of the Plk1 inhibitors and reduce off-target side
      effects, novel RNA interference (RNAi)-based therapies have been developed. In
      this review, we summarize the mechanisms of action of the Plk family members in
      acute leukemia, describe preclinical studies and clinical trials involving Plk
      targeting drugs and discuss novel approaches in Plk targeting.

PMID- 30104709
TI  - Learning auditory discriminations from observation is efficient but less robust
      than learning from experience.
AB  - Social learning enables complex societies. However, it is largely unknown how
      insights obtained from observation compare with insights gained from trial-and
      error, in particular in terms of their robustness. Here, we use aversive
      reinforcement to train "experimenter" zebra finches to discriminate between
      auditory stimuli in the presence of an "observer" finch. We show that
      experimenters are slow to successfully discriminate the stimuli, but immediately
      generalize their ability to a new set of similar stimuli. By contrast, observers
      subjected to the same task are able to discriminate the initial stimulus set, but
      require more time for successful generalization. Drawing on concepts from machine
      learning, we suggest that observer learning has evolved to rapidly absorb sensory
      statistics without pressure to minimize neural resources, whereas learning from
      experience is endowed with a form of regularization that enables robust
      inference.

PMID- 30104714
TI  - Double (mtRNA) trouble.

PMID- 30104715
TI  - In situ transcriptome characteristics are lost following culture adaptation of
      adult cardiac stem cells.
AB  - Regenerative therapeutic approaches for myocardial diseases often involve
      delivery of stem cells expanded ex vivo. Prior studies indicate that cell culture
      conditions affect functional and phenotypic characteristics, but relationship(s)
      of cultured cells derived from freshly isolated populations and the heterogeneity
      of the cultured population remain poorly defined. Functional and phenotypic
      characteristics of ex vivo expanded cells will determine outcomes of
      interventional treatment for disease, necessitating characterization of the
      impact that ex vivo expansion has upon isolated stem cell populations. Single
      cell RNA-Seq profiling (scRNA-Seq) was performed to determine consequences of
      culture expansion upon adult cardiac progenitor cells (CPCs) as well as
      relationships with other cell populations. Bioinformatic analyses demonstrate
      that identity marker genes expressed in freshly isolated cells become
      undetectable in cultured CPCs while low level expression emerges for thousands of
      other genes. Transcriptional profile of CPCs exhibited greater degree of
      similarity throughout the cultured population relative to freshly isolated cells.
      Findings were validated by comparative analyses using scRNA-Seq datasets of
      various cell types generated by multiple scRNA-Seq technology. Increased
      transcriptome diversity and decreased population heterogeneity in the cultured
      cell population may help account for reported outcomes associated with
      experimental and clinical use of CPCs for treatment of myocardial injury.

PMID- 30104717
TI  - Post-remission strategies for the prevention of relapse following allogeneic
      hematopoietic cell transplantation for high-risk acute myeloid leukemia: expert
      review from the Acute Leukemia Working Party of the European Society for Blood
      and Marrow Transplantation.
AB  - Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy generally
      associated with poor prognosis. Allogeneic hematopoietic cell transplantation
      (alloHCT) continues to be the most potent anti-leukemia treatment for adult
      patients with intermediate and high-risk AML. However, disease relapse after
      alloHCT remains unacceptably high and is the primary cause of treatment failure
      and mortality following alloHCT. It is therefore that post-transplant early
      cellular or pharmacologic maintenance or preemptive strategies to enhance the
      graft-versus-leukemia effect or to eradicate persistent minimal residual disease
      have been of renewed interest, particularly with the availability of more
      sensitive technologies to measure residual AML. Although preliminary studies have
      demonstrated improved outcomes with the use of post-alloHCT remission therapies,
      prospective randomized trials are required to determine their clinical efficacy
      and role in the treatment of AML. On behalf of the Acute Leukemia Working Party
      of the European Society for Blood and Marrow Transplantation, we summarize the
      available evidence on the use and efficacy of available pharmacologic post
      remission therapies, including hypomethylating agents, deacetylase inhibitors,
      and tyrosine kinase inhibitors, as well as cellular therapies, including
      preemptive and prophylactic donor lymphocyte infusions for the prevention of
      relapse of AML.

PMID- 30104713
TI  - Delay-Induced Multistability and Loop Formation in Neuronal Networks with Spike
      Timing-Dependent Plasticity.
AB  - Spike-timing-dependent plasticity (STDP) adjusts synaptic strengths according to
      the precise timing of pre- and postsynaptic spike pairs. Theoretical and
      computational studies have revealed that STDP may contribute to the emergence of
      a variety of structural and dynamical states in plastic neuronal populations. In
      this manuscript, we show that by incorporating dendritic and axonal propagation
      delays in recurrent networks of oscillatory neurons, the asymptotic connectivity
      displays multistability, where different structures emerge depending on the
      initial distribution of the synaptic strengths. In particular, we show that the
      standard deviation of the initial distribution of synaptic weights, besides its
      mean, determines the main properties of the emergent structural connectivity such
      as the mean final synaptic weight, the number of two-neuron loops and the
      symmetry of the final structure. We also show that the firing rates of the
      neurons affect the evolution of the network, and a more symmetric configuration
      of the synapses emerges at higher firing rates. We justify the network results
      based on a two-neuron framework and show how the results translate to large
      recurrent networks.

PMID- 30104716
TI  - Iridophores as a source of robustness in zebrafish stripes and variability in
      Danio patterns.
AB  - Zebrafish (Danio rerio) feature black and yellow stripes, while related Danios
      display different patterns. All these patterns form due to the interactions of
      pigment cells, which self-organize on the fish skin. Until recently, research
      focused on two cell types (melanophores and xanthophores), but newer work has
      uncovered the leading role of a third type, iridophores: by carefully
      orchestrated transitions in form, iridophores instruct the other cells, but
      little is known about what drives their form changes. Here we address this
      question from a mathematical perspective: we develop a model (based on known
      interactions between the original two cell types) that allows us to assess
      potential iridophore behavior. We identify a set of mechanisms governing
      iridophore form that is consistent across a range of empirical data. Our model
      also suggests that the complex cues iridophores receive may act as a key source
      of redundancy, enabling both robust patterning and variability within Danio.

PMID- 30104718
TI  - High-dose chemotherapy and autologous stem cell transplantation in enteropathy
      associated and other aggressive T-cell lymphomas: a UK NCRI/Cancer Research UK
      Phase II Study.

PMID- 30104719
TI  - Premature coronary artery disease following allogeneic stem cell transplantation:
      an NHLBI Cohort Study.

PMID- 30104720
TI  - Incidence and risk factors of secondary cancers after allogeneic stem cell
      transplantation: analysis of a single centre cohort with a long follow-up.

PMID- 30104721
TI  - Highly reduced and protonated aqueous solutions of [P2W18O62]6- for on-demand
      hydrogen generation and energy storage.
AB  - As our reliance on renewable energy sources grows, so too does our need to store
      this energy to mitigate against troughs in supply. Energy storage in batteries or
      by conversion to chemical fuels are the two most flexible and scalable options,
      but are normally considered mutually exclusive. Energy storage solutions that can
      act as both batteries and fuel generation devices (depending on the requirements
      of the user) could therefore revolutionize the uptake and use of renewably
      generated energy. Here, we present a polyoxoanion, [P2W18O62]6-, that can be
      reversibly reduced and protonated by 18 electrons/H+ per anion in aqueous
      solution, and that can act either as a high-performance redox flow battery
      electrolyte (giving a practical discharged energy density of 225 Wh l-1 with a
      theoretical energy density of more than 1,000 Wh l-1), or as a mediator in an
      electrolytic cell for the on-demand generation of hydrogen.

PMID- 30104722
TI  - Hydrolytic stability in hemilabile metal-organic frameworks.
AB  - Highly porous metal-organic frameworks (MOFs), which have undergone exciting
      developments over the past few decades, show promise for a wide range of
      applications. However, many studies indicate that they suffer from significant
      stability issues, especially with respect to their interactions with water, which
      severely limits their practical potential. Here we demonstrate how the presence
      of 'sacrificial' bonds in the coordination environment of its metal centres
      (referred to as hemilability) endows a dehydrated copper-based MOF with good
      hydrolytic stability. On exposure to water, in contrast to the indiscriminate
      breaking of coordination bonds that typically results in structure degradation,
      it is non-structural weak interactions between the MOF's copper paddlewheel
      clusters that are broken and the framework recovers its as-synthesized, hydrated
      structure. This MOF retained its structural integrity even after contact with
      water for one year, whereas HKUST-1, a compositionally similar material that
      lacks these sacrificial bonds, loses its crystallinity in less than a day under
      the same conditions.

PMID- 30104723
TI  - Light-driven molecular trap enables bidirectional manipulation of dynamic
      covalent systems.
AB  - Bond formation between two molecular entities in a closed system strictly obeys
      the principle of microscopic reversibility and occurs in favour of the
      thermodynamically more stable product. Here, we demonstrate how light can bypass
      this fundamental limitation by driving and controlling the reversible bimolecular
      reaction between an N-nucleophile and a photoswitchable carbonyl electrophile.
      Light-driven tautomerization cycles reverse the reactivity of the C=O/C=N
      electrophiles ('umpolung') to activate substrates and remove products,
      respectively, solely depending on the illumination wavelength. By applying either
      red or blue light, selective and nearly quantitative intermolecular bond
      formation/scission can be achieved, even if the underlying
      condensation/hydrolysis equilibrium is thermodynamically disfavoured. Exploiting
      light-driven in situ C=N exchange, our approach can be used to externally
      regulate a closed dynamic covalent system by actively and reversibly removing
      specific components, resembling a molecular and bidirectional version of a
      macroscopic Dean-Stark trap.

PMID- 30104725
TI  - PPARgamma agonists: potential treatment for autism spectrum disorder by
      inhibiting the canonical WNT/beta-catenin pathway.
AB  - Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is
      characterized by a deficit in social interactions and communication with
      repetitive and restrictive behavior. No curative treatments are available for
      ASD. Pharmacological treatments do not address the core ASD behaviors, but target
      comorbid symptoms. Dysregulation of the core neurodevelopmental pathways is
      associated with the clinical presentation of ASD, and the canonical WNT/beta
      catenin pathway is one of the major pathways involved. The canonical WNT/beta
      catenin pathway participates in the development of the central nervous system,
      and its dysregulation involves developmental cognitive disorders. In numerous
      tissues, the canonical WNT/beta-catenin pathway and peroxisome proliferator
      activated receptor gamma (PPARgamma) act in an opposed manner. In ASD, the
      canonical WNT/beta-catenin pathway is increased while PPARgamma seems to be
      decreased. PPARgamma agonists present a beneficial effect in treatment for ASD
      children through their anti-inflammatory role. Moreover, they induce the
      inhibition of the canonical WNT/beta-catenin pathway in several
      pathophysiological states. We focus this review on the hypothesis of an opposed
      interplay between PPARgamma and the canonical WNT/beta-catenin pathway in ASD and
      the potential role of PPARgamma agonists as treatment for ASD.

PMID- 30104726
TI  - The Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS):
      progress toward understanding suicide among soldiers.
AB  - Responding to an unprecedented increase in the suicide rate among soldiers, in
      2008 the US Army and US National Institute of Mental Health funded the Army Study
      to Assess Risk and Resilience in Servicemembers (Army STARRS), a multicomponent
      epidemiological and neurobiological study of risk and resilience factors for
      suicidal thoughts and behaviors, and their psychopathological correlates among
      Army personnel. Using a combination of administrative records, representative
      surveys, computerized neurocognitive tests, and blood samples, Army STARRS and
      its longitudinal follow-up study (STARRS-LS) are designed to identify potentially
      actionable findings to inform the Army's suicide prevention efforts. The current
      report presents a broad overview of Army STARRS and its findings to date on
      suicide deaths, attempts, and ideation, as well as other important outcomes that
      may increase suicide risk (e.g., mental disorders, sexual assault victimization).
      The findings highlight the complexity of environmental and genetic risk and
      protective factors in different settings and contexts, and the importance of life
      and career history in understanding suicidal thoughts and behaviors.

PMID- 30104724
TI  - RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-,
      NF1- and RAS-driven cancers.
AB  - Oncogenic alterations in the RAS/RAF/MEK/ERK pathway drive the growth of a wide
      spectrum of cancers. While BRAF and MEK inhibitors are efficacious against
      BRAFV600E-driven cancers, effective targeted therapies are lacking for most
      cancers driven by other pathway alterations, including non-V600E oncogenic BRAF,
      RAS GTPase-activating protein (GAP) NF1 (neurofibromin 1) loss and oncogenic
      KRAS. Here, we show that targeting the SHP2 phosphatase (encoded by PTPN11) with
      RMC-4550, a small-molecule allosteric inhibitor, is effective in human cancer
      models bearing RAS-GTP-dependent oncogenic BRAF (for example, class 3 BRAF
      mutants), NF1 loss or nucleotide-cycling oncogenic RAS (for example, KRASG12C).
      SHP2 inhibitor treatment decreases oncogenic RAS/RAF/MEK/ERK signalling and
      cancer growth by disrupting SOS1-mediated RAS-GTP loading. Our findings
      illuminate a critical function for SHP2 in promoting oncogenic RAS/MAPK pathway
      activation in cancers with RAS-GTP-dependent oncogenic BRAF, NF1 loss and
      nucleotide-cycling oncogenic KRAS. SHP2 inhibition is a promising molecular
      therapeutic strategy for patients with cancers bearing these oncogenic drivers.

PMID- 30104727
TI  - Network changes associated with transdiagnostic depressive symptom improvement
      following cognitive behavioral therapy in MDD and PTSD.
AB  - Despite widespread use of cognitive behavioral therapy (CBT) in clinical
      practice, its mechanisms with respect to brain networks remain sparsely
      described. In this study, we applied tools from graph theory and network science
      to better understand the transdiagnostic neural mechanisms of this treatment for
      depression. A sample of 64 subjects was included in a study of network dynamics:
      33 patients (15 MDD, 18 PTSD) received longitudinal fMRI resting state scans
      before and after 12 weeks of CBT. Depression severity was rated on the Montgomery
      Asberg Depression Rating Scale (MADRS). Thirty-one healthy controls were included
      to determine baseline network roles. Univariate and multivariate regression
      analyses were conducted on the normalized change scores of within- and between
      system connectivity and normalized change score of the MADRS. Penalized
      regression was used to select a sparse set of predictors in a data-driven manner.
      Univariate analyses showed greater symptom reduction was associated with an
      increased functional role of the Ventral Attention (VA) system as an incohesive
      provincial system (decreased between- and decreased within-system connectivity).
      Multivariate analyses selected between-system connectivity of the VA system as
      the most prominent feature associated with depression improvement. Observed VA
      system changes are interesting in light of brain controllability descriptions:
      attentional control systems, including the VA system, fall on the boundary
      between-network communities, and facilitate integration or segregation of diverse
      cognitive systems. Thus, increasing segregation of the VA system following CBT
      (decreased between-network connectivity) may result in less contribution of
      emotional attention to cognitive processes, thereby potentially improving
      cognitive control.

PMID- 30104729
TI  - Translating advice to eat more vegetables into practice: observations from a 12
      month weight loss trial.
AB  - OBJECTIVES: This study aimed to identify the main vegetable sources of overweight
      participants during a 12-month randomised controlled trial for weight loss.
      METHODS: Secondary analysis using data from diet history interviews to determine
      changes to daily vegetable intake amounts and types throughout the trial at 0, 3
      and 12 months. RESULTS: Pre-trial 77% participants consumed frozen vegetables. At
      baseline (n = 113, 85 F), participants reported 345 +/- 170 (56-920) g/day
      vegetables increasing to 498 +/- 180 (146-930) g/day at 3 months and remaining
      stable at 475 +/- 169(170-1053) g/day by 12 months (p = 0.001). At baseline, 32
      of 34 different vegetable categories were reported, mainly tomato (69.9 g/day)
      and, potato (58.2 g/day). After 3 months (n = 109), seven vegetables remained in
      the top 10 reported (contributing 72%). Tomato remained top ranked to 12 months.
      CONCLUSION: Following advice to consume more vegetables, consumption increased
      above the Australian Dietary recommendation of ~375 g/day. Tomatoes remained a
      mainstay regardless of the time of year, but choices changed with time. Frozen
      vegetables may be a feasible option.

PMID- 30104730
TI  - Dietary diversity and healthy life expectancy-an international comparative study.
AB  - BACKGROUND/OBJECTIVES: The prolongation of healthy life expectancy (HALE) is a
      core issue of health policy in many countries. The purpose of this study is to
      clarify the relationship between dietary diversity and HALE using international
      databases. MATERIALS/METHODS: HALE data by country were derived from the Global
      Burden of Disease (GBD) 2015 database. Average food supply (g/day/capita) and
      energy supply (kcal/day/capita) by country, excluding loss between production and
      household, were obtained from the Food and Agriculture Organization of the United
      Nations Statistics Division database. Each food was sorted across 12 food groups,
      and dietary diversity was obtained from food groups using the Quantitative Index
      for Dietary Diversity (QUANTIDD). The cross-sectional and longitudinal
      associations between QUANTIDD and HALE were examined in the countries with
      populations of one million or greater. RESULTS: Cross-sectional analysis showed
      that HALE was significantly associated with QUANTIDD (beta = 99.9 +/- 11.4, p <
      0.001) in the single regression model and in the multiple regression model
      controlled for covariates (beta = 36.4 +/- 11.3, p = 0.002). Longitudinal
      analysis showed that HALE increased with QUANTIDD during the 15-year study period
      (beta = 46.4 +/- 5.1, p < 0.001), and this association was also significant when
      controlled for covariates (beta = 39.7 +/- 5.1, p < 0.001). Longitudinal
      association of QUANTIDD with the percentage difference between life expectancy
      and HALE controlled for covariates was significantly negative (beta = - 1.3 +/-
      0.5, p = 0.011). CONCLUSIONS: After controlling for socioeconomic indicators,
      longer healthy life is enjoyed by populations of countries with greater dietary
      diversity.

PMID- 30104728
TI  - Sex-specific impact of prenatal androgens on social brain default mode
      subsystems.
AB  - Early-onset neurodevelopmental conditions (e.g., autism) affect males more
      frequently than females. Androgens may play a role in this male-bias by sex
      differentially impacting early prenatal brain development, particularly neural
      circuits that later develop specialized roles in social cognition. Here, we find
      that increasing prenatal testosterone in humans is associated with later
      reduction of functional connectivity between social brain default mode (DMN)
      subsystems in adolescent males, but has no effect in females. Since testosterone
      can work directly via the androgen receptor (AR) or indirectly via the estrogen
      receptor through aromatase conversion to estradiol, we further examined how a
      potent non-aromatizable androgen, dihydrotestosterone (DHT), acts via the AR to
      influence gene expression in human neural stem cells (hNSC)-particularly for
      genes of high-relevance for DMN circuitry. DHT dysregulates a number of genes
      enriched for syndromic causes of autism and intellectual disability and for genes
      that in later development are expressed in anatomical patterns that highly
      correspond to the cortical midline DMN subsystem. DMN-related and DHT-affected
      genes (e.g., MEF2C) are involved in a number of synaptic processes, many of which
      impact excitation-inhibition balance. Androgens have male-specific prenatal
      influence over social brain circuitry in humans and may be relevant towards
      explaining some component of male-bias in early-onset neurodevelopmental
      conditions.

PMID- 30104732
TI  - Mapping projections of molecularly defined dopamine neuron subtypes using
      intersectional genetic approaches.
AB  - Midbrain dopamine (DA) neurons have diverse functions that can in part be
      explained by their heterogeneity. Although molecularly distinct subtypes of DA
      neurons have been identified by single-cell gene expression profiling,
      fundamental features such as their projection patterns have not been elucidated.
      Progress in this regard has been hindered by the lack of genetic tools for
      studying DA neuron subtypes. Here we develop intersectional genetic labeling
      strategies, based on combinatorial gene expression, to map the projections of
      molecularly defined DA neuron subtypes. We reveal distinct genetically defined
      dopaminergic pathways arising from the substantia nigra pars compacta and from
      the ventral tegmental area that innervate specific regions of the caudate
      putamen, nucleus accumbens and amygdala. Together, the genetic toolbox and DA
      neuron subtype projections presented here constitute a resource that will
      accelerate the investigation of this clinically significant neurotransmitter
      system.

PMID- 30104731
TI  - Sexually dimorphic behavior, neuronal activity, and gene expression in Chd8
      mutant mice.
AB  - Autism spectrum disorders (ASDs) are four times more common in males than in
      females, but the underlying mechanisms are poorly understood. We characterized
      sexually dimorphic changes in mice carrying a heterozygous mutation in Chd8
      (Chd8+/N2373K) that was first identified in human CHD8 (Asn2373LysfsX2), a strong
      ASD-risk gene that encodes a chromatin remodeler. Notably, although male mutant
      mice displayed a range of abnormal behaviors during pup, juvenile, and adult
      stages, including enhanced mother-seeking ultrasonic vocalization, enhanced
      attachment to reunited mothers, and isolation-induced self-grooming, their female
      counterparts do not. This behavioral divergence was associated with sexually
      dimorphic changes in neuronal activity, synaptic transmission, and transcriptomic
      profiles. Specifically, female mice displayed suppressed baseline neuronal
      excitation, enhanced inhibitory synaptic transmission and neuronal firing, and
      increased expression of genes associated with extracellular vesicles and the
      extracellular matrix. Our results suggest that a human CHD8 mutation leads to
      sexually dimorphic changes ranging from transcription to behavior in mice.

PMID- 30104733
TI  - Serotonin receptor 2c-expressing cells in the ventral CA1 control attention via
      innervation of the Edinger-Westphal nucleus.
AB  - The hippocampus is divided into dorsal and ventral zones along its principal
      axis. The dorsal hippocampus is critical for learning and memory, yet the basic
      function of the ventral hippocampus remains elusive. Here we genetically
      manipulate a subset of excitatory neurons expressing the serotonin receptor 2c
      (Htr2c) in the ventral hippocampus. Genetically modified virus tracing reveals
      that these Htr2c cells establish monosynaptic excitatory connections with newly
      identified neurons in the Edinger-Westphal nucleus (EW), which directly innervate
      the medial prefrontal cortex. Inactivation of Htr2c cells impairs behavioral
      performance in a visual-detection task that demands attention, without affecting
      novel-object recognition, learning, or memory. This attention deficit was
      recapitulated by inhibition of EW cells and rescued by activation of EW cells or
      synaptic projections from Htr2c cells onto EW cells. This study uncovers a
      synaptic pathway for control of attention.

PMID- 30104735
TI  - Investigation of the mechanism of chromium removal in (3
      aminopropyl)trimethoxysilane functionalized mesoporous silica.
AB  - We are proposed that a possible mechanism for Cr(VI) removal by functionalized
      mesoporous silica. Mesoporous silica was functionalized with (3
      aminopropyl)trimethoxysilane (APTMS) using the post-synthesis grafting method.
      The synthesized materials were characterized using transmission electron
      microscopy (TEM), X-ray diffraction (XRD), N2 adsorption-desorption analysis,
      Fourier-transform infrared (FT-IR), thermogravimetric analyses (TGA), and X-ray
      photoelectron spectroscopy (XPS) to confirm the pore structure and
      functionalization of amine groups, and were subsequently used as adsorbents for
      the removal of Cr(VI) from aqueous solution. As the concentration of APTMS
      increases from 0.01 M to 0.25 M, the surface area of mesoporous silica decreases
      from 857.9 m2/g to 402.6 m2/g. In contrast, Cr(VI) uptake increases from 36.95
      mg/g to 83.50 mg/g. This indicates that the enhanced Cr(VI) removal was primarily
      due to the activity of functional groups. It is thought that the optimum
      concentration of APTMS for functionalization is approximately 0.05 M. According
      to XPS data, NH3+ and protonated NH2 from APTMS adsorbed anionic Cr(VI) by
      electrostatic interaction and changed the solution pH. Equilibrium data are well
      fitted by Temkin and Sips isotherms. This research shows promising results for
      the application of amino functionalized mesoporous silica as an adsorbent to
      removal Cr(VI) from aqueous solution.

PMID- 30104734
TI  - Voluntary urination control by brainstem neurons that relax the urethral
      sphincter.
AB  - Voluntary urination ensures that waste is eliminated when safe and socially
      appropriate, even without a pressing urge. Uncontrolled urination, or
      incontinence, is a common problem with few treatment options. Normal urine
      release requires a small region in the brainstem known as Barrington's nucleus
      (Bar), but specific neurons that relax the urethral sphincter and enable urine
      flow are unknown. Here we identify a small subset of Bar neurons that control the
      urethral sphincter in mice. These excitatory neurons express estrogen receptor 1
      (BarESR1), project to sphincter-relaxing interneurons in the spinal cord and are
      active during natural urination. Optogenetic stimulation of BarESR1 neurons
      rapidly initiates sphincter bursting and efficient voiding in anesthetized and
      behaving animals. Conversely, optogenetic and chemogenetic inhibition reveals
      their necessity in motivated urination behavior. The identification of these
      cells provides an expanded model for the control of urination and its
      dysfunction.

PMID- 30104736
TI  - Evidence for Ussurian tube-nosed bats (Murina ussuriensis) hibernating in snow.
AB  - Surviving winter is a challenge for endothermic animals living at high latitudes.
      In bats, some species migrate to milder climates in winter, but others presumably
      stay and hibernate in thermally buffered roosts. However, we know little about
      where, or in what roosts bats hibernate. Ussurian tube-nosed bats (Murina
      ussuriensis) have occasionally been observed under or near the surface of snow.
      We collected the details of those accounts and used our own observations to
      conclude that these bats hibernate in snow. To our knowledge, this is the first
      evidence of hibernation in snow for bats, and second for mammals, following polar
      bears (Ursus maritimus) denning in snow.

PMID- 30104737
TI  - Groundwater depletion causing reduction of baseflow triggering Ganges river
      summer drying.
AB  - In summer (pre-monsoon) of recent years, low water level among the last few
      decades, has been observed in several lower Indian reaches of the Ganges (or
      Ganga) river (with estimated river water level depletion rates at the range of 
      0.5 to -38.1 cm/year between summers of 1999 and 2013 in the studied reaches).
      Here, we show this Ganges river depletion is related to groundwater baseflow
      reduction caused by ongoing observed groundwater storage depletion in the
      adjoining Gangetic aquifers (Ganges basin, -0.30 +/- 0.07 cm/year or -2.39 +/-
      0.56 km3/year). Our estimates show, 2016-baseflow amount (~1.0 * 106 m3/d) has
      reduced by ~59%, from the beginning of the irrigation-pumping age of 1970s (2.4 *
      106 m3/d) in some of the lower reaches. The net Ganges river water reduction
      could jeopardize domestic water supply, irrigation water requirements, river
      transport, ecology etc. of densely populated northern Indian plains. River water
      reduction has direct impact on food production indicating vulnerability to more
      than 100 million of the population residing in the region. The results of this
      study could be used to decipher the groundwater-linked river water depletion as
      well as the regional water security in other densely populated parts of the
      globe.

PMID- 30104738
TI  - Endogenous HIF2A reporter systems for high-throughput functional screening.
AB  - Tissue-specific transcriptional programs control most biological phenotypes,
      including disease states such as cancer. However, the molecular details
      underlying transcriptional specificity is largely unknown, hindering the
      development of therapeutic approaches. Here, we describe novel experimental
      reporter systems that allow interrogation of the endogenous expression of HIF2A,
      a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library
      targeting chromatin regulators, we provide evidence that these reporter systems
      are compatible with high-throughput screening. Our data also suggests redundancy
      in the control of cancer type-specific transcriptional traits. Reporter systems
      such as those described here could facilitate large-scale mechanistic dissection
      of transcriptional programmes underlying cancer phenotypes, thus paving the way
      for novel therapeutic approaches.

PMID- 30104739
TI  - A factor VII-based method for the prediction of anticoagulant response to
      warfarin.
AB  - Warfarin dosing methods based on existing models for warfarin and the
      international normalised ratio (INR) give biased maintenance dose predictions at
      the upper and lower quantiles of dose requirements. The aim of this work is to
      propose a conceptually different approach to predict INR after warfarin dosing.
      Factor VII concentration was proposed as the principal driving force for the INR.
      The time to steady-state INR (tSS,INR) was determined based on the INR response
      to changes in factor VII concentrations following warfarin initiation, and from
      this the steady-state INR (INRSS) was derived. The proposed method requires
      timed, paired blood samples of INR and factor VII. At different simulated
      warfarin dose rates, the prediction error associated with the proposed method was
      shown to be within clinically acceptable limits for both the tSS,INR (+/-2 days)
      and INRSS (+/-0.2). The use of the method was demonstrated in two patients who
      were initiated with 5 mg of warfarin daily. The difference in predicted versus
      actual steady-state INR were 0.0 and -0.4. The proposed method represents a
      unique approach to predict the INR. It considers factor VII as the main driver
      for INR and provides valuable information about the time to steady state INR.

PMID- 30104740
TI  - Turn-off colorimetric sensor for sequence-specific recognition of single-stranded
      DNA based upon Y-shaped DNA structure.
AB  - A novel turn-off colorimetric sensor for sequence-specific recognition of single
      stranded DNA (ssDNA) was established by combining Y-shaped DNA duplex and G
      quadruplex-hemin DNAzyme. A G-rich single-stranded DNA (Oligo-1) displays
      peroxidase mimicking catalytic activity due to the specific binding with hemin in
      the presence of K+, which was able to catalyze the oxidation of colorless 2,2'
      azinobis(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS2-) by H2O2 to generate
      green ABTS*- radical for colorimetric assay. Oligonucleotide 2 (Oligo-2) was
      partly complementary with Oligo-1 and the target DNA. Upon addition of target
      DNA, Oligo-1, Oligo-2 and target DNA can hybridize with each other to form Y
      shaped DNA duplex. The DNAzyme sequence of Oligo-1 was partly caged into Y-shaped
      DNA duplex, resulting in the inactivation of the DNAzyme and a sharp decrease of
      the absorbance of the oxidation product of ABTS2-. Under the optimum condition,
      the absorbance decreased linearly with the concentration of target DNA over the
      range of 1.0-250 nM and the detection limit was 0.95 nM (3sigma/slope) Moreover,
      satisfied result was obtained for the discrimination of single-base or two-base
      mismatched DNA.

PMID- 30104741
TI  - Biomimetic Super Anti-Wetting Coatings from Natural Materials: Superamphiphobic
      Coatings Based on Nanoclays.
AB  - Superamphiphobic coatings (SAPCs) that resist wetting of water and low-surface
      tension liquids have generated widespread attention in academia, but are very
      challenging to invent. Liquid adhesion, low stability, complicated and expensive
      preparation methods are the typical characteristics of SAPCs, which seriously
      hinder real-world applications of SAPCs. Here, we report a comprehensive study
      about preparation of SAPCs from abundant nanoclays with fibrous, plate-like and
      porous microstructures. The SAPCs are prepared simply by hydrolytic condensation
      of silanes in the presence of nanoclays, followed by spray-coating the as-formed
      suspensions onto substrates. The SAPCs feature high superamphiphobicity for
      various liquids down to a surface tension of 23.8 mN m-1 (n-decane), and high
      mechanical, chemical and thermal stability. The superamphiphobicity and stability
      depend on microscale and nanoscale surface morphology of the coatings, which are
      controllable by the microstructures of nanoclays and their acid activation. The
      fibrous nanoclays with moderate aspect ratio like palygorskite are the most
      suitable building blocks for the preparation of SAPCs by effectively forming the
      reentrant surface morphology. We believe that the findings will promote the
      progress of SAPCs, and pave the way for the development of clay-based super anti
      wetting coatings.

PMID- 30104742
TI  - Dislocation driven nanosample plasticity: new insights from quantitative in-situ
      TEM tensile testing.
AB  - Intrinsic dislocation mechanisms in the vicinity of free surfaces of an almost
      FIB damage-free single crystal Ni sample have been quantitatively investigated
      owing to a novel sample preparation method combining twin-jet electro-polishing,
      in-situ TEM heating and FIB. The results reveal that the small-scale plasticity
      is mainly controlled by the conversion of few tangled dislocations, still present
      after heating, into stable single arm sources (SASs) as well as by the successive
      operation of these sources. Strain hardening resulting from the operation of an
      individual SAS is reported and attributed to the decrease of the length of the
      source. Moreover, the impact of the shortening of the dislocation source on the
      intermittent plastic flow, characteristic of SASs, is discussed. These findings
      provide essential information for the understanding of the regime of 'dislocation
      source' controlled plasticity and the related mechanical size effect.

PMID- 30104744
TI  - The complex aetiology of cerebral palsy.
AB  - Cerebral palsy (CP) is the most prevalent, severe and costly motor disability of
      childhood. Consequently, CP is a public health priority for prevention, but its
      aetiology has proved complex. In this Review, we summarize the evidence for a
      decline in the birth prevalence of CP in some high-income nations, describe the
      epidemiological evidence for risk factors, such as preterm delivery and fetal
      growth restriction, genetics, pregnancy infection and other exposures, and
      discuss the success achieved so far in prevention through the use of magnesium
      sulfate in preterm labour and therapeutic hypothermia for birth-asphyxiated
      infants. We also consider the complexities of disentangling prenatal and
      perinatal influences, and of establishing subtypes of the disorder, with a view
      to accelerating the translation of evidence into the development of strategies
      for the prevention of CP.

PMID- 30104745
TI  - Multimodal imaging in RBD - present and future.

PMID- 30104743
TI  - PMLPR: A novel method for predicting subcellular localization based on
      recommender systems.
AB  - The importance of protein subcellular localization problem is due to the
      importance of protein's functions in different cell parts. Moreover, prediction
      of subcellular locations helps to identify the potential molecular targets for
      drugs and has an important role in genome annotation. Most of the existing
      prediction methods assign only one location for each protein. But, since some
      proteins move between different subcellular locations, they can have multiple
      locations. In recent years, some multiple location predictors have been
      introduced. However, their performances are not accurate enough and there is much
      room for improvement. In this paper, we introduced a method, PMLPR, to predict
      locations for a protein. PMLPR predicts a list of locations for each protein
      based on recommender systems and it can properly overcome the multiple location
      prediction problem. For evaluating the performance of PMLPR, we considered six
      datasets RAT, FLY, HUMAN, Du et al., DBMLoc and Hoglund. The performance of this
      algorithm is compared with six state-of-the-art algorithms, YLoc, WOLF-PSORT,
      prediction channel, MDLoc, Du et al. and MultiLoc2-HighRes. The results indicate
      that our proposed method is significantly superior on RAT and Fly proteins, and
      decent on HUMAN proteins. Moreover, on the datasets introduced by Du et al.,
      DBMLoc and Hoglund, PMLPR has comparable results. For the case study, we applied
      the algorithms on 8 proteins which are important in cancer research. The results
      of comparison with other methods indicate the efficiency of PMLPR.

PMID- 30104746
TI  - Traumatic brain injury induces transmissible tau pathology.

PMID- 30104748
TI  - Distinct cerebellar contributions to FTD subtypes.

PMID- 30104747
TI  - Familial PD gene involved in idiopathic disease.

PMID- 30104749
TI  - Tax havens and global environmental degradation.
AB  - The release of classified documents in the past years have offered a rare glimpse
      into the opaque world of tax havens and their role in the global economy.
      Although the political, economic and social implications related to these
      financial secrecy jurisdictions are known, their role in supporting economic
      activities with potentially detrimental environmental consequences have until now
      been largely ignored. Here, we combine quantitative analysis with case
      descriptions to elaborate and quantify the connections between tax havens and the
      environment, both in global fisheries and the Brazilian Amazon. We show that
      while only 4% of all registered fishing vessels are currently flagged in a tax
      haven, 70% of the known vessels implicated in illegal, unreported and unregulated
      fishing are, or have been, flagged under a tax haven jurisdiction. We also find
      that between October 2000 and August 2011, 68% of all investigated foreign
      capital to nine focal companies in the soy and beef sectors in the Brazilian
      Amazon was transferred through one, or several, known tax havens. This represents
      as much as 90-100% of foreign capital for some companies investigated. We
      highlight key research challenges for the academic community that emerge from our
      findings and present a set of proposed actions for policy that would put tax
      havens on the global sustainability agenda.

PMID- 30104750
TI  - Coupling of ecosystem-scale plant water storage and leaf phenology observed by
      satellite.
AB  - Plant water storage is fundamental to the functioning of terrestrial ecosystems
      by participating in plant metabolism, nutrient and sugar transport, and
      maintenance of the integrity of the hydraulic system of the plant. However, a
      global view of the size and dynamics of the water pools stored in plant tissues
      is still lacking. Here, we report global patterns of seasonal variations in
      ecosystem-scale plant water storage and their relationship with leaf phenology,
      based on space-borne measurements of L-band vegetation optical depth. We find
      that seasonal variations in plant water storage are highly synchronous with leaf
      phenology for the boreal and temperate forests, but asynchronous for the tropical
      woodlands, where the seasonal development of plant water storage lags behind leaf
      area by up to 180 days. Contrasting patterns of the time lag between plant water
      storage and terrestrial groundwater storage are also evident in these ecosystems.
      A comparison of the water cycle components in seasonally dry tropical woodlands
      highlights the buffering effect of plant water storage on the seasonal dynamics
      of water supply and demand. Our results offer insights into ecosystem-scale plant
      water relations globally and provide a basis for an improved parameterization of
      eco-hydrological and Earth system models.

PMID- 30104752
TI  - Breakdown of brain-body allometry and the encephalization of birds and mammals.
AB  - The allometric relationship between brain and body size among vertebrates is
      often considered a manifestation of evolutionary constraints. However, birds and
      mammals have undergone remarkable encephalization, in which brain size has
      increased without corresponding changes in body size. Here, we explore the
      hypothesis that a reduction of phenotypic integration between brain and body size
      has facilitated encephalization in birds and mammals. Using a large dataset
      comprising 20,213 specimens across 4,587 species of jawed vertebrates, we show
      that the among-species (evolutionary) brain-body allometries are remarkably
      constant, both across vertebrate classes and across taxonomic levels. Birds and
      mammals, however, are exceptional in that their within-species (static)
      allometries are shallower and more variable than in other vertebrates. These
      patterns are consistent with the idea that birds and mammals have reduced
      allometric constraints that are otherwise ubiquitous across jawed vertebrates.
      Further exploration of ontogenetic allometries in selected taxa of birds, fishes
      and mammals reveals that birds and mammals have extended the period of fetal
      brain growth compared to fishes. Based on these findings, we propose that avian
      and mammalian encephalization has been contingent on increased variability in
      brain growth patterns.

PMID- 30104751
TI  - Climate sensitive size-dependent survival in tropical trees.
AB  - Survival rates of large trees determine forest biomass dynamics. Survival rates
      of small trees have been linked to mechanisms that maintain biodiversity across
      tropical forests. How species survival rates change with size offers insight into
      the links between biodiversity and ecosystem function across tropical forests. We
      tested patterns of size-dependent tree survival across the tropics using data
      from 1,781 species and over 2 million individuals to assess whether tropical
      forests can be characterized by size-dependent life-history survival strategies.
      We found that species were classifiable into four 'survival modes' that explain
      life-history variation that shapes carbon cycling and the relative abundance
      within forests. Frequently collected functional traits, such as wood density,
      leaf mass per area and seed mass, were not generally predictive of the survival
      modes of species. Mean annual temperature and cumulative water deficit predicted
      the proportion of biomass of survival modes, indicating important links between
      evolutionary strategies, climate and carbon cycling. The application of survival
      modes in demographic simulations predicted biomass change across forest sites.
      Our results reveal globally identifiable size-dependent survival strategies that
      differ across diverse systems in a consistent way. The abundance of survival
      modes and interaction with climate ultimately determine forest structure, carbon
      storage in biomass and future forest trajectories.

PMID- 30104753
TI  - Caelestiventus hanseni gen. et sp. nov. extends the desert-dwelling pterosaur
      record back 65 million years.
AB  - Pterosaurs are the oldest known powered flying vertebrates. Originating in the
      Late Triassic, they thrived to the end of the Cretaceous. Triassic pterosaurs are
      extraordinarily rare and all but one specimen come from marine deposits in the
      Alps. A new comparatively large (wing span >150 cm) pterosaur, Caelestiventus
      hanseni gen. et sp. nov., from Upper Triassic desert deposits of western North
      America preserves delicate structural and pneumatic details not previously known
      in early pterosaurs, and allows a reinterpretation of crushed Triassic specimens.
      It shows that the earliest pterosaurs were geographically widely distributed and
      ecologically diverse, even living in harsh desert environments. It is the only
      record of desert-dwelling non-pterodactyloid pterosaurs and predates all known
      desert pterosaurs by more than 65 Myr. A phylogenetic analysis shows it is
      closely allied with Dimorphodon macronyx from the Early Jurassic of Britain.

PMID- 30104755
TI  - Robust regulations.

PMID- 30104756
TI  - Publisher Correction: Redefining ecosystem multifunctionality.
AB  - In the version of this Perspective originally published, in the figure in Box 3
      the middle panel of the top row was incorrectly labelled '50% threshold-plus'; it
      should have read '50% threshold'. This has now been corrected.

PMID- 30104754
TI  - Author Correction: Red fox genome assembly identifies genomic regions associated
      with tame and aggressive behaviours.
AB  - In the version of this Article originally published, there were some errors in
      the affiliations: Stephen J. O'Brien's affiliations were incorrectly listed as
      8,9; they should have been 7,9. Affiliation 3 was incorrectly named the Institute
      of Cytology and Genetics of the Russian Academy of Sciences; it should have read
      Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy
      of Sciences. Affiliation 4 was incorrectly named the Institute of Molecular and
      Cell Biology of the Russian Academy of Sciences; it should have read Institute of
      Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of
      Sciences. These have now been corrected.

PMID- 30104757
TI  - Automated Gleason grading of prostate cancer tissue microarrays via deep
      learning.
AB  - The Gleason grading system remains the most powerful prognostic predictor for
      patients with prostate cancer since the 1960s. Its application requires highly
      trained pathologists, is tedious and yet suffers from limited inter-pathologist
      reproducibility, especially for the intermediate Gleason score 7. Automated
      annotation procedures constitute a viable solution to remedy these limitations.
      In this study, we present a deep learning approach for automated Gleason grading
      of prostate cancer tissue microarrays with Hematoxylin and Eosin (H&E) staining.
      Our system was trained using detailed Gleason annotations on a discovery cohort
      of 641 patients and was then evaluated on an independent test cohort of 245
      patients annotated by two pathologists. On the test cohort, the inter-annotator
      agreements between the model and each pathologist, quantified via Cohen's
      quadratic kappa statistic, were 0.75 and 0.71 respectively, comparable with the
      inter-pathologist agreement (kappa = 0.71). Furthermore, the model's Gleason
      score assignments achieved pathology expert-level stratification of patients into
      prognostically distinct groups, on the basis of disease-specific survival data
      available for the test cohort. Overall, our study shows promising results
      regarding the applicability of deep learning-based solutions towards more
      objective and reproducible prostate cancer grading, especially for cases with
      heterogeneous Gleason patterns.

PMID- 30104758
TI  - Genome-wide identification of the auxin/indole-3-acetic acid (Aux/IAA) gene
      family in pepper, its characterisation, and comprehensive expression profiling
      under environmental and phytohormones stress.
AB  - Auxin is an essential phytohormone that plays a crucial role in the growth and
      development of plants in stressful environments. Here, we analysed the
      auxin/indole-3-acetic acid (Aux/IAA) gene family, which produces auxin in pepper,
      and succeeded in identifying 27 putative members containing four conserved
      domains (I. II. III and IV) in their protein sequences. Sequence analysis,
      chromosomal mapping and motif prediction of all identified CaAux/IAA genes were
      performed. It was observed that these genes contained four conserved motifs
      divided into nine different groups and distributed across nine chromosomes in
      pepper plants. RNA-seq analysis revealed the organ specific expression of many
      CaAux/IAA genes. However, the majority of genes were expressed with high
      expression levels in the early stages of fruit development. However, the maximum
      expression level of the CA03g34540 gene was observed in the breaker stage.
      Moreover, thirteen CaAux/IAA genes were labelled as early responsive genes to
      various phytohormone and abiotic stresses. Furthermore, RNA-seq analysis in
      response to pathogen inoculation (PepMoV, TMV strains P0/P1, and Phytophthora
      capsici) showed distinct expression profiles of all identified genes, suggesting
      the diverse expression nature of genes under these stress conditions. Overall,
      this study provides insight into the dynamic response of CaAux/IAA genes under
      environmental and phytohormones stress conditions, providing bases to further
      explore the importance of these genes through mutant/transgenic analysis in
      pepper.

PMID- 30104760
TI  - Estimation of complex effect-size distributions using summary-level statistics
      from genome-wide association studies across 32 complex traits.
AB  - We developed a likelihood-based approach for analyzing summary-level statistics
      and external linkage disequilibrium information to estimate effect-size
      distributions of common variants, characterized by the proportion of underlying
      susceptibility SNPs and a flexible normal-mixture model for their effects.
      Analysis of results available across 32 genome-wide association studies showed
      that, while all traits are highly polygenic, there is wide diversity in the
      degree and nature of polygenicity. Psychiatric diseases and traits related to
      mental health and ability appear to be most polygenic, involving a continuum of
      small effects. Most other traits, including major chronic diseases, involve
      clusters of SNPs that have distinct magnitudes of effects. We predict that the
      sample sizes needed to identify SNPs that explain most heritability found in
      genome-wide association studies will range from a few hundred thousand to
      multiple millions, depending on the underlying effect-size distributions of the
      traits. Accordingly, we project the risk-prediction ability of polygenic risk
      scores across a wide variety of diseases.

PMID- 30104759
TI  - High-throughput inference of pairwise coalescence times identifies signals of
      selection and enriched disease heritability.
AB  - Interest in reconstructing demographic histories has motivated the development of
      methods to estimate locus-specific pairwise coalescence times from whole-genome
      sequencing data. Here we introduce a powerful new method, ASMC, that can estimate
      coalescence times using only SNP array data, and is orders of magnitude faster
      than previous approaches. We applied ASMC to detect recent positive selection in
      113,851 phased British samples from the UK Biobank, and detected 12 genome-wide
      significant signals, including 6 novel loci. We also applied ASMC to sequencing
      data from 498 Dutch individuals to detect background selection at deeper time
      scales. We detected strong heritability enrichment in regions of high background
      selection in an analysis of 20 independent diseases and complex traits using
      stratified linkage disequilibrium score regression, conditioned on a broad set of
      functional annotations (including other background selection annotations). These
      results underscore the widespread effects of background selection on the genetic
      architecture of complex traits.

PMID- 30104761
TI  - Efficiently controlling for case-control imbalance and sample relatedness in
      large-scale genetic association studies.
AB  - In genome-wide association studies (GWAS) for thousands of phenotypes in large
      biobanks, most binary traits have substantially fewer cases than controls. Both
      of the widely used approaches, the linear mixed model and the recently proposed
      logistic mixed model, perform poorly; they produce large type I error rates when
      used to analyze unbalanced case-control phenotypes. Here we propose a scalable
      and accurate generalized mixed model association test that uses the saddlepoint
      approximation to calibrate the distribution of score test statistics. This
      method, SAIGE (Scalable and Accurate Implementation of GEneralized mixed model),
      provides accurate P values even when case-control ratios are extremely
      unbalanced. SAIGE uses state-of-art optimization strategies to reduce
      computational costs; hence, it is applicable to GWAS for thousands of phenotypes
      by large biobanks. Through the analysis of UK Biobank data of 408,961 samples
      from white British participants with European ancestry for > 1,400 binary
      phenotypes, we show that SAIGE can efficiently analyze large sample data,
      controlling for unbalanced case-control ratios and sample relatedness.

PMID- 30104762
TI  - Genome-wide polygenic scores for common diseases identify individuals with risk
      equivalent to monogenic mutations.
AB  - A key public health need is to identify individuals at high risk for a given
      disease to enable enhanced screening or preventive therapies. Because most common
      diseases have a genetic component, one important approach is to stratify
      individuals based on inherited DNA variation1. Proposed clinical applications
      have largely focused on finding carriers of rare monogenic mutations at several
      fold increased risk. Although most disease risk is polygenic in nature2-5, it has
      not yet been possible to use polygenic predictors to identify individuals at risk
      comparable to monogenic mutations. Here, we develop and validate genome-wide
      polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5,
      3.2, and 1.5% of the population at greater than threefold increased risk for
      coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel
      disease, and breast cancer, respectively. For coronary artery disease, this
      prevalence is 20-fold higher than the carrier frequency of rare monogenic
      mutations conferring comparable risk6. We propose that it is time to contemplate
      the inclusion of polygenic risk prediction in clinical care, and discuss relevant
      issues.

PMID- 30104764
TI  - Relatedness disequilibrium regression estimates heritability without
      environmental bias.
AB  - Heritability measures the proportion of trait variation that is due to genetic
      inheritance. Measurement of heritability is important in the nature-versus
      nurture debate. However, existing estimates of heritability may be biased by
      environmental effects. Here, we introduce relatedness disequilibrium regression
      (RDR), a novel method for estimating heritability. RDR avoids most sources of
      environmental bias by exploiting variation in relatedness due to random Mendelian
      segregation. We used a sample of 54,888 Icelanders who had both parents genotyped
      to estimate the heritability of 14 traits, including height (55.4%, s.e. 4.4%)
      and educational attainment (17.0%, s.e. 9.4%). Our results suggest that some
      other estimates of heritability may be inflated by environmental effects.

PMID- 30104763
TI  - Copy number signatures and mutational processes in ovarian carcinoma.
AB  - The genomic complexity of profound copy number aberrations has prevented
      effective molecular stratification of ovarian cancers. Here, to decode this
      complexity, we derived copy number signatures from shallow whole-genome
      sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were
      validated on 527 independent cases. We show that HGSOC comprises a continuum of
      genomes shaped by multiple mutational processes that result in known patterns of
      genomic aberration. Copy number signature exposures at diagnosis predict both
      overall survival and the probability of platinum-resistant relapse. Measurement
      of signature exposures provides a rational framework to choose combination
      treatments that target multiple mutational processes.

PMID- 30104765
TI  - Clinical Manifestations and Ophthalmic Outcomes of Ocular Syphilis at a Time of
      Re-Emergence of the Systemic Infection.
AB  - Recent reports from different world regions suggest ocular syphilis is re
      emerging, in parallel with an increasing incidence of the systemic infection
      globally. We conducted a large observational study of 127 persons consecutively
      treated for ocular syphilis at public medical centers in Brazil over a 2.5-year
      period ending July 2015. Of 104 individuals serologically tested for human
      immunodeficiency virus (HIV), 34.6% were positive. Ophthalmological evaluations
      included measurement of Snellen visual acuity and intraocular pressure, and
      assessment of inflammation by slit lamp examination and dilated posterior eye
      examination. Involvements in 214 eyes were anterior (6.1%), intermediate (8.4%),
      posterior (76.2%) and pan- (8.4%) uveitis, and scleritis (0.9%). Multiple
      anterior and posterior eye complications were observed, including cataract in the
      anterior eye (incidence rate, 0.18/eye-year) and epiretinal membrane in the
      posterior eye (incidence rate, 0.09/eye-year); incidence rates of reduction in
      best-corrected visual acuity to <=20/50 and <=20/200 were 0.10 and 0.06/eye-year,
      respectively. Rates of complications and visual acuity loss did not differ
      significantly between HIV- positive and negative individuals. In an era of re
      emergence, syphilis has ocular complications that may compromise vision, despite
      treatment with appropriate anti-microbial drugs.

PMID- 30104767
TI  - Automated deep-neural-network surveillance of cranial images for acute neurologic
      events.
AB  - Rapid diagnosis and treatment of acute neurological illnesses such as stroke,
      hemorrhage, and hydrocephalus are critical to achieving positive outcomes and
      preserving neurologic function-'time is brain'1-5. Although these disorders are
      often recognizable by their symptoms, the critical means of their diagnosis is
      rapid imaging6-10. Computer-aided surveillance of acute neurologic events in
      cranial imaging has the potential to triage radiology workflow, thus decreasing
      time to treatment and improving outcomes. Substantial clinical work has focused
      on computer-assisted diagnosis (CAD), whereas technical work in volumetric image
      analysis has focused primarily on segmentation. 3D convolutional neural networks
      (3D-CNNs) have primarily been used for supervised classification on 3D modeling
      and light detection and ranging (LiDAR) data11-15. Here, we demonstrate a 3D-CNN
      architecture that performs weakly supervised classification to screen head CT
      images for acute neurologic events. Features were automatically learned from a
      clinical radiology dataset comprising 37,236 head CTs and were annotated with a
      semisupervised natural-language processing (NLP) framework16. We demonstrate the
      effectiveness of our approach to triage radiology workflow and accelerate the
      time to diagnosis from minutes to seconds through a randomized, double-blinded,
      prospective trial in a simulated clinical environment.

PMID- 30104766
TI  - Sequestration of T cells in bone marrow in the setting of glioblastoma and other
      intracranial tumors.
AB  - T cell dysfunction contributes to tumor immune escape in patients with cancer and
      is particularly severe amidst glioblastoma (GBM). Among other defects, T cell
      lymphopenia is characteristic, yet often attributed to treatment. We reveal that
      even treatment-naive subjects and mice with GBM can harbor AIDS-level CD4 counts,
      as well as contracted, T cell-deficient lymphoid organs. Missing naive T cells
      are instead found sequestered in large numbers in the bone marrow. This
      phenomenon characterizes not only GBM but a variety of other cancers, although
      only when tumors are introduced into the intracranial compartment. T cell
      sequestration is accompanied by tumor-imposed loss of S1P1 from the T cell
      surface and is reversible upon precluding S1P1 internalization. In murine models
      of GBM, hindering S1P1 internalization and reversing sequestration licenses T
      cell-activating therapies that were previously ineffective. Sequestration of T
      cells in bone marrow is therefore a tumor-adaptive mode of T cell dysfunction,
      whose reversal may constitute a promising immunotherapeutic adjunct.

PMID- 30104768
TI  - Clinically applicable deep learning for diagnosis and referral in retinal
      disease.
AB  - The volume and complexity of diagnostic imaging is increasing at a pace faster
      than the availability of human expertise to interpret it. Artificial intelligence
      has shown great promise in classifying two-dimensional photographs of some common
      diseases and typically relies on databases of millions of annotated images. Until
      now, the challenge of reaching the performance of expert clinicians in a real
      world clinical pathway with three-dimensional diagnostic scans has remained
      unsolved. Here, we apply a novel deep learning architecture to a clinically
      heterogeneous set of three-dimensional optical coherence tomography scans from
      patients referred to a major eye hospital. We demonstrate performance in making a
      referral recommendation that reaches or exceeds that of experts on a range of
      sight-threatening retinal diseases after training on only 14,884 scans. Moreover,
      we demonstrate that the tissue segmentations produced by our architecture act as
      a device-independent representation; referral accuracy is maintained when using
      tissue segmentations from a different type of device. Our work removes previous
      barriers to wider clinical use without prohibitive training data requirements
      across multiple pathologies in a real-world setting.

PMID- 30104770
TI  - Author Correction: Metformin reverses established lung fibrosis in a bleomycin
      model.
AB  - In the version of this article originally published, a grant was omitted from the
      Acknowledgements section. The following sentence should have been included:
      "R.B.M. was supported by a Department of Veterans Affairs Merit Award
      (5I01BX003272)." The error has been corrected in the HTML and PDF versions of
      this article.

PMID- 30104769
TI  - Author Correction: Mutations in the SWI/SNF complex induce a targetable
      dependence on oxidative phosphorylation in lung cancer.
AB  - In the version of this article originally published, information regarding
      several funding sources was omitted from the Acknowledgements section. The
      following sentences should have been included: "This work was supported by the
      generous philanthropic contributions to The University of Texas MD Anderson Lung
      Cancer Moon Shots Program, the UT Lung SPORE 5 P50 CA07090, and the MD Anderson
      Cancer Center Support Grant P30CA01667. V.P is supported by R01CA155196-01A1 from
      the National Cancer Institute." Also, reference 18 was incorrect. The original
      reference was: Kim, E. S. et al. The BATTLE trial: personalizing therapy for lung
      cancer. Cancer Discov. 1, 44-53 (2011). It should have been: Papadimitrakopoulou,
      V. et al. The BATTLE-2 study: a biomarker-integrated targeted therapy study in
      previously treated patients with advanced non-small-cell lung cancer. J Clin.
      Oncol. 34, 3638-3647 (2016). The errors have been corrected in the HTML and PDF
      versions of this article.

PMID- 30104771
TI  - Cancer immunotherapy - a promising approach.

PMID- 30104772
TI  - Veterinary Medical Ethics.

PMID- 30104773
TI  - Massive uterine lipoleiomyoma and leiomyoma in a miniature poodle bitch.
AB  - A 15-year-old, intact, female miniature poodle was presented for further
      evaluation of a large abdominal mass. Computed tomography was conducted to
      determine the origin of the mass and 2 large uterine masses were discovered.
      Ovariohysterectomy was performed and histopathological evaluation revealed a
      massive uterine lipoleiomyoma (27 * 17 * 15 cm), the largest recorded in the
      veterinary literature, and a smaller leiomyoma (7 * 5 * 4 cm).

PMID- 30104774
TI  - Tonsillar plasmacytoma in a dog.
AB  - A 10-year-old greyhound dog was presented because of an incidental finding of a
      tonsillar mass. Excisional surgical biopsy was performed and the dog was
      diagnosed with an incompletely resected plasma cell tumor. Adjuvant therapy was
      declined. One year later there was no local recurrence or distant metastasis of
      the mass or clinical signs associated with the tonsillar plasmacytoma.

PMID- 30104775
TI  - Chondroblastic osteosarcoma of the middle ear in a guinea pig (Cavia porcellus).
AB  - A 3-year-old intact female guinea pig (Cavia porcellus) was presented for acute
      anorexia. Medical and surgical treatments for cystitis and ovarian cysts,
      respectively, did not prevent continuous weight loss. Computed tomography and
      histopathological analysis revealed a chondroblastic osteosarcoma of the right
      middle ear, which has not been reported in this species.

PMID- 30104776
TI  - Cerebral toxoplasmosis in a cat with feline leukemia and feline infectious
      peritonitis viral infections.
AB  - A diarrheic young cat died after neurological involvement. Biochemistry pointed
      to feline infectious peritonitis (FIP). The final diagnosis was severe multifocal
      meningoencephalitis due to Toxoplasma gondii. The presence of the parasite in the
      brain was confirmed using immunohistochemical staining. Concomitant feline
      leukemia virus (FeLV) and FIP were possible contributors to the clinical, fatal
      outcome.

PMID- 30104777
TI  - Hepatic Dicrocoelium dendriticum infection in a miniature horse.
AB  - A miniature horse which died following humane seizure from an Ontario farm was
      emaciated with serous atrophy of fat. Autopsy revealed hepatic atrophy and
      moderate periportal fibrosis. Eggs and trematodes seen in the liver were
      identified as Dicrocoelium dendriticum. This appears to be the first reported
      case of infection of equids in North America with Dicrocoelium dendriticum.

PMID- 30104778
TI  - Progressive ossifying paranasal sinus mass of suspected traumatic origin in a
      mare: Surgical treatment and follow-up.
AB  - This report describes a case of a multilobular, osseous mass including parts of
      the right orbit, concho frontal sinus and right ventral and dorsal conchal
      sinuses that developed after a traumatic insult to the right maxillary sinus 4
      years prior to presentation. Surgical removal of the mass including parts of the
      bony orbit and long-term outcome are reported.

PMID- 30104779
TI  - Musculoskeletal discomfort among Canadian bovine practitioners: Prevalence,
      impact on work, and perception of physically demanding tasks.
AB  - Musculoskeletal discomfort (MSD) is prevalent in large animal veterinarians but
      little research has been conducted on prevalence of MSD and its impact among
      Canadian bovine veterinarians. This 2017 survey targeted practicing and retired
      members of the Western Canadian Association of Bovine Practitioners, and adapted
      the Nordic Musculoskeletal Questionnaire to quantify MSD prevalence. Open-ended
      questions were used to determine the impact of MSD on work and to determine what
      were perceived to be the most physically demanding tasks. The survey response
      rate was 51.4% (133/259). Prevalence of MSD was high, with 12-month and lifetime
      rates of 89.5% and 96.9%, respectively. Obstetrical procedures, rectal
      examinations, and bull semen collections were reported as the 3 most physically
      strenuous tasks. The high MSD prevalence rates observed in the shoulder, neck,
      and lower back call for research on direct ergonomic assessments and work
      practice interventions for bovine veterinarians.

PMID- 30104780
TI  - Prevalence of and risk factors for equine glandular and squamous gastric disease
      in polo horses.
AB  - The objectives of this study were to determine the prevalence rates and risk
      factors for equine glandular gastric disease (EGGD) and equine squamous gastric
      disease (ESGD) in a population of 63 polo horses in competition. The prevalence
      of EGGD grade >= 1 was 69% and EGGD >= 2 was 31%. The prevalence of ESGD grade >=
      1 was 54% and grade >= 2 was 37%. The risk factors retained in the final
      multivariable models were years of experience in polo competition for EGGD grade
      >= 1 and for grade >= 2, with decreased experience being associated with EGGD and
      weekly exercise duration and non-steroidal anti-inflammatory drug (NSAID) use
      being associated with ESGD grade >= 1. Decreasing weekly exercise duration was
      the only risk factor associated with ESGD grade >= 2. Equine gastric disease was
      common in this population of polo horses and the amount of experience and weekly
      exercise duration were related to the risk of disease.

PMID- 30104781
TI  - Antimicrobial resistance in bacteria isolated from cats and dogs from the
      Atlantic Provinces, Canada from 1994-2013.
AB  - Antimicrobial susceptibility patterns and trends in bacteria isolated from cats
      and dogs were determined from diagnostic laboratory data from the Atlantic
      Veterinary College Diagnostic Services Bacteriology Laboratory over a 20-year
      period. Clinical samples were most commonly from the urinary tract and the ear.
      Staphylococcus spp. and Escherichia coli were the bacteria that were most
      frequently isolated. Increases in percentage resistant were seen with E. coli to
      cephalexin (57% to 61%), Pasteurella spp. to erythromycin (35% to 53%), and
      Pseudomonas aeruginosa (31% to 39%), and Streptococcus spp. (46% to 53%) to
      enrofloxacin. The frequency of resistance did not change significantly over the
      study period; however, increased enrofloxacin resistance was identified for
      canine isolates of Staphylococcus spp., Streptococcus spp., Enterococcus spp., E.
      coli, P. aeruginosa, and Proteus spp. Multidrug resistance was observed in 12%
      and 9% of the isolates from dogs and cats, respectively. Data from this study
      could be used to guide empirical antimicrobial selection in companion animal
      veterinary practices in Atlantic Canada.

PMID- 30104782
TI  - Laparoscopic-assisted ovariohysterectomy for the treatment of pyometra in a
      Bengal tiger (Panthera tigris tigris).
AB  - A laparoscopic-assisted ovariohysterectomy was performed in a 19-year-old intact,
      female Bengal tiger (Panthera tigris tigris) presented for surgical treatment of
      pyometra. A multi-port technique was used with intra-corporeal sealing of the
      ovarian pedicles and extra-corporeal ligation of the uterine vessels and body.
      The tiger recovered from surgery and anesthesia without complication, was
      released into its enclosure the same day, and has remained clinically normal.
      Laparoscopic-assisted ovariohysterectomy may have advantages over open
      ovariohysterectomy for treatment of pyometra in the tiger.

PMID- 30104783
TI  - Modernizing Canada's foot and mouth disease response plan.

PMID- 30104784
TI  - Potentially disabling communication dilemmas.

PMID- 30104785
TI  - Urinary calculi in a shih tzu dog with hyperadrenocorticism.
AB  - An 11-year-old spayed female shih tzu dog was presented with pollakiuria,
      stranguria, and hematuria. Radiographs revealed a large number of radiodense
      urinary calculi within the bladder. Physical examination, complete blood cell
      count, biochemistry and ACTH stimulation test suggested possible
      hyperadrenocorticism. A cystotomy was performed and the patient was treated for
      hyperadrenocorticism.

PMID- 30104788
TI  - Treatment of people diagnosed with chronic hepatitis C virus infection.

PMID- 30104789
TI  - Public health round-up.

PMID- 30104787
TI  - Motorcycle helmet use to reduce road traffic deaths in Thailand.

PMID- 30104790
TI  - Improving the health impacts of airports.
AB  - Airport and aviation authorities are starting to recognize that airports do not
      have to be unhealthy. Sima Barmania reports.

PMID- 30104791
TI  - A human rights approach to mental health and people with disabilities.
AB  - Dainius Puras has devoted the last 30 years to protecting the rights of children
      with mental disabilities and of other vulnerable groups. He talks to Fiona Fleck.

PMID- 30104792
TI  - Patient-led active tuberculosis case-finding in the Democratic Republic of the
      Congo.
AB  - Objective: To investigate the effect of using volunteer screeners in active
      tuberculosis case-finding in South Kivu, the Democratic Republic of the Congo,
      especially among groups at high risk of tuberculosis infection. Methods: To
      identify and screen high-risk groups in remote communities, we trained volunteer
      screeners, mainly those who had themselves received treatment for tuberculosis or
      had a family history of the disease. A non-profit organization was created and
      screeners received training on the disease and its transmission at 3-day
      workshops. Screeners recorded the number of people screened, reporting a
      prolonged cough and who attended a clinic for testing, as well as test results.
      Data were evaluated every quarter during the 3-year period of the intervention
      (2014-2016). Findings: Acceptability of the intervention was high. Volunteers
      screened 650 434 individuals in their communities, 73 418 of whom reported a
      prolonged cough; 50 368 subsequently attended a clinic for tuberculosis testing.
      Tuberculosis was diagnosed in 1 in 151 people screened, costing 0.29 United
      States dollars (US$) per person screened and US$ 44 per person diagnosed.
      Although members of high-risk groups with poorer access to health care
      represented only 5.1% (33 002/650 434) of those screened, they contributed 19.7%
      (845/4300) of tuberculosis diagnoses (1 diagnosis per 39 screened). The
      intervention resulted in an additional 4300 sputum-smear-positive pulmonary
      tuberculosis diagnoses, 42% (4 300/10 247) of the provincial total for that
      period. Conclusion: Patient-led active tuberculosis case-finding represents a
      valuable complement to traditional case-finding, and should be used to assist
      health systems in the elimination of tuberculosis.

PMID- 30104793
TI  - Hypertensive disorders in pregnancy and stillbirth rates: a facility-based study
      in China.
AB  - Objective: To assess the association between hypertensive disorders in pregnancy
      and the stillbirth rate. Methods: We obtained all data from China's National
      Maternal Near Miss Surveillance System for 2012 to 2016. Associations between
      hypertensive disorders in pregnancy and stillbirths, stratified by fetus number
      and gestational age, were assessed using Poisson regression analysis with a
      robust variance estimator. Findings: For the period, 6 970 032 births, including
      66 494 stillbirths, were reported to the surveillance system. The weighted
      stillbirth rate in women with a hypertensive disorder in pregnancy was 21.9 per
      1000 births. The risk was higher in those who had received few antenatal care
      visits or who were poorly educated. For singleton pregnancies, the adjusted risk
      ratio (aRR) for a stillbirth among women with hypertensive disorders in pregnancy
      compared with normotensive women was 3.1 (95% confidence interval, CI: 2.85
      3.37). The aRR for hypertensive disorder subtypes was: 6.66 (95% CI: 5.57-7.96)
      for superimposed preeclampsia; 4.15 (95% CI: 3.81-4.52) for preeclampsia or
      eclampsia; 2.32 (95% CI: 1.87-2.88) for chronic hypertension; and 1.21 (95% CI:
      1.08-1.36) for gestational hypertension. For multiple pregnancies, the
      association between stillbirths and hypertensive disorders in pregnancy was not
      significant, except for superimposed preeclampsia (aRR: 1.95; 95% CI: 1.28-2.97).
      Conclusion: To minimize the incidence of stillbirths, more attention should be
      paid to chronic hypertension and superimposed preeclampsia in singleton
      pregnancies and to superimposed preeclampsia in multiple pregnancies. Better
      quality antenatal care and improved guidelines are needed in China.

PMID- 30104794
TI  - A post-conflict vaccination campaign, Central African Republic.
AB  - Objective: To rapidly increase childhood immunization through a preventive, multi
      antigen, vaccination campaign in Mambere-Kadei prefecture, Central African
      Republic, where a conflict from 2012 to 2015 reduced vaccination coverage.
      Methods: The three-round campaign took place between December 2015 and June 2016
      using: (i) oral poliomyelitis vaccine (OPV); (ii) combined diphtheria, tetanus
      and pertussis (DTP) vaccine, Haemophilus influenza type B (Hib) and hepatitis B
      (DTP-Hib-hepatitis B) vaccine; (iii) pneumococcal conjugate vaccine (PCV); (iv)
      measles vaccine; and (v) yellow fever vaccine. Administrative data were collected
      on vaccines administered by age group and vaccination coverage surveys were
      carried out before and after the campaign. Findings: Overall, 294 054 vaccine
      doses were administered. Vaccination coverage for children aged 6 weeks to 59
      months increased to over 85% for the first doses of OPV, DTP-Hib-hepatitis B
      vaccine and PCV and, in children aged 9 weeks to 59 months, to over  70% for the
      first measles vaccine dose. In children aged 6 weeks to 23 months, coverage of
      the second doses of OPV, DTP-Hib-hepatitis B vaccine and PCV was over 58% and
      coverage of the third doses of OPV and DTP-Hib-hepatitis B vaccine was over 20%.
      Moreover, 61% (5804/9589) of children aged 12 to 23 months had received two PCV
      doses and 90% (25933/28764) aged 24 to 59 months had received one dose.
      Conclusion: A preventive, multi-antigen, vaccination campaign was effective in
      rapidly increasing immunization coverage in a post-conflict setting. To sustain
      high coverage, routine immunization must be reinforced.

PMID- 30104796
TI  - Establishing thresholds and parameters for pandemic influenza severity
      assessment, Australia.
AB  - Objective: To implement the World Health Organization's pandemic influenza
      severity assessment tool in Australia, using multiple sources of data to
      establish thresholds and measure influenza severity indicators. Methods: We used
      data from four reliable sources: sentinel general practitioner surveillance,
      hospital surveillance, a public health hotline and an influenza-like illness
      survey system. We measured three influenza severity indicators (transmissibility,
      impact and disease seriousness) defined using pandemic influenza severity
      assessment guidelines. We used the moving epidemic method and a seriousness
      indicator-specific method to set thresholds for indicator parameters using 2012
      2016 data. We then applied the thresholds to data from the 2017 influenza season.
      Findings: We were able to measure and produce thresholds for each severity
      indicator. At least one laboratory-confirmed influenza parameter was used to
      measure each indicator. When thresholds were applied to the 2017 season, there
      was good agreement across all data sources in measuring activity for each
      indicator. The season was characterized as having high transmissibility and
      extraordinary impact. Seriousness was characterized as moderate overall and in
      all age groups except those aged >= 65 years for whom it was high. This matched
      the description of the season produced by the Australian national influenza
      surveillance committee, based on expert opinion and historical ranges.
      Conclusion: The pandemic influenza severity assessment and moving epidemic method
      provide a robust and flexible method to enable an evidence-based assessment of
      seasonal influenza severity across diverse data sources. This is useful for
      national assessment and will contribute to global monitoring and response to
      circulating influenza with pandemic potential.

PMID- 30104799
TI  - Cluster munitions: military use and civilian health hazards.

PMID- 30104797
TI  - Cost-effectiveness of risk-based breast cancer screening programme, China.
AB  - Objective: To model the cost-effectiveness of a risk-based breast cancer
      screening programme in urban China, launched in 2012, compared with no screening.
      Methods: We developed a Markov model to estimate the lifetime costs and effects,
      in terms of quality-adjusted life years (QALYs), of a breast cancer screening
      programme for high-risk women aged 40-69 years. We derived or adopted age
      specific incidence and transition probability data, assuming a natural history
      progression between the stages of cancer, from other studies. We obtained
      lifetime direct and indirect treatment costs in 2014 United States dollars (US$)
      from surveys of breast cancer patients in 37 Chinese hospitals. To calculate
      QALYs, we derived utility scores from cross-sectional patient surveys. We
      evaluated incremental cost-effectiveness ratios for various scenarios for
      comparison with a willingness-to-pay threshold. Findings: Our baseline model of
      annual screening yielded an incremental cost-effectiveness ratio of US$
      8253/QALY, lower than the willingness-to-pay threshold of US$ 23 050/QALY. One
      way and probabilistic sensitivity analyses demonstrated that the results are
      robust. In the exploration of various scenarios, screening every 3 years is the
      most cost-effective with an incremental cost-effectiveness ratio of US$
      6671/QALY. The cost-effectiveness of the screening is reduced if not all
      diagnosed women seek treatment. Finally, the economic benefit of screening women
      aged 45-69 years with both ultrasound and mammography, compared with mammography
      alone, is uncertain. Conclusion: High-risk population-based breast cancer
      screening is cost-effective compared with no screening.

PMID- 30104795
TI  - Prior caesarean section and likelihood of vaginal birth, 2012-2016, China.
AB  - Objective: To examine the trends and safety of vaginal birth after caesarean
      section around the period of the one-child policy relaxation in China. Methods:
      We used data from China's National Maternal Near Miss Surveillance System between
      2012 and 2016. To examine trends in vaginal birth after caesarean section, we
      used Poisson regression with a robust variance estimator. We also assessed the
      association between vaginal birth after caesarean section and maternal and
      perinatal outcomes. Findings: We analysed 871 636 deliveries by women with a
      previous caesarean section. Both in 2012 and 2016, the rate of vaginal birth
      after caesarean section was 9.8%. After adjusting for institutional,
      sociodemographic and obstetric characteristics, the rate increased by 14% between
      2012 and 2016 (adjusted relative risk, aRR: 1.14; 95% confidence interval, CI:
      1.07-1.21). Compared to women with a repeat caesarean section, women with a
      vaginal birth after caesarean section experienced lower incidence of uterine
      rupture (aRR: 0.26, 95% CI: 0.16-0.42), blood transfusion (aRR: 0.68, 95% CI:
      0.53-0.87) and admission to the intensive care unit (aRR: 0.36, 95% CI: 0.25
      0.52), but higher incidence of intrapartum stillbirths, (aRR: 7.20, 95% CI: 6.09
      8.51), newborns with a 5-minute Apgar score less than 7 (aRR: 1.75, 95% CI: 1.54
      1.99) and neonatal death before discharge (aRR: 1.90, 95% CI: 1.61-2.24).
      Conclusion: Promotion of vaginal birth after caesarean section could increase the
      rate even further in China. To ensure the safety of mothers and their newborns,
      national policies and guidelines on vaginal birth after caesarean section are
      needed.

PMID- 30104798
TI  - Adapting the WHO package of essential noncommunicable disease interventions,
      Samoa.
AB  - Problem: Samoa has been struggling to address the burden of noncommunicable
      diseases at the health system, community and individual levels. Approach: The
      World Health Organization (WHO) package of essential noncommunicable disease
      interventions for primary health care in low-resource settings was adopted in
      seven villages throughout Samoa in 2015. The National Steering Committee Members
      designed and implemented a screening process, and local facilitators and health
      care workers collected health and lifestyle data. The WHO/International Society
      of Hypertension risk assessment was used on villagers older than 40 years to
      identify people at high risk of noncommunicable disease. Local setting: Samoa is
      a small island developing state with increasing morbidity and mortality due to
      noncommunicable diseases. A national representative survey indicated that 50.1%
      (595/1188) of the Samoan adult population is at high risk of such diseases. High
      numbers of noncommunicable diseases are undiagnosed or untreated, because of
      shortage of health-care staff and lack of awareness of risk factors. Relevant
      changes: The teams collected data from 2234 adults. For people older than 40
      years, 6.7% (54/804) were identified as being at high-risk and were encouraged to
      seek treatment or manage risk factors. Community members developed an awareness
      programme to improve understanding of lifestyle risk factors. Lessons learnt:
      Engaging community members was crucial in conducting a successful screening
      campaign. By identifying those villagers at high risk of developing
      noncommunicable diseases, early intervention was possible. Education improved
      awareness of the symptom-free nature of early-stage noncommunicable diseases.

PMID- 30104800
TI  - Global susceptibility and response to noncommunicable diseases.

PMID- 30104801
TI  - Neighborhood sexual violence moderates women's perceived safety in urban
      neighborhoods.
AB  - Perceptions of neighborhood safety are positively associated with perceptions of
      neighborhood violence. However, research has yet to examine whether this
      relationship is moderated by specific types of violence, such as sexual violence,
      that are more salient for women. Using street-intercept interviews with 343
      adults in 9 neighborhoods of a U.S. city with high rates of poverty,
      unemployment, and crime, we examine the relationship of perceived neighborhood
      violence to perceived safety in the context of gender while controlling for
      neighborhood assets that moderate perceptions of neighborhood safety and
      violence. We hypothesized that gender would moderate the relationship between
      perceived neighborhood violence and safety, and that women's perceptions of
      neighborhood safety would be significantly influenced by neighborhood sexual
      violence, but not other types of violence. Although women and men in these high
      crime, urban neighborhoods did not differ in their perceptions of neighborhood
      safety or violence, perceived sexual violence did significantly moderate safety
      by gender; women's perceptions of neighborhood sexual violence predicted
      perceived safety in their neighborhood. Importantly, gender did not moderate
      perceived safety for other types of violence. These results illustrate the
      importance of taking gender and perceived sexual violence into account to
      understand neighborhood safety in adults, particularly women.

PMID- 30104802
TI  - Relationship of hope, sense of community, and quality of life.
AB  - This study examined the role of hope and community in achieving and/or
      maintaining a successful recovery, and their relationships to quality of life for
      individuals in recovery. The sample included 229 participants in 42 Oxford House
      sober living homes in 3 locations in the United States. In this cross-sectional
      investigation, we assessed whether hope and sense of community were predictors of
      quality of life for individuals living in recovery homes. Findings indicated that
      both hope and sense of community were predictors supporting contextual as well as
      individual characteristics as possible influences on recovery trajectories. These
      findings have implications for both individual and systems-level resource or
      competency-based interventions, and they suggest one of the important functions
      of a recovery residence is in the creation of a sense of community.

PMID- 30104803
TI  - Public health and epidemiology of cancer in Colombia.

PMID- 30104804
TI  - High Blood Pressure prevention and control: from evidence to action.

PMID- 30104805
TI  - Perceptions about sexual risk, HIV and HIV-testing in Cali, Colombia.
AB  - Introduction: In Colombia, 20%-54% of the population with sexual practices at
      higher risk for HIV infection (men who have sex with men, transgender women,
      women sex workers) has sometime been tested. Objective: To describe perceptions
      of sexual risk, HIV and HIV testing in people with risky sexual practices and
      people who identify themselves as heterosexual. Methods: Between 2012 and 2014,
      it was carried a descriptive study using HIV screening out in Cali-Colombia with
      the voluntary participation of 940 people aged over 18 years. There were used:
      informed consent, structured questionnaire and HIV testing. Descriptive,
      bivariate and multivariate Poisson regression models were performed. Results:
      Average age 28.5 +/-10.9 years; 50% men. 357 (38%) were people from the
      traditional risk group for HIV infection; and 583 (62%) corresponded to the non
      traditional risk group (heterosexual men and women). Likewise, 62% and 41%
      respectively had HIV test. 51% to 53% reported having sex when they consumed
      liquor; commercial sex was higher in the group with risky sexual practices (32%
      vs 3%), as well as anal relations (77% vs 23%), consistent use of condom (32% vs
      9%), and HIV positive test (14.3% vs 1.6%). The multivariate analysis showed for
      both groups that having HIV test was associated with being older than 25 years
      and a history of sexually transmitted infection. Conclusions: Differentiated
      education strategies are needed based on risky sexual behaviors and that consider
      the importance of regular HIV tests for early diagnosis and timely enrollment in
      care and treatment.

PMID- 30104806
TI  - As-needed endotracheal suctioning protocol vs a routine endotracheal suctioning
      in Pediatric Intensive Care Unit: A randomized controlled trial.
AB  - Objective: To compare two endotracheal suctioning protocols according to
      morbidity, days of mechanical ventilation, length of stay in the Pediatric
      Intensive Care Unit (PICU), incidence of Ventilator-Associated Pneumonia (VAP)
      and mortality. Methods: A Pragmatic randomized controlled trial performed at
      University Hospital Pablo Tobon Uribe, Medellin-Colombia. Forty-five children
      underwent an as-needed endotracheal suctioning protocol and forty five underwent
      a routine endotracheal suctioning protocol. Composite primary end point was the
      presence of hypoxemia, arrhythmias, accidental extubation and heart arrest. A
      logistic function trough generalized estimating equations (GEE) were used to
      calculate the Relative Risk for the main outcome. Results: Characteristics of
      patients were similar between groups. The composite primary end point was found
      in 22 (47%) of intervention group and 25 (55%) children of control group (RR=
      0.84; 95% CI: 0.56-1.25), as well in 35 (5.8%) of 606 endotracheal suctioning
      performed to intervention group and 48 (7.4%) of 649 performed to control group
      (OR= 0.80; 95% CI: 0.5-1.3). Conclusions: There were no differences between an as
      needed and a routine endotracheal suctioning protocol. Trial registration:
      ClinicalTrials.gov identifier NCT01069185.

PMID- 30104807
TI  - Development and validation of anthropometric equations to estimate body
      composition in adult women.
AB  - Objective: To develop anthropometric equations to predict body fat percentage
      (BF%). Methods: In 151 women (aged 18-59) body weight, height, eight- skinfold
      thickness (STs), six- circumferences (CIs), and BF% by hydrodensitometry were
      measured. Subjects data were randomly divided in two groups, equation-building
      group (n= 106) and validation group (n= 45). The equation-building group was used
      to run linear regression models using anthropometric measurements as predictors
      to find the best prediction equations of the BF%. The validation group was used
      to compare the performance of the new equations with those of Durnin-Womersley,
      Jackson-Pollock and Ramirez-Torun. Results: There were two preferred equations:
      Equation 1= 11.76 + (0.324 x tricipital ST) + (0.133 x calf ST) + (0.347 x
      abdomen CI) + (0.068 x age) - (0.135 x height) and Equation 2= 11.37 + (0.404 x
      tricipital ST) + (0.153 x axilar ST) + (0.264 x abdomen CI) + (0.069 x age) -
      (0.099 x height). There were no significant differences in BF% obtained by
      hydrodensitometry (31.5 +/-5.3) and Equation 1 (31.0 +/-4.0) and Equation 2 (31.2
      +/-4.0). The BF% estimated by Durning-Womersley (35.8 +/-4.0), Jackson-Pollock
      (26.5 +/-5.4) and Ramirez-Torun (32.6 +/-4.8) differed from hydrodensitometry (p
      <0.05). The interclass correlation coefficient (ICC) was high between
      hydrodensitometry and Equation 1 (ICC= 0.77), Equation 2 (ICC= 0.76), and Ramirez
      Torun equation (ICC= 0.75). The ICC was low between hydrodensitometry and Durnin
      Womersley (ICC= 0.51) and Jackson-Pollock (ICC= 0.53) equations. Conclusion: The
      new Equations-1 and 2, performed better than the commonly used anthropometric
      equations to predict BF% in adult women.

PMID- 30104809
TI  - Netrin 1 and Alpha-Methyl Acylcoenzim-A Racemase in diagnosis of prostate cancer.
AB  - Objectives: To investigate serum and urine levels of Alpha-methylacyl-CoA
      racemase (AMACR) and Netrin 1 in patients with and without prostate cancer and to
      determine whether these markers could be used as alternatives in diagnosis of
      prostate cancer instead of serum prostate specific antigen (PSA) levels. Methods:
      One hundred and seventy five patients between 45-75 years to whom transrectal
      ultrasound guided biopsies were performed for abnormal serum PSA levels or
      digital rectal examinations were included. The levels of AMACR and Netrin 1
      levels of blood and urine samples of 5 mL those were taken prior to biopsies were
      measured. . Results: The mean age of the patients was 62.7 +/-6.4 years. Prostate
      cancer was detected in 40 patients (22.8%) while 135 of them (77.2%) were
      diagnosed as benign prostate hyperplasia (BPH). In BPH group, serum and urine
      levels of AMACR and Netrin 1 were 13.4 +/-16.9 ng/mL; 7.1 +/-3.4 ng/mL; 164.1+/
      46 pg/mL and 19.5 +/-5.0 pg/mL respectively. The levels of serum and urine levels
      of AMACR and Netrin 1 were 10.2 +/-9.8 ng/mL; 6.8 +/-2.5 ng/mL; 159.1 +/-44.1
      pg/mL and 20.1 +/-5.3 pg/mL respectively in prostate cancer group. There was no
      statistically significant difference or correlation between these two groups
      serum and urine AMACR and Netrin 1 results. Conclusions: Serum and urine levels
      of AMACR and Netrin 1 were not found to be alternatives for serum PSA levels in
      the diagnosis of prostate cancer in this study.

PMID- 30104808
TI  - A study of community-acquired Mycoplasma pneumoniae in Yantai, China.
AB  - Introduction: Community-acquired pneumonia (CAP) is a global disease responsible
      for a large number of deaths, with significant economic impact. As diagnostic
      tools have increased in sensitivity, understanding of the etiology of CAP has
      begun to change. Mycoplasma pneumoniae is one of the major pathogens causing CAP.
      Macrolides and related antibiotics are first-line treatments for M. pneumoniae.
      Macrolide resistance has been spreading for 15 years and now occurs in worldwide.
      We undertook the first study on macrolide resistance of M. pneumoniae in Yantai.
      This may be helpful to determine the appropriate therapy for CAP in this
      population. Objective: To investigate the rate and mechanism of macrolide
      resistance in Yantai. Methods: Pharyngeal swab samples were collected from adult
      CAP patients. Samples were assayed by polymerase chain reaction (PCR) and
      cultivated to test for M. pneumoniae. Nested PCR was used to specifically amplify
      M. pneumoniae 23S rRNA gene fragments containing mutations, and amplicons were
      analyzed by CE-SSCP for macrolide resistance mutations. Results were confirmed by
      sequencing. Twenty-seven strains of M. pneumoniae were isolated and the
      activities of nine antibiotics against M. pneumoniae were tested in vitro.
      Results: Out of 128 samples tested, 27 were positive for M. pneumoniae.
      Mycoplasma 100% macrolides resistance to Mycoplasma pneumoniae. The mechanism of
      macrolides resistance was A2063G point mutation in the sequence directly binding
      to macrolides in the 23S rRNA V domain in vitro. The mean pyretolytic time for
      the fluoroquinolone group was 4.7 +/-2.9 d, which was significantly shorter than
      8.2 +/-4.1 d for the azithromycin group. Conclusions: Macrolides are not the
      first-line treatment for M. pneumoniae respiratory tract infections in Yantai.

PMID- 30104810
TI  - Clinical differences between children with asthma and rhinitis in rural and urban
      areas.
AB  - Background: Epidemiological studies have shown that children who grow up on
      traditional farms are protected from allergic diseases. However, less is known
      about if the environment influences the pharmacotherapy in these patients.
      Objective: To compare the treatment of asthmatic and rhinitis children from urban
      and rural areas in Medellin, Colombia. Methods: During one year, we follow up a
      group of children (6 to 14 years) with diagnostic of asthma or rhinitis living
      for more than five years in urban or rural area. A questionnaire with socio
      demographic characteristics, pharmacotherapy treatments, was obtained each three
      months. Atopy evaluation, spirometry and clinical test for asthma and rhinitis
      severity were done at the beginning and one year later. Results: Eighty six point
      four percent patients completed the follow up (rural n: 134, urban n: 248).
      Patients in rural location required less salbutamol (p: 0.01), visit to emergency
      department (p <0.01) and have a less number of patients with FEV1 <80% (p: 0.05).
      For clinical control rural children require less pharmacotherapy than urban
      children (p: 0.01) and more patients with rhinitis (18% vs 8% p: 0.03) and asthma
      (23% vs 12% p: 0.01) in the rural group could suspended pharmacotherapy. Atopy
      (p: <0.07) and poli-sensitization (p: <0.08) was a little higher in urban than
      rural area. We observe that poverty/unhygienic indicators were risk factors for
      higher levels of specific IgE among patients from urban area. Conclusion:
      Patients with respiratory allergies located in urban area require more
      pharmacotherapy and have less clinical response than rural children.

PMID- 30104811
TI  - Reevaluating nutrition as a risk factor for cardio-metabolic diseases.
AB  - Introduction: The consumption of saturated fats is considered a risk factor for
      cardiovascular diseases. Objective: Review published papers on the role of macro
      nutrient intake in cardiovascular risk. Results: Recent reports from the PURE
      study and several previous meta-analyses, show that the consumption of total
      saturated and unsaturated fat is not associated with risk of acute myocardial
      infarction or mortality due to cardiovascular disease. High carbohydrate intake
      was associated with the highest risk of total and cardiovascular mortality, while
      total fat consumption or of its different types was associated with a lower risk
      of mortality. A high consumption of fruits, vegetables and legumes was associated
      with lower risk of total mortality and non-cardiovascular mortality. The
      consumption of 100 g of legumes, two or three times a week, ameliorated
      deficiencies of the nutrients contained in these foods and was associated with a
      reduction in the risk of developing chronic non-communicable diseases.
      Conclusion: A healthy diet should be balanced and varied, be composed of a
      proportion of complex carbohydrates rich in fibber between 50-55% of the daily
      energy consumed, of saturated and unsaturated fat (25-30%), animal and vegetable
      protein (including legumes) between 15-25%, vitamins, minerals and water. These
      nutrients are abundantly present in fruits, vegetables, cereals, legumes, milk
      and its derivatives, eggs and meats, so public policies should promote the
      availability and access to these nutrients within primary prevention programs to
      reduce the growing prevalence of cardio-metabolic diseases.

PMID- 30104813
TI  - Erratum: Cali Cancer Registry Methods.
AB  - [This corrects the article on p. 109-120 in vol. 49, PMID: 29983471.].

PMID- 30104812
TI  - Clinical and mutational spectrum of Colombian patients with Pelizaeus Merzbacher
      Disease.
AB  - Case Presentation: Pelizaeus Merzbacher Disease (PMD) is an X-linked
      developmental defect of myelination that causes childhood chronic spastic
      encephalopathy. Its genetic etiology can be either a duplication (or other gene
      dosage alterations) or a punctual mutation at the PLP1 locus. Clinically, it
      presents with developmental delay, nystagmus and, spasticity, supported by
      neuroimaging in which the defect of myelination is evident. We present a series
      of seven Colombian patients diagnosed with this leucodystrophy, describing their
      genotypic and phenotypic characteristics and heterogeneity. Clinical Findings:
      All patients included were male, 6 months to 16 years of age. Mean age at onset
      of symptoms was 8 months. Mean age at diagnosis was 5 years 5 months, being
      classic PMD most frequently diagnosed, as compared to the connatal phenotype. All
      cases had a primary diagnosis of developmental delay on 100%, and in 28.7% of
      cases, early onset nystagmus was described. 85.7% of patients had spasticity,
      71.4% cerebellar signs, 57.0% hypotonia, and 28.5% had an abnormal movement
      disorder. Only three patients were able to achieve gait, though altered. In the
      two patients who had a diagnosis of connatal PMD maturational ages in danger
      zones according to the WHO Abbreviated Scale of Psychosocial Development were
      documented. All cases had abnormalities in neuroimages. Molecular Analysis and
      Results: Molecular studies were used in the majority of the cases to confirm the
      diagnosis (85.7 %). For two cases molecular confirmation was not considered
      necessary given their affected male brothers had already been tested. PLP1 gene
      dosage alterations (duplications) were found in 28.5 % of the patients (two
      siblings), whereas three different single nucleotide variants were detected.
      Clinical Relevance: According to these findings, as authors we propose the
      diagnostic algorithm in Colombian population to begin on a high clinical
      suspicion, followed by paraclinical extension, moving on to the molecular
      confirmation by using approaches to simultaneously sequence the PLP1 gene in
      order to detect point mutations and in/dels and performing a copy number
      variation analysis for the detection of gene dosage alterations.

PMID- 30104815
TI  - Receptiveness to advice, cognitive ability, and technology adoption?.
AB  - We construct a model of technology adoption with agents differing on two
      dimensions: their cognitive ability and their receptiveness to advice. While
      cognitive ability unambiguously speeds adoption, receptiveness to advice may
      speed adoption for individuals with low cognitive ability, but slow adoption for
      individuals with high cognitive ability. We conduct economic experiments
      measuring US farmers' cognitive ability and receptiveness to advice and examine
      how these characteristics impact their speed of adoption of genetically modified
      (GM) corn seeds. The empirical analysis shows that early adopters are those who
      are both quite able cognitively and not receptive to advice.

PMID- 30104816
TI  - Erratum: The Application of the International Classification of Functioning,
      Disability and Health to Functional Auditory Consequences of Mild Traumatic Brain
      Injury.
AB  - [This corrects the article DOI: 10.1055/s-0036-1584409.].

PMID- 30104814
TI  - Cyclins in aspergilli: Phylogenetic and functional analyses of group I cyclins.
AB  - We have identified the cyclin domain-containing proteins encoded by the genomes
      of 17 species of Aspergillus as well as 15 members of other genera of filamentous
      ascomycetes. Phylogenetic analyses reveal that the cyclins fall into three
      groups, as in other eukaryotic phyla, and, more significantly, that they are
      remarkably conserved in these fungi. All 32 species examined, for example, have
      three group I cyclins, cyclins that are particularly important because they
      regulate the cell cycle, and these are highly conserved. Within the group I
      cyclins there are three distinct clades, and each fungus has a single member of
      each clade. These findings are in marked contrast to the yeasts Saccharomyces
      cerevisiae, Schizosaccharomyces pombe, and Candida albicans, which have more
      numerous group I cyclins. These results indicate that findings on cyclin function
      made with a model Aspergillus species, such as A. nidulans, are likely to apply
      to other Aspergilli and be informative for a broad range of filamentous
      ascomycetes. In this regard, we note that the functions of only one Aspergillus
      group I cyclin have been analysed (NimECyclin B of A. nidulans). We have
      consequently carried out an analysis of the members of the other two clades using
      A. nidulans as our model. We have found that one of these cyclins, PucA, is
      essential, but deletion of PucA in a strain carrying a deletion of CdhA, an
      activator of the anaphase promoting complex/cyclosome (APC/C), is not lethal.
      These data, coupled with data from heterokaryon rescue experiments, indicate that
      PucA is an essential G1/S cyclin that is required for the inactivation of the
      APC/C-CdhA, which, in turn, allows the initiation of the S phase of the cell
      cycle. Our data also reveal that PucA has additional, non-essential, roles in the
      cell cycle in interphase. The A. nidulans member of the third clade (AN2137) has
      not previously been named or analyzed. We designate this gene clbA. ClbA
      localizes to kinetochores from mid G2 until just prior to chromosomal
      condensation. Deletion of clbA does not affect viability. However, by using a
      regulatable promoter system new to Aspergillus, we have found that expression of
      a version of ClbA in which the destruction box sequences have been removed is
      lethal and causes a mitotic arrest and a high frequency of non-disjunction. Thus,
      although ClbA is not essential, its timely destruction is essential for
      viability, chromosomal disjunction, and successful completion of mitosis.

PMID- 30104817
TI  - Two-scale dispersal estimation for biological invasions via synthetic likelihood.
AB  - Biological invasions reshape environments and affect the ecological and economic
      welfare of states and communities. Such invasions advance on multiple spatial
      scales, complicating their control. When modeling stochastic dispersal processes,
      intractable likelihoods and autocorrelated data complicate parameter estimation.
      As with other approaches, the recent synthetic likelihood framework for
      stochastic models uses summary statistics to reduce this complexity; however, it
      additionally provides usable likelihoods, facilitating the use of existing
      likelihood-based machinery. Here, we extend this framework to parameterize multi
      scale spatio-temporal dispersal models and compare existing and newly developed
      spatial summary statistics to characterize dispersal patterns. We provide general
      methods to evaluate potential summary statistics and present a fitting procedure
      that accurately estimates dispersal parameters on simulated data. Finally, we
      apply our methods to quantify the short and long range dispersal of Chagas
      disease vectors in urban Arequipa, Peru, and assess the feasibility of a purely
      reactive strategy to contain the invasion.

PMID- 30104818
TI  - Abusive culture in medical education: Mentors must mend their ways.

PMID- 30104819
TI  - Role of anesthesiologist in ex utero intrapartum treatment procedure: A case and
      review of anesthetic management.
AB  - The ex utero intrapartum treatment (EXIT) procedure is a rare form of perinatal
      resuscitation. It is basically a bridge therapy between partial delivery of the
      child and stabilization of its cardiorespiratory functions. This procedure has
      multiple anesthetic challenges including maternal anesthesia, maintenance of
      uteroplacental flow, tocolysis till the neonate is stabilized, management of
      postpartum hemorrhage, fetal, and neonatal anesthesia. This review also describes
      a case of cervical teratoma in fetus, for which the EXIT was performed in our
      institute. In addition to the case description, multiple concerns specific for
      EXIT procedure are discussed in this review.

PMID- 30104821
TI  - Heart failure with preserved ejection fraction (HFpEF): Implications for the
      anesthesiologists.
AB  - Heart failure (HF) is a complex clinical syndrome that results from any
      structural or functional impairment of ventricular filling or ejection of blood.
      American College of Cardiology Foundation / American Heart Association 2013
      guidelines have classified HF into two categories: (i) HF with reduced (<=40%)
      ejection fraction (HFrEF) or systolic HF, and (ii) HF with preserved (>=50%)
      ejection fraction (HFpEF) or diastolic HF. Risk factors for HFpEF include age
      more than 70 years, female gender, hypertension, wide pulse pressure, diabetes
      mellitus, chronic renal insufficiency, left ventricular hypertrophy, atrial
      fibrillation, smoking, recent weight gain, and exercise intolerance. Cardiac
      catheterization and echocardiography are used for the confirmation of diagnosis
      of HFpEF. Intraoperatively, the hemodynamic goals in patients with HFpEF are
      avoidance of tachycardia, maintenance of sinus rhythm, and maintenance of higher
      than usual filling pressure. No specific treatment for HFpEF is established, and
      therapeutic options include an intravenous diuretic, a beta blocker or calcium
      channel blocker, a venodilator, and management of co-morbidities.

PMID- 30104823
TI  - The choice of the hypnotic drug (volatile or propofol) for maintenance of
      anesthesia does not influence surgical conditions during cranioplasty.
AB  - Background and Aims: In contrast to propofol, volatile agents are often
      considered harmful to maintain anesthesia due to increasing brain volume and
      potential deleterious effects. Patients for cranioplasty, including patients with
      large bone defects, could be susceptible for intraoperative complications but
      have not properly been investigated so far. The aim of the present study was to
      evaluate brain swelling, intraoperative conditions, surgical course, and
      postoperative complication rates of propofol-based vs. volatile-based anesthesia.
      Material and Methods: In this monocentric, retrospective, and observational
      study, we collected demographic, clinical, and outcome data of patients
      undergoing cranioplasty between December 2010 and September 2014. According to
      the hypnotic drug used, patients were assigned to either a propofol or a volatile
      group. The primary outcome parameter was brain swelling. For comparison of the
      groups, univariate analysis was performed using Chi-square and Mann-Whitney-U
      test. Results: One hundred and one patients were identified in the period. Twenty
      three patients were excluded due to cerebrospinal fluid diversion. Baseline
      characteristics and preoperative conditions did not vary between the groups
      except a higher body mass index and positive end-expiratory pressure (PEEP) in
      the propofol group. The choice of anesthesia (volatile or intravenous) influence
      neither the intraoperative local conditions nor postoperative complication rate.
      No significant risk factor for impaired bone flap placement was identified.
      Conclusions: In a well-defined cohort, the choice of the anesthetic agent does
      not influence the degree of intraoperative brain swelling, bone flap fit, and
      postoperative course.

PMID- 30104820
TI  - Pharmacogenomics of analgesics in anesthesia practice: A current update of
      literature.
AB  - The field of pharmacogenomics seeks to understand how an individual's unique gene
      sequence can affect their response to certain drugs. It is particularly relevant
      in anesthesia when the interindividual response to pain medication is essential.
      Codeine and tramadol are prodrugs metabolized by CYP2D6, polymorphisms of which
      can cause dangerous or even fatal levels of their metabolites, or decrease the
      level of metabolites to decrease their analgesic effect. Many other opioids are
      metabolized by CYP2D6 or CYP3A5, of which loss-of-function variants can cause
      dangerous levels of these drugs. The OCT1 transporter facilitates the movement of
      drugs into hepatocytes for metabolism, and variants of this transporter can
      increase serum levels of morphine and O-desmethyltramadol. Many NSAIDs are
      metabolized by CYP2C9, and there is concern that variants of this enzyme may lead
      to high serum levels of these drugs, causing gastrointestinal bleeding, however
      the data does not strongly support this. The ABCB1 gene encodes for P
      glycoprotein which facilitates efflux of opioids away from their target
      receptors. The C3435T SNP may increase the concentration of opioids at target
      receptors, although the data is not conclusive. Catechol-O-Methyltransferase
      (COMT) is shown to indirectly upregulate opioid receptors. Certain haplotypes of
      COMT have been demonstrated to have an effect on opioid requirements. The OPRM1
      gene codes for the mu-opioid receptor, and there is conflicting data regarding
      its effect on analgesia and opioid requirements. Overall, there is a fair amount
      of conflicting data in the above topics, suggesting that there is still a lot of
      research to be done on these topics, and that pain perception is multifactorial,
      likely including many common genetic variants.

PMID- 30104822
TI  - Thoracic paravertebral block for the anesthetic management of percutaneous
      radiofrequency ablation of liver tumors.
AB  - Background and Aims: Percutaneous radiofrequency ablation (PRFA) is a minimally
      invasive treatment for hepatic tumors. We assessed and compared the efficacy of
      right thoracic paravertebral block (TPVB) with that of local anesthetic
      infiltration for the anesthetic management of PRFA of liver tumors. Material and
      Methods: Sixty patients with hepatic tumors aged 50-80 years were randomly
      allocated into two groups. Group I received local anesthetic infiltration along
      the path of the ablation device with sedation. Group II received right TPVB at
      the level T7 and T9 with sedation. The pain was assessed using visual analog
      scale (VAS) at 1 min and then every 5 min during PRFA procedure, on admission,
      and discharge from the post-PRFA observation area. The total dose of rescue
      analgesia during PRFA procedure, number of patients requiring general anesthesia,
      patient and radiologist satisfaction were reported. Results: VAS was
      significantly lower in group II than group I during and after PRFA procedure (P <
      0.05). General anesthesia was administered in 7 patients in group I, whereas no
      patient required general anesthesia in group II (P < 0.05). Patient and
      radiologist satisfaction were significantly higher in group II compared to group
      I (P < 0.05). There were no significant complications in group II compared to
      group I (P > 0.05). Conclusions: Right TPVB with sedation is an effective and
      safe anesthetic technique for the management of PRFA procedure of hepatic tumors.
      It is more effective than local anesthesia with sedation in relieving pain during
      PRFA procedure of hepatic tumors.

PMID- 30104824
TI  - Evaluation of volatile and intravenous anesthetics, effects on the threshold of
      neuroresponse telemetry and the threshold of acoustically evoked stapedial reflex
      in children undergoing cochlear implant surgery.
AB  - Background and Aims: Congenital hearing loss affects about 1 in every 1000 live
      births. Cochlear implant is an effective therapeutic method for aural
      rehabilitation in children suffering from severe-to-profound hearing loss. The
      aim of this study was to compare the effects of the intravenous and inhalational
      anesthesia techniques on neuroauditory threshold and stapedial reflex threshold
      responses. Material and Methods: After approval of the university ethics
      committee and obtaining written informed parental consent, 110 children with
      severe or profound bilateral sensorineural hearing loss undergoing cochlear
      implant surgery were randomly divided in two groups. The effects of the total
      intravenous anesthesia (propofol and remifentanil) and inhalation anesthesia
      (sevoflurane) techniques were evaluated on the neuroauditory threshold and
      stapedial reflex threshold responses of patients. Variations in systolic and
      diastolic blood pressures and mean arterial blood pressure were measured in both
      groups. Results: No significant difference was observed in the following
      parameters: age, weight, duration of anesthesia, and surgery. No side effects was
      observed in the two groups. No significant difference was found in the Telemetry
      Neuroal Response Test (TNRT) reflex between the two groups (P = 0.294); however,
      the difference between the two groups was significant (P = 0.001) for Electrical
      Stapedial Reflex Threshold (ESRT) reflex. In the sevoflurane group, in 39
      patients in the electrode 3 and in 17 patients in the electrode 9 (compared with
      20 and 6 patients in the Propofol-remifentanil group) complete suppression of
      stapedial reflex existed. Conclusion: Our results suggest that, during the
      cochlear implant surgery, use of inhalation anesthetics should be avoided for
      achieving controlled hypotension because this may suppress or even fully
      eliminate stapedial reflex. Remifentanil and Propofol infusion has a slight
      effect on hearing thresholds and is recommended for determining hearing
      thresholds during cochlear implant surgeries.

PMID- 30104825
TI  - A comparison between the Supreme laryngeal mask airway and the laryngeal tube
      suction during spontaneous ventilation: A randomized prospective study.
AB  - Background and Aims: The Supreme laryngeal mask airway (SLMA) and the laryngeal
      tube suction-disposable (LTS-D), both second-generation supraglottic airway
      devices, have a record of efficiency when used for airway management in
      mechanically ventilated patients, during general anesthesia. There is no
      published data comparing these two devices in patients breathing spontaneously
      during general anesthesia. Material and Methods: Eighty patients with normal
      airways undergoing elective general anesthesia with spontaneous ventilation were
      randomized to airway management with a SLMA or LTS-D. Efficacy and adequacy of
      oxygenation and ventilation were compared. Results: No cases of desaturation of
      oxygen saturation (SpO2) values of less than 95% occurred with either device. The
      mean difference for SpO2 between the two devices (0.7%) has no clinical
      significance. Slight hypercapnia was noted with both devices to acceptable values
      during spontaneous ventilation. Conclusions: Both SLMA and LTS-D are suitable and
      effective for airway management in patients breathing spontaneously during
      general anesthesia for minor surgery of short duration.

PMID- 30104826
TI  - Comparison of laryngeal mask airway CTrachTM and Airtraq(r) videolaryngoscopes as
      conduits for endotracheal intubation in patients with simulated limitation of
      cervical spine movements by manual in-line stabilization.
AB  - Background and Aims: Laryngeal mask airway (LMA) CTrachTM and Airtraq(r)
      videolaryngoscopes are useful for endotracheal intubation in patients with
      limited cervical spine movements and other predicted difficult airways. We aimed
      to compare LMA CTrachTM and Airtraq(r) videolaryngoscopes as conduits for
      endotracheal intubation in patients with simulated limitation of cervical spine
      movements by manual in-line stabilization (MILS). Material and Methods: This was
      a prospective, randomized study including 50 patients undergoing elective
      surgeries under general anesthesia. Patients were assigned to undergo intubation
      using Airtraq(r) (n = 25) or LMA CTrachTM (n = 25) by an experienced
      anesthesiologist, while MILS was provided. Laryngoscopy and intubation were
      compared in terms of time taken to obtain optimal laryngeal view, successful
      intubation, total time, percentage of glottis opening (POGO) score, maneuvers
      required for optimal laryngeal view and alignment of endotracheal tube, and
      number of attempts and complications. An integrated score was calculated to
      classify the attempt as good, restricted, or poor. Results: Time taken to obtain
      optimal laryngeal view, successful intubation, and total time in both groups were
      comparable. POGO score >50% was seen in 25 and 21 patients in Groups A and C.
      Seventy-six percent and ninety-six percent in Groups A and C, respectively, had a
      good integrated score; 6% and 1% had restricted score; none had a poor score; and
      the difference between them was statistically significant (P = 0.042).
      Conclusions: LMA CTrachTM and Airtraq(r) are similar with respect to time taken
      for obtaining optimal laryngeal view, successful intubation, and total time when
      used for intubation in patients with simulated limitation of cervical spine
      movements.

PMID- 30104828
TI  - Hyponatremia: A role for vasopressin receptor antagonists?

PMID- 30104827
TI  - Efficacy of vaptans for correction of postoperative hyponatremia: A comparison
      between single intravenous bolus conivaptan vs oral tolvaptan.
AB  - Background and Aims: Hyponatremia is one of the most common electrolyte
      abnormality encountered in postoperative patients especially in the elderly. We
      aimed to assess the efficacy of single-dose intravenous conivaptan vs. oral
      tolvaptan therapy for correction of hyponatremia in postoperative patients.
      Material and Methods: This prospective randomized study was conducted on 40
      patients aged 20-70 years, who had undergone major head and neck surgeries with a
      serum sodium level of <=130 mEq/L and were symptomatic. Patients were randomly
      allocated into two equal groups. Patients belonging to group C received single
      intravenous bolus dose of conivaptan 20mg, whereas group T received oral
      tolvaptan 15mg on the first day. At 24h, if sodium correction was <4mEq/L, dose
      of tolvaptan was increased to 30mg in group T or an infusion of conivaptan 20mg
      over next 24h was started in group C. Results: Chi-square test, independent
      sample t-test, and paired t-test were used as applicable. Though there was no
      significant difference in the baseline sodium values in both groups, at 12 and 24
      h group C had significantly high values. At 48h sodium values in both the groups
      were comparable. Intra-group analysis had shown that there was a significant
      increase in sodium values from the baseline at 12, 24, and 48 h in both the
      groups. Conclusion: Single-dose intravenous conivaptan as well as oral tolvaptan
      were safe and effective in correcting hyponatremia in postoperative patients.
      Conivaptan could be considered superior as it resulted in faster sodium
      correction with effective aquaresis.

PMID- 30104829
TI  - Nalbuphine pretreatment for prevention of etomidate induced myoclonus: A
      prospective, randomized and double-blind study.
AB  - Background and Aims: Etomidate induced myoclonus (EM) is a common and hazardous
      sequel. Premedication with a number of opioids has been shown to effectively
      attenuate EM. However, there is no reported literature evaluating the effect of
      nalbuphine pretreatment on EM. The present study was designed to evaluate the
      efficacy of 0.2 mg/kg nalbuphine intravenous (IV) pretreatment for prevention of
      EM. Material and Methods: This prospective randomized double-blind and placebo
      controlled study was conducted in a medical college associated tertiary hospital.
      One hundred patients undergoing elective surgeries under general anesthesia were
      randomly allocated to one of two groups to receive: 10 ml of normal saline (Group
      I) or 0.2 mg/kg nalbuphine in 10 ml of normal saline (Group II) 150 s before
      injection etomidate 0.3 mg/kg administered IV over 20 s. The patients were
      assessed for the presence and severity of etomidate induced vascular pain (EP)
      and EM while injecting etomidate and for the next 2 min, respectively. The
      patients were monitored for sedation, nausea/vomiting, headache, dizziness, and
      respiratory depression for 24 h postoperatively. Student's t-test, Chi-square
      test, or Fisher exact test were used wherever appropriate and P < 0.05 was
      considered statistically significant. Results and Conclusion: Both the groups
      were comparable with respect to demographic characteristics. Nalbuphine
      pretreatment significantly reduced the incidence (20% vs. 72%; respiratory rate =
      0.294, 95% confidence interval: 0.160-0.496, P < 0.01) and severity of EM without
      any significant increase in the incidence of adverse effects. Nalbuphine 0.2
      mg/kg IV pretreatment significantly reduces the incidence and severity of EM with
      side-effect profile comparable to saline placebo.

PMID- 30104830
TI  - Comparison of dermatomal sensory block following ultrasound-guided transversus
      abdominis plane block by the lateral and posterior approaches: A randomized
      controlled trial.
AB  - Background and Aims: Ultrasound (US)-guided transversus abdominis plane (TAP)
      block is used as a part of a multimodal analgesic regimen in the postoperative
      period. Lateral approach TAP block (LTAP) has been widely used for postoperative
      analgesia after lower abdominal surgeries. Posterior approach TAP block (PTAP),
      which is achieved by more posterior blockade of the anterior ramus of the spinal
      nerve, also provides profound postoperative analgesia after transverse lower
      abdominal incision. We investigated the dermatomal sensory block following LTAP
      and PTAP under US guidance. Material and Methods: Twenty-seven adult female
      patients undergoing the laparoscopic resection of ovarian tumors under general
      anesthesia were randomly divided into two groups, those receiving LTAP (Group L,
      n = 14) and those receiving PTAP (Group P, n = 13). Before induction of general
      anesthesia, all patients were given bilateral TAP blocks with 15 ml of 0.25%
      levobupivacaine on each side under US guidance, and the sensory blockade was
      evaluated. Results: The data are expressed as median (interquartile range [IQR]).
      PTAP produced a median sensory blockade to sharp touch of three dermatomal
      segments (IQR 3-4), the most cephalad being T-10 (IQR T-9-T-10), whereas LTAP
      produced blockade of a median of two segments (IQR 2-2, P = 0.002), the most
      cephalad being T-10 (IQR T-10-T-10, P = 0.005). Conclusions: PTAP produced a
      sensory block that involved a greater number of dermatomes and involvement of
      more cephalad dermatome blocked to sharp touch, compared with LTAP under US
      guidance.

PMID- 30104831
TI  - Dexmedetomidine for prevention of early postoperative catheter-related bladder
      discomfort in voluntary kidney donors: Prospective, randomized, double-blind,
      placebo-controlled trial.
AB  - Background and Aims: Catheter-related bladder discomfort (CRBD) has started to
      gain recognition as a problem in early postoperative care. Dexmedetomidine
      reduces bladder contractility via M3 muscarinic receptor antagonism and alpha-2
      receptor agonism, apart from its concomitant therapeutic benefits, such as
      sedation and sympatholysis, in a postoperative period. We, therefore, evaluated
      the efficacy of dexmedetomidine in reducing incidence and severity of CRBD.
      Material and Methods: This prospective, randomized, double-blind, placebo
      controlled trial done on 110 voluntary kidney donors for live related kidney
      transplantations were planned for laparoscopic donor nephrectomy. The donors were
      of ages 18-60 years, American Society of Anesthesiologists physical status I and
      II of either sex. The control group received 20 ml normal saline (NS) intravenous
      (IV) infusion over 15 min, whereas the dexmedetomidine group received
      dexmedetomidine 1 MUg/kg made in 20 ml NS as IV infusion over 15 min. The
      incidence and severity of CRBD were recorded as primary endpoints up to 12 h in
      early postoperative period. The incidence of bladder discomfort was analysed by
      Fisher's exact test and severity of bladder discomfort by Mann Whitney U test.
      Results: The incidence of CRBD on arrival at postoperative care unit was 18% in
      dexmedetomidine group compared to 42% in control group (P < 0.05). The incidence
      and severity of CRBD reduced in dexmedetomidine group at 0, 2, and 4 h compared
      with control group (P < 0.05). Conclusions: Dexmedetomidine 1 MUg/kg administered
      IV to patients 30 min before extubation reduces the incidence and severity of
      CRBD in early postoperative settings with no adverse effects.

PMID- 30104832
TI  - Transcutaneous nerve stimulation for pain relief during chest tube removal
      following cardiac surgery.
AB  - Background and Aims: In patients undergoing open heart surgery, chest tubes are
      removed postoperatively when patients are well awake and stable. Pain during
      chest tube removal can be moderate to severe and can be the worst experience of
      hospitalization. Various modalities of pain relief during chest tube removal have
      been tried with variable results. We sought to examine the effect of
      transcutaneous electrical nerve stimulation (TENS) as an intervention for pain
      relief during chest tube removal after cardiac surgery. Material and Methods: In
      a tertiary care center, fifty patients undergoing open heart surgery were
      randomized into two groups. Group TENS (n = 25) received TENS from 30 min before
      and continued up to 30 min after chest tube removal. Control Group (n = 25) did
      not receive TENS. In both the groups, additional analgesic medication was
      provided on demand, besides the standard analgesic regime which was injection
      ketorolac 30 mg intramuscularly every 8 h. Patients were studied for pain during
      chest drain removal and pain related nausea, vomiting, and sense of well-being.
      Results: Mean visual analog pain score assessed for chest tube removal was
      significantly less 4.1 +/- 1.2 (P < 0.05) in TENS Group as compared to 6.1 +/-
      0.8 in Control Group. Significantly greater number of patients (n = 14) (P <
      0.05) in Control Group demanded additional analgesia as compared to TENS Group (n
      = 5). Feeling of well-being, improvement in appetite, and sleep was better in
      TENS Group as compared to Control Group. Conclusion: We conclude that TENS might
      not replace the conventional analgesics but has definite adjuvant role in
      decreasing pain scores and improves sense of well-being during chest tube removal
      after cardiac surgery.

PMID- 30104833
TI  - A double-blind randomized control trial to compare the effect of varying doses of
      intrathecal fentanyl on clinical efficacy and side effects in parturients
      undergoing cesarean section.
AB  - Background and Aims: It is a common practice to add intrathecal lipophilic
      opioids to local anesthetics to improve the quality of subarachnoid block. This
      study was designed to find a dose of intrathecal fentanyl, which can improve the
      quality of surgical anesthesia with minimal side effects in parturients
      undergoing cesarean section under spinal anesthesia with intrathecal bupivacaine.
      Material and Methods: In a prospective randomized double-blind study, 243
      parturients undergoing cesarean section under spinal anesthesia were randomly
      allocated to receive 10, 15, or 25 MUg of intrathecal fentanyl with 10 mg of 0.5%
      hyperbaric bupivacaine. Patients were assessed for clinical efficacy by measuring
      pain score, need for rescue analgesia, conversion to general anesthesia, and
      complaints of inadequacy of surgical anesthesia by the surgeon. The side effects
      assessed were pruritus, nausea, vomiting, dizziness, and decrease in saturation
      and respiratory rate. In addition, neonatal APGAR score, patients' hemodynamics,
      need for vasopressors, onset and duration of sensory, and motor block were
      measured. Results: Patients receiving 25 MUg of fentanyl had a significantly
      higher incidence of pruritus, nausea, and dizziness in addition to a
      significantly prolonged sensory and motor block (P < 0.001). All patients in
      three groups had adequate surgical anesthesia with no statistically significant
      difference in the onset of block, quality of surgical anesthesia, pain scores,
      neonatal APGAR score, hemodynamic variables, and need for vasopressor.
      Conclusion: For patients undergoing cesarean section, 10 or 15 MUg of intrathecal
      fentanyl with 10 mg of bupivacaine provided adequate surgical anesthesia and
      analgesia with minimal side effects.

PMID- 30104834
TI  - Comparative study to assess the quality of analgesia of bupivacaine and
      bupivacaine with dexmedetomidine in ultrasound-guided pectoral nerve block type I
      and II in breast surgeries.
AB  - Background and Aims: Dexmedetomidine has been demonstrated to be safe and
      efficacious in prolonging the duration of peripheral nerve blocks. This study was
      designed to compare the duration, quality of postoperative analgesia, hemodynamic
      stability, and patient's satisfaction with addition of dexmedetomidine to
      bupivacaine versus plain bupivacaine in pectoral nerve block (Pecs) type I and II
      in breast surgeries. Material and Methods: This prospective randomized double
      blind study was carried out in 60 American Society of Anesthesiologists grade I
      III female patients, aged 18-70 years randomly allocated into two equal groups.
      Group A received 10 ml 0.25% bupivacaine for pecs I block and 20 ml 0.25%
      bupivacaine for pecs II block. Group B received 10 ml 0.25% bupivacaine with
      dexmedetomidine for pecs I block and 20 ml 0.25% bupivacaine with dexmedetomidine
      in pecs II block, keeping a total dose of dexmedetomidine of 1 MUg/kg body weight
      and the volume constant in both the groups. Results: Numerical rating scores at
      rest and on abduction of arm were significantly lower in Group B. There was a 40%
      increase in duration of complete analgesia in dexmedetomidine group (1024.0 +/-
      124.9 min) compared to plain bupivacaine (726.4 +/- 155.3 min; P < 0.001). Total
      consumption of injection diclofenac sodium in 24 h was 23% less in Group B (77.5
      +/- 13.6 mg) compared to Group A (100.0 +/- 35.9 mg, P = 0.003). Patient
      satisfaction score was significantly better in dexmedetomidine group. No adverse
      effects were noted in either group. Conclusion: Dexmedetomidine as an adjunct to
      bupivacaine helps prolong the duration and improves the quality of postoperative
      analgesia in pecs I and II block without serious side effects.

PMID- 30104835
TI  - Comparison of pregabalin with gabapentin as preemptive analgesic in lumbar spine
      surgery.
AB  - Background and Aims: Analgesic effect of gabapentin and pregabalin is well
      defined in the treatment of neuropathic pain. Postoperative pain after lumbar
      spine surgery limits the function of patients in the postoperative period, for
      which the search for ideal analgesic goes on. The aim of the present study was to
      compare pregabalin and gabapentin as a pre-emptive analgesic in elective lumbar
      spine surgeries. Material and Methods: In this randomized prospective study, 75
      patients were allocated into three groups of 25 each. Group G, group PG, and
      group P received two capsules of gabapentin 300 mg each, two capsules of
      pregabalin 150 mg each, and two multivitamin capsules, respectively, with sip of
      water 1 hour before the expected time of induction of anesthesia. Time for
      requirement of first dose of rescue analgesia, reduction in postoperative pain
      score and total dose of rescue analgesic used in first 24 hours postoperatively,
      and side effects were compared. Result: Time for requirement of first dose of
      rescue analgesic in PG group was 180.12 min and in G group was 104.16 min, which
      was statistically significant. Both G and PG group had lower visual analogue
      scale (VAS) score in comparison to P group, which was statistically significant.
      Consumption of rescue analgesic was less in G and PG group in comparison to P
      group. Amount of rescue analgesic requirement were low in PG group in comparison
      to G group (P < 0.001). Conclusion: Though both study drugs had produced
      prolonged postoperative analgesia compared to placebo, pregabalin had better
      analgesic profile in postoperative period than gabapentin.

PMID- 30104836
TI  - Pre-emptive caudal epidural analgesia with ropivacaine for lumbosacral spine
      surgery: A randomized case control study.
AB  - Background and Aims: Pre-emptive analgesia using caudal epidural technique is an
      underutilized technique in lumbosacral spine surgery patients. We intend to study
      if pre-emptive analgesia with a single caudal epidural injection of ropivacaine
      is an effective method of postoperative analgesia by assessing the quality and
      duration of pain relief and intraoperative opioid requirement. Material and
      Methods: Eighty patients undergoing lumbosacral spine surgeries by the posterior
      approach were randomized to ropivacaine (R) group (n = 40) and saline (S) group
      (n = 40). Patients in R group received caudal epidural injection of 20 ml of 0.2%
      ropivacaine for surgeries at or below L5 lumbar spine and 25 ml of 0.2%
      ropivacaine for surgeries between L2 and L5 lumbar spine. Patients in S group
      received similar amounts of normal saline. Patients were monitored in the
      immediate postoperative period and at 4, 8, 12, and 24 hours for pain using
      visual analogue scale (VAS) scale. Time to rescue analgesia and intraoperative
      fentanyl requirement were noted. Results: The demographics, duration of
      anesthesia, and hemodynamic variables were comparable in both groups. The mean
      intraoperative fentanyl requirement (P = 0.001) and mean VAS scores were
      significantly lower in the R group in the immediate postoperative period, (P <
      0.001), 4 hours (P < 0.001), 8 hours (P = 0.009), 12 hours (P = 0.007), and 24
      hours (P = 0.046) postoperatively. The mean time to rescue analgesia was
      significantly longer in the R group (P < 0.001) compared to S group. No
      hemodynamic or neurological side-effects were observed in the groups. Conclusion:
      Pre-emptive analgesia with caudal epidural injection of ropivacaine is a safe and
      effective method of postoperative analgesia.

PMID- 30104838
TI  - Head elevation beyond sniffing position - An aid to airway management.

PMID- 30104837
TI  - Ultrasound-guided adductor canal block versus femoral nerve block for
      arthroscopic anterior cruciate ligament repair under general anesthesia.
AB  - Background and Aims: Adductor canal block (ACB) is now an established component
      of multimodal analgesia for knee replacement surgery and is slowly replacing
      femoral nerve block (FNB). It is also gaining popularity for providing pain
      relief in knee arthroscopies including anterior cruciate ligament reconstruction
      surgery (ACLR). Data is lacking from the Indian subcontinent on comparing ACB to
      the traditional FNB for ACLR. Hence, we conducted the present study to compare
      ACB and FNB in ACLR under general anesthesia. Material and Methods: Sixty
      patients were randomized to receive either ACB or FNB under ultrasound guidance.
      Postoperatively, quadriceps muscle strength (straight leg raise and time up and
      go; TUG test) and quality of analgesia (numeric rating scale; NRS and patient
      satisfaction score) were assessed every 6 hour, and thereafter, up to 48 hours.
      The time of rescue analgesia and total analgesic consumption (tramadol) were also
      recorded. Data was statistically analyzed and P < 0.05 was considered to be
      significant. Results: Patients receiving ACB had significantly less quadriceps
      weakness (P < 0.001) compared to FNB on postoperative day (POD) 1. In addition,
      patient satisfaction score was statistically higher (P < 0.05) in FNB on POD1.
      Both the above parameters were comparable on POD2. No statistically significant
      difference was recorded in NRS, time for rescue analgesia, and total analgesic
      consumption among the two groups. Conclusion: ACB preserves quadriceps motor
      strength while providing analgesia comparable to FNB in patients undergoing ACLR.
      However, patient satisfaction score is better with FNB than ACB.

PMID- 30104839
TI  - Functional barriers to acceptance of the WHO Surgical Safety Checklist are just
      myths!

PMID- 30104840
TI  - Anesthetic challenges and successful management of a child with Pelizaeus
      Merzbacher disease using general and caudal anesthesia.

PMID- 30104841
TI  - Comparison of two different techniques of serratus anterior plane block: A
      clinical experience.

PMID- 30104842
TI  - Prediction of outcome in perforation peritonitis: Sequential organ function
      assessment score and inflammatory mediators.

PMID- 30104843
TI  - Peripherally acting opioid receptor antagonists in pediatric patients.

PMID- 30104844
TI  - Intra-operative emergency airway management in a child with broken tracheal limb
      of Montgomery T-tube.

PMID- 30104845
TI  - Inappropriately sized connector: An ingredient for catastrophe!?

PMID- 30104846
TI  - Nasal assessment for nasotracheal intubation: A ray of hope.

PMID- 30104847
TI  - Refractory ICP with Mycotic Aneurysm - 23.4% Saline or Mannitol?

PMID- 30104848
TI  - Congenital adrenal hyperplasia due to 17-alpha hydroxylase deficiency with
      hypertensive encephalopathy, hypoglycemic seizures and adrenal insufficiency.

PMID- 30104849
TI  - Anesthetic management of laparoscopic splenectomy in a case of Evans Syndrome
      with systemic lupus erythematosis.

PMID- 30104850
TI  - Psoas compartment block for intraoperative anesthesia for fracture neck of femur:
      Case report.

PMID- 30104851
TI  - Anticoagulant-induced subdural hemorrhage in a patient with Guillain-Barre
      syndrome: An anesthetic challenge.

PMID- 30104852
TI  - Vasovagal mediated cardiac arrest during epidural catheter insertion in a patient
      with previous uneventful surgeries under regional anesthesia.

PMID- 30104853
TI  - Anesthetic management of a patient with MELAS.

PMID- 30104854
TI  - Intraoperative baroreflex failure following lignocaine infiltration during
      unilateral radical neck dissection.

PMID- 30104855
TI  - Diaphragmatic hernia after cesarean section masquerading as hydropneumothorax.

PMID- 30104856
TI  - Initial management in blunt trauma neck.

PMID- 30104857
TI  - Alternate technique of exchanging nasotracheal tube in a case of
      temporomandibular joint ankylosis.

PMID- 30104858
TI  - Anesthetic management of a case of neurodegeneration brain iron accumulation
      (Hallervorden-Spatz disease).

PMID- 30104859
TI  - Rupture of renal angiomyolipoma during pregnancy: A case report.

PMID- 30104860
TI  - Ultrasonography can unfold many Mysteries!

PMID- 30104861
TI  - Tear meniscus evaluation after microkeratome laser in situ keratomileusis,
      femtosecond laser and femtosmile laser techniques using anterior segment optical
      coherence tomography.
AB  - Purpose: The purpose of this study was to compare the effects of three different
      corneal refractive surgeries: microkeratome laser in situ keratomileusis (LASIK),
      femtosecond laser in situ keratomileusis (FS-LASIK) and femtosecond small
      incision lenticule extraction (FS-SMILE) on 6-month postoperative stability of
      tear film to provide a basis for selection of operative procedures. Patients and
      methods: This is a prospective, randomized, comparative study that included 90
      eyes of three equal groups of patients. Each group was subjected to a different
      laser technique: LASIK, FS-LASIK and FS-SMILE. Using anterior segment spectral
      domain optical coherence tomography (AS-SD-OCT), the lower tear meniscus
      parameters were measured preoperatively and 1 week, 1 month, 3 months and 6
      months postoperatively. Changes were studied and compared. Results: There was a
      statistically significant difference in tear meniscus height (TMH) between FS
      SMILE and FS-LASIK in the first week (P = 0.003) and first month (P = 0.002) with
      no statistically significant difference between both techniques at 3 and 6 months
      postoperatively. In FS-SMILE, TMH returned to 95% of its preoperative level after
      1 month. There was no statistically significant difference in TMH between FS
      LASIK and microkeratome LASIK techniques after 1 week and 1 month, but there was
      a statistically significant difference between both techniques in 3 months (P =
      0.019) and 6 months (P = 0.032). Tear meniscus area (TMA) showed no statistically
      significant difference between FS-SMILE and FS-LASIK at all points of follow-up,
      but there was a statistically significant difference between both techniques and
      microkeratome LASIK (all P < 0.05). Microkeratome LASIK parameters failed to
      reach the preoperative level till 6 months. Conclusion: Early recovery of the
      lower TMH can be achieved as early as 1 month post-operatively with the FS-SMILE
      technique compared to FS-LASIK and microkeratome LASIK techniques.

PMID- 30104862
TI  - Finasteride nano-transferosomal gel formula for management of androgenetic
      alopecia: ex vivo investigational approach.
AB  - Introduction: Finasteride (FIN) is known as type II 5alpha-reductase inhibitor,
      which has been approved for the treatment and prevention of androgenetic
      alopecia. Administration of FIN by oral route has led to undesirable systemic
      side effects that include mood disturbance, gynecomastia, decreased libido,
      erectile dysfunction, and ejaculation disorder. The aim was to improve FIN
      delivery through skin layers and hair follicles that could possibly reduce its
      major side effects resulting from long-term oral administration for the treatment
      and prevention of male pattern baldness. Materials and methods: FIN was
      formulated as nano-transferosomal (NTF) gel formulations (F1-3). The prepared
      formulations were characterized for encapsulation efficiency, particle size, ex
      vivo skin permeation, and kinetic modeling. In addition, visualization of NTF
      skin penetration using a fluorescence laser microscope was carried out for the
      selected formula (F2). Results and discussion: The results showed that FIN
      encapsulation efficiency percentage was 69.72 +/- 8.36, 89.43 +/- 6.82, and 93.1
      +/- 1.93 for F1, F2, and F3, respectively. FIN-NTF average vesicle sizes were
      299.6 +/- 45.6, 171 +/- 25.6, and 197.4 +/- 29.1 nm for F1, F2, and F3,
      respectively. FIN-NTF formulations (F1-3) showed enhancement and improvement in
      the amount of FIN permeated compared with raw FIN gel formula. The NTF formula
      revealed uniform fluorescence (rhodamine) intensity across rat skin, which
      indicated improved delivery through skin layers compared with control gel
      formula. Conclusion: These results indicated that NTF gel formula showed the
      ability to boost FIN delivery across skin layers and could be applied as an
      alternative for oral therapy.

PMID- 30104863
TI  - Discovery of nonnucleoside inhibitors of polymerase from infectious pancreatic
      necrosis virus (IPNV).
AB  - Introduction: Infectious pancreatic necrosis virus (IPNV) causes serious losses
      in several fish species of commercial interest. IPNV is a non-enveloped double
      stranded RNA virus with a genome consisting of two segments A and B. Segment B
      codes for the VP1 protein, a non-canonical RNA-dependent RNA polymerase that can
      be found both in its free form and linked to the end of genomic RNA, an essential
      enzyme for IPNV replication. Materials and methods: We take advantage of the
      knowledge over the allosteric binding site described on the surface of the thumb
      domain of Hepatitis C virus (HCV) polymerase to design new non-nucleoside
      inhibitors against the IPNV VP1 polymerase. Results: Molecular docking techniques
      have been used to screen a chemical library of 23,760 compounds over a defined
      cavity in the surface of the thumb domain. Additional ADMET (absorption,
      distribution, metabolism, excretion, and toxicity) filter criteria has been
      applied. Conclusion: We select two sets of 9 and 50 inhibitor candidates against
      the polymerases of HCV and IPNV, respectively. Two non-toxic compounds have been
      tested in vitro with antiviral capacity against IPNV Sp and LWVRT60 strains in
      the low uM range with different activity depending on the IPNV strain used.

PMID- 30104865
TI  - Consumer opinions on adverse events associated with medicines and vaccines.
AB  - Introduction: Despite the availability of an Australian consumer adverse event
      (AE) reporting system for over 50 years, reporting rates remain low. A
      comprehensive understanding of consumer perceptions and experiences regarding AEs
      is needed to further ascertain factors impacting their engagement in AE
      reporting. Aim: The aim of this study was to explore consumer opinions about AEs
      potentially associated with medicines and vaccines, and their experiences and
      understanding of managing and reporting AEs. Methods: Six focus groups were
      conducted across metropolitan Sydney with a total of 48 adult participants. A
      semi-structured focus group topic guide was developed to explore consumers'
      understanding, experiences, and actions taken in relation to AEs; and
      perspectives on managing treatment benefits and harms. Discussions were audio
      recorded with participant permission and transcribed verbatim. Transcripts were
      thematically analyzed. Results: Consumers acknowledged the potential for side
      effects (SEs), however inaccurately estimated SE risk in response to verbal
      descriptors such as "common." Consumer appraisal of treatment benefits and harms
      was influenced by factors such as medical condition(s), previous experiences, and
      beliefs. Although many had experienced SEs, consumers only reported them if
      considered severe or troublesome. Minimal awareness of consumer AE reporting
      systems was evident. Doctors were the primary avenue for reporting; consumers
      preferred doctors to act as the intermediary in reporting AEs to an independent
      body. Conclusion: Consumers' lack of awareness of AE reporting systems was
      evident. With the complexities inherent in benefit/harm risk appraisal,
      information seeking, and AE reporting preferences, better consumer understanding
      of AEs and the systems available for reporting is needed.

PMID- 30104864
TI  - Factors affecting patient satisfaction with ecdemic medical care: a cross
      sectional study in Nanchang, China.
AB  - Purpose: This study aimed to determine the factors that influence patient
      satisfaction with ecdemic medical care. Materials and methods: Eight hundred and
      forty-four face-to-face interviews were conducted between October and November
      2017 in two high-profile hospitals in Nanchang, China. Patient satisfaction was
      divided into lowest and highest satisfaction groups according the 80/20 rule.
      Demographic factors associated with patient satisfaction were identified by
      logistic regression models. Results: Respondents' main reasons for choosing a non
      local hospital were "high level of medical treatment" (581/844), "good reputation
      of the hospital" (533/844), and "advanced medical equipment" (417/844). The top
      three items that dissatisfied the ecdemic patients were "long time to wait for
      treatment" (553/844), "complicated formalities" (307/844), and "poor overall
      service attitude" (288/844). Fewer female patients (adjusted odds ratio [AOR]
      =1.47, 95% confidence interval [CI] =1.03-2.11), patients with a family per
      capita monthly income (FPMI) between 3,001 and 5,000 CNY (AOR =1.40, 95% CI =1.01
      2.17), inpatients (AOR =1.46, 95% CI =1.01-2.13), and more patients with an FPMI
      >7,000 CNY (AOR =0.43, 95% CI =0.20-0.92) were detected in the lowest
      satisfaction group. Fewer patients with an associate's or bachelor's degree (AOR
      =2.40, 95% CI =1.37-4.20) and patients with an FPMI >7,000 CNY (AOR =3.02, 95% CI
      =1.10-8.33) were detected in the highest satisfaction group. Moreover, more
      inpatients (AOR =0.70, 95% CI =0.54-0.97) and those aged 46-65 years (AOR =0.63,
      95% CI =0.33-0.98) were detected in the highest satisfaction group. Conclusion:
      Findings suggested that managers of the medical facilities should note the
      importance of increasing their publicity through a rapidly developing media, as
      well as the necessity of creating a more patient-friendly medical care
      experience. Hospitals should also focus on the medical care experience of
      patients with relatively lower and higher income levels, male ecdemic patients,
      and ecdemic outpatients.

PMID- 30104866
TI  - A pathogenic PSEN2 p.His169Asn mutation associated with early-onset Alzheimer's
      disease.
AB  - Background: Autosomal dominant early-onset Alzheimer's disease (EOAD) is
      genetically heterogeneous and has been associated with mutations in 3 different
      genes, coding for amyloid precursor protein (APP), presenilin 1 (PSEN1), and
      presenilin 2 (PSEN2). Most frequent cases are associated with mutations in the
      PSEN1 gene, whereas mutations in the APP and PSEN2 genes are rare. Methods:
      Patient who presented progressive memory decline in her 50s was enrolled in this
      study. A broad battery of neuropsychological tests and neuroimaging was applied
      to make the diagnosis. Genetic tests were performed in the patient to evaluate
      possible mutations using next-generation sequencing (NGS). The pathogenic nature
      of missense mutation and its 3D protein structure prediction were performed by in
      silico prediction programs. Results: A pathogenic mutation in the PSEN2 gene in a
      Korean patient associated with EOAD was identified. Targeted Next-generation
      sequencing and Sanger sequencing revealed a heterozygous C to A transition at
      position 505 (c.505C>A), resulting in a probably missense mutation at codon 169
      (p.His169Asn) in PSEN2. PolyPhen-2 and SIFT software analyses predicted this
      mutation to be a probable damaging variant. This hypothesis was supported by the
      results of 3D in silico modelling analyses that predicted the p.His169Asn may
      result in major helix torsion due to histidine to asparagine substitution.
      Mutation may cause additional stresses with hydrophobic residues on the surface
      that interact inside the transmembrane domain III, which is a conserved domain in
      PSEN2 His169. Conclusion: These findings revealed that the p.His169Asn might be
      an important residue in PSEN2, which may alter the functions of PSEN2, suggesting
      its potential involvement with AD phenotype. Future functional studies are needed
      to evaluate the role of PSEN2 p.His169Asn mutation in AD disease progression.

PMID- 30104867
TI  - Comparison of the acute effects of traditional versus high velocity resistance
      training on metabolic, cardiovascular, and psychophysiological responses in
      elderly hypertensive women.
AB  - Objectives: The aim of the present study was to compare the acute effects of
      traditional resistance training (RT) versus high velocity RT (HVRT) on metabolic,
      cardiovascular, and psychophysiological responses in elderly hypertensive women.
      Methods: Fifteen elderly women (mean age +/- standard deviation, 67.1+/-6.9
      years) classified as having hypertension stage 1 or 2 were randomly allocated to
      complete traditional RT or HVRT; 1 week later, subjects allocated to RT completed
      the HVRT session and vice-versa. Heart rate, blood pressure, affective response,
      perceived effort, and blood samples analyzing lactate, nitrate, nitrite,
      oxidative damage (thiobarbituric acid reactive substances [TBARS]), and 6-hydroxy
      2,5,7,8-tetramethylchroman-2-carboxylic acid equivalent antioxidant capacity
      (TEAC) collected before and after training sessions were assessed. Nutritional
      counseling was provided regarding nutrients that could affect cardiovascular and
      nitrate/nitrite analysis. Results: Systolic blood pressure was not statistically
      different (p>0.05) between conditions at the beginning and during 30 minutes
      after sessions. Diastolic blood pressure, rate pressure product, and heart rate
      were not statistically different (p>0.05) between conditions at the beginning and
      during 45 minutes after sessions. Nitric oxide was significantly higher
      (p<0.0005) for HVRT compared to RT after 30 minutes of exercise. TBARS and TEAC
      were significantly higher (p<0.05) for HVRT compared with RT only immediately
      after exercise. There were no differences for psychophysiological variables
      between protocols. Conclusion: The acute cardiovascular and metabolic responses,
      including oxidative stress, are transient and within normal values. Taken
      together with the positive affective responses, both HVRT and RT with this
      intensity and volume seem to be safe for elderly hypertensive women under
      medication.

PMID- 30104868
TI  - Stay active for life: physical activity across life stages.
AB  - Purpose: This paper concerns participation of Poles aged 15+ years in leisure
      time and transport-related physical activity (PA) with a special focus on the
      life stages. The purpose of the paper was to analyze types of exercises, current
      and future behavior concerning PA, availability of sport and recreation
      facilities, and factors having the strongest relation with undertaking PA at a
      sufficient level according to pro-health recommendations of World Health
      Organization (WHO). Patients and methods: A survey was carried out on the
      representative sample (n=2,000). Respondents were classified in accordance to
      their life stages with a two-step cluster analysis. Relationships between meeting
      the dose of PA required for health recommendations and a membership in groups of
      life stages were evaluated using log-linear analysis. The strength of this
      relationship was expressed by the odds ratio. In order to capture relationships
      between meeting WHO recommendations and a set of explanatory variables, a
      predictive model was built. Results: Life stages and various related events have
      a significant relation with a decrease of PA. Among groups of a particular risk,
      there are professionally active and unemployed people aged 50-64 years without
      children as well as retirees aged 65+ years who do not meet WHO recommendations
      (45.3; 50.4% and 47.6%). The unemployed and retirees more frequently (p<0.0001)
      do not or cannot practice sport and do not think that a change of their situation
      is expected soon. However, 35% of professionally active people aged 50-64 years
      without children and 18.2% of unemployed people declare that they are currently
      not active but if they had the possibility, they would start practicing sport.
      Conclusion: Campaigns promoting PA should be targeted at groups of a particular
      risk. Any attempts of increasing PA or changing tendencies of its decrease should
      consider life conditions of these persons, as well as their needs, motivations,
      and barriers.

PMID- 30104869
TI  - Symptom-related sputum microbiota in stable chronic obstructive pulmonary
      disease.
AB  - Background: The role of airway microbiota in COPD is highly debated. Symptomology
      assessment is vital for the management of clinically stable COPD patients;
      however, the link between symp toms and the airway microbiome is currently
      unknown. Purpose: The present study aimed to evaluate the relationship among
      stable COPD patients. Patients and methods: We conducted pyrosequencing of
      bacterial 16S rRNA using induced sputum samples in a Han Chinese cohort that
      included 40 clinically stable COPD patients and 19 healthy controls. Results:
      Alterations in community composition and core bacte rial taxa (Neisseria
      subflava, etc.) were observed in patients with severe symptoms compared with
      controls. The co-occurrence network indicated that the key microbiota enriched in
      COPD patients showed higher expression in patients with severe symptoms. The
      association pattern of symptoms with the sputum microbiome was obviously
      different from that of lung function in COPD patients. Conclusion: These findings
      broaden our insights into the relationship between the sputum microbiota and the
      symptom severity in COPD patients, emphasizing the role of symptoms in the airway
      microbiome, independent of lung function.

PMID- 30104870
TI  - COPD affects worker productivity and health care costs.
AB  - Purpose: This study aimed to measure the true burden of COPD by calculating
      incremental direct and indirect costs. Direct medical resource use, productivity
      metrics, and COPD-specific resource use and costs were also evaluated. Patients
      and methods: This was a retrospective, observational, matched cohort study using
      administrative claims data from the Truven Health MarketScan(r) Commercial Claims
      and Encounters and the Health and Productivity Management databases (2007-2010).
      Working-age (18-65 years) patients with COPD were identified as having at least
      one hospitalization or one emergency department visit or two outpatient visits.
      Patients in the non-COPD cohort did not have a diagnosis of COPD during the study
      period. Outcomes were evaluated in the first full calendar year after the year of
      identification (index). Results: Of the 5,701 patients with COPD identified, 3.6%
      patients were frequent exacerbators (>=2), 10.4% patients were infrequent
      exacerbators (1), and 86% patients were non-exacerbators (0). When compared with
      the 17,103 patients without COPD, the incremental direct cost of COPD was
      estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623;
      P<0.001). Loss in productivity was significantly greater in patients with COPD,
      with an average of 5 more days/year of absence from work and incremental indirect
      costs from short-term disability of $641 (P<0.001). Direct costs for frequent
      exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were
      significantly higher than those for non-exacerbators ($11,395, P<0.001).
      Conclusion: Working-age patients with COPD incur statistically significantly
      higher direct and indirect costs and use more resources compared with those who
      do not have COPD.

PMID- 30104871
TI  - Morphometric analysis of mitochondria in lymphocytes of patients with
      exacerbations of chronic obstructive pulmonary disease - pilot study.
AB  - Introduction: Exacerbations of chronic obstructive pulmonary disease (ECOPD) are
      important events in the course of the disease, negatively influencing health
      status and disease progression. Therefore, there is a strong need for deeper
      understanding of the pathology of ECOPD to elaborate new therapeutic approaches
      and ameliorate prognoses. Contributions of mitochondria to pathobiology of COPD
      are still under investigation, although growing evidence suggests their important
      role in this disease. The aim of our study was to assess the morphometric
      parameters of mitochondria in lymphocytes of patients with ECOPD. Patients and
      methods: Lymphocytes were isolated from the peripheral blood of patients with
      COPD. Transmission electron microscopy was used to assess absolute number of
      mitochondria per cell, mitochondrial content, and morphometric parameters of
      individual mitochondria. We also counted indexes for elongation and
      interconnectivity. Results: Eighteen patients (9 with ECOPD and 9 in the stable
      period of the disease) were analyzed. We observed significantly lower length of
      mitochondrion (P=0.03) and significant decrease both in elongation (P=0.03) and
      interconnectivity indexes (P=0.04) in ECOPD patients. Conclusions: The
      morphometric parameters of mitochondria in lymphocytes derived from patients
      during the early period of ECOPD requiring hospitalization are altered in
      comparison to patients in the stable period of the disease. This suggests their
      contribution to pathobiology of ECOPD. These preliminary outcomes should be
      further validated in larger size samples.

PMID- 30104872
TI  - Management of severe COPD exacerbations: focus on beclomethasone
      dipropionate/formoterol/glycopyrronium bromide.
AB  - The major determinant of the decline in lung function, quality of life, and the
      increased mortality risk in patients with COPD is represented by severe acute
      exacerbations of the disease, that is, those requiring patients' hospitalization,
      constituting a substantial social and health care burden in terms of morbidity
      and medical resource utilization. Different long-term therapeutic strategies have
      been proposed so far in order to prevent and/or reduce the clinical and social
      impact of these events, the majority of which were extrapolated from trials
      initially focused on the effect of long-acting muscarinic antagonist and
      subsequently on the efficacy of long-acting beta2-agonists in combination or not
      with inhaled corticosteroids. The option to employ all three classes of molecules
      combined, despite the limited amount of evidence in our possession, represents a
      choice currently proposed by international guidelines; however, current
      recommendations are often based mainly on observational studies or on the results
      of secondary outcomes in randomized controlled trials. The present narrative
      review evaluates the available trials that investigated the efficacy of inhaled
      therapy to prevent COPD exacerbations and especially severe ones, with a
      particular focus on beclomethasone dipropionate/formoterol/glycopyrronium bromide
      fixed dose combination, which is the first treatment that comprises all the three
      drug classes, specifically tested for the prevention of moderate and severe COPD
      exacerbations.

PMID- 30104873
TI  - Impact of bronchiectasis on the frequency and severity of respiratory
      exacerbations in COPD.

PMID- 30104874
TI  - The effect of the carbodiimide cross-linker on the structural and
      biocompatibility properties of collagen-chondroitin sulfate electrospun mat.
AB  - Background: Collagen and chondroitin sulfate (CS) are an essential component of
      the natural extracellular matrix (ECM) of most tissues. They provide the
      mechanical stability to cone the compressive forces in ECM. In tissue
      engineering, electrospun nanofibrous scaffolds prepared by electrospinning
      technique have emerged as a suitable candidate to imitate natural ECM functions.
      Cross-linking with 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide
      hydrochloride/N-hydroxy succinimide can overcome the weak mechanical integrity of
      the engineered scaffolds in addition to the increased degradation stability under
      physiological conditions. Materials and methods: This study has synthesized
      nanofibrous collagen-CS scaffolds by using the electrospinning method. Results:
      The results have shown that incorporation of CS in higher concentration, along
      with 1-ethyl-3-(3-dimethyl-aminopropyl)-1-carbodiimide hydrochloride/N-hydroxy
      succinimide, enhanced mechanical stability. Scaffolds showed more resistance to
      collagenase digestion. Fabricated scaffolds showed biocompatibility in corneal
      epithelial cell attachment. Conclusion: These results demonstrate that cross
      linked electrospun CO-CS mats exhibited a uniform nanofibrous and porous
      structure, especially for lower concentration of the cross-linker and may be
      utilized as an alternative effective substrate in tissue engineering.

PMID- 30104875
TI  - Iridium (III) complex-loaded liposomes as a drug delivery system for lung cancer
      through mitochondrial dysfunction.
AB  - Background and aim: Iridium (Ir)-based complex is a potential antitumor
      ingredient, but its poor physicochemical properties such as hydrophobicity and
      low biocompatibility hamper further application. Liposome provides a potential
      delivery approach for improving the poor physicochemical property and reducing
      the side effects of antitumor drug. In this study, we aimed at incorporating Ir
      ([Ir(ppy)2(BTCP)]PF6) into liposomes to enhance the biocompatibility and
      sustained release of Ir for intravenous administration and to elucidate the
      mechanism in A549 cells. Materials and methods: Ir-loaded PEGylated liposomes
      (Lipo-Ir) were formulated by thin-film dispersion and ultrasonic method.
      Morphology, size distribution, and zeta potential of Lipo-Ir were examined by
      transmission electron microscopy (TEM) and Zetasizer. The released profile and
      biocompatibility were investigated by dialysis method and hemolysis test,
      respectively. Additionally, the cytotoxic activity and mechanism of Lipo-Ir and
      Ir inducing apoptosis in A549 cells were evaluated. Results: Lipo-Ir can keep
      sustained release, excellent biocompatibility, and physical stability. The
      average particle size, polydispersity index, zeta potential, encapsulation
      efficiency, and drug loading are 112.57+/-1.15 nm, 0.19+/-0.02, -10.66+/-0.61 mV,
      94.71%+/-3.21%, and 4.71%+/-0.41%, respectively. 3-(4,5-dimethylthiazole)-2,5
      diphenltetraazolium bromide (MTT) assay show that Lipo-Ir and Ir display high
      cytotoxicity against selected cancer cells. Furthermore, the apoptotic features
      of morphology, depolarization of mitochondrial membrane potential, increase in
      the reactive oxygen species (ROS) levels, and disorder of Ca2+ homeostasis are
      observed after treating A549 cells with Ir and Lipo-Ir. Besides, Lipo-Ir can
      arrest the cell growth in G0/G1 phase. Conclusion: The studies demonstrate that
      Lipo-Ir can trigger apoptosis in A549 cells via ROS-mediated mitochondrial
      dysfunctions, and the biocompatible and sustained Lipo-Ir will be a promising
      drug delivery system.

PMID- 30104876
TI  - Cytological and cytometric analysis of oral mucosa in patients with Alzheimer's
      and Parkinson's disease.
AB  - Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are the two
      most common neurodegenerative diseases. Recent studies have sought to identify
      precursor symptoms of AD and PD that occur before the onset of the disease. We
      evaluated changes in the oral mucosa of patients with AD and PD using a
      stereological method. Patients and methods: The study included 29 patients with
      AD, 30 patients with idiopathic PD, and 30 healthy volunteers. Brush biopsies
      were obtained from all participants, and the nucleator method was used to
      estimate the volume of cells obtained from the buccal mucosa. Results:
      Cytomorphometric analysis revealed that the nuclear volume was 484.39+/-117.10
      um3 in the AD group, 509.71+/-132.26 um3 in PD patients, and 509.30+/-100.21 um3
      in the control group. The cytoplasmic volume was 115,456.60+/-30,664.98 um3 in
      the AD group, 103,097.93+/-25,034.65 um3 in PD patients, and 109,528.45+/
      28,381.43 um3 in the control group. The nuclear and cytoplasmic volumes were not
      significantly different among groups (P>0.05). Conclusion: The cytomorphometric
      analysis revealed no significant differences in the cytoplasmic and nuclear
      volumes of buccal cells obtained from patients with AD and PD and healthy
      volunteers.

PMID- 30104877
TI  - Cognitive and metacognitive factors among alcohol-dependent patients during a
      residential rehabilitation program: a pilot study.
AB  - Purpose: The aims of this pilot study were to examine cognitive factors (brooding
      and craving) together with positive/negative metacognitive beliefs about alcohol
      during a residential program for alcohol addiction and to explore relationships
      with psychological variables at discharge, with the scope of identifying
      predictive factors of psychological outcome and patients at greatest risk of
      relapse. Methods: Thirty patients underwent a brief semistructured interview on
      admission to a 28-day rehabilitation program for alcohol addiction, and completed
      at admission and discharge the following five self-report questionnaires: 1)
      brooding (Brooding subscale of Ruminative Response Scale [B-RRS]), 2) craving
      (Penn Alcohol Craving Scale [PACS]), 3) positive beliefs about alcohol use
      (Positive Alcohol Metacognitions Scale [PAMS]), 4) negative beliefs about alcohol
      use (Negative Alcohol Metacognitions Scale [NAMS]), and 5) the psychophysical
      state of health (Cognitive Behavioral Assessment - Outcome Evaluation [CBA-OE]).
      Results: Significant changes were found between admission and discharge in CBA
      OE, B-RRS, and PACS. Brooding at admission was a significant predictor of post
      treatment psychological variables of "anxiety", "depression", and "psychological
      distress", whereas craving at admission was a good predictor of "perception of
      positive change" at discharge. Conclusion: Our results confirm the importance of
      brooding in mood regulation and its role in the development and maintenance of
      problem drinking. In addition, craving was negatively associated with the
      perception of positive change in the post-treatment outcomes and was a predictor
      of this psychological variable, which includes features related to the
      individual's resilience and strength. The changes in metacognitive beliefs
      regarding alcohol use were not statistically significant, but we found a
      reduction in positive metacognitions and an increase in negative alcohol-related
      beliefs; future studies are needed to further explore this issue.

PMID- 30104878
TI  - Prognostic role of Toll-like receptors in cancer: a meta-analysis.
AB  - Background: Recent studies have shown that Toll-like receptors (TLRs) may be
      associated with cancers. The aim of this meta-analysis is to summarize the
      predicting role of TLRs for survival in patients with a variety of carcinomas.
      Materials and methods: Eligible studies were identified and assessed for quality
      through multiple search strategies. We collected data from studies investigating
      the relationship between the expression level of TLRs and survival in cancer
      patients. Studies were pooled and combined hazard ratios (HRs) of TLRs for
      survival were analyzed. Results: A total of 24 studies, including 2,812 patients
      with various cancers, were identified for the meta-analysis. Importantly, this
      meta-analysis showed that higher expression levels of TLR4 or TLR7 in tumor
      tissues could predict poorer survival, with the pooled HR being 1.29 (95% CI:
      1.17, 1.42) and 1.71 (95% CI: 1.38, 2.12), respectively. However, higher
      expression of TLR9 had no significant association with outcome as HR was 0.84
      (95% CI: 0.62, 1.115). Heterogeneity existed in TLR4 and TLR9 studies (P-value
      <0.001) but not in TLR7 studies (P-value >0.05). Conclusion: The expression level
      of TLR4 or TLR7 in cancerous tissue may have a prognosis value in patients with
      various cancers.

PMID- 30104879
TI  - Assessment of the Berlin Questionnaire for evaluation of hypoxemia risk in
      subjects undergoing deep sedation for screening gastrointestinal endoscopy.
AB  - Background: Subjects with obstructive sleep apnea (OSA) are vulnerable to
      sedation-related complications during endoscopic procedures. A significant
      portion of subjects undergoing routine endoscopy is at high risk of OSA, but most
      are undiagnosed. The purpose of this study was to estimate the prevalence of high
      risk for OSA among Chinese subjects undergoing deep sedation for screening
      gastrointestinal endoscopy and to evaluate the hypoxemia risk of these examinees
      stratified by Berlin Questionnaire (BQ). Patients and methods: We performed a
      prospective cohort study in subjects undergoing deep sedation with monitored
      anesthesia care for combined esophagogastroduodenoscopy plus colonoscopy.
      Subjects who were Chinese were stratified into high- and low-risk groups for OSA
      by administration of BQ. Deep sedation was achieved via a propofol target
      controlled infusion system. Hypoxemia was defined as pulse oximetry reading of
      less than 90%. The frequency of hypoxemia was compared between high- and low-risk
      groups for OSA. Results: A total of 615 Chinese subjects were recruited during
      the study period, and 614 subjects were included for analysis. Two hundred
      eighteen (35.5%) subjected were classified to be at high risk of OSA, and 396
      (64.5%) were stratified to be at low risk of OSA by BQ. Hypoxemia occurred in 83
      (13.5%) subjects during endoscopy procedures. The risk of developing hypoxemia in
      the high-risk group was significantly higher when compared to that of the low
      risk group subjects (24.8% vs 7.3%; relative risk, 3.37; 95% CI, 2.22-5.13).
      Conclusion: About one-third Chinese subjects undergoing deep sedation for
      screening endoscopy were at high risk of OSA. Subjects at high risk of OSA are
      associated with an increased risk of hypoxemia in comparison to the low-risk
      group when undergoing deep sedation for screening gastrointestinal endoscopy.

PMID- 30104880
TI  - Management and outcomes of hyperparathyroidism: a case series from a single
      institution over two decades.
AB  - Background: Hyperparathyroidism is a frequent endocrine disorder with variable
      clinical manifestations and outcomes. We aimed to evaluate clinical
      presentations, management and outcomes of hyperparathyroidism. Methods: A
      retrospective study was conducted to include all patients presented with
      hyperparathyroidism between 1995 and 2014 at a single tertiary hospital with an
      average follow-up period of 46 months. Data were reviewed for clinical
      presentations, diagnostic work-up, intraoperative findings, management, and
      outcomes. Result: We identified 161 patients with hyperparathyroidism; 69% were
      females and the mean age was 49.4+/-15 years. Patients presented mainly with
      musculoskeletal (65.8%), renal (37.3%), gastrointestinal tract (53.8%) and
      neuropsychiatric (8.8%) manifestations. At presentation, mean serum calcium and
      parathyroid hormone levels were elevated while mean vitamin D level was lower.
      Sestamibi-99mTc (MIBI) scintigraphy was done for 134 patients (83.2%) and was
      positive in 94 (70%). Primary hyperparathyroidism (67.7%) was the most frequent
      diagnosis followed by secondary (29.8%) and tertiary hyperparathyroidism (2.5%).
      The frequent indication for surgery was hypercalcemia (67.3%), bone disease
      (35.6%) and renal calculi (28.9%). The main postoperative pathology was
      parathyroid adenoma (63.1%) followed by hyperplasia (37.3%). Fourteen (8.9%) and
      18 (11.4%) patients had persistent and recurrent hyperparathyroidism,
      respectively. Autotransplantation of parathyroid tissue was done in 36 cases.
      Conclusion: Primary hyperparathyroidism is the most frequent cause of the
      parathyroid disease. Parathyroidectomy is the effective surgical approach in
      symptomatic patients. Further studies are needed to establish the association
      between vitamin D levels, renal disorders and persistent or recurrent
      hyperparathyroidism.

PMID- 30104881
TI  - Anxiety and depression predicted quality of life among patients with heart
      failure.
AB  - Purpose: Anxiety and depression are prevalent among patients with heart failure.
      However, their effect on the quality of life (QoL) is not well investigated in
      developing countries. Therefore, the purpose of this study was to test the effect
      of anxiety and depression on QoL among Jordanian patients with heart failure.
      Patients and methods: Two hundred patients with a confirmed diagnosis of heart
      failure from 1 governmental and 1 private hospital in Amman, Jordan, were
      recruited between March and August, 2017. A descriptive, cross-sectional design
      was used. Anxiety and depression were measured using the Arabic version of the
      Hospital Anxiety and Depression Scale. QoL was measured using the Arabic version
      of the Short Form-36. Results: Patients reported poor QoL in both physical
      component summary (M +/- SD; 35.8+/-9.6) and mental component summary (M +/- SD;
      41.5+/-11.3). Prevalence rates for anxiety and depression were 62% and 65%,
      respectively. In stepwise regression analysis, anxiety and depression were
      independent predictors for poor QoL in both summaries, p<0.001. Conclusion:
      Patients with heart failure have poor QoL and high anxiety and high depression
      prevalence rates. Inclusion of routine assessment and management of anxiety and
      depression in heart failure protocols is highly recommended.

PMID- 30104882
TI  - Reversible posterior leukoencephalopathy syndrome induced by apatinib: a case
      report and literature review.
AB  - Reversible posterior leukoencephalopathy syndrome (RPLS) is a rare clinical
      radiologic syndrome. There are reports that RPLS may be associated with cancer
      therapy including some chemotherapy drugs and antiangiogenic drugs. This paper
      reported a case of RPLS induced by apatinib, a vascular endothelial growth factor
      receptor 2 (VEGFR-2) tyrosine kinase inhibitor. A 47-year-old cervical cancer
      patient was administered apatinib, and 3 months later, headache, dizziness,
      blurred vision, and hypertension appeared. She was diagnosed with RPLS by nuclear
      magnetic resonance imaging (MRI). After apatinib discontinuation and normotensive
      treatment, her symptoms completely reversed. Antiangiogenic drugs potentially
      damage the balance of the blood-brain barrier by directly injuring vascular
      endothelial cells, resulting in the occurrence of RPLS. This case is the first
      report of RPLS induced by apatinib.

PMID- 30104883
TI  - Combination chemotherapy with Zyflamend reduced the acquired resistance of
      bladder cancer cells to cisplatin through inhibiting NFkappaB signaling pathway.
AB  - Background: Cisplatin-based chemotherapy is mainstay treatment in urinary bladder
      cancer (UBC). However, tumor recurrence frequently occurs with the acquisition of
      cisplatin resistance. We explored the potential effect of a polyherbal
      preparation, Zyflamend, on UBC cells resistant to cisplatin treatment. Methods:
      To establish a cisplatin-resistant human bladder cancer cell line, T24 cells were
      cultured in increasing concentrations of cisplatin for more than 10 months. These
      cells (T24R) were then treated with different concentrations of Zyflamend, and
      both proliferation and activity of nuclear factor kappaB (NFkappaB) signaling
      pathway were examined. To test the synergistic effect between Zyflamend and
      cisplatin, we treated T24R cells either with Zyflamend or cisplatin alone, or in
      combination. Apoptotic effect was evaluated by Annexin V/propidium iodide double
      staining, and the levels of the proteins involved in cell cycle and anti
      apoptosis were examined by Western blotting. Finally, mice with palpable
      xenograft were treated either with cisplatin and Zyflamend alone or in
      combination for 28 days before they were sacrificed for measuring the sizes and
      weights of the tumor tissues. In addition, proliferation and apoptosis markers
      were examined by immunohistochemistry. Results: Comparing to that in the parental
      T24 cells, NFkappaB is constitutively active in cisplatin-resistant T24R cells.
      Zyflamend is capable of inhibiting the growth of T24, T24R, as well as another
      UBC cell line J82 in a concentration-dependent manner. Mechanistically, Zyflamend
      suppresses NFkappaB-mediated cell proliferation, survival, and
      invasion/angiogenesis and induces apoptosis. In addition, Zyflamend significantly
      increased the sensitivity of T24R and J82 cells to cisplatin treatment and these
      findings were confirmed in T24R xenograft model with reduced proliferation index
      and decreased expression of RelA and its downstream target MMP9. Conclusion:
      Zyflamend is capable of counteracting bladder cancer resistance to cisplatin by
      repressing proliferation and inducing apoptosis through targeting NFkappaB
      signaling pathway.

PMID- 30104884
TI  - LINC00888 promoted tumorigenicity of melanoma via miR-126/CRK signaling axis.
AB  - Objectives: Melanoma is an aggressive skin cancer. Understanding the underlying
      mechanisms for melanomagenesis and identification of novel and effective melanoma
      treatment strategies are urgently necessary. The long-noncoding RNAs are
      considered as new essential players during cancer development, including the
      melanoma. Materials and methods: In this study, we first determined the
      expression of LINC00888 in tumor tissues and adjacent normal tissues from 28
      patients with melanoma using quantitative polymerase chain reaction, and the
      correlation between the expression level of LINC00888 and the survival months was
      also examined. Next, we investigated the effect of LINC00888 on the
      proliferation, apoptosis, and invasion in the melanoma cells. Moreover, LINC00888
      specific miRNA and target gene were further confirmed using the dual-luciferase
      reporter assay and Western blotting. Last, the tumorigenesis role of LINC00888
      was also explored using tumor xenografts mouse model. Results: Elevated LINC00888
      expression was found in melanoma specimens compared with adjacent normal tissues.
      The 4-year overall survival in melanoma patients with high expression of
      LINC00888 was substantially shorter than that in those with low expression of
      LINC00888. Knockdown of LINC00888 significantly inhibited the proliferation,
      apoptosis, epithelial-mesenchymal transition, and invasion of melanoma cells,
      while the overexpression of LINC00888 exerted opposite effect. Furthermore, we
      revealed that microRNA-126 (miR-126) was able to regulate LINC00888 expression
      and further influence the expression of CRK. Consistently, miR-126 inhibitor
      could rescue the expression of CRK in LINC00888-downregulated cells, while miR
      126 mimics could reduce the CRK expression level in cells with the overexpression
      of LINC00888. Last, the animal experiment further demonstrated that the
      overexpression of LINC00888 enhanced the tumor development in vivo. Conclusion:
      Our data showed that long-noncoding RNA LINC00888 functioned as an oncogene in
      melanoma tumorigenesis, it also regulated the cellular proliferation and invasion
      of melanoma via miR126/CRK signaling pathway and metastasis via miR-126/CRK
      signaling axis, which could be a promising molecular target for treating
      melanoma.

PMID- 30104886
TI  - Erratum: Effect of first-line endocrine therapy in patients with hormone
      sensitive advanced breast cancer: a network meta-analysis [Corrigendum].
AB  - [This corrects the article on p. 2647 in vol. 11, PMID: 29780257.].

PMID- 30104885
TI  - Outcome of eribulin as a late treatment line for Thai metastatic breast cancer
      patients.
AB  - Background: We report the safety and efficacy of eribulin as a late treatment
      line in Thai metastatic breast cancer (MBC) patients. Patients and methods: A
      total of 30 MBC patients treated with eribulin between January 2014 and January
      2017 were retrospectively analyzed. The patients were scheduled to receive 1.4
      mg/m2 of eribulin on day 1, day 8 and subsequently every 21 days. All patients
      had previously received at least three chemotherapy regimens including
      anthracycline and taxane. Response rate and progression-free survival (PFS) were
      analyzed. Results: The median age was 56 years (range, 40-74 years), with a
      median follow-up time of 5.7 months (range, 0.2-25 months). The overall response
      rate was 30% (nine patients): four patients had triple-negative breast cancer,
      three patients had luminal B breast cancer and two patients had luminal A breast
      cancer. The median PFS was 2.9 months (range, 0.2-14 months). The median number
      of previous chemotherapy regimens was 4 (range, 3-9). Univariate analysis showed
      that the number of regimens (four or fewer) prior to eribulin was statistically
      associated with superior PFS (P = 0.009). Multivariate analysis also showed
      similar statistical association between number of prior regimens (four or fewer)
      and better PFS adjusted by age group (>=50 years; hazard ratio = 1.29; 95% CI:
      1.0-1.65; P = 0.046). There were no toxic deaths or grade 4 toxicities. Nine
      (30%) patients had grade 3 anemia toxicities, and the other common toxicities
      were leukopenia and neutropenia. Four (13%) patients required dose reduction and
      16 (53%) patients required dose delay because of toxicities. Conclusion: Eribulin
      is an effective drug for heavily pretreated MBC patients with tolerable
      toxicities. The benefit was superior in patients who received fewer than four
      previous chemotherapy regimens.

PMID- 30104887
TI  - Metformin induces miR-378 to downregulate the CDK1, leading to suppression of
      cell proliferation in hepatocellular carcinoma.
AB  - : Metformin is one of the extensively and most commonly used oral
      antihyperglycemic agents, but it has been shown to exert antineoplastic effects
      in many cancer cells. Recent studies have confirmed that metformin has an
      antitumor effect on hepatocellular carcinoma (HCC). However, the molecular
      mechanism underlying this effect needs to be further studied. Materials and
      methods: CDK1 and miR-378 expression was analyzed by western blotting and real
      time PCR assays. We confirmed the association between miR-378 and CDK1 by dual
      luciferase reporter assay. The role of the miR-378/CDK1 pathway in proliferation,
      cell cycle and apoptosis was examined in vitro. The effect of miR-378 on HCC
      tumor growth was evaluated in nude xenograft mouse model. Results: Our study
      found that metformin significantly inhibited the HCC cell proliferation via
      inducing G2/M arrest. At the same time, metformin efficiently decreased CDK1
      expression and elevated miR-378 level. Moreover, the upregulation of miR-378 also
      repressed HCC cell proliferation by causing G2/M arrest and inhibited tumor
      growth. Additionally, we demonstrated that miR-378 directly targeted CDK1 3'UTR
      and downregulated CDK1 mRNA and protein levels. Furthermore, metformin treatment
      could not decrease CDK1 expression, suppress HCC cell proliferation, and induce
      G2/M cell cycle arrest. Discussion: Metformin-suppressed HCC cell proliferation
      was dependent on the inhibitory effect of miR-378 on CDK1 expression. Taken
      together, we concluded that metformin inhibited HCC cell proliferation via
      modulating miR-378/CDK1 axis. Conclusion: Collectively, the current results
      provide the first evidence, to our knowledge, that miR-378/CDK1 axis is involved
      in metformin modulating the proliferation of HCC cells, which suggests a novel
      molecular mechanism underlying the thera peutic effect of metformin on HCC.

PMID- 30104888
TI  - miR-141-3p is a key negative regulator of the EGFR pathway in osteosarcoma.
AB  - Background: Many studies have used miRNA to modulate osteosarcoma development by
      regulating protein expression, and these studies showed that the expression of
      EGFR is increased in osteosarcoma. Methods: Western blot, real-time PCR and
      immunohistochemical were used to detect the expression of EGFR and miR-141 in
      osteosarcoma tissues and cells. The correlation between miR-141 and the grading
      of osteosarcoma and the correlation with the survival time of the patients were
      analyzed. After predicting the target effect of miR-141 on EGFR by miRDB,
      correlation analysis was used to analyze the correlation between miR-141 and
      EGFR. Luciferase reporter gene, western blot and real-time PCR were used to
      detect the targeting effect of miR-141 on EGFR. Then we detected the effect of
      miR-141 on proliferation by MTT and PI staining. The effect of miR-141 on cell
      apoptosis was detected by Hochest33258 and AV-PI staining, and the effect of miR
      141 on cell migration was detected by Transwell. The regulatory effects of miR
      141 on related proteins were detected by western blot and real-time PCR. Finally,
      we transfected EGFR and EGFR DEL (mutation with miR-141 binding site) in
      osteosarcoma cells, and detected the effects of miR-141 on cell proliferation,
      apoptosis, migration and related proteins. Results: The expression of miR-141-3p
      was negatively correlated with the expression of EGFR in osteosarcoma. The
      overexpression of miR-141-3p was not only closely related to the classification
      and size of the osteosarcoma but also had a negative effect on the growth and
      migration of the osteosarcoma through negative regulation of the expression of
      EGFR. MiR-141 can inhibit the growth and metastasis of osteosarcoma cells by
      targeting EGFR and affecting its downstream pathway proteins. Conclusion: Our
      study provides miR-141-3p may be a new theoretical basis for the treatment of
      osteosarcoma.

PMID- 30104889
TI  - Efficient removal of hospital pathogens from hard surfaces by a combined use of
      bacteriophages and probiotics: potential as sanitizing agents.
AB  - Purpose: Many hospital-acquired infections (HAIs) can be transmitted by pathogens
      contaminating hospital surfaces, not efficiently controlled by conventional
      sanitation, which can indeed contribute to the selection of MDR strains.
      Bacteriophages have been suggested as decontaminating agents, based on their
      selective ability to kill specific bacteria. However, there are no data on their
      stability in detergents and their potential use in routine sanitation. On the
      other hand, a probiotic-based sanitation system (Probiotic Cleaning Hygiene
      System, PCHS) was recently shown to stably reduce pathogens on treated surfaces.
      However, its action is not specific and slow, being based on competitive
      antagonism. This work aimed to assess the effectiveness of a combined use of
      phages and PCHS in removing HAI-associated pathogens from different hard
      surfaces. Materials and methods: The decontamination ability of phages in PCHS
      was tested in vitro and in situ, against drug-susceptible or resistant
      Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains, and
      using bacterial densities similar to those detected on hospital surfaces.
      Results: Phages targeted efficiently all tested bacteria, maintaining their full
      activity when added to the PCHS detergent. Notably, the combined use of phages
      and PCHS not only resulted in a rapid reduction (up to >90%) of the targeted
      pathogens, but also, due to the stabilizing effect of probiotics, the pathogens
      were maintained at low levels (>99%) at later times too, when instead the effect
      of phages tends to diminish. Conclusion: These results suggest that a combined
      biological system might be successfully used in hospital sanitation protocols,
      potentially leading to effective and safe elimination of MDR pathogens from the
      hospital environment.

PMID- 30104890
TI  - Extremely high levels of vancomycin can cause severe renal toxicity.
AB  - Vancomycin has usually been associated with nephrotoxicity. Generally, this
      toxicity is presented as proximal tubular cells injury with or without necrosis
      and as acute interstitial nephritis. However, development of both lesions is
      uncommonly described in literature. We present a case of vancomycin-induced
      nephrotoxicity resulting in both acute interstitial nephritis and tubular cells
      damage confirmed by renal biopsy. Peak and trough levels of 77.11 and 63.60
      MUg/mL, respectively, were obtained at the first plasma determination. After 8
      more plasma determinations and several hemodialysis sessions, vancomycin levels
      were undetectable 1 month after therapy was stopped. To our knowledge, this is
      the case report with the highest vancomycin trough levels developing both lesions
      and describing total vancomycin washout after a biopsy-proven vancomycin
      toxicity. In conclusion, early vancomycin therapeutic drug monitoring should be
      performed in order to avoid toxicities where, as seen in our patient, antibiotic
      exposure could last around 1 month after last dose administration.

PMID- 30104891
TI  - High prevalence of hypervirulent Klebsiella pneumoniae infection in the genetic
      background of elderly patients in two teaching hospitals in China.
AB  - Purpose: Aerobactin is a critical factor for hypervirulent Klebsiella pneumoniae
      (hvKp) in genetic backgrounds, but data based on the genotype for the elderly is
      limited. Materials and methods: A retrospective study was conducted on elderly
      patients from June 2008 to July 2017 in 2 teaching hospitals. The clinical and
      microbiological data, including antimicrobial susceptibility testing, string
      test, extended-spectrum beta-lactamase (ESBL) production, virulence gene, and
      multilocus sequence typing, of the hvKp group defined as aerobactin positive were
      compared with those of classic K. pneumoniae isolates. Results: A total of 45.7%
      of 202 K. pneumoniae isolates were hvKp.ST23, which were predominant in 2
      hospitals, but they were not highly associated with hvKp in different hospitals.
      Hypermucoviscosity, K1, K2, magA, and rmpA/A2 genes were highly related to hvKp
      (P=0.000). With regard to the host, invasive infections (P=0.000), liver abscess
      (P=0.000), abdominal infection (P=0.000), pneumonia (P=0.037), and septic shock
      (P=0.045) were significantly higher in the elderly with hvKp. In the hvKp group,
      patients with better nutritional status were associated with a more severe
      sequential organ failure assessment score and a more serious inflammation
      reaction. Patients with diabetes (odds ratio [OR]=2.566) are more likely to be
      infected with hvKp. Previous hvKp is associated with hypermucoviscosity
      (OR=15.249) are often paralleled with hvKp. Importantly, 26% of hvKp isolates
      produced ESBLs, and most of them showed a carbapenems-resistant (CR) phenotype.
      Multivariate analysis implied that patients with a history of surgery within the
      last 1 month (OR=15.999) is an independent risk factor for CR-hvKp infection.
      Conclusion: The prevalence of hvKP is high in the elderly. ESBL-hvKp, especially
      CR-hvKp, is emerging, which is a sign that clinical awareness and infection
      monitoring needs to improve.

PMID- 30104893
TI  - Burden and risk factors of diabetes and hyperglycemia in India: findings from the
      Global Burden of Disease Study 2016.
AB  - Background: Diabetes, hyperglycemia, and their complications are a growing
      problem in India. However, no comprehensive picture of this disease burden has
      yet been presented to date. Methods: I used aggregate data from the Global Burden
      of Disease 2016 to describe the burden of diabetes and its risk factors, chronic
      kidney disease (CKD) due to diabetes, and diseases caused by high fasting plasma
      glucose from 1990 to 2016 in India. Results: Deaths due to diabetes accounted for
      3.1% (95% uncertainty interval [UI]: 2.9-3.3) of all deaths in India in 2016, up
      from 0.98% (95% UI: 0.87-1.1) of all deaths in 1990. Diabetes and hyperglycemia
      accounted for 27.5 million disability-adjusted life years in 2016, of which
      diabetes accounted for 10 million. Diabetes contributes to the causation of
      ischemic heart disease, stroke, CKD, peripheral artery disease, specific cancers,
      and tuberculosis via intermediate hyperglycemia. High body mass index, dietary
      factors (diet low in fruits, nuts and seeds, and whole grains), and tobacco use
      were the most important risk factors for diabetes. Conclusion: Diabetes and CKD
      due to hyperglycemia pose a large and increasing burden in India. Urgent programs
      and policies are needed to reduce the identified risk factors for diabetes and
      its burden.

PMID- 30104892
TI  - Effects of Spirulina platensis microalgae on antioxidant and anti-inflammatory
      factors in diabetic rats.
AB  - Objectives: Lipid peroxidation and hyperglycemia are common signs for diabetes.
      Natural antioxidants such as Spirulina platensis microalgae (SPM) may prevent
      lipid peroxidation and hyperglycemia. This study aimed to evaluate the effects of
      SPM on antioxidant and anti-inflammatory in diabetic rats. Materials and methods:
      Sixty-four rats were divided into eight groups (n=8) and orally treated with 0,
      10, 20 and 30 mg/kg body weight of SPM extract. Experimental groups included
      diabetic rats fed with 0 (DC), 10, 20 and 30 mg/kg SPM. Healthy rats were treated
      with 0 mg/kg SPM (HC), 10 mg/kg SPM, 20 mg/kg SPM and 30 mg/kg SPM. At the end of
      the trial, blood samples were collected and the plasma concentrations of trace
      minerals (TMs), biochemical parameters, and antioxidant enzymes in liver were
      evaluated. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF
      alpha (tumor necrosis factor-alpha) and IL-6 (interleukin-6) were evaluated.
      Results: Our findings showed that diabetes significantly lowered the plasma
      concentration of TMs and antioxidant enzymes in liver and also increased the
      levels of malondialdehyde, glucose, lipid profile, AST, ALT, TNF-alpha and IL-6
      (DC vs HC). However, an oral supplement of SPM (20 and 30 mg/kg body weight)
      lowered levels of malondialdehyde level, glucose, lipid parameters, AST, ALT, TNF
      alpha and IL-6. The same levels increased the plasma contents of zinc, iron,
      copper and selenium and activity of antioxidant enzymes (P<0.05). Conclusion: It
      can be concluded that diabetes decreases TM concentration and antioxidant enzymes
      and also increases lipid profile, glucose, AST, ALT, TNF-alpha and IL-6
      concentrations. Inclusion of SPM supplementing (20 and 30 mg/kg body weight)
      increased some TMs and antioxidant enzymes. SPM may provide TMs for synthesis of
      antioxidant enzymes which subsequently reduce lipid profile, glucose
      concentration and anti-inflammatory responses.

PMID- 30104894
TI  - Safety and efficacy of duloxetine in Japanese patients with chronic knee pain due
      to osteoarthritis: an open-label, long-term, Phase III extension study.
AB  - Purpose: To assess long-term safety, tolerability, and efficacy of duloxetine in
      Japanese patients with chronic knee pain due to osteoarthritis. Methods: In this
      open-label extension study (NCT02335346), Japanese patients with knee
      osteoarthritis and pain (Brief Pain Inventory [BPI] - Severity average pain score
      >=4 at start of randomized trial) who had previously received duloxetine 60
      mg/day or placebo for 14 weeks in a double-blind randomized trial entered the
      extension and received duloxetine 60 mg/day for 48 weeks. The primary outcome was
      safety/tolerability, secondary outcomes were change in BPI-Severity (BPI-S)
      average pain, BPI-Interference (BPI-I), Patient Global Impression-Improvement
      (PGI-I), Clinical Global Impression-Improvement (CGI-I), 36-item Short-Form
      Health Survey (SF36), and Western Ontario and McMaster Universities
      Osteoarthritis Index (WOMAC), and exploratory outcomes were knee range of motion
      (efficacy outcome) and Kellgren-Lawrence grade (safety outcome). Results: Of 323
      patients who completed the randomized trial, 93 (50 placebo, 43 duloxetine)
      entered the extension. Most patients (85, 91.4%) experienced an adverse event,
      most commonly constipation, nasopharyngitis, somnolence, and dry mouth (>=10% of
      patients). There were eight serious adverse events in seven patients and no
      deaths. No obvious duloxetine-related changes were observed in laboratory tests,
      vital signs, or electrocardiograms. The change from baseline in BPI-S average
      pain score was significant throughout the extension. Significant reductions in
      BPI-I, PGI-I, CGI-I, WOMAC, and SF36 scores were also maintained through 52
      weeks. There were no substantial changes in range of motion or Kellgren-Lawrence
      grade. Conclusion: In Japanese patients with chronic knee pain due to
      osteoarthritis, long-term treatment with duloxetine was well tolerated and
      associated with sustained improvements in pain and health-related quality of life
      without radiographic deterioration.

PMID- 30104895
TI  - Comparison of percutaneous intradiscal ozone injection with laser disc
      decompression in discogenic low back pain.
AB  - Background: Intervertebral disc herniation with the pressure on the surrounding
      neural structures is one of the most important causes of chronic low back pain,
      which sometimes leads to open surgery. Reducing the pressure inside the disc with
      intradiscal intervention such as laser irradiation or ozone injection is a
      minimally invasive method and an alternative to surgery with satisfactory
      results. These two methods were compared with each other in this research.
      Patients and methods: In this clinical trial, 40 patients with back pain
      radiating to lower limb due to lumbar intervertebral disc herniation were
      selected. These patients were randomly divided into two equal groups for
      percutaneous intradiscal intervention. The Laser Disc Decompression Group (LDG)
      (n=20) was exposed to 1500 J of laser irradiation into the disc center. In the
      Ozone Injection Group (OZG) patients (n=20), 6 mL of ozone 30 ug/mL was injected
      into the center of the disc. Considering the level of neural root involvement,
      both groups received 20 mg of triamcinolone injection via transforaminal
      epidural. Patients were followed up for 12 months regarding score on visual
      analogue scale and life performance improvement based on Oswestry Disability
      Index (ODI) and satisfaction level. Results: According to the results, no
      difference was found between the two groups for ODI variable before intervention,
      whereas OZG showed better ODI scores in the measured time intervals. In LDG, only
      a significant difference in terms of ODI score was found between the times of
      before surgery and the first month. Conclusion: Intradiscal ozone injection could
      be an effective and cost-effective method for treatment of patients with
      discogenic back pain.

PMID- 30104896
TI  - Personal experience and attitudes of pain medicine specialists in Israel
      regarding the medical use of cannabis for chronic pain.
AB  - Introduction: The scientific study of the role of cannabis in pain medicine still
      lags far behind the growing use driven by public approval. Accumulated clinical
      experience is therefore an important source of knowledge. However, no study to
      date has targeted physicians who actually use cannabis in their daily practice.
      Methods: Registered, active, board-certified pain specialists in Israel (n=79)
      were asked to complete a Web-based survey. The survey was developed using the
      Qualtrics Online Survey Software. Questions were formulated as multiple-choice
      questions, and these addressed three areas of interest: 1) doctors' personal
      experience; 2) the role of cannabis in pain medicine; and 3) cannabis
      medicalization and legalization. Results: Sixty-four percent of all practicing
      pain specialists in Israel responded. Almost all prescribe cannabis. Among them,
      63% find cannabis moderately to highly effective, 56% have encountered mild or no
      side effects, and only 5% perceive it as significantly harmful. Common
      indications are neuropathic pain (65%), oncological pain (50%), arthralgias
      (25%), and any intractable pain (29%). Leading contraindications are
      schizophrenia (76%), pregnancy/breastfeeding (65%), and age <18 years (59%). Only
      12% rated cannabis as more hazardous than opiates. On a personal note, 45% prefer
      cannabis for themselves or a family member. Lastly, 54% would like to see
      cannabis legalized in Israel. Conclusion: In this survey, pain clinicians
      experienced in prescribing cannabis over prolonged periods view it as an
      effective and relatively safe treatment for chronic pain, based on their own
      experience. Their responses suggest a possible change of paradigm from using
      cannabis as the last resort.

PMID- 30104897
TI  - Sudden onset flank pain: a case report of retroperitoneal hemorrhage secondary to
      a ruptured adrenal hemangioma.
AB  - Background: Acute abdominal pain is a common complaint of patients presenting at
      the emergency department (ED). It can be caused by a broad spectrum of diseases.
      Providing care for patients with acute abdominal pain requires familiarity with
      the epidemiology, prevalence, and presentation of abdominal pathology, as well as
      a working knowledge of the differential diagnoses. Case report: In this article,
      we discuss a case of spontaneous rupture of adrenal hemangioma with large
      retroperitoneal hemorrhage in a 31-year-old female. Discussion: Emergency
      physicians regularly encounter uncommon causes of abdominal pain. Spontaneous
      rupture of adrenal hemangioma is an extremely rare cause of abdominal pain, but
      proper understanding of the disease process will aid clinicians to make a final
      diagnosis and ensure appropriate treatment. In this study, presentations and risk
      factors for spontaneous, atraumatic rupture of adrenal hemangioma as well as ED
      management and definitive treatment options are discussed.

PMID- 30104898
TI  - Pooling analysis on prognostic value of PHH3 expression in cancer patients.
AB  - Background: Various studies have evaluated the significance of phosphohistone-H3
      (PHH3) expression in cancer patients, but controversy over its reliability
      remains. We conducted a meta-analysis to summarize the prognostic relevance of
      PHH3 expression in cancer patients. Patients and methods: Nineteen studies,
      including 4803 patients, were identified by searching PubMed, Web of Science,
      Embase, and Cochrane Library. The correlation of PHH3 expression level with
      overall survival (OS), disease-free survival, and recurrence-free survival was
      analyzed. Results: Overall, the results suggest that high expression of PHH3 can
      predict a poor OS (HR=2.66, 95% CI=1.74-4.08, P<0.001), disease-free survival
      (HR=3.40, 95% CI=1.47-7.87, P=0.004), and recurrence-free survival (HR=2.80, 95%
      CI=1.61-4.85, P<0.001) in cancer patients. The subgroup analysis showed that
      highly expressed PHH3 was significantly related to breast cancer (HR=5.66, 95%
      CI=2.72-11.78, P<0.001) and urogenital tumors (HR=3.01, 95% CI=1.78-5.09,
      P<0.001). Furthermore, no significant difference was found between Asian
      (HR=1.98, 95% CI=1.08-3.63, P=0.026) and Caucasian populations (HR=3.01, 95%
      CI=1.87-4.85, P<0.001) regarding OS and PHH3 expression. Conclusion: This meta
      analysis indicates that high expression of PHH3 may serve as a biomarker for poor
      prognosis in patients with cancer.

PMID- 30104899
TI  - P-TNM staging system for colon cancer: combination of P-stage and AJCC TNM
      staging system for improving prognostic prediction and clinical management.
AB  - Aim: This study focused on improving the American Joint Committee on Cancer TNM
      staging system and demonstrated an improvement in prognostic accuracy and
      clinical management of colon cancer using the P-TNM staging system. Patients and
      methods: Eligible patients (N=56,800) were identified from the Surveillance,
      Epidemiology, and End Results database between January 1, 2010, and December 31,
      2014. The P-stage (P0 or P1) was assigned to each patient based on age at
      diagnosis, tumor grade, and tumor size. The outcome of interest was cancer
      specific survival (CSS). The Cox proportional hazards regression analyses were
      used to identify independent prognostic factors and analyze the CSS probabilities
      of patients with colon cancer having different P-TNM stages, respectively.
      Results: A total of 29,627 patients were assigned to P0-stage and 27,173 patients
      were assigned to P1-stage. The P1-stage was associated with a 98.1% increased
      risk of cancer-specific mortality (hazard ratio =1.981, 95% confidence interval
      =1.891-2.076, P<0.001), which was higher in patients with nonmetastatic colon
      cancer. The P1-stage patients had improvement in CSS compared with those in P0
      stage in respective stages (P<0.001). Moreover, CSS decreased in stage I-P1
      compared with stage IIA-P0 or IIIA-P0 (P<0.001), stage IIIA-P1 compared with
      stage IIA-P0 (P<0.001), stage IIB-P1 compared with stage IIIB-P0 or IIC-P0
      (P<0.001), stage IIIB-P1 compared with stage IIC-P0 (P<0.001), and stage IIC-P1
      compared with stage IIIC-P0 (P<0.001). Conclusion: P-stage was an independent
      prognostic factor for colon cancer. This study strongly supported the
      incorporation of P-stage into the American Joint Committee on Cancer TNM staging
      system for a better approach to prognostication and, thus, more individualized
      risk-adaptive therapies in colon cancer.

PMID- 30104900
TI  - Human leukocyte antigen gene polymorphisms are associated with systemic
      inflammation in hepatitis B virus-related hepatocellular carcinoma.
AB  - Background: Systemic inflammation (SI) is associated with tumor progression and
      overall survival (OS) in patients with hepatocellular carcinoma (HCC). The
      presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte
      antigen (HLA) region can influence the prognosis of patients with hepatitis B
      virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed
      to analyze the correlations between HLA gene polymorphisms and SI. Patients and
      methods: This study included 330 patients with HCC. The clinical parameters were
      reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and
      rs7768538, were genotyped using the MassARRAY system. Results: The rs3997872,
      rs7453920, and rs7768538 genotypes were found to be significantly associated with
      OS (P<0.05). The rs7453920 genotype was significantly associated with the
      neutrophil/lymphocyte ratio (NLR; P=0.001), which was used as an SI index with a
      threshold determined by receiver operating characteristic analysis. An elevated
      NLR was also an independent predictor of OS according to univariate and
      multivariate analyses (P<0.001). Conclusion: Our data show that HLA gene
      polymorphisms are associated with SI in patients with HBV-related HCC, and the
      absence of minor allele A (rs7453920) promotes SI and shortens OS.

PMID- 30104902
TI  - Vitamin D and orthodontics: an insight review.
AB  - Vitamin D is known as the oldest of all hormones. 7-Dehydrocholesterol is
      converted to previtamin D3. It becomes a secosteroid when it is later converted
      to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). A number of factors influence vitamin
      D3 production, including skin pigmentation, the use of sunscreen lotions, season,
      latitude, and altitude. Vitamin D is important for bone metabolism and calcium
      hemostasis. Researchers have linked a deficiency in vitamin D levels to a number
      of systemic complications, including cardiovascular disease, diabetes, immune
      deficiency, and infectious diseases. In orthodontics, laboratory studies have
      revealed some evidence that vitamin D enhances tooth movement and the stability
      of the tooth position. This review is an attempt to understand the role and
      systemic consequences of vitamin D deficiency and to examine its relevance to
      orthodontics.

PMID- 30104901
TI  - Targeting energy metabolism to eliminate cancer cells.
AB  - Adaptive metabolic responses toward a low oxygen environment are essential to
      maintain rapid proliferation and are relevant for tumorigenesis. Reprogramming of
      core metabolism in tumors confers a selective growth advantage such as the
      ability to evade apoptosis and/or enhance cell proliferation and promotes tumor
      growth and progression. One of the mechanisms that contributes to tumor growth is
      the impairment of cancer cell metabolism. In this review, we outline the small
      molecule inhibitors identified over the past decade in targeting cancer cell
      metabolism and the usage of some of these molecules in clinical trials.

PMID- 30104903
TI  - Evaluation of antiretroviral effect on mitochondrial DNA depletion among HIV
      infected patients in Bali.
AB  - Background: Nucleoside reverse transcriptase inhibitors (NRTIs) are the
      cornerstone of highly active antiretroviral therapy combination regimens for HIV
      infection. Unfortunately, NRTIs have been noticeably associated with many adverse
      effects related to mitochondrial toxicity leading to mitochondrial
      deoxyribonucleic acid (mtDNA) depletion. However, similar mitochondrial
      dysfunction has recently been found even in antiretroviral therapy-naive
      patients, suggesting HIV itself could contribute to this abnormality. In this
      study, we determine whether mtDNA depletion was present in either antiretroviral
      therapy-naive or NRTI-treated patients at Sanjiwani Hospital, Bali, Indonesia.
      Patients and methods: A cross-sectional study was conducted from the peripheral
      blood mononuclear cells of HIV patients. Specifically, the relative content of
      mtDNA (mtRNR1 gene) to nuclear DNA (ASPOLG gene) was determined by real-time
      polymerase chain reaction. Data were analyzed with SPSS 16.0 software and
      GraphPad Prism 7.02. Results: A total of 84 samples (67 on NRTIs and 17 HIV
      naive) were suitable for analysis. We identified 21.4% of the samples (18/84)
      with mtDNA:nDNA ratio <1. Although it was not significant (P=0.121), the median
      mtDNA:nDNA ratio of HIV-naive group was slightly higher (median 1.8;
      interquartile range [IQR]: 1.1-2.1) than NRTI-treated patients (median 1.5; IQR:
      1.3-2.85). Tenofovir-based NRTI was more frequently used (73.13%) than zidovudine
      based NRTI (26.86%). The period for which NRTI was used probably contributed to
      the ratio of mtDNA:nDNA. The median ratio of mtDNA:nDNA zidovudine-treated
      patients was slightly lower (median 1.2; IQR: 1.08-1.98) when compared to
      tenofovir-based NRTI (median 1.6; IQR: 1.05-2.10), with the median period of
      former treatment being significantly longer (P<0.001). Although these data
      overall indicate that NRTI treatment had no effect on mtDNA:nDNA ratios, patients
      who undergo more than 12 months of NRTIs treatment show a decrease in the ratio;
      however, further study is required. Conclusion: Almost one-fourth of the samples
      showed a lower mtDNA:nDNA ratio. The decreasing of the ratio mtDNA:nDNA was most
      likely present after 12 months of NRTI treatment.

PMID- 30104904
TI  - Current treatment options for postmenopausal vaginal atrophy.
AB  - Vulvovaginal atrophy (VVA) is a silent epidemic that affects up to 50%-60% of
      postmenopausal women who are suffering in silence from this condition. Hormonal
      changes, especially hypoestrogenism inherent in menopause, are characterized by a
      variety of symptoms. More than half of menopausal women are concerned about the
      symptoms of VVA, such as dryness, burning, itching, vaginal discomfort, pain and
      burning when urinating, dyspareunia, and spotting during intercourse. All these
      manifestations significantly reduce the quality of life and cause discomfort in
      the sexual sphere. However, according to research, only 25% of patients with the
      symptoms of VVA receive adequate therapy. This is probably due to the lack of
      coverage of this problem in the society and the insufficiently active position of
      specialists in the field of women's health regarding the detection of symptoms of
      VVA. Many patients are embarrassed to discuss intimate complaints with a
      specialist, which makes it difficult to verify the diagnosis in 75% of cases, and
      some patients regard the symptoms of VVA as manifestations of the natural aging
      process and do not seek help. Modern medicine has in the arsenal various options
      for treating this pathological condition, including systemic and topical hormone
      replacement therapy, the use of selective estrogen receptor modulators, vaginal
      dehydroepiandrosterone, use of lubricants and moisturizers, as well as non-drug
      therapies. Timely diagnosis and adequately selected therapy for the main symptoms
      of VVA lead to restoration and maintenance of the vaginal function and vaginal
      health.

PMID- 30104906
TI  - Intraoperative severe suprachoroidal air as a complication of 23-gauge vitrectomy
      combined with air-fluid exchange.
AB  - We reported a rare case of sudden onset of severe but reversible suprachoroidal
      air that occurred at the moment of air-fluid exchange in 23-gauge vitrectomy. A
      31-year-old male patient presented with a large break at 10-11 o'clock and high
      bullous, nearly total retinal detachment. He underwent first surgery with silicon
      oil injection at the end of the surgery. He was arranged to have a second surgery
      for silicon oil removal through pars plana vitrectomy which was performed
      smoothly at first. While switching to another mode of air-fluid exchange to clean
      the residual emulsified oil droplets, surgical view disappeared completely and
      was suddenly replaced with severe and total suprachoroidal air, which fortunately
      resolved within 3 days without any other severe complications.

PMID- 30104907
TI  - Vismodegib and orbital excision for treating locally advanced basal cell
      carcinoma.
AB  - Purpose: Orbital invasion of periocular basal cell carcinoma (BCC) is a
      potentially life-threatening condition with high levels of ocular morbidity.
      Exenteration results in significant disfigurement and permanent loss of vision.
      We report our experience with a patient who presented with medial orbit invasion
      of a BCC following 2 previous microscopically adequate local excisions of medial
      canthal BCC, an adequate Moh's micrographic surgical excision of the tumor, and
      radiotherapy. The patient underwent an orbital excision where the tumor was found
      to have perineural involvement and extend beyond the posterior margin. Following
      the pathology results of this procedure, the patient opted to try vismodegib
      (Erivedge(r)) to delay exenteration for as long as possible. Observations: A
      course of vismodegib was taken by the patient with minor side effects (partial
      alopecia, mild dysgeusia and hyposmia, and minor muscle cramps). Subsequent
      imaging demonstrated no recurrence of the orbital tumor 29 months after orbital
      excision. Conclusion and importance: We demonstrate the use of vismodegib with
      local orbital excision as an eye-saving alternative to exenteration for advanced
      orbital metastasis of BCC.

PMID- 30104905
TI  - Remission of nephrotic syndrome after surgical intervention for bronchogenic
      carcinoma: the 10-year follow-up of a patient with membranous nephropathy.
AB  - Nephrotic syndrome (NS) is a pivotal manifestation of glomerular injury
      associated with various types of neoplasms. It may either precede or act as the
      presenting feature of the disease, whereas membranous nephropathy (MN) is a major
      phenotype of paraneoplastic glomerulopathies. However, there is a lack of
      information regarding the remission from paraneoplastic NS due to MN in patients
      who achieve favorable long-term survival after the successful removal of
      malignant tissue. We, herein, describe a case of biopsy-proven MN in a 65-year
      old male patient with bronchogenic carcinoma, which was found during the systemic
      workup for concurrent NS. He was successfully treated with thoracoscopic left
      lower lobectomy and achieved a complete remission from NS at approximately 10
      months after radical surgery. In 10 years of follow-up, there has been no
      recurrence of the pulmonary cancer and the patient is doing well with no relapse
      of NS, despite having never received treatment with any type of immunomodulating
      agent. Several concerns, including diagnostic management and therapeutic
      strategies for paraneoplastic NS, are discussed.

PMID- 30104908
TI  - Patterns of injuries and predictors of inhospital mortality in trauma patients in
      Saudi Arabia.
AB  - Background: The aim of this study was to describe the pattern of traumatic
      injuries and determine the predictors of inhospital mortality in patients
      admitted to the emergency department. Patients and methods: This is a
      retrospective cohort study of 3,786 patients with traumat injuries admitted to
      the emergency department of King Abdulaziz Medical City, Riyadh, Saudi Arabia,
      between January 2012 and December 2014. Data on patient characteristics, trauma
      characteristics and outcomes were extracted from medical records. A negative
      binomial regression model was utilized to identify significant predictors of
      inhospital mortality. Results: Of all injured patients, 77.5% were male, 29.8%
      were aged 15-25 years and 25.7% were aged 26-45 years. Blunt trauma was the main
      mechanism of injury, including motor vehicle crashes (MVCs) in 52.0% and falls in
      25.8% of patients. Most patients had injuries to the extremities (61.3%),
      followed by the head (32.2%), chest (16.9%) and abdomen (8.9%). Injuries were
      mild in 49.7% of patients, moderate in 30.2% and severe in 20.1%. The sex of the
      patients was significantly associated with the mechanism of injury (p<0.001),
      severity (p<0.001), anatomical site of injury (p<0.001), admission to the
      intensive care unit (p<0.001), need for trauma team activation (p<0.001) and type
      of transportation to hospital (p<0.001). The predictors of inhospital mortality
      were age (rate ratio [RR] for each 10-year increase=1.174; p<0.001), falls and
      burns (RR=2.337 and 1.728; p<0.001) and moderate and severe injuries (RR=6.438
      and 181.780; p<0.001). Conclusion: Our results suggest different patterns of
      trauma injuries according to patient age and sex. MVCs were the leading cause of
      injuries, but falls and burns had the highest inhospital mortality. This suggests
      the need for a comprehensive national education and prevention programs that
      address all causes of injuries.

PMID- 30104909
TI  - How much further for the sub-2-hour marathon?
AB  - The sub-2-hour marathon is a new barrier in endurance running performance, and it
      has been widely debated in the scientific community. In this review we present a
      mathematical model to estimate the possible year when a male could break through
      the sub-2-hour barrier, and also an estimation of when a female could break Paula
      Radcliffe's marathon running record. Further, we present several aspects (ie,
      physiology, nationality, age, biomechanics, pacing, and drafting) that are
      associated with marathon running performance in elite runners and, finally, the
      possible characteristics of the male to break the sub-2-hour barrier. In summary,
      with the results of the developed equations, it is possible that a male athlete
      can break through the sub-2-hour barrier in the next decade (with Nike(r)
      Breaking2 performance 1920-2018 [NBP]: y =0.0417x2-14.18x +3,128; year of 2026;
      without NBP 1920-2018: y =0.045x2-15.12x +3,194; year of 2027). This marathoner
      will possibly have a maximal oxygen uptake >85 mL?kg-1?min-1 and should perform
      the race at a pacing higher than 85% of maximal oxygen uptake. In addition, this
      runner should pay more attention to strength training, endurance strength, speed
      training, and focus on running training at an intensity above the anaerobic
      threshold. Most likely, this runner originates from East Africa (especially from
      Ethiopia) and will have an age of ~27 years. For the females, there is poor
      evidence regarding the physiological profile of the female marathoner who will
      break Radcliffe's record, but the available literature suggests that it will not
      happen any time soon.

PMID- 30104910
TI  - Influence of oncology nurses' empathy on lung cancer patients' cellular immunity.
AB  - Background: Medical staff's empathy is closely related to patients' outcome. This
      research aimed to verify the influence of Chinese oncology nurses' empathy on the
      cellular immunity of lung cancer patients. Materials and methods: The study
      included 365 lung cancer patients, who were attended by 30 oncology nurses
      between October 2016 and May 2017. At the time of admission and discharge, flow
      cytometric analysis was used to measure the cellular immunity of patients,
      including T-cell subsets and natural killer (NK)-cell activity. The level of
      empathy of the oncology nurses was measured by the Jefferson Scale of Empathy
      (JSE, Chinese version). The nurses were divided into high, moderate, and low
      empathy groups based on JSE scores. Associations between the empathy shown by
      nurses and the cellular immunity of patients were examined. Results: On
      admission, there was no statistical difference in the cellular immunity of the
      patients taken care of by the three groups of nurses (P>0.05). At discharge,
      patients whose nurses were in the high empathy group reported significantly
      higher B-cell and NK-cell percentages than those whose nurses were in the low
      empathy group (P<0.001). There was a positive correlation between nurse empathy
      and percentage of B cells (P=0.003) and NK cells (P<0.001), but no correlation
      was found between empathy and percentage of CD3+, CD4+, and CD8+ cells. Multiple
      linear regression analyses indicated that nurse empathy significantly contributed
      to patient percentage of B cells and NK cells after controlling for patient
      demographics, disease conditions, and lifestyle. Conclusion: The effect of
      oncology nurses' empathy on cellular immunity was confirmed in lung cancer
      patients, suggesting empathy education, such as narrative medicine education,
      should be strengthened to improve patient outcome.

PMID- 30104911
TI  - Bidirectional relationships between psychological health and dermatological
      conditions in children.
AB  - Dermatological conditions are common among children. They are a frequent cause of
      presentation to health care services and a leading contributor to burden of
      disease. Evidence supports the notion that bidirectional relationships exist
      between children's physical and psychological health, whereby the child's
      dermatological condition can impact their psychological health and well-being,
      while, in the reverse direction, psychological factors (eg, stress) can impact
      the severity and course of the child's skin disease. The psychological impact of
      dermatological conditions in childhood needs to be taken into account during the
      assessment, planning, and treatment phases of management. Likewise, the potential
      effect of children's emotional and behavioral difficulties on management,
      particularly in terms of the impact on parents' ability to implement their
      child's treatment plan, should be considered. This literature review summarizes
      the current evidence for the relationships between three common chronic
      dermatological conditions of childhood - atopic dermatitis, psoriasis, and
      urticaria - and psychological adjustment and quality of life in childhood.
      Overall, a general paucity of research in the pediatric context - combined with
      limitations in terms of study design, variability in operationalization of
      constructs, and heterogeneity in measurement of outcomes - makes it difficult to
      draw firm conclusions in this area. Based on the available research, implications
      for successful long-term management of these conditions are discussed in terms of
      integrating psychological and parenting support with medical management to
      improve adherence, reduce disease severity, and improve quality of life for
      children and their families.

PMID- 30104912
TI  - Retinal imaging with optical coherence tomography: a biomarker in multiple
      sclerosis?
AB  - Multiple sclerosis (MS) is a progressive neurological disorder characterized by
      both inflammatory and degenerative components that affect genetically susceptible
      individuals. Currently, the cause of MS remains unclear, and there is no known
      cure. Commonly used therapies tend to target inflammatory aspects of MS, but may
      not halt disease progression, which may be governed by the slow, subclinical
      accumulation of injury to neuroaxonal structures in the central nervous system
      (CNS). A recognized challenge in the field of MS relates to the need for better
      methods of detecting, quantifying, and ameliorating the effects of subclinical
      disease. Simply stated, better biomarkers are required. To this end, optical
      coherence tomography (OCT) provides highly reliable, reproducible measures of
      axonal damage and neuronal loss in MS patients. OCT-detected decrements in
      retinal nerve fiber layer thickness and ganglion-cell layer-inner plexiform layer
      thickness, which represent markers of axonal damage and neuronal injury,
      respectively, have been shown to correlate with worse visual outcomes, increased
      clinical disability, and magnetic resonance imaging-measured burden of disease in
      MS patients. Recent reports have also suggested that OCT-measured microcystic
      macular edema and associated thickening of the retinal inner nuclear layer
      represent markers of active CNS inflammatory activity. Using the visual system as
      a putative clinical model in MS, OCT measures of neuroaxonal structure can be
      correlated with functional outcomes to help us elucidate mechanisms of CNS injury
      and repair. In this review, we evaluate evidence from the published literature
      and ongoing clinical trials that support the emerging role of OCT in diagnosing,
      staging, and determining response to therapy in MS patients.

PMID- 30104913
TI  - Clinical utility of ledipasvir/sofosbuvir in the treatment of adolescents and
      children with hepatitis C.
AB  - Chronic infection with hepatitis C virus (HCV) affects an estimated 0.1%-2% of
      the pediatric population in the United States. While the clinical course in young
      children is indolent, adolescents who contract HCV have a disease course similar
      to adults, with a 26-fold increased risk of chronic liver disease-associated
      mortality, hepatocellular carcinoma, and need for curative liver transplantation.
      Furthermore, adolescent patients are entering childbearing age and carry a risk
      of passing HCV to their offspring via vertical transmission. Pegylated-interferon
      (PEG-IFN) with ribavirin was previously the only treatment option for pediatric
      patients with chronic hepatitis C (CHC), but the high likelihood of adverse
      reactions and subcutaneous route of administration limited its use and efficacy.
      Recently, the direct-acting antivirals (DAAs) ledipasvir (LDV) and sofosbuvir
      (SOF) were approved for adolescents with CHC. This review discusses the natural
      history of CHC in pediatric patients, data supporting LDV/SOF in adolescents, and
      ongoing studies evaluating DAAs in pediatric patients.

PMID- 30104914
TI  - Revision of the World species of the genus Chromoteleia Ashmead (Hymenoptera,
      Platygastridae, Scelioninae).
AB  - The genus Chromoteleia Ashmead is revised. Twenty-seven species are recognized,
      of which six species are redescribed: C.congoana (Risbec), C.connectens Kieffer,
      C.fuscicornis Kieffer, C.longitarsis Kieffer, C.semicyanea Ashmead, C.tricarinata
      Kieffer; and twenty-one species are described as new: C.aequalis Chen & Johnson,
      sp. n., C.alternata Chen & Johnson, sp. n., C.bidens Chen & Masner, sp. n.,
      C.copiosa Chen & Johnson, sp. n., C.cuneus Chen & Johnson, sp. n., C.curta Chen &
      Johnson, sp. n., C.depilis Chen & Johnson, sp. n., C.dispar Chen & Masner, sp.
      n., C.feng Chen & Johnson, sp. n., C.fossa Chen & Johnson, sp. n., C.ingens Chen
      & Masner, sp. n., C.levitas Chen & Johnson, sp. n., C.longa Chen & Johnson, sp.
      n., C.maura Chen & Masner, sp. n., C.parvitas Chen & Johnson, sp. n., C.pilus
      Chen & Johnson, sp. n., C.plana Chen & Johnson, sp. n., C.rara Chen & Johnson,
      sp. n., C.robusta Chen & Johnson, sp. n., C.semilutea Chen & Johnson, sp. n.,
      C.sparsa Chen & Johnson, sp. n.Chromoteleiarufithorax Kieffer remains a valid
      species, but its identity and status are unclear. All species are known only from
      the Neotropical region except for Chromoteleiacongoana (Resbec) which only occurs
      in Africa.

PMID- 30104915
TI  - A Comparative Analysis of Tooth Size Discrepancy between Male and Female Subjects
      Presenting with a Class I Malocclusion.
AB  - Objectives: To evaluate the tooth size discrepancy and Bolton's ratios between
      male and female subjects with a Class I malocclusion. Materials and Methods: The
      digital e-models of 100 male and 100 female 12-year-old southern Chinese children
      with a Class I malocclusion were selected. The mesiodistal widths from permanent
      first molar to the contralateral side first molar of the upper and lower
      dentitions were measured. Differences between the tooth size discrepancy,
      together with the anterior and overall Bolton's ratios between male and female
      subjects, were assessed using a two-sample t-test. A paired t-test was used to
      determine differences between antimetric pairs of teeth within the same arch.
      Results: Females had statistically significant smaller teeth than males (P <
      0.05) except the upper left and lower left lateral incisor and lower left and
      right central incisors. The mean values of anterior Bolton's ratios for males and
      females were 77.04 and 77.03, respectively (P > 0.05), while the mean values of
      overall Bolton's ratios of male and female are 90.48 and 90.65, respectively (P <
      0.05). The clinical significant differences (Cohen's d > 0.2) for contralateral
      tooth size were shown on the maxillary canines, lateral incisors, and central
      incisors of males; and mandibular canines and lateral incisors of females.
      Conclusions: Southern Chinese females presenting with Class I malocclusions have
      smaller mesiodistal tooth dimensions compared to males. Both males and females
      presented several tooth size asymmetries. There are no statistical differences in
      anterior and overall Bolton's ratios between the genders.

PMID- 30104916
TI  - How Prepared Are We for Possible Bioterrorist Attacks: An Approach from Emergency
      Medicine Perspective.
AB  - Preparedness for bioterrorist attacks and early recognition of specific agents
      are essential for public health. Emergency departments may play an important role
      in this field. The large spectrum of bioterrorism involves not only disastrous
      terrorism with mass casualties, but also microevents using low technology but
      producing civil unrest, disruption, disease, disabilities, and death. It aims not
      only to cause mortality and morbidity, but also to lead to social and political
      disruption. Preparedness appears to be the most potent defense against possible
      bioterrorist events. In this article, we aim to create awareness against
      biological agents and underline the importance of emergency departments in this
      public health problem.

PMID- 30104918
TI  - Leland G. Hawkins, MD-His Life and Orthopaedic Legacy: Talus Fractures and the
      Hawkins Classification.
AB  - The long history of excellence and continued success of the University of Iowa
      Department of Orthopedics and Rehabilitation is due to the dedication and talent
      of generations of faculty, residents and staff. Many former Iowa Orthopedic
      residents have made significant contributions and become leaders in Orthopedic
      surgery. An orthopedic surgeon and scholar with roots at the University of Iowa
      deserving of tribute is Dr. Leland Greene Hawkins. His seminal investigation and
      interest in fractures of the talus established the well-known Hawkins
      Classification for talar neck fractures, which revolutionized treatment and
      quantified the risk of progression to avascular necrosis, earning him attention
      and respect worldwide.

PMID- 30104919
TI  - The Economic Burden of Residency Interviews on Applicants.
AB  - Background: The residency match is increasingly competitive. The interview is an
      essential component, yet little has been documented about the costs applicants
      incur during the interview process and it is unclear how they manage these
      expenses. Objective: The purpose of this study was to define the economic burden
      of residency interviews for United States (U.S.) allopathic students
      participating in the 2016 Main Residency Match. We hypothesized that the
      financial burden of residency interviews varies based on specialty and plays a
      role in the applicant's ability to participate in all desired interviews.
      Methods: A 26 question electronic survey was developed following pilot study of
      applicants to a single residency program. Following validation, the survey was
      distributed to administrative officials at all U.S. allopathic medical schools
      for circulation to senior students. Results were pooled for statistical analysis.
      Results: We received responses from 759 U.S. allopathic seniors. A single
      interview most commonly costs $250 - $499. Most applicants incurred substantial
      interview related costs. Sixtyfour percent of respondents spent at least $2,500,
      while 13% spent $7,500 or more. Specialty competitiveness was predictive of
      higher interview costs. Seventy-one percent of respondents borrowed money to fund
      interview costs, and 41% declined interviews for financial reasons. Conclusions:
      Senior medical students incur substantial costs to participate in residency
      interviews, often adding to already burdensome educational debt. We encourage
      residency programs, especially those in competitive specialty fields, to pursue
      cost reduction strategies. Additionally, medical schools should provide financial
      counseling to allow students to anticipate interview costs.

PMID- 30104920
TI  - Mycobacterium Tuberculosis Monoarthritis of the Knee in Children: A Case Report.
AB  - : Mycobacterium tuberculosis monoarthritis is a rare form of TB, occurring in 1
      2% of cases in the United States. Delays in definitive diagnosis and subsequent
      treatment are common. While case reports of tuberculous arthritis have been
      presented in international literature, there is a relative paucity of literature
      from within the United States. Given the difficulty in diagnosis and adverse
      outcomes of delayed diagnosis, we present the case of an 11-year-old otherwise
      healthy male with isolated monoarticular TB septic arthritis of the right knee. A
      discussion, including review of current literature, regarding presentation,
      diagnosis, and treatment of tuberculous monoarthritis follows. The emerging role
      of arthroscopy as a diagnostic and treatment modality for tuberculous
      monoarthritis of the knee is discussed. LEVEL OF EVIDENCE: VI.

PMID- 30104917
TI  - Healthcare Professional's Perception of Patient Safety Measured by the Hospital
      Survey on Patient Safety Culture: A Systematic Review and Meta-Analysis.
AB  - Objective: To assess the culture of patient safety in studies that employed the
      hospital survey on patient safety culture (HSOPS) in hospitals around the world.
      Method: We searched MEDLINE, EMBASE, SCOPUS, CINAHL, and SciELO. Two researchers
      selected studies and extracted the following data: year of publication, country,
      percentage of physicians and nurses, sample size, and results for the 12 HSOPS
      dimensions. For each dimension, a random effects meta-analysis with double
      arcsine transformation was performed, as well as meta-regressions to investigate
      heterogeneity, and tests for publication bias. Results: 59 studies with 755,415
      practitioners surveyed were included in the review. 29 studies were conducted in
      the Asian continent and 11 in the United States. On average studies scored 9 out
      of 10 methodological quality score. Of the 12 HSOPS dimensions, six scored under
      50% of positivity, with "nonpunitive response to errors" the lowest one. In the
      meta-regression, three dimensions were shown to be influenced by the proportion
      of physicians and five by the continent where survey was held. Conclusions: The
      HSOPS is widely used in several countries to assess the culture of patient safety
      in hospital settings. The culture of culpability is the main weakness across
      studies. Encouraging event reporting and learning from errors should be
      priorities in hospitals worldwide.

PMID- 30104921
TI  - Bone Mineral Density T-Scores Derived from CT Attenuation Numbers (Hounsfield
      Units): Clinical Utility and Correlation with Dual-energy X-ray Absorptiometry.
AB  - Background: Clinical computed tomography (CT) studies performed for other
      indications can be used to opportunistically assess vertebral bone without
      additional radiation or cost. Reference values for young women are needed to
      evaluate diagnostic accuracy and track changes in CT bone mineral density values
      across the lifespan. The purpose of this study was to determine reference values
      for lumbar trabecular CT attenuation (Hounsfield units [HU]) and determine the
      diagnostic accuracy of HU T-scores (T-scoreHU) for identifying individuals with
      osteoporosis. Methods: We performed a retrospective single-center cohort study of
      patients undergoing CT of the lumbar spine. Reference values for lumbar spine
      Hounsfield units were determined from a reference sample of 190 young women aged
      20-30 years undergoing CT scan of the lumbar spine. A separate sample of 252
      older subjects undergoing CT and dual-energy X-ray absorptiometry (DXA) within a
      6-month period that served as a validation cohort. Osteoporosis was defined by T
      scoreDXA <= -2.5. Reference values were determined for lumbar HU from L1 to L4
      from the reference cohort (24.0 +/- 2.9 years). T-scoreHU was calculated in the
      validation cohort (58.9 +/- 7.5 yrs). Receiver operating characteristic (ROC)
      curves were used to assess sensitivity and specificity of T-scoreHU for this
      task. Results: Reference group HU ranged from 227 +/- 42 at L3 to 236 +/- 42 at
      L1 (P < 0.001). Validation group T-scoreDXA was -0.7 +/- 1.5 and -0.9 +/- 1.2 at
      lumbar and femoral sites respectively. Mean T-scoreHU was -2.3. T-scoreHU of 
      3.0, corresponding to 110 HU, was 48% sensitive and 91% specific for osteoporosis
      in the validation group. ROC area under the curve ranged from 0.825 to 0.853
      depending on lumbar level assessed. Conclusions: Although lumbar trabecular HU T
      scores are lower than DXA T-scores, thresholds can be selected to achieve high
      sensitivity and specificity when screening for osteoporosis. Patients with a
      lumbar T-scoreHU <= -3.0 should be referred for additional evaluation. Further
      research into HU T-scores and clinical correlates may also provide a tool to
      assess changes in vertebral bone and the relationship to fracture risk across the
      lifespan.

PMID- 30104922
TI  - Overuse of Magnetic Resonance Imaging in the Diagnosis and Treatment of Moderate
      to Severe Osteoarthritis.
AB  - Background: MRI in the evaluation of end-stage knee joint osteoarthritis (OA) is
      usually unnecessary when radiographic and clinical evidence of gonarthrosis is
      clear. The purpose of this study was to assess the prevalence of MRI scans
      ordered in patients with radiographically obvious gonarthrosis and to examine the
      characteristics of health care providers who ordered these imaging studies.
      Methods: We retrospectively identified 164 patients diagnosed with moderate to
      severe OA who were referred for total knee replacement (TKA) over a one-year
      period. The percentage of patients who had an MRI scan with or without X-ray,
      within the preceding 3 months prior to referral, were calculated. Subgroups were
      analyzed to identify characteristics that may influence the decision to order an
      MRI, including K-L grade, provider type, level of training, and practice
      location. Results: Of 145 patients, 19 (13.1%) presented with an MRI scan.
      Between the number of MRI scans ordered, there was a significant difference when
      comparing physicians versus non-physicians, with physicians ordering less MRI
      scans (p=0.018). There was a significant difference when comparing non-academic
      versus academic, with academic providers ordering less MRI scans (p=0.044). There
      was no significant difference with fellowship training or provider proximity to
      our academic institution. Conclusions: In this study, 13.1% of patients with
      radiographically obvious knee OA obtained an MRI prior to referral for TKA. Non
      physicians and non-academic physicians were more likely to order MRI scans.
      Improved education for referring providers may be necessary to decrease overuse
      of MRI in the diagnosis of moderate to severe arthritis. Level of Evidence: Level
      II.

PMID- 30104923
TI  - Evaluation of Orthopaedic Trauma Fellowship Web Sites and an Assessment of 21
      Content Domains.
AB  - Background: A program's web site can attract or deter fellowship applications. It
      can also impact applicants' final rank lists. Web-based information may allow
      applicants to apply more selectively, decreasing interview costs for themselves
      and programs. The accessibility and content of program web sites for several
      orthopaedic subspecialties have been analyzed for inadequacies. The goal of this
      study was to perform an analysis for the web sites of orthopaedic trauma
      fellowships. Methods: A list of accredited orthopaedic trauma fellowships was
      obtained from the Orthopaedic Trauma Association (OTA) Fellowship Directory. Web
      site accessibility was determined by presence of a functional hyperlink in the
      directory and the web site's searchability using Google(r). Web site content was
      evaluated based on 21 criteria. Results: 53 programs were identified, offering 84
      positions. 27 had web sites accessible through the OTA fellowship directory via
      functioning links. 19 additional web sites were accessible using Google(r). Seven
      programs lacked web sites entirely. Web site content varied between programs.
      Over half of the web sites lacked information for 13 of the 21 content criteria.
      A complete list of results can be located in Table 1. Conclusions: Inadequacies
      exist in the accessibility and content of OTA accredited Orthopaedic Trauma
      Fellowship web sites. We draw attention to 21 standard content areas pertinent to
      applicants that could be considered by the OTA and individual programs to include
      on their respective web sites. Standardization across web sites may allow for a
      more direct comparison between programs and improve the match process. Level of
      Evidence: Review Article.

PMID- 30104924
TI  - Unintentional Firearm Injuries Remain Prevalent Over a 12 Year Experience at a
      Rural Midwestern Level 1 Trauma Center.
AB  - Recently, firearm injuries in the United States have taken center stage in
      political debates and in the media. Much of the past epidemiological research on
      firearm injuries has focused primarily on the urban landscape. This study was
      undertaken to highlight the unique spectrum of firearm injuries seen at a rural
      level 1 trauma center to provide insight into prevalence, mechanism of injury,
      and seasonal variation. An IRB-approved retrospective study was performed of the
      trauma registry at a rural Level 1 hospital to identify all patients with firearm
      injuries from January 2002 to May 2014. Data obtained for each patient included
      demographics, injury date, a brief injury summary, and results of drug/ alcohol
      screening. Chart review was performed to confirm accuracy of the database and
      descriptive statistics were calculated to compare subgroups. During the 12 year
      study period, 408 patients with firearm injuries were treated at our hospital.
      There were 360 males and 48 females. Ages ranged from an infant to 90 years.
      Handguns were the most common type of firearm (49%). Mortality in this series was
      19%. The median age for fatal and non-fatal wounds was 44 and 27 years,
      respectively. The three main causes of injury were accidental (36%), self
      inflicted (33%), and assault (26%). Alcohol and drugs were commonly present.
      Hunting incidents accounted for 26% of accidents and most of these occurred while
      deer hunting in November and December. The demographics and mechanism of firearm
      injuries vary across the urban-rural continuum and it is important to identify
      these subgroups so targeted interventions can be pursued.

PMID- 30104926
TI  - The Telescoping Hip Plate for Treatment of Femoral Neck Fracture: Design
      Rationale, Surgical Technique and Early Results.
AB  - Recent estimates suggest an annual incidence of greater than 125,000 femoral neck
      fractures. Surgical treatment is indicated for the majority of these fractures,
      which are estimated to double by the year 2050. Most displaced femoral neck
      fractures in elderly patients are treated with arthroplasty secondary to high
      complication rates associated with internal fixation. Traditional implants used
      for internal fixation, typically in elderly patients with stable fracture
      morphology and younger patients regardless of morphology, include the sliding hip
      screw (SHS), with or without a supplemental anti-rotation screw, and multiple
      cancellous lag screws. Complications have been reported with both of these
      fixation techniques, especially as they apply to treating displaced femoral neck
      fractures in the elderly. Yet, complications of nonunion, loss of fixation and
      osteonecrosis, among others, still frequently occur in stable patterns of femoral
      neck fracture treated with internal fixation. Accordingly, additional implants
      have been designed recently to improve outcomes and avoid such complications in
      this population. The Targon Femoral Neck Plate (Aesculap, Tuttlinger, Germany)
      has been used in Europe for the treatment of both displaced and nondisplaced
      femoral neck fractures by combining a side plate and multiple cancellous lag
      screws. Multiple studies have shown superior rates of both nonunion and
      osteonecrosis when compared to the SHS and multiple cancellous screws in both
      displaced and nondisplaced femoral neck fractures. This article details the
      design rationale, surgical technique and early postoperative results of a new
      hybrid implant used for the treatment of both displaced and nondisplaced femoral
      neck fractures.

PMID- 30104925
TI  - Do Orthopedic Trauma Surgeons Adhere to AAOS Guidelines when Treating Distal
      Radius Fractures?
AB  - Background: The American Academy of Orthopedic Surgeons (AAOS) has provided
      Clinical Practice Guidelines (CPG) and Appropriate Use Criteria (AUC) regarding
      management of distal radius fractures. The purpose of this study was to evaluate
      current practices in management of distal radius fractures among orthopedic
      trauma surgeons and to examine adherence to the AAOS criteria. Methods: An online
      survey was posted and distributed via the Orthopaedic Trauma Association (OTA)
      website. Information collected included demographics, injury management, and case
      based questions. For all cases, surgeons were asked to select their treatment of
      choice given the same fracture in a 25-year-old patient and a 65-year-old
      patient. Results were compared between surgeons with < 10 years of practice
      experience and those with > 10 years of experience. Results: There was a total of
      51 survey respondents. 45% had <10 years in practice, while 55% had > 10 years in
      practice. All respondents reported routine use of preoperative radiographs, while
      26% reported routine use of preoperative computed tomography (CT) scans. 73% of
      respondents reported that they perform operative adjunct fixation of associated
      ligamentous injuries at the time of distal radius fracture fixation. No one used
      wrist arthroscopy or fixed associated ulnar styloid fractures. 69% did not allow
      any range of motion in the immediate postoperative period, while the remainder
      allowed active and/ or passive ROM. 20% routinely used Vitamin C for Complex
      Regional Pain Syndrome (CRPS) prophylaxis postoperatively. 59% routinely used
      physical and/ or occupational therapy postoperatively. For case-based scenarios,
      respondents generally tended towards operative fixation in younger patients
      compared to older patients with the same fracture type. Surgeons with < 10 years
      in practice and those with > 10 years in practice varied significantly in terms
      of preoperative imaging and operative fixation of associated ligamentous injuries
      at the time of fracture fixation. Conclusions: When compared to the AAOS CPG and
      AUC, orthopedic trauma surgeons generally followed accepted treatment guidelines.
      Differing practices between surgeons with <10 years in practice compared to those
      with >10 years in practice may be reflective of what is taught in residency
      training programs.

PMID- 30104927
TI  - Set it and Forget it: Diaphyseal Fractures of the Humerus Undergo Minimal Change
      in Angulation After Functional Brace Application.
AB  - Objectives: To quantify radiographic changes observed in humeral shaft frctures
      throughout course of treatment with functional bracing. Design: Retrospective
      cohort study. Setting: Level 1 Trauma Center and affiliated Tertiary Care Center.
      Patients: 72 retrospectively identified patients with fracture of the humeral
      diaphysis. Intervention: Application of functional brace with radiographs
      obtained immediately after brace application and at 1 week, 2 weeks, 3 weeks, 6
      weeks, 3 months, 6 months and 12 month follow-up.Main Outcome Measure: Fracture
      angulation, measured in the coronal and sagittal planes. Results: 522 radiographs
      from 72 patients were critically reviewed. All fractures were followed to
      healing. Sixty-six patients (92%) successfully healed their fractures with non
      operative treatment. The average angulation on immediate post-brace X-ray was 12
      degrees varus ad 7 degrees procurvatum. At final follow-up, average coronal
      angulation was 14 degrees and 4 degrees procurvatum. Fracture angulation changed
      a mean 2 degrees in the AP plane and 3 degrees in the sagittal plane over the
      course of care. Linear regression determined fracture angulation proceeds toward
      both varus and recurvatum at 0.01 degrees per day. Conclusion: Humeral shaft
      fractures treated non-operatively heal with minimal change in angulation after
      brace application. If angulation on the post-brace radiograph is acceptable and
      there is no history of repeat trauma and no cosmetic deformity, radiographs may
      be utilized less frequently. Patients should be evaluated via history and
      physical exam at follow-up prior to the 6-week point, at which time regular
      radiographs (6 week, 3 month, 6 month, 12 month) should commence.

PMID- 30104928
TI  - The Effect of Different Combinations of Three Stacked Half-Hitches and Suture
      Materials on an Arthroscopic Knot in a Dry or Wet Environment.
AB  - Purpose: Evidence is lacking on the effect of different combinations of three
      stacked half-hitches and suture materials on the loop/ knot security of an
      arthroscopic knot under cyclic loading conditions. The specific aim of this study
      was to identify variables, such as stacked half-hitch configurations, suture
      materials, and testing environments, that affect knot strength and loop security
      under cyclic loading conditions. Methods: Two suture materials (Orthocord and
      ForceFiber) were used to tie five differently stacked reversing half-hitches on
      alternating posts (RHAP) in an arthroscopic knot condition. All knots were
      evaluated in both dry and wet cyclic loading tests. Results: Knots tied with
      three identical half-hitches stacked on the same post (Conf #1) resulted in 100%
      knot slippage regardless of suture material in dry environment. In the wet
      environment this knot configuration performed slightly better (ForceFiber: 20%
      survived; Orthocord: 40% survived). With knots tied with one of the half-hitches
      in the RHAPs reversed, a significant improvement occurred in knot holding
      compared to Conf #1 (p<0.05). Knots tied with the last half-hitches in the RHAPs
      reversed using ForceFiber were 100% secure in both test environments; whereas
      those tied with Orthocord had 70% and 80% security rates in the respective
      environments. Knots tied with two half-hitches of the RHAPs reversed demonstrated
      the best overall performance. Conclusion: Significant effects for both stacked
      half-hitch configurations and suture materials on the knot loop and knot security
      were observed. Caution should be used when tying the 3 RHAPs in a knot using
      standard arthroscopic techniques. This study may provide a solution that might
      improve the maximum failure loads observed between orthopaedic surgeons, and
      achieve better clinical outcomes. Clinical Relevance: The findings of this study
      indicate the importance of three reversing half-hitches on alternating posts in
      performing arthroscopic knot tying, and provide evidence regarding discrepancies
      of maximum clinical failure loads observed between orthopaedic surgeons leading
      to better surgical outcomes.

PMID- 30104929
TI  - Ganglion Cyst as a Rare Complication of Hip Arthroscopy Resolved With THA: A Case
      Report.
AB  - Background: A rare complication of hip arthroscopy is the development of a
      ganglion cyst. These cysts can affect structures surrounding the hip joint. In
      some cases, the femoral artery may be involved, leading to claudication or a
      pulsatile mass that can resemble an aneurysm. Case Description: We present the
      case of a 62 year-old male who complains of 3 months of right hip pain. Workup
      reveals a degenerative labrum with cam impingement. After a discussion of various
      treatment options, the patient elected for arthroscopy to correct the
      impingement. An anterior capsulotomy was created to establish access to the
      joint. Cam decompression was indicated to address the impingement. The patient
      developed a recurring ganglion cyst following the procedure that was not
      permanently prevented with cyst aspiration. Total hip arthroplasty with ganglion
      cyst decompression resolved the ganglion cyst and resolved the hip pain.
      Conclusions: This is the first case report that describes the development of a
      ganglion cyst following hip arthroscopy. Arthroplasty and ganglion cyst
      decompression in the presence of degenerative joint disease presents a viable
      treatment option for these cysts. Additionally, this case suggests interportal
      capsulotomy closure may prevent ganglion cyst development and should be
      considered when performing hip arthroscopy.

PMID- 30104930
TI  - Does Closure of the Capsule Impact Outcomes in Hip Arthroscopy? A Systematic
      Review of Comparative Studies.
AB  - Introduction: Arthroscopic management of the hip capsule has become a topic of
      debate in recent literature. Few comparative studies exist to help establish
      clear treatment recommendations. Methods: Utilizing the Preferred Reporting Items
      for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review
      of the literature was conducted using PubMed, CINAHL, EMBASE, sportDiscus (EBSCO)
      and Cochrane Central Register of Controlled Trials databases by two independent
      investigators. Comparative studies evaluating outcomes after two or more distinct
      treatment approaches to capsule management were included. Results: The review
      yielded 7 articles that met inclusion criteria. Outcomes included in the review
      include patient reported outcome measures (mHHS, HOS, NASH) in 5 articles, return
      to sport in 1 article, and formation of postoperative heterotopic ossification
      (HO) in 1 article. In two articles evaluating the outcomes of revision hip
      arthroscopy, plication was associated with > 10 point improvements in HOS-ADL and
      mHHS scores when compared to no plication. The literature is inconclusive
      regarding routine hip capsule closure in primary arthroscopy, with one study
      supporting the practice, and one study showing no difference; capsular closure
      may help accelerate return to sports and improve outcomes while decreasing
      revisions in cases of borderline dysplasia. Closure does not influence HO rates
      after surgery. Conclusion: There is insufficient evidence in the present
      literature to suggest routine closure of inter-portal capsulotomies after primary
      hip arthroscopy impacts patient outcomes. Capsular closure or plication should be
      given strong consideration in revision cases. Complete closure or plication may
      influence outcomes in patients with borderline dysplasia, for athletes wishing to
      return to sport, and in cases of extensile capsulotomies, although the data are
      inconclusive. Prospective, high level studies are indicated to create evidence
      based treatment recommendations for capsular management in hip arthroscopy.

PMID- 30104931
TI  - Combined Femoral-Sciatic Nerve Block is Superior to Continuous Femoral Nerve
      Block During Anterior Cruciate Ligament Reconstruction in the Pediatric
      Population.
AB  - Background: Despite advancements in minimally invasive arthroscopic surgical
      techniques, post-operative pain management following ACL reconstruction remains a
      concern. This study compares the effectiveness of two common intraoperative pain
      management strategies - a femoral nerve catheter (FC) versus a combined femoral
      nerve catheter and single injection sciatic nerve block (FSB) - in pediatric
      patients undergoing ACL reconstruction. Methods: The medical records of patients
      age 8 to 18 who underwent ACL reconstruction at our institution were reviewed
      retrospectively. All subjects underwent general anesthesia with either FC or FSB.
      Multivariable linear regression, or modified Poisson regression were used to
      compare outcome variables across groups. Propensity scores were used to minimize
      bias due to the non-randomized allocation of the regional anesthesia protocol.
      Results: The study population included 18 subjects in the FC group and 32
      subjects in the FSB group. There was no difference in incidence of nausea or
      opioid prescription refill requests between groups. Total intravenous (IV)
      morphine equivalent dose, maximum numerical rating scale (NRS) pain score, and
      percentage of subjects requiring one or more opioid doses in the PACU were
      significantly greater in the FC group relative to the FSB group. PACU length of
      stay (LOS) was also significantly greater in the FC group than the FSB group.
      Conclusion: This study suggests that FSB may be a more effective pain management
      technique for reducing the total IV morphine equivalent dose, maximum NRS pain
      scores, number of PACU postoperative opioid doses, and PACU LOS following ACL
      reconstruction in the pediatric population.Level of Evidence: III.

PMID- 30104932
TI  - In Vivo Toxicity of Local Anesthetics and Corticosteroids on Supraspinatus
      Tenocyte Cell Viability and Metabolism.
AB  - Background: This study was conducted to evaluate the effects of commonly used
      injection medication combinations on supraspinatus tenocyte cell viability and
      tissue metabolism. Methods: Twenty adult dogs underwent ultrasound guided
      injection of the canine equivalent of the subacromial space, based on random
      assignment to one of four treatment groups (n=5/group): normal saline, 1.0%
      lidocaine/methylprednisolone, 1.0% lidocaine/triamcinolone or 0.0625%
      bupivacaine/triamcinolone. Full-thickness sections of supraspinatus tendon were
      harvested under aseptic conditions and evaluated on days 1 and 7 post-harvest for
      cell viability and tissue metabolism. Data were analyzed for significant
      differences among groups. Results: Tendons exposed to 1% lidocaine/
      methylprednisolone had significantly lower cell viability at day 1 as compared to
      all other groups and control. All local anesthetic/ corticosteroid combination
      groups had decreased cell viability at day 7 when compared to the control group.
      Conclusions: This study demonstrated significant in vivo supraspinatus
      tenotoxicity following a single injection of combination local anesthetic/
      corticosteroid when compared to saline controls. Level of Evidence: Level II.

PMID- 30104933
TI  - Efficacy and Validation of a Simulation-Based Compartment Syndrome Instructional
      Course.
AB  - Background: This study reports the validity and effectiveness of a simulation
      based compartment syndrome instructional course. Methods: Six post-graduation
      year one (PGY1) orthopaedic residents and six PGY5 residents participated in the
      study. All PGY1 residents participated in a four-hour compartment syndrome
      training simulation. An anatomic compartment model was used to test needle
      placement accuracy in four leg muscle compartments. Pre-training, immediate post
      training, and one-month post-training performance data were collected from all
      PGY1 residents, as well as data from a onetime assessment of all PGY5 residents.
      These assessments included a paper test for lower leg anatomy (anatomy module), a
      procedural test of needle placement accuracy using an anatomic compartment
      syndrome simulation module (needle placement module), and an assessment of
      ability to measure compartment pressure via low cost simulation (pressure
      measurement module). Face validity of the needle placement module and pressure
      measurement module were assessed using a structured questionnaire given to all 12
      study participants and three orthopaedic faculty. Results: The PGY1 residents
      demonstrated significant improvement at immediate post-training in all three
      assessments compared to their pre-training performances (anatomy p=0.019, needle
      placement p=0.026, pressure measurement p=0.033 and Objective Structured
      Assessment of Technical Skill (OSATS) score for pressure measurement p <0.0001).
      This performance was maintained at the one-month post-training assessment.
      Immediate post-training and one-month post-training PGY1 resident performances
      were comparable with PGY5 resident performance in all tests.Fifteen participants
      rated the face validity of the needle placement and pressure measurement modules.
      For the needle placement module, 73.3% of participants highly rated (4 out of 5
      or greater) for realism, 86.7% highly rated for being an effective tool for
      teaching, and 80% highly rated for needing the model to be available throughout
      their training. The pressure measurement module did not receive high face
      validity ratings. Conclusions: With minimal, inexpensive training, the
      performance of junior residents in a compartment syndrome simulation was improved
      to a level comparable with senior residents. In addition, this performance was
      maintained at one-month post-training. The compartment syndrome anatomic module
      had highly-rated face validity. Clinical Relevance: Training junior residents to
      accurately diagnose compartment syndrome using a realistic simulation may allow
      for greater diagnostic accuracy in the clinical setting.

PMID- 30104934
TI  - The Significance of a "Close" Margin in Extremity Sarcoma: A Systematic Review.
AB  - Background: An important measure of successful sarcoma treatment is the surgical
      tumor margin, yet defining and reporting the tumor margin has remained a source
      of controversy. Our study sought to determine whether there is a need to be more
      specific in classifying a margin by distinguishing a 'close' margin, or if simply
      calling a margin positive or negative is sufficient. Methods: We performed a
      comprehensive literature search in which all studies were reviewed independently
      by two separate reviewers. Studies eligible for inclusion and data analysis
      consisted of those that reported on at least ten patients with a primary sarcoma
      of the extremities who received limb-salvage or amputation surgery with a report
      of the final surgical margin as well as the histologic grade. Only studies that
      provided local recurrence outcomes with a minimum follow-up of two years were
      included. Results: Our literature search and article exclusion process resulted
      in 22 articles that contained 498 patients for data analyses. We found that the
      Enneking classification system distinguishes between intralesional, marginal, and
      wide/ radical margins, and that a close margin behaves closer to a positive
      margin than a negative margin. When all tumors were analyzed, a marginal margin
      gave a recurrence rate of 50.48% compared to an intralesional margin recurrence
      rate of 75.76% and a wide/ radical margin of 7.22%. A marginal margin set to a
      positive margin gave the highest sensitivity compared to comparing marginal
      margins to wide and intralesional margins alone. This was also observed when
      tumors were stratified into high-grade osteosarcomas treated with chemotherapy.
      In addition, we found that chemotherapy dramatically reduced local recurrence
      rates in osteosarcoma. Conclusions: Our literature search and data analysis
      showed that the Enneking classification system was able to give more information
      on local recurrence compared to a simple dichotomous system, and therefore may be
      considered a more successful predictor of treatment outcomes. As a result, this
      investigation may lead a suggestion of a practice-changing proposal of how
      surgical margins in sarcoma should be reported universally amongst multiple
      disciplines and institutions.Level of Evidence: II.

PMID- 30104935
TI  - What are the Results of Surgical Treatment of Postoperative Wound Complications
      in Soft Tissue Sarcoma? A Retrospective, Multi-Center Case Series.
AB  - Background: Non-oncologic wound complications are common following resection of
      soft tissue sarcomas and factors predisposing to the development of complications
      have been extensively studied. To our knowledge, the methods and results of
      surgical treatment of these complications have not been reported. The purposes of
      this study were to 1) identify time to recognition, treatment employed, and
      eventual outcome of complications 2) investigate risk factors that may predispose
      patients to failure in management of complications following resection of soft
      tissue sarcomas. Methods: This was a multi-institutional, retrospective case
      series of patients treated with a primary closure of a limb sparing resection of
      a soft tissue sarcoma of the pelvis or extremity who developed a non-oncologic
      wound complication requiring operative intervention. The primary outcomes were a
      healed wound at the end of treatment and the total number of procedures required
      to address the complication. Results: There were 61 patients from 11 institutions
      included in the analysis. The median time from surgery to the initial recognition
      of a complication was 22 days (range 0-173 days), with 51 patients (84%)
      presenting in the first six weeks postoperatively. The definitive procedures
      included primary closure (44), healing by secondary intention (9), muscle flap
      (6), and skin graft (2). No patient was treated with an amputation. Six patients
      (10%) had a wound requiring continued dressing changes. 12 patients (20%)
      required at least one (range 1-4) additional unplanned procedure. In a bivariate
      analysis, we found patients with an infection were at increased risk of requiring
      multiple unplanned procedures (p=0.024). Conclusion: Limb sparing resection of a
      soft tissue sarcoma is known to be at high risk of postoperative wound
      complications. We found that complications uncommonly present greater than six
      weeks after initial treatment and surgical management predictably results in
      retention of the affected limb and a healed wound in those requiring operative
      treatment.Level of Evidence: 4 - Case Series.

PMID- 30104936
TI  - Radiologic Evaluation of the Distal Radius Indices in Early And Late Childhood.
AB  - The osseous anatomy of the distal radius is well documented in adults. Three
      commonly discussed variables are the volar tilt (also known as palmar tilt or
      palmar inclination), radial inclination, and radial height. These values are not
      well defined in the growing skeleton. We studied the radiographic measurements of
      normal distal radius osseous anatomy in children and identified how these values
      change with age. 372 patients (215 males and 157 females) between the ages of 8
      and 16 were included in the study. Normal values of volar tilt, radial
      inclination, and radial epiphyseal height were defined for each age group.
      Regression analysis showed that volar tilt increased significantly by increase in
      age (P <0.001). Radial inclination and radial epiphyseal height both showed
      significant increase with increase in age (P<0.001). This is the first study to
      define these radiographic values in children and their change with age.

PMID- 30104937
TI  - Opening Wedge Osteotomy for the Correction of Adolescent Tibia Vara.
AB  - Background: Tibia vara, or Blount's disease, is a pathologic angular deformity of
      upper tibial physis causing a bow leg deformity. Adolescent Blount's disease may
      be unilateral or bilateral and is diagnosed during or just before the adolescent
      growth spurt. In addition to predisposing genetic factors, biomechanical overload
      of the proximal tibial physis causes asymmetric growth leading to a varus
      deformity.Surgical intervention is usually required for adolescent Blount's
      disease. Hemiepiphysiodesis has had some success in arresting or correcting the
      deformity. Tibial osteotomy can achieve correction acutely with internal or
      external fixation or gradually with external fixation.This article reports the
      outcomes of correcting adolescent tibia vara with a proximal opening wedge
      osteotomy (POWO) and internal fixation in nine patients with a primary diagnosis
      of Adolescent Blount's Disease. Methods: We conducted a retrospective review of
      patients treated with POWO between April 2007 and July 2015. Fifty charts were
      selected using ICD9 codes for tibia vara and CPT codes for osteotomy. Nine
      patients (11 tibia) meeting eligibility criteria were identified. In addition to
      pre-operative data; operative factors, such as blood loss; and post-operative
      outcomes such as radiographic accuracy of correction, time to healing, time to
      full weight-bearing, number of office visits and complication rates were
      collected. Results: Pre-operative radiographic measurements showed the varus
      deformity was primarily tibial. Post-operative correction demonstrated a mean
      correction of 17.64 degrees  (range, 7 degrees -26 degrees ). Patients returned
      to full weight bearing status around 67 days after surgery and required very few
      follow-up visits during the course of treatment. Three of nine patients
      experienced complications including seroma requiring drainage, metallosis
      mistaken for infection leading to hardware removal, and a wound abscess treated
      with antibiotics (one patient each). No patients lost correction, experienced
      nerve palsy, compartment syndrome nor complained of leg length discrepancy.
      Conclusions: Proximal opening wedge osteotomy (POWO) is a reproducible, safe and
      effective technique for correction of adolescent tibia vara, with potential
      advantages of fewer return visits and sooner return to weight bearing than
      external fixation. In select patients, it is a useful alternative to external
      fixation or closing wedge osteotomy.Level of Evidence: IV.

PMID- 30104938
TI  - Factors that Predict Overall Health and Quality of Life in Non-Ambulatory
      Individuals with Cerebral Palsy.
AB  - Background: It is unknown what role specific tasks associated with personal care,
      positioning, communication and social interaction, and comfort and emotions play
      in predicting the overall health and quality of life of individuals with non
      ambulatory cerebral palsy (CP). In this study, we prospectively evaluated which
      of these factors were significant predictors of overall health and quality of
      life. Methods: Parents and guardians of non-ambulatory children, adolescents and
      young adults with CP were prospectively recruited from the Cerebral Palsy Clinic
      of a large pediatric academic hospital. Caregivers completed the CP Child
      Questionnaire(r). Univariate analyses were used to identify relationships between
      overall health, overall quality of life (QOL), and responses in the following
      categories: personal care and activities of daily living, positioning and
      transfer mobility, comfort and emotions, and communication and social
      interaction. Significant predictors of overall health and QOL were then
      determined via logistic regression. Results: 64 patients ages 0-20 years and
      Gross Motor Function Classification System levels IV and V were included in our
      study (mean age 9.16 +/-4.96 years). Overall QOL (OR 194.2, 95% CI, 9.5-3964.9)
      and comfort while sitting (OR 15.9, 95% CI, 1.2-205.3) were significant
      predictors of overall health. Feelings of unhappiness or sadness (OR 59.9, 95%
      CI, 1.6-2209.8), difficulty understanding the parent or guardian (OR 29.8, 95%
      CI, 1.6-543.7), and not attending school (OR 57.2, 95% CI, 2.6-1274.4) were
      significant predictors of lower overall quality of life. Conclusions: Overall QOL
      appears to predict overall health. Factors associated with comfort and emotions
      and communication and social interaction appear to predict overall QOL to a
      greater extent than personal care and transfer mobility.Level of Evidence:
      Prognostic II.

PMID- 30104939
TI  - Crossed K-Wires Versus Intramedullary Headless Screw Fixation of Unstable
      Metacarpal Neck Fractures: A Biomechanical Study.
AB  - Background: Intramedullary headless screw (IMHS) has shown promise as an
      alternative to other fixation devices for metacarpal neck fractures. The purpose
      of this study was to assess the biomechanical performance of IMHS versus the
      commonly-used crossed K-wire technique. We hypothesized that IMHS fixation
      provides superior stability to K-wires. Methods: A metacarpal neck fracture model
      in 23 human cadaveric metacarpals was created. The specimens were divided into
      two groups based upon fixation method: Group 1, 3 mm intramedullary headless
      screw; and Group 2, 0.045 inch crossed K-wires. A cantilever bending model was
      used to assess load-to-failure (LTF), maximum displacement, energy absorption,
      and stiffness. Results: The mean LTF was 70.6 +/- 30.1 N for IMHS and 97.5 +/-
      34.7 N for crossed K-wires. Mean stiffness was 11.3 +/- 3.4 N/mm and 17.7 +/- 7.8
      N/mm for IMHS and crossed K-wires, respectively. The mean maximum displacement
      was 20.2 +/- 4.6 mm for IMHS and 24.1 +/- 3.7 mm for crossed K-wires. Moreover,
      mean energy absorption was 778.3 +/- 528.9 Nmm and 1095.9 +/- 454.4 Nmm,
      respectively, for IMHS and crossed K-wires. Crossed K-wires demonstrated
      significantly higher stiffness and maximum displacement than IMHS (p < 0.05).
      Conclusions: IMHS fixation of unstable metacarpal neck fractures offers less
      stability compared to crossed K-wires when loaded in bending. Clinical Relevance:
      Crossed K-wires offer superior stability for the treatment of metacarpal neck
      fractures. These results reveal that IMHS fixation is less favorable
      biomechanically and should be cautiously selected with regards to fracture
      stability.

PMID- 30104940
TI  - Single Forearm Vessel Injury in a Perfused Hand: Repair or Ligate? A Systematic
      Review.
AB  - Background: The purpose of this study was to systematically review available
      literature reporting vessel patency and how this correlates with cold symptoms
      following the treatment of a single forearm artery injury when the hand remains
      perfused. The outcomes of those treated by ligation were compared to those
      treated with vessel repair. Methods: Electronic databases including PubMed,
      Embase (Elsevier) and Cochrane Central Register of Controlled Trials (Willey)
      were searched for studies that reported the outcomes of patients who underwent
      either ligation or repair of single vessel injuries to hands that remained
      perfused at time of presentation. Level of evidence was determined by two
      independent reviewers. Studies were then sorted based on Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and
      application of inclusion and exclusion criteria. A total of 19 studies were
      included for statistical analysis. The patency of repaired vessels was calculated
      (with comparison between those with radial versus ulnar repair) as was the
      prevalence of cold symptoms in both ligation (or repairs that went on to
      occlusion) and repair groups. Results: The average patency of radial and ulnar
      artery repairs was 68.39% and 65.56% respectively. There was no significant
      difference between the success rates of these repair groups (pooled estimates for
      odd ratios was 1.02, p=0.867). The average incidence of cold symptoms in those
      who underwent ligation (or repair that when on to occlusion) and those that had
      patent repairs were 19.82% and 17.27% respectively. There was no significant
      difference between the incidence of cold symptoms between these groups (pooled
      estimate for proportion of patients with cold symptoms was 0.223, p=0.573).
      Conclusions: This review showed there to be no significant difference in patency
      of isolated radial or ulnar artery repairs. There was also no significant
      difference in the prevalence of cold sensitivity in patients who underwent vessel
      ligation compared to those who underwent repair (and subsequently remained
      patent). These results support the conclusion of there being no clear benefit to
      attempting repair of a single vessel, although further studies are needed given
      the often incomplete reporting of clinical outcomes in this patient population.
      Additionally, though a cost-benefit analysis was not included in this review,
      exploring this aspect of the decision making process could be valuable.Level of
      Evidence: IV.

PMID- 30104941
TI  - Trends and Costs of Anterior Cervical Discectomy and Fusion: a Comparison of
      Inpatient And Outpatient Procedures.
AB  - Study Design: Epidemiologic Study. Objectives: To identify the trends in
      utilization of outpatient discharge for single level anterior cervical discectomy
      and fusion (ACDF), between 2007 and 2014, and to compare the costs and incidence
      of complications against a cohort of inpatients. Methods: We retrospectively
      reviewed 18,386 patients from the PearlDiver database from between 2007 and 2014.
      Discharge status was determined from billing codes. The total cost of all
      procedures and diagnostic tests, was determined for the global period from the
      time of diagnosis up until 90-days post-operatively, and the incidence of
      complications was recorded for 30-days. Results: The proportion of outpatient
      discharges was stable around 20% from 2007 to 2014 (range17-23%). The mean 90-day
      cost was lower for outpatients ($39,528 v. $47,330) but reimbursement fell nearly
      1/3 from 2007-2014 for both groups, and the difference between the two narrowed
      over time ($13,745 difference in 2008, to $3,834 in 2014). Outpatients had a
      lower incidence of overall 30-day complications (9.5% v. 18.6%, p<0.0001), but
      were also significantly less comorbid (mean Charlson comorbidity index 2.32 v.
      3.85, p<0.001). Older patient age, obesity, cardiac, renal, and pulmonary
      comorbidity were each more common in the inpatients (p<0.05 for each).
      Conclusions: Outpatient discharge after ACDF is a viable treatment option with a
      reasonable safety profile and decreased costs relative to inpatient admission.
      Appropriate patient selection is key, and the standard of care nationally for the
      comorbid patient remains inpatient admission. The economic trends and
      epidemiologic data presented here should be useful for health policy decisions.

PMID- 30104942
TI  - Long-Term Functional Outcomes of Distal Femoral Replacements Compared to
      Geographic Resections for Parosteal Osteosarcomas of the Distal Femur.
AB  - Background: Parosteal osteosarcoma is a rare tumor with increased survival
      compared to conventional high-grade osteosarcoma. Due to this increased survival
      comes the need for reconstructive options that provide good long-term functional
      results. Current treatment methods include geographic resection with allograft
      reconstruction versus resection and reconstruction with a distal femoral
      replacement. Purpose: Our purpose was to compare the long-term functional
      outcomes of distal femoral replacements to allograft reconstructions, using the
      musculoskeletal tumor society (MSTS) scoring system. Methods: After querying our
      database, 12 patients were identified and completed a MSTS questionnaire.
      Results: There was no difference in functional outcomes between the cohorts at an
      average of 14 years follow up for the endoprosthetic group and 25 years of follow
      up for the geographic resection group. Conclusion: At long-term follow-up,
      patients who undergo a distal femoral replacement for a parosteal osteosarcoma
      have no difference in functional outcomes compared to those who undergo an
      allograft reconstruction.Level of Evidence: IV.

PMID- 30104943
TI  - Systemic Lupus Erythematosus is a Risk Factor for Complications in Total Joint
      Arthroplasty.
AB  - Introduction: Systemic Lupus Erythematosus (SLE) has been associated with
      increased complications following hip and knee arthroplasty. The Purpose of this
      study was to determine the extent to which SLE is a risk factor in outcomes
      following total joint arthroplasty (TJA). Methods: The nationwide inpatient
      sample was used to identify a cohort of 505,841 patients who had a total hip
      arthroplasty (THA) or total knee arthroplasty (TKA) between 2009-2011. Of these
      patients, 2,284 patients (0.45%) had been previously diagnosed with SLE. The
      impact of SLE on short-term TJA outcomes was determined using multivariate
      logistic regression. Differences in discharge destination and length of stay were
      also evaluated. Results: SLE patients were more likely to have an all-cause
      medical complication, (OR 1.9, p<0.0001) and more likely to have an all-cause
      surgical complication (OR 1.3, p<0.0001). SLE patients were four times more
      likely to become septic in the post-operative period (OR 3.8, p<0.0487). SLE
      patients were more likely to have a genitourinary complication (OR 1.7, p<0.0001)
      and bleeding complications requiring transfusion (OR 2.1, p<0.0001). Patients
      with SLE also had an increased length of stay (0.38 days, p<0.0001) and increased
      probability of discharging to a facility (OR 2.1, p<0.0001). Discussion: Patients
      with SLE had an increased rate of both medical and surgical all-cause
      complications. Patients were specifically found to be at higher risk for sepsis,
      genitourinary complications, and blood transfusions. Future risk adjustment
      models should include SLE as a contributor to medical and surgical complications
      in the postoperative period.

PMID- 30104944
TI  - Total Hip Arthroplasty for Crowe Type IV Developmental Dysplasia of the Hip Using
      a Titanium Mesh Cup and Subtrochanteric Femoral Osteotomy.
AB  - Background: Treatment of Crowe IV developmental dysplasia of the hip (DDH) with
      total hip arthroplasty (THA) reconstructs the true acetabulum, which improves hip
      biomechanics and function. However, restoration of the native acetabulum may lead
      to limb lengthening and traction neuropraxia. The purpose of this study is to
      describe the short term results of a retrospectively reviewed series of patients
      with Crowe IV DDH treated with THA using a titanium mesh cup, cemented liner, and
      subtrochanteric femoral shortening osteotomy. Methods: Eighteen patients (21
      hips) with an average age of 47 years (age range: 28-61 years) with Crowe IV DDH
      underwent reconstructive THA and subtrochanteric femoral shortening osteotomy
      between September 2005 and February 2014. Follow up was assessed at 1, 3, 6, 9,
      and 12 months post operatively and then annually after the first year. The
      average follow up was 3.5 years (range 0.5-9 years). At each follow up visit,
      radiographs were used to assess for osteolysis and subsidence. Preoperative and
      postoperative patient reported outcomes including Harris Hip Score and Modified
      Merle d'Aubigne Hip Score were compared. Results: At the minimum 6 month follow
      up, all radiographic assessments showed no signs of osteolysis or subsidence of
      the implants. Both the Harris Hip Score and Modified Merle d'Aubigne Hip Score
      improved from preoperative assessments (p<0.05). Three patients developed
      symptoms of sciatic nerve neuropraxia that subsequently resolved. Conclusion: THA
      of Crowe IV DDH by reconstructing the acetabulum with bone graft, a titanium mesh
      cup, cemented liner, and subtrochanteric femoral shortening osteotomy
      demonstrated no osteolysis or subsidence and improved function with a low
      incidence of sciatic nerve palsy at short term follow up.Level of evidence: IV.

PMID- 30104945
TI  - Primary Total Hip Arthroplasty for Legg-Calve-Perthes Syndrome: 20 Year Follow-Up
      Study.
AB  - Background: Patients with Legg-Calve-Perthes Syndrome (LCPS) are at an increased
      risk for developing osteoarthritis of the hip and undergoing total hip
      arthroplasty (THA) at an early age. Importantly, this younger age may put them at
      a higher risk for failure and revision surgery. The purpose of the study was to
      assess the clinical and radiographic outcomes as well as implant failure rate and
      risk for revision surgery at an average 20 years follow up. Methods: Data from
      LCPS patients treated with THA were collected including age, gender, operative
      date, revision date, as well as reason for and type of revision. Living patients
      filled the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)
      questionnaires at the time of last follow-up. Radiographs were evaluated for
      lucencies, debonding, loosening, osteolysis, wear, heterotopic ossification and
      sclerosis. Results: Nineteen patients (20 hips) treated with THA were followed-up
      for a mean of 18.3 years (range, 10.1 - 36.2 years). Radiographic evidence of
      lucency of the acetabular component was seen in 70% of the patients and femoral
      cortical hypertrophy in 85% at last follow-up. The rate of revision for any
      reason was 35%, mostly due to aseptic acetabular loosening. Conclusions: Our
      findings support the use of THA for the treatment of OA in patients with LCPS,
      bearing in mind the potentially lower survival rate at 20 years as compared those
      treated with THA for primary OA. Further studies are needed to identify the
      possible causes of the high rate of cortical hypertrophy seen in this patient
      population.Level of Evidence: IV Therapeutic.

PMID- 30104947
TI  - 2018 IOJ Editors' Note.

PMID- 30104946
TI  - Might Doctors Really "Know Best"?: Utilizing Surgeon Intuition to Strengthen
      Preoperative Surgical Risk Assessment.
AB  - Background: Many clinical factors are known to increase an individual patient's
      risk of perioperative complications and hospital readmission. Several novel risk
      calculators have been created to predict the risk of postoperative complications
      for specific procedures that rely entirely on objective measurements. Our goal
      was to determine if surgeon intuition (an estimate of the percent likelihood of
      minor and major medical and surgical complications and 30-day readmission) could
      provide an additional source of data in the preoperative setting that may enhance
      the prediction of complications after surgery. Methods: We targeted the operative
      practices of three subspecialized orthopedic surgeons over a 6-month period
      (February 1 to July 31, 2015). We administered surveys to attending surgeons and
      assisting residents or nurse practitioners prior to each operation. Surgeons were
      asked to predict each patient's likelihood, on a scale from <1-100, for
      experiencing a complication. Following the procedure, we analyzed each patient's
      electronic medical record to determine any adverse events and readmissions. We
      then looked at levels of association between predictor variables and
      complications. Analysis of maximum likelihood estimates for complication outcome
      was performed comparing objective variables and surgeon prediction. Results: A
      total of 417 surveys in 270 patients were available for analysis. Defining the
      predicted likelihood of minor medical complications as <10% (low), 10-40%
      (intermediate), and >40% (high), provided discrimination of postoperative
      complications for a single observer in the first three month. These cutoff ranges
      showed inter-observer consistency and a trend towards intra-observer consistency.
      The only three variables predictive of minor medical complications were ASA class
      (OR=3.63, 95%CI=1.76-7.52, p=0.0005; comparing >2 vs <=2), age (beta=0.034+/
      0.012, p=0.0032) and surgeon prediction when comparing high to low risk
      (beta=0.034+/-0.008 (0.018-0.049), p<0.0001). Conclusions: Quantitative surgeon
      preoperative risk assessment was able to accurately discriminate between low- and
      high-risk groups of minor medical complications. We did not find a similar
      association between major complications and readmissions.Level of Evidence: IV.

PMID- 30104949
TI  - 2018 Dedication of the Iowa Orthopedic Journal: Dr. Charles R. Clark.

PMID- 30104950
TI  - 2018 Graduating Orthopedic Residents.

PMID- 30104951
TI  - 2018 Graduating Fellows.

PMID- 30104952
TI  - New Orthopedic Faculty.

PMID- 30104953
TI  - The 2018 Michael Bonfiglio Award for Student Research in Orthopaedic Surgery: The
      2018 Iowa Orthopaedic Society Medical Student Research Award for Musculoskeletal
      Research.

PMID- 30104954
TI  - Untargeted metabolomics analysis of ischemia-reperfusion-injured hearts ex vivo
      from sedentary and exercise-trained rats.
AB  - Introduction: The effects of exercise on the heart and its resistance to disease
      are well-documented. Recent studies have identified that exercise-induced
      resistance to arrhythmia is due to the preservation of mitochondrial membrane
      potential. Objectives: To identify novel metabolic changes that occur parallel to
      these mitochondrial alterations, we performed non-targeted metabolomics analysis
      on hearts from sedentary and exercise-trained rats challenged with isolated heart
      ischemia-reperfusion injury (I/R). Methods: Eight-week old Sprague-Dawley rats
      were treadmill trained 5 days/week for 6 weeks (exercise duration and intensity
      progressively increased to 1 h at 30 m/min up a 10.5% incline, 75-80% VO2max).
      The recovery of pre-ischemic function for sedentary rat hearts was 28.8 +/- 5.4%
      (N = 12) compared to exercise trained hearts, which recovered 51.9% +/- 5.7 (N =
      14) (p < 0.001). Results: Non-targeted GC-MS metabolomics analysis of (1)
      sedentary rat hearts; (2) exercise-trained rat hearts; (3) sedentary rat hearts
      challenged with global ischemia-reperfusion (I/R) injury; and (4) exercise
      trained rat hearts challenged with global I/R (10/group) revealed 15
      statistically significant metabolites between groups by ANOVA using Metaboanalyst
      (p < 0.001). Enrichment analysis of these metabolites for pathway-associated
      metabolic sets indicated a > 10-fold enrichment for ammonia recycling and protein
      biosynthesis. Subsequent comparison of the sedentary hearts post-I/R and exercise
      trained hearts post-I/R further identified significant differences in three
      metabolites (oleic acid, pantothenic acid, and campesterol) related to
      pantothenate and CoA biosynthesis (p <= 1.24E-05, FDR <= 5.07E-4). Conclusions:
      These studies shed light on novel mechanisms in which exercise-induced
      cardioprotection occurs in I/R that complement both the mitochondrial
      stabilization and antioxidant mechanisms recently described. These findings also
      link protein synthesis and protein degradation (protein quality control
      mechanisms) with exercise-linked cardioprotection and mitochondrial
      susceptibility for the first time in cardiac I/R.

PMID- 30104955
TI  - Dcf1 Deficiency Attenuates the Role of Activated Microglia During
      Neuroinflammation.
AB  - Microglia serve as the principal immune cells and play crucial roles in the
      central nervous system, responding to neuroinflammation via migration and the
      execution of phagocytosis. Dendritic cell-derived factor 1 (Dcf1) is known to
      play an important role in neural stem cell differentiation, glioma apoptosis,
      dendritic spine formation, and Alzheimer's disease (AD), nevertheless, the
      involvement of the Dcf1 gene in the brain immune response has not yet been
      reported. In the present paper, the RNA-sequencing and function enrichment
      analysis suggested that the majority of the down-regulated genes in Dcf1-/- (Dcf1
      KO) mice are immune-related. In vivo experiments showed that Dcf1 deletion
      produced profound effects on microglial function, increased the expression of
      microglial activation markers, such as ionized calcium binding adaptor molecule 1
      (Iba1), Cluster of Differentiation 68 (CD68) and translocator protein (TSPO), as
      well as certain proinflammatory cytokines (Cxcl1, Ccl7, and IL17D), but decreased
      the migratory and phagocytic abilities of microglial cells, and reduced the
      expression levels of some other proinflammatory cytokines (Cox-2, IL-1beta, IL-6,
      TNF-alpha, and Csf1) in the mouse hippocampus. Furthermore, in vitro experiments
      revealed that in the absence of lipopolysaccharide (LPS), the majority of
      microglia were ramified and existed in a resting state, with only approximately
      10% of cells exhibiting an amoeboid-like morphology, indicative of an activated
      state. LPS treatment dramatically increased the ratio of activated to resting
      cells, and Dcf1 downregulation further increased this ratio. These data indicated
      that Dcf1 deletion mediates neuroinflammation and induces dysfunction of
      activated microglia, preventing migration and the execution of phagocytosis.
      These findings support further investigation into the biological mechanisms
      underlying microglia-related neuroinflammatory diseases, and the role of Dcf1 in
      the immune response.

PMID- 30104957
TI  - Activation of Protein Kinase G After Repeated Cocaine Administration Is Necessary
      for the Phosphorylation of alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionic
      Acid Receptor GluA1 at Serine 831 in the Rat Nucleus Accumbens.
AB  - Phosphorylation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      (AMPA) receptors in the striatum plays a crucial role in regulating the receptor
      coupled signaling cascades leading to behavioral changes associated with
      psychostimulant exposure. The present study determined if activation of protein
      kinase G (PKG) contributes to the phosphorylation of AMPA receptor GluA1 subunit
      at the position of serine 831 (GluA1-S831) in the rat nucleus accumbens (NAc)
      after repeated cocaine administration. The results demonstrated that repeated
      intraperitoneal (i.p.) injections of cocaine (20 mg/kg) once a day for seven
      consecutive days significantly increased the level of phosphorylated (p)GluA1
      S831. This increase was decreased by the intra-NAc infusion of either the cyclic
      guanosine monophosphate (cGMP) analog, Rp-8-Br-PET-cGMPS (5 nmol/1 MUL), or the
      PKG inhibitor, KT5823 (2 nmol/1 MUL). Repeated cocaine administration increased
      PKG binding activity to GluA1. This increase in GluA1-S831 phosphorylation after
      repeated cocaine administration was decreased by the intra-NAc infusion of the
      synthetic peptide (Tat-tagged interfering peptide (Tat-GluA1-i)), that interferes
      with the binding of PKG to GluA1. Intra-NAc infusion of the interfering peptide
      also reduced the repeated cocaine-induced increase in locomotor activity. These
      findings suggest that activated PKG, after repeated exposure to cocaine, binds to
      AMPA receptor GluA1 and is required for the phosphorylation of S831, contributing
      to behavioral changes.

PMID- 30104958
TI  - Fast Ca2+ Transients of Inner Hair Cells Arise Coupled and Uncoupled to Ca2+
      Waves of Inner Supporting Cells in the Developing Mouse Cochlea.
AB  - Before the onset of hearing, which occurs around postnatal day 12 (P12) in mice,
      inner hair cells (IHCs) of the immature cochlea generate sound-independent Ca2+
      action potentials (APs), which stimulate the auditory pathway and guide
      maturation of neuronal circuits. During these early postnatal days, intercellular
      propagating Ca2+ waves elicited by ATP-induced ATP release are found in inner
      supporting cells (ISCs). It is debated whether IHCs are able to fire Ca2+ APs
      independently or require a trigger by an ISC Ca2+ wave. To identify the Ca2+
      transients of IHCs underlying Ca2+ APs and to analyze their dependence on ISC
      Ca2+ waves, we performed fast Ca2+ imaging of Fluo-8 AM-loaded organs of Corti at
      P4/P5. Fast Ca2+ transients (fCaTs) generated by IHCs were simultaneously imaged
      with Ca2+ waves in ISCs. ISC Ca2+ waves frequently evoked bursts consisting of >5
      fCaTs in multiple adjacent IHCs. Although Ca2+ elevations of small amplitude
      appeared to be triggered by ISC Ca2+ waves in IHCs of Cav1.3 knockout mice we
      never observed fCaTs, indicating their requirement for Ca2+ influx through Cav1.3
      channels. The Ca2+ wave-triggered Ca2+ upstroke in wildtype IHCs occurred 0.52 +/
      0.27 s later than the rise of the Ca2+ signal in the adjacent ISCs. In
      comparison, superfusion of 1 MUM ATP elicited bursts of fCaTs in IHCs starting
      0.99 +/- 0.34 s prior to Ca2+ elevations in adjacent ISCs. PPADS irreversibly
      abolished Ca2+ waves in ISCs and reversibly reduced fCaTs in IHCs indicating
      differential involvement of P2 receptors. IHC and ISC Ca2+ signals were however
      unaltered in P2X2R/P2X3R double knockout or in P2X7R knockout mice. Together, our
      data revealed a fairly similar occurrence of fCaTs within a burst (56.5%)
      compared with 43.5% as isolated single fCaTs or in groups of 2-5 fCaTs
      (minibursts). We provide evidence that IHCs autonomously generate single fCaTs
      and minibursts whereas bursts synchronized between neighboring IHCs were mostly
      triggered by ISC Ca2+ waves. Neonatal IHCs thus spontaneously generate electrical
      and Ca2+ activity, which is enhanced and largely synchronized by activity of ISCs
      of Kolliker's organ indicating two sources of spontaneous activity in the
      developing auditory system.

PMID- 30104960
TI  - Mild Endoplasmic Reticulum Stress Protects Against Lipopolysaccharide-Induced
      Astrocytic Activation and Blood-Brain Barrier Hyperpermeability.
AB  - Recent research has revealed that uncontrolled chronic neuroinflammation is
      closely associated with diverse neurodegenerative diseases, by impairing blood
      brain barrier (BBB) function and astrocytic reaction. Endoplasmic reticulum (ER)
      stress is conventionally linked to the loss of neuronal structure and function
      and should be widely attenuated. This notion has been questioned by recent
      experimental studies, which have shown that non-harmful levels of ER stress had
      numerous beneficial roles against neurodegeneration, including neuroprotection
      and inhibition of cytokine production. Here, we investigated the mild ER stress
      based regulation of LPS-induced inflammatory responses in astrocytes. Primary
      astrocytes were exposed to tunicamycin (TM), a compound that activates ER stress,
      with or without the ER-stress inhibitor sodium 4-phenylbutyrate (4-PBA) before
      LPS treatment. Astrocytic activation, proinflammatory factor production, and the
      extent of ER stress were assessed. In addition, the effect of mild ER stress on
      astrocytes and BBB function was determined in vivo. Male Sprague-Dawley rats
      received intracerebroventricular injections of TM with or without intraperitoneal
      4-PBA before LPS administration. The levels of astrocytic activation and BBB
      permeability were measured after treatment. Our results showed that lower doses
      of TM resulted in a mild ER-stress response without inducing cytotoxicity and
      tissue toxicity. Non-toxic ER-stress preconditioning ameliorated LPS-induced
      overactivation and inflammatory responses in astrocytes. Moreover, pre-exposure
      to non-lethal doses of TM improved LPS-induced BBB impairment and cognitive
      ability dysfunction in rats. However, 4-PBA, reversed the protective effect of TM
      preconditioning in vitro and in vivo. We conclude that mild ER stress
      ("preconditioning") can alleviate LPS-induced astrocytic activation and BBB
      disruption. Our findings provide a better understanding for the regulatory role
      of ER stress in neuroinflammation and indicate that mild ER stress might have
      therapeutic value for the treatment of neurodegenerative diseases.

PMID- 30104959
TI  - Trilobatin Protects Against Oxidative Injury in Neuronal PC12 Cells Through
      Regulating Mitochondrial ROS Homeostasis Mediated by AMPK/Nrf2/Sirt3 Signaling
      Pathway.
AB  - Oxidative stress-induced neuronal cell damage is a crucial factor in the
      pathogenesis of mitochondria-associated neurological diseases. Therefore,
      elimination of overproduction of mitochondrial reactive oxygen species (mtROS)
      may be a potential strategy for prevention and treatment of neurological
      diseases. In the present study, the neuroprotective effects of trilobatin (TLB),
      a novel small molecule monomer derived from Lithocarpus polystachyus Rehd, and
      its underlying mechanisms were investigated in vitro using hydrogen peroxide
      (H2O2)-induced oxidative stress model in a neuron-like PC12 cell. The findings
      revealed that pre-treatment with TLB dramatically concentration-dependently
      suppressed H2O2-induced PC12 cells damage by enhancing cell viability, repressed
      reduction of mitochondrial membrane potential (MMP) and decreased mtROS
      overgeneration, thereby deferring cell apoptosis. Further study demonstrated that
      TLB not only increased the enzymatic activities of glutathione peroxidase (GPx),
      isocitrate dehydrogenase 2 (IDH2),superoxide dismutase 2 (SOD2) and deacetylation
      of SOD2, but also activated silent mating-type information regulation 2 homolog 3
      (Sirt3) within the mitochondria and thereby upregulating forkheadboxO3a (FoxO3a),
      which regulated mitochondrial DNA genes, then led to improving complex I activity
      and adenosine triphosphate (ATP) synthesis. What's more, TLB up-regulated p
      adenosine monophosphate-activated protein kinase (AMPK) level, the expression of
      peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC
      1alpha), and ERRalpha. Intriguingly, TLB failed to mitigate H2O2-induced PC12
      injury in the presence of the AMPK inhibitor (Compound C), indicating that the
      beneficial effects of TLB on the regulation of mtROS homeostasis were reliance on
      AMPK -Sirt3 signaling pathway. Moreover, TLB also facilitated nuclear factor
      erythroid 2-related factor 2 (Nrf2) and promoted antioxidant gene expression in
      turn, and knockdown of Nrf2 by siRNA dramatically reduced the neuroprotective
      effects of TLB. Notably, AMPK inhibitor abolished the activation of Nrf2 and
      Sirt3, whereas, knockdown of Nrf2 blocked the upregulation of Sirt3, but it did
      not affect p-AMPK level. In conclusion, our findings demonstrate that TLB
      protects against oxidative injury in neuronal PC12 cells through regulating mtROS
      homeostasis in the first time, which is, at least partly, mediated through the
      AMPK/Nrf2/Sirt3 signaling pathway.

PMID- 30104956
TI  - Physiological Roles and Therapeutic Potential of Ca2+ Activated Potassium
      Channels in the Nervous System.
AB  - Within the potassium ion channel family, calcium activated potassium (KCa)
      channels are unique in their ability to couple intracellular Ca2+ signals to
      membrane potential variations. KCa channels are diversely distributed throughout
      the central nervous system and play fundamental roles ranging from regulating
      neuronal excitability to controlling neurotransmitter release. The physiological
      versatility of KCa channels is enhanced by alternative splicing and co-assembly
      with auxiliary subunits, leading to fundamental differences in distribution,
      subunit composition and pharmacological profiles. Thus, understanding specific
      KCa channels' mechanisms in neuronal function is challenging. Based on their
      single channel conductance, KCa channels are divided into three subtypes: small
      (SK, 4-14 pS), intermediate (IK, 32-39 pS) and big potassium (BK, 200-300 pS)
      channels. This review describes the biophysical characteristics of these KCa
      channels, as well as their physiological roles and pathological implications. In
      addition, we also discuss the current pharmacological strategies and challenges
      to target KCa channels for the treatment of various neurological and psychiatric
      disorders.

PMID- 30104961
TI  - The Microtubule-Modulating Drug Epothilone D Alters Dendritic Spine Morphology in
      a Mouse Model of Mild Traumatic Brain Injury.
AB  - Microtubule dynamics underpin a plethora of roles involved in the intricate
      development, structure, function, and maintenance of the central nervous system.
      Within the injured brain, microtubules are vulnerable to misalignment and
      dissolution in neurons and have been implicated in injury-induced glial responses
      and adaptive neuroplasticity in the aftermath of injury. Unfortunately, there is
      a current lack of therapeutic options for treating traumatic brain injury (TBI).
      Thus, using a clinically relevant model of mild TBI, lateral fluid percussion
      injury (FPI) in adult male Thy1-YFPH mice, we investigated the potential
      therapeutic effects of the brain-penetrant microtubule-stabilizing agent,
      epothilone D. At 7 days following a single mild lateral FPI the ipsilateral
      hemisphere was characterized by mild astroglial activation and a stereotypical
      and widespread pattern of axonal damage in the internal and external capsule
      white matter tracts. These alterations occurred in the absence of other overt
      signs of trauma: there were no alterations in cortical thickness or in the number
      of cortical projection neurons, axons or dendrites expressing YFP. Interestingly,
      a single low dose of epothilone D administered immediately following FPI (and
      sham-operation) caused significant alterations in the dendritic spines of layer 5
      cortical projection neurons, while the astroglial response and axonal pathology
      were unaffected. Specifically, spine length was significantly decreased, whereas
      the density of mushroom spines was significantly increased following epothilone D
      treatment. Together, these findings have implications for the use of microtubule
      stabilizing agents in manipulating injury-induced synaptic plasticity and
      indicate that further study into the viability of microtubule stabilization as a
      therapeutic strategy in combating TBI is warranted.

PMID- 30104962
TI  - Maturation of GABAergic Transmission in Cerebellar Purkinje Cells Is Sex
      Dependent and Altered in the Valproate Model of Autism.
AB  - Brain development is accompanied by a shift in gamma-aminobutyric acid (GABA)
      response from depolarizing-excitatory to hyperpolarizing-inhibitory, due to a
      reduction of intracellular chloride concentration. This sequence is delayed in
      Autism Spectrum Disorders (ASD). We now report a similar alteration of this shift
      in the cerebellum, a structure implicated in ASD. Using single GABAA receptor
      channel recordings in cerebellar Purkinje cells (PCs), we found two conductance
      levels (18 and 10 pS), the former being dominant in newborns and the latter in
      young-adults. This conductance shift and the depolarizing/excitatory to
      hyperpolarizing/inhibitory GABA shift occurred 4 days later in females than
      males. Our data support a sex-dependent developmental shift of GABA conductance
      and chloride gradient, leading to different developmental timing in males and
      females. Because these developmental sequences are altered in ASD, this study
      further stresses the importance of developmental timing in pathological
      neurodevelopment.

PMID- 30104965
TI  - Editorial: The Insect Central Complex-From Sensory Coding to Directing Movement.

PMID- 30104963
TI  - Hyperactive Response of Direct Pathway Striatal Projection Neurons to L-dopa and
      D1 Agonism in Freely Moving Parkinsonian Mice.
AB  - Dopamine (DA) profoundly stimulates motor function as demonstrated by the
      hypokinetic motor symptoms in Parkinson's disease (PD) and by the hyperkinetic
      motor side effects during dopaminergic treatment of PD. Dopamine (DA) receptor
      bypassing, optogenetics- and chemogenetics-induced spike firing of striatal DA D1
      receptor (D1R)-expressing, direct pathway medium spiny neurons (dSPNs or dMSNs)
      promotes movements. However, the endogenous D1R-mediated effects, let alone those
      of DA replacement, on dSPN spike activity in freely-moving animals is not
      established. Here we show that using transcription factor Pitx3 null mutant
      (Pitx3Null) mice as a model for severe and consistent DA denervation in the
      dorsal striatum in Parkinson's disease, antidromically identified striatonigral
      neurons (D1R-expressing dSPNs) had a lower baseline spike firing rate than that
      in DA-intact normal mice, and these neurons increased their spike firing more
      strongly in Pitx3Null mice than in WT mice in response to injection of L-dopa or
      the D1R agonist, SKF81297; the increase in spike firing temporally coincided with
      the motor-stimulating effects of L-dopa and SKF81297. Taken together, these
      results provide the first evidence from freely moving animals that in
      parkinsonian striatum, identified behavior-promoting dSPNs become hyperactive
      upon the administration of L-dopa or a D1 agonist, likely contributing to the
      profound dopaminergic motor stimulation in parkinsonian animals and PD patients.

PMID- 30104964
TI  - Overlapping Distribution of Orexin and Endocannabinoid Receptors and Their
      Functional Interaction in the Brain of Adult Zebrafish.
AB  - Hypocretins/Orexins neuropeptides are known to regulate numerous physiological
      functions, such as energy homeostasis, food intake, sleep/wake cycle, arousal and
      wakefulness, in vertebrates. Previous studies on mice have revealed an intriguing
      orexins/endocannabinoids (ECs) signaling interaction at both structural and
      functional levels, with OX-A behaving as a strong enhancer of 2-arachydonoyl
      glycerol (2-AG) biosynthesis. In this study, we describe, for the first time in
      the brain of zebrafish, the anatomical distribution and co-expression of orexin
      (OX-2R) and endocannabinoid (CB1R) receptors, suggesting a functional
      interaction. The immunohistochemical colocalization of these receptors by
      confocal imaging in the dorsal and ventral telencephalon, suprachiasmatic nucleus
      (SC), thalamus, hypothalamus, preoptic area (PO) and cerebellum, is reported.
      Moreover, biochemical quantification of 2-AG levels by LC-MS supports the
      occurrence of OX-A-induced 2-AG biosynthesis in the zebrafish brain after 3 h of
      OX-A intraperitoneal (i.p.; 3 pmol/g) or intracerebroventricular (i.c.v.; 0.3
      pmol/g) injection. This effect is likely mediated by OX-2R as it is counteracted
      by i.p./i.c.v administration of OX-2R antagonist (SB334867, 10 pmol/g). This
      study provides compelling morphological and functional evidence of an OX-2R/CB1R
      signaling interaction in the brain of adult zebrafish, suggesting the use of this
      well-established vertebrate animal model for the study of complex and
      phylogenetically conserved physiological functions.

PMID- 30104967
TI  - Prefrontal Cortex Oxygenation Evoked by Convergence Load Under Conflicting
      Stimulus-to-Accommodation and Stimulus-to-Vergence Eye-Movements Measured by
      NIRS.
AB  - Purpose: To extend our knowledge of the functional linkages between visual
      fatigue and regional cerebral prefrontal cortex (PFC) oxygenation, we measured
      time related hemodynamic changes over the right dorsolateral prefrontal cortex
      (dlPFC) during convergence load under conflicting stimulus-to-accommodation and
      stimulus-to-vergence eye movements with and without concurrent mental load.
      Methods: Twenty healthy participants with a median age of 28 years (range: 18-44
      years) fixated upon a vertical bar presented separately to the left and right
      eyes, using polarized filters, during four counterbalanced 10-min periods: (i) no
      accommodation/vergence conflict (Control, Ctrl); (ii) added convergence load and
      accommodation/vergence conflict (Conv); (iii) added cognitive load only (Cog)
      and; (iv) a combination of added cognitive and convergence load and
      accommodation/vergence conflict (Cc). Viewing distance was 65 cm. Non-invasive
      measurements of hemodynamic activity over the dlPFC were quantified by functional
      near-infrared spectroscopy (fNIRS). During the two-convergence load conditions,
      the horizontal disparity of the two bars varied dynamically from no disparity to
      a disparity set 20% below the individual threshold for diplopia. Cognitive load
      was induced by the n-back-2 test which required the subject to memorize and
      recall the changing colors of the horizontal bars and decide when a given color
      was the same as that occurring two colors previously. fNIRS data were averaged
      over 10-s windows centered at 0, 2, 4, 6, 8, and 10 min of each task, subtracted
      from a 20-s baseline window immediately preceding the visual task, and then
      represented as changes in oxygenated hemoglobin (DeltaHbO2), deoxygenated
      hemoglobin (DeltaHHb) and total hemoglobin (DeltatHb). Results: Linear mixed
      model analyses showed that hemodynamic activity was systematically influenced by
      time (p < 0.001). The group-averaged time-related level of change across the
      viewing conditions did not differ when compared with one another (p > 0.05).
      Larger convergence eye-movement responses under conflicting stimulus-to
      accommodation, and stimulus-to-vergence over time, increased DeltaHbO2 and
      DeltatHb only in condition Cc and after 8 min of task time (p < 0.10 for min-6
      and min-8: p < 0.05 for min-10). Discussion: Collectively, our data suggest that
      HbO2, HHb, and tHb, recorded over the dlPFC with fNIRS, can be used to assay the
      degree to which supervisory oculomotor control processes are activated during
      visually deficient near work.

PMID- 30104968
TI  - In Standing, Corticospinal Excitability Is Proportional to COP Velocity Whereas
      M1 Excitability Is Participant-Specific.
AB  - Reductions in the base of support (BOS) make standing difficult and require
      adjustments in the neural control of sway. In healthy young adults, we determined
      the effects of reductions in mediolateral (ML) BOS on peroneus longus (PL) motor
      evoked potential (MEP), intracortical facilitation (ICF), short interval
      intracortical inhibition (SICI) and long interval intracortical inhibition (LICI)
      using transcranial magnetic stimulation (TMS). We also examined whether
      participant-specific neural excitability influences the responses to increasing
      standing difficulty. Repeated measures ANOVA revealed that with increasing
      standing difficulty MEP size increased, SICI decreased (both p < 0.05) and ICF
      trended to decrease (p = 0.07). LICI decreased only in a sub-set of participants,
      demonstrating atypical facilitation. Spearman's Rank Correlation showed a
      relationship of rho = 0.50 (p = 0.001) between MEP size and ML center of pressure
      (COP) velocity. Measures of M1 excitability did not correlate with COP velocity.
      LICI and ICF measured in the control task correlated with changes in LICI and
      ICF, i.e., the magnitude of response to increasing standing difficulty.
      Therefore, corticospinal excitability as measured by MEP size contributes to ML
      sway control while cortical facilitation and inhibition are likely involved in
      other aspects of sway control while standing. Additionally, neural excitability
      in standing is determined by an interaction between task difficulty and
      participant-specific neural excitability.

PMID- 30104966
TI  - Spatial Representations in the Human Brain.
AB  - While extensive research on the neurophysiology of spatial memory has been
      carried out in rodents, memory research in humans had traditionally focused on
      more abstract, language-based tasks. Recent studies have begun to address this
      gap using virtual navigation tasks in combination with electrophysiological
      recordings in humans. These studies suggest that the human medial temporal lobe
      (MTL) is equipped with a population of place and grid cells similar to that
      previously observed in the rodent brain. Furthermore, theta oscillations have
      been linked to spatial navigation and, more specifically, to the encoding and
      retrieval of spatial information. While some studies suggest a single
      navigational theta rhythm which is of lower frequency in humans than rodents,
      other studies advocate for the existence of two functionally distinct delta-theta
      frequency bands involved in both spatial and episodic memory. Despite the general
      consensus between rodent and human electrophysiology, behavioral work in humans
      does not unequivocally support the use of a metric Euclidean map for navigation.
      Formal models of navigational behavior, which specifically consider the spatial
      scale of the environment and complementary learning mechanisms, may help to
      better understand different navigational strategies and their neurophysiological
      mechanisms. Finally, the functional overlap of spatial and declarative memory in
      the MTL calls for a unified theory of MTL function. Such a theory will critically
      rely upon linking task-related phenomena at multiple temporal and spatial scales.
      Understanding how single cell responses relate to ongoing theta oscillations
      during both the encoding and retrieval of spatial and non-spatial associations
      appears to be key toward developing a more mechanistic understanding of memory
      processes in the MTL.

PMID- 30104969
TI  - Learning a Foreign Language: A Review on Recent Findings About Its Effect on the
      Enhancement of Cognitive Functions Among Healthy Older Individuals.
AB  - Currently, there is an increasing number of older population groups, especially
      in developed countries. This demographic trend, however, may cause serious
      problems, such as an increase in aging diseases, one of which is dementia whose
      main symptom consists in the decline of cognitive functioning. Although there has
      been ongoing pharmacological research on this neurological disorder, it has not
      brought satisfying results as far as its treatment is concerned. Therefore,
      governments all over the world are trying to develop alternative, non
      pharmacological strategies/activities, which could help to prevent this cognitive
      decline while this aging population is still healthy in order to reduce future
      economic and social burden. One of the non-pharmacological approaches, which may
      enhance cognitive abilities and protect against the decline in healthy older
      population, seems to be the learning of a foreign language. The purpose of this
      mini-review article is to discuss recent findings about the effect of foreign
      language learning on the enhancement of cognitive functions among healthy older
      individuals. The findings, divided into three research areas, show that the
      learning of a foreign language may generate a lot of benefits for older
      individuals, such as enhancement of cognitive functioning, their self-esteem,
      increased opportunities of socializing, or reduction of costs. However, as Ware
      et al. (2017) indicate, any intervention program on foreign language learning
      should be well thought of and tailored to the needs of older people in order to
      be effective and avoid accompanying factors, such as older people's anxiety or
      low self-confidence. Nevertheless, more empirical studies should be done in this
      area.

PMID- 30104970
TI  - Structural Properties of Synaptic Transmission and Temporal Dynamics at
      Excitatory Layer 5B Synapses in the Adult Rat Somatosensory Cortex.
AB  - Cortical computations rely on functionally diverse and highly dynamic synapses.
      How their structural composition affects synaptic transmission and plasticity and
      whether they support functional diversity remains rather unclear. Here, synaptic
      boutons on layer 5B (L5B) pyramidal neurons in the adult rat barrel cortex were
      investigated. Simultaneous patch-clamp recordings from synaptically connected L5B
      pyramidal neurons revealed great heterogeneity in amplitudes, coefficients of
      variation (CVs), and failures (F%) of EPSPs. Quantal analysis indicated
      multivesicular release as a likely source of this variability. Trains of EPSPs
      decayed with fast and slow time constants, presumably representing release from
      small readily releasable (RRP; 5.40 +/- 1.24 synaptic vesicles) and large
      recycling (RP; 74 +/- 21 synaptic vesicles) pools that were independent and
      highly variable at individual synaptic contacts (RRP range 1.2-12.8 synaptic
      vesicles; RP range 3.4-204 synaptic vesicles). Most presynaptic boutons (~85%)
      had a single, often perforated active zone (AZ) with a ~2 to 5-fold larger pre-
      (0.29 +/- 0.19 MUm2) and postsynaptic density (0.31 +/- 0.21 MUm2) when compared
      with even larger CNS synaptic boutons. They contained 200-3400 vesicles (mean
      ~800). At the AZ, ~4 and ~12 vesicles were located within a perimeter of 10 and
      20 nm, reflecting docked and readily releasable vesicles of a putative RRP.
      Vesicles (~160) at 60-200 nm constituting the structural estimate of the presumed
      RP were ~2-fold larger than our functional estimate of the RP although both with
      a high variability. The remaining constituted a presumed large resting pool.
      Multivariate analysis revealed two clusters of L5B synaptic boutons distinguished
      by the size of their resting pool. Our functional and ultrastructural analyses
      closely link stationary properties, temporal dynamics and endurance of synaptic
      transmission to vesicular content and distribution within the presynaptic boutons
      suggesting that functional diversity of L5B synapses is enhanced by their
      structural heterogeneity.

PMID- 30104971
TI  - Effects of Transcranial Direct Current Stimulation (tDCS) Over the Frontal Polar
      Area on Motor and Executive Functions in Parkinson's Disease; A Pilot Study.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder with motor and non-motor
      symptoms due to degeneration of dopaminergic neurons. The current pharmacological
      treatments induce complications associated with long-term use. However, current
      stimulation techniques for PD treatment, such as deep brain stimulation (DBS),
      are too invasive. In this context, non-invasive brain stimulation including
      transcranial direct current stimulation (tDCS) may be a safe and effective
      alternative treatment for PD. We previously reported that anodal tDCS over the
      frontal polar area (FPA) improved motor functions in heathy subjects. Therefore,
      in the present study, effects of tDCS over the FPA on motor and cognitive
      functions of PD patients were analyzed. Nine PD patients (3 men and 6 women)
      participated in this cross over study with three tDCS protocols; anodal, cathodal
      or sham tDCS over the FPA. Each tDCS protocol was applied for 1 week (5
      times/week). Before and after each protocol, motor and cognitive functions of the
      patients were assessed using Unified PD Rating Scale [UPDRS (part III: motor
      examination)], Fugl Meyer Assessment set (FMA), Simple Test for Evaluating hand
      Function (STEF) and Trail Making Test A (TMT-A). The results indicated that
      anodal stimulation significantly decreased scores of motor disability in UPDRS
      III compared with sham and cathodal stimulation, and significantly increased
      scores of motor functions in FMA compared with sham stimulation. Furthermore,
      anodal stimulation significantly decreased time to complete a motor task
      requiring high dexterity in STEF compared with those requiring low and medium
      levels of dexterity. In addition, anodal stimulation significantly decreased time
      to complete the TMT-A task, which requires executive functions, compared with
      sham stimulation. To the best of our knowledge, this is the first clinical
      research reporting that tDCS over the FPA successfully improved the motor and non
      motor functions in PD patients. These findings suggest that tDCS over the FPA
      might be a useful alternative for the treatment of PD patients.

PMID- 30104973
TI  - Quantitative Evaluation of in Vivo Target Efficacy of Anti-tumor Agents via an
      Immunofluorescence and EdU Labeling Strategy.
AB  - Current methods used to evaluate in vivo target efficacy of selected compound
      include western blot to semi-quantitatively analyze protein expression. However,
      problems arise as it is difficult to compare in vivo target efficacy of anti
      tumor agents with the same mode of action. It is therefore desirable to develop a
      protocol that can quantitatively display in vivo target efficacy while also
      providing other useful information. In this study EdU labeling was used to mark
      out the proliferating area. The tumor tissue was accordingly divided into
      proliferating and non-proliferating areas. Fifteen tumor related proteins were
      stained by immunofluorescence and were found to express in either the
      proliferating or non-proliferating areas. This allows the quantitative analysis
      of protein expressions within the precise area. With simple image analysis, our
      method gave precise percent changes of protein expression and cell proliferation
      between the drugs treated group and the control group. Additional information,
      such as, the status of protein expression can also be obtained. This method
      exhibits high sensitivity, and provides a quantitative approach for in vivo
      evaluation of target efficacy.

PMID- 30104972
TI  - In vitro and in vivo Assessment of Keratose as a Novel Excipient of Paclitaxel
      Coated Balloons.
AB  - Purpose: Drug coated balloons (DCB) are continually improving due to advances in
      coating techniques and more effective excipients. Paclitaxel, the current drug
      choice of DCB, is a microtubule-stabilizing chemotherapeutic agent that inhibits
      smooth muscle cell proliferation. Excipients work to promote coating stability
      and facilitate paclitaxel transfer and retention at the target lesion, although
      current excipients lack sustained, long-term paclitaxel retention. Keratose, a
      naturally derived protein, has exhibited unique properties allowing for tuned
      release of various therapeutic agents. However, little is known regarding its
      ability to support delivery of anti-proliferative agents such as paclitaxel. The
      goal of this project was to thus demonstrate the feasibility of keratose as a DCB
      coating excipient to promote the release and delivery of paclitaxel. Methods:
      Keratose was combined with paclitaxel in vitro and the release kinetics of
      paclitaxel and keratose were evaluated through high performance liquid
      chromatograph-mass spectroscopy (HPLC-MS) and spectrophotometry, respectively. A
      custom coating method was developed to deposit keratose and paclitaxel on
      commercially available angioplasty balloons via an air spraying method. Coatings
      were then visualized under scanning electron microscopy and drug load quantified
      by HPLC-MS. Acute arterial transfer of paclitaxel at 1 h was assessed using a
      novel ex vivo model and further evaluated in vivo in a porcine ilio-femoral
      injury model. Results: Keratose demonstrated tunable release of paclitaxel as a
      function of keratose concentration in vitro. DCB coated via air spraying yielded
      consistent drug loading of 4.0 +/- 0.70 MUg/mm2. Under scanning electron
      microscopy, the keratose-paclitaxel DCB showed uniform coverage with a
      consistent, textured appearance. The acute drug transfer of the keratose
      paclitaxel DCB was 43.60 +/- 14.8 ng/mg at 1 h ex vivo. These measurements were
      further confirmed in vivo as the acute 1 h arterial paclitaxel levels were 56.60
      +/- 66.4 ng/mg. Conclusion: The keratose-paclitaxel coated DCB exhibited
      paclitaxel uptake and achieved acute therapeutic arterial tissue levels,
      confirming the feasibility of keratose as a novel excipient for DCB.

PMID- 30104974
TI  - Gambogic Acid and Its Analogs Inhibit Gap Junctional Intercellular Communication.
AB  - Gap junctions (GJs) are intercellular channels composed of connexins. Cellular
      molecules smaller than 1 kDa can diffuse through GJs by a process termed gap
      junctional intercellular communication (GJIC), which plays essential roles in
      various pathological and physiological conditions. Gambogic acid (GA), a major
      component of a natural yellow dye, has been used as traditional medicine and has
      been reported to have various therapeutic effects, including an anti-cancer
      effect. In this study, two different GJ assay methods showed that GA and its
      analogs inhibited GJIC. The inhibition was rapidly reversible and was not
      mediated by changes in surface expression or S368 phosphorylation of Cx43,
      cellular calcium concentration, or redox state. We also developed an assay system
      to measure the intercellular communication induced by Cx40, Cx30, and Cx43.
      Dihydrogambogic acid (D-GA) potently inhibited GJIC by Cx40 (IC50 = 5.1 MUM),
      whereas the IC50 value of carbenoxolone, which is known as a broad spectrum GJIC
      inhibitor, was 105.2 MUM. Thus, D-GA can act as a pharmacological tool for the
      inhibition of Cx40.

PMID- 30104976
TI  - Qiang-Xin 1 Formula Prevents Sepsis-Induced Apoptosis in Murine Cardiomyocytes by
      Suppressing Endoplasmic Reticulum- and Mitochondria-Associated Pathways.
AB  - Sepsis is reported to be an unusual systemic reaction to infection, accompanied
      by multiple-organ failure. Sepsis-induced cardiomyopathy (SIC), defined as
      damages and dysfunction of the heart, is essential in the pathogenesis of sepsis.
      Traditional Chinese formula, which has long been used to improve the situation of
      patients through multitarget regulation, is now gradually being used as
      complementary therapy. The present study aimed to investigate the effect of Qiang
      Xin 1 (QX1) formula, a traditional Chinese herbal medicine designed for cardiac
      dysfunction, on cecal ligation puncture (CLP)-induced heart damage and its
      underlying mechanisms in mice. Survival test first showed that an oral
      administration of QX1 formula significantly increased the 7-days survival of
      septic mice from 22 to 40%. By estimating the secretion of serum cytokines, QX1
      treatment dramatically inhibited the excessive production of interleukin-1beta
      and tumor necrosis factor-alpha. Immunohistochemical staining illustrated that
      the expression of c-Jun N-terminal kinase, caspase-12, and high-mobility group
      box 1 was downregulated in cardiomyocytes of the QX1-treated group compared with
      that of the CLP surgery group. Western blotting confirmed that the activation of
      essential caspase family members, such as caspase-3, caspase-9, and caspase-12,
      was prohibited by treatment with QX1. Moreover, the abnormal expression of key
      regulators of endoplasmic reticulum (ER) and mitochondria-associated apoptosis in
      cardiomyocytes of septic mice, including CHOP, GRP78, Cyt-c, Bcl-2, Bcl-XL, and
      Bax, was effectively reversed by treatment with QX1 formula. This study provided
      a new insight into the role of QX1 formula in heart damage and potential
      complementary therapeutic effect of traditional Chinese medicine on sepsis.

PMID- 30104975
TI  - In vivo Non-invasive Imaging of Radio-Labeled Exosome-Mimetics Derived From Red
      Blood Cells in Mice.
AB  - Exosomes are natural nano-sized membrane vesicles that have garnered recent
      interest owing to their potential as drug delivery vehicles. Though exosomes are
      effective drug carriers, their production and in vivo biodistribution are still
      not completely elucidated. We analyzed the production of exosome mimetics (EMs)
      from red blood cells (RBCs) and the radio-labeling of the RBC-EMs for in vivo
      imaging. Engineered EMs from RBCs were produced in large-scale by a one-step
      extrusion method, and further purified by density-gradient centrifugation. RBC
      EMs were labeled with technetium-99m (99mTc). For non-invasive imaging, 99mTc
      (free) or 99mTc-RBC-EMs were injected in mice, and their biodistribution was
      analyzed by gamma camera imaging. Animals were sacrificed, and organs were
      collected for further biodistribution analysis. RBC-EMs have similar
      characteristics as the RBC exosomes but have a 130-fold higher production yield
      in terms of particle numbers. Radiochemical purity of 99mTc-RBC-EMs was almost
      100% till 2 h reduced to 97% at 3 h. Radio-labeling did not affect the size and
      morphology of RBC-EMs. In contrast to free 99mTc, in vivo imaging of 99mTc-RBC
      EMs in mice showed higher uptake in the liver and spleen, and no uptake in the
      thyroid. Ex vivo imaging confirmed the in vivo findings. Furthermore, fluorescent
      imaging confirmed the nuclear imaging findings. Immunofluorescent imaging
      revealed that the hepatic uptake of RBC-EMs was significantly mediated by kupffer
      cells (resident hepatic macrophages). Our results demonstrate a simple yet large
      scale production method for a novel type of RBC-EMs, which can be effectively
      labeled with 99mTc, and feasibly monitored in vivo by nuclear imaging. The RBC
      EMs may be used as in vivo drug delivery vehicles.

PMID- 30104979
TI  - Editorial: Coenzyme Q Redox State and Cellular Homeostasis.

PMID- 30104977
TI  - Spinacetin Suppresses the Mast Cell Activation and Passive Cutaneous Anaphylaxis
      in Mouse Model.
AB  - We previously reported the anti-inflammatory and anti-asthmatic activities of the
      extract of the Inula japonica Thunb. Aiming for discovery of a novel anti
      inflammatory compound, we isolated spinacetin from the extract and investigated
      its in vitro and in vivo anti-inflammatory effect and the related mechanism.
      Effect of spinacetin on the Syk signaling pathway was studied in bone marrow
      derived mast cells (BMMCs), and that on the nuclear factor-kappaB (NF-kappaB) and
      mitogen-activated protein kinases (MAPKs) was investigated in Rat basophilic
      leukemia (RBL)-2H3 cells and human mast cell line (HMC-1). The in vivo anti
      inflammatory activity was assessed with passive cutaneous anaphylaxis (PCA)
      reaction assay. Spinacetin significantly inhibited the release of histamine, and
      production of inflammatory mediators such as leukotriene C4 (LTC4) and interlukin
      6 (IL-6) in IgE/Ag stimulated BMMCs. Analysis of the signaling pathways
      demonstrated that spinacetin inhibited activation of Syk, linker of activated T
      cells (LAT), phospholipase Cgamma (PLCgamma), cytosolic phospholipase A2 (cPLA2),
      MAPKs, Akt/NF-kappaB, and intracellular Ca2+ mobilization but with no effect on
      Fyn and Lyn. On the other hand, spinacetin suppressed IgE/Ag-induced activation
      of RBL-2H3 cells with inhibition against phosphorylation of extracellular signal
      regulated-protein kinase (ERK), c-Jun-NH2-terminal kinase (JNK), p38 MAPKs,
      PLCgamma, translocation of cPLA2, and Akt/IkappaBalpha/NF-kappaB signal. However,
      spinacetin had no effect on PMA and A23187-induced activation of HMC-1.
      Furthermore, oral administration of spinacetin dose-dependently attenuated IgE/Ag
      mediated PCA reaction in mouse model. Taken together, spinacetin showed the
      activities in preventing inflammatory processes, which might be at least
      partially attributed to the abolishment of Syk-dependent activation of IgE/Ag
      mediated mast cells.

PMID- 30104978
TI  - N-Terminal Extension and C-Terminal Domains Are Required for ABCB6/HMT-1 Protein
      Interactions, Function in Cadmium Detoxification, and Localization to the
      Endosomal-Recycling System in Caenorhabditis elegans.
AB  - The chronic exposure of humans to toxic metals such as cadmium from food and air
      causes dysfunction of vital organs, neurodegenerative conditions, and cancer. In
      this regard, members of the ABCB sub-family of the ATP-binding cassette (ABC)
      transporter superfamily, ABCB6/HMT-1, are acutely required for the detoxification
      of heavy metals and are present in genomes of many organisms including the
      nematode worm, Caenorhabditis elegans and humans. We showed previously that C.
      elegans ABCB6/HMT-1 detoxifies cadmium, copper, and arsenic, and is expressed in
      liver-like cells, the coelomocytes, head neurons and intestinal cells, which are
      the cell types that are affected by heavy metal poisoning in humans. The
      subcellular localization of ABCB6/HMT-1 proteins is unclear. ABCB6/HMT-1 proteins
      have a distinguishing topology: in addition to one transmembrane domain and one
      nucleotide-binding domain, they possess a hydrophobic N-terminal extension (NTE)
      domain encompassing five to six transmembrane spans. The role of the NTE domain
      in the function of ABCB6/HMT-1 in the native organism remains to be investigated.
      We used a versatile, multicellular model system, C. elegans, to establish the
      subcellular localization of ABCB6/HMT-1 and refine its structure-function studies
      in the native organism. We show that ABCB6/HMT-1 localizes mainly to the apical
      recycling endosomes and, in part, to early and late endosomes of intestinal
      cells. We also show that ABCB6/HMT-1 lacking the NTE domain is mistargeted to the
      plasma membrane and is unable to confer cadmium resistance. Although the NTE
      domain is essential for ABCB6/HMT-1 interaction with itself, the absence of NTE
      does not fully prevent this interaction. As a result, ABCB6/HMT-1 lacking the NTE
      domain, and expressed in wild-type worms or co-expressed with the full-length
      polypeptide, inactivates and mistargets the full-length ABCB6/HMT-1. We also show
      that the 43 amino acid residue stretch at the COOH-terminus is required for the
      ABCB6/HMT-1 interaction with itself and cadmium detoxification function. These
      results suggest that both NTE and COOH-terminus must be present to allow the
      protein to interact with itself and confer cadmium resistance. Considering that
      ABCB6/HMT-1 proteins are highly conserved, this study advances our understanding
      of how these proteins function in cadmium resistance in different species.
      Furthermore, these studies uncover the role of the endosomal-recycling system in
      cadmium detoxification.

PMID- 30104980
TI  - Modeling Pulmonary Gas Exchange and Single-Exhalation Profiles of Carbon
      Monoxide.
AB  - Exhaled breath carbon monoxide (eCO) is a candidate biomarker for non-invasive
      assessment of oxidative stress and respiratory diseases. Standard end-tidal CO
      analysis, however, cannot distinguish, whether eCO reflects endogenous CO
      production, lung diffusion properties or exogenous sources, and is unable to
      resolve a potential airway contribution. Coupling real-time breath gas analysis
      to pulmonary gas exchange modeling holds promise to improve the diagnostic value
      of eCO. A trumpet model with axial diffusion (TMAD) is used to simulate the
      dynamics of CO gas exchange in the respiratory system and corresponding eCO
      concentrations for the first time. The mass balance equation is numerically
      solved employing a computationally inexpensive routine implementing the method of
      lines, which provides the distribution of CO in the respiratory tract during
      inhalation, breath-holding, and exhalation with 1 mm spatial and 0.01 s temporal
      resolution. Initial estimates of the main TMAD parameters, the maximum CO fluxes
      and diffusing capacities in alveoli and airways, are obtained using healthy
      population tissue, blood and anatomical data. To verify the model, mouth-exhaled
      expirograms from two healthy subjects, measured with a novel, home-built laser
      based CO sensor, are compared to single-exhalation profiles simulated using
      actual breath sampling data, such as exhalation flow rate (EFR) and volume. A
      very good agreement is obtained in exhalation phases I and III for EFRs between
      55 and 220 ml/s and after 10 and 20 s of breath-holding, yielding a unique set of
      TMAD parameters. The results confirm the recently observed EFR dependence of CO
      expirograms and suggest that measured end-tidal eCO is always lower than alveolar
      and capillary CO. Breath-holding allows the observation of close-to-alveolar CO
      concentrations and increases the sensitivity to the airway TMAD parameters in
      exhalation phase I. A parametric simulation study shows that a small increase in
      airway flux can be distinguished from an increase in alveolar flux, and that
      slight changes in alveolar flux and diffusing capacity have a significantly
      different effect on phase III of the eCO profiles.

PMID- 30104983
TI  - Editorial: Perivascular Adipose Tissue (PVAT) in Health and Disease.

PMID- 30104981
TI  - Hyperbaric Oxygen Increases Stem Cell Proliferation, Angiogenesis and Wound
      Healing Ability of WJ-MSCs in Diabetic Mice.
AB  - Hyperbaric oxygen therapy (HBOT) is effective for the medical treatment of
      diverse diseases, infections, and tissue injury. In fact, in recent years there
      is growing evidence on the beneficial effect of HBOT on non-healing ischemic
      wounds. However, there is still yet discussion on how this treatment could
      benefit from combination with regenerative medicine strategies. Here we analyzed
      the effects of HBOT on three specific aspects of tissue growth, maintenance, and
      regeneration: (i) modulation of adult rodent (Mus musculus) intestinal stem cell
      turnover rates; (ii) angiogenesis dynamics during the development of the chorio
      allantoic membrane (CAM) in Gallus gallus embryos; (iii) and wound-healing in a
      spontaneous type II diabetic mouse model with a low capacity to regenerate skin.
      To analyze these aspects of tissue growth, maintenance, and regeneration, we used
      HBOT alone or in combination with cellular therapy. Specifically, Wharton Jelly
      Mesenchymal Stem cells (WJ-MSC) were embedded in a commercial collagen-scaffold.
      HBOT did not affect the metabolic rate of adult mice nor of chicken embryos.
      Notwithstanding, HBOT modified the proliferation rate of stem cells in the mice
      small intestinal crypts, increased angiogenesis in the CAM, and improved wound
      healing and tissue repair in diabetic mice. Moreover, our study demonstrates that
      combining stem cell therapy and HBOT has a collaborative effect on wound-healing.
      In summary, our data underscore the importance of oxygen tension as a regulator
      of stem cell biology and support the potential use of oxygenation in clinical
      treatments.

PMID- 30104982
TI  - Effects of Hypoxia and Bed Rest on Markers of Cardiometabolic Risk: Compensatory
      Changes in Circulating TRAIL and Glutathione Redox Capacity.
AB  - In chronic diseases, hypoxia and physical inactivity are associated with
      atherosclerosis progression. In contrast, a lower mortality from coronary artery
      disease and stroke is observed in healthy humans residing at high altitude in
      hypoxic environments. Eleven young, male volunteers completed the following 10
      day campaigns in a randomized order: hypoxic ambulatory, hypoxic bed rest and
      normoxic bed rest. Before intervention, subjects were evaluated in normoxic
      ambulatory condition. Normobaric hypoxia was achieved in a hypoxic facility
      simulating 4000 m of altitude. Following hypoxia, either in bed rest or
      ambulatory condition, markers of cardiometabolic risk shifted toward a more
      atherogenic pattern consisting of: (a) lower levels of total HDL cholesterol and
      HDL2 sub-fraction and decreased hepatic lipase; (b) activation of systemic
      inflammation, as determined by C-reactive protein and serum amyloid A; (c)
      increased plasma homocysteine; (d) decreased delta-5 desaturase index in cell
      membrane fatty acids, a marker of insulin sensitivity. Bed rest and hypoxia
      additively decreased total HDL and delta-5 desaturase index. In parallel to the
      pro-atherogenic effects, hypoxia activated selected anti-atherogenic pathways,
      consisting of increased circulating TNF-related apoptosis-inducing ligand
      (TRAIL), a protective factor against atherosclerosis, membrane omega-3 index and
      erythrocyte glutathione availability. Hypoxia mediated changes in TRAIL
      concentrations and redox glutathione capacity (i.e., GSH/GSSG ratio) were greater
      in ambulatory conditions (+34 +/- 6% and +87 +/- 31%, respectively) than in bed
      rest (+17 +/- 7% and +2 +/- 27% respectively). Hypoxia-induced cardiometabolic
      risk is blunted by moderate level of physical activity as compared to bed rest.
      TRAIL and glutathione redox capacity may contribute to the positive interaction
      between physical activity and hypoxia. Highlights: - Hypoxia and bed rest
      activate metabolic and inflammatory markers of atherogenesis. - Hypoxia and
      physical activity activate selected anti-atherogenic pathways. - Hypoxia and
      physical activity positive interaction involves TRAIL and glutathione.

PMID- 30104985
TI  - Effects of 3D Contemplative Landscape Videos on Brain Activity in a Passive
      Exposure EEG Experiment.
AB  - Background: Studies on Contemplative Landscapes (CL) show that not only do they
      have high ecological and visual values and are preferred by a majority of people,
      but they also can be beneficial to our mental health and well-being. Physical
      attributes of CL have been studied and operationalized, which has led to the
      development of the psychometric measurement tool called the Contemplative
      Landscape Questionnaire (CLQ) (1). Objectives: In the present study, we applied
      an experimental approach to the analysis of CL. We hypothesized that, when
      compared to Non-Contemplative Landscapes (NCL), they would induce higher frontal
      alpha power asymmetry, higher temporal beta power asymmetry and lower bilateral
      frontal beta power. Methods: Thirty-two healthy individuals (12 female) took part
      in the study. During the experimental protocol, participants were asked to
      passively view 12 landscapes, six CL and six NCL, while continuous EEG was
      recorded in a within-subjects design. Results: We found significantly increased
      power in the beta frequency band of the right temporal brain regions in the
      viewings of CL compared to NCL Conclusions: The findings suggest that
      Contemplative Landscapes capture more visual, stimuli-driven attention from the
      viewers and can be linked with switching attention systems (described in
      Attention Restoration Theory), which is compatible with a stress reduction
      mechanism.

PMID- 30104986
TI  - Commentary: The Concept of a Bewusstseinskultur.

PMID- 30104984
TI  - Differences in Physiological Responses During Rowing and Cycle Ergometry in Elite
      Male Rowers.
AB  - Cycle training is an important training modality of elite rowers. Cycling is the
      preferred alternative to on-water and ergometer rowing as it provides a reduction
      in compressive forces on the thoracic cage and upper extremities while still
      creating a local and central acclimation to endurance training. It is
      hypothesised, however, that there will be differences in physiological
      characteristics between Concept II (CII) rowing and WattBike (WB) cycling due to
      the principle regarding the specificity of training that elite rowers undertake.
      Understanding these differences will ensure more accurate training prescription
      when cycling. Twenty international level male rowers, [ V O2PEAK 5.85 +/- 0.58
      L.min-1 (CI +/- 0.26 L.min-1)] participated in two identical discontinuous
      incremental exercise tests on a CII rowing and WB cycle ergometer. Ergometer
      modalities were randomised and counterbalanced among the group and tests occurred
      7 days apart. V O2, V CO2, VE(STPD) and HR were significantly higher for every
      submaximal power output on the CII compared with the WB. Maximal power output on
      the WB was higher than on the CII [42 +/- 33 W (CI +/- 14 W) p < 0.000] but V
      O2PEAK was similar between modalities. Minute ventilation at maximal exercise was
      11 L.min-1 lower on CII than on WB. When data were expressed relative to modality
      specific V O2PEAK, power output was consistently lower on the CII as was
      submaximal V CO2, RER, RPE, mechanical efficiency and BLa concentration at 75% V
      O2PEAK. Across all power outputs and exercise modalities, 77% of the variance in
      RPE could be explained by the variance in BLa. These results demonstrate that
      elite rowers can attain similar V O2PEAK scores regardless of modality.
      Substantial physiological and metabolic differences are evident between CII
      rowing and WB cycling when power output is the independent variable with the
      latter being over 40 W higher. The difference in displayed power output between
      the ergometer modalities is attributed to differences in mechanical efficiency
      and a degree of power output not being accounted for on the CII ergometer. Given
      the lack of consistency between CII and WB power output, other physiological
      measures, such as HR, are better suited to prescribe WB ergometer sessions.

PMID- 30104987
TI  - Intrinsic Motivation Mediates the Association Between Exercise-Associated Affect
      and Physical Activity Among Adolescents.
AB  - American adolescents overwhelmingly engage in insufficient physical activity
      (PA). Attention has turned to the role of affect in shaping PA, raising questions
      as to whether the impact of affect on PA is direct/automatic or cognitively
      mediated ("Type 1" or "Type 2" in the dual-process model). This study examines
      whether intrinsic motivation (IM) mediates the association between affect and PA.
      Adolescents (N = 142, 48% Male, 20% non-Latino White, mean age = 11.04 years,
      mean VO2 = 37.19 ml/kg/min, mean BMI = 63.19) completed assessments of
      cardiorespiratory fitness, affective response to exercise on a stationary cycle,
      IM, preferred exercise intensity, and moderate-to-vigorous PA (MVPA; ActiGraph).
      Fitness, exercise intensity and MVPA assessments were repeated 5 months later.
      Tests for mediation showed that affect predicted PA at baseline and 5 months, and
      IM mediated the relationship between affect and PA both cross-sectionally (CI =
      0.03, 0.17) and longitudinally (CI = 0.04, 0.18). Results suggest a cognitively
      mediated pathway from affect to behavior. Adolescent PA may be increased either
      by enhancing IM or by tailoring interventions to accommodate individuals with a
      predisposition to respond to exercise with negative affect. This study is
      registered with Clinicaltrials.gov (ID # NCT01876602).

PMID- 30104988
TI  - Failure to Find a Conditioned Placebo Analgesic Response.
AB  - Background: Associative learning has, in several studies, been modulated by the
      sex of the participant. Consistent with this, a recent review found that
      conditioned nocebo effects are stronger in females than in males. Purpose: It has
      been suggested that conditioned placebo responses are stronger in females, and
      this hypothesis was investigated in the present study. Cortisol and measures of
      negative emotions were taken to investigate if these processes could mediate any
      conditioned placebo effects. Methods: Cold pain was applied to the volar forearm.
      The Conditioned group received inert capsules prior to two presentations of less
      painful stimulations, to associate intake of the capsules with reduced pain. The
      pain control group received the same painful stimulation as the Conditioned
      group, but no capsules. The Capsule control group received the capsules in the
      same way as the Conditioned group, but no decrease in the painful stimulation.
      Participant sex was crossed across groups. It was hypothesized that in the
      Conditioned group, an expectation of reduced pain should be induced after
      administration of the capsules, and this should generate placebo analgesia, and
      mostly so in females. Results: The Conditioned group reported lower pain during
      conditioning, and rated the capsules as more effective painkillers than the
      capsule control group. However, placebo analgesia was not reliably observed in
      the Conditioned group. Conclusion: The placebo capsules were rated as effective
      painkillers, but this did not translate into a placebo analgesic effect. This
      could be due to violation of response expectancies, too few conditioning trials,
      and differences in pain ratings in the pre-test that could be due to previous
      experience with painkillers.

PMID- 30104989
TI  - Sound Categories: Category Formation and Evidence-Based Taxonomies.
AB  - Five evidence-based taxonomies of everyday sounds frequently reported in the
      soundscape literature have been generated. An online sorting and category
      labeling method that elicits rather than prescribes descriptive words was used. A
      total of N = 242 participants took part. The main categories of the soundscape
      taxonomy were people, nature, and manmade, with each dividing into further
      categories. Sounds within the nature and manmade categories, and two further
      individual sound sources, dogs, and engines, were explored further by repeating
      the procedure using multiple exemplars. By generating multidimensional spaces
      containing both sounds and the spontaneously generated descriptive words the
      procedure allows for the interpretation of the psychological dimensions along
      which sounds are organized. This reveals how category formation is based upon
      different cues - sound source-event identification, subjective-states, and
      explicit assessment of the acoustic signal - in different contexts. At higher
      levels of the taxonomy the majority of words described sound source-events. In
      contrast, when categorizing dog sounds a greater proportion of the words
      described subjective-states, and valence and arousal scores of these words
      correlated with their coordinates along the first two dimensions of the data.
      This is consistent with valence and arousal judgments being the primary
      categorization strategy used for dog sounds. In contrast, when categorizing
      engine sounds a greater proportion of the words explicitly described the acoustic
      signal. The coordinates of sounds along the first two dimensions were found to
      correlate with fluctuation strength and sharpness, consistent with explicit
      assessment of acoustic signal features underlying category formation for engine
      sounds. By eliciting descriptive words the method makes explicit the subjective
      meaning of these judgments based upon valence and arousal and acoustic
      properties, and the results demonstrate distinct strategies being spontaneously
      used to categorize different types of sounds.

PMID- 30104990
TI  - Editorial: What Is the Role for Effective Pedagogy in Contemporary Higher
      Education?

PMID- 30104991
TI  - Beyond Cognition: Experts' Views on Affective-Motivational Research Dispositions
      in the Social Sciences.
AB  - Research competence (RC) as a key ability of students in the social sciences has
      thus far been conceptualized as consisting primarily of cognitive dispositions.
      However, owing to its highly complex and demanding nature, competence in
      conducting research might require additional affective and motivational
      dispositions. To address this deficiency in the literature, first, we conducted a
      qualitative interview study with academic experts (N = 16) in which we asked them
      to identify challenging research situations and the affective-motivational
      research dispositions needed to cope with them. We employed a subsequent online
      rating (N = 27) to evaluate the situations and dispositions that had been
      identified. The resulting affective-motivational facet of RC encompasses six
      challenging situations that are often encountered and nine dispositions that are
      necessary to successfully conduct research in the social sciences and may be used
      to both inform and evaluate research-based learning. The interview-based approach
      may serve as an exemplary procedure to postulate affective-motivational facets of
      competence models.

PMID- 30104992
TI  - A Growth-Curve Analysis of the Effects of Future-Thought Priming on Insight and
      Analytical Problem-Solving.
AB  - Research based on construal level theory (CLT) suggests that thinking about the
      distant future can prime people to solve problems by insight (i.e., an "aha"
      moment) while thinking about the near future can prime them to solve problems
      analytically. In this study, we used a novel method to elucidate the time-course
      of temporal priming effects on creative problem solving. Specifically, we used
      growth-curve analysis (GCA) to examine the time-course of priming while
      participants solved a series of brief verbal problems. Participants were tested
      in two counterbalanced sessions in a within-subject experimental design; one
      session featured near-future priming and the other featured far-future priming.
      Our results suggest high-level construal may temporarily enhance analytical
      thinking; far-future priming caused transient facilitation of analytical solving
      while near-future priming induced weaker, transient facilitation of insightful
      solving. However, this effect is short-lived; priming produced no significant
      differences in the total number of insights and analytical solutions. Given the
      fleeting nature of these effects, future studies should consider implementing
      methodology that allows for aspects of the time-course of priming effects to be
      examined. A method such as GCA may reveal mild effects that would be otherwise
      missed using other types of analyses.

PMID- 30104993
TI  - Multiple Representations of Space by the Cockroach, Periplaneta americana.
AB  - When cockroaches are trained to a visual-olfactory cue pairing using the antennal
      projection response (APR), they can form different memories for the location of a
      visual cue. A series of experiments, each examining memory for the spatial
      location of a visual cue, were performed using restrained cockroaches. The first
      group of experiments involved training cockroaches to associate a visual cue (CS
      green LED) with an odor cue (US) in the presence or absence of a second visual
      reference cue (white LED). These experiments revealed that cockroaches have at
      least two forms of spatial memory. First, it was found that during learning, the
      movements of the antennae in response to the odor influenced the cockroaches'
      memory. If they use only one antenna, cockroaches form a memory that results in
      an APR being elicited to the CS irrespective of its location in space. When using
      both antennae, the cockroaches resulting memory leads to an APR to the CS that is
      spatially confined to within 15 degrees  of the trained position. This memory
      represents an egocentric spatial representation. Second, the cockroaches
      simultaneously formed a memory for the angular spatial relationships between two
      visual cues when trained in the presence of a second visual reference cue. This
      training provided the cockroaches an allocentric representation or visual
      snapshot of the environment. If both egocentric and the visual snapshot were
      available to the cockroach to localize the learned cue, the visual snapshot
      determined the behavioral response in this assay. Finally, the split-brain assay
      was used to characterize the cockroach's ability to establish a memory for the
      angular relationship between two visual cues with half a brain. Split-brain
      cockroaches were trained to unilaterally associate a pair of visual cues (CS
      green LED and reference-white LED) with an odor cue (US). Split-brain cockroaches
      learned the general arrangement of the visual cues (i.e., the green LED is right
      of the white LED), but not the precise angular relationship. These experiments
      provide new insight into spatial memory processes in the cockroach.

PMID- 30104994
TI  - Community-Dwelling People Living With Dementia and Their Family Caregivers
      Experience Enhanced Relationships and Feelings of Well-Being Following
      Therapeutic Group Singing: A Qualitative Thematic Analysis.
AB  - The progression of dementia can severely compromise interpersonal connection and
      relationship quality between people living with dementia (PwD) and their family
      caregivers (FCG), leading to social isolation and poor quality of life for both.
      Therapeutic group singing (TGS) is a socially engaging, stimulating, and
      supportive pursuit that community-dwelling PwD and their FCG can participate in
      together. This study aimed to build on the findings from previous research by
      undertaking a thematic analysis of interviews with nine PwD (five women, four
      men; mean age = 79.1 years) and nine FCG (five women, four men; mean age = 75.7
      years). The interviews explored participants' perspectives and experiences of a
      20-week TGS intervention, underpinned by Kitwood's model of person-centered care.
      Inductive thematic analysis resulted in the emergence of five themes which
      described how TGS for PwD and their FCG: (1) included supportive therapeutic
      facilitation and design features; (2) made group singing more accessible; (3)
      fostered new empathic friendships; (4) enhanced relationships between PwD and
      FCG; and (5) led to personal feelings of wellbeing for both PwD and FCG. Affinity
      with others who had similar life experiences and challenges created a sense of
      mutual understanding and camaraderie, which made group singing accessible without
      fear of judgment and social stigmas. For some PwD/FCG dyads, TGS meant they could
      continue a lifelong passion for singing together, while others enjoyed
      participating in singing together for the first time. Both PwD and FCG
      participants described personal feelings of acceptance, improved social
      confidence, mood, and purpose. Further, participants valued mental stimulation
      from TGS such as learning new skills and memory support. A model explaining
      relationships between themes suggests that TGS with person-centered facilitation
      features for PwD/FCG dyads led to affinity among group members with ripple
      effects, which enhanced accessibility to group singing, the formation of empathic
      friendships, PwD/FCG relationship quality, and personal wellbeing for both PwD
      and FCG. Psychoemotional, social and cognitive benefits from TGS described by
      participants in this study are known to promote self-identity, healthy
      relationships, and quality of life. This research highlights a need for improved
      availability of TGS for community-dwelling PwD/FCG dyads.

PMID- 30104995
TI  - The Role of Gamma Oscillations During Integration of Metaphoric Gestures and
      Abstract Speech.
AB  - Metaphoric (MP) co-speech gestures are commonly used during daily communication.
      They communicate about abstract information by referring to gestures that are
      clearly concrete (e.g., raising a hand for "the level of the football game is
      high"). To understand MP co-speech gestures, a multisensory integration at
      semantic level is necessary between abstract speech and concrete gestures. While
      semantic gesture-speech integration has been extensively investigated using
      functional magnetic resonance imaging, evidence from electroencephalography (EEG)
      is rare. In the current study, we set out an EEG experiment, investigating the
      processing of MP vs. iconic (IC) co-speech gestures in different contexts, to
      reveal the oscillatory signature of MP gesture integration. German participants
      (n = 20) viewed video clips with an actor performing both types of gestures,
      accompanied by either comprehensible German or incomprehensible Russian (R)
      speech, or speaking German sentences without any gestures. Time-frequency
      analysis of the EEG data showed that, when gestures were accompanied by
      comprehensible German speech, MP gestures elicited decreased gamma band power (50
      70 Hz) between 500 and 700 ms in the parietal electrodes when compared to IC
      gestures, and the source of this effect was localized to the right middle
      temporal gyrus. This difference is likely to reflect integration processes, as it
      was reduced in the R language and no-gesture conditions. Our findings provide the
      first empirical evidence suggesting the functional relationship between gamma
      band oscillations and higher-level semantic processes in a multisensory setting.

PMID- 30104996
TI  - Combinatory Biomarker Use of Cortical Thickness, MUNIX, and ALSFRS-R at Baseline
      and in Longitudinal Courses of Individual Patients With Amyotrophic Lateral
      Sclerosis.
AB  - Objective: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative
      process affecting upper and lower motor neurons as well as non-motor systems. In
      this study, precentral and postcentral cortical thinning detected by structural
      magnetic resonance imaging (MRI) were combined with clinical (ALS-specific
      functional rating scale revised, ALSFRS-R) and neurophysiological (motor unit
      number index, MUNIX) biomarkers in both cross-sectional and longitudinal
      analyses. Methods: The unicenter sample included 20 limb-onset classical ALS
      patients compared to 30 age-related healthy controls. ALS patients were treated
      with standard Riluzole and additional long-term G-CSF (Filgrastim) on a named
      patient basis after written informed consent. Combinatory biomarker use included
      cortical thickness of atlas-based dorsal and ventral subdivisions of the
      precentral and postcentral cortex, ALSFRS-R, and MUNIX for the musculus abductor
      digiti minimi (ADM) bilaterally. Individual cross-sectional analysis investigated
      individual cortical thinning in ALS patients compared to age-related healthy
      controls in the context of state of disease at initial MRI scan. Beyond
      correlation analysis of biomarkers at cross-sectional group level (n = 20),
      longitudinal monitoring in a subset of slow progressive ALS patients (n = 4)
      explored within-subject temporal dynamics of repeatedly assessed biomarkers in
      time courses over at least 18 months. Results: Cross-sectional analysis
      demonstrated individually variable states of cortical thinning, which was most
      pronounced in the ventral section of the precentral cortex. Correlations of
      ALSFRS-R with cortical thickness and MUNIX were detected. Individual longitudinal
      biomarker monitoring in four slow progressive ALS patients revealed evident
      differences in individual disease courses and temporal dynamics of the
      biomarkers. Conclusion: A combinatory use of structural MRI, neurophysiological
      and clinical biomarkers allows for an appropriate and detailed assessment of
      clinical state and course of disease of ALS.

PMID- 30104997
TI  - Levodopa-Carbidopa Intestinal Gel in Parkinson's Disease: A Systematic Review and
      Meta-Analysis.
AB  - Background: Levodopa has been widely used and regarded as the most effective
      therapy for Parkinson's disease (PD), but long-term treatment with oral levodopa
      may result in motor fluctuations and involuntary movements (dyskinesias). There
      is evidence to suggest that Continuous infusion of levodopa-carbidopa intestinal
      gel (LCIG) can effectively manage motor and non-motor complications in PD, but
      clinical studies investigating this have yielded inconsistent results. This
      systematic review and meta-analysis was performed to examine the efficacy and
      safety of LCIG for patients with PD. Methods: A systematic search was conducted
      to retrieve published data in the EMBASE, PubMed, and the Cochrane Library up to
      March 2018. Both efficiency and safety of LCIG were analyzed using pooled
      standardized mean differences (SMDs) or odds ratio (ORs) with 95% confidence
      interval (CIs). Results: Eight trials with 384 PD patients were included in the
      present study. Compared with the control group, LCIG significantly decreased off
      time (SMD, -1.19; 95% CI, -2.25 to -0.12; p = 0.003) and increased on-time
      without troublesome dyskinesia (SMD, 0.55; 95% CI, 0.20 to 0.90; p = 0.002).
      However, no significant difference of LCIG was found in on-time with troublesome
      dyskinesia. There were no significant differences in UPDRS, Hoehn & Yahr and PDQ
      39 scores. Besides, no significant differences in the drop-out and adverse
      effects. Conclusions: Continuous delivery of LCIG may offer a promising option
      for PD patients. More randomized double-blind controlled studies with large
      sample sizes were needed to further confirm the efficacy and safety of LCIG for
      PD patients.

PMID- 30104998
TI  - Visual Target Strategies in Infantile Nystagmus Patients With Horizontal Jerk
      Waveform.
AB  - The aim of this study was to propose a new pathophysiological hypothesis for
      involuntary eye oscillation in infantile nystagmus (IN): patients with IN exhibit
      impaired gaze fixation, horizontal smooth pursuit and optokinetic nystagmus (OKN)
      and use saccadic eye movements for these underlying impairments. In order to
      induce saccades, they make enough angle between gaze and target by precedent
      exponential slow eye movements. IN consists of the alternate appearance of the
      saccade and the slow eye movements. Unlike most previous theories, IN is
      therefore considered a necessary strategy allowing for better vision and not an
      obstacle to clear vision. In five patients with IN, eye movements were analyzed
      during the smooth pursuit test, saccadic eye movement test, OKN test and
      vestibulo-ocular reflex (VOR) test. Their gaze fixation, horizontal smooth
      pursuit, OKN and the last half of the slow phase of VOR were impaired. The lines
      obtained by connection of the end eye positions of fast phase of nystagmus
      coincided with the trajectories of targets. The findings indicate that patients
      followed the target by the fast but not the slow phase of nystagmus, which
      supports our hypothesis. By setting the direction of slow phase of nystagmus
      opposite to the direction of the OKN stimulation, enough angle can be effectively
      made between the gaze and target for the induction of saccade. This is the
      mechanism of reversed OKN response. In darkness and when eyes are closed, IN
      weakens because there is no visual target and neither the saccade for catching up
      the target or slow phase for induction of the saccade is needed.

PMID- 30104999
TI  - Home-Based Orolingual Exercise Improves the Coordination of Swallowing and
      Respiration in Early Parkinson Disease: A Quasi-Experimental Before-and-After
      Exercise Program Study.
AB  - Introduction: The coordination of swallowing and respiration is important for
      safety swallowing without aspiration. This coordination was affected in Parkinson
      disease (PD). A noninvasive assessment tool was used to investigate the effect of
      an easy-to-perform and device-free home-based orolingual exercise (OLE) program
      on swallowing and respiration coordination in patients with early-stage PD.
      Materials and Methods: This study had a quasi-experimental before-and-after
      exercise program design. Twenty six patients with early-stage PD who were aged
      62.12 +/- 8.52 years completed a 12-week home-based OLE program. A noninvasive
      assessment tool was used to evaluate swallowing and respiration. For each
      patient, we recorded and analyzed 15 swallows (3 repeats of 5 water boluses: 1,
      3, 5, 10, and 20 mL) before and after the home-based OLE program. Oropharyngeal
      swallowing and its coordination with respiration were the outcome measures. The
      frequency of piecemeal deglutition, pre- and post-swallowing respiratory phase
      patterns, and parameters of oropharyngeal swallowing and respiratory signals
      (swallowing respiratory pause [SRP], onset latency [OL], total excursion time
      [TET], excursion time [ET], second deflexion, amplitude, and duration of
      submental sEMG activity, and amplitude of laryngeal excursion) were examined.
      Results: The rate of piecemeal deglutition decreased significantly when
      swallowing 10- and 20-mL water boluses after the program. In the 1-mL water bolus
      swallowing trial, the rate of protective pre- and post-swallowing respiratory
      phase patterns was significantly higher after the program. For the parameters of
      oropharyngeal swallowing and respiratory signals, only the amplitude of laryngeal
      excursion was significantly lower after the program. Moreover, the volume of the
      water bolus significantly affected the SRP and duration of submental sEMG when
      patients swallowed three small water bolus volumes (1, 3, and 5 mL). Conclusion:
      The home-based OLE program improved swallowing and its coordination with
      respiration in patients with early-stage PD, as revealed using a noninvasive
      method. This OLE program can serve as a home-based program to improve swallowing
      and respiration coordination in patients with early-stage PD.

PMID- 30105000
TI  - Access to End-of Life Parkinson's Disease Patients Through Patient-Centered
      Integrated Healthcare.
AB  - Background: Palliative care in Parkinson's Disease (PD) patients considerably
      differs from palliative care in oncology patients. Integrated care models are a
      concept to support patients and improve management of PD symptoms. However, it is
      not known if the access to PD patients at the end of life can be achieved through
      integrated care models. Aim: To analyze an integrated model of care for PD
      patients with the aim to identify if this integrated model of care has access to
      PD patients at the end of life. Material and Methods: The Cologne Parkinson's
      network was designed as a randomized, controlled prospective clinical trial in
      order to increase quality of life of PD patients. This innovative model of care
      integrated a neurologist in private practice, a movement disorder specialist of
      the University Hospital and a PD nurse. Mortality rates of PD patients during the
      study period of 6 months were registered and compared with mortality rates of the
      general population of Germany according to the Federal Statistical Office of
      Germany. The retrospective post-hoc analysis was conducted after completion of
      the initial study at the University Hospital and neurologists' practices in the
      greater area of Cologne, Germany. Eligible patients had a diagnosis of idiopathic
      PD and were aged 25-85 years. Results: Parkinson's Disease patients in this trial
      had an even slightly lower mortality rate as the general population (1.66 v.
      2.1%). These results are contradictory and speak for a substantial proportion of
      late-stage disease patients, who have not been adequately included in this study
      or have been better treated within this trial. The mean disease duration of
      patients in this study was around 6 years which resembles the lower range of the
      mean disease duration at death of PD patients in general. Conclusions: The
      results of our post-hoc analysis show, that accessing PD patients in the last
      phase of their disease is extremely difficult and nearly fails in spite of an
      integrated care approach. Reasons for poor access and loss of follow-up at the
      end of life have to be identified and care models for PD patients until the end
      of life should be developed urgently.

PMID- 30105003
TI  - Dietary Copper Intake and Its Association With Telomere Length: A Population
      Based Study.
AB  - Background: Telomere is regarded as the fundamental aspect of cellular aging and
      copper is recognized as one of the most essential trace elements. The role of
      dietary copper intake in telomere length maintenance is seldom examined. This
      study aims to investigate if telomere length is to be associated with daily
      dietary copper intake. Methods: We used epidemiological data from a large
      national population-based health and nutrition survey. Dietary intake was
      assessed during the 24-h period before the interview date when blood sample was
      collected. Telomere length was measured from blood leukocyte using PCR method.
      The relationship between telomere length and dietary copper intake was assessed
      using multivariable linear regression models. We also examined if obesity,
      measured by body mass index, could modify the observed association. Results:
      There are 7,324 participants had both leukocyte telomere length measured and
      dietary copper intake assessed, around 48.0% of them were men. Telomere length
      was longer in women than that in men (1.05 +/- 0.26 vs. 1.00 +/- 0.26 T/S ratio),
      while dietary copper intake was less in women than that in men (1.12 +/- 0.80 vs.
      1.51 +/- 1.61 mg). After controlling for age, sex, ethnicity, physical activity,
      current smoking status, hypertension, cardiovascular diseases, and body mass
      index in the multivariable linear regression models, one unit increase of log
      transformed dietary copper intake was significantly associated with longer
      telomere length (beta = 0.02, 95% confidence interval: 0.01, 0.04). We did not
      find a significant sex difference for this association. Conclusions: Dietary
      copper intake was significantly associated telomere length.The role of copper in
      human health might be involved in biological aging process.

PMID- 30105002
TI  - Ghrelin and Its Receptors in Gilthead Sea Bream: Nutritional Regulation.
AB  - Ghrelin is involved in the regulation of growth in vertebrates through
      controlling different functions, such as feed intake, metabolism, intestinal
      activity or growth hormone (Gh) secretion. The aim of this work was to identify
      the sequences of preproghrelin and Ghrelin receptors (ghsrs), and to study their
      responses to different nutritional conditions in gilthead sea bream (Sparus
      aurata) juveniles. The structure and phylogeny of S. aurata preproghrelin was
      analyzed, and a tissue screening was performed. The effects of 21 days of fasting
      and 2, 5, 24 h, and 7 days of refeeding on plasma levels of Ghrelin, Gh and Igf
      1, and the gene expression of preproghrelin, ghsrs and members of the Gh/Igf-1
      system were determined in key tissues. preproghrelin and the receptors are well
      conserved, being expressed mainly in stomach, and in the pituitary and brain,
      respectively. Twenty-one days of fasting resulted in a decrease in growth while
      Ghrelin plasma levels were elevated to decrease at 5 h post-prandial when
      pituitary ghsrs expression was minimum. Gh in plasma increased during fasting and
      slowly felt upon refeeding, while plasma Igf-1 showed an inverse profile.
      Pituitary gh expression augmented during fasting reaching maximum levels at 1 day
      post-feeding while liver igf-1 expression and that of its splice variants
      decreased to lowest levels. Liver Gh receptors expression was down-regulated
      during fasting and recovered after refeeding. This study demonstrates the
      important role of Ghrelin during fasting, its acute down-regulation in the post
      prandial stage and its interaction with pituitary Ghsrs and Gh/Igf-1 axis.

PMID- 30105001
TI  - Critical Enzymatic Functions of FTO in Obesity and Cancer.
AB  - Fat mass and obesity-associated protein (FTO) single-nucleotide polymorphisms
      (SNPs) have been linked to increased body mass and obesity in humans by genome
      wide association studies (GWAS) since 2007. Although some recent studies suggest
      that the obesity-related SNPs in FTO influence obesity susceptibility likely
      through altering the expression of the adjacent genes such as IRX3 and RPGRIP1L,
      rather than FTO itself, a solid link between the SNP risk genotype and the
      increased FTO expression in both human blood cells and fibroblasts has been
      reported. Moreover, multiple lines of evidence have demonstrated that FTO does
      play a critical role in the regulation of fat mass, adipogenesis, and body
      weight. Epidemiology studies also showed a strong association of FTO SNPs and
      overweight/obesity with increased risk of various types of cancers. As the first
      identified messenger RNA N6-methyladenosine (m6A) demethylase, FTO has been shown
      recently to play m6A-dependent roles in adipogenesis and tumorigenesis
      (especially in the development of leukemia and glioblastoma). Given the critical
      roles of FTO in cancers, the development of selective and effective inhibitors
      targeting FTO holds potential to treat cancers. This mini review discusses the
      roles and underlying molecular mechanisms of FTO in both obesity and cancers, and
      also summarizes recent advances in the development of FTO inhibitors.

PMID- 30105005
TI  - Melatonin Improves Laying Performance by Enhancing Intestinal Amino Acids
      Transport in Hens.
AB  - The high concentration of melatonin (MEL) in the intestinal mucosa suggests that
      it has a special physiological function in intestine. In hens, previous studies
      have shown that MEL treatment promoted egg-laying performance. Considering the
      importance of amino acids (AA) for egg formation, we hypothesized that MEL may
      enhance the intestinal absorption of AA from the feed, thus promoting egg laying
      performance. In this study, we supplemented the hens with MEL for two consecutive
      weeks. The results showed that, compared with control group, feeding with 0.625
      mg MEL/kg diets gave rise to higher egg laying rate (by 4.3%, P = 0.016),
      increased eggshell thickness (by 16.9%, P < 0.01) and albumen height (by 4.5%, P
      = 0.042). Meanwhile, feeding with 0.625 and 2.5 mg MEL/kg diets could
      significantly increase serum levels of aspartic acid, threonine, serine, glutamic
      acid, glycine, alanine, isoleucine, leucine, tyrosine, phenylalanine, lysine,
      histidine, arginine, and proline. Furthermore, a 0.625 mg MEL/kg diets could
      significantly increase the expression of PepT1 (by 3949.9%), B0AT (by 6045.9%),
      b0, +AT (by 603.5%), and EAAT3 (by 412.7%) in the jejunum. Additionally, in the
      cultured intestinal crypt "organoids," treatment with 0.5 MUM MEL could
      significantly enhance the expression of PepT1, b0, +AT and EAAT3 mRNAs by 35.4%,
      110.0%, and 160.1%, respectively. Detection of MEL concentration in serum and
      intestinal fluid suggested that lower dosage of MEL feeding was mainly acted on
      intestine locally, and further increased intestinal antioxidases (GPx-3, SOD-1 or
      PRDX-3) mRNA expression. Taken together, we demonstrated that MEL feeding in
      laying hens could locally promote the expression and function of AA transporter
      in small intestine by up-regulating antioxidases expression, and finally elevate
      laying performance.

PMID- 30105004
TI  - O-GlcNAc: A Sweetheart of the Cell Cycle and DNA Damage Response.
AB  - The addition and removal of O-linked N-acetylglucosamine (O-GlcNAc) to and from
      the Ser and Thr residues of proteins is an emerging post-translational
      modification. Unlike phosphorylation, which requires a legion of kinases and
      phosphatases, O-GlcNAc is catalyzed by the sole enzyme in mammals, O-GlcNAc
      transferase (OGT), and reversed by the sole enzyme, O-GlcNAcase (OGA). With the
      advent of new technologies, identification of O-GlcNAcylated proteins, followed
      by pinpointing the modified residues and understanding the underlying molecular
      function of the modification has become the very heart of the O-GlcNAc biology. O
      GlcNAc plays a multifaceted role during the unperturbed cell cycle, including
      regulating DNA replication, mitosis, and cytokinesis. When the cell cycle is
      challenged by DNA damage stresses, O-GlcNAc also protects genome integrity via
      modifying an array of histones, kinases as well as scaffold proteins. Here we
      will focus on both cell cycle progression and the DNA damage response, summarize
      what we have learned about the role of O-GlcNAc in these processes and envision a
      sweeter research future.

PMID- 30105007
TI  - Systems Biology Reveals Relevant Gaps in Fc-gammaR Expression, Impaired
      Regulatory Cytokine Microenvironment Interfaced With Anti-Trypanosoma cruzi IgG
      Reactivity in Cardiac Chagas Disease Patients.
AB  - The systems biology approach has become an innovative tool when it comes to
      shedding light on the complex immune response underlying the
      development/maintenance of distinct clinical forms of Chagas disease. The goal of
      this study was to describe an integrative overview of Fc-gammaR expression,
      cytokine microenvironment and anti-Trypanosoma cruzi IgG interface in
      indeterminate-(IND) and cardiac-(CARD) patients. Data demonstrated that IND
      displayed an overall higher Fcgamma-R expression (CD16; CD32; CD64) on
      neutrophils-(NEU), along with (CD16; CD64) on monocytes-(MON) as compared to
      CARD. Additionally, CARD presented an increased expression of CD32 in B-cells.
      While preserved frequency of IL-10-producing cells was observed in IND, decreased
      levels of IL-10+ phagocytes and enhanced TNF+ MON and NK-cells were observed in
      CARD. T. cruzi-antigen recall in vitro induces a general decrease of Fc-gammaR
      expression in Chagas disease patients, especially in CARD. Moreover, T. cruzi
      antigen stimuli triggered a concomitant increase of IFN-gamma+NEU/TNF+NK-cells
      and IL-10+MON/IL-10+B-cells in IND. Biomarker signatures further emphasized the
      contrasting Fc-gammaR expression and cytokine microenvironment observed in Chagas
      disease patients with distinct clinical forms. Up-regulation of Fc-gammaR
      expression (CD16 on NEU;MON;NK) was observed in IND, whereas a general decrease
      was reported for CARD. Moreover, while a mixed cytokine microenvironment (TNF; IL
      10) was observed in IND, CARD presented a contrasting profile with up-regulation
      of TNF+NEU and IL-12+NEU. Integrative network analysis revealed a distinct
      assemblage of biomarkers, with CARD presenting a large number of negative
      internode connectivity in comparison with IND. The relevant gaps in Fc-gammaR
      expression and impaired regulatory cytokine microenvironment interfaced with the
      anti-T. cruzi IgG reactivity throughout an exacerbated negative connectivity may
      account for the development/maintenance of the clinical status of cardiac Chagas
      disease.

PMID- 30105006
TI  - The Empirical Fluctuation Pattern of E. coli Division Control.
AB  - In physics, it is customary to represent the fluctuations of a stochastic system
      at steady state in terms of linear response to small random perturbations.
      Previous work has shown that the same framework describes effectively the trade
      off between cell-to-cell variability and correction in the control of cell
      division of single E. coli cells. However, previous analyses were motivated by
      specific models and limited to a subset of the measured variables. For example,
      most analyses neglected the role of growth rate variability. Here, we take a
      comprehensive approach and consider several sets of available data from both
      microcolonies and microfluidic devices in different growth conditions. We
      evaluate all the coupling coefficients between the three main measured variables
      (interdivision times, cell sizes and individual-cell growth rates). The linear
      response framework correctly predicts consistency relations between a priori
      independent experimental measurements, which confirms its validity. Additionally,
      the couplings between the cell-specific growth rate and the other variables are
      typically non zero. Finally, we use the framework to detect signatures of
      mechanisms in experimental data involving growth rate fluctuations, finding that
      (1) noise-generating coupling between size and growth rate is a consequence of
      inter-generation growth rate correlations and (2) the correlation patterns agree
      with a near-adder model where the added size has a dependence on the single-cell
      growth rate. Our findings define relevant constraints that any theoretical
      description should reproduce, and will help future studies aiming to falsify some
      of the competing models of the cell cycle existing today in the literature.

PMID- 30105008
TI  - "Do It Yourself" Microbial Cultivation Techniques for Synthetic and Systems
      Biology: Cheap, Fun, and Flexible.
AB  - With the emergence of inexpensive 3D printing technology, open-source platforms
      for electronic prototyping and single-board computers, "Do it Yourself" (DIY)
      approaches to the cultivation of microbial cultures are becoming more feasible,
      user-friendly, and thus wider spread. In this perspective, we survey some of
      these approaches, as well as add-on solutions to commercial instruments for
      synthetic and system biology applications. We discuss different cultivation
      designs, including capabilities and limitations. Our intention is to encourage
      the reader to consider the DIY solutions. Overall, custom cultivation devices
      offer controlled growth environments with in-line monitoring of, for example,
      optical density, fluorescence, pH, and dissolved oxygen, all at affordable
      prices. Moreover, they offer a great degree of flexibility for different
      applications and requirements and are fun to design and construct. We include
      several illustrative examples, such as gaining optogenetic control and adaptive
      laboratory evolution experiments.

PMID- 30105009
TI  - Metagenomic Evidence of Microbial Community Responsiveness to Phosphorus and
      Salinity Gradients in Seagrass Sediments.
AB  - Sediment microorganisms can have profound influence on productivity and
      functioning of marine ecosystems through their critical roles in regulating
      biogeochemical processes. However, the identity of sediment microorganisms that
      mediate organic matter turnover and nutrient cycling in seagrass sediments is
      only poorly understood. Here, we used metagenomic sequencing to investigate
      shifts in the structure and functioning of the microbial community of seagrass
      sediments across a salinity and phosphorus (P) availability gradient in Shark
      Bay, WA, Australia. This iconic ecosystem is oligotrophic and hypersaline with
      abundant seagrass meadows that directly contribute Shark Bay's status as a World
      Heritage Site. We show that sediment phosphonate metabolism genes as well as
      enzyme activities increase in hypersaline conditions with lower soluble reactive
      phosphate in the water column. Given that sediment organic P content is also
      highest where P concentrations in the water column are low, we suggest that
      microbial processing of organic P can contribute to the P requirements of
      seagrasses at particularly oligotrophic sites. Seagrass meadows are often highly
      productive in oligotrophic waters, and our findings suggest that an increase in
      the functional capacity of microbial communities in seagrass sediments to break
      down organic P may contribute to the high productivity of seagrass meadows under
      oligotrophic conditions. When compared to soil and sediment metagenomes from
      other aquatic and terrestrial ecosystems, we also show microbial communities in
      seagrass sediments have a disproportionately high abundance of putative
      phosphorus and sulfur metabolism genes, which may have played an important
      evolutionary role in allowing these angiosperms to recolonize the marine
      environment and prosper under oligotrophic conditions.

PMID- 30105010
TI  - A Novel Microbial Culture Chamber Co-cultivation System to Study Algal-Bacteria
      Interactions Using Emiliania huxleyi and Phaeobacter inhibens as Model Organisms.
AB  - Our understanding of microbial natural environments combines in situ
      experimentation with studies of specific interactions in laboratory-based setups.
      The purpose of this work was to develop, build and demonstrate the use of a
      microbial culture chamber enabling both in situ and laboratory-based studies. The
      design uses an enclosed chamber surrounded by two porous membranes that enables
      the comparison of growth of two separate microbial populations but allowing free
      exchange of small molecules. Initially, we tested if the presence of the
      macroalga Fucus vesiculosus inside the chamber affected colonization of the outer
      membranes by marine bacteria. The alga did indeed enrich the total population of
      colonizing bacteria by more than a factor of four. These findings lead us to
      investigate the effect of the presence of the coccolithophoric alga Emiliania
      huxleyi on attachment and biofilm formation of the marine bacterium Phaeobacter
      inhibens DSM17395. These organisms co-exist in the marine environment and have a
      well-characterized interdependence on secondary metabolites. P. inhibens attached
      in significantly higher numbers when having access to E. huxleyi as compared to
      when exposed to sterile media. The experiment was carried out using a wild type
      (wt) strain as well as a TDA-deficient strain of P. inhibens. The ability of the
      bacterium to produce the antibacterial compound, tropodithietic acid (TDA)
      influenced its attachment since the P. inhibens DSM17395 wt strain attached in
      higher numbers to a surface within the first 48 h of incubation with E. huxleyi
      as compared to a TDA-negative mutant. Whilst the attachment of the bacterium to a
      surface was facilitated by presence of the alga, however, we cannot conclude if
      this was directly affected by the algae or whether biofilm formation was
      dependent on the production of TDA by P. inhibens, which has been implied by
      previous studies. In the light of these results, other applications of immersed
      culture chambers are suggested.

PMID- 30105011
TI  - Investigating Effects of Tulathromycin Metaphylaxis on the Fecal Resistome and
      Microbiome of Commercial Feedlot Cattle Early in the Feeding Period.
AB  - The objective was to examine effects of treating commercial beef feedlot cattle
      with therapeutic doses of tulathromycin, a macrolide antimicrobial drug, on
      changes in the fecal resistome and microbiome using shotgun metagenomic
      sequencing. Two pens of cattle were used, with all cattle in one pen receiving
      metaphylaxis treatment (800 mg subcutaneous tulathromycin) at arrival to the
      feedlot, and all cattle in the other pen remaining unexposed to parenteral
      antibiotics throughout the study period. Fecal samples were collected from 15
      selected cattle in each group just prior to treatment (Day 1), and again 11 days
      later (Day 11). Shotgun sequencing was performed on isolated metagenomic DNA, and
      reads were aligned to a resistance and a taxonomic database to identify
      alignments to antimicrobial resistance (AMR) gene accessions and microbiome
      content. Overall, we identified AMR genes accessions encompassing 9 classes of
      AMR drugs and encoding 24 unique AMR mechanisms. Statistical analysis was used to
      identify differences in the resistome and microbiome between the untreated and
      treated groups at both timepoints, as well as over time. Based on composition and
      ordination analyses, the resistome and microbiome were not significantly
      different between the two groups on Day 1 or on Day 11. However, both the
      resistome and microbiome changed significantly between these two sampling dates.
      These results indicate that the transition into the feedlot-and associated
      changes in diet, geography, conspecific exposure, and environment-may exert a
      greater influence over the fecal resistome and microbiome of feedlot cattle than
      common metaphylactic antimicrobial drug treatment.

PMID- 30105013
TI  - Potential of Human Norovirus Surrogates and Salmonella enterica Contamination of
      Pre-harvest Basil (Ocimum basilicum) via Leaf Surface and Plant Substrate.
AB  - Fresh produce has been identified as an important vehicle for foodborne pathogen
      transmission and fresh culinary herbs have occasionally been associated with
      human pathogens and illness. In this study, the fate of human NoV surrogates
      [murine norovirus 1 (MNV-1) and Tulane virus (TV)] and three strains of
      Salmonella enterica on pre-harvest basil (Ocimum basilicum) was investigated. The
      persistence after contamination via either leaf surface or plant substrate was
      tested respectively. After 3 days, both MNV-1 and TV on pre-harvest leaves were
      at non-detectable levels (>5.5-log reduction for MNV-1 and >3.3-log reduction for
      TV). The three Salmonella strains showed consistent reductions of 3- to 4-log. At
      day 6 and 9, all the tested samples showed low levels of infectivity which were
      close or below the detection limits (1.7-log PFU/sample leaf for MNV-1 and TV,
      0.7-log CFU/sample leaf for Salmonella) except for S. Thompson FMFP 899, one out
      of three samples showed to maintain present at exceptional high levels (day 6:
      5.5-log CFU/sample leaf; day 9: 6.7-log CFU/sample leaf). Possibilities of
      microbial internalization into the edible parts of basil via the roots was
      demonstrated with both MNV-1 and S. enterica Thompson FMFP 899. The infectivity
      of internalized MNV-1 and S. enterica both decreased to non-detectable levels
      within 9 days after inoculation. Moreover, it should be noticed that very high
      microbial inoculation was used in the experimental set-up (8.46-log PFU/ml of MNV
      1, 8.60-log CFU/ml of S. enterica), which is abnormal in the real-life expected
      contamination scenario. Within the tested scenarios in this study, S. enterica
      contaminated on the adaxial leaf surface of basil plants while in growth, and
      remained/reached a high population of over 6-log CFU/sample leaf after 9 days in
      one out of three samples, thus showed the highest potential for causing foodborne
      infection.

PMID- 30105012
TI  - Fisetin Lowers Streptococcus suis serotype 2 Pathogenicity in Mice by Inhibiting
      the Hemolytic Activity of Suilysin.
AB  - Streptococcus suis serotype 2 is a serious zoonotic pathogen and has attracted
      worldwide attention since the first human case was reported in Denmark in 1968.
      Some virulence factors have been reported to be involved in the pathogenesis of
      the infection caused by Streptococcus suis serotype 2, and then novel strategies
      to identify some anti-virulence compounds which can effectively inhibit the
      pathogenic bacterial infection have recently been reported. Suilysin is an
      essential virulence factor for Streptococcus suis serotype 2 since it creates
      pores in the target cells membranes, which aids bacterial colonization. The
      important role of suilysin in the virulence of Streptococcus suis serotype 2
      renders it an ideal target for designing novel anti-virulence therapeutics. We
      find that fisetin, as a natural flavonoid, is a potent antagonist against
      suilysin-mediated hemolysis. The aim of this study is to evaluate the effect of
      fisetin on the hemolytic activity of suilysin from Streptococcus suis serotype 2.
      Fisetin is found to significantly inhibit the hemolytic activity of suilysin.
      Within the range of effective concentrations, fisetin does not influence the
      growth of Streptococcus suis serotype 2 and the expression of suilysin protein.
      In vitro, fisetin effectively inhibits the death of macrophages (J774A.1 and
      RAW264.7) infected with Streptococcus suis serotype 2 by weakening intracellular
      bacterial multiplication. Animal model experiment shows that fisetin effectively
      improves the survival rate of animals infected with Streptococcus suis serotype
      2. Our findings suggest that fisetin could be used as an antitoxin against
      suilysin and be developed into a promising therapeutic candidate for treating
      Streptococcus suis serotype 2 infection.

PMID- 30105014
TI  - Entry Inhibition and Modulation of Pro-Inflammatory Immune Response Against
      Influenza A Virus by a Recombinant Truncated Surfactant Protein D.
AB  - Surfactant protein D (SP-D) is expressed in the mucosal secretion of the lung and
      contributes to the innate host defense against a variety of pathogens, including
      influenza A virus (IAV). SP-D can inhibit hemagglutination and infectivity of
      IAV, in addition to reducing neuraminidase (NA) activity via its carbohydrate
      recognition domain (CRD) binding to carbohydrate patterns (N-linked mannosylated)
      on NA and hemagglutinin (HA) of IAV. Here, we demonstrate that a recombinant
      fragment of human SP-D (rfhSP-D), containing homotrimeric neck and CRD regions,
      acts as an entry inhibitor of IAV and downregulates M1 expression considerably in
      A549 cells challenged with IAV of H1N1 and H3N2 subtypes at 2 h treatment. In
      addition, rfhSP-D downregulated mRNA levels of TNF-alpha, IFN-alpha, IFN-beta, IL
      6, and RANTES, particularly during the initial stage of IAV infection of A549
      cell line. rfhSP-D also interfered with IAV infection of Madin Darby canine
      kidney (MDCK) cells through HA binding. Furthermore, rfhSP-D was found to reduce
      luciferase reporter activity in MDCK cells transduced with H1+N1 pseudotyped
      lentiviral particles, where 50% of reduction was observed with 10 ug/ml rfhSP-D,
      suggestive of a critical role of rfhSP-D as an entry inhibitor against IAV
      infectivity. Multiplex cytokine array revealed that rfhSP-D treatment of IAV
      challenged A549 cells led to a dramatic suppression of key pro-inflammatory
      cytokines and chemokines. In the case of pH1N1, TNF-alpha, IFN-alpha, IL-10, IL
      12 (p40), VEGF, GM-CSF, and eotaxin were considerably suppressed by rfhSP-D
      treatment at 24 h. However, these suppressive effects on IL-10, VEGF, eotaxin and
      IL-12 (p40) were not so evident in the case of H3N2 subtype, with the exception
      of TNF-alpha, IFN-alpha, and GM-CSF. These data seem to suggest that the extent
      of immunomodulatory effect of SP-D on host cells can vary considerably in a IAV
      subtype-specific manner. Thus, rfhSP-D treatment can downregulate pro
      inflammatory milieu encouraged by IAV that otherwise causes aberrant inflammatory
      cell recruitment leading to cell death and lung damage.

PMID- 30105015
TI  - C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP
      Mediated Monocytic Inflammasome Activation.
AB  - Blood levels of the acute phase reactant C-reactive protein (CRP) are frequently
      measured as a clinical marker for inflammation, but the biological functions of
      CRP are still controversial. CRP is a phosphocholine (PC)-binding pentraxin,
      mainly produced in the liver in response to elevated levels of interleukin-1beta
      (IL-1beta) and of the IL-1beta-dependent cytokine IL-6. While both cytokines play
      important roles in host defense, excessive systemic IL-1beta levels can cause
      life-threatening diseases such as trauma-associated systemic inflammation. We
      hypothesized that CRP acts as a negative feedback regulator of monocytic IL-1beta
      maturation and secretion. Here, we demonstrate that CRP, in association with PC,
      efficiently reduces ATP-induced inflammasome activation and IL-1beta release from
      human peripheral blood mononuclear leukocytes and monocytic U937 cells. Effective
      concentrations are in the range of marginally pathologic CRP levels (IC50 = 4.9
      ug/ml). CRP elicits metabotropic functions at nicotinic acetylcholine (ACh)
      receptors (nAChRs) containing subunits alpha7, alpha9, and alpha10 and suppresses
      the function of ATP-sensitive P2X7 receptors in monocytic cells. Of note, CRP
      does not induce ion currents at conventional nAChRs, suggesting that CRP is a
      potent nicotinic agonist controlling innate immunity without entailing the risk
      of adverse effects in the nervous system. In a prospective study on multiple
      trauma patients, IL-1beta plasma concentrations negatively correlated with
      preceding CRP levels, whereas inflammasome-independent cytokines IL-6, IL-18, and
      TNF-alpha positively correlated. In conclusion, PC-laden CRP is an unconventional
      nicotinic agonist that potently inhibits ATP-induced inflammasome activation and
      might protect against trauma-associated sterile inflammation.

PMID- 30105017
TI  - ASAP - A Webserver for Immunoglobulin-Sequencing Analysis Pipeline.
AB  - Reproducible and robust data on antibody repertoires are invaluable for basic and
      applied immunology. Next-generation sequencing (NGS) of antibody variable regions
      has emerged as a powerful tool in systems immunology, providing quantitative
      molecular information on antibody polyclonal composition. However, major
      computational challenges exist when analyzing antibody sequences, from error
      handling to hypermutation profiles and clonal expansion analyses. In this work,
      we developed the ASAP (A webserver for Immunoglobulin-Seq Analysis Pipeline)
      webserver (https://asap.tau.ac.il). The input to ASAP is a paired-end sequence
      dataset from one or more replicates, with or without unique molecular
      identifiers. These datasets can be derived from NGS of human or murine antibody
      variable regions. ASAP first filters and annotates the sequence reads using
      public or user-provided germline sequence information. The ASAP webserver next
      performs various calculations, including somatic hypermutation level, CDR3
      lengths, V(D)J family assignments, and V(D)J combination distribution. These
      analyses are repeated for each replicate. ASAP provides additional information by
      analyzing the commonalities and differences between the repeats ("joint"
      analysis). For example, ASAP examines the shared variable regions and their
      frequency in each replicate to determine which sequences are less likely to be a
      result of a sample preparation derived and/or sequencing errors. Moreover, ASAP
      clusters the data to clones and reports the identity and prevalence of top
      ranking clones (clonal expansion analysis). ASAP further provides the
      distribution of synonymous and non-synonymous mutations within the V genes
      somatic hypermutations. Finally, ASAP provides means to process the data for
      proteomic analysis of serum/secreted antibodies by generating a variable region
      database for liquid chromatography high resolution tandem mass spectrometry (LC
      MS/MS) interpretation. ASAP is user-friendly, free, and open to all users, with
      no login requirement. ASAP is applicable for researchers interested in basic
      questions related to B cell development and differentiation, as well as applied
      researchers who are interested in vaccine development and monoclonal antibody
      engineering. By virtue of its user-friendliness, ASAP opens the antibody analysis
      field to non-expert users who seek to boost their research with immune repertoire
      analysis.

PMID- 30105016
TI  - Radiation-Induced Transformation of Immunoregulatory Networks in the Tumor
      Stroma.
AB  - The implementation of novel cancer immunotherapies in the form of immune
      checkpoint blockers represents a major advancement in the treatment of cancer,
      and has renewed enthusiasm for identifying new ways to induce antitumor immune
      responses in patients. Despite the proven efficacy of neutralizing antibodies
      that target immune checkpoints in some refractory cancers, many patients do not
      experience therapeutic benefit, possibly owing to a lack of antitumor immune
      recognition, or to the presence of dominant immunosuppressive mechanisms in the
      tumor microenvironment (TME). Recent developments in this field have revealed
      that local radiotherapy (RT) can transform tumors into in situ vaccines, and may
      help to overcome some of the barriers to tumor-specific immune rejection. RT has
      the potential to ignite tumor immune recognition by generating immunogenic
      signals and releasing neoantigens, but the multiple immunosuppressive forces in
      the TME continue to represent important barriers to successful tumor rejection.
      In this article, we review the radiation-induced changes in the stromal
      compartments of tumors that could have an impact on tumor immune attack. Since
      different RT regimens are known to mediate strikingly different effects on the
      multifarious elements of the tumor stroma, special emphasis is given to different
      RT schedules, and the time after treatment at which the effects are measured. A
      better understanding of TME remodeling following specific RT regimens and the
      window of opportunity offered by RT will enable optimization of the design of
      novel treatment combinations.

PMID- 30105019
TI  - Enhanced Immune Responses Conferring Cross-Protection by Skin Vaccination With a
      Tri-Component Influenza Vaccine Using a Microneedle Patch.
AB  - Skin vaccination using biodegradable microneedle patch (MNP) technology in
      vaccine delivery is a promising strategy showing significant advantages over
      conventional flu shots. In this study, we developed an MNP encapsulating a 4M2e
      tFliC fusion protein and two types of whole inactivated influenza virus vaccines
      (H1N1 and H3N2) as a universal vaccine candidate. We demonstrated that mice
      receiving this tri-component influenza vaccine via MNP acquired improved IgG1
      antibody responses with more balanced IgG1/IgG2a antibody responses and enhanced
      cellular immune responses, including increased populations of IL-4 and IFN-gamma
      producing cells and higher frequencies of antigen-specific plasma cells compared
      with intramuscular injection. In addition, stronger germinal center reactions,
      increased numbers of Langerin-positive migratory dendritic cells, and increased
      cytokine secretion were observed in the skin-draining lymph nodes after
      immunization with the tri-component influenza MNP vaccine. The MNP-immunized
      group also possessed enhanced protection against a heterologous reassortant
      A/Shanghai/2013 H7N9 (rSH) influenza virus infection. Furthermore, the sera
      collected from 4M2e-tFliC MNP-immunized mice were demonstrated to have antiviral
      efficacy against reassortant A/Vietnam/1203/2004 H5N1 (rVet) and A/Shanghai/2013
      H7N9 (rSH) virus challenges. The immunological advantages of skin vaccination
      with this tri-component MNP vaccine could offer a promising approach to develop
      an easily applicable and broadly protective universal influenza vaccine.

PMID- 30105020
TI  - Monocyte Subsets: Phenotypes and Function in Tuberculosis Infection.
AB  - Monocytes are critical defense components that play an important role in the
      primary innate immune response. The heterogeneous nature of monocytes and their
      ability to differentiate into either monocyte-derived macrophages or monocyte
      derived dendritic cells allows them to serve as a bridge between the innate and
      adaptive immune responses. Current studies of monocytes based on
      immunofluorescence, single-cell RNA sequencing and whole mass spectrometry finger
      printing reveals different classification systems for monocyte subsets. In
      humans, three circulating monocyte subsets are classified based on relative
      expression levels of CD14 and CD16 surface proteins, namely classical,
      intermediate and non-classical subsets. Transcriptomic analyses of these subsets
      help to define their distinct functional properties. Tuberculosis (TB) is a
      disease instigated by the deadly pathogen Mycobacterium tuberculosis. Current
      research on monocytes in TB has indicated that there are alterations in the
      frequency of intermediate and non-classical subsets suggesting their impact in
      bacterial persistence. In this review, we will focus on these monocyte subsets,
      including their classification, frequency distribution, cytokine profiles, role
      as a biomarker and will comment on future directions for understanding the
      salient phenotypic and functional properties relevant to TB pathogenesis.

PMID- 30105018
TI  - Potential Mechanisms Connecting Purine Metabolism and Cancer Therapy.
AB  - Unrestricted cell proliferation is a hallmark of cancer. Purines are basic
      components of nucleotides in cell proliferation, thus impaired purine metabolism
      is associated with the progression of cancer. The de novo biosynthesis of purine
      depends on six enzymes to catalyze the conversion of phosphoribosylpyrophosphate
      to inosine 5'-monophosphate. These enzymes cluster around mitochondria and
      microtubules to form purinosome, which is a multi-enzyme complex involved in de
      novo purine biosynthesis and purine nucleotides requirement. In this review, we
      highlighted the purine metabolism and purinosome biology with emphasis on the
      therapeutic potential of manipulating of purine metabolism or purinosome in
      cancers. We also reviewed current advances in our understanding of mammalian
      target of rapamycin for regulating purinosome formation or purine metabolism in
      cancers and discussed the future prospects for targeting purinosome to treat
      cancers.

PMID- 30105021
TI  - The Coagulation Factors Fibrinogen, Thrombin, and Factor XII in Inflammatory
      Disorders-A Systematic Review.
AB  - Background: The interaction of coagulation factors has been shown to go beyond
      their traditional roles in hemostasis and to affect the development of
      inflammatory diseases. Key molecular players, such as fibrinogen, thrombin, or
      factor XII have been mechanistically and epidemiologically linked to inflammatory
      disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), and colitis.
      Objectives: To systematically review the evidence for a role of coagulation
      factors, especially factor XII, fibrinogen, and thrombin in inflammatory
      disorders like MS, RA, and bowel disorders. Methods: A systematic literature
      search was done in the PubMed database to identify studies about coagulation
      factors in inflammatory diseases. Original articles and reviews investigating the
      role of the kallikrein-kinin and the coagulation system in mouse and humans were
      included. Results: We identified 43 animal studies dealing with inflammatory
      disorders and factors of the kallikrein-kinin or the coagulation system.
      Different immunological influences are described and novel molecular mechanisms
      linking coagulation and inflammation are reported. Conclusion: A number of
      studies have highlighted coagulation factors to tip the balance between
      hemostasis and thrombosis and between protection from infection and extensive
      inflammation. To optimize the treatment of chronic inflammatory disorders by
      these factors, further studies are necessary.

PMID- 30105023
TI  - B-1a Cell Development in Splenectomized Neonatal Mice.
AB  - B-1a cells are mainly generated from fetal liver progenitor cells, peri- and
      neonatally. The developmental steps and anatomical sites required for these cells
      to become mature B-1a cells remain elusive. We recently described a
      phenotypically distinct transitional B cell subset in the spleen of neonatal mice
      that generated B-1a cells when adoptively transferred. This, in combination with
      findings demonstrating that B-1a cells are lacking in congenitally asplenic mice,
      led us to hypothesize that the neonatal spleen is required for B-1a cell
      development. In accordance with previous reports, we found that B-1a cell numbers
      were reduced in adult mice that had undergone splenectomy compared to after sham
      surgery. In contrast, neonatal splenectomy led to peritoneal B-1a cell
      frequencies comparable to those observed in sham-operated mice until 6 weeks
      after surgery, suggesting that an intact spleen is required for B-1a cell
      maintenance rather than development. To study the role of the prenatal spleen in
      generating B-1a cells, we transferred fetal liver cells from pre-splenic embryos
      [embryonic age 11 (E11) days] into splenectomized recipient mice. B-1a cells were
      generated in the absence of the spleen, albeit at slightly reduced frequencies,
      and populated the peritoneal cavity and bone marrow. Lower bone marrow B-1a cell
      frequencies were also observed both after neonatal and adult splenectomy. These
      results demonstrated that B-1a cells could be generated in the complete absence
      of an intact spleen, but that asplenia led to a decline in these cells,
      suggesting a role of the spleen for maintaining the B-1a compartment.

PMID- 30105022
TI  - Immune Effects of Corticosteroids in Sepsis.
AB  - Sepsis, a life-threatening organ dysfunction, results from a dysregulated host
      response to invading pathogens that may be characterized by overwhelming systemic
      inflammation or some sort of immune paralysis. Sepsis remains a major cause of
      morbidity and mortality. Treatment is nonspecific and relies on source control
      and organ support. Septic shock, the most severe form of sepsis is associated
      with the highest rate of mortality. Two large multicentre trials, undertaken 15
      years apart, found that the combination of hydrocortisone and fludrocortisone
      significantly reduces mortality in septic shock. The corticosteroids family is
      composed of several molecules that are usually characterized according to their
      glucocorticoid and mineralocorticoid power, relative to hydrocortisone. While the
      immune effects of glucocorticoids whether mediated or not by the intracellular
      glucocorticoid receptor have been investigated for several decades, it is only
      very recently that potential immune effects of mineralocorticoids via non-renal
      mineralocorticoid receptors have gained popularity. We reviewed the respective
      role of glucocorticoids and mineralocorticoids in counteracting sepsis-associated
      dysregulated immune systems.

PMID- 30105024
TI  - Notch Signaling Modulates Macrophage Polarization and Phagocytosis Through Direct
      Suppression of Signal Regulatory Protein alpha Expression.
AB  - The Notch pathway plays critical roles in the development and functional
      modulation of myeloid cells. Previous studies have demonstrated that Notch
      activation promotes M1 polarization and phagocytosis of macrophages; however, the
      downstream molecular mechanisms mediating Notch signal remain elusive. In an
      attempt to identify Notch downstream targets in bone marrow-derived macrophages
      (BMDMs) using mass spectrometry, the signal regulatory protein alpha (SIRPalpha)
      appeared to respond to knockout of recombination signal-binding protein Jk (RBP
      J), the critical transcription factor of Notch pathway, in macrophages. In this
      study, we validated that Notch activation could repress SIRPalpha expression
      likely via the Hes family co-repressors. SIRPalpha promoted macrophage M2
      polarization, which was dependent on the interaction with CD47 and mediated by
      intracellular signaling through SHP-1. We provided evidence that Notch signal
      regulated macrophage polarization at least partially through SIRPalpha.
      Interestingly, Notch signal regulated macrophage phagocytosis of tumor cells
      through SIRPalpha but in a SHP-1-independent way. To access the translational
      value of our findings, we expressed the extracellular domains of the mouse
      SIRPalpha (mSIRPalphaext) to block the interaction between CD47 and SIRPalpha. We
      demonstrated that the soluble mSIRPalphaext polypeptides could promote M1
      polarization and increase phagocytosis of tumor cells by macrophages. Taken
      together, our results provided new insights into the molecular mechanisms of
      notch-mediated macrophage polarization and further validated SIRPalpha as a
      target for tumor therapy through modulating macrophage polarization and
      phagocytosis.

PMID- 30105025
TI  - Intravascular Schistosoma mansoni Cleave the Host Immune and Hemostatic Signaling
      Molecule Sphingosine-1-Phosphate via Tegumental Alkaline Phosphatase.
AB  - Schistosomes are parasitic flatworms that infect the vasculature of >200 million
      people around the world. These long-lived parasites do not appear to provoke
      blood clot formation or obvious inflammation around them in vivo. Proteins
      expressed at the host-parasite interface (such as Schistosoma mansoni alkaline
      phosphatase, SmAP) are likely key to these abilities. SmAP is a glycoprotein that
      hydrolyses the artificial substrate p-nitrophenyl phosphate in a reaction that
      requires Mg2+ and at an optimal pH of 9. SmAP additionally cleaves the nucleoside
      monophosphates AMP, CMP, GMP, and TMP, all with a similar Km (~600-650 MUM).
      Living adult worms, incubated in murine plasma for 1 h, alter the plasma
      metabolome; a decrease in sphingosine-1-phosphate (S1P) is accompanied by an
      increase in the levels of its component parts-sphingosine and phosphate. To test
      the hypothesis that schistosomes can hydrolyze S1P (and not merely recruit or
      activate a host plasma enzyme with this function), living intravascular life
      stage parasites were incubated with commercially obtained S1P and cleavage of S1P
      was detected. Parasites whose SmAP gene was suppressed using RNAi were impaired
      in their ability to cleave S1P compared to controls. In addition, recombinant
      SmAP hydrolyzed S1P. Since extracellular S1P plays key roles in controlling
      inflammation and platelet aggregation, we hypothesize that schistosome SmAP, by
      degrading S1P, can regulate the level of this bioactive lipid in the environment
      of the parasites to control these processes in the worm's local environment. This
      is the first report of any parasite being able to cleave S1P.

PMID- 30105027
TI  - Increased iNKT17 Cell Frequency in the Intestine of Non-Obese Diabetic Mice
      Correlates With High Bacterioidales and Low Clostridiales Abundance.
AB  - iNKT cells play different immune function depending on their cytokine-secretion
      phenotype. iNKT17 cells predominantly secrete IL-17 and have an effector and
      pathogenic role in the pathogenesis of autoimmune diseases such as type 1
      diabetes (T1D). In line with this notion, non-obese diabetic (NOD) mice that
      spontaneously develop T1D have an increased percentage of iNKT17 cells compared
      to non-autoimmune strains of mice. The factors that regulate iNKT cell expansion
      and acquisition of a specific iNKT17 cell phenotype are unclear. Here, we
      demonstrate that the percentage of iNKT17 cells is increased in the gut more than
      peripheral lymphoid organs of NOD mice, thus suggesting that the intestinal
      environment promotes iNKT17 cell differentiation in these mice. Increased
      intestinal iNKT17 cell differentiation in NOD mice is associated with the
      presence of pro-inflammatory IL-6-secreting dendritic cells that could contribute
      to iNKT cell expansion and iNKT17 cell differentiation. In addition, we found
      that increased iNKT17 cell differentiation in the large intestine of NOD mice is
      associated with a specific gut microbiota profile. We demonstrated a positive
      correlation between percentage of intestinal iNKT17 cells and bacterial strain
      richness (alpha-diversity) and relative abundance of Bacterioidales strains. On
      the contrary, the relative abundance of the anti-inflammatory Clostridiales
      strains negatively correlates with the intestinal iNKT17 cell frequency.
      Considering that iNKT17 cells play a key pathogenic role in T1D, our data support
      the notion that modulation of iNKT17 cell differentiation through gut microbiota
      changes could have a beneficial effect in T1D.

PMID- 30105026
TI  - Differential Redox State Contributes to Sex Disparities in the Response to
      Influenza Virus Infection in Male and Female Mice.
AB  - Influenza virus replicates intracellularly exploiting several pathways involved
      in the regulation of host responses. The outcome and the severity of the
      infection are thus strongly conditioned by multiple host factors, including age,
      sex, metabolic, and redox conditions of the target cells. Hormones are also
      important determinants of host immune responses to influenza and are recently
      proposed in the prophylaxis and treatment. This study shows that female mice are
      less susceptible than males to mouse-adapted influenza virus (A/PR8/H1N1).
      Compared with males, PR8-infected females display higher survival rate (+36%),
      milder clinical disease, and less weight loss. They also have milder
      histopathological signs, especially free alveolar area is higher than that in
      males, even if pro-inflammatory cytokine production shows slight differences
      between sexes; hormone levels, moreover, do not vary significantly with infection
      in our model. Importantly, viral loads (both in terms of viral M1 RNA copies and
      tissue culture infectious dose 50%) are lower in PR8-infected females. An
      analysis of the mechanisms contributing to sex disparities observed during
      infection reveals that the female animals have higher total antioxidant power in
      serum and their lungs are characterized by increase in (i) the content and
      biosynthesis of glutathione, (ii) the expression and activity of antioxidant
      enzymes (peroxiredoxin 1, catalase, and glutathione peroxidase), and (iii) the
      expression of the anti-apoptotic protein Bcl-2. By contrast, infected males are
      characterized by high expression of NADPH oxidase 4 oxidase and phosphorylation
      of p38 MAPK, both enzymes promoting viral replication. All these factors are
      critical for cell homeostasis and susceptibility to infection. Reappraisal of the
      importance of the host cell redox state and sex-related effects may be useful in
      the attempt to develop more tailored therapeutic interventions in the fight
      against influenza.

PMID- 30105028
TI  - Innate Immunity of Neonates and Infants.
AB  - Many important events occur at birth. The fetus is suddenly removed from a
      protected intra-uterine environment that is aquatic, warm, and nearly sterile, to
      the dry, cold external world laden with microbes. To survive, the neonate must
      interact with many organisms, making use of some, while vigorously defending
      against the others like a nation conducting trade with friendly countries and
      guarding against hostile ones from invading it, waging wars if necessary.
      Although, the neonatal immune system is plastic, however, it is highly tolerant
      which is due to both the fetal development during gestation as well as
      significant sudden changes in fetal environment and enormous exposure to the new
      antigens and intestinal bacteria and their products. This "quiescent mode" of
      innate immune system is part of a highly regulated process to fulfill all
      requirements of multi-layered process of early life, implemented effectively
      through the cells of innate immune system. While, most of the neonatal innate
      immune cells (e.g., neutrophils and monocytes) present contained activity and
      lower frequencies compared to their adult counterparts, innate lymphoid cells
      (ILCs), a distinct cellular component of innate immunity, show higher level of
      activity and presence during period of infancy compared to later stages of life
      and adulthood, which may suggest a role for ILCs in variable susceptibility to
      certain conditions during life time. In this review, while we focus on the
      characteristics and status of ILCs in neonatal immune system, we also draw an
      analogy from a national defense perspective because of the great similarities
      between that and the immune system by providing the known biological counterparts
      of all five core operational elements, the five Ds of defense, detection,
      discrimination, deployment, destruction, and de-escalation, with special focus on
      innate immunity, maternal support, and influence during the neonatal and infancy
      periods.

PMID- 30105029
TI  - Schistosoma mansoni SmKI-1 or Its C-Terminal Fragment Induces Partial Protection
      Against S. mansoni Infection in Mice.
AB  - Current schistosomiasis control strategies are mainly based on chemotherapy, but
      the development of a vaccine against this parasitic disease would contribute to a
      long-lasting decrease in disease spectrum and transmission. When it comes to
      vaccine candidates, several genes encoding Schistosoma mansoni proteins expressed
      at the mammalian host-parasite interface have been tested. Among the most
      promising molecules are the proteins present on the tegument and digestive tract
      of the parasite. In this study, we evaluate the potential of SmKI-1, the first
      Kunitz-type protease inhibitor functionally characterized in S. mansoni, as a
      vaccine candidate. Bioinformatic analysis points to the C-terminal fragment as
      the main region of the molecule responsible for the development of a potential
      protective immune response induced by SmKI-1. Therefore, for the vaccine
      formulations, we produced the recombinant (r) SmKI-1 and two different fragments,
      its Kunitz (KI) domain and its C-terminal tail. First, we demonstrate that mice
      immunized with recombinant SmKI-1 (rSmKI-1) or its fragments, formulated with
      Freund's adjuvant, induced the production of IgG-specific antibodies. Further,
      all vaccine formulations tested here also induced a Th1-type of immune response,
      as suggested by the production of IFN-gamma and TNF-alpha by protein-stimulated
      cultured splenocytes. However, the protective effect conferred by vaccination was
      only observed in groups which received rSmKI-1 or C-terminal domain vaccines.
      Mice administered with rSmKI-1 demonstrated reduction of 47% in worm burden, 36%
      in egg number in mouse livers, and 33% in area of liver granulomas. Additionally,
      mice injected with C-terminal domain showed reduction of 28% in worm burden, 38%
      in egg number in liver, and 25% in area of liver granulomas. In contrast, KI
      domain immunization was unable to reduce worm burden and ameliorate liver
      pathology after challenge infection. Taken together, our data demonstrated that
      SmKI-1 is a potential candidate for use in a vaccine to control schistosomiasis,
      and its C-terminal tail seems to be the main region of the molecule responsible
      for protection conferred by this antigen.

PMID- 30105030
TI  - Azithromycin Clears Bordetella pertussis Infection in Mice but Also Modulates
      Innate and Adaptive Immune Responses and T Cell Memory.
AB  - Treatment with the macrolide antibiotic azithromycin (AZM) is an important
      intervention for controlling infection of children with Bordetella pertussis and
      as a prophylaxis for preventing transmission to family members. However,
      antibiotics are known to have immunomodulatory effects independent of their
      antimicrobial activity. Here, we used a mouse model to examine the effects of AZM
      treatment on clearance of B. pertussis and induction of innate and adaptive
      immunity. We found that treatment of mice with AZM either 7 or 14 days post
      challenge effectively cleared the bacteria from the lungs. The numbers of innate
      immune cells in the lungs were significantly reduced in antibiotic-treated mice.
      Furthermore, AZM reduced the activation status of macrophages and dendritic
      cells, but only in mice treated on day 7. Early treatment with antibiotics also
      reduced the frequency of tissue-resident T cells and IL-17-producing cells in the
      lungs. To assess the immunomodulatory effects of AZM independent of its
      antimicrobial activity, mice were antibiotic treated during immunization with a
      whole cell pertussis (wP) vaccine. Protection against B. pertussis induced by
      immunization with wP was slightly reduced in AZM-treated mice. Antibiotic-treated
      wP-immunized mice had reduced numbers of lung-resident memory CD4 T cells and IL
      17-production and reduced CD49d expression on splenic CD4 T cells after
      challenge, suggestive of impaired CD4 T cell memory. Taken together these results
      suggest that AZM can modulate the induction of memory CD4 T cells during B.
      pertussis infection, but this may in part be due to the clearance of B. pertussis
      and resulting loss of components that stimulate innate and adaptive immune
      response.

PMID- 30105032
TI  - Adipocytes Promote Early Steps of Breast Cancer Cell Dissemination via
      Interleukin-8.
AB  - Fat is a major tissue component in human breast cancer (BC). Whether breast
      adipocytes (BAd) affect early stages of BC metastasis is yet unknown. BC
      progression is dependent on angiogenesis and inflammation, and interleukin-8 (IL
      8) and vascular endothelial growth factor (VEGF) are key regulators of these
      events. Here, we show that BAd increased the dissemination of estrogen receptor
      positive BC cells (BCC) in vivo in the zebrafish model of metastasis, while
      dissemination of the more aggressive and metastatic BCC such as estrogen receptor
      negative was unaffected. While anti-VEGF and anti-IL-8 exhibited equal inhibition
      of angiogenesis at the primary tumor site, anti-IL-8 reduced BCC dissemination
      whereas anti-VEGF had minor effects on this early metastatic event.
      Mechanistically, overexpression of cell-adhesion molecules in BCC and neutrophils
      via IL-8 increased the dissemination of BCC. Importantly, the extracellular in
      vivo levels of IL-8 were 40-fold higher than those of VEGF in human BC. Our
      results suggest that IL-8 is a clinical relevant and promising therapeutic target
      for human BC.

PMID- 30105031
TI  - Invariant Natural Killer T and Mucosal-Associated Invariant T Cells in Asthmatic
      Patients.
AB  - Recent studies have highlighted the heterogeneity of asthma. Distinct patient
      phenotypes (symptoms, age at onset, atopy, and lung function) may result from
      different pathogenic mechanisms, including airway inflammation, remodeling, and
      immune and metabolic pathways in a specific microbial environment. These
      features, which define the asthma endotype, may have significant consequences for
      the development and progression of the disease. Asthma is generally associated
      with Th2 cells, which produce a panel of cytokines (IL-4, IL-5, IL-13) that act
      in synergy to drive lung inflammatory responses, mucus secretion, IgE production,
      and fibrosis, causing the characteristic symptoms of asthma. In addition to
      conventional CD4+ T lymphocytes, other T-cell types can produce Th2 or Th17
      cytokines rapidly. Promising candidate cells for studies of the mechanisms
      underlying the pathophysiology of asthma are unconventional T lymphocytes, such
      as invariant natural killer T (iNKT) and mucosal-associated invariant T (MAIT)
      cells. This review provides an overview of our current understanding of the
      impact of iNKT and MAIT cells on asthmatic inflammation, focusing particularly on
      pediatric asthma.

PMID- 30105033
TI  - Uncovering the Mysteries of Langerhans Cells, Inflammatory Dendritic Epidermal
      Cells, and Monocyte-Derived Langerhans Cell-Like Cells in the Epidermis.
AB  - The identity of Langerhans cells (LCs) has been called into question of late due
      to the increasing evidence that LCs originate from macrophage lineage instead of
      dendritic cell (DC) lineage as previously thought. For many years, LCs have been
      assumed to be DCs due to its migratory capabilities. However, recent studies have
      demonstrated that LCs are from macrophage lineage of the adult fetal liver (FL)
      progenitor. Bona fide LCs are now considered tissue-resident macrophages as they
      originate from the FL as shown by fate mapping models. In recent years, studies
      have shown that there are three types of antigen-presenting cells present in the
      epidermis, such as LCs, monocyte-derived LC-like cells, and inflammatory
      dendritic epidermal cells (IDECs). Of these, LC-like cells have been
      characterized in both human and mouse studies, while IDECs have only been
      described in human studies. This has shed a new light on the area of epidermal
      macrophages, suggesting that there might be a misidentification and
      misclassification of LCs. IDECs and LC-like cells have been shown to be present
      in both steady state and inflammatory state, but they are present in more
      significant amounts under inflammatory conditions such as atopic dermatitis,
      ultra violet injury, and psoriasis. In this review, we discuss what is already
      known and discuss the possible roles of LCs, LC-like cells, and IDECs during
      inflammation. Most intriguingly, we discuss the possibility of LCs having a dual
      identity as both a macrophage and a DC. This is shown as LCs are the only tissue
      resident macrophage to have shown migratory property-like DCs.

PMID- 30105034
TI  - The Phenotype of Monocytes in Anterior Uveitis Depends on the HLA-B27 Status.
AB  - HLA-B27 is the allele most frequently associated with human anterior uveitis. The
      majority of HLA-B27-positive [acute anterior uveitis (AAU)] patients develop
      clinically distinct symptoms with acute symptomatic onset of flare and a
      recurrent disease course characterized by a massive cellular ocular infiltrate
      during uveitis relapse. By contrast, uveitis in HLA-B27-negative [idiopathic
      anterior uveitis (IAU)] patients tends to develop a clinically less fulminant,
      more chronic, and typically asymptomatic disease course. To analyze systemic
      immune responses in the different uveitis entities, we analyzed peripheral blood
      cells by flow cytometry. In addition, as a pro-inflammatory biomarker serum,
      S100A8/A9 levels were quantified by ELISA from patients with AAU (n = 27) and IAU
      (n = 21), and in healthy controls (n = 30). Data were obtained either during
      active uveitis flare or after 3 months of inactivity. IAU patients showed a
      transiently increased frequency of CD56- and CD163-positive monocytes and of both
      granulocytic myeloid-derived suppressor cells and Th17 cells during active
      uveitis. By contrast, AAU patients showed an elevated frequency of monocytes,
      activated T cells, and elevated S100A8/A9 serum levels during clinically
      quiescent disease. The differentially regulated response of both innate and
      adaptive immune cells in the blood may be related to the clinically distinct
      characteristics of the two different uveitis entities.

PMID- 30105035
TI  - Cancer Cell-Intrinsic PD-1 and Implications in Combinatorial Immunotherapy.
AB  - Programmed death 1 (PD-1) and its two natural ligands PD-L1 and PD-L2 are
      responsible for delivering inhibitory signals that regulate the balance between T
      cell activation, tolerance, and immunopathology. In previous studies, PD-1 was
      found only expressed on the surface of immune cells, such as T cells and B cells
      while PD-1's ligands PD-L1 and PD-L2 were found expressed in some tumor cells.
      However, recent studies revealed intrinsic expression of PD-1 in melanoma and
      some other cancers. In melanoma cells, PD-1 can be activated by its ligand PD-L1
      expressed by tumor cells, modulating downstream mammalian target of rapamycin
      signaling and promoting tumor growth independent of adaptive immunity. In
      addition to melanoma, PD-1 was also detected in liver cancer cells as well as in
      non-small lung cancer cells. Unlike its oncogenic functions in melanoma and
      hepatic carcinoma cells, PD-1 seemed to play a distinct role in lung cancer, as
      blockade of PD-1 instead promoted tumor cells proliferation. Tumor-intrinsic PD-1
      expression seems to be widespread in many tumor types, according to our
      reanalysis on cancer transcriptomic and proteomic data. The multifaceted roles of
      PD-1 in tumor cells beyond immune checkpoint signaling may explain the
      differential therapeutic effects of anti-PD-1 and anti-PD-L1 drugs and provide
      crucial information when developing combinatorial approaches to enhance antitumor
      immunity.

PMID- 30105036
TI  - Elevated Pentraxin 3 in Obese Adipose Tissue Promotes Adipogenic Differentiation
      by Activating Neuropeptide Y Signaling.
AB  - Obesity is accompanied by chronic systemic inflammation characterized by
      macrophage infiltration of obese tissues, an elevated plasma level of
      inflammatory substances, and excessive accumulation of lipids. The pro
      inflammatory factor pentraxin 3 (PTX3) is also elevated in obese tissues,
      suggesting its potential role in adipogenesis. We found by analyzing murine
      preadipocyte 3T3-L1 cells, and human adipocytes derived from mesenchymal stem
      cells, which locally elevated PTX3 in obese adipose tissue augments adipocyte
      differentiation and subsequent lipid accumulation. This occurs via the
      upregulation of adipogenesis-related transcription factors. PTX3 enhanced lipid
      accumulation in murine 3T3-L1 cells by upregulating the expression of
      neuropeptide Y (NPY)/NPY receptor (NPYR) expression in preadipocytes.
      Pharmacological inhibition by NPYR antagonists abolished these effects. NPY also
      promoted the production of reactive oxygen species (ROS), a known trigger of
      adipogenesis. NPYR antagonists as well as antioxidant N-acetylcysteine showed
      anti-adipogenic effects by reducing the ROS levels, indicating that PTX3 mediates
      adipogenesis through NPY-dependent ROS production. These findings suggest that
      PTX3 plays a key role in the development of obesity by enhancing adipocyte
      differentiation and lipid synthesis via NPY/NPYR signaling. These observations
      provide a mechanistic explanation for the adipogenesis mediated by PTX3.

PMID- 30105037
TI  - NLRP3 Inflammasome Participates in Host Response to Neospora caninum Infection.
AB  - Neospora caninum is an intracellular protozoan parasite closely related to
      Toxoplasma gondii that mainly infects canids as the definitive host and cattle as
      the intermediate host, resulting in abortion in cattle and leading to financial
      losses worldwide. Commercial vaccines or drugs are not available for the
      prevention and treatment of bovine neosporosis. Knowledge about the hallmarks of
      the immune response to this infection could form the basis of important
      prevention strategies. The innate immune system first responds to invading
      parasite and subsequently initiates the appropriate adaptive immune response
      against this parasite. Upon infection, activation of host pattern-recognition
      receptors expressed by immune cells triggers the innate immune response. Toll
      like receptors, NOD-like receptors, and C-type lectin receptors play key roles in
      recognizing protozoan parasite. Therefore, we aimed to explore the role of the
      NLRP3 inflammasome during the acute period of N. caninum infection. In vitro
      results showed that N. caninum infection of murine bone marrow-derived
      macrophages activated the NLRP3 inflammasome, accompanied by the release of IL
      1beta and IL-18, cleavage of caspase-1, and induction of cell death. K+ efflux
      induced by N. caninum infection participated in the activation of the
      inflammasome. Infection of mice deficient in NLRP3, ASC, and caspase-1/11
      resulted in decreased production of IL-18 and reduced IFN-gamma in serum.
      Elevated numbers of monocytes/macrophages and neutrophils were found at the
      initial infection site, but they failed to limit N. caninum replication. These
      findings suggest that the NLRP3 inflammasome is involved in the host response to
      N. caninum infection at the acute stage and plays an important role in limiting
      parasite growth, and it may enhance Th1 response by inducing production of IFN
      gamma. These findings may help devise protocols for controlling neosporosis.

PMID- 30105038
TI  - Nitrogen Supply Affects Photosynthesis and Photoprotective Attributes During
      Drought-Induced Senescence in Quinoa.
AB  - Drought during senescence has become more common in Mediterranean climates in
      recent years. Chenopodium quinoa Willd has been identified as tolerant to poor
      soil conditions and drought. Previous observations have found that sufficient
      nitrogen (N) supply mitigates yield losses under terminal drought conditions.
      However, there is no understanding of the mechanisms behind this effect. We
      hypothesized that N up-regulates both photosynthetic and photoprotective elements
      during drought-induced senescence, alleviating the negative impact of drought on
      yield. The role of N supply and terminal drought on photoprotection was tested
      using three Chilean quinoa genotypes from different climatic zones: Faro, UdeC9,
      and BO78. Plants were grown under high nitrogen (HN) or low nitrogen (LN)
      conditions and subjected to terminal drought at the onset of senescence.
      Photosynthetic and photochemical and non-photochemical processes were evaluated
      at both the onset of drought and after 15 days of drought conditions. N
      supplementation modified most of the physiological parameters related to
      photochemical dissipation of energy, photosynthesis, and yield in quinoa. In
      contrast, water restriction did not affect photosynthesis in quinoa, and its
      effect on yield was dependent on the genotype. A significant interaction N * G
      was observed in photosynthesis, relative water content, protein content, Fv/Fm,
      and chlorophylls. In general, Faro was able to maintain higher levels of these
      attributes under LN conditions than UdeC9 and BO78. In addition, the interacting
      effects of N * W regulated the level of most pigments in quinoa as well as the
      photoprotective induction of non-photochemical quenching (NPQ) during senescence.
      During terminal drought at LN conditions, Faro presented a larger NPQ induction
      under drought conditions than UdeC9 and BO78, which was supported by a larger
      zeaxanthin content and de-epoxidation state of the xanthophyll pool.
      Interestingly, BO78 did not induce NPQ in response to drought-induced senescence
      but instead enhanced the content of betacyanins. This response needs to be
      researched in future works. Finally, we observed that LN supply reduced the
      correlationship between the de-epoxidation state of the xanthophyll cycle and
      NPQ. This could be an indication that N supply not only compromised the capacity
      for photosynthetic performance in quinoa plants, but also affected the plasticity
      of thermal dissipation, restricting further changes during drought-induced
      senescence.

PMID- 30105040
TI  - Plastic Population Effects and Conservative Leaf Traits in a Reciprocal
      Transplant Experiment Simulating Climate Warming in the Himalayas.
AB  - Climate warming poses considerable challenges for alpine plant species,
      especially for competitively inferior ones with resource-conservative adaptations
      to cold climates. The Himalayas are warming at rates considerably faster than the
      global average, so it is particularly important to assess how and through which
      mechanisms alpine plant species are affected there. We employed a demographic
      approach in a climate change experiment, where vegetation turfs were transplanted
      reciprocally between the central parts of the study species' (Viola biflora L.
      var. rockiana) range and the warmer range margin, with a temperature difference
      of ca. 1 degrees C. In addition, turfs were also transplanted outside the range
      to warmer habitats, simulating two different scenarios of climate warming, +1 and
      +4 degrees C. Transplanting to warmer sites negatively impacted population growth
      rates (lambda), survival and clonality, but did not affect growth and fecundity,
      while the productivity of the plant community increased. The reciprocal
      transplants to the colder habitat showed the opposite effects, for both V.
      biflora and the plant community, indicating plastic responses of the study
      species, driven by changes in plant-plant competition. However, the leaf traits
      underlying the modeled population growth rates were origin-site specific and not
      affected by the climate-change treatments over the study period, suggesting local
      adaptation of growth form to competition in the warmer range margin, and to
      climate adversity in the colder range center. The transplants outside the present
      species' range showed consistently stronger reductions in population growth rate
      and survival, with mortality of 90-100% in the +4 degrees C treatment. This
      illustrates that climatic changes beyond species' present climatic ranges pose a
      serious risk for range contraction and extinction for Himalayan alpine species in
      the near future. As V. biflora seems mostly limited by competition under warming,
      its persistence in a future climate may become increasingly dependent on keeping
      competitive effects from the surrounding community low, for instance by
      management interventions like grazing and mowing.

PMID- 30105041
TI  - Propagule Pressure Build-Up by the Invasive Hymenoscyphus fraxineus Following Its
      Introduction to an Ash Forest Inhabited by the Native Hymenoscyphus albidus.
AB  - Dieback of European ash, caused by the ascomycete Hymenoscyphus fraxineus
      originating from Asia, has rapidly spread across Europe, and is threatening this
      keystone tree at a continental scale. High propagule pressure is characteristic
      to invasive species. Consistently, the enormous production of windborne
      ascospores by H. fraxineus in an ash forest with epidemic level of disease
      obviously facilitates its invasiveness and long distance spread. To understand
      the rate of build-up of propagule pressure by this pathogen following its local
      introduction, during 2011-2017 we monitored its sporulation at a newly infested
      ash stand in south-western Norway characterized with mild winters and cool
      summers. We also monitored the propagule pressure by Hymenoscyphus albidus, a non
      pathogenic native species that competes for the same sporulation niche with H.
      fraxineus. During the monitoring period, crown condition of ash trees had
      impaired, and 20% of the dominant trees were severely damaged in 2017. H.
      fraxineus showed an exponential increase in spore production between 2012 and
      2015, followed by drastic decline in 2016 and 2017. During 2011-2013, the two
      Hymenoscyphus species showed similar sporulation level, but thereafter spores of
      H. albidus were no longer detected. The data suggest that following local
      introduction, the population of H. fraxineus reaches rapidly an exponential
      growth stage if the local weather conditions are favorable for ascomata
      maturation across years. In the North Atlantic climate, summer temperatures
      critically influence the pathogen infection pressure, warm summers allowing the
      population to grow according to its biotic potential, whereas cold summers can
      cause a drastic decline in propagule pressure.

PMID- 30105042
TI  - Nectar Analysis Throughout the Genus Nicotiana Suggests Conserved Mechanisms of
      Nectar Production and Biochemical Action.
AB  - We have evaluated the floral nectars of nine species from different sections of
      the genus Nicotiana. These nine species effectively cover the genus. We found
      that the nectary glands from these different species showed similar developmental
      regulation with swelling of nectaries during the first half of development and a
      distinct color change in the nectary gland as development approaches anthesis.
      When we examined the composition of the nectar from these nine different species
      we found that they were similar in content. Carbohydrate compositions of these
      various nectars varied between these species with N. bonariensis showing the
      highest and N. sylvestris lowest level of sugars. Based upon the amount of
      carbohydrates, the nectars fell into two groups. We found that hydrogen peroxide
      accumulated in the nectars of each of these species. While all species showed the
      presence of hydrogen peroxide in nectar, the quantitative amounts of hydrogen
      peroxide which was very high in N. rustica and N. bonariensis, suggesting be a
      common characteristic in short flower Nicotiana species. We further found that
      the antioxidant ascorbate accumulated in nectar and beta-carotene accumulated in
      nectaries. beta-carotene was most high in nectaries of N. bonariensis. We also
      examined the presence of proteins in the nectars of these species. The protein
      profile and quantities varied significantly between species, although all species
      have showed the presence of proteins in their nectars. We performed a limited
      proteomic analysis of several proteins from these nectars and determined that
      each of the five abundant proteins examined were identified as Nectarin 1,
      Nectarin 3, or Nectarin 5. Thus, based upon the results found in numerous species
      across the genus Nicotiana, we conclude that the mechanisms identified are
      similar to those mechanisms found in previous studies on ornamental tobacco
      nectars. Further, these similarities are remarkably conserved, throughout the
      genus Nicotiana.

PMID- 30105043
TI  - SiSTL2 Is Required for Cell Cycle, Leaf Organ Development, Chloroplast
      Biogenesis, and Has Effects on C4 Photosynthesis in Setaria italica (L.) P.
      Beauv.
AB  - Deoxycytidine monophosphate deaminase (DCD) is a key enzyme in the de novo dTTP
      biosynthesis pathway. Previous studies have indicated that DCD plays key roles in
      the maintenance of the balance of dNTP pools, cell cycle progression, and plant
      development. However, few studies have elucidated the functions of the DCD gene
      in Panicoideae plants. Setaria has been proposed as an ideal model of Panicoideae
      grasses, especially for C4 photosynthesis research. Here, a Setaria italica
      stripe leaf mutant (sistl2) was isolated from EMS-induced lines of "Yugu1," the
      wild-type parent. The sistl2 mutant exhibited semi-dwarf, striped leaves,
      abnormal chloroplast ultrastructure, and delayed cell cycle progression compared
      with Yugu1. High-throughput sequencing and map-based cloning identified the
      causal gene SiSTL2, which encodes a DCD protein. The occurrence of a single-base
      G to A substitution in the fifth intron introduced alternative splicing, which
      led to the early termination of translation. Further physiological and
      transcriptomic investigation indicated that SiSTL2 plays an essential role in the
      regulation of chloroplast biogenesis, cell cycle, and DNA replication, which
      suggested that the gene has conserved functions in both foxtail millet and rice.
      Remarkably, in contrast to DCD mutants in C3 rice, sistl2 showed a significant
      reduction in leaf cell size and affected C4 photosynthetic capacity in foxtail
      millet. qPCR showed that SiSTL2 had a similar expression pattern to typical C4
      genes in response to a low CO2 environment. Moreover, the loss of function of
      SiSTL2 resulted in a reduction of leaf 13C content and the enrichment of DEGs in
      photosynthetic carbon fixation. Our research provides in-depth knowledge of the
      role of DCD in the C4 photosynthesis model S. italica and proposed new directions
      for further study of the function of DCD.

PMID- 30105044
TI  - Herbivore-Associated Bacteria as Potential Mediators and Modifiers of Induced
      Plant Defense Against Spider Mites and Thrips.
AB  - Induced plant defense, comprising contact with exogenous stimuli, production of
      endogenous signals alerting the plant, associated biochemical cascades, and local
      and/or systemic expression of the defense mechanisms, critically depends on the
      nature of the inducing agents. At large, bio-trophic pathogenic microorganisms
      and viruses usually trigger the salicylate (SA)-mediated pathway, whereas necro
      trophic pathogens and herbivores usually trigger the jasmonate (JA)-mediated
      pathway in plants. The SA- and JA-mediated pathways do not operate independently
      but commonly interfere with each other. Several recent studies revealed abnormal
      plant responses upon herbivore attack in diverse plant-herbivore systems.
      Observed abnormalities range from suppression of the common JA-pathway, induction
      of the SA-pathway to no response, yet the underlying proximate causes and
      ultimate consequences of these variations are elusive. Strikingly, some studies
      provide compelling evidence that anti-herbivore plant responses may decisively
      depend on bacteria associated with the herbivore attacking the plant (HAB for
      herbivore-associated bacteria). HAB may influence herbivore recognition by the
      plant and alter the biochemical cascades inside plants. Here, I report cases in
      point of HAB manipulating induced anti-herbivore plant responses, suggest spatial
      and temporal categorization of HAB, and point at proximate and ultimate aspects
      of plant defense manipulation by HAB. Following, I overview the diversity of HAB
      of spider mites and herbivorous thrips, argue that, considering recently reported
      phenomena of abnormal plant responses upon spider mite attack, some of these HAB
      could represent important, but hitherto largely neglected, mediators/modifiers of
      induced plant defense against spider mites and thrips, and conclude with
      suggestions for future research.

PMID- 30105039
TI  - Why Do Herbivorous Mites Suppress Plant Defenses?
AB  - Plants have evolved numerous defensive traits that enable them to resist
      herbivores. In turn, this resistance has selected for herbivores that can cope
      with defenses by either avoiding, resisting or suppressing them. Several species
      of herbivorous mites, such as the spider mites Tetranychus urticae and
      Tetranychus evansi, were found to maximize their performance by suppressing
      inducible plant defenses. At first glimpse it seems obvious why such a trait will
      be favored by natural selection. However, defense suppression appeared to readily
      backfire since mites that do so also make their host plant more suitable for
      competitors and their offspring more attractive for natural enemies. This,
      together with the fact that spider mites are infamous for their ability to resist
      (plant) toxins directly, justifies the question as to why traits that allow mites
      to suppress defenses nonetheless seem to be relatively common? We argue that this
      trait may facilitate generalist herbivores, like T. urticae, to colonize new host
      species. While specific detoxification mechanisms may, on average, be suitable
      only on a narrow range of similar hosts, defense suppression may be more broadly
      effective, provided it operates by targeting conserved plant signaling
      components. If so, resistance and suppression may be under frequency-dependent
      selection and be maintained as a polymorphism in generalist mite populations. In
      that case, the defense suppression trait may be under rapid positive selection in
      subpopulations that have recently colonized a new host but may erode in
      relatively isolated populations in which host-specific detoxification mechanisms
      emerge. Although there is empirical evidence to support these scenarios, it
      contradicts the observation that several of the mite species found to suppress
      plant defenses actually are relatively specialized. We argue that in these cases
      buffering traits may enable such mites to mitigate the negative side effects of
      suppression in natural communities and thus shield this trait from natural
      selection.

PMID- 30105046
TI  - Characterization of a L-Gulono-1,4-Lactone Oxidase Like Protein in the Floral
      Nectar of Mucuna sempervirens, Fabaceae.
AB  - Floral nectar plays important roles in the interaction between animal-pollinated
      plants and pollinators. Its components include water, sugars, amino acids,
      vitamins, and proteins. Growing empirical evidence shows that most of the
      proteins secreted in nectar (nectarines) are enzymes that can tailor nectar
      chemistry for their animal mutualists or reduce the growth of microorganisms in
      nectar. However, to date, the function of many nectarines remains unknown, and
      very few plant species have had their nectar proteome thoroughly investigated.
      Mucuna sempervirens (Fabaceae) is a perennial woody vine native to China.
      Nectarines from this species were separated using two-dimensional gel
      electrophoresis, and analyzed using mass spectrometry. A L-gulonolactone oxidase
      like protein (MsGulLO) was detected, and the full length cDNA was cloned: it
      codes for a protein of 573 amino acids with a predicted signal peptide. MsGulLO
      has high similarity to L-gulonolactone oxidase 5 (AtGulLO5) in Arabidopsis
      thaliana, which was suggested to be involved in the pathway of ascorbate
      biosynthesis; however, both MsGulLO and AtGulLO5 are divergent from animal L
      gulonolactone oxidases. MsGulLO was expressed mainly in flowers, and especially
      in nectary before blooming. However, cloning and gene expression analysis showed
      that L-galactonolactone dehydrogenase (MsGLDH), a vital enzyme in plant ascorbate
      biosynthesis, was expressed in all of flowers, roots, stems, and especially
      leaves. MsGulLO was purified to near homogeneity from raw MS nectar by gel
      filtration chromatography. The enzyme was determined to be a neutral monomeric
      protein with an apparent molecular mass of 70 kDa. MsGulLO is not a flavin
      containing protein, and has neither L-galactonolactone dehydrogenase activity,
      nor the L-gulonolactone activity that is usual in animal GulLOs. However, it has
      weak oxidase activity with the following substrates: L-gulono-1,4-lactone, L 
      galactono-1,4-lactone, D-gluconic acid-delta-lactone, glucose, and fructose.
      MsGulLO is suggested to function in hydrogen peroxide generation in nectar but
      not in plant ascorbate biosynthesis.

PMID- 30105045
TI  - The High-Affinity Potassium Transporter EpHKT1;2 From the Extremophile Eutrema
      parvula Mediates Salt Tolerance.
AB  - To survive salt stress, plants must maintain a balance between sodium and
      potassium ions. High-affinity potassium transporters (HKTs) play a key role in
      reducing Na+ toxicity through K+ uptake. Eutrema parvula (formerly known as
      Thellungiella parvula), a halophyte closely related to Arabidopsis, has two HKT1
      genes that encode EpHKT1;1 and EpHKT1;2. In response to high salinity, the
      EpHKT1;2 transcript level increased rapidly; by contrast, the EpHKT1;1 transcript
      increased more slowly in response to salt treatment. Yeast cells expressing
      EpHKT1;2 were able to tolerate high concentrations of NaCl, whereas EpHKT1;1
      expressing yeast cells remained sensitive to NaCl. Amino acid sequence alignment
      with other plant HKTs showed that EpHKT1;1 contains an asparagine residue (Asn
      213) in the second pore-loop domain, but EpHKT1;2 contains an aspartic acid
      residue (Asp-205) at the same position. Yeast cells expressing EpHKT1;1, in which
      Asn-213 was substituted with Asp, were able to tolerate high concentrations of
      NaCl. In contrast, substitution of Asp-205 by Asn in EpHKT1;2 did not enhance
      salt tolerance and rather resulted in a similar function to that of AtHKT1 (Na+
      influx but no K+ influx), indicating that the presence of Asn or Asp determines
      the mode of cation selectivity of the HKT1-type transporters. Moreover,
      Arabidopsis plants (Col-gl) overexpressing EpHKT1;2 showed significantly higher
      tolerance to salt stress and accumulated less Na+ and more K+ compared to those
      overexpressing EpHKT1;1 or AtHKT1. Taken together, these results suggest that
      EpHKT1;2 mediates tolerance to Na+ ion toxicity in E. parvula and is a major
      contributor to its halophytic nature.

PMID- 30105048
TI  - Correcting for Population Stratification Reduces False Positive and False
      Negative Results in Joint Analyses of Host and Pathogen Genomes.
AB  - Studies of host genetic determinants of pathogen sequence variations can identify
      sites of genomic conflicts, by highlighting variants that are implicated in
      immune response on the host side and adaptive escape on the pathogen side.
      However, systematic genetic differences in host and pathogen populations can lead
      to inflated type I (false positive) and type II (false negative) error rates in
      genome-wide association analyses. Here, we demonstrate through a simulation that
      correcting for both host and pathogen stratification reduces spurious signals and
      increases power to detect real associations in a variety of tested scenarios. We
      confirm the validity of the simulations by showing comparable results in an
      analysis of paired human and HIV genomes.

PMID- 30105047
TI  - Genome-Wide Signatures of Selection Reveal Genes Associated With Performance in
      American Quarter Horse Subpopulations.
AB  - Selective breeding for athletic performance in various disciplines has resulted
      in population stratification within the American Quarter Horse (QH) breed. The
      goals of this study were to utilize high density genotype data to: (1) identify
      genomic regions undergoing positive selection within and among QH subpopulations;
      (2) investigate haplotype structure within each QH subpopulation; and (3)
      identify candidate genes within genomic regions of interest (ROI), as well as
      biological pathways, predicted to play a role in elite performance in each group.
      For that, 65K SNP genotyping data on 143 elite individuals from 6 QH
      subpopulations (cutting, halter, racing, reining, western pleasure, and working
      cow) were imputed to 2M SNPs. Signatures of selection were identified using FST
      based (di ) and haplotype-based (hapFLK) analyses, accompanied by identification
      of local haplotype structure and sharing within subpopulations (hapQTL). Regions
      undergoing positive selection were identified on all 31 autosomes, and ROI on 2
      chromosomes were identified by all 3 methods combined. Genes within each ROI were
      retrieved and used to identify pathways and genes that might contribute to
      performance in each subpopulation. These included, among others, candidate genes
      associated with skeletal muscle development, metabolism, and central nervous
      system development. This work improves our understanding of equine breed
      development, and provides breeders with a better understanding of how selective
      breeding impacts the performance of QH populations.

PMID- 30105050
TI  - Potential for Genetic Improvement of the Main Slaughter Yields in Common Carp
      With in vivo Morphological Predictors.
AB  - Common carp is a major aquaculture species worldwide, commonly sold alive but
      also as processed headless carcass or filets. However, recording of processing
      yields is impossible on live breeding candidates, and alternatives for genetic
      improvement are either sib selection based on slaughtered fish, or indirect
      selection on correlated traits recorded in vivo. Morphological predictors that
      can be measured on live fish and that correlate with real slaughter yields hence
      remain a possible alternative. To quantify the power of morphological predictors
      for genetic improvement of yields, we estimated genetic parameters of slaughter
      yields and various predictors in 3-year-old common carp reared communally under
      semi-intensive pond conditions. The experimental stock was established by a
      partial factorial design of 20 dams and 40 sires, and 1553 progenies were
      assigned to their parents using 12 microsatellites. Slaughter yields were highly
      heritable (h2 = 0.46 for headless carcass yield, 0.50 for filet yield) and
      strongly genetically correlated with each other (rg = 0.96). To create
      morphological predictors, external (phenotypes, 2D digitization) and internal
      measurements (ultrasound imagery) were recorded and combined by multiple linear
      regression to predict slaughter yields. The accuracy of the phenotypic prediction
      was high for headless carcass yield (R2 = 0.63) and intermediate for filet yield
      (R2 = 0.49). Interestingly, heritability of predicted slaughter yields (0.48
      0.63) was higher than that of the real yields to predict, and had high genetic
      correlations with the real yields (rg = 0.84-0.88). In addition, both predicted
      yields were highly phenotypically and genetically correlated with each other
      (0.95 for both), suggesting that using predicted headless carcass yield in a
      breeding program would be a good way to also improve filet yield. Besides, two
      individual predictors (P1 and P2) included in the prediction models and two
      simple internal measurements (E4 and E23) exhibited intermediate to high
      heritability estimates (h2 = 0.34 - 0.72) and significant genetic correlations to
      the slaughter yields (rg = |0.39 - 0.83|). The results show that there is a solid
      potential for genetic improvement of slaughter yields by selecting for predictor
      traits recorded on live breeding candidates of common carp.

PMID- 30105051
TI  - A Reduction in ADAM17 Expression Is Involved in the Protective Effect of the PPAR
      alpha Activator Fenofibrate on Pressure Overload-Induced Cardiac Hypertrophy.
AB  - The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist
      fenofibrate ameliorates cardiac hypertrophy; however, its mechanism of action has
      not been completely determined. Our previous study indicated that a disintegrin
      and metalloproteinase-17 (ADAM17) is required for angiotensin II-induced cardiac
      hypertrophy. This study aimed to determine whether ADAM17 is involved in the
      protective action of fenofibrate against cardiac hypertrophy. Abdominal artery
      constriction- (AAC-) induced hypertensive rats were used to observe the effects
      of fenofibrate on cardiac hypertrophy and ADAM17 expression. Primary
      cardiomyocytes were pretreated with fenofibrate (10 MUM) for 1 hour before being
      stimulated with angiotensin II (100 nM) for another 24 hours. Fenofibrate reduced
      the ratios of left ventricular weight to body weight (LVW/BW) and heart weight to
      body weight (HW/BW), left ventricular anterior wall thickness (LVAW), left
      ventricular posterior wall thickness (LVPW), and ADAM17 mRNA and protein levels
      in left ventricle in AAC-induced hypertensive rats. Similarly, in vitro
      experiments showed that fenofibrate significantly attenuated angiotensin II
      induced cardiac hypertrophy and diminished ADAM17 mRNA and protein levels in
      primary cardiomyocytes stimulated with angiotensin II. In summary, a reduction in
      ADAM17 expression is associated with the protective action of PPAR-alpha agonists
      against pressure overload-induced cardiac hypertrophy.

PMID- 30105049
TI  - Genome Wide Identification of Novel Long Non-coding RNAs and Their Potential
      Associations With Milk Proteins in Chinese Holstein Cows.
AB  - Long non-coding RNAs (lncRNAs) have emerged as a novel class of regulatory
      molecules involved in various biological processes. However, their role in milk
      performance is unknown. Here, whole transcriptome RNA sequencing was used to
      generate the lncRNA transcriptome profiles in mammary tissue samples from 6
      Chinese Holstein cows with 3 extremely high and 3 low milk protein percentage
      phenotypes. In this study, 6,450 lncRNA transcripts were identified through 5
      stringent steps and filtration by coding potential. In total, 31 lncRNAs and 18
      novel genes were identified to be differentially expressed in high milk protein
      samples (HP) relative to low milk protein samples (LP), respectively.
      Differentially expressed lncRNAs were selected to predict target genes through
      bioinformatics analysis, followed by the integration of differentially expressed
      mRNA data, gene function, gene ontology (GO) and pathway, genome wide association
      study (GWAS) and quantitative trait locus (QTL) information, as well as network
      analysis to further characterize potential interactions. Several lncRNAs were
      found (such as XLOC_059976) that could be used as candidate markers for milk
      protein content prediction. This is the first study to perform global expression
      profiling of lncRNAs and mRNAs related to milk protein traits in dairy cows.
      These results provide important information and insights into the synthesis of
      milk proteins, and potential targets for the future improvement of milk quality.

PMID- 30105052
TI  - Experience with Treating Lentigo Maligna with Definitive Radiotherapy.
AB  - Lentigo maligna (LM) is a form of melanoma in situ that occurs on exposed, sun
      damaged skin; LM can progress to invasive melanoma. Conventional surgical
      treatment is the preferred management option as it is usually a one-treatment
      episode and generates a histopathology report that records completion of
      excision. Some patients may not be surgical candidates due to comorbidities,
      patient preference, impact on function, and cosmesis or they have failed surgery
      with a positive margin. Other therapies, including radiotherapy (RT) and topical
      medicines, may then become appropriate. There is a currently accruing multi
      institutional randomized trial of imiquimod versus definitive RT for this
      population (NCT02394132). This review is about the experience from the centre
      that has generated the trial and enrolled the most patients to date. The purpose
      of the review is to pass on experience to other centers who may want to join the
      trial, especially to supplement the experience of local radiation oncologists.
      The review covers decisions that need to be made in RT planning and treatment and
      how to manage side effects and other common scenarios including LM in
      immunosuppressed patients and in poorly vascularised tissue, after surgery, of
      the eyelid and of mucous membrane (mouth and nose) that are in the radiation
      field.

PMID- 30105053
TI  - Role of the Mechanisms of Detection in the Increased Risk of Thyroid Cancer: A
      Retrospective Cohort Study in an HMO in Buenos Aires.
AB  - Background: Two hypotheses attempt to explain the increase of thyroid cancer (TC)
      incidence: overdetection by excessive diagnostic scrutiny and a true increase in
      new cases brought about by environmental factors. Changes in the mechanism of
      detection and the risk of incidentally diagnosed TC could result in an increase
      of TC incidence. Methods: Retrospective cohort study. We identified incident
      cases of TC from the pathological reports of patients in a HMO and review of
      clinical records. The results were analyzed in two periods: 2003-2007 and 2008
      2012. Incidence rates expressed per 100,000 person-years (with 95% CI) and
      relative risk of incidence rates of incidental and nonincidental TC were
      estimated. Results: The relative risk of incidentally detecting a thyroid cancer
      in 2008-2012 compared to 2003-2007 was 6.06 (95%CI 1.84-20.04). Clinical
      evaluations detected 31 (75.6%) cancers in the period 2003-2007 and 70 (51.8%)
      cancers in the period 2008-2012 (p<0.007). Although tumor median size was
      significantly lower in the period 2008-2012 (10 vs. 14 mm, p<0.03), tumors
      greater than 40 mm (4.3%) were only present in 2008-2012. The female/male ratio
      decreased between analyzed periods from 8 (3-21) to 4 (3-7). Conclusions: Our
      findings partially support the hypothesis of increased incidence due to
      overdetection but do not explain the changes in the increase of larger tumors and
      decrease in the female/male ratio, which could be secondary to the influence of
      unidentified environmental factors.

PMID- 30105054
TI  - Authenticity Detection of Black Rice by Near-Infrared Spectroscopy and Support
      Vector Data Description.
AB  - Black rice is an important rice species in Southeast Asia. It is a common
      phenomenon to pass low-priced black rice off as high-priced ones for economic
      benefit, especially in some remote towns. There is increasing need for the
      development of fast, easy-to-use, and low-cost analytical methods for
      authenticity detection. The feasibility to utilize near-infrared (NIR)
      spectroscopy and support vector data description (SVDD) for such a goal is
      explored. Principal component analysis (PCA) is used for exploratory analysis and
      feature extraction. Another two data description methods, i.e., k-nearest
      neighbor data description (KNNDD) and GAUSS method, are used as the reference. A
      total of 142 samples from three brands were collected for spectral analysis. Each
      time, the samples of a brand serve as the target class whereas other samples
      serve as the outlier class. Based on both the first two principal components
      (PCs) and original variables, three types of data descriptions were constructed.
      On average, the optimized SVDD model achieves acceptable performance, i.e., a
      specificity of 100% and a sensitivity of 94.2% on the independent test set with
      tight boundary. It indicates that SVDD combined with NIR is feasible and
      effective for authenticity detection of black rice.

PMID- 30105055
TI  - Emulsion Cross-Linking Technique for Human Fibroblast Encapsulation.
AB  - Microencapsulation with biodegradable polymers has potential application in drug
      and cell delivery systems and is currently used in probiotic delivery. In the
      present study, microcapsules of human fibroblast cells (CRL2522) were prepared by
      emulsion cross-linking technique. Tween 80 surfactant at a 2% concentration
      through phase inversion resulted in the most efficient and stable size,
      morphology, and the cells survival at least 50% on day 14. Emulsion cross-linking
      microcapsule preparation resulted in smaller and possibly more diverse particles
      that can be developed clinically to deliver encapsulated mammalian cells for
      future disease treatments.

PMID- 30105056
TI  - Patients' Knowledge of Artemisinin-Based Combination Therapy Treatment and Its
      Impact on Patient Adherence.
AB  - Despite increased support from government and other stakeholders for malaria
      control over the past decade, malaria burden remains high in many endemic
      countries, particularly in Sub-Saharan Africa. This study aimed to assess
      patients' knowledge of antimalarial treatment (ACT) and its association with
      patient adherence. A descriptive cross-sectional study design was employed in
      this study. Data were collected from April to May 2017. Both descriptive and
      inferential statistics in the form of frequencies, percentages, mean values,
      standard deviations, and Pearson's chi-square test were generated by use of
      Microsoft excel spreadsheet and IBM Statistical Package for Social Sciences
      (SPSS) version 23. The average age of the respondents surveyed for this study was
      42.27 +/- 11.09. Adherence level to ACT was 47%. The results showed that there
      was a significant association between respondents' knowledge of the efficacy of
      antimalarial medication (p = 0.003), benefits of completing antimalarial
      treatment course (p = 0.001), and consequences of not completing the doses of
      antimalarial medication prescribed (p = 0.002) and adherence to ACT. This study
      then recommends that improving patients' knowledge regarding the efficacy,
      benefits of completing ACT, and consequences of not completing ACT treatment may
      improve the likelihood of patients adhering fully to ACT.

PMID- 30105058
TI  - Vitamin D Status and Associated Factors in Neonates in a Resource Constrained
      Setting.
AB  - Vitamin D deficiency (VDD) is emerging as a serious public health problem
      globally; however due to lack of resources, vitamin D levels are not routinely
      measured among neonates. The study was conducted to determine vitamin D levels in
      neonates and factors associated with the same. A cross-sectional study was
      conducted among neonates admitted at neonatal ward of a tertiary care hospital.
      Means and proportions were calculated from summarized data in frequency tables.
      Chi square test was used to determine association between vitamin D and various
      associated factors such as sex, infant birth weight, gestation age, parity of the
      mother, maternal age, and HIV status of the mother. A total of 170 neonates were
      studied, out of which 80% had vitamin D deficiency. Neonates born to HIV-infected
      mothers were significantly less likely to have vitamin D deficiency (OR 0.21, 95%
      CI 0.06 - 0.77, p = 0.009). Subgroup analysis revealed the association to be
      stronger in terms neonates (p = 0.005). The association was not observed among
      preterm newborns. The prevalence of vitamin D deficiency in neonates was observed
      to be very high and needs more attention.

PMID- 30105057
TI  - Assessing the Influence of Water Management and Rainfall Seasonality on Water
      Quality and Intestinal Parasitism in Rural Northeastern Brazil.
AB  - Introduction: The drought in the Brazilian semiarid region has affected the
      quality of water. This study assessed the relationships between enteric
      parasitoses, water management, and water quality, correlating them with
      pluviometric seasonality. Methods: Cross-sectional surveys were carried out in
      four rural communities at the beginning of the dry season (n=151), at the end of
      the dry season (n=184), and in the rainy season (n=199), in order to collect
      sociodemographic data, human fecal samples, and samples of the water used for
      human consumption for physicochemical and microbiological analyses. In 2015,
      water filters were provided to 30 households under study. Results: There was an
      increasing trend in detection rates of commensal protozoa and the Entamoeba
      histolytica/Entamoeba dispar complex at the beginning of the rainy season, with
      detection rates of 6% in 2014 and 21.6% in 2016. Giardia intestinalis and Ascaris
      lumbricoides presented distinct temporal distributions, which peaked in 2015:
      20.1% and 30%, respectively. The proportion of inhabitants drinking inadequate
      water was 55% at the beginning of the dry season and 28.8% at the end of the dry
      season, reaching 70.9% at the beginning of the rainy season. The presence of
      filters reduced this proportion among those who received the hollow ceramic
      candle filter. Conclusions: Data suggest that the strategies to increase water
      supply in the Brazilian semiarid region can be ameliorated in order to improve
      the quality of drinking water.

PMID- 30105059
TI  - Formaldehyde Vapor Concentration in Electronic Cigarettes and Health Complaints
      of Electronic Cigarettes Smokers in Indonesia.
AB  - Electronic cigarettes regulation in Indonesia has not been set yet. In the last 4
      years the electronic cigarettes have been widely distributed and used in
      Indonesia. Electronic cigarettes contain nicotine, propylene glycol, glycerol,
      liquid flavors, etc. All ingredients produce vapor when heated. Vapor and
      particles from electronic cigarettes affect the human health. Formaldehyde is
      known as a product of propylene glycol and glycerol vapor degradation.
      Formaldehyde is one of the chemical agents categorized as carcinogen. The aim of
      the research was to analyze the identification of formaldehyde vapor
      concentration and health complaint of electronic cigarettes smoker. The research
      was conducted in Surabaya city, Indonesia, from October 2015 to December 2016.
      The research used cross-sectional approach. Sample was obtained by purposive
      sampling that fulfilled samples inclusion criteria. The variables were the onset
      of smoking electronic cigarettes, smoking frequency of electronic cigarettes,
      formaldehyde vapor concentration, cotinine urine, and health complaint of
      electronic cigarettes smoker. The result showed that formaldehyde concentration
      in six vapors varied while cotinine urine mostly was positive. It is suggested to
      educate people about hazard of electronic cigarettes and to conduct further
      research to identify chemical agent in electronic cigarettes.

PMID- 30105060
TI  - Effects of Modified Zhisou Powder on Airway Mucus Production in Chronic
      Obstructive Pulmonary Disease Model Rats with Cold-Dryness Syndrome.
AB  - Objective. In China, the Chinese medicine formula modified zhisou powder (MZP) is
      commonly used to treat COPD with cold-dryness syndrome (CDSCOPD) to relieve cough
      and sputum. However, the underlying mechanisms of MZP on treating CDSCOPD remain
      to be elucidated. Methods. COPD and CDSCOPD rat models were established; MZP was
      given to CDSCOPD rats in the last 7 days of the 97-day model establishment. Then
      the rats were subjected to lung function measurement. Pathological changes in
      lungs were observed through paraffin section and H&E staining. The mRNA and
      protein levels of AQP1, 4, and 5 and Muc5AC and Muc5B in lung were determined by
      quantitative RT-PCR and western blotting. NE levels was determined by ELISA.
      Results. The impaired lung functions were observed in rats exposed to cigarette
      smoke. Among all parameters evaluating lung functions, only tidal volume
      demonstrates a further decrease in CDSCOPD when compared with COPD, indicating
      further impaired pulmonary ventilation functions upon cold-dryness stimulation.
      The intervention of MZP effectively improved lung functions parameters, prevented
      the inflammations, and eliminated the increases of AQP4 and 5 and the decrease of
      Muc5AC in lung. Conclusion. MZP probably improves pulmonary functions in CDSCOPD
      through inhibiting lung inflammation, increasing expressions of AQPs, and
      decreasing Muc5AC expression in lung.

PMID- 30105061
TI  - Laser Speckle Imaging of Sensitized Acupoints.
AB  - Acupoints microcirculatory dynamics vary depending on the body's health status.
      However, the functional changes observed during acupoint sensitization, that is,
      the disease-induced change from a "silenced" to an "activated" status, remain
      elusive. In this study, the microcirculatory changes at acupoints during
      sensitization were characterized. Thirty SD rats were randomly divided into five
      groups: normal control group (N), sham osteoarthritis group (S), light
      osteoarthritis group (A), mild osteoarthritis group (B), and heavy osteoarthritis
      group (C). The obtained results showed that the blood perfusion levels at the
      acupoints Yanglingquan (GB34), Zusanli (ST36), and Heding (EX-LE2) in groups A,
      B, and C were higher than those in groups N and S on days 14, 21, and 28 (p <
      0.01 or p < 0.05). A significant difference in the blood perfusion was also
      observed at the acupoint Weizhong (BL40) in groups B and C on days 21 and 28 (p <
      0.01). In addition, remarkable differences in the level of blood perfusion at the
      GB34, ST36, and EX-LE2 acupoints were observed on day 28 (p < 0.01 or p < 0.05)
      among groups A, B, and C. No marked differences in blood perfusion levels were
      observed at the nonacupoint site among all groups. In conclusion, acupoint
      sensitization is associated with an increase in the level of local blood
      perfusion at specific acupoints, and this increase is positively correlated with
      the severity of the disease. The functional changes in microcirculation at
      acupoints during sensitization reflect the different physiological and
      pathological conditions imposed by the disease.

PMID- 30105062
TI  - Comparative Studies of Different Extracts from Eucommia ulmoides Oliv. against
      Rheumatoid Arthritis in CIA Rats.
AB  - To compare efficacy of different extracts from Eucommia ulmoides Oliv. with both
      immune inflammation and joint destruction in collagen induced arthritis (CIA) rat
      model. Rats were divided into normal group (Nor), control group (CIA), TG group
      (treated with tripterygium glycoside), E70 group (treated with 70% ethanol
      extract from Eucommia ulmoides Oliv.), EA group (treated with ethyl acetate
      fraction from E70), and EN group (treated with n-butyl alcohol fraction from
      E70). All extracts from Eucommia ulmoides Oliv. could significantly inhibit ankle
      swelling, pathological manifestations, and cytokine levels in serum and spleen,
      by using foot volume measurement, H&E staining, ELISA, and RT-QPCR methods,
      respectively. All extracts could significantly inhibit rough joint surface and
      marginal osteophytes, improve RANKL/OPG ratio, and decrease MMP-9 expression, by
      using micro-CT and immunohistochemical staining. The activation of IKK/NF-kappaB
      signaling pathway was also inhibited by all extracts. In addition, ethyl acetate
      fraction from E70 presented better effect on RANKL/OPG system. This study
      identified effective extracts from Eucommia ulmoides Oliv. relieving immune
      inflammation and maintaining structural integrity of joints in CIA rats.

PMID- 30105063
TI  - Antiulcer Effect of Honey in Nonsteroidal Anti-Inflammatory Drugs Induced Gastric
      Ulcer Model in Rats: A Systematic Review.
AB  - Background: Peptic ulcer is a basic term for ulcers on the lower oesophagus,
      stomach, or jejunum. The specific term for ulcer in the stomach is gastric ulcer.
      The extensive use of honey around the globe helps researchers to study the
      usefulness of honey. Many studies had already been conducted and proved the
      effectiveness of honey in treating gastric ulcer. Methods: A systematic review of
      the literature was conducted to identify relevant studies on honey used as an
      alternative treatment of gastric ulcer cause by NSAIDs. A comprehensive search
      was conducted in Medline, SCOPUS, and Ebscohost. The main criteria used were
      articles published in English and using NSAIDs-induced gastric ulcer in rat's
      model and those reporting the effectiveness of honey. Results: Articles published
      between 2001 and 2014 were identified to be relevant in studies related to the
      inclusion criteria. The literature search found 30 potential and closely related
      articles in this review, but only 5 articles were taken which meet the criteria
      needed to be fulfilled. Conclusions: All studies in this review reported the
      efficacy of honey for gastric ulcer based on its antioxidant and cytoprotective
      activities. Most of the studies conducted used different types of honey at
      various doses on rats. Future studies should be conducted to identify the
      appropriate dose for humans to achieve similar gastroprotective effects.

PMID- 30105064
TI  - Subinhibitory Concentrations of Prim-O-Glucosylcimifugin Decrease the Expression
      of Alpha-Hemolysin in Staphylococcus aureus (USA300).
AB  - Staphylococcus aureus (S. aureus), an important opportunistic pathogen in human
      and animal, causes a series of diseases in the impairing of immunity of host and
      even then death. Alpha-hemolysin (Hla), a primary virulence factor, plays a major
      role in the pathogenic progress of S. aureus, especially in pneumonia. Prim-O
      glucosylcimifugin (POG), a nature chromone compound, is an active ingredient in
      many Chinese Medicines. In this study, POG investigated the inhibitory effect of
      the secretion of Hla in S. aureus strain USA300 at the subinhibitory
      concentrations. The hemolysis assays and western blotting assays showed that POG
      can decrease the production of Hla in the USA300 growth cell cultures in a dose
      dependent manner. The results of RT-PCR revealed that reduction of Hla was
      related to inhibit the transcription of hla and RNAIII. In the cells experiment,
      POG was proved to protect A549 cells from Hla-medicated injury. In conclusion,
      POG was shown the capacity of decreased the production of S. aureus Hla. POG can
      be developed as a candidate agent to treat S. aureus infections against Hla.

PMID- 30105065
TI  - Neuronal Specificity of Acupuncture in Alzheimer's Disease and Mild Cognitive
      Impairment Patients: A Functional MRI Study.
AB  - Although acupuncture is considered to be effective and safe for Alzheimer's
      disease (AD) and mild cognitive impairment (MCI), the mechanism underlying its
      therapeutic effect is still unknown. Most studies clarifying the neuronal pathway
      produced by acupuncture were still applied to healthy subjects with limited
      single acupuncture point stimulation, which was inconsistency with clinical
      practice. Thus, in our present study, we investigate the differences between
      brain activity changes in AD and MCI patients caused by multi-acupuncture point
      Siguan (four gates), in order to provide visualized evidence for neuronal
      specificity of clinical acupuncture. Forty-nine subjects were recruited,
      including 21 AD patients, 14 MCI patients, and 14 healthy controls (HC). AD and
      MCI patients were randomly divided into two groups, respectively: real
      acupuncture point group (14 AD and 8 MCI) and sham acupuncture point group (7 AD
      and 6 MCI). We adopted a 16-minute, single-block, experimental design for
      acquiring functional MRI images. We found, in AD and MCI patients, Siguan (four
      gates) elicited extensive activations and deactivations in cognitive-related
      areas, visual-related areas, the sensorimotor-related area, basal ganglia, and
      cerebellum. Compared with HC, AD and MCI patients showed similar activations in
      cognitive-related brain areas (inferior frontal gyrus, supramarginal gyrus, and
      rolandic operculum) as well as deactivations in cognitive-related areas, visual
      related areas, basal ganglia, and cerebellum, which were not found in HC.
      Compared with sham acupuncture points, real acupuncture points produced more
      specific brain changes with both activated and deactivated brain activities in AD
      and MCI. The preliminary results in our study verified the objective evidence for
      neuronal specificity of acupuncture in AD and MCI patients.

PMID- 30105066
TI  - Comparative Efficacy of Chinese Herbal Injections for Treating Acute Exacerbation
      of Chronic Obstructive Pulmonary Disease: A Bayesian Network Meta-Analysis of
      Randomized Controlled Trials.
AB  - Introduction: Acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD) imposes a huge economic burden on healthcare systems worldwide. Chinese
      herbal injections (CHIs) are widely used to treat AECOPD. In this study, we
      examined the efficacy of CHIs in the treatment of AECOPD using a network meta
      analysis (NMA). Methods: Literature search was conducted from electronic
      databases of randomized controlled trials (RCTs) on CHIs plus Western medicine
      (WM) versus WM. WinBUGS 1.4.3 and STATA 12.0 were adopted to compute calculations
      and prepare graphs, respectively. Results: We included 155 RCTs with 13,218
      patients. The results revealed that Danhong injection (DH) + WM had the greatest
      therapeutic potential in terms of rate of clinical efficacy (RCE). In addition,
      in comprehensively improving RCE and FEV1%, and RCE and C-reactive protein,
      Huangqi injection (HQ) +WM was associated with preferable effects. Similarly,
      Xixinnao injection + WM, Reduning injection (RDN) +WM, and HQ+WM had a favorable
      effect on RCE and PaO2. The effect of RDN+WM was favorable in all outcomes except
      RCE. The safety of CHIs needs to be further assessed. Conclusions: Based on this
      NMA, DH+WM, HQ+WM, and RDN+WM were potential optimal therapies in AECOPD and
      their safety should be strictly monitored.

PMID- 30105067
TI  - Abyssinone V-4' Methyl Ether Isolated from Erythrina droogmansiana (Leguminosae)
      Inhibits Cell Growth and Mammary Glands Hyperplasia Induced in Swiss Mice by the
      7,12-Dimethylbenz(a)anthracene.
AB  - There is a long standing interest in the identification of medicinal plants and
      derived natural products for developing cancer therapeutics. The present study
      was designed to evaluate the in vitro and in vivo antiproliferative effects of
      Abyssinone V-4' methyl ether (AVME) on breast tissue of mice. The cytotoxicity of
      AVME was evaluated using MTT assay in four cancer cell lines (DU145, PC3, HepG2,
      and MCF-7). Further, a protective effect of AVME was evaluated on 7,12
      dimethylbenz(a)anthracene- (DMBA-) induced breast tumor in Swiss mice. Incidence,
      burden, volume, and histological analysis of mammary tumors were measured. As a
      result, AVME inhibits DU145, PC3, HepG2, and MCF-7 cells growth. In vivo, no
      tumor was detected in mice from the normal group as compared to those of DMBA
      group. Moreover, AVME inhibits the DMBA-induced mammary glands hyperplasia in
      mice at the dose of 10 mg/kg, evidenced by a decrease of tumor incidence, tumor
      weight, and volume as well as a protective effect against the lobular alveolar
      hyperplasia. Taken all together, these results suggest that Abyssinone V-4'
      methyl ether is endowed with antitumor properties and could be a source of
      traditional medicine which deserves to be more elucidated and explored in the
      foreseeable future.

PMID- 30105068
TI  - Annona muricata Leaf Extract Triggered Intrinsic Apoptotic Pathway to Attenuate
      Cancerous Features of Triple Negative Breast Cancer MDA-MB-231 Cells.
AB  - Annona muricata L., known as graviola, is an evergreen plant of the tropical
      regions and is a rich source of natural products. Graviola has various biological
      activities, and it is best known for its anticancer activity. This study aimed to
      investigate the effects of crude graviola extract in vitro on breast cancer
      cells; in particular, we aimed to identify an agent against triple negative
      breast cancer (TNBC). We used the TNBC MDA-MB-231 cell line as the experimental
      model and the ER(+) non-TNBC MCF-7 breast cancer cell line as the control. We
      identified annonaceous acetogenins, including annonacin isomers, characteristic
      to this plant by using liquid chromatography tandem mass spectrometry (LC/MS/MS).
      We observed a significant decrease in the cell viability in both cell lines
      within 48 h, whereas impaired cell motility and invasiveness were observed only
      in the MDA-MB-231 cell line. While the MCF-7 cells showed an ER-dependent
      mechanism of apoptosis, the apoptosis of MDA-MB-231 cells was governed by an
      intrinsic apoptotic pathway triggered by graviola leaf extract (GLE).

PMID- 30105070
TI  - Natural Products as a Source for New Leads in Cancer Research and Treatment.

PMID- 30105069
TI  - Gypenosides Altered Hepatic Bile Acids Homeostasis in Mice Treated with High Fat
      Diet.
AB  - Gypenosides extracted from Gynostemma pentaphyllum (Thunb.) Makino have
      significant role in reducing serum lipid level and treating fatty liver diseases,
      however, without clear mechanism. As gypenosides share the similar core
      structures with bile acids (the endogenous ligands of nuclear receptor FXR), we
      hypothesize that gypenosides may improve hypercholesterolemia via FXR-mediated
      bile acids signaling. The present study was designed to validate the role of
      gypenosides in reducing levels of serum total cholesterol (TC) and low density
      lipoprotein cholesterol (LDL-C), as well as in regulating bile acids homeostasis
      and related gene expression levels. The C57BL/6 male mice were divided into four
      groups. Mice in groups ND and HFD were fed with normal diet and high fat diet for
      38 weeks, respectively. In groups HFD+GP and HFD+ST, mice were fed with high fat
      diet for 38 weeks and treated with gypenosides and simvastatin (positive control)
      from weeks 16 to 38, respectively. Serum TC and LDL-C levels were assayed by
      commercially available kits. Expression levels of genes were tested by the
      quantitative real-time PCR. The LC-MS/MS was applied to quantify major bile acids
      in mice livers. Our results showed that gypenosides significantly decreased serum
      TC and LDL-C levels. The gene expression level of Shp was downregulated while the
      levels of Cyp7a1, Cyp8b1, Fxr, Lrh1, Jnk1/2, and Erk1/2 were upregulated by
      gypenosides. Indicated by LC-MS/MS technology, gypenosides increased the hepatic
      levels of several free bile acids and most taurine-conjugated bile acids while
      decreasing glycine-conjugated bile acids levels. In addition, gypenosides
      decreased the CA/CDCA ratio. Gypenosides may improve the abnormal lipid profile
      of HFD-fed mice via two pathways: (1) enhancing the bile acids biosynthesis from
      cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to
      cholesterol absorption.

PMID- 30105071
TI  - Involvement of Flavonoids from the Leaves of Carya cathayensis Sarg. in Sirtuin 1
      Expression in HUVEC Senescence.
AB  - Atherosclerosis is the commonest cause of death in the world and one of the most
      important processes that occurs with increasing age because it is accompanied by
      progressive endothelial dysfunction. Recent studies demonstrated that Sirtuin 1
      (SIRT1) might potentially affect cell senescence. However, the effect of SIRT1 on
      the regulation of human umbilical vein endothelial cell (HUVEC) senescence with
      total flavonoids (TFs) has not been addressed previously. This study investigated
      how SIRT1 functions in the process of HUVEC senescence when TFs are present and
      identified the potential molecular mechanisms involved. Using a model of HUVEC
      senescence induced by angiotensin II, TFs pretreatment reduced the percentage of
      senescence-associated beta-galactosidase (SA-beta-gal) cells and p53 mRNA
      expression. The level of SIRT1 protein and E2F1 decreased during HUVEC senescence
      and could be partially recovered when cells were coincubated with TFs, while the
      levels of proteins p53 and p21 increased during cell senescence and diminished in
      response to the TFs treatment. When coincubated with 20 mM nicotinamide, the
      results with SA-beta-gal-positive cells and the expression of SIRT1, E2F1, p53,
      and p21 were contrary to that obtained with only TFs pretreatment. The data
      indicate that the TFs exert their effect on HUVEC senescence through SIRT1.

PMID- 30105072
TI  - Electroacupuncture Could Influence the Expression of IL-1beta and NLRP3
      Inflammasome in Hippocampus of Alzheimer's Disease Animal Model.
AB  - Background: Effective therapies for Alzheimer's disease (AD) are still being
      explored. Electroacupuncture with traditional Chinese medicine theory may improve
      spatial learning and memory abilities and glucose metabolism rates in an animal
      model of AD. However, the mechanism of electroacupuncture in intervention of AD
      is still unclear. According to recent studies of AD mechanisms, the NLRP3
      inflammasome regulated the expression of IL-1beta in the brain which may mediate
      AD related processes. Therefore, in our study, we intend to explore the possible
      relation between electroacupuncture and the expression of NLRP 3 inflammasome in
      the hippocampus of an AD animal model. Method: In this study, 7.5-month-old male
      senescence-accelerated mouse prone 8 (SAMP8) mice were used as an AD animal
      model, which were randomly divided into two groups: Alzheimer's disease model
      group (AD group) and electroacupuncture group (EA group). In the control
      paradigm, 7.5-month-old male SAMR1 mice were used as the normal control group (N
      group). DU20, DU26, and EX-HN3 were selected as the acupuncture points, and after
      a 15-day treatment of electroacupuncture, we used immunohistochemistry and
      Western blotting to examine the expression of IL-1beta and NLRP3, ASC, and
      Caspase-1 in the hippocampus of the AD animal model. Results: Compared with N
      group, IL-1beta, NLRP3, ASC, and Caspase-1 positive cells in AD group were
      increased, and the relative expression of all above proteins significantly
      increased (P < 0.01). Compared with AD group, the expression of IL-1beta, NLRP3,
      ASC, and Caspase-1 in EA group was significantly decreased (P < 0.01).
      Conclusion: Electroacupuncture treatment could inhibit the inflammation reaction
      in the hippocampus of SAMP8 mice. What is more, the possible mechanism of
      electroacupuncture reduced the expression of IL-1beta and NLRP3 inflammasome
      relative protein.

PMID- 30105073
TI  - Ethnobotanical Study of Medicinal Plants Used to Treat Human Diseases in Berbere
      District, Bale Zone of Oromia Regional State, South East Ethiopia.
AB  - This paper reports an ethnobotanical study that focused on the traditional
      medicinal plants used by local communities to treat human diseases.
      Ethnobotanical study of medicinal plants was carried out from June 25 to
      September 5, 2015, in Berbere district of Oromia region, Ethiopia. The study
      focused on documentation of medicinal plants used to treat various human diseases
      in the study area. Ethnobotanical data were collected using semistructured
      interviews, group discussion, guided field walks, and observations with
      participants. Preference ranking, paired comparison, direct matrix ranking, and
      informant consensus factors (ICF) were used to analyze the importance of some
      plant species. A total of 70 medicinal plants, distributed in 56 genera and 46
      families, were collected and identified. Plant family with the highest medicinal
      plants in the study area used for various diseases treatment was Euphorbiaceae
      (11.4%). The result of growth form analysis showed that shrubs constituted the
      highest proportion of medicinal plants (48.6%). Roots, 43 (44.8%), were the most
      frequently utilized plant parts for preparation of traditional herbal medicines.
      Crushing was a widely used mode of preparation of traditional remedies where oral
      administration (37.5%) was the dominant route. The highest informants consensus
      factor (ICF) values were linked to gonorrhea and syphilis disease (0.95); the
      lowest was linked with external parasites and wound (0.69). Local people in the
      study area possess traditional knowledge of medicinal plants to treat various
      human ailments; however, agricultural expansion and disinterest of young
      generation became the major threat to medicinal plants. It is, therefore,
      necessary to preserve this indigenous knowledge on traditional medicines by
      proper documentation, identification of plant species used, and herbal
      preparation. To save medicinal plants from further loss, involving local
      communities in cultivation of the most utilized medicinal plants is recommended.

PMID- 30105074
TI  - Probabilistic Risk Assessment of Inorganic Arsenic via Consumption of Herbs
      Collected in Thailand.
AB  - Total and inorganic arsenic contents in ten commonly consumed Thai herbs, namely,
      bird's eye chili, cayenne pepper, celery, garlic, holy basil, kitchen mint,
      lemongrass, pepper, shallot, and sweet basil, were determined using atomic
      absorption spectrometry coupled with a hydride generation system (HG-AAS). Total
      arsenic contents in fresh herbs and lyophilized herbs ranged from 3.39 to 119
      ng/g wet weight (wet wt) and from 41.0 to 156 ng/g dry weight (dry wt),
      respectively. Inorganic arsenic contents in fresh herbs and lyophilized herbs
      ranged from 2.09 to 26.9 ng/g (wet wt) and from 23.5 to 55.5 ng/g (dry wt),
      respectively. Percentages of inorganic arsenic to total arsenic in herbs ranged
      from 22.7 to 62.0%. High percentages of inorganic arsenic to total arsenic were
      found in celery, lemongrass and sweet basil. Total arsenic contents in the
      studied herbs were lower than the maximum limits of Thai and Chinese regulatory
      standards, set at 2,000 ng/g in foods (excluding aquatic animals and seafood) and
      500 ng/g in fresh vegetables, respectively. Total and inorganic arsenic contents
      in the studied herbs were comparable to or lower than the levels found in other
      studies in the EU and China. Lifetime average daily dose (LADD) and cancer risk
      (CR) of inorganic arsenic exposure to commonly consumed herbs were evaluated
      using probabilistic risk assessment (PRA) by @RISK software version 6.0 of
      Palisade cooperation. All calculated LADD and CR values from all herbs did not
      exceed the acceptable levels. It can be concluded that there were very low cancer
      risks of inorganic arsenic exposure from the consumption of the studied herbs.

PMID- 30105075
TI  - Identification of Digestive Enzyme Inhibitors from Ludwigia octovalvis (Jacq.)
      P.H.Raven.
AB  - Current antiobesity and antidiabetic tools have been insufficient to curb these
      diseases and frequently cause side effects; therefore, new pancreatic lipase and
      alpha-glucosidase inhibitors could be excellent aids for the prevention and
      treatment of these diseases. The aim of this study was to identify, quantify, and
      characterize the chemical compounds with the highest degree of inhibitory
      activity of these enzymes, contained in a Ludwigia octovalvis hydroalcoholic
      extract. Chemical purification was performed by liquid-liquid separation and
      column chromatography. Inhibitory activities were measured in vitro, employing
      acarbose, orlistat, and a Camellia sinensis hydroalcoholic extract as references.
      For structural elucidation, Nuclear Magnetic Resonance was carried out, and High
      Performance Liquid Chromatography was used to quantify the compounds. For alpha
      glucosidases, L. octovalvis hydroalcoholic extract and its ethyl acetate fraction
      showed half-maximal Inhibitory Concentration (IC50) values of 700 and 250 MUg/mL,
      for lipase, 480 and 718 MUg/mL, while C. sinensis showed 260 and 587 MUg/mL. The
      most active compounds were identified as ethyl gallate (1, IC50 832 MUM) and
      gallic acid (2, IC50 969 MUM); both displayed competitive inhibition of alpha
      glucosidases and isoorientin (3, IC50 201 MUM), which displayed uncompetitive
      inhibition of lipase. These data could be useful in the development of a novel
      phytopharmaceutical drug.

PMID- 30105076
TI  - Different Harmonic Characteristics Were Found at Each Location on TCM Radial
      Pulse Diagnosis by Spectrum Analysis.
AB  - Purpose: This study aimed to clarify whether it is appropriate to choose any
      measurement location for pulse diagnosis research. Methods: A total of 37
      subjects were recruited and measured for pulse pressure waves at 18 locations (9
      per hand of "three positions and nine indicators"). These data were Fourier
      transformed to the frequency spectrum, and the harmonics of C0-C10 of each
      location were obtained. Box plots of the harmonics were generated using SPSS
      v.22.0 and R v.3.4.1. Data were compared with multivariate analysis of variance
      (MANOVA) with a randomized block design. Results: The results showed that certain
      harmonics were different at different positions and different indicators; the
      harmonics of the same indicator at different positions (except for C8 and C10)
      and those of different indicators for the same position (except for C4 and C5)
      were significantly different (p<0.05). Conclusions: In future researches of pulse
      diagnosis, due to the significant differences between positions and indicators,
      it is recommended that the measurement position should be carefully chosen
      instead of choosing any measurement location to ensure the integrity of the
      acquired information for further analyzing physiological or pathological status.

PMID- 30105077
TI  - A Comprehensive Review on Phytochemistry and Pharmacological Activities of
      Clinacanthus nutans (Burm.f.) Lindau.
AB  - Clinacanthus nutans (Burm.f.) Lindau (Acanthaceae), commonly known as Sabah snake
      grass, is a vegetable and a well-known herb that is considered an alternative
      medicine for insect bites, skin rashes, herpes infection, inflammation, and
      cancer and for health benefits. Current review aims to provide a well-tabulated
      repository of the phytochemical screening, identification and quantification, and
      the pharmacological information of C. nutans according to the experimental design
      and the plant preparation methods which make it outstanding compared to existing
      reviews. This review has documented valuable data obtained from all accessible
      library databases and electronic searches. For the first time we analyzed the
      presence of flavonoids, triterpenoids, steroids, phytosterols, and glycosides in
      C. nutans based on the results from phytochemical screening which are then
      further confirmed by conventional phytochemical isolation methods and advanced
      spectroscopic techniques. Phytochemical quantification further illustrated that
      C. nutans is a good source of phenolics and flavonoids. Pharmacological studies
      on C. nutans revealed that its polar extract could be a promising anti
      inflammation, antiviral, anticancer, immune and neuromodulating, and plasmid DNA
      protective agent; that its semipolar extract could be a promising antiviral,
      anticancer, and wound healing agent; and that its nonpolar extract could be an
      excellent anticancer agent.

PMID- 30105078
TI  - Chaihu-Shugan-San Decoction Modulates Intestinal Microbe Dysbiosis and Alleviates
      Chronic Metabolic Inflammation in NAFLD Rats via the NLRP3 Inflammasome Pathway.
AB  - We evaluate the effects of the Chaihu-Shugan-San decoction on intestinal microbe
      dysbiosis and chronic metabolic inflammation via the NLRP3 pathway in NAFLD rats
      that were fed a high-fat diet. Twenty-four SD rats (male, six weeks old, 200 +/-
      20 g) were randomly divided into three groups: normal control group (NC group),
      high-fat diet-fed group (HFD group), and Chaihu-Shugan-San decoction intervention
      group (CH group). The NC group rats were given standard feed, the HFD group rats
      were all fed a high-fat diet (83% standard feed + 10% lard oil + 5% sucrose +
      1.5% cholesterol + 0.5% cholate), and the CH group rats were given a HFD plus
      Chaihu-Shugan-San at 9.6 g*kg-1*d-1. Body composition, serum and liver lipids,
      inflammatory markers, intestinal microbial population, and the NLRP3 pathway
      associated protein were assessed. The results showed that Chaihu-Shugan-San
      decoction significantly reduced body weight and total fat mass and the levels of
      serum LPS, TG, TNF-alpha, IL-1beta, and IL-18, as well as liver TC, TG, TNF
      alpha, IL-1beta, and IL-18 (P < 0.05). The abundance of Enterobacteriaceae
      (0.375% versus 0.064%, P < 0.05), Staphylococcaceae families (0.049% versus
      0.016%, P < 0.05) and Veillonella genus (0.096% versus 0.009%, P < 0.01)
      significantly decreased, whereas the abundance of Anaeroplasma genus (0.0005%
      versus 0.0178%, P < 0.01) significantly increased. The expression levels of
      NLRP3, ASC, and Caspase-1 were changed significantly (P < 0.05). In summary, the
      Chaihu-Shugan-San decoction modulated intestinal microbe dysbiosis, reduced fat
      accumulation, and alleviated inflammatory factor expression, which are all
      processes related to the NLRP3 inflammasome pathway in NAFLD rats.

PMID- 30105079
TI  - Microbial Diversity of Chronic Wound and Successful Management of Traditional
      Chinese Medicine.
AB  - Chronic ulcer, including diabetic ulcer, varicose ulcer, and pressure ulcer,
      negatively affects patients' quality of life. As microbiology plays an important
      role in the mechanism of pathology for chronic wound healing, this study
      concentrates on microecology environment of the wound and how Traditional Chinese
      Medicine (TCM) regulates wound bacteria. Method. The study took wound samples
      from 35 patients and analyzed bacteria variation before and after TCM treatment
      by 16s rRNA sequencing. All samples were evaluated from aspects of alpha
      diversity, beta-diversity, and Simpson's Diversity index. Result. After total DNA
      extraction, PCR, and 16S rRNA sequencing of wound bacteria from 35 individuals,
      it was discovered that younger patients with shorter course of disease have a
      higher microbial diversity and were easier to recover from ulcers. Additionally,
      gender also played a vital role in wound healing, and a significant microbial
      diversity existed between male and female patients. Conclusion. Patients with
      chronic ulcers achieved a positive effect after TCM treatment (skin-producing
      ointment). Mechanistically, TCM helped promote wound healing by regulating the
      wound microbiota.

PMID- 30105080
TI  - Ethanol Extract of Lycopus lucidus Turcz. ex Benth Inhibits Metastasis by
      Downregulation of Runx-2 in Mouse Colon Cancer Cells.
AB  - Lycopus lucidus Turcz. ex Benth (LT) has been broadly used as a traditional
      medicinal herb in Asia including Korea, China, and Japan due to its noted ability
      to promote blood circulation and remove blood stasis. However, its anticancer
      mechanism is not understood. This study aims to elucidate the effects of ethanol
      extracts of LT (ELT) relative to the role of Runt-related transcription factor-
      (Runx-) 2 in the invasive and metastatic potentials of mouse colon cancer to
      determine the underlying mechanisms involved. ELT was evaluated for the
      antimetastasis activity using CT-26 colon cancer using wound healing, transwell
      matrigel, and western blot analysis. We used Runx-2-specific siRNA to further
      determine the relationship between Runx-2 and matrix metalloprotease- (MMP-) 9 in
      the migration and invasion of CT-26 cells. Runx-2 was first demonstrated to be a
      transcription factor that plays a remarkable role in diverse biological processes
      of chondrocytes and osteoblasts, but recently, Runx-2 has been reported to be
      associated with the progression of certain human cancers. ELT was not altered in
      its effects on growth inhibition. However, ELT significantly inhibited wound
      closure and cell invasion in a dose-dependent manner. ELT decreased the
      metastasis by regulating the activity of MMP-9 and Runx-2 at the translational
      levels. Our results demonstrate that ELT decreases metastasis by inhibiting the
      Runx-2-MMP-9 axis. We suggest that it can be used as a novel agent in therapeutic
      strategies for combating colon cancer.

PMID- 30105081
TI  - Effect of Wine Wastes Extracts on the Viability and Biofilm Formation of
      Pseudomonas aeruginosa and Staphylococcus aureus Strains.
AB  - In this work, we intended to inhibit the biofilm synthesis and the metabolism of
      Gram-positive and Gram-negative bacteria using two highly available wastes (stem
      and marc) obtained after the manufacturing of Torrontes wine at Cafayate,
      Argentina. Wine wastes contain a significant amount of bioactive compounds,
      mainly phenolic compounds, which makes them a potential source of compounds with
      beneficial properties to human health, as they could inhibit the virulence of
      pathogenic bacteria or protect the tissue against oxidative stress. Marc and stem
      extracts of Torrontes wine were evaluated for their ability to inhibit the
      metabolism and biofilm production of Pseudomonas aeruginosa and Staphylococcus
      aureus strains. The phytochemical composition and antioxidant activity of these
      extracts were also determined. The methanol and ethyl acetate extracts, which
      contained the highest amount of total polyphenolic, exhibited the highest
      scavenging capacity of ABTS and nitric oxide and the strongest Fe3+ reducing
      power and exhibited the highest level of inhibition of the biofilm formation and
      of the metabolic activity in bacterial biofilm. We also noticed a positive
      correlation between phenolic compounds content, the antioxidant activity, and the
      anti-biofilm capacity of the winemaking wastes. These results display the
      potentiality of wine wastes to prevent or reduce the formation of biofilm.
      Moreover, their abundance makes them an attractive and affordable source of
      antibiofilm and antioxidant agents.

PMID- 30105082
TI  - Corrigendum to "Pharmacological Basis for Use of Selaginella moellendorffii in
      Gouty Arthritis: Antihyperuricemic, Anti-Inflammatory, and Xanthine Oxidase
      Inhibition".
AB  - [This corrects the article DOI: 10.1155/2017/2103254.].

PMID- 30105084
TI  - Stability Analysis of Delayed Immune Response BCG Infection in Bladder Cancer
      Treatment Model by Stochastic Perturbations.
AB  - We present a revised mathematical model of the immune response to Bacillus
      Calmette-Guerin (BCG) treatment of bladder cancer, optimized according to
      biological and clinical data accumulated during the last decade. The improved
      model accounts for cytotoxic T lymphocyte differentiation as an integral element
      of the delayed immune response, as well as the logistic growth terms for cancer
      cell proliferation. Three equilibria are demonstrated for the proposed model,
      which is assumed to be influenced by white noise stochastic perturbations that
      are directly proportional to the system state deviation from an equilibrium.
      Stability conditions for all equilibria are analyzed using the Kolmanovskii
      Shaikhet general method of Lyapunov functionals construction.

PMID- 30105085
TI  - Hepatic sarcoidosis with atypical radiological manifestations: A case report.
AB  - Sarcoidosis is a multisystemic inflammatory disease of unknown origin
      characterized by the formation of noncaseating granulomas and accumulation of
      inflammatory cells. Sarcoidosis most commonly affects the lungs and lymphoid
      system. However, the liver can also be involved in 50%-65% of cases. On magnetic
      resonance imaging, sarcoidosis lesions usually present as hypointense lesions on
      all sequences. However, we present a rare case of nodular liver sarcoidosis
      presenting with T2 hyperintense lesions. In addition, while most cases of hepatic
      nodular sarcoidosis present with multiple small hepatic nodules, liver masses of
      our case are larger than usual. Moreover, this case suggested that when intact
      vascular structures penetrating liver nodular lesions are observed as in the
      current case, liver sarcoidosis can be included in a list of differential
      diagnosis.

PMID- 30105083
TI  - A Practical Guide to Analyzing Time-Varying Associations between Physical
      Activity and Affect Using Multilevel Modeling.
AB  - There is growing interest in within-person associations of objectively measured
      physical and physiological variables with psychological states in daily life.
      Here we provide a practical guide with SAS code of multilevel modeling for
      analyzing physical activity data obtained by accelerometer and self-report data
      from intensive and repeated measures using ecological momentary assessments
      (EMA). We review previous applications of EMA in research and clinical settings
      and the analytical tools that are useful for EMA research. We exemplify the
      analyses of EMA data with cases on physical activity data and affect and discuss
      the future challenges in the field.

PMID- 30105086
TI  - Bullet retrieval from the right hepatic vein using a controlled endovascular and
      transhepatic approach.
AB  - Venous bullet embolism is a rare complication of trauma. We describe a patient
      who sustained a gunshot wound. Computed tomography revealed antegrade
      embolization of the bullet to the right hepatic vein (RHV). The risk of not
      retrieving the bullet embolus and subsequent embolization to the pulmonary
      circulation includes pulmonary artery thrombosis, bleeding, or abscess formation.
      The bullet was retrieved through right internal jugular vein access; assisted by
      percutaneous transhepatic repositioning and endovascular balloon-immobilization
      of the bullet. The balloon served to "isolate" the bullet within the RHV to avoid
      the risk of endovascular migration to the pulmonary circulation. Transhepatic
      access allowed repositioning of the bullet within the RHV leading to successful
      snare retrieval. This technique demonstrates advantages of percutaneous and
      endovascular accesses, that repositioned and immobilized the bullet in the RHV to
      accomplish controlled endovascular retrieval.

PMID- 30105087
TI  - Karyotype characteristics and chromosomal polymorphism of Chironomus "annularius"
      sensu Strenzke (1959) (Diptera, Chironomidae) from the Caucasus region.
AB  - The study presents data on the karyotype characteristics and features of
      chromosomal polymorphism of Chironomus "annularius" sensu Strenzke (1959)
      (Diptera, Chironomidae) from three populations of the Caucasus region (South and
      Central Caucasus, and Eastern Ciscaucasia). We found 17 banding sequences in the
      Caucasian populations. We observed inversion polymorphism in almost all
      chromosome arms except for arm G. The genetic distances between all the studied
      populations of Ch. "annularius" were calculated using Nei criteria (1972). In
      spite of relative geographic proximity, the genetic distances between populations
      of the Caucasus are quite large, and they do not form a single cluster of
      Caucasian populations. The population of the South Caucasus goes to the European
      cluster, the population of the Central Caucasus goes to the Asian cluster and the
      population of Eastern Ciscaucasia does not belong to any of the outlined
      clusters. Principal component analysis (PCA) shows a similar picture. Two of the
      Caucasian populations do not follow Hardy-Weinberg expectation, there being a
      marked deficiency of heterozygotes in arms A, B and C, arguably, due to negative
      selection of heterozygotes or founder effect. All the obtained data are
      indicative of the complex genetic structure of Caucasian populations of Ch.
      "annularius" and total complexity microevolution processes occurring in the
      Caucasus region.

PMID- 30105088
TI  - Karyotypic variation in the long-whiskered catfish Pimelodusblochii Valenciennes,
      1840 (Siluriformes, Pimelodidae) from the lower Tapajos, Amazonas and Trombetas
      Rivers.
AB  - The genus Pimelodus LaCepede, 1803 comprises 35 formally recognized species
      distributed along the major neotropical river basins. Despite conservatism in
      diploid number with 2n=56, an intense variation of chromosomal morphology
      (karyotypic formula) has been documented in Pimelodus species. In the present
      study, we analyzed karyotypes of 20 specimens, identified as Pimelodusblochii
      Valenciennes, 1840 and collected from the lower courses of the Tapajos, Amazonas
      and Trombetas Rivers. The karyotypes were characterized by Giemsa conventional
      staining, C-banding, silver staining (Ag-NOR) and fluorescent in situ
      hybridization (FISH) with 5S and 18S rDNA probes. The karyotypes showed 2n=56
      chromosomes in fish from the Tapajos River. In contrast, fish from the Amazonas
      and Trombetas Rivers had 2n=58. The nucleolus organizing regions were labeled on
      the short arm of an acrocentric chromosome as demonstrated by silver staining and
      FISH. Signals for 18S and 5S rDNA were co-localized on one chromosome pair. Our
      results demonstrate karyotypic divergence between Tapajos and Amazonas-Trombetas
      populations of P.blochii, interpreted as supporting the existence of a species
      complex in this taxon.

PMID- 29568493
TI  - Validation of a yeast malate dehydrogenase 2 (Mdh2) antibody tested for use in
      western blots.
AB  - Malate dehydrogenases (Mdhs) reversibly convert malate to oxaloacetate and serve
      as important enzymes in several metabolic pathways. In the yeast Saccharomyces
      cerevisiae there are three Mdh isozymes, localized to different compartments in
      the cell. In order to identify specifically the Mdh2 isozyme, GenScript USA
      produced three different antibodies that we further tested by western blot. All
      three antibodies recognized the S. cerevisiae Mdh2 with different background and
      specificity properties. One of the antibodies had a relatively low background and
      high specificity and thus can be used for specific identification of Mdh2 in
      various experimental settings.

PMID- 30105089
TI  - Mechanical and Systems Biology of Cancer.
AB  - Mechanics and biochemical signaling are both often deregulated in cancer, leading
      toincreased cell invasiveness, proliferation, and survival. The dynamics and
      interactions of cytoskeletal components control basic mechanical properties, such
      as cell tension, stiffness, and engagement with the extracellular environment,
      which can lead to extracellular matrix remodeling. Intracellular mechanics can
      alter signaling and transcription factors, impacting cell decision making.
      Additionally, signaling from soluble and mechanical factors in the extracellular
      environment, such as substrate stiffness and ligand density, can modulate
      cytoskeletal dynamics. Computational models closely integrated with experimental
      support, incorporating cancer-specific parameters, can provide quantitative
      assessments and serve as predictive tools toward dissecting the feedback between
      signaling and mechanics and across multiple scales and domains in tumor
      progression.

PMID- 30105090
TI  - In Silico Prediction of Large-Scale Microbial Production Performance: Constraints
      for Getting Proper Data-Driven Models.
AB  - Industrial bioreactors range from 10.000 to 700.000 L and characteristically show
      different zones of substrate availabilities, dissolved gas concentrations and pH
      values reflecting physical, technical and economic constraints of scale-up.
      Microbial producers are fluctuating inside the bioreactors thereby experiencing
      frequently changing micro-environmental conditions. The external stimuli induce
      responses on microbial metabolism and on transcriptional regulation programs.
      Both may deteriorate the expected microbial production performance in large scale
      compared to expectations deduced from ideal, well-mixed lab-scale conditions.
      Accordingly, predictive tools are needed to quantify large-scale impacts
      considering bioreactor heterogeneities. The review shows that the time is right
      to combine simulations of microbial kinetics with calculations of large-scale
      environmental conditions to predict the bioreactor performance. Accordingly,
      basic experimental procedures and computational tools are presented to derive
      proper microbial models and hydrodynamic conditions, and to link both for
      bioreactor modeling. Particular emphasis is laid on the identification of gene
      regulatory networks as the implementation of such models will surely gain
      momentum in future studies.

PMID- 30105092
TI  - The mitochondrial genomes of the mesozoans Intoshia linei, Dicyema sp. and
      Dicyema japonicum.
AB  - The Dicyemida and Orthonectida are two groups of tiny, simple, vermiform
      parasites that have historically been united in a group named the Mesozoa. Both
      Dicyemida and Orthonectida have just two cell layers and appear to lack any
      defined tissues. They were initially thought to be evolutionary intermediates
      between protozoans and metazoans but more recent analyses indicate that they are
      protostomian metazoans that have undergone secondary simplification from a
      complex ancestor. Here we describe the first almost complete mitochondrial genome
      sequence from an orthonectid, Intoshia linei, and describe nine and eight
      mitochondrial protein-coding genes from Dicyema sp. and Dicyema japonicum,
      respectively. The 14,247 base pair long I. linei sequence has typical metazoan
      gene content, but is exceptionally AT-rich, and has a unique gene order. The data
      we have analysed from the Dicyemida provide very limited support for the
      suggestion that dicyemid mitochondrial genes are found on discrete mini-circles,
      as opposed to the large circular mitochondrial genomes that are typical of the
      Metazoa. The cox1 gene from dicyemid species has a series of conserved, in-frame
      deletions that is unique to this lineage. Using cox1 genes from across the genus
      Dicyema, we report the first internal phylogeny of this group.

PMID- 30105093
TI  - Prevalence, incidence and predictors of volunteer community health worker
      attrition in Kwale County, Kenya.
AB  - Introduction: In underserved populations, the contribution of community health
      workers (CHWs) is vital to the healthcare systems. Attrition of these workers
      causes critical breakdowns in the delivery of essential services to these
      populations. Literature on reasons for attrition is limited, although some have
      been identified in studies on sustainability of CHW programmes. These factors
      are, however, likely to be influenced by context. We measured CHW attrition and
      its predictors in a rural area in Kenya. Methods: We conducted a nested case
      control study and focus group discussions among CHWs involved in a maternal and
      child health project. A training register of 1005 CHWs was used to sample and
      follow CHWs for attrition. Incidence of CHW attrition was calculated using a
      Poisson model. Separately, we used logistic regression to determine predictors of
      CHW attrition. Results: Of the 1005 CHWs, 498 (49.6%) had left the project by the
      time of the study. The incidence of attrition was 46.8/1000 person-years (95% CI
      38.7 to 56.5). In the case-control study, lack of interest in peer organisation
      membership (OR 5.3; 95% CI 1.3 to 20.6) was associated with attrition. Absence of
      refresher training (OR 4.0; 95% CI 2.2 to 7.1) and receiving no feedback from
      supervisors (OR 2.0; 95% CI 1.0 to 3.9) were also associated with attrition.
      Discordance in expectations and perceived heavy workload were also identified as
      key reasons for attrition in the qualitative study. Conclusion: This study
      estimates high prevalence and incidence of CHW attrition in Kwale County, Kenya.
      Ongoing training, feedback and peer support are also important in enhancing
      retention of CHWs. Additionally, expectations regarding the roles and benefits of
      involvement in CHW work should be communicated clearly, and workload should be
      kept reasonable or negotiated with the CHWs.

PMID- 30105095
TI  - Sex and gender reporting in global health: new editorial policies.

PMID- 30105094
TI  - Lifetime prevalence, correlates and health consequences of gender-based violence
      victimisation and perpetration among men and women in Somalia.
AB  - Background: Humanitarian emergencies increase the risk of gender-based violence
      (GBV). We estimated the prevalence of GBV victimisation and perpetration among
      women and men in urban settings across Somalia, which has faced decades of war
      and natural disasters that have resulted in massive population displacements.
      Methods: A population-based survey was conducted in 14 urban areas across Somalia
      between December 2014 and November 2015. Results: A total of 2376 women and 2257
      men participated in the survey. One in five men (22.2%, 95% CI 20.5 to 23.9) and
      one in seven (15.5%; 95% CI 14.1 to 17.0) women reported physical or sexual
      violence victimisation during childhood. Among women, 35.6% (95% CI 33.4 to 37.9)
      reported adult lifetime experiences of physical or sexual intimate partner
      violence (IPV) and 16.5% (95% CI 15.1 to 18.1) reported adult lifetime experience
      of physical or sexual non-partner violence (NPV). Almost one-third of men (31.2%;
      95% CI 29.4 to 33.1) reported victimisation as an adult, the majority of which
      was physical violence. Twenty-two per cent (21.7%; 95% CI 19.5 to 24.1) of men
      reported lifetime sexual or physical IPV perpetration and 8.1% (95% CI 7.1 to
      9.3) reported lifetime sexual or physical NPV perpetration. Minority clan
      membership, displacement, exposure to parental violence and violence during
      childhood were common correlates of IPV and NPV victimisation and perpetration
      among women and men. Victimisation and perpetration were also strongly associated
      with recent depression and experiences of miscarriage or stillbirth. Conclusion:
      GBV is prevalent and spans all regions of Somalia. Programmes that support
      nurturing environments for children and provide health and psychosocial support
      for women and men are critical to prevent and respond to GBV.

PMID- 30105096
TI  - Prevalence and Outcome of Operative Vaginal Delivery among Mothers Who Gave Birth
      at Jimma University Medical Center, Southwest Ethiopia.
AB  - Background: Operative vaginal deliveries (OVD) are vaginal deliveries
      accomplished with the use of a vacuum device or forceps. If it is technically
      feasible and can be safely accomplished, termination of second stage labor by
      operative vaginal delivery is indicated in any condition threatening the mother
      or fetus that is likely to be relieved by delivery. Hence, the objective of this
      study is to assess the prevalence, common indication, outcome, and associated
      factors of operative vaginal delivery among mothers who gave birth in Jimma
      University Medical Center (JUMC). Method: A facility-based cross-sectional study
      design was used in maternity ward on 242 mothers who gave birth by operative
      vaginal delivery from December 01, 2016, to May 30, 2017. The clinical data were
      collected using a check list, recordings of intrapartum fetal and maternal state,
      and immediate fetomaternal outcomes. The study participants were recruited using
      consecutive sampling method. Sociodemographics and related data were collected at
      exit using structured interviewer administered questionnaire which was developed
      by reviewing different literature and the remaining information abstracted from
      patient charts. Data were entered to Epidata 3.1 and exported to SPSS version 21
      for analysis. Bivariate analysis was done to identify candidate variables using
      p<0.25. Multivariable logistic regression was used to control the effect of
      confounding variables and to identify factors affecting the fetomaternal outcome.
      Statistical significance was declared at P<0.05 using adjusted OR with 95% CI.
      Result: Out of the 2348 pregnant mothers who gave birth in the labor ward of JUMC
      during the 6 months of the study period, 242 (10.3%) were by operative vaginal
      delivery (OVD). The commonest indication for operative vaginal delivery is found
      to be nonreassuring fetal heart rate pattern, 136 (56.2%). Out of all neonates
      delivered by operative vaginal delivery 210 (86.8%) had favorable outcome. Of all
      mothers who gave birth by operative vaginal delivery 232 (95.9%) had favorable
      outcome. Type of instrument used for operative vaginal delivery (AOR=0.228,
      95%CI: 0.078, 0.671) and presence of grade two (AOR=0.163, 95%CI: 0.031, 0.858)
      and grade three (AOR=0.088,95%CI: 0.024,0.327) meconium stained amniotic fluid
      are factors affecting neonatal outcome while neonatal birth weight (AOR=0.007,
      95%CI: 0.000, 0.151) is factor affecting maternal outcome of operative vaginal
      delivery. Conclusion: Prevalence of operative vaginal delivery is found to be
      10.3% with the commonest indication of nonreassuring fetal heart rate pattern.
      Nearly all of mothers and neonates had favorable outcome. Type of instrument
      applied for operative vaginal delivery is the strongest predictor of neonatal
      outcome while neonatal birth weight is the only predictor of maternal outcome
      identified in this study.

PMID- 30105097
TI  - Appropriateness of Pharmacologic Prophylaxis against Deep Vein Thrombosis in
      Medical Wards of an Ethiopian Referral Hospital.
AB  - Background: Most of hospitalized patents are at risk of developing deep vein
      thrombosis (DVT). The use of pharmacological prophylaxis significantly reduces
      the incidence of thromboembolic events in high risk patients. The aim of this
      study was to assess appropriateness of DVT prophylaxis in hospitalized medical
      patients in an Ethiopian referral hospital. Methods: Cross-sectional study design
      was employed. Patients with a diagnosis of DVT, taking anticoagulant therapy, and
      those who refused to participate were excluded from the study. Two hundred and
      six patients were included in the study using simple random sampling method.
      Modified Padua Risk Assessment Model was used to determine the risk of
      thromboembolism. SPSS (version 21) was used for analysis. Result: The total risk
      score for the study subjects ranged from 0 to 11 with a mean score of 3.41 +/-
      2.55. Nearly half (47.6%) of study participants had high risk to develop
      thromboembolism. Thrombocytopenia (platelets < 50 billion/L) or coagulopathy,
      active hemorrhage, and end stage liver disease (INR > 1.5) were the frequently
      observed absolute contraindications that potentially prevent patients from
      receiving thromboprophylaxis. Thromboprophylaxis use in nearly one-third (31.6%)
      of patients admitted in the medical ward of UoGRH was irrational. Patients who
      had high risk for thromboembolism are more likely to be inappropriately managed
      for their risk of thromboembolism and patients with thrombocytopenia or
      coagulopathy were more likely to be managed appropriately. Conclusion: There is
      underutilization of pharmacologic thromboprophylaxis in medical ward patients.
      Physicians working there should be aware of risk factors for DVT and indications
      for pharmacologic thromboprophylaxis and should adhere to guideline
      recommendations.

PMID- 30105098
TI  - Payment Reforms for Prehospital Care Services in a Middle Income Country:
      Assessing Implementation and Patient Outcomes Using a Mixed-Methods Approach.
AB  - Introduction: Financing health systems constitutes a key element of well
      functioning healthcare system. Prior to 2015, two new financial arrangements
      (direct-pay and E-claim systems) were introduced on a voluntary basis which aimed
      to pool more financial resources and improve cash flow of prehospital care
      systems. The aims of this study were to (1) assess the effects of direct-pay
      system in terms of (a) timeliness of reimbursement to EMS agencies, (b) changes
      in clinical care processes, and (c) the outcomes of patient care as compared to
      previous system; (2) identify the reasons for or against EMS agencies to
      participate in direct-pay system mechanisms; (3) identify the emerging issues
      with potential to significantly further the advancement of EMS systems. Using a
      mixed-methods approach, retrospective datasets of 3,769,399 individual records of
      call responses from 2015 to 2017 were analyzed which compared EMS units with the
      direct-pay system against those without in terms of time flow of claim data and
      patient outcomes. For qualitative data, in-depth interviews were conducted.
      Results: EMS units participating in both systems had the highest percentages of
      financial claim being made in time as compared to those not participating in any
      (p=0.012). However, there were not any practically meaningful differences between
      EMS units participating and not participating in either of the payment systems in
      terms of patient care such as appropriateness of response time, airway
      management, and outcome of treatment. Analysis of data from focus-group and
      individual interviews ended up with a causal loop diagram demonstrating potential
      explanatory mechanisms for those findings. Conclusion: It is evident that
      progress has been made in terms of mobilising more financial inputs and improving
      financial information flow. However, there is no evidence of any changes in
      patient outcomes and quality of care. Furthermore, whether the progress is
      meaningful in filling the gaps of financial demands of the prehospital care
      systems is still questionable. Room for future improvement of prehospital care
      systems was discussed with implications for other countries.

PMID- 30105099
TI  - The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on
      Nonfasting Remnant Cholesterol in a Real World Population.
AB  - Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have
      demonstrated significant effects on low-density lipoprotein (LDL) cholesterol and
      nonhigh density lipoprotein (HDL) cholesterol. To date, there have been limited
      reports on the effect of PCSK9 inhibitors on remnant cholesterol. Objectives:
      Assess the effect of PCSK9 inhibitors on nonfasting remnant cholesterol in a real
      world population. Identify whether pretreatment triglyceride levels are
      associated with PCSK9 inhibition success as indicated by changes in remnant
      cholesterol levels. Methods: Patients in our adult lipid clinic (n = 109)
      receiving PCSK9 inhibition for atherosclerotic cardiovascular disease or familial
      hypercholesterolemia who had available pre- and post-PCSK9 inhibition standard
      nonfasting lipid data were, retrospectively, selected for data analysis. Remnant
      cholesterol was the difference between non-HDL and LDL cholesterol. LDL
      cholesterol was measured directly and calculated from Friedewald and
      Martin/Hopkins methods. Data were analyzed using repeated measures ANOVA and
      multivariable linear regression for differential effects on remnant and LDL
      cholesterol based upon pretreatment nonfasting triglyceride levels. Results:
      Remnant cholesterol as well as total, LDL, non-HDL cholesterol, and triglycerides
      decreased significantly (P<0.001) after PCSK9 inhibition. Patients with higher
      pretreatment triglyceride levels showed greater decrease in remnant cholesterol
      after PCSK9 inhibition (P<0.001) than those with lower pretreatment
      triglycerides. Conclusions: In patients receiving PCSK9 inhibitors, remnant
      cholesterol as determined from nonfasting blood was reduced in proportion to
      pretreatment triglycerides.

PMID- 30105100
TI  - Ropivacaine Plasma Concentrations after 192-Hour High Dose Epidural Ropivacaine
      Infusion in a Pediatric Patient without Side Effects.
AB  - This case report discusses continuous epidural administration of ropivacaine 0.56
      mg kg-1 h -1 for 8 days in a 7-year-old trauma patient to prevent pain, after
      performing a lower right and upper left leg guillotine amputation. Venous
      sampling after 8 days revealed bound and unbound ropivacaine concentrations of
      1.1 mg/l and 0.06 mg/l in plasma, respectively. Arterial sampling for bound and
      unbound ropivacaine was 1.2 mg/l and 0.05 mg/l in plasma, respectively. In this
      case report, long-term high dose epidural infiltration of ropivacaine did not
      result in severe side effects or complications. Further studies are needed to
      explore safety of these concentrations in larger populations of children.

PMID- 30105101
TI  - Fulminant Cerebral Fat Embolism: Case Description and Review of the Literature.
AB  - The release of fat and bone marrow fragments is a common occurrence following
      traumatic and nontraumatic events. In most cases, they go symptomless or cause
      only minor disturbances, but occasionally they can determine a multiorgan
      dysfunction whose severity ranges from mild to fatal. The authors describe the
      case of a patient who became deeply comatose and ultimately died after a traffic
      accident in which he suffered the exposed right femoral and tibial fracture in
      the absence of other injuries. He underwent the external fixation of the
      fractured bones 2 hours after the admission under general anesthesia. Three hours
      later, he failed to awake at the suspension of the anesthetic agents and became
      anisocoric; a CT scan demonstrated a diffuse cerebral edema with the herniation
      of the cerebellar tonsils; these abnormalities were unresponsive to the treatment
      and the brain death was one day later. The causes, the mechanisms, the symptoms,
      the prevention, and the treatment of the syndrome are reviewed and discussed.

PMID- 30105102
TI  - Prurigo Pigmentosa: A Clinicopathological Report of Three Middle Eastern
      Patients.
AB  - Prurigo pigmentosa is a unique cutaneous inflammatory disorder characterized by a
      sudden onset of pruritic and erythematous macules, urticarial papules, and
      plaques that may coalesce to form a reticulated pattern. Lesions typically heal
      within weeks leaving a reticulated and mottled postinflammatory
      hyperpigmentation. The majority of reported cases originate from Japan with much
      fewer cases described worldwide without predominant ethnicity. The
      histopathological features of prurigo pigmentosa can be nonspecific; however,
      distinct features exist for each stage of the disease. The aetiology of prurigo
      pigmentosa is not fully understood. However, ketoacidosis has been implicated in
      the pathogenesis and indeed prurigo pigmentosa has been associated with
      ketoacidotic states such as diabetes mellitus, fasting, dieting, and anorexia
      nervosa. In this report, we present 3 Jordanian patients with prurigo pigmentosa
      and describe their clinicopathological features. One patient developed prurigo
      pigmentosa while fasting during the month of Ramadan and another was undertaking
      a strict diet. No associations were identified in the third patient. In view of
      the largely nonspecific clinical and histological features, a high index of
      suspicion is required as many cases of prurigo pigmentosa are probably
      undiagnosed.

PMID- 30105103
TI  - Femoral Embolization after Cardiac Gunshot.
AB  - Bullet embolism is an uncommon complication from heart gunshot injuries because
      most of the patients die immediately after trauma. The low frequency of this
      complication combined with the possible absence of symptoms makes the condition a
      challenge for the surgeon, delaying diagnostics and leading to severe
      complications or death. In this case, a small calibre bullet entered the left
      ventricle and then impacted the femoris artery.

PMID- 30105104
TI  - Ectopic Papillary Thyroid Cancer with Distant Metastasis.
AB  - Ectopic thyroid tissue is a rare clinical entity wherein malignant lesions may
      arise, the most common one being papillary carcinoma. We present a case of a 68
      year-old female who presented with a growing mass in the right clavicle. An MR of
      the shoulder showed a soft tissue mass arising from the anterior margin of the
      right distal clavicle. A fine needle aspiration of the mass showed papillary
      thyroid carcinoma. PET/CT confirmed the clavicular and mediastinal mass. Excision
      of the clavicular mass and total thyroidectomy with modified right neck
      dissection were performed. Pathology revealed no evidence of malignancy in the
      thyroid; lymph nodes were positive for metastatic thyroid carcinoma. Postsurgery
      CT showed the superior mediastinal mass with surrounding adenopathy; radioiodine
      (RAI) treatment with dose of 142.1 mCi [5257.7 MBq] was recommended. Posttherapy
      whole-body scan (WBS) showed RAI avid tissue in the neck and superior
      mediastinum. Follow-up chest CT revealed pulmonary nodules that increased in
      number and size; a second RAI therapeutic dose was given. The posttherapy RAI WBS
      was negative. Repeat PET/CT showed multiple hypermetabolic lesions in the
      mediastinum, neck, lymph nodes, pulmonary nodes, and right shoulder. The FDG avid
      lesions with no RAI uptake suggested tumor dedifferentiation.

PMID- 30105105
TI  - Bilateral Pheochromocytomas in a Patient with Y175C Von Hippel-Lindau Mutation.
AB  - Von Hippel-Lindau (VHL) disease, caused by germline mutations in the VHL gene, is
      characterized by metachronously occurring tumors including pheochromocytoma,
      renal cell carcinoma (RCC), and hemangioblastoma. Although VHL disease leads to
      reduced life expectancy, its diagnosis is often missed and tumor screening
      guidelines are sparse. VHL protein acts as a tumor suppressor by targeting
      hypoxia-inducible factors (HIFs) for degradation through an oxygen-dependent
      mechanism. VHL mutants with more severely reduced HIF degrading function carry a
      high risk of RCC, while mutants with preserved HIF degrading capacity do not
      cause RCC but still lead to other tumors. VHL disease is classified into clinical
      types (1 and 2A-2C) based on this genotype-phenotype relationship. We report a
      case of bilateral pheochromocytomas and no other VHL-related tumors in a patient
      with Y175C VHL and show that this mutant preserves the ability to degrade HIF in
      normal oxygen conditions but, similar to the wild-type VHL protein, loses its
      ability to degrade HIF under hypoxic conditions. This study adds to the current
      understanding of the structure-function relationship of VHL mutations, which is
      important for risk stratification of future tumor development in the patients.

PMID- 30105106
TI  - Successful Management of Pheochromocytoma Detected in Pregnancy by Interval
      Adrenalectomy in a VHL Patient.
AB  - A 34-year-old mother with diabetes mellitus for 6 years presented in the late
      second trimester of her third pregnancy with new onset hypertension and
      characteristic hyperadrenergic spells. Clinical examination was unremarkable
      except a blood pressure of 170/110 mmhg. She had an elevated 24 hour urinary
      normetanephrine level with ultrasonic evidence of a hyperechoic hypervascular
      well-defined right supra renal mass of 6 x 5 cm in size which was very suggestive
      of a pheochromocytoma. Her management decisions were made by a multidisciplinary
      team which decided to deliver the baby by lower segment cesarean section (LSCS)
      as the pregnancy was advanced and to proceed with interval adrenalectomy after
      contrast enhanced computer tomography (CECT) of the abdomen with adrenal
      protocol. As a result a healthy baby was delivered by an uncomplicated elective
      LSCS at 36 weeks of POA. CECT abdomen with adrenal protocol confirmed a right
      sided pheochromocytoma without any evidence of metastasis. Uncomplicated
      laparoscopic right adrenalectomy led to a clinical and biochemical recovery of
      the patient while histology confirmed the pheochromocytoma without any evidence
      of invasion. Subsequent follow up revealed cerebellar hemangioblastomas and
      retinal angioma in the right eye which led to a clinical diagnosis of Von Hippel
      Lindau disease (VHL). Even though clinical criteria for Von Hippel Lindau disease
      were fulfilled, her VHL genetic test was negative. At present she and her family
      are under surveillance of the endocrine team.

PMID- 30105107
TI  - Thyroseq V3 Molecular Profiling for Tailoring the Surgical Management of Hurthle
      Cell Neoplasms.
AB  - Hurthle cell predominant thyroid nodules often confound the diagnostic utility of
      fine needle aspiration biopsy (FNAB) with cytology often interpreted as a Hurthle
      cell lesion with an indeterminate risk of malignancy, Bethesda category (BC) III
      or IV. Molecular diagnostics for Hurthle cell predominant nodules has also been
      disappointing in further defining the risk of malignancy. We present a case of a
      slowly enlarging nodule within a goiter initially reported as benign on FNAB, BC
      II but on subsequent FNAB suspicious for a Hurthle cell neoplasm, BC IV. The
      patient had initially requested a diagnostic lobectomy for a definitive diagnosis
      despite a higher risk of malignancy based on the size of the nodule > 4 cm alone.
      To better tailor this patient's treatment plan, a newer expanded gene mutation
      panel, ThyroSeq(r) v3 that includes copy number alterations (CNAs) and was
      recently found to have greater positive predictive value (PPV) for identifying
      Hurthle cell carcinoma (HCC), was performed on the FNAB material. Molecular
      profiling with ThyroSeq(r) v3 was able to predict a greater risk of carcinoma,
      making a more convincing argument in favor of total thyroidectomy. Surgical
      pathology confirmed a Hurthle cell carcinoma with 5 foci of angioinvasion and
      foci of capsular invasion.

PMID- 30105108
TI  - Novel TRAPPC11 Mutations in a Chinese Pedigree of Limb Girdle Muscular Dystrophy.
AB  - Limb girdle muscular dystrophies (LGMDs) are a heterogeneous group of genetic
      myopathies leading primarily to proximal muscle weakness. It is caused by
      mutations at over 50 known genetic loci typically from mutations in genes
      encoding constituents of the sarcolemmal dystrophin complex or related functions.
      Herein we describe the case of two siblings with LGMD that were investigated
      using whole-exome sequencing followed by Sanger sequencing validation of a
      specific double-mutation in the TRAPPC11 gene. Further, from parental sequencing
      we determined the mode of transmission, a double heterozygous mutation at the
      maternal and paternal alleles. The two mutations detected have not been described
      in other patients.

PMID- 30105109
TI  - Diplopia: A Rare Manifestation of Neuroborreliosis.
AB  - Early disseminated Lyme disease typically presents with cardiac, rheumatologic,
      or neurologic symptoms. Though uncommon, Borrelia burgdorferi can invade the
      central nervous system and cause neuroborreliosis. In these patients, facial
      palsy, headache, and stiffness of the neck are the most common presenting
      symptoms. Our case describes a patient with oculomotor nerve palsy manifesting as
      double vision as the initial presentation of neuroborreliosis.

PMID- 30105110
TI  - Vaginal Angiomyofibroblastoma: A Case Report and Review of Diagnostic Imaging.
AB  - Background: Angiomyofibroblastoma (AMFB) is a benign mesenchymal tumor most
      commonly found in the female genital tract of premenopausal women. Although rare,
      AMFB is an important consideration in the differential diagnosis of vulvar and
      vaginal masses, as it must be distinguished from aggressive angiomyxoma (AA), a
      locally recurrent, invasive, and damaging tumor with similar clinical and
      pathologic findings. Case: We describe a patient with a 4 cm vaginal AMFB and the
      relevant preoperative radiographic imaging findings. Conclusion: Preoperative
      diagnosis of AMFB remains difficult. Common findings on magnetic resonance
      imaging and transvaginal sonography are described. We conclude that both
      transvaginal ultrasound and MRI are potentially useful imaging modalities in the
      preoperative assessment of vulvar and vaginal AMFB, with more data needed to
      determine superiority of one modality over the other.

PMID- 30105111
TI  - Undifferentiated Pleomorphic Sarcoma of Liver: Case Report and Review of the
      Literature.
AB  - Undifferentiated pleomorphic sarcoma (UPS), previously known as malignant fibrous
      histiocytoma (MFH), is rarely reported in the liver as a primary site. We report
      a case of a previously healthy 56-year-old male, who presented with abdominal
      pain and jaundice. The patient was originally diagnosed with cholecystitis,
      treated with cholecystectomy, which was complicated by abdominal abscess. One
      week following discharge, the patient was readmitted with fever, chills, and
      leukocytosis. Computed tomography (CT) guided liver biopsies demonstrated an
      epithelioid to spindle cell neoplasm with markedly atypical nuclei and prominent
      necrosis infiltrating between hepatocytes. Immunohistochemical studies were
      negative for epithelial, melanocytic, and hematolymphoid differentiation.
      Positron emission tomography (PET) was performed, which showed a single markedly
      hypermetabolic central hepatic mass (14 x 8.5 x 8.5 cm) with likely central
      necrosis, consistent with primary malignancy. The patient was treated with one
      cycle of chemotherapy (doxorubicin and ifosfamide), refusing additional cycle due
      to medication side effects. The patient subsequently succumbed to complications
      associated with the malignancy and died within 19 days of diagnosis.

PMID- 30105112
TI  - Laryngeal Inflammatory Pseudotumour Secondary to Mycobacterium kansasii.
AB  - Background: Inflammatory pseudotumours (IPT) are rare benign tumours
      characterised by spindle-shaped histiocyte proliferation often mimicking a soft
      tissue sarcoma. They can occur in different parts of the body and various
      aetiological factors have been proposed. To our knowledge this is the first case
      report of IPT of the larynx caused by mycobacterial disease. Case Report: We
      report a case of IPT of the larynx in an immunocompromised 81-year-old lady
      presenting with stridor and dysphagia with known disseminated Mycobacterium
      kansasii of the lungs. Conclusion: This case demonstrates both the clinical and
      histological difficulties in making the diagnosis of IPT. A high index of
      suspicion is needed, and the importance of a multidisciplinary approach in the
      work-up, diagnosis, and management is highlighted.

PMID- 30105113
TI  - Drug-Induced Liver Injury Associated with the Use of Everolimus in a Liver
      Transplant Patient.
AB  - Drug-induced liver injury (DILI) has not been previously reported as a
      complication of treatment with everolimus. A 56-year-old Caucasian male liver
      transplant recipient developed DILI after receiving everolimus. Elevations in
      transaminase levels occurred within a week of starting everolimus and an upward
      trend in the transaminase levels continued with supporting histopathologic
      changes confirmed by liver biopsy. Within one week of drug discontinuation, his
      liver enzymes normalized to baseline. This report includes a brief review of the
      pharmacokinetic properties of everolimus, a review of the relevant literature,
      and an analysis using the RUCAM and Naranjo algorithms.

PMID- 30105114
TI  - Rupture of a Calyceal Diverticulum Secondary to Ureteroscopy: A Rare
      Complication.
AB  - We present a case of a 45-year-old female who experienced rupture of a right
      calyceal diverticulum caused by ureteroscopy. Fifteen hours after the operation,
      she had severe right flank pain and a high fever (38.9 degrees C). Computed
      tomography revealed perinephric extravasation of urine and bleeding inside the
      diverticulum. We diagnosed rupture of a calyceal diverticulum; therefore, we
      continued antibiotic administration and pain relief medication. She became
      afebrile on postoperative day 4 and was discharged from the hospital on
      postoperative day 7. Owing to renal cortex thinning in the diverticula,
      ureteroscopy is associated with a risk of rupture of calyceal diverticula.

PMID- 30105115
TI  - In Vitro and In Vivo Quality Evaluation of Glibenclamide Tablets Marketed in
      Addis Ababa, Ethiopia.
AB  - Good quality drugs fulfilling the regulatory parameters and produced per the
      current good manufacturing (CGMP) standards are very critical for best
      therapeutic outcome in patient therapy. Hence, this study assesses quality as
      well as physicochemical bioequivalence of five brands of glibenclamide tablets
      marketed in Addis Ababa using in vitro and in vivo methods. Friability,
      disintegration, dissolution, and assay for the content of active ingredients were
      evaluated using the methods described in the British Pharmacopeia (2009) and
      United States Pharmacopeia (2007). All the brands of glibenclamide tablets
      complied with the official specification for hardness, friability,
      disintegration, and assay. Difference factor (f1) values were less than 15 and
      similarity factor (f2) values were greater than 50 for all products of
      glibenclamide. The hypoglycemic effect of different products of glibenclamide
      tablets was evaluated on normoglycemic mice. The in vivo studies indicated that
      there is no significant difference in percent reduction of blood glucose level
      between the brands of glibenclamide and the innovator product (p > 0.05). Hence,
      based on the in vivo results and in vitro dissolution studies, the brands might
      be substituted with the innovator product in clinical practice.

PMID- 30105116
TI  - Identification of Two Novel Mutations in Aminomethyltransferase Gene in Cases of
      Glycine Encephalopathy.
AB  - In this study, we report three cases of nonketotic hyperglycinemia (NKHG)
      diagnosed biochemically and molecularly. Clinical exome analysis in two families
      revealed two novel mutations in the aminomethyltransferase (AMT) gene, that is,
      c.14_15insT (p.Ser6LysfsTer22) and c.259-2A > T, both of them adversely affecting
      the protein. This is the first report of AMT gene mutations in NKHG from India.
      Prenatal diagnosis in the first family showed an unaffected fetus in the third
      pregnancy. The role of AMT protein is pivotal for the synthesis of 5,10-methylene
      tetrahydrofolate, the first metabolite in one-carbon metabolism that regulates
      DNA synthesis, repair, and methylation.

PMID- 30105117
TI  - Oxidative Stress and Polymorphism in MTHFR SNPs (677 and 1298) in Paternal Sperm
      DNA is Associated with an Increased Risk of Retinoblastoma in Their Children: A
      Case-Control Study.
AB  - Sperm DNA is considered as the most vulnerable to oxidative stress-induced damage
      that also impairs global sperm DNA methylation leading to sperm-associated
      pathologies. C677T and A1298C polymorphisms of the methylene tetrahydrofolate
      reductase (MTHFR) gene affect MTHFR enzyme activity. This study was planned as a
      case-control study to determine the MTHFR gene polymorphisms in the fathers of
      children affected with sporadic nonfamilial heritable retinoblastoma in an Indian
      population. MTHFR polymorphisms for single nucleotide polymorphisms 677 and 1298
      were also determined in sporadic nonfamilial heritable retinoblastoma patients to
      estimate the risk for retinoblastoma development and to evaluate the role of
      MTHFR in retinoblastoma pathogenesis.

PMID- 30105118
TI  - Paroxysmal Movement Disorder and Epilepsy Caused by a De Novo Truncating Mutation
      in KAT6A.
AB  - Mutations in KAT6A encoding a histone acetyltransferase involved in chromatin
      remodeling and in other genes involved in histone acetylation and/or
      deacetylation have been implicated in broad phenotypes of congenital and
      developmental abnormalities. However, limited genotype-phenotype correlations are
      available for some of the most rare or recently reported genetic disorders
      related to chromatin dysregulation. We hereby report a de novo truncating
      mutation in KAT6A (c.3338C > G; p.S1113X) in a young male patient with
      intellectual disability associated with impaired speech and autistic features,
      who also presented with infantile seizures and a complex movement disorder
      phenotype with paroxysmal episodes of abnormal startle responses.

PMID- 30105119
TI  - A Case of Shwachman-Diamond Syndrome who Presented with Hypotonia.
AB  - We present a patient with failure to thrive and severe hypotonia, who was
      initially suspected of having a neurometabolic disease but later diagnosed as
      Shwachman-Diamond syndrome (SDS), which was genetically confirmed. SDS is a
      multisystemic disease, which is characterized by exocrine pancreatic deficiency,
      bone marrow dysfunction with increased risk for malignant transformation, and
      skeletal abnormalities. It should be included in differential diagnosis of
      patients with failure to thrive and unexplained neurodevelopmental delay with
      neutropenia.

PMID- 30105120
TI  - Multiple Hereditary Exostoses: Report of an EXT2 Gene Mutation in a Colombian
      Family.
AB  - Multiple hereditary exostoses (MHE) is a rare disease with autosomal dominant
      inheritance, caused by heterozygous germline mutations in the EXT1 or EXT2 genes.
      This disorder is characterized by the growth of prominences surrounded by
      cartilage in the growth plates and the long bones. Here, we report a family
      affected by MHE. In this family, a pathogenic variant c.544C > T (p. Arg182Ter)
      was identified in the EXT2 gene. This variant has been previously described in
      the literature, and here we are reporting the relationship with clinical
      findings. MHE is suspected according to the clinical manifestations; molecular
      research should be performed to establish the most frequent mutations. A support,
      diagnosis, and follow-up group should be created, and genetic counseling should
      be available for patients and families.

PMID- 30105121
TI  - An Interesting and Unique Case of 8p23.3p23.1 Deletion and 8p23.1p11.1
      Interstitial Duplication Syndrome.
AB  - We report an interesting case of a male toddler with global developmental delay,
      dysmorphic facies, seizures, and acyanotic heart disease. Detailed evaluation
      revealed absent corpus callosum with large doubly committed ventricular septal
      defect (VSD) and 8p23.3p23.1 deletion and 8p23.1p11.1 interstitial duplication
      syndrome. In comparison to similar reports of 8p deletion and inverted
      duplication syndrome, the uniqueness of this report lies in the fact that the
      congenital heart defect occurred without the GATA4 gene involvement, and the
      nervous system involvement was more extensive.

PMID- 30105122
TI  - Report of the Third Family with Multiple Mitochondrial Dysfunctions Syndrome 5
      Caused by the Founder Variant p.(Glu87Lys) in ISCA1.
AB  - Iron-sulfur cluster assembly 1 (ISCA1) is one of the essential proteins operating
      in the mitochondrial iron-sulfur (Fe-S) cluster biogenesis pathway. We reported
      the variant c.259G > A [p.(Glu87Lys)] in homozygous state in exon 4 of the ISCA1
      gene as the likely cause of multiple mitochondrial dysfunction syndrome 5 in a
      previous publication. We now report the third patient with the same phenotype and
      variant, further supporting the possibility of a founder event. Our observation
      confirms the clinical presentation associated with a probable founder variant in
      this condition.

PMID- 30105123
TI  - Challenges in Diagnosing Rare Genetic Causes of Common In Utero Presentations:
      Report of Two Patients with Mucolipidosis Type II (I-Cell Disease).
AB  - Traditional approaches to prenatal genetic diagnosis for common presentations
      such as short femurs or intrauterine growth restriction are imperfect, and whole
      exome sequencing is an emerging option. Mucolipidosis type II (I-cell disease) is
      an ultra-rare autosomal recessive lysosomal storage disorder with the potential
      for prenatal-onset skeletal and placental manifestations. We describe the
      prenatal signs in two recent unrelated patients with confirmed diagnoses soon
      after birth. In both cases, parents were consanguineous but there was no known
      family history of mucolipidosis type II. False reassurance was provided after
      negative testing for another disease with overlapping prenatal manifestations
      already present in one of the families, emphasizing that offspring of
      consanguineous parents can be at risk for more than one recessive condition. Our
      experience illustrates the potential advantages in expanding prenatal
      applications of WES for the identification of rare single gene disorders in
      offspring of consanguineous unions.

PMID- 30105124
TI  - 22q11.2 Microduplication: An Enigmatic Genetic Disorder.
AB  - Microduplication of 22q11.2 involves having an extra copy at position q11.2 on
      chromosome 22. Very few cases have been reported but the real incidence may be
      higher as the absence of obvious clinical signs makes diagnosis difficult. In the
      cases that are diagnosed, the phenotype is extremely variable. We describe a case
      of severe micrognathia, cleft palate, and Pierre-Robin sequence. A prenatal
      ultrasound showed severe micrognathia and subsequent microarray done on
      amniocentesis revealed the microduplication of 22q11.2, which was confirmed
      postnatally. Although micrognathia has often been detected in this
      microduplication, the constellation of these findings has not been previously
      described.

PMID- 30105126
TI  - Tension pneumocephalus from skull base surgery: A case report and review of the
      literature.
AB  - Background: Tension pneumocephalus from skull base surgery is a rare occurrence
      that mandates urgent neurosurgical attention. Case Description: We describe a
      case of tension pneumocephalus secondary to an endoscopic endonasal resection of
      an adamantinomatous craniopharyngioma and how it was successfully managed at our
      institution. Conclusion: Our experience reflects that definitive treatment of
      tension pneumocephalus is required with multilayered dural repair, but
      temporising measures should be used immediately to prevent neurological
      deterioration prior to the definitive repair.

PMID- 30105125
TI  - Microvascular anastomosis under 3D exoscope or endoscope magnification: A proof
      of-concept study.
AB  - Background: Extracranial-intracranial bypass is a challenging procedure that
      requires special microsurgical skills and an operative microscope. The exoscope
      is a tool for neurosurgical visualization that provides view on a heads-up
      display similar to an endoscope, but positioned external to the operating field,
      like a microscope. The authors carried out a proof-of-concept study evaluating
      the feasibility and effectiveness of performing microvascular bypass using
      various new exoscopic tools. Methods: We evaluated microsurgical procedures using
      a three-dimensional (3D) endoscope, hands-free robotic automated positioning two
      dimensional (2D) exoscope, and an ocular-free 3D exoscope, including surgical
      gauze knot tying, surgical glove cutting, placental vessel anastomoses, and rat
      vessel anastomoses. Image quality, effectiveness, and feasibility of each
      technique were compared among different visualization tools and to a standard
      operative microscope. Results: 3D endoscopy produced relatively unsatisfactory
      resolution imaging. It was shown to be sufficient for knot tying and anastomosis
      of a placental artery, but was not suitable for anastomosis in rats. The 2D
      exoscope provided higher resolution imaging, but was not adequate for all
      maneuvers because of lack of depth perception. The 3D exoscope was shown to be
      functional to complete all maneuvers because of its depth perception and higher
      resolution. Conclusion: Depth perception and high resolution at highest
      magnification are required for microvascular bypass procedures. Execution of
      standard microanastomosis techniques was unsuccessful using 2D imaging modalities
      because of depth-perception-related constraints. Microvascular anastomosis is
      feasible under 3D exoscopic visualization; however, at highest magnification, the
      depth perception is inferior to that provided by a standard operative microscope,
      which impedes the procedure.

PMID- 30105127
TI  - Epidural venous plexus engorgement due to inferior vena cava thrombosis resulting
      in cauda equina syndrome: Case report and literature review.
AB  - Background: Epidural venous plexus congestion at L5-S1 due to inferior vena cava
      (IVC) thrombosis led to an acute cauda equina syndrome (CES). Laminectomy to rule
      out an epidural abscess, allowing for resection of the dilated veins, led to
      immediate symptom resolution. Case Description: A 47-year-old male presented with
      acute urinary retention and left greater than right lower extremity paresis of 2
      weeks duration. Magnetic resonance imaging (MRI) revealed a contrast-enhancing
      space-occupying anterior epidural L5-S1 level lesion resulting in cauda equina
      compression. As the patient was septic, he underwent an emergency laminectomy for
      a presumed epidural abscess. Intraoperative findings, however, documented a
      markedly dilated epidural venous plexus secondary to a newly diagnosed IVC
      thrombus. One day postoperatively, the patient was symptom-free and
      neurologically intact. Conclusions: Here we report a patient who uniquely
      presented with a CES characterized by acute paraparesis. This was attributed to a
      massively engorged anterior lumbar epidural venous plexus attributed to newly
      diagnosed IVC thrombus.

PMID- 30105129
TI  - Rapid malignant progression of an intraparenchymal choroid plexus papillomas.
AB  - Background: Choroid plexus tumors (CPTs) are rare neoplasms accounting for only
      0.3-0.6% of all brain tumors in adults and 2-5% in children. The World Health
      Organization (WHO) classification describes three histological grades: grade I is
      choroid plexus papilloma (CPP), grade II is atypical papilloma, and grade III is
      the malignant form of carcinoma. In adults, CPTs rarely have a supratentorial
      localization. Case Description: Here we report a very rare case of an
      intraparenchymal parietal CPP with a rapid histological transition from grade I
      to grade III WHO in a 67-year-old man, in <7 months. Conclusion: Because of the
      rarity of these oncotypes, descriptions of each new case are useful, mostly to
      consider this diagnostic entity in extraventricular brain tumors of adults,
      despite an unusual location.

PMID- 30105128
TI  - Pseudotumor cerebri comorbid with meningioma: A review and case series.
AB  - Background: Pseudotumor cerebri (PTC), which has a prevalence in the general
      population of 1 to 2 out of 100,000, presents with raised intracranial pressure
      (ICP) but generally lacks a space occupying lesion. Case Description: Patient 1
      is a 32-year-old woman with a history of multiple meningiomas. Upon presentation
      to our institution, her clinical exam was notable for a right sixth nerve palsy.
      An integrated diagnosis of PTC was made and shunting for the cerebrospinal fluid
      (CSF) diversion was recommended. Approximately 6 weeks after surgery, the patient
      exhibited complete symptom resolution and discontinued all medications. Patient 2
      is a 40-year-old woman with history of meningioma causing partial obstruction of
      the right transverse sigmoid sinus. She agreed to undergo surgery for the left
      ventriculoperitoneal (VP) shunt placement, for management of her PTC.
      Postoperatively, the patient reported that her vision significantly improved.
      Patient 3 is a 49-year-old woman with history of meningioma who presented with
      left visual field cut. A right frontal VP shunt was recommended for the treatment
      of PTC. Postoperatively, the patient reported significant symptom improvement and
      resolution of visual complaints. Conclusion: This case series demonstrates that
      it is important to keep PTC in the differential diagnosis even when mass lesions
      such as meningiomas are discovered. Although PTC, as the name indicates, is
      classically diagnosed in patients without intracranial tumors, it is critical
      that this not be used as an absolute exclusion criterion. Finally, this case
      series supports the hypothesis that venous obstruction can result in PTC.

PMID- 30105130
TI  - Management of patent foramen ovale in patients with cryptogenic stroke: Is device
      closure superior to medical treatment? A brief review.
AB  - Background: Recent randomized controlled trial (RCTs) comparing percutaneous
      closure with antithrombotic treatment in patients with patent foramen ovale (PFO)
      and cryptogenic stroke revealed inconsistent results. Indeed, there is still no
      consensus on the management of these patients, namely closure or medical therapy
      treatment. Methods: To take stock of the PFO management after cryptogenic stroke,
      we conducted a literature review that included 16 articles dealing with different
      therapeutic strategies and long-term outcomes of these results. Results: The
      reviewed studies showed great methodological diversity rendering an exhaustive
      and balanced comparison between studies difficult. Low recurrence rates under
      prevention regimens, crossovers, procedure- and device-related complications, as
      well as inappropriate patient selection might explain the inconsistency of
      trials. However, despite the methodological heterogeneity certain patterns could
      be detected. It appears that device closure as secondary prevention measure is an
      effective and safe procedure reducing the recurrence of neurological events in
      cryptogenic stroke patients <60 years with large PFOs. Standardization of
      procedures and larger trials are needed to arrive to definitive conclusions.
      Conclusion: In cryptogenic stroke patients <60 years with large PFOs, PFO closure
      seems to be safe and more effective compared to medical treatment alone. For all
      other patients group, for example, patients >60 years further trials are needed
      to clarify the role of PFO closure.

PMID- 30105132
TI  - Short review of randomized controlled trials (RCTs) for Surgical Neurology
      International: Two important RCT articles for 2018 - Part I.

PMID- 30105131
TI  - Bilateral stereotactic lesions and chronic stimulation of the anterior thalamic
      nuclei for treatment of pharmacoresistant epilepsy.
AB  - Background: The use of the anterior nucleus of thalamus (ANT) as a target for
      treatment of pharmacoresistant epilepsy is based on its crucial role in seizure
      propagation. We describe results of chronic bilateral ANT stimulation and
      bilateral ANT lesions in 31 patients with refractory epilepsy. Methods: ANT DBS
      was performed in 12 patients (group I) and bilateral stereotactic radiofrequency
      lesions of ANT were performed in 19 patients (group II). Targeting was based on
      stereotactic atlas information with correction of the final coordinates according
      to the location of anatomical landmarks and intraoperative microelectrode
      recording data. Results: Both groups were similar in age, gender, seizures
      frequency, and duration of disease. The median x, y, and z coordinates of ANT
      were found to be 2.9, 5, and 11 mm anterior, lateral, and superior to the mid
      commissural point, respectively. Mean seizures reduction reached 80.3% in group
      of patients with ANT DBS with two nonresponders and 91.2% in group of patients
      with lesions. Five patients from group I and three patients from group II became
      seizure-free. The morbidity rate was low in both groups. Conclusions:
      Stereotactic anterior thalamotomy and chronic ANT stimulation are both effective
      for seizure control in epilepsy originated from frontal and temporal lobes. ANT
      lesions and stimulation were more effective for secondary-generalized seizures
      compared to simple partial seizures.

PMID- 30105133
TI  - A giant partially thrombosed, partially filling, and partially calcified
      intracranial aneurysm.

PMID- 30105135
TI  - One burr-hole craniotomy: Anterior interhemispheric approach in Helsinki
      Neurosurgery.
AB  - Background: In this video-abstract, we present a one burr-hole craniotomy for the
      anterior interhemispheric approach developed in Helsinki Neurosurgery to access
      the medial surface of cerebral hemispheres, the falx cerebri, the distal segment
      of the anterior cerebral artery, the corpus callosum, the third ventricle, and
      the lateral ventricles. Therefore, preoperative imaging is essential to achieve
      an optimal operative corridor for safest and more effcient approach. Case
      Description: The patient with a no ruptured right pericallosal aneurysm is placed
      in semi-sitting position. A midline single-layer curved skin incision is made
      behind the hairline with more extension to the side of the planned bone flap.
      Strong retraction with hooks keeps a clean space for craniotomy. Hemostatic Raney
      clips are placed at the posterior border of the wound. A burr-hole is made over
      the superior sagittal sinus at the posterior border of the bone flap. The bone is
      detached from the dura anteriorly with blunt dissectors. Thus, we avoid harming
      the superior cerebral veins distributed at the posterior frontal area. After the
      detachment of the dura, a craniotomy around the superior sagittal sinus is
      performed to expose 2-3 cm of the dura lateral to the sagittal sinus. Moreover,
      the craniotomy extends slightly over the contralateral side to allow some
      retraction of the sagittal sinus. Two cuts, from both sites of the burr-hole, are
      joined along the anterior midline by thinning the bone with craniotome blade
      without the footplate. A few drill holes are made for tack-up sutures. The bone
      is cracked along the thinned midline. Finally, a hemostatic agent covers the
      sagittal sinus and a sinus-based dura opening is performed under the microscope.
      Conclusion: The described one burr-hole craniotomy may represent a more efficient
      manner for performing an anterior interhemispheric approach. Videolink:
      http://surgicalneurologyint.com/videogallery/anterior-interhemispheric-approach/.

PMID- 30105134
TI  - Transzygomatic approach plus mini-peeling of middle fossa for devascularization
      of sphenoid wing meningiomas. Technical note.
AB  - Background: Sphenoid wing meningiomas account for 20% of supratentorial
      meningiomas. The main supply of these tumors is provided by branches of the
      middle and accessory meningeal arteries. Surgical resection of meningiomas
      requires early tumor devascularization. Our objective is to present the role of
      transzygomatic approach plus mini-peeling of the anterior third of the middle
      fossa in the extradural identification and coagulation of branches of middle and
      accessory meningeal arteries involved in tumor supply. Methods: Ten formalin
      fixed, silicone-injected cadaveric heads were used. On each side a transzygomatic
      approach plus mini-peeling of the anterior third of the middle fossa was
      performed. Between 2005 and 2017, the authors applied this technique for the
      resection of sphenoid wing meningiomas in 28 patients. Results: The mean age of
      patients was 54 years. Thirteen tumors could be classified as medial-third type,
      6 as middle-third type, and 4 tumors were lateral-third type. Five tumors
      represented combined types. Of these, 3 tumors involved the medial and middle
      third of the sphenoid wing and 2 involved the entire wing. Surgical resection was
      classified as Simpson I/II in 24 patients (86%). There were no permanent deficits
      or postoperative mortality. Conclusions: The transzygomatic approach combined
      with mini-peeling of the anterior third of the middle fossa is effective in
      allowing early devascularization of sphenoid wing meningiomas. These maneuvers
      are particularly important during resection of large tumors.

PMID- 30105137
TI  - Dorsal accessory ectopic breast with polythelia - A marker of occult spinal
      dysraphism.
AB  - Background: Accessory breast, also known as supernumerary breasts, polymastia, or
      mammae erraticae, is a clinical condition of having an additional breast.
      Accessory breasts are usually seen along the embryonic milk line, with the
      majority located in the axilla. Polythelia is the presence of an additional
      nipple. We report a rare case of dorsal accessory ectopic breast with three
      nipples (two well formed and one rudimentary) occurring along with
      lipomeningomyelocele and diastematomyelia. Case Description: We report the case
      of an 18-year-old female who presented with chief complaints of swelling over the
      upper back since birth and spastic weakness of bilateral lower limbs with
      inability to walk since 2 years. Three-dimensional computed tomography scan of
      the dorsal spine was suggestive of a wide bony defect in the posterior spinal
      elements from D3 to D9 vertebrae. Diastematomyelia was also seen. Magnetic
      resonance imaging of the dorsal spine was suggestive of a complex spinal
      dysraphism with lipomeningomyelocele and diastematomyelia. During surgery, the
      patient's accessory breast was removed, lipomatous tissue and bony septum were
      excised, and dural repair was done. Histopathological examination was consistent
      with accessory ectopic breast with lipomeningomyelocele. Conclusion: Dorsal
      accessory breast, although a rare entity, whenever present should alert the
      clinician regarding the possibility of an underlying occult spinal dysraphism
      (OSD). Therefore, dorsal accessory breast can also be considered as a marker of
      OSD.

PMID- 30105136
TI  - Cervical C2 to C4 schwannoma with intratumoral hemorrhage presenting as acute
      spastic quadriparesis: A rare case report.
AB  - Background: Spinal schwannomas are slow growing, benign nerve sheath tumors.
      These may be asymptomatic or may present as backache with radicular pain, slowly
      progressive neurological deficits, but rarely with acute spastic quadriparesis
      attributed to intratumoral hemorrhage. Case Description: A 38-year-old male
      presented with the chief complaint of neck pain radiating to the left upper
      extremity for the last 8 months. On admission, he exhibited diffuse hyper
      reflexia but had no motor or sensory deficit. Magnetic resonance imaging showed a
      solid-cystic intradural extramedullary (IDEM) C2 to C4 mass severely compressing
      the spinal cord. The same day the patient acutely developed a spastic
      quadriparesis. Immediately, a partial C2, C3, and C4 laminectomy was performed
      for tumor excision; within 5 postoperative days, he fully regained neurological
      function. The final histopathology was consistent with a "schwannoma showing
      areas of congestion and hemorrhage." Conclusion: Spinal schwannomas rarely
      present with intratumoral hemorrhage and acute spastic quadriparesis. Immediate
      operative decompression may lead to excellent postoperative neurological
      recovery.

PMID- 30105139
TI  - Epithelioid pituicytoma: An unusual case report.
AB  - Background: Pituicytomas are considered World Health Organization Grade I
      malignancies. Until September 2017, a total of 81 cases of pituicytomas were
      diagnosed and described in literature. We present such a case in which
      histopathology shows an epithelioid pattern, a rare variant of pituicytoma. As
      far as we know, this is only the second such case described in the literature.
      Case Description: A 61-year-old male patient presented with complaints of
      progressive decrease in visual acuity for about 7 months, worse on the left side.
      Laboratory and endocrinological investigation returned normal values. Magnetic
      resonance imaging revealed a mixed solid-cystic lesion, measuring about 3.1 * 2.2
      * 2.9 cm. The lesion presented with intermediate signal intensity in T1 and T2
      sequences and showed avid postcontrast enhancement. The patient underwent
      resection through a left pterional approach. Pathology revealed a glial neoplasm
      with an epithelioid pattern and moderate cellularity with rounded-elongated cell
      nuclei and with a broad eosinophilic cytoplasm. Absence of cellular pleomorphism,
      any mitotic figures, or areas of necrosis was noted. Conclusion: The epithelioid
      variant of pituicytomas differs from the commonly encountered forms of this tumor
      which typically present in a fascicular pattern. Microsurgical resection is the
      treatment of choice. However, in many cases, subtotal resection was performed
      because of a considerable risk for neurovascular injuries.

PMID- 30105138
TI  - Preoperative and intraoperative perfusion magnetic resonance imaging in a RELA
      fusion-positive anaplastic ependymoma: A case report.
AB  - Background: Ependymomas are rare neuroepithelial tumors thought to arise from
      radial glial precursor cells lining the walls of the ventricles and central canal
      of the brain and spinal cord, respectively. Histopathological classification,
      according to World Health Organization criteria, has only recently defined the
      RELA-fusion positive ependymoma. These tumors may account for 70% of
      supratentorial ependymomas in children and represent an aggressive entity
      distinct from other ependymomas. Case Description: Here we present the case of a
      patient with RELA-fusion positive ependymoma of the frontal lobe in whom we used
      preoperative and intraoperative magnetic resonance (MR) perfusion imaging. In
      this first demonstrated intraoperative evaluation of MR perfusion in ependymoma,
      increased peripheral perfusion of the lesion in a ring-like manner with a
      discrete cutoff around the surgical margin correlated with intraoperative
      findings of a clear border between the tumor and brain, as well as pathological
      findings of increased MIB index and hypercellularity-specifically within solid
      tumor components. An abnormal perfusion pattern also suggested an aggressive
      lesion, which was later confirmed on pathological analysis. In addition,
      intraoperative MR perfusion improved detection of tumor tissue in combination
      with traditional T1-weighted contrast-enhanced methods, which increased extent of
      resection. Conclusions: MR perfusion imaging may be a useful method for
      delineating tumor aggressiveness and borders, which can be prognostic.

PMID- 30105141
TI  - Hangman's fracture surgical management with posterior C2-4 fusion: Case
      description and literature review.
AB  - Background: Hangman's fractures of the C2 verebrae represent approximately 20% of
      all cervical fractures. They are challenging cases and there is still no
      consensus regarding the optimal surgical vs nonoperative treatment. Case
      Description: A 40-year-old female presented with a C2 bilateral pars articularis
      fracture. She exhibited a partial spastic quadriparesis. Computed tomography and
      magnetic resonance imaging showed a C2 "hangman's" fracture with compromise of
      the C2-3 intervertebral disk. Adequate reduction of the fracture and subaxial
      stabilization were achieved utilizing C2 transarticular and C3-4 transfacet
      screws. Conclusions: The optimal management of unstable hangman's fractures
      remains controversial. They represent challenging cases, and new treatment
      options are available. Here, we successfully utilized a C2 transarticular and C3
      4 transfacet screw fusion without neurological sequelae.

PMID- 30105140
TI  - Adjuvant radiotherapy and outcomes of presumed hemorrhagic melanoma brain
      metastases without malignant cells.
AB  - Background: Patients with melanoma can present with a hemorrhagic intracranial
      lesion. Upon resection, pathology reports may not detect any malignant cells.
      However, the hemorrhage may obscure their presence and so physicians may still
      decide whether adjuvant radiotherapy should be applied. Here, we report on the
      outcomes of a series of patients with melanoma with hemorrhagic brain lesions
      that returned with no tumor cells. Methods: All melanoma patients who had
      craniotomies from 2008 to 2017 at a single institution for hemorrhagic brain
      lesions were identified through retrospective chart review. Those who had
      pathology reports with no malignant cells were analyzed. Recurrence at the former
      site of hemorrhage and resection was the primary outcome. Results: Ten patients
      met inclusion criteria, and the median follow-up time was 8.5 (1.8-27.3) months.
      At the time of craniotomy, the median number of brain lesions was 3 (1-25). Two
      patients had prior craniotomies, eight had prior radiation, and six had prior
      immunotherapy to the lesion of interest. After surgery, one patient received
      stereotactic radiosurgery (SRS) to the resection bed. Only one patient developed
      subsequent melanoma at the resection site; this patient developed the lesion
      recurrence once and had not received postoperative SRS. Conclusion: Although
      small foci of metastatic disease as a source of bleeding for some patients cannot
      be excluded, melanoma patients with a suspected hemorrhagic brain metastasis that
      shows no tumor cells on pathology may benefit from close observation. The local
      recurrence risk in such cases appears to be low, even without adjuvant radiation.

PMID- 30105142
TI  - Unique case of trigeminal neuralgia due to Epstein-Barr-virus-associated B-cell
      lymphomatoid granulomatosis of the Meckel's cave and cavernous sinus: Important
      clinical and therapeutic implications.
AB  - Background: Trigeminal neuralgia (TN) represents one of the most disabling pain
      syndromes. Several diseases have been described as etiological triggers of TN,
      vascular compression of the trigeminal nerve being the most frequent cause. Here,
      we describe for the first time a rare case of TN caused by an infiltration of an
      isolated Epstein-Barr virus (EBV) B-cell lymphomatoid granulomatosis (LYG) mass
      into the Meckel's cave and cavernous sinus. Case Description: A 51-year-old woman
      undergoing immunosuppressant treatment for Crohn's disease presented due to right
      sided TN. Magnetic resonance imaging (MRI) scans revealed an isolated lesion
      affecting the right Meckel's cave and lateral wall of the cavernous sinus. We
      accomplished tumor resection through a subtemporal extradural approach and the
      patient recovered successfully from surgery. Histological examination revealed an
      LYG, and a blood test confirmed low but positive EBV counts. The
      immunosuppressant therapy was discontinued and we assumed a watchful waiting
      management. During a 41-months' follow-up there was neither evidence of LYG
      recurrence nor an increase of EBV counts. Conclusions: LYG, an angiodestructive
      disease associated with EBV reactivation in the context of immune dysfunction and
      often associated with an aggressive behavior or even malignant transformation,
      should be considered as a rare differential diagnosis of TN associated with skull
      base lesions. The management of this rare disease is still controversial and
      varies from limiting the treatment to correcting immune dysfunction up to
      chemotherapy. In this case of an isolated mass, surgical excision and
      discontinuation of immunosuppressants were effective to prevent the relapse of
      the disease in a long-term follow-up.

PMID- 30105143
TI  - Intraventricular metastasis mimicking meningioma.

PMID- 30105145
TI  - Diploic mature teratoma originating from the orbital roof: An extremely rare case
      report.
AB  - Background: Orbital mature teratoma is a rare congenital tumor. Case Description:
      A 37-year-old woman presented with ophthalmalgia predated by years of progressive
      incongruous right eye position, diplopia, and restricted extraocular movement.
      Neuroimages revealed a right orbital mass originating from the orbital roof.
      After resection, histopathology revealed the mature teratoma. Conclusion: To the
      authors' best knowledge, this is the first documented diploic origin of mature
      teratoma at the orbital roof.

PMID- 30105147
TI  - Providing patient-centered care in the digital era.

PMID- 30105146
TI  - Definitions and treatments for chiari-1 malformations and its variants: Focused
      review.
AB  - Background: Reviewing the neurosurgical literature demonstrated that spinal
      neurosurgeons rarely (0.78%) diagnose chiari-1 malformation (CM-1) in adults on
      magnetic resonance (MR) studies defined by tonsillar descent >5 mm below the
      foramen magnum (FM). Children, averaging 10 years of age, exhibit CM-1 in
      96/100,000 cases. According to the literature, fewer spinal neurosurgeons
      additionally recognize and treat the low lying cerebellar tonsil (LLCT) syndrome.
      Methods: The normal location of the cerebellar tonsils on cranial/cervical MR
      averages 2.9 mm +/- 3.4 mm above or up to 3 mm below the FM. The neurosurgical
      literature revealed that most neurosurgeons diagnose and treat CM-1 where the
      tonsils are >5 mm to an average of 12 mm below the FM. Fewer spinal neurosurgeons
      additionally diagnose and treat the LLCT syndrome defined by <5 mm of tonsillar
      descent below the FM. Results: According to the neurosurgical literature, many
      neurosurgeons perform cranial/spinal decompression with/without fusion and/or
      duraplasty for CM-1. Fewer neurosurgeons perform these procedures for CM-1 and
      the LLCT syndrome, for which they additionally perform preoperative cervical
      traction under anesthesia, and the postoperative placement of occipital
      neurostimulators (ONS) for intractable headaches following chiari-1/LLCT surgery.
      Conclusion: Reviewing the literature revealed that spinal neurosurgeons rarely
      diagnose CM-1, and treat them with decompressions with/without fusions and/or
      duraplasty. Fewer spinal neurosurgeons diagnose/treat both the CM-1 and LLCT
      syndromes, perform preoperative traction under anesthesia, and place ONS for
      persistent headaches following CM-1 surgery.

PMID- 30105148
TI  - Author response: Medical retirement from sport after concussions: A practical
      guide for a difficult discussion.

PMID- 30105149
TI  - Reader response: Medical retirement from sport after concussions: A practical
      guide for a difficult discussion.

PMID- 30105144
TI  - The role of inflammation and potential use of sex steroids in intracranial
      aneurysms and subarachnoid hemorrhage.
AB  - Background: Aneurysmal subarachnoid hemorrhage (aSAH) continues to be a
      devastating neurological condition with a high risk of associated morbidity and
      mortality. Inflammation has been shown to increase the risk of complications
      associated with aSAH such as vasospasm and brain injury in animal models and
      humans. The goal of this review is to discuss the inflammatory mechanisms of
      aneurysm formation, rupture and vasospasm and explore the role of sex hormones in
      the inflammatory response to aSAH. Methods: A literature review was performed
      using PubMed using the following search terms: "intracranial aneurysm," "cerebral
      aneurysm," "dihydroepiandrosterone sulfate" "estrogen," "hormone replacement
      therapy," "inflammation," "oral contraceptive," "progesterone," "sex steroids,"
      "sex hormones" "subarachnoid hemorrhage," "testosterone." Only studies published
      in English language were included in the review. Results: Studies have shown that
      administration of sex hormones such as progesterone and estrogen at early stages
      in the inflammatory cascade can lower the risk and magnitude of subsequent
      complications. The exact mechanism by which these hormones act on the brain, as
      well as their role in the inflammatory cascade is not fully understood. Moreover,
      conflicting results have been published on the effect of hormone replacement
      therapy in humans. This review will scrutinize the variations in these studies to
      provide a more detailed understanding of sex hormones as potential therapeutic
      agents for intracranial aneurysms and aSAH. Conclusion: Inflammation may play a
      role in the pathogenesis of intracranial aneurysm formation and subarachnoid
      hemorrhage, and administration of sex hormones as anti-inflammatory agents has
      been associated with improved functional outcome in experimental models. Further
      studies are needed to determine the therapeutic role of these hormones in the
      intracranial aneurysms and aSAH.

PMID- 30105150
TI  - Reader response: Incorporating students into clinic may be associated with both
      improved clinical productivity and educational value.

PMID- 30105151
TI  - Author response: Incorporating students into clinic may be associated with both
      improved clinical productivity and educational value.

PMID- 30105152
TI  - Author response: Pimavanserin: A novel therapeutic option for Parkinson disease
      psychosis.

PMID- 30105153
TI  - Reader response: Pimavanserin: A novel therapeutic option for Parkinson disease
      psychosis.

PMID- 30105154
TI  - Curbside consults join the telemedicine era.

PMID- 30105156
TI  - Erratum: Apathy and functional disability in behavioral variant frontotemporal
      dementia.
AB  - [This corrects the article on p. 120 in vol. 8, PMID: 29708208.].

PMID- 30105155
TI  - Identifying priority outcomes that influence selection of disease-modifying
      therapies in MS.
AB  - Background: Persons with multiple sclerosis (MS) may now choose from a broad
      array of approved disease-modifying treatments (DMTs). The priority that patients
      and practitioners assign to specific clinical outcomes is likely to influence the
      MS DMT selection process. Methods: We invited 9,126 participants in the North
      American Research Committee on Multiple Sclerosis (NARCOMS) Registry and 18
      members of the American Academy of Neurology MS DMT guideline development panel
      to complete a brief survey prioritizing outcomes of importance to MS DMT
      selection. The frequency of outcomes ranked as first, second, or third priority
      by respondents were compared across groups. Results: A total of 2,056 of 9,126
      (23.6%) NARCOMS participants and all 18 members of the MS DMT guideline
      development panel (100%) completed the survey. Reduced disability progression was
      identified as a priority by a majority of respondents in both groups. Guideline
      panelists tended to be more likely than persons with MS to prioritize relapse
      rate reduction (p = 0.055). Respondents from both groups commonly cited the
      "selection of therapies most likely to lead to improvements in quality of life
      measures, MS symptoms, and preservation of cognition" as top priorities in DMT
      selection; however, these priority outcomes were reported in fewer than 20% of
      clinical trials used to inform MS DMT guideline development. Conclusion: Specific
      outcomes were defined by similar proportions of persons with MS and guideline
      panelists as priority outcomes influencing MS DMT selection. Several of these
      priority outcomes were not routinely reported in clinical trials, identifying
      areas for future evidence development.

PMID- 30105157
TI  - Ask a neurologist: What primary care providers ask, and reducing referrals
      through eConsults.
AB  - Background: Access to neurology consultation is limited by high demand and
      urgency of the presentation. Champlain BASETM (Building Access to Specialists
      through eConsultation) (eConsult service) aims to increase access through direct
      communication between primary care providers (PCPs) and specialists. Rapid
      responses to PCP questions can guide management and sometimes relieve the need
      for a formal consultation. We reviewed which topics were frequently addressed,
      the types of questions asked, and the effect on primary care for the patient.
      Methods: This is a retrospective review of 387 consecutive questions submitted to
      the Champlain BASETM service between May 2011 and January 2015 and the data
      generated from routine use and PCP exit surveys. Questions were categorized by
      topic and type and analyzed quantitatively. This included time required to answer
      each question and effect on plans for traditional referral and clinical course of
      action. Results: The top 5 topics were headache (17%), incidental imaging
      findings (11%), numbness/tingling (11%), seizure (9%), and cerebrovascular
      disease (CVD) (9%). Fifty-one percent were related to diagnosis (choice of test,
      imaging interpretation, symptom interpretation), 23% to drug treatment (choice,
      adverse effects, prescribing instructions), and 17% to management (general, need
      for referral). Eighty-eight percent of questions took less than 10 minutes of
      specialist time to answer, and 80% were answered within 1 day. eConsults
      decreased face-to-face referrals by 50%. In 54% of cases, the PCP received
      information for a new course of action. Conclusions: We found that an eConsult
      service provides timely access to neurologists and can divert half of intended
      face-to-face consultations. The most common questions posed by PCPs regarded
      diagnosis and drug therapy for headaches, seizures, altered sensation, and CVD.
      eConsult services could provide guidance for continuing medical education
      planning in neurology.

PMID- 30105158
TI  - Receipt of cardiac screening does not influence 1-year post-cerebrovascular event
      mortality.
AB  - Background: American Heart Association/American Stroke Association expert
      consensus guidelines recommend consideration of cardiac stress testing to screen
      for occult coronary heart disease (CHD) among patients with ischemic stroke/TIA
      who have a high-risk Framingham Cardiac Risk Score (FCRS). Whether this guideline
      is being implemented in routine clinical practice, and the association of its
      implementation with mortality, is less clear. Methods: Study participants were
      Veterans with stroke/TIA (n = 11,306) during fiscal year 2011 who presented to a
      VA Emergency Department or who were admitted. Patients were excluded (n = 6,915)
      based on prior CHD/angina/chest pain history, receipt of cardiac stress testing
      within 18 months prior to cerebrovascular event, death within 90 days of
      discharge, discharge to hospice, transfer to a non-VA acute care facility, or
      missing/unknown race. FCRS >=20% was classified as high risk for CHD. ICD-9 and
      Common Procedural Terminology codes were used to identify receipt of any cardiac
      stress testing. Results: Among 4,391 eligible patients, 62.8% (n = 2,759) had
      FCRS >=20%. Cardiac stress testing was performed infrequently and in similar
      proportion among high-risk (4.5% [123/2,759]) vs low/intermediate-risk (4.4%
      [72/1,632]) patients (adjusted odds ratio [aOR] 0.77, 95% confidence interval
      [CI] 0.54-1.10). Receipt of stress testing was not associated with reduced 1-year
      mortality (aOR 0.59, CI 0.26-1.30). Conclusions: In this observational cohort
      study of patients with cerebrovascular disease, cardiac screening was relatively
      uncommon and was not associated with 1-year mortality. Additional work is needed
      to understand the utility of CHD screening among high-risk patients with
      cerebrovascular disease.

PMID- 30105159
TI  - Clinical factors associated with Guillain-Barre syndrome following surgery.
AB  - Background: We sought to identify clinical associations and potential triggers of
      Guillain-Barre syndrome (GBS) within 6 weeks of surgery. Methods: We
      retrospectively reviewed consecutive patients diagnosed with GBS within 6 weeks
      of a surgery between January 1995 and June 2014 at Mayo Clinic. Postsurgical GBS
      was defined as symptom onset within 6 weeks of surgery. Patients with
      postsurgical GBS were compared with patients who did not have a surgery prior to
      GBS onset to determine differences between groups. Results: A total of 208
      patients with GBS, median age 55 years (interquartile range [IQR] 41-68), were
      included. Nineteen patients (9.1%) developed postsurgical GBS. Median duration
      from the surgery to onset of first GBS symptom was 15 days (IQR 9-37). The main
      types of surgeries preceding GBS were gastrointestinal, orthopedic, and cardiac.
      General anesthesia was used in 18 (95%) and conscious sedation in 1 (5%) patient.
      Among the 19 patients with postsurgical GBS, 11 (57.9%) had a known diagnosis of
      malignancy. Autoimmune conditions were present in 5 (26.3%) patients.
      Postoperative infection was found in 4 (21%) patients. On univariate analysis,
      the factors that showed an association with postsurgical GBS were age (p = 0.02),
      malignancy (p <= 0.0004), active malignancy (p = 0.03), preexisting autoimmune
      disorder (p = 0.02), and infection (p = 0.0001). On multivariate analysis, only
      active malignancy (0.03) remained associated. Conclusions: Surgery antedated GBS
      in 9.1% of patients. Postsurgical GBS was more common in patients with an active
      malignancy. A prospective study is needed to determine whether active malignancy
      represents an independent risk factor for the development of postsurgical GBS.

PMID- 30105160
TI  - Neuroimaging abnormalities in patients with Cowden syndrome: Retrospective single
      center study.
AB  - Background: We retrospectively reviewed the neuroimaging findings of patients
      with Cowden syndrome and determined their frequency in a single cohort. Methods:
      Electronic medical records were queried from January 1999 to January 2017 to
      identify patients who fit the clinical criteria for diagnosis of Cowden syndrome
      with or without a documented PTEN mutation. Patients with brain MRI examinations
      were then identified. Results: We retrospectively identified 44 patients with
      Cowden syndrome, 22 of whom had neuroimaging for review. Eleven (50%) had
      Lhermitte-Duclos disease, 4 (18.1%) had meningiomas, 13 (59.1%) had at least one
      developmental venous anomaly, 3 had cavernous malformations, 2 had evidence of
      dural arteriovenous fistula, 7 had increased white matter signal abnormalities
      relative to age (31.8%), 4 had prominent perivascular spaces, cerebellar
      tonsillar ectopia was present in 7 of 21 (33.3%), and 1 had cortical
      malformation. Conclusions: It is important to recognize that in addition to
      Lhermitte-Duclos disease, other intracranial findings such as multiple venous
      anomalies, meningiomas, greater than expected white matter signal abnormality,
      prominent perivascular spaces, and cortical malformations may warrant a thorough
      evaluation for Cowden syndrome in the appropriate clinical setting. We further
      recommend that this broader spectrum of intracranial abnormalities be considered
      for addition to the Cowden syndrome diagnostic criteria at the time of next
      revision.

PMID- 30105161
TI  - What predicts falls in Parkinson disease?: Observations from the Parkinson's
      Foundation registry.
AB  - Background: We undertook this study to identify patients with Parkinson disease
      (PD) with no or rare falls who may progress to frequent falling by their next
      annual follow-up visit. Methods: We analyzed data in the National Parkinson
      Foundation Quality Improvement Initiative database to identify factors predicting
      which patients with PD with no or rare falls at the baseline visit will report at
      least monthly falls at the annual follow-up visit. Multivariable models were
      constructed using logistic regression. Variables were introduced in 4 blocks: in
      the 1st block, variables present at or before the baseline visit were entered; in
      the 2nd, baseline visit assessments; in the 3rd, interventions implemented during
      baseline visit; and, in the 4th block, changes in comorbidities, living
      situation, and treatment between visits. Results: Of 3,795 eligible participants,
      3,276 (86.3%) reported no or rare falls at baseline visit, and of them, 382
      (11.7%) reported at least monthly falls at follow-up visit. Predictors included
      female sex, <90% diagnostic certainty, motor fluctuations, levodopa treatment,
      antidepressant treatment, prior deep brain stimulation (DBS), worse quality of
      life, Hoehn & Yahr stage 2 or 3, worse semantic fluency, and, between visits,
      addition of amantadine, referral to occupational therapy, social services, or
      DBS, new diagnoses of cancer or osteoarthritis, and increased emergency visits.
      Conclusions: This large-scale analysis identified several predictors of
      progression to falling in PD. Such identifiers may help target patient subgroups
      for falls prevention intervention. Some factors are modifiable, offering
      opportunities for developing such interventions.

PMID- 30105162
TI  - Prevalence of and risk factors for cerebral microbleeds in a general Japanese
      elderly community.
AB  - Background: We investigated the prevalence of and risk factors for cerebral
      microbleeds (CMBs) in a cross-sectional study of a general population of Japanese
      elderly. Methods: In 2012, brain MRI scanning at 1.5T and comprehensive health
      examination were conducted for 1281 residents aged 65 years or older. CMBs were
      defined as ovoid hypointensity lesions less than 10 mm in diameter on T2*
      weighted images and classified into deep/infratentorial or lobar CMBs. Age- and
      sex-specific and overall prevalence of CMBs were estimated, and the associations
      of traditional cardiovascular risk factors and APOE polymorphism with the
      presence of CMBs were examined using a logistic regression analysis. Results: The
      crude prevalences of total, deep/infratentorial, and lobar CMBs were 18.7% (n =
      240), 13.5% (n = 173), and 9.6% (n = 123), respectively. The prevalence of total
      CMBs was 23.0% in men and 15.5% in women and increased with aging in both sexes
      (both p for trend <0.01). Hypertension was significantly associated with the
      presence of both deep/infratentorial and lobar CMBs. Lower serum total
      cholesterol was a significant risk factor for deep/infratentorial CMBs, but not
      for lobar CMBs, while APOE epsilon4 carriers had a significantly higher
      likelihood only of lobar CMBs compared with noncarriers. Conclusions: Our study
      suggests that approximately 1 of 5 Japanese elderly people have CMBs, and that
      risk factors for deep/infratentorial and lobar CMBs are different, indicating the
      distinct pathologic backgrounds of these lesions.

PMID- 30105163
TI  - Reflections on translation: Views of participants in a multisite Canadian CCSVI
      clinical trial.
AB  - Background: We sought to characterize the perspectives of participants in
      Canada's phase I/II chronic cerebrospinal venous insufficiency (CCSVI) clinical
      trial prior to and after the disclosure of trial results. Methods: This was a
      researcher-administered survey of individuals who participated in Canada's CCSVI
      trial (Clincialtrials.gov, NCT01864941) about their (1) motivations for
      participating, (2) understanding of the trial process, and (3) perspectives on
      the social value of the trial. Results: A total of 63 participants completed the
      survey. Participants were motivated to participate by altruism (mean score = 4.56
      out of 5) and a desire to access the intervention in Canada (mean score = 3.63
      out of 5). Many participants expected medical benefits, such as partial disease
      reversal (mean score = 3.32 out of 5). Participants felt strongly that the
      crossover trial design promoted fairness (mean score = 4.65 out of 5).
      Participants' familiarity with the CCSVI controversy increased significantly
      after the results were revealed (p = 0.0001). Despite negative trial results,
      participants still felt that the trial was an appropriate use of tax dollars
      (mean score = 4.68 out of 5). Many (38%) upheld the belief that further CCSVI
      research is necessary (responses of 4 out of 5 or higher). Conclusions: There is
      a strong movement in science today to ensure that research agendas reflect the
      perspectives of multiple stakeholders, including research participants. While
      previous work suggests that negative findings adversely affect trust in science,
      the perspectives of participants in this study demonstrate that good trial design
      and resilience can prevail over expected tensions.

PMID- 30105164
TI  - Camptocormia: Etiology, diagnosis, and treatment response.
AB  - Background: We sought to determine the etiologies, diagnostic testing, and
      management of a retrospective cohort of patients with camptocormia evaluated at a
      single center. Methods: We reviewed medical records of all adult patients
      evaluated at Mayo Clinic Rochester with a diagnosis of camptocormia from 2000 to
      2014. Demographic and clinical data were abstracted and analyzed. Results: There
      were 276 patients (58.0% male), with mean age at presentation of 68.6 (+/-12.7)
      years. An etiology was identified in 98.2%. The most common etiologies were
      idiopathic Parkinson disease (22.5%), idiopathic axial myopathy (14.1%), and
      degenerative joint disease without fixed deformity (13.0%). We also identified
      several rare causes of camptocormia. Investigations included spine imaging,
      needle and surface EMG, and muscle biopsy. Most patients received physical
      therapy and orthotic support with limited benefit. Limited improvement of
      camptocormia was seen where a treatable etiology was identified. Conclusions: An
      etiology can be identified in almost all cases of camptocormia. Most cases are
      due to 3 common disorders: Parkinson disease, axial myopathy, and degenerative
      joint disease. A diagnostic and treatment algorithm is proposed.

PMID- 30105165
TI  - Early myoclonus following anoxic brain injury.
AB  - Background: It is unknown whether postanoxic cortical and subcortical myoclonus
      are distinct entities with different prognoses. Methods: In this retrospective
      cohort study of 604 adult survivors of cardiac arrest over 8.5 years, we
      identified 111 (18%) patients with myoclonus. Basic demographics and clinical
      characteristics of myoclonus were collected. EEG reports, and, when available,
      raw video EEG, were reviewed, and all findings adjudicated by 3 authors blinded
      to outcomes. Myoclonus was classified as cortical if there was a preceding, time
      locked electrographic correlate and otherwise as subcortical. Outcome at
      discharge was determined using Cerebral Performance Category. Results: Patients
      with myoclonus had longer arrests with less favorable characteristics compared to
      patients without myoclonus. Cortical myoclonus occurred twice as often as
      subcortical myoclonus (59% vs 23%, respectively). Clinical characteristics during
      hospitalization did not distinguish the two. Rates of electrographic seizures
      were higher in patients with cortical myoclonus (43%, vs 8% with subcortical).
      Survival to discharge was worse for patients with myoclonus compared to those
      without (26% vs 39%, respectively), but did not differ between subcortical and
      cortical myoclonus (24% and 26%, respectively). Patients with cortical myoclonus
      were more likely to be discharged in a comatose state than those with subcortical
      myoclonus (82% vs 33%, respectively). Among survivors, good functional outcome at
      discharge was equally possible between those with cortical and subcortical
      myoclonus (12% and 16%, respectively). Conclusions: Cortical and subcortical
      myoclonus are seen in every sixth patient with cardiac arrest and cannot be
      distinguished using clinical criteria. Either condition may have good functional
      outcomes.

PMID- 30105166
TI  - Exercise for cognitive brain health in aging: A systematic review for an
      evaluation of dose.
AB  - Purpose of review: We systematically appraised randomized controlled trials
      proposing exercise to influence cognition in older adults to (1) assess the
      methodologic quality using Cochrane criteria; (2) describe various exercise dose
      measures and assess their relationship with improved cognitive performance; and
      (3) identify consistent patterns of reported effects on cognition. Recent
      findings: There was overall good methodologic quality in all 98 included studies.
      The assessment of the relationship between improved cognition and various
      measures of exercise dose (session duration, weekly minutes, frequency, total
      weeks, and total hours) revealed a significant correlation with total hours.
      Improvements in global cognition, processing speed/attention, and executive
      function were most stable and consistent. Summary: We found that exercising for
      at least 52 hours is associated with improved cognitive performance in older
      adults with and without cognitive impairment. Exercise modes supported by
      evidence are aerobic, resistance (strength) training, mind-body exercises, or
      combinations of these interventions.

PMID- 30105167
TI  - Practice Current: When do you order ancillary tests to determine brain death?
AB  - Brain death has been accepted as a legal definition of death in most countries,
      but practices for determining brain death vary widely. One source of variation is
      in the use of ancillary tests to assist in the diagnosis of brain death. Through
      case-based discussions with 3 experts from 3 continents, this article discusses
      selected aspects of brain death, with a focus on the use of ancillary tests. In
      particular, we explore the following questions: Are ancillary tests necessary, or
      is the clinical examination sufficient? What ancillary tests are preferred, and
      under which circumstances? Are ancillary tests required when the primary
      mechanism of injury is brainstem injury? Should the family's wishes play a role
      in the need for ancillary tests? The same case-based questions were posed to the
      rest of our readership in an online survey, the preliminary results of which are
      also presented.

PMID- 30105168
TI  - Chronic ambulatory electrocorticography findings preceding sudden death in
      epilepsy.

PMID- 30105169
TI  - Papillary fibroelastoma, an unexpected cause of stroke: Outcomes after acute
      reperfusion therapy.

PMID- 30105171
TI  - Jack-o'-lantern sign in dengue encephalitis.

PMID- 30105170
TI  - EEG registration during ventricular tachycardia and resuscitation.

PMID- 30105172
TI  - Progressive multifocal leukoencephalopathy with extended natalizumab dosing.

PMID- 30105173
TI  - Multifocal stroke with proliferation of small cerebral arteries in
      hepatopulmonary syndrome.

PMID- 30105174
TI  - Correction: Pancreatic Cancer: Feasibility and Outcome After Radiochemotherapy
      with High Dose External Radiotherapy for Non-resected and R1 Resected Patients.
AB  - [This corrects the article DOI: 10.7759/cureus.2713.].

PMID- 30105176
TI  - Earthworm individualities when facing a conflict between turn alternation and
      aversive learning.
AB  - An individual's personality develops through a combination of experiences and
      parental inheritance. When faced with a conflict, will an individual take an
      innate behavior or a learned one? In such situations, individuality will manifest
      itself. Here, we focused on turn alternation behavior, which is a habitual
      tendency to turn in the direction opposite the preceding turn, in earthworms
      (Eisenia fetida) and examined how this behavior is affected by an aversive
      stimulus. Of 10 earthworms, 3 were affected by the stimulus. Turn alternation
      deteriorated in two worms, one of which showed anti-turn alternation behavior,
      whereas the remaining worm showed an enhanced tendency toward turn alternation.
      Earthworms have a relatively simple nervous system. This study opens the door to
      investigate the neuronal basis for individuality that emerges between nature and
      nurture.

PMID- 30105175
TI  - My various thoughts on actin.
AB  - An enormous amount of research has been performed to characterize actin dynamics.
      Structural biology investigations have determined the localization of main chains
      and their changes coupled with G (Globular)-F (Filamentous) transformation of
      actin, whereas local thermal fluctuations that may be caused by free rotations of
      the tips of side chains are not yet fully investigated. This paper argues if the
      entropy change of actin accompanied by the G-F transformation is simply
      attributable to the changes in hydration. It took almost 10 years to understand
      that the actin filament is semi-flexible. This flexibility was visually confirmed
      as the development of optical microscope techniques, and the direct observation
      of actin severing events in the presence of actin binding proteins became
      possible. Finally, I expect the deep understanding of actin dynamics will lead to
      the elucidation of self-assembly mechanisms of the living creature.

PMID- 30105177
TI  - Cloning and characterization of trehalase: a conserved glycosidase from oriental
      midge, Chironomus ramosus.
AB  - Insect trehalase is a multiferous enzyme, crucial for normal physiological
      functions as well as under stress conditions. In this report, we present a
      fundamental study of the trehalase gene segment (1587 bp) from Chironomus ramosus
      (CrTre) encoding for 529 amino acids, using appropriate bioinformatics tools. C.
      ramosus, a tropical midge is an emerging animal model to investigate the
      consequences of environmental stresses. We observed that CrTre belongs to GH
      family 37 in the CAZy database and possess 57-92% identity to dipteran
      trehalases. In silico characterization provided information regarding the
      structural, functional and evolutionary aspects of midge trehalase. In the
      phylogenetic tree, CrTre clustered with the soluble dipteran trehalases.
      Moreover, domain functional characterization of the deduced protein sequence by
      InterProScan (IPR001661), ProSite (PS00927 and PS00928) and Pfam (PF01204)
      indicated presence of highly conserved signature motifs which are important for
      the identification of trehalase superfamily. Furthermore, the instability index
      of CrTre was predicted to be < 40 suggesting its in vivo stability while, the
      high aliphatic index indicated towards its thermal stability (index value 71-81).
      The modelled 3D tertiary structure of CrTre depicts a (alpha/alpha)6 barrel
      toroidal core. The catalytic domain of the enzyme comprised Glu424 and Asp226 as
      the putative active site residues. Interestingly, the conserved motifs were
      observed to be formed by the flexible loopy regions in the tertiary structure.
      This study revealed essential sequence features of the midge trehalase and offers
      better insights into the structural aspects of this enzyme which can be
      correlated with its function.

PMID- 30105178
TI  - High sequence variation in the exon 10 of TSHR gene is associated with flightless
      domestic geese.
AB  - The genetic and molecular mechanisms of the flightless birds without limb
      modification are rarely reported. To explore the possible reasons for losing
      flight ability without limb modification, we used the domestic geese as an ideal
      model to preliminarily study the possible mechanisms for this kind of
      flightlessness. We compared the sequence variations of the exon 10 of TSHR gene
      between three domesticated geese populations and two wild ancestor populations.
      The results showed that domestic geese had higher genetic diversity and more
      complex population structure than their wild ancestors. We did not detect any
      population expansion in domestic geese population. However, we detected clear
      relaxed selection signal and positive selection in domesticated geese groups.
      Furthermore, special phylogenetic relationship of the exon 10 of TSHR was
      observed in domesticated geese groups. Combined with its well-established
      function on metabolic regulation and photoperiod control, we speculate that
      relaxed selection of TSHR might have effects on flightlessness of domesticated
      geese.

PMID- 30105179
TI  - A simple and inexpensive physical lysis method for DNA and RNA extraction from
      freshwater microalgae.
AB  - In this work, a simple and inexpensive physical lysis method using a cordless
      drill fitted with a plastic pellet pestle and 150 mg of sterile sea sand was
      established for the extraction of DNA from six strains of freshwater microalgae.
      This lysis method was also tested for RNA extraction from two microalgal strains.
      Lysis duration between 15 and 120 s using the cetyltrimethyl ammonium bromide
      (CTAB) buffer significantly increased the yield of DNA from four
      microalgalstrains (Monoraphidium griffithii NS16, Scenedesmus sp. NS6,
      Scenedesmus sp. DPBC1 and Acutodesmus sp. DPBB10) compared to control. It was
      also found that grinding was not required to obtain DNA from two strains of
      microalgae (Choricystis sp. NPA14 and Chlamydomonas sp. BM3). The average DNA
      yield obtained using this lysis method was between 62.5 and 78.9 ng/mg for M.
      griffithii NS16, 42.2-247.0 ng/mg for Scenedesmus sp. NS6, 70.2-110.9 ng/mg for
      Scenedesmus sp. DPBC1 and 142.8-164.8 ng/mg for Acutodesmus sp. DPBB10. DNA
      obtained using this method was sufficiently pure for PCR amplification.
      Extraction of total RNA from M. griffithii NS16 and Mychonastes sp. NPD7 using
      this lysis method yielded high-quality RNA suitable for RT-PCR. This lysis method
      is simple, cheap and would enable rapid nucleic acid extraction from freshwater
      microalgae without requiring costly materials and equipment such as liquid
      nitrogen or beadbeaters, and would facilitate molecular studies on microalgae in
      general.

PMID- 30105180
TI  - Exploring the genetic variations and population structure of Turkish pepper
      (Capsicum annuum L.) genotypes based on peroxidase gene markers.
AB  - Capsicum is thought as one of the most diverse and significant genera due to its
      varied uses in different parts of the world. In this study, we worked with a
      total of 71 pepper genotypes from different locations of Turkey to investigate
      the level of their diversity using the peroxidase gene polymorphism (POGP)
      markers to reveal their population structure. For this purpose, 14 peroxidase
      primer pairs were used. They produced 139 bands (mean = 9.9 bands/primer), of
      which ~ 85.6% were polymorphic in the all germplasm collection. Polymorphism
      information content (PIC) ranged between 0.48 and 0.97 with an average of 0.75.
      Range and mean values for gene diversity (h) were 0.09-0.22 and 0.17,
      respectively. Shannon's information index (I) per POGP marker ranged from 0.18 to
      0.35 with a mean of 0.29. Using three clustering methods (unweighted pair-group
      method with arithmetic means, principal coordinate analysis, and STRUCTURE)
      revealed a clear separation of all the C. annuum accessions from C. frutescens
      and C. chinense accessions in our study. Clusters did not establish an
      association between the accessions and their geographical origin. This is the
      first study exploring the population structure through the genetic diversity of
      Turkish peppers from different regions of the country based on the peroxidase
      gene markers.

PMID- 30105182
TI  - Genetic diversity of Chilli veinal mottle virus infecting different chilli
      landraces in North East India indicates the possibility of transboundary movement
      of virus.
AB  - Diverse chilli genetic resources of North East India occupy a unique niche in the
      Nation's chilli gene pool. Widely cultivated chilli landraces (King chilli:
      Capsicum chinense, bird eye chilli: Capsicum frutescens and Capsicum annuum) of
      North East India in general and Manipur in particular suffer from decline complex
      due to high incidence of viral diseases. With this background and the known
      prominent distribution of Chilli veinal mottle virus (ChiVMV) in Asian region, we
      studied its prevalence and association with diverse symptoms of chilli landraces.
      Molecular indexing of samples from 40 chilli plantation groves of Manipur using
      reverse transcription (RT)-PCR targeting the coat protein (CP) region of ChiVMV
      genome revealed a high incidence and wide prevalence. Out of a total of 127
      chilli samples collected from different groves of Manipur, 81 chilli samples
      (63.78%) were positive for ChiVMV. Interestingly, ChiVMV infection rate was
      comparatively higher in the hilly groves (69.23% samples positive) compared to
      the valley groves (60% samples positive). Present study through the extensive
      surveys and molecular indexing work, conclusively reported the association of
      ChiVMV with diverse symptoms like cupping of leaf lamina with mottling, vein
      banding and puckering in different chilli landraces. Further, five representative
      ChiVMV isolates sampled from different groves of Manipur upon mechanical
      inoculation showed significant variation in symptom expression, indicating wide
      pathogenic diversity among them. Partial coat protein (CP) sequence analysis of
      five ChiVMV isolates from Manipur although indicated genetic homogeneity among
      them, but distinctiveness from ChiVMV isolates reported from the other parts of
      India. Phylogenetic clustering of ChiVMV isolates from Manipur near Chinese
      isolates rather than other Indian isolates suggested the possibility of
      transboundary movement.

PMID- 30105181
TI  - Influence of media supplements on inhibition of oxidative browning and bacterial
      endophytes of Camellia sinensis var. sinensis.
AB  - Explant oxidative browning and necrosis of Camellia sinensis var. sinensis is a
      severe problem in tissue culture, often associated with the exuded phenolic
      compounds and microbial contamination from the explants. In this study, 2
      aminoindane-2-phosphonic acid (AIP), an inhibitor of the polyphenol production
      required enzyme phenylalanine ammonia lyase (PAL), and different antibiotics were
      tested to control tea explant necrosis and browning. These compounds were
      supplemented in the regular plant growth medium together with 6-benzylaminopurine
      and thidiazuron at different concentrations. Our data indicated that application
      of 2 uM of AIP was able to effectively inhibit callus browning, significantly
      reduce EGC abundance, and greatly improve callus induction and growth. Moreover,
      the use of 150 mg/L of timentin and 30 mg/L gentamycin resulted in an effective
      elimination of the surface and endophytic microbes associated with explants of C.
      sinensis var. sinensis. Our study revealed that the inhibition of PAL using AIP
      combined with the two tested antibiotics could open up new doors to control
      oxidative tissue browning and endophyte contamination in tissue culture for tea
      genetic manipulation.

PMID- 30105183
TI  - Futuristic biosensors for cardiac health care: an artificial intelligence
      approach.
AB  - Biosensor-based devices are pioneering in the modern biomedical applications and
      will be the future of cardiac health care. The coupling of artificial
      intelligence (AI) for cardiac monitoring-based biosensors for the point of care
      (POC) diagnostics is prominently reviewed here. This review deciphers the most
      significant machine-learning algorithms for the futuristic biosensors along with
      the internet of things, computational techniques and microchip-based essential
      cardiac biomarkers for real-time health monitoring and improving patient
      compliance. The present review also discusses the recently developed cardiac
      biosensors along with technical strategies involved in their mechanism of working
      and their applications in healthcare. Additionally, it provides a key for the
      ontogeny of an effective and supportive hierarchical protocol for clinical
      decision-making about personalized medicine through combinatory information
      analysis, and integrated multidisciplinary AI approaches.

PMID- 30105184
TI  - Bioprospecting lovastatin production from a novel producer Cunninghamella
      blakesleeana.
AB  - Beside anti-cholesterol activity, lovastatin garners worldwide attention for
      therapeutical application against various diseases especially cancer. A total of
      36 filamentous fungi from soil samples were isolated and screened for lovastatin
      production by yeast growth bioassay method. C9 strain (later identified as
      Cunninghamella blakesleeana) was screened as potential strain of lovastatin
      production. Further confirmation of the compound was made using TLC, HPTLC and
      HPLC in which similar Rf value, densitogram peak and chromatogram peak against
      the standard lovastatin were observed, respectively. The purified lovastatin
      subjected for IR analysis showed a lactone ring peak at 1763.63 cm-1 similar to
      standard lovastatin. Further structural analysis including NMR and LC-MS of the
      purified lovastatin reassures the molecular formula and molecular weight similar
      to standard. In quantitative terms, C. blakesleeana, Aspergillus terreus and
      Aspergillus flavus produced 1.4 mg g-1 DWS, 0.83 mg g-1 DWS and 0.3 mg g-1 DWS of
      lovastatin, respectively, (p < 0.0001) without any optimization. Lovastatin
      showed significant antioxidant property with IC50: 145.9 ug mL-1 (140 uL), and
      the percentage of inhibition is maximum at 199.5 ug/mL which is statistically
      significant (p < 0.0001).

PMID- 30105185
TI  - Optimization of culture conditions for mass production and bio-formulation of
      Trichoderma using response surface methodology.
AB  - Use of agro-waste for production of value added products is a good alternative
      for developing low-cost carriers for formulation of Trichoderma-based bio
      products. It provides avenues for safe utilization of wastes, while reducing cost
      and environment pollution load of waste disposal. The present study was
      undertaken to find suitable agro-waste for economical and higher mass production
      of Trichoderma lixii TvR1 under solid-state fermentation, optimizing culture
      conditions using mathematical model and assessing effect of formulated bio
      product on growth of Spinach (Spinacia oleracea). Among various agro-wastes
      screened, sugarcane bagasse was observed to support maximum growth (20.08 * 107
      spores/g) of T. lixii TvR1 which was significantly (p <= 0.05) higher than the
      others. The Response Surface Methodology (RSM) was used to optimize culture
      conditions using optimal point prediction analysis which predicted that maximum
      spore production of T. lixii TvR1 (19.1245 * 107 spores/g) will be obtained at 30
      degrees C and 68.87% of moisture content after 31 days of incubation. Amendment
      of formulated bio-product of T. lixii TvR1 in soil at concentration 15% w/w
      promoted biomass, photosynthetic pigments, and protein content of spinach
      (significant at p <= 0.05). After 6 weeks of sowing the shoot length, root
      length, and photosynthetic pigments of plants irrigated daily and on alternate
      days were reported to be increased by 66.97, 185.03, and 82.80%; and 56.56,
      71.36, and 74.64%, respectively; over the no amendment.

PMID- 30105186
TI  - ADNCD: a compendious database on anti-diabetic natural compounds focusing on
      mechanism of action.
AB  - Diabetes is a deteriorating metabolic ailment which negatively affects different
      organs; however, its prime target is insulin secreting pancreatic beta-cells.
      Although, different medications have been affirmed for diabetes management and
      numerous drugs are undergoing clinical trials, no significant breakthrough has
      yet been achieved. Available drugs either show some side effects or provide only
      short-term alleviation. The rationales behind the failure of current anti
      diabetic treatment strategy are association of complex patho-physiologies and
      participation of various organs. Consequently, there is a critical need to search
      for multi-effect drugs that might impede various patho-physiological mechanisms
      related to diabetes. Fortunately, one natural compound could act on several
      diabetes linked targets. Thus, natural compounds might be regarded as a viable
      alternative choice to improve the progression as well as side effects of
      diabetes. Despite the fact that immense literatures are available on natural
      compounds indicating promising outcomes against diabetes, more systematic studies
      are still needed to establish them as effective anti-diabetic agents. Till date,
      we are unable to access all the information regarding modes of action, toxicity
      risks and physicochemical properties of anti-diabetic natural compounds on one
      platform. Hence, anti-diabetic natural compounds database (ADNCD) has been
      created to categorize each anti-diabetic natural compound on the basis of their
      mode of action and to provide compendious information of their physicochemical
      properties and toxicity risks. In short, ADNCD has imperative information for the
      researchers working in the field of diabetes drug development.

PMID- 30105188
TI  - l-Homocarnosine, l-carnosine, and anserine attenuate brain oxidative damage in a
      pentylenetetrazole-induced epilepsy model of ovariectomized rats.
AB  - In this study, we investigated the protective effect of l-homocarnosine, l
      carnosine, and anserine (HCA) on seizure-induced brain injuries. We evaluated the
      protective effect of HCA on brain oxidative damage in a pentylenetetrazole (PTZ)
      induced epilepsy model using ovariectomized (OVX) rats. The experimental groups
      were as follows: group I, sham; group II, sham + PTZ; group III, sham + HCA +
      PTZ; group IV, OVX; group V, OVZ + PTZ; and group VI, OVX + HCA + PTZ. We
      determined the levels of lipid peroxidation, glutathione peroxidase (Gpx),
      reduced glutathione (GSH), catalase, superoxide dismutase (SOD), and thiol in
      brain hippocampal and cortical tissue. The biochemical markers were significantly
      altered in the brain tissue of OVX rats. HCA supplementation significantly
      reduced lipid peroxidation and increased GSH, Gpx, SOD, catalase, and thiol
      levels in PTZ-treated OVX rats. Rats with an ovariectomy showed a significant
      protective effect against PTZ through elevation of the latency of generalized
      tonic-clonic seizures (GTCS). HCA substantially increased minimal clonic seizure
      and GTCS latency in the OVX-PTZ and sham-PTZ groups. In summary, our experimental
      data indicate that combined supplementation of HCA substantially increased
      anticonvulsant activity. Moreover, combined HCA supplementation reduced oxidative
      damage by decreasing lipid peroxidation and increasing antioxidant levels in the
      brain of a PTZ-induced seizure rodent model.

PMID- 30105187
TI  - Assessment of the effects of metal oxide nanoparticles on the growth, physiology
      and metabolic responses in in vitro grown eggplant (Solanum melongena).
AB  - Nanoparticles (NPs) are widely used in various domestic products and their usage
      is constantly increasing which in turn can raise several environmental health
      issues. Like other abiotic stresses, nanomaterials also affect the growth of crop
      plants. Solanum melongena is a common vegetable crop grown in the tropics and
      subtropics regions with medicinal properties. In this study, S. melongena was
      analyzed for its response to three commercially important metallic nanoparticles,
      namely NiO, CuO, and ZnO, at four different concentrations (100, 250, 500 and
      1000 mg/L). The growth of the eggplant seedlings was suppressed by all the NPs in
      a concentration-dependent manner and among them, NiO was shown to be more toxic
      as it suppressed the root and shoot growth effectively. Total chlorophyll
      contents were decreased in the NP-treated plants compared to control plants.
      Significant changes were found in the secondary metabolites such as anthocyanins,
      total phenolic and total flavonoid contents in the NP-treated plants. A dose
      dependent increase in the reactive oxygen species (ROS) generation was noticed in
      the NP-treated plants which are evidenced by the 4-nitro blue tetrazolium
      chloride (NBT) and 3,3'-diamiobenzidine (DAB) histochemical staining. The DNA
      damage imposed by the NP in the seedlings of eggplants may be due to the elevated
      ROS and MDA (malondialdehyde) production. NiO NP was found to be more toxic
      comparable to CuO and ZnO NPs in the present study. Apart from the toxic effects,
      nanoparticles also showed profound effects on the production of important
      secondary metabolites such as phenolics and flavonoid compounds.

PMID- 30105190
TI  - Expression profile of phenylpropanoid pathway genes in Decalepis hamiltonii
      tuberous roots during flavour development.
AB  - To explore the transcriptional control of phenylpropanoid pathway (PPP) involved
      in vanillin flavour metabolites production in tuberous roots of Decalepis
      hamiltonii, four PPP key genes expressed during the tuber development were
      identified and their mRNA expression profiles were evaluated using quantitative
      real-time PCR. Flavour metabolite quantification by HPLC analysis confirmed 10,
      170 and 500 ug/g 2-hydroxy-4-methoxy benzaldehyde and 4, 20 and 40 ug/g vanillin
      in first- (3-month-old plant), second- (18-month-old plant) and third-stage
      tubers (60-month-old matured plant), respectively. The expression of all four
      genes phenylalanine ammonia lyase (DhPAL), cinnamate-4-hydroxylase (DhC4H),
      caffeic acid-O-methyltransferase (DhCOMT) and vanillin synthase (DhVAN) increased
      with flavour development from first stage to second stage. A decrease in
      expression from 1.9-folds to 0.1-folds and 19.2-folds to 5.2-folds for DhCOMT and
      DhVAN was recorded for second stage to third stage, respectively. However, a
      gradual increase in expression of DhPAL (up to 26.4-folds) and a constant
      expression pattern for DhC4H (up to 7.1-folds) was evident from second stage to
      third stage of flavour development. The decrease in the expression levels of
      DhCOMT and DhVAN in third stage shows that the second-stage tubers are more
      transcriptionally active towards flavour biosynthesis.

PMID- 30105189
TI  - Intercepting signalling mechanism to control environmental biofouling.
AB  - Biofouling in environmental systems employs bacterial quorum sensing signals
      (autoinducers) and extracellular polymeric substances to onset the event. The
      present review has highlighted on the fundamental mechanisms behind biofilm
      formation over broad spectrum environmental niches especially membrane biofouling
      in water systems and consequent chances of pathogenic contamination leading to
      global economic loss. It has broadly discussed on bioelectrical signal (via,
      potassium gradient) and molecular signal (via, AHLs) mediated quorum sensing
      which help to propagate biofilm formation. The review has illustrated the
      potential of genomic intervention towards biofouled membrane microbial community
      and has uncovered possible features of biofilm microenvironment like quorum
      quenching bacteria, bioelectrical waves capture, siderophores arrest and surface
      modifications. Based on information, the concept of interception of quorum
      signals (AHLs) and bioelectrical signals (K+) by employing electro-modified
      (negative charges) membrane surface have been hypothesized in the present review
      to favour anti-biofouling.

PMID- 30105191
TI  - Addition of ionophore A23187 increases the efficiency of Cocos nucifera somatic
      embryogenesis.
AB  - The present study reports the effect of treatment of coconut embryogenic
      structure explants (derived from embryogenic callus) with the calcium ionophore
      A23187 (0, 1, 5, 10 uM) to promote somatic embryogenesis under in vitro
      conditions. The results showed no significant increase in the percentage of
      explants forming embryogenic callus, but with 1 uM ionophore there were
      significant increases in the formation of embryogenic structures per callus (2.8
      fold), of somatic embryos per callus (1.5-fold) and also a greater absolute
      number (1.5-fold) of developing plantlets per callus. The ionophore treatment
      also promoted a change of pattern of the expression of the CnSERK gene during
      embryogenic callus formation. It is proposed that if the use of ionophore A23187
      treatment is coupled with an embryogenic callus multiplication process there
      could be a potentially greater increase in the efficiency of the formation of
      somatic embryos and plantlets of coconut.

PMID- 30105192
TI  - Augmentation of pyrethrins content in callus of Chrysanthemum cinerariaefolium
      and establishing its insecticidal activity by molecular docking of NavMS Sodium
      Channel Pore receptor.
AB  - Pyrethrins are effective food-grade bio-pesticides obtained from the flowers of
      Chrysanthemum cinerariaefolium and this crop cannot be cultivated widely in India
      due to its specific agro-climatic requirement. Hence pyrethrins are mostly
      imported from Kenya. Therefore, the present study aims to develop a process for
      augmentation of pyrethrin contents in C. cinerariaefolium callus and establish
      the correlation between early knockdown effects through docking on grain storage
      insect. In vitro seedlings were used as explants to induce callus on MS medium
      with different concentrations of auxins and cytokinins. Pyrethrin extracted from
      the callus was estimated by RP-HPLC. In callus, total pyrethrin was found to be
      17.5 ug/g, which is higher than that found in natural flowers of certain
      Pyrethrum cultivars. The concentrations of cinerin II, pyrethrin II and jasmoline
      II were quite high in callus grown on solid medium. Bio-efficacy of pyrethrum
      extracts of flower and callus on insect Tribolium sp., showed higher repellency
      and early knock-down effect when compared with pure compound pestanal. Further,
      the rapid knockdown effect of all pyrethrins components was established by
      molecular docking studies targeting NavMS Sodium Channel Pore receptor docking
      followed by multiple ligands simultaneous docking, performed to investigate the
      concurrent binding of different combinations of pyrethrin. Among the six
      pyrethrin components, the pyrethrin I and II were found to be a more efficient,
      binding more firmly to the target, exhibiting higher possibilities of
      insecticidal effect by an early knockdown mechanism.

PMID- 30105193
TI  - Degradation of cinnamic acid by a newly isolated bacterium Stenotrophomonas sp.
      TRMK2.
AB  - A bacterium Stenotrophomonas sp. TRMK2 capable of utilizing cinnamic acid was
      isolated from agro-industrial waste by enrichment culture technique. This strain
      completely utilizes 5 mM cinnamic acid within 18 h of incubation. The different
      metabolites formed during the degradation of cinnamic acid were characterized by
      GC-HRMS. The involvement of various enzymes, namely cinnamate reductase, 3
      phenylpropionic acid hydroxylase, p-hydroxybenzoic acid hydroxylase and
      protocatechuate 3,4-dioxygenase in cinnamic acid degradation was demonstrated. A
      catabolic pathway for cinnamic acid in Stenotrophomonas sp. TRMK2 is as follows:
      Cinnamic acid; 3-Phenylpropionic acid; 3-(4-Hydroxyphenyl) propionic acid; 4
      Hydroxy benzoic acid and Protocatechuic acid. Further, this strain is capable of
      utilizing various phenolic compounds.

PMID- 30105194
TI  - Production and characterization of a thermostable antifungal chitinase secreted
      by the filamentous fungus Aspergillus niveus under submerged fermentation.
AB  - The filamentous fungus Aspergillus niveus produced extracellular antifungal
      chitinase when cultured under submerged fermentation (SbmF) using crab shells as
      the carbon source. Maximal chitinase production was achieved at 192 h of
      cultivation using minimal medium containing 1% chitin. The enzyme was purified
      1.97-fold with 40% recovery by ammonium sulfate precipitation and Sephadex G-100
      gel filtration. The molecular mass was estimated to be 44 kDa by both 12% SDS
      PAGE and Sepharose CL-6B gel filtration. Maximal A. niveus chitinase activity was
      obtained at 65  degrees C and pH 5.0. The enzyme was fully stable at 60  degrees
      C for up to 120 min and the enzymatic activity was increased by Mn2+. In the
      presence of reducing and denaturing compounds, the enzyme activity was not
      drastically affected. The chitinase was able to hydrolyze colloidal chitin, azure
      chitin, and 4-nitrophenyl N-acetyl-beta-D glucosaminide; for the latter, the K0.5
      and maximal velocity (Vmax) were 3.51 mM and 9.68 U/mg of protein, respectively.
      The A. niveus chitinase presented antifungal activity against Aspergillus niger
      (MIC = 84 ug/mL), A. fumigatus (MIC = 21 ug/mL), A. flavus (MIC = 24 ug/mL), A.
      phoenicis (MIC = 24 ug/mL), and Paecilomyces variotii (MIC = 21 ug/mL). The
      fungus A. niveus was able to produce a thermostable and denaturation-resistant
      chitinase able to inhibit fungal development, signaling its biotechnological
      potential.

PMID- 30105195
TI  - Fungal biotransformation of synthetic levodopa to stable dopamine in l-ascorbate
      mediated aerobic-thermophilic biochemical process.
AB  - In the present study, fungal biotransformation of synthetic levodopa to stable
      dopamine in an l-ascorbate-mediated thermophilic-aerobic biochemical reaction was
      investigated. A mutant strain of Aspergillus oryzae EMS-6 was used for the
      preparation of mycelial biomass. The mutant was previously developed through EMS
      induced mutagenesis and repressed against l-cysteine HCl. Growth parameters such
      as rate of cultivation (48 h), initial pH (6) and incubation temperature (30 
      degrees C) supported 18.84 g/l biomass with 23 g/l glucose consumption.
      Thermophilic behaviour of culture was observed at 25-40  degrees C. Kinetic
      variables notably u = 0.385 /h and Qs, exhibited consistent growth pattern.
      Biochemical reactions were performed aerobically using mycelial biomass as the
      source of enzyme 'tyrosinase' in a digital hotplate equipped with magnetic
      stirrers. The reaction conditions included 5 mg/ml biomass and 2.5 mg/ml levodopa
      as basal substrate in a thermophilic reaction of 25 min duration acidified with l
      ascorbic acid. TLC and HPLC analysis of reaction mixture confirmed the presence
      of levodopa and dopamine using a CN-9dth (R) column. Activation enthalpy and
      entropy of dopa decarboxylase (DDC) and its thermal inactivation showed an
      improved biotransformation of levodopa to dopamine at the optimal temperature (30
      degrees C) as compared to other temperatures being employed. Overall, 3.68 mg/ml
      dopamine (4.55 mg/ml proteins) synthesis from 2.38 mg/ml levodopa was
      accomplished. The enhancement in metabolic activity of the mutant strain is ~
      2.75-fold improved when compared to the unoptimized reaction conditions, which is
      highly significant (HS) indicating an eco-commercially viable (LSD ~ 0.412)
      bioprocess.

PMID- 30105196
TI  - Chemopreventive and anti-breast cancer activity of compounds isolated from leaves
      of Abrus precatorius L.
AB  - The present study focuses on isolation and evaluation of the anti-cancer activity
      of compounds from the leaves of Abrus precatorius. The bioassay-directed strategy
      was adopted using chromatographic, gas chromatographic-mass spectrum analysis,
      nuclear magnetic resonance and X-ray crystallography techniques for purification
      and characterization of active cytotoxic compounds. Further, MDA-MB-231 breast
      cancer cell lines and 7,12-dimethylbenz (a) anthracene (DMBA) induced virgin
      female Sprague Dawley (SD) rats were used for in vitro and in vivo cytotoxicity
      evaluation. Stigmasterol hemihydrate and 9,12-Octadecadienoic acid (Z,Z)-2
      hydroxy-1-(hydroxymethyl)ethyl ester or (beta-monolinolein) were the two main
      cytotoxic constituents of leaf extract of A. precatorius, with an IC50 value of
      74.2 and 13.2 ug/ml, respectively, in MDA-MB-231 cells. Additionally, the
      treatment with the stigmasterol and beta-monolinolein as a combinatorial drug
      therapy in DMBA-induced female SD rats led to recovery of body weight, decreased
      tumor weight and volume, without any toxic side effects. Immunohistochemical
      examination showed extensive cell death and low proliferation in the treated
      tumor tissues that was confirmed by results from H and E staining, TUNEL assay
      and Ki-67 index as compared to control animal group. The reversion of
      glycoprotein, lysosomal and tumor marker enzyme levels back to near-normal levels
      after treatment with the plant compounds clearly demonstrated the reduction of
      tumor burden in these animals. This is the first report on isolation and
      characterization of the two active cytotoxic components from leaves of A.
      precatorius. Additionally, the profound cytotoxic and tumor-suppressive effect of
      these two compounds as a combinatorial therapy provide an alternative option for
      breast cancer treatment.

PMID- 30105197
TI  - Optimization of the enzymatic hydrolysis of rice protein by different enzymes
      using the response surface methodology.
AB  - The optimization of the enzymatic hydrolysis of rice protein was determined using
      an experimental design tool. The semi-purified protease of Bacillus licheniformis
      LBA 46 and commercial protease Alcalase 2.4 L were used to produce rice
      hydrolysates using pH values ranging from 6 to 10 and enzyme concentrations
      varying from 50 to 150 U/mL. The optimized conditions were validated, and using
      the chosen conditions (pH 10 and 100 U/mL of protease), it was possible to
      confirm that the model was predictive for oxygen radical absorbance capacity
      (ORAC) and ferric reducing antioxidant power (FRAP) responses. The experimental
      values for the ORAC and FRAP responses were 940 and 18.78 TE umol/g for the rice
      protein hydrolysates prepared with LBA protease and 1001.94 and 19.31 TE umol/g
      for the rice protein hydrolysates prepared with Alcalase 2.4 L. After
      optimization of the enzymatic hydrolysis conditions, the antioxidant activity
      values increased when compared to the values for the intact rice protein: 324.97
      TE umol/g (ORAC) and 6.14 TE umol/g (FRAP). It was also observed that the LBA
      protease had an action similar to the commercial protease, showing its potential
      for application in protein hydrolysis.

PMID- 30105198
TI  - A molecular simulation analysis of vitamin D targets interleukin 13 (IL13) as an
      alternative to mometasone in asthma.
AB  - Asthma, a chronic lung disease characterized by obstruction of airway passage is
      characterized by inflammation and hyperresponsiveness with increase in the number
      of eosinophils. Interleukin-13, plays a significant role in causing inflammation
      during an asthmatic attack by bronchial constriction. Mometasone, a
      glucocorticoid has been used as the first line of administration for people
      affected with asthma for almost a decade. However, in several cases, people
      treated with mometasone have faced systemic and local side effects. To reduce
      these side effects, we hypothesized vitamin D that can be used as a substitute to
      mometasone. For this purpose, we employed the use of molecular docking and
      simulation studies for comparative study. The docking studies revealed the
      binding residues of interleukin-13 which are bound to the active site. Among all,
      we noticed three binding residue Leu83, His84 and Arg86 common for both
      mometasone and vitamin D. Also, the binding energies share a significant
      similarity between them. The docked complexes of mometasone and vitamin D with
      interleukin-13 were evaluated with molecular dynamics simulation. Consistently,
      the MD analysis uncovered the interesting note on conformational adaptation
      between the complexes as well as that vitamin D has the complementary binding
      efficiency to interleukin-13 as compared to mometasone. The substitution of
      vitamin D might provide a promising gateway to reduce the side effects caused by
      mometasone and also reduce the cost for treatment of asthma patients.

PMID- 30105199
TI  - Extraction of lignin, structural characterization and bioconversion of sugarcane
      bagasse after ionic liquid assisted pretreatment.
AB  - The primary focus of this work was to recover lignin and investigate the
      structural changes in sugarcane bagasse after pretreatment with ionic liquid 1
      ethyl-3-methylimidazolium acetate ([EMIM]oAc). 90% lignin recovery was achieved
      while bagasse was treated with [EMIM]oAc at 140  degrees C, 120 min reaction time
      and 1:20 bagasse to the ionic liquid ratio (w/w). The impact of ionic liquid
      pretreatment on bagasse was confirmed by qualitative analysis of untreated and
      pretreated bagasse. Scanning electron microscopy analysis exhibited the porous
      and irregular structure of bagasse after pretreatment. X-ray powder diffraction
      analysis verified a decrease in crystallinity as a result of the pretreatment
      process by showing a 14.7% reduction of Crystallinity index after ionic liquid
      treatment. The efficacy of [EMIM]oAc on bagasse treatment was also examined by
      enzymatic hydrolysis which manifested an increase in reducing sugar yield as a
      result of pretreatment. Maximum yield of 54.3% reducing sugar was obtained after
      72 h enzymatic hydrolysis of pretreated bagasse. Recovered lignin was analyzed
      qualitatively. 1D NMR spectroscopy of lignin revealed the presence of essential
      functional groups whereas 2D NMR spectroscopy showed the dominance of etherified
      syringyl unit. Further ionic liquid recovery and reuse were substantiated by Gel
      permeation chromatography analysis of lignin. Weight average molecular weight
      (Mw) of lignin extracted by fresh [EMIM]oAc was obtained as 1769 g/mol (in the
      previous study) while lignin recovered by recycled [EMIM]oAc showed almost equal
      Mw 1765 g/mol in this study. Thus, the current investigation corroborated
      satisfactory performance of [EMIM]oAc in lignocellulose processing which further
      enhanced enzymatic hydrolysis in the subsequent step.

PMID- 30105200
TI  - One-step electrochemically synthesized graphene oxide coated on polypyrrole
      nanowires as anode for microbial fuel cell.
AB  - A novel polypyrrole nanowires coated by graphene oxide (PPy-NWs/GO) has been
      successfully synthesized by one-step electrochemical method, whose structure was
      different from previously reported PPy/GO composites. The microbial fuel cell
      equipped with PPy-NWs/GO as anode was fabricated and compared with PPy-NWs ones.
      The SEM images show that the synthesized PPy-NWs/GO materials possess more
      surface areas than PPy-NWs. The electrochemical analysis indicated that PPy
      NWs/GO anode had lower charge transfer resistance, which may be attributed to
      synergistic effect of them. The MFC equipped with PPy-NWs/GO anode have higher
      circle voltages and the power density is about 22.3 mW/m2, which is great higher
      than that of PPy-NWs about 15.9 mW/m2. These improvements of the MFCs may be due
      to more bacteria on the larger biofilms based on GO nanosheets, indicating that
      the PPy-NWs/GO is more effective anode for improving electricity generation.

PMID- 30105201
TI  - Complete genome sequence of Rhodothermaceae bacterium RA with cellulolytic and
      xylanolytic activities.
AB  - Rhodothermaceae bacterium RA is a halo-thermophile isolated from a saline hot
      spring. Previously, the genome of this bacterium was sequenced using a HiSeq 2500
      platform culminating in 91 contigs. In this report, we report on the resequencing
      of its complete genome using a PacBio RSII platform. The genome has a GC content
      of 68.3%, is 4,653,222 bp in size, and encodes 3711 genes. We are interested in
      understanding the carbohydrate metabolic pathway, in particular the
      lignocellulosic biomass degradation pathway. Strain RA harbors 57 glycosyl
      hydrolase (GH) genes that are affiliated with 30 families. The bacterium consists
      of cellulose-acting (GH 3, 5, 9, and 44) and hemicellulose-acting enzymes (GH 3,
      10, and 43). A crude cell-free extract of the bacterium exhibited endoglucanase,
      xylanase, beta-glucosidase, and beta-xylosidase activities. The complete genome
      information coupled with biochemical assays confirms that strain RA is able to
      degrade cellulose and xylan. Therefore, strain RA is another excellent member of
      family Rhodothermaceae as a repository of novel and thermostable cellulolytic and
      hemicellulolytic enzymes.

PMID- 30105202
TI  - A chest tube translocating the posterior mediastinum: A strange case of
      malpositioning without complication or injury.
AB  - Malpositioning of a chest tube is a recognised complication of chest tube
      insertion. However, cases involving the mediastinum comprise only a fraction of
      such occurrences, while the complete translocation of the tube through the
      medisastinum is only noted in three published cases. This case report describes a
      case of complete translocation of the mediastinum during chest tube insertion to
      resolve a pneumothorax. It examines the possibility of an occult natural pathway
      in the posterior mediastinum of some patients based on the ease at which the tube
      crossed the mediastinum, the immediate resolution of patient symptoms and the
      absence of injury or complications from the event to the patient.

PMID- 30105206
TI  - Pasteurella multocida prosthetic joint infection.

PMID- 30105204
TI  - Applying dynamic contrast enhanced MSOT imaging to intratumoral pharmacokinetic
      modeling.
AB  - Examining the dynamics of an agent in the tumor microenvironment can offer
      critical insights to the influx rate and accumulation of the agent. Intratumoral
      kinetic characterization in the in vivo setting can further elicudate
      distribution patterns and tumor microenvironment. Dynamic contrast-enhanced
      Multispectral Optoacoustic Tomographic imaging (DCE-MSOT) acquires serial MSOT
      images with the administration of an exogenous contrast agent over time. We
      tracked the dynamics of a tumor-targeted contrast agent, HypoxiSense 680 (HS680),
      in breast xenograft mouse models using MSOT. Arterial input function (AIF)
      approach with MSOT imaging allowed for tracking HS680 dynamics within the mouse.
      The optoacoustic signal for HS680 was quantified using the ROI function in the
      ViewMSOT software. A two-compartment pharmacokinetics (PK) model constructed in
      MATLAB to fit rate parameters. The contrast influx (kin) and outflux (kout) rate
      constants predicted are kin = 1.96 * 10-2 s-1 and kout = 9.5 * 10-3 s-1 (R =
      0.9945).

PMID- 30105205
TI  - Photoacoustic imaging of integrin-overexpressing tumors using a novel ICG-based
      contrast agent in mice.
AB  - PhotoAcoustic Imaging (PAI) is a biomedical imaging modality currently under
      evaluation in preclinical and clinical settings. In this work, ICG is coupled to
      an integrin binding vector (ICG-RGD) to combine the good photoacoustic properties
      of ICG and the favourable alphavbeta3-binding capabilities of a small RGD cyclic
      peptidomimetic. ICG-RGD is characterized in terms of physicochemical properties,
      biodistribution and imaging performance. Tumor uptake was assessed in
      subcutaneous xenograft mouse models of human glioblastoma (U-87MG, high
      alphavbeta3 expression) and epidermoid carcinoma (A431, low alphavbeta3
      expression). ICG and ICG-RGD showed high PA signal in tumors already after 15 min
      post-injection. At later time points the signal of ICG rapidly decreased, while
      ICG-RGD showed sustained uptake in U-87MG but not in A431 tumors, likely due to
      the integrin-mediated retention of the probe. In conclusion, ICG-RGD is a novel
      targeted contrast agents for PAI with superior biodistribution, tumor uptake
      properties and diagnostic value compared to ICG.

PMID- 30105207
TI  - Chronic prostatitis developing due to candida infection: A case diagnosed 20
      years later and review of up-to-date literature.

PMID- 30105208
TI  - About a case of ureteropelvic junction obstruction in L-shaped cross-fused
      kidney.

PMID- 30105203
TI  - Increased efficiency of brain connectivity networks in veterans with suicide
      attempts.
AB  - Background: Suicide is a public health concern for United States veterans and
      civilians. Prior research has shown neurobiological factors in suicide. However,
      studies of neuroimaging correlates of suicide risk have been limited. This study
      applied complex weighted network analyses to characterize the neural connectivity
      in white matter in veterans with suicide behavior. Methods: Twenty-eight veterans
      without suicide behavior (NS), 29 with a history of suicidal ideation only (SI),
      and 23 with prior suicide attempt (SA) completed diffusion tensor brain imaging,
      the Columbia Suicide Severity Rating Scale and Barratt Impulsiveness Scale (BIS).
      Structural connectivity networks among 82 parcellated brain regions were produced
      using whole-brain tractography. Global and nodal metrics of network topology have
      been calculated. Results: SA had shorter characteristic path length and greater
      global efficiency and mean weighted degree of global network metrics (p < 0.024).
      SA had more hub nodes than NS and SI. The left posterior cingulate cortex (PCC)
      showed significantly greater weighted degree in SA relative to others (p <
      0.0003). Nonplanning subscale of BIS correlated with the weighted degrees of the
      left PCC within SA. In rich club connectivity, SA had higher local connections
      than others (p = 0.001). Conclusion: Veterans with prior suicide attempt had
      altered connectivity networks characteristics in the white matter. These findings
      may be distinctive neurobiological markers for individuals with suicide attempt.
      Strong connectivity in the left PCC may be implicated in impulsivity in veterans
      with suicide attempt.

PMID- 30105209
TI  - Microcystins in water and in microalgae: Do microcystins as microalgae
      contaminants warrant the current public alarm?
AB  - Microcystins have been the subject of increasingly alarming popular and
      scientific articles, which have taken as their unquestionable foundation the
      provisional Guideline of 1 MUg/L established by the WHO Panel on microcystins
      levels in water, and mechanically translated by the Oregon government as 1 MUg/g
      of Klamath Aphanizomenon flos aquae microalgae. This article underlines the
      significant limitations and ultimately scientific untenability of the WHO
      Guideline on microcystins in water, for being based on testing methodologies
      which may lead to a significant overestimation of the toxicity of microcystins. I
      propose criteria for the realization of new experimental studies on the toxicity
      of microcystins, based on the essential understanding that drinking water is
      contaminated by whole cyanobacterial microalgae rather than purified
      microcystins, while it is important to differentiate between water and
      cyanobacterial supplements. It is indeed a mistake to automatically apply
      standards that are proper for water to cyanobacterial supplements, as they have
      different concentrations of the antioxidant substances that inactivate or
      significantly reduce the toxicity of microcystins, a fact that also require that
      each cyanobacterial supplement be tested individually and through realistic
      testing methodologies.

PMID- 30105210
TI  - Performance of a whole-body human dust inhalation challenge exposure chamber.
AB  - Background: Evaluation of the performance of a whole-body human dust exposure
      chamber is presented in this report. Methods: The volume of the chamber is 2.13
      m3 and it is operated at a flow rate of 1.0 m3/min. Makeup and exhaust air were
      filtered. A Wright Dust Feeder was used to generate fly ash, the testing agent.
      An elutriator was used to maintain particles in the respirable range. A Rupprecht
      and Patashnick PM-10 TEOM, a direct reading instrument, was used to monitor
      particle concentration. Particle size distributions were determined by a QCM
      cascade impactor. The evenness of dust concentrations in the chamber was
      determined gravimetrically. Results: Dust concentrations measured at different
      points within the chamber were associated with variability less than 10%. Dust
      concentrations measured by the TEOM, in MUg/m3, at 0.2, 0.4, 0.8 and 1.6 RPMs of
      the Wright Dust Feeder, were 110 +/- 2.8, 173 +/- 8.5, 398 +/- 20 and 550 +/- 17,
      respectively. Particle size distributions (MMD and GSD) were 1.27 MUm and 2.35,
      1.39 and 2.22, 1.46 and 2.08, 1.15 and 2.2, respectively. Total dust
      concentrations measured gravimetrically in MUg/m3, were 135 +/- 21, 200 +/- 35,
      333 +/- 18 and 891 +/- 27, respectively. Conclusion: The whole-body human
      exposure chamber offers several advantages and has better performance than most
      of the inhalation challenge systems previously described.

PMID- 30105211
TI  - Positive symptoms and time perception in schizophrenia: A meta-analysis.
AB  - Positive symptoms of schizophrenia may be related to distortions in time
      perception. To examine this issue, we conducted a meta-analysis to determine
      whether positive symptoms are associated with deficits in time processing
      performance. MEDLINE and Web of Science were searched from January 1980 through
      March 2017, and all related articles and their references were scrutinized to
      find relevant studies. Studies were selected if they included participants with a
      diagnosis of schizophrenia, and reported data from behavioral measures of
      interval timing (e.g. duration discrimination and temporal order judgement). The
      results indicated that positive symptoms of schizophrenia are related with
      overestimation of interval timing (i.e., acceleration of the "internal clock"),
      and suggest that time perception may be associated with psychosis.

PMID- 30105212
TI  - Superior memory performance in healthy individuals with subclinical psychotic
      symptoms but without genetic load for schizophrenia.

PMID- 30105213
TI  - Long-term trend of and correlation between vegetation greenness and climate
      variables in Asia based on satellite data.
AB  - Satellite data has been used to ascertain trends and correlations between climate
      change and vegetation greenness in Asia. Our study utilized 33-year (1982-2014)
      AVHRR-GIMMS (Advanced Very High Resolution Radiometer-Global Inventory Modelling
      and Mapping Studies) NDVI3g and CRU TS (Climatic Research Unit Time Series)
      climate variable (temperature, rainfall, and potential evapotranspiration) time
      series. First, we estimated the overall trends for vegetation greenness and
      climate variables and analyzed trends during summer (April-October), winter
      (November-March), and the entire year. Second, we carried out correlation and
      regression analyses to detect correlations between vegetation greenness and
      climate variables. Our study revealed an increasing trend (0.05-0.28) in
      temperature in northeastern India (bordering Bhutan), Southeast Bhutan, Yunnan
      Province of China, Northern Myanmar, Central Cambodia, northern Laos, southern
      Vietnam, eastern Iran, southern Afghanistan, and southern Pakistan. However, a
      decreasing trend in temperature (0.00 to -0.04) was noted for specific areas in
      southern Asia including Central Myanmar and northwestern Thailand and the
      Guangxi, Southern Gansu, and Shandong provinces of China. The results also
      indicated an increasing trend for evapotranspiration and air temperature
      accompanied by a decreasing trend for vegetation greenness and rainfall.
      Increases in both the mean annual signal and annual cycle occurred in the forest,
      herbaceous, and cropland areas of India, Northwest China, and eastern Kazakhstan.
      The temperature was found to be the main driver of the changing vegetation
      greenness in Kazakhstan, northern Mongolia, Northeast and Central China, North
      Korea, South Korea, and northern Japan, showing an indirect relationship (R =
      0.84-0.96). *Temperature is the main climatic variable affecting vegetation
      greenness.*A downward trend in vegetation greenness was observed during summer
      (April-October).*Temperature showed an upward trend across many areas of Asia
      during the study period.*In winter, rainfall showed downward and upward trends in
      different parts of Asia.

PMID- 30105214
TI  - Replicating carbonaceous vug in synthetic porous media.
AB  - This paper presents an alternative method of creating vuggy glass-bead core
      proxies, which can be used to investigate the effects of pore-scale features on
      carbonate petrophysical properties. Carbonates are complex rocks having a
      widespread variation in pore type, size, distribution, and porosity. With this
      method we can control vug shape, size, and position. Homogeneous glass bead core
      proxies are sintered using 1.0 mm diameter glass beads in a muffle furnace. Vugs
      are 3D-printed in plastic and used to make a mold in Play-Doh(r); which is cast
      in gypsum cement and used as a placeholder during the sintering process. The
      gypsum vug dissolves during acid flood, leaving an empty space inside the glass
      matrix. Computed tomography (CT) scans are made of the acid washed vug space and
      compared to the 3D model.

PMID- 30105215
TI  - Comparative histopathology and immunohistochemistry of human and canine mammary
      tumors.
AB  - This study aimed at establishing aspects of comparison between canine and human
      mammary gland tumors. In order to achieve that, 44 specimens of canine mammary
      tumors and 70 specimens of human breast tumors were examined in order to state
      points of similarity in morphology, cells of origin, behavior and existence of
      tissue markers. We found that the ratio of benign to malignant forms was 4.5% to
      95.5% in canine samples and 45.7% to 54.3% in human samples. In both species,
      malignant tumors composed of infiltrating ductal cells were in the forefront
      despite dissimilarity in nomenclature. Other kinds of lower rate of existence
      included, invasive micro-papillary carcinoma, mucinous carcinoma and invasive
      comedo-carcinoma which have displayed similar morphology and terminology in both
      species. Chondroid and squamous differentiation were found in human and canine
      specimens. In human samples, fibro-adenoma mounted up to 30 out of 32 benign
      tumors (93.8%). Her-2 and Ki-67 were detected in the specimens of both species
      but ER was detected in human specimens only. Our findings suggest a significant
      degree of resemblance between certain mammary tumor in canine and human. Such
      findings are in support of employing dogs in research investigation for human
      mammary tumors.

PMID- 30105216
TI  - Sertoli cell tumour in a pet rabbit (Oryctolagus cuniculus): histological and
      immunohistochemical characterization.
AB  - The present study describes a case of a spontaneous, unilateral Sertoli cell
      tumour (SCT) in a 6-year-old pet rabbit. The rabbit was presented with a
      palpable, unilateral, subcutaneous left inguinal mass, consistent with the
      suspected clinical diagnosis of neoplasia developing within the retained testis
      in the inguinal canal. The intrascrotal contralateral testis was palpable, but
      reduced in volume. The rabbit underwent orchiectomy and both the testes were
      collected, formalin-fixed, and submitted for histopathological examination.
      Microscopically, the enlarged testis was effaced by an intratubular SCT in which
      numerous intratubular microliths were evident. The contralateral testis was
      severely atrophied. Immunohistochemical stains showed neoplastic Sertoli cells
      that were diffusely positive for vimentin and anti-Mullerian-Hormone and
      multifocally positive for cytokeratins and desmin. Eighteen months after the
      surgery, the rabbit showed no clinical signs of disease. This is the first report
      of a spontaneously occurring rabbit SCT histologically described and
      immunohistochemically investigated.

PMID- 30105217
TI  - Organ-Specific Toxicities Due to Radiation Therapy in Cancer Patients With or
      Without HIV Infection: A Systematic Review of the Literature.
AB  - Background: To synthesize published literature on the association between human
      immunodeficiency virus (HIV) infection and radiation therapy (RT)-related
      toxicities. Methods: Two electronic databases, MEDLINE and Embase, were searched
      to identify studies published before November 2016 comparing RT-related
      toxicities between HIV-infected and HIV-uninfected patients receiving RT or
      chemoradiation therapy (CRT) for cancer. A qualitative synthesis of included
      articles and organ-specific toxicities was then performed. Results: Of the 21
      studies included in this review, 15 reported on anal cancer treatment, three on
      cervical cancer, two on Kaposi sarcoma, and one on prostate cancer. Reports in
      the pre-antiretroviral therapy (ART) or early ART era tended to identify
      increased morbidity and mortality with HIV infection. However, modern series
      incorporating more concurrent chemotherapy, conformal RT techniques, and ART
      administration result in fewer studies reporting toxicity differences in patients
      treated for anal and cervical cancers. When statistically significant, HIV
      infected patients had higher rates of gastrointestinal toxicity with anal cancer
      CRT (up to 50%) and higher rates of hematologic toxicity with cervical cancer CRT
      (up to 31%). Of the 17 studies reporting treatment outcomes, nine suggest HIV
      infected patients may have reduced local control and/or survival rates.
      Conclusions: Overall, RT is likely similarly tolerated between HIV-infected and
      HIV-uninfected patients, especially with modern RT techniques. HIV-infected
      patients should continue to receive established standard of care RT and CRT
      dosing.

PMID- 30105218
TI  - Review of checkpoint immunotherapy for the management of non-small cell lung
      cancer.
AB  - Checkpoint immunotherapy uses highly selective humanized monoclonal antibodies
      against checkpoint signals such as programmed cell death receptor (PD-1) and
      programmed cell death ligand (PD-L1). By blocking these receptors and signals,
      the immune system can be reactivated to fight the tumor. Immunotherapy for
      advanced non-small cell lung cancer (NSCLC) has resulted in a new paradigm of
      treatment options resulting in improved survival and response rates and has a
      less severe yet unique toxicity profile when compared to chemotherapy. PD-1
      inhibitors, nivolumab and pembrolizumab, and PD-L1 inhibitor, atezolizumab, are
      currently approved by regulatory authorities for the treatment of advanced NSCLC.
      This article provides a detailed review of these newer agents, their mechanism of
      action, side-effect profile, therapeutic indications and current evidence
      supporting their use in the management of NSCLC.

PMID- 30105220
TI  - Diode laser surgery in the treatment of oral proliferative verrucous leukoplakia
      associated with HPV-16 infection.
AB  - Background: Proliferative verrucous leukoplakia (PVL) is an oral potentially
      malignant disorder, characterized by multifocal expression, progressive clinical
      evolution, and a high rate of malignant transformation. Evidence-based
      information regarding optimal PVL management is lacking, due to the paucity of
      data. The present report describes a case of PVL associated with HPV-16 infection
      and epithelial dysplasia treated by diode laser surgery, and the outcome of
      disease clinical remission over a 2-year follow-up period. Case report: A 61-year
      old Caucasian male with oral verrucous hyperkeratosis presented for diagnosis.
      The lesions were localized on the maxillary gingiva and palatal alveolar ridge.
      Multiple biopsy specimens have been taken by mapping the keratotic lesion area.
      Microscopic examination was compatible with a diagnosis of PVL with focal mild
      dysplasia, localized in the right maxillary gingiva. Polymerase chain reaction
      (PCR) was done for human papillomavirus (HPV) detection which revealed presence
      of HPV DNA, and the genotype revealed HPV 16 in the sample. The PVL in the right
      gingival area was treated on an outpatient basis by excision with a diode laser.
      This approach resulted in good clinical response and decreased morbidity over a 2
      year follow-up period. Conclusions: This case illustrates the benefit of a
      conservative approach by diode laser treatment than wide surgical excision for
      management of the PVL lesions associated with mild dysplasia and HPV-16
      infection.

PMID- 30105221
TI  - Postoperative long-term results for the comparison of the symmetry of the upper
      lip during lip closure according to Millard and Pfeifer.
AB  - Background: Clefts in newborns are associated with severe morphological and
      functional impairment. Especially the lip is of importance as if the treatment
      result is unsatisfactory, it can lead to psychological changes in the patient.
      Different operative procedures have been developed over the last decades. The aim
      of the presented study was the comparison of the surgical techniques according to
      Millard and Pfeifer regarding the temporal development of the postoperative
      symmetry of the lip height and mouth width. Methods: Digitized photographs of
      patients from the department of oral and maxillofacial surgery at the University
      of Gottingen were evaluated from 1979 to 1996. With a video analysis program, the
      lip height and mouth width were analyzed regarding the symmetry. We demonstrated
      the symmetry values over a period of 8 years in order to show the influence of
      growth on postoperative results. Results: The development of the vertical
      symmetry of the Philtrum and the lip vermillion on the cleft side in comparison
      to the healthy side behaves differently depending on Pfeifer and Millard. The lip
      height of the cleft lip was shorter in both techniques than on the healthy side,
      but Pfeifer's difference was significantly more pronounced. The lip vermillion
      height on the cleft side was slightly shorter in the Millard group and markedly
      larger in the Pfeifer group. Both techniques can achieve good symmetry results
      for the vertical dimension of the lip. According to Pfeifer, the development of
      the horizontal dimension on the cleft side is bigger within the first 4 years
      than on the healthy side; according to the Millard technique, the horizontal
      development is smaller. These differences are greater within the first 6 years
      and approach between the 6th and 8th year. Conclusions: The Millard technique
      demonstrates better results concerning the philtrum and vermillion symmetry
      during growth within the first 6 years. Over the whole study period, growth
      corrects the philtrum and vermillion symmetry within the Pfeifer group.

PMID- 30105222
TI  - Editorial: Extra-Corporeal Membrane Oxygenation in Pediatric Cardiac Patients.

PMID- 30105219
TI  - Oncolytic virus and PD-1/PD-L1 blockade combination therapy.
AB  - Oncolytic viruses are lytic for many types of cancers but are attenuated or
      replication-defective in normal tissues. Aside from tumor lysis, oncolytic
      viruses can induce host immune responses against cancer cells and may thus be
      viewed as a form of immunotherapy. Although recent successes with checkpoint
      inhibitors have shown that enhancing antitumor immunity can be effective, the
      dynamic nature of the immunosuppressive tumor microenvironment presents
      significant hurdles to the broader application of these therapies. Targeting one
      immune-suppressive pathway may not be sufficient to eliminate tumors. Here we
      focus on the development of the combination of oncolytic virotherapy with
      checkpoint inhibitors designed to target the programmed cell death protein 1 and
      programmed cell death ligand 1 signaling axis. We also discuss future directions
      for the clinical application of this novel combination therapy.

PMID- 30105223
TI  - Efficient Calculation of the Negative Thermal Expansion in ZrW2O8.
AB  - We present a study of the origin of the negative thermal expansion (NTE) on
      ZrW2O8 by combining an efficient approach for computing the dynamical matrix with
      the Lanczos algorithm for generating the phonon density of states in the quasi
      harmonic approximation. The simulations show that the NTE arises primarily from
      the motion of the O-sublattice, and in particular, from the transverse motion of
      the O atoms in the W-O and W-O-Zr bonds. In the low frequency range these combine
      to keep the WO4 tetrahedra rigid and induce internal distortions in the ZrO6
      octahedra. The force constants associated with these distortions become stronger
      with expansion, resulting in negative Gruneisen parameters and NTE from the low
      frequency modes that dominate the positive contributions from the high frequency
      modes. This leads us to propose an anharmonic, two-frequency Einstein model that
      quantitatively captures the NTE behavior.

PMID- 30105224
TI  - Investigation of Atrazine Sorption to Biochar With Titration Calorimetry and Flow
      Through Analysis: Implications for Design of Pollution-Control Structures.
AB  - Atrazine is one of the most common broad-leaf herbicides used in the world.
      However, due to extensive use for many years, atrazine often appears in surface
      and groundwater. Atrazine transport is inhibited by degradation or sorption to
      soil components, especially organic matter. Biochar is a charcoal-like material
      produced from pyrolysis of biomass. Due to the amount and type of functional
      groups found on biochar, this product has shown potential for sorption of
      atrazine from solution. There is an interest in developing best management
      practices utilizing biochar to filter atrazine from non-point drainage with
      pollution-control structures such as blind inlets. The objective of this study
      was to explore the kinetics and thermodynamics of atrazine sorption to biochar
      using two different approaches: flow-through sorption cells and isothermal
      titration calorimetry (ITC). Twenty-five milligrams of an oak (Quercus spp.)
      derived biochar was suspended in water and titrated 25 times (0.01 mL per
      titration) with atrazine at three different concentrations, and by a single
      titration (0.25 mL), with heat of reaction directly measured with ITC. A benchtop
      atrazine sorption study that simulated the titration experiment was also
      conducted. A continuous flow-through system was used to quantify the impact of
      contact time on atrazine sorption to biochar. Atrazine sorption to biochar
      displayed both exothermic and endothermic signals within each titration, although
      the net reaction was exothermic and proportional to the degree of sorption. Net
      enthalpy was -4,231 +/- 130 kJ mole-1 atrazine sorbed. The existence of both
      exotherms and endotherms within a single titration, plus observation of an
      initial fast reaction phase from 0 to 300 s followed by a slower phase, suggested
      multiple sorption mechanisms to biochar. Results of flow-through tests supported
      kinetics observations, with the 300 s contact time removing much more atrazine
      compared to 45 s, while 600 s improved little compared to 300 s. Based on flow
      through results, annual atrazine removal goal of 50%, and typical Midwestern U.S.
      tile drainage conditions, a pollution-control structure implementing this biochar
      sample would require 32 and 4 Mg for a design utilizing a contact time of 45 and
      300 s, respectively. Future work is necessary for estimating degradation of
      atrazine sorbed to biochar.

PMID- 30105225
TI  - Facile Preparation of Hydrophobic Aluminum Oxide Film via Sol-Gel Method.
AB  - Hydrophobic aluminum oxide films (AOFs) are widely used in anti-oxidation and
      anti-corrosion applications. In preparing AOFs, complex and high temperature
      conditions are usually necessary. Here, we report aluminum nanowire structures
      with hydrophobic properties, prepared using a facile sol-gel method by magnetic
      stirrer and hydrothermal reaction. The electromagnetic force work has great
      influence on the structure of AOFs. The surface morphology and compositions of
      the AOFs were analyzed by scanning electron microscope (SEM), energy dispersive X
      ray spec-trometers (EDS), X-ray diffraction (XRD), 3M peeling test, and X-ray
      photoelectron spectroscopy (XPS). With the increase of water content in
      hydrothermal reaction, the hydrophobicity of AOFs proportional increased. Adding
      10 ml deionized water leads to the formation of the upper nanowires and the lower
      nanohole with 129.3 degrees  water contact angle. Meanwhile, the AOF provide a
      good substrate for electroless deposition (ELD) of copper (Cu) to achieve a
      simple fabrication of metal conductor.

PMID- 30105227
TI  - Are Endovascular Interventions for Central Vein Obstructions due to Cardiac
      Implanted Electronic Devices Effective?
AB  - Objective: One of the late-onset complications of cardiac implanted electronic
      devices (CIEDs) is central venous obstruction (CVO). The aim of this study was to
      investigate the feasibility, efficacy, and safety of endovascular treatment of
      CIED-related CVOs. Methods:Eighteen patients who underwent endovascular
      management of their device-related CVO were reviewed. Patients were classified
      into three groups: Group I patients were asymptomatic and needed lead
      replacement; Group II patients presented with symptomatic CVO without lead
      dysfunction, and Group III patients were referred with both symptomatic CVO and
      lead dysfunction. A treatment strategy involved recanalization and balloon
      angioplasty for Group I and angioplasty/stents for Groups II and III. Technical
      success, clinical success, complications, and long-term follow-up were assessed.
      Results: Thirteen patients were in Group I, four in Group II, and one in Group
      III. Technical and clinical success was achieved in 17 patients (94%). No major
      complications were reported. Restenosis was observed in two patients at 40 and 42
      weeks of follow-up, and these patients were successfully treated with
      angioplasty. Conclusion: Endovascular management of CVO due to CIED is a safe and
      efficient technique. Plain balloon angioplasty is sufficient for lead replacement
      purposes, while stenting is needed for symptomatic CVO to achieve good long-term
      patency.

PMID- 30105228
TI  - Illumina Next Generation Sequencing for the Analysis of Eimeria Populations in
      Commercial Broilers and Indigenous Chickens.
AB  - Eimeria species parasites can cause the enteric disease coccidiosis, most notably
      in chickens where the economic and welfare implications are significant. Seven
      Eimeria species are recognized to infect chickens, although understanding of
      their regional occurrence, abundance, and population structure remains limited.
      Reports of Eimeria circulating in chickens across much of the southern hemisphere
      with cryptic genotypes and the capacity to escape current anticoccidial vaccines
      have revealed unexpected levels of complexity. Consequently, it is important to
      supplement validated species-specific molecular diagnostics with new genus-level
      tools. Here, we report the application of Illumina MiSeq deep sequencing to
      partial 18S rDNA amplicons generated using Eimeria genus-specific primers from
      chicken caecal contents collected in India. Commercial Cobb400 broiler and
      indigenous Kadaknath type chickens were sampled under field conditions after co
      rearing (mixed type farms, n = 150 chickens for each) or separate rearing (single
      type farms, n = 150 each). Comparison of MiSeq results with established Internal
      Transcribed Spacer (ITS) and Sequence Characterised Amplified Region (SCAR)
      quantitative PCR assays suggest greater sensitivity for the MiSeq approach. The
      caecal-dwelling Eimeria tenella and E. necatrix dominated each sample set,
      although all seven species which infect chickens were detected. Two of the three
      cryptic Eimeria genotypes were detected including OTU-X and OTU-Y, the most
      northern report for the latter to date. Low levels of DNA representing other
      Eimeria species were detected, possibly representing farm-level contamination
      with non-replicating oocysts or Eimeria DNA, or false positives, indicating a
      requirement for additional validation. Next generation deep amplicon sequencing
      offers a valuable resource for future Eimeria studies.

PMID- 30105231
TI  - Turning point for cancer management.

PMID- 30105230
TI  - Concentrations of Plasma Nucleosomes but Not Cell-Free DNA Are Prognostic in Dogs
      Following Trauma.
AB  - Trauma is common in dogs and causes significant morbidity and mortality, but it
      remains a challenge to assess prognosis in these patients. This study aimed to
      investigate the use of plasma cell-free DNA (cfDNA) and nucleosome concentrations
      as prognostic biomarkers in canine trauma. Using a prospective, observational
      case-control study design, 49 dogs with trauma were consecutively enrolled from
      07/2015 to 10/2017 and followed to hospital discharge. Dogs with animal trauma
      triage (ATT) scores >=3 at presentation were eligible for enrollment. Dogs <3 kg
      or with pre-existing coagulopathies were excluded. Thirty-three healthy control
      dogs were also enrolled. Illness and injury severity scores were calculated using
      at-presentation data. Plasma cfDNA was measured in triplicate using a benchtop
      fluorimeter. Plasma nucleosome concentrations were determined in duplicate by
      ELISA. Mann-Whitney U tests were used to compare biomarker concentrations between
      groups and between survivors and non-survivors. Associations between biomarkers
      were evaluated using Spearman's correlation coefficients. Alpha was set at 0.05.
      Concentrations of cfDNA and nucleosomes were significantly higher in injured dogs
      compared to healthy controls (P <= 0.0001). Nucleosomes and cfDNA concentrations
      were positively correlated (rs 0.475, P < 0.001). Concentrations of both cfDNA
      and nucleosomes were correlated with shock index (rs 0.367, P = 0.010, rs 0.358,
      P = 0.012 respectively), but only nucleosomes were correlated with ATT (rs 0.327,
      P = 0.022) and acute patient physiology and laboratory evaluation (APPLE) scores
      (rs 0.356, P = 0.012). Median nucleosome concentrations were significantly higher
      in non-survivors than in survivors [8.2 AU (3.1-26.4) vs. 1.6 AU (0.5-5.2); P =
      0.01]. Among illness severity scores, only APPLE was discriminant for survival
      (AUROC 0.912, P < 0.001). In summary, in moderately-severely injured dogs, high
      nucleosome concentrations are significantly associated with non-survival.

PMID- 30105229
TI  - High Mobility Group Box-1 and Pro-inflammatory Cytokines Are Increased in Dogs
      After Trauma but Do Not Predict Survival.
AB  - Trauma is common in dogs and causes significant morbidity and mortality, but it
      remains challenging to predict the prognosis of dogs with traumatic injuries.
      This study aimed to quantify plasma high-mobility group box-1 (HMGB-1) and
      cytokine concentrations in dogs with moderate-to-severe trauma, and to evaluate
      the association between these biomarkers and the injury severity and survival to
      discharge. Using a prospective, observational case-control study design, 49 dogs
      with an animal trauma triage (ATT) score >=3 were consecutively enrolled from
      07/2015 to 10/2017 and followed to hospital discharge. Dogs <3 kg and those with
      pre-existing coagulopathies were excluded. Thirty three healthy control dogs were
      also enrolled. Illness and injury severity scores including the acute patient
      physiologic and laboratory evaluation (APPLE) were calculated using at
      presentation data. Plasma HMGB-1 concentrations were measured by ELISA;
      concentrations of 13 cytokines were measured using multiplex bead-based assays
      and separately concentrations of 4 cytokines were measured using a multiplex
      canine-specific ELISA. All biomarkers were measured in duplicate. Mann-Whitney U
      tests were used to compare biomarker concentrations between groups and between
      survivors and non-survivors. Associations between biomarkers were evaluated using
      Spearman's correlation coefficients. Independent predictors of survival were
      identified using multivariable logistic regression. Alpha was set at 0.05. Plasma
      concentrations of HMGB-1, interleukin-6, C-X-C motif chemokine-8, keratinocyte
      chemoattractant-like, and C-C chemokine ligand-2 were significantly greater in
      injured dogs vs. controls (all P <= 0.011). In univariate analyses, HMGB-1 was
      significantly greater in non-survivors 46.67 ng/mL (8.94-84.73) compared to
      survivors 6.03 ng/mL (3.30-15.75), (P = 0.003). Neither HMGB-1 or the cytokines
      were associated with survival independent of illness severity as measured by the
      APPLE score, however.

PMID- 30105232
TI  - Skin cancer management-updates on Merkel cell carcinoma.
AB  - There are many different types of skin tumors in the World Health Organization
      (WHO) classification. The natural course and treatment varies according to the
      histological type. This review summarizes clinical experience for treatment
      decision. Contemporary radiotherapy and systemic therapy are improving. Landmark
      studies for basal cell and Merkel cell carcinomas (MCC) trigger further research
      and impetus for improving treatment outcome. Avelumab, nivolumab, pembrolizumab,
      ipilimumab appear to be promising for treatment of advanced MCCs and adjuvant
      trials are underway.

PMID- 30105234
TI  - Management of hormone-receptor positive human epidermal receptor 2 negative
      advanced or metastatic breast cancers.
AB  - Hormone therapy, rather than chemotherapy, is recommended for hormone-receptor
      positive (HR+), human epidermal receptor 2 negative (HER2-) advanced or
      metastatic breast cancer (A/MBC) according to the European Society of Medical
      Oncology (ESMO), American Society of Clinical Oncology (ASCO) and National
      Comprehensive Cancer Network (NCCN) guidelines, unless in visceral crisis in
      which chemotherapy is indicated. Hormonal monotherapy of selective estrogen
      receptor modulator (SERM) or selective estrogen receptor down-regulator (SERD),
      aromatase inhibitor (AI), or their combination as doublets, used to be the
      mainstay options as first-line (1L) therapy for most patients. More recently,
      combination targeted drugs plus AI or SERD (such as fulvestrant) has been
      extensively investigated in both 1L and second-line (2L) treatments of HR+ HER2-
      patients. Cyclin-D kinase 4/6 inhibitors (CDK4/6i) can halt tumor proliferation
      by blocking the ER related transcription signaling that drives the CDK4/6
      dependent cell cycle in HR+ tumors, and they work best together with AI or SERD.
      On the other hand, favorable results were reported from inhibition of m-TOR
      pathway, both in 2L setting when PI3K-AKT-mTOR pathway is frequently
      overexpressed, as well as in 1L setting. Currently, the major guidelines have all
      included CDK4/6i plus AI as a standard 1L therapy, while Everolimus plus AI, and
      CDK4/6i plus fulvestrant, are recommended 2L options. Selecting appropriate
      patients for such therapeutic options and harnessing the sequence of these new
      therapies in the new paradigm of managing HR+ HER2- A/MBC are the key priorities
      for future clinical research.

PMID- 30105226
TI  - Molecular Basis of Human Sperm Capacitation.
AB  - In the early 1950s, Austin and Chang independently described the changes that are
      required for the sperm to fertilize oocytes in vivo. These changes were
      originally grouped under name of "capacitation" and were the first step in the
      development of in vitro fertilization (IVF) in humans. Following these initial
      and fundamental findings, a remarkable number of observations led to
      characterization of the molecular steps behind this process. The discovery of
      certain sperm-specific molecules and the possibility to record ion currents
      through patch-clamp approaches helped to integrate the initial biochemical
      observation with the activity of ion channels. This is of particular importance
      in the male gamete due to the fact that sperm are transcriptionally inactive.
      Therefore, sperm must control all these changes that occur during their transit
      through the male and female reproductive tracts by complex signaling cascades
      that include post-translational modifications. This review is focused on the
      principal molecular mechanisms that govern human sperm capacitation with
      particular emphasis on comparing all the reported pieces of evidence with the
      mouse model.

PMID- 30105237
TI  - Dr. Cameron Turtle: the future of immunotherapy is bright!

PMID- 30105236
TI  - Dr. Joseph Siu-Kie Au: beyond immunotherapy-discovering new possibilities.

PMID- 30105238
TI  - Prof. R. Stephanie Huang: an expert in pharmacogenomics.

PMID- 30105233
TI  - Stereotactic body radiation therapy for lung, spine and oligometastatic disease:
      current evidence and future directions.
AB  - Stereotactic body radiation therapy (SBRT) also referred to as stereotactic
      ablative radiotherapy (SABR), is a technique which has emerged over the past two
      decades due to improvements in radiation technology. Unlike conventional external
      beam radiotherapy (cEBRT) which traditionally delivers radiation in small doses
      [approximately 2 Gray (Gy) per fraction] over several weeks, SBRT, typically
      delivered in one to eight fractions, is a technique whereby potentially ablative
      doses of radiotherapy (usually 7.5-20 Gy per fraction) can be delivered with
      steeper dose gradients and sub millimetre precision, minimising risk to
      surrounding normal tissues. The potential benefits of excellent tumor control
      with low toxicity has led to the increasing use of SBRT in a number of clinical
      situations. Due to compelling evidence, SBRT is now the treatment of choice for
      medically inoperable patients with peripherally located stage I non-small cell
      lung cancer (NSCLC). Controversy remains however as to its efficacy and safety
      for central or ultra-central lung tumors. The evidence base supporting the use of
      SBRT as a novel treatment for spinal metastases and oligometastases is rapidly
      expanding but challenges remain in these difficult patient populations. In an era
      where targeted therapy and improved systemic treatments for stage IV cancer have
      resulted in increased disease-free survival, and our knowledge of the
      oligometastatic state is ever expanding, using SBRT to treat metastatic disease
      and gain durable local control is increasingly desirable. Several randomized
      trials are currently underway and are sure to provide valuable information on the
      benefit and utility of SBRT across many tumor sites including early-stage NSCLC,
      spinal metastases and oligometastatic disease. Recognizing the evolving role of
      SBRT in clinical practice, this paper provides a critical review of recent
      developments in each of these areas particularly highlighting the challenges
      facing clinicians and discusses potential areas for future research.

PMID- 30105235
TI  - Precision oncology in liver cancer.
AB  - With the widespread adoption of molecular profiling in clinical oncology
      practice, many physicians are faced with making therapeutic decisions based upon
      isolated genomic alterations. For example, epidermal growth factor receptor
      tyrosine kinase inhibitors (TKIs) are effective in EGFR-mutant non-small cell
      lung cancers (NSCLC) while anti-EGFR monoclonal antibodies are ineffective in Ras
      mutant colorectal cancers. The matching of mutations with drugs aimed at their
      respective gene products represents the current state of "precision" oncology.
      Despite the great expectations of this approach, only a fraction of cancers
      responds to 'targeted' interventions, and many early responders will ultimately
      develop resistance to these agents. The underwhelming success of mutation-driven
      therapies across all cancer types is not due to an inability to detect genetic
      changes in tumors; rather a deficit in functional insight into the genomic
      alterations that give rise to each cancer. The Achilles heel of precision
      oncology thus remains the lack of a robust functional understanding of an
      individual cancer genome that then allows prediction of the best therapy and
      resultant outcome for that patient. Current practice focuses on one 'actionable'
      mutation at a time, while solid cancers typically possess many mutations that
      involve different cellular sub-populations within a tumor. No method or platform
      currently exists to guide the interpretation of these complex data, nor to
      accurately predict response to treatment. This problem is particularly germane to
      primary liver cancers (PLC), for which only a handful of targeted therapies have
      been introduced. Here, we will review strategies aimed at overcoming some of
      these challenges in precision oncology, using liver cancer as an example.

PMID- 30105239
TI  - A pursuit of better treatment in oncology: the 4th Hong Kong International
      Oncology Symposium 2017.

PMID- 30105240
TI  - Bioconversion of p-Tyrosol into Hydroxytyrosol under Bench-Scale Fermentation.
AB  - Tyrosol hydroxylating Pseudomonas strain was previously isolated from olive mill
      wastewaters-irrigated soil. In the present work, experimental design was used to
      study the bioconversion of tyrosol in laboratory fermenters aiming at the
      recovery of the highest yields of hydroxytyrosol. The effects of biocatalyst
      loading and tyrosol concentration were studied. The bioconversion yield reached
      86.9% (37.3 mM hydroxytyrosol) starting from a tyrosol concentration of 43 mM.
      Under these conditions, the specific productivity relative to the biocatalyst was
      4.78 MUM/min/g. The established model to predict bioconversion yield was
      validated in two bench-scale fermenters. At the downstream stage, the reaction
      product was recovered as a hydroxytyrosol rich solution after microfiltration and
      concentration under vacuum. Subsequent to this operation, hydroxytyrosol
      composition yielded 73.8% of the total dry matter.

PMID- 30105241
TI  - Antimicrobial Potential of Caffeic Acid against Staphylococcus aureus Clinical
      Strains.
AB  - Phenolic compounds constitute one of the most promising and ubiquitous groups
      with many biological activities. Synergistic interactions between natural
      phenolic compounds and antibiotics could offer a desired alternative approach to
      the therapies against multidrug-resistant bacteria. The objective of the
      presented study was to assess the antibacterial potential of caffeic acid (CA)
      alone and in antibiotic-phytochemical combination against Staphylococcus aureus
      reference and clinical strains isolated from infected wounds. The caffeic acid
      tested in the presented study showed diverse effects on S. aureus strains with
      the minimum inhibitory concentration (MIC) varied from 256 MUg/mL to 1024 MUg/mL.
      The supplementation of Mueller-Hinton agar (MHA) with 1/4 MIC of CA resulted in
      augmented antibacterial effect of erythromycin, clindamycin, and cefoxitin and to
      the lesser extent of vancomycin. The observed antimicrobial action of CA seemed
      to be rather strain than antibiotic dependent. Our data support the notion that
      CA alone exerts antibacterial activity against S. aureus clinical strains and has
      capacity to potentiate antimicrobial effect in combination with antibiotics. The
      synergy between CA and antibiotics demonstrates its potential as a novel
      antibacterial tool which could improve the treatment of intractable infections
      caused by multidrug-resistant strains.

PMID- 30105242
TI  - Comparison of LI-RADS v.2017 and ESGAR Guidelines Imaging Criteria in HCC
      Diagnosis Using MRI with Hepatobiliary Contrast Agents.
AB  - Purpose: The purpose of this study was to assess and compare diagnostic ability
      of LI-RADS (LR) v. 2017 and ESGAR guidelines in hepatocellular carcinoma (HCC)
      diagnosis using MRI with hepatobiliary contrast agents. Methods: Seventy
      pathologically confirmed lesions in 32 patients (24 males and 8 females) who had
      MRI with hepatobiliary contrast done before surgery or biopsy were reviewed
      retrospectively. Six lesions were <10mm, 31 lesions 10-19mm, and 33 lesions
      >=20mm. Two readers assessed all lesions according to LI-RADS v.2017 criteria and
      ESGAR consensus statement on liver MR imaging and clinical use of liver-specific
      contrast agents. Statistical analysis was performed to compare diagnostic ability
      of both guidelines including receiver operative curves (ROC) and area under curve
      (AUC). Results: For LR >= 4 sensitivity, specificity, accuracy, and AUC were 96%,
      75%, 88.6%, and 85.5, respectively. For LR5 they were 74%, 95%, 80%, and 84.5,
      respectively. For ESGAR criteria with major and additional features, they were
      88%, 75%, 84.3%, and 81.5, respectively. For ESGAR criteria only with major
      features they were 78%, 80%, 78.6%, and 79, respectively. AUC analysis revealed
      that overall diagnostic ability of LI-RADS was higher than ESGAR but the results
      did not show statistical significance. Conclusions: Both LI-RADS and ESGAR
      guidelines presented high diagnostic ability in HCC diagnosis of MRI studies with
      hepatobiliary contrast agents. More complex LI-RADS criteria performed better
      than ESGAR guidelines and it may justify extra effort that needs to be put in the
      report. However, the results were not statistically different and the simplicity
      of the ESGAR guidelines should also be taken into consideration.

PMID- 30105243
TI  - Effects of Low-Intensity Pulsed Ultrasound on Knee Osteoarthritis: A Meta
      Analysis of Randomized Clinical Trials.
AB  - Background: Osteoarthritis (OA) is a common degeneration disease characterized
      with joint pain. The aim of the present study was to systemically review the
      effects of LIPUS on pain relief and functional recovery in patients with knee
      osteoarthritis (OA). Methods: PubMed, Embase, and Cochrane Library were searched
      manually for researches on LIPUS treatment in patients with knee OA from 1945 to
      July 2017. Two investigators independently selected the studies according to the
      inclusion and exclusion criteria, extracted the concerned data, and assessed the
      included studies. Meta-analysis was performed to evaluate VAS, WOMAC, and
      ambulation speed between control and LIPUS groups. Results: Five studies were
      selected in this study. Compared with control group, LIPUS group received a
      decrease of pain intensity with moderate heterogeneity (-0.79, 95% CI, -1.57 to
      0.00; I2 = 65%, P = 0.04) by VAS and improvement in knee function by WOMAC (
      5.30, 95% CI, -2.88 to -7.71; I2 = 44%, P = 0.17). No significant improvement was
      found in ambulation speed (0.08 m/s, 95% CI, -0.02 to 0.18 m/s; I2 = 68%, P =
      0.03). Conclusion: The present study includes 5 high quality randomized
      controlled trials. The result indicated that LIPUS, used to treat knee OA without
      any adverse effect, had a beneficial effect on pain relief and knee functional
      recovery. More evidence is needed to prove whether LIPUS is effective in
      improving walking ability.

PMID- 30105244
TI  - Peroxisome Proliferator-Activated Receptor-gamma Prevents Cholesterol Gallstone
      Formation in C57bl Mice by Regulating Bile Acid Synthesis and Enterohepatic
      Circulation.
AB  - To investigate the role of the peroxisome proliferator-activated receptor-gamma
      (PPARgamma) in the progression of cholesterol gallstone disease (CGD), C57bl/6J
      mice were randomized to the following groups (n=7/group): L (lithogenic diet,
      LGD), LM (LGD+pioglitazone), CM (chow diet+pioglitazone), and NC (normal control,
      chow diet). Gallbladder stones were observed by microscopy. Histological
      gallbladder changes were assessed. Bile acids (BA) and cholesterol were measured
      in the serum, bile, and feces. Proteins and mRNA expression of genes involved in
      BA metabolism and enterohepatic circulation were assessed by western blotting and
      real-time RT-PCR. PPARgamma activation was performed in LO2 cell by lentivirus
      transfection and in Caco2 cell by PPARgamma agonist treatment. Downregulation of
      farnesoid X receptor (FXR) by small interference RNA (siRNA) was performed in L02
      cells and Caco2 cells, respectively. Results showed that pharmacological
      activation of PPARgamma by pioglitazone prevents cholesterol gallstone formation
      by increasing biliary BA synthesis and enterohepatic circulation. Activated
      PPARgamma induced the expression of genes involved in enterohepatic circulation
      and bile acid synthesis (like PCG1alpha, BSEP, MRP2, MRP3, MRP4, NTCP, CYP7A1,
      CYP27A1, ASBT, OSTalpha, and OSTbeta). Downregulation of FXR repressed expression
      of partial genes involved in BA enterohepatic circulation. These findings suggest
      a new function of PPARgamma in preventing CGD by handling BA synthesis and
      transport through a FXR dependent or independent pathway.

PMID- 30105245
TI  - Differences in Body Composition in Older People from Two Regions of Mexico:
      Implications for Diagnoses of Sarcopenia and Sarcopenic Obesity.
AB  - Background: Mexico is a country that is rich in ethnicity and cultural diversity,
      divided into three well-defined socioeconomic, ecological, and epidemiological
      areas. However, we do not know the influence that these factors may have on body
      composition. Therefore, this study was designed to assess body composition and
      compare appendicular skeletal muscle mass (ASM) in older people from two areas of
      the country. Methods: This is a cross-sectional study that included 430 subjects
      >=60 years of age from northwestern and central Mexico. Body composition,
      including ASM, was measured by dual-energy X-ray absorptiometry, while
      anthropometry, handgrip strength, demographic variables, health status/chronic
      conditions, and energy expenditure data were all included. Results: Men and women
      from the northwestern region had 5.9 kg and 3.8 kg more body fat, respectively,
      and 3.9 kg more as a group than their counterparts from central Mexico (p <=
      0.0001). While there were no significant differences across gender or region in
      terms of ASM, the older subjects from central Mexico had a significantly higher
      ASM index (ASMI) than the sample from the northwest. When ASM was adjusted for
      age, body weight, height, health status/chronic conditions, estimated energy
      expenditure, and demographic variables, the subjects from central Mexico had
      significantly higher adjusted mean values of ASM and ASMI than their counterparts
      from the northwest. Conclusion: Older people from two regions of Mexico had
      significantly different estimates of body composition. Our findings highlight the
      importance of regionalizing estimates of ASM and ASMI if they are to be used for
      diagnostic purposes. It is also important to emphasize that appendicular skeletal
      muscle mass, or the ASM index, should be adjusted for other associated biological
      variables.

PMID- 30105246
TI  - Kinetics of Targeted Phage Rescue in a Mouse Model of Systemic Escherichia coli
      K1.
AB  - Escherichia (E.) coli K1 strains remain common causative agents of neonatal
      sepsis and meningitis. We have isolated a lytic bacteriophage (PhiIK1) against E.
      coli strain IHE3034 and tested its specificity in vitro, as well as distribution
      and protective efficacy in vivo. The phage was shown to be specific to the K1
      capsular polysaccharide. In the lethal murine model, a high level of protection
      was afforded by the phage with strict kinetics. A single dose of 1 x 108 phage
      particles administered 10 and 60 minutes following the bacterial challenge
      elicited 100 % and 95 % survival, respectively. No mice could be rescued if phage
      administration occurred 3 hours postinfection. Tissue distribution surveys in the
      surviving mice revealed that the spleen was the primary organ in which
      accumulation of active PhiIK1 phages could be detected two weeks after phage
      administration. These results suggest that bacteriophages have potential as
      therapeutic agents in the control of systemic infections.

PMID- 30105247
TI  - The Dimensionless Squared Jerk: An Objective Parameter That Improves Assessment
      of Hand Motion Analysis during Simulated Shoulder Arthroscopy.
AB  - Purpose: Attempts to quantify hand movements of surgeons during arthroscopic
      surgery faced limited progress beyond motion analysis of hands and/or
      instruments. Surrogate markers such as procedure time have been used. The
      dimensionless squared jerk (DSJ) is a measure of deliberate hand movements. This
      study tests the ability of DSJ to differentiate novice and expert surgeons
      (construct validity) whilst performing simulated arthroscopic shoulder surgical
      tasks. Methods: Six residents (novice group) and six consultants (expert group)
      participated in this study. Participants performed three validated tasks
      sequentially under the same experimental setup (one performance). Each
      participant had ten performances assessed. Hand movements were recorded with
      optical tracking system. The DSJ, time taken, total path length, multiple
      measures of acceleration, and number of movements were recorded. Results: There
      were significant differences between novices and experts when assessed using
      time, number of movements with average and minimal acceleration threshold, and
      DSJ. No significant differences were observed in maximum acceleration, total path
      length, and number of movements with 10m/s2 acceleration threshold. Conclusion:
      DSJ is an objective parameter that can differentiate novice and expert surgeons'
      simulated arthroscopic performances. We propose DSJ as an adjunct to more
      conventional parameters for arthroscopic surgery skills assessment.

PMID- 30105248
TI  - Development of a New Molecular Marker for the Resistance to Tomato Yellow Leaf
      Curl Virus.
AB  - Tomato yellow leaf curl virus (TYLCV) responsible for tomato yellow leaf curl
      disease (TYLCD) causes a substantial decrease in tomato (Solanum lycopersicum L.)
      yield worldwide. The use of resistant variety as a sustainable management
      strategy has been advocated. Tremendous progress has been made in genetically
      characterizing the resistance genes (R gene) in tomato. Breeding tomato for TYLCV
      resistance has been based mostly on Ty-3 as a race-specific resistance gene by
      introgression originating from wild tomato species relatives. Improvement or
      development of a cultivar is achievable through the use of marker-assisted
      selection (MAS). Therefore, precise and easy use of gene-targeted markers would
      be of significant importance for selection in breeding programs. The present
      study was undertaken to develop a new marker based on Ty-3 gene sequence that can
      be used for MAS in TYLCV resistant tomato breeding program. The new developed
      marker was named ACY. The reliability and accuracy of ACY were evaluated against
      those of Ty-3 linked marker P6-25 through screening of commercial resistant and
      susceptible tomato hybrids, and genetic segregation using F2 population derived
      from a commercial resistant hybrid AG208. With the use of bioinformatics and DNA
      sequencing analysis tools, deletion of 10 nucleotides was observed in Ty-3 gene
      sequence for susceptible tomato variety. ACY is a co-dominant indel-based marker
      that produced clear and strong polymorphic band patterns for resistant plant
      distinguishing it from its susceptible counterpart. The obtained result
      correlates with 3:1 segregation ratio of single resistant dominant gene
      inheritance, which depicted ACY as gene-tag functional marker. This marker is
      currently in use for screening 968 hybrids varieties and one thousand breeding
      lines of tomato varieties stocked in Jiangsu Green Port Modern Agriculture
      Development Company (Green Port). So far, ACY has been used to identify 56
      hybrids and 51 breeding lines. These newly detected breeding lines were regarded
      as potential source of resistance for tomato breeding. This work exploited the
      sequence of Ty-3 and subsequently contributed to the development of molecular
      marker ACY to aid phenotypic selection. We thus recommend this marker to
      breeders, which is suitable for marker-assisted selection in tomato.

PMID- 30105250
TI  - Functions of the C2H2 Transcription Factor Gene thmea1 in Trichoderma harzianum
      under Copper Stress Based on Transcriptome Analysis.
AB  - Trichoderma spp. are important biocontrol filamentous fungi and have tremendous
      potential in soil bioremediation. In our previous studies, a C2H2 type
      transcription factor coding gene (thmea1) was cloned from a biocontrol agent T.
      harzianum Th-33; the encoded sequence of thmea1 contained 3 conserved C2H2
      domains with Swi5 and Ace2 in Saccharomyces cerevisiae. The thmea1 knockout
      mutant Deltathmea1 showed 12.9% higher copper tolerance than the wild-type Th33.
      To elucidate the function of thmea1 and its relationship with copper stress
      response, we conducted transcriptome sequencing and analysis of wild-type Th33
      and Deltathmea1 under 0.8 mM copper stress. A total of 1061 differentially
      expressed genes (DEGs) were identified between the two strains, all DEGs were
      assigned to KEGG pathway database, 383 DEGs were annotated in 191 individual
      pathways, and the categories of ribosomal protein synthesis and amino acid
      metabolism were the most highly enriched ones. Analysis of related DEGs showed
      that the expression levels of intracellular glutathione detoxification enzyme,
      heat shock proteins, and ribosomal proteins in Deltathmea1 were higher than that
      of the wild-type Th33, and the expression of metallothionein (MT) gene did not
      change. In addition, the expression levels of genes coding for proteins
      associated with the Ccc2p-mediated copper chaperone Atx1p transport of copper
      ions into the Golgi secretory pathway increased, as well as the copper amine
      oxidase (CuAO). These findings suggest that Thmea1 is a negative regulated factor
      of copper tolerance ability in T. harzianum. It does not show metallothionein
      expression activator activities as that of Ace2 in S. cerevisiae. We hypothesize
      that after T. harzianum has lost its thmea1 gene, the ability of cells to
      scavenge reactive oxygen species, mainly through the glutathione antioxidant
      system, is enhanced, whereas protein synthesis and repair and copper secretion
      increase under copper stress, which increases the ability of the mutant strain to
      tolerate copper stress.

PMID- 30105251
TI  - Coxiella burnetii Detected in Tick Samples from Pastoral Communities in Kenya.
AB  - Ticks are important disease vectors in Kenya with documented evidence of carriage
      of zoonotic pathogens. Coxiella burnetii is an important tick-borne pathogen that
      is underreported in Kenya and yet this infection likely contributes to
      undiagnosed febrile disease in pastoral communities. Archived human blood (278)
      and tick pool samples (380) collected from five pastoral communities in Kenya
      were screened for C. burnetii by PCR using primers targeting the transposon-like
      IS1111 region. All the human blood samples were negative for C. burnetii DNA.
      However, C. burnetii was detected in 5.53% (21/380) of the tick pools tested.
      Four of the twenty-one PCR positive samples were sequenced. The findings indicate
      that Coxiella burnetii was not present in the human blood samples tested.
      However, C. burnetii was detected in ticks from Mai Mahiu, Marigat, Ijara,
      Isiolo, and Garissa indicating a natural infection present in the tick vector
      that poses a risk to livestock and humans in these communities.

PMID- 30105252
TI  - Association between Participants' Characteristics, Patient-Reported Outcomes, and
      Clinical Outcomes in Youth with Sickle Cell Disease.
AB  - Background: Sickle cell disease (SCD) is a chronic debilitating illness. SCD
      related complications result in substantial impairment in quality of life (QOL).
      Our study objective was to assess the relationship of participants'
      characteristics, QOL, hydroxyurea adherence, and SCD-related clinical outcomes in
      youth with SCD. Procedure: A single-center cross-sectional study. Thirty-four
      youth with SCD enrolled from clinic between January and December 2015.
      Participants completed PROMIS(r) measures and (c)Modified Morisky Adherence
      Scale. Results: Participants had a mean age of 14.8 (SD 2.9) years and 41% were
      female. Participants' age correlated with fatigue (rs=0.48; P=0.006), pain
      (rs=0.32; P=0.07), and anxiety (rs=0.33; P=0.06) scores. Participants with
      chronic pain had worse upper extremity physical function (P=0.05), pain (P=0.04),
      anxiety (P=0.05), and depression (P=0.05). Males reported significantly higher
      hydroxyurea adherence (5.4 versus 3.6, P=0.02) compared to females. Participants
      with chronic pain had more frequent hospitalizations (P=0.02), emergency room
      visits (P=0.04), and longer total length of hospital stays over 12-month period
      (P=0.01). Conclusions: Older and female participants had worse QOL scores, and
      males reported higher hydroxyurea adherence. Participants with chronic pain
      reported significant impairment in different QOL domains and had increased
      healthcare utilization. Future longitudinal studies examining the relationship
      between participants' characteristics, QOL, hydroxyurea adherence, and SCD
      related clinical outcomes are needed.

PMID- 30105249
TI  - A Systematic Review of Long Noncoding RNAs in Hepatocellular Carcinoma: Molecular
      Mechanism and Clinical Implications.
AB  - Hepatocellular carcinoma (HCC) has the second highest mortality rate worldwide
      among all cancers. Previous studies have revealed the significant involvement of
      long noncoding RNAs (lncRNAs) in numerous human cancers including HCC. Both
      oncogenic and tumor repressive lncRNAs have been identified and implicated in the
      complex process of hepatocarcinogenesis. They can be further explored as
      prospective diagnostic, prognostic, and therapeutic markers for HCC. An in-depth
      understanding of lncRNAs' mechanism in HCC is therefore required to fully explore
      their potential role. In the current review, we will concentrate on the
      underlying function, molecular mechanisms, and potential clinical implications of
      lncRNA in HCC.

PMID- 30105253
TI  - Prognostic Significance of P16INK4a Expression in Penile Squamous Cell Carcinoma:
      A Meta-Analysis with Trial Sequential Analysis.
AB  - Background: Recently, P16INK4a expression has been shown to be correlated with
      cancer-specific survival (CSS) in penile squamous cell carcinoma (SCC).
      Therefore, we performed this meta-analysis to clarify the prognostic value of
      P16INK4a for penile SCC. Methods: A systematic search was performed in PubMed,
      Embase, and Web of Science to identify all relevant articles up to May 25, 2017.
      Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of included
      studies were pooled to estimate the prognostic value. Trial sequential analysis
      (TSA) was performed to assess the quantity and strength of survival evidence.
      Results: Five retrospective studies consisting of 323 cases were finally
      included. We found that P16INK4a positive expression was significantly associated
      with a better CSS of penile SCC (HR=0.45, 95%CI: 0.30-0.67, P<0.001). No
      heterogeneity or publication bias was noted among the included studies.
      Furthermore, TSA demonstrated that the findings were based on sufficient
      evidence. Conclusions: P16INK4a positive expression is independently associated
      with improved CSS for patients with penile SCC.

PMID- 30105254
TI  - A Comparison of the Immunostimulatory Effects of Polysaccharides from Tetraploid
      and Diploid Echinacea purpurea.
AB  - Polyploidization is an effective means of improving the active components and
      quality of secondary metabolism in medicinal plants. In the present study, we
      compared the immunostimulatory effects of crude polysaccharides from tetraploid
      and diploid Echinacea purpurea. The results showed that the carbohydrate contents
      of crude polysaccharide of tetraploid E. purpurea (CPE4) and diploid E. purpurea
      (CPE2) were 85.51% and 44.65%, respectively. 1H-nuclear magnetic resonance (NMR)
      spectroscopy and gel-permeation chromatography (GPC) analyses showed no major
      differences in the overall structure and molecular weight of polysaccharides
      between CPE4 and CPE2. However, some differences in the relative content of the
      same polysaccharides group were observed between CPE4 and CPE2. In in vitro
      tests, EP4 could stimulate lymphocyte proliferation and secretion of cytokines
      maximally at the concentration of 0.0312 mg/mL, and EP2 could stimulate
      lymphocyte proliferation and secretion of cytokines maximally at the
      concentration of 0.125 mg/mL. In in vivo tests, EP4 was more effective at
      promoting the proliferation of lymphocytes and secretion of cytokines in mice
      immunosuppressed by cyclophosphamide than EP2 at the same concentration. Taken
      together, these data demonstrated that the relative content of the partial
      polysaccharides group is increased, and the immunoregulatory effect is enhanced
      in tetraploid E. purpurea.

PMID- 30105255
TI  - Tinnitus Abnormal Brain Region Detection Based on Dynamic Causal Modeling and
      Exponential Ranking.
AB  - Dynamic Causal Modeling (DCM) has been extended for the analysis of
      electroencephalography (EEG) based on a specific biophysical and neurobiological
      generative model for EEG. Comparing to methods that summarize neural activities
      with linear relationships, the generative model enables DCM to better describe
      how signals are generated and better reveal the underlying mechanism of the
      activities occurring in human brains. Since DCM provides us with an approach to
      the effective connectivity between brain areas, with exponential ranking, the
      abnormality of the observed signals can be further located to a specific brain
      region. In this paper, a combination of DCM and exponential ranking is proposed
      as a new method aiming at searching for the abnormal brain regions which are
      associated with chronic tinnitus.

PMID- 30105258
TI  - Impact of Hypothermia and Oxygen Deprivation on the Cytoskeleton in Organ
      Preservation Models.
AB  - Ischemia reperfusion (IR) lesions are an unavoidable consequence of organ
      transplantation. Researching new therapeutics against these lesions requires the
      definition of early mechanisms. The cytoskeleton is composed of 3 types of
      filaments: microfilaments, intermediate filaments, and microtubules. We aimed to
      characterize the influence of preservation on their phenotype. In an in vitro
      model using primary human endothelial cells reproducing the conditions of organ
      preservation, two aspects were explored: (a) the impact of IR and cold ischemia
      time on each filament type, evaluating the roles of temperature, solution, and
      oxygen; and (b) the potential of cytoskeleton-mediated therapy to alleviate cell
      death. Results showed that intermediary filaments were unaffected, while
      microfilaments showed radical changes with disappearance of the structure
      replaced by a disorganized array of nodules; moreover, microtubules almost
      completely disappeared with time. Furthermore, temperature, and not oxygen
      deprivation or the solution, was the determining factor of the cytoskeleton's
      loss of integrity during preservation. Finally, pharmaceutical intervention could
      indeed preserve fiber structure but did not alter survival. Our work shows that
      improvement of preservation must include a more adapted temperature before
      considering oxygen, as it could profoundly improve cytoskeleton organization and
      thus cell fate. This highlights the importance of this structure for the
      development of new therapeutics and the definition of graft quality biomarkers.

PMID- 30105259
TI  - Genotypic and Phenotypic Relationship among Yield Components in Rice under
      Tropical Conditions.
AB  - The associations among yield-related traits and the pattern of influence on rice
      grain yield were investigated. This evaluation is important to determine the
      direct and indirect effects of various traits on yield to determine selection
      criteria for higher grain yield. Fifteen rice genotypes were evaluated under
      tropical condition at five locations in two planting seasons. The experiment was
      laid out in a randomized complete block design with three replications across the
      locations. Data were collected on vegetative and yield components traits. The
      pooled data based on the analysis of variance revealed that there were
      significant differences (p < 0.001) among the fifteen genotypes for all the
      characters studied except for panicle length and 100-grain weight. Highly
      significant and positive correlations at phenotypic level were observed in grain
      weight per hill (0.796), filled grains per panicle (0.702), panicles per hill
      (0.632), and tillers per hill (0.712) with yield per hectare, while moderate
      positive correlations were observed in flag leaf length to width ratio (0.348),
      days to flowering (0.412), and days to maturity (0.544). By contrast, unfilled
      grains per panicle (-0.225) and plant height (-0.342) had a negative significant
      association with yield per hectare. Filled grains per panicle (0.491) exhibited
      the maximum positive direct effect on yield followed by grain weight per hill
      (0.449), while unfilled grain per panicle (-0.144) had a negative direct effect.
      The maximum indirect effect on yield per hectare was recorded by the tillers per
      hill through the panicles per hill. Therefore, tillers per hill, filled grains
      per panicle, and grain weight per hill could be used as selection criteria for
      improving grain yield in rice.

PMID- 30105257
TI  - The Incidence and Risk Factors of Acute Kidney Disease after Total Knee
      Arthroplasty with Early Postoperative Volume Supplement.
AB  - Background: Etiology of acute kidney disease (AKD) after total knee arthroplasty
      (TKA) was considered as multifactorial. However, the role of early postoperative
      volume supplement in AKD rate has not been investigated. The purpose of this
      study was to evaluate the incidence and risk factors of AKD in patients with
      early volume supplement following TKA. Methods: This was a retrospective study
      with 458 patients who underwent unilateral TKA. All the patients received 6%
      tetrastarch, 7.5ml/kg, early in the postoperative period. Postoperative AKD was
      defined as the postoperative creatinine level >= 1.5 times compared with
      preoperative data. Potential variables associated with AKD were analyzed by
      multivariate logistic regression model to identify the AKD risk factors in TKA
      patients after early postoperative volume supplement. Results: The AKD rate was
      3.3% (15 patients) in all patients. Age (OR = 1.09; P = .031) and coronary artery
      disease (CAD) (OR = 3.63; P = .034) were associated with increased risk of
      development of postoperative AKD. Other comorbidities as hypertension, diabetes,
      and CKD were not statistically significant risk factors. Conclusion: Our study
      demonstrated that age and CAD were independent risk factors of AKD in TKA
      patients. However, the common risk factors as hypertension, diabetes, and CKD
      were not significantly associated with AKD after TKA if early postoperative
      supplement of tetrastarch is administered.

PMID- 30105256
TI  - Changes in Serum Electrolytes, ECG, and Baroreflex Sensitivity during Combined
      Pituitary Stimulation Test.
AB  - The mechanisms by which hypoglycemia increases cardiovascular mortality remain
      unclear. The aim of the study is to investigate changes in serum electrolytes,
      norepinephrine concentrations, electrocardiography, and baroreflex sensitivity
      (BRS) and associations between corrected QT (QTc) intervals and the changes in
      serum electrolytes during combined pituitary stimulation test (CPST). We
      recruited the subjects who were admitted to the Gyeongsang National University
      Hospital to undergo CPST between September 2013 and December 2014. Participants
      were 12 patients suspected of having hypopituitarism. Among 12 patients, cardiac
      arrhythmia in two patients occurred during hypoglycemia. There were significant
      differences in serum levels of potassium (P < 0.001), sodium (P = 0.003),
      chloride (P = 0.002), and calcium (P = 0.017) at baseline, hypoglycemia, and 30
      and 120 minutes after hypoglycemia. Also, there was a significant increase in
      heart rate (P = 0.004), corrected QT (QTc) interval (P = 0.008), QRS duration (P
      = 0.021), and BRS (P = 0.005) at hypoglycemia, compared to other time points
      during CPST. There was a positive association between QTc intervals and serum
      sodium levels (P < 0.001) in 10 patients who did not develop arrhythmia during
      CPST. This study showed that there were significant changes in serum levels of
      potassium, sodium, chloride, and calcium, as well as heart rate, QTc interval,
      QRSd, and BRS during CPST. It was revealed that QTc intervals had a significant
      association with concentrations of sodium.

PMID- 30105260
TI  - Age-Related Changes of Elastic Fibers in Shoulder Capsule of Patients with
      Glenohumeral Instability: A Pilot Study.
AB  - Background: Recurrent shoulder dislocations occur much more frequently in
      adolescents than in the older population but a clear explanation of this
      incidence does not exist. The aim of the present study was to define the age
      related distribution of the elastic fibers (EFs) in the shoulder capsule's
      extracellular matrix as a factor influencing shoulder instability. Materials and
      Methods: Biopsy specimens were obtained from the shoulder capsule of patients
      divided preoperatively into three groups: Group 1 consisted of 10 male patients
      undergoing surgery for unidirectional traumatic anterior instability (TUBS);
      Group 2 consisted of 10 male patients undergoing surgery for multidirectional
      instability (MDI); Group 3 represents the control, including 10 patients with no
      history of instability. In addition to the group as a whole, specific subgroups
      were analyzed separately on the basis of the age of subjects: > 22 or < to 22
      years. All the samples were analyzed by histochemical (Weigert's resorcinol
      fuchsin and Verhoeff's iron hematoxylin), immunohistochemical (monoclonal
      antielastin antibody), and histomorphometric methods. Results: Both the elastin
      density and the percentage of area covered by EFs were significantly higher in
      younger subjects (<22 years old). Furthermore, the elastin density and the
      percentage of area covered by EFs were significantly higher in specimens of group
      of patients affected by multidirectional shoulder instability in comparison to
      the other two groups. Conclusion: Data of the present study confirmed the
      presence of an age-related distribution of EFs in the human shoulder capsule. The
      greater amount of EFs observed in younger subjects and in unstable shoulders
      could play an important role in predisposing the joint to first dislocation and
      recurrence.

PMID- 30105261
TI  - Overexpression of Salusin-alpha Inhibits Vascular Intimal Hyperplasia in an
      Atherosclerotic Rabbit Model.
AB  - Inhibiting vascular endothelial foam is the focus of clinical attention. Using
      SonoVue (an ultrasound contrast agent), the salusin-alpha gene was transfected
      into the arterial intima of an atherosclerotic rabbit model induced by a high-fat
      diet in this study. Subsequently the model of blood lipid indexes, the
      pathological structure of the intima, and changes in molecules regulating
      atherosclerosis were investigated. The high-density lipoprotein C and
      apolipoprotein A values in the salusin-alpha gene overexpression (P) group were
      higher than those in the salusin-alpha gene interference (RP) group (P < 0.05),
      whereas the total cholesterol, low-density lipoprotein C, and apolipoprotein B
      values were reversed. Rabbits in the P group showed significantly thinner
      vascular intimal thickness than that of other experimental groups (P < 0.05). The
      expression of positive regulators of atherosclerosis (ABCA1, ABCG1) was higher in
      the P group than that in the RP group (P < 0.05), and the opposite effect was
      observed for negative regulators (ACAT1, CD36). Thus, our results showed that the
      overexpression of salusin-alpha gene inhibited the proliferation of the vascular
      intima, thereby throwing some light on understanding the mechanism how salusin
      alpha gene expression interfered with the foaming of vascular intimal cells.

PMID- 30105262
TI  - Investigation of MicroRNA in Mitochondrial Apoptotic Pathway in Systemic Lupus
      Erythematosus.
AB  - Background: Accumulating evidence indicates that microRNAs play a pivotal role in
      the pathogenesis of systemic lupus erythematosus (SLE). This study tested the
      hypothesis that microRNA is associated with the mitochondrial apoptotic pathway
      in patients with SLE. Methods: Thirteen patients were in the clinical comparison
      study and microRNA study and overall 19 patients in the study of intracellular
      protein. Levels of microRNAs were determined by miRNeasy kit in 13 patients with
      SLE and 29 volunteer normal controls. Intracellular levels of caspase-9, caspase
      10, MAVS, MDA5, and pIRF7 in mononuclear cells from 19 patiens and the SLE
      disease activity index (SLEDAI) were determined in all SLE patients. Correlation
      analyses were performed among microRNAs, intracellular adaptor proteins, and
      caspase levels and mean SLEDAI. Results: The DeltaCT, defined by test reading
      difference between the target and the internal control microRNA (miR-451a), of
      miR-21-5p, miR-150-5p, and miR221-3p were significantly higher in plasma from SLE
      patients than in normal controls. miR-150-5pDeltaCT was positively correlated
      with both CRP and SLEDAI value. miR-150-5pDeltaCT was negatively associated with
      MAVS 70 kD. Caspase-10 protein levels were negatively associated with plasma miR
      22-3pDeltaCT and miR-21-5pDeltaCT levels. Conclusions: Our study confirmed the
      hypothesis that these microRNAs were associated with the mitochondrial apoptotic
      pathway in SLE. miR-150-5pDeltaCT was positively associated with SLE disease
      activity and it was negatively correlated with MAVS 70 kD, which may facilitate
      viral survival and further enhance inflammation. On the other hand, miR-22
      3pDeltaCT and miR-21-5pDeltaCT, were negatively correlated with caspase-10
      levels, which may repress extrinsic apoptosis and increase cell survival.

PMID- 30105264
TI  - Neutrophilic Asthma Is Associated with Increased Airway Bacterial Burden and
      Disordered Community Composition.
AB  - Neutrophilic asthma (NA) is an important asthma inflammatory phenotype associated
      with disease severity, airflow limitation, and steroid resistance, and its
      mechanism is still uncertain. Evidences suggest a potential role for bacteria in
      its pathogenesis, but, so far, this remains poorly understood. We sought to
      investigate airway bacterial burden, community composition, and inflammatory
      response in NA. Fifty-four stable asthmatics without infection were enrolled and
      separated into either NA group (n = 20) or non-NA group (n = 34). Subject
      demographics, Asthma Control Test (ACT) scores, medications, and pulmonary
      functions were documented. Sputum cytology, airway bacterial burden, microbial
      community composition, and inflammatory cytokines were assessed. The total airway
      bacterial burden was significantly increased in subjects with NA versus non-NA
      and was positively correlated with the sputum neutrophil percentage. Airway
      neutrophilia was associated with less airway bacterial community richness and
      diversity, along with a distinct community composition. In patients with NA,
      bacteria in phylum Proteobacteria, especially Haemophilus spp. and Moraxella
      spp., showed significant increases in both actual loads and relative abundances,
      while bacteria in phyla Firmicutes, Actinobacteria, and Saccharibacteria showed
      decreased relative abundances compared with non-NA. Patients with NA demonstrated
      higher levels of interleukin-1beta (IL-1beta), IL-6, IL-8, IL-12, IL-17A, and
      tumor necrosis factor-alpha (TNF-alpha) in sputum samples compared with non-NA.
      Increased bacterial burden and distinct microbiota composition were the key
      characters of neutrophilic phenotype in asthma, accompanied by excessive airway
      inflammation. Understanding the relationship between airway microbiota and
      neutrophilic inflammation may help in treatment and management of asthma, such as
      targeting airway microbiota.

PMID- 30105263
TI  - Green Tea Catechins: Their Use in Treating and Preventing Infectious Diseases.
AB  - Green tea is one of the most popular drinks consumed worldwide. Produced mainly
      in Asian countries from the leaves of the Camellia sinensis plant, the potential
      health benefits have been widely studied. Recently, researchers have studied the
      ability of green tea to eradicate infectious agents and the ability to actually
      prevent infections. The important components in green tea that show antimicrobial
      properties are the catechins. The four main catechins that occur in green tea are
      (-)-epicatechin (EC), (-)-epicatechin-3-gallate (ECG), (-)-epigallocatechin
      (EGC), and (-)-epigallocatechin-3-gallate (EGCG). Of these catechins, EGCG and
      EGC are found in the highest amounts in green tea and have been the subject of
      most of the studies. These catechins have been shown to demonstrate a variety of
      antimicrobial properties, both to organisms affected and in mechanisms used.
      Consumption of green tea has been shown to distribute these compounds and/or
      their metabolites throughout the body, which allows for not only the possibility
      of treatment of infections but also the prevention of infections.

PMID- 30105265
TI  - Quality of Life after an Episode of Severe Maternal Morbidity: Evidence from a
      Cohort Study in Brazil.
AB  - Objective: To assess quality of life (QOL) in women who experienced a severe
      maternal morbidity (SMM) event and associated factors, in comparison to those who
      did not. Study Design: Retrospective cohort study performed at the maternity of
      the University of Campinas in Brazil, including 801 women with or without SMM,
      within 6 months to 5 years after delivery. Women were interviewed by phone and
      data were electronically stored, using the Brazilian version of the SF36 to
      assess women's self-perception of quality of life. To analyze a possible
      relationship between SMM and perceived impairment in quality of life, chi2 and
      Fisher's Exact tests were used. Multiple analysis using Generalized Linear Models
      was applied to identify factors independently associated with the general health
      score. The main outcome measures were general and domain-specific SF36 scores on
      quality of life. Results: Maternal morbidity conditions were associated with
      lower scores of patient perceptions of quality of life in the following domains:
      physical functioning, role-limiting physical, pain, and general health status. A
      lower level of school education, not having a partner, caesarean section, and
      history of previous clinical conditions were associated with a worse perception
      of general health and quality of life. Conclusion: Health professionals should
      know the association between life conditions, previous chronic health conditions,
      and SMM for women during prenatal care to beyond 42 weeks postpartum.
      Longitudinal and interdisciplinary actions should be put into practice to provide
      healthcare for these women, with special emphasis on the effective reduction in
      health inequities.

PMID- 30105266
TI  - Select Biomarkers on the Day of Anterior Cruciate Ligament Reconstruction Predict
      Poor Patient-Reported Outcomes at 2-Year Follow-Up: A Pilot Study.
AB  - Background: The majority of patients develop posttraumatic osteoarthritis within
      15 years of anterior cruciate ligament (ACL) injury. Inflammatory and
      chondrodegenerative biomarkers have been associated with both pain and the
      progression of osteoarthritis; however, it remains unclear if preoperative
      biomarkers differ for patients with inferior postoperative outcomes.
      Hypothesis/Purpose: The purpose of this pilot study was to compare biomarkers
      collected on the day of ACL reconstruction between patients with "good" or "poor"
      2-year postoperative outcomes. We hypothesized that inflammatory cytokines and
      chondrodegenerative biomarker concentrations would be significantly greater in
      patients with poorer outcomes. Study Design: Prospective cohort design. Methods:
      22 patients (9 females, 13 males; age = 19.5 +/- 4.1 years; BMI = 24.1 +/- 3.6
      kg/m2) previously enrolled in a randomized trial evaluating early anti
      inflammatory treatment after ACL injury. Biomarkers of chondrodegeneration and
      inflammation were assessed from synovial fluid (sf) samples collected on the day
      of ACL reconstruction. Participants completed Knee Injury and Osteoarthritis
      Outcome Score (KOOS) and International Knee Documentation Committee (IKDC)
      questionnaires two years following surgery. Patients were then categorized based
      on whether their KOOS Quality of Life (QOL) score surpassed the Patient
      Acceptable Symptom State (PASS) threshold of 62.5 points or the IKDC PASS
      threshold of 75.9 points. Results: Patients that failed to reach the QOL PASS
      threshold after surgery (n = 6, 27%) had significantly greater sf interleukin-1
      alpha (IL-1alpha; p = 0.004), IL-1 receptor antagonist (IL-1ra; p = 0.03), and
      matrix metalloproteinase-9 (MMP-9; p = 0.01) concentrations on the day of
      surgery. Patients that failed to reach the IKDC PASS threshold (n = 9, 41%) had
      significantly greater sf IL-1alpha (p = 0.02). Conclusion: These pilot data
      suggest that initial biochemical changes after injury may be an indicator of poor
      outcomes that are not mitigated by surgical stabilization alone. Biological
      adjuvant treatment in addition to ACL reconstruction may be beneficial; however,
      these data should be used for hypothesis generation and more definitive
      randomized clinical trials are necessary.

PMID- 30105267
TI  - Comment on "Discussion on the Timing of Balloon Occlusion of the Abdominal Aorta
      during a Caesarean Section in Patients with Pernicious Placenta Previa
      Complicated with Placenta Accreta".

PMID- 30105269
TI  - Weight Loss in Parkinson's Disease: The Relationship with Motor Symptoms and
      Disease Progression.
AB  - Objectives: To determine the prevalence of weight loss (WL) in PD patients, its
      relationship to the severity of motor manifestations and appetite changes.
      Methods: 144 PD patients and 120 controls were evaluated in a single session. All
      subjects were asked about changes in body weight and appetite. PD patients were
      examined with the UPDRS-III and the Hoehn and Yahr (HY) scales. Subscores of
      tremor, bradykinesia /rigidity, and non-dopaminergic symptoms (NDS) were analyzed
      individually. Multivariable logistic regression analysis was used to determine an
      association between WL and PD motor manifestations. Results: 48.6 % of PD
      patients presented WL compared to 20.8 % of controls (p < 0.001). Weight losers
      were significantly older and had longer disease duration, higher scores in HY
      stages, UPDRS-III, and NDS-subscore. Multivariable logistic regression analysis
      demonstrated that WL was associated with NDS-subscore (p= 0.002; OR: 1.33) and
      older age (p= 0.037; OR: 1.05). Appetite in PD cases losing weight was unchanged
      (35.7 %), decreased (31.4 %), or even increased (32.9). Conclusions: Our results
      showed that WL occurs in almost half of PD patients and it is largely the
      consequence of disease progression rather than involuntary movements or a
      decrease in food intake.

PMID- 30105268
TI  - The Thomsen-Friedenreich Antigen-Specific Antibody Signatures in Patients with
      Breast Cancer.
AB  - Alterations in the glycosylation of serum total immunoglobulins show these
      antibodies to have a diagnostic potential for cancer but the disease-related Abs
      to the tumor-associated antigens, including glycans, have still poorly been
      investigated in this respect. We analysed serum samples from patients with breast
      carcinoma (n = 196) and controls (n = 64) for the level of Thomsen-Friedenreich
      (TF) antigen-specific antibody isotypes, their sialylation, interrelationships,
      and the avidity by using ELISA with the synthetic TF-polyacrylamide conjugate as
      an antigen and the sialic acid-specific Sambucus nigra agglutinin (SNA) and
      ammonium thiocyanate as a chaotrope. An increased sialylation of IgG and IgM, but
      a lower SNA reactivity of IgA TF antibodies, and a higher level and avidity of
      the TF-specific IgA were found in cancer patients. Other cancer-related
      signatures were the highly significant increase of the IgG/IgA ratio and the very
      low SNA/IgA index in cancer, including patients with an early stage of the
      disease. These changes showed a good diagnostic potential with about 80%
      accuracy. Thus, the level of naturally occurring anti-TF antigen antibodies,
      their sialylation profile, isotype distribution, and avidity displayed cancer
      specific changes that could serve as novel noninvasive Ab-based biomarkers for
      early breast cancer.

PMID- 30105270
TI  - Physical Activity and Health-Related Fitness of Adolescents within the Juvenile
      Justice System.
AB  - Background: The purpose of this study was to examine the physical activity
      patterns and health-related fitness levels of adolescents within the Juvenile
      Justice System. Methods: Participants included 68 adolescents (Mean age = 17.1 +/
      1.0 years) in two secure Juvenile Justice correctional facilities in the Western
      USA. Moderate-to-vigorous physical activity (MVPA) was monitored for one week
      using the ActiGraph GT9X accelerometer. Health-related fitness was measured using
      the FITNESSGRAM test battery. Results: Adolescents averaged 43.3+/-21.6 minutes
      of MVPA per weekday compared to 42.7+/-27.5 per weekend day. During school hours,
      adolescents accumulated 17.1+/-9.0 minutes of MVPA compared to 5.9+/-3.4 minutes
      before school and 21.0+/-13.6 minutes after school. Adolescents averaged 18.9+/
      11.0 push-ups, 44.5+/-26.4 curl-ups, 34.7+/-24.8 PACER laps, and 22.1%+/-10.0%
      body fat. Conclusions: Adolescents within the Juvenile Justice System are falling
      short of the recommended 60 minutes of MVPA per day and 30 minutes of MVPA during
      school and also need to improve their health-related fitness, especially
      cardiorespiratory endurance.

PMID- 30105271
TI  - Antibacterial and Antibiofilm Activities of Nonpolar Extracts of Allium
      stipitatum Regel. against Multidrug Resistant Bacteria.
AB  - The present study assessed the in vitro antibacterial and antibiofilm potential
      of hexane (ASHE) and dichloromethane (ASDE) extracts of Allium stipitatum
      (Persian shallot) against planktonic cells and biofilm structures of clinically
      significant antibiotic resistant pathogens, with a special emphasis on
      methicillin-sensitive Staphylococcus aureus (MSSA), methicillin-resistant S.
      aureus (MRSA), and emerging pathogens, Acinetobacter baumannii and
      Stenotrophomonas maltophilia. Antibacterial activities were determined through
      disk diffusion, minimum inhibitory concentration (MIC), minimum bactericidal
      concentration (MBC), time-kill kinetics, and electron microscopy. Antibiofilm
      activity was assessed by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfo-phenyl)-2H
      tetrazolium-5-carboxanilide] reduction assay and by confocal laser scanning
      microscopy (CLSM). The zone of inhibition ranged from 13 to 33 mm, while the MICs
      and MBCs ranged from 16 to 1024 MUg mL-1. Both ASHE and ASDE completely
      eradicated overnight cultures of the test microorganisms, including antibiotic
      resistant strains. Time-kill studies showed that the extracts were strongly
      bactericidal against planktonic cultures of S. aureus, MRSA, Acinetobacter
      baumannii, and S. maltophilia as early as 4 hours postinoculation (hpi). ASHE and
      ASDE were shown to inhibit preformed biofilms of the four biofilm phenotypes
      tested. Our results demonstrate the potential therapeutic application of ASHE and
      ASDE to inhibit the growth of gram-positive and gram-negative biofilms of
      clinical significance and warrant further investigation of the potential of A.
      stipitatum bulbs against biofilm-related drug resistance.

PMID- 30105272
TI  - Current Visceral Leishmaniasis Research: A Research Review to Inspire Future
      Study.
AB  - Visceral leishmaniasis (VL), one of the deadliest parasitic diseases in the
      world, causes more than 50,000 human deaths each year and afflicts millions of
      people throughout South America, East Africa, South Asia, and Mediterranean
      Region. In 2015 the World Health Organization classified VL as a neglected
      tropical disease (NTD), prompting concentrated study of the VL epidemic using
      mathematical and simulation models. This paper reviews literature related to
      prevalence and prevention control strategies. More than thirty current research
      works were reviewed and classified based on VL epidemic study methods, including
      modeling approaches, control strategies, and simulation techniques since 2013. A
      summarization of these technical methods, major findings, and contributions from
      existing works revealed that VL epidemic research efforts must improve in the
      areas of validating and verifying VL mathematical models with real-world epidemic
      data. In addition, more dynamic disease control strategies must be explored and
      advanced simulation techniques must be used to predict VL pandemics.

PMID- 30105273
TI  - Rapid Onset of Inflammatory Bowel Disease after Receiving Secukinumab Infusion.
AB  - Secukinumab, an interleukin (IL)-17A antagonist, was associated with disease
      exacerbations in Crohn's disease, and de novo cases of inflammatory bowel disease
      (IBD) have been reported in studies of rheumatoid diseases. However, there has
      been no detailed report demonstrating the linkage between secukinumab therapy and
      new-onset IBD. We present a unique case of rapid-onset fulminant colitis after
      receiving 1 dose of secukinumab infusion followed by improvement with combination
      antibiotics, corticosteroids, and calcineurin inhibition. Health care providers
      should be aware of the possible association between IL-17 antagonist therapy and
      the risk of developing new-onset fulminant IBD.

PMID- 30105274
TI  - Esophageal and Gastroduodenal Hemorrhagic Necrosis: A Unique Finding in the
      Setting of Septic Shock and Vasopressor Use.
AB  - Esophageal and gastroduodenal necrosis are rare conditions with poor prognosis.
      We describe a case that was diagnosed with upper endoscopy in the setting of
      severe septic shock. To our knowledge, this is the first case in which esophageal
      and gastroduodenal necrosis occurred simultaneously in this setting. We discuss
      the pathophysiology, diagnostic approach, and treatment options of this rare
      entity.

PMID- 30105275
TI  - Ultrasound-Mediated Gene Therapy in Swine Livers Using Single-Element, Multi
      lensed, High-Intensity Ultrasound Transducers.
AB  - We have achieved significant enhancement of gene delivery into livers of large
      animals using ultrasound (US)-targeted microbubble (MB) destruction methods. An
      infusion of pGL4 (encoding a luciferase reporter gene) plasmid DNA (pDNA) and MBs
      into a portal-vein segmental branch of a porcine liver was exposed to US for 4
      min. Therapeutic US induced cavitation of MBs to temporarily permeabilize the
      vascular endothelium and cell membranes, allowing entry of pDNA. We obtained a 64
      fold enhancement in luciferase expression in pig livers compared to control
      without US using an unfocused, dual-element transducer (H105, center frequency
      [fc] = 1.10 MHz) at 2.7 MPa peak negative pressure (PNP). However, input
      electrical energy was limited, and modified transducers were designed to have
      spherical (H185A, fc = 1.10 MHz) or cylindrical foci (H185B, fc = 1.10 MHz;
      H185D, fc = 1.05 MHz) to enhance PNP output. The revised transducers required
      less electrical input to achieve 2.7 MPa PNP compared to H105, thereby allowing
      PNP outputs of up to 6.2 MPa without surpassing the piezo-material limitations.
      Subsequently, luciferase expression significantly improved up to 9,000-fold
      compared to controls with minor liver damage. These advancements will allow us to
      modify our current protocols toward minimally invasive US gene therapy.

PMID- 30105277
TI  - Academic performance data of undergraduate students' in 23 programmes from a
      private University in Nigeria.
AB  - The quality of teaching and learning in higher education in many developing
      countries can be improved as institutions in this region adopt evidence-based
      practices that emphasize empirical measurements, observations, analysis and
      reports of learning outcomes. This article presents and analyses data on the
      academic performances of undergraduate students for duration of three semesters
      across the three major colleges of Landmark University, a private University in
      Nigeria. The colleges include the college of Agricultural Sciences (CAS), college
      of Business and Social Sciences (CBSS), and the college of Science and
      Engineering (CSE). Furthermore, population samples of 82, 577 and 812
      undergraduates were selected randomly from CAS, CBSS and CSE respectively;
      totaling a population of sample of 1471 undergraduates from all academic levels
      (200L-500L) with the exception of first year students. The random selection was
      drawn from three consecutive semesters- the first and second semesters of
      academic 2016/2017 session and first semester of 2017/2018 academic session. The
      cumulative GPA of the sample population of students for the semester highlighted
      was obtained from the Centre for Systems and Information Services Units of the
      University. Motivated by the need to promote evidence-based research in academic
      excellence, a spread-sheet containing the detailed dataset is attached to this
      article. The descriptive statistics and frequency distributions of academic
      performance data are presented in with the use of tables and graphs for easy data
      interpretations. The data provided in this article supports the goal of a
      regional policy towards the realization of qualitative sustainable education.

PMID- 30105276
TI  - Loss of RANKL in osteocytes dramatically increases cancellous bone mass in the
      osteogenesis imperfecta mouse (oim).
AB  - Osteogenesis imperfecta (OI) is characterized by osteopenia and bone fragility,
      and OI patients during growth often exhibit high bone turnover with the net
      result of low bone mass. Recent evidence shows that osteocytes significantly
      affect bone remodeling under physiological and pathological conditions through
      production of osteoclastogenic cytokines. The receptor activator of nuclear
      factor kappa-B ligand (RANKL) produced by osteocytes for example, is a critical
      mediator of bone loss caused by ovariectomy, low-calcium diet, unloading and
      glucocorticoid treatment. Because OI bone has increased density of osteocytes and
      these cells are embedded in matrix with abnormal type I collagen, we hypothesized
      that osteocyte-derived RANKL contributes to the OI bone phenotype. In this study,
      the conditional loss of RANKL in osteocytes in oim/oim mice (oim-RANKL-cKO)
      resulted in dramatically increased cancellous bone mass in both the femur and
      lumbar spine compared to oim/oim mice. Bone cortical thickness increased
      significantly only in spine but ultimate bone strength in the long bone and spine
      was minimally improved in oim-RANKL-cKO mice compared to oim/oim mice.
      Furthermore, unlike previous findings, we report that oim/oim mice do not exhibit
      high bone turnover suggesting that their low bone mass is likely due to defective
      bone formation and not increased bone resorption. The loss of osteocyte-derived
      RANKL further diminished parameters of formation in oim-RANKL-cKO. Our results
      indicate that osteocytes contribute significantly to the low bone mass observed
      in OI and the effect of loss of RANKL from these cells is similar to its systemic
      inhibition.

PMID- 30105278
TI  - Evaluation of indoor air quality and its symptoms in office building - A case
      study of Mashhad, Iran.
AB  - Air pollution sources in indoor area are one of the main factors for reducing
      indoor air quality of locations. In the current research, factors affecting
      indoor air quality and its symptoms are evaluate as case study in an office
      building in Mashhad (Iran). In order to conduct this descriptive-analytical
      study, gas pollutants affecting indoor air quality were determined using portable
      analysis systems. Alberta Indoor Air Quality Toolkit was used in order to study
      sick building syndrome. Findings indicated that 21% of staffs viewed labor
      environment conditions as inappropriate and they were mostly compliant about
      feeling of dusty air, fatigue and headache. In addition, findings showed that O3,
      VOC, PM10, PM2.5, CO, CO2 parameters, Formaldehyde, temperature, sound and
      humidity were at standard level. Indicators of indoor air quality, in addition to
      the stress and depression interference on employee performance and satisfaction
      were at acceptable level.

PMID- 30105279
TI  - Microbial contamination data of keypad and touch screen of cell phones among
      hospital and non-hospital staffs - A case study: Iran.
AB  - Microorganisms live almost everywhere, they are even present on inanimate objects
      such as Mobile phones, as a result contaminates our body. The main purpose of
      this study was tantamount to compare microbial contamination of keypad and touch
      screen mobile cell phones between hospital and non-hospital staffs. Samples were
      collected from 456 cell phones of hospital and non-hospital. Microbial swab
      samples were taken from 1 cm2 of surface from each cell phone, and incubated on
      Brain Heart Infusion agar media at 37.5  degrees C for 24 h. Isolated
      microorganisms were grown aerobically on 55% defibrinated Sheep Blood and eosin
      methylene blue agar media at 37.5  degrees C for 48 h. In present study the
      antibiotic microorganism-resistant could not be observed. Overall, 456 cell
      phones were collected: 240 (52.63%) from hospital staff (nurses), 216 (47.36%)
      from non-hospital staff (health care worker outside the hospital). The result
      indicates that the bacterial contamination of phones used by all of different
      investigated groups was lower in touch screen devices than keypad devices and the
      contamination was found more in hospital staff cellphone than non-hospital
      staff's cell device. Woman's cell also has a few colonies rather than man's cell
      phones. The dominant microorganisms in the hospital staff were,
      Enterobacteriaceae, Bacillus species, especially Gram-positive bacteria
      sporulated and staphylococcal negative coagulase, respectively. Cell phones could
      be a serious threat to the spread of cross-infection in hospitals, therefore
      development of hand hygiene and cell phone cleaning guidelines is needed
      regarding public cell phone use.

PMID- 30105280
TI  - Dataset for electronic payment performance in Nigerian banking system: A trend
      analysis from 2012 to 2017.
AB  - The advent of Information and Communications Technology (ICT) in the new age has
      led to the digitalization of business processes including banking. For
      performance measurement among other usefulness, the dataset for these adopted
      electronic banking channels - Automated Teller Machines, Internet (Web)
      Transactions, Mobile Payments, Instant Payments, Electronic Fund Transfer, Point
      of Sales (POS), Automated Cheque Clearing and e-BillsPay was sourced. This
      dataset gives a trend analysis of e-payment performance of transactions both in
      value and volumes on each channel as consummated on the platform of Nigeria Inter
      Bank Settlement System (NIBSS) in the last six years covering 2012-2017.

PMID- 30105281
TI  - Iron Inhibits the Secretion of Apolipoprotein E in Cultured Human Adipocytes.

PMID- 30105283
TI  - Beyond Kras: MYC Rules in Pancreatic Cancer.

PMID- 30105282
TI  - A Method for Cryogenic Preservation of Human Biopsy Specimens and Subsequent
      Organoid Culture.

PMID- 30105284
TI  - Desmosome Disruption by Enteropathogenic E coli.

PMID- 30105285
TI  - The Age of Angiogenesis: A Novel Role of NGF in Gastric Repair.

PMID- 30105287
TI  - Walkable neighborhoods and obesity: Evaluating effects with a propensity score
      approach.
AB  - Background: Research investigating the connection between neighborhood
      walkability and obesity often overlooks the issue of nonrandom residential
      selection. Methods: We use propensity score methods to adjust for the nonrandom
      selection into residential neighborhoods in this cross-sectional, observational
      study. The sample includes 103,912 women residing in Salt Lake County, Utah age
      20 or older. We measured percentage living in neighborhoods with more
      walkability, area level measures of neighborhood characteristics, and obesity
      (body mass index (BMI) > 30). Results: Our findings confirm previous work that
      observes an association between living in more walkable neighborhoods and lower
      obesity. After adjusting for nonrandom selection, the odds of being obese when
      living in a less walkable neighborhood increase. Specifically, the odds ratio for
      being obese without the propensity score correction is 1.12. After adjusting for
      nonrandom selection, the odds ratio for being obese is 1.19, an increase of six
      percent. Conclusion: Results demonstrate that residential selection bias inherent
      in cross-sectional analysis slightly attenuates the true association between
      neighborhood walkability and obesity. Results lend support to the growing body of
      research suggesting that more walkable neighborhoods have residents with a lower
      prevalence of obesity. Absent propensity score controls, the causal relationship
      between environment and obesity would be underestimated by 6%. Our analysis
      suggests there is an association between neighborhood walkability and obesity.

PMID- 30105288
TI  - Optimal timing for precutting in cases with difficult biliary cannulation.
AB  - Background and study aims:  In endoscopic retrograde cholangiopancreatography
      (ERCP), precutting is widely used when achieving biliary cannulation is
      difficult. However, no consensus has been reached with regard to the best time to
      initiate precutting. Patients and methods:  We retrospectively examined 63
      patients who underwent precutting for naive papilla with difficulty in biliary
      cannulation between 2009 and 2016. The outcomes of the early precut group (<= 20
      min from cannulation until initiating precutting) and the late precut group (> 20
      min) were compared. Results:  Of the 63 patients, 17 (27 %) were in the early
      precut group and 46 (73 %) were in the late precut group; median time until the
      initiating precutting was 28 minutes (7 - 50). No significant difference was
      observed between the two groups in terms of clinical features (age, sex, and
      indication for ERCP), precutting method, and rate of pancreatic duct stent
      placement. Significantly higher rates of successful biliary cannulation were
      observed in the early precut group (16/17; 94 %) than in the late precut group
      (32/46; 70 %) ( P  < 0.05). In 13 patients in whom precutting was commenced after
      40 minutes, the rate of successful biliary cannulation was very low at 53 %
      (7/13). No significant difference was found between the two groups in terms of
      incidence of complications (pancreatitis in 5 patients and bleeding in 1
      patient). Conclusion:  In actual clinical practice, precutting is commenced
      approximately 30 minutes after cannulation; however, to successfully achieve
      biliary cannulation, precutting is recommended to be performed within 20 minutes.
      Precutting is effective when little inflammation and swelling of the ampulla of
      Vater is observed. This study was limited in that it was single-center,
      retrospective and had a small subject sample.

PMID- 30105289
TI  - Effectiveness of a modified 6-Fr endoscopic nasobiliary drainage catheter for
      patients with preoperative perihilar cholangiocarcinoma.
AB  - Background and study aims : To decrease complications associated with
      preoperative endoscopic nasobiliary drainage (ENBD) for perihilar
      cholangiocarcinoma patients, we developed a modified 6-Fr ENBD catheter with
      multiple side holes (m-ENBD). The aim of this retrospective study was to compare
      the m-ENBD catheter with a conventional 7-Fr ENBD catheter (c-ENBD). Patients and
      methods : This study involved 371 patients with suspected perihilar
      cholangiocarcinoma who underwent ENBD using a c-ENBD catheter or an m-ENBD
      catheter. The effectiveness of each catheter and the incidence of complications
      were evaluated. Univariate and multivariate analyses followed by propensity score
      matching were performed. Results : In 145 patients with total bilirubin levels >=
      2.0 mg/dL prior to drainage, these levels decreased to < 2.0 mg/dL after ENBD in
      81.1 % of the c-ENBD patients and in 74.0 % of the m-ENBD patients ( P  = 0.325).
      Post-ENBD cholangitis occurred in 24.9 % of the c-ENBD patients and in 12.4 % of
      the m-ENBD patients ( P  = 0.006). After propensity score matching, the rate of
      post-ENBD cholangitis ( P  = 0.007) and the number of patients requiring
      subsequent or additional drainage ( P  = 0.030) were significantly lower in the m
      ENBD group. Conclusion : The modified 6-Fr ENBD catheter was associated with a
      lower incidence of post-ENBD cholangitis than the conventional 7-Fr ENBD
      catheter, and the incidence of subsequent or additional drainage procedures was
      also decreased.

PMID- 30105286
TI  - Toll-Like Receptor-Mediated Intestinal Inflammatory Imbalance in the Pathogenesis
      of Necrotizing Enterocolitis.
AB  - Necrotizing enterocolitis (NEC) remains the leading cause of death from
      gastrointestinal disease in premature infants and attacks the most fragile
      patients at a time when they appear to be the most stable. Despite significant
      advances in our overall care of the premature infant, NEC mortality remains
      stubbornly high. There is no specific treatment for NEC beyond broad-spectrum
      antibiotics and intestinal resection, and current efforts have focused on
      preventive strategies. Over the past decade, we have proposed a unifying
      hypothesis to explain the pathogenesis of NEC in premature infants that suggests
      that NEC develops in response to an imbalance between exaggerated proinflammatory
      signaling in the mucosa of the premature gut leading to mucosal injury, which is
      not countered effectively by endogenous repair processes, and in the setting of
      impaired mesenteric perfusion leads to intestinal ischemia and disease
      development. One of the most important pathways that mediates the balance between
      injury and repair in the premature intestine, and that plays a key role in NEC
      pathogenesis, is Toll-like receptor 4 (TLR4), which recognizes lipopolysaccharide
      on gram-negative bacteria. This review focuses on the role that the TLR4-mediated
      imbalance between proinflammatory and anti-inflammatory signaling in the
      premature intestinal epithelium leads to the development of NEC, and will explore
      how an understanding of the role of TLR4 in NEC pathogenesis has led to the
      identification of novel preventive or treatment approaches for this devastating
      disease.

PMID- 30105292
TI  - Assessment of bowel cleansing quality in colon capsule endoscopy using machine
      learning: a pilot study.
AB  - Background and study aims:  The aim of this study was to develop a machine
      learning-based model to classify bowel cleansing quality and to test this model
      in comparison to a pixel analysis model and assessments by four colon capsule
      endoscopy (CCE) readers. Methods:  A pixel analysis and a machine learning-based
      model with four cleanliness classes (unacceptable, poor, fair and good) were
      developed to classify CCE videos. Cleansing assessments by four CCE readers in 41
      videos from a previous study were compared to the results both models yielded in
      this pilot study. Results:  The machine learning-based model classified 47 % of
      the videos in agreement with the averaged classification by CCE readers, as
      compared to 32 % by the pixel analysis model. A difference of more than one class
      was detected in 12 % of the videos by the machine learning-based model and in 32
      % by the pixel analysis model, as the latter tended to overestimate cleansing
      quality. A specific analysis of unacceptable videos found that the pixel analysis
      model classified almost all of them as fair or good, whereas the machine learning
      based model identified five out of 11 videos in agreement with at least one CCE
      reader as unacceptable. Conclusions:  The machine learning-based model was
      superior to the pixel analysis in classifying bowel cleansing quality, due to a
      higher sensitivity to unacceptable and poor cleansing quality. The machine
      learning-based model can be further improved by coming to a consensus on how to
      classify cleanliness of a complete CCE video, by means of an expert panel.

PMID- 30105291
TI  - Role of video capsule endoscopy in patients with constitutional mismatch repair
      deficiency (CMMRD) syndrome: report from the International CMMRD Consortium.
AB  - Background and study aims : Constitutional mismatch repair deficiency (CMMRD)
      syndrome, also known as biallelic mismatch repair deficiency (BMMRD) syndrome is
      a rare autosomal-recessive genetic disorder that has a high mortality due to
      malignancy in childhood and early adulthood. The small bowel phenotype in CMMRD
      is not well described and surveillance protocols for small bowel cancer have not
      been well established. This study was conducted to evaluate the usefulness and
      clinical impact of video capsule endoscopy (VCE) for small bowel surveillance.
      Patients and methods : We retrospectively reviewed the prospectively maintained
      International CMMRD Consortium database. Treating physicians were contacted and
      VCE report data were extracted using a standardized template. Results : Among 58
      patients included in the database, 38 VCE reports were collected from 17
      patients. Polypoid lesions were first detected on VCE at a median age of 14 years
      (range: 4 - 17). Of these, 39 % in 7 patients (15/38) showed large polypoid
      lesions (> 10 mm) or multiple polyps that prompted further investigations.
      Consequently, three patients were diagnosed with small bowel neoplasia including
      one patient with adenocarcinoma. Small bowel neoplasia and/or cancer were
      confirmed histologically in 35 % of the patients (6/17) who had capsule
      surveillance and the lesions in half of these patients were initially visualized
      on VCE. Multiple polyps were identified on eight VCEs that were completed on
      three patients. Ten VCEs (28 %) were incomplete due to slow bowel transit; none
      required capsule removal. Conclusions : Small bowel surveillance in patients with
      CMMRD should be initiated early in life. VCE has the potential to detect polyps;
      however, small bowel neoplasias are often proximal and can be missed, emphasizing
      the importance of concurrent surveillance with other modalities. Meeting
      presentations:  Digestive Disease Week 2017 and World Congress of Pediatric
      Gastroenterology, Hepatology and Nutrition 2016.

PMID- 30105290
TI  - Peroral endoscopic myotomy is effective and safe in non-achalasia esophageal
      motility disorders: an international multicenter study.
AB  - Background and study aims : The efficacy of per oral endoscopic myotomy (POEM) in
      non-achalasia esophageal motility disorders such as esophagogastric junction
      outflow obstruction (EGJOO), diffuse esophageal spasm (DES), and jackhammer
      esophagus (JE) has not been well demonstrated. The aim of this international
      multicenter study was to assess clinical outcomes of POEM in patients with non
      achalasia disorders, namely DES, JE, and EGJOO, in a large cohort of patients.
      Patients and methods : This was a retrospective study at 11 centers. Consecutive
      patients who underwent POEM for EGJOO, DES, or JE between 1/2014 and 9/2016 were
      included. Rates of technical success (completion of myotomy), clinical response
      (symptom improvement/Eckardt score <= 3), and adverse events (AEs, severity per
      ASGE lexicon) were ascertained . Results : Fifty patients (56 % female; mean age
      61.7 years) underwent POEM for EGJOO (n = 15), DES (n = 17), and JE (n = 18). The
      majority of patients (68 %) were treatment-naive. Technical success was achieved
      in all patients with a mean procedural time of 88.4 +/- 44.7 min. Mean total
      myotomy length was 15.1 +/- 4.7 cm. Chest pain improved in 88.9 % of EGJOO and
      87.0 % of DES/JE ( P  = 0.88). Clinical success was achieved in 93.3 % of EGJOO
      and in 84.9 % of DES/JE ( P  = 0.41) with a median follow-up of 195 and 272 days,
      respectively. Mean Eckardt score decreased from 6.2 to 1.0 in EGJOO ( P  < 0.001)
      and from 6.9 to 1.9 in DES/JE ( P  < 0.001). A total of 9 (18 %) AEs occurred and
      were rated as mild in 55.6 % and moderate in 44.4 %. Conclusion : POEM is
      effective and safe in management of non-achalasia esophageal motility disorders,
      which include DES, JE, and EGJOO.

PMID- 30105293
TI  - Post-polypectomy surveillance interval based on flexible spectral color imaging
      enhancement (FICE) with magnifying zoom imaging for optical biopsy.

PMID- 30105294
TI  - Two-year retrospective analysis of patients undergoing direct to procedure
      flexible sigmoidoscopy investigation with rectal bleeding as a primary complaint.
AB  - Background and aims:  Rectal bleeding affects ~15 % of the general population and
      is a common reason for referral to gastroenterologists by primary care
      physicians. Direct to procedure flexible sigmoidoscopy is an appealing modality
      to investigate rectal bleeding due its diagnostic yield, safety profile, and
      accessibility. Patients referred on a routine basis for direct to procedure
      clinic by primary care physicians with the sole complaint of rectal bleeding have
      not previously been studied. Our study aims to explore the spectrum of diagnoses
      and evaluate for potential clinical predictors of underlying pathology in this
      specific patient population. Methods:  In total, 528 charts of patients referred
      to the Kingston General Hospital and Hotel Dieu Hospital endoscopy units
      (Kingston, Canada) with the sole complaint of rectal bleeding were reviewed. All
      of these patients were referred on a routine basis to direct to procedure clinic
      from primary care physicians. The performance of various clinical variables in
      predicting significant pathology was assessed by univariate analysis. Results: 
      The diagnostic spectrum of the cohort studied included hemorrhoids (75.5 %), anal
      fissures (4 %), ulcerative colitis (3.2 %), Crohn's disease (1.1 %),
      indeterminate proctitis/colitis (1.7 %), and colorectal malignancy (2.7 %). Of
      the various clinical variables assessed, only male sex predicted significant
      pathology (25.2 % of males vs 17.6 % of females, P  < 0.05). Conclusion:  Our
      study highlights the need for a thorough investigation of rectal bleeding given
      the lack of clinical predictors. Future prospective studies with more patients
      are needed to fully assess the utility of various clinical variables in
      predicting pathology in this patient population. This would allow for more
      effective triaging of a routine rectal bleeding, a very common reason for patient
      referral to gastroenterologists by primary care physicians. Flexible
      sigmoidoscopy was not associated with complications or missed diagnosis in our
      study. As such, the technique appears to be a suitable initial investigative
      modality for patients with rectal bleeding.

PMID- 30105295
TI  - Global Evaluative Assessment of Robotic Skills in Endoscopy (GEARS-E): objective
      assessment tool for master and slave transluminal endoscopic robot.
AB  - Background and study aims:  The Master and Slave Transluminal Endoscopic Robot
      (MASTER) is a novel robotic endosurgical system with two operating arms that
      offer multiple degrees of freedom. We developed a new assessment tool, the Global
      Evaluative Assessment of Robotic Skills in Endoscopy (GEARS-E), derived from
      existing tools in laparoscopic and robotic surgery, and evaluated its utility in
      the performance of procedures using MASTER. Methods : This was a pilot study
      conducted in vivo and ex vivo on animals. Three operators (Novice-1, Novice-2 and
      Expert) performed a total of five endoscopic submucosal dissections (ESD) using
      MASTER. Novice operators had no MASTER experience and the expert had previously
      performed eight MASTER ESDs. Operator performance was assessed by four
      independent evaluators using GEARS-E, which has a maximum score of 25 for five
      domains representing various skill-related variables (depth perception, bimanual
      dexterity, efficiency, tissue handling and autonomy). Results : The mean global
      rating scores for Novice-1 first attempt, Novice-1 second attempt, Novice-2 first
      attempt, Novice-2 second attempt and Expert's cases were 13.0, 16.0, 13.3, 15.5,
      and 21.5, respectively. The mean scores of each of the five domains were
      statistically higher for the second attempts compared to the first attempts for
      both Novice-1 and Novice-2. The mean scores of each of the five domains for the
      Expert's case were consistently higher than those for the two novice operators in
      both their first and second attempts. Conclusion : Results using GEARS-E showed
      correlations between surgical experience and MASTER ESD. As an assessment tool
      for evaluation of surgical skills, GEARS-E has great potential for application in
      MASTER procedures.

PMID- 30105296
TI  - Feasibility of endoscopic mucosa-submucosa clip closure method (with video).

PMID- 30105297
TI  - Increased Axonal Bouton Stability during Learning in the Mouse Model of MECP2
      Duplication Syndrome.
AB  - MECP2 duplication syndrome is an X-linked form of syndromic autism caused by
      genomic duplication of the region encoding methyl-CpG-binding protein 2 (MECP2).
      Mice overexpressing MECP2 demonstrate social impairment, behavioral
      inflexibility, and altered patterns of learning and memory. Previous work showed
      abnormally increased stability of dendritic spines formed during motor training
      in the apical tuft of primary motor cortex (area M1) corticospinal neurons in the
      MECP2 duplication mouse model. In the current study, we measure the structural
      plasticity of axonal boutons in layer 5 pyramidal neuron projections to layer 1
      of area M1 during motor training. In wild-type littermate control mice, we find
      that during rotarod training the bouton formation rate changes minimally, if at
      all, while the bouton elimination rate more than doubles. Notably, the observed
      upregulation in bouton elimination with training is absent in MECP2 duplication
      mice. This result provides further evidence of an imbalance between structural
      stability and plasticity in this form of syndromic autism. Furthermore, the
      observation that axonal bouton elimination more than doubles with motor training
      in wild-type animals contrasts with the increase of dendritic spine consolidation
      observed in corticospinal neurons at the same layer. This dissociation suggests
      that different area M1 microcircuits may manifest different patterns of
      structural synaptic plasticity during motor training.

PMID- 30105298
TI  - Increasing Motor Noise Impairs Reinforcement Learning in Healthy Individuals.
AB  - Motor variability from exploration is crucial for reinforcement learning as it
      allows the nervous system to find new task solutions. However, motor variability
      from noise can be detrimental to learning and may underlie slowed reinforcement
      learning performance observed in individuals with cerebellar damage. Here we
      examine whether artificially increasing noise in healthy individuals slows
      reinforcement learning in a manner similar to that seen in patients with
      cerebellar damage. Participants used binary reinforcement to learn to rotate
      their reach angle in a series of directions. By comparing task performance
      between conditions with different levels of added noise, we show that adding a
      high level of noise-matched to a group of patients with cerebellar damage-slows
      learning. In additional experiments, we show that the detrimental effect of noise
      may lie in reinforcing incorrect behavior, rather than not reinforcing correct
      behavior. By comparing performance between healthy participants with added noise
      and a group of patients with cerebellar damage, we found that added noise does
      not slow the learning of the control group to the same degree observed in the
      patient group. Using a mechanistic model, we show that added noise in the present
      study matched patients' motor noise and total learning. However, increased
      exploration in the control group relative to the group with cerebellar damage
      supports faster learning. Our results suggest that motor noise slows
      reinforcement learning by impairing the mapping of reward to the correct action
      and that this may underlie deficits induced by cerebellar damage.

PMID- 30105299
TI  - Differentiation in Theta and Beta Electrocortical Activity between Visual and
      Physical Perturbations to Walking and Standing Balance.
AB  - Human balance is a complex process in healthy adults, requiring precisely timed
      coordination among sensory information, cognitive processing, and motor control.
      It has been difficult to quantify brain dynamics during human balance control due
      to limitations in brain-imaging modalities. The goal of this study was to
      determine whether by using high-density electroencephalography (EEG) and
      independent component analysis, we can identify common cortical responses to
      visual and physical balance perturbations during walking and standing. We studied
      the responses of 30 healthy young adults to sensorimotor perturbations that
      challenged their balance. Subjects performed four 10 min trials of beam walking
      and tandem stance while either being mediolaterally pulled at the waist or
      viewing brief 20 degrees  field-of-view rotations in virtual reality. We recorded
      high-density EEG, motion capture, lower leg electromyography (EMG), and neck EMG.
      We hypothesized that both physical pull and visual rotation perturbations would
      elicit time-frequency fluctuations in theta (4-8 Hz) and beta (13-30 Hz) bands,
      with increased occipito-parietal activity during visual rotations compared with
      pull perturbations. Our results confirmed this hypothesis. For both
      perturbations, we found early theta synchronization and late alpha-beta (8-30 Hz)
      desynchronization following perturbation onset. This pattern was strongest in
      occipito-parietal areas during visual perturbations and strongest in sensorimotor
      areas during pull perturbations. These results suggest a similar time-frequency
      electrocortical pattern when humans respond to sensorimotor conflict, but with
      substantive differences in the brain areas involved for visual versus physical
      perturbations. Our findings may have important implications for assessing and
      training balance in individuals with and without motor disabilities.

PMID- 30105300
TI  - Novel Quantitative Analyses of Spontaneous Synaptic Events in Cortical Pyramidal
      Cells Reveal Subtle Parvalbumin-Expressing Interneuron Dysfunction in a Knock-In
      Mouse Model of Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that has become a
      compelling global public health concern. Besides pathological hallmarks such as
      extracellular amyloid plaques, intracellular neurofibrillary tangles (NFTs), and
      loss of neurons and synapses, clinical reports have shown that epileptiform
      activity, even seizures, can occur early in the disease. Aberrant synaptic and
      network activities as well as epileptiform discharges have also been observed in
      various mouse models of AD. The new AppNL-F mouse model is generated by a gene
      knock-in approach and there are limited studies on basic synaptic properties in
      AppNL-F mice. Therefore, we applied quantitative methods to analyze spontaneous
      excitatory and inhibitory synaptic events in parietal cortex layer 2/3 pyramidal
      cells. First, by an objective amplitude distribution analysis, we found decreased
      amplitudes of spontaneous IPSCs (sIPSCs) in aged AppNL-F mice caused by a
      reduction in the amplitudes of the large sIPSCs with fast rates of rise,
      consistent with deficits in the function of parvalbumin-expressing interneurons
      (PV INs). Second, we calculated the burstiness and memory in a series of
      successive synaptic events. Lastly, by using a novel approach to determine the
      excitation-to-inhibition (E/I) ratio, we found no changes in the AppNL-F mice,
      indicating that homeostatic mechanisms may have maintained the overall balance of
      excitation and inhibition in spite of a mildly impaired PV IN function.

PMID- 30105302
TI  - Subsurface catalysis-mediated selectivity of dehydrogenation reaction.
AB  - Progress in heterogeneous catalysis is often hampered by the difficulties of
      constructing active architectures and understanding reaction mechanisms at the
      molecular level due to the structural complexity of practical catalysts, in
      particular for multicomponent catalysts. Although surface science experiments and
      theoretical simulations help understand the detailed reaction mechanisms over
      model systems, the direct study of the nature of nanoparticle catalysts remains a
      grand challenge. This paper describes a facile construction of well-defined Pt
      skin catalysts modified by different 3d transition metal (3dTM) atoms in
      subsurface regions. However, on the catalyst containing both surface and
      subsurface 3dTMs, the selectivity of propane dehydrogenation decreases in the
      sequences of Pt ~ PtFe > PtCo > PtNi due to the easier C-C cracking on exposed Co
      and Ni sites. After the exposed 3dTMs were removed completely, the C3H6
      selectivity was found to increase markedly in the row Pt < PtNi@Pt < PtCo@Pt <
      PtFe@Pt, which is in line with the calculated trend of d-band center shifting.
      The established relationship between reactivity and d-band center shifting
      illustrates the role of subsurface catalysis in dehydrogenation reaction.

PMID- 30105303
TI  - The optical duality of tellurium nanoparticles for broadband solar energy
      harvesting and efficient photothermal conversion.
AB  - Nanophotonic materials for solar energy harvesting and photothermal conversion
      are urgently needed to alleviate the global energy crisis. We demonstrate that a
      broadband absorber made of tellurium (Te) nanoparticles with a wide size
      distribution can absorb more than 85% solar radiation in the entire spectrum.
      Temperature of the absorber irradiated by sunlight can increase from 29 degrees 
      to 85 degrees C within 100 s. By dispersing Te nanoparticles into water, the
      water evaporation rate is improved by three times under solar radiation of 78.9
      mW/cm2. This photothermal conversion surpasses that of plasmonic or all
      dielectric nanoparticles reported before. We also establish that the unique
      permittivity of Te is responsible for the high performance. The real part of
      permittivity experiences a transition from negative to positive in the
      ultraviolet-visible-near-infrared region, which endows Te nanoparticles with the
      plasmonic-like and all-dielectric duality. The total absorption covers the entire
      spectrum of solar radiation due to the enhancement by both plasmonic-like and Mie
      type resonances. It is the first reported material that simultaneously has
      plasmonic-like and all-dielectric properties in the solar radiation region. These
      findings suggest that the Te nanoparticle can be expected to be an advanced
      photothermal conversion material for solar-enabled water evaporation.

PMID- 30105301
TI  - Sensory Adaptation to Chemical Cues by Vomeronasal Sensory Neurons.
AB  - Sensory adaptation is a source of experience-dependent feedback that impacts
      responses to environmental cues. In the mammalian main olfactory system (MOS),
      adaptation influences sensory coding at its earliest processing stages. Sensory
      adaptation in the accessory olfactory system (AOS) remains incompletely explored,
      leaving many aspects of the phenomenon unclear. We investigated sensory
      adaptation in vomeronasal sensory neurons (VSNs) using a combination of in situ
      Ca2+ imaging and electrophysiology. Parallel studies revealed prominent short
      term sensory adaptation in VSNs upon repeated stimulation with mouse urine and
      monomolecular bile acid ligands at interstimulus intervals (ISIs) less than 30 s.
      In such conditions, Ca2+ signals and spike rates were often reduced by more than
      50%, leading to dramatically reduced chemosensory sensitivity. Short-term
      adaptation was reversible over the course of minutes. Population Ca2+ imaging
      experiments revealed the presence of a slower form of VSN adaptation that
      accumulated over dozens of stimulus presentations delivered over tens of minutes.
      Most VSNs showed strong adaptation, but in a substantial VSN subpopulation
      adaptation was diminished or absent. Investigation of same- and opposite-sex
      urine responses in male and female VSNs revealed that adaptation to same-sex cues
      occurred at ISIs up to 180 s, conditions that did not induce adaptation to
      opposite-sex cues. This result suggests that VSN sensory adaptation can be
      modulated by sensory experience. These studies comprehensively establish the
      presence of VSN sensory adaptation and provide a foundation for future inquiries
      into the molecular and cellular mechanisms of this phenomenon and its impact on
      mammalian behavior.

PMID- 30105304
TI  - Current-induced dynamics of skyrmion strings.
AB  - Dynamics of string-like objects is an important issue in a broad range of
      physical systems, including vortex lines in superconductors, viscoelastic
      polymers, and superstrings in elementary particle physics. In noncentrosymmetric
      magnets, string forms of magnetic skyrmions are present as topological spin
      objects, and their current-induced dynamics has recently attracted intense
      interest. We show in the chiral magnet MnSi that the current-induced deformation
      dynamics of skyrmion strings results in transport response associated with the
      real-space Berry phase. Prominent nonlinear Hall signals emerge above the
      threshold current only in the skyrmion phase. We clarify the mechanism for these
      nonlinear Hall signals by adopting spin density wave picture to describe the
      moving skyrmion lattice; deformation of skyrmion strings occurs in an asymmetric
      manner due to the Dzyaloshinskii-Moriya interaction, which leads to the
      nonreciprocal nonlinear Hall response originating from an emergent
      electromagnetic field. This finding reveals the dynamical nature of string-like
      objects and consequent transport outcomes in noncentrosymmetric systems.

PMID- 30105306
TI  - Coherent perfect absorption of nonlinear matter waves.
AB  - Coherent perfect absorption is the complete extinction of incoming radiation by a
      complex potential in a physical system supporting wave propagation. The concept
      was proven for linear waves in a variety of systems including light interacting
      with absorbing scatterers, plasmonic metasurfaces, and graphene films, as well as
      sound waves. We extend the paradigm to coherent perfect absorption of nonlinear
      waves and experimentally demonstrate it for matter waves in an atomic Bose
      Einstein condensate. Coherent absorption of nonlinear matter waves is achieved
      easier than its linear analogs because the strength of two-body interactions
      offers additional freedom for control. Implementation of the coherent perfect
      absorber of Bose-Einstein condensates paves the way toward broad exploitation of
      the phenomenon in nonlinear optics, exciton-polariton condensates, acoustics, and
      other areas of nonlinear physics. It also opens perspectives for designing atom
      lasers.

PMID- 30105305
TI  - In situ manipulation and switching of dislocations in bilayer graphene.
AB  - Topological defects in crystalline solids are of fundamental interest in physics
      and materials science because they can radically alter the properties of
      virtually any material. Of particular importance are line defects, known as
      dislocations, which are the main carriers of plasticity and have a tremendous
      effect on electronic and optical properties. Understanding and controlling the
      occurrence and behavior of those defects have been of major and ongoing interest
      since their discovery in the 1930s. This interest was renewed with the advent of
      two-dimensional materials in which a single topological defect can alter the
      functionality of the whole system and even create new physical phenomena. We
      present an experimental approach to directly manipulate dislocations in situ on
      the nanometer scale by using a dedicated scanning electron microscope setup. With
      this approach, key fundamental characteristics such as line tension, defect
      interaction, and node formation have been studied. A novel switching reaction,
      based on the recombination of dislocation lines, was found, which paves the way
      for the concept of switches made of a bimodal topological defect configuration.

PMID- 30105307
TI  - Bioinspired polymeric woods.
AB  - Woods provide bioinspiration for engineering materials due to their superior
      mechanical performance. We demonstrate a novel strategy for large-scale
      fabrication of a family of bioinspired polymeric woods with similar polyphenol
      matrix materials, wood-like cellular microstructures, and outstanding
      comprehensive performance by a self-assembly and thermocuring process of
      traditional resins. In contrast to natural woods, polymeric woods demonstrate
      comparable mechanical properties (a compressive yield strength of up to 45 MPa),
      preferable corrosion resistance to acid with no decrease in mechanical
      properties, and much better thermal insulation (as low as ~21 mW m-1 K-1) and
      fire retardancy. These bioinspired polymeric woods even stand out from other
      engineering materials such as cellular ceramic materials and aerogel-like
      materials in terms of specific strength and thermal insulation properties. The
      present strategy provides a new possibility for mass production of a series of
      high-performance biomimetic engineering materials with hierarchical cellular
      microstructures and remarkable multifunctionality.

PMID- 30105308
TI  - Molecular catalyst systems as key enablers for tailored polyesters and
      polycarbonate recycling concepts.
AB  - A transition metal catalyst system for the selective catalytic depolymerization
      of various polyester- and polycarbonate-based materials is presented. The use of
      a molecular ruthenium catalyst with selected triphos ligands enabled a selective
      hydrogenolysis of a large diversity of polymeric consumer products, paving the
      way to innovative and sustainable recycling strategies within a circular economy.

PMID- 30105309
TI  - Podocalyxin is crucial for the growth of oral squamous cell carcinoma cell line
      HSC-2.
AB  - Oral cancers constitute approximately 2% of all cancers, with the most common
      histological type being oral squamous cell carcinoma (OSCC), representing 90% of
      oral cancers. Although diagnostic technologies and therapeutic techniques have
      progressed, the survival rate of patients with OSCC is still 60%, whereas the
      incidence rate has increased. Podocalyxin (PODXL) is a highly glycosylated type I
      transmembrane protein that is detected in normal tissues such as heart, breast,
      and pancreas as well as in many cancers, including lung, renal, breast,
      colorectal, and oral cancers. This glycoprotein is associated with the
      progression, metastasis, and poor outcomes of oral cancers. PODXL overexpression
      was strongly detected using our previously established anti-PODXL monoclonal
      antibody (mAb), PcMab-47, and its mouse IgG2a-type, 47-mG2a. In previous studies,
      we also generated PODXL-knock out (PODXL-KO) cell lines using SAS OSCC cell
      lines, in order to investigate the function of PODXL in the proliferation of oral
      cancer cells. The growth of SAS/PODXL-KO cell lines was observed to be lower than
      that of parental SAS cells. For this study, PODXL-KO OSCC cell lines were
      generated using HSC-2 cells, and the role of PODXL in the growth of OSCC cell
      lines in vitro was assessed. Decreased growth was observed for HSC-2/PODXL-KO
      cells compared with HSC-2 parental cells. The influence of PODXL on tumor growth
      of OSCC was also investigated in vivo, and both the tumor volume and the tumor
      weight were observed to be significantly lower for HSC-2/PODXL-KO than that for
      HSC-2 parental cells. These results, taken together, indicate that PODXL plays an
      important role in tumor growth, both in vitro and in vivo.

PMID- 30105310
TI  - A systematic review and meta-analysis of prevalence of Escherichia coli in foods
      of animal origin in Ethiopia.
AB  - Escherichia coli is one of the causes of gastrointestinal diseases worldwide
      causing millions of illness annually. The occurrence of Escherichia coli in foods
      of animal origin in Ethiopia is arguably high due to many reasons like illegal
      slaughtering of animals in open fields, unhygienic slaughter practices in the
      abattoirs, and the risk of disease due to this organism is high because of a
      widespread tradition of raw meat consumption. The objective of this systematic
      review and meta-analysis was to pool estimates of the prevalence of the organism
      in different foods of animal origin which is the first of its kind in the
      country. The literature search was conducted to identify all published articles
      reporting the prevalence of Escherichia coli in foods of animal origin. From all
      screened articles, 30 studies were eligible for final systematic review and meta
      analysis. Because substantial heterogeneity was expected, random-effects meta
      analyses were carried out to pool the prevalence of the organism from different
      foods of animal origin. The result indicated that between-study variability was
      high (tau2 = 0.00; heterogeneity I2 = 96.77% with Heterogeneity chi-square =
      1298.92, a degree of freedom = 42 and a P-value of = 0.001) with the overall
      random pooled prevalence of 15% (95% CI = 13%-17%) in foods of animal origin. The
      result of meta-regression showed diagnosis method used, sample size and study
      year had contributed significantly to the heterogeneity of studies. This
      systematic review and meta-analysis showed the level of contamination of foods of
      animal origin in Ethiopia is high indicating the need for immediate planning of
      mitigation strategies and detection methods to reduce its level and impact
      throughout the country.

PMID- 30105311
TI  - Effect of the LEGe detector collimators on K-series peaks and Compton scattering
      in XRF analysis using gamma rays.
AB  - The effect of a low-energy germanium detector collimator with different diameters
      on the measurement of the X-ray fluorescence of palladium (Pd) was studied
      experimentally. Changes in the Pd K-series and Compton scattering peaks were
      measured and analysed with and without a detector collimator, where for the
      former, collimators with different diameters were used. The signal-to-noise ratio
      increased when a shielding collimator was used with a narrow detector collimator.
      The Compton dispersion and fraction dead time were reduced considerably using a
      detector collimator by increasing the distance from the source to the detector,
      and the collimator length-to-diameter ratio. The full width at half maximum
      (FWHM) of the Pd Kalpha1 and Pd Kbeta1 peaks decreased almost linearly with the
      collimator length-to-diameter ratio. The FWHM illustrated that the spectral
      resolution was improved when a collimator with a smaller diameter but unchanged
      length was used. The uncertainties at the Pd Kalpha1, Pd Kbeta1, and Compton
      dispersion peaks were approximately correlated linearly with the collimator
      length-to-diameter ratio.

PMID- 30105312
TI  - Macular ganglion cells alteration in a patient with left homonymous hemianopia
      subsequent to surgical excision of an arteriovenous malformation.
AB  - Purpose: To report the case of a 57 years old woman who showed a macular ganglion
      cell complex (GCC), that is a combination of ganglion cell layer and inner
      plexiform layer, and peripapillary Retinal Nerve Fiber Layer (pRNFL) thickness
      reduction in association with left homonymous hemianopia subsequent to surgical
      excision of an arteriovenous malformation in the cerebral right occipital lobe 37
      years before. Observations: One patient with left homonymous hemianopia due to
      surgical excision of an arteriovenous malformation in the right cerebral
      occipital lobe came to our attention for transient blurred vision.Measurement of
      the GCC and pRNFL thickness was performed using spectral domain optical coherence
      tomography (SDOCT; Cirrus HD-OCT model 400). Visual field (VF) defects were
      assessed using Humphrey field analyzer using the central 30-2 Swedish Interactive
      Threshold Algorithm (SITA) program with appropriate trial lenses (Humphrey Field
      Analyzer II, Carl Zeiss Meditech, Inc, Dublin, California).The average pRNFL
      thickness was bilaterally reduced, showing a symmetry value of 39%. The patients
      showed a significant GCC thinning in the projecting sector of the retina mapping
      to the brain lesion. Corresponding VF defects were found. Conclusions and
      importance: These findings show SDOCT potentials in the field of neuro
      ophthalmology, supporting the usefulness of GCC thickness as a possible imaging
      marker before and after brain surgery, and, possibly, in the diagnosis of
      neurodegenerative conditions.

PMID- 30105313
TI  - OXIDATIVE STRESS IN REPRODUCTIVE TOXICOLOGY.
AB  - Oxidative stress (OS) has been implicated in the causation of environmentally
      induced diseases. However, the role of toxicants in the pathophysiology of
      disorders and diseases affecting the reproductive system are less understood.
      This review focuses on some of the mechanisms that underlie OS-induced
      reproductive toxicity at the cellular- and organ levels (germ cell damage and
      perturbed organ responses to endocrine stimuli). While most of the reproductive
      and developmental studies conducted in adult animals and transgenerational adult
      animals point to the involvement of genotoxicity, the part played by epigenetic
      alterations is accorded a recent recognition, thus warranting more studies in
      this area. Additionally, metabolomic, proteomic and transcriptomic approaches
      need to be employed to advance our understanding of key metabolites formed and
      the expression of anti-OS genes at the molecular level that are necessary for
      combating reactive oxygen species formation. The resulting data could be analyzed
      using bioinformatics tools to identify the pathways linked to disease causation
      and as a consequence, the adoption of therapeutic strategies, including but not
      limited to administering phytochemicals (many of which possess antioxidant
      properties) to improve disease outcomes.

PMID- 30105315
TI  - Supramolecular nanopatterns of H-shaped molecules.
AB  - Alkoxy-substituted phenylene-ethynylene-butadiynylenes (PEBs) are connected via
      1H-benzimidazole units to form H-shaped molecular scaffolds that self-assemble on
      graphite at the solid/liquid interface. Spacer lengths and end groups determine
      supramolecular tiling patterns, as shown via scanning tunneling microscopy (STM).

PMID- 30105316
TI  - Silicoaluminophosphate-11 (SAPO-11) molecular sieves synthesized via a grinding
      synthesis method.
AB  - Aluminophosphate molecular sieves with an AEL-type structure and various
      framework compositions were prepared via a grinding synthesis method (GSM). The
      rapid crystal growth rate was due to the enhanced interactions between the
      templates and aluminum species and abundant low-polymerized phosphorus species.
      The amount of template and water used was substantially reduced, which has a
      great economic and environment impact for large-scale synthesis.

PMID- 30105317
TI  - Compressing liquid nanofoam systems: liquid infiltration or nanopore deformation?
AB  - Understanding the invasion of a liquid into porous structures is the foundation
      of the characterization of the porosity-related properties of materials and is
      also of fundamental importance in the design of porous solid-liquid enabled
      energy protection systems, yet whether solid pores deform has been unclear so
      far. Here, we present a competition mechanism between liquid infiltration and
      cell wall buckling deformation by investigating a liquid nanofoam (LN) system
      subjected to quasi-static compression. The critical buckling stress of the cell
      wall and the infiltration pressure of liquid invasion into nanopores are studied
      and correlated through numerical simulation and experimental validation to reveal
      the quantitative relationship between nanopore deformation and liquid invasion.
      The analysis shows that liquid infiltration occurs, independent of the axial
      buckling stress of the cell wall; in contrast, the nanopore collapses radially
      when the radial collapse pressure is lower than the pressure of liquid
      infiltration, preventing the liquid invasion. Comprehensive molecular dynamics
      (MD) simulations are performed and demonstrate the deformation behavior of
      nanopores and cell wall-liquid interactions in a broad range. Pressure-induced
      compression experiments on a silica-based LN system are carried out and validate
      these theoretical and MD results.

PMID- 30105314
TI  - Preserved cardiac function by vinculin enhances glucose oxidation and extends
      health- and life-span.
AB  - Despite limited regenerative capacity as we age, cardiomyocytes maintain their
      function in part through compensatory mechanisms, e.g., Vinculin reinforcement of
      intercalated discs in aged organisms. This mechanism, which is conserved from
      flies to non-human primates, creates a more crystalline sarcomere lattice that
      extends lifespan, but systemic connections between the cardiac sarcomere
      structure and lifespan extension are not apparent. Using the rapidly aging fly
      system, we found that cardiac-specific Vinculin-overexpression [Vinculin heart
      enhanced (VincHE)] increases heart contractility, maximal cardiac mitochondrial
      respiration, and organismal fitness with age. Systemic metabolism also
      dramatically changed with age and VincHE; steady state sugar concentrations, as
      well as aerobic glucose metabolism, increase in VincHE and suggest enhanced
      energy substrate utilization with increased cardiac performance. When cardiac
      stress was induced with the complex I inhibitor rotenone, VincHE hearts sustain
      contractions unlike controls. This work establishes a new link between the
      cardiac cytoskeleton and systemic glucose utilization and protects mitochondrial
      function from external stress.

PMID- 30105318
TI  - Determination of the protonation preferences of bilin pigments in cryptophyte
      antenna complexes.
AB  - The light-harvesting mechanisms of cryptophyte antenna complexes have attracted
      considerable attention due to their ability to exhibit maximal photosynthetic
      activity under very low-light conditions and to display several colors, as well
      as the observation of vibronic coherent features in their two-dimensional
      electronic spectra. However, detailed investigations on the interplay between the
      protein environment and their light-harvesting properties are hampered by the
      uncertainty related to the protonation state of the underlying bilin pigments.
      Here we study the protonation preferences of four types of bilin pigments
      including 15,16-dihydrobiliverdin (DBV), phycoerythrobilin (PEB), phycocyanobilin
      (PCB) and mesobiliverdin (MBV), which are found in phycoerythrin PE545 and
      phycocyanin PC577, PC612, PC630 and PC645 complexes. We apply quantum chemical
      calculations coupled to continuum solvation calculations to predict the intrinsic
      acidity of bilins in aqueous solution, and then combine molecular dynamics
      simulations with empirical pKa estimates to investigate the impact of the local
      protein environment on the acidity of the pigments. We also report measurements
      of the absorption spectra of the five complexes in a wide range of pH in order to
      validate our simulations and investigate possible changes in the light harvesting
      properties of the complexes in the range of physiological pH found in the lumen
      (pH ~ 5-7). The results suggest a pKa > 7 for DBV and MBV pigments in the alpha
      polypeptide chains of PE545 and PC630/PC645 complexes, which are not coordinated
      to a negatively charged amino acid. For the other PEB, DBV and PCB pigments,
      which interact with a Glu or Asp side chain, higher pKa values (pKa > 8) are
      estimated. Overall, the results support a preferential population of the fully
      protonated state for bilins in cryptophyte complexes under physiological
      conditions regardless of the specific type of pigment and local protein
      environment.

PMID- 30105319
TI  - Visible-light promoted fluoroalkylselenolation: toward the reactivity of
      unsaturated compounds.
AB  - The reactivity of fluoroalkylselenotoluenesulfonates with unsaturated substrates
      is explored herein. The direct activation of these shelf-stable reagents under
      visible light allows the double functionalisation of alkenes or alkynes
      efficiently, leading to a wide range of beta-fluoroalkylselenolated sulfones.
      Mechanistic investigations have been undertaken supporting the formation of
      radical intermediates.

PMID- 30105320
TI  - Simple method to construct three-dimensional porous carbon for electrochemical
      energy storage.
AB  - A 3D porous carbon matrix with a high nitrogen content has been synthesized by
      employing particles of a nitrogen-enriched superabsorbent polymer (SAP) from the
      waste diapers of newborn babies. The derived material exhibits an ultrathin
      layered structure with interconnected pores and a large specific surface area. As
      it inherits the unique skeleton of the functional polymer from waste diapers, the
      resulting material (NSAPC-W) has been assessed as an inserting host anode with
      excellent ultralong cycling performance, as well as steady rate capability for
      both Li+ and Na+ ions in half cells. Furthermore, the unique structure imparts
      intimate structural interconnectivity, wide open channels for ion diffusion, and
      a large accessible surface area, as well as high structural stability, and opens
      up a wide horizon for electrochemical applications.

PMID- 30105321
TI  - Multiplex sample-to-answer detection of bacteria using a pipette-actuated
      capillary array comb with integrated DNA extraction, isothermal amplification,
      and smartphone detection.
AB  - A pipette-actuated capillary array comb (PAAC) system operated on a smartphone
      based hand-held device has been successfully developed for the multiplex
      detection of bacteria in a "sample-to-answer" manner. The PAAC consists of eight
      open capillaries inserted into a cylindrical plastic base with a piece of
      chitosan-modified glass filter paper embedded in each capillary. During the
      sample preparation, a PAAC was mounted into a 1 mL pipette tip with an enlarged
      opening and was operated with a 1 mL pipette for liquid handling. The cell lysate
      was drawn and expelled through the capillaries three times to facilitate the DNA
      capture on the embedded filter discs. Following washes with water, the loop
      mediated isothermal amplification (LAMP) reagents were aspirated into the
      capillaries, in which the primers were pre-fixed with chitosan. After that, the
      PAAC was loaded into the smartphone-based device for a one-hour amplification at
      65  degrees C and end-point detection of calcein fluorescence in the capillaries.
      The DNA capture efficiency of a 1.1 mm-diameter filter disc was determined to be
      97% of lambda-DNA and the coefficient of variation among the eight capillaries in
      the PAAC was only 2.2%. The multiplex detection of genomic DNA extracted from
      Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus provided
      limits of detection of 200, 500, and 500 copies, respectively, without any cross
      contamination and cross reactions. "Sample-to-answer" detection of E. coli
      samples was successfully completed in 85 minutes, demonstrating a sensitivity of
      200 cfu per capillary. The multiplex "sample-to-answer" detection, the
      streamlined operation, and the compact device should facilitate a broad range of
      applications of our PAAC system in point-of-care testing.

PMID- 30105322
TI  - A hybrid hydrazine redox flow battery with a reversible electron acceptor.
AB  - Hydrazine is a pollutant with high hydrogen content, offering tremendous
      possibilities in a direct hydrazine fuel cell (DHFC) as it can be converted into
      electricity via benign end products. Due to the inner sphere nature of half-cell
      chemistries, hydrazine cross over triggers parasitic chemistry at the Pt-based
      air cathode of a state-of-the-art DHFC, overly complicating the already sluggish
      electrode kinetics at the positive electrode. Here, we illustrate that by
      altering the interfacial chemistry of the catholyte from inner sphere to outer
      sphere, the parasitic chemistry can be dissociated from the redox chemistry of
      the electron acceptor and the hybrid fuel cell can be driven by simple carbon
      based cathodes. The reversible nature of an outer sphere catholyte leads to a
      hybrid fuel cell redox flow battery with performance metrics ~4 times higher than
      a Pt-based DHFC-air configuration.

PMID- 30105323
TI  - On the exfoliation and anisotropic thermal expansion of black phosphorus.
AB  - Black phosphorus is a bulk solid allotrope of elemental phosphorus and can be
      seen as an infinite stack of phosphorene sheets. It is interesting from a
      technological point of view as well as from an electronic structure perspective
      due to the importance of electron correlation effects. In a recent paper [M.
      Schutz, L. Maschio, A. J. Karttunen and D. Usvyat, J. Phys. Chem. Lett., 2017, 8,
      1290-1294] a highly accurate exfoliation energy has been computed. Building upon
      these results we carefully benchmark various dispersion-corrected density
      functional approximations. The choice of the range-separating function that
      suppresses London dispersion at short interatomic distances apparently has a
      substantial influence on the results. Having chosen the suitable functional, we
      have computed the thermal expansion coefficients of black phosphorous via a quasi
      harmonic approximation. The computed coefficients manifest a strong anisotropy
      between the two in-plane directions. Our calculations, however, do not support
      the existence of negative thermal expansion in black phosphorus, as reported in
      some theoretical studies.

PMID- 30105324
TI  - Ultra-low power Hf0.5Zr0.5O2 based ferroelectric tunnel junction synapses for
      hardware neural network applications.
AB  - Brain-inspired neuromorphic computing has shown great promise beyond the
      conventional Boolean logic. Nanoscale electronic synapses, which have stringent
      demands for integration density, dynamic range, energy consumption, etc., are key
      computational elements of the brain-inspired neuromorphic system. Ferroelectric
      tunneling junctions have been shown to be ideal candidates to realize the
      functions of electronic synapses due to their ultra-low energy consumption and
      the nature of ferroelectric tunneling. Here, we report a new electronic synapse
      based on a three-dimensional vertical Hf0.5Zr0.5O2-based ferroelectric tunneling
      junction that meets the full functions of biological synapses. The fabricated
      three-dimensional vertical ferroelectric tunneling junction synapse (FTJS)
      exhibits high integration density and excellent performances, such as analog-like
      conductance transition under a training scheme, low energy consumption of
      synaptic weight update (1.8 pJ per spike) and good repeatability (>103 cycles).
      In addition, the implementation of pattern training in hardware with strong
      tolerance to input faults and variations is also illustrated in the 3D vertical
      FTJS array. Furthermore, pattern classification and recognition are achieved, and
      these results demonstrate that the Hf0.5Zr0.5O2-based FTJS has high potential to
      be an ideal electronic component for neuromorphic system applications.

PMID- 30105326
TI  - Arsagermene, a compound with an -As[double bond, length as m-dash]Ge[double bond
      splayed right] double bond.
AB  - The first compound featuring an As[double bond, length as m-dash]Ge double bond,
      arsagermene Mes*As[double bond, length as m-dash]Ge(SiMetBu2)2, was synthesized,
      isolated and fully characterized. Crystallographic studies revealed that
      arsagermene has a planar Ge[double bond, length as m-dash]As bond of 2.2731(8) A,
      which is notably shorter than the standard Ge-As single bond. The double bond
      character of arsagermene was further supported by computational data.

PMID- 30105327
TI  - De novo design of small molecule acceptors via fullerene/non-fullerene hybrids
      for polymer solar cells.
AB  - Two fullerene/non-fullerene hybrids were designed and synthesized for polymer
      solar cells as small molecule acceptors. Polymer solar cells based on J71:A2
      achieved a power conversion efficiency of 4.52% with the open circuit voltage at
      nearly 1.0 V. The success of the hybrids may pave a new way for small molecule
      acceptors.

PMID- 30105328
TI  - Metal-organic framework-templated synthesis of sulfur-doped core-sheath
      nanoarrays and nanoporous carbon for flexible all-solid-state asymmetric
      supercapacitors.
AB  - Metal-organic frameworks (MOFs) provide great opportunities for synthesizing
      advanced electrode materials with hierarchical hollow architectures for energy
      storage. Herein, we report the facile fabrication of core-sheath nanoarrays (NAs)
      on carbon cloth (CC@CoO@S-Co3O4) for binder-free electrode materials with MOFs as
      versatile scaffolds. The hollow S-doped Co3O4 sheath has been facilely prepared
      using a two-step synthetic protocol, which includes the surface etching of CoO
      nanowires for synchronous in situ growth of well-aligned ZIF-67 and its following
      hydrothermal process. The synergistic effect between CC nanofibers and hollow
      ordered NAs ensures efficient mass and electron transport. The pseudocapacitive
      NAs present a highest areal specific capacitance of 1013 mF cm-2 at 1 mA cm-2. By
      assembling the same MOF-derived nanoporous carbons and NAs as the corresponding
      binder-free anode and cathode, the flexible all-solid-state asymmetric
      supercapacitors deliver a highest energy density of 0.71 mW h cm-3 at 21.3 mW cm
      3 power density, together with 87.9% capacitance retention over 5000 continuous
      cycles.

PMID- 30105329
TI  - A semiconductor and fluorescence dual-mode room-temperature ammonia sensor
      achieved by decorating hydroquinone into a metal-organic framework.
AB  - Presented herein is a magnesium-organic framework (SNNU-88) incorporated with
      active hydroquinone groups, which exhibits not only remarkable semiconductor
      sensing for traces of ammonia vapor (5-100 ppm), but also extra-high fluorescence
      response to liquid NH3.H2O through an unusual turn-off (0-1.5 ppm) and turn-on
      (3.0-100 ppm) luminescence sensing mechanism at room temperature. Such
      bifunctional quantitative ammonia detection together with the extraordinary
      sensitivity and selectivity, fast response, and good reusability makes SNNU-88
      one of the most powerful ammonia sensors.

PMID- 30105331
TI  - Programmable microfluidic logic device fabricated with a shape memory polymer.
AB  - Manipulation of particles in a microfluidic system is an important research
      subject in biomedical engineering. However, most conventional passive techniques
      for particle control have difficulties in integrating other functions into
      microfluidic channels. A unique microfluidic valve was proposed in this study for
      switchable particle control by employing a shape memory polymer (SMP). A
      microfluidic logic device can be programmed based on deformation of the SMP
      microchannel constructed on a poly(dimethylsiloxane) (PDMS) film. Particles in a
      viscoelastic flow were focused at preferred equilibrium locations by the
      competition between inertia and elastic forces. The channel shape played an
      important role in determining those forces in the channel. Hydrodynamic behavior
      and shape recovery behavior of the SMP microchannel were modeled theoretically.
      It was confirmed that the particle valve prepared with the SMP implemented a
      programmable binary logic operation in the microfluidic channel.

PMID- 30105332
TI  - A recyclable hydroxyl functionalized polyindole hydrogel for sodium hydroxide
      extraction via the synergistic effect of cation-pi interactions and hydrogen
      bonding.
AB  - We have successfully constructed a new type of recyclable indole-based hydrogel,
      which exhibited highly effective extraction behavior for hydroxide via the
      synergistic effect of cation-pi interactions and hydrogen bonds. More
      interestingly, the absorption performance could be visually detected by taking
      advantage of the color altering effect of the host-guest interactions.

PMID- 30105333
TI  - Femtosecond infrared spectroscopy reveals the primary events of the ferrioxalate
      actinometer.
AB  - Chemical actinometry is an indispensable analytical tool in preparative
      photochemistry that allows for a precise measurement of radiant fluxes inside
      photoreactors. An actinometer thus enables an absolute determination of the
      quantum yield of a photochemical reaction of interest. The "gold standard" of
      chemical actinometry in liquid systems is the Hatchard-Parker actinometer, i.e.
      an aqueous solution of potassium trisoxalatoferrate(iii), which is based on the
      light-induced net transformation of ferric into ferrous oxalate complexes.
      Although the absolute photochemical quantum yield for this fundamental standard
      system has been accurately known for many years, the underlying molecular-level
      mechanisms and time scales associated with a photoreduction of the ferrioxalate
      actinometer remained so far largely obscured. Here, we use femtosecond mid
      infrared spectroscopy combined with ultrafast laser photolysis to obtain unique
      structural-dynamical information associated with the primary light-triggered
      processes thereby finally providing the missing quantitative molecular-level
      foundations that ultimately justify a utilization of aqueous ferrioxalate as a
      true photochemical standard. Following photon absorption by the octahedral parent
      complex, an ultrafast decarboxylation occurs within 500 fs, which generates a
      penta-coordinated ferrous dioxalate that carries a bent carbon dioxide radical
      anion ligand in an "end-on" O-coordinated fashion. This unique intermediate
      structurally isomerizes on a tens of picoseconds time scale and subsequently
      loses a CO2--ligand to form a square-planar bisoxalatoferrate(ii) on a hundreds
      of picoseconds time scale.

PMID- 30105334
TI  - A computational study of the vibrationally-resolved electronic circular dichroism
      spectra of single-chain transoid and cisoid oligothiophenes in chiral
      conformations.
AB  - We simulate the vibronic profile of the electronic circular dichroism (ECD)
      spectra of oligothiophenes in cisoid and transoid chiral arrangements. We
      consider oligomers of different lengths, from two to fifteen units, and
      investigate extensively how the ECD spectral shapes depend on the inter-ring
      torsions. In general, the molecular structures we consider are not stationary
      points of the ground state potential energy surface. Therefore, in order to
      perform vibronic calculations, we present a new computational protocol able to
      define reduced-dimensionality models where the effect of the off-equilibrium
      modes is removed. This is done adopting a description of the vibrational motions
      in curvilinear internal coordinates, and vertical harmonic models coupled with an
      iterative application of projectors to define energy Hessians, and therefore
      effective normal modes, in the space complementary to the one of the off
      equilibrium coordinates. Although we consider both Franck-Condon and Herzberg
      Teller contributions, the results show that transoid twisted ribbons always give
      rise to monosignated ECD spectra, while bi-signated and multi-signated spectra
      are expected for cisoid helices. These findings are explained on the basis of the
      different transition strengths of the lowest electronic states imparted by the
      different spatial arrangement, that is almost linear for transoid structures and
      more globular for cisoid ones. We predicted the chiroptical response of a large
      number of possible molecular arrangements. These data are employed to critically
      discuss the experimental ECD of polythiophenes in different experimental
      conditions, forming either aggregates or host-guest complexes. The method here
      proposed to perform vibronic calculations in reduced-dimensionality models is of
      general applicability and its potential interest goes beyond the practical
      application presented here.

PMID- 30105335
TI  - A smartphone-based quantitative detection platform of mycotoxins based on
      multiple-color upconversion nanoparticles.
AB  - The detection of mycotoxins in food is urgently needed because they pose a
      significant threat to public health. In this study, we developed a quantitative
      detection platform for mycotoxins by integrating multicolor upconversion
      nanoparticle barcode technology with fluorescence image processing using a
      smartphone-based portable device. The multi-colored upconversion nanoparticle
      encoded microspheres (UCNMs) were used as encoded signals for detecting different
      mycotoxins simultaneously. After indirect competitive immunoassays using UCNMs,
      images could be captured by the portable device and the camera of a smartphone.
      Then, a self-written Android application, which is an HSV-based image recognition
      program installed on a smartphone, analyzed images and offered a reliable and
      accurate result in less than 1 min. The quantitative detection platform of
      mycotoxins proved to be feasible and reliable, and the limit of detection (LOD)
      was 1 ng, which was lower than that obtained from standard assays. This study
      demonstrates a method for detecting mycotoxins in food and other point of care
      analysis.

PMID- 30105336
TI  - Dissociative electron attachment to HGaF4 Lewis-Bronsted superacid.
AB  - The consequences of an excess electron attachment to HGaF4 (HF/GaF3) superacid
      are investigated on the basis of theoretical calculations employing ab initio
      methods. It is found that the dipole potential of HGaF4 plays an important role
      in the initial formation of a dipole-bound anionic state. Due to the kinetic
      instability of that initially formed anion, a fragmentation reaction occurs
      promptly and leads to (GaF4)- and H as the final products. The energy profile of
      this process, its rate, and mechanism are presented and discussed.

PMID- 30105337
TI  - New topological states in HgTe quantum wells from defect patterning.
AB  - To explore new methods for the realization of the quantum spin Hall (QSH) effect
      in two-dimensional (2D) materials, we have constructed a honeycomb geometry (HG)
      by etching rows of hexagonal holes in HgTe quantum wells (QWs). Theoretical
      calculations show that multiple Dirac cones can be produced by HG, regardless of
      whether the band inversion occurs or not. Furthermore, the topological states
      originating from a narrow HG region in a wide ribbon show strong localization at
      the physical edges of the ribbon, making them easy to manipulate and exploit.
      When the band inversion condition for QW states is satisfied, the topological
      states generated by two different mechanisms may coexist. Our studies pave the
      way to produce and control multiple QSH states in 2D materials as desired for the
      design of innovative spintronic materials.

PMID- 30105338
TI  - Fluorescence enhancement from single gold nanostars: towards ultra-bright
      emission in the first and second near-infrared biological windows.
AB  - Gold nanostars (AuNSs) are promising agents for the development of high
      performance diagnostic devices, by enabling metal enhanced fluorescence (MEF) in
      the physiological near-infrared (NIR) and second near-infrared (NIR-II) windows.
      The local electric field near their sharp tips and between their branches can be
      enhanced by several orders of magnitude, holding great promise for large
      fluorescence enhancements from single AuNS particles, rather than relying on
      interparticle coupling in nanoparticle substrates. Here, guided by electric field
      simulations, two different types of AuNSs with controlled morphologies and
      plasmonic responses in the NIR and NIR-II regions are used to investigate the
      mechanism of MEF from colloidal AuNSs. Fluorophore conjugation to AuNSs allows
      significant fluorescence enhancement of up to 30 times in the NIR window, and up
      to 4-fold enhancement in the NIR-II region. Together with other inherent
      advantages of AuNSs, including their multispike morphology offering easy access
      to cell membranes and their large surface area providing flexible
      multifunctionality, AuNS are promising for the development of in vivo imaging
      applications. Using time-resolved fluorescence measurements to deconvolute semi
      quantitatively excitation enhancement from emission enhancement, we show that a
      combination of enhanced excitation and an increased radiative decay rate, both
      contribute to the observed large enhancement. In accordance to our electric field
      modelling, however, excitation enhancement is the component that varies most with
      particle morphology. These findings provide important insights into the mechanism
      of MEF from AuNSs, and can be used to further guide particle design for high
      contrast enhancement, enabling the development of MEF biodetection technologies.

PMID- 30105339
TI  - Tuning Schottky barriers for monolayer GaSe FETs by exploiting a weak Fermi level
      pinning effect.
AB  - Monolayer gallium selenide (GaSe), an emerging two-dimensional semiconductor,
      holds great promise for electronics and optoelectronics. In reality, the contact
      properties between a semiconductor and the electrodes play a vital role in device
      performance. Thus, selecting suitable electrode materials with zero contact
      resistance is critical and challenging. Here, we explore the contact properties
      and electronic transport of monolayer GaSe with a series of electrode materials
      (including transition metals and MXenes) by ab initio electronic calculations and
      quantum transport simulations. Bare MXenes (V2C, Mo2C, Nb2C) and transition
      metals (Ni, Cu, Pt, Au) form strong chemical bonds with monolayer GaSe and lead
      to n-type contacts with Schottky barriers of 0-0.53 eV. The O-terminated MXenes
      (V2CO2 and Nb2CO2) establish van der Waals interactions with the GaSe sheet and
      form p-type contacts with vanishing hole Schottky barriers but large tunneling
      barriers. Impressively, Ohmic contact is achieved by the V2C and Mo2C electrodes,
      which is further demonstrated by the linear I-V curves. These contact systems
      exhibit a weak Fermi level pinning effect, with Schottky barriers in both the
      vertical and lateral directions controllable by the work function of the
      electrodes. To promote the carrier injection process, we propose to select
      electrode materials with a strong surface polarization and low work function
      (<5.0 eV) for GaSe-based devices.

PMID- 30105341
TI  - Distinguishing between two- and three-bond correlations for all 13C
      multiplicities in heteronuclear NMR spectroscopy.
AB  - A novel two-dimensional method, SEA XLOC, for distinguishing between two- and
      three-bond correlations in heteronuclear NMR spectroscopy is introduced and
      demonstrated on ibuprofen and by a complete set of correlations with a simple and
      most complex quaternary 13C multiplet in strychnine.

PMID- 30105340
TI  - Intracellular self-disassemble polysaccharide nanoassembly for multi-factors
      tumor drug resistance modulation of doxorubicin.
AB  - Drug efflux induced by multidrug resistance (MDR) overexpression, as well as
      secondary drug resistance caused by subtoxic drug microenvironments as a result
      of inefficient drug release of nanoscopic drug carriers in tumor cells, are major
      bottlenecks for chemotherapy. In order to overcome these limitations, we have
      devised a synergism-based polymer supramolecular nanoassembly (LH) by combining
      hyaluronic acid (HA) modified curcumin (HA-CUR) with a pH-sensitive low molecular
      weight heparin (LMWH) derivative modified doxorubicin (L-DOX). Our study proved
      that HA modification not only facilitated tumor targeting drug delivery
      efficiency through CD44 receptors-mediated active tumor-targeting strategy but
      also significantly enhanced the MDR reversion effect of CUR by improving its
      biological stability in different physiological environments. Also, the L-DOX in
      LH could trigger rapid and effective DOX release under a varied pH value
      environment, thereby overcoming secondary drug resistance. More importantly, a
      synergistic antitumor effect was achieved by optimizing the ratio of HA-CUR and L
      DOX in LH. Furthermore, LH showed a superior therapeutic effect over free DOX in
      two mouse models of human cancer. Taken together, these results demonstrated that
      LH might serve as an efficient platform for delivery of therapeutic payloads to
      overcome MDR.

PMID- 30105342
TI  - ExciTides: NTP-derived probes for monitoring pyrophosphatase activity based on
      excimer-to-monomer transitions.
AB  - We describe a new type of nucleotide-derived fluorescent probe designed for
      monitoring pyrophosphatase activity based on excimer-to-monomer transitions,
      called ExciTide. The nucleotides were designed with two self-interacting dye
      moieties and synthesised using copper-catalysed azide-alkyne cycloaddition click
      chemistry. We applied these probes for enzyme activity monitoring and inhibitor
      evaluation. Some of the probes permeated into living cells, yielding interesting
      prospects for future applications.

PMID- 30105344
TI  - Highly active bifunctional oxygen electrocatalysts derived from nickel- or cobalt
      phytic acid xerogel for zinc-air batteries.
AB  - Developing highly efficient non-noble metal electrocatalysts for oxygen electrode
      reactions is highly desirable for industrial scale application in energy related
      devices. Herein, two new kinds of Ni (POxN3-x)2/NPC and Co (POxN3-x)2/NPC (NPC:
      N, P-co-doped carbon) are synthesized through a facile post-treatment of nickel-
      or cobalt-phytic acid xerogel, followed by an annealing procedure under an argon
      and ammonia atmosphere at 800  degrees C. The as-prepared catalysts exhibit
      outstanding catalytic activities for both the oxygen reduction and evolution
      reactions, which are comparable to those of Pt/C and IrO2. Furthermore, the
      primary zinc-air batteries assembled with Ni (POxN3-x)2/NPC and Co (POxN3-x)2/NPC
      as the cathodes show gravimetric energy densities of 894 and 836 W h kgZn-1,
      which are superior to that of Pt/C (793 W h kgZn-1). In addition, the
      rechargeable zinc-air battery assembled with Ni (POxN3-x)2/NPC exhibits an
      excellent round-trip efficiency, which is shown by a slight increase in the sum
      of the overpotentials for discharge-charge cycling at a current density of 20 mA
      cm-2, even after experiencing 33 h of testing. To the best of our knowledge,
      there are few reports on metaphosphate salts where oxygen is partially replaced
      by nitrogen as bifunctional oxygen electrode catalysts for zinc-air batteries.
      This work provides an easy, low-cost and scalable avenue to develop new kinds of
      catalyst for application in energy devices.

PMID- 30105343
TI  - Triple-shelled NiMn2O4 hollow spheres as an efficient catalyst for low
      temperature selective catalytic reduction of NOx with NH3.
AB  - Unique triple-shelled NiMn2O4 hollow spheres are fabricated by a facile
      solvothermal method. Owing to its particular triple shell structure, the as
      prepared NiMn2O4 catalyst exhibits superior low-temperature NH3-SCR catalytic
      performance, achieving above 90% NOx conversion in the temperature range from 100
      degrees C to 225  degrees C.

PMID- 30105345
TI  - In vitro digestion profile and calcium absorption studies of a sea cucumber ovum
      derived heptapeptide-calcium complex.
AB  - In this study, a novel calcium-binding heptapeptide (NDEELNK) that is released
      during the trypsin hydrolysis of sea cucumber ovum was identified by peptidomics.
      The calcium binding mode, in vitro digestion profile and calcium absorption of
      the NDEELNK-calcium complex were investigated. The NDEELNK peptide could
      spontaneously bind calcium with a 1 : 1 stoichiometry, and the calcium-binding
      site might involve the carboxyl oxygen and amino nitrogen atoms of two glutamic
      acid and one aspartic acid residues in the NDEELNK peptide. The NDEELNK-calcium
      complex underwent disaggregation and self-aggregation in a mesh of smaller size
      during simulated gastrointestinal digestion, clarified by dynamic light
      scattering and confocal laser-scanning microscopy. In addition, the NDEELNK
      calcium complex could be conducive to calcium absorption across Caco-2 cell
      monolayers. The findings from this research suggest possible utilization of
      hydrolyzed peptides from sea cucumber ovum as dietary supplements to improve
      calcium absorption.

PMID- 30105347
TI  - Turning off Bacillus cereus quorum sensing system with peptidic analogs.
AB  - We explored quenching of the PlcR-PapR quorum-sensing system in Bacillus cereus.
      We generated PapR7-peptidic derivatives that inhibit this system and thus the
      production of virulence factors, reflected by a loss in hemolytic activity,
      without affecting bacterial growth. To our knowledge, these peptides represent
      the first potent synthetic inhibitors of quorum-sensing in B. cereus.

PMID- 30105348
TI  - Multiscale prediction of functional self-assembled materials using machine
      learning: high-performance surfactant molecules.
AB  - Various physical properties of functional materials can be induced by controlling
      their chemical molecular structures. Therefore, molecular design is crucial in
      the fields of engineering and materials science. With its remarkable development
      in various fields, machine learning combined with molecular simulation has
      recently been found to be effective at predicting the electronic structure of
      materials (Nat. Commun., 2017, 8, 872 and Nat. Commun., 2017, 8, 13890). However,
      previous studies have used similar microscale information as input and output
      data for machine learning, i.e., molecular structures and electronic structures.
      In this study, we determined whether multiscale data can be predicted using
      machine learning via a self-assembly functional material system. In particular,
      we investigated whether machine learning can be used to predict dispersion and
      viscosity, as the representative physical properties of a self-assembled
      surfactant solution, from the chemical molecular structures of a surfactant. The
      results showed that relatively accurate information on these physical properties
      can be predicted from the molecular structure, suggesting that machine learning
      can be used to predict multiscale systems, such as surfactant molecules, self
      assembled micelle structures, and physical properties of solutions. The results
      of this study will aid in further development of the application of machine
      learning to materials science and molecular design.

PMID- 30105350
TI  - Orthostatic Hypotension as a Prodromal Marker of alpha-Synucleinopathies-Reply.

PMID- 30105349
TI  - Amorphous titanic acid electrode: its electrochemical storage of ammonium in a
      new water-in-salt electrolyte.
AB  - We report an amorphous titanic acid of TiO1.85(OH)0.30.0.28H2O as a new electrode
      for aqueous ammonium-ion batteries, which operates in a new water-in-salt
      electrolyte-25 m NH4CH3COO. The titanic acid electrode exhibits a specific
      capacity nearly 8 times that from the crystalline TiO2 electrode. In
      electrochemical reactions, the amorphous titanic acid provides abundant storage
      sites in its disordered structure and affords strong H-bonding toward the
      inserted NH4+ ions.

PMID- 30105351
TI  - Dietary Measures to Prevent Sudden Unexpected Death in Epilepsy-Reply.

PMID- 30105353
TI  - Screening for Urinary Incontinence in Women: A Systematic Review for the Women's
      Preventive Services Initiative.
AB  - Background: Urinary incontinence is infrequently addressed during routine health
      care despite its high prevalence and adverse effects on health. Purpose: To
      evaluate whether screening for urinary incontinence in women not previously
      diagnosed improves outcomes (symptoms, quality of life, and function) and to
      evaluate the accuracy of screening methods and potential harms of screening. Data
      Sources: English-language searches of Ovid MEDLINE, Cochrane Central Register of
      Controlled Trials, and Cochrane Database of Systematic Reviews (1 January 1996 to
      30 March 2018); ClinicalTrials.gov (April 2018); and reference lists of studies
      and reviews. Study Selection: Randomized trials, cohort studies, systematic
      reviews of studies that enrolled nonpregnant women without previously diagnosed
      urinary incontinence and compared clinical outcomes and adverse effects between
      women who were and were not screened, and diagnostic accuracy studies that
      reported performance measures of screening tests. Data Extraction: Dual
      extraction and quality assessment of individual studies. Data Synthesis: No
      studies evaluated the overall effectiveness or harms of screening. Seventeen
      studies evaluated the diagnostic accuracy of 18 screening questionnaires against
      a clinical diagnosis or results of diagnostic tests. Of these, 14 poor-quality
      studies were based in referral clinics, enrolled only symptomatic women, or had
      other limitations. One good-quality and 2 fair-quality studies (evaluating 4
      methods) enrolled women not recruited on the basis of symptoms. Areas under the
      receiver-operating characteristic curve for stress, urge, and any type of
      incontinence in these studies were 0.79, 0.88, and 0.88 for the Michigan
      Incontinence Symptom Index; 0.85, 0.83, and 0.87 for the Bladder Control Self
      Assessment Questionnaire; and 0.68, 0.82, and 0.75 for the Overactive Bladder
      Awareness Tool. The Incontinence Screening Questionnaire had a sensitivity of 66%
      and specificity of 80% for any type of incontinence. Limitation: Studies enrolled
      few participants, often from symptomatic referral populations; used various
      reference standards; and infrequently reported CIs. Conclusion: Evidence is
      insufficient on the overall effectiveness and harms of screening for urinary
      incontinence in women. Limited evidence in general populations suggests fairly
      high accuracy for some screening methods. Primary Funding Source: Health
      Resources and Services Administration.

PMID- 30105354
TI  - Moving Beyond Symptom Remission to Optimize Long-term Treatment of Attention
      Deficit/Hyperactivity Disorder.

PMID- 30105352
TI  - Association Between Temporal Changes in Neonatal Mortality and Spontaneous and
      Clinician-Initiated Deliveries in the United States, 2006-2013.
AB  - Importance: Preterm and postterm deliveries have declined since 2005 in the
      United States, but the association between these changes and neonatal mortality
      remains unknown. Objective: To estimate changes in the gestational age
      distribution among spontaneous and clinician-initiated deliveries between 2006
      and 2013 and associated changes in neonatal mortality. Design, Setting, and
      Participants: A retrospective cohort analysis was conducted of 22 million
      singleton live births without major malformations in the United States from 2006
      to 2013. Data analysis was performed from August to October 2017. Main Outcomes
      and Measures: Changes in gestational age distribution among spontaneous and
      clinician-initiated deliveries at extremely preterm (20-27 weeks), very preterm
      (28-31 weeks), moderately preterm (32-33 weeks), late preterm (34-36 weeks),
      early term (37-38 weeks), term (39-40), late term (41 weeks), and postterm (42-44
      weeks) gestations and changes in neonatal mortality rates at less than 28 days
      between 2006 and 2013. These changes were estimated from log-linear Poisson
      regression models with robust variance, adjusted for confounders. Results: Among
      22 million births, 12 493 531 (56.7%) were spontaneous and 9 557 815 (43.3%) were
      clinician-initiated deliveries. Among spontaneous deliveries, the proportion of
      births at 20 to 27, 28 to 31, 32 to 33, 34 to 36, and 37 to 38 weeks declined.
      Among clinician-initiated deliveries, the proportion of births at 34 to 36 and 37
      to 38 weeks declined and the proportion at 39 to 40 weeks increased. Among
      spontaneous deliveries, overall neonatal mortality rates declined from 1.8 to 1.3
      per 1000 live births, mainly at 20 to 27 weeks (adjusted annual decline, 1%; 95%
      CI, -2% to -1%) and 28 to 31 weeks (adjusted annual decline, 6%; 95% CI, -8% to 
      5%). Among clinician-initiated deliveries, overall mortality rates remained
      unchanged (2.1 to 2.2 per 1000 live births). However, mortality rates declined
      (0.6 to 0.5 per 1000 live births) at 39 to 40 weeks by 1% (95% CI, -3% to -0.4%)
      annually, adjusted for confounders. Conclusions and Relevance: In the United
      States, there was a decline in spontaneous deliveries associated with an overall
      decline in neonatal mortality. Although clinician-initiated deliveries increased
      at 39 to 40 weeks, neonatal mortality at that gestation declined.

PMID- 30105355
TI  - Treatment of Acute Intoxication From Inhaled 1,2-Difluoroethane.

PMID- 30105356
TI  - Tinnitus Suppression in Cochlear Implant Patients Using a Sound Therapy App.
AB  - Purpose: The use of acoustic stimuli to reduce the prominence of tinnitus has
      been used for decades. Counseling and tinnitus sound therapy options are not
      currently widespread for cochlear implant (CI) users. The goal of this study was
      to determine whether tinnitus therapy sounds created for individuals with
      acoustic hearing may also benefit CI users. Method: Sixteen sounds from the
      ReSound Relief app (Version 3.0) were selected for the study. Sixteen
      participants were asked to rate the overall acceptability of each sound and to
      write the description of the sound they perceived. Sounds were streamed from an
      AppleTM iPod (6th generation) to the CI using a CochlearTM Wireless Mini
      Microphone 2+. Thirteen participants then completed a 5-min trial where they
      rated their pretrial and posttrial tinnitus and the acceptability of a subset of
      preferred sounds. Ten out of these 13 participants completed a 2-week home trial
      with a preferred sound after which they answered an online tinnitus questionnaire
      and rated the effectiveness of the sound therapy. Results: Individual differences
      were large. Results from the 5-min trial showed that sounds perceived as rain,
      music, and waves were rated the most acceptable. For all of the participants, the
      posttrial tinnitus loudness rating was lower than the pretrial rating, with some
      participants experiencing greater difference in their tinnitus loudness than
      others. At the end of the 2-week home trial, 3 of 10 participants rated the
      effectiveness of sound therapy 70% or higher. Conclusion: The results suggest
      that the use of tinnitus therapy sounds delivered through a CI can be acceptable
      and provides relief for some tinnitus sufferers.

PMID- 30105357
TI  - Determining Optimal Test Parameters for Assessing Dark Adaptation in People With
      Intermediate Age-Related Macular Degeneration.
AB  - Purpose: The primary aim was to determine optimal test conditions for evaluating
      dark adaptation in intermediate age-related macular degeneration (iAMD) in order
      to minimize test time while maintaining diagnostic sensitivity. Methods: People
      with AMD and age-similar controls were recruited (aged >55 years). Rod intercept
      time (RIT) was assessed after a 76%, 70%, and 65% rhodopsin bleach at 5 degrees 
      eccentricity and 76% and 70% bleach at 12 degrees . Test order was randomized and
      a 30-minute washout period added between tests. Results were compared between
      control and iAMD groups and receiver operating characteristics (ROC) curves were
      constructed. Results: A total of 26 participants with variable grades of macular
      health attended for two visits. There was a statistically significant difference
      in average RIT between the control and iAMD groups at 5 degrees  (median, IQR
      controls = 5.8 minutes, 3.8-7.5; iAMD = 20.6 minutes, 11.1-30.0; Mann-Whitney, P
      = 0.01) and at 12 degrees  (mean, controls: 4.54 minutes +/- 2.12 SD, iAMD = 7.72
      minutes +/- 3.37 SD; independent samples t-test, P = 0.03) following a 76%
      bleach. Area under the ROC curves was 0.83 (confidence interval [CI]: 0.64-1.0)
      and 0.79 (CI: 0.59-0.99) for these two test conditions, respectively. Five
      participants (45%) in the iAMD group had RITs >20 minutes for 76% bleach at 5
      degrees , but none for any other test condition. Conclusions: Nearly half of the
      participants with iAMD produced unacceptably long recovery times (>20 minutes)
      using a 76% bleach at 5 degrees  eccentricity. The 76% bleach at 12 degrees 
      provided almost equivalent separation between AMD and controls but recovery was
      achieved within 20 minutes.

PMID- 30105358
TI  - Orthostatic Hypotension as a Prodromal Marker of alpha-Synucleinopathies.

PMID- 30105359
TI  - Real-World Evidence and Real-World Data for Evaluating Drug Safety and
      Effectiveness.

PMID- 30105360
TI  - Screening for Urinary Incontinence in Women: A Recommendation From the Women's
      Preventive Services Initiative.
AB  - Description: Recommendation on screening for urinary incontinence in women by the
      Women's Preventive Services Initiative (WPSI), a national coalition of women's
      health professional organizations and patient representatives. The WPSI's
      recommendations are intended to guide clinical practice and coverage of services
      for the Health Resources and Services Administration and other stakeholders. The
      target audience for this recommendation includes all clinicians providing
      preventive health care for women, particularly in primary care settings. This
      recommendation applies to women of all ages, as well as adolescents. Methods: The
      WPSI developed this recommendation after evaluating evidence regarding the
      benefits and harms of screening for urinary incontinence in women. The evaluation
      included a systematic review of the accuracy of screening instruments and the
      benefits and harms of treatments. Indirect evidence was used to link screening
      and health outcomes in the chain of evidence that might support screening in the
      absence of direct evidence. The WPSI also considered the effect of screening on
      symptom progression and avoidance of costly and complex treatments, as well as
      implementation factors. Recommendation: The WPSI recommends screening women for
      urinary incontinence annually. Screening ideally should assess whether women
      experience urinary incontinence and whether it affects their activities and
      quality of life. The WPSI recommends referring women for further evaluation and
      treatment if indicated.

PMID- 30105361
TI  - Inconsistent Reporting of Potential Conflicts of Interest.

PMID- 30105362
TI  - Safety and Efficacy of Fludrocortisone in the Treatment of Cerebral Salt Wasting
      in Patients With Tuberculous Meningitis: A Randomized Clinical Trial.
AB  - Importance: Tuberculous meningitis is associated with high frequency of cerebral
      salt wasting. There is a paucity of objective information regarding the best
      method of treatment of this condition. Objective: To evaluate the efficacy and
      safety of fludrocortisone in the treatment of cerebral salt wasting in patients
      with tuberculous meningitis. Design, Setting, and Participants: This is a single
      center, open-label, randomized clinical trial conducted from October 2015 to
      April 2017 in India. Patients were randomized in a 1:1 ratio to arms receiving
      saline only or saline plus fludrocortisone, in addition to a standard treatment
      of 4 antitubercular drugs, prednisolone, and aspirin. The 2 arms were matched for
      demographic, clinical, and magnetic resonance imaging findings. The patients were
      followed up for at least 6 months. Interventions: Patients were randomized to a
      0.9% solution of intravenous saline with 5 to 12 g per day of oral salt
      supplementation, with or without the addition of 0.1 to 0.4 mg of fludrocortisone
      per day. Main Outcomes and Measures: The primary end point was the time needed to
      correct serum sodium levels; secondary end points were in-hospital deaths,
      disability at 3 months, disability at 6 months, occurence of stroke, and serious
      adverse reactions. Results: Ninety-three patients with suspected tuberculous
      meningitis were recruited; 12 did not meet the inclusion criteria, including 4
      with alternate diagnoses. A total of 37 patients with cerebral salt wasting were
      eligible for the study. One refused to participate, and therefore 36 patients
      were included, with 18 randomized to each group. The median (range) age was 30
      (20-46) years, and 19 were male (52.8%). Those receiving fludrocortisone regained
      normal serum sodium levels after 4 days, significantly earlier than those
      receiving saline only (15 days; P = .004). In an intention-to-treat analysis,
      hospital mortality, disability at 3 months, and disability at 6 months did not
      differ significantly, but fewer infarcts occurred in the deep border zone in the
      group receiving fludrocortisone (1 of 18 [6%]) vs those in the control arm (6 of
      18 [33%]; P = .04). Fludrocortisone was associated with severe hypokalemia and
      hypertension in 2 patients each, and pulmonary edema occurred in 1 patient. These
      adverse reactions necessitated discontinuation of fludrocortisone in 2 patients.
      Conclusions and Relevance: Fludrocortisone results in earlier normalization of
      serum sodium levels, but did not affect outcomes at 6 months. Fludrocortisone had
      to be withdrawn in 2 patients because of severe adverse effects. This study
      provides class II evidence on the role of fludrocortisone in treatment of
      hyponatremia associated with cerebral salt wasting in patients with tuberculous
      meningitis. Trial Registration: Clinical Trials Registry of India (ctri.nic.in)
      Identifier: CTRI/2017/10/010255.

PMID- 30105364
TI  - Tumor Necrosis Factor Inhibitors and Cancer Relapse.

PMID- 30105363
TI  - Performance of the Simplified American Academy of Pediatrics Table to Screen
      Elevated Blood Pressure in Children.

PMID- 30105365
TI  - Sodium-Glucose Cotransporter 2 Inhibitors and the Risk of Amputation: Results and
      Challenges From the Real World.

PMID- 30105366
TI  - Bariatric Surgery May Improve Type 2 Diabetes and Its Comorbidities by Reducing
      Interleukin 32 Levels.

PMID- 30105367
TI  - The Spectrum of Structural and Functional Abnormalities in Female Carriers of
      Pathogenic Variants in the RPGR Gene.
AB  - Purpose: The purpose of this study was to investigate the phenotype and long-term
      clinical course of female carriers of RPGR mutations. Methods: This was a
      retrospective cohort study of 125 heterozygous RPGR mutation carriers from 49
      families. Results: Eighty-three heterozygotes were from retinitis pigmentosa (RP)
      pedigrees, 37 were from cone-/cone-rod dystrophy (COD/CORD) pedigrees, and 5
      heterozygotes were from pedigrees with mixed RP/CORD or unknown diagnosis.
      Mutations were located in exon 1-14 and in ORF15 in 42 of 125 (34%) and 83 of 125
      (66%) subjects, respectively. The mean age at the first examination was 34.4
      years (range, 2.1 to 86.0 years). The median follow-up time in heterozygotes with
      longitudinal data (n = 62) was 12.2 years (range, 1.1 to 52.2 years). Retinal
      pigmentary changes were present in 73 (58%) individuals. Visual symptoms were
      reported in 51 (40%) cases. Subjects with both symptoms and pigmentary fundus
      changes were older than the other heterozygotes (P = 0.01) and had thinner foveal
      outer retinas (P = 0.006). Complete expression of the RP or CORD phenotype was
      observed in 29 (23%) heterozygotes, although usually in milder forms than in
      affected male relatives. Best-corrected visual acuity (BCVA) was <20/40 and
      <20/400 in at least one eye in 45 of 116 (39%) and 11 of 116 (9%) heterozygotes,
      respectively. Myopia was observed in 74 of 101 (73%) subjects and was associated
      with lower BCVA (P = 0.006). Increasing age was associated with lower BCVA (P =
      0.002) and decreasing visual field size (P = 0.012; I4e isopter). Conclusions:
      RPGR mutations lead to a phenotypic spectrum in female carriers, with myopia as a
      significantly aggravating factor. Complete disease expression is observed in some
      individuals, who may benefit from future (gene) therapeutic options.

PMID- 30105368
TI  - Increased Iris Stiffness in Patients With a History of Angle-Closure Glaucoma: An
      Image-Based Inverse Modeling Analysis.
AB  - Purpose: Previous studies have shown that iris mechanical properties may play a
      role in the pathophysiology of primary angle-closure glaucoma (PACG). Such
      studies, however, were not conducted in vivo and as such were limited in
      application and scope, especially for the development of diagnostic methods or
      new treatment options. The purpose of this study was to quantify in vivo iris
      mechanical properties both in patients with a history of angle-closure glaucoma
      and in healthy volunteers. Methods: We acquired optical coherence tomography
      scans of anterior segments under standard and dim light conditions. Using a
      combination of finite element simulation and an inverse fitting algorithm, we
      quantified the stiffness of the iris. Results: The irides in the eyes of patients
      with a history of PACG were significantly stiffer when compared with healthy
      control irides, a result consistent with ex vivo studies. This result was
      independent of the compressibility assumption (incompressible: 0.97 +/- 0.14 vs.
      2.72 +/- 0.71, P = 0.02; compressible: 0.89 +/- 0.13 vs. 2.57 +/- 0.69, P = 0.02)
      when comparing the normalized elastic modulus of the iris between patients with
      PACG and healthy controls. Conclusions: Our noninvasive, in vivo quantification
      is free of numerous ethical issues and potential limitations involved with ex
      vivo examinations. If further studies confirm that the iris stiffness is an
      omnipresent PACG risk factor and a mechanistic role between increased iris
      stiffness and angle-closure glaucoma does exist, treatment methods such as
      lowering the iris stiffness can be developed.

PMID- 30105369
TI  - An Optical Coherence Tomography Angiography Study of the Relationship Between
      Foveal Avascular Zone Size and Retinal Vessel Density.
AB  - Purpose: To assess the relationship between the size of the foveal avascular zone
      (FAZ; area and perimeter) and vessel density (VD) at various retinal regions
      using optical coherence tomography angiography (OCTA) in patients with open-angle
      glaucoma (OAG). Methods: In this retrospective cross-sectional study, OAG eyes
      were grouped according to the presence/absence of central visual field (CVF)
      defects. A control group of normal eyes was also included. OCTA images were
      obtained from the optic nerve (4.5 * 4.5 mm2) and macular (3 * 3 mm2) area, in
      which VDs were measured in the circumpapilla, parafovea, and fovea regions.
      Partial correlation analyses between FAZ parameters representing size and VDs at
      different retinal regions were performed. The correlation between FAZ parameters
      and macular ganglion cell-inner plexiform layer thickness (mGCIPLT) and CVF mean
      sensitivity (MS) was also assessed. For spatial correspondence, correlations
      between FAZ parameters and corresponding VD, mGCIPLT, and CVF-MS measurements
      were assessed at each hemiretina. Results: A total of 126 OAG eyes and 40
      controls were reviewed. Overall, FAZ parameters showed statistically significant
      correlations with VDs measured at the fovea, parafovea, and circumpapilla (FAZ
      area: r = -0.603, -0.385, -0.256; P < 0.001, < 0.001, and 0.003, respectively).
      These correlations were observed regardless of the presence of CVF defects (all P
      < 0.05). FAZ size showed significant spatial correlations with VD, mGCIPLT, and
      CVF-MS measurements at each hemiretina. Conclusions: OCTA-derived FAZ area and
      perimeter showed statistically significant correlations with VDs measured at
      various retinal locations with spatial correspondence in OAG.

PMID- 30105370
TI  - Subretinal Drusenoid Deposits and the Loss of Rod Function in Intermediate Age
      Related Macular Degeneration.
AB  - Purpose: To compare static rod function obtained with and without photobleach in
      control and intermediate age-related macular degeneration (iAMD) participants
      with and without subretinal drusenoid deposits (SDD). Methods: In this cross
      sectional study, retinal sensitivities within the central 24 degrees  retina were
      obtained twice using a dark-adapted chromatic perimeter, both with 505- and 625
      nm stimuli. Tests were performed after 30 minutes of dark-adaptation either with
      or without a preceding photobleach. Multimodal imaging was performed to grade AMD
      and SDD status, and other retinal changes considered being risk factors for
      progression to late AMD. The sensitivity difference between both stimuli was used
      to assess rod function. The average point wise sensitivity difference (PWSD) was
      compared among the study groups. Results: Twenty-nine control subjects and 20
      iAMD without SDD and 17 iAMD with SDD cases were recruited. The average PWSD of
      the SDD group was significantly reduced (more with photobleach) compared with
      that of the control (P < 0.001) and no-SDD groups (P < 0.001), but only within
      the central 8 degrees . The average PWSD of the non-SDD group was also reduced
      compared with the control group but only for measurements with photobleach (P =
      0.020). There was no difference in average PWSD between the presence and absence
      of hyperreflective foci and/or nascent geographic atrophy in iAMD eyes without
      SDD (P = 0.60) or with SDD (P = 0.12). Conclusions: iAMD eyes with SDD are
      associated with worse static rod function compared with eyes without SDD. The
      greatest abnormality in rods is observed within the central 8 degrees  and when
      tested with a preceding photobleach.

PMID- 30105371
TI  - Development of a Conceptual Map of Negative Consequences for Patients of Overuse
      of Medical Tests and Treatments.
AB  - Importance: Overuse of medical tests and treatments is an increasingly recognized
      problem across health systems; best practices for reducing overuse are not clear.
      Framing the problem in terms of the spectrum of potential patient harm is likely
      to be an effective strategy for clinician and patient engagement in efforts to
      reduce overuse, but the scope of negative consequences of overuse for patients
      has not been well described. Observations: We sought to generate a comprehensive
      conceptual map documenting the processes through which overused tests and
      treatments lead to multiple domains of negative consequences for patients. For
      map development, an iterative consensus process was informed by structured review
      of the literature on overuse using PubMed and input from a panel of 6
      international experts. For map verification, a systematic review was performed of
      case reports involving overused services, identified through literature review
      and manual review of relevant article collections. The conceptual map documents
      that overused tests and treatments and resultant downstream services generate 6
      domains of negative consequences for patients: physical, psychological, social,
      financial, treatment burden, and dissatisfaction with health care. Negative
      consequences can result from overused services and from downstream services; they
      can also trigger further downstream services that in turn can lead to more
      negative consequences, in an ongoing feedback loop. Case reports on overuse
      confirmed the processes and domains of the conceptual map. Cases also revealed
      strengths and weaknesses in published communication about overuse: they were
      dominated by physical harms, with other negative consequences receiving far less
      attention. Conclusions and Relevance: This evidence-based conceptual map
      clarifies the processes by which overused tests and treatments result in negative
      consequences for patients; it also documents multiple domains of negative
      consequences experienced by patients. The map will be useful for facilitating
      comprehensive communication about overuse, estimating harms and costs associated
      with overused services, and informing health system efforts to reduce overuse.

PMID- 30105372
TI  - Failing Grade for Shared Decision Making for Lung Cancer Screening.

PMID- 30105373
TI  - Association Between Sodium-Glucose Cotransporter 2 Inhibitors and Lower Extremity
      Amputation Among Patients With Type 2 Diabetes.
AB  - Importance: Results of clinical trials suggest that canagliflozin, a sodium
      glucose cotransporter 2 (SGLT-2) inhibitor for treating type 2 diabetes, may be
      associated with lower extremity amputation. Objective: To quantify the
      association between the use of oral medication for type 2 diabetes and 5 outcomes
      (lower extremity amputation, peripheral arterial disease, critical limb ischemia,
      osteomyelitis, and ulcer). Design, Setting, and Participants: A retrospective
      cohort study was conducted using Truven Health MarketScan Commercial Claims and
      Encounters data on new users between September 1, 2012, and September 30, 2015.
      The study focused on 2.0 million commercially insured individuals and used
      propensity score weighting to balance baseline differences among groups.
      Sensitivity analyses varied statistical models, assessed the effect of combining
      dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1)
      agonists as a single referent group, adjusted for baseline use of older oral
      agents, and included people with baseline amputation. Exposures: New use of SGLT
      2 inhibitors alone, DPP-4 inhibitors alone, GLP-1 agonists alone, or other
      antidiabetic agents (sulfonylurea, metformin hydrochloride, or
      thiazolidinediones). Main Outcomes and Measures: Foot and leg amputation, defined
      by validated International Classification of Diseases, Ninth Revision and Current
      Procedural Terminology codes. Results: Among 2.0 million potentially eligible
      individuals, a total of 953 906 (516 046 women and 437 860 men; mean [SD] age,
      51.8 [10.9] years) were included in the final analyses, including 39 869 new
      users of SGLT-2 inhibitors (4.2%), 105 023 new users of DPP-4 inhibitors (11.0%),
      and 39 120 new users of GLP-1 agonists (4.1%). The median observation time ranged
      from 99 days for new users of GLP-1 agonists to 127 days for those using
      metformin, sulfonylureas, and thiazolidinediones, while the crude incident rates
      ranged from 4.90 per 10 000 person-years for those using metformin,
      sulfonylureas, and thiazolidinediones to 10.53 per 10 000 person-years for new
      users of SGLT-2 inhibitors. After propensity score weighting and adjustment for
      demographics, severity of diabetes, comorbidities, and medications, there was a
      nonstatistically significant increased risk of amputation associated with new use
      of SGLT-2 inhibitors compared with DPP-4 inhibitors (adjusted hazard ratio, 1.50;
      95% CI, 0.85-2.67) and GLP-1 agonists (adjusted hazard ratio, 1.47; 95% CI, 0.64
      3.36). New use of SGLT-2 inhibitors was statistically significantly associated
      with amputation compared with sulfonylureas, metformin, or thiazolidinediones
      (adjusted hazard ratio, 2.12; 95% CI, 1.19-3.77). These results persisted in
      sensitivity analyses. Conclusions and Relevance: Use of SGLT-2 inhibitors may be
      associated with increased risk of amputation compared with some oral treatments
      for type 2 diabetes. Further observational studies are needed with extended
      follow-up and larger sample sizes.

PMID- 30105374
TI  - Tumor Necrosis Factor Inhibitors and Cancer Recurrence in Swedish Patients With
      Rheumatoid Arthritis: A Nationwide Population-Based Cohort Study.
AB  - Background: Use of tumor necrosis factor inhibitors (TNFi) in patients with a
      history of cancer remains a clinical dilemma. Objective: To investigate whether
      TNFi treatment in rheumatoid arthritis (RA) is associated with increased risk for
      cancer recurrence. Design: Population-based cohort study based on linkage of
      nationwide registers. Setting: Sweden. Participants: Patients with RA who started
      TNFi treatment between 2001 and 2015, after being diagnosed with cancer, and
      matched patients with RA and a history of the same cancer who had never received
      biologics. Measurements: The primary outcome was the first recurrence of cancer.
      Adjusted Cox proportional hazards models were used to estimate hazard ratios
      (HRs), taking into account time, cancer type, and whether the cancer was invasive
      or in situ (or tumor, node, metastasis [TNM] classification system stage in a
      subset of patients). Results: Among 467 patients who started TNFi treatment (mean
      time after cancer diagnosis, 7.9 years), 42 had cancer recurrences (9.0%; mean
      follow-up, 5.3 years); among 2164 matched patients with the same cancer history,
      155 had recurrences (7.2%; mean follow-up, 4.3 years) (HR, 1.06 [95% CI, 0.73 to
      1.54). Hazard ratios were close to 1 in analyses of patient subsets matched on
      cancer stage or with similar time from index cancer diagnosis to the start of
      TNFi treatment, as well as in unmatched analyses. Several CIs had upper limits
      close to 2. Limitation: The outcome algorithm was partly nonvalidated, and
      channeling bias was possible if patients with a better index cancer prognosis
      were more likely to receive TNFi. Conclusion: The findings suggest that TNFi
      treatment is not associated with increased risk for cancer recurrence in patients
      with RA, although meaningful risk increases could not be ruled out completely.
      Primary Funding Source: ALF (an agreement in Stockholm County Council concerning
      medical education and research in health and medical care), the Swedish Cancer
      Society, the Swedish Foundation for Strategic Research, and the Swedish Research
      Council.

PMID- 30105376
TI  - Retinoids and Amyotrophic Lateral Sclerosis.

PMID- 30105375
TI  - Real-Time Use of Artificial Intelligence in Identification of Diminutive Polyps
      During Colonoscopy: A Prospective Study.
AB  - Background: Computer-aided diagnosis (CAD) for colonoscopy may help endoscopists
      distinguish neoplastic polyps (adenomas) requiring resection from nonneoplastic
      polyps not requiring resection, potentially reducing cost. Objective: To evaluate
      the performance of real-time CAD with endocytoscopes (*520 ultramagnifying
      colonoscopes providing microvascular and cellular visualization of colorectal
      polyps after application of the narrow-band imaging [NBI] and methylene blue
      staining modes, respectively). Design: Single-group, open-label, prospective
      study. (UMIN [University hospital Medical Information Network] Clinical Trial
      Registry: UMIN000027360). Setting: University hospital. Participants: 791
      consecutive patients undergoing colonoscopy and 23 endoscopists. Intervention:
      Real-time use of CAD during colonoscopy. Measurements: CAD-predicted pathology
      (neoplastic or nonneoplastic) of detected diminutive polyps (<=5 mm) on the basis
      of real-time outputs compared with pathologic diagnosis of the resected specimen
      (gold standard). The primary end point was whether CAD with the stained mode
      produced a negative predictive value (NPV) of 90% or greater for identifying
      diminutive rectosigmoid adenomas, the threshold required to "diagnose-and-leave"
      nonneoplastic polyps. Best- and worst-case scenarios assumed that polyps lacking
      either CAD diagnosis or pathology were true- or false-positive or true- or false
      negative, respectively. Results: Overall, 466 diminutive (including 250
      rectosigmoid) polyps from 325 patients were assessed by CAD, with a pathologic
      prediction rate of 98.1% (457 of 466). The NPVs of CAD for diminutive
      rectosigmoid adenomas were 96.4% (95% CI, 91.8% to 98.8%) (best-case scenario)
      and 93.7% (CI, 88.3% to 97.1%) (worst-case scenario) with stained mode and 96.5%
      (CI, 92.1% to 98.9%) (best-case scenario) and 95.2% (CI, 90.3% to 98.0%) (worst
      case scenario) with NBI. Limitation: Two thirds of the colonoscopies were
      conducted by experts who had each experienced more than 200 endocytoscopies; 186
      polyps not assessed by CAD were excluded. Conclusion: Real-time CAD can achieve
      the performance level required for a diagnose-and-leave strategy for diminutive,
      nonneoplastic rectosigmoid polyps. Primary Funding Source: Japan Society for the
      Promotion of Science.

PMID- 30105377
TI  - Routine Screening for Urinary Incontinence in Women: Caution Advised.

PMID- 30105378
TI  - Making Colonoscopy Smarter With Standardized Computer-Aided Diagnosis.

PMID- 30105379
TI  - Screening for Urinary Incontinence in Women: A Recommendation From the Women's
      Preventive Services Initiative.

PMID- 30105380
TI  - Estimation of Overdiagnosis of Lung Cancer in Low-Dose Computed Tomography
      Screening.

PMID- 30105382
TI  - Potential Effects of Bariatric Surgery and Reduced Interleukin 32 Levels on Type
      2 Diabetes and Its Comorbidities.

PMID- 30105383
TI  - Accounting for the Harms of Lung Cancer Screening.

PMID- 30105381
TI  - Efficacy of an Empowerment-Based, Group-Delivered HIV Prevention Intervention for
      Young Transgender Women: The Project LifeSkills Randomized Clinical Trial.
AB  - Importance: The incidence of HIV infection among transgender women in the United
      States is extremely high, with young transgender women (YTW) at highest risk;
      condomless sex is the primary risk behavior for transmission. However, there are
      no published randomized clinical trials to date examining interventions to reduce
      sexual risk for HIV acquisition and transmission within this group. Objective: To
      determine the efficacy of a culturally specific, empowerment-based, and group
      delivered behavioral prevention intervention to reduce sexual risk for HIV
      acquisition and transmission in sexually active YTW aged 16 to 29 years. Design,
      Setting, and Participants: Randomized clinical efficacy trial of Project
      LifeSkills, a group-delivered, behavioral HIV prevention intervention, vs
      standard of care conducted among 190 sexually active YTW between March 26, 2012,
      and August 15, 2016, at community-based locations in Boston, Massachusetts, and
      Chicago, Illinois, to reduce sexual risk for HIV acquisition or transmission.
      Data analysis was by a modified intention-to-treat approach. Interventions:
      Participants were randomized (approximately 2:2:1) to the LifeSkills intervention
      (n = 116), standard of care only (n = 74), or a diet and nutrition time- and
      attention-matched control (attention control) arm (n = 43). The attention control
      arm was dropped during active enrollment per the Data Safety and Monitoring
      Board's recommendation. The LifeSkills intervention was delivered in six 2-hour
      sessions spanning a 3-week period. Main Outcomes and Measures: Primary outcome
      was change in the number of self-reported condomless anal or vaginal sex acts in
      the 4 months before the baseline assessment and that reported at the 4-, 8-, and
      12-month visits. Results: Of the 190 study participants, the mean (SD) age was
      23.4 (3.4) years (range, 16-29 years); 47 (24.7%) were white, 83 (43.7%) were
      black or African American, 25 (13.2%) were Hispanic or Latina, and 35 (18.4%)
      were another race/ethnicity. From baseline to 4 months, the LifeSkills group had
      a 30.8% greater mean (SE) reduction in condomless sex acts (2.26 [0.40] at
      baseline vs 1.22 [0.22] at 4 months) compared with the standard of care group
      (2.69 [0.59] at baseline vs 2.10 [0.47] at 4 months) (risk ratio [RR], 0.69; 95%
      CI, 0.60-0.80; P < .001). Similarly, the LifeSkills group had a 39.8% greater
      mean (SE) reduction in condomless sex acts at the 12-month follow-up visit
      compared with the standard of care group (0.71 [0.13] vs 1.40 [0.32]; RR, 0.60;
      95% CI, 0.50-0.72; P < .001). Conclusions and Relevance: Among YTW at sexual risk
      of HIV acquisition or transmission, the LifeSkills intervention resulted in a
      39.8% greater mean reduction in condomless sex acts during the 12-month follow-up
      in comparison to the standard of care group. This trial is the first to date to
      demonstrate evidence of efficacy for a behavioral intervention to reduce sexual
      risk in YTW. Trial Registration: ClinicalTrials.gov Identifier: NCT01575938.

PMID- 30105384
TI  - Rotavirus Vaccination and the Global Burden of Rotavirus Diarrhea Among Children
      Younger Than 5 Years.
AB  - Importance: Rotavirus infection is the global leading cause of diarrhea
      associated morbidity and mortality among children younger than 5 years.
      Objectives: To examine the extent of rotavirus infection among children younger
      than 5 years by country and the number of deaths averted because of the rotavirus
      vaccine. Design, Setting, and Participants: This report builds on findings from
      the Global Burden of Disease Study 2016, a cross-sectional study that measured
      diarrheal diseases and their etiologic agents. Models were used to estimate
      burden in data-sparse locations. Exposure: Diarrhea due to rotavirus infection.
      Main Outcomes and Measures: Rotavirus-associated mortality and morbidity by
      country and year and averted deaths attributable to the rotavirus vaccine by
      country. Results: Rotavirus infection was responsible for an estimated 128 500
      deaths (95% uncertainty interval [UI], 104 500-155 600) among children younger
      than 5 years throughout the world in 2016, with 104 733 deaths occurring in sub
      Saharan Africa (95% UI, 83 406-128 842). Rotavirus infection was responsible for
      more than 258 million episodes of diarrhea among children younger than 5 years in
      2016 (95% UI, 193 million to 341 million), an incidence of 0.42 cases per child
      year (95% UI, 0.30-0.53). Vaccine use is estimated to have averted more than 28
      000 deaths (95% UI, 14 600-46 700) among children younger than 5 years, and
      expanded use of the rotavirus vaccine, particularly in sub-Saharan Africa, could
      have prevented approximately 20% of all deaths attributable to diarrhea among
      children younger than 5 years. Conclusions and Relevance: Rotavirus-associated
      mortality has decreased markedly over time in part because of the introduction of
      the rotavirus vaccine. This study suggests that prioritizing vaccine introduction
      and interventions to reduce diarrhea-associated morbidity and mortality is
      necessary in the continued global reduction of rotavirus infection.

PMID- 30105386
TI  - Ensemble perception of facial attractiveness.
AB  - Ensemble perception, the extraction of a statistical summary of multiple
      instances of a feature, enables efficient processing of information. Here we
      investigated whether ensemble representations can be formed for facial
      attractiveness, a socially important complex feature. After verifying that our
      face stimuli produced by geometric morphing represented a valid continuum of
      attractiveness (Experiment 1), we asked participants to compare the average
      attractiveness of four faces with a single probe face. Whether the four faces
      were homogeneous or heterogeneous resulted in highly similar performance levels,
      suggesting the visual system could extract an ensemble representation of the
      attractiveness of a heterogeneous group of faces. Statistical simulations with
      human-level bias and noise indicated participants did not rely on subsampling one
      random face or the most/least attractive face from the array (Experiment 2).
      Ensemble perception of facial attractiveness was not affected by variance in the
      stimulus array (Experiment 3), did not depend on memory of individual faces in
      the array (Experiment 4), and could be extended to larger arrays with faces
      asymmetrically distributed around the set mean (Experiment 5). Our findings give
      further evidence to the prevalence of perception of statistical regularities in
      vision.

PMID- 30105387
TI  - Challenges and Successes in Evaluating HIV Prevention for Young Transgender Women
      Building Skills, Maintaining Trust.

PMID- 30105388
TI  - Metachromatic Leukodystrophy: Too Frequent (Mis)Diagnosis?-Reply.

PMID- 30105392
TI  - Dietary Measures to Prevent Sudden Unexpected Death in Epilepsy.

PMID- 30105385
TI  - Spatial summation in the human fovea: Do normal optical aberrations and
      fixational eye movements have an effect?
AB  - Psychophysical inferences about the neural mechanisms supporting spatial vision
      can be undermined by uncertainties introduced by optical aberrations and
      fixational eye movements, particularly in fovea where the neuronal grain of the
      visual system is fine. We examined the effect of these preneural factors on
      photopic spatial summation in the human fovea using a custom adaptive optics
      scanning light ophthalmoscope that provided control over optical aberrations and
      retinal stimulus motion. Consistent with previous results, Ricco's area of
      complete summation encompassed multiple photoreceptors when measured with
      ordinary amounts of ocular aberrations and retinal stimulus motion. When both
      factors were minimized experimentally, summation areas were essentially
      unchanged, suggesting that foveal spatial summation is limited by postreceptoral
      neural pooling. We compared our behavioral data to predictions generated with a
      physiologically-inspired front-end model of the visual system, and were able to
      capture the shape of the summation curves obtained with and without pre-retinal
      factors using a single postreceptoral summing filter of fixed spatial extent.
      Given our data and modeling, neurons in the magnocellular visual pathway, such as
      parasol ganglion cells, provide a candidate neural correlate of Ricco's area in
      the central fovea.

PMID- 30105394
TI  - Promoting Patient Interests in Implementing the Federal Right to Try Act.

PMID- 30105395
TI  - Retinoids and Amyotrophic Lateral Sclerosis-Reply.

PMID- 30105393
TI  - Evaluating Shared Decision Making for Lung Cancer Screening.
AB  - Importance: The US Preventive Services Task Force recommends that shared decision
      making (SDM) involving a thorough discussion of benefits and harms should occur
      between clinicians and patients before initiating lung cancer screening (LCS)
      with low-dose computed tomography. The Centers for Medicare & Medicaid Services
      require an SDM visit using a decision aid as a prerequisite for LCS coverage.
      However, little is known about how SDM about LCS occurs in practice. Objective:
      To assess the quality of SDM about the initiation of LCS in clinical practice.
      Design, Setting, and Participants: A qualitative content analysis was performed
      of transcribed conversations between primary care or pulmonary care physicians
      and 14 patients presumed to be eligible for LCS, recorded between April 1, 2014,
      and March 1, 2018, that were identified within a large database. Main Outcomes
      and Measures: Independent observer ratings of communication behaviors of
      physicians using the OPTION (Observing Patient Involvement in Decision Making)
      scale, a validated 12-item measure of SDM (total score, 0-100 points, where 0
      indicates no evidence of SDM and 100 indicates evidence of SDM at the highest
      skill level); time spent discussing LCS during visits; and evidence of decision
      aid use. Results: A total of 14 conversations about initiating LCS were
      identified; 9 patients were women, and 5 patients were men; the mean (SD) patient
      age was 63.9 (5.1) years; 7 patients had Medicare, and 8 patients were current
      smokers. Half the conversations were conducted by primary care physicians. The
      mean total OPTION score for the 14 LCS conversations was 6 on a scale of 0 to 100
      (range, 0-17). None of the conversations met the minimum skill criteria for 8 of
      the 12 SDM behaviors. Physicians universally recommended LCS. Discussion of harms
      (such as false positives and their sequelae or overdiagnosis) was virtually
      absent. The mean total visit length of a discussion was 13:07 minutes (range,
      3:48-27:09 minutes). The mean time spent discussing LCS was 0:59 minute (range,
      0:16-2:19 minutes), or 8% of the total visit time (range, 1%-18%). There was no
      evidence that decision aids or other patient education materials for LCS were
      used. Conclusions and Relevance: In this small sample of recorded encounters
      about initiating LCS, the observed quality of SDM was poor and explanation of
      potential harms of screening was virtually nonexistent. Time spent discussing LCS
      was minimal, and there was no evidence that decision aids were used. Although
      these findings are preliminary, they raise concerns that SDM for LCS in practice
      may be far from what is intended by guidelines.

PMID- 30105396
TI  - Association of Intracranial Hemorrhage Risk With Non-Vitamin K Antagonist Oral
      Anticoagulant Use vs Aspirin Use: A Systematic Review and Meta-Analysis.
AB  - Importance: Non-vitamin K antagonist oral anticoagulants (NOACs) might be an
      attractive choice for stroke prevention in people without atrial fibrillation who
      may harbor a potential source of cardiac emboli, but not if certain individual
      NOACs carry risks of intracranial hemorrhage that are heightened relative to
      aspirin. Objective: To conduct a systematic review and meta-analysis of
      randomized clinical trials to assess the risk of intracranial hemorrhage with
      individual NOACs vs aspirin across all indications. Data Sources: We searched
      PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to May 28, 2018,
      with the terms novel oral anticoagulants, non-vitamin K antagonist oral
      anticoagulants, direct oral anticoagulants, dabigatran, rivaroxaban, apixaban,
      edoxaban, warfarin, Coumadin, vitamin K antagonist, aspirin, acetylsalicylic
      acid, or ASA, and major bleeding, fatal bleeding, or intracranial hemorrhage. We
      restricted our search to clinical trials on humans. There were no language
      restrictions. Study Selection: Randomized clinical trials of 3 months or longer
      that included a comparison of the outcomes of NOAC use vs use of aspirin. Data
      Extraction and Synthesis: Two investigators independently abstracted data from
      eligible studies. We computed a fixed-effect estimate based on the Mantel
      Haenszel method. Main Outcomes and Measures: Odds ratios (ORs) with 95% CI were
      used as a measure of the association of individual NOAC vs aspirin with the risk
      of intracranial hemorrhage. The hypothesis that intracranial hemorrhage risk
      would be higher with NOACs than aspirin was formulated during data collection.
      Results: Our principal analysis included 5 randomized clinical trials comparing 1
      or more NOACs with aspirin, with 39 398 individuals enrolled. Pooling the results
      from the fixed-effects model showed that a dose of 15 to 20 mg of rivaroxaban
      once daily was associated with an increased risk of intracranial hemorrhage (2
      trials; OR, 3.31 [95% CI, 1.42 to 7.72]) compared with aspirin, while a 10-mg
      dose of rivaroxaban once daily or a 5-mg dose twice daily (3 trials; OR, 1.43
      [95% CI, 0.93 to 2.21]) and a 5-mg dose of apixaban twice daily (1 trial; OR,
      0.84 [95% CI, 0.38 to 1.88]) were not. Conclusions and Relevance: A 15-mg to 20
      mg dose of rivaroxaban once daily is associated with substantially increased
      risks of intracranial hemorrhage, while smaller daily doses of rivaroxaban and
      apixaban were not, implying that risk increase is dose dependent. It may be
      worthwhile to conduct randomized clinical trials comparing specific NOACs in
      specific doses (eg, apixaban, 5 mg twice daily) and aspirin in patients without
      atrial fibrillation, but with potential sources of cardiac emboli that could
      cause stroke.

PMID- 30105397
TI  - Missing Conflict of Interest Disclosure.

PMID- 30105398
TI  - [Leadless pacemakers and subcutaneously implantable cardioverter defibrillators].
AB  - Although pacemakers and implantable defibrillators have become the standard
      treatment of bradycardic and tachycardic arrhythmias, long-term complications
      caused by the transvenously inserted pacing and defibrillation leads, such as
      electrode fracture, lead infection and tricuspid valve insufficiency are not
      uncommonly observed. Therefore, leadless pacemakers and purely subcutaneously
      implantable cardioverter defibrillators (S-ICDs) have been developed in recent
      years, which are implanted without transvenous electrodes with the aim to reduce
      long-term complications with these devices; however, currently available leadless
      pacemakers are limited to single chamber stimulation and S-ICDs are limited to
      pure defibrillation without antibradycardic, antitachycardic pacing or cardiac
      resynchronization capabilities. Thus, these devices cannot yet be used as
      multichamber pacemakers or defibrillators even though in these circumstances a
      higher complication rate is to be expected due to the multiple number of
      transvenous leads. This article summarizes the current state of knowledge on
      leadless pacemakers and ICDs, discusses the limitations of these devices and
      provides an outlook into their future development.

PMID- 30105399
TI  - Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking
      style and their association with ego dissolution.
AB  - RATIONALE: Ayahuasca is a psychotropic plant tea from South America used for
      religious purposes by indigenous people of the Amazon. Increasing evidence
      indicates that ayahuasca may have therapeutic potential in the treatment of
      mental health disorders and can enhance mindfulness-related capacities. Most
      research so far has focused on acute and sub-acute effects of ayahuasca on mental
      health-related parameters and less on long-term effects. OBJECTIVES: The present
      study aimed to assess sub-acute and long-term effects of ayahuasca on well-being
      and cognitive thinking style. The second objective was to assess whether sub
      acute and long-term effects of ayahuasca depend on the degree of ego dissolution
      that was experienced after consumption of ayahuasca. RESULTS: Ayahuasca ceremony
      attendants (N = 57) in the Netherlands and Colombia were assessed before, the day
      after, and 4 weeks following the ritual. Relative to baseline, ratings of
      depression and stress significantly decreased after the ayahuasca ceremony and
      these changes persisted for 4 weeks. Likewise, convergent thinking improved post
      ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and
      several aspects of mindfulness increased the day after the ceremony, but these
      changes failed to reach significance 4 weeks after. Changes in affect,
      satisfaction with life, and mindfulness were significantly correlated to the
      level of ego dissolution experienced during the ayahuasca ceremony and were
      unrelated to previous experience with ayahuasca. CONCLUSION: It is concluded that
      ayahuasca produces sub-acute and long-term improvements in affect and cognitive
      thinking style in non-pathological users. These data highlight the therapeutic
      potential of ayahuasca in the treatment of mental health disorders, such as
      depression.

PMID- 30105401
TI  - The "teardrop sign".

PMID- 30105400
TI  - The effects of teriparatide on acceleration of bone healing following atypical
      femoral fracture: comparison between daily and weekly administration.
AB  - : We compared the effectiveness of promoting bone healing between two
      teriparatide preparations for atypical femoral fracture (AFF). A total of 45 AFFs
      were included in this study, and we compared the duration of bone union.
      Teriparatide administered by daily injection enhanced bone union more than weekly
      administration in complete AFFs. INTRODUCTION: The efficacy of teriparatide for
      atypical femoral fracture (AFF) has been recently reported. Although two
      different teriparatide preparations can be used to treat osteoporosis in Japan,
      daily or weekly injection, all previous reports on the effectiveness of
      teriparatide for AFF only examined daily injection formulations. Therefore, we
      compared the promotion of bone healing between the two teriparatide preparations
      for AFF. METHODS: A total of 45 consecutive AFFs in 43 Japanese patients were
      included in this study. They received either a daily 20-MUg teriparatide
      injection (daily group; n = 32) or a once-a-week 56.5-MUg teriparatide injection
      (weekly group; n = 13). We compared the clinical background and duration of bone
      union between these two groups. RESULTS: When all patents were included, the
      fracture healing time was not significantly different between the two groups.
      Only patients with complete AFFs had significantly fewer daily bisphosphonate or
      denosumab injections than the weekly group (P < 0.05). The fracture healing time
      in the daily group (6.1 +/- 4.1 months) was significantly shorter than that in
      the weekly group (10.1 +/- 4.2 months) (P < 0.05). Even if the influence of
      bisphosphonate or denosumab usage was excluded, a similar significant difference
      was observed in the fracture healing time (P < 0.05). There was no significant
      difference between the two groups among patients with incomplete AFFs.
      CONCLUSIONS: Daily teriparatide injections enhance bone union more than weekly
      injections in complete AFF patients.

PMID- 30105402
TI  - Effect of triphenylphosphonium moiety on spatial structure and biointeractions of
      stereochemical variants of YRFK motif.
AB  - Chemical modification of therapeutic peptides is an important approach to
      improving their physicochemical and pharmacokinetic properties. The
      triphenylphosphonium (TPP) cation has proved to be a powerful modifier; however,
      its effects on peptide structure and activity remain uncharacterized. In this
      study, cytoprotective tetrapeptides based on the YRFK opioid motif with L- or D
      Arg residues were linked to (triphenylphosphonio)carboxylic acids with ethylene
      and pentylene spacers (TPP-3 and TPP-6 groups, respectively). The three
      dimensional structure of the oligopeptides was analyzed by NMR spectroscopy,
      computational methods and circular dichroism (CD). A more compact and bent
      structure with segregated aromatic groups was revealed for the D-arginine
      containing tetrapeptide and its TPP-6 derivative. The TPP moiety caused structure
      organizing effect on the tetrapeptides, resulting in transition from random coil
      to beta-sheet structures, and decreased the peptide backbone flexibility up to
      ten times. The TPP-3-modified oligopeptide with the lowest RMSD value (ca. 0.05
      A) was characterized by intrapeptide hydrophobic interactions between the TPP and
      side groups of Tyr and Phe residues accompanied by strong CD induction. The TPP-6
      modified oligopeptides showed enhanced ability to form intermolecular associates
      and disturb liposomal membranes. The relationship between the spatial structure
      of the oligopeptides and some of their biologically relevant interactions were
      additionally revealed and are discussed.

PMID- 30105403
TI  - Esophageal Lung in Association with Pulmonary Vascular Anomalies.
AB  - We present a 7.8-month-old girl with recurrent pneumonia, growth retardation, and
      tachypnea. Computed tomography revealed a particularly unusual esophageal lung,
      in association with pulmonary vascular anomalies of right pulmonary veins atresia
      and right pulmonary artery hypoplasia.

PMID- 30105404
TI  - The course of lower cranial nerves within the neck: a cadaveric dissection study.
AB  - PURPOSE: To evaluate the course of lower cranial nerves (CNs) within the neck in
      relation to surrounding structures and anatomic landmarks via a cadaveric
      dissection study. METHODS: A total of 70 neck dissections (31 bilateral, 8
      unilateral) were performed on 39 adult fresh cadavers [mean (SD) age: 38.5 (11.2)
      years, 29 male, 10 female] to identify the course of lower CNs [spinal accessory
      nerve (SAN), vagus nerve and hypoglossal nerve] within the neck in relation to
      surrounding structures [internal jugular vein (IJV), common carotid artery (CCA)]
      and distance to anatomical landmarks (cricoid cartilage, hyoid bone, digastric
      muscle). RESULTS: SAN travelled most commonly anterior to IJV (51.4%) at the
      level of jugular foramen, while travelling lateral to IJV at the post belly of
      digastric (55.7%) and inferior to digastric muscle (90%) in most neck
      dissections. Vagus nerve travelled lateral to CCA in majority (94.3%) of
      dissections, while medial (2.9%), posterolateral (1.4%) and posterior (1.4%)
      positions were also noted. Average distance of hypoglossal nerve was 27.7 (9.7)
      mm to carotid bifurcation, 9.3 (3.9) mm to hyoid bone, and 54.7 (18.0) mm to the
      inferior border of cricoid cartilage. CONCLUSION: In conclusion, our findings
      indicate that anatomic variations are not rare in the course of lower CNs within
      the neck in relation to adjacent structures, and awareness of these variations
      together with knowledge of distance to certain anatomic landmarks may help the
      surgeon to identify lower CNs during neck surgery and prevent potential nerve
      injuries.

PMID- 30105406
TI  - In vitro expression and functional characterization of NPA motifs in aquaporins
      of Nosema bombycis.
AB  - Nosema bombycis contains functional aquaporins (NbAQPs), which are key targets
      for exploring the mechanism of N. bombycis infection; however, the regulation of
      these NbAQPs remains unknown. The two highly conserved asparagine-proline-alanine
      sequences (NPA motifs) play important roles in AQP biogenesis. As part of this
      study, we constructed a series of NbAQP mutants (NbAQP_NPA1, NbAQP_NPA2, and
      NbAQP_NPA1,2) and expressed them in BmN cells. The results showed that mutations
      in either NPA motif or in both NPA motifs did not affect NbAQP expression in
      vitro. After expression in Xenopus laevis oocytes, those injected with wild-type
      NbAQP rapidly expanded, whereas oocytes injected with NbAQP_NPAs did not
      significantly change in size. The associated water permeability (pf) of
      NbAQP_NPAs was significantly reduced five-six times compared to that of wild-type
      NbAQP. These results indicated that NPA motifs are necessary for the water
      channel function of AQPs in N. bombycis. The present study shows for the first
      time that the NbAQP NPA motif has an impact on the water permeability of
      aquaporin in N. bombycis, thereby providing a platform for further research into
      the mechanisms underlying the regulation of NbAQP expression.

PMID- 30105407
TI  - Estimating soil heavy metals concentration at large scale using visible and near
      infrared reflectance spectroscopy.
AB  - This study was aimed (i) to examine using diffuse reflectance spectra within VNIR
      region to estimate soil heavy metals concentrations at large scale, (ii) to
      compare the influence of different pre-processing models on predictive model
      accuracy, and (iii) to explore the best predictive models. A number of 325
      topsoil samples were collected and their spectral data, pH, clay content, organic
      matter, Ni, and Cu concentrations were determined. To improve spectral data,
      various pre-processing methods including Savitzky-Golay smoothing filter,
      Savitzky-Golay smoothing filter with first and second derivatives, and standard
      normal variant (SNV) were used. Partial least squares regression (PLSR),
      principal component regression (PCR), and support vector machine regression
      (SVMR) models were employed to build calibration models for estimating soil heavy
      metals concentration followed by evaluation of provided predictive models.
      Results indicated that Cu had stronger correlation coefficients with spectral
      bands compared to Ni. Cu and Ni demonstrated strongest correlations at
      wavelengths 1925 and 1393 nm, respectively. Based on RMSE, R2, and RPD
      statistics, the PLSR model with Savitzky-Golay filter pretreatment provided the
      most accurate predictions for both Cu and Ni (R2 = 0.905, RMSE = 0.00123, RPD =
      2.80 for Ni; R2 = 0.825, RMSE = 0.00467, RPD = 2.04 for Cu) where such prediction
      was much better for Ni than for Cu. Reasonable results with lower accuracy and
      stability were obtained for PCR (R2 = 0.742, RMSE = 0.00181, RPD = 1.91 for Ni;
      R2 = 0.731, RMSE = 0.00578, RPD = 1.65 for Cu) and SVMR (R2 = 0.643, RMSE =
      0.00091, RPD = 3.80 for Ni; R2 = 0.505, RMSE = 0.00296, RPD = 3.22 for Cu). We
      concluded that reflectance spectroscopy technique could be applied as a reliable
      tool for detection and prediction of soil heavy metals.

PMID- 30105405
TI  - Population structures of Leishmania infantum and Leishmania tropica the causative
      agents of kala-azar in Southwest Iran.
AB  - Visceral leishmaniasis (VL) is endemic in Iran and is caused predominantly by
      Leishmania infantum, but L. tropica is emerging as an important cause. We studied
      the intra-species population structure of Leishmania spp. causing VL in southwest
      Iran by sequence analysis of the internal transcribed spacer (ITS) 1 of DNA
      samples from 29 bone marrow aspiration smears. L. infantum (n = 25) and L.
      tropica (n = 4) were identified, consisting of 10 and three ITS1 sequence types
      (STs), respectively. Compared to GenBank ITS1 STs, our L. infantum parasites
      displayed high heterogeneity but less heterogeneity compared than northwest
      Iranian isolates. VL affects mostly nomadic populations in southwest Iran, and
      their mobility may explain partly the L. infantum heterogeneity. The VL causing
      L. tropica was also genetically heterogeneous but genetically indistinguishable
      from L. tropica strains causing anthroponotic cutaneous leishmaniasis from
      southwest Iran.

PMID- 30105408
TI  - Evaluation of liver parenchyma stiffness in patients with liver tumours: optimal
      strategy for shear wave elastography.
AB  - OBJECTIVES: To determine the methodology of non-invasive test for evaluation of
      liver stiffness (LS) with tumours using two-dimensional (2D) shear wave
      elastography (SWE). METHODS: One hundred and twenty-seven patients with liver
      tumours underwent 2D-SWE before surgery to measure liver and spleen stiffness
      (SS). Two-dimensional SWE values were obtained in the liver at 0-1 cm, 1-2 cm and
      >2 cm from the tumour edge (PLS-1, PLS-2 and RLS, respectively). The influence of
      tumour-associated factors was evaluated. The area under the receiver operating
      characteristic curve (AUC) for each value was analysed to diagnose cirrhosis.
      RESULTS: PLS-1 was higher than PLS-2, which was even higher than RLS (p < 0.001).
      The AUCs of PLS-1, PLS-2, RLS and SS for diagnosing cirrhosis were 0.760, 0.833,
      0.940 and 0.676, with the specificity of 75.7%, 67.6%, 90.3% and 77.4%,
      respectively. Tumour sizes, locations or types showed no apparent influence on 2D
      SWE values except for RLS, which was higher in patients with primary hepatic
      carcinomas (p < 0.05). CONCLUSIONS: LS with tumours is best measured at >2 cm
      away from the tumour edge. SS measurement could be used as an alternative to LS
      measurement in the event of no available liver for detection. KEY POINTS: *
      Tumour-associated factors impact background liver stiffness assessment. *
      Background liver stiffness is best measured at >2 cm from tumour edge. * Spleen
      stiffness can be an alternative to assess background liver stiffness.

PMID- 30105409
TI  - Decreased cerebral blood flow and improved cognitive function in patients with
      end-stage renal disease after peritoneal dialysis: An arterial spin-labelling
      study.
AB  - OBJECTIVES: The aim of this study was to evaluate the relationship between
      cognitive impairment and brain perfusion using arterial spin labelling (ASL) in
      end-stage renal disease (ESRD) patients undergoing PD. METHODS: ESRD patients
      undergoing PD were recruited. Laboratory screening, neuropsychological tests and
      ASL magnetic resonance imaging (MRI) were conducted prior to and after 6 months
      of PD. Age- and sex-matched normal subjects without ESRD served as the control
      group. Comparisons of regional CBF between ESRD patients before or after
      undergoing PD and normal controls were performed. Correlations between
      biochemical, neuropsychological and CBF data were also conducted to evaluate the
      relationships. RESULTS: ESRD patients showed poor performance in many of the
      neuropsychological tests; PD improved cognition in some domains. Pre-PD patients
      had higher mean CBF than post-PD patients and normal controls, but no significant
      difference was found between the normal controls and post-PD patients. Negative
      correlations were observed pre-PD (regional CBF in left hippocampus vs.
      perseverative responses, r = -0.662, p = 0.014), post-PD (mean CBF vs.
      haemoglobin level, r = -0.766, p = 0.002), and before and after PD (change in CBF
      in the left putamen vs. change in haematocrit percentage, r = -0.808, p = 0.001).
      CONCLUSION: Before PD, ESRD patients had increased cerebral perfusion that was
      related to poorer executive function, especially in the left hippocampus. Post-PD
      patients performed better in some cognitive test domains than pre-PD patients.
      The degree of anaemia, i.e., haemoglobin level or haematocrit percentage, might
      predict cognitive impairment in PD patients. KEY POINTS: * In this study, ESRD
      patients before PD had cerebral hyperperfusion that was related to poorer
      executive function. * Post-PD patients performed better in some cognitive test
      domains than pre-PD patients did. * The degree of anaemia might predict cognitive
      impairment in PD patients.

PMID- 30105410
TI  - Demystification of AI-driven medical image interpretation: past, present and
      future.
AB  - : The recent explosion of 'big data' has ushered in a new era of artificial
      intelligence (AI) algorithms in every sphere of technological activity, including
      medicine, and in particular radiology. However, the recent success of AI in
      certain flagship applications has, to some extent, masked decades-long advances
      in computational technology development for medical image analysis. In this
      article, we provide an overview of the history of AI methods for radiological
      image analysis in order to provide a context for the latest developments. We
      review the functioning, strengths and limitations of more classical methods as
      well as of the more recent deep learning techniques. We discuss the unique
      characteristics of medical data and medical science that set medicine apart from
      other technological domains in order to highlight not only the potential of AI in
      radiology but also the very real and often overlooked constraints that may limit
      the applicability of certain AI methods. Finally, we provide a comprehensive
      perspective on the potential impact of AI on radiology and on how to evaluate it
      not only from a technical point of view but also from a clinical one, so that
      patients can ultimately benefit from it. KEY POINTS: * Artificial intelligence
      (AI) research in medical imaging has a long history * The functioning, strengths
      and limitations of more classical AI methods is reviewed, together with that of
      more recent deep learning methods. * A perspective is provided on the potential
      impact of AI on radiology and on its evaluation from both technical and clinical
      points of view.

PMID- 30105411
TI  - Diagnosis of transition zone prostate cancer using T2-weighted (T2W) MRI:
      comparison of subjective features and quantitative shape analysis.
AB  - PURPOSE: To assess T2-weighted (T2W) MRI to differentiate transition zone (TZ)
      prostate cancer (PCa) from benign prostatic hyperplasia (BPH). MATERIALS AND
      METHODS: With IRB approval, 22 consecutive TZ PCa were retrospectively compared
      with 30 consecutive BPH (15 stromal, 15 glandular) nodules diagnosed using
      radical prostatectomy MRI maps. Two blinded radiologists (R1/R2) subjectively
      assessed the shape (round/oval vs. lenticular) and margin (circumscribed vs.
      blurred/indistinct) and for a T2W hypointense rim. Both radiologists segmented
      lesions extracting quantitative shape features (circularity, convexity and
      topology/skeletal branching). Statistical tests were performed using chi-square
      (subjective features), Mann-Whitney U (quantitative features), Cohen's
      kappa/Bland-Altman and receiver-operator characteristic analysis. RESULTS: There
      were differences in the subjective analysis of the shape, margin and absence of a
      T2W-rim comparing TZ PCa with BPH (p < 0.0001) with moderate to almost perfect
      agreement [kappa = 0.56 (shape), 0.72 (margin), 0.97 (T2W-rim)]. Area under the
      curve (AUC +/- standard error) for diagnosis of TZ PCas was shape = 0.88 +/-
      0.05, margin = 0.89 +/- 0.04, and T2W-rim = 0.91 +/- 0.04. Shape, judged
      subjectively, was specific (100%/94% R1/R2) with low-to-moderate sensitivity
      (55%/88% R1/R2). Circularity and convexity differed between groups (p < 0.001)
      with no difference in topology/skeletal branches (p = 0.31). Agreement in
      measurements was substantial for significant quantitative variables and AUC +/-
      SE, sensitivity and specificity for diagnosis of TZ PCa were: circularity = 0.98
      +/- 0.01, 90%/96%; convexity = 0.85 +/- 0.06, 68%/97%. AUCs for circularity were
      higher than for subjective analysis (p = 0.01 and 0.26). CONCLUSION: Subjective
      analysis of T2W-MRI accurately diagnoses TZ PCa with high accuracy also
      demonstrated for quantitative shape analysis, which may be useful for future
      radiogenomic analysis of transition zone tumors. KEY POINTS: * Presence of a
      complete T2-weighted hypointense circumscribed rim accurately diagnoses BPH. *
      Round shape accurately diagnoses BPH and can be assessed quantitatively using
      circularity. * Lenticular shape accurately diagnoses TZ PCa and can be assessed
      quantitatively using convexity.

PMID- 30105413
TI  - Oxidative stress in autosomal dominant polycystic kidney disease: player and/or
      early predictor for disease progression?
AB  - Autosomal dominant polycystic kidney disease (ADPKD), caused by mutations in PKD1
      or PKD2 genes, is the most common hereditary renal disease. Renal manifestations
      of ADPKD are gradual cyst development and kidney enlargement ultimately leading
      to end-stage renal disease. ADPKD also causes extrarenal manifestations,
      including endothelial dysfunction and hypertension. Both of these complications
      are linked with reduced nitric oxide levels related to excessive oxidative stress
      (OS). OS, defined as disturbances in the prooxidant/antioxidant balance, is
      harmful to cells due to the excessive generation of highly reactive oxygen and
      nitrogen free radicals. Next to endothelial dysfunction and hypertension, there
      is cumulative evidence that OS occurs in the early stages of ADPKD. In the
      current review, we aim to summarize the cardiovascular complications and the
      relevance of OS in ADPKD and, more specifically, in the early stages of the
      disease. First, we will briefly introduce the link between ADPKD and the early
      cardiovascular complications including hypertension. Secondly, we will describe
      the potential role of OS in the early stages of ADPKD and its possible importance
      beyond the chronic kidney disease (CKD) effect. Finally, we will discuss some
      pharmacological agents capable of reducing reactive oxygen species and OS, which
      might represent potential treatment targets for ADPKD.

PMID- 30105412
TI  - Amid proton transfer (APT) and magnetization transfer (MT) MRI contrasts provide
      complimentary assessment of brain tumors similarly to proton magnetic resonance
      spectroscopy imaging (MRSI).
AB  - OBJECTIVES: Using MRSI as comparison, we aimed to explore the difference between
      amide proton transfer (APT) MRI and conventional semi-solid magnetization
      transfer ratio (MTR) MRI, and to investigate if molecular APT and structural MTR
      can provide complimentary information in assessing brain tumors. METHODS:
      Seventeen brain tumor patients and 17 age- and gender-matched volunteers were
      included and scanned with anatomical MRI, APT and MT-weighted MRI, and MRSI.
      Multi-voxel choline (Cho) and N-acetylaspartic acid (NAA) signals were quantified
      from MRSI and compared with MTR and MTRasym(3.5ppm) contrasts averaged from
      corresponding voxels. Correlations between contrasts were explored voxel-by-voxel
      by pooling values from all voxels into Pearson's correlation analysis.
      Differences in correlation coefficients were tested with the Z-test (set at
      p<0.05). RESULTS: APT and MT provide good contrast and quantitative parameters in
      tumor imaging, as do the metabolite (Cho and NAA) maps. MTRasym(3.5ppm)
      significantly correlated with MTR (R=-0.61, p<0.0001), Cho (R=0.568, p<0.0001)
      and NAA (R=-0.619, p<0.0001) in tumors, and MTR also significantly correlated
      with Cho (R=-0.346, p<0.0001) and NAA (R=0.624, p<0.0001). In healthy volunteers,
      MTRasym(3.5ppm) was non-significantly correlated with MTR (R=-0.049, p=0.239),
      Cho (R=0.030, p=0.478) and NAA (R=-0.083, p=0.046). Significant correlations were
      found among MTR with Cho (R=0.199, p<0.0001) and NAA (R=0.263, p<0.0001) in the
      group of healthy volunteers with lower correlation R values than those in tumor
      patients. CONCLUSIONS: APT and MT could provide independent and supplementary
      information for the comprehensive assessment of molecular and structural changes
      due to brain tumor cancerogenesis. KEY POINTS: * MTR asym(3.5ppm) positively
      correlated with Cho while negatively with NAA in tumors. * MTR positively
      correlated with NAA while negatively with Cho in tumors. * Combining APT/MT
      provides molecular and structural information similarly to MRSI.

PMID- 30105414
TI  - Oxidative stress in chronic kidney disease.
AB  - Oxidative stress (OS), defined as disturbances in the pro-/antioxidant balance,
      is harmful to cells due to the excessive generation of highly reactive oxygen
      (ROS) and nitrogen (RNS) species. When the balance is not disturbed, OS has a
      role in physiological adaptations and signal transduction. However, an excessive
      amount of ROS and RNS results in the oxidation of biological molecules such as
      lipids, proteins, and DNA. Oxidative stress has been reported in kidney disease,
      due to both antioxidant depletions as well as increased ROS production. The
      kidney is a highly metabolic organ, rich in oxidation reactions in mitochondria,
      which makes it vulnerable to damage caused by OS, and several studies have shown
      that OS can accelerate kidney disease progression. Also, in patients at advanced
      stages of chronic kidney disease (CKD), increased OS is associated with
      complications such as hypertension, atherosclerosis, inflammation, and anemia. In
      this review, we aim to describe OS and its influence on CKD progression and its
      complications. We also discuss the potential role of various antioxidants and
      pharmacological agents, which may represent potential therapeutic targets to
      reduce OS in both pediatric and adult CKD patients.

PMID- 30105415
TI  - Time-averaged hemoglobin values, not hemoglobin cycling, have an impact on
      outcomes in pediatric dialysis patients.
AB  - BACKGROUND: During erythropoietin-stimulating agent (ESA) treatment, hemoglobin
      (Hb) levels usually fluctuate; this phenomenon is known as "Hb cycling (HC)." In
      this study, we aimed to evaluate the predictors of HC and its impact on left
      ventricular hypertrophy (LVH) as a patient-important outcome parameter in
      pediatric dialysis patients. METHODS: Records of patients followed up in nine
      pediatric nephrology centers between 2008 and 2013 were reviewed. More than 1
      g/dL decrease or increase in Hb level was considered as HC. Patients were divided
      into two groups according to 12-month Hb trajectory as rare cycling (RC) (<= 3)
      and frequent cycling (FC) (> 3 fluctuation) as well as three groups based on T-A
      Hb levels: < 10, 10-11, and > 11 g/dL. RESULTS: Two hundred forty-five dialysis
      (160 peritoneal dialysis (PD) and 85 hemodialysis (HD)) patients aged 12.3 +/-
      5.1 (range 0.5-21) years were enrolled in this study. Fifty-two percent of the
      patients had RC, 45% had FC, and only 3% had no cycling. There were no
      differences between HC groups with respect to age, dialysis modality, having
      anemia, hospitalization rate, residual urine volume, and mortality. Although left
      ventricular mass index (LVMI) tended to be higher in RC than FC group (65 +/- 37
      vs 52 +/- 23 g/m2.7, p = 0.056), prevalence of LVH was not different between the
      groups (p = 0.920). In regression analysis, FC was not a risk factor for LVH, but
      low T-A Hb level (< 10 g/dL) was a significant risk for LVH (OR = 0.414, 95% CI
      0.177-0.966, p = 0.04). The target Hb levels were more often achieved in PD
      patients, and the number of deaths was significantly lower in non-anemic patients
      (Hb level > 11 g/dL). CONCLUSION: Hb cycling is common among dialysis patients.
      Severity of anemia rather than its cycling has more significant impact on the
      prevalence of LVH and on inflammatory state.

PMID- 30105417
TI  - Rab27a Regulates Human Perivascular Adipose Progenitor Cell Differentiation.
AB  - PURPOSE: Perivascular adipose tissue (PVAT) surrounds blood vessels and regulates
      vascular tone through paracrine secretion of cytokines. During conditions
      promoting cardiometabolic dysfunction, such as obesity, cytokine secretion is
      altered towards a proinflammatory and proatherogenic profile. Despite the
      clinical implications for cardiovascular disease, studies addressing the biology
      of human PVAT remain limited. We are interested in characterizing the resident
      adipose progenitor cells (APCs) because of their potential role in PVAT expansion
      during obesity. We also focused on proteins regulating paracrine interactions,
      including the small GTPase Rab27a, which regulates protein trafficking and
      secretion. METHODS: PVAT from the ascending aorta was collected from patients
      with severe cardiovascular disease undergoing coronary artery bypass grafting
      (CABG). Freshly-isolated PVAT was digested and APC expanded in culture for
      characterizing progenitor markers, evaluating adipogenic potential and assessing
      the function(s) of Rab27a. RESULTS: Using flow cytometry, RT-PCR, and immunoblot,
      we characterized APC from human PVAT as negative for CD45 and CD31 and expressing
      CD73, CD105, and CD140A. These APCs differentiate into multilocular, UCP1
      producing adipocytes in vitro. Rab27a was detected in interstitial cells of human
      PVAT in vivo and along F-actin tracks of PVAT-APC in vitro. Knockdown of Rab27a
      using siRNA in PVAT-APC prior to induction resulted in a marked reduction in
      lipid accumulation and reduced expression of adipogenic differentiation markers.
      CONCLUSIONS: PVAT-APC from CABG donors express common adipocyte progenitor
      markers and differentiate into UCP1-containing adipocytes. Rab27a has an
      endogenous role in promoting the maturation of adipocytes from human PVAT-derived
      APC.

PMID- 30105416
TI  - Hypoxemia in the ICU: prevalence, treatment, and outcome.
AB  - BACKGROUND: Information is limited regarding the prevalence, management, and
      outcome of hypoxemia among intensive care unit (ICU) patients. We assessed the
      prevalence and severity of hypoxemia in ICU patients and analyzed the management
      and outcomes of hypoxemic patients. METHODS: This is a multinational,
      multicenter, 1-day point prevalence study in 117 ICUs during the spring of 2016.
      All patients hospitalized in an ICU on the day of the study could be enrolled.
      Hypoxemia was defined as a PaO2/FiO2 ratio <= 300 mmHg and classified as mild
      (PaO2/FiO2 between 300 and 201), moderate (PaO2/FiO2 between 200 and 101), and
      severe (PaO2/FiO2 <= 100 mmHg). RESULTS: Of 1604 patients included, 859 (54%, 95%
      CI 51-56%) were hypoxemic, 51% with mild (n = 440), 40% with moderate (n = 345),
      and 9% (n = 74) with severe hypoxemia. Among hypoxemic patients, 61% (n = 525)
      were treated with invasive ventilation, 10% (n = 84) with non-invasive
      ventilation, 5% (n = 45) with high-flow oxygen therapy, 22% (n = 191) with
      standard oxygen, and 1.6% (n = 14) did not receive oxygen. Protective ventilation
      was widely used in invasively ventilated patients. Twenty-one percent of
      hypoxemic patients (n = 178) met criteria for acute respiratory distress syndrome
      (ARDS) including 65 patients (37%) with mild, 82 (46%) with moderate, and 31
      (17%) with severe ARDS. ICU mortality was 27% in hypoxemic patients and
      significantly differed according to severity: 21% in mild, 26% in moderate, and
      50% in patients with severe hypoxemia, p < 0.001. Multivariate Cox regression
      identified moderate and severe hypoxemia as independent factors of ICU mortality
      compared to mild hypoxemia (adjusted hazard ratio 1.38 [1.00-1.90] and 2.65 [1.69
      4.15], respectively). CONCLUSIONS: Hypoxemia affected more than half of ICU
      patients in this 1-day point prevalence study, but only 21% of patients had ARDS
      criteria. Severity of hypoxemia was an independent risk factor of mortality among
      hypoxemic patients. Trial registration NCT 02722031.

PMID- 30105418
TI  - Initial application of three-dimensional speckle-tracking echocardiography to
      detect subclinical left ventricular dysfunction and stratify cardiomyopathy
      associated with Duchenne muscular dystrophy in children.
AB  - Three-dimensional (3D) speckle-tracking echocardiography (STE) is a new imaging
      modality used for quantitative analysis of left ventricular (LV) function. The
      aim of this study is to assess the value of 3D STE in early detection of
      subclinical myocardial involvement in children with Duchenne muscular dystrophy
      (DMD). Fifty-six children with DMD (mean age, 8.8 +/- 1.9 years) and 31 age
      matched control subjects were studied. Patients were subdivided into two groups
      by age: <= 8 or > 8 years. Standard echocardiography examinations were performed
      to measure LV size and ejection fraction (EF). 3D STE was performed to assess LV
      3D global strain and LV end-diastolic volume (EDV), end-systolic volume (ESV),
      and EF. Standard and 3D echocardiography measures were compared between children
      with DMD and those in the control group as well as between different patient
      groups. The areas under the receiver-operating characteristic (ROC) curve were
      calculated to determine the capability of 3D global strain indices to
      discriminate between patients and control subjects. No significant difference was
      detected in either LVEF derived from M-mode or 3D echocardiography between the
      two groups, and they were both within the normal range. Compared with control
      subjects, children with DMD had significantly reduced LV 3D global longitudinal
      strain (GLS; - 16.6 +/- 4.7 vs. - 19.5 +/- 3.7, p = 0.003), global
      circumferential strain (GCS; - 13.7 +/- 2.9 vs. - 15.8 +/- 2.6, p = 0.001),
      global radial strain (GRS; 42.5 +/- 9.7 vs. 50.3 +/- 10.4, p = 0.001), and global
      area strain (GAS; - 25.3 +/- 4.9 vs. - 30.7 +/- 4.1, p = 0.000). The older DMD
      children (age > 8 years) had lower GLS (- 15.1 +/- 4.43 vs. - 18.6 +/- 4.35, p <
      0.05), GCS (- 12.8 +/- 3.48 vs. - 14.8 +/- 2.83, p < 0.001), GAS (- 23.8 +/- 4.7
      vs. - 29.0 +/- 5.4, p < 0.001), and GRS (40.7 +/- 8.8 vs. 47.3 +/- 11.5, p <
      0.05) than younger patients (age <= 8 years). The AUC of GAS was 0.80, and the
      cutoff value of - 29.5 had a sensitivity of 85.7% and a specificity of 71.0% for
      differentiating DMD patients from control. 3D speckle-tracking echocardiography
      is useful for detecting subclinical myocardial dysfunction and stratifying
      cardiomyopathy in children with DMD.

PMID- 30105421
TI  - Applications of Reactive Cysteine Profiling.
AB  - Cysteine thiols are involved in a diverse set of biological transformations,
      including nucleophilic and redox catalysis, metal coordination and formation of
      both dynamic and structural disulfides. Often posttranslationally modified,
      cysteines are also frequently alkylated by electrophilic compounds, including
      electrophilic metabolites, drugs, and natural products, and are attractive sites
      for covalent probe and drug development. Quantitative proteomics combined with
      activity-based protein profiling has been applied to annotate cysteine
      reactivity, susceptibility to posttranslational modifications, and accessibility
      to chemical probes, uncovering thousands of functional and small-molecule
      targetable cysteines across a diverse set of proteins, proteome-wide in an
      unbiased manner. Reactive cysteines have been targeted by high-throughput
      screening and fragment-based ligand discovery efforts. New cysteine-reactive
      electrophiles and compound libraries have been synthesized to enable inhibitor
      discovery broadly and to minimize nonspecific toxicity and off-target activity of
      compounds. With the recent blockbuster success of several covalent inhibitors,
      and the development of new chemical proteomic strategies to broadly identify
      reactive, ligandable and posttranslationally modified cysteines, cysteine
      profiling is poised to enable the development of new potent and selective
      chemical probes and even, in some cases, new drugs.

PMID- 30105420
TI  - Role of Exosomes as a Treatment and Potential Biomarker for Stroke.
AB  - Approximately, 16 million strokes occur worldwide each year, causing 6 million
      deaths and considerable disability, implying an enormous social, individual
      health, and economic burden. Due to this high incidence, strategies to promote
      stroke recovery are urgently needed. Research into new therapeutic approaches for
      stroke has determined that intravenous administration of mesenchymal stem cells
      (MSCs) is a good strategy to improve recovery by amplifying mechanisms implicated
      in brain plasticity. Recent studies have demonstrated the efficacy of MSCs in
      stroke, with no need for them to reach the area of brain injury. Although the
      mechanisms by which they mediate restorative effects are still unknown, the
      evidence suggests that MSCs might use specialised communication by sending and
      receiving biological information included in elements called exosomes. Exosomes
      are nanosized extracellular vesicles released into physical environments, and
      they have recently been suggested to mediate restorative stem cell effects.
      Moreover, after stroke, exosomes can also be synthesised and released from brain
      cells, passing through the blood-brain barrier (BBB), and can be detected in
      peripheral blood or in cerebrospinal fluid. Thus, exosomes could possibly be
      biomarkers that reflect pathological progress and promote stroke recovery. This
      review discusses the translational aspects of MSC-derived exosomes and their
      various roles in brain repair and as circulating biomarkers in stroke.

PMID- 30105419
TI  - Ultrasonography of traumatic injuries to limb peripheral nerves: technical
      aspects and spectrum of features.
AB  - Traumatic injury to limb peripheral nerves represents an important cause of
      morbidity and disability. Timely diagnosis and treatment are crucial to
      optimizing outcomes. The initial evaluation requires a careful history, a
      thorough physical examination, and electrodiagnostic tests, which lead in most
      cases to a diagnostic suspicion, but fail to provide an extensive qualitative and
      quantitative assessment of the nerve damage. Ultrasonography (US) is a low-cost,
      non-invasive technique which allows for direct visualization of nerve internal
      structure. It enables performing dynamic examinations and nerves can be followed
      over long distances in a limb in relatively short times, adding paramount
      information to extensively characterize the specific type of lesion, and to plan
      the appropriate treatment. Magnetic resonance imaging (MRI) is complementary to
      US, especially in examining deep-seated and proximal nerve segments, but is
      expensive, not available in all institutions and less accepted by patients. The
      purpose of this review is to describe the role of ultrasonography in the setting
      of traumatic injury to peripheral nerves, analyzing the main US features in
      specific types of trauma. Technical aspects with key considerations for
      optimization are discussed. A brief comparative evaluation between US and MRI is
      also provided.

PMID- 30105422
TI  - Residual Immune Activation and Latency.
AB  - The introduction of combination antiretroviral therapy (cART) in the 1990s has
      dramatically changed the course of HIV infection, decreasing the risk for both
      AIDS- and non-AIDS-related events. Cancers, cardiovascular disease (CVD), liver
      and kidney disease, neurological disorders and frailty have become of great
      importance lately in the clinical management as they represent the principal
      cause of death in people living with HIV who receive cART (Kirk et al. in Clin
      Infect Dis 45(1):103-10, 2007; Strategies for Management of Antiretroviral
      Therapy Study et al. N Engl J Med 355(22):2283-2296, 2006; Ances et al. J Infect
      Dis 201(3):336-340, 2010; Desquilbet et al. J Gerontol A Biol Sci Med Sci
      62(11):1279-1286, 2007; Lifson et al. HIV Clin Trials 9(3):177-185, 2008).
      Despite the undeniable achievements of cART, we are now faced with its
      limitations: a considerable proportion of individuals, referred as to
      immunological non-responders, fails to reconstitute the immune system despite
      optimal treatment and viral suppression (Kelley et al. Clin Infect Dis 48(6):787
      794, 2009; Robbins et al. Clin Infect Dis 48(3):350-361, 2009) and remains at
      high risk for opportunistic infections and non-AIDS-related events (Strategies
      for Management of Antiretroviral Therapy Study et al. N Engl J Med 355(22):2283
      2296, 2006). Moreover, the generalized state of immune activation and
      inflammation, linked to serious non-AIDS events, persists despite successful HIV
      suppression with cART. Finally, the current strategies have so far failed to
      eradicate the virus, and inflammation appears a driving force in viral
      persistence. In the light of all this, it is of fundamental importance to
      investigate the pathophysiological processes that link incomplete immune
      recovery, immune activation and HIV persistence to design targeted therapies that
      could impact on the three.

PMID- 30105423
TI  - Target Identification of Bioactive Covalently Acting Natural Products.
AB  - There are countless natural products that have been isolated from microbes,
      plants, and other living organisms that have been shown to possess therapeutic
      activities such as antimicrobial, anticancer, or anti-inflammatory effects.
      However, developing these bioactive natural products into drugs has remained
      challenging in part because of their difficulty in isolation, synthesis,
      mechanistic understanding, and off-target effects. Among the large pool of
      bioactive natural products lies classes of compounds that contain potential
      reactive electrophilic centers that can covalently react with nucleophilic amino
      acid hotspots on proteins and other biological molecules to modulate their
      biological action. Covalently acting natural products are more amenable to rapid
      target identification and mapping of specific druggable hotspots within proteins
      using activity-based protein profiling (ABPP)-based chemoproteomic strategies. In
      addition, the granular biochemical insights afforded by knowing specific sites of
      protein modifications of covalently acting natural products enable the
      pharmacological interrogation of these sites with more synthetically tractable
      covalently acting small molecules whose structures are more easily tuned. Both
      discovering binding pockets and targets hit by natural products and exploiting
      druggable modalities targeted by natural products with simpler molecules may
      overcome some of the challenges faced with translating natural products into
      drugs.

PMID- 30105424
TI  - Activity-Based Protein Profiling for the Study of Parasite Biology.
AB  - Parasites exist within most ecological niches, often transitioning through
      biologically and chemically complex host environments over the course of their
      parasitic life cycles. While the development of technologies for genetic
      engineering has revolutionised the field of functional genomics, parasites have
      historically been less amenable to such modification. In light of this,
      parasitologists have often been at the forefront of adopting new small-molecule
      technologies, repurposing drugs into biological tools and probes. Over the last
      decade, activity-based protein profiling (ABPP) has evolved into a powerful and
      versatile chemical proteomic platform for characterising the function of enzymes.
      Central to ABPP is the use of activity-based probes (ABPs), which covalently
      modify the active sites of enzyme classes ranging from serine hydrolases to
      glycosidases. The application of ABPP to cellular systems has contributed vastly
      to our knowledge on the fundamental biology of a diverse range of organisms and
      has facilitated the identification of potential drug targets in many pathogens.
      In this chapter, we provide a comprehensive review on the different forms of ABPP
      that have been successfully applied to parasite systems, and highlight key
      biological insights that have been enabled through their application.

PMID- 30105425
TI  - Two-step verification of brain tumor segmentation using watershed-matching
      algorithm.
AB  - Though the modern medical imaging research is advancing at a booming rate, it is
      still a very challenging task to detect brain tumor perfectly. Medical imaging
      unlike other imaging system has highest penalty for a minimal error. So, the
      detection of tumor should be accurate to minimize the error. Past researchers
      used biopsy to detect the tumor tissue from the other soft tissues in the brain
      which is time-consuming and may have errors. We outlined a two-stage verification
      based tumor segmentation that makes the detection more accurate. We segmented the
      tumor area from the MR image and then used another algorithm to match the
      segmented portion with the ground truth image. We named this new algorithm as
      watershed-matching algorithm. The most promising part of our model is the status
      checking of the tumor by finding the area of the tumor. Our proposed model works
      better than other state-of-the art works on BRATS 2017 dataset.

PMID- 30105426
TI  - Precision Medicine: Familiarity, Perceived Health Drivers, and Genetic Testing
      Considerations Across Health Literacy Levels in a Diverse Sample.
AB  - A clear awareness of a patient's knowledge, values, and perspectives is an
      important component of effective genetic counseling. Advances in precision
      medicine, however, have outpaced our understanding of patient perceptions of this
      new approach. Patient views may differ across the three domains of precision
      medicine (genetics, behavioral, and environmental determinants of health),
      ethnic/racial groups, and health literacy levels. This study describes and
      compares group differences in familiarity, perceptions, and preferences for
      precision medicine in a diverse sample. Between 2016 and 2017, 252 participants
      completed a 10-15-min survey in three primary care clinics in Florida and
      Tennessee. The final sample was 42.5% African American/Black, 25.8%
      Hispanic/Latino, 25.0% White, and 6.7% other ethnicity/race. Less than a quarter
      of participants reported being familiar with the term "precision medicine," but
      were more familiar with basic genetic terms. Participants with higher health
      literacy reported greater familiarity with terms (p <= .003). African
      Americans/Black participants were more likely to identify ethnicity/race and
      discrimination as influencing their health (p <= .004). When deciding to get a
      genetic test, individuals across ethnic/racial groups shared similar
      considerations. Those with higher health literacy, however, gave significantly
      greater importance to provider trust (p <= .008). Given the recent emergence of
      precision medicine, at present there may be limited differences in patient
      perceptions across ethnic/racial groups. Culturally sensitive efforts, tailored
      to health literacy level, may aid equitable precision medicine uptake.

PMID- 30105427
TI  - "First-degree AV block-a benign entity?" Insertable cardiac monitor in patients
      with 1st-degree AV block reveals presence or progression to higher grade block or
      bradycardia requiring pacemaker implant.
AB  - BACKGROUND: First-degree AV block has in the past generally been considered a
      benign condition. A few recent studies have shown that 1st-degree AV block is
      associated with an increased risk for heart failure, pacemaker (IPG)
      implantation, and death. We investigated the outcomes of patients who received an
      insertable cardiac monitor (ICM) (Medtronic Reveal XT(r)) within the scope of the
      INSIGHT XT study and had 1st-degree AV block at baseline. METHODS: The
      observational, international, multi-center INSIGHT (R)XT study prospectively
      enrolled 1003 patients implanted with an ICM for arrhythmia diagnosis,
      irrespective of the clinical indication. This analysis includes 37 patients who
      had documented 1st-degree AV block at enrolment. Patients with known concurrent
      higher grade block at enrolment were excluded. RESULTS: The indications for
      rhythm monitoring and ICM implantation were syncope/pre-syncope in 54.1%,
      cryptogenic stroke in 18.9%, AF with rhythm control intervention in 21.6%, and
      unexplained palpitations in 5.4%. Mean age was 68 +/- 14 years, 75.7% were male,
      and concurrent bundle branch block was present in 8.1%. The median follow-up time
      was 12.2 months (IQR3.9-15.9). Fifteen patients (40.5%) received an IPG during
      the follow-up, and in 93.3% of the cases, the implant was needed to treat a now
      detected more severe bradycardia or progression of the conduction disease.
      CONCLUSIONS: ICM either revealed progression of 1st-degree AV block to a higher
      grade block (53%) or detected an already existing more severe bradycardia
      warranting an IPG in 40.5% patients. This finding supports the conclusion that
      1st-degree AV block might be a risk marker for more severe intermittent
      conduction disease and is not benign in all patients. Further studies may reveal
      patient subgroups which are at risk for demonstrating or developing higher grade
      AV block and may warrant a future IPG implantation.

PMID- 30105428
TI  - The learning curve associated with the implantation of the Nanostim leadless
      pacemaker.
AB  - PURPOSE: Use of novel medical technologies, such as leadless pacemaker (LP)
      therapy, may be subjected to a learning curve effect. The objective of the
      current study was to assess the impact of operators' experience on the occurrence
      of serious adverse device effects (SADE) and procedural efficiency. METHODS:
      Patients implanted with a Nanostim LP (Abbott, USA) within two prospective
      studies (i.e., LEADLESS ll IDE and Leadless Observational Study) were assessed.
      Patients were categorized into quartiles based on operator experience. Learning
      curve analysis included the comparison of SADE rates at 30 days post-implant per
      quartile and between patients in quartile 4 (> 10 implants) and patients in
      quartiles 1 through 3 (1-10 implants). Procedural efficiency was assessed based
      on procedure duration and repositioning attempts. RESULTS: Nanostim LP implant
      was performed in 1439 patients by 171 implanters at 60 centers in 10 countries. A
      total of 91 (6.4%) patients experienced a SADE in the first 30 days. SADE rates
      dropped from 7.4 to 4.5% (p = 0.038) after more than 10 implants per operator.
      Total procedure duration decreased from 30.9 +/- 19.1 min in quartile 1 to 21.6
      +/- 13.2 min (p < 0.001) in quartile 4. The need for multiple repositionings
      during the LP procedure reduced in quartile 4 (14.8%), compared to quartiles 1
      (26.8%; p < 0.001), 2 (26.6%; p < 0.001), and 3 (20.4%; p = 0.03). CONCLUSIONS:
      Learning curves exist for Nanostim LP implantation. Procedure efficiency improved
      with increased operator experience, according to a decrease in the incidence of
      SADE, procedure duration, and repositioning attempts.

PMID- 30105429
TI  - His bundle pacing.
AB  - His bundle pacing (HBP) has recently emerged as a technique to avoid the negative
      effects of long-term right ventricular apical pacing. In addition to providing
      physiologic ventricular activation, HBP has been shown to correct underlying
      conduction abnormalities in certain patients. Although large prospective,
      randomized clinical trials have not yet been completed, the available
      observational clinical data support the safety and efficacy of this technique.
      Here, we review the physiology of the his bundle (HB) as it relates to HBP,
      describe the current clinical experience, and discuss future directions of this
      emerging therapy.

PMID- 30105430
TI  - The Biological Mechanisms of Action of Cardiac Progenitor Cell Therapy.
AB  - PURPOSE OF REVIEW: Cell therapy for cardiovascular diseases is regarded as a
      rapidly growing field within regenerative medicine. Different cellular
      populations enriched for cardiac progenitor cells (CPCs), or derivate a-cellular
      products, are currently under preclinical and clinical evaluation. Here, we have
      reviewed the described mechanisms whereby resident post-natal CPCs, isolated in
      different ways, act as a therapeutic product on the damaged myocardium. RECENT
      FINDINGS: Several biological mechanisms of action have been described which can
      explain the multiple therapeutic effects of CPC treatment observed on cardiac
      function and remodelling. These mechanisms span from direct cardiovascular
      differentiation, through induction of resident progenitor proliferation, to
      paracrine effects on cardiac and non-cardiac cells mediated by exosomes and non
      coding RNAs. All the reported mechanisms of action support an integrated view
      including cardiomyogenesis, cardioprotection, and anti-fibrotic effects.
      Moreover, future developments of CPC therapy approaches may support cell-free
      strategies, exploiting effective pleiotropic cell-derived products, such as
      exosomes.

PMID- 30105431
TI  - Safety and efficiency of ultrasound-guided low power microwave ablation in the
      treatment of cervical metastatic lymph node from papillary thyroid carcinoma: a
      mean of 32 months follow-up study.
AB  - PURPOSE: To evaluate the safety and efficiency of microwave ablation (MWA) with
      low power of 20 w, respectively, in the treatment of cervical metastatic lymph
      node (CMLN) from papillary thyroid carcinoma (PTC) with a mean of 32-month follow
      up. METHODS: Eleven patients in total with 24 cervical lymph nodes (LNs)
      diagnosed with CMLN from PTC underwent MWA at a power of 20 w. We recorded images
      of the LNs under ultrasound first before MWA and 1, 3, 6, 12, months after MWA,
      and then every 6 months, respectively. The volumes of the LNs were compared
      before MWA and at each follow-up point after MWA. The thyroglobulin (Tg) test was
      performed before MWA and 3 months after MWA. RESULTS: All patients were
      successfully treated, and they showed no major complications. Before MWA, the
      mean volume of the LNs was 364.15 +/- 306.89 mm3, which decreased to 234.10 +/-
      230.34 mm3, 107.51 +/- 129.47 mm3, 20.88 +/- 39.27 mm3, 3.38 +/- 12.74 mm3, and
      completely disappeared at the follow-up point of 1, 3, 6, 12, and 18 months after
      MWA, respectively. The mean Tg was 11.81 +/- 7.50 ng/ml, a data significantly
      decreased to 0.43 +/- 0.11 ng/ml 3 months after MWA (P = 0.000). In the follow-up
      period, no recurrent lesions were found. CONCLUSIONS: For the treatment of CMLN
      from PTC, low power MWA showed good safety and efficacy. MWA is likely to be a
      candidate for patients with high risks or who refuse reoperation.

PMID- 30105432
TI  - High Doses of Copper and Mercury Changed Cecal Microbiota in Female Mice.
AB  - The aim of the present study was to investigate the effects of high doses of
      copper (Cu) and mercury (Hg) on the cecal microbiota in female mice. Forty-eight
      Kunming mice were randomly divided into the control group (CCk group), the Cu
      group (CCu group), the Hg group (CHg group), and the Cu + Hg group (CCH group).
      At the 90th day, cecal tissues were prepared for histopathological analysis and
      cecal contents for analysis by 16S rRNA sequencing method. Cecal tissues from
      treatment groups had histopathological lesions including increased thickness of
      inner muscularis and outer muscularis, widened submucosa, decreased goblet cells,
      mild to moderate necrosis of enterocytes, blunting of intestinal villi, and
      severe atrophy of central lacteal. Furthermore, compared to the CCk group, the
      abundance of bacteria genera Rikenella, Jeotgailcoccus, and Staphylococcus were
      significantly decreased, whereas the bacteria genus Corynebacterium was
      significantly increased in the CCu group. The abundance of bacteria genera of
      Sporosarcina, Jeotgailcoccus, and Staphylococcus were significantly decreased in
      the CHg group and CCH group. The bacteria genus Anaeroplasma was significantly
      increased in the CCH group. The results indicated that high doses of Cu and Hg
      caused histopathological lesions and changed the diversity of microbiota in the
      cecum of female mice, which provide a theoretical basis for more accurate
      assessment of the risk in intestinal diseases caused by Cu and Hg.

PMID- 30105434
TI  - Should we ever stop clinical trials for efficacy?

PMID- 30105433
TI  - Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS): an
      international expert consensus initiative for improvement of animal modeling in
      sepsis.
AB  - PURPOSE: Pre-clinical animal studies precede the majority of clinical trials.
      While the clinical sepsis definitions and recommended treatments are regularly
      updated, a systematic review of pre-clinical models of sepsis has not been done
      and clear modeling guidelines are lacking. To address this deficit, a Wiggers
      Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May,
      2017. The conference goal was to identify limitations of pre-clinical sepsis
      models and to propose a set of guidelines, defined as the "Minimum Quality
      Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational
      value of these models. METHODS: 31 experts from 13 countries participated and
      were divided into 6 thematic Working Groups (WG): (1) Study Design, (2) Humane
      modeling, (3) Infection types, (4) Organ failure/dysfunction, (5) Fluid
      resuscitation and (6) Antimicrobial therapy endpoints. As basis for the MQTiPSS
      discussions, the participants conducted a literature review of the 260 most
      highly cited scientific articles on sepsis models (2002-2013). RESULTS: Overall,
      the participants reached consensus on 29 points; 20 at "recommendation" (R) and 9
      at "consideration" (C) strength. This Executive Summary provides a synopsis of
      the MQTiPSS consensus (Tables 1, 2 and 3). CONCLUSIONS: We believe that these
      recommendations and considerations will serve to bring a level of standardization
      to pre-clinical models of sepsis and ultimately improve translation of pre
      clinical findings. These guideline points are proposed as "best practices" that
      should be implemented for animal sepsis models. In order to encourage its wide
      dissemination, this article is freely accessible in Shock, Infection and
      Intensive Care Medicine Experimental.

PMID- 30105435
TI  - In reply: Should we ever stop clinical trials for efficacy?

PMID- 30105436
TI  - Intraoperative Imaging with a Portable Gamma Camera May Reduce the False-Negative
      Rate for Melanoma Sentinel Lymph Node Surgery.
AB  - BACKGROUND: Preoperative imaging and intraoperative gamma probe (GP) localization
      is standard for identifying sentinel lymph nodes (SLNs) in melanoma patients. The
      aim of this prospective Institutional Review Board-approved study was to
      investigate whether an intraoperative portable gamma camera (PGC) improves SLN
      detection over the GP. METHODS: Lymphoscintigraphy and single photon emission
      computed tomography/computed tomography were performed after injection of 99mTc
      Tilmanocept in melanoma patients (>= 18 years, Breslow thickness >= 1.0 mm). A GP
      was used to localize the SLNs in each basin, which was explored by the GP to
      ensure that the operative field was < 10% counts of the hottest SLN. The PGC was
      then used after a negative GP screening. Any residual hotspots identified by the
      PGC were considered as additional SLNs and were removed following the 10% rule.
      RESULTS: Preoperative imaging of 100 patients identified 138 SLN basins, with 306
      SLNs being identified by conventional surgery. The PGC localized 89 additional
      SLNs in 54 patients. Thus, the PGC identified an additional 23% of SLNs [95%
      confidence interval (CI) 18-27%]. Four of these 89 SLNs showed micrometastasis in
      four patients, in two of whom the only tumor-positive SLN was identified by the
      PGC, preventing two false-negative cases. Thus, the null hypothesis that the PGC
      did not detect additional positive SLNs was rejected (p = 0.000). The overall SLN
      positive rate was 9.9% (39/395, 95% CI 6-12), and the overall patient positive
      rate was increased using the PGC, from 25 to 27% (27/100). CONCLUSIONS:
      Intraoperative PGC imaging yielded additional SLNs in a significant number of
      patients over GP alone. Identification of these additional SLNs resulted in
      upstaging of four patients with two patients being converted from a negative to a
      positive status, thus, preventing two false-negative cases.

PMID- 30105437
TI  - Correction to: Melanoma Staging: American Joint Committee on Cancer (AJCC) 8th
      Edition and Beyond.
AB  - In the original article, there were errors in Fig. 1a. Following is the corrected
      figure.

PMID- 30105439
TI  - Minority Race Predicts Treatment by Non-gynecologic Oncologists in Women with
      Gynecologic Cancer.
AB  - BACKGROUND: Outcomes of women with gynecologic cancer are superior when treated
      by gynecologic oncologists. The National Surgical Quality Improvement Program
      (NSQIP) began identifying gynecologic surgeon subspecialty in 2014. We sought to
      identify characteristics and outcomes of women treated by general gynecologists
      in comparison with women treated by gynecologic oncologists. PATIENTS AND
      METHODS: Patients undergoing hysterectomy for gynecologic malignancy in 2014 and
      2015 were abstracted from the NSQIP database. Patient characteristics,
      morbidities, surgeon specialty, and operative outcomes were captured. RESULTS:
      7271 hysterectomies were performed for malignant disease, and 669 were performed
      by generalists. In comparison with generalists, gynecologic oncologists operated
      on patients who were older (P < 0.001), more likely to be White [odds ratio (OR)
      2.1, P < 0.001], had disseminated cancer (OR 3.1, P < 0.001), had ascites (OR
      2.6, P < 0.001), and were classified as American Society of Anesthesiologists
      (ASA) class >= 3 (OR 1.7, P < 0.001). Gynecologic oncologists were also more
      likely to have hospital readmissions (OR 1.7, P = 0.004) and perform lymph node
      dissections for endometrial cancer (OR 2.2, P < 0.001). On multivariable
      analysis, older age [adjusted OR (aOR) 1.0, P = 0.021], White race (aOR 2.0, P <
      0.001), presence of disseminated cancer (aOR 2.5, P < 0.001), presence of ascites
      (aOR 1.8, P = 0.036), and ASA class >= 3 (aOR 1.6, P < 0.001) remained
      independent predictive factors for having a gynecologic oncology surgeon.
      CONCLUSIONS: The majority of gynecologic cancer cases are performed by
      gynecologic oncologists. Generalists are more likely to operate on minority
      patients and patients with fewer comorbidities. Further efforts to ensure access
      to specialized cancer care for all patients are needed.

PMID- 30105440
TI  - Hypoxia-Induced PLOD2 is a Key Regulator in Epithelial-Mesenchymal Transition and
      Chemoresistance in Biliary Tract Cancer.
AB  - BACKGROUND: The prognosis of biliary tract cancer (BTC) is unfavorable due to its
      chemoresistance. Hypoxia triggers epithelial-to-mesenchymal transition (EMT),
      which is closely related to drug resistance. In this study, we focused on the
      functional roles of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a
      hypoxia-induced gene, in BTC, and assessed the clinical significance of PLOD2.
      METHODS: The expression of PLOD2 under hypoxia was assessed in BTC cell lines.
      Gemcitabine-resistant (GR) BTC cell lines were transfected with small interfering
      RNA (siRNA) against PLOD2, and EMT markers and chemoresistance were evaluated.
      PLOD2 expression was also characterized using immunohistochemistry in BTC
      clinical specimens following resection. Patient survival was analyzed and the
      role of PLOD2 expression was examined. RESULTS: The expression of PLOD2 was
      induced by hypoxia in vitro and was upregulated in BTC-GR cell lines, which had
      low expression of epithelial markers and high expression of mesenchymal markers.
      Downregulation of PLOD2 by siRNA resulted in improved chemoresistance, recovery
      of epithelial markers, and reduction of mesenchymal markers. In the resected BTC
      samples, PLOD2 expression was significantly correlated with lymph node metastasis
      (p = 0.037) and stage (p = 0.001). Recurrence-free survival (p = 0.011) and
      overall survival (p < 0.001) rates were significantly lower in patients with high
      expression of PLOD2. PLOD2 expression was an independent prognostic factor for
      overall survival (p = 0.019). CONCLUSIONS: The expression of PLOD2 influenced
      chemoresistance through EMT, and high expression of PLOD2 was a significant
      unfavorable prognostic factor in BTC patients. PLOD2 might be a potential
      therapeutic target for overcoming chemoresistance.

PMID- 30105441
TI  - Evaluation of the IncoStress device for urinary incontinence: a feasibility study
      and pilot randomised controlled trial.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the feasibility
      of recruitment to and outcomes from a pilot randomised study of the IncoStress
      device as an adjunct to conservative treatment for urinary incontinence. METHODS:
      Women with urinary incontinence were randomised on a 2:1 basis to usual care
      (control) or usual care plus use of the IncoStress device (intervention). Process
      outcomes (retention and compliance) were recorded plus symptom outcomes (IQOL and
      ICIQ-FLUTS questionnaires). A sample of participants took part in an interview to
      understand the frequency of use of the device and satisfaction. RESULTS: Eighty
      women (51 intervention, 29 control) were recruited. Follow-up responses were
      obtained from 34 intervention group (66.7%) and 17 (58.6%) control patients.
      Women used the device for a median 3 days a week (0-7), 18 out of 34 (53%) found
      it easy to use and 21 (61.8%) were satisfied with the device. Median IQOL score
      in the intervention group improved from a baseline of 42.4 (0-94) to 68.2 (5-98)
      at follow-up and in the control group from 45.5 (0-88) to 53.0 (0-94). Median
      ICIQ-FLUTS score in the intervention group improved from 14.5 (6-35) to 12.5 (4
      26) and in the control group from 15.0 (5-35) to 14.0 (6-38). CONCLUSIONS:
      Recruitment and randomisation were feasible and robust. This study demonstrates
      that a large-scale RCT is feasible and the IncoStress has potential value.

PMID- 30105438
TI  - Proposal for a Risk-Based Categorization of Uterine Carcinosarcoma.
AB  - PURPOSE: To propose a categorization model of uterine carcinosarcoma (UCS) based
      on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. METHODS: This
      secondary analysis of a prior multicenter retrospective study examined 889 cases
      of UCS with available histologic evaluation. Based on survival outcome, cases
      were clustered into three groups: low-grade carcinoma with nondominant homologous
      sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous
      sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant
      homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with
      heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor
      characteristics and outcome were examined based on the categorization. RESULTS:
      Women in type C category were more likely to be older, obese, and Caucasian,
      whereas those in type A category were younger, less obese, Asian, and nulligravid
      (all P < 0.01). Type C tumors were more likely to have metastatic implants, large
      tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph
      node ratio, whereas type A tumors were more likely to be early-stage disease and
      small (all P < 0.05). On multivariate analysis, tumor categorization was
      independently associated with progression-free survival (5-year rates: 70.1% for
      type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause
      specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1%
      for type C, adjusted P < 0.01). CONCLUSION: Characteristic differences in
      clinicopathological factors and outcomes in UCS imply that different underlying
      etiologies and biological behaviors may be present, supporting a new
      classification system.

PMID- 30105443
TI  - Evaluation of supplemental samples in longitudinal research with non-normal
      missing data.
AB  - Missing data is a commonly encountered problem in longitudinal research.
      Methodological articles provide advice on ways to handle missing data at the
      analysis stage, however, there is less guidance for researchers who wish to use
      supplemental samples (i.e., the addition of new participants to the original
      sample after missing data appear at the second or later measurement occasions) to
      handle attrition. The purpose of this study is to evaluate the effects of using
      supplemental samples when analyzing longitudinal data that are non-normally
      distributed. We distinguish between two supplemental approaches: a refreshment
      approach where researchers select additional participants using the same criteria
      as the initial participants (i.e., random selection from the population of
      interest) and a replacement approach where researchers identify auxiliary
      variables that explain missingness and select new participants based on those
      attributes. Overall, simulation results suggest that the addition of refreshment
      samples, but not replacement samples, is an effective way to respond to attrition
      in longitudinal research. Indeed, use of refreshment samples may reduce bias of
      parameter estimates and increase efficiency and statistical power, whereas use of
      replacement samples results in biased parameter estimates. Our findings may be
      utilized by researchers considering using supplemental samples and provide
      guidance for selecting an appropriate supplemental sample approach.

PMID- 30105442
TI  - Argus: An open-source and flexible software application for automated
      quantification of behavior during social interaction in adult zebrafish.
AB  - Zebrafish show great potential for behavioral neuroscience. Promising lines of
      research, however, require the development and validation of software tools that
      will allow automated and cost-effective behavioral analysis. Building on our
      previous work with the RealFishTracker (in-house-developed tracking system), we
      present Argus, a data extraction and analysis tool built in the open-source R
      language for behavioral researchers without any expertise in R. Argus includes a
      new, user-friendly, and efficient graphical user interface, instead of a command
      line interface, and offers simplicity and flexibility in measuring complex
      zebrafish behavior through customizable parameters. In this article, we compare
      Argus with Noldus EthoVision and Noldus The Observer, to validate this new
      system. All three software applications were originally designed to quantify the
      behavior of a single subject. We first also performed an analysis of the movement
      of individual fish and compared the performance of the three software
      applications. Next we computed and quantified the behavioral variables that
      characterize dyadic interactions between zebrafish. We found that Argus and
      EthoVision extract similar absolute values and patterns of changes in these
      values for several behavioral measures, including speed, freezing, erratic
      movement, and interindividual distance. In contrast, the manual coding of
      behavior in The Observer showed weaker correlations with the two tracking methods
      (EthoVision and Argus). Thus, Argus is a novel, cost-effective, and customizable
      method for the analysis of adult zebrafish behavior that may be utilized for the
      behavioral quantification of both single and dyadic interacting subjects, but
      further sophistication will be needed for the proper identification of complex
      motor patterns, measures that a human observers can easily detect.

PMID- 30105444
TI  - Analysis of single-case experimental count data using the linear mixed effects
      model: A simulation study.
AB  - When (meta-)analyzing single-case experimental design (SCED) studies by means of
      hierarchical or multilevel modeling, applied researchers almost exclusively rely
      on the linear mixed model (LMM). This type of model assumes that the residuals
      are normally distributed. However, very often SCED studies consider outcomes of a
      discrete rather than a continuous nature, like counts, percentages or rates. In
      those cases the normality assumption does not hold. The LMM can be extended into
      a generalized linear mixed model (GLMM), which can account for the discrete
      nature of SCED count data. In this simulation study, we look at the effects of
      misspecifying an LMM for SCED count data simulated according to a GLMM. We
      compare the performance of a misspecified LMM and of a GLMM in terms of goodness
      of fit, fixed effect parameter recovery, type I error rate, and power. Because
      the LMM and the GLMM do not estimate identical fixed effects, we provide a
      transformation to compare the fixed effect parameter recovery. The results show
      that, compared to the GLMM, the LMM has worse performance in terms of goodness of
      fit and power. Performance in terms of fixed effect parameter recovery is equally
      good for both models, and in terms of type I error rate the LMM performs better
      than the GLMM. Finally, we provide some guidelines for applied researchers about
      aspects to consider when using an LMM for analyzing SCED count data.

PMID- 30105445
TI  - Replication Bayes factors from evidence updating.
AB  - We describe a general method that allows experimenters to quantify the evidence
      from the data of a direct replication attempt given data already acquired from an
      original study. These so-called replication Bayes factors are a
      reconceptualization of the ones introduced by Verhagen and Wagenmakers (Journal
      of Experimental Psychology: General, 143(4), 1457-1475 2014) for the common t
      test. This reconceptualization is computationally simpler and generalizes easily
      to most common experimental designs for which Bayes factors are available.

PMID- 30105448
TI  - Heme oxygenase and iron status in exosomes of psoriasis patients.
AB  - Psoriasis is an autoimmune skin disease characterized by hyperproliferation of
      keratinocytes due to interplay between keratinocytes and immune cells. Iron
      status plays an important role in modifying the function of the immune system.
      Heme oxygenase (HO), heme-degrading enzyme, plays important role in protective
      response to oxidative cellular stress. We aimed in this study to map the iron
      status and HO levels and declare the role HO enzyme in iron homeostasis and
      immune-modulation in psoriasis. Fifty-one patients with psoriasis and 50 age- and
      sex-matched healthy controls were enrolled in this study. 5 mL blood sample was
      withdrawn from each subject. Hepcidin, iron soluble transferring receptor (sTfR),
      and total iron binding capacity (TIBC) were estimated using ELISA technique and,
      HO-1 gene level was detected using RT-PCR (reverse transcription-polymerase chain
      reaction). Iron levels, TIBC, and hepcidin were significantly lower in cases
      compared to controls. On the contrary, sTfR and HO-1 were significantly over
      expressed in cases compared to controls (p < 0.05 in all). HO-1 expression
      negatively correlated with PASI score and disease extent (%) (r = - 0.614-, p =
      0.001; r = - 0.807-, p = 0.001 respectively). There were no significant
      associations between HO-1 expression and iron, TIBC, hepcidin, sTfR levels (p >
      0.05 in all). Iron supplements for the patients with psoriasis are important to
      maintain haematopoiesis. The induction of HO-1 might have be a promising approach
      for the treatment of psoriasis through antioxidant ability, immunomodulatory role
      as well as its role in heme synthesis.

PMID- 30105446
TI  - Inhibition of glioma growth by a GOLPH3 siRNA-loaded cationic liposomes.
AB  - PURPOSE: GOLPH3 has been shown to be involved in glioma proliferation. In this
      study, we aimed to demonstrate that GOLPH3 can serve as a target for glioma gene
      therapy. METHODS: During the experiment, cationic liposomes with angiopep-2 (A2
      CL) were used to deliver siGOLPH3 crossing the blood-brain barrier and reaching
      the glioma. RESULTS: At the cellular level, the A2-CL/siGOLPH3 could silence
      GOLPH3 and then effectively inhibited the proliferation of cells. In vivo
      experiments, using U87-GFP-Luci-bearing BALB/c mouse models, we demonstrated that
      A2-CL could deliver GOLPH3-siRNA specifically to glioma and effectively inhibit
      glioma growth. CONCLUSIONS: This study shows that GOLPH3 has great potential as a
      target for the gene therapy of glioma and is of great value in precise medical
      applications.

PMID- 30105449
TI  - Caffeine delivery in porcine skin: a confocal Raman study.
AB  - Confocal Raman microscopy is a novel optical method for studies of pro-drug and
      drug delivery. This method is a promising technique that enables non-destructive
      measurement of the permeation profile through skin layers. Peaks of compounds are
      usually normalised to skin peaks (amino-acid and amide I) for semi-quantitative
      evaluation. The present study seeks to optimise a methodology for complete
      quantitative measurement of the amount of an active compound at different depths.
      Caffeine was used as a tracer to evaluate compound's skin penetration using
      confocal Raman microscopy. A semi-quantitative depth profile of caffeine was
      obtained with normalisation of the Raman intensities. These ratios of Raman
      intensities were correlated with the caffeine concentration using an external
      calibration curve. The calibration curve was carried out with porcine skin
      incubated in different concentrations of caffeine; afterwards, each skin sample
      was analysed by confocal Raman microscopy and HPLC to determine the relation
      between the Raman signal intensity and the caffeine concentration per skin mass
      and to create a depth profile. These correlation curves allow the full
      quantification of the caffeine in skin from Raman intensity ratios at different
      depths.

PMID- 30105450
TI  - Fluoroquinolone-resistant Achromobacter xylosoxidans clinical isolates from
      Serbia: high prevalence of the aac-(6')-Ib-cr gene among resistant isolates.
AB  - The aim of this study was to evaluate the contribution of plasmid-mediated genes
      and efflux to fluoroquinolone resistance in collection of Achromobacter spp.
      gathered during a 3-year period. Susceptibility to ciprofloxacin and levofloxacin
      was tested by disk diffusion and microdilution tests for a collection of 98
      Achromobacter spp. clinical isolates. Identification of fluoroquinolone-resistant
      isolates was performed by sequencing and phylogenetic analyses of the nrdA gene.
      Genetic relatedness among resistant isolates was determined by pulsed-field gel
      electrophoresis (PFGE) analysis. The influence of an H+ conductor cyanide m
      chlorophenyl hydrazone (CCCP) and a resistance-nodulation-division-type efflux
      pump inhibitor phenylalanine-arginine beta-naphthylamide (PAbetaN) on minimal
      inhibitory concentration (MIC) value was evaluated by broth microdilution. The
      presence of the plasmid-mediated qnrA, qnrB, qnrC, qnrS, and aac-(6')-Ib-cr genes
      was investigated by PCR and sequencing. Achromobacter spp. isolates that were
      resistant or intermediately resistant to fluoroquinolones in disk diffusion tests
      (44/98) were subjected to microdilution. As a result, 20/98 isolates were
      confirmed to be resistant to ciprofloxacin while 10/98 was resistant to
      levofloxacin. CCCP decreased twofold MIC value for ciprofloxacin in six isolates
      and more than 16 times in one isolate, while MIC value for levofloxacin was
      decreased in all isolates (twofold to more than eightfold). Fluoroquinolone
      resistant isolates were identified as A. xylosoxidans with the nrdA gene
      sequencing. PFGE revealed that resistant isolates belonged to seven different
      genotypes. Ten isolates belonging to four genotypes were positive for the aac
      (6')-Ib-cr gene. Although resistance to fluoroquinolones was not widespread among
      analyzed isolates, detected contribution of efflux pumps and the presence of the
      aac-(6')-Ib-cr gene present a platform for emergence of more resistant strains.

PMID- 30105447
TI  - Cell-specific gene therapy driven by an optimized hypoxia-regulated vector
      reduces choroidal neovascularization.
AB  - : Aberrant growth of blood vessels in the choroid layer of the eye, termed
      choroidal neovascularization (CNV), is the pathological hallmark of exudative age
      related macular degeneration (AMD), causing irreversible blindness among the
      elderly. Co-localization of proangiogenic factors and hypoxia inducible factors
      (HIF) in neovascular membranes from AMD eyes suggests the role of hypoxia in
      pathogenesis of CNV. In order to utilize hypoxic conditions in RPE for
      therapeutic purposes, we developed an optimized hypoxia regulated, RPE cell
      specific gene therapy to inhibit choroidal neovascularization. An adeno
      associated virus (AAV2) vector comprising a RPE-specific promoter and HIF-1
      response elements (HRE) was designed to regulate production of human endostatin
      (a powerful angiostatic protein) in RPE. The vector was tested in a mouse model
      of laser-induced CNV using subretinal delivery. Spectral domain optical coherence
      tomography (SD-OCT) images from live mice and confocal images from lectin stained
      RPE flat mount sections demonstrated reduction in CNV areas by 80% compared to
      untreated eyes. Quantitative real-time polymerase chain reaction (qPCR) confirmed
      exogenous endostatin mRNA expression from the regulated vector that was
      significantly elevated 3, 7, and 14 days following laser treatment, but its
      expression was completely shut off after 45 days. Thus, RPE-specific, hypoxia
      regulated delivery of anti-angiogenic proteins could be a valuable therapeutic
      approach to treat neovascular AMD at the time and in the ocular space where it
      arises. KEY POINTS: An optimized gene therapy vector targeting hypoxia and tissue
      specific expression has been designed. The inhibitory role of gene therapy vector
      was tested in a mouse model of laser-induced CNV. An 80% reduction in choroidal
      neovascularization was achieved by the optimized vector. The expression of
      endostatin was limited to retinal pigment epithelium and regulated by hypoxia.

PMID- 30105452
TI  - Assessment of the operational performances of two activated sludge systems in
      Kuwait.
AB  - Activated sludge systems (ASSs) are the most globally used wastewater treatment
      systems. However, there is very little information about the operational
      practices of ASSs in developing countries. This paper presents how the Riqqa and
      Umm-Al-Haiman ASSs, in Kuwait, are operated and the methodology used to evaluate
      and compare their performances. Over a period of 9 months, weekly samples of the
      influents, aeration tank mixed liquors, and secondary effluents were collected
      and analyzed according to standard methods. Accordingly, the operational
      variables of the systems were estimated. The obtained results indicate that the
      plants were not operated within their recommended design values. The Riqqa ASS
      was inadequately aerated and hydraulically and organically overloaded, while the
      Umm-Al-Haiman ASS was operated at a very high mixed liquor suspended solids
      (MLSS) value. The method used by this study proved to be useful for identifying
      the operational problems of the studied ASSs, and it can be used to evaluating
      the performances of other ASSs.

PMID- 30105451
TI  - Compensatory hypertrophy of the liver after external beam radiotherapy for
      primary liver cancer.
AB  - PURPOSE: We investigated whether external beam radiotherapy (EBRT) could induce
      compensatory liver hypertrophy in liver cancers and assessed related clinical
      factors. METHODS: A total of 82 consecutive patients receiving EBRT for
      hepatocellular carcinoma (n = 77) or cholangiocarcinoma (n = 5) from April 2012
      to June 2014 were recruited and divided into two subgroups according to tumor
      location in the right or left lobe. The left lateral and right lobes were
      considered as unirradiated volumes accordingly. Total liver volume (TLV),
      nontumor liver volume (NLV), left and right lobe whole volume (LLWV and RLWV,
      respectively), volume of liver irradiated < 30 Gy (V< 30 Gy), Child-Pugh (CPS)
      score, future liver remnant (FLR) ratio, and percentage of FLR hypertrophy from
      baseline (%FLR) were assessed. RESULTS: In the right lobe group, %FLR hypertrophy
      and LLWV increased significantly at all follow-ups (p < 0.001). %FLR hypertrophy
      steadily increased until the fourth follow-up. Multivariate analysis showed that
      the factor associated with maximum %FLR hypertrophy was tumor extent (upper or
      lower lobe vs. both lobes; p = 0.022). Post-RT treatments including transarterial
      chemoembolization or hepatic arterial infusion chemotherapy were associated with
      a CPS increase >= 2 (p = 0.002). Analysis of the RT only subgroup also showed a
      significant increase of %FLR until the fourth follow-up (p < 0.001). In the left
      lobe group, %FLR hypertrophy and RLWV showed no significant changes during follow
      up. CONCLUSION: Significant compensatory hypertrophy of the liver was observed,
      with a steady increase of %FLR hypertrophy until the fourth follow-up (median:
      396 days). Locally advanced tumors extending across the upper and lower right
      lobe were a significant factor for compensating hypertrophy after EBRT.

PMID- 30105453
TI  - Siponimod pharmacokinetics, safety, and tolerability in combination with
      rifampin, a CYP2C9/3A4 inducer, in healthy subjects.
AB  - PURPOSE: To assess the potential pharmacokinetic (PK) interactions between
      siponimod and rifampin, a strong CYP3A4/moderate CYP2C9 inducer, in healthy
      subjects. METHODS: This was a confirmatory, open-label, multiple-dose two-period
      study in healthy subjects (aged 18-45 years). In Period 1 (Days 1-12), siponimod
      was up-titrated from 0.25 to 2 mg over 5 days (Days 1-6) followed by 2 mg once
      daily on days 7-12. In Period 2, siponimod 2 mg qd was co-administered with
      rifampin 600 mg qd (Days 13-24). Primary assessments included PK of siponimod
      (Days 12 and 24; maximum steady-state plasma concentration [Cmax,ss], median time
      to achieve Cmax,ss [Tmax, ss], and area under the curve at steady state
      [AUCtau,ss]). Key secondary assessments were PK of M3 and M5 metabolites, and
      safety/tolerability including absolute lymphocyte count (ALC). RESULTS: Of the 16
      subjects enrolled (age, mean +/- standard deviation [SD] 31 +/- 8.3 years; men, n
      = 15), 15 completed the study. In Period 1, siponimod geometric mean Cmax,ss
      (28.6 ng/mL) was achieved in 4 h (median Tmax,ss; range, 1.58-8.00) and the
      geometric mean AUCtau,ss was 546 h * ng/mL. In Period 2, the siponimod geometric
      mean Cmax,ss and AUCtau,ss decreased to 15.7 ng/mL and 235 h * ng/mL,
      respectively; median Tmax remained unchanged (4 h). Rifampin co-administration
      increased M3 Cmax,ss by 53% while M5 Cmax,ss remained unchanged. The AUCtau,ss of
      M3 and M5 decreased by 10% and 37%, respectively. The majority of adverse events
      reported were mild, with a higher frequency during Period 2 (86.7%) versus Period
      1 (50%). The mean ALC increased slightly under rifampin co-administration but
      remained below 1.0 * 109/L. CONCLUSIONS: The study findings suggest that in the
      presence of rifampin, a strong CYP3A4/moderate CYP2C9 inducer, siponimod showed
      significant decrease in Cmax,ss (45%) and AUCtau,ss (57%) in healthy subjects.

PMID- 30105454
TI  - Epidemiology, prevention, screening, diagnosis, and evaluation: update of the
      ICUD-SIU joint consultation on bladder cancer.
AB  - PURPOSE: To update current recommendations on prevention, screening, diagnosis,
      and evaluation of bladder cancer (BC) based on a thorough assessment of the most
      recent literature on these topics. METHODS: A non-systematic review was
      performed, including articles until June 2017. A variety of original articles,
      reviews, and editorials were selected according to their epidemiologic,
      demographic, and clinical relevance. Assessment of the level of evidence and
      grade of recommendations was performed according to the International
      Consultation on Urological Diseases grading system. RESULTS: BC is the ninth most
      common cancer worldwide with 430,000 new cases in 2012. Currently, approximately
      165,000 people die from the disease annually. Absolute incidence and prevalence
      of BC are expected to rise significantly during the next decades because of
      population ageing. Tobacco smoking is still the main risk factor, accounting for
      about 50% of cases. Smoking cessation is, therefore, the most relevant
      recommendation in terms of prevention, as the risk of developing BC drops almost
      40% within 5 years of cessation. BC screening is not recommended for the general
      population. BC diagnosis remains mainly based on cystoscopy, but development of
      new endoscopic and imaging technologies may rapidly change the diagnosis
      algorithm. The same applies for local, regional, and distant staging modalities.
      CONCLUSIONS: A thorough understanding of epidemiology, risk factors, early
      detection strategies, diagnosis, and evaluation is essential for correct,
      evidence-based management of BC patients. Recent developments in endoscopic
      techniques and imaging raise the hope for providing better risk-adopted
      approaches and thereby improving clinical outcomes.

PMID- 30105456
TI  - Shock wave lithotripsy versus endoscopic cystolitholapaxy in the management of
      patients presenting with calcular acute urinary retention: a randomised
      controlled trial.
AB  - PURPOSE: Shock wave lithotripsy (SWL) in treatment of bladder and urethral stones
      was not precisely determined. The objective of this study is to compare the
      efficacy and safety of SWL versus visual cystolitholapaxy in the management of
      calcular acute urine retention. METHODS: From March 2015 to February 2017, a
      randomised controlled study was conducted on 100 patients for whom urethral
      catheter fixed for acute retention of urine due to urethral or vesical radio
      opaque stone(s) <= 2 cm. Patients were randomised to either SWL group (n = 50) or
      visual cystolitholapaxy (endoscopy group) (n = 50). RESULTS: No statistically
      significant differences between the pre-operative parameters of both groups were
      found. The mean stone diameter was 12.2 +/- 3 mm and 12.2 +/- 3.2 mm in SWL and
      endoscopy groups, respectively (p value = 0.4). The overall success rates of SWL
      group were 94% (47 of 50 patients) and endoscopy group were 98% (49 of 50
      patients). SWL failed in 3 patients (6%); these 3 patients underwent
      cystolitholapaxy and were rendered free of stones. Intra-operative and post
      operative complications were comparable between both groups (p value = 0.5 and 1,
      respectively). One patient had bladder perforation in the endoscopy group and was
      managed conservatively. CONCLUSIONS: SWL mono-therapy is safe, non-invasive and
      as effective as visual cystolitholapaxy in management of patients presenting with
      acute urine retention by vesical or urethral stones 2 cm or less and could be
      useful for patients unwilling/unfit for general anaesthesia.

PMID- 30105455
TI  - The urological management of children with spinal cord injury.
AB  - BACKGROUND: The urologic management of children with spinal cord injury (SCI)
      differs from that of the adult insofar as the care involves a developing organ
      system and will be ongoing for years. Preservation of renal function as well as
      prevention of urinary tract infection in concert with both bladder and bowel
      continence are the essential guiding principles. METHODS: This is a non
      systematic review of the literature and represents expert opinion where data are
      non-existent. This review focuses on special considerations in children with
      spinal cord injuries. RESULTS: SCI in children is less frequent than in adults
      and affects mainly older children and teenagers. The etiology of SCI in children
      is usually motor vehicle accidents. The cervical spine is often injured. The
      urologic evaluation is similar to that for adults but may involve more frequent
      radiologic and urodynamic assessment to monitor renal function as the child
      grows. CONCLUSIONS: Treatment may be divided into medical vs. surgical and
      mirrors the approach to children who have a neurogenic bladder due to spina
      bifida. Bladder management should be associated with bowel management to achieve
      the goals of continence and social acceptability.

PMID- 30105458
TI  - A new non-dilution rapid desensitization protocol successfully applied to all
      grade platinum hypersensitivity.
AB  - PURPOSE: Desensitization is a safe alternative for patients with hypersensitivity
      reactions (HSRs) to platinum-based chemotherapeutic agents and widely used in
      real practice by employing stepwise administration of multiple serial dilutions
      of the culprit drugs. However, its labor-intensive nature has required a simpler
      protocol that is easier to prepare and perform. METHODS: We performed an
      observational study of patients with platinum HSR who underwent a new non
      dilution one-bag desensitization protocol. Premedication consisted of Montelukast
      as well as H1 and H2 blockers. The outcomes and safety profiles of a new protocol
      were assessed. RESULTS: A total of 36 patients were recruited (oxaliplatin 23,
      carboplatin 9, and cisplatin 4) and the most common grade of HSR presented was
      grade 2 (61.1%), followed by grade 3 (25%), and grade 1 (13.9%). Of 175
      desensitization procedures, all cases were successfully completed in re
      administration of culprit chemotherapeutic platinum agents; 146 (83.4%) had no
      breakthrough reactions (BTRs) while 29 (16.6%) did. Most BTRs were mild reactions
      (grade 1, 51.7%) or moderate reactions (grade 2, 44.8%) of Brown's Scale.
      Although there was one case of asymptomatic mild hypotension (grade 3, 3.5%),
      categorized as severe reaction, dyspnea, desaturation, and anaphylaxis did not
      occur. The proportion of severe HSRs was significantly lower than that of initial
      HSRs (3.5% vs. 25%, P = 0.0167). CONCLUSIONS: The new non-dilution
      desensitization protocol was safe and effective for re-administration of culprit
      platinum agents in patients with a history of HSRs. Therefore, this new protocol
      can be used as an alternative to existing protocols using multiple serial
      dilutions.

PMID- 30105459
TI  - Comparative study of the effects of venlafaxine and duloxetine on chemotherapy
      induced peripheral neuropathy.
AB  - OBJECTIVE: One of the complications of chemotherapy is peripheral neuropathy.
      Various studies have shown that potent norepinephrine and serotonin reuptake
      inhibitors such as gabapentin, venlafaxine and duloxetine have therapeutic
      effects on neuropathy. The aim of this study was to compare the effects of
      venlafaxine vs. duloxetine on chemotherapy-induced peripheral neuropathy.
      METHODS: In this clinical trial, cancer patients who were suffering from
      chemotherapy-induced peripheral neuropathy comprised the study population. They
      were randomly assigned to three pharmacotherapy groups including venlafaxine,
      duloxetine and placebo. Cranial, sensory, motor neuropathies as well as
      neuropathic pain were evaluated on day 1, week 2, and week 4 after enrollment.
      RESULTS: Grade of cranial, motor, sensory and neuropathic pain decreased
      significantly in venlafaxine and duloxetine groups. This reduction was more
      considerable in duloxetine group compared to venlafaxine group (P < 0.05).
      CONCLUSION: Duloxetine seems to be more effective than venlafaxine in decreasing
      the symptoms of chemotherapy-induced peripheral neuropathy. Duloxetine was more
      effective than venlafaxine in decreasing motor neuropathy and neuropathic pain
      grade.

PMID- 30105460
TI  - Lapatinib with ECF/X in the first-line treatment of metastatic gastric cancer
      according to HER2neu and EGFR status: a randomized placebo-controlled phase II
      study (EORTC 40071).
AB  - PURPOSE: HER2-targeted therapy with trastuzumab and (CF/X) prolonged overall
      survival (OS) in metastatic HER2neu+ gastric carcinoma (GC). Lapatinib inhibits
      both EGFR and HER2neu. We investigated the efficacy and safety of lapatinib with
      epirubicin (E) + CF/X in GC according to HER2neu and EGFR status. METHODS: Tumors
      from chemotherapy-naive patients were screened centrally by fluorescence in situ
      hybridization (FISH) and immunohistochemistry (IHC). Patients with EGFR and/or
      HER2neu expression or amplification were allocated to three strata based on
      EGFR/HER2neu status and were randomized to lapatinib (arm A) or placebo (arm B),
      with 6 cycles of ECF or ECX (investigator-selected). The primary endpoint was
      progression-free survival (PFS) in stratum 3. RESULTS: 29 of 72 screened patients
      were randomized to strata 1 (HER2neu+: by FISH and IHC, n = 6), 2 (HER2neu-: by
      FISH/+ by IHC, n = 5) and 3 (HER2neu-/EGFR+, n = 18), of which 28 patients were
      eligible (14 per arm). Enrollment was curtailed after announcement of the
      negative LOGiC trial results. Median PFS was 8.0 versus 5.9 months (HR = 0.86,
      95% CI 0.37-1.99) in the per protocol population, and 8.0 versus 6.3 months (HR =
      0.85, 95% CI 0.30-2.46) for stratum 3, in the lapatinib versus placebo arm
      respectively. Median OS was 13.8 versus 10.1 months, respectively (HR = 0.90, 95%
      CI 0.35-2.27). There were no safety concerns. CONCLUSIONS: Central EGFR and
      HER2neu stratification by IHC and FISH can be used for further pan-HER
      strategies. Lapatinib with ECF/X was well tolerated, but did not show clear
      activity in patients with metastatic GC.

PMID- 30105461
TI  - In vitro UGT1A1 inhibition by tyrosine kinase inhibitors and association with
      drug-induced hyperbilirubinemia.
AB  - PURPOSE: Hyperbilirubinemia has been observed in patients treated with tyrosine
      kinase inhibitor (TKI) drugs. Therefore, it would be beneficial to understand
      whether there is a relationship between inhibition of uridine-5'-diphosphate
      glucuronosyltransferase (UGT) 1A1 activity and observed bilirubin elevations in
      TKI drug-treated patients. UGT1A1 is responsible for the glucuronidation of
      bilirubin which leads to its elimination in the bile. METHODS: To examine this
      question, an in vitro glucuronidation assay was developed to determine the
      inhibitory effect of TKI drugs employing human liver microsomes (HLM) with
      varying UGT1A1 activity. Utilizing beta-estradiol as the UGT1A1 probe substrate,
      20 TKI drugs were evaluated at concentrations that represent clinical plasma
      levels. Adverse event reports were searched to generate an empirical Bayes
      geometric mean (EGBM) score for clinical hyperbilirubinemia with the TKI drugs.
      RESULTS: Erlotinib, nilotinib, regorafenib, pazopanib, sorafenib and vemurafenib
      had IC50 values that were lower than their clinical steady-state Cmax
      concentrations. These TKI drugs had high incidences of hyperbilirubinemia and
      higher EBGM scores. The IC50 values and Cmax/IC50 ratios correlated well with
      EBGM scores for hyperbilirubinemia (P < 0.005). For the TKI drugs with higher
      incidence of hyperbilirubinemia in Gilbert syndrome patients, who have reduced
      UGT1A1 activity, six of eight had smaller ratios in the low UGT1A1 activity
      microsomes than the wild-type microsomes for drugs, indicating greater
      sensitivity to the drugs in this phenotype. CONCLUSIONS: These results suggest
      that in vitro UGT1A1 inhibition assays have the potential to predict clinical
      hyperbilirubinemia.

PMID- 30105462
TI  - Substantial evidence for the clinical significance of missense variant BRCA1
      c.5309G>T p.(Gly1770Val).
AB  - PURPOSE: Classification of rare BRCA1 missense variants presents a major
      challenge for the counseling and treatment of patients. Variant classification
      can be complicated by conflicting lines of evidence. BRCA1 c.5309G>T
      p.(Gly1770Val) has been shown to abrogate BRCA1 protein homologous DNA repair;
      however, multiple sequence alignment demonstrates a lack of sequence conservation
      at this position, suggesting that glycine at position 1770 may not be essential
      for cellular maintenance in humans. We analyzed clinical information to resolve
      the classification of BRCA1 c.5309G>T p.(Gly1770Val). METHODS: We performed
      multifactorial likelihood analysis combining segregation data for 14 informative
      families, and breast tumor histopathological data for 17 variant carriers,
      ascertained through the ENIGMA consortium. RESULTS: Bayes segregation analysis
      gave a likelihood ratio of 101:1 in favor of pathogenicity. The vast majority of
      breast tumors showed features indicative of pathogenic variant carrier status,
      resulting in a likelihood ratio of 15800794:1 towards pathogenicity. Despite a
      low prior probability of pathogenicity (0.03) based on bioinformatic prediction,
      multifactorial likelihood analysis including segregation and histopathology
      analysis gave a posterior probability of > 0.99 and final classification of
      Pathogenic. CONCLUSIONS: We provide evidence that BRCA1 c.5309G>T p.(Gly1770Val),
      previously described as a Moroccan founder variant, should be treated as a
      disease-causing variant despite a lack of evolutionary conservation at this amino
      acid position. Additionally, we stress that bioinformatic information should be
      used in combination with other data, either direct clinical evidence or some form
      of clinical calibration, to arrive at a final clinical classification.

PMID- 30105457
TI  - The nucleolus, an ally, and an enemy of cancer cells.
AB  - The rates of ribosome production by a nucleolus and of protein biosynthesis by
      ribosomes are tightly correlated with the rate of cell growth and proliferation.
      All these processes must be matched and appropriately regulated to provide
      optimal cell functioning. Deregulation of certain factors, including oncogenes,
      controlling these processes, especially ribosome biosynthesis, can lead to cell
      transformation. Cancer cells are characterized by intense ribosome biosynthesis
      which is advantageous for their growth and proliferation. On the other hand, this
      feature can be engaged as an anticancer strategy. Numerous nucleolar factors such
      as nucleolar and ribosomal proteins as well as different RNAs, in addition to
      their role in ribosome biosynthesis, have other functions, including those
      associated with cancer biology. Some of them can contribute to cell
      transformation and cancer development. Others, under stress evoked by different
      factors which often hamper function of nucleoli and thus induce
      nucleolar/ribosomal stress, can participate in combating cancer cells. In this
      sense, intentional application of therapeutic agents affecting ribosome
      biosynthesis can cause either release of these molecules from nucleoli or their
      de novo biosynthesis to mediate the activation of pathways leading to elimination
      of harmful cells. This review underlines the role of a nucleolus not only as a
      ribosome constituting apparatus but also as a hub of both positive and negative
      control of cancer development. The article is mainly based on original papers
      concerning mechanisms in which the nucleolus is implicated directly or indirectly
      in processes associated with neoplasia.

PMID- 30105464
TI  - Impact of Pulmonary Valve Regurgitation on Pressure Difference of Pulmonary Valve
      Stenosis in Patients with Tetralogy of Fallot After Repair.
AB  - Pressure difference (PD) is an important parameter in evaluating the degree of
      stenotic lesion. However, PD is influenced by the blood flow volume passing
      through the stenosis. In patients with tetralogy of Fallot (TOF), pulmonary valve
      regurgitation (PR) and pulmonary valve stenosis (vPS) are common post-operative
      complications. The aim of this study was to evaluate the influence of PR on the
      PD. First, we examined the relationship between the peak-to-peak PD and the valve
      orifice area in 7 patients with vPS from their cardiac catheterization data.
      Second, an estimated PD, i.e., PD assuming no PR, was calculated in 8 patients
      with TOF with vPS and PR from their valve orifice area using the relational
      equation in patients with vPS. Moreover, an excess of PD, equating to the
      difference between the measured and estimated PD, was calculated. Finally, the
      relationship between the regurgitant fraction (RF) and the excess PD was
      analyzed. There was a strong relationship between the reciprocal of the valve
      orifice area and the PD in patients with vPS (r = 0.904, p = 0.0053). The excess
      PD showed a significant correlation with the RF in patients with TOF (r = 0.889,
      p = 0.0032). PR of over 25% in RF augmented the PD depending on the regurgitant
      volume. Severity of vPS could be overestimated in post-operative patients with
      TOF who had significant PR when their RF was above 25%.

PMID- 30105463
TI  - Hybrid Pulmonary Vein Stenting in Infants with Refractory to Surgical Pulmonary
      Vein Stenosis Repair.
AB  - Pulmonary vein stenosis (PVS) is still a frustrating disease with extremely high
      mortality, especially in children with multiple severe PVS. Hybrid pulmonary vein
      stenting (HPVS) is a rescue treatment for recurrent and malignant PVS. The aim of
      this study is to share our successful experience with intraoperative HPVS for
      recurrent PVS after total anomalous pulmonary venous connection (TAPVC) repair in
      infant. Six patients were identified between 2013 and January 2018, who were
      diagnosed with recurrent PVS and underwent HPVS in the operating room. The mean
      age at the time of the HPVS was 10.3 +/- 2.7 months (range 7-14 months) and the
      mean body weight was 7.9 +/- 2.6 kg (range 4.1-10.5 kg). Prior pulmonary vein
      surgery had been performed on average 2.7 times (range 2-3) in all patients. We
      used a bare-metal stent (BMS) of 6-8 mm diameter in 15 veins of five patients and
      a drug-eluting coronary stent (DES) in two veins of one patient. All patients had
      undergone several elective further pulmonary vein in-stent balloon dilatations or
      another stent insertion after HPVS. Over a mean follow-up of 17.3 +/- 13.7 months
      (range 6-44 months), all patients maintained patency of stents although two
      patients died due to respiratory failure not associated with PVS. HPVS is a
      useful treatment modality for recurrent PVS patient that could save the life and
      achieve longer freedom from restenosis than repetitive surgical pulmonary vein
      widening only. Even though the prognosis of severe multiple PVS is very poor,
      planned HPVS could be a good palliation in this patients group.

PMID- 30105465
TI  - Complex Decision Making in the Pediatric Catheterization Laboratory:
      Catheterizer, Know Thyself and the Data.
AB  - Optimal outcomes are as much influenced by critical decision making pathways as
      by the technical skill of the operator. The complexity and potential cognitive
      traps underlying critical decision making has long been recognized in the
      aviation and business communities, however, remains a largely subconscious,
      unexamined discipline amongst congenital cardiac interventionalists. Challenges
      to making good decisions in the catheterization laboratory include heuristics,
      biases, and cognitive traps. In this paper we discuss some of the more common
      decision making challenges encountered and we address potential solutions to such
      decision making with particular focus towards standardization.

PMID- 30105466
TI  - Use of Speckle Tracking Echocardiography to Assess Left Ventricular Systolic
      Function in Patients with Surgically Repaired Tetralogy of Fallot: Global and
      Segmental Assessment.
AB  - Patients with repaired Tetralogy of Fallot (rToF) can have significant right and
      left ventricular dysfunction which can impact clinical outcome. Conventional
      echocardiographic evaluation using ejection fraction can be limited in detecting
      early stages of deteriorating left ventricular (LV) systolic function. Speckle
      tracking echocardiography (STE) provides a promising emerging tool for early
      detection of LV systolic dysfunction. The aim of this cross-sectional study is to
      evaluate the left ventricular global and regional function using STE in rToF
      patients with preserved left ventricular ejection fraction to detect early signs
      of LV dysfunction. The study is a retrospective review of the medical records and
      transthoracic echocardiograms of rTOF patients who were seen in the pediatric
      cardiology clinic at our institution from August 2016 till May 2018. The rTOF
      group was compared with a matched healthy control group. Offline strain analysis
      of TTE studies was completed in each subject according to mode set by the
      American Society of Echocardiography. Twenty-two patients with rTOF and 22 age
      matched controls (rTOF 18.7 +/- 6 years and control 14.6 +/- 9.6 years, P value
      0.19) were included during the study period. The rTOF group consisted of 12 males
      and 10 females, whereas the control group consisted of 15 males and 7 females.
      There was no significant difference in terms of LV ejection fraction using both 2
      chamber as well as 4-chamber views. Global LV longitudinal strain was
      significantly lower in the rTOF group compared with the control group (rTOF -
      15.92 +/- 3.16 vs control - 22.79 +/- 2.45, P value 0.00). All 17 segments showed
      significantly lower longitudinal strains in rTOF group compared with the control
      group. Global circumferential left ventricle strain was significantly lower in
      the rTOF patients compared with the control group (- 17.24 +/- 5.86 vs - 22.74 +/
      3.99, P value 0.001). 13 out of 16 segments had lower circumferential strains in
      the rTOF patients compared with controls. Asymptomatic surgically repaired TOF
      patients exhibited abnormal segmental and global left ventricle longitudinal and
      circumferential strains despite having normal left ventricle ejection fraction.
      Our findings suggest subclinical damage to the left ventricle systolic function
      post-surgical repair of TOF. 2-D speckle-tracking echocardiography may be used as
      a valuable method in the early recognition of left myocardial systolic function
      impairment in patients after TOF repair. The application of this method to guide
      clinical decision and management of rTOF patients such as earlier pulmonary valve
      replacement or risk stratification for sudden cardiac death needs further
      investigation.

PMID- 30105468
TI  - Targeted Next-Generation Sequencing of 406 Genes Identified Genetic Defects
      Underlying Congenital Heart Disease in Down Syndrome Patients.
AB  - Down syndrome (DS) is the most common autosomal chromosome anomaly. DS is
      frequently associated with congenital heart disease (CHD). Patients with DS have
      40-60% chance of having CHD. It means that CHD in DS is not only due to trisomy
      21 and there are some other genetic factors underlying CHD in DS children. In
      this study, a total of 240 DNA samples from patients were analyzed including 100
      patients with CHD only, 110 patients having CHD along with DS and 30 patients
      with isolated DS. A cardiovascular gene panel consisting of probes for 406 genes
      was used to screen DNA samples of all 240 patients for mutation identification.
      All variants were annotated and common variants were obtained. Briefly, 28 common
      variants (variants common in two or more than two individuals) were obtained in a
      group of samples containing DNA from DS patients having CHD as well, 63 variants
      were found to be unique to DS group of samples and 73 variants have been
      identified in patients with CHD only. In order to identify genomic variations
      determining the risk for CHD in DS, only those variants present in DS-CHD group
      and absent in isolated CHD and/or isolated DS group were considered for further
      analysis. Variants specific to DS-CHD group were further evaluated based on
      expression and function data and pathogenicity of the variant of interest. We
      have implicated mutations in GATA3, KCNH2, ENG, FLNA, and GUSB genes as an
      underlying risk factor for CHD in DS patients.

PMID- 30105467
TI  - Determination of the Frequency of Right and Left Internal Mammary Artery
      Embolization in Single Ventricle Patients: A Two-Center Study.
AB  - Embolization of systemic to pulmonary artery collaterals to regulate pulmonary
      arterial flow or pressure of the cavopulmonary circulation in patients with
      single ventricle is a common practice. The relative incidence and impact of this
      practice on future interventions like coronary artery bypass grafting is poorly
      understood. This study aims to evaluate the frequency and implications of
      internal mammary artery (IMA) embolization in the single ventricle (SV)
      population. A retrospective chart review was performed of SV patients who
      underwent cardiac catheterization before and after Fontan procedure between
      February 2007 and 2017. Data were collected from two tertiary care centers in the
      Midwest. Of the 304 SV patients, 62 (20.4%) underwent embolization of one or more
      IMAs, whereas 242 (79.6%) did not. The rate of embolization of IMA was 40.5% in
      one center and 14.5% in the second center. Among patients who received IMA
      embolization, left internal mammary artery (LIMA) embolization was seen in 6
      (9.7%) patients. Majority of patients underwent either right internal mammary
      artery (RIMA) embolization (n = 25; 40.3%) or RIMA and LIMA embolization (n = 27;
      43.5%). IMA embolization in SV patients is common. Embolizing IMAs early in life
      will likely eliminate a valuable graft option for coronary artery bypass grafting
      should it be required in the future care of these patients. Multi-center,
      prospective, nation-wide studies are warranted to examine coronary artery disease
      in the SV population and true frequency of IMA embolization. Delineation of which
      IMAs were embolized is a necessary in surgical and cardiac intervention national
      data, such as Society of Thoracic Surgeons (STS) database. All measures should be
      taken to preserve IMAs patency, if deemed feasible and safe.

PMID- 30105470
TI  - Glucokinase deficit and birthweight: does maternal hyperglycemia always meet
      fetal needs?
AB  - AIMS: Many authors do not recommend hypoglycemic treatment during pregnancy in
      women affected by monogenic diabetes due to heterozygous glucokinase (GCK)
      mutations (MODY 2) in case of affected fetus, because maternal hyperglycemia
      would be necessary to achieve a normal birthweight. We aimed to evaluate
      differences in birthweight between MODY 2 affected children according to the
      parent who carried the mutation. METHODS: We retrospectively studied 48 MODY 2
      affected children, whose mothers did not receive hypoglycemic treatment during
      pregnancy, divided into two groups according to the presence of the mutation in
      the mother (group A) or in the father (group B). Data were extracted from the
      database of the Regional Centre of Pediatric Diabetology of the University of
      Campania, Naples, collected from 1996 to 2016. We analyzed birthweight and
      centile birthweight. RESULTS: Percentage of small for gestational age was
      significantly higher in group B than in group A. We found three large for
      gestational age in the group that inherited the deficit from the mother, all with
      the same novel GCK mutation (p.Lys458-Cys461del). CONCLUSIONS: We hypothesize
      that not all MODY 2 affected fetuses need the same levels of hyperglycemia to
      have an appropriate growth, maybe because different kinds of GCK mutations may
      result in different phenotypes. Consequently, a "tailored therapy" of maternal
      hyperglycemia, based on fetal growth frequently monitored through ultrasounds, is
      essential in MODY 2 pregnancies.

PMID- 30105469
TI  - Urinary tubular biomarkers as predictors of kidney function decline,
      cardiovascular events and mortality in microalbuminuric type 2 diabetic patients.
AB  - AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil
      gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology
      and have been proposed as risk markers for development of complications in
      patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1
      and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause
      mortality in patients with T2D and persistent microalbuminuria without clinical
      cardiovascular disease. METHODS: This is a prospective study that included 200
      patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192
      patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and
      nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction,
      stroke, ischemic heart disease and heart failure based on national hospital
      discharge registries, and all-cause mortality. Adjusted Cox models included
      traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1
      standard deviation (SD) increment of log2-transformed values. Relative integrated
      discrimination improvement (rIDI) was calculated. RESULTS: During the 6.1 years'
      follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34)
      and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04
      2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u
      KIM-1 contributed significantly to risk prediction for all-cause mortality
      evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the
      outcomes after adjustment. CONCLUSIONS: In patients with T2D and persistent
      microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for
      decline in eGFR, CVE and all-cause mortality, and contributed significant
      discrimination for all-cause mortality, beyond traditional risk factors.

PMID- 30105471
TI  - Fatal Poisonings Associated with New Psychoactive Substances.
AB  - This chapter describes how new psychoactive substances (NPS) have been involved
      in fatal intoxications from 2010 and onwards. It summarizes the circumstances,
      antemortem symptoms, and adverse effects that have led to death after ingestion
      of one or more NPS and tabulates concentrations, and postmortem findings from
      these intoxications.Consumption of NPS exerts health problems and unknown risks
      for the users. Data on toxicity of many NPS are scarce or nonexistent and long
      term toxicity and risks are still largely unknown. In addition, purity and
      composition of products containing NPS are often inconsistent or not known, which
      places users at high risk as evidenced by hospital emergency admissions and
      deaths.The most serious threat to drug users are the synthetic opioids that with
      strong central nervous depressant effects have caused numerous accidental deaths
      spread over the entire globe. The synthetic cannabinoids seem to be the most
      unpredictable with no clear toxidrome and unknown or poorly understood mechanisms
      of toxicity, but with adverse effects pointing toward the cardiovascular system.
      The toxidromes commonly encountered after ingestion of cathinones and
      phenethylamines are of sympathomimetic and hallucinogenic character, which
      includes risk of developing a serotonin syndrome, excited delirium, and life
      threatening cardiovascular effects. In comparison to their conventional "parent"
      drug, i.e., heroin, cannabis, and amphetamine, most NPS appear to exhibit more
      severe adverse effects. The deaths attributed to NPS have dramatically increased
      in the last years. In our opinion, this is because of the shift from synthetic
      cannabinoids and cathinones to the even more toxic and dangerously potent
      fentanyl analogues.

PMID- 30105472
TI  - Tricyclic Antidepressants and Monoamine Oxidase Inhibitors: Are They Too Old for
      a New Look?
AB  - Through unintentional discovery, monoamine oxidase inhibitors (MAOIs) and
      tricyclic antidepressants (TCAs) were the first antidepressant classes to be used
      clinically and have been widely available for over half a century. From the 1950s
      to the 1980s, these two classes of antidepressants were the sole antidepressant
      tools available to psychiatrists. With the advent of the selective serotonin
      reuptake inhibitors (SSRIs) in the 1980s and 1990s, the prescribing of the MAOIs
      and TCAs has fallen significantly worldwide. In this chapter, we take a closer
      look at the arc of MAOI discovery and clinical use, and how these two classes of
      drugs compare to each other. This is important because relatively few studies
      compare these older classes of drugs to the newer classes of antidepressants.
      Finally, we argue that TCAs, and particularly MAOIs, should continue to play an
      important role in the modern treatment of depression, especially in the treatment
      resistant patient.

PMID- 30105473
TI  - The Chemistry and Pharmacology of Synthetic Cannabinoid Receptor Agonist New
      Psychoactive Substances: Evolution.
AB  - Synthetic cannabinoid receptor agonists (SCRAs) are the largest and most
      structurally diverse class of new psychoactive substances (NPS). Although the
      earliest SCRA NPS were simply repurposed from historical academic manuscripts or
      pharmaceutical patents describing cannabinoid ligands, recent examples bear
      hallmarks of rational design. SCRA NPS manufacturers have applied traditional
      medicinal chemistry strategies (such as molecular hybridization, bioisosteric
      replacement, and scaffold hopping) to existing cannabinoid templates in order to
      generate new molecules that circumvent structure-based legislation. Most SCRAs
      potently activate cannabinoid type 1 and type 2 receptors (CB1 and CB2,
      respectively), with the former contributing to the psychoactivity of these
      substances. SCRAs are generally more toxic than the Delta9-tetrahydrocannabinol
      (Delta9-THC) found in cannabis, and this may be due to ligand bias, metabolism,
      or off-target activity. This chapter will chart the evolution of recently
      identified SCRA NPS chemotypes, as well as their putative manufacturing by
      products and thermolytic degradants, and describe structure-activity
      relationships within each class.

PMID- 30105474
TI  - Phencyclidine-Based New Psychoactive Substances.
AB  - The serendipitous discovery of phencyclidine (PCP) in 1956 sets the stage for
      significant research efforts that resulted in a plethora of analogs and
      derivatives designed to explore the biological effects of this class. PCP soon
      became the prototypical dissociative agent that eventually sneaked through the
      doors of clinical laboratories and became an established street drug. Estimations
      suggest that around 14 PCP analogs were identified as "street drugs" in the
      period between the 1960s and 1990s. Fast forward to the 2000s, and largely
      facilitated by advancements in electronic forms of communication made possible
      through the Internet, a variety of new PCP analogs began to attract the attention
      of communities interested in the collaborative exploration of these substances.
      Traditionally, as was the case with the first-generation analogs identified in
      previous decades, the substances explored represented compounds already known in
      the scientific literature. As the decade of the noughties unfolded, a number of
      new PCP-derived substances appeared on the scene, which included some analogs
      that have not been previously recorded in the published literature. The aim of
      this chapter is to present a brief introductory overview of substances that have
      materialized as PCP-derived new psychoactive substances (NPS) in recent years and
      their known pharmacology. Since N-methyl-D-aspartate receptor (NMDAR) antagonism
      is implicated in mediating the subjective and mind-altering effects of many
      dissociative drugs, additional data are included from other analogs not presently
      identified as NPS.

PMID- 30105475
TI  - Macrolide sesquiterpene pyridine alkaloids from the stems of Tripterygium
      regelii.
AB  - Nine new monomacrolide sesquiterpene pyridine alkaloids, macroregelines A-I (1
      9), were isolated from the stems of Tripterygium regelii, along with a known
      alkaloid, tripfordine B. The structures of all the isolated compounds were
      characterized by extensive one-dimensional (1D) and two-dimensional (2D) nuclear
      magnetic resonance (NMR) spectroscopic analyses, as well as high-resolution
      electrospray-ionization mass spectrometry (HRESIMS) data. Compounds 4, 5, 6, and
      8 showed antiproliferative effect on human rheumatoid arthritis synovial cell
      line MH7A at concentration of 20 MUM, reducing their viability by 7.5, 18.0, 9.0,
      and 18.2 %, respectively.

PMID- 30105477
TI  - Hemodynamic vise in obstructed total anomalous pulmonary venous connection.

PMID- 30105476
TI  - Biochemical characterization and spatio-temporal analysis of the putative L-DOPA
      pathway in Mucuna pruriens.
AB  - MAIN CONCLUSION: Transcriptome analysis and biochemical characterization of the
      putative l-3,4-dihydroxyphenylalanine (l-DOPA) pathway in Mucuna pruriens (L.) DC
      have been performed. Spatio-temporal quantification of the putative l-DOPA
      biosynthetic pathway genes and its correlation with respective metabolites was
      established. l-tyrosine, l-DOPA, and dopamine from all plant parts were
      quantified. The de novo transcriptome analysis was performed using leaves of the
      selected M. pruriens mutant T-IV-9 during maturity. The putative L-DOPA pathway
      and its regulatory genes were retrieved from transcriptome data and the L-DOPA
      pathway was biochemically characterized. The spatial and temporal gene expression
      for the L-DOPA pathway was identified with respect to the chemical constituents.
      L-tyrosine, L-DOPA, and dopamine contents were highest in leaves during maturity
      (about 170-day-old plants). The polyphenol oxidase (PPO) was highly expressed in
      tender stems (230-fold higher as compared to seeds) as well as a high L-DOPA
      content. The PPO gene was highly expressed in leaves (3367.93 in FPKM) with a 79
      fold increase compared to control plants during maturity. L-DOPA was found in
      every part with varied levels. The highest L-DOPA content was found in mature
      dried seed (3.18-5.8%), whereas the lowest amount was recorded in mature and
      dried leaves. The reproductive parts of the plant had a higher amount of L-DOPA
      content (0.9-5.8%) compared to the vegetative parts (0.2-0.91%). Various amino
      acid transporters and permeases were expressed in M. pruriens. The transcripts of
      dopa decarboxylase (DDC) were found in almost all parts of the plant, but its
      higher content was limited to the leaf.

PMID- 30105478
TI  - Impact of P-Glycoprotein on Intestinal Absorption of an Inhibitor of Apoptosis
      Protein Antagonist in Rats: Mechanisms of Nonlinear Pharmacokinetics and Food
      Effects.
AB  - PURPOSE: This study was designed to investigate the effects of P-glycoprotein (P
      gp) expressed in the intestine on the nonlinear pharmacokinetics (PK) of T
      3256336, an inhibitor of apoptosis protein inhibitor, and food effects on its
      bioavailability in rats. METHODS: To investigate the factors that contribute to
      nonlinear PK of T-3256336 in the intestine and liver, rats double-cannulated in
      the portal vein and femoral artery (PS rats) were used. FaFg (Fa, absorption
      ratio; Fg, intestinal availability) and hepatic availability (Fh) were
      simultaneously evaluated based on the difference between the portal and systemic
      blood area under the concentration-time curve (AUC). Elacridar was used as a P-gp
      inhibitor to assess the impact of P-gp on the intestinal absorption. RESULTS:
      After oral administration of T-3256336 to PS rats at 3 and 30 mg/kg, FaFg value
      increased with dose escalation, whereas Fh value was nearly constant. Moreover,
      co-administration of elacridar resulted in a 5-fold increase in the FaFg value at
      3 mg/kg. The AUC value of T-3256336 under fed conditions was 3-fold lower than
      that under fasted conditions. This food effect on the oral bioavailability (BA)
      was reduced by concomitant administration of elacridar. CONCLUSION: P-gp
      expressed in the intestine would cause nonlinear PK and a food effect on BA of T
      3256336 in rats.

PMID- 30105481
TI  - Using Smartphone Crowdsourcing to Redefine Normal and Febrile Temperatures in
      Adults: Results from the Feverprints Study.

PMID- 30105480
TI  - A Meta-Analysis of Universal School-Based Prevention Programs for Anxiety and
      Depression in Children.
AB  - Anxiety and depression are among the most common mental health issues experienced
      in childhood. Implementing school-based prevention programs during childhood,
      rather than adolescence, is thought to provide better mental health outcomes. The
      present meta-analysis aimed to investigate the efficacy of universal school-based
      prevention programs that target both anxiety and depression in children (aged 13
      years or below), and examine three moderators (i.e., program type, primary target
      of program, and number of sessions) on prevention effects. PsycINFO, PubMED, and
      Google Scholar were systematically searched for relevant articles published up to
      and including January 2018. Fourteen randomised controlled trials, consisting of
      5970 children, met eligibility criteria. Prevention programs led to significantly
      fewer depressive symptoms at post-program (g = 0.172) and at long-term follow-up
      periods (g = 0.180), but not at short-term follow-up. Programs were not found to
      prevent anxiety symptoms across any time point. Considerable heterogeneity was
      observed for all effects. Program type and length were found to moderate the
      relationship between prevention program and outcomes. Prevention programs were
      effective in preventing depressive symptoms at post-program and long-term follow
      up, while no significant preventative effect on anxiety symptoms was observed.
      The FRIENDS Program and programs which contained a greater number of sessions
      showed beneficial effects on anxiety and depressive symptoms. Universal programs
      aimed at preventing both anxiety and depression in children are limited. Future
      research should investigate the long-term evaluation of school-based prevention
      programs for anxiety and depression in children.

PMID- 30105482
TI  - Examination of the cellular mechanisms of leukocyte elevation by 10.6 MUm and 650
      nm laser acupuncture-moxibustion.
AB  - To investigate the cell cycle and cellular mechanisms of leukocyte elevation by
      laser acupuncture in rats with cyclophosphamide (CTX)-induced leukopenia. Sixty
      six rats were randomized into six groups: normal, model control group, sham
      treatment group, 10.6 MUm laser treatment group, 650 nm laser treatment group,
      and 10.6 MUm-650 nm compound laser treatment group. Eleven rats were used in the
      normal group and 55 were models that were injected with cyclophosphamide to
      induce leukopenia. For the three laser treatment groups, 10.6-MUm and 650-nm
      lasers, and 10.6-MUm-650-nm compound lasers were used to irradiate the DU14
      (Dazhui) and bilateral ST36 (Zusanli) for 5 min each. The sham laser group
      received the same operation as the laser group but without irradiation. The
      normal group and model group were not treated. Differences in the number of
      nucleated cells in the femoral bone marrow, and cell cycle and cellular apoptosis
      of peripheral leukocytes in rats in various groups were compared. Compared with
      the model group and the sham laser group, the number of nucleated cells in the
      femoral bone marrow in the 10.6-MUm laser, 650-nm laser, and 10.6-MUm-650-nm
      compound laser group was significantly increased after treatment (P = 0.001,
      0.002, 0.034, respectively) and did not show any significant difference with the
      normal group (P = 0.964, P = 0.838, P = 0.287, respectively). The number of cells
      in G2 phase in the 10.6 MUm laser group was similar to that of the normal group
      (P = 0.973). The number of cells in G2 phase in the model, sham, 650-nm laser
      group, and 10.6-MUm-650-nm compound laser group were significantly lower than in
      the normal group and 10.6-MUm laser group (P = 0.016, P = 0.023, P = 0.044, P =
      0.039, respectively). In the model group and the sham treatment group, the
      apoptosis rates of peripheral leukocytes were increased compared with the normal
      group (P = 0.001), while the proportion of cells in the G2 phase was
      significantly lower than in the normal group (P = 0.016), and the proportion of
      cells in S phase was higher than in the normal group (P = 0.014). The incidence
      of apoptosis in peripheral blood cells in the three laser treatment groups did
      not show any statistically significant difference when compared with the normal
      group (P > 0.05). Treatment with the 10.6-MUm, 650-nm, and 10.6-MUm-650-nm
      compound lasers increased the number of nucleated cells in the bone marrow,
      decreased the unfavorable effects of cyclophosphamide on the cell cycle, induced
      the cell cycle towards proliferation, decreased apoptosis, improved the
      intramedullary hematopoietic system, and increased peripheral leukocyte count.

PMID- 30105483
TI  - The impact of Nd: YAG laser posterior capsulotomy by the use of "the circular
      pattern with vitreous strand cut" technique on anterior chamber parameters.
AB  - AIM: The purpose of this study is to identify the effect of Nd: YAG laser
      posterior capsulotomy using an anterior chamber morphology. METHODS: This study
      included 42 eyes of 33 pseudophakic patients with visually significant PCO after
      uncomplicated cataract surgery. Exclusion criteria were complications related to
      cataract surgery, corneal pathology, pseudoexfoliation, glaucoma, uveitis,
      previous ocular surgery or trauma, and posterior segment pathology. All patients
      underwent routine ophthalmic examinations. The AS-OCT measurements were performed
      using NIDEK RS-3000 Lite retinal scan with anterior segment module. The anterior
      chamber depth (ACD) was measured by Monitor A&B Scan biometer. Nd: YAG laser
      posterior capsulotomy was done in a single session by the circular pattern with
      rupture of vitreous strands. Anterior chamber depth (ACD), central corneal
      thickness (CCT), and intraocular pressure (IOP) were measured. Anterior chamber
      angle (ACA), angle opening distances (AOD) at 500 mm (AOD500), AOD at 750 mm
      (AOD750), trabecular-iris space area at 500 (TISA 500), and TISA at 750 (TISA
      750) were measured both nasally and temporally. RESULTS: The mean patient age was
      55.56 +/- 6.33 years. There were non-significant changes in IOP, ACD, and CCT
      with P values 0.395, 0.153, and 0.541, respectively. ACA, AOD500, AOD750, TISA
      500, and TISA 750 highly significantly increased with P value < 0.001 for all.
      CONCLUSION: Nd: YAG laser posterior capsulotomy with the circular pattern with
      vitreous strand cut technique is a safe technique for laser posterior
      capsulotomy.

PMID- 30105484
TI  - Photobiomodulation promotes adenoviral gene transduction in auditory cells.
AB  - Gene therapy is the delivery of a therapeutic gene into target cells to treat
      disorders by replacing disease-causing mutated genes with healthy ones. Gene
      therapy of the inner ear has been recently described, with applications for
      sensorineural hearing loss. However, gene delivery to the location of the inner
      ear, and thus efficacy of therapy, is challenging. Photobiomodulation (PBM) with
      a low-level laser has been suggested to have a therapeutic effect and has the
      potential to augment gene therapy. To investigate whether PBM improves the rate
      of adenovirus (Ad)-mediated viral delivery, we compared low-level laser therapy
      (LLLT) and non-LLLT HEI-OC1 cells treated with an Ad viral vector carrying green
      fluorescent protein (GFP). Cultured HEI-OC1 cells were divided into six groups:
      no treatment control, LLLT only, 1 MUL Ad-GFP, 3 MUL Ad-GFP, 1 MUL Ad-GFP + LLLT,
      and 3 MUL Ad-GFP + LLLT (LLLT: 808 nm at 15 mW for 15 min). Cells were irradiated
      twice: at 2 h and again at 24 h. A nonparametric Mann-Whitney U test was used to
      statistically analyze differences between the control and treatment groups. The
      viral inoculations used in this study did not change the amount of viable HEI-OC1
      cells (N = 4-8). The 1 MUL Ad-GFP + LLLT and 3 MUL Ad-GFP + LLLT groups showed an
      increased density of GFP-positive cells compared to 1 MUL and 3 MUL Ad-GFP cells
      (N = 5-8, 1 MUL: p = 0.0159; 3 MUL: p = 0.0168,). The quantitative analysis of
      the epifluorescence of the 1 MUL Ad-GFP + LLLT, and 3 MUL Ad-GFP + LLLT groups
      revealed increased GFP expression/cell compared to 1 MUL and 3 MUL Ad-GFP cells
      (N = 6-15, 1 MUL: p = 0.0082; 3 MUL: p = 0.0012). The RT-qPCR results were
      consistent (N = 4-5, p = 0.0159). These findings suggest that PBM may enhance the
      gene delivery of Ad-mediated viral transduction, and the combination of the two
      may be a promising tool for gene therapy for sensorineural hearing loss.

PMID- 30105479
TI  - Medicinal Plants with Multiple Effects on Diabetes Mellitus and Its
      Complications: a Systematic Review.
AB  - PURPOSE OF REVIEW: This systematic review describes evidence concerning medicinal
      plants that, in addition to exerting hypoglycemic effects, decrease accompanying
      complications such as nephropathy, neuropathy, retinopathy, hypertension, and/or
      hyperlipidemia among individuals with diabetes mellitus (DM). RECENT FINDINGS:
      Studies on the antidiabetic mechanisms of medicinal plants have shown that most
      of them produce hypoglycemic activity by stimulating insulin secretion,
      augmenting peroxisome proliferator-activated receptors (PPARs), inhibiting alpha
      amylase or alpha-glucosidase, glucagon-like peptide-1 (GLP-1) secretion, advanced
      glycation end product (AGE) formation, free radical scavenging plus antioxidant
      activity (against reactive oxygen or nitrogen species (ROS/RNS)), up-regulating
      or elevating translocation of glucose transporter type 4 (GLUT-4), and preventing
      development of insulin resistance. Not only are medicinal plants effective in DM,
      but many of them also possess a variety of effects on other disease states,
      including the complications of DM. Such plants may be appropriate alternatives or
      adjuncts to available antidiabetic medications.

PMID- 30105485
TI  - Correction of myopic astigmatism by small incision lenticule extraction: does
      laterality matter?
AB  - To evaluate the outcome after astigmatic correction of small incision lenticule
      extraction (SMILE) and to compare the refractive results of right eyes with left
      eyes. Patients who underwent SMILE surgery in our clinic between 2014 and 2016
      (Visumax, Carl Zeiss Meditec, Germany) were retrospectively reviewed.
      Preoperative and postoperative manifest refractions and corrected and uncorrected
      visual acuities were evaluated and changes in refractive astigmatism were
      evaluated by vector analysis. One hundred twenty-one eyes from 82 patients with
      myopic astigmatism were included. The mean preoperative spherical equivalent was 
      6 +/- 1.7 (range from - 9.50 to - 1.25) D and the mean cylinderical power was -
      1.5 +/- 0.6 (range from - 3.75 to - 1.00) D. Postoperatively 71.8% of eyes had <
      0.50 D cylinder magnitude. Vector analysis results based on laterality revealed
      that correction index was 0.87 +/- 0.3 for left eyes and 0.72 +/- 0.3 for right
      eyes (p 0.02). This study revealed that SMILE has favorable astigmatic correction
      affect but left eyes have better outcomes than right eyes.

PMID- 30105487
TI  - ?

PMID- 30105486
TI  - Highly Selective and Sensitive Detection of Hg2+ Based on Forster Resonance
      Energy Transfer between CdSe Quantum Dots and g-C3N4 Nanosheets.
AB  - In the presence of Hg2+, a fluorescence resonance energy transfer (FRET) system
      was constructed between CdSe quantum dots (QDs) (donor) and g-C3N4 (receptors).
      Nanocomposites of g-C3N4 supported by CdSe QDs (CdSe QDs/g-C3N4 nanosheets) were
      fabricated through an electrostatic interaction route in an aqueous solution. The
      nanocomposites were characterized by X-ray photoelectron spectroscopy, X-ray
      diffraction, Fourier-transform infrared spectroscopy, and transmission electron
      microscopy. Results showed that the g-C3N4 nanosheets were decorated randomly by
      CdSe QDs, with average diameter of approximately 7 nm. The feasibility of the
      FRET system as a sensor was demonstrated by Hg (II) detection in water. At pH 7,
      a linear relationship was observed between the fluorescence intensity and the
      concentration of Hg (II) (0-32 nmol/L), with a detection limit of 5.3 nmol/L. The
      new detection method was proven to be sensitive for detecting Hg2+ in water
      solutions. Moreover, the method showed high selectivity for Hg2+ over several
      metal ions, including Na+, Mg2+, Ca2+, Pb2+, Cr3+, Cd2+, Zn2+, and Cu2+. The CdSe
      QDs/g-C3N4 nanosheet conjugate exhibited desirable long-term stability and
      reversibility as a novel FRET sensor. The novel FRET-based fluorescence detection
      provided an attractive assay platform for quantifying Hg2+ in complex water
      solutions.

PMID- 30105488
TI  - Influence of Orally Administered Borneol on the Expression of Hepatic
      Transporters in Rats.
AB  - BACKGROUND AND OBJECTIVE: Borneol, a traditional Chinese medicine (TCM), is often
      orally co-administered with other TCM and chemical drugs, but the drug-drug
      interactions between borneol and the other compounds remains unclear. This work
      investigates the effect of orally administered borneol on the transcription and
      expression of hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4, Oct1,
      Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5) in
      rats, aiming to obtain essential information to guide its clinical applications.
      METHODS: Rats were administered borneol (33, 100 and 300 mg/kg/day, respectively)
      and vehicle (control) orally via intragastric gavage for 7 consecutive days. The
      mRNA levels of rat hepatic uptake transporters (Ntcp, Oatp2b1, Oatp1a1, Oatp1a4,
      Oct1, Oct2, Octn2 and Oat2) and efflux transporters (Mdrla, Mrp2, Mrp4 and Mrp5)
      were determined using real-time quantitative PCR, while the hepatic Ntcp, Mdrla,
      Mrp2, Mrp4 and Mrp5 proteins were quantified using western blotting. RESULTS: The
      oral administration of borneol led to dose-dependent inhibition of mRNA and
      protein expression of Mrp4 and Mdr1a, dose-independent inhibition of mRNA and
      protein expression of Mrp2, and inverse dose-dependent inhibition of mRNA and
      protein expression of Ntcp. No significant effects were observed for mRNA
      expression of the other transporters tested following borneol administration.
      CONCLUSIONS: Oral administration of borneol may affect the metabolism of
      substances that are involved in bile acid enterohepatic circulation and
      substrates of Ntcp, Mdrla, Mrp2 and Mrp4 transporters.

PMID- 30105489
TI  - Leaving gift-giving behind: the ethical status of the human body and transplant
      medicine.
AB  - The paper argues that the idea of gift-giving and its associated imagery, which
      has been founding the ethics of organ transplants since the time of the first
      successful transplants, should be abandoned because it cannot effectively block
      arguments for (regulated) markets in human body parts. The imagery suggests that
      human bodies or their parts are transferable objects which belong to individuals.
      Such imagery is, however, neither a self-evident nor anthropologically
      unproblematic construal of the relation between a human being and their body. The
      paper proposes an alternative conceptualization of that relation, the identity
      view according to which a human being is identical with their living body. This
      view, which offers a new ethical perspective on some central concepts of
      transplant medicine and its ethical and legal standards and institutions,
      supports widely shared intuitive ethical judgments. On this proposal, an act of
      selling a human body or one of its parts is an act of trade in human beings, not
      in owned objects. Transfers of human body parts for treatment purposes are to be
      seen as sharing in another human being's misfortune rather than as giving owned
      objects. From the perspective of policy-making, the proposal requires, first,
      that informed consent for removal of transplant material be obtained from the
      potential benefactor. Secondly, explicit consent by the prospective benefactor is
      obligatory in the case of removal of transplant material from a living
      benefactor. Thirdly, in the case of posthumous retrieval, informed consent by the
      potential benefactor during their life is not ethically indispensable.
      Additionally, while refusal of posthumous retrieval expressed by a potential
      benefactor during their life must be respected, such a refusal needs ethical
      justification and explanation.

PMID- 30105491
TI  - Cystoid macular edema following selective laser trabeculoplasty in a patient with
      ocular hypertension.
AB  - PURPOSE: Presentation of a case with ocular hypertension who developed cystoid
      macular edema (CME) following selective laser trabeculoplasty (SLT). CASE REPORT:
      A 62-year-old male patient who had undergone phacoemulsification surgery for
      traumatic cataract 9 years ago was on ocular hypertension treatment for the last
      5 years. Due to uncontrolled intraocular pressure and side effect of medications,
      a 360 degrees  SLT was performed. The patient returned with decrased visual
      acuity 1 week after the procedure. There was CME in the treated eye. It healed
      completely after topical prednisolone acetate QID and nepafenac QID for 1 week,
      and no recurrence was observed during follow-ups. CONCLUSION: Cystoid macular
      edema may occur following SLT treatment in patients with previous traumatic
      cataract surgery which responds to topical treatment.

PMID- 30105492
TI  - Comment on "performance characteristics of multicolor versus blue light and
      infrared imaging in the identification of reticular pseudodrusen".

PMID- 30105490
TI  - Predicting visual function after an ocular bee sting.
AB  - PURPOSE: To report a case of toxic optic neuropathy caused by an ocular bee
      sting. METHODS: Case report and literature review. RESULTS: A 44-year-old female
      presented with no light perception vision 2 days after a corneal bee sting in her
      right eye. She was found to have diffuse cornea edema with overlying epithelial
      defect and a pinpoint penetrating laceration at 6 o'clock. There was an intense
      green color to the cornea. The pupil was fixed and dilated with an afferent
      pupillary defect. A small hyphema was seen, and a dense white cataract had
      formed. A diagnosis of toxic endophthalmitis with associated toxic optic
      neuropathy was made. The patient underwent pars plana vitrectomy and lensectomy
      with anterior chamber washout. She was also placed on systemic broad-spectrum
      antibiotics. She had noted clinical improvement over the course of her
      hospitalization and was discharged with light perception vision. A corneal
      opacity precluded viewing of the fundus. We utilized ganzfeld electroretinography
      and flash visual evoked potentials (2 and 10 Hz) to assess the visual function.
      Both tests were normal and predicted improvement following restorative surgery.
      She underwent a secondary lens implantation with penetrating keratoplasty 7
      months later. This was followed by an epiretinal membrane peel 1 year after the
      bee sting. Her best corrected visual acuity improved to 20/80. CONCLUSION: Toxic
      endophthalmitis and toxic optic neuropathy can be complications of ocular bee
      sting. We discuss the management of this rare occurrence and the role of
      electroretinographic testing and visual evoked potentials in predicting visual
      outcome.

PMID- 30105494
TI  - Chronic hyponatremia in a patient with renal salt wasting and without cerebral
      disease: relationship between RSW, risk of fractures and cognitive impairment.
AB  - Renal salt wasting syndrome (RSW) is defined as a renal loss of sodium leading to
      hyponatremia and a decrease in extracellular fluid volume (ECV). Differentiation
      of this disorder from the syndrome of inappropriate antidiuretic hormone
      secretion (SIADH), a common cause of hyponatremia, can be difficult because both
      can present with hyponatremia and concentrated urine with natriuresis. Our
      clinical case about a 78-year-old woman with a recent fracture of the right femur
      not only confirms that this syndrome can occur in patients without intracranial
      pathologies (CT documented), but depicts how the hyponatremia caused by RSW can
      show a chronic, oscillating course. This is an interesting point of view because
      it suggests to us to consider RSW in the differential diagnosis of patients with
      chronic hyponatremia.

PMID- 30105493
TI  - Subjectively different but objectively the same? Three profiles of QoL in people
      with severe mental health problems.
AB  - PURPOSE: Quality of life (QoL) is a broad outcome that is often used to assess
      the impact of treatment and care interventions in mental health services. QoL,
      however, is known to be influenced by individual values and preferences. To
      investigate this heterogeneity on the individual level, this study aimed to
      distinguish classes with distinct QoL profiles in a broad group of people with
      severe mental health problems and to identify the QoL domains that are most
      strongly related to the classes. METHODS: QoL data of seven studies that used the
      Lancashire quality of life profile (LQoLP) were used in a latent class analysis.
      Sociodemographic variables, health-related variables, and measures of well-being
      were used to characterise the classes. Additionally, univariate entropy scores
      were used to assess the strength of the association between the ten LQoLP domains
      and the latent classes. RESULTS: Two of the three indices of fit pointed towards
      a three-class model. The three classes differed significantly on all of the LQoLP
      domains, on well-being, and on 'being in an intimate relationship'. No
      differences were found for the majority of the health-related and
      sociodemographic variables. The LQoLP domains 'family relations', 'positive self
      esteem', and 'negative self-esteem' were most strongly related to the latent
      classes. CONCLUSIONS: The identification of three distinct classes of QoL scores
      re-emphasises the heterogenic nature of QoL. The lack of differences in
      sociodemographic or health-related characteristics between the three classes
      suggests that QoL is primarily determined by subjective, personal evaluations,
      rather than by objective characteristics and circumstances.

PMID- 30105495
TI  - Analysis of water sports injuries admitted to a pediatric trauma center: a 13
      year experience.
AB  - BACKGROUND: Unintentional injury is the leading cause of death in children and
      adolescents. Injuries occurring during boating and recreational water sports are
      poorly described in the literature. Herein, we compare injuries from water sports
      to those resulting from motor vehicle collisions, which are better described in
      existing literature. METHODS: A retrospective review of 1935 consecutive
      pediatric trauma patients, as defined by age < 18 years, admitted to a single
      level-1 pediatric trauma center between January 2000 and August 2013 was
      performed. Patients were divided into two cohorts based on the mechanism of
      injury: water sports injury (WSI) or motor vehicle collision (MVC). Demographics,
      injury descriptors, and outcomes were reviewed for each patient. Categorical
      variables were compared by Chi square or Fisher's exact test, and continuous by t
      test or Mann-Whitney U test. Parametric data are reported as mean +/- standard
      deviation and nonparametric as median (interquartile range). Significance was set
      at alpha level 0.05. RESULTS: A total of 18 pediatric patients were admitted for
      WSI and 615 for MVC during the study period. Among those with WSI, mean age was
      12 +/- 4 years, mean Injury Severity Score (ISS) was 11 +/- 10, and mean Revised
      Trauma Score (RTS) was 7.841(IQR 6.055-7.841). 44% of WSI occurred by personal
      watercraft (Jet Ski, WaveRunner), 39% by boat, and 17% by other means (e.g.,
      diving, tubing, kite surfing). Overall, the most common WSI included skin/soft
      tissue lacerations (59%), head injury/concussion (33%), tendon/ligament
      lacerations (28%), and extremity fractures (28%). Compared to 615 patients
      admitted for MVC, age, sex, race, Glasgow Coma Scale, ISS, RTS, spleen and liver
      laceration rates, neurosurgical consultation, ICU admission, ICU and total length
      of stay, and mortality were similar. Patients with WSI were more likely to be
      tourists (44% vs. 5%, p < 0.001). Those with WSI showed a significantly higher
      requirement for any surgical intervention (61% vs. 15%, p = 0.001). The rate of
      open fracture (28% vs. 6%, p = 0.006) and, subsequently, orthopedic procedures
      (39% vs. 17%, p = 0.027) were also higher in the WSI group. CONCLUSION: Overall,
      water sports injuries are similar in in-hospital mortality to motor vehicle
      collisions. They are more likely to result in penetrating trauma and more likely
      to require surgical intervention. Primary and secondary prevention strategies
      should specifically target personal watercraft usage and tourist populations.

PMID- 30105496
TI  - Gastroesophageal reflux in children with neurological impairment: a systematic
      review and meta-analysis.
AB  - Neurologically impaired children (NIC) suffer severe gastroesophageal reflux
      (GER) with poor fundoplication outcome. Aims of the study were: (1) to determine
      the recurrence of GER after fundoplication in NIC; (2) to compare fundoplication
      versus gastro-jejunal tube feeding insertion (GJ) and fundoplication versus total
      esophagogastric dissociation (TEGD) in primarily treating GER in NIC. Using
      defined search strategy, two investigators identified all comparative studies
      reporting the mentioned procedures to primarily treat GER in NIC. The study was
      conducted under PRISMA guidelines. The meta-analysis was performed using RevMan
      5.3. Data are mean +/- SD. Of 3840 titles/abstracts screened, 14 studies on
      fundoplication (2716 pts.) reported a recurrence/persistence of GER higher in NIC
      (14.2 +/- 8.3%) than in neurologically normal (9.4 +/- 5.2%; p = 0.0001), with an
      increased incidence of re-do fundoplication (12.6 +/- 7.0% versus 9.1 +/- 4.5%; p
      < 0.01). Three studies revealed a similar risk of undergoing subsequent
      fundoplication after GJ (4.9 +/- 2.1%) or initial fundoplication (12.0 +/- 0.6%;
      p = ns). Four studies showed a lower recurrence of GER following TEGD (1.4 +/-
      1.1%) than fundoplication (24.8 +/- 1.4%; p = 0.002). NIC are at risk of
      recurrence/persistence of GER after fundoplication or GJ. TEGD seems more
      effective to primarily treat GER in NIC. Prospective randomized controlled trials
      are necessary to establish which is the ideal treatment of GER in NIC.

PMID- 30105497
TI  - Optimization of Ciprofloxacin Hydrochloride Spray-Dried Microparticles for
      Pulmonary Delivery Using Design of Experiments.
AB  - Ciprofloxacin is a broad-spectrum antibiotic for treatment of pulmonary diseases
      such as chronic obstructive pulmonary disease and cystic fibrosis. The purpose of
      this work was to rationally study the spray drying of ciprofloxacin in order to
      identify the formulation and operating conditions that lead to a product with
      aerodynamic properties appropriate for dry powder inhalation. A 24 - 1 fractional
      factorial design was applied to investigate the effect of selected variables
      (i.e., ciprofloxacin hydrochloride (CIP) concentration, drying air inlet
      temperature, feed flow rate, and atomization air flow rate) on several product
      and process parameters (i.e., particle size, aerodynamic diameter, moisture
      content, densities, porosity, powder flowability, outlet temperature, and process
      yield) and to determine an optimal condition. The studied factors had a
      significant effect on the evaluated responses (higher p value 0.0017), except for
      the moisture content (p value > 0.05). The optimal formulation and operating
      conditions were as follows: CIP concentration 10 mg/mL, drying air inlet
      temperature 110 degrees C, feed volumetric flow rate 3.0 mL/min, and atomization
      air volumetric flow rate 473 L/h. The product obtained under this set had a
      particle size that guarantees access to the lung, a moisture content acceptable
      for dry powder inhalation, fair flowability, and high process yield. The PDRX and
      SEM analysis of the optimal product showed a crystalline structure and round and
      dimpled particles. Moreover, the product was obtained by a simple and green spray
      drying method.

PMID- 30105499
TI  - Non-surgical endodontic management of immature permanent mandibular first molar:
      a 3 year follow-up.
AB  - BACKGROUND: Deep carious lesions in immature permanent molars with pulp necrosis
      pose a serious challenge to contemporary paedodontic practice. A further complex
      clinical scenario is an immature permanent molar with varying root formation in
      both roots. This case report demonstrates the successful management of an
      immature permanent mandibular first molar. CASE REPORT: An 8-year-old boy was
      referred for endodontic management of 36 by a general practitioner. After
      clinical and radiographic evaluation, a diagnosis of recurrent chronic periapical
      abscess with abrupt root closure in the mesial root and cessation of root closure
      in the distal root was made. Apexification was undertaken in three appointments.
      In the first appointment, under local analgesia and isolation, the mesial canals
      were prepared to size #F3 with rotary Protaper Universal and the distal canal was
      left unprepared. Both canals were irrigated with 5% sodium hypochlorite and
      calcium hydroxide intracanal medicament was placed. One week later, the mesial
      canals were obturated and a 4 mm white MTA apical plug was placed in the distal
      canal. Partial extrusion of the MTA was seen periapically. After 24 h, the hard
      setting of the MTA plug was verified, remainder of the distal canal was obturated
      and core filling was placed followed by a preformed metal crown as an
      intermediate restoration. FOLLOW-UP: The patient was asymptomatic and showed
      resolution of the lesion, normal thickness of the PDL space with continuity of
      the lamina dura after 12 months. Extruded MTA was partially resorbed. Three years
      follow-up showed complete resorption of the extruded MTA and an intact lamina
      dura.

PMID- 30105498
TI  - A pulse of summer precipitation after the dry season triggers changes in
      ectomycorrhizal formation, diversity, and community composition in a
      Mediterranean forest in California, USA.
AB  - Rapid responses of microbial biomass and community composition following a
      precipitation event have been reported for soil bacteria and fungi, but
      measurements characterizing ectomycorrhizal fungi remain limited. The response of
      ectomycorrhizal fungi after a precipitation event is crucial to understanding
      biogeochemical cycles and plant nutrition. Here, we examined changes in
      ectomycorrhizal formation, diversity, and community composition at the end of a
      summer drought and following precipitation events in a conifer-oak mixed forest
      under a semiarid, Mediterranean-type climate in CA, USA. To study the effects of
      different amounts of precipitation, a water addition treatment was also
      undertaken. Ectomycorrhizal fungal diversity and community composition changed
      within 6 days following precipitation, with increased simultaneous mortality and
      re-growth. Ectomycorrhizal diversity increased and community composition changed
      both in the natural rainfall (less than 10 mm) and water addition (50 mm)
      treatments, but larger decreases in ectomycorrhizal diversity were observed from
      9 to 16 days after precipitation in the water addition treatment. The changes
      were primarily a shift in richness and abundance of Basidiomycota species,
      indicating higher drought sensitivity of Basidiomycota species compared with
      Ascomycota species. Our results indicate that ectomycorrhizal formation,
      diversity, and community composition rapidly respond to both precipitation events
      and to the amount of precipitation. These changes affect ecosystem functions,
      such as nutrient cycling, decomposition, and plant nutrient uptake, in semiarid
      regions.

PMID- 30105500
TI  - A star-shaped DNA probe based on strand displacement for universal and
      multiplexed fluorometric detection of genetic variations.
AB  - A star-shaped fluorescent DNA probe (S-probe) is described that can recognize
      target DNA and discriminate it from interfering DNA via strand displacement
      including branch migration and toehold exchange. The artificially designed S
      probe does not harm the strand displacement while it allows the fluorescently
      labelled strand and the quencher-labelled strand to be shared among different S
      probes targeting different genetic variations. Generally, multiplexed detection
      of different MT/WT pairs requires different fluorophore-labelled and quencher
      labelled strands. The two labelled oligonucleotides of S-probe have sequences
      decoupled from the target/interfering DNA sequence, so the same fluorescent and
      quencher strands can be used for different S-probes that target different
      sequences. The sensitivity, specificity, and general applicability of the method
      toward BRCA 41293497 mutation, KRAS G13D mutation and two types of EGFR mutations
      (T790 M and L858R) were experimentally demonstrated. The limit of quantification
      of the MT concentration is 2 nM, and the detection limit of the low abundance of
      the target sequence is 5% (40 nM of MT strand in the background of 760 nM of WT
      strand). The fluorometric assay with excitation/emission wavelengths of 485/582
      nm was successfully applied to clinical samples spiked with mutant-type and wild
      type DNA. The unique structure of the S-probe provides a useful tool for the
      regulation of the strand displacement reaction. Conceivably, the star-shaped DNA
      probe can be widely adopted to multiplexed detection of genetic variations and
      provide novel insights into the regulation of strand displacement processes as
      utilized in DNA based nanomachines. Graphical abstract A star-shaped fluorescent
      DNA probe (S-probe) with a detection limit of 2 nM was adopted to multiplexed
      detection of genetic variations via strand displacement including branch
      migration and toehold exchange.

PMID- 30105501
TI  - Alice in Wonderland syndrome: a novel neurological presentation of Zika virus
      infection.
AB  - Zika virus (ZIKV) is a flavivirus endemic in Africa and Southern Asian countries,
      which has recently emerged in unprecedented epidemic proportions around the
      world. Although ZIKV infection is often asymptomatic or distinguished by non
      specific influenza-like symptoms, an increase in its pathogenicity and biological
      behavior has been the hallmark of the current pandemic. Increasing evidence
      suggests that neurotropic strains of ZIKV have evolved from less pathogenic
      strains of the virus. Neurological manifestations of ZIKV infection include a
      spectrum of congenital and non-congenital clinical entities, however visual
      somatosensory perceptual disorders have not been recorded to date. Herein, we
      report a case of a 15-year-old female who presented with a constellation of
      perceptual symptoms (metamorphopsia, telopsia, and pelopsia) following acute ZIKV
      infection. Although such symptoms may have originated from direct viral injury, a
      post-ZIKV autoimmune reaction to previously unexposed neuronal surface antigens
      or through molecular mimicry cannot be excluded. The development of Alice in
      Wonderland syndrome in our patient highlights the ever-increasing expanding
      spectrum of neurological symptoms associated to ZIKV infection.

PMID- 30105504
TI  - Comparative Genomics of Nitrogen Cycling Pathways in Bacteria and Archaea.
AB  - Despite the explosion of metagenomic sequencing data, using -omics data to
      predict environmental biogeochemistry remains a challenge. One or a few genes
      (referred to as marker genes) in a metabolic pathway of interest in meta-omic
      data are typically used to represent the prevalence of a biogeochemical reaction.
      This approach often fails to demonstrate a consistent relationship between gene
      abundance and an ecosystem process rate. One reason this may occur is if a marker
      gene is not a good representative of a complete pathway. Here, we map the
      presence of 11 nitrogen (N)-cycling pathways in over 6000 complete bacterial and
      archaeal genomes using the Integrated Microbial Genomes database. Incomplete N
      cycling pathways occurred in 39% of surveyed archaeal and bacterial species
      revealing a weakness in current marker-gene analyses. Furthermore, we found that
      most organisms have limited ability to utilize inorganic N in multiple oxidation
      states. This suggests that inter-organism exchange of inorganic N compounds is
      common, highlighting the importance of both community composition and spatial
      structure in determining the extent of recycling versus loss in an ecosystem.

PMID- 30105503
TI  - [What motivates patients with atopic diseases to search the internet-a focus
      group study on expectations and demands].
AB  - BACKGROUND: People affected by allergies with mild-to-moderate symptoms are often
      not treated adequately, despite the availability of prevention and self-therapy
      measures. Given their good and quick accessibility when seeking information,
      evidence- and web-based services that are user-friendly may strengthen a more
      independent way of handling an allergy and may also increase health literacy. In
      order for such services to be found and read, developers and providers need to
      know about information needs, demands and users' behavior. OBJECTIVES: On which
      occasions does the target group search for allergy-specific information? Which
      preferences and demands do affected persons have regarding a web-based service?
      MATERIALS AND METHODS: Three individual interviews and four focus groups with 37
      participants (19-81 years; hay fever, n = 30; asthma, n = 17; eczema, n = 15)
      were conducted in four German cities. These were recorded and transcribed
      verbatim. A multiprofessional team developed a system for coding the texts (two
      independent encoders, MAXQDA analysis software). RESULTS: Those who are affected
      usually seek information only in case of a concrete need for action. Impulses
      are, among others, symptoms, suggestions from the social environment, the
      beginning of the allergy season or an allergy-related contact with the health
      system. A web-based service should primarily include information about treatment
      options, provide individualized support for everyday life action strategies, and
      promote adequate self-management skills. DISCUSSION: In order to promote self
      management skills, a web-based service should focus on allergy symptoms,
      treatment options and day-to-day help.

PMID- 30105502
TI  - Neurofilament light chain in blood is negatively associated with
      neuropsychological performance in HIV-infected adults and declines with
      initiation of antiretroviral therapy.
AB  - HIV-associated neurocognitive disorder (HAND) persists in the combination
      antiretroviral therapy (cART) era and is associated with diminished quality of
      life. The disorder remains challenging to diagnose given the requirement for
      comprehensive neuropsychological testing. Blood biomarkers are needed to
      facilitate the diagnosis of HAND and to gauge neurological response to
      antiretroviral therapy. We performed a study of plasma neurofilament light chain
      (NFL) that included 37 HIV-infected and 54 HIV-negative adults. In the univariate
      mixed-effect model involving HIV-infected participants, there was a statistically
      significant linear relationship between composite neuropsychological score (NPT
      11) and plasma NFL (slope = - 9.9, standard error = 3.0 with 95% confidence
      interval - 3.2 to - 16.6 and p = 0.008 when testing slope = 0). Similarly, in the
      multivariate mixed-effect model, higher plasma NFL was significantly associated
      with worse NPT-11 (slope = - 11.5, standard error = 3.3 with 95% confidence
      interval - 3.7 to - 19.0 and p = 0.01 when testing slope = 0). The association
      between NPT-11 and NFL appeared to be driven by the group of individuals off
      cART. In a subset of participants who had visits before and after 24 weeks on
      cART (n = 11), plasma NFL declined over time (median = 22.7 versus 13.4 pg/ml, p
      = 0.02). In contrast, plasma NFL tended to increase over time among HIV-negative
      participants (median 10.3 versus 12.6 pg/ml, p = 0.065, n = 54). Plasma NFL
      therefore shows promise as a marker of neuropsychological performance during HIV.
      Larger studies are needed to determine if NFL could serve as a diagnostic tool
      for HAND during suppressive cART.

PMID- 30105505
TI  - The Hidden World of Rickettsiales Symbionts: "Candidatus Spectririckettsia
      obscura," a Novel Bacterium Found in Brazilian and Indian Paramecium caudatum.
AB  - Symbioses between bacteria and eukaryotes are widespread and may have significant
      impact on the evolutionary history of symbiotic partners. The order Rickettsiales
      is a lineage of intracellular Alphaproteobacteria characterized by an obligate
      association with a wide range of eukaryotic hosts, including several unicellular
      organisms, such as ciliates and amoebas. In this work, we characterized the
      Rickettsiales symbionts associated with two different genotypes of the freshwater
      ciliate Paramecium caudatum originated from freshwater environments in distant
      geographical areas. Phylogenetic analyses based on 16S rRNA gene showed that the
      two symbionts are closely related to each other (99.4% identity), belong to the
      family Rickettsiaceae, but are far-related with respect to previously
      characterized Rickettsiales. Consequently, they were assigned to a new species of
      a novel genus, namely "Candidatus Spectririckettsia obscura." Screening on a
      database of short reads from 16S rRNA gene amplicon-based profiling studies
      confirmed that bacterial sequences related to the new symbiont are preferentially
      retrieved from freshwater environments, apparently with extremely scarce
      occurrence (< 0.1% positive samples). The present work provides new information
      on the still under-explored biodiversity of Rickettsiales, in particular those
      associated to ciliate host cells.

PMID- 30105506
TI  - Bacterial Diversity in Replicated Hydrogen Sulfide-Rich Streams.
AB  - Extreme environments typically require costly adaptations for survival, an
      attribute that often translates to an elevated influence of habitat conditions on
      biotic communities. Microbes, primarily bacteria, are successful colonizers of
      extreme environments worldwide, yet in many instances, the interplay between
      harsh conditions, dispersal, and microbial biogeography remains unclear. This
      lack of clarity is particularly true for habitats where extreme temperature is
      not the overarching stressor, highlighting a need for studies that focus on the
      role other primary stressors (e.g., toxicants) play in shaping biogeographic
      patterns. In this study, we leveraged a naturally paired stream system in
      southern Mexico to explore how elevated hydrogen sulfide (H2S) influences
      microbial diversity. We sequenced a portion of the 16S rRNA gene using bacterial
      primers for water sampled from three geographically proximate pairings of streams
      with high (> 20 MUM) or low (~ 0 MUM) H2S concentrations. After exploring
      bacterial diversity within and among sites, we compared our results to a previous
      study of macroinvertebrates and fish for the same sites. By spanning multiple
      organismal groups, we were able to illuminate how H2S may differentially affect
      biodiversity. The presence of elevated H2S had no effect on overall bacterial
      diversity (p = 0.21), a large effect on community composition (25.8% of variation
      explained, p < 0.0001), and variable influence depending upon the group-whether
      fish, macroinvertebrates, or bacteria-being considered. For bacterial diversity,
      we recovered nine abundant operational taxonomic units (OTUs) that comprised a
      core H2S-rich stream microbiome in the region. Many H2S-associated OTUs were
      members of the Epsilonproteobacteria and Gammaproteobacteria, which both have
      been implicated in endosymbiotic relationships between sulfur-oxidizing bacteria
      and eukaryotes, suggesting the potential for symbioses that remain to be
      discovered in these habitats.

PMID- 30105507
TI  - Food insecurity, sexual risk taking, and sexual victimization in Ghanaian
      adolescents and young South African adults.
AB  - OBJECTIVES: The objectives of this study were to examine whether food insecurity
      is associated with sexual risk taking and victimization in young people (aged 16
      24); and to investigate whether the relationship of food insecurity with sexual
      risk taking and victimization is moderated by gender. METHODS: Cross-sectional
      data were obtained in 2014 from a sample of Ghanaian adolescents (n = 773) and in
      2015 from young South African adults (n = 823). We used multilevel logistic
      regression given the study's binary outcome and clustered data. We tested a
      moderation effect of gender by including an interaction between gender and food
      insecurity. RESULTS: Food insecurity was highly prevalent (72% in Ghana and 83%
      in South Africa). Food insecurity was significantly associated with unwanted
      sexual contact among Ghanaian adolescents (OR 1.05, 95% CI 1.02, 1.08) and age
      disparate sex among young South African adults (OR 1.03, 95% CI 1.00, 1.06).
      Results indicated no moderating effect of gender. CONCLUSIONS: Our findings
      underscore the importance of food access on young people's sexual health,
      regardless of gender. Prevention efforts may be more relevant when integrated
      with food security interventions that target vulnerable adolescents and young
      adults, irrespective of gender.

PMID- 30105508
TI  - Correction to: Portal Vein Embolization Utilizing N-Butyl Cyanoacrylate for
      Contralateral Lobe Hypertrophy Prior to Liver Resection: A Systematic Review and
      Meta-Analysis.
AB  - The following publication was cited in the published article, but it was not
      included in the reference list.

PMID- 30105509
TI  - Improving the Specificity of PSA Screening with Serum and Urine Markers.
AB  - PURPOSE OF REVIEW: Prostate cancer remains a significant public health burden. In
      order to decrease the morbidity and mortality associated with prostate cancer,
      serum prostate-specific antigen (PSA) screening has been used since the 1990s.
      However, there is concern for overdiagnosis of prostate cancer with widespread
      PSA screening, which could lead to overtreatment and its attendant morbidities.
      RECENT FINDINGS: In order to avoid unnecessary biopsy and downstream effects
      including treatment of insignificant prostate cancer, a number of tests have been
      proposed to improve upon PSA screening. Increasing the specificity of prostate
      cancer screening above that of PSA testing should reduce the incidence of
      unnecessary prostate biopsy. However, an increase in specificity is associated
      with a decrease in sensitivity, so these tests must be balanced with the concern
      for missing the diagnosis of potentially significant disease. In this context, we
      present a review of six common biomarkers proposed to improve the specificity of
      prostate cancer screening-free PSA, prostate health index, 4Kscore, PCA3, Select
      MDx, and ExoDx Prostate(Intelliscore).

PMID- 30105510
TI  - A randomized controlled trial of lusutrombopag in Japanese patients with chronic
      liver disease undergoing radiofrequency ablation.
AB  - BACKGROUND: Thrombocytopenia represents an obstacle for invasive procedures in
      chronic liver disease (CLD) patients. We aimed to estimate the appropriate dose
      and evaluate the efficacy and safety of lusutrombopag for the treatment of
      thrombocytopenia before percutaneous liver radiofrequency ablation (RFA) for
      primary hepatic cancer in patients with CLD. METHODS: In this multicenter,
      randomized, double-blind, placebo-controlled study conducted in Japan, 61 CLD
      patients with platelet count < 50 * 103/uL at screening were randomized to
      placebo or lusutrombopag 2, 3, or 4 mg once daily for 7 days, followed by a 28
      day post-treatment assessment period. The primary efficacy endpoint was the
      proportion of patients who did not require platelet transfusion before RFA. The
      pre-specified key secondary efficacy endpoint was the proportion of responders.
      Adverse events (AEs) and thrombosis-related AEs were evaluated. RESULTS: The
      proportion of patients who did not require platelet transfusion before RFA and
      that of responders were significantly higher (p < 0.01) in the 2-mg (80.0,
      66.7%), 3-mg (81.3, 68.8%), and 4-mg groups (93.3, 80.0%) compared with the
      placebo group (20.0, 6.7%) and showed a dose-dependent effect. The incidence of
      AEs was 97.8 and 100% in the lusutrombopag (all groups) and placebo groups,
      respectively; no dose-related increase was observed. Four patients experienced
      thrombosis-related events (one each in the placebo and 2-mg groups, and two in
      the 4-mg group). A total of 16 (18%) adverse drug reactions occurred in the
      safety analysis set. CONCLUSIONS: Lusutrombopag 3 mg once daily for 7 days was
      effective without raising concerns about excessive increases in platelet count.
      CLINICAL TRIAL REGISTRATION: The study is registered at JapicCTI-121944.

PMID- 30105511
TI  - Hiatal hernia involving prolapse of the entire stomach into the mediastinum after
      distal gastrectomy: a case report.
AB  - BACKGROUND: Prolapse of a small part of the proximal stomach through the hiatus
      into the mediastinum is relatively common. Hiatal hernia involving the
      postoperative stomach has been reported previously, but the degree of hernia was
      not so severe, and hiatal hernia involving the prolapse of the entire stomach
      following gastrectomy into the mediastinum has never been reported. We describe a
      very rare case of large hiatal hernia involving the entire postoperative stomach.
      CASE PRESENTATION: A 79-year-old man with a history of distal gastrectomy for
      submucosal benign tumor 40 years ago was referred to our hospital because of
      dysphagia and weight loss. Computed tomography revealed prolapse of the entire
      postoperative stomach into the mediastinum, and a radical operation was
      performed. There was a strong adhesion in the hernial sac of the mediastinum, but
      only little adhesion due to a previous open surgery in the abdominal cavity was
      present. After the stomach was pulled into the abdominal cavity, suture
      cruroplasty and Toupet fundoplication without dissection of the short gastric
      artery were performed. The patient experienced postoperative paralytic ileus, but
      the rest of the postoperative course was uneventful and the symptom of dysphagia
      improved. CONCLUSIONS: We presented a very rare large hiatal hernia involving the
      entire postoperative stomach. Toupet fundoplication preserving the short gastric
      artery could be one of the optimal surgeries to prevent postoperative
      regurgitation of the remnant stomach.

PMID- 30105512
TI  - Middle East observational study in metastatic soft tissue sarcoma: an
      epidemiological study on the treatment patterns (MOON).
AB  - PURPOSE: Soft tissue sarcomas (STS) are a heterogeneous group of rare mesenchymal
      neoplasms, accounting for < 1% of all newly diagnosed malignancies. These tumors
      can occur in almost any anatomic site though they most frequently occur in the
      extremities. The objective of the study was to describe the epidemiology,
      treatment paradigm, and real-world outcomes in the clinical management of
      metastatic STS (mSTS) in the Middle East and North Africa (MEA) region. METHODS:
      MOON was an observational, multicenter, retrospective patient chart review study
      which included 200 patients with mSTS in the final analysis. The primary
      objective of the study is exploratory, so it is presented using descriptive
      statistics. RESULTS: At the time of presentation, 62.0% patients had metastatic
      disease, 27.5% had received only their primary diagnosis and 10.0% had
      experienced a local recurrence. The most frequent STS localizations were lower
      extremities (74%), trunk (28.5%) and upper extremities (10.5%). Primary tumor was
      staged as T2b in the majority (60%) of patients. Surgical treatment was performed
      most often for the primary disease, whereas radiation therapy and chemotherapy
      were predominantly administered with palliative intent. A total of 38 patients
      received treatment with pazopanib. Thirteen adverse events (AEs) were attributed
      to pazopanib in eight patients. CONCLUSION: Adult patients treated for STS have
      al most equal gender ratio and mostly are middle aged. The majority of patients
      have metastatic disease and disease progression, and half of the patients died
      from the disease during the period of evaluation. This study obtained real-life
      data on the clinical management of STS in MEA countries which could be shared
      with the medical community.

PMID- 30105514
TI  - Understanding "What Could Be": A Call for 'Experimental Behavioral Genetics'.
AB  - Behavioral genetic (BG) research has yielded many important discoveries about the
      origins of human behavior, but offers little insight into how we might improve
      outcomes. We posit that this gap in our knowledge base stems in part from the
      epidemiologic nature of BG research questions. Namely, BG studies focus on
      understanding etiology as it currently exists, rather than etiology in
      environments that could exist but do not as of yet (e.g., etiology following an
      intervention). Put another way, they focus exclusively on the etiology of "what
      is" rather than "what could be". The current paper discusses various aspects of
      this field-wide methodological reality, and offers a way to overcome it by
      demonstrating how behavioral geneticists can incorporate an experimental approach
      into their work. We outline an ongoing study that embeds a randomized
      intervention within a twin design, connecting "what is" and "what could be" for
      the first time. We then lay out a more general framework for a new field
      experimental BGs-which has the potential to advance both scientific inquiry and
      related philosophical discussions.

PMID- 30105515
TI  - Maternal Knowledge and Unsafe Baby Sleep Position: A Cross-Sectional Survey in
      Southern Brazil.
AB  - Objective to evaluate women's knowledge about the best baby sleeping position and
      to identify factors associated with a greater probability of putting infants to
      sleep in an unsafe position, in Rio Grande, Southern Brazil. Method This is a
      cross-sectional population-based study that included all women who bore children
      in 2013 in this municipality. A single, standardized questionnaire was given
      within 48 h after delivery in the only two local maternity hospitals. The outcome
      was that women reported the lateral and the ventral decubitus as the best
      sleeping positions for babies. A Chi square test was used for proportions and
      Poisson regression was used with robust variance adjustment in the multivariate
      analysis. The prevalence ratio was the measure of effect used. Results We
      included 2624 women in this study. Of these, 82.1% (95% CI 80.6-83.6) stated that
      the baby should sleep in the lateral or ventral decubitus positions. 76.4%
      reported having acquired this knowledge from their mothers and 34.7% were willing
      to adopt the correct (supine) sleeping position for their child if recommended by
      doctors. The adjusted analysis showed that the lower the schooling of the mothers
      and the greater the number of people per bedroom and number of children, the
      greater the probability of women choosing an unsafe baby sleeping position.
      Conclusions for Practice This study showed that the percentage of women who are
      unaware of the correct baby sleeping position is very high, that doctors should
      be convinced to recommend the supine baby sleeping position, and that campaigns
      on this subject should also include grandparents as a priority intervention
      group.

PMID- 30105513
TI  - Prognostic value of histone marks H3K27me3 and H3K9me3 and modifying enzymes
      EZH2, SETDB1 and LSD-1 in colorectal cancer.
AB  - PURPOSE: Studies on the performance of epigenetic-based biomarkers in colorectal
      cancer (CRC) are scarce and have shown contradictory results. Thus, we sought to
      examine the prognostic value of histone-modifying enzymes (EZH2, SETDB1 and LSD
      1) and histone post-translational marks (H3K27me3 and H3K9me3) in CRC. METHODS: A
      retrospective series of 207 CRC patients primarily submitted to surgery in a
      cancer center was included in this study. Clinicopathological data were
      retrieved. One representative paraffin block per case was selected for
      immunohistochemistry, including normal and CRC tissues whenever possible. The
      percentage of positive nuclear staining (digital image analysis) was used to
      classify patients into "low" and "high" expression groups for each biomarker.
      Correlations between immunoexpression levels, clinicopathological features and
      clinical outcomes [disease-specific (DSS) and disease-free (DFS) survival] were
      examined. Statistical significance was set at p < 0.05. RESULTS: CRC tissues
      showed significantly lower expression of SETDB1 and higher expression of the
      remainder four biomarkers compared to normal mucosa. High EZH2 expression
      correlated with disease recurrence/progression, whereas low LSD1 expression and
      high H3K9me3 and H3K27me3 expression were associated with more advanced stage. In
      multivariable analysis, cases with high LSD1 expression displayed significantly
      better DSS and DFS (HR 0.477, 95% confidence interval: 0.247-0.923) adjusted for
      pathological TNM stage. CONCLUSION: EZH2, SETDB1, LSD1, H3K9me3 and H3K27me3
      expression are altered in CRC and may play a role in colorectal carcinogenesis.
      LSD1 immunoexpression levels independently predicted patient outcome in this
      cohort. Further investigations, using larger series, are warranted to confirm its
      potential clinical value and unravel underlying molecular mechanisms.

PMID- 30105517
TI  - [High pain expectation and impairment from pre-existing pain are risk factors for
      severe postoperative pain : Results of a study using the Lubeck Pain Risk
      Questionnaire].
AB  - BACKGROUND: The intensity of postoperative pain is characterized by large
      interindividual variability. Furthermore, strong postoperative pain is known to
      influence physical recovery after surgery. High (preoperative) pain expectation
      and pre-existing pain, which are associated with pain-related disability
      (impairing pain) are risk factors for strong postoperative pain. They can be
      determined with the Lubeck Pain Risk Questionnaire used for the first time in
      this study. The aim of this study was to explore the hypothesis that patients
      with a combination of the characteristics (1) preoperative impairing pain and (2)
      high pain expectation are more likely to have strong postoperative pain. Patients
      with these characteristics represent a unique group of patients and are more
      likely to develop distinct postoperative pain and can therefore be characterized
      as a risk group. MATERIAL AND METHODS: A total of 501 patients at the departments
      of general surgery, plastic surgery, trauma surgery and orthopedic surgery of the
      UKSH Campus Lubeck were included in this study. All underwent elective surgery.
      Study patients were 18 years and older. Those needing postoperative treatment in
      an intensive care unit were excluded from this study (n = 18). The
      characteristics "preoperative pain" and "pain expectation" were measured with the
      Lubeck Pain Risk Questionnaire the day before surgery. The primary outcome
      variable was the average postoperative pain intensity, which was measured with a
      numeric rating scale (NRS 0-10) and scores > 4 were defined as severe pain.
      RESULTS: The NRS range for "preoperative pain" was subdivided as follows: "no
      pain" (NRS = 0), "functional pain" (NRS = 1-3), and "impairing pain" (NRS = 4
      10); that for "pain expectation" as: "low expectation" (NRS = 0-4) and "high
      expectation" (NRS = 5-10). To determine these cut-off points, they were varied
      from > 1 to > 8 and those with highest effect size for strong postoperative pain
      were chosen. Patients with a high pain expectation had significantly stronger
      postoperative pain (p < 0.001) and significantly more often higher pain intensity
      than patients with a low expectation (53.3% vs. 20.6%, respectively, p < 0.001).
      Patients with pre-existing impairing pain had significantly stronger and more
      frequently higher postoperative pain than patients with pre-existing functional
      pain (43.4% vs. 18.4%, p < 0.05). Patients with a combination of the factors
      "preoperative impairing pain" and "high pain expectation" showed distinct
      postoperative pain with NRS > 4 significantly more often (59.4%, p < 0.001).
      These findings could be demonstrated for the departments general surgery, plastic
      surgery and trauma surgery. CONCLUSION: The combination of both risk factors
      results in a unique risk group for the appearance of strong postoperative pain.
      This group can be economically determined in the daily clinical routine using the
      Lubeck Pain Risk Questionnaire. Further studies must be carried out to show if
      additional perioperative procedures can be profitable for the risk group
      identified with the Lubeck Pain Risk Questionnaire; however, patients falling
      outside the risk group must not be neglected because they too can develop severe
      postoperative pain.

PMID- 30105518
TI  - [Perspectives for anesthesiologists in hospital hygiene].
AB  - BACKGROUND: It is mandatory for hospitals in Germany to employ infection control
      physicians and have an external consultation. The recommended coverage has
      substantially increased in the last years. Typically, infection control
      physicians are specialists for hygiene and environmental medicine and/or for
      microbiology. As there is already a shortage of these specialists, a curricular
      educational program in infection control was developed by the German Medical
      Association in 2011. This program addresses specialists of different clinical
      disciplines. It covers a period of 24 months and includes 200 h of courses,
      divided into 6 modules. In addition, 7 weeks of internships must be absolved in
      hospital hygiene, in a microbiological laboratory and in the public health
      service. During the program, the trainee must be accompanied by a qualified
      supervisor, who is a specialist in hygiene. The aim of this article is to
      describe the current status of this program. METHODS: A total of 91 infection
      control physicians, organized in different networks, were invited by email to
      take part in a survey with the online tool Survey Monkey (San Mateo, USA). The
      questions in the survey aimed at the characteristics of the participants as well
      as the conditions of the program. Further information about the various general
      regulations and conditions of the course was gathered through internet research,
      and from telephone and email contact with the State Medical Associations.
      RESULTS: Approximately 250 physicians completed the program between 2011 and
      2017. The graduates were mostly anesthesiologists (45%) and 81% had a leading
      position (consultant or higher) before beginning the program. Most of them also
      had further education in antibiotic stewardship and/or infectious diseases. The
      requirements regarding training hours, examination and certification varied
      between the State Medical Associations. The supervision, a mandatory part of the
      program, is also implemented differently from state to state. Of the participants
      49% felt well-qualified for the challenges ahead after finishing this program.
      DISCUSSION: The program was able to increase the number of infection control
      physicians in a relatively short period of time; however, to guarantee a
      comparable quality of education it is necessary to standardize the requirements
      on a national level. The supervision also needs to be further specified. A new
      program is currently being developed by the German Medical Association, which
      will hopefully lead to an improvement of the educational program. Special
      strengths of the new infection control physicians are the broad clinical
      experience as well as the additional qualifications in antibiotic stewardship
      and/or infectious diseases. The weaknesses are the lack of practical experience
      and knowledge of technical hygiene. A mandatory inclusion of antibiotic
      stewardship and infectious diseases in the program would increase its impact.
      Anesthesiologists are well-suited for training as infection control physicians.
      For them, a new, exciting field of activity has opened up with the chance to be
      the head of their own department.

PMID- 30105519
TI  - On the occasion of the retirement of Marc Regenmortel as Editor-in-Chief of
      Archives of Virology.

PMID- 30105516
TI  - [Systematic analysis of airway registries in emergency medicine].
AB  - BACKGROUND: A myriad of publications have contributed to an evidence-based
      approach to airway management in emergency services and admissions in recent
      years; however, it remains unclear which international registries on airway
      management in emergency medicine currently exist and how they are characterized
      concerning inclusion criteria, patient characteristics and definition of
      complications. METHODS: A systematic literature research was carried out in
      PubMed with respect to publications from 2007-2017. All publications from airway
      registries collecting data on prehospital or emergency department (ED) airway
      management were included. Publications from pediatric intensive care units (PICU)
      were also included as long as they were the primary place of pediatric emergency
      care. RESULTS: A total of eleven emergency airway registries (EAR) were
      identified that were primarily concerned with airway management. Furthermore,
      reported data on emergency airway management were extracted from different,
      national resuscitation registries. There was only one multinational EAR which
      exclusively collects data on pediatric emergency airway management (NEAR4KIDS,
      National Emergency Airway Registry for Kids). Additionally, all emergency
      department airway registries identified include data on pediatric emergency
      airway management to varying degrees (0.2-10.5%). Published observation periods
      were also highly variable with a minimum of 18 months and a maximum of 156
      months. The ANZEDAR (Australia and New Zealand Emergency Airway Registry) is
      currently the largest EAR with data from 43 participating institutions in 2
      different countries, while the NEAR III (National Emergency Airway Registry)
      includes data on 21,374 emergency intubations over a 10-year period and thus has
      the largest number of emergency interventions. Reported rapid sequence induction
      (RSI) rates in the registries are between 27.5% and 100%. First-pass success
      rates vary between 69% and 89%, while the reported use of video laryngoscopy is 0
      73%. CONCLUSION: This study identified eleven EARs that sometimes widely differed
      concerning inclusion periods, inclusion criteria, definition of complications and
      application of newer methods of emergency airway management. Thus, comparability
      of the reported results and first-pass success rates is only possible to a
      limited extent. The authors therefore advocate the initiation of an airway
      registry in emergency medicine in German-speaking countries.

PMID- 30105520
TI  - Columbid circoviruses detected in free ranging pigeons from Southern Brazil:
      insights on PiCV evolution.
AB  - Pigeon circovirus (PiCV) is taxonomically classified as a member of the
      Circovirus genus, family Circoviridae. The virus contains a single stranded DNA
      genome of approximately 2 kb, with minor length variations among different
      isolates. The occurrence of PiCV infections in pigeons (Columba livia) has been
      documented worldwide over the past 20 years; however, in Brazil there were still
      no reports on PiCV detection. This study identifies seven PiCV genomes recovered
      from domestic pigeons of South Brazil through high-throughput sequencing and
      shows a high frequency of PiCV infection, through quantitative real-time PCR.
      Phylogenetic classification was performed by maximum likelihood analysis of the
      full genomes, ORF V1 (Rep) and ORF C1 (Cap). The results show that either full
      genome or Cap based analysis allowed PiCV classification into five major clades
      (groups A to E), where Brazilian sequences were classified as A, C or D.
      Recombination analyses were carried out with Simplot and RDP4 and the results
      show that both Rep and Cap ORFs contain several recombination hotspots, pointing
      to an important role for such events in PiCV evolution.

PMID- 30105522
TI  - Hepatocellular Carcinoma with Orbital Metastasis: a Unique Multidisciplinary Case
      Report.

PMID- 30105521
TI  - Combined Early and Late [68Ga]PSMA-HBED-CC PET Scans Improve Lesion Detectability
      in Biochemical Recurrence of Prostate Cancer with Low PSA Levels.
AB  - PURPOSE: Our aim was to evaluate the benefit of early (1 h post-injection (p.i.))
      and late (3 h p.i.) [68Ga]PSMA-HBED-CC positron emission tomography (PET)/x-ray
      computed tomography (CT) imaging for detection of biochemical recurrence (BCR) of
      prostate cancer (PCa). PROCEDURES: Seventy patients with BCR of the PCa and
      prostate-specific antigen (PSA) levels of less than 2.0 MUg/l were subjected to
      [68Ga]PSMA-HBED-CC PET (mean injected activity 180 MBq). While early imaging
      contained whole body scans, late imaging was confined to the pelvis and the lower
      abdomen. Uptake in suspicious lesions was analyzed by peak and maximum
      standardized uptake values (SUVpeak/max). Tumor-to-background ratios were
      calculated for all lesions in which the liver served as reference organ. The
      Wilcoxon matched-pair signed-rank test was used to compare the uptake in
      suspicious lesions between early and late imaging. Follow-up data were used to
      validate the existence of the additionally detected lesions. RESULTS: Forty-four
      of the 70 patients thus examined were interpreted as PSMA-positive in early
      and/or late scans while 26 remained without suspicion of PSMA tracer uptake. A
      total of 70 suspicious lesions were analyzed. Ten tumor-suspicious lesions from
      seven different patients were better or exclusively visible in the late
      measurements while three tumor-suspicious lesions from three different patients
      were better or exclusively visible in the early images. A validation by follow-up
      data was possible for 11 of these 13 additionally detected lesions. In direct
      comparison between early and late imaging, the mean SUVmax in PSMA-positive
      lesions was 74 % higher (p < 0.001) and the mean SUVpeak was 36 % higher (p =
      0.001) in the late scans. The SUVmean in the reference regions was decreasing in
      the late measurements, whereas the mean TBR increased by a factor of 3 (p <
      0.001). Taking confirmed lesions only into account, we estimated a 10 % gain in
      additionally detected PSMA-positive lesions (7/70) within the patient cohort.
      CONCLUSIONS: The time period between injection and data acquisition influences
      the detection rate of [68Ga]PSMA-HBED-CC PET/CT. In biochemical recurrence with
      low PSA levels, late [68Ga]PSMA-HBED-CC PET/CT imaging offers frequent advantages
      with regard to lesion contrast.

PMID- 30105523
TI  - Impact of Prior Malignancy on Survival Outcomes of Stage IV Pancreatic
      Adenocarcinoma: SEER-Based Cohort.
AB  - PURPOSE: Pancreatic cancer is one of the most fatal malignancies and the fourth
      leading cause of cancer-related mortality in the USA. Most clinical trials
      involving pancreatic adenocarcinoma (PAC) patients exclude subjects with a prior
      malignancy because of the possible effect of prior malignancies on survival.
      However, no data in the medical literature support this assumption. In this
      paper, we aim to study the impact of having a prior malignancy on the survival
      outcomes of stage IV PAC. METHODS: We used the surveillance, epidemiology, and
      end results database to review patients with stage IV PAC diagnosed between 1973
      and 2014. We calculated overall and pancreatic cancer-specific survival of these
      patients using unadjusted Kaplan-Meier test and multivariable covariate-adjusted
      Cox models. RESULTS: We reviewed 66,874 stage IV PAC patients, of which 4942 had
      a prior malignancy. Kaplan-Meier and Cox models showed that a history of prior
      malignancy did not cause significant difference in overall survival (HR = 0.938,
      95%CI = 0.880-1.000, p = .052). However, a prior malignancy was associated with a
      better pancreatic cancer-specific survival (HR = 0.855, 95% CI = 0.796-0.918, p <
      .001). CONCLUSION: A prior malignancy before stage IV PAC was not associated with
      worse survival outcomes. Researchers should take these results into consideration
      when including/excluding patients to improve the generalizability and accuracy of
      their results.

PMID- 30105524
TI  - Intraoral voice recording-towards a new smartphone-based method for vocal
      rehabilitation.
AB  - After laryngectomy, a new voice is needed. We present the first steps in the
      development of a smartphone-based method. A microphone is placed in the mouth to
      record the pseudo-whispering voice of laryngectomized patients. This recording is
      analyzed by voice recognition software followed by voice synthesis. Eventually,
      this will be performed on a smartphone. We placed a microphone at 10 different
      places inside and outside the mouth (two in front of the mouth (at 2 and 20 cm),
      five on the palate and three on the lower jaw) and made voice recordings in eight
      healthy men. These recordings were analyzed by voice recognition software. The
      text generated by the software was compared with the original text. Over all
      positions, the correct detection of words recorded in the mouth was 19.3% vs.
      75.2% (p = 0.01) outside the mouth. In the mouth, recording taken on the maxilla
      (22.8%) was much better than on the mandible (13.5%) (p = 0.01). The optimum
      position for a microphone on the maxilla was at the highest point of the palate
      with 31.9% correct word identification there (p = 0.028). Further investigations
      have to be undertaken with forthcoming development of smartphone processing power
      and with development of a smartphone-based voice recognition application.

PMID- 30105525
TI  - Comparison Between Fluorescent Probe and Ion-Selective Electrode Methods for
      Intracellular pH Determination in Leuconostoc mesenteroides.
AB  - The intracellular pH (pHin) of Leuconostoc mesenteroides subsp. mesenteroides 19D
      was evaluated by two different methods, fluorescent probe and ion-selective
      electrode. Two fluorescent probes 5 (and-6)-carboxyfluorescein diacetate
      succinimidyl ester (cFDASE) and 5 (and-6)-carboxy-2',7'-dichlorofluorescein
      diacetate succinimidyl ester (cDCFDASE) were tested to evaluate the intracellular
      pH (pHin) of living cells at a medium pH (pHex) ranged from 5.0 to 6.5. Salicylic
      acid was used as a probe for the ion-selective electrode method. Cells kept 60
      80% of cFDASE probe at all pHex values against 5-10% of cDCFDASE probe at pHex <=
      6.0. The pHin values measured by the ion-selective electrode were higher by 0.1
      0.6 pH units at pHex ranged from 5.0 to 6.5 than those determinated by
      fluorescent probe method. The possibility to study the intracellular pH at a wide
      external pH range using a single probe, and the simplicity of the material and
      experimental protocol may make the ion-selective electrode method most useful and
      easy to measure the intracellular pH of lactic acid bacteria compared with the
      other techniques like fluorescent probes.

PMID- 30105527
TI  - Cladribine Tablets: A Review in Relapsing MS.
AB  - Cladribine is a deoxyadenosine analogue prodrug that preferentially depletes
      lymphocytes, key cells underlying multiple sclerosis (MS) pathogenesis.
      Cladribine tablets (Mavenclad(r)) represent the first short-course oral disease
      modifying drug (DMD) for use in MS. The tablets, administered in two short
      courses 1 year apart, are indicated for the treatment of adults with highly
      active relapsing MS on the basis of data from pivotal clinical trials, including
      the phase 3 study CLARITY and its extension. A cumulative cladribine tablets dose
      of 3.5 mg/kg administered in this fashion in CLARITY reduced clinical relapse,
      disability progression and MRI-assessed disease activity and also improved some
      aspects of health-related quality of life (HR-QOL) versus placebo over 96 weeks
      in adults with relapsing-remitting MS (RRMS). Moreover, in the 96-week extension
      (plus 24 weeks' supplemental follow-up), no additional clinical benefit was
      gained from continuing versus discontinuing cladribine tablets after the first
      two annual courses of therapy, although MRI activity was more notable in a subset
      of cladribine tablet recipients who discontinued the drug. In post hoc analyses
      of CLARITY and/or a phase 2b trial, benefits of cladribine tablets were seen in
      patients with high disease activity (HDA) relapsing MS that were sometimes
      greater than in patients without HDA. Cladribine tablets have an acceptable
      tolerability profile and do not appear to be associated with an increased risk of
      overall infection or with an increased risk of malignancy (vs. matched reference
      populations). Active comparisons and longer-term follow-up would be beneficial,
      although current data indicate that for adults with highly active relapsing MS,
      cladribine tablets are an effective treatment option with the convenience of low
      burden, short-course, oral administration.

PMID- 30105529
TI  - Benefits of using a self-expandable metallic stent as a bridge to surgery for
      right- and left-sided obstructive colorectal cancers.
AB  - PURPOSE: To assess the benefit of placing a self-expandable metallic stent (SEMS)
      as a bridge to surgery for obstructive colorectal cancer (OCRC) according to the
      tumor site. METHODS: The subjects of this retrospective multicenter cohort study
      were 201 patients with OCRC, but without initial bowel perforation, who were
      treated either with a self-expandable metallic stent (SEMS) as a bridge to
      surgery (n = 109) or with primary surgery (PS; n = 92) between 2014 and 2016. The
      cohort consisted of 68 patients with right-sided and 133 left-sided OCRC. We
      evaluated the short-term surgical outcomes for each side. RESULTS: The SEMS group
      of patients with left-sided OCRC had significantly higher rates of primary
      resection, primary resection with anastomosis, stoma-free surgery, and
      laparoscopic surgery than the PS group of patients with left-sided OCRC. In
      contrast, the SEMS group of patients with right-sided OCRC had only a
      significantly higher rate of laparoscopic surgery than the PS group of patients
      with right-sided OCRC, but they had a longer overall hospital stay. There were no
      significant differences between the two treatment groups in the rates of
      morbidity or mortality, for either right-sided or left-sided OCRC. CONCLUSION:
      The benefit of a SEMS as a bridge to surgery may be less for right-sided than for
      left-sided obstructions in colon cancer patients.

PMID- 30105530
TI  - Towards personalised positive psychiatry? : Commentary on "Vantage sensitivity: a
      framework for individual differences in response to psychological intervention".

PMID- 30105526
TI  - Bioreducible Poly(Amino Ethers) Based mTOR siRNA Delivery for Lung Cancer.
AB  - PURPOSE: Lung cancer is one of the leading causes of deaths in the United States,
      but currently available therapies for lung cancer are associated with reduced
      efficacy and adverse side effects. Small interfering RNA (siRNA) can knock down
      the expression of specific genes and result in therapeutic efficacy in lung
      cancer. Recently, mTOR siRNA has been shown to induce apoptosis in NSCLC cell
      lines but its use is limited due to poor stability in biological conditions.
      METHODS: In this study, we modified an aminoglyocisde-derived cationic poly
      (amino-ether) by introducing a thiol group using Traut's reagent to generate a
      bio-reducible modified-poly (amino-ether) (mPAE). The mPAE polymer was used to
      encapsulate mTOR siRNA by nanoprecipitation method, resulting in the formation of
      stable and bio-reducible nanoparticles (NPs) which possessed an average diameter
      of 114 nm and a surface charge of approximately +27 mV. RESULTS: The mTOR siRNA
      showed increased release from the mTS-mPAE NPs in the presence of 10 mM
      glutathione (GSH). The polymeric mTS-mPAE-NPs were also capable of efficient gene
      knockdown (60 and 64%) in A549 and H460 lung cancer cells, respectively without
      significant cytotoxicity at 30 MUg/ml concentrations. The NPs also showed time
      dependent cellular uptake for up to 24 h as determined using flow cytometry.
      Delivery of the siRNA using these NPs also resulted in significant inhibition of
      A549 and H460 cell proliferation in vitro, respectively. CONCLUSIONS: The results
      demonstrate that the mPAE polymer based NPs show strong potential for siRNA
      delivery to lung cancer cells. It is anticipated that future modification can
      help improve the efficacy of nucleic acid delivery, leading to higher inhibition
      of lung cancer growth in vitro and in vivo.

PMID- 30105531
TI  - Single-port laparoscopic-assisted resection for a large abdominal cystic
      lymphangioma: a case report.
AB  - BACKGROUND: We report the case of a young woman with a large abdominal cystic
      lymphangioma that was successfully resected using single-port laparoscopic
      assisted cystectomy. This avoided the need for a large surgical incision, as
      would result during conventional laparotomy. CASE PRESENTATION: A 17-year-old
      young woman was admitted to our hospital complaining of abdominal pain that had
      persisted for 3 days. Computed tomography revealed a 10 * 10 * 10-cm low-density
      area in the mid-abdomen, and magnetic resonance imaging showed a large abdominal
      cystic lesion. A mesenteric cyst was suspected, and single-port laparoscopic
      assisted resection was performed. The cyst fluid was aspirated using a tissue
      adhesive, a suction tube with negative pressure, and a 16-gage over-the-needle
      catheter and syringe. The tumor size was reduced without any spillage of cyst
      fluid into the abdominal cavity. Then, the shrunken cystic tumor was successfully
      removed via the small wound and resected outside the abdomen. Pathological
      findings revealed an abdominal cystic lymphangioma derived from the greater
      omentum. CONCLUSIONS: Our procedure was easy to perform and required no special
      materials. Therefore, it could be applied to various cases, such as for abdominal
      cystic diseases.

PMID- 30105533
TI  - Chemotion-ELN part 2: adaption of an embedded Ketcher editor to advanced research
      applications.
AB  - The Ketcher editor, available as an Open Source software package for drawing
      chemical structures, has been expanded to include several features that allow
      storage, management and application of templates, as well as the use of symbols
      for a planning and processing of solid phase synthesis. In addition, tools for
      the drawing of coordinative bonds to represent e.g. organometallic compounds were
      added. The editor has been implemented into an Electronic Lab Notebook (ELN)
      application which enables the use of the Ketcher editor for advanced operations
      in chemistry research. The developments of the ELN-integrated Ketcher (ketcher
      rails) support the retrieval of identifiers and structure-related information
      from external databases and the molecule-based calculation of analytical values.
      The reworked editor can be used to generate molecular structures in reaction
      templates and to generate syntheses plans.

PMID- 30105532
TI  - Actinomycetes: an unexplored microorganisms for plant growth promotion and
      biocontrol in vegetable crops.
AB  - Actinomycetes, a Gram positive bacteria, well reported as a source of
      antibiotics, also possess potential to control various plant pathogens, besides
      acting as plant growth promoting agent. Chemicals in different forms are
      extensively being used in vegetable farming, adversely affecting the environment
      and consumer health. Microbial agent like actinomycetes can substantially replace
      these harmful chemicals, and have now started finding a place as an important
      input in to farming practices. Only selected vegetable crops belonging to 11
      different families have been explored with use of actinomycetes as biocontrol and
      plant growth promoting agent till now. It provides ample opportunities to
      vegetable researchers, to further explore with use of this very important group
      of microorganisms, in order to achieve even higher production level of safe
      vegetables. Mycostop and Actinovate are two actinomycetes based formulations
      globally available for use in vegetable farming as a substitute for chemical
      formulations. Present review article has summarized the literature available on
      use of actinomycetes in vegetable farming. Existing wide gap in knowledge, and
      potential thrust areas for future research have also been projected.

PMID- 30105528
TI  - Social Skills Deficits in Autism Spectrum Disorder: Potential Biological Origins
      and Progress in Developing Therapeutic Agents.
AB  - Autism spectrum disorder is defined by two core symptoms: a deficit in social
      communication and the presence of repetitive behaviors and/or restricted
      interests. Currently, there is no US Food and Drug Administration-approved drug
      for these core symptoms. This article reviews the biological origins of the
      social function deficit associated with autism spectrum disorder and the drug
      therapies with the potential to treat this deficit. A review of the history of
      autism demonstrates that a deficit in social interaction has been the defining
      feature of the concept of autism from its conception. Abnormalities identified in
      early social skill development and an overview of the pathophysiology
      abnormalities associated with autism spectrum disorder are discussed as are the
      abnormalities in brain circuits associated with the social function deficit.
      Previous and ongoing clinical trials examining agents that have the potential to
      improve social deficits associated with autism spectrum disorder are discussed in
      detail. This discussion reveals that agents such as oxytocin and propranolol are
      particularly promising and undergoing active investigation, while other agents
      such as vasopressin agonists and antagonists are being activity investigated but
      have limited published evidence at this time. In addition, agents such as
      bumetanide and manipulation of the enteric microbiome using microbiota transfer
      therapy appear to have promising effects on core autism spectrum disorder
      symptoms including social function. Other pertinent issues associated with
      developing treatments in autism spectrum disorder, such as disease heterogeneity,
      high placebo response rates, trial design, and the most appropriate way of
      assessing effects on social skills (outcome measures), are also discussed.

PMID- 30105534
TI  - [New developements in endovascular infrarenal aortic aneurysm treatment].
AB  - CLINICAL/METHODICAL ISSUE: New technical developments in endovascular aortic
      repair (EVAR) have broadened the range of patients eligible for minimally
      invasive aneurysm treatment. Optimization of delivery sheaths and catheters by
      considerable downsizing of diameters, increase of pushability and stability
      combined with flexibility are important parameters. PERFORMANCE: Especially
      patients characterized by small and tortuous iliac access vessels can nowadays be
      treated by EVAR. Ease and effectiveness of applicability guarantee safety and
      quality improvement, which results in better treatment of patients. Progress in
      stent-graft design with integrated options for repositioning, active positioning
      and aneurysm sealing facilitate treatment of angulated vessel segments or
      hitherto unsuitable sealing zones. PRACTICAL RECOMMENDATIONS: Interventionalists
      have to be familiar with all available stent-graft materials and techniques.
      Profound knowledge helps to choose the best material for a patient's individual
      anatomy, confident application and long-term satisfactory results.

PMID- 30105536
TI  - Erratum to: Feasibility of the lifestyle integrated functional exercise concept
      in cognitively impaired geriatric rehabilitation patients.
AB  - Erratum to: Z Gerontol Geriat (2018) https://doi.org/10.1007/s00391-018-1431-7 In
      the online version of this article the following acknowledgement was
      missing:"This study was supported by a doctoral scholarship from the Robert Bosch
      Foundation (RBS). The content is solely the responsibility of the ....

PMID- 30105535
TI  - [Assessment of ligament and tendon injuries of the elbow using magnetic resonance
      imaging].
AB  - An overview about the normal anatomy and frequent pathologies of tendons and
      ligaments of the elbow using MRI will be provided. The unique joint configuration
      and articulation, as well as passive ligamentous and active muscle structures as
      well as the unique configuration of the articulating components of the elbow
      contribute to joint stabilization. MRI is an essential imaging modality in
      patients with ligamentous injuries including the sequelae of joint dislocation as
      well as chronic pathologies such as long-standing and refractory tendinopathies.
      Ideally, when reporting MRI of the elbow, the joint is separated into its four
      compartments, anterior, posterior, medial and lateral, allowing precise,
      comprehensive and structured reporting.

PMID- 30105537
TI  - Intimate Partner Violence and Help-Seeking Behaviour: A Systematic Review of
      Cross-Cultural Differences.
AB  - Intimate partner violence (IPV) is an issue that affects women across all
      cultures. It is essential to understand how women could be assisted to prevent
      and reduce the effects of violence. This systematic review examined studies that
      made cross-cultural comparisons of differences in help-seeking behaviour of women
      who have experienced IPV. Databases including the Cochrane Library, PsychInfo and
      others were searched for literature published between 1988 and 2016. Seventeen
      articles with a total of 40,904 participants met the inclusion criteria. This
      review found some differences in the procurement of support across cultural
      groups. While Caucasian women were more likely to seek assistance from formal
      services such as mental health and social services, Latina/Hispanic and African
      American women were more likely to utilize other types of formal supports such as
      hospital and law enforcement services. The findings regarding utilization of
      informal support systems showed mixed results. Overall, the findings of this
      systematic review suggest that women from culturally diverse minority backgrounds
      should be educated and encouraged to access support before and after experiencing
      IPV. Further, potential barriers to help-seeking need to be identified and
      addressed across women from all cultures.

PMID- 30105538
TI  - Heterogeneous blood flow in microvessels with applications to nanodrug transport
      and mass transfer into tumor tissue.
AB  - Nanodrug transport in tumor microvasculature and deposition/extravasation into
      tumor tissue are an important link in the nanodrug delivery process. Considering
      heterogeneous blood flow, such a dual process is numerically studied. The
      hematocrit distribution is solved by directly considering the forces experienced
      by the red blood cells (RBCs), i.e., the wall lift force and the random cell
      collision force. Using a straight microvessel as a test bed, validated computer
      simulations are performed to determine blood flow characteristics as well as the
      resulting nanodrug distribution and extravasation. The results confirm that RBCs
      migrate away from the vessel wall, leaving a cell-free layer (CFL). Nanodrug
      particles tend to preferentially accumulate in the CFL, leading to increased
      concentration near the endothelial surface layer. However, shear-induced NP
      diffusion is diminished within the CFL, causing to a much slower lateral
      transport rate into tumor tissue. These competing effects determine the NP
      deposition/extravasation rates. The present modeling framework and NP flux
      results provide new physical insight. The analysis can be readily extended to
      simulations of NP transport in blood microvessels of actual tumors.

PMID- 30105539
TI  - Sperm lipidic profiles differ significantly between ejaculates resulting in
      pregnancy or not following intracytoplasmic sperm injection.
AB  - Although assisted reproduction techniques involve the use of semen samples, there
      is little scientific methodology applied when selecting sperm. To select the most
      appropriate spermatozoa, first we need to define the optimal molecular
      characteristics. Sperm lipids may contribute to sperm function, thus our aim was
      to compare the lipidic profiles of sperm samples used in intracytoplasmic sperm
      injection cycles that ultimately led to a pregnancy with those that did
      not.Spermatozoa from infertile patients after intracytoplasmic sperm injection
      (group non-pregnant, n = 16; vs. group pregnant, n = 22) were analyzed for lipid
      composition using ultra-high performance liquid chromatography coupled to mass
      spectrometry, by means two platforms for measuring fatty acyls, bile-acids,
      lysoglycerophospholipids, glycerolipids, cholesteryl-esters, sphingolipids, and
      glycerophospholipids. Lipid levels were compared using a univariate test and
      multivariate analyses after logarithmic transformation.We detected 151 different
      lipids in the sperm samples, 10 of which were significantly increased in sperm
      samples from the NP group, ranging from 1.10- to 1.30-fold change. These were
      primarily ceramides, sphingomyelins and three glycerophospholipids, a
      lysophosphatidylcholine, and two plasmalogen species. Additionally, 2
      Monoacylglycerophosphocholine were also found in higher levels in non-pregnant
      group.Our results describe the composition of sperm lipids linked to optimal
      sperm function, opening new possibilities for the development of male fertility
      diagnostic tools and culture media formulations to improve sperm quality and
      enhance reproductive results. Given that lipids compose the majority of the sperm
      plasma membrane, this information is also useful in designing new sperm selection
      tools that will allow for the selection of the best spermatozoa.

PMID- 30105540
TI  - Toxicity of Water-Accommodated Fractions (WAF), Chemically Enhanced WAF (CEWAF)
      of Oman Crude Oil and Dispersant to Early-Life Stages of Zebrafish (Danio rerio).
AB  - This study focused on comparing the lethal and sublethal toxicity of water
      accommodated fractions (WAF) and chemically enhanced WAF (CEWAF) of crude oil to
      zebrafish (Danio rerio) on early life stages (ELS). Results showed that the
      addition of GM-2 dispersant caused an increase in the levels of total petroleum
      hydrocarbons (TPHs) and total priority polycyclic aromatic hydrocarbons
      (SigmaPAHs). Based on SigmaPAHs, the LC20 estimates for WAF and CEWAF were 4.88
      ug L-1 and 1.19 ug L-1, respectively, indicating that CEWAF was approximately
      four times more toxic. CEWAF exposure caused markedly lower hatching rates and
      higher malformation frequencies than WAF. Meanwhile, the general morphology score
      (GMS) values in CEWAF were about fourfold lower than that in WAF, indicating that
      CEWAF exposure induced more significant developmental delay. The results
      suggested that chemical dispersant enhanced the toxicity of crude oil to
      zebrafish on ELS and its application could increase the exposure of fishes to
      crude oil.

PMID- 30105541
TI  - Allosteric inhibition site of transglutaminase 2 is unveiled in the N terminus.
AB  - Previously we have demonstrated transglutaminase 2 (TGase 2) inhibition abrogated
      renal cell carcinoma (RCC) using GK921 (3-(phenylethynyl)-2-(2-(pyridin-2
      yl)ethoxy)pyrido[3,2-b]pyrazine), although the mechanism of TGase 2 inhibition
      remains unsolved. Recently, we found that the increase of TGase 2 expression is
      required for p53 depletion in RCC by transporting the TGase 2 (1-139 a.a)-p53
      complex to the autophagosome, through TGase 2 (472-687 a.a) binding p62. In this
      study, mass analysis revealed that GK921 bound to the N terminus of TGase 2 (81
      116 a.a), which stabilized p53 by blocking TGase 2 binding. This suggests that
      RCC survival can be stopped by p53-induced cell death through blocking the p53
      TGase 2 complex formation using GK921. Although GK921 does not bind to the active
      site of TGase 2, GK921 binding to the N terminus of TGase 2 also inactivated
      TGase 2 activity through acceleration of non-covalent self-polymerization of
      TGase 2 via conformational change. This suggests that TGase 2 has an allosteric
      binding site (81-116 a.a) which changes the conformation of TGase 2 enough to
      accelerate inactivation through self-polymer formation.

PMID- 30105542
TI  - Coated and Hollow Microneedle-Mediated Intradermal Immunization in Mice with
      Diphtheria Toxoid Loaded Mesoporous Silica Nanoparticles.
AB  - PURPOSE: To examine the immunogenicity of diphtheria toxoid (DT) loaded
      mesoporous silica nanoparticles (MSNs) after coated and hollow microneedle
      mediated intradermal immunization in mice. METHODS: DT was loaded into MSNs and
      the nanoparticle surface was coated with a lipid bilayer (LB-MSN-DT). To prepare
      coated microneedles, alternating layers of negatively charged LB-MSN-DT and
      positively charged N-trimethyl chitosan (TMC) were coated onto pH-sensitive
      microneedle arrays via a layer-by-layer approach. Microneedle arrays coated with
      5 or 3 layers of LB-MSN-DT were used to immunize mice and the elicited antibody
      responses were compared with those induced by hollow microneedle-injected liquid
      formulation of LB-MSN-DT. Liquid DT formulation with and without TMC (DT/TMC)
      injected by a hollow microneedle were used as controls. RESULTS: LB-MSN-DT had an
      average size of about 670 nm and a zeta potential of -35 mV. The encapsulation
      efficiency of DT in the nanoparticles was 77%. The amount of nano-encapsulated DT
      coated onto the microneedle array increased linearly with increasing number of
      the coating layers. Nano-encapsulated DT induced stronger immune responses than
      DT solution when delivered intradermally via hollow microneedles, but not when
      delivered via coated microneedles. CONCLUSION: Both the nano-encapsulation of DT
      and the type of microneedles affect the immunogenicity of the antigen.

PMID- 30105543
TI  - Simultaneous voltammetric detection of 5-hydroxyindole-3-acetic acid and 5
      hydroxytryptamine using a glassy carbon electrode modified with conducting
      polymer and platinised carbon nanofibers.
AB  - The authors describe a method for simultaneous voltammetric determination of 5
      hydroxytryptamine (serotonin; 5-HT) and its metabolite 5-hydroxyindoleacetic acid
      (5-HIAA). A glassy carbon electrode was modified with poly(pyrrole-3-carboxylic
      acid) and with platinised carbon nanofibers to obtain a sensor that can quantify
      5-HT and 5-HIAA with detection limits of 10 nM and 20 nM, respectively. The peak
      currents, best measured at voltages of 170 mV and 500 mV (vs. Ag/AgCl) for 5-HT
      and 5-HIAA, increase linearly in the 0.01-100 MUM concentration range for both
      analytes. The method was successfully applied to the quantitation of 5-HT and 5
      HIAA in spiked artificial urine samples, and the sensor can be used up to 10
      days. Graphical abstract A new electroanalytical device was developed for
      separation and quantitation of 5-hydroxytryptamine (5-HT) and 5-hydroxyindole-3
      acetic acid (5-HIAA), based on stripping square wave voltammetry, exploiting
      conducting polymer surfaces on platinised carbon nanofiber supports.

PMID- 30105544
TI  - Intracerebral EEG Artifact Identification Using Convolutional Neural Networks.
AB  - Manual and semi-automatic identification of artifacts and unwanted physiological
      signals in large intracerebral electroencephalographic (iEEG) recordings is time
      consuming and inaccurate. To date, unsupervised methods to accurately detect iEEG
      artifacts are not available. This study introduces a novel machine-learning
      approach for detection of artifacts in iEEG signals in clinically controlled
      conditions using convolutional neural networks (CNN) and benchmarks the method's
      performance against expert annotations. The method was trained and tested on data
      obtained from St Anne's University Hospital (Brno, Czech Republic) and validated
      on data from Mayo Clinic (Rochester, Minnesota, U.S.A). We show that the proposed
      technique can be used as a generalized model for iEEG artifact detection.
      Moreover, a transfer learning process might be used for retraining of the
      generalized version to form a data-specific model. The generalized model can be
      efficiently retrained for use with different EEG acquisition systems and noise
      environments. The generalized and specialized model F1 scores on the testing
      dataset were 0.81 and 0.96, respectively. The CNN model provides faster, more
      objective, and more reproducible iEEG artifact detection compared to manual
      approaches.

PMID- 30105545
TI  - Reactive Blue 4 as a Single Colorimetric Chemosensor for Sequential Determination
      of Multiple Analytes with Different Optical Responses in Aqueous Media: Cu2+
      Cysteine Using a Metal Ion Displacement and Cu2+-Arginine Through the Host-Guest
      Interaction.
AB  - In the current study, we reported a novel label-free and facile colorimetric
      approach for the sequential detection of copper ion (Cu2+), L-arginine (Arg), and
      L-cysteine (Cys) in the H2O (10.0 mmol L-1 HEPES buffer solution, pH 7.0) using
      Reactive Blue 4 (RB4). First, the presence of Cu2+ led to a naked-eye color and
      spectral changes according to the binding site-signaling subunit approach. Then,
      the RB4-Cu2+ complex was successfully applied for Cys and Arg through different
      recognition pathways. The optical signals for Arg were observed due to its
      association involving the amino group, as well as the participation of the
      carboxylate group in a bidentate form to the complex, while selective behavior
      for Cys was explained by a metal displacement mechanism. The limits of detection
      for Cu2+, Arg, and Cys were calculated to be 1.96, 1.06, and 1.33 MUmol L-1,
      respectively. It could also be employed for the determination of three analytes
      in environmental, biological, and pharmaceutical samples. Importantly, the test
      strips based on RB4-Cu2+ complex could be used as a solid-state sensor for the
      detection of Cys and Arg. In addition, NAND and IMPLICATION molecular logic gates
      were obtained by using chemical inputs and UV-Vis absorbance signal as the
      output. Graphical Abstract ?.

PMID- 30105546
TI  - The Role of Lignocellulosic Composition and Residual Lipids in Empty Fruit
      Bunches on the Production of Humic Acids in Submerged Fermentations.
AB  - The aim of this research was to study the production of humic acids (HA) by
      Trichoderma reesei from empty fruit bunches (EFBs) of palm oil processing, with a
      focus on the effects of lignocellulosic content and residual lipids. EFBs from
      two different soils and palm oil producers were previously characterized about
      their lignocellulosic composition. Submerged fermentations were inoculated with
      T. reesei spores and set up with or without residual lipids. The results showed
      that the soil and the processing for removal of the palm fresh fruits were
      crucial to EFB quality. Thus, EFBs were classified as type 1 (higher
      lignocellulosic and fatty acids composition similar to the palm oil and palm
      kernel oil) and type 2 (lower lignocellulosic content and fatty acids composition
      similar to palm oil). Despite the different profiles, the fungal growth was
      similar for both EFB types. HA production was associated with fungal growth, and
      it was higher without lipids for both EFBs. The highest HA productivity was
      obtained from type 1 EFB (approximately 90 mg L-1 at 48 h). Therefore, the
      lignocellulosic composition and the nature of the residual lipids in EFBs play an
      important role in HA production by submerged fermentation.

PMID- 30105547
TI  - Genetic basis of hypertrophic cardiomyopathy in children.
AB  - BACKGROUND: Previous investigations assessing the genetic cause of pediatric
      hypertrophic cardiomyopathy (HCM) found underlying genetic mutations in 50-60% of
      cases. The purpose of our study was to analyze whether this number can be
      augmented by applying next-generation sequencing and directing further
      diagnostics by discussing unsolved cases in a multidisciplinary board. METHODS
      AND RESULTS: 42 patients with the diagnoses of HCM made before age 18 years were
      treated in our center from 2000 to 2016. Genetic analysis was performed in 36
      subjects, a genetic defect was detected in 29 (78%) patients. 15 individuals
      (42%) had pathogenic variants in genes encoding sarcomere proteins, and 5 (14%)
      in genes coding for components of the RAS/MAPK signaling pathway. 4 subjects
      (11%) had mutations in the GAA gene (Pompe disease), and 3 (8%) had Frataxin
      repeat expansions (Friedreich's ataxia). One patient each showed a mutation in
      BAG3 and LMNA. Discussion of unsolved HCM cases after performing next-generation
      sequencing (28 genes) in an interdisciplinary board unraveled the genetic cause
      in 9 subjects (25%). CONCLUSION: A definite genetic diagnosis can be reached in
      nearly 80% with HCM of childhood onset. Next-generation sequencing in conjunction
      with a multidisciplinary cooperation can enhance the diagnostic yield
      substantially. This may be important for risk stratification, treatment planning
      and genetic counseling.

PMID- 30105548
TI  - ADAMTS5 acts as a tumor suppressor by inhibiting migration, invasion and
      angiogenesis in human gastric cancer.
AB  - BACKGROUND: ADAMTS5 has been reported to be involved in the progression of
      several human tumors. Nevertheless, the role of ADAMTS5 in gastric cancer (GC)
      remains poorly defined. METHODS: ADAMTS5 expression levels were analyzed by
      quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in GC cell
      lines and tissues, and the correlations between ADAMTS5 expression and
      clinicopathological features and survival were also examined. In vitro assays,
      including transwell assays, wound healing assays and cell adhesion assays, were
      employed to further explore the biological functions of ADAMTS5. A MAP kinase
      pathway microarray was used to identify the underlying mechanisms. The expression
      of ADAMTS5 and ETS1 and the microvessel density (MVD) were also analyzed using
      IHC to determine correlations with angiogenesis in GC. RESULTS: ADAMTS5
      expression was downregulated in gastric cancer tissues. Low expression of ADAMTS5
      was associated with gender, histological type, degree of differentiation, M
      stage, TNM stage and vascular invasion, and was also an independent indicator of
      a poor prognosis for patients with GC. ADAMTS5 overexpression markedly inhibited
      GC cell migration and invasion and enhanced cell adhesion to the extracellular
      matrix (ECM), whereas knockdown of ADAMTS5 exerted the opposite effects.
      Furthermore, the ADAMTS5 expression status was negatively correlated with ETS1
      expression and MVD. CONCLUSION: ADAMTS5 is downregulated in GC and suppresses
      tumor metastasis and angiogenesis by inhibiting ETS1-mediated changes in MVD and
      potentially acts as a novel prognostic marker and a potential therapeutic target
      in human GC.

PMID- 30105549
TI  - Potential for Cost Saving with Iclaprim Owing to Avoidance of Vancomycin
      Associated Acute Kidney Injury in Hospitalized Patients with Acute Bacterial Skin
      and Skin Structure Infections.
AB  - BACKGROUND AND OBJECTIVE: Vancomycin is the most prescribed antibiotic for
      hospitalized adults with skin and skin structure infections. Vancomycin is
      associated with acute kidney injury. Iclaprim is an antibiotic under development
      for the treatment of patients with acute bacterial skin and skin structure
      infections and is not associated with acute kidney injury. This economic model
      sought to determine the potential cost saving with iclaprim owing to avoidance of
      vancomycin-associated acute kidney injury among hospitalized patients with acute
      bacterial skin and skin structure infections. MATERIALS AND METHODS: A hospital
      cost-minimization model was developed to estimate the overall cost impact of
      replacing empiric vancomycin with iclaprim among hospitalized adult patients with
      skin and skin structure infections. The structural model included: vancomycin
      acquisition; vancomycin assay; incidence of vancomycin-associated acute kidney
      injury; excess hospital length of stay if acute kidney injury occurred;
      frequency/cost of specialty physician consults after occurrence of acute kidney
      injury; and probability/cost of acute dialysis as a result of acute kidney
      injury. Iclaprim treatment duration was 7 days and iclaprim acquisition cost was
      varied to determine the upper end of the daily iclaprim price that still
      conferred cost savings relative to vancomycin. Duration of hospitalization for
      iclaprim was assumed to be the same as patients with no acute kidney injury.
      RESULTS: Based on the overall acute kidney injury rate (9.2%), the neutral
      acquisition price threshold for iclaprim vs. vancomycin was US$1373.47/regimen.
      Across various subpopulations where acute kidney injury risk ranged between 9.2
      and 16.7%, the daily iclaprim acquisition cost that still conferred cost savings
      was up to US$300/day. CONCLUSIONS: Iclaprim has the potential to reduce the
      economic burden of acute bacterial skin and skin structure infections in
      hospitalized patients at risk for vancomycin-associated acute kidney injury when
      iclaprim acquisition is US$300/day or less.

PMID- 30105550
TI  - Cardioprotective role of FA against isoproterenol induced cardiac toxicity.
AB  - The present study was designed to investigate the protective effect of ferulic
      acid (FA) against isoproterenol (ISO)-induced cardiac toxicity in rats.
      Isoproterenol challenged in a dose of 85 mg/kg body weight (b.w.) subcutaneously
      for two consecutive days in the experimental group resulted in acute cardiac
      toxicity as evidenced by changes in electrocardiogram (ECG) pattern and marked
      elevation of serum cardiac enzymes viz aspartate aminotransferase (AST), alanine
      transaminase (ALT), creatinine kinase (CK-MB) and lactate dehydrogenase (LDH)
      also increases inflammatory cytokines. Moreover, acute toxicity effect was
      exhibited by disturbance in the antioxidant system as decrease in activities of
      superoxide dismutase (SOD) and glutathione (GSH) with the rise in activities of
      malondialdehyde (MDA) and nitric oxide (NO). Pre-treatment with FA at the
      increasing dose of (10, 20 and 40 mg/kg b.w.) orally for 28 consecutive days
      followed by isoproterenol injection for 2 days significantly attenuated changes
      in serum cardiac enzymes. Furthermore, histopathological evaluation confirmed the
      restoration of cellular architecture in FA pretreated rats. The cardioprotective
      effect of FA was comparable with standard drug treatment metoprolol. Taken
      together, FA demonstrated cardioprotective effect against ISO-induced cardiac
      toxicity by normalization of serum cardiac biomarkers, alleviating oxidative
      stress and augmenting endogenous antioxidant system.

PMID- 30105551
TI  - Transgenic creeping bentgrass plants expressing a Picea wilsonii dehydrin gene
      (PicW) demonstrate improved freezing tolerance.
AB  - Agrostis stolonifera L. 'Penn A-4' is a common creeping bentgrass species that is
      widely used in urban landscaping and golf courses. To prolong the green stage of
      this grass, a dehydrin gene PicW isolated from Wilson's spruce (Picea wilsonii)
      was transformed into plants of 'Penn A-4' cultivar via a straightforward stolon
      node infection system. A putative transgenic plant was obtained and its tolerance
      to low-temperature stress was evaluated. When the transgenic line was subjected
      to a freezing (- 5  degrees C) treatment, it showed better viability and more
      robust physiology than wild type, as evidenced by higher soluble sugar and
      proline contents, and lower relative electrical conductivity and malondialdehyde
      content. The transgenic line also showed tolerance to a chilling treatment (5 
      degrees C), although its performance was not significantly different from that of
      wild-type plants. Overall, the research here clearly revealed the explicit role
      of PicW in increasing freezing tolerance of grass at the whole-plant level, and
      demonstrated that the straightforward stolon node transformation method could be
      well used to genetically modify turfgrass. The obtained transgenic line might be
      as genetic resource for breeding program and practiced to grow in cold temperate
      zones.

PMID- 30105552
TI  - Genetic lesions in the UGT1A1 genes among Gilbert's syndrome patients from India.
AB  - The present study was undertaken to investigate genetic variations present in the
      coding regions of the UGT1A1 gene among the Gilbert's syndrome patients. Analysis
      of genetic variations was performed by direct DNA sequencing among the patients
      that do not have any polymorphic variations in the promoter regions of the UGT1A1
      gene. We identified seven different sequence variations among Gilbert's Syndrome
      patients, of which four were novel. Out of seven variants, six missense and one
      silent single nucleotide substitutions were present in the UGT1A1 gene. In
      addition, molecular modeling of UGT1A1 (H55R, P152S and N212H) variants suggested
      a reduced activity of the enzyme. This study demonstrates that different
      variations present in the UGT1A1 gene and specifically, the H55R variation had a
      significant effect on bilirubin levels and could be genetic risk factors for
      hyperbilirubinemia.

PMID- 30105553
TI  - Estimation in self-initiated working memory for spatial locations.
AB  - The short-term maintenance of precise location information is fundamental in many
      daily activities. Often, individuals memorize spatial information provided to
      them, but in many other occasions memory is self-initiated, meaning that
      individuals memorize locations they selected themselves. While prevalent in
      everyday behavior, research on self-initiated working memory (WM) is scarce. The
      current study employed a modified spatial precision memory task in which
      participants temporarily memorized single locations they themselves selected
      within a square area that appeared during encoding. We explored the distribution
      of locations participants selected, guided by the assumption that participants
      would select locations that they perceived would maximize accuracy. The results
      of two experiments demonstrated that, to enhance memory performance, participants
      most often selected prototypical locations within the square area, namely, at its
      center and at its corners, which were closest to the center and the corners of
      the entire screen. When asked to disrupt memory performance, participants mostly
      avoided these locations. Furthermore, memory accuracy for self-initiated
      locations was superior to memory for provided locations, even when the
      distribution of locations in the two conditions was matched. We interpret the
      results within the framework of models that emphasize the utility of spatial
      categories in maximizing memory accuracy in spatial-estimation tasks. The results
      provide the first illustration of self-initiated representations in spatial
      precision WM tasks, suggesting that participants have access to metacognitive
      knowledge about the usefulness of spatial categories in location memory.
      Moreover, the results demonstrate that spatial precision is enhanced when
      participants reproduce locations they selected themselves.

PMID- 30105554
TI  - ["De optima lithotomiam administrandi ratione" : A dissertation from 1713 about
      the various possibilities of the cystotomy by Johann Michael Eisenbarth, the son
      of the well-known travelling physician Johann Andreas Eisenbarth (1663-1727)].
AB  - The present dissertation was submitted in 1713 at the University of Halle as part
      of the requirements to obtain the "licentiat". The author was Johann Michael
      Eisenbarth, the oldest son of the well-known physician Johann Andreas Eisenbarth.
      The dissertation delivers an overview over the history of the cystotomy, leading
      back to antiquity. In sixty paragraphs, the author dealt with different issues,
      such as diagnosis, preparation, and aftercare of patients with urinary bladder
      stones. However, the center of the thesis is the critical evaluation of all
      surgical methods known three hundred years ago.

PMID- 30105556
TI  - Regioselective formation of 1,2,4-triazoles by the reaction of amidrazones in the
      presence of diethyl azodicarboxylate and catalyzed by triethylamine.
AB  - A general method for the synthesis of 1,3,5-trisubstituted 1,2,4-triazoles has
      been developed from reaction of amidrazones with ethyl azodicarboxylate and
      triethylamine (Mitsunobu reagent) in EtOH. This highly regioselective one-pot
      process provides rapid access to highly diverse triazoles. The reaction was
      explained, based on Mitsunobu reagent oxidizing ethanol to acetaldehyde, which
      would then react with amidrazones to give the substituted 3-methyltriazoles. A [2
      + 3] cycloaddition reaction between two oxidized forms of amidrazones produced
      the second type of triazoles. X-ray structure analyses proved the structure of
      each type of product.

PMID- 30105555
TI  - Genetics of Dilated Cardiomyopathy: Clinical Implications.
AB  - PURPOSE OF REVIEW: This review aims to summarize the current knowledge on the
      genetic background of dilated cardiomyopathy (DCM), with particular attention to
      the genotype-phenotype correlations and the possible implications for clinical
      management. RECENT FINDINGS: Next generation sequencing (NGS) has led to the
      identification of an increasing number of genes and mutations responsible for
      DCM. This genetic variability is probably related to the extreme heterogeneity of
      disease manifestation. Important findings have associated mutations of Lamin A/C
      (LMNA) and Filamin C (FLNC) to poor prognosis and the propensity to cause an
      arrhythmic phenotype, respectively. However, a deeper understanding of the
      genotype-phenotype correlation is necessary, because it could have several
      implications for the clinical management of the patients. Furthermore, the
      correct interpretation of pathogenicity of mutations and the clinical impact of
      genetic testing in DCM patients still represent important fields to be
      implemented. A pathogenic gene mutation can be identified in almost 40% of DCM
      patients. The recent discoveries and future research in the field of genotype
      phenotype correlation may lead to a more personalized management of the mutation
      carriers towards the application of precision medicine in DCM.

PMID- 30105557
TI  - Imaging Protocols for Active Surveillance in Renal Cell Carcinoma.
AB  - PURPOSE OF REVIEW: To review the growth kinetics of small renal masses and
      available imaging modalities for mass characterization and surveillance,
      highlight current organizational recommendations for the active surveillance of
      small renal masses, and discuss the most recently reported oncological outcomes
      of patients as they relate to various surveillance imaging protocols and
      progression to delayed intervention. RECENT FINDINGS: Overall, organizational
      guideline recommendations are broad and lack specifics regarding timing and
      modality for follow-up imaging of small renal masses. Additionally, despite
      general consensus in the literature about certain criteria to trigger delayed
      intervention, there exist no formal guidelines. Active surveillance of small
      renal masses is an acceptable management strategy for patients with prohibitive
      surgical risk; however, standardized imaging protocols for surveillance are
      lacking, as are randomized, prospective trials to evaluate the ideal follow-up
      protocol.

PMID- 30105559
TI  - [Acute diseases of the brain and heart : A reciprocal culprit-victim
      relationship].
AB  - The reciprocal culprit-victim relationship between the brain and the heart leads
      to dysfunction and damage to the other organ, especially in acute and severe
      diseases of one of both organs. In addition, both organ systems can be affected
      by identical systemic processes, e. g., arteriosclerotic changes. Cardiac embolic
      formation and pumping failure lead to focal cerebral ischemia or global hypoxia.
      Cerebral diseases leading to cardiac changes are acute cerebrovascular attacks
      such as cerebral infarction, intracerebral hemorrhage and subarachnoid
      hemorrhage, as well as epileptic seizures. The pathophysiological mechanisms of
      changes of the brain-heart axis include cerebrally induced autonomic
      dysregulation, neuroendocrine regulatory disorders, and systemic inflammatory
      processes. The effects on the heart are evident in up to 75% of patients with
      acute brain diseases leading to ECG changes, arrhythmias, increase in cardiac
      enzymes and myocardial damage even to sudden cardiac death. For this reason,
      cardiac monitoring should be provided in severe acute brain diseases.

PMID- 30105560
TI  - Flow-diverter Stents for Internal Carotid Artery Reconstruction Following
      Spontaneous Dissection: A Technical Report.
AB  - BACKGROUND AND PURPOSE: Extracranial internal carotid artery (ICA) dissection is
      an important cause of ischemic stroke in younger adults. The optimal medical and
      surgical strategies for managing these lesions have not been well established. We
      report a case series of extracranial ICA reconstruction using overlapping flow
      diverter stents as a rescue therapy for the treatment of symptomatic ICA
      dissection in patients presenting with recurrent ischemic stroke and/or severe
      hemispheric hypoperfusion who failed medical management. MATERIALS AND METHODS:
      Consecutive patients undergoing endovascular reconstruction of either occluded or
      severely narrowed ICA due to dissection and presenting with symptoms of recurrent
      cerebral ischemia or cerebral hypoperfusion were included. Data were collected on
      demographic characteristics, antiplatelet management, clinical presentation,
      imaging findings, treatment characteristics, complications and stroke recurrence
      rates. RESULTS: A total of 7 patients were included. The mean age was 47 years, 4
      patients were male and 3 were female. All patients were symptomatic presenting
      with ipsilateral recurrent ischemia with or without cerebral hemodynamic
      compromise and necessitated reconstructive treatment. Patients were placed on
      dual antiplatelet therapy with aspirin and either ticagrelor or clopidogrel prior
      to the procedure. In cases where patients were not preloaded with dual
      antiplatelets intravenous abciximab was used as a bridging therapy. Post-stenting
      angioplasty was performed if deemed necessary. There were no symptomatic ischemic
      or hemorrhagic complications. No patients had recurrent ischemic events.
      CONCLUSION: Reconstruction of the ICA as a rescue strategy for extracranial
      carotid dissection using flow-diverter stents is feasible and was performed
      without adverse events in this small series.

PMID- 30105561
TI  - Response to Letter to the Editor "Preoperative Digital Subtraction Angiography in
      Incidental Unruptured Intracranial Aneurysms".

PMID- 30105558
TI  - CXCR4-directed theranostics in oncology and inflammation.
AB  - Given its prominent role in inflammation and cancer biology, the C-X-C motif
      chemokine receptor 4 (CXCR4) has gained a lot of attention in the recent years.
      This review gives a short overview of the physiology and pathology of chemokines
      and chemokine receptors and then focuses on the current experience of targeting
      CXCR4, using radiolabeled receptor ligands suitable for positron emission
      tomography (PET) imaging, in both hematologic and solid malignancy as well as in
      inflammatory conditions. Additionally, CXCR4-directed endoradiotherapy (ERT) as a
      new treatment option is discussed.

PMID- 30105562
TI  - Prediction of Microdroplet Breakup Regime in Asymmetric T-Junction Microchannels.
AB  - Splitting droplets is becoming a major functional component in increasing number
      of droplet microfluidic applications, and there is an increasing interest in
      splitting droplets into two daughter droplets with different volumes. However,
      designing an asymmetric droplet splitter and predicting how a droplet splits in
      such designs is not trivial. In this study, numerical simulations were conducted
      to study droplet breakup in asymmetric T-junctions of square cross-sections
      having different pressure gradient ratios (i.e. T-junctions with outlet branches
      of different lengths). The goal of the simulation is to identify the conditions
      where a parent droplet breaks or does not break into two smaller droplets of
      different sizes (so called critical condition) and to identify the important
      fluid and microchannel parameters in this process. Four modes of droplet breakup
      (primary-, transition-, bubble-, and non-breakups) are identified and an
      empirical correlation is introduced that can predict the breakup/non-breakup of
      the droplet based on the parent droplet size and the capillary number. The
      simulation results are then compared with experimental data to verify its
      accuracy and the effect of fluids properties on the proposed correlation are
      studied. Two major asymmetric breakup mechanisms are determined, namely "breakup
      with permanent obstruction" and "unstable breakup". The numerical results show
      that the splitting ratio for the asymmetric breakup mechanisms depends on flow
      conditions and dwell time of the droplet at the junction prior to splitting.
      Finally, the results from two-dimensional and three-dimensional simulations were
      compared. It is shown that two-dimensional simulation may not accurately predict
      the breakup behavior for asymmetric droplet breakup and viscosity ration has a
      greater effect on the prediction critical condition.

PMID- 30105565
TI  - [Wie schreibe ich ein Paper].

PMID- 30105564
TI  - [Vitrectomy and iOCT-assisted inverted ILM flap technique in patients with full
      thickness macular holes].
AB  - BACKGROUND: In large full thickness macular holes (FTMH) the closure rate after
      vitrectomy and conventional internal limiting membrane (ILM) peeling is less than
      90%. The aim of this study was to examine the visual acuity and anatomical
      success rate with high-resolution optical coherence tomography (OCT) after
      transconjunctival sutureless 23-gauge pars plana vitrectomy as well as
      intraoperative OCT (iOCT) and Brilliant Peel (BP)-assisted ILM peeling using the
      inverted ILM flap technique in patients with large FTMHs. METHOD: In this
      retrospective study 25 eyes of 25 consecutive patients with large FTMH were
      treated by 23-G vitrectomy with BP and iOCT-assisted ILM peeling using the
      inverted ILM flap technique followed by gas tamponade. In all patients best
      corrected visual acuity (BCVA) and the maximum diameter, base and height of the
      FTMH as well as intraretinal alterations were measured preoperatively using high
      resolution spectral domain OCT (SD-OCT, Spectralis, Heidelberg Engineering,
      Germany). The BCVA was measured after 1, 3, and 6 months. Additionally, the
      closure rate and the microstructural integrity of the outer retinal layers, e.g.
      external limiting membrane (ELM), ellipsoid zone und photoreceptor outer segment
      (OS) were registered in the SD-OCT and correlated with the results of BCVA after
      macular hole surgery. RESULTS: In all surgical procedures with the inverted ILM
      flap technique the application of iOCT enabled a good visualization and a
      controlled positioning of the ILM flaps. At baseline mean BCVA was 0.2 (0.7
      logMAR) and improved significantly after 1, 3 und 6 months to 0.4 (0.4 logMAR),
      0.5 (0.3 logMAR) and 0.63 (0.2 logMAR), respectively. The closure rate of the
      FTMHs was 100%. Microstructural integrity of the outer retinal layers was
      evaluated semiquantitatively and showed good correlation with BCVA. CONCLUSION:
      Vitrectomy with BP and iOCT-assisted ILM peeling using the inverted ILM flap
      technique in patients with large FTMH is a very controlled and safe microsurgical
      strategy and shows good functional and anatomical results. The morphology of the
      FTMH, the ILM flap and the position of the inverted ILM flap under air was well
      visualized by IOCT. The microstructural integrity of the outer retinal layers is
      displayed in detail on SD-OCT and represents an important predictive parameter
      for BCVA after macular hole surgery.

PMID- 30105566
TI  - Torticollis After a Somersault: A Case of Grisel's Syndrome.

PMID- 30105563
TI  - Silent Orthohantavirus Circulation Among Humans and Small Mammals from Central
      Minas Gerais, Brazil.
AB  - New World orthohantaviruses are emerging RNA viruses that cause hantavirus
      cardiopulmonary syndrome (HCPS). These viruses are a burden to public health
      around the world with a lethality rate of around 60%. In South America, rodents
      of Sigmodontinae subfamily are the main reservoirs of orthohantaviruses. We
      described a serosurvey for orthohantaviruses circulation in an apparently healthy
      human population and small mammals from rural areas in Central Minas Gerais
      State, Brazil. A total of 240 individuals and 50 small mammals (26 rodents
      belonging to 10 different species and 24 marsupials from 4 different species)
      were sampled during 2012-2013. The seroprevalence rates of IgG/IgM antibodies in
      humans were 7.1 and 1.6%, respectively. Only one rodent, an Oligoryzomys nigripes
      captured in peridomestic area, tested positive for IgG antibodies and viral RNA.
      Our findings suggest a silent circulation of orthohantaviruses in a region of
      intensive agriculture production. The detection of seropositive humans in an area
      with a lack of previous HCPS reports highlights potential oligosymptomatic cases
      and the need for surveillance strategies that could reduce the risk of future
      outbreaks.

PMID- 30105567
TI  - Goiter Prevalence and Interrelated Components from Coastal Karnataka.
AB  - OBJECTIVE: To assess prevalence of goiter and associated factors among school
      going children in Udupi district. METHODS: A school based cross-sectional survey
      was conducted among 6-12 year old children. A sample of 30 villages was selected
      from the entire district by probability proportionate to size. One school was
      then randomly selected from each of the 30 villages. Goiter was assessed
      clinically and was graded as per the recommended criteria of World Health
      Organization (WHO)/ United Nations Children's Fund (UNICEF)/ International
      Council for the Control of Iodine Deficiency Disorders (ICCIDD). Salt and urine
      samples were collected from a subsample for iodine estimation. RESULTS: A total
      of 2703 children were examined. The mean (+/-SD) age of the participants was 9.6
      y (+/-1.9). The overall prevalence of goiter in Udupi district was found to be
      9.3% with 7.0% and 2.3% having grade 1 and grade 2 goiter respectively.
      Prevalence of goiter was significantly higher among females [153(11.1%)] as
      compared to males [98(7.4%)] (p = 0.001). Of the 543 salt samples analyzed, 379
      (69.8%) salt samples had adequate salt iodine content (> 15 ppm); while among the
      children with goiter 32 (8.4%) had inadequate salt iodine. Median iodine value
      was 202.12 mcg/l among the 270 urine samples tested for iodine levels.
      CONCLUSION: Goiter prevalence at 9.3% in the coastal district contributes to the
      endemicity of the public health problem. The district had adequate iodine
      nutrition based on median urinary iodine levels. Hence, other contributing
      factors for the persistence of endemic goiter need to be explored.

PMID- 30105568
TI  - Brain activation during repeated imagining of chocolate consumption: a functional
      magnetic resonance imaging study.
AB  - OBJECTIVE: To assess brain activation during mental visualization of eating
      chocolate. DESIGN: Twenty-one subjects were included. FMRI was acquired with a
      single-shot, multislice, gradient echo-planar sequence, while subjects were
      performing two specific imaginary tasks. RESULTS: Activation of motor-associated
      brain areas was observed during both mental visualization tasks. Increased
      activation of the right dorsolateral prefrontal cortex, the thalamus, the
      postcentral gyrus and the left anterior cingulate cortex, and the precuneus was
      observed during imagining eating chocolate. CONCLUSIONS: Repeated imagination of
      chocolate consumption results in activation of brain areas associated with
      hedonic effects of food and satiety and inhibition of orexigenic areas.

PMID- 30105569
TI  - Unfounded conclusions of equivalence in diagnostic accuracy studies: a pervasive
      fallacy of inference in pediatric radiology scientific abstracts.
AB  - BACKGROUND: In studies of diagnostic performance that fail to detect a
      statistically significant difference between compared techniques, investigators
      often declare evidence of equivalence or similarity without having actually
      tested that assertion due to incorrect methodology or insufficient statistical
      power. OBJECTIVE: The purpose of our investigation is to measure the prevalence
      of unfounded assertions of equivalence or similarity in comparison studies
      presented at the International Pediatric Radiology (IPR) meeting of 2016 and
      promote awareness of this fallacy of inference to the pediatric radiology
      community. MATERIALS AND METHODS: Two pediatric radiologists independently
      reviewed the methodology and reporting quality of the 194 scientific paper
      abstracts from the 2016 IPR meeting. All comparison studies were identified and
      those failing to detect a statistically significance difference and making a
      claim of equivalence or similarity in the results or conclusion were assessed for
      a description of the study design type, statistical power and sample size
      estimator calculation. RESULTS: Of 194 scientific paper abstracts, 112 (58%) were
      comparison studies. Of these, 36/112 (32%) made unfounded inferences of
      equivalence or similarity in diagnostic imaging performance. No study had an
      equivalence or non-inferiority design. No abstract specified the statistical
      power of the study, and only one abstract acknowledged a small sample size as a
      limitation in detecting a statistically significant difference. CONCLUSION:
      Inadequate reporting and unfounded inferences of equivalence or similarity were
      common in diagnostic performance comparison studies presented at IPR 2016.
      Failure to recognize these limitations could have adverse consequences by leading
      to the adoption of unvalidated imaging techniques.

PMID- 30105570
TI  - Azoreductase from alkaliphilic Bacillus sp. AO1 catalyzes indigo reduction.
AB  - Indigo is an insoluble blue dye historically used for dyeing textiles. A
      traditional approach for indigo dyeing involves microbial reduction of polygonum
      indigo to solubilize it under alkaline conditions; however, the mechanism by
      which microorganisms reduce indigo remains poorly understood. Here, we aimed to
      identify an enzyme that catalyzes indigo reduction; for this purpose, from
      alkaline liquor that performed microbial reduction of polygonum indigo, we
      isolated indigo carmine-reducing microorganisms. All isolates were facultative
      anaerobic and alkali-tolerant Bacillus spp. An isolate termed AO1 was found to be
      an alkaliphile that preferentially grows at pH 9.0-11.0 and at 30-35  degrees C.
      We focused on flavin-dependent azoreductase as a possible enzyme for indigo
      carmine reduction and identified its gene (azoA) in Bacillus sp. AO1 using
      homology-based strategies. azoA was monocistronic but clustered with ABC
      transporter genes. Primary sequence identities were < 50% between the azoA
      product (AzoA) and previously characterized flavin-dependent azoreductases. AzoA
      was heterologously produced as a flavoprotein tolerant to alkaline and organic
      solvents. The enzyme efficiently reduced indigo carmine in an NADH-dependent
      manner and showed strict specificity for electron acceptors. Notably, AzoA
      oxidized NADH in the presence, but not the absence, of indigo. The reaction rate
      was enhanced by adding organic solvents to solubilize indigo. Absorption spectrum
      analysis showed that indigo absorption decreased during the reaction. These
      observations suggest that AzoA can reduce indigo in vitro and potentially in
      Bacillus sp. AO1. This is the first study that identified an indigo reductase,
      providing a new insight into a traditional approach for indigo dyeing.

PMID- 30105572
TI  - Tegmento-vermian dysplasia: radiologic features of a novel described anatomic
      variation.
AB  - Here we present the incidental radiological findings of a case that has a huge
      pontine tegmental cap orienting posteriorly towards the fourth ventricle and
      continues with the inferior vermis, accompanied by a midline anterior midbrain
      cleft. Having knowledge about this variation will prevent a misdiagnosis of a
      posterior fossa tumor and eventual unnecessary biopsy or operation.

PMID- 30105571
TI  - Engineering Salinispora tropica for heterologous expression of natural product
      biosynthetic gene clusters.
AB  - The marine actinomycete genus Salinispora is a remarkably prolific source of
      structurally diverse and biologically active secondary metabolites. Herein, we
      select the model organism Salinispora tropica CNB-440 for development as a
      heterologous host for the expression of biosynthetic gene clusters (BGCs) to
      complement well-established Streptomyces host strains. In order to create an
      integratable host with a clean background of secondary metabolism, we replaced
      three genes (salA-C) essential for salinosporamide biosynthesis with a cassette
      containing the Streptomyces coelicolor PhiC31 phage attachment site attB to
      generate the mutant S. tropica CNB-4401 via double-crossover recombination. This
      mutagenesis not only knocks-in the attachment site attB in the genome of S.
      tropica CNB-440 but also abolishes production of the salinosporamides, thereby
      simplifying the strain's chemical background. We validated this new heterologous
      host with the successful integration and expression of the thiolactomycin BGC
      that we recently identified in several S. pacifica strains. When compared to the
      extensively engineered superhost S. coelicolor M1152, the production of
      thiolactomycins from S. tropica CNB-4401 was approximately 3-fold higher. To the
      best of our knowledge, this is the first example of using a marine actinomycete
      as a heterologous host for natural product BGC expression. The established
      heterologous host may provide a useful platform to accelerate the discovery of
      novel natural products and engineer biosynthetic pathways.

PMID- 30105573
TI  - Contemporary Management of the Newly Diagnosed Prostate Cancer Patient with
      Metastatic Disease at Presentation.
AB  - PURPOSE OF REVIEW: Androgen deprivation therapy (ADT) has been the standard-of
      care (SOC) for metastatic hormone-sensitive prostate cancer (mHSPC) since the
      middle of the twentieth century. Recently, several practice-changing trials have
      added new therapy options for these patients. Here we review these studies and
      discuss guidelines on treatment decision-making. RECENT FINDINGS: A trio of
      studies (GETUG-AFU15, STAMPEDE, CHAARTED) combining docetaxel chemotherapy with
      ADT all showed clinical benefit of the addition. More recently, the LATITUDE and
      STAMPEDE-Abiraterone studies established yet another new option for up-front
      treatment of newly diagnosed metastatic prostate cancer, showing significantly
      prolonged overall survival (OS) and progression-free survival (PFS) compared to
      ADT alone in men with high-risk mHSPC. With the recent demonstration that adding
      either docetaxel or abiraterone plus prednisone to ADT significantly improves
      survival in mHSPC, physicians are confronted by a growing body of clinical data
      and treatment regimens. Men with high-volume and/or high-risk metastatic disease
      should not be treated with ADT alone without strong consideration of docetaxel or
      abiraterone. The choice of a first-line therapy should be made based on risk
      stratification, patients' comorbidities, toxicities, quality-of-life (QOL)
      considerations, and cost.

PMID- 30105574
TI  - What Is Different About Applying to Medical School? (Positive) Implications for
      Academic Psychiatry.

PMID- 30105575
TI  - A Call to Action: the Need for Integration of Transgender Topics in Psychiatry
      Education.

PMID- 30105576
TI  - Training as a Psychiatrist When Having a Psychiatric Illness.

PMID- 30105578
TI  - Co-synthesis of kenyacin 404 and heterologous thurincin H enhances the
      antibacterial activity of Bacillus thuringiensis.
AB  - OBJECTIVES: To develop a recombinant strain of Bacillus thuringiensis that
      synthesizes two bacteriocins that enhance the antibacterial potency of the strain
      and that could have applied clinical and industrial value. RESULTS: We cloned the
      thurincin H cluster into the pHT3101 vector by assembling two genetic cassettes
      harboring genes for the synthesis, modification, immunity and transport of
      thurincin H. This construct was used to transform a thurincin H-sensitive strain
      of B. thuringiensis that synthesizes the kenyacin 404 to generate the recombinant
      Btk 404/pThurH which was immune to thurincin H and produces bacteriocins of
      approximately 3 kDa. A significant increase in the inhibitory activity,
      respectively, ~ 40 and 300%, was observed when compared with parental Btm 269 and
      Btk 404. Btk 404/pThurH showed increased activity against ten Gram-positive
      bacteria, including B. cereus, Listeria monocytogenes and B. pseudomycoides, and
      the Gram-negative bacterium, Sphingobacterium cabi. However, an antagonistic
      effect against Vibrio parahaemolyticus, relative to native strains, was observed.
      CONCLUSIONS: We have generated a recombinant strain of B. thuringiensis that co
      synthesizes two bacteriocins (kenyacin 404, thurincin H) with improved inhibitory
      activity, when compared with parental strains. To our knowledge, this is the
      first study that shows that B. thuringiensis could be manipulated to produce two
      bacteriocins, one being of heterologous origin, that enhance the antibacterial
      activity of the recombinant strain.

PMID- 30105577
TI  - Validation of the OncomineTM focus panel for next-generation sequencing of
      clinical tumour samples.
AB  - The clinical utility of next-generation sequencing (NGS) for a diverse range of
      targets is expanding, increasing the need for multiplexed analysis of both DNA
      and RNA. However, translation into daily use requires a rigorous and
      comprehensive validation strategy. The aim of this clinical validation was to
      assess the performance of the Ion Torrent Personal Genome Machine (IonPGMTM) and
      validate the OncomineTM Focus DNA and RNA Fusion panels for clinical application
      in solid tumour testing of formalin-fixed, paraffin-embedded (FFPE) tissue. Using
      a mixture of routine FFPE and reference material across a variety of tissue and
      specimen types, we sequenced 86 and 31 samples on the OncomineTM Focus DNA and
      RNA Fusion assays, respectively. This validation considered a number of
      parameters including the clinical robustness of the bioinformatics pipeline for
      variant detection and interpretation. The OncomineTM Focus DNA assay had a sample
      and variant-based sensitivity of 99.1 and 97.1%, respectively, and an assay
      specificity of 100%. The OncomineTM Focus Fusion panel had a good sensitivity and
      specificity based upon the samples assessed, however requires further validation
      to confirm findings due to limited sample numbers. We observed a good sequencing
      performance based upon amplicon, gene (hotspot variants within gene) and sample
      specific analysis with 92% of clinical samples obtaining an average amplicon
      coverage above 500X. Detection of some indels was challenging for the routine
      IonReporterTM workflow; however, the addition of NextGENe(r) software improved
      indel identification demonstrating the importance of both bench and bioinformatic
      validation. With an increasing number of clinically actionable targets requiring
      a variety of methodologies, NGS provides a cost-effective and time-saving
      methodology to assess multiple targets across different modalities. We suggest
      the use of multiple analysis software to ensure identification of clinically
      applicable variants.

PMID- 30105579
TI  - Importance of the preoperative cross-sectional area of the semispinalis cervicis
      as a risk factor for loss of lordosis after laminoplasty in patients with
      cervical spondylotic myelopathy.
AB  - PURPOSE: To investigate the effect of the preoperative cross-sectional area (CSA)
      of the semispinalis cervicis on postoperative loss of cervical lordosis (LCL)
      after laminoplasty. METHODS: A total of 144 patients who met the inclusion
      criteria between January 1999 and December 2015 were enrolled. Radiographic
      assessments were performed to evaluate the T1 slope, C2-7 sagittal vertical axis
      (SVA), cephalad vertebral level undergoing laminoplasty (CVLL), preoperative C2-7
      Cobb angle, and preoperative CSA of the semispinalis cervicis. RESULTS: The T1
      slope and the summation of the CSAs (SCSA) at each level of the semispinalis
      cervicis correlated with LCL, whereas the C2-7 SVA, CVLL, and preoperative C2-7
      Cobb angle did not. Multiple regression analysis demonstrated that a high T1
      slope and a low SCSA of the semispinalis cervicis were associated with LCL after
      laminoplasty in patients with cervical spondylotic myelopathy (CSM). The CSA of
      the semispinalis cervicis at the C6 level had the greatest association with LCL,
      which suddenly decreased with a LCL of 10 degrees . The best cutoff point of the
      CSA of the semispinalis cervicis at the C6 level, which predicts LCL > 10 degrees
      , was 154.5 mm2 (sensitivity 74.3%; specificity 71.6%; area under the curve
      0.828; 95% confidence interval 0.761-0.895). CONCLUSION: Preoperative SCSA of the
      semispinalis cervicis was a risk factor for LCL after laminoplasty. Spine
      surgeons should evaluate semispinalis cervicis muscularity at the C6 level when
      planning laminoplasty for patients with CSM. These slides can be retrieved under
      Electronic Supplementary Material.

PMID- 30105580
TI  - Novel pitcher plant-spider mutualism is dependent upon environmental resource
      abundance.
AB  - Positive species interactions are ubiquitous and crucial components of
      communities, but they are still not well incorporated into established ecological
      theories. The definitions of facilitation and mutualism overlap, and both are
      often context dependent. Many interactions that are facilitative under stressful
      conditions become competitive under more benign ones. This is known as the stress
      gradient hypothesis, which is a specific case of context dependency. Stress can
      be further divided into resource and non-resource categories, but a better
      mechanistic understanding is necessary to improve the theory's predictions. We
      examined if two pitcher-dwelling crab spiders (Thomisidae), Thomisus
      nepenthiphilus and Misumenops nepenthicola, can facilitate nitrogen sequestration
      in their pitcher plant host, Nepenthes gracilis, by ambushing pitcher-visiting
      flies and dropping their carcasses into pitchers after consumption. This
      relationship is, by definition, both mutualistic and facilitative. Laboratory
      experiments found that both crab spiders increased prey-capture rates of N.
      gracilis. Nutrient analyses showed that both crab spiders also decreased per unit
      nitrogen yield of prey. Using experiment duration as a proxy of prey-resource
      availability, we constructed a mechanistic conceptual model of nutritional
      benefit. The nutritional benefit received by N. gracilis from T. nepenthiphilus
      decreases with increasing levels of the limiting resource in the environment
      (i.e., decreasing levels of resource stress). Our findings suggest that any
      nutritional mutualism that increases the quantity of resource capture (e.g.
      number of prey individuals) but decreases the quality of the captured resource
      (e.g. nitrogen content of individual prey) will necessarily conform to the
      resource-based predictions of the stress gradient hypothesis.

PMID- 30105581
TI  - The interaction of temperature and precipitation determines productivity and
      diversity in a bunchgrass prairie ecosystem.
AB  - Over the past century at the National Bison Range, temperature has increased by
      0.6  degrees C, and annual precipitation has decreased by 26%, despite increases
      in May-June precipitation over the past 35 years. Limited experimental work to
      date has explored plant responses produced by the interaction of changes in both
      temperature and precipitation, and of the existing studies, none have focused on
      the endangered bunchgrass ecosystem. Using a 2-year climate change manipulation
      experiment, we show that bunchgrass productivity increased with supplemental
      growing season precipitation, while warming alone exerted no significant effect.
      More importantly, the ratio of June precipitation to minimum temperature, a
      representation of the interaction of climate variables, predicted bunchgrass
      productivity better than either climate variable individually. This ratio acted
      as a surrogate index reflecting increased evapotranspiration with rising
      temperatures and thus better predicting soil moisture available for plant growth.
      Experimental warming over the summer led to significantly lower plant species
      richness and biodiversity, while increased precipitation, when applied over the
      entire summer, counteracted some of these declines. Warming also led to greater
      and more rapid plant senescence over the summer, resulting in greater litter
      production [an increase of 47.82 +/- 17.82 (+/- SE) percentage points] and
      potential fire risk. Given the simultaneous changes in precipitation and
      temperature predicted for the next century, multi-factor experiments are
      essential to understand how ecosystems will respond to future climate scenarios.

PMID- 30105582
TI  - Anaerobic degradation of 2,4-dichlorophenoxyacetic acid by Thauera sp. DKT.
AB  - Thauera sp. strain DKT isolated from sediment utilized 2,4-dichlorophenoxyacetic
      acid (2,4D) and its relative compounds as sole carbon and energy sources under
      anaerobic conditions and used nitrate as an electron acceptor. The determination
      of 2,4D utilization at different concentrations showed that the utilization curve
      fitted well with the Edward model with the maximum degradation rate as 0.017 +/-
      0.002 mM/day. The supplementation of cosubstrates (glucose, acetate, sucrose,
      humate and succinate) increased the degradation rates of all tested chemical
      substrates in both liquid and sediment slurry media. Thauera sp. strain DKT
      transformed 2,4D to 2,4-dichlorophenol (2,4DCP) through reductive side-chain
      removal then dechlorinated 2,4DCP to 2-chlorophenol (2CP), 4-chlorophenol (4CP)
      and phenol before complete degradation. The relative degradation rates by the
      isolate in liquid media were: phenol > 2,4DCP > 2CP > 4CP > 2,4D ~ 3CP. DKT
      augmentation in sediment slurry enhanced the degradation rates of 2,4D and
      chlorophenols. The anaerobic degradation rates in the slurry were significantly
      slower compared to the rates in liquid media.

PMID- 30105584
TI  - Response to a letter to the editor by Mohammad Rasoul Ghadami et al.:
      "Obstructive sleep apnea in veterans with post-traumatic stress disorder: looking
      beyond their complaint".

PMID- 30105583
TI  - The Effect of Spray Cryotherapy on Microbial Biofilms in Chronic Rhinosinusitis.
AB  - PURPOSE OF REVIEW: Microbial biofilms seem to play an active role in the
      pathogenesis of chronic rhinosinusitis (CRS). They represent an adaptive defense
      resource enabling resistance to antibiotics and host defense mechanisms. Biofilms
      are thought to be accountable for refractory cases of sinusitis by perpetuating
      local inflammation. The objective of this study was to assess the effectiveness
      of spray cryotherapy as a biofilm disruption agent in CRS in an in vitro model.
      RECENT FINDINGS: A total of 23 patients with CRS undergoing endoscopic sinus
      surgery (ESS) were included. Rhinosinusal mucosa samples were harvested. Half of
      sample was left intact while the other half was treated with spray cryotherapy,
      so patients served as their own witnesses. Subsequently, they were processed to
      hematoxylin-eosin (HE) and toluidine blue (TB) staining and analyzed by light
      microscopy. Biofilms were detected in 17 of 23 patients with CRS. Staining by HE
      showed strong correlation with the results of TB staining protocol. The in vitro
      CRS study demonstrated that spray cryotherapy removed polymicrobial biofilms from
      the mucosa surface in 70.6% of cases and induced important structural changes in
      the remaining samples. Thus far, cryotherapy has proven to be a reliable method
      for the disruption of microbial biofilms in CRS with nasal polyps, in vitro
      conditions. Spray cryotherapy could be a considerable benefit in the management
      of recalcitrant CRS.

PMID- 30105585
TI  - Regulation of human brown adipose tissue by adenosine and A2A receptors - studies
      with [15O]H2O and [11C]TMSX PET/CT.
AB  - PURPOSE: Brown adipose tissue (BAT) has emerged as a potential target to combat
      obesity and diabetes, but novel strategies to activate BAT are needed. Adenosine
      and A2A receptor (A2AR) agonism activate BAT in rodents, and endogenous adenosine
      is released locally in BAT as a by-product of noradrenaline, but physiological
      data from humans is lacking. The purpose of this pilot study was to investigate
      the effects of exogenous adenosine on human BAT perfusion, and to determine the
      density of A2ARs in human BAT in vivo for the first time, using PET/CT imaging.
      METHODS: Healthy, lean men (n = 10) participated in PET/CT imaging with two
      radioligands. Perfusion of BAT, white adipose tissue (WAT) and muscle was
      quantified with [15O]H2O at baseline, during cold exposure and during intravenous
      administration of adenosine. A2AR density of the tissues was quantified with
      [11C]TMSX at baseline and during cold exposure. RESULTS: Adenosine increased the
      perfusion of BAT even more than cold exposure (baseline 8.3 +/- 4.5, cold 19.6 +/
      9.3, adenosine 28.6 +/- 7.9 ml/100 g/min, p < 0.01). Distribution volume of
      [11C]TMSX in BAT was significantly lower during cold exposure compared to
      baseline. In cold, low [11C]TMSX binding coincided with high concentrations of
      noradrenaline. CONCLUSIONS: Adenosine administration caused a maximal perfusion
      effect in human supraclavicular BAT, indicating increased oxidative metabolism.
      Cold exposure increased noradrenaline concentrations and decreased the density of
      A2AR available for radioligand binding in BAT, suggesting augmented release of
      endogenous adenosine. Our results show that adenosine and A2AR are relevant for
      activation of human BAT, and A2AR provides a future target for enhancing BAT
      metabolism.

PMID- 30105588
TI  - How Do Gay Serodiscordant Couples in Sydney, Australia Negotiate Undetectable
      Viral Load for HIV Prevention?
AB  - Many gay Australian serodiscordant couples are currently relying on an HIV
      positive partner's undetectable viral load (UVL) to practice condomless sex. For
      these couples, preventing HIV is often considered a mutual responsibility, yet
      they lack a formally endorsed strategy that helps them navigate 'UVL for
      prevention' (UfP) as a couple. Drawing on interviews with 21 Australian gay men
      representing 15 serodiscordant couples, we explored 'the couple' within
      serodiscordant HIV prevention. In learning to rely on UfP, couples were initially
      apprehensive as they navigated unfamiliar territory, but their concerns faded
      over time. Confidence in UfP was facilitated by repeated condomless sex without
      transmission, consistent test results, and being in a couple framed by trust,
      commitment, and familiarity. Gay male serodiscordant couples should be encouraged
      to negotiate clear, spoken 'viral load agreements' (VLAs) if they choose to rely
      on UfP.

PMID- 30105586
TI  - Oligomerization of a Bimolecular Ribozyme Modestly Rescues its Structural Defects
      that Disturb Interdomain Assembly to Form the Catalytic Site.
AB  - The emergence of cellular compartmentalization was a crucial step in the
      hypothetical RNA world and its evolution because it would not only prevent the
      extinction of RNA self-replication systems due to dispersion/diffusion of their
      components but also facilitate ribozyme reactions by molecular crowding effects.
      Here, we proposed and examined self-assembly of RNA components as a primitive
      cellular-like environment, which may have the ability to mimic cellular
      compartmentalization and crowding effects. We engineered a bimolecular group I
      ribozyme to form a one-dimensional (1D)-ribozyme assembly. In the 1D assembly
      form, severe mutations that inactivated the parent bimolecular ribozyme were
      modestly rescued resulting in weak catalytic ability.

PMID- 30105589
TI  - Erratum to: BURDEN 2020-Burden of disease in Germany at the national and regional
      level.
AB  - Erratum to:Bundesgesundheitsbl (2018) https://doi.org/10.1007/s00103-018-2793-0
      The original publication of this article contained an error in the list of the
      authors, in which the contributing author Christian Schmidt was missing. The full
      list of authors has now been updated. The original article ....

PMID- 30105590
TI  - MiR-1246 is upregulated and regulates lung cell apoptosis during heat stress in
      feedlot cattle.
AB  - Globally, heat stress seriously threatens productivity of cattle. The objective
      of this study was to identify novel miRNAs that regulated heat stress in feedlot
      cattle. Experiment was conducted under heat stress and normal conditions. With
      profiling miRNAs of each feedlot cattle, our results showed the level of miR-1246
      was significantly increased in these heat-stressed cattle (P < 0.05).
      Furthermore, by using bioinformatics analysis and luciferase reporter assays
      combined with qPCR and western blot, we found miR-1246 negatively regulated poly
      (C) binding protein 2 (PCBP2) and cAMP response element binding protein-like 2
      (CREBL2) mRNA and protein levels through binding to the 3'-UTR region (P < 0.05);
      further, it inhibited heat-induced apoptosis in lung cells. Finally, our results
      suggested that miR-1246 plays an important role in heat stress and it has the
      potential to be a novel modulation factor for heat stress in feedlot cattle.

PMID- 30105592
TI  - Sprengel's deformity of the shoulder joint treated by Woodward operation.
AB  - BACKGROUND: Sprengel's shoulder deformity is a rare condition that happens
      because of the abnormal termination of the caudal migration of the scapula during
      the embryonic period. METHODS: This retrospective clinical study included 10
      consecutive children who underwent a Woodward operation to correct the Sprengel's
      shoulder deformity. RESULTS: The average preoperative Cavendish grade for
      cosmetic evaluation was 3.5 (range 3-4), which decreased to 1.4 (range 1-2) at
      the final review (statistically significant, p > 0.002, Wilcoxon signed-rank
      test). Cavendish grade improvement and increase in abduction had a strong
      positive association (r = 0.681, Spearman correlation coefficient. CONCLUSION:
      The results showed that both functional and cosmetic outcome had a positive
      correlation with Woodward procedure. More cosmetic and functional improvement was
      seen at the last follow-up visit especially in cases where the operation was done
      in the younger years. LEVEL OF EVIDENCE: IV.

PMID- 30105591
TI  - Molecular cloning and characterization of calmodulin-like protein CaLP from the
      Scleractinian coral Galaxea astreata.
AB  - Optimal temperature and light are both necessary conditions for coral survival.
      Light enhances calcification, and thermal stress disrupts Ca2+ homeostasis. As
      calcium is involved in many important metabolic activities, in this study, we
      cloned the calmodulin-like protein (CaLP) gene of one of the scleractinian
      corals, Galaxea astreata. We also detected the relative mRNA expression levels of
      gaCaLP using the calcium channel blocker verapamil and CaCl2 treatment under
      conditions of light and dark, and compared expression levels under controlled
      temperature conditions. Full-length gaCaLP cDNA comprised 1290 nucleotides and
      contained 498 bp open reading frame that encoded a protein with 165 amino acids.
      With CaCl2, expression levels of gaCaLP only increased in the presence of light,
      suggesting that light may be a restrictive factor in CaLP expression when
      sufficient calcium is available in the environment. In addition, after verapami
      treatment, we noted that a down regulation of gaCaLP, suggesting that the
      expression of CaLP is closely related to extracellular Ca2+ influx. Under
      temperature stress at both high (30  degrees C) and low (20  degrees C)
      temperatures, expression levels of gaCaLP showed an initial increase, followed by
      a decreasing trend as treatment progressed. Expression levels reached their
      maximum value at 24 h. This result showed that CaLP participated in a temperature
      stress response, and Ca2+ homeostasis was disrupted during stress. The findings
      of the present study will help determine the function and regulatory mechanisms
      of gaCaLP.

PMID- 30105593
TI  - Safety and side-effect profile of intrathecal morphine in a diverse patient
      population undergoing total knee and hip arthroplasty.
AB  - Intrathecal morphine (ITM) can be useful for postoperative analgesia following
      lower extremity joint arthroplasty, but concerns exist regarding potential dose
      related side effects. In this study, we examined the safety and efficacy of ITM
      in patients undergoing lower extremity joint arthroplasty. We hypothesized that
      there would be (1) direct relationship between dosing and side effects, and (2)
      an inverse relationship between ITM dosing and 24-hour postoperative opioid
      requirement.

PMID- 30105594
TI  - Inferior acute myocardial infarction with anterior ST-segment elevations.

PMID- 30105596
TI  - Closed FacebookTM groups and CME credit: a new format for continuing medical
      education.
AB  - BACKGROUND: The International Hernia Collaboration (IHC) is a closed FacebookTM
      group that allows international surgeons to post clinical questions and exchange
      transparent feedback with the intent to optimize patient outcomes. Despite the
      educational value of closed FB groups, CME credits have not been available to
      members. To determine feasibility of and user interest in earning CME credit
      through social media, the IHC piloted a series of expert lectures followed by an
      interactive Facebook Live session as a novel pathway offering CME credit.
      METHODS: Nine monthly lectures and Facebook Live sessions were presented. CME
      credit was offered for the final seven lectures. Participation in the form of
      views, comments, and likes was quantified by a Facebook analytics service and an
      engagement score, defined as [(the number of comments * 2) + (the number of
      reactions)], was calculated for each lecture and Facebook Live session. CME
      credit was obtained through a two-question quiz. RESULTS: Of 5400 + Facebook
      members of the IHC, an average of 1116 (20.4 +/- 4.0%) viewed the live session
      event following each lecture (n = 9 events). The average Facebook engagement
      score for Facebook Live was 259 +/- 75, a significant difference with the average
      Facebook engagement score on the IHC (40.8) over the same time period (p <
      0.001). On average, 16 users [range 8-35, (n = 7 events)] claimed CME credit for
      each educational series. CONCLUSIONS: Closed Facebook groups can be a useful
      media to offer educational content and CME credit. The pilot IHC Lecture and
      Facebook Live series offering CME credit resulted in significantly more
      engagement amongst its members compared to other posts during the same time
      period. A small portion of participants qualified for CME credit. Future social
      media educational series may increase participants qualifying for CME by
      streamlining the interface to obtain CME credit.

PMID- 30105595
TI  - SLC2A9 (GLUT9) mediates urate reabsorption in the mouse kidney.
AB  - Uric acid (UA) is a metabolite of purine degradation and is involved in gout
      flairs and kidney stones formation. GLUT9 (SLC2A9) was previously shown to be a
      urate transporter in vitro. In vivo, humans carrying GLUT9 loss-of-function
      mutations have familial renal hypouricemia type 2, a condition characterized by
      hypouricemia, UA renal wasting associated with kidney stones, and an increased
      propensity to acute renal failure during strenuous exercise. Mice carrying a
      deletion of GLUT9 in the whole body are hyperuricemic and display a severe
      nephropathy due to intratubular uric acid precipitation. However, the precise
      role of GLUT9 in the kidney remains poorly characterized. We developed a mouse
      model in which GLUT9 was deleted specifically along the whole nephron in a
      tetracycline-inducible manner (subsequently called kidney-inducible KO or kiKO).
      The urate/creatinine ratio was increased as early as 4 days after induction of
      the KO and no GLUT9 protein was visible on kidney extracts. kiKO mice are
      morphologically identical to their wild-type littermates and had no spontaneous
      kidney stones. Twenty-four-hour urine collection revealed a major increase of
      urate urinary excretion rate and of the fractional excretion of urate, with no
      difference in urate concentration in the plasma. Polyuria was observed, but kiKO
      mice were still able to concentrate urine after water restriction. KiKO mice
      displayed lower blood pressure accompanied by an increased heart rate. Overall,
      these results indicate that GLUT9 is a crucial player in renal handling of urate
      in vivo and a putative target for uricosuric drugs.

PMID- 30105598
TI  - No evidence of Trichinella spp. in domestic pig carcasses at a selected abattoir
      in southern Botswana.
AB  - Trichinellosis is a worldwide zoonosis with genotypes affecting different
      domestic and wild animals and is widely distributed throughout the world. Species
      and genotypes of this genus affecting different animals have been identified.
      Despite its occurrence in Sub-Saharan countries, the presence of trichinellosis
      in Botswana is yet to be confirmed. The objective of this study was to determine
      the prevalence of Trichinella infection in domestic pigs slaughtered at an
      abattoir in Gaborone, Botswana. Of the 111 pig carcasses selected, 5 g of crus of
      the diaphragm was collected from each carcass, trimmed of all fat and fascia and
      then cut into 1- to 2-g samples. The muscle samples were pooled into 100-g muscle
      sample and then processed by the OIE prescribed digestion method. A
      stereomicroscope was used to examine each grid of the Petri dish for the presence
      of Trichinella larvae. No Trichinella larvae were found in any digested muscle
      samples. Future studies should target a wider pig population and other host
      animals.

PMID- 30105597
TI  - Obstetric Anti-phospholipid Syndrome: State of the Art.
AB  - PURPOSE OF REVIEW: This review focuses on new pathogenesis and clinical
      therapeutic aspects of obstetric anti-phospholipid syndrome (ob-APS) in the last
      5 years. RECENT FINDINGS: The pathogenesis of ob-APS is multifactorial, including
      placental infarctions, infiltration of inflammatory cells that cause acute and
      chronic inflammation, leading to uncontrolled inflammation and poor pregnancy
      outcomes. A preconception counseling and a patient-tailored treatment are
      fundamental to improve maternal and fetal outcomes. Thanks to conventional
      treatment, based on low-dose aspirin and heparin, 70% of women with ob-APS can
      have successful pregnancies. Women with positive anti-phospholipid antibodies
      (aPL) without clinical manifestations ("aPL carriers") or with obstetric
      manifestation not fulfilling ob-APS criteria need to be further investigated in
      order to assess their best management. Great interest has been given to drugs
      that could interact in the pathophysiological mechanisms, such as
      hydroxychloroquine, statins, and eculizumab. These drugs could be considered for
      patients refractory to conventional therapy.

PMID- 30105601
TI  - Mesenchymal Stem Cells and Calcium Phosphate Bioceramics: Implications in
      Periodontal Bone Regeneration.
AB  - In orthopedic medicine, a feasible reconstruction of bone structures remains one
      of the main challenges both for healthcare and for improvement of patients'
      quality of life. There is a growing interest in mesenchymal stem cells (MSCs)
      medical application, due to their multilineage differentiation potential, and
      tissue engineering integration to improve bone repair and regeneration. In this
      review we will describe the main characteristics of MSCs, such as osteogenesis,
      immunomodulation and antibacterial properties, key parameters to consider during
      bone repair strategies. Moreover, we describe the properties of calcium phosphate
      (CaP) bioceramics, which demonstrate to be useful tools in combination with MSCs,
      due to their biocompatibility, osseointegration and osteoconduction for bone
      repair and regeneration. Also, we overview the main characteristics of dental
      cavity MSCs, which are promising candidates, in combination with CaP bioceramics,
      for bone regeneration and tissue engineering. The understanding of MSCs biology
      and their interaction with CaP bioceramics and other biomaterials is critical for
      orthopedic surgical bone replacement, reconstruction and regeneration, which is
      an integrative and dynamic medical, scientific and bioengineering field of
      research and biotechnology.

PMID- 30105600
TI  - Association of frailty with short-term outcomes, organ support and resource use
      in critically ill patients.
AB  - PURPOSE: Frail patients are known to experience poor outcomes. Nevertheless, we
      know less about how frailty manifests itself in patients' physiology during
      critical illness and how it affects resource use in intensive care units (ICU).
      We aimed to assess the association of frailty with short-term outcomes and organ
      support used by critically ill patients. METHODS: Retrospective analysis of
      prospective collected data from 93 ICUs in Brazil from 2014 to 2015. We assessed
      frailty using the modified frailty index (MFI). The primary outcome was in
      hospital mortality. Secondary outcomes were discharge home without need for
      nursing care, ICU and hospital length of stay (LOS), and utilization of ICU organ
      support and transfusion. We used mixed logistic regression and competing risk
      models accounting for relevant confounders in outcome analyses. RESULTS: The
      analysis consisted of 129,680 eligible patients. There were 40,779 (31.4%) non
      frail (MFI = 0), 64,407 (49.7%) pre-frail (MFI = 1-2) and 24,494 (18.9%) frail
      (MFI >= 3) patients. After adjusted analysis, frailty was associated with higher
      in-hospital mortality (OR 2.42, 95% CI 1.89-3.08), particularly in patients
      admitted with lower SOFA scores. Frail patients were less likely to be discharged
      home (OR 0.36, 95% CI 0.54-0.79) and had higher hospital and ICU LOS than non
      frail patients. Use of all forms of organ support (mechanical ventilation, non
      invasive ventilation, vasopressors, dialysis and transfusions) were more common
      in frail patients and increased as MFI increased. CONCLUSIONS: Frailty, as
      assessed by MFI, was associated with several patient-centered endpoints including
      not only survival, but also ICU LOS and organ support.

PMID- 30105599
TI  - Association of conflicts of interest with the results and conclusions of goal
      directed hemodynamic therapy research: a systematic review with meta-analysis.
AB  - PURPOSE: The association between conflicts of interest (COI) and study results or
      article conclusions in goal-directed hemodynamic therapy (GDHT) research is
      unknown. METHODS: Randomized controlled trials comparing GDHT with usual care
      were identified. COI were classified as industry sponsorship, author conflict,
      device loaner, none, or not reported. The association between COI and study
      results (complications and mortality) was assessed using both stratified meta
      analysis and mixed effects meta-regression. The association between COI and an
      article's conclusion (graded as GDHT-favorable, neutral, or unfavorable) was
      investigated using logistic regression. RESULTS: Of the 82 eligible articles, 43
      (53%) had self-reported COI, and 50 (61%) favored GDHT. GDHT significantly
      reduced complications on the basis of the meta-analysis of studies with any type
      of COI, studies declaring no COI, industry-sponsored studies, and studies with
      author conflict but not on studies with a device loaner. However, no significant
      relationship between COI and the relative risk (GDHT vs. usual care) of
      developing complications was found on the basis of meta-regression (p = 0.25). No
      significant effect of GDHT was found on mortality. COI had a significant overall
      effect (p = 0.016) on the odds of having a GDHT-favorable vs. neutral conclusion
      based on 81 studies. Eighty-four percent of the industry-sponsored studies had a
      GDHT-favorable conclusion, while only 27% of the studies with a device loaner had
      the same conclusion grade. CONCLUSIONS: The available evidence does not suggest a
      close relationship between COI and study results in GDHT research. However, a
      potential association may exist between COI and an article's conclusion in GDHT
      research.

PMID- 30105603
TI  - "I Wasn't in My Right Mind": Qualitative Findings on the Impact of Alcohol on
      Condom Use in Patients Living with HIV/AIDS in Brazil, Thailand, and Zambia (HPTN
      063).
AB  - PURPOSE: There have been significant biomedical improvements in the treatment and
      prevention of HIV over the past few decades. However, new transmissions continue
      to occur. Alcohol use is a known barrier to medication adherence and consistent
      condom use and therefore may affect treatment as prevention (TasP) efforts. The
      purpose of this study was to further explore how alcohol is associated with
      condom use and sexual transmission behavior in three international cities.
      METHOD: HIV Prevention Trials Network 063 was an observational mixed-methods
      study of HIV-infected patients currently in care in Rio de Janeiro, Brazil;
      Chiang Mai, Thailand; and Lusaka, Zambia. Across these three global cities, 80
      qualitative interviews were conducted from 2010 to 2012. From these interviews,
      quotes related to substance use, almost all of which were alcohol, were analyzed
      using thematic analysis to identify how the use was related to sexual
      transmission behaviors. RESULTS: Overall, the theme that alcohol impairs
      cognitive abilities emerged from the data and included the following subthemes:
      expectancies, impaired decision-making, loss of control, and less concern for
      others. Themes specific to international settings and risk subgroups were also
      identified. CONCLUSION: Our analysis identified how alcohol influences sexual
      transmission behavior in HIV patients in three international settings. These
      findings may provide direction for content development for future secondary
      prevention interventions to effectively implement TasP internationally.

PMID- 30105602
TI  - Social Relationship Factors, Preoperative Depression, and Hospital Length of Stay
      in Surgical Patients.
AB  - PURPOSE: The interrelated associations of social relationship factors,
      depression, and outcomes of surgical patients are yet unexplored. The purpose of
      this study was to investigate whether depression mediates effects of general
      social support, loneliness, and living alone on hospital length of stay (LOS) of
      2487 patients from diverse surgical fields. METHOD: Social relationship factors
      and depression were assessed prior to surgery. The PROCESS macro for SPSS was
      used to conduct three simple mediation models that tested the indirect effects of
      social relationship factors on LOS mediated through depression. The models were
      adjusted for age, gender, preoperative physical health, surgical field, severity
      of medical comorbidity, and extent of surgical procedure. RESULTS: Social support
      and loneliness had significant indirect effects on LOS that were statistically
      mediated by preoperative depression. Lower social support and the feeling of
      loneliness were considerably related to higher depression which predicted longer
      LOS. While social support and loneliness had no direct effects on LOS, there was
      a small significant direct association of living alone with shorter LOS.
      CONCLUSION: Data suggest that social support and loneliness are indirectly
      related with surgical outcomes by an association with depression which in turn is
      related to worse outcomes. TRIAL REGISTRATION: NCT01357694.

PMID- 30105604
TI  - Annotation and detection of drug effects in text for pharmacovigilance.
AB  - Pharmacovigilance (PV) databases record the benefits and risks of different
      drugs, as a means to ensure their safe and effective use. Creating and
      maintaining such resources can be complex, since a particular medication may have
      divergent effects in different individuals, due to specific patient
      characteristics and/or interactions with other drugs being administered. Textual
      information from various sources can provide important evidence to curators of PV
      databases about the usage and effects of drug targets in different medical
      subjects. However, the efficient identification of relevant evidence can be
      challenging, due to the increasing volume of textual data. Text mining (TM)
      techniques can support curators by automatically detecting complex information,
      such as interactions between drugs, diseases and adverse effects. This semantic
      information supports the quick identification of documents containing information
      of interest (e.g., the different types of patients in which a given adverse drug
      reaction has been observed to occur). TM tools are typically adapted to different
      domains by applying machine learning methods to corpora that are manually
      labelled by domain experts using annotation guidelines to ensure consistency. We
      present a semantically annotated corpus of 597 MEDLINE abstracts, PHAEDRA,
      encoding rich information on drug effects and their interactions, whose quality
      is assured through the use of detailed annotation guidelines and the
      demonstration of high levels of inter-annotator agreement (e.g., 92.6% F-Score
      for identifying named entities and 78.4% F-Score for identifying complex events,
      when relaxed matching criteria are applied). To our knowledge, the corpus is
      unique in the domain of PV, according to the level of detail of its annotations.
      To illustrate the utility of the corpus, we have trained TM tools based on its
      rich labels to recognise drug effects in text automatically. The corpus and
      annotation guidelines are available at: http://www.nactem.ac.uk/PHAEDRA/ .

PMID- 30105605
TI  - Development of a Novel Human Cell-Derived Tissue-Engineered Heart Valve for
      Transcatheter Aortic Valve Replacement: an In Vitro and In Vivo Feasibility
      Study.
AB  - Transcatheter aortic valve replacement (TAVR) is being extended to younger
      patients. However, TAVR-compatible bioprostheses are based on xenogeneic
      materials with limited durability. Off-the-shelf tissue-engineered heart valves
      (TEHVs) with remodeling capacity may overcome the shortcomings of current TAVR
      devices. Here, we develop for the first time a TEHV for TAVR, based on human cell
      derived extracellular matrix and integrated into a state-of-the-art stent for
      TAVR. The TEHVs, characterized by a dense acellular collagenous matrix,
      demonstrated in vitro functionality under aortic pressure conditions (n = 4).
      Next, transapical TAVR feasibility and in vivo TEHV functionality were assessed
      in acute studies (n = 5) in sheep. The valves successfully coped with the aortic
      environment, showing normal leaflet motion, free coronary flow, and absence of
      stenosis or paravalvular leak. At explantation, TEHVs presented full structural
      integrity and initial cell infiltration. Its long-term performance proven, such
      TEHV could fulfill the need for next-generation lifelong TAVR prostheses.

PMID- 30105606
TI  - A case of concurrent diurnal and nocturnal paroxysmal dystonia.

PMID- 30105607
TI  - Video laryngoscopy versus direct laryngoscopy for first-attempt tracheal
      intubation in the general ward.
AB  - BACKGROUND: Recent trials showed that video laryngoscopy (VL) did not yield
      higher first-attempt tracheal intubation success rate than direct laryngoscopy
      (DL) and was associated with higher rates of complications. Tracheal intubation
      can be more challenging in the general ward than in the intensive care unit. This
      study aimed to investigate which laryngoscopy mode is associated with higher
      first-attempt intubation success in a general ward. METHODS: This is a
      retrospective study of tracheal intubations conducted at a tertiary academic
      hospital. This analysis included all intubations performed by the medical
      emergency team in the general ward during a 48-month period. RESULTS: For the 958
      included patients, the initial laryngoscopy mode was video laryngoscopy in 493
      (52%) and direct laryngoscopy in 465 patients (48%). The overall first-attempt
      success rate was 69% (664 patients). The first-attempt success rate was higher
      with VL (79%; 391/493) than with DL (59%; 273/465, p < 0.001). The first-attempt
      intubation success rate was higher among experienced operators (83%; 266/319)
      than among inexperienced operators (62%; 398/639, p < 0.001). In multivariate
      logistic regression analyses, VL, pre-intubation heart rate, pre-intubation SpO2
      > 80%, a non-predicted difficult airway, experienced operator, and Cormack-Lehane
      grade were associated with first-attempt intubation success in the general ward.
      Over all intubation-related complications were not different between two groups
      (27% for VL vs. 25% for DL). However, incidence of a post-intubation SpO2 < 80%
      was higher with VL than with DL (4% vs. 1%, p = 0.005), and in-hospital mortality
      was also higher (53.8% vs. 43%, p = 0.001). CONCLUSION: In a general ward
      setting, the first-attempt intubation success rate was higher with video
      laryngoscopy than with direct laryngoscopy. However, video laryngoscopy did not
      reduce intubation-related complications. Furthers trials on best way to perform
      intubation in the emergency settings are required.

PMID- 30105608
TI  - [Noninvasive mapping for catheter ablation of arrhythmias using the
      CardioInsightTM ECG vest].
AB  - BACKGROUND: CardioInsightTM is a noninvasive three-dimensional mapping system
      technology which offers a unique method for arrhythmia characterization and
      localization. With a 252-lead ECG vest on the patient's torso and a noncontrast
      CT scan, epicardial potentials are detected and by means of reconstruction
      algorithms activation and phase maps are created, offering a deeper understanding
      of localization and mechanisms of arrhythmias including atrial fibrillation
      without the need for an endocardial catheter. MATERIALS AND METHODS: The system
      has proven to be accurate and applicable in the clinical setting of accessory
      pathways, premature ventricular contractions (PVC), atrial tachycardias and
      atrial fibrillation. Beat-to-beat analysis offers detection and thus a
      therapeutic approach for arrhythmias which occur only paroxysmally such as
      supraventricular extrasystoles, atrial bursts or PVCs. Another advantage is the
      simultaneous display of various heart chambers such as the left and right atrium.
      However, major multicenter prospective randomized data are still lacking.
      CONCLUSION: If in the future noninvasive mapping could be achieved with MRI and
      if the technology was compatible with invasive mapping systems so that catheter
      positioning and noninvasive maps can be merged, the authors believe that this
      would represent a new dimension of mapping technology and ablation strategy of
      arrhythmias.

PMID- 30105610
TI  - [Erratum to: Requirements for a cross-location biobank IT infrastructure : Survey
      of stakeholder input on the establishment of a biobank network of the German
      Biobank Alliance (GBA)].

PMID- 30105609
TI  - [Ectopic tissue of the thyroid gland and the parathyroid glands].
AB  - Ectopic thyroid tissue results from developmental defects of the early stages of
      thyroid embryogenesis, in which the median thyroid anlage descends from the floor
      of the mouth to its final pre-tracheal position. The most common sites of ectopic
      thyroid tissue are accordingly in the area of the floor of the mouth and in the
      course of the thyroglossal duct. Rare localizations are intrathoracic
      (mediastinal, cardiac, pulmonary) and sub-diaphragmatic (including the adrenals,
      liver, gall bladder, and gastrointestinal tract). The most important differential
      diagnosis of ectopic thyroid is metastasis of differentiated thyroid carcinoma.By
      contrast, the term parathyroidectopy is not uniformly defined. Usually, the
      cervical-central localizations are referred to as "positional variants" (with the
      exception of the maxillary sinus and high parapharyngeal), whereas the cervical
      lateral localizations (carotid sheath, vagus nerve) and those below the
      brachiocephalic and mediastinal positions (extraligamentary, aortopulmonary
      window, paravagal) and other rare localizations are classified as "ectopic
      parathyroid tissue". Parathyroidectomy is very common (in autopsy studies in 28
      to 42.8% of all humans). In the context of primary hyperparathyroidism (pHPT),
      there is a prevalence of 6.3 to 16% of ectopic hyperfunctional parathyroid tissue
      (predominantly adenomas), which play an important role in the surgical treatment
      of pHPT.

PMID- 30105612
TI  - Integrating the Hopelessness Model and the Response Style Theory in an Adolescent
      Sample.
AB  - Integrations of cognitive models of depression, specifically, the hopelessness
      model (Abramson et al. Psychological Bulletin, 96, 358-372, 1989) and the
      response style theory (Nolen-Hoecksema et al. Journal of Abnormal Psychology,
      101, 405-422, 1992) have been suggested but no previous study has compared the
      integrations of these models with each other and the original models. Further,
      previous studies only tested the associations between composite scores of
      inferences, from the hopelessness model, and rumination (incl. brooding and
      reflection), from the response style theory. Thus, a 3-wave study using self
      report instruments with 519 adolescents was conducted (mean ageWave 1 = 16.09
      years; SD = 0.70; 62.7% female; 72.8% European American, 14.7% African-American,
      5.4% Latino, 4.4% mixed race/ethnicity, 1.4% Asian/Pacific Islander, 0.8% Native
      American, and 0.6% identified as "other"). The school serves predominantly
      working to middle class families and almost one third of the students were
      eligible for free or reduced lunch programs. AMOS and RMediation were used to
      calculate and compare five different theory-driven models. The findings of the
      study provide support for an integrated model in which both brooding and
      reflection are influenced by individual inferences and interact with individual
      inferences while affecting depressive symptoms. In addition, reflection plays an
      unexpectedly important role in this integrated model. Age and cognitive
      development are discussed as possible explanations for this finding.

PMID- 30105611
TI  - [Heterotopic tissue in the gastrointestinal tract].
AB  - Heterotopia of the gastrointestinal tract is a common finding. This is due to the
      complex embryogenesis and the relative ease to detect heterotopic tissue during
      endoscopy. The reason for biopsy is mostly to rule out neoplasms or to define
      specific causes of inflammation. Heterotopic tissue can occur in any location of
      the gastrointestinal tract. The most frequent are gastric heterotopia, pancreatic
      heterotopia, and heterotopia of Brunner's gland. On rare occasions, heterotopic
      tissue of salivary gland type as well as heterotopias of apocrine glands,
      thyroid, and prostatic tissue have been described. The most frequently involved
      organs are the small intestine, in particular the duodenum, the esophagus, and
      the stomach. Heterotopia of the large bowel occurs exclusively in the rectum.
      Most heterotopias do not cause symptoms and are easily diagnosed by biopsy and
      histology. However, depending on location, size, and the kind of underlying
      heterotopic tissue, they may cause significant complications, such as
      inflammation, ulceration and perforation, obstruction, intussusception, and
      severe life-threatening bleeding. Another rare but significant complication is
      neoplasia. Gastric heterotopias may give rise to pyloric gland adenomas within
      the bowel or rarely adenocarcinomas of the esophagus. Pancreatic heterotopia can
      be complicated by ductal type pancreatic adenocarcinomas, by acinus cell
      carcinomas, by intraductal papillary mucinous neoplasias, and also by endocrine
      tumors. The present paper summarizes our current knowledge about heterotopias in
      a topographic clinico-pathological manner.

PMID- 30105613
TI  - Correlation of serum levels and gene expression of tumor necrosis factor-alpha
      induced protein-8 like-2 with Parkinson disease severity.
AB  - Different immune-mediated mechanisms involved in the pathogenesis of Parkinson
      disease (PD) as a neurodegenerative and inflammatory disease. According to our
      knowledge, there is no report evaluating Tumor necrosis factor-alpha-induced
      protein-8 like-2 (TIPE2), a cytokine maintaining immune homeostasis, in PD. We
      analyzed the correlation of the serum levels and circulatory gene expression of
      TIPE2 with severity of PD. In this case-control study, 43 patients with PD and 40
      healthy subjects were enrolled. The diagnosis of PD was performed byclinical
      diagnostic criteria of the UK Parkinson's Disease Society Brain Bank. The
      severity of PD was evaluated by modified Hoehn and Yahr (H and Y) scale. Serum
      levels and gene expression of TIPE2 were assessed by Elisa and real time PCR,
      respectively. The mean serum levels and gene expression of TIPE2 in patients with
      PD did not have significant difference compared to healthy subjects. Linear
      multiple regression analysis showed that increased serum levels of TIPE2 are
      positively related to age and severity of PD (P <= 0.0001). In addition, the gene
      expression of TIPE2 was found to be associated with age (P < 0.0001). Our study
      showed that the serum levels of TIPE2 and its gene expression might be important
      prognostic biomarkers of PD.

PMID- 30105614
TI  - Donepezil improves the cognitive impairment in a tree shrew model of Alzheimer's
      disease induced by amyloid-beta1-40 via activating the BDNF/TrkB signal pathway.
AB  - Alzheimer's disease (AD) is a chronic neurodegenerative disorder which can
      contribute to memory loss and cognitive damage in the elderly; moreover, evidence
      from clinical and animal studies demonstrated that AD always exhibit severe
      cognitive deficits. However, the effects of donepezil medications on cognition
      are controversial. Additionally, it is unclear whether donepezil can protect
      neurons to improve cognitive function through the brain-derived neurotropic
      factor (BDNF)/tyrosine receptor kinase B (TrkB) signalling pathway in the tree
      shrew (TS), which has a closer evolutionary relationship to primates than
      rodents. Here, we designed a study on an amyloid-beta1-40 (Abeta1-40)-induced TS
      model of AD and investigated the molecular mechanism by which donepezil protects
      neurons and improves cognitive function through activating the BDNF/TrkB
      signalling pathway. The results showed that donepezil could rescue Abeta1-40
      induced spatial cognition deficits, and reverse Abeta1-40-induced temporal horn
      along with ADC enlargement in the TS brain. Meanwhile, it suppressed Abeta1-40
      induced neuronal damage and loss of body weight. Intriguingly, donepezil could
      increase the choline acetyl transferase (ChAT) expression level and reduce the
      fibrillary acid protein (GFAP) expression level in the hippocampus and cortex of
      TS. Additionally, donepezil significantly upregulated the expression level of
      BDNF, as well as the phosphorylated level of TrkB. These results suggested that
      donepezil could protect neurocytes from senility and ameliorate learning and
      memory impairment in the TS model of AD, which appeared to be through regulating
      the cholinergic system and inhibiting the BDNF/TrkB-dependent signalling pathway.
      Moreover, the study underlines the potency of TS to be a novel animal model for
      research on AD, and it deserves intensive attention.

PMID- 30105618
TI  - Perceived Discrimination, Coping Mechanisms, and Effects on Health in Bisexual
      and Other Non-Monosexual Adults.
AB  - Bisexual individuals experience unique discrimination related to their sexual
      orientation, which may increase their risk of adverse health outcomes. The study
      goal was to investigate how bisexual and other non-monosexual individuals
      experience discrimination, understand how they perceive discrimination to affect
      their health, and examine the ways in which they cope with discrimination by
      analyzing responses to open-ended survey questions. The sample included 442
      bisexual and other non-monosexual adults, ages 18-68 years (M = 28.97, SD =
      10.30), who either reported a bisexual identity or reported attractions to more
      than one gender. Gender identities included women (n = 347), men (n = 42), and
      transgender/non-binary individuals (n = 53); 29% of participants were currently
      located outside of the U.S. Participants completed an online survey, including
      three open-ended questions regarding their experiences with discrimination, how
      discrimination affects their health, and methods used to cope with
      discrimination. Themes related to perceived discrimination included: double
      discrimination of bisexuals and other non-monosexual individuals by
      heterosexuals, lesbian and gay individuals; bisexual invalidation and erasure;
      and sexual victimization. Themes related to the perceived effects of
      discrimination on health included: impact on mental health; impact on physical
      health; and effect of discrimination in healthcare. Themes related to coping with
      discrimination included: social support; resilience; and identity-specific media
      consumption. Findings demonstrate that bisexual and other non-monosexual
      individuals' experiences of discrimination can be additive, based on other
      marginalized facets of identity, including race/ethnicity, gender, and
      socioeconomic status. Our findings have implications for advancing bisexual
      health research from an intersectionality framework.

PMID- 30105615
TI  - Pharmacological inhibition of store-operated calcium entry in MDA-MB-468 basal A
      breast cancer cells: consequences on calcium signalling, cell migration and
      proliferation.
AB  - Store-operated Ca2+ entry is a pathway that is remodelled in a variety of
      cancers, and altered expression of the components of store-operated Ca2+ entry is
      a feature of breast cancer cells of the basal molecular subtype. Studies of store
      operated Ca2+ entry in breast cancer cells have used non-specific pharmacological
      inhibitors, complete depletion of intracellular Ca2+ stores and have mostly
      focused on MDA-MB-231 cells (a basal B breast cancer cell line). These studies
      compared the effects of the selective store-operated Ca2+ entry inhibitors
      Synta66 and YM58483 (also known as BTP2) on global cytosolic free Ca2+
      ([Ca2+]CYT) changes induced by physiological stimuli in a different breast cancer
      basal cell line model, MDA-MB-468. The effects of these agents on proliferation
      as well as serum and epidermal growth factor (EGF) induced migration were also
      assessed. Activation with the purinergic receptor activator adenosine
      triphosphate, produced a sustained increase in [Ca2+]CYT that was entirely
      dependent on store-operated Ca2+ entry. The protease activated receptor 2
      activator, trypsin, and EGF also produced Ca2+ influx that was sensitive to both
      Synta66 and YM58483. Serum-activated migration of MDA-MB-468 breast cancer cells
      was sensitive to both store-operated Ca2+ inhibitors. However, proliferation and
      EGF-activated migration was differentially affected by Synta66 and YM58483. These
      studies highlight the need to define the exact mechanisms of action of different
      store-operated calcium entry inhibitors and the impact of such differences in the
      control of tumour progression pathways.

PMID- 30105617
TI  - Risk Perception and Interest in HIV Pre-exposure Prophylaxis Among Men Who Have
      Sex with Men with Rectal Gonorrhea and Chlamydia Infection.
AB  - Rectal gonorrhea and chlamydia infections are associated with significantly
      increased risk of HIV transmission among gay, bisexual, and other men who have
      sex with men (MSM). MSM diagnosed with rectal gonorrhea or chlamydia may benefit
      from pre-exposure prophylaxis (PrEP) for HIV prevention. We analyzed HIV risk
      perception, PrEP interest, and sexually transmitted infection (STI) test results
      among MSM presenting to a publicly funded STI clinic from 2014 to 2016. A total
      of 401 MSM were tested for rectal STIs during the study period: 18% were
      diagnosed with rectal gonorrhea or chlamydia infection. Patients who perceived
      themselves to be at medium or high risk for HIV were significantly more likely to
      express interest in PrEP compared to those who reported low or no perceived risk
      (OR 1.88, 95% CI 1.13-3.11; p = .014). However, there was no significant
      difference in perceived HIV risk between those who were diagnosed with a rectal
      STI and those who were not. Although rectal STIs are a significant risk factor
      for HIV infection, MSM diagnosed with a rectal STI did not perceive themselves to
      be at increased risk for HIV infection, indicating a potential barrier to
      successful PrEP implementation in this population.

PMID- 30105619
TI  - Trajectories of Suicidal Ideation from Adolescence to Adulthood: Does the History
      of Same-Sex Experience Matter?
AB  - The fluidity of same-sex experience (SSE) can be conceptualized as both a risk
      and a resource that impacts suicidal ideation over time. Considering whether SSE
      occurs in adolescence, adulthood, or both, this study suggests that SSE in both
      adolescence and adulthood is associated with depression and low self-esteem
      throughout the life course, resulting in chronic susceptibility to suicidal
      ideation. Yet due to variation in both accumulation of risk and resources over
      time, trajectories of suicidal ideation during the transition to adulthood likely
      vary by timing of SSE. To test these hypotheses, we fit latent growth curve
      models to a gender-stratified sample taken from the National Longitudinal Study
      of Adolescent to Adult Health (7608 men, 8070 women). We created four groups of
      SSE: no SSE (6322 men, 5981 women), SSE in adolescence only (634 men, 480 women),
      SSE in adulthood only (372 men, 1081 women), and SSE in adolescence and adulthood
      (280 men, 528 women). Men and women with SSE in both life stages had the greatest
      risk of suicidal ideation in adolescence and in adulthood. Yet women with first
      SSE in adulthood had less of a decline in suicidal ideation over time, relative
      to those with no SSE and those with SSE in adolescence only, and this was
      partially due to higher depression and lower self-esteem. Results suggest greater
      support is needed for adolescents expressing non-normative sexualities and for
      those with first SSE in adulthood, a group that is more difficult to identify in
      schools.

PMID- 30105616
TI  - Roles of melatonin and its receptors in cardiac ischemia-reperfusion injury.
AB  - Acute myocardial infarction (AMI) has been an economic and health burden in most
      countries around the world. Reperfusion is a standard treatment for AMI as it can
      actively restore blood supply to the ischemic site. However, reperfusion itself
      can cause additional damage; a process known as cardiac ischemia/reperfusion
      (I/R) injury. Although several pharmacological interventions have been shown to
      reduce tissue damage during I/R injury, they usually have undesirable effects.
      Therefore, endogenous substances such as melatonin have become a field of active
      investigation. Melatonin is a hormone that is produced by the pineal gland, and
      it plays an important role in regulating many physiological functions in human
      body. Accumulated data from studies carried out in vitro, ex vivo, in vivo, and
      also from clinical studies have provided information regarding possible
      beneficial effects of melatonin on cardiac I/R such as attenuated cell death, and
      increased cell survival, leading to reduced infarct size and improved left
      ventricular function. This review comprehensively discusses and summarizes those
      effects of melatonin on cardiac I/R. In addition, consistent and inconsistent
      reports regarding the effects of melatonin in cases of cardiac I/R together with
      gaps in surrounding knowledge such as the appropriate onset and duration of
      melatonin administration are presented and discussed. From this review, we hope
      to provide important information which could be used to warrant more clinical
      studies in the future to explore the clinical benefits of melatonin in AMI
      patients.

PMID- 30105620
TI  - Long-Term Health Outcome and Quality of Life Post-HSCT for IL7Ralpha-, Artemis-,
      RAG1- and RAG2-Deficient Severe Combined Immunodeficiency: a Single Center
      Report.
AB  - Hematopoietic stem cell transplantation (HSCT) is curative for severe combined
      immunodeficiency (SCID), but data on long-term impact of pre-HSCT chemotherapy,
      immune reconstitution and quality of life (QoL) of specific SCID genotypes are
      limited. We evaluated the long-term immune-reconstitution, health outcome and QoL
      in IL7Ralpha SCID, Artemis and RAG1 and 2 SCID survivors > 2 years post-HSCT in
      our center. Clinical data and immune reconstitution parameters were collated, and
      patients/families answered PedsQL generic core scale v4.0 questionnaires. Thirty
      nine patients with a diagnosis of IL7Ralpha SCID (17 patients), Artemis SCID (8
      patients) and RAG1/2 SCID (13 patients) had undergone HSCT with median age at
      last follow up for IL7Ralpha SCID, 14 years (range 4-27) and Artemis and RAG1/2
      SCID, 10 years (range 2-18). Many patients have ongoing medical issues at latest
      follow-up [IL7Ralpha (73%), Artemis (85%), RAG1/2 (55%)]. Artemis SCID patients
      experienced more sequela than RAG1/2 SCID. Conditioned recipients with Artemis
      and RAG SCID had more CD4+ naive lymphocytes compared to unconditioned
      recipients. All patients except those of IL7Ralpha SCID reported lower QoL;
      further subset group analysis showed parents and Artemis and RAG1/2 survivors
      without ongoing medical issues reported normal QoL. Conditioned recipients have
      superior long-term thymopoiesis, chimerism and immunoglobulin-independence. QoL
      was normal in those who did not have medical issues at long-term follow-up.

PMID- 30105621
TI  - A survey on practices for active surveillance of carriage of multidrug-resistant
      bacteria in hospitals in the Autonomous Community of Valencia, Spain.
AB  - A questionnaire-based cross-sectional study was conducted to gather information
      on current microbiological practices for active surveillance of carriage of
      multidrug-resistant (MDR) bacteria in hospitals from 14 health departments of the
      Autonomous Community of Valencia (ACV), Spain, which together provided medical
      attention to 3,271,077 inhabitants in 2017, approximately 70% of the population
      of the ACV. The survey consisted of 35 questions on MDR bacteria screening
      policies, surveillance approach chosen (universal vs. targeted), and
      microbiological methods and processes in use for routine detection and reporting
      of colonization by MDR bacteria, including the anatomical sites scheduled to be
      sampled for each MDR bacterial species, and the methodology employed (culture
      based, molecular-based, or both). Our study revealed striking differences across
      centers, likely attributable to the lack of consensus on optimal protocols for
      sampling, body sites for screening, and microbiological testing, thus
      underscoring the need for consensus guidelines on these issues.

PMID- 30105623
TI  - Analysis of thermally labile pesticides by on-column injection gas chromatography
      in fruit and vegetables.
AB  - Thermally labile pesticides (captafol, captan, dicofol, and folpet) are highly
      prone to suffer thermal degradation during sample introduction into a gas
      chromatograph (GC) to tetrahydrophthalimide (THPI), 4,4'-dichlorobenzophenone
      (DCBP), and phthalimide (PI), respectively, mainly produced in the glass liner of
      the injector. This undesired behavior leads to inaccurate qualitative and
      quantitative results. Direct on-column injection (OCI) technique is evaluated as
      an alternative to avoid or minimize compound alteration during the analysis. This
      configuration was studied and evaluated for the determination of this group of
      thermally troublesome pesticides. The OCI inlet was operated in "track oven"
      temperature and connected to a wide-bore deactivated guard column that is itself
      connected to a capillary GC analytical column. This technique has demonstrated to
      be useful for avoiding degradation generated in the hot inlet. Limitations
      observed for OCI in routine analysis were injection volume, guard column length,
      and maintenance issues. Analytical standards spiked in vegetable solutions were
      injected in OCI, not observing any thermal degradation rate. On the contrary,
      classical splitless injection (SLI) produced high degradation rates in all cases.
      This OCI approach was validated in citrate QuEChERS extracts of tomato, apple,
      and orange matrices for these four compounds and their corresponding
      transformation products (THPI, DCBP, and PI), evaluating recoveries,
      repeatability, linearity, and matrix effect. This set-up enabled the correct
      identification and quantitation for most compounds at LOQs of 0.010 mg/kg in
      fruit and vegetable samples. The OCI grants evident differentiation between
      metabolites naturally occurring in food and thermal degradation products created
      during the analysis. Graphical abstract ?.

PMID- 30105624
TI  - 13C quantification in heterogeneous multiphase natural samples by CMP-NMR using
      stepped decoupling.
AB  - Many natural and environmental samples contain combinations of liquids, gels, and
      solids, yet quantification in the intact state and across multiple phases is
      highly challenging. Comprehensive multiphase nuclear magnetic resonance (CMP-NMR)
      combines all the capabilities of high-resolution magic angle spinning (HR-MAS),
      with the addition of full solids power handling, permitting all phases (i.e.,
      mixtures of liquids, gels, and solids) to be studied and differentiated in intact
      samples without pre-treatment or extraction. Here, quantification in CMP-NMR is
      considered. As 1H NMR is considerably broadened in the solid-state,
      quantification is easier to achieve through 13C which can be observed easily in
      all the phases. Accurate 13C quantification requires effective 1H decoupling for
      all the phases, but each phase requires different decoupling conditions. To
      satisfy these conditions, a pulse sequence termed stepped decoupling is
      introduced. This sequence can be used to study all components under ideal
      decoupling conditions resulting in high-resolution spectra without truncation
      artifacts and provides accurate integrals of components in all phases. The
      approach is demonstrated on standards and then applied to natural samples
      including broccoli, soil, and Arabidopsis. The approach permits accurate
      quantification of chemical categories (for example total carbohydrates) as well
      as individual species (for example glucose). Further, as the samples are studied
      intact, volatile species such as methanol and ethylene which are normally hard to
      detect in plants can be easily quantified in Arabidopsis. Graphical abstract ?.

PMID- 30105622
TI  - Magnetic resonance spectroscopy in very preterm-born children at 4 years of age:
      developmental course from birth and outcomes.
AB  - PURPOSE: Brain metabolites show very rapid maturation over infancy, particularly
      following very preterm (VPT) birth, and can provide an index of brain injury. The
      utility of magnetic resonance imaging (MRS, magnetic resonance spectroscopy) in
      predicting outcome in VPT-born infants is largely limited to 2-year outcomes. We
      examined the value of MRS in VPT followed longitudinally to 4 years. METHODS: MRS
      datasets were acquired in 45 VPT infants (< 32 weeks gestational age)
      longitudinally: at birth, at term-equivalent and at 4 years of age. Using LCModel
      analyses in a basal ganglia voxel, we investigated metabolite ratios as a
      function of age, brain injury and outcome. We also studied a full-term (FT)
      cohort at 4 years and compared group differences with outcome. RESULTS: We found
      significant age-related changes in many brain metabolites in infancy, including
      phosphocreatine (CR)/phosphocholine (CHO), N-acetylaspartylglutamate (NAA)/CHO,
      myoinositol (INS)/CHO and INS/CR; there were no significant MRS differences
      between VPT and FT groups at 4 years of age, or differences at 4 years as a
      function of early brain injury or outcome. The rate of change in metabolite
      ratios from VPT birth to term-equivalent age did not predict outcome in the VPT
      children at 4 years. CONCLUSION: Brain metabolite ratios measured in VPT-born
      infants have shown associations with short-term outcomes, but these correlations
      did not extend to early childhood nor predict cognitive sequelae. The most
      frequently reported poor outcome in VPT-born children is cognitive difficulties
      starting at early school age. MRS metrics early in the infant's life do not
      appear to predict these longer-term outcomes.

PMID- 30105626
TI  - Double-barrel STA to proximal MCA bypass and proximal parent artery occlusion for
      a fusiform superior clinoidal ICA aneurysm.
AB  - BACKGROUND: Blood flow replacement and parent artery occlusion are alternative
      treatments of complex fusiform superior clinoidal ICA aneurysms. While double
      barrel STA to proximal MCA bypass is a conventional approach among these reported
      bypass algorithms, its technical details remain underexplored. METHOD: We have
      applied the double-barrel STA to proximal MCA bypass and parent artery occlusion
      to treat a 45-year-old female patient with a right fusiform superior clinoidal
      ICA aneurysm. The technical nuances of this approach are reported. CONCLUSION: We
      show that double-barrel STA to proximal MCA bypass and proximal parent artery
      occlusion can be alternative treatments of complex fusiform superior clinoidal
      ICA aneurysms.

PMID- 30105625
TI  - A fluorometric sensing method for sensitive detection of trypsin and its
      inhibitor based on gold nanoclusters and gold nanoparticles.
AB  - In this work, a facile, label-free, and sensitive fluorometric strategy for
      detection of trypsin and its inhibitor was established on the basis of the
      fluorescence resonance energy transfer (FRET) between mercaptoundecanoic acid
      functionalized gold nanoclusters (AuNCs) and gold nanoparticles (AuNPs) via
      protamine as a bridge. Protamine can trigger the aggregation of AuNPs and link
      AuNCs with aggregated AuNPs through electrostatic interaction. Compared with
      monodisperse AuNPs, the UV-vis absorption band of aggregated AuNPs overlapped
      considerably with the emission spectrum of AuNCs. Thus, the fluorescence of AuNCs
      was obviously quenched by the aggregated AuNPs through FRET. In the presence of
      trypsin, protamine was hydrolyzed into small fragments, leading to the
      deaggregation of AuNPs and breaking of the short distance between AuNPs and
      AuNCs, so the FRET process was inhibited, and the fluorescence of AuNCs was
      recovered. The increase in the fluorescence intensity of AuNCs was directly
      related to the amount of trypsin. Hence trypsin can be determined on the basis of
      the variation of fluorescence intensity, with a linear range of 5-5000 ng mL-1
      and a detection limit of 1.9 ng mL-1. In addition, this system was used for the
      detection of trypsin inhibitor by application of the inhibitor isolated from
      soybean as a model. The sensing method was applied for trypsin detection in human
      urine and commercial multienzyme tablet samples with satisfactory results.
      Graphical abstract ?.

PMID- 30105628
TI  - Neuromuscular Junction Morphology and Gene Dysregulation in the Wobbler Model of
      Spinal Neurodegeneration.
AB  - Amyotrophic lateral sclerosis (ALS) is the most common adult-onset neuromuscular
      disease for which there is currently no effective treatment. The progression of
      ALS includes loss of motor neurons controlling the voluntary muscles, with much
      of this loss occurring at the neuromuscular junction. In an effort to better
      understand changes at the neuromuscular junction, we utilized the wobbler mouse
      model of motor neuron loss. We examined biceps and end plate morphologies and
      monitored selected factors involved in end plate function. Structural volumes
      were determined from 3D reconstructions that were generated for the end plates.
      Wobbler mice exhibited size reductions of both the muscle fibers and the end
      plates within the biceps, and we found that the end plate volumes were the most
      sensitive indicator of the degeneration. Concurrently, we found increases in
      calcitonin gene-related peptide (CGRP) and its receptor in wobbler biceps and
      spinal cord. We also found increases in gene expression of two acetylcholine
      receptors within the wobbler biceps, which may be a result of altered CGRP/CALCRL
      (calcitonin receptor-like receptor) expression.

PMID- 30105629
TI  - Immunomodulatory Roles of PACAP and VIP: Lessons from Knockout Mice.
AB  - A bidirectional cross-talk is established between the nervous and immune systems
      through common mediators including neuropeptides, neurotransmitters, and
      cytokines. Among these, PACAP and VIP are two highly related neuropeptides widely
      distributed in the organism with purported immunomodulatory actions. Due to their
      well-known anti-inflammatory properties, administration of these peptides has
      proven to be beneficial in models of acute and chronic inflammatory diseases.
      Nevertheless, the relevance of the endogenous source of these peptides in the
      modulation of immune responses remains to be elucidated. The development of
      transgenic mice with specific deletions in the genes coding for these
      neuropeptides (Vip and Adcyap1) or for their G-protein-coupled receptors VPAC1,
      VPAC2, and PAC1 (Vipr1, Vipr2, Adcyap1r1) has allowed to address this question,
      underscoring the complexity of the immunoregulatory properties of PACAP and VIP.
      The goal of this review is to integrate the existing information on the immune
      phenotypes of mice deficient for PACAP, VIP, or their receptors, to provide a
      global view on the roles of these endogenous neuropeptides during immunological
      health and disease.

PMID- 30105627
TI  - Severe atypical pneumonia in critically ill patients: a retrospective multicenter
      study.
AB  - BACKGROUND: Chlamydophila pneumoniae (CP) and Mycoplasma pneumoniae (MP) patients
      could require intensive care unit (ICU) admission for acute respiratory failure.
      METHODS: Adults admitted between 2000 and 2015 to 20 French ICUs with proven
      atypical pneumonia were retrospectively described. Patients with MP were compared
      to Streptococcus pneumoniae (SP) pneumonia patients admitted to ICUs. RESULTS: A
      total of 104 patients were included, 71 men and 33 women, with a median age of 56
      [44-67] years. MP was the causative agent for 76 (73%) patients and CP for 28
      (27%) patients. Co-infection was documented for 18 patients (viruses for 8 [47%]
      patients). Median number of involved quadrants on chest X-ray was 2 [1-4], with
      alveolar opacities (n = 61, 75%), interstitial opacities (n = 32, 40%). Extra
      pulmonary manifestations were present in 34 (33%) patients. Mechanical
      ventilation was required for 75 (72%) patients and vasopressors for 41 (39%)
      patients. ICU length of stay was 16.5 [9.5-30.5] days, and 11 (11%) patients died
      in the ICU. Compared with SP patients, MP patients had more extensive
      interstitial pneumonia, fewer pleural effusion, and a lower mortality rate [6
      (8%) vs. 17 (22%), p = 0.013]. According MCA analysis, some characteristics at
      admission could discriminate MP and SP. MP was more often associated with
      hemolytic anemia, abdominal manifestations, and extensive chest radiograph
      abnormalities. SP-P was associated with shock, confusion, focal crackles, and
      focal consolidation. CONCLUSION: In this descriptive study of atypical bacterial
      pneumonia requiring ICU admission, mortality was 11%. The comparison with SP
      pneumonia identified clinical, laboratory, and radiographic features that may
      suggest MP or CP pneumonia.

PMID- 30105630
TI  - Positive correlation between sarcopenia and elevation of neutrophil/lymphocyte
      ration in pathological stage IIIA (N2-positive) non-small cell lung cancer
      patients.
AB  - OBJECTIVE: Surgical indication in stage IIIA (N2) non-small cell lung cancer is
      still controversial. Hence, there is a need for the identification of predictors
      of the postoperative outcome in these patients. Although sarcopenia is expected
      to be a novel predictor of postoperative outcome in these patients, the
      underlying clinical features of sarcopenia have not been well investigated.
      Elevation of neutrophil/lymphocyte ratio indicates cancer-associated inflammation
      and depression of anticancer immunity. We analyzed the influence of sarcopenia on
      postoperative prognosis, and investigated the relationship between sarcopenia and
      neutrophil/lymphocyte ratio in patients with stage IIIA (N2) non-small cell lung
      cancer. METHODS: We retrospectively investigated 69 patients with stage IIIA (N2)
      non-small cell lung cancer. We used the L3 muscle index as a clinical measurement
      of sarcopenia, and divided patients into the sarcopenic (n = 21) and the non
      sarcopenic group (n = 48). We then investigated the effect of sarcopenia on
      postoperative prognosis, and evaluated the correlation between sarcopenia and
      neutrophil/lymphocyte ratio. RESULTS: This study included 47 males and 22
      females. Univariate analysis revealed that sarcopenia, performance status, and
      serum cytokeratin-19 fragment level were predictors of poor prognosis;
      multivariate analysis revealed that performance status and sarcopenia were
      independent predictors of poor prognosis. The presence of sarcopenia was
      significantly correlated with neutrophil/lymphocyte ratio elevation. CONCLUSIONS:
      Sarcopenia is a novel predictor of poor prognosis in patients with stage IIIA
      (N2) non-small cell lung cancer. Neutrophil/lymphocyte ratio elevation might be
      the reason for poor prognosis in sarcopenic patients.

PMID- 30105632
TI  - Refractory Arrhythmias in a Young Patient Poisoned by Imipramine.
AB  - Tricyclic antidepressants are used to treat a variety of mental disorders, and
      are considered a common cause of fatal drug poisoning. This study reports a young
      woman with no history of cardiac diseases who presented to the emergency
      department with heart palpitation, weakness, and lethargy. After a short period
      of time, she became unconscious and experienced hypotension and refractory
      arrhythmia, finally being diagnosed with imipramine poisoning. Accurate history
      taking and the possible causes of these complications including cardio-toxic drug
      poisoning should be considered in such patients.

PMID- 30105631
TI  - Lysine-specific demethylase 1 cooperates with BRAF-histone deacetylase complex 80
      to enhance HIV-1 Tat-mediated transactivation.
AB  - Despite the notable success of combination antiretroviral therapy, how to
      eradicate latent HIV-1 from reservoirs poses a challenge. The Tat protein plays
      an indispensable role in HIV reactivation and histone demethylase LSD1 promotes
      Tat-mediated long terminal repeats (LTR) activation. However, the role of LSD1 in
      remodeling chromatin and the role of its component BHC80 in activation of latent
      HIV-1 in T cells are unknown. Our findings indicate that LSD1 could decrease the
      level of histone H3 lysine 4 trimethylation (H3K4me3) at the HIV-1 promoter by
      recruiting histone lysine demethylase 5A (KDM5A) and preventing histone
      methyltransferase Set1A and WD-40 repeat protein 5 (WDR5) from binding to LTR.
      Moreover, BHC80 is necessary for LSD1-triggered LTR activation and assists LSD1
      in activating LTR by binding to nucleotides 305-631 of LTR. In activated J-Lat-A2
      cells, BHC80 expression was elevated and its isoform BHC80-6 promoted the
      association of BHC80 with LSD1. These results suggest that the LSD1-BHC80 complex
      enhances HIV-1 transcription by a decrease of H3K4me3 level at the viral
      promoter. Therefore, it might be used as a new drug target to reactivate latent
      HIV-1.

PMID- 30105633
TI  - Chip-on-tip endoscope incorporating a soft robotic pneumatic bending
      microactuator.
AB  - In the ever advancing field of minimally invasive surgery, flexible instruments
      with local degrees of freedom are needed to navigate through the intricate
      topologies of the human body. Although cable or concentric tube driven solutions
      have proven their merits in this field, they are inadequate for realizing small
      bending radii and suffer from friction, which is detrimental when automation is
      envisioned. Soft robotic actuators with locally actuated degrees of freedom are
      foreseen to fill in this void, where elastic inflatable actuators are very
      promising due to their S3-principle, being Small, Soft and Safe. This paper
      reports on the characterization of a chip-on-tip endoscope, consisting out of a
      soft robotic pneumatic bending microactuator equipped with a 1.1 * 1.1 mm2 CMOS
      camera. As such, the total diameter of the endoscope measures 1.66 mm. To show
      the feasibility of using this system in a surgical environment, a preliminary
      test on an eye mock-up is conducted.

PMID- 30105634
TI  - Safety and Feasibility of Linear Stapling Device with Bioabsorbable Polyglycolic
      Acid Sheet for Duodenal Closure in Gastric Cancer Surgery: A Multi-institutional
      Phase II Study.
AB  - BACKGROUND: Duodenal stump fistula (DSF) after gastrectomy is of low frequency
      but a critical complication in gastric cancer surgery. Manual oversewing for
      reinforcement of the duodenal stump is not applicable when free longitudinal
      margin is short and has technical difficulties in laparoscopic surgery. This
      trial evaluated the safety and feasibility of using a linear stapler with
      bioabsorbable polyglycolic acid (PGA) sheet for duodenal stump closure and
      reinforcement in gastric cancer surgery. METHODS: This multi-institutional,
      prospective phase II trial included gastric cancer patients who were scheduled to
      undergo distal or total gastrectomy with R-Y reconstruction. In all cases,
      duodenum was transected using a linear stapler with PGA sheet. The primary
      endpoint was the incidence of postoperative DSF. Sample size was set at 100
      patients considering an expected value of 3% and threshold value of 8% with one
      sided testing at a 10% significance level. RESULTS: Between June 2014 and June
      2015, a total of 100 patients were registered in this trial. Postoperative DSF
      was observed in two cases (2.0%, 90% CI 0.4-6.2%) which was developed on
      postoperative days 13 and 20. Intraoperative bleeding at the duodenal stump
      staple line was observed in one case but was easily controlled without additional
      suturing. Postoperative bleeding was not observed in any of the cases.
      CONCLUSION: This study suggested that the use of PGA sheet as a reinforcement
      material for closure of the duodenal stump during gastrectomy for gastric cancer
      is both safe and feasible. Trial registration number UMIN 000014398.

PMID- 30105635
TI  - Usability of Intraoperative Fluorescence Imaging with Indocyanine Green During
      Laparoscopic Cholecystectomy After Percutaneous Transhepatic Gallbladder
      Drainage.
AB  - BACKGROUND: Patients with persistent symptoms of acute cholecystitis for >72 h
      who cannot undergo urgent laparoscopic cholecystectomy (LC) often undergo
      percutaneous transhepatic gallbladder drainage (PTGBD) and delayed LC. However,
      intraoperative near-infrared fluorescence with indocyanine green (ICG) has
      recently become available in various surgical settings. Therefore, we evaluated
      the usability of intraoperative fluorescence imaging with ICG for LC after PTGBD
      in patients with acute cholecystitis. METHODS: The preoperative and postoperative
      clinical characteristics of patients who underwent LC after PTGBD were
      retrospectively analyzed. RESULTS: In total, 130 patients were reviewed.
      Intraoperative ICG fluorescence imaging was used in 39 (30.0%) patients, and none
      developed adverse reactions. Patients with ICG fluorescence imaging had a
      significantly shorter operative time (129 +/- 46 vs. 150 +/- 56 min, p = 0.0455),
      markedly lower conversion rate (2.6% vs. 22.0%, p = 0.0017), and lower proportion
      of subtotal cholecystectomy (0.0% vs. 6.6%, p = 0.0359) than patients without ICG
      fluorescence imaging. Independent risk factors for conversion to laparotomy
      during LC after PTGBD were the performance of PTGBD after 48 h from onset (OR
      3.52; 95% CI 1.11-12.21; p = 0.0322), an unremoved PTGBD tube on LC (4.48, 1.46
      15.00, p = 0.0084), and surgery without ICG (8.00, 1.28-159.47, p = 0.0231).
      CONCLUSION: Intraoperative ICG fluorescence imaging produced better surgical
      outcomes without any adverse reactions. Early performance of PTGBD and
      intraoperative ICG fluorescence imaging can reduce the surgical difficulties in
      LC after PTGBD for acute cholecystitis.

PMID- 30105636
TI  - Cognitive Assessment of Surgeons During Surgical Procedures: Influence of Time
      and Intraoperative Complications.
AB  - INTRODUCTION: Surgeon's performance may be influenced by several factors that may
      affect skills and judgement, which ultimately represents surgeon's cognition.
      Cognition refers to all forms of knowing and awareness, such as perceiving,
      conceiving, remembering, reasoning, judging, imagining, and problem solving. This
      report aims to evaluate the effect of operative time and operative complications
      on surgeon's cognition. METHODS: Forty-six surgeons (mean age 31 years, 78%
      males) assigned to an operation expected to last for at least 2 h, volunteered
      for the study. All participants underwent 3 cognitive tests at the beginning of
      the operation and hourly, until the end of the procedure: (a) concentration
      (serial sevens, counting down from 100 by sevens); (b) visual (fast counting,
      counting the number of circles with the same color among a series of circles);
      and (c) motor (trail making, connecting a set of numbered dots). Intraoperative
      complications were recorded. RESULTS: The visual test had a stable behavior along
      time. Concentration and motor tests tend to be performed faster. Intraoperative
      complications occurred in 5 (11%) cases (3 hemorrhage and 2 organ injuries).
      Performance time was stable for concentration and motor tests but visual test
      tends to be performed faster in cases with an intraoperative complication.
      CONCLUSION: Our results showed that (1) time does not jeopardize surgeons'
      cognition, but rather surgeons learned to perform the tests faster, and (2)
      complications do not decrease surgeons' cognition.

PMID- 30105637
TI  - Health Literacy Among Surgical Patients: A Systematic Review and Meta-analysis.
AB  - Health literacy is the extent to which patients are able to understand and act
      upon health information. This concept is important for surgeons as their patients
      have to comprehend the nature, risks and benefits of surgical procedures, adhere
      to perioperative instructions, and make complex care decisions about
      interventions. Our review aimed to determine the prevalence of limited health
      literacy of the surgical patient population. A search of MEDLINE and EMBASE was
      performed from inception until January 14th 2017 for experimental and
      observational studies reporting surgical patients' health literacy measurement.
      Overall pooled proportion of surgical patients with limited health literacy was
      calculated using a random-effects model and methodologic quality was assessed. A
      total of 40 studies representing 18,895 surgical patients were included in our
      quantitative synthesis. Pooled estimate of limited health literacy was 31.7%
      (95%CI 24.7-39.2%, I2 99.0%). There was low risk of bias among the majority of
      the 51 studies included in the qualitative synthesis. Statistical heterogeneity
      could not be fully accounted for by methodologic quality or patient and surgical
      characteristics. However, some of the heterogeneity was accounted by measurement
      tool [combined proportions with the REALM and NVS of 35.6 (95%CI 31.5-39.9, I2
      73.0%)]. A number of different health literacy measurement tools were used (19
      overall). Our review demonstrates a high prevalence of limited health literacy
      among surgical patients with considerable heterogeneity. Our findings suggest the
      importance of recognizing and addressing surgical patients with limited health
      literacy and the need for standardization in measurement tools.

PMID- 30105638
TI  - Incidental Gallbladder Cancer: How Residual Disease Affects Outcome in Two
      Referral HPB Centers from South America.
AB  - BACKGROUND: Residual disease (RD) has been described as one of the most relevant
      prognostic factors after radical surgical resection for incidental gallbladder
      cancer (IGC). The purpose of the present study was to analyze patterns of RD and
      determinant prognostic factors in patients undergoing re-resection for IGC.
      METHODS: Patients undergoing re-exploration due to IGC between 1990 and 2014 were
      identified in two referral centers from different South-American countries.
      Patients submitted to a radical definitive operation were included in the study.
      Demographics and tumor-treated related variables were analyzed in correlation
      with RD and survival. The site of RD, local (gallbladder bed) or regional (lymph
      nodes and bile duct) was correlated with disease-specific survival (DSS).
      RESULTS: Of 265 patients with IGC submitted to surgery, 168 underwent a radical
      re-resection and RD was found in 58 (34.5%). Demographic, clinical and surgical
      variables were compared between both centers showing differences in type of
      resection, laparoscopic approach, T stages and disease stage. Location of RD was
      regional in 34 (20.2%) and local in 24 (14.3%), and no residual disease was found
      in 110 (65.5%) patients. T stage (T1b = 20%, T2 = 23.8%, T3 = 71.7%, p < 0.001)
      and disease stage (p < 0.001) were independent predictors of RD. Finding RD at
      any location reduced the DSS in comparison with non-RD patients (19.6 months vs.
      62.7 months p < 0.001). No differences in DSS according to the location of RD
      were found, and all anatomic sites were equally poor (p = 0.27). RD at any site
      predicted DSS (p < 0.001), independently of all other IGC variables. CONCLUSIONS:
      IGC presented similar clinical parameters in two different countries of South
      America. RD was demonstrated as the most critical prognostic variable in patients
      with IGC treated by a radical resection. The presence of RD was associated with
      poor outcome, independently of any anatomic location. Future studies
      incorporating neoadjuvant chemotherapy in the treatment of patients with
      prognostic factors for RD are required to improve survival in this entity.

PMID- 30105639
TI  - Subcutaneous Phaeohyphomycosis: A Clinical Mimic of Skin and Soft Tissue
      Neoplasms-A Descriptive Study from India.
AB  - BACKGROUND: Phaeohyphomycosis is a fungal infection caused by heterogenous group
      of fungi known as phaeoid or dematiaceous fungi. It manifests in four clinical
      forms-cutaneous, subcutaneous, systemic and cerebral phaeohyphomycosis. The
      subcutaneous form is the most common presentation. Clinically these subcutaneous
      swellings resemble benign skin and soft tissue neoplasms like lipoma, sebaceous
      cyst or neurofibroma. Histopathology serves as a very useful tool in diagnosing
      these cysts by identifying the fungal elements. METHODS: A retrospective review
      of all cases diagnosed as phaeohyphomycosis in the department of Pathology at a
      tertiary care centre in South India over 9 years (January 2009-December 2017) was
      done. The clinical, histopathological findings of these cases were reviewed and
      analysed. RESULTS: Sixty-six cases of subcutaneous phaeohyphomycosis were
      reported during the 9 year period. Sixty-two per cent of these patients were
      diagnosed as skin and soft tissue neoplasms. In 94% cases, the extremities were
      affected. Multiple cysts were seen in 11% of patients. Fine needle aspiration
      cytology was done in 29 cases with fungal hyphae identified in all cases on
      cytology. CONCLUSION: Subcutaneous phaeohyphomycosis mimics benign skin and soft
      tissue neoplasms clinically. Histopathological examination along with cytology
      plays a major role in diagnosis of phaeohyphomycosis and thus helps in
      appropriate patient management.

PMID- 30105640
TI  - The effect of exhaustive exercise on the choice of technique and physiological
      response in classical roller skiing.
AB  - PURPOSE: The aim of this study was to investigate the effect of exhaustive
      exercise on technique preference and the accompanying physiological response
      during classic skiing at constant workload, but with varying incline-speed
      combinations. METHODS: Seven male competitive cross-country skiers performed four
      tests, each lasting 23 min, at constant 200 W workload roller skiing on a
      treadmill using classic style, three in unfatigued state, and one after
      exhaustion. The incline and speed combination (that determined the 200 W) were
      altered each minute during the tests. The athletes were allowed to change sub
      technique at free will. Physiological variables and cycle rate were recorded
      continuously as well as the incline-speed combinations at which the sub-technique
      was changed. RESULTS: Exhaustive exercise did not (or hardly) affect cycle rate
      and choice of technique. The physiological response was most prominent in slight
      incline-high speed conditions, independent of exercise duration. Exhaustive
      exercise affected the physiological response in a differentiated manner. HR and
      RER remained, respectively, higher and lower after fatigue, while [Formula: see
      text] (and thereby GE) were affected only during approximately the first 8 min of
      post-exhaustion exercise. CONCLUSIONS: Exhaustive exercise has a minimal effect
      on choice of technique in classic cross-country skiing with free choice of sub
      technique, even though physiological stress is increased.

PMID- 30105642
TI  - Induced Expression of Endogenous CXCR4 in iPSCs by Targeted CpG Demethylation
      Enhances Cell Migration Toward the Ligand CXCL12.
AB  - Poor homing of cells after transplantation is an unresolved common issue in
      cardiac cell therapies. To enhance stem cell homing, the ligand CXC motif
      chemokine 12 (CXCL12) and its specific receptor CXC receptor type 4 (CXCR4) have
      been employed as a system in this study to show that induced expression of the
      endogenous CXCR4 gene in mouse-induced pluripotent stem cells (iPSCs) improved
      the cell migration. Loci-specific epigenome editing in the form of CpG
      demethylation at CXCR4 promoter region of the mouse iPSCs was accomplished with
      CXCR4b-TAL-Tet1c, chimeric fusion proteins of the catalytic domain of ten-eleven
      translocation 1 (TET1) to the C-terminal end of the DNA binding domains of
      predesigned synthetic transcription activator-like effectors (TALEs) that
      recognize specific DNA sequences within the mouse CXCR4 promoter region.
      Infection of the mouse iPSCs with the engineered CXCR4b-TAL-Tet1c in the form of
      lentiviral particles induced the loci-specific CpG demethylation and subsequent
      activation of CXCR4 expression in mouse iPSCs. As expected, the CXCR4
      overexpressing iPSCs exhibited 3.9-fold greater migration than the control iPSCs
      did without alteration of the stemness and activated phosphorylation of AKT
      significantly. These results set a sound foundation for subsequent in vivo iPSCs
      transplantation studies in rodent models of acute myocardial infarction and heart
      failure. We show that TALEs can enhance the expression of CXCR4 by CpG
      methylation, and may retain the stemness. Migration of iPSCs activated by CXCL12
      is associated with significant phosphorylation of AKT, not ERK1/2.

PMID- 30105641
TI  - Characterization of the retina-induced relaxation in mice.
AB  - PURPOSE: The retinal relaxing factor (RRF) is a continuously released factor from
      the retina that causes vasorelaxation, the identity and potential role in
      physiology of which remain largely unknown. Experiments were performed to find
      out whether the RRF-induced relaxation is influenced by serotonin, glutamate, L
      cysteine, the cytochrome P450 pathway, the cyclooxygenase pathway, or oxidative
      stress. In addition, the sensitivity of retinal and non-retinal arteries towards
      the RRF was compared. METHODS: In vitro tension measurements were performed on
      isolated mouse femoral or bovine retinal arteries to study the vasorelaxing
      effect of the RRF, induced by mouse or bovine retinas. RESULTS: The presence of
      serotonin, glutamate, or L-cysteine did not alter the RRF-induced relaxation.
      Increasing oxidative stress by hydroquinone and diethyldithiocarbamic acid sodium
      salt enhanced the RRF response. Inhibition of the cytochrome P450 or the
      cyclooxygenase pathway did not cause any alteration. Surprisingly, the RRF
      induced relaxation was enhanced by the presence of flufenamic acid or
      carbenoxolone. Furthermore, bringing retinal tissue in close contact with retinal
      or non-retinal arteries induced comparable relaxations. CONCLUSIONS: Serotonin,
      glutamate, L-cysteine, the cytochrome P450, and the cyclooxygenase pathway do not
      influence the RRF-induced relaxation and the RRF-induced relaxation seems to be
      resistant to oxidative stress. The mechanism responsible for the enhanced RRF
      induced relaxation in the presence of flufenamic acid or carbenoxolone remains
      elusive and the RRF does not show more effectivity on retinal arteries.

PMID- 30105643
TI  - Role of Chemical Mediators in Aquatic Interactions across the Prokaryote
      Eukaryote Boundary.
AB  - There is worldwide growing interest in the occurrence and diversity of
      metabolites used as chemical mediators in cross-kingdom interactions within
      aquatic systems. Bacteria produce metabolites to protect and influence the growth
      and life cycle of their eukaryotic hosts. In turn, the host provides a nutrient
      enriched environment for the bacteria. Here, we discuss the role of waterborne
      chemical mediators that are responsible for such interactions in aquatic multi
      partner systems, including algae or invertebrates and their associated bacteria.
      In particular, this review highlights recent advances in the chemical ecology of
      aquatic systems that support the overall ecological significance of signaling
      molecules across the prokaryote-eukaryote boundary (cross-kingdom interactions)
      for growth, development and morphogenesis of the host. We emphasize the value of
      establishing well-characterized model systems that provide the basis for the
      development of ecological principles that represent the natural lifestyle and
      dynamics of aquatic microbial communities and enable a better understanding of
      the consequences of environmental change and the most effective means of managing
      community interactions.

PMID- 30105644
TI  - Association Between Objectively Measured Physical Activity and Opioid, Hypnotic,
      or Anticholinergic Medication Use in Older People: Data from the Physical
      Activity Cohort Scotland Study.
AB  - BACKGROUND: Centrally acting medications cause cognitive slowing and
      incoordination, which could reduce older people's physical activity levels. This
      association has not been studied previously. OBJECTIVES: The aim of this study
      was to examine the association between opioid, hypnotic and anticholinergic
      medication, and objectively measured physical activity, in a cohort of older
      people. METHODS: We used data from the Physical Activity Cohort Scotland, a
      representative cohort of community-dwelling older people aged 65 years and over
      who were assessed at baseline and again 2-3 years later. Objective physical
      activity was measured using Stayhealthy RT3 accelerometers over 7 days. Baseline
      medication use (opioid use, hypnotic use, modified Anticholinergic Risk Scale
      [mARS]) was obtained from linked, routinely collected community prescribing
      records. Cross-sectional and longitudinal associations between baseline
      medication use and both baseline activity and change in activity over time were
      analysed using unadjusted and adjusted linear regression models. RESULTS:
      Overall, 310 participants were included in the analysis; mean age 77 years
      (standard deviation 7). No association was seen between baseline use of any
      medication class and baseline physical activity levels in unadjusted or adjusted
      models. For change in activity over time, there was no difference between users
      and non-users of hypnotics or opioids. Higher anticholinergic burden was
      associated with a steeper decline in activity over the follow-up period (mARS 0: 
      7051 counts/24 h/year; mARS 1-2: - 15,942 counts/24 h/year; mARS >= 3: - 19,544
      counts/24 h/year; p = 0.03) and this remained robust to multiple adjustments.
      CONCLUSION: Anticholinergic burden is associated with greater decline in
      objectively measured physical activity over time in older people, a finding not
      seen with hypnotic or opioid use.

PMID- 30105646
TI  - Rats can replay episodic memories of past odors.
AB  - Panoz-Brown et al. (Current Biology, 28, 1628-1634, 2018) present evidence to
      support the hypothesis that rats can replay their episode memory to determine
      which of a series of odors was at a particular location in the sequence. They
      also show that the hippocampus is likely involved in allowing the rats to replay
      those memories.

PMID- 30105645
TI  - The Role of Targeted Agents and Immunotherapy in Older Patients with Non-small
      Cell Lung Cancer.
AB  - Lung cancer is predominantly a disease of the elderly. This subgroup of patients
      poses many challenges and an appropriate geriatric assessment is crucial for
      treatment personalisation in order to reduce the risk of over- or under
      treatment. Whilst cytotoxic chemotherapy has been the backbone of advanced non
      small cell lung cancer (NSCLC) treatment for decades, the development of targeted
      agents for driver mutations such as EGFR, ALK, BRAF and ROS1 has changed the
      treatment paradigm and natural history of this disease. More recently, the
      development of immune checkpoint inhibitors has revolutionised treatment for a
      larger group of patients with locally advanced/metastatic disease. Limited data
      exist on safety and efficacy of these agents in the elderly population. Many
      questions remain regarding the available evidence for targeted therapies and
      immune checkpoint blockade in NSCLC and, in particular, their role in this
      subgroup of patients.

PMID- 30105648
TI  - Prenatal Exposure to an Acute Stressor and Children's Cognitive Outcomes.
AB  - Exposure to environmental stressors is highly prevalent and unequally distributed
      along socioeconomic lines and may have enduring negative consequences, even when
      experienced before birth. Yet, estimating the consequences of prenatal stress on
      children's outcomes is complicated by the issue of confounding (i.e., unobserved
      factors correlated with stress exposure and with children's outcomes). I combine
      a natural experiment-a strong earthquake in Chile-with a panel survey to capture
      the effect of prenatal exposure on acute stress and children's cognitive ability.
      I find that stress exposure in early pregnancy has no effect on children's
      cognition among middle-class families, but it has a strong negative influence
      among disadvantaged families. I then examine possible pathways accounting for the
      socioeconomic stratification in the effect of stress, including differential
      exposure across socioeconomic status, differential sensitivity, and parental
      responses. Findings suggest that the interaction between prenatal exposures and
      socioeconomic advantage provides a powerful mechanism for the intergenerational
      transmission of disadvantage.

PMID- 30105647
TI  - Inequity aversion in dogs: a review.
AB  - The study of inequity aversion in animals debuted with a report of the behaviour
      in capuchin monkeys (Cebus apella). This report generated many debates following
      a number of criticisms. Ultimately, however, the finding stimulated widespread
      interest, and multiple studies have since attempted to demonstrate inequity
      aversion in various other non-human animal species, with many positive results in
      addition to many studies in which no response to inequity was found. Domestic
      dogs represent an interesting case as, unlike many primates, they do not respond
      negatively to inequity in reward quality but do, however, respond negatively to
      being unrewarded in the presence of a rewarded partner. Numerous studies have
      been published on inequity aversion in dogs in recent years. Combining three
      tasks and seven peer-reviewed publications, over 140 individual dogs have been
      tested in inequity experiments. Consequently, dogs are one of the best studied
      species in this field and could offer insights into inequity aversion in other
      non-human animal species. In this review, we summarise and critically evaluate
      the current evidence for inequity aversion in dogs. Additionally, we provide a
      comprehensive discussion of two understudied aspects of inequity aversion, the
      underlying mechanisms and the ultimate function, drawing on the latest findings
      on these topics in dogs while also placing these developments in the context of
      what is known, or thought to be the case, in other non-human animal species.
      Finally, we highlight gaps in our understanding of inequity aversion in dogs and
      thereby identify potential avenues for future research in this area.

PMID- 30105652
TI  - Moral People or Moral Projects? Worker Altruism in Youth Residential Treatment.
AB  - Paraprofessional youth care workers in residential treatment centers (RTCs) are
      responsible for the everyday care, supervision, and treatment of youth with
      serious behavioral and mental health challenges. Turnover rates among this poorly
      paid workforce are high, and it is not known why individuals seek and maintain
      youth care work despite its significant challenges. Following anthropologists who
      study morality as situated practice, we investigate the role of altruism in
      recruiting and retaining workers in RTCs. We ask: How do managers and youth care
      workers understand altruism and its role in youth care work and what are the
      consequences of those understandings? Through organizational ethnography of an
      RTC, we show that workers and management understood altruism differently.
      Managers viewed altruism as an inherent trait of some and attributed turnover to
      its lack. Although workers sometimes enacted this script, they understood
      themselves as engaged in far more complex situated moral projects in which
      altruism was only one part. We demonstrate political effects of these differing
      understandings of altruism, namely, that management deflected institutional
      critique by viewing it as a sign of workers' immorality. We offer modest
      recommendations for RTCs seeking to recruit and retain competent youth care
      workers and address potential new directions for moral anthropology of
      organizations.

PMID- 30105653
TI  - Measuring and Understanding Depression in Women in Kisoro, Uganda.
AB  - Depression is highly prevalent and the cause of considerable suffering for
      peoples across the globe. Case finding for depression is challenging because
      individuals often do not recognize the symptoms in themselves or may resist the
      diagnosis as a result of cultural stigma. Screening instruments, to be accurate,
      must be valid in the particular setting in which they are being applied, and
      diagnosis in primary care settings, is further made challenging because patients
      often present with a wide variety of somatic symptoms that could be medical. 115
      women were screened for depression in this study in one community in Uganda, and
      87 were found to be depressed using the SRQ-20. The cognitive impairment and
      decreased energy sub-scales of the SRQ-20 seemed to best differentiate for
      depression. We then interviewed the 87 women and found that, overwhelmingly,
      their complaints were somatic, and that their expectation for treatment was to
      receive medical tests and medications. Caregivers in primary care clinics in
      Uganda should know that in the reporting of their somatic symptoms patients may
      be trying to communicate more about themselves than just the state of their
      physical health; and that feelings of uselessness or of hopelessness when
      expressed by a patient should lead them to suspect severe mental illness since
      these symptoms were not found to be characteristic of the milder depression that
      is highly prevalent in Ugandan women.

PMID- 30105649
TI  - Degradation and detoxification of azo dyes by a salt-tolerant yeast Cyberlindnera
      samutprakarnensis S4 under high-salt conditions.
AB  - A new yeast strain which was capable of degrading various azo dyes under high
      salt conditions was identified in this study. The results showed that the yeast
      named S4 was identified as Cyberlindnera samutprakarnensis through 26S rDNA
      sequence analysis and could decolorize more than 97% of Acid Red B (ARB) within
      18 h under the optimal conditions. The acute toxicity of ARB sharply decreased
      after degradation. NADH-DCIP reductase and lignin peroxidase were determined as
      the key reductase and oxidase of the yeast S4, respectively. Furthermore, it was
      proposed that ARB was degraded by strain S4 successively through reduction of azo
      bonds, hydroxylation, deamination, desulfonation and finally to the TCA cycle.

PMID- 30105654
TI  - Narrative Navigation: HIV and (Good) Care in Aceh, Indonesia.
AB  - In this article, I elaborate the concept of narrative navigation to analyze the
      subjective and intersubjective ways in which people struggle through experiences
      of illness by constructing multiple, ambiguous and non-linear narratives that may
      continuously change, as they reposition themselves within changing circumstances.
      Drawing on ethnographic material on HIV care in Aceh, Indonesia, I show how
      subjunctivity and open-endedness are crucial narrative ways in which people
      living with HIV, their relatives, medical doctors and support group workers
      adjust to possibilities and limitations of care over time, thereby continuously
      negotiating what good care may be. Unfolding within a changing Indonesian
      healthcare system, their narrative navigations reveal caregiving to be a complex
      and contradictory process, thereby problematizing boundaries between good care
      and neglect.

PMID- 30105650
TI  - Neuroprotective Effect of Hydrogen Sulfide in Hyperhomocysteinemia Is Mediated
      Through Antioxidant Action Involving Nrf2.
AB  - Homocysteine (Hcy) is a sulfur-containing amino acid derived from methionine
      metabolism. Elevated plasma Hcy levels (> 15 uM) result in a condition called
      hyperhomocysteinemia (HHcy), which is an independent risk factor in the
      development of various neurodegenerative disorders. Reactive oxygen species (ROS)
      produced by auto-oxidation of Hcy have been implicated in HHcy-associated
      neurological conditions. Hydrogen sulfide (H2S) is emerging as a potent
      neuroprotective and neuromodulator molecule. The present study was aimed to
      evaluate the ability of NaHS (a source of H2S) to attenuate Hcy-induced oxidative
      stress and altered antioxidant status in animals subjected to HHcy. Impaired
      cognitive functions assessed by Y-maze and elevated plus maze in Hcy-treated
      animals were reversed on NaHS administration. Increased levels of ROS, lipid
      peroxidation, protein carbonyls, and 4-hydroxynonenal (4-HNE)-modified proteins
      were observed in the cortex and hippocampus of Hcy-treated animals suggesting
      accentuated oxidative stress. This increase in Hcy-induced oxidative stress was
      reversed following NaHS supplementation. GSH/GSSG ratio, activity of antioxidant
      enzymes viz; superoxide dismutase, glutathione peroxidase, glutathione reductase,
      and glutathione-S-transferase were decreased in Hcy-treated animals. NaHS
      supplementation, on the otherhand, restored redox ratio and activity of
      antioxidant enzymes in the brains of animals with HHcy. Further, NaHS
      administration normalized nuclear factor erythroid 2-related factor 2 expression
      and acetylcholinesterase (AChE) activity in the brain of Hcy-treated animals.
      Histopathological studies using cresyl violet indicated higher number of pyknotic
      neurons in the cortex and hippocampus of HHcy animals, which were reversed by
      NaHS administration. The results clearly demonstrate that NaHS treatment
      significantly ameliorates Hcy-induced cognitive impairment by attenuating
      oxidative stress, improving antioxidant status, and modulating AChE activity
      thereby suggesting potential of H2S as a therapeutic molecule.

PMID- 30105655
TI  - Treatment and Monitoring Patterns Among Premenopausal Women with HR+/HER2-
      Advanced Breast Cancer.
AB  - INTRODUCTION: Premenopausal women with hormone receptor positive (HR+) and human
      epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (aBC)
      often present with aggressive tumor types that lead to poor prognosis, high rates
      of recurrence, and mortality. Although clinical guidelines provide evidence-based
      recommendations for optimal treatment and monitoring, there is a dearth of
      information regarding treatment and monitoring patterns in clinical practice. In
      this study, we describe treatment and monitoring patterns among premenopausal
      women with HR+/HER2- aBC in real-world practice. METHODS: A large US claims
      database was used to describe treatment patterns for patients in first, second,
      and third lines of therapy. Treatment monitoring included complete blood count
      (CBC), liver function test (LFT), and electrocardiogram (EKG) monitoring,
      described for the first three lines of therapy, and separately for patients
      receiving endocrine monotherapy (ET) and chemotherapy. RESULTS: Among 3203
      patients, chemotherapy was the most common treatment used in first-line (63.6%)
      and second-line therapy (66.9%). ET was used in 34.4, 30.1, and 73.6% of patients
      in first, second, and third lines of therapy, respectively. The two most common
      treatment sequences were a single line of ET (27.3%), and two consecutive lines
      of chemotherapy followed by a line of ET (19.3%). Patients receiving chemotherapy
      were monitored with CBC on average more than two times per month, and for LFT one
      to two times per month. Patients receiving ET were monitored with CBC and LFT on
      average once every 2-3 months. Overall, approximately 20% of patients were
      monitored with an EKG at some point during each line of therapy. CONCLUSION: A
      considerable proportion of premenopausal women with aBC received first- and
      second-line chemotherapy, which appears inconsistent with current clinical
      guidelines. The observed treatment heterogeneity points to a lack real-world
      consensus on the management of premenopausal women with HR+/HER2- aBC. FUNDING:
      Novartis Pharmaceuticals Corporation.

PMID- 30105658
TI  - Evaluating the Impact and Benefits of Fluticasone Furoate/Vilanterol in
      Individuals with Asthma or COPD: A Mixed-Methods Analysis of Patient Experiences.
AB  - INTRODUCTION: This study evaluated patients' experiences with fluticasone
      furoate/vilanterol (FF/VI) combination therapy in UK patients with asthma or
      chronic obstructive pulmonary disease (COPD). METHODS: Participants aged >= 18
      years, with self-reported, physician-diagnosed asthma or COPD (>= 1 year) who had
      been receiving FF/VI (>= 3 months) were recruited from UK primary care. This two
      phase, mixed-methods study consisted of a semi-structured, telephone-interview
      phase (qualitative) and a self-completed online/paper-survey phase
      (quantitative). RESULTS: The telephone-interview phase included 50 individuals
      [asthma, n = 25; COPD, n = 25; mean age (SD) 56.7 years (13.3); 50% female]. Of
      these, 21 with asthma reported that their condition was stable/well controlled
      and 13 with COPD felt their condition was manageable. Most participants found
      FF/VI easy to use (asthma, 25; COPD, 23), easy to integrate into their daily
      routine (asthma, 25; COPD, 24), and able to control symptoms for >= 24 h (asthma,
      14; COPD, 16). During the survey phase, 199 individuals were recruited [asthma, n
      = 100; COPD, n = 99; mean age (SD) 63.6 years (15.1); 59.3% female]. Most
      participants were satisfied/very satisfied with the efficacy of FF/VI in terms of
      all-day symptom relief (asthma, 84%; COPD, 75%) and found FF/VI easy/very easy to
      fit into their daily routine (asthma, 99%; COPD, 96%), easy/very easy to use
      (asthma, 97%; COPD, 92%), and convenient/very convenient to take as instructed
      (asthma, 95%; COPD, 93%). Significantly more individuals with asthma (87% versus
      46%, P < 0.001) and numerically more individuals with COPD (84% versus 76%, P =
      0.055) were satisfied/very satisfied with FF/VI compared with their most recent
      previous maintenance medication. CONCLUSION: The majority of individuals in this
      study had confidence in FF/VI and were satisfied or very satisfied with various
      key attributes of the treatment. TRIAL REGISTRATION: GSK study HO-15
      15503/204888. FUNDING: GSK.

PMID- 30105659
TI  - Tailored Healthcare: Two Perspectives on the Development and Use of Patient
      Profiles.
AB  - : Calls for a more tailored approach to the management of cardiometabolic and
      musculoskeletal diseases have been increasing. Although tailored care is a
      centuries-old concept, it is still unclear how it should be best practised. The
      current paper introduces two phenotype-based Dutch approaches to support tailored
      care. One approach focuses on patients with type 2 diabetes, the other on
      patients undergoing total joint replacement. Using the patient profiling
      approach, both projects propose that care can be tailored by the assessment of
      biopsychosocial patient characteristics, stratification of patients into
      subgroups of patients with similar care needs, abilities, and preferences (so
      called patient profiles) and tailoring of care in concordance with the common
      care preferences of these profiles. In this article, the advantages and
      disadvantages of the method are discussed to enable researchers or clinicians who
      want to extend the patient profiling approach to other patient populations to
      carefully evaluate these in relation to their project's focus and available
      resources. FUNDING: Novo Nordisk B.V., the Netherlands Organisation for
      Scientific Research (NWO) (Grant 314-99-118) and Zimmer Biomet Inc.

PMID- 30105657
TI  - Effectiveness and Tolerability of Micafungin in Chinese Patients with Invasive
      Fungal Infections: A Retrospective, Multicenter Study.
AB  - INTRODUCTION: Invasive fungal infections (IFIs) are a significant health problem
      in immunocompromised patients, resulting in substantial morbidity, mortality, and
      healthcare costs. Micafungin is a broad-spectrum echinocandin with activity
      against Candida and Aspergillus spp. This was a multicenter, non-comparative,
      retrospective observational study that evaluated the effectiveness and
      tolerability of intravenously administered micafungin for treating IFIs caused by
      Candida and Aspergillus spp. METHODS: Adult patients in China who had received at
      least one dose of intravenously administered micafungin were eligible.
      Retrospective data (May 2008-April 2015) were extracted from patients' medical
      files and recorded using electronic data capture. The primary endpoint was
      overall success rate (patients with complete or partial response). Subgroup
      analyses determined effectiveness according to diagnostic certainty, fungal
      species, type of IFI, duration of micafungin treatment, and daily dose of
      micafungin. Tolerability, including the incidence of adverse events (AEs), was
      also assessed. RESULTS: Overall, 2555 patients who received at least one dose of
      micafungin were identified. The mean duration of treatment and mean daily dose
      were 10.2 days and 133.0 mg, respectively. The overall success rate was 60.8%;
      this was significantly higher in patients who received treatment for at least 1
      week (range 67.9-71.6% [mean 69.2%]) compared with less than 1 week (47.8%; P <
      0.0001), and those who received 50-100 mg (65.7%) compared with other daily doses
      (range 42.9-60.1% [mean 59.0%]; P = 0.0011). Success rates in Candida- and
      Aspergillus-infected patients were similar (61.9% and 56.8%, respectively). AEs
      and adverse drug reactions were observed in 36.2% and 4.5% of patients,
      respectively. The majority of AEs were mild, while discontinuation due to AEs was
      low (2.3%). CONCLUSION: Micafungin is effective and well tolerated for the
      treatment of patients with IFIs in China, as demonstrated in Candida- and
      Aspergillus-infected adults. Subgroup analyses highlighted the potential benefits
      of treating IFIs with micafungin for a minimum of 1 week. TRIAL REGISTRATION:
      ClinicalTrials.gov identifier NCT02678598. FUNDING: Astellas Pharma Inc.

PMID- 30105662
TI  - Yet Another Mortality with a Biliopancreatic Limb of > 200 cm with One
      Anastomosis Gastric Bypass.

PMID- 30105663
TI  - Letter to the Editor in Response to "Elipse Balloon: the Pitfalls of Excessive
      Simplicity" by Angrisani, L., Santonicola, A., Vitiello, A. et al. OBES SURG
      (2018) 28: 1419.

PMID- 30105660
TI  - Small Intestinal Length Associates with Serum Triglycerides Before and After
      LRYGB.
AB  - BACKGROUND AND AIMS: Different bariatric procedures have been associated with
      variable weight loss and decrease in serum levels of lipids and lipoproteins.
      This variation could be partly related to the length of the small intestinal
      bypass. We evaluated the association of the small intestinal length with the non
      alcoholic fatty liver disease (NAFLD) at baseline and with lipid metabolism
      before and after laparoscopic Roux-en-Y gastric bypass (LRYGB). METHODS: Seventy
      consecutive morbidly obese patients were recruited to this prospective study. A
      standard 60-cm biliopancreatic limb (BPL) and 120-cm alimentary limb (AL) was
      performed, and thereafter, the common channel (CC) length was measured during
      elective LRYGB. Histological analysis of liver biopsy to diagnose NAFLD was
      performed. The mRNA expression of genes participating in the cholesterol and
      fatty acid metabolism in the liver was analyzed. RESULTS: Female sex (p = 0.006),
      serum triglycerides (TG, p = 0.016), serum alanine aminotransferase (ALT, p =
      0.007), and liver steatosis (p = 0.001) associated with the small intestinal
      length (BPL + AL + CC) at baseline. Association remained significant between
      levels of serum TG and CC length (p = 0.048) at 1-year follow-up. Liver mRNA
      expression of genes regulating cholesterol synthesis and bile metabolism did not
      associate with the baseline small intestinal length. CONCLUSIONS: Our findings
      support the suggestions that small intestinal length regulates TG metabolism
      before and after LRYGB. Therefore, modification of the length of bypassed small
      intestine based on measured total small intestinal length could optimize the
      outcomes of the elective LRYGB.

PMID- 30105661
TI  - Psychological and Behavioral Aspects of Primary and Reoperative Surgery: a 6
      Month Longitudinal Study.
AB  - BACKGROUND: Problematic eating behaviors and general psychopathology have been
      associated with poor weight loss after bariatric surgery. However, little is
      known about how these aspects impact weight loss outcomes for the increasing
      number of patients undergoing reoperative surgeries. This study compares
      disordered eating and weight-related outcomes before and 6 months after surgery
      in patients undergoing primary (P-Group) and reoperative bariatric surgery (R
      Group). METHODS: This longitudinal study assessed 122 P-Group and 116 R-Group
      patients before and 6 months after surgery. The assessment included the eating
      disorder examination diagnostic items, and a set of self-report measures
      assessing eating disorder symptomatology, grazing, depression, anxiety, and
      negative urgency. RESULTS: Preoperatively, no differences were found between the
      R- and P-Groups in terms of disordered eating-related variables (except for shape
      concern, which was higher for the R-Group). At 6 months after surgery, the R
      Group revealed significantly higher values for restraint (F(1,219) = 5.84, p =
      0.016), shape (F(1,219) = 5.59, p = 0.019), weight concerns (F(1,219) = 13.36, p
      = 0.000), depression (F(1,219) = 7.17, p = 0.008), anxiety (F(1,219) = 6.94, p = 
      0.009), and compulsive grazing (F(1,219) = 6.13, p = 0.014). No significant pre-
      or post-surgery predictors of weight loss were found for the P-Group (chi2 =
      0.70, p = 0.872). In the R-Group, post-surgery anxiety (Waldchi2(1) = 6.19, p =
      0.01) and the post-surgery number of days with grazing in the previous month
      (Waldchi2(1) = 3.90, p = 0.04) were significant predictors of weight loss.
      CONCLUSION: At 6 months after surgery, the R-Group presented more problematic
      eating and general psychological distress, which may put these patients at
      greater risk of poorer long-term weight outcomes.

PMID- 30105664
TI  - Increase in Physical Activity After Bariatric Surgery Demonstrates Improvement in
      Weight Loss and Cardiorespiratory Fitness.
AB  - BACKGROUND: Low cardiorespiratory fitness is strongly associated with
      cardiovascular diseases and mortality. Although increased physical activity can
      improve cardiorespiratory fitness, this relationship has not been examined in a
      large bariatric population undergoing perioperative care focusing on long-term
      lifestyle change. OBJECTIVES: To evaluate changes in physical activity, weight
      loss, and cardiorespiratory fitness up to 24 months after bariatric surgery, and
      to evaluate the relationships of change in physical activity with weight loss and
      change in cardiorespiratory fitness. MATERIALS AND METHODS: Four thousand seven
      hundred eighty-five patients who underwent primary Roux-en-Y gastric bypass or
      sleeve gastrectomy between January 2012 and December 2014 were included. Physical
      activity was assessed by the Baecke questionnaire (work, leisure, and sport
      activity) and cardiorespiratory fitness, defined as VO2max relative to fat-free
      mass (VO2max/FFM), was assessed by the Astrand test. RESULTS: Twenty-four months
      postoperative, significant improvements were seen in sport and leisure activity
      assessments (n = 3548, P < 0.001), weight loss (n = 3695, P < 0.001), and
      VO2max/FFM (n = 1852, P < 0.001). Furthermore, regression analysis showed that
      change in leisure activity was positively associated with weight loss (n = 3535,
      beta = 1.352, P < 0.001) and change in sport activity was positively associated
      with change in VO2max/FFM (n = 1743, beta = 1.730, P < 0.001). CONCLUSION:
      Bariatric surgery complemented by a comprehensive bariatric care program can lead
      to improvement in physical activity, as well as weight loss and improvement in
      cardiorespiratory fitness. The positive associations of change in leisure
      activity with weight loss and change in sport activity with cardiorespiratory
      fitness suggest that bariatric care programs can enhance postoperative outcomes
      by improving the patient's physical activity.

PMID- 30105665
TI  - Which factors can aid clinicians to identify a risk of pain during the following
      month in patients with bone metastases? A longitudinal analyses.
AB  - PURPOSE: Explore clinical factors associated with higher pain intensity and
      future pain in patients with bone metastases to identify patients who can benefit
      from closer follow-up or pain-modifying interventions. METHODS: This is a
      secondary analysis of 606 patients with bone metastases included in a multicenter
      longitudinal study. The dependent variables were "average pain" and "worst pain"
      in the last 24 h (0-10 NRS). Twenty independent variables with potential
      association to pain intensity were selected based on previous literature. Cross
      sectional analyses were performed with multiple linear regression to explore
      factors associated with pain intensity at baseline. Longitudinal data were
      analyzed with a generalized equation models to explore current factors associated
      with pain intensity at the next visit in 1 month. RESULTS: Current pain intensity
      (p < 0.001), sleep disturbances (p 0.01 and 0.006), drowsiness (p 0.003 and
      0.033) and male gender (p 0.045 and 0.001) were associated with higher average
      and worst pain intensity in 1 month. In addition, breakthrough pain was related
      to higher worst pain intensity (p 0.003) in 1 month. The same variables were also
      associated with higher average pain intensity at baseline. CONCLUSION: Higher
      current pain intensity, sleep disturbances, drowsiness, male gender, and
      breakthrough pain are factors associated with higher pain intensity in patients
      with bone metastases at the next follow-up in 1 month. These factors should be
      assessed in clinical practice and may aid clinicians in identifying patients that
      can benefit from closer follow-up or interventions to prevent lack of future pain
      control. TRIAL REGISTRATION IN CLINICALTRIALS.GOV : NCT01362816.

PMID- 30105666
TI  - Risk factors and prediction model for persistent breast-cancer-related
      lymphedema: a 5-year cohort study.
AB  - PURPOSE: Breast-cancer-related lymphedema (BCRL) can be a transient or persistent
      condition. The aims of this study were to (1) identify and weigh the risk factors
      for persistent lymphedema (PLE) among all patients with BCRL and (2) establish a
      prediction model for the occurrence of PLE. METHODS: A cohort of 342 patients
      with BCRL with a median follow-up of 5 years after the onset of swelling was
      analyzed. PLE was defined as a hardening of the subcutaneous tissue, the
      persistence of the circumferential difference (CD) between arms, or a flare-up of
      swelling during follow-up. Multiple logistic regression was used to identify risk
      factors for PLE, including tumors, treatments, and patient-related factors. The
      prediction accuracy of the model was assessed using the area under the receiver
      operating characteristic curve (AUC). RESULTS: Of the 342 patients with BCRL, 229
      (67%) had PLE. Multiple logistic regression analysis revealed that the number of
      lymph node metastases (p = 0.012), the maximal CD between arms at the first
      occurrence of swelling (p < 0.001), and the largest difference during follow-up
      (p < 0.001) were significant predictors for PLE. The corresponding AUC was 0.908.
      Although inclusion of body weight gains (p = 0.008) and maximal CD at the latest
      follow-up (p = 0.002) increased the analytical accuracy (AUC = 0.920), the
      resulting AUC values (p = 0.113) were not significantly different. CONCLUSIONS:
      BCRL is persistent in two thirds of patients. Patients with more lymph node
      metastases, weight gain, and larger CD since the onset of swelling and during
      follow-up have an increased likelihood of developing PLE.

PMID- 30105667
TI  - Using paracrine effects of Ad-MSCs on keratinocyte cultivation and fabrication of
      epidermal sheets for improving clinical applications.
AB  - Recent advances in wound healing have made cell therapy a potential approach for
      the treatment of various types of skin defects such as trauma, burns, scars and
      diabetic leg ulcers. Cultured keratinocytes have been applied to burn patients
      since 1981. Patients with acute and chronic wounds can be treated with
      autologous/allograft cultured keratinocytes. There are various methods for
      cultivation of epidermal keratinocytes used in cell therapy. One of the important
      properties of an efficient cell therapy is the preservation of epidermal stem
      cells. Mesenchymal Stem Cells (MSCs) are major regulatory cells involved in the
      acceleration of wound healing via induction of cell proliferation, angiogenesis
      and stimulating the release of paracrine signaling molecules. Considering the
      beneficial effects of MSCs on wound healing, the main aim of the present study is
      investigating paracrine effects of Adipose-derived Mesenchymal Stem Cell (Ad
      MSCs) on cultivation of keratinocytes with focusing on preservation of stem cells
      and their differentiation process. We further introduced a new approach for
      culturing isolated keratinocytes in vitro in order to generate epidermal
      keratinocyte sheets without using a feeder layer. To do so, Ad-MSC conditioned
      medium was applied as an alternative to commercial media for keratinocyte
      cultivation. In this study, the expression of several stem/progenitor cell (P63,
      K19 and K14) and differentition (K10, IVL and FLG) markers was examined using
      real time PCR on days 7, 14 and 21 of culture in keratinocytes in Ad-MSC
      conditioned medium. P63 and alpha6 integrin expression was also evaluated via
      flow cytometry. The results were compared with control group including
      keratinocytes cultured in EpiLife medium and our data indicated that this Ad-MSC
      conditioned medium is a good alternative for keratinocyte cultivation and
      producing epidermal sheets for therapeutic and clinical purposes. The reasons are
      the expression of stem cell and differentiation markers and overcoming the
      requirement for feeder layer which leads to a xenograft-free transplantation.
      Besides, this approach has low cost and is easier to perform. However, more in
      vitro and in vivo experiments as well as safety evaluation required before
      clinical applications.

PMID- 30105656
TI  - Anti-Anginal Effectiveness and Tolerability of Trimetazidine Modified Release 80
      Mg Once Daily in Stable Angina Patients in Real-World Practice.
AB  - INTRODUCTION: Trimetazidine (TMZ) was shown to reduce angina symptoms and
      increase the exercise capacity in stable angina (SA) patients. A new formulation
      allowing a once-daily (od) dosage could improve patients' satisfaction and
      adherence. METHODS: ODA was a 3-month, observational, multicenter, prospective
      Russian study in SA patients with persistent symptoms despite therapy. Angina
      attack frequency, short-acting nitrate (SAN) consumption, adherence to
      antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od
      were assessed in a real-world setting. RESULTS: A total of 3066 patients were
      included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to
      a significant (p < 0.001) decrease in angina attack frequency (from 4.7 +/- 3.5
      to 0.9 +/- 1.3/week) and SAN use (from 4.5 +/- 3.9 to 0.7 +/- 1.3/week). Overall
      tolerability and effectiveness were rated as "very good" by the majority of
      physicians. Medication adherence improved significantly, with good adherence
      reported by 56% of patients (vs. 24% at baseline, p < 0.0001) and non-adherence
      by 3% (vs. 36% at baseline, p < 0.0001) at month 3. Patient satisfaction with TMZ
      od was 9.5 [on a scale of 1 to 10 (very satisfied)]. Patients reported improved
      physical activity: more patients reported no limitations (15% vs. 1% at baseline
      p < 0.01), slight limitation (46% vs. 5% at baseline, p < 0.001) or moderate
      limitation (30% vs. 23%, p < 0.01) and fewer patients reported substantial
      limitation (8% vs. 52% at baseline, p < 0.001) or very marked reduction (1% vs.
      19% at baseline, p < 0.01) at month 3. CONCLUSION: In this prospective,
      observational study, TMZ 80 mg od effectively reduced angina attacks and SAN
      consumption, improved physical activity and adherence and was well tolerated in
      chronic SA patients. TRIAL REGISTRATION: ISRCTN registry Identifier,
      ISRCTN97780949. FUNDING: Servier. Plain language summary available for this
      article.

PMID- 30105668
TI  - Phase 1 dose-escalation study of momelotinib, a Janus kinase 1/2 inhibitor,
      combined with gemcitabine and nab-paclitaxel in patients with previously
      untreated metastatic pancreatic ductal adenocarcinoma.
AB  - Purpose Preclinical evidence suggests the importance of Janus activating kinase
      (JAK) and TANK-binding kinase 1 (TBK1) in pancreatic ductal adenocarcinoma
      (PDAC). We evaluated the safety and efficacy of momelotinib (MMB), a JAK1/2
      inhibitor with additional activity against TBK1, plus albumin-bound paclitaxel +
      gemcitabine (nab-P + G), in patients with previously untreated metastatic PDAC.
      Experimental Design Patients were enrolled into five cohorts of increasing doses
      of MMB between 100 and 200 mg administered once or twice daily in combination
      with nab-P + G in 28-day cycles to determine maximum tolerated dose (MTD).
      Safety, efficacy, pharmacokinetics, and pharmacodynamics were assessed for all
      patients. Results Twenty-five patients were enrolled. Dose-limiting toxicities of
      Grade 3 diarrhea occurred in 1 patient each in the 100 and 200 mg MMB once-daily
      dose groups. MTD was not reached. The 200 mg MMB twice-daily was the maximum
      administered dose. Objective response rate was 28% (all partial responses), and
      13 (52%) patients had a best response of stable disease. The most common adverse
      events (AEs) were fatigue (80%), nausea (76%), and anemia (68%). Grade 3 or 4
      AEs, most commonly neutropenia (32%), were reported by 88% of patients, of which
      44% were considered related to MMB. Pharmacokinetic analyses showed MMB
      concentrations were too low for TBK1 inhibition. Conclusions MMB was safe and
      well tolerated in combination with nab-P + G. As no OS or PFS benefit vs nab-P +
      G was apparent in context of suboptimal engagement of the target TBK1, this study
      does not support further development of MMB as a first-line therapy in pancreatic
      cancer.

PMID- 30105669
TI  - Guanosine Attenuates Behavioral Deficits After Traumatic Brain Injury by
      Modulation of Adenosinergic Receptors.
AB  - Traumatic brain injury (TBI) is a leading cause of disability worldwide,
      triggering chronic neurodegeneration underlying cognitive and mood disorder still
      without therapeutic prospects. Based on our previous observations that guanosine
      (GUO) attenuates short-term neurochemical alterations caused by TBI, this study
      investigated the effects of chronical GUO treatment in behavioral, molecular, and
      morphological disturbances 21 days after trauma. Rats subject to TBI displayed
      mood (anxiety-like) and memory dysfunction. This was accompanied by a decreased
      expression of both synaptic (synaptophysin) and plasticity proteins (BDNF and
      CREB), a loss of cresyl violet-stained neurons, and increased astrogliosis and
      microgliosis in the hippocampus. Notably, chronic GUO treatment (7.5 mg/kg i.p.
      daily starting 1 h after TBI) prevented all these TBI-induced long-term
      behavioral, neurochemical, and morphological modifications. This neuroprotective
      effect of GUO was abrogated in the presence of the adenosine A1 receptor
      antagonist DPCPX (1 mg/kg) but unaltered by the adenosine A2A receptor antagonist
      SCH58261 (0.05 mg/kg). These findings show that a chronic GUO treatment prevents
      the long-term mood and memory dysfunction triggered by TBI, which involves
      adenosinergic receptors.

PMID- 30105670
TI  - P2X7 Receptors Mediate CO-Induced Alterations in Gene Expression in Cultured
      Cortical Astrocytes-Transcriptomic Study.
AB  - Carbon monoxide (CO) is an endogenous gasotransmitter that limits inflammation
      and prevents apoptosis in several tissues, including the brain. Low
      concentrations of CO are cytoprotective in astrocytes, neurons, and microglia,
      but the underlying molecular mechanisms remain poorly understood. This work aims
      at identification of alterations in gene expression conferred by CO in primary
      cultures of cortical astrocytes, for further disclosure of the molecular
      mechanism of action of the gasotransmitter. Astrocytes were treated with the CO
      releasing molecule CORM-A1 for 40 min, and transcriptional changes were analyzed
      using RNASeq. A total of 162 genes were differentially expressed in response to
      CO treatment, and 7 of these genes were selected for further analysis: FosB,
      Scand1, Rgs10, Actg1, Panx1, Pcbdh21, and Rn18s. The alterations in their
      expression were further validated using qRT-PCR. An increase in FosB protein
      expression was also observed after 40 min of CORM-A1 treatment, as determined by
      a western blot. CO-induced FosB expression and cytoprotection were both abrogated
      in the presence of the P2X7 receptor antagonist A-438079. Furthermore, CORM-A1
      increased phosphorylation of calcium/calmodulin-dependent protein kinase II
      (CaMKII), which is a downstream event of P2X7R activation. The functional
      importance of FosB in CO-induced survival was assessed by knocking down its
      expression with FosB siRNA. Astrocytes were challenged to death with oxidative
      stress and cell viability was assessed 24 h later. Downregulation of FosB did not
      prevent the effects of CO in the inhibition of astrocytic cell death.
      Nevertheless, the transcriptomic changes observed upon treatment of astrocytes
      with CO open new opportunities for further studies on CO cytoprotective pathways.

PMID- 30105672
TI  - Telmisartan Protects a Microglia Cell Line from LPS Injury Beyond AT1 Receptor
      Blockade or PPARgamma Activation.
AB  - The Angiotensin II Receptor Blocker (ARB) Telmisartan reduces inflammation
      through Angiotensin II AT1 receptor blockade and peroxisome proliferator
      activated receptor gamma (PPARgamma) activation. However, in a mouse microglia
      like BV2 cell line, imitating primary microglia responses with high fidelity and
      devoid of AT1 receptor gene expression or PPARgamma activation, Telmisartan
      reduced gene expression of pro-injury factors, enhanced that of anti-inflammatory
      genes, and prevented LPS-induced increase in inflammatory markers. Using global
      gene expression profiling and pathways analysis, we revealed that Telmisartan
      normalized the expression of hundreds of genes upregulated by LPS and linked with
      inflammation, apoptosis and neurodegenerative disorders, while downregulating the
      expression of genes associated with oncological, neurodegenerative and viral
      diseases. The PPARgamma full agonist Pioglitazone had no neuroprotective effects.
      Surprisingly, the PPARgamma antagonists GW9662 and T0070907 were neuroprotective
      and enhanced Telmisartan effects. GW9226 alone significantly reduced LPS toxic
      effects and enhanced Telmisartan neuroprotection, including downregulation of pro
      inflammatory TLR2 gene expression. Telmisartan and GW9662 effects on LPS injury
      negatively correlated with pro-inflammatory factors and upstream regulators,
      including TLR2, and positively with known neuroprotective factors and upstream
      regulators. Gene Set Enrichment Analysis (GSEA) of the Telmisartan and GW9662
      data revealed negative correlations with sets of genes associated with
      neurodegenerative and metabolic disorders and toxic treatments in cultured
      systems, while demonstrating positive correlations with gene sets associated with
      neuroprotection and kinase inhibition. Our results strongly suggest that novel
      neuroprotective effects of Telmisartan and GW9662, beyond AT1 receptor blockade
      or PPARgamma activation, include downregulation of the TLR2 signaling pathway,
      findings that may have translational relevance.

PMID- 30105671
TI  - An Antagonistic Axon-Dendrite Interplay Enables Efficient Neuronal Repair in the
      Adult Zebrafish Central Nervous System.
AB  - Neural insults and neurodegenerative diseases typically result in permanent
      functional deficits, making the identification of novel pro-regenerative
      molecules and mechanisms a primary research topic. Nowadays, neuroregenerative
      research largely focuses on improving axonal regrowth, leaving the regenerative
      properties of dendrites largely unstudied. Moreover, whereas developmental
      studies indicate a strict temporal separation of axogenesis and dendritogenesis
      and thus suggest a potential interdependency of axonal and dendritic outgrowth, a
      possible axon-dendrite interaction during regeneration remains unexplored. To
      unravel the inherent dendritic response of vertebrate neurons undergoing
      successful axonal regeneration, regeneration-competent adult zebrafish of either
      sex, subjected to optic nerve crush (ONC), were used. A longitudinal study in
      which retinal ganglion cell (RGC) dendritic remodeling and axonal regrowth were
      assessed side-by-side after ONC, revealed that-as during development-RGC
      axogenesis precedes dendritogenesis during central nervous system (CNS) repair.
      Moreover, dendrites majorly shrank before the start of axonal regrowth and were
      only triggered to regrow upon RGC target contact initiation, altogether
      suggestive for a counteractive interplay between axons and dendrites after
      neuronal injury. Strikingly, both retinal mechanistic target of rapamycin (mTOR)
      and broad-spectrum matrix metalloproteinase (MMP) inhibition after ONC
      consecutively inhibited RGC synapto-dendritic deterioration and axonal regrowth,
      thus invigorating an antagonistic interplay wherein mature dendrites restrain
      axonal regrowth. Altogether, this work launches dendritic shrinkage as a
      prerequisite for efficient axonal regrowth of adult vertebrate neurons, and
      indicates that molecular/mechanistic analysis of dendritic responses after damage
      might represent a powerful target-discovery platform for neural repair.

PMID- 30105673
TI  - Hotspots and main drivers of fecal pollution in Neusiedler See, a large shallow
      lake in Central Europe.
AB  - To minimize the risk of negative consequences for public health from fecal
      pollution in lakes, the continuous surveillance of microbiological water quality
      parameters, alongside other environmental variables, is necessary at defined
      bathing sites. Such routine surveillance may prove insufficient to elucidate the
      main drivers of fecal pollution in a complex lake/watershed ecosystem, and it may
      be that more comprehensive monitoring activities are required. In this study, the
      aims were to identify the hotspots and main driving factors of fecal pollution in
      a large shallow Central European lake, the Neusiedler See, and to determine to
      what degree its current monitoring network can be considered representative
      spatially. A stochastic and geostatistical analysis of a huge data set of water
      quality data (~ 164,000 data points, representing a 22-year time-series) of
      standard fecal indicator bacteria (SFIB), water quality and meteorological
      variables sampled at 26 sampling sites was conducted. It revealed that the
      hotspots of fecal pollution are exclusively related to sites with elevated
      anthropogenic activity. Background pollution from wildlife or diffuse
      agricultural run-off at more remote sites was comparatively low. The analysis
      also showed that variability in the incidence of SFIB was driven mainly by
      meteorological phenomena, above all, temperature, number of sunny hours, and wind
      (direction and speed). Due to antagonistic effects and temporal undersampling,
      the influence of precipitation on SFIB variance could not be clearly determined.
      Geostatistical analysis did reveal that the current spatial sampling density is
      insufficient to cover SFIB variance over the whole lake, and that the sites are
      therefore in the most part representative of local phenomena. Suggestions for the
      future monitoring and managing of fecal pollution are offered. The applied
      statistical approach may also serve as a model for the study of other such areas,
      and in general indicate a method for dealing with similarly large and
      spatiotemporally heterogeneous datasets.

PMID- 30105674
TI  - Absorption, translocation, and detoxification of Cd in two different castor bean
      (Ricinus communis L.) cultivars.
AB  - Cadmium (Cd) is considered to be the most phytotoxic heavy metal pollutant. The
      selection of castor bean cultivars with Cd tolerance and the exploration of the
      physiological mechanisms involved in Cd tolerance are critical steps for
      improving phytoremediation performance. In this study, a hydroponic experiment
      was used to investigate variations in Cd transportation, chelation, and
      subcellular distribution in two different castor bean cultivars, namely JX-22 and
      ZB-9. Both cultivars had high tolerance index scores, indicating that both
      cultivars were tolerant to Cd. The findings of the present study indicate that Cd
      is significantly more mobile in JX-22 than in ZB-9 during xylem and phloem
      transportation, resulting in the accumulation of Cd in the shoots of JX-22 was
      7.67 times that in ZB-9. Subcellular distribution assessment verified that more
      Cd was bound to the biologically detoxified metal fractions than the metal
      sensitive fractions in JX-22. The contents of the non-protein thiol pool and
      glutathione in the leaves were higher in JX-22 than ZB-9 when exposed to Cd.
      These results indicate that JX-22 has a greater ability to accumulate Cd, and
      well-coordinated physiological changes in JX-22 afford greater Cd tolerance in
      comparison to ZB-9 under Cd exposure, indicating that JX-22 is suitable for use
      in the remediation of Cd-contaminated soils.

PMID- 30105676
TI  - Fate of febantel in the aquatic environment-the role of abiotic elimination
      processes.
AB  - Febantel is widely used anthelmintic drug active against a range of
      gastrointestinal parasites in animals. Despite the fact that it has been detected
      in the aquatic environment, there is no information on its environmental fate.
      Therefore, abiotic elimination processes of febantel in the aquatic environment
      have been studied. The results of direct and indirect photodegradation
      experiments showed that febantel was persistent against solar radiation. Kinetics
      of hydrolytic elimination was pH and temperature dependent with half-lives in the
      range from 210 min to 99 days. Febantel metabolites, fenbendazole and
      fenbendazole sulfone, were found as major degradation products using high
      resolution mass spectrometry. The proposed hydrolytic degradation pathway
      consisted of the base catalyzed hydrolysis followed by consecutive oxidative
      cyclization to the five-membered ring of the benzo-imidazole derivative. Aquatic
      toxicity of febantel and its hydrolytic mixture were evaluated toward the
      luminescence bacteria Vibrio fischeri. Investigation of febantel sorption onto
      river sediments showed that the best agreement was obtained with the linear model
      (R2 > 0.99), while the rate of sorption is the best described with the kinetic
      model of pseudo-second order. The organic carbon-normalized sorption coefficient,
      KOC, ranged from 1490 to 3894 L kg-1 for five sediment samples. The results of
      this research demonstrate that febantel persist in the natural waters and
      potentially could travel far from the source.

PMID- 30105675
TI  - Removal of refractory organic pollutants in reverse-osmosis concentrated leachate
      by Microwave-Fenton process.
AB  - A microwave-Fenton technology was applied to dispose of the reverse-osmosis
      concentrated leachate. Influential factors on the treatment of concentrated
      leachate with the pure Fenton and microwave-Fenton method were investigated. For
      the conventional Fenton process, the removal efficiencies of chemical oxygen
      demand (CODCr), UV254, and the color number (CN) reached 84%, 87%, and 96%,
      respectively, with the biodegradability (BOD5/CODCr) increased from 0.13 to 0.51
      at an initial pH of 5.0, Fe2+ of 0.04 mol/L, a n(H2O2)/n(Fe2+) ratio of 8 after a
      reaction time of 3 h. When incorporating the Fenton process with microwave
      irradiation, a comparative CODCr and UV254, and the CN removal rate of 75%, 83%,
      and 95%, and a high BOD5/CODCr of 0.62 were achieved under a microwave power of
      390 W and an extremely shortened reaction time of only 8 min. Meanwhile, sludge
      quantity showed a reduction of 24.7%, decreased from 8.50 g/L to 6.40 g/L after
      the participation of microwave. In addition, molecular-weight fraction (MWF), UV
      visible spectrum (UV-vis), and 3D-EEM spectrum tests demonstrated that the
      macromolecular and complex organic compounds in the wastewater were significantly
      decomposed into small molecular matters. Our results found that microwave-Fenton
      is a promising technology for concentrated leachate treatment, with much shorter
      reaction time, lower sludge production, and enhanced biodegradability, as well as
      comparative organic matter removal performance.

PMID- 30105678
TI  - ?

PMID- 30105679
TI  - ?

PMID- 30105680
TI  - ?

PMID- 30105677
TI  - Distal Pancreatectomy with Celiac Axis Resection (DP-CAR) for Pancreatic Cancer.
      How I do It.
AB  - Approximately 30% of all pancreatic cancer patients have locally advanced (AJCC
      stage 3) disease. A sub-group of these patients-where the cancer only involves
      the celiac axis-may benefit from distal pancreatectomy with celiac axis resection
      (DP-CAR). Previous studies have shown that DP-CAR offers a survival benefit to a
      selected group of patients with otherwise unresectable pancreatic cancer, when
      performed by experienced pancreatic cancer treatment teams at high-volume
      centers. This article proposes a standardized approach to DP-CAR, including
      routine neoadjuvant (FOLFIRINOX) chemotherapy. This approach to selecting
      patients and performing DP-CAR has the potential to improve short-term outcomes
      and overall survival in selected patients, but it should be reserved for high
      volume centers.

PMID- 30105682
TI  - ?

PMID- 30105681
TI  - ?

PMID- 30105683
TI  - ?

PMID- 30105684
TI  - ?

PMID- 30105685
TI  - ?

PMID- 30105686
TI  - ?

PMID- 30105687
TI  - ?

PMID- 30105689
TI  - ?

PMID- 30105688
TI  - ?

PMID- 30105690
TI  - [Early detection of atrial fibrillation in patients at risk].

PMID- 30105691
TI  - [Operative risk evaluation in the older adult].

PMID- 30105692
TI  - [Delirium and dementia - both cognitive impairment but so different].

PMID- 30105695
TI  - ?

PMID- 30105694
TI  - ?

PMID- 30105693
TI  - [Influence of illness, age and medication: examination of fitness to drive].

PMID- 30105696
TI  - ?

PMID- 30105697
TI  - ?

PMID- 30105698
TI  - ?

PMID- 30105699
TI  - ?

PMID- 30105700
TI  - ?

PMID- 30105702
TI  - ?

PMID- 30105701
TI  - ?

PMID- 30105703
TI  - ?

PMID- 30105704
TI  - ?

PMID- 30105705
TI  - ?

PMID- 30105706
TI  - ?

PMID- 30105708
TI  - ?

PMID- 30105707
TI  - ?

PMID- 30105709
TI  - ?

PMID- 30105710
TI  - ?

PMID- 30105711
TI  - ?

PMID- 30105712
TI  - ?

PMID- 30105713
TI  - ?

PMID- 30105714
TI  - ?

PMID- 30105715
TI  - ?

PMID- 30105716
TI  - ?

PMID- 30105717
TI  - ?

PMID- 30105718
TI  - ?

PMID- 30105719
TI  - ?

PMID- 30105720
TI  - ?

PMID- 30105721
TI  - ?

PMID- 30105722
TI  - ?

PMID- 30105723
TI  - ?

PMID- 30105724
TI  - ?

PMID- 30105725
TI  - ?

PMID- 30105729
TI  - ?

PMID- 30105726
TI  - ?

PMID- 30105727
TI  - ?

PMID- 30105731
TI  - ?

PMID- 30105730
TI  - ?

PMID- 30105732
TI  - ?

PMID- 30105733
TI  - [Acute coronary syndrome].

PMID- 30105734
TI  - MiR-381 negatively regulates cardiomyocyte survival by suppressing Notch
      signaling.
AB  - The mechanisms for cardiomyocyte death in cardiovascular diseases are
      incompletely understood. The aim of this study is to reveal the function of miR
      381 in myocardium infarction (MI)-induced cardiomyocyte apoptosis. We established
      mouse model of MI and cellular models of apoptosis induced by oxidative stress
      (H2O2 and hypoxia/reoxygenation (H/R)). The expression of miR-381 in these models
      was assessed by quantitative reverse transcription polymerase chain reaction (qRT
      PCR); we employed approaches including cell counting kit-8 (CCK-8) assay and flow
      cytometry to evaluate the cell viability and apoptosis. Notch signaling was
      determined by western blot analysis of key signaling components including Notch1
      intracellular domain (ICD), Jag1, and Hes1. The predicted binding of miR-381 to
      Jag1 3' untranslated region (UTR) was validated by luciferase assay. Following
      MI, miR-381 expression was upregulated time dependently in the border zone of
      ischemic area but not in the non-ischemic area. MiR-381 expression was also
      upregulated in cardiomyocytes treated with H2O2 and H/R. Overexpression of miR
      381 exacerbated H2O2- and H/R-induced apoptosis of cardiomyocytes; in contrast,
      inhibition of miR-381 attenuated apoptosis in these conditions. Importantly, in
      vivo delivery of miR-381 antagomir significantly reduced infarction size.
      Moreover, miR-381 negatively regulates the cardioprotective Notch signaling in
      vivo and in vitro, which might be an effect of targeted inhibition of Jag1 by
      itself. These data indicate an essential role of miR-381/Jag1 pathway in
      regulating Notch signaling-mediated cardioprotective effect in cardiomyocytes.
      Our study also provides a potential therapeutic target for cardiovascular
      diseases.

PMID- 30105736
TI  - Effect of water activity, temperature, and incubation period on fungal growth and
      ochratoxin A production on Nyjer seeds.
AB  - Aspergillus fresenii and Aspergillus sulphureus produce ochratoxin A (OTA), which
      is a secondary metabolite of Aspergillus and Penicillium species, with
      nephrotoxic effects and potential carcinogenic activity. The aim of this study
      was to determine the effects of temperature (20, 30, and 37  degrees C), water
      activity (0.82, 0.86, 0.90, 0.94, and 0.98 aw), incubation period (5, 10, 15, and
      30 days) on fungal growth, and OTA production by A. fresenii and A. sulphureus on
      Nyjer oil seeds. There was no fungal growth at 0.82 aw. The two fungal species
      were able to produce OTA from the fifth day of incubation from 0.86 to 0.98 aw
      and temperature 20 to 37  degrees C. Aspergillus fresenii produced the highest
      concentration of OTA (643 MUg/kg) at 0.90 aw and 37  degrees C within 15 days,
      while A. sulphureus produced the highest level of OTA (724 MUg/kg) at 0.98 aw and
      20  degrees C within 10 days. The optimum water activity and temperature for the
      growth of both fungi were similar at 0.94 aw and at 30  degrees C. There was
      statistically significant difference between the levels of OTA production among
      the two fungi. Overall, A. sulphureus produced significantly higher levels of OTA
      (p < 0.05). Higher temperature (37  degrees C) and 0.90-0.94 aw were optimal for
      OTA production by A. fresenii. Our results show that Nyjer seeds can support the
      growth of A. fresenii and A. sulphureus and OTA production, and the two species
      had similar temperature and water activity requirements for growth but different
      requirements for OTA production on Nyjer seeds.

PMID- 30105737
TI  - Genetic diversity and population structure among accessions of Perilla frutescens
      (L.) Britton in East Asia using new developed microsatellite markers.
AB  - SSRs were successfully isolated from the Perilla crop in our current study, and
      used to analyze Perilla accessions from East Asia. Analyses of the clear genetic
      diversity and relationship for Perilla crop still remain insufficient. In this
      study, 40 new simple sequence repeat (SSR) primer sets were developed from RNA
      sequences using transcriptome analysis. These new SSR markers were applied to
      analyze the diversity, relationships, and population structure among 35
      accessions of the two cultivated types of Perilla crop and their weedy types. A
      total of 220 alleles were identified at all loci, with an average of 5.5 alleles
      per locus and a range between 2 and 10 alleles per locus. The MAF (major allele
      frequency) per locus varied from 0.229 to 0.943, with an average of 0.466. The
      average polymorphic information content (PIC) value was 0.603, ranging from 0.102
      to 0.837. The genetic diversity (GD) ranged from 0.108 to 0.854, with an average
      of 0.654. Based on population structure analysis, all accessions were divided
      into three groups: Group I, Group II and the admixed group. This study
      demonstrated the utility of new SSR analysis for the study of genetic diversity
      and population structure among 35 Perilla accessions. The GD of each locus for
      accessions of cultivated var. frutescens, weedy var. frutescens, cultivated var.
      crispa, and weedy var. crispa were 0.415, 0.606, 0.308, and 0.480, respectively.
      Both weedy accessions exhibited higher GD and PIC values than their cultivated
      types in East Asia. The new SSR primers of Perilla species reported in this study
      may provide potential genetic markers for population genetics to enhance our
      understanding of the genetic diversity, genetic relationship and population
      structure of the cultivated and weedy types of P. frutescens in East Asia. In
      addition, new Perilla SSR primers developed from RNA-seq can be used in the
      future for cultivar identification, conservation of Perilla germplasm resources,
      genome mapping and tagging of important genes/QTLs for Perilla breeding programs.

PMID- 30105735
TI  - The Expression Levels of IL-4/IL-13/STAT6 Signaling Pathway Genes and SOCS3 Could
      Help to Differentiate the Histopathological Subtypes of Non-Small Cell Lung
      Carcinoma.
AB  - BACKGROUND: The interleukin (IL)-4/IL-13/signal transducer and activator of
      transcription (STAT) 6 signaling pathway and the SOCS3 gene, one of its main
      regulators, constitute an important link between the inflammation process in the
      epithelial cells and inflammatory-related tumorigenesis. The present study is the
      first to evaluate IL-4, IL-13, STAT6, and SOCS3 mRNA expression in non-small cell
      lung carcinoma (NSCLC) histopathological subtypes. METHODS: Gene expression
      levels were assessed using TaqMan(r) probes by quantitative reverse transcription
      PCR (qRT-PCR) in lung tumor samples and unchanged lung tissue samples. RESULTS:
      Increased expression of IL-4, IL-13, and STAT6 was observed in all
      histopathological NSCLC subtypes (squamous cell carcinoma [SCC], adenocarcinoma
      [AC], and large cell carcinoma [LCC]). Significantly higher expression of IL-13
      and STAT6 (p = 0.019 and p = 0.008, respectively) was found in SCC than in LCC.
      No statistically significant differences were found for IL-4. Significantly
      higher SOCS3 expression was found in LCC than in AC (p = 0.027). A negative
      correlation (rho = -0.519) was observed for the STAT6 and SOCS3 genes in SCC (p =
      0.005). No associations were found between gene expression and tumor staging
      (post-operative Tumor Node Metastasis [pTNM], American Joint Committee on Cancer
      [AJCC]), patients' age, sex, or history of smoking. CONCLUSIONS: As the number of
      LCC cases in our study was quite low, the statistically significant results
      obtained should be confirmed in a larger group of patients, particularly as the
      relationships identified between increased IL-4, IL-13, and STAT6 mRNA expression
      and decreased SOCS3 expression suggest that these genes may serve as potential
      diagnostic markers for differentiating between NSCLC histopathological subtypes.

PMID- 30105738
TI  - In situ gel-forming system for dual BMP-2 and 17beta-estradiol controlled release
      for bone regeneration in osteoporotic rats.
AB  - The aim of this study was to evaluate the bone regeneration capacity of a
      Pluronic(r) F127 (P)-Tetronic(r)1307 (T) and alpha-cyclodextrin (CD)
      supramolecular gel (P-T-CD) in a 11/7/7 ratio containing BMP-2 and 17beta
      estradiol pre-encapsulated in poly-lactide-co-glycolide (PLGA) and poly-lactic
      acid (PLA-S) microspheres, respectively. Ovariectomy combined with dexamethasone
      treatment was used to induce an osteoporotic (OP) animal model of calvaria
      critical size defect in female rats to test the system. The two active substances
      showed a biphasic in vitro release profile characterized by an initial fast phase
      followed by a slow and prolonged release. The bone morphogenetic protein-2 (BMP
      2) in vivo release was faster than in vitro. The in vivo experimental design
      included four groups of sham rats and other four groups of OP rats treated with
      the blank system, BMP-2, and one or two doses of BMP-2 combined with 17beta
      estradiol. After 12 weeks, histological and histomorphometric analyses showed
      that the combined treatment with BMP-2 and 17beta-estradiol did not improve the
      repair response in sham, whereas in OP animals, a significant increase in the
      repair rate was observed with respect to the group treated with BMP-2 alone.
      However, the low values of osteocalcin, showed an immature and poorly mineralized
      new bone in OP animals. The second dose of the system with BMP-2 and 17beta
      estradiol did not improve the repair response in any case.

PMID- 30105739
TI  - Improvement in the Mass Resolution of Single Particle Mass Spectrometry Using
      Delayed Ion Extraction.
AB  - A specific delayed ion extraction (DIE) technique, which combines a standard
      rectangular extraction pulse with an exponential pulse, was introduced for a
      single particle mass spectrometry (SPMS) instrument, and it can focus ions in a
      wide mass range and results in a mass resolution improvement for the mass range
      of the studied ions. The experimental results indicate that the average mass
      resolution for positive ions is about 1000 when the mass-to-charge ratio (m/z) is
      greater than 70, and for negative ions, when the m/z is greater than 70, the
      average resolution can reach 2000. The highest mass resolutions achieved so far
      are 1260 for positive ions and 2400 for negative ions for SPMS, which are very
      beneficial for mass peak interpretation and chemical compound identification. The
      primary applications for atmospheric particle measurements show that the high
      mass resolution of SPMS with the DIE technique is very beneficial for the
      analysis of carbon and metallic element containing particles, and 39K+ with C3H3+
      and 41K+ and C3H5+ in organic particles were successfully differentiated using
      SPMS. The results indicate that SPMS with DIE technique can significantly ease
      mass peak interpretation and improve the mass assignment ability during analysis.
      Furthermore, existing SPMS instruments can be improved by a facile retrofitting
      process to implement the DIE technique. Graphical Abstract The delayed ion
      extraction method shows a great mass resolution improvement for single particle
      mass spectrometry.

PMID- 30105740
TI  - Coupling of a High-Resolution Ambient Pressure Drift Tube Ion Mobility
      Spectrometer to a Commercial Time-of-flight Mass Spectrometer.
AB  - Ion mobility spectrometry provides information about molecular structures of
      ions. Hence, high resolving power allows separation of isomers which is of major
      interest in several applications. In this work, we couple our high-resolution ion
      mobility spectrometer (IMS) with a resolving power of Rp = 100 to a time-of
      flight mass spectrometer (TOF-MS). Besides, the benefit of an increased resolving
      power such an IMS-MS also helps analyzing and understanding the ionization
      processes in IMS. Usually, the coupling between IMS and TOF-MS is realized by
      synchronizing data acquisition of the IMS and MS resulting in two-dimensional
      data containing ion mobility and mass spectra. However, due to peak widths of
      less than 100 MUs in our high-resolution IMS, this technique is not practicable
      due to significant peak broadening during the ion transfer into the MS and an
      insufficient data acquisition rate of the MS. Thus, a novel but simple interface
      between the IMS and MS has been designed which minimizes ion losses, allows
      recording of ion mobility at full IMS resolving power, and enables a shuttered
      transmission of ions into the MS. The interface is realized by replacing the
      Faraday plate used in IMS by a Faraday grid that is shielded by two additional
      aperture grids. For demonstration, positive product ions of benzene, toluene, and
      m-xylene in air are investigated. The IMS is equipped with a radioactive 3H
      source. Besides the well-known product ions M+ and M.NO+, a dimer ion is also
      observed for benzene and toluene, consisting of two molecules and three further
      hydrogen atoms. Graphical Abstract ?.

PMID- 30105741
TI  - Cell-Free Identification of S. cerevisiae Strains by Analysis of Supernatant
      Using LC-MS.
AB  - Current literature shows a gap for methods which can identify yeast sub-species
      (strains or serovars) in samples where there are no viable cells remaining.
      Presented here is a technique for the analysis of yeast supernatant, including
      solid phase extraction, data-dependent acquisition liquid chromatography/mass
      spectrometry (LC-MS), and two chemometric methods to identify and classify yeast
      strains. Five strains of Saccharomyces cerevisiae were successfully identified in
      various stages of growth. In addition, peptide/protein identification was
      performed, without the need for additional data acquisition. Graphical Abstract
      ?.

PMID- 30105742
TI  - Intrapericardial diaphragmatic hernia into the pericardium after esophagectomy: a
      case report.
AB  - BACKGROUND: Intrapericardial diaphragmatic hernia (IPDH), defined as prolapse of
      the abdominal viscera into the pericardium, is a rare clinical condition. This
      case illustrates the possibility of IPDH after esophagectomy with antethoracic
      alimentary reconstruction, although such hernias are extremely rare. IPDH often
      presents with symptoms of bowel obstruction such as abdominal discomfort or
      vomiting. If not properly treated, life-threatening necrosis and/or perforation
      of the herniated contents may occur. CASE PRESENTATION: A 68-year-old Japanese
      man underwent subtotal esophagectomy with three-field lymph node dissection for
      treatment of esophageal cancer. Completion gastrectomy with perigastric lymph
      node dissection was also performed because the patient had previously undergone
      distal partial gastrectomy for treatment of gastric cancer. The alimentary
      continuity was reconstructed using the pedicled jejunal limb through the
      antethoracic route. When we separated the diaphragm from the esophagus and
      removed xiphoid surgically to prevent a pedicled jejunal limb injury, the
      pericardium was opened. The patient was readmitted to our hospital because of
      abdominal discomfort and vomiting 6 months after the esophagectomy. A diagnosis
      of IPDH after esophagectomy was made. The patient was treated by primary closure
      of the diaphragmatic defect using vertical mattress sutures and additional
      reinforcement of the closing defect using a graft harvested from the rectus
      abdominis posterior sheath. The postoperative course was uneventful, and he was
      discharged on the seventh day after hernia repair. CONCLUSIONS: This patient's
      clinical course provides two important clinical suggestions. First, we must be
      aware of the possibility of iatrogenic IPHD after esophagectomy with antethoracic
      alimentary reconstruction. Second, a graft from the rectus abdominis posterior
      sheath is beneficial in the treatment of IPDH.

PMID- 30105743
TI  - Personality Process-Structure Duality: Reply to Two Commentaries.
AB  - In two commentaries, Kostromina and Grishina (2018) and Mironenko (2018) offered
      constructive thoughts and questions in response to an article by Giordano (2018,
      Culture & Psychology, 23, 502-518) on the merits of an approach to understanding
      individual personality that focuses on the processes rather than structures of
      personality. In this reply, the authors seek to clarify some of the points made
      in the original article. The authors also describe a personality process
      structure duality, whereby personality is conceptualized in terms of processes or
      structures based on the methods used to study it. If the goal is to understand
      the dynamic and emergent properties of individual personality, the authors
      continue to argue for the merits of a process-centric approach and the avoidance
      of structural thinking.

PMID- 30105745
TI  - Standardized Questionnaire for the Measurement, Valuation, and Estimation of
      Costs of Informal Care Based on the Opportunity Cost and Proxy Good Method.
AB  - Costs of informal care account for a significant component of total societal
      costs for many chronic and disabling illnesses. Yet, costs associated with the
      provision of informal care is seldom included in economic evaluations of new
      health technologies, increasing the risk of suboptimal decisions on the
      allocation of resources from the perspective of society. Our objective was to
      propose a standardized questionnaire for the measurement, valuation, and
      estimation of caregiver indirect (productivity) and informal care costs as
      separate mutually exclusive subsets of total costs in cost-of-illness studies and
      as an input to economic evaluations from the societal perspective. We developed a
      questionnaire for data collection and step-by-step analysis procedures for
      resource valuation and cost estimation. Data concerning absenteeism from work and
      time devoted to informal care were recorded using the recall method. Indirect
      (productivity) and paid informal care costs were valued and estimated according
      to the human-capital approach as the loss of production. Unpaid informal care
      costs were valued and estimated as the loss of leisure time quantified using the
      opportunity cost and proxy good method. The new questionnaire, titled the
      Caregiver Indirect and Informal Care Cost Assessment Questionnaire, contains 13
      questions regarding caregiver current and previous work status, productivity, and
      the provision of informal care (stratified by time devoted to household
      activities, personal care, practical support, and emotional support). The
      proposed questionnaire should be helpful to inform the design, implementation,
      and execution of future cost-of-illness studies and economic evaluations from the
      perspective of society.

PMID- 30105744
TI  - Patient Understanding of the Neuropsychiatric Risks Associated with Branded
      Bupropion Hydrochloride Products Used for Smoking Cessation.
AB  - BACKGROUND: Bupropion hydrochloride (Zyban) is an effective aid to smoking
      cessation; however, its use has previously been associated with neuropsychiatric
      adverse events. Here we report results of the patient Knowledge, Attitudes, and
      Behavior survey that forms part of the Year 7 Risk Evaluation and Mitigation
      Strategy (REMS) assessment for Zyban. OBJECTIVE: Assess participants'
      understanding of the neuropsychiatric risks associated with branded bupropion
      hydrochloride products that are used for smoking cessation, as described in the
      Medication Guides. METHODS: A cross-sectional study was conducted among patients
      >= 18 years of age, who had used or filled a prescription for branded bupropion
      hydrochloride for smoking cessation in the past 6 months. Participants were
      recruited through an online panel, pharmacy network, or by healthcare provider
      referral, and invited to complete a survey containing questions regarding the
      risks associated with the use of branded bupropion hydrochloride products, and
      whether they had received and read the Medication Guide. The study aimed for >=
      80% of participants to respond correctly to each question regarding
      neuropsychiatric risks. RESULTS: From the 50,985 survey invitations distributed,
      1017 participants responded, of whom 144 were eligible and 142 completed the
      survey. Over 80% of participants correctly responded to most neuropsychiatric
      risk questions. Approximately three-quarters of participants received the
      Medication Guide when they last filled their prescription, of whom over half read
      the Medication Guide at that time. CONCLUSIONS: Participants enrolled in this
      Year 7 REMS survey had good understanding of the neuropsychiatric risks
      associated with using branded bupropion hydrochloride products for smoking
      cessation.

PMID- 30105746
TI  - Cancer metastasis versus stem cell homing: Role of platelets.
AB  - One of the major obstacles in achieving a successful stem cell therapy is
      insufficient homing of transplanted cells. To overcome this obstacle,
      understanding the underlying mechanisms of stem cell homing is of obvious
      importance. Central to this review is the concept that cancer metastasis can be
      viewed as a role model to build up a comprehensive concept of stem cell homing.
      In this novel perspective, the prosurvival choices of the cancerous cells in the
      bloodstream, their arrest, extravasation, and proliferation at the secondary site
      can be exploited in favor of targeted stem cell homing. To date, tumor cells have
      been found to employ a wide variety of strategies to promote metastasis. One of
      these strategies is through their ability to activate platelets and subsequently
      activated platelets serve cancer cell survival and metastasis. Accordingly, in
      the first part of this review the roles of platelets in cancer metastasis as well
      as stem cell homing are discussed. Next, we provide some lessons learned from
      cancer metastasis in favor of developing strategies for improvement of stem cell
      homing with emphasis on the role of platelets. Based on direct or indirect
      evidence from metastasis, strategies such as manipulation of stem cells to
      enhance interaction with platelets, preconditioning-pretreatment of stem cells
      with platelets in vitro, and coinjection of both stem cells and platelets are
      proposed to improve stem cell homing.

PMID- 30105747
TI  - Sex hormones, erectile dysfunction, and psoriasis; a bad friendship!
AB  - BACKGROUND: Sex hormones may play a major role in psoriasis pathogenesis due to
      their biological and immunological effects on skin. Psoriasis also has a
      significant impact on patients' sexual function and thus their quality of life.
      AIM: In the present study, we investigated serum sex hormones and erectile
      function in male psoriasis patients compared with healthy controls and correlated
      these findings with various disease parameters. METHODS: Serum total testosterone
      and estradiol were measured by an ELISA technique in 50 male patients with
      psoriasis and 30 healthy controls. The erectile function of all subjects was
      assessed by the international index of erectile function version-5. RESULTS:
      Patients with psoriasis showed a significant lower serum level of total
      testosterone, higher level of estradiol, and impaired erectile function relative
      to healthy controls. CONCLUSION: The detected hormonal disturbance in male
      psoriasis patients may be a cause of the associated erectile dysfunction beside
      the known effect of chronic systemic disease on patients' erectile function.

PMID- 30105748
TI  - Automated Time Series Modeling for Piezometers in the National Database of the
      Netherlands.
AB  - The Geological Survey of the Netherlands (TNO-GSN) maintains a public national
      database of groundwater head observations. Transfer function-noise modeling has
      been applied to the time series in order to extract the impulse response
      functions for precipitation and evaporation for each piezometer. An automated
      procedure has been developed to assess the quality of the time series and of the
      models. The time series models of sufficient quality offer far more homogeneous
      data on the piezometric head than the original measurements. This allows for
      improved mapping of the head at a specific date or of characteristics of the head
      like average summer or winter levels. Also, the separation of precipitation and
      evaporation from other influences is useful for groundwater management and
      policy. The individual time series models are available online with interactive
      graphics (https://www.grondwatertools.nl/grondwatertools-viewer). The spatial
      patterns of the impulse response function characteristics can support analyses of
      the groundwater system.

PMID- 30105749
TI  - Acupuncture and acupressure for premenstrual syndrome.
AB  - BACKGROUND: Acupuncture has a history of traditional use in China for women's
      health conditions including premenstrual syndrome (PMS), but its effectiveness
      for this condition remains unclear. This review examined the available evidence
      supporting the use of acupuncture or acupressure to treat PMS. OBJECTIVES: To
      evaluate the effectiveness and safety of acupuncture or acupressure for women
      with PMS or premenstrual dysphoric disorder (PMDD). SEARCH METHODS: We searched
      the Cochrane Gynaecology and Fertility Specialised Register, Cochrane Central
      Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, AMED, PsycINFO,
      CINAHL (from inception to 21 September 2017), two clinical trial databases (from
      their inception to 21 September 2017), and four electronic databases in China
      (from their inception to 15 October 2017): Chinese Biomedical Literature database
      (CBM), China National Knowledge Infrastructure (CNKI), VIP information/ Chinese
      Scientific Journals database and WANFANG. Reference lists from included articles
      were handsearched. SELECTION CRITERIA: We included studies if they randomised
      women with PMS and associated disorders (PMDD and late luteal phase dysphoric
      disorder/LPDD) to receive acupuncture or acupressure versus sham, usual
      care/waiting-list control or pharmaceutical interventions mentioned by the
      International Society for Premenstrual Disorders (ISPMD). If acupuncture or
      acupressure were combined with another therapy, these studies were also included
      where the additional therapy was the same in both groups. Cross-over studies were
      eligible for inclusion, but only data from the first phase could be used. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected the studies,
      assessed eligible studies for risk of bias, and extracted data from each study.
      Study authors were contacted for missing information. The quality of the evidence
      was assessed using GRADE. Our primary outcomes were overall premenstrual symptoms
      and adverse events. Secondary outcomes included specific PMS symptoms, response
      rate and quality of life. MAIN RESULTS: Five trials (277 women) were included in
      this review. No trials compared acupuncture or acupressure versus other active
      treatments. The number of treatment sessions ranged from seven to 28. The quality
      of the evidence ranged from low to very low quality, the main limitations being
      imprecision due to small sample sizes and risk of bias related to detection bias
      and selective reporting.Acupuncture versus sham acupunctureAcupuncture may
      provide a greater reduction in mood-related PMS symptoms (mean difference (MD) 
      9.03, 95% confidence interval (CI) -10.71 to -7.35, one randomised controlled
      trial (RCT), n = 67, low-quality evidence) and in physical PMS symptoms (MD 
      9.11, 95% CI -10.82 to -7.40, one RCT, n = 67, low-quality evidence) than sham
      acupuncture, as measured by the Daily Record of Severity of Problems scale
      (DRSP). The evidence suggests that if women have a mood score of 51.91 points
      with sham acupuncture, their score with acupuncture would be between 10.71 and
      7.35 points lower and if women have a physical score of 46.11 points, their score
      with acupuncture would be between 10.82 and 7.4 points lower.There was
      insufficient evidence to determine whether there was any difference between the
      groups in the rate of adverse events (risk ratio (RR) 1.74, 95% CI 0.39 to 7.76,
      three RCTs, n = 167, I2 = 0%, very low-quality evidence).Specific PMS symptoms
      were not reportedThere may be little or no difference between the groups in
      response rates. Use of a fixed-effect model suggested a higher response rate in
      the acupuncture group than in the sham group (RR 2.59, 95% CI 1.71 to 3.92;
      participants = 100; studies = 2; I2 = 82%), but owing to the high heterogeneity
      we tested the effect of using a random-effects model, which provided no clear
      evidence of benefit for acupuncture (RR 4.22, 95% CI 0.45 to 39.88, two RCTs, n =
      100, I2 = 82%, very low-quality evidence).Acupuncture may improve quality of life
      (measured by the WHOQOL-BREF) compared to sham (MD 2.85, 95% CI 1.47 to 4.23, one
      RCT, n = 67, low-quality evidence).Acupuncture versus no treatmentDue to the very
      low quality of the evidence, we are uncertain whether acupuncture reduces PMS
      symptoms compared to a no treatment control (MD -13.60, 95% CI -15.70 to -11.50,
      one RCT, n = 14).No adverse events were reported in either group.No data were
      available on specific PMS symptoms, response rate or quality of life
      outcomes.Acupressure versus sham acupressureWe found low-quality evidence that
      acupressure may reduce the number of women with moderate to severe PMS symptoms
      at the end of the trial compared to sham acupressure (RR 0.64 95% CI 0.52 to
      0.79, one RCT, n = 90, low-quality evidence). The evidence suggests that if 97
      women out of 100 in the sham acupressure group had moderate to severe PMS
      symptoms, the number of women in the acupressure group with moderate to severe
      symptoms would be 50 to 76 women.Acupressure may improve both physical (MD 24.3,
      95% CI 17.18 to 31.42, one RCT, n = 90, low-quality evidence) and mental (MD
      17.17, 95% CI 13.08 to 21.26, one RCT, n = 90, low-quality evidence) quality of
      life.No data were available on adverse events, specific symptoms or response
      rates. AUTHORS' CONCLUSIONS: The limited evidence available suggests that
      acupuncture and acupressure may improve both physical and psychological symptoms
      of PMS when compared to a sham control. There was insufficient evidence to
      determine whether there was a difference between the groups in rates of adverse
      events.There is no evidence comparing acupuncture or acupressure versus current
      ISPMD recommended treatments for PMS such as selective serotonin reuptake
      inhibitors (SSRIs). Further research is required, using validated outcome
      measures for PMS, adequate blinding and suitable comparator groups reflecting
      current best practice.

PMID- 30105750
TI  - An inside look at prurigo pigmentosa: case report from Ukraine.

PMID- 30105751
TI  - Phenotypic, molecular and pathological characterization of motile aeromonads
      isolated from diseased fishes cultured in Uruguay.
AB  - Information about motile aeromonads from aquaculture systems of the Neotropical
      region is scarce. The aim of this study was to characterize motile Aeromonas
      isolated from ornamental and consumable fishes cultured in Uruguay. Biochemical
      and molecular methods were used for species identification. Antimicrobial
      susceptibility and the presence of virulence genes were evaluated. Genetic
      diversity was analysed by rep-PCR, and virulence of the most representative
      isolates was determined by calculating the fifty lethal dose in experimentally
      challenged fish (Australoheros facetus). Aeromonas hydrophila and A. veronii were
      the most prevalent identified species (38.2% and 32.4%, respectively), whereas A.
      allosacharophila, A. bestiarium, A. caviae and A. punctata were less prevalent.
      This study constitutes the first report of these last four species in Uruguay.
      All isolates were resistant to at least three antimicrobials, and 82.3% of them
      showed multidrug resistance. Virulence genotypes were correlated with the
      Aeromonas species and haemolytic activity. The genotype act+/alt+/ast+/ela+/lip+
      was the most prevalent (26.5%). A correlation between virulence genotypes and
      Aeromonas species was found. A. punctata showed a clonal structure according to
      rep-PCR analysis, whereas other species showed high genetic diversity. The number
      of virulence genes of the isolates was related with virulence according to the
      experimental challenge assays.

PMID- 30105752
TI  - Speckle tracking carotid artery circumferential strain is a marker of arterial
      sclerosis but not coronary atherosis.
AB  - PURPOSE: Circumferential speckle tracking carotid artery strain is a novel method
      of quantifying vessel wall stiffness. We hypothesized that carotid wall stiffness
      would be associated with carotid intimal medial thickening (a medial process
      associated with risk factors), but not coronary artery disease (an intimal
      process). METHODS: Bilateral carotid artery ultrasound was conducted on
      outpatients who had previously undergone elective coronary angiography. Mean
      carotid artery far wall circumferential strain (FWCS) was assessed for
      correlations with coronary angiographic stenosis, cardiac risk factors, carotid
      intima-media thickness (CIMT), and carotid plaque. RESULTS: One hundred and sixty
      five (165) patients were studied. No significant association was found between
      the presence of coronary artery disease on angiography and mean FWCS. FWCS was
      higher in current tobacco smokers. In addition, carotid strain was found to
      decrease with increased age (r = -0.33, P < 0.001). When adjusted for pulse
      pressure (PP), FWCS/PP was negatively correlated with mean CIMT (r = -0.29, P =
      0.002) and bulb maximum plaque height (r = -0.27, P = 0.004). Hypertension and
      diabetes were associated with decreased FWCS/PP (increased wall stiffness).
      CONCLUSIONS: While no clear relationship between carotid strain and coronary
      artery disease was observed, increased CIMT, carotid plaque, and cardiac risk
      factors were associated with decreased carotid strain. Further work is required
      to explore the relationship between carotid strain and cardiovascular events.

PMID- 30105753
TI  - Composite chronic myeloid leukemia and essential thrombocythemia with BCR-ABL1
      fusion and CALR mutation.

PMID- 30105754
TI  - Social practice, plural lifestyles and health inequalities in the United Kingdom.
AB  - Persistent health inequalities pose a continued research and policy challenge in
      the United Kingdom and elsewhere. Current approaches to health research and
      promotion are predicated on a distinction between wider, social structural causes
      and individual, health-related behaviours often conceived of as lifestyle
      choices. Drawing on Bourdieu's theory of social practice, this paper develops an
      integrated perspective by observing associations between health and structured
      lifestyle practices. Using the UK Understanding Society household survey, a
      taxonomy of eight lifestyle clusters is identified, which exhibit significant
      health inequalities on a number of indicators. But the plurality of practices and
      subjective orientations inherent in the taxonomy reveals a finer, more complex
      differentiation of the social gradient in health. In addition, lifestyle appears
      to at least in parts mediate the relationship between social, material conditions
      and health. A feature of the taxonomy is that it admits a relational and
      contextual apprehension of health-relevant, behavioural aspects within a more
      holistic notion of lifestyles. Based on this view, strategic approaches can be
      developed that respond to group-specific situations and pathways and their
      varying roots in upstream or downstream domains of policy.

PMID- 30105756
TI  - HNA-1, -3, -4, and -5 genotyping using multiplex PCR among southern Thais:
      Developing continual HNA-1 null detection.
AB  - BACKGROUND: Antibodies against human neutrophil antigens (HNAs) are involved in
      various clinical conditions including transfusion-related acute lung injury and
      auto/alloimmune neutropenia. We aimed to determine HNA-1, -3, -4, and -5
      frequencies among southern Thais using multiplex PCR and to develop HNA-1 null
      detection. METHODS: Samples obtained from 427 southern Thai blood donors were
      genotyped HNA-1, -3, -4, and -5 using multiplex PCR and compared their allele
      frequencies with those previously reported in Thai populations. HNA-1 null
      samples were tested by newly developed PCR-SSP and PCR-RFLP and confirmed by DNA
      sequencing. RESULTS: The frequencies of FCGR3B*01, FCGR3B*02, FCGR3B*03,
      SLC44A2*01, SLC44A2*02, ITGAL*01, and ITGAL*02 among southern Thais differed from
      other Thai populations, except ITGAM*01 and ITGAM*02 frequencies. Two samples
      without specific fragments of FCGR3B*01, FCGR3B*02, and FCGR3B*03 tested by
      multiplex PCR were confirmed by PCR-RFLP to identify FCGR3B deficiency (HNA-1
      null). Moreover, to reduce test steps, the newly developed PCR-SSP for FCGR3B
      deficiency was validated and tested in all samples and the results were in
      agreement with DNA sequencing. CONCLUSIONS: This was the first study to report
      HNA-1, -3, -4, and -5 frequencies among southern Thais. The indeterminate results
      of multiplex PCR for HNA-1 genotyping led to establish HNA-1 null detection using
      PCR-SSP, which is simple, convenient and cost-effective and can be used to
      identify FCGR3B deficiency.

PMID- 30105755
TI  - Splenectomy in patients with chronic myelomonocytic leukemia: Indications,
      histopathological findings and clinical outcomes in a single institutional series
      of thirty-nine patients.
AB  - In a 28-year period, 39 (7%) patients with chronic myelomonocytic leukemia (CMML)
      (median age 66 years, 64% male) underwent a splenectomy at our institution.
      Primary indications for splenectomy were refractory thrombocytopenia (36%),
      progressive spleen related symptoms (33%), emergent splenectomy for splenic
      rupture (21%), refractory anemia (8%), and prior to allogeneic stem cell
      transplant (3%). Eleven (28%) patients had anemia at the time of splenectomy, of
      which 3 (27%) were autoimmune. The median time to splenectomy from CMML diagnosis
      was 6 months (0-40); perioperative morbidity and mortality rates were 43% and
      13%, while the median postsplenectomy survival was 25 months (11-38). Durable
      remission in spleen related symptoms, thrombocytopenia, complications from
      splenic rupture, and anemia were achieved in 85%, 50%, 62%, and 21% of patients,
      respectively. Perioperative morbidity (n = 30) included infections/sepsis in 6
      (20%), intraabdominal bleeding in 4 (13%), venous thromboembolism (VTE) in 3
      (10%), and acute lung injury in 2 (7%) patients. The median duration of hospital
      stay was 6 days (1-25), with 5 deaths occurring secondary to respiratory failure
      (n = 2), multiorgan dysfunction (n = 2) and hemorrhagic shock (n = 1). There was
      no difference in overall survival between CMML patients that underwent
      splenectomy, in comparison to those that did not. Unlike in myelofibrosis, portal
      hypertension was not an indication for splenectomy and no patients developed post
      splenectomy thrombocytosis. In conclusion, apart from being a lifesaving emergent
      modality in the event of splenic rupture, splenectomy has an important palliative
      role in patients with CMML, with significant and durable improvements in spleen
      related symptoms and refractory cytopenias.

PMID- 30105758
TI  - Evaluation of the performance of two real-time PCR assays for detecting
      Mycobacterium species.
AB  - BACKGROUNDS: Rapid discrimination between Mycobacterium tuberculosis (MTB) and
      nontuberculous mycobacteria (NTM) is critical for patient treatment and to avoid
      unnecessary expenditure on infection control. Because real-time PCR assays
      distinguish MTB from NTM, we evaluated the performance of two real-time PCR
      assays (AdvanSure and PowerChek). METHODS: This study used 143 DNA samples from
      respiratory specimens which were collected based on routine PCR results using
      Anyplex kit. A total of 87 positive samples (65 MTB and 22 NTM) and 56 negative
      samples were collected consecutively during 6 months and 1 month, respectively.
      The diagnostic performance of PCR assays (AdvanSure and PowerChek) was
      retrospectively analyzed based on the results of conventional mycobacterial tests
      and routine PCR assay. RESULTS: Based on culture results, the
      sensitivities/specificities of AdvanSure and PowerChek were 90.7%/87.6% and
      92.6%/85.4%, respectively, for MTB detection. For PCR-positive specimens, the
      quantification cycle (Cq) values of smear-negative specimens were higher than
      those of the smear-positive specimens (P < 0.001). As expected, the two PCR
      assays had the same sensitivities for NTM detection, viz. 90.0%, and their
      specificities were 99.2% and 98.4%, respectively. The overall agreement rate
      between the three PCR assays was 96.5% for MTB and 97.9% for NTM. CONCLUSION: The
      sensitivities of PCR assays in our study might be overestimated, because this
      study enrolled relatively lower number of PCR-negative samples which potentially
      missed PCR-negative but culture-positive specimens. However, the two real-time
      PCR assays for detecting MTB and NTM perform equally well in relative performance
      evaluation and their Cq values can be considered suitable for predicting smear
      positive specimens.

PMID- 30105757
TI  - Diastolic dysfunction in tetralogy of Fallot: Comparison of echocardiography with
      catheterization.
AB  - BACKGROUND: Right ventricular (RV) systolic dysfunction has been associated with
      adverse outcomes in tetralogy of Fallot (TOF). However, the role and etiology of
      diastolic dysfunction remain incompletely defined. We assessed the association
      between traditional echocardiographic measures of diastolic function with
      catheter-based RV end-diastolic pressure (RVEDP) and identified clinical
      characteristics independently associated with diastolic dysfunction. METHODS:
      Single-center, retrospective cohort study of surgically repaired TOF patients
      undergoing cardiac catheterization with echocardiograms within 3 months prior to
      the catheterization. Tricuspid inflow and tissue Doppler measurements (E/A, E/e',
      and deceleration time) defined diastolic dysfunction, graded as impaired
      relaxation, pseudonormal, or restrictive physiology. Regression analyses tested
      associations between echocardiographic parameters, RVEDP, and clinical
      characteristics. RESULTS: Ninety-four subjects were included. Catheterization age
      was 8.9 years (interquartile range 4.4, 15.9). RVEDP was 9.5 +/- 2.5 mm Hg. Sixty
      one (65%) subjects had echocardiographic evidence of diastolic dysfunction. RVEDP
      was not associated with echocardiographic parameters of diastolic function (grade
      of dysfunction, E/e', or E/A). Higher RVEDP was associated with larger right
      atrial and RV end-diastolic area, independently of weight and degree of pulmonary
      or tricuspid regurgitation, though was not associated with indexed right atrial
      or RV end-diastolic area. Greater number of interim procedures was associated
      with higher RVEDP, E/e', and the presence of diastolic dysfunction by
      echocardiography. CONCLUSIONS: Diastolic dysfunction, as determined by
      echocardiography-derived and catheter-based (RVEDP) measures, is prevalent in
      this TOF population. These measures are not associated with each other;
      therefore, echocardiographic parameters of diastolic function are not reflective
      of RVEDP. The development of noninvasive parameters that correlate with filling
      pressures is required.

PMID- 30105759
TI  - Genome-scale analysis to identify prognostic markers and predict the survival of
      lung adenocarcinoma.
AB  - Lung cancer is one of the most malignant cancers worldwide, and lung
      adenocarcinoma (LAC) remains the most common histologic subtype. However, the
      functional significance of RNA expression-based prognosis prediction in LAC is
      still unclear and needs to be further studied. By utilizing the Cox multivariate
      regression, we established a risk score staging system to predict the outcome of
      patients with LAC and subsequently identified 10 genes, including PTPRH, OGFRP1,
      LDHA, AL365203.1, LINC02178, AL512488.1, LINC01312, AL353746.1, DRAXINP1, and
      LINC02310, which were closely related to the prognosis of patients with LAC. The
      identified genes allowed us to classify patients into high-risk group with poor
      outcome and low-risk group with better outcome. Compared with other clinical
      factors, the risk score performs better in predicting the outcome of LAC
      patients. We used Gene-Set Enrichment Analysis to identify the differences
      between the 2 groups in biological pathways. In conclusion, we identified 10
      genes by utilizing Cox regression model and developed a risk staging model for
      LAC, which might prove significant for the clinical management of LAC patients.

PMID- 30105761
TI  - Prevalence of attention deficit hyperactivity disorder symptoms in patients with
      schizophrenia.
AB  - OBJECTIVE: To investigate the frequency of childhood and adult attention deficit
      hyperactivity disorder (ADHD) symptoms in a cohort of patients with schizophrenia
      (SCZ). METHODS: A systematic review was conducted to evaluate existing evidence.
      Two self-report questionnaires were used to investigate adult ADHD and childhood
      ADHD symptoms in 126 patients with ICD-10 diagnoses of SCZ. RESULTS: Five studies
      were included in the systematic review, with the prevalence of childhood and
      adult ADHD in SCZ subjects ranging between 17-57% and 10-47% respectively. Within
      our cohort, 47% of patients reported positive screening for ADHD symptoms either
      in childhood or adulthood. 23% reported symptomatology consistent with both
      childhood and adult ADHD. CONCLUSIONS: We demonstrate a greater presence of ADHD
      symptomatology in SCZ compared to that reported for ADHD in the general
      population. Our findings highlight the importance of improved clinical assessment
      and treatment considerations in a subgroup of patients with SCZ.

PMID- 30105760
TI  - Characterization of voiding function and structural bladder changes in a rat
      model of neurogenic underactive bladder disease.
AB  - OBJECTIVES: To create an animal model for neurogenic underactive bladder disease
      (UAB) and identify markers to describe secondary myogenic changes in the bladder
      wall. MATERIALS AND METHODS: Male rats underwent either bilateral pelvic nerve
      injury or sham surgery. Four weeks after surgery functional evaluation was
      performed and tissue was harvested. Functional evaluation consisted of analysis
      of voiding pattern, 24-h urine collection in a metabolic cage, in vivo cystometry
      and in-vitro contractile function assessment. PCR and immunohistochemical
      localization of different smooth muscle cell and extracellular matrix markers was
      performed on bladder strips. RESULTS: After pelvic nerve injury, dry bladder
      weight increased and voiding contractions were absent, resulting in overflow
      incontinence. In-vitro contractile response to carbachol was decreased. This was
      paired with an upregulation of synthetic smooth muscle cell (SMC) markers mRNA
      expression such as retinol binding protein 1 (RBP1), myosin 10 (MYH10) and
      osteopontin (OPN), and a downregulation of contractile SMC marker smoothelin
      (SMTL). The SMTL/OPN mRNA ratio was 50 times higher in sham bladders compared to
      PNI bladders. CONCLUSIONS: The loss of in-vivo and in-vitro contractile function
      following pelvic nerve transection is characterized by a switch from a
      contractile to synthetic SMC phenotype, which is best characterized by the ratio
      SMTL/OPN mRNA expression. Modulating this phenotypical switch is a potential
      target for the development of UAB therapy. We suggest for the first time a set of
      markers that may be useful to evaluate therapeutic strategies on improvements in
      bladder wall structure.

PMID- 30105763
TI  - ST-segment elevation myocardial infarction possibly caused by thromboembolism
      from left atrial appendage thrombus after incomplete surgical ligation.
AB  - Coronary embolism (CE) is the underlying cause of 3% of acute coronary syndromes
      but is frequently overlooked in the differential diagnoses of acute coronary
      syndromes. The CE may be direct (left sided from the native or prosthetic heart
      valve, the left atrium, left atrial appendage or pulmonary venous bed),
      paradoxical (from the venous circulation through a patent foramen ovale, atrial
      septal defect, ventricular septal defects, cyanotic congenital heart defects or
      pulmonary arteriovenous malformations), or iatrogenic (following cardiac
      interventions. In patients with atrial fibrillation (AF), left atrial appendage
      (LAA) ligation during mitral valve surgery has long been recommended to decrease
      the future risk of embolic events such as myocardial infarction or ischemic
      stroke. Recently, Aryana et al reported that in patients with AF who underwent
      surgical ligation of LAA, the presence of incomplete ligation was associated with
      a significantly higher risk of stroke/systemic embolization than complete
      ligation (24% vs 2%).

PMID- 30105762
TI  - Epithelial-to-mesenchymal transition signature assessment in colorectal cancer
      quantifies tumour stromal content rather than true transition.
AB  - The process of epithelial-to-mesenchymal transition (EMT) in cancer is a well
      described process whereby epithelial tumour cells undergo molecular/phenotypic
      changes and transition to a mesenchymal biology. To aid in the transcriptional
      characterisation of this process, gene expression signatures have been developed
      that attribute a relative EMT score to samples in a given cohort. We demonstrate
      how such EMT signatures can identify epithelial cell line models with high levels
      of transition but also highlight that, unsurprisingly, fibroblast cell lines,
      which are inherently mesenchymal, have a higher EMT score relative to any
      epithelial cell line studied. In line with these data, we demonstrate how
      increased tumour stromal composition, and reduced epithelial cellularity,
      significantly correlates with increasing EMT signature score, which is evident
      using either in silico subtyping analysis (p < 0.00001) or in situ
      histopathological characterisation (p < 0.001). Considered together, these
      results reinforce the importance not only of interdisciplinary research to
      correctly define the nature of EMT biology but also the requirement for a cadre
      of multidisciplinary researchers who can analyse and interpret the underlying
      pathological, bioinformatic and molecular data that are essential for advancing
      our understanding of the malignant process. (c) 2018 The Authors. The Journal of
      Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of
      Great Britain and Ireland.

PMID- 30105765
TI  - A Tool for Connection: Using the Person-of-the-Therapist Training (POTT) Model in
      Emotionally Focused Couple Therapy Supervision.
AB  - Emotionally Focused Couple Therapy (EFT) was developed based on the premise that
      couples get stuck in negative cycles fueled by their underlying primary emotions
      and unmet attachment needs (Johnson [2004], Creating connection: The practice of
      Emotionally Focused Couple Therapy). EFT therapists need to stay in touch with
      and regulate their own emotions when the tension rises in the sessions, while
      still staying open and vulnerable to their clients. Person-of-the-Therapist
      Training model (Aponte & Kissil [2016], The person of the therapist training
      model: Mastering the use of self) aims to increase therapists' understanding,
      awareness, and acceptance of their own personal issues to create a more empathic
      connection with their clients. In this manuscript, the authors create a roadmap
      for EFT supervisors to use the POTT model in supervision as a tool to enhance
      their supervisees' connection to their clients and effectiveness of their
      interventions.

PMID- 30105764
TI  - Left ventricular noncompaction in patients with coronary artery disease:
      Preliminary analysis of echocardiographic findings.
AB  - We retrospectively analyzed the echocardiographic findings of eight patients with
      left ventricular noncompaction (LVNC) and concurrent coronary artery disease.
      This study was conducted in Yijishan Hospital between January 2012 and May 2017.
      Of the eight patients, six were diagnosed with coronary arterial atherosclerosis,
      one patient with coronary pulmonary fistula, and one with coronary myocardial
      bridge. Regional wall motion abnormalities were detected in all patients.
      Echocardiography can provide significant information about LVNC in patients with
      coronary artery disease. However, whether regional wall motion abnormalities are
      caused by coronary artery disease or noncompaction of the myocardium remains
      unknown in most patients.

PMID- 30105766
TI  - Development of a Minimal Photosystem for Hydrogen Production in Inorganic
      Chemical Cells.
AB  - Inorganic chemical cells (iCHELLs) are compartment structures consisting of
      polyoxometalates (POMs) and cations, offering structured and confined reaction
      spaces bounded by membranes. We have constructed a system capable of efficient
      anisotropic and hierarchical photo-induced electron transfer across the iCHELL
      membrane. Mimicking photosynthesis, our system uses proton gradients between the
      compartment and the bulk to drive efficient conversion of light into chemical
      energy, producing hydrogen upon irradiation. This illustrates the power of the
      iCHELL approach for catalysis, where the structure, compartmentalisation and
      variation in possible components could be utilised to approach a wide range of
      reactions.

PMID- 30105767
TI  - Evaluation of clarity of presentation and applicability of monitoring
      instructions for patients using lithium in clinical practice guidelines for
      treatment of bipolar disorder.
AB  - OBJECTIVES: Clinical practice guidelines (CPGs) for treatment of bipolar disorder
      (BD) aim to provide guidance to health care professionals on monitoring of
      patients using lithium. The aim was to assess the clarity of presentation and
      applicability of monitoring instructions for patients using lithium in CPGs for
      treatment of BD. METHODS: CPGs for treatment of BD were selected from
      acknowledged professional organizations from multiple continents. CPGs were rated
      on the clarity of presentation and applicability of lithium monitoring
      instructions using the Appraisal of Guidelines Research and Evaluation (AGREE) II
      tool. The applicability of monitoring instructions was assessed according to the
      Systematic Information for Monitoring (SIM) score. Monitoring instructions were
      considered applicable when a SIM score of >=3 was found. RESULTS: The clarity of
      presentation for six out of the nine CPGs was good (>70%) using the AGREE II
      tool. Only one CPG scored >70% on applicability. Descriptions of the resource
      implications and facilitators of and barriers to monitoring were most often
      missing. All CPGs contained instructions for monitoring of lithium serum levels
      and renal and thyroid function. Information provided in monitoring instructions
      (n = 247) was in general applicable to clinical practice (77%) based on the SIM
      score. Overall, a median SIM score of 3 (interquartile range 3-4) was found.
      CONCLUSIONS: Improvement of the applicability of CPGs is recommended, and can be
      achieved by describing the resource implications and facilitators of and barriers
      to monitoring. In addition, information on critical values and instructions on
      how to respond to aberrant monitoring parameters are needed. With such
      improvements, CPGs may better aid health care professionals to monitor patients
      using lithium.

PMID- 30105768
TI  - Effect of different protocols of eugenol removal on the bond strength between the
      fibre post and root dentin.
AB  - The aim of this study was to evaluate the bond strength between the fibre post
      and root dentin after different cleaning protocols to remove eugenol from dentin.
      The residues and elemental composition of dentin were analysed using SEM and EDS.
      Bovine incisor roots were obturated with eugenol-based sealer. The post space was
      prepared, and the roots were divided into the following groups according to the
      cleaning protocol: unfilled (negative control), saline solution (positive
      control), 70% ethanol, acetone and 70% isopropyl alcohol. The fibre posts were
      cemented and push-out test realised. Chemical analysis of the dentin was
      performed using SEM and EDS. The bond strength values were analysed by
      anova/Fisher's and were as follows: negative control (7.30 +/- 2.77) = 70%
      ethanol (6.64 +/- 2.91) = 70% isopropyl alcohol (5.01 +/- 3.15) = acetone (4.42
      +/- 1.53) >positive control (1.29 +/- 0.56). It was concluded that 70% ethanol
      may be a good cleaning protocol to remove eugenol from dentin.

PMID- 30105769
TI  - Outcomes of Community-Based Suicide Prevention Approaches That Involve Reducing
      Access to Pesticides: A Systematic Literature Review.
AB  - OBJECTIVE: Pesticide ingestion is among the most commonly utilized means of
      suicide worldwide. Restricting access to pesticides at a local level is one
      strategy to address this major public health problem, but little is known about
      its effectiveness. We therefore conducted a systematic literature review to
      identify effective community-based suicide prevention approaches that involve
      restricting access to pesticides. METHOD: We searched Embase, Scopus, PsycINFO,
      Cochrane Library, CINAHL, and PubMed for well-designed studies that reported on
      suicide-related outcomes (i.e., attempted or completed suicide). RESULTS: We
      identified only five studies that met our eligibility criteria (two randomized
      controlled trials, two studies with quasi-experimental designs, and one study
      with a before-and-after design). These studies tested different interventions:
      the introduction of nonpesticide agricultural management, providing central
      storage facilities for pesticides, distributing locked storage containers to
      households, and local insecticide bans. The only sufficiently powered study
      produced no evidence of the effectiveness of providing household storage
      containers. Three interventions showed some promise in reducing pesticide
      suicides or attempts, with certain caveats. CONCLUSIONS: Our review identified
      three community interventions that show some promise for reducing pesticide
      suicides by restricting access to means, which will require replication in large,
      well-designed trials before they can be recommended.

PMID- 30105770
TI  - Evaluation of the combined use of two different respiratory monitoring systems
      for 4D CT simulation and gated treatment.
AB  - PURPOSE: Two different respiratory monitoring systems (Varian's Real-Time
      Position Management (RPM) System and Siemens' ANZAI belt Respiratory Gating
      System) are compared in the context of respiratory signals and 4D CT images that
      are accordingly reconstructed. This study aims to evaluate the feasibility of
      combined use of RPM and ANZAI systems for 4DCT simulation and gated radiotherapy
      treatment, respectively. METHODS: The RPM infrared reflecting marker and the
      ANZAI belt pressure sensor were both placed on the patient's abdomen during 4DCT
      scans. The respiratory signal collected by the two systems was synchronized.
      Fifteen patients were enrolled for respiratory signal collection and analysis.
      The discrepancies between the RPM and ANZAI traces can be characterized by phase
      shift and shape distortion. To reveal the impact of the changes in respiratory
      signals on 4D images, two sets of 4D images based on the same patient's raw data
      were reconstructed using the RPM and ANZAI data for phase sorting, respectively.
      The volume of whole lung and the position of diaphragm apex were measured and
      compared for each respiratory phase. RESULTS: The mean phase shift was measured
      as 0.2 +/- 0.1 s averaged over 15 patients. The shape of the breathing trace was
      found to be in disagreement. For all the patients, the ANZAI trace had a steeper
      falloff in exhalation than RPM. The inhalation curve, however, was matched for
      nine patients, steeper in ANZAI for five patients and steeper in RPM for one
      patient. For 4D image comparison, the difference in whole-lung volume was about 
      4% to +4% and the difference in diaphragm position was about -5 mm to +4 mm,
      compared in each individual phase and averaged over seven patients. CONCLUSIONS:
      Combined use of one system for 4D CT simulation and the other for gated treatment
      should be avoided as the resultant gating window would not fully match with each
      other due to the remarkable discrepancy in breathing traces acquired by the two
      different surrogate systems.

PMID- 30105771
TI  - Social stress-potentiated methamphetamine seeking.
AB  - Human studies of substance use disorder show that psychological stress and drug
      availability interact following rehabilitation, contributing to the high relapse
      potential. Social stressors trigger particularly strong motivation for drug, but
      how this affects neuronal function to increase relapse is unknown. Animal models,
      which allow for the dissection of neural mechanisms, primarily utilize physical
      stressors to trigger relapse. To recapitulate psychosocial post-rehabilitation
      challenges in animals, we developed a model of social stress-potentiated
      methamphetamine (METH) seeking. Rats receive a single social defeat (SD) session
      after completion of self-administration and extinction of lever pressing. While a
      reminder of the SD was insufficient to reinstate METH seeking on its own, rats
      that received a reminder of SD followed by a METH-priming injection displayed
      potentiated reinstatement over METH-priming alone. Examination of neuronal
      activation patterns of the METH-primed reinstatement session identified c-Fos
      immunoreactivity in the basolateral amygdala (BLA) as correlated with SD score, a
      measure of defeat latency. Rapidly defeated rats showed potentiated METH-primed
      reinstatement and elevated BLA c-Fos compared with controls. Conversely, rats
      that were undefeated during the social stress did not show potentiated METH
      primed reinstatement or elevated BLA c-Fos. Interestingly, inactivation of the
      BLA with baclofen/muscimol prior to the stress reminder and METH-priming
      generated a potentiation of METH seeking in the undefeated rats, suggesting the
      BLA may mediate resilience to the stressor. This model provides a tool for the
      further dissection of neural mechanisms mediating social stress-potentiated
      relapse and for the development of relapse-reducing therapeutics.

PMID- 30105772
TI  - Limited genetic structure and demographic expansion of the Brassicogethes aeneus
      populations in France and in Europe.
AB  - BACKGROUND: The pollen beetle, Brassicogethes aeneus (Fabricius, 1775), is one of
      the most significant pests of oilseed rape. To shed light on past and current
      pollen beetle demography (dispersal, population size), 12 microsatellite markers
      were developed, and population genetic diversity and structure were analysed at
      different spatial scales in France and in Europe from 433 individuals collected
      in 18 winter oilseed rape fields. RESULTS: Genetic differentiation among the
      population samples was low but was significant between the Estonian sample and
      the rest of Europe. Isolation by distance was significant only at the European
      scale. Genetic variability was similar among the 18 population samples.
      Demographic inferences suggested a recent expansion of B. aeneus population size
      over Europe, possibly corresponding to an increase in oilseed rape crop area
      during past decades. CONCLUSION: Current population size and dispersal are not
      straightforward to estimate from the distribution of genetic variability in B.
      aeneus over Europe because of the complexity of the demographic history of this
      pest. Nevertheless, because gene flow was important enough to prevent strong
      genetic differentiation at large geographical scales, the management of pollen
      beetle populations should likely be thought of at a continental Europe level. (c)
      2018 Society of Chemical Industry.

PMID- 30105774
TI  - Comprehensive review of Hepatitis B Virus-associated hepatocellular carcinoma
      research through text mining and big data analytics.
AB  - PubMed was text mined to glean insights into the role of Hepatitis B virus (HBV)
      in hepatocellular carcinoma (HCC) from the massive number of publications (9249)
      available to date. Reports from ~70 countries identified >1300 human genes
      associated with either the Core, Surface or X gene in HBV-associated HCC. One
      hundred and forty-three of these host genes, which can potentially yield 1180
      biomolecular interactions, each were reported in at least three different
      publications to be associated with the same HBV. These 143 genes function in 137
      pathways, involved mainly in the cell cycle, apoptosis, inflammation and
      signalling. Fourteen of these molecules, primarily transcriptional regulators or
      kinases, play roles in several pathways pertinent to the hallmarks of cancers.
      'Chronic' was the most frequent word used across the 9249 abstracts. A key event
      in chronic HBV infection is the integration of HBV into the host genome. The
      advent of cost-effective, next-generation sequencing technology facilitated the
      employment of big-data analytics comprehensively to characterize HBV-host
      integration within HCC patients. A total of 5331 integration events were reported
      across seven publications, with most of these integrations observed between the
      Core/X gene and the introns of genes. Nearly one-quarter of the intergenic
      integrations are within repeats, especially long interspersed nuclear elements
      (LINE) repeats. Integrations within 13 genes were each reported by at least three
      different studies. The human gene with the most HBV integrations observed is the
      TERT gene where a total of 224 integrations, primarily at its promoter and within
      the tumour tissue, were reported by six of seven publications. This unique
      review, which employs state-of-the-art text-mining and data-analytics tools,
      represents the most complete, systematic and comprehensive review of nearly all
      the publications associated with HBV-associated HCC research. It provides
      important resources to either focus future research or develop therapeutic
      strategies to target key molecules reported to play important roles in key
      pathways of HCC, through the systematic analyses of the commonly reported
      molecules associated with the various HBV genes in HCC, including information
      about the interactions amongst these commonly reported molecules, the pathways in
      which they reside as well as detailed information regarding the viral and host
      genes associated with HBV integration in HCC patients. Hence this review, which
      highlights pathways and key human genes associated with HBV in HCC, may
      facilitate the deeper elucidation of the role of HBV in hepato-carcinogenesis,
      potentially leading to timely intervention against this deadly disease.

PMID- 30105773
TI  - microRNA and mRNA profiles in nucleus accumbens underlying depression versus
      resilience in response to chronic stress.
AB  - Major depression in negative mood is presumably induced by chronic stress with
      lack of reward. However, most individuals who experience chronic stress
      demonstrate resilience. Molecular mechanisms underlying stress- induced
      depression versus resilience remain unknown, which are investigated in brain
      reward circuits. Mice were treated by chronic unpredictable mild stress (CUMS)
      for 4 weeks. The tests of sucrose preference, Y-maze, and forced swimming were
      used to identify depression-like emotion behavior or resilience. High-throughput
      sequencing was used to analyze mRNA and miRNA quantity in the nucleus accumbens
      (NAc) harvested from the mice in the groups of control, CUMS-induced depression
      (CUMS-MDD), and CUMS-resistance to identify molecular profiles of CUMS-MDD versus
      CUMS-resilience. In data analyses and comparison among three groups, 1.5-fold
      ratio in reads per kilo-base per million reads (RPKM) was set to judge
      involvements of mRNA and miRNA in CUMS, MDD, or resilience. The downregulations
      of serotonergic/dopaminergic synapses, MAPK/calcium signaling pathways, and
      morphine addiction as well as the upregulations of cAMP/PI3K-Akt signaling
      pathways and amino acid metabolism are associated with CUMS-MDD. The
      downregulations of chemokine signaling pathway, synaptic vesicle cycle, and
      nicotine addiction as well as the upregulations of calcium signaling pathway and
      tyrosine metabolism are associated with CUMS-resilience. The impairments of
      serotonergic/dopaminergic synapses and PI3K-Akt/MAPK signaling pathways in the
      NAc are associated with depression. The upregulation of these entities is
      associated with resilience. Consistent results from analyzing mRNA/miRNA and
      using different methods validate our finding and conclusion.

PMID- 30105775
TI  - Silencing of angiotensin receptor 1 interferes with angiotensin II oncogenic
      activity in endometrial cancer.
AB  - In mammalian cells, angiotensin II (AngII) binds to 2 distinct high-affinity
      plasma membrane receptors: angiotensin receptor 1 (AT1R) and angiotensin receptor
      2 (AT2R). Healthy human endometrium from women of reproductive age expresses all
      of the components of the renin-angiotensin system. Many studies suggest that
      AngII, acting via AT1R, may have a role in the development and progression of
      cancer, which changes the expression of angiogenic factors, AngII and AT1R are
      correlated with the presence of endometrial cancer (EC). The aim of the current
      study was to identify the effects of AngII on the proliferation, cell cycle
      progression, apoptosis and mobility of ISHIKAWA, MFE296 and MFE280 EC cells with
      silenced AT1R. It also examines epithelial-mesenchymal transition markers by gene
      expression analysis. The obtained results suggest that the silencing of AT1R
      expression alters the migration and invasion ability of EC cells. However, this
      silencing is not sufficient to inhibit the effects of AngII on EC cells,
      suggesting that AngII plays a more complex role in the development of EC.

PMID- 30105776
TI  - Dosimetric comparison of surface mould HDR brachytherapy with VMAT.
AB  - INTRODUCTION: The aim of this study was to investigate the dosimetric differences
      between surface mould high-dose-rate (HDR) brachytherapy and external beam
      volumetric-modulated arc therapy (VMAT) for two treatment sites. METHODS:
      Previously treated HDR brachytherapy surface mould scalp (n = 4) and lower leg (n
      = 3) treatments were retrospectively analysed. The VMAT plans were optimised
      using an additional 3-mm setup margin on the clinical target volume (CTV) of the
      previously treated HDR plans. The HDR plans were calculated and normalised using
      the TG-43 formalism and recalculated with Acuros BV (AC). RESULTS: On average,
      the mean brain and normal tissue doses were reduced by 44.8% and 27.4% for scalp
      and lower leg VMAT cases, respectively, when compared to AC calculated HDR plans.
      For VMAT plans, the average dose to a 1-mm thick skin structure deep to the
      target volume was not any lower than that in AC HDR plans. On average, the CTV
      coverage was 13.8% and 9.6% lower for scalp cases with AC dose calculation than
      with TG-43 and 8.3% and 5.3% lower for lower leg cases if 0- or 1-cm backscatter
      material was applied above the catheters, respectively. CONCLUSIONS: VMAT is a
      feasible treatment option in the case of extensive skin malignancies of the scalp
      and lower leg. Uncertainties related to delivered dose with HDR brachytherapy
      when using the TG-43 dose calculation model or possible air gaps between the
      mould and skin favour the use of VMAT. The potential soft tissue deformation
      needs to be considered if VMAT is used.

PMID- 30105777
TI  - Who owns your data? Part III challenges to academic freedom.

PMID- 30105778
TI  - Anatomic and magnetic resonance imaging features of the salivary glands in the
      dog.
AB  - The aim of the study was to describe the anatomical location and the topographic
      relationship of the major salivary glands to associated tissues in six dog
      cadavers by high-field magnetic resonance imaging (MRI) and gross anatomical
      dissections and sections. Spin-echo T1-weighted and T2-weighted magnetic
      resonance (MR) images were obtained in transverse, sagittal, and dorsal planes
      with a 1.5 T magnet. The digastric muscle, the external auditory canal, the
      eyeball, and the medial pterygoid muscle were the most consistent topographic
      landmarks for the identification of the mandibular, parotid, and zygomatic
      salivary glands, respectively. The best differentiation and contrast of the
      glands was observed in the T2-weighted images. In contrast with the osseous and
      muscular tissues, the salivary glands appeared hyperintense in greater or lesser
      measure except for the parotid gland, which displayed a hypointense signal. The
      rostral part of the monostomatic sublingual gland was precisely located between
      the tongue and the mylohyoid muscle. The best delineation between the caudal part
      of the monostomatic sublingual gland and the cranial aspect of the mandibular
      gland was observed in dorsal MRI at the level of the palate and the branches of
      the superior dental arcade. Good evaluation of the mandibular, parotid, caudal
      part of the monostomatic sublingual, zygomatic and buccal ventral glands was
      possible in sagittal MRI in close relation with the external auditory canal and
      the temporomandibular joint. The ventral buccal glands were also observed near
      the buccal vestibule as was the palatine glands within the soft palate.

PMID- 30105779
TI  - Detection and phylogenetic characterization of atypical porcine pestivirus
      strains in Hungary.
AB  - Atypical porcine pestivirus (APPV) is a recently identified RNA virus within the
      Flaviviridae family, causing congenital tremor (CT) in the piglets of infected
      sows. We have investigated 25 cases of CT from 2005, 2007, 2010 and 2016-2018,
      originating from six different farms. RT-PCR has been performed on these samples
      and all of the affected piglets were positive to APPV. Our phylogenetic analysis
      showed that Hungarian strains show a high degree of variability and are clustered
      into five distinct lineages. Four strains originating from one farm have shown
      exceptional similarity (99.9%) to an Austrian sequence, whereas another one from
      a different herd was grouped close to a Chinese strain (96.4% similarity). Our
      results suggest multiple events of introduction of the virus from various sources
      into Hungary. This is the first report of the presence and clinical relevance of
      APPV in the Hungarian pig population.

PMID- 30105780
TI  - Incorporation of a p-Phenylene Unit into the Azuliporphyrinogens Frame-Oxidation
      and Ruthenium Cluster Coordination.
AB  - A porphyrinogen macrocycle incorporating two azulenes, phenylene and thiophene
      into the framework, joined by four C(sp3 ) atoms has been obtained as a mixture
      of six isomers. They were successfully separated and characterized
      spectroscopically. The identity of two of them was confirmed by X-ray
      crystallography. One isomer was tested in reaction with [Ru3 (CO)12 ] yielding
      exclusively pi-complex with two clusters attached to azulenes. The partial
      oxidation of porphyrinogens yielded dication with two unmodified meso bridges.
      The stepwise oxidation followed by reaction with water as nucleophile afforded
      the dicationic species with two hydroxyl groups and a trication with one OH
      group. The hydroxy-dication can be reversibly transformed into hydroxy-trication
      by addition of HBF4 etherate.

PMID- 30105782
TI  - Commentary on Tonigan et al. (2018): Clarifying the evidence for the clinical and
      public health utility of Alcoholics Anonymous for dual-diagnosis patients.

PMID- 30105781
TI  - Combinatorial Fine-Tuning of GNA1 and GlmS Expression by 5'-Terminus Fusion
      Engineering Leads to Overproduction of N-Acetylglucosamine in Bacillus subtilis.
AB  - Glucosamine-6-phosphate N-acetyltransferase (GNA1) that catalyzes acetyl transfer
      from acetyl-coenzyme A to glucosamine-6-phosphate (GlcN-6P), and glutamine
      fructose-6-phosphate aminotransferase (GlmS) that catalyzes the formation of GlcN
      6P from fructose-6-phosphate (Fru-6P), are two key enzymes in Bacillus subtilis
      for the bioproduction of N-acetylglucosamine (GlcNAc), a nutraceutical that has
      various applications in healthcare. In this study, the expression of GNA1 and
      GlmS is fine-tuned by 5'-terminus fusion engineering to improve GlcNAc
      production. Specifically, the expression level of GNA1 is enhanced at the
      translational level via fusion of an epitope tag to the 5'-terminus of GNA1 gene
      and ribosome binding site (RBS) sequence engineering. Next, enhanced expression
      of GlmS is achieved at the transcriptional and translational levels by fusing an
      mRNA stabilizer to the 5'-terminus of GlmS gene. Under the control of GNA1
      (fusion with cMyc tag and with the optimum RBS M-Rm) and GlmS (fusion with mRNA
      stabilizer DeltaermC+14/7A), the GlcNAc titer and yield in the shake flask
      increase to 18.5 g L-1 and 0.37 g GlcNAc/g glucose, which are 2.9-fold and 2.3
      fold that of the control, respectively. This synthetic pathway fine-tuning method
      at the transcriptional and translational levels by combinatorial modulation of
      regulatory elements, including epitope tag, RBS sequence, and mRNA stabilizer,
      might represent a general and effective approach for the construction of
      microbial cell factories.

PMID- 30105783
TI  - Influence of lag length on repetition priming in emotional stimuli: ERP evidence.
AB  - BACKGROUND: Previous studies have demonstrated both behavioral and neural
      evidence for the potential mediations of lag length and pre-existing memory
      representation on repetition priming. However, such mediations on emotional
      stimuli have not been described. METHODS: The current experiment intended to
      disentangle lag length from pre-existing memory representation. A lexical
      decision task was performed, in which different emotional characters (either
      normal or transposed) were re-presented either immediately or delayed. RESULTS:
      In immediate repetition, one early and two late (ie, N400 and late positive
      complex) repetition-related event-related potential (ERP) effects were elicited,
      but these were not sensitive to pre-existing memory representation. The delayed
      repetition case merely observed the N400. CONCLUSION: These results suggest that
      the repetition-related priming effect is neutrally sensitive to lag length.
      Emotional information potentially exerts early and later influences in the
      processing underlying stimuli memory.

PMID- 30105784
TI  - Thermodesulfobium sp. strain 3baa, an acidophilic sulfate reducing bacterium
      forming biofilms triggered by mineral precipitation.
AB  - Sulfate reducing prokaryotes are promising candidates for the remediation of
      acidic metal-rich waste waters. However, only few acidophilic species have been
      described to date. Chemolithoautotrophic strain 3baa was isolated from sediments
      of an acidic mine pit lake. Based on its 16S-rRNA gene sequence it belongs to the
      genus Thermodesulfobium. It was identified as an acidophile growing in artificial
      pore water medium in the range of pH 2.6-6.6. Though the highest sulfate
      reduction rates were obtained at the lower end of this range, elongated cells and
      extended lag phases demonstrated acid stress. Sulfate reduction at low pH was
      accompanied by the formation of mineral precipitates strongly adhering to solid
      surfaces. A structural investigation by laser scanning microscopy, electron
      microscopy and X-ray microanalysis revealed the formation of Al hydroxides and Fe
      sulfides which were densely populated by cells. Al hydroxides precipitated first,
      enabling initial cell attachment. Colonization of solid surfaces coincided with
      increased sulfate reducing activity indicating more favourable growth conditions
      within biofilms compared with free-living cells. These findings point out the
      importance of cell-mineral interaction for biofilm formation and contribute to
      our understanding how sulfate reducing prokaryotes thrive in both natural and
      engineered systems at low pH.

PMID- 30105785
TI  - Intentional multiple mating by females in a species where sneak fertilization
      circumvents female choice for parental males.
AB  - This paper describes how individual female ocellated wrasse Symphodus ocellatus
      distribute their spawning among males and nests in space and time. It is based on
      previously collected genetic data of larvae from ten different nests (used to
      reconstruct half and full-sibling groupings both within and among nests on
      multiple days) and behavioural data of marked females across the reproductive
      season. Both the genetic analyses and behavioural observations confirm that
      female S. ocellatus intentionally engage in multiple mating, by repeatedly
      spawning at the same nest on different days and at several different nests (up to
      12 spawning events over 3 weeks), leading to mixed paternity among her young. The
      main benefit of such high and intentional multiple mating is probably insurance
      against brood failure due to nest predation, desertion or poor paternal care by
      the male. These findings reveal that even in systems where females attempt to
      avoid male-controlled mixed paternity, they may still engage in intentional
      multiple mating due to these potential benefits.

PMID- 30105786
TI  - Bi-directional modulation of cellular interactions in an in vitro co-culture
      model of tendon-to-bone interface.
AB  - OBJECTIVES: This work aimed at studying in vitro interactions between human
      tendon-derived cells (hTDCs) and pre-osteoblasts (pre-OBs) that may trigger a
      cascade of events involved in enthesis regeneration. MATERIALS AND METHODS: The
      effect of 5 osteogenic medium (OM) conditions over the modulation of hTDCs and
      pre-OBs towards the tenogenic and osteogenic phenotypes, respectively, was
      studied. Three different medium conditions were chosen for subsequently
      establishing a direct co-culture system in order to study the expression of bone,
      tendon and interface-related markers. RESULTS: A higher matrix mineralization and
      ALP activity was observed in co-cultures in the presence of OM. Higher
      transcription levels of bone- (ALPL, RUNX2, SPP1) and interface-related genes
      (ACAN, COMP) were found in co-cultures. The expression of aggrecan was influenced
      by the presence of OM and cell-cell interactions occurring in co-culture.
      CONCLUSIONS: The present work assessed both the influence of OM on cell phenotype
      modulation and the importance of co-culture models while promoting cell-cell
      interactions and the exchange of soluble factors in triggering an interface-like
      phenotype to potentially modulate enthesis regeneration.

PMID- 30105787
TI  - Quality of life before and after cosmetic procedures on the face: A cross
      sectional study in a public service.
AB  - BACKGROUND: Quality of life can be impaired by health conditions that modify body
      appearance. AIMS: The objective of this cross-sectional study was to evaluate the
      quality of life of patients before and after free-of-charge esthetic
      dermatological treatments offered in a philanthropic Dermatological Clinic for
      nonpathological conditions, such as anti-aging procedures. METHODS: All
      consecutive patients admitted between March and November 2016 were recruited. All
      esthetic treatments in this study were simple procedures applied in one session
      only, on the face, neck, arms, and upper chest, with a consult visit scheduled
      four weeks later for clinical evaluation. The WHOQOL-BREF instrument was used
      before and one month after the procedure. RESULTS: WHOQOL-BREF scores increased
      significantly after treatment (P < 0.001) in all the domains. CONCLUSION:
      Patients undergoing simple dermatological treatments applied by specialists
      report overall and specific domain improvements in quality of life, according to
      the World Health Organization instrument, regardless of the type of procedure.

PMID- 30105789
TI  - Serum exosomes of chronic gastritis patients infected with Helicobacter pylori
      mediate IL-1alpha expression via IL-6 trans-signalling in gastric epithelial
      cells.
AB  - Emerging evidence has linked the exosomes to many immunological disorders,
      including infectious diseases. However, knowledge regarding the role of exosomes
      in Helicobacter pylori infection is limited. Here, we show that serum exosomes
      from chronic gastritis patients with H. pylori infection (Hp exosomes) stimulate
      the expression of the soluble interleukin (IL)-6 receptor (sIL-6R), which is
      involved in IL-6 trans-signalling in gastric epithelial cells. Interestingly, sIL
      6R up-regulates expression of the proinflammatory cytokine IL-1alpha, and the
      neutralization of sIL-6R suppresses IL-1alpha secretion. Thus, Hp exosomes
      regulate IL-1alpha expression via sIL-6R-mediated IL-6 trans-signaling.
      Altogether, this study reveals a novel perspective in which exosomes play a vital
      role in immunological mechanisms during H. pylori infection.

PMID- 30105790
TI  - Service satisfaction and helpfulness ratings, mental health literacy and help
      seeking barriers of carers of individuals with dual disabilities.
AB  - BACKGROUND: Carer mental health literacy and help seeking are areas that are not
      well researched in the intellectual disability field. This study aimed to explore
      the above including service utilization experiences of Australian parents with an
      offspring with an intellectual disability and a comorbid psychiatric disorder.
      METHOD: Forty-one parents took part in an online survey assessing satisfaction
      and helpfulness ratings of received services. Twenty-six parents also completed
      items to assess mental health literacy and attitudinal barriers to help seeking.
      RESULTS: Parents showed good mental health literacy with depression and with
      challenging behaviour associated with autism and poorer literacy with mixed
      presentations. Few attitudinal barriers to help seeking were reported. Parents
      reported varied helpfulness and satisfaction ratings with disability and mental
      health services. CONCLUSIONS: Parents are capable of recognizing the need to seek
      professional help for their offspring. Implications for service coordination,
      provision and carer involvement are discussed.

PMID- 30105791
TI  - Optimizing the Thermoelectric Performance of Poly(3-hexylthiophene) through
      Molecular-Weight Engineering.
AB  - Poly(3-hexylthiophene) (P3HT) films with various molecular weights (MWs) were
      successfully prepared, and both their molecular structures and thermoelectric
      (TE) properties were investigated. It was found that the molecular weight of P3HT
      had an important effect on the carrier-transport properties by affecting the
      molecular structure and, as a result, also had an effect on the TE performance.
      The electrical conductivity of the P3HT films first increased upon increasing the
      molecular weight and then decreased at high molecular weights, whereas the
      Seebeck coefficient remained at the same level. As a result, the P3HT-M50k (MW~50
      000 g mol-1 ) film reached an electrical conductivity of (103.8+/-1.2) S cm,
      which is more than 20 times higher than the electrical conductivity of P3HT-M10k
      (MW~10 000 g mol-1 ) and almost 30 % higher than the electrical conductivity of
      P3HT-M100k (MW~100 000 g mol-1 ). Consequently, the maximum TE power factor of
      P3HT-M50k at room temperature was as high as (22.6+/-0.6) MUW mK-2 , which is
      much higher than that of either P3HT-M10k or P3HT-M100k . Microstructure analysis
      combined with C-AFM suggested that carrier transport between most of the ordered
      and amorphous regions was unconnected in films with low molecular weights, and
      this resulted in a high migration barrier and poor carrier mobility. Upon
      increasing the molecular weight, the long molecular chain provided enough
      connectivity for the charge to move through the ordered regions, which decreased
      the carrier barrier and increased carrier mobility. Therefore, both the
      conductivity and Seebeck coefficient were significantly improved. However, a too
      high molecular weight could cause more folding of the polymer chain, which would
      deteriorate the electrical-transport properties. The experimental results not
      only reveal the intrinsic effect of molecular weight on the electric transporting
      properties of conducting polymers but also suggest that molecular-weight
      engineering is an effective way to design and screen high-performance polymer TE
      materials.

PMID- 30105788
TI  - Protruded retinal layers within the optic nerve head neuroretinal rim.
AB  - PURPOSE: To determine the frequency with which retinal tissues other than the
      nerve fibre layer, hereafter referred to as protruded retinal layers (PRL), are a
      component of optical coherence tomography (OCT) neuroretinal rim measurements.
      METHODS: Ninety healthy (30 White, Black and Japanese, respectively) subjects
      were included in the study. A radial scan pattern (24 B-scans centred on Bruch's
      membrane opening [BMO]) was used. For each of the 48 minimum rim width (MRW)
      measurement points, we determined whether PRL were present, absent or
      indeterminate. When present, the proportion of PRL within the MRW was quantified.
      RESULTS: Protruded retinal layers were present in 503 (11.6%), absent in 3805
      (88.1%) and indeterminate in 12 (0.3%) measurement points. Overall, 69 (76.6%)
      subjects had >=1 points with PRL, with White subjects having the highest
      frequency and Japanese the lowest (29 [97%] and 18 [60%], respectively; p <
      0.01). PRL were present in one-third of points in the temporal sector, but <=5%
      in other sectors. When present, the median PRL thickness was 53.0 (interquartile
      range [IQR]: 33.0 to 78.5) MUm, representing 20.6 (IQR: 13.0 to 28.5)% of MRW.
      Globally, the median PRL thickness comprised 1.3 (IQR: 0.2 to 3.5)% of the MRW;
      however, in the temporal sector, it exceeded 30% of MRW in some subjects.
      CONCLUSIONS: Protruded retinal layers are a component of MRW measurements in most
      normal subjects, occurring in almost 12% of all measurement points analysed.
      There were racial variations in the presence of PRL and a significantly higher
      frequency of PRL in the temporal sector.

PMID- 30105792
TI  - Complications and early mortality in patients with acute promyelocytic leukemia
      treated in California.

PMID- 30105793
TI  - Combined high-dose intra-arterial and intrathecal chemotherapy for the treatment
      of a case of extraocular retinoblastoma.
AB  - Patients with retinoblastoma and central nervous system (CNS) involvement are
      rarely curable with available treatments. We designed a high-dose intra-arterial
      regimen targeting the ophthalmic artery and chiasm combined with intrathecal
      chemotherapy to treat a 4-year-old patient with retinoblastoma metastasized to
      the CNS. After three cycles of this regimen, including carboplatin, melphalan,
      and intrathecal topotecan, a partial response of the orbital tumor mass and
      chiasmatic lesion, and complete response in the cerebrospinal fluid and bone
      marrow were achieved. This new treatment strategy may be explored as a treatment
      component for patients with overt extraocular retinoblastoma and CNS
      dissemination.

PMID- 30105794
TI  - Sustained-release ruxolitinib: Findings from a phase 1 study in healthy subjects
      and a phase 2 study in patients with myelofibrosis.
AB  - Ruxolitinib is the first Janus kinase (JAK) inhibitor approved for the treatment
      of myelofibrosis, where its efficacy is often associated with cytopenia. It is
      possible that the severity of cytopenia is in part driven by Cmax . A once-daily
      sustained-release (SR) formulation of ruxolitinib was therefore developed to
      decrease the Cmax /Cmin ratio relative to twice-daily immediate-release (IR)
      ruxolitinib. An SR formulation was identified based on pharmacokinetic evaluation
      in a phase 1 study in healthy adults (N = 9). This was followed by an open-label
      phase 2 study in patients with myelofibrosis (N = 41). Ruxolitinib SR treatment
      was well tolerated with blood cell counts relatively unchanged through week 16.
      In terms of efficacy, 7 patients (17.1%) had clinical improvement and 33 (80.5%)
      had stable disease. While this study has raised the possibility of an increased
      therapeutic index for ruxolitinib via an SR formulation, further studies are
      required to validate the hypothesis.

PMID- 30105795
TI  - Overexpression of KIF20A confers malignant phenotype of lung adenocarcinoma by
      promoting cell proliferation and inhibiting apoptosis.
AB  - Increasing studies showed that kinesin family member 20A (KIF20A) was
      overexpessed in several types of cancer, and its overexpression correlated with
      the oncogenesis and prognosis of cancers. However, little is known about the role
      of KIF20A in lung adenocarcinoma (LUAD). In this study, we employed the
      bioinformatics analysis to identify the upregulation of KIF20A in LUAD, then
      verified the results in human tumor specimens and LUAD cell lines. Compared with
      normal lung tissues, a ubiquitous upregulation of KIF20A was observed in LUAD
      tissues by immunohistochemistry (IHC) as well as TCGA analysis. Higher expression
      of KIF20A was significantly associated with more advanced clinicopathological
      features and shorter overall survival (OS). Moreover, multivariate Cox regression
      analysis revealed that KIF20A was an independent prognostic factor for OS. The
      expression of KIF20A was significantly elevated in LUAD cell lines. After
      silencing KIF20A, lung cancer cell cycle arrested in G1 phase and apoptosis
      increased. The same results were observed in vivo. Thus, our study demonstrated
      that KIF20A might confer malignant phenotype to LUAD by regulating cell
      proliferation and apoptosis, providing a new potential biomarker for clinical
      treatment of LUAD.

PMID- 30105796
TI  - Wogonoside impedes the progression of acute myeloid leukemia through inhibiting
      bone marrow angiogenesis.
AB  - Decreasing bone marrow (BM) microvessel density and circulating angiogenic
      cytokine levels are promising strategies for the treatment of relapsed and
      resistant acute myeloid leukemia (AML). Previous studies have reported that
      wogonoside could inhibit the progression of AML and suppress angiogenesis in a
      solid tumor, but the correlation of these two effects was ignored. In this
      research, we determined whether wogonoside could inhibit angiogenesis in this
      hematologic malignancy. We found that wogonoside could inhibit tumor growth and
      progression, and prolong the survival of nude mice inoculated with U937/MDR.
      Besides, reducing BM angiogenesis might cause therapeutic effect against
      resistant AML. Therefore, coculture between AML cells and BM stromal cells was
      established to imitate their crosstalk. Then, the effect of wogonoside on BM
      angiogenesis was tested in vitro and in vivo. We found that wogonoside could
      suppress microvessel formation in the chicken chorioallantoic membrane assay
      model and matrigel plug assay. The mechanism research revealed that wogonoside
      could block the JAK2-STAT3 pathway in AML cells and stromal cells to break their
      positive feedback. We detected several cytokines related to AML or angiogenesis
      and found that secreted interleukin-8 was a significant angiogenic cytokine to
      induce BM angiogenesis. These findings supported that new diagnostics and
      promising treatment strategies could be developed in relapsed and resistant AML
      patients.

PMID- 30105797
TI  - miR-129 targets CDK1 and iASPP to modulate Burkitt lymphoma cell proliferation in
      a TAp63-dependent manner.
AB  - Burkitt lymphoma is one of the most common lymphatic system cancers with poor
      outcome in adult patients. p53-induced apoptosis is a critical signaling for
      preventing tumor development. Cyclin B/cyclin-dependent kinase 1 (CDK1)
      phosphorylates inhibitor of apoptosis stimulating protein of P53 (iASPP) to
      promote iASPP nucleus localization and its inhibitory effect on p53. However, p53
      is frequently mutated in Burkitt lymphoma, which gains novel oncogenic
      properties. Recently, the p53 family member, p63, became an attractive gene for
      the therapeutic strategies for patients with cancer. Therefore, we investigated
      the role of iASPP in the transactivation domain p63 (TAp63)-dependent cell
      proliferation inhibition in Burkitt lymphoma. We verified that the oncogenic
      effect of iASPP on Burkitt lymphoma is TAp63 dependent rather than p53 and
      confirmed that the interaction between CDK1 and iASPP enhanced the inhibitory
      effect of iASPP on p53 and TAp63. An online tool predicated that miR-129 might
      bind to 3'-untranslated region of iASPP and CDK1. We revealed that miR-129 acted
      as a tumor suppressor by inhibiting cancer cell proliferation and inhibiting CDK1
      and iASPP via direct binding. An miR-129 inhibitor increased nucleus iASPP and
      decreased nucleus p53 and TAp63 levels, which could be reversed by the CDK1
      knockdown, indicating that miR-129 might target CDK1 to inhibit iASPP
      phosphorylation, thus hindering iASPP nucleus localization and its inhibitory
      effect on p53 and TAp63 protein levels. Taken together, miR-129 could targetedly
      inhibit the expression of CDK1 and iASPP. CDK1 knockdown inhibits iASPP S84/S113
      phosphorylation, thus blocking iASPP nucleus localization, suppressing the
      inhibitory effect of iASPP on p53 and TAp63, and restoring TAp63-induced
      proliferation inhibition in Burkitt lymphoma cells.

PMID- 30105798
TI  - Genetic variation underlying local adaptation of diapause induction along a cline
      in a butterfly.
AB  - Diapause is a life history strategy allowing individuals to arrest development
      until favourable conditions return, and it is commonly induced by shortened day
      length that is latitude specific for local populations. Although understanding
      the evolutionary dynamics of a threshold trait like diapause induction provides
      insights into the adaptive process and adaptive potential of populations, the
      genetic mechanism of variation in photoperiodic induction of diapause is not well
      understood. Here, we investigate genetic variation underlying latitudinal
      variation in diapause induction and the selection dynamics acting upon it. Using
      a genomewide scan for divergent regions between two populations of the butterfly
      Pararge aegeria that differ strongly in their induction thresholds, we identified
      and investigated the patterns of variation in those regions. We then tested the
      association of these regions with diapause induction using between-population
      crosses, finding significant SNP associations in four genes present in two
      chromosomal regions, one with the gene period, and the other with the genes
      kinesin, carnitine O-acetyltransferase and timeless. Patterns of allele
      frequencies in these two regions in population samples along a latitudinal cline
      suggest strong selection against heterozygotes at two genes within these loci
      (period, timeless). Evidence for additional loci modifying the diapause decision
      was found in patterns of allelic change in relation to induction thresholds over
      the cline, as well as in backcross analyses. Taken together, population-specific
      adaptations of diapause induction appear to be due to a combination of alleles of
      larger and smaller effect size, consistent with an exponential distribution of
      effect sizes involved in local adaption.

PMID- 30105799
TI  - The single-domain response regulator LerC functions as a connector protein in the
      Legionella pneumophila effectors regulatory network.
AB  - The intracellular pathogen Legionella pneumophila translocates more than 300
      effector proteins into host cells during infection. The PmrAB two-component
      system (TCS) has been shown to activate the expression of a large pool of these
      effector-encoding genes (EEGs) and the LetAS TCS, as part of the LetAS-RsmYZ-CsrA
      cascade, has been shown to repress the expression of another pool of EEGs. We
      identified a single-domain response regulator (SDRR), named LerC, which functions
      as a connector protein between the PmrAB and the LetAS TCSs. The lerC gene is
      strongly activated by the PmrAB TCS and the LerC protein inhibits the activity of
      the LetAS TCS. The LerC protein specifically interacts with the HPT (histidine
      phosphotransfer) domain of LetS, leading to reduced expression of the small RNAs
      RsmY and RsmZ, which leads to a reduced expression of the pool of EEGs regulated
      by the LetAS-RsmYZ-CsrA cascade. In addition, the conserved aspartic acid located
      in the LerC receiver domain is essential for its phosphorylation and function,
      suggesting that LerC functions as a phosphate-sink of LetS. Our results
      demonstrate a new role for SDRRs as connector proteins in regulatory networks,
      suggesting that members of this widespread group of proteins might function as
      connector proteins in other bacterial regulatory networks.

PMID- 30105800
TI  - Development of a risk assessment scale predicting incident functional disability
      among older people: Japan Gerontological Evaluation Study.
AB  - AIM: The aim of the present study was to develop a risk assessment scale for
      predicting incident functional disability among older adults. METHODS: We used
      prospective cohort data from the Japan Gerontological Evaluation Study, a
      nationwide survey of 90 889 functionally independent older people collected from
      23 municipalities. The incidence of functional disability was determined from
      long-term care information obtained from municipal insurance databases. We
      constructed a Cox proportional hazards model with forward stepwise selection that
      used sex, age, and 12 of the essential items of the Public Survey of Long-Term
      Care Prevention and Needs in Spheres of Daily Life (the Needs Survey). We
      assigned a score based on the obtained non-standardized regression coefficients
      for each item and summed the scores to establish the risk assessment scale. The
      predictive validity was examined. RESULTS: The cumulative incidence of functional
      disability during the 3-year follow-up period was 9.7%. A risk assessment scale
      of 0-48 that used sex, age and the Needs Survey's 10 essential items was
      established. The area under the receiver operating characteristic curve was
      0.804, and the sensitivity and specificity were both 0.733 (cut-off 16/17). There
      was no significant intermunicipality difference in the associations between the
      total scores calculated by using the scale and the risk of new incidence (P =
      0.135). CONCLUSIONS: We developed a risk assessment scale predicting incident
      functional disability composed of 10 essential items of the Needs Survey, sex and
      age. The scale had superior predictive validity, regardless of the level of
      urbanness. Geriatr Gerontol Int 2018; 18: 1433-1438.

PMID- 30105801
TI  - Iron overload in patients with rare hereditary hemolytic anemia: Evidence-based
      suggestion on whom and how to screen.

PMID- 30105803
TI  - A common functional PIEZO1 deletion allele associates with red blood cell density
      in sickle cell disease patients.

PMID- 30105804
TI  - Crossing family histories of diabetes and cardiovascular disease leads to
      unexpected outcomes in diabetic offspring.
AB  - BACKGROUND: This study investigated the isolated and crossed effects of familial
      histories (FH) of early onset coronary heart disease (EOCHD) and type 2 diabetes
      mellitus (T2DM) on diabetic offspring. METHODS: The cardiometabolic phenotype of
      1098 T2DM patients was analyzed according to an FH of T2DM and/or EOCHD,
      including body composition, fasting insulinemia, insulin sensitivity, beta-cell
      function (BCF), lipids, lipoprotein(a), high-density lipoprotein (HDL) number and
      functionality, and micro- and macrovascular complications. RESULTS: Mean age and
      T2DM duration were 69 and 18 years, respectively; 64% of patients were male, 50%
      (n = 550) had an FH of T2DM (DM[+]), and 13% (n = 145) had an FH of EOCHD
      (EOCHD[+]). Four subgroups were generated by crossing FHs: DM[-]EOCHD[-] (44%; n
      = 487); DM[+]EOCHD[-] (42%; n = 466); DM[-]EOCHD[+] (6%; n = 61); and
      DM[+]EOCHD[+] (8%; n = 84). Microangiopathies were highest among DM[+] patients,
      whose BCF was deteriorating the fastest. More numerous/dysfunctional HDLs
      characterized EOCHD[+] patients. The greatest frequency of cardiovascular disease
      (CVD; 69%) was observed in DM[-]EOCHD[+] patients, whose lipoprotein(a) and
      insulinemia were also highest (81 nmol/L and 140 pmol/L, respectively). The
      lowest frequency of CVD (30%) was observed in DM[+]EOCHD[-] patients.
      CONCLUSIONS: Familial histories of DM and EOCHD predispose to increased
      microvascular and macrovascular risk, respectively, with hyperinsulinemia,
      lipoprotein(a), and dysfunctional HDLs standing out as mediators of the inherited
      macrovascular risk. Yet, crossing these FHs did not randomly redistribute
      vascular risk, because patients with parental T2DM had fewer macrovascular
      diseases regardless of familial EOCHD. The odds of being left-handed were
      unexpectedly greater in patients with crossed parental histories.

PMID- 30105802
TI  - Proteomics: Clinical and research applications in respiratory diseases.
AB  - The proteome is the study of the protein content of a definable component of an
      organism in biology. However, the tissue-specific expression of proteins and the
      varied post-translational modifications, splice variants and protein-protein
      complexes that may form, make the study of protein a challenging yet vital tool
      in answering many of the unanswered questions in medicine and biology to date.
      Indeed, the spatial, temporal and functional composition of proteins in the human
      body has proven difficult to elucidate for many years. Given the effect of
      microRNA and epigenetic regulation on silencing and enhancing gene transcription,
      the study of protein arguably provides more accurate information on homeostasis
      and perturbation in health and disease. There have been significant advances in
      the field of proteomics in recent years, with new technologies and platforms
      available to the research community. In this review, we briefly discuss some of
      these new technologies and developments in the context of respiratory disease. We
      also discuss the types of data science approaches to analyses and interpretation
      of the large volumes of data generated in proteomic studies. We discuss the
      application of these technologies with regard to respiratory disease and
      highlight the potential for proteomics in generating major advances in the
      understanding of respiratory pathophysiology into the future.

PMID- 30105805
TI  - Review: Current concepts in computer-assisted hip arthroscopy.
AB  - In the last 15 years, hip arthroscopy has become increasingly popular in
      addressing femoroacetabular impingement (FAI) because of its minimally invasive
      approach. However, assessing the adequacy of bone resection when correcting FAI
      can be difficult because visualisation and spatial awareness of the joint are
      poor. Recent advances in technology in the field of computer-assisted surgery and
      navigation and robotic surgery in orthopaedics as a resource for preoperative
      planning and intraoperative assistance have been widely reported. This technology
      is expected to upgrade surgical planning and operative techniques, decrease human
      error and improve patient outcomes by precisely defining the divergent anatomy
      and kinematics of the hip joint. This review attempts to bring the reader up-to
      date with the current developments in the field of computer assisted hip
      arthroscopy, and discusses our experience with pre-operative planning, navigation
      and robotics and also provides a platform for future research in this arena.

PMID- 30105806
TI  - Internal quality control status for BNP and NT-proBNP in China from 2014 to 2017.
AB  - BACKGROUND: This study aimed to investigate and analyze the status of internal
      quality control (IQC) for BNP and NT-proBNP from 2014 to 2017, so as to have an
      integral understanding of quality performance of measurement in clinical
      laboratories in China. METHODS: The 4-year IQC information for BNP and NT-proBNP
      of participant laboratories were collected through EQA reporting system.
      Percentages of laboratories meeting different quality requirements (pass rates)
      for current coefficient of variations (CVs) were calculated afterwards. Further
      analysis for current CVs and pass rates among different years and measurement
      systems were conducted. Finally, we analyzed and summarized IQC practice and its
      changes in 4 years. RESULTS: The current CVs for BNP and NT-proBNP have decreased
      significantly from 2014 to 2017, and pass rates both presented significant
      increasing trends. NT-proBNP had higher pass rates than BNP regardless of 1/3TEa
      or 1/4TEa specification was used. The main measurement systems for two analytes
      were different. For NT-proBNP, current CVs of Roche has decreased significantly
      among 4 years and were significantly lower than Radiometer and BioMerieux in
      2015. Current CVs of Abbott also had decreasing tendency for BNP. Analysis of IQC
      practice indicated that control rules and IQC frequency had made great progress
      in 4 years. CONCLUSION: The imprecision performance of measurement of BNP and NT
      proBNP has improved with decreasing of current CVs and increasing of pass rates
      in 4 years. However, it still needs continual improvement. Clinical laboratories
      in China should take active actions to promote performance of BNP and NT-proBNP
      measurement.

PMID- 30105808
TI  - Randomized controlled trial of emotionally focused couple therapy compared to
      treatment as usual for depression: Outcomes and mechanisms of change.
AB  - This randomized controlled trial examined the effectiveness of Emotionally
      Focused Therapy (EFT) for depression and relationship satisfaction versus usual
      care (i.e., couple therapy other than EFT), and explored mechanisms of change.
      Mixed model trajectory analyses of 16 couples indicated EFT was associated with
      greater improvement in relationship satisfaction among men and women. Men
      receiving EFT reported greater improvements in depressive symptoms compared to
      usual care. Unified structural equation modeling revealed changes in relationship
      satisfaction preceded changes in depressive symptoms in one cluster of partners,
      while changes in depression preceded changes in relationship satisfaction in a
      second cluster. Two other clusters reported simultaneous changes in satisfaction
      and depression. This study provides encouraging results on the effectiveness of
      EFT for depression, and insight into mechanisms of change.

PMID- 30105807
TI  - Restoration of the nasopharyngeal response after bilateral sectioning of the
      anterior ethmoidal nerve in the rat.
AB  - In response to stimulation of the nasal passages with volatile ammonia vapors,
      the nasopharyngeal reflex produces parasympathetically mediated bradycardia,
      sympathetically mediated increased peripheral vascular tone, and apnea. The
      anterior ethmoidal nerve (AEN), which innervates the anterior nasal mucosa, is
      thought to be primarily responsible for providing the sensory afferent signals
      that initiate these protective reflexes, as bilateral sectioning causes an
      attenuation of this response. However, recent evidence has shown cardiovascular
      responses to nasal stimulation with ammonia vapors are fully intact 9 days after
      bilateral AEN sectioning, and are similar to control animals without bilaterally
      sectioned AENs. To investigate this restoration of the nasopharyngeal response,
      we recorded the cardiorespiratory responses to nasal stimulation with ammonia
      vapors immediately after, and 3 and 9 days after, bilateral AEN sectioning. We
      also processed brainstem tissue for Fos to determine how the restoration of the
      nasopharyngeal response would affect the activity of neurons in the medullary
      dorsal horn (MDH), the part of the ventral spinal trigeminal nucleus caudalis
      region that receives primary afferent signals from the nose and nasal passages.
      We found 3 days after bilateral AEN sectioning the cardiorespiratory responses to
      nasal stimulation are partially restored. The bradycardic response to nasal
      stimulation is significantly more intense 3 days after AEN sectioning compared to
      Acute AEN sectioning. Surprisingly, 3 days after AEN sectioning the number of Fos
      positive neurons within MDH decreased, even though the cardiorespiratory
      responses to nasal stimulation intensified. Collectively these findings indicate
      that, besides the AEN, there are alternate sensory pathways that can activate
      neurons within the trigeminal nucleus in response to nasal stimulation. The
      findings further suggest trigeminal neuronal plasticity involving these alternate
      sensory pathways occurs in as few as 3 days after bilateral AEN sectioning.
      Finally, activation of even a significantly reduced number of MDH neurons is
      sufficient to initiate the nasopharyngeal response.

PMID- 30105809
TI  - Building the foundation for veterinary register-based epidemiology: A systematic
      approach to data quality assessment and validation.
AB  - Epidemiological studies often use data from registers. Data quality is of vital
      importance for the quality of the research. The aim of this study was to suggest
      a structured workflow to assess the quality of veterinary national registers. As
      an example of how to use the workflow, the quality of the following three
      registers was assessed: the Central Husbandry Register (CHR), the database for
      movement of pigs (DMP) and the national Danish register of drugs for veterinary
      use (VetStat). A systematic quantitative assessment was performed, with
      calculation the proportion of farms and observations with "poor quality" of data.
      "Poor" quality was defined for each measure (variable) either as a mismatch
      between and/or within registers, registrations of numbers outside the expected
      range, or unbalanced in- and outgoing movements. Interviews were conducted to
      make a complementary qualitative assessment. The proportion of farms and
      observations within each quality measure varied. This study highlights the
      importance of systematic quality assessment of register data and suggests a
      systematic approach for such assessments and validations without the use of
      primary data.

PMID- 30105810
TI  - Application of smart bracelet to monitor frailty-related gait parameters of older
      Chinese adults: A preliminary study.
AB  - AIM: Smart bracelets are popular today. Based on their built-in motion sensors,
      they can serve as a cost-effective method of gait assessment in home-based care.
      Few studies have applied smart bracelets in the gait assessment of older Chinese
      adults. The present study aimed to: (i) establish reference gait parameters of
      older Chinese adults using smart bracelets under single and dual task; and (ii)
      explore the differences in gait parameters among non-frail and pre-frail Chinese
      older adults. METHODS: A total of 50 community-dwelling older Chinese adults aged
      >=50 years wore a smart bracelet sensor in the L3 region of the back and
      underwent a 10-m walking test under single- and dual-task conditions.
      Participants were preliminarily classified into non-frail and pre-frail groups
      based on the Fatigue, Resistance, Ambulation, Illnesses and Loss of Weight scale.
      Gait parameters including average walking speed, step frequency, root mean square
      (RMS), acceleration amplitude variability, step variability, step regularity and
      step symmetry were calculated based on the data exported from the bracelet.
      RESULTS: Multivariate analysis of covariance (mancova) analysis showed that older
      adults had significantly decreased speed and step frequency (P < 0.05) under the
      dual cognitive task condition. Pre-frail older adults showed significantly
      decreased speed, mediolateral RMS, vertical RMS, anteroposterior RMS, vertical
      amplitude variability and vertical step regularity compared with non-frail older
      adults (P < 0.05). CONCLUSIONS: The present study suggested that the decline in
      gait parameters as a result of frailty could be detected by the smart bracelet
      sensor. Geriatr Gerontol Int 2018; 18: 1366-1371.

PMID- 30105811
TI  - Genetic evaluation of Atlantic salmon for growth traits incorporating SNP
      markers.
AB  - Genetic evaluations of individual fish were calculated for growth traits in North
      American Atlantic salmon with and without inclusion of genetic markers. The
      number of SNP markers was reduced to 6,000 and further to 270 in order to reduce
      the problem of overparameterization. SNP genotypes were predicted for all
      ungenotyped animals in the pedigree. Analysis of traits used a model with
      polygenic effects and SNP markers together. Polygenic effects refer to the
      additive genetic effects that remain after accounting for SNP genotypes. SNP
      marker genotypes were included as covariates to evaluate fish for growth traits
      (weight and length) in different environments (freshwater and seawater) with
      genders separated. Including regressions on SNP marker genotypes reduced the sum
      of squares of residuals by 2.7%-12.5% and increased the variability of Mendelian
      sampling effects (i.e., within-family variation) compared to traditional animal
      model evaluations. Genetic evaluations may be carried out with a few hundred
      markers which may be more affordable for genotyping large numbers of fish.

PMID- 30105812
TI  - Pathogenic genes related to the progression of actinic keratoses to cutaneous
      squamous cell carcinoma.
AB  - BACKGROUND: Actinic keratosis (AK) is an incipient form of cutaneous squamous
      cell carcinoma (cSCC). Understanding the differentially expressed genes between
      AK and cSCC states would be helpful for the early prevention and treatment of
      cSCC. Consequently, this study aimed to screen the key genes associated with the
      progression of AK to cSCC. METHODS: The microarray dataset GSE45216 was
      downloaded from the Gene Expression Omnibus, which included 10 AK and 30 primary
      cSCC skin tissue samples. Differentially expressed genes (DEGs) in cSCC samples,
      compared to those in AK, were identified. Gene co-expression relationships were
      investigated, followed by miRNA prediction. The potential functions of the co
      expressed genes were predicted by gene ontology (GO) and pathway enrichment
      analyses. In addition, the transcription factors and drug molecules,
      significantly related to the co-expressed genes, were obtained. RESULTS: A total
      of 320 DEGs were identified in the cSCC group, relative to the AK group.
      Moreover, 96 DEGs and 2,390 connecting edges were identified in the gene co
      expression network. An miRNA regulatory network was constructed, including 96
      DEGs and 16 miRNAs. In addition, three co-expression network modules were
      obtained; EIF4EBP1, SNX17, PRPF4, NXT1, and UBA5 were significant nodes in the
      modules. CONCLUSIONS: EIF4EBP1, SNX17, PRPF4, NXT1, and UBA5 may be the
      pathogenic genes contributing to the development of cSCC from AK.

PMID- 30105813
TI  - MiR-139-5p is associated with poor prognosis and regulates glycolysis by
      repressing PKM2 in gallbladder carcinoma.
AB  - OBJECTIVES: Gallbladder carcinoma (GBC) is the most highly aggressive cancer of
      biliary tract, but effective therapeutics are lacking. Emerging evidence has
      unveiled that miR-139-5p is aberrantly downregulated in cancers, including GBC.
      However, the functions and mechanisms of miR-139-5p in GBC remain unclear.
      MATERIALS AND METHODS: MiR-139-5p-overexpression was established in GBC cell
      lines, after which cell proliferation, migration, invasion, colony formation, and
      glucose metabolism were assayed in vitro. Subsequently, bioinformatics prediction
      and dual-luciferase reporter were performed to confirm that pyruvate kinase M2
      (PKM2) was a direct target of miRNA-139-5p. Xenograft mouse models were applied
      to investigate the role of miR-139-5p in GBC tumourigenicity in vivo. In situ
      hybridization and immunohistochemical assays were performed to determine the
      relationships among miR-139-5p, PKM2 expression and clinical malignancies in GBC
      samples. RESULTS: We found that miR-139-5p was substantially downregulated in GBC
      tissues. Low expression of miR-139-5p was significantly associated with poor
      clinical outcomes. GBC cell proliferation, migration, and invasion could be
      inhibited by overexpression of miR-139-5p either in vitro or in vivo. In
      addition, miR-139-5p overexpression could directly inhibit PKM2 expression and
      lead to suppression of glucose consumption, lactate production, and cellular ATP
      levels. Moreover, PKM2 was frequently upregulated in GBC and correlated with poor
      prognosis. Mechanistically, miRNA-139-5p inhibited cell proliferation, migration,
      and glycolysis in GBC, at least in part, by repressing PKM2. CONCLUSIONS: These
      results demonstrated a novel role for miR-139-5p/PKM2 in GBC progression and
      provided potential prognostic predictors for GBC patients.

PMID- 30105815
TI  - A large posterior encephalocele associated with severe ventriculomegaly,
      cerebellar atrophy and transposition of the great arteries.
AB  - Posterior encephalocele is a neural tube defect, which is a sac-like protrusion
      of the neural tissue and cerebrospinal fluid through a defect in the occipital
      bone. This embryonic anomaly may coexist with cortical dysplasia, agenesis of the
      corpus callosum, hydrocephalus, microcephaly, craniofacial abnormalities,
      ventricular and atrial septal defect. We report a case of a large posterior
      encephalocele in a fetus accompanied by unexpected major abnormalities including
      transposition of the great arteries, severe ventriculomegaly and cerebellar
      atrophy. Postnatal surgical corrections of the posterior encephalocele and then
      of the transposition of the great arteries were performed but the neonate died 2
      months after delivery.

PMID- 30105816
TI  - Combining microneedling with other minimally invasive procedures for facial
      rejuvenation: a split-face comparative study.
AB  - BACKGROUND: The introduction of minimally invasive procedures has increased
      acceptance due to their efficacy, safety, and relatively long-lasting and natural
      results. At least two different and unrelated modalities are employed to consider
      a combination treatment. OBJECTIVES: This study aims to evaluate and compare the
      use and effectiveness of combined microneedling with platelet-rich plasma (PRP)
      or trichloroacetic acid (TCA) peeling for facial rejuvenation. PATIENTS/METHODS:
      Twenty-four volunteers with photoaging were randomly divided into three equal
      groups according to performed procedure on each side of the face (microneedling
      by dermaroller alone or combined with PRP or TCA 15% peeling). They had received
      one session every 2 weeks for six sessions of treatment. Photography and punch
      biopsies were performed before and after 3 months of treatment for clinical,
      histometrical, and histological evaluation. RESULTS: Combined treatment of
      dermaroller and PRP or dermaroller and TCA showed significant improvement when
      compared with dermaroller alone. Significant increase in epidermal thickness was
      apparent in studied groups, especially after combined treatment with TCA.
      Organized collagen bundles with newly formed collagen formation and markedly
      decreased abnormal elastic fibers were noticed in the three studied groups.
      However, improvement of dermal structures was better demonstrated after combined
      treatment of Dermaroller and PRP than Dermaroller and TCA 15%. CONCLUSIONS: Most
      volunteers showed significant clinical improvement after treatment supported by
      the histometrical and histochemical evaluation; however, the combined use of
      dermaroller with PRP is apparently more beneficial for facial rejuvenation.

PMID- 30105817
TI  - JMRI Reviewer Awards.

PMID- 30105814
TI  - Inactivation of Fam20b in the neural crest-derived mesenchyme of mouse causes
      multiple craniofacial defects.
AB  - The glycosaminoglycan (GAG) chains attached to the core proteins of proteoglycans
      exert multiple roles, such as enriching signal molecules and regulating the
      binding of ligands to the corresponding receptors. A newly identified kinase -
      family with sequence similarity 20 member B (FAM20B) - is essential for the
      formation of GAG chains. The FAM20B protein phosphorylates the initial xylose on
      the side chain of a serine residue in the protein. Although the GAG chains of
      proteoglycans are believed to be indispensable during craniofacial development,
      there are few reports on their exact functions in craniofacial organogenesis. In
      this study, by mating Wnt1-cre mice with Fam20b-floxed mice (Fam20bflox/flox), we
      created Wnt1-Cre;Fam20bflox/flox mice in which Fam20b is ablated in the neural
      crest-derived mesenchyme. The Wnt1-Cre;Fam20bflox/flox mice died immediately
      after birth because of complete cleft palates. In addition to cleft palate, Wnt1
      Cre;Fam20bflox/flox mice also manifested tongue elevation, micrognathia,
      microcephaly, suture widening, and reduced mineralization in the calvaria, facial
      bones, and temporomandibular joint. These findings indicate that the
      proteoglycans formed through the catalysis of FAM20B are essential for the
      morphogenesis and mineralization of the craniofacial complex.

PMID- 30105818
TI  - Replacement of the portal vein during orthotopic liver transplantation in the
      patient with biliary atresia.

PMID- 30105819
TI  - Dietary fats modify vascular fat composition, eNOS localization within lipid
      rafts and vascular function in obesity.
AB  - We tested whether dietary fatty acids alter membrane composition shifting
      localization of signaling pathways within caveolae to determine their role in
      vascular function. Wild type (WT) and caveolin-1-deficient mice (cav-1 KO),
      required for vascular caveolae formation, were fed low fat (LF), high saturated
      fat (HF, 60% kcal from lard), or high-fat diet with 50:50 lard and n-3
      polyunsaturated fatty acid-enriched menhaden oil (MO). HF and MO increased body
      weight and fat in WT but had less effect in cav-1 KO. MO increased unsaturated
      fatty acids and the unsaturation index of aorta from WT and cav-1 KO. In LF WT
      aorta, endothelial nitric oxide synthase (eNOS) was localized to cav-1-enriched
      low-density fractions which shifted to actin-enriched high-density fractions with
      acetylcholine (ACh). HF and MO shifted eNOS to high-density fractions in WT aorta
      which was not affected by ACh. In cav-1 KO aorta, eNOS was localized in low
      density non-caveolar fractions but not shifted by ACh or diet. Inducible NOS and
      cyclooxygenase 1/2 were not localized in low-density fractions or affected by
      diet, ACh or genotype. ACh-induced dilation of gracilis arteries from HF WT was
      similar to dilation in LF but the NOS component was reduced. In WT and cav-1 KO,
      dilation to ACh was enhanced by MO through increased role for NOS and
      cyclooxygenase. We conclude that dietary fats affect vascular fatty acid
      composition and membrane localization of eNOS but the contribution of eNOS and
      cyclooxygenase in ACh-mediated vascular responses is independent of lipid rafts.

PMID- 30105821
TI  - Limited performance of MALDI-TOF for identification of fish Aeromonas isolates at
      species level.
AB  - The aim of this study was to evaluate the usefulness of the MALDI-TOF MS to
      identify 151 isolates of Aeromonas obtained mostly from diseased fish. MALDI-TOF
      MS correctly identified all isolates to the genus level but important differences
      in the percentage of isolates correctly identified depending on the species were
      observed. Considering exclusively the first identification option, Aeromonas
      bestiarum, Aeromonas hydrophila, Aeromonas salmonicida, Aeromonas veronii and
      Aeromonas sobria were the best identified with results >95%. However, considering
      the first and second identification options, the only species that showed values
      >90% was A. hydrophila. Overall, when the database was supplemented with 14 new
      spectra, the number of accurate identifications increased (41% vs. 55%) and the
      number of inconclusive identifications decreased (45% vs. 29%), but great
      differences in the success of species-level identifications were found. Species
      distinctive mass peaks were identified only for A. hydrophila and A. bestiarum
      (5003 and 7360 m/z in 95.5% and 94.1% of their isolates, respectively). This work
      demonstrates the utility of MALDI-TOF MS for Aeromonas identification to the
      genus level, but there is no consistency for the accurate identification of some
      of the most prevalent species implicated in fish disease.

PMID- 30105820
TI  - Cognitive reserve as an outcome predictor: first-episode affective versus non
      affective psychosis.
AB  - OBJECTIVE: Cognitive reserve (CR) refers to the brain's capacity to cope with
      pathology in order to minimize the symptoms. CR is associated with different
      outcomes in severe mental illness. This study aimed to analyze the impact of CR
      according to the diagnosis of first-episode affective or non-affective psychosis
      (FEP). METHOD: A total of 247 FEP patients (211 non-affective and 36 affective)
      and 205 healthy controls were enrolled. To assess CR, common proxies have been
      integrated (premorbid IQ; education-occupation; leisure activities). The groups
      were divided into high and low CR. RESULTS: In non-affective patients, those with
      high CR were older, had higher socioeconomic status (SES), shorter duration of
      untreated psychosis, and a later age of onset. They also showed greater
      performance in most cognitive domains. In affective patients, those with a
      greater CR showed a higher SES, better functioning, and greater verbal memory
      performance. CONCLUSION: CR plays a differential role in the outcome of psychoses
      according to the diagnosis. Specifically, in order to address the needs of non
      affective patients with low CR, cognitive rehabilitation treatments will need to
      be 'enriched' by adding pro-cognitive pharmacological agents or using more
      sophisticated approaches. However, a functional remediation therapy may be of
      choice for those with an affective psychosis and low CR.

PMID- 30105822
TI  - The noncoding RNA AK127244 in 2p16.3 locus: A new susceptibility region for
      neuropsychiatric disorders.
AB  - The presence of redundant copy number variants (CNVs) in groups of patients with
      neurological diseases suggests that these variants could have pathogenic effect.
      We have collected array comparative genomic hybridization (CGH) data of about
      2,500 patients affected by neurocognitive disorders and we observed that CNVs in
      2p16.3 locus were as frequent as those in 15q11.2, being both the most frequent
      unbalances in our cohort of patients. Focusing to 2p16.3 region, unbalances
      involving NRXN1 coding region have been already associated with neuropsychiatric
      disorders, although with incomplete penetrance, but little is known about CNVs
      located proximal to the gene, in the long noncoding RNA AK127244. We found that,
      in our cohort of patients with neuropsychiatric disorders, the frequency of CNVs
      involving AK127244 was comparable to that of NRXN1 gene. Patients carrying 2p16.3
      unbalances shared some common clinical characteristics regardless NRXN1 and
      AK127244 CNVs localization, suggesting that the AK127244 long noncoding RNA could
      be involved in neurocognitive disease with the same effect of NRXN1 unbalances.
      AK127244 as well as NRXN1 unbalances seem to have a particular influence on
      language development, behavior or mood, according with the topographic
      correlation between NRXN1 expression and prefrontal cortex functions.

PMID- 30105823
TI  - Phylogeography of the wild Lager-brewing ancestor (Saccharomyces eubayanus) in
      Patagonia.
AB  - Saccharomyces eubayanus is the close relative of the Lager-brewing yeast and was
      firstly found in North Patagonia associated with Nothofagus trees. In recent
      years additional strains were found in North America, Asia and New Zealand, and
      genomic analyses showed the existence of two main populations of this yeast, both
      of them present in Patagonia. Here, we performed the most comprehensive study of
      S. eubayanus in Patagonia natural environments (400 samples) and confirmed that
      this region has the highest isolation success rate for this species described
      worldwide (more than 10-fold). The genetic characterization of 200 isolates
      (COX2, DCR1, intFR) revealed five geographically structured subpopulations. We
      hypothesized that marine ingressions and glaciations, which shaped the Patagonian
      landscape, contributed on population differentiation. The first large screening
      of fermentation performance of 60 wild S. eubayanus strains indicated which
      subpopulations would be more suitable for beer production.

PMID- 30105824
TI  - A case trial study of the effect of ageing on fresh and post-thaw sperm in dogs.
AB  - The aim of this study was to compare fresh and post-thaw sperm
      morphofunctionality of young and old dogs of a case trial study. Young dogs had
      higher libido and fresh semen motility, vigour and plasmatic membrane integrity.
      Conversely, senile dogs had higher percentage of major sperm defects (proximal
      droplets). Young dogs presented higher post-thaw sperm acrosomal membrane
      integrity and lower percentage of sperm defects compared to senile dogs. In
      conclusion, senility has deleterious effect on fresh semen, causing high
      incidence of defected spermatozoa and plasma membrane lesion, decreasing sperm
      motility and vigour. Moreover, senile dogs are more susceptible to sperm
      cryodamage.

PMID- 30105825
TI  - Risk of developing radiogenic cancer following photon-beam radiotherapy for
      Graves' orbitopathy.
AB  - PURPOSE: The objective of this study was to estimate the probability for cancer
      development due to radiotherapy for Graves' orbitopathy with 6 MV x rays.
      METHODS: Orbital irradiation was simulated with the MCNP code. The radiation dose
      received by 10 out-of-field organs having a strong disposition for carcinogenesis
      was calculated with Monte Carlo methods. These dose calculations were used to
      estimate the organ-dependent lifetime attributable risk (LAR) for cancer
      induction in 30- and 50-yr-old males and females on the basis of the linear model
      suggested by the BEIR-VII report. Differential dose-volume histograms derived
      from patients' three-dimensional (3D) radiotherapy plans were employed to
      determine the organ equivalent dose (OED) of the brain which was partly exposed
      to primary radiation. The OED and the relevant LAR for brain cancer development
      were assessed with the plateau, bell-shaped and mechanistic models. The
      radiotherapy-induced cancer risks were compared with the lifetime intrinsic risk
      (LIR) values for unexposed population. RESULTS: The radiation dose range to
      organs excluded from the treatment volume was 0.1-91.0 mGy for a target dose of
      20 Gy. These peripheral organ doses increased the LIRs for cancer development of
      unexposed 30- and 50-yr-old males up to 1.0% and 0.2%, respectively. The
      corresponding elevations after radiotherapy of females were 2.0% and 0.4%. The
      use of nonlinear models gave an OED range of the brain of 482.0-562.5 mGy
      depending upon the model used for analysis and the patient's gender. The
      elevation of the LIR for developing brain malignancies after radiotherapy of 30
      yr-old males and females reached to 13.3% and 16.6%, respectively. The
      corresponding increases after orbital irradiation at the age of 50 yr were 6.7%
      and 8.3%. CONCLUSIONS: The level of the LIR increase attributable to radiation
      therapy for GO varied widely by the organ under examination and the age and
      gender of the exposed subject. This study provides the required data to quantify
      the elevation of these baseline cancer risks following orbital irradiation.

PMID- 30105826
TI  - Platelet-derived growth factor subunit B is required for tendon-bone healing
      using bone marrow-derived mesenchymal stem cells after rotator cuff repair in
      rats.
AB  - As a common cause of shoulder pain and disability, rotator cuff injury (RCI)
      represents a debilitating condition affecting an individual's quality of life.
      Although surgical repair has been shown to be somewhat effective, many patients
      may still suffer from reduced shoulder function. The aim of the current study was
      to identify a more effective mode of RCI treatment by investigating the effect of
      platelet-derived growth factor subunit B (PDGF-B) on tendon-bone healing after
      RCI repair by modifying bone marrow-derived mesenchymal stem cells (BMSCs).
      Surface markers of BMSCs were initially detected by means of flow cytometry,
      followed by establishment of the rat models and construction of the lentiviral
      vector. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide,
      Thiazolyl Blue Tetrazolium Bromide (MTT) assay, alizarin red staining, and oil
      red O staining were used to provide verification that PDGF-B was indeed capable
      of promoting BMSC viability, osteogenic and adipogenic differentiation
      capability. Furthermore, biomechanical assessment results indicated that PDGF-B
      could increase the ultimate load and stiffness of the tendon tissue. Real-time
      reverse-transcription quantitative polymerase chain reaction and Western blot
      analysis methods provided evidence suggesting that PDGF-B facilitated the
      expression of tendon-bone healing-related genes and proteins, while contrasting
      results were obtained after PDGF-B silencing. Taken together, the key findings of
      the current study provided evidence suggesting that overexpressed PDGF-B could
      act to enhance tendon-bone healing after RCI repair, thus highlighting the
      potential of the functional promotion of PDGF-B as a future RCI therapeutic
      approach.

PMID- 30105827
TI  - Motor neuron disease-like phenotype associated with anti-IgLON5 disease.

PMID- 30105828
TI  - Comparative genome-wide analysis of codon usage of different bacterial species
      infecting Oryza sativa.
AB  - Oryza sativa is vastly affected by microbial pathogen, causing blight-related
      diseases, which in turn deplete the growth and productivity of rice. In this
      study, we analyzed four bacterial rice pathogen genomes and reported on their
      codon usage that might have greater implication in mutation-related research.
      Differential codon usage indices, such as codon adaptation index (CAI), codon
      bias index (CBI), effective number of codons (ENc), relative synonymous codon
      usage (RSCU), correspondence analysis (COA), and parity plots, were applied on
      coding sequences of Pseudomonas fuscovaginae, Pseudomonas syringae, Xanthomonas
      oryzae, and Pseudomonas avenae speices. The RSCU results proposed a high
      frequency usage of CUG and CGC that codes for leucine and arginine in all of the
      species. The CBI and CAI values between the genomes range from 0.17 to 0.3 and
      from 0.26 to 0.35, respectively, indicating a direct proportionality between
      these indexes. The mean ENc value of P. avenae coding sequence showed high codon
      bias compared with other genomes. The axis I variation from COA analysis shows a
      mean value of 42.28% codon variations in these bacterial species. Correlation
      studies between axis I and ENc-GC3, along with CAI and CBI, suggested the
      presence of nucleotide bias and mutational pressure as major forces for codon
      bias within these species. Hence, certain genes with high CAI-CBI have been
      correlated for better gene expression. Our study highlights the importance of
      nucleotide biasness, mutation pressure, and natural selection in shaping protein
      coding genes in these four rice-affecting bacteria. This would further help in
      investigating the evolution of pathogenic gene families, which may direct
      research toward synthetic genes that could be suppressed or overrepresented based
      on their codon usage pattern toward pathogenicity.

PMID- 30105830
TI  - Study on the relationship between insulin growth factor 1 and liver fibrosis in
      patients with chronic hepatitis C with type 2 diabetes mellitus.
AB  - OBJECTIVE: To investigate the correlation between serum protein level of insulin
      growth factor 1 (IGF-1) and the degree of liver fibrosis in patients with chronic
      hepatitis C (CHC) combined with type 2 diabetes mellitus (T2DM). METHODS: The
      cases are divided into four groups. Then serum levels of IFG-1, alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis C virus (HCV)
      RNA, and HCV genotypes were detected simultaneously in patients with hepatitis C,
      liver stiffness measurement (LSM) was measured by transient elastography, and
      aspartate aminotransferase platelet ratio (APRI) score was determined. RESULTS:
      There was no significant difference between CHC with T2DM group and CHC group in
      diabetes family history (P > 0.05), but the difference between the two groups
      were significantly lower than that of T2DM group ( P < 0.05). The levels of
      fasting insulin and homeostatic model assessment of insulin resistance (HOMA-IR)
      in CHC group with T2DM group were significantly higher than those in the other
      two groups ( P < 0.05), while the IGF-1 RNA and the serum protein level in the
      two groups were significantly lower than those in the CHC group, and were lower
      than those in the control group ( P < 0.05). The level of serum IGF-1 was
      negatively correlated with HOMA-IR, LSM, and APRI score in CHC with T2DM group (
      r = -0.71, -0.75, and -0.69; P < 0.01). CONCLUSION: The degree of hepatic
      fibrosis in patients with CHC combined with T2DM was higher than that in non-T2DM
      patients with CHC, which was mainly related to insulin resistance (IR) induced by
      1b genotype HCV infection. IR can lead to impaired synthesis of IGF-1, and the
      degree of damage has a corresponding relationship with hepatic fibrosis.

PMID- 30105829
TI  - Cancer stem cell-like characteristics and telomerase activity of the
      nasopharyngeal carcinoma radioresistant cell line CNE-2R.
AB  - The radioresistance of nasopharyngeal carcinoma (NPC) may be related to cancer
      stem cells (CSCs), and the characteristics of CSCs may be maintained by
      telomerase activity. In this study, we explored the CSC-like characteristics and
      telomerase activity of the NPC radioresistant cell line CNE-2R. This work
      provides a foundation for future studies on stem cell-targeted therapies by
      targeting the radioresistance of NPC. The expression of stem cell-related
      genes/proteins and the hTERT gene/protein in CNE-2R and its parent radiosensitive
      cell line CNE-2 were detected using qPCR/Western Blot. Label-retaining cells
      (LRCs) were detected through immunocytochemistry, and telomerase activity was
      detected using a PCR-ELISA kit. CD133 expression was detected with flow
      cytometry. CNE-2R-CD133+ and CNE-2R-CD133- cells were separated with magnetic
      activated cell sorting. The proliferation and tumorigenesis capacities of CNE-2R
      CD133+, CNE-2R-CD133-, and CNE-2R cells were compared with a CCK-8 assay, sphere
      formation assay, and an in vivo experiment. Our results showed that the
      expression of stem cell-related genes and the hTERT gene in CNE-2R cells was
      higher than those in CNE-2 cells. Similarly, the expression of stem cell-related
      proteins and the hTERT protein in CNE-2R cells was markedly higher than those in
      CNE-2 cells. The proportion of LRCs in CNE-2R and CNE-2 cells was (3.10 +/-
      0.63%) vs (0.40 +/- 0.35%; P < 0.001), respectively. Telomerase activity in CNE
      2R cells was remarkably higher than that in CNE-2 cells. Flow cytometry suggested
      that the CD133 positive rates in CNE-2R and CNE-2 cells were (2.49 +/- 0.56%) vs
      (0.76 +/- 0.25%; P = 0.008), respectively. Meanwhile, the proliferation capacity,
      tumorigenesis capacity, and telomerase activity of CNE-2R-CD133+ cells were
      notably higher than those of CNE-2R-CD133- and CNE-2R cells. Collectively, CNE-2R
      displayed CSC-like characteristics; our results also showed that CNE-2R cells,
      especially the sorted CSCs, had high telomerase activity levels.

PMID- 30105831
TI  - Overexpression of AR-regulated lncRNA TMPO-AS1 correlates with tumor progression
      and poor prognosis in prostate cancer.
AB  - BACKGROUND: Prostate cancer (PCa) is a leading cause of death in males all over
      the world; besides, the diagnosis and therapy of it are still challenging.
      Researchers have revealed that long non-coding RNAs (lncRNAs) play important
      roles in the genesis and progression of human cancers, including PCa. METHODS:
      Bioinformatics analysis and Kaplan-Meier survival analysis were utilized to
      confirm TMPO-AS1 as a diagnostic and prognostic marker. The TMPO-AS1 levels in
      both patient tissues and PCa cell lines were determined by qRT-PCR analysis.
      Moreover, the chromatin immunoprecipitation (ChIP) assay identified that TMPO-AS1
      was a direct target of AR. The effect of overexpression or knockdown of TMPO-AS1
      on cell proliferation, migration, cell cycle, and cell apoptosis was assessed by
      using CCK-8, transwell assays, and flow cytometric analysis, respectively.
      RESULTS: Based on primary screening, we found that TMPO-AS1 could be a useful
      diagnostic and prognostic marker for PCa, whose expression was upregulated in PCa
      samples and associated with poorer prognosis. Bioinformatics predictions revealed
      TMPO-AS1 was associated with a series of biological processes involved in PCa
      progression. In PCa cells, TMPO-AS1 was predominantly localized in the cytoplasm
      and directly down-regulated by AR. Gain/loss-of-function assays showed TMPO-AS1
      overexpression increased cell proliferation by promoting cell cycle progression
      and promoted migration, but reduced apoptosis of PCa cells. In addition, TMPO-AS1
      may be a diagnostic and prognostic marker in multiple cancer types. CONCLUSIONS:
      AR-regulated lncRNA TMPO-AS1 functioned as an oncogenic lncRNA in PCa, and may be
      a potential diagnostic and prognostic biomarker to be used as a therapeutic
      target for PCa.

PMID- 30105832
TI  - Physical contact between mesenchymal stem cells and endothelial precursors
      induces distinct signatures with relevance to the very early phase of
      regeneration.
AB  - Multipotent adult stem cells/precursor cells, especially of the mesenchymal and
      endothelial lineage, may have great potential for bone tissue engineering.
      Although their potential is highly recognized, not much is known about the
      underlying molecular mechanisms that initiate the regeneration process, connect
      osteogenesis, and angiogenesis and, finally, orchestrate renewal of bone tissue.
      Our study addressed these questions by generating two in vitro cell culture
      models to examine the changes in the global gene expression patterns of
      endothelial precursor cells and mesenchymal stem cells after 24 hours of either
      humoral (conditioned medium) or direct cell-cell interaction (co-culture).
      Endothelial precursor cells were isolated from human buffy coat and mesenchymal
      stem cells from the bone marrow of the femoral head. The comparison of the
      treated and control cells by microarray analyses revealed in total more than 1500
      regulated genes, which were analyzed for their affiliation to angiogenesis and
      osteogenesis. Expression array analyses at the RNA and protein level revealed
      data with respect to regulated genes, pathways and targets that may represent a
      valid basis for further dissection of the systems biology of regeneration
      processes. It may also be helpful for the reconstitution of the natural
      composition of a regenerative microenvironment when targeting tissue regeneration
      both in vitro and in situ.

PMID- 30105833
TI  - "Cavernous sinus syndrome" or "middle cranial fossa syndrome": Considerations on
      terminology.

PMID- 30105834
TI  - Estimates of Horizontal Groundwater Flow Velocities in Boreholes.
AB  - Currently, monitoring tools can be deployed in observation boreholes to better
      assess groundwater flow, flux of dissolved contaminants and their mass discharge
      in an aquifer. The relationship between horizontal water velocity in observation
      boreholes and Darcy fluxes in the surrounding aquifer has been studied for
      natural flow conditions (i.e., no pumping). Interpretation of measurements taken
      with dilution tests, the colloidal borescope, the Heat Pulse Flowmeter, and other
      techniques require the conversion of observed borehole velocity u to aquifer
      Darcy flux qinfinity . This conversion is typically done through a
      proportionality factor alpha = u/qinfinity . In experimental studies as well as
      in theoretical developments, reported values of alpha vary almost three orders of
      magnitude (from 0.5 to 10). This large variability in reported values of alpha
      could be explained by: (1) unclear distinction between Darcy flux and water
      seepage velocity, (2) unclear definition of water velocity in the borehole, (3)
      effects of well screen and the presence of the measurement device itself on the
      observable velocities, and (4) hydraulic conditions in the borehole annulus. We
      address (1), (2) from a conceptual/theoretical perspective, and (3) by means of
      numerical simulations. We show that issue (1) in low porosity aquifers can yield
      to order-of-magnitude discrepancies in estimates of qinfinity ; (2) may result in
      discrepancies of up to 50%, and (3) can cause differences up to 20% of water
      velocity in the borehole void space compared to the theoretical case of an open
      borehole.

PMID- 30105836
TI  - Lubrication during root canal treatment.
AB  - Lubrication is involved in all root canal treatment phases, from dental dam
      placement to canal obturation. Most often associated with instrumentation,
      lubrication is required to facilitate the mechanical action of hand/rotary files
      and to help emulsify and suspend the debris produced. Aqueous irrigation
      solutions such as sodium hypochlorite and ethylenediaminetetraacetic acid (EDTA)
      should be regarded as lubricants, but paste-type substances are marketed
      specifically for this purpose. As more patients demand the retention of
      challenging teeth with narrow and curved root canals, the importance of
      lubrication in all aspects of root canal treatment must be acknowledged.

PMID- 30105835
TI  - Antimicrobial efficacy of 0.5% peracetic acid and EDTA with passive ultrasonic or
      manual agitation in an Enterococcus faecalis biofilm model.
AB  - We compared the antimicrobial efficacy of EDTA and 0.5% peracetic acid (PAA),
      with manual agitation (MA) or passive ultrasonic irrigation (PUI) in an
      Enterococcus faecalis biofilm model. Fifty-five single-rooted human premolar
      teeth were chemo-mechanically prepared and inoculated with E. faecalis for
      biofilm formation. These were divided into five groups (n = 11): saline solution,
      PAA+MA, PAA+PUI, EDTA+MA and EDTA+PUI. Root canal sampling and scanning electron
      microscopy of the canal lumen and dentinal tubule areas at the different root
      thirds were performed. The images were ranked based on contamination level. Only
      the PAA groups presented with no bacterial growth, with the remaining groups not
      presenting significant differences among them. PAA+PUI presented with the highest
      median position rankings in every third and location, whereas EDTA+MA performed
      similarly to the saline control. No differences were found when comparing MA and
      PUI within the same solution, however, PUI was associated with lower
      contamination levels mean rankings.

PMID- 30105837
TI  - Highly responsive fluorescent assemblies allow unique, multiparametric sensing of
      phospholipid membrane environment.
AB  - Despite decades-long extensive research, probes that provide a comprehensive
      description of the lipid membrane microenvironment are still lacking. We report
      here a 'smart' pyrene-terpyridine probe for multiparametric sensing of lipid
      membranes; wherein the complexity of the local microenvironment can be described
      by distinct features of the probe fluorescence. The self-assembly of the probe
      molecules in phospholipid bilayers is sensitive to membrane order and phase
      state. The self-assembled probes show a unique emission, influenced by dye-dye
      interactions and excited state charge transfer. Moreover, this emission is
      sensitive to interfacial hydration, with very specific changes in emission
      wavelengths and fluorescence lifetimes as lipid compositions and properties are
      varied. In parallel, changes in lipid order along with hydration affect the
      ground state interactions in dye-aggregates and thus can be measured through
      ratiometric changes in excitation and emission readouts. In addition,
      fluorescence anisotropy measurements provide another way to study the nature of
      dye-aggregates in lipid bilayers. Overall, here we demonstrate how multiple
      aspects of membrane microenvironment can be sensed through unique fluorescence
      signatures of this ?smart? probe in lipid membranes, and establish a new paradigm
      in lipid membrane sensing.

PMID- 30105838
TI  - MASS-FIX may allow identification of patients at risk for light chain amyloidosis
      before the onset of symptoms.

PMID- 30105839
TI  - Water-jet outer sheath with braided shape memory polymer tubes for upper
      gastrointestinal tract screening.
AB  - BACKGROUND: Flexible endoscopes have become an important tool for the diagnosis
      and treatment of gastric cancer. However, there are several limitations to the
      use of endoscopes in rural areas, including their high cost, poor portability,
      and unstable platform. METHODS: This paper presents a novel low-cost outer sheath
      for stomach screening. The sheath uses braided shape memory polymer (SMP) tubes
      with a water-jet to control the stiffness and bending motion. The insertion part
      of the prototype is 250 mm long with a maximum outer diameter of 16 mm and
      incorporates an internal charge-coupled device camera. RESULTS: We have tested
      the workspace and stiffness of the outer sheath. The prototype has also been
      validated with phantom and ex vivo porcine stomach experiments. CONCLUSIONS: By
      controlling the water-jet and temperature of the braided SMP tubes, the outer
      sheath achieves a large workspace and a remarkable variability in stiffness,
      demonstrating the potential clinical value of the outer sheath system.

PMID- 30105840
TI  - The early ontogeny of carapace armoring in hawksbill sea turtles (Eretmochelys
      imbricata), with comparisons to its close relatives (Loggerhead, Caretta caretta;
      Kemp's ridley, Lepidochelys kempii).
AB  - In this study, we compare and contrast armoring strategies during early ontogeny
      among three related species of marine turtles: the hawksbill, a species that
      diverged about 29 mya from the loggerhead and Kemp's ridley, which diverged from
      one another about 16 mya. Our purpose was to determine whether there was a
      correlation between divergence time and the evolution of unique morphological
      armoring specializations among these species. To find out, we completed a more
      detailed analysis of shell morphology for all of the species that revealed the
      following patterns. First, each species has evolved a somewhat different armoring
      strategy, suggesting that shell morphological evolution is surprisingly flexible.
      Second, hawksbills possess armoring features that are unique among all marine
      turtle species, suggesting a correlation between divergence through time and
      divergence in morphology. However, hawksbills also frequent coral reefs and
      selection pressures promoting their survival in those habitats may also have
      shaped their unique morphology. In contrast, loggerhead and Kemp's ridley turtles
      share similar armoring features that differ primarily in when during ontogeny
      they appear and in their degree of expression. Third, the armoring adaptations
      shown generally by juvenile marine turtles resemble those found among marine
      fishes of comparable size, probably because both small turtles and fishes are
      exposed to similar predators that promote evolutionarily similar adaptations.

PMID- 30105841
TI  - Experimental and theoretical study on structure and spectroscopic properties of 2
      bromo-3-N-(N',N'-dimethylformamidino) benzanthrone.
AB  - The goal of present research is a theoretical and experimental investigation of
      geometrical structure, electronic properties, absorption and fluorescence spectra
      prediction for 2-bromo-3-N-(N',N'-dimethylformamidino)benzanthrone. As a result
      of conformational analysis, two rotamers have been found with a rotational
      barrier of 5.45 kcal/mol. Absorption and fluorescence spectra maxima in the
      solvent (ethanol) have been calculated using the concepts of the Jablonsky
      diagram. The obtained values of the absorption and fluorescence maxima (437 and
      679 nm, respectively) correspond to the experimental values (447 and 659 nm). The
      abnormally large Stokes shift is associated with the redistribution of electron
      density, as well as flattening of the structure of the molecule in the excited
      state. According to the frontal molecular orbital analysis data, the peak in the
      long-wave part of the absorption spectra is created by an electron transition
      from the highest occupied molecular orbital (HOMO) to the lowest occupied
      molecular orbital (LUMO) (pi->pi*). Substitute group does not participate in the
      formation of absorption and fluorescence spectra.

PMID- 30105842
TI  - Costimulatory checkpoint SLAMF8 is an independent prognosis factor in glioma.
AB  - AIMS: Immune checkpoint blockade has made breakthroughs in immunotherapy for
      glioma. However, current immunotherapy has therapeutic benefits only in a subset
      of patients and accompanied by immune-related side effects. SLAMF8 is a
      costimulatory molecule that affects the activation of macrophages in
      inflammation. The study of SLAMF8 may provide new information for immunological
      research and treatment of glioma. METHODS: CGGA and TCGA cohorts of 946 patients
      with RNA sequencing data and full clinical information were analyzed using R
      language and GraphPad Prism 7. RESULTS: SLAMF8 was overexpressed along with
      malignancy progression and was a biomarker of mesenchymal subtype. As an
      independent prognostic factor, high SLAMF8 conferred reduced overall survival and
      chemotherapy resistance. SLAMF8 implied lower proportion of cancer cells along
      with increasing enrichment of monocytic lineage, myeloid dendritic cells.
      Functional analysis showed higher SLAMF8 indicated activation of antigen
      processing and presenting and the IFN-gamma/TNF/TLR-mediated signaling.
      Meanwhile, coexpressing with classical checkpoint SLAMF8 aggravated
      immunosuppression and enhanced inflammation response. CONCLUSION: Our study
      highlighted the important role of SLAMF8 in malignancy progression, shortened
      survival, and immune disorders. Further research on SLAMF8 in immunosuppression
      and inflammation response to glioma cells could aid immunotherapy for glioma.

PMID- 30105845
TI  - Association of neutrophil-to-lymphocyte ratio and natural killer cell activity
      revealed by measurement of interferon-gamma levels in a healthy population.
AB  - BACKGROUND: While a method of assaying natural killer (NK) cell activity by
      measuring the amount of interferon (IFN)-gamma released from NK cells has been
      proposed, no data are available about the factors that influence IFN-gamma levels
      related to NK cell activity. NLR has recently been reported to be a predictor of
      several diseases. In the present study, we investigated the pre-analytical
      variables for NK cell activity using measurements of IFN-gamma and the
      relationship between NLR and NK cell activity. METHODS: The NK cell activity was
      assessed with the measurement of IFN-gamma after stimulation with an NK cell
      specific stimulant (NK VueTM , ATgen, Sungnam, Korea). One hundred and six adult
      volunteers were recruited and analysis of their complete blood count data and
      serum C-reactive protein was done. Blood sample from 59 of the participants was
      also used for analysis of lymphocyte subpopulations. RESULT: Natural killer cell
      activity varied widely (range, 44.2-1775.6 pg/mL). NK cell activity was higher in
      females than in males (P = 0.014). NK cell activity decreased with increasing NLR
      (P = 0.004, r = -0.32) but NK cell activity showed no significant association
      with NK cell count or other lymphocyte subpopulations. NK cell activity levels
      according to CRP quartile were significantly different (P = 0.025). CONCLUSION:
      We have observed that NK cell activity when assessed by IFN-gamma level
      measurement was negatively correlating with NLR. This result can be helpful in
      interpreting or predicting NK cell activity in the clinical environment.

PMID- 30105843
TI  - Effect of two recombinant Trichinella spiralis serine protease inhibitors on TNBS
      induced experimental colitis of mice.
AB  - Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's
      disease (CD), is a chronic autoimmune disease. Parasitic infections and their
      products have been shown to have protective effects on autoimmune diseases,
      including IBD. In this experiment, 96 male BALB/c mice aged 6-8 weeks were
      divided randomly into two large groups: prevention and therapy. The changes in
      the various indicators of colitis were detected to demonstrate that Trichinella
      spiralis serine protease inhibitors can relieve the inflammatory severity of
      2,4,6-trinitrobenzenesulphonic acid solution (TNBS)-induced colitis and to
      explore possible immunological mechanisms. Results showed that the disease
      activity index (DAI) score, myeloperoxidase (MPO) activity, macroscopic and
      microscopic damage degrees of colon all decreased significantly, interferon (IFN)
      gamma expression decreased, interleukin (IL)-4 expression increased, nuclear
      factor kappa B (NF)-kappaB expression decreased and the percentage of CD4+ CD25+
      forkhead box protein 3 (FoxP3+ ) regulatory T cells (Treg ) cells in the spleen.
      MLN increased significantly compared to the phosphate-buffered saline (PBS)/2,4,6
      trinitrobenzenesulphonic acid solution (TNB) group. We found the same results
      with the T. spiralis Kazal-type serine protease inhibitors (TsKaSPI)+TNBS and
      TsAdSPI+TNBS groups in the large prevention group and the large therapy group,
      compared to the TNBS+PBS group with the TNBS+TsKaSPI and TNBS+TsAdSPI groups.
      Immunization with TsKaSPI and TsAdSPI on the CD models showed an intervention
      effect, possibly because TsKaSPI and TsAdSPI induced a T helper type 2 (Th2)-type
      immune response and balanced the TNBS-induced Th1-type immune response.

PMID- 30105844
TI  - A multimodality work-up of patients with Hypereosinophilia.
AB  - The work-up of patients with hypereosinophilia (HE) is complex. Following the
      recently revised World Health Organization criteria, we retrospectively reviewed
      125 patients who were referred to us to exclude a neoplastic cause of HE (2003
      2016). The clinical laboratory work-up confirmed secondary HE in 25 (20%)
      patients; myeloid/lymphoid neoplasms with rearrangements of PDGFRA (n = 9) or
      PDGFRB (n = 2) (9%); HE associated with a well-defined myeloid neoplasm in 8
      (6%); and abnormal bone marrow and/or molecular genetic abnormalities consistent
      with chronic eosinophilic leukemia (CEL), not otherwise specified (NOS) in 21
      (17%) patients. For the remaining 60 (48%) patients, a specific diagnosis was not
      identified, and 56 patients had HE related findings consistent with idiopathic
      hypereosinophilic syndrome (HES), while 4 patients who were asymptomatic. With a
      median follow up of 35.3 months (range, <1-104), patients with CEL, not otherwise
      specified (NOS) had a median OS of 26.1 months, significantly inferior to
      patients with idiopathic HES (not reached, P < .01). Thus, our experience in a
      single tertiary cancer center shows that the work-up of HE following WHO
      recommendations requires a multimodality-based approach; and a correct diagnosis
      determines risk stratification and proper patient management. However, the causes
      of HE remain unknown in approximately half of referred patients, indicating the
      need for further studies.

PMID- 30105846
TI  - Simultaneous cell traction and growth measurements using light.
AB  - Characterizing the effects of force fields generated by cells on proliferation,
      migration and differentiation processes is challenging due to limited
      availability of nondestructive imaging modalities. Here, we integrate a new real
      time traction stress imaging modality, Hilbert phase dynamometry (HPD), with
      spatial light interference microscopy (SLIM) for simultaneous monitoring of cell
      growth during differentiation processes. HPD uses holographic principles to
      extract displacement fields from chemically patterned fluorescent grid on
      deformable substrates. This is converted into forces by solving an elasticity
      inverse problem. Since HPD uses the epi-fluorescence channel of an inverted
      microscope, cellular behavior can be concurrently studied in transmission with
      SLIM. We studied the differentiation of mesenchymal stem cells (MSCs) and found
      that cells undergoing osteogenesis and adipogenesis exerted larger and more
      dynamic stresses than their precursors, with MSCs developing the smallest forces
      and growth rates. Thus, we develop a powerful means to study mechanotransduction
      during dynamic processes where the matrix provides context to guide cells toward
      a physiological or pathological outcome.

PMID- 30105847
TI  - Comparison of therapeutic effects of conventional and liposomal form of 4%
      topical hydroquinone in patients with melasma.
AB  - BACKGROUND: Melasma is a common acquired hyperpigmentation disorder observed
      mainly in young women. Hydroquinone is the basic treatment that its effect alone
      and in combination with other medications has been proven. Liposomes are
      microscopic vesicles in which water and lipid-soluble medications can be
      introduced to enhance their efficacy and specificity. The aim of this study was
      to compare therapeutic effects of topical liposomal hydroquinone with its
      conventional form on melasma. METHODS: This double-blind randomized clinical
      trial study was conducted on 20 women. Participants were asked to apply a certain
      amount of topical liposomal hydroquinone on one side of the face and conventional
      hydroquinone on the other side for three months. Skin pigmentation severity was
      measured using Melasma Area and Severity Index (MASI) at each visit, separately
      for each side of the face every month until one month after the last treatment,
      the data were recorded in a questionnaire and were analyzed by SPSS 16 software,
      paired sample t test, and repeated measurement ANOVA. RESULTS: MASI score in both
      case and control groups significantly reduced (P < 0.001) but no significant
      difference between the case and control groups was observed at any time interval
      (P > 0.05). CONCLUSION: This study shows that liposomal hydroquinone has a
      significant therapeutic effect on melasma, but we did not observe any superiority
      in comparison with the conventional method. Therefore, it can be considered in
      the treatment protocol of this disease.

PMID- 30105848
TI  - Water-Deactivated Polyelectrolyte Hydrogel Electrolytes for Flexible High-Voltage
      Supercapacitors.
AB  - With the boom of flexible electronic products and wearable devices, flexible
      energy storage devices, for example, supercapacitors with high performance, are
      attracting increasing interest. A flexible water-deactivated polyelectrolyte
      hydrogel electrolyte with good mechanical properties and high ionic conductivity
      was prepared by using an anionic polymer, carboxy methyl cellulose, and a
      cationic monomer, methacrylamidopropyltrimethyl ammonium chloride. It was then
      applied in a supercapacitor with flexible activated carbon electrodes. This
      flexible supercapacitor possesses a high operating voltage of 2.1 V owing to the
      low electrochemical activity for water within the hydrogel as a result of the
      'molecular cages' effect and hydrophilic interactions between functional groups
      and surrounding water molecules. Furthermore, this supercapacitor exhibits good
      flexibility and tailorability. As the first example of water-deactivated
      polyelectrolyte hydrogel electrolytes in applications involving flexible high
      voltage supercapacitors, this work provides a platform for the design of energy
      storage devices with high energy density for flexible and wearable electronic
      devices.

PMID- 30105850
TI  - Long noncoding RNA HOTAIR promotes renal cell carcinoma malignancy through alpha
      2, 8-sialyltransferase 4 by sponging microRNA-124.
AB  - OBJECTIVES: Accumulating evidence demonstrated that the long noncoding RNA
      (lncRNA) HOTAIR (Hox transcript antisense intergenic RNA) plays key role in renal
      cell carcinoma (RCC) malignancy, while microRNA-124 (miR-124) is a tumour
      suppressor in RCC. The aim of this work was to assess the biological function of
      HOTAIR and to explore underlying mechanism involved in HOTAIR/miR-124/alpha-2, 8
      sialyltransferase 4 (ST8SIA4) axis-regulated progression in RCC. MATERIALS AND
      METHODS: Real-time PCR analyses and western blots were performed to the levels of
      HOTAIR, miR-124 and ST8SIA4 expression in human RCC tissues and RCC cell lines
      (ACHN and 786-O). Bioinformatics analysis and dual-luciferase reporter assay were
      used to illustrate relationship between HOTAIR and miR-124 in RCC. Colony
      formation assays, EdU assays, Ki67 assays and apoptosis assays were taken to
      evaluate cell proliferation. Tumour xenograft was created to explore the
      functions of HOTAIR and ST8SIA4 in tumorigenesis in vivo. Migration assays,
      invasion assays and cell adhesion assays and were also taken to analyse the
      carcinoma progression. RESULTS: In this study, HOTAIR level was confirmed to be
      significantly upregulated in RCC samples and RCC cell lines compared with those
      in the paired adjacent tissues and normal renal cell line. Overexpression of
      HOTAIR promoted the capability of proliferation, migration and invasion in RCC
      cell lines. HOTAIR directly bound to miR-124, while miR-124 mediated the
      expression of ST8SIA4 in RCC cell lines. ST8SIA4 was upregulated in RCC tissues
      and RCC cell lines. Ectopic expression of ST8SIA4 modulated the proliferation,
      migration and invasion of RCC cells. Further results indicated that HOTAIR
      promoted the proliferation and metastasis as a competing endogenous RNA to
      regulate ST8SIA4 expression by sponging miR-124 in RCC. CONCLUSIONS: Our results
      demonstrated that HOTAIR mediated RCC progression in part through miR-124/ST8SIA4
      axis, which functioned as a new prognostic biomarker in RCC.

PMID- 30105849
TI  - D-dimer level in liver transplant recipients on the first day after surgery is
      correlated with postoperative thrombosis recurrence.
AB  - OBJECTIVE: This study aimed to investigate the relationship between plasma D
      dimer level, preoperative complications, and thrombosis in liver transplant
      recipients. METHODS: The clinical data of 525 liver transplant recipients with
      end-stage liver disease (ESLD) in the First Affiliated Hospital of Zhejiang
      University from October 2012 to December 2015 were retrospectively analyzed. The
      patients were grouped based on thrombosis before and after surgery to determine
      the risk factors for postoperative thrombosis recurrence. RESULTS: Of the
      preoperative complications assessed, esophageal varices and thrombosis were
      significantly correlated (P = 0.000); ascites, spontaneous bacterial peritonitis,
      and hepatic encephalopathy were significantly correlated with preoperative D
      dimer level (P < 0.001, P < 0.001, and P = 0.002, respectively); during the first
      week after surgery, the D-dimer level was significantly and consecutively higher
      than that before surgery and was significantly higher in the group with both
      preoperative and postoperative thrombosis than in the other groups on the first
      day after surgery (P < 0.001); the area under the curve (AUC) for diagnosis of
      postoperative thrombosis recurrence in the preoperative thrombosis group using
      plasma D-dimer level on the first day after surgery was 0.698 (P = 0.001); Cox
      regression analysis showed that D-dimer was an independent risk factor for
      postoperative thrombosis recurrence (HR = 3.062, P = 0.029). CONCLUSION: D-dimer
      level on the first day after liver transplant is related to thrombosis recurrence
      and is an independent risk factor for postoperative thrombosis recurrence.

PMID- 30105851
TI  - Cognitive performance in DSWPD patients upon awakening from habitual sleep
      compared with forced conventional sleep.
AB  - Difficult early morning awakening is one of the defining symptoms of delayed
      sleep-wake phase disorder. It is accompanied by low cognitive arousal and
      drowsiness resulting in difficulty concentrating and focusing attention upon
      awakening. We designed the current study to quantitate cognitive performance
      (i.e. omissions, commissions, reaction time [average and variability]) and
      cognitive domains (i.e. focused attention, sustained attention, impulsivity and
      vigilance) with Conners' Continuous Performance Test II during both habitual and
      conventional (00:00-07:00 hr) sleep-wake schedule in young adult patients with
      delayed sleep-wake phase disorder (n = 20, mean age = 24.8 years, SD = 3.0) and
      controls (n = 16, mean age = 24.4 years, SD = 3.4). Conners' Continuous
      Performance Test II was administered after awakening and in the afternoon during
      both habitual and conventional conditions. In-laboratory polysomnography was
      performed for 2 nights. We assessed sleep, tiredness, chronotype and depression
      using questionnaires. Saliva was sampled for dim light melatonin onset
      measurements. Repeated-measures ANOVAs were applied for the Conners' Continuous
      Performance Test II measures with group (patient/control), time
      (afternoon/morning) and condition (habitual/conventional schedule) as fixed
      factors. Patients with delayed sleep-wake phase disorder had reduced reaction
      times, especially in the morning, greater response speed variability, and made
      more omission and commission errors compared with controls. Patients with delayed
      sleep-wake phase disorder also had reduced focused attention, especially upon
      forced early awakening. The short total sleep time of patients with delayed sleep
      wake phase disorder could not statistically explain this outcome. In conclusion,
      we observed a state-dependent reduced ability to focus attention upon early
      morning awakening in patients with delayed sleep-wake phase disorder. Patients
      also had more omissions, longer reaction time and increased RT variability after
      habitual sleep, suggesting a possible small cognitive trait dysfunction in
      delayed sleep-wake phase disorder.

PMID- 30105852
TI  - Ecosystem change and zoonoses in the Anthropocene.
AB  - Changes in land use, animal populations and climate, primarily due to increasing
      human populations, drive the emergence of zoonoses. Force of infection (FOI),
      which for these diseases is a measure of the ease with which a pathogen reaches
      the human population, can change with specific zoonoses and context. Here, we
      outline three ecosystem categories-domestic, peridomestic and sylvatic, where
      disease ecology alters the FOI of specific zoonoses. Human intervention is an
      overriding effect in the emergence of zoonoses; therefore, we need to understand
      the disease ecology and other influencing factors of pathogens and parasites that
      are likely to interact differently within ecological and cultural contexts.
      Planning for One Health and community ecology, such as an ecological impact
      assessment, is required to prepare and manage the emergence and impact of
      zoonoses in the Anthropocene.

PMID- 30105853
TI  - Serum albumin or body mass index: Which prognostic factor for survival in
      patients with acute myeloblastic leukaemia?
AB  - Obesity has been associated with an increased risk of developing acute
      myeloblastic leukaemia (AML). The outcome of AML patients could thus be dependent
      on their nutritional status that can be evaluated by the simple measurement of
      serum albumin (SA) and body mass index (BMI). These two parameters could have a
      value as prognostic factors to guide patients' management. We evaluated the
      association between SA levels, BMI, and survival, evaluated as overall survival
      (OS) and event-free survival. Furthermore, we investigated the association
      between BMI, SA, and other prognostic factors of interest in AML. This
      retrospective single-center study included 159 patients diagnosed with AML at
      Nancy Hospital between 2005 and 2013, treated with aracytine and anthracycline.
      Forty-four percent of patients presented with normal weight while 56% were
      obese/overweight. Serum albumin levels were <30 g/L for 49 patients, and >=30 g/L
      for 110. Thirty-four patients with low SA levels were also obese. Favourable OS
      was associated with SA levels >=30 g/L (HR = 0.467; 95% CI 0.230-0.946; P = .034)
      but was not impacted by the BMI. Serum albumin levels appear to be an independent
      prognostic factor in AML and a better parameter than BMI for evaluating the
      nutritional status of patients at diagnosis.

PMID- 30105854
TI  - Developmental patterns of change in the influence of safe and risky peer choices
      on risky decision-making.
AB  - Adolescents take more risks when peers monitor their behavior. However, it is
      largely unknown how different types of peer influence affect adolescent decision
      making. In this study, we investigate how information about previous choices of
      peers differentially influences decision-making in adolescence and young
      adulthood. Participants (N = 99, age range 12-22) completed an economic choice
      task in which choice options were systematically varied on levels of risk and
      ambiguity. On each trial, participants selected between a safer choice (low
      variability in outcome) and a riskier choice (high variability in outcome).
      Participants made choices in three conditions: a solo condition in which they
      made choices with no additional information, a social condition in which they saw
      choices of supposed peers, and a computer condition in which they saw choices of
      a computer. Results showed that participants' choices conform to the choices made
      by the peers, but not a computer. Furthermore, when peers chose the safe option,
      late adolescents were especially likely to make a safe choice. Conversely, when
      the peer made a risky choice, late adolescents were least likely to follow
      choices made by the peer. We did not find evidence for differential influence of
      social information on decisions depending on their level of risk and ambiguity.
      These results show that information about previous decisions of peers are a
      powerful modifier for behavior and that the effect of peers on adolescents'
      decisions is less ubiquitous and more specific than previously assumed.

PMID- 30105855
TI  - Facial emotion recognition in violent men.
AB  - The goal of this study was to explore the ability of violent men to recognise
      facial affect. In contrast to traditional approaches to this research question,
      we took the effects of the models' sex and different types of violent behaviour
      into consideration. Data obtained from 71 violent men revealed that they
      recognised facial expressions of fear (p = .019) and disgust (p = .013) more
      accurately when displayed by female than male models. The opposite was found for
      angry faces (p = .006), while the models' sex did not affect the recognition of
      sad, happy and surprised facial expressions or neutral faces. Furthermore, sexual
      coercion perpetrators were more accurate than other violent men in the
      recognition of female facial disgust (p = .006). These results are discussed in
      the context of social learning theory, and the hypothesis that female facial
      expressions of disgust could be subtle cues to their sexual infidelity that
      motivate sexual coercion in some men.

PMID- 30105856
TI  - Isotopic evidence of biotrophy and unusual nitrogen nutrition in soil-dwelling
      Hygrophoraceae.
AB  - Several lines of evidence suggest that the agaricoid, non-ectomycorrhizal members
      of the family Hygrophoraceae (waxcaps) are biotrophic with unusual nitrogen
      nutrition. However, methods for the axenic culture and lab-based study of these
      organisms remain to be developed, so our current knowledge is limited to field
      based investigations. Addition of nitrogen, lime or organophosphate pesticide at
      an experimental field site (Sourhope) suppressed fruiting of waxcap basidiocarps.
      Furthermore, stable isotope natural abundance in basidiocarps were unusually high
      in 15 N and low in 13 C, the latter consistent with mycorrhizal nutritional
      status. Similar patterns were found in waxcap basidiocarps from diverse habitats
      across four continents. Additional data from 14 C analysis of basidiocarps and 13
      C pulse label experiments suggest that these fungi are not saprotrophs but rather
      biotrophic endophytes and possibly mycorrhizal. The consistently high but
      variable delta15 N values (10-200/00) of basidiocarps further indicate that N
      acquisition or processing differ from other fungi; we suggest that N may be
      derived from acquisition of N via soil fauna high in the food chain.

PMID- 30105857
TI  - From somatic mutation to early detection: insights from molecular
      characterization of pancreatic cancer precursor lesions.
AB  - Pancreatic cancer arises from noninvasive precursor lesions, including pancreatic
      intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasm
      (IPMN), and mucinous cystic neoplasm (MCN), which are curable if detected early
      enough. Recently, these types of precursor lesions have been extensively
      characterized at the molecular level, defining the timing of critical genetic
      alterations in tumorigenesis pathways. The results of these studies deepen our
      understanding of tumorigenesis in the pancreas, providing novel insights into
      tumor initiation and progression. Perhaps more importantly, they also provide a
      rational foundation for early detection approaches that could allow clinical
      intervention prior to malignant transformation. In this review, we summarize the
      results of comprehensive molecular characterization of PanINs, IPMNs, and MCNs
      and discuss the implications for cancer biology as well as early detection.
      Copyright (c) 2018 Pathological Society of Great Britain and Ireland. Published
      by John Wiley & Sons, Ltd.

PMID- 30105858
TI  - Lymphedema in patients with hidradenitis suppurativa: a systematic review of
      published literature.
AB  - BACKGROUND: Lymphedema is a debilitating complication of hidradenitis suppurativa
      (HS) that can be therapeutically challenging. Systematic evaluation of the
      clinical presentation and management of this condition has yet to be performed.
      METHODS: OVID MEDLINE and EMBASE databases were searched along with a review of
      the references of searched articles for all English reports discussing lymphedema
      secondary to HS. RESULTS: Two case series and 15 case reports met inclusion
      criteria, representing 27 patients. On average, these patients had a history of
      HS for 18 years (range 4-30 years). Lymphedema was found in the following areas
      in order of frequency: scrotum (16 patients, 59%), penis (12 patients, 44%),
      labia majora (4 patients, 15%), perineum (3 patients, 11%), groin (3 patients,
      11%), buttocks (2 patients, 7%), and abdomen (1 patient, 4%). In six patients
      (22%), lymphedema occurred in two or more of the aforementioned locations.
      Lymphedema most commonly presented not only as swelling with induration but also
      as verrucous papules or nodules. The majority of cases (14 patients, 52%) were
      treated with radical surgical excision combined with medical therapy and obtained
      favorable outcomes. Surgical defect was most frequently covered with split
      thickness skin grafts 7 patients, 54%) followed by skin flaps (3 patients, 11%)
      and healing by secondary intention (3 patients, 11%). CONCLUSIONS: Lymphedema
      appears to be a relatively rare complication of chronic HS that most commonly
      affects the anogenital region. Based on the evidence available, dermatologists
      should pursue a collaborative approach with surgery in the management of this
      condition at early stages.

PMID- 30105859
TI  - Sirtuin6 inhibits c-triggered inflammation through TLR4 abrogation regulated by
      ROS and TRPV1/CGRP.
AB  - Propionibacterium acnes induces inflammatory and plays a vital role in the
      formation of comedones through activation of inflammatory cells, keratinocytes,
      and sebocytes. Sirtuin6 (SIRT6), along with ADP-ribosyltransferase and
      deacetylase, has been proposed to mediate various biological functions, including
      inflammation. Nevertheless, no strong experimental evidence has been provided to
      support the effect of SIRT6 in treatment of inflammatory situation. Therefore,
      this study addressed the inhibitory effect of SIRT6 against P. acnes-triggered
      inflammation in human keratinocytes and monocyte cell lines. In our study,
      proinflammation capacity of P. acnes was confirmed by increased levels of various
      inflammatory modulators, such as interleukin (IL)-1beta, IL-6, IL-12, monocyte
      chemoattractant protein-1, interferon-gamma, and tumor necrosis facto-alpha, both
      in vivo and in vitro. P. acnes stimulation also decreased SIRT6 expression,
      whereas, SIRT6 overexpression successfully suppressed the production of these
      cytokines in P. acnes-infected cells, and therefore controlled inflammation.
      Furthermore, we found that challenge of P. acnes stimulated the expression of
      toll-like receptor 4 (TLR4) in both cell lines. Nevertheless, SIRT6
      overexpression attenuated the expression of TLR4 and consequently inhibited the
      P. acnes-triggered phosphorylation of nuclear transcription factor-kappa B (NF
      kappaB) subunit, p65. Moreover, deactivation of TLR4 signaling pathway by SIRT6
      overexpression resulted in significant downregulation of the transient receptor
      potential vanilloid (TRPV) pathway, cAMP response element-binding protein
      (CREB)/calcitonin gene-related peptide (CGRP) signaling, and NF-kappaB-regulated
      production of reactive oxygen species. These results indicate that SIRT6 serves
      as a potential therapeutic target to alleviate acne inflammation.

PMID- 30105860
TI  - A comparative study of magnetic resonance imaging on the gray matter and resting
      state function in prodromal and first-episode schizophrenia.
AB  - It is very difficult to predict the future development possibility of
      schizophrenia through the clinical symptoms of the high-risk cases. Therefore,
      how to determine the possibility of developing into schizophrenia individuals
      before the onset of the diseases are particularly important. The study
      investigated cerebral gray matter volume differences and resting-state functional
      connections among patients with psychosis risk syndrome (PRS), patients with
      first-episode schizophrenic (FES), and healthy controls (HC), aiming to provide
      scientific clinical evidence for schizophrenia early identification and
      intervention. A total of 19 PRS patients, 18 FES patients, and 29 HC were
      recruited. Gray matter volume and amplitude of low-frequency fluctuation (fALFF)
      during resting-state functional studies were measured. Comparison of gray matter
      volumes showed that PRS and FES groups had common reduced gray matter volume in
      the right caudate. PRS and FES patients showed altered connectivity mainly in the
      semantic processing-related brain areas. fALFF analysis found that PRF and FES
      patients had significant differences in fALFF values of the brain region mainly
      located in the subcortical network, visual recognition network, and auditory
      network. In addition, PRF individuals had a higher fALFF value and a lower fALFF
      value in the anterior wedge of the cerebral network than the HC group. Gray
      matter volume loss between related brain areas might appear prior to illness
      onset. Similar fALFF values occurred in PRS and FES groups indicated that
      multiple brain regions of neuronal activity abnormalities and unconventional
      neural network mechanism have been existed in PRS patients.

PMID- 30105862
TI  - Peripheral pain is enhanced by insulin-like growth factor 1 and its receptors in
      a mouse model of type 2 diabetes mellitus.
AB  - BACKGROUND: Insulin-like growth factor 1 (IGF1) is a neurotrophic factor with
      many actions, including a possible hyperalgesic effect. This study investigated
      the effects of IGF1 on the overall behavior of diabetic mice and explored the
      possible mechanisms underlying IGF1-induced pain. METHODS: Mice were divided into
      five groups (db/m, db/db, vehicle-treated db/db, IGF1-treated db/db, and IGF1 +
      JB1-treated db/db mice). Behavioral studies were conducted using the hot plate
      and Von Frey tests after intraplantar injection of recombinant (r) IGF1 (50
      MUg/kg) and the IGF1 receptor (IGF1R) antagonist JB1 (6 MUg/mouse). Morphological
      changes in dorsal root ganglia (DRG) were evaluated using electron microscopy.
      Immunofluorescence was used to detect IGF1R expression and colocalisation with
      pain mediators in the DRG. Changes in the expression of IGF1R, extracellular
      signal-regulated kinase (ERK), and ras-associated factor-1 (c-raf) in the DRG
      were evaluated using western blotting. RESULTS: Intraplantar injection of rIGF1
      resulted in a hyperalgesic effect after 2 hours. This IGF1-induced
      hypersensitivity was attenuated by prior intraplantar injection of the IGF1R
      antagonist. There was no significant change in neuronal structure in the db/m
      group, whereas neuronal structure was impaired in the other four groups.
      Moreover, IGF1R was colocalised with pain mediators in the DRG of mice.
      Intraplantar injection of rIGF1 resulted in increased IGF1R, phosphorylated (p-)
      ERK, and c-raf expression in the DRG; prior intraplantar injection of the IGF1R
      antagonist attenuated rIGF1-induced increases in p-ERK and c-raf. CONCLUSIONS:
      The results indicate that IGF1-induced acute hyperalgesia may be associated with
      the IGF1R/c-raf/ERK pathway. The IGF1-induced hypersensitivity was attenuated by
      an IGF1R antagonist.

PMID- 30105861
TI  - SOCIOEMOTIONAL AND BEHAVIORAL PROBLEMS IN TODDLERS WITH LANGUAGE DELAY.
AB  - Toddlers with language delay are at risk for persistent developmental and
      behavioral difficulties; however, the association between socioemotional/behavior
      problems and language in young children is not well understood. This study
      explored socioemotional/behavior problems in a unique sample of toddlers with
      language delays using a measure developed explicitly for this age group. Toddlers
      identified by 18 months with receptive and expressive language delay (LD; n = 30)
      or typical development (TD; n = 61) were evaluated at 18 and 24 months of age
      using the Infant-Toddler Social and Emotional Assessment (ITSEA) and the Mullen
      Scales of Early Learning. Compared to toddlers who had TD, toddlers with LD had
      significantly more concerning scores at 18 and 24 months on all ITSEA domains.
      The rate of "clinical concern" on most domains was not high in either group,
      except that >60% of LD toddlers were in the clinical concern range on the
      Competence domain. Socioemotional/behavioral problems were dimensionally related
      to receptive and expressive language, with greater language delay associated with
      more concerning ITSEA scores. Socioemotional and behavioral problems are related
      to receptive and expressive language abilities in 18- and 24-month-olds,
      indicating the need for screening of both types of concerns in toddlers
      identified with potential language delays.

PMID- 30105863
TI  - Effect of miconazole nitrate on immunological response and its preventive
      efficacy in Labeo rohita fingerlings against oomycetes Saprolegnia parasitica.
AB  - This study evaluated the effect of sublethal doses of antifungal drug miconazole
      nitrate (MCZ) on immunological responses and its role as a prophylactic drug
      against S. parasitica in Labeo rohita fingerlings. Fish were fed with sublethal
      doses of MCZ, that is, T1-6.30 mgMCZ kgBW-1 , T2-12.61 mgMCZ kgBW-1 and T3-25.22
      mgMCZ kgBW-1 , and sampling was done at different time intervals for 240 hr.
      Immunological parameters viz. lysozyme activity, oxygen radical production and
      plasma antiprotease activity showed significant enhancement (p < 0.05) in fish
      fed with T2 and T3 doses. Expression of immune-relevant genes such as TLR-22 and
      beta2-M showed significantly higher expression at 6 hr and 24 hr of sampling in
      both liver and head kidney. However, these genes showed a downregulation after
      120 hr of sampling in both the tissues. Preventive efficacy study showed that
      single dose of MCZ provides protection against oomycetes up to the fourth day of
      infection. Significantly higher mortality was observed in control diet-fed fish
      as compared to fish fed with MCZ medicated diet. Thus, it can be concluded that
      the MCZ can act as a potent antifungal agent for preventing oomycetes infection
      as well as to enhance the immune response.

PMID- 30105864
TI  - Cell cycle acceleration and changes in essential nuclear functions induced by
      simulated microgravity in a synchronized Arabidopsis cell culture.
AB  - Zero gravity is an environmental challenge unknown to organisms throughout
      evolution on Earth. Nevertheless, plants are sensitive to altered gravity, as
      exemplified by changes in meristematic cell proliferation and growth. We found
      that synchronized Arabidopsis-cultured cells exposed to simulated microgravity
      showed a shortened cell cycle, caused by a shorter G2/M phase and a slightly
      longer G1 phase. The analysis of selected marker genes and proteins by
      quantitative polymerase chain reaction and flow cytometry in synchronic G1 and G2
      subpopulations indicated changes in gene expression of core cell cycle regulators
      and chromatin-modifying factors, confirming that microgravity induced
      misregulation of G2/M and G1/S checkpoints and chromatin remodelling. Changes in
      chromatin-based regulation included higher DNA methylation and lower histone
      acetylation, increased chromatin condensation, and overall depletion of nuclear
      transcription. Estimation of ribosome biogenesis rate using nucleolar parameters
      and selected nucleolar genes and proteins indicated reduced nucleolar activity
      under simulated microgravity, especially at G2/M. These results expand our
      knowledge of how meristematic cells are affected by real and simulated
      microgravity. Counteracting this cellular stress is necessary for plant culture
      in space exploration.

PMID- 30105865
TI  - Gender dynamics in the donation field: human tissue donation for research,
      therapy and feeding.
AB  - This paper examines how gender dynamics shape human tissue donation for research
      and for human health. Drawing on research investigating the donation of different
      types of bodily tissues including blood, plasma, breastmilk, cord blood, foetal
      tissue and placentae we consider how and why women and men are viewed as
      different kinds of donors. We situate these donation practices within a broader
      understanding of gender difference to explain why any sociology of donation needs
      to take account of gender. In so doing we explore how tissue derived from the
      bodies of women acquires value in distinctive ways and for distinctive purposes
      and reasons. Within these gendered bioeconomies of donation, the supply and
      demand for tissue is structured by social understandings of maternity, parental
      responsibility, and risk, which in turn affect the experiences of donors.

PMID- 30105869
TI  - Functional morphology and paleoecology of Pilosa (Xenarthra, Mammalia) based on a
      two-dimensional geometric Morphometrics study of the Humerus.
AB  - The relationship between humerus shape and the modes of exploring substrate among
      extinct and extant Pilosa (especially anteaters and ground sloths) were
      investigated here. We used geometric morphometrics and discriminant analyses to
      relate morphological patterns and their possible ecological categories. Our
      results suggest that plesiomorphic taxa such as Nothrotheriidae, most
      Megalonychidae and basal Megatheriidae tend to have more slender humerus,
      associated to generalist habitus (climbing, swimming and digging activities), and
      while Mylodontidae developed specialized digging habitus. Additionally, we
      inferred ground sloths which inhabited the Brazilian territory during the
      Quaternary likely occupied at least four different niches. Mammals display
      morphofunctional adaptations on the limbs which are reflected on their modes of
      substrate exploration. Herein, we analyzed the humerus morphology of ground
      sloths and anteaters. Our results suggest that most of the Pleistocene Mylodonts
      were fossorial taxa, while most of the Santacrucian sloths plus extant anteaters
      were semiarboreal or semiaquatic taxa. The Pleistocene Megatheriidae should be
      ambulatory.

PMID- 30105866
TI  - Long noncoding RNA HOXB13-AS1 regulates HOXB13 gene methylation by interacting
      with EZH2 in glioma.
AB  - Dysregulation of long noncoding RNAs (lncRNAs) has been implicated in human
      diseases, in particular, cancers. In this study, we determined the expression of
      an lncRNA, HOXB13-AS1, involving in glioma. We showed that HOXB13-AS1 was
      significantly upregulated in glioma tissues and cells and was negatively
      correlated with its surrounding gene HOXB13 levels. Functional experiments in
      vitro and in vivo revealed that high level of HOXB13-AS1 increased cell
      proliferation and tumor growth by promoting cell cycle progression. Conversely,
      knockdown of HOXB13-AS1 resulted in decreased cell proliferation and tumor
      growth. Mechanistically, we showed that HOXB13-AS1 overexpression increased
      DNMT3B-mediated methylation of adjacent gene HOXB13 promoter by binding with the
      enhancer of zeste homolog 2 (EZH2) using bisulfite sequencing PCR (BSP),
      epigenetically suppressing HOXB13 expression. Additionally, the interaction
      between HOXB13-AS1 and HOXB13 was validated by RNA immunoprecipitation (RIP) and
      chromatin immunoprecipitation (ChIP) assays using antibody against to EZH2. Taken
      together, our study indicated that HOXB13-AS1 could regulate HOXB13 gene
      expression by methylation HOXB13 promoter and acts as an epigenetic oncogenic in
      glioma.

PMID- 30105868
TI  - A Tethered Tolane: Twisting the Excited State.
AB  - The synthesis of a doubly bridged tolane is reported. The target is obtained in a
      five-step synthesis, starting from commercially available 2-amino-meta-xylene by
      a combination of a Sandmeyer reaction, radical bromination, and Stille-type
      coupling, followed by double ring closing. The doubly tethered tolane is
      crystalline; the two phenyl rings are highly twisted with respect to each other
      both in solution and in the solid state. Optical spectroscopy and quantum
      chemical calculations show that the doubly bridged tolane is twisted not only in
      the ground state, but also in the excited state, leading to emission from the
      twisted state in solution and in the solid state. Strong phosphorescence is
      observed at cryogenic temperatures.

PMID- 30105870
TI  - Circulating cell-free DNA and ineffective erythropoiesis in nontransfusion
      dependent beta-thalassemia.

PMID- 30105867
TI  - Hippocampal amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid GluA1 (AMPA GluA1)
      receptor subunit involves in learning and memory improvement following treatment
      with Centella asiatica extract in adolescent rats.
AB  - INTRODUCTION: Centella asiatica is an herbal plant that contains phytochemicals
      that are widely believed to have positive effects on cognitive function. The
      adolescent stage is a critical development period for the maturation of brain
      processes that encompass changes in physical and psychological systems. However,
      the effect of C. asiatica has not been extensively studied in adolescents. The
      aim of this study was therefore to investigate the effects of a C. asiatica
      extract on the enhancement of learning and memory in adolescent rats. METHODS:
      The locomotor activity, learning, and memory were assessed by using open field
      test and water T-maze test. This study also examined changes in neuronal cell
      morphology using cresyl violet and apoptosis staining. We also performed
      immunohistochemical study to analyse the expression of the glutamate AMPA
      receptor (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) GluA1 subunit
      and the GABA receptor (gamma-Aminobutyric Acid) subtype GABAA alpha1 subunit in
      the hippocampus of the same animals. RESULTS: We found no significant changes in
      locomotor activity (p > 0.05). The water T-maze data showed that 30 mg/kg dose
      significantly (p < 0.05) improved learning, memory, and the memory consolidation
      phase but had no effect on reversal learning (p > 0.05). Histological data
      revealed no neuronal morphological changes. Immunohistochemical analysis revealed
      increased expression of the AMPA GluA1 receptor subunit but there was no effect
      on GABAA receptor alpha1 subunit expression in the CA1 and CA2 subregions of the
      hippocampus. CONCLUSIONS: The C. asiatica extract therefore improved hippocampus
      dependent spatial learning and memory in a dose-dependent manner in rats through
      the GluA1-containing AMPA receptor in the CA1 and CA2 sub regions of the
      hippocampus.

PMID- 30105871
TI  - Comparison of PD-L1 immunohistochemistry assays and response to PD-1/L1
      inhibitors in advanced non-small-cell lung cancer in clinical practice.
AB  - AIMS: Several studies have demonstrated analytical comparability between
      different PD-L1 assays, but their clinical validity in non-small-cell lung cancer
      in terms of response to treatment outside clinical trials has not been
      established. The aim of our study is to assess the analytical performance of
      laboratory-developed tests for Ventana SP263 and Agilent/Dako 22C3, and to
      investigate the association between PD-L1 assays and response to PD-1/L1
      inhibitors. METHODS AND RESULTS: PD-L1 SP263 and 22C3 assays were performed on
      302 consecutive non-small-cell lung carcinoma samples Both assays were optimised
      for use on the automated Ventana BenchMark Ultra platform. Scoring algorithms for
      staining of the tumour cells using the established cut-offs were applied to all
      samples. Best overall response (BOR) for 44 patients treated with either
      nivolumab, pembrolizumab or atezolizumab were assessed using recist version 1.1
      and correlated with PD-L1 assay results. Assays showed good agreement, with a
      concordance correlation coefficient of 0.86 [95% confidence interval (CI) = 0.82
      0.90)]. Comparing the assays using cut-offs of 1%, 5%, 10%, 1-49% and >=50%
      showed an association between the two assays (P < 0.0001). The SP263 10% cut-off
      (P = 0.032) was associated with BOR, whereas the 1% (P = 0.087) and 5% (P =
      0.051) cut-offs were not. In contrast 22C3, cut-offs of 1% (P = 0.019), 5% (P =
      0.025) and 10% (P = 0.014) were all associated with BOR. CONCLUSIONS: The SP263
      and 22C3 LDTs demonstrated good analytical concordance, and correlation with
      response to PD-1/L1 inhibitors.

PMID- 30105872
TI  - Cryopreservation media differentially affect sperm motility, morphology and DNA
      integrity.
AB  - INTRODUCTION: Human sperm freezing is very widely used for male fertility
      preservation. This procedure consists in adding cryoprotectants to the
      spermatozoa followed by cooling and storing the spermatozoa at a subzero
      temperature. Many standardized cryopreservation media are available on the
      market. However, these media differ in their chemical composition and there are
      no sufficient data to optimize their classification. Therefore, the aim of this
      study was to compare five commercially available sperm cryopreservation media,
      which have not been compared together, in terms of motility, morphology and DNA
      integrity. MATERIALS AND METHODS: One-hundred semen samples were obtained from 10
      fertile participants and 90 infertile men. Each sample was evaluated before
      freezing for motility, morphology and DNA fragmentation index (DFI). Then, it was
      equally divided into five aliquots. Each aliquot was cryopreserved using one of
      the five media (A, B, C, D, and E). The same parameters were re-evaluated after
      the addition of the cryopreservation media in the fertile group, and after sperm
      thawing in fertile and infertile groups. RESULTS: The results showed that the
      five selected cryopreservation media had negative effects on sperm motility and
      morphology per se. In the infertile group, the cryosurvival factor was
      significantly lower in cryomedium A when compared to the four other media (p <
      0.001). In addition, a significantly higher percentage of sperm with coiled tail
      was detected in cryomedium E compared to cryomedium A (p < 0.05) and to
      cryomedium B (p < 0.001) after thawing, in the infertile group. Furthermore, the
      sperm DFI was significantly higher in cryomedia A (p < 0.001), B (p < 0.001), C
      (p < 0.01), D (p < 0.01) and E (p < 0.05) compared to that of the fresh semen
      derived from infertile participants. CONCLUSION: This study indicates that the
      recovery rate of competent spermatozoa, after cryopreservation, is still critical
      in infertile men. Therefore, frozen semen sample should be used only when
      necessary.

PMID- 30105873
TI  - Neurochemical characterization of intramural nerve fibres in the porcine
      oesophagus.
AB  - The gastrointestinal (GI) tract is innervated by nerve processes derived from the
      intramural enteric neurons and neurons localized outside the digestive tract.
      This study analysed the neurochemical characterization of nerves in the wall of
      the porcine oesophagus using single immunofluorescence technique.
      Immunoreactivity to vesicular acetylcholine transporter (VAChT), neuropeptide Y
      (NPY), vasoactive intestinal polypeptide (VIP), somatostatin (SOM), galanin
      (GAL), neuronal isoform of nitric oxide synthase (nNOS), substance P (SP),
      leucine enkephalin (LENK), calcitonin gene-related peptide (CGRP) or dopamine
      beta-hydroxylase (DBH) was investigated in intramuscular and intramucosal nerves
      of the cervical, thoracic and abdominal oesophagus. The results indicate that all
      of the substances studied were present in the oesophageal nerves. The density of
      particular populations of fibres depended on the segment of the oesophagus. The
      most numerous were fibres immunoreactive to VIP in the longitudinal and circular
      muscle layers of the abdominal oesophagus: The number of these fibres amounted to
      16.4 +/- 0.8 and 18.1 +/- 3.1, respectively. In turn, the least numerous were
      CGRP-positive fibres, which were present only in the circular muscle layer of the
      cervical oesophagus and mucosal layer of the abdominal oesophagus in the number
      of 0.3 +/- 0. The obtained results show that nerves in the porcine oesophageal
      wall are very diverse in their neurochemical coding, and differences between
      particular parts of the oesophagus suggest that organization of the innervation
      clearly depends on the fragment of this organ.

PMID- 30105874
TI  - Change of miRNA expression profiles in patients with knee osteoarthritis before
      and after celecoxib treatment.
AB  - BACKGROUND: This study aimed to investigate the change of circulating miRNA
      expression profiles in knee osteoarthritis (OA) patients before and after
      celecoxib treatment. METHODS: Two hundred and eighteen knee OA patients underwent
      celecoxib treatment for 6 weeks were enrolled. Plasma samples were obtained at
      baseline (W0) and at W6, and treatment efficacy were assessed by WOMAC index. In
      the exploration stage, miRNA expression profiles in plasma before and after
      treatment from 6 patients were detected by microarray. Subsequently, in the
      validation stage, 10 top differentially expressed miRNAs (DEMs) after and before
      treatment in microarray were further validated in all 218 patients by qPCR.
      RESULTS: In the exploration stage, patients after treatment could be
      distinguished from them before treatment by miRNAs expression profiles by PCA
      plot and heatmap analysis, and 45 up-regulated and 48 down-regulated miRNAs were
      identified by volcano plot. In the validation stage, miR-126-5p and miR-320a
      levels increased at W6 compared to W0, while miR-155-5p and miR-146a-5p levels
      decreased. WOMAC pain/stiffness/physical function scores were all decreased at W6
      compared to W0, and 71% of patients achieved clinical response. The increase of
      miR-126-5p expression (W6-W0) in clinical responders was much larger compared to
      nonclinical responders. And miRNA-320a level declined in nonclinical responders
      while increased in clinical responders. Conversely, miRNA-146a-5p level increased
      in nonclinical responders while decreased in clinical responders. CONCLUSION:
      Circulating miRNA expression profiles act as important roles in knee OA patients
      underwent celecoxib treatment, and miR-126-5p, miR-320a as well as miR-146a-5p
      might correlate with treatment response to celecoxib.

PMID- 30105875
TI  - Brief Emotion Focused Family Therapy: An Intervention for Parents of Children and
      Adolescents with Mental Health Issues.
AB  - This study evaluated the 2-day intensive modality of Emotion Focused Family
      Therapy (EFFT). The intervention attempts to prepare parents to take a primary
      role in their child's recovery from a range of mental health issues. One hundred
      and twenty-four parents completed the intervention and provided data a week prior
      to intervention, post-intervention and at 4-month follow-up. Results include
      significantly reduced parent blocks and increased parental self-efficacy in
      relation to involvement in their child's recovery, as well as significant
      improvement in child symptomatology. The findings confirm positive results from
      an earlier pilot study involving eating disorders and demonstrate the potential
      for EFFT as an intervention for a range of clinical problems in children and
      youth.

PMID- 30105876
TI  - Long noncoding RNA DQ786243 interacts with miR-506 and promotes progression of
      ovarian cancer through targeting cAMP responsive element binding protein 1.
AB  - Long noncoding RNAs (lncRNAs) have been reported to be abnormally expressed in
      several cancers and associated with the proliferation of cancer cells. The
      objective of this study was to investigate the role and the underlying mechanisms
      of DQ786243 in ovarian cancer. In the current study, DQ786243 was specifically
      upregulated in ovarian cancer tissues and cell lines. Knockdown of DQ786243
      inhibited the ability of cell migration, invasion, proliferation, colony
      formation and wound healing, whereas promoted cell apoptosis and induced G0/G1
      cell cycle arresting. By using online tools and mechanistic analysis, we
      demonstrated that DQ786243 could directly bind to microRNA-506 (miR-506) and
      downregulate its expression. Moreover, DQ786243 reversed the inhibitory effect of
      miR-506 on the growth of ovarian cancer cells, which might be involved in the
      derepression of cAMP responsive element binding protein 1 (CREB1) expression.
      Further investigation into the mechanisms showed that knockdown of DQ786243
      inhibited the epithelial to mesenchymal transition (EMT) process in ovarian
      cancer cells. Finally, xenograft experiments further confirmed that knockdown of
      DQ786243 notably suppressed the proliferation and EMT process in vivo. Taken
      together, our study showed for the first time that DQ786243 interacted with miR
      506 and promoted progression of ovarian cancer via targeting CREB1 in ovarian
      cancer. The results might help to probe the feasibility of lncRNA-directed
      therapy for this deadly disease.

PMID- 30105877
TI  - Prenatal physiologic findings and postnatal advanced imaging in the management of
      absent pulmonary valve syndrome with intact ventricular septum.
AB  - Absent pulmonary valve syndrome is a congenital heart defect usually associated
      with tetralogy of Fallot. Rarely, absent pulmonary valve syndrome can occur
      independently of tetralogy of Fallot and presents with an intact ventricular
      septum and a patent ductus arteriosus. This case report describes the prenatal
      diagnosis of absent pulmonary valve syndrome with intact ventricular septum via
      echocardiogram and the postnatal management of the resulting physiologic effects
      secondary to this rare congenital heart disease.

PMID- 30105878
TI  - Outcomes in thread lift for face and neck: A study performed with Silhouette Soft
      and Promo Happy Lift double needle, innovative and classic techniques.
AB  - INTRODUCTION: Increased demand for rejuvenation of the aging face has led to the
      evolution of various plastic surgery techniques. This study was conducted to
      evaluate the surgical efficacy and outcomes of the absorbable suture suspension
      system related to eyebrow, midface, mandibular, and neck lifting. MATERIALS AND
      METHODS: In this prospective review chart clinical study, a total of 193 patients
      were included in the study from January 2016 to May 2017. All participants
      underwent thread lifting using the Proma Happy Lift double needle and Silhouette
      Soft threads. The patients were followed up for first week and first, third, and
      sixth month after lifting surgery. Outcomes were assessed by two surgeons and
      patients based on the GAIS score. RESULTS: A total of 193 patients (mean age:
      52.22 +/- 11.74 year, range: 25-89), 23 (11.9%) men and 170 (88.1%) women, were
      included in the study. The most common sites for the face lifting surgery were
      the jawline (46.1%), midface (33.7%), eyebrows (12.4%), and neck (7.8%). The
      level of satisfaction increased from 94% in the first week after surgery to 99%
      in the sixth month after surgery for patients, increased from 94% to 99% for
      surgeon 1, and increased from 83% to 98% for surgeon 2. CONCLUSION: The results
      showed that the level of satisfaction of patients and surgeons increased over
      time. These results demonstrated that facial rejuvenation thread lift with Proma
      Happy Lift double needle and Silhouette Soft threads is a being cosmetically more
      acceptance, safe, and effective procedure associated with minor complications.

PMID- 30105879
TI  - Is the 31 P chemical shift anisotropy of aluminophosphates a useful parameter for
      NMR crystallography?
AB  - The 31 P chemical shift anisotropy (CSA) offers a potential source of new
      information to help determine the structures of aluminophosphate (AlPO) framework
      materials. We investigate how to measure the CSAs, which are small (span of ~20
      30 ppm) for AlPOs, demonstrating the need for CSA-amplification experiments
      (often in conjunction with 27 Al and/or 1 H decoupling) at high magnetic field
      (20.0 T) to obtain accurate values. We show that the most shielded component of
      the chemical shift tensor, delta33 , is related to the length of the shortest P?O
      bond, whereas the more deshielded components, delta11 and delta22 can be related
      more readily to the mean P?O bond lengths and P?O?Al angles. Using the case of Mg
      doped STA-2 as an example, the CSA is shown to be much larger for P(OAl)4-n
      (OMg)n environments, primarily owing to a much shorter P?O(Mg) bond affecting
      delta33 , however, because the mean P?O bond lengths and P?O?T (T = Al, Mg) bond
      angles do not change significantly between P(OAl)4 and P(OAl)4-n (OMg)n sites,
      the isotropic chemical shifts for these species are similar, leading to
      overlapped spectral lines. When the CSA information is included, spectral
      assignment becomes unambiguous, therefore, although the specialist conditions
      required might preclude the routine measurement of 31 P CSAs in AlPOs, in some
      cases (particularly doped materials), the experiments can still provide valuable
      additional information for spectral assignment.

PMID- 30105880
TI  - Mobile technology use and skills among individuals with fragile X syndrome:
      implications for healthcare decision making.
AB  - BACKGROUND: Little is known about how individuals with fragile X syndrome (FXS)
      and their families use technology in daily life and what skills individuals with
      FXS can perform when using mobile technologies. METHODS: Using a mixed-methods
      design, including an online survey of parents (n = 198) and a skills assessment
      of individuals with FXS (n = 6), we examined the experiences and abilities of
      individuals with FXS for engaging with mobile technology. RESULTS: Parents
      reported that individuals with FXS often used technology in their daily lives,
      with variations based on age of child, sex, autism status, depression, and
      overall ability. Parents frequently sought and shared FXS-related information
      online. Assessment data revealed that individuals with FXS demonstrated
      proficiency in interacting with technology. CONCLUSIONS: Mobile technology is a
      tool that can be used in FXS to build skills and increase independence rather
      than simply for recreational purposes. Implications for using mobile technology
      to enhance healthcare decision making are discussed.

PMID- 30105881
TI  - Identification of PfENR inhibitors: A hybrid structure-based approach in
      conjunction with molecular dynamics simulations.
AB  - In the current study, we have constructed receptor-based pharmacophore models by
      exploiting the Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR)
      structural proteome. The derived models were subjected to a series of validation
      procedures to list the representative hypotheses that can be used for the
      screening of the Drug-like Diverse Database. A set of 739 molecules was retrieved
      and analyzed for the adsorption, distribution, metabolism, excretion and toxicity
      (ADMET) and drug-likeness attributes. The filtered drug-like molecules (64) were
      then subjected to molecular docking and HYDE assessment studies. The hybrid
      structure-based approach yielded 4 molecules, UKR1308259, ENA1096786, UKR403454,
      and ASI51224, as PfENR inhibitors. The stability of these inhibitors was assessed
      using molecular mechanics-generalized born surface area approach-based free
      binding energy calculations and molecular dynamics simulations. Molecular
      mechanics-generalized born surface area calculations and molecular dynamics
      simulations showed that UKR1308259, ENA1096786, and ASI51224 were more potent
      PfENR inhibitors. The rationale behind the current work was to identify orally
      available inhibitor molecules with diverse scaffolds that could serve as initial
      leads for the drug design against PfENR.

PMID- 30105882
TI  - Influence of food texture on energy metabolism and adiposity in male rats.
AB  - NEW FINDINGS: What is the central question of this manuscript? What is the effect
      of food texture on fat accumulation, lipogenesis and proinflammatory factors in
      the adipose tissue and on energy balance in male rats? What is the main finding
      and its importance? Calorie intake and fat accumulation in rats fed soft pellets
      ad libitum increased, but their body weight did not. The data suggest that, even
      when BMI is normal, frequent consumption of soft food may contribute to the
      development of lifestyle-related diseases. ABSTRACT: Dietary factors such as food
      texture are known to affect feeding behaviour and energy metabolism. We recently
      found that rats fed soft pellets (SPs) on a 3 h restricted feeding schedule
      showed glucose intolerance, insulin resistance with disruption of insulin
      signalling, and hyperplasia of pancreatic beta-cells, even though there were no
      differences in energy intake and body weight between rats fed control pellets
      (CPs) and rats fed SPs. We investigated the effect of food texture on fat
      accumulation, lipogenesis and proinflammatory factors in the mesenteric fat, as
      well as on energy balance in male rats fed CPs or SPs. We used 7-week-old Wistar
      rats that were randomly divided into two groups, ad libitum fed either CPs or SPs
      for 27 weeks. Body weight and calorie intake were monitored once a week
      throughout the experiment. The calorie intake, lipogenesis and fat accumulation
      of the rats fed SPs increased, whereas their body weight did not. Additionally,
      SP rats used their fat mainly as a source of energy and increased their energy
      expenditure. Our data suggest that the habit of frequently eating soft food
      causes visceral fat accumulation without an increase in body weight. Further
      investigations using soft-textured foods could lead to the development of
      appropriate interventions for non-overweight patients with lifestyle-related
      diseases.

PMID- 30105883
TI  - Prevalence of early loss of primary molar and its impact in schoolchildren's
      quality of life.
AB  - BACKGROUND: Evidence regarding the impact of premature loss of primary molars on
      oral health-related quality of life (OHRQoL) is lacking. AIM: To evaluate the
      prevalence of premature loss of primary molars in schoolchildren and its impact
      on OHRQoL. DESIGN: We randomly selected 667 children aged 8-9 years enrolled in
      public and private schools from Aracaju (Brazil). The presence of untreated
      dental caries and early loss of primary molars were recorded, and its impacts on
      OHRQoL evaluated using Child Perceptions Questionnaire (CPQ8-10 ). Influence of
      some variables on tooth loss and OHRQoL was assessed by multilevel Poisson's
      regression analysis (P < 0.05). RESULTS: The prevalence for early tooth loss was
      65.4% (95% confidence interval 51.1%-77.3%). Children with untreated dental
      caries and attending public schools presented higher prevalence of early tooth
      loss. Moreover, early loss of primary molars provoked negative impact on OHRQoL
      considering total score of CPQ8-10 and domains "oral symptoms," "functional
      limitations" and "emotional well-being." Children presenting early teeth loss
      presented significantly higher scores of CPQ8-10 , as well as females and
      children with dental caries in other teeth. CONCLUSIONS: The prevalence of early
      loss of primary molars is high, and it impacts the OHRQoL of children aged 8-9
      years.

PMID- 30105884
TI  - The unravelled Enterococcus faecalis zoonotic superbugs: Emerging multiple
      resistant and virulent lineages isolated from poultry environment.
AB  - This study aimed to investigate the zoonotic potential by virtue of phylogenetic
      analysis, virulence and resistance gene profiles of Enterococcus faecalis
      originating from poultry environment. The ERIC, BOX and RAPD PCR analysis showed
      the clustering of E. faecalis strains (n = 74) into five groups (G1-G5) and
      fifteen sub-clusters (B1-B15), which share 50%-80% similarities with ATCC E.
      faecalis and clinical strains of human infection. E. faecalis strains harboured
      seven enterocins genes including ent1097 (85%), entB (84%), enterolysinA (51%),
      entSEK4 (51%), entL50 (31%), entA (25.7%) and ent1071 (14.9%). The highest
      prevalence of gelE-sprE (90%), lip-fl (90%) followed by cylL (62%), hyl (60%),
      katA (16%) and cylA (5.4%) was observed in poultry isolates. The fsr operon and
      gelE-sprE was co-associated in 66.2% strains. E. faecalis also harboured biofilm
      and endocarditis-associated genes, including efaAfs (97%), ebp-pilli (ebpABC and
      srtC 69.9%-80%), asa1 (71%), agg (55%), ace (54%) and esp-Tim (3%). Despite all
      found sensitive to vancomycin, 98.6% strains were multi-drug resistant to five to
      twelve tested antimicrobials. An increased-level of resistance (>=32 MUg/ml) was
      observed to ampicillin (8.1%), meropenem (21.6%), chloramphenicol (73.4%),
      erythromycin (90.5%), tetracycline (100%) and high-level resistance to kanamycin
      (79.7%) and gentamicin (52.7%). The multi-drug resistant E. faecalis (MDRe.f)
      were carried pbp4 (90%), tetL (90%), tetM (70%), ermB (81%), cat (52.7%), acc6
      aph2 (58.1%), aaph(3)-III (49.9%), gyrA (97%) and parC (98%) genes. Moreover,
      these MDRe.f were also harboured, hospital-associated marker IS16 (58%) and
      pheromone responsive genes, that is ccf (88%), cpd (74%), cob (62%) and eep
      (66%). Thus, regardless of the distinct phylogenetic background of E. faecalis of
      poultry origin, ATCC E. faecalis and clinical strains of human origin, we found
      major similarities in virulence, resistance gene profiles and mobile genetic
      elements (IS16 and pheromone responsive plasmids), supporting the
      zoonotic/reverse zoonotic risk associated with this organism.

PMID- 30105885
TI  - Association among chronotype, dietary behaviours, and caries experience in
      Brazilian adolescents: Is there a behavioural pattern?
AB  - BACKGROUND: Dental caries (DC) remains a public health issue. Chronotype, diet,
      and oral hygiene may influence its development. OBJECTIVE: To investigate the
      association of chronotype, diet, oral hygiene, and DC among 12-year-olds.
      METHODS: A cross-sectional study with 245 adolescents was conducted in public and
      private schools in southeast Brazil. Sociodemographics, dietary and oral hygiene
      habits were collected through a self-reported questionnaire. Chronotype was
      assessed using the Portuguese version of the Puberty and Phase Preference Scale
      (PPPS). Subjects were examined for DC (WHO criteria). Bivariate and multivariate
      analyses were performed (P < 0.05). RESULTS: DC was present in 42.0% of the
      sample. In the bivariate analysis, a higher DMFT was associated with living in
      rural areas (P = 0.006), parents'/caregivers' lower schooling (P = 0.008), and a
      not daily intake of vegetables (P = 0.033). Chronotype was not associated with
      DMFT scores. The Poisson regression model showed that adolescents who did not
      have breakfast regularly (PR = 1.55; 95% CI = 1.17-2.08; P = 0.003), lived in
      rural areas (PR = 2.20; 95% CI = 1.59-3.04; P < 0.001) and did not consume
      vegetables daily (PR = 1.55; 95% CI = 1.11-2.17; P = 0.009) were more likely to
      present a higher DMFT. CONCLUSIONS: DC is associated to living in rural areas and
      dietary habits, such as not having breakfast regularly and lack of daily intake
      of vegetables.

PMID- 30105888
TI  - Post-treatment apical periodontitis related to the technical quality of root
      fillings and restorations in Thai population.
AB  - The aim of this study was to investigate the post-treatment apical periodontitis
      in endodontically treated teeth related to the technical quality of root fillings
      and restorations in Thai population. Full-mouth periapical radiographs from Thai
      patients attending the Faculty of Dentistry, Mahidol University, Thailand were
      examined. The periapical status, quality of root fillings and coronal
      restorations, existence of intraradicular post and its relationship to the root
      fillings were evaluated. Among 1586 patients, 37.4% presented endodontically
      treated teeth. The total number of endodontically treated teeth was 1511, and 35%
      presented apical periodontitis. Combined data for root filling and coronal
      restoration qualities revealed significantly better outcome in teeth with
      adequate qualities of both parameters than the other combinations (P < 0.001).
      The prevalence of post-treatment apical periodontitis among Thai population was
      relatively high and significantly associated with substandard technical quality
      of root fillings and restorations.

PMID- 30105886
TI  - FgSec2A, a guanine nucleotide exchange factor of FgRab8, is important for
      polarized growth, pathogenicity and deoxynivalenol production in Fusarium
      graminearum.
AB  - Sec4/Rab8 is one of the well-studied members of the Rab GTPase family, previous
      studies have shown that Sec4/Rab8 crucially promotes the pathogenesis of
      phytopathogens, but the upstream regulators of Rab8 are still unknown. Here, we
      have identified two Sec2 homologues FgSec2A and FgSec2B in devastating fungal
      pathogen Fusarium graminearum and investigated their functions and interactions
      with FgRab8 by live-cell imaging, genetic and functional analyses. Yeast two
      hybrid assay shows that FgSec2A specifically interacts with FgRab8DN(N123I) and
      itself. Importantly, FgSec2A is required for growth, conidiation, DON production
      and virulence of F. graminearum. Live-cell imaging shows that FgSec2A and FgSec2B
      are both localized to the tip region of hyphae and conidia. Both N-terminal
      region and Sec2 domain of FgSec2A are essential for its function, but not for
      localization, whereas the C-terminal region is important for its polarized
      localization. Furthermore, constitutively active FgRab8CA(Q69L) partially rescues
      the defects of DeltaFgsec2A. Consistently, FgSec2A is required for the polarized
      localization of FgRab8. Finally, FgSec2A and FgSec2B show partial functions, but
      FgSec2A does not interact and co-localize with FgSec2B. Taken together, these
      results indicate that FgSec2A acts as a FgRab8 guanine nucleotide exchange factor
      and is necessary for polarized growth, DON production and pathogenicity in F.
      graminearum.

PMID- 30105887
TI  - The influence of treatment, age at onset, and metabolic control on height in
      children and adolescents with type 1 diabetes-A SWEET collaborative study.
AB  - OBJECTIVE: To describe the association between height, demographics, and
      treatment in youths with type 1 diabetes participating in an international
      network for pediatric diabetes centers (SWEET). METHODS: Data were collected from
      55 centers with documented patients' height. All subjects below 20 years of age,
      diabetes duration >1 year, and without celiac disease were included. World Health
      Organization growth charts were used to calculate height and body mass index z
      scores. Multiple hierarchic regression models adjusting for known confounders
      were applied. RESULTS: Data on 22 941 subjects (51.8% male) were analyzed with a
      median and interquartile range for age 14.8 years (11.2, 17.6), diabetes duration
      5.6 years (3.1, 8.9), and height z-score 0.34 (-0.37, 1.03). Children were taller
      in the youngest age groups: adjusted height z-scores of 0.31 (+/-0.06) and 0.39
      (+/-0.06), respectively; with shorter diabetes duration (<2 years: 0.36 [+/
      0.06]; 2-<5 years: 0.34 [+/-0.06]; >=5 years: 0.21 [+/-0.06]) and if they were
      pump users: 0.35 +/- 0.05 vs 0.25 +/- 0.05 (>three injections/day and 0.19 +/-
      0.06 [0-3 injections daily]), respectively. High hemoglobin A1c (HbA1c) and low
      to normal weight were associated with a lower height z-score. Trends were
      identical in all models except for gender. No gender differences were found
      except in the final height model where females exhibited higher z-score than
      males. CONCLUSION: For youths treated at centers offering modern diabetes
      management, major growth disturbances are virtually eliminated. For children with
      a young age at onset, high HbA1c, injections, and/or non-intensive diabetes,
      treatment still requires attention in order to attain normal growth.

PMID- 30105889
TI  - Level of accuracy of diagnoses recorded in discharge summaries: A cohort study in
      three respiratory wards.
AB  - RATIONALE: One of the key functions of the discharge summary is to convey
      accurate diagnostic description of patients. Inaccurate or missing diagnoses may
      result in a false clinical picture, inappropriate management, poor quality of
      care, and a higher risk of re-admission. While several studies have investigated
      the presence or absence of diagnoses within discharge summaries, there are very
      few published studies assessing the accuracy of these diagnoses. The aim of this
      study was to measure the accuracy of diagnoses recorded in sample summaries, and
      to determine if it was correlated with the type of diagnoses (eg, "respiratory"
      diagnoses), the number of diagnoses, or the length of patient stay. METHODS: A
      prospective cohort study was conducted in three respiratory wards in a large UK
      NHS Teaching Hospital. We determined the reference list of diagnoses (the closest
      to the true state of the patient based on consultant knowledge, patient records,
      and laboratory investigations) for comparison with the diagnoses recorded in a
      discharge summary. To enable objective comparison, all patient diagnoses were
      encoded using a standardized terminology (ICD-10). Inaccuracy of the primary
      diagnosis alone and all diagnoses in discharge summaries was measured and then
      correlated with type of diseases, number of diagnoses, and length of patient
      stay. RESULTS: A total of 107 of 110 consecutive discharge summaries were
      analysed. The mean inaccuracy rate per discharge summary was 55% [95% CI 52 to
      58%]. Primary diagnoses were wrong, inaccurate, missing, or mis-recorded as a
      secondary diagnosis in half the summaries. The inaccuracy rate was correlated
      with the type of disease but not with number of diagnoses nor length of patient
      stay. CONCLUSION: Our study showed that diagnoses were not accurately recorded in
      discharge summaries, highlighting the need to measure and improve discharge
      summary quality.

PMID- 30105890
TI  - Sparse multiple factor analysis to integrate genetic data, neuroimaging features,
      and attention-deficit/hyperactivity disorder domains.
AB  - OBJECTIVES: We proposed the application of a multivariate cross-sectional
      framework based on a combination of a variable selection method and a multiple
      factor analysis (MFA) in order to identify complex meaningful biological signals
      related to attention-deficit/hyperactivity disorder (ADHD) symptoms and
      hyperactivity/inattention domains. METHODS: The study included 135 children from
      the general population with genomic and neuroimaging data. ADHD symptoms were
      assessed using a questionnaire based on ADHD-DSM-IV criteria. In all analyses,
      the raw sum scores of the hyperactivity and inattention domains and total ADHD
      were used. The analytical framework comprised two steps. First, zero-inflated
      negative binomial linear model via penalized maximum likelihood (LASSO-ZINB) was
      performed. Second, the most predictive features obtained with LASSO-ZINB were
      used as input for the MFA. RESULTS: We observed significant relationships between
      ADHD symptoms and hyperactivity and inattention domains with white matter, gray
      matter regions, and cerebellum, as well as with loci within chromosome 1.
      CONCLUSIONS: Multivariate methods can be used to advance the neurobiological
      characterization of complex diseases, improving the statistical power with
      respect to univariate methods, allowing the identification of meaningful
      biological signals in Imaging Genetic studies.

PMID- 30105891
TI  - Investigation of a source model for a new electronic brachytherapy tandem by film
      measurement.
AB  - PURPOSE: To investigate the accuracy of a vendor-supplied source model for a new
      Xoft Axxent 0-degree titanium tandem by film measurement. METHODS: We measured
      the anisotropy factors at varying distances and angles from the tandem in water
      using radiochromic film (Gafchromic EBT3) and an Epson Perfection v750 desktop
      flatbed scanner (US Epson, Long Beach, CA). A 0-degree tandem was placed
      vertically in a water phantom. Four pieces of film, each at varying depths, were
      positioned orthogonal to the longitudinal axis of the tandem for azimuthal
      anisotropy measurements. Polar anisotropy measurements were taken with the film
      aligned parallel to the tandem. An absolute dose calibration for the film was
      verified with a PTW 34013 Soft X-Ray Chamber. The film measurements were analyzed
      using different color channels. The measured polar anisotropy for varying source
      positions was compared to the vendor's data. Azimuthal anisotropy was measured as
      a function of the radius and angle, and normalized to the mean value over all
      angles at the specified radius. RESULTS: The azimuthal anisotropy of the tandem
      and source was found to be consistent for different positions along the tandem's
      longitudinal axis and at varying distances from the tandem. Absolute dose using a
      calibrated parallel plate chamber showed agreement to within 2% of expected TPS
      values. The custom tandem, which has a thicker tip than the wall, was attenuating
      the 50 kV photons more than expected, at the angles where the photons had more
      wall material to traverse. This discrepancy was verified at different distances
      from the tandem and with different measurement techniques. As distance increased,
      anisotropy values had better agreement. CONCLUSIONS: We quantified the agreement
      between the measured and provided anisotropy factors for a new Xoft Axxent 0
      degree titanium tandem. Radiochromic film response at low kV energy was also
      investigated. Our results showed that vendor-supplied TG-43 values were
      appropriate for clinical use at majority of the angles. A rigorous quality
      assurance method for new electronic brachytherapy sources and applicators, along
      with complete knowledge of all dosimetric measuring tools, should be implemented
      for all parts of the verification and commissioning process.

PMID- 30105892
TI  - Ultra-Orthodox Jews and infertility diagnosis and treatment.
AB  - BACKGROUND: 'Be fruitful and multiply' is the first God's command in the Bible.
      Every aspect in life of the Orthodox Jewish population, including the strive for
      fertility, is tightly covered by a wide set of commands and rules ('Halacha')
      that span more than 3,000 years. This is a unique example of a population that
      continues to adhere to such time-honored rules. OBJECTIVE: To describe rules that
      encourage fertility on one hand, but may hinder fertility and influence
      infertility diagnosis and treatment on the other. MATERIALS AND METHODS: Halacha
      rules that may affect fecundity. RESULTS: Orthodox Jews obey a complex set of
      rules that influence fertility. DISCUSSION AND CONCLUSION: This study provides
      fertility practitioners with background information that may help them when
      delivering professional care to Ultra-Orthodox Jewish infertile couples.

PMID- 30105893
TI  - Sequence analysis of haemagglutinin gene of camelpox viruses shows deletion
      leading to frameshift: Circulation of diverse clusters among camelpox viruses.
AB  - Orthopoxviruses (OPVs) have broad host range infecting a variety of species along
      with gene-specific determinants. Several genes including haemagglutinin (HA) are
      used for differentiation of OPVs. Among poxviruses, OPVs are sole members
      encoding HA protein as part of extracellular enveloped virion membrane. Camelpox
      virus (CMLV) causes an important contagious disease affecting mainly young
      camels, endemic to Indian subcontinent, Africa and the Middle East. This study
      describes the sequence features and phylogenetic analysis of HA gene (homologue
      of VACV A56R) of Indian CMLV isolates. Comparative analysis of CMLV HA gene
      revealed conserved nature within CMLVs but considerable variability was observed
      between various species of OPVs. Most Indian CMLV isolates showed 99.5%-100% and
      96.3%-100% identity, at nucleotide (nt) and amino acid (aa) levels respectively,
      among themselves and with CMLV-M96 strain. Importantly, Indian CMLV strains along
      with CMLV-M96 showed deletion of seven nucleotides resulting in frameshift
      mutation at C-terminus of HA protein. Phylogenetic analysis displayed distinct
      clustering among CMLVs which might point to the circulation of diverse CMLV
      strains in nature. Despite different host specificity of OPVs, comparative
      sequence analysis of HA protein showed highly conserved N-terminal Ig V-set
      functional domain with tandem repeats. Understanding of molecular diversity of
      CMLVs and structural domains of HA protein will help in the elucidation of
      molecular mechanisms for immune evasion and design of novel antivirals for OPVs.

PMID- 30105895
TI  - Fracture resistance and survival of implant-supported, zirconia-based hybrid
      abutment crowns: Influence of aging and crown structure.
AB  - AIM: The aim of the present study was to investigate fracture resistance of
      implant-supported zirconia-based crowns (monolayer vs bilayer) cemented to hybrid
      abutments. METHODS: Monolayer and bilayer zirconia crowns were constructed and
      cemented to zirconia hybrid abutments. Crowns were divided into two subgroups:
      (a) untreated control group; and (b) experimental group, which underwent thermal
      cycling mechanical loading in a chewing simulator. Up to 1.2 million stress
      cycles with simultaneous thermocycling (5 and 55 degrees C) were applied. Samples
      were finally subjected to static load to fracture. Data were analyzed using one
      way analysis of variance and t test. Fractured surfaces were observed using
      scanning electron microscopy. RESULTS: Monolayer zirconia crowns had a 100%
      survival rate upon completion of the thermal mechanical loading, whereas bilayer
      zirconia crowns had a 50% survival rate. The fracture load of monolayer zirconia
      crowns was significantly higher than that of bilayer crowns. Moreover, the
      fracture load was significantly reduced in monolayer zirconia crowns after aging.
      Monolayer zirconia crowns showed bulk fracture within the monolayer, while
      bilayer crowns exhibited cohesive fracture within the veneering porcelain only.
      CONCLUSIONS: Monolayer implant-supported hybrid-abutment crowns exhibit
      significantly higher fracture resistance compared to bilayer crowns, making them
      better suited to handle higher masticatory loads encountered in the posterior
      region of the mouth.

PMID- 30105894
TI  - Intentions: The dynamic hierarchical model revisited.
AB  - Ten years ago, one of us proposed a dynamic hierarchical model of intentions that
      brought together philosophical work on intentions and empirical work on motor
      representations and motor control (Pacherie, 2008). The model distinguished among
      Distal intentions, Proximal intentions, and Motor intentions operating at
      different levels of action control (hence the name DPM model). This model
      specified the representational and functional profiles of each type of intention,
      as well their local and global dynamics, and the ways in which they interact. A
      core insight of the model was that action control is the result of integrated,
      coordinated activity across these levels of intention. Since the proposal of the
      model, empirical and theoretical works in philosophy and cognitive science have
      emerged that would seem to support and expand on this central insight. In
      particular, an updated understanding of the nature of sensorimotor processing and
      motor representations, as well as of how the different levels of intention and
      control interface and interact, allows for the further specification and
      precisification of the original DPM model. This article is categorized under:
      Philosophy > Psychological Capacities Psychology > Motor Skill and Performance
      Philosophy > Action.

PMID- 30105896
TI  - Ameloblastin attenuates RANKL-mediated osteoclastogenesis by suppressing
      activation of nuclear factor of activated T-cell cytoplasmic 1 (NFATc1).
AB  - Ameloblastin (Ambn) is an extracellular matrix protein and member of the family
      of enamel-related gene products. Like amelogenin, Ambn is mainly associated with
      tooth development, especially biomineralization of enamel. Previous studies have
      shown reductions in the skeletal dimensions of Ambn-deficient mice, suggesting
      that the protein also has effects on the differentiation of osteoblasts and/or
      osteoclasts. However, the specific pathways used by Ambn to influence osteoclast
      differentiation have yet to be identified. In the present study, two cellular
      models, one based on bone marrow cells and another on RAW264.7 cells, were used
      to examine the effects of Ambn on receptor activator of nuclear factor kappa-B
      ligand (RANKL)-induced osteoclastogenesis. The results showed that Ambn
      suppresses osteoclast differentiation, cytoskeletal organization, and osteoclast
      function by the downregulation of the number of tartrate-resistant acid
      phosphatase (TRAP)-positive multinucleated osteoclasts, actin ring formation, and
      areas of pit resorption. The expression of the osteoclast-specific genes TRAP,
      MMP9, cathepsin K, and osteoclast stimulatory transmembrane protein (OC-STAMP)
      was abolished in the presence of Ambn, while that of nuclear factor of activated
      T cells cytoplasmic 1 (NFATc1), the master regulatory factor of
      osteoclastogenesis, was also attenuated by the downregulation of c-Fos
      expression. In Ambn-induced RAW264.7 cells, phosphorylation of cAMP-response
      element-binding protein (CREB), c-Jun N-terminal kinase (JNK), and p38 mitogen
      activated protein kinase (p38 MAPK), but not extracellular signal-regulated
      kinase 1/2 (ERK1/2), was reduced. Calcium oscillation was also decreased in the
      presence of Ambn, suggesting its involvement in both RANKL-induced
      osteoclastogenesis and costimulatory signaling. B-lymphocyte-induced maturation
      protein-1 (Blimp1), a transcriptional repressor of negative regulators of
      osteoclastogenesis, was also downregulated by Ambn, resulting in the elevated
      expression of v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B
      (MafB), B-cell lymphoma 6 (Bcl6), and interferon regulatory factor-8 (Irf8).
      Taken together, these findings suggest that Ambn suppresses RANKL-induced
      osteoclastogenesis by modulating the NFATc1 axis.

PMID- 30105897
TI  - Leukemia in gastrointestinal organs as cause of treatment failure: 378 cases
      analyzed.
AB  - Leukemia growing as tumors in gastrointestinal organs is an under-investigated
      cause of treatment failure and death. These present with symptoms often mistaken
      for common toxicities but may grow large before symptoms. To synthesize
      experience available only in case reports, 378 were analyzed. Invasive and
      metastatic behavior typical of solid GI tumors was revealed even when marrow was
      uninvolved. Within 3 months of diagnosis, 33% had died, 47% within 1 year.
      Survivals of 4 to 18 years after involvement suggest cure is possible. Evidence
      is presented that combined local and systemic therapy has successfully treated GI
      leukemic tumors when identified early.

PMID- 30105898
TI  - The Intersection of Residence, Community Vulnerability, and Premature Mortality.
AB  - PURPOSE: Rural communities often experience higher rates of mortality than their
      urban counterparts, with gaps widening in the foreseeable future. However, the
      underlying level of socioeconomic vulnerability (area deprivation) among rural
      communities can vary widely. This study examines rural-urban differences in
      mortality-related outcomes within comparable levels of deprivation. METHODS:
      Rural-urban differences in Years of Potential Life Lost (YPLL), derived from the
      County Health Rankings, were examined across comparable levels of area
      deprivation using a quantile regression approach. Rural-urban differences in YPLL
      were estimated at the 10th, 25th, 50th, 75th, and 90th percentiles across levels
      of deprivation. FINDINGS: Compared to the reference population (urban
      counties/least deprived) a clear increase in YPLL among both rural and urban
      counties was noted across levels of deprivation, with the highest level of YPLL
      occurring in counties with the most deprivation. While YPLL increased across
      levels of deprivation, the magnitude of these differences was markedly higher in
      rural counties compared to urban, particularly among the most deprived counties.
      Rural counties experienced an advantage at the lowest percentiles and levels of
      deprivation. However, this advantage quickly deteriorated, revealing significant
      rural disparities at the highest level of deprivation. CONCLUSIONS: This study
      noted a differential effect in mortality-related outcomes among rural counties
      within comparable levels of community deprivation. Findings contribute to
      evidence that many, but not all rural communities face a double disadvantage.
      This underscores the need for a continued focus on the development and
      implementation of multiple policies aimed at reducing differences in poverty,
      education, and access to care.

PMID- 30105899
TI  - Ward culture and staff relationships at hospital mealtimes in Australia: An
      ethnographic account.
AB  - Nutrition care is a fundamental component of quality health care provided to
      patients in hospital, yet little is known about the staff who deliver this care
      and their interrelationships, and how this impacts nutrition care. In this
      ethnographic study on two subacute wards, 67 h of fieldwork was conducted over 3
      months to explore the relationships, roles, and responsibilities of those
      involved at mealtimes, and the influence on meal provision. Data were analyzed
      inductively and thematically. Three themes describing ward culture and staff
      relationships emerged: (i) defining mealtime roles and maintaining boundaries;
      (ii) balancing the need for teamwork and having time and space; and (iii)
      effective communication supports role completion and problem solving. Lack of
      appreciation of workflow enablers and barriers degraded working relationships
      between staff with and without central roles at mealtimes. The present study
      informs health-care organizations on building a culture that supports
      interprofessional collaboration in nutrition care in the subacute setting. All
      staff need to be aware of their and others' mealtime roles and responsibilities
      to support a coordinated approach.

PMID- 30105902
TI  - Ultrasensitive and Fully Reversible NO2 Gas Sensing Based on p-Type MoTe2 under
      Ultraviolet Illumination.
AB  - The unique properties of two-dimensional (2D) materials make them promising
      candidates for chemical and biological sensing applications. However, most 2D
      material sensors suffer from extremely long recovery time due to the slow
      molecular desorption at room temperature. Here, we report an ultrasensitive p
      type molybdenum ditelluride (MoTe2) gas sensor for NO2 detection with greatly
      enhanced sensitivity and recovery rate under ultraviolet (UV) illumination.
      Specifically, the sensitivity of the sensor to NO2 is dramatically enhanced by 1
      order of magnitude under 254 nm UV illumination as compared to that in the dark
      condition, leading to a remarkable low detection limit of 252 ppt. More
      importantly, the p-type MoTe2 sensor can achieve full recovery after each sensing
      cycle well within 160 s at room temperature. Finally, the p-type MoTe2 sensor
      also exhibits excellent sensing performance to NO2 in ambient air and negligible
      response to H2O, indicating its great potential in practical applications, such
      as breath analysis and ambient NO2 detection. Such impressive features originate
      from the activated interface interaction between the gas molecules and p-type
      MoTe2 surface under UV illumination. This work provides a promising and easily
      applicable strategy to improve the performance of the gas sensors based on 2D
      materials.

PMID- 30105901
TI  - PGC-1alpha in hepatic UPR during high-fat high-fructose diet and exercise
      training in mice.
AB  - Diet-induced obesity is associated with hepatic steatosis, which has been linked
      with activation of the unfolded protein response (UPR). PGC-1alpha is a
      transcriptional coactivator involved in exercise training-induced adaptations in
      muscle and liver. Therefore, the aim of this study was to test the hypothesis
      that PGC-1alpha is required for exercise training-mediated prevention of diet
      induced steatosis and UPR activation in liver. Male liver-specific PGC-1alpha
      knockout (LKO) and littermate floxed (lox/lox) mice were divided into two groups
      receiving either control diet (CON) or high-fat high-fructose diet (HFF). After 9
      weeks, half of the HFF mice were treadmill exercise trained for 4 weeks
      (HFF+ExT), while the rest were kept sedentary. HFF resulted in increased body and
      liver weight, adiposity, hepatic steatosis and whole body glucose intolerance as
      well as decreased hepatic IRE1alpha phosphorylation. Exercise training prevented
      the HFF-induced weight gain and partially prevented increased liver weight,
      adiposity and glucose intolerance, but with no effect on liver triglycerides. In
      addition, BiP protein and CHOP mRNA content increased with exercise training
      compared with CON and HFF, respectively. Lack of PGC-1alpha in the liver only
      resulted in minor changes in the PERK pathway. In conclusion, this study provides
      evidence for dissociation between diet-induced hepatic triglyceride accumulation
      and hepatic UPR activation. In addition, PGC-1alpha was not required for
      maintenance of basal UPR in the liver and due to only minor exercise training
      effects on UPR further studies are needed to conclude on the potential role of
      PGC-1alpha in exercise training-induced adaptations in hepatic UPR.

PMID- 30105900
TI  - Insight into metabolic diversity of the brown-rot basidiomycete Postia placenta
      responsible for sesquiterpene biosynthesis: semi-comprehensive screening of
      cytochrome P450 monooxygenase involved in protoilludene metabolism.
AB  - A wide variety of sesquiterpenoids have been isolated from basidiomycetes, and
      their bioactive properties have attracted significant attention in an effort to
      understand biosynthetic machineries. As both sesquiterpene synthases and
      cytochrome P450 monooxygenases play key roles in the diversification of
      sesquiterpenoids, it is important to widely and mutually understand their
      biochemical properties. In this study, we performed genome-wide annotation and
      functional characterization of sesquiterpene synthases from the brown-rot
      basidiomycete Postia placenta. Using RT-PCR, we isolated 16 sesquiterpene
      synthases genes as full-length cDNAs. Heterologous expression revealed that the
      sesquiterpene synthases could produce a series of sesquiterpene scaffolds with
      distinct metabolic profiles. Based on metabolic studies, we identified 25
      sesquiterpene scaffolds including Delta6-protoilludene produced by the
      sesquiterpene synthases. In particular, a protoilludene synthase from the brown
      rot basidiomycete was characterized for the first time. Furthermore, we conducted
      a semi-comprehensive functional screening of cytochrome P450 monooxygenases from
      P. placenta to elucidate biosynthetic machineries involved in metabolisms of
      Delta6-protoilludene. Coexpression of protoilludene synthase and 184 isoforms of
      cytochrome P450 monooxygenases enabled the identification of CYP5344B1, CYP5348E1
      and CYP5348J3, which catalysed the hydroxylation reaction of Delta6-protoilludene
      to produce Delta6-protoilludene-8-ol and Delta6-protoilludene-5-ol. Furthermore,
      structural isomers of Delta7-protoilludene-6-ol were obtained from incubation of
      Delta6-protoilludene-8-ol in acidic culture medium.

PMID- 30105903
TI  - The Recombinant and Reconstituted Novel Albumin-Lidamycin Conjugate Shows Lasting
      Tumor Imaging and Intensively Enhanced Therapeutic Efficacy.
AB  - Depending on increasing extracellular protein utilization and altering metabolic
      programs, cancer cells could proliferate and survive without restricion by
      ingesting human serum albumin (HSA) to serve as nutritional amino acids. Here, we
      hypothesize that the consumption of albumin by cancer cells could be utilized as
      an efficient approach to targeted drug delivery. Lidamycin (LDM), an antitumor
      antibiotic with extremely potent cytotoxicity to cultured cancer cells, consists
      of an apoprotein (LDP) and an active enediyne chromophore (AE). In the present
      study, a novel albumin-lidamycin conjugate was prepared by DNA recombination and
      molecular reconstitution. Results show that the IC50 values of albumin-lidamycin
      conjugate (HSA-LDP-AE) for a variety of tested cancer cells were at subnanomolar
      levels. At tolerated doses, the albumin-lidamycin conjugate significantly
      inhibited the growth of lung carcinoma PG-BE1 xenografts by 97.8%. The
      therapeutic efficacy of the albumin-lidamycin conjugate was much stronger than
      that of free lidamycin. Meanwhile, the images of albumin-lidamycin conjugate
      showed obvious and lasting tumor localization and fluorescence enrichment and
      there was no detectable signal in nontumor locations. Taken together, albumin
      lidamycin conjugate, a new format of lidamycin, could be a promising antitumor
      therapeutic agent and albumin-integration might be a feasible approach to
      targeted antitumor drug delivery.

PMID- 30105904
TI  - Manipulating Behaviors from Heavy Tungsten Doping on Interband Electronic
      Transition and Orbital Structure Variation of Vanadium Dioxide Films.
AB  - Vanadium dioxide (VO2) with a metal-insulator transition (MIT) has been supposed
      as a candidate for optoelectronic devices. However, the MIT temperature ( TMIT)
      above room temperature limits its application scope. Here, high-quality V1- xW
      xO2 films have been prepared by pulsed laser deposition. On the basis of
      temperature-dependent transmittance and Raman spectra, it was found that TMIT
      increases from 241 to 279 K, when increasing the doping concentration in the
      range of 0.16 <= x <= 0.20. The interband electronic transitions and orbital
      structures of V1- xW xO2 films have been investigated via fitting transmittance
      spectra. Moreover, with the aid of first-principles calculations, an effective
      orbital theory has been proposed to explain the unique phenomenon. When the W
      doping concentration increases, the pi* and dII orbitals shift toward the pi
      orbital. Meanwhile, the energy gap between the pi* and dII orbitals decreases at
      the insulator state. It indicates that the bandwidth is narrowed, which impedes
      MIT. In addition, the overlap of the pi* and dII orbitals increases at the metal
      state, and more doping electrons occupy the pi* orbital induced by increasing W
      doping concentration. It manifests that the Mott insulating state becomes more
      stable, which further improves TMIT. The present work provides a feasible
      approach to tune TMIT via orbital variation and can be helpful in developing the
      potential VO2-based optoelectronic devices.

PMID- 30105905
TI  - Genuinely Ferroelectric Sub-1-Volt-Switchable Nanodomains in Hf xZr(1- x)O2
      Ultrathin Capacitors.
AB  - The new class of fully silicon-compatible hafnia-based ferroelectrics with high
      switchable polarization and good endurance and thickness scalability shows a
      strong promise for new generations of logic and memory devices. Among other
      factors, their competitiveness depends on the power efficiency that requires
      reliable low-voltage operation. Here, we show genuine ferroelectric switching in
      Hf xZr(1- x)O2 (HZO) layers in the application-relevant capacitor geometry, for
      driving signals as low as 800 mV and coercive voltage below 500 mV. Enhanced
      piezoresponse force microscopy with sub-picometer sensitivity allowed for probing
      individual polarization domains under the top electrode and performing a detailed
      analysis of hysteretic switching. The authentic local piezoelectric loops and
      domain wall movement under bias attest to the true ferroelectric nature of the
      detected nanodomains. The systematic analysis of local piezoresponse loop arrays
      reveals a totally unexpected thickness dependence of the coercive fields in HZO
      capacitors. The thickness decrease from 10 to 7 nm is associated with a
      remarkably strong decrease of the coercive field, with about 50% of the capacitor
      area switched at coercive voltages <=0.5 V. Our explanation consistent with the
      experimental data involves a change of mechanism of nuclei-assisted switching
      when the thickness decreases below 10 nm. The practical implication of this
      effect is a robust ferroelectric switching under the millivolt-range driving
      signal, which is not expected for the standard coercive voltage scaling law.
      These results demonstrate a strong potential for further aggressive thickness
      reduction of HZO layers for low-power electronics.

PMID- 30105906
TI  - Chemically Modified Hydrogel-Filled Nanopores: A Tunable Platform for Single
      Molecule Sensing.
AB  - Label-free, single-molecule sensing is anideal candidate for biomedical
      applications that rely on the detection of low copy numbers in small volumes and
      potentially complex biofluids. Among them, solid-state nanopores can be
      engineered to detect single molecules of charged analytes when they are
      electrically driven through the nanometer-sized aperture. When successfully
      applied to nucleic acid sensing, fast transport in the range of 10-100
      nucleotides per nanosecond often precludes the use of standard nanopores for the
      detection of the smallest fragments. Herein, hydrogel-filled nanopores (HFN) are
      reported that combine quartz nanopipettes with biocompatible chemical poly(vinyl)
      alcohol hydrogels engineered in-house. Hydrogels were modified physically or
      chemically to finely tune, in a predictable manner, the transport of specific
      molecules. Controlling the hydrogel mesh size and chemical composition allowed us
      to slow DNA transport by 4 orders of magnitude and to detect fragments as small
      as 100 base pairs (bp) with nanopores larger than 20 nm at an ionic strength
      comparable to physiological conditions. Considering the emergence of cell-free
      nucleic acids as blood biomarkers for cancer diagnostics or prenatal testing, the
      successful sensing and size profiling of DNA fragments ranging from 100 bp to >1
      kbp long under physiological conditions demonstrates the potential of HFNs as a
      new generation of powerful and easily tunable molecular diagnostics tools.

PMID- 30105907
TI  - Spin-Conserving Resonant Tunneling in Twist-Controlled WSe2-hBN-WSe2
      Heterostructures.
AB  - We investigate interlayer tunneling in heterostructures consisting of two
      tungsten diselenide (WSe2) monolayers with controlled rotational alignment, and
      separated by hexagonal boron nitride. In samples where the two WSe2 monolayers
      are rotationally aligned we observe resonant tunneling, manifested by a large
      conductance and negative differential resistance in the vicinity of zero
      interlayer bias, which stem from energy- and momentum-conserving tunneling.
      Because the spin-orbit coupling leads to coupled spin-valley degrees of freedom,
      the twist between the two WSe2 monolayers allows us to probe the conservation of
      spin-valley degree of freedom in tunneling. In heterostructures where the two
      WSe2 monolayers have a 180 degrees  relative twist, such that the Brillouin zone
      of one layer is aligned with the time-reversed Brillouin zone of the opposite
      layer, the resonant tunneling between the layers is suppressed. These findings
      provide evidence that, in addition to momentum, the spin-valley degree of freedom
      is also conserved in vertical transport.

PMID- 30105908
TI  - Streptococcus pneumoniae Sialidase SpNanB-Catalyzed One-Pot Multienzyme (OPME)
      Synthesis of 2,7-Anhydro-Sialic Acids as Selective Sialidase Inhibitors.
AB  - Streptococcus pneumoniae sialidase SpNanB is an intramolecular trans-sialidase
      (IT-sialidase) and a virulence factor that is essential for streptococcal
      infection of the upper and lower respiratory tract. SpNanB catalyzes the
      formation of 2,7-anhydro- N-acetylneuraminic acid (2,7-anhydro-Neu5Ac), a
      potential prebiotic that can be used as the sole carbon source of a common human
      gut commensal anaerobic bacterium. We report here the development of an efficient
      one-pot multienzyme (OPME) system for synthesizing 2,7-anhydro-Neu5Ac and its
      derivatives. Based on a crystal structure analysis, an N-cyclohexyl derivative of
      2,7-anhydro-neuraminic acid was designed, synthesized, and shown to be a
      selective inhibitor against SpNanB and another Streptococcus pneumoniae sialidase
      SpNanC. This study demonstrates a new strategy of synthesizing 2,7-anhydro-sialic
      acids in a gram scale and the potential application of their derivatives as
      selective sialidase inhibitors.

PMID- 30105909
TI  - Artificial Synaptic Emulators Based on MoS2 Flash Memory Devices with Double
      Floating Gates.
AB  - We fabricated MoS2-based flash memory devices by stacking MoS2 and hexagonal
      boron nitride (hBN) layers on an hBN/Au substrate and demonstrated that these
      devices can emulate various biological synaptic functions, including potentiation
      and depression processes, spike-rate-dependent plasticity, and spike-timing
      dependent plasticity. In particular, compared to a flash memory device prepared
      on an hBN substrate, the device fabricated on the hBN/Au exhibited considerably
      more symmetric and linear bidirectional gradual conductance change curves, which
      may be attributed to the device structure incorporating double floating gate. For
      the device on the hBN/Au, electron transfers may occur between the floating gate
      MoS2 and Au, as well as between the floating gate MoS2 and the channel MoS2,
      allowing for more control over electron tunneling and injection. To test our
      hypothesis, we also fabricated a MoS2-based flash memory device on an hBN/Pd
      substrate and found behavior similar to the device fabricated on hBN/Au. Our
      results demonstrate that flexible synaptic electronics may be implemented using
      MoS2-based flash memory devices with double floating gates.

PMID- 30105910
TI  - Synthesis of Highly Enantioenriched Propelladienes and their Application as
      Ligands in Asymmetric Rh-Catalyzed 1,4-Additions.
AB  - The first synthesis of highly enantioenriched [4.3.3]propelladienes is reported.
      The novel bridged bicyclo[3.3.0] dienes were applied as steering ligands in the
      rhodium-catalyzed asymmetric arylation of cyclic enones. The catalytic system
      showed high catalytic activity, and the 1,4-adducts were obtained in good to
      excellent yields (46-99%) with enantioselectivities up to 96% ee.

PMID- 30105911
TI  - Rapid Detection of Drugs in Human Plasma Using a Small-Molecule-Linked
      Hybridization Chain Reaction.
AB  - Rapid detection and quantification of pharmaceutical drugs directly in human
      plasma is of major importance for the development of relevant point-of-care
      testing devices. Here, we report a method for detection and quantification of
      small molecules in human plasma. An assay employing a small molecule-linked
      hybridization chain reaction (HCR) has been devised for the detection of the
      pharmaceutically relevant drugs digoxin (Dig) and methotrexate (MTX). Double
      modification by small molecule ligands on the initiator strand act as sites to
      control the rate of the HCR. Upon protein binding to the modified initiator
      strand, the HCR is greatly inhibited. If the protein is preincubated with a
      sample containing the small molecule analyte, the protein binding site is
      occupied by the analyte and the initiator strand will initiate the HCR. This
      enables efficient detection and quantification of small-molecule analytes in
      nanomolar concentration even in 50% human plasma within 4 min. Thus, the rapidity
      and simplicity of this assay has potential for point-of-care testing.

PMID- 30105912
TI  - Single Low-Dose Injection of Evans Blue Modified PSMA-617 Radioligand Therapy
      Eliminates Prostate-Specific Membrane Antigen Positive Tumors.
AB  - Prostate cancer is the most frequently diagnosed malignant tumor in men
      worldwide. Prostate-specific membrane antigen (PSMA) is a surface molecule
      specifically expressed by prostate tumors that has been shown to be a valid
      target for internal radionuclide therapy in both preclinical and clinical
      settings. The most common radiotherapeutic agent is the small molecule 177Lu-PSMA
      617, which is under clinical evaluation in multiple countries. Nevertheless, its
      efficacy in causing tumor regression is still suboptimal, even when administered
      in several cycles per patient, perhaps due to poor pharmacokinetics (PK), which
      limits uptake by the tumor cells. We postulated that the addition of the Evans
      blue (EB) moiety to PSMA-617 would improve the PK by extending circulation half
      life, which would increase tumor uptake and improve radiotherapeutic efficacy.
      PSMA-617 was modified by conjugation of a 2-thiol acetate group onto the primary
      amine and thereafter reacted with a maleimide functional group of an EB
      derivative, to give EB-PSMA-617. The PK and radiotherapeutic efficacy of 90Y- or
      177Lu-EB-PSMA-617 was compared to the clinically used radiopharmaceutical 90Y- or
      177Lu- PSMA-617 in PC3-PIP tumor-bearing mice. EB-PSMA-617 retained binding to
      serum albumin as well as a high internalization rate by tumor cells. Upon
      injection, metal-labeled EB-PSMA-617 demonstrated an extended blood half-life
      compared to PSMA-617 and, thereby, prolonged the time window for binding to PSMA.
      The improved PK of EB-PSMA-617 resulted in significantly higher accumulation in
      PSMA+ tumors and highly effective radiotherapeutic efficacy. Remarkably, a single
      dose of 1.85 MBq of 90Y- or 177Lu-EB-PSMA-617 was sufficient to eradicate
      established PMSA+ tumors in mice. No significant body weight loss was observed,
      suggesting little to no gross toxicity. The construct described here, EB-PSMA
      617, may improve the radiotherapeutic efficacy for patients with PSMA-positive
      tumors by reducing both the amount of activity needed for therapy as well as the
      frequency of administration, as compared to PSMA-617.

PMID- 30105913
TI  - Exploring Activity Profiles of PAINS and Their Structural Context in Target
      Ligand Complexes.
AB  - Assay interference is an acknowledged problem in high-throughput screening, and
      pan-assay interference compounds (PAINS) filters are one of a number of
      approaches that have been suggested for identification of potential screening
      artifacts or frequent hitters. Many studies have highlighted that the unwary
      usage of these structural alerts should be reconsidered and criticized their
      extrapolation beyond the applicability domain. A large-scale investigation of the
      activity profiles and the structural context of PAINS might provide a better
      assessment of whether this extrapolation is valid. To this end, multiple publicly
      accessible compound collections were screened, and the PAINS statistics are
      comprehensively presented and discussed. Next, the promiscuity trends and
      activity profiles of PAINS were compared with those compounds not matching any
      PAINS substructures. Overall, PAINS demonstrated higher promiscuity and
      relatively higher assay hit rates compared with the other compounds. Furthermore,
      nearly 2000 distinct target-ligand complexes containing PAINS were analyzed, and
      the interactions were quantified and compared. In more than 50% of the instances,
      the PAINS atoms participated in interactions more frequently compared with the
      remaining atoms of the ligand structure. Many PAINS participated in crucial
      interactions that were often responsible for binding of the ligand, which
      reaffirms their distinction from those responsible for assay interference. In
      conclusion, we reinforce that while it is important to employ compound filters to
      eliminate nonspecific hits, establishing a set of statistically significant and
      validated PAINS filters is essential to restrain the black-box practice of
      triaging screening hits matching any of the proposed 480 alerts.

PMID- 30105914
TI  - Association of BMI Changes Between Adolescence and Young Adulthood With Smoking
      Cessation.
AB  - PURPOSE: Weight gain frequently accompanies smoking cessation. This study
      examined if increasing body mass index (BMI) during the early years of smoking
      influences quitting by young adulthood. DESIGN: Longitudinal, observational study
      using in-home interview data. SETTING: National Longitudinal Study of Adolescent
      and Adult Health (Add Health) 1994 to 2008. SUBJECTS: Nine hundred forty-nine
      adolescent smokers (12-19 years) followed into young adulthood (20-32 years)
      through 4 waves of in-home interviews. MEASURES: Outcome variable: Young adult
      smoking status (yes or no) reported at in-home interviews. FACTORS: Gender and 4
      longitudinal adolescent/young adult BMI trajectories-normal/normal,
      normal/overweight, normal/obese, and overweight/obese. Covariates: Race
      ethnicity, education, household income, and recent quit attempt in adolescence.
      ANALYSIS: Binary logistic regression analysis. RESULTS: Overall, the rate at
      which young adults quit smoking was not significantly different based on gender.
      However, longitudinal changes in BMI trajectory and gender interact to influence
      young adult smoking status. Women having normal/overweight and normal/obese BMI
      trajectories were less likely to quit smoking than men. Odds that young adults
      having some college or post-high school education quit smoking were greater than
      those with high school education or less. CONCLUSION: At a minimum, providing
      direct information regarding anticipated weight changes after quitting is
      indicated in smoking cessation intervention, in addition to strategies to
      mitigate postcessation weight gain. Faced with weight gain, younger smokers,
      particularly women, may be more resistant to quitting smoking.

PMID- 30105915
TI  - Treatment Complexities Among Patients with Tuberculosis in a High HIV Prevalence
      Cohort in the United States.
AB  - The association between human immunodeficiency virus (HIV) infection and
      tuberculosis (TB) mortality has been studied extensively, but the impact of HIV
      on other clinically relevant aspects of TB care such as TB drug-related adverse
      events (AEs), hospital readmissions, and TB treatment duration is less well
      characterized. We describe the association of HIV infection with TB clinical
      complexities and outcomes in a high HIV prevalence cohort in the United States.
      This is a retrospective cohort study among patients treated for culture-confirmed
      TB between 2008 and 2015 at an inner-city hospital in Atlanta, GA. Univariate
      analysis was used to estimate association of HIV with TB treatment interruption
      due to AEs, hospital readmissions, and treatment duration. Final unfavorable TB
      treatment outcome was defined as death, loss to follow-up, or recurrent TB.
      Logistic regression modeling was used to estimate association of HIV with final
      unfavorable outcomes. Among 274 patients with TB, 96 (35%) had HIV coinfection.
      HIV-positive patients had more TB treatment interruptions due to AE (34% vs.
      15%), were more likely to have a hospital readmission (50% vs. 21%), and received
      longer TB treatment (9.9 months vs. 8.8 months) compared to HIV-negative patients
      (p < .01 for all). HIV infection was not associated with final unfavorable
      outcomes in univariate [odds ratio (OR) = 1.86; confidence interval (95% CI) 0.99
      3.49] or multivariate analysis (aOR = 1.13; 95% CI 0.52-2.39) (p >= .05 for
      both). While HIV infection was not associated with final unfavorable TB outcomes,
      TB/HIV coinfected patients had more complex treatment course underscoring the
      importance of maintaining resources and expertise to treat coinfected patients in
      our and similar settings.

PMID- 30105916
TI  - A Summary of the Third Annual HIV Microbiome Workshop.
AB  - Our microbial cotravelers have increasingly apparent roles in both maintaining
      health and causing disease in several organ systems. Investigators gather
      annually at the National Institutes of Health to present new discoveries
      regarding the role of the microbiome in human health and a special focus on
      persons living with HIV. Here, we summarize the discussions from the third annual
      Virology Education workshop on the microbiome in HIV, which took place in October
      of 2017.

PMID- 30105917
TI  - Adaptor Protein p66Shc: A Link Between Cytosolic and Mitochondrial Dysfunction in
      the Development of Diabetic Retinopathy.
AB  - AIMS: Diabetes increases oxidative stress in the retina and dysfunctions their
      mitochondria, accelerating capillary cell apoptosis. A 66 kDa adaptor protein,
      p66Shc, is considered as a sensor of oxidative stress-induced apoptosis. In the
      pathogenesis of diabetic retinopathy, a progressive disease, reactive oxygen
      species (ROS) production by activation of a small molecular weight G-protein (Ras
      related C3 botulinum toxin substrate 1 [Rac1])-Nox2 signaling precedes
      mitochondrial damage. Rac1 activation is facilitated by guanine exchange factors
      (GEFs), and p66Shc increases Rac1-specific GEF activity of Son of Sevenless 1
      (Sos1). p66Shc also possesses oxidoreductase activity and can directly stimulate
      mitochondrial ROS generation. Our aim was to investigate the role of p66Shc in
      the development of diabetic retinopathy and mechanism of its transcription.
      RESULTS: High glucose increased p66Shc expression in human retinal endothelial
      cells, and elevated acetylated histone 3 lysine 9 (H3K9) levels and
      transcriptional factor p53 binding at its promoter. Glucose also augmented
      interactions between Rac1 and Sos1 and activated Rac1-Nox2. Phosphorylation of
      p66Shc was increased, allowing it to interact with peptidyl prolyl isomerase to
      facilitate its localization inside the mitochondria, culminating in mitochondrial
      damage. P66shc-small interfering RNA (siRNA) inhibited glucose-induced Rac1
      activation and mitochondrial damage. Similar results are observed in retinal
      microvessels from diabetic rats. INNOVATION: This is the first report identifying
      the role of p66Shc in the development of diabetic retinopathy and implicating
      increased histone acetylation in its transcriptional regulation. CONCLUSION:
      Thus, p66Shc has dual role in the development of diabetic retinopathy; its
      regulation in the early stages of the disease should impede Rac1-ROS production
      and, in the later stages, prevent mitochondrial damage and initiation of a futile
      cycle of free radicals. Antioxid. Redox Signal. 00, 000-000.

PMID- 30105918
TI  - Sodium stibogluconate loaded nano-deformable liposomes for topical treatment of
      leishmaniasis: macrophage as a target cell.
AB  - Topical drug delivery against cutaneous leishmaniasis (CL) signifies an effective
      alternate for improving the availability and reducing the toxicity associated
      with the parenteral administration of conventional sodium stibogluconate (SSG)
      injection. The basic aim of the study was to develop nano-deformable liposomes
      (NDLs) for the dermal delivery of SSG against CL. NDLs were formulated by a
      modified thin film hydration method and optimized via Box-Behnken statistical
      design. The physicochemical properties of SSG-NDLs were established in terms of
      vesicle size (195.1 nm), polydispersity index (0.158), zeta potential (-32.8 mV),
      and entrapment efficiency (35.26%). Moreover, deformability index, in vitro
      release, and macrophage uptake studies were also accomplished. SSG-NDLs were
      entrapped within Carbopol gel network for the ease of skin application. The ex
      vivo skin permeation study revealed that SSG-NDLs gel provided 10-fold higher
      skin retention towards the deeper skin layers, attained without use of classical
      permeation enhancers. Moreover, in vivo skin irritation and histopathological
      studies verified safety of the topically applied formulation. Interestingly, the
      cytotoxic potential of SSG-NDLs (1.3 mg/ml) was higher than plain SSG (1.65
      mg/ml). The anti-leishmanial activity on intramacrophage amastigote model of
      Leishmania tropica showed that IC50 value of the SSG-NDLs was ~ fourfold lower
      than the plain drug solution with marked increase in the selectivity index. The
      in vivo results displayed higher anti-leishmanial activity by efficiently healing
      lesion and successfully reducing parasite burden. Concisely, the outcomes
      indicated that the targeted delivery of SSG could be accomplished by using
      topically applied NDLs for the effective treatment of CL.

PMID- 30105919
TI  - Surgical Management of Normocalcemic Primary Hyperparathyroidism and the Impact
      of Intraoperative Parathyroid Hormone Testing on Outcome.
AB  - Objective To review our surgical experience and the impact of intraoperative
      parathyroid hormone (IOPTH) testing among patients with normocalcemic primary
      hyperparathyroidism. Study Design Case series with chart review. Setting Academic
      referral hospital. Subject and Methods Normocalcemic hyperparathyroidism (NCHPT)
      patients were identified with normal-range blood ionized calcium and serum
      elevated parathyroid hormone. Patient demographics, intraoperative findings,
      IOPTH dynamics, and biochemical outcomes were compared with those of classic
      primary hyperparathyroidism (PHPT) patients. Results Of the 2120 patients who
      underwent parathyroidectomy, 616 patients met the inclusion criteria: 119 (19.5%)
      patients had NCHPT, and 497 (80.5%) had classic PHPT. NCHPT patients had higher
      rates of multigland hyperplasia as compared with classic PHPT (12% vs 4%, P =
      .002) and smaller gland size ( P < .001). Of 119 NCHPT patients, 114 (97%)
      achieved >50% drop in IOPTH intraoperatively, as opposed to 492 (99%) among 497
      classic PHPT patients ( P = .014). IOPTH drop >50% had an equivalent positive
      predictive value for long-term cure in both groups. Conclusions Surgeons treating
      NCHPT patients should suspect the presence of multigland disease and have a low
      threshold for converting to bilateral exploration depending on IOPTH decay
      dynamics.

PMID- 30105920
TI  - A Dynamic Window Recognition Algorithm for SSVEP-Based Brain-Computer Interfaces
      Using a Spatio-Temporal Equalizer.
AB  - The past decade has witnessed rapid development in the field of brain-computer
      interfaces (BCIs). While the performance is no longer the biggest bottleneck in
      the BCI application, the tedious training process and the poor ease-of-use have
      become the most significant challenges. In this study, a spatio-temporal
      equalization dynamic window (STE-DW) recognition algorithm is proposed for steady
      state visual evoked potential (SSVEP)-based BCIs. The algorithm can adaptively
      control the stimulus time while maintaining the recognition accuracy, which
      significantly improves the information transfer rate (ITR) and enhances the
      adaptability of the system to different subjects. Specifically, a spatio-temporal
      equalization algorithm is used to reduce the adverse effects of spatial and
      temporal correlation of background noise. Based on the theory of multiple
      hypotheses testing, a stimulus termination criterion is used to adaptively
      control the dynamic window. The offline analysis which used a benchmark dataset
      and an offline dataset collected from 16 subjects demonstrated that the STE-DW
      algorithm is superior to the filter bank canonical correlation analysis (FBCCA),
      canonical variates with autoregressive spectral analysis (CVARS), canonical
      correlation analysis (CCA) and CCA reducing variation (CCA-RV) algorithms in
      terms of accuracy and ITR. The results show that in the benchmark dataset, the
      STE-DW algorithm achieved an average ITR of 134 bits/min, which exceeds the
      FBCCA, CVARS, CCA and CCA-RV. In off-line experiments, the STE-DW algorithm also
      achieved an average ITR of 116 bits/min. In addition, the online experiment also
      showed that the STE-DW algorithm can effectively expand the number of applicable
      users of the SSVEP-based BCI system. We suggest that the STE-DW algorithm can be
      used as a reliable identification algorithm for training-free SSVEP-based BCIs,
      because of the good balance between ease of use, recognition accuracy, ITR and
      user applicability.

PMID- 30105921
TI  - Clinical implications of selective serotonin reuptake inhibitors-selective
      serotonin norepinephrine reuptake inhibitors pharmacogenetics during pregnancy
      and lactation.
AB  - Depression occurs during pregnancy in 3.9-12.8% of the women. The different
      serotonin reuptake inhibitors (SRIs) are metabolized in the liver by CYP450
      enzymes. CYP2D6 metabolizes paroxetine, fluoxetine, duloxetine and venlafaxine,
      while CYP2C19 deactivates citalopram and escitalopram. Polymorphisms in these
      enzymes change the metabolic clearance and levels of these drugs. Higher
      metabolism of most SRIs in late pregnancy results in lower maternal levels, which
      could result in decreased efficacy. Very few studies have addressed the potential
      interaction between pregnancy-induced increase in 2D6 metabolism and specific
      genotypes of the women, suggesting that ultra-rapid and extensive metabolizers
      exhibit lower serum concentrations than the other slower genotypes. Preliminary
      studies suggest that some genotypes of the serotonin transporter (SLC6A4)
      promoter are associated and are linked to adverse effects in infants with SRI
      exposure during pregnancy. Presently, there are no clear clinical implications of
      SRI pharmacogenetic status in pregnancy and lactation. In late pregnancy, women
      may exhibit lower steady state concentrations of these drugs, necessitating
      increased doses but these are presently guided clinically and not through
      genotyping. Much more work is needed to define whether SRI genotype has clinical
      implications and predictive value for either mother or offspring.

PMID- 30105922
TI  - Clinical Significance of Sarcopenia among Patients with Advanced Oropharyngeal
      Cancer.
AB  - Objectives We investigated the prevalence and impact of sarcopenia on disease
      free survival (DFS) and overall survival (OS) in advanced oropharyngeal cancer.
      Study Design Retrospective study. Setting Single-institution tertiary cancer care
      center. Subjects and Methods We identified patients with advanced oropharyngeal
      cancer with pretreatment positron emission tomography-computed tomography scans
      for image analysis. Data were collected on the following variables: age, sex,
      smoking and alcohol status, stage (TNM and American Joint Committee on Cancer),
      human papillomavirus (HPV) status, body mass index (BMI), and treatment modality.
      Results Of 113 patients identified with oropharyngeal cancer, 32 had sarcopenia:
      these patients were older (63.5 vs 57.6 years, P = .01), were less likely to be
      male (53.1% vs 76.5%, P = .03), and had a lower mean BMI (24.5 vs 28.4 kg/m2, P =
      .009). Eighty-five subjects had HPV-positive disease, and they had a higher BMI
      (28.2 vs 24.2 kg/m2, P = .01) than that of patients without HPV. Twenty-one
      subjects who were HPV positive had less cancer recurrence (24.7% vs 48.1%, P =
      .04) than that of their HPV-negative counterparts. Log-rank testing showed no
      difference in DFS ( P = .06) associated with sarcopenia but a significant
      difference in OS ( P = .049). There were differences in DFS ( P = .009) and OS (
      P = .023) based on HPV status. According to univariable and multivariable models,
      HPV positivity exhibited improved DFS and OS. Sarcopenia was not statistically
      significant in survival models; however, it was associated with increased
      mortality and recurrence. Conclusion Sarcopenia is a prognostic factor affecting
      OS independent of HPV status in advanced oropharyngeal cancer.

PMID- 30105923
TI  - Low levels of modern contraceptive use and associated factors in the Western
      Balkans.
AB  - OBJECTIVES: The objective of this research was to determine modern contraceptive
      use (MCU) and explore factors associated with MCU in the Western Balkans.
      METHODS: Multiple Indicator Cluster Survey (MICS) data from Bosnia and
      Herzegovina, Kosovo, Macedonia, Montenegro and Serbia, including the datasets
      from Roma settlements, were merged. Bivariate and multivariate analyses were used
      to assess which factors were associated with MCU among married women aged 15-49
      in the region. RESULTS: Among the 11,381 women surveyed, 13.75% reported MCU and
      23.74% justified domestic violence. While bivariate analysis indicated that women
      who expressed justification of domestic violence were less likely to report MUC,
      this was not the case after adjusting for sociodemographic factors. Multivariate
      analysis showed that Roma were less likely than non-Roma to engage in MCU.
      Additionally, increased education, increased wealth, and urban residency were
      significantly associated with increased likelihood of MCU. CONCLUSION: The
      results highlight the need for more attention from research, programming and
      policy communities in order to better understand and address the overall
      problematically low level of MCU and factors associated with low MCU. More
      efforts are needed to address the disparities in MCU among Roma women and women
      of lower socioeconomic status.

PMID- 30105924
TI  - Tanshinone IIA Activates Nuclear Factor-Erythroid 2-Related Factor 2 to Restrain
      Pulmonary Fibrosis via Regulation of Redox Homeostasis and Glutaminolysis.
AB  - AIMS: Pulmonary fibrosis (PF) is characterized by myofibroblast activation
      through oxidative stress. However, the precise regulation of myofibroblast
      transdifferentiation remains largely uncharacterized. RESULTS: In this study, we
      found that tanshinone IIA (Tan-IIA), an active component in the root of Salvia
      miltiorrhiza Bunge, can suppress reactive oxygen species (ROS)-mediated
      activation of myofibroblast and reduce extracellular matrix deposition in
      bleomycin (BLM)-challenged mice through the regulation of nuclear factor
      erythroid 2-related factor 2 (Nrf2). Additionally, Tan-IIA restored redox
      homeostasis by upregulating Nrf2 with NADPH oxidase 4 suppression and effectively
      prevented myofibroblast activation by blocking ROS-mediated protein kinase C
      delta (PKCdelta)/Smad3 signaling. Nrf2 knockdown in the fibroblasts and the lungs
      of BLM-treated mice reduced the inhibitory effects of Tan-IIA, indicating the
      essential role of Nrf2 in the Tan-IIA activity. Tan-IIA impaired the binding of
      kelch-like ECH-associated protein 1 (Keap1) to Nrf2 by promoting the degradation
      of Keap1 and thereby increasing Nrf2 induction by protecting Nrf2 stability
      against ubiquitination and proteasomal degradation. Importantly, we also found
      that the glutamate anaplerotic pathway was involved in energy generation and
      biosynthesis in activated myofibroblasts and their proliferation. Tan-IIA shunted
      glutaminolysis into glutathione (GSH) production by activating Nrf2, resulting in
      the reduction of glutamate availability for tricarboxylic acid cycle. Ultimately,
      myofibroblast activation was prevented by impairing cell proliferation.
      Innovation and Conclusion: In addition to the regulation of redox homeostasis,
      our work showed that Tan-IIA activated Nrf2/GSH signaling pathway to limit
      glutaminolysis in myofibroblast proliferation, which provided further insight
      into the critical function of Nrf2 in PF. Antioxid. Redox Signal. 00, 000-000.

PMID- 30105925
TI  - Rucaparib in ovarian cancer: extending the use of PARP inhibitors in the
      recurrent disease.
AB  - Rucaparib is a potent inhibitor of poly (ADP-ribose) polymerase (PARP) PARP1,
      PARP2 and PARP3, and to a lesser extent, PARP4, PARP10, PARP12, PARP15 and
      PARP16. Study 10 and ARIEL2 evaluated the use of rucaparib as treatment in
      patients with recurrent high-grade ovarian carcinoma and resulting in approval of
      rucaparib for patients with both germline and somatic BRCA mutation. Data from
      the Phase III trial ARIEL3 led to approval in platinum-sensitive disease as
      maintenance. This article reviews the efficacy, safety, pharmacokinetics and
      pharmacodynamics of rucaparib as well as future and ongoing trials.

PMID- 30105926
TI  - [EXPRESS] Heterosynaptic LTP from the anterior cingulate cortex to the spinal
      cord in adult rats.
AB  - Spinal nociceptive transmission receives biphasic modulation from supraspinal
      structures. Recent studies demonstrate that the anterior cingulate cortex (ACC)
      facilitates spinal excitatory synaptic transmission and nociceptive reflex.
      However, whether the top-down descending facilitation can cause long-term
      synaptic changes in spinal cord remains unclear. In the present study, we
      recorded C-fiber evoked field potentials in spinal dorsal horn and found that the
      ACC stimulation caused enhancement of C fiber mediated responses. The enhancement
      lasted for more than a few hours. Spinal application of NMDA receptor antagonist
      D-AP5 abolished this enhancement, suggesting the activation of NMDA receptor is
      required. Furthermore, spinal application of methysergide, a serotonin receptor
      antagonist, also blocked the ACC induced spinal long-term potentiation (LTP). Our
      results suggest that the ACC stimulation can produce heterosynaptic form of LTP
      at the spinal cord dorsal horn, and this novel form of LTP may contribute to top
      down long-term facilitation in chronic pain conditions.

PMID- 30105927
TI  - Computational prediction of antifungal peptides via Chou's PseAAC and SVM.
AB  - With the increase in immunocompromised patients in the recent years, fungal
      infections have emerged as new and serious threat in hospitals. This, and the
      insufficiency of current antifungal therapies alongside their toxic effects on
      patients, has led to the increased interest in seeking new antifungal peptides.
      In the present study, we have developed a prediction method for screening of
      antifungal peptides. For this, we have chosen Chou's pseudo amino acid
      composition (PseAAC) to translate peptide sequences into numeric values. Thus,
      the SVM classifier was performed for binomial classification of antifungal
      peptides. The performance of the classifier was evaluated via ten-fold cross
      validation and an independent dataset. For further validation of the model
      developed, 22 P24-derived peptides were predicted using the classifier and in
      vitro assays were performed on the three peptides with the highest prediction
      score. The results showed that the PseAAC [Formula: see text] SVM method is able
      to predict AFPs with ACC of 94.76%. In vitro results also validate the SEN and
      SPC of the classifier. The results suggest that the computational approach used
      in this study is highly efficient for prediction of antifungal peptides, which
      can save time and money in AFP screening and synthesis of novel peptides.

PMID- 30105928
TI  - A hybrid solver for protein multiple sequence alignment problem.
AB  - In this work, a novel hybrid model called PSOSA for solving multiple sequence
      alignment (MSA) problem is proposed. The developed approach is a combination
      between particle swarm optimization (PSO) algorithm and simulated annealing (SA)
      technique. In our PSOSA approach, PSO is exploited in global search, but it is
      easily trapped into local optimum and may lead to premature convergence. SA is
      incorporated as local improvement approach to overcome local optimum problem and
      intensify the search in local regions to improve solution quality. Numerical
      results on BAliBASE benchmark have shown the effectiveness of the proposed method
      and its ability to achieve good quality solutions when compared with those given
      by other existing methods.

PMID- 30105930
TI  - Potential Cytochrome P450 Drug-Drug Interactions among Pediatric Patients
      Undergoing Tonsillectomy.
AB  - Objective To evaluate the frequency of potential cytochrome P450 (CYP) drug-drug
      interactions affecting opioid metabolism among children undergoing
      adenotonsillectomy. Study Design Case series with chart review. Setting Tertiary
      care children's hospital. Subjects and Methods A retrospective review was
      conducted of 1000 patients undergoing adenotonsillectomy at Children's Hospital
      of Wisconsin. The discharge medication reconciliation form was reviewed. Each
      patient's list of medications was compared with various published sources to
      determine whether medications causing CYP inhibition or induction were present.
      Results There were 157 unique medications with systemic absorption given
      postoperatively to this patient cohort. Eight percent of patients were on at
      least 5 medications after surgery other than their posttonsillectomy medication.
      The 5 most commonly prescribed medications were albuterol, cetirizine,
      fluticasone nasal spray, montelukast, and polyethylene glycol. Per a list of
      known CYP inducers and inhibitors published by the US Food and Drug
      Administration, 30 (3%) patients were on a medication that inhibited CYP3A4; 1
      patient was on a CYP3A4 inducer, prednisone; and 46 (5%) patients were on a
      medication that inhibited CYP2D6. Conclusions A small fraction of patients
      undergoing adenotonsillectomy are on medications that potentially alter the
      metabolism of opioid pain medications. Given the narrow therapeutic index of
      opioids and increased sensitivity to opioids among patients with obstructive
      sleep apnea, drug-drug interactions need to be considered as they relate to
      whether an opioid is appropriate and at what dose.

PMID- 30105929
TI  - Poor codon optimality as a signal to degrade transcripts with frameshifts.
AB  - Frameshifting errors are common and mRNA quality control pathways, such as
      nonsense-mediated decay (NMD), exist to degrade these aberrant transcripts.
      Recent work has shown the existence of a genetic link between NMD and codon-usage
      mediated mRNA decay. Here we present computational evidence that these pathways
      are synergic for removing frameshifts.

PMID- 30105931
TI  - Radioiodine Refractory Differentiated Thyroid Cancer: Time to Update the
      Classifications.
AB  - BACKGROUND: The management of aggressive and progressing metastatic
      differentiated thyroid cancer (DTC) is very difficult, and the determination as
      to when such patients are refractory to 131I therapy (e.g., radioiodine
      refractory) is problematic and controversial. OBJECTIVE: The objective of this
      review is to discuss (i) the present major classifications of radioiodine
      refractory disease in DTC, (ii) factors that should be considered before
      designating a patient's DTC as radioiodine refractory, (iii) potential approaches
      and caveats to help manage and minimize a patient's exclusion from an 131I
      therapy that may have potential benefit in patients with aggressive and
      progressing metastatic DTC, (iv) next steps for revision of the classifications
      of radioiodine refractory DTC, and (v) areas for future research. SUMMARY: To
      date, the classifications of radioiodine refractory DTC, although very useful,
      are not sacrosanct especially in the context of individualized patient
      management, and merely because a patient meets one or more of the various
      classifications, one should not consider by definition, fiat, or de facto that
      that a patient's DTC is radioiodine refractory. Rather, each patient should be
      individually managed with a good understanding of the limitations of the various
      classifications and potential approaches to help manage that patient. With
      awareness of the suggestions and caveats discussed herein and with assessment of
      the many other factors that affect the patient's specific clinical situation, the
      managing physician can deliver appropriate individualized patient care. A multi
      organizational committee should be established as a standing committee to
      supervise and assist in the update of the classifications of radioiodine
      refractory DTC, including discussions of their limitations. CONCLUSION:
      Classifications to help determine radioiodine refractory disease will continue to
      evolve as (i) more studies are published, (ii) managing physicians better
      understand the limitations and confounding factors of present classifications,
      and (iii) new agents either increase or reestablish 131I uptake.

PMID- 30105932
TI  - A Case Series of Parechovirus Encephalopathy: Apnea and Autonomic Dysregulation
      in Critically Ill Infants.
AB  - This article aims to describe a rare cause of severe encephalitis in 2 cases of
      infants with signs of intracranial hypertension and severe autonomic
      dysregulation. The authors conclude that human parechoviruses are becoming a more
      recognized cause of encephalitis because of the increasing use of rapid detection
      methods. With early recognition of this clinical entity, improved care can be
      administered.

PMID- 30105935
TI  - Removal of Acid Blue 62 textile dye from aqueous solutions by cerium reagents.
AB  - The removal of Acid Blue 62 (AB62) dye which is known as a pollutant agent and
      contains in wastewater of textile industry has been studied in this work by using
      five various cerium compounds as the oxidizing agents. The parameters involved in
      the oxidation reaction such as pH, initial dye concentration and the oxidizing
      agent dosage have been investigated using both batch and semi-batch reactors at
      ambient temperature. The results indicated that the rate of oxidation for various
      cerium reagents is in the following order: CeF4 > (NH4)2Ce (NO3)6 > Ce (SO4)2 >
      CeCl3 > Ce (CH3COO)3, where cerium fluoride (CeF4) had the highest removal
      yields, 99.9% and 95%, for dye de-colouration and COD (chemical oxygen demand),
      respectively. The analysis of the dye removal was done by using UV-VIS
      spectrometry, GC-MS and HPLC methods which indicated the aromatic ring cleavage
      of AB62 dye by CeF4. The half-life measurement was employed to evaluate the
      reaction rate model for decomposition of AB62 dye by CeF4.

PMID- 30105934
TI  - Building capacity in neurodevelopment assessment of children in sub-Saharan
      Africa: A quality assurance model to implement standardized neurodevelopment
      testing.
AB  - Compromised neurodevelopment (ND) among infants and children is prevalent in sub
      Saharan Africa. Standardized testing of ND is frequently prohibitive in these
      contexts, as tests require skilled staff for their application. In this paper, we
      present a quality assurance (QA) model (QualiND) for standardized ND testing,
      discussing findings and implications from our experience applying the Kaufman
      Assessment Battery for Children second edition (KABC-II). The QualiND model was
      implemented within IMPAACT P1104s study, a multisite, prospective study including
      615 children affected by HIV. From 2014 to 2016, the QualiND managed 18 testers
      across 6 sites located in 4 African countries applying the KABC-II in 9 local
      languages. The QualiND is a multilevel, video-assisted iterative model
      incorporating remote evaluation, feedback, and supervision roles. Using an ad hoc
      rubric, videos of test application were evaluated by experienced staff in a
      centralized QA center. At each study site, testers and supervisors reviewed
      feedback from videos received via email from the QA center and devised an action
      plan to address testing errors and deficiencies. There were few instances of
      invalid tests and few barriers to test completion. Over 97% of KABC-II tests
      across sites were considered to be valid by the QA center. Overall, the QualiND
      model was a useful platform for remote supervision to nonspecialist and minimally
      trained research staff. The QualiND model may be useful to researchers and
      organizations involved in measuring early child development using standardized
      tests in low and middle-income countries.

PMID- 30105933
TI  - The etiological changes of acetylation in peripheral nerve injury-induced
      neuropathic hypersensitivity.
AB  - Neuropathic pain is a common chronic pain condition with mechanisms far clearly
      been elucidated. Mounting preclinical and clinical studies have shown neuropathic
      pain is highly associated with histone acetylation modification, which follows
      expression regulation of various pain-related molecules such as mGluR1/5,
      glutamate aspartate transporter, glutamate transporter-1, GAD65, Nav1.8, Kv4.3,
      MU-opioid receptor, brain-derived neurotrophic factor, and certain chemokines. As
      two types of pivotal enzymes involved in histone acetylation, histone
      deacetylases induce histone deacetylation to silence gene expression; in
      contrast, histone acetyl transferases facilitate histone acetylation to
      potentiate gene transcription. Accordingly, upregulation or blockade of
      acetylation may be a promising intervention direction for neuropathic pain
      treatment. In fact, numerous animal studies have suggested various histone
      deacetylase inhibitors, Sirt (class III histone deacetylases) activators, and
      histone acetyl transferases inhibitors are effective in neuropathic pain
      treatment via targeting specific epigenetic sites. In this review, we summarize
      the characteristics of the molecules and mechanisms of neuropathy-related
      acetylation, as well as the acetylation upregulation and blockade for neuropathic
      pain therapy. Finally, we will discuss the current drug advances focusing on
      neuropathy-related acetylation along with the underlying treatment mechanisms.

PMID- 30105936
TI  - Subcutaneous belimumab in the treatment of systemic lupus erythematosus.
AB  - Systemic lupus erythematosus is a chronic autoimmune disease with various
      clinical manifestations, organ involvement and laboratory findings. The disease
      can involve any organ including skin, joints, kidneys, central and peripheral
      nervous system, cardiovascular system and more. Currently, the cornerstone of
      treatment includes antimalarial and immunosuppressive medications and
      glucocorticosteroids. Recently, great effort has been invested in finding more
      targeted drugs for achieving better control of the disease with less adverse
      events. Intravenous belimumab was the first and only biologic drug to be approved
      by the US FDA and Health Canada for lupus over the last 50 years, and recently
      was studied in subcutaneous form. This paper will review the major belimumab
      trials with a focus on the subcutaneous form.

PMID- 30105937
TI  - Peripheral vascular manifestation in patients receiving an amphetamine analog: A
      case series.
AB  - Amphetamine and its related derivatives and analogues (ADRA) are highly addictive
      central nervous system stimulants that are used commonly in the treatment of
      attention-deficit/hyperactivity disorder and narcolepsy. These medications are
      associated with many side effects but reports of peripheral arterial
      manifestations associated with ADRA usage are scarce. We retrospectively reviewed
      the records of 16 patients (median age 37 years (IQR 31-47), 13 females) referred
      to a single tertiary referral service while receiving ADRA. Follow-up was
      available for a median of 3 years (IQR 3-4.5). The most common presentation
      (62.5%) was mild vasospastic symptoms involving the upper, lower or both
      extremities. Six patients developed severe manifestations including tissue loss
      and the need for lower extremity amputation. Most patients (75%) refused to stop
      the medication during follow-up. Underlying rheumatologic disorders were found in
      25% of the patients, and the presence of rheumatologic disease seemed to be
      associated with more severe vascular manifestations. In conclusion, it is
      important to search for ADRA usage as part of the differential diagnosis of
      digital ischemia.

PMID- 30105938
TI  - Temporal trends in the management and clinical outcomes of lower extremity
      arterial thromboembolism within a national Veteran population.
AB  - Lower extremity arterial thromboembolism is associated with significant morbidity
      and mortality. We sought to establish temporal trends in the incidence,
      management and outcomes of lower extremity arterial thromboembolism within the
      Veterans Affairs Healthcare System (VAHS). We identified patients admitted to
      VAHS between 2003 and 2014 with a primary diagnosis of lower extremity arterial
      thromboembolism. Medical and procedural management were ascertained from
      pharmaceutical and administrative data. Subsequent rates of major adverse limb
      events (MALE), major adverse cardiovascular events (MACE), and mortality were
      calculated using Cox proportional hazards models. From 2003 to 2014, there were
      10,636 patients hospitalized for lower extremity thromboembolism across 140
      facilities, of which 8474 patients had adequate comorbid information for
      analysis. Age-adjusted incidence decreased from 7.98 per 100,000 patients (95%
      CI: 7.28-8.75) in 2003 to 3.54 (95% CI: 3.14-3.99) in 2014. On average, the
      likelihood of receiving anti-platelet or anti-thrombotic therapy increased 2.3%
      (95% CI: 1.2-3.4%) per year during this time period and the likelihood of
      undergoing endovascular revascularization increased 4.0% (95% CI: 2.7-5.4%) per
      year. Clinical outcomes remained constant over time, with similar rates of MALE,
      MACE and mortality at 1 year after adjustment. In conclusion, the incidence of
      lower extremity arterial thromboembolism is decreasing, with increasing
      utilization of anti-thrombotic therapies and endovascular revascularization among
      those with this condition. Despite this evolution in management, patients with
      lower extremity thromboembolism continue to experience high rates of amputation
      and death within a year of the index event.

PMID- 30105940
TI  - Comparative analysis of jaw morphology and temporomandibular disorders: A three
      dimension imaging study.
AB  - OBJECTIVE: To investigate the association between volumetric measurements of
      craniofacial morphology and temporomandibular disorders (TMDs). METHODS:
      Computerized tomography (CT) scans of 20 individuals aged 18 to 40 with (TMD
      group) or without TMJ pain (control group) were gathered based on a case-control
      design. Three-dimensional reconstructions were performed to evaluate the gonial
      angle, condylar volume, and the distance between the posterior edge of the
      condyle and the sigmoid notch. RESULTS: The gonial angle was significantly larger
      (8% difference) in the TMD group with respect to controls, whereas the condylar
      volume was significantly higher in the control group (15.2% difference). No
      significant difference was found in the linear distance. CONCLUSION: There is an
      association between the presence of TMJ pain and some features of craniofacial
      morphology. Individuals with TMJ pain have a lower condylar volume and a tendency
      towards hyperdivergent growth.

PMID- 30105939
TI  - Heterogeneous effects of cholecystokinin on neuronal response properties in deep
      layers of rat barrel cortex.
AB  - Cholecystokinin (CCK) is one of the most studied neuropeptides in the brain. In
      this study, we investigated the effects of CCK-8s and LY225910 (CCK2 receptor
      antagonist) on properties of neuronal response to natural stimuli (whisker
      deflection) in deep layers of rat barrel cortex. This study was done on 20 male
      Wistar rats, weighing 230-260 g. CCK-8s (300 nmol/rat) and LY225910 (1 umol/rat)
      were administered intracerebroventricularly (ICV). Neuronal responses to
      deflection of principal (PW) and adjacent (AW) whiskers were recorded in the
      barrel cortex using tungsten microelectrodes. Computer controlled mechanical
      displacement was used to deflect whiskers individually or in combination at 30 ms
      inter-stimulus intervals. ON and OFF responses for PW and AW deflections were
      measured. A condition-test ratio (CTR) was computed to quantify neuronal
      responses to whisker interaction. ICV administration of CCK-8s and LY225910 had
      heterogeneous effects on neuronal spontaneous activity, ON and OFF responses to
      PW and/or AW deflections, and CTR for both ON and OFF responses. The results of
      this study demonstrated that CCK-8s can modulate neuronal response properties in
      deep layers of rat barrel cortex probably via CCK2 receptors.

PMID- 30105941
TI  - AbobotulinumtoxinA for the treatment of overactive bladder.
AB  - INTRODUCTION: Overactive bladder is a common condition that can have a negative
      impact on quality of life. Botulinum Toxin A is a third line treatment for
      overactive bladder following conservative measures and anticholinergic
      medication. At present, OnabotulinumtoxinA is the only preparation licensed for
      this indication. More recently, trials have been undertaken to compare the
      efficacy of this to AbobotulinumtoxinA. Areas covered: This article aims to
      provide an overview of AbobotulinumtoxinA, which is currently not yet licensed
      for overactive bladder or neurogenic detrusor overactivity. It will detail the
      pharmacokinetics and dynamics, assess the available clinical trial data and make
      comparisons with current clinical practice. A systematic literature search was
      completed, using ovid Medline and Embase, with the aim to review all data
      concerning the administration of AbobotulinumtoxinA for the treatment of
      overactive bladder. Expert opinion: Currently, there are a lack of data on the
      use of AbobotulinumtoxinA for overactive bladder or neurogenic detrusor
      overactivity. Current evidence concentrates on its use in neurogenic detrusor
      overactivity, and there are data to show it may be as efficacious as
      OnabotulinumtoxinA. However, there is a lack of homogenous data to compare the
      two products and therefore we are unable to recommend this currently.

PMID- 30105942
TI  - The effect of cement mantle thickness on strain energy density distribution and
      prediction of bone density changes around cemented acetabular component.
AB  - Cement mantle thickness is known to be one of the important parameters to reduce
      the failure of the cemented acetabular component. The thickness of the cement
      mantle is also often influenced by the positioning of the acetabular cup. The aim
      of this study is to determine the effect of uniform and non-uniform cement mantle
      thickness on strain energy density distribution and prediction of the possibility
      of bone remodelling around the acetabular region. Furthermore, tensile stress
      distribution in the cement mantle due to non-uniform cement mantle thickness was
      also investigated. Three-dimensional finite element models of intact and 17
      implanted pelvic bone were developed based on computed tomography data sets.
      Results indicate that implantation with non-uniform cement thickness variation in
      the anterior-posterior direction has a significant influence on strain energy
      density distribution around the acetabulum as compared to thickness variation in
      the superior-inferior direction. Increase in density is predicted at the anterior
      part of the acetabulum, whereas density decrease is predicted at the posterior,
      inferior and superior part of the acetabulum. The non-uniform cement mantle
      thickness affected the tensile stress distribution in the cement mantle, in
      particularly superiorly placed acetabular cup. This study concludes that uniform
      cement thickness is desired for the longer success of the cemented acetabular
      component.

PMID- 30105943
TI  - BPI-ANCA in chronic obstructive pulmonary disease with pulmonary Pseudomonas
      aeruginosa colonisation: a novel indicator of poor prognosis.

PMID- 30105944
TI  - Funnel-Guided Positioning of Multicellular Microtissues to Build Macrotissues.
AB  - The field of tissue engineering is developing new additive manufacturing
      technologies to fabricate 3D living constructs for use as in vitro platforms for
      the testing of drugs and chemicals, or to restore lost function in vivo. In this
      article, we describe the funnel-guide (FG), a new additive manufacturing strategy
      for the noncontact manipulation and positioning of multicellular microtissues and
      we show that the FG can be used to build macrotissues layer by layer. We used
      agarose micromolds to self-assemble cells into toroid-shaped and honeycomb-shaped
      microtissues, and observed that when falling in cell culture medium, the
      microtissues spontaneously righted themselves to a horizontal orientation. We
      fabricated a funnel to guide these falling toroids and honeycombs into precise
      positions and stack them, wherein they fused to form tubular structures. We
      tested multiple cell types and toroid sizes, and ultimately used the FG to create
      a stack of 45 toroids that fused into a tube 5 mm long with an inner diameter of
      600 MUm. The FG is a new principle for the manipulation of microtissues and is a
      platform for the layer-by-layer positioning of microtissue building blocks to
      form macrotissues.

PMID- 30105945
TI  - Nasal cannula technique for ventilating during the administration of general
      anesthesia in neonates and pediatric patients.
AB  - OBJECTIVE: Minor surgeries on the oral cavity, e.g., frenulectomies, are often
      performed under general mask anesthesia. The objective is to present the nasal
      cannula technique for ventilating step-by-step method for ventilating during
      general anesthesia for minor surgeries in neonates and pediatric patients.
      TECHNIQUE: The nasal cannula technique for ventilating has been used in over 20
      pediatric cases (neonates and toddlers), without the need to re-mask during the
      procedure and without complications or oxygen desaturations. After induction of
      general mask anesthesia, propofol with or without adjunctive ketamine is
      administered. The anesthesia mask is exchanged with a nasal cannula, using the
      largest sized prongs that accommodate the nares, and the nasal cannula is
      connected to the anesthesia circuit. This permits administration of inspired
      fractions of oxygen. CONCLUSION: The nasal cannula technique for ventilating
      provides a safe method for delivering general anesthesia and ventilating during
      minor surgeries for neonates and pediatric patients.

PMID- 30105946
TI  - App-based learning as an alternative for instructors in teaching basic life
      support to school children: a randomized control trial.
AB  - BACKGROUND: The importance of early cardiopulmonary resuscitation (CPR) during an
      out-of-hospital cardiac arrest (OHCA) cannot be emphasized enough and has a major
      impact on survival. Unfortunately, CPR education in schools is often inadequate
      or non-existing due to lack of educators and financial resources. The
      introduction of application-based teaching could facilitate education as no
      instructor is needed. The aim of present study is to compare app-based self
      teaching (intervention group) with a traditional instructor-led course (control
      group). This trial is in line with the endorsement of training school children by
      the World Health Organization (WHO). METHODS: This randomized controlled trial
      contains 165 participants between 16 and 18 years. The control group followed an
      instructor-led course, while the intervention group used a tablet application to
      complete a self-education course.Both groups were taught in separated classes
      during 40 min and used manikins and automated external defibrillator (AED)
      trainer kits. Before and after training, both groups were evaluated in a
      practical test to examine their skills (an overall score and sub-scores on
      different sections were obtained, following ERC 2015 guidelines). RESULTS: No
      significant difference (p = 0.304) in overall teaching effectiveness was found
      between both groups. Although, in a sub-analysis, we found significantly better
      results for the instructor group for checking airway (p = 0.018), asking for an
      AED (p < 0.01) and shocking the patient (p = 0.002). CONCLUSIONS: App-based
      teaching can be a valuable alternative for classic instructor-based education.
      Yet new apps have to be evaluated before being implemented in CPR education.

PMID- 30105947
TI  - Intensity-Modulated Radiation Therapy With or Without Concurrent Chemotherapy in
      Nonanaplastic Thyroid Cancer with Unresectable or Gross Residual Disease.
AB  - BACKGROUND: Differentiated thyroid cancer typically has an indolent clinical
      course but can cause significant morbidity by local progression. Oncologic
      surgical resection can be technically difficult due to the proximity to critical
      normal structures in the neck. Our objective was to review the safety,
      feasibility, and outcomes of definitive-intent intensity-modulated radiation
      therapy (IMRT) and to analyze whether patients receiving concurrent chemotherapy
      (CC-IMRT) had higher rates of disease control and survival over IMRT alone in
      patients with unresectable or gross residual disease (GRD). METHODS: Eighty-eight
      patients with GRD or unresectable nonanaplastic, nonmedullary thyroid cancer
      treated with definitive-intent IMRT between 2000 and 2015 were identified. Local
      progression-free survival (LPFS), distant metastasis-free survival (DMFS), and
      overall survival (OS) were evaluated using the Kaplan-Meier method. Univariate
      and multivariate analyses using cox regression were used to determine the impact
      of clinical conditions and treatment on LPFS, DMFS, and OS. RESULTS: Of the 88
      patients identified, 45 (51.1%) were treated CC-IMRT and 43 (48.9%) were treated
      with IMRT alone. All patients treated with CC-IMRT received weekly doxorubicin
      (10 mg/m2). The median follow-up among surviving patients was 40.3 months and
      29.2 months for all patients. The LPFS at 4 years was 77.3%. Patients receiving
      CC-IMRT had higher LPFS compared with IMRT alone (CC-IMRT 85.8% vs. IMRT 68.8%, p
      = 0.036). The 4-year OS was 56.3% for all patients. Patients treated with CC-IMRT
      had higher OS compared to patients treated with IMRT alone (CC-IMRT 68.0% vs.
      IMRT 47.0%, p = 0.043). On multivariate analysis, receipt of concurrent
      chemotherapy was associated with a lower risk of death (HR 0.395, p = 0.019) and
      lower risk of local failure (HR 0.306, p = 0.042). Grade 3+ acute toxicities
      occurred in 23.9% of patients, the most frequent being dermatitis (18.2%) and
      mucositis (9.1%). 17.1% of patients required a percutaneous endoscopic
      gastrostomy (PEG) tube during or shortly after completion of RT, with 10.1% of
      patients needing a PEG more than 12 months after therapy. The rates of acute and
      late toxicities were not statistically higher in the CC-IMRT cohort, although
      trends towards higher toxicity in the CC-IMRT were present for dermatitis and PEG
      requirement. CONCLUSIONS: IMRT is a safe and effective means to achieve local
      control in patients with unresectable or incompletely resected nonanaplastic,
      nonmedullary thyroid cancer. Concurrent doxorubicin was not associated with worse
      toxicity and should be considered in these patients given its potential to
      improve local control and overall survival.

PMID- 30105948
TI  - Intermediate-Risk Papillary Thyroid Cancer: Risk Factors for Early Recurrence in
      Patients with Excellent Response to Initial Therapy.
AB  - BACKGROUND: Patients with excellent response to initial therapy have a low rate
      of tumor recurrence. The objectives of this study were to evaluate the rate of
      early tumor recurrence in patients with intermediate-risk papillary thyroid
      cancer who had an excellent response to initial treatment and to identify risk
      factors. METHODS: This retrospective cohort study included 217 patients with
      American Thyroid Association intermediate-risk papillary thyroid cancer who had a
      documented excellent response to initial treatment (total thyroidectomy and
      adjuvant therapy with 100-150 mCi [3.7-5.5 GBq] of radioactive iodine [RAI]). The
      assessed outcome was recurrence, defined as new evidence of disease after any
      disease-free period. Multivariate logistic regression and Cox regression models
      were used to determine the factors associated with recurrence upon recording
      clinical, surgical, and pathology variables. RESULTS: Sixteen (7.4%) cases of
      recurrent disease were documented after a median follow-up period of 42 months
      (range 17-88 months). Structural recurrence was documented in 10 (62.5%)
      patients, and biochemical recurrence was documented in the remaining six
      patients. The logistic regression model identified a significant association
      between early recurrence and pN1b involvement (odds ratio [OR] = 10.81
      [confidence interval (CI) 1.87-62.59]), lateral neck RAI uptake (OR = 6.06 [CI
      1.67-22]), and pre-ablation thyroglobulin >10 ng/mL (OR = 4.01 [CI 1.16-13.85]).
      Variables that proved significant in the Cox regression model were: pN1b
      involvement (hazard ratio = 9.6 [CI 1.91-48.52]) and lateral neck RAI uptake
      (hazard ratio = 5.95 [CI 1.86-18.97]). CONCLUSION: The observed early recurrence
      rate of 7.4% is uncharacteristically high for a population of patients who had an
      excellent response to initial treatment. The significant association that was
      found between recurrent disease and lateral neck lymph node metastasis, lateral
      neck I131 uptake in post-therapy whole-body scan, and pre-ablation thyroglobulin
      levels >10 ng/mL indicates that early recurrence (<5 years) most likely indicates
      progression of micrometastatic disease already present at diagnosis and
      unsuccessfully eradicated with initial therapy.

PMID- 30105949
TI  - Sonographically Estimated Risks of Malignancy for Thyroid Nodules Computed with
      Five Standard Classification Systems: Changes over Time and Their Relation to
      Malignancy.
AB  - BACKGROUND: Over 50% of newly diagnosed thyroid nodules are either cytologically
      benign or presumed to be benign on the basis of low-suspicion sonographic
      findings. The strategies used for their long-term surveillance are based mainly
      on the estimated residual risk of malignancy calculated with various
      ultrasonographic classification systems (e.g., Thyroid Image Reporting and Data
      Systems [TIRADS]). We conducted a longitudinal study to evaluate the temporal
      stability of the initial risk estimates computed with five widely used systems
      and to determine whether risk class increases during follow-up are indeed
      predictive of malignancy. METHODS: We re-analyzed data prospectively collected at
      a single academic referral center on 232 patients (age: 54.1 +/- 13.7 years) with
      432 asymptomatic, sonographically or cytologically benign thyroid nodules at
      baseline (T0) and 122 new nodules that were present five years later (T5). At
      both time points, the sonographically estimated risk of malignancy was calculated
      as recommended by the American Association of Clinical Endocrinologists/American
      College of Endocrinology/Associazione Medici Endocrinologi, the American College
      of Radiologists' TIRADS, the American Thyroid Association's 2015 practice
      guidelines, the European Thyroid Association's TIRADS (EU-TIRADS), and the TIRADS
      of the Korean Society of Thyroid Radiology (K-TIRADS). RESULTS: For 57 to 127
      (13.2-29.4%) of the original nodules, depending on the system used, the estimated
      malignancy risk increased over the 5-year interval. Of the nodules whose baseline
      risk had not warranted cytological assessment, very few (6.3-8.3%) met the
      criteria for cytology at the 5-year evaluation. Biopsy was indicated for only 4
      to 8 (3.3-6.6%) of the new nodules based on T5 risk estimates. Despite these
      changes, none of the 232 patients was ever diagnosed with a cancer. CONCLUSIONS:
      Ultrasound-based risk classes of presumably benign thyroid nodules remain fairly
      stable over time, and changes warranting biopsy are rare indeed. The appearance
      of new nodules is a frequent event, but very few (<5%) are classified as high
      risk, and only the 3-7% meet the criteria for cytological assessment.
      Collectively, these findings support the view that patients with presumably
      benign thyroid nodules can be safely followed with less intensive protocols.

PMID- 30105950
TI  - Impact of cultural background on fundamental movement skill and its correlates.
AB  - Children's fundamental movement skill levels (FMS) predict moderate-to-vigorous
      physical activity (MVPA). Asian children have been reported as less active than
      English-Europeans, possibly due to poorer skills. This study compared the FMS of
      children from Culturally and Linguistically Diverse (CALD) backgrounds and
      examined FMS correlates. A total of 261 children (122 males) aged 9-to-11 years
      were divided based on language spoken at home: English-European (n = 105) and
      Asian (n = 156). Height, mass, FMS (Test of Gross Motor Development-2), MVPA
      (accelerometer) and cardio-respiratory fitness (20m multistage shuttle run) were
      directly measured. Sex, age, language and perceived sport competence (CY-PSPP)
      were self-reported. Independent sample t-tests assessed age, BMI, FMS and
      perception by CALD group. Linear mixed models examined FMS correlates. Asian
      speaking children had lower object control skill (35.5 v 37.2; CI [0.17, 3.18]; p
      < 0.03) compared to English-European- children, but no between-group differences
      in locomotor skills were observed. Fitness, physical activity and sport
      competence perception were positively associated with object control, yet
      adjusting for these variables (and age and BMI) did not remove the CALD effect (B
      = -2.02, SE = 0.69, p = 0.004). Cultural factors may affect object control
      competence in Asian-Australian children.

PMID- 30105951
TI  - Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and
      Poorly Differentiated Thyroid Cancer.
AB  - BACKGROUND: Dysregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is
      frequent in advanced follicular (FTC) and poorly differentiated thyroid (PDTC)
      carcinomas and has been implicated in oncogenesis and tumor progression. This
      study investigated the efficacy and safety of buparlisib, a pan-PI3K inhibitor in
      radioiodine refractory FTC and PDTC. METHODS: The primary endpoint of this open
      label, multicenter, phase 2 pilot study was progression-free survival (PFS) at 6
      months. The sample size was determined considering that a PFS <=50% at 6 months
      would denote an absence of benefits (null hypothesis). Secondary endpoints were
      objective response rate, PFS at 12 months, overall survival at 6 and 12 months,
      and safety based on the frequency and severity of adverse events (AEs). RESULTS:
      Forty-three patients (19M/24 F; median age: 67 years) with metastatic,
      radioiodine refractory, progressive disease received buparlisib, 100 mg, daily.
      Histology was PDTC in 25 (58%), FTC in 17 (40%), and Hurthle cell carcinoma in 1
      (2%). RAS mutation was found in 44% (12/27) and activation of the PI3K pathway in
      35% (8/23) of tested tumors. The probability of PFS was 41.7% [95% confidence
      interval (CI) 7.7-55.5] at 6 months and 20.9% [CI 0-35.7] at 12 months, lower
      than the 50% expected PFS. At 6 months, 25.6% patients had stable disease, 48.8%
      were progressive and 25.6% had stopped treatment due to AE. The response to
      therapy was not influenced by age, sex, histology, or genetic alterations. The
      overall survivals at 6 and 12 months were 85.9% [CI 76-97] and 78.7 % [CI 67-92],
      respectively. The mean tumor growth rate decreased from 3.78 mm/month [CI 2.61
      4.95] before treatment to 0.8 mm/month [CI -0.2-1.88] during treatment (p <
      0.02). Severe grade 3-4 AEs occurred in 27 patients (63%), including hepatitis
      (25%), hyperglycemia (21%), mood disorders (12%), and skin toxicity (12%), with
      favorable outcome after temporary or permanent treatment discontinuation or dose
      reduction. CONCLUSIONS: Buparlisib did not result in significant efficacy in
      advanced FTC and PDTC. However, the decrease in tumor growth rate may suggest
      incomplete inhibition of oncogenic pathways and/or escape mechanisms. This should
      lead to evaluate combined therapy associating inhibitors of both the PI3K and
      mitogen-activated protein kinase pathways.

PMID- 30105953
TI  - Inaugurating Our Latin American EBM/SEBM Office in Campinas Brazil: Three
      Perspectives.

PMID- 30105952
TI  - Integration of "omics" techniques: Dronedarone affects cardiac remodeling in the
      infarction border zone.
AB  - Dronedarone improves microvascular flow during atrial fibrillation and reduces
      the infarct size in acute models of myocardial infarction. However, dronedarone
      might be harmful in patients with recent decompensated heart failure and
      increases mortality in patients with permanent atrial fibrillation. A
      pathophysiological explanation for these discrepant data is lacking. This study
      investigated the effects of dronedarone on gene and protein expression in the
      infarcted area and border zone in pigs subjected to anterior ischemia/reperfusion
      myocardial infarction. The ischemia/reperfusion myocardial infarction was induced
      in 16 pigs. Eight pigs were treated with dronedarone for 28 days after myocardial
      infarction, the remaining pigs served as control. Microarray-based transcriptome
      profiling and 2D-DIGE-based proteome analysis were used to assess the effects of
      dronedarone on left ventricular gene expression in healthy (LV), infarcted (MI),
      and border zone tissue. Selected targets were validated by RT-qPCR or immunoblot
      analyses, with special emphasize given to the transcriptome/proteome overlap.
      Combined "omics" analysis was performed to identify most significant disease and
      function charts affected by dronedarone and to establish an integrated network.
      The levels of 879 (BZ) or 7 (MI) transcripts and 51 (LV) or 15 (BZ) proteins were
      significantly altered by dronedarone, pointing to a substantial efficacy of
      dronedarone in the border zone. Transcriptome and proteome data indicate that
      dronedarone influences post-infarction remodeling processes and identify
      matricellular proteins as major targets of dronedarone in this setting. This
      finding is fully supported by the disease and function charts as well as by the
      integrated network established by combined "omics". Dronedarone therapy alters
      myocardial gene expression after acute myocardial infarction with pronounced
      effects in the border zone. Dronedarone promotes infarct healing via regulation
      of periostin and might contribute to the limitation of its expansion as well as
      cardiac rupture. Thus, there are no experimental hints that dronedarone per se
      has direct harmful effects after MI in ventricular tissue. Impact statement
      Dronedarone reduced the infarct size in models of acute myocardial infarction
      (MI). Here, we show that dronedarone attenuates many of the substantial changes
      in gene expression that are provoked by acute myocardial infarction (AMI) in
      pigs. Dronedarone modifies the expression of gene panels related to post
      infarction cardiac healing and remodeling processes and, most remarkably, this
      occurs predominantly in the infarction border-zone and much less so in the vital
      or infarcted myocardium. Combined "omics" identified matricellular proteins and
      ECM as major dronedarone-regulated targets and emphasizes their relevance for
      Disease Charts and Tox Function Charts associated with tissue remodeling and
      cellular movement. The results demonstrate dronedarone's capability of regulating
      cardiac repair and remodeling processes specifically in the infarction border
      zone and identify underlying mechanisms and pathways that might be employed in
      future therapeutic strategies to improve long-term cardiac tissue function and
      stability.

PMID- 30105954
TI  - Nuclear factor erythroid 2-related factor 2 activation mediates
      hyperhomocysteinemia-associated lipolysis suppression in adipocytes.
AB  - Hyperhomocysteinemia (HHcy) is associated with suppressed lipolytic response in
      adipocytes/adipose tissue, however, the underlying mechanism remains to be
      extensively studied. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master
      transcriptional factor regulating antioxidant generation, has been recently
      reported to mediate lipid metabolism. Employing both fully differentiated 3T3-L1
      adipocytes and male C57BL/6 mice, in the present study, we investigated the
      potential involvement of Nrf2 activation in HHcy-mediated lipolytic suppression.
      Our results showed that homocysteine (Hcy) treatment resulted in suppressed
      lipolysis, evidenced by increased intracellular triglyceride (TG) accumulation,
      decreased glycerol and free fatty acid (FFA) in fully differentiated 3T3-L1
      adipocytes. Interestingly, Hcy exposure was associated with Nrf2 activation in
      adipocytes. Further studies showed that Nrf2 knockdown via siRNA transfection
      ameliorated Hcy-induced glycerol release in adipocytes. On the contrary, Nrf2
      activators, epigallocatechin gallate (EGCG) and tert-butylhydroquinone (t-BHQ),
      increased intracellular TG content and decreased glycerol release in adipocytes.
      Importantly, our in vitro observations were corroborated by our in vivo findings,
      in which Hcy feeding (0.1% wt/vol) for four weeks induced Nrf2 expression in
      adipose tissue and lowered circulating FFA and glycerol levels in mice.
      Furthermore, EGCG injection (5 mg/kg/d) decreased circulating glycerol levels in
      comparison to the control group in mice. In conclusion, these results indicated
      that Nrf2 activation in response to HHcy plays an important role in mediating Hcy
      suppressed lipolysis in adipocytes.

PMID- 30105956
TI  - President's Message.

PMID- 30105955
TI  - Mulberry and dandelion water extracts prevent alcohol-induced steatosis with
      alleviating gut microbiome dysbiosis.
AB  - Chronic alcohol intake causes hepatic steatosis and changes the body composition
      and glucose metabolism. We examined whether water extracts of mulberry (WMB) and
      white flower dandelion ( Taraxacum coreanum Nakai, WTC) can prevent and/or delay
      the symptoms of chronic ethanol-induced hepatic steatosis in male Sprague Dawley
      rats, and explored the mechanisms. Ethanol degradation was examined by orally
      administering 3 g ethanol/kg bw after giving them 0.3 g/kg bw WMB or WTC. All
      rats were continuously provided about 7 g ethanol/kg bw/day for four weeks and
      were given either of 0.1% dextrin (control), WMB, WTC, or water extracts of
      Hovenia dulcis Thunb fruit (positive-control) in high-fat diets. Area under the
      curve of serum ethanol levels was lowered in descending order of control, WTC and
      positive-control, and WMB in acute ethanol challenge. WMB and WTC prevented
      alcohol intake-related decrease in bone mineral density and lean body mass
      compared to the control. After glucose challenge, serum glucose levels increased
      more in the control group than other groups in the first part and the rate of
      decrease after 40 min was similar among all groups. These changes were associated
      with decreasing serum insulin levels. WMB had the greatest efficacy for
      decreasing triglyceride and increasing glycogen deposits. WMB and WTC prevented
      the disruption of the hepatic cells and nuclei while reducing malondialdehyde
      contents in rats fed alcohol, but the prevention was not as much as the normal
      control. The ratio of Firmicutes to Bacteroidetes in the gut was much higher in
      the control than the normal-control, but WTC and WMB decreased the ratio compared
      to the control. WMB and WTC separated the gut microbiota community from the
      control. In conclusion, WMB and WTC protected against alcoholic liver steatosis
      by accelerating ethanol degradation and also improved body composition and
      glucose metabolism while alleviating the dysbiosis of gut microbiome by chronic
      alcohol intake. Impact statement Excessive alcohol consumption is associated with
      serious pathologies and is common in much of the world. Pathologies include liver
      damage, glucose intolerance, and loss of lean body mass and bone mass. These
      pathologies are mediated by changes in metabolism as well as toxic metabolic
      byproducts, and possibly by gut dysbiosis. In this study, we demonstrate that
      aqueous extracts of mulberry and dandelion protected rats against ethanol-induced
      losses in lean body and bone masses, improved glucose tolerance and partially
      normalized gut bacterial populations, with mulberry extract being generally more
      effective. This research suggests that mulberry and dandelion extracts may have
      the potential to improve some of the pathologies associated with excess alcohol
      consumption, and that further clinical research is warranted.

PMID- 30105957
TI  - And We Never Give Up.

PMID- 30105958
TI  - Culturally Congruent End-of-Life Care: A Universal Health Need.

PMID- 30105959
TI  - Culture and Birth Outcomes in Sub-Saharan Africa: A Review of Literature.
AB  - INTRODUCTION: Almost 830 women die daily in childbirth with 550 of those deaths
      occurring in sub-Saharan Africa. This region has the highest maternal mortality
      rates in the world with 546 deaths per 100,000 live births. Research must focus
      on understanding cultural beliefs and practices to improve maternal health
      outcomes. The purpose of this review is to provide evidence of relevant cultural
      beliefs and the impact on birth outcomes for women in sub-Saharan Africa. METHOD:
      Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)
      guidelines, the literature focused on 25 articles that defined, directly or
      indirectly, associations of cultural values, beliefs, and lifeways to pregnancy
      and birth from the perspective of women of childbearing age. RESULTS: Three
      relevant categories emerged from the literature: birth outcomes, maternal care
      seeking, and maternal culture care. DISCUSSION: Women's voices and an
      understanding of cultural constructs of care are required to encourage the use of
      biomedical health system along with the use of indigenous practices.

PMID- 30105960
TI  - Predicting duodenal flows and absorption of fatty acids from dietary
      characteristics in ovine and bovine species: a meta-analysis approach.
AB  - Dietary and ruminal factors modify the ruminal biohydrogenation (RBH) of
      polyunsaturated fatty acids (FA), with duodenal FA flows being quantitatively and
      qualitatively different from FA intake. Using a meta-analysis approach from a
      database on duodenal flows of FA in ruminants, this study aimed to determine
      predictive equations for duodenal and absorbed flows of saturated FA, C18:1,
      C18:2 and C18:3 isomers, odd- and branched-chain FA (OBCFA), C20:5n-3, C22:5n-3
      and C22:6n-3 and to quantify the effects of dietary and digestive factors on
      those equations. The database was divided into four subsets: forage, seed,
      vegetable oils or animal fats (oil/fat), and fish products (fish) subsets. Models
      of duodenal and absorbed FA flows were obtained through variance-covariance
      analysis. Effects of potential interfering factors (conservation mode and
      botanical families of forages, lipid source, technological processing of lipid
      supplements, diet composition and animal characteristics) were analysed. We
      obtained 83 models for duodenal FA flows as a function of FA intake for saturated
      FA (C14:0, C16:0 and C18:0), C18:1, C18:2 and C18:3 isomers and seven other
      models for OBCFA. For the seed/oil/fat subset, intakes of total C18:3, C18:2 and
      starch content increased the duodenal t11-C18:1 flow with 0.08, 0.16 and 0.005
      g/kg of dry matter intake (DMI), respectively, whereas intake level
      [(DMI*100)/BW] decreased it. The c9c12c15-C18:3 RBH was higher for oil/fat than
      seed (96.7% v. 94.8%) and a protective effect of Leguminosae v. Gramineae against
      RBH for that FA appeared in the forage subset. The duodenal C17:0 flow increased
      with starch content and decreased with ruminal pH, respectively, whereas duodenal
      iso-C16:0 flow decreased with dietary NDF content for the seed/oil/fat subset.
      The duodenal C20:5n-3, C22:5n-3 and C22:6n-3 flows depended on their respective
      intake and the inhibitory effect of C22:6n-3 on duodenal C18:0 flow was
      quantified. Thirteen models of absorbed FA flows were performed depending on
      their respective duodenal flows. This study determined the effects of different
      qualitative and quantitative dietary and digestive factors, allowing for improved
      predictions of duodenal and absorbed FA flows.

PMID- 30105962
TI  - 7-Hydroxymatairesinol improves body weight, fat and sugar metabolism in C57BJ/6
      mice on a high-fat diet.
AB  - 7-Hydroxymatairesinol (7-HMR) is a plant lignan abundant in various
      concentrations in plant foods. The objective of this study was to test
      HMRLignanTM, a purified form of 7-HMR, and the corresponding Picea abies extract
      (total extract P. abies; TEP) as dietary supplements on a background of a high
      fat diet (HFD)-induced metabolic syndrome in mice and in the 3T3-L1 adipogenesis
      model. Mice, 3 weeks old, were fed a HFD for 60 d. Subgroups were treated with 3
      mg/kg body weight 7-HMR (HMRLignanTM) or 10 mg/kg body weight TEP by oral
      administration. 7-HMR and TEP limited the increase in body weight (-11 and -13 %)
      and fat mass (-11 and -18 %) in the HFD-fed mice. Epididymal adipocytes were 19
      and -12 % smaller and the liver was less steatotic (-62 and -65 %). Serum lipids
      decreased in TEP-treated mice (-11 % cholesterol, -23 % LDL and -15 % TAG) and
      sugar metabolism was ameliorated by both lignan preparations, as shown by a more
      than 70 % decrease in insulin secretion and insulin resistance. The expression of
      several metabolic genes was modulated by the HFD with an effect that was reversed
      by lignan. In 3T3-L1 cells, the 7-HMR metabolites enterolactone (ENL) and
      enterodiol (END) showed a 40 % inhibition of cell differentiation accompanied by
      the inhibited expression of the adipogenic genes PPARgamma, C/EBPalpha and aP2.
      Furthermore, END and ENL caused a 10 % reduction in TAG uptake in HEPA 1-6
      hepatoma cells. In conclusion, 7-HMR and TEP reduce metabolic imbalances typical
      of the metabolic syndrome and obesity in male mice, whereas their metabolites
      inhibit adipogenesis and lipid uptake in vitro.

PMID- 30105961
TI  - Serum fatty acids and progression from dengue fever to dengue haemorrhagic
      fever/dengue shock syndrome.
AB  - PUFA might modulate inflammatory responses involved in the development of severe
      dengue. We aimed to examine whether serum PUFA concentrations in patients
      diagnosed with dengue fever (DF) were related to the risk of progression to
      dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS). A secondary aim was to
      assess correlations between fatty acids (FA) and inflammatory biomarkers in
      patients with DF. We conducted a prospective case-control study nested within a
      cohort of patients who were diagnosed with DF and followed during the acute
      episode. We compared the distribution of individual FA (% of total FA) at onset
      of fever between 109 cases who progressed to DHF/DSS and 235 DF non-progressing
      controls using unconditional logistic regression. We estimated correlations
      between baseline FA and cytokine concentrations and compared FA concentrations
      between the acute episode and >1 year post-convalescence in a subgroup. DHA was
      positively related to progression to DHF/DSS (multivariable adjusted OR (AOR) for
      DHA in quintile 5 v. 1=5.34, 95 % CI 2.03, 14.1; P trend=0.007). Dihomo-gamma
      linolenic acid (DGLA) was inversely associated with progression (AOR for quintile
      5 v. 1=0.30, 95 % CI 0.13, 0.69; P trend=0.007). Pentadecanoic acid
      concentrations were inversely related to DHF/DSS. Correlations of PUFA with
      cytokines at baseline were low. PUFA were lower during the acute episode than in
      a disease-free period. In conclusion, serum DHA in patients with DF predicts
      higher odds of progression to DHF/DSS whereas DGLA and pentadecanoic acid predict
      lower odds.

PMID- 30105963
TI  - Genetic predisposition to salt-sensitive normotension and its effects on salt
      taste perception and intake.
AB  - Salt sensitivity is an independent CVD and mortality risk factor, which is
      present in both hypertensive and normotensive populations. It is genetically
      determined and it may affect the relationship between salt taste perception and
      salt intake. The aim of this study was to explore the genetic predisposition to
      salt sensitivity in a young and a middle-aged adult population and its effects on
      salt taste perception and salt intake. The effects of Na loading on blood
      pressure (BP) were investigated in twenty normotensive subjects and salt
      sensitivity defined as the change in BP after 7 d of low-Na (51.3 mmol Na/d) and
      7 d of high-Na diet (307.8 mmol Na/d). Salt taste perception was identified using
      the British Standards Institution sensory analysis method (BS ISO 3972:2011).
      Salt intake was assessed with a validated FFQ. DNA was genotyped for SNP in the
      SLC4A5, SCNN1B and TRPV1 genes. The subjects with AA genotype of the SLC4A5
      rs7571842 exhibited the highest increase in BP (? systolic BP=7.75 mmHg, P=0.002,
      d=2.4; ? diastolic BP=6.25 mmHg, P=0.044, d=1.3; ? mean arterial pressure=6.5
      mmHg, P=0.014, d=1.7). The SLC4A5 rs10177833 was associated with salt intake
      (P=0.037), and there was an association between salt taste perception and salt
      sensitivity (r s 0.551, P=0.041). In conclusion, there is a genetic
      predisposition to salt sensitivity and it is associated with salt taste
      perception. The association between salt taste perception and discretionary salt
      use suggests that preference for salty taste may be a driver of salt intake in a
      healthy population and warrants further investigation.

PMID- 30105966
TI  - Effect of a School-Based Hygiene Behavior Change Campaign on Handwashing with
      Soap in Bihar, India: Cluster-Randomized Trial.
AB  - Changing hand hygiene behavior at scale in the community remains a challenge. The
      objective of this study was to estimate the effect of Unilever's school-based
      "School of 5" handwashing campaign on handwashing with soap (HWWS) in
      schoolchildren and their mothers in the Indian state of Bihar. We conducted a
      cluster-randomized trial in two districts. We randomized a total of 32 villages
      with at least one eligible school to intervention and control groups (1:1) and
      recruited 338 households in each group for outcome measurement. We used
      structured observation in households to measure HWWS at target occasions (after
      defecation, soap use during bathing, and before each main meal) in schoolchildren
      and their mothers. Observers were blinded to intervention status. We observed 636
      target occasions (297 in the intervention arm and 339 in the control arm) in
      mothers and school-going children. After the intervention, HWWS prevalence at
      target occasions was 22.4% in the control arm and 26.6% in the intervention arm
      (prevalence difference +4.4%, 95% confidence interval: -4.0, 12.8). The
      difference was similar in children and mothers. Observers appeared to be
      adequately blinded to intervention status, whereas observed households were
      successfully kept unaware of the purpose of observations. To conclude, we found
      no evidence for a health-relevant effect of the School of 5 intervention on HWWS
      in schoolchildren and their mothers. Qualitative research suggested that reasons
      for the low impact of the intervention included low campaign intensity,
      ineffective delivery, and a model possibly not well tailored to these challenging
      physical and social environments.

PMID- 30105965
TI  - Recurrent Anthrax Outbreaks in Humans, Livestock, and Wildlife in the Same
      Locality, Kenya, 2014-2017.
AB  - Epidemiologic data indicate a global distribution of anthrax outbreaks associated
      with certain ecosystems that promote survival and viability of Bacillus anthracis
      spores. Here, we characterized three anthrax outbreaks involving humans,
      livestock, and wildlife that occurred in the same locality in Kenya between 2014
      and 2017. Clinical and epidemiologic data on the outbreaks were collected using
      active case finding and review of human, livestock, and wildlife health records.
      Information on temporal and spatial distribution of prior outbreaks in the area
      was collected using participatory epidemiology. The 2014-2017 outbreaks in Nakuru
      West subcounty affected 15 of 71 people who had contact with infected cattle
      (attack rate = 21.1%), including seven with gastrointestinal, six with cutaneous,
      and two with oropharyngeal forms of the disease. Two (13.3%) gastrointestinal
      human anthrax cases died. No human cases were associated with infected wildlife.
      Of the 54 cattle owned in 11 households affected, 20 died (attack rate = 37%).
      The 2015 outbreak resulted in death of 10.5% of the affected herbivorous wildlife
      at Lake Nakuru National Park, including 745 of 4,500 African buffaloes (species
      specific mortality rate = 17%) and three of 18 endangered white rhinos (species
      specific mortality rate = 16%). The species mortality rate ranged from 1% to 5%
      for the other affected wildlife species. Participatory epidemiology identified
      prior outbreaks between 1973 and 2011 in the same area. The frequency and
      severity of outbreaks in this area suggests that it is an anthrax hotspot ideal
      for investigating risk factors associated with long-term survival of anthrax
      spores and outbreak occurrence.

PMID- 30105964
TI  - Genetic Differentiation of Glossina pallidipes Tsetse Flies in Southern Kenya.
AB  - The tsetse fly Glossina pallidipes, the major vector of the parasite that causes
      animal African trypanosomiasis in Kenya, has been subject to intense control
      measures with only limited success. The G. pallidipes population dynamics and
      dispersal patterns that underlie limited success in vector control campaigns
      remain unresolved, and knowledge on genetic connectivity can provide insights,
      and thereby improve control and monitoring efforts. We therefore investigated the
      population structure and estimated migration and demographic parameters in G.
      pallidipes using genotypic data from 11 microsatellite loci scored in 250 tsetse
      flies collected from eight localities in Kenya. Clustering analysis identified
      two genetically distinct eastern and western clusters (mean between-cluster F ST
      = 0.202) separated by the Great Rift Valley. We also found evidence of admixture
      and migration between the eastern and western clusters, isolation by distance,
      and a widespread signal of inbreeding. We detected differences in population
      dynamics and dispersal patterns between the western and eastern clusters. These
      included lower genetic diversity (allelic richness; 7.48 versus 10.99), higher
      relatedness (percent related individuals; 21.4% versus 9.1%), and greater genetic
      differentiation (mean within-cluster F ST; 0.183 versus 0.018) in the western
      than the eastern cluster. Findings are consistent with the presence of smaller,
      less well-connected populations in Western relative to eastern Kenya. These data
      suggest that recent anthropogenic influences such as land use changes and vector
      control programs have influenced population dynamics in G. pallidipes in Kenya,
      and that vector control efforts should include some region-specific strategies to
      effectively control this disease vector.

PMID- 30105968
TI  - Chromobacterium violaceum in Northern Australia: A Sheep in Wolf's Clothing?
AB  - In many parts of the world, the case-fatality rate of Chromobacterium violaceum
      infection approaches 60%. To evaluate the spectrum of disease associated with C.
      violaceum in Far North Queensland (FNQ), Australia, we reviewed all culture
      confirmed isolates from 1997 to 2017. There were 28 isolates, 15 represented
      infection, 11 were contaminants, and two charts were destroyed preventing
      detailed evaluation of these cases. The most common sites of infection were the
      skin and soft tissue and the urinary tract; there were two cases of bacteremia
      without focus. There were no deaths attributable to C. violaceum during the study
      period and only two cases required intensive care unit support, although in both
      patients this was not for the C. violaceum infection, but for the management of
      other health issues. Globally, C. violaceum has a reputation as a deadly
      pathogen, but in FNQ, Australia, infections usually follow a relatively benign
      course.

PMID- 30105967
TI  - Molecular Detection of Residual Parasitemia after Pyronaridine-Artesunate or
      Artemether-Lumefantrine Treatment of Uncomplicated Plasmodium falciparum Malaria
      in Kenyan Children.
AB  - Artemisinin resistance is rapidly rising in Southeast Asia and may spread to
      African countries, where efficacy estimates are currently still excellent.
      Extensive monitoring of parasite clearance dynamics after treatment is needed to
      determine whether responsiveness to artemisinin-based combination therapies (ACT)
      is changing in Africa. In this study, Kenyan children with uncomplicated
      falciparum malaria were randomly assigned to pyronaridine-artesunate (PA) or
      artemether-lumefantrine (AL) treatment. Parasite clearance was evaluated over 7
      days following the start of treatment by quantitative polymerase chain reaction
      (qPCR) and direct-on-blood PCR nucleic acid lateral flow immunoassay (db-PCR
      NALFIA), a simplified molecular malaria diagnostic. Residual parasitemia at day 7
      was detected by qPCR in 37.1% (26/70) of AL-treated children and in 46.1% (35/76)
      of PA-treated participants (P = 0.275). Direct-on-blood PCR nucleic acid lateral
      flow immunoassay detected residual parasites at day 7 in 33.3% (23/69) and 30.3%
      (23/76) of AL and PA-treated participants, respectively (P = 0.692). qPCR
      determined parasitemia at day 7 was associated with increased prevalence and
      density of gametocytes at baseline (P = 0.014 and P = 0.003, for prevalence and
      density, respectively) and during follow-up (P = 0.007 and P = 0.011,
      respectively, at day 7). A positive db-PCR-NALFIA outcome at day 7 was associated
      with treatment failure (odds ratio [OR]: 3.410, 95% confidence interval [CI]:
      1.513-7.689, P = 0.003), but this association was not found for qPCR (OR: 0.701,
      95% CI: 0.312-1.578, P = 0.391). Both qPCR and db-PCR-NALFIA detected substantial
      residual submicroscopic parasitemia after microscopically successful PA and AL
      treatment and can be useful tools to monitor parasite clearance. To predict
      treatment outcome, db-PCR-NALFIA may be more suitable than qPCR.

PMID- 30105969
TI  - Bovine macrophage-derived extracellular traps act as early effectors against the
      abortive parasite Neospora caninum.
AB  - Macrophages are multipurpose phagocytes and are considered to be irreplaceable
      during the early host innate immune response against microbial and parasitic
      pathogens. However, no report has investigated the novel anti-parasitic mechanism
      of macrophage-derived extracellular traps (ETs) against the abortive apicomplexan
      parasite Neospora caninum (N. caninum) in cattle. Scanning electron microscopy
      (SEM) was used to visualize and characterize N. caninum tachyzoite-induced
      macrophage-triggered ETs in exposed bovine macrophages. Fluorescence confocal
      microscopy was used to confirm the classical backbone structure of DNA embedded
      with histone 3 (H3) and myeloperoxidase (MPO) in N. caninum tachyzoite-induced
      macrophage-derived ETs. Furthermore, the lactate dehydrogenase (LDH) levels in
      the supernatants of parasite-exposed macrophages were detected by a LDH
      Cytotoxicity Assay(r) kit. The results clearly demonstrated that N. caninum
      tachyzoites triggered bovine macrophage-derived ET-like structures. Inhibiting
      assays revealed that N. caninum tachyzoite-induced macrophage-mediated ET
      formation may be an ERK 1/2- and p38 MAPK-dependent cell death process. In
      conclusion, the present study is the first report on the formation of ETs in
      bovine macrophages against N. caninum tachyzoites and adds new data on the
      possible role of macrophages in vivo infection by capturing invasive stages and
      exposing them to other leukocytes.

PMID- 30105970
TI  - Immune response and protective efficacy of Eimeria tenella recombinant refractile
      body protein, EtSO7, in chickens.
AB  - Refractile body protein, SO7, is a highly immunogenic protein which is
      essentially involved in the early development of Eimeria species infecting the
      domestic chicken. In the present study, the immune response and protective
      efficacy of recombinant Eimeria tenella SO7 (rEtSO7) protein was assessed in
      broiler chickens following homologous oocyst challenge. Broiler chicks were
      subcutaneously immunized with rEtSO7 antigen adjuvanted with Montanide ISA 71 VG
      on 7 and 21 days of age and protective efficacy of vaccination was evaluated in
      terms of body weight gain, lesion score and reduction in oocyst output. The
      peripheral blood lymphocyte proliferation, serum IgY response, and levels of
      interferon gamma (IFN-gamma), interleukin 2 (IL-2), interleukin 4 (IL-4), tumor
      growth factor beta (TGF-beta) and nitric oxide (NO) were assessed. The results
      revealed significant reduction (p < 0.05) in the oocyst output and increased
      weight gain in immunized birds as compared to unimmunized birds. Significantly
      increased levels of serum IgY, IFN-gamma and proliferation of lymphocytes were
      evident in rEtSO7 immunized chickens. The results demonstrated that the
      recombinant protein could effectively elicit the cellular and humoral immune
      responses in immunized chickens, and provided significant protection against
      caecal coccidiosis in chickens.

PMID- 30105971
TI  - The molecular characterization and protective efficacy of microneme 3 of Eimeria
      mitis in chickens.
AB  - E. mitis is ubiquitous in clinical coccidiosis caused by mixed infection of
      Eimeria species and the infection by E. mitis usually significantly impairs
      productivity of the infected chickens. To date, however, few protective antigens
      from E. mitis have been reported. In this study, the molecular characterization
      and protective efficacy of microneme 3 of Eimeria mitis (EmiMIC3) were analyzed.
      EmiMIC3 gene was cloned from sporozoites of E. mitis and its MARs (microneme
      adhesive repeats domain) were predicted. Recombinant EmiMIC3 (rEmiMIC3) was
      expressed in E. coli and purified and then was analyzed by western blot with anti
      E. mitis chicken serum. Meanwhile, native EmiMIC3 from sporozoites was analyzed
      by anti-rEmiMIC3 rat serum. The expressions of EmiMIC3 in E. mitis sporozoites
      and merozoites were analyzed by immunofluorescence assay. The rEmiMIC3-induced
      changes of T lymphocytes subpopulation, serum cytokines and IgY levels and the
      protective efficacy of rEmiMIC3 were determined in animal experiments. The
      results showed that the deduced open reading frame (ORF) of EmiMIC3 was composed
      of 1145 amino acids, possessing 9 MARs. EmiMIC3 gene was submitted to GenBank
      (accession number: MG888670). EmiMIC3 could express in sporozoites and merozoites
      respectively and located at the apex of E. mitis sporozoite. Western blot assay
      revealed that the rEmiMIC3 could be recognized by serum of chicken infected by E.
      mitis and the native EmiMIC3 from sporozoites could also be recognized by rat
      serum against rEmiMIC3. Following vaccination with rEmiMIC3, higher levels of IL
      10, IFN-gamma, TGF-betaand IL-17, higher proportions of CD4+/CD3+ and CD8+/CD3 +
      T lymphocytes and higher level of IgY antibody were induced compared to the
      controls. Vaccination with rEmiMIC3 prominently increased the weight gains and
      decreased oocyst output of the vaccinated chickens after challenge infection. Our
      result not only enriches protective candidate antigen of E. mitis, but also
      provides available protective antigen of E. mitis for the development of
      multivalent vaccines against infection caused by mixture of Eimeria species in
      clinical coccidiosis.

PMID- 30105972
TI  - Field evaluation of Duddingtonia flagrans IAH 1297 for the reduction of worm
      burden in grazing animals: Pasture larval studies in horses, cattle and goats.
AB  - A series of placebo-controlled trials were conducted in horses, cattle and goats
      in different seasons and bioclimatic regions of New South Wales and Queensland,
      Australia, to evaluate the ability of BioWorma(r), a feed supplement containing
      the spores of Duddingtonia flagrans IAH 1297, to reduce the larval development of
      parasitic gastrointestinal nematodes (GIN) and their subsequent migration from
      faeces onto the surrounding pasture. In each trial, faeces were collected from
      animals harbouring a burden of nematode parasites following a period of
      supplementation with a placebo and again after supplementation with BioWorma. The
      faeces were manually placed onto pasture plots at one or two distinct
      geographical sites and the effect of treatment was determined by subsequent
      monitoring the numbers of parasitic larvae on the pasture surrounding the faecal
      pats at two weekly intervals over an eight week period. The results for these
      studies showed that administration of BioWorma at a minimum daily dose of 3 * 104
      spores/kg bodyweight reduced parasite larvae in the pasture surrounding the
      faeces by 53-99 % over an eight week post treatment period in horses, cattle and
      goats in a range of bioclimatic zones and in different seasons. Overall, the
      studies with BioWorma show substantial reductions in GIN infectivity of pasture
      surrounding faeces of treated horses, cattle and goats (P < 0.05). Results
      indicate that the use of BioWorma in these host species would lead to decreased
      levels of GIN infection in animals grazing pasture when this product is used and
      would provide an alternative means of controlling parasitic nematodes.

PMID- 30105974
TI  - A novel recombinase polymerase amplification (RPA) assay for the rapid isothermal
      detection of Neospora caninum in aborted bovine fetuses.
AB  - The development of a method to rapidly diagnose Neospora caninum infection is
      highly desirable. Recombinase polymerase amplification (RPA), combined with
      lateral flow (LF) strips, is a novel approach to rapidly amplify and visualize
      DNA. We have developed a prototype LF-RPA assay, using primers and a probe that
      targeted a specific sequence in the N. caninum NC-5 gene. The N. caninum-specific
      LF-RPA assay was first tested on purified DNA from oocysts and amplified N.
      caninum DNA to detectable levels in 10 min, at a constant temperature and without
      the need for an expensive thermocycler. The designed RPA primers and probe
      displayed 100% specificity for detecting N. caninum without any cross-reaction
      with DNA from nine related protozoan spp. (eg Toxoplasma gondii, Sarcocystis
      gigantean, Sarcocystis zuoi, Hammondia hammondi, Hammondia heydorni, Eimeria
      cylindrica, Plasmodium falciparum, Theileria annulata and Babesia bigemina).
      Although, LF-RPA assay detected amounts as low as 50 fg of N. caninum DNA, it was
      nearly 5-fold less sensitive than previously published qPCR and nested PCR
      assays. We tested the diagnostic performance of the LF-RPA assay for the
      detection of N. caninum DNA in aborted bovine fetal tissue samples, and compared
      the results with those obtained from nested PCR. Out of the 75 samples examined,
      18 (24%) and 17 (22.6%) tested positive using LF-RPA and nested PCR,
      respectively. Our results indicate that LF-RPA is a suitable assay for the rapid
      and reliable detection of N. caninum.

PMID- 30105973
TI  - Intranasal delivery of a formulation containing stage-specific recombinant
      proteins of Fasciola hepatica cathepsin L5 and cathepsin B2 triggers an anti
      fecundity effect and an adjuvant-mediated reduction in fluke burden in sheep.
AB  - Fasciola hepatica infection continues to be a major problem in the agriculture
      sector, particularly in sheep and cattle. Cathepsin L and B proteases are major
      components of the excretory/secretory material of the parasite, and their roles
      in several important aspects of parasite invasion and survival has led to their
      use as targets in rational vaccine design. Previous studies in rats demonstrated
      that the use of stage-specific antigens, cathepsin B2 and cathepsin L5, as part
      of a multivalent vaccine, was able to confer significant protection against
      challenge. In the present study, recombinant versions of cathepsin L5 and
      cathepsin B2 produced in yeast were used in combination to vaccinate sheep.
      Intramuscular and intranasal forms of administration were applied, and sheep were
      subsequently challenged with 150 F. hepatica metacercariae. Intramuscular
      vaccination was able to induce a strong systemic antibody response against both
      antigens, but failed to confer significant protection. Conversely, no elevated
      antibody response was detected against the vaccine antigens following nasal
      vaccination; however, a reduction in parasite egg viability (>92%) and a
      statistically significant (p = 0.006), predominantly adjuvant-mediated reduction
      in worm burdens was observed.

PMID- 30105975
TI  - Eimeria tenella infection perturbs the chicken gut microbiota from the onset of
      oocyst shedding.
AB  - Coccidiosis is a serious threat to the poultry industry, resulting in substantial
      economic losses worldwide. The effective development of alternative treatments
      for coccidiosis that does not involve chemotherapy drugs and does not result in
      antibiotic resistance relies on gaining a clearer understanding of the
      interaction between host intestinal microbiota and enteric coccidia. Here, we
      established an Eimeria tenella infection model in chickens and subsequently
      monitored the changes in the overall intestinal microbiome using 16S rRNA gene
      sequencing. We found that the gut (i.e. fecal) microbiota of infected chicken
      differed from that of uninfected naive animals. Levels of non-pathogenic
      bacteria, including Lactobacillus and Faecalibacterium declined, whereas those of
      pathogenic bacteria, including Clostridium, Lysinibacillus, and Escherichia,
      increased over time in response to E. tenella infection. Similar dynamic changes
      of the fecal microbiota were observed in both Arbor Acres broilers and White
      Leghorn chickens, indicating that the perturbation of the microbiota was directly
      induced by E. tenella infection. Our findings could be used to further elucidate
      the serious damage to host health caused by coccidia infection, leading to the
      development of new effective treatment options for coccidiosis.

PMID- 30105977
TI  - Low allelic diversity in vaccine candidates genes from different locations
      sustain hope for Fasciola hepatica immunization.
AB  - Fasciola hepatica is a trematode parasite that causes fasciolosis in animals and
      humans. Fasciolosis is usually treated with triclabendazole, although drug
      resistant parasites have been described in several geographical locations. An
      alternative to drug treatment would be the use of a vaccine, although vaccination
      studies that have been performed mainly in ruminants over the last 30 years, show
      high variability in the achieved protection and are not yet ready for
      commercialisation. Since F. hepatica exhibits a high degree of genomic
      polymorphism, variation in vaccine efficacy could be attributed, at least
      partially, to phenotypic differences in vaccine candidate sequences amongst
      parasites used in the challenge infections. To begin to address this issue, a
      collection of F. hepatica isolates from geographically dispersed regions, as well
      as parasites obtained from vaccination trials performed against a field isolate
      from Uruguay and the experimentally maintained South Gloucester isolate (Ridgeway
      Research, UK), were compiled to establish a F. hepatica Biobank. These collected
      isolates were used for the genetic analysis of several vaccine candidates that
      are important in host-parasite interactions and are the focus of the H2020
      PARAGONE vaccine project (https://www.paragoneh2020.eu/), namely FhCL1, FhCL2,
      FhPrx, FhLAP and FhHDM. Our results show that F. hepatica exhibits a high level
      of conservation in the sequences encoding each of these proteins. The
      consequential low variability in these vaccine candidates amongst parasites from
      different geographical regions reinforces the idea that they would be suitable
      immunogens against liver fluke isolates worldwide.

PMID- 30105976
TI  - An efficient rearing system rapidly producing large quantities of poultry red
      mites, Dermanyssus gallinae (Acari: Dermanyssidae), under laboratory conditions.
AB  - The poultry red mite, Dermanyssus gallinae, is one of the most economically
      deleterious ectoparasites affecting egg-laying hens in many parts of the world.
      New approaches to control D. gallinae often require the maintenance of colonies
      of D. gallinae under laboratory conditions. In the present study, we present an
      efficient rearing system for D. gallinae, consisting of a metal cage, a plastic
      storage box and a tray filled with water. Chicks were raised in the cage as host
      animals. A novel trap was developed to monitor the dynamic changes of mite
      populations, made with a plastic centrifuge tube and a disposable breathing mask
      with folds. Mite parameters were analyzed, including number of mites and eggs,
      survival and feeding rates, oviposition, hatchability and the proportion of D.
      gallinae at different life stages. The results show that the rearing system had a
      53.5-fold increase in the number of mites over a period of six weeks after the
      introduction of mites. The survival rates of mites were above 94%, and the mean
      feeding rates ranged from 22.57% to 37.30%. The mean number of eggs per female
      ranged from 3.42 to 3.50, with the hatchability of eggs above 97%. Nymphs made up
      most of the population, ranging from 71.46% to 81.37%, while the population of
      larvae was minor and ranging from 7.54% to 13.04%. The mask trap used in this
      study was an effective and convenient device to shelter D. gallinae and monitor
      the dynamic changes of the mite population. The rearing system proved very
      effective in maintaining and reproducing colonies of D. gallinae, with great
      potential for the evaluation of the efficacy of vaccines or compounds against D.
      gallinae under laboratory conditions. It would be a useful tool for close
      observations in studies on the biology, acology and physiology of poultry red
      mites.

PMID- 30105978
TI  - Efficacy of spinosad on the treatment of myiasis caused by Cochliomyia
      hominivorax (Diptera: Calliphoridae) in dogs.
AB  - The purpose of this study was to evaluate the overall efficacy, larval expulsion
      and larvicidal effect of spinosad on the treatment of myiasis caused by New World
      screwworm Cochliomyia hominivorax in naturally infested dogs. Six Beagle dogs
      presenting with myiasis were treated once with spinosad 560 mg, with dosages
      ranging from 43 to 577 mg/kg. Dogs were observed with 15 min post treatment, and
      with intervals of 15 min within the first hour followed by hourly evaluations up
      to six hours post-treatment. After this period, the remaining larvae were
      mechanically removed. Spontaneous expulsion of larvae was variable among dogs.
      All dogs received support treatment and were followed up for healing of the
      myiasis-associated lesion. On average, the highest larval expulsion occurred four
      hours after treatment. A single spinosad treatment had an overall efficacy of
      79.7% (56.7-100%). The average larval expulsion rate was 73.3% (56.7-100%),
      reached its maximum within 6 h post-treatment, and the average larvicidal effect
      was only 23.7% (0-58.3%). No animal needed a second dosage 24 h post-treatment,
      lesions were completely healed within 8 days post-treatment. Despite not reaching
      the desirable 100% efficacy, spinosad treatment is an option in managing NSW
      myiasis, in conjunction with mechanical removal of maggots that remain in the
      lesion and support treatment.

PMID- 30105979
TI  - Development and application of a recombinant protein-based indirect ELISA for the
      detection of serum antibodies against Cystoisospora suis in swine.
AB  - The apicomplexan parasite Cystoisospora suis which causes neonatal porcine
      coccidiosis is one of the predominant parasite in suckling piglets. Currently,
      the immunofluorescence antibody test (IFAT) is the only available serological
      tool for detecting serum antibodies against C. suis which has several
      limitations, including bias from interpretation and low throughput. In the
      present study, an indirect enzyme-linked immunosorbent assay (ELISA) was
      developed using a previously characterized recombinant merozoite protein for the
      detection of specific immunoglobulin G (IgG) and IgA against C. suis. The
      recombinant protein was expressed in Escherichia coli as a N-terminal histidine
      fusion protein, and its specificity was confirmed in an immunoblot probed with
      highly positive anti-C. suis sera from experimentally infected piglets. Optimal
      dilutions of recombinant protein, sera and conjugate were determined by
      checkerboard titrations, and the serum dilution that gave the greatest ratio
      between the positive and the negative sera was selected for subsequent analyses.
      Agreement between the IFAT and the newly developed ELISA was assessed with kappa
      statistics. The receiver operating characteristic (ROC) curve analysis based on
      185 serum samples with known C. suis exposure previously tested in the reference
      IFAT was used to determine the cut-off value, sensitivity and specificity of the
      ELISA. For IgG, the ELISA had an estimated cut-off value of 0.82 and sensitivity
      and specificity values of 94.7% and 98%, respectively, whereas for IgA the
      estimated cut-off value was 0.41 and sensitivity and specificity values were
      both100%. According to kappa coefficient, an excellent correlation (kappa > 0.8)
      was found between IFAT and ELISA for both isotypes. The diagnostic accuracy of
      the test measured as the area under the ROC curve index scaled between 0.98 and
      1.0, indicating high discriminatory capacity and its possible application as a
      serological tool for detecting antibody response in the host following C. suis
      exposure/immunization and large-scale surveillance studies.

PMID- 30105980
TI  - Population genetic structure of the parasitic nematode Spirocerca lupi in South
      Africa.
AB  - Spirocerca lupi is a parasitic nematode of canids and occurs in most tropical and
      subtropical regions around the world. While its life cycle is well known, insight
      is lacking about its mating structure within-hosts, genetic variability and long
      distance dispersal ability. These characteristics contribute significantly to the
      dynamics and spread of potential resistance genes, which impacts on the control
      of S. lupi. To evaluate the population structure and infer potential mating
      behaviour of S. lupi, we genotyped 130 samples at nine microsatellite loci from
      three geographical locations in South Africa, between 600 and 1000 km apart.
      These loci identified unique individuals with high levels of polymorphism
      suggesting that these are not newly established S. lupi populations in South
      Africa and that effective population sizes must be large. Population genetic
      analyses showed that populations are not very distinct, that worms within dogs
      are more similar to each other than random worms from each population, and that
      mating is at random within dogs. We can thus infer that the parasite is
      frequently transported over great distances. Even so, two genetically distinct
      populations could be identified. Relatedness of worms within dogs were
      significantly higher than between dogs and together with F-statistics suggests
      some non-random transmission of parasites between hosts. While mating is random
      within a host, parasites from a host are more likely to be related and hence an
      increase in homozygosity is seen. The implications of this genetic structure on
      parasite control are considered.

PMID- 30105981
TI  - Occurrence and genetic diversity of Blastocystis in Korean cattle.
AB  - Blastocystis is one of the most commonly detected intestinal protozoan parasites
      worldwide and has been found in humans and other animals. Therefore, many
      countries have actively researched this parasite. However, to our knowledge, no
      study of Blastocystis has been conducted in Korea. Therefore, we conducted a
      study of the current status of Blastocystis infection in domestic cattle, the
      various genotypes involved, and its zoonotic potential through a phylogenetic
      comparison with subtypes found in other studies. The feces of cattle were
      randomly collected throughout Korea; basic information, including collection
      date, sex, and cattle type was recorded, and DNA extraction, PCR, and
      phylogenetic analyses were performed. A total of 1,512 fecal samples were tested.
      The 101 Blastocystis-positive samples were obtained, yielding an approximate
      infection rate of 6.7%. Differences in age, cattle type, fecal type, and season
      were statistically significant between Blastocystis-positive and -negative
      cattle. In this study, four subtypes of Blastocystis (ST1, ST5, ST10, and ST14)
      were confirmed by phylogenetic analysis. ST1 and ST5 are potential zoonotic
      subtypes, therefore the possibility of zoonotic transmission cannot be ignored.
      Further research and clarification of the infection and transmission patterns of
      Blastocystis are warranted.

PMID- 30105982
TI  - Detection of Toxoplasma gondii in three common bottlenose dolphins (Tursiops
      truncatus); A first description from the Eastern Mediterranean Sea.
AB  - Toxoplasma gondii has been described in several marine mammals around the world
      including numerous species of cetaceans, yet infection and transmission
      mechanisms in the marine environment are not clearly defined. The Israel Marine
      Mammal Research and Assistance Center has been collating a database of all marine
      mammal stranding events along the country's national coastlines since 1993. In
      this study, we describe the molecular detection and characterisation of T. gondii
      in three common bottlenose dolphins (Tursiops truncatus) including one case of
      coinfection with herpesvirus. The animals were found stranded on the
      Mediterranean coast of Israel in May and November 2013. In one of the three
      cases, the dolphin was found alive and admitted to intensive care. To our
      knowledge, this is the first report of T. gondii infection of marine mammals in
      the Eastern Mediterranean Sea. As this parasite acts as an indicator for marine
      pollution and marine mammal health, we believe these findings add important
      information regarding the state of the environment in this region.

PMID- 30105984
TI  - Live weight as a basis for targeted selective treatment of lambs post-weaning.
AB  - Targeted selective treatment (TST) has been proposed as a sustainable method of
      gastrointestinal nematode control that reduces the number of anthelmintic
      treatments administered, thereby preserving a susceptible nematode population in
      refugia. In order to minimise the impact of withholding treatment on animal
      performance, animals that would benefit most should be selected for treatment.
      However, the most suitable criteria for selecting which animals to treat remain a
      subject of research. The impact of implementing a TST strategy based on lamb live
      weight was investigated, and whether heavy lambs were more resilient than light
      lambs if left untreated. The study was conducted using weaned lambs on 3 sheep
      farms, and over 2 years. On each farm lambs were weighed and divided into heavy,
      medium and light weight classes. Within the heavy (n = 225) and light (n = 218)
      weight classes lambs were randomly allocated to two treatments; anthelmintic
      treatment or no anthelmintic treatment. All lambs in the medium weight class were
      treated. Animal performance and parasitological parameters were assessed over a
      28-day period. Anthelmintic treatment had a significant effect (P < 0.01) on
      faecal egg count, average daily weight gain, body condition score and dag score;
      there was no treatment by weight class interaction. Anthelmintic treatment had no
      effect on plasma pepsinogen concentration or on blood leukocyte numbers.
      Withholding anthelmintic treatment from lambs therefore had a negative effect on
      worm egg count and animal performance with no evidence that heavy lambs were more
      resilient than light lambs when left untreated.

PMID- 30105983
TI  - Hidden in plain sight - Multiple resistant species within a strongyle community.
AB  - Ovine parasitic gastroenteritis is a complex disease routinely treated using
      anthelmintics. Although many different strongyle species may contribute to
      parasitic gastroenteritis, not all are equally pathogenic: in temperate regions,
      the primary pathogen is Teladorsagia circumcincta. In this study we investigated
      benzimidazole and ivermectin resistance on a commercial sheep farm in southeast
      Scotland. We assessed the impact of species diversity on the diagnosis of
      resistance using the faecal egg count reduction test and in vitro bioassays, and
      correlated the results with the frequency of benzimidazole resistance-associated
      genotypes measured in the T. circumcincta population by pyrosequencing of the
      beta-tubulin isotype-1 gene. Faecal egg count reduction test results showed
      efficacies of 65% for albendazole and 77% for ivermectin, indicating moderate
      resistance levels on the farm. However, PCR speciation of the same populations
      pre- and post-treatment revealed that removal of susceptible species had masked
      the presence of a highly resistant population of T. circumcincta. Less than 25%
      of individuals in the pre-treatment populations were T. circumcincta, the
      remainder consisting of Cooperia curticei, Chabertia ovina, Oesophagostomum
      venulosum and Trichostrongylus spp. In contrast, post-treatment with albendazole
      or ivermectin, the majority (88% and 100% respectively) of the populations
      consisted of T. circumcincta. The egg hatch test for benzimidazole resistance and
      the larval development test for ivermectin resistance were carried out using eggs
      obtained from the same populations and the results were broadly consistent with
      the faecal egg count reduction test. Thirty individual T. circumcincta from each
      sampling time point were assessed for benzimidazole resistance by pyrosequencing,
      revealing a high frequency and diversity of resistance-associated mutations,
      including within the population sampled post-ivermectin treatment. These results
      highlight the potential diversity of parasite species present on UK farms, and
      their importance in the diagnosis of anthelmintic resistance. On this particular
      farm, we demonstrate the presence of a highly dual-resistant population of T.
      circumcincta, which was strongly selected by treatment with either benzimidazoles
      or ivermectin, while other potentially less pathogenic species were removed.

PMID- 30105987
TI  - Lichenoid dermatoses in hospitals in Lome, Togo: 959 cases.
AB  - The aim of this study was to describe the epidemiologic, clinical, and
      therapeutic profiles of cases of lichenoid dermatosis in Lome, together with
      their outcomes. This retrospective descriptive study reviewed records of patients
      receiving care for lichenoid dermatosis from January 1997 to December 2016 in the
      dermatology departments of Lome. In total, 959 (2.2%) cases of lichenoid
      dermatoses including 813 (84.8%) of lichen planus and 123 (12.8%) of lichen
      striatus were recorded. The mean age of the patients was 29.60 +/- 14 years and
      the sex ratio (M/F) was 0.7. Lichen planus was papular and found most often on
      the lower limbs (56.0%). Lichen striatus was banded along the lines of Blaschko,
      mainly on the lower limbs (55.3%). There were 23 patients with lichen nitidus
      lesions, most often on the trunk (47.8%). The treatment was based on
      corticosteroid therapy. Recurrences were noted in 40 (11.6%) cases of lichen
      planus and 4 (3.2%) of lichen striatus. This study shows that the principal
      lichenoid dermatoses in Lome are lichen planus, and their management is based on
      corticosteroid treatment.

PMID- 30105986
TI  - Evaluation of an 11.2% spinetoram topical spot-on solution for the control of
      experimental and natural flea (Ctenocephalides felis) infestations on cats in
      Europe.
AB  - Spinetoram is the newest member the spinosyn-class of natural products to be
      commercialized for flea control on cats in the United States under the tradename
      Cheristin(r) for cats. This report describes results from two laboratory studies
      and a multi-center clinical field trial designed to confirm the efficacy of a
      topical spot-on solution containing spinetoram (11.2% w/w, 130 mg/mL) against
      European strains of the cat flea, Ctenocephalides felis. In the laboratory
      studies, cats were allocated to one of two treatment groups of eight animals
      each: negative control (mineral oil) or spinetoram, both applied as a topical
      spot-on at the base of the skull on Day 0. Cats were infested with ~100 newly
      emerged, unfed adult fleas on Days -2 or -1, 7, 14, 21, 28 and 35. To calculate
      efficacy, fleas were counted and removed 48 h after treatment, and 48 h after
      each subsequent infestation through week 5. Spinetoram treatments provided 100%
      efficacy through at least day 16 and >= 97% efficacy (arithmetic mean) for one
      month. For the field trial, 23 clinics from Northern and Southern Europe
      participated in the study that compared the effectiveness and safety of
      spinetoram and fipronil/(S)-methoprene treatments over a period of two months.
      There were 258 and 248 evaluable efficacy cases for month 1 and month 2,
      respectively, with 300 total evaluable cases for safety. Treatments were
      administered on Day 0 and again on Day 30 (+/-3 days). The effectiveness of
      treatments was calculated based on reduction in live flea counts on Days 14, 30,
      44 and 60 (+/-3 days) relative to flea counts obtained on Day 0. Efficacy
      (geometric mean percent flea reduction) on Days 14, 30, 44 and 60 was 97.0%,
      95.0%, 99.3% and 99.1% for spinetoram, respectively, and 86.1%, 80.9%, 92.4% and
      92.3% for fipronil/(S)-methoprene, respectively. Spinetoram was deemed non
      inferior at all intervals and superior to fipronil/(S)-methoprene at Days 30 and
      60. Clinical signs of flea allergy dermatitis (FAD) were markedly improved
      following spinetoram treatment, as demonstrated through statistically significant
      reductions in severity of FAD scores for most of the clinical signs when compared
      to fipronil/(S)-methoprene treatment. There was a lower overall adverse event
      incidence rate for spinetoram (5.1%) versus fipronil/(S)-methoprene treatment
      (11.5%).

PMID- 30105988
TI  - Angiosarcoma-related pneumohemothorax treated with intrapleural paclitaxel
      administration and pleurodesis with OK-432.

PMID- 30105989
TI  - Application of electrochemotherapy in the management of primary and metastatic
      cutaneous malignant tumours: a systematic review and meta-analysis.
AB  - Electrochemotherapy is becoming a promising technique for the management of
      malignancies of skin and non-skin origin. The current review aims to clarify
      current knowledge on administration of electrochemotherapy for the treatment of
      various skin tumours. A systematic literature search was performed, up to the end
      of 2016, on studies in which the application of electrochemotherapy for
      management of primary and metastatic cutaneous malignant tumours was assessed.
      Having selected appropriate studies, pooled estimates of mean objective
      (complete) responses, with 95% confidence intervals (CIs), were calculated to
      assess treatment efficacy. Finally, the main emerging themes from the papers were
      discussed in more detail. From 465 records identified through database searching,
      a total of 128 studies were screened, of which 70 were included for review. After
      a pooled analysis, the estimate for mean objective response following
      electrochemotherapy was 84.02% (95% CI: 80.08-87.61). Furthermore, the pooled
      estimate of objective treatment response of evaluated studies was 83.91% (95% CI:
      79.15-88.17%) for bleomycin and 80.82% (95% CI: 66.00-92.36%) for cisplatin.
      Electrochemotherapy is a feasible, inexpensive, fast and easy technique to
      perform local treatment, regardless of tumour type, with a low level of adverse
      effects and patient discomfort. This method can be applied alone for patients
      with primary cutaneous lesions, or local or locoregional metastases, or as an
      additional treatment modality in patients with distant metastases.

PMID- 30105985
TI  - Does selection for growth rate in broilers affect their resistance and tolerance
      to Eimeria maxima?
AB  - Chickens exhibit varied responses to infection with Eimeria parasites. We
      hypothesise that broilers selected for increased growth rate will show lower
      resistance and tolerance to a coccidian challenge. 288 chickens of fast (F) or
      slow (S) growing lines were inoculated with 0 (control), 2500 (low-dose), or 7000
      (high-dose) sporulated E. maxima oocysts at 13 days of age in two consecutive
      rounds. Gain and Intake were measured daily and their values relative to BW at
      the point of infection were calculated over the pre-patent (days 1-4 post
      infection), acute (d5-8 pi), and recovery (d9-12 pi) phases of infection to
      assess the impact of infection. Levels of plasma carotenoids, vitamins E and A,
      long bone mineralisation, caecal microbiota diversity indices, and histological
      measurements were assessed at the acute (d6 pi) and recovery stage (d13 pi). In
      addition, we measured the levels of nitric oxide metabolites and the number of
      parasite genome copies in the jejunumat d6pi. In absolute terms F birds grew 1.42
      times faster than S birds when not infected. Infection significantly reduced
      relative daily gain and intake (P < 0.001), with the effects being most
      pronounced during the acute phase (P < 0.001). Levels of all metabolites were
      significantly decreased, apart from NO which increased (P < 0.001) in response to
      infection on d6pi, and were accompanied by changes in histomorphometric features
      and the presence of E. maxima genome copies in infected birds, which persisted to
      d13pi. Furthermore, infection reduced tibia and femur mineralisation, which also
      persisted to d13pi. Reductions in measured variables were mostly independent of
      dose size, as was the level of parasite replication. The impact of infection was
      similar for S and F-line birds for all measured parameters, and there were no
      significant interactions between line x dose size on any of these parameters. In
      conclusion, our results suggest that line differences in productive performance
      do not influence host responses to coccidiosis when offered nutrient adequate
      diets.

PMID- 30105990
TI  - Coexistence of Kaposi's sarcoma and psoriasis: is there a hidden relationship?
AB  - The relationship between Kaposi's sarcoma (KS) and psoriasis is still
      controversial. To analyse the association between KS and psoriasis, address the
      hypothesis of a reciprocal influence between the two conditions relative to
      clinical presentation and evolution, and consider the best therapeutic approach
      to be used for the treatment of psoriasis in KS patients in order to avoid the
      typical induction or worsening of KS during immunosuppression. We retrospectively
      reviewed clinical records of 37 patients with KS and psoriasis. Fisher's exact
      test was performed in order to compare epidemiological and clinical data between
      subsets of patients. The prevalence of psoriasis in our KS population (n = 1407)
      was 2.6%. There were no statistically significant differences in terms of stage
      or rate of progression between KS patients with and without psoriasis, except for
      a higher frequency of patients with KS Stage IIB among patients with KS and
      psoriasis (p = 0.001). Patients with psoriasis have a risk of KS comparable to
      that of the general population. Psoriasis and KS do not appear to influence each
      other. For the treatment of psoriasis in KS patients, one should take into
      account the KS-inducing potential of certain anti-psoriatic drugs.

PMID- 30105992
TI  - Mutations in the gamma-secretase genes PSEN1, PSENEN, and NCSTN in a family with
      acne inversa.

PMID- 30105991
TI  - Comparable efficacy of adapalene 0.3% gel and tretinoin 0.05% cream as treatment
      for cutaneous photoaging.
AB  - BACKGROUND: Adapalene has been previously evaluated as a treatment for actinic
      keratosis (AK) and solar lentigines and shown to improve signs of photoaging.
      OBJECTIVES: To evaluate whether adapalene 0.3% gel is non-inferior to tretinoin
      0.05% cream as treatment for photoaged skin. MATERIALS & METHODS: An investigator
      blinded, parallel-group comparison study was conducted in Brazil. Subjects were
      randomised in a 1:1 ratio to receive, once daily, adapalene 0.3% gel or tretinoin
      0.05% cream. Subjects were evaluated at Weeks 1, 4, 8, 12, 16, 20 and 24, based
      on clinical signs of cutaneous photoaging, histopathological and digital
      morphometric findings, as well as safety and tolerability. RESULTS: A comparison
      of clinical efficacy showed that both treatments did not differ significantly
      regarding clinical evaluation of the following criteria: global cutaneous
      photoaging, periorbital wrinkles, ephelides/melanosis, forehead wrinkles, and AK.
      CONCLUSION: Adapalene 0.3% gel showed non-inferior efficacy to tretinoin 0.05%
      cream as treatment for photoaged skin, with a similar safety profile. Adapalene
      0.3% gel may therefore be considered a safe and effective option for the
      treatment of mild or moderate photoaging.

PMID- 30105994
TI  - Local desensitization and progression of multiple fixed drug eruption.

PMID- 30105993
TI  - Retrospective analysis of the application of fumaric acid esters in 13 patients
      with alopecia areata.

PMID- 30105995
TI  - Impetigo herpetiformis with IL-36RN mutation successfully treated with
      secukinumab.

PMID- 30105996
TI  - Fibro-osseous pseudotumour of the digit associated with prominent bone formation:
      time course of the tumour and clinicopathology.

PMID- 30105998
TI  - Anti-MDA5 antibody-positive bullous dermatomyositis with thyroid carcinoma.

PMID- 30105997
TI  - Generalized pustular psoriasis as an unusual cause of acquired haemophilia A.

PMID- 30105999
TI  - What's new this month?

PMID- 30106000
TI  - Cutaneous Drug Reactions: typical and atypical cases of a distinctive drug
      reaction.

PMID- 30106001
TI  - Dermpath & Clinic: Juvenile xanthogranuloma.

PMID- 30106002
TI  - sQuiz your knowledge: Greenish macules and papules on the feet.

PMID- 30106003
TI  - Fecal pancreatic elastase-1 and erythrocyte magnesium levels in diabetes type 1
      and type 2.
AB  - : In both types of diabetes mellitus (DM), type 1 and type 2 (T1DM and T2DM),
      there are both endocrine and exocrine dysfunctions of the pancreas (PED), as well
      as disturbances in serum magnesium levels. The aim of this study was to examine
      the frequency of PED according to the level of fecal elastase-1 (FE-1) in
      patients with T1DM and T2DM, determining the correlation of the level of FE-1
      with certain anthropometric parameters, certain indicators of metabolic
      regulation of diabetes, and certain nutritive markers of PED. MATERIALS AND
      METHODS: In the examinees, (56 with T1DM (F = 35 and M = 21), 62 with T2DM (F =
      30 and M = 32), and 40 in the control group (F = 19 and M = 21)), we examined
      anthropometric parameters, and using standard biochemical methods, we measured
      the level of FE-1, magnesium concentration in blood and erythrocytes, and
      selected blood parameters. RESULTS: FE-1 concentration < 200 MUg/g was present in
      14.2% of the examinees with T1DM, 20.9% with T2DM, and 2.5% in the control group.
      In all examinees with DM, there was a statistically significant correlation (P <
      0.05) between the level of FE-1 and Mg concentration in the erythrocytes (R =
      0.40). CONCLUSIONS: Prevalence of pancreatic exocrine insufficiency (PEI),
      according to the level of FE-1, is significantly higher in patients with DM than
      in the control group, while it is a bit higher in patients with T2DM than the
      ones with T1DM. In both types of DM, Mg concentration in erythrocytes is in a
      significant correlation with the level of FE-1.

PMID- 30106004
TI  - Uniaxial and hydrostatic pressure effects in alpha-RuCl3 single crystals via
      thermal-expansion measurements.
AB  - We present high-resolution thermal-expansion and specific-heat measurements of
      single crystalline alpha-RuCl3. An extremely hysteretic structural transition
      expanding over 100 K is observed by thermal-expansion along both crystallographic
      axes, which we attribute to a change of stacking sequence of the RuCl3 layers.
      Three magnetic transitions are observed, which we link to the different stacking
      sequences. Using our data and thermodynamic relations, we derive the uniaxial and
      hydrostatic pressure derivatives of all three magnetic transitions. Our results
      demonstrate that magnetic order of the major transition at  ~7 K should be
      totally suppressed by very moderate pressures of 0.3 GPa. Finally, we discuss why
      our results differ from recent hydrostatic pressure measurements and suggest a
      possible route to reaching the spin-liquid state in alpha-RuCl3.

PMID- 30106005
TI  - Self-powered single semiconductor nanowire photodetector.
AB  - Self-powered photodetectors have been fabricated from a single germanium nanowire
      (NW) in the metal-semiconductor-metal (MSM) device configuration. The self
      powered devices show a high photoresponse (responsivity ~ 103-105 A W-1) in the
      wavelength range 300-1100 nm. It has been established from I-V characteristics
      that asymmetry exists in the Schottky barrier height (SBH) at the two MS
      contacts. We have used simulation to establish that the asymmetric SBH at the
      metal contacts in an MSM device is a major cause for the 'built-in' axial field
      that leads to separation of a light generated electron-hole pair in the absence
      of an applied bias. Thus, even in the absence of external bias, the
      photogenerated carriers can be separated, which then diffuse to the appropriate
      electrodes driven by the 'built-in' axial field. We also point out the physical
      origins that can lead to unequal barrier heights in seemingly identical NW/metal
      junctions in a MSM device.

PMID- 30106006
TI  - Magnetic and energetic properties of transition metal doped alumina.
AB  - A doped non-diamagnetic alumina (Al2O3) would enable the usage of cutting edge
      technology, such as magnetoforming, to create advanced systems that take
      advantage of the high chemical and physical resilience of alumina. This study
      elucidates the magnetic properties of Cr, Fe, Ni, and Cu doped alpha- and theta
      alumina. Density functional theory was used to predict the structural,
      electronic, and magnetic properties of doped alumina, as well as its stability.
      The results indicate that the dopant species and coordination environment are the
      most important factors in determining the spin density distribution and net
      magnetic moment, which will strongly direct the ability of the doped alumina to
      couple with an external field. Similar coordination environments in different
      phases produce similar spin densities and magnetic moments, indicating that the
      results presented in this work may be generalizable to the other five or more
      phases of alumina not studied here.

PMID- 30106007
TI  - Ground-state structures, physical properties and phase diagram of carbon-rich
      nitride C5N.
AB  - Using the ab initio evolutionary algorithm, four thermodynamically stable C5N
      phases ([Formula: see text], [Formula: see text]-1, [Formula: see text]-2 and
      C2/m) are uncovered. The structures of the [Formula: see text], [Formula: see
      text]-1 and [Formula: see text]-2 phases possess layered features. The dense C2/m
      phase with 3D strong covalent bond network is calculated to be superhard with
      hardness of 75.4 and 83.9 GPa by Chen and Gao models. The electronic properties
      of the C5N is diverse including conductor ([Formula: see text]), indirect
      semiconductor ([Formula: see text]-1 and [Formula: see text]-2) and direct
      semiconductor (C2/m). Pressure-induced phase transition sequences and critical
      pressure points are calculated to be [Formula: see text]  ->  [Formula: see text]
      1  ->  [Formula: see text]-2 at 2.7 and 34 GPa, respectively. Though the C2/m
      phase is metastable at zero temperature, our established pressure-temperature
      phase diagram of C5N shows that the C2/m becomes stable under high temperatures
      and pressures. The pressure-temperature phase diagram will give theoretical
      guidance for further experimental synthesis of different C5N phases.

PMID- 30106008
TI  - Developing an efficient phase-matched attenuation correction method for quiescent
      period PET in abdominal PET/MRI.
AB  - Respiratory motion causes misalignments between positron emission tomography
      (PET) and magnetic resonance (MR)-derived attenuation maps (u-maps) in addition
      to artifacts on both PET and MR images in simultaneous PET/MRI for organs such as
      liver that can experience motion of several centimeters. To address this problem,
      we developed an efficient MR-based attenuation correction (MRAC) method to
      generate phase-matched u-maps for quiescent period PET (PETQ) in abdominal
      PET/MRI. MRAC data was acquired with CIRcular Cartesian UnderSampling (CIRCUS)
      sampling during 100 s in free-breathing as an accelerated data acquisition
      strategy for phase-matched MRAC (MRACPM-CIRCUS). For comparison, MRAC data with
      raster (Default) k-space sampling was also acquired during 100 s in free
      breathing (MRACPM-Default), and used to evaluate MRACPM-CIRCUS as well as un
      matched MRAC (MRACUM) that was un-gated. We purposefully oversampled the MRACPM
      data to ensure we had enough information to capture all respiratory phases to
      make this comparison as robust as possible. The proposed MRACPM-CIRCUS was
      evaluated in 17 patients with 68Ga-DOTA-TOC PET/MRI exams, suspected of having
      neuroendocrine tumors or liver metastases. Effects of CIRCUS sampling for
      accelerating a data acquisition were evaluated by simulating the data acquisition
      time retrospectively in increments of 5 s. Effects of MRACPM-CIRCUS on PETQ were
      evaluated using uptake differences in the liver lesions (n  =  35), compared to
      PETQ with MRACPM-Default and MRACUM. A Wilcoxon signed-rank test was performed to
      compare lesion uptakes between the MRAC methods. MRACPM-CIRCUS showed higher
      image quality compared to MRACPM-Default for the same acquisition times,
      demonstrating that a data acquisition time of 30 s was reasonable to achieve
      phase-matched u-maps. Lesion update differences between MRACPM-CIRCUS (30 s)
      versus MRACPM-Default (reference, 100 s) were 0.1%  +/-  1.4% (range of  -2.7% to
      3.2%) and not significant (P  >  .05); while, the differences between MRACUM
      versus MRACPM-Default were 0.6%  +/-  11.4% with a large variation (range of  
      37% to 20%) and significant (P  <  .05). In conclusion, we demonstrated that a
      data acquisition of 30 s achieved phase-matched u-maps when using specialized
      CIRCUS data sampling and phase-matched u-maps improved PETQ quantification
      significantly.

PMID- 30106010
TI  - Luminescent, low-toxic and stable gradient-alloyed Fe:ZnSe(S)@ZnSe(S) core:shell
      quantum dots as a sensitive fluorescent sensor for lead ions.
AB  - In this paper, an aqueous-based approach is introduced for facile, fast, and
      green synthesis of gradient-alloyed Fe-doped ZnSe(S)@ZnSe(S) core:shell quantum
      dots (QDs) with intense and stable emission. Co-utilization of co-nucleation and
      growth doping strategies, along with systematic optimization of emission
      intensity, provide a well-controllable/general method to achieve internally doped
      QDs (d-dots) with intense emission. Results indicate that the alloyed
      ZnSe(S)@ZnSe(S) core:shell QDs have a gradient structure that consists of a Se
      rich core and a S-rich shell. This gradient structure cannot only passivate the
      core d-dots by means of the wider band gap S-rich shell, but also minimizes the
      lattice mismatch between alloyed core-shell structures. Using this novel strategy
      and utilizing the wider band gap S-rich shell can obviously increase the cyan
      emission intensity and also drastically improve the emission stability against
      chemical and optical corrosion. Furthermore, the cytotoxicity experiments
      indicate that the obtained d-dots are nontoxic nanomaterials, and thus they can
      be considered as a promising alternative to conventional Cd-based QDs for
      fluorescent probes in biological fields. Finally, it is demonstrated that the
      present low-toxicity and gradient-alloyed core:shell d-dots can be used as
      sensitive chemical detectors for Pb2+ ions with excellent selectivity, small
      detection limit, and rapid response time.

PMID- 30106009
TI  - Preparation and photocathodic protection property of ZnIn2S4/RGO/TiO2 composites
      for Q235 carbon steel under visible light.
AB  - For improving the photocathodic protection performance of TiO2 photoanode,
      ZnIn2S4/reduced graphene oxide (RGO)/TiO2 nanotubes (NTs) composite was
      synthesized by electrochemical anodizing combined with hydrothermal method. The
      photoelectrochemical and photocathodic protection properties of the
      ZnIn2S4/RGO/TiO2 composite were investigated in detail. Compared with pure TiO2
      NTs, the ZnIn2S4/RGO/TiO2 composite showed a significant improvement in
      photocathodic protection performances. The photogenerated open circuit potential
      drop of ZnIn2S4/RGO/TiO2 coupled with Q235 carbon steel in 3.5 wt% NaCl solution
      under visible light could reach 420 mV versus saturated calomel electrode, which
      was more than twice as much as that of pure TiO2. The photogenerated current
      density of ZnIn2S4/RGO/TiO2 could reach 5.6 mA cm-2, which was twice as much as
      that of pure TiO2. The appearance of the adsorbed oxygen (OA) enabled the
      ZnIn2S4/RGO/TiO2 to have better photo-carrier separation efficiency and better
      photogenerated cathodic protection than pure TiO2. The present work demonstrated
      ZnIn2S4/RGO/TiO2 could be a potential material for photoanodes because of its
      better visible-light response, higher electrical conductivity and smaller charge
      transfer resistance.

PMID- 30106012
TI  - The role of vasoepididymostomy for treatment of obstructive azoospermia in the
      era of in vitro fertilization: a systematic review and meta-analysis.
AB  - This study comprises a systematic review and meta-analysis of microsurgical
      vasoepididymostomy outcomes in epididymal obstructive azoospermia. A
      comprehensive literature search was performed using Medline, Embase, and the
      Cochrane library that included all studies related to microsurgical
      vasoepididymostomy. Keywords included "vasoepididymostomy," "epididymovasostomy,"
      "epididymal obstruction," and "epididymis obstruction." Event rate and risk ratio
      (RR) were estimated. Patency rate and pregnancy rate were investigated. The
      analysis comprised 1422 articles, including 42 observational studies with 2298
      enrolled patients performed from November 1978 to January 2017. The overall mean
      patency rate was 64.1% (95% confidence interval [CI]: 58.5%-69.3%; I2=83.0%), and
      the overall mean pregnancy rate was 31.1% (95% CI: 26.9%-35.7%; I2=73.0%). We
      performed a meta-analysis comparing the patency rate of bilateral microsurgical
      vasoepididymostomy and unilateral microsurgical vasoepididymostomy and found an
      RR of 1.38% (95% CI: 1.21%-1.57%; P < 0.00001). A comparison of the site of
      microsurgical vasoepididymostomy showed that caudal or corpus area was favorable
      for patency rate (RR = 1.17%; 95% CI: 1.01%-1.35%; P = 0.04). Patients with
      motile sperm in epididymal fluid exhibited an RR of 1.53% (95% CI: 1.11%-2.13%; P
      = 0.01) with respect to patency rate. Microsurgical vasoepididymostomy is an
      effective treatment for epididymal obstructive azoospermia that can improve male
      fertility. We find that performing microsurgical vasoepididymostomy bilaterally,
      anastomosing a larger caudal area, and containing motile sperm in epididymis
      fluid can potentially achieve a superior patency rate.

PMID- 30106011
TI  - Prior switching to a second-line nonsteroidal antiandrogen does not impact the
      therapeutic efficacy of abiraterone acetate in patients with metastatic
      castration-resistant prostate cancer: a real-world retrospective study.
AB  - Even in the era of novel targeted agents, switching to a second-line nonsteroidal
      antiandrogen (NSAA) is still widely used in treating metastatic castration
      resistant prostate cancer (mCRPC), especially in undeveloped countries. However,
      whether prior treatment with a second-line NSAA would impact the efficacy of
      abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC
      patients treated with Abi were analyzed. Among them, 21 were treated with a
      second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone,
      while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was
      compared between those with and without prior second-line NSAA using Kaplan-Meier
      curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi
      was similar between those with or without the prior switching treatment of
      flutamide, in terms of either prostate-specific antigen progression-free survival
      (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival
      (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6
      months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P =
      0.370). This is the first time that the impact of prior switching of treatment to
      a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed.
      Our data support that, use of prior sequential bicalutamide and flutamide does
      not seem to preclude response to abiraterone, although larger cohort studies and,
      ideally, a randomized controlled trial are needed. These findings will facilitate
      doctors' decision-making in the treatment of mCRPC patients, especially for those
      with previous experience of switching NSAA second-line treatments in the clinic.

PMID- 30106013
TI  - Benefits of orchidopexy on the fertility of adult men with bilateral
      cryptorchidism.

PMID- 30106014
TI  - Linear atrophoderma of Moulin: A rare entity.

PMID- 30106016
TI  - Verruciform xanthoma of the penis: A rare case with an unusual clinical
      morphology.

PMID- 30106015
TI  - Hypopigmented and acneiform lesions: An unusual initial presentation of adult
      onset multisystem Langerhans cell histiocytosis.

PMID- 30106018
TI  - Distal infection of the middle finger caused by Mycobacterium abscessus.

PMID- 30106020
TI  - Laparoscopic total extraperitoneal inguinal hernia repair is safe and feasible in
      patients with continuation of antithrombotics.
AB  - Aims: We aimed to evaluate the safety and feasibility of laparoscopic total
      extraperitoneal (TEP) inguinal hernia repair in patients with the continuation of
      their antithrombotic agents. Settings and Design: This was prospective cohort
      study. Materials and Methods: A total of 115 patients who underwent TEP inguinal
      hernia repair between January 2015 and September 2016 were included in the
      analysis. Seventeen patients continued their antithrombotics (antithrombotic
      group); the other 98 had not been on antithrombotics (control group). Statistical
      Analysis Used: The analysis was performed by using Mann-Whitney U-test, Chi
      square or Fisher's exact test. Results: The antithrombotic group had a greater
      mean age (65.9 +/- 8.0 vs. 57.7 +/- 13.6, P = 0.002) and higher prevalence of
      hypertension (64.7% vs. 33.7%, P = 0.015), cardiovascular diseases (64.7% vs.
      7.1%, P < 0.001), atrial fibrillation (23.5% vs. 0, P < 0.001), ischaemic heart
      disease (35.3% vs. 0, P < 0.001) and the American Society of Anaesthesiologists
      >=2 (94.1% vs. 81.6%, P = 0.005). The operation time for the antithrombotic group
      was longer than that of the control group (92.06 +/- 32.81 min vs. 72.33 +/-
      20.99 min, P = 0.015). None experienced conversion to open surgery in either
      group. There was no difference in the post-operative complications (29.4% vs.
      28.6%) and sero-haematoma formation (23.5% vs. 11.1%). The analgesic requirement,
      hospital stays (23.72 +/- 7.74 vs. 22.35 +/- 10.33 h) and the time for return to
      normal daily activity (3.56 +/- 1.74 vs. 3.63 +/- 1.90) were not statistically
      different between the two groups. None in either group experienced major
      cardiovascular events within 30 days. Conclusions: Laparoscopic TEP inguinal
      hernia repair can be safely performed in patients with the continuation of their
      antithrombotic agents in experienced hands.

PMID- 30106019
TI  - Seborrheic melanosis and dermoscopy: Lumping better than splitting.

PMID- 30106021
TI  - Exploring minimally invasive options: Laparoscopic transabdominal levator
      transection for low rectal cancers.
AB  - Extralevator abdominoperineal excision (ELAPE) of the rectum offers wider
      circumferential margin and decreased rate of intraoperative tumour perforation.
      However, the need to change the position of the patient in between abdominal and
      perineal stages of the procedure and extended perineal resection result in
      increased morbidity and operative time. Evolving technique of laparoscopic
      transabdominal controlled division of levator ani muscles under direct vision
      could address these issues while providing all benefits of ELAPE for patients
      with low rectal cancers.

PMID- 30106022
TI  - Laparoscopic resection of duodenal carcinoid: A feasible method: Single institute
      case series.
AB  - Background: Duodenal carcinoids (neuroendocrine tumour) are rare tumour, but
      recently, increase in incidence has been noted. Various techniques for excision
      of tumour have been described in literature, but very few case reports and case
      series have mentioned about laparoscopic management of carcinoid tumour. We
      describe a case series of seven cases of duodenal non-periampullary carcinoids
      which was managed by laparoscopic method. Aims: The aim of the study was to check
      feasibility of laparoscopic management of duodenal carcinoid and technique of
      surgery. Settings and Design: This study design was a case series and prospective
      data were retrospectively collected. Materials and Methods: A total of 7 patients
      were operated for carcinoid tumour of duodenum mainly involving first part by
      laparoscopic method from February 2016 to January 2017. All patients were
      followed up for minimum 1-year period and various pre-operative, intra-operative
      findings and post-operative outcome were noted. Results: Out of seven patients, 6
      patient were managed by laparoscopic duodenotomy and transduodenal excision
      whereas one patient required duodenectomy of first part. Mean operative time was
      99 min, mean intraoperative blood loss was 55.7, mean hospital stay was 99.7 and
      no recurrence in a 1-year follow-up. Conclusions: Laparoscopic excision of
      carcinoid tumour is safe, technically reproducible and feasible method.

PMID- 30106023
TI  - Laparoscopic donor hepatectomy: First experience from Indian sub-continent.
AB  - Liver transplantation is a ray of hope for thousands of patients with end-stage
      liver disease but is currently challenged by the scarcity of donor organs
      worldwide. Unlike kidney transplantation where minimally invasive donor organ
      procurement has almost become a norm, laparoscopic procurement of hemi-liver from
      a living donor is still in the infancy of development, at least in the Indian sub
      continent. Minimally invasive surgery has made its way into different procedures
      of hepatobiliary and pancreatic surgery, but only a few centres in the world are
      performing pure laparoscopic donor hepatectomy. We report two cases of total
      laparoscopic donor hepatectomy, and to the best of our knowledge, this is the
      first report from Indian sub-continent.

PMID- 30106024
TI  - Laparoscopic hand-assisted liver resection for tumours in the left lateral
      section.
AB  - Context: The role of the laparoscopic left lateral sectionectomy (LLLS) is
      debatable, and Level-1 data are lacking. Aims: The aim of the study is to
      evaluate the feasibility and safety of this approach. Settings and Design: This
      was a retrospective study. Subjects and Methods: From 2007 to 2014, patients
      undergoing LLLS were identified from two institutions. Statistical Analysis Used:
      Continuous variables were compared between groups with Student's t-test or Mann
      Whitney test, as appropriate by type of distribution. Categorical variables were
      compared with Chi-square or Fisher's exact test, depending on the number of
      observations. Results: Thirty-eight patients were included in the study. The mean
      age was 63.5 + 13 years (range, 31-89), and the mean number of tumours was 1.7 +
      1.5. Eleven (29%) patients underwent LLS combined with an additional liver
      resection (combined resections group). The mean duration of the operation and the
      mean estimated blood loss were significantly decreased in the LLS group compared
      to the combined resection group (101 + 71 min vs. 208 + 98 min and 216 + 217 ml
      vs. 450 + 223 ml; P < 0.05 for both, respectively). The major complications rate
      was 8% and no mortality occurred. Conclusions: In a subset of carefully selected
      cases, LLLS may provide the benefits of laparoscopy. This does not appear to
      compromise perioperative morbidity rates. We believe that this approach may serve
      as a training platform for surgical trainees.

PMID- 30106026
TI  - Comparative study of laparoscopic radical gastrectomy and open radical
      gastrectomy.
AB  - Introduction: At present, the main treatment of gastric cancer is surgical
      resection combined with radiotherapy and chemotherapy, the most important part of
      which is radical gastrectomy. Laparoscopic radical gastrectomy for advanced
      gastric cancer is difficult to operate, and whether it can achieve the same
      curative effect with the laparotomy is still controversial. Materials and
      Methods: This study retrospectively analysed the clinical data of 269 gastric
      cancer patients surgically treated by our medical team from May 2011 to December
      2015 for comparative analysis of the clinical efficacy of laparoscopic-assisted
      radical gastrectomy and traditional open radical gastrectomy. Results: The
      laparoscopic surgery group had longer duration of surgery, less intra-operative
      blood loss, shorter post-operative exhaust time, shorter post-operative hospital
      stay and shorter timing of drain removal. . The average number of harvested lymph
      nodes in the laparoscopic surgery group was 22.9 +/- 9.5 per case. And in the
      laparotomy group the average number was 23.3 +/- 9.9 per case. The difference had
      no statistical significance. With the increase of the number of laparoscopic
      surgical procedures, the amount of intra-operative blood loss gradually
      decreases, and the duration of surgery is gradually reduced. Conclusion:
      Laparoscopic radical gastrectomy is superior to open surgery in the aspects of
      intra-operative blood loss, post-operative exhaust time, post-operative hospital
      stay and timing of drain removal. With the number of laparoscopic radical
      gastrectomy cases increased, the duration of surgery is shortened and the amount
      of intra-operative blood loss will decrease.

PMID- 30106027
TI  - 'Colleaguography' in place of cholangiography, to prevent bile duct injury during
      laparoscopic cholecystectomy.
AB  - Bile duct injury (BDI) is not uncommon during laparoscopic cholecystectomy (LC).
      Intra-operative cholangiography (IOC) has been recommended to reduce the risk of
      BDI during LC. Facilities for IOC are, however, scarcely available in India. The
      author suggests 'in vicinity colleaguography' (IVC) - opinion of a surgical
      colleague in vicinity - as an easy alternative to IOC.

PMID- 30106028
TI  - The importance of long-term postoperative follow-up, including low threshold for
      endoscopic examination of the remnant stomach after Roux-en-Y gastric bypass.

PMID- 30106025
TI  - Systematic review on citation classics in minimally invasive gastrointestinal
      surgery.
AB  - Background: The impact an article has on a specific field is manifested by its
      number of citations. The aim of this systematic review was to perform a citation
      analysis and identify the 100 most-cited articles in the field of minimally
      invasive (MI) gastrointestinal (GI) surgery. Methods: The Institute for
      Scientific Information Web of Knowledge (1945-2017) was utilised to identify the
      top 100 most-cited articles in the field of MI GI surgery, using 19 distinct
      keywords. The data extracted were number of citations, time of publication,
      research topic, level of evidence, authorship and country of origin. Results: Of
      the 100 most-cited articles, the number of citations ranged from 3331 to 317
      citations. Most publications reported on bariatric surgery (n = 36), followed by
      oncology (n = 26) and hepatobiliary surgery (n = 15). The studies were published
      in 26 different journals with the top three journals being Annals of Surgery (n =
      30), New England Journal of Medicine (n = 10) and Obesity Surgery (n = 9). The
      studies were conducted in 17 different countries led by the USA (n = 51), the UK
      (n = 9) and France (n = 6). Articles were published on all levels of evidence:
      level I (n = 20), Level II (n = 29), Level III (n = 8), Level IV (n = 29) and
      Level V (n = 14). Conclusion: The study revealed citation classics in the field
      of MI surgery. Interestingly, a high level of evidence was not significantly
      associated with an increased citation number.

PMID- 30106029
TI  - Laparoscopic hepatectomy for patients who received enterostomy.
AB  - Background: Laparoscopic hepatectomy is more conducive to the rapid
      rehabilitation of patients after surgery compared with open hepatectomy. However,
      there have been no reports on performing laparoscopic resection for liver
      metastases in enterostomy patients. Materials: From December 2016 to April 2017,
      the Liver Surgery Department of the Peking Union Medical College Hospital
      received three patients who had focal liver lesions after colorectal cancer
      surgery and enterostomy. We performed laparoscopic hepatectomy for these three
      patients and reviewed relevant literature. Results: All of these three patients'
      post-operative recovery was good. We found three different positions of the
      stomas and the corresponding abdominal adhesions in these three patients. We also
      summarised several possible related surgical techniques. Conclusion: For patients
      with colorectal cancer and enterostomy after an operation, implementation of
      laparoscopic hepatectomy is feasible. Further research is still required for a
      more comprehensive assessment of this surgical approach.

PMID- 30106030
TI  - Evaluation of 5-year results of laparoscopic transhiatal oesophagectomy as a
      single-centre experience.
AB  - Introduction: Minimal Invasive Surgery of oesophageal cancers is gaining
      popularity. We have published our Thoracoscopic Esophagectomy results. The
      present study focuses on our expertise of TransHiatal Esophagectomy. Materials
      and Methods: 287 patients underwent Esophagectomies for Cancer of Esophagus at
      Galaxy Care Laparoscopy Institute from January 2010 to December 2014 after
      thorough assesment. Out of these, 81 patients underwent laparoscopic trans hiatal
      esophagectomies. Their charts were reviewed retrospectively for intraoperative
      and postoperative results. The median follow up was 28 months. Results: Out of 81
      patients,76 patients had R0 resection and 5 had R1. The average lymphnode yield
      was 20,average survival was 28months. 3 patients had local recurrence,18 had
      regional recurrence and 30 had distant recurrence. Average operating time was 140
      min,mean blood loss was 80 ml. Average Post-operative ICU stay was 1 day and
      hospital stay 7 days. Conclusion: Classic THE has limitations which can be
      overcome by the use of laparoscopic techniques. Laparoscopic approach for THE has
      better magnified vision facilitating better clearance under vision. Hence we
      recommend laparoscopic technique for THE to minimize morbidity and improve
      oncologic results.

PMID- 30106031
TI  - Structural brain volume differences between cognitively intact ApoE4 carriers and
      non-carriers across the lifespan.
AB  - Apolipoprotein E4 (ApoE4) is a prominent genetic risk factor for Alzheimer's
      disease. The purpose of this review is to explore differences in structural brain
      volume detected by magnetic resonance imaging between cognitively intact ApoE4
      carriers and non-carriers across the lifespan (i.e., older adults, middle-aged
      adults, young adults, children and adolescents, and neonates). Consistent
      findings are found throughout various developmental stages. This area of research
      may elucidate the mechanisms by which ApoE4 influences risk of developing
      Alzheimer's disease. It could also inform potential treatment strategies and
      interventions for carriers of the ApoE4 allele.

PMID- 30106033
TI  - Neuroplasticity, limbic neuroblastosis and neuro-regenerative disorders.
AB  - The brain is a dynamic organ of the biological renaissance due to the existence
      of neuroplasticity. Adult neurogenesis abides by every aspect of neuroplasticity
      in the intact brain and contributes to neural regeneration in response to brain
      diseases and injury. The occurrence of adult neurogenesis has unequivocally been
      witnessed in human subjects, experimental and wildlife research including
      rodents, bats and cetaceans. Adult neurogenesis is a complex cellular process, in
      which generation of neuroblasts namely, neuroblastosis appears to be an integral
      process that occur in the limbic system and basal ganglia in addition to the
      canonical neurogenic niches. Neuroblastosis can be regulated by various factors
      and contributes to different functions of the brain. The characteristics and fate
      of neuroblasts have been found to be different among mammals regardless of their
      cognitive functions. Recently, regulation of neuroblastosis has been proposed for
      the sensorimotor interface and regenerative neuroplasticity of the adult brain.
      Hence, the understanding of adult neurogenesis at the functional level of
      neuroblasts requires a great scientific attention. Therefore, this mini-review
      provides a glimpse into the conceptual development of neuroplasticity, discusses
      the possible role of different types of neuroblasts and signifies
      neuroregenerative failure as a potential cause of dementia.

PMID- 30106032
TI  - Roles of Eph/ephrin bidirectional signaling during injury and recovery of the
      central nervous system.
AB  - Multiple cellular components, including neuronal, glial and endothelial cells,
      are involved in the sophisticated pathological processes following central
      nervous system injury. The pathological process cannot reduce damage or improve
      functional recovery by merely targeting the molecular mechanisms of neuronal cell
      death after central nerve system injuries. Eph receptors and ephrin ligands have
      drawn wide attention since the discovery of their extensive distribution and
      unique bidirectional signaling between astrocytes and neurons. The roles of
      Eph/ephrin bidirectional signaling in the developmental processes have been
      reported in previous research. Recent observations suggest that Eph/ephrin
      bidirectional signaling continues to be expressed in most regions and cell types
      in the adult central nervous system, playing diverse roles. The Eph/ephrin
      complex mediates neurogenesis and angiogenesis, promotes glial scar formation,
      regulates endocrine levels, inhibits myelin formation and aggravates inflammation
      and nerve pain caused by injury. The interaction between Eph and ephrin is also
      considered to be the key to angiogenesis. This review focuses on the roles of
      Eph/ephrin bidirectional signaling in the repair of central nervous system
      injuries.

PMID- 30106035
TI  - Targeting the noradrenergic system for anti-inflammatory and neuroprotective
      effects: implications for Parkinson's disease.
AB  - Degeneration of the locus coeruleus noradrenergic system is thought to play a key
      role in the pathogenesis of Parkinson's disease (PD), whereas pharmacological
      approaches to increase noradrenaline bioavailability may provide neuroprotection.
      Noradrenaline inhibits microglial activation and suppresses pro-inflammatory
      mediator production (e.g., tumor necrosis factor-alpha, interleukin-1beta &
      inducible nitric oxide synthase activity), thus limiting the cytotoxicity of
      midbrain dopaminergic neurons in response to an inflammatory stimulus.
      Neighbouring astrocyte populations promote a neurotrophic environment in response
      to beta2-adrenoceptor (beta2-AR) stimulation via the production of growth factors
      (e.g., brain derived neurotrophic factor, cerebral dopamine neurotrophic factor &
      glial cell derived neurotrophic factor which have shown promising neuroprotective
      and neuro-restorative effects in the nigrostriatal dopaminergic system. More
      recent findings have demonstrated a role for the beta2-AR in down-regulating
      expression levels of the human alpha-synuclein gene SNCA and relative alpha
      synuclein protein abundance. Given that alpha-synuclein is a major protein
      constituent of Lewy body pathology, a hallmark neuropathological feature in
      Parkinson's disease, these findings could open up new avenues for pharmacological
      intervention strategies aimed at alleviating the burden of alpha
      synucleinopathies in the Parkinsonian brain. In essence, the literature reviewed
      herein supports our hypothesis of a tripartite neuroprotective role for
      noradrenaline in combating PD-related neuropathology and motor dysfunction via
      (1) inhibiting nigral microglial activation & pro-inflammatory mediator
      production, (2) promoting the synthesis of neurotrophic factors from midbrain
      astrocytes and (3) downregulating alpha-synuclein gene expression and protein
      abundance in a beta2-AR-dependent manner. Thus, taken together, either
      pharmacologically enhancing extra-synaptic noradrenaline bioavailability or
      targeting glial beta2-ARs directly makes itself as a promising treatment option
      aimed at slowing/halting PD progression.

PMID- 30106034
TI  - A tissue-engineered rostral migratory stream for directed neuronal replacement.
AB  - New neurons are integrated into the circuitry of the olfactory bulb throughout
      the lifespan in the mammalian brain-including in humans. These new neurons are
      born in the subventricular zone and subsequently mature as they are guided over
      long distances via the rostral migratory stream through mechanisms we are only
      just beginning to understand. Regeneration after brain injury is very limited,
      and although some neuroblasts from the rostral migratory stream will leave the
      path and migrate toward cortical lesion sites, this neuronal replacement is
      generally not sustained and therefore does not provide enough new neurons to
      alleviate functional deficits. Using newly discovered microtissue engineering
      techniques, we have built the first self-contained, implantable constructs that
      mimic the architecture and function of the rostral migratory stream. This
      engineered microtissue emulates the dense cord-like bundles of astrocytic somata
      and processes that are the hallmark anatomical feature of the glial tube. As
      such, our living microtissue-engineered rostral migratory stream can serve as an
      in vitro test bed for unlocking the secrets of neuroblast migration and
      maturation, and may potentially serve as a living transplantable construct
      derived from a patient's own cells that can redirect their own neuroblasts into
      lesion sites for sustained neuronal replacement following brain injury or
      neurodegenerative disease. In this paper, we summarize the development of
      fabrication methods for this microtissue-engineered rostral migratory stream and
      provide proof-of-principle evidence that it promotes and directs migration of
      immature neurons.

PMID- 30106036
TI  - Targeting the mitochondrial permeability transition pore in traumatic central
      nervous system injury.
AB  - The mitochondrion serves many functions in the central nervous system (CNS) and
      other organs beyond the well-recognized role of adenosine triphosphate (ATP)
      production. This includes calcium-dependent cell signaling, regulation of gene
      expression, synthesis and release of cytotoxic reactive oxygen species, and the
      release of cytochrome c and other apoptotic cell death factors. Traumatic injury
      to the CNS results in a rapid and, in some cases, sustained loss of mitochondrial
      function. One consequence of compromised mitochondrial function is induction of
      the mitochondrial permeability transition (mPT) state due to formation of the
      cyclosporine A sensitive permeability transition pore (mPTP). In this mini
      review, we summarize evidence supporting the involvement of the mPTP as a
      mediator of mitochondrial and cellular demise following CNS traumatic injury and
      discuss the beneficial effects and limitations of the current ex-perimental
      strategies targeting the mPTP.

PMID- 30106037
TI  - Current surgical treatments for Parkinson's disease and potential therapeutic
      targets.
AB  - Currently, the most common surgical treatment for Parkinson's disease is deep
      brain stimulation (DBS). This treatment strategy is typically reserved for
      bradykinesia, rigidity and tremor in patients who no longer respond to medication
      in a predictable manner or who suffer medication-induced dyskinesias. In addition
      to DBS, ablative procedures like radiofrequency, radiosurgery and focused
      ultrasound are also utilized for select tremor symptoms. In this review, we
      discuss evolving surgical techniques, targets, and emerging technology. In
      addition, we evaluate potential paradigm shifts in treatment, including gene
      therapy, immunotherapy and cell transplantation. While these new techniques and
      treatment options are still in their infancy, advances in Parkinson's disease
      treatment are rapidly expanding.

PMID- 30106038
TI  - Amnion epithelial cells - a novel therapy for ischemic stroke?
AB  - Stroke is a leading cause of death and disability and new therapies are
      desperately needed. Given the complex nature of ischemic brain injury, it has
      been postulated that cell-based therapies may be useful. However, cell resources,
      invasive extraction procedures, immunological rejection, tumorigenesis and
      ethical challenges make it unlikely that many stem cell types could serve as a
      practical source for therapy. By contrast, these issues do not pertain to human
      amnion epithelial cells (hAECs), which are placenta-derived stem cells. We
      recently assessed the effects of systemically delivered hAECs on stroke outcome
      using four animal models of stroke. We demonstrated that when injected
      intravenously after ischemia onset, hAECs migrate preferentially to the spleen
      and injured brain to limit apoptosis and inflammation, and attenuate early brain
      infiltration of immune cells, progression of infarction and systemic
      immunosuppression and to ultimately ameliorate functional deficits. When
      administration of hAECs is delayed by 1-3 days post-stroke, long-term functional
      recovery can still be enhanced in young and aged mice of either sex. Moreover,
      our proof-of-principle findings suggest that hAECs are effective at limiting post
      stroke infarct development in non-human primates. Overall, the results suggest
      that hAECs could be a viable clinical stroke therapy.

PMID- 30106039
TI  - Cell-based therapies for neural replacement strategies in stroke-related
      neurodegeneration: neurophysiological insights into stem progenitor cell
      neurogenesis within a host environment.

PMID- 30106040
TI  - Stem cell therapy for retinal ganglion cell degeneration.

PMID- 30106041
TI  - Exercise and hippocampal neurogenesis: a dogma re-examined and lessons learned.

PMID- 30106042
TI  - Bioelemental patterns in the cerebrospinal fluid as potential biomarkers for
      neurodegenerative disorders.

PMID- 30106044
TI  - Cholinergic receptor, nicotinic, alpha 7 as a target molecule of Arctic mutant
      amyloid beta.

PMID- 30106043
TI  - Perspectives on "the biology of spinal cord regeneration success and failure".

PMID- 30106045
TI  - Gamma-aminobutyric acid A receptors in Alzheimer's disease: highly localized
      remodeling of a complex and diverse signaling pathway.

PMID- 30106046
TI  - Factors contributing to clinical picture and progression of Huntington's disease.

PMID- 30106047
TI  - Drug repurposing for neuroregeneration in multiple sclerosis.

PMID- 30106048
TI  - Advanced glycation end products induce neural tube defects through elevating
      oxidative stress in mice.
AB  - Our previous study showed an association between advanced glycation end products
      (AGEs) and neural tube defects (NTDs). To understand the molecular mechanisms
      underlying the effect of AGEs on neural tube development, C57BL/6 female mice
      were fed for 4 weeks with commercial food containing 3% advanced glycation end
      product bovine serum albumin (AGE-BSA) or 3% bovine serum albumin (BSA) as a
      control. After mating mice, oxidative stress markers including malondialdehyde
      and H2O2 were measured at embryonic day 7.5 (E7.5) of gestation, and the level of
      intracellular reactive oxygen species (ROS) in embryonic cells was determined at
      E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was
      used to determine the effect of embryonic protein administration on the N
      (carboxymethyl) lysine reactivity of acid and carboxyethyl lysine antibodies at
      E10.5. The results showed a remarkable increase in the incidence of NTDs at E10.5
      in embryos of mice fed with AGE-BSA (no hyperglycemia) compared with control
      mice. Moreover, embryonic protein administration resulted in a noticeable
      increase in the reactivity of N-(carboxymethyl) lysine and N(epsilon)
      (carboxyethyl) lysine antibodies. Malondialdehyde and H2O2 levels in embryonic
      cells were increased at E7.5, followed by increased intracellular ROS levels at
      E8.5. Vitamin E supplementation could partially recover these phenomena.
      Collectively, these results suggest that AGE-BSA could induce NTDs in the absence
      of hyperglycemia by an underlying mechanism that is at least partially associated
      with its capacity to increase embryonic oxidative stress levels.

PMID- 30106050
TI  - Effects of repetitive transcranial magnetic stimulation on cognitive function and
      cholinergic activity in the rat hippocampus after vascular dementia.
AB  - Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive treatment
      that can enhance the recovery of neurological function after stroke. Whether it
      can similarly promote the recovery of cognitive function after vascular dementia
      remains unknown. In this study, a rat model for vascular dementia was established
      by the two-vessel occlusion method. Two days after injury, 30 pulses of rTMS were
      administered to each cerebral hemisphere at a frequency of 0.5 Hz and a magnetic
      field intensity of 1.33 T. The Morris water maze test was used to evaluate
      learning and memory function. The Karnovsky-Roots method was performed to
      determine the density of cholinergic neurons in the hippocampal CA1 region.
      Immunohistochemical staining was used to determine the number of brain-derived
      neurotrophic factor (BDNF)-immunoreactive cells in the hippocampal CA1 region.
      rTMS treatment for 30 days significantly improved learning and memory function,
      increased acetylcholinesterase and choline acetyltransferase activity, increased
      the density of cholinergic neurons, and increased the number of BDNF
      immunoreactive cells. These results indicate that rTMS can ameliorate learning
      and memory deficiencies in rats with vascular dementia. The mechanism through
      which this occurs might be related to the promotion of BDNF expression and
      subsequent restoration of cholinergic system activity in hippocampal CA1 region.

PMID- 30106051
TI  - Acupuncture improves dendritic structure and spatial learning and memory ability
      of Alzheimer's disease mice.
AB  - Acupuncture can improve the cognitive state of Alzheimer's disease, but its
      mechanism is not clear. Dendritic atrophy and synaptic loss in Alzheimer's
      disease brain are positively correlated with cognitive damage. Therefore, we
      speculated that the effect of acupuncture on improving cognitive function may be
      associated with reduced dendritic damage in the brain. Acupuncture at Qihai
      (CV6), Zhongwan (CV12), Danzhong (CV17), bilateral Zusanli (ST36), and bilateral
      Xuehai (SP10) acupoints was performed once a day (1-day rest after 6-day
      treatment) for 14 consecutive days. Senescence-accelerated mouse prone 8 (SAMP8)
      mice without acupuncture and senescence-accelerated mouse resistant 1 (SAMR1)
      mice were used as normal controls. After 14 days of treatment, spatial learning
      and memory ability of mice was assessed in each group using the Morris water
      maze. Dendritic changes of pyramidal cells in the hippocampal CA1 region were
      analyzed by quantitative Golgi staining. Our results showed that acupuncture
      shortened escape latency and lengthened retention time of the former platform
      quadrant in SAMP8 mice. Further, SAMP8 mice exhibited a significant increase in
      the number of apical and basal dendritic branches and total length of apical and
      basal dendrites after acupuncture. These results suggest that acupuncture
      improves spatial learning and memory ability of middle-aged SAMP8 mice by
      ameliorating dendritic structure.

PMID- 30106049
TI  - Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant
      alpha-synuclein.
AB  - Genistein, a potent antioxidant compound, protects dopaminergic neurons in a
      mouse model of Parkinson's disease. However, the mechanism underlying this action
      remains unknown. This study investigated human SH-SY5Y cells overexpressing the
      A53T mutant of alpha-synuclein. Four groups of cells were assayed: a control
      group (without any treatment), a genistein group (incubated with 20 MUM
      genistein), a rotenone group (treated with 50 MUM rotenone), and a rotenone +
      genistein group (incubated with 20 MUM genistein and then treated with 50 MUM
      rotenone). A lactate dehydrogenase release test confirmed the protective effect
      of genistein, and genistein remarkably reversed mitochondrial oxidative injury
      caused by rotenone. Western blot assays showed that BCL-2 and Beclin 1 levels
      were markedly higher in the genistein group than in the rotenone group. Terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling revealed that
      genistein inhibited rotenone-induced apoptosis in SH-SY5Y cells. Compared with
      the control group, the expression of NFE2L2 and HMOX1 was significantly increased
      in the genistein + rotenone group. However, after treatment with estrogen
      receptor and NFE2L2 channel blockers (ICI-182780 and ML385, respectively),
      genistein could not elevate NFE2L2 and HMOX1 expression. ICI-182780 effectively
      prevented genistein-mediated phosphorylation of NFE2L2 and remarkably suppressed
      phosphorylation of AKT, a protein downstream of the estrogen receptor. These
      findings confirm that genistein has neuroprotective effects in a cell model of
      Parkinson's disease. Genistein can reduce oxidative stress damage and cell
      apoptosis by activating estrogen receptors and NFE2L2 channels.

PMID- 30106052
TI  - Scutellarin protects oxygen/glucose-deprived astrocytes and reduces focal
      cerebral ischemic injury.
AB  - Scutellarin, a bioactive flavone isolated from Scutellaria baicalensis, has anti
      inflammatory, anti-neurotoxic, anti-apoptotic and anti-oxidative effects and has
      been used to treat cardiovascular and cerebrovascular diseases in China. However,
      the mechanisms by which scutellarin mediates neuroprotection in cerebral ischemia
      remain unclear. The interaction between scutellarin and nicotinamide adenine
      dinucleotide phosphate oxidase 2 (NOX2) was assessed by molecular docking study,
      which showed that scutellarin selectively binds to NOX2 with high affinity.
      Cultures of primary astrocytes isolated from the cerebral cortex of neonatal
      Sprague-Dawley rats were pretreated with 2, 10 or 50 MUM scutellarin for 30
      minutes. The astrocytes were then subjected to oxygen/glucose deprivation by
      incubation for 2 hours in glucose-free Dulbecco's modified Eagle's medium in a
      95% N2/5% CO2 incubator, followed by simulated reperfusion for 22 hours. Cell
      viability was assessed by cell counting kit-8 assay. Expression levels of NOX2,
      connexin 43 and caspase-3 were assessed by western blot assay. Reactive oxygen
      species were measured spectrophotometrically. Pretreatment with 10 or 50 MUM
      scutellarin substantially increased viability, reduced the expression of NOX2 and
      caspase-3, increased the expression of connexin 43, and diminished the levels of
      reactive oxygen species in astrocytes subjected to ischemia-reperfusion. We also
      assessed the effects of scutellarin in vivo in the rat transient middle cerebral
      artery occlusion model of cerebral ischemia-reperfusion injury. Rats were given
      intraperitoneal injection of 100 mg/kg scutellarin 2 hours before surgery. The
      Bederson scale was used to assess neurological deficit, and 2,3,5
      triphenyltetrazolium chloride staining was used to measure infarct size. Western
      blot assay was used to assess expression of NOX2 and connexin 43 in brain tissue.
      Enzyme-linked immunosorbent assay was used to detect 8-hydroxydeoxyguanosine (8
      OHdG), 4-hydroxy-2-nonenal (4-HNE) and 3-nitrotyrosin (3-NT) in brain tissue.
      Immunofluorescence double staining was used to determine the co-expression of
      caspase-3 and NeuN. Pretreatment with scutellarin improved the neurological
      function of rats with focal cerebral ischemia, reduced infarct size, diminished
      the expression of NOX2, reduced levels of 8-OHdG, 4-HNE and 3-NT, and reduced the
      number of cells co-expressing caspase-3 and NeuN in the injured brain tissue.
      Furthermore, we examined the effect of the NOX2 inhibitor apocynin. Apocynin
      substantially increased connexin 43 expression in vivo and in vitro.
      Collectively, our findings suggest that scutellarin protects against ischemic
      injury in vitro and in vivo by downregulating NOX2, upregulating connexin 43,
      decreasing oxidative damage, and reducing apoptotic cell death.

PMID- 30106053
TI  - Gualou Guizhi decoction promotes neurological functional recovery and
      neurogenesis following focal cerebral ischemia/reperfusion.
AB  - Recovery following stroke involves neurogenesis and axonal remodeling within the
      ischemic brain. Gualou Guizhi decoction (GLGZD) is a Chinese traditional medicine
      used for the treatment of post-stroke limb spasm. GLGZD has been reported to have
      neuroprotective effects in cerebral ischemic injury. However, the effects of
      GLGZD on neurogenesis and axonal remodeling following cerebral ischemia remain
      unknown. In this study, a rat model of focal cerebral ischemia/reperfusion was
      established by middle cerebral artery occlusion. Neurological function was
      assessed immediately after reperfusion using Longa's 5-point scoring system. The
      rats were randomly divided into vehicle and GLGZD groups. Rats in the sham group
      were given sham operation. The rats in the GLGZD group were intragastrically
      administered GLGZD, once daily, for 14 consecutive days. The rats in the vehicle
      and sham groups were intragastrically administered distilled water. Modified
      neurological severity score test, balance beam test and foot fault test were used
      to assess motor functional changes. Nissl staining was performed to evaluate
      histopathological changes in the brain. Immunofluorescence staining was used to
      examine cell proliferation using the marker 5-bromo-2'-deoxyuridine (BrdU) as
      well as expression of the neural precursor marker doublecortin (DCX), the
      astrocyte marker glial fibrillary acidic protein (GFAP) and the axon regeneration
      marker growth associated protein-43 (GAP-43). GLGZD substantially mitigated
      pathological injury, increased the number of BrdU, DCX and GFAP-immunoreactive
      cells in the subventricular zone of the ischemic hemisphere, increased GAP-43
      expression in the cortical peri-infarct region, and improved motor function.
      These findings suggest that GLGZD promotes neurological functional recovery by
      increasing cell proliferation, enhancing axonal regeneration, and increasing the
      numbers of neuronal precursors and astrocytes in the peri-infarct area.

PMID- 30106055
TI  - Acupuncture through Baihui (DU20) to Qubin (GB7) mitigates neurological
      impairment after intracerebral hemorrhage.
AB  - Inflammation plays an important role in nerve defects caused by intracerebral
      hemorrhage. Repairing brain damage by inhibiting the macrophage-inducible C-type
      lectin/spleen tyrosine kinase (Mincle/Syk) signaling pathway is a potential new
      target for treating cerebral hemorrhage. In this study, we aimed to determine
      whether acupuncture through Baihui (DU20) to Qubin (GB7) is an effective
      treatment for intracerebral hemorrhage through the Mincle/Syk signaling pathway.
      An intracerebral hemorrhage rat model was established by autologous blood
      infusion into the caudate nucleus. Acupuncture through Baihui to Qubin was
      performed for 30 minutes, once every 12 hours, for a total of three times.
      Piceatannol (34.62 mg/kg), a Syk inhibitor, was intraperitoneally injected as a
      control. Modified neurological severity score was used to assess neurological
      function. Brain water content was measured. Immunohistochemistry and western blot
      assay were used to detect immunoreactivity and protein expression levels of
      Mincle, Syk, and CARD9. Real-time polymerase chain reaction was used to determine
      interleukin-1beta mRNA levels. Hematoxylin-eosin staining was performed to
      observe histopathological changes. Our results showed that acupuncture through
      Baihui to Qubin remarkably improved neurological function and brain water
      content, and inhibited immunoreactivity and expression of Mincle, Syk, CARD9, and
      interkeukin-1beta. Moreover, this effect was similar to piceatannol. These
      findings suggest that acupuncture through Baihui to Qubin can improve
      neurological impairment after cerebral hemorrhage by inhibiting the Mincle/Syk
      signaling pathway.

PMID- 30106054
TI  - Xuefu Zhuyu decoction improves neurological dysfunction by increasing synapsin
      expression after traumatic brain injury.
AB  - Xuefu Zhuyu decoction has been used for treating traumatic brain injury and
      improving post-traumatic dysfunction, but its mechanism of action needs further
      investigation. This study established rat models of traumatic brain injury by
      controlled cortical impact. Rat models were intragastrically administered 9 and
      18 g/kg Xuefu Zhuyu decoction once a day for 14 or 21 days. Changes in
      neurological function were assessed by modified neurological severity scores and
      the Morris water maze. Immunohistochemistry, western blot assay, and reverse
      transcription polymerase chain reaction were used to analyze synapsin protein and
      mRNA expression at the injury site of rats. Our results showed that Xuefu Zhuyu
      decoction visibly improved neurological function of rats with traumatic brain
      injury. These changes were accompanied by increased expression of synaptophysin,
      synapsin I, and postsynaptic density protein-95 protein and mRNA in a dose
      dependent manner. These findings indicate that Xuefu Zhuyu decoction increases
      synapsin expression and improves neurological deficits after traumatic brain
      injury.

PMID- 30106056
TI  - Selenocysteine antagonizes oxygen glucose deprivation-induced damage to
      hippocampal neurons.
AB  - Designing and/or searching for novel antioxidants against oxygen glucose
      deprivation (OGD)-induced oxidative damage represents an effective strategy for
      the treatment of human ischemic stroke. Selenium is an essential trace element,
      which is beneficial in the chemoprevention and chemotherapy of cerebral ischemic
      stroke. The underlying mechanisms for its therapeutic effects, however, are not
      well documented. Selenocysteine (SeC) is a selenium-containing amino acid with
      neuroprotective potential. Studies have shown that SeC can reduce irradiation
      induced DNA apoptosis by reducing DNA damage. In this study, the in vitro
      protective potential and mechanism of action of SeC against OGD-induced apoptosis
      and neurotoxicity were evaluated in HT22 mouse hippocampal neurons. We cultured
      HT22 cells in a glucose-free medium containing 2 mM Na2S4O2, which formed an OGD
      environment, for 90 minutes. Findings from MTT, flow cytometry and TUNEL staining
      showed obvious cytotoxicity and apoptosis in HT22 cells in the OGD condition. The
      activation of Caspase-7 and Caspase-9 further revealed that OGD-induced apoptosis
      of HT22 cells was mainly achieved by triggering a mitochondrial-mediated pathway.
      Moreover, the OGD condition also induced serious DNA damage through the
      accumulation of reactive oxygen species and superoxide anions. However, SeC pre
      treatment for 6 hours effectively inhibited OGD-induced cytotoxicity and
      apoptosis in HT22 cells by inhibiting reactive oxygen species-mediated oxidative
      damage. Our findings provide evidence that SeC has the potential to suppress OGD
      induced oxidative damage and apoptosis in hippocampal neurons.

PMID- 30106057
TI  - Effect of Graphene Nanoribbons (TexasPEG) on locomotor function recovery in a rat
      model of lumbar spinal cord transection.
AB  - A sharply transected spinal cord has been shown to be fused under the
      accelerating influence of membrane fusogens such as polyethylene glycol (PEG)
      (GEMINI protocol). Previous work provided evidence that this is in fact possible.
      Other fusogens might improve current results. In this study, we aimed to assess
      the effects of PEGylated graphene nanoribons (PEG-GNR, and called "TexasPEG" when
      prepared as 1wt% dispersion in PEG600) versus placebo (saline) on locomotor
      function recovery and cellular level in a rat model of spinal cord transection at
      lumbar segment 1 (L1) level. In vivo and in vitro experiments (n = 10 per
      experiment) were designed. In the in vivo experiment, all rats were submitted to
      full spinal cord transection at L1 level. Five weeks later, behavioral assessment
      was performed using the Basso Beattie Bresnahan (BBB) locomotor rating scale.
      Immunohistochemical staining with neuron marker neurofilament 200 (NF200)
      antibody and astrocytic scar marker glial fibrillary acidic protein (GFAP) was
      also performed in the injured spinal cord. In the in vitro experiment, the
      effects of TexasPEG application for 72 hours on the neurite outgrowth of SH-SY5Y
      cells were observed under the inverted microscope. Results of both in vivo and in
      vitro experiments suggest that TexasPEG reduces the formation of glial scars,
      promotes the regeneration of neurites, and thereby contributes to the recovery of
      locomotor function of a rat model of spinal cord transfection.

PMID- 30106058
TI  - Local inhibition of matrix metalloproteinases reduced M2 macrophage activity and
      impeded recovery in spinal cord transected rats after treatment with fibroblast
      growth factor-1 and nerve grafts.
AB  - Alternatively activated macrophages (M2 macrophages) promote central nervous
      system regeneration. Our previous study demonstrated that treatment with
      peripheral nerve grafts and fibroblast growth factor-1 recruited more M2
      macrophages and improved partial functional recovery in spinal cord transected
      rats. The migration of macrophages is matrix metalloproteinase (MMP) dependent.
      We used a general inhibitor of MMPs to influence macrophage migration, and we
      examined the migration of macrophage populations and changes in spinal function.
      Rat spinal cords were completely transected at T8, and 5 mm of spinal cord was
      removed (group T). In group R, spinal cord-transected rats received treatment
      with fibroblast growth factor-1 and peripheral nerve grafts. In group RG, rats
      received the same treatment as group R with the addition of 200 MUM GM6001 (an
      MMP inhibitor) to the fibrin mix. We found that MMP-9, but not MMP-2, was
      upregulated in the graft area of rats in group R. Local application of the MMP
      inhibitor resulted in a reduction in the ratio of arginase-1 (M2 macrophage
      subset)/inducible nitric oxide synthase-postive cells. When the MMP inhibitor was
      applied at 8 weeks postoperation, the partial functional recovery observed in
      group R was lost. This effect was accompanied by a decrease in brain-derived
      neurotrophic factor levels in the nerve graft. These results suggested that the
      arginase-1 positive population in spinal cord transected rats is a migratory cell
      population rather than the phenotypic conversion of early iNOS+ cells and that
      the migration of the arginase-1+ population could be regulated locally.
      Simultaneous application of MMP inhibitors or promotion of MMP activity for
      spinal cord injury needs to be considered if the coadministered treatment
      involves M2 recruitment.

PMID- 30106059
TI  - Novel conductive polypyrrole/silk fibroin scaffold for neural tissue repair.
AB  - Three dimensional (3D) bioprinting, which involves depositing bioinks (mixed
      biomaterials) layer by layer to form computer-aided designs, is an ideal method
      for fabricating complex 3D biological structures. However, it remains challenging
      to prepare biomaterials with micro-nanostructures that accurately mimic the
      nanostructural features of natural tissues. A novel nanotechnological tool,
      electrospinning, permits the processing and modification of proper nanoscale
      biomaterials to enhance neural cell adhesion, migration, proliferation,
      differentiation, and subsequent nerve regeneration. The composite scaffold was
      prepared by combining 3D bioprinting with subsequent electrochemical deposition
      of polypyrrole and electrospinning of silk fibroin to form a composite
      polypyrrole/silk fibroin scaffold. Fourier transform infrared spectroscopy was
      used to analyze scaffold composition. The surface morphology of the scaffold was
      observed by light microscopy and scanning electron microscopy. A digital
      multimeter was used to measure the resistivity of prepared scaffolds. Light
      microscopy was applied to observe the surface morphology of scaffolds immersed in
      water or Dulbecco's Modified Eagle's Medium at 37 degrees C for 30 days to assess
      stability. Results showed characteristic peaks of polypyrrole and silk fibroin in
      the synthesized conductive polypyrrole/silk fibroin scaffold, as well as the
      structure of the electrospun nanofiber layer on the surface. The electrical
      conductivity was 1 * 10-5-1 * 10-3 S/cm, while stability was 66.67%. A 3-(4,5
      dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was employed to
      measure scaffold cytotoxicity in vitro. Fluorescence microscopy was used to
      observe EdU-labeled Schwann cells to quantify cell proliferation.
      Immunohistochemistry was utilized to detect S100beta immunoreactivity, while
      scanning electron microscopy was applied to observe the morphology of adherent
      Schwann cells. Results demonstrated that the polypyrrole/silk fibroin scaffold
      was not cytotoxic and did not affect Schwann cell proliferation. Moreover,
      filopodia formed on the scaffold and Schwann cells were regularly arranged. Our
      findings verified that the composite polypyrrole/silk fibroin scaffold has good
      biocompatibility and may be a suitable material for neural tissue engineering.

PMID- 30106060
TI  - Three-dimensional visualization of the functional fascicular groups of a long
      segment peripheral nerve.
AB  - : The three-dimensional (3D) visualization of the functional bundles in the
      peripheral nerve provides direct and detailed intraneural spatial information. It
      is useful for selecting suitable surgical methods to repair nerve defects and in
      optimizing the construction of tissue-engineered nerve grafts. However, there
      remain major technical hurdles in obtaining, registering and interpreting 2D
      images, as well as in establishing 3D models. Moreover, the 3D models are plagued
      by poor accuracy and lack of detail and cannot completely reflect the
      stereoscopic microstructure inside the nerve. To explore and help resolve these
      key technical problems of 3D reconstruction, in the present study, we designed a
      novel method based on re-imaging techniques and computer image layer processing
      technology. A 20-cm ulnar nerve segment from the upper arm of a fresh adult
      cadaver was used for acetylcholinesterase (AChE) staining. Then, 2D panoramic
      images were obtained before and after AChE staining under the stereomicroscope.
      Using layer processing techniques in Photoshop, a space transformation method was
      used to fulfill automatic registration. The contours were outlined, and the 3D
      rendering of functional fascicular groups in the long-segment ulnar nerve was
      performed with Amira 4.1 software. The re-imaging technique based on layer
      processing in Photoshop produced an image that was detailed and accurate. The
      merging of images was accurate, and the whole procedure was simple and fast. The
      least square support vector machine was accurate, with an error rate of only
      8.25%. The 3D reconstruction directly revealed changes in the fusion of different
      nerve functional fascicular groups. IN CONCLUSION: The technique is fast with
      satisfactory visual reconstruction.

PMID- 30106061
TI  - Analgesic effect of AG490, a Janus kinase inhibitor, on oxaliplatin-induced acute
      neuropathic pain.
AB  - Neuropathic pain often occurs during chemotherapy with oxaliplatin. AG490 has
      been shown to exert an antagonistic effect on inflammatory pain, but its effect
      on oxaliplatin-induced neuropathic pain remains poorly understood. This study
      sought to observe the analgesic effect of AG490 on acute neuropathic pain induced
      by a single oxaliplatin treatment and to address the possible mechanism. In this
      study, we established a model of oxaliplatin-induced acute neuropathic pain by
      intraperitoneal injection of 6 mg/kg oxaliplatin. On day 2 after injection,
      models were intraperitoneally injected with 1, 5, or 10 mg/kg AG490. Paw
      withdrawal threshold to mechanical stimuli and tail withdrawal latency to cold
      stimuli were determined. Western blot assay was performed to detect the
      expression of spinal phosphorylated signal transducer and activator of
      transcription 3 (p-STAT3). Immunohistochemistry was used to determine the
      immunoreactivity of p-STAT3 and interleukin-6. Results demonstrated that paw
      withdrawal threshold and tail withdrawal latency were significantly increased by
      the treatment of AG490 in rats. There was no significant difference in the effect
      among the different doses of AG490. AG490 10 mg/kg decreased the expression of p
      STAT3, the immunoreactivity of p-STAT3 and interleukin-6 in spinal cord of acute
      neuropathic pain rats. These findings confirm that AG490 can attenuate
      oxaliplatin-induced acute neuropathic pain and is associated with the inhibition
      in the JAK/STAT3 signaling pathway.

PMID- 30106063
TI  - Reorganization of injured anterior cingulums in a hemorrhagic stroke patient.

PMID- 30106062
TI  - A novel chronic nerve compression model in the rat.
AB  - Current animal models of chronic peripheral nerve compression are mainly silicone
      tube models. However, the cross section of the rat sciatic nerve is not a perfect
      circle, and there are differences in the diameter of the sciatic nerve due to
      individual differences. The use of a silicone tube with a uniform internal
      diameter may not provide a reliable and consistent model. We have established a
      chronic sciatic nerve compression model that can induce demyelination of the
      sciatic nerve and lead to atrophy of skeletal muscle. In 3-week-old pups and
      adult rats, the sciatic nerve of the right hind limb was exposed, and a piece of
      surgical latex glove was gently placed under the nerve. N-butyl-cyanoacrylate was
      then placed over the nerve, and after it had set, another piece of glove latex
      was placed on top of the target area and allowed to adhere to the first piece to
      form a sandwich-like complex. Thus, a chronic sciatic nerve compression model was
      produced. Control pups with latex or N-butyl-cyanoacrylate were also prepared.
      Functional changes to nerves were assessed using the hot plate test and
      electromyography. Immunofluorescence and electron microscopy analyses of the
      nerves were performed to quantify the degree of neuropathological change. Masson
      staining was conducted to assess the degree of fibrosis in the gastrocnemius and
      intrinsic paw muscles. The pup group rats subjected to nerve compression
      displayed thermal hypoesthesia and a gradual decrease in nerve conduction
      velocity at 2 weeks after surgery. Neuropathological studies demonstrated that
      the model caused nerve demyelination and axonal irregularities and triggered
      collagen deposition in the epineurium and perineurium of the affected nerve at 8
      weeks after surgery. The degree of fibrosis in the gastrocnemius and intrinsic
      paw muscles was significantly increased at 20 weeks after surgery. In conclusion,
      our novel model can reproduce the functional and histological changes of chronic
      nerve compression injury that occurs in humans and it will be a useful new tool
      for investigating the mechanisms underlying chronic nerve compression.

PMID- 30106065
TI  - Six-Week Pelvic Floor Muscle Activity (sEMG) Training in Pregnant Women as
      Prevention of Stress Urinary Incontinence.
AB  - BACKGROUND Pelvic floor muscle exercises are a widely used and well-established
      form of stress incontinence treatment, with success rates varying from 21% to
      84%, although with a better subjective than objective outcome. MATERIAL AND
      METHODS "Incontinence Impact Questionnaire" (IIQ), PFM EMG assessment was done at
      the beginning and after the 6-week training program. RESULTS Statistically
      significant differences appeared in the BASE and R values. In the symptomatic
      group (with SUI symptoms), the value of BASE was 3.26 uV, and after training it
      was 3.95 uV. The R values before and after training were 4.55 uV and 4.25 uV. In
      the symptomatic group (without SUI symptoms), the value of BASE was 2.88 uV and
      3.52 uV and R values were 7.16 uV and 3.92 uV. In the control group, BASE was
      3.05 uV and 4.11 uV and R was 7.82 uV and 4.39 uV. CONCLUSIONS The results
      indicate that a 6-week training process influences PFM EMG activity in pregnant
      women. During Q, the value of PFM activity after a training session tended to
      increase in the symptomatic and control groups, but in the symptomatic group it
      remains practically unchanged. Our results show the probable process of
      decreasing control of PFM activity during long-lasting contractions in
      symptomatic and control women. The comparison of BASE before and after training
      averaged the values of R after five 10-s contractions and showed an increase in
      the Base and decrease in the R.

PMID- 30106067
TI  - Naturally occurring quaternary benzo[c]phenanthridine alkaloids selectively
      stabilize G-quadruplexes.
AB  - In this work, the interaction of six natural benzo[c]phenanthridine alkaloids
      (macarpine, sanguilutine, sanguirubine, chelerythrine, sanguinarine and
      chelirubine) with parallel and antiparallel G-quadruplex DNA structures was
      studied. HT22 corresponding to the end of human telomeres and the modified
      promoter oncogene c-kit21 and Pu22 sequences have been used. Spectroscopically
      monitored melting experiments and fluorescence titrations, competitive dialysis
      and nuclear magnetic resonance spectroscopy were used for this purpose. The
      results showed that these alkaloids stabilized G-quadruplex structures in terms
      of increments of Tm values (from 15 to 25  degrees C) with high selectivity over
      duplexes and unfolded DNA. The mode of binding was mainly by stacking on the
      terminal G-tetrads with stoichiometries of 1 : 2 (DNA : ligand). The presence of
      non-specific electrostatic interactions was also observed. Overall, the results
      pointed to a strong stabilization of G-quadruplex structures by these alkaloids.

PMID- 30106066
TI  - [Effect of employment and domestic load on fetal development and length of
      gestation in a birth cohort study].
AB  - OBJECTIVE: Published studies are not conclusive on the impact of certain
      occupational exposures in pregnancy, stressing the need to consider the double
      role, professional and family, of women. The objective of this study is to
      evaluate the effect of employment and domestic load on the duration of pregnancy
      and fetal development. METHODS: Using Univariate and Multivariate regression
      models, we studied the association of preterm deliveries (PPT) (<37 weeks), full
      term newborns with low weight (BPT) (<2500g) and small for their gestational age
      (PEG) (<10th percentile) in weight, length and head circumference according to
      work situation (employment/non-employment) and domestic load (low/ medium/ high)
      in 2506 women. The analyses were carried out using SPSS and R. RESULTS: Women
      with medium domestic load have lower risk of PPT (OR=0.41, 95%CI:0.21-0.81), PEG
      in weight (OR=0.47, 95%CI:0.32-0.69), length (OR=0.57, 95%CI:0.39-0.83) and head
      circumference (OR=0.58, 95% CI:0.40-0.83) and with high load PEG in weight
      (OR=0.72,95%CI:0.54-0.98) and head circumference (OR = 0.73, 95% CI:0.54-0.99).
      When analyzing employment situation and domestic load, women with medium domestic
      load have less risk of PPT (OR=0.29, 95%CI:0.14-0.58) than the absence of load or
      high domestic load. CONCLUSIONS: The results show a protective effect of the
      medium and high domestic load, reducing the probability of preterm birth and
      small for gestational age babies.

PMID- 30106068
TI  - A 2D ferromagnetic semiconductor in monolayer Cr-trihalide and its Janus
      structures.
AB  - Using first principles calculations, we explored the physical properties of two
      dimensional (2D) Cr-trihalide X3-Cr2-X3 or CrX3 (X = Cl, Br, I) and its Janus
      monolayers X3-Cr2-Y3 (X and Y = Cl, Br, I) where X ? Y. We found that Janus
      monolayer X3-Cr2-Y3 materials are dynamically stable and that it is feasible to
      synthesize X3-M2-Y3 2D-crystals. Both pristine and Janus layers have intrinsic
      two-dimensional ferromagnetic semiconducting band structures; the largest band
      gap of 2.3 eV was found in Cl3-Cr2-Cl3, while the band gaps decreased in heavier
      halide systems. Using Monte Carlo simulations, we found that the Curie
      temperatures (Tc) showed the same feature of strong dependence on the X and Y
      halides. In non-polar systems with X = Y, we found no dipole moment, while the
      polar systems with X ? Y had induced dipole moments. Thus, the pristine layer has
      the same function on both sides, while the Janus layer displays dissimilar work
      functions in two different surface directions; this was related to the dipole
      moment and the value of electronegativity. We found that both pristine and Janus
      layer systems displayed rather weak frequency-dependent dielectric functions.
      Thus, the variation of the refractive index with frequency was small, and almost
      zero reflectivity was found in all systems.

PMID- 30106069
TI  - First-principles database driven computational neural network approach to the
      discovery of active ternary nanocatalysts for oxygen reduction reaction.
AB  - An elegant machine-learning-based algorithm was applied to study the thermo
      electrochemical properties of ternary nanocatalysts for oxygen reduction reaction
      (ORR). High-dimensional neural network potentials (NNPs) for the interactions
      among the components were parameterized from big dataset established by first
      principles density functional theory calculations. The NNPs were then
      incorporated with Monte Carlo (MC) and molecular dynamics (MD) simulations to
      identify not only active, but also electrochemically stable nanocatalysts for ORR
      in acidic solution. The effects of surface strain caused by selective segregation
      of certain components on the catalytic performance were accurately characterized.
      The computationally efficient and precise approach proposes a promising ORR
      candidate: 2.6 nm icosahedron comprising 60% of Pt and 40% Ni/Cu. Our methodology
      can be applied for high-throughput screening and designing of key functional
      nanomaterials to drastically enhance the performance of various electrochemical
      systems.

PMID- 30106070
TI  - Time-dependent shotgun proteomics revealed distinct effects of an organoruthenium
      prodrug and its activation product on colon carcinoma cells.
AB  - Activation kinetics of metallo-prodrugs control the types of possible
      interactions with biomolecules. The intact metallo-prodrug is able to engage with
      potential targets by purely non-covalent bonding, while the activated metallodrug
      can form additional coordination bonds. It is hypothesized that the additional
      coordinative bonding might be favourable with respect to the target selectivity
      of activated metallodrugs. Thus, a time-dependent shotgun proteomics study was
      conducted in HCT116 colon carcinoma cells with plecstatins, which are
      organoruthenium anticancer drug candidates. First, the target selectivity was
      evaluated in a time-dependent fashion, which accounted for their hydrolysis
      kinetics. The binding selectivity increased from 50- to 160-fold and the average
      specificity from 0.72 to 0.86, respectively, from the 2 h to the 4 h target
      profiling experiment. Target profiling after 19 h did not reveal significant
      enrichments, possibly due to deactivation of the probe via arene cleavage. Up to
      450 interactors were identified in the target profiling experiments. A plecstatin
      analogue that substituted a hydrogen bond acceptor with a hydrogen bond donor
      abrogated the target selectivity for plectin in HCT116 whole cell lysates,
      underlining the necessity of this hydrogen bond acceptor for a strong interaction
      between plecstatin and plectin. Second, time-dependent response profiling
      experiments provided evidence that plecstatin-2 induced an integrated stress
      response (ISR) in HCT116 cell culture. The phosphorylation of eIF2alpha, a key
      mediator of the ISR, after 3 h treatment indicated that this perturbation was
      initiated by the intact plecstatin-2 prodrug, while the effects of plectin
      targeting are mediated by activated plecstatin-2.

PMID- 30106071
TI  - Low-temperature solution-processed vanadium oxide as hole transport layer for
      efficient and stable perovskite solar cells.
AB  - In recent years, great progress has been achieved in improving the power
      conversion efficiency (PCE) of organic-inorganic hybrid perovskite solar cells
      (PSCs), but the stability of PSCs is still an obstacle in their commercialization
      due to the limitation of efficient and stable hole transport materials. Herein,
      we demonstrate an alcohol-solution-based low-temperature-processed vanadium oxide
      (VOx) hole transport layer (HTL) for planar heterojunction PSCs. The good
      crystallinity and morphology of CH3NH3PbI3 grown on this amorphous VOx film is
      investigated by scanning electron microscopy (SEM) and X-ray diffraction (XRD)
      techniques. Due to the suitable and matching energy levels of VOx and CH3NH3PbI3,
      the holes generated in CH3NH3PbI3 can efficiently transfer to VOx HTL.
      Furthermore, VOx-HTL-based PSCs yield a PCE value of 14.5% with better stability
      in comparison with PEDOT:PSS-HTL-based PSCs. These results reveal that the low
      temperature-processed VOx films can be employed as the HTL for efficient and
      stable PSCs.

PMID- 30106072
TI  - Diversity among endothelial cell lines revealed by Raman and Fourier-transform
      infrared spectroscopic imaging.
AB  - Growing interest in the role of endothelium under physiological and pathological
      conditions has led to an increasing demand for its representative in vitro models
      especially suitable for drug tests and medical diagnostics. There are several
      endothelial cell lines commercially available whose biochemistry, and hence
      response to various stimuli, can be different. Recently, two vibrational
      techniques, Raman and Fourier-transform infrared microscopy, have been found to
      be potent tools for studying the biochemical composition of a single cell in an
      easy, rapid and label-free way. However, depending on the applied technique, the
      results may exhibit some divergence due to different selection rules as well as
      distinct experimental conditions. This paper presents the methodology of
      examination and characterization of three popular human endothelial cell lines:
      HAoEC (primary cells), HMEC-1 and EA.hy926 (immortalized cells). Based on high
      lateral resolution Raman imaging together with standard and high magnification
      Fourier-transform infrared measurements, the differences in spectral information
      and the distribution of biomolecules are presented and discussed.

PMID- 30106073
TI  - MoO3 nanosheet arrays as superior anode materials for Li- and Na-ion batteries.
AB  - MoO3 is a promising anode material for energy storage, but its electrochemical
      performance is still unsatisfactory. Herein, alpha-MoO3 nanosheets vertically
      grown on activated carbon fiber cloth as superior anode materials for Li- and Na
      ion batteries were achieved by the method of controlled preparation. For Li-ion
      batteries, the resulting MoO3 array electrodes exhibit a high discharge capacity
      of 4.48 mA h cm-2 (1780 mA h g-1) at 0.1 mA cm-2 and outstanding cycling
      stability at 0.5 mA cm-2 (94% capacity retention after 200 cycles). Moreover, for
      Na-ion batteries, they also show an excellent electrochemical performance with a
      discharge capacity of 2.5 mA h cm-2 (1621 mA h g-1) at 0.1 mA cm-2 and capacity
      retention of 90% after 200 cycles at 0.2 mA cm-2. This study suggests that MoO3
      array electrodes can be hopefully used as promising anode materials for energy
      storage applications.

PMID- 30106074
TI  - Effect of nanosilver surfaces on peptide reactivity towards reactive oxygen
      species.
AB  - The interaction of a terminal tryptophan residue within collagen mimetic peptides
      when tethered to nanometric silver surfaces was studied using a combination of
      steady state spectroscopy, ultrafast spectroscopy, and molecular dynamics
      experiments. Our findings indicate that the effective interaction between the
      tryptophan and the metal surface occurs in short-time scales (ps) and it is
      responsible for improving the colloidal stability of the nanoparticles exposed to
      free radicals. The extent and efficiency of the interaction depends on factors
      beyond the peptide length that include conformation and distance from the
      terminal tryptophan to the metal surface.

PMID- 30106075
TI  - A comparative study on a flexible ZnO-based nano-generator using Schottky and p-n
      junction contact for energy harvesting applications.
AB  - Vibration based piezoelectric energy harvesting from unused ambient sources is an
      efficient approach for a battery-free, sustainable and green power source for
      self-powered electronics. This paper presents the performance enhancement of a p
      n junction based flexible nano-generator (NG). A stable, non-hazardous spiro and
      zinc oxide (ZnO) p-n junction based NG is proposed. The device performance is
      compared with a Schottky contact based NG. The experimental study is carried out
      using the tip excitation method. Most importantly, the contact modification with
      spiro improves the performance of the device by five times, thereby yielding an
      open circuit voltage of 300 mV, a short-circuit current density of 220 MUA cm-2
      and a maximum power density up to 48 MUW cm-2 at 0.5 N. Furthermore, performance
      enhancement is achieved by reducing the external screening and the internal
      impedance. The results are validated using an RC time constant value derived from
      the impedance analysis.

PMID- 30106076
TI  - Boosting visible-light photocatalytic H2 evolution via UiO-66-NH2 octahedrons
      decorated with ultrasmall NiO nanoparticles.
AB  - Metal-organic framework (MOF)-based materials possess numerous attractive
      characteristics; however, the application of MOF-based photocatalysts in the area
      of visible-light photocatalytic H2 evolution is still in its infancy. Herein, we
      develop a series of novel UiO-66-NH2-based composites with embedded NiO
      nanoparticles via solvothermal treatment and subsequent calcination. Their
      characterizations demonstrate intimate lattice-level contacts between UiO-66-NH2
      photocatalysts and NiO nanoparticles. By optimizing each component, even without
      noble metal loading, the U6N-NiO-2 sample (the weight ratio of NiO to U6N-NiO-2
      is theoretically calculated to be ca. 10 wt%) with 15 mg eosin Y as a sensitizer
      causes an enhanced H2 generation rate of 2561.32 MUmol h-1 g-1 under visible
      light irradiation using TEOA as a sacrificial reagent; furthermore, its
      corresponding quantum efficiency is as high as 6.4% at 420 nm. The H2 evolution
      activity of U6N-NiO-2 is about 5 times higher than that of the UiO-66-NH2
      photocatalyst (denoted as U6N) and 23 times higher than that of U6N-NiO-2 without
      sensitizer. It is demonstrated that the high efficiency originates from the
      visible-light generated electrons of eosin Y and UiO-66-NH2, the efficient
      separation of carriers by the cascaded band structure and more negative CB of NiO
      as well as the good dispersion of NiO nanoparticles on the octahedral skeleton.
      This study provides new insights for the design of MOF-based materials without
      noble metal loading for visible-light photocatalytic H2 evolution.

PMID- 30106077
TI  - Insertion of germanium atoms in high-nuclearity rhodium carbonyl compounds:
      synthesis, characterization and preliminary biological activity of the
      heterometallic [Rh13Ge(CO)25]3-, [Rh14Ge2(CO)30]2- and [Rh12Ge(CO)27]4- clusters.
AB  - The reaction of the [Rh7(CO)16]3- cluster anion with Ge2+ salts, in different
      stoichiometric ratios and under different atmospheres, leads to the formation of
      new heterometallic Rh-Ge clusters, representing the first known examples of Rh
      carbonyl compounds containing interstitial germanium atoms. More specifically,
      under N2 the reaction progressively affords the new [Rh13Ge(CO)25]3- and
      [Rh14Ge2(CO)30]2- clusters in good yields, with the Ge atoms located in cubic and
      square-anti-prismatic cavities, respectively. However, under a CO atmosphere, the
      [Rh13Ge(CO)25]3- derivative undergoes a significant structural and chemical
      rearrangement giving the new compound, [Rh12Ge(CO)27]4-, where Ge is hosted in an
      icosahedral metal cage. All species have been characterized by IR spectroscopy
      and ESI mass spectrometry, and their structures have been elucidated by single
      crystal X-ray diffraction. Additionally, preliminary biological tests on the
      [Rh13Ge(CO)25]3- and [Rh14Ge2(CO)30]2- clusters show that they are cytotoxic to
      various cell lines.

PMID- 30106078
TI  - Strain engineering of photo-induced phase transformations in Prussian blue
      analogue heterostructures.
AB  - Heterostructures based on Prussian blue analogues (PBA) combining photo- and
      magneto-striction have shown a large potential for the development of light
      induced magnetization switching. However, studies of the microscopic parameters
      that control the transfer of the mechanical stresses across the interface and
      their propagation in the magnetic material are still too scarce to efficiently
      improve the elastic coupling. Here, this coupling strength is tentatively
      controlled by strain engineering in heteroepitaxial PBA core-shell
      heterostructures involving the same Rb0.5Co[Fe(CN)6]0.8.zH2O photostrictive core
      and isostructural shells of similar thickness and variable mismatch with the core
      lattice. The shell deformation and the optical electron transfer at the origin of
      photostriction are monitored by combined in situ and real time synchrotron X-ray
      powder diffraction and X-ray absorption spectroscopy under visible light
      irradiation. These experiments show that rather large strains, up to +0.9%, are
      developed within the shell in response to the tensile stresses associated with
      the expansion of the core lattice upon illumination. The shell behavior is,
      however, complex, with contributions in dilatation, in compression or unchanged.
      We show that a tailored photo-response in terms of strain amplitude and kinetics
      with potential applications for a magnetic manipulation using light requires a
      trade-off between the quality of the interface (which needs a small lattice
      mismatch i.e. a small a-cubic parameter for the shell) and the shell rigidity
      (decreased for a large a-parameter). A shell with a high compressibility that is
      further increased by the presence of misfit dislocations will show a decrease in
      its mechanical retroaction on the photo-switching properties of the core
      particles.

PMID- 30106079
TI  - Time-dependent luminescence loss for individual upconversion nanoparticles upon
      dilution in aqueous solution.
AB  - Single-particle luminescence microscopy is a powerful method to extract
      information on biological systems that is not accessible by ensemble-level
      methods. Upconversion nanoparticles (UCNPs) are a particularly promising
      luminophore for single-particle microscopy as they provide stable, non-blinking
      luminescence and allow the avoidance of biological autofluorescence by their anti
      Stokes emission. Recently, ensemble measurements of diluted aqueous dispersions
      of UCNPs have shown the instability of luminescence over time due to particle
      dissolution-related effects. This can be especially detrimental for single
      particle experiments. However, this effect has never been estimated at the
      individual particle level. Here, the luminescence response of individual UCNPs
      under aqueous conditions is investigated by quantitative wide-field microscopy.
      The particles exhibit a rapid luminescence loss, accompanied by large changes in
      spectral response, leading to a considerable heterogeneity in their luminescence
      and band intensity ratio. Moreover, the dissolution-caused intensity loss is not
      correlated with the initial particle intensity or band ratio, which makes it
      virtually unpredictable. These effects and the subsequent development of their
      heterogeneity can be largely slowed down by adding millimolar concentrations of
      sodium fluoride in buffer. As a consequence, the presented data indicate that
      microscopy experiments employing UCNPs in an aqueous environment should be
      performed under conditions that carefully prevent these effects.

PMID- 30106080
TI  - A ZnO/ZnFe2O4 uniform core-shell heterojunction with a tubular structure modified
      by NiOOH for efficient photoelectrochemical water splitting.
AB  - It is known that heterojunction photoelectrodes can improve light absorption and
      accelerate the separation of photogenerated carriers in the field of
      photoelectrochemical (PEC) water splitting. However, the key to efficient
      photoelectrochemical performance is to build heterojunctions with a narrow band
      gap semiconductor loaded on a wide band gap semiconductor uniformly and densely.
      Herein, a ZnO/ZnFe2O4 uniform core-shell heterojunction photoelectrode is
      prepared by a simple ion etching method. Moreover, the chemical reaction process
      and mechanism are discussed in detail. The ZnO/ZnFe2O4 photoelectrode shows a
      higher photocurrent density (0.29 mA cm-2 at 1.23 V vs. RHE) compared with that
      of ZnO (0.17 mA cm-2 at 1.23 V vs. RHE). Furthermore, the PEC performance of
      ZnO/ZnFe2O4 is optimized by depositing NiOOH; the photocurrent density of
      ZnO/ZnFe2O4/NiOOH is 0.48 mA cm-2 at 1.23 V vs. RHE. The remarkable PEC
      performance of ZnO/ZnFe2O4/NiOOH benefits from the following important factors:
      (i) the uniformity and nanotube structure of the ZnO/ZnFe2O4 heterojunction; (ii)
      the excellent light harvesting ability; and (iii) the reduced photogenerated
      electron-hole pair recombination rate. This work provides new insights into
      designing heterojunction systems for efficient photoelectrochemical water
      splitting.

PMID- 30106081
TI  - Iron oxidation dynamics vs. temperature of synthetic potassic-ferro-richterite: a
      XANES investigation.
AB  - We investigated the oxidation behaviour of a synthetic potassic-ferro-richterite
      up to 750  degrees C by using simultaneous X-ray absorption spectroscopy and X
      ray diffraction experiments with synchrotron radiation. From the X-ray
      diffraction results, we observed an abrupt decrease of cell dimensions at ~335 
      degrees C accompanied by an anomalous increase in the monoclinic cell angle beta.
      From the analysis of the XANES spectra at the iron K-edge, we observed that the
      structural shrinkage is due to the iron oxidation process, coupled to hydrogen
      loss, occurring at ~315  degrees C, slightly before the cell contraction.
      Combining these results with previous studies performed on similar samples by
      single-crystal structure refinement, Mossbauer, high temperature-Fourier
      transform IR and Raman spectroscopies, we show that the temperature evolution in
      Fe-amphiboles is a multi-step process. Following the iron oxidation driven by
      temperature, the structural dynamics in this double-chain silicate is ruled by
      local strains in the ribbon of iron-filled octahedra, mainly due to the
      contraction of the M(1) site.

PMID- 30106082
TI  - Low valent Al(ii)-Al(ii) catalysts as highly active epsilon-caprolactone
      polymerization catalysts: indication of metal cooperativity through DFT studies.
AB  - The present study first describes the reactivity of low valent Al(ii) and Ga(ii)
      complexes of the type (dpp-bian)M-M(dpp-bian) (1, M = Al; 2, Ga; dpp-bian2- = 1,2
      bis-(2,6-iPr2-C6H3)-acenaphthenequinonediamido) with cyclic esters/carbonates
      such as epsilon-caprolactone (CL) and trimethylene carbonate (TMC). CL and TMC
      both readily coordinate to the Al(ii) species 1 to form the corresponding bis
      adducts (dpp-bian)Al(L)-(L)Al(dpp-bian) (3, L = CL; 4, L = TMC), which were
      structurally characterized confirming that the Al(ii)-Al(ii) dimetallic backbone
      retains its integrity in the presence of such cyclic polar substrates. In
      contrast, the less Lewis acidic Ga(ii) analogue 2 shows no reaction in the
      presence of stoichiometric amounts of CL and TMC at room temperature. In
      combination with BnOH, the dinuclear Al(ii) species 1 revealed to be an extremely
      active Al(ii) initiator for the controlled ROP of CL at room temperature,
      outperforming all its Al(iii) congeners reported thus far. Detailed DFT studies
      on the ROP mechanism are consistent with a process occurring thanks to the
      metallic cooperativity between the two Al(ii) proximal (since directly bonded)
      metal centers in 1, which undoubtedly favors the ROP process through bimetallic
      activation and thus rationalizes the unusually high CL ROP activity at room
      temperature.

PMID- 30106083
TI  - Li dopant induces moisture sensitive phase degradation of an all-inorganic
      CsPbI2Br perovskite.
AB  - All-inorganic halide perovskites without volatile components have great potential
      for long term thermal stability. However, the phase stability of all-inorganic
      perovskites is sensitive to moisture and has been seldom studied. In this work,
      the phase stability of alpha-CsPbI2Br was studied in different relative humidity
      conditions. The moisture resistance of alpha-CsPbI2Br can be significantly
      enhanced by using a polymer or organic molecule capping layer including Spiro
      MeOTAD. Although an all-inorganic CsPbI2Br perovskite based device using the
      typical Li salt doped Spiro-MeOTAD layer could offer an efficiency up to 12.6%,
      it exhibited even worse moisture resistance than a bare perovskite film under the
      same ambient conditions. This unusual phenomenon is ascribed to the hygroscopic
      properties of Li-TFSI inducing moisture sensitive phase degradation. Therefore,
      it is desirable to decrease the amount of, or avoid the Li salt, as a dopant for
      stable all-inorganic perovskite solar cells with balanced stability and high
      performance.

PMID- 30106085
TI  - Microarray analysis of miRNAs during hindgut development in rat embryos with
      ethylenethiourea-induced anorectal malformations.
AB  - Anorectal malformations (ARMs) are one of the most common congenital
      malformations of the digestive tract; however, the pathogenesis of this disease
      remains to be fully elucidated. MicroRNAs (miRNAs) are important in
      gastrointestinal development and may be involved in the pathogenesis of ARMs. The
      present study aimed to profile miRNAs and examine their potential functions in
      rats with ethylenethiourea (ETU)-induced ARMs. Pregnant Wistar rats (n=36) were
      divided randomly into ETU-treated and control groups. The rats in the ETU-treated
      group were gavage-fed 1% ETU (125 mg/kg) on gestational day 10 (GD10), whereas
      the control group rats received a corresponding dose of saline. Embryos were
      harvested by cesarean section on GD14, GD15 and GD16. Hindgut tissue was isolated
      from the fetuses for RNA extraction and microarray analysis, followed by
      bioinformatics analysis and reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) validation. Overall, 38 miRNAs were differentially expressed
      (all upregulated) on GD14, 49 (32 upregulated and 17 downregulated) on GD15, and
      42 (all upregulated) on GD16 in the ARM group compared with the normal group. The
      top 18 miRNAs with |log2(fold change)| >4.25 were selected for further
      bioinformatics analysis. Among these miRNAs, five were differentially expressed
      at two time-points and were involved in ARM-associated signaling pathways. The RT
      qPCR analysis revealed that three miRNA (miR), miR-125b-2-3p, miR-92a-2-5p and
      miR-99a-5p, were significantly differentially expressed in rats with ARMs
      compared with the normal group. In conclusion, the results suggested that the
      differential expression of miR-125b-2-3p, miR-92a-2-5p and miR-99a-5p during key
      time-points of anorectal formation in rats may have functions in the pathogenesis
      of ARM.

PMID- 30106084
TI  - Hypoxic preconditioned bone mesenchymal stem cells ameliorate spinal cord injury
      in rats via improved survival and migration.
AB  - The unique hypoxic inflammatory microenvironment observed in the spinal cord
      following spinal cord injury (SCI) limits the survival and efficacy of
      transplanted bone mesenchymal stem cells (BMSCs). The aim of the present study
      was to determine whether hypoxic preconditioning (HP) increased the therapeutic
      effects of BMSC on SCI. BMSCs were pretreated with cobalt chloride (CoCl2) in
      vitro, and the proliferative apoptotic and migratory abilities of these hypoxic
      BMSCs (H-BMSCs) were assessed. BMSCs and H-BMSCs derived from green fluorescent
      protein (GFP) rats were transplanted into SCI rats in vivo. The neurological
      function, histopathology, inflammation, and number and migration of transplanted
      cells were examined. HP significantly enhanced BMSC migration (increased hypoxia
      inducible factor 1alpha and C-X-C motif chemokine receptor 4 expression) and
      tolerance to apoptotic conditions (decreased caspase-3 and increased B-cell
      lymphoma 2 expression) in vitro. In vivo, H-BMSC transplantation significantly
      improved neurological function, decreased spinal cord damage and suppressed the
      inflammatory response associated with microglial activation. The number of GFP
      positive cells in the SCI core and peripheral region of H-BMSC animals was
      increased compared with that in those of BMSC animals, suggesting that HP may
      increase the survival and migratory abilities of BMSCs and highlights their
      therapeutic potential for SCI.

PMID- 30106086
TI  - MicroRNA-214 suppresses propofol-induced neuroapoptosis through activation of
      phosphoinositide 3-kinase/protein kinase B signaling by targeting phosphatase and
      tensin homolog expression.
AB  - The present study aimed to investigate the effects of microRNA (miR)-214 on
      neuroapoptosis induced by propofol and the possible mechanism of its anti
      apoptotic effects. Initially, it was observed that miR-214 expression was
      upregulated in propofol-induced neuroapoptosis rats. Next, propofol-treated nerve
      cells were transfected with miR-214 mimics. The results revealed that miR-214
      overexpression induced apoptosis, inhibited cell proliferation, inhibited cyclin
      D1 protein expression, promoted caspase-3 activity and B-cell lymphoma 2
      associated X protein expression, and enhanced the levels of inflammation factors
      in nerve cells treated with propofol. In addition, miR-214 overexpression
      suppressed phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling by
      targeting the activation of phosphatase and tensin homolog (PTEN) and nuclear
      factor-kappaB expression in nerve cells treated with propofol. Treatment with a
      PTEN inhibitor successfully suppressed the PTEN protein expression and decreased
      the apoptosis of propofol-treated nerve cells subsequent to miR-214
      overexpression through PI3K/Akt signaling. In conclusion, the present study data
      revealed that miR-214 suppressed propofol-induced neuroapoptosis through the
      activation of PI3K/Akt signaling by targeting PTEN expression.

PMID- 30106087
TI  - Synergistic effect of ursodeoxycholic acid on the antitumor activity of sorafenib
      in hepatocellular carcinoma cells via modulation of STAT3 and ERK.
AB  - Sorafenib has been approved for the treatment of advanced stage hepatocellular
      carcinoma but has limited efficacy. Ursodeoxycholic acid exerts cytoprotective
      activities in hepatocytes and is believed to suppress tumorigenesis through cell
      cycle arrest and induction of apoptosis. The present study examined whether co
      treatment with ursodeoxycholic acid has a synergistic effect on the antitumor
      activity of sorafenib in hepatocellular carcinoma cells. Notably, co-treatment
      with both agents more effectively inhibited cell proliferation than sorafenib or
      ursodeoxycholic acid alone. Furthermore, co-treatment inhibited the
      phosphorylation of signal transducer and activator of transcription 3 (STAT3) and
      activated extracellular signal-regulated kinase (ERK), a mitogen-activated
      protein kinase, accompanied by excessive intracellular reactive oxygen species
      generation in hepatocellular carcinoma cells. Thus, chemotherapy with sorafenib
      and ursodeoxycholic combination may be efficacious in hepatocellular carcinoma by
      inhibiting cell proliferation and inducing apoptosis through reactive oxygen
      species-dependent activation of ERK and dephosphorylation of STAT3. The present
      findings may represent a promising therapeutic strategy for patients with
      advanced hepatocellular carcinoma.

PMID- 30106089
TI  - Long noncoding RNA cancer susceptibility candidate 9 promotes doxorubicin
      resistant breast cancer by binding to enhancer of zeste homolog 2.
AB  - The present study aimed to investigate the effect of the long noncoding RNA
      cancer susceptibility candidate 9 (CASC9) on doxorubicin (DOX)-resistant breast
      cancer and to reveal the potential underlying mechanisms. The expression of CASC9
      in breast cancer tissues and cell lines, in addition to drug-resistant breast
      cancer cells (MCF-7/DOX), was detected by reverse transcription-quantitative
      polymerase chain reaction. Subsequently, MCF-7/DOX cells were transfected with
      the silencing vector pS-CASC9, containing enhancer of zeste homolog 2 (EZH2),
      multidrug resistance protein 1 (MDR1) or control small interfering (si)RNAs. The
      viability, apoptosis, migration and invasion of the transfected cells were
      assessed via an MTT assay, flow cytometry and a Transwell assay, respectively.
      The expression levels of apoptosis-associated proteins (apoptosis regulator Bcl
      2, apoptosis regulator BAX, caspase-3 and caspase-9) were determined by western
      blotting. An RNA pull-down assay was performed to identify CASC9-binding
      candidates. In addition, the expression levels of the MDR1 gene and its encoded
      protein, P-glycoprotein, were detected. CASC9 expression was upregulated in
      breast cancer tissues and cell lines, and drug-resistant breast cancer cells.
      CASC9 knockdown significantly inhibited the growth and metastasis of drug
      resistant breast cancer cells, and decreased the half-maximal inhibitory
      concentration DOX in MCF-7/DOX cells. The RNA pull-down assay revealed that CASC9
      engaged EZH2; EZH2 siRNA significantly inhibited the cell growth, metastasis and
      chemoresistance of MCF-7/DOX cells. Additionally, EZH2 may regulate the MDR1
      gene. The present study demonstrated the oncogenic role of CASC9 in drug
      resistant breast cancer by binding to EZH2 and regulating the MDR1 gene.
      Modulation of CASC9 expression may be a promising target in the therapy of breast
      cancer and drug-resistant breast cancer.

PMID- 30106088
TI  - Zfat expression in ZsGreen reporter gene knock-in mice: Implications for a novel
      function of Zfat in definitive erythropoiesis.
AB  - Zinc finger and AT-hook domain containing (Zfat) is a transcriptional regulator
      harboring an AT-hook domain and 18 repeats of a C2H2 zinc-finger motif, which
      binds directly to the proximal region of transcription start sites in Zfat-target
      genes. It was previously reported that deletion of the Zfat gene in mice yields
      embryonic lethality by embryonic day 8.5 and impairs primitive hematopoiesis in
      yolk sac blood islands. In addition, Zfat has been reported to be involved in
      thymic T-cell development and peripheral T-cell homeostasis. In the present
      study, in order to obtain a precise understanding of the expression and function
      of Zfat, a knock-in mouse strain (ZfatZsG/+ mice), which expressed ZsGreen in the
      Zfat locus, was established. ZsGreen signals in tissues and cells of ZfatZsG/+
      mice were examined by flow cytometric and histological analyses. Consistent with
      our previous studies, ZsGreen signals in ZfatZsG/+ mice were detected in the
      embryo and yolk sac blood islands, as well as in thymocytes, B and T cells. In
      the ZfatZsG/+ thymus, ZsGreen+ cells were identified not only in T-cell
      populations but also in thymic epithelial cells, suggesting the role of Zfat in
      antigen-presenting cells during thymic T-cell development. ZsGreen signals were
      observed in definitive erythroid progenitor cells in the fetal liver and adult
      bone marrow of ZfatZsG/+ mice. The proportion of ZsGreen+ cells in these tissues
      was highest at the early stage of erythroid differentiation, suggesting that Zfat
      serves particular roles in definitive erythropoiesis. Histological studies
      demonstrated that ZsGreen signals were detected in the pyramidal cells in the
      hippocampal CA1 region and the Purkinje cells in the cerebellum, suggesting novel
      functions of Zfat in nervous tissues. Taken together, these results indicated
      that the ZfatZsG/+ reporter mouse may be considered a useful tool for elucidating
      the expression and function of Zfat.

PMID- 30106090
TI  - TREK-TRAAK two-pore domain potassium channels protect human retinal pigment
      epithelium cells from oxidative stress.
AB  - The aim of the current study was to explore the potential of TREK-TRAAK two-pore
      domain potassium (K2P) channels in protecting human retinal pigment epithelium
      (hRPE) cells against oxidative stress. hRPE cells were obtained from donors, and
      then cell identification and detection of the expression levels of TREK-TRAAK K2P
      channels in hRPE cells were conducted. Subsequently, tert-butyl hydroperoxide (t
      BH) was used to induce oxidative stress in hRPE cells. Docosahexaenoic acid (DHA)
      was used to stimulate and fluoxetine was used to inhibit the TREK-TRAAK K2P
      channels. The survival rates of hRPE cells under oxidative stress were examined
      using flow cytometry. Apoptosis-associated factors, including Bax, Bcl-2, cleaved
      caspase-3, alphaB-crystallin and their mRNAs, were examined using
      immunofluorescence, western blot and reverse transcription-polymerase chain
      reaction analyses. Variations in the cytoarchitecture were observed by
      immunofluorescence and electron microscopy. The cells examined in the present
      study were identified as hRPE cells. All members in the TREK-TRAAK K2P channel
      family (including TREK-1, TREK-2 and TRAAK) were found to be expressed in hRPE
      cells. Stimulation of TREK-TRAAK K2P channels increased the survival rates of
      hRPE cells under oxidative stress and the levels of intracellular protective
      factors, such as Bcl-2 and alphaB-crystallin. By contrast, inhibition of these
      channels decreased the cell survival rates and increased apoptosis enhancing
      factors, such as Bax and cleaved-caspase-3. Further examination of the
      cytoarchitecture revealed that TREK-TRAAK K2P channels protected the integrity of
      the hRPE cell structure against oxidative stress. In conclusion, the present
      study suggested that the activated TREK-TRAAK K2P channels serve a role in
      protecting hRPE cells against the oxidative stress induced by t-BH, which
      indicated that these K2P channels are potential novel targets in retinal
      protection and provided a new direction for research and therapy in retinal
      degeneration diseases.

PMID- 30106091
TI  - An enhanced RRM2 siRNA delivery to rheumatoid arthritis fibroblast-like
      synoviocytes through a liposome-protamine-DNA-siRNA complex with cell permeable
      peptides.
AB  - Rheumatoid arthritis (RA) is considered to be a systemic autoimmune disease that
      induces systemic complications and progressive disability. It affects a large
      number of people. RA fibroblast-like synoviocytes (RA-FLS) promote the
      progression of RA through the secretion of proinflammatory cytokines and
      increasing invasiveness into the extracellular matrix. Therefore, targeting RA
      FLS represents a potential approach for the treatment of RA. Ribonucleotide
      reductase M2 (RRM2), a critical protein for DNA synthesis and repair, may promote
      the proliferation of cells and inhibit cellular apoptosis. In previous studies it
      has been confirmed that the suppression of RRM2 markedly suppressed the
      proliferation of liver cancer cells. In the present study, a cell permeable
      peptide-conjugated liposome-polycation-DNA (LPD) complex loaded with RRM2 small
      interfering RNA (siRNA) (CCP-LPDR) was developed, aiming to increase the levels
      of apoptosis and inhibit the proliferation of RA-FLS. CCP-LPDR is a small-sized
      molecule (~130 nm) with high encapsulation efficiency of siRNA (>90%) and high
      stability. Furthermore, it was verified that CCP-LPDR markedly suppressed RRM2
      gene and protein expression by ~80%. Notably, CCP-LPDR efficiently targeted RA
      FLS, resulting in a marked decrease in the proliferation and increase in the
      level of apoptosis in RA-FLS. In addition, the levels of proinflammatory
      cytokines tumor necrosis factor-alpha and interleukin-6 were markedly decreased
      in RA-FLS following CCP-LPDR treatment. Therefore, CCP-LPDR may efficiently
      deliver RRM2 to RA-FLS and represent a potential treatment for RA.

PMID- 30106092
TI  - miR-204-5p inhibits the occurrence and development of osteoarthritis by targeting
      Runx2.
AB  - One of the hallmarks of osteoarthritis (OA) development is endochondral
      ossification, in which Runt-related transcription factor-2 (Runx2) is aberrantly
      expressed. Runx2 was previously identified to be regulated by microRNA-204-5p
      (miR-204-5p). The aim of the present study was to investigate the potential
      function of miR-204-5p regulating Runx2 during the development of OA and the
      underlying molecular mechanism. The expression levels of miR-204-5p and Runx2
      were determined in tissue specimens. Rat OA models were established by
      transecting the anterior and posterior cruciate ligaments and removing the
      meniscus. Rats were treated with miR-204-5p agomir and miR-204-5p negative
      control (NC). All in vitro experiments were performed using rat primary
      chondrocytes and the SW-1353 human bone chondrosarcoma cell line. It was
      identified that the expression of miR-204-5p was significantly decreased, whereas
      Runx2 was significantly increased, in human OA tissues compared with in non-OA
      tissues, and levels were inversely associated with each other in primary
      chondrocytes and chondrosarcoma cells. Overexpression of miR-204-5p decreased the
      proliferation of chondrocytes and SW-1353 cells. Using a luciferase reporter
      assay, Runx2 was identified to be a direct target of miR-204-5p in chondrocytes
      and overexpressed miR-204-5p altered the expression of collagens II, X and matrix
      metalloproteinase (MMP)-1 and MMP-13 in primary chondrocytes and SW-1353 cells.
      Histological analysis revealed that miR-204-5p treatment ameliorated the OA-like
      phenotype that is reflected by assessment of cartilage thickness and Mankin's
      score. Runx2 expression was gradually increased as the rats increased in age. At
      10 weeks of miR-204-5p agomir treatment, altered expression levels of collagens
      II and X, cartilage oligomeric matrix protein fragment, aggrecan, MMP-1 and MMP
      13 were observed in the treatment group compared with the NC group. In
      conclusion, the results of the present study indicated that miR-204-5p decreases
      chondrocyte proliferation and ameliorates the OA-like phenotype in rats with
      surgically induced OA by targeting Runx2.

PMID- 30106094
TI  - Long non-coding RNA SNHG20 promotes bladder cancer via activating the Wnt/beta
      catenin signalling pathway.
AB  - The long non-coding RNA, small nucleolar RNA host gene 20 (SNHG20), is involved
      in promoting several common types of human cancer, however, the exact function of
      SNHG20 in the pathogenesis of bladder cancer remains to be elucidated. The
      present study aimed to examine the regulatory mechanism of SNHG20 underlying the
      malignant progression of bladder cancer. Reverse transcription-quantitative
      polymerase chain reaction and western blotting were used to examine mRNA and
      protein expression. Cell survival, proliferation, apoptosis, colony formation,
      migration and invasion were also studied. The resulting data indicated that
      SNHG20 was significantly upregulated in bladder cancer tissues and cell lines,
      compared with its expression in adjacent non-tumour tissues and the SV-HUC-1
      normal urinary tract epithelial cell line, respectively. In addition, the high
      expression of SNHG20 was associated with advanced clinical stage, lymph node
      metastasis, and reduced patient survival rate. The knockdown of SNHG20 caused a
      significant reduction in cancer cell survival, proliferation, colony formation,
      migration and invasion, and induced cell apoptosis. Additionally, the inhibition
      of SNHG20 reduced tumour growth in vivo. Investigations into the mechanism
      revealed that the inhibition of SNHG20 suppressed the activation of Wnt/beta
      catenin signalling and the expression of certain key genes in bladder cancer
      cells. Taken together, these results indicated that SNHG20 is involved in
      promoting bladder cancer and may be used as a potential therapeutic target for
      the treatment of this disease.

PMID- 30106093
TI  - A regulation loop between Nrf1alpha and MRTF-A controls migration and invasion in
      MDA-MB-231 breast cancer cells.
AB  - As a strong transactivator of promoters containing CarG boxes, myocardin-related
      transcription factor A (MRTF-A) is critical for the process of metastasis in
      tumor cells. Nuclear factor erythroid 2-like 1 (Nrf1) is well known as an
      important regulator of oxidative stress, which exists in multiple splicing forms
      with many unknown functions. The present study demonstrated a novel regulation
      loop between Nrf1alpha (the longest splicing form of Nrf1) and MRTF-A that
      regulated the migration and invasion of breast cancer MDA-MB-231 cells. The
      underlying mechanism of this regulation look was further investigated. In
      particular, Nrf1alpha inhibited migration and invasion of breast cancer cells
      through inhibiting the expression of MRTF-A via miR-219. The current results
      revealed that miR-219 could bind to the MRTF-A 3'-UTR to directly regulate its
      expression. However, MRTF-A could reverse activate the Nrf1alpha expression
      through binding to the CarG box in the Nrf1alpha promoter. It can be speculated
      that this regulation loop may be a homeostasis mechanism in cells against
      tumorigenesis.

PMID- 30106095
TI  - Tumor promoter role of miR-647 in gastric cancer via repression of TP73.
AB  - It has previously been demonstrated that miRNA (miR)-647 exhibits an important
      role in various cancers, and is aberrantly expressed in gastric cancer (GC).
      However, the exact role of miR-647 in GC still remains unclear. The present study
      aimed to investigate the functional significance of miR-647 and its target gene
      in GC. TargetScan and Miranda databases were used to predict the putative
      targets, and the prediction was validated by Dual-luciferase Reporter Assays. To
      investigate whether miR-647 affects GC cell behavior, a stable miR-647
      overexpression/low-expression cell line was generated by transfection with miR
      647 mimic/inhibitor. MTT, Flow Cytometry and Transwell invasion assays were
      performed to investigate the proliferation, cell apoptosis, migration and
      invasion properties of MGC-803 cells. Additionally, reverse transcription
      quantitative polymerase chain reaction and western blot analysis were performed
      to detect the mRNA and protein expression levels of the apoptosis-associated
      genes. The results suggested that tumor protein P73 (TP73) is a target gene of
      miR-647. TP73 was markedly decreased following miR-647 overexpression and
      significantly increased following miR-647 inhibition. Following overexpression of
      miR-647, the proliferation, migration and invasion of MGC-803 cells were
      significantly increased, whereas the percentage of apoptotic cells decreased.
      Conversely, the proliferation, migration and invasion of MGC-803 cells were
      significantly declined, and the percentage of apoptotic cells increased following
      miR-647 inhibition. In addition, the B cell lymphoma (Bcl)-2 Associated X,
      Apoptosis Regulator/Bcl-2 ratio was markedly decreased when miR-647 was
      overexpressed by miRNA mimics, and significantly increased when miR-647
      expression was inhibited via an miRNA inhibitor. Overall, miR-647 functions as a
      tumor promoter in GC by repressing TP73.

PMID- 30106096
TI  - Theaflavins attenuate ethanol-induced oxidative stress and cell apoptosis in
      gastric mucosa epithelial cells via downregulation of the mitogen-activated
      protein kinase pathway.
AB  - Ethanol-induced diseases of the gastric mucosa are the most common and refractory
      diseases of gastrointestinal system in clinic, and are mediated by oxidative
      stress and apoptosis pathways. Theaflavins (TFs) are considered to be
      antioxidants. The present study aimed to determine the molecular mechanism
      underlying the ability of TFs to attenuate ethanol-induced oxidative stress and
      apoptosis in GES-1 gastric mucosa epithelial cells. A Cell Counting Kit-8 (CCK-8)
      assay was performed to investigate the cell viability of GES-1 cells following
      administration of ethanol (0.5 mol/l) and subsequent treatment with TFs (20, 40
      and 80 ug/ml) for specific time intervals. A carboxyfluorescein diacetate
      succinimidyl ester assay was used to measure proliferation and further
      investigate the results of the CCK-8 assay. Flow cytometry was performed to
      measure reactive oxygen species (ROS) levels and the apoptosis rates of GES-1
      cells. Furthermore, levels of oxidative stress-associated factors, including
      malondialdehyde, superoxide dismutase and glutathione, were investigated using
      commercial kits. Reverse transcription-quantitative polymerase chain reaction and
      western blot assays were performed to determine the expression levels of
      apoptosis-associated factors, as well as the phosphorylation levels of
      extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and
      p38 kinase (p38). The results of the present study demonstrated that treatment
      with ethanol inhibited GES-1 cell proliferation, and enhanced ROS levels and
      apoptosis rates, potentially via downregulation of B-cell lymphoma-2 (Bcl-2)
      expression and upregulation of Bcl-2-associated X and caspase-3 expression
      levels, as well as enhancing the phosphorylation levels of ERK, JNK and p38.
      However, treatment with TFs was revealed to attenuate the effects of ethanol
      administration on GES-1 cells in a dose-dependent manner. In conclusion, TFs may
      attenuate ethanol-induced oxidative stress and apoptosis in gastric mucosa
      epithelial cells via downregulation of various mitogen-activated protein kinase
      pathways.

PMID- 30106098
TI  - Dexmedetomidine pretreatment inhibits cerebral ischemia/reperfusion-induced
      neuroinflammation via activation of AMPK.
AB  - Focal ischemia/reperfusion (I/R) injury induced cerebral inflammation, aggravates
      brain damage. The aim of the present study was to investigate the protective
      mechanisms of dexmedetomidine (DEX) on I/R brain injury in rats. Sprague-Dawley
      rats were divided to seven experimental groups (18 rats/group): Sham surgery;
      middle cerebral artery occlusion (MCAO) surgery (90 min); DEX10 [10 ug/kg
      intraperitoneal (i.p.) injection 30 min prior to MCAO]; DEX50 (50 ug/kg i.p. 30
      min prior to MCAO); DEX100 (100 ug/kg i.p. 30 min prior to MCAO); DEX50+Yohimbine
      [YOH; 5 mg/kg 10 min prior to DEX (50 ug/kg i.p.) administration and MCAO] and
      YOH (5 mg/kg 40 min prior to MCAO). At 24 h post-MCAO surgery, neurological
      deficit was examined by staining damaged brain tissues with 2,3,5
      triphenyltetrazolium chloride. Neuronal apoptosis in the cerebral cortex was
      histologically assessed by terminal deoxynucleotidyl-transferase-mediated dUTP
      nick end labeling staining, and the expression levels of phosphorylated (p)-AMP
      activated protein kinase (AMPK; Thr172) was detected by western blotting. In
      addition, the expression levels of tumor necrosis factor (TNF)-alpha and
      interleukin (IL)-1beta were assessed by ELISA. At days 1, 2 and 5 following I/R,
      motor functions were assessed by an observer blinded to the study. The brain
      infarct size, neurological deficit scores, number of apoptotic neurons,
      expression levels of pro-inflammatory cytokines TNF-alpha and IL-1beta were
      increased following MCAO, whereas the motor function scores were reduced.
      Pretreatment with DEX prior to MCAO can reverse the effects induced by I/R.
      Compared with rats in the Sham group, the expression levels of p-AMPK were mildly
      increased in the MCAO group and highly increased in the three DEX-treatment
      groups. Pretreatment with YOH reversed the above effects of DEX and produced a
      similar level of cerebral I/R injury. The results demonstrated that precondition
      with DEX exhibited anti-inflammatory effects on brain ischemic injury mediated by
      AMPK signal pathway.

PMID- 30106097
TI  - PDGF-BB promotes the differentiation and proliferation of MC3T3-E1 cells through
      the Src/JAK2 signaling pathway.
AB  - Platelet-derived growth factor-BB (PDGF-BB) serves a critical function in human
      osteoblast differentiation and proliferation. Src and Janus kinase 2 (JAK2) are
      involved in these processes. In our previous study, it was identified that Src
      could promote the phosphorylation of JAK2. However, it has yet to be determined
      whether the Src/JAK2 signaling pathway affects PDGF-BB-mediated osteoblast
      differentiation and proliferation. In the present study, western blotting,
      polymerase chain reaction, alizarin red staining, alkaline phosphatase and Cell
      Counting kit-8 were employed to explore these questions. Firstly, it was
      demonstrated that PDGF-BB activates the Src/JAK2 signaling pathway in MC3T3-E1
      cells in a time-dependent manner. Furthermore, it was demonstrated that PDGF-BB
      expression promoted MC3T3-E1 cell differentiation and proliferation; this process
      was suppressed by AG1295, SU6656 and AG490, which are inhibitors of PDGFR-beta,
      Src and JAK2, respectively. SU6656 downregulated the activity of Src and JAK2,
      while AG490 only downregulated JAK2 activity. Therefore, it was concluded that
      Src is upstream of JAK2. PDGF-BB also upregulated the expression of osteogenesis
      associated genes, and the formation of mineral nodules. However, these effects
      were markedly inhibited by treatment with SU6656. This indicated that PDGF-BB
      promoted MC3T3-E1 cell differentiation and proliferation by activating the
      Src/JAK2 signaling pathway. These results suggested that PDGF-BB may have
      potential applications in the treatment of osteoporosis and bone fractures.

PMID- 30106099
TI  - Overexpression of miR-21 is involved in acute monocytic leukemia-associated
      angiogenesis by targeting IL-12.
AB  - Angiogenesis is important in pathophysiological processes, including the
      pathogenesis of acute monocytic leukemia (AML). MicroRNA-21 (miR-21) is
      overexpressed and exhibits oncogenic activity in cancer. However, the biological
      mechanism underlying the effect of miR-21 in AML remains to be fully elucidated.
      In the present study, the expression levels of miR-21 and vascular endothelial
      growth factor (VEGF) were determined in 26 patients with AML and 28 healthy
      individuals. The secretion of VEGF was also measured following the transfection
      of THP-1 cells with miR-21 mimic or inhibitor. The supernatants of the THP-1
      cells, which were transfected with miR-21 mimic, inhibitor or small interfering
      RNA (si)VEGF, respectively, were used to incubate human umbilical vein
      endothelial cells (HUVECs), following which tube formation of the HUVECs was
      measured. miR-21 targets were predicted using a biological target prediction
      website and confirmed using a luciferase assay. The effects of interleukin (IL)
      12 were investigated by examining the tube formation of HUVECs and the secretion
      of VEGF following recombinant human (rh) IL-12 pretreatment. The results revealed
      that miR-21 and VEGF expression was significantly increased in the peripheral
      blood monocytes of the patients, compared with the healthy controls. There was
      negative correlation between the expression of IL-12 and miR-21 in the serum of
      patients with AML. Furthermore, supernatant VEGF levels from the miR-21 mimic
      transfected THP-1 cells were increased, whereas a decreasing trend was observed
      in the miR-21 inhibitor group. The angiogenic ability of the HUVECs pretreated
      with supernatant from the THP-1 cells transfected with miR-21 mimic was higher,
      and was lower in THP-1 cells co-transfected with miR-21 mimic and siVEGF,
      compared with the miR-21 mimic only group. A luciferase assay demonstrated that
      IL-12 was the direct target of miR-21, and the level of IL-12 in the supernatant
      of THP-1 cells transfected with miR-21 mimic was increased. IL-12 pretreatment
      increased VEGF expression and angiogenic ability in HUVECs. The inactivation of
      miR-21 or activation of its target gene may be a potential therapeutic strategy
      in human AML.

PMID- 30106100
TI  - Investigation of key autophagy-and mitophagy-related proteins and gene expression
      in BALF cells from patients with IPF and RA-ILD.
AB  - Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial
      lung disease with a poor prognosis and limited therapeutic options. Over the past
      decade, research efforts have focused on the pathogenetic mechanisms involved in
      this enigmatic lung disease. Rheumatoid arthritis (RA) is a chronic inflammatory
      autoimmune disease often complicated by the development of interstitial lung
      disease (ILD), leading to high mortality and morbidity. Autophagy is a process
      regulating the turnover of subcellular components and organelles, and represents
      a major cellular homeostatic mechanism. Recent evidence suggests a role of
      autophagy and mitochondrial dysfunction in the development of IPF, focusing on
      lung fibroblasts and epithelial cells. The aim of this study was to examine the
      mRNA levels of molecules involved inthe autophagy pathway in bronchoalveolar
      lavage fluid (BALF)-derived cellsfrom patients with IPF in comparison topatients
      with RA demonstrating lung involvement (ILD) by RT-qPCR. The significant
      upregulation of BECLIN1 was observed in patients with RA-ILD compared with those
      with IPF. Other genes involved in the autophagy pathway were also examined, such
      as Unc-51 like autophagy activating kinase 1 (ULK1), BCL2 interacting protein 3
      (BNIP3) and p62. No differences in the mRNA expression levels of these genes were
      observed. As regards the selective degradation of mitochondria and mitophagy,
      similar PTEN-induced putative kinase 1 (PINK1) and PARKIN; E3 ubiquitin ligase
      (PRKN) expression, as well as PINK1 protein levels, were observed. On the whole,
      the findings of this study demonstrate an increased expression of BECLIN1 in BALF
      cells from patients with RA-ILD compared with those from patients with IPF, while
      similar levels in other key molecules implicating in the autophagy pathway were
      observed in patients with IPF and RA-ILD.

PMID- 30106101
TI  - Oleanolic acid protects against oxidative stress-induced human umbilical vein
      endothelial cell injury by activating AKT/eNOS signaling.
AB  - Oxidative injury of vascular endothelial cells in the initial event of
      atherosclerosis (AS) in diabetes was assessed in the present study. The
      antioxidant effect of oleanolic acid (OA) has attracted much attention. In the
      present study the potential effects of OA on human umbilical vein endothelial
      cells (HUVECs) were investigated. Cell viability was examined using the CCK-8
      assay. The activity of oxidative stress parameters was determined using
      commercial kits. Flow cytometry analysis was performed to detect the level of
      reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and cell
      apoptosis. The expression levels of target genes and proteins were examined by
      reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and
      western blot analysis. It was indicated that cell viability that was suppressed
      by high glucose was increased by the pretreatment of OA, and nitric oxide (NO)
      generation, the activities of superoxide dismutase (SOD) and catalase (CAT) were
      recovered by OA. By contrast, it was observed that OA decreased the MDA content.
      Notably, the pretreatment of OA alleviated mitochondria damage by reducing the
      level of ROS and maintaining MMP. In addition, apoptosis that was caused by high
      glucose was reduced by OA. Pro-apoptotic genes (caspase-3, Fas, Fasl) and anti
      apoptotic gene (Bcl-2) expression levels were decreased and increased in the OA
      groups, respectively. Furthermore, the activity of AKT/endothelial nitric oxide
      synthase (eNOS) signaling was elevated by OA. Taken together, it was suggested
      that OA could protect against oxidative stress-induced apoptosis of HUVECs, which
      was associated with AKT/eNOS signaling pathway.

PMID- 30106103
TI  - Antifibrotic potential of bone marrow-derived mesenchymal stem cells in biliary
      atresia mice.
AB  - Biliary atresia (BA) is a rare and severe disease that affects infants where a
      fibroinflammatory process destroys the bile ducts, leading to fibrosis and
      biliary cirrhosis, and mortality if untreated. Bone marrow-derived mesenchymal
      stem cells (BMMSCs) have been considered as a promising therapy in fibrotic
      diseases. The aim of the present was to investigate the anti-fibrotic roles of
      BMMSC transplantation in a BA mouse model. Mouse BA models were established by
      Rhesus rotavirus administration to neonatal mice. The results revealed that the
      liver enzyme and bilirubin metabolism levels, and the levels of the oxidative
      stress marker malondialdehyde (MDA) and the fibrosis marker were all increased in
      the BA model, while the liver tissue levels of superoxide dismutase and
      glutathione peroxidase were reduced. The hematoxylin and eosin and Masson's
      trichrome staining revealed severe liver fibrosis and collagen accumulation in BA
      livers. However, these indicators were all reversed once the BA mice were
      administered the BMMSC inoculation. In conclusion, the present study demonstrated
      the anti-fibrotic potential of BMMSCs in BA mice, which may provide a novel
      approach to ameliorate the fibrotic response in BA patients.

PMID- 30106102
TI  - EGFR may participate in immune evasion through regulation of B7-H5 expression in
      non-small cell lung carcinoma.
AB  - Lung cancer is one of the most prevalent malignancies worldwide; it has been
      ranked the most lethal type of cancer. Non-small cell lung carcinoma (NSCLC)
      comprises >80% of all types of lung cancer. Although certain achievements have
      been made in the treatment of NSCLC, including the targeted gene drug epidermal
      growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), the five-year
      survival rate of patients has not significantly increased. A previous study
      demonstrated that B7-H5, a novel co-stimulatory molecule in the B7 molecule
      family, was negatively correlated with EGFR in pancreatic cancer. Thus, in the
      present study, we aimed to investigate whether EGFR participates in immune
      evasion, probably through regulation of B7-H5 expression. NCI-H1299 NSCLCL cells
      were divided into control, mock, small interfering-EGFR and EGFR-TKI groups. The
      cell viability and apoptosis rate were analysed by a Cell Counting Kit-8 assay
      and flow cytometry. The transforming growth factor (TGF)-beta and interleukin
      (IL)-10 content was measured using an ELISA. The expression levels of EGFR, B7
      H5, Survivin, apoptosis regulator Bax, apoptosis regulator Bcl-2 (Bcl-2), TGF
      beta, vascular endothelial growth factor (VEGF), IL-10 and cyclooxygenase (COX)-2
      were assessed via quantitative PCR and western blotting. The activation of the
      tyrosine-protein kinase JAK2 (JAK2)/signal transducer and activator of
      transcription 3 (STAT3) signalling pathway was detected using western blotting.
      The results demonstrated a notable negative correlation between EGFR and B7-H5
      expression levels in cancer tissues and cell lines. Inhibition of EGFR expression
      via gene silencing and EGFR inhibition markedly decreased cell viability and
      increased the apoptosis of NCI-H1299 cells, by upregulating survivin and Bcl-2
      expression. The protein expression levels of TGF-beta, VEGF, IL-10 and COX-2 were
      additionally decreased, with weak activation of the JAK2/STAT3 signalling
      pathway. EGFR may be involved in immune evasion, possibly through regulation of
      B7-H5 expression in NSCLC.

PMID- 30106105
TI  - Identification of genes and genetic networks associated with BAG3-dependent cell
      proliferation and cell survival in human cervical cancer HeLa cells.
AB  - Bcl-2-associated athanogene (BAG) 3, is a member of the BAG protein family and a
      known co-chaperone of heat shock protein (HSP) 70. BAG3 serves a role in
      regulating a variety of cellular functions, including cell growth, proliferation
      and cell death including apoptosis. BAG3 is a stress-inducible protein, however
      the constitutive expression level of BAG3 is increased in cancer cells compared
      with healthy cells. Recent proteomics technology combined with bioinformatics has
      revealed that BAG3 participates in an interactome with a number of proteins other
      than its typical partner HSP70. The functional types represented in the
      interactome included nucleic acid binding proteins and transcription factors, as
      well as chaperones, which indicated that overexpression of BAG3 may contribute to
      proliferation and cell survival through the alteration of gene transcription.
      While an increasing number of studies have addressed the function of BAG3 as a co
      chaperone protein, BAG3-dependent alteration of gene transcription has not been
      studied extensively. The present study established two BAG3 knockout human
      cervical cancer HeLa cell clones and addressed the role of BAG3 in cell
      proliferation and survival through gene transcription, using DNA microarray-based
      transcriptome analysis and bioinformatics. The present study also identified two
      genetic networks associated with 'cellular growth and proliferation' and 'cell
      death and survival', which are dysregulated in the absence of BAG3, and may
      therefore be linked to BAG3 overexpression in cancer. These findings provide a
      molecular basis for understanding of BAG3-dependent cell proliferation and
      survival from the aspect of alteration of gene expression.

PMID- 30106104
TI  - In vitro and in vivo study of the expression of the Syk/Ras/c-Fos pathway in
      chronic glomerulonephritis.
AB  - Chronic glomerulonephritis (CGN) is the most common form of glomerular disease;
      however, its associated molecular mechanisms remain unclear. Spleen tyrosine
      kinase (Syk) is a key mediator of B-receptor signaling on the surface of
      inflammatory cells. The primary target for R406 is Syk. The aim of the present
      study was to investigate the molecular mechanisms involved in a rat model of CGN
      induced by adriamycin (ADR) and in the rat glomerular mesangial cell line, HBZY
      1, stimulated by lipopolysaccharide (LPS). CGN was induced in the rat models by
      two intravenous injections of ADR into the tail: 3.5 mg/kg ADR was given on the
      first day and 3.0 mg/kg on the fourteenth day. HBZY-1 cells were incubated with
      0.5 ug/ml LPS for 48 h. The pathological alterations in the kidney tissues were
      observed by hematoxylin and eosin staining. The 24 h urinary protein, blood urea
      nitrogen (BUN) and creatinine levels were measured using an automatic
      biochemistry analyzer. The mRNA expression levels of Syk, Ras, mitogen activated
      protein kinase kinase (MEK), extracellular signal regulated kinase (ERK)1/2 and c
      Fos was measured by reverse transcription-quantitative polymerase chain reaction.
      Subsequently, the protein levels of phosphorylated (p)-Syk, Ras, p-MEK1/2, p
      ERK1/2 and c-Fos were measured by western blot analysis. In the model group, 24 h
      urinary protein, BUN and creatinine levels were increased when compared with the
      normal group (P<0.05). In addition, compared with the normal group, the mRNA and
      protein levels of the Syk/Ras/c-Fos pathway components in vitro and in vivo were
      markedly increased, inhibiting the abnormal cell viability of mesangial cells. In
      conclusion, the results of the present study suggested a potential role for the
      Syk/Ras/c-Fos signaling pathway in CGN, which indicated the necessity for further
      investigation at the clinical level.

PMID- 30106106
TI  - Cellular and molecular changes to chondrocytes in an in vitro model of
      developmental dysplasia of the hip-an experimental model of DDH with swaddling
      position.
AB  - The aim of the present study was to assess the cellular and molecular changes to
      chondrocytes in a developmental dysplasia of the hip (DDH) model and to
      investigate the early metabolism of chondrocytes in DDH. Neonatal Wistar rats
      were used for the DDH model with swaddling position. Primary cultures of
      chondrocytes were prepared at serial interval stages (2, 4, 6 and 8 weeks) to
      investigate cellular proliferation. The expression of collagen II and aggrecan
      mRNA was detected to assess the anabolic ability of chondrocytes. The expression
      of matrix metallopeptidase (MMP)-13 and ADAM metallopeptidase with thrombospondin
      type 1 motif 5 (ADAMTS-5) mRNA was measured to investigate the degradation of
      collagen II and aggrecan, respectively. Morphological changes were observed in
      coronal dissection samples after the removal of fixation. Primary chondrocytes at
      serial intervals were assessed using a Cell Counting Kit-8 assay and the results
      revealed that DDH chondrocytes had more proliferative activity. The expression of
      collagen II mRNA was upregulated at 2 weeks and was more sensitive to mechanical
      loading compared with aggrecan. Similar changes occurred at 6 weeks. Furthermore,
      MMP-13 and ADAMTS-5 mRNA expression levels were upregulated at 2 weeks. It was
      also demonstrated that DDH chondrocytes exhibited high proliferative activity at
      the early stages and degeneration later.

PMID- 30106108
TI  - Effects of leptin on neurocognitive and motor functions in juvenile rats in a
      preterm brain damage model.
AB  - Preterm infants face lifelong disabilities, including learning disorders, as well
      as visual, auditory and behavioral problems. Recent studies have demonstrated
      that leptin, an adipocytokine encoded by a gene associated with obesity and
      expressed in adipose tissue, affects neurocognitive and motor function; however,
      the mechanisms of brain damage in preterm infants are unclear. In the present
      study, the neuroprotective effects of leptin in a rat model of preterm hypoxic
      ischemic brain damage were investigated. Rats (2-days-old) were subjected to
      brain damage (ligation of the common carotid artery followed by exposure to 6%
      oxygen for 2 h) and treated with vehicle (control) or leptin. Spatial memory was
      analyzed in the present study using the Morris water maze test 19 days following
      ligation. Over the 24-day post-surgical observation period, capture-resistance
      test, forelimb suspension and open field tests were conducted to evaluate motor
      function and anxiety-associated behavior. Treatment with leptin did not affect
      survival rate or body weight. Treatment with leptin increased the number of
      platform crossings in rats with premature brain damage in the Morris water maze
      test, which was used to assess spatial memory. Multivariate analysis revealed
      that leptin reduced the latency to finding the platform location, independent of
      gender and weight. In the capture-resistance, forelimb suspension and open field
      tests, there were no differences between animals administered leptin and the sham
      group. Collectively, the results of the present study suggested that leptin may
      alleviate spatial memory impairment resulting from premature brain damage,
      independent of gender or weight. These results may improve understanding of the
      neuroprotective effects exhibited by leptin in infants with preterm brain damage.

PMID- 30106107
TI  - Ghrelin improves pilocarpine-induced cerebral cortex inflammation in epileptic
      rats by inhibiting NF-kappaB and TNF-alpha.
AB  - Ghrelin has a protective function in the nervous system, including anti
      inflammatory and antiapoptotic. The objective of the present study was to examine
      the anti-inflammatory effects of the ghrelin on nuclear factor-kappaB (NF-kappaB)
      and tumor necrosis factor-alpha (TNF-alpha) gene and protein expression in an
      epileptic seizure model. Epileptic seizures were induced in healthy male Wistar
      rats (~3 weeks old) with 300 mg/kg pilocarpine, and brains from rats with Racine
      stage IV or V seizures were investigated further in the present study. The effect
      of ghrelin treatment on TNF-alpha and NF-kappaB protein and mRNA expression was
      assessed by immunohistochemistry and semi-quantitative reverse transcription
      polymerase chain reaction, respectively. TNF-alpha and NF-kappaB protein and mRNA
      expression were significantly increased in the pilocarpine and the pilocarpine +
      saline groups compared with the control group. Ghrelin intervention significantly
      decreased TNF-alpha and NF-kappaB protein and mRNA expression compared with the
      pilocarpine and the pilocarpine + saline groups, although it did not reduce
      expression levels to those seen in the normal control group. Ghrelin reduces
      inflammation in cortical neurons following epileptic seizure, and therefore may
      reduce necrosis and the loss of nerve cells, preserving the normal function of
      the cortex. Ghrelin may alleviate cortex inflammation reaction by adjusting the
      TNF-alpha and NF-kappaB so as to reduce child epilepsy attack repeatedly. The
      findings of the present study may contribute to the clarification of the role of
      Ghrelin in the brain in seizure-induced immune system physiology and may also
      present novel approaches to the etiology and treatment of epileptic seizures.

PMID- 30106109
TI  - miR-454-3p suppresses cell migration and invasion by targeting CPEB1 in human
      glioblastoma.
AB  - MicroRNAs (miRNA/miRs) serve crucial roles in the progression of human
      glioblastoma (GBM); however, the exact regulatory mechanisms of miRNAs in human
      GBM remain unclear. The present study aimed to investigate the roles of miR-454
      3p in human GBM. Reverse transcription-quantitative polymerase chain reaction (RT
      qPCR) analysis was performed to examine the expression of miR-454-3p in glioma
      tissues and adjacent tissues. Human GBM cell lines (LN-229, A172 and GL15) and a
      normal human astrocyte cells (HA1800) were used for analysis. In addition, RT
      qPCR and western blotting were applied for mRNA and protein expression analysis,
      respectively. The cell proliferation was measured using a Cell Counting kit-8
      assay. Furthermore, scratch and Transwell assays were employed for the analysis
      of cell migration and invasion. A luciferase reporter assay was used to verify
      the target of miR-454-3p. The results revealed that miR-454-3p was downregulated
      in the glioma tissues and GBM cell lines, including LN-229, A172 and GL15.
      Additionally, the overexpression of miR-454-3p significantly suppressed the
      proliferation, migration and invasion of LN-229 cells. Furthermore, cytoplasmic
      polyadenylation element-binding protein 1 (CPEB1) was confirmed as a direct
      target of miR-454-3p. These findings indicated that the overexpression of miR-454
      3p inhibited cell proliferation, migration and invasion by downregulating CPEB1.
      Therefore, miR-454-3p may act as a tumor suppressor and represent an effective
      therapeutic strategy in GBM.

PMID- 30106110
TI  - Silencing of PYGB suppresses growth and promotes the apoptosis of prostate cancer
      cells via the NF-kappaB/Nrf2 signaling pathway.
AB  - Brain-type glycogen phosphorylase (PYGB) is an enzyme that metabolizes glycogen,
      whose function is to provide energy for an organism in an emergency state. The
      present study purposed to investigate the role and mechanism of PYGB silencing on
      the growth and apoptosis of prostate cancer cells. A cell counting kit-8 assay
      and flow cytometry were performed to determine the cell viability, apoptosis and
      reactive oxygen species (ROS) content, respectively. Colorimetry was performed to
      analyze the activity of caspase-3. Western blotting and reverse transcription
      quantitative polymerase chain reaction were used to evaluate the associated mRNA
      and protein expression levels. The results revealed that PYGB was upregulated in
      prostate cancer tissues and was associated with disease progression. In addition,
      PYGB silencing suppressed the cell viability of PC3 cells. PYGB silencing
      promoted apoptosis of PC3 cells via the regulation of the expression levels of
      cleaved-poly (adenosine diphosphate-ribose) polymerase, cleaved-caspase-3, B-cell
      lymphoma-2 (Bcl-2) and Bcl-2-associated X protein. PYGB silencing increased the
      ROS content in PC3 cells, and affected nuclear factor (NF)-kappaB/nuclear factor
      erythroid 2-related factor 2 (Nrf2) signaling pathways in PC3 cells. In
      conclusion, PYGB silencing suppressed the growth and promoted the apoptosis of
      prostate cancer cells by affecting the NF-kappaB/Nrf2 signaling pathway. The
      present study provided evidence that may lead to the development of a potential
      therapeutic strategy for prostate cancer.

PMID- 30106112
TI  - Therapeutic potential of hyaluronic acid/chitosan nanoparticles for the delivery
      of curcuminoid in knee osteoarthritis and an in vitro evaluation in chondrocytes.
AB  - Knee osteoarthritis (OA) is the main cause of leg pain in middle-aged and elderly
      individuals. Hyaluronic acid (HA), as well as curcuminoid, has been used in the
      treatment of knee OA. In the present study, HA/chitosan nanoparticles (CNPs) were
      prepared for the delivery of curcuminoid, in order to investigate whether HA and
      curcuminoid can act synergistically as a better treatment option. The knee OA
      model was established by the Hulth method, and a knee OA chondrocyte model was
      constructed by the co-induction of interleukin-1beta and tumor necrosis factor
      (TNF)-alpha. The drug loading capacity of HA/CNP for the delivery of curcuminoid
      was measured by an ultraviolet assay, and the cytotoxicity to chondrocytes was
      measured by an MTT assay. Collagen II was detected by immunofluorescence, and the
      expression levels of nuclear factor (NF)-kappaB and inflammation-related genes in
      cartilage tissue and chondrocytes were detected. Chondrocyte proliferation was
      determined by an EdU assay, and chondrocyte apoptosis was determined by flow
      cytometry. The Mankin pathological score of the Outerbridge classification was
      obtained. The results demonstrated that the optimum drug loading capacity of
      HA/CNP for the delivery of curcuminoid was 38.44%, with a good sustained release
      function. HA/CNP treatment resulted in inhibition of the NF-kappaB pathway, as
      well as the expression of matrix metalloproteinase (MMP)-1 and MMP-13, but it
      increased collagen II expression. HA/CNP for the delivery of curcuminoid
      significantly decreased the Outerbridge classification and Mankin pathological
      scores to close to normal until the 4th week. Furthermore, it was also observed
      that all the effects of HA/CNP on the delivery of curcuminoid were more prominent
      compared with the effects of HA or curcuminoid treatment individually. Taken
      together, these findings demonstrated that HA/CNP for the delivery of curcuminoid
      may suppress inflammation and chondrocyte apoptosis in knee OA via repression of
      the NF-kappaB pathway.

PMID- 30106111
TI  - Sulforaphane protects rabbit corneas against oxidative stress injury in
      keratoconus through activation of the Nrf-2/HO-1 antioxidant pathway.
AB  - The aim of the present study was to examine whether activation of the nuclear
      factor E2-related factor 2 (Nrf-2)/heme oxygenase-1 (HO-1) antioxidant pathway in
      the cornea was involved in the protective effect of sulforaphane (SF) following
      keratoconus (KC) injury. Following epithelial debridement, collagenase type II
      was applied in KC groups at room temperature for 30 min. Following this, rabbits
      were administered with a subconjunctival (s.c.) injection of SF or placebo (maize
      oil) daily for a total of 2 weeks. To investigate whether HO-1 was involved in
      the Nrf-2-related antioxidant pathway, rabbits were injected with zinc (II)
      protoporphyrin IX (ZnPP IX, s.c.) treatment in combination with SF 24 h following
      the application of collagenase type II. The protective effects of SF were
      evaluated by examining the mean keratometry (Km) and central cornea thickness
      (CCT), measuring reactive oxygen species (ROS) production using immunofluorescent
      staining, and analyzing the protein expression of NADPH oxidase (Nox) family
      members Nox-2 and Nox-4, and Nrf-2 and HO-1 using immunohistochemistry and
      western blot analysis. The mRNA levels of Nox-2, Nox-4, Nrf-2 and HO-1 were
      quantitatively detected by reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) analysis. No significant difference in Km or CCT was observed
      among groups prior to surgery (P=0.700 and P=0.982, respectively). KC induced an
      apparent increase of ROS generation, and caused a significant increase in Km and
      a significant decrease in CCT. These changes were neutralized or reversed by SF
      treatment. Simultaneously, SF treatment decreased the expression of Nox-2 and Nox
      4, and enhanced the expression of Nrf-2 and HO-1 in the KC corneas. The RT-qPCR
      results indicated that SF induced downregulation of the mRNA expression of Nox-2
      and Nox-4, and upregulation of the mRNA expression of Nrf-2 and HO-1 following KC
      injury. The HO-1 inhibitor, ZnPP IX, counteracted the protective effects of SF on
      KC corneas. Therefore, the present study provided evidence that activation of the
      Nrf-2/HO-1 signal transduction pathway may partially promote the protective
      effect of the antioxidant SF in the KC cornea.

PMID- 30106113
TI  - Differential miRNAomics of the synovial membrane in knee osteoarthritis induced
      by bilateral anterior cruciate ligament transection in rats.
AB  - The differential microRNA (miRNA) omics of the synovial membrane were
      investigated using a rat model of knee osteoarthritis (KOA) induced by bilateral
      anterior cruciate ligament transection, which produced pathological biomarkers in
      KOA. Sprague-Dawley rats were randomly divided into two groups; Sham-operated and
      KOA-operated group. The KOA rats were subjected to bilateral anterior cruciate
      ligament transection. After 6 weeks, total RNA was extracted from the knee joint
      synovial membrane of the rats and a microRNA (miR) microarray was performed to
      identify differentially expressed miRs. Subsequently, the obtained differentially
      expressed miRs were validated by reverse transcription-quantitative polymerase
      chain reaction (RT-qPCR) analysis. A total of 24 miRs were identified with
      alterations >=1.5-fold in the synovial membrane in the KOA-operated group
      compared with the sham-operated group, of which 4 miRs (miR-532-5p, -200b-5p, 
      377-3p and -759-5p) were decreased and 20 miRs (miR-382-3p, -223-3p, -100-5p, 
      30d-5p, -183-5p, -130, -92b-3p, -125b-3p, -151-3p, -155-3p, 27a-3p, -146b-3p, 
      885-5p, -352, -184, -345-5p, -30a-5p and -9a-5p) were increased. Subsequently, RT
      qPCR was used to validate the expressions of miR-223, -100, -345, -130, -382, 
      377, -352, -200b, -9a and -183, which were upregulated by a fold change of >=1.5
      in synovial membranes of KOA rats compared with shams. Furthermore, in vitro miR
      223 mimic could suppress the luciferase activity of NACHT, LRR and PYD domains
      containing protein 3 (NLRP3) 3' untranslated region by detecting of dual
      luciferase reporter vector. Additionally, the expression of NLRP3, interleukin
      (IL)-1beta and IL-18 significantly increased in the synovial membrane of KOA
      rats. A total of 24 different miRs were determined by comparing the miRNAomics in
      the synovial membrane of the KOA model rats. Furthermore, the miR-233-regulated
      NLRP3 inflammasome was implicated in synovial membrane injury, which may be an
      important mechanism of KOA pathogenesis.

PMID- 30106114
TI  - miR-197 promotes the invasion and migration of colorectal cancer by targeting
      insulin-like growth factor-binding protein 3.
AB  - The incidence and mortality of colorectal cancer (CRC) have been rising rapidly
      in China. A number of miRNAs have been confirmed to be involved in diverse
      biological processes of CRC. However, whether miR-197 plays a role in migration
      and invasion of CRC has never been explored. In the present study Transwell
      chambers were used in in vitro migration and invasion assays. Dual-luciferase
      reporter assay was employed to confirm the target of miR-197. RT-PCR and IHC
      staining were performed to quantify miR-197 and IGFBP3 expression, respectively.
      Clinicopathological features were collected for statistical analysis. We observed
      that the overexpression of miR-197 significantly promoted migration and invasion
      in 3 CRC cell lines including HCT8, HCT116 and SW480 (P<0.05), while the
      inhibition of miR-197 weakened both biological processes (P<0.05). In
      bioinformatics and dual-luciferase reporter assay, luciferase activities of
      IGFBP3-WT-transfected cells significantly decreased upon miR-197 overexpression
      and this inhibitory effect was abolished when miR-197 binding region in IGFBP3 3'
      UTR was mutated, which indicated that miR-197 directly suppressed the expression
      of IGFBP3 in CRC cells by targeting its 3'UTR. Downregulation of the expression
      of IGFBP3 by using targeted siRNA led to significant enhancement of cell
      migration and invasion in two CRC cell lines including HCT8 and HCT116 (P<0.05).
      Finally, in cancerous tissues of CRC patients, the miR-197 level was inversely
      correlated with the expression of IGFBP3 (P=0.026), which indicated that miR-197
      may modulate cell migration and invasion by targeting IGFBP3 in CRC patients. In
      conclusion, we revealed that miR-197 modulates IGFBP3 and therefore plays a
      critical role in regulating CRC migration and invasion.

PMID- 30106115
TI  - Identification of LINC01279 as a cell cycle-associated long non-coding RNA in
      endometriosis with GBA analysis.
AB  - Endometriosis affects 6-10% of women of reproductive age. Though a significant
      amount of research has explored the pathogenesis of endometriosis, little is
      clear. Elucidating the mechanisms is urgently required for improving the
      therapeutic efficiency of endometriosis treatment. Long non-coding RNAs (lncRNAs)
      have recently acquired extensive attention as regulatory components in a variety
      of biological processes and diseases. However, the functions of many lncRNAs in
      endometriosis are poorly understood. Therefore, the exploration of the
      dysregulated genes in endometriosis, particularly lncRNAs, is of importance. In
      the present study, datasets for endometriosis, including GSE7305, GSE7846,
      GSE29981 and E-MTAB-694, were downloaded from Gene Expression Omnibus and
      ArrayExpress. Then, the limma and Affy packages were used to analyze the CEL
      file. The RankProd method was used to conduct meta-analysis. Long intergenic non
      protein coding RNA 1279 (LINC01279) was significantly upregulated in the three
      datasets, and was the most upregulated lncRNA as determined by the RankProd
      method. Gene set enrichment and Gene Ontology analyses were conducted, which
      revealed that LINC01279 is likely to function as a cell cycle mediator in
      endometriosis. Finally, it was identified that LINC01279 is strongly associated
      with certain previously identified key factors in the development of
      endometriosis, including cyclin-dependent kinase 14 and C-X-C motif chemokine
      ligand 12. Thus, it was demonstrated that LINC01279 may be associated with the
      pathogenesis of endometriosis. This may potentially represent a target in the
      therapy of endometriosis.

PMID- 30106116
TI  - Epigallocatechin-3-gallate affects the proliferation, apoptosis, migration and
      invasion of tongue squamous cell carcinoma through the hippo-TAZ signaling
      pathway.
AB  - The purpose of the present study was to investigate the mechanism by which
      epigallocatechin-3-gallate (EGCG) inhibits the biological behaviors of the tongue
      squamous cell carcinoma (TSCC) through the Hippo-tafazzin (TAZ) signaling pathway
      and to provide insights into molecular targeted therapy in TSCC. CAL27 and SCC15
      cells were treated with different concentrations of EGCG for 24 h. Cell
      proliferation was determined using Cell-Counting Kit-8 and EdU assays. Cell
      apoptosis was evaluated by flow cytometry. Cell migration and invasion were
      measured using scratch and Transwell assays, respectively. Furthermore, protein
      levels of associated target genes were detected using a western blot assay. It
      was demonstrated that EGCG affected biological behaviors of CAL27 and SCC15 cells
      in concentration- and time-dependent manners. In addition, EGCG decreased the
      protein levels of TAZ, LATS1, MOB1 and JNK. Overexpression of TAZ alleviated the
      effect of EGCG on CAL27 cells. Furthermore, the combination of EGCG and
      simvastatin inhibited the proliferation, migration and invasion, and promoted
      apoptosis significantly compared with single treatment in CAL27 cells. The
      results of the present study suggested that EGCG affects proliferation,
      apoptosis, migration and invasion of TSCC through the Hippo-TAZ signaling
      pathway.

PMID- 30106118
TI  - MicroRNA-152 regulates insulin secretion and pancreatic beta cell proliferation
      by targeting PI3Kalpha.
AB  - An increasing number of microRNAs (miRNAs/miRs) are reported to have important
      roles in diabetes. Glucose-stimulated insulin secretion and pancreatic beta cell
      proliferation are essential in the control of metabolic disorder, however, the
      underlying molecular mechanisms remain unclear. The present study investigated
      the function of miR-152 in diabetes. The results of reverse transcription
      quantitative polymerase chain reaction demonstrated that miR-152 levels in the
      blood were markedly reduced in patients with diabetes compared with nondiabetic
      controls. In addition, a high blood glucose concentration was significantly
      associated with reduced miR-152 expression. Furthermore, overexpression of miR
      152 using miR-152 mimics promoted the proliferation of INS-1 and MIN6 cells, as
      determined by an MTT assay, in addition to insulin secretion, while knockdown of
      miR-152 using an inhibitor led to the opposite effects. Phosphatidylinositol 3
      kinase (PI3K) signaling has been reported to inhibit insulin secretion, however,
      the regulation of PI3K in the pancreatic beta cell is poorly understood. The
      present study identified that PI3K catalytic subunit alpha (PI3Kalpha) was a
      direct target gene of miR-152 using a luciferase reporter assay, and miR-152
      inhibited the expression of PI3Kalpha at the protein level, which was determined
      by western blotting. Therefore, the regulation of insulin secretion and
      pancreatic beta cell proliferation may occur via the miR-152/PI3Kalpha axis. The
      overexpression of PI3Kalpha in INS-1 and MIN6 cells partially reduced the effects
      of miR-152 overexpression on insulin secretion. Consistently, PI3Kalpha levels
      were reduced in murine pancreatic islets following treatment with 20 mM glucose,
      and increased in blood samples from patients with diabetes compared with healthy
      individuals. In conclusion, the results of the present study demonstrate that miR
      152 may have an important role in pancreatic beta cell function, and established
      an association between miR-152 and the PI3Kalpha axis. Therefore, targeting
      PI3Kalpha may be a potential therapeutic option for diabetes.

PMID- 30106117
TI  - Establishment of a SVM classifier to predict recurrence of ovarian cancer.
AB  - Gene expression data using retrieved ovarian cancer (OC) samples were used to
      identify genes of interest and a support vector machine (SVM) classifier was
      subsequently established to predict the recurrence of OC. Three datasets
      (GSE17260, GSE44104 and GSE51088) investigating OC gene expression were
      downloaded from the Gene Expression Omnibus. Differentially expressed genes
      (DEGs) in samples from patients with non-recurrent and recurrent OC were revealed
      via a homogeneity test and quality control analysis. A protein-protein
      interaction (PPI) network was subsequently established for the DEGs using data
      from Biological General Repository for Interaction Datasets, Human Protein
      Reference Database and Database of Interacting Proteins. Degrees of interaction
      and betweenness centrality (BC) scores were calculated for each node in the PPI
      network. The top 100 genes ranked by BC scores were selected to identify feature
      genes via recursive feature elimination using the GSE17260 dataset. Following
      this, a SVM classifier was constructed and further validated using the GSE44104
      and GSE51088 datasets and independent gene expression data obtained from the
      Cancer Genome Atlas (TCGA). A total of 639 DEGs were identified from the three
      gene expression datasets, and a PPI network including 249 nodes and 354 edges was
      constructed. A SVM classifier consisting of 39 feature genes (including cullin 3,
      mouse double minute 2 homolog, aurora kinase A, WW domain containing
      oxidoreducatase, large tumor suppressor kinase 2, sirtuin 6, staphylococcal
      nuclease and tudor domain containing 1, leucine rich repeats and immunoglobulin
      like domains 1 and aurora kinase 1 interacting protein 1) was subsequently
      constructed. The prediction accuracies of the SVM classifier for GSE17260,
      GSE44104 and GSE51088 datasets as well as data downloaded from TCGA were revealed
      to be 92.7, 93.3, 96.6 and 90.4%, respectively. Furthermore, the results of the
      present study revealed that patients with predicted non-recurrent OC survived
      significantly longer compared with the patients with predicted recurrent OC
      (P=6.598x10-6). A SVM classifier consisting of 39 feature genes was established
      for predicting the recurrence and prognosis of OC. Therefore, the results of the
      present study suggested that the 39 feature genes may serve important roles in
      the development of OC and may represent therapeutic biomarkers of OC.

PMID- 30106119
TI  - Absence of Sirt3 aggravates cisplatin nephrotoxicity via enhanced renal tubular
      apoptosis and inflammation.
AB  - Cisplatin-based chemotherapy is commonly used in the treatment of solid tumors;
      however, this agent is limited by its adverse effects on normal tissues,
      including the kidneys, ears and peripheral nerves. Mechanisms of cisplatin
      nephrotoxicity are proposed to involve oxidative stress, inflammation, cellular
      apoptosis and cell cycle regulation. Sirtuin 3 (Sirt3) is a member of the sirtuin
      family of NAD+-dependent enzymes with homology to Saccharomyces cerevisiae gene
      silent information regulator 2. Sirt3 is located in mitochondria and is involved
      in mitochondrial energy metabolism and function; however, the role of Sirt3 in
      cisplatin nephrotoxicity remains unclear. In the present study, whether Sirt3 has
      anti-inflammatory and anti-apoptotic effects on cisplatin-induced nephrotoxicity
      was investigated in mice. Sirt3 knockout mice (Sirt3(-/-)) and corresponding wild
      type mice were employed in the present study. Cisplatin nephrotoxicity was
      induced by intraperitoneal injection of cisplatin (20 mg/kg). After 3 days
      following cisplatin treatment, blood and kidney tissues were harvested. Renal
      function and histology were evaluated. Tubular apoptosis, cell adhesion molecule
      expression, and inflammatory cells were evaluated by immunohistochemistry and
      western blot analysis. Following the induction of cisplatin nephrotoxicity, renal
      function was significantly aggravated in Sirt3 knockout (KO) mice. Tubular injury
      and inflammatory cell infiltration were significantly increased in Sirt3KO mice
      compared with wild type mice. Terminal deoxynucleotidyl transferase-mediated dUTP
      nick-end label-positive tubular cells and renal monocyte chemoattractant protein
      1 expression levels were increased in Sirt3KO mice compared with in wild type
      mice. In summary, the absence of Sirt3 aggravated in renal injury by increasing
      renal inflammation and tubular apoptosis. The results of the present study
      suggested that Sirt3 may have an important role in cisplatin-induced
      nephrotoxicity.

PMID- 30106120
TI  - Tetraspanin family identified as the central genes detected in gastric cancer
      using bioinformatics analysis.
AB  - Gastric cancer has become a serious disease in the past decade. It has the second
      highest mortality rate among the four most common cancer types, leading to
      ~700,000 mortalities annually. Previous studies have attempted to elucidate the
      underlying biological mechanisms of gastric cancer. The present study aimed to
      obtain useful biomarkers and to improve the understanding of gastric cancer
      mechanisms at the genetic level. The present study used bioinformatics analysis
      to identify 1,829 differentially expressed genes (DEGs) which were obtained from
      the GSE54129 dataset. Using protein-protein interaction information from the
      Search Tool for the Retrieval of Interacting Genes database, disease modules were
      constructed for gastric cancer using Cytoscape software. In the Gene Ontology
      analysis of biology processes, upregulated genes were significantly enriched in
      'extracellular matrix organization', 'cell adhesion' and 'inflammatory response',
      whereas downregulated DEGs were significantly enriched in 'xenobiotic metabolic
      process', 'oxidation-reduction process' and 'steroid metabolic process'. During
      Kyoto Encyclopedia of Genes and Genomes analysis, upregulated DEGs were
      significantly enriched in 'extracellular matrix-receptor interaction', 'focal
      adhesion' and 'PI3K-Akt signaling pathway', whereas the downregulated DEGs were
      significantly enriched in 'chemical carcinogenesis', 'metabolism of xenobiotics
      by cytochrome P450' and 'peroxisome'. The present study additionally identified
      10 hub genes from the DEGs: Tumor protein p53 (TP53), C-X-C motif chemokine
      ligand 8 (CXCL8), tetraspanin 4 (TSPAN4), lysophosphatidic acid receptor 2
      (LPAR2), adenylate cyclase 3 (ADCY3), phosphoinositide-3-kinase regulatory
      subunit 1 (PIK3R1), neuromedin U (NMU), C-X-C motif chemokine ligand (CXCL12),
      fos proto-oncogene, AP-1 transcription factor subunit (FOS) and sphingosine-1
      phosphate receptor 1 (S1PR1), which have high degrees with other DEGs. The
      survival analysis revealed that the high expression of ADCY3, LPAR2, S1PR1, TP53
      and TSPAN4 was associated with a lower survival rate, whereas high expression of
      CXCL8, FOS, NMU and PIK3R1 was associated with a higher survival rate. No
      significant association was identified between CXCL12 and survival rate.
      Additionally, TSPAN1 and TSPAN8 appeared in the top 100 DEGs. Finally, it was
      observed that 4 hub genes were highly expressed in gastric cancer tissue compared
      with para-carcinoma tissue in the 12 patients; the increased TSPAN4 was
      significant (>5-fold). Tetraspanin family genes may be novel biomarkers of
      gastric cancer. The findings of the present study may improve the understanding
      of the molecular mechanisms underlying the development of gastric cancer.

PMID- 30106122
TI  - Cryptotanshinone inhibits cellular proliferation of human lung cancer cells
      through downregulation ofIGF-1R/PI3K/Akt signaling pathway.
AB  - Lung cancer is one of the most commonly diagnosed malignancies worldwide.
      Cryptotanshinone (CPT) is a diterpene quinone compound extracted from natural
      plants and has been reported to have anticancer effects in several cancers
      including human lung cancer. However, the mechanism by which CPT acts to prevent
      lung cancer cell growth is largely unknown. In the present study, by using MTT
      assay, colony formation assay, wound healing and western blotting assays, the
      effects of CPT on the cell proliferation and migration of human lung cancer cells
      and the potential cellular signaling mechanisms were investigated. The data
      demonstrated that CPT exhibited anti-proliferative effects against A549 and H1299
      cells. In parallel, the migration of A549 cells was also markedly inhibited by
      CPT treatment. Further study indicated that CPT not only inhibited the basal
      phosphorylation level of insulin-like growth factor 1 receptor (IGF-1R) and RAC
      alpha serine/threonine-protein kinase (Akt), but also blocked IGF-1 induced IGF
      1R and Akt phosphorylation. Finally, it was demonstrated that pretreatment with
      CPT inhibited IGF-1 induced cell proliferation of A549 and H1299 cells. In
      conclusion, the results of the present study indicated that CPT inhibits the
      proliferation and migration of lung cancer cells via a mechanism that involves
      inhibiting the IGF-1R-mediated phosphoinositide 3-kinase/Akt signaling pathway.
      The data provides evidence that CPT could be developed as a potential therapeutic
      agent for the treatment of lung cancer.

PMID- 30106121
TI  - CIP2A depletion potentiates the chemosensitivity of cisplatin by inducing
      increased apoptosis in bladder cancer cells.
AB  - Poor response and chemotherapy resistance to cisplatin (DDP)-based therapy
      frequently lead to treatment failure in advanced bladder cancer; however the
      underlying mechanism is extremely complex and unclear. Furthermore, cancerous
      inhibitor of protein phosphatase 2A (CIP2A), a recently identified human
      oncoprotein, has been shown to play important regulatory roles in cancer cell
      survival. The present study aimed to investigate the correlation of CIP2A with
      sensitivity to DDP in bladder cancer cells. In the present study, knockdown of
      CIP2A was performed using short hairpin-RNA. IC50 determination was used to
      estimate the chemosensitivity of cells to DDP. Apoptosis and DNA damage
      indicators were tested in vitro and in vivo to clarify the role of CIP2A in
      enhancing DDP sensitivity. We observed that CIP2A knockdown enhanced DDP
      sensitivity. CIP2A depletion accelerated the process of DNA damage caused by DDP
      treatment. Furthermore, DDP triggered inhibition of CIP2A by preventing AKT
      Ser473 phosphorylation. In vivo, CIP2A suppression increased the cytotoxicity of
      DDP, which resulted in a decrease in the subcutaneous tumor growth in a xenograft
      mouse model. Our findings revealed that the mechanism underlying the involvement
      of CIP2A in DDP sensitivity enhancement is that CIP2A mediates DDP-induced cell
      apoptosis and DNA damage. CIP2A is a potential target to improve the response to
      DDP-based therapy in bladder cancer patients.

PMID- 30106124
TI  - Cold exposure promotes obesity and impairs glucose homeostasis in mice subjected
      to a high-fat diet.
AB  - Cold exposure is considered to be a form of stress and has various adverse
      effects on the body. The present study aimed to investigate the effects of
      chronic daily cold exposure on food intake, body weight, serum glucose levels and
      the central energy balance regulatory pathway in mice fed with a high-fat diet
      (HFD). C57BL/6 mice were divided into two groups, which were fed with a standard
      chow or with a HFD. Half of the mice in each group were exposed to ice-cold water
      for 1 h/day for 7 weeks, while the controls were exposed to room temperature.
      Chronic daily cold exposure significantly increased energy intake, body weight
      and serum glucose levels in HFD-fed mice compared with the control group. In
      addition, 1 h after the final cold exposure, c-fos immunoreactivity was
      significantly increased in the central amygdala of HFD-fed mice compared with HFD
      fed mice without cold exposure, indicating neuronal activation in this brain
      region. Notably, 61% of these c-fos neurons co-expressed the neuropeptide Y
      (NPY), and the orexigenic peptide levels were significantly increased in the
      central amygdala of cold-exposed mice compared with control mice. Notably, cold
      exposure significantly decreased the anorexigenic brain-derived neurotropic
      factor (BDNF) messenger RNA (mRNA) levels in the ventromedial hypothalamic
      nucleus and increased growth hormone releasing hormone (GHRH) mRNA in the
      paraventricular nucleus. NPY-ergic neurons in the central amygdala were activated
      by chronic cold exposure in mice on HFD via neuronal pathways to decrease BDNF
      and increase GHRH mRNA expression, possibly contributing to the development of
      obesity and impairment of glucose homeostasis.

PMID- 30106125
TI  - Metformin reverses stem cell-like HepG2 sphere formation and resistance to
      sorafenib by attenuating epithelial-mesenchymal transformation.
AB  - Cancer stem cells (CSCs) have been reported to be associated with the recurrence
      and drug resistance of liver cancer. In the present study, stem cell-like HepG2
      cell spheres were enriched using stem cell conditioned culture medium. As
      expected, stem-like HepG2 cell spheres exhibited increased resistance to
      sorafenib. Metformin, a common drug used to treat type 2 diabetes mellitus,
      reduced the diameters and numbers of stem-like HepG2 spheres, and increased their
      sensitivity to sorafenib. Western blotting confirmed that low doses of metformin
      reversed the epithelial-mesenchymal transformation (EMT) process of HepG2
      spheres. These results suggested that metformin enhanced sensitivity to
      sorafenib, which was probably through reversal of the EMT process of sphere
      forming cells and by reducing the formation of CSCs.

PMID- 30106123
TI  - Upregulated EFNB2 and EPHB4 promotes lung development in a nitrofen-induced
      congenital diaphragmatic hernia rat model.
AB  - Congenital diaphragmatic hernia (CDH) is a common congenital malformation
      associated with high mortality rates, mainly due to pulmonary hypoplasia and
      persistent pulmonary hypertension following birth. The present study aimed to
      investigate abnormal lung development in a rat CDH model, and examine temporal
      and spatial changes in the expression of ephrin type-B receptor 4 (EPHB4) and
      ephrin-B2 (EFNB2) during fetal lung development, to elucidate the role of these
      factors during lung morphogenesis. Pregnant rats received nitrofen on embryonic
      day (E) 8.5 to induce CDH, and fetal lungs were collected on E13.5, E15.5, E17.5,
      E19.5, and E21.5. The mean linear intercept (MLI) and mean alveolar number (MAN)
      were observed in fetal lung tissue at E21.5 following hematoxylin and eosin
      staining. E13.5 fetal lungs were cultured for 96 h in serum-free medium and
      branch development was observed under a microscope. The gene and protein
      expression levels of EPHB4 and EFNB2 were assessed by reverse transcription
      quantitative polymerase chain reaction analysis, and immunoblotting and
      immunohistochemistry, respectively. The fetal rat lungs were treated with EFNB2
      and the activity of key signaling pathways was assessed. The lung index (lung
      weight/body weight) at E21.5 was significantly lower in the CDH rats, compared
      with that in the control fetal rats. The MLI and MAN were also lower in the CDH
      group. The number of lung terminal buds at E13.5 (embryonic stage), and the lung
      explant perimeter and surface were all smaller in the CDH group rats than in the
      control group at the same age. Pulmonary hypoplasia was observed following 96 h
      of in vitro culture. No significant differences were found in the expression
      levels of EFNB2 and EPHB4 between the CDH and control groups at E13.5 (embryonic
      stage) or E15.5 (pseudoglandular stage), however, EFNB2 and EPHB4 were
      significantly upregulated at E17.5 (canalicular stage), and at E19.5 and E21.5
      (saccular/alveolar stages). EFNB2 stimulated pulmonary branching and EFNB2
      supplementation decreased the activity of p38, c-Jun NH2-terminal kinase,
      extracellular signal-regulated kinase, and signal transducer and activator of
      transcription. The CDH fetal rats developed pulmonary dysplasia at an early stage
      of fetal pulmonary development. Upregulated expression of EFNB2 and EPHB4 was
      observed in the rat lung of nitrofen-induced CDH, and the increased expression of
      EFNB2 promoted rat lung development in the nitrofen-induced CDH model.

PMID- 30106128
TI  - Stra8 may inhibit apoptosis during mouse spermatogenesis via the AKT signaling
      pathway.
AB  - Stimulated by retinoic acid 8 (Stra8), one of genes induced by retinoic acid
      (RA), is required for the meiotic initiation of male spermatogenesis. The present
      study found that Stra8 inhibited apoptosis in male Stra8-knockout mice, and in
      mice with vitamin A deficiency and vitamin A recovery in vivo. This phenotype was
      also verified in GC1 spermatogonia (spg) cells overexpressing Stra8. In addition,
      microarray analysis identified that there were nine differentially expressed
      genes (DEGs) in the Stra8-overexpressed GC1 spg cells compared with the control
      groups; the expression of these nine genes was verified via mRNA expression
      levels. The DEGs were as follows: Phosphatidylinositol-dependent kinase 1 (PDK1),
      a key gene upstream of protein kinase B (AKT); angiopoietin 2, a B-cell lymphoma
      2 (Bcl-2)-inhibited gene; transcription factor 4, glutathione S-transferase P91
      and ubiquitin-specific protease 33, mitogen-activated protein kinase (MAPK)
      related genes; oxidative stress induced growth inhibitor 1, related to the P53
      pathway; Bcl-2, P53, ERK (MAPK1/3), c-Jun N-terminal kinase (MAPK8/9), and P38
      (MAPK14), all of which are key genes involved in the AKT signaling pathway.
      Therefore, the present study further verified these genes and found that the mRNA
      and protein expression levels of PDK1, AKT, Bcl-2 and ERK were increased.
      Although the mRNA expression level of P53 was decreased, there was no significant
      difference in the protein expression level in Stra8-overexpressing GC1 spg cells
      compared with controls. In addition, Caspase 3, one of the executioner caspases,
      was decreased in Stra8-overexpressing GC1 spg cells compared with the control
      groups. Therefore, it was suggested that Stra8 may directly or indirectly inhibit
      caspases through the AKT signaling pathway and ultimately exert an anti-apoptotic
      effect in the male reproductive system.

PMID- 30106127
TI  - The PDK1/c-Jun pathway activated by TGF-beta induces EMT and promotes
      proliferation and invasion in human glioblastoma.
AB  - Glioblastoma multiforme (GBM) is the most common primary malignant tumor
      affecting the human brain. Despite improvements in therapeutic technologies,
      patients with GBM have a poor clinical result and the molecular mechanisms
      responsible for the development of GBM have not yet been fully elucidated. 3
      phosphoinositide dependent protein kinase 1 (PDK1) is upregulated in various
      tumors and promotes tumor invasion. In glioma, transforming growth factor-beta
      (TGF-beta) promotes cell invasion; however, whether TGF-beta directly regulates
      PDK1 protein and promotes proliferation and invasion is not yet clear. In this
      study, PDK1 levels were measured in glioma tissues using tissue microarray (TMA)
      by immunohistochemistry (IHC) and RT-qPCR. Kaplan-Meier analyses were used to
      calculate the survival rate of patients with glioma. In vitro, U251 and U87
      glioma cell lines were used for functional analyses. Cell proliferation and
      invasion were analyzed using siRNA transfection, MTT assay, RT-qPCR, western blot
      analysis, flow cytometry and invasion assay. In vivo, U251 glioma cell xenografts
      were established. The results revealed that PDK1 protein was significantly
      upregulated in glioma tissues compared with non-tumorous tissues. Furthermore,
      the higher PDK1 levels were associated with a large tumor size (>5.0 cm), a
      higher WHO grade and a shorter survival of patients with GBM. Univariate and
      multivariate analyses indicated that PDK1 was an independent prognostic factor.
      In vivo, PDK1 promoted glioma tumor xenograft growth. In vitro, functional
      analyses confirmed that TGF-beta upregulated PDK1 protein expression and PDK1
      promoted cell migration and invasion, and functioned as an oncogene in GBM, by
      upregulating c-Jun protein and inducing epithelial-mesenchymal transition (EMT).
      c-Jun protein were overexpressed in glioma tissues and positively correlated with
      PDK1 levels. Moreover, our findings were further validated by the online Oncomine
      database. On the whole, the findings of this study indicate that in GBM, PDK1
      functions as an oncogene, promoting proliferation and invasion.

PMID- 30106126
TI  - miR-291b-3p mediated ROS-induced endothelial cell dysfunction by targeting HUR.
AB  - Endothelial dysfunction is an early marker of atherosclerosis. Previous studies
      have indicated that microRNA (miR)-291b-3p regulates the metabolism of lipids and
      glucose in the liver via targeting adenosine monophosphate-activated kinase
      alpha1 and transcription factor p65. The present study investigated whether miR
      291b-3p mediated H2O2-mediated endothelial dysfunction. The level of apoptosis of
      EOMA mouse endothelial cells was analyzed by terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labelling staining. The mRNA levels of miR
      291b-3p, intercellular adhesion molecule-1 (ICAM-1) and vascular adhesion
      molecule-1 (VCAM-1) were determined by quantitative polymerase chain reaction.
      The level of phosphorylated extracellular signal-regulated kinase, and levels of
      B-cell lymphoma 2 (Bcl-2)-associated X protein and Bcl-2 protein were detected by
      western blot analysis. The treatment of H2O2 induced the apoptosis and increased
      the mRNA levels of miR-291b-3p, ICAM-1 and VCAM-1 in EOMA cells. It was also
      demonstrated that the overexpression of miR-291b-3p promoted EOMA cell apoptosis
      and dysfunction. In contrast, the downregulation of miR-291b-3p rescued the
      effect of H2O2 on EOMA cell dysfunction. In addition, Hu antigen R (HuR) was
      identified as a target gene of miR-291b-3p in EOMA cells. The overexpression of
      HuR reversed the endothelial dysfunction induced by miR-291b-3p mimics. The
      present study provides novel insight into the critical role of miR-291b-3p on the
      endothelial dysfunction induced by H2O2. miR-291b-3p may mediate H2O2-induced
      endothelial dysfunction via targeting HuR.

PMID- 30106129
TI  - Nkd2 promotes the differentiation of dental follicle stem/progenitor cells into
      osteoblasts.
AB  - Dental follicle stem/progenitor cells have the potential to undergo osteogenesis.
      naked cuticle homolog 2 (Nkd2) is a signal-inducible feedback antagonist of the
      canonical Wnt signaling pathway. The purpose of the present study was to
      investigate the function of Nkd2 in the differentiation of dental follicle
      stem/progenitor cells (DFSCs) into osteoblasts. Immunohistochemistry, reverse
      transcription-quantitative polymerase chain reaction and western blotting were
      employed to detect Nkd2 expression in rat DFSCs. In addition, rat DFSCs (rDFSCs)
      were transfected with small interfering RNAs to examine the effect of Nkd2 on the
      differentiation of these cells into osteoblasts. Furthermore, the function of
      Nkd2 in the Wnt/beta-catenin pathway in rDFSCs was investigated using beta
      catenin/T-cell factor luciferase activity assays and western blotting. It was
      revealed that the expression of Nkd2 was upregulated during the differentiation
      of rDFSCs into osteoblasts. Furthermore, osteoblast differentiation ability and
      Wnt/beta-catenin pathway activity were significantly decreased in Nkd2-silenced
      rDFSCs compared with the si-NC group (P<0.05 and P<0.001, respectively). The
      results suggest that Nkd2 promotes the differentiation of rDFSCs into osteoblasts
      through Wnt/beta-catenin signaling.

PMID- 30106132
TI  - hnRNPK modulates selective quality-control autophagy by downregulating the
      expression of HDAC6 in 293 cells.
AB  - hnRNPK modulates selective quality-control autophagy bAbstract. A recent study
      has reported that heterogeneous nuclear ribonucleoprotein K (hnRNPK) regulated
      autophagy in leukemia cells. However, the underlying mechanism of this remains
      elusive. The present study assessed the role of hnRNPK in the autophagy of the
      293 cell line and investigated the associated molecular mechanisms of this. It
      was revealed that hnRNPK-knockdown with siRNA or the CRISPR-Cas9 system could
      increase the level of autophagy, while hnRNPK-overexpression exerted the opposite
      effect in 293 cells under normal nutrient conditions. By contrast, hnRNPK
      knockdown or -overexpression had no effect on serum starvation- or rapamycin
      induced autophagy. Therefore, hnRNPK was likely involved in the late stage of
      autophagy rather than the early stage. Furthermore, it was observed that hnRNPK
      deficiency led to the decrease in alpha-tubulin K40 acetylation in hnRNPK single
      allele knockout (hnRNPK+/-) cells. In accordance with this result, it was
      revealed that the mRNA and protein levels of histone deacetylas 6 (HDAC6) were
      upregulated in hnRNPK+/- cells compared with the wild-type cells. As a
      consequence, autophagosome-lysosome fusion in hnRNPK+/- cells was significantly
      enhanced and could be effectively suppressed by treatment with the selective
      inhibitor of HDAC6, tubastatin A (Tub A). Furthermore, prominent co-localization
      of ubiquitin-positive aggregates with LC3-positive autophagosomes was observed in
      hnRNPK+/- cells, but not in the wild-type or hnRNPK+/- cells treated with Tub A.
      Taken together, these results suggested that hnRNPK may regulate basal autophagy
      through modulating the expression level of HDAC6 to influence the autophagosome
      lysosome fusion.

PMID- 30106131
TI  - Upregulation of HOXA11 during the progression of lung adenocarcinoma detected via
      multiple approaches.
AB  - The altered expression of homeobox (HOX)A11 has been observed in various
      malignant tumor types, but it has remained to be determined in human lung
      adenocarcinoma (LUAD). In the present study, the expression of HOXA11 in LUAD and
      the potential associated mechanisms were assessed. Data from The Cancer Genome
      Atlas and Oncomine microarrays were gathered and in-house polymerase chain
      reaction data were produced to investigate the altered expression of HOXA11 in
      LUAD and its association with various clinicopathological characteristics. Genes
      co-expressed with HOXA11 were also identified by searching the cBioPortal and
      Multi Experiment Matrix databases, and performing a bioinformatics analysis,
      through which the potential molecular mechanisms of HOXA11 in LUAD were explored.
      The data analyses indicated that HOXA11 was overexpressed in the LUAD samples,
      and together with its co-expressed genes, it was indicated to participate in
      various key signaling pathways, including the focal adhesion, extracellular
      matrix-receptor interaction, axon guidance and small cell lung cancer signaling
      pathways. Furthermore, collagen type III alpha 1 chain (COL3A1), ephrin B2
      (EFNB2), integrin subunit alpha 8 (ITGA8) and syndecan 2 (SDC2) were confirmed to
      be differentially expressed in LUAD vs. normal controls at the mRNA and protein
      level. Of note, LUAD patients with low expression of HOXA11 and ITGB1 had better
      overall survival rates. The present study indicated that HOXA11 may function as
      an oncogene in LUAD, and HOXA11 protein probably combines with ITGB1, COL3A1,
      EFNB2, ITGA8 and SDC2 to have a role in the focal adhesion pathway.

PMID- 30106130
TI  - Human non-small cell lung cancer cells can be sensitized to camptothecin by
      modulating autophagy.
AB  - Lung cancer is a prevalent disease and is one of the leading causes of mortality
      worldwide. Despite the development of various anticancer drugs, the prognosis of
      lung cancer is relatively poor. Metastasis of lung cancer, as well as
      chemoresistance, is associated with a high mortality rate for patients with lung
      cancer. Camptothecin (CPT) is a well-known anticancer drug, which causes cancer
      cell apoptosis via the induction of DNA damage; however, the cytotoxicity of CPT
      easily reaches a plateau at a relatively high dose in lung cancer cells, thus
      limiting its efficacy. The present study demonstrated that CPT may induce
      autophagy in two human non-small cell lung cancer cell lines, H1299 and H460. In
      addition, the results of a viability assay and Annexin V staining revealed that
      CPT-induced autophagy could protect lung cancer cells from programmed cell death.
      Conversely, the cytotoxicity of CPT was increased when autophagy was blocked by 3
      methyladenine treatment. Furthermore, inhibition of autophagy enhanced the levels
      of CPT-induced DNA damage in the lung cancer cell lines. Accordingly, these
      findings suggested that autophagy exerts a protective role in CPT-treated lung
      cancer cells, and the combination of CPT with a specific inhibitor of autophagy
      may be considered a promising strategy for the future treatment of lung cancer.

PMID- 30106133
TI  - Shikonin sensitizes wild-type EGFR NSCLC cells to erlotinib and gefitinib
      therapy.
AB  - As patients with non-small cell lung cancer (NSCLC) and wild-type epidermal
      growth factor receptor (EGFR) are resistant to treatment with erlotinib or
      gefitinib, potential chemosensitizers are required to potentiate wild-type EGFR
      NSCLC cells to erlotinib/gefitinib treatment. The present study reported that
      shikonin could sensitize the anticancer activity of erlotinib/gefitinib in wild
      type EGFR NSCLC cells. Furthermore, shikonin could potentiate mitochondrial
      mediated apoptosis induced by erlotinib/gefitinib in wild-type EGFR NSCLC cells.
      In addition, the present study demonstrated that shikonin could induce apoptosis
      by activating reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER)
      stress, and that erlotinib/gefitinib may also induce ER stress in wild-type EGFR
      NSCLC cells; however, shikonin plus erlotinib/gefitinib was more effective in
      activating ER stress than either agent alone. This indicated that ROS-mediated ER
      stress may be associated with enhanced mitochondrial apoptosis induced by
      shikonin plus erlotinib/gefitinib. In addition, shikonin may promote the
      transition of cytoprotective ER stress-inducing EGFR-tyrosine kinase inhibitor
      tolerance to apoptosis-promoting ER stress. Furthermore, shikonin may enhance the
      anti-NSCLC activity of erlotinib/gefitinib in vivo. The data of the present study
      indicated that shikonin may be a potential sensitizer to enhance the anti-cancer
      efficacy of erlotinib/gefitinib in wild-type EGFR NSCLC cells resistant to
      erlotinib/gefitinib treatment.

PMID- 30106134
TI  - Effects of Toll-like receptor 9 and CpG oligodeoxynucleotides 1826 on sodium
      taurocholate-induced acute pancreatitis rats.
AB  - The aim of the present study was to investigate the effects of Toll-like receptor
      (TLR) 9 and CpG oligodeoxynucleotide (CpG-ODN)1826 on sodium taurocholate-induced
      acute pancreatitis (AP) rats at different time points. Pathological examination
      indicated that the severity of pancreatic tissue damage following AP increased
      with time. Additionally, TLR9 protein levels were upregulated after AP, and were
      higher at 6 h compared with at 3 h. Subsequently, the TLR9 protein levels were
      downregulated at 12 h, but remained higher than the control group. In rats
      subjected to AP, tumor necrosis factor (TNF-alpha protein expression levels and
      serum amylase (AMS) in the serum were increased until 12 h. The expression level
      of TNF-alpha protein in the AP 12 h group was higher than that in the AP 3 and 6
      h groups. In addition, following CpG-ODN1826 administration, the morphology of
      pancreatic tissue appeared worse compared with that in the AP only groups.
      Furthermore, CpG-ODN1826 administration induced an increase in TLR9 expression
      levels compared with the AP alone group at 0, 3, 6 and 12 h. TNF-alpha in the CpG
      + AP 12 h group was upregulated compared with that in the CpG + AP 3 and 6 h
      groups; however, no change was observed between 3 and 6 h. Thus, these data
      indicate that CpG-ODN1826 aggravates sodium taurocholate-induced pancreas damage
      in rats.

PMID- 30106135
TI  - Membrane proteomics of cervical cancer cell lines reveal insights on the process
      of cervical carcinogenesis.
AB  - The available therapeutic approaches for cervical cancer can seriously affect the
      fertility potential of patient; thus, there is a pressing requirement for less
      toxic and targeted therapies. The membrane proteome is a potential source of
      therapeutic targets; however, despite the significance of membrane proteins in
      cancer, proteomic analysis has been a challenging task due to their unique
      biochemical properties. The aim of the present study was to develop an efficient
      membrane protein enrichment protocol, and to the best of our knowledge, to
      compare for the first time the expression pattern of membrane proteins of one
      normal cell line, HCK1T, and three cervical cancer cell lines, C33A, a human
      papilloma virus (HPV)-negative cell line, and two HPV-positive cell lines, SiHa
      (HPV16+) and HeLa (HPV18+). The study aimed to identify the proteins that are
      involved in cervical carcinogenesis and may constitute novel drug targets.
      Membrane protein isolation, liquid chromatography coupled with tandem mass
      spectrometry proteomics and bioinformatics analysis were performed in the
      membrane fraction of the informative cervical cell lines following a novel
      enrichment protocol. The percentages of membrane and transmembrane proteins in
      the enrichment protocol were higher compared with those of the corresponding data
      derived from total cell extract analysis. Differentially expressed proteins were
      detected by the comparison of the cervical cancer cell lines with the normal cell
      line. These proteins constitute molecular features of cancer pathology and
      participate in biological pathways relevant to malignancy, including 'HIPPO
      signaling', 'PI3K/Akt signaling', 'cell cycle: G2/M DNA damage checkpoint
      regulation' and 'EIF2 signaling'. These unique membrane protein identifications
      offer insights on a previously inaccessible region of the cervical cancer
      proteome, and may represent putative diagnostic and prognostic markers, and
      eventually therapeutic targets.

PMID- 30106136
TI  - ZBTB7 evokes 5-fluorouracil resistance in colorectal cancer through the NF-kappaB
      signaling pathway.
AB  - Zinc finger and BTB domain containing 7A (ZBTB7), a POZ/BTB and Kruppel erythroid
      myeloid oncogenic factor, is critical for the tumorigenicity and progression of
      various cancer types. ZBTB7 has been reported to promote the cell proliferation
      of colorectal cancers (CRC). However, the function of ZBTB7 to 5-fluorouracil (5
      FU) resistance has not yet been studied. In the current study, ZBTB7 expression
      and function in 5-FU resistance in CRC were investigated using with
      multidisciplinary approaches, including western blot analysis, Transwell assay,
      CCK8 and a tumor xenograft model. Overexpression of ZBTB7 was increased the level
      of proteins associated with cell invasion and epithelial-mesenchymal transition.
      ZBTB7 inhibition attenuated the invasion and enhanced the apoptosis of CRC cells.
      IC50 values and cell viability were significantly reduced in cells with short
      hairpin RNA (shRNA)-mediated ZBTB7 depletion compared with the control group. 5
      FU administration decreased viability to a greater extent in the ZBTB7-shRNA
      group compared with the control, which was dose- and time-dependent. Analysis of
      gene expression omnibus data demonstrated that ZBTB7 mediated 5-FU resistance,
      potentially through nuclear factor (NF)-kappaB signaling. NF-kappaB inhibitor
      SN50 reversed ZBTB7-induced resistance in CRC. Collectively, the findings
      demonstrated that ZBTB7 mediated 5-FU resistance in CRC cells through NF-kappaB
      signaling. Thus, targeting ZBTB7 and NF-kappaB signaling may be an effective
      strategy to reverse 5-FU resistance in CRC.

PMID- 30106137
TI  - Gene regulatory network construction identified NFYA as a diffuse subtype
      specific prognostic factor in gastric cancer.
AB  - Lauren classification is a pathology-based gastric cancer (GC) subtyping system,
      which is widely used in the clinical treatment of patients with GC. However,
      genome-scale molecular characteristics to distinguish between diffuse (DF) and
      intestinal (IT) GC remain incompletely characterized, particularly at the
      transcriptional regulatory level. In the present study, gene regulatory networks
      were constructed using the Passing Attributes between Networks for Data
      Assimilation (PANDA) algorithm for DF, IT and mixed GC. The results indicated
      that >85% of transcription factor (TF)-target edges were shared among all three
      GC subtypes. In TF enrichment analysis, 13 TFs, including nuclear transcription
      factor Y subunit alpha (NFYA) and forkhead box L1, were activated in DF GC,
      whereas 8 TFs, including RELA proto-oncogene and T-cell leukemia homeobox 1
      (TLX1), were activated in IT GC. Out of these identified TFs, NFYA [Hazard ratio
      (HR) (95% confidence interval, CI)=0.560 (0.349, 0.900), P=0.017] and sex
      determining region Y [HR (95% CI)=0.603 (0.375, 0.969), P=0.037] were identified
      as independent prognostic factors in DF GC, but not in IT GC, whereas TLX1 [HR
      (95% CI)=0.547 (0.321, 0.9325), P=0.027] was identified as an independent
      prognostic factor in IT GC, but not in DF GC. Verification at the cellular level
      was also performed; interference of NFYA expression using small interfering RNA
      in MGC803 cells (DF GC-derived cells) markedly inhibited cell growth and colony
      formation. Similar effects were also detected in SGC-7901 cells (IT GC-derived
      cells), but to a lesser extent. In conclusion, identified gene regulatory
      networks differed between distinct GC subtypes, in which the same TFs had
      different biological effects. Specifically, NFYA was identified as a DF subtype
      specific independent prognostic factor in GC.

PMID- 30106139
TI  - Long non-coding RNA CASC2 inhibits breast cancer cell growth and metastasis
      through the regulation of the miR-96-5p/SYVN1 pathway.
AB  - Cancer susceptibility candidate 2 (CASC2), a long non-coding RNA (lncRNA), has
      been demonstrated to be a tumor suppressor in several types of cancer. However,
      the role and mechanism of CASC2 in breast cancer (BC) have not been investigated.
      In the present study, the expression and functions of CASC2 in BC were
      investigated. The expression of CASC2 was significantly decreased in BC tissues
      and cells compared with adjacent normal tissues and mammary epithelial cells,
      respectively. CASC2 overexpression inhibited the viability, migration and
      invasion, and elevated apoptosis of BC cells. In addition, CASC2 acted as a
      competing endogenous RNA for hsa-microRNA (miR)-96-5p and regulated the
      expression of its target gene, synoviolin (SYVN1). In miR-96-5p-overexpressed MDA
      MB-231 cells, cell viability, migration and invasion was increased, and cell
      apoptosis was decreased, which was reversed by the upregulation of SYVN1. Taken
      together, the present study data indicated that decreased SYVN1 expression was a
      tumor suppressor, which inhibited the growth and metastasis of BC through the miR
      96-5p/SYVN1 axis.

PMID- 30106138
TI  - Risk assessment model constructed by differentially expressed lncRNAs for the
      prognosis of glioma.
AB  - A risk assessment model was constructed using differentially expressed long non
      coding (lnc)RNAs for the prognosis of glioma. Transcriptome sequencing of the
      lncRNAs and mRNAs from glioma samples were obtained from the TCGA database. The
      samples were divided into bad and good prognosis groups based on survival time,
      then differently expressed lncRNAs between these two groups were screened using
      DEseq and edgeR packages. Multivariate Cox regression analysis was performed to
      establish a risk assessment system according to the weighted regression
      coefficient of lncRNA expression. Survival analysis and receiver operating
      characteristic curve were conducted for the risk assessment model. Furthermore,
      the co-expression network of the screened lncRNAs was constructed, followed by
      the functional enrichment analysis for associated genes. A total of 117 lncRNAs
      were screened using edgeR and DEseq packages. Among all differently expressed
      lncRNAs, five lncRNAs (RP3-503A6, LINC00940, RP11-453M23, AC009411 and CDRT7)
      were identified to establish the risk assessment model. The risk assessment model
      demonstrated a good prognostic function with high area under the curve values in
      the training, validation and entire sets. The risk score was certified as an
      independent prognostic factor for gliomas. Multiple genes were screened to be co
      expressed with these five lncRNAs. Functional enrichment analysis demonstrated
      that they were involved in cytoskeleton, adhesion and Janus kinase/signal
      transducer and activator of transcription signaling pathway-associated processes.
      The present study established a risk assessment model integrating five
      significantly different expressed lncRNAs, which may help to assess the prognosis
      of patients with glioma with increased accuracy.

PMID- 30106141
TI  - Nogo-B receptor in relevant carcinoma: Current achievements, challenges and aims
      (Review).
AB  - The novel neurite outgrowth inhibitor B (Nogo-B) receptor (NgBR) is specific for
      Nogo-B, which is highly expressed in various human organs and cells, including
      the lung, liver, kidney, smooth muscle cells, blood vessel endothelial cells and
      inflammatory cells. Previous studies have indicated that NgBR directly interacts
      with Nogo-B and is able to independently influence lipid and cholesterol
      homeostasis, angiogenesis, N-glycosylation, the epithelial-mesenchymal
      transition, the chemotaxis of endothelial cells and cellular proliferation and
      apoptosis. These multiple functions and actions of this receptor provide an
      understanding of the important roles of NgBR in various conditions, including
      fatty liver, atherosclerosis, intracranial microaneurysms, retinitis pigmentosa
      and severe neurological impairment. Furthermore, NgBR has been demonstrated to
      exert protean, multifunctional and enigmatic effects in cancer. The present
      review summarizes the latest knowledge on the suppressing and activating effects
      of NgBR, emphasizing its function in cancer. Further basic and medical research
      on this receptor may provide novel insight into its clinical implications on the
      prognosis of relevant human cancer types.

PMID- 30106140
TI  - lncRNA LINC00673 induces proliferation, metastasis and epithelial-mesenchymal
      transition in thyroid carcinoma via Kruppel-like factor 2.
AB  - The incidence of thyroid cancer has increased in the past decades; however, the
      underlying molecular mechanisms of thyroid cancer tumorigenesis remain unknown.
      Using sequencing technology, long intergenic non-protein coding RNA 673
      (LINC00673) was identified to be upregulated in several tumor tissues. However,
      the biological role of LINC00673 in thyroid carcinoma has yet to be determined.
      In this study, 60 matched pairs of thyroid tumor tissue and normal tissue were
      selected for study using reverse transcription-quantitative polymerase chain
      reaction (RT-qPCR) to validate previous findings; then, clinicopathologic
      features of the tissues were analyzed. Proliferation, colony formation, migration
      and invasion assays were performed, and epithelial-mesenchymal transition (EMT)
      associated phenotypes were investigated following transfection with small
      interfering RNA to determine the specific role of LINC00673 in thyroid carcinoma
      cell lines (TPC1, KTC-1 and BCPAP). The study revealed that long non-coding RNA
      LINC00673 was significantly upregulated in thyroid cancer tissues compared with
      paired adjacent non-tumor tissues using RT-qPCR and that high expression of
      LINC00673 is was associated with larger tumor size and lymph node metastasis in
      the validated cohort. Knockdown of LINC00673 inhibited cell proliferation and
      metastasis, whereas, LINC00673 overexpression had the opposite effect. The
      results showed that LINC00673 may influence EMT and the expression of Kruppel
      like factor 2 (KLF2). Notably, KLF2 is considered a tumor suppressor gene in a
      variety of tumors. Finally, knock down of KLF2 enhanced thyroid carcinoma cell
      proliferation, and invasion and migration. In this study, the function of
      LINC00673 in promoting the proliferation and metastasis of thyroid carcinoma cell
      lines was identified, and LINC00673 may act as a novel therapeutic target for
      treating thyroid carcinoma.

PMID- 30106142
TI  - Overexpression of KLF5 inhibits puromycin-induced apoptosis of podocytes.
AB  - Diabetic nephropathy (DN) is one of the most common microvascular complications
      associated with diabetes mellitus (DM); the incidence has been predicted to reach
      7.7% by 2030 on a global scale. Kruppel-like factor 5 (KLF5) is involved in
      numerous important biological processes; however, the potential effects of KLF5
      on podocytes in patients with diabetic nephrotic (DN) have not yet been
      investigated. In the present study, synaptopodin expression in podocytes was
      investigated using an immunofluorescence assay. Following this, the proliferation
      of podocytes was investigated using an MTT assay. In addition, KLF5 was
      overexpressed in podocytes, and cell cycle arrest and apoptosis was subsequently
      investigated using flow cytometry. Western blotting and reverse transcription
      quantitative polymerase chain reaction assays were performed to detect the
      expression levels of genes involved in the cell cycle and apoptosis, and the
      extracellular signal-regulated protein kinase (ERK)/p38 mitogen-activated protein
      (MAP) kinase pathway. The results demonstrated that treatment with puromycin
      aminonucleoside (PAN) suppressed the proliferation of podocytes in a dose- and
      time-dependent manner, and overexpression of KLF5 induced cell cycle arrest of
      podocytes regulated by PAN. Furthermore, overexpression of KLF5 was revealed to
      have inhibited PAN-induced apoptosis of podocytes, and that overexpression of
      KLF5 suppressed the ERK/p38 MAP kinase pathway in podocytes induced by PAN.
      Therefore, the results of the present study suggested that KLF5 may represent a
      potential therapeutic target for treatment of patients with DN.

PMID- 30106143
TI  - Transcriptome sequencing identifies key pathways and genes involved in gastric
      adenocarcinoma.
AB  - The present study aimed to investigate the key pathways and genes associated with
      gastric adenocarcinoma via transcriptome sequencing. Five pairs of gastric
      adenocarcinoma tissue and normal tumor-adjacent tissue were harvested. After
      sequencing, raw data were processed and differentially expressed genes (DEGs)
      between tumor and control groups were screened, followed by functional enrichment
      analysis and gene clustering analysis. The effect of DEGs on patient prognosis
      was analyzed on the basis of the survival data from gastric adenocarcinoma
      patients in The Cancer Genome Atlas database. Several genes were validated
      through reverse transcription-quantitative polymerase chain reaction. In total,
      1,477 upregulated and 282 downregulated DEGs were screened in tumor groups. These
      genes were segregated into four clusters. Genes in cluster 1 were significantly
      involved in metabolism of xenobiotics by cytochrome P450, genes in cluster 2 were
      majorly involved in apoptosis, tight junction formation, and platelet activation,
      genes in cluster 3 were primarily enriched in the p53 signaling pathway and genes
      in cluster 4 were significantly enriched in the insulin resistance pathway.
      Furthermore, 15 DEGs significantly influenced prognosis, including F2R, CTHRC1,
      and RASGRP3. The expression levels of CYP2B6, MAPK13, CTHRC, RASGRP3 and PYGM
      were consistent with our analysis results. In conclusion, pathways for metabolism
      of xenobiotics via cytochrome P450, apoptosis, tight junction formation, platelet
      activation, and insulin resistance may serve important roles in the progression
      of gastric adenocarcinoma. Notably, CTHRC1 and RASGRP3 may serve as key
      prognostic markers.

PMID- 30106144
TI  - A natural ent-kaurane diterpenoid induces antiproliferation in ovarian cancer
      cells via ERK1/2 regulation and inhibition of cellular migration and invasion.
AB  - Ovarian cancer is one of the most common causes of female mortalities from
      gynecological tumors. An ent-kaurane diterpenoid compound CRT1 (ent-18-acetoxy
      7beta-hydroxy kaur-15-oxo-16-ene), mainly isolated from the Vietnamese herb
      Croton tonkinesis has been used in folk medicine in Vietnam for cancer treatment.
      However, the effect of this compound on human ovarian cancer cells has not yet
      been reported. The objective of the present study was to determine the effect of
      CRT1 on the cell viability, apoptosis and metastasis of SKOV3 human ovarian
      cancer cells using a Cell Counting Kit-8 assay, flow cytometric analysis of
      Annexin V-fluorescein isothiocyanate/propidium iodide staining, western blot
      analysis, soft agar colony forming assay, wound healing assay and Matrigel
      invasion assay. The results revealed that CRT1 possessed significant anti
      proliferative effects on SKOV3 cells. CRT1 treatment at 25 and 50 uM induced
      apoptosis, enhanced the percentage of Annexin V-positive cells, increased the
      expression of pro-apoptotic protein B-cell lymphoma 2 (Bcl-2)-associated X
      protein, cytochrome c release from the mitochondria to the cytosol, cleaved
      caspase-3, caspase-7, caspase-9, and poly (adenosine diphosphate-ribose)
      polymerase. However, it decreased the expression of Bcl-2 in a dose-dependent
      manner. The percentage of necrotic cells increased following CRT1 treatment at
      <10 uM. CRT1 at 50 uM significantly induced the phosphorylation of extracellular
      signal-regulated kinase (ERK). Growth inhibition and the apoptotic effects of
      CRT1 could be reversed by PD98059, an ERK inhibitor. Additionally, CRT1 inhibited
      cell migration and invasion via ERK1/2 activation in SKOV3 cells. These results
      indicated that CRT1, an ent-kaurane diterpenoid, may be a potential inhibitor of
      ovarian cancer by the activating ERK1/2/p90 ribosomal S6 kinase signaling
      pathway.

PMID- 30106146
TI  - C-C chemokine receptor type 3 gene knockout alleviates inflammatory responses in
      allergic rhinitis model mice by regulating the expression of eosinophil granule
      proteins and immune factors.
AB  - The present study aimed to investigate the effects of C-C chemokine receptor type
      3 (CCR3) gene knockout on allergic rhinitis (AR) in mice, as well as the
      underlying molecular mechanisms. Ovalbumin was administrated to CCR3+/+ and CCR3
      /- BALB/c mice to establish an AR model. The mice were divided into four groups:
      i) Normal control (CG), ii) AR model (AR), iii) CCR3 knockout CG (CCR3-/-CG) and
      iv) AR model with CCR3 knockout (CCR3-/-AR). Histological sections of nasal
      mucosae were examined by hematoxylin and eosin staining, which revealed that CCR3
      knockout suppressed the invasion of inflammatory cells and relieved the damage of
      nasal mucosae. Peripheral blood smear and nasal-washing smears were evaluated by
      Wright's staining. Eosinophil (EOS) numbers in nasal mucosae, peripheral blood,
      and nasal washings of the various groups were ranked in the order: AR>CCR3-/
      AR>CG>CCR3-/-. mRNA expression levels of CCR3, EOS peroxidase (EPO), EOS cationic
      protein (ECP), and major basic protein (MBP) in the peripheral serum and nasal
      washings were detected by reverse transcription-polymerase chain reaction.
      Interferon-gamma (IFN-gamma), interleukin (IL)-4, IL-10, and immunoglobulin E
      (IgE) protein levels in the peripheral serum and nasal washings were investigated
      by ELISA. CCR3 mRNA expression was not detected in the CCR3-/- and CCR3-/-AR
      groups, whereas expression levels in the AR group were markedly higher compared
      with expression in the CG group. Compared with the CG-associated groups (i.e.,
      the CG and CCR3-/-CG groups), the levels of EPO, ECP, MBP, IL-4, and IgE were
      significantly increased in the AR-associated groups (that is, R and CCR3-/-AR).
      In addition, the CCR3-/-AR group mice produced significantly lower levels of EPO,
      ECP, MBP, IL-4 and IgE compared with the AR group, whereas the expression levels
      of IFN-gamma and IL-10 were increased. CCR3 gene knockout may alleviate EOS
      invasion and the inflammatory response in AR model mice by reducing the
      expression levels of EPO, ECP, MBP, IL-4, and IgE, and increasing the expression
      of IL-10 and IFN-gamma.

PMID- 30106147
TI  - ASCL2 expression contributes to gastric tumor migration and invasion by
      downregulating miR223 and inducing EMT.
AB  - Achaete-scute homolog 2 (ASCL2), a basic helix-loop-helix transcription factor,
      serves an essential role in the maintenance of adult intestinal stem cells and
      the growth of gastric cancer (GC). However, the function of ASCL2 in the
      metastasis of GC is poorly understood. The present study aimed to evaluate the
      effect of ASCL2 expression on gastric tumor metastasis. ASCL2 protein expression
      was detected in 32 cases of gastric metastasis and its relevant primary tumors
      using western blotting and immunohistochemistry. The data suggested that the
      expression of ASCL2 was highest in metastatic tumors, among adjacent normal
      tissues, primary gastric tumors and gastric metastatic tumors. Furthermore, ASCL2
      overexpressing GC cell lines MKN1-ASCL2 and SNU16-ASCL2 were established. An in
      vitro assay suggested that microRNA 223 (miR223) expression was downregulated
      following ASCL2 overexpression, and that the expression of the epithelium
      associated protein E-cadherin was significantly decreased, while a series of
      mesenchyme-associated proteins, including zinc finger E-box-binding homeobox 1
      (Zeb-1), twist-related protein 1, integrin, vimentin, 72 kDa type IV collagenase
      and matrix metalloproteinase-9 were upregulated in ASCL2-overexpressing cells.
      Overexpression of miR223 attenuated the epithelial-mesenchymal transition (EMT)
      promoting effect induced by ASCL2 expression. In addition, the results of the
      chromatin immunoprecipitation and luciferase reporter gene assays indicated that
      ASCL2 was able to interact with the promoter of pre-miR223, and to inhibit the
      maturation of miR223, which may interact with the 3' untranslated region of Zeb-1
      and inhibit EMT in tumor cells. The results of the present study demonstrated
      that ASCL2 was able to downregulate the expression level of miR223, contribute to
      EMT and promote gastric tumor metastasis, which indicated that ASCL2 may serve as
      a therapeutic target in the treatment of GC.

PMID- 30106148
TI  - Selective activation of inflammation factors by human parvovirus B19 and human
      bocavirus VP1 unique region on H9c2 cardiomyocyte.
AB  - Human parvovirus B19 (B19) and human bocavirus 1 (HBoV) are the only known
      pathogenic parvoviruses, and are responsible for a variety of diseases in human
      beings. Mounting evidence indicates a strong association between B19 infection
      and cardiac disorders including myocarditis, dilated cardiomyopathy and heart
      failure. However, very limited information about the role of HBoV in cardiac
      disorders is known. To elucidate the effects of B19 and HBoV on cardiac
      disorders, we expressed EGFP-conjugate constructs of B19-VP1 unique region (VP1u)
      and HBoV-VP1u, along with the mutants EGFP-B19-VP1uD175A and EGFP-HBoV-VP1uV12A,
      in H9c2 cells by stable transfection. The protein expression levels of EGFP, EGFP
      B19-VP1u, EGFP-B19-VP1uD175A, EGFP-HBoV-VP1u and EGFP-HBoV-VP1uV12A in H9c2 cells
      were observed under a fluorescence microscope and confirmed by western blotting.
      Secreted phospholipase A2 (sPLA2) activity was detected in B19-VP1u and HBoV-VP1u
      but not B19-VP1uD175A and HBoV-VP1uV12A recombinant proteins. Significantly
      higher expression levels of MCP2 and IP-10 mRNA were detected in H9c2 cells that
      were transfected with pEGFP-B19-VP1u, compared with in those cells transfected
      with pEGFP-HBoV-VP1u, pEGFP-B19-VP1uD175A or pEGFP-HBoV-VP1uV12A. Significantly
      higher protein levels of IL-1beta and IL-6 were detected in H9c2 cells
      transfected with pEGFP-B19-VP1u or pEGFP-HBoV-VP1u, compared with in those cells
      transfected with pEGFP-B19-VP1uD175A or pEGFP-HBoV-VP1uV12A. Notably,
      significantly higher expression of both TNF-alpha and NF-kappaB was observed only
      in H9c2 cells transfected with pEGFP-B19-VP1u, but not in those cells transfected
      with pEGFP-HBoV-VP1u, pEGFP-B19-VP1uD175A or pEGFP-HBoV-VP1uV12A. These findings,
      to our knowledge for the first time, reveal the difference between B19-VP1u and
      HBoV-VP1u in H9c2 cells and provide insight into the roles of B19-VP1u and HBoV
      VP1u in the pathogenesis of cardiac inflammation.

PMID- 30106145
TI  - PI3K/Akt and HIF-1 signaling pathway in hypoxia-ischemia (Review).
AB  - Hypoxia-ischemia (H-I) is frequently observed in perinatal asphyxia and other
      diseases. It can lead to serious cardiac injury, cerebral damage, neurological
      disability and mortality. Previous studies have demonstrated that the
      phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway,
      which regulates a wide range of cellular functions, is involved in the resistance
      response to H-I through the activation of proteins associated with survival and
      inactivation of apoptosis-associated proteins. It can also regulate the
      expression of hypoxia-induced factor-1alpha (HIF-1alpha). HIF-1alpha can further
      regulate the expression of downstream proteins involved in glucose metabolism and
      angiogenesis, such as vascular endothelial growth factor and erythropoietin, to
      facilitate ischemic adaptation. Notably, HIF-1alpha may also induce detrimental
      effects. The effects of HIF-1 on ischemic outcomes may be dependent on the H-I
      duration, animal age and species. Thus, further investigation of the PI3K/Akt
      signaling pathway may provide further insights of the potential targets for
      treating diseases accompanied by H-I.

PMID- 30106149
TI  - Geranylgeranyl transferase 1 inhibitor GGTI-298 enhances the anticancer effect of
      gefitinib.
AB  - Dysregulation of epidermal growth factor receptor (EGFR) signaling is responsible
      for the resistance to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib
      and erlotinib, and is thereby associated with the progression of tumors in non
      small cell lung cancers (NSCLCs). Immunoblotting results revealed that
      geranylgeranyl transferase 1 inhibitor (GGTI)-298, a geranylgeranyl transferase 1
      inhibitor with potential antitumor effects, effectively inhibited the
      phosphorylation of EGFR and its downstream target protein kinase B (AKT). A
      combination of gefitinib and GGTI-298 amplified the inhibition of the EGFR-AKT
      signaling pathway. In addition, GGTI-298 treatment produced a synergistic effect
      on the inhibition of proliferation as indicated by the combination index values
      of <1 when combined with gefitinib in the NSCLC cell lines HCC827 and A549. These
      synergistic effects were also observed to induce apoptosis and migration
      inhibition. Further mechanistic studies demonstrated that GGTI-298 inhibited the
      activity of Ras homolog family member A (RhoA), and downregulation of RhoA with
      small interfering RNA impaired the phosphorylation of EGFR, which suggested that
      EGFR inhibition by GGTI-298 may be exerted mainly through RhoA mediation. These
      results presented a novel, promising therapeutic strategy involving a combination
      of two drugs for targeting EGFR signaling in lung cancer.

PMID- 30106151
TI  - [Retracted] Combined treatment with extracorporeal shock-wave therapy and bone
      marrow mesenchymal stem cell transplantation improves bone repair in a rabbit
      model of bone nonunion.
AB  - The authors of the above article wish to retract it on account of two reasons:
      First, the authors have experienced irreconcilable difficulties in deciding upon
      the suitable order of the authors in the author list. Secondly, due to the
      authors' negligence, the graph featured in Fig. 1 on p. 1328 does not match with
      the textual description, and the authors intend to rectify this discrepancy by
      performing further experiments. The authors regret any inconvenience that this
      retraction has caused. [the original article was published in Molecular Medicine
      Reports 17: 1326-1332, 2018; DOI: 10.3892/mmr.2017.7984].

PMID- 30106150
TI  - Novel prognostic biomarkers of gastric cancer based on gene expression
      microarray: COL12A1, GSTA3, FGA and FGG.
AB  - Gastric cancer (GC) is the fifth most common malignancy and the third leading
      cause of cancer-associated mortality in the world. However, its mechanisms of
      occurrence and development have not been clearly elucidated. Furthermore, there
      is no effective tumor marker for GC. Using DNA microarray analysis, the present
      study revealed genetic alterations, screened out core genes as novel markers and
      discovered pathways for potential therapeutic targets. Differentially expressed
      genes (DEGs) between GC and adjacent normal tissues were identified, followed by
      pathway enrichment analysis of DEGs. Next, the protein-protein interaction (PPI)
      network of DEGs was built and visualized. Analyses of modules in the PPI network
      were then performed to identify the functional core genes. Finally, survival
      analysis of core genes was conducted. A total of 256 genes were identified as
      DEGs between the GC samples and normal samples, including 169 downregulated and
      87 upregulated genes. Through Gene Ontology (GO) and Kyoto Encyclopedia of Genes
      and Genomes pathway enrichment analysis, the present study identified a total of
      143 GO terms and 21 pathways. Six clusters of functional modules were identified,
      and the genes associated with these modules were screened out as the functional
      core genes. Certain core genes, including collagen type 12 alpha1 chain
      (COL12A1), glutathione S-transferase alpha3 (GSTA3), fibrinogen alpha chain (FGA)
      and fibrinogen gamma chain (FGG), were the first reported to be associated with
      GC. Survival analysis suggested that these four genes, COL12A1 (P=0.002), GSTA3
      (P=3.4x10-6), FGA (P=0.00075) and FGG (P=1.4x10-5), were significant poor
      prognostic factors and therefore, potential targets to improve diagnosis,
      optimize chemotherapy and predict prognostic outcomes.

PMID- 30106152
TI  - Estrogen receptor antagonist fulvestrant inhibits proliferation and promotes
      apoptosis of prolactinoma cells by regulating the IRE1/XBP1 signaling pathway.
AB  - The aim of the present study was to evaluate the effects of an estrogen receptor
      antagonist, fulvestrant, on proliferation and apoptosis of prolactinoma cells,
      and to reveal potential regulatory mechanisms. Prolactinoma GH3 cells were
      treated with 10-6 mol/l fulvestrant for 2, 4, 8, 12 and 24 h. GH3 cell growth was
      observed under a microscope and cell viability was detected by MTT assay.
      Morphological changes of the nuclei in GH3 cells were observed by Hoechst 33258
      staining and apoptotic rates were detected by flow cytometry. Preprolactin (PPL)
      and prolactin (PRL) secretion levels from GH3 cells were measured using ELISA. In
      addition, the protein expression levels of inositol-requiring enzyme 1 (IRE1), X
      box binding protein (XBP)-1 and glucose-regulated protein, 78 kDa (GRP78) in GH3
      cells were detected by western blot analysis. Cell density and cell viability of
      GH3 cells were significantly reduced in a time-dependent manner following
      treatment with fulvestrant (P<0.05). GH3 cells treated with fulvestrant also
      acquired an apoptotic morphology and the apoptotic rate of GH3 cells was
      significantly increased by fulvestrant in a time-dependent manner (P<0.05). PPL
      and PRL secretion levels were significantly reduced by fulvestrant treatment in a
      time-dependent manner (P<0.05). The protein expression levels of IRE1, XBP1 and
      GRP78 were also significantly reduced in a time-dependent manner following
      treatment with fulvestrant (P<0.05). Therefore, fulvestrant may inhibit
      proliferation and promote apoptosis of GH3 cells by downregulating the IRE1/XBP1
      signaling pathway.

PMID- 30106153
TI  - Correlation between DEC1/DEC2 and epithelial-mesenchymal transition in human
      prostate cancer PC-3 cells.
AB  - Differentiated embryonic chondrocyte (DEC) genes have been reported to be
      involved in the regulation of mammalian circadian rhythms, differentiation,
      apoptosis, the response to hypoxia and epithelial-mesenchymal transition (EMT).
      Activation of transforming growth factor (TGF)-beta signaling is known to promote
      EMT for the development of metastatic castration-resistant prostate cancer (PCa).
      However, the role of DEC genes in the TGF-beta-induced EMT of PCa remains
      unclear. In the present study it was demonstrated that TGF-beta increased the
      transcriptional/translational levels of DEC1 but decreased those of DEC2 in PC-3
      cells. Moreover, TGF-beta evoked the phosphorylation of Smad2, followed by the
      activation of mesenchymal markers, such as N-cadherin and vimentin, in addition
      to the suppression of epithelial markers, such as E-cadherin. The knockdown of
      DEC1 restrained TGF-beta-induced cell morphology changes as well as cell
      motility, which was compatible with the upregulation of E-cadherin and
      downregulation of pSmad2, N-cadherin, and vimentin. However, DEC2 knockdown
      endorsed PC-3 cells with a more metastatic phenotype. EMT-related markers in DEC2
      siRNA-transfected cells exhibited a reverse expression pattern when compared with
      that in DEC1 siRNA-transfected cells. Taken together, these results provide
      evidence that DEC1 and DEC2 have opposite effects on TGF-beta-induced EMT in
      human prostate cancer PC-3 cells.

PMID- 30106154
TI  - Cell-to-cell communication via extracellular vesicles among human pancreatic
      cancer cells derived from the same patient.
AB  - Despite existing multimodal therapies, pancreatic cancer exhibits high metastatic
      capability and poor prognosis. Extracellular vesicles (EVs) are nanoparticles
      comprising lipid bilayers and various other components, such as protein and
      nucleic acids, derived from secreted cells. Recent research has demonstrated the
      involvement of EVs released from cancer cells in the metastasis of cancer cells
      to distant organs. However, the effects of EVs released from pancreatic cancer
      cells on other pancreatic cancer cells in a tumor microenvironment remain
      unclear. The present study aimed to elucidate that EVs released from PK-45H
      pancreatic cancer cells are taken up by PK-45P pancreatic cancer cells derived
      from the same patient through dynamin-related endocytosis. Additionally, EVs
      released from PK-45H cells augment the phosphorylation of classical mitogen
      activated protein kinase (MAPK) pathways in PK-45P cells. The uptake of EVs
      released from PK-45H cells by PK-45P cells stimulates cell migration through the
      classical MAPK-dependent pathway, suggesting that EVs released from one
      pancreatic cancer cell are taken up by other surrounding pancreatic cancer cells
      and could be critical inducers of cancer metastasis in the tumor
      microenvironment.

PMID- 30106156
TI  - Immune thrombocytopenia induces autophagy and suppresses apoptosis in
      megakaryocytes.
AB  - Immune thrombocytopenia (ITP) is the main pathogenesis of excessive platelet
      destruction and abnormal megakaryocyte apoptosis, however, the mechanism
      underlying this abnormality in megakaryocytes remains to be elucidated. Since
      autophagy and apoptosis are closely interrelated, it can be speculated that the
      abnormal apoptosis of ITP megakaryocytes is associated with autophagy. To test
      this hypothesis, a total of 14 patients with ITP and 23 healthy controls were
      recruited. MEG-01 cell line was cultured in vitro, and morphological changes were
      observed by light microscopy, apoptosis was evaluated by flow cytometric analysis
      of Annexin V-FITC/propidium iodide staining and western blot analysis of B-cell
      lymphoma (Bcl)-2, Bcl-associated X protein (Bax), Beclin-1 and cleaved caspase 3.
      Apoptotic abnormalities and autophagy were observed in the ITP plasma group.
      Furthermore, Bax expression was downregulated, while Beclin-1 was upregulated.
      Chloroquine can block autophagy induced by ITP and remove the ITP plasma
      inhibition of apoptosis. Therefore, it may be concluded that ITP may induce
      autophagy, the inhibition of which may be a novel treatment for ITP.

PMID- 30106157
TI  - Salmon cartilage proteoglycan attenuates allergic responses in mouse model of
      papain-induced respiratory inflammation.
AB  - Proteoglycan (PG) is a complex glycohydrate, which is widely distributed in the
      extracellular matrix. It has been reported that daily oral administration of PG
      (extracted from salmon nasal cartilage) modulates the severity of proinflammatory
      cytokine responses in mouse experimental colitis, autoimmune encephalomyelitis,
      collagen-induced arthritis and obesity-induced inflammation. The present study
      investigated the effect of salmon nasal cartilage PG on allergic responses using
      a mouse model of papain-induced respiratory inflammation. Low titers of
      immunoglobulin E were identified in the sera of the PG-administered mice. Oral
      administration of PG attenuated eosinophil infiltration in the lung. In the acute
      model of papain-induced allergic inflammation, PG-administered mice exhibited low
      titers of epithelium-derived and T helper 2-associated cytokines. The results of
      the present study demonstrated that salmon cartilage PG has an immunomodulatory
      effect on intranasally delivered papain. These results suggest a potential role
      for PG as a prophylactic agent which may attenuate allergic respiratory
      inflammation.

PMID- 30106155
TI  - MicroRNA-675-3p promotes esophageal squamous cell cancer cell migration and
      invasion.
AB  - Esophageal cancer ranks fourth in cancer-associated mortality in China and the
      incidence of esophageal adenocarcinoma has risen dramatically over the past two
      decades. MicroRNA (miRNA/miR) serves a pivotal role in human cancer cell growth,
      invasion and migration. MiR-675-3p is highly expressed in esophageal squamous
      cell cancer (ESCC) tissues, and may have an influence on ESCC cell migration and
      invasion. ESCC tumor tissue samples from 35 patients were profiled. MiR-675-3p
      expression was confirmed by reverse transcription-quantitative polymerase chain
      reaction. Manipulation of miR-675-3p via knockdown was carried out with
      subsequent evaluation of effects on cell proliferation, invasion, migration, and
      use of western blotting and ELISA assays. MiR-675-3p was overexpressed in ESCC
      tissues compared with normal tissues, and had higher expression levels in ESCC
      cells compared with the healthy esophageal epithelial cell line. The results
      revealed a predominant upregulation of cell migration and invasion ability. MiR
      675-3p inhibitor inhibited ESCC cell proliferation, migration and invasion
      ability. It was also demonstrated that downregulation of miR-675-3p decreased the
      levels of matrix metalloproteinase (MMP) 2 and 9 and increased the level of E
      cadherin. In addition, the effects of miR-675-3p inhibitor on ESCC cell lines
      were eliminated by con-transfection with miR-675-3p inhibitor and miR-675-3p
      mimic. In conclusion, the results indicated that miR-675-3p may be involved in
      the progression of ESCC through regulating ESCC cell migration and invasion
      capacity via modulating epithelial mesenchymal transition markers (MMP2, MMP 9
      and E-cadherin).

PMID- 30106158
TI  - Sinomenine alleviates dextran sulfate sodium-induced colitis via the Nrf2/NQO-1
      signaling pathway.
AB  - Sinomenine (SIN), a pure alkaloid isolated from Sinomenium acutum, has been
      widely used in arthritis for its anti-inflammatory effect, but little is known
      about the effect of SIN on human ulcerative colitis (UC). In the present study,
      the effect and mechanism of SIN was examined in a dextran sulfate sodium (DSS)
      induced murine colitis model, which mimics human UC. Oral administration of SIN
      significantly suppressed the elevated disease activity index and ameliorated
      colonic histological damage in a DSS-induced colitis model. Tumor necrosis factor
      alpha, interleukin-6 and inducible nitric oxide synthase levels were also reduced
      as detected by reverse transcription-quantitative polymerase chain reaction. In
      addition, SIN reversed the decreased colon length and colonic superoxide
      dismutase activity. Furthermore, western blot analysis revealed that nuclear
      factor-erythroid 2-related factor 2 (Nrf2) and its downstream genes, heme
      oxygenase-1 and NADP(H) quinone oxidoreductase 1 (NQO-1), were markedly activated
      by SIN. The current results indicated that SIN alleviated DSS-induced colitis in
      mice, which may be due to its antioxidant properties and was at least in part
      dependent on the Nrf2/NQO-1 signaling pathway. Therefore, SIN may have potential
      applications as a protective drug for patients with UC.

PMID- 30106159
TI  - MicroRNA-342-3p suppresses proliferation and invasion of nasopharyngeal carcinoma
      cells by directly targeting Cdc42.
AB  - Deregulated microRNAs play an important role in the development and progression
      of various types of cancer. In our previous study, we observed that microRNA-342
      3p (miR-342-3p) was one of the most markedly downregulated microRNAs in two
      nasopharyngeal carcinoma (NPC) cell lines compared to non-neoplastic cells by
      using whole genome small RNA sequencing. In the present study, we confirmed that
      the expression of miR-342-3p was significantly reduced in NPC tissues compared
      with normal nasopharyngeal epithelial tissues. Overexpression of miR-342-3p
      inhibited proliferation, epithelial-mesenchymal transition (EMT), migration and
      invasiveness of NPC cells. In addition, we observed that Cdc42, a Rho GTPase
      family member involved in cell proliferation and metastasis, is a direct target
      of miR-342-3p. Additionally, ML141, a small-molecule inhibitor of Cdc42,
      efficiently suppressed the invasion of NPC cells compared with the control cells.
      Finally, we analyzed NPC tissues derived from 10 NPC patients and subjected them
      to quantitative RT-PCR and immunohistochemistry assays for concomitant
      determination of the expression levels of miR-342-3p and Cdc42. Our results
      revealed that miR-342-3p levels were significantly inversely correlated with the
      protein levels of its target Cdc42. The results of the present study indicated
      that miR-342-3p inhibited NPC tumor growth and invasion by directly targeting the
      Cdc42 pathway.

PMID- 30106162
TI  - Self-admission in psychiatry: The ethics.
AB  - Self-admission to inpatient treatment is a novel approach that aims to increase
      agency and autonomy for patients with severe psychiatric illness and a history of
      high utilization of inpatient care. By focusing on brief, preventive hospital
      admissions in times of increased risk of relapse, self-admission seeks to reduce
      the need for prolonged episodes of inpatient treatment. Participants are
      generally satisfied with the model, which is not surprising given that self
      admission programs allocate a scarce resource-hospital beds-to a select group.
      However, the patients targeted by these programs are not necessarily those in
      most need of hospital admission, which may compromise the commonly accepted
      'principle of need' in allocation of public healthcare resources. In light of the
      current lack of consistent evidence of the usefulness and cost-effectiveness of
      the model, several aspects need to be further studied in order to guide any large
      scale implementation of self-admission in psychiatry.

PMID- 30106160
TI  - Transcriptome and methylome profiling in a rat model of irritable bowel syndrome
      induced by stress.
AB  - Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is
      associated with psychological stress. However, the full landscape of IBS-related
      epigenetic factors remains unveiled and needs to be elucidated. The water
      avoidance stress (WAS) method was used to induce a rat IBS model. Each rat was
      monitored, and its defecation and behavior were recorded. Total colon RNA was
      isolated and subjected to Affymetrix GeneChip analysis. Reduced Representation
      Bisulfate Sequencing (RRBS) was applied to determine the genome-wide methylation
      pattern in both IBS and control rats. Rats with IBS egested a significantly
      increased amount of dry and loose stools compared with the control animals,
      without significant changes in body weight. Compared with the control group, 309
      genes were upregulated and 224 genes were downregulated in the colon of the IBS
      rats. Notch signaling and focal adhesion were increased in the differentially
      expressed genes (DEGs). A total of 541 genes had significant lower methylation
      level and 626 genes had significantly higher methylation level in their promoter
      regions. Adherens junction and leukocyte transendothelial migration were enriched
      in the differentially methylated genes (DMGs). Few genes were identified in
      common in both DEGs and DMGs, suggesting that gene expression was not altered by
      promoter methylation. Reverse transcription-quantitative polymerase chain
      reaction validation revealed that the mRNA levels of SSX2IP, PARD3 and VCL were
      significantly downregulated in the IBS group, in accordance with hypermethylation
      of their promoters. In summary, the present study used a WAS-induced IBS rat
      model to provide transcriptome and methylome profiling. Most DEGs were associated
      with Notch signaling and focal adhesion, and only a few were altered by promoter
      methylation. The present results demonstrated that psychological stress could
      influence the integrity of the intestinal mucosa barrier and regulate
      inflammatory response.

PMID- 30106161
TI  - MicroRNA-34b promotes proliferation, migration and invasion of Ewing's sarcoma
      cells by downregulating Notch1.
AB  - Ewing's sarcoma is the second most frequent bone and soft tissue sarcoma, which
      is commonly driven by the Ewing's sarcoma breakpoint region 1-friend leukemia
      integration 1 transcription factor (EWS-FLI1) fusion gene. Since microRNAs (miRs)
      can act as either oncogenes or tumor suppressor genes in human cancer, and miR
      34b has been reported to act as a tumor suppressor, the role of miR-34b in
      Ewing's sarcoma was investigated in the present study. The results demonstrated
      that miR-34b expression levels were higher in tumor samples compared within
      normal tissue samples. Notably, miR-34b expression levels were significantly
      higher in EWS-FLI1-positive samples compared within EWS-FLI1-negative samples.
      The effects of miR-34b expression on cell proliferation, migration and invasion
      were also examined. miR-34b expression was inhibited using small interfering
      (si)RNA targeting the fusion gene. Transfection of a miR-34b precursor sequence
      into siRNA-treated tumor cells resulted in a significant increase in cell growth,
      migration and invasion compared within the control group. In addition, the
      adhesive ability was increased in the Ewing's sarcoma cell line RD-ES, but not
      A673, following miR-34b upregulation. Conversely, downregulation of miR-34b
      expression led to a significant decrease in cell growth, migration and invasion.
      Notch has previously been reported to serve either oncogenic or tumor suppressive
      roles in human cancer. The results indicated that Notch1 and its target genes,
      Hes family BHLH transcription factor 1 and Hes-related family BHLH transcription
      factor with YRPW motif 1, were suppressed by miR-34b directly In conclusion, EWS
      FLI1 may modulate miR-34b expression directly or indirectly, and miR-34b
      potentially has an oncogenic role in Ewing's sarcoma by downregulating Notch1.

PMID- 30106163
TI  - An ecological approach to modeling disability.
AB  - This article develops an analysis of disability according to which disabling
      conditions are properties of organisms embedded in sets of environments. We begin
      by presenting the three mainstream accounts of disability-the medical, social,
      and interactionist models-and rehearsing some known limitations. We argue that,
      because of their primary focus on etiology, all three models share, more or less
      implicitly, a problematic assumption. This is the tenet that disabilities are
      individual properties. The second part of the essay presents an "ecological"
      interpretation of disability, inspired by classic and contemporary research on
      biological niches. Our proposal preserves many insights underlying extant
      approaches, while allowing a more accurate characterization of the nature and
      experience of disability. We conclude by drawing some general implications of our
      analysis.

PMID- 30106164
TI  - Inhibiting geranylgeranyl diphosphate synthesis reduces nuclear androgen receptor
      signaling and neuroendocrine differentiation in prostate cancer cell models.
AB  - BACKGROUND: Following androgen deprivation for the treatment of advanced
      adenocarcinoma of the prostate, tumors can progress to neuroendocrine prostate
      cancer (NEPC). This transdifferentiation process is poorly understood, but
      trafficking of transcriptional factors and/or cytoskeletal rearrangements may be
      involved. We observed the role of geranylgeranylation in this process by
      treatment with digeranyl bisphosphonate (DGBP), a selective inhibitor of
      geranylgeranyl pyrophosphate synthase which blocks the prenylation of small
      GTPases such as Rho and Rab family proteins, including Cdc42 and Rac1. METHODS:
      We examined the therapeutic potential of DGBP in LNCaP, C4-2B4, and 22Rv1 cell
      culture models. Cell morphology and protein expression were quantified to observe
      the development of the neuroendocrine phenotype in androgen-deprivation and
      abiraterone-treated LNCaP models of NEPC development. Luciferase reporter assays
      were utilized to examine AR activity, and immunofluorescence visualized the
      localization of AR within the cell. RESULTS: Essential genes in the isoprenoid
      pathway, such as HMGCR, MVK, GGPS1, and GGT1, were highly expressed in a subset
      of castration resistant prostate cancers reported by Beltran et al. Under
      treatment with DGBP, nuclear localization of AR decreased in LNCaP, 22Rv1, and C4
      2B4 cell lines, luciferase reporter activity was reduced in LNCaP and 22Rv1, and
      AR target gene transcription also decreased in LNCaP. Conversely, nuclear
      localization of AR was enhanced by the addition of GGOH. Finally, induction of
      the NEPC structural and molecular phenotype via androgen deprivation in LNCaP
      cells was inhibited by DGBP in a GGOH-dependent manner. CONCLUSIONS: DGBP is a
      novel compound with the potential to reduce AR transcriptional activity and
      inhibit PCa progression to NEPC phenotype. These results suggest that DGBP may be
      used to block cell growth and metastasis in both hormone therapy sensitive and
      resistant paradigms.

PMID- 30106165
TI  - Fragmentation dynamics and loss of area of potential occupancy within the
      distribution limits of the endangered crested capuchin monkey (Sapajus robustus).
AB  - Habitat loss is one of the main threats to biodiversity. Fragmentation resulting
      from this process may restrict available habitat for primates, limiting their
      persistence in a given region. In this study, we aimed to quantify deforestation
      and fragmentation by identifying forest remnants capable of maintaining
      populations of the endangered crested capuchin monkey (Sapajus robustus) within
      its distributional limits in the states of Bahia, Espirito Santo, and Minas
      Gerais, Brazil. We used Landsat images from 1985 to 2010 to generate three time
      interval mosaics classified by natural and non-natural vegetation. We then
      calculated the size of the forest remnants and the distance of each fragment of
      natural vegetation to its nearest neighbor. Between the first (1985-1990) and
      second (1995-2000) mosaics there was a vegetation loss of 41.4%, and between the
      second and third (2005-2010) mosaics there was a natural vegetation gain of 1%.
      The third mosaic showed smaller and more isolated fragments in comparison to the
      first mosaic. Across the three periods, Bahia was the state with the highest rate
      of deforestation. While Espirito Santo had fewer identified forest remnants, it
      retained the most natural vegetation within these small fragments. The landscape
      within the currently recognized distributional limits of the crested capuchin
      monkey is dominated by agriculture and livestock. Both decreasing fragment size
      and increasing species isolation by distance between fragments can negatively
      affect primate populations, increasing their risk of extinction. Isolation makes
      it difficult for migration and recolonization events to occur. Therefore, habitat
      restoration should be prioritized to reduce isolation between populations. Our
      findings may serve as a resource for future conservation efforts and management
      of the crested capuchin monkey.

PMID- 30106166
TI  - Insulin resistance and beta-cell dysfunction and the relationship with cardio
      metabolic disorders among women with polycystic ovary syndrome.
AB  - OBJECTIVE: To investigate both independent and combined effects of insulin
      resistance and beta-cell dysfunction on cardio-metabolic abnormalities in
      polycystic ovary syndrome (PCOS). DESIGN: A national epidemiologic survey was
      performed in reproductive aged females in China from October 2007 to September
      2011. METHODS: A total of 824 PCOS and 2715 non-PCOS were included. The Rotterdam
      Criteria were applied for PCOS diagnosis. We used the homeostasis model
      assessment of insulin resistance (HOMA-IR) and HOMA of beta-cell function (HOMA
      beta) to evaluate insulin resistance and beta-cell dysfunction, respectively.
      RESULTS: Compared with non-PCOS, PCOS showed a higher index of HOMA-IR and HOMA
      beta, and a higher prevalence of obesity, central obesity, and dyslipidaemia.
      High HOMA-IR was independently related to a high prevalence of obesity, central
      obesity, dyslipidaemia, and high blood glucose in PCOS. In contrast, a low index
      of HOMA-beta index was independently correlated with a low prevalence of obesity,
      and central obesity, but negatively correlated with an elevated prevalence of
      high blood glucose in PCOS. In addition, proportion of insulin resistance was
      higher than that of beta-cell dysfunction in PCOS with cardio-metabolic
      disorders. beta-cell dysfunction was negatively correlated with the prevalence of
      central obesity and obesity. CONCLUSIONS: Insulin resistance and beta-cell
      dysfunction independently affected cardio-metabolic abnormalities in PCOS, while
      insulin resistance was correlated with a higher prevalence of cardio-metabolic
      abnormalities than that of beta-cell dysfunction. Moreover, beta-cell dysfunction
      and insulin resistance showed divergent correlations with obesity in PCOS.

PMID- 30106167
TI  - Maintenance of bone mass despite estrogen depletion in female common marmoset
      monkeys (Callithrix jacchus).
AB  - Estrogen depletion leads to bone loss in almost all mammals with frequent regular
      ovarian cycles. However, subordinate adult female common marmosets (Callithrix
      jacchus) undergo socially induced anovulation and hypoestrogenism without
      clinically apparent adverse skeletal consequences. Thus, we speculated that this
      non human primate might have evolved a mechanism to avoid estrogen-depletion bone
      loss. To test this possibility, we performed three experiments in which lumbar
      spine (L5-L6) bone mineral content (BMC) and density (BMD) were assessed using
      dual-energy X-ray absorptiometry: (i) cross-sectionally in 13 long-term
      ovariectomized animals and 12 age- and weight-matched controls undergoing
      ovulatory cycles; (ii) longitudinally in 12 animals prior to, 3-4 and 6-7 months
      following ovariectomy (ovx), and six controls; and (iii) cross-sectionally in
      nine anovulatory subordinate and nine dominant females. In Experiments 1 and 3,
      plasma estradiol and estrone concentrations were measured and uterine dimensions
      were obtained by ultrasound in a subset of animals as a marker of functional
      estrogen depletion. Estrogen levels, uterine trans-fundus width, and uterine
      dorso-ventral diameter were lower in ovariectomized and subordinate females than
      in those undergoing ovulatory cycles. However, no differences were found in L5-L6
      BMC or BMD. These results indicate that estrogen depletion, whether surgically or
      socially induced, is not associated with lower bone mass in female common
      marmosets. Thus, this species may possess unique adaptations to avoid bone loss
      associated with estrogen depletion.

PMID- 30106168
TI  - Effects of aggressive temperament on endogenous oxytocin levels in adult titi
      monkeys.
AB  - Coordination of oxytocin (OT) activity and partner interactions is important for
      the facilitation and maintenance of monogamous pair bonds. We used coppery titi
      monkeys (Callicebus cupreus) to identify the effects of male aggressive
      temperament on OT activity, affiliative partner-directed behaviors, aggressive
      partner-directed behaviors, anxiety-related behaviors, and hormone-behavior
      interactions. We used a mirror technique, simulating an intruder in the home
      territory of pairs to elicit behavioral responses, and quantified behaviors using
      an established ethogram. Plasma concentrations of OT (pg/ml) were quantified
      using enzyme immunoassay. We used general linear mixed models to predict 1)
      percent change in OT as a function of aggression score, and 2) percent change in
      behaviors as a function of aggression, OT, and OT by aggression interactions.
      High-aggressive males exhibited a significant drop in OT concentration relative
      to control when exposed to the front of the mirror (beta = -0.22, SE = 0.10, t = 
      2.20, p = 0.04). High-aggressive males spent significantly less time in contact
      with their mates (beta = -1.35, SE = 0.60, t = -2.26, p = 0.04) and lip-smacked
      less (beta = -1.02, SE = 0.44, t = -2.32, p = 0.03) relative to control. We also
      saw a trend toward an interaction effect between OT and proximity such that High
      aggressive males displaying a drop in OT exhibited a smaller percent increase in
      social proximity (beta = 6.80, SE = 3.48, t = 1.96, p = 0.07). Males exhibiting a
      decrease in OT also trended toward back-arching and tail-lashing less in response
      to the mirror (beta = 4.53, SE = 2.5, t = 1.82, p = 0.09). To our knowledge, this
      is the first empirical study to examine interactions between OT and temperament
      in adult monogamous primates. Future studies should incorporate measures of pair
      mate interactions and early-life experience to further understand variation in
      responses to social stressors and their effects on pair bonding.

PMID- 30106169
TI  - Mechanistic reasoning and informed consent.
AB  - Evidence-based medicine (EBM) proponents have argued that mechanistic evidence
      concerning medical treatments should be considered secondary to evidence derived
      from randomized controlled trials (RCTs). One common criticism of RCTs is that
      they often do not yield results that are generalizable to clinical practice, and
      that for clinical practice application, mechanistic evidence is needed. However,
      proponents of EBM have argued that mechanistic reasoning is often unreliable and
      thus not very useful. Here we suggest an important role of mechanistic
      explanation that has been left out of this discussion entirely, namely, its
      importance in a patient's decision of whether or not to take certain drugs. We
      argue that in certain cases, knowing how a treatment works is just as important
      for the patient as knowing whetherit does. In this paper, we explore how and why
      giving patients mechanistic information can be an important factor in obtaining
      informed consent for medical treatment, focusing on the example case of hormonal
      contraceptives.

PMID- 30106170
TI  - Oesophagectomy with or without supraclavicular lymphadenectomy after neoadjuvant
      treatment for squamous cell carcinoma of the oesophagus.
AB  - BACKGROUND: Treatment of supraclavicular nodes remains controversial among
      patients with oesophageal squamous cell carcinoma. This study assessed the
      outcomes of patients who underwent oesophagectomy with or without supraclavicular
      lymphadenectomy after neoadjuvant treatment. METHODS: This was a single-centre
      retrospective cohort study. Patients with oesophageal squamous cell carcinoma and
      clinically negative supraclavicular nodes who underwent oesophagectomy after
      neoadjuvant treatment between January 2005 and December 2015 were included.
      Overall and relapse-free survival were compared between patients who did or did
      not undergo supraclavicular nodal dissection. Propensity score matching was used
      to correct for differences in prognostic factors between the groups. RESULTS:
      Some 223 patients underwent supraclavicular lymphadenectomy. The prevalence of
      pathologically confirmed supraclavicular metastasis was 10.3 per cent, and these
      patients had poor 5-year relapse-free (7 per cent) and overall (14 per cent)
      survival. Only two of 55 patients who did not undergo supraclavicular
      lymphadenectomy had recurrent disease in the supraclavicular region without
      distant metastasis. There was no statistically significant difference between the
      groups in relapse-free survival (hazard ratio (HR) 0.95, 95 per cent c.i. 0.61 to
      1.47; P = 0.821) or overall survival (HR 0.86, 0.52 to 1.40; P = 0.544).
      Similarly, no significant difference in relapse-free or overall survival was
      observed between the propensity score-matched groups. CONCLUSION: For patients
      with clinically negative supraclavicular lymph nodes, prophylactic
      supraclavicular lymphadenectomy may be omitted when neoadjuvant treatment is
      administered.

PMID- 30106171
TI  - Return to childhood? Against the infantilization of people with dementia.
AB  - The idea that dementia is essentially a return to childhood and those affected
      must somehow be similar to children constitutes a deeply rooted and pervasive
      cultural trope. While such tropes may be helpful in making sense of an otherwise
      elusive and inscrutable state, they can at the same time promote inadequate
      understandings of dementia and hence also influence our attitudes and behaviour
      towards those affected in several problematic ways. In the present work, we
      provide a detailed account of the origins and implications of the idea that
      people with dementia are somehow similar to children. In order to spell out the
      normative significance of this trope and to analyse its shortcomings, we will
      rely on a life-course perspective. We will point out that the second-childhood
      trope does not do justice to the particularities of the life phases of both
      children and people with dementia. This lack of biographical sensitivity brings
      about undignified treatment of and harm to those who have previously lived more
      autonomous lives. In conclusion, we will argue that people with dementia should
      not be equated with children as they are at a different point in their lives.
      This critical analysis of the second-childhood trope shows the usefulness of a
      culturally and biographically sensitive theoretical framework for bioethical
      reflection. In particular, it provides reasons to reject infantilizing attitudes
      and behaviours and instead take seriously the personality, values and preferences
      shaped throughout the course of an individual's life.

PMID- 30106172
TI  - Measures of Functioning in Patients With Episodic Migraine: Findings From a
      Double-Blind, Randomized, Placebo-Controlled Phase 2b Trial With Galcanezumab.
AB  - Objective - To evaluate 12-week changes from baseline of 2 disease-specific
      patient-reported outcome (PRO) measures in adults with migraine treated with
      galcanezumab, an investigational humanized antibody binding calcitonin gene
      related peptide (CGRP), or placebo. Background - Preventing headache-related
      functional impairment is an important goal of migraine preventive treatment and a
      measurement target for PROs. Understanding which drugs have the potential to
      improve patient functioning in addition to preventing migraine headaches is vital
      to lessening patient burden. Design/Methods - This Phase 2b double-blind,
      randomized, placebo-controlled study enrolled adults with episodic migraine.
      Galcanezumab (120 mg subcutaneous injection; n = 60) or placebo (n = 127) was
      administered every 28 days for 12 weeks. Post hoc secondary analyses were
      conducted for those who completed 12 weeks of treatment on 2 PROs: The Migraine
      Specific Quality of Life Questionnaire (MSQ) v2.1 and the Headache Impact TestTM
      (HIT-6). Results - Analysis of covariance revealed significant differences in
      least square mean changes from baseline between galcanezumab and placebo for all
      MSQ domains including total mean change placebo of 18.63, galcanezumab of 27.36
      (95% CI 2.449, 15.008; P-value of .0067); Role Function-Restrictive mean change
      placebo of 22.40, galcanezumab of 31.92 (95% CI 2.636, 16.518; P-value of .0071);
      Role Function-Preventive mean change placebo of 13.43, galcanezumab of 19.76 (95%
      CI 0.476, 12.185; P-value of .0342); and Emotional Function mean change placebo
      of 16.88, galcanezumab of 26.61 (95% CI 2.789, 16.674; P-value of .0063). At
      baseline, mean number of migraine headache days (MHDs) did not correlate with MSQ
      total scores or HIT-6. At 12 weeks post-treatment, MHD correlated with MSQ and
      HIT-6 scores (all P < .0001). Change in MHD was associated with change in MSQ
      domains and change in HIT-6 scores (all P < .0001). Conclusions - In comparison
      with placebo, treatment with galcanezumab was associated with significant
      functional improvements as reflected by changes in MSQ scores. Change in MHD was
      associated with improvements in MSQ and reductions in HIT-6 scores, indicating
      the clinical importance of these changes in relation to PROs that measure
      function.

PMID- 30106174
TI  - PPIENSENLo: A Novel Mnemonics in Spanish for Alarm Criteria in Secondary
      Headaches in Children.
AB  - We present the first mnemonic in Spanish, "PPIENSENLo," for alarm criteria in
      secondary headaches in children in order to facilitate their identification,
      diagnosis, and treatment. A search was performed across different electronic
      databases for a mnemonics that applied to clinical alarm criteria in secondary
      headaches in children. None were found in English or Spanish. This tool is
      perhaps useful both for clinical and teaching purposes.

PMID- 30106173
TI  - Modified back-projection method in acoustic resolution-based photoacoustic
      endoscopy for improved lateral resolution.
AB  - PURPOSE: Acoustic resolution photoacoustic endoscopy (ARPAE) is an emerging tool
      for gastrointestinal tract and esophagus imaging. However, high resolution over
      large depth of field in ARPAE is still a challenge to be addressed due to the
      usage of fixed-focus transducers. METHODS: To solve this problem, a modified back
      projection reconstruction algorithm is proposed in this work, which was
      demonstrated in two dimensions (2D). By employing data from multiple transducer
      positions and at the meantime considering the geometry of the transducer
      detection surface, this method offers a significantly improved lateral resolution
      throughout the imaging depth. The proposed method was evaluated with extensive
      numerical simulations and phantom experiments. RESULTS: Numerical simulations
      showed that the depth of focus (DOF) is greatly improved with our proposed
      method. Results also indicated that the improvement of the lateral resolution is
      more notable when the transducer has larger numerical aperture (NA) and higher
      central frequency, and the transducer focus is placed further from the rotation
      center. Experimental data further indicate there is a 30% to 40% improvement in
      the lateral resolution of targets in the out-of-focus region with our proposed
      new method. CONCLUSION: This work can readily be employed in most current ARPAE
      systems to improve the obtained image quality, and may promote the advancement of
      ARPAE toward clinical applications.

PMID- 30106176
TI  - Is infertility a disease and does it matter?
AB  - Claims about whether or not infertility is a disease are sometimes invoked to
      defend or criticize the provision of state-funded treatment for infertility. In
      this paper, I suggest that this strategy is problematic. By exploring infertility
      through key approaches to disease in the philosophy of medicine, I show that
      there are deep theoretical disagreements regarding what subtypes of infertility
      qualify as diseases. Given that infertility's disease status remains unclear, one
      cannot uncontroversially justify or undermine its claim to medical treatment by
      claiming that it is or is not a disease. Instead of focusing on disease status, a
      preferable strategy to approach the debate about state-funded treatment is to
      explicitly address the specific ethical considerations raised by infertility. I
      show how this alternative strategy can be supported by a recent theoretical
      framework in the philosophy of medicine which avoids the problems associated with
      the concepts of health and disease.

PMID- 30106178
TI  - Parents' posthumous use of daughter's ovarian tissue: Ethical dimensions.
AB  - In recent years, progress in cancer treatment has greatly increased the chances
      of recovery. Yet, treatment may have irreversible effects on patients' fertility.
      In order to protect future fertility, preservation of ovarian tissue may be
      offered today even to very young girls, involving a surgical procedure that may
      be performed by minimally invasive laparoscopy, under general anesthesia.
      However, in the tragic event of a girl's death, questions may arise regarding the
      possible use of the preserved ovarian tissue by her parents. Should posthumous
      reproductive use of ovarian tissue without the girl's prior consent (due to her
      young age) be considered a violation of her rights? On the other hand, can it be
      argued that it is in the interest of a child who died young to leave a genetic
      trace through posthumous reproduction, because genetic continuity is in the
      interest of every human being? After presenting the relevant clinical facts, we
      explore the ethical dimensions of this possible practice through an analysis of
      the interests of the deceased, her parents, and the child that may be born
      posthumously.

PMID- 30106177
TI  - Subspecies differentiation and genotyping of Francisella tularensis strains
      isolated from clinical and environmental samples.
AB  - Molecular epidemiology is one of the most rapidly developing research area. In
      the light of past and modern technologies it has gained number of typing methods
      based on molecular biology techniques. In this report, the subspecies
      differentiation of Francisella tularensis and genotyping of strains isolated in
      Poland and other geographic locations were investigated using real-time PCR and
      multispacer typing (MST) methods respectively. In total, 49 strains of F.
      tularensis included 15 strains from Poland, for subspecies differentiation the
      real-time PCR method was applied. For molecular typing using MST method four
      intergenic spacers (IS) were sequenced and compared with those previously
      described and deposited in GenBank (NCBI). Phylogenetic testing was performed
      using with the UPGMA model using MEGA6 software. The real-time PCR enables to
      distinguish five strains belonged to type A and 44 to type B among deposited F.
      tularensis strains. The MST revealed previously described genotypes, as well as
      23 new genotypes were detected. The use of real-time PCR and MST method are
      valuable in the analysis of F. tularensis. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study demonstrate convenient molecular tools (real-time PCR and multispacer
      typing) for Francisella tularensis detection, differentiation and genotyping
      which can be applied for molecular epidemiological studies and providing useful
      information for scientific research and during natural tularaemia outbreaks.

PMID- 30106179
TI  - Sexual Passion in Committed Relationships: Measurement and Conceptual Issues.
AB  - The purpose of this study is to discuss the need for a new triadic model of
      sexual passion in relationships and to present the preliminary psychometric
      properties of a scale designed to measure these three approaches to passion
      (harmonious, obsessive, and inhibited) for use in clinical and scholarly work.
      Existing theory and measures of general passion are based on a dualistic model of
      passion that includes the harmonious and obsessive approaches to passion. We
      added the inhibited approach to passion from the sexuality research and develop
      measures for assessing sexual passion in relationships. We utilized an Amazon
      Mechanical Turk sample of 1,421 individuals in committed relationships to test
      this measure. Reliability analyses and confirmatory factory analyses evinced that
      these three approaches to sexual passion were unique constructs and distinct from
      sexual satisfaction. Sexual passion showed predictive validity above and beyond
      relationship length, sexual desire toward a partner, and a broader variable of
      sexual drive. Harmonious sexual passion robustly predicted higher sexual
      satisfaction and relationship satisfaction, and inhibited sexual passion
      moderately predicted lower sexual satisfaction and relationship satisfaction.
      Obsessive sexual passion had minimal associations with either outcome. These new
      constructs, especially harmonious and inhibited sexual passion, may help scholars
      and practitioners improve their understanding of sexual satisfaction and overall
      relationship satisfaction.

PMID- 30106180
TI  - Theoretical investigation of the count rate capabilities of in-pixel amplifiers
      for photon counting arrays based on polycrystalline silicon TFTs.
AB  - PURPOSE: Photon counting arrays (PCAs), capable of measuring the spectral
      information of individual x-ray photons and recording that information digitally,
      provide a number of advantages compared to conventional, energy-integrating
      active matrix flat-panel imagers - such as reducing the undesirable effects of
      electronic readout noise and Swank noise. While contemporary PCAs are based on
      crystalline silicon, our group has been examining the use of polycrystalline
      silicon (poly-Si, a semiconductor material better-suited for the manufacture of
      large-area devices) for such arrays. In this study, a theoretical investigation
      of the front-end amplifiers of array pixels incorporating photon counting
      circuits is described - building upon circuit simulation techniques developed in
      a previous study. Results for amplifier circuit designs corresponding to
      prototype PCAs currently under development, as well as for hypothetical circuit
      designs identified in the study, are reported. In the simulations, performance
      metrics (such as signal gain, linearity of signal response, and energy
      resolution) as well as various measures of count rate are determined. METHODS:
      The simulations employed various input energy distributions (i.e., a 72 kVp
      spectrum as well as monoenergetic x rays) in order to determine circuit
      performance. To make the results representative of the properties of poly-Si, the
      simulations incorporated transistor characteristics that were empirically
      obtained from test devices. Optimal operating conditions for the circuits were
      determined by applying criteria to the performance metrics and identifying which
      conditions minimized settling time. Once the optimal operating conditions were
      identified, trains of input pulses simulating x-ray flux were used to determine
      two measures of count rate corresponding to dead time losses of 10% and 30%
      (referred to as CR10 and CR30 , respectively). RESULTS: The best-performing
      prototype amplifier design (implemented at a pixel pitch of 1 mm) exhibited CR10
      and CR30 values (expressed in counts per second per pixel) of 8.4 and 21.6
      kcps/pixel, respectively. A hypothetical amplifier design was derived by
      modifying transistor, resistor, and capacitor elements of the prototype amplifier
      designs. This hypothetical design (implemented at a pitch of 1 mm) exhibited CR10
      and CR30 values of 154 and 381 kcps/pixel, respectively. When implemented at a
      pitch of 0.25 mm, the performance of that design increased to 210 and 491
      kcps/pixel, respectively (corresponding to counts per second per unit area of 3.4
      and 7.9 Mcps/mm2 ). CONCLUSIONS: The simulation methodology described in this
      paper represents a useful tool for identifying promising designs for the
      amplifier component of photon counting arrays, as well as evaluating the analog
      signal and noise performance of those designs. The results obtained from the
      current study support the hypothesis that large-area, photon counting arrays
      based on poly-Si transistors can provide clinically useful count rates.
      Encouraged by these early results, further development of the methodology to
      assist in the identification and evaluation of even more promising designs, along
      with development and empirical characterization of prototype designs, is planned.

PMID- 30106181
TI  - Mesenchymal COX2-PG secretome engages NR4A-WNT signalling axis in haematopoietic
      progenitors to suppress anti-leukaemia immunity.
AB  - The bone marrow (BM) microenvironment (niche) plays important roles in supporting
      normal/abnormal haematopoiesis. We investigated the interaction between leukaemic
      mesenchymal niche and haematopoietic stem and progenitor cells (HSPCs) using the
      model of Fanconi anaemia (FA), a genetic disorder characterized by BM failure and
      leukaemia. Healthy donor HSPCs co-cultured on mesenchymal stromal cells (MSCs)
      derived from FA patients with acute myeloid leukaemia (AML) exhibited higher
      human engraftment and myeloid expansion in Non-obese diabetic severe combined
      immunodeficiency IL-2gamma-/- /SGM3 recipients. Untargeted metabolomics analysis
      revealed the progressively elevated prostaglandins (PGs) in the MSCs of FA
      patients with myelodysplastic syndromes (MDS) and AML. Reduced secretion of PGs
      subsequent to inflammatory cyclooxygenase 2 (COX2) inhibition ameliorated
      HSPC/myeloid expansion. Transcriptome analysis demonstrated dysregulation of
      genes involved in the NR4A family of transcription factors (TFs) and WNT/beta
      catenin signalling pathway in FA-AML-MSC-co-cultured-CD34+ cells. COX2 inhibition
      led to significantly decreased NR4A TFs and WNT signalling genes expression.
      Mechanistically, NR4A1 and NR4A2 synergistically activate the CTNNB1 gene
      promoter . Knocking down CTNNB1 or NR4A1 in AML-MSC-co-cultured-CD34+ cells
      increased leukaemia-reactive T-effector cells production and rescued anti
      leukaemia immunity. Together, these findings suggest that specific interactions
      between leukaemic mesenchymal niche and HSPCs orchestrate a novel COX2/PG
      NR4A/WNT signalling axis, connecting inflammation, cellular metabolism and cancer
      immunity.

PMID- 30106182
TI  - Colour Doppler ultrasound imaging of blood flows variations in neoplastic and non
      neoplastic testicular lesions in dogs.
AB  - Testicular tumours are the most common neoplasms in male dogs accounting for
      approximately 90% of all tumours affecting the genitourinary tract. Gray-scale
      ultrasonography in combination with colour and power Doppler imaging has been
      well accepted as an accurate technique for assessing scrotal lesions and
      vascularization of the testis. Colour Doppler sensitivity for low blood flows
      appears promising in the study of testicular disorders. The aim of this study was
      to assess if colour and power Doppler ultrasound is a good tool for the
      investigation of testicular lesions in dogs, to report the sonographic features
      of lesions and to measure colour and power Doppler parameters such as resistive
      index (RI), pulsatility index (PI), hypovascularization and hypervascularization
      (VI) determining if they can be used to distinguish testicular neoplasms from the
      wide spectrum of non-neoplastic pathological findings. In this study, 50 male
      dogs of various breeds, aged between 7 and 14 years, presented with testicular
      disorders were selected. RI and PI were calculated. Mean RI values for
      neoplastic, inflammatory and degenerative lesions were 0.54, 0.45 and 0.58,
      respectively. Mean PI values were 0.62, 0.55 and 0.63, respectively.
      Hypovascularization and hypervascularization of the lesion were evaluated
      throughout the vascularity index (VI). Vascular signals in neoplasms were
      significantly intensified around and inside the mass if compared with those
      measured during inflammatory and degenerative lesions. VI markedly increased in
      solid tumours. Pathological testes were removed; macroscopical, histological and
      immunoistochemical evaluations were carried out. Colour Doppler showed increased
      intralesional and peripheral flows in all neoplastic lesions analysed. No flows
      were detected around cysts.

PMID- 30106183
TI  - An experimental murine model of otitis and dermatitis caused by Malassezia
      pachydermatis.
AB  - We report a malasseziosis model in immunocompromised Swiss mice. For this model,
      the mice were immunosuppressed with a combination of cyclophosphamide at 150
      mg/kg and hydrocortisone acetate at 250 mg/kg. Two groups were formed according
      to the site of inoculation. Dermatitis group received an intradermal injection of
      5 * 106 cell/mouse at a shaved dorsal region, while the otitis group received the
      same inoculum in the middle ear. Five animals/group were euthanised at different
      times, and the skin and ear were histopathologically analysed. During the first
      euthanasia, which occurred after inoculation, microscopic examination showed that
      all mice presented budding yeast-like in a tissue sample. The presence of yeasts
      decreased over time being undetected on the 17th day (dermatitis group) and the
      21st day (otitis group) after inoculation. This is the first murine model for
      malasseziosis that can be useful for evaluating new treatment approaches.

PMID- 30106184
TI  - MGL_3741 gene contributes to pathogenicity of Malassezia globosa in pityriasis
      versicolor.
AB  - Dihydroxyacid dehydratase (DHAD) is a key enzyme in biosynthetic pathway of
      isoleucine and valine. This pathway is absent in human but exists in various
      organisms such as fungi. Using RNA-seq analysis in this study, we identified
      MGL_3741gene which encodes DHAD protein in Malassezia globosa (M. globosa).
      Furthermore, we found that mentioned gene is homologous to the Ustilago maydis,
      Saccharomyces cerevisiae, Aspergillus flavus, and Aspergillus fumigatus ILV3P.
      For understanding the probable role of this gene in pathogenicity of M. globosa,
      we applied Real-time PCR to investigate the differentially expressed of the
      MGL_3741 gene in healthy and pathogenic states. Our results indicate a
      significant difference between two mentioned stats. These results revealed that
      ILV3-like gene in M. globosa can be related to the pathogenicity of this yeast.

PMID- 30106185
TI  - Long-term cardiovascular outcome of renal transplant recipients after early
      conversion to everolimus compared to calcineurin inhibition: results from the
      randomized controlled MECANO trial.
AB  - Long-term data on cardiovascular (CV) outcome of renal transplant recipients
      (RTR) on mTOR-i (mammalian Target Of Rapamycin-inhibitors) are scarce. In a sub
      study of the MECANO trial we investigated changes in intima media thickness
      (IMT), CV risk profile, Major Adverse CV Events (MACE) and survival in RTR on a
      mTORi versus CNI based regimen. Patients (enrolled 361) were treated with
      (basiliximab) and triple IS (CsA-Cyclosporine A-(C), MPS (M), prednisolone (P)).
      At M6 patients were randomized (n = 224) to the CsA group (C, P, N = 89), MPS
      group (M, P, N = 39) EVL group (Everolimus, P, N = 96). At week 2, M6 and M 24,
      IMT measurements of the Common Carotid Artery were performed. Cardiovascular risk
      factors were assessed at baseline, 6 and 24 months of follow-up. Seven years
      survival and MACE-free survival probability were calculated by the Cardiovascular
      Risk Calculator for RTR. After 7 years of follow-up, incidence of cardiovascular
      events and patient survival were assessed. Mean IMT at baseline (N = 192), was
      0.64 +/- 0.14 mm. At M6 (N = 158), 0.66 +/- 0.15, M24 IMT was 0.68 +/- 0.15 (N =
      95). No significant differences between groups concerning IMT, true CV events and
      mortality, CV risk profile, predicted MACE/Mortality were found between mTORi and
      CNI-based regimen after 7 years of follow-up.

PMID- 30106186
TI  - Looping Star.
AB  - PURPOSE: To introduce a novel MR pulse sequence, termed Looping Star, for fast,
      robust, and yet quiet, 3D radial multi-gradient echo T2* MR imaging. METHODS: The
      Looping Star pulse sequence is based on the 3D radial Rotating Ultra-Fast Imaging
      Sequence (RUFIS) extended by a time-multiplexed gradient-refocusing mechanism.
      First, multiple magnetic coherences are excited, which are subsequently gradient
      refocused in form of a looping k-space trajectory. Accordingly, Looping Star
      captures an initial FID image followed by gradient echo images at equidistant
      echo times. RESULTS: Looping Star was demonstrated in phantom and in vivo
      volunteer experiments for 3D, high resolution T2* weighted imaging, T2* mapping,
      and quantitative susceptibility mapping (QSM). The method is fast, quiet, and
      robust against imperfections including Eddy currents, motion, and geometric
      distortions. When applied to a motor task fMRI experiment a BOLD sensitivity of
      5% was achieved at minimal acoustic noise (i.e. 2.7 dB(A) above ambient noise)
      and with images congruent to other anatomical scans. CONCLUSIONS: Looping Star
      imaging provides new and exciting opportunities for fast, robust and yet quiet
      T2* MR imaging. Potential applications include T2*-weighted imaging, T2* mapping,
      QSM, and fMRI.

PMID- 30106188
TI  - Loop-mediated isothermal amplification for the rapid detection of Gardnerella
      vaginalis.
AB  - The aim of this study was to develop a method for the rapid detection of
      Gardnerella vaginalis, which is proposed to play a key role in the pathogenesis
      of bacterial vaginosis. Specific loop-mediated isothermal amplification (LAMP)
      primers were designed and used to detect target DNA within 45 min under
      isothermal conditions. Comparative screening indicated that the LAMP assay is
      superior to PCR in terms of rapidity, and is equivalent in sensitivity and
      specificity. This LAMP assay can be used for rapid screening and detection of G.
      vaginalis in vaginal samples; the limit of detection is 10 fg DNA.

PMID- 30106187
TI  - The time-dependent variation of ATP release in mouse primary-cultured urothelial
      cells is regulated by the clock gene.
AB  - AIMS: The sensation of bladder fullness (SBF) is triggered by the release of ATP.
      Therefore, the aim of this study was to investigate whether time-dependent
      changes in the levels of stretch-released ATP in mouse primary-cultured
      urothelial cells (MPCUCs) is regulated by circadian rhythm via clock genes.
      METHODS: MPCUCs were derived from wild-type and Clock mutant mice
      (ClockDelta19/Delta19 ), presenting a nocturia phenotype. They were cultured in
      elastic silicone chambers. Stretch-released ATP was quantified every 4 h by ATP
      photon count. An experiment was also performed to determine whether ATP release
      correlated with the rhythm of the expression of Piezo1, TRPV4, VNUT, and
      Connexin26 (Cx26) in MPCUCs regulated by clock genes with circadian rhythms.
      MPCUCs were treated with carbenoxolone, an inhibitor of gap junction protein;
      were derived from VNUT-KO mice; or treated with Piezo1-siRNA, TRPV4-siRNA, and
      Cx26-siRNA. RESULTS: Stretch-released ATP showed time-dependent changes in wild
      type mice and correlated with the rhythm of the expression of Piezo1, TRPV4,
      VNUT, and Cx26. However, these rhythms were disrupted in ClockDelta19/Delta19
      mice. Carbenoxolone eliminated the rhythmicity of ATP release in wild-type mice.
      However, time-dependent ATP release changes were maintained when a single gene
      was deficient such as VNUT-KO, Piezo1-, TRPV4-, and Cx26-siRNA. CONCLUSIONS: ATP
      release in the bladder urothelium induces SBF and may have a circadian rhythm
      regulated by the clock genes. In the bladder urothelium, clock gene abnormalities
      may disrupt circadian ATP release by inducing Piezo1, TRPV4, VNUT, and Cx26. All
      these genes can trigger nocturia.

PMID- 30106189
TI  - Congenital vesicouterine fistulas-A PRISMA-compliant systematic review.
AB  - AIMS: Vesicouterine fistulas (VUFs) are infrequent abnormal connections between
      the bladder and the uterine cavity or cervical canal, being mainly sequelae of
      repeat Cesarean sections. Exceedingly rare are congenital VUFs. This is a
      systematic review of available world data aimed to characterize congenital VUFs
      and better understand the mechanism(s) of their formation. METHODS: The PubMed(r)
      database via MEDLINE(r) search engine was explored from its inception to March
      2018. Relevant studies were identified using selected Medical Subject Heading
      based terms. This was further supplemented by cross-referencing and
      handsearching. Retrieved literature was evaluated in line with the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, guidelines.
      RESULTS: A total of 6561 articles were identified of which 10 were analyzed.
      Three VUFs accompanied broader syndromes of congenital defects. A lack of patency
      at the level of the vagina was present in all assessed cases. Unilateral renal
      agenesis was confirmed in four of eight (50%) verified patients. Hence,
      unilateral kidney agenesis was related to a lesser degree (P = 0.0186) than
      vaginal atresia to VUF. The principal features of these fistulas were as follows:
      partial or complete vaginal atresia resulting in primary amenorrhea, menouria
      present since menarche, and urinary continence. CONCLUSIONS: This review provides
      the first systematic evidence that congenital VUFs are chiefly associated with
      concomitant vaginal atresia. The symptomatology of such VUFs is consistent with
      that of type I acquired fistulas.

PMID- 30106190
TI  - The cost of a catheter: An environmental perspective on single use clean
      intermittent catheterization.
AB  - METHODS: We estimated the prevalence of CIC use in the United States using a
      neurogenic population, consisting of persons with multiple sclerosis, spina
      bifida, and spinal cord injury. We measured catheter samples to obtain the amount
      of waste per catheter. RESULTS: At least 300 800 persons in the United States
      perform CIC for neurogenic bladder management. Assuming five catheterization
      events per day, the amount of waste generated by single-use CIC is between 26 500
      to 235 400 pounds or 22 600 to 564 000 liters per day, depending on catheter
      model. CONCLUSIONS: Single-use CIC may generate up to 85 million pounds or 206
      million liters of waste annually, equivalent to more than 26 000 cars or 80
      Olympic-sized swimming pools. Laid end-to-end, there is enough catheter length
      circumscribe the world more than 5.5 times. The most common materials used in
      catheter construction have little to no degradation once in a landfill. Given the
      unproven clinical benefit of single-use catheterization, the environmental impact
      and alternatives should be considered.

PMID- 30106191
TI  - Vascular measures of atherosclerosis in detrusor overactivity and controls.
AB  - AIM: The mechanisms leading to the development of detrusor overactivity (DO) are
      still relatively poorly understood, however, animal studies suggest that
      atherosclerosis and reduced blood flow to the bladder may be one etiological
      pathway. Thus, the aim of this study was to evaluate signs of atherosclerosis in
      a large cohort of women with detrusor overactivity, using two precise measures of
      atherosclerotic vascular impairment, Ankle Brachial Index (ABI), and Brachial
      ankle Pulse Wave Velocity (baPWV). METHODS: A prospective cohort study measuring
      ABI and baPWV of women with DO and controls was conducted. The ABI and baPWV were
      measured using an automated oscillometric blood pressure machine, to evaluate the
      degree of atherosclerosis in patients with DO and controls. Associations between
      ABI and baPWV and important confounding variables were assessed by a linear
      regression model. RESULTS: Ninety-eight women with DO, and 98 controls without
      any symptoms of DO were studied. Multivariate analysis showed an increase in left
      baPWV of approximately 96 cm/s units of velocity (95%CI 20.65-172.05, P = 0.01)
      is predicted significantly by the presence or absence of detrusor overactivity
      (as well by independent factors of age, diastolic blood pressure and body mass
      index). A similar effect was seen for right baPWV. CONCLUSIONS: On linear
      regression modeling, the presence of DO was a strong predictor for an increased
      PWV when controlling for age, BMI and diastolic blood pressure (DBP), thus
      supporting the hypothesis that atherosclerosis may contribute to the etiology of
      DO.

PMID- 30106192
TI  - DNA metabarcoding reveals changes in the contents of carnivorous plants along an
      elevation gradient.
AB  - Resource variation along abiotic gradients influences subsequent trophic
      interactions and these effects can be transmitted through entire food webs.
      Interactions along abiotic gradients can provide clues as to how organisms will
      face changing environmental conditions, such as future range shifts. However, it
      is challenging to find replicated systems to study these effects. Phytotelmata,
      such as those found in carnivorous plants, are isolated aquatic communities and
      thus form a good model for the study of replicated food webs. Due to the degraded
      nature of the prey, molecular techniques provide a useful tool to study these
      communities. We studied the pitcher plant Sarracenia purpurea L. in allochthonous
      populations along an elevational gradient in the Alps and Jura. We predicted that
      invertebrate richness in the contents of the pitcher plants would decrease with
      increasing elevation, reflecting harsher environmental conditions. Using
      metabarcoding of the COI gene, we sequenced the invertebrate contents of these
      pitcher plants. We assigned Molecular Operational Taxonomic Units at ordinal
      level as well as recovering species-level data. We found small but significant
      changes in community composition with elevation. These recovered sequences could
      belong to invertebrate prey, rotifer inquilines, pollinators and other animals
      possibly living inside the pitchers. However, we found no directional trend or
      site-based differences in MOTU richness with elevational gradient. Use of
      molecular techniques for dietary or contents analysis is a powerful way to
      examine numerous degraded samples, although factors such as DNA persistence and
      the relationship with species presence still have to be completely determined.

PMID- 30106193
TI  - Domperidone for insufficient lactation in England 2002-2015: A drug utilization
      study with interrupted time series analysis.
AB  - PURPOSE: Our aim was to describe trends in the prescription of domperidone for
      insufficient lactation in England, the characteristics of women prescribed it
      postpartum, and the impact of a 2014 European Medicines Agency (EMA)
      recommendation to restrict its use due to a potential increased risk of sudden
      cardiac death associated with its use. METHODS: We conducted a population-based
      cohort study with interrupted time series analysis using data from the Clinical
      Practice Research Datalink linked to Hospital Episode Statistics. We identified
      women with live births from 2002 to 2015, excluding those with nonlactation
      indications for domperidone (n = 247 349). We evaluated trends in the
      prescription rate of domperidone in the 6 months postpartum and differences in
      this rate before and after the EMA recommendation. RESULTS: Domperidone was
      prescribed among 1438 deliveries at a rate of 1.24 per 100 person-years. This
      rate increased from 0.56 to 2.1 per 100 person-years between 2002-2004 and 2011
      2013 (rate ratio: 3.8; 95% confidence interval [CI], 3.2-4.6). Prescribing
      decreased in level by 0.35 (95% CI, -0.86 to 0.16) per 100 person-years
      immediately following the recommendation with little change in trend (0.003; 95%
      CI, -0.059 to 0.065 per 100 person-years). Following the recommendation,
      prescription of doses >30 mg and coprescription of drugs with a risk of torsade
      de pointes decreased. No arrhythmic events were observed among domperidone users.
      CONCLUSIONS: Although we observed an important increase in prescribing during the
      study period, domperidone remains infrequently prescribed postpartum in England.
      While overall prescribing changed little, some prescribing practices became more
      restricted following the EMA's recommendation.

PMID- 30106194
TI  - Modafinil and the risk of cardiovascular events: Findings from three US claims
      databases.
AB  - PURPOSE: This study examined the potential risk of cardiovascular (CV) events
      associated with modafinil and the consistency of the risk estimates across
      databases. METHODS: A retrospective, inception cohort design of patients who
      initiated treatment with modafinil between 2006 and 2008 was used in three US
      health care claims databases. Modafinil users were matched with nonusers.
      Patients were further divided into two cohorts of obstructive sleep apnea (OSA)
      and non-OSA (NOSA) cohorts. Endpoints of interest, including myocardial
      infarction (MI), stroke, CV hospitalizations, and all-cause death, were assessed
      using incidence rates and Cox proportional hazard ratios (HRs), adjusted for
      potential confounding factors. RESULTS: The cohorts included a total of 175 524
      patients in MarketScan CM; 77 266-in IMS LifeLink; and 8174-in MarketScan
      Medicaid. No increased risk for MI in the OSA and NOSA cohorts was observed
      across all three databases. The risks of CV hospitalization in the OSA and NOSA
      cohorts were not different between the modafinil users and nonusers, except for
      IMS LifeLink database where the HR was lower than one in the modafinil users
      compared with the nonusers (HR, 0.69; 95% confidence interval [CI], 0.54 to
      0.87). For OSA patients with prior stroke, an adjusted HR of 1.96 (95% CI, 1.02
      to 3.76) was observed for stroke among modafinil users compared with nonusers.
      Among the NOSA, the HRs for all-cause death in the OSA were inconsistent across
      databases. CONCLUSIONS: Except for few CV outcomes, applying one common protocol
      generated consistent risk estimates of CV events following modafinil use across
      cohorts and databases.

PMID- 30106196
TI  - What triggers acute exacerbations of COPD? Why not ask the patient!

PMID- 30106195
TI  - Importance of main pancreatic duct dilatation in IPMN undergoing surveillance.
AB  - BACKGROUND: The association between risk of pancreatic cancer and a dilated main
      pancreatic duct (MPD) in intraductal papillary mucinous neoplasm (IPMN) is
      debated. The aim of this study was to assess the role of MPD size in predicting
      pancreatic cancer in resected IPMNs and those kept under surveillance. METHODS:
      All patients with IPMN referred to the Pancreas Institute, University of Verona
      Hospital Trust, from 2006 to 2016 were included. The primary endpoint was the
      occurrence of malignancy detected at surgery or during follow-up. RESULTS: The
      final cohort consisted of 1688 patients with a median follow-up of 60 months.
      Main pancreatic duct dilatation was associated with other features of malignancy
      in both the resected and surveillance groups. In patients who underwent
      resection, only a MPD of at least 10 mm was an independent predictor of
      malignancy. In patients kept under surveillance, MPD dilatation was not
      associated with malignancy. Fifteen of 71 patients (21 per cent) with malignancy
      in the resection cohort had a dilated MPD alone, whereas only one of 30 (3 per
      cent) under surveillance with MPD dilatation alone developed malignancy. Patients
      with a dilated MPD and other worrisome features had an increased 5-year
      cumulative incidence of malignancy compared with those with a non-dilated duct
      (11 versus 1.2 per cent; P < 0.001); however, the risk of malignancy was not
      significantly increased in patients with a dilated MPD alone (4 versus 1.2 per
      cent; P = 0.448). CONCLUSION: In patients under surveillance, a dilated MPD alone
      was not associated with an increased incidence of malignancy in IPMN.

PMID- 30106198
TI  - Electro-vectorcardiographic and electrophysiological aspects of Ebstein's
      anomaly.
AB  - Ebstein's anomaly is a congenital heart disease where the most important anatomic
      feature is the inferior displacement of the tricuspid valve leaflets.
      Vectorcardiographic features are mainly forgotten and electrocardiographic
      features may be unrecognized by cardiologists handling adult patients.

PMID- 30106197
TI  - Cognitive and neurobehavioral benefits of an enriched environment on young adult
      mice after chronic ethanol consumption during adolescence.
AB  - Binge drinking (BD) is a common pattern of ethanol (EtOH) consumption by
      adolescents. The brain effects of the acute EtOH exposure are well-studied;
      however, the long-lasting cognitive and neurobehavioral consequences of BD during
      adolescence are only beginning to be elucidated. Environmental enrichment (EE)
      has long been known for its benefits on the brain and may serve as a potential
      supportive therapy following EtOH exposure. In this study, we hypothesized that
      EE may have potential benefits on the cognitive deficits associated with BD EtOH
      consumption. Four-week-old C57BL/6J male mice were exposed to EtOH following an
      intermittent 4-day drinking-in-the-dark procedure for 4 weeks. Then they were
      exposed to EE during EtOH withdrawal for 2 weeks followed by a behavioral battery
      of tests including novel object recognition, novel location, object-in-place,
      rotarod, beam walking balance, tail suspension, light-dark box and open field
      that were run during early adulthood. Young adult mice exposed to EE
      significantly recovered recognition, spatial and associative memory as well as
      motor coordination skills and balance that were significantly impaired after
      adolescent EtOH drinking with respect to controls. No significant permanent
      anxiety or depressive-like behaviors were observed. Taken together, an EE exerts
      positive effects on the long-term negative cognitive deficits as a result of EtOH
      consumption during adolescence.

PMID- 30106199
TI  - The CXL12/CXCR4/CXCR7 axis in female reproductive tract disease: Review.
AB  - Initial studies on the chemokine stromal derived factor 1 (now referred to as
      CXCL12) were proposed to be enhanced in several diseases including those which
      affect the female reproductive tract. These include endometriosis, Asherman's
      syndrome, endometrial cancers, and ovarian cancers. Additionally, recent studies
      from our laboratory suggest that CXCL12 signaling is involved in leiomyomas
      (fibroids). These diseases present an inflammatory/hypoxic environment which
      further promotes pathology. At first, studies focused on signaling by CXCL12 via
      its well-known receptor, CXCR4. However, the discovery of CXCR7 as another
      receptor for CXCL12 with rather high binding affinity and recent reports about
      its involvement in endometrial disease and cancer progression has questioned the
      potential of "selective blockade"' of CXCR4 to treat these ailments. This review
      will focus on the signaling and effects of the potent chemokine CXCL12, and its
      long-known G protein-coupled receptor CXCR4, as well as the alternate receptor
      CXCR7 on the female reproductive tract and related diseases such as
      endometriosis, Asherman's syndrome, leiomyomas, endometrial cancer, and ovarian
      cancer. Although several other mechanisms are inherent to these diseases such as
      gene mutations, differential expression of miRNAs and epigenetics, for this
      review, we will focus on the CXCL12/CXCR4/CXCR7 axis as a novel target.

PMID- 30106200
TI  - Immunogenicity study of an expressed outer membrane protein U of Vibrio
      vulnificus in Japanese eel (Anguilla japonica).
AB  - AIMS: Vibrio vulnificus is a common bacterial pathogen causing haemorrhagic
      septicaemia in eel farming. This study investigates the immunogenicity of an
      outer membrane protein U (OmpU) of V. vulnificus and the feasibility of the
      protein as a new subunit vaccine against V. vulnificus. METHODS AND RESULTS:
      Partial gene sequence of the OmpU of V. vulnificus was cloned, and then the OmpU
      was expressed and purified. Three groups of Japanese eels (Anguilla japonica)
      were intraperitoneally (i.p) injected with bovine serum albumin (BSA group),
      formalin-killed whole cell of V. vulnificus (FKC group) or the expressed OmpU of
      V. vulnificus (OMP group). On 14, 21, 28 and 42 days postimmunization (dpi), the
      whole blood cells were collected to evaluate the stimulation index (SI) and
      bactericidal activity. The serum was obtained to assess the titres of specific
      antibody, lysozyme activity, complement activity and bactericidal activity. The
      lysozyme activities in the suspension of kidney, skin mucus and liver in eels
      were also ascertained. The results showed that the SI and the titres of anti-V.
      vulnificus antibody in the OMP group was significantly increased on 28 dpi;
      lysozyme activity in the kidney and skin mucus of OMP group on 42 and 14 dpi were
      both significantly higher than BSA group; eels in OMP group showed strong
      bactericidal capacity on 21 and 28 days; and the relative percent survival of OMP
      vs BSA group after challenged by V. vulnificus on 28 dpi was 80%. CONCLUSIONS:
      These results showed that the expressed OmpU of V. vulnificus could significantly
      improve the immune function of Japanese eel and the resistance of eels to the
      infection of V. vulnificus. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      offered an alternative preliminary strategy of making aquaculture vaccines
      against V. vulnificus for eel farming.

PMID- 30106201
TI  - Acute inferior myocardial infarction with right ventricular involvement and
      several clinical-electrocardiographic markers of poor prognosis.
AB  - Right ventricular involvement in inferior myocardial infarction is a marker of
      poor prognosis. We present a case of a 62-year-old man with very recent onset of
      acute chest pain and cardiac shock with the triad of elevated jugular venous
      pressure, distension of the jugular veins on inspiration, and clear lung fields.
      In addition, the admission electrocardiogram showed a slurring J wave or lambda
      like wave and conspicuous ST segment depression in several leads, predominantly
      in the lateral precordial (V4-V6), all clinical-electrocardiographic features of
      ominous prognosis.

PMID- 30106202
TI  - Observations on research with spores of Bacillales and Clostridiales species.
AB  - The purpose of this article is to highlight some areas of research with spores of
      bacteria of Firmicute species in which the methodology too commonly used is not
      optimal and generates misleading results. As a consequence, conclusions drawn
      from data obtained are often flawed or not appropriate. Topics covered in the
      article include the following: (i) the importance of using well-purified
      bacterial spores in studies on spore resistance, composition, killing,
      disinfection and germination; (ii) methods for obtaining good purification of
      spores of various species; (iii) appropriate experimental approaches to determine
      mechanisms of spore resistance and spore killing by a variety of agents, as well
      as known mechanisms of spore resistance and killing; (iv) common errors made in
      drawing conclusions about spore killing by various agents, including failure to
      neutralize chemical agents before plating for viable spore enumeration, and
      equating correlations between changes in spore properties accompanying spore
      killing with causation. It is hoped that a consideration of these topics will
      improve the quality of spore research going forward.

PMID- 30106203
TI  - Whom should I rely on for my future care? Patterns of care expectations and
      intergenerational correlates among ageing Chinese adults in Hong Kong.
AB  - This study examined ageing parents' care expectations across multiple care
      domains (financial and material, emotional, personal and informational) towards
      filial and formal sources and identified intergenerational correlates of care
      expectation patterns using a proposed care expectation model. Data of 780
      eligible ageing parents were drawn from a representative household survey of
      ageing adults (>=50 years) conducted in 2016-2017. Latent class analysis was used
      to examine the typological structure underlying ageing parents' care
      expectations. Four patterns of care expectations were discovered: mixed-maximal,
      filial-modest, formal-modest and neither-minimal. Multinomial logistic regression
      analysis was conducted to validate the newly proposed care expectation model. In
      addition to certain predisposing factors (participants' age, sex and education),
      parental enabling resources (economic status), health characteristics (physical,
      mental and functional health status), children-related enabling characteristics
      (number of sons and marital status of children), and intergenerational enabling
      circumstances (intergenerational relationships and caregiving to their own
      parents) were introduced into the model and found to be associated with ageing
      parents' care expectations. The findings can inform policy and programmes that
      effectively respond to ageing adults' diverse care expectations in Hong Kong and
      have implications for other Asian societies facing rapid population ageing and
      increasing care demands.

PMID- 30106204
TI  - Fetal sexual dimorphism in systemic soluble fms-like tyrosine kinase 1 among
      normotensive and preeclamptic women.
AB  - PROBLEM: A handful of studies report sexual dimorphism in the maternal angiogenic
      profile possibly influencing placental development and preeclampsia risk. This
      secondary analysis explored associations between fetal sex and soluble fms-like
      tyrosine kinase-1 (sFLT) and endoglin (9-35 weeks gestation) using data from a
      nested case-control study within the Danish National Birth Cohort. METHOD OF
      STUDY: A total of 448 preeclamptic women and 328 normotensive women had data on
      sFLT and endoglin. Preeclampsia was defined by blood pressure >=140/90 mm Hg and
      proteinuria (>=0.3g or 300 mg/24 h.). Generalized linear models adjusting for
      gestational age of blood draw, body mass index, maternal age, and smoking
      determined associations between fetal sex and log-transformed biomarkers.
      RESULTS: Male fetal sex is associated with 11% lower sFLT levels (beta = -0.11, P
      = 0.03) in preeclamptic women. There were no differences observed in normotensive
      women. We found no statistically significant differences in endoglin by fetal sex
      among groups. CONCLUSION: Our results are similar with other studies suggesting
      that women with female fetuses have increased sFLT levels. However, significant
      difference was only among women with preeclampsia. This study was exploratory and
      longitudinal investigations across pregnancy are required to understand the
      relationship between fetal sex and systemic maternal angiogenic biomarkers.

PMID- 30106205
TI  - Bifidobacterium animalis ssp. lactis Bb12 induces IL-10 through cell membrane
      associated components via TLR2 in swine.
AB  - AIM: To investigate the role of Toll-like receptor 2 (TLR2) in interleukin-10 (IL
      10) production induced by Bifidobacterium animalis ssp. lactis Bb12 (Bb12) in
      swine immune cells. METHODS AND RESULTS: Blood-monocytes and cells from
      mesenteric lymph nodes were obtained from pigs and cultured with live Bb12 for 4
      and 12 h. Transcript levels of IL-10 and TLR2 were analysed. Furthermore, TLR2
      was blocked to determine its participation in IL-10 production. TLR2 blockade was
      achieved with neutralizing antibodies, followed by stimulation with Bb12.
      Bifidobacteria induced IL-10 production in both swine monocytes and mesenteric
      cells. Monocytes with TLR2 blockade had a decrease in IL-10 transcripts, while
      mesenteric cells did not. Bacterial cell wall components were responsible for
      Bb12-induced IL-10 production since no IL-10 was detected in the culture
      supernatant. CONCLUSIONS: We demonstrated that IL-10 production is largely
      mediated through the recognition of Bb12 structures by TLR2, as bacterial
      metabolites in the culture supernatant failed to induce IL-10 expression.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The present study provides evidence for the
      potential use of Bb12 in the swine industry; these bacteria can also be used as
      additional method to treat intestinal inflammation and enhance intestinal health
      in pigs.

PMID- 30106206
TI  - Variation in activation time during bipolar vs extended bipolar left ventricular
      pacing.
AB  - BACKGROUND: Cardiac resynchronization therapy (CRT) is typically delivered via
      quadripolar leads that allow stimulation using either true bipolar pacing, where
      stimulation occurs between two electrodes (BP) on the quadripolar lead, or
      extended bipole (EBP) left ventricular (LV) pacing, with the quadripolar
      electrodes and right ventricular coil acting as the cathode and anode,
      respectively. True bipolar pacing is associated with reductions in mortality and
      it has been postulated that these differences are the result of enhanced
      electrical activation. MATERIALS AND METHODS: Patients undergoing a CRT underwent
      an electrocardiographic imaging study where electrical activation data were
      recorded while different LV pacing vectors were temporarily programmed. RESULTS:
      There were no differences in the total electrical activation times or dispersion
      of electrical activation between biventricular pacing with bipolar or
      corresponding EBP LV vector configurations (left ventricular total activation
      time [LVtat] BP 74.70 +/- 18.07 vs EBP 72.4 +/- 22.64; P = 0.45). When
      dichotomized according to etiology, no difference was observed in the activation
      time with either BP or EBP pacing (LVtat BP ischemic cardiomyopathy 72.2 +/- 17.4
      vs BP dilated cardiomyopathy 79.9 +/- 18.9; P = 0.38). CONCLUSIONS: Bipolar
      pacing alters the mechanical activation sequence of the LV and is associated with
      reductions in all-cause mortality. It has been postulated these benefits derive
      from improvements in electromechanical activation of the LV. Our study would
      suggest that true bipolar pacing does not necessarily result in more favorable
      activation of the LV or improved electrical resynchronization and other
      mechanisms should be explored.

PMID- 30106208
TI  - Three-way stopcock suture technique for hemostasis after ablation for atrial
      fibrillation.
AB  - BACKGROUND: Figure-of-eight sutures (F8S) have emerged as an alternative to the
      standard practice of manual compression to achieve venous hemostasis after
      catheter ablation for atrial fibrillation (AF). In lieu of a knot to secure the
      sutures in place, a three-way stopcock can be used, which can be loosened or
      tightened as needed to achieve hemostasis and is easier to remove. The safety and
      effectiveness of this technique, when compared to traditional F8S, are unknown.
      In this case series, we sought to describe this stopcock closure (SC) technique
      and compare procedural characteristics and outcomes to the traditional F8S.
      METHODS: Charts of consecutive patients who underwent AF radiofrequency at two
      centers were reviewed for the type of hemostasis (SC or F8S), demographics,
      periprocedural anticoagulation, groin complications, and procedural duration.
      RESULTS: A total of 100 patients were included (50 in the F8S group and 50 in the
      SC group). The two groups were similar in terms of mean age, gender, weight,
      renal function, oral anticoagulant use, and procedural heparin dosing. There was
      one groin bleeding complication in each group. The procedural time was shortened
      in the SC group (220 +/- 8 minutes vs 313 +/- 8 minutes), and there was more
      protamine use (25 vs 3 patients) owing to the differences in preferences among
      two operators. CONCLUSION: In this proof-of-concept study, a simple stopcock
      device provided comparable hemostasis to standard F8S after radiofrequency
      catheter ablation of AF.

PMID- 30106207
TI  - Pulmonary delivery of flecainide causes a rate-dependent predominant effect on
      atrial compared with ventricular depolarization duration revealed by intracardiac
      recordings in an intact porcine model.
AB  - BACKGROUND: Pulmonary delivery of flecainide results in the rapid conversion of
      atrial fibrillation (AF) to normal sinus rhythm in large-animal models and is
      safe and well-tolerated by normal human volunteers. OBJECTIVE: We investigated
      the effects of pulmonary delivery of flecainide on atrial and ventricular
      depolarization and repolarization duration. METHODS: Intratracheal instillation
      (1.5 mg/kg, rapid push) of flecainide or sterile water (placebo) was performed in
      12 closed-chest, anesthetized Yorkshire pigs with a catheter positioned at the
      bifurcation of the main bronchi. High-resolution electrograms obtained from
      catheters fluoroscopically positioned in the right atrium and left ventricle
      circumvented measurement errors due to the fusion of P and T waves in surface
      leads when rapid heart rates shortened the TP interval. Pacing was achieved using
      electrical stimuli delivered via right atrial catheter electrodes. RESULTS:
      During sinus rhythm (98 +/- 4.7 beats/min), intratracheal flecainide caused
      comparable (P = 0.56) increases in atrial depolarization (P a ) duration by 22%
      (39.8 +/- 3.2 to 48.7 +/- 3.3  milliseconds) and left ventricular (LV) QRS
      complex duration by 20% (47.9 +/- 1.6 to 57.3 +/- 1.8  milliseconds) at peak
      effect at 2 minutes post-dosing. During right atrial pacing at 180 beats/min, Pa
      duration increased by 55% (37.0 +/- 2.0 to 57.2 +/- 1.6  milliseconds; P <
      0.0001). The atrial response was greater (p = 0.001) than the 30% increase in LV
      QRS complex duration (46.6 +/- 1.7 to 60.6 +/- 2.5  milliseconds; P = 0.005). Pa
      duration and QRS complex duration were unchanged by placebo independent of pacing
      (P >= 0.4 for both). Atrial repolarization duration (PTa ; P = 0.46) and QTc
      interval (P = 0.49) remained unchanged. CONCLUSION: Intratracheal flecainide
      exerts a rate-dependent, predominant effect on atrial compared with ventricular
      depolarization duration. Pulmonary delivery of flecainide could facilitate AF
      conversion to sinus rhythm with reduced ventricular proarrhythmia risk.

PMID- 30106209
TI  - Alzheimer's disease and Type 2 Diabetes mellitus are distinct diseases with
      potential overlapping metabolic dysfunction upstream of observed cognitive
      decline.
AB  - Alzheimer's disease (AD) and type-2 diabetes mellitus (T2DM) are highly prevalent
      aging-related diseases associated with significant morbidity and mortality. Some
      findings in human and animal models have linked T2DM to AD-type dementia. Despite
      epidemiological associations between the T2DM and cognitive impairment, the
      interrelational mechanisms are unclear. The preponderance of evidence in
      longitudinal studies with autopsy confirmation have indicated that vascular
      mechanisms, rather than classic AD-type pathologies, underlie the cognitive
      decline often seen in self-reported T2DM. T2DM is associated with cardiovascular
      and cerebrovascular disease (CVD), and is associated with increased risk of
      infarcts and small vessel disease in the brain and other organs.
      Neuropathological examinations of post-mortem brains demonstrated evidence of
      cerebrovascular disease and little to no correlation between T2DM and beta
      amyloid deposits or neurofibrillary tangles. Nevertheless, the mechanisms
      upstream of early AD-specific pathology remain obscure. In this regard, there may
      indeed be overlap between the pathologic mechanisms of T2DM/"metabolic syndrome,"
      and AD. More specifically, cerebral insulin processing, glucose metabolism,
      mitochondrial function, and/or lipid metabolism could be altered in patients in
      early AD and directly influence symptomatology and/or neuropathology.

PMID- 30106210
TI  - Physical activity restriction for children and adolescents diagnosed with an
      inherited arrhythmia or cardiomyopathy and its impact on body mass index.
AB  - BACKGROUND: Historically, individuals diagnosed with an inherited arrhythmia or
      cardiomyopathy have been advised to avoid participating in competitive sports.
      Consequently, these individuals may be more susceptible to weight gain and
      obesity. METHODS: A retrospective longitudinal chart review was performed for a
      population of children with a genetic or clinical diagnosis of the long-QT
      syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic
      cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy. We recorded
      the physical activity recommendation, postdiagnosis sports participation, and
      body mass index (BMI) over time. RESULTS: A total of 109 charts were reviewed.
      Some level of physical activity restriction was documented for the majority of
      phenotype-positive children (80%) but was less common for phenotype-negative
      children (37%) (P < 0.001). Overall, 38% ( n = 41) of the study population were
      reportedly participating in a moderate or high dynamic sports following their
      diagnosis. Nonetheless, the BMI did not differ over time based on physical
      activity restriction or sports participation, and the proportion of overweight
      and obese children at follow-up was consistent with that seen in the Canadian
      pediatric population. CONCLUSION: Physical activity restriction was recommended
      for the majority of phenotype-positive children with an inherited arrhythmia or
      cardiomyopathy. However, many children continue to participate in competitive
      sports. Children prescribed physical activity restriction appear to face similar
      concerns relating to obesity as other Canadian children. This study highlights
      the need to further assess the effectiveness of physical activity recommendations
      and its impact on the cardiovascular health.

PMID- 30106211
TI  - Incessant supraventricular tachycardia: Why now?

PMID- 30106212
TI  - Prognostic significance of noncardiac syncope in the general population: A
      systematic review and meta-analysis.
AB  - INTRODUCTION: Cardiac syncope heralds significantly higher mortality compared
      with syncope due to noncardiac causes or unknown etiology, commonly considered a
      benign event. A few epidemiologic studies have examined the outcome of
      noncardiac/unexplained syncope comparing individuals with and without syncope,
      but with controversial results. We performed a systematic review and meta
      analysis to clarify whether history of noncardiac/unexplained syncope is
      associated with increased all-cause mortality in the general population. METHODS
      AND RESULTS: Our systematic review of the literature published between January 1,
      1966, and March 31, 2018 sought prospective, observational, cohort studies
      reporting summary-level outcome data about all-cause mortality in subjects with
      history of noncardiac/unexplained syncope compared with syncope-free
      participants. Adjusted hazard ratios were pooled through inverse variance random
      effect meta-analysis to compute the summary effect size. Meta-regression models
      were performed to explore the effect of age, cardiovascular risk factors, or
      other potential confounders on the measured effect size. We identified four
      studies including 287 382 individuals (51.6% men; age, 64 +/- 12 years): 38 843
      with history of noncardiac/unexplained syncope and 248 539 without history of
      syncope. The average follow-up was 4.4 years. History of noncardiac/unexplained
      syncope was associated with higher all-cause mortality (pooled adjusted hazard
      ratio = 1.13; 95% confidence interval, 1.05 to 1.23). Meta-regression analysis
      showed a stronger positive relationship proportional to aging and increasing
      prevalence of diabetes and hypertension. CONCLUSIONS: This study-level meta
      analysis showed that among older, diabetic and/or hypertensive individuals,
      history of noncardiac/unexplained syncope, even in the absence of an obvious
      cardiac etiology, is associated with higher all-cause mortality.

PMID- 30106213
TI  - Percutaneous cryoablation for papillary muscle ventricular arrhythmias after
      failed radiofrequency catheter ablation.
AB  - BACKGROUND: Catheter ablation of ventricular arrhythmias (VA) from the papillary
      muscles (PM) is challenging due to limited catheter stability and contact on the
      PMs with their anatomic complexity and mobility. OBJECTIVE: This study aimed to
      evaluate the effectiveness of cryoablation as an adjunctive therapy for PM VAs
      when radiofrequency (RF) ablation has failed. METHODS: We evaluated a
      retrospective series of patients who underwent cryoablation for PM VAs when RF
      ablation had failed. The decision to switch to cryoablation was at the operator's
      discretion when intracardiac echocardiography (ICE) suggested that cryoablation
      might be more effective in achieving catheter stability and energy delivery.
      RESULTS: Sixteen patients underwent cryoablation of PM VAs between 2014 and 2016
      after RF ablation was unsuccessful. VAs originated from the anterolateral left
      ventricle (LV) PM (six patients), posterolateral LV PM (six patients), and right
      ventricle PM (four patients). VAs were predominantly frequent premature
      ventricular complexes (PVCs); however, patients with sustained ventricular
      tachycardia and PVC-triggered VF were also represented. Fifteen of the 16
      patients were treated with cryoablation; in one patient, a procedural
      complication with retrograde aortic access precluded treatment. In all patients
      treated with cryoablation, contact and stability was confirmed with ICE to be
      superior to the RF catheter, and there was acute and long-term elimination of
      VAs. CONCLUSION: Cryoablation is a useful adjunctive therapy in ablation of PM
      VAs, providing excellent procedural outcomes even when RF ablation has failed.
      Cryoablation catheters are less maneuverable than RF ablation catheters and care
      is required to avoid complications.

PMID- 30106214
TI  - Cessation of pacing in super-responders of cardiac resynchronization therapy: A
      randomized controlled trial.
AB  - BACKGROUND: The consequence of cessation of biventricular pacing in super
      responders of cardiac resynchronization therapy (CRT) has not been fully
      investigated. METHODS: In this prospective, single-blinded clinical trial, 21
      super-responders were randomly assigned to the ceased pacing (CeP, 11 patients)
      group or the continued pacing (CoP, 10 patients) group. Patients randomized to
      the CeP group underwent cessation of biventricular pacing. New York Heart
      Association (NYHA) class, quality of life (QOL) assessed with Minnesota
      questionnaire, 6-minute walking distance (6MWD), left ventricular end systolic
      volume (LVESV), left ventricular end-diastolic volume (LVEDV), and left
      ventricular ejection fraction (LVEF) were compared between groups at 3- and 6
      month follow-up. RESULTS: No significant difference was observed between the CeP
      and CoP groups regarding NYHA class, QOL, 6MWD, LVESV, LVEDV, or LVEF after 3
      months (all P > 0.05). After 6 months, there existed no significant difference
      between the CeP and CoP groups with regard to NYHA class, QOL, 6MWD, LVESV, and
      LVEDV (all P > 0.05); however, LVEF was significantly lower in the CeP group than
      that of the CoP group (0.49 +/- 0.10 vs 0.60 +/- 0.11, P = 0.04), and LVEF was
      significantly reduced in the CeP group compared with the baseline value at
      randomization (0.49 +/- 0.10 vs 0.54 +/- 0.06, P = 0.04). CONCLUSION: LVEF was
      significantly reduced in super-responders of CRT 6 months after cessation of
      pacing. Super-responders to CRT should receive continued, long-term pacing to
      preserve recovered LV function.

PMID- 30106215
TI  - Smart Transformation of a Polyhedral Oligomeric Silsesquioxane Shell Controlled
      by Thiolate Silver(I) Nanocluster Core in Cluster@Clusters Dendrimers.
AB  - Using polyhedral oligomeric silsesquioxane (POSS) modified by a thiol group as a
      protected ligand, atom-precise multi-heteorocluster-based dendrimers Ag12 @POSS6
      (1 a and 1 b) were assembled. Through the reactive -SH groups, six POSS shell
      ligands stabilize the central 12-core silver(I) cluster by diverse Ag-S
      interactions. When such Ag12 @POSS6 complex was stimulated by different solvents
      (acetone or tetrahydrofuran), the core Ag12 silver(I) cluster underwent
      reversible structural transformation between flattened cubo-octahedral (in 1 a)
      and normal cubo-octahedral (in 1 b); concomitantly shell POSS clusters rearranged
      from pseudo-octahedral to quasi-octahedral. Furthermore, the film matrix modified
      by 1 a or 1 b showed different hydrophobicity.

PMID- 30106216
TI  - Abolition of T-wave alternans in a case of congenital long-QT syndrome with
      atrial pacing.

PMID- 30106217
TI  - Dietary specialization in mutualistic acacia-ants affects relative abundance but
      not identity of host-associated bacteria.
AB  - Acacia-ant mutualists in the genus Pseudomyrmex nest obligately in acacia plants
      and, as we show through stable isotope analysis, feed at a remarkably low trophic
      level. Insects with diets such as these sometimes depend on bacterial symbionts
      for nutritional enrichment. We, therefore, examine the bacterial communities
      associated with acacia-ants in order to determine whether they host bacterial
      partners likely to contribute to their nutrition. Despite large differences in
      trophic position, acacia-ants and related species with generalized diets do not
      host distinct bacterial taxa. However, we find that a small number of previously
      undescribed bacterial taxa do differ in relative abundance between acacia-ants
      and generalists, including several Acetobacteraceae and Nocardiaceae lineages
      related to common insect associates. Comparisons with an herbivorous generalist,
      a parasite that feeds on acacias and a mutualistic species with a generalized
      diet show that trophic level is likely responsible for these small differences in
      bacterial community structure. While we did not experimentally test for a
      nutritional benefit to hosts of these bacterial lineages, metagenomic analysis
      reveals a Bartonella relative with an intact nitrogen-recycling pathway
      widespread across Pseudomyrmex mutualists and generalists. This taxon may be
      contributing to nitrogen enrichment of its ant hosts through urease activity and,
      concordant with an obligately host-associated lifestyle, appears to be
      experiencing genomewide relaxed selection. The lack of distinctiveness in
      bacterial communities across trophic level in this group of ants shows a
      remarkable ability to adjust to varied diets, possibly with assistance from these
      diverse ant-specific bacterial lineages.

PMID- 30106218
TI  - MiR-520b restrains cell growth by targeting HDAC4 in lung cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) function as tumor promoting or tumor suppressing
      factors in many cancers. MiR-520b contributes to progression in head-neck and
      liver cancers, spinal osteosarcoma, and glioma; however, the association of miR
      520b with lung cancer progression remains unknown. In this investigation, we
      explore the effect of miR-520b targeting HDAC4 on lung cancer growth. METHODS:
      The regulation of miR-520b or its inhibitor on HDAC4 expression was analyzed
      using Western blot analysis. After treatment of miR-520b or its inhibitor, miR
      520b and HDAC4 levels were examined using quantitative real time-PCR. The
      modulation of miR-520b on HDAC4 was investigated by luciferase reporter gene
      assay. Cell proliferation evaluation was performed using colony formation and
      methyl-thiazolyl-tetrazolium assays. The correlation between miR-520b and HDAC4
      in human clinical samples was verified using Pearson's correlation coefficient.
      RESULTS: An obvious decrease in HDAC4 expression was observed in lung cancer A549
      cells treated with different doses of miR-520b. The miR-520b inhibitor enhanced
      HDAC4 expression in lung cancer cells. Bioinformatics predicted the targeting of
      miR-520b on HDAC4. MiR-520b directly targeted the 3' untranslated region of
      HDAC4. The introduction of miR-520b obviously inhibited cell proliferation in
      vitro. Anti-miR-520b was capable of accelerating lung cancer cell proliferation;
      however, HDAC4 knockdown destroyed anti-miR-520b-induced cell proliferation.
      Finally, a negative correlation between miR-520b and HDAC4 was observed in
      clinical human lung cancer samples. CONCLUSION: MiR-520b decreases HDAC4
      expression to control cell proliferation in lung cancer.

PMID- 30106219
TI  - Identification of novel immune-relevant drug target genes for Alzheimer's Disease
      by combining ontology inference with network analysis.
AB  - AIMS: Alzheimer's disease (AD) is one of the leading causes of death in elderly
      people. Its pathogenesis is greatly associated with the abnormality of immune
      system. However, only a few immune-relevant AD drug target genes have been
      discovered up to now, and it is speculated that there are still many potential
      drug target genes of AD (at least immune-relevant genes) to be discovered. Thus,
      this study was designed to identify novel AD drug target genes and explore their
      biological properties. METHODS: A combinatorial approach was adopted for the
      first time to discover AD drug targets by collectively considering ontology
      inference and network analysis. Moreover, a novel strategy limiting the distance
      of reasoning and in turn reducing noise interference was further proposed to
      improve inference performance. Potential AD drug target genes were discovered by
      integrating information of multiple popular databases (TTD, DrugBank, PharmGKB,
      AlzGene, and BioGRID). Then, the enrichment analyses of the identified drug
      targets genes based on nine well-known pathway-related databases were conducted
      to explore the function of the identified potential drug target genes. RESULTS:
      Eighteen potential drug target genes were finally identified, and 13 of them had
      been reported to be closely associated with AD. Enrichment analyses of these
      identified drug target genes, based on nine pathway-related databases, revealed
      that the enriched terms were primarily focus on immune-relevant biological
      processes. Four of those identified drug target genes are involved in the
      classical complement pathway and process of antigen presenting. CONCLUSION: The
      well-reproducible results showed the good performance of the combinatorial
      approach, and the remaining five new targets could be a good starting point for
      our understanding of the pathogenesis and drug discovery of AD. Moreover, this
      study supported validity of the combinatorial approach integrating ontology
      inference with network analysis in the discovery of novel drug target for
      neurological diseases.

PMID- 30106220
TI  - Live remote digital microscopy in peripheral blood smear evaluation:
      Intraobserver concordance and experience.
AB  - INTRODUCTION: Peripheral blood smear (PBS) review is a routine laboratory test
      which requires pathologist's interpretation when abnormal indices, atypical
      cells, or critical findings are identified. Real-time remote digital microscopy
      (DM) can potentially facilitate rapid review when an on-site pathologist is not
      available. Herein, we assess intraobserver concordance of PBS evaluation with
      light microscopy (LM) and DM using VisionTek M6 robotic DM and TeamViewer imaging
      software. METHODS: Thirty-seven de-identified PBS slides were evaluated by five
      reviewers. Slides were loaded on a VisionTek M6 robotic microscope at an off-site
      laboratory and evaluated remotely via TeamViewer software. Reviewers recorded
      interpretation, time required for interpretation (in minutes), imaging quality
      (score 0-3), and confidence of interpretation (score 0-3). Other relevant
      information associated with DM evaluation was also documented. Slides were
      subsequently evaluated using LM after washout interval. The intraobserver
      variation of results for impression, digital slide quality, minutes to
      interpretation, and confidence of interpretation was compared between DM and LM.
      RESULTS: The intraobserver concordance between LM and DM was 93%, with nine
      discordant interpretations among 135 evaluations under each review modality,
      respectively. Although reviewers spent more time under DM mode (5 min/slide) than
      LM mode (2.5 min/slide), the reviewers felt the DM provided sufficient image
      quality and the confidence levels of reviewers on slide interpretation were
      comparable between DM (2.6/3) and LM (2.8/3). CONCLUSION: There was a high level
      of intraobserver concordance and comparable interpretation confidence between DM
      and LM. DM can be a useful methodology for off-site pathologist's review of PBS.

PMID- 30106221
TI  - Insights into the GTP-dependent allosteric control of c-di-GMP hydrolysis from
      the crystal structure of PA0575 protein from Pseudomonas aeruginosa.
AB  - Bis-(3'-5')-cyclic diguanylic acid (c-di-GMP) belongs to the class of cyclic
      dinucleotides, key carriers of cellular information in prokaryotic and eukaryotic
      signal transduction pathways. In bacteria, the intracellular levels of c-di-GMP
      and their complex physiological outputs are dynamically regulated by
      environmental and internal stimuli, which control the antagonistic activities of
      diguanylate cyclases (DGCs) and c-di-GMP specific phosphodiesterases (PDEs).
      Allostery is one of the major modulators of the c-di-GMP-dependent response. Both
      the c-di-GMP molecule and the proteins interacting with this second messenger are
      characterized by an extraordinary structural plasticity, which has to be taken
      into account when defining and possibly predicting c-di-GMP-related processes.
      Here, we report a structure-function relationship study on the catalytic portion
      of the PA0575 protein from Pseudomonas aeruginosa, bearing both putative DGC and
      PDE domains. The kinetic and structural studies indicate that the GGDEF-EAL
      portion is a GTP-dependent PDE. Moreover, the crystal structure confirms the high
      degree of conformational flexibility of this module. We combined structural
      analysis and protein engineering studies to propose the possible molecular
      mechanism guiding the nucleotide-dependent allosteric control of catalysis; we
      propose that the role exerted by GTP via the GGDEF domain is to allow the two EAL
      domains to form a dimer, the species competent to enter PDE catalysis.

PMID- 30106222
TI  - Disease characteristics and treatment of patients with diabetes mellitus
      attending government health services in Indonesia, Peru, Romania and South
      Africa.
AB  - OBJECTIVE: To describe the characteristics and management of Diabetes mellitus
      (DM) patients from low- and middle-income countries (LMIC). METHODS: We
      systematically characterised consecutive DM patients attending public health
      services in urban settings in Indonesia, Peru, Romania and South Africa,
      collecting data on DM treatment history, complications, drug treatment, obesity,
      HbA1c and cardiovascular risk profile; and assessing treatment gaps against
      relevant national guidelines. RESULTS: Patients (median 59 years, 62.9% female)
      mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and
      central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was
      8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol;
      South Africa). Antidiabetes treatment included metformin (62.6%), insulin
      (37.8%), and other oral glucose-lowering drugs (34.8%). Disease complications
      included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease
      (16.5%) and proteinuria (14.7%). Many had an elevated cardiovascular risk with
      elevated blood pressure (36%), LDL (71.0%) and smoking (13%), but few were taking
      antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when
      indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives
      (39.5%) reached treatment targets according to national guidelines. There were
      large differences between countries in terms of disease profile and medication
      use. CONCLUSION: DM patients in government clinics in four LMIC with considerable
      growth of DM have insufficient glycaemic control, frequent macrovascular and
      other complications, and insufficient preventive measures for cardiovascular
      disease. These findings underline the need to identify treatment barriers and
      secure optimal DM care in such settings.

PMID- 30106223
TI  - 6th International Consultation on Incontinence. Recommendations of the
      International Scientific Committee: EVALUATION AND TREATMENT OF URINARY
      INCONTINENCE, PELVIC ORGAN PROLAPSE AND FAECAL INCONTINENCE.

PMID- 30106224
TI  - Systems biology approaches towards predictive microbial ecology.
AB  - Through complex interspecies interactions, microbial processes drive nutrient
      cycling and biogeochemistry. However, we still struggle to predict specifically
      which organisms, communities and biotic and abiotic processes are determining
      ecosystem function and how environmental changes will alter their roles and
      stability. While the tools to create such a predictive microbial ecology
      capability exist, cross-disciplinary integration of high-resolution field
      measurements, detailed laboratory studies and computation is essential. In this
      perspective, we emphasize the importance of pursuing a multiscale, systems
      approach to iteratively link ecological processes measured in the field to
      testable hypotheses that drive high-throughput laboratory experimentation.
      Mechanistic understanding of microbial processes gained in controlled lab systems
      will lead to the development of theory that can be tested back in the field.
      Using N2 O production as an example, we review the current status of field and
      laboratory research and layout a plausible path to the kind of integration that
      is needed to enable prediction of how N-cycling microbial communities will
      respond to environmental changes. We advocate for the development of realistic
      and predictive gene regulatory network models for environmental responses that
      extend from single-cell resolution to ecosystems, which is essential to
      understand how microbial communities involved in N2 O production and consumption
      will respond to future environmental conditions.

PMID- 30106225
TI  - Rehabilitation use in multiple sclerosis: Do illness representations matter?
AB  - OBJECTIVES: Multidisciplinary rehabilitation improves illness outcomes and is
      recommended in clinical guidelines for multiple sclerosis (MS). However, many
      people with MS do not make use of rehabilitation. We do not know much about the
      barriers to the use of rehabilitation in MS, but in other patient groups, illness
      representations have proven to be predictors of service utilization. Therefore,
      the aim of our study was to explore whether, in patients with MS, illness
      representations are associated with self-reports of rehabilitation use in the
      past and the intention to use rehabilitation in the future, beyond
      sociodemographic and illness-related factors. MATERIALS AND METHODS: Patients
      were recruited in a cross-sectional nationwide online survey in Germany.
      Hierarchical binary logistic regression analysis was used to analyze whether
      illness representations are associated with the use of rehabilitation in the past
      and the intention to use rehabilitation in the future, over and above socio
      demographic and illness-related variables. RESULTS: There were 590 patients, who
      had MS, participating in the study. Illness representations were correlated to
      both outcome variables beyond sociodemographic and illness-related factors: The
      probabilities of having the intention to use rehabilitation and of making using
      of rehabilitation were higher in patients who believed that their MS was
      controllable by treatment and perceived that their MS would have severe
      consequences. CONCLUSIONS: Our data suggest that addressing patients' illness
      representations may facilitate the intention to use and the use of multimodal
      rehabilitation, contributing to better illness outcomes.

PMID- 30106226
TI  - Long-read DNA metabarcoding of ribosomal RNA in the analysis of fungi from
      aquatic environments.
AB  - DNA metabarcoding is widely used to study prokaryotic and eukaryotic microbial
      diversity. Technological constraints limit most studies to marker lengths below
      600 base pairs (bp). Longer sequencing reads of several thousand bp are now
      possible with third-generation sequencing. Increased marker lengths provide
      greater taxonomic resolution and allow for phylogenetic methods of
      classification, but longer reads may be subject to higher rates of sequencing
      error and chimera formation. In addition, most bioinformatics tools for DNA
      metabarcoding were designed for short reads and are therefore unsuitable. Here,
      we used Pacific Biosciences circular consensus sequencing (CCS) to DNA
      metabarcode environmental samples using a ca. 4,500 bp marker that included most
      of the eukaryote SSU and LSU rRNA genes and the complete ITS region. We developed
      an analysis pipeline that reduced error rates to levels comparable to short-read
      platforms. Validation using a mock community indicated that our pipeline detected
      98% of chimeras de novo. We recovered 947 OTUs from water and sediment samples
      from a natural lake, 848 of which could be classified to phylum, 397 to genus and
      330 to species. By allowing for the simultaneous use of three databases (Unite,
      SILVA and RDP LSU), long-read DNA metabarcoding provided better taxonomic
      resolution than any single marker. We foresee the use of long reads enabling the
      cross-validation of reference sequences and the synthesis of ribosomal rRNA gene
      databases. The universal nature of the rRNA operon and our recovery of >100
      nonfungal OTUs indicate that long-read DNA metabarcoding holds promise for
      studies of eukaryotic diversity more broadly.

PMID- 30106227
TI  - Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via
      decreasing the ratio of sphingomyelin/ceramide.
AB  - Neutral sphingomyelinase 1 (NSMase1) mediates caspase-3 activation and apoptosis.
      However, the role of NSMase1, especially exosome-borne NSMase1 in hepatocellular
      carcinoma (HCC), remains unclear. We report that NSMase1, which converts
      sphingomyelin (SM) to ceramide, was significantly downregulated in HCC tissues.
      Low NSMase1 expression predicted poor long-term survival of HCC patients. NSMase1
      downregulation in HCC resulted in increased SM and reduced ceramide (Cer) that
      led to an increased SM/Cer ratio. Interestingly, NSMase1 and NSMase activity were
      also decreased in exosomes isolated from HCC tissues and cell lines. Furthermore,
      NSMase activity increased in exosomes isolated from the culture medium of L02
      cells transfected with pEGFP-C3-NSMase1 (NSMase1-Exo). NSMase1-Exo suppressed HCC
      cell growth and induced apoptosis via reduction of the SM/Cer ratio. Thus,
      NSMase1 in exosomes inhibits HCC growth by decreasing the SM/Cer ratio.

PMID- 30106229
TI  - Melatonin supplementation during prolonged in vitro maturation improves the
      quality and development of poor-quality porcine oocytes via anti-oxidative and
      anti-apoptotic effects.
AB  - Poor-quality oocytes (those with 1-2 layers of cumulus cells) typically possess
      low meiotic competence and development. Prolonging the duration of in vitro
      maturation (IVM; 52 hr) can enhance the maturation rate of poor-quality oocytes,
      but it does not improve subsequent embryonic development. This likely reflects
      the increased reactive oxygen species (ROS) production and apoptosis seen in
      these oocytes compared with the non-prolonged IVM (44 hr) group. Melatonin is a
      free radical scavenger, anti-oxidant and anti-apoptotic agent that reported to
      enhance the quality of embryos by inhibiting ROS generation and apoptosis.
      Therefore, we herein investigated whether melatonin combined with prolonged IVM
      (52 hr) could improve the quality and development of poor-quality oocytes. We
      supplemented IVM and/or in vitro culture (IVC) media with various concentrations
      (0, 10-7 , 10-6 , 10-5  M) of melatonin, and estimated parameters related to
      oocyte quality and development. The addition of melatonin (10-6  M) to a
      prolonged IVM system improved the oocyte quality and development compared with
      those of the melatonin-free poor-quality oocytes group, and that this was due to
      decreases in ROS generation, apoptosis, and DNA damage. When melatonin was added
      during both IVM (10-6  M) and IVC (10-6  M), we observed a cumulative positive
      influence on the embryonic development and quality; this treatment enhanced the
      expression level of Oct4 and decreased the levels of ROS, DNA damage, and
      apoptosis. Together, these findings suggest that the combination of melatonin
      plus prolonged IVM can improve the quality and development of poor-quality
      porcine oocytes via anti-oxidative and anti-apoptotic effects.

PMID- 30106228
TI  - What is the actual prevalence of migraine?
AB  - OBJECTIVES: Population prevalence studies of migraine report prevalence rates of
      between 2.6 and 21.7%, with an average of ~12%. However, migraine prevalence
      among neurologists is reported to be significantly higher, between 27.6% and
      48.6%. Increasing knowledge of the protean manifestations of migraine may explain
      this difference. Similarly, under-recognition of migraine in control groups may
      explain the lack of genetic and biomarker findings in this disorder. We therefore
      sought to determine the prevalence of migraine in an admixed group of individuals
      with varied knowledge of migraine symptomatology. METHODS: Attendees at the
      Australian and New Zealand Association of Neurologists Annual Scientific Meeting
      (ANZAN ASM) 2017 were surveyed anonymously. Those surveyed included three groups:
      neurologists, neurology trainees, and others including nonclinical researchers,
      members of lay organizations, and representatives of the pharmaceutical industry.
      RESULTS: In total, 313 of 606 attendees responded (51.7%). 65.9% of neurologist,
      57.4% of trainee, and 52.5% of others respondents had a personal history of
      migraine, with the difference between neurologists and others being statistically
      significant (p = .03). Migraine in migraineurs and nonmigraine headache in
      nonmigraineurs were nearly all self-diagnosed. Among neurologist migraineurs,
      51.2% experienced migraine with aura and 43% migraine without aura. CONCLUSIONS:
      Migraine prevalence is significantly higher in neurologists compared to non
      neurologists and at least 2-3 times higher than reported in population prevalence
      studies. This may be due to significant under-recognition of migraine in non
      neurologists. This under-recognition of migraine may significantly influence the
      search for genetic predictors and biomarkers of migraine.

PMID- 30106231
TI  - The effect of donor age on posttransplant mortality in a cohort of adult cardiac
      transplant recipients aged 18-45.
AB  - Hearts from older donors are increasingly utilized for transplantation due to
      unmet demand. Conflicting evidence exists regarding the prognosis of recipients
      of advanced age donor hearts, especially in young recipients. A retrospective
      analysis was performed on 11 433 patients aged 18 to 45 who received a cardiac
      transplant from 2000 to 2017. Overall, 10 279 patients received hearts from
      donors less than 45 and 1145 from donors greater than 45. Recipients of older
      donors were older (37 vs. 34 years, P < .01) and had higher rates of inotropic
      dependence (48% vs. 42%, P < .01). However, groups were similar in terms of
      comorbidities and dependence on mechanical circulatory support. Median survival
      for recipients of older donors was reduced by 2.6 years (12.6 vs. 15.2, P < .01).
      Multivariable analysis demonstrated donor age greater than 45 to be a predictor
      of mortality (HR 1.18 [1.05-1.33], P = .01). However, when restricting the
      analysis to patients who received a donor with a negative preprocurement
      angiogram, donor age only had a borderline association with mortality (HR 1.20
      [0.98-1.46], P = .06). Older donor hearts in young recipients are associated with
      decreased long-term survival, however this risk is reduced in donors without
      atherosclerosis. The long-term hazard of this practice should be carefully
      weighed against the risk of waitlist mortality.

PMID- 30106230
TI  - The behavioral study on the interactive aggravation between pruritus and
      depression.
AB  - BACKGROUND: The interactive aggravation of pruritus and depression is well-known,
      but an appropriate experimental model that could mimic this behavioral phenomenon
      is still lacking. Thus, a systematic animal behavioral investigation was carried
      out in this study. This will promote the research and treatment of pruritus and
      depression. METHODS: The 2,4-dinitrofluorobenzene (DNFB)-induced chronic itch
      model was established to measure the depression index by forced swimming test
      (FST), tail suspension test (TST), and splash test (ST). The chronic unpredicted
      mild stress (CUMS)-induced depression model was established to measure
      spontaneous itch and acute histamine or chloroquine-induced itch behaviors. A
      depression and itch combining model was also established to measure the
      scratching and depression behaviors. The motor function of DNFB mice was analyzed
      by the rotarod test. RESULTS: The scratching number, the immobility time in the
      FST and TST, and the grooming number in the ST test were all significantly
      increased in the chronic itch model. Mice receiving CUMS treatment showed
      significantly increased spontaneous scratching number, immobility time in the FST
      and TST tests, and grooming number in the ST. The combined model showed increased
      immobility time in FST and TST tests and increased grooming number in ST
      comparing to the depression model, and showed increased scratching number
      comparing to the chronic itch model. After histamine (His) or chloroquine (CQ)
      injection, the scratching numbers of CUMS mice were all significantly increased
      compared to those of His- and CQ-control, respectively. Anti-depression drug
      ketamine could significantly inhibit the depression-like behaviors of CUMS mice,
      and simultaneously stopped the promoting effect on His-induced acute itch.
      CONCLUSIONS: This study established an appropriate cross aggravation experimental
      mode and demonstrated that there is cross aggravation between pruritus and
      depression. The illumination of related mechanisms underlying this cross
      aggravation effect will provide theoretical basis for the prevention and
      treatment of depression and pruritus.

PMID- 30106232
TI  - C5aR1 regulates migration of suppressive myeloid cells required for costimulatory
      blockade-induced murine allograft survival.
AB  - Costimulatory blockade-induced murine cardiac allograft survival requires
      intragraft accumulation of CD11b+ Ly6Clo Ly6G- regulatory myeloid cells (Mregs)
      that expand regulatory T cells (Tregs) and suppress effector T cells (Teffs). We
      previously showed that C5a receptor (C5aR1) signaling on T cells activates Teffs
      and inhibits Tregs, but whether and/or how C5aR1 affects Mregs required for
      transplant survival is unknown. Although BALB/c hearts survived >60 days in anti
      CD154 (MR1)-treated or cytotoxic T-lymphocyte associated protein 4 (CTLA4)-Ig
      treated wild-type (WT) recipients, they were rejected at ~30 days in MR1-treated
      or CTLA4-Ig-treated recipients selectively deficient in C5aR1 restricted to
      myeloid cells (C5ar1fl/fl xLysM-Cre). This accelerated rejection was associated
      with ~2-fold more donor-reactive T cells and ~40% less expansion of donor
      reactive Tregs. Analysis of graft-infiltrating mononuclear cells on
      posttransplant day 6 revealed fewer Ly6Clo monocytes in C5ar1fl/fl xLysM-Cre
      recipients. Expression profiling of intragraft Ly6Clo monocytes showed that C5aR1
      deficiency downregulated genes related to migration/locomotion without changes in
      genes associated with suppressive function. Cotransfer of C5ar1fl/fl and
      C5ar1fl/fl xLysM-Cre myeloid cells into MR1-treated allograft recipients resulted
      in less accumulation of C5ar1- / - cells within the allografts, and in vitro
      assays confirmed that Ly6Chi myeloid cells migrate to C5a/C5aR1-initiated
      signals. Together, our results newly link myeloid cell-expressed C5aR1 to
      intragraft accumulation of myeloid cells required for prolongation of heart
      transplant survival induced by costimulatory blockade.

PMID- 30106234
TI  - A prospective observational study on the stress levels at the time of embryo
      transfer and pregnancy testing following in vitro fertilisation treatment: a
      comparison between women with different treatment outcomes.
AB  - OBJECTIVE: To ascertain whether stress biomarkers and psychological indices of
      stress may predict both conception and miscarriage rates in women undergoing in
      vitro fertilisation/intracytoplasmic sperm injection (IVF/ICSI). DESIGN:
      Prospective observational study. SETTING: A university-affiliated tertiary
      hospital. POPULATION: Infertile women who were undergoing fresh or frozen
      IVF/ICSI cycles. METHODS: Women were recruited to (1) complete validated
      psychological questionnaires (visual analogue scale of stress, state-trait
      anxiety inventory, perceived stress scale, fertility problem inventory, Beck
      depression inventory, and general health questionnaire), at the time of embryo
      transfer (ET) and pregnancy testing (PT), and (2) provide saliva samples for
      alpha-amylase (sAA) measurement before and after ET and at PT. MAIN OUTCOME
      MEASURES: Women were grouped according to subsequent reproductive outcome;
      scores/levels of all tests were then compared between groups at each time-point.
      RESULTS: In all, 197 women completed the study, of which 92 conceived and 28
      miscarried. The level of psychological stress, as measured by questionnaires, was
      highest at the time of PT, whereas the level of biological stress as measured by
      sAA level (IU/l) post-ET (1.8 * 105  +/- 1.5 * 105 ) was significantly (P <
      0.001) higher than pre-ET (1.2 * 105  +/- 1.0 * 105 ) and at PT (1.0 * 105  +/-
      1.1 * 105 ). However, there was no difference in psychological scoring and in sAA
      levels between women who did or did not conceive and who had miscarried or had an
      ongoing pregnancy. CONCLUSIONS: The level of sAA is highest following ET, whereas
      psychological stress is highest at PT. However, neither stress level appeared to
      be of prognostic value in predicting conception or miscarriage. TWEETABLE
      ABSTRACT: Stress level fluctuated at different time-points, but it did not
      predict conception or miscarriage.

PMID- 30106233
TI  - Facial candidiasis after maxillofacial trauma: A rare encounter.
AB  - Facial oedema after maxillofacial trauma is a common occurrence, but those that
      soon resolve only to appear again do invoke interest! A rare case is presented of
      a recurring facial swelling occurring after a maxillofacial injury that did not
      resolve subsequent to medication and repeated aspirations. Cytospin preparations
      of the aspirate stained with Giemsa revealed candidiasis. The patient's symptoms
      resolved soon with antifungal medications and he has been asymptomatic since.
      Such a scenario has never been reported in the literature and can pose a
      diagnostic dilemma. It gives insight into the unusual clinical presentation of
      facial candidiasis, the importance of thorough debridement of soft tissue wounds
      at primary care centres and the need to consider mycoses as a differential
      diagnosis for nonresolving soft tissue facial swellings after maxillofacial
      trauma.

PMID- 30106237
TI  - Cell signaling leads the way.

PMID- 30106236
TI  - Prediction of transplant outcome after 24-hour ex vivo lung perfusion using the
      Organ Care System in a porcine lung transplantation model.
AB  - Ex vivo lung perfusion (EVLP) has become routine practice in lung
      transplantation. Still, running periods exceeding 12 hours have not been
      undertaken clinically to date, and it remains unclear how the perfusion solution
      for extended running periods should be composed and which parameters may predict
      outcomes. Twenty-four porcine lungs underwent EVLP for 24 hours using the Organ
      Care System (OCS). Lungs were ventilated and perfused with STEEN's solution
      enriched with erythrocytes (n = 8), acellular STEEN's solution (n = 8), or low
      potassium dextran (LPD) solution enriched with erythrocytes (n = 8). After 24
      hours, the left lungs were transplanted into recipient pigs. After clamping of
      the contralateral lung, the recipients were observed for 6 hours. The most
      favorable outcome was observed in organs utilizing STEEN solution enriched with
      erythrocytes as perfusate, whereas the least favorable outcome was seen with LPD
      solution enriched with erythrocytes for perfusion. Animals surviving the
      observation period showed lower peak airway pressure (PAWP) and pulmonary
      vascular resistance (PVR) during OCS preservation. The results suggest that
      transplantation of lungs following 24 hours of EVLP is feasible but dependent on
      the composition of the perfusate. PAWP and PVR during EVLP are early and late
      predictors of transplant outcome, respectively.

PMID- 30106235
TI  - CXCL6-EGFR-induced Kupffer cells secrete TGF-beta1 promoting hepatic stellate
      cell activation via the SMAD2/BRD4/C-MYC/EZH2 pathway in liver fibrosis.
AB  - Liver fibrosis is the excessive accumulation of extracellular matrix proteins in
      response to the inflammatory response that accompanies tissue injury, which at an
      advanced stage can lead to cirrhosis and even liver failure. This study
      investigated the role of the CXC chemokine CXCL6 (GCP-2) in liver fibrosis. The
      expression of CXCL6 was found to be elevated in the serum and liver tissue of
      high stage liver fibrosis patients. Furthermore, treatment with CXCL6 (100 ng/mL)
      stimulated the phosphorylation of EGFR and the expression of TGF-beta in cultured
      Kupffer cells (KCs). Although treatment with CXCL6 directly did not activate the
      hepatic stellate cell (HSC) line, HSC-T6, HSCs cultured with media taken from KCs
      treated with CXCL6 or TGF-beta showed increased expression of alpha-SMA, a marker
      of HSC activation. CXCL6 was shown to function via the SMAD2/BRD4/C-MYC/EZH2
      pathway by enhancing the SMAD3-BRD4 interaction and promoting direct binding of
      BRD4 to the C-MYC promoter and CMY-C to the EZH2 promoter, thereby inducing
      profibrogenic gene expression in HSCs, leading to activation and
      transdifferentiation into fibrogenic myofibroblasts. These findings were
      confirmed in a mouse model of CCl4 -induced chronic liver injury and fibrosis in
      which the levels of CXCL6 and TGF-beta in serum and the expression of alpha-SMA,
      SMAD3, BRD4, C-MYC, and EZH2 in liver tissue were increased. Taken together, our
      results reveal that CXCL6 plays an important role in liver fibrosis through
      stimulating the release of TGF-beta by KCs and thereby activating HSCs.

PMID- 30106238
TI  - Synthesis of florisil materials modified with aliphatic or aromatic groups and
      the application for pipette-tip solid-phase extraction of rutin in orange peel.
AB  - After being coupled, florisil was modified with four kinds of aliphatic or
      aromatic groups and were applied to the determination of rutin in orange peel
      sample by a pipette-tip solid-phase extraction method. The materials were
      characterized by scanning electron microscopy, Fourier transform infrared
      spectroscopy, thermogravimetric analysis and specific surface area by Brunauer
      Emmett Teller N2 adsorption desorption analysis. Florisil and five modified
      materials were tested by static adsorption, and the result showed that the
      material with 4-bromoanisole had the best adsorption amount for rutin. Under
      optimum conditions: 4 mg of the adsorbent, 1 mL of MeOH as washing solvent, and 1
      mL of MeOH/acetic acid (85:15, v/v) as elution solvent were used in the pipette
      tip solid-phase extraction procedure. The calibration graphs of rutin in MeOH
      were linear over 1-200 MUg/mL, and the limits of detection and quantification
      were 0.13 and 0.42 MUg/mL. The method recoveries of rutin were in the range of
      83.66-98.40% with associated intra- and interday relative standard deviations in
      the range of 1.31-3.50% and 1.04-2.03%, respectively. The material with 4
      bromoaniline showed satisfactory results (recovery: 98.40%). It was potential for
      the rapid purification of rutin in orange peel sample combined with pipette-tip
      solid-phase extraction.

PMID- 30106240
TI  - Catalytic Enantioselective [10+4] Cycloadditions.
AB  - The first peri- and stereoselective [10+4] cycloaddition between catalytically
      generated amino isobenzofulvenes and electron-deficient dienes is described. The
      highly stereoselective catalytic [10+4] cycloaddition exhibits a broad scope with
      high yields, reflecting a robust higher-order cycloaddition. Experimental and
      computational investigations support a kinetic distribution of intermediate
      rotamers dictating the enantioselectivity, which relies heavily on additive
      effects.

PMID- 30106239
TI  - Sleep disturbances and depression severity in patients with Parkinson's disease.
AB  - OBJECTIVES: Parkinson's disease (PD) is a multisystem movement disorder
      associated with sleep disturbance and depression. Sleep disturbances and
      depression severity share a bidirectional association. This association may be
      greater in individuals who are more vulnerable to the deleterious consequences of
      sleep disturbance and depression severity. We investigated whether the
      association between sleep disturbances and depression severity is greater in
      patients with PD than in matched controls (MC). MATERIALS AND METHODS: The study
      sample (N = 98) included 50 patients with idiopathic PD and 48 age-, race-, sex-,
      and education-matched controls. Sleep disturbances were assessed using self
      reported total sleep time (TST) on the Pittsburgh Sleep Quality Index, the sleep
      item on the Beck Depression Inventory, 2nd ed. (BDI-II), and the Insomnia
      Severity Index total score. Depression severity was assessed using the BDI-II
      total score, excluding the sleep item. Spearman's correlations, chi-squared
      tests, and multiple regression were used to assess associations between sleep
      disturbances and depression severity in PD and MC. Fisher's Z transformation was
      used to test whether the association between sleep disturbances and depression
      severity was stronger in patients with PD. RESULTS: Shorter TST, sleeping less
      than usual, and insomnia severity were associated with depression severity in the
      total sample, rs(94) = -0.35, p = .001; rs(71) = 0.51, p < .001; rs(78) = -0.47,
      p < .001; rs(98) = 0.46, p < .001, respectively. The association between shorter
      TST and depression severity was greater in patients with PD than it was in MC, p
      < .05. CONCLUSION: Short TST may be an important marker, predictor, or
      consequence of depression severity in patients with Parkinson's disease.

PMID- 30106241
TI  - Pattern of mortality after menopausal hormone therapy: long-term follow up in a
      population-based cohort.
AB  - OBJECTIVE: To investigate long-term pattern of mortality in menopausal women
      according to different modalities of hormone therapy. DESIGN: Population-based
      prospective cohort study. SETTING: Denmark 1993-2013. POPULATION: A total of 29
      243 women aged 50-64 years at entry into the Diet, Cancer and Health Cohort,
      enrolled 1993-97 and followed through 31 December 2013. METHODS: Cox'
      proportional hazards models for increasingly longer periods of follow-up time
      were used to estimate mortality pattern according to baseline hormone use
      adjusted for relevant potential confounders. MAIN OUTCOME(S): All-cause and cause
      specific mortality. Outcome information was obtained from the Danish Register of
      Causes of Death (linkage 99.6%). RESULTS: A total of 4098 women died during a
      median follow up of 17.6 years. After adjustment for relevant lifestyle risk
      factors, hormone use had no impact on all-cause mortality, regardless of
      modality. Among baseline users, lower cardiovascluar disease mortality was only
      evident after 5 years [hazard ratio (HR) 0.54; 95% CI 0.32-0.92], but dissipated
      with additional follow up. Conversely, lower colorectal cancer mortality (HR
      0.64; 95% CI 0.46-0.89) and higher breast cancer mortality (HR 1.34; 95% CI 1.05
      1.72) only became evident after 15 years of follow up. There were no significant
      associations for mortality from other types of cancer or from stroke.
      CONCLUSIONS: In this long-term follow-up study, taking hormones during menopause
      was not associated with overall mortality among middle-aged women. Investigating
      cause-specific mortality revealed significant, albeit weak, differential
      associations according to both causes of death and over time, underlining the
      importance of carefully considering individual risks and duration of treatment
      when making decisions on hormone therapy. TWEETABLE ABSTRACT: Long-term follow-up
      study confirms no association between menopausal hormone therapy and overall
      mortality.

PMID- 30106242
TI  - Taxon cycle predictions supported by model-based inference in Indo-Pacific trap
      jaw ants (Hymenoptera: Formicidae: Odontomachus).
AB  - Nonequilibrium dynamics and non-neutral processes, such as trait-dependent
      dispersal, are often missing from quantitative island biogeography models despite
      their potential explanatory value. One of the most influential nonequilibrium
      models is the taxon cycle, but it has been difficult to test its validity as a
      general biogeographical framework. Here, we test predictions of the taxon cycle
      model using six expected phylogenetic patterns and a time-calibrated phylogeny of
      Indo-Pacific Odontomachus (Hymenoptera: Formicidae: Ponerinae), one of the ant
      genera that E.O. Wilson used when first proposing the hypothesis. We used model
      based inference and a newly developed trait-dependent dispersal model to jointly
      estimate ancestral biogeography, ecology (habitat preferences for forest
      interiors, vs. "marginal" habitats, such as savannahs, shorelines, disturbed
      areas) and the linkage between ecology and dispersal rates. We found strong
      evidence that habitat shifts from forest interior to open and disturbed habitats
      increased macroevolutionary dispersal rate. In addition, lineages occupying open
      and disturbed habitats can give rise to both island endemics re-occupying only
      forest interiors and taxa that re-expand geographical ranges. The phylogenetic
      predictions outlined in this study can be used in future work to evaluate the
      relative weights of neutral (e.g., geographical distance and area) and non
      neutral (e.g., trait-dependent dispersal) processes in historical biogeography
      and community ecology.

PMID- 30106243
TI  - Blastomatoid pulmonary carcinosarcoma: A rare case report and review of the
      literature.
AB  - A 65-year-old never-smoking woman presented to a local hospital, because an
      abnormal shadow was detected at the right lower lung field by annual chest X-ray.
      Computed tomography (CT) revealed a 5-cm tumor in segment 6 of her right lung and
      an enlarged subcarinal lymph node, suggesting metastasis. The lung tumor was
      diagnosed as adenocarcinoma by a CT-guided percutaneous needle biopsy. She was
      referred to our hospital and underwent right lower lobectomy with lymph node
      dissection (ND2a-2). A histopathological examination of the tumor showed a
      biphasic proliferation made of carcinomatous and sarcomatous components. The
      carcinomatous component consisted of glandular structures of atypical cells that
      possessed chromatin-rich nuclear and clear cytoplasm, confirming high-grade fetal
      adenocarcinoma. The sarcomatous component consisted of immature spindle cells
      that differentiated into chondrosarcoma. Immunohistochemically, the glandular
      structures expressed membranous beta-catenin, and the ultimate diagnosis was
      blastomatoid variant of pulmonary carcinosarcoma. She received four courses of
      cisplatin plus vinorelbine as adjuvant chemotherapy and remained alive with
      neither recurrence nor distant metastasis at two and a half years after the
      operation. We experienced a rare case of blastomatoid pulmonary carcinoasarcoma.

PMID- 30106244
TI  - Acute noncontrast T1-weighted magnetic resonance imaging predicts chronic
      radiofrequency ablation lesions.
AB  - BACKGROUND: Magnetic resonance imaging (MRI) has been used to visualize
      radiofrequency (RF) ablation lesions but the relationship between volumes that
      enhance in acute MRI and the chronic lesion size is unknown. OBJECTIVES: The main
      goal was to use noncontrast (native) T1-weighted (T1w) MRI and late gadolinium
      enhancement (LGE)-MRI to visualize lesions acutely and chronically and correlate
      the acute area of enhancement with chronic lesion size in histology. MATERIALS
      AND METHODS: In a canine (n = 9) model RF ablation lesions were created in both
      ventricles. Native T1w MRI and LGE-MRI were acquired acutely after the ablation
      procedure. After 8 weeks, another set of RF ablations was performed, and the MRI
      study was repeated. Volume and depth of enhancement in native T1w MRI and LGE-MRI
      acquired after the initial ablation procedure were correlated with chronic lesion
      volume and depth in histology. RESULTS: Thirty-three lesions were analyzed.
      Native T1w MRI visualized the acute lesions but not the chronic lesions. LGE-MRI
      showed both acute and chronic lesions. Acute native T1w MRI volume (average of
      102.1 +/- 48.5 mm3 ) and depth (4.9 +/- 1.2 mm) correlated well with chronic
      histological volume (105.9 +/- 51.8 mm3 ) and depth (4.8 +/- 1.3 mm) with R2 of
      0.881 (P < 0.001) and 0.874 (P < 0.001), respectively. Acute LGE-MRI had a
      significantly higher volume of enhancement of 499.7 +/- 214.4 mm3 (P < 0.001) and
      depth of 7.5 +/- 1.8 mm ( P < 0.001) when compared with chronic histological
      lesion volume and depth. CONCLUSIONS: Native T1w MRI acquired acutely after RF
      ablation is a good predictor of chronic lesion size. Acute LGE-MRI significantly
      overestimates the chronic lesion size.

PMID- 30106245
TI  - Genetic influences on prefrontal activation during a verbal fluency task in
      children: A twin study using near-infrared spectroscopy.
AB  - OBJECTIVE: The genetic and environmental influences on prefrontal function in
      childhood are underinvestigated due to the difficulty of measuring prefrontal
      function in young subjects, for which near-infrared spectroscopy (NIRS) is a
      suitable functional neuroimaging technique that facilitates the easy and
      noninvasive measurement of blood oxygenation in the superficial cerebral
      cortices. METHOD: Using a two-channel NIRS arrangement, we measured changes in
      bilateral prefrontal blood oxygenation during a category version of the verbal
      fluency task (VFT) in 27 monozygotic twin pairs and 12 same-sex dizygotic twin
      pairs ages 5-17 years. We also assessed the participant's full-scale intelligence
      quotient (FIQ) and retrieved parental socioeconomic status (SES). Classical
      structured equation modeling was used to estimate the heritability. RESULTS: The
      heritability of VFT-related brain activation was estimated to be 44% and 37% in
      the right and left prefrontal regions, respectively. We also identified a
      significant genetic contribution (74%) to FIQ, but did not to VFT task
      performance. Parental SES was not correlated with FIQ, task performance, or task
      related prefrontal activation. CONCLUSIONS: This finding provides further
      evidence that variance in prefrontal function has a genetic component since
      childhood and highlights brain function, as measured by NIRS, as a promising
      candidate for endophenotyping neurodevelopmental disorders.

PMID- 30106246
TI  - Altered somatosensory neurovascular response in patients with Becker muscular
      dystrophy.
AB  - INTRODUCTION: Patients with dystrophinopathies show low levels of neuronal nitric
      oxide synthase (nNOS), due to reduced or absent dystrophin expression, as nNOS is
      attached to the dystrophin-associated protein complex. Deficient nNOS function
      leads to functional ischemia during muscle activity. Dystrophin-like proteins
      with nNOS attached have also been identified in the brain. This suggests that a
      mechanism of cerebral functional ischemia with attenuation of normal activation
      related vascular response may cause changes in brain function. METHODS: The aim
      of this study was to investigate whether the brain response of patients with
      Becker muscular dystrophy (BMD) is dysfunctional compared to that of healthy
      controls. To investigate a potential change in brain activation response in
      patients with BMD, median nerve somatosensory evoked stimulation, with
      stimulation durations of 2, 4, and 10 s, was performed while recording
      electroencephalography and blood oxygen level-dependent (BOLD) functional
      magnetic resonance imaging. RESULTS: Results in 14 male patients with BMD (36.2
      +/- 9.9 years) were compared with those of 10 healthy controls (34.4 +/- 10.9
      years). Compared to controls, the patients with BMD showed sustained cortical
      electrical activity and a significant smaller BOLD activation in contralateral
      primary somatosensory cortex and bilaterally in secondary somatosensory cortex.
      In addition, significant activation differences were found after long duration
      (10 s) stimuli in thalamus. CONCLUSION: An altered neurovascular response in
      patients with BMD may increase our understanding of neurovascular coupling and
      the pathogenesis related to dystrophinopathy and nNOS.

PMID- 30106247
TI  - miRNA-regulated transcription associated with mouse strains predisposed to
      hypnotic effects of ethanol.
AB  - INTRODUCTION: Studying innate sensitivity to ethanol can be an important first
      step toward understanding alcohol use disorders. In brain, we investigated
      transcripts, with evidence of miRNA modulation related to a predisposition to the
      hypnotic effect of ethanol, as measured by loss of righting reflex (LORR).
      METHODS: Expression of miRNAs (12 samples) and expression of mRNAs (353 samples)
      in brain were independently analyzed for an association with LORR in mice from
      the LXS recombinant inbred panel gathered across several small studies. These
      results were then integrated via a meta-analysis of miRNA-mRNA target pairs
      identified in miRNA-target interaction databases. RESULTS: We found 112
      significant miRNA-mRNA pairs where a large majority of miRNAs and mRNAs were
      highly interconnected. Most pairs indicated a pattern of increased levels of
      miRNAs and reduced levels of mRNAs being associated with more alcohol-sensitive
      strains. For example, CaMKIIn1 was targeted by multiple miRNAs associated with
      LORR. CAMK2N1 is an inhibitor of CAMK2, which among other functions,
      phosphorylates, or binds to GABAA and NMDA receptors. CONCLUSIONS: Our results
      suggest a novel role of miRNA-mediated regulation of an inhibitor of CAMK2 and
      its downstream targets including the GABAA and NMDA receptors, which have been
      previously implicated to have a role in ethanol-induced sedation and sensitivity.

PMID- 30106248
TI  - D-cycloserine-augmented one-session treatment of specific phobias in children and
      adolescents.
AB  - BACKGROUND: D-Cycloserine has potential to enhance exposure therapy outcomes. The
      current study presents a preliminary randomized, placebo-controlled double-blind
      pilot trial of DCS-augmented one-session treatment (OST) for youth (7-14 years)
      with specific phobia. A secondary aim of this pilot study was to explore the
      effects of youth age and within-session fear reduction as potential moderators of
      DCS outcomes in order to generate hypotheses for a larger trial. It was
      hypothesized that DCS would be associated with greater improvements than placebo,
      that children (7-10 years) would have greater benefits than adolescents (11-14
      years), and that DCS effects would be stronger for participants with the greater
      within-session fear reduction during the OST. METHODS: Thirty-five children and
      adolescents were randomized to either OST combined with DCS (n = 17), or OST
      combined with placebo (PBO; n = 18) and assessed at 1 week, 1 month, and 3 month
      following treatment. RESULTS: There were no significant pre- to post-treatment or
      follow-up benefits of DCS relative to placebo. Secondary analyses of age
      indicated that relative to PBO, DCS was associated with greater improvements for
      children (but not adolescents) on measures of severity at 1-month follow-up.
      Children in the DCS condition also showed significantly greater improvement to 1
      month on global functioning relative to other groups. Conversely, adolescents had
      significant post-treatment benefits in the PBO condition on symptom severity
      measures relative to DCS, and adolescents in the DCS condition had significantly
      poorer functioning at 3 months relative to all other groups. Finally, there was a
      trend for within-session fear reduction to be associated with moderating effects
      of DCS, whereby greater reduction in fear was associated with greater functioning
      at one-month follow-up for children who received DCS, relative to PBO.
      LIMITATIONS: The study sample was small and therefore conclusions are tentative
      and require replication. CONCLUSIONS: Age and within-session fear reduction may
      be important moderators of DCS-augmented one-session exposure therapy, which
      requires testing in a fully powered randomized controlled trial.

PMID- 30106249
TI  - Risk of knee oa with obesity, sarcopenic obesity and sarcopenia.
AB  - OBJECTIVE: Obesity, defined by anthropometric measures, is a well-known risk
      factor for knee osteoarthritis (OA) but there is a relative paucity of data
      regarding the association of body composition (fat and muscle mass) on knee OA
      risk. We examined the longitudinal association of body composition categories
      based on fat and muscle mass with incident knee OA risk. METHODS: We included
      participants from The Multicenter Osteoarthritis (MOST) Study, a longitudinal
      cohort of individuals with or at risk for knee OA. Based on body composition
      (i.e. fat and muscle mass) from whole body Dual Energy X-ray (DXA), subjects were
      categorized as: 1) obese; 2) sarcopenic obese; 3) sarcopenic; and 4) non
      sarcopenic non-obese. We examined the relation of baseline body composition
      categories to the risk of incident radiographic OA at 60 months using binomial
      regression with robust variance estimation, adjusting for potential confounders.
      RESULTS: Among 1653 subjects without radiographic knee OA at baseline,
      significant increased risk of incident radiographic knee OA was found among obese
      (women RR 2.29, 95% CI 1.64-3.20; men RR 1.73, 95% CI 1.08-2.78) and sarcopenic
      obese women (RR 1.91, 95% CI 1.17-3.11), but not men (RR 1.74, 95% CI 0.68-4.46)
      subjects. Sarcopenia was not associated with knee OA risk (women RR 0.96, 95% CI
      0.62-1.49; men RR 0.66; 95% CI 0.34-1.30). CONCLUSIONS: In this large
      longitudinal cohort, we found body composition based obesity and sarcopenic
      obesity but not sarcopenia, to be associated with knee OA risk. Weight loss
      strategies for knee OA should focus on obesity and sarcopenic obesity. This
      article is protected by copyright. All rights reserved.

PMID- 30106250
TI  - Electrical stimulation-based nerve location prediction for cranial nerve VII
      localization in acoustic neuroma surgery.
AB  - INTRODUCTION: Cranial nerve (CN) VII localization is a critical step during
      acoustic neuroma surgery because the nerve is generally hidden due to the tumor
      mass. The patient can suffer from Bell's palsy if the nerve is accidentally
      damaged during tumor removal. Surgeons localize CN VII by exploring the target
      area with a stimulus probe. Compound muscle action potentials (CMAPs) are
      elicited when the probe locates the nerve. However, false positives and false
      negatives are possible due to unpredictable tissue impedance in the operative
      area. Moreover, a single CMAP amplitude is not correlated with probe-to-nerve
      distance. OBJECTIVES: This paper presents a new modality for nerve localization.
      The probe-to-nerve distance is predicted by the proposed nerve location
      prediction model. METHODS: Input features are extracted from CMAP responses,
      tissue impedance, and stimulus current. The tissue impedance is calculated from
      the estimated resistance and capacitance of the tissue equivalent circuit. In
      this study, experiments were conducted in animals. A frog's sciatic nerve and
      gastrocnemius were used to represent CN VII and facial muscle in humans,
      respectively. Gelatin (2.8%) was used as a mock material to mimic an acoustic
      neuroma. The %NaCl applied to the mock material was used to emulate
      uncontrollable impedance of tissue in the operative area. RESULTS: The 10-fold
      cross-validation results revealed an average prediction accuracy of 86.71% and an
      average predicted error of 0.76 mm compared with the measurement data.
      CONCLUSION: The proposed nerve location prediction model could predict the probe
      to-nerve distance across various impedances of the mock material.

PMID- 30106251
TI  - Cntn6 deficiency impairs allocentric navigation in mice.
AB  - INTRODUCTION: CNTN6 is an immunoglobulin domain-containing cell adhesion molecule
      that belongs to the contactin family. It is involved in the development of the
      nervous system. We aim to determine the effect of Cntn6 deficiency on the
      allocentric navigation in mice. METHODS: We recorded the travel distance and
      escape time of wild-type and Cntn6 mutant male and female mice in the Morris
      water maze task according to the protocol. RESULTS: There was hardly any Cntn6
      expression in the hippocampus of postnatal day 0 (P0) mice, while obvious Cntn6
      expression was present in the hippocampal CA1 region of the P7 mice. During the
      acquisition period of Morris water maze task (Day 1 to 4), Cntn6-/- male mice
      failed to shorten the escape time to reach platform on the third day, while the
      travel distance to platform was not significantly different. There was no
      significant difference in both escape time and travel distance to the platform
      among all female subjects. In the probe trial test (Day 5), spatial memory of the
      female mutant mice was mildly affected, while Cntn6-/- male mice were normal. In
      the spatial relearning test (Day 7 to 10), Cntn6-/- male mice showed no
      difference in escape time to the platform compared to the wild-type male mice,
      while Cntn6 deficient female mice required shorter escape time to travel to the
      platform on day 7, day 8, and day 10. CONCLUSIONS: Cntn6 is expressed in the
      developing hippocampus in mice. Cntn6 deficiency affects spatial learning and
      memory, indicating that Cntn6 plays a role in the development of hippocampus and
      affects allocentric navigation of the animals.

PMID- 30106252
TI  - Enhanced switching and familial susceptibility for psychosis.
AB  - INTRODUCTION: Working Memory and Task-Switching are essential components of
      cognitive control, which underlies many symptoms evident across multiple
      neuropsychiatric disorders, including psychotic and mood disorders. Vulnerability
      to these disorders has a substantial genetic component, suggesting that
      clinically unaffected first-degree relatives may carry some vulnerability-related
      traits. Converging evidence from animal and human studies demonstrates that
      dopamine transmission, striatal and frontal brain regions, and attention and
      switching behaviors are essential components of a multilevel circuit involved in
      salience, and disruptions in that circuit may lead to features of psychosis. Yet,
      it is possible that unaffected relatives may also possess characteristics that
      protect against development of illness. We hypothesized that reduced switch cost
      in a cued task-switching task, may be a behavioral expression of this
      "resilience" phenotype that will be observable in unaffected relatives. METHODS:
      We tested a large community sample (n = 536) via the web, to assess different
      subcomponents of cognitive control, including task-switching and working memory,
      as well as risk-taking, among individuals who report having an affected relative
      with a psychotic or mood disorder. RESULTS: Healthy individuals with suspected
      genetic risk due to a self-reported familial history of a psychotic disorder
      demonstrated better task-switching performance compared to healthy people without
      a psychiatrically ill relative and those with a relative with a mood disorder.
      This result was specific to illness status and task domain, in that individuals
      with a personal history of depression or anxiety did not show improved task
      switching performance, and this improvement was selective to task-switching and
      not seen in other putative cognitive control domains (working memory or risk
      taking). CONCLUSIONS: Although this study has limitations and independent
      replication is needed, these preliminary findings suggest a potential avenue for
      understanding susceptibility to these disorders by highlighting possible
      protective as well as vulnerability-related aspects of risk phenotypes.

PMID- 30106254
TI  - Nest-building activity as a reproducible and long-term stroke deficit test in a
      mouse model of stroke.
AB  - INTRODUCTION: Neuroprotective therapeutics achieved from animal studies have not
      been able to translate into clinical stroke therapies. A major reason may be that
      the functional tests and outcomes between animal stroke studies and clinical
      trials are significantly different. Ultimately, functional recovery is most
      important for stroke patients, but it remains challenging to identify animal
      functional tests that reflect human stroke deficits. This study aimed to explore
      whether the nest-building activity can be used as a functional test of mouse
      stroke deficit. METHODS: Forty-one C57B6 male mice were randomly assigned into a
      sham-operated control group and 20-, 40- and 60-min middle cerebral artery
      occlusion (MCAO) groups. Mice were perfusion-fixed at 21 days following sham
      surgery or MCAO. Infarct volumes were assessed under the light microscopy. The
      nest-building activity was characterized and quantitatively evaluated. RESULTS:
      The results show that only a small portion of striatum was damaged after 20-min
      MCAO. The brain damage areas were expanded from striatum to the neocortex and
      hippocampus proportionally after 40-min and 60-min MCAO, respectively.
      Consistently, relative to that of the sham-operated mice, the nest-building
      activity was insignificantly altered after 20-min MCAO, but dramatically and
      significantly reduced proportionally following 40-min and 60-min MCAO,
      respectively. The nest-building deficit was a long-lasting event and could be
      seen for as long as 14-21 days of recovery, the longest endpoint of this study.
      CONCLUSIONS: The results suggest that the nest-building activity may be a novel,
      objective, easy to use, highly sensitive, and long-lasting test that may reflect
      the multifaceted sensorimotor and cognitive deficits after stroke in humans. Our
      findings may provide a novel multifaceted test for bridging the gap between
      animal stroke studies and clinical trials.

PMID- 30106253
TI  - The effect of a single dose of escitalopram on sensorimotor networks.
AB  - INTRODUCTION: Serving as a pilot study of poststroke pharmacotherapy, the present
      investigation was intended to establish the effect of a single dose of
      escitalopram on motor task performance in normal volunteers. METHODS: Ten healthy
      volunteers of median age 63 years including four females performed a well-studied
      tactile manipulation task in two fMRI sessions using a double-blind cross-over
      design. The sessions began approximately three hours after ingestion of 20 mg
      escitalopram or placebo presented in pseudorandom order. The fMRI image sequences
      were submitted to principal component analysis (PCA). RESULTS: Based on volume
      correlations of task-related principal components with the mean component images
      derived in our previous study, we established the reproducibility of two networks
      of sensorimotor activity proposed there. The network reflecting motor control
      (cerebral pattern I) appeared invariably in placebo and verum conditions. In
      contrast, the other network, attributed to diminished motor control due to
      distracting mental processing (cerebral pattern II), emerged less regularly and
      exhibited more variability. Second-level PCAs of both conditions confirmed the
      findings of the initial analysis. Specifically, it validated the dominant and
      invariable expression of cerebral pattern I after application of a single dose of
      escitalopram. Dynamic causal modeling confirmed enhanced motor output as a result
      of a significantly increased connectivity between primary motor cortex and dorsal
      premotor cortex. CONCLUSION: This pilot study suggests the promise of stimulation
      by a specific serotonin reuptake inhibitor in regard to recovery and preservation
      of motor control after stroke.

PMID- 30106255
TI  - Association between the rs7583431 single nucleotide polymorphism close to the
      activating transcription factor 2 gene and the analgesic effect of fentanyl in
      the cold pain test.
AB  - BACKGROUND: Activating transcription factor 2 (ATF2) is a member of the leucine
      zipper family of DNA binding proteins and is widely distributed in tissues.
      Several recent studies have demonstrated that this protein is involved in
      mechanisms that are related to pain and inflammation. However, unclear is whether
      polymorphisms of the ATF2 gene, which encodes the human ATF2 protein, influence
      pain or analgesic sensitivity. This study examined associations between the
      analgesic effect of fentanyl in the cold pressor-induced pain test and
      polymorphisms in the ATF2 gene in 355 Japanese subjects. RESULTS: In this study,
      33 single nucleotide polymorphisms (SNPs) were selected, and a total of 2 linkage
      disequilibrium blocks with 6 Tag SNPs (rs1153702, rs7583431, rs2302663,
      rs3845744, rs268214, and rs1982235) were observed in the region within and around
      the ATF2 gene. We further analyzed associations between these Tag SNPs and
      clinical data. Even after multiple testing with Bonferroni adjustments, an
      increase in the analgesic effect of fentanyl in the cold pressor-induced pain
      test was significantly associated with a greater number of the A allele of the
      rs7583431 SNP (linear regression, P = .001). CONCLUSIONS: The present findings
      may contribute to adequate pain relief in individual patients. Although more
      research on the genetic factors that influence opioid sensitivity is needed,
      analgesic requirements may be predicted by analyzing ATF2SNPs, together with
      other polymorphisms of genes that are reportedly associated with opioid
      sensitivity, such as CREB1, OPRM1, and GIRK2.

PMID- 30106256
TI  - Early manifestation of depressive-like behavior in transgenic mice that express
      dementia with Lewy body-linked mutant beta-synuclein.
AB  - AIM: We previously generated transgenic (Tg) mice that expressed P123H beta
      synuclein (betaS), a dementia with Lewy body-linked mutant betaS. Notably, these
      mice recapitulated neurodegenerative features of Lewy body disease, reflected by
      motor dysfunction, greater protein aggregation, and memory impairment. Since
      recent studies suggested that non-motor symptoms, such as depression, might be
      manifested in the prodromal stage of Lewy body disease, the main objective of the
      present study was to investigate the early expression of behavior in P123H betaS
      Tg mice. METHODS: Nest building, locomotor activity, and depressive-like behavior
      were assessed using 6- to 10-month-old male and female P123H betaS Tg and
      wildtype mice. KEY RESULTS: P123H betaS Tg mice exhibited hyperlocomotor activity
      in a novel environment, a decrease in mobility time in the tail suspension test,
      and impairments in nest building. CONCLUSIONS: Importantly, these non-motor
      behaviors were manifested before the onset of motor dysfunction, suggesting that
      P123H betaS Tg mice could be a valid model for investigating the early phase of
      Lewy body disease.

PMID- 30106257
TI  - Comparative analysis of palmitoylation sites of serotonin (5-HT) receptors in
      vertebrates.
AB  - BACKGROUND: In the vertebrate central nervous system as well as in the periphery,
      serotonin, also known as 5-hydroxytriptamine (5-HT), function as a
      neurotransmitter, a hormone or a mitogen. 5-HT receptors are composed of 7 family
      5-HT1-7 receptors, comprising of 14 structurally and pharmacologically distinct 5
      HT receptor subtypes. Previous experimental studies showed that mouse 5-HT1A , 5
      HT4 and 5-HT7 receptors are regulated by post-translational protein
      palmitoylation, the reversible attachment of the lipid palmitate to intracellular
      cysteine residues. Here, we further focused on conservation of these putative
      palmitoylation sites found in vertebrate 5-HT receptor orthologs. METHODS AND
      RESULTS: Analysis of sequence databases provides evidence to suggest that
      palmitoylation sites of these 5-HT receptors have been extremely conserved in the
      vertebrate lineages from jawless fishes to human, in spite of the divergence of 5
      HT1A , 5-HT4 or 5-HT7 receptors full-length amino acid sequences during molecular
      evolution. CONCLUSION: Our findings mean that dynamic regulation of 5-HT
      receptors made possible by reversible post-translational protein palmitoylation
      may be critical for refined functions of the vertebrate serotonergic systems.

PMID- 30106258
TI  - Association between rs2275913 single-nucleotide polymorphism of the interleukin
      17A gene and perioperative analgesic use in cosmetic orthognathic surgery.
AB  - AIM: Interleukin-17A (IL-17A) plays an essential role in tissue inflammation by
      inducing proinflammatory cytokine and chemokine production and is related to
      innate immune reactions. IL-17A also contributes to neuroinflammation,
      neuropathic pain, and mechanical hypersensitivity after peripheral nerve injury
      in rodents. To clarify the contribution of IL-17A to pain-related phenotypes in
      humans, we investigated the association between pain-related phenotypes and the
      rs2275913 single-nucleotide polymorphism (SNP) of the IL-17A gene, which has been
      reported to be associated with rheumatoid arthritis, ulcerative colitis, and some
      cancers. METHODS: The present study used a correlational design to examine the
      impact of the rs2275913 SNP on postoperative pain-related phenotypes in a group
      of patients who underwent cosmetic orthognathic surgery. RESULTS: Carriers of the
      AA genotype had higher opioid requirements during and after surgery than carriers
      of the AG and GG genotypes (P = .009). Linear regression analysis indicated that
      opioid requirements linearly increased as the copy number of the A allele of the
      SNP increased (P = .008). CONCLUSIONS: Opioid requirements during and after
      surgery are enhanced in carriers of the AA genotype of the rs2275913 SNP of the
      IL-17A gene, possibly through an enhancement of IL-17A function that induces
      inflammation that is related to the inflammatory pain stimulus.

PMID- 30106259
TI  - Possible effects of electroconvulsive therapy on refractory psychosis in primary
      progressive multiple sclerosis: A case report.
AB  - INTRODUCTION: Patients with multiple sclerosis commonly show some degree of
      psychiatric symptoms. Primary progressive multiple sclerosis is a part of the
      spectrum of multiple sclerosis phenotypes with progressive accumulation of
      disability from disease onset and active course. Psychiatric symptoms are
      commonly shown in multiple sclerosis, and up to 10% of patients with multiple
      sclerosis have the primary progressive form. Thus, patients with primary
      progressive multiple sclerosis may also elicit psychiatric symptoms. However,
      little information is available on psychiatric symptoms, especially on psychosis,
      in primary progressive multiple sclerosis. CASE: Here, we report on a 42-year-old
      woman with primary progressive multiple sclerosis whose psychosis did not respond
      to antipsychotics and was partially ameliorated by electroconvulsive therapy. She
      suffered from auditory hallucination, anxiety, depersonalization, and suicidal
      ideation. Initially, several antipsychotic agents were tried, but not effective.
      Given this, she underwent 12 sessions of electroconvulsive therapy. CONCLUSION:
      Our observation suggests the possible utility of electroconvulsive therapy in the
      treatment of psychosis in primary progressive multiple sclerosis.

PMID- 30106260
TI  - N-methyl-d-aspartate receptor dysfunction in the prefrontal cortex of stroke
      prone spontaneously hypertensive rat/Ezo as a rat model of attention
      deficit/hyperactivity disorder.
AB  - AIM: We previously reported that stroke-prone spontaneously hypertensive rat/Ezo
      (SHRSP/Ezo) has high validity as an attention deficit/hyperactivity disorder
      (AD/HD) animal model, based on its behavioral phenotypes, such as inattention,
      hyperactivity, and impulsivity. Fronto-cortical dysfunction is implicated in the
      pathogenesis of AD/HD. In this study, we investigated prefrontal cortex (PFC)
      function in SHRSP/Ezo rats by electrophysiological methods and radioreceptor
      assay. METHODS: We recorded excitatory postsynaptic potential in layer V
      pyramidal neurons in the PFC by intracellular recording method to assess synaptic
      plasticity in the form of long-term potentiation (LTP). We also performed N
      methyl-d-aspartate acid (NMDA) receptor binding assay in the PFC and hippocampus
      using radiolabeled NMDA receptor antagonist [3 H]MK-801. RESULTS: Theta-burst
      stimulation induced LTP in the PFC of genetic control, WKY/Ezo, whereas failed to
      induce LTP in that of SHRSP/Ezo. The Kd value of [3 H]MK-801 binding for NMDA
      receptors in the PFC of SHRSP/Ezo was higher than in the WKY/Ezo. Neither the
      Bmax nor Kd of [3 H]MK-801 binding in the SHRSP/Ezo hippocampus was significantly
      different to WKY/Ezo. CONCLUSION: These results suggest that the AD/HD animal
      model SHRSP/Ezo has NMDA receptor dysfunction in the PFC.

PMID- 30106261
TI  - Comprehensive behavioral analysis of tryptophan 2,3-dioxygenase (Tdo2) knockout
      mice.
AB  - AIMS: Tryptophan 2,3-dioxygenase (TDO2) is an initial rate-limiting enzyme of the
      kynurenine (Kyn) pathway in tryptophan (Trp) metabolism. The Trp-degrading
      enzymes, TDO2 and indoleamine 2,3-dioxygenase, are activated by stress and/or
      inflammation. Dysregulation of Trp metabolism, which causes shifts in the balance
      between Kyn and serotonin (5-HT) pathways, is associated with psychiatric and
      neurological disorders. In genetic studies, single-nucleotide polymorphisms in
      the TDO2 gene were shown to be involved in psychiatric disorders, such as
      schizophrenia and depression. It has been reported that targeted deletion of the
      Tdo2 gene in mice resulted in reduced anxiety-like behavior, enhanced exploratory
      activity and cognitive performance, and increased levels of Trp and 5-HT in the
      hippocampus and midbrain. However, the effect of Tdo2 gene deletion on behavioral
      phenotypes has not yet been investigated extensively. MATERIALS & METHODS: We
      conducted tests to further examine the behavioral effects of knockout (KO) of
      Tdo2 in mice. RESULTS: Deletion of Tdo2 resulted in seemingly lower anxiety-like
      behavior, higher locomotor activity, and abnormal gait pattern in mice, though
      none of them reached study-wide statistical significance. Tdo2 deficiency had no
      significant effects on other behaviors, such as prepulse inhibition, and
      depression-like and social behaviors. DISCUSSION AND CONCLUSION: He lack of clear
      phenotypes in Tdo2KO mice in this study might be due to the absence of stress and
      inflammatory conditions, which could induce expression of Tdo2 mRNA. Further
      studies are necessary to elucidate the roles of Tdo2 in behavioral phenotypes
      related to psychiatric disorders.

PMID- 30106262
TI  - Bidirectional brain-gut interactions: Involvement of noradrenergic transmission
      within the ventral part of the bed nucleus of the stria terminalis.
AB  - INTRODUCTION: Although the important roles of bidirectional interactions between
      the brain and gut in stress and emotional responses have long been recognized,
      the underlying neuronal mechanisms remain unclear. The bed nucleus of the stria
      terminalis (BNST) is a limbic structure involved in stress responses and negative
      affective states, such as anxiety and depression. We have previously demonstrated
      that noradrenergic transmission within the ventral part of the BNST (vBNST) plays
      a crucial role in anxiety-like behaviors and pain-induced aversion. OBJECTIVES:
      This study aimed to examine the involvement of noradrenergic transmission via
      beta-adrenoceptors within the vBNST in bidirectional brain-gut interactions.
      METHODS: We measured the gastric distention (GD)-induced noradrenaline release
      within the vBNST of freely moving rats using an in vivo microdialysis technique.
      Gastric emptying and intestinal transit were examined following intra-vBNST
      injections of isoproterenol, a beta-adrenoceptor agonist, in the absence or
      presence of the coadministration of timolol, a beta-adrenoceptor antagonist.
      RESULTS: Gastric distention at a higher pressure (45 mm Hg) but not at a lower
      pressure (25 mm Hg) resulted in a significant increase in extracellular
      noradrenaline levels within the vBNST. Intra-vBNST injections of isoproterenol
      (30 nmol/side) induced significant reductions in gastric emptying and small
      intestinal transit, both of which were reversed by the coadministration of
      timolol (30 nmol/side). CONCLUSION: Noradrenergic transmission via beta
      adrenoceptors within the vBNST was involved in bidirectional brain-gut
      interactions. These findings suggest that gastric dysfunction may induce negative
      affective states via the enhanced release of noradrenaline within the vBNST
      which, in turn, may cause gastrointestinal impairments.

PMID- 30106263
TI  - Cerebellar activation during a motor task in conversion disorder with motor
      paralysis: A case report and fMRI study.
AB  - BACKGROUND: Motor conversion disorders are characterized by movement symptoms
      without a neurological cause. A psychogenic etiology is presumed for these
      disorders, but little is known about their underlying neural mechanisms.
      Functional magnetic resonance imaging (fMRI) has been utilized to understand the
      mechanisms associated with unexplained motor symptoms. Here, we used fMRI to
      investigate the cerebral response to motor stimulation in a patient with
      conversion disorder with motor paralysis to determine the underlying neural
      mechanisms of this disorder. METHODS: Brain activation induced by movements of
      the bilateral ankle joints (repeated plantar flexion and dorsiflexion) was
      recorded using fMRI in a patient with conversion disorder with unexplained motor
      paralysis. We acquired 2 types of imaging data: (i) data obtained while motor
      paralysis remained present and (ii) data obtained after motor paralysis had
      completely improved. We used a within-subject fMRI block design to compare the
      patient's brain activities during the motor task and at rest. RESULTS: Cerebral
      motor areas were significantly activated during the motor task relative to at
      rest, both when motor paralysis remained present and when paralysis had improved
      (FWE-corrected P < .05), although there was greater activation in motor areas
      when motor paralysis had improved than when motor paralysis remained. Notably,
      activation in the cerebellum posterior lobe during the motor task when motor
      paralysis remained (FWE-corrected P < .05) disappeared after motor paralysis had
      completely improved. CONCLUSIONS: The cerebellum is a region that is closely
      associated with voluntary motion. We suggest that complementary abnormal function
      in the cerebellum might be associated with the neural basis of conversion
      disorder with motor paralysis.

PMID- 30106264
TI  - A pharmacogenetics approach to pain management.
AB  - INTRODUCTION: Opioid analgesics are widely used as effective analgesics for the
      treatment of moderate-to-severe pain. However, the analgesic efficacy of opioids
      is well known to vary widely among individuals, and effective pain treatment is
      hampered by vast individual differences. Although these differences in opioid
      requirements have been attributed to various factors, genetic factors are
      becoming increasingly relevant to the development of genome science. AIM: This
      review covers the association between opioid analgesic requirements and
      particularly gene polymorphisms. FUTURE PERSPECTIVES: Personalized pain treatment
      has begun using prediction formulas based on associated gene polymorphisms.
      Improvements in personalized pain treatment are expected as scientific knowledge
      further expands in the future.

PMID- 30106265
TI  - Behavioral effects of long-term oral administration of aluminum ammonium sulfate
      in male and female C57BL/6J mice.
AB  - BACKGROUND: Aluminum (Al) is considered to be a neurotoxic metal, and excessive
      exposure to Al has been reported to be a potential risk factor for
      neurodegenerative diseases. Al ammonium sulfate is one of the Al compounds that
      is widely used as a food additive. However, the effects of the oral
      administration of Al ammonium sulfate on physical development and behavior remain
      to be examined. METHODS: In this study, we investigated the effects of the
      administration of Al ammonium sulfate 12-water dissolved in drinking water (0.075
      mg/mL) beginning in adolescence on various types of behavior in adult female
      C57BL/6J mice through a battery of behavioral tests (low-dose experiment;
      Experiment 1). We further examined the behavioral effects of the oral
      administration of a higher dose of the Al compound in drinking water (1 mg/mL)
      beginning in the prenatal period on behavior in adult male and female mice (high
      dose experiment; Experiment 2). RESULTS: In the low-dose experiment, in which
      females' oral intake of Al was estimated to be 0.97 mg Al/kg/d as adults, Al
      treated females exhibited an increase in total arm entries in the elevated plus
      maze test, an initial decrease and subsequent increase in immobility in the
      forced swim test, and reduced freezing in the fear conditioning test
      approximately 1 month after the conditioning session compared with vehicle
      treated females (uncorrected P < .05). However, the behavioral differences did
      not reach a statistically significant level after correction for multiple
      testing. In the high-dose experiment, in which animals' oral intakes were
      estimated to be about ten times higher than those in the low-dose experiment,
      behavioral differences found in the low-dose experiment were not observed in high
      dose Al-treated mice, suggesting that the results of the low-dose experiment
      might be false positives. Additionally, although high-dose Al-treated females
      exhibited increased social contacts with unfamiliar conspecifics and impaired
      reference memory performance, and high-dose Al-treated mice exhibited decreases
      in prepulse inhibition and in correct responses in the working memory task
      (uncorrected P < .05), the differences in any of the behavioral measures did not
      reach the significance level after correction for multiple testing. CONCLUSION:
      Our results show that long-term oral exposure to Al ammonium sulfate at the doses
      used in this study may have the potential to induce some behavioral changes in
      C57BL/6J mice. However, the behavioral effects of Al were small and statistically
      weak, as indicated by the fact that the results failed to reach the study-wide
      significance level. Thus, further study will be needed to replicate the results
      and reevaluate the behavioral outcomes of oral intake of Al ammonium sulfate.

PMID- 30106266
TI  - A randomized controlled study of the effect of ifenprodil on alcohol use in
      patients with alcohol dependence.
AB  - AIM: This prospective, randomized, controlled, rater-blinded study investigated
      the effect of G protein-activated inwardly rectifying potassium (GIRK) channel
      inhibitor ifenprodil on alcohol use in patients with alcohol dependence. METHODS:
      The participants were 68 outpatients with alcohol dependence who were assigned to
      an ifenprodil group (administered 60 mg ifenprodil per day for 3 months) or
      control group (administered 600 mg ascorbic acid and calcium pantothenate per day
      for 3 months). The participants completed a questionnaire that included the
      frequency of alcohol drinking and presence of heavy drinking before the study
      period (time 1) and 3 months after the start of the study period (time 2). The
      alcohol use score was calculated using these two items. RESULTS: Valid data were
      obtained from 46 participants (25 in the ifenprodil group and 21 in the control
      group). The alcohol use score at time 2 in the ifenprodil group was significantly
      lower than that in the control group after adjusting for the score at time 1 and
      some covariates. The intention-to-treat analysis of multiply imputed datasets
      indicated similar results. Group differences in the frequency of alcohol drinking
      were significant in the multiply imputed datasets but not in 46 participants. The
      ifenprodil group had a significantly lower rate of heavy drinking at time 2 than
      the control group. CONCLUSIONS: This study found an inhibitory effect of
      ifenprodil on alcohol use in patients with alcohol dependence. The results
      support the hypothesis that GIRK channel inhibitors ameliorate alcohol
      dependence. TRIAL REGISTRY: This trial was registered in the UMIN clinical trial
      registry (UMIN000006347).

PMID- 30106267
TI  - Successful treatment of psychosis in dentatorubral-pallidoluysian atrophy with
      quetiapine: A case report.
AB  - INTRODUCTION: Patients with dentatorubral-pallidoluysian atrophy (DRPLA)
      sometimes elicit psychosis. First-generation antipsychotic drugs have been
      reported to be effective in treating psychotic symptoms associated with the
      disease. However, little information is available on the benefits of second
      generation antipsychotic drugs (SGAs). CASE: We report on a 47-year-old man with
      DRPLA whose psychotic symptoms were effectively treated with quetiapine, one of
      the SGAs. He suffered from delusions, auditory hallucinations, and disorganized
      speech. Initially, other antipsychotic drugs were tried, but were withdrawn
      because of adverse effects before switching to quetiapine. CONCLUSION: Our
      observations add to the notion that some of the SGAs are useful for ameliorating
      psychosis in DRPLA.

PMID- 30106268
TI  - The diagnostic potential of glutathione S-transferase (GST) polymorphisms in
      patients with colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers in the
      world. Despite improvements in screening for early diagnosis, CRC is one of the
      leading causes of cancer deaths. OBJECTIVES: The aim of the study was to
      determine a potential association between the frequency of GSTM1 and GSTT1 null
      genotypes and the risk of CRC in the Polish population. Moreover, we analyzed the
      clinical parameters with the glutathione S-transferase (GST) gene polymorphisms
      in patients with CRC. MATERIAL AND METHODS: The study was conducted on 512
      Caucasians, including 279 patients (105 women and 174 men) with CRC. DNA from
      peripheral blood was extracted and the multiplex polymerase chain reaction (PCR)
      technique was used for glutathione S-transferase theta (GSTT1) and mu (GSTM1)
      gene deletion genotyping. RESULTS: We found no statistically significant
      differences in the frequency of the GST gene polymorphisms in patients with CRC
      and controls. The prevalence of the GSTM1*0 variant in the test subjects was
      higher than in controls (45.9% vs 42.9%; p > 0.05). The frequency of the GSTT1*0
      variant was also higher in patients with CRC compared to the control population
      (21.1% vs 18.9%; p > 0.05). In addition, the effect of the GSTM1 and GSTT1
      polymorphisms on the incidence of CRC was also analyzed. There was a slight, but
      not statistically significant, increase of the risk of colon cancer for the
      GSTM1*0 and GSTT1*0 variants. Moreover, we examined the GST genotype due to the
      cancer TNM classification and the location of the primary tumor. Statistically
      significant differences in the distribution of the GSTT1*0 and GSTT1*1 genotypes
      in both the stage and the location of the primary tumor were observed.
      CONCLUSIONS: It is suggested that the GSTT1 polymorphism may have an impact on
      the severity of the tumor and its location.

PMID- 30106269
TI  - Biocatalyst and Colorimetric/Fluorescent Dual Biosensors of H2O2 Constructed via
      Hemoglobin-Cu3(PO4)2 Organic/Inorganic Hybrid Nanoflowers.
AB  - In this article, the three-dimensional hemoglobin (Hb)-Cu3(PO4)2
      organic/inorganic hybrid nanoflowers (Hb-Cu3(PO4)2 HNFs) self-assembled by
      nanopetals were synthesized via a facile one-pot green synthetic method. The
      compositions and microstructure of the Hb-Cu3(PO4)2 HNFs were well-characterized
      with X-ray diffraction, scanning electron microscopy, transmission electron
      microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared
      spectroscopy, and UV-vis spectrometry, respectively. The as-prepared Hb-Cu3(PO4)2
      HNFs were to be used as a biocatalyst to construct colorimetric/fluorescent dual
      biosensors. The experimental results show that the colorimetric/fluorescent dual
      biosensors exhibited two linear responses in the range of 2-10 ppb and 20-100 ppb
      for H2O2. The colorimetric and fluorescent detection limits were 0.1 and 0.01
      ppb, respectively. Compared with the free Hb, the biocatalytic activity of the Hb
      Cu3(PO4)2 HNFs can be improved for 3-4 times under optimal conditions. The
      sensing performance of these Hb-Cu3(PO4)2 HNF-based dual biosensors can be
      contributed such that the active sites of Hb molecules were more exposed on the
      surface of the Cu3(PO4)2 nanopetals. Second, the unique nanopetal-assembled
      hybrid flowerlike structure was favorable to contact the detected substance with
      the biosensors. The dual biosensors were successfully applied for the
      determination of H2O2 in rainwater, tap water, and waste water samples. These
      results show that the dual biosensors had a potential application in the field of
      medical analysis, environmental monitoring, and food engineering.

PMID- 30106270
TI  - Highly Bendable and Durable Transparent Electromagnetic Interference Shielding
      Film Prepared by Wet Sintering of Silver Nanowires.
AB  - Electromagnetic (EM) wave emissions from wearable or flexible smart display
      devices can cause product malfunction and have a detrimental effect on human
      health. Therefore, EM shielding strategies are becoming increasingly necessary.
      Consequently, herein, we prepared a transparent acrylic polymer-coated/reduced
      graphene oxide/silver nanowire (Ag NW) (A/RGO/SANW) EM interference (EMI)
      shielding film via liquid-to-vapor pressure-assisted wet sintering. The film
      exhibited enhanced Ag NW network formation and antireflection (AR) effects. The
      wet-sintered Ag NW shielding film had a threshold radius of curvature (ROC) of
      0.31 mm at a film thickness of 100 MUm, demonstrating its high flexibility,
      whereas the conventional indium tin oxide (ITO) shielding film had a threshold
      ROC of ~5 mm. The EMI shielding effectiveness (SE) of the A/RGO/SANW multilayer
      film was approximately twice that of the ITO film at a similar relative
      transmittance (84-85%). The optical relative reflectance of the Ag NW layer was
      reduced due to the AR effect, and the visible-light transmittance was
      considerably improved owing to the different refractive indices in the multilayer
      shielding film. Because the acrylic coating layer had a high contact angle, the
      multilayer film exhibited high temperature and humidity durability with little
      change in the SE over 500 h at 85  degrees C and 85% relative humidity. The
      multilayer film comprising wet-sintered Ag NW exhibited high flexibility and
      humidity durability, high shielding performance (more than 24 dB at a relative
      transmittance of 85% or more), and high mass productivity, making it highly
      applicable for use as a transparent shielding material for future flexible
      devices.

PMID- 30106272
TI  - Products of Degradation of Black Phosphorus in Protic Solvents.
AB  - Deterioration of the surface of black phosphorus (BP) caused by ambient
      atmosphere is an undesired process, limiting broader use of BP in many areas. The
      mechanism of BP degradation was explained theoretically, and the oxidized
      materials were thoroughly characterized experimentally. However, the surface
      analysis techniques introduce only a limited insight into the real state of the
      material. Here, we report a thorough analysis of the composition of mixtures
      obtained after a prolonged exposure of suspensions of BP to atmospheric oxygen
      with the aim to further disclosure the processes involved in the decomposition
      process. The results are compared with the predicted structures of the oxidized
      material and confirm the results of the theoretical calculations. The comparison
      of reactivity of BP with reactivity of white phosphorus under similar conditions
      concludes a similar distribution of the products in both cases.

PMID- 30106271
TI  - Dual Fluorophore Containing Efficient Photoinduced Electron Transfer Based
      Molecular Probe for Selective Detection of Cr3+ and PO43- Ions through
      Fluorescence " Turn-On-Off" Response in Partial Aqueous and Biological Medium:
      Live Cell Imaging and Logic Application.
AB  - The present work describes a new photoinduced electron transfer (PET) based
      molecular probe in which naphthalimide (NPI) and anthracene (AN) chromophores are
      linked through a molecular bridge of piperazine and triazole units by the Click
      reaction. A typical meaningful structural variation has made the present probe
      highly selective for Cr3+ ion (limit of detection (LOD), 5.567 * 10-8 M) that
      displayed enhanced, " turn-On" emission (due to the PET- Off photophysical
      mechanism) and naked-eye sensitive bright green color fluorescence in the
      environment of interfering and competitive ions, in Tris-HCl buffer. The minimum
      energy structure obtained through theoretical calculations (density functional
      theory (DFT) and time-dependent (TD)-DFT) revealed a "tub" shape structure for
      probe 10. Upon complexation, the conformation of piperazine fragment changes from
      chair to boat in which the triazole and piperazine units create a cavity to
      tether Cr3+. Moreover, the probe showed excellent biocompatibility and cell
      permeability to sense Cr3+ sensitively in live cells and, thus, holds great
      promise for application in biological and environmental sciences. Additionally,
      the sensitive " Off-On-Off" sensing behavior of probe 10 providing two chemical
      inputs (Cr3+ and PO43-) helps to construct an INHIBIT logic gate. Also the probe
      has been utilized as printing material to decode secret information through the
      Cr3+ ion containing "marker ink" under UV light.

PMID- 30106273
TI  - Implementation of a Reductive Route of One-Carbon Assimilation in Escherichia
      coli through Directed Evolution.
AB  - Endowing biotechnological platform organisms with new carbon assimilation
      pathways is a key challenge for industrial biotechnology. Here we report progress
      toward the construction of formatotrophic Escherichia coli strains. Glycine and
      serine, universal precursors of one-carbon compounds oxidized during
      heterotrophic growth, are produced from formate and CO2 through a reductive
      route. An adaptive evolution strategy was applied to optimize the enzymatic steps
      of this route in appropriate selection strains. Metabolic labeling experiments
      with 13C-formate confirm the redirected carbon-flow. These results demonstrate
      the high plasticity of the central carbon metabolism of E. coli and the
      applicative potential of directed evolution for implementing synthetic pathways
      in microorganisms.

PMID- 30106274
TI  - Core-Multishell Heterostructure with Excellent Heat Dissipation for
      Electromagnetic Interference Shielding.
AB  - Herein, we report high electromagnetic interference (EMI) shielding effectiveness
      of -40 dB in the Ku-band (for a 600 MUm thick film) through a unique core-shell
      heterostructure consisting of a ferritic core (Fe3O4) and a conducting shell
      (multiwalled carbon nanotubes, MWCNTs) supported onto a dielectric spacer (here
      SiO2). In recent times, materials with good flexibility, heat dissipation
      ability, and sustainability together with efficient EMI shielding at minimal
      thickness are highly desirable, especially if they can be easily processed into
      thin films. The resulting composites here shielded EM radiation mostly through
      absorption driven by multiple interfaces provided by the heterostructure. The
      shielding value obtained here is fairly superior among the different polymer
      nanocomposite-based EMI shielding materials. In addition to EMI shielding
      capability, this composite material exhibits outstanding heat dissipation ability
      (72  degrees C to room temperature in less than 90 s) as well as high heat
      sustainability. The composite material retained its EMI shielding property even
      after repeated heat cycles, thereby opening new avenues in the design of
      lightweight, flexible, and sustainable EMI shielding materials.

PMID- 30106275
TI  - Materials Functionalization with Multicomponent Reactions: State of the Art.
AB  - The emergence of neoteric synthetic routes for materials functionalization is an
      interesting phenomenon in materials chemistry. In particular, the union of
      materials chemistry with multicomponent reactions (MCRs) opens a new avenue
      leading to the realm of highly innovative functionalized architectures with
      unique features. MCRs have recently been recognized as considerable part of the
      synthetic chemist's toolbox due to their great efficiency, inherent molecular
      diversity, atom and pot economy along with operational simplicity. Also, MCRs can
      improve E-factor and mass intensity as important green chemistry metrics. By
      rational tuning of the materials, as well as the MCRs, wide ranges of
      functionalized materials can be produced with tailorable properties that can play
      important roles in the plethora of applications. To date, there has not reported
      any exclusive review of a materials functionalization with MCRs. This critical
      review highlights the state-of-the-art on the one-pot functionalization of
      carbonaceous and siliceous materials, polysaccharides, proteins, enzymes,
      synthetic polymers, etc., via diverse kind of MCRs like Ugi, Passerini, Petasis,
      Khabachnik-Fields, Biginelli, and MALI reactions through covalent or noncovalent
      manners. Besides the complementary discussion of synthetic routes, superior
      properties and detailed applicability of each functionalized material in modern
      technologies are discussed. Our outlook also emphasizes future strategies for
      this unprecedented area and their use as materials for industrial implementation.
      With no doubt, MCRs-functionalization of materials bridges the gap between
      materials science domain and applied chemistry.

PMID- 30106276
TI  - Flexible THV/COC Piezoelectret Nanogenerator for Wide-Range Pressure Sensing.
AB  - Flexible pressure sensors possess promising applications in artificial electronic
      skin, intelligence robot, wearable health monitoring, flexible physiological
      signal sensing, etc. Herein, we design a flexible pressure sensor with robust
      stability, high sensitivity, and large linear pressure region on the basis of
      tetrafluoroethylene-hexafluoropropylene-vinylide (THV)/cyclic olefin copolymer
      (COC) piezoelectret nanogenerator. According to the theoretical analysis for
      piezoelectret nanogenerators with imbalanced charge distribution, THV and COC are
      utilized to promote the electric field inside the piezoelectret for output
      voltage enhancement. Meanwhile, the compression property of the piezoelectret
      nanogenerator is facilely tuned. Owing to high inner electric field and optimized
      compression property, the THV/COC piezoelectret nanogenerator exhibits a high
      sensitivity of 30 mV/kPa, which is 10 times higher than that of the traditional
      cellular polypropylene piezoelectret. Simultaneously, the linear pressure region
      reaches 150 kPa with excellent linearity ( R2 = 0.99963). The device is
      demonstrated to realize wearable pressure sensing with a wide pressure range from
      finger typing to fist hammering. This study presents a fabrication strategy for
      piezoelectret nanogenerators with high sensitivity and large linear pressure
      region, paving the way for development of wearable and flexible pressure sensing
      networks.

PMID- 30106277
TI  - Correction to Preventing Plasmon Coupling between Gold Nanorods Improves the
      Sensitivity of Photoacoustic Detection of Labeled Stem Cells in Vivo.

PMID- 30106278
TI  - Hybrid of Resveratrol and Glucosamine: An Approach To Enhance Antioxidant Effect
      against DNA Oxidation.
AB  - Resveratrol exhibits various pharmacological activities, which are dependent upon
      phenolic hydroxyl groups. In this work, glucosamine, lipoic acid, or
      adamantanamine moiety was applied for attaching to ortho-position of hydroxyl
      group in resorcinol moiety of resveratrol (known as position-2). Antioxidant
      effects of the obtained hybrids were characterized using DNA oxidative systems
      mediated by *OH, Cu2+/glutathione (GSH), and 2,2'-azobis(2
      amidinopropanehydrochloride) (AAPH), respectively. The glucosyl-appended imine
      and amine at position-2 of resveratrol were found to show higher inhibitory
      effects than other resveratrol derivatives against AAPH-induced DNA oxidation.
      The antioxidative effect was quantitatively expressed by stoichiometric factor (
      n, the number of radical-propagation terminated by one molecule of antioxidant).
      The stoichiometric factors of glucosyl-appended imine and amine of resveratrol
      increased to 4.74 (for imine) and 4.97 (for amine), respectively, higher than
      that of resveratrol (3.70) and glucoside of resveratrol (3.49). It was thereby
      concluded that the combination of resveratrol with glucosamine at position-2
      represented a novel pathway for modifying resveratrol structure in the protection
      of DNA against peroxyl radical-mediated oxidation.

PMID- 30106279
TI  - Reactive Oxygen Species-Responsive Nanoparticles Based on PEGlated Prodrug for
      Targeted Treatment of Oral Tongue Squamous Cell Carcinoma by Combining
      Photodynamic Therapy and Chemotherapy.
AB  - In this study, a reactive oxygen species (ROS)-responsive nanoparticle system was
      designed for combining photodynamic therapy (PDT) and chemotherapy for oral
      tongue squamous cell carcinoma (OTSCC)-targeted treatment. A PEGlated prodrug
      (RPTD) of doxorubicin (DOX) via thioketal linkage and cRGD peptide modification
      was synthesized and then used to prepare nanoparticles for encapsulating
      photosensitizer hematoporphyrin (HP). Thus, the obtained HP-loaded RPTD (RPTD/HP)
      nanoparticles had a regular spherical shape and small size, approximately 180 nm.
      The RPTD/HP nanoparticles showed a remarkable PDT efficiency and successfully
      induced ROS generation upon laser irradiation both in vitro and in vivo. DOX
      exhibited significant ROS-responsive release property from RPTD/HP nanoparticles
      because of the rupture of the thioketal linker. In OTSCC cells, RPTD/HP
      nanoparticles were efficiently internalized and showed potent effects on cell
      growth inhibition and apoptosis induction after laser irradiation. In OTSCC tumor
      bearing mice, RPTD/HP nanoparticles displayed excellent tumor-targeting ability
      and notably suppressed tumor growth through multiple mechanisms after local laser
      irradiation. Taken together, we supplied a novel therapeutic nanosystem for OTSCC
      treatment through combining PDT and chemotherapy.

PMID- 30106280
TI  - Comparing Protonolysis and Transmetalation Reactions: Microcalorimetric Studies
      of C-AuI Bonds in [AuRL] Complexes.
AB  - The protonolysis of C-Au bonds in [AuRL] organometallic complexes has been
      studied by calorimetry for 12 R groups. The experimental data have been combined
      with density functional theory calculations to obtain bond dissociation energy
      (BDE) values. The C-Au BDE values show a good correlation with the corresponding
      isolobal C-H BDE values. The heat released in the protonolysis of [AuRL] has also
      been measured for R = Ph and L = P(OPh)3, PPh3, PMe3, PCy3, and IPr, and these
      values strongly depend on the trans influence of L because of the mutual
      destabilization of the L-Au and Au-C bonds. The enthalpies of the transmetalation
      reaction [AuR(PPh3)] + SnIBu3 -> [AuI(PPh3)] + SnRBu3 for seven R groups have
      been measured and compared with those of the corresponding [AuR(PPh3)]
      protonolysis.

PMID- 30106281
TI  - Electronic Structure Investigation of the Bulk Properties of Uranium-Plutonium
      Mixed Oxides (U, Pu)O2.
AB  - We present electronic structure calculations of bulk properties of (U, Pu)O2, in
      the whole Pu content range for which only very few experimental data are
      available. We use DFT+U and the vdW-DF functional in order to take into account
      the strong 5f electron correlations and nonlocal correlations. We investigate
      structural, elastic, electronic, and energetic properties of (U, Pu)O2 in the
      approximation of the ideal solid solution as described by the special quasirandom
      structures (SQS) method. The results on electronic properties highlight the
      narrowing of the band gap due to the mixing of UO2 and PuO2. Results on the
      mixing enthalpy are used to describe the phase stability of (U, Pu)O2 solid
      solutions, using both SQS configurations and a parametric method. In particular,
      the issue of an ideal solid solution on a limited supercell size is discussed.

PMID- 30106282
TI  - Nucleic Acid Photolysis by UV254 and the Impact of Virus Encapsidation.
AB  - Determining the influence of higher order structure on UVC photolysis will help
      inform predictions of nucleic acid fate and microorganism inactivation. We
      measured the direct UV254 photolysis kinetics of four model viral genomes
      composed of single-stranded and double-stranded RNA (ssRNA and dsRNA,
      respectively), as well as single-stranded and double-stranded DNA (ssDNA and
      dsDNA, respectively), in ultrapure water, in phosphate buffered saline (PBS), and
      encapsidated in their native virus particles. The photolysis rate constants of
      naked nucleic acids measured by qPCR (RT-qPCR for RNA) and normalized by the
      number of bases measured in a particular sequence exhibited the following trend:
      ssDNA > ssRNA ~ dsDNA > dsRNA. In PBS, naked ssRNA bases reacted, on average, 24*
      faster than the dsRNA bases, whereas naked ssDNA bases reacted 4.3* faster than
      dsDNA bases. Endogenous indirect photolysis involving 1O2 and .OH was ruled out
      as a major contributing factor in the reactions. A comparison of our measured
      rate constants with rate constants reported in the literature shows a general
      agreement among the nucleic acid UV254 direct photolysis kinetics. Our results
      underscore the high resistance of dsRNA to UVC photolysis and demonstrate the
      role that nucleic acid structure and solution chemistry play in photoreactivity.

PMID- 30106283
TI  - Fecal Fingerprints of Enteric Pathogen Contamination in Public Environments of
      Kisumu, Kenya, Associated with Human Sanitation Conditions and Domestic Animals.
AB  - Young children are infected by a diverse range of enteric pathogens in high
      disease burden settings, suggesting pathogen contamination of the environment is
      equally diverse. This study aimed to characterize across- and within-neighborhood
      diversity in enteric pathogen contamination of public domains in urban informal
      settlements of Kisumu, Kenya, and to assess the relationship between pathogen
      detection patterns and human and domestic animal sanitation conditions. Microbial
      contamination of soil and surface water from 166 public sites in three Kisumu
      neighborhoods was measured by enterococcal assays and quantitative reverse
      transcription polymerase chain reaction (qRT-PCR) for 19 enteric pathogens.
      Regression was used to assess the association between observed sanitary
      indicators of contamination with enterococci and pathogen presence and
      concentration, and pathogen diversity. Seventeen types of pathogens were detected
      in Kisumu public domains. Enteric pathogens were codetected in 33% of soil and
      65% of surface water samples. Greater pathogen diversity was associated with the
      presence of domestic animal feces but not with human open defecation,
      deteriorating latrines, flies, or disposal of human feces. Sanitary conditions
      were not associated with enterococcal bacteria, specific pathogen concentrations,
      or "any pathogen". Young children played at 40% of observed sites. Managing
      domestic animal feces may be required to reduce enteric pathogen environmental
      contamination in high-burden settings.

PMID- 30106284
TI  - Role of Extracellular Polymeric Substances in a Methane Based Membrane Biofilm
      Reactor Reducing Vanadate.
AB  - For the first time, we demonstrated vanadate (V(V)) reduction in a membrane
      biofilm reactor (MBfR) using CH4 as the sole electron donor. The V(V)-reducing
      capability of the biofilm kept increasing, with complete removal of V(V) achieved
      when the influent surface loading of V(V) was 363 mg m-2 day-1. Almost all V(V)
      was reduced to V(IV) precipitates, which is confirmed by a scanning electron
      microscope coupled to energy dispersive X-ray spectroscopy (SEM-EDS) and X-ray
      photoelectron spectroscopy (XPS). Microbial community analysis revealed that
      denitrifiers Methylomonas and Denitratisoma might be the main genera responsible
      for V(V) reduction. The constant enrichment of Methylophilus suggests that the
      intermediate (i.e., methanol) from CH4 metabolism might be used as the electron
      carriers for V(V) bioreduction. Intrusion of V(V) (2-5 mg/L, at the surface
      loading of 150-378 mg m-2 day-1) into the biofilm stimulated the secretion of
      extracellular polymeric substances (EPS), but high loading of V(V) (10 mg/L, at
      the surface loading of 668 mg m-2 day-1) decreased the amount of EPS. Metagenomic
      prediction analysis established the strong correlation between the secretion of
      EPS and the microbial metabolism associated with V(V) reduction, tricarboxylic
      acid cycle (TCA) cycle, methane oxidation, and ATP production, and EPS might
      relieve the oxidative stress induced by high loading of V(V). Colorimetric
      determination and a three-dimensional excitation-emission matrix (3D-EEM) showed
      that tryptophan and humic acid-like substances might play important roles in
      microbial cell protection and V(V) binding. Fourier transform infrared (FTIR)
      spectroscopy identified hydroxyl (-OH) and carboxyl (COO-) groups in EPS as the
      candidate functional groups for binding V(V).

PMID- 30106285
TI  - A Path to Ultraselectivity: Support Layer Properties To Maximize Performance of
      Biomimetic Desalination Membranes.
AB  - Reverse osmosis (RO) has become a premier technology for desalination and water
      purification. The need for increased selectivity has incentivized research into
      novel membranes, such as biomimetic membranes that incorporate the perfectly
      selective biological water channel aquaporin or synthetic water channels like
      carbon nanotubes. In this study, we consider the performance of composite
      biomimetic membranes by projecting water permeability, salt rejection, and
      neutral-solute retention based on the permeabilities of the individual
      components, particularly the water channel, the amphiphilic bilayer matrix, and
      potential support layers that include polymeric RO, nanofiltration (NF), and
      porous ultrafiltration membranes. We find that the support layer will be crucial
      in the overall performance. Selective, relatively low-permeability supports
      minimize the negative impact of defects in the biomimetic layer, which are
      currently the main performance-limiting factor for biomimetic membranes. In
      particular, RO membranes as support layers would enable >99.85% salt rejection at
      ~10000-fold greater biomimetic-layer defect area than for porous supports. By
      fundamentally characterizing neutral-solute permeation through RO and NF
      membranes, we show that RO membranes as support layers would enable high
      rejection of organic pollutants based on molecular size, overcoming the rapid
      permeation of hydrophobic solutes through the biomimetic layer. A biomimetic
      membrane could also achieve exceptionally high boron rejections of ~99.7%, even
      with 1% defect area in the biomimetic layer. We conclude by discussing the
      implications of our findings for biomimetic membrane design.

PMID- 30106286
TI  - Translating Catalysis to Chemiresistive Sensing.
AB  - Activating molecules or functional groups with high chemoselectivity in complex
      environments is the central goal of transition-metal-based catalysis. Promoting
      strong interactions between a selected substrate and a catalytic system can also
      be used to create highly selective and customizable sensors, and these concepts
      are widely recognized for enzymatic processes. We demonstrate the successful
      translation of organometallic reactions to sensing capability. Specifically, we
      have developed single-walled carbon nanotube (SWCNT) chemiresistive sensors for
      the highly selective detection of acrylates using conditions for the aerobic
      oxidative Heck reaction. The sensors mirror the catalytic processes and
      selectively respond to electron-deficient alkenes by adapting a catalytic
      reaction system to modulate the doping levels in carbon nanotubes. The sensors
      readily detect acrylates at parts per million (ppm) levels in untreated air. The
      concepts presented here are generally applicable and can guide future sensor
      development based upon known catalytic processes.

PMID- 30106288
TI  - Minor Nortriterpenoids from the Twigs and Leaves of Rhododendron latoucheae.
AB  - A hyphenated NMR technique (analytical HPLC with a DAD connected to MS, SPE, and
      NMR) has proven effective for the full structural analysis and identification of
      minor natural products in complex mixtures. Application of this hyphenated
      technique to the CH2Cl2-soluble fraction of Rhododendron latoucheae led to the
      identification of 15 new minor ursane-type 28-nortriterpenoids (1-15). Compounds
      1 and 12 inhibited HSV-1 with IC50 values of 6.4 and 0.4 MUM, respectively.

PMID- 30106289
TI  - Antitumor Activity of Diterpenoids from Jatropha gossypiifolia: Cell Cycle Arrest
      and Apoptosis-Inducing Activity in RKO Colon Cancer Cells.
AB  - Nine new minor diterpenoids, jatrogossones A-I (1-9), and six known analogues (10
      15) were separated from an extract of the branches and leaves of Jatropha
      gosspiifolia. Compounds 4-6 and 10, possessing a 5/11 fused-ring skeleton, and 8,
      9, and 13, with a 5/9/5 fused-ring skeleton, represent rare diterpenoid skeletons
      that have been found only in compounds isolated from plants of the Jatropha
      genus. The absolute configurations of 1-10 were defined by using a combination of
      electronic circular dichroism data analysis and single-crystal X-ray diffraction
      data. The cytotoxicity of the diterpenoids was evaluated using RKO and LOVO colon
      cancer cells in which regenerating islet-derived protein 3-alpha (Reg3A) is
      highly expressed. Compound 12 exhibited cytotoxicity against RKO colon cancer
      cells with an IC50 value of 2.6 MUM. Morphological features of apoptosis and
      antimigration activities were evaluated in 12-treated RKO cells. Compound 12
      effectively induced apoptosis of RKO, which was associated with G2/M-phase cell
      cycle arrest. Flow cytometric analysis showed that the treatment by 12
      significantly induced RKO cell apoptosis in a dose-dependent manner.

PMID- 30106290
TI  - Targeted Isolation of Neuroprotective Dicoumaroyl Neolignans and Lignans from
      Sageretia theezans Using in Silico Molecular Network Annotation Propagation-Based
      Dereplication.
AB  - The integration of LC-MS/MS molecular networking and in silico MS/MS
      fragmentation is an emerging method for dereplication of natural products. In the
      present study, a targeted isolation of natural products using a new in silico
      based annotation tool named Network Annotation Propagation (NAP) is described.
      NAP improves accuracy of in silico fragmentation analyses by reranking candidate
      structures based on the network topology from MS/MS-based molecular networking.
      Annotation for the MS/MS spectral network of the Sageratia theezans twig extract
      was performed using NAP, and most molecular families within the network,
      including the known triterpenoids 1-7, could be putatively annotated, without
      relying on any previous reports of molecules from this species. Based on the in
      silico dereplication results, molecules were prioritized for isolation. In total,
      six dicoumaroyl 8- O-4' neolignans (8-13) and three dicoumaroyl lignans (14-16)
      were isolated from the twigs of S. theezans and structurally characterized by
      spectroscopic analyses. Isolates were evaluated for their neuroprotective
      activity, and compounds 14-16 showed potent protective effects against glutamate
      induced oxidative stress in mouse HT22 cells at a concentration of 12.5 MUM.

PMID- 30106291
TI  - Staurosporine Derivatives Generated by Pathway Engineering in a Heterologous Host
      and Their Cytotoxic Selectivity.
AB  - Two new staurosporine derivatives, staurosporines M1 and M2 (4 and 5), in
      addition to five previously reported metabolites (1-3, 6, and 7), were generated
      by the heterologous expression of engineered spc gene clusters in Streptomyces
      coelicolor M1146. The structures of these derivatives were determined by a
      combination of spectroscopic methods and CD measurement. Compounds 1, 2, 4, and 5
      showed effective activities against three tumor cell lines (HCT-116, K562, and
      Huh 7.5), and 3 was active against HCT-116 and K562 cells. In addition, compounds
      3 and 5 showed undetectable toxicity up to 100 MUM toward the normal hepatic cell
      line LO2. Based on the IC50 values, their structure and activity relationships
      are discussed.

PMID- 30106293
TI  - Candidatus Liberibacter asiaticus Minimally Alters Expression of Immunity and
      Metabolism Proteins in Hemolymph of Diaphorina citri, the Insect Vector of
      Huanglongbing.
AB  - Huanglongbing (HLB), also known as citrus greening disease, is the most serious
      disease of citrus plants. It is associated with the Gram-negative bacterium '
      Candidatus Liberibacter asiaticus' ( CLas), which is transmitted between host
      plants by the hemipteran insect vector Diaphorina citri in a circulative,
      propagative manner involving specific interactions with various insect tissues
      including the hemolymph, fluid that occupies the body cavity akin to insect
      blood. High resolution quantitative mass spectrometry was performed to
      investigate the effect of CLas exposure on D. citri hemolymph at the proteome
      level. In contrast to the broad proteome effects on hundreds of proteins and a
      diverse array of metabolic pathways previously reported in gut and whole insect
      proteome analyses, the effect of CLas on the hemolymph was observed to be highly
      specific, restricted to key immunity and metabolism pathways, and lower in
      magnitude than that previously observed in the whole insect body and gut.
      Vitellogenins were abundantly expressed and CLas-responsive. Gene-specific RNA
      expression analysis suggests that these proteins are expressed in both male and
      female insects and may have roles outside of reproductive vitellogenesis.
      Proteins for fatty acid synthesis were found to be up-regulated, along with
      metabolic proteins associated with energy production, supported at the organismal
      level by the previously published observation that D. citri individuals
      experience a higher level of hunger when reared on CLas-infected plants.
      Prediction of post-translational modifications identified hemolymph proteins with
      phosphorylation and acetylation upon CLas exposure. Proteins derived from the
      three most prominent bacterial endosymbionts of the psyllid were also detected in
      the hemolymph, and several of these have predicted secretion signals. A DNAK
      protein, the bacterial HSP70, detected in the hemolymph expressed from Wolbachia
      pipientis was predicted to encode a eukaryotic nuclear localization signal. Taken
      together, these data show specific changes to immunity and metabolism in D. citri
      hemolymph involving host and endosymbiont proteins. These data provide a novel
      context for proteomic changes seen in other D. citri tissues in response to CLas
      and align with organismal data on the effects of CLas on D. citri metabolism and
      reproduction.

PMID- 30106294
TI  - Antibacterial Prenylated Isoflavonoids from the Stems of Millettia extensa.
AB  - The first phytochemical investigation of the stem extract of Millettia extensa
      resulted in the isolation and identification of six new isoflavones, millexatins
      A-F (1-6), together with 16 known compounds. The structures of these new
      compounds were determined on the basis of their spectroscopic data. Millexatin A
      (1) is a rare isoflavone containing three isoprenyl units on a modified A ring.
      Compounds 1, 6, 10, 11, and 14 displayed promising antibacterial activity with
      MIC values of 2-8 MUg/mL.

PMID- 30106292
TI  - Discovery of a Locally and Orally Active CXCL12 Neutraligand (LIT-927) with Anti
      inflammatory Effect in a Murine Model of Allergic Airway Hypereosinophilia.
AB  - We previously reported Chalcone-4 (1) that binds the chemokine CXCL12, not its
      cognate receptors CXCR4 or CXCR7, and neutralizes its biological activity.
      However, this neutraligand suffers from limitations such as poor chemical
      stability, solubility, and oral activity. Herein, we report on the discovery of
      pyrimidinone 57 (LIT-927), a novel neutraligand of CXCL12 which displays a higher
      solubility than 1 and is no longer a Michael acceptor. While both 1 and 57 reduce
      eosinophil recruitment in a murine model of allergic airway hypereosinophilia, 57
      is the only one to display inhibitory activity following oral administration.
      Thereby, we here describe 57 as the first orally active CXCL12 neutraligand with
      anti-inflammatory properties. Combined with a high binding selectivity for CXCL12
      over other chemokines, 57 represents a powerful pharmacological tool to
      investigate CXCL12 physiology in vivo and to explore the activity of chemokine
      neutralization in inflammatory and related diseases.

PMID- 30106295
TI  - Regioselective Access to 3-Aryl-1-aminoisoquinolines via Nickel(I)-Catalyzed C-C
      and C-N Cascade Coupling Reactions from the Substituted 2
      (Cyanomethyl)benzonitriles.
AB  - A novel and regioselective Ni(I) catalyzed C-C and C-N cascade coupling reactions
      has been developed. The cascade furnishes atom-economic access to 40 3-aryl-1
      aminoisoquinolines. The regioselectivity of C(sp3)-cyano group over C(sp2)-cyano
      group was revealed and supported by mechanism studies as well as the preliminary
      density functional theory (DFT) calculations.

PMID- 30106296
TI  - Antiproliferative Alkaloids from Alangium longiflorum, an Endangered Tropical
      Plant Species.
AB  - Alangium longiflorum is currently in extinction crisis, which will likely
      severely hamper further phytochemical investigation of this plant species from
      new collections. A crude extract of leaves of A. longiflorum (N33539), collected
      for the U.S. National Cancer Institute in 1989, showed potent cancer cell line
      antiproliferative activity. A phytochemical study resulted in the isolation of 17
      secondary metabolites, including two new tetrahydroisoquinoline alkaloids, 8
      hydroxytubulosine (1) and 2'- O- trans-sinapoylisoalangiside (2), as well as a
      new sinapolyloxylupene derivative (3). Using in-house assays and NCI-60 panel
      screening, compound 1 displayed broad-spectrum inhibitory activity at
      submicromolar levels against most tested tumor cell lines, except for drug
      transporter-overexpressing cells. Compound 1 caused accumulation of sub-G1 cells
      with no effect on cell cycle progression, suggesting that this substance is an
      apoptosis inducer.

PMID- 30106297
TI  - Structurally Diverse Highly Oxygenated Triterpenoids from the Roots of Ailanthus
      altissima and Their Cytotoxicity.
AB  - Ten new triterpenoids, ailanaltiolides A-J (1-10), and three known analogues (11
      13) were isolated from the roots of Ailanthus altissima. Compounds 1-7 are
      apotirucallane-type, compounds 8 and 9 are tirucallane-type, and compound 10 is a
      trinordammarane-type triterpenoid. This is the first study indicating the genus
      Ailanthus as a potential source for apotirucallane derivatives, which contain an
      alpha,beta-unsaturated-epsilon-lactone A-ring and diversely modified C-17 side
      chains. Spectroscopic data interpretation, electronic circular dichroism
      analysis, and X-ray crystallographic data defined the structures and absolute
      configurations of these triterpenoids. Compounds 2, 7, and 8 showed cytotoxicity
      against four tumor cell lines (HeLa, 786-O, HepG2, and A549). In particular,
      compound 2 exhibited the highest activity against 786-O cells with an IC50 value
      of 8.2 MUM in vitro.

PMID- 30106298
TI  - Substrate-Controlled Generation of 3-Sulfonylated 1-Indenones and 3-Arylated ( Z)
      Indenes via Cu-Catalyzed Radical Cyclization Cascades of o-Alkynylbenzonitriles.
AB  - Substrate-controlled generation of 3-sulfonylated 1-indenones and 3-arylated ( Z)
      indenes through radical cyclization cascades of o-alkynylbenzonitriles with
      sulfonyl hydrazides was established by combining copper(II) with tert-butyl
      hydroperoxide (TBHP) as a catalytic oxidative system. With the installation of
      the aryl group (R1) into the alkynyl unit, sulfonyl radicals triggered addition
      cyclization cascades to access 3-sulfonylated 1-indenones with good yields by
      using a Cu/TBHP system, whereas a series of new functionalized 3-arylated ( Z)
      indenes were obtained in good yields when o-alkynylbenzonitriles bearing the
      alkyl group in the alkynyl unit were subjected with arylsulfonyl hydrazides with
      an electron-rich nature under the above conditions.

PMID- 30106299
TI  - Understanding the Twisted Structure of Amyloid Fibrils via Molecular Simulations.
AB  - Accumulation and aggregation of amyloid are associated with the pathogenesis of
      many human diseases, such as Alzheimer's disease and Type 2 diabetes mellitus.
      Therefore, a quantitative understanding of the molecular mechanisms causing
      different aggregated structures and biomechanical properties of amyloid fibrils
      could shed some light into the progression of these diseases. In this work, we
      develop coarse-grained molecular dynamics (CGMD) models to simulate the dynamic
      self-assembly of two types of amyloids (amylin and amyloid beta (Abeta)). We
      investigate the structural and mechanical properties of different types of
      aggregated amyloid fibrils. Our simulations demonstrate that amyloid fibrils
      could result from longitudinal growth of protofilament bundles, confirming one of
      the hypotheses on the fibril formation. In addition, we find that the persistence
      length of amylin fibrils increases concurrently with their pitch length,
      suggesting that the bending stiffness of amylin fibrils becomes larger when the
      amylin fibrils are less twisted. Similar results are observed for Abeta fibrils.
      These findings quantify the connection between the structural and the
      biomechanical properties of the fibrils. The CGMD models developed in this work
      can be potentially used to examine efficacy of anti-aggregation drugs, which
      could help in developing new treatments.

PMID- 30106300
TI  - Direct Substitution of Secondary and Tertiary Alcohols To Generate Sulfones under
      Catalyst- and Additive-Free Conditions.
AB  - An environmentally benign protocol that affords propargylic sulfones containing
      highly congested carbon centers from easily accessible alcohols and sulfinic
      acids with water as the only byproduct is reported. The reaction proceeded via an
      in situ dehydrative cross-coupling process by taking advantage of the synergetic
      actions of multiple hydrogen bonds rather than relying on an external catalyst
      and/or additives to achieve high product distribution.

PMID- 30106301
TI  - Revealing Optical Transitions and Carrier Recombination Dynamics within the Bulk
      Band Structure of Bi2Se3.
AB  - Bismuth selenide (Bi2Se3) is a prototypical 3D topological insulator whose Dirac
      surface states have been extensively studied theoretically and experimentally.
      Surprisingly little, however, is known about the energetics and dynamics of
      electrons and holes within the bulk band structure of the semiconductor. We use
      mid-infrared femtosecond transient reflectance measurements on a single nanoflake
      to study the ultrafast thermalization and recombination dynamics of photoexcited
      electrons and holes within the extended bulk band structure over a wide energy
      range (0.3 to 1.2 eV). Theoretical modeling of the reflectivity spectral line
      shapes at 10 K demonstrates that the electrons and holes are photoexcited within
      a dense and cold electron gas with a Fermi level positioned well above the bottom
      of the lowest conduction band. Direct optical transitions from the first and the
      second spin-orbit split valence bands to the Fermi level above the lowest
      conduction band minimum are identified. The photoexcited carriers thermalize
      rapidly to the lattice temperature within a couple of picoseconds due to optical
      phonon emission and scattering with the cold electron gas. The minority carrier
      holes recombine with the dense electron gas within 150 ps at 10 K and 50 ps at
      300 K. Such knowledge of interaction of electrons and holes within the bulk band
      structure provides a foundation for understanding how such states interact
      dynamically with the topologically protected Dirac surface states.

PMID- 30106302
TI  - Cyclization of 2-Biphenylthiols to Dibenzothiophenes under PdCl2/DMSO Catalysis.
AB  - A palladium-catalyzed synthesis of dibenzothiophenes from 2-biphenylthiols is
      described. This highly efficient reaction employs a simple PdCl2/DMSO catalytic
      system, in which PdCl2 is the sole metal catalyst and DMSO functions as an
      oxidant and solvent. This transformation has broad substrate scope and
      operational simplicity and proceeds in high yield. The synthetic utility was
      demonstrated by the facile synthesis of helical dinapthothiophene 3 and an
      eminent organic semiconductor DBTDT 4. Importantly, highly strained
      trithiasumanene 5, a buckybowl of considerable synthetic challenge, was observed
      under this catalytic system.

PMID- 30106303
TI  - Organocatalytic Enantioselective Cycloetherifications Using a Cooperative Cation
      Binding Catalyst.
AB  - A highly enantioselective cycloetherification strategy for the straightforward
      synthesis of enantioenriched tetrahydrofurans, tetrahydropyrans, and oxepanes
      using Song's cation-binding oligoEG catalyst and KF as the base is demonstrated.
      A wide range of epsilon-, zeta-, and eta-hydroxy-alpha,beta-unsaturated ketones
      were cyclized to the corresponding five-, six-, and seven-membered chiral
      oxacycles with high enantiopurity. This remarkably successful catalysis can be
      ascribed to systematic cooperative cation-binding catalysis in a densely confined
      supramolecular chiral cage generated in situ from the chiral catalyst, substrate,
      and KF.

PMID- 30106304
TI  - Anthranosides A-C, Anthranilate Derivatives from a Sponge-Derived Streptomyces
      sp. CMN-62.
AB  - Three new derivatives, anthranosides A-C (1-3), were discovered from a marine
      sponge-derived actinomycete Streptomyces sp. CMN-62. Their structures including
      absolute configurations were elucidated using MS and NMR spectroscopic data, X
      ray single-crystal diffraction analysis, and chemical synthesis. Compounds 1 and
      2 are epimers composed by linking the anthranilate unit to the fructofuranose
      moiety via a carbon-nitrogen bond, while 3 possessed a unique indole-containing
      scaffold. All compounds were tested for cytotoxicity, anti-influenza H1N1 virus,
      and NFkappaB inhibitory activities, and 3 showed anti-influenza activity. A
      possible Amadori rearrangement-based biosynthetic pathway was proposed to
      generate compounds 1-3.

PMID- 30106305
TI  - Expanding the Chemical Space of Nonribosomal Peptide Synthetase-like Enzymes by
      Domain and Tailoring Enzyme Recombination.
AB  - The potential of tailoring enzymes in combination with engineered hybrid
      nonribosomal peptide synthetase-like enzymes was explored and resulted in
      methylated and prenylated forms of novel natural products, highlighting the
      possibilities and limitations of this approach.

PMID- 30106306
TI  - Mechanism and Origins of Regio- and Stereoselectivities in Iridium-Catalyzed
      Isomerization of 1-Alkenes to trans-2-Alkenes.
AB  - Density functional theory calculations were performed to investigate the iridium
      catalyzed isomerization of 1-alkenes to trans-2-alkenes. The computations show
      that the originally proposed pi-allyl mechanism is kinetically unfeasible. A
      metal-ligand cooperative mechanism was suggested to account for the experimental
      results. The reaction was found to begin with the C(sp2)-H oxidative addition of
      the pyridine ligand to give the Ir(III) hydride intermediate, from which the
      isomerization further takes place via the insertion/elimination pathway.

PMID- 30106307
TI  - Rational Druggability Investigation Toward Selection of Lead Molecules: Impact of
      the Commonly Used Spices on Inflammatory Diseases.
AB  - Herbal remedies and phytochemicals have been used in traditional medicine. Most
      of the herbs used in human diet have some major effective elements that can
      affect various pathways in the human body and play a therapeutic role in healing
      disorders or diseases. Among the inflammatory diseases, worldwide common
      disorders possess well-known pathways that can be controlled by diet and
      behavior. There are some well-established targets that are used for anti
      inflammatory drugs like cyclooxygenase type 1 and 2 (COX-1 and COX-2),
      lipoxygenase, prostaglandin D2 receptor, DP1, CRTH2, and so on. In this article,
      we investigated the role of phytochemicals, extracted from different commonly
      used spices in the food industry, in preventing or healing the inflammatory
      disorders. The ability of such bioactives to inhibit COX-2 enzyme has been
      investigated and compared with marketed selective and nonselective NSAIDs,
      aspirin and celecoxib. Thereafter, the pharmacokinetic and pharmacodynamic
      properties of such ingredients have been evaluated for their druggability
      potential. The results indicated that piperine showed the best ADME (absorption,
      distribution, metabolism, and excretion) and toxicity profiles among all
      bioactives. Also, it possessed better affinity value, -7.80518 kcal/mol and
      energy binding -85.08 kcal/mol, in inhibition of COX-2 with PDB Id: 1CVU rather
      than other compounds and significantly the higher dock score than aspirin, close
      to celecoxib. Therefore, piperine has been suggested to be used as the major
      ingredient in daily diet as a potent anti-inflammatory and anticancer agent.

PMID- 30106308
TI  - Geoelectrodes and Fuel Cells for Simulating Hydrothermal Vent Environments.
AB  - Gradients generated in hydrothermal systems provide a significant source of free
      energy for chemosynthetic life and may play a role in present-day habitability on
      ocean worlds. Electron/proton/ion gradients, particularly in the context of
      hydrothermal chimney structures, may also be relevant to the origins of life on
      Earth. Hydrothermal vents are similar in some ways to typical fuel cell devices:
      redox/pH gradients between seawater and hydrothermal fluid are analogous to the
      fuel cell oxidant and fuel reservoirs; the porous chimney wall is analogous to a
      separator or ion-exchange membrane and is also a conductive path for electrons;
      and the hydrothermal minerals are analogous to electrode catalysts. The modular
      and scalable characteristics of fuel cell systems make for a convenient planetary
      geology test bed in which geologically relevant components may be assembled and
      investigated in a controlled simulation environment. We have performed fuel cell
      experiments and electrochemical studies to better understand the catalytic
      potential of seafloor minerals and vent chimneys, using samples from a black
      smoker vent chimney as an initial demonstration. In a fuel cell with Na+
      conducting Nafion(r) membranes and liquid fuel/oxidant reservoirs (simulating the
      vent environment), the black smoker mineral catalyst in the membrane electrode
      assembly was effective in reducing O2 and oxidizing sulfide. In a H2/O2 polymer
      electrolyte membrane (PEM) fuel cell with H+-conducting Nafion membranes, the
      black smoker catalyst was effective in reducing O2 but not in oxidizing H2. These
      fuel cell experiments accurately simulated the redox reactions that could occur
      in a geological setting with this particular catalyst, and also tested whether
      the minerals are sufficiently active to replace a commercial fuel cell catalyst.
      Similar experiments with other geocatalysts could be utilized to test which redox
      reactions could be driven in other hydrothermal systems, including hypothesized
      vent systems on other worlds.

PMID- 30106310
TI  - Determining a Reasonable Range of Relative Numerical Tolerance Values for
      Simulating Deterministic Models of Biochemical Reactions.

PMID- 30106309
TI  - Lactate transporters as therapeutic targets in cancer and inflammatory diseases.
AB  - INTRODUCTION: Inflammation is associated with the accumulation of lactate at
      sites of tumor-growth and inflammation. Lactate initiates tissue-responses
      contributing to disease. We discuss the potential of targeting lactate
      transporters in the treatment of cancer and inflammatory conditions. Areas
      covered: Lactate is the end product of glycolysis, often considered a waste
      metabolite but also a fuel for oxidative cells. It is however an active signaling
      molecule with immunomodulatory and angiogenic properties. They are the
      consequence of lactate binding to membrane receptor(s) or being transported
      through specific carrier-mediated-transporters across the cellular membrane.
      Carriers are distinct in proton-linked-monocarboxylate-transporters (MCTs) and
      Na+-coupled- electrogenic-transporters, expressed by several tissues including
      immune-system, endothelium and epithelium. Several tumors and inflammatory sites
      show accumulation of lactate and altered expression of its transporters, thus
      suggesting a role of this metabolite in cancer and inflammation. We review the
      most recent evidence on lactate biology, focusing on transporter expression and
      function in health and disease. Expert opinion: Lactate-initiated signaling is
      gaining attention for its implications in cancer and inflammation. This review
      discusses the therapeutic potential of targeting lactate transporters and drugs
      that are already in clinical use for cancer and discusses the opportunity to
      develop new therapeutics for inflammation and cancer.

PMID- 30106311
TI  - A randomized trial comparing omega-3 fatty acid plasma levels after ingestion of
      emulsified and non-emulsified cod liver oil formulations.
AB  - OBJECTIVES: Emulsified formulations of omega-3 fatty acids may increase plasma
      concentrations of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)
      compared with non-emulsified formulations. The current study evaluated plasma
      concentrations of DHA + EPA as well as DHA and EPA individually following
      administration of emulsified vs non-emulsified cod liver oil formulations.
      METHODS: In this randomized, 2-period, crossover study (ClinicalTrials.gov
      NCT02428699), 47 healthy adults received single doses of an emulsified cod liver
      oil formulation and a non-emulsified cod liver oil formulation, each containing
      10% cod liver oil plus 10% cod oil and closely matched DHA and EPA content. Blood
      samples were collected for 24 h after dosing to analyze DHA and EPA plasma
      concentrations using a validated methodology. DHA + EPA, DHA, and EPA
      pharmacokinetics were compared using an analysis of covariance model. The
      incremental area under the plasma concentration curve at 24 h (iAUC0-24 h) for
      DHA + EPA was the primary endpoint. RESULTS: DHA + EPA, DHA, and EPA plasma
      concentrations reached higher levels in plasma following administration of the
      emulsified vs non-emulsified formulation. The emulsified cod liver oil
      formulation produced iAUC0-24 h values for DHA + EPA, DHA, and EPA that were
      1.66, 1.78, and 1.64 times higher, respectively, than the non-emulsified
      formulation; iAUC0-10 h values were 1.84, 1.96, and 1.79 times higher,
      respectively (all p < 0.01). Maximum concentrations of DHA + EPA, DHA, and EPA in
      plasma were significantly higher for the emulsified than the non-emulsified
      formulation (p < 0.001). CONCLUSIONS: DHA + EPA, DHA, and EPA plasma
      concentrations were significantly higher for the emulsified cod liver oil
      supplement vs the reference non-emulsified cod liver oil supplement.

PMID- 30106312
TI  - New Approach to Detect Coiled Coil and Leucine Zipper Motifs in Protein
      Sequences.
AB  - This article presents a new approach to detect coiled coil and leucine zipper (L
      Zip) motifs in protein sequences. The approach is based on protein scale
      calculation and sequence analysis. For this purpose, the wavelet-based local
      extrema extraction is employed, and window-based variations of local extrema
      afterward. This, in turn, provided a way to distinguish coiled coil subsequences
      and potential L-Zip motifs. The approach is validated on carefully chosen protein
      sequences that return inconclusive results within known frameworks for L-Zip
      detection, for example, 2ZIP. The results show that this new approach represents
      an improvement over previously presented approaches.

PMID- 30106313
TI  - Short-term rehospitalizations in young adults with schizophrenia treated with
      once-monthly paliperidone palmitate or oral atypical antipsychotics: a
      retrospective analysis.
AB  - OBJECTIVE: To compare rehospitalizations in patients with schizophrenia treated
      with paliperidone palmitate (PP1M) vs oral atypical antipsychotics (OAAs), with a
      focus on young adults (18-35 years). METHODS: The Premier Healthcare database
      (January 2009-December 2016) was used to identify hospitalizations of adults
      (>=18 years) with schizophrenia treated with PP1M or OAA between September 2009
      and October 2016 (index hospitalizations). Rehospitalizations were assessed at
      30, 60, and 90 days after each index hospitalization in young adults and in all
      patients. Proportions of index hospitalizations resulting in rehospitalization
      were reported and compared between groups using odds ratios (ORs) and 95%
      confidence intervals (CIs). RESULTS: A total of 8578 PP1M and 306,252 OAA index
      hospitalizations were included. Hospitalized young adults treated with PP1M (n =
      3791) were more likely to be seen by a psychiatrist (94.0% vs 90.0%), and had a
      longer length of stay (12.5 vs 8.6 days) compared to hospitalized young adults
      treated with OAA (n = 96,502). Following their discharge, young adults receiving
      PP1M during an index hospitalization had a 25-27% lower odds of rehospitalization
      within 30, 60, and 90 days compared to young adults receiving OAAs (all p <
      .001). Similarly, when observing all patients, those receiving PP1M during an
      index hospitalization had 19-22% lower odds of rehospitalization within 30, 60,
      and 90 days compared to those receiving OAAs (all p < .001). CONCLUSIONS:
      Following a hospitalization for schizophrenia, PP1M treatment was associated with
      fewer 90-day rehospitalizations among young adults (18-35 years) relative to OAA
      treatment. This finding was also observed in other hospitalized adults with
      schizophrenia.

PMID- 30106314
TI  - Association of serum ferritin levels with non-alcoholic fatty liver disease in
      postmenopausal women.
AB  - OBJECTIVE: This study aimed to investigate the association between serum ferritin
      levels and the presence of non-alcoholic fatty liver disease (NAFLD) in
      postmenopausal women. METHODS: Two hundred and forty-one postmenopausal women who
      participated in a heath examination program were enrolled in the present study.
      Serum ferritin tertiles were categorized as follows: T1, <=46.4 ng/ml; T2, 46.5
      76.1 ng/ml; and T3, >=76.2 ng/ml. The odds ratios (ORs) and 95% confidence
      intervals (CIs) for NAFLD were calculated after adjusting for confounding
      variables across serum ferritin tertiles using multiple logistic regression
      analysis. RESULTS: The overall prevalence of NAFLD was 41.4% and was
      significantly increased in accordance with the serum ferritin tertiles as
      follows: 30.0% for T1, 40.7% for T2, and 54.3% for T3, respectively. As compared
      with the lowest tertile, the OR (95% CI) for NAFLD in the highest tertile was
      2.69 (1.16-5.28) after adjusting for age, body mass index, regular exercise, mean
      arterial pressure, fasting plasma glucose, triglyceride, high-density lipoprotein
      cholesterol, alanine aminotransferase, and leukocyte count. CONCLUSION: The serum
      ferritin level was positively and independently associated with NAFLD in
      postmenopausal women and could be a useful additional measure in assessing the
      risk of NAFLD in postmenopausal women.

PMID- 30106315
TI  - Development of the medication adherence estimation and differentiation scale
      (MEDS).
AB  - OBJECTIVES: To develop a self-reported measure for medication adherence and
      compare its ability to predict the proportion of days covered (PDC) with
      contemporary scales. METHODS: Retrospective prescription fill data from three
      community pharmacies in the Southeastern US were assessed to identify patients
      that were 18 years of age or older, and had received at least one medication for
      diabetes, hypertension, or dyslipidemia. A cross-sectional survey containing the
      Medication adherence Estimation and Differentiation Scale (MEDS) was administered
      among these pharmacy patrons. The MEDS assessed the extent and reasons for non
      adherence. Survey responses were anonymously linked with retrospective
      prescription fill data. A total of 685 patients were sampled. The proportion of
      days covered (PDC) was used as the criterion measure. The Morisky, Green, and
      Levine Adherence Scale (1986 Morisky scale) and the Medication Adherence Reasons
      Scale (MAR-Scale) were used as comparators. RESULTS: The MEDS presented a five
      factor solution-worries about side-effects, worries about addiction, worries
      about cost, lack of perceived need, and unintentional non-adherence (CFI = 0.97;
      RMSEA = 0.06; SRMR = 0.03; standardized factor loadings greater than 0.5, and
      statistically significant). The relationship between MEDS scores and PDC was
      statistically significant (unstandardized regression coefficient = -0.50, p <
      .01). The MEDS performed better than the 1986 Morisky scale (R2 = 0.02 vs 0.05,
      standardized regression coefficient = -0.13 vs -0.21) and the MAR-Scale (R2 =
      0.02 vs 0.05, standardized regression coefficient = -0.12 vs -0.21) in predicting
      PDC. CONCLUSIONS: The MEDS demonstrated good psychometric properties and
      performed better than the comparator scales in the prediction of PDC.

PMID- 30106316
TI  - ABM Clinical Protocols: An ABM Success Story.

PMID- 30106317
TI  - Comparison of medical and/or surgical management of 23 cats with intracranial
      empyema or abscessation.
AB  - Objectives Feline intracranial abscessation or empyema is infrequently reported
      in the veterinary literature. To date, the largest study is based on a population
      of 19 cats with otogenic infection. The aim of this study was to review a larger
      population of cats with intracranial empyema from multiple aetiologies and
      document their signalment, imaging findings, treatment protocols (including
      medical and/or surgical management) and to compare outcomes. Methods Cases
      presenting to a single referral centre over a 10 year period with compatible
      history, neurological signs and imaging findings consistent with intracranial
      abscessation and empyema were reviewed retrospectively. Results Twenty-three cats
      met the inclusion criteria. Advanced imaging (CT and/or MRI) was performed in
      22/23 cats; one case was diagnosed via ultrasound. Ten cases underwent medical
      and surgical management combined, 10 underwent solely medical management and
      three were euthanased at the time of diagnosis. Short-term outcome showed that
      90% of surgically managed and 80% of medically managed cats were alive at 48 h
      post-diagnosis. Long-term survival showed that surgically managed cases and
      medically managed cases had a median survival time of 730 days (range 1-3802
      days) and 183 days (range 1-1216 days), respectively. No statistical significance
      in short- or long-term survival ( P >0.05) was found between medically and
      surgically managed groups. Conclusions and relevance Feline intracranial
      abscessation and empyema are uncommon conditions that have historically been
      treated with combined surgical and medical management. This study documents that,
      in some cases, intracranial abscessation and empyema can also be successfully
      treated with medical management alone.

PMID- 30106318
TI  - Prediction of Microbe-Disease Associations by Graph Regularized Non-Negative
      Matrix Factorization.
AB  - More and more evidence shows that microbes play crucial roles in human health and
      disease. The exploration of the relationship between microbes and diseases will
      help people to better understand the underlying pathogenesis and have important
      implications for disease diagnosis and prevention. However, the known
      associations between microbes and diseases are very less. We proposed a new
      method called non-negative matrix factorization microbe-disease associations
      (NMFMDA), which used Gaussian interaction profile kernel similarity measure, to
      calculate microbial similarity and disease similarity, and applied a logistic
      function to regulate disease similarity. And, based on the known microbe-disease
      associations, a graph-regularized non-negative matrix factorization model was
      utilized to simultaneously identify potential microbe-disease associations.
      Moreover, fivefold cross-validation was utilized to evaluate the performance of
      our method. It reached the reliable area under receiver operating characteristic
      curve (AUC) of 0.8891, higher than other state-of-the-art methods. Finally, the
      case studies on three complex human diseases (i.e., asthma, inflammatory bowel
      disease, and colon cancer) demonstrated the good performance of our method. In
      summary, our method can be considered as an effective computational model for
      predicting potential disease-microbe associations.

PMID- 30106319
TI  - A comparative study of intratracheal and aerosolization instillations of
      bleomycin inducing experimental lung fibrosis in rat.
AB  - We aimed to investigate in the present work, using metabonomics approaches, the
      scalability of lung fibrosis-biomarkers, in bleomycin (BLM) model of pulmonary
      fibrosis in rats. Sixty male Wistar rats, weighing 250 +/- 10 g, were randomly
      divided into three groups: a negative control group receiving normal saline
      treatment (G1), an intratracheal BLM instilled group (G2), and an aerosol BLM
      instilled group (G3). Rats were investigated at various times after BLM
      instillation. Metabolic changes observed in different biofluids have been
      integrated into the results of the histological examination (increase in
      inflammation, fibrosis score, and TGF-beta immunostaining) which provide a novel
      pathway of biomarkers in pulmonary fibrosis. These two BLM-models showed an
      efficacy in the production of pulmonary fibrosis in rats, accompanied by an
      oxidative stress in lung tissue as assessed by the increase of lipid peroxidation
      and the depletion in the level of antioxidant enzymes such as superoxide
      dismutase and catalase. The aerosol model was more advantageous showing fibrotic
      foci occupying the majority of the lung in contrast to intratracheal instillation
      characterized by a non-homogeneous distribution of the fibroblastic foci.

PMID- 30106320
TI  - Heart sparing breast cancer radiotherapy using continuous positive airway
      pressure (CPAP) and conventional supine tangential fields: an alternative method
      for patients with limited accessibility to advanced radiotherapy techniques.

PMID- 30106321
TI  - Potentially Inappropriate Prescribing in Australian Nursing Home Residents with
      Advanced Dementia: A Substudy of the IDEAL Study.
AB  - BACKGROUND: Prescribing medications for nursing home residents with advanced
      dementia should focus on optimizing function and comfort, reducing unnecessary
      harms and aligning care goals with a palliative approach. OBJECTIVE: The aim of
      the study was to estimate the proportion of Australian nursing home residents
      with advanced dementia receiving potentially inappropriate medications, and
      identify those most commonly prescribed and factors associated with their use.
      DESIGN: Data were collected through retrospective audit of medication charts.
      SETTING/SUBJECTS: Two hundred eighteen nursing home residents with advanced
      dementia from 20 nursing homes participated in a cluster-randomized controlled
      trial of case conferencing (the IDEAL Study) from June 2013 to December 2014.
      MEASUREMENTS: Inappropriate drug use was defined as medications classified as
      "never appropriate" by the Palliative Excellence in Alzheimer Care Efforts
      (PEACE) program criteria. Generalized linear mixed models were used to identify
      variables predicting use of "never" appropriate medications. RESULTS: Over a
      quarter (n = 65, 30%) of residents received at least one medication classed as
      "never" appropriate, the most common being lipid-lowering agents (n = 38, 17.4%),
      antiplatelet agents (n = 18, 8.3%), and acetylcholinesterase inhibitors (n = 16,
      7.3%). Residents who had been at the nursing home for <=10 months (odds ratio
      [OR] 5.60, 95% confidence interval [CI] 1.74-18.06) and 11-21 months (OR 5.41,
      95% CI 1.67-17.75) had significantly greater odds of receiving a never
      appropriate medication compared with residents who had been at the nursing home
      for >5 years. CONCLUSIONS: Use of potentially inappropriate medications in
      Australian nursing home residents with advanced dementia is common. A greater
      understanding of the rationale that underpins prescribing of medications is
      required.

PMID- 30106323
TI  - Naringenin palliates cisplatin and doxorubicin gonadal toxicity in male rats.
AB  - Cisplatin (CP) and doxorubicin (DX) can cause testicular injury by inducing
      oxidative/nitrosative stress, inflammation, and apoptosis, Naringenin (NG) has
      antioxidant, antinitrative, anti-inflammatory, and anti-apoptotic effects. This
      study investigated the potential ability of NG to block gonadotoxicity induced CP
      and DX in male rats. The rats received one injection of either CP (10 mg/kg,
      i.p.) or DX (15 mg/kg, i.p.), and treated with NG (50 mg/kg/day, p.o.) for 10
      days beginning 6 days prior to CP and DX administration. NG significantly
      prevented the decreases of serum testosterone and inhibin B in rats received CP
      and DX. Additionally, NG significantly decreased the elevated testicular
      malondialdehyde, tumor necrosis factor-alpha/interleukin-10 ratio, and caspase-3
      in CP- and DX-treated rats. NG also significantly raised the decreased testicular
      Bcl-2/Bax ratio, and total antioxidant status in CP- and DX-challenged rats. In
      addition, NG significantly increased P-glycoprotein level in testes of rats
      received CP and DX. Moreover, NG significantly decreased the testicular
      histopathological injury, and immunohistochemical expression of inducible nitric
      oxide synthase induced by CP and DX in rat testes. It was concluded that NG
      impeded gonadotoxicity of CP and DX in male rats by mitigating oxidative stress,
      nitrosative stress, inflammation, and apoptosis.

PMID- 30106322
TI  - PTEN-L puts a brake on mitophagy.
AB  - : Mitophagy is a main type of selective autophagy, via which damaged mitochondria
      are selectively degraded via the autophagic pathway. The protein kinase PINK1 and
      E3 ubiquitin ligase PRKN are the most well studied regulators of mitophagy, via a
      feedforward mechanism involving ubiquitin phosphorylation (p-Ser65-Ub) and
      accumulation at the damaged mitochondria. However, it is unknown whether there is
      a protein phosphatase against PINK1-mediated phosphorylation of ubiquitin. We
      recently reported that PTEN-L, a newly identified PTEN isoform, is a novel
      negative regulator of mitophagy through dephosphorylation of p-Ser65-Ub. Our data
      demonstrate that a significant portion of PTEN-L localizes at the outer
      mitochondrial membrane and is able to prevent PRKN's mitochondrial translocation,
      reduce the phosphorylation of PRKN, impair its E3 ligase activity as well as
      maintain PRKN in a closed/inactive status. Moreover, we found that PTEN-L
      dephosphorylates p-Ser65-Ub to disrupt the feedforward mechanism of mitophagy.
      Our findings suggest that PTEN-L acts as a brake in the regulation of mitophagy.
      ABBREVIATIONS: ATR: alternatively translated region; CCCP: carbonylcyanide 3
      chlorophenylhydrazone; DUBs: deubiquitinating enzymes; MFN2: mitofusion2; MS/MS:
      tandem mass spectrometry; mtDNA: mitochondrial DNA; MTS: mitochondrial targeting
      sequences; O/A: oligomycin and antimycin A; PINK1: PTEN induced putative kinase
      1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; PTEN: phosphatase and
      tensin homolog; PTEN-L: phosphatase and tensin homolog-long; Ub: ubiquitin; USP:
      ubiquitin-specific proteases; YFP: yellow fluorescence protein.

PMID- 30106324
TI  - miRNAs in enterovirus infection.
AB  - During the last years, it has become evident that miRNAs are important players in
      almost all physiological and pathological processes, including viral infections.
      Enterovirus infections range from mild to severe acute infections concerning
      several organ systems and are also associated with chronic diseases. In this
      review, we summarize the findings on the impact of acute and persistent
      enterovirus infection on the expression of cellular miRNAs. Furthermore, the
      currently available data on the regulation of cellular or viral targets by the
      dysregulated miRNAs are reviewed. Finally, a translational perspective, namely
      the use of miRNAs as biomarkers of enterovirus infection and as antiviral
      strategy is discussed.

PMID- 30106325
TI  - Imatinib mesylate in the management of chemotherapy-induced pulmonary toxicity: a
      double-edged sword.

PMID- 30106327
TI  - Solubility enhancement and solid-state characterisation.

PMID- 30106326
TI  - Microvascular complications of diabetes worsen long-term functional outcomes
      after acute ischemic stroke.
AB  - Objective This study was performed to evaluate the potential predictors of poor
      outcomes associated with diabetes-specific microvascular pathologies and to
      analyze their influence on clinical outcomes by adjusting for other well-known
      prognostic factors in patients with acute ischemic stroke. Methods We analyzed
      1389 consecutive adult patients with acute ischemic stroke and explored the
      relationship among clinical characteristics, laboratory measurements, imaging
      findings, and 6-month functional outcomes. Results The final study population
      comprised 216 patients with both acute ischemic stroke and diabetes mellitus who
      were followed up for 6 months. A multiple logistic regression analysis of poor
      outcomes revealed the following independent predictors: leukoaraiosis severity
      [odds ratio (OR), 7.38; 95% confidence interval (CI), 1.40-38.86, per 1-point
      increase), diabetic nephropathy (OR, 10.66; 95% CI, 1.10-103.43), and the
      admission National Institutes of Health stroke scale score (OR, 2.58; 95% CI,
      1.36-4.92 per 1-point increase). In this model, admission hyperglycemia and
      intracerebral hemorrhagic transformation were not independent prognostic
      predictors. Conclusion Microvascular complications (such as nephropathy) caused
      by diabetes mellitus predict an unfavorable clinical outcome after acute ischemic
      stroke. Diabetic nephropathy may partly affect post-stroke prognosis by means of
      exacerbating leukoaraiosis.

PMID- 30106328
TI  - Effects and mechanisms of differently cued and non-cued motor imagery in people
      with multiple sclerosis: A randomised controlled trial.
AB  - BACKGROUND: Walking impairment and fatigue are prevalent symptoms in people with
      multiple sclerosis (PwMS). Motor imagery (MI) with rhythmic auditory cueing
      improved walking in PwMS, but so far, the underlying mechanisms are not fully
      explored. OBJECTIVE: This study investigated the effects and mechanisms of
      differently cued and non-cued MI on walking, fatigue and quality of life (QoL) in
      PwMS. METHODS: A total of 60 PwMS with mild to moderate disability were
      randomised to music- and verbally cued MI (MVMI), music-cued MI (MMI) or MI.
      Participants practised cued or non-cued MI of walking for 17 minutes, six times
      per week for 4 weeks at home. Primary outcomes were walking speed (timed 25-foot
      walk) and walking distance (6-minute walk test). RESULTS: A total of 59
      participants completed the study. All interventions induced significant
      improvements in walking speed and distance, while MVMI was superior. After cued
      MI, fatigue and QoL significantly improved, with greatest changes seen after
      MVMI. All participants showed high MI ability. Post-intervention, sensorimotor
      synchronisation (SMS) was significantly more accurate after cued MI. CONCLUSION:
      All interventions significantly improved walking. MVMI was superior in improving
      walking, fatigue and QoL. Results suggest that MI and SMS were mechanisms of
      action.

PMID- 30106329
TI  - Effect of Active Application on Bond Durability of Universal Adhesives.
AB  - The purpose of this study was to determine the effect of different adhesive
      application methods and etching modes on the dentin bond durability of universal
      adhesives under thermal cycling (TC). All-Bond Universal (Bisco), Adhese
      Universal (Ivoclar Vivadent), and Scotchbond Universal (3M ESPE) were used as
      adhesives. In total, 600 bovine teeth with exposed dentin were divided into 12
      groups according to the type of adhesive and subjected to the following bonding
      procedures: 1) etch-and-rinse mode with active application; 2) etch-and-rinse
      mode with inactive application; 3) self-etch mode with active application; and 4)
      self-etch mode with inactive application. Bonded specimens were stored in
      distilled water at 37 degrees C for 24 hours and then subjected to 5000, 10,000,
      30,000, or 50,000 TC between 5 degrees C and 55 degrees C before shear bond
      strength (SBS) testing, creating a division into a total of five different
      storage conditions. Baseline specimens were stored in distilled water at 37
      degrees C for 24 hours. The SBS test was performed at a cross-head speed of 1.0
      mm/min. Three-way analysis of variance revealed that all the factors of
      application mode, adhesive, and thermal cycle period significantly influenced the
      SBS values ( p<0.001), regardless of the etching mode. In the baseline groups,
      all of the tested adhesives with active application had higher SBS values than
      those with inactive application, regardless of etching mode. In the TC groups,
      significantly lower SBS values were observed at 50,000 TC with inactive
      application compared to those with active application, regardless of the etching
      mode. From the scanning electron microscopy observation of demineralized and
      deproteinized resin/dentin interfaces, dense resin tags longer than 50 MUm were
      observed in the etch-and-rinse with active application group. On the other hand,
      the resin tags in self-etch mode were sparse, thin, and much shorter than those
      in etch-and-rinse mode. Comparing the penetration status of the resin tags with
      active and inactive application in self-etch mode, the resin tag penetration with
      inactive application was much lower than that with active application. Active
      application is effective in enhancing the dentin bond durability of universal
      adhesives. When using universal adhesives with different etching modes,
      practitioners should select the optimal etching mode and appropriate application
      method in accordance with the cavity conditions.

PMID- 30106330
TI  - Impact of Silane-containing Universal Adhesive on the Biaxial Flexural Strength
      of a Resin Cement/Glass-Ceramic System.
AB  - The aim of this study was to determine whether using a silane-containing
      universal adhesive as a silane primer in glass-ceramic/resin cement systems
      affects biaxial flexural strength (BFS) and bonded interface integrity after
      loading. Glass-ceramic (IPS e.max CAD, Ivoclar/Vivadent, Schaan, Liechtenstein)
      disc-shaped specimens (6.5+/-0.1mm in diameter, 0.5+/-0.1mm thick) were etched
      with 5% hydrofluoric acid (HF) for 20 seconds and divided into four groups of 30
      specimens, to be treated as follows: 1) One bottle silane primer (RCP); 2)
      Separate application of silane and adhesive (RCP+SB); 3) Silane-containing
      universal adhesive (SBU); 4) No treatment (C). After silanization, all specimens
      were resin cement- coated and polymerized for 40 seconds. Each specimen layer was
      measured, as well as each assembly's thickness, using a digital caliper and
      scanning electron microscope (SEM). Specimens were stored for 24 hours and
      submitted to a BFS test (1.27 mm/min). BFS values were calculated using the
      bilayer disc-specimen solution. Bonded interfaces were analyzed on fractured
      fragments using SEM. One-way ANOVA and Tukey tests (alpha=0.05) were applied, as
      well as the Weibull analysis. Factor "silane treatment" was statistically
      significant ( p<0.0001). RCP+SB (372.2+/-29.4 MPa) and RCP (364.2+/-29.5 MPa)
      produced significantly higher BFS than did the C (320.7+/-36.3 MPa) or SBU
      (338.0+/-27.1 MPa) groups. No differences were found in the Weibull modulus ( m:
      RCP: 10.1-17.3; RCP+SB: 10.1-17.0; SBU: 12.3-22.4; C: 7.4-12.9). Bonded interface
      analysis exhibited ceramic-cement separation (SBU, C) and voids within the resin
      cement layer (all groups). Neither the ceramic/cement system's BFS nor its bonded
      interface stability were improved by SBU after loading.

PMID- 30106331
TI  - Seven-year Follow-up of Resin Infiltration Treatment on Noncavitated Proximal
      Caries.
AB  - The purpose of this case report is to present success and failure outcomes of
      seven-year follow-up of resin infiltration treatment (RIT) used for the proximal
      caries of maxillary premolars. Although resin infiltration can be a good option
      for micro-invasive treatment, long-term follow-up data are not sufficient, and
      the outcome of this technique can be affected by factors such as technique
      sensitivity of procedure, patient's caries risk, and depth of caries progression.
      Therefore, careful case selection, application, and follow-up are needed.

PMID- 30106332
TI  - Does a Self-Etching Ceramic Primer Improve Bonding to Lithium Disilicate
      Ceramics? Bond Strengths and FESEM Analyses.
AB  - OBJECTIVE: To compare the effect of hydrofluoric acid (HF) vs self-etching
      ceramic primer on resin cement microshear bond strength (MUSBS) and
      ultramorphology of lithium disilicate (LD) ceramic. METHODS AND MATERIALS: LD
      (IPS e.max CAD, Ivoclar Vivadent) blocks (14*4*2 mm3) were polished to 1200 grit
      and assigned to nine groups (n=5): CON: control, no LD surface treatment; IVO:
      5.0% HF (IPS Ceramic Etching Gel, Ivoclar Vivadent); VIT: 5.0% HF (Vita Ceramics
      Etch, VITA Zahnfabrik); FGM: 5.0% HF (Condac Porcelana, FGM); ULT: 9.0% HF
      (Porcelain Etch, Ultradent); PRM: 9.6% HF (Premier Porcelain Etch Gel, Premier);
      BIS: 9.5% HF (Porcelain Etchant, Bisco Inc); DEN: 10.0% HF (Condicionador de
      Porcelanas, Dentsply Brazil); and MEP: self-etching ceramic primer (Monobond Etch
      & Prime, Ivoclar Vivadent). For all HF groups and control, an MDP-containing
      silane solution (MB+, Monobond Plus, Ivoclar Vivadent) was applied on rinsing the
      HF gel and air drying. Three transparent matrices for each specimen were filled
      with light-cured resin cement (Variolink Veneer, Ivoclar Vivadent). After storage
      in water for 48 hours at 37 degrees C, specimens were tested in shear mode to
      measure MUSBS. Mode of failure was analyzed at 50*. Statistical analysis included
      one-way analysis of variance and the Duncan post hoc test (alpha=0.05). Thirty
      six additional LD specimens were assigned to the same experimental groups (n=4)
      and observed under a field-emission scanning electron microscope (FESEM) at
      magnifications ranging from 10,000* to 100,000*. RESULTS: IVO resulted in
      statistically higher mean MUSBS than all the other groups. MEP resulted in
      statistically lower MUSBS than all HF groups. The failure mode for MEP was
      predominantly adhesive. The most frequent failure mode for the HF groups was
      mixed. CON resulted in 100% pretesting failures. For FESEM, no retentive pattern
      was observed for CON specimens. MEP resulted in the least pronounced etching
      pattern, few areas around crystals exhibited a slight increase in retention
      pattern compared to the control group. All HF gels created microporosities on the
      LD surface with distinct etching patterns. VIT and DEN resulted in an LD
      ultramorphology that suggested overetching. CONCLUSIONS: HF etching followed by a
      silane solution resulted in higher bond strengths than a self-etching ceramic
      primer. Some HF gels may cause overetching of the LD intaglio surface.

PMID- 30106333
TI  - Effect of Calcium-phosphate Desensitizers on Staining Susceptibility of Acid
      eroded Enamel.
AB  - OBJECTIVE: To investigate the effect of calcium-phosphate-based desensitizers,
      Teethmate AP paste (TMAP) and Teethmate Desensitizer (TMD) (Kuraray Noritake
      Dental, Tokyo, Japan), on the prevention of staining on acid-eroded enamel.
      METHODS AND MATERIALS: Forty polished enamel samples (4*4*1 mm) from bovine
      incisors were randomly divided into five groups (n=8). After immersion in 50 mL
      of 0.5% citric acid (pH 2.5) for 15 minutes to form acid-eroded surfaces, the
      surfaces were subjected to different treatments with TMAP, TMD, and NaF (0.21%
      means 950 ppm) for five minutes. Another eroded group was not treated with
      desensitizer. For the control group, the samples were not eroded or treated. All
      the samples were stored in artificial saliva (AS) at pH 7.2 for 24 hours at 37
      degrees C. The TMAP, TMD, or NaF was reapplied at eight and 16 hours during the
      24 hours of storage time. The surface roughness (Sa) was evaluated following ISO
      25178 for surface texture using confocal laser scanning microscopy (VK-X 150
      series, Keyence, Osaka, Japan) before acid erosion, after acid erosion, and after
      24 hours of incubation in AS. Afterward, the color difference was measured with a
      dental colorimeter (Shade Eye NCC, Shofu, Kyoto, Japan) before and after staining
      with tea solution. RESULTS: One-way repeated measures analysis of variance showed
      that acid erosion significantly increased Sa ( p<0.001). TMAP- and TMD-treated
      groups exhibited lower Sa values than the NaF group and the no-desensitizer
      treatment group. The greatest staining was observed in the NaF group and the no
      desensitizer group, while the TMAP and TMD groups significantly decreased the
      formation of stains. CONCLUSIONS: Acid-eroded enamel increased surface roughness
      and tended to absorb more stains. However, the application of TMAP and TMD
      moderated the roughness and thus prevented the formation of extrinsic stains.

PMID- 30106334
TI  - Effect of Irradiance and Exposure Duration on Temperature and Degree of
      Conversion of Dual-Cure Resin Cement for Ceramic Restorations.
AB  - This study investigated the effects of irradiance and exposure duration on dual
      cured resin cements irradiated through ceramic restorative materials. A single
      light-curing unit was calibrated to three different irradiances (500, 1000, and
      1500 mW/cm2) and irradiated to three different attenuating materials (transparent
      acryl, lithium disilicate, zirconia) with 1-mm thicknesses for 20 or 60 seconds.
      The changes in irradiance and temperature were measured with a radiometer (or
      digital thermometer) under the attenuating materials. The degree of conversion
      (DC) of dual-cure resin cement after irradiation at different irradiances and
      exposure durations was measured with Fourier transform near infrared
      spectroscopy. Two-way analysis of variance revealed that irradiance ( p<0.001)
      and exposure duration ( p<0.001) significantly affected temperature and DC. All
      groups showed higher DCs with increased exposure times ( p<0.05), but there were
      no statistically significant differences between the groups irradiated with 1000
      mW/cm2 and 1500 mW/cm2 ( p>0.05). Higher-intensity irradiances yielded higher
      temperatures ( p<0.05), but exposure time did not affect temperature when
      materials were irradiated at 500 mW/cm2 ( p>0.05).

PMID- 30106335
TI  - Comparison of Whitening Dentifrices on the Effectiveness of In-Office Tooth
      Bleaching: A Double-Blind Randomized Controlled Clinical Trial.
AB  - OBJECTIVES: To investigate the effect of whitening dentifrices on the
      effectiveness of in-office tooth bleaching. METHODS AND MATERIALS: A double-blind
      randomized controlled clinical trial was performed. The participants were
      randomly allocated into three groups according to the different dentifrices used
      during this clinical trial: regular dentifrice (group C), conventional whitening
      dentifrice (group CW), and whitening dentifrice containing blue covarine (group
      CU). All participants received in-office tooth bleaching for the maxillary
      anterior teeth (two sessions conducted at a one-week interval). Tooth color was
      measured with a spectrophotometer at baseline (T1), after the first bleaching
      session (T2), after the second bleaching session (T3); one week after the
      completion of in-office bleaching (T4); and three weeks after the completion of
      in-office bleaching (T5). The data were statistically analyzed through repeated
      analysis of variance and the Tukey test (alpha=0.05). RESULTS: Sixty participants
      completed the study (n=20 per group). At T3, group CU exhibited the lowest DeltaE
      values ( p=0.008). The DeltaE values increased from T4 to T5 in the CW and CU
      groups, whereas a decrease in DeltaE values was observed for group C.
      CONCLUSIONS: The use of a whitening dentifrice containing blue covarine during in
      office bleaching reduced color changes. After tooth bleaching, brighter tooth
      colors were observed in the participants who brushed with whitening dentifrices
      compared to those who brushed with a regular dentifrice.

PMID- 30106336
TI  - Statistical approach to identify food categories that determine daily intake
      levels of total and inorganic arsenic, lead and aluminium of Japanese diet.
AB  - Food categories that significantly contribute to daily intake of total arsenic
      (TAs), inorganic arsenic (iAs), lead (Pb) and aluminium (Al) were statistically
      sought for the 949 duplicate diet samples collected from 319 households in Japan.
      Daily intakes of TAs, iAs, Pb and Al were calculated based on measured element
      concentration in duplicate diet samples and weight of the samples. Amounts of
      consumption of 12 food categories of each duplicate diet sample were self
      reported (beverage), interviewed (fat and oil, spices, and sugar) and actually
      weighted (other 9 categories) at the time of diet sampling. Multiple regression
      analyses were conducted by using daily element intake as dependent variable and
      amounts of daily consumption of the 12 food categories as independent variables.
      The most significant predictors were amount of daily consumption of 'Fish &
      Shellfish' for daily TAs intake and 'Rice & Rice products' for iAs intake. Other
      food categories contributed to daily intakes of the four elements with smaller
      coefficient. Some of the significant predictors identified in this study were
      consistent with the findings of the previous market basket surveys while others
      were not. The 12 food category consumption data moderately explained daily intake
      of TAs (Coefficient of determination adjusted for degree of freedom (adjusted R2)
      = 0.447) and iAs (0.307) while they only poorly explained daily intakes of Pb
      (0.229) and Al (0.117). The present results suggest that a Total Diet Study based
      on food consumption survey data and element contents of food from data
      base/literature will result in large errors in the estimation of daily element
      intake.

PMID- 30106337
TI  - MOLECULAR CHARACTERIZATION OF THEILERIA SPP. IN GOATS FROM SHAANXI PROVINCE,
      NORTHWESTERN CHINA.
AB  - Theileriosis is an important tick-borne pathogen of livestock globally, causing
      severe reduction of livestock productivity and economic loss. To systematically
      investigate the prevalence and species of Theileria spp. in goats from Shaanxi
      province, a total of 509 blood samples were collected from dairy, cashmere and
      meat goats from 7 counties, and examined by using the microscopic examination and
      the nested PCR targeting the SSU rRNA gene. Of them, 268 (52.7%, 268/509) were
      positive for Theileria infection. The prevalence was closely associated with ages
      and production categories. The highest infection was found in meat goats of 7 to
      12-months, and lowest was detected in cashmere goats of 3 to 6 months. Sequence
      analysis indicated the presence of 2 Theileria species, with Theileria luwenshuni
      as the prevalent species and the first report of Theileria sp. OT3 in goats in
      China. These findings indicated the wide distribution of Theileria spp. in goats
      of Shaanxi province, and would shed new light on the distribution of this
      parasite in China.

PMID- 30106338
TI  - Translabial US Assessment of Midurethral Slings: Providing Clarity on a Stressful
      Situation.

PMID- 30106339
TI  - Multiclass screening in urine by comprehensive two-dimensional liquid
      chromatography time of flight mass spectrometry for residues of sulphonamides,
      beta-agonists and steroids.
AB  - Nowadays routine residue monitoring involves the analysis of many compounds from
      different classes, mainly in urine. In the past two decades, developments heavily
      focused on the use of mass spectrometers (MS) and faster and more sensitive MS
      detectors have reached the market. However, chromatographic separation (CS) was
      rather ignored and the cognate developments in CS were not in line. As a result,
      residue analysis did not improve to the extent anticipated. CS by LC x LC is a
      promising technique and will enable a further increase in the range of compounds
      and compound classes that can be detected in a single run. In the present study,
      a self-built LC x LC system, using a 10 port valve, was connected to a single
      quadrupole MS with electrospray interface. Standards containing a mixture of
      sulphonamides, beta-agonists and (steroid) hormones, 53 compounds, in total, were
      analysed. Results demonstrated that these compounds were well separated and could
      be detected at low levels in urine, i.e. limit of detection (LOD) from 1 ug L-1
      for most beta-agonists to 10 ug L-1 for some sulphonamides and most hormones. To
      enhance the sensitivity, optimisation was performed on an advanced commercial LC
      x LC system connected to a full scan accurate MS. This ultimately resulted in a
      fast high throughput untargeted method, including a simple sample clean-up in a
      96-well format, for the analysis of urine samples.

PMID- 30106340
TI  - To Hold or Not to Hold Metformin for FDG PET Scans: That Is the Question.

PMID- 30106341
TI  - Acoustic Radiation Force Impulse Elastography: Tissue Stiffness Measurement in
      Limb Lymphedema.
AB  - Purpose To evaluate the feasibility of cutaneous and subcutaneous limb tissue
      elasticity measurement in participants with limb lymphedema by using acoustic
      radiation force impulse (ARFI) elastography. Materials and Methods From July 2015
      to June 2017, ARFI elastography was performed in 64 participants with lymphedema
      (seven men and 57 women; age range, 23-85 years) by using a US system. Tissue
      stiffness quantification with shear-wave velocity (SWV) was obtained in the
      cutaneous and subcutaneous limb tissues. Lymphoscintigraphy was the reference
      standard. Results SWV was significantly higher in limbs with lymphatic
      obstruction than in unaffected limbs (cutaneous tissue: 2.75 m/sec vs 1.74 m/sec,
      respectively; subcutaneous tissue: 1.90 m/sec vs 1.35 m/sec, respectively; P <
      .001). SWV was significantly different among limbs without lymphatic drainage
      obstruction, with partial obstruction, and with total obstruction (cutaneous
      tissue: 1.74 m/sec vs 2.75 m/sec vs 2.77 m/sec; subcutaneous tissue: 1.35 m/sec
      vs 1.90 m/sec vs 1.90 m/sec, respectively; P < .001). By using a cut-off value of
      2.10 m/sec and 1.43 m/sec for cutaneous and subcutaneous tissue, respectively,
      sensitivity was 83.1% (59 of 71) and 80.3% (57 of 71), and specificity was 86.0%
      (49 of 57) and 70.2% (40 of 57) for manifestation of lymphatic obstruction. The
      corresponding areas under the receiver operating characteristic curve were 0.91
      and 0.83, respectively. Conclusion Acoustic radiation force impulse elastography
      showed that cutaneous and subcutaneous tissues are stiffer in lymphedematous
      limbs than in unaffected limbs. Acoustic radiation force impulse elastography is
      a feasible imaging modality for noninvasive tissue stiffness quantification in
      limb lymphedema. (c) RSNA, 2018 Online supplemental material is available for
      this article.

PMID- 30106342
TI  - Can CT Following Chemoembolization with Radiopaque Drug-Eluting Beads Tell Us How
      Much Drug We Deliver?

PMID- 30106343
TI  - Target Size Variation in Microdosimetric Distributions and its Impact on the
      Linear-Quadratic Parameterization of Cell Survival.
AB  - The linear-quadratic (LQ) parameterization of survival fraction [SF( D)]
      inherently assumes that all cells in a population receive the same dose ( D),
      albeit the distribution of specific energy z over the individual cells f( z, D)
      can be very wide. From these microdosimetric distributions, which are target size
      dependent, we estimate the size of the cellular sensitive volume by analyzing its
      influence on the LQ parameterization of cell survival. A Monte Carlo track
      structure code was used to simulate detailed tracks from a 60Co source as well as
      proton and carbon ions of various energies. From these tracks, f( z, D)
      distributions were calculated for spherical targets with diameters ranging from
      10 nm to 12 MUm. A cell survival function based on f( z, D) was fitted to
      experimental LQ alpha values, revealing an intrinsic limitation that target size
      imposes on the usage of f( z, D) to describe the linear term of the LQ
      parameterization. The results indicate that such threshold volume arises
      naturally from the relationship between the particle's probability of no-hit and
      the probability of cell survival. Further analysis led to the proposal of a
      radiobiological property [Formula: see text], defined as the mean lineal energy
      corresponding to the target size that allows equivalence between the mean
      inactivation dose (MID) and the mean specific energy [Formula: see text]. The
      fact that [Formula: see text] is an increasing continuous function of target size
      within the range of biological targets of interest in radiobiology, ensures the
      uniqueness of [Formula: see text] for any radiation quality, thus, its potential
      usefulness in modeling. In conclusion, an accurate estimation of such threshold
      volumes may be useful for improving modeling of cell survival curves.

PMID- 30106344
TI  - The role of peripheral vision in vertical road sign identification and
      discrimination.
AB  - The role of peripheral vision in road sign identification and discrimination was
      investigated in two studies. Peripheral vision plays an important role in road
      signs perception due to their lateral positioning. In the first study 20
      participants identified road signs presented at five levels of horizontal
      eccentricity (1.1 degrees -12.4 degrees ), and two levels of vertical
      eccentricity (0 degrees -2.5 degrees ). In the second study road sign
      discrimination was tested in a same-different discrimination task. The first
      study showed that a vertical offset of 2.5 degrees  degraded proportion correct
      rate by 9%. Proportion correct rate decreased from 79% to 41% in the transition
      from 1.1 degrees  to 12.4 degrees  of horizontal offset. The second study showed
      an accurate discrimination for road signs presented within a horizontal offset of
      6.4 degrees . Road signs with angular shapes and prominent vertexes as triangular
      or cross signs were better identified in peripheral vision than signs with more
      compact shapes (circular signs). Practitioner summary: Vertical road signs, due
      to their lateral positioning, are often perceived in peripheral vision.
      Horizontal and vertical eccentricity negatively impacts the driver's ability to
      correctly identify and discriminate traffic signs. The use of singular shapes and
      a design with simple pictograms and large contrasting areas strongly facilitate
      road sign perception in peripheral vision.

PMID- 30106345
TI  - Activated carbon added to recycled paperboard to prevent migration into food:
      approach for determining efficacy, and first results.
AB  - Catcherboard MB12(r) from Smurfit Kappa is a recycled paperboard incorporating
      activated carbon to reduce the release of contaminants into food. An approach is
      proposed to determine the efficacy of the activated carbon. Sorption into
      activated carbon increases the concentration ratio paperboard/food (distribution
      coefficient) and reduces the migration rate, i.e. prolongs the time for
      equilibration. Using silicone paper as food simulant, the concentration ratio was
      increased by a factor of at least 1000 compared to recycled paperboard without
      activated carbon, which is sufficient to meet the 1% criterion proposed for
      barriers. Sorbents have limited capacity. A load with in total 4000 mg surrogate
      substances/kg paperboard (in addition to the material from the paperboard)
      exceeded the capacity: concentration ratios were reduced and the release of
      paperboard constituents increased. Capacity is consumed by constituents from the
      printing inks and the packed food. Total amounts of substances in dry foods of
      sufficient volatility to potentially migrate into the paperboard through the gas
      phase at ambient temperature were determined by GC-FID. For the large majority of
      the dry foods, these amounts were clearly below the capacity limit even under the
      exaggerated assumption of total transfer. Migration of mineral oil hydrocarbons
      into cat food over up to 1 year was not detectable at 1 mg/kg. It is concluded
      that recycled paperboard with activated carbon is promising for respecting the 1%
      criterion stipulated for functional barriers to avoid food contamination from
      recycled paperboard.

PMID- 30106346
TI  - Translabial US: Preoperative Detection of Midurethral Sling Erosion in Stress
      Urinary Incontinence.
AB  - Purpose To evaluate the performance of translabial (TL) US in preoperative
      detection of sling erosion into pelvic organs with cystourethroscopic and
      surgical correlation. Materials and Methods The study cohort included women who
      underwent surgery at a subspecialty center (from 2008 to 2016) for suspected mesh
      complications in the setting of previous midurethral sling placement for stress
      urinary incontinence (from 1999 to 2012) with available preoperative TL US
      imaging. Clinical information, the finding of sling erosion identified
      intraoperatively and at cystourethroscopy, and blinded dual-reader radiologic
      analysis of the TL US studies for mesh location (intraluminal, mural, or
      extramural) relative to pelvic organs (bladder, urethra, vagina, or rectum) were
      evaluated. The diagnostic performance of TL US was correlated with the reference
      standard of surgical findings. The consensus of two radiologists was recorded,
      and interobserver agreement was evaluated with the kappa statistic. Results Of
      the 124 women who were suspected of having sling erosion (mean age, 57.5 years +/
      11.1 [standard deviation]), 15 women (12.1%) had sling erosion into the urethra
      or bladder at surgery. Sensitivity and specificity for erosion at TL US were 53%
      (95% confidence interval: 45%, 62%) and 100% (95% confidence interval: 97%,
      100%), respectively, when erosion was defined as only intraluminal mesh products.
      Sensitivity and specificity for erosion at TL US were 93% (95% confidence
      interval: 89%, 98%) and 72% (95% confidence interval: 65%, 80%), respectively,
      when erosion was defined as visualizing either intraluminal or intramural mesh
      products. Interobserver agreement (kappa value) was 0.95. Cystourethroscopy had
      67% sensitivity and 100% specificity for sling erosion. Conclusion Preoperative
      translabial US can be used to detect sling erosion into the lower urinary tract,
      with sensitivity up to 93% and specificity up to 100%. (c) RSNA, 2018 Online
      supplemental material is available for this article. See also the editorial by
      Benson and Phillips in this issue.

PMID- 30106348
TI  - Metformin Discontinuation prior to FDG PET/CT: A Randomized Controlled Study to
      Compare 24- and 48-hour Bowel Activity.
AB  - Purpose To investigate the relationship of 24- and 48-hour metformin
      discontinuation to bowel uptake of fluorine 18 fluorodeoxyglucose (FDG) on PET/CT
      scans. Materials and Methods Patients with diabetes who were treated with
      metformin and referred for FDG PET/CT were randomized to three equal groups based
      on duration of metformin discontinuation: 24 hours, 48 hours, and no
      discontinuation (control group). Two interpreters blinded to the study groups
      assessed FDG uptake in multiple segments of small and large bowel qualitatively
      and semiquantitatively by using maximum standardized uptake values (SUVsmax).
      Differences in age, sex, weight, dose of metformin, duration of metformin
      treatment, blood glucose levels, and FDG dose injected were assessed. Data were
      analyzed with analysis of variance when passing normality, and by nonparametric
      testing when not. Results Ninety study participants (62 male, 28 female; median
      age, 70 years) were enrolled from July 2010 through March 2012. There were no
      differences between study groups in weight, blood glucose levels 3 days prior to
      scanning, or normal organ uptake. Large bowel SUVmax was lower after 24 hours
      (4.10 +/- 2.00 vs 5.42 +/- 2.36; P = .020) and 48 hours (2.63 +/- 0.88 vs 5.42 +/
      2.36; P ? .001) of metformin discontinuation than for no discontinuation
      (control), and for 48 hours versus 24 hours of discontinuation (P = .0015). Small
      bowel SUVmax was lower after 24 hours (2.86 +/- 0.67 vs 3.73 +/- 1.08 [control];
      P ? .001) and 48 hours (2.78 +/- 0.73 vs 3.73 +/- 1.08 [control]; P ? .001) of
      metformin discontinuation versus no metformin discontinuation, but not for 48
      hours versus 24 hours of discontinuation (P = .57). Examination-day blood glucose
      levels increased after 48-hour withdrawal of metformin (8.41 mmol/L +/- 2.86 vs
      6.83 mmol/L +/- 2.13 [control]; P = .002). Conclusion Metformin discontinuation
      for 48 hours prior to PET/CT was associated with lower accumulation of
      fluorodeoxyglucose in the bowel, compared to when there was no discontinuation
      (control group) or 24-hour discontinuation of metformin. (c) RSNA, 2018.

PMID- 30106347
TI  - Mapping Drug Dose Distribution on CT Images Following Transarterial
      Chemoembolization with Radiopaque Drug-Eluting Beads in a Rabbit Tumor Model.
AB  - Purpose To correlate bead location and attenuation on CT images with the quantity
      and distribution of drug delivered to the liver following transarterial
      chemoembolization (TACE) with radiopaque drug-eluting beads (DEB) in a rabbit
      tumor model. Materials and Methods All procedures were performed with a protocol
      approved by the Institutional Animal Care and Use Committee. TACE was performed
      in rabbits (n = 4) bearing VX2 liver tumors by using radiopaque DEB (70-150 um)
      loaded with doxorubicin (DOX). Livers were resected 1 hour after embolization,
      immediately frozen, and cut by using liver-specific three-dimensional-printed
      molds for colocalization of liver specimens and CT imaging. DOX penetration into
      tissue surrounding beads was evaluated with fluorescence microscopy. DOX levels
      in liver specimens were predicted by using statistical models correlating DOX
      content measured in tissue with bead volume and attenuation measured on CT
      images. Model predictions were then compared with actual measured DOX
      concentrations to assess the models' predictive power. Results Eluted DOX
      remained in close proximity (<600 um) to beads in the liver 1 hour after TACE.
      Bead volume and attenuation measured on CT images demonstrated positive linear
      correlations (0.950 and 0.965, respectively) with DOX content in liver specimens.
      DOX content model predictions based on CT images were accurate compared with
      actual liver DOX levels at 1 hour. Conclusion CT may be used to estimate drug
      dose delivery and distribution in the liver following transarterial
      chemoembolization (TACE) with doxorubicin-loaded radiopaque drug-eluting beads
      (DEB). Although speculative, this informational map might be helpful in planning
      and understanding the spatial effects of TACE with DEB. (c) RSNA, 2018.

PMID- 30106350
TI  - Multiple Odontogenic Cysts and Intracranial Calcification: Gorlin-Goltz Syndrome.

PMID- 30106349
TI  - Disrespect and abuse in childbirth in Brazil: social activism, public policies
      and providers' training.
AB  - Brazil is a middle-income country with universal maternity care, mostly by
      doctors. The experience of normal birth often includes rigid routines, aggressive
      interventions, and abusive, disrespectful treatment. In Brazil, this has been
      referred to as dehumanised care and, more recently, as obstetric violence. Since
      the early 1990s, social movements (SM) have struggled to change practices, public
      policies and provider training. The aim of this paper is to describe and analyse
      the role of SM in promoting change in maternity care, and in provider training.
      In this integrative review using a gender-oriented approach, we searched the
      Scielo database and the Ministry of Health's (MofH) publications and edicts for
      institutional and research papers on SM initiatives addressing disrespect and
      abuse in the last 25 years (1993-2018) in Brazil, and their impact on public
      policies and training programmes. We analyse these groups of interrelated
      initiatives: (1) political actions of SM resulting in changes in public policies
      and legislation; (2) events organised by SM for diffusion of information to the
      public; (3) MofH policies to humanise childbirth with participation of SM; and
      (4) initiatives to change providers' training, including legal actions based on
      obstetric violence reports. To promote real change in maternity care, the
      progression of policies and enabling environment of laws, regulations, and broad
      dissemination of information, need to go hand in hand with changes in all health
      providers' training - including a solid base in ethics, gender and human rights.

PMID- 30106351
TI  - Pembrolizumab-induced Sarcoid-like Reactions during Treatment of Metastatic
      Melanoma.
AB  - Pembrolizumab is a programmed cell death protein 1, or PD-1, inhibitor therapy
      immunotherapy for patients with advanced melanoma. This report discusses a series
      of documented cases of sarcoid-like reactions associated with this therapy. Three
      patients with malignant melanoma developed metastatic disease and were treated
      with pembrolizumab immunotherapy. Subsequent imaging showed lymphadenopathy in
      the mediastinum and hilar regions that was confirmed to represent a sarcoid-like
      reaction at histologic examination. Radiologists should be aware of the
      association between pembrolizumab and the development of sarcoid-like reactions
      to avoid inaccurately ascribing these imaging findings to metastatic disease.
      Clinical presentation, biopsy, radiographic evidence of bilateral hilar
      lymphadenopathy (with paratracheal lymphadenopathy), and elevated serum
      angiotensin-converting enzyme levels aid in the diagnosis of sarcoid-like
      reactions and help avoid these reactions being mistaken for recurrent or
      metastatic disease.

PMID- 30106353
TI  - Dissecting Candida Pathobiology: Post-Translational Modifications on the Candida
      tropicalis Proteome.
AB  - Candida tropicalis belongs to the non-albicans group of Candida, and causes
      epidermal, mucosal, or systemic candidiasis in immunocompromised individuals.
      Although the prevalence of candidiasis has increased worldwide and non-albicans
      Candida (NAC) are becoming more significant, there are very few studies that
      focus on the NAC biology. Proteins and their post-translational modifications
      (PTMs) are an integral aspect in the pathobiology of such medically important
      fungi. Previously, we had reported the largest proteomic catalog of C.
      tropicalis. Notably, PTMs can be identified from proteomics data without a priori
      enrichment for a particular PTM, thus allowing broad-scale omics analyses. In
      this study, we developed the "PTM-Pro," a graphical user interface-based tool for
      identification and summary of high-confidence PTM sites based on statistical
      threshold of users' choice. We mined available proteomic data of C. tropicalis,
      and using PTM-Pro identified nearly 600 high-confidence PTM sites. The PTMs
      identified include phosphorylation of serine, threonine, and tyrosine;
      acetylation, crotonylation, methylation, and succinylation of lysine. These PTMs
      reside on biologically significant molecules, including histones, enzymes, and
      transcription factors. To our knowledge, this is the first report of PTMs in C.
      tropicalis and lays a foundation for future investigations of C. tropicalis PTMs.
      In addition, the PTM-Pro offers a graphical user interface tool for research on
      PTM sites in the field of proteomics.

PMID- 30106354
TI  - The Nile River Microbiome Reveals a Remarkably Stable Community Between Wet and
      Dry Seasons, and Sampling Sites, in a Large Urban Metropolis (Cairo, Egypt).
AB  - World freshwater supplies are in need of microbiome diversity analyses as a first
      step to future ecological studies, and to monitor water safety and quality. The
      Nile is a major north-flowing river in Africa that displays both spatial and
      temporal variations in its water quality. Here, we present the first microbiome
      analysis of the Nile River water in two seasons: (1) summer representing the wet
      season, and (2) winter representing the dry season, as sampled around Cairo, the
      capital of Egypt. Surface river water samples were collected from selected
      locations along the path of river, and the microbial composition was analyzed by
      next-generation sequencing of the 16S rRNA gene. We found a striking stability in
      the Nile microbiome community structure along the examined geographical urban
      sites and between the wet and dry seasons as evidenced by the high proportion of
      shared operational taxonomic unit values among all samples. The community was
      dominated by the Cyanobacteria (mainly Synechococcus), Actinobacteria candidate
      family (ACK-M1), and Proteobacteria (mainly family Comamonadaceae). Among these
      dominant taxa, Synechococcus exhibited seasonal driven variation in relative
      abundance. Other taxa were predominantly rare across all seasons and locations,
      including genera members of which have been implicated as pathogens such as
      Acinetobacter, Aeromonas, and Legionella. In addition, comparisons with data on
      freshwater microbiome in other world regions suggest that surface water
      communities in large rivers exhibit limited variation. Our results offer the
      first insights on microbial composition in one of the most notable rivers near a
      large metropolis.

PMID- 30106352
TI  - A Next-Generation Sequencing-Based Molecular Approach to Characterize a Tick
      Vector in Lyme Disease.
AB  - Next-generation sequencing approaches have revolutionized genomic medicine and
      enabled rapid diagnosis for several diseases. These approaches are widely used
      for pathogen detection in several infectious diseases. Lyme disease is a tick
      borne infectious disease, which affects multiple organs. The causative organism
      is a spirochete, Borrelia burgdorferi, which is transmitted by ticks. Lyme
      disease can be treated easily if detected early, but its diagnosis is often
      delayed or is incorrect leading to a chronic debilitating condition. Current
      confirmatory diagnostic tests for Lyme disease rely on detection of antigens
      derived from B. burgdorferi, which are prone to both false positives and false
      negatives. Instead of focusing only on the human host for the diagnosis of Lyme
      disease, one could also attempt to identify the vector (tick) and the causative
      organism carried by the tick. Since all ticks do not transmit Lyme disease, it
      can be informative to accurately identify the tick from the site of bite, which
      is often observed by the patient and discarded. However, identifying ticks based
      on morphology alone requires a trained operator and can still be incorrect. Thus,
      we decided to take a molecular approach by sequencing DNA and RNA from a tick
      collected from an individual bitten by the tick. Using next-generation
      sequencing, we confirmed the identity of the tick as a dog tick, Dermacentor
      variabilis, and did not identify any pathogenic bacterial sequences, including
      Borrelia species. Despite the limited availability of nucleotide sequences for
      many types of ticks, our approach correctly identified the tick species. This
      proof-of-principle study demonstrates the potential of next-generation sequencing
      in the diagnosis of tick-borne infections, which can also be extended to other
      zoonotic diseases.

PMID- 30106355
TI  - Kinematic patterns for hindlimb obstacle avoidance during sheep locomotion.
AB  - Functional recovery following general nerve reconstruction is often associated
      with poor results. Comparing to rat and mice experimental studies, there are much
      fewer investigations on nerve regeneration and repair in the sheep, and there are
      no studies on this subject using gait analysis in the sheep model as an
      assessment tool. Additionally, this is the first study evaluating obstacle
      negotiation and the compensatory strategies that take place at each joint in
      response to the obstacle during locomotion in the sheep model. This study aims to
      get kinematic data to serve as a template for an objective assessment of the
      ankle joint motion in future studies of common peroneal nerve (CP) injury and
      repair in the ovine model. Our results show that a moderately high obstacle set
      to 10% of the sheep's hindlimb length was associated to several spatial and
      temporal strategies in order to increase hoof height during obstacle negotiating.
      Sheep efficiently cleared an obstacle by increasing knee, ankle and
      metatarsophalangeal flexion during swing, whereas the hip joint is not affected.
      This study establishes the bounds of normal motion in the neurologically intact
      hindlimb when approached and cleared an obstacle and provides baseline data for
      further studies of peripheral nerve research in the ovine model.

PMID- 30106356
TI  - Biological embedding of neighborhood disadvantage and collective efficacy:
      Influences on chronic illness via accelerated cardiometabolic age.
AB  - The present study extends prior research on the link between neighborhood
      disadvantage and chronic illness by testing an integrated model in which
      neighborhood characteristics exert effects on health conditions through
      accelerated cardiometabolic aging. Hypotheses were tested using a sample of 408
      African Americans from the Family and Community Health Study. Using four waves of
      data spanning young adulthood (ages 18-29), we first found durable effects of
      neighborhood disadvantage on accelerated cardiometabolic aging and chronic
      illness. Then, we used marginal structural modeling to adjust for potential
      neighborhood selection effects. As expected, accelerated cardiometabolic aging
      was the biopsychosocial mechanism that mediated much of the association between
      neighborhood disadvantage and chronic illness. This finding provides additional
      support for the view that neighborhood disadvantage can influence morbidity and
      mortality by creating social contexts that becomes biologically embedded.
      Perceived neighborhood collective efficacy served to buffer the relationship
      between neighborhood disadvantage and biological aging, identifying neighborhood
      level resilience factor. Overall, our results indicate that neighborhood context
      serves as a fundamental cause of weathering and accelerated biological aging.
      Residing in a disadvantaged neighborhood increases biological wear and tear that
      ultimately leads to onset of chronic illness, but access to perceived collective
      efficacy buffers the impact of these neighborhood effects. From an intervention
      standpoint, identifying such an integrated model may help inform future health
      promoting interventions.

PMID- 30106358
TI  - Electroconvulsive therapy and later stroke in patients with affective disorders.
AB  - SummaryThe long-term effects of electroconvulsive therapy (ECT) on the risk of
      stroke are unknown. We examined the association between ECT and risk of incident
      or recurrent stroke. A cohort of 174 534 patients diagnosed with affective
      disorder between 2005 and 2016 in the Danish National Patient Registry were
      followed for stroke until November 2016. The association between ECT and stroke
      was analysed using Cox regression with multiple adjustment and propensity-score
      matching on sociodemographic and clinical variables. In 162 595 patients without
      previous stroke, 5781 (3.6%) were treated with ECT. The total number of patients
      developing stroke during follow-up was 3665, of whom 165 had been treated with
      ECT. In patients <50 years, ECT was not associated with stroke (adjusted hazard
      ratio (HR) = 1.29, 95% CI 0.87-1.93). In patients >=50, ECT was associated with a
      lower risk of stroke (adjusted HR = 0.69, 95% CI 0.57-0.89), but this estimate
      was likely influenced by competing mortality risk. Of 11 939 patients with a
      history of stroke, 228 (1.9%) were treated with ECT. During follow-up, 2330
      (19.5%) patients had a recurrence, of which 26 were patients treated with ECT.
      ECT was not associated with risk of a new event (HR = 0.69, 95% CI 0.46-1.00; P =
      0.05). ECT is not associated with an elevated risk of incident or recurrent
      stroke.Declaration of interestNone.

PMID- 30106357
TI  - Moving beyond categories and dimensions in personality pathology assessment and
      diagnosis.
AB  - It has been suggested that a dimensional model of personality pathology should be
      adopted for the development and refinement of personality disorder
      classification. In this article, the advantages and challenges of moving toward a
      dimensional model are briefly reviewed. However, it is suggested that although
      categories and dimensions are valuable frameworks for personality pathology
      diagnosis, an expansion beyond categories and dimensions is needed to improve the
      shortcoming seen in current diagnostic systems. Ideas and examples are offered
      for how this might occur.Declaration of interestNone.

PMID- 30106360
TI  - Head motion: the dirty little secret of neuroimaging in psychiatry.
AB  - Psychiatry is at a crossroads when choosing final samples for analysis of
      neuroimaging data. Many patient populations exhibit significantly increased
      motion in the scanner compared with healthy controls, suggesting that more
      patients would need to be excluded to obtain a clean sample. However, this need
      is often overshadowed by the extensive amount of time and effort required to
      recruit these valuable and uncommon samples. This commentary sheds light on the
      impact of motion on imaging studies, drawing examples from psychiatric patient
      samples to better understand how head motion can confound interpretation of
      clinically oriented questions. We discuss the impact of even subtle motion
      artifacts on the interpretation of results as well as how different levels of
      stringency in quality control can affect findings within nearly identical
      samples. We also summarize recent initiatives toward harmonization of quality
      control procedures as well as tools to prospectively and retrospectively correct
      for motion artifacts.

PMID- 30106359
TI  - ERbeta agonist alters RNA splicing factor expression and has a longer window of
      antidepressant effectiveness than estradiol after long-term ovariectomy.
AB  - BACKGROUND: Estrogen therapy (ET), an effective treatment for perimenopausal
      depression, often fails to ameliorate symptoms when initiated late after the
      onset of menopause. Our previous work has suggested that alternative splicing of
      RNA might mediate these differential effects of ET. METHODS: Female Sprague
      Dawley rats were treated with estradiol (E2) or vehicle 6 days (early ET) or 180
      days (late ET) after ovariectomy (OVX). We investigated the differential
      expression of RNA splicing factors and tryptophan hydroxylase 2 (TPH2) protein
      using a customized RT2 Profiler PCR Array, reverse-transcription polymerase chain
      reaction, immunoprecipitation and behaviour changes in clinically relevant early
      and late ET. RESULTS: Early ET, but not late ET, prolonged swimming time in the
      forced swim test and reduced anxiety-like behaviours in the elevated plus maze.
      It reversed OVX-increased (SFRS7 and SFRS16) or OVX-decreased (ZRSR2 and CTNNB1)
      mRNA levels of splicing factors and ERbeta splicing changes in the brains of OVX
      rats. Early ET, but not late ET, also increased the expression of TPH2 and
      decreased monoamine oxidase A levels in the dorsal raphe in the brains of OVX
      rats. In late ET, only diarylpropionitrile (an ERbeta-specific agonist) achieved
      similar results - not E2 (an ERalpha and ERbeta agonist) or propylpyrazoletriol
      (an ERalpha-specific agonist). LIMITATIONS: Our experimental paradigm mimicked
      early and late ET in the clinical setting, but the contribution of age and OVX
      might be difficult to distinguish. CONCLUSION: These findings suggest that ERbeta
      alternative splicing and altered responses in the regulatory system for serotonin
      may mediate the antidepressant efficacy of ET associated with the timing of
      therapy initiation. It is likely that ERbeta-specific ligands would be effective
      estrogen-based antidepressants late after the onset of menopause.

PMID- 30106361
TI  - Distinct pattern of neostriatal calcifications in dyskeratosis congenita: A case
      report and literature review.
AB  - Dyskeratosis congenita (DKC) is a rare, inherited disorder classically known by
      the triad of nail dystrophy, mucosal leukoplakia, and lacy reticulated skin
      hyperpigmentation. Bone marrow failure is a prominent feature and accounts for
      most deaths in these patients. Genetic mutations resulting in shortened telomeres
      have been shown to cause DKC, which is the basis for categorizing it as a
      "premature aging syndrome". Different modes of inheritance have been identified
      with X-linked recessive as the most common. There have been reports of
      intracranial calcifications on neuroradiology in a few cases of DKC, but no
      histopathologic illustration has been provided. We report a 20-year-old female
      patient with autosomal dominant DKC established by TINF2 gene mutation.
      Neostriatal calcifications with a distinctive pattern observed on neuroimaging
      were confirmed by postmortem microscopic examination. In contrast to the usual
      pattern of basal ganglia calcification, which starts in the globus pallidus, in
      this case the deposits were located in the caudate and putamen, sparing the
      globus pallidus. Iron deposits were also detected with similar distribution.
      Interestingly, staining for markers of brain aging (tau, amyloid, and p62)
      yielded negative results. These findings could not be attributed to any other
      condition (i.e., hypoparathyroidism, infections, etc.). Thus, we conclude that
      basal ganglia calcification can be a rare feature of DKC.?.

PMID- 30106362
TI  - Capecitabine bioequivalence in healthy volunteers.
AB  - Capecitabine is a prodrug and is selectively activated by tumor cells to its
      cytotoxic moiety, 5-fluorouracil, by thymidine phosphorylase, which is generally
      expressed at high levels in tumors. Clinical and pharmacokinetic studies of
      capecitabine have been performed in patients with cancer. This study aims to
      evaluate the bioequivalence of two capecitabine formulations (150-mg tablet)
      using healthy male subjects under nonfasting conditions. The study was conducted
      as an open, randomized, three-period, semi-replicated design with three sequences
      (RRT, RTR, TRR) with a 1-week washout interval. The subjects were selected for
      the study after having their health status previously assessed by a clinical
      evaluation and laboratory tests (biochemical and hematological parameters, and
      urinalysis). A single capecitabine tablet (150 mg) was given in each occasion.
      Plasma capecitabine concentrations were analyzed by liquid chromatography coupled
      with tandem mass spectrometry (HPLC/MS/MS) with positive ion electrospray
      ionization using multiple reactions monitoring (MRM). The geometric mean and 90%
      confidence intervals (CI) of capecitabine/Xeloda(r) (T/R) percent ratio were
      104.34% (98.74 - 110.25%) for AUClast, 103.06% (97.48 - 108.96%) for AUCinf, and
      104.07% (88.13 - 122.90%) for Cmax. Since the 90% CI for Cmax, AUClast, and
      AUCinf ratios were all inside the 80 - 125% interval proposed by the US Food and
      Drug Administration Agency, it was concluded that the capecitabine formulation
      elaborated by Eurofarma Laboratorios Ltda. is bioequivalent to Xeloda(r)
      formulation for both the rate and the extent of absorption. The drug was well
      tolerated by the subjects, indicating that it is safe to perform capecitabine
      bioequivalence studies in healthy male subjects.?.

PMID- 30106363
TI  - Development of clinical pharmacy services in Australia, Austria, Belgium, Bosnia
      Herzegovina, Canada, Germany, Japan, Kosovo, Switzerland, the Netherlands,
      Thailand, USA and correlation with educational standards, level of research, and
      implemen.
AB  - OBJECTIVE: This study aimed to compare determinants of professional development
      between different countries to identify barriers and facilitators of development
      towards clinical pharmacy services and stimulate discussion of under-used
      potential and opportunities. MATERIALS: The study was conceived as a survey. The
      questionnaire was administered to a group of experts. METHODS: The survey was
      conducted as a cross-sectional study with descriptive and correlation analysis. A
      questionnaire was developed and adjusted to the study focus, covering aspects on
      general regulations for community pharmacies, professional education,
      implementation of clinical pharmacy services, and research in patient care.
      Results were compared for analyses. RESULTS: A total of twelve countries were
      included in this survey. Pharmacy studies took between 4 and 6 years plus
      residency in most countries. Curricula remained drug-oriented only in Austria,
      Bosnia-Herzegovina, and Germany; these three countries had the least
      pharmacotherapy content in their curricula. Canada, the USA, and Australia have
      established clinical pharmacy services in almost all fields of practice. Most
      other countries have implemented at least some clinical services, with the
      exception of Bosnia-Herzegovina, Germany, and Kosovo. The correlation coefficient
      between education, research, and implementation was 0.91. CONCLUSION: The results
      of the survey show that clinical pharmacy services are established to very
      different extents among the participating countries. The strong correlation
      suggests that achieving a successful transition in professional practice needs to
      address several aspects of education and research to reach progress. The
      collected data might help to identify potential areas of improvement to foster
      implementation of clinical pharmacy services.?.

PMID- 30106364
TI  - Subclinical metabolic and cardiovascular abnormalities in autosomal dominant
      polycystic kidney disease?.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent
      genetic kidney disease. It carries high lifetime morbidity not only due to
      chronic kidney disease, but also due to a higher risk of cardiovascular death.
      Multiple metabolic abnormalities associated with ADPKD including insulin
      resistance and hyperlipidemia as well as subclinical cardiovascular
      abnormalities, such as left ventricular hypertrophy (LVH), contribute to this
      cardiovascular risk. These conditions may manifest before evidence of worsening
      estimated glomerular filtration rate (eGFR). Renal oxidative stress also occurs
      early in the disease and is a driver of ADPKD progression. Animal models have
      shown that calorie restriction may mitigate these inflammatory processes. Further
      research is required to show whether attenuation of metabolic abnormalities
      associated with ADPKD may improve renal and cardiovascular morbidity.?.

PMID- 30106365
TI  - Neutropenia related to an azathioprine metabolic disorder induced by an inosine
      triphosphate pyrophosphohydrolase (ITPA) gene mutation in a patient with PR3-ANCA
      positive microscopic polyangiitis?.
AB  - A 68-year-old Japanese man was monitored for chronic kidney disease (CKD), with
      unknown primary disease starting in 2014. His serum creatinine (sCr) was stable
      at ~ 2.5 mg/dL for ~ 2 years. Two weeks before admission, he had bloody sputum,
      and sCr increased to 4.63 mg/dL. Soon after admission, the patient developed a
      high fever with pigment spots on the legs. A kidney biopsy was performed. The
      kidney specimens showed necrotizing and crescentic glomerulonephritis without
      granuloma formation. An additional blood-sampling test revealed high titers of
      PR3-ANCA, and we diagnosed PR3-ANCA-positive microscopic polyangiitis (MPA).
      Treatment with intravenous steroid pulse therapy and intermittent pulse
      intravenous cyclophosphamide therapy was started for remission induction. With
      these treatments, sCr improved to ~ 3.0 mg/dL. Azathioprine (AZA) was added for
      remission-maintenance therapy. Three days later, the dose of AZA was increased
      from 50 to 100 mg/day, and the number of neutrophils decreased to 30/MUL. After
      withdrawal of AZA, neutrophil levels gradually recovered. We suspected that an
      abnormal metabolism of AZA was responsible for the neutropenia. Therefore, we
      analyzed three AZA metabolism-associated genes for mutations: thiopurine S
      methyltransferase (TPMT), inosine triphosphate pyrophosphohydrolase (ITPA), and
      nucleoside diphosphate linked moiety X-type motif 15 (NUDT15), and we identified
      ITPA 94C>A mutation. This was a rare case of PR3-positive MPA with AZA-induced
      severe neutropenia that was possibly due to an ITPA gene mutation. This case
      suggests that ITPA gene mutation is related to the adverse reactions of AZA in
      Japanese patients. We have to pay attention to severe neutropenia when we use
      AZA, especially in Asian patients with CKD.?.

PMID- 30106366
TI  - Prevention of contrast-induced nephropathy with prostaglandin E1 in patients
      undergoing percutaneous coronary procedures: A meta-analysis of 24 randomized
      controlled trials?.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is the third most common cause of
      acute kidney injury in hospitalized patients. There have been many conflicting
      results across trials that have evaluated the prophylactic efficacy of
      prostaglandin E1 (PGE1) for prevention of CIN in patients undergoing percutaneous
      coronary procedures. PGE1 may have renal-protective effects due to its
      pleiotropic properties. The aim of this study was to evaluate the efficacy of
      PGE1 in preventing CIN. MATERIALS AND METHODS: We searched PubMed, Embase,
      Cochrane Library, Chinese Biomedical Literature, China National Knowledge
      Infrastructure, VIP Information/Chinese Scientific Journals, and WANFANG
      databases for randomized controlled trials (RCTs) comparing the preventive
      effects of PGE1 versus controls (conventional hydration, no PGE1, or placebo) on
      CIN in patients undergoing percutaneous coronary procedures from January 1999 to
      June 2016. Study characteristics and outcome data were abstracted by two
      independent reviewers; the risk of bias was also assessed by two reviewers.
      RESULTS: 24 RCTs involving 3,915 patients were included. Compared with controls,
      PGE1 reduced the risk of CIN (risk ratio: 0.40, 95% confidence interval (CI):
      0.33, 0.48; p < 0.01). Serum creatinine levels in the PGE1 groups were
      significantly lower than in the control groups at 24, 48, and 72 hours after
      operation (mean difference (MD): -10.06, 95% CI: -16.94, -3.19; MD: -15.47, 95%
      CI: -21.75, -9.18; and MD: -11.15, 95% CI: -14.40, -7.91, respectively). Cystatin
      C was significantly lower for the PGE1 group than the control groups at 24, 48,
      and 72 hours after operation (MD: -0.24, 95% CI: -0.40, -0.07; MD: -0.34, 95% CI:
      -0.53, -0.14; and MD: -0.32, 95% CI: -0.49, -0.15, respectively). CONCLUSION:
      PGE1 may play an important role in reducing the incidence of CIN in patients
      undergoing percutaneous coronary procedures.?.

PMID- 30106367
TI  - ANCA-associated vasculitis in scleroderma: A renal perspective?.
AB  - AIMS: Overlap syndrome of ANCA-associated vasculitis (AAV) and scleroderma (SSc)
      is rare with conflicting data on renal outcomes. We describe the clinical
      characteristics and treatment outcome of ANCA-associated glomerulonephritis (AAG)
      in SSc patients followed at a single center. MATERIALS AND METHODS: We conducted
      a retrospective study of 3,570 patients in our SSc database to identify SSc
      patients who subsequently developed AAV with renal involvement. Patient
      demographics, serology, renal function, renal histology, and treatment outcomes
      were assessed. RESULTS: Of the 3,570 patients, we identified 7 patients who
      developed acute glomerulonephritis, and all were ANCA positive. The mean age at
      SSc diagnosis was 47 years, 4 patients were female, and 6 had diffuse SSc. Anti
      nuclear antibody (ANA) was positive in all. Mean time of onset of AAV from time
      of diagnosis of SSc was 6 years, and all were myeloperoxidase (MPO) positive.
      Patients presented with hematuria, proteinuria, with or without rise in serum
      creatinine, and all patients had biopsy-proven crescentic glomerulonephritis. One
      patient required dialysis at presentation. Five patients were treated with
      cyclophosphamide and steroids, and 2 were treated with rituximab and steroids. Of
      the 7 patients, 4 did not receive maintenance immunosuppression. Three patients
      died, and 1 of them experienced relapse with fulminant alveolar hemorrhage.
      CONCLUSION: AAG in SSc is rare, with disease manifestation and course similar to
      that of AAV. This case series demonstrates that disease remission can be achieved
      with standard induction therapy. Vasculitis relapse can occur, and similar to
      idiopathic AAV, maintenance immunosuppression should be initiated to maintain
      remission.?.

PMID- 30106368
TI  - Chronic tubulointerstitial kidney disease in untreated adenine phosphoribosyl
      transferase (APRT) deficiency: A case report?.
AB  - Adenine phosphoribosyltransferase (APRT) deficiency (OMIM #614723) is a rare
      autosomal recessive defect in the purine salvage pathway that causes excessive
      production of 2,8-dihydroxyadenine, leading to nephrolithiasis and chronic kidney
      disease (CKD). This case report describes the natural history of CKD in untreated
      APRT deficiency. We describe a novel APRT mutation (chr16:88877985 G / C; c.195
      C>/G; p.His54Asp) presenting with CKD without nephrolithiasis. The patient
      initially required dialysis, but kidney function improved with allopurinol. We
      reviewed APRT deficiency reported in the literature to determine the loss of
      kidney function in individuals with untreated APRT deficiency and its
      relationship to nephrolithiasis. We identified 95 individuals in whom kidney
      function was assessed prior to treatment. There was a bimodal distribution of
      kidney failure. AKI occurred frequently in childhood due to obstructing
      nephrolithiasis or crystalline nephropathy and was usually reversible. CKD
      developed after age 20 in all patients irrespective of nephrolithiasis history,
      with 36/42 patients > 40 years of age having at least stage 3 CKD, and 24/42
      having an eGFR > 10 mL/min/1.73m2 or being on dialysis. There were 13 adults
      without nephrolithiasis and 50 adults with nephrolithiasis. The mean age of end
      stage renal diesease (ESRD) was 50.52 +/- 13.9 for those without nephrolithiasis
      and 43.4 +/- 15.8 years for those with nephrolithiasis (p = 0.24). APRT
      deficiency is associated with slowly progressive CKD that occurs independently of
      nephrolithiasis. Diagnosis should be considered in all individuals with chronic
      tubulointerstitial kidney disease, with or without the presence of
      nephrolithiasis. In our patient, allopurinol 300 mg/day resulted in improvement
      of kidney function.?.

PMID- 30106369
TI  - The impact of a remote monitoring system of healthcare resource consumption in
      patients on automated peritoneal dialysis (APD): A simulation study?.
AB  - AIMS: Remote monitoring (RM) can improve management of chronic diseases. We
      evaluated the impact of RM in automated peritoneal dialysis (APD) in a simulation
      study. MATERIALS AND METHODS: We simulated 12 patient scenarios with common
      clinical problems and estimated the likely healthcare resource consumption with
      and without the availability of RM (RM+ and RM- groups, respectively). Scenarios
      were evaluated 4 times by randomly allocated nephrologist-nurse teams or
      nephrologist-alone assessors. RESULTS: The RM+ group was assessed as having
      significantly lower total healthcare resource consumption compared with the RM-
      group (36.8 vs. 107.5 total episodes of resource consumption, p = 0.002). The RM+
      group showed significantly lower "unplanned hospital visits" (2.3 vs. 11.3, p =
      0.005), "emergency room visits" (0.5 vs. 5.3, p = 0.003), "home visits" (0.5 vs.
      5.8, p = 0.016), "exchanges over the telephone" (18.5 vs. 57.8, p = 0.002), and
      "change to hemodialysis" (0.5 vs. 2.5, p = 0.003). Evaluations did not differ
      between nephrologist-nurse teams vs. nephrologist-alone assessors. CONCLUSION: RM
      can be expected to reduce healthcare resource consumption in APD patients.?.

PMID- 30106370
TI  - National outcomes of in-hospital cardiopulmonary resuscitation in patients with
      acute kidney injury: years 2005 - 2011?.
AB  - BACKGROUND: There is paucity of data on the outcomes of in-hospital
      cardiopulmonary resuscitation (CPR) in patients with acute kidney injury (AKI).
      We analyzed the impact of acute kidney injury on in-hospital CPR-related
      outcomes. MATERIALS AND METHODS: We analyzed data from Nationwide Inpatient
      Sample (NIS 2005 - 2011) including patients with and without AKI who had
      undergone in-hospital CPR. Baseline characteristics, in-hospital complications
      and discharge outcomes were compared between the two groups. We determined the
      effect of AKI on length of hospital stay, discharge destination, hospital
      mortality, survival trends, and discharge to home. RESULTS: 180,970 patients with
      primary or secondary diagnosis of AKI underwent in-hospital CPR compared to
      323,620 patients without AKI. Unadjusted in-hospital mortality rates were higher
      in the AKI group (78.2 vs. 71.8%, p < 0.0001). After adjusting for age, sex, and
      potential confounders, patients in the AKI group had higher odds of mortality
      with odds ratio 1.3, 95% confidence interval 1.2 - 1.4, p < 0.0001. Survivors in
      the AKI group were more likely to be discharged to nursing homes and had higher
      mean hospitalization charges. In 2011 compared with 2005, there was an improved
      survival after CPR and higher rates of discharges to home. There was no
      significant change in the mean length of hospital stay between these time periods
      (p = 0.4). CONCLUSION: AKI independently increases the odds of in-hospital
      mortality and nursing home placement after in-hospital CPR. These data may
      facilitate CPR discussions and decision-making in critically ill patients.?.

PMID- 30106372
TI  - Stimulus vignetting and orientation selectivity in human visual cortex.
AB  - Neural selectivity to orientation is one of the simplest and most thoroughly
      studied cortical sensory features. Here, we show that a large body of research
      that purported to measure orientation tuning may have in fact been inadvertently
      measuring sensitivity to second-order changes in luminance, a phenomenon we term
      'vignetting'. Using a computational model of neural responses in primary visual
      cortex (V1), we demonstrate the impact of vignetting on simulated V1 responses.
      We then used the model to generate a set of predictions, which we confirmed with
      functional MRI experiments in human observers. Our results demonstrate that
      stimulus vignetting can wholly determine the orientation selectivity of responses
      in visual cortex measured at a macroscopic scale, and suggest a reinterpretation
      of a well-established literature on orientation processing in visual cortex.

PMID- 30106371
TI  - Functional gradients of the cerebellum.
AB  - A central principle for understanding the cerebral cortex is that macroscale
      anatomy reflects a functional hierarchy from primary to transmodal processing. In
      contrast, the central axis of motor and nonmotor macroscale organization in the
      cerebellum remains unknown. Here we applied diffusion map embedding to resting
      state data from the Human Connectome Project dataset (n = 1003), and show for the
      first time that cerebellar functional regions follow a gradual organization which
      progresses from primary (motor) to transmodal (DMN, task-unfocused) regions. A
      secondary axis extends from task-unfocused to task-focused processing. Further,
      these two principal gradients revealed novel functional properties of the well
      established cerebellar double motor representation (lobules I-VI and VIII), and
      its relationship with the recently described triple nonmotor representation
      (lobules VI/Crus I, Crus II/VIIB, IX/X). Functional differences exist not only
      between the two motor but also between the three nonmotor representations, and
      second motor representation might share functional similarities with third
      nonmotor representation.

PMID- 30106374
TI  - Framing orientation selectivity.
AB  - The ongoing debate on the neural basis of orientation selectivity in the primary
      visual cortex continues.

PMID- 30106375
TI  - The adipocyte hormone leptin sets the emergence of hippocampal inhibition in
      mice.
AB  - Brain computations rely on a proper balance between excitation and inhibition
      which progressively emerges during postnatal development in rodent. gamma
      Aminobutyric acid (GABA) neurotransmission supports inhibition in the adult brain
      but excites immature rodent neurons. Alterations in the timing of the GABA switch
      contribute to neurological disorders, so unveiling the involved regulators may be
      a promising strategy for treatment. Here we show that the adipocyte hormone
      leptin sets the tempo for the emergence of GABAergic inhibition in the newborn
      rodent hippocampus. In the absence of leptin signaling, hippocampal neurons show
      an advanced emergence of GABAergic inhibition. Conversely, maternal obesity
      associated with hyperleptinemia delays the excitatory to inhibitory switch of
      GABA action in offspring. This study uncovers a developmental function of leptin
      that may be linked to the pathogenesis of neurological disorders and helps
      understanding how maternal environment can adversely impact offspring brain
      development.

PMID- 30106373
TI  - The role of Pitx2 and Pitx3 in muscle stem cells gives new insights into P38alpha
      MAP kinase and redox regulation of muscle regeneration.
AB  - Skeletal muscle regeneration depends on satellite cells. After injury these
      muscle stem cells exit quiescence, proliferate and differentiate to regenerate
      damaged fibres. We show that this progression is accompanied by metabolic changes
      leading to increased production of reactive oxygen species (ROS). Using Pitx2/3
      single and double mutant mice that provide genetic models of deregulated redox
      states, we demonstrate that moderate overproduction of ROS results in premature
      differentiation of satellite cells while high levels lead to their senescence and
      regenerative failure. Using the ROS scavenger, N-Acetyl-Cysteine (NAC), in
      primary cultures we show that a physiological increase in ROS is required for
      satellite cells to exit the cell cycle and initiate differentiation through the
      redox activation of p38alpha MAP kinase. Subjecting cultured satellite cells to
      transient inhibition of P38alpha MAP kinase in conjunction with NAC treatment
      leads to their rapid expansion, with striking improvement of their regenerative
      potential in grafting experiments.

PMID- 30106377
TI  - FluoEM, virtual labeling of axons in three-dimensional electron microscopy data
      for long-range connectomics.
AB  - The labeling and identification of long-range axonal inputs from multiple sources
      within densely reconstructed electron microscopy (EM) datasets from mammalian
      brains has been notoriously difficult because of the limited color label space of
      EM. Here, we report FluoEM for the identification of multi-color fluorescently
      labeled axons in dense EM data without the need for artificial fiducial marks or
      chemical label conversion. The approach is based on correlated tissue imaging and
      computational matching of neurite reconstructions, amounting to a virtual color
      labeling of axons in dense EM circuit data. We show that the identification of
      fluorescent light- microscopically (LM) imaged axons in 3D EM data from mouse
      cortex is faithfully possible as soon as the EM dataset is about 40-50 um in
      extent, relying on the unique trajectories of axons in dense mammalian neuropil.
      The method is exemplified for the identification of long-distance axonal input
      into layer 1 of the mouse cerebral cortex.

PMID- 30106380
TI  - Phase diagram for the Harper model of the honeycomb lattice.
AB  - The Harper equation arising out of a tight-binding model of electrons on a
      honeycomb lattice subject to a uniform magnetic field perpendicular to the plane
      is studied. Contrasting and complementary approaches involving von Neumann
      entropy, fidelity, fidelity susceptibility, and multifractal analysis are
      employed to characterize the phase diagram. Remarkably even in the absence of the
      quasi-periodic on-site potential term, the Hamiltonian allows for a metal
      insulator transition. The phase diagram consists of three phases: two metallic
      phases and an insulating phase. A variant model where next nearest neighbor
      hopping is included, exhibits a mobility edge and does not allow for a simple
      single phase diagram characterizing all the eigenstates.

PMID- 30106376
TI  - The adhesion function of the sodium channel beta subunit (beta1) contributes to
      cardiac action potential propagation.
AB  - Computational modeling indicates that cardiac conduction may involve ephaptic
      coupling - intercellular communication involving electrochemical signaling across
      narrow extracellular clefts between cardiomyocytes. We hypothesized that
      beta1(SCN1B) -mediated adhesion scaffolds trans-activating NaV1.5 (SCN5A)
      channels within narrow (<30 nm) perinexal clefts adjacent to gap junctions (GJs),
      facilitating ephaptic coupling. Super-resolution imaging indicated preferential
      beta1 localization at the perinexus, where it co-locates with NaV1.5. Smart patch
      clamp (SPC) indicated greater sodium current density (INa) at perinexi, relative
      to non-junctional sites. A novel, rationally designed peptide, betaadp1, potently
      and selectively inhibited beta1-mediated adhesion, in electric cell-substrate
      impedance sensing studies. betaadp1 significantly widened perinexi in guinea pig
      ventricles, and selectively reduced perinexal INa, but not whole cell INa, in
      myocyte monolayers. In optical mapping studies, betaadp1 precipitated
      arrhythmogenic conduction slowing. In summary, beta1-mediated adhesion at the
      perinexus facilitates action potential propagation between cardiomyocytes, and
      may represent a novel target for anti-arrhythmic therapies.

PMID- 30106378
TI  - Prognostication of chronic disorders of consciousness using brain functional
      networks and clinical characteristics.
AB  - Disorders of consciousness are a heterogeneous mixture of different diseases or
      injuries. Although some indicators and models have been proposed for
      prognostication, any single method when used alone carries a high risk of false
      prediction. This study aimed to develop a multidomain prognostic model that
      combines resting state functional MRI with three clinical characteristics to
      predict one year-outcomes at the single-subject level. The model discriminated
      between patients who would later recover consciousness and those who would not
      with an accuracy of around 88% on three datasets from two medical centers. It was
      also able to identify the prognostic importance of different predictors,
      including brain functions and clinical characteristics. To our knowledge, this is
      the first reported implementation of a multidomain prognostic model that is based
      on resting state functional MRI and clinical characteristics in chronic disorders
      of consciousness, which we suggest is accurate, robust, and interpretable.

PMID- 30106379
TI  - Direct visualization of a native Wnt in vivo reveals that a long-range Wnt
      gradient forms by extracellular dispersal.
AB  - Wnts are evolutionarily conserved signaling proteins with essential roles in
      development and disease that have often been thought to spread between cells and
      signal at a distance. However, recent studies have challenged this model, and
      whether long-distance extracellular Wnt dispersal occurs and is biologically
      relevant is debated. Understanding fundamental aspects of Wnt dispersal has been
      limited by challenges with observing endogenous ligands in vivo, which has
      prevented directly testing hypotheses. Here, we have generated functional,
      fluorescently tagged alleles for a C. elegans Wnt homolog and for the first time
      visualized a native, long-range Wnt gradient in a living animal. Live imaging of
      Wnt along with source and responding cell membranes provided support for free,
      extracellular dispersal. By limiting Wnt transfer between cells, we confirmed
      that extracellular spreading shapes a long-range gradient and is critical for
      neuroblast migration. These results provide direct evidence that Wnts spread
      extracellularly to regulate aspects of long-range signaling.

PMID- 30106381
TI  - Activity-dependent neuroprotective protein deficiency models synaptic and
      developmental phenotypes of autism-like syndrome.
AB  - Previous findings showed that in mice, complete knockout of activity-dependent
      neuroprotective protein (ADNP) abolishes brain formation, while
      haploinsufficiency (Adnp+/-) causes cognitive impairments. We hypothesized that
      mutations in ADNP lead to a developmental/autistic syndrome in children. Indeed,
      recent phenotypic characterization of children harboring ADNP mutations (ADNP
      syndrome children) revealed global developmental delays and intellectual
      disabilities, including speech and motor dysfunctions. Mechanistically, ADNP
      includes a SIP motif embedded in the ADNP-derived snippet drug candidate NAP
      (NAPVSIPQ, also known as CP201), which binds to microtubule end-binding protein
      3, essential for dendritic spine formation. Here, we established a unique
      neuronal membrane-tagged, GFP-expressing Adnp+/- mouse line allowing in vivo
      synaptic pathology quantification. We discovered that Adnp deficiency reduced
      dendritic spine density and altered synaptic gene expression, both of which were
      partly ameliorated by NAP treatment. Adnp+/-mice further exhibited global
      developmental delays, vocalization impediments, gait and motor dysfunctions, and
      social and object memory impairments, all of which were partially reversed by
      daily NAP administration (systemic/nasal). In conclusion, we have connected ADNP
      related synaptic pathology to developmental and behavioral outcomes, establishing
      NAP in vivo target engagement and identifying potential biomarkers. Together,
      these studies pave a path toward the clinical development of NAP (CP201) for the
      treatment of ADNP syndrome.

PMID- 30106383
TI  - Erratum.

PMID- 30106384
TI  - Erratum.

PMID- 30106385
TI  - Developing a Topology of Syphilis in the United States.
AB  - BACKGROUND: In the United States, reported rates of syphilis continue to
      increase. Co-occurring epidemics of syphilis among men who have sex with men
      (MSM) and heterosexual populations create challenges for the prioritization of
      resources and the implementation of context-specific interventions. METHODS:
      State was the unit of analysis and was restricted to the 44 states with the most
      complete data of sex or sex partners for their reported adult syphilis cases.
      States were classified as high, medium, or low for reported congenital syphilis
      (CS) and MSM primary and secondary (P&S) syphilis rates. Average values of a
      range of ecologic state level variables were examined among the 9 categories
      created through the cross-tabulation of CS and MSM P&S syphilis rates. Patterns
      among ecologic factors were assessed across the 9 categories of states' syphilis
      rates. RESULTS: Among the 44 states categorized, 4 states had high rates of both
      CS and MSM P&S syphilis in 2015, whereas 12 states fell into the medium/medium
      category and 7 into the low category. Six states had high CS and medium MSM
      syphilis and 4 states had medium CS but high MSM syphilis. Several area-level
      factors, including violent crime, poverty, insurance status, household structure
      and income, showed qualitative patterns with higher rates of CS and MSM P&S
      syphilis. Higher proportions of urban population were found among states with
      higher CS rates; no trend was seen with respect to urbanity and MSM P&S syphilis.
      CONCLUSIONS: Several area-level factors were associated with CS and MSM P&S
      syphilis in similar ways, whereas other ecologic factors functioned differently
      with respect to the 2 epidemics. Explorations of community and area-level factors
      may shed light on novel opportunities for population specific prevention of
      syphilis.

PMID- 30106382
TI  - Survival signal REG3alpha prevents crypt apoptosis to control acute
      gastrointestinal graft-versus-host disease.
AB  - Graft-versus-host disease (GVHD) in the gastrointestinal (GI) tract remains the
      major cause of morbidity and nonrelapse mortality after BM transplantation (BMT).
      The Paneth cell protein regenerating islet-derived 3alpha (REG3alpha) is a
      biomarker specific for GI GVHD. REG3alpha serum levels rose in the systematic
      circulation as GVHD progressively destroyed Paneth cells and reduced GI
      epithelial barrier function. Paradoxically, GVHD suppressed intestinal REG3gamma
      (the mouse homolog of human REG3alpha), and the absence of REG3gamma in BMT
      recipients intensified GVHD but did not change the composition of the microbiome.
      IL-22 administration restored REG3gamma production and prevented apoptosis of
      both intestinal stem cells (ISCs) and Paneth cells, but this protection was
      completely abrogated in Reg3g-/- mice. In vitro, addition of REG3alpha reduced
      the apoptosis of colonic cell lines. Strategies that increase intestinal
      REG3alpha/gamma to promote crypt regeneration may offer a novel,
      nonimmunosuppressive approach for GVHD and perhaps for other diseases involving
      the ISC niche, such as inflammatory bowel disease.

PMID- 30106387
TI  - Efficacy of Resuscitative Transfusion With Hemoglobin Vesicles in the Treatment
      of Massive Hemorrhage in Rabbits With Thrombocytopenic Coagulopathy and Its
      Effect on Hemostasis by Platelet Transfusion.
AB  - INTRODUCTION: We have developed hemoglobin vesicles (HbVs) as a substitute for
      red blood cells (RBCs). We investigated the efficacy of HbV transfusion in the
      treatment of massive hemorrhage in rabbits in the setting of thrombocytopenic
      coagulopathy, focusing on the efficacy of hemostasis by subsequent platelet
      transfusion. METHODS: Thrombocytopenic coagulopathy was induced in rabbits by
      repeated blood withdrawal and isovolemic retransfusion of autologous RBC
      (platelet counts <45,000/MUL). A penetrating liver injury was then made. For 30
      min, bleeding volume was measured every 10 min, after which subjects were
      transfused with an equivalent volume of stored RBC, HbV, or platelet poor plasma
      (PPP) to compensate for blood loss, simulating initial prehospital resuscitation.
      Thereafter, we transfused platelet rich plasma (PRP) to stop bleeding, which
      simulated inhospital resuscitation. RESULTS: During the initial resuscitation,
      the HbV group was similar to the RBC group (but not the PPP group) in their
      hemodynamics and tissue circulation/oxygenation as assessed by plasma lactate
      levels. All rabbits showed similar bleeding volumes (20-30 mL) in this period.
      HbV-transfused rabbits sustained hemoglobin levels, but showed lower hematocrit
      levels compared with RBC-transfused rabbits. Subsequent PRP transfusion
      effectively stopped bleeding in all RBC-transfused rabbits (6/6) and most HbV
      transfused rabbits (7/8) but not PPP-transfused rabbits (2/8). In addition, 83%
      of RBC-transfused rabbits and 75% of HbV-transfused rabbits survived for 24 h,
      although no PPP-transfused rabbits survived. HbV transfusion did not scavenge
      nitric oxide in rabbits. CONCLUSIONS: HbV transfusion effectively rescued rabbits
      from severe hemorrhage with coagulopathy, without disturbing hemostasis after the
      platelet transfusion. HbV transfusion may be practical and useful in prehospital
      resuscitation.

PMID- 30106386
TI  - Old Pathogen, New Challenges: A Narrative Review of the Multilevel Drivers of
      Syphilis Increasing in American Men Who Have Sex With Men.
AB  - Since the turn of the current century, syphilis incidence and prevalence have
      been increasing more rapidly among men who have sex with men (MSM) than any other
      US subpopulation, exceeding their previously high rates in the 1970s and 1980s,
      before the AIDS epidemic. The reasons for these trends are multifactorial and
      complex, involving individual behavioral, sociocultural, structural, and
      biological factors, which will be reviewed in this article. Men who have sex with
      men tend to have more sexual partners than heterosexuals, and engage in practices
      (e.g., anal sex) that are highly efficient for syphilis transmission and
      nondetection of primary chancres. In the era of highly active antiretroviral
      therapy rendering adherent patients noninfectious and the use of preexposure
      prophylaxis, there is substantially less concern about HIV transmission and
      acquisition among MSM, resulting in higher levels of condomless sex. The
      increased concentration of syphilis among black MSM is partially related to
      assortative mixing, that is, black MSM being more likely to have other black sex
      partners, as well as decreased access to preventive services and treatment due to
      economic marginalization, Societal rejection and discrimination may also
      potentiate factors that may increase sexual risks resulting in syphilis, for
      example, depression and substance use. The anticipation of experiencing
      homophobic discrimination in health care settings may lead many sexually active
      MSM to delay needed screening and treatment, thus being infectious to partners
      for longer periods than other populations. To effectively control the syphilis
      epidemic among MSM, scaling up a combination of programs, ranging from enhanced
      community education to training clinicians and health care systems to provide
      culturally competent care, will be necessary.

PMID- 30106388
TI  - Postoperative Complications in Dialysis-Dependent Patients Undergoing Elective
      Decompression Surgery Without Fusion or Instrumentation for Degenerative Cervical
      or Lumbar Lesions.
AB  - STUDY DESIGN: This was a single-institute retrospective study. OBJECTIVE: To
      evaluate postoperative complications in dialysis-dependent patients undergoing
      elective cervical and lumbar decompression surgery. SUMMARY OF BACKGROUND DATA:
      Spinal surgery in dialysis-dependent patients is very challenging due to the high
      risk of serious postoperative complications and mortality associated with their
      fragile general condition. However, the outcome of decompression surgery alone
      has not been evaluated in such patients. METHODS: An electronic medical record
      review showed that 338 and 615 patients had undergone cervical and lumbar spine
      posterior decompression, respectively. Among them, 48 and 42, respectively were
      dialysis-dependent patients. Postoperative complications were compared between
      dialysis-dependent and non-dialysis-dependent patients. RESULTS: Among patients
      who underwent cervical decompression, the rate of perioperative blood transfusion
      in dialysis-dependent patients (14.6%) was significantly higher than that in non
      dialysis-dependent patients (0.7%). No severe complications or mortality occurred
      in association with cervical decompression. The incidence of postoperative
      complications in dialysis-dependent patients (6.3%) was not significantly
      different from that in non-dialysis-dependent patients (4.1%). Among patients who
      underwent lumbar decompression, the rate of perioperative transfusion in dialysis
      dependent patients (11.9%) was also significantly higher than that in non
      dialysis-dependent patients (0.7%). With respect to severe complications among
      patients who underwent lumbar decompression, cerebral hemorrhage occurred in one
      dialysis-dependent patient, and no mortality occurred. The incidence of
      postoperative complications in dialysis-dependent patients (9.2%) was not
      significantly different from that in non-dialysis-dependent patients (6.8%).
      CONCLUSION: Among patients who underwent posterior decompression alone for
      cervical or lumbar lesions, the rate of perioperative blood transfusion was
      significantly higher in dialysis-dependent than in non-dialysis-dependent
      patients. However, the postoperative rates of severe complications and mortality
      were not significantly different between the two groups. Therefore, decompression
      surgery alone is considered a rational surgical method with less invasiveness for
      dialysis-dependent patients with a fragile general condition. LEVEL OF EVIDENCE:
      3.

PMID- 30106389
TI  - Evaluation of a Combination of Waveform Amplitude and Peak Latency in
      Intraoperative Spinal Cord Monitoring.
AB  - STUDY DESIGN: Retrospective study. OBJECTIVE: The goal of the study was to
      investigate the significance of a change in latency in monitoring of transcranial
      muscle-action potential (Tc-MsEP) waveforms. SUMMARY OF BACKGROUND DATA: Tc-MsEP
      has become a common approach in spine surgery due to its sensitivity and
      importance in motor function. Many reports have defined the alarm point of Tc
      MsEP waveform as a particular decrease in amplitude, but evaluation of the
      waveform latency has not attracted as much attention. METHODS: The subjects were
      70 patients who underwent spine surgery using intraoperative Tc-MsEP monitoring.
      The peak latency was defined as the period from stimulation until the waveform
      amplitude reached its peak. Relationships with postoperative paralysis were
      examined separately for latency delays of 5% or more and 10% or more, and in
      combination with a decrease in amplitude of 70% or more from baseline. RESULTS:
      Acceptable baseline Tc-MsEP responses were obtained from 1225 of 1372 muscles in
      the extremities (89.3%). Seven of the 70 patients (10%) had postoperative
      paralysis. A decrease in intraoperative amplitude of 70% or more from baseline
      occurred in 25 cases, with sensitivity 100%, specificity 71%, false positive rate
      29%, and positive predictive value (PPV) 28% for prediction of postoperative
      paralysis. Compared to baseline, 15 cases had a latency delay of 5% or more,
      which gave a sensitivity of 100%, specificity of 87%, false positive rate of 0%,
      and PPV 47%, and 8 cases had a delay of 10% or more, which gave a sensitivity of
      86%, specificity of 97%, false positive rate of 3%, and PPV 75%. A combination of
      a decrease in amplitude of 70% or more from baseline and a delay in latency of
      10% or more from baseline had a sensitivity of 86%, specificity of 98%, and a
      false positive rate of 2%, and PPV 86%. CONCLUSION: Combined use of latency and
      amplitude could lead to reduction of false positives and increase of PPV in Br(E)
      MsEP monitoring. LEVEL OF EVIDENCE: 3.

PMID- 30106391
TI  - A spatio-temporal land use and land cover reconstruction for India from 1960
      2010.
AB  - In recent decades India has undergone substantial land use/land cover change as a
      result of population growth and economic development. Historical land use/land
      cover maps are necessary to quantify the impact of change at global and regional
      scales, improve predictions about the quantity and location of future change and
      support planning decisions. Here, a regional land use change model driven by
      district-level inventory data is used to generate an annual time series of high
      resolution gridded land use/land cover maps for the Indian subcontinent between
      1960-2010. The allocation procedure is based on statistical analysis of the
      relationship between contemporary land use/land cover and various spatially
      explicit covariates. A comparison of the simulated map for 1985 against remotely
      sensed land use/land cover maps for 1985 and 2005 reveals considerable
      discrepancy between the simulated and remote sensing maps, much of which arises
      due to differences in the amount of land use/land cover change between the
      inventory data and the remote sensing maps.

PMID- 30106390
TI  - One millennium of historical freshwater fish occurrence data for Portuguese
      rivers and streams.
AB  - The insights that historical evidence of human presence and man-made documents
      provide are unique. For example, using historical data may be critical to
      adequately understand the ecological requirements of species. However, historical
      information about freshwater species distribution remains largely a knowledge
      gap. In this Data Descriptor, we present the Portuguese Historical Fish Database
      (PHish-DB), a compilation of 2214 records (557 at the basin scale, 184 at the sub
      basin scale and 1473 at the segment scale) resulting from a survey of 194
      historical documents. The database was developed using a three-scale approach
      that maximises the inclusion of information by allowing different degrees of
      spatial acuity. PHish database contains records of 25 taxonomical groups and
      covers a time span of one millennium, from the 11th until the 20th century. This
      database has already proven useful for two scientific studies, and PHish further
      use will contribute to correctly assess the full range of conditions tolerated by
      species, by establishing adequate benchmark conditions, and/or to improve
      existing knowledge of the species distribution limits.

PMID- 30106392
TI  - The HAM10000 dataset, a large collection of multi-source dermatoscopic images of
      common pigmented skin lesions.
AB  - Training of neural networks for automated diagnosis of pigmented skin lesions is
      hampered by the small size and lack of diversity of available datasets of
      dermatoscopic images. We tackle this problem by releasing the HAM10000 ("Human
      Against Machine with 10000 training images") dataset. We collected dermatoscopic
      images from different populations acquired and stored by different modalities.
      Given this diversity we had to apply different acquisition and cleaning methods
      and developed semi-automatic workflows utilizing specifically trained neural
      networks. The final dataset consists of 10015 dermatoscopic images which are
      released as a training set for academic machine learning purposes and are
      publicly available through the ISIC archive. This benchmark dataset can be used
      for machine learning and for comparisons with human experts. Cases include a
      representative collection of all important diagnostic categories in the realm of
      pigmented lesions. More than 50% of lesions have been confirmed by pathology,
      while the ground truth for the rest of the cases was either follow-up, expert
      consensus, or confirmation by in-vivo confocal microscopy.

PMID- 30106393
TI  - A chemical, crystallographic and magnetic characterisation of individual iron
      oxide grains in Hawaiian lavas.
AB  - Our knowledge on the behaviour of the geomagnetic field through time critically
      depends on how information of the past state of the field is recorded by, and
      stored in iron-bearing minerals such as magnetite. For small, single domain
      grains these processes are described by classical Neel theory, but the magnetic
      behaviour of larger, pseudo-single domain or multidomain grains, still is
      enigmatic. Here we present a chemical, crystallographic and magnetic
      characterisation of three to six individual, large (~3-10 MUm) iron-oxide grains
      from eleven different flows sampled on the Big Island of Hawai'i. These grains
      were all subjected to a Magnetic Force Microscopy study to characterise their
      magnetic domain structure; a Microprobe analyses to assess their chemical
      composition; and a Scanning Electron Microscopy study to identify phases and
      crystallographic orientations. This comprehensive dataset enables systematic
      analyses of their magnetic behaviour as function of chemistry and forms the basis
      for future micromagnetic modelling studies eventually contributing to the
      development of a fundamental theory of magnetic behaviour in large iron-oxide
      grains.

PMID- 30106394
TI  - The REMBRANDT study, a large collection of genomic data from brain cancer
      patients.
AB  - The Rembrandt brain cancer dataset includes 671 patients collected from 14
      contributing institutions from 2004-2006. It is accessible for conducting
      clinical translational research using the open access Georgetown Database of
      Cancer (G-DOC) platform. In addition, the raw and processed genomics and
      transcriptomics data have also been made available via the public NCBI GEO
      repository as a super series GSE108476. Such combined datasets would provide
      researchers with a unique opportunity to conduct integrative analysis of gene
      expression and copy number changes in patients alongside clinical outcomes
      (overall survival) using this large brain cancer study.

PMID- 30106395
TI  - Effect of Different Cavity Lining Techniques on Marginal Sealing of Class II
      Resin Composite Restorations In Vitro.
AB  - This study investigated the effect of different cavity lining techniques on the
      marginal sealing of Class II composite restorations. A total of 36 human molar
      teeth, free of caries and fillings, were each prepared with two proximal Class II
      boxes mesially and distally. In mesial boxes, cavity liners were applied as
      follows: in group 1, separately cured flowable composite; in group 2, co-cured
      flowable composite; and in group 3, resin-modified glass ionomer (RMGI). The
      remaining cavities were filled incrementally with a universal restorative
      composite. The distal boxes were filled with no liner as controls. After
      thermocycling, the specimens were immersed in a silver nitrate solution and the
      microleakage was evaluated. Analysis of variance showed that the degree of
      microleakage for group 3 was significantly lower than that of the other groups.
      Based on the results, it was concluded that the use of RMGI as a cavity liner
      under composite restorations showed the least microleakage. Flowable composites,
      whether co-cured or separately cured, had no influence on the marginal sealing.

PMID- 30106397
TI  - An S-alkyl thiocarbamate-based biosensor for highly sensitive and selective
      detection of hypochlorous acid.
AB  - We reported a near-infrared biosensor that features a dihydromethylene blue and
      an S-alkyl thiocarbamate linker to detect hypochlorous acid in a drastic
      fluorescence turn-on response. We achieved high sensitivity at the nanomolar
      level and high selectivity that resolves the interference issue with mercury ions
      and other transition metal ions. We demonstrated the response mechanism by
      analysing the released segments, and investigated the imaging capability to
      detect both exogenous and endogenous hypochlorous acid in living cells.

PMID- 30106396
TI  - A comparative study of dissolving hyaluronic acid microneedles with trehalose and
      poly(vinyl pyrrolidone) for efficient peptide drug delivery.
AB  - We studied the role of the additives trehalose and poly(vinyl pyrrolidone) in the
      physical and pharmacokinetic properties of peptide drug incorporated hyaluronic
      acid microneedles. Poly(vinyl pyrrolidone) increases the mechanical strength of
      microneedles and ameliorates drug bioavailability in vivo, suggesting that
      poly(vinyl pyrrolidone) can be a promising additive in the fabrication of peptide
      drug-encapsulated fully dissolving microneedles.

PMID- 30106398
TI  - Engineering a cleavable disulfide bond into a natural product siderophore using
      precursor-directed biosynthesis.
AB  - An analogue of the bacterial siderophore desferrioxamine B (DFOB) containing a
      disulfide motif in the backbone was produced from Streptomyces pilosus cultures
      supplemented with cystamine. Cystamine competed against native 1,5-diaminopentane
      during assembly. DFOB-(SS)1[001] and its complexes with Fe(iii) or Ga(iii) were
      cleaved upon incubation with dithiothreitol. Compounds such as DFOB-(SS)1[001]
      and its thiol-containing cleavage products could expand antibiotic strategies and
      Au-S-based nanotechnologies.

PMID- 30106399
TI  - Noble-metal-free Ni3N/g-C3N4 photocatalysts with enhanced hydrogen production
      under visible light irradiation.
AB  - The majority of visible-light photocatalysts show very low hydrogen evolution
      activity in the absence of noble metal co-catalysts due to their fast carrier
      recombination rate. Metallic interstitial nitrides have been recognized as
      excellent hydrogen evolution electrocatalysts and therefore are promising
      alternative co-catalysts for photocatalytic hydrogen production. Herein we report
      a low-cost, efficient, noble-metal-free visible-light-driven hydrogen evolution
      photocatalyst composed of Ni3N/g-C3N4 heterostructures. The as-prepared
      photocatalyst with a Ni3N loading content of 3 wt% shows a high hydrogen
      evolution rate of 169 MUmol g-1 h-1, which is slightly higher than that of 3 wt%
      Pt modified g-C3N4 (152.0 MUmol g-1 h-1). The Ni3N/g-C3N4 photocatalysts also
      exhibit remarkable photostability for four consecutive cycles of photocatalytic
      activity tests with a total reaction time of 12 hours. The excellent performance
      of the Ni3N/g-C3N4 photocatalyst is ascribed to the formation of an optimal
      number of Ni3N/g-C3N4 heterojunctions that improve photogenerated carrier
      separation and offer abundant photocatalytically active sites for surface
      reactions.

PMID- 30106402
TI  - Molecular tweezers with a rotationally restricted linker and freely rotating
      porphyrin moieties.
AB  - The effect of the degree of conformational rigidity and/or flexibility on
      preorganisation in artificial molecular receptors continues to be actively
      explored by supramolecular chemists. This work describes a bis-porphyrin
      architecture, linked via a rigid polycyclic backbone, in which a sterically bulky
      2,3,5,6-tetramethylphenyl diimide core restricts rotation to afford two non
      interconvertible tweezer conformations; syn- and anti-. After separation, the
      host-guest chemistry of each conformation was studied independently. The
      difference in host geometry allows only the syn-conformation to form a strong 1 :
      1 bis-porphyrin complex with the diamino ligand 1,4-diazabicyclo[2.2.2]octane
      (DABCO) (K11 = 1.25 * 108 M-1), with the anti-conformation adopting a 2 : 2
      sandwich complex with DABCO (K22 = 5.57 * 1017 M-3).

PMID- 30106404
TI  - One step fabrication of novel Ag-CdS@EP floating photocatalyst for efficient
      degradation of organic pollutants under visible light illumination.
AB  - In this paper, we present the fabrication of an expanded-perlite (EP)-based
      floating photocatalyst comprising CdS and Ag nanoparticles. In the Ag-CdS/EP
      nanocomposite, Ag-CdS was introduced as the photocatalytically active components
      and EP was employed as a low cost and sustainable support to reduce the problem
      of easy aggregation and improve the floating behavior of the designed catalyst.
      The Ag-CdS/EP photocatalyst was characterized via transmission electron
      microscopy (TEM), high-resolution transmission electron microscopy (HR-TEM),
      scanning electron microscopy (SEM), X-ray diffraction (XRD), UV-vis diffuse
      spectroscopy (UV-vis DRS), energy dispersive spectroscopy (EDS), X-ray
      photoelectron spectroscopy (XPS), and photoluminescence (PL) and
      photoelectrochemical measurements. The XRD and HR-TEM results confirmed the
      formation of cubic crystalline silver nanoparticles anchored on the surface of EP
      immobilized hexagonal cubic CdS. The significantly enhanced photocatalytic
      activities of the Ag-CdS/EP nanocomposite with varying Ag contents were
      investigated for the degradation of rhodamine B (RhB) and phenol under visible
      light irradiation, and it was found that the photocatalytic reaction proceeds via
      first order kinetics. Furthermore, the desirable cycling ability (5 runs) of the
      Ag-CdS/EP photocatalyst indicates its promising stability and reusability. The
      designed novel photocatalyst also conforms to the development of green chemistry
      since no organic solvents were required.

PMID- 30106408
TI  - High efficiency green OLEDs based on homoleptic iridium complexes with steric
      phenylpyridazine ligands.
AB  - A series of steric phenylpyridazine based homoleptic iridium(iii) complexes (1-3)
      have been synthesized with novel one-pot methods. Single X-ray structural
      analyses are conducted on complexes 1 and 2 to reveal their coordination
      arrangement. These complexes exhibit a very strong green phosphorescence emission
      with high quantum yields of over 64%. The relationship between photophysical
      properties and the substituent nature of the complexes is discussed by density
      functional theory (DFT) and time-dependent DFT. Self-quenching is significantly
      reduced for these complexes in solid even at very high concentrations because the
      sterically hindered bicyclo [2.2.2] oct-2-ene and m-substituted CF3 spacers in
      the phosphor molecules lead to minimum bimolecular interactions. Accordingly, the
      electroluminescence device based on complex 3 exhibits a maximum luminous
      efficiency of 64.1 cd A-1 with a high EQE of 25.2% at a high doping concentration
      of 15 wt%. Meanwhile, when neat 3 was adopted as the emitting layer, the non
      doped green device gives a state-of-the-art EQE as high as 15.2% (40.1 cd A-1)
      along with CIE coordinates of (0.346, 0.599).

PMID- 30106407
TI  - White light emitting MgAl2O4:Dy3+,Eu3+ nanophosphor for multifunctional
      applications.
AB  - Feeble white emission with a low Colour Rendering Index (CRI) has become the
      principal gridlock for the extensive commercialization of phosphor converted
      white LEDs (pc-WLEDs). Fusion of red, green and blue emitting rare-earth (RE)
      ions in a suitable host can overcome these drawbacks but the energy migration
      between multiple RE ions at single excitation wavelength defines the key
      standpoint in designing such white light emitting phosphors. Apart from the
      abovementioned obstacles, recently traditional optical temperature sensors based
      on RE ions have faced difficulties due to their low relative sensitivity and
      large detection error. Keeping these points in mind, in this work, a series of
      MgAl2O4:Dy3+,Eu3+ nanophosphors are synthesized among which 2% Dy3+,0.2% Eu3+
      doped MgAl2O4 nanophosphors demonstrate strong white emission with CIE co
      ordinates of (0.31, 0.33), and high quantum yield (~67%), which could be directly
      utilized for pc-WLED based solid state lighting devices. Detailed investigation
      of PL properties reveals that Eu3+ ions can be well sensitized by Dy3+ under near
      ultraviolet excitation of 351 nm. Dexter's theory & Reisfeld's approximation are
      employed for an in-depth analysis of the inter-RE energy transfer (ET) mechanism,
      which signposts that the dipole-quadrupole interaction phenomenon is responsible
      for the ET process from Dy3+ to Eu3+. Additionally, the validated ET plays a
      pivotal role in demonstrating the self-referencing ratiometric temperature sensor
      behaviour supported by a distinct high temperature thermal quenching trend
      between Dy3+ and Eu3+ ions. Hence the obtained nanophosphors are highly promising
      for utilizing in WLED based solid state lighting and self-referencing ratiometric
      temperature sensor applications.

PMID- 30106409
TI  - Hydrogen storage on volleyballene.
AB  - This study is devoted to the hydrogenation of the recently predicted
      volleyballene (Sc20C60) compound. The hydrogenation produces structures with 24
      and 70 H atoms, respectively. Twelve of the 20 available Sc atoms and C5 rings
      are found as preferred sites for hydrogenation. DFT calculations attest a H2
      uptake capacity of 4.20 wt% for the heavily hydrogenated structure (Sc20C60H70),
      and a corrected -0.11 eV/H2 adsorption energy value. Calculated entalphy
      (negative) and entropy (positive) values assure that the hydrogenation reaction
      of volleyballene can be achieved at ambient temperature. The heavily hydrogenated
      structure holds a 1.1 eV HOMO-LUMO gap value and it does not feature imaginary
      frequencies attesting its experimental convenience.

PMID- 30106410
TI  - Nanoscale mechanics of microgel particles.
AB  - Microgel particles are highly tuneable materials that are useful for a wide range
      of industrial applications, such as drug delivery, sensing, nanoactuation,
      emulsion stabilisation and use as cell substrates. Microgels have also been used
      as model systems investigating physical phenomena such as crystallization, glass
      formation, jamming, ageing and complex flow behaviour. The responsiveness of
      microgel systems such as poly(N-isopropylacrylamide) (PNIPAm) to external stimuli
      has been established in fundamental investigations and in applications and recent
      work has begun to quantify the mechanics of individual particles. However little
      focus has been placed on determining their internal mechanical properties, which
      is likely to relate to their nonuniform internal structure. In this work we
      combine atomic force microscopy, force spectroscopy and dynamic light scattering
      to mechanically profile the internal structure of microgel particles in the size
      range of ~100 nm, which is commonly used both in practical applications and in
      fundamental studies. Nanoindentation using thermally stable cantilevers allows us
      to determine the particle moduli and the deformation profiles during particle
      compression with increasing force, while peak force nanomechanical mapping (PF
      QNM) AFM is used to capture high resolution images of the particles' mechanical
      response. Combining these approaches with dynamic light scattering allows a
      quantitative profile of the particles' internal elastic response to be
      determined. Our results provide clear evidence for a radial distribution in
      particle mechanical response with a softer outer "corona" and a stiffer particle
      core. We determine the particle moduli in the core and corona, using different
      force microscopy approaches, and find them to vary systematically both in the
      core (~17-50 kPa) and at the outer periphery of the particles (~3-40 kPa).
      Importantly, we find that highly crosslinked particles have equivalent moduli
      across their radial profile, reflecting their significantly lower radial
      heterogeneity. This ability to accurately and precisely probe microgel radial
      profiles has clear implications both for fundamental science and for industrial
      applications.

PMID- 30106411
TI  - Computational mechanistic elucidation of the rare earth metal-mediated
      cycloamidination of aminoalkenes with nitriles.
AB  - A detailed computational probe of the rare earth metal-mediated intramolecular
      amidination of aminoalkenes with nitriles by an archetypical [Y{N(SiMe3)2}3]
      precatalyst is presented. The mechanistic picture derived from smooth energy
      profiles, acquired by employing a reliable computational protocol applied to a
      realistic catalyst model, conforms to available experimental data that includes a
      significant primary KIE. Sequential Y-N silylamide aminolysis transforms the
      precatalyst into a multitude of silylamide/amide compounds, of which the bis
      amine coordinated [Y{N(SiMe3)2}(NRR')2] is the most abundant, capable of
      promoting cycloamidination. Nitrile insertion is irreversible and readily
      furnishes the kappa2-N-amidinate yttrium intermediate, which readily rearranges
      into more stable isomers featuring kappa2-N,Delta and kappa1-N(imine) amidinate
      ligations. Its bis-amine adduct likely represents the catalyst resting state. The
      alkenylamidine becomes accessible through kinetically affordable Y-N amidinate
      bond protonolysis, which can best be viewed as a kinetically mobile equilibrium
      that favours the amidinate. The generation of 2-imidazoline product via N-C bond
      forming amidinate cyclisation favours a stepwise sigma-insertive cyclisation/Y-C
      alkyl aminolysis sequence over an otherwise kinetically prohibitive proton
      triggered concerted N-C/C-H bond forming process. The operative sigma-insertive
      pathway entails reversible olefin 1,2-insertion followed by turnover-limiting Y-C
      alkyl aminolysis at the short-lived 4-imidazolylalkyl intermediate. The DFT
      estimated primary KIE associated with aminolysis is gratifyingly close to the
      observed value, thereby supporting the derived mechanistic view.

PMID- 30106413
TI  - Epidemiological evaluation of an Acinetobacter baumannii outbreak observed at an
      intensive care unit.
AB  - OBJECTIVES: To reveal the relationship between clinical and environmental
      isolates, analyzing both phenotypic and molecular aspects, in an Acinetobacter
      baumannii (A. baumannii) epidemic, and to use the epidemiological data to
      determine the source of the epidemic, to identify potential risk factors, and
      inform the effort to prevent and manage future epidemics. METHODS: Acinetobacter
      baumannii was isolated from 5 clinical samples in Sultan Abdulhamid Han Training
      and Research hospital, Istanbul, Turkey, for a week period. To determine
      potential sources of infection we established  cultures surveillance.
      Microbiological identification and antibiotic susceptibility testing of A.
      baumannii were performed using conventional methods and automated identification
      system. Multiplex polymerase chain reaction (PCR) and pulsed-field gel
      electrophoresis (PFGE) were used for carbapenemase gene screening and clonal
      relationship evaluation. RESULTS: Among the environmental samples, bacterial
      growth was observed in 3 of the sample cultures. Clinical and environmental
      samples collected from patients X and Y had phenotypically similar antibiotic
      susceptibility patterns. The clinical and environmental isolates from patients X
      and Y comprised the first cluster (6 isolates), the isolates from patient Z
      formed the second cluster (2 isolates). CONCLUSION: We detected that all outbreak
      related isolates contained the same OXA-type carbapenemase genes. Phenotypic
      similarity, based on the analysis of antimicrobial susceptibility patterns, was
      correlated with genotypic similarity. These results suggest that monitoring
      antimicrobial resistance patterns with daily culture surveillance follow-ups,
      coupled with the use of amplification based methods to detect that clonal
      relationships are important for the early identification of outbreaks and rapid
      deployment of proper countermeasures to halt the spread of the causative agent.

PMID- 30106414
TI  - Impact of cyclooxygenase-2 over-expression on the prognosis of colorectal cancer
      patients. An experience from Western Saudi Arabia.
AB  - OBJECTIVES: To evaluate cyclooxygenase-2 (COX-2) over-expression in colorectal
      cancer (CRC) and its role in carcinogenesis and prognosis. METHODS: It was a
      retrospective study. Archival samples were obtained from Pathology Department at
      King Fahad Hospital, Madinah, Saudi Arabia, over 11 years' period (January 2006
      to December 2017). Samples were analyzed using immunohistochemistry for COX-2 and
      Ki67 over-expression in 324 CRC patients, 40 cases of colorectal adenomas and 20
      cases of normal colonic mucosa. RESULTS: Cyclooxygenase-2 over-expression was
      observed in 40% of normal colonic mucosa, 65% of colorectal adenoma and 84.6% of
      CRC cases. There were no significant correlations between COX-2 over-expression
      and age, gender, tumor site, or tumor size. However, COX-2 over-expression
      revealed highly significant correlations with tumor differentiation, lymph node
      metastasis, lympho-vascular invasion, distant metastasis, advanced stages, and
      high Ki67 expression. Univariate Kaplan-Meir survival analysis showed that
      patients with high COX-2 expression had significantly shorter periods of
      survival. Multivariate analysis by means of the COX-2 regression model revealed
      that high COX-2 over-expression, AJCC, and Ki67 expression were the only
      significant independent prognostic indicators. CONCLUSION: Cyclooxygenase-2 over
      expression increases during normal-adenoma-carcinoma sequence, moreover COX-2
      over-expression is associated with advanced tumor stage and Ki67 over-expression.
      These findings suggest a significant role of COX-2 in the carcinogenesis and
      prognosis of CRC in our study population.

PMID- 30106412
TI  - Circulating rotavirus G and P strains post rotavirus vaccination in Eastern
      Mediterranean Region.
AB  - OBJECTIVE: To detect changes in circulating strains of rotavirus in the Eastern
      Mediterranean Region post rotavirus immunization drive. METHODS: We searched
      MEDLINE, PubMed, ScienceDirect, and the Cochrane Library and specific database
      website (Nutrition and Food Sciences) for relevant articles. Our search included
      websites of a number of relevant organizations in addition to gray literature
      search. Of the 2198 articles found, we included only 35 studies after excluding
      irrelevant, ineligible, duplicated, and very low-quality papers. RESULTS: Thirty
      pre-vaccination studies reported frequent rotavirus strains among children below
      5 years of age. G1P[8] has been identified as the most dominant type prior to
      vaccination in Eastern Mediterranean Region (EMR) countries. Five post
      vaccination studies conducted in 3 countries (Saudi Arabia, Morocco, and Yemen)
      illustrated that G1P[8] is the most prevalent strain in Saudi Arabia, and the
      incidence of G2P[4] has increased from 21.6% to 33.3%. In Yemen, G1P[4] is the
      most prevalent strain (87.5%), followed by G9P[8] (57%) and G1P[8] (18.5%).
      Furthermore, in Yemen, G9P[8] were the most prevalent strains accounting to 57%
      and 14% in G9P[4], post vaccination. Finally, in Morocco, G1P[8] was not reported
      3 years post vaccination; however, incidence of G9P[8] was reported at 67% and
      G2P[4] at 33%. CONCLUSIONS: Rotavirus circulating strain prevalence in EMR
      countries has changed post vaccination, and G9P[8], G2P[4], and G9P[4] have
      become more dominant. Proportion of rotavirus strains in these countries after
      vaccination has significantly reduced. There is an increase in circulating strain
      G2P[4] in the post-vaccination period, which needs further monitoring.

PMID- 30106415
TI  - Coronary artery bypass surgery in Syrian refugees. Outcomes in a Turkish tertiary
      center.
AB  - OBJECTIVE: To assess  outcomes of Syrian refugees undergoing coronary artery
      bypass surgery in a tertiary hospital in Turkey. METHODS:  We sought for in
      hospital mortality and one year all-cause mortality as the main outcomes. We
      reviewed records of 67 Syrian and 427 Turkish patients undergoing isolated
      coronary bypass surgery between 2015 January and 2017 January retrospectively. 
      Results: History of coronary, peripheral and carotid artery diseases and obesity
      were more frequent in Syrian patients. C-reactive protein levels were  higher in
      Syrian patients whereas lipid profiles and systolic functions of the 2 groups
      were similar. Syrian patients more frequently presented with the acute coronary
      syndrome (26.9% versus 15.5%, p<0.001).  SYNTAX I (Synergy between PCI with Taxus
      and Cardiac Surgery) and SYNTAX II-PCI were higher in Syrian patients whereas
      SYNTAX II-CABG  was similar with Turkish patients. Extubation time was longer and
      amount of the hemorrhage was greater in Syrian patients; however, bleeding
      revision was not increased. Although wound infection was more frequent in Syrian
      patients, postoperative complications were similar between groups. In-hospital
      mortality and one year all-cause mortality did not differ between Syrian (n=1;
      1.5% versus n=13; 13.1%) (p=0.476) and Turkish patients (n=3; 4.5% versus n=25;
      5.9%) (p=0.63). CONCLUSION: Syrian patients had higher SYNTAX I and SYNTAX II PCI
      scores, but not SYNTAX II CABG score compared with Turkish patients.
      Intraoperative and postoperative complications were similar. In-hospital
      mortality and one year all-cause mortality of Syrian patients were similar with
      Turkish patients. Surgical outcomes of Syrian patients were acceptable. Primary
      prevention of obesity must be provided. Aggressive secondary preventive measures
      must be taken due to increased severity of coronary artery disease.

PMID- 30106416
TI  - Efficacy and safety of endoscopic dilatation in the management of esophageal
      strictures in children.
AB  - OBJECTIVES: To determine the outcomes  of endoscopic dilatation of esophageal
      strictures in children. METHODS: Children younger than 18 years of age diagnosed
      with esophageal strictures over a period of 7 years (June 2010 to June 2017) were
      reviewed and analyzed retrospectively. The study took place at King Khalid
      University Hospital, Riyadh, Saudi Arabia. The patients' clinical
      characteristics, endoscopic findings, and details of the strictures, treatment,
      and outcomes were documented. RESULTS: Forty-three children with esophageal
      strictures were identified (median age, 8.1 years; range, 2-17 years; 23 [53.5%]
      boys). The median age at presentation was 2 years (range, 1-16 years), and the
      median follow-up period was 3 years (range, one month-17 years).
      Tracheoesophageal fistula (n=14, 32.6%), gastroesophageal reflux disease (n=10,
      23.3%) and eosinophilic esophagitis (n=8, 18.6%) were the leading causes of
      esophageal strictures. Forty-three patients underwent 180 dilatation sessions;
      the median number of dilatation sessions per patient was 3 (range, 1-48), and the
      median interval between sessions was 8 weeks (range, 1-24 weeks). Among 180
      dilatation sessions, 3 events (1.7%) of esophageal perforation were observed. The
      outcomes varied depending on the primary cause of the stricture; complete
      response was achieved the best in eosinophilic esophagitis-related strictures
      (87.5%), followed by anastomotic strictures post tracheoesophageal fistula repair
      (71.4%) and gastroesophageal reflux disease-related strictures (70%). CONCLUSION:
      Endoscopic dilatation is a safe and effective intervention in the management of
      esophageal strictures in children, with minimal complications when conducted by
      experts.

PMID- 30106417
TI  - The association between the prevalence of restless leg syndrome, fatigue, and
      sleep quality in patients undergoing hemodialysis.
AB  - OBJECTIVE: To determine the prevalence of restless legs syndrome (RLS) in
      patients with chronic renal failure (CRF) and to compare CRF patients with or
      without RLS in terms fatigue and sleep quality. METHODS: A cross-sectional study
      was conducted on 220 patients (18-75 years) who were undergoing dialysis 3 times
      weekly in Corum Province, Corum, Turkey, between January 2014 and January 2016.
      The diagnosis of RLS was based on the diagnostic form proposed by the
      international RLS study group. Sleep quality was evaluated using the Pittsburgh
      sleep quality index (PSQI), and severity of fatigue was determined by using
      fatigue severity scale (FSS). RESULTS: Of all the participants, 16.8% (n= 37)
      (Group 1) were found to have RLS, while 183 patients had no RLS (Group 2). The
      mean ages were similar between groups. With respect to laboratory analyses, a p
      value of less than 0.05 was considered in Group 1 than in Group 2. Restless legs
      syndrome was mild (7.1%), moderate (46.4%) and severe (39.3%) in patients with
      RLS. Factors associated with the severity of RLS included weight, duration of
      dialysis, anuria, iron, total iron binding capacity, calcium and transferrin
      saturation. The PSQI and FSS scores were significantly worse in Group 1 (p less
      than 0.001). CONCLUSION: Restless legs syndrome is a common condition in patients
      undergoing hemodialysis; the results of our study confirm the adverse effects of
      RLS in terms of many aspects of sleep quality and fatigue.

PMID- 30106418
TI  - Factors affecting quality of life in children and adolescents with thalassemia in
      Iraqi Kurdistan.
AB  - OBJECTIVES: To assess the health related quality of life (HRQoL) in Iraqi Kurd
      children and adolescents with thalassemia, and identify the factors that affect
      it. METHODS:  In the period between May and June 2018, 100 thalassemic patients
      and 100 healthy subjects between the ages of 6-18 years were enrolled. The
      patients included 73 with thalassemia major (TM) and 27 with intermedia (TI).
      Patients were clinically re-evaluated, and the pediatric quality of life
      inventory (PedsQL) 4.0 was administered by both child and parent reports.
      Results: The mean HRQoL score of thalassemic patients was significantly lower
      than that of healthy subjects, with lowest scores in physical functioning.
      Furthermore, the mean HRQoL of TM was significantly lower than that of TI
      subgroup. Significantly lower mean HRQoL scores were seen in those taking >=6
      transfusions/year, with hepatitis C infection, with illiterate parents, and those
      on oral iron chelation. Pearson correlation revealed that HRQoL was negatively
      associated with age, frequency of transfusions, and serum ferritin, but
      positively correlated with age at starting transfusion and age at diagnosis. Only
      age and serum ferritin remained significant by multivariate analysis. CONCLUSION:
      This study shows that among Iraqi Kurds with thalassemia, the disease has a
      significant negative impact on quality of life, with age and serum ferritin being
      identified as independent predictors.  Psychosocial, educational, and patient
      centered management programs may be needed to improve HRQoL in this disease.

PMID- 30106419
TI  - Sociodemographic, environmental and lifestyle risk factors for multiple sclerosis
      development in the Western region of Saudi Arabia. A matched case control study.
AB  - OBJECTIVES: To examine the association of exposure to sociodemographic,
      environmental, and lifestyle risk factors during adolescence with the development
      of multiple sclerosis (MS). METHODS: We conducted a case-control study between
      October 2017 and January 2018 at King Fahd General Hospital (KFH) in Madinah,
      Saudi Arabia. Data were collected by direct physician-subject interviews. We
      utilized a questionnaire modified from the environmental risk factors in multiple
      sclerosis questionnaire (EnvIMS-Q). Chi-square tests were used to examine
      associations of selected risk factors with the development of MS, a p-value of
      less than 0.05 was considered significant. RESULTS: A total of 80 cases and 160
      controls were enrolled into the study. Smoking during adolescence significantly
      increased the risk of MS, with an adjusted odds ratio (AOR) of 4.165, and a 95%
      confidence interval (CI) of 1.449-11.974. Large body size, assessed using a
      figure rating scale, also increased the risk of MS (AOR=8.970, 95% CI=1.032
      77.983), as well as a history of measles infection (AOR=3.758, 95% CI=1.455
      9.706). Furthermore, exposure to sunlight during the weekend for more than 4
      hours/day decreased the risk of MS (AOR=0.063, 95% CI=0.006-0.654), so did the
      consumption of fish for more than once per week (AOR=0.206, 95% CI=0.055-0.773). 
      Conclusion: The risk of developing MS is significantly increased by exposure
      during adolescence to smoking, a history of measles infection, and large body
      size (obesity).

PMID- 30106420
TI  - Effects of facemask therapy on the mandibular retromolar space. A follow-up
      study.
AB  - OBJECTIVES: To evaluate the mandibular retromolar space after facemask therapy
      and a follow-up period.  Methods: This retrospective study was conducted between
      May and September in 2014. The sample consisted of pre-treatment (T1), post
      treatment (T2), and follow-up(T3) panoramic radiographs of 19 skeletal and dental
      Class III patients (7 female, 12 male; mean age: 10.5 years) treated with
      facemask and a removable intraoral upper appliance in the Faculty of Dentistry
      Gazi University, Ankara, Turkey. Each patient's lower arches were evaluated as
      right and left segments. As third molars were congenitally absent in 3 segments,
      a total of 35 segments were evaluated. The average treatment time was one year.
      The average follow-up period was 2.4 years. The positions, angulations, dental
      maturations of lower third molars, and mandibular retromolar spaces (DJ) were
      assessed. Friedman's 2-way Analysis of Variance, multiple-comparison, Pearson's
      correlation, and Chi-square tests were used for statistical evaluation. A p less
      than 0.05 was considered as significant. RESULTS: The angulation of the first
      molar (Upsilon) increased significantly only in the follow-up period (T3).
      Mandibular retromolar spaces were increased significantly during all periods. The
      most commonly determined position of the third molar, by Winter's classification,
      was vertical angulation in all periods. Moderate and significant correlations
      were found between third molar angulation(beta) and DJ at T2 and T3. Significant
      correlations were also found between DJ and Demirjian classification stages
      during all periods. CONCLUSION: Facemask therapy did not have an adverse effect
      on the mandibular retromolar space during treatment and follow up periods.

PMID- 30106421
TI  - Orthodontic treatment needs in Saudi young adults and manpower requirements.
AB  - OBJECTIVES: To evaluate orthodontic treatment needs using the index of
      orthodontic treatment need (IOTN) components and to estimate the required
      manpower in the city of Jeddah, Saudi Arabia. METHODS: A cross-sectional study
      involving 670 participants (390 females and 280 males) collected between November
      2016 and April 2017, whose ages ranged from 12-19 years from secondary and high
      school students. Treatment needs were estimated using the IOTN components, dental
      health component (DHC), and aesthetic component (AC). RESULTS: The results
      according to the severity of malocclusion using IOTN-DHC found that 24.3% of the
      cases required severe/extreme need and 54.3% were in the no/slight need category.
      The most frequent types of malocclusion were crowding (48.8%) followed by
      increased overjet (21.8%), and spacing (16.1%). Using Pearson's Chi-squared test,
      there was a statistically significant association (p less than 0.001) between
      IOTN-DHC and IOTN-AC; 51.2% of the sample was in agreement at the mild need
      category, indicating a strong correlation, with a coefficient of 0.687.
      CONCLUSION: According to the IOTN's components, the present study showed that
      almost one-quarter of the sample had a severe/extreme need for orthodontic
      treatment. The most frequent type of malocclusion traits according to the
      severity was crowding followed by increased overjet and then spacing. The
      Ministry of Health must employ 90-110 orthodontists in Jeddah to meet the demands
      of the definite needs for orthodontics in adolescents.

PMID- 30106422
TI  - Bilateral adrenal hemorrhage in antiphospholipid syndrome. Anticoagulation for
      the treatment of hemorrhage.
AB  - A 43-year-old man with Hashimoto's thyroiditis and previous thromboembolic events
      treated with warfarin for 6 months, presented with right flank pain accompanied
      with vomiting, dizziness, and altered mental status 2 weeks after discontinuation
      of warfarin. His clinical examination findings were unremarkable. Routine blood
      work showed lymphopenia, thrombocytopenia, and hypoosmolar hyponatremia. Random
      serum cortisol level was low (14 nmol/L). Computed tomography scan of the abdomen
      revealed bilateral bulky heterogeneous suprarenal gland surrounded by fat
      stranding representing adrenal hemorrhage. He was treated for acute adrenal
      crisis and subsequently started on hydrocortisone and fludrocortisone, with
      significant clinical improvement. His diagnosis was secondary antiphospholipid
      syndrome (APS) to systemic lupus erythematosus (SLE). Bilateral adrenal
      thrombosis lead to hemorrhage in the adrenals as a paradoxical effect after
      warfarin cessation and primarily caused by APS. Bilateral adrenal bleeding should
      lead to the suspicion of thrombophilic disorders, such as APS, with cautious
      anticoagulation as the treatment of choice.

PMID- 30106423
TI  - Heterotopic pancreatic tissue in the gallbladder.
AB  - Heterotopic pancreas is defined as aberrantly located pancreatic tissue without
      anatomical, vascular, or neural connection to the pancreas. Usual sites include
      the stomach, duodenum, jejunum, and spleen; in rare cases, heterotopic pancreas
      can be found in the lungs, gallbladder, Meckel's diverticulum, and the
      mediastinum. In most cases, it is an insignificant, incidental finding. Pre
      operative diagnosis is not possible, and histopathological examination is
      mandatory for establishing a definite diagnosis. Less than 40 cases of
      heterotopic pancreas in the gallbladder have been reported worldwide. Recently, a
      laparoscopic cholecystectomy specimen from a 43-year-old male showed a small
      nodule in the gallbladder neck. Microscopy revealed heterotopic pancreas composed
      of exocrine and endocrine glandular tissue with ducts. We report this case to
      highlight this rare, incidental finding. This condition should not cause
      pathologists to over diagnose such occurrences as malignancies; neither should
      they be neglected because they have potential complications.

PMID- 30106424
TI  - Primary healthcare physicians' adherence to acute lower back pain referral
      guidelines in Riyadh, Saudi Arabia.
AB  - OBJECTIVES: To assess the primary healthcare physicians' adherence to referral
      guidelines for acute low back pain and if there is any association with
      experience level.  Methods: A cross-sectional study held in Tertiary care
      hospital, Riyadh, Kingdom of Saudi Arabia.Questionnaires were distributed in
      person between October 2017 and January 2018 among 100 primary healthcare
      physicians, with a 79% response rate. Results: The distribution between male to
      female was 43%-57%. Twenty-five percent of physicians encounter 1-5 patients
      weekly, while 28% encounter more than 15 patients. The physicians included had a
      higher than expected adherence to referral guidelines with percentages ranging
      between 63-94% referral rates for back pain related red flags. A trend was noted
      where there was an increase in referral decisions with increased experience when
      encountering red flags. More experienced physicians were more likely to refer
      when encountering; pain worse after prolonged sitting, limited mobility, and pain
      worse while coughing or sneezing (p less than 0.05). Conclusion: Primary
      healthcare physicians working in one health system in Riyadh had a higher than
      expected adherence to referral guidelines for back pain related red flags.

PMID- 30106425
TI  - Can hepatitis C virus be eliminated by 2030? Saudi Arabia as an example.
AB  - [No abstract available].

PMID- 30106426
TI  - Juvenile-onset systemic lupus erythematosus in Malay children.
AB  - [No abstract available].

PMID- 30106427
TI  - The role of C-peptide in the attenuation of outcomes of diabetic kidney disease:
      a systematic review and meta-analysis.
AB  - INTRODUCTION: Preclinical trials have shown that C-peptide may contribute to the
      treatment of diabetic kidney disease (DKD). This systematic review and meta
      analysis aimed to assess the use of C-peptide in attenuating the outcomes of DKD.
      METHODS: Searches were made on databases PubMed, Web of Science, and Scielo for
      in vivo clinical and preclinical trials written in English, Portuguese or Spanish
      that looked into the use of C-peptide in the attenuation of the outcomes of DKD.
      RESULTS: Twelve papers were included in this review, one clinical and eleven
      preclinical trials. In the clinical trial, DKD patients given C-peptide had lower
      levels of albuminuria than the subjects in the control group, but glomerular
      filtration rates were not significantly different. The main parameters assessed
      in the preclinical trials were glomerular filtration rate (six trials) and
      albuminuria (five trials); three trials described less hyperfiltration and three
      reported lower levels of albuminuria in the groups offered C-peptide. The meta
      analysis revealed that the animals given C-peptide had lower glomerular volumes
      and lower urine potassium levels than the groups not given C-peptide. CONCLUSION:
      The results of the studies included in the systematic review diverged. However,
      the meta-analysis showed that the animals given C-peptide had lower glomerular
      volumes and lower urine potassium levels.

PMID- 30106428
TI  - Perioperative factors associated with delayed graft function in renal transplant
      patients.
AB  - INTRODUCTION: Successful renal transplant and consequent good graft function
      depend on a good surgical technique, an anesthetic that ensures the hemodynamic
      stability of the receiver, and appropriate conditions of graft and recipient.
      Several factors can interfere with the perfusion of the graft and compromise its
      viability. The objective of this study was to evaluate perioperative factors
      associated with delayed graft function (DGF) in renal transplantation patients.
      METHODS: This is a historical cohort study of patients who underwent renal
      transplantation between 2011 and 2013. Three hundred and ten transplants were
      analyzed. DGF was defined as the need for dialysis during the first week post
      transplant. Logistic regression with a stepwise technique was used to build
      statistical models. RESULTS: Multivariate analysis revealed the following risk
      factor for DGF: combined anesthesia technique (OR = 3.81, 95%CI, 1.71 to 9.19), a
      fluid regimen < 50 mL.kg-1 (OR = 3.71, 95%CI, 1.68 to 8.61), dialysis for more
      than 60 months (OR = 4.77, 95%CI, 1.93 to 12.80), basiliximab (OR = 3.34, 95%CI,
      1.14 to 10.48), cold ischemia time > 12 hour (OR = 5.26, 95%CI, 2.62 to 11.31),
      living donor (OR = 0.19, 95%CI, 0.02 to 0.65), and early diuresis (OR = 0.02,
      95%CI, 0.008 to 0.059). The accuracy of this model was 92.6%, calculated using
      the area under the ROC curve. The incidence of DGF in the study population was
      76.1%. CONCLUSIONS: Combined anesthesia technique, dialysis for more than 60
      months, basiliximab, and cold ischemia time > 12 hours are risk factor for DGF,
      while liberal fluid regimens and kidneys from living donors are protective
      factors.

PMID- 30106429
TI  - Effect and mechanisms of celastrol on the apoptosis of HOS osteosarcoma cells.
AB  - Osteosarcoma is the most common primary malignant tumor of the bone found
      predominantly in children and teenagers and results in early metastasis and poor
      prognosis. The present study primarily focused on the impact of celastrol on
      apoptosis and autophagy of osteosarcoma HOS cells, as well as the related
      mechanisms. Following the appropriate treatment, the human osteosarcoma cell line
      HOS was assessed for viability, Ca2+ in cells, apoptosis and changes in cell
      morphology using Cell Counting Kit-8, flow cytometry, inverted phase contrast
      microscope, Hoechst staining and transmission electron microscopy. The expression
      levels of various proteins, including endoplasmic reticulum stress (ERS)-related
      proteins (Bip, PERK, p-PERK, IRE1alpha, calnexin, PDI and Erol-Lalpha), apoptosis
      related proteins (CHOP, cleaved caspase-12), mitochondrial apoptosis-related
      proteins (Bax, Bcl-2 and cytochrome c), cleaved caspase-3, and autophagy-related
      proteins (LC3-I, LC3-II and P62) and beta-actin, were assessed with western
      blotting. Celastrol significantly inhibited the viability of HOS cells in a dose
      dependent manner and promoted the expression of ERS-related, apoptosis-related
      and mitochondrial apoptosis-related proteins. The ERS inhibitor
      tauroursodeoxycholate promoted celastrol-induced autophagy and apoptosis of HOS
      cells. Pretreatment with the PERK inhibitor GSK2656157 significantly promoted
      celastrol-induced death and attenuated HOS cell autophagy. Our results indicated
      that the ERS pathway and the mitochondrial pathway were involved in celastrol
      induced apoptosis of HOS cells. The ERS/PERK pathway may protect HOS cells from
      apoptosis by celastrol and may play a complicated role in the process of
      autophagy.

PMID- 30106430
TI  - Impact of RNA-binding motif 3 expression on the whole transcriptome of prostate
      cancer cells: An RNA sequencing study.
AB  - RNA-binding motif 3 (RBM3) is a cold-shock protein that has been previously shown
      to attenuate cancer stem cell-like features in prostate cancer (PCa) cells.
      However, the mechanism underlying RBM3 regulation in PCa cells is largely
      unknown. The present study investigated the impact of RBM3 expression on the
      whole transcriptome of PCa cells using high-throughput RNA sequencing (RNA-seq).
      Differentially expressed genes (DEGs) that were identified through RNA-seq were
      applied to Gene Ontology (GO), pathway analysis, pathway-action networks and
      protein-protein interaction network analysis. GO and pathway ananlyses showed
      that RBM3 expression was associated with several metabolism pathways. Combining
      GO analysis and pathway analysis, certain DEGs, including phospholipase A2 group
      IIA (PLA2G2A), PLA2G2F, PLA2G4C, endothelin 1, cytochrome P450 family 2 subfamily
      B member 6, G protein subunit gamma5, nitric oxide synthase 3 and CD38 molecule,
      were shown to be closely associated with RBM3 regulation in PCa cells.
      Furthermore, the changes in expression of selected genes upon RBM3-knockdown in
      RNA-seq were confirmed by separate reverse transcription-quantitative-polymerase
      chain reaction, validating the results of RNA-seq. Thus, the present study
      provides a series of valuable reference genes and pathways for the future study
      of the pathogenic role of RBM3 in the development of PCa.

PMID- 30106431
TI  - alpha7-nAchR agonist GTS-21 reduces radiation-induced lung injury.
AB  - Radiation-induced lung injury (RILI) is a major complication of thoracic
      radiotherapy that starts as exudative inflammation and proceeds to lung fibrosis,
      and additional studies are required to develop methods to ameliorate RILI. The
      aim of this study was to explore whether the nicotinic acetylcholine receptor
      subtype-7 (alpha7-nAChR) agonist GTS-21 has a protective effect against RILI.
      C57BL6 mice were irradiated with 12 Gy to induce a mouse model of RILI. Some of
      the mice received an i.p. injection of 4 mg/kg GTS-21 for three days with or
      without radiation treatment. Mice were sacrificed at 1, 3, 7, 14 and 21 days and
      at 3 and 6 months after irradiation. The results showed that GTS-21 treatment
      significantly relieved RILI by decreasing TNF-alpha, IL-1beta and IL-6 production
      in serum via inhibition of NF-kappaB activation and downregulation of TLR-4 and
      HMGB1 expression in the lungs. In addition, we found that GTS-21 may regulate the
      MMP/TIMP balance in RILI. Finally, we found that GTS-21 inhibited NOX-1 and NOX-2
      expression, which subsequently reduced ROS levels and Hif-1alpha expression in
      RILI. However, GTS-21 showed little effect on lung tissue without radiation
      exposure. The results above were also validated in RAW264.7 macrophages. Our
      results showed that activation of the cholinergic anti-inflammatory pathway via
      the alpha7-nAChR agonist GTS-21 reduced RILI. The protective effect of GTS-21
      against RILI is partly attributed to inhibition of the HMGB1/TLR4/NF-kappaB
      pathway and ROS production. Thus, activation of the alpha7-nAChR pathway may lead
      to new possibilities in the therapeutic management of RILI.

PMID- 30106432
TI  - Netrin-1 induces the proliferation of gastric cancer cells via the ERK/MAPK
      signaling pathway and FAK activation.
AB  - Netrin-1 (NTN1) has been demonstrated to promote tumorigenesis in multiple types
      of cancer; however, its role in the growth of gastric cancer (GC) cells has not
      been described in detail. In the present study, the data suggested that NTN1
      knockdown significantly decreased the proliferation of GC cells, whereas NTN1
      overexpression had an opposing effect. Furthermore, the use of focal adhesion
      kinase (FAK) inhibitor decreased the proliferation of GC cells. It was also
      revealed that NTN1 markedly induced the phosphorylation of FAK, extracellular
      signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), but did not
      induce the phosphorylation of P38. In addition, the expression of ERK and JNK was
      markedly inhibited by treatment with FAK inhibitor. Xenograft analysis using GC
      cells revealed that NTN1 overexpression promoted tumor growth. Furthermore, the
      expression of NTN1 in samples collected from nude mice was downregulated in the
      NTN1 knockdown group and upregulated in the NTN1 overexpression group compared
      with the control short hairpin RNA group. These results suggest that NTN1-induced
      GC cell proliferation is mediated by activating ERK/MAPK signaling cascades via
      the distinct activation of FAK.

PMID- 30106433
TI  - Identification of the potential molecular mechanism and driving mutations in the
      pathogenesis of familial intestinal gastric cancer by whole exome sequencing.
AB  - The genetic alterations in familial intestinal gastric cancer (FIGC) have not
      been clearly understood. Aiming to explore the molecular basis and the driving
      mutations underlying the pathogenesis of FIGC, we performed exome sequencing of
      the blood samples of the members of an extended family with FIGC. The differences
      in mutation patterns between family members with gastric cancer and controls were
      analysed and the overlapped variants were screened by comparing previously
      published data for blood and tumours from gastric cancer patients. The overlapped
      genes harbouring insertions-deletions (INDELs) and single-nucleotide variants
      (SNVs) were subjected to function, pathway and network analysis. The INDELs were
      enriched in DNA packaging and in the neurological system process related to the
      biological process (BP), while SNVs were closely related to cell-function-related
      BPs. ESR was the significant node with marked centrality in the SNV network. ERK
      1/2 was the hub node in the INDEL network, interacting with EZK and IGF2R.
      Sequencing analysis revealed ESR1 homozygous mutations in exon 1 (216G > C) and
      exon 10 (2234C > T) and EZR1 heterozygous deletion of 68-69 GT nucleotides in
      exon 13 of the family members. The IGF2R gene only demonstrated a mutation in
      exon 48 of the propositus. All hub proteins had direct or indirect interactions
      in the protein-protein interaction network.

PMID- 30106434
TI  - Staurosporine alleviates cisplatin chemoresistance in human cancer cell models by
      suppressing the induction of SQSTM1/p62.
AB  - Cancer is one of the leading causes of mortality worldwide. Platinum-based
      chemotherapeutic agents such as cisplatin are the first line of treatment for
      many types of cancers. However, the development of cisplatin resistance after
      prolonged treatment is a common cause of cancer recurrence. In the present study,
      we investigated an approach designed to overcome resistance to cisplatin
      involving co-treatment with a second chemotherapeutic agent, staurosporine, and
      examined the role of sequestosome 1 (SQSTM1/p62) in enhancing cellular
      sensitivity to cisplatin. We utilized experimental models of three different
      cancers comprising cell lines derived from colon, breast, and ovarian tumors and
      investigated cell proliferation, morphology and p62 levels after treatment with
      cisplatin, staurosporine, or a combination of the two. Western blot analysis
      showed that cisplatin treatment resulted in elevation of p62 levels when compared
      to the corresponding control cells. Conversely, treatment with staurosporine
      resulted in a marked reduction in p62 levels in all three cell types and
      abrogated the cisplatin-induced upregulation of p62. These results suggest that
      staurosporine could sensitize cancer cells to cisplatin via a mechanism involving
      downregulation of p62.

PMID- 30106435
TI  - Sonodynamic therapy improves anti-tumor immune effect by increasing the
      infiltration of CD8+ T cells and altering tumor blood vessels in murine B16F10
      melanoma xenograft.
AB  - Sonodynamic therapy (SDT) uses a combination of sonosensitizers and low-intensity
      therapeutic ultrasound to destroy tumor cells. However, its effects on the tumor
      microenvironment, particularly on the immune state, remain unknown. The purpose
      of the present study was to examine the capacity and potency of the antitumor
      immunity induced by SDT. In the present study, sonosensitizer, 5-aminolevulinic
      acid (5-ALA), and/or ultrasound (US) were used to treat mouse B16F10 melanoma
      xenograft (1.0 MHz, 0.8 W/cm2, 10% duty cycle) and human umbilical vein
      endothelial cells (HUVECs; 0.87 MHz, 0.6 W/cm2, 60% duty cycle). Various immune
      cells, and proteins associated with the immunoregulation such as forkhead Box P3
      (Foxp3), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and CD80 were
      detected by immunofluorescence staining and western blotting. The effect of SDT
      on blood vessels which were located in the central and peripheral area of tumor
      tissues was observed by transmission electron microscopy, immunohistochemical and
      immunofluorescence staining. The effect of SDT on intercellular adhesion molecule
      1 (ICAM-1) expression on HUVECs was detected by western blotting and reverse
      transcription-semi-quantitative polymerase chain reaction. The results revealed
      that SDT inhibited tumor growth and improved outcomes. The mean inhibition rate
      of tumor volume in the US + ALA group was 43.8% and median survival was 45 days
      in US + ALA group vs. 27.5 days in the control group. SDT increased the number of
      CD45+ cells, in particular CD8+ and CD68+ cells and upregulated the expression of
      CD80 in the tumor tissues. The expression levels of Foxp3 and CTLA-4 were
      downregulated following SDT. The endothelial cells of tumor central were damaged,
      but the lumen area of the tumor peripheral vessels (TPVs) and the expression of
      ICAM-1 on HUVECs were increased after SDT. The results indicated that SDT
      improved the outcomes of melanoma-loading mice, increased the infiltration of
      CD8+ T cells and downregulates the expression of Foxp3 and CTLA-4 in mouse
      melanoma tissues. Furthermore, SDT increased the lumen area of TPVs in murine
      xenograft and the expression of ICAM-1 on HUVECs, which may be beneficial to the
      transendothelial migration of immune cells and the anti-tumor immune response.

PMID- 30106436
TI  - Decreasing O-GlcNAcylation affects the malignant transformation of MCF-7 cells
      via Hsp27 expression and its O-GlcNAc modification.
AB  - O-GlcNAcylation is a dynamic posttranslational modification of nucleoplasmic
      proteins. Previously, we reported that the O-GlcNAcylation level was increased in
      primary breast and colorectal cancer tissues. However, its precise roles in
      cancer development and progression are still largely unexplored. The aim of the
      present study was to investigate the roles of O-GlcNAcylation in the malignant
      transformation of cancer cell lines. O-GlcNAcylation level was examined in six
      cancer cell lines including breast (MCF-7 and MDA-MB-231), colorectal (SW480 and
      SW620), and liver (SK-Hep1 and HepG2). We found that the levels of O
      GlcNAcylation and O-GlcNAc transferase (OGT), an O-GlcNAc catalyzing enzyme, were
      obviously increased in all cancerous cells, except SK-Hep1, when compared to
      normal cells. Reducing O-GlcNAcylation using RNA interference against OGT showed
      a marked reduction in OGT and O-GlcNAcylation levels. Surprisingly, siOGT had no
      effect on cell growth under conventional monolayer cultures. However, it
      inhibited anchorage-independent growth in soft agar cultures of all cancer cells,
      except SK-Hep1. Under anoikis resistance conditions performed by spheroid
      cultures, siOGT treatment decreased viability only in MCF-7, SW480, and SW620
      cells. Among them, OGT knockdown in MCF-7 cells revealed a high inhibitory effect
      on colony and spheroid cultures. Using two-dimensional gel electrophoresis and
      mass spectrometric analysis, heat shock protein 27 (Hsp27) was found to be the
      highest upregulated protein upon OGT knockdown. Immunoblots revealed that the
      Hsp27 protein level was increased but its O-GlcNAc modification level was
      decreased in siOGT-treated cells. These changes were associated with the
      inhibition of MCF-7 cell transformation. Notably, double knockdown of OGT and
      Hsp27 showed a reversal in the inhibitory effect on colony and spheroid cultures.
      Collectively, these results indicate that O-GlcNAcylation is required for anoikis
      resistance and anchorage-independent growth of MCF-7 cells. Blocking this
      glycosylation by OGT knockdown may regulate both Hsp27 protein expression and its
      O-GlcNAc modification levels. This alteration may play vital roles in malignant
      transformation.

PMID- 30106437
TI  - Transcriptome-wide analysis of alternative mRNA splicing signature in the
      diagnosis and prognosis of stomach adenocarcinoma.
AB  - Alternative mRNA splicing (AS) contributes greatly to expanding the diversity and
      function of the proteome. Increasing evidence has suggested that dysregulation of
      mRNA splicing may be associated with various types of cancer. In the present
      study, RNA sequencing data were used to investigate alterations to the global
      mRNA splicing landscape of cellular genes from 452 stomach adenocarcinoma (STAD)
      tissues available in The Cancer Genome Atlas. Seven types of AS events, including
      the profiles of exon skipping events, were analyzed using SpliceSeq software. A
      total of 60,754 AS events in 10,611 genes were detected, more than half of which
      were exon skipping events. The AS events were compared between 415 STAD tissues
      and 37 normal tissues, and 3,895 differentially spliced cancer-specific events
      were identified. In addition, the association of the AS events with the overall
      survival of 373 STAD patients was analyzed. Multivariate Cox regression analysis
      revealed that prognosis prediction models based on the AS events with clinical
      parameters had an excellent performance in predicting the survival of STAD
      patients. This study provides a comprehensive portrait of global changes in mRNA
      splicing signatures that occur in gastric cancer. These results allowed the
      identification of a core set of AS in gastric cancer and indicated that AS events
      may serve as prognostic indicators.

PMID- 30106439
TI  - Zinc enhances chemosensitivity to paclitaxel in PC-3 prostate cancer cells.
AB  - Paclitaxel-based chemotherapy is a promising approach for prostate cancer
      treatment. However, single-drug chemotherapy is associated with an increased risk
      of drug resistance. Therefore, novel combination chemotherapy regimens are a
      popular topic of research. Zinc participates in the regulation of apoptosis, for
      example in the form of Zn2+ and via zinc-dependent enzymes. Zinc can either
      induce or suppress apoptosis, and its effect depends primarily on its
      concentration. Previous research has demonstrated that physiological
      concentrations of zinc can directly induce apoptosis of PC-3 prostate cancer
      cells via the mitochondrial pathway. In prostate cancer tissues, zinc
      concentrations have been demonstrated to be reduced compared with non-cancerous
      tissues. Furthermore, the concentration of zinc has been demonstrated to decrease
      further with cancer progression. In the present study, it was investigated
      whether exposure of PC-3 cells to zinc improved their sensitivity to the
      chemotherapeutic agent, paclitaxel. MTT assays, cell clone formation assays,
      Hoechst staining and flow cytometry revealed that zinc enhanced PC-3-cell
      chemosensitivity to paclitaxel. Western blotting and reverse transcription
      polymerase chain reaction were used to determine that the mitochondria-mediated
      apoptosis signaling pathway is involved with zinc/paclitaxel-induced cell death.
      The present study provides a foundation for the development of novel tumor
      combination therapy.

PMID- 30106438
TI  - Emodin induces apoptosis in human hepatocellular carcinoma HepaRG cells via the
      mitochondrial caspase-dependent pathway.
AB  - Emodin-induced hepatotoxicity in vivo and in vitro has been gaining increasing
      attention. However, the exact molecular pathways underlying these effects remain
      poorly clarified. The aim of the present study was to evaluate the cytotoxic
      effect of emodin on HepaRG cells and to define the underlying mechanism. The
      results demonstrated that emodin evidently inhibited HepaRG cell growth in a dose
      and time-dependent manner by blocking cell cycle progression in the S and G2/M
      phase and by inducing apoptosis. Emodin treatment also resulted in generation of
      reactive oxygen species (ROS), which abrogated mitochondrial membrane potential
      (MMP). The above effects were all suppressed by antioxidants, such as N
      acetylcysteine (NAC). Further studies by western blot analysis howed that emodin
      upregulated p53, p21, Bax, cyclin E, cleaved caspase-3, 8 and 9, and cleaved
      poly(ADP-ribose)polymerase (PARP). However, the protein expression of Bcl-2,
      cyclin A and CDK2 was downregulated. Taken together, our results suggest that
      emodin induces apoptosis via the mitochondrial apoptosis pathway through cell
      cycle arrest and ROS generation in HepaRG cells.

PMID- 30106440
TI  - SET7/9 promotes hepatocellular carcinoma progression through regulation of E2F1.
AB  - Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies
      worldwide. Histone-lysine N-methyltransferase SET7/9 is a protein lysine
      monomethylase that methylates histone H3K4 as well as various non-histone
      proteins. Deregulation of SET7/9 is frequently detected in human cancers.
      However, the role of SET7/9 in HCC development remains unclear. In the present
      study, upregulation of SET7/9 and E2F transcription factor 1 (E2F1) expression
      was detected in 68 samples of HCC tissues compared with these levels noted in the
      paired healthy liver samples. The expression levels of SET7/9 and E2F1 were
      significantly correlated with pathological stage and tumor size. Subcellular
      fractionation and co-immunoprecipitation analyses revealed protein-protein
      interaction between SET7/9 and E2F1 in the cytoplasm of HCC cells. Silencing of
      SET7/9, as well as treatment with 5'-deoxy-5'-methylthioadenosine (MTA), a
      protein methylation inhibitor, led to reduced E2F1 protein abundance in HCC
      cells. Using Cell Counting Kit-8 (CCK-8) assay, Transwell migration assay and
      wound healing assay, significantly decreased cell proliferation, migration and
      invasion were observed in cells exhibiting downregulation of SET7/9 and E2F1
      expression, as well as in wild-type HCC cells treated with MTA. Furthermore,
      SET7/9 downregulation and MTA treatment resulted in reduced expression of
      downstream targets of E2F1, including cyclin A2, cyclin E1 and CDK2. In
      conclusion, the present study revealed an oncogenic function of SET7/9 in HCC and
      demonstrated that SET7/9 may be responsible for alterations in the proliferative
      ability, aggressiveness and invasive/metastatic potential of HCC cells through
      post-translational regulation of E2F1.

PMID- 30106442
TI  - MicroRNA-874 is downregulated in cervical cancer and inhibits cancer progression
      by directly targeting ETS1.
AB  - An increasing number of studies have reported that microRNAs (miRNAs) are
      dysregulated in cervical cancer and serve critical roles in cervical oncogenesis
      and progression. Therefore, identifying the aberrantly expressed miRNAs
      implicated in the formation and progression of cervical cancer may provide key
      clues for the development of effective therapeutic targets in treating patients
      with this type of malignancy. In the present study, miRNA-874 (miR-874) was
      downregulated in cervical cancer tissues and cell lines, and this downregulation
      was associated with International Federation of Gynaecology and Obstetrics stage
      and lymph node metastasis. The restored expression of miR-874 prohibited the
      proliferation, migration and invasion, but promoted the apoptosis of cervical
      cancer cells. In addition, E26 transformation specific-1 (ETS1) was identified as
      the direct target of miR-874 in cervical cancer. Inhibition of ETS1 served tumour
      suppressive roles similar to miR-874 overexpression in cervical cancer cells. A
      series of rescue experiments revealed that restoring ETS1 expression abolished
      the tumour-suppressing effects of miR-874 in cervical cancer cells. Taken
      together, the results of the present study indicated that miR-874 may serve as a
      tumour suppressor in cervical cancer by directly targeting ETS1. This function
      suggested that miR-874 holds potential therapeutic applications in treating
      patients with this type of malignancy.

PMID- 30106441
TI  - Farnesoid X receptor inhibits proliferation of human colorectal cancer cells via
      the miR-135A1/CCNG2 signaling pathway.
AB  - Colorectal cancer (CRC) is among the most common malignancies of the digestive
      system. Dysregulation of miRNAs and the farnesoid X receptor (FXR) are involved
      in the progression of CRC. In the present study, the effects of FXR and miR-135A1
      in CRC were evaluated. Reverse transcription quantitative-polymerase chain
      reaction (RT-qPCR) was used to examine the expression of miR-135A1 in patient CRC
      tissues and adjacent non-tumor tissues, as well as cell lines. The association
      between miR-135A1 and clinical characteristics of patients with CRC was also
      investigated. RT-qPCR and western blotting were used to evaluate the expression
      of miR-135A1 targets. Regulation of cyclin G2 (CCNG2) by miR-135A1was confirmed
      using luciferase assays. The biological effects of miR-135A1 were assessed in
      transfected and untransfected CRC cell lines using colony formation assays, cell
      cycle analysis by flow cytometry, and CCK-8 assays. miR-135A1 was upregulated in
      CRC specimens and cell lines. miR-135A1 expression was strongly associated with
      poor cell differentiation, high expression of carbohydrate antigen (CA)125,
      CA199, carcinoembryonic antigen and survival rate of patients with CRC.
      Expression of CCNG2 was downregulated in CRC patients and cell lines, and was
      further demonstrated to be among the downstream targets of miR-135A1. The present
      study indicated that inhibition of miR-135A1 expression leads to cell cycle
      arrest and inhibition of proliferation of CRC cells via increasing CCNG2
      expression. In the present study, activation of FXR by GW4064 increased CCNG2
      expression via suppression of miR-135A1 expression, and the FXR/miR-135A1/CCNG2
      axis was demonstrated to be involved in mediating cell proliferation. In
      conclusion, activation of FXR by GW4064 suppresses cell proliferation and causes
      cell cycle arrest in CRC, and the miR-135A1/CCNG2 pathway was suggested to be
      involved in this step.

PMID- 30106443
TI  - Higenamine enhances the antitumor effects of cucurbitacin B in breast cancer by
      inhibiting the interaction of AKT and CDK2.
AB  - Cucurbitacin B (Cu B), a tetracyclic triterpenoid derived from Trichosanthes
      kirilowii Maxim, exhibits anticancer effects against various types of tumor.
      Higenamine, isolated from Radix Aconiti Lateralis Preparata, has been used as a
      dietary supplement for regulating metabolic function. The present study suggested
      that higenamine enhances Cu B-induced cytotoxicity in breast cancer cells and in
      vivo. Network pharmacology analysis was used to identify the possible mechanism
      of action. Cu B alone inhibited breast cancer cell growth, induced apoptosis, and
      arrested the cell cycle in the G2/M phase. Cu B combined with higenamine
      potentiated the cytotoxic effect of Cu B, resulting in the enhanced induction of
      apoptosis and G2/M arrest. The network pharmacology analysis also found that the
      major predicted targets of Cu B in breast cancer were AKT, endoplasmic reticulum,
      farnesyltransferase, CAAX box, alpha, platelet-derived growth factor receptor
      alpha, peroxisome proliferator-activated receptor, RET proto-oncogene, and
      vascular endothelial growth factor A. The possible targets of higenamine involved
      in the synergic action were cyclin A2, cyclin-dependent kinase 2 (CDK2),
      dihydrofolate reductase, and protein kinase CAMP-activated catalytic subunit
      alpha. The associated pathways were summarized by Kyoto Encyclopedia of Genes and
      Genomes pathway analysis, and it was hypothesized that higenamine may enhance the
      antitumor effects of Cu B in breast cancer through inhibition of the interaction
      of AKT and CDK2. The protein expression was assayed by western blot analysis. The
      combined treatment also resulted in significant inhibition of growth in vivo.

PMID- 30106444
TI  - Inhibition of YAP reverses primary resistance to EGFR inhibitors in colorectal
      cancer cells.
AB  - Mutant KRAS and BRAF are associated with primary EGFR inhibitor resistance in
      colorectal cancer (CRC). However, other biomarkers that could predict EGFR
      inhibitor resistance remain elusive. In the present study, immunoblotting and
      cell proliferation results revealed that yes-associated protein (YAP), a
      downstream effector of the Hippo pathway, was positively associated with primary
      cetuximab resistance in CRC cells. YAP knockdown enhanced the cytotoxicity of
      cetuximab in CRC cells. Simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG
      CoA) reductase inhibitor of the mevalonate pathway that inhibits YAP bioactivity
      through nuclear translocation and total YAP expression, increased the
      cytotoxicity of EGFR inhibitors (cetuximab and gefitinib) against CRC cells. The
      combination of simvastatin and EGFR inhibitors inhibited YAP and EGFR signaling
      more markedly than each agent alone. Adding back geranylgeranyl pyrophosphate
      (GGPP), a key product of the mevalonate pathway, reversed the YAP bioactivity
      inhibition induced by simvastatin and the cell proliferation inhibition induced
      by the combination of simvastatin and EGFR inhibitors. Collectively, these
      results revealed that YAP may be useful in identifying cetuximab resistance in
      CRC and indicated that targeting of both YAP and EGFR signals may present a
      promising therapeutic approach for CRC.

PMID- 30106445
TI  - miR-590-5p inhibits tumor growth in malignant melanoma by suppressing YAP1
      expression.
AB  - The microRNAs (miRNAs/miRs) involved in the carcinogenesis and progression of
      malignant melanoma (MM) remain unclear. In the present study, miR-590-5p was
      identified to be upregulated in MM cells compared with human melanocytes using a
      reverse transcription-quantitative polymerase chain reaction to screen
      established oncogenic and tumor suppressor miRNAs. miR-590-5p was demonstrated to
      inhibit the cell proliferation and tumor growth of MM cells in vitro and in vivo
      by performing Cell Counting Kit-8 and tumour xenograft assays, respectively. In
      addition, flowcytometry assays indicated that miR-590-5p induced cell apoptosis
      and cell cycle arrest at the G1 stage in MM cells. Finally, luciferase assays and
      western blot analysis results confirmed that the transcriptional regulator Yes
      associated protein 1 (YAP1) is upregulated and inversely associated with miR-590
      5p expression in MM cells, and is the direct target and functional mediator of
      miR-590-5p in MM. Altogether these results reveal the functional and mechanistic
      link between miR-590-5p and YAP1 in the progression of MM. Therefore, miR-590-5p
      is a potential therapeutic target in MM.

PMID- 30106446
TI  - Calpain 2 knockdown promotes cell apoptosis and restores gefitinib sensitivity
      through epidermal growth factor receptor/protein kinase B/survivin signaling.
AB  - Gefitinib, an epidermal growth factor receptor (EGFR)-specific drug, is effective
      for ~1 year, after which resistance is inevitable. Calpain 2 (CAPN2) is known to
      serve a role in the drug response and resistance in certain cancer therapies.
      However, the full function of CAPN2, particularly in non-small cell lung cancer,
      has not yet been elucidated. In the present study, CAPN2 expression in gefitinib
      resistant lung adenocarcinoma cells was investigated. CAPN2 function in these
      cells was further evaluated using gene knockdown both in vitro and in vivo. The
      results demonstrated that CAPN2 was strongly associated with gefitinib
      resistance, and CAPN2 mRNA and protein expression levels were significantly
      increased in gefitinib-resistant cell lines. Furthermore, CAPN2 knockdown
      inhibited gefitinib-resistant cell proliferation in vitro and in vivo. CAPN2
      conferred gefitinib-resistance by inhibiting cell apoptosis and arresting the
      cell cycle. CAPN2 knockdown also induced caspase activation and mitochondrial
      dysfunction, and its function in gefitinib resistance appeared to be largely
      mediated by EGFR/protein kinase B/survivin signaling pathway activation. These
      results suggest that CAPN2 is responsible for EGFR-tyrosine kinase inhibitor
      resistance, and CAPN2 inhibition may be used to provide therapeutic benefits in
      the treatment of gefitinib resistance.

PMID- 30106447
TI  - Long non-coding RNAs in small cell lung cancer: A potential opening to combat the
      disease (Review).
AB  - Lung cancer is the top cause of cancer-associated mortality in men and women
      worldwide. Small cell lung cancer (SCLC) is a subtype that constitutes ~15% of
      all lung cancer cases. Long non-coding RNAs (lncRNAs), possessing no or limited
      protein-coding ability, have gained extensive attention as a potentially
      promising avenue by which to investigate the biological regulation of human
      cancer. lncRNAs can modulate gene expression at the transcriptional, post
      transcriptional and epigenetic levels. The current review highlights the
      developing clinical implications and functional roles of lncRNAs in SCLC, and
      provides directions for their future utilization in the diagnosis and treatment
      of SCLC.

PMID- 30106448
TI  - MicroRNA-181a promotes cell proliferation and inhibits apoptosis in gastric
      cancer by targeting RASSF1A.
AB  - MicroRNA (miR)-181a is a member of the miR-181 family that serves a key role in
      the pathogenesis of various cancer types. The present study aimed to investigate
      the interaction between miR-181a and Ras association domain family protein1
      isoform A (RASSF1A), and their roles in gastric carcinogenesis. The interaction
      between miR-181a and RASSF1A was assessed in cell lines and cancer tissues. The
      direct binding of miR-181a and RASSF1A was identified using a luciferase
      reporting gene system. The effects of miR-181a and RASSF1A on gastric cancer cell
      growth, cell cycle and apoptosis were assessed with a Cell Counting Kit-8 assay
      and flow cytometry. The effects of miR-181a on cell division cycle 25A (CDC25A),
      cyclin A2, cyclin D1, p21, Bcl-2-associated X protein (Bax) and B-cell lymphoma-2
      (Bcl-2) protein levels were assessed in gastric cancer cell lines. miR-181a
      directly interacted with the 3'-untranslated region of RASSF1A and downregulated
      RASSF1A protein expression. In tissues from patients with gastric cancer, the miR
      181a level was significantly higher in the tumor tissues and was negatively
      correlated with the RASSF1A protein level. RASSF1A suppressed gastric cancer cell
      proliferation and G1/S transition, and promoted apoptosis; whereas miR-181a
      promoted cancer cell proliferation and G1/S transition, and suppressed apoptosis.
      RASSF1A knockdown attenuated the effects of miR-181a downregulation on cell
      proliferation and apoptosis. Furthermore, miR-181a upregulated CDC25A, cyclin A2
      and Bcl-2, and downregulated Bax protein expression in gastric cancer cell lines.
      These data indicate that miR-181a promotes gastric carcinogenesis, possibly
      through a direct interaction with RASSF1A.

PMID- 30106449
TI  - Inhibitor of apoptosis protein-like protein-2: A novel growth accelerator for
      breast cancer cells.
AB  - Although the inhibitor of apoptosis protein-like protein-2 (ILP-2) has been shown
      as a serological biomarker for breast cancer, its effect on breast cancer cell
      growth remains elusive. The present study aimed to determine the role of ILP-2 in
      breast cancer cell growth. We used immunohistochemistry to analyze ILP-2
      expression in 59 tissue paraffin-embedded blocks, which included 35 breast cancer
      tissues and 24 galactophore hyperplasia tissues. Western blot analysis was used
      to detect protein expression levels of ILP-2 in breast cancer cell lines such as
      HCC-1937, MX-1 and MCF-7 as well as breast gland cell line MCF 10A. ILP-2 was
      silenced by siRNA in HCC-1937, MX-1 and MCF-7 cell lines. MTT assays, scratch
      assays and AO-EB double staining analysis were conducted to evidence the role of
      ILP-2 on breast cancer cell growth. Results from this study showed increased ILP
      2 expression in breast cancer tissues and breast cancer cell lines such as HCC
      1937, MX-1 and MCF-7. Cell viability or rate of cell migration of HCC-1937, MX-1
      and MCF-7 cell lines was significantly inhibited when ILP-2 was knocked down by
      siRNA. The apoptosis rate of HCC-1937, MX-1 and MCF-7 cell lines was increased
      when compared with that of the control group. Thus, ILP-2 plays an active role in
      the growth of breast cancer cells.

PMID- 30106451
TI  - Association between Tim-3 and Gal-9 expression and gastric cancer prognosis.
AB  - The T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3)/galectin
      9 (Gal-9) pathway, which serves a pivotal role in immune regulation, is similar
      to the programmed death (PD)-1/PD-ligand 1 pathway. Recent evidence has suggested
      that Tim-3 is differentially regulated in a variety of tumors and is a potential
      therapeutic target. The aim of the present study was to evaluate Tim-3 and Gal-9
      expression and cluster of differentiation (CD)3+, CD8+ and forkhead box (FOX)p3+
      T cell tumor-infiltration in gastric cancer, as well as their impact on
      prognosis. Tissue samples from 587 patients with gastric cancer were used to
      create a tissue microarray (TMA). The immune markers Tim-3, Gal-9, CD3, CD8 and
      FOXp3 were immunostained in the TMA, and correlations with clinicopathological
      findings and prognosis were analyzed. Several Gene Expression Omnibus gastric
      cancer databases and the K-M plotter website were used to analyze the association
      between the expression of Tim-3, Gal-9 and CD8A RNA and patient survival. The
      results demonstrated that Tim-3 was mainly expressed in immune cells, with
      minimal expression in gastric cancer cells. Its ligand, Gal-9, was significantly
      overexpressed in tumor cells. Tim-3 and Gal-9 expression and Foxp3+ T cell
      density were negatively associated with the patient overall survival (OS) rate.
      The density of CD8+ T cells was positively associated with the patient OS rate.
      Tim-3 expression and CD8+ T cell density were revealed to be independent
      prognostic factors for patients with gastric cancer.

PMID- 30106452
TI  - Integrin beta4 reduces DNA damage-induced p53 activation in colorectal cancer.
AB  - Integrin contributes to the maintenance of cell adhesion. In turn, cell adhesion
      triggers certain integrin signaling cascades, and influences cell biological
      behavior. In the present study, we explored the role and mechanism of integrin
      beta4 in the DNA damage response in colorectal cancer (CRC) using a three
      dimensional (3D) cell culture model. Under 3D culture condition, dispersed CRC
      cells automatically formed multicellular spheroids, which consisted of layers of
      cells with cell junctions commonly distributed. The expression level of integrin
      beta4 in HCT116 3D cultures was slightly higher compared with two-dimensional
      (2D) cultures, while the expression level in LoVo 3D cultures was similar to or
      slightly lower than that in 2D cultures. Knockdown of integrin beta4 by
      lentiviral delivery of shRNA did not markedly change the architectural formation
      of 3D cultures under an inverted microscope or transmission electron microscope.
      Platinum increased p53 and p-p53 (ser15) in a time-dependent manner in 3D
      cultures. Knockdown of integrin beta4 increased sensitivity to cisplatin (CDDP)
      in 3D cultures. Under 3D culture condition, knockdown of integrin beta4 did not
      detectably change the basal p53 protein level but increased p53 and p-p53 (ser15)
      protein accumulation induced by platinum. Integrin beta4 knockdown did not
      detectably change p53 protein level in HCT116 2D cultures with or without CDDP
      treatment. Knockdown of wild-type p53 decreased sensitivity to platinum in 3D
      cultures. Since it has been proven that platinum damages DNA to kill cells and
      p53 plays a key role in the DNA damage response, our results indicated that
      integrin beta4 reduced DNA damage-induced p53 activation to decrease
      chemosensitivity in CRC. This may be due to integrin beta4 activation in 3D
      cultures.

PMID- 30106450
TI  - Downregulation of GSDMD attenuates tumor proliferation via the intrinsic
      mitochondrial apoptotic pathway and inhibition of EGFR/Akt signaling and predicts
      a good prognosis in non-small cell lung cancer.
AB  - Gasdermin D (GSDMD) is a newly discovered pyroptosis executive protein, which can
      be cleaved by inflammatory caspases and is essential for secretion of IL-1beta,
      making it a critical mediator of inflammation. However, the precise role of GSDMD
      in carcinogenesis remains nearly unknown. Considering the vital role of
      inflammation in tumorigenesis, we investigated the biological function of GSDMD
      in non-small cell lung cancer (NSCLC). Our study demonstrated that the GSDMD
      protein levels were significantly upregulated in NSCLC compared to these levels
      in matched adjacent tumor specimens. Higher GSDMD expression was associated with
      aggressive traits including larger tumor size and more advanced tumor-node
      metastasis (TNM) stages. In addition, high GSDMD expression indicated a poor
      prognosis in lung adenocarcinoma (LUAD), but not in squamous cell carcinoma
      (LUSC). Knockdown of GSDMD restricted tumor growth in vitro and in vivo. Notably,
      intrinsic and extrinsic activation of pyroptotic (NLRP3/caspase-1) signaling in
      GSDMD-deficient tumor cells induced another type of programmed cell death
      (apoptosis), instead of pyroptosis. GSDMD depletion activated the cleavage of
      caspase-3 and PARP, and promoted cancer cell death via intrinsic mitochondrial
      apoptotic pathways. In addition, co-expression analyses indicated a correlation
      between GSDMD and EGFR/Akt signaling. Collectively, our results revealed a
      crosstalk between pyroptotic signaling and apoptosis in tumor cells. Knockdown of
      GSDMD attenuated tumor proliferation by promoting apoptosis and inhibiting
      EGFR/Akt signaling in NSCLC. In conclution, GSDMD is an independent prognostic
      biomarker for LUAD.

PMID- 30106455
TI  - ?

PMID- 30106453
TI  - Conditioned medium mimicking the tumor microenvironment augments chemotherapeutic
      resistance via ataxia-telangiectasia mutated and nuclear factor-kappaB pathways
      in gastric cancer cells.
AB  - The tumor microenvironment affects the processes involved in the development of
      gastric cancer and contributes to multidrug resistance (MDR). Although the
      metabolism of gastric cancer cells is known to be associated with the development
      of the tumor microenvironment, the exact role of metabolism in microenvironment
      induced MDR formation remains unclear. In the present study, conditioned medium
      (CM) formed through the metabolism of SGC-7901 gastric carcinoma cells was used
      to mimic the tumor microenvironment. The effects of CM on drug resistance were
      evaluated in gastric carcinoma cells. The results revealed that CM was not only
      able to upregulate the expression levels of ATP-binding cassette subfamily G
      member 2 (ABCG2) and MDR-associated protein 2 (MRP2), but also upregulated the
      expression of certain anti-apoptotic proteins in SGC-7901 cells. In addition, CM
      activated the ataxia-telangiectasia mutated (ATM) and NF-kappaB pathways, while
      CM-induced ABCG2, MRP2 and anti-apoptotic protein upregulation was impaired by
      ATM and NF-kappaB inhibitors. The results of the present study indicated that CM
      augmented chemotherapeutic resistance by activating the ATM and NF-kappaB
      pathways in gastric cancer cells, and that these pathways may be potential
      therapeutic targets for cases of chemotherapeutic resistance in gastric cancer.

PMID- 30106456
TI  - [The leadless pacemaker system: present applications and future perspectives].
AB  - Cardiac devices are ever evolving, since 1958 we have come a long way from
      Senning's and Elmqvist's ingenious but crude first implantable pacemaker. The
      leadless intracardiac pacemaker (weight 2 grams) can be implanted in its entirety
      in the right ventricle through a femoral transcatheter approach. Currently, the
      leadless pacemaker system only offers VVI-mode. Studies show promising results,
      with lower complication rates than transvenous pacemaker systems. To date, there
      are no randomized controlled studies comparing leadless and transvenous
      pacemakers and no long-term follow-up. Due to this, high cost, and lack of
      experience, for now, leadless pacemakers can only be recommended for patients
      with indication for VVI pacemaker and in whom transvenous pacemaker leads are
      unfeasible. To illustrate this, we describe a case where a leadless pacemaker
      provided the solution to difficult venous access.

PMID- 30106457
TI  - ?

PMID- 30106454
TI  - Estrogen enhances tumor growth and angiogenesis indirectly via mediation of bone
      marrow-derived cells as well as directly through stimulation of tumor and
      endothelial cells.
AB  - Estradiol (E2) is a prime culprit for enhancing the progression of female hormone
      related cancers. Bone marrow-derived cells (BMDCs) have been found to play a
      pivotal role in tumor growth. Estrogen receptors (ERs) are also found on certain
      subtypes of BMDCs, in addition to endothelial cells (ECs) and certain tumor
      cells. However, the role of BMDCs in E2-induced tumor biology is still unclear.
      Thus, the effects of E2 on ER-negative 4T1 breast cancer growth, the mobilization
      and recruitment of BMDCs, and interactions among BMDCs, ECs, and 4T1 cells were
      investigated. The results showed that E2 potentiated 4T1 tumor growth and
      angiogenesis in mice subjected to sham operation, ovariectomy (OVX), or OVX and
      E2 replacement treatment. E2 supplementation in mice with OVX upregulated the
      transcription of stromal cell-derived factor-1 (SDF-1) mRNA in tumor tissues and
      enhanced the recruitment of BMDCs into tumor tissues in vivo. E2 deficiency
      significantly decreased proangiogenic CXCR4+, beta3+, Sca-1+ and CXCR4+beta3+
      BMDCs circulating in the peripheral blood. Cell-based system analyses showed that
      E2 augmented the transcription of beta3 mRNA in ECs, increased the adhesion of
      BMDCs to ECs. In addition, E2 enhanced the BMDC-induced EC proliferation and
      migration, the BMDC-induced 4T1 proliferation and the 4T1-stimulated EC
      proliferation in addition to enhancing the proliferation of tumor cells and the
      migration of ECs in vitro. Therefore, E2 enhanced the growth of breast tumors by
      stimulating tumor cells and ECs directly, as well as by increasing proangiogenic
      BMDC mobilization and recruitment leading to augmentation of the tumor and EC
      functions indirectly by cell proliferation assay. These findings reveal a
      separate mechanism via which E2 promotes the growth of female hormone-dependent
      tumors, which may be useful in explorations of new therapies for related cancers.

PMID- 30106458
TI  - ?

PMID- 30106459
TI  - Can constant light exposure affect the thyroid gland in prepubertal male albino
      rats? Histological and ultrastructural study.
AB  - BACKGROUND: Through scientific literature, there is evidence that light affects
      thyroid function in human, mice andrabbits. Constant light and sleep deprivation
      is also used as a form of human torture, as it has impact on cognitive
      performances. The present work was conducted to study the effect of constant
      light for short and long periods on the thyroid gland in the prepubertal male
      albino rats. MATERIAL AND METHODS: A total of 30 prepubertal male albino rats
      were used. The rats separated under three groups, group I (control), group II
      were those rats put under steady encompassing light (24 h/day, light intensity of
      600 lux) for four weeks. Group III were the rats maintained in constant light for
      three months. The rat thyroid gland was subjected to histological and
      ultrastructural examination. RESULTS: The rats exposed to light for long
      durations showed disturbed architecture; the follicles exhibited back to back
      arrangement (signs of hypertrophy with hyperplasia), lined by multiple layers of
      follicular cells or were lined by vacuolated cells. Few thyroid follicles were
      exhibited cystic hyperplasia. Congested blood capillaries were demonstrated
      between the follicles. CONCLUSIONS: It can be concluded that the short period of
      constant light for one month had more or less no apparent effect on thyroid gland
      tissues while longer light periods for three months brought on detrimental
      outcomes on the thyroid gland structure of male albino rats.

PMID- 30106460
TI  - Evaluation of the role of an antioxidant gene in NSC-34 motor neuron-like cells
      as a model of a motor neuron disease.
AB  - BACKGROUND: Spinal muscular atrophy is a rare genetic disease, which primarily
      affects motor neurons and predominantly occurs in children. To date, alternatives
      for the treatment of the disease have been controversial. Spinal muscular atrophy
      has a multi-factorial etiology, with mitochondrial oxidative stress considered as
      the crucial pathogenic mechanism. To determine the mechanisms underlying the loss
      of motor neurons, NSC-34 motor neuron-like cells are often used as an in vitro
      model of spinal muscular atrophy. As Plastin 3 (PLS3) has been demonstrated as a
      modifier of spinal muscular atrophy, the aim of the current study was to evaluate
      the neuroprotective effect of plastin 3 in NSC-34 cells. MATERIALS AND METHODS:
      Plastin 3 was overexpressed in human embryonic kidney 293T cells and NSC-34 cells
      via lentiviral transduction. NSC-34 cells transduced with a lentiviral vector
      carrying the gene for LacZ beta-galactosidase served as a control. Oxidative
      stress was then induced by depriving cells of serum, and the protective effect of
      plastin 3 was assessed using a cellular reactive oxygen species detection assay.
      RESULTS: While plastin 3 was successfully overexpressed in human embryonic kidney
      293T cells and NSC-34 cells, upregulation of this protein did not significantly
      decrease oxidative stress in serum-deprived NSC-34 cells relative to controls.
      CONCLUSIONS: Plastin 3 overexpression in NSC-34 cells did not elicit an
      antioxidative effect following serum deprivation.

PMID- 30106461
TI  - Inverted and horizontal impacted third molars in an Early Modern skull from
      Wroclaw, Poland: a case report.
AB  - BACKGROUND: An impacted tooth is one of the most commonly occurring dental
      anomalies, although some types of impaction (i.e. inverted angulation) may be
      considered rare finding. There are many hypotheses regarding impaction etiology.
      One of the most popular hypotheses suggested that this condition may result from
      insufficient space in retromolar space, other: improper angulation of tooth bud,
      malposition of the tooth germ or hereditary factors, insufficient interproximal
      attrition, ectopy or dysfunction of genes necessary for proper tooth eruption.
      This study aims to present the odontological and paleopathological assessment of
      the impacted molars observed within the skull excavated from an early modern
      cemetery in Wroclaw. MATERIAL AND METHODS: The skull used in the study was
      complete and in a good state of preservation. It belonged to an adult individual
      whose body was buried at the former Salvator Cemetery (currently Czysty Square).
      The individual's dentition was almost completely lost antemortem. Only second
      molars preserved within the maxillae (bilaterally) and the mandible was almost
      edentulous as well. The morphometric traits have been taken according to
      standards established by R. Martin. Macroscopic observations were supported by X
      rays and CT imaging. RESULTS: The age at death was estimated at 20-35 years.
      Comparison of the metric characteristics of skull with the reference material
      reveals, that it is much smaller than the average female skull from this series.
      Morphometric indices calculated for both splanchocranium and neurocranium allow
      defining the skull and jaw as short, which could be an important factor involved
      in the teeth impaction. CONCLUSIONS: Atypical impaction of the third molars could
      result from small size of skull and could have significantly deteriorated the
      quality of life of the individual.

PMID- 30106462
TI  - Combination of vitamin E and L-carnitine is superior in protection against
      Isoproterenol-induced cardiac affection: a histopathological evidence.
AB  - BACKGROUND: L-carnitine and Vitamin E have antioxidant properties. This study
      aimed to assess the effectiveness of L-carnitine, Vitamin E and the combination
      of them in protection against isoproterenol (ISO)-induced biochemical and
      histopathological changes in rat heart. MATERIAL AND METHODS: Fifty male Wistar
      rats assigned to 5 groups; control, ISO-treated group (100 mg/kg), ISO+vitamin E
      treated group (100 IU/kg), ISO+L-carnitine (100 mg/kg) and ISO+vitamin E+L
      carnitine treated group. At the end of the experiment, serum cardiac enzyme as
      well as the cardiac level Malondialdehyde (MDA), antioxidant enzymes and
      inflammatory cytokines IL-6, TNF-alpha were assessed. Histopathological changes
      in the left ventricle wall was assessed using the light and electron microscopy.
      RESULTS: Treating rats with vitamin E and L-carnitine could alleviate ISO-induced
      changes as it significantly reduced the serum level cardiac enzymes, MDA and IL
      6, TNF-alpha and improved the antioxidants enzymes (SOD, GSPxase and GSRase).
      Histopathological, they improved cardiac fibers atrophy, hemorrhages between
      cardiac fibers, lost striations, and disturbed sarcomere structure. The combined
      effect of vitamin E and L-carnitine was more superior compared to the other
      groups. CONCLUSION: Combined administration of vitamin E, L-carnitine ameliorated
      the biochemical and histopathological cardiac affection induced by ISO. The
      effect seemed to be mediated through the antioxidant and anti-inflammatory effect
      of vitamin E, L-carnitine. Administration of these two element is recommended for
      patient at risk for myocardial infarction.

PMID- 30106463
TI  - Renoprotective effect of red grape (Vitis vinifera L.) juice and dark raisins
      against hypercholesterolemia-induced tubular renal affection in albino rats.
AB  - BACKGROUND: Red grape juice (RGJ) and dark raisins (DR) are rich in polyphenols
      and antioxidants. This study aimed to assess the efficacy of RGJ and DR in
      protecting the renal tubules against hypercholesteremic-induced pathological
      changes. MATERIALS AND METHODS: Forty albino rats divided into 4 groups (n=10)
      were utilized in this study. They included the control, High cholesterol diet
      (HCD)-fed, HCD+RGJ)-fed, HCD+DR fed groups. Body weight gain, food and water
      intake, blood and insulin levels, lipid profile and kidney functions were
      assessed at the start of the experiment and after 12 weeks. The right kidney was
      dissected out and processed for both light and electron microscopic examination.
      Desmin and cytokeratin antibodies were utilized as histologic markers to assess
      the integrity of the proximal (PTs) and distal tubules (DTs) of the kidney.
      RESULTS: Administration of HCD resulted in hypercholesteremia in rats as evident
      by the lipid profile. The PTs of hypercholesteremic rats appeared dilated with
      hyaline casts and mitochondria in most of the tubular cells were affected.
      Immunohistochemical assessment revealed affection of both PTs and DTs. Both RGJ
      and DR, when administrated along with the HCD for 12 weeks, improved the lipid
      profile, kidney functions as well as the histologic and cellular changes-induced
      by hypercholesterolemia in the rats. The effect of raisins was superior to RGJ
      which might be due to its high contents of fibers and proteins. CONCLUSIONS: This
      study highlighted the importance of supplementation of red grape and raisins in
      protection against the harmful effects induced by deposition of fat on the renal
      tubules structure and function.

PMID- 30106464
TI  - High-Mobility Group Box 1 (HMGB1), an Endogenous Ligand of Toll-Like Receptors 2
      and 4, Induces Astroglial Inflammation via NF-?beta Pathway.
AB  - Neuroinflammation has a definitive role in neurodegenerative diseases, such as
      Parkinson's and Alzheimer's disease. In addition to its pathogenic ligands, toll
      like receptors (TLRs) can be activated by damaged endogenous molecules that
      induce inflammatory signalling pathways such as high-mobility group box 1 protein
      (HMGB1). Using an ex-vivo rat optic nerve (RON) model, we sought to determine the
      effects of lipopolysaccharides (LPS; TLR4 agonist), zymosan (TLR2 agonist) or
      HMGB1-with or without TLR2/4 antagonists, on the expression of glial fibrillary
      acidic protein (GFAP) and nuclear factor kappa B (NF-?beta) for signalling
      pathway and astrocyte reactivity, using double immunohistochemistry; as well as
      on the modulation of the neurotoxicity. HMGB1-treated RON had significant higher
      expression and co-localisation of GFAP and NF-?beta as compared to the untreated
      control, which was a similar result to those treated with LPS and zymosan.
      Moreover, the HMGB1-induced inflammation was blocked by TLR2/4 antagonists
      (P=0.05). However, the HMGB1-induced cell death was unblocked by TLR antagonists.
      Overall, HMGB1 endogenously mediates the signalling mechanisms of
      neuroinflammation through TLR2/4. Whereas, the neuronal death mechanism resulting
      from HMGB1 could be caused by a different signalling pathway. Gaining an
      understanding of these mechanisms may help researchers discover new therapeutic
      targets for neurodegenerative diseases.

PMID- 30106465
TI  - Distribution of EGFR, BMP-2, and p53 in kidney of healthy newborn, adult and old
      highland-plateau yaks.
AB  - BACKGROUND: Kidney has long been thought to be a body's largest organ of
      elimination for maintain acid-base balance. In recent years, the research on
      kidneys has mainly focused on the structural characteristics of the kidney of
      single age group animals. In this Paper we used histological and
      immunohistochemical methods to observe and compare the structure characteristics
      of yak kidney and the expression of EGFR BMP-2 and p53 in the kidney of yaks of
      three different age groups. AIMS: To investigate histological characteristics of
      age-related changes in the kidney of yak and expression and localization of
      kidney related factors. METHODS: 15 healthy males and females yaks from highland
      plateaus (three groups: newborn, adult and old yaks,n=5 per group). Histological
      methods were used to compare the relevant characteristics of the kidney of yaks.
      The immunohistochemistry method was used to observe the expression and
      localization of EGFR, BMP-2, and p53 of the kidney of different ages, and the
      optical density value was measured and analyzed by using image analysis software.
      RESULTS: Histological observations showed that yak kidneys consisted of the
      surface of the membrane and the internal substance. A substance included cortex
      and medulla, which were bounded by the arched artery. In the cortex, there were
      renal corpuscles, convoluted part of renal tubules (Proximal convoluted tubule
      and distal convoluted tubule) and collecting tubules. Medulla included straight
      part of renal tubules (Proximal straight tubule and distal straight tubule), thin
      segments and collecting tubules. It was observed that the organizational
      structure of the kidney of yaks did not change with the age, but the degree of
      development of the internal structure (glomeruli, renal tubules and collecting
      tubules) of the kidney changed with age. Immunohistochemical results demonstrated
      that EGFR, BMP-2 positive reaction in the newborn group was mainly distributed in
      the proximal tubule epithelial cells, and widely distributed in the adult and old
      groups. However, the p53 positive reaction was widely distributed from the
      newborn, adult and old groups. CONCLUSIONS: The results revealed that the kidney
      structure tended to be completed-with age, and the function of the kidney
      gradually improved. EGFR and BMP-2 had the effect of promoting kidney
      development. However, p53 had been widely distributed in the newborn kidney of
      the yaks. It is suggested that p53 had been involved in cell migration and
      metabolic differentiation and self-renewal in the new stage.

PMID- 30106466
TI  - Vitamin C attenuats the toxic effect of nutmeg on primary visual occipital cortex
      in rats.
AB  - BACKGROUND: Nutmeg is neurotoxic in rats and possibly neurotoxic also in humans.
      The aim of this study is to investigate the effect of nutmeg on the primary
      visual occipital cortex of adult male rat and to evaluate the possible protective
      role of vitamin C. MATERIALS AND METHODS: Fifty Sprague-Dawley adults male rats
      were randomly divided into three main groups; control, nutmeg-treated (500 and
      1000 mg/kg/day) and protected groups [nutmeg + vitamin C (500mg/kg/day]. All rats
      were treated orally by gavage for 5 days per week for 6 weeks. At the end of the
      experiment, primary visual occipital cerebral cortex was subjected to
      histological, immunohistochemical and genetic analyses. RESULTS: Our results
      revealed toxic effects of nutmeg on the primary visual occipital cerebral cortex
      in adult male albino rat. This was indicated by histopathological alterations,
      including pyknotic nuclei surrounded with vacuolations by light microscopic
      studies and degenerations of organelles by electron microscopic studies. In
      addition, we detected an increase in immune-reactivity for GFAP and caspase-3 by
      immunohistochemical assessments. Apoptotic bands appeared in genetic studies. Co
      administration of vitamin C ameliorated nutmeg-induced toxic alterations on the
      primary visual occipital cerebral cortex. CONCLUSIONS: Nutmeg administration
      caused histopathological and genetic changes in the primary visual occipital
      cerebral cortex in adult male albino rats. These changes were improved by co
      administration of vitamin C.

PMID- 30106467
TI  - Morphometric characteristics of the optic canal and the optic nerve.
AB  - The optic nerve (ON), a major component of the visual system, is divided into
      four segments: the intrabulbar (IB), the intraorbital (IO), the intracanalicular
      (ICn) and the intracranial (ICr). The ICr ends with the two nerves partially
      decussating in the optic chiasm (OCh). The purpose of this study is to provide a
      detailed description of the dimensions of the OC (the diameter and the surface
      area of its foramina and the central segment, as well as the length of the OC and
      the thickness of its walls) as well as the ON (the length of the ON segments, the
      diameter of the ICn segment of the ON, the angle of decussation in the OCh, as
      well as the distance between the two ON at the cranial foramen of the OC). The
      acquired data was then used to estimate the volume of the OC and the ICn segment
      of the ON. The morphometric research was performed on 25 cadavers (17 male and 8
      female) and 30 skulls. The surface area of the central segment of the OC was
      significantly smaller than the cranial foramen (p = 0.02) and the orbital foramen
      (p = 0.009). The inferior wall of the OC was significantly shorter than the other
      OC walls (p < 0.0001). The IO segment of the ON was the longest, where the
      difference to the ICn and ICr was statistically significant (p < 0.0001). The
      surface area of the ON at the cranial foramen was significantly larger than the
      surface area at the central segment of the OC (p = 0.02) and orbital foramen (p <
      0.0001). The difference between the surface areas of the ON at the orbital
      foramen and the central segment of the OC was also statistically significant (p =
      0.01).The estimated volume of the OC was calculated to be 190.72 mm3, and the
      volume of the ICn segment of the ON was estimated to be 50.25 mm3. It is
      absolutely crucial to open the central segment of the OC when decompressing the
      ON, due to the narrowing of the OC in this segment.

PMID- 30106468
TI  - Meta-analysis and Individual Participant Data Synthesis in Child Development:
      Introduction to the Special Section.
AB  - This paper serves as an Introduction by the co-editors to a Special Section of
      Child Development entitled "Meta-analysis and Individual Participant Data
      Synthesis in Child Development." First, the co-editors emphasize that the work
      contained in the Special Section was selected to highlight the value of meta
      analysis not only for synthesizing study-level published and unpublished data but
      also as regards its ability to support programmatic, replicable, and cumulative
      developmental science. Second, the co-editors identify some of the cross-cutting
      themes of the papers featured in the Special Section, including the value of meta
      analysis for summarizing and interrogating the full range of developmental
      science and in potentially transforming conventional wisdom in given domains
      along with the importance of recent innovations for improving standard meta
      analytic practice-particularly in the context of developmental questions.
      Emphasized especially are contributions to the Special Section that extend
      classic meta-analysis to individual participant data synthesis.

PMID- 30106469
TI  - Serial Stimulated Jitter Analysis In Juvenile Myasthenia Gravis.
AB  - INTRODUCTION: Clinical and electrophysiological studies to measures disease
      activity in juvenile myasthenia gravis (JMG) are limited. METHODS: Retrospective
      review of the clinical profile, Myasthenia Gravis Foundation of America (MGFA)
      scores, serial stimulated jitter analysis (Stim-JA) of the orbicularis oculi
      muscle, grip strength, and spirometry of patients with JMG who were followed in a
      multidisciplinary clinic was performed. RESULTS: Thirteen patients with JMG (9
      females) with mean age of 13.2 +/- 4.8 years and follow-up duration of 25.3 +/-
      8.3 months (range, 6-39) with >= 2 Stim-JA recordings were included. The mean
      jitter, mean percentage of apparent single-fiber action potentials (%ASFAP) with
      increased jitter, and mean %ASFAP with blocking at baseline values (77.3 +/- 54.7
      us, 64.3% +/- 35.8%, 39% +/- 38.6%, respectively) and at follow-up (53 +/- 45.4
      us, 51.2% +/- 34.5%, 17% +/- 29.4%, respectively) were abnormal; however, no
      statistically significant interval difference was noted. The electrophysiological
      data correlated significantly with Myasthenia Gravis Foundation of America (MGFA)
      class. Grip strength and spirometry did not correlate with MGFA class.
      DISCUSSION: Stimulated jitter values are sensitive biomarkers in JMG. Muscle
      Nerve 58: 729-732, 2018.

PMID- 30106470
TI  - A universal anti-cancer vaccine: Chimeric invariant chain potentiates the
      inhibition of melanoma progression and the improvement of survival.
AB  - For many years, clinicians and scientists attempt to develop methods to stimulate
      the immune system to target malignant cells. Recent data suggest that effective
      cancer vaccination requires combination immunotherapies to overcome tumor immune
      evasion. Through presentation of both MHC-I and II molecules, DCs-based vaccine
      platforms are effective in generating detectable CD4 and CD8 T cell responses
      against tumor-associated antigens. Several platforms include DC transfection with
      mRNA of the desired tumor antigen. These DCs are then delivered to the host and
      elicit an immune response against the antigen of interest. We have recently
      established an mRNA genetic platform which induced specific CD8+ cytotoxic T cell
      response by DC vaccination against melanoma. In our study, an MHC-II mRNA DCs
      vaccine platform was developed to activate CD4+ T cells and to enhance the anti
      tumor response. The invariant chain (Ii) was modified and the semi-peptide CLIP
      was replaced with an MHC-II binding peptide sequences of melanoma antigens. These
      chimeric MHC-II constructs are presented by DCs and induce proliferation of tumor
      specific CD4+ T cells. When administered in combination with the MHC-I platform
      into tumor bearing mice, these constructs were able to inhibit tumor growth, and
      improve mouse survival. Deciphering the immunological mechanism of action, we
      observed an efficient CTLs killing in addition to higher levels of Th1 and Th2
      subsets in the groups immunized with a combination of the MHC-I and MHC-II
      constructs. These universal constructs can be applied in multiple combinations
      and offer an attractive opportunity to improve cancer treatment.

PMID- 30106471
TI  - Mindfulness-based stress reduction for family carers of people with dementia.
AB  - BACKGROUND: Caring for people with dementia is highly challenging, and family
      carers are recognised as being at increased risk of physical and mental ill
      health. Most current interventions have limited success in reducing stress among
      carers of people with dementia. Mindfulness-based stress reduction (MBSR) draws
      on a range of practices and may be a promising approach to helping carers of
      people with dementia. OBJECTIVES: To assess the effectiveness of MBSR in reducing
      the stress of family carers of people with dementia. SEARCH METHODS: We searched
      ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialized
      Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (all years
      to Issue 9 of 12, 2017), MEDLINE (Ovid SP 1950 to September 2017), Embase (Ovid
      SP 1974 to Sepetmber 2017), Web of Science (ISI Web of Science 1945 to September
      2017), PsycINFO (Ovid SP 1806 to September 2017), CINAHL (all dates to September
      2017), LILACS (all dates to September 2017), World Health Organization (WHO)
      International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and
      Dissertation Abstracts International (DAI) up to 6 September 2017, with no
      language restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of
      MBSR for family carers of people with dementia. DATA COLLECTION AND ANALYSIS: Two
      review authors independently screened references for inclusion criteria,
      extracted data, assessed the risk of bias of trials with the Cochrane 'Risk of
      bias' tool, and evaluated the quality of the evidence using the GRADE instrument.
      We contacted study authors for additional information, then conducted meta
      analyses, or reported results narratively in the case of insufficient data. We
      used standard methodological procedures expected by Cochrane. MAIN RESULTS: We
      included five RCTs involving 201 carers assessing the effectiveness of MBSR.
      Controls used in included studies varied in structure and content. Mindfulness
      based stress reduction programmes were compared with either active controls
      (those matched for time and attention with MBSR, i.e. education, social support,
      or progressive muscle relaxation), or inactive controls (those not matched for
      time and attention with MBSR, i.e. self help education or respite care). One
      trial used both active and inactive comparisons with MBSR. All studies were at
      high risk of bias in terms of blinding of outcome assessment. Most studies
      provided no information about selective reporting, incomplete outcome data, or
      allocation concealment.1. Compared with active controls, MBSR may reduce
      depressive symptoms of carers at the end of the intervention (3 trials, 135
      participants; standardised mean difference (SMD) -0.63, 95% confidence interval
      (CI) -0.98 to -0.28; P<0.001; low-quality evidence). We could not be certain of
      any effect on clinically significant depressive symptoms (very low-quality
      evidence).Mindfulness-based stress reduction compared with active control may
      decrease carer anxiety at the end of the intervention (1 trial, 78 participants;
      mean difference (MD) -7.50, 95% CI -13.11 to -1.89; P<0.001; low-quality
      evidence) and may slightly increase carer burden (3 trials, 135 participants; SMD
      0.24, 95% CI -0.11 to 0.58; P=0.18; low-quality evidence), although both results
      were imprecise, and we could not exclude little or no effect. Due to the very low
      quality of the evidence, we could not be sure of any effect on carers' coping
      style, nor could we determine whether carers were more or less likely to drop out
      of treatment.2. Compared with inactive controls, MBSR showed no clear evidence of
      any effect on depressive symptoms (2 trials, 50 participants; MD -1.97, 95% CI 
      6.89 to 2.95; P=0.43; low-quality evidence). We could not be certain of any
      effect on clinically significant depressive symptoms (very low-quality
      evidence).In this comparison, MBSR may also reduce carer anxiety at the end of
      the intervention (1 trial, 33 participants; MD -7.27, 95% CI -14.92 to 0.38;
      P=0.06; low-quality evidence), although we were unable to exclude little or no
      effect. Due to the very low quality of the evidence, we could not be certain of
      any effects of MBSR on carer burden, the use of positive coping strategies, or
      dropout rates.We found no studies that looked at quality of life of carers or
      care-recipients, or institutionalisation.Only one included study reported on
      adverse events, noting a single adverse event related to yoga practices at home
      AUTHORS' CONCLUSIONS: After accounting for non-specific effects of the
      intervention (i.e. comparing it with an active control), low-quality evidence
      suggests that MBSR may reduce carers' depressive symptoms and anxiety, at least
      in the short term.There are significant limitations to the evidence base on MBSR
      in this population. Our GRADE assessment of the evidence was low to very low
      quality. We downgraded the quality of the evidence primarily because of high risk
      of detection or performance bias, and imprecision.In conclusion, MBSR has the
      potential to meet some important needs of the carer, but more high-quality
      studies in this field are needed to confirm its efficacy.

PMID- 30106473
TI  - Making the Invisible Visible: Identifying and Articulating Culture in Practice
      Based Evidence.
AB  - This study describes a conceptual tool, labeled the "culture cube," developed to
      identify and articulate the cultural underpinnings of prevention and early
      intervention projects in five priority populations (i.e., African American, Asian
      Pacific Islander, Latino, Native American, and Lesbian, Gay, Bisexual,
      Transgender, Queer, and Questioning), participating in the California Reducing
      Disparities Project Phase 2 (CRDP Phase 2). The culture cube was developed for
      evaluation of these practice-based evidence services (PBEs) for three purposes:
      (a) to focus attention on revealing and articulating more fully the operative
      worldview and culturally grounded frameworks underlying PBEs, explicitly
      identifying the links between cultural beliefs and values, community needs, and
      intervention design; (b) to guide the methods used to assess and evaluate PBEs so
      that the outcome indicators and process measures are conceptually consistent,
      community defined, and culturally centered; and (c) to invite communities to use
      their own indigenous epistemological frameworks to establish credible evidence.
      After reviewing the literature in this area and describing the theoretical
      framework for the culture cube, we describe its development, application, and the
      response to its use in the initial stages of the California Reducing Disparities
      Project-Phase 2.

PMID- 30106472
TI  - On the mechanisms of development in monocot and eudicot leaves.
AB  - Contents Summary I. Introduction II. Leaf zones in monocot and eudicot leaves
      III. Monocot and eudicot leaf initiation: differences in degree and timing, but
      not kind IV. Reticulate and parallel venation: extending the model? V. Flat
      laminar growth: patterning and coordination of adaxial-abaxial and mediolateral
      axes VI. Stipules and ligules: ontogeny of primordial elaborations VII. Leaf
      architecture VIII. Stomatal development: shared and diverged mechanisms for
      making epidermal pores IX. Conclusion Acknowledgements References SUMMARY:
      Comparisons of concepts in monocot and eudicot leaf development are presented,
      with attention to the morphologies and mechanisms separating these angiosperm
      lineages. Monocot and eudicot leaves are distinguished by the differential
      elaborations of upper and lower leaf zones, the formation of
      sheathing/nonsheathing leaf bases and vasculature patterning. We propose that
      monocot and eudicot leaves undergo expansion of mediolateral domains at different
      times in ontogeny, directly impacting features such as venation and leaf bases.
      Furthermore, lineage-specific mechanisms in compound leaf development are
      discussed. Although models for the homologies of enigmatic tissues, such as
      ligules and stipules, are proposed, tests of these hypotheses are rare. Likewise,
      comparisons of stomatal development are limited to Arabidopsis and a few grasses.
      Future studies may investigate correlations in the ontogenies of parallel
      venation and linear stomatal files in monocots, and the reticulate patterning of
      veins and dispersed stoma in eudicots. Although many fundamental mechanisms of
      leaf development are shared in eudicots and monocots, variations in the timing,
      degree and duration of these ontogenetic events may contribute to key differences
      in morphology. We anticipate that the incorporation of an ever-expanding number
      of sequenced genomes will enrich our understanding of the developmental
      mechanisms generating eudicot and monocot leaves.

PMID- 30106474
TI  - Subjective Well-Being Decreasing With Age: New Research on Children Over 8.
AB  - An increasing number of scientific publications have provided data from different
      countries suggesting subjective well-being (SWB) continuously decreases during
      adolescence. A review of these publications reveals authors have used dissimilar
      scales in diverse countries. Using data from the international Children's Worlds
      project (N = 48,040), involving 15 countries, a comparative analysis was
      performed to determine how mean scores evolve with different SWB scales from the
      age of 8 onwards. The results support the hypothesis that the tendency of SWB to
      decrease with age starts at around 10 years of age in most countries, while also
      confirming that different psychometric scales display different levels of
      sensitivity to diverse sociocultural contexts and more than one should be used in
      any research on children and adolescents' SWB.

PMID- 30106475
TI  - B cells in the pathophysiology of myasthenia gravis: Is there a role for
      cladribine?
AB  - No abstract is available for this article. This article is protected by
      copyright. All rights reserved.

PMID- 30106476
TI  - Physicochemical, Microstructural, and Microbiological Properties of Skipjack Tuna
      (Katsuwonus pelamis) After High-Pressure Processing.
AB  - : Properties of skipjack tuna loins subjected to high-pressure processing (HPP)
      at 150 to 600 MPa for 1 to 5 min were compared with those of loin that underwent
      steam cooking for 10 min. Protein denaturation in HPP-treated loins increased
      with increasing pressure level, but these loins retained between 1.1% and 2.4%
      more water than steam-cooked loin. Water holding capacity decreased from 57% to
      44% when the loins were treated at 600 MPa. DeltaE value of HPP loins was between
      5.8 and 26.3 when treated at 150 to 600 MPa, whereas it was 34.1 for steam-cooked
      sample. Hardness of HPP loins increased from 648 to 1,019, 1,918, 5,249, and
      4,092 g and springiness changed from 85.2% to 79.7%, 78.2%, 91.7%, and 90.7%,
      respectively, when treated at 150, 300, 450, and 600 MPa. Protein fibers of HPP
      loins had a more irregular shape than those of steam-treated loin. Histamine
      levels of HPP-treated loins were in the range of 3.08 to 3.35 MUg/g, identical to
      that of steam-treated loin. Thiobarbituric acid assay demonstrated that the level
      of lipid oxidation increment in HPP-treated loins was twice as high as that in
      steam-cooked one. Undesirable volatile compound contents in tuna loins decreased
      with increasing degree of protein denaturation. Steam cooking and HPP at 150,
      300, 450, and 600 MPa decreased the total aerobic counts by 4.75, 0.12, 1.20,
      4.69, and 6.08 log CFU/g, respectively. These results suggest that HPP at 450 MPa
      and above has the potential to be used as an alternative to the tuna precooking
      process. PRACTICAL APPLICATION: Information presented here can serve as a
      guideline for the selection of appropriate conditions for HPP of tuna loins. Our
      results show that HPP has a potential to replace the highly energy-intensive
      steam precooking step, which is traditionally required in a canned tuna
      production process.

PMID- 30106477
TI  - Coordination between leaf, stem, and root hydraulics and gas exchange in three
      arid-zone angiosperms during severe drought and recovery.
AB  - The ability to resist hydraulic dysfunction in leaves, stems, and roots strongly
      influences whether plants survive and recover from drought. However, the
      coordination of hydraulic function among different organs within species and
      their links to gas exchange during drought and recovery remains understudied.
      Here, we examine the interaction between gas exchange and hydraulic function in
      the leaves, stems, and roots of three semiarid evergreen species exposed to a
      cycle of severe water stress (associated with substantial cavitation) and
      recovery. In all species, stomatal closure occurred at water potentials well
      before 50% loss of stem hydraulic conductance, while in two species, leaves
      and/or roots were more vulnerable than stems. Following soil rewetting, leaf
      level photosynthesis (Anet ) returned to prestress levels within 2-4 weeks,
      whereas stomatal conductance and canopy transpiration were slower to recover. The
      recovery of Anet was decoupled from the recovery of leaf, stem, and root
      hydraulics, which remained impaired throughout the recovery period. Our results
      suggest that in addition to high embolism resistance, early stomatal closure and
      hydraulic vulnerability segmentation confers drought tolerance in these arid zone
      species. The lack of substantial embolism refilling within all major organs
      suggests that vulnerability of the vascular system to drought-induced dysfunction
      is a defining trait for predicting postdrought recovery.

PMID- 30106478
TI  - On the double: Early immunotherapy speeds recovery of ocular myasthenic weakness.

PMID- 30106479
TI  - A mother's gift: consequences of unhealthy diet for offspring metabolism.

PMID- 30106480
TI  - Replisome-Cohesin Interfacing: A Molecular Perspective.
AB  - Cohesion is established in S-phase through the action of key replisome factors as
      replication forks engage cohesin molecules. By holding sister chromatids
      together, cohesion critically assists both an equal segregation of the duplicated
      genetic material and an efficient repair of DNA breaks. Nonetheless, the
      molecular events leading the entrapment of nascent chromatids by cohesin during
      replication are only beginning to be understood. The authors describe here the
      essential structural features of the cohesin complex in connection to its ability
      to associate DNA molecules and review the current knowledge on the architectural
      functional organization of the eukaryotic replisome, significantly advanced by
      recent biochemical and structural studies. In light of this novel insight, the
      authors discuss the mechanisms proposed to assist interfacing of replisomes with
      chromatin-bound cohesin complexes and elaborate on models for nascent chromatids
      entrapment by cohesin in the environment of the replication fork.

PMID- 30106481
TI  - Does anxiety trigger fasciculations?

PMID- 30106482
TI  - Cough peak flow decline rate predicts survival in patients with amyotrophic
      lateral sclerosis.
AB  - INTRODUCTION: In this study we investigated the prognostic significance of cough
      peak flow (CPF) decline rate in patients with amyotrophic lateral sclerosis
      (ALS). METHODS: Thirty-four patients with ALS participated in our investigation.
      We examined CPF, forced vital capacity (FVC), body mass index, and the revised
      ALS Functional Rating Scale (ALSFRS-R), and followed patients to death,
      tracheostomy, or non-invasive ventilator dependency. We analyzed the relationship
      between the rate of decline of each parameter and survival prognosis. RESULTS:
      The CPF decline rate significantly correlated with the decline rates of the
      ALSFRS-R bulbar score (P < 0.0001) and FVC (P < 0.0001). Patients with a CPF
      decline rate >=25% had shorter overall survival (P < 0.0001). Cox model
      multivariate analyses showed that the CPF decline rate was an independent
      prognostic factor for survival (P = 0.021). DISCUSSION: The CPF decline rate
      reflects the progression of bulbar and respiratory dysfunction and predicts
      survival. Muscle Nerve, 2018.

PMID- 30106483
TI  - Keto diets: good, bad or ugly?

PMID- 30106484
TI  - Phantastic phagocytes.

PMID- 30106485
TI  - Rapid growth of scalp melanoma in a pediatric patient.

PMID- 30106486
TI  - Navigating Complex Implementation Contexts: Overcoming Barriers and Achieving
      Outcomes in a National Initiative to Scale Out Housing First in Canada.
AB  - The scaling out of Housing First (HF) programs was examined in six Canadian
      communities, in which a multi-component HF training and technical assistance
      (TTA) was provided. Three research questions were addressed: (a) What were the
      outcomes of the TTA in terms of the development of new, sustained, or enhanced
      programs, and fidelity to the HF model? (b) How did the TTA contribute to
      implementation and fidelity? and (c) What contextual factors facilitated or
      challenged implementation and fidelity? A total of 14 new HF programs were
      created, and nine HF programs were sustained or enhanced. Fidelity assessments
      for 10 HF programs revealed an average score of 3.3/4, which compares favorably
      with other HF programs during early implementation. The TTA influenced fidelity
      by addressing misconceptions about the model, encouraging team-based practice,
      and facilitating case-based dialogue on site specific implementation challenges.
      The findings were discussed in terms of the importance of TTA for enhancing the
      capacities of the HF service delivery system-practitioners, teams, and
      communities-while respecting complex community contexts, including differences in
      policy climate across sites. Policy climate surrounding accessibility of housing
      subsidies, and use of Assertive Community Treatment teams (vs. Intensive Case
      Management) were two key implementation issues.

PMID- 30106487
TI  - Architectural Designs and Synthetic Strategies of Advanced Nanocatalysts.
AB  - Advanced nanocatalysts with high compositional and structural tailorability have
      emerged as a new class of heterogeneous catalysts exhibiting many new technical
      merits over their conventional counterparts. Generally, preparation of such
      catalysts involves the integration of catalyst components with compositional,
      size, and shape controls into a larger material system in order to bring along
      collective and synergetic effects of individual components. Herein, a brief
      review of architectural designs and synthetic strategies for making these
      nanocatalysts is presented. Due to length constraints, only four major types of
      them are highlighted together with some general rules of design and synthesis.
      Finally, a critical outline of future perspective in this field is proposed.

PMID- 30106488
TI  - Observation of Circularly Polarized Luminescence of the Excimer from Two Perylene
      Cores in the Form of [4]Rotaxane.
AB  - A perylene-based [4]rotaxane was synthesized by the Sonogashira coupling of the
      2:2 inclusion complex consisting of two alkynylperylenes and two gamma
      cyclodextrins with terphenyl-type stopper molecules. The [4]rotaxane showed
      orange emission attributable to the spatially restricted alkynylperylene excimer
      with a high fluorescence quantum yield of Phif =0.15. The excimer emission was
      circularly polarized as a result of the asymmetrically twisted perylene pair
      under the influence of chirality of gamma-cyclodextrin. The glum value of the
      excimer emission was determined to be -2.1*10-2 at 573 nm, as large as those of
      the corresponding known pyrene-based series. This is the first example, in which
      circularly polarized luminescence was clearly observed from the excimer of a pair
      of perylene cores.

PMID- 30106489
TI  - Adherence to extended release naltrexone: Patient and treatment characteristics.
AB  - BACKGROUND AND OBJECTIVES: Despite the promise of extended release naltrexone in
      the treatment of the opioid and alcohol use disorders, challenges with initiation
      and subsequent adherence have limited its potential. The purpose of this study is
      to identify the patient and treatment characteristics associated with adherence
      to extended release naltrexone. METHODS: Retrospective cohort study of 155
      veterans who initiated the medication in FY 2014 and FY2015. Medical records were
      abstracted for patient and treatment data including preferred drug and
      utilization of substance use treatment in the year before and after medication
      initiation. RESULTS: Sample characteristics include 94% male, 70% domiciled, 60%
      without current legal problems, 30% employed, and preferred drug being opioids
      for 55% and alcohol for 45%. The mean of five extended release naltrexone
      injections did not differ by preferred drug. Treatment variables associated with
      medication adherence included concurrent substance use residential, individual,
      group, and psychiatric therapies (all p < .05) with inpatient detoxification
      admissions halved afterward (p < .0001) . DISCUSSION AND CONCLUSIONS: Whereas
      most studies of extended release naltrexone have focused on patients with either
      alcohol or opioid use disorders for 6 months, this study allowed for a direct
      comparison of adherence in both groups over a year. The average treatment
      persistence in this veteran sample is greater than described in other public
      sector studies and may illustrate the importance of concurrent psychosocial
      therapies. SCIENTIFIC SIGNIFICANCE: Results extend the findings of other studies
      and add to an emerging appreciation of the factors associated with treatment
      retention for extended release naltrexone. (Am J Addict 2018;27:524-530).

PMID- 30106490
TI  - Allergic asthma: RIPK2 takes the lead.

PMID- 30106491
TI  - Synthesis of Aliphatic Carboxamides Mediated by Nickel NN2 -Pincer Complexes and
      Adaptation to Carbon-Isotope Labeling.
AB  - The development of a nickel-mediated aminocarbonylation utilizing NN2 -pincer Ni
      complexes, alkylzinc reagents, stoichiometric carbon monoxide and amines is
      described for the first time, which can be adapted to late-stage carbon-isotope
      labeling. This work expands the scope of the highly established palladium
      promoted version of the reaction, by allowing carbon-sp3 fragments to take part
      in the three-component reaction. Finally, the results obtained show a remarkable
      effect of the pincer ligand for the reductive elimination step with the amine,
      which is followed by 13 C NMR spectroscopy studies.

PMID- 30106493
TI  - Epigenetic Aging in Osteoporosis.

PMID- 30106492
TI  - Reply to: Association Between Alendronate and All-Cause Mortality and
      Cardiovascular Mortality Among Hip Fracture: An Alternative Explanation.

PMID- 30106494
TI  - Gender differences in demographic and clinical characteristics of patients with
      opioid use disorder entering a comparative effectiveness medication trial.
AB  - BACKGROUND & OBJECTIVES: We investigated gender differences in individuals with
      opioid use disorder (OUD) receiving inpatient services and entering a randomized
      controlled trial comparing extended-release naltrexone to buprenorphine. METHODS:
      Participants (N = 570) provided demographic, substance use, and psychiatric
      information. RESULTS: Women were significantly younger, more likely to identify
      as bisexual, live with a sexual partner, be financially dependent, and less
      likely employed. Women reported significantly greater psychiatric comorbidity and
      risk behaviors, shorter duration but similar age of onset of opioid use.
      DISCUSSION/CONCLUSIONS: Findings underscore economic, psychiatric, and infection
      vulnerability among women with OUD. SCIENTIFIC SIGNIFICANCE: Interventions
      targeting these disparities should be explored, as women may face complicated
      treatment initiation, retention, and recovery. (Am J Addict 2018;27:465-470).

PMID- 30106496
TI  - Association Between Alendronate and All-Cause Mortality and Cardiovascular
      Mortality Among Hip Fracture: An Alternative Explanation.

PMID- 30106495
TI  - Effective Differentiation of Induced Pluripotent Stem Cells Into Dental Cells.
AB  - BACKGROUND: A biotooth is defined as a complete living tooth, made in laboratory
      cultures from a spontaneous interplay between epithelial and mesenchymal cell
      based frontal systems. A good solution to these problems is to use induced
      pluripotent stem cells (iPSCs). However, no one has yet formulated culture
      conditions that effectively differentiate iPSCs into dental epithelial and dental
      mesenchymal cells phenotypes analogous to those present in tooth development.
      RESULTS: Here, we tried to induce differentiation methods for dental epithelial
      cells (DEC) and dental mesenchymal cells from iPSCs. For the DEC differentiation,
      the conditional media of SF2 DEC was adjusted to embryoid body. Moreover, we now
      report on a new cultivation protocol, supported by transwell membrane cell
      culture that make it possible to differentiate iPSCs into dental epithelial and
      mesenchymal cells with abilities to initiate the first stages in de novo tooth
      formation. CONCLUSIONS: Implementation of technical modifications to the protocol
      that maximize the number and rate of iPSC differentiation, into mesenchymal and
      epithelial cell layers, will be the next step toward growing an anatomically
      accurate biomimetic tooth organ.

PMID- 30106497
TI  - Spatially Separating the Conformers of a Dipeptide.
AB  - Atomic-resolution-imaging approaches for single molecules, such as coherent X-ray
      diffraction at free-electron lasers, require the delivery of high-density beams
      of identical molecules. However, even very cold beams of biomolecules typically
      have multiple conformational states populated. We demonstrate the production of
      very cold (Trot ~2.3 K) molecular beams of intact dipeptide molecules, which were
      then spatially separated into the individual populated conformational states.
      This is achieved using the combination of supersonic expansion laser-desorption
      vaporization with electrostatic deflection in strong inhomogeneous fields. This
      represents the first demonstration of a conformer-separated and rotationally cold
      molecular beam of a peptide, which enables the investigation of conformer
      specific chemistry using inherently non-conformer-specific techniques. It
      furthermore represents a milestone toward the direct structural imaging of
      individual biological molecules with atomic resolution by ultrafast diffractive
      imaging methods.

PMID- 30106499
TI  - Perspectives of Microwaves-Enhanced Heterogeneous Catalytic Gas-Phase Processes
      in Flow Systems.
AB  - The paper discusses the currents status and future perspectives of the
      utilization of microwaves, as a selective and locally controlled heating method,
      in heterogeneous catalytic flow reactors. Various factors related to the
      microwave-catalyst interaction and the design of microwave-assisted catalytic
      reactor systems are analyzed. The analysis clearly shows the superiority of the
      traveling-wave systems over the mono-mode and multi-mode cavity-based systems
      when it comes to the design and application of microwave flow reactors at
      relevant production scales.

PMID- 30106498
TI  - FLP-Catalyzed Transfer Hydrogenation of Silyl Enol Ethers.
AB  - Herein we report the first catalytic transfer hydrogenation of silyl enol ethers.
      This metal free approach employs tris(pentafluorophenyl)borane and 2,2,6,6
      tetramethylpiperidine (TMP) as a commercially available FLP catalyst system and
      naturally occurring gamma-terpinene as a dihydrogen surrogate. A variety of silyl
      enol ethers undergo efficient hydrogenation, with the reduced products isolated
      in excellent yields (29 examples, 82 % average yield).

PMID- 30106500
TI  - JAGN1 is required for fungal killing in neutrophil extracellular traps:
      Implications for severe congenital neutropenia.
AB  - Mutations in the gene JAGN1 were recently discovered in patients with severe
      congenital neutropenia (SCN). Neutrophils release neutrophil extracellular traps
      (NETs) consisting of decondensed chromatin decorated with various granular
      proteins such as neutrophil elastase and myeloperoxidase (MPO) to combat
      microbial infections. However, whether JAGN1 is required for the formation or
      function of NETs is not known. Here, we analyzed primary neutrophils from a
      patient with homozygous JAGN1 mutations with respect to phorbol myristate acetate
      (PMA)-induced NET formation. NET release was observed, but there appeared to be a
      reduced level of expression of MPO in the NETs. To study this further, we
      differentiated HL-60 cells into neutrophil-like cells and silenced JAGN1
      expression by transfection with siRNA. These cells remained capable of producing
      NETs, but MPO expression was severely affected, and NETs released by JAGN1
      silenced cells were ineffective in killing Candida albicans. The candidacidal
      function was restored upon treatment with GM-CSF or addition of MPO. GM-CSF also
      up-regulated the expression of calprotectin in NETs. Notably, JAGN1 did not
      impact on N-glycosylation of MPO in neutrophil-like HL-60 cells. These studies
      shed light on the susceptibility of SCN patients to fungal infections and the
      role of JAGN1 for the antimicrobial function of neutrophils exerted by NETs.

PMID- 30106501
TI  - c-MPL Is a Candidate Surface Marker and Confers Self-Renewal, Quiescence,
      Chemotherapy Resistance, and Leukemia Initiation Potential in Leukemia Stem
      Cells.
AB  - Acute myeloid leukemia (AML) is initiated and maintained by a unique, small
      subset of leukemia cells known as leukemia stem cells (LSCs). Self-renewal,
      quiescence, and chemotherapy resistance are key stemness properties of LSCs that
      are essential for poor clinical responses to conventional therapies. Identifying
      LSC surface markers and targeting LSCs are important for the development of
      potential therapies. In this study, application of chemotherapy treatment in AML
      ETO9a (AE9a) leukemia mice led to the enrichment of a chemotherapy-resistant cell
      population identified as Lin- c-Kit+ c-MPL+ . In addition, this c-MPL-positive
      cell population within Lin- c-Kit+ leukemia cells included a high percentage of
      cells in a quiescent state, enhanced colony formation ability, and increased
      homing efficiency. Serial transplantation demonstrated that Lin- c-Kit+ c-MPL+
      cells displayed a significantly high potential for leukemia initiation.
      Furthermore, it was demonstrated that in AML patients, c-MPL was expressed on the
      majority of CD34+ leukemia cells and that the proportion of c-MPL+ cells in CD34+
      leukemia cells is associated with poor prognosis. Finally, AMM2, an inhibitor of
      c-MPL, was shown to significantly enhance the survival of AE9a leukemia mice when
      combined with chemotherapeutic agent. These results indicate that c-MPL is a
      candidate LSC surface marker that may serve as a therapeutic target for the
      elimination of LSCs. Stem Cells 2018;36:1685-1696.

PMID- 30106502
TI  - Survey of aged psychiatry services' support of older Australians with very
      severe, persistent behavioural symptoms of dementia.
AB  - OBJECTIVE: To map the provision of community, acute, non-acute and residential
      care-based state-funded mental health services to older people with severe,
      persistent behavioural symptoms of dementia. METHODS: An electronic survey was
      completed in 2015 by senior representatives of aged persons' mental health
      services across Australia's six states. RESULTS: Jurisdictions varied widely in
      the number, geographic spread and make-up of aged persons' mental health
      community teams when adjusted for aged population; their number of acute and non
      acute beds, and especially in the provision of specialist residential beds or
      partnerships with non-government providers. CONCLUSION: There is no nationally
      accepted pathway of care for this vulnerable group or understanding of what
      constitutes an adequate statewide mental health service.

PMID- 30106503
TI  - The Conformational Ensemble of Polyglutamine-14 Chains: Specific Influences of
      Solubility Tail and Chromophores.
AB  - We address polyglutamine-14 in aqueous solution with specific chromophores and a
      solubility chain by means of a multiscale simulation approach, combining
      atomistic molecular dynamics simulations and coarse-grained Monte-Carlo
      conformational sampling. Despite the intrinsically disordered nature of the
      amyloidogenic polyglutamine, we observe transient characteristic structural
      motifs which exhibit a specific hydrogen bonding pattern. We illustrate the
      relationship between structure pattern and the distance distribution of a pair of
      chromophores attached to the peptide termini, in light of specific influence of a
      short solubility tail and the chromophores themselves on the conformational
      ensemble.

PMID- 30106504
TI  - Light-Driven Enzymatic Decarboxylation of Fatty Acids.
AB  - The photoenzymatic decarboxylation of fatty acids to alkanes is proposed as an
      alternative approach for the synthesis of biodiesel. By using a recently
      discovered photodecarboxylase from Chlorella variabilis NC64A (CvFAP) we
      demonstrate the irreversible preparation of alkanes from fatty acids and
      triglycerides. Several fatty acids and their triglycerides are converted by CvFAP
      in near-quantitative yield and exclusive selectivity upon illumination with blue
      light. Very promising turnover numbers of up to 8000 were achieved in this proof
      of-concept study.

PMID- 30106505
TI  - Organic Solar Cell Materials toward Commercialization.
AB  - Bulk-heterojunction organic solar cells (OSCs) have received considerable
      attention with significant progress recently and offer a promising outlook for
      portable energy resources and building-integrated photovoltaics in the future.
      Now, it is urgent to promote the research of OSCs toward their commercialization.
      For the commercial application of OSCs, it is of great importance to develop high
      performance, high stability, and low cost photovoltaic materials. In this review,
      a comprehensive overview of the fundamental requirements of photoactive layer
      materials and interface layer materials toward commercialization is provided,
      mainly focusing on high performance, green manufacturing, simplifying device
      fabrication processes, stability, and cost issues. Furthermore, the perspectives
      and opportunities for this emerging field of materials science and engineering
      are also discussed.

PMID- 30106506
TI  - Toward Tailorable Zn-Ion Textile Batteries with High Energy Density and Ultrafast
      Capability: Building High-Performance Textile Electrode in 3D Hierarchical
      Branched Design.
AB  - Rechargeable Zn-ion batteries are promising candidates for wearable energy
      storage devices. However, their performance is severely restricted by the low
      conductivity and inferior mass loading. Herein, a new type of the textile based
      electrodes with 3D hierarchical branched design is reported. Both Ni
      nanoparticles and carbon nanotubes are used to build conductive coatings on the
      textiles. The 3D hierarchical nanostructures, consisting of the vertical-aligned
      nanosheets and the fluffy-like small flakes, grow on the conductive textiles to
      form the self-supported electrodes. It ensures fast electron/ion transport and
      high mass loading, and maintains the structure stability during cycling. Two
      textile electrodes with the NiCo hydroxide and MnO2 self-branched nanostructures
      are constructed. Their faster kinetics, higher capacity and better rate
      capability than the solitary nanosheets based counterpart demonstrate the
      superiority of the hierarchical architecture. Moreover, the solid-state Zn-MnO2
      and Zn-NiCo batteries are fabricated based on the textile electrodes and the
      polymer electrolytes. The high energy density, superior power density and good
      long-term cycling stability confirm their excellent energy storage ability and
      fast charge/discharge capability. Particularly, the high safety under various
      conditions enable them promising candidates for wearable electronics.

PMID- 30106507
TI  - From Exceptional Properties to Stability Challenges of Perovskite Solar Cells.
AB  - The discovery and development of organic-inorganic halide perovskites with
      exceptional properties has become an active research area in the field of
      photovoltaics. Perovskite solar cells (PSCs) have attracted much attention in
      recent years due to various attractive advantages, such as simple solution
      processing, low manufacturing cost, and high performances with power conversion
      efficiencies now reaching certified values close to 23% within a very short time
      frame of five years. Despite this rapid progress, the inferior device stability
      remains a great challenge. This review focuses on the factors limiting the
      stability of PSCs, such as humidity, heat, and irradiation, summarizing recent
      strategies to overcome stability and fabrication obstacles in order to open new
      perspectives to achieve highly durable perovskite devices toward future
      industrialization.

PMID- 30106508
TI  - Perfluorinated Covalent Triazine Framework Derived Hybrids for the Highly
      Selective Electroconversion of Carbon Dioxide into Methane.
AB  - Developing cost-effective electrocatalysts for high-selectivity CO2
      electroreduction remains challenging. We herein report a perfluorinated covalent
      triazine framework (CTF) electrocatalyst that displays very high selectivity in
      the electroreduction of CO2 to CH4 with a faradaic efficiency of 99.3 % in
      aqueous electrolyte. Systematic characterization and electrochemical studies, in
      combination with density functional theory calculations, demonstrate that the
      presence of both nitrogen and fluorine in the CTF provides a unique pathway that
      is inaccessible with the individual components for CO2 electroreduction.

PMID- 30106509
TI  - Low-Temperature Continuous-Flow Dehydration of Xylose Over Water-Tolerant Niobia
      Titania Heterogeneous Catalysts.
AB  - The sustainable conversion of vegetable biomass-derived feeds to useful chemicals
      requires innovative routes meeting environmental and economical criteria. The
      approach herein pursued is the synthesis of water-tolerant, unconventional solid
      acid monolithic catalysts based on a mixed niobia-titania skeleton building up a
      hierarchical open-cell network of meso- and macropores, and tailored for use
      under continuous-flow conditions. The materials were characterized by
      spectroscopic, microscopy, and diffraction techniques, showing a reproducible
      isotropic structure and an increasing Lewis/Bronsted acid sites ratio with
      increasing Nb content. The catalytic dehydration reaction of xylose to furfural
      was investigated as a representative application. The efficiency of the catalyst
      was found to be dramatically affected by the niobia content in the titania
      lattice. The presence of as low as 2 wt % niobium resulted in the highest
      furfural yield at 140  degrees C under continuous-flow conditions, by using H2
      O/gamma-valerolactone as a safe monophasic solvent system. The interception of a
      transient 2,5-anhydroxylose species suggested the dehydration process occurs via
      a cyclic intermediates mechanism. The catalytic activity and the formation of the
      anhydro intermediate were related to the Lewis acid sites (LAS)/Bronsted acid
      sites (BAS) ratio and indicated a significant contribution of xylose-xylulose
      isomerization. No significant catalyst deactivation was observed over 4 days
      usage.

PMID- 30106510
TI  - Does autonomic re-innervation cause Takotsubo syndrome in a transplanted heart?
      Comment on: "Takotsubo cardiomyopathy in a young adult with transplanted heart:
      what happened to denervation?" by Chinali et al.

PMID- 30106511
TI  - Computational Prediction of Carbohydrate-Binding Proteins and Binding Sites.
AB  - Protein-carbohydrate interaction is essential for biological systems, and
      carbohydrate-binding proteins (CBPs) are important targets when designing
      antiviral and anticancer drugs. Due to the high cost and difficulty associated
      with experimental approaches, many computational methods have been developed as
      complementary approaches to predict CBPs or carbohydrate-binding sites. However,
      most of these computational methods are not publicly available. Here, we provide
      a comprehensive review of related studies and demonstrate our two recently
      developed bioinformatics methods. The method SPOT-CBP is a template-based method
      for detecting CBPs based on structure through structural homology search combined
      with a knowledge-based scoring function. This method can yield model complex
      structure in addition to accurate prediction of CBPs. Furthermore, it has been
      observed that similarly accurate predictions can be made using structures from
      homology modeling, which has significantly expanded its applicability. The other
      method, SPRINT-CBH, is a de novo approach that predicts binding residues directly
      from protein sequences by using sequence information and predicted structural
      properties. This approach does not need structurally similar templates and thus
      is not limited by the current database of known protein-carbohydrate complex
      structures. These two complementary methods are available at https://sparks
      lab.org. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30106512
TI  - Three-Dimensional Printing of Archived Human Fetal Material for Teaching
      Purposes.
AB  - The practical aspect of human developmental biology education is often limited to
      the observation and use of animal models to illustrate developmental anatomy.
      This is due in part to the difficulty of accessing human embryonic and fetal
      specimens, and the sensitivity inherent to presenting these specimens as teaching
      materials. This report presents a new approach using three-dimensional (3D)
      printed replicas of actual human materials in practical classes, thus allowing
      for the inclusion of accurate examples of human developmental anatomy in the
      educational context. A series of 3D prints have been produced from digital data
      collected by computed tomography (CT) imaging of an archived series of preserved
      human embryonic and fetal specimens. The final versions of 3D prints have been
      generated in a range of single or multiple materials to illustrate the
      progression of human development, including the development of internal anatomy.
      Furthermore, multiple copies of each replica have been printed for large group
      teaching. In addition to the educational benefit of examining accurate 3D
      replicas, this approach lessens the potential for adverse student reaction (due
      to cultural background or personal experience) to observing actual human
      embryonic/fetal anatomical specimens, and reduces the potential of damage or loss
      of original specimens. This approach, in combination with ongoing improvements in
      the management and analysis of digital data and advances in scanning technology,
      has enormous potential to allow embryology students access to both local and
      international collections of human gestational material. Anat Sci Educ 00: 000
      000. (c) 2018 American Association of Anatomists.

PMID- 30106513
TI  - Unveiling the Mechanism of Surface Hydrophilicity-Modulated Macrophage
      Polarization.
AB  - With inflammation increasingly recognized as a key factor that influences
      fracture healing, the immunologic response is considered to play a pivotal role
      in determining implant-mediated osteogenesis. Herein, this paper demonstrates
      that modification of the surface hydrophilicity of Ti surface oxides can be
      utilized to control immune response by steering the macrophage polarization
      toward pro- or anti-inflammation phenotype. Enhanced anti-inflammatory and
      prohealing performance of macrophages is observed on hydrophilic surfaces
      compared to hydrophobic ones. Further study on the detailed mechanism
      demonstrates that the surface hydrophilicity controls specific proteins
      (fibronectin and fibrinogen) adsorption and conformation, which activate
      different signaling pathways (PI3K and NF-kappaB) through selective expression of
      integrin beta1 or beta2 to influence the behaviors of macrophages. Thus, this
      study presents a mechanism of macrophage polarization modulated by surface
      hydrophilicity for the surface design of advanced implant materials with
      satisfactory anti-inflammatory and osteogenesis-promoting properties.

PMID- 30106515
TI  - Muscle Stem Cell Immunostaining.
AB  - Muscle stem cells (MuSCs) are essential for maintaining muscle homeostasis by
      providing progenitor cells for muscle regeneration after injury and in muscular
      diseases. MuSC properties dynamically change, reflecting physiology or
      pathological status. For instance, MuSCs are activated after muscle injury, but
      become exhausted in late stages of Duchenne Muscular Dystrophy (DMD) disease and
      senescent during aging. Therefore, characterization of MuSCs, including
      proliferation, activation, senescence, and apoptosis, etc., is very important in
      applying MuSC knowledge to regenerative medicine, such as in the treatment of DMD
      and to improve muscle function in aging. Here, we describe a detailed method for
      characterizing MuSCs in situ using immunostaining techniques in the mouse. This
      method can also be easily adapted to analyze other skeletal muscle properties.
      (c) 2018 by John Wiley & Sons, Inc.

PMID- 30106514
TI  - Bio-Orthogonally Crosslinked, In Situ Forming Corneal Stromal Tissue Substitute.
AB  - In this study, an in situ forming corneal stromal substitute based on collagen
      type I crosslinked by bio-orthogonal strain-promoted azide-alkyne cycloaddition
      (SPAAC) is presented. The crosslinked collagen gel has greater transparency
      compared to non-crosslinked collagen gels. The mechanical properties of the gels
      are controlled by changing functional group ratios and conjugated collagen
      concentrations. Higher concentrations of conjugated collagen yield enhances
      mechanical properties, where the storage modulus increases from 42.39 +/- 8.95 to
      112.03 +/- 3.94 Pa after SPAAC crosslinking. Encapsulated corneal keratocytes
      grow within the SPAAC-crosslinked gels and corneal keratinocytes are supported on
      top of the gel surfaces. SPAAC-crosslinked gels support more favorable and stable
      keratinocyte morphology on their surface compared to non-crosslinked gels likely
      as a result of more optimal substrate stiffness, gel integrity, and resistance to
      degradation. SPAAC-crosslinked collagen gels with and without encapsulated
      keratocytes applied to rabbit corneas in an organ culture model after keratectomy
      exhibit surface epithelialization with multilayered morphology. The novel in situ
      forming gel is a promising candidate for lamellar and defect reconstruction of
      corneal stromal tissue.

PMID- 30106516
TI  - Contraception Use Among Reproductive-Age Women with Rheumatic Diseases.
AB  - OBJECTIVE: To determine contraception use among a cohort of reproductive-age
      women (18-50 years) with rheumatic diseases. METHODS: We conducted a study of
      administrative data from a single, large medical center between years 2013 and
      2014. Women who had 1 of 21 rheumatic disease diagnoses and had at least 2
      outpatient rheumatology visits were included in this analysis. We used logistic
      regression analyses to evaluate adjusted associations between the use of
      prescription contraception, use of potentially fetotoxic medications, and visits
      with rheumatologists, primary care providers (PCP), and gynecologists. RESULTS:
      Of 2455 women in this sample, 32.1% used any prescription contraception, and 7.9%
      of women used highly effective prescription methods (intrauterine devices,
      implants, and surgical sterilization). Over 70% of women used at least one
      fetotoxic medication during the two-year study timeframe. Fetotoxic medication
      use was not associated with overall use of prescription contraception, but was
      associated with the use of highly effective contraceptive methods (aOR 2.26,
      95%CI: 1.44-3.54). Women who saw gynecologists or PCPs were more likely to use
      prescription contraception overall (aOR 3.35, 95%CI: 2.77-4.05 and aOR 1.43,
      95%CI: 1.18-1.73, respectively). Women who saw gynecologists were more likely to
      use highly versus moderately effective contraceptive methods (aOR 2.35, 1.41
      3.94). Rheumatology visits were not associated with use of prescription
      contraception in any models. CONCLUSIONS: This is the largest study to describe
      contraceptive usage among reproductive-age women with rheumatic diseases, and
      reveals low usage of prescription contraception. Urgent efforts are needed to
      improve contraceptive care and access, for some women with rheumatic diseases.
      This article is protected by copyright. All rights reserved.

PMID- 30106517
TI  - Profiling Interactome Networks with the HaloTag-NAPPA In Situ Protein Array.
AB  - Physical interactions between proteins and other molecules can be evaluated at a
      proteome scale using protein arrays, a type of high-throughput pulldown assay. We
      developed a modified in situ protein array known as the nucleic acid programmable
      protein assay (NAPPA) that allows the screening of thousands of open reading
      frames (ORFs) at a lower cost, with less labor, and in less time than
      conventional protein arrays. The HaloTag-NAPPA protein array can efficiently
      capture proteins expressed in situ on a glass slide using the Halo high-affinity
      capture tag. Here, we describe the fabrication of the array using publicly
      available resources and detection of protein-protein interactions (PPIs) that can
      be used to generate a protein interactome map. The Basic Protocol includes
      procedures for preparing the plasmid DNA spotted on glass slides, in situ protein
      expression, and PPI detection. The supporting protocols outline the construction
      of vectors and preparation of ORF clones. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30106518
TI  - Critical Assessment of the mdx Mouse with Ex Vivo Eccentric Contraction of the
      Diaphragm Muscle.
AB  - Muscle function and health progressively deteriorate during the progression of
      muscle dystrophies. The ability to objectively characterize muscle function and
      muscle damage is useful not only when comparing variants of dystrophy models, but
      also for characterizing the effects of interventions aiming to improve or halt
      the progressive decline of muscle function and muscle health. The protocols in
      this chapter describe the use of ex vivo eccentric contraction of the diaphragm
      muscle as a measure of muscle susceptibility to damage. Because muscle has a
      robust regenerative capacity, unhealthy muscle may be functionally close to
      normal; therefore, protocols for ex vivo characterization of muscle are often
      essential for assessing the effects of interventions. Additional methods that can
      be applied for assessment of dystrophic muscle are also highlighted. (c) 2018 by
      John Wiley & Sons, Inc.

PMID- 30106519
TI  - Bioinstructive Naringin-Loaded Micelles for Guiding Stem Cell
      Osteodifferentiation.
AB  - Naringin is a naturally occurring flavanone with recognized neuroprotective,
      cardioprotective, anti-inflammatory, and antiosteoporotic properties. Herein, the
      delivery of Naringin-loaded methoxy-poly(ethylene glycol)-maleimide-thiol-poly(l
      lactide) (mPEG?MS?PLA) diblock polymeric micelles to human adipose-derived stem
      cells (hASCs) with the aim to augment its pro-osteogenic effect in these cells is
      reported for the first time. The synthesis of the diblock copolymer is performed
      via Michael-type addition reaction between hydrophilic methoxy-poly(ethylene
      glycol)-maleimide (mPEG?MAL) and hydrophobic thiol-poly(l-lactide) (PLA?SH) and
      confirmed by 1 H NMR and attenuated total reflectance Fourier transformed
      infrared (ATR-FTIR) spectroscopy. The resulting mPEG?MS?PLA copolymer self
      assembles into monodispersed polymeric micelles (~84.4 +/- 2 nm) and presents a
      high Naringin encapsulation efficiency (87.8 +/- 4%), with a sustained release
      profile at physiological pH. Alongside, in vitro data reveal that upon
      internalization into hASC 2D cultures, Naringin nanomicellar formulations attain
      a higher pro-osteogenic effect than that of free drug. Notably, these bioactive
      carriers also induce superior osteopontin expression and increase matrix
      mineralization in these cells over free drug administration. Overall, such
      findings support for the first time the use of polymeric nanomicelles for
      Naringin delivery into hASCs as a valid approach for modulating stem cell
      osteogenic differentiation.

PMID- 30106520
TI  - The importance of hypoalbuminemia in peritoneal dialysis patients: Impact of
      gender.
AB  - BACKGROUND: High mortality in peritoneal dialysis (PD) patients is associated
      with the presence of nontraditional cardiovascular risk factors, such as
      malnutrition. However, hypoalbuminemia in patients undergoing PD may have gender
      dependent consequences. OBJECTIVES: The aim of the study was to evaluate the
      relationship between hypoalbuminemia, overhydration (OH), inflammation, and
      cardiovascular risk, depending on gender. MATERIAL AND METHODS: The group studied
      consisted of 54 PD patients: 26 male (mean age: 59 +/-19 years) and 28 female
      (mean age: 52 +/-15 years) patients. Serum albumin levels were measured routinely
      by the hospital central laboratory. The degree of OH was assessed by
      bioelectrical impedance analysis (BIA). Serum concentrations of C-reactive
      protein (CRP) and interleukin (IL)-6 were measured as inflammatory markers.
      Levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and
      troponin T (TnT) were used to assess cardiovascular risk. RESULTS: Median serum
      albumin concentration was 3.9 g/dL (3.6-4.2 g/dL). Both genders were comparable
      regarding most parameters except body weight (79 +/-16 kg vs 67 +/-16 kg; p =
      0.009), but no differences were observed in body mass index (BMI) (26.3 +/-5.0
      kg/m2 vs 26.2 +/-5.9 kg/m2; non significant (NS)). There was also no difference
      in the prevalence of hypoalbuminemia between female and male PD patients (23% vs
      21%; NS). In females, low serum albumin concentrations were associated with OH,
      inflammation and cardiovascular risk, while in males serum albumin levels
      correlated with the parameters of dialysis and cardiovascular risk. CONCLUSIONS:
      The impact of hypoalbuminemia may be gender-dependent. It seems that
      hypoalbuminemia is more important for female patients. It is also possible that
      different mechanisms regulate serum albumin concentration in female and male PD
      patients.

PMID- 30106521
TI  - Patients' willingness to pay for dental services in a population with limited
      restorative services.
AB  - OBJECTIVES: To determine and compare patients' willingness-to-pay (WTP) for tooth
      extraction and filling services in Tanzania and to assess the socio-demographic
      factors that are associated with such valuations. METHODS: Contingent valuation
      survey utilizing an open-ended willingness-to-pay format was administered among
      1522 outpatients in four regional hospitals in Tanzania. WTP for extraction and
      tooth filling services for various tooth categories were determined and compared
      using Mann-Whitney and Kruskal-Wallis tests. The association of WTP values with
      socio-demographic background factors was assessed using multiple regression
      analysis. RESULTS: The mean WTP amounts for tooth filling were Tanzania shillings
      (Tshs) 7,398 (3.4 US$) and Tshs 7,726 (3.5 US$) for anterior and posterior teeth
      respectively. The mean WTP for tooth filling services was lower than the average
      charged fees in dental facilities. The mean WTP amounts for tooth extraction were
      Tshs 5,448 (2.5 US$) and Tshs 6,188 (2.8 US$) for anterior and posterior teeth
      respectively. WTP amounts were shown to vary by age, income, outpatient status
      and previous experience with the dental services. Belonging in youngest age group
      (18-24 years) and having a high-income level was associated with increased odds
      for high WTP valuations irrespective of tooth and treatment types. CONCLUSIONS:
      WTP reveals a preference for tooth filling rather than extraction services in
      this population. More studies are needed to address the discrepancy between the
      stated preferences and utilization patterns for dental services.

PMID- 30106522
TI  - Depressive symptoms and untreated coronal dental caries among adults ages 21-64
      years, NHANES 2013-2014.
AB  - BACKGROUND: Depression has been linked to poor oral health among patients seeking
      dental care. However, systematic research on the relationship between depressive
      symptoms and oral health is limited. OBJECTIVE: To examine the association of
      depressive symptoms with untreated dental caries among adults aged 21-64 years.
      BASIC RESEARCH DESIGN: Cross-sectional secondary analysis. SETTING: The data were
      extracted national data collected in the United States (2013-2014 National Health
      Nutrition and Examination Survey). PARTICIPANTS: The sample consisted of 3,127
      non-institutionalized civilians. MAIN OUTCOME MEASURE: Untreated coronal dental
      caries (yes, no) was the key outcome variable. Depressive symptom categories
      (none, moderate, and severe) were derived from the Patient Health Questionnaire-9
      Depression Scale. RESULTS: In the study sample, 33.4% of adults had untreated
      coronal dental caries. Most participants (77.9%) did not report depressive
      symptoms; 13.9% had mild and 8.2% had moderate or severe depressive symptoms. In
      unadjusted analyses, individuals with mild (Odds Ratio = 1.62 [95% CI: 1.26,
      2.08] and moderate/severe depressive symptoms (Odds Ratio = 2.70 [95% CI: 1.81,
      4.02]) were more likely to have untreated coronal caries as compared with
      individuals without depressive symptoms. When sex, race, age, education, family
      income-to-poverty ratio, dental visits, history of previous dental restorations,
      health insurance, and smoking were included into the model, the associations were
      no longer statistically significant (1.27 [95% CI: 0.96, 1.69] and 1.61 [95% CI:
      0.95, 2.73], respectively). CONCLUSION: The relationship between depressive
      symptoms and untreated coronal dental caries failed to remain significant after
      the addition of tobacco usage in the analysis.

PMID- 30106523
TI  - School-based oral health education increases caries inequalities.
AB  - OBJECTIVE: To evaluate the effect of one and half years of an oral health
      promotion program in primary schools. DESIGN: A cluster-randomized controlled
      trial. PARTICIPANTS: 740 students aged 9-12 years (48% female) recruited from the
      fifth grade of 18 different primary schools in West Pomerania, Germany. METHODS:
      General and oral health education was provided to the teachers in the
      intervention schools, which they conveyed to their students. No additional
      measures were conducted in the control schools. Medical and dental school
      examinations, as well as questionnaires for the students and their parents were
      conducted at baseline and follow-up. Data were analysed using Poisson regression
      models. RESULTS: A significant incident rate ratio between caries increment was
      found, with a 35% higher risk in the control group. However, parents'
      socioeconomic characteristics modified the effect of the program on their
      children, as high socio-economic status in the intervention group was associated
      with 94% reduction in the incidence risk ratio (p ? 0.001). CONCLUSIONS: The
      program was effective in improving dental health among students with higher socio
      economic status. No preventive effect could be found in low socio-economic status
      groups.

PMID- 30106525
TI  - A two-step stannous fluoride dentifrice and whitening gel sequence.

PMID- 30106526
TI  - Clinical evidence on a unique two-step stannous fluoride dentifrice and whitening
      gel sequence.
AB  - PURPOSE: Recently, a unique two-step product was introduced that includes
      sequential use of a novel 0.454% stannous fluoride dentifrice followed by a 3%
      hydrogen peroxide whitening gel. The technology targeted advanced gingival health
      benefits plus esthetic benefits such as tooth whitening. The two-step sequence
      has unique brushing instructions to maximize the efficacy of each step; the
      stannous fluoride dentifrice is used for 1 minute of brushing followed by 1
      minute of brushing with the hydrogen peroxide gel. This two-step sequence has
      been studied in numerous clinical trials over a series of years. This
      comprehensive program included different populations and sites, endpoints and
      time points, with responses measured versus different positive and negative
      research controls. A total of six clinical trials are reported herein. Outcomes
      from this research program demonstrate the significant gingival health efficacy
      of the two-step product, providing therapeutic efficacy comparable to
      chlorhexidine, and its positive impact on plaque, tooth stain and breath odor.
      CLINICAL SIGNIFICANCE: This unique dentifrice/gel sequence delivers a combination
      of advanced gingivitis efficacy with significant stain reduction - benefits that
      will positively impact oral health as well as patient compliance.

PMID- 30106524
TI  - Fluoride content of toothpastes available in South Africa.
AB  - : A high dental caries burden coupled with a lack of water or salt fluoridation
      make it imperative that toothpastes available to the South African consumer
      demonstrate adequate potential for caries control and contain between 1000ppm and
      1500ppm total fluoride (TF), with at least 1000ppm F in free available/soluble
      form. METHODS: The objective was to determine TF, total soluble fluoride (TSF)
      and insoluble fluoride (IF) concentrations in 22 fluoride toothpastes
      commercially available in South Africa. Samples were purchased from a major
      pharmaceutical and food retailer located in the two metropolitan areas in South
      Africa. TF and TSF concentrations were determined potentiometrically, in
      quadruplicate, following acid hydrolysis of the samples using a calibrated
      Combination Fluoride Ion Selective Electrode. IF was calculated by subtracting
      TSF from TF. RESULTS: Although TF content was found to be statistically
      significantly lower than manufacturer declaration (3.2x10-7; p<=0.05), 77.3% of
      the samples still contained adequate free, available/soluble F levels. Relative
      mean TSF content for toothpastes formulated with a calcium-based abrasive was 85%
      (sd +/-14.5; n=6) as opposed to 98.6% (sd +/-2.6; n=16) for those containing
      silica. CONCLUSIONS: The total fluoride concentration of all the toothpastes was
      lower than that declared by the manufacturers, with one in four having TSF
      concentrations of less than 1000ppm F. The relative TSF concentrations for the
      calcium-containing toothpastes were lower than for the silica-based products,
      reducing their preventive and protective potential. The results call for
      strengthened regulation and quality control of fluoride toothpastes in South
      Africa, as well as international efforts to improve related norms.

PMID- 30106527
TI  - Initial evidence of two-step dentifrice/gel sequence effects on health: Outcomes
      from three randomized controlled trials.
AB  - PURPOSE: Health-related outcomes from three randomized controlled trials
      represented the initial research on the feasibility of novel, sequential oral
      hygiene with a stannous fluoride (SnF2) dentifrice then hydrogen peroxide (H2O2)
      whitening gel. METHODS: One crossover and two parallel clinical trials were
      conducted independently. Objectives varied, with individual studies assessing
      short, intermediate or longer-term outcomes from breath, dental plaque or
      gingivitis, respectively. Treatments were randomly assigned, and blinded test
      kits were dispensed containing either: 1) a two-step 0.454% SnF2 dentifrice and
      then a 3% H2O2 whitening gel sequence and instructions specifying 1+1 minute
      sequential brushing (experimental); or 2) 0.76% sodium monofluorophosphate
      dentifrice (Colgate Cavity Protection) and instructions for twice daily use
      (control). Standard methods were used to measure efficacy (volatile sulfur
      compounds, plaque area coverage or gingival bleeding) and safety (clinical
      examination and interview), and to compare treatment responses. RESULTS: Overall,
      165 subjects participated in the three trials. Relative to baseline, only the
      experimental group exhibited significant (P< 0.05) improvements at initial and
      subsequent timepoints in each trial. Between-group comparisons showed significant
      (P< 0.05) 30-45% reductions in breath malodor (VSC), plaque (area%) and
      gingivitis (bleeding sites) favoring the experimental group. Adverse event
      occurrences were infrequent, mild in severity, and unrelated to dropout. CLINICAL
      SIGNIFICANCE: Important health-related outcomes from three initial clinical
      trials established the feasibility of sequential brushing with a two-step 0.454%
      SnF2 dentifrice and then a 3% H2O2 whitening gel.

PMID- 30106528
TI  - Randomized controlled trial evaluating concurrent gingivitis and stain effects of
      a two-step dentifrice/gel sequence.
AB  - PURPOSE: A randomized controlled trial was conducted to evaluate the clinical
      efficacy of a two-step dentifrice/whitening gel oral hygiene sequence on natural
      gingivitis and extrinsic stain. METHODS: The population consisted of healthy
      adults with clinical evidence of gingivitis and extrinsic stain. Consent,
      demographic information and clinical measurements were collected, after which
      subjects were randomized to treatment. Eligible subjects were dispensed blinded
      test kits containing over-labeled two-step 0.454% SnF2 dentifrice then 3% H2O2
      whitening gel sequence or a regular 0.76% NaMFP dentifrice control (Colgate
      Cavity Protection), plus a regular soft manual toothbrush and instructions for
      use. Efficacy was assessed blind-to-treatment using the Gingivitis Bleeding Index
      (GBI) measured whole-mouth and the composite Lobene Stain Index (LSI) measured on
      the anterior dentition. Treatments were compared at Week 1 and Week 3 versus
      baseline for DeltaGBI and DeltaLSI using a two-sided 5% level of significance.
      RESULTS: A total of 61 subjects with a mean (SD) age of 33.4 (12.0) years were
      enrolled. Overall baseline means (SD) were 0.16 (0.05) for GBI and 1.30 (0.94)
      for LSI. After 1 week, only the two-step 0.454% SnF2 dentifrice then 3% H2 O2
      whitening gel sequence demonstrated significant (P< 0.0001) reductions in both
      gingivitis and stain. Adjusted means for the changes with the dentifrice/gel
      sequence and control were -0.055 and -0.001 for DeltaGBI, and -0.619 and -0.095
      for DeltaLSI, with groups differing significantly (P< 0.0001) on gingivitis and
      stain improvement. Outcomes at Week 3 were generally similar, with groups
      differing on bleeding and stain. Treatments were generally well-tolerated.
      CLINICAL SIGNIFICANCE: In a randomized controlled trial, use of a two-step 0.454%
      SnF2 dentifrice then 3% H2 O2 whitening gel sequence yielded concurrent
      improvements in gingivitis and stain compared to regular oral hygiene.

PMID- 30106529
TI  - Post-prophylaxis gingivitis prevention with two-step stannous fluoride dentifrice
      plus whitening gel sequence or chlorhexidine gluconate mouthrinse.
AB  - PURPOSE: To assess use of a two-step dentifrice/gel sequence versus chlorhexidine
      gluconate mouthrinse on gingivitis prevention after dental prophylaxis. METHODS:
      A 12-week, randomized controlled trial was conducted to compare the effectiveness
      and safety of a two-step dentifrice/gel sequence to a positive control in healthy
      adults with established gingivitis. After informed consent, gingivitis and stain
      levels were assessed by clinical examination. Eligible subjects received a dental
      prophylaxis and were randomly assigned to twice daily unsupervised use of either
      (1) two-step oral hygiene sequence:0.454% stannous fluoride dentifrice followed
      by 3.0% hydrogen peroxide whitening gel for the test group; or (2) 0.12%
      chlorhexidine gluconate oral rinse and 0.76% sodium monofluorophosphate
      dentifrice for the control group. Clinical measurements of gingivitis bleeding
      sites and tooth stain area/intensity were collected after 4, 8 and 12 weeks use,
      while safety was assessed via clinical examination and oral status interview of
      the subjects. RESULTS: A total of 44 subjects were enrolled and 35 completed the
      12-week study. At baseline, bleeding sites ranged from 10-33. After prophylaxis
      and assigned treatment, both groups exhibited significant (P<= 0.0001) reductions
      in bleeding sites. Responses were directionally better in the two-step sequence
      at all post-baseline timepoints, with groups differing significantly (P < 0.05)
      at Week 8. Tooth stain measurements demonstrated that the two-step dentifrice/gel
      sequence did not contribute to any significant (P> 0.13) stain accumulation. In
      contrast, stain accumulation was evident (P< 0.003) in the chlorhexidine group
      beginning at the Week 4 visit. Adverse events were more common in the positive
      control, and contributed to early termination. CLINICAL SIGNIFICANCE: Twice daily
      use of a two-step stannous fluoride dentifrice and peroxide whitening gel
      sequence after prophylaxis provided comparable or superior gingivitis benefits to
      chlorhexidine gluconate rinse without the concomitant side effect of staining.

PMID- 30106530
TI  - Safety and effectiveness of a two-step dentifrice/gel sequence with medication
      associated hyposalivation: A randomized controlled trial in a vulnerable
      population.
AB  - PURPOSE: A randomized controlled trial was conducted to evaluate the safety and
      effectiveness of a two-step dentifrice/gel oral hygiene sequence in a vulnerable
      population. METHODS: Prior to the research, institutional review was obtained for
      the protocol, consent and advertising. The study targeted adults with medication
      associated xerostomia, because of the plaque accumulation and possible oral
      safety risks seen in this population. Eligible subjects with a medication history
      and measured hyposalivation were randomly assigned to one of two oral hygiene
      groups:(1) a two-step 0.454% SnF2 dentifrice and 3% H2O2 gel sequence or (2) a
      regular anticavity toothpaste control. Test products were dispensed with a
      regular manual brush in blinded over-labeled kits with usage instructions.
      Subjects were evaluated at baseline and after 2 and 6 weeks of test product use.
      Safety was assessed as adverse events from clinical examination and interview.
      Digital plaque image analysis of the anterior facial teeth measured fluorescein
      disclosed daytime plaque levels, and unstimulated saliva was collected over a 5
      minute period in pre-weighed vials. RESULTS: A total of 49 subjects ranging from
      31-80 years of age (53% female) were enrolled, and 45 completed Week 6. Only the
      two-step dentifrice and gel sequence differed significantly (P< 0.005) from
      baseline on daytime plaque coverage, and salivary flow increased significantly
      (P= 0.033) in that group as well. Between-group comparisons for daytime plaque
      favored the two-step sequence with 41-46% improvements in plaque control. At Week
      6, adjusted daytime plaque means (SE) were 5.9 (0.7) and 10.0 (1.1) for the two
      step and control groups, respectively (P< 0.004). Adverse events were mild in
      severity, groups differed significantly (P= 0.02) on occurrence, and events did
      not contribute to dropout. CLINICAL SIGNIFICANCE: In a randomized controlled
      trial among a vulnerable population, use of an oral hygiene sequence comprised of
      stannous fluoride dentifrice and a hydrogen peroxide whitening gel improved daily
      plaque control without adversely impacting salivary flow or oral health.

PMID- 30106531
TI  - A 6-month clinical evaluation of a high frequency sonic toothbrush in comparison
      with an oscillating-rotating power toothbrush and a traditional sonic toothbrush
      in reducing gingivitis and plaque.
AB  - PURPOSE: To compare the 6-month clinical efficacy of a novel high frequency sonic
      power toothbrush (A) with an oscillating-rotating (O-R) power toothbrush (B) and
      a traditional sonic toothbrush (C) in reducing plaque and gingivitis. METHODS:
      This was a single-center, randomized, examiner-blind, parallel group design
      consisting of two two-treatment sub-trials. Gingivitis was assessed using the
      Modified Gingival Index (MGI) and Gingival Bleeding Index (GBI). Plaque was
      assessed using the Rustogi Modified Navy Plaque Index (RMNPI) at Baseline, Month
      3, and Month 6. Statistical analysis between A versus B and A versus C were
      evaluated. Data were analyzed using an ANCOVA with the baseline score as the
      covariate. RESULTS: In total, 120 subjects (40 per group) were randomized to
      treatments and 119 subjects completed the study. All power toothbrushes provided
      statistically significant reductions in gingivitis and plaque relative to
      Baseline (P< 0.001). Reductions in MGI and GBI scores were not statistically
      significantly different between A and B at Months 3 and 6. While A had
      statistically significant 20.1% and 29.0% greater reductions in total RMNPI and
      interproximal RMNPI respectively, compared to B at Month 6 (P< 0.05). Reductions
      in gingivitis and plaque indices were not statistically significantly different
      between A (41,000 oscillations/minute) and C (31,000 oscillations/minute) at
      Month 3. Compared to C, A demonstrated 14.0% and 14.5% greater reductions in MGI
      and GBI respectively, and 26.0% greater reduction in interproximal RMNPI versus
      baseline at Month 6 (P< 0.05). No adverse events were reported for the power
      toothbrushes. CLINICAL SIGNIFICANCE: The new high frequency sonic power
      toothbrush was not significantly different from the oscillating-rotating power
      toothbrush in gingivitis reduction while it demonstrated statistically
      significantly greater reductions in plaque. The new high frequency sonic power
      toothbrush was significantly more efficacious than the traditional sonic
      toothbrush in reducing plaque and gingivitis after long term use.

PMID- 30106532
TI  - Effect of desensitizing toothpastes on dentin erosive wear and tubule occlusion.
      An in situ study.
AB  - PURPOSE: To evaluate the effect of desensitizing dentifrices on dentin wear and
      tubule occlusion using a three-phase, single blind, crossover in situ trial.
      METHODS: The dentifrices containing Arginine and calcium carbonate (1,450 ppmF)
      and Novamin, (~1,426 ppmF) were tested in two conditions: A: abrasion and B:
      erosion/abrasion. A dentifrice without desensitizing agents was used as control
      (1,450 ppmF). In each study phase, 10 volunteers used intra-oral appliances
      containing dentin specimens (pre-treated with EDTA, to simulate hypersensitive
      dentin), which were either submitted to erosion with a cola-like drink (pH 2.6),
      4*/day (2 minutes), followed by toothbrushing, using electric toothbrushes, with
      standard pressure (2*/ day, 5 seconds), or toothbrushing only. Dentin surface
      loss (SL, in um) was determined with optical profilometry at the 3rd and 5th days
      of cycling. Dentin surface was analyzed with environmental scanning electron
      microscopy (ESEM), post EDTA and post cycling, and the dentin tubules were
      counted using Image J software. Data were statistically analyzed (alpha= 0.05).
      RESULTS: For condition A and B, there were no significant differences in SL among
      toothpastes in both experimental times. There were also no significant
      differences between times within groups. For ESEM, in A, Toothpaste with Novamin
      was the only dentifrice that showed significantly less opened tubules post
      cycling than post EDTA. In B, Toothpaste with Novamin and control toothpaste
      presented less opened tubules post cycling. In conclusion, toothbrushing with the
      tested dentifrices promoted similar levels of dentin loss; however, for tubule
      occlusion, the toothpaste with Novamin was the only toothpaste effective for both
      conditions, abrasion and erosion/abrasion. CLINICAL SIGNIFICANCE: Ideally,
      desensitizing dentifrices should promote obliteration of the dentin tubules or
      nerve desensitization, without further contributing to the progression of dentin
      wear.

PMID- 30106533
TI  - Subgingival uptake and retention of stannous fluoride from dentifrice: Gingival
      crevicular fluid concentrations in sulci post-brushing.
AB  - PURPOSE: To examine the delivery of stannous fluoride to subgingival sulci
      following toothpaste use in a clinical population. METHODS: This was a
      controlled, single-site study. 23 subjects with at least 20 dental pockets, 2-4
      mm with bleeding, who had not used a stannous fluoride dentifrice in the last 3
      months were enrolled. After a 2-week washout period, 20 subjects returned for a
      baseline visit. They were instructed to refrain from brushing the night before
      the baseline visit. GCF samples were taken from up to 10 sites identified as
      sampling sites. Subjects were then given a 0.454% stannous fluoride dentifrice
      and soft manual toothbrush and asked to brush for 1 minute. 30 minutes after
      brushing, GCF was re-sampled. Subjects continued using the stannous fluoride
      dentifrice and soft manual toothbrush at home, twice daily for 2 weeks, in place
      of their usual hygiene products. At Days 1 and 14, subjects returned to the site,
      and 12 hours post-brushing GCF samples were taken. The samples were analyzed by
      ICP-MS (inductively coupled plasma mass spectrometry). A Wilcoxon signed-rank
      test was performed to determine the difference between post-baseline visits and
      baseline. Statistical tests were 2-sided using a 5% significance level. RESULTS:
      20 subjects completed the trial. Significant levels of tin, a marker for stannous
      fluoride, were detected 30 minutes after brushing at sampling sites of 2-4 mm.
      The median tin level in gingival crevicular fluid (GCF) was 24.59 ng/ul, which
      was highly significant versus baseline (P< 0.0001). Tin levels sampled in GCF 12
      hours after brushing on Days 1 and 14 were highly significant versus Baseline (P<
      0.0001), showing an increasing trend with continued use. CLINICAL SIGNIFICANCE:
      Stannous fluoride was found to penetrate sampling sites from 2-4 mm and was
      retained for 12 hours. Subgingival uptake and retention of stannous fluoride
      following toothbrushing may play a role in detoxification effects on microbial
      biofilms and may contribute to the therapeutic efficacy of stannous fluoride
      dentifrices in promoting gingival health.

PMID- 30106534
TI  - Randomized clinical trial to determine if changes in dentin tubule occlusion
      visualized by SEM of replica impressions correlate with pain scores.
AB  - PURPOSE: To quantify dentin tubule occlusion and correlate this with pain
      reduction in vivo. METHODS: This was a single-center, randomized two treatment,
      examiner-blind, parallel study. 20 participants with confirmed dentin
      hypersensitivity (DH) were evaluated by Schiff Air Blast, VAS Air Blast and
      replica impression of the tooth surface to visualize tubule occlusion at baseline
      and following 4-week twice daily use of either an occluding toothpaste (8%
      strontium acetate, 1,040 ppm fluoride) or a non-occluding toothpaste (1,450 ppm
      fluoride). RESULTS: Both treatments increased tubule occlusion significantly from
      baseline to 4 weeks (P= 0.01) with significant decreases in pain score only seen
      with the occluding toothpaste (Schiff, P= 0.01; VAS, P= 0.01). Schiff pain score
      after 4 weeks was markedly reduced following treatment with the occluding
      toothpaste as compared to the non-occluding toothpaste, (P= 0.05) with no
      significant differences between the pastes for occlusion score or patient
      reported VAS, although the scores favored the occluding toothpaste. CLINICAL
      SIGNIFICANCE: Occlusion scores as obtained by replica impression techniques with
      SEM imaging correlate significantly with DH pain scores confirming proof of
      concept. With further refinement, this technique could be used to accurately
      quantify tubule occlusion in vivo and the associated pain reduction achieved by
      occluding toothpastes.

PMID- 30106535
TI  - Efficacy of ibuprofen and codeine + paracetamol to reduce immediate bleaching
      sensitivity caused by in-office tooth bleaching: A randomized, controlled, double
      blind clinical trial.
AB  - PURPOSE: To evaluate (1) the efficacy of Ibuprofen and codeine + paracetamol to
      control immediate bleaching sensitivity caused by in-office tooth bleaching
      performed with 35% hydrogen peroxide, and (2) tooth shade change caused by 35%
      hydrogen peroxide. METHODS: In this randomized, controlled and double blind
      clinical trial, 60 volunteers were divided into three treatment groups: 400 mg
      placebo (PL)(n=20), 400 mg ibuprofen (IB)(n=20), or 30 mg codeine + 500 mg
      paracetamol (CP)(n=20). The volunteers were submitted to two bleaching sessions
      with 35% hydrogen peroxide in 2 applications of 20 minutes each. In both
      sessions, the medication was given to the volunteers 1 hour before the bleaching
      procedure. The sensitivity values were obtained with the analogic visual pain
      scale. Tooth shade was assessed before and after bleaching. Statistical analysis
      was done through the one-way ANOVA and Tukey post-hoc tests. RESULTS: For
      bleaching sensitivity, there were statistically significant differences among the
      medications (P< 0.01). The lowest sensitivity means were found in the CP group
      (PL:4.7 = IB:4.8 > CP:1.0). In regards to tooth shade, participant's teeth were
      statistically significantly lighter after bleaching than before bleaching (P<
      0.01), with no statistically significant difference between the medications (P<
      0.05). CLINICAL SIGNIFICANCE: The use of codeine + paracetamol 1 hour before in
      office tooth bleaching can drastically reduce immediate sensitivity.

PMID- 30106536
TI  - Surface treatments to improve the repair of acrylic and bis-acryl provisional
      materials.
AB  - PURPOSE: To evaluate the in vitro effects of the Composite Primer and different
      surface treatments on the shear bond strength (SBS) of acrylic and bis-acryl
      repairs with resin composite (RC). METHODS: Acrylic (Alike) and bis-acryl
      (Protemp 4) blocks were prepared. Surface roughness was standardized (0.16 um)
      and grit blasting was applied to half of the samples. Blocks were divided
      randomly into groups according to surface treatment [methyl methacrylate monomer
      (MMA) for 180 seconds or bonding agents (Composite Primer and Scotchbond Multi
      Purpose), applied alone or following MMA]. Two consistencies of RC [ regular
      (Filtek Z350XT and Solare composite) or flowable (Filtek Z350XT flowable and G
      aenial flowable composite) ] were used to test bond repair. Cylinders (2 mm
      diameter) of each RC (n= 10/group) were attached to the block surface, and SBS
      was measured using a universal testing machine at 0.5 mm/minute. Failure
      (adhesive, cohesive or mixed) was assessed under *3.5 magnification. SBS data
      were analyzed using factorial ANOVA, followed by Tukey post-hoc, and Weibull
      moduli estimation (alpha = 0.05). RESULTS: The highest SBS, Weibull modulus (m)
      and scale parameter (sigma0) were found in combined use of MMA and bonding agents
      (P< 0.001), regardless of the substrate, RC consistency or brand. The use of the
      Composite Primer and flowable RC also increased SBS (P< 0.001). Significant
      interaction between surface treatment and RC consistency was observed for the
      PMMA substrate (P< 0.001). Sandblasting did not influence SBS (P> 0.05). Adhesive
      failure was most prevalent (93.5%) and SBS values were significantly higher in
      mixed fractures (19.2+/- 3.8 MPa) compared to the adhesive ones (9.7+/- 6.0 MPa)
      (P< 0.001). No cohesive fracture was observed. CLINICAL SIGNIFICANCE: Composite
      Primer improved the adhesion of acrylic and bis-acryl repairs, especially when a
      flowable composite was used. When such product is not available, the combined use
      of MMA and a bonding agent is necessary, increasing the number of clinical steps,
      cost, and time required.

PMID- 30106538
TI  - Effect of different mouthwashes on discoloration of plaque-free tooth surfaces.
AB  - PURPOSE: To evaluate the tooth discoloration effect of the daily use protocol of
      six different mouthrinses. METHODS: 70 extracted caries-free central incisors
      were divided into seven groups (n=10/per group) : Group 1: Curasept Anti
      Discoloration System; Group 2: CB12; Group 3: Listerine Zero; Group 4: Listerine
      Cool Mint; Group 5: Colgate Plax; Group 6: Kloroben. The teeth were exposed to
      the mouthrinse for 2 minutes daily for 3 weeks. Color measurement was performed
      four times: at the beginning of the study, and after 1, 2 and 3 weeks, with a
      digital spectrophotometer (Vita Easyshade Advanced). Color changes (DeltaE) were
      calculated and ANOVA and post hoc Tukey's test were used for statistical
      analysis. RESULTS: Although there was no statistically significant difference
      between the Colgate Plax and control groups, both groups had a significant
      difference from the other groups within all DeltaE1, DeltaE2 and DeltaE3 values.
      CLINICAL SIGNIFICANCE: Among the mouthrinses tested, Listerine Cool Mint group
      exhibited the most tooth discoloration, while Colgate Plax demonstrated the least
      noticeable color change.

PMID- 30106537
TI  - Effect of thermal cycling on fracture toughness of CAD/CAM materials.
AB  - PURPOSE: To compare the fracture toughness of four different CAD/CAM materials,
      (VM) Vitablocs Mark II, (IP) IPS e.max CAD, (LU) LAVA Ultimate, and (VE) Vita
      Enamic under long thermocycling conditions. METHODS: Each type of ceramic block
      was sectioned into beams (n=9) with dimensions of 14*3*2.5 mm (L * W * H). All
      four ceramics were submitted to different conditions: the desiccator or distilled
      water, each for 7 days. The third and fourth conditions involved the specimens
      being submitted to 60,000 and 120,000 thermocycles in water respectively. The
      dwelling time was 52 seconds at 5 degrees  and 55 degrees C. A three-point bend
      test with a universal loading machine on notched samples was per-formed.
      Furthermore, a fractographic analyses was made by scanning electron microscopy
      (SEM) to determine if any of these conditions influenced the type of fracture.
      Data were analyzed by two-way ANOVA (alpha= 0.05). RESULTS: A significant
      difference in fracture toughness (P< 0.05) was found among the groups; IP (4.20+/
      1.23) had the highest value followed by VE (2.02+/-0.39), which did not have a
      statistically significant difference from LU (1.96+/-0.42). The lower value and
      statistical difference for VM was 1.52+/-0.35. The ceramics performed better
      after they were hydrated, while the polymer-based materials had the fracture
      toughness means decreased after the thermocycles. CLINICAL SIGNIFICANCE: A
      significant difference in fracture toughness (P<0.05) was found among the groups;
      IP had the highest value followed by VE, which was not statistically
      significantly different from LU. The ceramics performed better after they were
      hydrated, while the polymer-based materials had fracture toughness means
      decreased after thermocycling.

PMID- 30106539
TI  - Clinical effects of stannous fluoride dentifrice in reducing plaque microbial
      virulence III: Lipopolysaccharide and TLR2 reporter cell gene activation.
AB  - PURPOSE: This study expanded the analysis of subgingival dental plaques from
      previous research to include the evaluation of cohort, site and treatment effects
      on chemically measured endotoxin and activation of Toll-like receptor (TLR) based
      gene expression in two additional reporter cell lines: a TLR2 specific cell line
      and a THP-1 (multi TLR reporter) cell line. METHODS: Participants from high and
      low bleeding cohorts were sampled at baseline for both supra and subgingival
      dental plaque at both healthy as well as clinically diseased sites and then
      provided with intervention hygiene products including a stabilized SnF2
      dentifrice and a new soft bristle manual toothbrush. Following 2 and 4 weeks of
      assigned dentifrice use, participants returned for a re-evaluation of gingival
      inflammation and bleeding and repeat samplings of dental plaque. Subgingival
      sampled plaques were chemically analyzed for endotoxin concentration using a
      Thermo Scientific Pierce LAL chromogenic endotoxin quantitation kit. Samples were
      also used for inoculation of two reporter cell assays (an HEK293 TLR2 reporter
      cell line and a THP-1 monocyte cell line). Reporter cell activation was analyzed
      via luminescence changes of secreted embryonic alkaline phosphatase. RESULTS: The
      endotoxin content of subgingival plaque could be measured directly with dye
      assays and plaque isolates activated gene expression in both TLR reporter cell
      lines. Higher disease cohorts and sites with gingival inflammation generally
      showed more endotoxins and higher levels of plaque virulence as compared to low
      disease cohorts or plaque sampled from clinically healthy sites. SnF2 dentifrice
      treatment was associated with broad scale reductions in endotoxin content and
      virulence potentiation properties of dental plaque samples collected
      subgingivally from patients. CLINICAL SIGNIFICANCE: These results collectively
      support the use of dye or various reporter cell lines in the characterization of
      plaque virulence in diseased populations and as a potential route for analysis in
      clinical evaluations of treatment interventions. Subgingival plaque
      'detoxification' including effects on microbial pathogenicity as well as
      metabolic activity may be considered important mechanisms contributing to
      clinical benefits of SnF2 dentifrice.

PMID- 30106540
TI  - Protective effects of methanol extract of Plukenetia conophora seeds and 4H-Pyran
      4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl on the reproductive function of male
      Wistar rats treated with cadmium chloride.
AB  - OBJECTIVES: Male infertility caused by exposure to heavy metals is a current
      global issue. Exposure to cadmium chloride (CdCl2) negatively affects the male
      reproductive system. Many infertile people, especially in developing countries,
      resort to folkloric treatment. Plukenetia conophora is used in Nigerian folk
      medicine to promote fertility. This study investigated the effects of Plukenetia
      conophora (PC) and 4H-Pyran-4-One 2,3-Dihydro-3,5-Dihydroxy-6-Methyl (DDMP) on
      Wistar rats with cadmium chloride-induced testicular damage. METHODS: Forty-two
      male Wistar rats (150-190g) were divided into seven groups (n=6) and treated
      daily for 54 days as follows: Controls (normal saline); CdCl2 (2mg/kg single IP
      dose); CdCl2 + 200 mg/kg vitamin E; CdCl2 + 100 or 200 mg/kg PC; and CdCl2 + 25
      or 50 mg/kg DDMP. The rats were sacrificed 55 days after the start of the study;
      Samples were collected for analysis. Biochemical parameters malondialdehyde,
      nitric oxide, antioxidant enzymes, and proton pumps were measured by
      spectrophotometry. Reproductive hormones were measured using ELISA. Data were
      analysed using ANOVA and differences in mean values were considered significant
      at p<0.05. RESULTS: Significant increases in sperm count, motility, and viability
      were observed in the groups given CdCl2+Vitamin E, CdCl2+PC or CdCl2+DDMP as
      compared with the CdCl2 group. Malondialdehyde and nitric oxide levels in the
      groups treated with CdCl2+PC or CdCl2+DDMP decreased significantly when compared
      with the group given CdCl2. Significant increases were observed in antioxidant
      enzymes, proton pump, and testosterone in the groups treated with CdCl2+PC or
      CdCl2+DDMP, respectively. CONCLUSION: Plukenetia conophora alleviated male
      reproductive toxicity induced by cadmium chloride in Wistar rats. 4H-Pyran-4-One
      2,3-Dihydro-3,5-Dihydroxy-6-Methyl present in Plukenetia conophora may be
      responsible for the ameliorative effects.

PMID- 30106541
TI  - The effect of early coasting on blastocyst development and outcome following
      blastocyst transfer in IVF/ICSI programme.
AB  - OBJECTIVE: Coasting is a well-known strategy to decrease severity of Ovarian
      Hyperstimulation Syndrome (OHSS). The purpose of this study is to assess the
      effect of Coasting on blastocyst development and subsequent clinical outcome
      following exclusive blastocyst transfer. METHODS: We conducted an observational
      cohort study of patients having blastocyst transfer following IVF/ICSI treatment.
      Patients undergoing IVF/ICSI cycles were included in the study. Patients at risk
      of OHSS were coasted. Outcome following exclusive blastocyst transfer was
      compared between coasted and non-coasted groups. The main outcome measures were
      the rate of blastocyst development and live birth rates in coasted and non
      coasted cycles. Within coasted cycles, outcome was further analysed based on
      coasting duration and serum estradiol (E2) drop (difference between peak E2 and
      E2 on day of HCG). RESULTS: A total of 166 coasted cycles and 656 non-coasted
      cycles had blastocyst transfer. Blastocyst development (45.97% vs. 48.6%) and
      live birth rates (45.18% vs. 43.44%) were not significantly different between
      coasted and non-coasted cycles. The overall clinical pregnancy (54.21% vs.
      49.08%) and implantation rates (43.95% vs. 39.54%) following blastocyst transfer
      in coasted cycles were not significantly different from those of non-coasted
      cycles. CONCLUSION: Coasting duration up to 6 days and drop in serum E2 levels
      did not compromise blastocyst development, implantation, clinical pregnancy or
      live birth rates. We conclude that coasting with subsequent blastocyst transfer
      can be used as an effective strategy in patients at risk of OHSS with no
      detrimental effects on blastocyst development or live birth outcome.

PMID- 30106543
TI  - Genetic counseling prior to Assisted Reproductive Technology procedures in the
      era of cytogenomics.
AB  - The possibility of sequencing hundreds of genes simultaneously and performing
      molecular karyotyping thanks to the introduction of novel genetic tools has
      expanded the use of preconception screening for blastocyst recessive mutations
      and aneuploidies before embryo transfer, with the ultimate purpose of increasing
      the proportion of normal healthy newborns. Since medically-assisted reproduction
      procedures are increasingly required to be eugenic, and the aforementioned
      genetic tests cover only half of the potential genetic diseases occurring at
      birth, it seems reasonable to incorporate genetic counseling in the practice of
      assisted reproduction to avoid prosecution for malpractice.

PMID- 30106544
TI  - Nitrite-induced testicular toxicity in rats: therapeutic potential of walnut oil.
AB  - OBJECTIVE: To determine the impact of walnut oil on nitrite-induced testicular
      toxicity in Sprague-Dawley (SD) rats. Available evidence suggests that walnut oil
      contains high levels of important unsaturated fatty acids including alpha
      linolenic acid (ALA) and omega-3; nitrite is a reproductive toxicant that causes
      the loss of germ cells in the seminiferous tubules and generates oxidative stress
      in the testes, thus reducing sperm counts and affecting sperm morphology.
      METHODS: This study included 24 male and 24 female adult SD rats. The male rats
      randomly assigned to Group A (controls) were given normal saline 2 ml/kg. The
      rats in Groups B, C, and D were given 50mg/kg body weight (bwt) of walnut oil,
      0.08 mg/kg bwt of nitrite, and 0.08 mg/kg bwt of nitrite + 50 mg/kg of walnut oil
      respectively for 28 days via gastric gavage. Tested parameters included:
      testicular histology, sperm parameters, reproductive hormones, fertility,
      malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione, and
      catalase (CAT). RESULTS: A severe decrease in spermatogenic cell series,
      hypocellularity, tubular atrophy, decreased sperm quality, and increased MDA
      levels were observed in the rats given nitrite only when compared to controls.
      Rats given 50 mg/kg of walnut oil had significant growth of seminiferous
      epithelium compared to controls. The rats given walnut oil and nitrite had
      significant growth of seminiferous epithelium, improved sperm quality, and had
      decreased MDA levels. CONCLUSION: Walnut oil attenuated the deleterious effects
      of nitrite to the testes, reduced oxidative stress, and promoted spermatogenesis.

PMID- 30106542
TI  - The effects of male age on sperm DNA damage: an evaluation of 2,178 semen
      samples.
AB  - OBJECTIVE: This study aimed to evaluate the effects of male age on sperm DNA
      damage. METHODS: This cross-sectional study included semen samples collected from
      2,178 men seen at an infertility clinic. For DNA integrity analysis, the
      proportions of spermatozoa showing DNA fragmentation (TUNEL assay), abnormal
      chromatin packaging/underprotamination (chromomycin A3), abnormal mitochondrial
      membrane potential (MMP/MitoTracker Green), and apoptosis (annexin V) were
      recorded. For group comparisons, enrolled subjects were divided into three groups
      based on their ages: <=35 years; 36-44 years; and >=45 years. The associations
      between age and sperm parameters were assessed using Spearman's rank correlation
      coefficient. RESULTS: Although aging did not affect sperm apoptosis (p>.05),
      sperm DNA fragmentation and MMP deteriorated significantly with age (p<.05).
      Chromatin packaging/protamination improved significantly with age (p<.05).
      CONCLUSION: Sperm DNA fragmentation worsened with age and was apparently
      associated with mitochondrial damage. The age-related increase in sperm DNA
      damage suggests that delaying childbearing, not only in women but also in men,
      might jeopardize a couple's reproductive capacity. The increase seen in chromatin
      packaging might represent a protective feature for DNA. However, additional
      studies must be performed to confirm the results concerning chromatin
      packaging/protamination.

PMID- 30106554
TI  - Correction to "Correlation of device Performance and Fermi Level Shift in the
      Emitting Layer of Organic Light-Emitting Diodes with Amine-Based Electron
      Injection Layers".

PMID- 30106555
TI  - Gold Nanoparticle Plasmonic Superlattices as Surface-Enhanced Raman Spectroscopy
      Substrates.
AB  - Metal colloids are of great interest in the field of nanophotonics, mainly due to
      their morphology-dependent optical properties, but also because they are high
      quality building blocks for complex plasmonic architectures. Close-packed
      colloidal supercrystals not only serve for investigating the rich plasmonic
      resonances arising in strongly coupled arrangements but also enable tailoring the
      optical response, on both the nano- and the macroscale. Bridging these vastly
      different length scales at reasonable fabrication costs has remained
      fundamentally challenging, but is essential for applications in sensing,
      photovoltaics or optoelectronics, among other fields. We present here a scalable
      approach to engineer plasmonic supercrystal arrays, based on the template
      assisted assembly of gold nanospheres with topographically patterned
      polydimethylsiloxane molds. Regular square arrays of hexagonally packed
      supercrystals were achieved, reaching periodicities down to 400 nm and feature
      sizes around 200 nm, over areas up to 0.5 cm2. These two-dimensional
      supercrystals exhibit well-defined collective plasmon modes that can be tuned
      from the visible through the near-infrared by simple variation of the lattice
      parameter. We present electromagnetic modeling of the physical origin of the
      underlying hybrid modes and demonstrate the application of superlattice arrays as
      surface-enhanced Raman scattering (SERS) spectroscopy substrates which can be
      tailored for a specific probe laser. We therefore investigated the influence of
      the lattice parameter, local degree of order, and cluster architecture to
      identify the optimal configuration for highly efficient SERS of a nonresonant
      Raman probe with 785 nm excitation.

PMID- 30106556
TI  - Self-Healing Label Materials Based on Photo-Cross-Linkable Polymeric Films with
      Dynamic Surface Structures.
AB  - Spatially controlling the evolution of surface structures may provide an
      effective strategy for patterning surface roughness and facilitating the
      construction of various functional surfaces. In this study, we report a photo
      cross-linkable polymeric film with dynamic surface micro/nanostructures. The
      surface structures of the un-cross-linked regions can be eliminated under
      saturated humidity, which can be utilized to create patterned roughness on the
      film. One potential application of this patternable platform is as a "smart"
      label material for graphical symbols. Various graphical symbols can be programmed
      onto this film by partially erasing its surface roughness, enabling visibility
      due to the difference in light scattering between different areas of the film.
      When a thus-prepared label was blurred by mechanical scratches, it could be
      healed under saturated humidity, and its original readability could be fully
      restored. Furthermore, the patterned rough surface created using our approach can
      also be very useful in many other research fields, such as surface wettability
      and cell behavior manipulation.

PMID- 30106557
TI  - Controlling Supramolecular Chiral Nanostructures by Self-Assembly of a Biomimetic
      beta-Sheet-Rich Amyloidogenic Peptide.
AB  - Squid sucker ring teeth (SRT) have emerged as a promising protein-only,
      thermoplastic biopolymer with an increasing number of biomedical and engineering
      applications demonstrated in recent years. SRT is a supra-molecular network
      whereby a flexible, amorphous matrix is mechanically reinforced by nanoconfined
      beta-sheets. The building blocks for the SRT network are a family of suckerin
      proteins that share a common block copolymer architecture consisting of amorphous
      domains intervened by smaller, beta-sheet forming modules. Recent studies have
      identified the peptide A1H1 (peptide sequence AATAVSHTTHHA) as one of the most
      abundant beta-sheet forming domains within the suckerin protein family. However,
      we still have little understanding of the assembly mechanisms by which the A1H1
      peptide may assemble into its functional load-bearing domains. In this study, we
      conduct a detailed self-assembly study of A1H1 and show that the peptide
      undergoes beta-strands-driven elongation into amyloid-like fibrils with a rich
      polymorphism. The nanostructure of the fibrils was elucidated by small and wide
      angle X-ray scattering (SAXS and WAXS) and atomic force microscopy (AFM). The
      presence of His-rich and Ala-rich segments results in an amphiphilic behavior and
      drives its assembly into fibrillar supramolecular chiral aggregates with helical
      ribbon configuration in solution, with the His-rich region exposed to the solvent
      molecules. Upon increase in concentration, the fibrils undergo gel formation,
      while preserving the same mesoscopic features. This complex phase behavior
      suggests that the repeat peptide modules of suckerins may be manipulated beyond
      their native biological environment to produce a wider variety of self-assembled
      amyloid-like nanostructures.

PMID- 30106558
TI  - Nonfouling, Encoded Hydrogel Microparticles for Multiplex MicroRNA Profiling
      Directly from Formalin-Fixed, Paraffin-Embedded Tissue.
AB  - MicroRNAs (miRNA) are short, noncoding RNAs that have been implicated in many
      diseases, including cancers. Because miRNAs are dysregulated in disease, miRNAs
      show promise as highly stable biomarkers. Formalin-fixed, paraffin-embedded
      (FFPE) tissue is a valuable sample type to assay for biomolecules because it is a
      convenient storage method and is often used by pathologists for histological
      staining. However, extracting biomolecules from FFPE tissue is challenging
      because of the presence of cellular and extracellular proteins, formaldehyde
      cross-links, and paraffin. Moreover, most protocols to measure miRNA in FFPE
      tissue are time-consuming and laborious. Here, we report a simple protocol to
      directly measure miRNA from formalin-fixed cells, FFPE tissue sections after
      paraffin is removed, and FFPE tissue sections using encoded hydrogel
      microparticles fabricated using stop flow lithography. Measurements by these
      particles show agreement between formalin-fixed cells and fresh cells, and
      measurement of FFPE tissue with paraffin is 10% less than FFPE tissue when
      paraffin is removed before the assay. When normal and tumor FFPE tissue are
      compared using this microparticle assay, we observe differential miRNA signal for
      oncogenic miRNAs and tumor suppressing miRNAs. This approach reduces assay times,
      reduces the use of hazardous chemicals to remove paraffin, and provides a
      sensitive, quantitative, and multiplexed measurement of miRNA in FFPE tissue.

PMID- 30106559
TI  - Supramolecular Organic Photocatalyst Containing a Cubanelike Water Cluster and
      Donor-Acceptor Stacks: Hydrogen Evolution and Dye Degradation under Visible
      Light.
AB  - Supramolecular organic photocatalysts are scarcely explored for the generation of
      sustainable energy as well as for environmental remediation purposes. An organic
      photocatalyst, containing a cubanelike water cluster and donor-acceptor stacks,
      was efficiently developed through a supramolecular approach. The material
      exhibited remarkable photocatalytic hydrogen generation, in the absence of any
      cocatalyst, with excellent stability and recyclability. The photoactivity was
      further assessed through time-resolved photoluminescence and electrochemical
      impedance spectroscopy. The material also exhibited highly efficient sunlight
      driven photocatalytic activity through the degradation of harmful organic dye
      methylene blue.

PMID- 30106560
TI  - Roadblocks in Cation Diffusion Pathways: Implications of Phase Boundaries for Li
      Ion Diffusivity in an Intercalation Cathode Material.
AB  - Increasing intercalation of Li-ions brings about distortive structural
      transformations in several canonical intercalation hosts. Such phase
      transformations require the energy dissipative creation and motion of
      dislocations at the interface between the parent lattice and the nucleated Li
      rich phase. Phase inhomogeneities within particles and across electrodes give
      rise to pronounced stress gradients, which can result in capacity fading. How
      such transformations alter Li-ion diffusivities remains much less explored. In
      this article, we use layered V2O5 as an intercalation host and examine the
      structural origins of the evolution of Li-ion diffusivities with phase
      progression upon electrochemical lithiation. Galvanostatic intermittent titration
      measurements show a greater than 4 orders of magnitude alteration of Li-ion
      diffusivity in V2O5 as a function of the extent of lithiation. Pronounced dips in
      Li-ion diffusivities are correlated with the presence of phase mixtures as
      determined by Raman spectroscopy and X-ray diffraction, whereas monophasic
      regimes correspond to the highest Li-ion diffusivity values measured within this
      range. First-principles density functional theory calculations confirm that the
      variations in Li-ion diffusivity do not stem from intrinsic differences in
      diffusion pathways across the different lithiated V2O5 phases, which despite
      differences in the local coordination environments of Li-ions show comparable
      migration barriers. Scanning transmission X-ray microscopy measurements indicate
      the stabilization of distinct domains reflecting the phase coexistence of
      multiple lithiated phases within individual actively intercalating particles. The
      results thus provide fundamental insight into the considerable ion transport
      penalties incurred as a result of phase boundaries formed within actively
      intercalating particles. The combination of electrochemical studies with ensemble
      structural characterization and single-particle X-ray imaging of phase boundaries
      demonstrates the profound impact of interfacial phenomena on macroscopic
      electrode properties.

PMID- 30106561
TI  - Janus Nanoparticle Structural Motif Control via Asymmetric Cation Exchange in
      Edge-Protected Cu1.81S@Ir xS y Hexagonal Nanoplates.
AB  - Post-synthetic transformation of nanoparticles has received great attention,
      because this approach can provide an unusual route to elaborately composition
      controlled nanostructures while maintaining the overall structure of the
      template. In principle, anisotropic heteronanoparticles of semiconductor
      materials can be synthesized via localized, that is, single site, cation exchange
      in symmetric nanoparticles. However, the differentiation of multiple identical
      cation exchange sites in symmetric nanoparticles can be difficult to achieve,
      especially for semiconductor systems with very fast cation exchange kinetics. We
      posited that single-site cation exchange in semiconductor nanoparticles might be
      realized by imposing a significant kinetic hurdle to the cation exchange
      reaction. The different atomic arrangements of the core and crown in core-crown
      structures might further differentiate the surface energies of originally
      identical cation exchange sites, leading to different reactivities of these
      sites. The first cation exchange site would be highly reactive due to the
      presence of a formed interface, thereby continuing to act as a site for cation
      exchange propagation. Herein, we present the proof-of-concept synthesis of Janus
      nanoparticles by using edge-protected Cu1.81S@Ir xS y hexagonal nanoplates. The
      Janus nanoparticles comprising {Au2S-Cu1.81S}@Ir xS y or {PdS-Cu1.81S}@Ir xS y
      exhibited dissimilar structural motifs due to the disparate cation exchange
      directions. This synthetic methodology exploiting cation exchange of surface
      passivated semiconductor nanoparticles could fabricate the numerous symmetry
      controlled Janus heterostructures.

PMID- 30106562
TI  - High-Throughput Chip Assay for Investigating Escherichia coli Interaction with
      the Blood-Brain Barrier Using Microbial and Human Proteome Microarrays (Dual
      Microarray Technology).
AB  - Bacterial meningitis in neonates and infants is an acute lethal disease and
      occurs in response to microbial exploitation of the blood-brain barrier (BBB),
      resulting in the intracranial inflammation. Several pathogens, such as
      Escherichia coli ( E. coli), can cause this devastating disease; however, the
      underlying molecular mechanisms by which these pathogens exploit the BBB remain
      incompletely understood. To identify important players on both the pathogen and
      host sides that govern the E. coli-BBB cell interactions, we took advantage of
      the E. coli and human proteome microarrays (i.e., HuProt) as an unbiased,
      proteome-wide tool for identification of important players on both sides. Using
      the E. coli proteome microarrays, we developed a unique high throughput chip
      based cell probing assay to probe with fluorescent live human brain microvascular
      endothelial cells (HBMEC, which constitute the BBB). We identified several
      transmembrane proteins, which effectively bound to live HBMEC. We focused on YojI
      protein for further study. By probing the HuProt arrays with YojI, interferon
      alpha receptor (IFNAR2) was identified as one of its binding proteins. The
      importance of YojI and IFNAR2 involved in E. coli-HBMEC interactions was
      characterized using the YojI knockout bacteria and IFNAR2-knock down HBMEC and
      further confirmed by E. coli binding assay in HBMEC. This study represents a new
      paradigm (dual-microarray technology) that enables rapid, unbiased discovery of
      both pathogen and host players that are involved in pathogen-host interactions
      for human infectious diseases in a high throughput manner.

PMID- 30106563
TI  - Graphene Quantum Dots Based Systems As HIV Inhibitors.
AB  - Graphene quantum dots (GQD) are the next generation of nanomaterials with great
      potential in drug delivery and target-specific HIV inhibition. In this study we
      investigated the antiviral activity of graphene based nanomaterials by using
      water-soluble GQD synthesized from multiwalled carbon nanotubes (MWCNT) through
      prolonged acidic oxidation and exfoliation and compared their anti-HIV activity
      with that exerted by reverse transcriptase inhibitors (RTI) conjugated with the
      same nanomaterial. The antiretroviral agents chosen in this study, CHI499 and
      CDF119, belong to the class of non-nucleoside reverse transcriptase inhibitors
      (NNRTI). From this study emerged the RTI-conjugated compound GQD-CHI499 as a good
      potential candidate for HIV treatment, showing an IC50 of 0.09 MUg/mL and an EC50
      value in cell of 0.066 MUg/mL. The target of action in the replicative cycle of
      HIV of the drug conjugated samples GQD-CHI499 and GQD-CDF119 was also
      investigated by a time of addition (TOA) method, showing for both conjugated
      samples a mechanism of action similar to that exerted by NNRTI drugs.

PMID- 30106564
TI  - Estimating Interprotein Pairwise Interaction Energies in Cell Lysates from a
      Single Native Mass Spectrum.
AB  - A powerful method to determine the energetic coupling between amino acids is
      double mutant cycle analysis. In this method, two residues are mutated separately
      and in combination and the energetic effects of the mutations are determined. A
      deviation of the effect of the double mutation from the sum of effects of the
      single mutations indicates that the two residues are interacting directly or
      indirectly. Here, we show that double mutant cycle analysis by native mass
      spectrometry can be carried out for interactions in crude Escherichia coli cell
      extracts, thereby obviating the need for protein purification and generating
      binding isotherms. Our results indicate that intermolecular hydrogen bond
      strengths are not affected by the more crowded conditions in cell lysates.

PMID- 30106566
TI  - Dual Electrolytic Eluent Generation for Oligosaccharides Analysis Using High
      Performance Anion-Exchange Chromatography.
AB  - The research on oligosaccharides is growing and gaining in importance at a rapid
      pace. The efforts to understand their bioactivity and to develop new products
      based on oligosaccharides in biotherapeutics and food industry require effective
      and reliable tools for analysis of oligosaccharides. Here we present a dual
      electrolytic eluent generation platform for the analysis of oligosaccharides by
      high-performance anion-exchange liquid chromatography (HPAE) in both analytical
      and capillary column formats. The system consists of one eluent generator
      producing methanesulfonic acid (MSA) connected in series with a second eluent
      generator producing potassium hydroxide (KOH). Through manipulating the
      concentration output of both eluent generators, chromatographic performance
      comparable to that obtained using the conventional sodium acetate/sodium
      hydroxide (NaOAc/NaOH) eluents is achieved using the electrolytically generated
      potassium methanesulfonate/potassium hydroxide (KMSA/KOH) eluent. This platform
      utilizes deionized water as the only carrier stream through a single isocratic
      pump, overcomes the various drawbacks associated with manually prepared
      NaOAc/NaOH eluents, and offers an easy to use, simplified operation solution for
      oligosaccharides profiling with increased precision and accuracy.

PMID- 30106565
TI  - A Noncanonical Metal Center Drives the Activity of the Sediminispirochaeta
      smaragdinae Metallo-beta-lactamase SPS-1.
AB  - In an effort to evaluate whether a recently reported putative metallo-beta
      lactamase (MbetaL) contains a novel MbetaL active site, SPS-1 from
      Sediminispirochaeta smaragdinae was overexpressed, purified, and characterized
      using spectroscopic and crystallographic studies. Metal analyses demonstrate that
      recombinant SPS-1 binds nearly 2 equiv of Zn(II), and steady-state kinetic
      studies show that the enzyme hydrolyzes carbapenems and certain cephalosporins
      but not beta-lactam substrates with bulky substituents at the 6/7 position.
      Spectroscopic studies of Co(II)-substituted SPS-1 suggest a novel metal center in
      SPS-1, with a reduced level of spin coupling between the metal ions and a novel
      Zn1 metal binding site. This site was confirmed with a crystal structure of the
      enzyme. The structure shows a Zn2 site that is similar to that in NDM-1 and other
      subclass B1 MbetaLs; however, the Zn1 metal ion is coordinated by two histidine
      residues and a water molecule, which is held in position by a hydrogen bond
      network. The Zn1 metal is displaced nearly 1 A from the position reported in
      other MbetaLs. The structure also shows extended helices above the active site,
      which create a binding pocket that precludes the binding of substrates with
      large, bulky substituents at the 6/7 position of beta-lactam antibiotics. This
      study reveals a novel metal binding site in MbetaLs and suggests that the
      targeting of metal binding sites in MbetaLs with inhibitors is now more
      challenging with the identification of this new MbetaL.

PMID- 30106567
TI  - High-Throughput Breath Volatile Organic Compound Analysis Using Thermal
      Desorption Proton Transfer Reaction Time-of-Flight Mass Spectrometry.
AB  - Breath analysis is highly acceptable to patients and health care professionals,
      but its implementation in clinical practice remains challenging. Clinical trials
      and routine practice require a robust system for collection, storage, and
      processing of large numbers of samples. This work describes a platform based upon
      the hyphenation of thermal desorption (TD) with proton transfer reaction time-of
      flight mass spectrometry (PTR-ToF-MS), coupled by means of an original
      modification of the TD interface. The performance of TD-PTR-ToF-MS was tested
      against seven oxygenated volatile organic compounds (VOCs), belonging to three
      chemical classes (i.e., fatty acids, aldehydes, and phenols), previously
      identified as possible biomarkers of colorectal and esophago-gastric
      adenocarcinoma. Limits of detection and quantification were on the order of 0.2
      0.9 and 0.3-1.5 parts per billion by volume (ppbV), respectively. Analytical
      recoveries from TD tubes were 80% or higher, linear response was in the low- to
      mid-ppbV range ( R2 = 0.98-0.99), and coefficients of variation were within 20%
      of mean values. The usability of the platform was evaluated in the analysis of a
      set of breath samples of clinical origin, allowing for a throughput of nearly 100
      TD tubes for 24 h of continuous operation. All of these characteristics enhance
      the implementation of TD-PTR-ToF-MS for large-scale clinical studies.

PMID- 30106568
TI  - Intracation and Interanion-Cation Charge-Transfer Properties of
      Tetrathiafulvalene-Bismuth-Halide Hybrids.
AB  - Tetrathiafulvalene (TTF) derivatives as promising hole transport materials in
      assembling hybrid halide perovskite solar cells have attracted great attention;
      however, electron transfer or charge-transfer (CT) between TTF and metal halides
      has been studied with less detail at the molecular level. Using molecular models,
      we herein report four new TTF-bismuth-halides assembled by methylated or
      protonated bis(4'-pyridyl)-tetrathiafulvalene cations, (MePy)2TTF or (HPy)2TTF,
      and bismuth-halide anions. Single crystal analysis showed that the cations are
      stacked to form a TTF column, and the bismuth-halide anions are inlaid between
      the TTF columns with anion-cation interactions. In these compounds, the main
      contribution to CT is the intracation CT, namely intramolecular CT (IMCT) from
      TTF moiety to pyridinium group. However, the anion to cation CT (ACCT) has a
      significant effect on the IMCT and physical properties. The different anion
      cation interaction modes result in different synergistic effects of IMCT and
      ACCT, which modified the band gaps and photocurrent properties of the hybrids.
      The research gives a clear image of structure-property relationship and provides
      a perspective on the design of new perovskite materials at the molecular level.

PMID- 30106569
TI  - Alkaline-Earth Rhodium Hydroxides: Synthesis, Structures, and Thermal
      Decomposition to Complex Oxides.
AB  - The rhodium(III) hydrogarnets Ca3Rh2(OH)12 and Sr3Rh2(OH)12 crystallize as
      polycrystalline powders under hydrothermal conditions at 200  degrees C from
      RhCl3.3H2O and either Ca(OH)2 or Sr(OH)2 in either 12 M NaOH or KOH. Rietveld
      refinements against synchrotron powder X-ray diffraction (XRD) data allow the
      first crystal structures of the two materials to be determined. If BaO2 is used
      as a reagent and the concentration of hydroxide increased to hydroflux conditions
      (excess NaOH), then single crystals of a new complex rhodium hydroxide,
      BaNaRh(OH)6, are formed in a phase-pure sample, with sodium included from the
      flux. Structure solution from single-crystal XRD data reveals isolated octahedral
      Rh centers that share hydroxides with 10-coordinate Ba and two independent 8
      coordinate Na sites. 23Na magic-angle spinning NMR confirms the presence of the
      two crystallographically distinct Na sites and also verifies the diamagnetic
      nature of the sample, expected for Rh(III). The thermal behavior of the
      hydroxides on heating in air was investigated using X-ray thermodiffractometry,
      showing different decomposition pathways for each material. Ca3Rh2(OH)12 yields
      CaRh2O4 and CaO above 650  degrees C, from which phase-pure CaRh2O4 is isolated
      by washing with dilute nitric acid, a material previously only reported by high
      pressure or high-temperature synthesis. Sr3Rh2(OH)12 decomposes to give a less
      crystalline material with a powder XRD pattern that is matched to the 2H-layered
      hexagonal perovskite Sr6Rh5O15, which contains mixed-valent Rh3+/4+, confirmed by
      Rh K-edge XANES spectroscopy. On heating BaNaRh(OH)6, a complex set of
      decomposition events takes place via transient phases.

PMID- 30106570
TI  - Sulfate Donor Based Dinuclear Heteroleptic Triple-Stranded Helicates from Sulfite
      and Ditopic Nitrogen Donor Ligands and Their Transformation to Dinuclear
      Homoleptic Double-Stranded Mesocates.
AB  - Sulfate donor based supramolecular coordination complexes [{ fac-Re(CO)3}(MU
      SO4)(L n)2{ fac-Re(CO)3}] (1-3) were obtained using ditopic N donors (L n; n = 1
      3), NaHSO3, and Re2(CO)10 in a one-pot, multicomponent, coordination-driven self
      assembly approach, in which SO32- becomes oxidized to SO42- during the reaction
      and acts as a building framework. Complexes 1-3 were characterized using IR, ESI
      TOF-MS, and 1H NMR spectroscopy. The structures of complexes 1-3 were confirmed
      using single-crystal X-ray diffraction analysis. The transformation of the
      dinuclear heteroleptic triple-stranded helicate to the dinuclear homoleptic
      double-stranded mesocate [{Re(CO)3Cl}2(L n)2] (L n = L1, L2, L3; 4a-6a) was
      achieved by the addition of BaCl2. The direct treatment of Re(CO)5X (X = Cl, Br)
      with L1/L2/L3 yielded the dinuclear homoleptic double-stranded helicates
      [{Re(CO)3X}2 (L n)2] (4b-6b and 7-9).

PMID- 30106571
TI  - NO Releasing and Anticancer Properties of Octahedral Ruthenium-Nitrosyl Complexes
      with Equatorial 1 H-Indazole Ligands.
AB  - With the aim of enhancing the biological activity of ruthenium-nitrosyl
      complexes, new compounds with four equatorially bound indazole ligands, namely,
      trans-[RuCl(Hind)4(NO)]Cl2.H2O ([3]Cl2.H2O) and trans-[RuOH(Hind)4(NO)]Cl2.H2O
      ([4]Cl2.H2O), have been prepared from trans-[Ru(NO2)2(Hind)4] ([2]). When the pH
      dependent solution behavior of [3]Cl2.H2O and [4]Cl2.H2O was studied, two new
      complexes with two deprotonated indazole ligands were isolated, namely
      [RuCl(ind)2(Hind)2(NO)] ([5]) and [RuOH(ind)2(Hind)2(NO)] ([6]). All prepared
      compounds were comprehensively characterized by spectroscopic (IR, UV-vis, 1H
      NMR) techniques. Compound [2], as well as [3]Cl2.2(CH3)2CO, [4]Cl2.2(CH3)2CO, and
      [5].0.8CH2Cl2, the latter three obtained by recrystallization of the first
      isolated compounds (hydrates or anhydrous species) from acetone and
      dichloromethane, respectively, were studied by X-ray diffraction methods. The
      photoinduced release of NO in [3]Cl2 and [4]Cl2 was investigated by cyclic
      voltammetry and resulting paramagnetic NO species were detected by EPR
      spectroscopy. The quantum yields of NO release were calculated and found to be
      low (3-6%), which could be explained by NO dissociation and recombination
      dynamics, assessed by femtosecond pump-probe spectroscopy. The geometry and
      electronic parameters of Ru species formed upon NO release were identified by DFT
      calculations. The complexes [3]Cl2 and [4]Cl2 showed considerable
      antiproliferative activity in human cancer cell lines with IC50 values in low
      micromolar or submicromolar concentration range and are suitable for further
      development as potential anticancer drugs. p53-dependence of Ru-NO complexes
      [3]Cl2 and [4]Cl2 was studied and p53-independent mode of action was confirmed.
      The effects of NO release on the cytotoxicity of the complexes with or without
      light irradiation were investigated using NO scavenger carboxy-PTIO.

PMID- 30106572
TI  - Off to the Races: Comparison of Excited State Dynamics in Vitamin B12 Derivatives
      Hydroxocobalamin and Aquocobalamin.
AB  - Ultrafast time-resolved spectroscopy was used to study the photochemistry of
      hydroxocobalamin (HOCbl) and aquocobalamin (H2OCbl+) in solution. Spectroscopic
      measurements and TD-DFT simulations provide a consistent picture of the
      spectroscopy and photochemistry. Excitation of H2OCbl+ results in formation of an
      excited state followed by rapid internal conversion to the ground state (0.35 +/-
      0.15 ps) through an S1/S0 seam at a slightly elongated Co-O bond length and a
      significantly elongated Co-NIm bond length. In contrast, the initial elongation
      of the axial bonds in HOCbl is followed by contraction to an excited state
      minimum with bonds slightly shorter than those in the ground state. Internal
      conversion to the ground state follows on a picosecond time scale (5.3 +/- 0.4
      ps). For both compounds, photodissociation forming cob(II)alamin and hydroxyl
      radicals (~1.5% yield) requires excitation to highly excited states. Dissociation
      is mediated by competition between internal conversion to the S1 surface and
      prompt bond cleavage.

PMID- 30106573
TI  - Construction of 3,4-Dihydroisoquinolinones and Indanones via DTBP-Promoted
      Oxidative Coupling of N-Allylbenzamides with Aromatic Aldehydes.
AB  - A metal-free oxidative tandem coupling of N-allylbenzamide with aryl aldehydes
      was realized. This method allowed the 1,2-difunctionalization of the C?C double
      bond in N-allylbenzamides through simultaneous formation of two C(sp2)-C(sp3)
      bonds. In the presence of DTBP, 4-substituted 3,4-dihydroisoquinolin-1(2 H)-ones
      were obtained in satisfactory isolated yields. 3-Substituted indanones could also
      be formed by varying the structures of the starting materials.

PMID- 30106574
TI  - QM/MM Study of Tungsten-Dependent Benzoyl-Coenzyme A Reductase: Rationalization
      of Regioselectivity and Predication of W vs Mo Selectivity.
AB  - The class II benzoyl-coenzyme A reductase (BCR) is a tungsten-dependent enzyme
      that catalyzes the Birch reduction of benzoyl-CoA to a cyclic diene. The reaction
      mechanism and regioselectivity of benzoyl-CoA were explored through QM/MM
      calculations using two different QM regions (124 atoms and 223 atoms) on the
      solvated enzyme. The reduction reaction involves two major chemical steps that
      both proceed in the triplet state or in the broken-symmetry singlet state. First,
      the tungsten-bound water molecule delivers a proton to the C4 of the benzoyl-CoA
      substrate, coupled with an electron transfer from the WIV center to the
      substrate. This leads to the formation of a WV-radical intermediate, with a
      barrier of 23.2 kcal/mol in the broken-symmetry singlet state at the B3LYP
      D3/def2-TZVPP:Charmm level. Subsequently, the protonated His260 residue delivers
      a second proton to C3 of the benzoyl-CoA substrate, concomitantly with the shift
      of the second electron from the pyranopterin cofactor rather than the WV ion to
      the substrate, which has a barrier of 19.1 kcal/mol at the B3LYP-D3/def2
      TZVPP:Charmm level and produces the cyclohexa-1,5-diene-1-carboxyl-CoA product.
      The reduction of the aromatic ring at other positions has also been considered;
      however, the barriers are much higher, which shows that the cyclohexa-1,5-diene-1
      carboxyl-CoA product is exclusively formed during the benzoyl-CoA reduction.
      Moreover, molybdenum, tungsten's lighter congener, has also been considered to
      replace the tungsten ion in the benzoyl-CoA reductase. The molybdenum substituted
      enzyme (Mo-BCR) was found to have a quite higher barrier for the reduction
      reaction, but a feasible barrier for the reverse oxidation reaction.

PMID- 30106575
TI  - Electronic Structure of Two Catalytic States of the [FeFe] Hydrogenase H-Cluster
      As Probed by Pulse Electron Paramagnetic Resonance Spectroscopy.
AB  - The active site of the [FeFe] hydrogenase (HydA1), the H-cluster, is a 6-Fe
      cofactor that contains CO and CN- ligands. It undergoes several different
      oxidation and protonation state changes in its catalytic cycle to metabolize H2.
      Among them, the well-known Hox state and the recently identified Hhyd state are
      thought to be directly involved in H2 activation and evolution, and they are both
      EPR active with net spin S = 1/2. Herein, we report the pulse electronic
      paramagnetic spectroscopic investigation of these two catalytic states in
      Chlamydomonas reinhardtii HydA1 ( CrHydA1). Using an in vitro biosynthetic
      maturation approach, we site-specifically installed 13C into the CO or CN-
      ligands and 57Fe into the [2Fe]H subcluster of the H-cluster in order to measure
      the hyperfine couplings to these magnetic nuclei. For Hox, we measured 13C
      hyperfine couplings (13CO aiso of 25.5, 5.8, and 4.5 MHz) corresponding to all
      three CO ligands in the H-cluster. We also observed two 57Fe hyperfine couplings
      (57Fe aiso of ~17 and 5.7 MHz) arising from the two Fe atoms in the [2Fe]H
      subcluster. For Hhyd, we only observed two distinct 13CO hyperfine interactions
      (13CO aiso of 0.16 and 0.08 MHz) and only one for 13CN- (13CN aiso of 0.16 MHz);
      the couplings to the 13CO/13CN- on the distal Fe of [2Fe]H may be too small to
      detect. We also observed a very small (<0.3 MHz) 57Fe HFI from the labeled [2Fe]H
      subcluster and four 57Fe HFI from the labeled [4Fe-4S]H subcluster (57Fe aiso of
      7.2, 16.6, 28.2, and 35.3 MHz). These hyperfine coupling constants are consistent
      with the previously proposed electronic structure of the H-cluster at both Hox
      and Hhyd states and provide a basis for more detailed analysis.

PMID- 30106576
TI  - Application of Naphthylindole-Derived Phosphines as Organocatalysts in [4 + 1]
      Cyclizations of o-Quinone Methides with Morita-Baylis-Hillman Carbonates.
AB  - An organocatalytic [4 + 1] cyclization of o-QMs with MBH carbonates has been
      established using naphthylindole-derived phosphine (NIP) as an organocatalyst. By
      using this approach, a series of 2,3-dihydrobenzofuran derivatives have been
      synthesized in high yields and excellent diastereoselectivities (up to 99% yield,
      >95:5 dr). This reaction not only has established the first [4 + 1] cyclization
      of o-QMs with MBH carbonates but also represents the first application of
      naphthylindole-derived phosphines as organocatalysts in catalytic reactions. In
      addition, this reaction has also provided a useful method for constructing 2,3
      dihydrobenzofuran scaffolds.

PMID- 30106577
TI  - Low-Frequency Phonon Driven Negative Thermal Expansion in Cubic GaFe(CN)6
      Prussian Blue Analogues.
AB  - The understanding of the negative thermal expansion (NTE) mechanism is vital not
      only for the development of new NTE compounds but also for effectively
      controlling thermal expansion. Here, we report an interesting isotropic NTE
      property in cubic GaFe(CN)6 Prussian blue analogues (alpha l = -3.95 * 10-6 K-1,
      100-475 K), which is a new example to understand the complex NTE mechanism. A
      combined study of synchrotron X-ray diffraction, X-ray total scattering, X-ray
      absorption fine structure, neutron powder diffraction, and density functional
      theory calculations shows that the NTE of GaFe(CN)6 originates from the low
      frequency phonons (< ~100 cm-1), which are directly related to the transverse
      vibrations of the atomic -Ga-N=C-Fe- chains. Both the Ga-N and Fe-C chemical
      bonds are much softer to bend than to stretch. The direct evidence that
      transverse vibrational contribution to the NTE of GaFe(CN)6 is dominated by N,
      instead of C atoms, is illustrated. It is interesting to find that the polyhedra
      of GaFe(CN)6 are not rigid, which is a starting assumption in some models
      describing the NTE properties of other systems. The NTE mechanism can be vividly
      described by the "guitar-string" effect, which would be the common feature for
      the NTE property of many open-framework functional materials, such as Prussian
      blue analogues, oxides, cyanides, metal-organic frameworks, and zeolites.

PMID- 30106578
TI  - Allosteric Modulation of Class A GPCRs: Targets, Agents, and Emerging Concepts.
AB  - G-protein-coupled receptors (GPCRs) have been tractable drug targets for decades
      with over one-third of currently marketed drugs targeting GPCRs. Of these, the
      class A GPCR superfamily is highly represented, and continued drug discovery for
      this family of receptors may provide novel therapeutics for a vast range of
      diseases. GPCR allosteric modulation is an innovative targeting approach that
      broadens the available small molecule toolbox and is proving to be a viable drug
      discovery strategy, as evidenced by recent FDA approvals and clinical trials.
      Numerous class A GPCR allosteric modulators have been discovered recently, and
      emerging trends such as the availability of GPCR crystal structures, diverse
      functional assays, and structure-based computational approaches are improving
      optimization and development. This Perspective provides an update on
      allosterically targeted class A GPCRs and their disease indications and the
      medicinal chemistry approaches toward novel allosteric modulators and highlights
      emerging trends and opportunities in the field.

PMID- 30106579
TI  - Optimizing Protein-Polymer Interactions in a Poly(ethylene glycol) Coarse-Grained
      Model.
AB  - Increasing demand for hybrid materials that merge the synthetic and biological
      areas in drug industries requires in-depth knowledge of the individual components
      and their contributions to these complexes. Coarse-grained (CG) models developed
      for proteins and polymers exist, yet there is a lack of understanding of the
      cross interactions when these two groups of materials integrate to build a
      complex. In this work, we characterized the nonbonded interactions between
      poly(ethylene glycol) (PEG) and amino acids in a Martini CG model utilizing state
      of-the-art quantum mechanics calculations of interaction energies. The parameter
      set proposed, was validated by assessing the polymer density in the vicinity of
      individual amino acids obtained from available all-atomistic molecular dynamic
      simulations of plasma proteins. Our results revealed the necessity of protein
      polymer interaction parameterization at the CG level to avoid overestimation of
      polymer association when employing other PEG models within the Martini framework.

PMID- 30106580
TI  - Multiferroism in Iron-Based Oxyfluoride Perovskites.
AB  - Multiferroic materials with simultaneous magnetic and ferroelectric ordering that
      persist above room temperature are rare. Using first-principles density
      functional theory calculations, we demonstrate fluorination of oxygen-deficient
      AA'Fe2O5 perovskites, where A and A' are cations with +3 and +2 oxidation states,
      respectively, and have a layered ordering, as an effective strategy to obtain
      room-temperature multiferroics. We show that by controlling the size of the A and
      A' cations, it is possible to stabilize a noncentrosymmetric phase arising due to
      the hybrid improper ferroelectricity mechanism, with polarization as high as 13
      MUC/cm2. The fluorination also stabilizes Fe in +3 oxidation state, which results
      in superexchange interactions that are strong enough to sustain magnetic order
      well above room temperature. We also show the presence of a magnetoelectric
      coupling wherein the switching mode that reverses the direction of the
      spontaneous polarization also affects the strength of the magnetic interactions.
      The results show that low-temperature fluorination of anion-deficient perovskites
      with layered cation ordering can be an effective approach to design new
      multiferroics.

PMID- 30106581
TI  - Tuning Regioselectivity of Wacker Oxidation in One Catalytic System: Small Change
      Makes Big Step.
AB  - A regioselectivity switchable aerobic Wacker-Tsuji oxidation has been developed
      using catalytic tert-butyl nitrite as a simple organic redox cocatalyst. By
      solely switching the solvent, either substituted aldehydes or ketones could be
      prepared under mild aerobic conditions in good yields, respectively. A
      mechanistic explanation for the selectivity control is proposed.

PMID- 30106583
TI  - Diffusivity of Mono- and Divalent Salts and Water in Polyelectrolyte Desalination
      Membranes.
AB  - The dynamics of ions and solvent molecules in polyelectrolyte desalination
      membranes is key to water purification technologies in which selective transport
      of the different components is desired. Recent experimental and our computational
      results have shown that nontrivial mechanisms underlie the transport properties
      of salt ions and water in charged polymer membranes. Explicitly, in polymer
      electrolytes, we found a reversal in the salt concentration dependence of the
      mobilities of Na+, Cl- salt ions and water molecules when compared with aqueous
      solutions. Motivated by such results, in this study, we have used atomistic
      molecular dynamics simulations to probe whether the mechanisms deduced in our
      earlier work apply to other salt systems and to mixtures of salts. Specifically,
      we report results for the ion diffusivities in aqueous KCl, MgCl2, and a 1:1
      mixture of NaCl and MgCl2 salt solutions at different concentrations (ranging
      from 0.06 to 1 M) and investigate, at the molecular level, the mechanisms
      underlying the behaviors of salt and water transport properties. Our results show
      that diffusion of salt ions and water in charged polymer membranes are in general
      influenced by their association with polymer charge groups and ion pairing
      effects. Divalent ions are more strongly coupled with the polymeric ionic groups
      than monovalent salt ions and exhibit diffusivity trends that are distinct
      relative to monovalent salts. Further, we demonstrate that the mobilities of
      water molecules are influenced by coordination of water with polymer charge
      groups and their ion pairing tendencies and also exhibit distinct trends in
      monovalent and divalent salt solutions.

PMID- 30106582
TI  - Correction to "A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase
      Separation".

PMID- 30106584
TI  - Conformational Properties of a Peptidic Catalyst: Insights from NMR Spectroscopic
      Studies.
AB  - Peptides have become valuable as catalysts for a variety of different reactions,
      but little is known about the conformational properties of peptidic catalysts. We
      investigated the conformation of the peptide H-dPro-Pro-Glu-NH2, a highly
      reactive and stereoselective catalyst for conjugate addition reactions, and the
      corresponding enamine intermediate in solution by NMR spectroscopy and
      computational methods. The combination of nuclear Overhauser effects (NOEs),
      residual dipolar couplings (RDCs), J-couplings, and temperature coefficients
      revealed that the tripeptide adopts a single predominant conformation in its
      ground state. The structure is a type I beta-turn, which gains stabilization from
      three hydrogen bonds that are cooperatively formed between all functional groups
      (secondary amine, carboxylic acid, amides) within the tripeptide. In contrast,
      the conformation of the enamine intermediate is significantly more flexible. The
      conformational ensemble of the enamine is still dominated by the beta-turn, but
      the backbone and the side chain of the glutamic acid residue are more dynamic.
      The key to the switch between rigidity and flexibility of the peptidic catalyst
      is the CO2H group in the side chain of the glutamic acid residue, which acts as a
      lid that can open and close. As a result, the peptidic catalyst is able to adapt
      to the structural requirements of the intermediates and transition states of the
      catalytic cycle. These insights might explain the robustness and high reactivity
      of the peptidic catalyst, which exceeds that of other secondary amine-based
      organocatalysts. The data suggest that a balance between rigidity and
      flexibility, which is reminiscent of the dynamic nature of enzymes, is beneficial
      for peptidic catalysts and other synthetic catalysts.

PMID- 30106585
TI  - Efficient 15N-13C Polarization Transfer by Third-Spin-Assisted Pulsed Cross
      Polarization Magic-Angle-Spinning NMR for Protein Structure Determination.
AB  - We introduce a pulsed third-spin-assisted recoupling experiment that produces
      high-intensity long-range 15N-13C cross peaks using low radiofrequency (rf)
      energy. This Proton-Enhanced Rotor-echo Short-Pulse IRradiATION Cross
      Polarization (PERSPIRATIONCP) pulse sequence operates with the same principle as
      the Proton-Assisted Insensitive-Nuclei Cross-Polarization (PAINCP) experiment but
      uses only a fraction of the rf energy by replacing continuous-wave 13C and 15N
      irradiation with rotor-echo 90 degrees  pulses. Using formyl-Met-Leu-Phe (f-MLF)
      and beta1 immunoglobulin binding domain of protein G (GB1) as model proteins, we
      demonstrate experimentally how PERSPIRATIONCP polarization transfer depends on
      the CP contact time, rf power, pulse flip angle, and 13C carrier frequency and
      compare the PERSPIRATIONCP performance with the performances of PAINCP,
      RESPIRATIONCP, and SPECIFICCP for measuring 15N-13C cross peaks. PERSPIRATIONCP
      achieves long-range 15N-13C transfer and yields higher cross peak-intensities
      than that of the other techniques. Numerical simulations reproduce the
      experimental trends and moreover indicate that PERSPIRATIONCP relies on 15N-1H
      and 13C-1H dipolar couplings rather than 15N-13C dipolar coupling for
      polarization transfer. Therefore, PERSPIRATIONCP is an rf-efficient and higher
      sensitivity alternative to PAINCP for measuring long-range 15N-13C correlations,
      which are essential for protein resonance assignment and structure determination.
      Using cross peaks from two PERSPIRATIONCP 15N-13C correlation spectra as the sole
      distance restraints, supplemented with (phi, psi) torsion angles obtained from
      chemical shifts, we calculated the GB1 structure and obtained a backbone root
      mean-square deviation of 2.0 A from the high-resolution structure of the protein.
      Therefore, this rf-efficient PERSPIRATIONCP method is useful for obtaining many
      long-range distance restraints for protein structure determination.

PMID- 30106586
TI  - Asphaltene Mesoscale Aggregation Behavior in Organic Solvents-A Brownian Dynamics
      Study.
AB  - Significant advances have been achieved in understanding the main molecular
      mechanisms leading to asphaltene aggregation. However, the existing computational
      deficiency of molecular dynamics simulations did not allow full reproduction of
      the complex aggregation behavior of asphaltene in the past. In this work, we use
      the Brownian dynamics simulation to investigate asphaltene aggregation behavior
      on larger length and time scales that have not been previously accessed by
      molecular simulations. This enabled us to completely render the formation of
      clusters of asphaltene nanoaggregates and the resulting fractal or network of
      aggregates during the aggregation process. Asphaltene aggregation is studied at
      several volume fractions (phi = 1-7%) of asphaltene nanoaggregates in two
      solvents including heptane and heptol (i.e., a mixture of heptane and toluene).
      Our simulation results support the aggregation hierarchy proposed in the Yen
      Mullins model (Mullins, Annu. Rev. Anal. Chem. 2011, 4, 393-418.) by
      demonstrating that asphaltene nanoaggregates form small clusters with an
      aggregation number of 7-8 and an average gyration radius of ~4.0 nm capable of
      forming either fractal aggregates with a fractal dimension of 1.93-2.04 at low
      phi or percolating networks of aggregates at high phi. Percolating structures are
      observed at phi = 7% in both solvents. In heptol, the structures mainly percolate
      along two directions, whereas in heptane, they can percolate along three
      directions (i.e., x, y, and z). The self-diffusion coefficient ( D) significantly
      decreases as phi increases. Generally, D is larger in heptol than in heptane, but
      this difference diminishes as phi increases, approaching to almost the same value
      at phi = 7%.

PMID- 30106587
TI  - Nanosecond Tracer Diffusion as a Probe of the Solution Structure and Molecular
      Mobility of Protein Assemblies: The Case of Ovalbumin.
AB  - Protein diffusion is not only an important process ensuring biological function
      but can also be used as a probe to obtain information on structural properties of
      protein assemblies in liquid solutions. Here, we explore the oligomerization
      state of ovalbumin at high protein concentrations by means of its short-time self
      diffusion. We employ high-resolution incoherent quasielastic neutron scattering
      to access the self-diffusion on nanosecond timescales, on which interparticle
      contacts are not altered. Our results indicate that ovalbumin in aqueous (D2O)
      solutions occurs in increasingly large assemblies of its monomeric subunits with
      rising protein concentration. It changes from nearly monomeric toward dimeric and
      ultimately larger than tetrameric complexes. Simultaneously, we access
      information on the internal molecular mobility of ovalbumin on the nanometer
      length scale and compare it with results obtained for bovine serum albumin,
      immunoglobulin, and beta-lactoglobulin.

PMID- 30106588
TI  - Identification of Missing Proteins in Normal Human Cerebrospinal Fluid.
AB  - The cerebrospinal fluid (CSF) proteome data set presented herein was obtained
      after immunodepletion of abundant proteins and off-gel electrophoresis
      fractionation of a commercial pool of normal human CSF; liquid chromatography
      tandem mass spectrometry analysis was performed with a linear ion trap-Orbitrap
      Elite. We report the identification of 12 344 peptides mapping on 2281 proteins.
      In the context of the Chromosome-centric Human Proteome Project (C-HPP), the
      existence of seven missing proteins is proposed to be validated. This data set is
      available to the ProteomeXchange Consortium ( http://www.proteomexchange.org/ )
      with the data set identifier PXD008029.

PMID- 30106589
TI  - Gold-Catalyzed Cascade Reaction of beta-(2-Aminophenyl)-alpha,beta-ynones with
      Ynamides: A Sequential Route to Polysubstituted 2-Aminoquinolines.
AB  - A novel, efficient, and mild synthetic route for the preparation of 2
      aminoquinolines via a gold-catalyzed cascade reaction of beta-(2-aminophenyl)
      alpha,beta-ynones with ynamides has been developed. This process tolerates a wide
      range of functionalities such as halogen, alkyl, aryl, and heteroaryl groups,
      leading to original heterocycles in fair to very good yields.

PMID- 30106590
TI  - Synthesis and Reactivity of N-Allenyl Cyanamides.
AB  - N-Allenyl cyanamides have been accessed via a one-pot deoxycyanamidation
      isomerization approach using propargyl alcohol and N-cyano- N-phenyl- p
      methylbenzenesulfonamide. The utility of this novel class of allenamide was
      explored through derivatization, with hydroarylation, hydroamination, and
      cycloaddition protocols employed to access an array of cyanamide products that
      would be challenging to access using existing methods.

PMID- 30106591
TI  - Exploring Peyer's Patch Uptake as a Strategy for Targeted Lung Delivery of
      Polymeric Rifampicin Nanoparticles.
AB  - Uptake of nanoparticles through Peyer's Patches following oral administration
      could enable translocation through lymph to lymphatic organs like the lungs. An
      important consideration, however, is nanosize and particle hydrophobicity.
      Furthermore, as delivering the nanoparticles to the intestine where the Peyer's
      Patches are localized is important, their intact and rapid transit through the
      stomach into the intestine is highly desirable. We report hydrophobization of
      mucoadhesive Rifampicin-GantrezAN-119 nanoparticles (GzNP) using a hydrophobic
      polymer, ethyl cellulose (EC), with the objectives of augmenting Peyer's Patch
      uptake due to enhanced hydrophobicity and increased intestinal localization as a
      result of decreased mucoadhesion. RIF-Gantrez-EC nanoparticles (ECGzNP2)
      exhibited >13% RIF loading and an average particle size of 400-450 nm, which is
      appropriate for translation through lymph following Peyer's Patch uptake. Higher
      contact angle (67.3 +/- 3.5 degrees  vs 30.3 +/- 2.1 degrees ) and lower
      mucoadhesion (30.7 +/- 4.8 g vs 87.0 +/- 3.0 g) of ECGzNP2 over GzNP confirmed
      hydrophobization and lower mucoadhesion. Fluorescence photomicrographs of
      intraduodenally administered coumarin-labeled RIF-NP in rats demonstrated higher
      Peyer's Patch uptake with ECGzNP2, while the increased lung/plasma RIF ratio
      signified lymph mediated lung targeting. The gastrointestinal transit study in
      rats, which revealed a significantly higher intestine-to-stomach accumulation
      ratio with ECGzNP2 (3.4) compared to GzNP (1.0) [ p < 0.05], confirmed
      availability of the NP in the intestine for Peyer's Patch uptake. Such uptake
      enabled 182.4 +/- 22.6% increase in relative bioavailability, a ~2-fold higher
      plasma AUC/MIC ratio and significantly higher lung concentration with ECGzNP2,
      thereby proposing better efficacy. A significantly higher lung/liver ratio with
      ECGzNP2 also suggested lower hepatic exposure. The repeated dose 28-day oral
      toxicity study demonstrated the safety of the nanocarrier and reduced
      hepatotoxicity with ECGzNP2 compared to RIF. We hereby demonstrate uptake of
      orally administered NP through Peyer's Patches as a feasible strategy for lung
      targeting.

PMID- 30106592
TI  - Atomistic-Level Investigation of a LL37-Conjugated Gold Nanoparticle By Well
      Tempered Metadynamics.
AB  - LL37 is a cathelicidin-derived antimicrobial peptide (AMP) with a broad spectrum
      of antimicrobial activity and wound-healing potential. The enhancement of these
      characteristics was recently demonstrated for a cysteine (CYS)-modified
      cathelicidin-derived LL37-SH conjugated with gold nanoparticles (AuNPs).
      Considering the potential of this peptide, we hereby report a computational study
      in which well-tempered metadynamics was applied to unveil the interaction of LL37
      SH and LL37 with a AuNP with atomistic detail. A structural analysis combined
      with the free energy surface (FES) characterization allowed the assessment of the
      role of CYS residue during the formation of the conjugate, as well as to
      understand how the AuNP improves the antimicrobial activity of the peptide. It
      was found that CYS promotes a lower conformational entropy (before and after
      adsorption onto the AuNP) and a faster adsorption process when compared to the
      LL37 without CYS. The FES for LL37-SH is characterized by one global minimum,
      while for LL37 a potential metastable state was found. The presence of the AuNP
      leads to an elongation of the peptides along with the adsorption, which
      translates into the increase of the solvent-accessible surface area. This
      elongation combined with the greater availability of positively charged residues
      upon adsorption rationalizes the observed enhancement of the activity of the LL37
      SH/AuNP conjugate.

PMID- 30106593
TI  - Catalytic Enantioselective Decarboxylative Mannich-Type Reaction of N-Unprotected
      Isatin-Derived Ketimines.
AB  - The first catalytic enantioselective decarboxylative Mannich-type reaction of N
      unprotected ketimines is reported, directly providing N-unprotected 3
      tetrasubstituted 3-aminooxindoles in high yield and ee without
      protection/deprotection steps. The utility of this reaction is demonstrated in
      the short step synthesis of (+)-AG-041R.

PMID- 30106594
TI  - Multiple-Condition Analysis in a Retrievable Subcutaneous Animal Model for Drug
      Screening on Full Pancreatic Tissue Digest.
AB  - The lack of understanding on how to treat pancreas-related diseases and develop
      new therapeutics is partly due to the unavailability of appropriate models. In
      vitro models fail to provide a physiological environment. Testing new drug
      targets in these models can give rise to bias and misleading results. Therefore,
      we developed an in vivo model for drug testing on full pancreatic digests, which
      maintains the interactions between endo- and exocrine tissues and allows
      retrieving the samples for further analyses. The use of full pancreatic digest
      eliminates the need to isolate islets, reducing time and cost. In this model,
      four different conditions can be implanted subcutaneously within the same animal.
      Each condition consists of full pancreatic tissue digests embedded in alginate
      beads. All alginate beads in one animal contained full pancreatic digest of the
      same donor and, after 5-day implantation, were retrieved for analysis focusing on
      survival, function, and/or organization. Proof-of-principle of the platform was
      evidenced by showing the effect of hyaluronic acid and vascular endothelial
      growth factor on the overall function of the full pancreatic digest and on
      endothelial cells in the pancreatic digest, respectively. Retrieval from
      identical animals allows direct comparison between conditions. Metabolism (MTT)
      quantification, dithizone staining, and glucose-stimulated insulin secretion
      assessment allow to discriminate, using a minimal number of animals, between
      treatments and validate the system. Because of its simplicity, the model is
      highly adaptable to specific needs of the user.

PMID- 30106595
TI  - Utilizing progress testing in a competency-based medical education curriculum.

PMID- 30106596
TI  - Therapeutic Engagement of the Histone Deacetylase IIA-Myocyte Enhancer Factor 2
      Axis Improves Experimental Pulmonary Hypertension.

PMID- 30106597
TI  - Assessing learning in the adaptive curriculum.
AB  - BACKGROUND: Medical education is a dynamic process that will continuously evolve
      to respond to changes in the foundations of medicine, the clinical practice of
      medicine and in health systems science. PURPOSE: In this paper, we review how
      assessing learning in such a dynamic environment requires comprehensive flexible
      and adaptable methodological approaches designed to assess knowledge attainment
      and transfer, clinical skills/competency development, and ethical/professional
      behavior. Adaptive assessments should measure the learner's ability to observe
      where changes in health care delivery are needed and how to implement them.
      Balancing formative and summative assessments will promote reflective learning so
      that each student will reach her/his highest potential. From the programmatic
      perspective, measuring the design and delivery of instruction in relation to
      students? efforts to achieve competency will improve learning and foster
      continuous professional development of faculty and advance the science of
      learning. APPROACH: We describe how two medical schools are approaching adaptive
      assessment, including using portfolio systems that encompass teaching and
      learning experiences while offering real-time longitudinal tracking of digital
      data toward improving learning and provide curricula continuous improvement
      cycles. Using latest technologies, portfolios produce actionable data displays
      with precise guidance for learning and program development.

PMID- 30106598
TI  - 4',6-Diamidino-2-Phenylindole Distinctly Labels Tau Deposits.
AB  - Tau deposits have distinct biochemical characteristics and vary morphologically
      based on identification with tau antibodies and several chemical dyes. Here, we
      report 4',6-diamidino-2-phenylindole (DAPI)-positivity of tau deposits.
      Furthermore, we investigated the cause for this positivity. DAPI was positive in
      3R/4R (3-repeat/4-repeat) tau deposits in Alzheimer's disease, myotonic
      dystrophy, and neurodegeneration with brain iron accumulation, and in 4R tau
      deposits in corticobasal degeneration, but negative in 4R tau deposits in
      frontotemporal dementia with parkinsonism-17 and progressive supranuclear palsy.
      The peak emission wavelength of DAPI after binding to a tau deposit was similar
      to that after binding to a nucleus. This DAPI-positivity was conspicuous at the
      optimum concentration of 2 MUg/ml. DAPI-positivity was diminished after formic
      acid treatment, but preserved after nucleic acid elimination and phosphate moiety
      blocking. Our results suggest that staining with 2 MUg/ml DAPI is a common but
      useful tool to differentially detect tau deposits in various tauopathies.

PMID- 30106599
TI  - Pharmacokinetic evaluation of meropenem and vaborbactam for the treatment of
      urinary tract infection.
AB  - INTRODUCTION: Meropenem/vaborbactam (M/V) represents the first carbapenem and
      beta-lactamase inhibitor combination approved for treatment of complicated
      urinary tract infections (cUTIs), including pyelonephritis. Vaborbactam is a
      novel boronic acid, beta-lactamase inhibitor with a high affinity for serine beta
      lactamases, including Klebsiella pneumoniae carbapenemase (KPC). This
      combination, VabomereTM, was approved in August 2017 by the United States Food
      and Drug Administration for the treatment of cUTIs in patients 18 years or older,
      including pyelonephritis, caused by the following susceptible microorganisms:
      Escherichia coli, K. pneumoniae, and Enterobacter cloacae species complex. Areas
      covered: Relevant literature regarding microbiology, pharmacokinetics,
      pharmacodynamics, and clinical trials evaluating efficacy, safety, and
      tolerability will be discussed. Expert opinion: Current treatment options for KPC
      producing infections such as aminoglycosides, polymyxins, fosfomycin, and
      tigecycline are associated with concerns regarding efficacy, toxicities, optimal
      dosing, and/or development of resistance. Additionally, resistance to the new
      combination product of ceftazidime/avibactam has also emerged. Current clinical
      evidence supporting the use of M/V for KPC-producing infections is limited to an
      open-label, randomized, phase III study in a small number of patients with
      serious infections due to carbapenem-resistant Enterobacteriaceae. Although M/V
      is not approved for KPC-producing infections, we believe that M/V will become a
      preferred agent for KPC-producing Enterobacteriaceae infections.

PMID- 30106600
TI  - Stabilization of Acute High-Grade Acromioclavicular Joint Separation: A
      Prospective Assessment of the Clavicular Hook Plate Versus the Double Double
      Button Suture Procedure.
AB  - BACKGROUND: The stabilization strategy for acute high-grade acromioclavicular
      (AC) joint separations with AC-stabilizing clavicular hook plate (cHP) or
      coracoclavicular (CC)-stabilizing double double-button suture (dDBS) is still
      under consideration. HYPOTHESIS: The CC-stabilizing dDBS is superior to the cHP
      according to an AC-specific radiologic assessment and score system. STUDY DESIGN:
      Cohort study; Level of evidence, 2. METHODS: Seventy-three consecutive patients
      with acute high-grade AC joint separation were prospectively followed in 2
      treatment groups (64.4% randomized, 35.6% patient-selected treatment): open
      reduction and cHP (cHP group) or arthroscopically assisted dDBS (dDBS group)
      performed within 14 days of injury. Patients were prospectively analyzed by
      clinical scores (Taft, Constant score [CS], numeric analog scale for pain) and AC
      specific radiographs (AC distance, CC distance [CCD], relative CCD [rCCD; 100 /
      AC distance * CCD]) at points of examination (preoperative and 6, 12, and 24
      months). The minimal clinically important differences (MCIDs) were assessed by
      the anchor-based method. RESULTS: Twenty-seven of 35 patients (mean age +/- SD:
      37.7 +/- 9.7 years) after cHP implantation and 29 of 38 patients (34.2 +/- 9.7
      years) after dDBS implantation were continuously followed until the 24-month
      follow-up. All patients showed significantly increased scores after surgery as
      compared with preoperative status (all P < .05). As compared with GI, GII had
      significantly better outcomes at 24 months (Taft: cHP = 9.4 +/- 1.7 vs dDBS =
      10.9 +/- 1.1, P < .05, MCID = 2.9; CS: cHP = 90.2 +/- 7.8 vs dDBS = 95.3 +/- 4.4,
      P < .02, MCID = 16.6) and at 24 months for Rockwood IV/V (Taft: cHP = 9.4 +/- 1.7
      vs dDBS = 11.1 +/- 0.8, P < .0005; CS: cHP = 90.1 +/- 7.7 vs dDBS = 95.5 +/- 3.1,
      P < .04). Clinically assessed horizontal instability persisted in 18.52% (GI) and
      6.89% (GII; P = .24). The rCCD showed equal loss of reduction at 24 months (GII =
      130.7% [control = 111%] vs GI = 141.8% [control = 115%], MCID = 11.1%).
      CONCLUSION: This prospective study showed significantly superior outcomes in all
      clinical scores between GII and GI. The subanalysis of the high-grade injury type
      (Rockwood IV/V) revealed that these patients showed significant benefits from the
      dDBS procedure in the clinical assessments. The cHP procedure resulted in good to
      excellent clinical outcome data and displayed an alternative procedure for
      patients needing less restrictive rehabilitation protocols.

PMID- 30106602
TI  - Nuclear localized Raf1 isoform alters DNA-dependent protein kinase activity and
      the DNA damage response.
AB  - Raf1/c-Raf is a well-characterized serine/threonine-protein kinase that links Ras
      family members with the MAPK/ERK signaling cascade. We have identified a novel
      splice isoform of human Raf1 that causes protein truncation and loss of the C
      terminal kinase domain (Raf1-tr). We found that Raf1-tr has increased nuclear
      localization compared with full-length Raf1, and this finding was secondary to
      reduced binding of Raf1-tr to the cytoplasmic chaperone FK506 binding protein 5.
      We show that Raf1-tr has increased binding to DNA-dependent protein kinase (DNA
      PK), which inhibits DNA-PK function and causes amplification of irradiation- and
      bleomycin-induced DNA damage. We found that the human colorectal cancer cell
      line, HCT-116, displayed reduced expression of Raf1-tr, and reintroduction of
      Raf1-tr sensitized the cells to bleomycin-induced apoptosis. Furthermore, we
      identified differential Raf1-tr expression in breast cancer cell lines and showed
      that breast cancer cells with increased Raf1-tr expression become sensitized to
      bleomycin-induced apoptosis. Collectively, these results demonstrate a novel Raf1
      isoform in humans that has a unique noncanonical role in regulating the double
      stranded DNA damage response pathway through modulation of DNA-PK function.
      Nixon, B. R., Sebag, S. C., Glennon, M. S., Hall, E. J., Kounlavong, E. S.,
      Freeman, M. L., Becker, J. R. Nuclear localized Raf1 isoform alters DNA-dependent
      protein kinase activity and the DNA damage response.

PMID- 30106601
TI  - The Metabolic Syndrome and Health Behaviors in School Children Aged 13-16 Years
      in Ubon Ratchathani: UMeSIA Project.
AB  - BACKGROUND: Although metabolic syndrome (MetS) has become a significant public
      health problem worldwide, little evidence exists to describe the prevalence of
      MetS in school children using MetS different classifications, and its association
      with health-related behaviors. METHODS: Using data on 393 children and
      adolescents aged 13-16 years participating in the Ubon Ratchathani Metabolic
      Syndrome in Adolescent (UMeSIA) Project, the prevalence of MetS was determined
      using the International Diabetes Federation (IDF) 2007 definition and other three
      classifications reported in the previous literature. The prevalence of the MetS
      was compared across sex, a family history of diabetes, type of schools, and
      health behaviors using chi-square test. The prevalence of MetS and proportion of
      abnormalities in MetS components were compared across different MetS
      classifications using Cochran Q test. RESULTS: The prevalence of MetS in Thai
      school children was 3.1%, 5.8%, 6.9%, and 11.2% when using IDF, Cook's, Ford's,
      and De Ferranti's classifications respectively (Difference in MetS prevalence
      across the four MetS classifications, P < 0.001). Using IDF classification,
      prevalence was higher in male than female students (5.9% and 1.2%, respectively,
      P < 0.001) and higher in those with a family history of diabetes than those
      without (8.5% and 2.3%, respectively, P < 0.001). Students from a sports school
      had considerably lower MetS prevalence than those from conventional schools (1.9%
      and 3.5% respectively, P < 0.001). Those with MetS spent significantly longer
      time watching TV than those without (median (interquartile range) time to watch
      TV 180.0 (120.0, 240.0) and 120.0 (60.0, 180.0) min per day respectively, P =
      0.002). CONCLUSIONS: The prevalence of MetS in Thai school children was modest
      and varied greatly when different MetS definitions were applied. Interventions to
      optimize time spent watching TV and increase physical activity may be beneficial
      in reducing the risk of the MetS in children and adolescents.

PMID- 30106603
TI  - Curative Effect of Digestive Tract Reconstruction After Radical Gastrectomy for
      Distal Gastric Cancer.
AB  - OBJECTIVE: Short-term complications and long-term prognoses of three kinds of
      digestive tract reconstructions after radical gastrectomy for distal gastric
      cancer were compared. MATERIALS AND METHODS: Patients who underwent radical
      gastrectomy for distal gastric cancer were divided into three groups according to
      the type of digestive tract reconstruction: Billroth I, Billroth II, and Roux-en
      Y anastomosis. Clinicopathological characteristics, intraoperative conditions,
      short-term complications, and long-term prognoses were compared among the three
      groups. RESULTS: There were no significant differences in the clinicopathological
      characteristics and postoperative complications among the three groups (P > .05).
      There was no significant difference in the operative times of the Billroth I and
      Billroth II anastomosis groups, but the operative times in both groups were
      shorter than the operative time in the Roux-en-Y anastomosis group (P < .05). The
      5-year overall survival (OS) rate in the Billroth I, Billroth II, and Roux-en-Y
      anastomosis groups was 58.3%, 55.0%, and 62.2%, respectively, with no significant
      difference among the three groups. There was no significant difference in the OS
      rate according to the tumor node metastasis stage among the three groups (P >
      .05). CONCLUSION: The postoperative complications and prognoses were similar in
      the different digestive tract reconstruction groups. Billroth I anastomosis is a
      simple surgical method that can be used for gastrointestinal reconstruction after
      distal gastrectomy.

PMID- 30106604
TI  - Response to Yu et al. Article "Healthcare Resource Waste Associated with Patient
      Nonadherence and Early Discontinuation of Traditional Continuous Glucose
      Monitoring in Real-World Settings: A Multicountry Analysis".

PMID- 30106605
TI  - Pharmacotherapy for erectile dysfunction in diabetic males.
AB  - INTRODUCTION: Numerous studies have highlighted the intimate association between
      erectile dysfunction (ED) and diabetes mellitus (DM). However, the true
      pathogenesis of ED among diabetic men has not yet been fully discovered. The
      treatment of ED in diabetic patients remains an interesting area of research. The
      last two decades have witnessed phenomenal advances in the management of ED with
      the efficacy of pharmacotherapy for ED in diabetic patients encouraging,
      especially with introduction of innovative conservative tools for treatment.
      Areas covered: The aim of this review is to discuss the currently available
      information on ED pharmacotherapy in diabetic males and provide an expert
      perspective on the current treatment strategies. Expert opinion: Conservative
      treatment remains the initial step for the treatment of ED in diabetic patients.
      This kind of therapy consists of different modalities including: oral treatments,
      intracavernosal pharmacotherapy, and evolving modalities such as soluble
      guanylate cyclase activators, stem cells (SCs), and alternative treatments such
      as herbal treatment and transdermal/topical pharmacotherapy. However, it should
      be noted that the currently available pharmacotherapy is still far from ideal.
      One hopes to witness new drugs and technologies that may revolutionize ED
      treatment in the future, especially in such complex cases as DM.

PMID- 30106606
TI  - A Multi-institutional Propensity Score Matched Comparison of Transperitoneal and
      Retroperitoneal Partial Nephrectomy for cT1 Posterior Tumors.
AB  - OBJECTIVE: To compare the perioperative and renal functional outcome between
      transperitoneal and retroperitoneal robotic partial nephrectomy (TP-RPN and RP
      RPN) in the largest cohort to date of RP-RPN for posterior tumors. METHODS: We
      identified 519 patients who met eligibility criteria and underwent TP-RPN (n =
      357, 68.8%) or RP-RPN (n = 162, 31.2%) for a posteriorly located cT1 tumor.
      Patients were propensity score (PS) matched on preoperative and tumor-specific
      characteristics. Perioperative outcome and renal function outcome at median
      follow-up 22 months were compared. RESULTS: Between the PS matched TP-RPN (n =
      157, 50%) and RP-RPN (n = 157, 50%) patients, operative time (OT) (185.0 versus
      157.0, P < .001) was longer in TP-RPN versus RP-RPN patients. No significant
      differences in ischemia time (P = .618), blood loss (P = .178), positive surgical
      margins (P = .501), overall postoperative complications (P = .861), or
      progression of chronic kidney disease stage at median 22 months (P = .599) were
      identified. Length of stay (LOS) was reduced in RP-RPN patients (P = .017), but
      was not different once an institution used a postoperative day (POD)-1 discharge
      protocol (P = .579). Operative times were similar between groups in patients with
      obesity (P = .293) or a cT1b renal mass (P = 908). CONCLUSION: RP-RPN for
      posterior tumors resulted in reduced OT and a shorter LOS compared to TP-RPN.
      When surgeons aimed to routinely discharge patients on POD-1, the surgical
      approach did not influence LOS. Operative time was similar between RP and TP-RPN
      among patients with obesity or a cT1b renal mass. All other measures, including
      ischemia time, blood loss, margin rates, complications, and renal function, did
      not differ between the two approaches.

PMID- 30106607
TI  - Don't forget healthcare workers are required to have other mandatory
      immunizations, so why isn't the influenza vaccination included?

PMID- 30106608
TI  - Progression to chronic kidney disease in patients undergoing nephrectomy for
      small renal masses: a price to pay for a therapeutic success?
AB  - Nephrectomy, which constitutes a gold-standard procedure for the treatment of
      renal-cell carcinoma (RCC), has been widely discussed in the past decade as a
      significant risk factor of the development of chronic kidney disease (CKD). RCC
      is the third most common genitourinary cancer in the United States, with an
      estimated more than 65,000 new cases and 14,970 deaths. The aim of this review
      was to precisely and comprehensively summarize the status of current knowledge in
      CKD risk factors after nephrectomy, the advantages of minimally invasive vs.
      radical nephrectomy, post-nephrectomy biomarkers of CKD, ways of post-operative
      CKD prevention and, therefore, better understand why various aspects of CKD after
      nephrectomy. The majority of current studies indicated a better long-term kidney
      function preservation in patients undergoing partial nephrectomy in comparison to
      those after radical nephrectomy. Furthermore, a nephron-sparing surgery should be
      a preferred first-line procedure among young patients with small renal masses. As
      partial nephrectomy is followed by a greater risk of adverse outcomes relative to
      radical nephrectomy, a potential survival benefit should always be considered
      especially in the elderly or patients with comorbidities.

PMID- 30106609
TI  - Does Extended PET Acquisition in PET/MRI Rectal Cancer Staging Improve Results?
AB  - OBJECTIVE: The purpose of this study was to determine if extended PET acquisition
      times in the pelvis during PET/MRI increase detection rates of potentially
      metastatic lymph nodes in patients with rectal cancer. MATERIALS AND METHODS: Our
      study was approved by the institutional review board of the University of
      California, San Francisco. Twenty-two patients with biopsy-proven rectal cancer
      underwent imaging via simultaneous 3-T time-of-flight PET/MRI, with seven
      undergoing two separate PET/MRI examinations, for a total of 29 studies. Each
      examination included both a whole-body PET/MRI and a dedicated pelvic PET/MRI
      with both 3- and 15-minute PET acquisitions for the pelvis. Three radiologists
      interpreted each examination with PET only, MRI only, then combined PET and MRI
      examinations, using all available images. Additionally, the 3- and 15-minute PET
      acquisitions of the pelvis were reviewed separately by a single radiologist.
      RESULTS: A total of 94 lymph nodes were identified as abnormal on PET, all with
      MRI anatomic correlates. Of these, 37 (39.4%) were seen only on the dedicated 15
      minute acquisition. Fifty-seven (60.6%) nodes measured 5 mm or less, including 29
      (30.9%) seen only on the 15-minute acquisition. Thirty-one (33.0%) nodes measured
      5.1-10 mm, including eight (25.8%) seen only on the 15-minute acquisition. Of the
      17 subjects imaged for initial staging, 11 (64.7%) were upstaged as a result of
      the increased PET acquisition time (10 from N1 to N2 and one from N0 to N1).
      CONCLUSION: Longer PET acquisition times during PET/MRI for rectal cancer
      increases the number of FDG-avid lymph nodes detected without increasing scan
      time.

PMID- 30106610
TI  - Optoacoustic Breast Imaging: Imaging-Pathology Correlation of Optoacoustic
      Features in Benign and Malignant Breast Masses.
AB  - OBJECTIVE: Optoacoustic ultrasound breast imaging is a fused anatomic and
      functional modality that shows morphologic features, as well as hemoglobin amount
      and relative oxygenation within and around breast masses. The purpose of this
      study is to investigate the positive predictive value (PPV) of optoacoustic
      ultrasound features in benign and malignant masses. SUBJECTS AND METHODS: In this
      study, 92 masses assessed as BI-RADS category 3, 4, or 5 in 94 subjects were
      imaged with optoacoustic ultrasound. Each mass was scored by seven blinded
      independent readers according to three internal features in the tumor interior
      and two external features in its boundary zone and periphery. Mean and median
      optoacoustic ultrasound scores were compared with histologic findings for
      biopsied masses and nonbiopsied BI-RADS category 3 masses, which were considered
      benign if they were stable at 12-month follow-up. Statistical significance was
      analyzed using a two-sided Wilcoxon rank sum test with a 0.05 significance level.
      RESULTS: Mean and median optoacoustic ultrasound scores for all individual
      internal and external features, as well as summed scores, were higher for
      malignant masses than for benign masses (p < 0.0001). High external scores,
      indicating increased hemoglobin and deoxygenation and abnormal vessel morphologic
      features in the tumor boundary zone and periphery, better distinguished benign
      from malignant masses than did high internal scores reflecting increased
      hemoglobin and deoxygenation within the tumor interior. CONCLUSION: High
      optoacoustic ultrasound scores, particularly those based on external features in
      the boundary zone and periphery of breast masses, have high PPVs for malignancy
      and, conversely, low optoacoustic ultrasound scores have low PPV for malignancy.
      The functional component of optoacoustic ultrasound may help to overcome some of
      the limitations of morphologic overlap in the distinction of benign and malignant
      masses.

PMID- 30106611
TI  - Attenuation and Degree of Enhancement With Conventional 120-kVp Polychromatic CT
      and 70-keV Monochromatic Rapid Kilovoltage-Switching Dual-Energy CT in Cystic and
      Solid Renal Masses.
AB  - OBJECTIVE: The purpose of this study was to compare attenuation values (in
      Hounsfield units) and degree of enhancement (attenuation change) in renal masses
      using 120-kVp polychromatic (conventional) CT and 70-keV monochromatic dual
      energy CT (DECT). MATERIALS AND METHODS: Twenty-two patients with 39 renal masses
      (24 Bosniak category I and II cysts and 15 solid masses under active
      surveillance) underwent conventional CT (120-kVp unenhanced and contrast-enhanced
      CT) and rapid kilovoltage-switching DECT (120-kVp unenhanced CT and 70-keV
      contrast-enhanced CT). The mean (+/- SD) time between scans was 648 +/- 943 days.
      A radiologist measured attenuation on matched image sets coregistered between
      examinations. Absolute attenuation and attenuation change were compared using
      independent t tests, Pearson correlation, and Bland-Altman analysis. RESULTS:
      There was no difference in attenuation on 120-kVp versus 70-keV contrast-enhanced
      CT images for cysts (9.5 +/- 5.5 HU [range, -2 to 20 HU] vs 10.1 +/- 4.6 HU
      [range, -2 to 16 HU]; p = 0.33) and solid masses (110.1 +/- 72.9 HU [range, 35
      267 HU] vs 119.1 +/- 73.7 HU [range, 33-265 HU]; p = 0.04). There also was no
      difference in attenuation change for 120-kVp contrast-enhanced CT minus 120-kVp
      unenhanced CT (cysts, 3.5 +/- 3.9 HU [range, -2 to 13 HU]; solid masses, 80.7 +/-
      73.3 HU [range, 9-227 HU]; p = 0.45) or for 70-keV contrast-enhanced CT minus 120
      kVp unenhanced CT (cysts, 4.3 +/- 4.1 HU [range, -3 to 12 HU]; solid masses, 89.8
      +/- 74.1 HU [range, 7-226 HU]; p = 0.04). The correlation was strong to almost
      perfect (beta = 0.83-0.98) with substantial agreement. There was no difference in
      attenuation of cysts and solid masses comparing 120-kVp acquisitions acquired at
      different time points (p = 0.20-0.92). The correlation was strong to almost
      perfect (beta = 0.72-0.95) with substantial agreement. CONCLUSION: There are no
      differences in absolute attenuation or degree of enhancement comparing 70-keV
      monochromatic CT to conventional 120-kVp CT in renal cysts and solid masses.

PMID- 30106612
TI  - Practical Imaging Strategies for Acute Appendicitis in Children.
AB  - OBJECTIVE: Diagnosing pediatric appendicitis is difficult because clinical
      findings are nonspecific. Improved accuracy can be obtained with ultrasound (US),
      CT, or MRI, despite considerable variation in their use at different
      institutions. This article reviews the evidence for best practices in imaging
      pediatric appendicitis. CONCLUSION: When each modality is optimally used, a
      stepwise imaging approach that begins with graded compression US and proceeds to
      CT or MRI in select cases is currently best practice.

PMID- 30106613
TI  - Evaluation of Gadolinium Deposition in the Brain After MR Arthrography.
AB  - OBJECTIVE: Although significant investigation has been done into the deposition
      of gadolinium in the brains of patients receiving IV gadolinium, there is little
      research concerning nonintravenous uses of gadolinium, specifically in
      conjunction with musculoskeletal MR arthrography. Although small in volume,
      intraarticular administration is an off-label use of gadolinium, necessitating
      careful scrutiny for patient safety. Thus, we investigated the relationship
      between intraarticular gadolinium administration during MR arthrography and the
      presence of intracranial gadolinium deposition on subsequent brain MRI. MATERIALS
      AND METHODS: An institutional review board-approved retrospective study was
      performed of patients with no history of gadolinium exposure who underwent MR
      arthrography from 2006 to 2016 followed by an unenhanced brain MRI examination.
      ROIs were manually placed within bilateral dentate nuclei (DN), bilateral globus
      pallidi (GP), bilateral thalami, bilateral middle cerebral peduncles (MCP), and
      the central pons (CP) on T1-weighted sequences. The left and right ROIs were
      averaged, and ratios of signal intensity were calculated for DN/MCP, DN/CP,
      GP/MCP, GP/CP, thalamus/MCP, and thalamus/CP. Similar ROIs were placed and ratios
      calculated for age-matched control subjects who had a history of brain MRI but no
      prior gadolinium exposure. We used t testing to compare signal intensity ratios
      between patients and control subjects. RESULTS: A total of 31 patients met the
      inclusion criteria. We found no significant difference in signal intensity
      between patients and control subjects for DN/MCP (p = 0.40), DN/CP (p = 0.76),
      GP/MCP (p = 0.51), GP/CP (p = 0.86), thalamus/MCP (p = 0.93), and thalamus/CP (p
      = 0.30). CONCLUSION: No association was found between intraarticular gadolinium
      administration for MR arthrography and detectable gadolinium deposition within
      the brain.

PMID- 30106614
TI  - Benefit of a Visual Aid in the Management of Moderate-Severity Contrast Media
      Reactions.
AB  - OBJECTIVE: The purpose of this study was to compare management of moderate
      severity reactions with and without a visual aid or flowchart in contrast medium
      reaction simulations. SUBJECTS AND METHODS: All attending radiologists and
      trainees were requested to participate in a contrast medium reaction simulation
      program, including a moderate-severity reaction scenario, and were randomized to
      groups having or not having a visual aid. The time to administer intramuscular
      (IM) epinephrine via automated injector and errors in administration were
      recorded. After the simulation, all participants completed a survey assessing
      their comfort in treating reactions to contrast media with and without a visual
      aid. RESULTS: A total of 138 participants were divided into 21 sessions in the
      program, with 68 participants in the moderate-severity reaction scenario. Eleven
      groups were provided a visual aid; 10 groups were not. Errors in management
      occurred in 18.2% (2 of 11) of groups with visual aids versus 40% (4 of 10) in
      groups without (p = 0.35), with epinephrine self-administration reflecting the
      most common error. Excluding the groups with errors, the mean time to
      administration of IM epinephrine was 97 seconds with versus 152 seconds without
      the visual aid (p = 0.04). Of the 138 participants, 97.8% agreed that the poster
      would aid in medication administration, and 87% agreed that it would help
      decrease time to administer medications. CONCLUSION: A visual aid increased the
      subjective confidence of radiologists in the dose and route of medication
      administration in the contrast medium reaction simulation and led to faster
      administration of epinephrine. Self-administration IM epinephrine errors were
      common and seen in both groups.

PMID- 30106615
TI  - Diagnostic Performance of Transient Elastography for Liver Fibrosis in Children:
      A Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: We aimed to assess the diagnostic performance of transient
      elastography for evaluating liver fibrosis in children and adolescents. MATERIALS
      AND METHODS: A computerized search of Medline and Embase up to December 31, 2017,
      was performed to identify studies. Studies evaluating the diagnostic performance
      of transient elastography for the severity of liver fibrosis in children and
      adolescents were selected. Pooled sensitivity and specificity were calculated
      using hierarchic logistic regression modeling. Multiple subgroup analysis was
      performed. RESULTS: In this meta-analysis that included 11 original articles
      involving 723 patients, transient elastography showed a summary sensitivity of
      95% (95% CI, 74-99%) and a specificity of 90% (95% CI, 81-95%) for the diagnosis
      of significant liver fibrosis (stage >= F2) in children. The hierarchic summary
      ROC AUC was 0.96 (95% CI, 0.94-0.98). Multiple subgroup analysis for the
      diagnosis of significant hepatic fibrosis showed clinically acceptable ranges of
      sensitivity and specificity across all subgroups. In additional subgroup
      analysis, the diagnostic accuracies of transient elastography according to the
      Metavir system were also within a clinically acceptable range, measured up to a
      sensitivity of 86% and specificity of 86% for diagnosing Metavir stage F4
      fibrosis. CONCLUSION: Transient elastography showed highly accurate diagnostic
      performance for the diagnosis of liver fibrosis in children.

PMID- 30106616
TI  - Nipple Discharge: Imaging Variability Among U.S. Radiologists.
AB  - OBJECTIVE: The purpose of this study was to assess radiologists' choice of
      imaging modality for the evaluation of clinical symptoms of physiologic nipple
      discharge (e.g., bilateral discharge, multiple-duct orifices, and yellow, green,
      or white color) and pathologic nipple discharge (e.g., unilateral discharge,
      single-duct orifices, spontaneous and serous discharge, and clear or bloodstained
      color). MATERIALS AND METHODS: An online survey was sent to lead interpreting
      physicians at mammography facilities accredited by the American College of
      Radiology (ACR). Statistical analysis was performed using chi-square tests for
      frequency data and multinomial logistic regression. RESULTS: A total of 849
      responses to 8170 distributed surveys were received, for a response rate of
      10.4%. For the workup of physiologic nipple discharge, 30% of respondents
      recommended screening mammography (SM); 24%, diagnostic mammography (DM) only;
      and 46%, both DM and targeted ultrasound (US) (DM plus US). For the workup of
      physiologic nipple discharge, practitioners in nonacademic settings and those who
      read breast images during less than 50% of their practice were significantly more
      likely to recommend DM (with or without US), compared with SM (the standard
      recommended by the ACR). Those reading breast images less than 50% of the time
      were also more likely to recommend MRI after conventional imaging revealed
      negative results. For the workup of pathologic nipple discharge, 91.0% of
      respondents recommended DM plus US; 8.5%, DM only; and fewer than 1.0%, SM.
      Nonacademic providers and those who read breast images less than 50% of the time
      were significantly less likely to recommend DM plus US (the standard recommended
      by the ACR), compared with DM only. CONCLUSION: The present study shows
      variability in imaging modality selection among U.S. radiologists handling the
      imaging workflow for benign and pathologic nipple discharge. Radiologists do not
      uniformly follow ACR practice guidelines, which potentially leads to unnecessary
      workups and extra health care costs.

PMID- 30106617
TI  - Application of Cinematic Rendering in Clinical Routine CT Examination of Ankle
      Sprains.
AB  - OBJECTIVE: Cinematic rendering technique is used to generate almost
      photorealistic 3D reconstructions of volumetric data. The purpose of this study
      was to evaluate the feasibility of cinematically rendered reconstructions in
      routine CT examinations of ankle sprains. CONCLUSION: Cinematic rendering
      technique may be primarily used to deliver visual information to patients,
      physicians, and virtual anatomy classes. Postprocessing requires more time than
      traditional methods do, which can be a hindrance in clinical work.

PMID- 30106618
TI  - Diagnostic Accuracy of MRI for Diagnosis of Internal Hernia in Pregnant Women
      With Prior Roux-en-Y Gastric Bypass.
AB  - OBJECTIVE: The purpose of this study was to evaluate the accuracy of MRI for the
      diagnosis of internal hernia (IH) in pregnant women who have undergone Roux-en-Y
      gastric bypass (RYGB). MATERIALS AND METHODS: Fifteen consecutively registered
      pregnant women (eight with surgically proven IH, seven without IH) who had
      previously undergone RYGB underwent MRI to rule out IH between July 2011 and July
      2016. Two blinded radiologists retrospectively evaluated MRI examinations for the
      presence or absence of 13 established CT findings of IH. The final diagnosis of
      IH was evaluated subjectively and with two previously validated CT models (model
      1, mesenteric swirl or small-bowel obstruction; model 2, beaking of the superior
      mesenteric vein or small-bowel obstruction). Diagnostic odds ratio (DOR) and
      interobserver agreement were calculated for each feature, and the subjective and
      model-based diagnoses of IH were compared by chi-square test. RESULTS: There were
      no statistically significant differences in patient age (p = 0.68), gestational
      age (p = 0.35), or time since RYGB (p = 0.55) between patients with and those
      without IH. The findings with best DOR and interobserver agreement were beaking
      of the superior mesenteric vein (reader 1 DOR, 39; reader 2 DOR, 39; kappa =
      1.00), mesenteric swirl (reader 1 DOR, 11; reader 2 DOR, 39; kappa = 0.86),
      engorgement of mesenteric vessels (reader 1 DOR, 24; reader 2 DOR, 15; kappa =
      0.84), and mesenteric edema (reader 1 DOR, 11; reader 2 DOR, 3; kappa = 0.73).
      The other findings had either low accuracy, poor interobserver agreement, or
      both. The overall sensitivity and specificity of the diagnosis of IH ranged from
      75% to 88% and 86% to 100% for the two readers. There was no difference in
      diagnostic accuracy between the three methods (p = 0.93). CONCLUSION: MRI is
      useful in the diagnosis of IH in pregnant women who have undergone RYGB. The
      specificity is comparable to that of CT, and the sensitivity approaches that of
      CT.

PMID- 30106619
TI  - Part-Time Pediatric Radiology: The Realities and Perceptions of Part-Time
      Employment in the Academic Setting.
AB  - OBJECTIVE: The goal of this study is to evaluate the perceptions held by full-
      and part-time academic pediatric radiologists with regard to the value of part
      time radiologists, as well as the value placed on the work of part-time
      colleagues by their departments and institutions. MATERIALS AND METHODS: Two
      online surveys were distributed to full- and part-time pediatric radiologists via
      the Society for Pediatric Radiology e-mail list serve. Survey questions evaluated
      demographic data of both full- and part-time radiologists, as well as the
      perceptions each group has of part-time employment. RESULTS: Part-time
      radiologists reported significantly greater work-life balance than did their full
      time counterparts and were less likely to report job dissatisfaction. Full- and
      part-time faculty have comparable levels of perceived departmental contributions.
      Part-time faculty were more likely to be younger women, early in their careers,
      and older men nearing retirement. CONCLUSION: Part-time employment provides
      perceived benefits of increased work-life balance and job satisfaction and is
      viewed favorably by both full- and part-time radiologists in academic settings.

PMID- 30106620
TI  - Endogenous glucose production following sequential meals in humans: evidence for
      more prolonged suppression following ingestion of a second meal.
AB  - Single meal studies have shown that carbohydrate ingestion causes rapid and
      persistent suppression of endogenous glucose production (EGP). However, little is
      known about the regulation of EGP under real-life eating patterns where multiple
      carbohydrate-containing meals are consumed throughout the day. Therefore, we
      aimed to characterize the regulation of EGP in response to sequential meals,
      specifically during the breakfast-lunch transition. Nine healthy individuals (5
      males, 4 females; 32 +/- 2 years; 25.0 +/- 1.4 kg/m2) ingested two identical
      mixed meals, each containing 25 g of glucose, separated by 4 h and EGP was
      determined using the variable infusion tracer-clamp approach. EGP was rapidly
      suppressed after both meals, with the pattern and magnitude of suppression being
      similar over the initial 75 min post-meal period. However, EGP suppression was
      more transient after breakfast compared to lunch, with EGP returning to basal
      rates 3 h after breakfast. In contrast, EGP remained in a suppressed state for
      the entire 4 h post-lunch period. This occurred despite each meal eliciting
      similar plasma glucose and insulin responses. However, there was greater
      suppression of plasma glucagon levels after lunch, likely contributing to this
      response. These findings highlight the potential for distinct regulation of EGP
      with each meal of the day and suggest that EGP may be in a suppressed state for
      much of the day, since EGP did not return to basal rates even after a lunch meal
      containing a modest amount of carbohydrate.

PMID- 30106622
TI  - Cardiac Branched-Chain Amino Acid Oxidation is Reduced During Insulin Resistance
      in the Heart.
AB  - Recent studies have proposed that elevated branched-chain amino acids (BCAAs) may
      induce insulin resistance (IR) in muscle secondary to increased BCAA oxidation
      inhibiting glucose oxidation (GO) and fatty acid oxidation (FAO). However, BCAA
      oxidation rates have not been assessed in muscle IR and cardiac FAO rates are
      elevated in obesity-associated IR. We examined cardiac BCAA oxidation in mice fed
      a high fat diet (HFD) to induce IR to better understand the role of cardiac BCAA
      oxidation in cardiac IR. BCAA oxidation, GO, FAO, and glycolysis were measured in
      isolated working hearts from mice fed a low fat diet (LFD) or HFD for 10 wk.
      Insulin stimulation of cardiac GO and inhibition of FAO was blunted in HFD mice,
      resulting in a marked increase in FAO contribution to ATP production compared to
      LFD mice hearts (71.2% vs 37.1%, respectively). Surprisingly, cardiac BCAA
      oxidation rate was reduced in HFD compared to LFD mice (33.5+/-3.4 vs 56.7+/-7.1
      nmol.min-1.g dry wt-1, respectively, p<0.05, n=9/group). In addition, BCAA
      oxidation contributed approximately 1% of the heart's ATP production and as a
      result alterations in BCAA oxidation could not significantly impact either GO or
      FAO rates. However, the decrease in BCAA oxidation was accompanied by increased
      BCAA concentration, and impaired insulin signaling. These results suggest that
      cardiac IR is not due to an increase in BCAA oxidation and subsequent inhibition
      of GO and FAO. Rather, we propose that an inhibition of BCAA oxidation rate
      contributes to IR by leading to increased BCAA concentration, which negatively
      impacts insulin signaling.

PMID- 30106621
TI  - Pre-Exercise Breakfast Ingestion versus Extended Overnight Fasting Increases
      Postprandial Glucose Flux after Exercise in Healthy Men.
AB  - AIMS: To characterize postprandial glucose flux after exercise in the fed versus
      overnight fasted-state and to investigate potential underlying mechanisms.
      METHODS: In a randomized order, twelve men underwent breakfast-rest (BR; 3 h semi
      recumbent), breakfast-exercise (BE; 2 h semi-recumbent before 60-min of cycling
      (50% peak power output) and overnight fasted-exercise (FE; as per BE omitting
      breakfast) trials. An oral glucose tolerance test (OGTT) was completed post
      exercise (post-rest on BR). Dual stable isotope tracers ([U-13C] glucose
      ingestion and [6,6-2H2] glucose infusion) and muscle biopsies were combined to
      assess postprandial plasma glucose kinetics and intramuscular signaling,
      respectively. Plasma intestinal fatty acid binding (I-FABP) concentrations were
      determined as a marker of intestinal damage. RESULTS: Breakfast before exercise
      increased post-exercise plasma glucose disposal rates during the OGTT, from 44
      g*120 min-1 in FE [35 to 53 g*120 min-1] (mean [normalized 95% CI]) to 73 g*120
      min-1 in BE [55 to 90 g*120 min-1; p = 0.01]. This higher plasma glucose disposal
      rate was, however, offset by increased plasma glucose appearance rates
      (principally OGTT-derived), resulting in a glycemic response that did not differ
      between BE and FE (p = 0.11). Plasma I-FABP concentrations during exercise were
      264 pg*mL-1 [196 to 332 pg*mL-1] lower in BE versus FE (p = 0.01). CONCLUSION:
      Breakfast before exercise increases post-exercise postprandial plasma glucose
      disposal, which is offset (primarily) by increased appearance rates of orally
      ingested glucose. Therefore, metabolic responses to fed-state exercise cannot be
      readily inferred from studies conducted in a fasted state.

PMID- 30106623
TI  - Pregnancy stage determines the effect of chronic stress on ovarian progesterone
      synthesis.
AB  - Stress-induced glucocorticoid release is thought to be a primary driver by which
      maternal stress negatively impacts pregnancy outcomes, but the neuroendocrine
      targets mediating these adverse outcomes are less well understood. We
      hypothesized that stress-induced glucocorticoid secretion influences pituitary
      hormone secretion, resulting in altered ovarian progesterone synthesis. Using a
      chronic restraint model of stress in mice, we quantified pituitary hormones,
      steroid hormone production, and expression of ovarian genes that support
      progesterone production at both early- (day 5) and mid-pregnancy (day 10).
      Females subjected to daily restraint had elevated baseline corticosterone during
      both early- and mid-pregnancy. However, lower circulating progesterone was
      observed only during early pregnancy. Lower progesterone production was
      associated with lower expression of steroidogenic enzymes in the ovary of
      restrained females during early pregnancy. There were no stress-related changes
      to luteinizing hormone (LH) or prolactin (PRL). By mid-pregnancy, circulating LH
      decreased regardless of treatment, and this was associated with down-regulation
      of ovarian steroidogenic gene expression. Our results are consistent with a role
      for LH in maintaining steroidogenic enzyme expression in the ovary, but neither
      circulating PRL nor LH were associated with the stress-induced inhibition of
      ovarian progesterone production during early pregnancy. We conclude that chronic
      stress impacts endocrine networks differently not only in pregnant and non
      pregnant mammals, but also in different stages of pregnancy.

PMID- 30106624
TI  - Increases in bioactive lipids accompany early metabolic changes associated with
      beta-cell expansion in response to short-term high fat diet.
AB  - Pancreatic beta-cell expansion is a highly regulated metabolic adaptation to
      increased somatic demands, including obesity and pregnancy; adult beta-cells
      otherwise rarely proliferate. We previously showed that high fat diet (HFD)
      feeding induces mouse beta-cell proliferation in less than one week in the
      absence of insulin resistance. Here we metabolically profiled tissues from a
      short-term HFD beta-cell expansion mouse model to identify pathways and
      metabolite changes associated with beta-cell proliferation. Mice fed HFD vs CD
      showed a 14.3% increase in body weight after 7 days; beta-cell proliferation
      increased 1.75-fold without insulin resistance. Plasma from one-week HFD-fed mice
      induced beta-cell proliferation ex vivo. The plasma, as well as liver, skeletal
      muscle, and bone, were assessed by LC and GC mass-spectrometry for global
      metabolite changes. Of the 1283 metabolites detected, 159 showed significant
      changes (FDR<0.1). The majority of changes were in liver and muscle. Pathway
      enrichment analysis revealed key metabolic changes in steroid synthesis and lipid
      metabolism, including free fatty acids and other bioactive lipids. Other
      important enrichments included changes in the citric acid cycle and 1-carbon
      metabolism pathways implicated in DNA methylation. Although the minority of
      changes were observed in bone and plasma (<20), increased p-cresol sulfate was
      increased >4 fold in plasma (the largest increase in all tissues), and
      pantothenate (vitamin B5) decreased >2-fold. The results suggest that HFD
      mediated beta-cell expansion is associated with complex, global metabolite
      changes. The finding could be a significant insight into Type 2 diabetes
      pathogenesis and potential novel drug targets.

PMID- 30106625
TI  - Listen... and Speak: A Discussion of Weight Bias, its Intersections with
      Homophobia, Racism, and Misogyny, and Their Impacts on Health.
AB  - This article is a version of the Ryley-Jeffs Memorial Lecture, delivered on 8
      June 2018. It discusses weight bias and the intersections with homophobia,
      racism, and misogyny, and how these impact health. While the dominant discourse
      attests that people can lose weight and keep it off, evidence informs us that
      maintenance of weight loss is unlikely. Using a flawed epistemological framework,
      obesity has been declared a disease, and weight bias been perpetuated. Weight
      bias is pervasive, both in the general public and amongst health professionals,
      often using inappropriate tools to assess the impact of weight on health. This
      contributes to overlooking the life circumstances that truly cause morbidity:
      social determinants of health such as income, social connectedness and isolation,
      adverse childhood experiences, and cultural erasure. A variety of tools
      dietitians can use to appropriately assess health risk are provided, along with
      examples of actions that can be taken to reduce weight bias. Dietitians who are
      leading the profession in taking action against weight bias and stigma are
      profiled.

PMID- 30106627
TI  - Reducing weight stigma.

PMID- 30106628
TI  - VISUAL VIGNETTE.

PMID- 30106629
TI  - VISUAL VIGNETTE.

PMID- 30106631
TI  - MULTI-SYSTEM SARCOIDOSIS CAUSING PANHYPOPITUITARISM: RAPID IMPROVEMENT WITH
      CORTICOSTEROID THERAPY.

PMID- 30106630
TI  - A COMBINED OUTPATIENT AND INPATIENT OVERNIGHT WATER DEPRIVATION TEST IS EFFECTIVE
      AND SAFE IN DIAGNOSING PATIENTS WITH POLYURIA-POLYDIPSIA SYNDROME.
AB  - OBJECTIVE: The water deprivation test (WDT) is widely used for the differential
      diagnosis of the polyuria-polydipsia syndrome (PPS). However, it is inconvenient
      and may not always be precise in differentiating partial forms of diabetes
      insipidus (DI) from primary polydipsia (PP). The aim of this study was to
      evaluate the results of a combined outpatient and inpatient overnight WDT
      protocol that included an overnight unsupervised period concerning its
      feasibility and safety. METHODS: We performed a retrospective analysis of
      clinical data and laboratory results of 52 patients with PPS undergoing WDT at a
      single center. RESULTS: PP was the most frequent diagnosis, followed by complete
      central DI (cCDI), partial central DI (pCDI), and nephrogenic DI (NDI). Over 90%
      of the patients showed an expected increase in serum osmolality at the end of the
      dehydration period. There were no reports of complications during the overnight
      deprivation period. Post-dehydration urine osmolality and urine-to-serum
      osmolality ratio significantly differentiated all the groups ( P<.05), except for
      cCDI and NDI, which could be differentiated by basal and post-dehydration
      vasopressin (AVP) levels ( P<.05 for both). Although these measurements were
      useful for differentiating patients according to their allocation groups, results
      from WDT and direct AVP levels may often require a comprehensive diagnostic
      approach, particularly in the challenging groups of PP and pCDI. CONCLUSION: A
      combined outpatient and inpatient overnight WDT protocol is safe and feasible
      when the test is performed with special care at experienced centers. Newer
      diagnostic tools are expected to improve the accuracy of PPS diagnosis.
      ABBREVIATIONS: AQP2 = aquaporin-2; AVP = vasopressin; CDI = central diabetes
      insipidus; cCDI = complete central diabetes insipidus; DDAVP = desmopressin; DI =
      diabetes insipidus; IQR = interquartile range; MRI = magnetic resonance imaging;
      Na+ = sodium; NDI = nephrogenic diabetes insipidus; pCDI = partial central
      diabetes insipidus; PP = primary polydipsia; PPS = polyuria-polydipsia syndrome;
      S_osm = serum osmolality; U_osm = urine osmolality; WDT = water deprivation test.

PMID- 30106632
TI  - Be Aware of the Patient With Benign Follicular Thyroid Lesion Histology and
      Rising Thyroglobulin Level.
AB  - OBJECTIVE: The accurate diagnosis of thyroid follicular/Hurthle cell tumors is
      challenging and a matter of controversy. We present a series of patients in whom
      a misclassification of follicular/Hurthle cell thyroid lesions as benign has led
      to devastating clinical outcomes. METHODS: The Thyroid Cancer Registry of Rabin
      Medical Center was screened for patients with metastatic differentiated thyroid
      carcinoma (DTC) who had been initially diagnosed with benign follicular lesion
      between 1974 and 2015 and treated with hemithyroidectomy. Clinical, pathologic,
      and outcome data were collected from the medical files. Adequate pathology
      specimens, when available, were re-evaluated. RESULTS: Seven patients met the
      inclusion criteria. The original pathologic diagnosis was follicular adenoma in 4
      patients and Hurthle cell adenoma in 3 patients. Five patients had bone
      metastases, of whom one also had lung metastases and one, liver metastases. One
      patient had both cervical and lung metastases, and 1 patient had only meta-static
      neck lymph nodes. Six patients had a final diagnosis of encapsulated follicular
      variant of papillary thyroid carcinoma (EFVPTC), and 1 patient was diagnosed as
      having follicular thyroid cancer metastasis by bone biopsy. In 3 of the patients,
      capsular invasion was detected retrospectively; only 1 patient had evidence of
      vascular invasion. All 7 patients had high levels of thyroglobulin at diagnosis
      of metastatic DTC. CONCLUSION: Misclassification of follicular thyroid lesions as
      benign may lead to progressive disseminated DTC. To minimize the clinical risk of
      misdiagnosis, especially if a thorough evaluation of the specimens by an
      experienced pathologist is unfeasible, we suggest long-term follow-up of serum
      thyroglobulin levels. ABBREVIATIONS: DTC = differentiated thyroid carcinoma;
      EFVPTC = encapsulated follicular variant of papillary thyroid carcinoma; FVPTC =
      follicular variant of papillary thyroid carcinoma; NIFTP = noninvasive follicular
      thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid
      carcinoma.

PMID- 30106633
TI  - VISUAL VIGNETTE.

PMID- 30106634
TI  - VISUAL VIGNETTE.

PMID- 30106635
TI  - Interpretation of Unexpectedly High Levels of Endocrine Tumor Markers.
AB  - OBJECTIVE: Endocrine tumor markers (ETMs) are important and indispensable tools
      in the diagnosis and follow-up of endocrine tumors. Unexpectedly high level of
      ETM (UHLETM) is often encountered in clinical practice. The objectives of this
      article are to discuss the approach to UHLETMs and describe the most common
      UHLETMs. METHODS: Literature review and personal experience with UHLETMs.
      RESULTS: A UHLETM is defined as an ETM level much higher than what an
      endocrinologist would expect based on the patient's clinical information, other
      biochemical test results, and imaging findings. Most UHLETMs are false positive,
      in that they do not indicate the existence or growth of an endocrine tumor. The
      key issue, however, is how to convincingly prove that a UHLETM is false positive.
      The most important question to help resolve UHLETMs is whether the UHLETMs are
      due to false or true results. Some UHLETMs are due to interpretation errors,
      laboratory errors, or spurious test results, while the true levels of the ETMs
      are normal or unchanged from previous results. Other UHLETMs are due to nontumor
      conditions or medications, and the true levels of the ETMs are indeed very high.
      When it is not straightforward to assess whether certain UHLETMs are due to false
      or true results, they may be due to novel conditions. CONCLUSION: UHLETMs provide
      endocrinologists great opportunities to learn the basic biology and measurement
      of ETMs. Unresolved UHLETMs are exciting clinical research opportunities which
      may lead to discovery of new diseases and new mechanisms of measurement
      interference. ABBREVIATIONS: 5-HIAAA = 5-hydroxyindoleacetic acid; 5-HTP = 5
      hydroxytryptophan; CGA = chromogranin A; ETM = endocrine tumor marker; MTC =
      medullary thyroid carcinoma; UHLETM = unexpectedly high level of endocrine tumor
      marker.

PMID- 30106636
TI  - First-Line Trastuzumab Plus an Aromatase Inhibitor, With or Without Pertuzumab,
      in Human Epidermal Growth Factor Receptor 2-Positive and Hormone Receptor
      Positive Metastatic or Locally Advanced Breast Cancer (PERTAIN): A Randomized,
      Open-Label Phase II Trial.
AB  - PURPOSE: To assess pertuzumab plus trastuzumab and an aromatase inhibitor (AI) in
      patients with human epidermal growth factor receptor 2 (HER2)-positive and
      hormone receptor-positive metastatic/locally advanced breast cancer (MBC/LABC).
      PATIENTS AND METHODS: The PERTAIN trial (NCT01491737) is an ongoing randomized,
      open-label, multicenter-80 sites and eight countries-phase II trial. Patients
      have HER2-positive, hormone receptor-positive MBC/LABC and no prior systemic
      therapy with the exception of endocrine. Random assignment was 1:1 to intravenous
      pertuzumab (840 mg loading dose followed by 420 mg every 3 weeks) plus
      trastuzumab (8 mg/kg followed by 6 mg/kg every 3 weeks), and oral anastrozole (1
      mg every day) or letrozole (2.5 mg every day), or trastuzumab and an AI.
      Induction intravenous docetaxel every 3 weeks or paclitaxel every week could be
      administered for 18 to 24 weeks at the investigator's discretion (decided before
      but given after random assignment). Primary end point was progression-free
      survival (PFS). Patients were stratified by whether they received induction
      chemotherapy and their time since adjuvant hormone therapy. RESULTS: One hundred
      twenty-nine patients were randomly assigned per arm (February 2012 to October
      2014; intent-to-treat populations); 75 in one arm and 71 in the other were chosen
      to receive induction chemotherapy. Stratified median PFS was 18.89 months (95%
      CI, 14.09 to 27.66 months) in the pertuzumab plus trastuzumab arm and 15.80
      months (95% CI, 11.04 to 18.56 months) in the trastuzumab arm (stratified hazard
      ratio, 0.65; 95% CI, 0.48 to 0.89; P = .0070). Serious adverse events (AEs) were
      reported for 42 (33.1%) of 127 and 24 (19.4%) of 124 patients in the safety
      populations of the pertuzumab plus trastuzumab and trastuzumab arms,
      respectively. Rates of grade >= 3 AEs were 64 (50.4%) of 127 and 48 (38.7%) of
      124, respectively. There were no deaths as a result of AEs. CONCLUSION: PERTAIN
      met its primary PFS end point. Pertuzumab plus trastuzumab and an AI is effective
      for the treatment of HER2-positive MBC/LABC. The safety profile was consistent
      with previous trials of pertuzumab plus trastuzumab.

PMID- 30106637
TI  - Randomized Trial of Hypofractionated, Dose-Escalated, Intensity-Modulated
      Radiation Therapy (IMRT) Versus Conventionally Fractionated IMRT for Localized
      Prostate Cancer.
AB  - PURPOSE: Hypofractionated radiotherapy delivers larger daily doses of radiation
      and may increase the biologically effective dose delivered to the prostate. We
      conducted a randomized trial testing the hypothesis that dose-escalated,
      moderately hypofractionated intensity-modulated radiation therapy (HIMRT)
      improves prostate cancer control compared with conventionally fractionated IMRT
      (CIMRT) for men with localized prostate cancer. PATIENTS AND METHODS: Men were
      randomly assigned to 75.6 Gy in 1.8-Gy fractions delivered over 8.4 weeks (CIMRT)
      or 72 Gy in 2.4 Gy fractions delivered over 6 weeks (HIMRT, biologically
      equivalent to 85 Gy in 1.8-Gy fractions assuming prostate cancer alpha-to-beta
      ratio of 1.5). Failure was defined as prostate-specific antigen (PSA) failure
      (nadir plus 2 ng/mL) or initiation of salvage therapy. Modified Radiation Therapy
      Oncology Group criteria were used to grade late (>= 90 days after completion of
      radiotherapy) GI and genitourinary toxicity. RESULTS: Most of the 206 men (72%)
      had cT1, Gleason score 6 or 7 (99%), and PSA level <= 10 ng/mL (90%) disease.
      Androgen deprivation therapy was received by 24%. With a median follow-up of 8.5
      years, men treated with HIMRT experienced fewer treatment failures (n = 10) than
      men treated with CIMRT (n = 21; P = .036). The 8-year failure rate was 10.7% (95%
      CI, 5.8% to 19.1%) with HIMRT and 15.4% (95% CI, 9.1% to 25.4%) with CIMRT. There
      was no difference in overall survival ( P = .39). There was a nonsignificant
      increase in late grade 2 or 3 GI toxicity with HIMRT (8-year 5.0% v 12.6%; P =
      .08). However, GI toxicity was only 8.6% when rectal volume receiving 65 Gy of
      HIMRT was <= 15%. Late genitourinary toxicity was similar ( P = .84). There was
      no grade 4 toxicity. CONCLUSION: The results of this randomized trial demonstrate
      superior cancer control for men with localized prostate cancer who receive dose
      escalated moderately hypofractionation radiotherapy while shortening treatment
      duration.

PMID- 30106638
TI  - Tumor Mutation Burden as a Biomarker in Resected Non-Small-Cell Lung Cancer.
AB  - Purpose The survival benefit with adjuvant chemotherapy for patients with
      resected stage II-III non-small-cell lung cancer (NSCLC) is modest. Efforts to
      develop prognostic or predictive biomarkers in these patients have not yielded
      clinically useful tests. We report findings from the Lung Adjuvant Cisplatin
      Evaluation (LACE)-Bio-II study, in which we analyzed next-generation sequencing
      and long-term outcomes data from > 900 patients with early-stage NSCLC treated
      prospectively in adjuvant landmark clinical trials. We used a targeted gene panel
      to assess the prognostic and predictive effect of mutations in individual genes,
      DNA repair pathways, and tumor mutation burden (TMB). Methods A total of 908
      unmatched, formalin-fixed, paraffin-embedded, resected lung cancer tumor
      specimens were sequenced using a targeted panel of 1,538 genes. Stringent
      filtering criteria were applied to exclude germline variants and artifacts
      related to formalin fixation. Disease-free survival, overall survival, and lung
      cancer-specific survival (LCSS) were assessed in Cox models stratified by trial
      and adjusted for treatment, age, sex, performance score, histology, type of
      surgery, and stage. Results Nonsynonymous mutations were identified in 1,515
      genes in 908 tumor samples. High nonsynonymous TMB (> 8 mutations/Mb) was
      prognostic for favorable outcomes (ie, overall survival, disease-free survival,
      and LCSS) in patients with resected NSCLC. LCSS benefit with adjuvant
      chemotherapy was more pronounced in patients with low nonsynonymous TMBs (<= 4
      mutations/Mb). Presence of mutations in DNA repair pathways, tumor-infiltrating
      lymphocytes, TP53 alteration subtype, and intratumor heterogeneity was neither
      prognostic nor predictive. Statistically significant effect of mutations in
      individual genes was difficult to determine due to high false-discovery rates.
      Conclusion High nonsynonymous TMB was associated with a better prognosis in
      patients with resected NSCLC. In addition, the benefit of adjuvant chemotherapy
      on LCSS was more pronounced in patients with low nonsynonymous TMBs. Studies are
      warranted to confirm these findings.

PMID- 30106640
TI  - Novel Transabdominal Preperitoneal Hernioplasty Technique for Recurrent Inguinal
      Hernia: Overlapping of Whole Posterior Wall with Newly Added Mesh and Pre
      existing Mesh by Closing Hernia Defect.
AB  - PURPOSE: In some patients with recurrent inguinal hernias who have undergone
      previous laparoscopic herniorrhaphy, dissecting the entire posterior wall is
      difficult due to mesh adhesion. We applied a novel transabdominal preperitoneal
      (TAPP) hernioplasty technique that involves closing of the hernia defect and
      implantation of a newly added mesh while preserving the pre-existing mesh for
      inguinal hernia recurrence after laparoscopic herniorrhaphy. This study was
      performed to evaluate this novel technique for treatment of recurrent inguinal
      hernias. METHODS: We evaluated 24 adult patients (23 male, 1 female; mean age,
      55.8 +/- 14.0 years; range, 26-77 years) with recurring inguinal hernias. A
      modified TAPP (mTAPP) procedure involving closing of the defect and implantation
      of an 8 * 6-cm2 newly added mesh was performed. The new technique covered the
      whole posterior wall with pre-existing mesh. RESULTS: Among the 24 patients,
      there were 12 direct hernias and 12 indirect hernias. The mean postoperative pain
      scores after 1 week were 2.5 and 2.0 in patients with direct and indirect
      hernias, respectively, and the mean duration until return to normal activities
      was 8.5 and 7.5 days in patients with direct and indirect hernias, respectively.
      The mean follow-up period was 21.0 +/- 17.0 (range, 2-56) months. No chronic
      inguinodynia or rerecurrence was observed. CONCLUSIONS: In this novel mTAPP
      procedure for recurring inguinal hernias, closing sutures prevented mesh
      migration, and complete posterior wall overlap was possible using the pre
      existing mesh and newly added mesh. The mTAPP procedure was an effective
      operation with few recurrences and complications.

PMID- 30106639
TI  - Serum Biomarker Signature-Based Liquid Biopsy for Diagnosis of Early-Stage
      Pancreatic Cancer.
AB  - PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5
      year survival of < 10% because of diffuse symptoms leading to late-stage
      diagnosis. That survival could increase significantly if localized tumors could
      be detected early. Therefore, we used multiparametric analysis of blood samples
      to obtain a novel biomarker signature of early-stage PDAC. The signature was
      derived from a large patient cohort, including patients with well-defined early
      stage (I and II) PDAC. This biomarker signature was validated subsequently in an
      independent patient cohort. PATIENTS AND METHODS: The biomarker signature was
      derived from a case-control study, using a Scandinavian cohort, consisting of 16
      patients with stage I, 132 patients with stage II, 65 patients with stage III,
      and 230 patients with stage IV PDAC, and 888 controls. This signature was
      validated subsequently in an independent case-control cohort in the United States
      with 15 patients with stage I, 75 patients with stage II, 15 patients with stage
      III, and 38 patients with stage IV PDAC, and 219 controls. An antibody microarray
      platform was used to identify the serum biomarker signature associated with early
      stage PDAC. RESULTS: Using the Scandinavian case-control study, a biomarker
      signature was created, discriminating samples derived from patients with stage I
      and II from those from controls with a receiver operating characteristic area
      under the curve value of 0.96. This signature, consisting of 29 biomarkers, was
      then validated in an independent case-control study in the United States. The
      biomarker signature could discriminate patients with stage I and II PDAC from
      controls in this independent patient cohort with a receiver operating
      characteristic area under the curve value of 0.96. CONCLUSION: This serum
      biomarker signature might represent a tenable approach to detecting early-stage,
      localized PDAC if these findings are supported by a prospective validation study.

PMID- 30106641
TI  - Force Resistance Training in Hand Grasp and Arm Therapy: Feasibility of a Low
      Cost Videogame Controller.
AB  - OBJECTIVE: To design and evaluate a low-cost gaming station that supports force
      resistance training in pediatric arm/hand grasp therapies through mainstream
      videogame play. METHODS: The gaming station was developed through an iterative
      participatory design process and includes a force feedback game controller
      (Novint Falcon), custom grips, arm/wrist supports, and software to interface with
      mainstream games and manage difficulty settings in the controller. The station
      was tested for usability and feasibility with six therapists and six children
      with cerebral palsy, 7-16 years of age, attending weekly therapy sessions over 12
      weeks. Pre- and post-assessments of perceived performance and satisfaction on
      self-identified goals were measured on the Canadian Occupational Performance
      Measure (COPM). RESULTS: The gaming station was considered highly usable by
      therapists with a score of 76.7 (standard deviation [SD] = 6.1) on the System
      Usability Scale. Overall, children enjoyed the games, achieved high repetition
      rates for wrist extensions and arm movements, and all made clinically significant
      progress on therapy goals. Increases of 3.13 (SD = 1.69) on the performance scale
      and 2.97 (SD = 0.98) on the satisfaction scale were reported on the COPM.
      Conclusiion: In-clinic force resistance training for development of upper limb
      functional capacities is feasible using low-cost video game components adapted to
      therapy through a participatory design process.

PMID- 30106642
TI  - Developing Digital Intervention Games for Mental Disorders: A Review.
AB  - There is limited research on mental health interventions delivered in a digital
      game format and even less to guide developers on how to develop such games. This
      review focuses on understanding how to develop therapeutic digital games based
      primarily on mental health intervention games that have been empirically tested.
      The review was generated through database searches and backward search techniques
      for digital game-based interventions for specific mental disorders. We evaluated
      digital games that were based on validated psychological treatments. We located
      24 studies and 18 games that met our search criteria. These games and their
      outcomes have been summarized. This review showed that these types of games have
      the potential to make an impact on mental health concerns but that there are
      currently few digital games available for the treatment or prevention of mental
      disorders. In addition, guidelines for digital mental health intervention game
      development have been presented. The consolidation of guidelines addressing
      multiple game development factors (e.g., time, cost, engagement) may help those
      interested in developing new therapeutic games that target a greater variety of
      disorders, thereby expanding access to larger populations.

PMID- 30106644
TI  - 21st Century Citizen Pharma: The FDA & Patient-Focused Product Development.
AB  - Perpetual debate regarding the delicate balance between access and innovation and
      the protection of the public health and safety dominate discussions of the United
      States Food and Drug Administration ("FDA"). Established chiefly as a command and
      control federal administrative agency, iterative changes in legislation have
      shaped the FDA's activity in drug, biologic, and medical device regulation over
      the course of the last one hundred plus years. The most recent fundamental
      reframing of the agency's authority and directive presented itself in the 21st
      Century Cures Act, reflecting an important role for patient perspectives in the
      regulatory process. This Article explores recent developments in patient-focused
      product development efforts at the FDA and offers modest insights on the
      increasing role of patients, and patient advocacy groups, in agency decision
      making. The Article terms this era "21st century citizen pharma."

PMID- 30106643
TI  - Executive Functioning of Older Adults Correlates with Performance of Touchscreen
      App-Based Puzzles.
AB  - BACKGROUND: The use of touchscreen tablets has become common in healthcare. This
      technology has the potential to be used as a motivational tool for cognitive
      training. Age-related decline in executive functioning (EF) and dexterity may
      lead to poor performance using tablet applications (apps), but the impact on
      performance of app-based puzzles has not been studied. OBJECTIVES: (1) To
      characterize and compare the experience performance of playing tablet apps of
      older and younger adults, (2) To determine if EF and dexterity contribute to
      performance of app-based puzzles. MATERIALS AND METHODS: We performed a cross
      sectional study of community-dwelling healthy older (n = 35) and younger adults
      (n = 34). EF was measured by the Trail Making Test (part B) (TMT-B) and the
      Weekly Calendar Planning Activity. Dexterity was assessed using the Nine-Hole Peg
      Test. Participants played three unfamiliar app-based puzzles requiring EF and
      filled out the short feedback questionnaire. RESULTS: All participants succeeded
      in playing the apps and reported enjoyment, however, older adults perceived less
      success and control. Significant differences in EF, dexterity, and performance
      were found between groups. EF of older adults (TMT-B) accounted for 17.7%-36.8%
      (P < 0.05) of the total variance of performance. CONCLUSION: These findings have
      implications for the use of tablet apps for older adults. Longer instruction and
      training periods may be required for training EF among older adults.

PMID- 30106645
TI  - Fast-Forward to the Frightening Future: How the 21st Century Cures Act
      Accelerates Technological Innovation...at Unknown Risk to Us All.

PMID- 30106646
TI  - 21st Century Cures Act and Medical Device Regulation Departure from Principles or
      Catching the Wave.

PMID- 30106647
TI  - Real-World Evidence in the Real World: Beyond the FDA.
AB  - The 21st Century Cures Act ("Cures Act") 1 relies on the concept of real-world
      evidence ("RWE") 2 to improve the Food and Drug Administration ("FDA") approval
      process. This has amplified interest and furthered momentum in applying RWE more
      broadly, beyond FDA regulation. In this article, we discuss the understandable
      appeal of RWE's pragmatic application and its many potential benefits. But we
      also caution that claims about RWE's wide-ranging, ameliorative impact on the
      health care system are likely overstated. The real world of RWE is messy and
      uncertain. Successfully incorporating RWE into regular health care system
      decision-making, beyond the FDA, faces considerable obstacles and limitations. We
      review the reasons to be wary about RWE as a game-changer. These concerns
      including data reliability, insufficient incentives for stakeholders to generate
      and engage with high-quality RWE, and lack of comprehensive regulatory oversight.
      In addition, the push for RWE may impact the enforcement of the health care fraud
      and abuse laws, perhaps not in necessarily positive ways. Increased reliance on
      RWE may have significant implications for off-label fraud enforcement, further
      conflating the distinction between claims that are false for reimbursement rather
      than for scientific purposes.

PMID- 30106648
TI  - The Challenge of Regulating Clinical Decision Support Software After 21st Century
      Cures.

PMID- 30106649
TI  - Real-World Data Analytics Fit for Regulatory Decision-Making.
AB  - Healthcare database analyses (claims, electronic health records) have been
      identified by various regulatory initiatives, including the 21st Century Cures
      Act and Prescription Drug User Fee Act ("PDUFA"), as useful supplements to
      randomized clinical trials to generate evidence on the effectiveness, harm, and
      value of medical products in routine care. Specific applications include
      accelerated drug approval pathways and secondary indications for approved medical
      products. Such real-world data ("RWD") analyses reflect how medical products
      impact health outside a highly controlled research environment. A constant stream
      of data from the routine operation of modern healthcare systems that can be
      analyzed in rapid cycles enables incremental evidence development for regulatory
      decision-making. Key evidentiary needs by regulators include 1) monitoring of
      medication performance in routine care, including the effectiveness, safety and
      value; 2) identifying new patient strata in which a drug may have added value or
      unacceptable harms; and 3) monitoring targeted utilization. Four broad
      requirements have been proposed to enable successful regulatory decision-making
      based on healthcare database analyses (collectively, "MVET"): Meaningful evidence
      that provides relevant and context-informed evidence sufficient for
      interpretation, drawing conclusions, and making decisions; valid evidence that
      meets scientific and technical quality standards to allow causal interpretations;
      expedited evidence that provides incremental evidence that is synchronized with
      the decision-making process; and transparent evidence that is audible,
      reproducible, robust, and ultimately trusted by decision-makers. Evidence
      generation systems that satisfy MVET requirements to a high degree will
      contribute to effective regulatory decision-making. Rapid-cycle analytics of
      healthcare databases is maturing at a time when regulatory overhaul increasingly
      demands such evidence. Governance, regulations, and data quality are catching up
      as the utility of this resource is demonstrated in multiple contexts.

PMID- 30106650
TI  - 21st Century Cures for the Opioid Crisis: Promise, Impact, and Missed
      Opportunities.

PMID- 30106651
TI  - Practice-Based Research Networks and the Mandate for Real-World Evidence.
AB  - The 21st Century Cures Act encourages the Food and Drug Administration to
      consider "real-world evidence" in its regulation of the safety and efficacy of
      drugs and devices. Many have interpreted this mandate to focus on non-randomized
      observational research. However, we suggest that regulatory science must also
      move from rarefied academic hospitals to community-based settings, where the vast
      majority of patients in fact receive care in the fragmented U.S. healthcare
      system. This move is especially important if innovations are to reach, and be
      validated in, more diverse populations. A solution can be found in the 183
      Practiced-Based Research Networks ("PBRN"), i.e., groups of primary care
      clinicians and practices in all 50 states working to improve clinical care and
      translate research findings into practice. This symposium contribution seeks to
      (1) describe some of the common shortcomings of clinical trials, (2) explore the
      opportunities and challenges posed by use of real-world evidence as a basis for
      drug and device regulation, (3) briefly describe the history and evolution of
      PBRNs, and (4) articulate the challenges and opportunities for using PBRNs to
      fulfill the 21st Century Cures Act mandate for real-world evidence.

PMID- 30106652
TI  - How the 21st Century Cures Act Can Mitigate the Ever Growing Problem of Mass
      Incarceration.

PMID- 30106654
TI  - Preface: The 21st Century Cures Act-A Cure for the 21st Century?

PMID- 30106653
TI  - A RAT by Another Name: 21st Century Cures Act and Stem Cell Therapies.

PMID- 30106655
TI  - The 21st Century Cures Potpourri: Was It Worth the Price?

PMID- 30106656
TI  - Massachusetts Approves Mass. Eye & Ear and Partners HealthCare Merger.

PMID- 30106657
TI  - The Evolution of Federal Regulation of Human Drugs in the United States: An
      Historical Essay.

PMID- 30106658
TI  - The Growing Importance of Mental Health Parity.

PMID- 30106659
TI  - Off-Label Marketing's Audiences: The 21st Century Cures Act and the Relaxation of
      Standards for Evidence-Based Therapeutic and Cost-Comparative Claims.

PMID- 30106660
TI  - New and Improved? 21st Century Cures Act Revisions to Certificates of
      Confidentiality.
AB  - Certificates of Confidentiality ("Certificates") are a federal legal tool
      designed to protect sensitive, identifiable research data from compelled
      disclosure. Congress first authorized their use in 1970 to facilitate research on
      illegal drug use. The scope of their use was later expanded to cover mental
      health research and then again to apply broadly to identifiable, sensitive
      research data, regardless of topic. Certificates can be critical to enabling
      conduct of essential research on sensitive topics, such as effective
      interventions to curb the opioid epidemic or reduce HIV transmission among
      minority youth. Nevertheless, there have been criticisms about Certificates and
      their use on several grounds. For example, researchers and institutional review
      boards ("IRBs") may lack sufficient knowledge about them and, therefore, may not
      consider using them in studies for which they would be appropriate. In contrast
      to other protections, such as Department of Justice Privacy Certificates,
      Certificate protections were not automatically extended to these studies, but
      instead required an application. In addition, the concept of identifiable data
      had not kept up with technological changes that may allow for reidentification of
      data previously considered unidentifiable. Although a researcher who obtained a
      Certificate could use it to resist a legal demand for identifiable data, little
      was known about the actual effectiveness of the protection provided. The 21st
      Century Cures Act substantially revises the Certificates authorizing statute, and
      many of the changes are directly responsive to the criticisms that have been
      raised. Significantly, the Secretary of the Department of Health and Human
      Services ("HHS") must issue Certificate protection to federally funded research
      involving identifiable, sensitive research data, and the National Institutes of
      Health ("NIH") will automatically include such protections to research it funds.
      Non-federally funded researchers can continue to apply for Certificate
      protection. The definition of identifiable has been expanded to include data "for
      which there is at least a very small risk" of identification. Certificates will
      now not only protect against compelled disclosure, but also render protected data
      inadmissible in legal proceedings without participant consent. In addition,
      voluntary disclosure is no longer authorized, but there is now a broad exception
      for disclosure as required by federal, state, and local laws. In this paper,
      based on our previous research on Certificates, we critically evaluate the 21st
      Century Cures Act's Certificates revisions and their positive and negative impact
      on the dual goals of facilitating important, sensitive research while maximally
      protecting individual research participants.

PMID- 30106661
TI  - Expansion of the Priority Review Voucher Program Under the 21st Century Cures
      Act: Implications for Innovation and Public Health.

PMID- 30106662
TI  - Veterinary Medical Students' Motivations for Exercise.
AB  - The Centers for Disease Control (CDC) declares exercise to be one of the most
      important activities one can do to improve health. The benefits of exercise are
      well documented and include both physiologic and psychological health. Given the
      current landscape of wellness issues in veterinary medical education, it is
      necessary that students engage in exercise activities to manage stress and
      increase overall health. Therefore, to develop targeted interventions with the
      greatest likelihood for success, it is first necessary to understand what
      motivates veterinary medical students to exercise given their unique situational
      and environmental factors. This study is the first to explore this issue
      systematically in veterinary medical education, thus it is the authors' hope that
      the findings from this research will help identify exercise-related wellness
      interventions that could be implemented in veterinary medical schools.

PMID- 30106663
TI  - Changes and Transitions at the JVME.

PMID- 30106664
TI  - Social Support Seeking on Social Media Among Chinese Gay Men Living with
      HIV/AIDS: The Role of Perceived Threat.
AB  - BACKGROUND: Due to a double stigma against HIV/AIDS and homosexuality, gay men
      living with HIV/AIDS (GMLHA) have used social media to exchange social support.
      The current study aims to examine the influence of perceived threat on seeking
      social support on social media among Chinese GMLHA. METHODS: First, Weibo posts
      from 133 GMLHA were content analyzed to identify the perceived severity of HIV
      infection and perceived severity of stigma, as well as their social support
      seeking on Weibo. Then, a 2 * 2 (perceived severity of HIV infection [present,
      absent] * perceived severity of stigma [present, absent]) between-subject
      multivariate analysis of variance with social support seeking as the dependent
      variable was performed. RESULTS: Perceived severity of HIV infection and
      perceived severity of stigma had main effects on different kinds of social
      support seeking. Moreover, GMLHA who expressed both perceived severity of HIV
      infection and perceived severity of stigma on Weibo posted the greatest number of
      emotional support-seeking messages. CONCLUSIONS: This study revealed that
      perceived threat was one of the motivations of GMLHA to seek online social
      support.

PMID- 30106665
TI  - Studies of Impending Oligonucleotide Therapeutics in Simulated Biofluids.
AB  - Synthetic oligonucleotides, their complexes and conjugates with other
      biomolecules represent valuable research tools and therapeutic agents. In spite
      of growing applications in basic research and clinical science, only few studies
      have addressed the issue of such compounds' stability in biological media.
      Herein, we studied the stability of two therapeutically relevant oligonucleotide
      probes in simulated biofluids; the 21 nucleotide-long DNA/locked nucleic acid
      oligonucleotide ON targeted toward cancer-associated BRAF V600E mutation, and a
      longer DNA analog (TTC) originating from BRAF gene. We found that stability of
      peptide-oligonucleotide conjugates (POCs) in human serum (HS) was superior
      compared with the naked or complexed 21mer oligonucleotide, whereas stability of
      POCs in simulated gastric juice (GJ) was dependent on the peptide sequence.
      Addition of pepstatin A in general increased the stability of oligonucleotides
      after 24 h digestion in HS and simulated GJ. Similarly, complexation with optimal
      amounts of histone proteins was found to rescue oligonucleotide stability after
      24 h digestion in hydrochloric acid.

PMID- 30106666
TI  - Expression of Autophagy Signaling Molecules in the Outer Membranes of Chronic
      Subdural Hematomas.
AB  - Chronic subdural hematoma (CSDH) is fundamentally treatable, although it
      sometimes recurs. We observed, however, several cases of spontaneous resolution
      of CSDH outer membranes, even in a trabecular type of CSDH, after a trepanation
      surgical procedure. In this study, we examined the expression of molecules of the
      autophagy signaling pathway in CSDH outer membranes. Eight patients whose outer
      membranes were obtained successfully during trepanation were included in this
      study. By Western blot analysis, we examined the expression of mammalian target
      of rapamycin (mTOR); GbetaL; UNC-51-like kinase-1 (ULK1); Beclin-1; autophagy
      related genes (Atg) 3, 5, 7, 12, 13, and 16L1beta,alpha; the autophagy marker
      Light Chain3A/B (LC3A/B); and beta-actin, which constitute the autophagy
      signaling pathway. The expression levels of Beclin-1, Atg12, and LC3A/B were also
      examined by immunohistochemistry. Almost all of these molecules could be detected
      in all samples. Beclin-1, Atg12, and LC3A/B were found to be localized in the
      endothelial cells of vessels and fibroblasts in CSDH. We detected molecules of
      the autophagy signaling pathway in CSDH outer membranes. Autophagy contributes to
      the tissue homeostatic process, maintaining cellular integrity by clearing
      debris. Our data suggest that autophagy might play an important role in the
      spontaneous resolution of CSDH. Therefore, these molecules may be novel
      therapeutic targets for the treatment of those with CSDH.

PMID- 30106667
TI  - Do Perineuronal Net Elements Contribute to Pathophysiology of Spinal Muscular
      Atrophy? In Vitro and Transcriptomics Insights.
AB  - Spinal muscular atrophy (SMA) is one of the most common childhood onset
      neurodegenerative disorders in global health whereby novel biomarkers and
      therapeutic targets are sorely needed. SMA is an autosomal recessive genetic
      disorder resulting in degeneration of alpha-motor neurons in the brain stem and
      spinal cord that leads to mortality in infants worldwide. In majority of the
      patients, SMA is caused by homozygous deletion of the SMN1 gene. The clinical
      spectrum of the SMA displays, however, large person-to-person variations where
      the underlying mechanisms are poorly understood. We report in this study
      transcriptomics insights gleaned from patients with the severe type I (GM03813
      and GM09677) and the mild type III. Pathway enrichment and functional analysis
      showed that especially extracellular matrix (ECM), synapse organization, and ECM
      receptor interaction pathways were affected. Among the neural ECM components,
      hyaluronan and proteoglycan link protein (HAPLN1), which is a key triggering
      molecule of the perineuronal net (PNN), was significantly downregulated in type I
      fibroblasts compared to type III. PNN is a specialized form of neural ECM around
      the neuronal cell bodies and dendrites in the central nervous system. In
      addition, we evaluated the PNN expression in vitro in a model established by SMN
      silencing in the PC12 rat pheochromocytoma cell line which can be differentiated
      into neurons with nerve growth factor treatment. In this neuronal in vitro model,
      we found that HAPLN1 showed a significant 50% decrease. Our results describe the
      association between PNN elements, especially HAPLN1, and SMA pathophysiology for
      the first time. These observations collectively inform future translational
      research on SMA for discovery of novel molecular targets for diagnostics and
      precision medicine innovation.

PMID- 30106668
TI  - A Novel Francisella-Like Endosymbiont in Haemaphysalis longicornis and Hyalomma
      asiaticum, China.
AB  - Francisella tularensis causes a highly infectious zoonotic disease tularemia.
      Both Haemaphysalis longicornis and Hyalomma asiaticum are widely distributed in
      China, but the presence of Francisella and Francisella-like endosymbionts (FLEs)
      in the two tick species is poorly understood. Therefore, a total of 627 H.
      longicornis (471 adults and 156 nymphs) and 88 Hy. asiaticum ticks (adults) were
      collected, of which 88 were from Bole of Xinjiang, 236 from Liaoyang, and 176
      from Shenyang of Liaoning, and 215 from Wuhan of Hubei. Notably, five H.
      longicornis pools from Liaoyang of Liaoning province might have harbored F.
      tularensis, showing a minimum prevalence of 2.12% (5/236). This study should
      alert the health department and veterinarians working within the region to
      prevent and control the emergence of tularemia. After the screening of 16S rRNA
      and tul4 genes, the results revealed that FLEs were detected in Hy. asiaticum
      ticks in Bole and in H. longicornis ticks in Liaoyang and Shenyang. Their
      infection rate was 100% (88/88), 3.39% (8/236 is a minimum), and 8.52% (15/176),
      respectively. Phylogenetic analyses indicated that the sequence named bole in Hy.
      Asiaticum from Bole, the sequence named liaoyang1 in H. longicornis from
      Liaoyang, and the sequence named shanyang1 in H. longicornis from Shenyang shared
      consistent 16S rRNA sequence, and the difference between Chinese FLEs and the
      known FLEs was obvious. These findings suggest that this FLE species might be a
      potentially novel FLE circulating in H. longicornis and Hy. asiaticum from China.

PMID- 30106669
TI  - Exciting History of Tip60 and Its Companions in Carcinogenesis Across the
      Heterochromatin Landscapes.

PMID- 30106670
TI  - Infectious Disease in Contact Sports.
AB  - CONTEXT: Infections are common in contact sports. This review aims to describe
      the epidemiology, presenting signs and symptoms, treatment guidelines, and
      regulations for several common infections seen in contact sport athletes. The
      conditions discussed include bacterial skin infections, herpes simplex virus,
      molluscum contagiosum, common warts, tinea, scabies, head lice, conjunctivitis,
      human immunodeficiency virus, hepatitis C virus, and vaccine-preventable
      illnesses. EVIDENCE ACQUISITION: Searches were performed across PubMed and
      MEDLINE research databases. In addition, general internet search engine results
      and reviews of reference lists of relevant papers were used to identify
      additional sources of evidence. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE:
      Level 4. RESULTS: The most common infections seen in contact sport athletes
      include bacterial skin infections, herpes simplex virus, molluscum contagiosum,
      common warts, tinea, scabies, head lice, conjunctivitis, and vaccine-preventable
      illnesses. Other infections, including human immunodeficiency virus and hepatitis
      C, are uncommon but potentially life threatening. CONCLUSION: Infections are
      common in contact sport athletes. The provider who cares for these athletes
      should be aware of the most common infections and their appropriate management.
      Early diagnosis and appropriate clinical management are important for treating
      the infected athlete, minimizing risk of transmission, minimizing time lost from
      competition, and preventing large outbreaks.

PMID- 30106671
TI  - Asymmetry in Synergistic Interaction between Wheat streak mosaic virus and
      Triticum mosaic virus in Wheat.
AB  - Wheat streak mosaic virus (WSMV) and Triticum mosaic virus (TriMV), distinct
      members in the family Potyviridae, are economically important wheat-infecting
      viruses in the Great Plains region. Previously, we reported that co-infection of
      wheat by WSMV and TriMV cause disease synergism with increased concentration of
      both viruses. The mechanisms of synergistic interaction between WSMV and TriMV
      and the effects of prior infection of wheat by either of these 'synergistically
      interacting partner' (SIP) viruses on the establishment of local and systemic
      infection by the other SIP virus are not known. In this study, using fluorescent
      protein-tagged viruses, we found that prior infection of wheat by WSMV or TriMV
      negatively affected the onset and size of local foci elicited by subsequent SIP
      virus infection compared to those in buffer-inoculated wheat. These data revealed
      that prior infection of wheat by a SIP virus has no measurable advantage for
      another SIP virus on the initiation of infection and cell-to-cell movement. In
      TriMV-infected wheat, WSMV exhibited accelerated long-distance movement and
      increased accumulation of genomic RNAs compared to those in buffer-inoculated
      wheat, indicating that TriMV-encoded proteins complemented WSMV for efficient
      systemic infection. In contrast, TriMV displayed delayed systemic infection in
      WSMV-infected wheat with fewer genomic RNA copies in early stages of infection
      compared to those in buffer-inoculated wheat. However, during late stages of
      infection, TriMV accumulation in WSMV-infected wheat increased rapidly with
      accelerated long-distance movement compared to those in buffer-inoculated wheat.
      Taken together, these data suggest that interactions between synergistically
      interacting WSMV and TriMV are asymmetrical; thus, successful establishment of
      synergistic interaction between unrelated viruses will depend on the order of
      infection of plants by SIP viruses.  .

PMID- 30106673
TI  - A High Definition Non-invasive Neuromuscular Electrical Stimulation System for
      Cortical Control of Combinatorial Rotary Hand Movements in a Human with
      Tetraplegia.
AB  - OBJECTIVE: Paralysis resulting from spinal cord injury (SCI) can have a
      devastating effect on multiple arm and hand motor functions. Rotary hand
      movements, such as supination and pronation, are commonly impaired by upper
      extremity paralysis, and are essential for many activities of daily living. In
      this proof-of-concept study, we utilize a neural bypass system (NBS) to decode
      motor intention from motor cortex to control combinatorial rotary hand movements
      elicited through stimulation of the arm muscles, effectively bypassing the SCI of
      the study participant. We describe the NBS system architecture and design that
      enabled this functionality. METHODS: The NBS consists of three main functional
      components: 1) implanted intracortical microelectrode array, 2) neural data
      processing using a computer, and, 3) a non-invasive neuromuscular electrical
      stimulation (NMES) system. RESULTS: We address previous limitations of the NBS,
      and confirm the enhanced capability of the NBS to enable, in real-time,
      combinatorial hand rotary motor functions during a functionally relevant object
      manipulation task. CONCLUSION: This enhanced capability was enabled by accurate
      decoding of multiple movement intentions from the participant's motor cortex,
      interleaving NMES patterns to combine hand movements, and dynamically switching
      between NMES patterns to adjust for hand position changes during movement.
      SIGNIFICANCE: These results have implications for enabling complex rotary hand
      functions in sequence with other functionally relevant movements for patients
      suffering from SCI, stroke, and other sensorimotor dysfunctions.

PMID- 30106674
TI  - A Generic Multi-Projection-Center Model and Calibration Method for Light Field
      Cameras.
AB  - Light field cameras can capture both spatial and angular information of light
      rays, enabling 3D reconstruction by a single exposure. The geometry of 3D
      reconstruction is affected by intrinsic parameters of a light field camera
      significantly. In the paper, we propose a multi-projection-center (MPC) model
      with 6 intrinsic parameters to characterize light field cameras based on
      traditional two-parallel-plane (TPP) representation. The MPC model can generally
      parameterize light field in different imaging formations, including conventional
      and focused light field cameras. By the constraints of 4D ray and 3D geometry, a
      3D projective transformation is deduced to describe the relationship between
      geometric structure and the MPC coordinates. Based on the MPC model and
      projective transformation, we propose a calibration algorithm to verify our light
      field camera model. Our calibration method includes a close-form solution and a
      non-linear optimization by minimizing re-projection errors. Experimental results
      on both simulated and real scene data have verified the performance of our
      algorithm.

PMID- 30106675
TI  - Sensitivity and Specificity Estimation using Patient-Specific Microwave Imaging
      in Diverse Experimental Breast Phantoms.
AB  - Many new clinical investigations of microwave breast imaging have been published
      in recent years. Trials with over one hundred participants have indicated the
      potential of microwave imaging to detect breast cancer, with particularly
      encouraging sensitivity results reported from women with dense breasts. The next
      phase of clinical trials will involve larger and more diverse populations,
      including women with no breast abnormalities or benign breast diseases. These
      trials will need to address clinical efficacy in terms of sensitivity and
      specificity. A number of challenges exist when using microwave imaging with broad
      populations: 1) addressing the substantial variance in breast composition
      observed in the population; and 2) achieving high specificity given differences
      between individuals. This work analyses these challenges using a diverse phantom
      set which models the variance in breast composition and tumour shape and size
      seen in the population. The data show that the sensitivity of microwave breast
      imaging in breasts of differing density can suffer if patient-specific
      beamforming is not used. Moreover, the results suggest that achieving high
      specificity in dense breasts may be difficult, but that patient-specific
      beamforming does not adversely affect the expected specificity. In summary, this
      work finds that patientspecific beamforming has a tangible impact on expected
      sensitivity in experimental cases and that achieving high specificity in dense
      breasts may be challenging.

PMID- 30106676
TI  - KerNL: Kernel-based NonLinear Approach to Parallel MRI Reconstruction.
AB  - The conventional calibration-based parallel imaging method assumes a linear
      relationship between the acquired multi-channel k-space data and the unacquired
      missing data, where the linear coefficients are estimated using some auto
      calibration data. In this work, we first analyze the model errors in the
      conventional calibration-based methods and demonstrate the nonlinear
      relationship. Then a much more general nonlinear framework is proposed for auto
      calibrated parallel imaging. In this framework, kernel tricks are employed to
      represent the general nonlinear relationship between acquired and unacquired k
      space data without increasing the computational complexity. Identification of the
      nonlinear relationship is still performed by solving linear equations.
      Experimental results demonstrate that the proposed method can achieve
      reconstruction quality superior to GRAPPA and NL-GRAPPA at high net reduction
      factors.

PMID- 30106677
TI  - A Semi-Explicit Surface Tracking Mechanism for Multi-Phase Immiscible Liquids.
AB  - We introduce a new method to efficiently track complex interfaces among multi
      phase immiscible fluids. Unlike existing techniques, we use a mesh-based
      representation for global liquid surfaces, while selectively modeling some local
      surficial regions with regional level sets (RLS) to handle complex geometry that
      is difficult to resolve with explicit topology operations. Such a semi-explicit
      surface mechanism can preserve volume, fine features and foam-like thin films
      under a relatively low computational expenditure. Our method processes the
      surface evolution by sampling the fluid domain onto a spectrally refined grid
      (SRG) and performs efficient grid scanning, generalized interpolations and
      topology operations on the basis of this grid structure. For the RLS surface
      part, we propose an accurate advection scheme targeted at SRG. For the explicit
      mesh part, we develop a fast grid scanning technique to voxelize the meshes and
      introduce novel strategies to detect grid regions that contain inconsistent mesh
      components. A robust algorithm is proposed to construct consistent local meshes
      to resolve mesh penetrations, and handle the coupling between explicit mesh and
      RLS surficial regions. We also provide further improvement on handling
      complicated topological variations, as well as strategies for remeshing mesh/RLS
      interconversions.

PMID- 30106678
TI  - A Computational Model of Thalamocortical Dysrhythmia in People With Tinnitus.
AB  - Tinnitus is a problem that affects a diverse range of people. One common trait
      amongst people with tinnitus is the presence of hearing loss, which is apparent
      in over 90% of the cohort. It is postulated that the remainder of people with
      tinnitus have hidden hearing loss in the form of cochlear synaptopathy. The loss
      of hearing sensation is thought to cause a reduction in the bottom-up excitatory
      signals of the auditory pathway leading to a change in the frequency of
      thalamocortical oscillations known as thalamocortical dysrhythmia (TCD). The
      downward shift in oscillatory behavior, characteristic of TCD, has been recorded
      experimentally but the underlying mechanisms responsible for TCD in tinnitus
      subjects cannot be directly observed. This paper investigates these underlying
      mechanisms by creating a biologically faithful model of the auditory periphery
      and thalamocortical network, called the central auditory processing (CAP) model.
      The proposed model replicates tinnitus related activity in the presence of
      hearing loss and hidden hearing loss in the form of cochlear synaptopathy. The
      results of this paper show that, both the bottom-up and top-down changes are
      required in the auditory system for tinnitus related hyperactivity to coexist
      with TCD, contrary to the theoretical model for TCD. The CAP model provides a
      novel modeling approach to account for tinnitus related activity with and without
      hearing loss. Moreover, the results provide additional clarity to the
      understanding of TCD and tinnitus and provide direction for future approaches to
      treating tinnitus.

PMID- 30106679
TI  - Spatio-Spectral Representation Learning for Electroencephalographic Gait-Pattern
      Classification.
AB  - The brain plays a pivotal role in locomotion by coordinating muscles through
      interconnections that get established by the peripheral nervous system. To date,
      many attempts have been made to reveal the underlying mechanisms of humans' gait.
      However, decoding cortical processes associated with different walking conditions
      using EEG signals for gait-pattern classification is a less-explored research
      area. In this paper, we design an EEG-based experiment with four walking
      conditions (i.e., free walking, and exoskeleton-assisted walking at zero, low,
      and high assistive forces by the use of a unilateral exoskeleton to right lower
      limb). We proposed spatio-spectral representation learning (SSRL), a deep neural
      network topology with shared weights to learn the spatial and spectral
      representations of multi-channel EEG signals during walking. Adoption of weight
      sharing reduces the number of free parameters, while learning spatial and
      spectral equivariant features. SSRL outperformed state-of-the-art methods in
      decoding gait patterns, achieving a classification accuracy of 77.8%. Moreover,
      the features extracted in the intermediate layer of SSRL were observed to be more
      discriminative than the hand-crafted features. When analyzing the weights of the
      proposed model, we found an intriguing spatial distribution that is consistent
      with the distribution found in well-known motor-activated cortical regions. Our
      results show that SSRL advances the ability to decode human locomotion and it
      could have important implications for exoskeleton design, rehabilitation
      processes, and clinical diagnosis.

PMID- 30106680
TI  - A Robotic System for Adaptive Training and Function Assessment of Forelimb
      Retraction in Mice.
AB  - Rodent models are decisive for translational research in healthy and pathological
      conditions of motor function thanks to specific similarities with humans. Here,
      we present an upgraded version of the M-Platform, a robotic device previously
      designed to train mice during forelimb retraction tasks. This new version
      significantly extends its possibilities for murine experiments during motor
      tasks: 1) an actuation system for friction adjustment allows to automatically
      adapt pulling difficulty; 2) the device can be used both for training, with a
      retraction task, and for assessment, with an isometric task; and 3) the platform
      can be integrated with a neurophysiology systems to record simultaneous cortical
      neural activity. Results of the validation experiments with healthy mice
      confirmed that the M-Platform permits precise adjustments of friction during the
      task, thus allowing to change its difficulty and that these variations induce a
      different improvement in motor performance, after specific training sessions.
      Moreover, simultaneous and high quality (high signal-to-noise ratio) neural
      signals can be recorded from the rostral forelimb area (RFA) during task
      execution. With the novel features presented herein, the M-Platform may allow to
      investigate the outcome of a customized motor rehabilitation protocol after
      neural injury, to analyze task-related signals from brain regions interested by
      neuroplastic events and to perform optogenetic silencing or stimulation during
      experiments in transgenic mice.

PMID- 30106681
TI  - Denoising Sparse Autoencoder-Based Ictal EEG Classification.
AB  - Automatic seizure detection technology can automatically mark the EEG by using
      the epileptic detection algorithm, which is helpful to the diagnosis and
      treatment of epileptic diseases. This paper presents an EEG classification
      framework based on the denoising sparse autoencoder. The denoising sparse
      autoencoder (DSAE) is an improved unsupervised deep neural network over sparse
      autoencoder and denoising autoencoder, which can learn the closest representation
      of the data. The sparsity constraint applied in the hidden layer of the network
      makes the expression of data as sparse as possible so as to obtain a more
      efficient representation of EEG signals. In addition, corrupting operation used
      in input data help to enhance the robustness of the system and make it suitable
      for the analysis of non-stationary epileptic EEG signals. In this paper, we first
      imported the pre-processed training data to the DSAE network and trained the
      network. A logistic regression classifier was connected to the top of the DSAE.
      Then, put the test data into the system for classification. Finally, the output
      results of the overall network were post-processed to obtain the final epilepsy
      detection results. In the two-class (nonseizure and seizure EEGs) problem, the
      system has achieved effective results with the average sensitivity of 100%,
      specificity of 100%, and recognition of 100%, showing that the proposed framework
      can be efficient for the classification of epileptic EEGs.

PMID- 30106682
TI  - A Novel Interpretation of Sample Entropy in Surface Electromyographic Examination
      of Complex Neuromuscular Alternations in Subacute and Chronic Stroke.
AB  - The objective of this paper was to develop sample entropy (SampEn) as a novel
      surface electromyogram (EMG) biomarker to quantitatively examine post-stroke
      neuromuscular alternations. The SampEn method was performed on surface EMG
      interference patterns recorded from biceps brachii muscles of nine healthy
      control subjects, fourteen subjects with subacute stroke, and eleven subjects
      with chronic stroke, respectively. Measurements were collected during isometric
      contractions of elbow flexion at different constant force levels. By producing
      diagnostic decisions for individual muscles, two categories of abnormalities in
      some paretic muscles were discriminated in terms of abnormally increased and
      decreased SampEn. The efficiency of the SampEn was demonstrated by its comparable
      performance with a previously reported clustering index (CI) method. Mixed SampEn
      (or CI) patterns were observed in paretic muscles of subjects with stroke
      indicating complex neuromuscular changes at work as a result of a hemispheric
      brain lesion. Although both categories of SampEn (or CI) abnormalities were
      observed in both subacute and chronic stages of stroke, the underlying processes
      contributing to the SampEn abnormalities might vary a lot in stroke stage. The
      SampEn abnormalities were also found in contralateral muscles of subjects with
      chronic stroke indicating the necessity of applying interventions to
      contralateral muscles during stroke rehabilitation. Our work not only presents a
      novel method for quantitative examination of neuromuscular changes, but also
      explains the neuropathological mechanisms of motor impairments and offers
      guidelines for a better design of effective rehabilitation protocols toward
      improved motor recovery.

PMID- 30106683
TI  - Comparing the Use of Single vs. Multiple Combined Abilities in Conducting Complex
      Computer Tasks Hands-free.
AB  - OBJECTIVE: Assistive technologies often focus on a remaining ability of their
      users, particularly those with physical disabilities, e.g. tetraplegia, to
      facilitate their computer access. We hypothesized that by combining multiple
      remaining abilities of the end users in an intuitive fashion, it is possible to
      improve the quality of computer access. In this study, 15 able-bodied subjects
      completed four computer access tasks without using their hands: center-out
      tapping, on-screen maze navigation, playing a game, and sending an email. They
      used the multimodal Tongue Drive System (mTDS), which offers proportional cursor
      control via head motion, discrete clicks via tongue gestures, and typing via
      speech recognition simultaneously. Their performances were compared against
      unimodal tongue gestures (TDS), and Keyboard & Mouse combination (KnM), as the
      gold standard. RESULTS: Center-out tapping task average throughputs using mTDS
      and TDS were 0.84 bps and 0.94 bps, which were 21% and 22.4% of the throughput
      using mouse, respectively, while the average error rate and missed targets using
      mTDS were 4.1% and 25.5% less than TDS. Maze navigation throughputs using mTDS
      and TDS were 0.35 bps and 0.46 bps, which were 16.6% and 21.8% of the throughput
      using mouse, respectively. Participants achieved 72.32% higher score using mTDS
      than TDS when playing a simple game. Average email generating time with mTDS was
      ~2x longer than KnM with a mean typing accuracy of 78.1%. CONCLUSION: Engaging
      multimodal abilities helped participants perform considerably better in complex
      tasks, such as sending an email, compared to a unimodal system (TDS). Their
      performances were similar for simpler task, while multimodal inputs improved
      interaction accuracy. Cursor navigation with head motion led to higher score in
      less constrained tasks, such as game, than a highly constrained maze task.

PMID- 30106684
TI  - Individual characterization of fast intracortical facilitation with paired
      biphasic-wave transcranial magnetic stimulation.
AB  - We characterized the short-interval intracortical facilitation (SICF) via
      modulation of transcranial magnetic stimulation (TMS) induced motor evoked
      potentials (MEPs) using paired-pulse stimulation, and analyzed the interactions
      with known SICF I-wave behavior. The objective was to optimize individual SICF to
      enhance TMS effects in motor mapping and therapeutic stimulations. We applied
      navigated TMS in nine healthy volunteers to study SICF. MEPs were measured for
      baseline using single-pulse TMS, and subsequently, paired-pulse TMS was applied
      to study SICF. The interstimulus interval (ISI) between the pulses was varied
      between 1.2 and 4.3 ms at 0.1 ms intervals. Ten MEPs were measured from three
      muscles (FDI, APB and ADM) in the dominant hand of the volunteer. We then fitted
      a 3-peak Gaussian model to the individual paired-pulse MEP vs. ISI curves to
      characterize each peak by latency, amplitude and width. Individual SICF I-wave
      interaction characteristics were successfully determined. The average peak
      latencies were 1.36 (I1-wave), 2.80 (I2-wave) and 4.29 (I3-wave) for the targeted
      FDI muscle. The peak amplitudes differed depending on the muscle (p = 0.001),
      with ADM muscle exhibiting greatest SICF effect, but no significant difference
      between the three peaks. In addition, the peak widths differed between all
      muscles (p<0.001), second peak being the widest. In conclusion, the individual
      SICF I-wave interaction characteristics were successfully determined revealing
      significant differences in peak features. This could enable application of SICF
      for enhancement of TMS effects in therapy, cortical mapping and basic
      neuroscience applications.

PMID- 30106685
TI  - Label-Free Biomolecule Detection in Physiological Solutions With Enhanced
      Sensitivity Using Graphene Nanogrids FET Biosensor.
AB  - Recently, graphene nanogrid sensor has been reported to be capable of sub
      femtomolar sensing of Hepatitis B (Hep-B) surface antigen in buffer. However, for
      such low concentration of Hep-B in serum, it has been observed during real-time
      operation that there is an overlap of around 50% in the drain-source current
      sensitivity values between different concentrations of the target biomolecule, in
      the range from 0.1 to 100 fM. This has been attributed to the fact that the
      concentration of non-specific antigen in serum being significantly higher than
      that of the target antigen, there is a considerable deviation in the number of
      captured target antigen for the same concentration. Further, this degree of
      overlap varies from one set to another set of sensor, depending on the
      statistical variations in the sensor fabrication process. This phenomenon
      challenges the quantification of target antigen for ultralow limit in
      physiological analyte. In this paper, we introduce probabilistic neural network
      (PNN) for quantification of Hep-B down to 0.1 fM in serum using graphene
      nanogrids field-effect transistor biosensor. The sensor has been operated in
      heterodyne mode in the frequency range of 100 kHz to 1 MHz applied between drain
      and source to overcome the problem of Debye screening effect. The application of
      PNN limits the quantification error within 10% in the range of 0.1 to 100 fM in
      contrast to 77% and 66% using polynomial fit and static neural network models,
      respectively. Further, the proposed methodology lowers the detection limit of Hep
      B in serum by more than three orders of magnitude compared with the state-of-the
      art, real-time, label-free sensors.

PMID- 30106686
TI  - Identifying lncRNA and mRNA Co-expression Modules from Matched Expression Data in
      Ovarian Cancer.
AB  - Long non-coding RNAs (lncRNAs) have been shown to be involved in multiple
      biological processes and play critical roles in tumorigenesis. Numerous lncRNAs
      have been discovered in diverse species, but the functions of most lncRNAs still
      remain unclear. Meanwhile, their expression patterns and regulation mechanisms
      are also far from being fully understood. With the advances of high-throughput
      technologies, the increasing availability of genomic data creates opportunities
      for deciphering the molecular mechanism and underlying pathogenesis of human
      diseases. Here, we develop an integrative framework called JONMF to identify
      lncRNA-mRNA co-expression modules based on the sample-matched lncRNA and mRNA
      expression profiles. We formulate the module detection task as an optimization
      problem with joint orthogonal non-negative matrix factorization that could
      effectively prevent multicollinearity and produce a good modularity
      interpretation. The constructed lncRNA-mRNA co-expression network and the gene
      gene interaction network are used as the network-regularized constraints to
      improve the module accuracy, while the sparsity constraints are simultaneously
      utilized to achieve modular sparse solutions. We applied JONMF to human ovarian
      cancer dataset and the experiment results demonstrate that the proposed method
      can effectively discover biologically functional co-expression modules, which may
      provide insights into the function of lncRNAs and molecular mechanism of human
      diseases.

PMID- 30106687
TI  - End-to-end Representation Learning for Chemical-Chemical Interaction Prediction.
AB  - Chemical-chemical interaction (CCI) plays a major role in predicting candidate
      drugs, toxicities, therapeutic effects, and biological functions. CCI is
      typically inferred from a variety of information; however, CCI has yet not been
      predicted using a learning-based approach. In other drug analyses, deep learning
      has been actively used in recent years. However, in most cases, deep learning has
      been used only for classification even though it has feature extraction
      capabilities. Thus, in this paper, we propose an end-to-end representation
      learning method for CCI, named DeepCCI, which includes feature extraction and a
      learning-based approach. Our proposed architecture is based on the Siamese
      network. Hidden representations are extracted from a simplified molecular input
      line entry system, which is a string notation representing the chemical structure
      using weight-shared convolutional neural networks. Subsequently, L1 element-wise
      distances between the two extracted hidden representations are measured. The
      performance of DeepCCI is compared with those of 12 fingerprint-method
      combinations. The proposed DeepCCI shows the best performance in most of the
      evaluation metrics used. In addition, DeepCCI was experimentally validated to
      guarantee the commutative property. The automatically extracted features can
      alleviate the efforts required for manual feature engineering and improve
      prediction performance.

PMID- 30106688
TI  - Weakly-Supervised Convolutional Neural Network Architecture for Predicting
      Protein-DNA Binding.
AB  - Although convolutional neural networks (CNN) have outperformed conventional
      methods in predicting the sequence specificities of protein-DNA binding in recent
      years, they do not take full advantage of the intrinsic weakly-supervised
      information of DNA sequences that a bound sequence may contain multiple TFBS(s).
      Here, we propose a weakly-supervised convolutional neural network architecture
      (WSCNN), combining multiple-instance learning (MIL) with CNN, to further boost
      the performance of predicting protein-DNA binding. WSCNN first divides each DNA
      sequence into multiple overlapping subsequences (instances) with a sliding
      window, and then separately models each instance using CNN, and finally fuses the
      predicted scores of all instances in the same bag using four fusion methods,
      including Max, Average, Linear Regression, and Top-Bottom Instances. The
      experimental results on in vivo and in vitro datasets illustrate the performance
      of the proposed approach. Moreover, models built on in vitro data using WSCNN can
      predict in vivo protein-DNA binding with good accuracy. In addition, we give a
      quantitative analysis of the importance of the reverse-complement mode in
      predicting in vivo protein-DNA binding, and explain why not directly use advanced
      pooling layers to combine MIL with CNN, through a series of experiments.

PMID- 30106689
TI  - Deep Neural Networks for Exploration of Transcriptome of Adult Mouse Brain.
AB  - Transcriptome in brain plays a crucial role in understanding the cortical
      organization and the development of brain structure and function. Two challenges,
      the incomplete data and the high dimensionality of transcriptome, remain
      unsolved. Here we present a novel training scheme that successfully adapts the U
      net architecture to the problem of volume recovery. By analogy to denoising
      autoencoder, we hide a portion of each training sample so that the network can
      learn to recover missing voxels from the context. Then on the completed volumes,
      we show that restricted Boltzmann Machines (RBMs) can be used to infer co
      occurrences among voxels, providing foundations for dividing the cortex into
      discrete subregions. As we stack multiple RBMs to form a deep belief network
      (DBN), we progressively map the high-dimensional raw input into abstract
      representations and create a hierarchy of transcriptome architecture. A coarse to
      fine organization emerges from the network layers. This organization incidentally
      corresponds to the anatomical structures, suggesting a close link between
      structures and the genetic underpinnings. Thus, we demonstrate a new way of
      learning transcriptome-based hierarchical organization using RBM and DBN.

PMID- 30106690
TI  - Exploring Frequented Regions in Pan-Genomic Graphs.
AB  - We consider the problem of identifying regions within a pan-genome De Bruijn
      graph that are traversed by many sequence paths. We define such regions and the
      subpaths that traverse them as frequented regions (FRs). In this work, we
      formalize the FR problem and describe an efficient algorithm for finding FRs.
      Subsequently, we propose some applications of FRs based on machine-learning and
      pan-genome graph simplification. We demonstrate the effectiveness of these
      applications using data sets for the organisms Staphylococcus aureus (bacterium)
      and Saccharomyces cerevisiae (yeast). We corroborate the biological relevance of
      FRs such as identifying introgressions in yeast that aid in alcohol tolerance,
      and show that FRs are useful for classification of yeast strains by industrial
      use and visualizing pan-genomic space.

PMID- 30106691
TI  - Adjacent Y-ion Ratio Distributions and Its Application in Peptide Sequencing.
AB  - A scoring function plays a critical role in software for peptide identification
      with mass spectrometry. We present a general scoring feature that can be
      incorporated in the scoring functions of other peptide identification software.
      The scoring feature is based on the intensity ratios between two adjacent y-ions
      in the spectrum. A method is proposed to obtain the probability distributions of
      such ratios, and to calculate the scoring feature based on the distributions. To
      demonstrate the performance of the method, the new feature is incorporated with
      X!Tandem and Novor and significantly improved the database search and de novo
      sequencing performances on the testing data, respectively.

PMID- 30106692
TI  - Learning for Personalised Medicine: A Comprehensive Review from Deep Learning
      Perspective.
AB  - With the recent advancements in analysing high volume, complex and unstructured
      data, modern learning methods are playing an increasingly critical role in the
      field of personalised medicine. Personalised medicine, which refers to providing
      tailored medical treatment to individual patients through the identification of
      common features, including their genetics, inheritance, and lifestyle, has
      attracted the attention of many researchers over the recent years. This review
      paper provides an overview of the research progress in application of learning
      methods with the focus on deep learning in personalised medicine. In particular,
      three domains of applications are reviewed, including drug development, disease
      characteristics identification, and therapeutics effect prediction. The main
      objective of this survey is to consider the applied methods in detail and to
      offer insights into their pros and cons. Although having demonstrated advantages
      in coping with data complexity and nonlinearity, and in recognising features and
      associating structural data, the studied learning methods are not a panacea to
      all the medical problems. Hence, we discuss the existing research challenges and
      clarify the future study directions.

PMID- 30106693
TI  - Reliance on haptic assistance reflected in haptic cue weighting.
AB  - When using an automated system, user trust in the automation is an important
      factor influencing performance. Prior studies have analyzed trust during
      supervisory control of automation, and how trust influences reliance: the
      behavioral correlate of trust. Here, we investigated how reliance on haptic
      assistance affects performance during shared control with an automated system.
      Subjects made reaches towards a hidden target using a visual cue and haptic cue
      (assistance from the automation). We sought to influence reliance by changing the
      variability of trial-by-trial random errors in the haptic assistance. Reliance
      was quantified in terms of the subject's position at the end of the reach
      relative to the two cues. Our results show that subjects aimed more towards the
      visual cue when the variability of the haptic cue errors increased, resembling
      cue weighting behavior. Similar behavior was observed both when subjects had
      explicit knowledge about the haptic cue error variability, as well as when they
      had only implicit knowledge (from experience). However, the group with explicit
      knowledge was able to more quickly adapt their reliance on the haptic assistance.
      The method we introduce here provides a quantitative way to study user reliance
      on the information provided by automated systems with shared control.

PMID- 30106694
TI  - Exponential Synchronizationlike Criterion for State-Dependent Impulsive Dynamical
      Networks.
AB  - This paper focuses on the problem of the exponential synchronizationlike criteria
      for state-dependent impulsive dynamical networks (SIDNs). Two types of sufficient
      conditions, which are applied to ensure every solution intersecting each
      impulsive surface exactly once, are derived. For each type of collision
      conditions, combining with comparison principle and inequality techniques, some
      sufficient conditions are obtained to ensure local exponential
      synchronizationlike for SIDN. Moreover, a quiet different impulsive strategy
      concerning the trigger rules of impulsive instants is proposed. Finally, an
      example is given to demonstrate the effectiveness of our results.

PMID- 30106695
TI  - Exponential Synchronization for Delayed Dynamical Networks via Intermittent
      Control: Dealing With Actuator Saturations.
AB  - Over the past two decades, the synchronization problem for dynamical networks has
      drawn significant attention due to its clear practical insight in biological
      systems, social networks, and neuroscience. In the case where a dynamical network
      cannot achieve the synchronization by itself, the feedback controller should be
      added to drive the network toward a desired orbit. On the other hand, the time
      delays may often occur in the nodes or the couplings of a dynamical network, and
      the existence of time delays may induce some undesirable dynamics or even
      instability. Moreover, in the course of implementing a feedback controller, the
      inevitable actuator limitations could downgrade the system performance and, in
      the worst case, destabilize the closed-loop dynamics. The main purpose of this
      paper is to consider the synchronization problem for a class of delayed dynamical
      networks with actuator saturations. Each node of the dynamical network is
      described by a nonlinear system with a time-varying delay and the intermittent
      control strategy is proposed. By using a combination of novel sector conditions,
      piecewise Lyapunov-like functionals and the switched system approach, delay
      dependent sufficient conditions are first obtained under which the dynamical
      network is locally exponentially synchronized. Then, the explicit
      characterization of the controller gains is established by means of the
      feasibility of certain matrix inequalities. Furthermore, optimization problems
      are formulated in order to acquire a larger estimate of the set of initial
      conditions for the evolution of the error dynamics when designing the
      intermittent controller. Finally, two examples are given to show the benefits and
      effectiveness of the developed theoretical results.

PMID- 30106697
TI  - Variational Bayesian Learning of Generalized Dirichlet-Based Hidden Markov Models
      Applied to Unusual Events Detection.
AB  - Learning a hidden Markov model (HMM) is typically based on the computation of a
      likelihood which is intractable due to a summation over all possible combinations
      of states and mixture components. This estimation is often tackled by a
      maximization strategy, which is known as the Baum-Welch algorithm. However, some
      drawbacks of this approach have led to the consideration of Bayesian methods that
      add a prior over the parameters in order to work with the posterior probability
      and the marginal likelihood. These approaches can lead to good models but to the
      cost of extremely long computations (e.g., Markov Chain Monte Carlo). More
      recently, variational Bayesian frameworks have been proposed as a Bayesian
      alternative that keeps the computation tractable and the approximation tight. It
      relies on the introduction of a prior over the parameters to be learned and on an
      approximation of the true posterior distribution. After proving good standing in
      the case of finite mixture models and discrete and Gaussian HMMs, we propose here
      to derive the equations of the variational learning of the Dirichlet mixture
      based HMM, and to extend it to the generalized Dirichlet. The latter case
      presents several properties that make the estimation more accurate. We prove the
      validity of this approach within the context of unusual event detection in public
      areas using the University of California San Diego data sets. HMMs are trained
      over normal video sequences using the typical Baum-Welch approach versus the
      variational one. The variational learning leads to more accurate models for the
      detection and localization of anomaly, and the general HMM approach is shown to
      be versatile enough to handle the detection of various synthetically generated
      tampering events.

PMID- 30106696
TI  - Spatially Regularized Structural Support Vector Machine for Robust Visual
      Tracking.
AB  - Structural support vector machine (SSVM) is popular in the visual tracking field
      as it provides a consistent target representation for both learning and
      detection. However, the spatial distribution of feature is not considered in
      standard SSVM-based trackers, therefore leading to limited performance. To obtain
      a robust discriminative classifier, this paper proposes a novel tracking
      framework that spatially regularizes SSVM, which yields a new spatially
      regularized SSVM (SRSSVM). We utilize the spatial regularization prior to
      penalize the learning classifier with the same size as the target region. The
      location of classifier spatially located far from the center of region is
      assigned large weight and vice versa. Then, it is introduced into the SSVM model
      as a regularization factor to learn the robust discriminative model. Furthermore,
      an optimizing algorithm with dual coordination descent is presented to
      efficiently solve the SRSSVM tracking model. Our proposed SRSSVM tracking method
      has low computational cost like the traditional linear SSVM tracker while can
      significantly improve the robustness of the discriminative classifier. The
      experimental results on three popular tracking benchmark data sets show that the
      proposed SRSSVM tracking method performs favorably against the state-of-the-art
      trackers.

PMID- 30106698
TI  - Semantically Modeling of Object and Context for Categorization.
AB  - Object-centric-based categorization methods have been proven more effective than
      hard partitions of images (e.g., spatial pyramid matching). However, how to
      determine the locations of objects is still an open problem. Besides, modeling of
      context areas is often mixed with the background. Moreover, the semantic
      information is often ignored by these methods that only use visual
      representations for classification. In this paper, we propose an object
      categorization method by semantically modeling the object and context information
      (SOC). We first select a number of candidate regions with high confidence scores
      and semantically represent these regions by measuring correlations of each region
      with prelearned classifiers (e.g., local feature-based classifiers and deep
      convolutional-neural-network-based classifiers). These regions are clustered for
      object selections. The other selected areas are then viewed as context areas. We
      treat other areas beyond the object and context areas within one image as the
      background. The visually and semantically represented objects and contexts are
      then used along with the background area for object representations and
      categorizations. Experimental results on several public data sets well
      demonstrate the effectiveness of the proposed object categorization method by
      semantically modeling the object and context information.

PMID- 30106699
TI  - Multiscaled Fusion of Deep Convolutional Neural Networks for Screening Atrial
      Fibrillation From Single Lead Short ECG Recordings.
AB  - Atrial fibrillation (AF) is one of the most common sustained chronic cardiac
      arrhythmia in elderly population, associated with a high mortality and morbidity
      in stroke, heart failure, coronary artery disease, systemic thromboembolism, etc.
      The early detection of AF is necessary for averting the possibility of disability
      or mortality. However, AF detection remains problematic due to its episodic
      pattern. In this paper, a multiscaled fusion of deep convolutional neural network
      (MS-CNN) is proposed to screen out AF recordings from single lead short
      electrocardiogram (ECG) recordings. The MS-CNN employs the architecture of two
      stream convolutional networks with different filter sizes to capture features of
      different scales. The experimental results show that the proposed MS-CNN achieves
      96.99% of classification accuracy on ECG recordings cropped/padded to 5 s.
      Especially, the best classification accuracy, 98.13%, is obtained on ECG
      recordings of 20 s. Compared with artificial neural network, shallow single
      stream CNN, and VisualGeometry group network, the MS-CNN can achieve the better
      classification performance. Meanwhile, visualization of the learned features from
      the MS-CNN demonstrates its superiority in extracting linear separable ECG
      features without hand-craft feature engineering. The excellent AF screening
      performance of the MS-CNN can satisfy the most elders for daily monitoring with
      wearable devices.

PMID- 30106700
TI  - Iterative Design of Visual Analytics for a Clinician-in-the-loop Smart Home.
AB  - In order to meet the health needs of the coming "age wave", technology needs to
      be designed that supports remote health monitoring and assessment. In this study
      we design CIL, a clinician-in-the-loop visual interface, that provides clinicians
      with patient behavior patterns, derived from smart home data. A total of 60
      experienced nurses participated in an iterative design of an interactive
      graphical interface for remote behavior monitoring. Results of the study indicate
      that usability of the system improves over multiple iterations of participatory
      design. In addition, the resulting interface is useful for identifying behavior
      patterns that are indicative of chronic health conditions and unexpected health
      events. This technology offers the potential to support self-management and
      chronic conditions, even for individuals living in remote locations.

PMID- 30106701
TI  - Multiday Evaluation of Techniques for EMG Based Classification of Hand Motions.
AB  - Currently, most of the adopted myoelectric schemes for upper limb prostheses do
      not provide users with intuitive control. Higher accuracies have been reported
      using different classification algorithms but investigation on the reliability
      over time for these methods is very limited. In this study, we compared for the
      first time the longitudinal performance of selected state-of-the-art techniques
      for Electromyography (EMG) based classification of hand motions. Experiments were
      conducted on ten able-bodied and six transradial amputees for seven continuous
      days. Linear Discriminant Analysis (LDA), Artificial Neural Network (ANN),
      Support Vector Machine (SVM), K-Nearest Neighbour (KNN) and Decision Trees (TREE)
      were compared. Comparative analysis showed that the ANN attained highest
      classification accuracy followed by LDA. Three-way repeated ANOVA test showed a
      significant difference ($?rm P?lt 0.001$) between EMG types (surface,
      intramuscular and combined), Days (1-7), classifiers and their interactions.
      Performance on last day was significantly better ($?rm P?lt 0.05$) than the first
      day for all classifiers and EMG types. Within-day classification error (WCE)
      across all subject and days in ANN was: surface (9.12 +/- 7.38%), intramuscular
      (11.86+/-7.84%) and combined (6.11+/-7.46%). The between-day analysis in a leave
      one-day-out fashion showed that ANN was the optimal classifier (surface (21.88 +/
      4.14%) intramuscular (29.33 +/- 2.58%) and combined (14.37 +/- 3.10%)). Results
      indicate that that within day performances of classifiers may be similar but over
      time it may lead to a substantially different outcome. Furthermore, training ANN
      on multiple days might allow capturing time-dependent variability in the EMG
      signals and thus minimizing the necessity for daily system recalibration.

PMID- 30106702
TI  - Monitoring Health Status in Long Term Care Through the Use of Ambient
      Technologies and Serious Games.
AB  - New technologies, such as serious games and ambient activities, are being
      developed to address problems of under-stimulation, anxiety, and agitation in
      millions of people living with dementia in long term care homes. Frequent
      interactions with instrumented versions of these technologies may not only be
      beneficial for long term care residents, but may also provide a valuable new set
      of multifaceted data related to the health status of residents over time. In this
      paper, we develop a model for health monitoring in healthcare environments and we
      report on two studies that show how medically relevant data can be collected from
      elderly residents and emergency department patients in an unobtrusive way. The
      first study shows how data related to cognitive abilities can be collected from
      elderly emergency department patients and the second study shows how detailed
      data on a range of factors can be collected from ambient activity units designed
      to provide engaging interactions for long term care residents. In summary, this
      paper proposes the use of new technologies to transform long term care from a
      data poor to a data rich environment, where the health status of long term care
      residents and elderly patients is more closely monitored.

PMID- 30106703
TI  - A Kinematic Model for Swarm Finite-Time Trajectory Tracking.
AB  - This paper focuses on the trajectory tracking problem for a swarm of mobile
      agents. A kinematic model describing the interactions and evolutions of the swarm
      members is proposed and its main properties are analyzed emphasizing that the
      agents centroid is ensured to track in finite-time a given reference trajectory
      and that the agents reach an aggregation in finite-time in a hyper-ball moving
      around the centroid path. One of the main characteristics of the model is the
      presence of an interaction matrix, between agents coordinates, which allows to
      define some properties of the swarm allowing the creation of different forms of
      agents aggregations, i.e., spheres, ellipsoids, straight lines, etc. Indeed swarm
      properties related to the agents configuration around the performed path along
      with agents interactions and absence of collisions are analyzed depending on the
      chosen interaction matrix.

PMID- 30106704
TI  - Quasi-Synchronization of Delayed Memristive Neural Networks via Region
      Partitioning-Dependent Intermittent Control.
AB  - This paper aims at investigating the master-slave quasi-synchronization of
      delayed memristive neural networks (MNNs) by proposing a region-partitioning
      dependent intermittent control. The proposed method is described by three
      partitions of non-negative real region and an auxiliary positive definite
      function. Whether the control input is imposed on the slave system or not is
      decided by the dynamical relationships among the three subregions and the
      auxiliary function. From these ingredients, several succinct criteria with the
      associated co-design procedure are presented such that the synchronization error
      converges to a predetermined level. The proposed intermittent control scheme is
      also applied to the event-triggered control, and an intermittent event-triggered
      mechanism is devised to investigate the quasi-synchronization of MNNs
      correspondingly. Such mechanism eliminates the events in rest time, and then it
      reduces the amount of samplings. Finally, two illustrative examples are presented
      to verify the effectiveness of our theoretical results.

PMID- 30106705
TI  - Flow Fields: Dense Correspondence Fields for Highly Accurate Large Displacement
      Optical Flow Estimation.
AB  - Modern large displacement optical flow algorithms usually use an initialization
      by either sparse descriptor matching techniques or dense approximate nearest
      neighbor fields. While the latter have the advantage of being dense, they have
      the major disadvantage of being very outlier-prone as they are not designed to
      find the optical flow, but the visually most similar correspondence. In this
      article we present a dense correspondence field approach that is much less
      outlier-prone and thus much better suited for optical flow estimation than
      approximate nearest neighbor fields. Our approach does not require explicit
      regularization, smoothing (like median filtering) or a new data term. Instead we
      solely rely on patch matching techniques and a novel multi-scale matching
      strategy. We also present enhancements for outlier filtering. We show that our
      approach is better suited for large displacement optical flow estimation than
      modern descriptor matching techniques. We do so by initializing EpicFlow with our
      approach instead of their originally used state-of-the-art descriptor matching
      technique. We significantly outperform the original EpicFlow on MPI-Sintel, KITTI
      2012, KITTI 2015 and Middlebury. In this extended article of our former
      conference publication we further improve our approach in matching accuracy as
      well as runtime and present more experiments and insights.

PMID- 30106706
TI  - Deep Supervision with Intermediate Concepts.
AB  - Recent data-driven approaches to scene interpretation predominantly pose
      inference as an end-to-end black-box mapping, commonly performed by a
      Convolutional Neural Network (CNN). However, decades of work on perceptual
      organization in both human and machine vision suggest that there are often
      intermediate representations that are intrinsic to an inference task, and which
      provide essential structure to improve generalization. In this work, we explore
      an approach for injecting prior domain structure into neural network training by
      supervising hidden layers of a CNN with intermediate concepts that normally are
      not observed in practice. We formulate a probabilistic framework which formalizes
      these notions and predicts improved generalization via this deep supervision
      method. One advantage of this approach is that we are able to train only from
      synthetic CAD renderings of cluttered scenes, where concept values can be
      extracted, but apply the results to real images. Our implementation achieves the
      state-of-the-art performance of 2D/3D keypoint localization and image
      classification on real image benchmarks including KITTI, PASCAL VOC, PASCAL3D+,
      IKEA, and CIFAR100. We provide additional evidence that our approach outperforms
      alternative forms of supervision, such as multi-task networks.

PMID- 30106707
TI  - Visual Tracking via Dynamic Graph Learning.
AB  - Existing visual tracking methods usually localize a target object with a bounding
      box, in which the performance of the foreground object trackers or detectors is
      often affected by the inclusion of background clutter. To handle this problem, we
      learn a patch-based graph representation for visual tracking. The tracked object
      is modeled by with a graph by taking a set of non-overlapping image patches as
      nodes, in which the weight of each node indicates how likely it belongs to the
      foreground and edges are weighted for indicating the appearance compatibility of
      two neighboring nodes. This graph is dynamically learned and applied in object
      tracking and model updating. The proposed algorithm performs three main steps in
      each frame. First, the graph is initialized by assigning binary weights of some
      image patches to indicate the object and background patches according to the
      predicted bounding box. Second, the graph is optimized to refine the patch
      weights. Third, the object feature representation is updated by imposing the
      weights of patches on the extracted image features. The object location is
      predicted by maximizing the classification score in the structured support vector
      machine. Extensive experiments show that the proposed tracking algorithm performs
      well against the state-of-the-art methods.

PMID- 30106708
TI  - Fast and Accurate Image Super-Resolution with Deep Laplacian Pyramid Networks.
AB  - Convolutional neural networks have recently demonstrated high-quality
      reconstruction for single image super-resolution. However, existing methods often
      require a large number of network parameters and entail heavy computational loads
      at runtime for generating high-accuracy super-resolution results. In this paper,
      we propose the deep Laplacian Pyramid Super-Resolution Network for fast and
      accurate image super-resolution. The proposed network progressively reconstructs
      the sub-band residuals of high-resolution images at multiple pyramid levels. In
      contrast to existing methods that involve the bicubic interpolation for pre
      processing (which results in large feature maps), the proposed method directly
      extracts features from the low-resolution input space and thereby entails low
      computational loads. We train the proposed network with deep supervision using
      the robust Charbonnier loss functions and achieve high-quality image
      reconstruction. Furthermore, we utilize the recursive layers to share parameters
      across as well as within pyramid levels, and thus drastically reduce the number
      of parameters. Extensive quantitative and qualitative evaluations on benchmark
      datasets show that the proposed algorithm performs favorably against the state-of
      the-art methods in terms of run-time and image quality.

PMID- 30106709
TI  - Robust Visual Tracking via Hierarchical Convolutional Features.
AB  - Visual tracking is challenging as target objects often undergo significant
      appearance changes caused by deformation, abrupt motion, background clutter and
      occlusion. In this paper, we propose to exploit the rich hierarchical features of
      deep convolutional neural networks to improve the accuracy and robustness of
      visual tracking. Deep neural networks trained on object recognition datasets
      consist of multiple convolutional layers. These layers encode target appearance
      with different levels of abstraction. For example, the outputs of the last
      convolutional layers encode the semantic information of targets and such
      representations are invariant to significant appearance variations. However,
      their spatial resolutions are too coarse to precisely localize the target. In
      contrast, features from earlier convolutional layers provide more precise
      localization but are less invariant to appearance changes. We interpret the
      hierarchical features of convolutional layers as a nonlinear counterpart of an
      image pyramid representation and explicitly exploit these multiple levels of
      abstraction to represent target objects. Specifically, we learn adaptive
      correlation filters on the outputs from each convolutional layer to encode the
      target appearance. We infer the maximum response of each layer to locate targets
      in a coarse-to-fine manner. To further handle the issues with scale estimation
      and re-detecting target objects from tracking failures caused by heavy occlusion
      or out-of-the-view movement, we conservatively learn another correlation filter,
      that maintains a long-term memory of target appearance, as a discriminative
      classifier. We apply the classifier to two types of object proposals: (1)
      proposals with a small step size and tightly around the estimated location for
      scale estimation; and (2) proposals with large step size and across the whole
      image for target re-detection. Extensive experimental results on large-scale
      benchmark datasets show that the proposed algorithm performs favorably against
      the state-of-the-art tracking methods.

PMID- 30106710
TI  - Convolutional neural network architecture for geometric matching.
AB  - We address the problem of determining correspondences between two images in
      agreement with a geometric model such as an affine, homography or thin-plate
      spline transformation, and estimating its parameters. The contributions of this
      work are three-fold. First, we propose a convolutional neural network
      architecture for geometric matching. The architecture is based on three main
      components that mimic the standard steps of feature extraction, matching and
      simultaneous inlier detection and model parameter estimation, while being
      trainable end-to-end. Second, we demonstrate that the network parameters can be
      trained from synthetically generated imagery without the need for manual
      annotation and that our matching layer significantly increases generalization
      capabilities to never seen before images. Finally, we show that the same model
      can perform both instance-level and category-level matching giving state-of-the
      art results on the challenging PF, TSS and Caltech-101 datasets.

PMID- 30106711
TI  - FissureNet: A Deep Learning Approach For Pulmonary Fissure Detection in CT
      Images.
AB  - Pulmonary fissure detection in computed tomography (CT) is a critical component
      for automatic lobar segmentation. The majority of fissure detection methods use
      feature descriptors that are hand-crafted, low-level, and have local spatial
      extent. The design of such feature detectors is typically targeted towards normal
      fissure anatomy, yielding low sensitivity to weak and abnormal fissures that are
      common in clinical datasets. Furthermore, local features commonly suffer from low
      specificity, as the complex textures in the lung can be indistinguishable from
      the fissure when global context is not considered. We propose a supervised
      discriminative learning framework for simultaneous feature extraction and
      classification. The proposed framework, called FissureNet, is a coarse-to-fine
      cascade of two convolutional neural networks. The coarse-to-fine strategy
      alleviates the challenges associated with training a network to segment a thin
      structure that represents a small fraction of the image voxels. FissureNet was
      evaluated on a cohort of 3706 subjects with inspiration and expiration 3DCT scans
      from the COPDGene clinical trial and a cohort of 20 subjects with 4DCT scans from
      a lung cancer clinical trial. On both datasets, FissureNet showed superior
      performance compared to a deep learning approach using the U-Net architecture and
      a Hessian-based fissure detection method in terms of area under the
      precisionrecall curve (PR-AUC). The overall PR-AUC for FissureNet, UNet, and
      Hessian on the COPDGene (lung cancer) dataset was 0.980 (0.966), 0.963 (0.937),
      and 0.158 (0.182), respectively. On a subset of 30 COPDGene scans, FissureNet was
      compared to a recently proposed advanced fissure detection method called
      derivative of sticks (DoS) and showed superior performance with a PR-AUC of 0.991
      compared to 0.668 for DoS.

PMID- 30106712
TI  - Efficient B-mode Ultrasound Image Reconstruction from Sub-sampled RF Data using
      Deep Learning.
AB  - In portable, three dimensional, and ultra-fast ultrasound imaging systems, there
      is an increasing demand for the reconstruction of high quality images from a
      limited number of radio-frequency (RF) measurements due to receiver (Rx) or
      transmit (Xmit) event sub-sampling. However, due to the presence of side lobe
      artifacts from RF sub-sampling, the standard beamformer often produces blurry
      images with less contrast, which are unsuitable for diagnostic purposes. Existing
      compressed sensing approaches often require either hardware changes or
      computationally expensive algorithms, but their quality improvements are limited.
      To address this problem, here we propose a novel deep learning approach that
      directly interpolates the missing RF data by utilizing redundancy in the Rx-Xmit
      plane. Our extensive experimental results using sub-sampled RF data from a multi
      line acquisition B-mode system confirm that the proposed method can effectively
      reduce the data rate without sacrificing image quality.

PMID- 30106713
TI  - An Empirical Data Inconsistency Metric (DIM) Driven CT Image Reconstruction
      Method.
AB  - Current CT image reconstruction methods generally assume that a complete and
      consistent data set was acquired during data acquisition. In practice, however,
      the acquired data are often not consistent from one view angle to another. In
      this case, the application of a well developed image reconstruction algorithm to
      an inconsistent data set still generates artifacts in the reconstructed images.
      Therefore, it is highly desirable to develop a simple method to classify the
      acquired data set into several consistency classes and to incorporate the data
      consistency information into an image reconstruction framework to simultaneously
      reconstruct several sub-images of the same image object according to the data
      consistency level of the acquired data set. In this work, an empirical data
      inconsistency metric (DIM) was introduced to characterize the inconsistency level
      of the acquired cone beam CT projection data at each view angle caused by the
      polychromatic x-ray spectrum and the use of tube potential modulation. The entire
      acquired data set is then sorted into several subsets of view angles based upon
      the value of the DIM at each view angle. After data classification, the
      previously published algorithm, synchronized multiartifact reduction with
      tomographic reconstruction (SMART-RECON), was applied to simultaneously
      reconstruct images for these subimages in different spectral consistency classes.
      Each sub-image is consistent with the subset of the projection view angles for a
      given range of DIM values. To validate the method, numerical simulation studies
      from an anthropomorphic numerical phantom, a hybrid phantom of known truth with
      human anatomy, and in vivo human subject data were conducted to demonstrate the
      practical utility of the proposed method.

PMID- 30106714
TI  - Pelvic Organ Segmentation Using Distinctive Curve Guided Fully Convolutional
      Networks.
AB  - Accurate segmentation of pelvic organs (i.e., prostate, bladder and rectum) from
      CT image is crucial for effective prostate cancer radiotherapy. However, it is a
      challenging task due to 1) low soft tissue contrast in CT images and 2) large
      shape and appearance variations of pelvic organs. In this paper, we employ a two
      stage deep learning based method, with a novel distinctive curve guided fully
      convolutional network (FCN), to solve the aforementioned challenges.
      Specifically, the first stage is for fast and robust organ detection in the raw
      CT images. It is designed as a coarse segmentation network to provide region
      proposals for three pelvic organs. The second stage is for fine segmentation of
      each organ, based on the region proposal results. To better identify those
      indistinguishable pelvic organ boundaries, a novel morphological representation,
      namely distinctive curve, is also introduced to help better conduct the precise
      segmentation. To implement this, in this second stage, a multi-task FCN is
      initially utilized to learn the distinctive curve and the segmentation map
      separately, and then combine these two tasks to produce accurate segmentation
      map. The final segmentation results of all three pelvic organs are generated by a
      weighted max-voting strategy. We have conducted exhaustive experiments on a large
      and diverse pelvic CT dataset for evaluating our proposed method. The
      experimental results demonstrate that our proposed method is accurate and robust
      for this challenging segmentation task, by also outperforming the state-of-the
      art segmentation methods.

PMID- 30106715
TI  - CONtrast Conformed Electrical Properties Tomography (CONCEPT) based on Multi
      channel Transmission and Alternating Direction Method of Multipliers.
AB  - In Magnetic Resonance based Electrical Properties Tomography (EPT), circularly
      polarized magnetic field B1 from a transmit radiofrequency (RF) coil is measured
      and utilized to infer the electrical conductivity and permittivity of biological
      tissues. Compared to a quadrature RF coil, a multi-channel transmit coil provides
      a plurality of unique transmit B1 patterns that help to alleviate the under
      determined-ness of EPT reconstruction problem, and it also allows to circumvent
      the "transceive phase assumption" that fails at ultra-high-field MRI. Here, a new
      approach, CONtrast Conformed Electrical Properties Tomography or CONCEPT, is
      proposed based on multi-channel transmission that retrieves electrical properties
      (EPs) by solving a linear partial differential equation with discriminated L1 and
      L2 norm regularization informed by intermediate EP gradient. The theory of
      CONCEPT and a fast reconstruction algorithm based on Alternating Direction Method
      of Multipliers are described and evaluated using numerical simulations, phantom
      experiment and analysis of in vivo human brain data at 7 T MRI. Compared to multi
      channel gradient-based EPT (gEPT) method, this new technology does not require
      receive B1 sensitivity profiles and does not rely on symmetry assumption
      regarding RF coil design and imaged target. Moreover, it is not dependent on
      external prior information, such as integration seed point or anatomical MRI,
      which can be sources of bias in reconstructed EP values. By deriving EPs from
      transmit B1 profiles only, CONCEPT can be used with RF coils that include receive
      only arrays with large channel count which can, in turn, offer substantial gains
      in Signal to Noise Ratio. It also holds potentials to image unsymmetrical body
      organs and diseased brain. CONCEPT provides solutions for the practical problems
      during the implementation of gEPT, thus representing a more generalized framework
      in the context of multi-channel RF transmission.

PMID- 30106716
TI  - An Efficient Iterative Cerebral Perfusion CT Reconstruction via Low-Rank Tensor
      Decomposition with Spatial-Temporal Total Variation Regularization.
AB  - Cerebrovascular diseases, i.e., acute stroke, are a common cause of serious long
      term disability. Cerebral perfusion computed tomography (CPCT) can provide rapid,
      highresolution, quantitative hemodynamic maps to assess and stratify perfusion in
      patients with acute stroke symptoms. However, CPCT imaging typically involves a
      substantial radiation dose due to its repeated scanning protocol. Therefore, in
      this work, we present a low-dose CPCT image reconstruction method to yield high
      quality CPCT images and high-precision hemodynamic maps by utilizing the great
      similarity information among the repeated scanned CPCT images. Specifically, a
      newly developed low-rank tensor decomposition with spatial-temporal total
      variation (LRTD-STTV) regularization is incorporated into the reconstruction
      model. In the LRTD-STTV regularization, the tensor Tucker decomposition is used
      to describe global spatialtemporal correlations hidden in the sequential CPCT
      images, and it is superior to the matricization model (i.e., low-rank model) that
      fails to fully investigate the prior knowledge of the intrinsic structures of the
      CPCT images after vectorizing the CPCT images. Moreover, the spatial-temporal TV
      regularization is used to characterize the local piecewise smooth structure in
      the spatial domain and the pixels' similarity with the adjacent frames in the
      temporal domain because the intensity at each pixel in CPCT images is similar to
      its neighbors. Therefore, the presented LRTD-STTV model can efficiently deliver
      faithful underlying information of the CPCT images and preserve the spatial
      structures. An efficient alternating direction method of multipliers algorithm is
      also developed to solve the presented LRTD-STTV model. Extensive experimental
      results on numerical phantom and patient data clearly demonstrated that the
      presented model can significantly improve the quality of CPCT images and provide
      accurate diagnostic features in hemodynamic maps for low-dose cases compared with
      the existing popular algorithms.

PMID- 30106717
TI  - Optimizing a Parameterized Plug-and-Play ADMM for Iterative Low-Dose CT
      Reconstruction.
AB  - Reducing the exposure to X-ray radiation while maintaining a clinically
      acceptable image quality is desirable in various CT applications. To realize low
      dose CT (LdCT) imaging, model-based iterative reconstruction (MBIR) algorithms
      are widely adopted, but they require proper prior knowledge assumptions in the
      sinogram and/or image domains and involve tedious manual optimization of multiple
      parameters. In this work, we propose a deep learning (DL)-based strategy for MBIR
      to simultaneously address prior knowledge design and MBIR parameter selection in
      one optimization framework. Specifically, a parameterized plug-and-play
      alternating direction method of multipliers (3pADMM) is proposed for the general
      penalized weighted least-squares (PWLS) model, and then, by adopting the basic
      idea of DL, the parameterized plug-and-play (3p) prior and the related parameters
      are optimized simultaneously in a single framework using a large number of
      training data. The main contribution of this work is that the 3p prior and the
      related parameters in the proposed 3pADMM framework can be supervised and
      optimized simultaneously to achieve robust LdCT reconstruction performance.
      Experimental results obtained on clinical patient datasets demonstrate that the
      proposed method can achieve promising gains over existing algorithms for LdCT
      image reconstruction in terms of noise-induced artifact suppression and edge
      detail preservation.

PMID- 30106718
TI  - CBCT of a Moving Sample from X-rays and Multiple Videos.
AB  - In this paper we consider dense volumetric modeling of moving samples such as
      body parts. Most dense modeling methods consider samples observed with a moving X
      ray device and cannot easily handle moving samples. We propose instead a novel
      method to observe shape motion from a fixed X-ray device and to build dense in
      depth attenuation information. This yields a low-cost, low-dose 3D imaging
      solution, taking benefit of equipment widely available in clinical environments.
      Our first innovation is to combine a video-based surface motion capture system
      with a single low-cost/low-dose fixed planar X-ray device, in order to retrieve
      the sample motion and attenuation information with minimal radiation exposure.
      Our second innovation is to rely on Bayesian inference to solve for a dense
      attenuation volume given planar radioscopic images of a moving sample. This
      approach enables multiple sources of noise to be considered and takes advantage
      of very limited prior information to solve an otherwise ill-posed problem.
      Results show that the proposed strategy is able to reconstruct dense volumetric
      attenuation models from a very limited number of radiographic views over time on
      synthetic and in-situ data.

PMID- 30106719
TI  - MoDL: Model Based Deep Learning Architecture for Inverse Problems.
AB  - We introduce a model-based image reconstruction framework with a convolution
      neural network (CNN) based regularization prior. The proposed formulation
      provides a systematic approach for deriving deep architectures for inverse
      problems with the arbitrary structure. Since the forward model is explicitly
      accounted for, a smaller network with fewer parameters is sufficient to capture
      the image information compared to direct inversion approaches, thus reducing the
      demand for training data and training time. Since we rely on end-to-end training
      with weight sharing across iterations, the CNN weights are customized to the
      forward model, thus offering improved performance over approaches that rely on
      pre-trained denoisers. Our experiments show that the decoupling of the number of
      iterations from the network complexity offered by this approach provides benefits
      including lower demand for training data, reduced risk of overfitting, and
      implementations with significantly reduced memory footprint. We propose to
      enforce data-consistency by using numerical optimization blocks such as conjugate
      gradients algorithm within the network; this approach offers faster convergence
      per iteration, compared to methods that rely on proximal gradients steps to
      enforce data consistency. Our experiments show that the faster convergence
      translates to improved performance, primarily when the available GPU memory
      restricts the number of iterations.

PMID- 30106720
TI  - Suppression of Dick Effect in Ramsey-CPT Atomic Clock by Interleaving Lock.
AB  - The Dick effect is one of the main limitations of short-term frequency stability
      for most atomic clocks operating in the pulsed mode. Rather than employing better
      local oscillators with ultralow phase noise, using the interleaving lock
      technique to eliminate the dead time is a promising approach to suppress the Dick
      effect. In this paper, we demonstrate the suppression of the Dick effect by the
      interleaving lock technique in a pulsed Ramsey-coherent population trapping clock
      with two identical Cs atomic ensembles. The Dick effect is expected to be reduced
      by a factor of 24 theoretically. The measured short-term Allan deviation is
      improved from at 1 s to at 1 s. What is even more remarkable is that the Allan
      deviation curve exhibits slope from 0.01 to 2 s.

PMID- 30106721
TI  - Design and Fabrication of a Miniaturized Convex Array for Combined Ultrasound and
      Photoacoustic Imaging of the Prostate.
AB  - Although transrectal ultrasound (TRUS) imaging is widely used for screening and
      diagnosing prostate cancer, it is often not found on TRUS images, depending on
      its stage, size, and location. In addition, due to the weak echo signal and the
      low contrast of TRUS images, it is difficult to diagnose early-stage prostate
      cancers and distinguish malignant tumors from benign prostatic hyperplasia. For
      this reason, TRUS image-guided biopsy is mandatory to confirm the malignancy of
      the suspicious tumor, but the diagnostic accuracy of initial biopsy is only 20%
      30%, so that the patients inevitably undergo repeated biopsies. TRUS
      photoacoustic (TRUS-PA) imaging is one way to resolve those problems. However,
      the development of a TRUS-PA probe, in which an ultrasound array transducer and
      optical fibers are integrated, is demanding because the overall size of the probe
      should be as small as possible for the convenience of the patients, while
      providing the desired performances. Here, we report a recently developed TRUS-PA
      probe. The core element of the TRUS-PA is a miniaturized 128-element, 7-MHz
      convex array transducer of which size in the lateral and elevational directions
      is 11.4 and 5 mm, respectively. A new concept of a flexible printed circuit board
      was also developed to limit the size of the TRUS-PA probe to less than 15 mm.
      From the performance evaluation, it was found that the developed array with a
      field-of-view of 134 degrees  has a center frequency of 6.75 MHz, a -6-dB
      fractional bandwidth of 66%, and a crosstalk of less than -45 dB. In the tissue
      mimicking phantom test and ex vivo experiments, the miniaturized convex array
      proved to be capable of providing combined US and PA images with acceptable
      imaging quality in spite of its small size.

PMID- 30106722
TI  - A Self-Propelled Mechanism to Increase Range of Bistable Operation of a
      Piezoelectric Cantilever-Based Vibration Energy Harvester.
AB  - In our previous works, we presented a method to increase the harvested energy
      from vibrations using a piezoelectric cantilever and to increase the frequency
      range of operation by introducing bistability with the use of magnetic repulsion.
      However, for small excitations, the cantilever may not be able to overcome the
      magnetic repulsive force but vibrate at one of its two equilibrium positions with
      reduced amplitude. This work introduces a method of increasing the range of
      excitations over which the operation remains bistable. This is achieved by spring
      loading one of the magnets, previously on a fixed support, allowing motion in one
      dimension only, toward and away from the cantilever in the horizontal plane.
      Configured so, as the cantilever moves toward this magnet, the repulsion due to
      the cantilever-mounted magnet pushes the spring-loaded magnet away, increasing
      distance, and thus, reducing magnetic force between them, required to be overcome
      by external excitations for bistable operation. Similarly, as the cantilever
      moves away, the spring pushes the magnet closer to the cantilever-mounted magnet,
      increasing vibration amplitude. Thus, the spring introduces a negative feedback
      which favors bistable operation over an increased range of excitations. This
      completely mechanical method requires no additional energy cost. Peak power gains
      of up to 90 and a decrease in excitation voltage of up to 60% were observed over
      the fixed magnet.

PMID- 30106723
TI  - Mechanical Anisotropy Assessment in Kidney Cortex Using ARFI Peak Displacement:
      Preclinical Validation and Pilot In Vivo Clinical Results in Kidney Allografts.
AB  - The kidney is an anisotropic organ, with higher elasticity along versus across
      nephrons. The degree of mechanical anisotropy in the kidney may be diagnostically
      relevant if properly exploited; however, if improperly controlled, anisotropy may
      confound stiffness measurements. The purpose of this study is to demonstrate the
      clinical feasibility of Acoustic Radiation Force (ARF) induced peak displacement
      (PD) measures for both exploiting and obviating mechanical anisotropy in the
      cortex of human kidney allografts, in vivo. Validation of the imaging methods is
      provided by pre-clinical studies in pig kidneys, in which ARF-induced PD values
      were statistically significantly higher (p<0.01, Wilcoxon) when the transducer
      executing asymmetric ARF was oriented across versus along the nephrons. The ratio
      of these PD values obtained with the transducer oriented across versus along the
      nephrons strongly linearly correlated (R2 = 0.95) to the ratio of shear moduli
      measured by shear wave elasticity imaging (SWEI). On the contrary, when a
      symmetric ARF was implemented, no statistically significant difference in PD was
      observed (p>0.01). Similar results were demonstrated in vivo in the kidney
      allografts of 14 patients. The symmetric ARF produced PD measures with no
      statistically significant difference (p>0.01) between along versus across
      alignments, but the asymmetric ARF yielded PD ratios that remained constant over
      a six-month observation period post-transplantation, consistent with stable serum
      creatinine level and urine protein to creatinine ratio in the same patient
      population (p>0.01). The results of this pilot in vivo clinical study suggest the
      feasibility of: 1) implementing symmetrical ARF to obviate mechanical anisotropy
      in the kidney cortex when anisotropy is a confounding factor, and 2) implementing
      asymmetric ARF to exploit mechanical anisotropy when mechanical anisotropy is a
      potentially relevant biomarker.

PMID- 30106724
TI  - Backtracking Spatial Pyramid Pooling (SPP)-based Image Classifier for Weakly
      Supervised Top-down Salient Object Detection.
AB  - Top-down saliency models produce a probability map that peaks at target locations
      specified by a task/goal such as object detection. They are usually trained in a
      fully supervised setting involving pixel-level annotations of objects. We propose
      a weakly supervised top-down saliency framework using only binary labels that
      indicate the presence/absence of an object in an image. First, the probabilistic
      contribution of each image region to the confidence of a CNN-based image
      classifier is computed through a backtracking strategy to produce top-down
      saliency. From a set of saliency maps of an image produced by fast bottom-up
      saliency approaches, we select the best saliency map suitable for the top-down
      task. The selected bottom-up saliency map is combined with the top-down saliency
      map. Features having high combined saliency are used to train a linear SVM
      classifier to estimate feature saliency. This is integrated with combined
      saliency and further refined through a multi-scale superpixel-averaging of
      saliency map. We evaluate the performance of the proposed weakly supervised
      topdown saliency and achieve comparable performance with fully supervised
      approaches. Experiments are carried out on seven challenging datasets and
      quantitative results are compared with 40 closely related approaches across 4
      different applications. Code will be made publicly available.

PMID- 30106725
TI  - Deep Discrete Supervised Hashing.
AB  - Hashing has been widely used for large-scale search due to its low storage cost
      and fast query speed. By using supervised information, supervised hashing can
      significantly outperform unsupervised hashing. Recently, discrete supervised
      hashing and feature learning based deep hashing are two representative progresses
      in supervised hashing. On one hand, hashing is essentially a discrete
      optimization problem. Hence, utilizing supervised information to directly guide
      discrete (binary) coding procedure can avoid sub-optimal solution and improve the
      accuracy. On the other hand, feature learning based deep hashing, which
      integrates deep feature learning and hash-code learning into an end-to-end
      architecture, can enhance the feedback between feature learning and hash-code
      learning. The key in discrete supervised hashing is to adopt supervised
      information to directly guide the discrete coding procedure in hashing. The key
      in deep hashing is to adopt the supervised information to directly guide the deep
      feature learning procedure. However, most deep supervised hashing methods cannot
      use the supervised information to directly guide both discrete (binary) coding
      procedure and deep feature learning procedure in the same framework. In this
      paper, we propose a novel deep hashing method, called deep discrete supervised
      hashing (DDSH). DDSH is the first deep hashing method which can utilize pairwise
      supervised information to directly guide both discrete coding procedure and deep
      feature learning procedure and thus enhance the feedback between these two
      important procedures. Experiments on four real datasets show that DDSH can
      outperform other state-of-the-art baselines, including both discrete hashing and
      deep hashing baselines, for image retrieval.

PMID- 30106726
TI  - Efficient and Robust Direct Image Registration Based on Joint Geometric and
      Photometric Lie Algebra.
AB  - This paper considers the joint geometric and photometric image registration
      problem. The inverse compositional (IC) algorithm and the efficient second-order
      minimization (ESM) algorithm are two typical efficient methods applied to the
      geometric registration problem. Their efficiency stems from the utilization of
      the group structure of geometric transformations. To allow for photometric
      variations, the dual IC algorithm (DIC) proposed by Bartoli performs joint
      geometric and photometric image registration by extending the IC algorithm. The
      group structures of both geometric and photometric transformations are exploited.
      Despite the robustness to large photometric variations, DIC is vulnerable to
      large geometric deformations. The ESM algorithm is extended by Silveira et al. to
      address photometric variations. In their approach, the photometric
      transformations are modeled in Euclidean space. Their approach is robust to
      relatively large geometric and photometric transformations; however, it is not
      efficient for large photometric variations. We propose a new efficient and robust
      image registration method by exploiting the non-Euclidean Lie group structure of
      joint geometric and photometric transformations for both grayscale and color
      images. The image registration is formulated as a nonlinear least squares
      problem. In our method, the geometric and photometric transformations are jointly
      parameterized by their corresponding Lie algebras. Based on this parameterization
      approach, the second-order approximation strategy of ESM is employed to optimize
      the joint geometric and photometric parameters. The error function in the
      nonlinear least squares problem is approximated by a second-order Taylor
      expansion with respect to joint geometric and photometric parameters without
      computing the Hessian matrix. For further efficiency, independent convergence
      criteria for geometric and photometric parameters are used in the iterative
      optimization process. The superiority of our proposed method over the previous
      methods, in terms of efficiency, accuracy, and robustness, is demonstrated
      through extensive experiments on synthetic and real data.

PMID- 30106727
TI  - Chaotic Sensing.
AB  - We propose a sparse imaging methodology called Chaotic Sensing (ChaoS) that
      enables the use of limited yet deterministic linear measurements through fractal
      sampling. A novel fractal in the discrete Fourier transform is introduced that
      always results in the artefacts being turbulent in nature. These chaotic
      artefacts have characteristics that are image independent, facilitating their
      removal through dampening (via image denoising) and obtaining the maximum
      likelihood solution. In contrast with existing methods, such as compressed
      sensing, the fractal sampling is based on digital periodic lines that form the
      basis of discrete projected views of the image without requiring additional
      transform domains. This allows the creation of finite iterative reconstruction
      schemes in recovering an image from its fractal sampling that is also new to
      discrete tomography. As a result, ChaoS supports linear measurement and
      optimisation strategies, while remaining capable of recovering a theoretically
      exact representation of the image. We apply the method to simulated and
      experimental limited magnetic resonance (MR) imaging data, where restrictions
      imposed by MR physics typically favour linear measurements for reducing
      acquisition time.

PMID- 30106728
TI  - Assessing Image Retrieval Quality at the First Glance.
AB  - Image retrieval has achieved remarkable improvements with the rapid progress on
      visual representation and indexing techniques. Given a query image, search
      engines are expected to retrieve relevant results in which the top-ranked short
      list is of most value to users. However, it is challenging to measure the
      retrieval quality on-the-fly without direct user feedbacks. In this paper, we aim
      at evaluating the quality of retrieval results at the first glance (i.e., with
      the top-ranked images). For each retrieval result, we compute a correlation based
      feature matrix that comprises of contextual information from the retrieval list,
      and then feed it into a convolutional neural network regression model for
      retrieval quality evaluation. In this proposed framework, multiple visual
      features are integrated together for robust representations. We optimize the
      output of this simpleyet- effective evaluation method to be consistent with
      Discounted Cumulative Gain (DCG), the intuitive measure for the quality of the
      top-ranked results. We evaluate our method in terms of prediction accuracy and
      consistency with the ground truth, and demonstrate its practicability in
      applications such as rank list selection and database image abundance analyses.

PMID- 30106729
TI  - A Deep Multi-Modal CNN for Multi-Instance Multi-Label Image Classification.
AB  - Deep convolutional neural networks (CNNs) have shown superior performance on the
      task of single-label image classification. However, the applicability of CNNs to
      multi-label images still remains an open problem, mainly because of two reasons.
      First, each image is usually treated as an inseparable entity and represented as
      one instance, which mixes the visual information corresponding to different
      labels. Second, the correlations amongst labels are often overlooked. To address
      these limitations, we propose a deep multi-modal CNN for multi-instance multi
      label image classification, called MMCNN-MIML. By combining CNNs with multi
      instance multi-label (MIML) learning, our model represents each image as a bag of
      instances for image classification and inherits the merits of both CNNs and MIML.
      In particular, MMCNN-MIML has three main appealing properties: 1) it can
      automatically generate instance representations for MIML by exploiting the
      architecture of CNNs; 2) it takes advantage of the label correlations by grouping
      labels in its later layers; and 3) it incorporates the textual context of label
      groups to generate multi-modal instances, which are effective in discriminating
      visually similar objects belonging to different groups. Empirical studies on
      several benchmark multi-label image data sets show that MMCNN-MIML significantly
      outperforms the state-of-the-art baselines on multi-label image classification
      tasks.

PMID- 30106730
TI  - Efficient Correlation Tracking via Center-Biased Spatial Regularization.
AB  - Correlation filters (CFs) have been applied to visual tracking with success
      providing excellent performance in terms of accuracy and efficiency. The
      underlying periodic assumption of the training samples results in their great
      efficiency when using the fast Fourier transform (FFT), yet it also brings
      unwanted boundary effects. To address this issue, the recently proposed spatially
      regularized discriminative CF (SRDCF) method introduces a Gaussian weight
      function to regularize the learning filter, yielding favorable performances in
      accuracy but high computational complexity because the objective of the SRDCF
      cannot achieve a closed solution via the FFT. Motivated by SRDCF, we present an
      efficient and effective CF-based tracker using center-biased constraint weights
      (CBCWs), which improve simultaneously speed and accuracy. Specifically, we first
      construct a CBCW function by exploiting the symmetry of the Fourier transform.
      The values of the constraint weights are real in both time and frequency domains,
      so that the optimization can be directly solved in the frequency domain without
      any data transformation, thereby greatly reducing its computational complexity.
      Moreover, according to the average peak-tocorrelation energy value of the CF
      response, we propose an efficient and effective filter update strategy to handle
      occlusions during tracking. Extensive experiments on the OTB-2013, OTB- 2015, and
      VOT2016 benchmarks demonstrate that the proposed tracker significantly
      outperforms the baseline SRDCF in terms of accuracy and efficiency. Moreover, the
      proposed method performs favorably against 16 other representative state-of-the
      art methods regarding robustness and success rate.

PMID- 30106731
TI  - Attention CoupleNet: Fully Convolutional Attention Coupling Network for Object
      Detection.
AB  - The field of object detection has made great progress in recent years. Most of
      these improvements are derived from using a more sophisticated convolutional
      neural network. However, in the case of humans, the attention mechanism, global
      structure information, and local details of objects all play an important role
      for detecting an object. In this paper, we propose a novel fully convolutional
      network, named as Attention CoupleNet, to incorporate the attention-related
      information and global and local information of objects to improve the detection
      performance. Specifically, we first design a cascade attention structure to
      perceive the global scene of the image and generate class-agnostic attention
      maps. Then the attention maps are encoded into the network to acquire object
      aware features. Next, we propose a unique fully convolutional coupling structure
      to couple global structure and local parts of the object to further formulate a
      discriminative feature representation. To fully explore the global and local
      properties, we also design different coupling strategies and normalization ways
      to make full use of the complementary advantages between the global and local
      information. Extensive experiments demonstrate the effectiveness of our approach.
      We achieve state-of-the-art results on all three challenging data sets, i.e., a
      mAP of 85.7% on VOC07, 84.3% on VOC12, and 35.4% on COCO. Codes are publicly
      available at https://github.com/tshizys/CoupleNet.

PMID- 30106732
TI  - Modeling the Perceptual Quality of Immersive Images Rendered on Head Mounted
      Displays: Resolution and Compression.
AB  - We develop a model that expresses the joint impact of spatial resolution s and
      JPEG compression quality factor qf on immersive image quality. The model is
      expressed as the product of optimized exponential functions of these factors. The
      model is tested on a subjective database of immersive image contents rendered on
      a head mounted display (HMD). High Pearson correlation and Spearman correlation
      (> 0.95) and small relative root mean squared error (< 5.6%) are achieved between
      the model predictions and the subjective quality judgements. The immersive ground
      truth images along with the rest of the database are made available for future
      research and comparisons.

PMID- 30106733
TI  - SolarView: Low Distortion Radial Embeddings with a Focus.
AB  - We propose a novel type of low distortion radial embedding which focuses on one
      specific entity and its closest neighbors. Our embedding preserves near-exact
      distances to the focus entity and aims to minimize distortion between the other
      entities. We present an interactive exploration tool SolarView which places the
      focus entity at the center of a "solar system" and embeds its neighbors guided by
      concentric circles. SolarView provides an implementation of our novel embedding
      and several state-of-the-art dimensionality reduction and embedding techniques,
      which we adapted to our setting in various ways. We experimentally evaluated our
      embedding and compared it to these state-of-the-art techniques. The results show
      that our embedding competes with these techniques and achieves low distortion in
      practice. Our method performs particularly well when the visualization, and hence
      the embedding, adheres to the solar system design principle of our application.
      Nonetheless - as with all dimensionality reduction techniques - the distortion
      may be high. We leverage interaction techniques to give clear visual cues that
      allow users to accurately judge distortion. We illustrate the use of SolarView by
      exploring the high-dimensional metric space of bibliographic entity similarities.

PMID- 30106734
TI  - Mesh Denoising Guided by Patch Normal Co-filtering via Kernel Low-rank Recovery.
AB  - Mesh denoising is a classical, yet not well-solved problem in digital geometry
      processing. The challenge arises from noise removal with the minimal disturbance
      of surface intrinsic properties (e.g., sharp features and shallow details). We
      propose a new patch normal co-filter (PcFilter) for mesh denoising. It is
      inspired by the geometry statistics which show that surface patches with similar
      intrinsic properties exist on the underlying surface of a noisy mesh. We model
      the PcFilter as a low-rank matrix recovery problem of similar-patch
      collaboration, aiming at removing different levels of noise, yet preserving
      various surface features. We generalize our model to pursue the low-rank matrix
      recovery in the kernel space for handling the nonlinear structure contained in
      the data. By making use of the block coordinate descent minimization and the
      specifics of a proximal based coordinate descent method, we optimize the
      nonlinear and nonconvex objective function efficiently. The detailed quantitative
      and qualitative results on synthetic and real data show that the PcFilter
      competes favorably with the state-of-the-art methods in surface accuracy and
      noise-robustness.

PMID- 30106735
TI  - Camera-Based Mirror Visual Feedback: Potential to Improve Motor Preparation in
      Stroke Patients.
AB  - Mirror visual feedback (MVF) is used widely for motor recovery after stroke, but
      an optimal training setup and systematic procedure are lacking. New optimization
      strategies have been proposed, one of which is a camera technique. We
      investigated the effects of a camera-based MVF setup on motor function and motor
      processes upstream for upper-limb rehabilitation. Seventy-nine stroke patients
      were assigned randomly to the MVF group (MG; ${N} = {38}$ ) or conventional group
      (CG; ${N} = {41}$ ), which, respectively, received camera-based MVF and dosage
      equivalent physiotherapy or/and occupational therapy for 1 h/day and five
      days/week for four weeks. Two clinical scales were used to quantify the effect of
      the intervention methods: the Fugl-Meyer assessment-upper limb (FMA-UL) subscale
      and Barthel index. The hand laterality task was used to evaluate the ability of
      mental rotation, including the reaction time and accuracy. All measurements were
      improved significantly for both groups following intervention. FMA-UL was
      improved significantly in the MG compared with that in the CG. In lateralization
      tasks, the RT of the MG was significantly shorter than that of the CG at the
      endpoint. For all patients, judgments for the affected side were significantly
      slower and less accurate than for the less-affected side. Subgroup analyses
      suggested greater benefits of motor function, the activities of daily life, and
      mental rotation were achieved in subacute patients after MVF. A trend toward
      greater improvements in motor function for patients with severe-moderate motor
      impairment and patients with right-hemisphere damage were also revealed. Camera
      based MVF has improved the motor function and ability of mental rotation for
      stroke patients, especially for patients in the subacute stage, which indicates
      the potential to improve motor preparation. Further studies might combine mental
      rotation with electroencephalography to investigate the neuro-mechanism of MVF.

PMID- 30106736
TI  - Wrist Robot-assisted Rehabilitation Treatment in Subacute and Chronic Stroke
      Patients: from Distal to Proximal Motor Recovery.
AB  - In this study, the recovery of proximal and distal segments in stroke patients
      who received distal training alone was investigated. Forty (20 subacute and 20
      chronic) stroke patients were recruited to perform wrist robot-assisted
      rehabilitation training. The upper extremity, shoulder-elbow and wrist
      subsections of the Fugl-Meyer Assessment Scale were used to assess the motor
      recovery of distal and proximal segments. In addition, the Modified Ashworth
      Scale, the Motricity Index and the Box & Block test were used as clinical outcome
      measures together with kinematic parameters to evaluate the effects of the
      training. Significant increases in the wrist and shoulder-elbow subsections of
      the Fugl-Meyer Assessment Scale, Motricity Index and Box & Block test were found
      in both groups. Average changes in shoulder-elbow and upper extremity subsections
      of the Fugl-Meyer Assessment Scale in the subacute group (6.10 +/- 6.60 and 15.65
      +/- 14.04) were significantly higher (p < 0.05) than those in the chronic group
      (2.30 +/- 2.76 and 6.60 +/- 4.64). In addition, significant increases in the
      movement velocity, movement smoothness and movement quality were observed in the
      subacute group. Our findings provide evidence that following a robot-assisted
      rehabilitation treatment there is a distal-to-proximal generalization in subacute
      stroke patients.

PMID- 30106737
TI  - Impedance and Magnetohydrodynamic Measurements for Label Free Detection and
      Differentiation of E. Coli and S. Aureus Using Magnetic Nanoparticles.
AB  - In this paper, we used the distinguishable surface charge and mass of different
      bacterial strains for label free detection and differentiation of pathogen
      through impedance and magnetohydrodynamic (MHD) analysis. For the isolation of
      Escherichia coli and Staphylococcus aureus, functionalized magnetic nanoparticles
      (MNPs) were used. The proposed method is aimed at minimizing extensive chemical
      preparation and labor intensive conventional microbiological processing thereby
      reducing the detection time. Pathogens isolated from broth cultures using the
      MNPs were subjected to impedance rate measurement through an arduino-based
      automated impedance sensor along with differentiation on the basis of Larmor's
      motion through the MHD approach. The proposed method evidently reports that the
      two bacterial species bind differently to the MNPs giving appreciable variation
      in the impedance rate increment for a dc electric field of 250V/m. In addition to
      this, cross-field drift through 171.4 V/m electric field and a normal magnetic
      field of 500 Gauss led to lump formation in S. aureus but had no such effect on
      E. coli. The mobility analysis of the two species of bacteria was also carried
      out by observing the gyration of bacteria through naked eyes. The mobility of
      lumped bodies of S. aureus was of the order 10-10 m2/V sec; whereas for dispersed
      E. coli, it was 10-08 m2/V sec.

PMID- 30106738
TI  - Dual-layer Strengthened Collaborative Topic Regression Modeling for Predicting
      Drug Sensitivity.
AB  - An effective way to facilitate the development of modern oncology precision
      medicine is the systematical analysis of the known drug sensitivities that have
      emerged in recent years. Meanwhile, the screening of drug response in cancer cell
      lines provides an estimable genomic and pharmacological data towards high
      accuracy prediction. Existing works primarily utilize genomic or functional
      genomic features to classify or regress the drug response. Here in this work, by
      the migration and extension of the conventional merchandise recommendation
      methods, we introduce an innovation model on accurate drug sensitivity prediction
      by using dual-layer strengthened collaborative topic regression (DS-CTR), which
      incorporates not only the graphic model to jointly learn drugs and cell lines
      feature from pharmacogenomics data but also drug and cell line similarity network
      model to strengthen the correlation of the prediction results. Using Genomics of
      Drug Sensitivity in Cancer project (GDSC) as benchmark datasets, the 5-fold cross
      validation experiment demonstrates that DS-CTR model significantly improves drug
      response prediction performance compared with four categories of state-of-the-art
      algorithms as for both Receiver Operator Curve (ROC) and the Area Under Receiver
      Operator Curve (AUC). By uncovering the unknown cell-drug associations with
      advanced literature evidences, our novel model DS-CTR is validated and supported.
      The model also provides the possibility to make the discovery of new anti-cancer
      therapeutics in the preclinical trials cheaper and faster.

PMID- 30106739
TI  - Extension of Partial Gene Transcripts by Iterative Mapping of RNA-Seq Raw Reads.
AB  - Many non-model organisms lack reference genomes and the sequencing and de novo
      assembly of an organism's transcriptome is an affordable means by which to
      characterize the coding component of its genome. Despite the advances that have
      made this possible, assembling a transcriptome without a known reference usually
      results in a collection of full-length and partial gene transcripts. The
      downstream analysis of genes represented as partial transcripts then often
      requires further experimental work in the laboratory in order to obtain full-
      length sequences. We have explored whether partial transcripts, encoding genes of
      interest present in de novo assembled transcriptomes of a model and non-model
      insect species, could be further extended by iterative mapping against the raw
      transcriptome sequencing reads. Partial sequences encoding cytochrome P450s and
      carboxyl/cholinesterase were used in this analysis because they are large
      multigene families and exhibit significant variation in expression. We present an
      effective method to improve the continuity of partial transcripts in silico that,
      in the absence of a reference genome, maybe a quick and cost-effective
      alternative to their extension by laboratory experimentation. Our approach
      resulted in the successful extension of incompletely assembled transcripts, often
      to full length. We experimentally validated these results ?textit{in silico} and
      using real-time PCR and sequencing.

PMID- 30106740
TI  - A Tactile Computer Mouse for the Display of Surface Material Properties.
AB  - We present a novel input/output device to display the tactile properties of
      surface materials. The proposed Tactile Computer Mouse (TCM) is equipped with a
      series of actuators that can create perceptually relevant tactile cues to a user.
      The display capabilities of our TCM match the major tactile dimensions in human
      surface material perception, namely, hardness, friction, warmth, microscopic
      roughness, and macroscopic roughness. The TCM also preserves necessary
      interaction capabilities of a typical computer mouse. In addition to the TCM
      design, we introduce data acquisition procedures and concepts that are necessary
      to derive a parametric representation of a surface material and further
      demonstrate the corresponding rendering approach on the TCM. We conducted
      subjective experiments to determine tactile property ratings of real materials,
      perceived property ratings using the TCM, and how precisely subjects match the
      real materials to corresponding virtual material representations using the TCM in
      the absence of visual and audible clues. Our experimental results show that our
      TCM successfully displays the five fundamental tactile dimensions and that the
      twenty participants were able to perceive the TCM-produced virtual surface
      material tactile sensations with a recognition rate of 89.6% for ten different
      materials.

PMID- 30106741
TI  - Tactile Display Design for Flight Envelope Protection and Situational Awareness.
AB  - Spatial disorientation and visual channel saturation are defined as critical
      situations encountered by military pilots. Such subjects are interesting research
      areas likely to create innovative systems able to surmount obstacles of this
      kind. The integration of new stimulation techniques (sensory substitute, adjunct
      for visual and audio feedback) may be considered to make the visual channel
      better. This contribution may help in integrating tactile stimulation to improve
      or substitute the visual channel. It may also help to better interpret the
      spatial disorientation awareness signals and the vestibulo-ocular response
      limitations. The innovation of the proposed approach translates in: (i) the
      development of the PI-Inverse dynamics controller to provide a time delay
      reduction of the low cost tactile actuator, and thus, high-performance tactile
      system; (ii) an approach based on fuzzy logic controller (FLC) is being used in
      order to translate the turn rate angle, the flight path climb angle and the
      warning messages into tactile signal features instead of a conventional approach
      based on direct coding of the pitch and bank angles; and (iii) the consideration
      of the flight envelope. The fuzzy set translation of flight parameters into
      tactile signals is also a pragmatic and useful way to design the system.

PMID- 30106742
TI  - Self-Organizing Neuroevolution for Solving Carpool Service Problem With Dynamic
      Capacity to Alternate Matches.
AB  - Traffic congestion often incurs environmental problems. One of the most effective
      ways to mitigate this is carpooling transportation, which substantially reduces
      automobile demands. Due to the popularization of smartphones and mobile
      applications, a carpool service can be conveniently accessed via the intelligent
      carpool system. In this system, the service optimization required to
      intelligently and adaptively distribute the carpool participant resources is
      called the carpool service problem (CSP). Several previous studies have examined
      viable and preliminary solutions to the CSP by using exact and metaheuristic
      optimization approaches. For CSP-solving, evolutionary computation (e.g.,
      metaheuristics) is a more promising option in comparison to exact-type
      approaches. However, all the previous state-of-the-art approaches use pure
      optimization to solve the CSP. In this paper, we employ the framework of
      neuroevolution to propose the self-organizing map-based neuroevolution (SOMNE)
      solver by which the SOM-like network represents the abstract CSP solution and is
      well-trained by using neural learning and evolutionary mechanism. The
      experimental section of this paper investigates the comparisons and analyses of
      two objective functions of the CSP and demonstrates that the proposed SOMNE
      solver achieves superior results when compared against those the other approaches
      produce, especially in regard to the optimization of the primary objective
      functions of the CSP. Finally, the visual results of the SOM are illustrated to
      show the effectiveness and efficiency of the evolutionary neural learning
      process.

PMID- 30106743
TI  - Category-Based Deep CCA for Fine-Grained Venue Discovery From Multimodal Data.
AB  - In this work, travel destinations and business locations are taken as venues.
      Discovering a venue by a photograph is very important for visual context-aware
      applications. Unfortunately, few efforts paid attention to complicated real
      images such as venue photographs generated by users. Our goal is fine-grained
      venue discovery from heterogeneous social multimodal data. To this end, we
      propose a novel deep learning model, category-based deep canonical correlation
      analysis. Given a photograph as input, this model performs: 1) exact venue search
      (find the venue where the photograph was taken) and 2) group venue search (find
      relevant venues that have the same category as the photograph), by the cross
      modal correlation between the input photograph and textual description of venues.
      In this model, data in different modalities are projected to a same space via
      deep networks. Pairwise correlation (between different modality data from the
      same venue) for exact venue search and category-based correlation (between
      different modality data from different venues with the same category) for group
      venue search are jointly optimized. Because a photograph cannot fully reflect
      rich text description of a venue, the number of photographs per venue in the
      training phase is increased to capture more aspects of a venue. We build a new
      venue-aware multimodal data set by integrating Wikipedia featured articles and
      Foursquare venue photographs. Experimental results on this data set confirm the
      feasibility of the proposed method. Moreover, the evaluation over another
      publicly available data set confirms that the proposed method outperforms state
      of the arts for cross-modal retrieval between image and text.

PMID- 30106744
TI  - Finger-to-Heart(F2H): Authentication for Wireless Implantable Medical Devices.
AB  - Any proposal to provide security for Implantable Medical Devices (IMDs), such as
      cardiac pacemakers and defibrillators, has to achieve a trade-off between
      security and accessibility for doctors to gain access to an IMD, especially in an
      emergency scenario. In this paper, we propose a Finger-to-Heart (F2H) IMD
      authentication scheme to address this trade-off between security and
      accessibility. This scheme utilizes a patient's fingerprint to perform
      authentication for gaining access to the IMD. Doctors can gain access to the IMD
      and perform emergency treatment by scanning the patient's finger tip instead of
      asking the patient for passwords/security tokens thereby achieving the necessary
      trade-off. In the scheme, an improved Minutia Cylinder-Code (MCC) based
      fingerprint authentication algorithm is proposed for the IMD by reducing the
      length of each feature vector and the number of query feature vectors.
      Experimental results show that the improved fingerprint authentication algorithm
      significantly reduces both the size of messages in transmission and computational
      overheads in the device, and thus can be utilized to secure the IMD. Compared to
      existing electrocardiogram signal-based security schemes, the F2H scheme does not
      require the IMD to capture or process biometric traits in every access attempt
      since a fingerprint template is generated and stored in the IMD beforehand. As a
      result, the scarce resources in the IMD are conserved, making the scheme
      sustainable as well as energy efficient.

PMID- 30106745
TI  - IMU-Based Classification of Parkinson's Disease From Gait: A Sensitivity Analysis
      on Sensor Location and Feature Selection.
AB  - Inertial measurement units (IMUs) have a long-lasting popularity in a variety of
      industrial applications from navigation systems to guidance and robotics. Their
      use in clinical practice is now becoming more common, thanks to miniaturization
      and the ability to integrate on-board computational and decision-support
      features. IMU-based gait analysis is a paradigm of this evolving process, and in
      this study its use for the assessment of Parkinson's disease (PD) is
      comprehensively analyzed. Data coming from 25 individuals with different levels
      of PD symptoms severity and an equal number of age-matched healthy individuals
      were included into a set of 6 different machine learning (ML) techniques,
      processing 18 different configurations of gait parameters taken from 8 IMU
      sensors. Classification accuracy was calculated for each configuration and ML
      technique, adding two meta-classifiers based on the results obtained from all
      individual techniques through majority of voting, with two different weighting
      schemes. Average classification accuracy ranged between 63% and 80% among
      classifiers and increased up to 96% for one meta-classifier configuration.
      Configurations based on a statistical preselection process showed the highest
      average classification accuracy. When reducing the number of sensors, features
      based on the joint range of motion were more accurate than those based on spatio
      temporal parameters. In particular, best results were obtained with the knee
      range of motion, calculated with four IMUs, placed bilaterally. The obtained
      findings provide data-driven evidence on which combination of sensor
      configurations and classification methods to be used during IMU-based gait
      analysis to grade the severity level of PD.

PMID- 30106746
TI  - $Hinfinity Synchronization of Networked Master-Slave Oscillators With Delayed
      Position Data: The Positive Effects of Network-Induced Delays.
AB  - This paper is concerned with Hinfinity synchronization of coupled oscillators in
      a master-slave framework, in which the oscillators cannot be stabilized by
      nondelayed sampled position data, but can be stabilized by sampled position data
      with delays restricted by nonzero lower bounds and upper bounds. A configuration
      of networked master-slave oscillators with a remote controller is first
      constructed. Then the positive effects of delays on master-slave synchronization
      are investigated. Some delay-dependent Hinfinity synchronization criteria are
      derived by constructing augmented discretized Lyapunov-Krasovskii functionals for
      determinate sampling and stochastic sampling, respectively. The controller can be
      designed by solving a set of linear matrix inequalities. Finally, two numerical
      examples are given to verify the theoretical results. It is shown that the
      maximum allowable sampling period in the case of stochastic sampling is larger
      than the one in the case of determinate sampling. Stochastic sampling can also
      provide a tradeoff between network-induced delays and the sampling periods,
      enhancing the master-slave synchronization performance.

PMID- 30106747
TI  - Fuzzy Broad Learning System: A Novel Neuro-Fuzzy Model for Regression and
      Classification.
AB  - A novel neuro-fuzzy model named fuzzy broad learning system (BLS) is proposed by
      merging the Takagi-Sugeno (TS) fuzzy system into BLS. The fuzzy BLS replaces the
      feature nodes of BLS with a group of TS fuzzy subsystems, and the input data are
      processed by each of them. Instead of aggregating the outputs of fuzzy rules
      produced by every fuzzy subsystem into one value immediately, all of them are
      sent to the enhancement layer for further nonlinear transformation to preserve
      the characteristic of inputs. The defuzzification outputs of all fuzzy subsystem
      and the outputs of enhancement layer are combined together to obtain the model
      output. The k-means method is employed to determine the centers of Gaussian
      membership functions in antecedent part and the number of fuzzy rules. The
      parameters that need to be calculated in a fuzzy BLS are the weights connecting
      the outputs of enhancement layer to model output and the randomly initialized
      coefficients of polynomials in consequent part in fuzzy subsystems, which can be
      calculated analytically. Therefore, fuzzy BLS retains the fast computational
      nature of BLS. The proposed fuzzy BLS is evaluated by some popular benchmarks for
      regression and classification, and compared with some state-of-the-art nonfuzzy
      and neuro-fuzzy approaches. The results indicate that fuzzy BLS outperforms other
      models involved. Moreover, fuzzy BLS shows advantages over neuro-fuzzy models
      regarding to the number of fuzzy rules and training time, which can ease the
      problem of rule explosion to some extent.

PMID- 30106748
TI  - A Non-Monte-Carlo Parameter-Free Learning Automata Scheme Based on Two Categories
      of Statistics.
AB  - Learning automata (LA), which intellectually explores its optimal state by
      interacting with an external environment continuously, is encountered widely in
      artificial intelligence. In the evaluation of LA, it has always been a key issue
      how to tradeoff between ''accuracy'' and ''speed,'' which substantially touches
      on parameter tuning. A latest issue in the design of LA methodology involves
      bearing a parameter-free property, thus removing the tremendous expenses brought
      by parameter tuning. Nevertheless, the currently existing parameter-free LA
      schemes generally maintain a Monte-Carlo technique, which helps avoid the tuning
      process at the cost of more computations. This paper examines a new measurement
      of parameter-free LA schemes based on statistics which overcome the difficulties
      found in other counterparts. Specifically, it has innovatively disengaged from
      the dependance on Monte-Carlo methods. Of greater significance, the learning
      mechanisms operating in the common stationary environments are likewise extended
      to the nonstationary environments. Simulations confirm the effectiveness and
      efficiency of the proposed algorithm, especially its low computation consumption
      as well as the strong tracking capability to abrupt environmental changes.

PMID- 30106749
TI  - Recurrent Neural Network for Kinematic Control of Redundant Manipulators With
      Periodic Input Disturbance and Physical Constraints.
AB  - Input disturbances and physical constraints are important issues in the kinematic
      control of redundant manipulators. In this paper, we propose a novel recurrent
      neural network to simultaneously address the periodic input disturbance, joint
      angle constraint, and joint velocity constraint, and optimize a general quadratic
      performance index. The proposed recurrent neural network applies to both
      regulation and tracking tasks. Theoretical analysis shows that, with the proposed
      neural network, the end-effector tracking and regulation errors asymptotically
      converge to zero in the presence of both input disturbance and the two
      constraints. Simulation examples and comparisons with an existing controller are
      also presented to validate the effectiveness and superiority of the proposed
      controller.

PMID- 30106750
TI  - Physical activity and physical fitness as protective factors of adolescent
      health.
AB  - Objective This quantitative correlational design study aimed to examine the
      variation in adolescent health and lifestyle characteristics across self-reported
      physical activity (PA) and physical fitness (PF) levels. Methods Data were
      collected from 422 students (50.2% males) (16.33 SD = 1.66 y/o) attending a high
      school. An online questionnaire was used to gather data on the following
      characteristics: self-reported well-being, overall life satisfaction, depression
      (including self-harm and suicidal ideation), perceived health status, eating
      disorders, sleepiness, substance use (alcohol, tobacco and illicit drug use),
      body mass index, PA participation and PF levels. Results Of the participants,
      42.4% reported at least 5 days of PA a week for 60 min per day. These high active
      individuals had significantly better well-being, health status, life
      satisfaction, PF and consumed fewer alcohol beverages. High PA and better PF
      inversely correlated with depression. Conclusions It seems that high PA and
      better PF have a positive impact on adolescent perceived health, health-risk
      behaviors and mental health. Increased levels of PA can play a vital role in the
      primary care, prevention of health risks and in adolescent health promotion.
      Accordingly, educational institutions are an excellent setting to promote and
      provide sport facilities and encourage students to be more physically active.

PMID- 30106751
TI  - Overweight or obesity and related lifestyle and psychosocial factors among
      adolescents in Brunei Darussalam.
AB  - This study aimed to assess overweight and obesity and associated factors in
      school-going adolescents in Brunei Darussalam. The sample included 2599 school
      going adolescents that responded to the Global School-based Student Health Survey
      (mean age 14.7 years, SD = 1.4). Body weight status was assessed based on self
      reported height and weight and the international child body mass index standards.
      The relationship between lifestyle factors, including physical activity and
      dietary behaviour, and overweight or obesity were assessed using logistic
      regression analyses. Results indicate a prevalence of overweight or obesity of
      35.1% and obesity of 17.3%. In multivariable regression analysis, bullying
      victimisation was positively and frequent fast food consumption, having
      experienced hunger and meeting physical activity recommendations were negatively
      associated with overweight or obesity. High prevalence rates of overweight or
      obesity were found and several risk factors identified, which can assist in
      guiding interventions.

PMID- 30106753
TI  - A novel hedgehog inhibitor for the treatment of hematological malignancies.
AB  - The hedgehog-smoothened (HH/SMO) pathway has been proposed as a potential
      therapeutic target for hematological malignancies. Our previous studies designed
      a series of HH inhibitors with novel scaffolds distinctive from vismodegib, the
      first Food and Drug Administration-approved HH inhibitor for the treatment of
      basal-cell carcinoma and medulloblastoma. In the present study, we evaluated
      these HH inhibitors against blood cancers and found that HH78 displayed potent
      activity in suppressing the HH signaling pathway. HH78 competitively bound to SMO
      and suppressed the transcriptional activity of GLI by the luciferase reporter
      gene assay and the measurement of HH/SMO-downregulated genes, including cyclin
      D2, cyclin E, PTCH1, PTCH2, and GLI. HH78 at low micromolar concentrations
      induced significant cancer cell apoptosis showed by increased caspase-3
      activation, annexin V-staining and downregulated prosurvival proteins, including
      c-Myc, Bcl-2, Mcl-1, and Bcl-xL. In contrast, vismodegib did not show any effects
      on these apoptotic events. HH78 also suppressed the activation of the AKT/mTOR
      pathway, which cross-talks with the HH/SMO pathway. Finally, HH78 inhibited the
      growth of human leukemia K562 in nude mice xenografts with no overt toxicity.
      Collectively, the present study identified a novel HH inhibitor with great
      potential for the treatment of hematological malignancies.

PMID- 30106754
TI  - Birth in High Infant Mortality States and Dementia Risk in a Cohort of Elderly
      African American and White Health Care Members.
AB  - IMPORTANCE: Birth in areas with high infant mortality rates (IMRs) has been
      linked to worse long-term health outcomes, yet it is completely unknown if it
      impacts dementia risk. METHODS: In total 6268 health care members were followed
      for dementia diagnosis from 1996 to 2015. Birth state IMRs from 1928 were ranked
      into quartile (worst IMRs quartile range, whites: 69 to 129 deaths/1000 live
      births, Non-whites: 129 to 277 deaths/1000 live births). Cox proportional hazard
      models estimated the dementia risk associated with birth state IMR quartile
      adjusting for demographics and lifecourse health indicators. RESULTS: Compared
      with whites born outside of states in the worst IMR quartile, African Americans
      born in states in the worst IMR quartile had 92% increased dementia risk
      (HR=1.92; 95% CI: 1.42, 2.59), and African Americans born outside those states
      had 36% increased risk (HR=1.36; 95% CI: 1.20, 1.53). There was no association
      between birth state IMR and dementia risk among whites. CONCLUSIONS: Birth in
      states with the highest rates of infant mortality was associated with elevated
      dementia risk among African Americans but not whites. The large absolute
      difference in IMRs likely reflects harsher early childhood conditions experienced
      by African Americans. These findings suggest that childhood conditions may play a
      role in racial disparities in dementia rates.

PMID- 30106755
TI  - Functional Activity and Neuropsychiatric Symptoms in Normal Aging and Mild
      Cognitive Impairment: The Mayo Clinic Study of Aging.

PMID- 30106756
TI  - The Effect of Changing the Amyloid beta42 Cut-off of Cerebrospinal Fluid
      Biomarkers on Alzheimer Disease Diagnosis in a Memory Clinic Population in
      Norway.

PMID- 30106752
TI  - The vimentin intermediate filament network restrains regulatory T cell
      suppression of graft-versus-host disease.
AB  - Regulatory T cells (Tregs) are critical for maintaining immune homeostasis.
      However, current Treg immunotherapies do not optimally treat inflammatory
      diseases in patients. Understanding the cellular processes that control Treg
      function may allow for the augmentation of therapeutic efficacy. In contrast to
      activated conventional T cells, in which protein kinase C-theta (PKC-theta)
      localizes to the contact point between T cells and antigen-presenting cells, in
      human and mouse Tregs, PKC-theta localizes to the opposite end of the cell in the
      distal pole complex (DPC). Here, using a phosphoproteomic screen, we identified
      the intermediate filament vimentin as a PKC-theta phospho target and show that
      vimentin forms a DPC superstructure on which PKC-theta accumulates. Treatment of
      mouse Tregs with either a clinically relevant PKC-theta inhibitor or vimentin
      siRNA disrupted vimentin and enhanced Treg metabolic and suppressive activity.
      Moreover, vimentin-disrupted mouse Tregs were significantly better than controls
      at suppressing alloreactive T cell priming in graft-versus-host disease (GVHD)
      and GVHD lethality, using a complete MHC-mismatch mouse model of acute GVHD
      (C57BL/6 donor into BALB/c host). Interestingly, vimentin disruption augmented
      the suppressor function of PKC-theta-deficient mouse Tregs. This suggests that
      enhanced Treg activity after PKC-theta inhibition is secondary to effects on
      vimentin, not just PKC-theta kinase activity inhibition. Our data demonstrate
      that vimentin is a key metabolic and functional controller of Treg activity and
      provide proof of principle that disruption of vimentin is a feasible,
      translationally relevant method to enhance Treg potency.

PMID- 30106757
TI  - Behavioral Variant Frontotemporal Dementia-like Syndrome With Novel Heterozygous
      TREM2 Frameshift Mutation.

PMID- 30106758
TI  - Lymphocyte-to-Monocyte Ratio May Serve as a Better Prognostic Indicator Than
      Tumor-associated Macrophages in DLBCL Treated With Rituximab.
AB  - There are multiple prognostic indicators for diffuse large B-cell lymphoma
      (DLBCL) including the international prognostic index (IPI), and gene expression
      profiling (GEP) to classify the disease into germinal center B-cell and activated
      B-cell subtypes, the latter harboring inferior prognosis. More recently, tumor
      associated macrophages (TAM) and lymphocyte-to-monocyte ratio (LMR) were found to
      have prognostic implications in DLBCL. However, consensus is yet to be reached in
      terms of the significance of each. In this study, we evaluated the prognostic
      value of TAM as assessed by CD163 or CD68 positivity by immunohistochemistry on
      tissue biopsies and LMR was calculated from peripheral blood differential, with
      focus on the inclusion of rituximab as a treatment modality. The number of CD68
      positive cells in the tumor microenvironment did not exhibit significant
      prognostic value, whereas higher number of CD163-positive cells was associated
      with inferior overall survival in patients treated with chemotherapy alone. This
      effect was no longer evident in patients treated with rituximab containing
      chemoimmunotherapy. In contrast, the prognostic significance of LMR on survival
      was more persistent regardless of treatment. There was no association between LMR
      and the number of CD163-positive cells. Our results suggest that LMR is the more
      easily and widely available prognostic marker in this era of chemoimmunotherapy.
      Our finding supports previous literature that the effect of TAM can vary
      according to treatment. Interaction between rituximab and TAM warrant further
      scientific investigation for mechanistic insights into targeted therapeutics.

PMID- 30106759
TI  - Dynamic Prognostication in Critically Ill Cirrhotic Patients With Multiorgan
      Failure in ICUs in Europe and North America: A Multicenter Analysis.
AB  - OBJECTIVES: To evaluate the Chronic Liver Failure-Consortium Acute on Chronic
      Liver Failure score in acute on chronic liver failure patients admitted to ICUs
      from different global regions and compare discrimination ability with previously
      published scores. DESIGN: Retrospective pooled analysis. SETTING: Academic ICUs
      in Canada (Edmonton, Vancouver) and Europe (Paris, Barcelona, Chronic liver
      failure/Acute-on-Chronic Liver Failure in Cirrhosis [CANONIC] study). PATIENTS:
      Sample of analysis of 867 cirrhotic patients with acute on chronic liver failure
      admitted to ICU. Cumulative incidence functions of death were estimated by acute
      on chronic liver failure grade at admission and at day 3. Survival discrimination
      abilities of Chronic Liver Failure-Consortium Acute on Chronic Liver Failure,
      Model for End-Stage Liver Disease, Acute Physiology and Chronic Health Evaluation
      II, and Child-Turcotte-Pugh scores were compared. INTERVENTIONS: ICU admission
      for organ support. MEASUREMENTS AND MAIN RESULTS: At admission 169 subjects (19%)
      had acute on chronic liver failure 1, 302 (35%) acute on chronic liver failure 2,
      and 396 (46%) had acute on chronic liver failure 3 with 90-mortality rates of
      33%, 40%, and 74%, respectively (p < 0.001). At admission, Chronic Liver Failure
      Consortium Acute on Chronic Liver Failure demonstrated superior discrimination at
      90 days compared with Acute Physiology and Chronic Health Evaluation II (n = 532;
      concordance index 0.67 vs 0.62; p = 0.0027) and Child-Turcotte-Pugh (n = 666;
      0.68 vs 0.64; p = 0.0035), but not Model for End-Stage Liver Disease (n = 845;
      0.68 vs 0.67; p = 0.3). A Chronic Liver Failure-Consortium Acute on Chronic Liver
      Failure score greater than 70 at admission or on day 3 was associated with 90-day
      mortality rates of approximately 90%. Ninety-day mortality in grade 3 acute on
      chronic liver failure patients at admission who demonstrated improvement by day 3
      was 40% (vs 79% in patients who did not). CONCLUSIONS: The Chronic Liver Failure
      Consortium Acute on Chronic Liver Failure demonstrated better discrimination at
      day 28 and day 90 compared with Acute Physiology and Chronic Health Evaluation II
      and Child-Turcotte-Pugh. Patients who demonstrated clinical improvement post-ICU
      admission (e.g., acute on chronic liver failure 3 to 1 or 2) at day 3 had better
      outcomes than those who did not. In high-risk ICU patients (Chronic Liver Failure
      Consortium Acute on Chronic Liver Failure > 70), decisions regarding transition
      to palliation should be explored between patient families and the ICU providers
      after a short trial of therapy.

PMID- 30106760
TI  - Association of smoking with liver fibrosis and mortality in primary biliary
      cholangitis.
AB  - BACKGROUND: The outcome of primary biliary cholangitis (PBC) is affected by both
      genetic and environmental factors. OBJECTIVE: The aim of this study was to study
      the effect of smoking on liver histology and mortality in a genetically
      homogeneous population having PBC. PATIENTS AND METHODS: Smoking and drinking
      habits at diagnosis (based on standard criteria) were recorded in 171 Cretan
      patients with PBC (163 women). A total of 148 patients had a liver biopsy. Odds
      ratios were calculated with logistic regression analysis. Kaplan-Meier curves
      were used for mortality estimation. RESULTS: Smoking was associated with alcohol
      consumption of more than 20 g/day [adjusted odds ratio (AOR)=2.20, 95% CI: 1.029
      4.099], severe steatosis (AOR=5.31, 95% CI: 2.019-9.919), and fibrosis stage F3
      F4 (AOR=1.21, 95% CI: 1.015-3.031). Heavy smoking, years of passive smoking, and
      serious necroinflammatiomicronn were independent factors associated with advanced
      fibrosis after adjustment for sex, age, BMI, and alcohol consumption in
      multivariate analysis. For every pack-year increase in smoking intensity, there
      was a 3.2 times higher likelihood of advanced fibrosis (95% CI: 2.018-6.294).
      Increased mortality was found in smokers with advanced PBC. CONCLUSION: There is
      an association between smoking, whether active or passive, and advanced fibrosis
      in PBC. Mortality is increased in smokers with advanced disease at presentation.

PMID- 30106761
TI  - Soft-Tissue Infection Caused by Streptococcus anginosus After Intramucosal
      Hyaluronidase Injection: A Rare Complication Related to Dermal Filler Injection.

PMID- 30106762
TI  - Complications After Pelvic Arteriography in Patients With Pelvic Ring
      Disruptions.
AB  - INTRODUCTION: Pelvic angiography with transcatheter arterial embolization (TAE)
      is an established intervention for management of pelvic arterial hemorrhage. This
      study analyzes complication rates after angiography among patients with pelvic
      trauma treated in the context of a multidisciplinary institutional pelvic
      fracture protocol. METHODS: Retrospective analysis of prospectively collected
      data was conducted. Demographics, fracture type, embolization (ie, unilateral
      versus bilateral and selective versus nonselective), and complications (ie,
      pseudoaneurysm, renal failure, soft-tissue necrosis/infection, and anaphylactic
      reactions) were noted. RESULTS: Eighty-one patients with pelvic ring injuries
      underwent angiography from 2009 to 2013. Complications among 41 patients who
      underwent angiography with TAE were compared with a control group of 40 patients
      who underwent angiography without TAE. Eight of 41 patients with TAE had
      complications (19.5%) compared with 3 of 40 (7.5%) in the control group (P =
      0.19). The overall complication rate was 13.6%. CONCLUSION: The use of
      angiography with TAE as part of an institutional pelvic fracture protocol
      involves an acceptable rate of complications. LEVEL OF EVIDENCE: III.

PMID- 30106764
TI  - Reverse Shoulder Arthroplasty: Perioperative Considerations and Complications.

PMID- 30106763
TI  - Femoral Derotation Osteotomy in Adults for Version Abnormalities.
AB  - BACKGROUND: Version abnormalities of the femur can cause pain and hip joint
      damage due to impingement or instability. A retrospective clinical review was
      conducted on patients undergoing a subtrochanteric derotation osteotomy for
      either excessive anteversion or retroversion of the femur. METHODS: A total of 55
      derotation osteotomies were performed in 43 patients: 36 females and 7 males. The
      average age was 29 years (range, 14 to 59 years). The osteotomies were performed
      closed with an intramedullary saw. Fixation was performed with a variety of
      intramedullary nails. Twenty-nine percent of patients had a retroversion
      deformity (average, -9 degrees  of retroversion; range, +2 degrees  to -23
      degrees ) and 71% had excessive anteversion of the femur (average, +37 degrees 
      of anteversion; range, +22 degrees  to +53 degrees ). The etiology was
      posttraumatic in 5 patients (12%), diplegic cerebral palsy in 2 patients (5%),
      Prader-Willi syndrome in 1 patient (2%), and idiopathic in 35 patients (81%).
      Forty-nine percent underwent concomitant surgery with the index femoral
      derotation osteotomy, including hip arthroscopy in 40%, tibial derotation
      osteotomy in 13%, and a periacetabular osteotomy in 5%. Tibial osteotomies were
      performed to correct a compensatory excessive external tibial torsion that would
      be exacerbated in the correction of excessive femoral anteversion. RESULTS: No
      patient was lost to follow-up. Failures occurred in three hips in three patients
      (5%): two hip arthroplasties and one nonunion that healed after rerodding. There
      was one late infection treated successfully with implant removal and antibiotics
      with an excellent final clinical outcome. At an average follow-up of 6.5 years
      (range, 2 to 19.7 years), the modified Harris Hip Score improved by 29 points in
      the remaining 52 cases (P < 0.001, Wilcoxon signed-rank test). The results were
      rated as excellent in 75%, good in 23%, and fair in 2%. Subsequent surgery was
      required in 78% of hips, 91% of which were implant removals. CONCLUSIONS: A
      closed, subtrochanteric derotation osteotomy of the femur is a safe and effective
      procedure to treat either femoral retroversion or excessive anteversion.
      Excellent or good results were obtained in 93%, despite the need for subsequent
      implant removal in more than two-thirds of the patients.

PMID- 30106765
TI  - Operative Management of Degenerative Spondylolisthesis: A Critical Analysis
      Review.

PMID- 30106766
TI  - Inflammatory and Comorbid Features of Children Admitted to a PICU for Status
      Asthmaticus.
AB  - OBJECTIVES: To determine risk factors associated with admission to a PICU with or
      without endotracheal intubation for an asthma exacerbation. We hypothesized that
      children with critical and near-fatal asthma would have distinguishing clinical
      features but varying degrees of asthma severity and measures of type 2
      inflammation. DESIGN: Retrospective analysis of prospectively collected data of
      children with asthma recruited into outpatient asthma clinical research studies
      at Emory University between 2004 and 2015. SETTING: Large, free-standing academic
      quaternary care children's hospital in Atlanta, GA. PATIENTS: Children 6-18 years
      old with physician-diagnosed and confirmed asthma. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: A total of 579 children were analyzed with 170
      children (29.4%) being admitted to the PICU for an asthma exacerbation in their
      lifetime. Of these 170 children with a history of critical asthma, 24.1% were
      classified as having mild-to-moderate asthma, and 83 of 170 children (48.8%) had
      been intubated and experienced near-fatal asthma. Multiple logistic regression
      was used to identify risk factors associated with increased odds of PICU
      admission with or without endotracheal intubation. Hospitalization within the
      prior 12 months of survey (odds ratio, 8.19; 95% CI, 4.83-13.89), a history of
      pneumonia (odds ratio, 2.56; 95% CI, 1.52-4.29), having a designation of
      increased chronic asthma severity on high-dose inhaled corticosteroids (odds
      ratio, 2.76; 95% CI, 1.62-4.70), having a father with asthma (odds ratio, 2.15;
      95% CI, 1.23-3.76), living in a region with a higher burden of poverty (odds
      ratio, 1.28; 95% CI, 1.02-1.61), and being of black race (odds ratio, 2.01; 95%
      CI, 1.05-3.84) were all associated with increased odds of PICU admission with or
      without intubation. CONCLUSIONS: Our findings suggest that there are factors
      associated with critical and near-fatal asthma, distinct from the chronic asthma
      severity designations, that should be the focus of future investigation.

PMID- 30106769
TI  - Response to and.

PMID- 30106768
TI  - Letter to the Editor: Comments on the Ear and Hearing Ban on Certain Auditory
      Processing Disorder Articles Re: Moore, D. R. (2018) Editorial: Auditory
      Processing Disorder, Ear Hear, 39, 617-620.

PMID- 30106773
TI  - This Month in Anesthesiology.

PMID- 30106767
TI  - Hemolysis During Pediatric Extracorporeal Membrane Oxygenation: Associations With
      Circuitry, Complications, and Mortality.
AB  - OBJECTIVES: To describe factors associated with hemolysis during pediatric
      extracorporeal membrane oxygenation and the relationships between hemolysis,
      complications, and mortality. DESIGN: Secondary analysis of data collected
      prospectively by the Collaborative Pediatric Critical Care Research Network
      between December 2012 and September 2014. SETTING: Three Collaborative Pediatric
      Critical Care Research Network-affiliated hospitals. PATIENTS: Age less than 19
      years and treated with extracorporeal membrane oxygenation. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Hemolysis was defined based on peak plasma free
      hemoglobin levels during extracorporeal membrane oxygenation and categorized as
      none (< 0.001 g/L), mild (0.001 to < 0.5 g/L), moderate (0.5 to < 1.0 g/L), or
      severe (>= 1.0 g/L). Of 216 patients, four (1.9%) had no hemolysis, 67 (31.0%)
      had mild, 51 (23.6%) had moderate, and 94 (43.5%) had severe. On multivariable
      analysis, variables independently associated with higher daily plasma free
      hemoglobin concentration included the use of in-line hemofiltration or other
      continuous renal replacement therapy, higher hemoglobin concentration, higher
      total bilirubin concentration, lower mean heparin infusion dose, lower body
      weight, and lower platelet count. Using multivariable Cox modeling, daily plasma
      free hemoglobin was independently associated with development of renal failure
      during extracorporeal membrane oxygenation (defined as creatinine > 2 mg/dL [>
      176.8 MUmol/L] or use of in-line hemofiltration or continuous renal replacement
      therapy) (hazard ratio, 1.04; 95% CI, 1.02-1.06; p < 0.001), but not mortality
      (hazard ratio, 1.01; 95% CI, 0.99-1.04; p = 0.389). CONCLUSIONS: Hemolysis is
      common during pediatric extracorporeal membrane oxygenation. Hemolysis may
      contribute to the development of renal failure, and therapies used to manage
      renal failure such as in-line hemofiltration and other forms of continuous renal
      replacement therapy may contribute to hemolysis. Hemolysis was not associated
      with mortality after controlling for other factors. Monitoring for hemolysis
      should be a routine part of extracorporeal membrane oxygenation practice, and
      efforts to reduce hemolysis may improve patient care.

PMID- 30106775
TI  - Bypassing Poor Outcomes: Cardiac Surgery and Intraoperative Hypotension.

PMID- 30106777
TI  - Dr. Hezekiah Stratton, Brooklyn's Robin Hood Dentist-Anesthetist.

PMID- 30106778
TI  - Tintype and Chloroform Inhaler of Confederate Surgeon J. J. Chisolm, Not
      Chisholm.

PMID- 30106779
TI  - J. K. P. Pine Collars New York's Upstate Market on Nitrous Oxide Cylinders.

PMID- 30106770
TI  - Letter to the Editor: An Affront to Scientific Inquiry Re: Moore, D. R. (2018)
      Editorial: Auditory Processing Disorder, Ear Hear, 39, 617-620.

PMID- 30106781
TI  - Cherubic Rescues by H. E. Meeker, M.D.: Cocaine Prescription and Safety-pin
      Extraction.

PMID- 30106780
TI  - Harold Foster's Laughing Gas or Gags That Get Grins.

PMID- 30106782
TI  - Streams of Unconsciousness VI: General Anesthesia Reflected in Plutonic Rivers.

PMID- 30106783
TI  - Xenon Myocardial Protection in Cardiac Surgery: Effective around the Clock?

PMID- 30106785
TI  - Editorial Views and Policies.

PMID- 30106786
TI  - In Reply.

PMID- 30106784
TI  - In Reply.

PMID- 30106787
TI  - Clinical Decision Support Tools Need to Improve More Than Just Process Outcomes.

PMID- 30106788
TI  - The Curse of Dimensionality.

PMID- 30106789
TI  - In Reply.

PMID- 30106790
TI  - Health Locus of Control Is Associated With Physical Activity and Other Health
      Behaviors in Cardiac Patients.
AB  - PURPOSE: Physical inactivity, smoking, and excessive alcohol use are well
      recognized modifiable risk factors for cardiovascular disease (CVD), yet uptake
      of strategies to mitigate these poor health behaviors varies widely among
      patients with cardiovascular disease. Part of this variation may be explained by
      health locus of control (HLOC), defined as the extent to which individuals
      believe their health is a consequence of their own actions, chance, or the
      influence of others (eg, physicians). METHODS: A total of 599 cardiac outpatients
      (30% female, 61.4 +/- 9.4 y of age) completed the Multidimensional Health Locus
      of Control questionnaire and a structured health behavior questionnaire assessing
      physical activity, smoking, and alcohol use, at baseline and a 4-y follow-up.
      Relationships between health behaviors and HLOC were assessed cross-sectionally
      and longitudinally using general linear models and logistic regression models
      adjusting for medical and sociodemographic factors. RESULTS: Higher Internal HLOC
      was found to be associated with higher levels of leisure time physical activity
      (LTPA) (beta = .21, P = .0008), while lower Internal HLOC was associated with
      decreasing levels of alcohol consumption over time (beta = .26, P = .03).
      Increasing Chance HLOC was related to lower levels of leisure time physical
      activity (beta = -.15, P = .047) and increased likelihood of being a smoker (beta
      = .10, P = .01), and increasing physician HLOC was associated with decreased
      likelihood of being a smoker (beta = -.17, P = .01). CONCLUSIONS: Associations
      between HLOC and multiple health behaviors were observed in a large sample of
      cardiac outpatients. Results suggest that assessing and targeting HLOC beliefs of
      cardiac patients may be clinically relevant for behavior change in settings, such
      as in rehabilitation programs where behavior change is a goal.

PMID- 30106791
TI  - Advance Care Planning Education Sessions During Pulmonary Rehabilitation in
      Ireland.
AB  - PURPOSE: This study aimed to investigate the practice of advance care planning
      (ACP) education within pulmonary rehabilitation programs (PRPs) in Ireland.
      METHODS: All 27 PRPs in the Republic of Ireland were surveyed between May and
      September 2015, eliciting detailed quantitative and qualitative information about
      ACP education delivery. Data were analyzed using SPSS statistical software and
      content analysis. RESULTS: Twenty-two PRPs (82%) took part in the survey, with
      86% (n = 19) of these being delivered in a hospital setting. Forty-five percent
      (n = 10) included ACP education of at least 20-min duration (n = 5) or as part of
      another session (n = 5). ACP topics discussed differed significantly across PRP
      sites. Sessions were delivered by respiratory nurses, physiotherapists,
      physicians, or palliative care physicians. Of the 12 sites currently not
      providing ACP education, almost half (n = 5) indicated a willingness to include
      this in the near future. Respondents identified enablers and barriers to ACP
      education, as well as staff education and service delivery gaps. CONCLUSIONS:
      Results demonstrate an overwhelmingly positive attitude toward ACP education.
      There is a need for ACP-specific education for all staff members involved in
      PRPs. Practical guidance on how to deliver this patient education component needs
      to be developed.

PMID- 30106792
TI  - Transient Elastography for Monitoring for Hepatotoxicity in Rheumatoid Arthritis
      Patients on Long-term Methotrexate.

PMID- 30106793
TI  - Relapsing Polychondritis Manifesting as Tracheal and Costochondral Inflammation
      on Magnetic Resonance Imaging.

PMID- 30106795
TI  - CORRELATIONS BETWEEN CHOROIDAL STRUCTURES AND VISUAL FUNCTIONS IN EYES WITH
      RETINITIS PIGMENTOSA.
AB  - PURPOSE: To investigate the choroidal structures in the enhanced depth imaging
      optical coherence tomographic images in eyes with retinitis pigmentosa (RP) and
      to determine correlations between the choroidal structures and visual functions.
      METHODS: The enhanced depth imaging optical coherence tomographic images of 100
      eyes with typical RP and 60 age-, sex-, and axial length-matched normal eyes were
      binarized using ImageJ. The cross-sectional luminal and stromal areas of the
      inner and outer subfoveal choroid of 1,500-um width were measured. The inner
      choroid included the choriocapillaris and medium vessel layer, and the outer
      choroid included the larger vessel layer. RESULTS: In the inner choroid, the
      luminal area and the ratio of luminal/total choroidal area (L/C ratio) were
      significantly smaller in RP than in controls (P = 0.010, P < 0.001,
      respectively), whereas the stromal area was not significantly different (P =
      0.114). The inner choroidal L/C ratio was significantly correlated with the best
      corrected visual acuity, mean deviation, foveal sensitivity, width of the
      ellipsoid zone, and central foveal thickness in RP after adjusting for the axial
      length, age, and sex (all P < 0.005). CONCLUSION: The significant correlations
      between the inner choroidal structures and the visual functions and retinal
      structures indicate that the choroidal structures are altered in association with
      the progression of RP.This is an open-access article distributed under the terms
      of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0
      (CCBY-NC-ND), where it is permissible to download and share the work provided it
      is properly cited. The work cannot be changed in any way or used commercially
      without permission from the journal.

PMID- 30106796
TI  - Diagnostic and Therapeutic Challenges.

PMID- 30106794
TI  - Toward a sensible single antigen bead cut-off based on kidney graft survival.
AB  - BACKGROUND: There is no consensus in the literature on the interpretation of
      single antigen bead (SAB) positive for a specific HLA antibody. METHODS: To
      inform the debate, we studied the relationship between various SAB positivity
      algorithms and the impact of resulting donor-specific HLA antibody (DSA)
      positivity on long-term kidney graft survival in 3237 deceased-donor transplants.
      RESULTS: First, we showed that the interassay variability can be greatly reduced
      when working with signal-to-background ratios instead of absolute MFIs. Next, we
      determined pretransplant DSA using various MFI cut-offs, signal-to-background
      ratios (STBR) and combinations thereof. The impact of the various cut-offs was
      studied by comparing the graft survival between the DSA-positive and DSA-negative
      groups. We did not observe a strong impact of various cut-off levels on 10-year
      graft survival. A stronger relationship between the cut-off level and 1-year
      graft survival for DSA-positive transplants was found when using STBR, most
      pronounced for the bead of the same HLA-locus with lowest MFI taken as
      background. CONCLUSIONS: With respect to pretransplant risk stratification, we
      propose a SBTR-6 (using the bead of the same HLA-locus with lowest MFI as
      background) cut-off of 15 combined with an MFI cut-off of 500, resulting in 8%
      and 21% lower 1- and 10-years graft survival, respectively, for 8% DSA positive
      transplants.

PMID- 30106797
TI  - Diagnostic and Therapeutic Challenges.

PMID- 30106798
TI  - Evaluation of the most commonly used (semi-)quantitative parameters of 18F-FDG
      PET/CT to detect malignant transformation of neurofibromas in neurofibromatosis
      type 1.
AB  - In patients with neurofibromatosis type 1, transformation of neurofibromas into a
      malignant peripheral nerve sheath tumor (MPNST) is a severe complication of the
      disease. Fluorine-18-fluorodeoxyglucose PET/computed tomography (PET/CT) is a
      viable option for detecting malignant tumors in neurofibromatosis type 1
      patients. The aim of this review was to assess the diagnostic performance of the
      most frequently used parameters of PET/CT in detecting MPNST. An extensive
      computer search was performed using the Cochrane Library, Pubmed, and
      Medline/Embase databases. Two reviewers independently extracted data of relevant
      studies and assessed the methodological quality (QUADAS-2). The diagnostic
      performance of PET/CT parameters in individual studies was determined by
      calculating a diagnostic odds ratio (DOR) using the absolute numbers of true
      positive, true-negative, false-positive, and false-negative test results. A total
      of eight studies were included, of which three evaluated the standardized uptake
      value as a diagnostic parameter, two assessed the tumor-to-liver (T/L) ratio, and
      three articles described both parameters. The cut-off values for maximum
      standardized uptake value (SUVmax) ranged from 3.2 to 4.5; for the T/L ratio, the
      cut-off values were between 1.0 and 4.3. The sensitivity and specificity ranged
      from 90 to 100% and from 80 to 100%, respectively (SUVmax). T/L ratios were
      associated with 92-100% sensitivity and 72-94% specificity. The corresponding
      DORs ranged from 57 to 145 (SUVmax) and 35 to 655 (T/L ratio). Both the SUV and
      the T/L ratio are associated with high sensitivity combined with acceptable
      specificity in detecting MPNST. There is a tendency toward higher DORs using the
      T/L ratio, but the number of studies is limited.

PMID- 30106799
TI  - CENTRAL RETINAL ARTERY OCCLUSION WITH CILIORETINAL ARTERY SPARING AFTER LASER
      ASSISTED IN SITU KERATOMILEUSIS.
AB  - PURPOSE: To report a central retinal artery occlusion with cilioretinal artery
      sparing in a 48-year-old woman after laser-assisted in situ keratomileusis
      surgery. METHODS: Case history and clinical examination including best-corrected
      visual acuity, serum markers, slit-lamp biomicroscopy, indirect ophthalmoscopy,
      fundus photography, fluorescein angiography, and optical coherence tomography.
      RESULTS: A 48-year-old woman underwent routine laser-assisted in situ
      keratomileusis surgery in both eyes. On postoperative Day 1, vision was 20/20 in
      both eyes with full visual fields by confrontation. Eight hours after being
      examined, she reported photopsias and a new visual field defect in the right eye
      . Visual acuity was 20/40, pinhole 20/20 in the right eye, with restriction of
      visual field by confrontation. Dilated fundus examination revealed retinal
      whitening in all quadrants with sparing of the fovea along the distribution of a
      perfused cilioretinal artery. Optical coherence tomography showed an intact
      foveal depression with inner retinal layer hyperreflectivity outside the region
      of the perfused cilioretinal artery. Fluorescein angiography revealed sectoral
      nonperfusion of the posterior pole with macular sparing along the patent
      cilioretinal artery. Hypercoagulable workup, carotid imaging, and magnetic
      resonance imaging of the brain were unremarkable. CONCLUSION: This is the first
      report of a central retinal artery occlusion with cilioretinal artery sparing
      occurring on postoperative Day 1 after laser-assisted in situ keratomileusis
      surgery.

PMID- 30106801
TI  - Images in Neuro-Ophthalmology.

PMID- 30106800
TI  - Vision: It Is About the Brain.

PMID- 30106802
TI  - Visual Evoked Potentials as a Biomarker in Multiple Sclerosis and Associated
      Optic Neuritis.
AB  - : ABSTRACT:: Multiple sclerosis (MS) is an inflammatory, degenerative disease of
      the central nervous system (CNS) characterized by progressive neurological
      decline over time. The need for better "biomarkers" to more precisely capture and
      track the effects of demyelination, remyelination, and associated neuroaxonal
      injury is a well-recognized challenge in the field of MS. To this end, visual
      evoked potentials (VEPs) have a role in assessing the extent of demyelination
      along the optic nerve, as a functionally eloquent CNS region. Moreover, VEPs
      testing can be used to predict the extent of recovery after optic neuritis (ON)
      and capture disabling effects of clinical and subclinical demyelination events in
      the afferent visual pathway. In this review, the evolving role of VEPs in the
      diagnosis of patients with ON and MS and the utility of VEPs testing in
      determining therapeutic benefits of emerging MS treatments is discussed.

PMID- 30106803
TI  - Acute Management of Optic Neuritis: An Evolving Paradigm.
AB  - The current management of acute optic neuritis (ON) is focused on expediting
      visual recovery through the use of high-dose intravenous corticosteroids. The
      recent identification of specific autoantibodies associated with central nervous
      system inflammatory disorders has provided novel insights into immune targets and
      mechanisms that impact the prognosis, treatment, and recurrence of ON. Therefore,
      neurologists and ophthalmologists need to be aware of clinical, laboratory, and
      imaging findings that may provide important clues to the etiology of ON and the
      potential need for aggressive management. Moving forward, rapid and accurate
      diagnosis of inflammatory ON will likely be critical for implementing clinical
      care that optimizes short-term and long-term therapeutic outcomes.

PMID- 30106804
TI  - A Case of Atypical Leber Hereditary Optic Neuropathy With Slow, Symmetrical
      Progression Over Three Years.

PMID- 30106805
TI  - Digital-Facial Translocation in Amniotic Band Sequence: Evidence of the Intrinsic
      Theory.
AB  - Amniotic band sequence is a complex congenital anomaly in which infants with
      typically no known genetic mutation have bands of maternal amniotic tissue
      wrapped around body parts, most commonly the limbs and digits. The authors report
      a novel variation on this presentation in 3 patients from 2 centers with complex
      craniofacial clefting and amniotic band sequence. They presented with
      hypertelorism, different forms of complex craniofacial clefting, and bands
      connecting ipsilateral hands to facial clefts, with digital-facial translocation
      in 2 cases. These findings support a model in which complex craniofacial clefts
      result in areas of exposed, sticky, and temporally and spatially coincident
      mesenchyme within the embryo that are susceptible to adherence of ipsilateral
      fetal hands. This strongly supports the intrinsic and adhesion theories of the
      etiology of amniotic band syndrome.

PMID- 30106806
TI  - Prevention of Earlobe Keloid Recurrence After Excision: Assessment of the Value
      of Presurgical Injection of Triamcinolone.
AB  - The ear is commonly involved in keloid formation, being often pierced. This study
      estimates the value of pre-excision triamcinolone injection of earlobe keloid, by
      comparing recurrence rates in patients who only received postexcision
      triamcinolone injection to those who had it administered before and after
      excision.The prospective intervention study involved 18 keloid lesions in as many
      consenting patients who presented with pedunculated earlobe keloid from January
      2005 to January 2007.Triamcinolone doses were administered 10 mg/cm of lesion or
      sutured excision site. Each patient was followed-up for 10 years. Aggregate
      length of keloid lesions at presentation was 24.4 cm in Group A and 26.5 cm in
      Group B. Aggregate length of postexcision sutured wound in Group A was 16.1 cm,
      and 14.8 cm in Group B. Group A patients received a total of 1610 mg of
      triamcinolone, while a total of 4660 mg of same drug was administered to Group B
      patients, among whom 3180 mg was delivered presurgically. Total number of clinic
      visits during the course of treatment in Group A was 10, while that of Group B
      was 22. No patient with recurrent keloid was recorded in both groups.The authors
      concluded that there is no advantage to presurgical injection of triamcinolone
      when excision is considered as part of treatment protocol of a keloid lesion.
      This study helps to eliminate an ostensibly needless part of a commonly used
      treatment protocol.

PMID- 30106807
TI  - Effect of Mannitol Infusion on Optic Nerve Injury After Acute Traumatic
      Subarachnoid Hemorrhage and Brain Injury.
AB  - The primary aim of this paper is to investigate the neuroprotective and
      antiinflammatory effects of mannitol on optic nerve injury after acute traumatic
      subarachnoid hemorrhage and brain injury in rat models. Traumatic brain injury
      (TBI) and traumatic subarachnoid hemorrhage (tSAH) were produced by a custom-made
      weight-drop impact acceleration device. Thirty male Wistar rats were divided into
      3 groups. Group I (n = 10) was the sham group, group II (n = 10) received TBI,
      and group III (n = 10) received TBI + mannitol (1 mg/kg intravenously). Optic
      nerve tissue glutathione peroxidase (GPx) and interleukin 1 beta (IL-1beta)
      levels were measured 4 hours after the trauma. The authors used Kruskal-Wallis
      variance analysis and Mann-Whitney U tests for statistical analysis. Optic nerve
      tissue GPx levels were significantly higher in group III than in groups I and II
      (P < 0.05). Optic nerve tissue IL-1beta levels were significantly lower in group
      III than in group II (P < 0.05) and higher than in group I (P < 0.05).Mannitol
      increased the antioxidant GPx levels and decreased the IL-1beta levels, which can
      protect the optic nerve from secondary injury after severe acute trauma. Mannitol
      plays an important role in the treatment of acute severe indirect optic nerve
      injury after TBI and tSAH.

PMID- 30106808
TI  - Review of "Strategies for Reducing Population Surgical Costs in Medicare: Local
      Referrals to Low-cost Hospitals" by Nathan H, Thumma JR, Norton EC, Dimick JB in
      Ann Surg 267:878-885, 2018.

PMID- 30106809
TI  - Lingual Nerve Entrapment in Fused Submandibular and Sublingual Salivary Glands: A
      Unique Finding.
AB  - Lingual nerve (LN) is one among the 3 branches of posterior division of
      mandibular nerve. It might get entrapped in the infratemporal fossa by lateral
      pterygoid muscle, pterygospinous ligament, or lateral pterygoid plate. Its
      entrapment in the submandibular region has not been reported yet. A unique
      entrapment of LN in the fused submandibular and sublingual salivary glands in a
      cadaver was reported. The deep parts of the submandibular and sublingual salivary
      glands were completely fused with each other. The LN passed through the center of
      the fused part. Histologically both submandibular and sublingual salivary glands
      had both mucous and serous acini. Though this entrapment might not cause any
      functional problems, it might get injured during various surgical procedures of
      the submandibular region.

PMID- 30106810
TI  - Syngnathia.
AB  - Syngnathia is a congenital fusion of the upper and lower jaws. Its occurrence
      poses a significant challenge to feeding and its management is challenging to
      both the surgeon and the anaesthetist. Reports in the literature are mainly
      clinical reports or case series. To the knowledge of the authors and from the
      available literature, this is only the fourth report from Nigeria. The
      presentation and successful management of a Nigerian female neonate with
      congenital syngnathia is described and reviewed with literature.

PMID- 30106811
TI  - A Modified Pre-Auricular Approach in the Treatment of Orbital Zygomatic Maxillary
      Complex Fractures.
AB  - OBJECTIVE: This study aimed to evaluate the safety of a modified pre-aricular
      approach in the treatment of orbital zygomatic maxillary complex fractures.
      METHODS: This was a retrospective study of clinical data from 108 adults who were
      diagnosed with orbital zygomatic maxillary complex fractures and undergo open
      reduction and internal fixation through a modified pre-auricular approach.
      Exophthalmometry and limitation of extraocular muscle movement were determined
      using a Hertel exophthalmometer or synoptophore examination respectively. Primary
      complications were recorded, and postoperative facial nerve injury was tested by
      electrophysiologic analysis. RESULTS: All patients received satisfied functional
      and cosmetic results at least 6 moths postoperatively. There were 2 cases (1.85%)
      involving complete or incomplete facial nerve injury confirmed by
      electrophysiologic analysis. The incidence of other postoperative complications
      including a hematoma rate of 1.85% patients and permanent hypesthesia or
      paresthesia in 2.78% of patients, and no cases of clinically significant temporal
      hollowing, alopecia, infection, or unacceptable scars encountered during a mean
      follow-up period of 2 years. CONCLUSION: A modified pre-auricular approach with
      dissection deep to the temporalis fascia offers a safe and reliable surgical
      technique for accessing the malar arch in orbital zygomatic maxillary complex
      fractures.

PMID- 30106812
TI  - Anthropometric Analysis of the Nigerian Face: Any Conformity to the Neoclassical
      Canons?
AB  - This study defines the facial anthropometric and aesthetic measurements in young
      Nigerians. This is a prospective cohort study involving facial anthropometric
      measurement in young adults without craniofacial abnormalities. Ten
      anthropometric measurements (upper facial height (tr-n), mid-facial height (n
      sn), lower facial height (sn-gn), height of auricle (sa-sba) bilaterally,
      intercanthal width (en-en), palpebral fissure width (en-ex) bilaterally, face
      width (zy-zy), nose width (al-al), mouth width (ch-ch) and the interincisal
      distance) were determined. Proportions were compared with neoclassic cannons,
      published North American and Asian norms 151 individuals consisting of 50 males
      and 51 females with age range from 16 to 31 (23.9 + 2.49) were enrolled. Only 1%
      of the study population had equal facial thirds, the midface was the shortest of
      the facial thirds and the male gender generally had larger mean values of the
      facial dimensions than the female gender. About half of the participants had the
      lower third > upper third > middle third, the intercanthal width was equal to the
      nasal width in only about a tenth of the participants and less than the nasal
      width in majority (88.1%) of the participants and the mean interincisal distance
      was 51.1 (SD +/- 6.997). The anthropometric measurements from this Nigerian study
      do not conform to the neoclassical cannons. Racially sensitive facial canons and
      measurements are advocated during reconstructive and aesthetic interventions in
      the craniofacial region.

PMID- 30106813
TI  - Retained Eyeglasses in the Orbital Cavity After Penetrating Facial Trauma.
AB  - This study describes a 68-year-old man who was presented to the emergency
      department with left orbital cavity penetration by his eyeglasses. The eyeglasses
      had entered the orbit and at presentation his eyesight could not be measured. The
      foreign body was extracted carefully and panfacial bone fractures were then
      reduced through lateral rhinotomy combined with a lip-splitting incision. When
      planning removal of an unusual foreign body from the orbital cavity, care should
      be taken not to injure the optic nerve, periorbital musculatures, or the eyeball.

PMID- 30106814
TI  - Effect of Immediate Loop Electrode Excisional Procedure for High-Grade Cervical
      Cytology in an Urban Academic Clinic Setting.
AB  - OBJECTIVE: The aim of the study was to determine whether treating all patients
      older than 25 years with high-grade squamous intraepithelial lesion (HSIL) Paps
      with immediate loop electrode excisional procedure (LEEP) improves rates of
      receiving indicated treatment and evaluating whether this practice results in
      overtreatment (defined by excisional pathology less than cervical intraepithelial
      neoplasia 2). MATERIALS AND METHODS: This was a retrospective cohort study at an
      urban, Medicaid-based clinic, which evaluated women older than 25 years with HSIL
      Pap results seen from June 2011 to December 2016. In June 2013, the clinic
      practice was restructured and management of HSIL Pap results in patients older
      than 25 years was standardized to immediate LEEP procedure, without intermediate
      colposcopic examination. Our primary outcome is the number of women who received
      LEEPs before and after this clinical practice change. The secondary outcome
      evaluated the number of women who received overtreatment. The chi test with a p
      value of 0.05 as significant was used to compare the results between groups.
      RESULTS: Twenty-three (82%) of the 28 women treated before clinical practice
      change received indicated treatment, with 19 receiving LEEPs. Twenty-four (96%)
      of the 25 women treated after the clinical practice change received indicated
      LEEPs (p = .11). Seven (37%) of the 19 women in the initial group had LEEP
      pathology results less than CIN 2, whereas only 4 (17%) of the 24 women in the
      immediate LEEP group had results less than CIN 2 (p = .13). CONCLUSIONS:
      Implementation of a standardized management of HSIL Pap with immediate LEEP did
      not statistically increase the amount of patients who received indicated LEEPs;
      however, implementation of this practice did not result in overtreatment.

PMID- 30106815
TI  - Cervical Adenoid Basal Carcinoma: Clinicopathologic Features of 9 Cases With
      Reference to CK17 and Ki-67 Expression.
AB  - OBJECTIVE: The aims of this study were to clarify the histological features of
      adenoid basal carcinoma (ABC) and determine whether cytokeratin 17 (CK17) and Ki
      67 can facilitate the differential diagnosis of ABC from squamous cell carcinoma
      (SCC). MATERIALS AND METHODS: Nine cases of pure ABC were collected from the
      files of the Division of Pathology at the Zhejiang University Hospital Women's
      School of Medicine. For comparison, 20 cases of moderately to poorly
      differentiated cervical SCC, including 2 of basaloid SCC, were also retrieved
      from the same period. Blocks were recut, reread, and immunostained for CK17 and
      Ki-67. RESULTS: Morphologically, ABCs were mainly composed of small basaloid cell
      nests and variable squamous differentiation foci. For immunohistochemical
      staining, 1 of 9 cases showed diffuse CK17 staining, 5 of 9 showed focal positive
      staining, and 3 of 9 showed negative staining in the basaloid cell area of ABC,
      whereas no CK17 expression was found in ABC squamous foci. Eighteen of the 20
      invasive SCCs showed diffuse CK17 staining, and 2 showed focal staining. The Ki
      67 proliferative index varied in different ABC areas, with a relatively high
      index in squamous differentiation foci and a low index in basaloid cell areas. In
      contrast, Ki-67 staining was unevenly intense in SCC. CONCLUSIONS: Adenoid basal
      carcinoma had characteristic morphological features, and the differential
      diagnosis of ABC from SCC is usually simple, based on morphology. In select
      cases, when histological findings are equivocal, the loss of CK17 expression in
      the squamous differentiation area, and a lower Ki-67 index in basal cell foci
      support ABC diagnosis.

PMID- 30106816
TI  - Sagittal Balance and Health-Related Quality of Life Three Decades After in Situ
      Arthrodesis for High-Grade Isthmic Spondylolisthesis.
AB  - BACKGROUND: This case series of consecutive patients evaluated sagittal balance
      and health-related quality of life (HRQoL) 3 decades after in situ arthrodesis
      for high-grade isthmic spondylolisthesis. METHODS: Global sagittal balance,
      pelvic parameters, and compensatory mechanisms were evaluated on standing lateral
      radiographs of the spine and pelvis for 28 of 39 consecutive patients, 28 to 41
      years after in situ arthrodesis for high-grade L5 to S1 spondylolisthesis. The
      mean age at surgery was 14 years (range, 9 to 24 years), and the mean age at the
      time of follow-up was 48 years (range, 39 to 59 years). A subset of the
      radiographic parameters was compared with the corresponding data from an 8-year
      follow-up examination of the same patients. HRQoL was evaluated with the
      Scoliosis Research Society (SRS)-22r questionnaire. RESULTS: We found that 3 of
      the 28 patients had a global sagittal imbalance (T1 spinopelvic inclination of >0
      degrees ). Signs of compensatory mechanisms, such as reduced thoracic kyphosis
      and pelvic retroversion, were frequent. There was a significant decrease in
      sacral slope compared with 8-year follow-up data (p = 0.01). The median SRS-22r
      subscore was on the same level as Swedish normative data. We found no association
      between radiographic parameters and SRS-22r outcome. CONCLUSIONS: Three decades
      after in situ arthrodesis for high-grade spondylolisthesis, radiographic signs of
      noncompensated sagittal imbalance were observed in only a few individuals. The
      patients had normal SRS-22r scores. There was no association between any
      radiographic parameter and SRS-22r outcome. The findings are relevant in the
      controversial discussion on whether to perform a reduction procedure to treat
      high-grade spondylolisthesis. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30106817
TI  - Type of Anticoagulant Used After Total Knee Arthroplasty Affects the Rate of Knee
      Manipulation for Postoperative Stiffness.
AB  - BACKGROUND: The aim of this study was to perform a population-level analysis on
      the effect of different types of anticoagulation on postoperative stiffness after
      total knee replacement, requiring manipulation under anesthesia. We hypothesized
      that patients receiving warfarin would have a higher rate of manipulation under
      anesthesia compared with patients receiving low-molecular-weight heparin. We also
      hypothesized that aspirin, direct factor Xa inhibitors, and fondaparinux would
      have no effect on the rate of manipulation under anesthesia. METHODS: Using the
      PearlDiver patient database, we analyzed 32,320 patients who underwent a primary
      unilateral total knee replacement from 2007 to 2015. Patients were included if
      they filled a prescription for anticoagulation medication within 2 days of their
      discharge and were excluded if they were taking a prescription anticoagulation
      medication (except for aspirin) in the 3 months before total knee replacement.
      The primary outcome was manipulation under anesthesia performed within 6 months
      after a primary total knee replacement. RESULTS: The most commonly prescribed
      postoperative anticoagulation was warfarin (38.0%), followed by low-molecular
      weight heparin (33.8%). There were 1,178 patients (3.64%) who underwent
      manipulation under anesthesia within 6 months of total knee replacement. In
      multivariable analysis using low-molecular-weight heparin as a comparison group
      and accounting for age, sex, comorbidities, and length of stay, there was a
      significant increase in the risk of manipulation under anesthesia for patients
      who received warfarin (hazard ratio [HR], 1.17 [95% confidence interval (CI),
      1.01 to 1.36]; p = 0.032), direct factor Xa inhibitors (HR, 1.42 [95% CI, 1.20 to
      1.66]; p < 0.001), or fondaparinux (HR, 1.33 [95% CI, 1.01 to 1.72]; p = 0.038).
      Although patients who received aspirin had the same risk estimate as patients who
      received warfarin, there was not a significantly increased risk of manipulation
      under anesthesia in patients who received aspirin compared with low-molecular
      weight heparin (HR, 1.17 [95% CI, 0.72 to 1.80]; p = 0.493). CONCLUSIONS: We
      found an increased rate of manipulation under anesthesia after total knee
      replacement in patients who received oral anticoagulants including warfarin,
      direct factor Xa inhibitors, and fondaparinux, in comparison with patients who
      received aspirin or low-molecular-weight heparin. We recommend that patients
      receiving oral anticoagulants after total knee replacement should be counseled
      about associated stiffness. Furthermore, surgeons should take these data into
      account when selecting thromboprophylaxis for patients after total knee
      replacement. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for
      Authors for a complete description of levels of evidence.

PMID- 30106818
TI  - Interscalene Block with and without Intraoperative Local Infiltration with
      Liposomal Bupivacaine in Shoulder Arthroplasty: A Randomized Controlled Trial.
AB  - BACKGROUND: Interscalene brachial plexus blockade (ISBPB) is an effective
      anesthetic technique for shoulder arthroplasty; however, "rebound pain" can
      increase the patient's postoperative pain experience and narcotic usage. Exparel
      (liposomal bupivacaine) injected into the soft tissues at the surgical site has
      theoretical efficacy for up to 72 hours after administration. The purpose of this
      study was to evaluate postoperative pain scores and narcotic consumption
      following shoulder arthroplasty performed with either ISBPB alone or ISBPB and
      intraoperative Exparel. METHODS: Seventy-eight patients undergoing primary
      shoulder arthroplasty were randomized to receive an ISBPB with Exparel (39
      patients) or without Exparel (39 patients). The primary outcome variable was
      morphine equivalent units (MEUs) consumed over the first 24 hours after surgery.
      Secondary outcomes included intraoperative narcotic administration and visual
      analog scale (VAS) scores for pain (at 0, 8, 16, 24, 48, and 72 hours after
      surgery). RESULTS: There were no significant demographic differences between the
      ISBPB and ISBPB + Exparel groups. Total narcotic consumption over the first 24
      hours after surgery was significantly lower in the ISBPB group compared with the
      ISBPB + Exparel group (mean and standard deviation, 18.9 +/- 25.6 MEU versus 35.3
      +/- 36.7 MEU, p = 0.009). VAS pain scores did not differ significantly between
      groups at any time point during the first 72 hours after surgery. CONCLUSIONS:
      Patients treated with Exparel required significantly more postoperative narcotics
      and demonstrated no significant reduction in pain scores over the first 72 hours
      after primary shoulder arthroplasty. Exparel does not appear to have substantial
      value when added to a pain protocol that includes an ISBPB. LEVEL OF EVIDENCE:
      Therapeutic Level l. See Instructions for Authors for a complete description of
      levels of evidence.

PMID- 30106819
TI  - Free Vascularized Medial Femoral Condyle Bone Graft After Failed Scaphoid
      Nonunion Surgery.
AB  - BACKGROUND: Outcomes following revision surgery for scaphoid nonunions with
      osteonecrosis are guarded. We hypothesized that use of free vascularized medial
      femoral condyle (MFC) bone grafts can lead to healing of the nonunion, increase
      vascularity of the proximal pole, and restore scaphoid architecture, resulting in
      acceptable functional outcomes. METHODS: We performed a retrospective review of
      49 patients who were treated with an MFC bone graft, between May 2005 and
      September 2016, after prior failure of operative treatment for scaphoid nonunion.
      The mean time from the injury to the revision surgery with the MFC bone graft was
      24 months, and the mean time from the prior, failed surgery was 15 months. Thirty
      six of the 49 patients had had a prior bone graft procedure and 6 patients had
      had 2 previous surgical procedures for the nonunion. The initial internal
      fixation of the scaphoid fracture was with a scaphoid screw in 43 patients. All
      patients had documented osteonecrosis of the proximal pole at the time of our
      surgery. Carpal indices, time to union, pain scores, functional outcomes, and
      complications were recorded. RESULTS: Forty-one (84%) of the 49 previously
      operated on scaphoid nonunions healed at a mean of 16 weeks (range, 9 to 31
      weeks) after the MFC bone-grafting as confirmed on computed tomography (CT).
      Radiographs demonstrated significant improvement in carpal alignment following
      the surgery with the MFC bone graft. Comparison between preoperative and
      postoperative values showed a trend toward improved grip strength and no
      important change in total wrist range of motion. Subsequent procedures were
      performed in 29 patients, 21 of whom had planned Kirschner wire removal. All 24
      patients in whom scaphoid union had been achieved and who were available for
      follow-up were able to work or attend school full-time, and 88% were satisfied or
      very satisfied with their wrist function. Age, smoking status, body mass index,
      time to surgery, and preoperative radiographic findings were not found to be
      significant predictors of failure. CONCLUSIONS: MFC grafts increase vascularity
      and restore scaphoid architecture, promoting union in most patients with the
      combination of proximal pole osteonecrosis, carpal collapse, and failed prior
      scaphoid nonunion surgery. LEVEL OF EVIDENCE: Therapeutic Level IV. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30106820
TI  - Medical Costs of Delayed Hip Fracture Surgery.
AB  - BACKGROUND: Waiting for hip fracture surgery is associated with complications.
      The objective of this study was to determine whether waiting for hip fracture
      surgery is associated with health-care costs. METHODS: We conducted a population
      based, propensity-matched cohort study of patients treated between 2009 and 2014
      in Ontario, Canada. The primary exposure was early hip fracture surgery,
      performed within 24 hours after arrival at the emergency department. The primary
      outcome was direct medical costs, estimated for each patient in 2013 Canadian
      dollars, from the payer perspective. The costs in the early and delayed groups
      were then compared using a difference-in-differences approach: the baseline cost
      in the year prior to the hip fracture that had been accrued by patients with
      early surgery was subtracted from the cost in the first year following the
      surgery (first difference), and the difference was then compared with the same
      difference among propensity-score-matched patients who had received delayed
      surgery (second difference). The secondary outcome was the postoperative length
      of stay (in days). RESULTS: The study included 42,230 patients who received hip
      fracture surgery from a total of 522 different surgeons at 72 hospitals. The mean
      cost (and standard deviation) attributed to the hip fracture was $39,497 +/-
      $46,645 per person. The matched patients who underwent surgery after 24 hours had
      direct 1-year medical costs that were an average of $2,638 higher (95% confidence
      interval [CI] = $1,595 to $3,680, p < 0.0001) and a postoperative length of stay
      that was an average of 0.610 day longer (95% CI = 0.1749 to 1.0331 days, p =
      0.0058) compared with those who underwent surgery within 24 hours. CONCLUSIONS:
      Waiting >24 hours for hip fracture surgery was associated with increased medical
      costs and length of stay. Costs incurred by waiting may provide a financial
      incentive to mitigate delays in hip fracture surgery. LEVEL OF EVIDENCE: Economic
      Level III. Please see Instructions for Authors for a complete description of
      levels of evidence.

PMID- 30106821
TI  - Factors Associated with Atraumatic Posterosuperior Rotator Cuff Tears.
AB  - BACKGROUND: Certain metabolic factors have been proposed as risk factors for a
      posterosuperior rotator cuff tear. Although metabolic syndrome is of increasing
      concern in industrialized societies, little information exists regarding its
      association with posterosuperior rotator cuff tears. The purpose of this study
      was to determine the risk factors for an atraumatic posterosuperior rotator cuff
      tear, including metabolic factors and metabolic syndrome. METHODS: This study
      involved 634 subjects (634 shoulders) drawn from a cohort of rural residents.
      Posterosuperior rotator cuff tear diagnoses were based on magnetic resonance
      imaging (MRI) findings. Logistic regression analysis was used to determine the
      odds ratios (ORs) and 95% confidence intervals (CIs) for various demographic,
      physical, and social factors, including age, sex, dominant-side involvement, body
      mass index (BMI), and participation in manual labor; the comorbidities of
      diabetes, hypertension, dyslipidemia, thyroid dysfunction, ipsilateral carpal
      tunnel syndrome, and metabolic syndrome; and the serum metabolic parameters of
      serum lipid profile, glycosylated hemoglobin A1c, and level of thyroid hormone.
      Two multivariable analyses were performed: the first excluded metabolic syndrome
      while including diabetes, hypertension, BMI, and hypo-high-density
      lipoproteinemia (hypo-HDLemia), and the second included metabolic syndrome while
      excluding the formerly included variables. RESULTS: Age, BMI, waist
      circumference, dominant-side involvement, manual labor, diabetes, hypertension,
      metabolic syndrome, ipsilateral carpel tunnel syndrome, HDL (high-density
      lipoprotein), and hypo-HDLemia were significantly associated with posterosuperior
      rotator cuff tears in univariate analyses (p <= 0.035). In the first
      multivariable analysis, age (OR. 1.86 [95% CI, 1.47 to 2.35]), BMI (OR, 1.09 [95%
      CI, 1.02 to 1.18]), dominant-side involvement (OR, 2.04 [95% CI, 1.38 to 3.01]),
      manual labor (OR, 9.48 [95% CI, 5.13 to 17.51]), diabetes (OR, 3.38 [95% CI, 1.98
      to 5.77]), and hypo-HDLemia (OR, 2.07 [95% CI, 1.30 to 3.29]) were significantly
      associated with posterosuperior rotator cuff tears (p <= 0.019). In the second
      multivariable analysis, age (OR, 1.85 [95% CI, 1.48 to 2.31]), dominant-side
      involvement (OR, 1.83 [95% CI, 1.26 to 2.67]), manual labor (OR, 7.71 [95% CI,
      4.33 to 13.73]), and metabolic syndrome (OR, 1.98 [95% CI, 1.35 to 2.91]) were
      significantly associated with posterosuperior rotator cuff tears (p <= 0.002).
      CONCLUSIONS: The metabolic factors of diabetes, BMI, hypo-HDLemia, and metabolic
      syndrome were significant independent factors associated with the development of
      posterosuperior rotator cuff tears. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30106822
TI  - Incorporation and Remodeling of Structural Allografts in Acetabular
      Reconstruction: Multiscale, Micro-Morphological Analysis of 13 Pelvic Explants.
AB  - BACKGROUND: Total hip arthroplasty (THA) is frequently accompanied by acetabular
      bone loss, which constitutes a major challenge in revision procedures. Structural
      allografts can be implanted to restore a stable osseous foundation for the
      acetabular prosthesis. As previous studies were limited to clinical data or
      included very few cases, the extent to which the graft bone is incorporated over
      time has remained unclear. METHODS: Thirteen acetabula were retrieved post
      mortem, and the incorporation properties of the bone allografts were analyzed
      using a hierarchical approach of imaging techniques including contact
      radiography, high-resolution peripheral quantitative computed tomography (HR
      pQCT), histological analysis of undecalcified specimens, and quantitative
      backscattered electron imaging (qBEI). The distance between the current allograft
      bone and host bone borders (i.e., current overlap) as well as the distance
      between the original allograft bone and host bone borders (i.e., total ingrowth)
      were assessed. RESULTS: In 10 of 13 cases, the complete interface (100%) was
      characterized by direct contact and additional overlap of the allograft bone and
      host bone, while the remaining 3 cases demonstrated direct contact along 25% to
      80% of the interface. The allograft bone showed an intact trabecular structure
      and significantly higher mineralization compared with the host bone. The mean
      current overlap (and standard deviation) was 2.3 +/- 1.0 mm, with a maximum of
      5.3 +/- 2.4 mm. Importantly, the total ingrowth reached much further, to a mean
      of 7.2 +/- 2.3 mm (maximum, 10.5 +/- 4.0 mm). Neither the time that the allograft
      was in situ nor the degree of contact between the host and allograft bone
      correlated with the current overlap and the time in situ did not correlate with
      total ingrowth. CONCLUSIONS: This study showed bone remodeling with subsequent
      interconnection of the host and allograft bone along the majority of the
      interface, leading to adequate incorporation of the allograft. The lack of
      complete incorporation of the graft did not lead to graft collapse up to 22 years
      after revision surgery. CLINICAL RELEVANCE: Our study provides the first
      systematic multiscale evaluation of successfully implanted structural allografts
      and forms the scientific basis for their clinical use in revision THA.

PMID- 30106824
TI  - Postoperative Blood Glucose Levels Predict Infection After Total Joint
      Arthroplasty.
AB  - BACKGROUND: Perioperative hyperglycemia has many etiologies, including
      medication, impaired glucose tolerance, uncontrolled diabetes mellitus, or
      stress, the latter of which is common in patients postoperatively. Our study
      investigated the influence of postoperative blood glucose levels on
      periprosthetic joint infection after elective total joint arthroplasty to
      determine a threshold for glycemic control for which surgeons should strive
      during a patient's hospital stay. METHODS: A single-institution retrospective
      review was conducted on 24,857 primary total joint arthroplasties performed from
      2001 to 2015. Of these, 13,196 had a minimum follow-up of 1 year (mean, 5.9
      years). Postoperative day 1 morning blood glucose levels were utilized and were
      correlated with periprosthetic joint infection, as defined by the International
      Consensus Group on Periprosthetic Joint Infection. Multivariable analysis was
      used to determine the influence of several important covariates on infection. An
      alpha level of 0.05 was used to determine significance. RESULTS: The rate of
      periprosthetic joint infection increased linearly from blood glucose levels of
      >=115 mg/dL. Multivariable analysis revealed that blood glucose levels were
      significantly associated with periprosthetic joint infection (p = 0.028). The
      optimal blood glucose threshold to reduce the likelihood of periprosthetic joint
      infection was 137 mg/dL. The periprosthetic joint infection rate in the entire
      cohort was 1.59% (1.46% in patients without diabetes compared with 2.39% in
      patients with diabetes; p = 0.001). There was no significant association between
      blood glucose level and periprosthetic joint infection in patients with diabetes
      (p = 0.276), although there was a linear trend. CONCLUSIONS: The relationship
      between postoperative blood glucose levels and periprosthetic joint infection
      increased linearly, with an optimal cutoff of 137 mg/dL. Immediate and strict
      postoperative glycemic control may be critical in reducing postoperative
      complications, as even mild hyperglycemia was significantly associated with
      periprosthetic joint infection. LEVEL OF EVIDENCE: Prognostic Level III. See
      Instructions for Authors for a complete description of levels of evidence.

PMID- 30106823
TI  - Effects of Upper-Extremity Surgery on Manual Performance of Children and
      Adolescents with Cerebral Palsy: A Multidisciplinary Approach Using Shared
      Decision-Making.
AB  - BACKGROUND: Little is known about the effects of upper-extremity surgery on the
      manual performance of children and adolescents with cerebral palsy (CP). This
      clinical cohort study describes our experience with patient selection based on
      multidisciplinary assessment and shared decision-making and the effects of upper
      extremity surgery on manual performance and patient-relevant outcomes. METHODS:
      All patients (up to 20 years of age) with CP referred to our multidisciplinary
      team for evaluation for upper-extremity surgery between July 2011 and May 2017
      were included. Suitability for upper-extremity surgery was assessed with
      comprehensive, multidisciplinary screening, and the decision to proceed with
      surgery was made together with the patient. Individual patient-relevant goals
      were identified with the Canadian Occupational Performance Measure (COPM);
      perceived independence in performing bimanual activities at home was assessed
      with the ABILHAND-Kids tool, and perceived quality of use of the affected hand
      during daily activities was assessed with a visual analog scale (VAS). The
      quality of use of the affected hand during bimanual performance was measured with
      the Assisting Hand Assessment (AHA), and gross manual dexterity was evaluated
      with the Box and Block Test (BBT). All baseline assessments were repeated at an
      average of 9 months after the surgery. RESULTS: Of 66 patients assessed by the
      multidisciplinary upper-extremity-surgery team, 44 were considered eligible for
      upper-extremity surgery. Of these patients, 39 (mean age and standard deviation
      [SD], 14.9 +/- 2.10 years, 87% with unilateral CP, and 72% at Manual Ability
      Classification System [MACS] level II) underwent upper-extremity surgery and were
      evaluated in the pre-post study. All outcomes improved significantly after upper
      extremity surgery, with average improvements of 3.1 +/- 1.6 points in the COPM
      Performance (COPM-P) score (p < 0.001), 3.3 +/- 2.1 points in the COPM
      Satisfaction (COPM-S) score (p < 0.001), 1.5 +/- 1.2 logits in the ABILHAND score
      (p < 0.001), 2.4 +/- 1.9 cm in the VAS score (p < 0.001), 6.7 +/- 4.2 units in
      the AHA score (p < 0.001), and 2.2 +/- 5.0 blocks/minute on the BBT (p = 0.021).
      The improvement in the COPM-P, COPM-S, ABILHAND, VAS, AHA, and BBT scores was
      clinically meaningful in 80%, 77%, 55%, 62%, 71%, and 31% of the patients,
      respectively. CONCLUSIONS: Careful assessment of eligibility for upper-extremity
      surgery, based on multidisciplinary screening and shared decision-making,
      resulted in a clinically relevant improvement in patient-specific functional
      and/or cosmetic goals and manual performance after upper-extremity surgery in
      most patients with CP. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions
      for Authors for a complete description of levels of evidence.

PMID- 30106826
TI  - Supervised and Independent Post-Discharge Rehabilitation Did Not Differ for
      Improving Pain and Function After Unilateral Total Hip Replacement.

PMID- 30106825
TI  - Periostin Promotes Fibroblast Migration and Inhibits Muscle Repair After Skeletal
      Muscle Injury.
AB  - BACKGROUND: Skeletal muscle injury (SMI) can cause physical disability due to
      insufficient recovery of the muscle. The development of muscle fibrosis after SMI
      has been widely regarded as a principal cause of this failure to recover.
      Periostin (Postn) exacerbates tissue fibrosis in various organs. We investigated
      whether Postn is involved in the pathophysiology after SMI. METHODS: Partial
      laceration injuries of the gastrocnemius were created in wild-type (WT) and Postn
      knockout (Postn) mice. We examined the expression of the Postn gene before and
      after SMI. Regeneration and fibrosis of skeletal muscle were evaluated by
      histological analyses, and recovery of muscle strength was measured by
      physiological testing. Immunohistochemistry was used to examine the number and
      proliferative potential of infiltrating fibroblasts in injured muscle. A trans
      well migration assay was used to assess the migration capability of fibroblasts.
      Control immunoglobulin G (IgG) or Postn-neutralizing antibody (Postn-nAb) was
      injected into injured muscle at 7 and 14 days after injury (dpi). We evaluated
      the effects of Postn-nAb on muscle repair after SMI. RESULTS: The expression of
      Postn was dramatically upregulated after SMI. Compared with WT mice, Postn mice
      had improved muscle recovery and attenuated fibrosis as well as a significantly
      reduced number of infiltrating fibroblasts. The proliferative potential of these
      fibroblasts in WT and Postn mice was comparable at 14 dpi; however, the migration
      capability of fibroblasts was significantly enhanced in the presence of Postn
      (mean, 258%; 95% confidence interval, 183% to 334%). Moreover, the administration
      of Postn-nAb inhibited fibroblast infiltration and promoted muscle repair after
      SMI. CONCLUSIONS: Postn exacerbates fibrotic scar formation through the promotion
      of fibroblast migration into injured muscle after SMI. Treatment with Postn-nAb
      is effective for attenuating fibrosis and improving muscle recovery after SMI.
      CLINICAL RELEVANCE: Our findings may provide a potential therapeutic strategy to
      enhance muscle repair and functional recovery after SMI.

PMID- 30106827
TI  - A Single Dose of Antibiotics Before Removal of Orthopaedic Implants Used to Treat
      Below-the-Knee Fractures Did Not Reduce Surgical Site Infections at 30 Days.

PMID- 30106828
TI  - In Displaced Distal Tibial Fractures, Intramedullary Nail and Locking Plate
      Fixation Did Not Differ in Terms of 6-Month Disability.

PMID- 30106829
TI  - What's New in Limb Lengthening and Deformity Correction.

PMID- 30106831
TI  - It Is All About Value Now: The Data You Need to Collect and How to Do It: AOA
      Critical Issues.
AB  - Health care has entered an era where value and quality have become more important
      than just quantity. Patient-reported outcomes are a critical aspect of the value
      equation. Orthopaedic surgeons will need to demonstrate that their treatment
      regimens actually are enhancing their patients' quality of life. In order to do
      this, the collection of prospective patient-reported outcome data will be
      critical. For most patients, this will require the use of a general health survey
      and a disease-specific questionnaire. Currently, most orthopaedic surgeons are
      not collecting this type of data. The questions are: What types of patient
      generated questionnaires can provide the information needed, and how can these
      data be collected in a cost-effective manner? We will discuss what value means to
      payers and what the outcome measures are that are selected by various orthopaedic
      subspecialty societies to evaluate patients who undergo total hip and knee
      arthroplasty as well as patients with shoulder and knee problems, and we will
      review potential strategies to collect prospective patient-outcome data in a cost
      effective manner in the office.

PMID- 30106832
TI  - MFC Bone Graft for Scaphoid Nonunion, Osteonecrosis, and Failed Prior Surgery:
      Three Strikes But Not Necessarily Out: Commentary on an article by Nicholas
      Pulos, MD, et al.: "Free Vascularized Medial Femoral Condyle Bone Graft After
      Failed Scaphoid Nonunion Surgery".

PMID- 30106830
TI  - Enthesis Repair: Challenges and Opportunities for Effective Tendon-to-Bone
      Healing.
AB  - On May 22, 2017, the National Institutes of Health (NIH)/National Institute of
      Arthritis and Musculoskeletal and Skin Diseases (NIAMS) hosted a roundtable on
      "Innovative Treatments for Enthesis Repair." A summary of the roundtable
      discussion, as well as a list of the extramural participants, can be found at
      https://www.niams.nih.gov/about/meetings-events/roundtables/roundtable-innovative
      treatments-enthesis-repair. This paper reviews the challenges and opportunities
      for developing effective treatment strategies for enthesis repair that were
      identified at the roundtable discussion.

PMID- 30106833
TI  - Can Higher Postoperative Blood Glucose Levels Lead to Periprosthetic Joint
      Infection?: Commentary on an article by Michael M. Kheir, MD, et al.:
      "Postoperative Blood Glucose Levels Predict Infection After Total Joint
      Arthroplasty".

PMID- 30106834
TI  - The Diagnostic Yield of Malignancy Comparing Cytology, FISH, and Molecular
      Analysis of Cell Free Cytology Brush Supernatant in Patients With Biliary
      Strictures Undergoing Endoscopic Retrograde Cholangiography (ERC): A Prospective
      Study.
AB  - BACKGROUND: Routine cytology of biliary stricture brushings obtained during
      endoscopic retrograde cholangiopancreatography (ERCP) has suboptimal sensitivity
      for malignancy. We compared the individual and combined ability of cytology,
      fluorescence in situ hybridization (FISH) analysis and PCR-based mutation
      profiling (MP) to detect malignancy in standard biliary brushings. METHODS: We
      performed a prospective study of patients undergoing ERCP using histology or 1
      year follow-up to determine patient outcomes. MP was performed on free-DNA from
      biliary brushing specimens using normally discarded supernatant fluid. MP
      examined KRAS point mutations and tumor suppressor gene associated loss of
      heterozygosity mutations at 10 genomic loci. FISH examined chromosome specific
      gains or losses. RESULTS: A total of 101 patients were included in final analysis
      and 69% had malignancy. Cytology had 26% sensitivity and 100% specificity for
      malignancy. Using either FISH or MP in combination with cytology increased
      sensitivity to 44% and 56%, respectively. The combination of all 3 tests
      (cytology, FISH, and MP) had the highest sensitivity for malignancy (66%). There
      was no difference in the specificity of cytology, FISH or MP testing when
      examined alone or in combination. MP improved diagnostic yield of each procedure
      from 22% to 100%; FISH improved yield to 90%. MP detected 21 malignancies beyond
      that identified by cytology; FISH detected an additional 13. The combination of
      FISH and MP testing detected an additional 28 malignancies. CONCLUSIONS: Both MP
      and FISH are complimentary molecular tests that can significantly increase
      detection of biliary malignancies when used in combination with routine cytology
      of standard biliary brush specimens.This is an open-access article distributed
      under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
      License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
      provided it is properly cited. The work cannot be changed in any way or used
      commercially without permission from the journal.
      http://creativecommons.org/licenses/by-nc-nd/4.0/.

PMID- 30106835
TI  - Fibroscan Reliably Rules Out Advanced Liver Fibrosis and Significant Portal
      Hypertension in Alcoholic Patients.
AB  - BACKGROUND/GOALS: To date, there is no consensus on optimal cut-off values and
      timing of transient elastography (TE, Fibroscan) for fibrosis staging and
      prediction of portal hypertension in alcoholic liver disease. We evaluated the
      accuracy of Fibroscan for the diagnosis of fibrosis and clinically significant
      portal hypertension in alcoholic patients. STUDY: Heavy drinkers admitted to our
      standardized alcohol withdrawal program were evaluated by Fibroscan, by
      transjugular hepatic venous pressure gradient (HVPG) measurement and liver biopsy
      if significant fibrosis was suspected and by upper gastrointestinal endoscopy.
      All investigations were performed within 3 days of admission. Patients who had
      remained abstinent for 2 weeks underwent a second Fibroscan. RESULTS: A total of
      118 patients were included. Fibroscan correlated well with histology and HVPG.
      Negative predictive value of 92% and 93% for ruling out severe fibrosis (>=F3)
      and cirrhosis, and optimal cut-offs at >=11.7, >=15.2, and >=21.2 kPa for F2, F3,
      and F4, respectively, were found. In abstinent patients, a mean decrease of 2.7
      kPa improved concordance between Fibroscan and histology. A TE value of 30.6 kPa
      predicted a HVPG>10 mm Hg with 94% specificity and showed a good negative
      predictive value of 84% for ruling out the presence of varices at endoscopy.
      Steatosis, alcoholic hepatitis, sinusoidal fibrosis, cholestasis, and high
      transaminases did not influence TE values. CONCLUSIONS: Fibroscan is an accurate
      non-invasive method for the diagnosis of fibrosis in alcoholic patients. TE
      values below 11 and 30 kPa likely rule out significant fibrosis and varices,
      respectively.

PMID- 30106836
TI  - Impact of Colonoscopy Bowel Preparation Quality on Follow-up Interval
      Recommendations for Average-risk Patients With Normal Screening Colonoscopies:
      Data From the New Hampshire Colonoscopy Registry.
AB  - BACKGROUND AND AIMS: National guidelines for colonoscopy screening and
      surveillance assume adequate bowel preparation. We used New Hampshire Colonoscopy
      Registry (NHCR) data to investigate the influence of bowel preparation quality on
      endoscopist recommendations for follow-up intervals in average-risk patients
      following normal screening colonoscopies. METHODS: The analysis included 9170
      normal screening colonoscopies performed on average risk individuals aged 50 and
      above between February 2005 and September 2013. The NHCR Procedure Form instructs
      endoscopists to score based on the worst prepped segment after clearing all colon
      segments, using the following categories: excellent (essentially 100%
      visualization), good (very unlikely to impair visualization), fair (possibly
      impairing visualization), and poor (definitely impairing visualization). We
      categorized examinations into 3 preparation groups: optimal (excellent/good)
      (n=8453), fair (n=598), and poor (n=119). Recommendations other than 10 years for
      examinations with optimal preparation, and >1 year for examinations with poor
      preparation, were considered nonadherent. RESULTS: Of all examinations, 6.2%
      overall received nonadherent recommendations, including 5% of examinations with
      optimal preparation and 89.9% of examinations with poor preparation. Of normal
      examinations with fair preparation, 20.7% of recommendations were for an interval
      <10 years. Among those examinations with fair preparation, shorter-interval
      recommendations were associated with female sex, former/nonsmokers, and
      endoscopists with adenoma detection rate >=20%. CONCLUSIONS: In 8453
      colonoscopies with optimal preparations, most recommendations (95%) were
      guideline-adherent. No guideline recommendation currently exists for fair
      preparation, but in this investigation into community practice, the majority of
      the fair preparation group received 10-year follow-up recommendations. A
      strikingly high proportion of examinations with poor preparation received a
      follow-up recommendation greater than the 1-year guideline recommendation.
      Provider education is needed to ensure that patients with poor bowel preparation
      are followed appropriately to reduce the risk of missing important lesions.

PMID- 30106837
TI  - Early Enteral Nutrition Prevent Acute Pancreatitis From Deteriorating in Obese
      Patients.
AB  - GOALS: The aim of this study was to determine a potential strategy to prevent
      acute pancreatitis (AP) from deteriorating in obese patients. BACKGROUND:
      Nutritional support plays a critical role in the treatment of AP. Early enteral
      nutrition (EEN) is considered to be able to protect mucosa of AP patients and
      alleviate inflammatory reactions. Obesity worsen AP prognosis. However, little is
      known about the effects of EEN in obese patients. STUDY: Prospective randomized
      control trial. Subjects with moderately severe AP or severe AP were divided into
      the visceral fat obesity (VFO) group and the non-VFO group by obesity index VFO.
      The patients received "delayed" enteral nutrition (started enteral nutrition
      feeding after the first 48 hours after admission to the hospital: group A:
      patients of non-VFO, n=108; group B: VFO patients, n=88) or EEN (in the VFO
      subgroup, group C: n=91).Occurrence of complication, clinical outcomes, plasma
      levels of cytokines, and intestine gut barrier index were measured at different
      timepoints after admission. RESULTS: VFO was a risk factor for aggravating of AP.
      EEN prevented the VFO patients from developing pancreatic necrotic infection, the
      mechanism of which might be related with inhibiting excessive inflammatory
      reactions, adjusting the imbalance of inflammatory response, and alleviating
      ischemia of intestine mucosa. CONCLUSIONS: The potential strategy, EEN, was able
      to prevent AP from deteriorating in obese patients.

PMID- 30106838
TI  - Updates in Therapeutic Endoscopic Ultrasonography.
AB  - The last decade has seen a dramatic rise in the possibilities of therapeutic
      endoscopic ultrasound (EUS). From EUS fine needle aspiration of cancerous lesion
      to pseudocyst drainage, it has now not only replaced some of the percutaneous
      techniques but has permitted to bypass all together laparoscopic approach for
      patient with altered anatomy or malignant gastric outlet obstruction. This review
      will emphasize the novel therapeutic EUS procedures added to our arsenal.

PMID- 30106839
TI  - Resource Utilization and Outcomes of Medicare Recipients With Chronic Hepatitis B
      in the United States.
AB  - GOALS: To assess the outcomes and resource utilization of chronic hepatitis B (CH
      B) among Medicare beneficiaries. BACKGROUND: CH-B is highly prevalent among
      immigrants from endemic areas. Although incidence of CH-B is stable in the United
      States, CH-B patients have become Medicare eligible. STUDY: We used the inpatient
      and outpatient Medicare database (2005 to 2014). Adult patients with CH-B
      diagnosis were included. One-year mortality and resource utilization were
      assessed. Independent associations with resource utilization and mortality were
      determined using multivariate analysis. RESULTS: Study cohort included 18,603
      Medicare recipients with CH-B. Between 2005 and 2014, number of Medicare
      beneficiaries with CH-B increased by 4.4% annually. The proportion of
      beneficiaries with CH-B who were whites decreased while those who were Asians
      increased (P<0.05). Furthermore, 7.4% of CH-B Medicare cohort experienced
      decompensated cirrhosis, 2.9% hepatocellular carcinoma (HCC) and 11.9% 1-year
      mortality. Although the number of inpatients with CH-B remained stable, the
      number of outpatient encounters increased. Annual total inpatient charges
      increased from $66,610 to $94,221 while these charges for outpatient increased
      from $9257 to $47,863. In multivariate analysis, age [odds ratio (OR), 1.05; 95%
      confidence interval (CI), 1.04-1.05], male gender [OR, 1.24 (95% CI, 1.12-1.38)],
      decompensated cirrhosis [OR, 3.02 (95% CI, 2.63-3.48)], HCC [OR, 2.64 (95% CI,
      2.10-3.32)], and higher Charlson comorbidity index [OR, 1.24 (95% CI, 1.21-1.27)]
      were independently associated with increased 1-year mortality. HCC and higher
      Charlson comorbidity index were also associated with higher inpatient and
      outpatient charges, and inpatient length of stay (all P<0.001). CONCLUSIONS: CH-B
      infection has been rising in Medicare population and is responsible for
      significant mortality and resource utilization.

PMID- 30106840
TI  - Metronidazole-Resistant Trichomoniasis: Beneficial Pharmacodynamic Relationship
      with High-dose Oral Tinidazole and Vaginal Paromomycin Combination Therapy.

PMID- 30106841
TI  - The Public Health Uniform National Data System (PHUND$): A Platform for
      Monitoring Fiscal Health and Sustainability of the Public Health System.
AB  - CONTEXT: Leaders of government agencies are responsible for stewardship over
      taxpayer investments. Stewardship strengthens agency performance that is critical
      to improving population health. Most industries, including health care, and
      public enterprises, such as education, have policies for uniform data reporting
      and financial systems for the application of theoretical analytical techniques to
      organizations and entire systems. However, this is not a mainstreamed practice in
      local and state government public health. PROGRAM: The Public Health Uniform
      National Data System (PHUND$) is a financial information system for local health
      departments that advances the application of uniform practices to close financial
      analytical gaps. A 10-year retrospective overview on the development,
      implementation, and utility of PHUND$ is provided and supported by documented
      program and agency improvements to validate the analytical features and
      demonstrate a best practice. RESULTS: Benefits found from utilizing PHUND$
      included reducing financial risks, supporting requests for increased revenues,
      providing comparative analysis, isolating drivers of costs and deficits,
      increasing workforce financial management skills, enhancing decision-making
      processes, and fostering agency sustainability to support continuous improvements
      in quality and population health. The PHUND$ financial data definitions in the
      data dictionary provided the structure needed for standardized data collection
      and confirmed the feasibility of a standardized public health chart of accounts.
      CONCLUSION: PHUND$ analysis provided evidence on the relationship between
      financial and operational performance, as well as informing strategies for
      managing risks and improving quality. Such analysis is critical to identifying
      financial and operational problems and essential to mitigating financial crisis,
      avoiding disruption of services, and fostering agency sustainability. PHUND$
      additionally serves as an instrument that can guide development of standards that
      measure for agency sound financial management systems.

PMID- 30106842
TI  - Stage-specific incidence trends of melanoma in an English region, 1996-2015:
      longitudinal analyses of population-based data.
AB  - The aim of this study was to examine temporal trends in overall and stage
      specific incidence of melanoma. Using population-based data on patients diagnosed
      with melanoma in East Anglia, England, 1996-2015, we estimated age-standardized
      time trends in annual incidence rates for each stage at diagnosis. Negative
      binomial regression was used to model trends over time adjusted for sex, age
      group and deprivation, and to subsequently examine variation in stage-specific
      trends by sex and age group. The age-standardized incidence increased from 14 to
      29 cases/100 000 persons (i.e. 4% annually). Increasing incidence was apparent
      across all stages but was steepest for stage I [adjusted annual increase: 5%, 95%
      confidence interval (CI): 5-6%, and more gradual for stage II-IV disease (stage
      II: 3%, 95% CI: 2-4%; stage III/IV: 2%, 95% CI: 1-3%)]. Stage II-IV increase was
      apparent in men across age groups and in women aged 50 years or older. Increases
      in incidence were steeper in those aged 70 years or older, and in men. The
      findings suggest that both a genuine increase in the incidence of consequential
      illness and a degree of overdiagnosis may be responsible for the observed
      increasing incidence trends in melanoma in our population during the study
      period. They also suggest the potentially lower effectiveness of public health
      awareness campaigns in men and older people.This is an open access article
      distributed under the Creative Commons Attribution License 4.0 (CCBY), which
      permits unrestricted use, distribution, and reproduction in any medium, provided
      the original work is properly cited. http://creativecommons.org/licenses/by/4.0/.

PMID- 30106843
TI  - Spontaneous Vestibular Schwannoma Regression: A Case-Control Study.
AB  - OBJECTIVE: To explore the nature of spontaneously regressing vestibular
      schwannomas (VS) and identify possible predictive factors for such behavior.
      STUDY DESIGN: Retrospective case control study. SETTING: Tertiary referral
      center, university teaching hospital. PATIENTS: Patients with sporadic VS
      demonstrating spontaneous regression compared with a control group of patients
      with growing VS. INTERVENTIONS: Review of serial magnetic resonance imaging of
      the internal auditory meatus (MRI IAM) and case notes and direct comparison of
      possible related factors between the two groups using univariate analysis. MAIN
      OUTCOME MEASURES: Presenting symptoms, VS size and consistency, patients' age and
      sex, tumor laterality and location, and the neutrophil-to-lymphocyte ratio
      between the two groups. RESULTS: Of the 540 patients on the database 28 (5.2%)
      showed spontaneous regression with a mean follow-up of 122 months. Mean absolute
      and relative regression was 3.9 mm and 25.7%, respectively. 60% of tumors showed
      gradual regression while 25% showed growth followed by regression. Regressing VS
      had a significantly larger size than the control group; while the regressing
      tumors were located further from the fundus than the control group. The remaining
      examined factors did not reach a statistical level of significance. CONCLUSION:
      This is, to our knowledge, the first study comparing a cohort of regressing
      tumors with a control group of growing VS. The finding that the location of
      tumors around the porous, is more common in regressing VS has implications for
      patients' counselling.

PMID- 30106844
TI  - Osteoradionecrosis of the Temporal Bone: An Evidence-Based Approach.
AB  - OBJECTIVES: To perform a systematic review evaluating etiologies, associated
      complications, and management of osteoradionecrosis of the temporal bone (ORNTB).
      METHODS: The authors searched the PubMed, Embase, and Cochrane Library databases
      for relevant literature. Patient demographics, etiologies, treatments, and other
      clinical characteristics were obtained. Treatment success was defined as
      resolution of symptoms at last follow-up. Results were reported using the
      preferred reporting systems for systematic reviews and meta-analysis (PRISMA)
      guidelines. RESULTS: Thirty-eight studies encompassing 364 patients with ORNTB
      were identified. The most common etiologies necessitating radiotherapy included:
      nasopharyngeal carcinoma (n = 133 [36.8%]), parotid tumors (n = 73 [20.2%]), and
      external auditory canal pathology (n = 59 [16.3%]). The mean dose of radiation
      was 58.0 Gy. The mean lag time between radiotherapy and osteoradionecrosis (ORN)
      symptoms was 7.9 years. The most common presenting symptoms were purulent
      otorrhea (33.3%), hearing loss (29.1%), and otalgia (17%). ORNTB complications
      included tympanic membrane perforation (n = 102 [63.8%]) and chronic otitis media
      (n = 16 [10%]). Treatments included lateral temporal bone resection (n = 99
      [28.3%]), conservative treatment (n = 92 [26.3%]), and mastoidectomy (n = 82
      [23.5%]) with 90.9, 89.13, and 59.76% considered successful, respectively.
      CONCLUSIONS: ORNTB is a rare complication of radiotherapy that may present years
      after initial radiation exposure. Management should be aimed at relief of
      presenting symptoms and treatment of ORNTB associated complications. Both
      conservative and surgical measures may adequately control the disease process and
      symptomatology; however, randomized controlled studies comparing treatments would
      serve to further corroborate these findings.

PMID- 30106846
TI  - Next Generation Sequencing of Sporadic Vestibular Schwannoma: Necessity of
      Biallelic NF2 Inactivation and Implications of Accessory Non-NF2 Variants.
AB  - OBJECTIVES: 1) Describe the genetic alterations discovered in a series of
      sporadic vestibular schwannomas (VS). 2) Identify if more clinically aggressive
      variants possess different genetic alterations compared to more indolent-behaving
      VS. METHODS: Fresh frozen tumor and matched peripheral blood leukocytes from 23
      individuals with sporadic VS were analyzed using whole-exome sequencing, tumor
      whole transcriptome expression profiling (mRNA-Seq), and tumor mate-pair
      analysis. Source cases included tumors with fast preoperative growth, giant
      tumors in young patients, tumors with macrocystic change, recurrent tumors
      following radiation or microsurgery, and indolent small tumors with minimal or no
      growth before surgery. Somatic and germ-line alterations of the NF2 gene and
      beyond the NF2 locus were identified and analyzed using complementing analyses.
      RESULTS: Biallelic somatic events involving the NF2 gene were discovered in every
      analyzed tumor specimen with no concurrent NF2 variants identified in matching
      peripheral blood specimens. Thirteen tumors showed loss of one chromosome 22
      (ch22), 4 tumors showed copy-neutral 22q loss of heterozygosity, and 31 unique
      small variants in the NF2 gene were discovered. Of the latter, 10 were essential
      splice site, 11 frame shift, 7 stop gain, 2 missense, and 1 in-frame mutation. No
      other common or recurring NF2 mutations were identified. However, several other
      notable large chromosomal aberrations were discovered including 2 tumors with
      loss of a chromosome 21, 3 with loss of an X or Y chromosome, 1 with copy-neutral
      loss of heterozygosity in chromosome 15, and 1 with loss of 18p and 16q. All of
      these other major chromosomal abnormalities only occurred in tumors demonstrating
      a more aggressive phenotype. CONCLUSIONS: To date, few studies have used whole
      exome sequencing, mate-pair analysis, and RNA-seq to profile genome-wide
      alterations in sporadic VS. Using high-throughput deep sequencing, "two-hit"
      alterations in the NF2 gene were identified in every tumor and were not present
      in peripheral blood supporting that all events were somatic. Type of NF2 gene
      alteration and accessory mutations outside the NF2 locus may predict phenotypic
      expression and clinical course.

PMID- 30106845
TI  - Persistent Oxidative Stress in Vestibular Schwannomas After Stereotactic
      Radiation Therapy.
AB  - OBJECTIVE: Stereotactic radiation therapy is increasingly used to treat
      vestibular schwannomas (VSs) primarily and to treat tumor remnants following
      microsurgery. Little data are available regarding the effects of radiation on VS
      cells. Tyrosine nitrosylation is a marker of oxidative stress following radiation
      in malignant tumors. It is not known how long irradiated tissue remains under
      oxidative stress, and if such modifications occur in benign neoplasms such as VSs
      treated with significantly lower doses of radiation. We immunostained sections
      from previously radiated VSs with an antibody that recognizes nitrosylated
      tyrosine residues to assess for ongoing oxidative stress. STUDY DESIGN:
      Immunohistochemical analysis. METHODS: Four VSs, which recurred after excision,
      were treated with stereotactic radiation therapy. Ultimately each tumor required
      salvage reresection for regrowth. Histologic sections of each tumor before and
      after radiation were immunolabeled with a monoclonal antibody specific to
      nitrotyrosine and compared. Two VSs that underwent reresection of a growing tumor
      remnant without previous radiation therapy served as additional controls.
      RESULTS: Irradiated tumors enlarged in volume by 3.16 to 8.62 mL following
      radiation. Preradiation sections demonstrated little to no nitrotyrosine
      immunostaining. Three of four of irradiated VSs demonstrated increased
      nitrotyrosine immunostaining in the postradiation sections compared with
      preradiation tumor sections. Nonirradiated VSs did not label with the
      antinitrotyrosine antibody. CONCLUSIONS: VSs exhibit oxidative stress up to 7
      years after radiotherapy, yet these VSs continued to enlarge. Thus, VSs that grow
      following radiation appear to possess mechanisms for cell survival and
      proliferation despite radiation-induced oxidative stress.

PMID- 30106847
TI  - The Performance of Patient-reported Outcome Measures as Diagnostic Tools for
      Eustachian Tube Dysfunction.
AB  - OBJECTIVE: To develop and validate a novel patient-reported outcome measure
      (PROM) to distinguish patulous from obstructive Eustachian Tube Dysfunction
      (ETD). To determine accuracy of PROMs and ET function tests as diagnostic tools
      for ETD. STUDY DESIGN: 1) PROM development and validation. 2) Test case-control
      diagnostic accuracy study. INTERVENTIONS: Cambridge ETD Assessment (CETDA) and
      ETDQ-7 PROMs, sonotubometry and tubomanometry ET function tests. SETTING:
      Tertiary referral center. PATIENTS: Cases with patulous (n = 7) or obstructive (n
      = 60) ETD, controls with either no ear symptoms (n = 33), or symptoms arising
      from hearing loss or Meniere's disease (n = 24). MAIN OUTCOME MEASURES: PROMs
      were assessed in terms of internal consistency, ceiling and floor effects, test
      retest reliability and content, structural and criterion validity. PROMs and
      function test sensitivity and specificity was determined as diagnostic tests for
      ETD. RESULTS: The 10-item CETDA was developed. CETDA validity and performance
      were good, though five items suffered floor effects. There was no difference in
      scores for either PROM in the patulous ETD, obstructive ETD, and symptomatic
      control groups. Both PROMS had excellent diagnostic accuracy using only healthy
      controls as comparator for ETD, but specificity was very poor when controls with
      other otological disorders were included. Both objective tests had sensitivity
      and specificity of 63% and 79% for obstructive ETD. CONCLUSIONS: The CETDA and
      ETDQ-7 are not disease-specific and cannot distinguish obstructive from patulous
      ETD subtypes. A relatively weak correlation between sonotubometry and
      tubomanometry results, PROM scores, and the clinical diagnosis suggests that a
      varied core set of outcome measures is required to monitor response to treatments
      for ETD.

PMID- 30106848
TI  - Cochlear Implantation in Organ Transplant Recipients.
AB  - OBJECTIVE: Immunosuppressed individuals who have undergone organ transplants,
      especially children, pose particular challenges in terms of treatment. The aim of
      this study was to analyze the postoperative complication rate of organ transplant
      recipients who have also received a cochlear implant (CI). STUDY DESIGN:
      Retrospective case series. SETTING: Tertiary referral center. INTERVENTION: The
      case series includes 13 kidney, liver, lung, and heart transplant patients. Age
      at treatment ranged from 2 to 71 years, with a total of 17 CIs. MAIN OUTCOME
      MEASURES: Postoperative complications were classified into major and minor, early
      (within 3 mo postoperatively) and late (>3 mo postoperatively). The results were
      compared with those for 13 1:1 matched pairs obtained and from our database and a
      healthy patient collective from our department. RESULTS: The global postoperative
      complication rate was 29.4%. The proportion of patients suffering major
      complications was 17.6%, with 17.6% having minor complications. Complications
      that occurred early accounted for 13.3%, and late for 26.7%. No adults, and 33.0%
      of children, showed any complications after cochlear implantation. The global
      complication rate (29.4%) was significantly increased compared with the matched
      pairs (0%, p = 0.013) and department data (13.8%, p = 0.006; Cramers v = 0.102).
      CONCLUSION: This study demonstrates that organ transplant recipients, and
      especially children, are at increased risk of postoperative complications after
      cochlear implantation in comparison with healthy CI recipients.

PMID- 30106849
TI  - Outcomes Following Modified Tympanomastoidectomy With Soft-wall Reconstruction.
AB  - OBJECTIVE: To report outcomes following modified tympanomastoidectomy with soft
      wall reconstruction (MTMSWR). STUDY DESIGN: Retrospective cohort. SETTING:
      Tertiary referral center. PATIENTS: Forty-seven patients (48 ears) with
      aggressive cholesteatoma undergoing MTMSWR. INTERVENTIONS: Canal wall down (CWD)
      tympanomastoidectomy with temporalis fascia reconstruction of the posterior
      external auditory canal (EAC). MAIN OUTCOME MEASURES: Cholesteatoma recidivism;
      hearing outcomes; degree of soft-wall retraction; time to epithelialization;
      otorrhea. RESULTS: All ears had some form of ossicular compromise. There were 41
      ears with completed surveillance of which 39% demonstrated recidivism for
      cholesteatoma. Of these, 68.8% had a small cholesteatoma foci averaging 3.7 mm.
      Air pure-tone average remained stable or improved for 60.0% and declined <= 20 dB
      for 85.7%. Excluding ears unable to undergo ossicular chain reconstruction, final
      air-bone gap was <= 30 dB for 66.7%. Retraction of the reconstructed wall was
      absent-to-mild in 34.7% and moderate-to-full in 52.1%. Thirteen percent had soft
      wall breakdown. Average time to full epithelialization of the wall was 58.5 days.
      CONCLUSIONS: MTMSWR is an option for restoring the posterior EAC wall following
      CWD surgery. Recidivism is comparable to canal wall up surgery, and hearing
      outcomes are generally better than CWD. Other advantages include rapid
      epithelialization, low rates of otorrhea, and restoration of a self-cleaning EAC
      regardless of retraction into the mastoid cavity.

PMID- 30106850
TI  - Otopathology in the United States: History, Current Situation, and Future
      Perspectives.
AB  - : Human temporal bone studies have documented the pathophysiologic basis of many
      pathologic conditions and diseases affecting the ear, contributing to the
      development of specific clinical knowledge and pathology-oriented treatments.
      Researchers dedicated to the study of anatomy and histology of the temporal bone
      emanated from Europe to the United States during the first part of the 20th
      Century. The first otopathology laboratory was founded in the United States in
      1924, at Johns Hopkins University; over time, the otopathology laboratories
      considered by some authors as "gold mines" for studying ear diseases-became
      numerous and very prolific. However, today, only three of the temporal bone
      laboratories are still running and producing scientific knowledge to the
      Otology/Neurotology field: the ones at Harvard Medical School, University of
      Minnesota, and University of California. Molecular biologic assay techniques and
      new microscopy and computer equipment broadened the possibilities for temporal
      bone studies; however, the current funding for those laboratories are
      insufficient to cover the costs for processing and studying human temporal bones.
      The main objective of this study is to briefly describe the history, current
      situation, and future perspectives of the otopathology laboratories in the United
      States.

PMID- 30106851
TI  - Patient Positioning During In-Office Otologic Procedures Impacts Physician
      Ergonomics.
AB  - OBJECTIVE: The purpose of this study was to evaluate the impact of patient
      positioning on physician ergonomics during in-office otologic procedures. A
      previous simulation study suggested that placing patients supine during in-office
      otology procedures is ergonomically favorable. This study aims to substantiate
      these findings during the routine care of patients in an otolaryngology practice
      setting. STUDY DESIGN: Observational study. SETTING: Outpatient otology clinic
      within tertiary care facility. STUDY SUBJECTS: Two neurotology attending
      physicians. INTERVENTIONS: Physicians performed cerumen removal procedures in the
      office with patients either in the seated position (n = 24) or supine position (n
      = 24). MAIN OUTCOME MEASURES: The rapid upper limb assessment (RULA), a validated
      instrument that measures body positioning with a focus on the upper arm, was used
      to measure ergonomic positioning. RULA scores correlate occupational body
      positioning with a numeric representation of musculoskeletal injury risk ranging
      from 1 (minimal risk) to 7 (very high risk). RESULTS: Overall median RULA scores
      were 4.5 (medium risk) with patients in the seated position, and 2 (low risk)
      with patients in the supine position (p < 0.0001). Similarly, RULA scores were
      significantly lower with patients in the supine position when each physician was
      evaluated independently (p < 0.0001, for both). CONCLUSIONS: Placing patients in
      a supine position for cerumen removal results in more favorable ergonomic
      positioning for the physician, thus reducing risk for work-related
      musculoskeletal disorders. This suggests that physicians should consider placing
      patients in the supine position for in-office otologic procedures. Further study
      is needed to investigate optimal ergonomic positioning for other common
      otolaryngology procedures.

PMID- 30106853
TI  - Spontaneous Canalith Jam and Apogeotropic Horizontal Canal Benign Paroxysmal
      Positional Vertigo: Considerations on a Particular Case Mimicking an Acute
      Vestibular Deficit.
AB  - OBJECTIVE: Canalith jam refers to a condition caused by an otolithic clump
      blocked inside a semicircular canal, generally provoked by canalith repositioning
      procedure. We describe the first case of spontaneous canalith jam mimicking an
      acute vestibular deficit. PATIENT: We report the case of an 82-year-old woman who
      suffered a sudden episode of persistent rotational vertigo with nausea and
      vomiting, not provoked by head movements. INTERVENTIONS: Videonystagmography
      revealed a horizontal right-beating spontaneous nystagmus, inhibited by visual
      fixation. Surprisingly, the positional test showed a direction changing
      apogeotropic horizontal nystagmus weaker in the left side, compatible with a left
      side horizontal canal canalolithiasis of the apogetropic type. Returning to the
      sitting position, a spontaneous nystagmus was observed again, not tilt sensitive.
      A left side caloric paresis was found. RESULTS: After performing liberatory
      maneuvers, the spontaneous nystagmus disappeared and a horizontal canal benign
      paroxysmal positional vertigo of geotropic type was documented. The canal paresis
      also disappeared. CONCLUSIONS: Canalith jam is rarely described and is overall
      observed as a repositioning manoeuvre complication, not as a mimicker of a
      vestibular neuritis. Furthermore, our case represents the first observation of a
      recurrent canalith jam and apogeotropic variant of horizontal canal benign
      paroxysmal positional vertigo.

PMID- 30106852
TI  - Electronic Health Record Use Among American Neurotology Society Members.
AB  - OBJECTIVE: To describe the use of electronic health records (EHR) among members
      of the American Neurotology Society (ANS). STUDY DESIGN: Cross-sectional.
      SETTING: Active ANS members in November 2017. INTERVENTION: Internet-based
      survey. MAIN OUTCOME MEASURE: Survey that assessed the use of EHR in practice,
      types of EHR programs, different elements of EHR employed, and respondents'
      satisfaction and efficiency with EHR. RESULTS: One hundred twenty-seven ANS
      members responded to the survey with 67 (52.8%) respondents working in academic
      practice and 60 (47.2%) respondents working in private practice. Epic was the
      most commonly used EHR with 89 (70.1%) respondents using this system. Among all
      respondents, 84 (66.1%) respondents reported their efficiency was reduced by EHR
      use, and there was an even split between respondents who reported they were
      satisfied versus dissatisfied with their EHR (~40% each). We found that younger
      members were more likely to feel EHR increased their efficiency compared with the
      older members (p = 0.04). In all other analyses, we found no significant
      difference in efficiency and satisfaction between age groups, practice settings,
      presence of residents or fellows, or specific EHR used. The main challenges
      reported by ANS members related to the EHR were increased time burden, poor user
      interface, lack of customizability, and the focus away from patients.
      CONCLUSIONS: The majority of ANS members felt their efficiency decreased as a
      result of EHR. These findings provide specific changes to the EHR that would
      improve efficiency and satisfaction among neurotologists.

PMID- 30106854
TI  - Evaluation of Outcome Variability Associated With Lateral Wall, Mid-scalar, and
      Perimodiolar Electrode Arrays When Controlling for Preoperative Patient
      Characteristics.
AB  - OBJECTIVE: Determine the impact of electrode array selection on audiometric
      performance when controlling for baseline patient characteristics. STUDY DESIGN:
      Retrospective evaluation of a prospective cochlear implant (CI) database (January
      1, 2012-May 31, 2017). SETTING: Tertiary Care University Hospital. PATIENTS:
      Three hundred twenty-eight adult CI recipients. INTERVENTIONS/MAIN OUTCOMES
      MEASURED: Hearing outcomes were measured through unaided/aided pure tone
      thresholds and speech recognition testing before and after cochlear implantation.
      All reported postoperative results were performed at least 6 months after CI
      activation. All device manufacturers were represented. RESULTS: Of the 328
      patients, 234 received lateral wall (LW) arrays, 46 received perimodiolar (PM)
      arrays, and 48 received mid-scalar (MS) arrays. Patients receiving PM arrays had
      significantly poorer preoperative earphone and aided PTAs and SRTs, and aided
      Consonant-Nucleus-Consonant(CNC) word and AzBio +10 SNR scores compared with
      patients receiving LW arrays (all p <= 0.04), and poorer PTAs and AzBio +10 SNR
      scores compared with MS recipients (all p <= 0.02). No preoperative audiological
      variables were found to significantly differ between MS and LW patients. After
      controlling for preoperative residual hearing and speech recognition ability in a
      hierarchical multiple regression analysis, no statistically significant
      difference in audiological outcomes was detected (CNC words, AzBio quiet, or
      AzBio +10 SNR) among the three electrode array types (all p > 0.05). CONCLUSION:
      While previous studies have demonstrated superior postoperative speech
      recognition scores in LW electrode array recipients, these differences lose
      significance when controlling for baseline hearing and speech recognition
      ability. These data demonstrate the proclivity for implanting individuals with
      greater residual hearing with LW electrodes and its impact on postoperative
      results.

PMID- 30106855
TI  - Direct Acoustic Cochlear Implants Lead to an Improved Speech Perception Gap
      Compared to Conventional Hearing Aid.
AB  - OBJECTIVES: The objectives of this study was to evaluate the aided speech
      perception in quiet of direct acoustic cochlear implant (DACI) patients and the
      speech perception gap in comparison with hearing aid users. STUDY DESIGN:
      Retrospective comparative study. SETTING: Tertiary referral center. PATIENTS:
      Adults with moderate-to-severe mixed hearing loss who have been implanted with a
      DACI and fitted with a processor for at least 6 months. INTERVENTION(S):
      Comparison of aided monosyllabic word scores and speech perception gap of 59 DACI
      implanted ears speech perception gap with published data on 208 ears aided with a
      conventional hearing aid (HA) divided into four different hearing loss groups
      between 35 and 75 dB HL. MAIN OUTCOME MEASURE(S): Aided monosyllabic word score,
      predicted maximum monosyllabic word recognition score (PBmax) and speech
      perception gap. RESULTS: In terms of aided speech perception, DACI patients with
      cochlear reserves between 45 and 65 dB HL have a significant advantage compared
      with conventional HA users. A speech perception gap of 11% points for DACI and
      21% points for conventional HAs were determined and an approximation of PBmax is
      achieved by 52% of the DACI patients compared with only 36% of the HA users.
      CONCLUSIONS: For patients with moderate-to-severe inner ear hearing loss between
      45 and 65 dB HL, better speech perception in quiet is obtained with the DACI
      system. Compared with conventional hearing aids, speech performance with the DACI
      is closer to the maximally possibly score PBmax.

PMID- 30106856
TI  - Adolescent Obesity Is an Independent Risk Factor for Sensorineural Hearing Loss:
      Results From the National Health and Nutrition Examination Survey 2005 to 2010.
AB  - OBJECTIVE: We investigated the hypothesis that childhood obesity is a risk factor
      for sensorineural hearing loss (SNHL) independent of other metabolic risk
      factors. STUDY DESIGN: A complex, multistage, stratified geographic area design
      for collecting representative data from noninstitutionalized US population.
      METHODS: A total of 5,638 adolescents between age 12 and 19 from the NHANES
      database (2005-2010) were studied. Subjects with body mass index >= 95th
      percentile were classified as obese. SNHL was defined as average pure-tone
      greater than 15 dB HL for 0.5, 1, and 2 kHz or 3, 4, 6, and 8 kHz in at least 1
      ear. Multivariable logistic regression models assessed incident hearing loss odds
      across obese patients in comparison with normal weight individuals (5th-85th
      percentile). Multivariable models included age, sex, socioeconomic status, race,
      smoke exposure, high density lipoprotein level, triglyceride level, elevated
      blood pressure measurement, hemoglobin A1C level, and C-reactive protein level.
      RESULTS: The rate of SNHL was 21.5% in obese and 13.44% in normal weight
      adolescents (p < 0.0001). In multivariable analyses, obesity was associated with
      1.73-fold increase in the odds of SNHL (95% CI: 1.25-2.40, p value = 0.006).
      Potentially confounding and mediating factors had minimal effect on the odds of
      SNHL in obese study participants (OR range of 1.69-1.75, all p values <= 0.01).
      CONCLUSIONS: Obesity is associated with higher prevalence of SNHL in adolescents
      independent of other potential risk factors. Future longitudinal investigations
      and mechanistic studies are warranted.

PMID- 30106858
TI  - In Memoriam: Sheldon Baum 1927-2018: Erratum.

PMID- 30106857
TI  - The Prognostic Value of 18F-FDG PET/CT in Monitoring Chemotherapy in Ovarian
      Cancer Both at Initial Diagnosis and at Recurrent Disease.
AB  - Published experiences related to the prognostic relevance of negative or positive
      FDG PET/CT in patients treated for ovarian cancer for progression-free survival
      and overall survival are typically heterogeneous retrospective analyses. Several
      points have been well defined, these are as follows: (a) there is a correlation
      between FDG tumor uptake and prognosis; (b) ovarian cancer patients treated by
      neoadjuvant or adjuvant chemotherapy can be divided into responders with
      reduction in tumor FDG uptake during and after treatment and nonresponders where
      tumor FDG uptake remains stable or increases after treatment;

PMID- 30106859
TI  - Hepatic Involvement of IgG4-Related Disease Presenting as Multiple Hypermetabolic
      Masses on FDG PET/CT.
AB  - A 45-year-old man was found with multiple hepatic masses in CT/MR, suggesting
      liver metastases of unknown origin. F-FDG PET/CT showed several hypermetabolic
      masses in the liver; patchy increased uptake in the pancreas; and FDG-avid lymph
      nodes in the neck, axilla, and mediastinum. Histopathology with biopsy revealed
      enriched IgG4-positive lymphoplasmacytic cells infiltrating in the liver,
      pancreas, and lymph nodes, which confirmed the diagnosis of IgG4-related disease.
      The lesions were diminished on follow-up PET/CT 3 months after treatment with
      prednisone. This case illustrated that multifocal FDG-avid hepatic mass might be
      the involvement of IgG4-related disease, which should be differentiated from
      malignancies.

PMID- 30106860
TI  - Re: Response Assessment of 223Ra Treatment: Should a Fluorocholine PET/CT Be
      Performed?

PMID- 30106861
TI  - Demonstration of Tubercular "Abdominal Cocoon" (Sclerosing Encapsulating
      Peritonitis) in 18F-FDG PET/CT.
AB  - Sclerosing encapsulating peritonitis also called as abdominal cocoon is a less
      understood condition mostly due to idiopathic causes and sometimes secondary to
      tuberculosis or peritoneal dialysis. This report describes the typical features
      of "abdominal cocoon" on F-FDG PET/CT in a young woman, which was later diagnosed
      to be secondary to tuberculosis. Because the early features of this unusual
      entity are often nonspecific, high clinical suspicion along with understanding of
      the typical radiological/PET/CT features of this intriguing entity may guide the
      physician in ruling out the secondary treatable causes like tuberculosis, as
      noted in the index case.

PMID- 30106862
TI  - 99mTc-MDP Bone Scan and 18F-FDG PET/CT Imaging of Multiple Extraskeletal
      Osteosarcomas.
AB  - Extraskeletal osteosarcomas are uncommon entities in clinical practice, which
      account for 1% to 2% of all soft tissue sarcomas. We here reported a case of
      multiple extraskeletal osteosarcomas and nuclear medicine imaging findings of
      this disease in Tc-MDP bone scan as well as F-FDG PET/CT.

PMID- 30106863
TI  - Multiple Heterotopic Ossification of the Intestine Detected by 99mTc-MDP Bone
      Scan in a Patient With Primary Peritoneal Cancer.
AB  - Heterotopic ossification is a rare phenomenon that refers to formation of bone
      outside the skeletal system. We present a 61-year-old woman who suffered from
      peritoneal cancer surgery 2 years ago, referred for Tc-MDP bone scan because of
      higher serum CA-125 level, which showed multiple intense tracer activities in her
      abdominal and pelvic region without other abnormalities. SPECT/CT revealed the
      activities were loaded in the intestine but not in the bone. A wait-and-see
      policy was adopted because of no abdominal discomfort. After 1-year follow-up,
      another bone scintigraphy showed the tracer uptake was significantly decreased.

PMID- 30106864
TI  - Prediction of Occult Lymph Node Metastasis Using Tumor-to-Blood Standardized
      Uptake Ratio and Metabolic Parameters in Clinical N0 Lung Adenocarcinoma.
AB  - PURPOSE: We aimed to investigate whether the tumor-to-blood SUV ratio (SUR) and
      metabolic parameters of F-FDG uptake could predict occult lymph node metastasis
      (OLM) in clinically node-negative (cN0) lung adenocarcinoma. MATERIALS AND
      METHODS: We retrospectively reviewed 157 patients with cN0 lung adenocarcinoma
      who underwent both preoperative F-FDG PET/CT and surgical resection with the
      systematic lymph node dissection. The SUVmax, SUVmean, MTV, and total lesion
      glycolysis (TLG) of the primary tumor was measured on the PET/CT workstation.
      SURmax, SURmean, and TLGsur were derived from each of them divided by descending
      aorta SUVmean. These PET parameters and clinicopathological variables were
      analyzed for OLM. RESULTS: In our study, OLM was detected in 31 (19.7%) of 157
      patients. Significantly higher values of tumor size, SUVmax, SUVmean, MTV,
      TLGsuv, SURmax, SURmean, and TLGsur were found in patients with OLM. In receiver
      operating characteristic curve analysis, the optimal cutoff values of the above
      parameters were 29.50, 4.38, 2.45, 6.37, 44.13, 5.30, 1.86, and 28.24,
      respectively. The multivariate analysis showed that TLGsur (odds ratio, 1.024; P
      = 0.002) was the most potent associated factor for the prediction of OLM in cN0
      lung adenocarcinoma. CONCLUSIONS: TLGsur showed the most powerful predictive
      performance than the other PET parameters for the prediction of OLM in cN0 lung
      adenocarcinoma. This normalized volumetric parameter would be helpful in
      selection of sublobar resection or aggressive tailored treatments in patients
      with cN0 lung adenocarcinoma.

PMID- 30106865
TI  - Predictors of Severe Clinical Course in Children With Carbon Monoxide Poisoning.
AB  - OBJECTIVE: Carbon monoxide (CO) is a gas, which is produced by incomplete
      combustion of hydrocarbon-containing substances, and causes significant tissue
      and organ damage in the common event of CO poisoning. This study aims to evaluate
      the demographic, clinical, and laboratory characteristics of patients diagnosed
      with CO poisoning in the emergency department and to determine the factors
      associated with severe course in the acute phase of poisoning. METHODS: A total
      of 331 patients diagnosed with CO poisoning in Hacettepe University Children's
      Hospital, Pediatric Emergency Unit, between January 2004 and March 2014 were
      included in the study. Their demographic characteristics, presenting complaints,
      physical examination findings, Glasgow Coma Scale scores, carboxyhemoglobin,
      leukocyte, hemoglobin, troponin T, pH and lactate levels, type of treatment
      (normobaric or hyperbaric oxygen), intensive care unit admissions, and outcome of
      poisoning were investigated. RESULTS: Ninety-three patients were given hyperbaric
      oxygen. Fifty-one patients were admitted to the pediatric intensive care unit, 18
      patients have had a severe clinical course, and 6 patients have died. The risk
      factors associated with severe disease course were determined to be low Glasgow
      Coma Scale score, high leukocyte count, and high troponin T levels at
      presentation. CONCLUSIONS: Glasgow Coma Scale score, leukocyte count, and
      troponin T level may be beneficial in predicting clinical outcomes and tailoring
      therapy in children with CO poisoning.

PMID- 30106866
TI  - Adverse Drug Event-Related Admissions to a Pediatric Emergency Unit.
AB  - OBJECTIVES: The objectives of this study were to analyze adverse drug events
      (ADEs) related to admissions to a pediatric emergency unit and to identify the
      associated risk factors. METHODS: This was a prospective study. Demographic data
      and details of medications were collected for each patient admitted. Case studies
      were performed by clinical pharmacists and the clinical team to discuss whether
      the admission was due to an ADE and to characterize the ADE. Multivariate
      logistic regression was used for statistical analysis. RESULTS: In total, 1708
      pediatric patients were included in this study. Adverse drug events were the
      cause of hospital admission in 12.3% of the studied population. The majority of
      patients presenting with an ADE were in the age group of 0 to 5 years (61.6%),
      had a mean +/- SD age of 4.9 +/- 3.9 years, were female (51.2%), were Caucasian
      (72.0%), and had infectious disorders (49.3%). High frequencies of medication
      errors (68.8%), use of drugs to treat respiratory disorders (27.7%), and ADEs of
      mild severity (75.3%) were reported. The risk of being admitted to the pediatric
      emergency unit for any ADE increased in cases of neurological (odds ratio [OR],
      4.63; 95% confidence interval [CI], 2.38-8.99), dermatological (OR, 3.16; 95% CI,
      1.93-5.18), and respiratory (OR, 3.02; 95% CI, 1.89-4.83) disorders. CONCLUSIONS:
      A high frequency of ADE-related admissions to the pediatric emergency unit was
      observed. The risk of being admitted to the pediatric emergency unit for any ADE
      increased in cases of neurological, dermatological, and respiratory disorders.
      Clinical pharmacists play an important role in the identification of ADEs and the
      education of child caregivers and health care providers concerning pediatric
      medication.

PMID- 30106867
TI  - Pediatric Transport Practices Among Prehospital Providers.
AB  - OBJECTIVE: There are nearly 1000 annual ambulance crashes within the United
      States involving pediatric patients. In 2012 National Highway Traffic Safety
      Administration/US Department of Transportation released Best-Practice
      Recommendations for the Safe Transportation of Children in Emergency Ground
      Ambulances. The aim of our study was to measure emergency medical services (EMS)
      providers' knowledge and opinions of how to safely transport pediatric patients.
      In addition, we aimed to gather information on barriers to safe pediatric
      transport. METHODS: Members of 1 urban and 2 suburban EMS agencies completed an
      anonymous survey that assessed level of training, years of experience, exposure
      to pediatric patients, knowledge of best practices, and opinions about barriers
      to safe transport of pediatric patients. RESULTS: A total of 114 EMS providers
      answered the survey. Sixty-three percent were basic life support providers who
      had more than 10 years of experience in EMS. Ninety-six percent reported that
      they transported 0 to 5 pediatric patients per week. Twenty percent reported
      being trained on pediatric safe transport practices. Thirty-two percent of
      providers reported that personnel did not drive faster when transporting a sick
      pediatric patient. Eighty-six percent reported that it was unsafe to transport a
      child on a parent's lap, but 27% reported that it was appropriate to transport a
      newborn on the stretcher with mom. Thirty-eight percent were comfortable
      identifying proper restraint system/seat for pediatric patients, and only 35%
      were comfortable installing/using these devices. Provider-reported barriers to
      safe transport were identified. DISCUSSION: Our survey demonstrates that despite
      published best practices for the safe transport of children, many providers are
      unfamiliar with the safest way to transport these patients. In addition, we
      identified several existing barriers that may contribute to unsafe practices.

PMID- 30106868
TI  - A Randomized Single-Blinded Simulation-Based Trial of a Novel Method for Fluid
      Administration to a Septic Infant.
AB  - OBJECTIVES: For children presenting in shock, American College of Critical Care
      Medicine guidelines recommend 3 boluses of intravenous fluids during initial
      resuscitation, but these are often not met. This study aims to compare a novel
      device LifeFlow, to established manual methods for rapid fluid delivery in a
      simulated environment. METHOD: This single-blinded randomized trial was conducted
      in a level 1 pediatric trauma center emergency department. Fifty-four
      participants were paired and randomized to one of the following methods:
      push/pull, pressure bag, or LifeFlow. The teams were presented with a
      standardized simulation-based case and asked to resuscitate a 10-kg patient in
      decompensated shock. We used a demographic survey to study provider variables,
      recordings of the simulation and fluid delivery to independently establish rate
      and accuracy, and the National Aeronautical and Space Administration Task Load
      Index to assess workload. RESULT: All 54 participants completed the assigned
      tasks, and no significant differences were found among the demographics of
      participants. The primary outcome (mean rate of fluid administration) differed
      significantly between the 3 techniques, LifeFlow being the fastest (65.29
      mL/min). The composite National Aeronautical and Space Administration Task Load
      Index score (30; P = 0.184) was lowest for the LifeFlow. Significant differences
      were seen among the correlation coefficient comparing the estimated to the actual
      volume of fluid for each method, pressure bag being the highest (0.66), followed
      by push-pull (0.54) and LifeFlow (0.31). CONCLUSIONS: LifeFlow allowed for faster
      fluid administration rate and thus could be the preferred technique for rapid
      fluid resuscitation in pediatrics patients. Further investigations should explore
      the reproducibility of these results using this device in real patients in
      multiple centers.

PMID- 30106869
TI  - True Versus False Bacteremia in Infants and Children Less Than 3 Years of Age.
AB  - OBJECTIVE: The objective of this study was to examine patient history as well as
      clinical and laboratory features associated with true bacteremia versus false
      bacteremia in previously healthy febrile children ages 0 to 36 months in the era
      of polyvalent conjugate pneumococcal immunization. METHODS: Using retrospective
      chart review, we examined history, physical examination, and laboratory
      characteristics associated with true and false bacteremia. We included subjects
      under 3 years old, with a positive blood culture obtained in the emergency
      department or clinic from July 2011 to July 2013, and fever defined as a
      temperature of greater than or equal to 100.4 degrees F by history or
      examination. We excluded those with a previously known underlying disease process
      that could increase the risk for positive blood culture, for example,
      immunodeficiency, cancer, cystic fibrosis, or significant skin disorders such as
      severe eczema, as well as patients with any indwelling central line, shunt, or
      other implanted device, or recent hospitalization for a febrile illness. RESULTS:
      Thirty subjects (24%) had true bacteremia, and 97 (76%) had false bacteremia. In
      the multivariable logistic regression analysis, exposure to sick contacts (odds
      ratio, 0.1; 95% confidence interval, 0.01-0.6; P = 0.01) and increased hours to
      positive blood culture (odds ratio, 0.8; 95% confidence interval, 0.8-0.9; P <
      0.001) remained significant factors associated with false bacteremia. Age,
      maximum reported temperature, and reported days of fever were not associated with
      true bacteremia. CONCLUSIONS: We found that previously healthy children with true
      bacteremia are more likely to grow bacteria faster on blood culture and lack
      exposure to sick contacts than children with false bacteremia.

PMID- 30106870
TI  - Comparison of 4 Pediatric Intraosseous Access Devices: A Randomized Simulation
      Study.
AB  - BACKGROUND: Obtaining intravascular access can be challenging or even impossible
      in several clinical situations. As an alternative, medications and fluids can be
      administered via the intraosseous (IO) route, which is a well-tolerated and
      established alternative, especially in the emergency setting. METHODS: Seventy
      five novice physicians participated in this randomized simulation study. After a
      single educational session and 6 months without any clinical application,
      participants were asked to identify the correct puncture site and obtain IO
      access using 3 widely used mechanical devices (BIG Pediatric, Arrow EZ-IO, NIO
      Pediatric) and a manual device (Jamshidi needle) on a pediatric manikin and
      turkey bone, respectively. RESULTS: Sixty-eight participants correctly identified
      the puncture site and performed IO cannulations. First placement attempt success
      rate was similar with mechanical devices (NIO Pediatric, 100%; Arrow EZ-IO, 97%;
      and BIG Pediatric, 90%), whereas was only 43% using the manual Jamshidi device.
      Also, procedure time was much faster using mechanical devices (ranging between 18
      and 23 seconds) compared with the manual Jamshidi device (34 seconds).
      CONCLUSIONS: Although the efficacy of devices was demonstrated in simulated
      environment in novice users, further studies are needed to assess the efficacy
      and safety of devices in clinical comparative settings. With more experienced
      users, the success rate may differ considerably as compared with naive users.

PMID- 30106871
TI  - Hypothermia as an Outcome Predictor Tool in Pediatric Trauma: A Propensity
      Matched Analysis.
AB  - OBJECTIVE: Hypothermia is an independent risk factor for mortality in adult
      trauma patients. Two small studies have shown similar results in pediatric trauma
      patients. Temperature is not included in any pediatric trauma assessment scores.
      This study sought to compare mortality and various descriptive outcomes between
      pediatric hypothermic and normothermic trauma patients. METHODS: Data were
      obtained from the National Trauma Database from 2009 to 2012. Patients meeting
      inclusion criteria were stratified by presence of isolated head injury, head
      injury with multiple trauma, and absence of head injury. These groups were then
      subdivided into hypothermic (temperature <=36 degrees C) and normothermic groups.
      We used propensity score matching to 1:1 match hypothermic and normothermic
      patients. Mortality, neurosurgical interventions, endotracheal intubation, blood
      transfusion, length of stay, laparotomy, thoracotomy, conversion of cardiac
      rhythm, and time receiving mechanical ventilation were evaluated. RESULTS: Data
      from 3,011,482 patients were obtained. There were 414,562 patients who met the
      inclusion criteria. In all patients meeting inclusion criteria, hypothermia was a
      significant risk factor in all outcomes measured. Following stratification and
      1:1 matching, in all groups, hypothermia was associated with increased mortality
      (P < 0.0001), increased rate of endotracheal intubation (P < 0.0002), increased
      need for blood transfusion (P < 0.0025), and conversion of cardiac rhythm (P <
      0.0027). CONCLUSION: Hypothermia has been shown to be a significant prognostic
      indicator in the pediatric trauma patient with further potential application.
      Future studies are indicated to evaluate the incorporation of hypothermia into
      the Pediatric Trauma Score not only to help predict injury severity and mortality
      but also to improve appropriate and expeditious patient transfer to pediatric
      trauma centers and potentially facilitate earlier intervention.

PMID- 30106872
TI  - Veterinary-Prescribed Buprenorphine Ingestion in a 2-Year-Old Girl.
AB  - INTRODUCTION: Ingestion of buprenorphine by young children is on the rise and can
      lead to life-threatening consequences and death. Exposure most often occurs when
      a child acquires the medication intended for adult use. However, buprenorphine is
      also prescribed by veterinarians and may be sent home, typically in non-child
      resistant packaging, to be administered to the family pet. CASE: A previously
      healthy 2-year-old girl weighing 11.36 kg was found with a 1-mL syringe
      containing 0.6 mg/mL of buprenorphine in her mouth. The syringe had been in a
      plastic bag provided to the family by their veterinarian for the family dog. She
      was hospitalized for 24 hours but remained asymptomatic and was discharged
      healthy. This type of exposure to buprenorphine has not previously been described
      in the literature. CONCLUSIONS: Having this unsecured medication in the home
      increases the potential risk of exposure for young children and associated health
      consequences. Pediatricians should be aware of the potential dangers that
      veterinary pharmaceuticals can pose and educate parents about proper storage of
      medications. In addition, veterinarians should take extra precautions when
      dispensing these medications to pet owners with children.

PMID- 30106873
TI  - Part II: Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) for
      Types of Infections and Organ Dysfunction Endpoints.
AB  - ABSTACT: While the clinical definitions of sepsis and recommended treatments are
      regularly updated, a systematic review has not been done for pre-clinical models.
      To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis
      modeling reviewed the 260 most highly cited papers between 2003 and 2012 using
      sepsis models to create a series of recommendations. This Part II report provides
      recommendations for the types of infections and documentation of organ injury in
      pre-clinical sepsis models. Concerning the types of infections, the review showed
      that the cecal ligation and puncture model was used for 44% of the studies while
      40% injected endotoxin. Recommendation #8 (numbered sequentially from part I):
      endotoxin injection should not be considered as a model of sepsis; live bacteria
      or fungal strains derived from clinical isolates are more appropriate.
      Recommendation #9: microorganisms should replicate those typically found in human
      sepsis. Sepsis-3 states that sepsis is life-threatening organ dysfunction caused
      by a dysregulated host response to infection, but the review of the papers showed
      limited attempts to document organ dysfunction. Recommendation #10: organ
      dysfunction definitions should be used in pre-clinical models. Recommendation
      #11: not all activities in an organ?system need to be abnormal to verify organ
      dysfunction. Recommendation #12: organ dysfunction should be measured in an
      objective manner using reproducible scoring systems. Recommendation #13: not all
      experiments must measure all parameters of organ dysfunction, but investigators
      should attempt to fully capture as much information as possible. These
      recommendations are proposed as "best practices" for animal models of sepsis.

PMID- 30106874
TI  - Part I: Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS) for
      Study Design And Humane Modeling Endpoints.
AB  - Pre-clinical animal studies are mandatory before new treatments can be tested in
      clinical trials. However, their use in developing new therapies for sepsis has
      been controversial because of limitations of the models and inconsistencies with
      the clinical conditions. In consideration of the revised definition for clinical
      sepsis and septic shock (Sepsis-3), a Wiggers-Bernard Conference was held in
      Vienna in May 2017 to propose standardized guidelines on pre-clinical sepsis
      modeling. The participants conducted a literature review of 260 most highly cited
      scientific articles on sepsis models published between 2003 and 2012. The review
      showed, for example, that mice were used in 79% and euthanasia criteria were
      defined in 9% of the studies. Part I of this report details the recommendations
      for study design and humane modeling endpoints that should be addressed in sepsis
      models. The first recommendation is that survival follow-up should reflect the
      clinical time course of the infectious agent used in the sepsis model.
      Furthermore, it is recommended that therapeutic interventions should be initiated
      after the septic insult replicating clinical care. To define an unbiased and
      reproducible association between a new treatment and outcome, a randomization and
      blinding of treatments as well as inclusion of all methodological details in
      scientific publications is essential. In all pre-clinical sepsis studies, the
      high standards of animal welfare must be implemented. Therefore, development and
      validation of specific criteria for monitoring pain and distress, and euthanasia
      of septic animals, as well as the use of analgesics are recommended. A set of
      four considerations is also proposed to enhance translation potential of sepsis
      models. Relevant biological variables and co-morbidities should be included in
      the study design and sepsis modeling should be extended to mammalian species
      other than rodents. Additionally, the need for source control (in case of a
      defined infection focus) should be considered. These recommendations and
      considerations are proposed as "best practices" for animal models of sepsis that
      should be implemented.

PMID- 30106877
TI  - Ineffectiveness of Repeated Intravenous Ketamine Infusions in Treatment-Resistant
      Depression After a Post-Ketamine Relapse: Time for a Rethink?

PMID- 30106876
TI  - The Effect of Body Weight Changes on Total Plasma Clozapine Concentrations
      Determined by Applying a Statistical Model to the Data From a Double-Blind Trial.
AB  - PURPOSE/BACKGROUND: Some therapeutic drug monitoring studies suggest that
      increased weight is associated with small increases in clozapine concentrations.
      The goal of this study was to reanalyze a US double-blind study using a
      sophisticated statistical model to test whether weight gains from baseline or
      increases in percentage of body fat from baseline, computed from a published
      equation, are associated with increased total plasma clozapine concentrations
      after controlling for the effects of smoking and sex. METHODS/PROCEDURES: Using
      data from a multidosage randomized double-blind US clozapine trial previously
      published, a random intercept linear model of steady-state total plasma clozapine
      concentrations was fitted to 424 concentrations from 47 patients.
      FINDINGS/RESULTS: After adjusting for sex and smoking, (1) a 1-kg gain in body
      weight during clozapine treatment was significantly associated with a 1.4%
      increase in total plasma clozapine concentrations (95% confidence interval = 0.55
      to 2.3) and (2) a 1-point increase in percentage of body fat during clozapine
      treatment was significantly associated with a 5.4% increase in total clozapine
      concentration (2.5 to 8.3) in females and 1.4% (-1.1 to 4.0) in males.
      IMPLICATIONS/CONCLUSIONS: As hypothesized, weight increases during clozapine
      treatment, which probably reflect increases in fat tissue, were associated with
      increases in total plasma concentrations. Pending further replication in other
      samples, it seems likely that clozapine may deposit in body fat and that this may
      decrease clozapine clearance. This change may be small in most patients but may
      be clinically relevant in females with major gains in body fat.

PMID- 30106875
TI  - Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS): An
      International Expert Consensus Initiative for Improvement of Animal Modeling in
      Sepsis.
AB  - Preclinical animal studies precede the majority of clinical trials. While the
      clinical definitions of sepsis and recommended treatments are regularly updated,
      a systematic review of preclinical models of sepsis has not been done and clear
      modeling guidelines are lacking. To address this deficit, a Wiggers-Bernard
      Conference on preclinical sepsis modeling was held in Vienna in May, 2017. The
      goal of the conference was to identify limitations of preclinical sepsis models
      and to propose a set of guidelines, defined as the "Minimum Quality Threshold in
      Preclinical Sepsis Studies" (MQTiPSS), to enhance translational value of these
      models. A total of 31 experts from 13 countries participated and were divided
      into six thematic Working Groups: Study Design, Humane modeling, Infection types,
      Organ failure/dysfunction, Fluid resuscitation, and Antimicrobial therapy
      endpoints. As basis for the MQTiPSS discussions, the participants conducted a
      literature review of the 260 most highly cited scientific articles on sepsis
      models (2002-2013). Overall, the participants reached consensus on 29 points; 20
      at "recommendation" and nine at "consideration" strength. This Executive Summary
      provides a synopsis of the MQTiPSS consensus. We believe that these
      recommendations and considerations will serve to bring a level of standardization
      to preclinical models of sepsis and ultimately improve translation of preclinical
      findings. These guideline points are proposed as "best practices" for animal
      models of sepsis that should be implemented. To encourage its wide dissemination,
      this article is freely accessible on the Intensive Care Medicine Experimental and
      Infection journal websites. In order to encourage its wide dissemination, this
      article is freely accessible in Shock, Infection, and Intensive Care Medicine
      Experimental.

PMID- 30106878
TI  - A Case of Hypersexuality Probably Associated With Lurasidone.

PMID- 30106879
TI  - Treatment of Risperidone-Associated Hyperprolactinemia With Aripiprazole.

PMID- 30106880
TI  - Evaluating the Effect of Coenzyme Q10 Augmentation on Treatment of Bipolar
      Depression: A Double-Blind Controlled Clinical Trial.
AB  - BACKGROUND: Bipolar disorder (BPD) is a chronic and recurrent mood disorder
      characterized by episodes of mania, hypomania, and major depression. Based on
      available evidence, mitochondrial dysfunction, oxidative stress, and inflammation
      have important roles in the pathophysiology of bipolar depression. More
      specifically, it seems that coenzyme Q10 (CoQ10), a mitochondrial modulator, as
      well as an antioxidant and anti-inflammatory agent, might be effective in
      modulating these pathophysiological pathways. Accordingly, the aim of this study
      was to investigate whether and to what extent, compared with placebo, adjuvant
      CoQ10 might improve symptoms of depression in patients with BPD. METHODS: A total
      of 69 patients with BPD with a current depressive episode were randomly assigned
      either to the adjuvant CoQ10 (200 mg/d) or to the placebo group. Standard
      medication consisting of mood stabilizers and antidepressants was consistent 2
      months prior and during the study. Depression severity for each patient was
      assessed based on the Montgomery-Asberg Depression Rating Scale scores at
      baseline, fourth week, and eighth week of the study. RESULTS: Symptoms of
      depression decreased over time in both groups. Compared with the placebo group,
      adjuvant CoQ10 to a standard medication improved symptoms of depression after 8
      weeks of treatment. In addition, at the end of the study, it turned out that more
      responders were observed in the CoQ10 group, compared with the placebo group.
      CoQ10 had minimal adverse effects and was well tolerated. CONCLUSIONS: The
      present pattern of results suggests that among patients with BPD, compared with
      placebo, adjuvant CoQ10 probably because of its antioxidant and anti-inflammatory
      properties can improve symptoms of depression over a period of 8 weeks.

PMID- 30106881
TI  - Tranylcypromine Plus Amitriptyline for Electroconvulsive Therapy-Resistant
      Depression: A Long-Term Study.
AB  - BACKGROUND: Few therapeutic options are available for patients with
      electroconvulsive therapy-resistant major depressive disorder (ECT-r MDD),
      leaving a substantial proportion of this population beyond treatment
      possibilities. The combination of monoamine oxidase inhibitors and tricyclic
      antidepressants could be a potential strategy for managing ECT-r MDD, and the
      specific association of amitriptyline and tranylcypromine may offer additional
      tolerability advantages. Although promising, in our knowledge, no studies have
      examined until now the effectiveness of this combination in ECT-r MDD. METHODS:
      We report a retrospective cohort of 31 patients with ECT-r MDD treated in an open
      label fashion with the combination of amitriptyline and tranylcypromine. RESULTS:
      Overall, 80.6% of the sample met response criteria at the end of the first 12
      weeks of treatment. Seventy-six percent (19 of 25) of the responders were
      followed for a mean of 9.37 +/- 3.86 years. During this follow-up period, none of
      the patients had a recurring depressive episode. The combination was well
      tolerated, whereas minor adverse effects were common, and no severe or life
      threatening events were reported throughout the study. CONCLUSIONS: These
      findings indicate that the combination tranylcypromine and amitriptyline is a
      potentially safe and effective candidate for future investigation in the
      treatment and long-term maintenance of ECT-r MDD.

PMID- 30106883
TI  - Efficacy of Sertraline in Patients With Major Depressive Disorder Naive to
      Selective Serotonin Reuptake Inhibitors: A 10-Week Randomized, Multicenter,
      Placebo-Controlled, Double-Blind, Academic Clinical Trial.
AB  - PURPOSE: The aim of this study was to assess the efficacy and safety of
      sertraline compared with placebo in a good clinical practice trial conducted with
      major depressive disorder patients naive to selective serotonin reuptake
      inhibitors. METHODS: This was a 10-week randomized, multicenter, placebo
      controlled, double blind, superiority trial. Adult patients diagnosed with major
      depressive disorder (Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition criteria), total score of 19 to 36 in the 17-item Hamilton
      Depression Rating Scale (HAMD-17), were randomly allocated to sertraline (n = 39)
      or placebo (n = 38). Each patient received a fixed dose of sertraline 50 mg/d or
      placebo for 4 weeks. Afterward a flexible dose up to 200 mg/d was allowed if
      needed. The primary efficacy end point was clinical response defined as 50% score
      reduction in HAMD-17 at 10 weeks relative to baseline. Supplementary analysis was
      performed on HAMD-17 score change from baseline. FINDINGS: The clinical response
      favored sertraline (72% vs 32%; relative risk, 2.27; 95% confidence interval,
      1.37-3.78; P = 0.0006). A linear mixed model showed arm * time interaction was
      significant (likelihood ratio test chi on 7 df = 48.42, P < 0.0001). The HAMD-17
      change score favored sertraline from week 8 onwards. The most frequent adverse
      events in the sertraline arm were headache, diarrheas, and weight loss.
      IMPLICATIONS: In this trial, the benefit of sertraline compared with placebo
      appeared later than usual. The therapeutic process with a close doctor-patient
      relationship throughout the trial and the effect expectancy due to a new
      treatment might explain the response delay. TRIAL REGISTRATION: RPCEC, ID no.
      00000128.

PMID- 30106884
TI  - Switching From Tobacco Smoking to Electronic Cigarettes and the Impact on
      Clozapine Levels.

PMID- 30106885
TI  - Erratum - Updated Affiliation for Two Articles by Dr Lin, et al.

PMID- 30106886
TI  - Integrating HIV and Maternal, Neonatal and Child Health Services in Rural Malawi:
      An Evaluation of the Implementation Processes and Challenges: Erratum.

PMID- 30106889
TI  - Spectrally resolved thermal emission of atmospheric gases measured by laser
      heterodyne spectrometry.
AB  - The demonstration of thermal infrared quantum cascade laser heterodyne
      spectrometry to resolve local thermodynamic equilibrium molecular emission lines
      from earth's atmospheric constituents is presented. The instrument is described,
      as well as the early steps towards radiometric calibration. Room temperature
      ethylene emission line measurements carried out in the laboratory are used to
      validate the instrument. High-resolution (0.02  cm-1) emission lines from
      atmospheric carbon dioxide and water vapor are then recorded in a zenith-looking
      configuration and compared to a radiative transfer model and ideal instrument
      model expectations.

PMID- 30106888
TI  - Bounding the outcome of a two-photon interference measurement using weak coherent
      states.
AB  - The interference of two photons at a beam splitter is at the core of many quantum
      photonic technologies, such as quantum key distribution or linear-optics quantum
      computing. Observing high-visibility interference is challenging because of the
      difficulty of realizing indistinguishable single-photon sources. Here, we perform
      a two-photon interference experiment using phase-randomized weak coherent states
      with different mean photon numbers. We place a tight upper bound on the expected
      coincidences for the case when the incident wavepackets contain single photons,
      allowing us to observe the Hong-Ou-Mandel effect. We find that the interference
      visibility is at least as large as 0.995-0.013+0.005.

PMID- 30106887
TI  - High Interleukin-37 (IL-37) Expression and Increased Mucin-Domain Containing-3
      (TIM-3) on Peripheral T Cells in Patients with Rheumatoid Arthritis.
AB  - BACKGROUND Anti-inflammatory mediators such as mucin-domain containing-3 (TIM-3)
      and IL-37 play an important role in the regulation of Th1-mediated immunity. This
      study was designed to investigate the proportions of various T cell subsets and
      monocytes in the peripheral blood of rheumatoid arthritis (RA) patients, as well
      as the level of TIM-3 on these cells and serum cytokine levels. MATERIAL AND
      METHODS We enrolled 59 RA patients and 46 age- and sex-matched healthy controls
      in this study. The proportion of T cells and TIM-3 expression on these T cells
      were determined by flow cytometry. Cytokine levels in serum were determined by
      ELISA. RESULTS Compared with the healthy controls, the proportions of CD3+CD4+ T
      cells and CD3+CD4+CD25+CD127low T cells in the peripheral blood were
      significantly higher in RA patients. However, RA patients had significantly lower
      proportions of CD3+CD8+ T cells and CD3+CD4-CD8- T cells. TIM-3 was highly
      expressed on CD3+CD4+, CD3+CD8+, CD3+CD4+CD25+CD127low, and CD3+CD4-CD8- T cells,
      as well as CD14+ monocytes, in RA patients. Nevertheless, no correlation between
      TIM-3 level and an RA disease activity score of 28 was found. The elevated serum
      levels of IL-6 and IL-37 were positively correlated with tumor necrosis factor
      alpha (TNF-alpha). CONCLUSIONS Both pro-inflammatory cytokines (TNF-alpha and IL
      6) and anti-inflammatory mediators (TIM-3 and IL-37) simultaneously contribute to
      the pathogenesis of RA. TIM-3 and IL-37 may be used as potential biomarkers of
      active RA.

PMID- 30106890
TI  - Full characterization of spatial coregistration errors and spatial resolution in
      spectral imagers.
AB  - For multi- and hyperspectral imagers, the integrity of the spectral information
      depends critically on the spatial coregistration between bands. There is at
      present no commonly accepted way to fully specify coregistration performance.
      This Letter shows how a relatively simple measurement technique can be used to
      form sharp images of the point spread function (PSF) in all bands, yielding
      information about spatial coregistration, as well as spatial resolution. A
      previously proposed metric is applied to characterize coregistration in terms of
      PSF similarity between bands. Resolution is characterized by ensquared energy.
      Two commercial hyperspectral cameras with nominally similar specifications are
      compared, and turn out to have large differences in their actual performance. The
      results, and the relative simplicity of the measurement, suggest that the method
      is suitable as a standardized performance test.

PMID- 30106891
TI  - High-Q Fano resonances via direct excitation of an antisymmetric dark mode.
AB  - The engineering of metal-insulator-metal metasurfaces (MSs) displaying sharp
      spectral features based on Fano-type interference between a symmetric bright mode
      and an antisymmetric dark mode is reported. The proposed mechanism for direct
      excitation of antisymmetric mode avoids the necessity of mode hybridization
      through near-field coupling. Modeling and experimental results bring evidence
      that such MSs operating in the microwave or terahertz domains provide greater
      flexibility for Fano resonance engineering and provide strong enhancement of the
      spectral selectivity factor. It is shown that the occurring Fano resonance
      interference is related to the broken eigenmode orthogonality in open systems and
      is independent of hybridization mechanism.

PMID- 30106892
TI  - Ultrafast optical imaging at 2.0  MUm through second-harmonic-generation-based
      time-stretch at 1.0  MUm.
AB  - The performance of ultrafast time-stretch imaging at long wavelengths (beyond 1.5
      MUm) has suffered from low detection sensitivity due to the increasing loss of
      optical dispersive fibers. Here, we report an ultrafast optical imaging system
      with a line scan rate of ~19  MHz at the 2.0-MUm wavelength window by combining
      second-harmonic generation (SHG) with the highly sensitive time-stretch detection
      at 1.0 MUm. In this imaging system, the sample is illuminated by the pulsed laser
      source at 2.0 MUm in the spectrally encoding manner. After SHG, the encoded
      spectral signal at 2.0 MUm is converted to 1.0 MUm and then mapped to the time
      domain through a highly dispersive fiber at 1.0 MUm, which provides a superior
      dispersion-to-loss ratio of ~53  ps/nm/dB, ~50  times larger than that of the
      standard fibers at 2.0 MUm (typically ~1.1  ps/nm/dB). These efforts make it
      possible for time-stretch technology not only being translated to longer
      wavelengths, where unique optical absorption contrast exists, but also
      benefitting from the high detection sensitivity at shorter wavelengths.

PMID- 30106893
TI  - Arbitrarily spin-orientated and super-resolved focal spot.
AB  - In this Letter, we propose a facile approach for achieving a robust focal spot
      bearing both super-resolution and arbitrary spin orientation. Toward this aim, we
      meticulously devise a structured incident light consisting of three sorts of
      beams, which can be produced definitely by the superposition of a radially
      polarized beam and an azimuthally polarized beam. Based on the vectorial
      diffraction integral and spin density theory, such newly configurable beams are
      tightly focused and isotropically interfered in a 4pi microscopic configuration
      to create three polarized field components perpendicular to each other beyond the
      diffraction limit, thus enabling us to yield a super-resolved focal spot
      possessing spatial spin axis. By further willfully adjusting the amplitude
      factors of the reconstituent fields, the photonic spin direction can be freely
      tunable. The demonstrated results in this Letter may hold great potential for the
      spin photonics.

PMID- 30106895
TI  - Modal area statistics for transverse Anderson localization in disordered optical
      fibers.
AB  - We introduce the mode-area probability density function (MA-PDF) as a powerful
      tool to study transverse Anderson localization (TAL), especially for highly
      disordered optical fibers. The MA-PDF encompasses all the relevant statistical
      information on TAL; it relies solely on the physics of the disordered system and
      is independent of the shape of the external excitation. We explore the scaling of
      the MA-PDF with the transverse dimensions of the system and show that it
      converges to a terminal form for structures considerably smaller than those used
      in experiments, hence substantially reducing the computational cost to study TAL.

PMID- 30106894
TI  - Self-healing of space-time light sheets.
AB  - Space-time (ST) wave packets are diffraction-free, dispersion-free pulsed beams
      whose propagation invariance stems from correlations introduced into their spatio
      temporal spectra. We demonstrate here experimentally and computationally that ST
      light sheets exhibit self-healing properties upon traversing obstacles in the
      form of opaque obstructions. The unscattered fraction of the wave packet retains
      the spatio-temporal correlations and, thus, propagation invariance is maintained.
      The scattered component does not satisfy the requisite correlation and thus,
      undergoes diffractive spreading. These results indicate the robustness of ST wave
      packets and their potential utility for deep illumination and imaging in
      scattering media, such as biological tissues.

PMID- 30106896
TI  - 20  kW class high-beam-quality CW laser amplifier chain based on a Yb:YAG slab at
      room temperature.
AB  - A continuous-wave-operation laser amplifier chain consisting of three multi
      concentration-doped Yb:YAG slab gain modules (GMs) at room temperature is
      presented. The output power of 22.3 kW with the beam quality of 3.3 times the
      diffraction limit is achieved from this chain. To the best of our knowledge,
      based on a Yb:YAG slab at room temperature, the highest power to date while
      maintaining excellent beam quality laser output. An extraction efficiency of 36%
      from the single slab GM is obtained and can be further enhanced to 46% by
      optimizing the parameters of GM. These results have confirmed that the Yb:YAG
      slab has an excellent scaling performance and is suitable for the development of
      high-average-power lasers.

PMID- 30106897
TI  - Hybrid diagnostic for optimizing domain size and resolution of 3D measurements.
AB  - This Letter reports a hybrid three-dimensional (3D) visualization approach for
      turbulent flows at the kilohertz range. The approach, named scanning volumetric
      laser induced fluorescence (SVLIF), combines 3D tomography with scanning to
      significantly enhance spatial resolution of 3D measurements in a given domain (or
      equivalently, to enlarge the domain size under a given resolution) compared to
      past tomographic approaches. The SVLIF technique (1) divides a large measurement
      domain into smaller sub-domains, (2) performs 3D tomographic measurement in each
      sub-domain by scanning the excitation laser pulses across them consecutively, and
      (3) combines the measurements in all sub-domains to form a final measurement.
      This hybrid approach enables the conversion of temporal resolution into spatial
      resolution or domain size to optimize 3D measurements in a wider design space. In
      this work, the SVLIF was demonstrated and validated at a scanning rate of 1.86
      kHz in a volume of 38.4  mm*26.5  mm*25.2  mm with 7.1 million voxels,
      representing a ~5 times enhancement in the number of voxels or the domain size
      compared to past tomographic techniques.

PMID- 30106898
TI  - Hybrid Monte Carlo simulation with ray tracing for fluorescence measurements in
      turbid media.
AB  - We present a hybrid Monte Carlo simulation method with geometrical ray tracing
      (hMC-GRT) to model fluorescence excitation and detection in turbid media by
      optical imaging or spectroscopy systems employing a variety of optical
      components. hMC-GRT computational verification was achieved via reflectance and
      fluorescence simulations on epithelial tissue models in comparison with a
      standard Monte Carlo code. The mean difference between the two simulations was
      less than 5%. hMC-GRT experimental verification employed depth-sensitive steady
      state fluorescence measurements using an aspherical lens on two-layered tissue
      phantoms. hMC-GRT predictions agreed well with experimental results, achieving
      less than 3.5% error for measurements at the phantom surface. Verification
      results demonstrate that the hMC-GRT simulation has the potential to become a
      useful computational toolbox for designing tissue fluorescence imaging and
      spectroscopy systems. In addition, the hMC-GRT approach enables a wide variety of
      applications for computational modeling of fluorescence in turbid media. The
      source codes are available at https://github.com/ubioptronics/hMC-GRT.

PMID- 30106899
TI  - Continuous every-single-shot carrier-envelope phase measurement and control at
      100  kHz.
AB  - With the emergence of high-repetition-rate few-cycle laser pulse amplifiers aimed
      at investigating ultrafast dynamics in atomic, molecular, and solid-state
      science, the need for ever faster carrier-envelope phase (CEP) detection and
      control has arisen. Here we demonstrate a high-speed, continuous, every-single
      shot measurement and fast feedback scheme based on a stereo above-threshold
      ionization time-of-flight spectrometer capable of detecting the CEP and pulse
      duration at a repetition rate of up to 400 kHz. This scheme is applied to a 100
      kHz optical parametric chirped pulse amplification few-cycle laser system,
      demonstrating improved CEP stabilization and allowing for CEP tagging.

PMID- 30106900
TI  - Observation of short wavelength infrared (SWIR) Cherenkov emission.
AB  - Cherenkov emission induced by external beam radiation from a clinical linear
      accelerator has been shown in preclinical molecular imaging and clinical imaging.
      The broad spectrum Cherenkov emission should have a short wavelength infrared
      (SWIR, 1000-1700 nm) component, as predicted theoretically. To the best of our
      knowledge, this Letter is the first experimental observation of this SWIR
      Cherenkov emission induced by external beam radiation. The measured spectrum of
      SWIR Cherenkov emission matches the theoretical prediction, with a fluence rate
      near one-third of the visible and near-infrared red emissions (Vis-NIR, 400-900
      nm). Imaging in water-based phantoms and biological tissues indicates that there
      is a sufficient fluence rate for radiotherapy dosimetry applications. The spatial
      resolution is improved approximately 5.3 times with SWIR Cherenkov emission
      detection versus Vis-NIR Cherenkov emission, which provides some improvement in
      the potential for higher resolution Cherenkov emission dosimetry and molecular
      sensing during clinical radiotherapy by imaging with SWIR wavelengths.

PMID- 30106901
TI  - Efficient terahertz and infrared Smith-Purcell radiation from metal-slot
      metasurfaces.
AB  - We demonstrate that when a charged particle moves on top of a metal-slot
      metasurface consisting of metallic slot resonators, strong Smith-Purcell
      electromagnetic (EM) radiation can be produced at resonant frequency. By
      adjusting the period of the metasurface, the resonant (or working) frequency can
      be tuned from gigahertz to terahertz and infrared regions. Since the EM field is
      localized in the slots rather than at the metal surface, the metasurfaces are
      found to exhibit a very low absorption loss ratio (<1%) in low working
      frequencies (<1  THz). Although it becomes larger in high frequencies (>1  THz),
      the loss ratio remains relatively low (<12%). In addition, a nonlinear
      relationship is also uncovered between the resonant frequency and the reciprocal
      of the period. Our results could benefit the construction of efficient, compact
      terahertz, and infrared free-electron light sources.

PMID- 30106902
TI  - Few-layer Ti3C2Tx (T = O, OH, or F) saturable absorber for a femtosecond bulk
      laser.
AB  - Few-layered titanium carbide (Ti3C2Tx), a novel two-dimensional (2D) Van der
      Waals material in the MXene family, was fabricated with a liquid-phase method and
      applied as a saturable absorber for a continuous-wave mode-locked femtosecond
      bulk laser. Pulses as short as 316 fs with a repetition rate of 64.06 MHz and
      maximum output power of 0.77 W were achieved at the central wavelength of 1053.2
      nm, demonstrating the first known, to the best of our knowledge, application of
      MXene in an all-solid-state laser. Considering the flexible band gap for
      different surface functional groups of Ti3C2Tx, these results may promote the
      development of ultrafast photonics and further applications of 2D optoelectronic
      layered materials in the infrared and mid-infrared regions.

PMID- 30106903
TI  - Spectral pulse shaping of a 5  Hz, multi-joule, broadband optical parametric
      chirped pulse amplification frontend for a 10  PW laser system.
AB  - We present a broadband optical parametric chirped pulse amplification (OPCPA)
      system delivering 4 J pulses at a repetition rate of 5 Hz. It will serve as a
      frontend for the 1.5 kJ, <150  fs, 10 PW laser beamline currently under
      development by a consortium of National Energetics and Ekspla. The spectrum of
      the OPCPA system is precisely controlled by arbitrarily generated waveforms of
      the pump lasers. To fully exploit the high flexibility of the frontend, we have
      developed a 1D model of the system and an optimization algorithm that predicts
      suitable pump waveform settings for a desired output spectrum. The OPCPA system
      is shown to have high efficiency, a high-quality top-hat beam profile, and an
      output spectrum demonstrated to be shaped consistently with the theoretical
      model.

PMID- 30106904
TI  - Natural convection induced by an optically fabricated and actuated microtool with
      a thermoplasmonic disk.
AB  - Two-photon polymerization was employed for fabricating microtools amenable to
      optical trapping and manipulation. A disk feature was included as part of the
      microtools and further functionalized by electron-beam deposition. The
      nanostructured gold layer on the disk facilitates off-resonant plasmonic heating
      upon illumination with a laser beam. As a consequence, natural convection
      characterized by the typical toroidal shape resembling that of Rayleigh-Benard
      flow can be observed. A velocity of several MUm.s-1 is measured for 2 MUm
      microspheres dispersed in the surroundings of the microtool. To the best of our
      knowledge, this is the first time that thermoplasmonic-induced natural convection
      is experimentally demonstrated using a mobile heat source.

PMID- 30106905
TI  - Retrieval of weak x-ray scattering using edge illumination.
AB  - X-ray phase contrast imaging provides additional modes of image contrast compared
      to conventional attenuation-based x-ray imaging, thus providing additional
      structural and functional information about the sample. The edge-illumination
      (EI) technique has been used to provide attenuation, refraction, and scattering
      contrast in both biological and non-biological samples. However, the retrieval of
      low scattering signals by fitting a single Gaussian remains problematic,
      principally due to the inability of the EI system to achieve perfect dark-field
      illumination. We present a new retrieval method that fits three Gaussians, which
      successfully overcomes this limitation, and provide examples of the retrieval of
      such signals in highly absorbing, weakly scattering samples.

PMID- 30106906
TI  - Observation of microscale nonparaxial optical bottle beams.
AB  - We predict and experimentally observe three-dimensional microscale nonparaxial
      optical bottle beams based on the generation of a caustic surface under
      revolution. Such bottle beams exhibit high contrast between the surrounding
      surface and the effectively void interior. Via caustic engineering, we can
      precisely control the functional form of the high-intensity surface to achieve
      microscale bottle beams with longitudinal and transverse dimensions of the same
      order of magnitude. Although, in general, the phase profile at the input plane
      can be computed numerically, we find closed-form expressions for bottle beams
      with various types of surfaces both in the real and in the Fourier space.

PMID- 30106907
TI  - Temperature-dependent persistent luminescence of SrAl2O4:Eu2+, Dy3+, Tb3+: a
      strategy of optical thermometry avoiding real-time excitation.
AB  - A new strategy of optical thermometry is realized by long persistent luminescence
      phosphor SrAl2O4:Eu2+, Dy3+, Tb3+ (SAEDT). Under different temperatures, SAEDT
      shows bright afterglow emissions after cessation of the UV excitation. The
      afterglow color of the SAEDT sample is blue at 60 K and gradually changed into
      green at 240 K. The normalized afterglow spectra at different temperatures give a
      dramatic change of fluorescence intensity ratio between the blue band and the
      green band. Not only has this material exhibited a high absolute sensitivity and
      relative sensitivity for temperature sensing, but it also has the great advantage
      of eliminating the heating effect due to avoidance of real-time direct
      excitation.

PMID- 30106908
TI  - Phase transformation induced reversible modulation of upconversion luminescence
      of WO3:Yb3+, Er3+ phosphor for switching devices.
AB  - The upconverting luminescence properties of phosphors are dependent on the hosts.
      In this work, the WO3:Yb3+, Er3+ phosphor was prepared, and the reversible phase
      transformation from the WO3 to the WO2 was obtained by alternating the sintering
      in a reducing atmosphere or in air. The influence of reversible phase
      transformation on the upconversion luminescence was investigated first. The
      WO3:Yb3+, Er3+ phosphor exhibits the visible upconversion luminescence, while no
      upconversion luminescence was observed in the WO2:Yb3+, Er3+ phosphor. The
      reversible modulation of upconversion luminescence of the WO3:Yb3+, Er3+ phosphor
      retains the excellent reproducibility, exhibiting the potential applications in
      data storage and optical switches.

PMID- 30106909
TI  - 400-Gbit/s QPSK free-space optical communicationlink based on four-fold
      multiplexing of Hermite-Gaussian or Laguerre-Gaussian modes by varying both modal
      indices.
AB  - We experimentally demonstrate the four-fold multiplexing of Hermite-Gaussian
      (HGmn) or Laguerre-Gaussian (LGlp) modes to achieve a 400 Gbit/s quadrature-phase
      shift-keyed (QPSK) free-space optical communication link. In this experiment,
      both modal indices for the HG and LG modes are simultaneously utilized to achieve
      a larger potential orthogonal modal space. Moreover, we also investigate and
      compare the effects of aperture size, lateral displacement, and rotation on the
      system. We measure the degree of performance degradation due to the following:
      (1) a receiver aperture with a limited size causes power loss and crosstalk for
      both HG and LG modes; (2) a lateral misalignment between the transmitter and
      receiver which leads to crosstalk for LG modes, but might not affect HG0n or HGm0
      modes due to axial symmetry; and (3) a rotational misalignment between the
      transmitter and receiver which causes crosstalk for the HG modes, but does not
      tend to affect the LG modes due to azimuthal symmetry.

PMID- 30106910
TI  - Strain-assisted femtosecond inscription of phase-shifted gratings.
AB  - Two slightly shifted gratings are inscribed, one over the other, while exploiting
      fiber strain in a single-mode fiber. The inscription is done with a near-infrared
      femtosecond laser, a phase mask, and a cylindrical focusing lens. The first fiber
      Bragg grating (FBG) is inscribed under normal fiber tension, while the second
      overlapping FBG is inscribed under higher fiber tension. The transmission
      spectrum of the complex structure is similar to that of a phase-shifted grating,
      yet the fabrication process is much faster and simpler compared to other standard
      methods. A high-quality phase-shifted grating with two -30  dB transmission dips,
      a 25 dB transmission peak, and <50  pm transmission bandwidth is achieved. We
      observe polarization-dependent transmission in the phase-shifted gratings.

PMID- 30106911
TI  - Soliton-like pulse propagation in a normal dispersive liquid-core optical fiber.
AB  - Soliton-like pulse propagation, where the pulse intensity profile is conserved,
      except for its trailing edge, is found in a normal dispersive CS2-core optical
      fiber by a computer simulation. During propagation, it is found that the chirp of
      a pulse arising from the delayed nonlinear response compensates for the chirp
      arising from the second-order dispersion near the pulse peak position and the
      pulse experiences a negative frequency shift and a negative temporal shift. The
      effects of the instantaneous nonlinear response on the soliton-like pulse
      propagation are also evaluated, and the calculated spectrum agreed well with the
      experimental spectrum.

PMID- 30106912
TI  - Controllable trapping and releasing of nanoparticles by a standing wave on
      optical waveguides.
AB  - Based on the balance between the scattering force and the trapping force of an
      evanescent field of a standing wave on silicon waveguides, we propose a structure
      for controllable trapping and releasing of nanoparticles, which can act as pause
      operation for nanoparticle flow control. The design is realized by the cascade of
      an optical switch with a structure of a ring-assisted Mach-Zehnder interferometer
      (RAMZI) and a Sagnac loop reflector which connects to one output of the switch.
      Through thermal tuning, with a tiny refractive index change of 4.3*10-4 on a ring
      resonator, the output of a RAMZI can be switched between two ports. As for the
      release state of the nanoparticle flow, the light is guided to the port without a
      reflector. There is no standing wave or traps formed on a waveguide. Therefore,
      the scattering force dominates, which drives particles moving forward to output
      ports. Otherwise, for trapping a state, the light will be reflected by the Sagnac
      loop and form a stationary standing wave which provides an array of traps for
      nanoparticles. Most importantly, the structure can switch its state to trap or
      sequentially release particles without losing the control of samples which, to
      the best of our knowledge, has not been realized before. With the statistical
      description of particle motion, the balance between trapping and releasing is
      distinguished by the trapping time and tuned by reflectance. The feasibility of
      our design is verified using the three-dimensional finite-difference time domain
      and Maxwell stress tensor methods. Our structure possesses the merits of high
      compactness and time effectiveness and, thereby, it is highly suitable for on
      chip optical manipulation of nanoparticle flow control, which brings great
      potential in integrated on-chip optofluidics.

PMID- 30106913
TI  - Twisted EM beams with structured correlations.
AB  - The possibility of restructuring the spectral density of a random light beam up
      to three times along the propagation path in free space is demonstrated. This can
      be achieved by prescribing special correlations and different twist factors (by
      magnitude and/or direction) in the two mutually orthogonal electric field
      components in the source plane. We also show that the degree of polarization of
      such a light beam can rotate or not on propagation.

PMID- 30106914
TI  - Energy enhancement of the target surface electron by using a 200 TW sub
      picosecond laser.
AB  - One order of magnitude energy enhancement of the target surface electron beams
      with central energy at 11.5 MeV is achieved by using a 200 TW, 500 fs laser at an
      incident angle of 72 degrees  with a prepulse intensity ratio of 5*10-6. The
      experimental results demonstrate the scalability of the acceleration process to
      high electron energy with a longer (sub-picosecond) laser pulse duration and a
      higher laser energy (120 J). The total charge of the beam is 400+/-20  pC(E>2.7 
      MeV). Such a high orientation and mono-energetic electron jet would be a good
      method to solve the problem of the large beam divergence in fast ignition schemes
      and to increase the laser energy deposition on the target core.

PMID- 30106915
TI  - Hollow complementary omega-ring-shaped metamaterial modulators with dual-band
      tunability.
AB  - In this Letter, we report two kinds of metamaterial modulators based on hollow
      complementary omega-ring-shaped (HCOmega) structures, which are fabricated on
      parylene-C thin film with high flexibility and can realize dual-band amplitude
      tunability. The first type of structure (HCOmega-I) consists of identical unit
      cells along a similar direction, achieving different tunability under different
      compression directions but suffering from polarization dependence. To investigate
      the effect of unit cell direction on polarization direction, the unit cells in
      the HCOmega-I device are rotated by 90 degrees  in sequence to form a symmetrical
      type of structure (HCOmega-II), which successfully produces reverse dual-band
      variation of transmission with good polarization independence. These two
      developed flexible modulators with varied tunable ability will have a promising
      application in terahertz detection, sensing, and imaging.

PMID- 30106916
TI  - Magneto-optical effects in hyperbolic metamaterials.
AB  - Highly anisotropic metal-dielectric structures reveal unique dispersion
      properties providing new optical effects. Here we study experimentally linear
      optical and magneto-optical response of arrays of plasmonic gold nanorods and
      similar structures complemented by a thin nickel film. We show that both types of
      structures reveal distinct optical features expected for hyperbolic media and
      associated with the epsilon-near-zero (ENZ) and epsilon-near-pole (ENP) points.
      In the case of Ni-containing nanocomposites, we observe linear magneto-optical
      effects in transmission through the structure, increasing in the vicinity of
      these points. This observation reveals an important role of the local field
      enhancement in a hyperbolic medium associated with ENZ and ENP dispersion points
      in the appearance of magneto-optical activity of magnetic hyperbolic
      metamaterials.

PMID- 30106918
TI  - Micro-lensing-induced line shapes in a single-mode cold-atom-hollow-core-fiber
      interface.
AB  - We report on the observation of strong transmission line shape alterations in a
      cold-atom-hollow-core-fiber interface. We show that this can lead to a
      significant overestimation of the assigned resonant optical depth for high atom
      densities. By modeling light beam propagation in an inhomogeneous dispersive
      medium, we attribute the observations to micro lensing in the atomic ensemble in
      combination with the mode selection of the atom-fiber interface. The approach is
      confirmed by studies of Rydberg electromagnetically induced transparency line
      shapes.

PMID- 30106917
TI  - Mutual interaction of red blood cells assessed by optical tweezers and scanning
      electron microscopy imaging.
AB  - The adhesion of red blood cells (RBC) has been studied extensively in frame of
      cell-to-cell interaction induced by dextran macromolecules, whereas the data are
      lacking for native plasma solution. We apply optical tweezers to investigate the
      induced adhesion of RBC in plasma and in dextran solution. Two hypotheses, cross
      bridges and depletion layer, are typically used to describe the mechanism of cell
      interaction; however, both mechanisms need to be confirmed experimentally. These
      interactions in fact are very much dependent on the size and concentration of
      dextran and proteins in plasma. The results show that in different dextran
      solutions, the interaction of adhering RBC agrees well with the quantitative
      predictions obtained based on the depletion-induced cells adhesion model, whereas
      the migrating cross-bridges model is more appropriate for plasma. Despite the
      different mechanisms of RBC interaction in a mixture of dextran with the size
      ranges and volume fraction proportional to plasma proteins, the dependence of RBC
      adhering tends to be close to the cross-bridges model. The induced aggregation of
      RBC in the dextran solutions and in native plasma are observed by direct
      visualization utilizing scanning electron microscopy.

PMID- 30106919
TI  - Ruby fluorescence-enabled ultralong lock-on time high-gain gallium arsenic
      photoconductive semiconductor switch.
AB  - We report a new type of photoconductive semiconductor switch (PCSS), consisting
      of a semi-insulating gallium arsenic (GaAs) substrate and a front-bonded ruby
      crystal. The 532 nm laser pulses from an Nd-YAG laser incident on the front
      surface of the ruby crystal. A portion of the laser pulse passes through the
      crystal and reaches the GaAs substrate, and the remaining portion of the laser
      pulse is absorbed by the ruby crystal. This results in the emission of 694 nm
      fluorescent light. Furthermore, a portion of emitted fluorescent light also
      reaches the GaAs substrate. The high-fluence 532 nm short laser pulse with a
      pulse width around several nanoseconds is used to trigger the PCSS entering the
      high-gain nonlinear mode, whereas the low-fluence long-lifetime (on the order of
      a millisecond) 694 nm fluorescent light is used to maintain the lock-on time.
      Thus, an ultralong lock-on time on the order of millisecond is achieved, which is
      3 orders of magnitude longer than a typical lock-on time of high-gain GaAs PCSS.

PMID- 30106920
TI  - Controlled generation of ultrafast vector vortex beams from a mode-locked fiber
      laser.
AB  - We report on a new class of mode-locked fiber lasers that allow direct creation
      of ultrafast vector vortex beams at arbitrary positions on the higher-order
      Poincare sphere. The on-demand generation of space-variant polarization patterns
      was realized by controlling geometric phases inside the laser resonator to map
      polarization to orbital angular momentum. Thanks to the special cavity design,
      the required intracavity manipulation of the geometric phase imposed no
      disturbance on the passively mode-locked operation, thus demonstrating robust and
      flexible switching of vectorial modes with an 8.5 ps pulse duration. Analytical
      expressions were deduced to model the generated cylindrically symmetric
      polarization profiles, which are in agreement with experimental observations. The
      presented fiber laser would constitute a compact light source for producing
      ultrafast pulses in high-purity structured modes, which may find broad
      applications in classical and quantum optics.

PMID- 30106921
TI  - Watt-level narrow-linewidth fibered laser source at 852 nm for FIB application.
AB  - We realize a 1 W all-fibered polarized compact and robust laser source at 852 nm
      for laser cooling of cesium atoms. The architecture is based on the sum-frequency
      generation of 1540 and 1908 nm lasers, realized through a periodically poled
      lithium niobate waveguide with a conversion efficiency of 40%. A linewidth of 20
      kHz is achieved with the development of a distributed feedback fiber laser at
      1908 nm. The operation of this laser source is demonstrated on a focused ion beam
      (FIB) experiment based on cold cesium atoms.

PMID- 30106922
TI  - Thin-rod Yb:YAG amplifiers for high average and peak power lasers.
AB  - The concept of a high-power thin-rod Yb:YAG laser amplifier with high-brightness
      diode pumping was proposed. The principle of the amplifier parameter variation
      aimed at achieving an efficient signal gain at different power levels was
      developed. Three versions of thin-rod gain modules were implemented, where small
      and strong signal gains were studied experimentally. The ultrafast laser system
      with high average power (28 W) and high pulse energy (2.5 mJ) was created on the
      basis of the unique thin-rod gain modules.

PMID- 30106923
TI  - Dynamic tuning of the Q factor in a photonic crystal nanocavity through photonic
      transitions.
AB  - Photonic devices based on a high-Q cavity are commonly constrained by narrow
      operation bandwidth, slow charging, and releasing speed. Here, we analytically
      and numerically demonstrate that this limitation can be broken via dynamically
      tuning the Q factors of a single nanocavity and driving controllable photonic
      transitions between a low-Q cavity mode and an ultrahigh-Q mode by temporal
      refractive index modulations inside a multimode cavity. During this dynamic
      process, the bandwidth of signal light is also reversibly compressed. As a
      result, the fundamental link between the photon lifetime and the operation
      bandwidth is broken, and a delay-bandwidth product of ~76 is achieved, which is
      far greater than that of the usual optical resonator systems. This approach may
      pave the way for dynamic control of on-chip all-optical information processing.

PMID- 30106924
TI  - Raman-assisted phase sensitive amplifier using a fiber Bragg grating-based
      tunable phase shifter.
AB  - A low-loss Raman-assisted phase sensitive amplifier (PSA) with a ~20  dB signal
      net gain is experimentally demonstrated. The amplitude and phase adjustment for
      PSA are achieved by using non-uniform Raman gain and a tunable fiber Bragg
      grating (FBG), respectively. The total component loss of the system is measured
      to be ~8  dB. By tuning the FBG central wavelength, (1) an up to 5.6 dB signal
      gain improvement is obtained; and (2) a ~4  dB receiver sensitivity enhancement
      is observed for 20 and 25 Gbaud quadrature phase shift keying signals and a 10
      Gbaud 16-quadrature amplitude modulation signal.

PMID- 30106925
TI  - Simultaneous generation of high-power, ultrafast 1D and 2D Airy beams and their
      frequency-doubling characteristics.
AB  - We report on a simple experimental scheme based on a pair of cylindrical lenses
      (convex and concave) of the same focal length and common optical elements,
      producing high power optical beams in 1D and/or 2D Airy intensity profiles with
      laser polarization as the control parameter. Using an ultrafast Yb-fiber laser at
      1064 nm of average power of 5 W in a Gaussian spatial profile and pulse width of
      ~180  fs, we have generated 1D and 2D Airy beams at an efficiency of 80% and 70%,
      respectively, and a pulse width of ~188 and ~190  fs, respectively. We have
      measured the transverse deflection rate of 1D and 2D beams to be ~5.0*10-5 1/mm
      and ~2.0*10-5 1/mm, respectively. Simply rotating the polarization state of the
      1D cubic phase modulated beam in the experiment, we can produce 1D and 2D Airy
      beams on demand. Using a 5 mm long bismuth borate (BiB3O6), we have also studied
      frequency-doubling characteristics of both 1D and 2D Airy beams. Like the 2D Airy
      beam, the 1D Airy beam also produces a frequency-doubled 1D Airy and an
      additional 1D spatial cubic structure. Like the Gaussian beams, we have observed
      the focusing dependence of conversion efficiency for both 1D and 2D Airy beams,
      producing green 1D and 2D Airy beams of output powers in excess of 110 and 150 mW
      for 3.4 and 2.8 W of fundamental power, respectively.

PMID- 30106926
TI  - In-fiber whispering-gallery mode microsphere resonator-based integrated device.
AB  - A novel in-fiber whispering-gallery mode (WGM) microsphere resonator-based
      integrated device is reported. It is fabricated by placing a silica microsphere
      into an embedded dual-core hollow fiber (EDCHF). Using a fiber tapering method, a
      silica microsphere can be placed and fixed in the transition section of the
      hollow core of the EDCHF. The transmitted light from the tapered-input single
      mode fiber is coupled into the embedded silica microsphere via the two suspended
      fiber cores, and hence effectively excites the WGMs. A Q-factor of 5.54*103 is
      achieved over the wavelength range of 1100-1300 nm. The polarization and
      temperature dependence of the in-fiber WGM microsphere resonator device is also
      investigated experimentally. This integrated photonics device provides greatly
      improved mechanical stability, compared with the traditional tapered fiber
      coupled WGM microresonator devices. Additional advantages include ease of
      fabrication, compact structure, and low cost. This novel in-fiber WGM resonator
      integrated device is ideally positioned to access a wide range of potential
      applications in optical sensing and microcavity lasing.

PMID- 30106927
TI  - Goos-Hanchen effect for Brillouin light scattering by acoustic phonons.
AB  - The lateral shift of an optical beam undergoing Brillouin light scattering on an
      acoustic wave (AW) in the total internal reflection geometry is studied
      theoretically. It is shown that the lateral shift depends on polarization
      (longitudinal or transversal) of the AW, as well as on the type of scattering
      process: a direct one, when the scattered wave undergoes a lateral shift at
      reflection from the interface, or a cascading one, when a fundamental frequency
      light beam is laterally shifted at reflection and then scattered on the AW.

PMID- 30106928
TI  - Graphene mode-locked femtosecond Alexandrite laser.
AB  - We report for the first time, to the best of our knowledge, graphene mode-locked
      operation of a femtosecond Alexandrite laser at 750 nm. A multipass-cavity
      configuration was employed to scale the output energy and to eliminate spectral/Q
      switching instabilities. By using a monolayer graphene saturable absorber, mode
      locking could be obtained. With 5 W of pump at 532 nm, nearly transform-limited,
      65 fs pulses with a time-bandwidth product of 0.319 were generated. The mode
      locked laser operated at a pulse repetition rate of 5.56 MHz and produced 8 mW
      output power, corresponding to a pulse energy and peak power of 1.4 nJ and 22 kW,
      respectively. These experiments further show that graphene can be used to
      initiate mode locking at wavelengths as low as 750 nm.

PMID- 30106929
TI  - Elastomer thin-film pressure sensor based on embedded photonic tunnel-junction
      arrays.
AB  - We propose an elastomer thin-film pressure sensor enabled by pressure-sensitive
      optical signals through vertical photonic tunnel-junction couplers. We provide
      the operation principle, design, fabrication, and test results from a 50 MUm
      thick polydimethylsiloxane sheet accommodating embedded vertical photonic tunnel
      junction couplers. The result with a 5 mm long device shows a differential
      optical power change that is ~140% of the incident power under moderate external
      pressure of ~40  kPa, thereby clearly demonstrating a robust pressure-sensing
      capability realized in a highly flexible, lightweight, transferrable, optically
      transparent, and bio-compatible thin-film material. Therefore, the proposed
      approach potentially enables versatile pressure and touch sensors for many
      applications in practice.

PMID- 30106930
TI  - Intensity noise in high-frequency range of an external cavity diode laser and its
      reduction by second harmonic generation.
AB  - Characteristics of intensity noise of optically pumped vertical-cavity surface
      emitting lasers and solid-state lasers, induced by the beating of the main lasing
      mode and non-lasing side modes and its reduction, have been reported in recent
      years. The mode beating noise of an external cavity diode laser composed of an
      electrically pumped edge-emitting laser diode chip is studied experimentally in
      this Letter. The noises due to the beating of the main mode with the first- to
      third-order side modes are observed, and multiple sub-peaks in the beating noise
      are measured. It is assumed that the new phenomena are coming from the enhanced
      four-wave mixing in the longer-active medium. Intensity noise reduction is also
      demonstrated by using the second harmonic generation of a beta barium borate
      crystal as a nonlinear absorber.

PMID- 30106931
TI  - Fast analysis method for stochastic optical reconstruction microscopy using
      multiple measurement vector model sparse Bayesian learning.
AB  - Compressed sensing (CS) can be used in fluorescence microscopy to improve the
      temporal resolution of stochastic optical reconstruction microscopy (STORM).
      Currently, most algorithms used in CS-STORM belong to the single measurement
      vector (SMV) model, where each super-resolution image is recovered individually
      from a raw frame, thereby prolonging the computational time. Here, we apply the
      multiple measurement vector (MMV) model CS algorithm to STORM, wherein all raw
      images are converted into a matrix and recovered by solving the simultaneous
      sparse recovery problem. We use the MMV model-based sparse Bayesian learning
      (SBL) algorithm to reconstitute the raw images of STORM, then compare its imaging
      resolution and run time with the SMV model CS algorithms. The simulated and
      experimentally recovered super-resolution images prove that the resolution of MMV
      model SBL (M-SBL) is comparable with the SMV model algorithm, while the run time
      is far less and decreases from several hours to several minutes. The high
      resolution and shorter reconstitution time make M-SBL a promising real-time image
      reconstruction method for CS-STORM.

PMID- 30106932
TI  - Pure-three-level Yb:GdCOB CW laser at 976  nm.
AB  - We present what is, to the best of our knowledge, the first pure-three-level
      Yb:Ca4GdO(BO3)3 (Yb:GdCOB) laser emitting at 976 nm based on the F5/22-F27/2
      transition, generally used for a quasi-three-level emission at 1032 nm. A maximum
      power of 782 mW at 976 nm has been achieved in continuous-wave (CW) operation
      pumped by a quasi-three-level Nd:SrLaAlO4 laser emitting at 902 nm. Moreover, a
      self-frequency-doubling CW blue laser has also been demonstrated with a maximum
      power of 133 mW at 488 nm.

PMID- 30106933
TI  - Manipulation of the spontaneous parametric down-conversion process in space and
      frequency domains via wavefront shaping.
AB  - The spontaneous parametric down-conversion (SPDC) source of entangled-photon
      pairs is important for applications in the quantum information process and
      quantum communication, but suffers from scattering by sample defect and air
      impurity. Here, we proposed an alternative scheme to manipulate the scattered
      SPDC process, where only a spatial light modulator was used to control the
      incident wavefront. The scheme was experimentally tested and also applied on the
      manipulation of photon pairs through the SPDC process with spectral control. This
      work proved the feasibility of manipulating nonlinear signals at quantum level
      with feedback-based wavefront shaping and also indicated applications in long
      distance quantum key distribution, quantum communications, and quantum imaging,
      especially in complex environments.

PMID- 30106934
TI  - Nanophotonic control of the color center emission from nanodiamonds.
AB  - Recently, the nitrogen vacancy (NV) center has emerged as a deterministic single
      photon source at room temperature. However, the presence of phonon sideband
      emission limits the use of NV centers in various quantum optical applications.
      Here we report a novel way to suppress the phonon sideband emission of NV centers
      aided with the enhancement of zero phonon line intensity using photonic crystals
      at room temperature. We study the photonic stop gap mediated charge state
      conversion in NV centers. The enhancement of phonon sideband emission from the
      same structures by implementing a different measurement geometry is also
      discussed. The studies open new avenues in studying the NV center-based quantum
      nanophotonics and biophotonics.

PMID- 30106935
TI  - Ultrasound-modulated optical tomography in scattering media: flux filtering based
      on persistent spectral hole burning in the optical diagnosis window.
AB  - Ultrasound-modulated optical tomography (UOT) is a powerful imaging technique to
      discriminate healthy from unhealthy biological tissues based on their optical
      signature. Among the numerous detection techniques developed for acousto-optic
      imaging, only those based on spectral filtering are intrinsically immune to
      speckle decorrelation. This Letter reports on UOT imaging based on spectral hole
      burning in Tm:YAG crystal under a moderate magnetic field (200G) with a well
      defined orientation. The deep and long-lasting holes translate into a more
      efficient UOT imaging with a higher contrast and faster imaging frame rate. We
      demonstrate the potential of this method by imaging calibrated phantom scattering
      gels.

PMID- 30106936
TI  - Simple-structured, subfemtosecond-resolution optical-microwave phase detector.
AB  - We demonstrate a simple all-fiber photonic phase detector that can measure the
      phase (timing) difference between an optical pulse train and a microwave signal
      with subfemtosecond resolution and -60  dB-level amplitude-to-phase conversion
      coefficient. It is based on passive phase biasing of a Sagnac loop by the
      intrinsic phase shift of a symmetric 3*3 fiber coupler. By eliminating the
      necessity of magneto-optic components or complex radio frequency (RF) electronics
      for phase biasing of the Sagnac loop, this phase detector has potential to be
      implemented as an integrated photonic device as well. When using this device for
      synchronization between a 250 MHz mode-locked Er-fiber laser and an 8 GHz
      microwave oscillator, the minimum residual phase noise floor reaches <-154 
      dBc/Hz (at 8 GHz carrier) with integrated root mean square (rms) timing jitter of
      0.97 fs [1 Hz-1 MHz]. The long-term rms timing drift and frequency instability
      are 0.92 fs (over 5000 s) and 4*10-19 (at 10,000 s averaging time), respectively.

PMID- 30106937
TI  - Phase-sensitivity-doubled surface plasmon resonance sensing via self-mixing
      interference.
AB  - Conventional phase-based surface plasmon resonance (SPR) sensing can achieve 10-8
      RIU, but commonly requires two-beam interference. It therefore leads to
      complexity in terms of utilized devices, poor anti-noise ability, and demand for
      fine working conditions. With these requirements imposed, conventional SPR
      sensing has difficulties in commercial use. In this Letter, we report a simple,
      compact, and phase-sensitivity-doubled self-mixing interference (SMI)-based SPR
      sensing approach. The reported approach employs SMI and, therefore, needs only
      one optical path, enabling the advantages of compactness and simplicity in
      experimental setup, and strong anti-vibration property. With the proposed setup,
      the phase of light from the prism to the sample changes twice. Consequently, the
      sensitivity of phase is doubled. For experimental demonstration, we monitor the
      refractive index change of NaCl solution by using the proposed technique. The
      experimental results coincide with the theoretical analysis and simulation
      results.

PMID- 30106938
TI  - Large Brillouin gain in Germania-doped core optical fibers up to a 98  mol%
      doping level.
AB  - Germanosilicate glasses are substantial materials in fiber optic technology that
      have allowed the control of optical properties such as numerical aperture,
      photosensitivity, dispersion, nonlinearity, and transparency toward mid-infrared.
      Here, we investigate stimulated Brillouin scattering in single-mode
      germanosilicate core fibers with increasing GeO2 content from 3.6 mol% up to 98
      mol%. Our results reveal a wide Brillouin frequency shift tunability over more
      than 3 GHz with a strong decrease down to 7.7 GHz at high GeO2 content owing to
      the low acoustic velocity, while the Brillouin linewidth significantly broadens
      up to 100 MHz beyond 50 mol% of GeO2 content. In addition, large Brillouin gain
      up to 6.5 times larger than in standard silica fibers is also reported by means
      of a pump-probe experiment.

PMID- 30106939
TI  - Crossing-free on-chip 2  *  2 polarization-transparent switch with signals
      regrouping function.
AB  - We propose and demonstrate an on-chip 2*2 polarization-transparent switch for
      simultaneously handling two-group polarization-division multiplexing (PDM)
      signals. By introducing the polarization-transparent power splitter/combiner
      (PPS/PPC), waveguide crossings such as those in conventional PDM switches can be
      avoided and, thus, the insertion losses and complexity of the device can be
      reduced. Furthermore, each input polarization tributary can be independently
      switched and routed thanks to the output selectivity of the PPS/PPC. Thus, not
      only a basic switch between the dual-group PDM signals, but also a precise four
      channel-signal regrouping can be achieved, enabling a complete and non-redundant
      switching functionality. A polarization extinction ratio larger than 15 dB with
      reasonable insertion losses is experimentally observed. Clear and open eye
      diagrams can be obtained with less than 1 dB power penalties for all the measured
      paths.

PMID- 30106940
TI  - Coherent perfect absorption in wedged organic thin films: a method to determine
      optical properties.
AB  - We investigate coherent perfect absorption in layered thin-film structures with
      organic small molecules as absorbing material. We focus on strongly asymmetric
      resonator structures, realized with a high-optical-quality dielectric-distributed
      Bragg reflector and a thermally evaporated wedged organic layer on top. The
      optical properties of these devices are systematically investigated by selective
      optical pumping and probing of the structure along the wedge. We show that phases
      and amplitudes of all waves and their balance relations can be tuned such that
      coherent perfect absorption is achieved, i.e., almost all incident radiation is
      absorbed within the thin organic layer. We show that such wedged structures on
      highly reflective dielectric mirrors can be used as a novel approach to measure
      optical dispersion relations of absorbing materials in a broad spectral range
      without requiring any specific a priori knowledge of the absorbing film.

PMID- 30106941
TI  - Trimming method for a high-yield manufacturing of high-efficiency diffraction
      gratings.
AB  - The tolerances in manufacturing of fully dielectric diffraction gratings based on
      the leaky-mode resonance in the -1st diffraction order can be challenging,
      especially if the grating design exhibits high diffraction efficiency (DE) only
      within a comparatively narrow spectral bandwidth. To gain improved control on the
      spectral bandwidth exhibiting high DE, we implemented a two-step etching approach
      within the fabrication process of the grating. First, a dry and anisotropic
      etching step was used for pre-shaping the grating, followed by iterative
      isotropic wet-etching steps using an alkaline solution (KOH) at a temperature of
      90 degrees C to adjust the maximum efficiency around the desired wavelength with
      high precision. This straightforward method gave us very good control on
      tailoring the DE as a function of the wavelength and led to the demonstration of
      DEs as high as 99.7+/-0.2% in the -1st diffraction order at a wavelength of 1030
      nm and of >99% in the wavelength range between 1020 and 1070 nm. The gratings
      were used as cavity end mirrors of an Yb:YAG thin-disk laser, generating an
      output power of 145 W in fundamental mode operation (M2<1.1).

PMID- 30106943
TI  - PT symmetry and antisymmetry by anti-Hermitian wave coupling and nonlinear
      optical interactions.
AB  - Light propagation in systems with anti-Hermitian coupling, described by a spinor
      like wave equation, provides a general route for the observation of antiparity
      time (PT) symmetry in optics. Remarkably, under a different definition of parity
      operator, a PT symmetry can be found as well in such systems. Such symmetries are
      ubiquitous in nonlinear optical interactions and are exemplified by considering
      modulation instability in optical fibers and optical parametric amplification.

PMID- 30106942
TI  - Enhancement of the lasing efficiency of vitamin B2 in a highly polar organic
      solvent via DNA-lipid complex.
AB  - We experimentally demonstrated a green liquid laser at the wavelength of 570 nm,
      utilizing the optical gain of vitamin B2 in a highly polar organic solvent, and
      proposed an efficient method to enhance its lasing efficiency by adding DNA-lipid
      complex (DNA-CTMA) in the solution. Optical properties of vitamin B2 in the
      hexafluoro-2-propanol solvents were investigated by adding various amounts of DNA
      CTMA in terms of the UV-visible absorbance, the visible emission, and the
      fluorescence lifetime. A Fabry-Perot cavity was built to obtain the laser
      oscillation at 570 nm using a pulsed pump source at the wavelength of 450 nm, 5
      ns pulse duration, and 10 Hz repetition rate. By adding DNA-CTMA, both the output
      power and slope efficiency were enhanced along with a significant reduction of
      the lasing threshold pump power. The proposed scheme could open new potential for
      highly efficient biolasers.

PMID- 30106944
TI  - Spectroscopic characterization of Si/Mo thin-film stack at extreme ultraviolet
      range.
AB  - A noninvasive method for characterizing Si/Mo thin-film stack thickness and its
      complex transfer function using common-path optical coherence tomography is
      proposed, analyzed, and experimentally demonstrated. A laser-produced plasma
      (LPP)-based extreme ultraviolet (EUV) source was excited by a four-stage
      nanosecond Yb:fiber laser amplifier with a pulse energy of 1.01 mJ. The tabletop
      LPP EUV source was compact and stable for generating the EUV interference
      fringes. The measured complex transfer function of the Si/Mo stack was verified
      near the pristine 13.5-nm wavelength range.

PMID- 30106945
TI  - Talbot effect on orbital angular momentum beams: azimuthal intensity repetition
      rate multiplication.
AB  - We propose and experimentally demonstrate the azimuthal Talbot effect on orbital
      angular momentum (OAM) beams. By applying predetermined phases to a number of OAM
      beams carrying different topological charges, the intensity petal is self-imaged
      in the azimuthal angle, with arbitrary azimuthal repetition-rate multiplication.
      The close analogy between temporal and azimuthal Talbot self-imaging is studied.
      In addition, the effect of amplitude apodization of the OAM spectrum on the
      resulting intensity pattern, and the azimuthal Talbot effect on Laguerre-Gaussian
      beams of the same radial indices, are experimentally investigated. All of our
      experimental images are in excellent agreement with simulation results.

PMID- 30106946
TI  - Direct measurement of the composite Goos-Hanchen shift of an optical beam.
AB  - We experimentally study the Goos-Hanchen shift of a focused Gaussian optical beam
      in the critical region of incidence. We directly measure the beam's shift
      evaluated from the displacement of the location of the beam's intensity peak and
      its centroid by a novel image analysis method. We verify that the evaluation
      method has a dramatic impact on the physics of beam shift phenomena. The
      influence of wavelength, beam waist, and propagation distance on the beam shift
      is studied. Our experimental results confirm recent theoretical predictions about
      the composite Goos-Hanchen shift, including the observation of negative shifts of
      the beam's intensity peak.

PMID- 30106947
TI  - Magneto-optical Faraday effect in dysprosium oxide (Dy2O3) based ceramics
      obtained by vacuum sintering.
AB  - The method of self-propagating high-temperature synthesis of submicron powders
      with subsequent vacuum sintering was used to produce a series of optical ceramics
      based on dysprosium oxide (DyxY0.95-xLa0.05)2O3, where x=0.7, 0.85, and 0.9. The
      influence of ceramics composition on optical transmission of the obtained samples
      was investigated. The studied materials had several transparency windows in the
      visible 500-730 nm, near-IR 1900-2300 nm, and mid-IR 3500-7500 nm ranges. The
      dependence of the Verdet constant on wavelength in the 400-1940 nm range was
      measured for each ceramics composition, and analytical approximations were
      obtained. When Y and La dopants were used, the Verdet constant depended linearly
      on the concentration of Dy3+ ions, and its value in the visible wavelength range
      was about twice that of the analogous value for a terbium gallium garnet crystal.
      The high transmission and relatively high Verdet constant make the produced
      materials highly promising for fabricating Faraday devices for Tm3+ and Ho3+
      lasers and for lasers emitting in the visible spectrum.

PMID- 30106948
TI  - Assessing frequency correlation through a distinguishability measurement.
AB  - The simplicity of a question, such as wondering whether or not correlations
      characterize a certain system, collides with the experimental difficulty of
      accessing such information. Here we present a low-demanding experimental approach
      that refers to the use of a metrology scheme to obtain a conservative estimate of
      the strength of frequency correlations. Our test bed is the widespread case of a
      photon pair produced per downconversion. The theoretical architecture used to put
      the correlation degree on a quantitative ground is also described.

PMID- 30106949
TI  - Imaging using hyperuniform sampling with a single-pixel camera.
AB  - Digital cameras use detector arrays with regular geometry for optical sampling.
      Though regular arrangement was demonstrated to be optimal for two-dimensional
      sampling, it causes aliasing at high frequencies exceeding its Nyquist limit.
      Here, we proposed a randomization procedure to generate 2D hyperuniform patterns
      that can be used to suppress aliasing in image retrieval. Experiments are
      performed using a single-pixel camera, where the sampling patterns do not
      necessarily follow a fixed Cartesian geometry. Results demonstrate that the
      images reconstructed by hyperuniform patterns have a lower root mean squared
      error and exhibit less moire fringes at high frequencies than the images
      reconstructed by regular square patterns do. Furthermore, the same conclusion can
      be applied to the production of conventional detector arrays, where manufacturing
      imperfection could be utilized to suppress frequency aliasing in image retrieval.

PMID- 30106950
TI  - Near field focusing by edge diffraction.
AB  - Spherical microparticles have the ability for nonresonant focusing of light in
      the near field zone, forming nanojet (NJ) beams. Arbitrary-shaped
      microstructures, with wavelength-scale dimensions, may offer similar
      functionality with lower fabrication complexity. The focusing properties are
      ruled by the edge diffraction phenomenon. The diffraction of light on the edge of
      a dielectric microstructure forms a tilted focused beam whose deviation angle
      depends on the index ratio between the structure material and host medium. The
      beam geometry and field intensity enhancement can be tuned by varying the
      curvature of the edge line. Interference of edge diffracted waves from different
      segments of the edge line creates a condensed beam in the near field zone, the
      photonic nanojet.

PMID- 30106951
TI  - Microfluidic single-particle chemical analyzer with dual-comb coherent Raman
      spectroscopy.
AB  - Label-free particle analysis is a powerful tool in chemical, pharmaceutical, and
      cosmetic industries as well as in basic sciences, but its throughput is
      significantly lower than that of fluorescence-based counterparts. Here we present
      a label-free single-particle analyzer based on broadband dual-comb coherent Raman
      scattering spectroscopy operating at a spectroscopic scan rate of 10 kHz. As a
      proof-of-concept demonstration, we perform broadband coherent anti-Stokes Raman
      scattering measurements of polystyrene microparticles flowing on an
      acoustofluidic chip at a high throughput of >1000 particles per second. This high
      throughput label-free particle analyzer has the potential for high-precision
      statistical analysis of a large number of microparticles including biological
      cells.

PMID- 30106952
TI  - Differential phase-shift-keying demodulation by coherent perfect absorption in
      silicon photonics.
AB  - We demonstrate a novel differential phase-shift-keying (DPSK) demodulator based
      on coherent perfect absorption (CPA). Our DPSK demodulator chip device, which
      incorporates a silicon ring resonator, two bus waveguide inputs, and
      monolithically integrated detectors, operates passively at a bit rate of 10 Gbps
      at telecommunication wavelengths, and fits within a mm-scale footprint. Critical
      coupling is used to achieve efficient CPA by tuning the gap between the ring and
      bus waveguides. The device has a vertical eye opening of 12.47 mV and a quality
      factor exceeding 3*104. The fundamental principle behind this photonic circuit
      can be extended to other formats of integrated demodulators.

PMID- 30106953
TI  - Interplay of multiple pathways and activity-dependent rules in STDP.
AB  - Hebbian plasticity describes a basic mechanism for synaptic plasticity whereby
      synaptic weights evolve depending on the relative timing of paired activity of
      the pre- and postsynaptic neurons. Spike-timing-dependent plasticity (STDP)
      constitutes a central experimental and theoretical synaptic Hebbian learning
      rule. Various mechanisms, mostly calcium-based, account for the induction and
      maintenance of STDP. Classically STDP is assumed to gradually emerge in a
      monotonic way as the number of pairings increases. However, non-monotonic STDP
      accounting for fast associative learning led us to challenge this monotonicity
      hypothesis and explore how the existence of multiple plasticity pathways affects
      the dynamical establishment of plasticity. To account for distinct forms of STDP
      emerging from increasing numbers of pairings and the variety of signaling
      pathways involved, we developed a general class of simple mathematical models of
      plasticity based on calcium transients and accommodating various calcium-based
      plasticity mechanisms. These mechanisms can either compete or cooperate for the
      establishment of long-term potentiation (LTP) and depression (LTD), that emerge
      depending on past calcium activity. Our model reproduces accurately the striatal
      STDP that involves endocannabinoid and NMDAR signaling pathways. Moreover, we
      predict how stimulus frequency alters plasticity, and how triplet rules are
      affected by the number of pairings. We further investigate the general model with
      an arbitrary number of pathways and show that depending on those pathways and
      their properties, a variety of plasticities may emerge upon variation of the
      number and/or the frequency of pairings, even when the outcome after large
      numbers of pairings is identical. These findings, built upon a biologically
      realistic example and generalized to other applications, argue that in order to
      fully describe synaptic plasticity it is not sufficient to record STDP curves at
      fixed pairing numbers and frequencies. In fact, considering the whole spectrum of
      activity-dependent parameters could have a great impact on the description of
      plasticity, and a better understanding of the engram.

PMID- 30106954
TI  - Neuroinflammation and ER-stress are key mechanisms of acute bilirubin toxicity
      and hearing loss in a mouse model.
AB  - Hyperbilirubinemia (jaundice) is caused by raised levels of unconjugated
      bilirubin in the blood. When severe, susceptible brain regions including the
      cerebellum and auditory brainstem are damaged causing neurological sequelae such
      as ataxia, hearing loss and kernicterus. The mechanism(s) by which bilirubin
      exerts its toxic effect have not been completely understood to date. In this
      study we investigated the acute mechanisms by which bilirubin causes the
      neurotoxicity that contributes to hearing loss. We developed a novel mouse model
      that exhibits the neurological features seen in human Bilirubin-Induced
      Neurological Dysfunction (BIND) syndrome that we assessed with a behavioural
      score and auditory brainstem responses (ABR). Guided by initial experiments
      applying bilirubin to cultured cells in vitro, we performed whole genome gene
      expression measurements on mouse brain tissue (cerebellum and auditory brainstem)
      following bilirubin exposure to gain mechanistic insights into biochemical
      processes affected, and investigated further using immunoblotting. We then
      compared the gene changes induced by bilirubin to bacterial lipopolysaccharide
      (LPS), a well characterized inducer of neuroinflammation, to assess the degree of
      similarity between them. Finally, we examined the extent to which genetic
      perturbation of inflammation and both known and novel anti-inflammatory drugs
      could protect hearing from bilirubin-induced toxicity. The in vitro results
      indicated that bilirubin induces changes in gene expression consistent with
      endoplasmic reticulum (ER) stress and activation of the unfolded protein response
      (UPR). These gene changes were similar to the gene expression signature of
      thapsigargin-a known ER stress inducer. It also induced gene expression changes
      associated with inflammation and NF-kappaB activation. The in vivo model showed
      behavioural impairment and a raised auditory threshold. Whole genome gene
      expression analysis confirmed inflammation as a key mechanism of bilirubin
      neurotoxicity in the auditory pathway and shared gene expression hallmarks
      induced by exposure to bacterial lipopolysaccharide (LPS) a well-characterized
      inducer of neuroinflammation. Interestingly, bilirubin caused more severe damage
      to the auditory system than LPS in this model, but consistent with our hypothesis
      of neuroinflammation being a primary part of bilirubin toxicity, the hearing loss
      was protected by perturbing the inflammatory response. This was carried out
      genetically using lipocalin-2 (LCN2)-null mice, which is an inflammatory cytokine
      highly upregulated in response to bilirubin. Finally, we tested known and novel
      anti-inflammatory compounds (interfering with NF-kappaB and TNFalpha signalling),
      and also demonstrated protection of the auditory system from bilirubin toxicity.
      We have developed a novel, reversible, model for jaundice that shows movement
      impairment and auditory loss consistent with human symptoms. We used this model
      to establish ER-stress and inflammation as major contributors to bilirubin
      toxicity. Because of the rapid and reversible onset of toxicity in this novel
      model it represents a system to screen therapeutic compounds. We have
      demonstrated this by targeting inflammation genetically and with anti
      inflammatory small molecules that offered protection against bilirubin toxicity.
      This also suggests that anti-inflammatory drugs could be of therapeutic use in
      hyperbilirubinemia.

PMID- 30106955
TI  - Anticoagulation Knowledge Tool (AKT): Further evidence of validity in the Italian
      population.
AB  - INTRODUCTION: Oral Anticoagulation therapy (OAC) is highly effective in the
      management of thromboembolic disorders. An adequate level of knowledge is
      important for self-management and optimizing clinical outcomes. The
      Anticoagulation Knowledge Tool (AKT) was developed to assess OAC knowledge and
      caters for both patients prescribed direct oral anticoagulants or vitamin K
      antagonist (VKA). However, evidence regarding its psychometric proprieties,
      validity and reliability are unavailable in non-English speaking settings. For
      this reason, the aim of this study is to provide further evidence of validity for
      AKT and also developing an Italian AKT version (I-AKT) supported by evidence of
      validity and reliability. METHODS: A multiphase study was conducted which
      included the following: cultural and linguistic validity; i.e. content validity;
      construct validity; reliability assessment. The Construct validity was performed
      using the contrasted group approach using three groups comprised of health care
      providers, patients and the general public. Furthermore, Exploratory Structural
      Equation Modelling (ESEM) was performed to confirm the mono-dimensional structure
      of the items in the AKT. RESULTS: In construct validity phase 334 participants
      were enrolled. One-way ANOVA and post hoc analysis test demonstrated significant
      differences between the means knowledge scores of the three groups: 30.42+/-3.04
      vs 23.45+/- 4.57 vs14.32+/-6.07 (Statistic F = 266.83; p < .001). ESEM analysis
      demonstrates the I-AKT mono-dimensionally structure with an explained variance of
      56.42%. The scale also showed both good internal consistency reliability
      (Cronbach's alpha = 0.896) and test-retest reliability (r = 0.855). CONCLUSION:
      This study developed and validated I-AKT with supporting evidence for validity
      and reliability. The study also confirms the mono-dimensional of the items in the
      AKT. This suggest that the instrument can be useful in non-English setting for
      knowledge assessment and in potentially developing patient education materials.

PMID- 30106956
TI  - Mass azithromycin distribution for hyperendemic trachoma following a cluster
      randomized trial: A continuation study of randomly reassigned subclusters (TANA
      II).
AB  - BACKGROUND: The World Health Organization recommends annual mass azithromycin
      administration in communities with at least 10% prevalence of trachomatous
      inflammation-follicular (TF) in children, with further treatment depending on
      reassessment after 3-5 years. However, the effect of stopping mass azithromycin
      distribution after multiple rounds of treatment is not well understood. Here, we
      report the results of a cluster-randomized trial where communities that had
      received 4 years of treatments were then randomized to continuation or
      discontinuation of treatment. METHODS AND FINDINGS: In all, 48 communities with
      3,938 children aged 0-9 years at baseline in northern Ethiopia had received 4
      years of annual or twice yearly mass azithromycin distribution as part of the
      TANA I trial. We randomized these communities to either continuation or
      discontinuation of treatment. Individuals in the communities in the continuation
      arm were offered either annual or twice yearly distribution of a single directly
      observed dose of oral azithromycin. The primary outcome was community prevalence
      of ocular chlamydial infection in a random sample of children aged 0-9 years, 36
      months after baseline. We also assessed the change from baseline to 36 months in
      ocular chlamydia prevalence within each arm. We compared 36-month ocular
      chlamydia prevalence in communities randomized to continuation versus
      discontinuation in a model adjusting for baseline ocular chlamydia prevalence. A
      secondary prespecified analysis assessed the rate of change over time in ocular
      chlamydia prevalence between arms. In the continuation arm, mean antibiotic
      coverage was greater than 90% at all time points. In the discontinuation arm, the
      mean prevalence of infection in children aged 0-9 years increased from 8.3% (95%
      CI 4.2% to 12.4%) at 0 months to 14.7% (95% CI 8.7% to 20.8%, P = 0.04) at 36
      months. Ocular chlamydia prevalence in communities where mass azithromycin
      distribution was continued was 7.2% (95% CI 3.3% to 11.0%) at baseline and 6.6%
      (95% CI 1.1% to 12.0%, P = 0.64) at 36 months. The 36-month prevalence of ocular
      chlamydia was significantly lower in communities continuing treatment compared
      with those discontinuing treatment (P = 0.03). Limitations of the study include
      uncertain generalizability outside of trachoma hyperendemic regions. CONCLUSIONS:
      In this study, ocular chlamydia infection rebounded after 4 years of periodic
      mass azithromycin distribution. Continued distributions did not completely
      eliminate infection in all communities or meet WHO control goals, although they
      did prevent resurgence. TRIAL REGISTRATION: This study was prospectively
      registered at clinicaltrials.gov (clinicaltrials.gov NCT01202331).

PMID- 30106957
TI  - Circadian modulation of light-evoked avoidance/attraction behavior in Drosophila.
AB  - Many insects show strong behavioral responses to short wavelength light.
      Drosophila melanogaster exhibit Cryptochrome- and Hyperkinetic-dependent blue and
      ultraviolet (UV) light avoidance responses that vary by time-of-day, suggesting
      that these key sensory behaviors are circadian regulated. Here we show mutant
      flies lacking core clock genes exhibit defects in both time-of-day responses and
      valence of UV light avoidance/attraction behavior. Non-genetic environmental
      disruption of the circadian clock by constant UV light exposure leads to complete
      loss of rhythmic UV light avoidance/attraction behavior. Flies with ablated or
      electrically silenced circadian lateral ventral neurons have attenuated avoidance
      response to UV light. We conclude that circadian clock proteins and the circadian
      lateral ventral neurons regulate both the timing and the valence of UV light
      avoidance/attraction. These results provide mechanistic support for Pittendrigh's
      "escape from light" hypothesis regarding the co-evolution of phototransduction
      and circadian systems.

PMID- 30106958
TI  - Arboreal crops on the medieval Silk Road: Archaeobotanical studies at Tashbulak.
AB  - During the first millennium A.D., Central Asia was marked by broad networks of
      exchange and interaction, what many historians collectively refer to as the "Silk
      Road". Much of this contact relied on high-elevation mountain valleys, often
      linking towns and caravanserais through alpine territories. This cultural
      exchange is thought to have reached a peak in the late first millennium A.D., and
      these exchange networks fostered the spread of domesticated plants and animals
      across Eurasia. However, few systematic studies have investigated the cultivated
      plants that spread along the trans-Eurasian exchange during this time. New
      archaeobotanical data from the archaeological site of Tashbulak (800-1100 A.D.)
      in the mountains of Uzbekistan is shedding some light on what crops were being
      grown and consumed in Central Asia during the medieval period. The
      archaeobotanical assemblage contains grains and legumes, as well as a wide
      variety of fruits and nuts, which were likely cultivated at lower elevations and
      transported to the site. In addition, a number of arboreal fruits may have been
      collected from the wild or represent cultivated version of species that once grew
      in the wild shrubby forests of the foothills of southern Central Asia in
      prehistory. This study examines the spread of crops, notably arboreal crops,
      across Eurasia and ties together several data sets in order to add to discussions
      of what plant cultivation looked like in the central region of the Silk Road.

PMID- 30106960
TI  - A pipeline for metabarcoding and diet analysis from fecal samples developed for a
      small semi-aquatic mammal.
AB  - Metabarcoding allows the genetic analysis of pooled samples of various sources.
      It is becoming popular in the study of animal diet, especially because it allows
      the analysis of the composition of feces without the need of handling animals. In
      this work, we studied the diet of the Pyrenean desman (Galemys pyrenaicus), a
      small semi-aquatic mammal endemic to the Iberian Peninsula and the Pyrenees, by
      sequencing COI minibarcodes from feces using next-generation sequencing
      techniques. For the identification of assembled sequences, we employed a tree
      based identification method that used a reference tree of sequences of freshwater
      organisms. The comparison of freshly collected fecal samples and older samples
      showed that fresh samples produced significantly more sequencing reads. They also
      rendered more operational taxonomical units (OTUs), but not significantly. Our
      analyses of 41 samples identified 224 OTUs corresponding to species of the
      reference tree. Ephemeroptera, Diptera excl. Chironomidae, and Chironomidae were
      the most highly represented groups in terms of reads as well as samples. Other
      groups of freshwater organisms detected were Plecoptera, Trichoptera,
      Neuropteroida, Coleoptera, Crustacea, and Annelida. Our results are largely in
      line with previous morphological and genetic studies on the diet of the Pyrenean
      desman, but allowed the identification of a higher diversity of OTUs in each
      sample. Additionally, the bioinformatic pipeline we developed for deep sequencing
      of fecal samples will enable the quantitative analysis of the diet of this and
      other species, which can be highly useful to determine their ecological
      requirements.

PMID- 30106961
TI  - Adapting the Quality Maternal and Newborn Care (QMNC) Framework to evaluate
      models of antenatal care: A pilot study.
AB  - BACKGROUND: Recent evidence indicates that continuity models of maternity care
      result in improved clinical and psychosocial outcomes, but their causal
      mechanisms are poorly understood. The recent Lancet Series on Midwifery's Quality
      Maternal and Newborn Care Framework describes five components of quality care and
      their associated characteristics. As an initial step in developing this Framework
      into an evaluation toolkit, we transformed its components and characteristics
      into a topic guide to assess stakeholder perceptions and experiences of care
      provided and received. The main purpose of this study was to assess the
      feasibility of this process. METHODS: We conducted twelve focus groups in two
      Scottish health board areas with 13 pregnant women, 18 new mothers, 26 midwives
      and 12 obstetricians who had experience of a range of different models of
      maternity care. Transcripts were analysed using a six-phase approach of thematic
      analysis. We mapped the identified themes and sub-themes back to the Framework.
      RESULTS: The emerging themes and sub-themes demonstrated the feasibility of using
      the QMNC framework as a data collection tool, and as a lens for analysing the
      data. Of the four emerging themes, only Organisation Culture / Work Structure'
      mapped directly to a single Framework component. The others-'Relationships';
      'Information and support'; and 'Uncertainty'-mapped to between two and five
      components, illustrating the interconnectedness of the Framework's components.
      Some negative sub-themes mirrored positive Framework characteristics of care.
      Some re-phrasing and re-ordering of the topic guides in later focus groups
      ensured we could cover all aspects of the Framework adequately. CONCLUSION:
      Adapting the Quality Maternal and Newborn Care Framework enabled us to focus on
      aspects of care which worked well and which didn't work well for these key
      stakeholders. Identifying 'what works for whom and why' in different models of
      care is a necessary step in reinforcing and replicating the most effective models
      of care.

PMID- 30106959
TI  - Pigmentation phototype and prostate and breast cancer in a select Spanish
      population-A Mendelian randomization analysis in the MCC-Spain study.
AB  - INTRODUCTION: Phototype has been associated with an increased risk of prostate
      cancer, and it is yet unknown if it is related to other hormone-dependent
      cancers, such as breast cancer or whether this association could be considered
      causal. METHODS: We examined the association between the phototype and breast and
      prostate cancers using a Mendelian randomization analysis. We studied 1,738
      incident cases of breast cancer and another 817 cases of prostate cancer. To
      perform a Mendelian randomization analysis on the phototype-cancer relationship,
      a genetic pigmentation score was required that met the following criteria: (1)
      the genetic pigmentation score was associated with phototype in controls; (2) the
      genetic pigmentation score was not associated with confounders in the
      relationship between phototype and cancer, and (3) the genetic pigmentation score
      was associated with cancer only through its association with phototype. Once this
      genetic score is available, the association between genetic pigmentation score
      and cancer can be identified as the association between phototype and cancer.
      RESULTS: The association between the genetic pigmentation score and phototype in
      controls showed that a higher genetic pigmentation score was associated with fair
      skin, blond hair, blue eyes and the presence of freckles. Applying the Mendelian
      randomization analysis, we verified that there was no association between the
      genetic pigmentation score and cancers of the breast and prostate. CONCLUSIONS:
      Phototype is not associated with breast or prostate cancer.

PMID- 30106963
TI  - Dexmedetomidine in combination with morphine improves postoperative analgesia and
      sleep quality in elderly patients after open abdominal surgery: A pilot
      randomized control trial.
AB  - BACKGROUND: Dexmedetomidine in combination with opioids has been used for
      postoperative analgesia. The purpose of this study was to investigate the impacts
      of dexmedetomidine supplemented intravenous analgesia on morphine consumption and
      subjective sleep quality in elderly patients after open abdominal surgery.
      METHODS: This was a pilot randomized controlled trial. 58 elderly patients (age
      >= 60 years) who underwent open abdominal surgery were randomized to receive
      either dexmedetomidine supplemented morphine analgesia (0.5 mg/ml morphine plus 2
      MUg/ml dexmedetomidine in 100 ml normal saline, DEX group) or morphine analgesia
      (0.5 mg/ml morphine in 100 ml normal saline, CTRL group) for 72 hours after
      surgery. Patient-controlled analgesia pump was programmed to deliver a 2ml bolus
      with a lockout interval of 8 minutes and a background infusion at a rate of 1
      ml/h. The primary endpoint was 72-hour morphine consumption. Secondary endpoints
      included pain intensity, subjective sleep quality, and 30-day complications and
      mortality after surgery. RESULTS: The 72-hour morphine consumption was lower in
      the DEX group than in the CTRL group (median 39.0 mg [interquartile range 37.3,
      41.0] in the DEX group vs. 49.0 mg [45.5, 50.0] in the CTRL group; median
      difference -9.0 mg [95% CI -10.0, -6.0], P < 0.001). The intensity of pain within
      48 hours was lower (P<0.001 at 4, 12 and 48 hours, P = 0.007 at 24 hours) whereas
      the subjective quality of sleep was higher (P = 0.031 during the night of surgery
      and P<0.001 during the 1st night after surgery, respectively) in the DEX group
      than in the CTRL group. The incidence of 30-day complications did not differ
      significantly between groups, but it was slightly lower in the DEX group (P =
      0.060). There were no significant differences between groups regarding 30-day
      mortality and the incidences of adverse events. CONCLUSIONS: For elderly patients
      after open abdominal surgery, dexmedetomidine supplemented analgesia decreases
      morphine consumption, improves analgesic effects and subjective sleep quality
      without increasing adverse events. TRIAL REGISTRATION: Chinese Clinical Trial
      Registry ChiCTR-IPR-14005620.

PMID- 30106962
TI  - Genetic heterogeneity and mutational signature in Chinese Epstein-Barr virus
      positive diffuse large B-cell lymphoma.
AB  - Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (EBV+ DLBCL) is
      typically an aggressive tumor in elderly patients. However, in a subset of young
      patients, EBV+ DLBCL follows a relatively indolent clinical course and exhibits a
      good response to chemotherapy. This lymphoma comprises polymorphous lymphoma and
      large cell lymphomas subtypes, with the latter subtype showing a significantly
      poorer prognosis. It is unknown whether the genetic background differs between
      age groups and histopathological subtypes. To investigate the genetic basis,
      heterogeneity, and recurrently mutated genes in EBV+ DLBCL, we performed whole
      exome sequencing of DNA from 11 tissue samples of this lymphoma. Sequencing
      revealed that the most common substitution was the transition C>T/G>A. Genetic
      features-including the numbers of mutated genes in exonic region, single
      nucleotide variants (SNV), and indels-did not significantly differ between age
      groups or histological subtypes. Matching with the COSMIC database revealed that
      the main mutational signature was signature 3, which is associated with failure
      of DNA double-strand break-repair by homologous recombination. Mutant-Allele
      Tumor Heterogeneity (MATH) scores showed that EBV+ DLBCL exhibited broad
      intratumor heterogeneity, and were positively correlated with Ann Arbor Stage and
      >=2 extranodal lesion sites. We identified 57 selected recurrently mutated genes.
      The most commonly mutated five genes-LNP1 (11/11), PRSS3 (10/11), MUC3A (9/11),
      FADS6 (9/11), and TRAK1 (8/11)-were validated by Sanger sequencing. These mutated
      genes have not previously been identified. Overall, our present results
      demonstrate the tremendous genetic heterogeneity underlying EBV+ DLBCLs, and
      highlight the need for personalized therapeutic approaches to treating these
      patients.

PMID- 30106964
TI  - Administration of intravenous antibiotics in patients with open fractures is
      dependent on emergency room triaging.
AB  - BACKGROUND: Recent literature has demonstrated that emergent administration of
      antibiotics is perhaps more critical than even emergent debridement. Most recent
      studies recommend patients receive antibiotics no later than 1 hour after injury
      to prevent infection. The objective of this study is to evaluate the time to
      antibiotic administration after patients with open fractures arrive to a trauma
      center depending on triaging team. METHODS: A retrospective study at a level 1
      Trauma center from January 2013 to March 2015 where 117 patients with open
      fractures were evaluated. Patients who presented with open fractures of the
      extremities or pelvis were considered. Subjects were identified using Current
      Procedural Terminology (CPT) codes. Patients aged 18 and older were analyzed for
      Gustilo type, antibiotics administered in the emergency room (ER), presence of an
      antibiotic allergy, post-operative antibiotic regimen and number of debridements,
      among others. Additionally, whether a patient was triaged by ER doctors or trauma
      surgeons (and made a trauma activation) was evaluated. Outcome measurements
      included time to intravenous (IV) antibiotic administration and time to surgical
      debridement. RESULTS: Patients received IV cefazolin a median of 17 minutes after
      arrival. Eighty-five patients who were made trauma activations received cefazolin
      14 minutes after arrival while 24 non-trauma patients received cefazolin 53
      minutes after arrival (p = <0.0001). The median time to gentamicin administration
      for all patients was 180 minutes. Patients not upgraded to a trauma received
      gentamicin 263 minutes after arrival, while patients upgraded received gentamicin
      176 minutes after arrival. There was no statistically significant difference
      between the timing to cefazolin or gentamicin based on Gustilo type. CONCLUSIONS:
      Overall, patients that arrive at our institution with open fractures receive IV
      cefazolin significantly faster when trauma surgeons evaluate the patient.
      Additionally, delays in gentamicin administration are demonstrated in both
      triaging groups. This is due to the fact that cefazolin is stocked in the
      hospital ER, while gentamicin is commonly not due to weight-based dosing
      requirements precluding a standard dose. Improvements can be made to antibiotic
      administration of non-trauma patients and those requiring gentamicin via improved
      education and awareness of open fractures.

PMID- 30106965
TI  - Dicyandiamide has more inhibitory activities on nitrification than thiosulfate.
AB  - Dicyandiamide (DCD) and thiosulfates are two type of nitrification inhibitors
      (NIs) that have been widely used in agriculture to improve nitrogen (N)
      fertilizer use efficiency and mitigate negative effect of N on environment.
      Little information is available concerning the comparison of the efficacy of DCD
      and thiosulfate on N transformations in soil. The aim of this study was to
      compare the effects of DCD and thiosulfate (K2S2O3) on changes of NH4+-N,
      nitrification inhibition and N recovery in a latosolic red soil. An incubation
      experiment was conducted with four treatments of control (CK), N, N+DCD, and
      N+K2S2O3. Soil samples were collected periodically over 50 d to determine
      concentrations of mineral N, and the amoA gene abundance of ammonia monooxygenase
      (AMO) for ammonia-oxidizing bacteria (AOB) was estimated by qPCR after 10 d
      incubation. In the N treatment, 67.8% of the applied N as NH4+-N disappeared from
      the mineral N pool and only 2.7% and 30.8% of the applied N was accumulated as
      NO2--N and NO3--N, respectively. Addition of DCD and thiosulfate to the soil
      prevented NH4+-N disappearance by 63.0% and 13.6%, respectively. DCD suppressed
      the production of NO2--N by 97.41%, whereas thiosulfate increased accumulation of
      NO2--N by 14.6%. Application of N along with DCD and thiosulfate inhibited
      nitrification, respectively, by 72.6% and 33.1%, resulting in the delay of the
      nitrification process for 30 days and 10 days, respectively. Apparent N recovery
      in N treatment was 66.2%, which increased by 55.2% and 4.8% by DCD and
      thiosulfate, respectively. Numbers of AOB amoA gene copy was significantly
      inhibited by both DCD and thiosulfate, and the stronger inhibition induced by DCD
      than thiosulfate was recorded. Results indicated that both DCD and thiosulfate
      were effective inhibitors for NH4+-N oxidation, NO3--N production, mineral N
      losses and AOB growth. DCD showed a more pronounced effect on nitrification
      inhibition than thiosulfate.

PMID- 30106967
TI  - On the performance analysis of a DCSK system under the pulse jamming environment.
AB  - This paper considers the DCSK system under jamming environment. We consider both
      fast and slow switching pulse jamming (PJ). We derive approximations of the
      system bit error rates (BERs) in analytic expressions containing only well-known
      special functions, from which we show that for both jamming cases increasing the
      spreading factor can enhance the BER. In addition, we reveal that under the fast
      switching PJ, the BER does not depend on the jamming duty cycle rho when rho <=
      0.5, however when rho > 0.5, increasing its value degrades the BER. Moreover, we
      find out that under the slow switching PJ, increasing rho may either enhance or
      degrade the BER.

PMID- 30106966
TI  - Integration and multiplexing of positional and contextual information by the
      hippocampal network.
AB  - The hippocampus is known to store cognitive representations, or maps, that encode
      both positional and contextual information, critical for episodic memories and
      functional behavior. How path integration and contextual cues are dynamically
      combined and processed by the hippocampus to maintain these representations
      accurate over time remains unclear. To answer this question, we propose a two-way
      data analysis and modeling approach to CA3 multi-electrode recordings of a moving
      rat submitted to rapid changes of contextual (light) cues, triggering back-and
      forth instabitilies between two cognitive representations ("teleportation"
      experiment of Jezek et al). We develop a dual neural activity decoder, capable of
      independently identifying the recalled cognitive map at high temporal resolution
      (comparable to theta cycle) and the position of the rodent given a map.
      Remarkably, position can be reconstructed at any time with an accuracy comparable
      to fixed-context periods, even during highly unstable periods. These findings
      provide evidence for the capability of the hippocampal neural activity to
      maintain an accurate encoding of spatial and contextual variables, while one of
      these variables undergoes rapid changes independently of the other. To explain
      this result we introduce an attractor neural network model for the hippocampal
      activity that process inputs from external cues and the path integrator. Our
      model allows us to make predictions on the frequency of the cognitive map
      instability, its duration, and the detailed nature of the place-cell population
      activity, which are validated by a further analysis of the data. Our work
      therefore sheds light on the mechanisms by which the hippocampal network achieves
      and updates multi-dimensional neural representations from various input streams.

PMID- 30106969
TI  - Suppression of overlearning in independent component analysis used for removal of
      muscular artifacts from electroencephalographic records.
AB  - This paper addresses the overlearning problem in the independent component
      analysis (ICA) used for the removal of muscular artifacts from
      electroencephalographic (EEG) records. We note that for short EEG records with
      high number of channels the ICA fails to separate artifact-free EEG and muscular
      artifacts, which has been previously attributed to the phenomenon called
      overlearning. We address this problem by projecting an EEG record into several
      subspaces with a lower dimension, and perform the ICA on each subspace
      separately. Due to a reduced dimension of the subspaces, the overlearning is
      suppressed, and muscular artifacts are better separated. Once the muscular
      artifacts are removed, the signals in the individual subspaces are combined to
      provide an artifact free EEG record. We show that for short signals and high
      number of EEG channels our approach outperforms the currently available ICA based
      algorithms for muscular artifact removal. The proposed technique can efficiently
      suppress ICA overlearning for short signal segments of high density EEG signals.

PMID- 30106968
TI  - fMRI repetition suppression reveals no sensitivity to trait judgments from faces
      in face perception or theory-of-mind networks.
AB  - The human face cues a wealth of social information, but the neural mechanisms
      that underpin social attributions from faces are not well known. In the current
      fMRI experiment, we used repetition suppression to test the hypothesis that
      populations of neurons in face perception and theory-of-mind neural networks
      would show sensitivity to faces that cue distinct trait judgments. Although faces
      were accurately discriminated based on associated traits, our results showed no
      evidence that face or theory-of-mind networks showed repetition suppression for
      face traits. Thus, we do not provide evidence for population coding models of
      face perception that include sensitivity to high and low trait features. Due to
      aspects of the experimental design, which bolstered statistical power and
      sensitivity, we have reasonable confidence that we could detect effects of a
      moderate size, should they exist. The null findings reported here, therefore, add
      value to models of neural organisation in social perception by showing instances
      where effects are absent or small. To test the generalisability of our findings,
      future work should test different types of trait judgment and different types of
      facial stimuli, in order to further probe the neurobiological bases of impression
      formation based on facial appearance.

PMID- 30106970
TI  - Mathematical modeling of disease dynamics in SDHB- and SDHD-related
      paraganglioma: Further step in understanding hereditary tumor differences and
      future therapeutic strategies.
AB  - Succinate dehydrogenase subunit B and D (SDHB and SDHD) mutations represent the
      most frequent cause of hereditary pheochromocytoma and paraganglioma (PPGL).
      Although truncation of the succinate dehydrogenase complex is thought to be the
      disease causing mechanism in both disorders, SDHB and SDHD patients exihibit
      different phenotypes. These phenotypic differences are currently unexplained by
      molecular genetics. The aim of this study is to compare disease dynamics in these
      two conditions via a Markov chain model based on 4 clinically-defined steady
      states. Our model corroborates at the population level phenotypic observations in
      SDHB and SDHD carriers and suggests potential explanations associated with the
      probabilities of disease maintenance and regression. In SDHB-related syndrome,
      PPGL maintenance seems to be reduced compared to SDHD (p = 0.04 vs 0.95) due to
      higher probability of tumor cell regression in SDHB vs SDHD (p = 0.87 vs 0.00).
      However, when SDHB-tumors give rise to metastases, metastatic cells are able to
      thrive with decreased probability of regression compared with SDHD counterparts
      (p = 0.17 vs 0.89). By constrast, almost all SDHD patients develop PGL (mainly
      head and neck) that persist throughout their lifetime. However, compared to SDHB,
      maintenance of metastatic lesions seems to be less effective for SDHD (p = 0.83
      vs 0.11). These findings align with data suggesting that SDHD-related PPGL
      require less genetic events for tumor initiation and maintenance compared to
      those related to SDHB, but fail to initiate biology that promotes metastatic
      spread and metastatic cell survival in host tissues. By contrast, the higher
      number of genetic abnormalities required for tumor initiation and maintenance in
      SDHB PPGL result in a lower penetrance of PGL, but when cells give rise to
      metastases they are assumed to be better adapted to sustain survival. These
      proposed differences in disease progression dynamics between SDHB and SDHD
      diseases provide new cues for future exploration of SDHx PPGL behavior, offering
      considerations for future specific therapeutic and prevention strategies.

PMID- 30106971
TI  - Complexity in disease management: A linked data analysis of multimorbidity in
      Aboriginal and non-Aboriginal patients hospitalised with atherothrombotic disease
      in Western Australia.
AB  - BACKGROUND: Hospitalisation for atherothrombotic disease (ATD) is expected to
      rise in coming decades. However, increasingly, associated comorbidities impose
      challenges in managing patients and deciding appropriate secondary prevention. We
      investigated the prevalence and pattern of multimorbidity (presence of two or
      more chronic conditions) in Aboriginal and non-Aboriginal Western Australian
      residents with ATDs. METHODS AND FINDINGS: We used population-based de-identified
      linked administrative health data from 1 January 2000 to 30 June 2014 to identify
      a cohort of patients aged 25-59 years admitted to Western Australian hospitals
      with a discharge diagnosis of ATD. The prevalence of common chronic diseases in
      these patients was estimated and the patterns of comorbidities and
      multimorbidities empirically explored using two different approaches:
      identification of the most commonly occurring pairs and triplets of comorbid
      diseases, and through latent class analysis (LCA). Half of the cohort had
      multimorbidity, although this was much higher in Aboriginal people (Aboriginal:
      79.2% vs. non-Aboriginal: 39.3%). Only a quarter were without any documented
      comorbidities. Hypertension, diabetes, alcohol abuse disorders and acid peptic
      diseases were the leading comorbidities in the major comorbid combinations across
      both Aboriginal and non-Aboriginal cohorts. The LCA identified four and six
      distinct clinically meaningful classes of multimorbidity for Aboriginal and non
      Aboriginal patients, respectively. Out of the six groups in non-Aboriginal
      patients, four were similar to the groups identified in Aboriginal patients. The
      largest proportion of patients (33% in Aboriginal and 66% in non-Aboriginal) was
      assigned to the "minimally diseased" (or relatively healthy) group, with most
      patients having less than two conditions. Other groups showed variability in
      degree and pattern of multimorbidity. CONCLUSION: Multimorbidity is common in ATD
      patients and the comorbidities tend to interact and cluster together. Physicians
      need to consider these in their clinical practice. Different treatment and
      secondary prevention strategies are likely to be useful for management in these
      cluster groups.

PMID- 30106972
TI  - A large-scale application of project prioritization to threatened species
      investment by a government agency.
AB  - In a global environment of increasing species extinctions and decreasing
      availability of funds with which to combat the causes of biodiversity loss,
      maximising the efficiency of conservation efforts is crucial. The only way to
      ensure maximum return on conservation investment is to incorporate the cost,
      benefit and likelihood of success of conservation actions into decision-making in
      a systematic and objective way. Here we report on the application of a Project
      Prioritization Protocol (PPP), first implemented by the New Zealand Government,
      to target and prioritize investment in threatened species in New South Wales,
      Australia, under the state's new Saving our Species program. Detailed management
      prescriptions for 368 threatened species were developed via an expert elicitation
      process, and were then prioritized using quantitative data on benefit, likelihood
      of success and implementation cost, and a simple cost-efficiency equation. We
      discuss the outcomes that have been realized even in the early stages of the
      program; including the efficient development of planning resources made available
      to all potential threatened species investors and the demonstration of a
      transparent and objective approach to threatened species management that will
      significantly increase the probability of meeting an objective to secure the
      greatest number of threatened species from extinction.

PMID- 30106973
TI  - More is not always better: An experimental individual-level validation of the
      randomized response technique and the crosswise model.
AB  - Social desirability and the fear of sanctions can deter survey respondents from
      responding truthfully to sensitive questions. Self-reports on norm breaking
      behavior such as shoplifting, non-voting, or tax evasion may thus be subject to
      considerable misreporting. To mitigate such response bias, various indirect
      question techniques, such as the randomized response technique (RRT), have been
      proposed. We evaluate the viability of several popular variants of the RRT,
      including the recently proposed crosswise-model RRT, by comparing respondents'
      self-reports on cheating in dice games to actual cheating behavior, thereby
      distinguishing between false negatives (underreporting) and false positives
      (overreporting). The study has been implemented as an online survey on Amazon
      Mechanical Turk (N = 6, 505). Our results from two validation designs indicate
      that the forced-response RRT and the unrelated-question RRT, as implemented in
      our survey, fail to reduce the level of misreporting compared to conventional
      direct questioning. For the crosswise-model RRT we do observe a reduction of
      false negatives. At the same time, however, there is a non-ignorable increase in
      false positives; a flaw that previous evaluation studies relying on comparative
      or aggregate-level validation could not detect. Overall, none of the evaluated
      indirect techniques outperformed conventional direct questioning. Furthermore,
      our study demonstrates the importance of identifying false negatives as well as
      false positives to avoid false conclusions about the validity of indirect
      sensitive question techniques.

PMID- 30106974
TI  - Bigleaf-An R package for the calculation of physical and physiological ecosystem
      properties from eddy covariance data.
AB  - We present the R package bigleaf (version 0.6.5), an open source toolset for the
      derivation of meteorological, aerodynamic, and physiological ecosystem properties
      from eddy covariance (EC) flux observations and concurrent meteorological
      measurements. A 'big-leaf' framework, in which vegetation is represented as a
      single, uniform layer, is employed to infer bulk ecosystem characteristics top
      down from the measured fluxes. Central to the package is the calculation of a
      bulk surface/canopy conductance (Gs/Gc) and a bulk aerodynamic conductance (Ga),
      with the latter including formulations for the turbulent and canopy boundary
      layer components. The derivation of physical land surface characteristics such as
      surface roughness parameters, wind profile, aerodynamic and radiometric surface
      temperature, surface vapor pressure deficit (VPD), potential evapotranspiration
      (ET), imposed and equilibrium ET, as well as vegetation-atmosphere decoupling
      coefficients, is described. The package further provides calculation routines for
      physiological ecosytem properties (stomatal slope parameters, stomatal
      sensitivity to VPD, bulk intercellular CO2 concentration, canopy photosynthetic
      capacity), energy balance characteristics (closure, biochemical energy),
      ancillary meteorological variables (psychrometric constant, saturation vapor
      pressure, air density, etc.), customary unit interconversions and data filtering.
      The target variables can be calculated with a different degree of complexity,
      depending on the amount of available site-specific information. The utilities of
      the package are demonstrated for three single-level (above-canopy) eddy
      covariance sites representing a temperate grassland, a temperate needle-leaf
      forest, and a Mediterranean evergreen broadleaf forest. The routines are further
      tested for a two-level EC site (tree and grass layer) located in a Mediterranean
      oak savanna. The limitations and the ecophysiological interpretation of the
      derived ecosystem properties are discussed and practical guidelines are given.
      The package provides the basis for a consistent, physically sound, and
      reproducible characterization of biometeorological conditions and ecosystem
      physiology, and is applicable to EC sites across vegetation types and climatic
      conditions with minimal ancillary data requirements.

PMID- 30106976
TI  - Recommended irrigation volume for an intravenous port: Ex vivo simulation study.
AB  - BACKGROUND: An intravenous port, which differs from a central venous catheter,
      has an injection chamber at the end of the catheter. This structural difference
      causes the irrigation flow pattern to be quite different from that of the central
      venous catheter. Furthermore, the intraluminal volume differs due to the size of
      the injection chamber and implanted catheter length. Hence, the ideal recommended
      irrigation volume varies because of differences in intraluminal volume, however,
      the recommended irrigation volume is 10 ml and may be a cause for reported port
      malfunctions. This study investigates the best irrigation volume for an
      intravenous port by simulating the clinical scenario ex-vivo to access its
      usefulness. MATERIALS AND METHODS: This study was composed of two tests. The
      irrigation volume test attempted to quantify the irrigation volume of an
      implanted port while the irrigation rate test attempted to simulate daily nursing
      practice in order to clarify the effect of irrigation flow. The human blood
      needed for the simulation was donated by volunteers and the total volume was 10
      ml per test. The irrigation volume test was done by syringe pump with varying pre
      set irrigation volume after the port and connected catheter were filled with
      volunteer blood. After irrigation with pre-set volume, the retained intraluminal
      solution was collected and quantified by Bradford assay in order to titrate the
      best irrigation volume. The irrigation rate test tried to simulate daily
      maintenance practice in different settings with the quantified irrigation volume
      as identified by the irrigation volume test. The retained intraluminal solution
      was collected and quantified by Bradford assay in order to confirm the efficacy
      of the quantified irrigation volume. RESULTS: In both SVC and IVC ports, we
      identified the twenty times the intravascular volume as sufficient for a complete
      wash out of the blood component in the irrigation volume test. The minimal
      irrigation volume for SVC and IVC port were 10 ml and 15.6 ml respectively. In
      irrigation rate test, the irrigation for SVC and IVC port was 10 and 20 ml,
      respectively, for the sake of preparation convenience. We not only identified the
      importance of preparation, i.e. irrigation of the extension line but also
      confirmed the efficacy of the recommended irrigation volume. CONCLUSION: The
      irrigation volume should be varied according to the intraluminal volume.
      Maintenance should be performed after the extension line has been irrigated. The
      recommended port irrigation volume for SVC and IVC route were 10 and 20 ml,
      respectively.

PMID- 30106977
TI  - Small-scale forestry and carbon offset markets: An empirical study of Vermont
      Current Use forest landowner willingness to accept carbon credit programs.
AB  - This study investigates the preferences of small forest landowners regarding
      forest carbon credit programs while documenting characteristics of potentially
      successful frameworks. We designed hypothetical carbon credit programs with
      aggregated carbon offset projects and requirements of existing voluntary and
      compliance protocols in mind. We administered a mail survey to 992 forest
      landowners in Vermont's Current Use Program utilizing best-worst choice, a novel
      preference elicitation technique, to elicit their preferences about these
      programs. We found that small forest landowners see revenue as the most important
      factor in a carbon credit program and the duration of the program as the least
      important factor. Landowners reported that shorter program duration, higher
      revenue, and lower withdrawal penalties positively impact their willingness to
      accept forest carbon credit programs. Notably, our study includes carbon credit
      program implementer as a key program attribute, allowing us to quantify
      landowners' tradeoffs between non-profit, for-profit, and government
      organizations. Overall, we found that landowners significantly prefer working
      with a non-profit organization. Based on monetary estimates of willingness-to
      accept compensation, our results suggest that aggregated forest carbon offset
      projects incorporating small forest landowners could be piloted successfully in
      Vermont by non-profit organizations while maintaining relatively strict
      guidelines of existing carbon offset protocols.

PMID- 30106979
TI  - Correction: Body-size structure of Central Iberian mammal fauna reveals
      semidesertic conditions during the middle Miocene Global Cooling Event.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0186762.].

PMID- 30106978
TI  - Cytotoxicity of white birch bud extracts: Perspectives for therapy of tumours.
AB  - Birch buds (Gemmae Betulae) are widely used in Russian and Chinese traditional
      medicine mainly as a diuretic and diaphoretic agent but also as an antiseptic,
      anti-inflammatory and analgesic. Despite the long history of therapeutic use of
      birch buds in folk medicine, the existing information on their chemical
      composition and pharmacological effects is insufficient. This circumstance
      warrants further study of the chemistry and pharmacology of birch buds. The
      present study was designed to investigate (a) the chemical composition of buds
      from two species of white birch and (b) the in vitro cytotoxic effect of extracts
      from these sources on selected tumour cells. Extracts from Betula pubescens Ehrh.
      and Betula pendula Roth. buds were obtained using three different methods: carbon
      dioxide supercritical fluid extraction (SFE), washing of exudate covering whole
      buds, and extraction of milled buds with diethyl ether. The chemical composition
      of extracts was investigated by GC-MS. Cytotoxicity was determined by MTT assay,
      and cell proliferation was determined by [3H]thymidine uptake in cancer cells and
      normal skin fibroblasts. The GC-MS investigation identified a total of 150
      substances of different classes. The chemical composition of B. pubescens and B.
      pendula buds differed, with bud extracts from the former containing a relatively
      high quantity of sesquiterpenoids and flavonoids, while the main components of
      extracts from the latter were triterpenoids. The results of the biological assay
      indicated that birch bud extracts demonstrated time- and concentration-dependent
      and differential cytotoxicity. The highest cytotoxic activity demonstrated bud
      exudates and SFE extracts obtained from both Betula species. The rich chemical
      composition of birch buds suggests the possibility of a wider spectrum of
      biological activity than previously thought. Birch bud extracts could be a
      promising source of compounds with cytotoxic activity against various cancers.

PMID- 30106980
TI  - Optimization of total phenolic content from Terminalia chebula Retz. fruits using
      response surface methodology and evaluation of their antioxidant activities.
AB  - Ultrasonic-assisted extraction (UAE), using aqueous ethanol as the solvent, was
      firstly applied to extract phenolic compounds from Terminalia chebula Retz.
      fruits (T. chebula fruits). In this study, ethanol concentration (%), ultrasonic
      intensity (W/cm2), particle diameter (mm), extraction temperature ( degrees C),
      ultrasonic time (min), liquid-solid ratio (mL/g) and extraction cycle were
      investigated by single-factor experiment and then optimized using a Box-Behnken
      design. The optimized result for UAE was 68% ethanol concentration, ultrasonic
      intensity of 3.6 W/cm2, solid-liquid ratio of 23 mg/mL, particle size of 0.18 mm
      and ultrasonic time of 20 min for 2 times at 70  degrees C. The yield of total
      phenolic was 448.7 +/- 2.15 mg GAE/g DW under the above optimum conditions, which
      agreed with the predicted value (447.8 mg GAE/g DW). Compared to conventional
      solvent extraction (CSE), UAE extracts showed excellent DPPH radical, DPPH, ABTS
      scavenging activities and reducing power in a dose-dependent manner, and better
      than that of CSE extracts. Additionally, the extract of the T. chebula fruits was
      analyzed by HPLC-ESI/MS. In summary, UAE could effectively extract phenolic
      compounds from T. chebula fruits. In addition, the extract could be used as a
      potential source of natural antioxidants.

PMID- 30106975
TI  - Toward the 2020 goal of soil-transmitted helminthiasis control and elimination.

PMID- 30106981
TI  - FGF21 increases water intake, urine output and blood pressure in rats.
AB  - Fibroblast growth factor 21 (FGF21) is a hormone secreted by the liver in
      response to metabolic stress. In addition to its well-characterized effects on
      energy homeostasis, FGF21 has been shown to increase water intake in animals. In
      this study, we sought to further explore the effects of FGF21 on fluid
      homeostasis in rats. A single dose of a long-acting FGF21 analog, PF-05231023,
      significantly increased water consumption, which was accompanied by an elevation
      in urine output that appeared prior to a significant change in water intake. We
      observed that FGF21 rapidly and significantly increased heart rate and blood
      pressure in telemeter-implanted rats, before changes in urine output and water
      intake were observed. Our data suggest that sympathetic activation may contribute
      to the pathogenesis by which FGF21 increases blood pressure as the baroreceptor
      unloading induced reflex tachycardia was significantly elevated in FGF21-treated
      animals. However, FGF21 was still capable of causing hypertension in animals in
      which approximately 40% of the sympathetic post-ganglionic neurons were ablated.
      Our data suggest that FGF21-induced water intake is in fact secondary to
      diuresis, which we propose to be a compensatory mechanism engaged to alleviate
      the acute hypertension caused by FGF21.

PMID- 30106983
TI  - Qualitative and quantitative analysis of chemicals emitted from the pheromone
      gland of individual Heliothis subflexa females.
AB  - The chemicals emitted from the sex pheromone gland of individual Heliothis
      subflexa females were sampled using a short section of thick-film megabore fused
      silica capillary column, and the pheromone glands of the same females were
      extracted after the effluvia collection. Both samples were treated with a
      silylation reagent, and then subjected to gas chromatography-chemical ionization
      mass spectrometry for quantitative and qualitative analysis of all components.
      The total amount of all 11 components emitted from the glands of calling females
      was 153 ng/female/hr, which was substantially higher than previously reported.
      The ratios of the pheromone components in the volatile emissions and pheromone
      gland extracts were generally similar to previous studies, but with notable
      differences. The collections of volatiles and gland extractions contained,
      respectively: Z9-14:Ald (1.57%, 1.35%), 14:Ald (3.78%, 1.51%), Z7 + Z9-16:Ald
      (9.60%, 3.59%), Z11-16:Ald (76.14%, 18.94%), 16:Ald (2.95%, 2.17%), Z9-16:OH
      (0.07%, 7.21%), Z11-16:OH (1.11%, 49.04%), Z7-16:OAc (0.48%, 1.73%), Z9-16:OAc
      (1.32%, 4.02%), and Z11-16:OAc (2.98%, 10.43%). The thick-film megabore column is
      an efficient approach for sampling the headspace for semiochemicals.

PMID- 30106982
TI  - Modifiable factors associated with bone health in Malaysian adolescents utilising
      calcaneus quantitative ultrasound.
AB  - Maximizing bone mineral accrual to attain an optimal peak bone mass (PBM),
      particularly during adolescence, appears to be an effective protective strategy
      in the prevention of osteoporosis. This study aimed to evaluate the influence of
      physical activity (PA), fat mass (FM), lean mass (LM), body mass index (BMI),
      calcium, or combination of vitamin D supplement intake, smoking and alcohol
      drinking status on bone health assessed by calcaneus quantitative ultrasound
      (QUS) in a healthy adolescent population. The participants comprised of 920 male
      and female secondary school adolescents aged 15-17 years old. Quantitative
      ultrasound measurements of the left heel were performed using Lunar Achilles EX
      II, which included results of broadband ultrasound attenuation (BUA), speed of
      sound (SOS), and a calculated stiffness index (SI). Multivariable linear
      regression analyses revealed that-PA was positively associated with all three QUS
      indices in both genders; BMI was positively associated with SI and SOS in
      females; LM was positively associated with BUA in both genders; and FM was
      negatively associated with SI in females. These variables accounted for 32.1%,
      21.2% and 29.4% of females' SOS, BUA and SI variances (p<0.001), respectively and
      23.6%, 15.4% and 17.2% of males' SOS, BUA and SI variances (p<0.001),
      respectively. Promoting health benefits from physical activity could influence
      bone status and consequently improve PBM, which is a potent protective
      determinant against osteoporosis in adulthood.

PMID- 30106984
TI  - Age- and sex-dependent changes in sympathetic activity of the left ventricular
      apex assessed by 18F-DOPA PET imaging.
AB  - BACKGROUND: Sexual dimorphism in cardiac sympathetic outflow has recently gained
      attention in the context of Takotsubo cardiomyopathy. Previous studies suggest
      that there are sex- and age-dependent differences in peripheral autonomic
      control, however, data on cardiac-specific sympathetic activation in aged women
      and men are lacking. METHODS AND RESULTS: Regional quantitative analysis of
      cardiac fluorine-18 (18F)- Dihydroxyphenylalanine (DOPA) uptake was
      retrospectively performed in 133 patients (69 females, mean age 52.4+/-17.7
      years) referred for assessment of neuroendocrine tumours (NET) by Positron
      Emission-Tomography. Cardiac 18F-DOPA uptake was significantly higher in women as
      compared to men (1.33+/-0.21 vs. 1.18+/-0.24, p<0.001). This sex-difference was
      most pronounced in the apical region of the left ventricle (LV, 1.30+/-0.24 in
      women vs. 1.13+/-0.25 in men, p<0.001) and in individuals >55 years of age
      (1.39+/-0.25 in women vs. 1.09+/-0.24 in men, p<0.001). Women showed a prominent
      increase in myocardial 18F-DOPA uptake with age with the strongest increase seen
      in the LV apical region (r = 0.34, p = 0.004). Accordingly, sex and age were
      selected as significant predictors of LV apical 18F-DOPA uptake in a stepwise
      linear regression model. No age-dependent changes of cardiac 18F-DOPA uptake were
      observed in men or in the right ventricular region. CONCLUSION: Our study
      suggests that aging is related to sex-specific changes in regional cardiac
      sympathetic activity. Future studies will have to assess whether the increase in
      LV apical 18F-DOPA uptake with age in women is of pathogenic relevance for the
      higher susceptibility of postmenopausal women to conditions associated with
      increased sympathetic activity.

PMID- 30106985
TI  - Noninvasive scoring systems predict hepatic and extra-hepatic cancers in patients
      with nonalcoholic fatty liver disease.
AB  - BACKGROUND: Liver fibrosis predicts liver-related morbidity and mortality in
      patients with non-alcoholic fatty liver disease (NAFLD). Non-invasive scores
      correlate with the degree of liver fibrosis in these patients. AIMS AND METHODS:
      To investigate the accuracy of noninvasive scoring systems in predicting long
      term outcomes and cancer incidence of patients with NAFLD, we performed a single
      center retrospective study of patients with biopsy proven NAFLD. Mean follow up
      period was 100 months. Outcomes included liver-related complications,
      hospitalizations, overall mortality and the development of any malignancies.
      RESULTS: 32 patients had advanced fibrosis (F3-F4) per biopsy at baseline and 121
      patients had mild to moderate fibrosis (F0-F2). Both advanced histologic fibrosis
      stage as well as higher non-invasive scores predicted repeated hospitalizations
      and longer hospitalization stays. In a multivariate analysis, liver fibrosis (p =
      0.002), FIB-4 score (p<0.001), NFS (p<0.001) but not APRI score (p = 0.07) were
      predictors of overall mortality, and the occurrence of malignancies was
      associated with higher APRI (p<0.001), FIB-4 (p<0.001) and NFS (p = 0.008)
      scores, but not with advanced fibrosis, as determined by liver biopsy (p =
      0.105). CONCLUSIONS: In NAFLD patients, noninvasive scoring systems are good
      predictors of morbidity and mortality and may have an additive value in
      predicting the development of hepatic and extra-hepatic cancers.

PMID- 30106986
TI  - Boysenberry polyphenol inhibits endothelial dysfunction and improves vascular
      health.
AB  - Endothelial cells have an important role in maintaining vascular homeostasis. Age
      related disorders (including obesity, diabetes, and hypertension) or aging per se
      induce endothelial dysfunction that predisposes to the development of
      atherosclerosis. Polyphenols have been reported to suppress age-related
      endothelial cell disorders, but their role in vascular function is yet to be
      determined. We investigated the influence of boysenberry polyphenol on vascular
      health under metabolic stress in a murine model of dietary obesity. We found that
      administration of boysenberry polyphenol suppressed production of reactive oxygen
      species (ROS) and increased production of nitric oxide (NO) in the aorta. It has
      been reported that p53 induces cellular senescence and has a crucial role in age
      related disorders, including heart failure and diabetes. Administration of
      boysenberry polyphenol significantly reduced the endothelial p53 level in the
      aorta and ameliorated endothelial cell dysfunction in iliac arteries under
      metabolic stress. Boysenberry polyphenol also reduced ROS and p53 levels in
      cultured human umbilical vein endothelial cells (HUVECs), while increasing NO
      production. Uncoupled endothelial nitric oxide synthase (eNOS monomer) is known
      to promote ROS production. We found that boysenberry polyphenol reduced eNOS
      monomer levels both in vivo and in vitro, along with an increase of eNOS
      dimerization. To investigate the components of boysenberry polyphenol mediating
      these favorable biological effects, we extracted the anthocyanin fractions. We
      found that anthocyanins contributed to suppression of ROS and p53, in association
      with increased NO production and eNOS dimerization. In an ex vivo study,
      anthocyanins promoted relaxation of iliac arteries from mice with dietary
      obesity. These findings indicate that boysenberry polyphenol and anthocyanins, a
      major component of this polyphenol, inhibit endothelial dysfunction and
      contribute to maintenance of vascular homeostasis.

PMID- 30106987
TI  - Post-hospital mortality in children aged 2-12 years in Tanzania: A prospective
      cohort study.
AB  - BACKGROUND: Sub-Saharan Africa has the highest rates of child mortality
      worldwide. Little is known about post-hospital outcomes after an index
      hospitalization for older children. We determined 12-month post-hospital
      mortality rate and identified factors associated with higher mortality. METHODS:
      In this prospective cohort study, we enrolled children 2-12 years of age admitted
      to the pediatric wards of two public hospitals in northwestern Tanzania.
      Participants or proxies were contacted at 3, 6 and 12 months post
      hospitalization. The primary outcome measured was mortality. Factors associated
      with mortality were determined using Cox regression analysis. RESULTS: A total of
      506 participants were enrolled. In-hospital mortality rate was 7.7% (39/506). Of
      the 467 participants discharged, the post-hospital mortality rate was 10.1%
      (47/467). Sickle cell disease (Hazard Ratio (HR) 3.32, 95% CI 1.44-7.68), severe
      malnutrition (HR 3.19, 95% CI 1.18-8.57), neurologic diseases (HR 3.51, 95% CI
      1.35-9.11), heart disease (HR 7.11, 95% CI, 2.89-17.51), cancer (HR 11.79, 95% CI
      4.95-28.03), and septic shock (HR 4.64, 95% CI 1.42-15.08) had higher association
      with mortality compared to other diagnoses. The risk factors significantly
      associated with mortality included older age (HR 1.01, 95% CI 1.00-1.08), lower
      hemoglobin level (HR 0.83, 95% CI 0.76-0.90), lower Glasgow Coma Scale (HR 0.66,
      95% CI 0.59-0.74), history of decreased urine output (HR 2.87, 95% CI 1.49-5.53),
      higher respiratory rate (HR 1.02, 95% CI 1.00-1.03), estimated glomerular
      filtration rate less than 60 ml/min/1.73m2 (binary) (HR 1.84, 95% CI 1.10-3.10),
      and lower oxygen saturation (HR 0.96, 95% CI 0.92-0.99). CONCLUSIONS: Post
      hospital mortality is disturbingly high among children 2-12 years of age in
      Tanzania. Post-hospital interventions are urgently needed especially for older
      children with chronic illnesses.

PMID- 30106988
TI  - Correction: Associated morphometric and geospatial differentiation among 98
      species of stone oaks (Lithocarpus).
AB  - [This corrects the article DOI: 10.1371/journal.pone.0199538.].

PMID- 30106989
TI  - Association between subclinical thyroid dysfunction and depressive symptoms in
      the Korean adult population: The 2014 Korea National Health and Nutrition
      Examination Survey.
AB  - BACKGROUND: Clinical hyper and hypothyroidism are associated with a risk for
      depression. OBJECTIVES: This study was performed to investigate the association
      between depressive symptoms and subclinical thyroid dysfunction. METHODS: Among
      the 7,550 subjects who participated in the 2014 Korea National Health and
      Nutrition Examination Survey, 1,763 participants without overt thyroid disease
      were included in this study. Serum thyroid stimulating hormone (TSH), serum free
      thyroxine (fT4), and depressive symptoms were analyzed based on the Patient
      Health Questionnaire (PHQ9). RESULTS: The percentages of subjects with
      subclinical hypothyroidism and subclinical hyperthyroidism were 3.3% and 2.6%,
      respectively. The percentages of subjects with moderate (10-14 points),
      moderately severe (15-19 points), and severe (>=20 points) depression according
      to the distribution of PHQ-9 scores were 4.7%, 1.1%, and 0.3%, respectively. TSH,
      fT4, and the percentage of patients with subclinical hypothyroidism were not
      significantly associated with PHQ-9 score. However, the percentage of patients
      with subclinical hyperthyroidism increased significantly with PHQ9 score (P =
      0.002). Subjects with subclinical hyperthyroidism had higher PHQ-9 scores than
      those with normal thyroid function (mean +/- standard error [SE], 4.2 +/- 0.5 vs.
      2.7 +/- 0.1 points, P = 0.010). More subjects with subclinical hyperthyroidism
      had a PHQ9 score >= 10 than did those with normal thyroid function (mean +/- SE,
      17.1 +/- 3.5 vs. 5.8 +/- 0.6%, P = 0.005). We performed logistic regression
      analyses for the presence of depressive symptoms, using age, sex, education,
      household income, alcohol drinking, smoking, diabetes, cerebrovascular disease
      history, subclinical hypothyroidism, and subclinical hyperthyroidism as
      variables. Subclinical hyperthyroidism was associated with the presence of
      clinically relevant depression (PHQ9 score >= 10), (odds ratio [OR], 4.04; 95%
      confidence interval [CI], 1.75-9.31; P = 0.001), and clinically significant
      depression (PHQ9 score >= 15), (OR, 7.05; 95% CI, 1.67-29.67; P = 0.008),
      respectively. However, subclinical hypothyroidism was not associated with the
      presence of clinically relevant depression (OR, 1.15; 95% CI, 0.39-3.38; P =
      0.800), or clinically significant depression (OR, 3.35; 95% CI, 0.71-15.79; P =
      0.127). CONCLUSIONS: We demonstrated that subclinical hyperthyroidism was
      independently associated with depressive symptoms in the Korean general
      population using national cross-sectional data.

PMID- 30106990
TI  - Comparison of motor skill learning, grip strength and memory recall on land and
      in chest-deep water.
AB  - Immersion in chest-deep water may augment explicit memory in healthy adults
      however, there is limited information on how this environment might affect
      implicit memory or motor learning. The purpose of this study was to compare the
      speed and accuracy for learning a motor skill on land and in chest-deep water.
      Verbal word recall and grip strength were included to gain a more complete
      understanding of the intervention. Sixty-two younger adults (age = 23.3 +/- 3.59
      yrs.) were randomly assigned to either a water group immersed to the xiphoid or a
      land group. Participants in both groups completed the same eight practice trials
      of a mirror-drawing task on two separate days. Outcome measures for this task
      included time and error numbers to complete each drawing. The number of words
      recalled using a 12 word recall test, and peak grip strength using a hand
      dynamometer were measured each day of testing. The influence of environment and
      repeated practice on each outcome measure were assessed with an analysis of
      variance and effect sizes (ES). Time and errors for both groups significantly
      decreased with practice (p < 0.01, ES = 0.11-0.28), however the drawing time was
      greater in water than on land for trials 1, 5, and 6 (ES = 0.50-0.55). There was
      a 7% increase in words recalled (9.24 +/- 1.19 vs 8.60 +/- 1.19) and a 16%
      increase in grip strength (405 +/- 104 vs 342 +/- 83) for water than land groups
      (ES 0.54-0.64). Healthy adults in chest-deep water and on land display comparable
      mirror-drawing speed and accuracy after minimal practice. Curiously, water
      immersion may augment verbal word recall and grip strength abilities.

PMID- 30106991
TI  - Effects of astigmatic defocus on binocular contrast sensitivity.
AB  - PURPOSE: To determine the effects of astigmatism on contrast sensitivity (CS).
      METHODS: Eighteen normal volunteers (30.5 +/- 6.0 [mean +/- SD] years) were
      recruited. After correcting each refractive error by spectacles, against-the-rule
      (ATR) or with-the-rule (WTR) astigmatism of +1.00, +2.00 and +3.00 D was
      intentionally produced in both eyes, and then binocular CS was measured. The
      cylindrical addition of different powers (+1.00-+3.00 D) was compensated with
      spherical lenses so that the spherical equivalent refraction became zero in each
      eye. Subsequently, the above cylindrical addition was monocularly induced, and
      binocular CS was measured again. The relation between CS and astigmatic power,
      axis, and monocular or binocular astigmatism was investigated. RESULTS: With
      binocular ATR and WTR astigmatism, increases in astigmatic power significantly
      correlated with decreases in the area under the log contrast sensitivity function
      (AULCSF). With monocular astigmatic defocus, astigmatic power addition did not
      affect AULCSF. With binocular astigmatic defocus of high-power (+2.00 and +3.00
      D), ATR astigmatism deteriorated AULCSF more than WTR astigmatism. In a
      comparison between binocular and monocular astigmatic defocus, CS was
      significantly worse with binocular astigmatic defocus than with monocular
      astigmatic defocus at higher spatial frequencies regardless of astigmatic power.
      CONCLUSIONS: Binocular astigmatic defocus deteriorates CS depending on the amount
      of astigmatic power. ATR astigmatism reduces CS more than WTR astigmatism dose.
      In addition, binocular astigmatic defocus affects CS more severely than monocular
      astigmatic defocus especially at high spatial frequencies.

PMID- 30106992
TI  - Morphological and micro-tomographic study on evolution of struvite in synthetic
      urine infected with bacteria and investigation of its pathological
      biomineralization.
AB  - Pathological biomineralization in the urinary system leads to urolithiasis.
      Formation of kidney stones involves a series of events during which they undergo
      morphological and mineralogical changes. We investigated the mineralization of
      biogenic struvite (in vitro) and examined the transformation of distinct interior
      and exterior structure of struvite. In vitro crystallization of struvite was
      performed in the presence of two bacteria that were originally isolated from the
      kidney stone patients. Morphological evaluation was carried out using SR-MUCT as
      well as FESEM, XRD and FT-IR. Characteristic internal 3-D morphology and porosity
      of the stones were studied. For comparison, patient derived struvite stones were
      used. From the results obtained, we report that the presence of bacteria enhances
      the crystallization process of struvite in vitro. A series of time-resolved
      experiments revealed that struvite crystals experienced a significant morphologic
      evolution from pin pointed structure to X-shaped and tabular morphologies. These
      X-shaped and unusual tabular habits of struvite resembled biogenic morphologies
      of struvite. SR-MUCT showed similarities between the patient derived and the in
      vitro derived struvite crystals. In conclusion, these experiments revealed that
      the bacteria play a major role in the specific morphogenesis of struvite and can
      able to control the nucleation, modulate crystalline phases, and shape of the
      growing crystal.

PMID- 30106993
TI  - DR1440 is a potential iron efflux protein involved in maintenance of iron
      homeostasis and resistance of Deinococcus radiodurans to oxidative stress.
AB  - Iron acquisition by bacteria is well studied, but iron export from bacteria is
      less understood. Herein, we identified dr1440 with a P-type ATPase motif as a
      potential exporter of iron from Deinococcus radiodurans, a bacterium known for
      its extreme resistance to radiation and oxidants. The DR1440 was located in cell
      membrane as demonstrated by fluorescence labelling analysis. Mutation of dr1440
      resulted in cellular accumulation of iron ions, and expression level of dr1440
      was up-regulated significantly under iron ion or hydrogen peroxide stress in the
      wild-type strain, implicating DR1440 as a potential iron efflux protein. The
      dr1440 mutant displayed higher sensitivity to iron ions and oxidative stresses
      including hydrogen peroxide, hypochlorous acid, and gamma-ray irradiation
      compared with the wild-type strain. The high amount of iron in the mutant strain
      resulted in severe protein carbonylation, suggesting that DR1440 might contribute
      to intracellular protein protection against reactive oxygen species (ROS)
      generated from ferrous ion-mediated Fenton-reaction. Mutations of S297A and C299A
      led to intracellular accumulation of iron, indicating that S297 and C299 might be
      important functional residues of DR1440. Thus, DR1440 is a potential iron efflux
      protein involved in iron homeostasis and oxidative stress-resistance of D.
      radiodurans.

PMID- 30106994
TI  - Oxytocin receptor is regulated by Peg3.
AB  - Mouse Peg3 encodes a DNA-binding protein involved in the milk letdown process. In
      the current study, we tested whether PEG3 controls the expression of the oxytocin
      receptor gene. According to the results, PEG3 directly binds to a genomic region
      within the 3rd exon of Oxtr, which contains a DNA-binding motif for PEG3. In
      nursing female mice, removal of PEG3 resulted in the increased expression of Oxtr
      in mammary epithelial cells and also in the hypothalamus. This suggests a
      repressor role of PEG3 in the expression of Oxtr in these tissues. Overall, this
      study suggests that Peg3 may function as a direct transcriptional regulator for
      Oxtr expression that acts to moderate the milk letdown process.

PMID- 30106995
TI  - Conservation of kinase-phosphorylation site pairings: Evidence for an
      evolutionarily dynamic phosphoproteome.
AB  - Kinase-mediated protein phosphorylation is a central mechanism for regulation of
      cellular responses and phenotypes. While considerable information is available
      regarding the evolutionary relationships within the kinase family, as well as the
      evolutionary conservation of phosphorylation sites, each aspect of this
      partnership is typically considered in isolation, despite their clear functional
      relationship. Here, to offer a more holistic perspective on the evolution of
      protein phosphorylation, the conservation of protein phosphorylation sites is
      considered in the context of the conservation of the corresponding modifying
      kinases. Specifically, conservation of defined kinase-phosphorylation site
      pairings (KPSPs), as well as of each of the component parts (the kinase and the
      phosphorylation site), were examined across a range of species. As expected,
      greater evolutionary distance between species was generally associated with lower
      probability of KPSP conservation, and only a small fraction of KPSPs were
      maintained across all species, with the vast majority of KPSP losses due to the
      absence of the phosphorylation site. This supports a model in which a relatively
      stable kinome promotes the emergence of functional substrates from an
      evolutionarily malleable phosphoproteome.

PMID- 30106997
TI  - Correction: Developmental milestones of the autonomic nervous system revealed via
      longitudinal monitoring of fetal heart rate variability.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0200799.].

PMID- 30106996
TI  - Nitrogen supply rate regulates microbial resource allocation for synthesis of
      nitrogen-acquiring enzymes.
AB  - Although microorganisms will preferentially allocate resources to synthesis of
      nitrogen (N)-acquiring enzymes when soil N availability is low according to the
      resource allocation model for extracellular enzyme synthesis, a robust link
      between microbial N-acquiring enzyme activity and soil N concentration has not
      been reported. To verify this link, we measured several indices of soil N
      availability and enzyme activity of four N-acquiring enzymes [N-acetyl-beta
      glucosaminidase (NAG), protease (PR), urease (UR), and L-asparaginase (LA)] and a
      carbon (C)-acquiring enzyme [beta-D-glucosidase (BG)] in arable and forest soils.
      Although the ratios of NAG/BG and PR/BG were not significantly related with
      indices of soil N availability, ratios of LA/BG and UR/BG were strongly and
      negatively related with potentially mineralizable N estimated by aerobic
      incubation but not with pools of labile inorganic N and organic N. These results
      suggest that microorganisms might allocate their resources to LA and UR synthesis
      in response to N supply rate rather than the size of the easily available N
      pools. It was also suggested that the underlying mechanism for synthesis was
      different between these N-acquiring enzymes in soil microorganisms: microbial LA
      and UR were primarily synthesized to acquire N, whereas NAG and PR syntheses were
      regulated not only by N availability but also by other factors.

PMID- 30106998
TI  - Assessment of hypertension chronic care model: Pacic application in Bosnia and
      Herzegovina.
AB  - The objectives of this study were to evaluate patients' attitudes towards
      hypertension treatment according to the chronic care model and to assess the
      implementation of hypertension clinical guidelines in family medicine. The cross
      sectional study was carried out in two randomly selected primary health care
      centers (Bijeljina and Prijedor), respectively in Bosnia and Herzegovina,
      covering the period between March and April 2016. This study sample consists of
      791 respondents with hypertension purposing to measure specific actions and
      quality of care for hypertensive patients. The Patient Assessment of Chronic
      Illness Care (PACIC) was used. Treatment for the indicators of hypertension was
      assessed by analyzing patients' medical charts according to the recommendations
      of clinical guidelines. More than half of the evaluated indicators of treatment
      for hypertension were documented in medical charts of 84.07% patients. The
      average overall PACIC score was 4.18 (SD 0.59), being an average of the separate
      scores of 4.19 (SD 0.57) in men and 4.17 (SD 0.60) in women. Subscale means of
      PACIC were as follows: patient activation 4.33, delivery system design 4.36; goal
      setting 4.03; problem solving 4.51; follow-up and co-ordination 3.67. No
      statistically significant correlations in the overall score and subscale scores
      were found by demographic characteristics. Non-smokers had a significantly higher
      overall score compared to smokers (p = 0.001). As implementation of the
      guidelines became stronger, the reported PACIC scores rose. Continuing the
      education of patients in order to achieve better health care outcomes is
      imperative.

PMID- 30106999
TI  - Willingness to pay and moral stance: The case of farm animal welfare in Germany.
AB  - This study examines the impact of ethical attitude on the willingness to pay for
      farm animal welfare improvement in Germany. Little is known about the pluralism
      of moral attitudes that may exist behind farm animal welfare issues and its
      relationship to customers' willingness to pay for it. Via a large survey (n =
      1334) we are able to identify different moral dimensions by employing validated
      scales. We find utilitarian alongside deontological attitudes as well as a
      mixture of both. Thus, presupposing a standard moral attitude is too simple. This
      has implications for decision-making on markets, since the implicit normative
      assumptions of a utilitarian position in economics has to be critically assessed.
      Furthermore, we asked for the willingness to pay for various aspects of farm
      animal welfare improvement. We find significant positive correlations between
      willingness to pay and environmental concern, altruism and less apathy. Measured
      in Euro, a higher environmental concern has the strongest effect on WTP for all
      five moral scales. Outliers with higher bids are willing to pay almost five times
      for any aspect of farm animal welfare than the rest of the sample. A more
      detailed analysis of outliers demonstrates that market-based approaches have
      restrictions in capturing certain moral values. Moreover, the motivations behind
      zero bids reveal that moral concerns outweigh indifference towards animal welfare
      by far. This has implications how policy can be designed to serve people's demand
      for higher animal welfare standards. Two other findings are of interest. First,
      we find a very high number of people assigning an intrinsic value to animals
      (90%). Second, zero bids and outlier treatment in WTP-studies deserves more
      careful consideration, since WTP-estimates are easily skewed by excluding these
      groups.

PMID- 30107000
TI  - Correction: Optical imaging of ovarian cancer using a matrix metalloproteinase-3
      sensitive near-infrared fluorescent probe.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0192047.].

PMID- 30107001
TI  - Robustness of individual differences in temporal interference effects.
AB  - Magnitudes or quantities of the different dimensions that define a stimulus
      (e.g., space, speed or numerosity) influence the perceived duration of that
      stimulus, a phenomenon known as (temporal) interference effects. This complicates
      studying the neurobiological foundation of the perception of time, as any
      signatures of temporal processing are tainted by interfering dimensions. In
      earlier work, in which judgements on either time or numerosity were made while
      EEG was recorded, we used Maximum Likelihood Estimation (MLE) to estimate, for
      each participant separately, the influence of temporal and numerical information
      on making duration or numerosity judgements. We found large individual
      differences in the estimated magnitudes, but ML-estimates allowed us to partial
      out interference effects. However, for such analyses, it is essential that
      estimates are meaningful and stable. Therefore, in the current study, we examined
      the reliability of the MLE procedure by comparing the interference magnitudes
      estimated in two sessions, spread a week apart. In addition to the standard
      paradigm, we also presented task variants in which the interfering dimension was
      manipulated, to assess which aspects of the numerosity dimension exert the
      largest influence on temporal processing. The results indicate that individual
      interference magnitudes are stable, both between sessions and over tasks.
      Further, the ML-estimates of the time-numerosity judgement tasks were predictive
      of performance in a standard temporal judgement task. Thus, how much temporal
      information participants use in time estimations tasks seems to be a stable trait
      that can be captured with the MLE procedure. ML-estimates are, however, not
      predictive of performance in other interference-tasks, here operationalized by a
      numerical Stroop task. Taken together, the MLE procedure is a reliable tool to
      quantify individual differences in magnitude interference effects and can
      therefore reliably inform the analysis of neuroimaging data when contrasts are
      needed between the accumulation of a temporal and an interfering dimension.

PMID- 30107002
TI  - Vanishing industries and the rising monopoly of universities in published
      research.
AB  - Anecdotes abound regarding the decline of basic research in industrial and
      governmental settings, but very little empirical evidence exists about the
      phenomenon. This article provides a systematic and historical analysis of the
      contribution of various institutional sectors to knowledge production at the
      world and country levels across the past four decades. It highlights a dramatic
      decline in the diffusion of basic research by industrial and governmental sectors
      across all countries-with a corresponding increase in the share from universities
      as well as an increase of partnerships between universities and other sectors.
      Results also shows an increase in the relative share of industries in applied
      research, as measured through patents. Such divergence in university and industry
      research activities may hinder industries' ability to translate basic knowledge
      into technological innovation, and could lead to a growing misalignment between
      doctoral training and future job expectations. Industries and universities must
      rethink strategies for partnerships and publishing to maximize scientific
      progress and to ensure the greatest gains for society.

PMID- 30107003
TI  - The vitamin D receptor gene as a determinant of survival in pancreatic cancer
      patients: Genomic analysis and experimental validation.
AB  - PURPOSE: Advanced pancreatic cancer is a highly refractory disease almost always
      associated with survival of little more than a year. New interventions based on
      novel targets are needed. We aim to identify new genetic determinants of overall
      survival (OS) in patients after treatment with gemcitabine using genome-wide
      screens of germline DNA. We aim also to support these findings with in vitro
      functional analysis. PATIENTS AND METHODS: Genome-wide screens of germline DNA in
      two independent cohorts of pancreatic cancer patients (from the Cancer and
      Leukemia Group B (CALGB) 80303 and the Mayo Clinic) were used to select new genes
      associated with OS. The vitamin D receptor gene (VDR) was selected, and the
      interactions of genetic variation in VDR with circulating vitamin D levels and
      gemcitabine treatment were evaluated. Functional effects of common VDR variants
      were also evaluated in experimental assays in human cell lines. RESULTS: The
      rs2853564 variant in VDR was associated with OS in patients from both the Mayo
      Clinic (HR 0.81, 95% CI 0.70-0.94, p = 0.0059) and CALGB 80303 (HR 0.74, 0.63
      0.87, p = 0.0002). rs2853564 interacted with high pre-treatment levels of 25
      hydroxyvitamin D (25(OH)D, a measure of endogenous vitamin D) (p = 0.0079 for
      interaction) and with gemcitabine treatment (p = 0.024 for interaction) to confer
      increased OS. rs2853564 increased transcriptional activity in luciferase assays
      and reduced the binding of the IRF4 transcription factor. CONCLUSION: Our
      findings propose VDR as a novel determinant of survival in advanced pancreatic
      cancer patients. Common functional variation in this gene might interact with
      endogenous vitamin D and gemcitabine treatment to determine improved patient
      survival. These results support evidence for a modulatory role of the vitamin D
      pathway for the survival of advanced pancreatic cancer patients.

PMID- 30107004
TI  - Laboratory evaluation of the effects of sterilizing doses of gamma-rays from
      Caesium-137 source on the daily flight activity and flight performance of Aedes
      albopictus males.
AB  - The control of Aedes albopictus through Sterile Male Releases requires that the
      most competitive males be mass-reared and sterilized usually with gamma- or X-ray
      radiation prior to release. Developing an understanding of the impact of
      irradiation treatment on flight performance in sterile males is very important
      because any fitness cost may reduce the efficacy of SIT intervention in the
      field. Here, we examined the role of irradiation exposure and sugar-feeding on
      daily flight activity and performance of Ae. albopictus males sterilized during
      pupal stage with gamma-radiation at 35Gray from a Caesium 137 source. We used a
      previously developed automated video tracking system to monitor the flight
      activity of different groups of sterile and control non-sterile males over 24
      hours in a flight arena. This monitoring took place under controlled laboratory
      conditions and we wished to quantify the daily flight activity and to highlight
      any changes due to radiation treatment and nutritional conditions (starved versus
      sugar fed). Our experimental evidence demonstrated a characteristic diurnal
      flight activity with a bimodal pattern regardless of the treatment. Precisely,
      both irradiated and non-irradiated males exhibited two distinct peaks in flight
      activity in the morning (6-8 a.m.) and late afternoon (4-6 p.m.). Under changing
      physiological conditions, irradiated males were generally more active over time
      and flew longer overall distances than control male populations. These results
      suggest some internal circadian control of the phase relation to the light-dark
      cycle, with evidence for modification of flight performance by nutritional
      status. The fact that daily activity patterns are alike in irradiated and control
      Ae. albopictus males, and that sterile males could display higher flight
      performance, is in contrast with the hypothesis that irradiation treatment
      appears to reduce the fitness of male mosquitoes. We discuss the implications of
      the present study in sterile-male release programs against Ae. albopictus.

PMID- 30107006
TI  - Palilalia due to steroid-responsive encephalopathy.

PMID- 30107005
TI  - Effects of fertilizer application schemes and soil environmental factors on
      nitrous oxide emission fluxes in a rice-wheat cropping system, east China.
AB  - Nitrous oxide (N2O) is a potent greenhouse gas (GHG) with agricultural soils
      representing its largest anthropogenic source. However, the mechanisms involved
      in the N2O emission and factors affecting N2O emission fluxes in response to
      various nitrogenous fertilizer applications remain uncertain. We conducted a four
      year (2012-2015) field experiment to assess how fertilization scheme impacts N2O
      emissions from a rice-wheat cropping system in eastern China. The fertilizer
      treatments included Control (CK), Conventional fertilizer (CF), CF with shallow
      irrigation (CF+SI), CF with deep-irrigation system (CF+DI), Optimized fertilizer
      (OF), OF with Urease inhibitor (OF+UI), OF with conservation tillage (OF+CT) and
      Slow-release fertilizer (SRF). N2O emissions were measured by a closed static
      chamber method. N2O emission fluxes ranged from 0.61 MUg m-2 h-1 to 1707 MUg m-2
      h-1, indicating a significant impact of nitrogen fertilizer and cropping type on
      N2O emissions. The highest crop yields for wheat (3515-3667 kg ha-1) and rice
      (8633-8990 kg ha-1) were observed under the SRF and OF+UI treatments with
      significant reduction in N2O emissions by 16.94-21.20% and 5.55-7.93%,
      respectively. Our findings suggest that the SRF and OF+UI treatments can be
      effective in achieving maximum crop yield and lowering N2O emissions for the rice
      wheat cropping system in eastern China.

PMID- 30107007
TI  - Restless mouth syndrome.

PMID- 30107008
TI  - Unruptured intracranial aneurysms and life insurance underwriting.
AB  - Unruptured intracranial aneurysms are common. Rupture is rare, but associated
      with considerable morbidity and mortality. Screening for unruptured intracranial
      aneurysms is indicated in certain patient populations, but many patients request
      screening outside of established guidelines. In addition, intracranial aneurysms
      may be discovered incidentally. The presence of an intracranial aneurysm has a
      negative effect for the patient seeking life insurance. This commentary provides
      a perspective on insurance underwriting in individuals with unruptured
      intracranial aneurysms and offers points for clinicians to consider when
      counseling patients seeking screening.

PMID- 30107009
TI  - Diagnostic test results in primary CNS vasculitis: A systematic review of
      published cases.
AB  - Background: Primary CNS vasculitis (PCNSV) can be diagnosed using cerebral
      angiography or histopathology combined with clinical features. The original
      diagnostic criteria, which weigh each test equally, have not been validated.
      Limited sensitivity and specificity for biopsy and angiography are recognized. We
      systematically reviewed results of diagnostic tests performed in patients with an
      ultimate diagnosis of PCNSV. Methods: We searched the OVID Medline database and
      bibliographies for original cases of PCNSV. We recorded demographics, diagnostic
      tests used, and assessed agreement between angiography and biopsy when both tests
      were performed. We also recorded MRI and CSF results. Results: We found 701
      original cases with PCNSV diagnosed with angiography or pathology. A total of 269
      patients (38.4%) had both cerebral angiography and histopathologic testing
      (biopsy/postmortem). Classic angiographic features of vasculitis were associated
      with pathologic confirmation in just 32 patients (4.6%). Seventy-four patients
      (10.6%) with any abnormality on angiography had a normal biopsy, and 99 patients
      (14.1%) with abnormal biopsies had normal angiography. Brain MRI was abnormal in
      505/541 patients (93.3%) and CSF was abnormal in 360/484 patients (74.4%).
      Increasing use of angiography and decreasing histopathologic testing were found
      over time. Conclusions: Cerebral angiography and pathologic tissue examination
      were undertaken in a minority of published cases with a diagnosis of PCNSV. When
      both diagnostic tests were performed, disagreement between them was more than 5
      times more likely than agreement. Diagnostic criteria for PCNSV may require
      revision to classify the clinical, pathologic, and radiologic features of this
      condition more accurately.

PMID- 30107010
TI  - The use of ultrasound in neuromuscular diagnoses.
AB  - Purpose of review: The use of ultrasonography for diagnosis of neuromuscular
      disorders is a relatively new but rapidly expanding field. This review covers key
      ultrasound findings in primary disease of muscle and nerve. Recent findings:
      Ultrasonography is used routinely for evaluation of entrapment neuropathies,
      hereditary and inflammatory neuropathies, polyneuropathies, myopathies, and motor
      neuron disease. When used in association with other electrodiagnostic testing,
      ultrasound has allowed physicians to increase the yield of clinical evaluation in
      diagnostic laboratories. Summary: While ultrasonography has not yet replaced the
      need for electrodiagnostic studies, it has become a useful accompaniment.

PMID- 30107011
TI  - Preoperative evaluation for epilepsy surgery: Process improvement.
AB  - Background: Epilepsy surgery (ES) can improve seizure outcome. A prolonged
      duration of presurgical evaluation contributes to epilepsy-related morbidity and
      mortality. We introduced process changes to decrease evaluation time (ET) and
      increase ES numbers (excluding vagus nerve stimulation). Methods: The University
      of Colorado Hospital patient database was searched for ESs between January 2009
      and May 2016. Measures to reduce ET included (1) increasing patient care
      conference (PCC) frequency; (2) faster intracarotid amobarbital test (IAT)
      scheduling; (3) dedicated ES clinic; and (4) adding a nurse navigator. ET from
      noninvasive video-EEG monitoring (P1) to IAT, PCC, and ES, and ES volume were
      determined and compared for a baseline group (P1 January 2009-March 2013) and a
      group exposed to process changes (P1 after March 2013), the postchanges group, to
      assess the effect of these measures. Results: ES number was 61 for the baseline
      group and 77 for the postchanges group, increasing the annual rate at 3 years
      after changes from 14.4 to 36.8 (p = 0.0008; 37% yearly increase postchanges).
      Interventions lowered average ET by 96 days (p <= 0.0001), P1 to IAT by 39 days
      (p = 0.0011), and P1 to PCC by 58 days (p = 0.0002). Conclusions: Simple process
      changes, including more frequent patient care conferences, faster scheduling, a
      dedicated ES clinic, and a nurse navigator significantly decreased evaluation
      times and increased ES numbers. Centers could utilize similar strategies to
      improve process and surgical volume and thereby increase patient seizure control
      and safety.

PMID- 30107012
TI  - Manipulating the nervous system: The brave new world.

PMID- 30107013
TI  - The emerging partnership between palliative care and stroke.

PMID- 30107014
TI  - Neurologic diseases in ancient Roman sculpture busts.

PMID- 30107015
TI  - Standard strategies for diagnosis and treatment of patients with newly diagnosed
      Parkinson disease.

PMID- 30107016
TI  - Disease-modifying therapies for nonrelapsing multiple sclerosis: Costs and
      benefits of medical intervention.

PMID- 30107017
TI  - B lymphoblastic leukemia/lymphoma presenting as seventh cranial nerve palsy.

PMID- 30107018
TI  - Parkinsonism-hyperpyrexia syndrome: Broadening our differential diagnosis in the
      ICU.

PMID- 30107019
TI  - Recommendations for the safe administration of donepezil.

PMID- 30107020
TI  - The value of the neurologist.

PMID- 30107021
TI  - Disease-modifying therapies for nonrelapsing multiple sclerosis: Absence of
      evidence does not constitute evidence of absence.

PMID- 30107023
TI  - Standard strategies for diagnosis and treatment of patients with newly diagnosed
      Parkinson disease: UNITED STATES.

PMID- 30107022
TI  - Vestibular signs of thiamine deficiency during the early phase of suspected
      Wernicke encephalopathy.
AB  - Non-encephalopathic presentations of CNS thiamine deficiency may be difficult to
      diagnose. We describe neuro-otologic findings of Wernicke syndrome in 5 patients
      with vestibular manifestations. Diagnosis was confirmed by low serum levels,
      response to replacement, and brain MRI to exclude other causes. All had
      bilaterally abnormal horizontal head impulse vestibulo-ocular reflex (VOR)
      responses and pathologic gaze-evoked nystagmus, without encephalopathy. After
      thiamine replacement, 4 had total resolution of vestibular and oculomotor
      findings. Novel findings included 2 patients whose VOR function improved within
      minutes of IV repletion and 1 whose recovery was documented by serial
      quantitative recordings. Early diagnosis of Wernicke by examining vestibular
      reflexes and prompt IV treatment might prevent encephalopathy and other
      neurologic or systemic complications of thiamine depletion.

PMID- 30107024
TI  - The financial contribution of the multiple sclerosis specialist.
AB  - Purpose of review: To examine the financial effect of the multiple sclerosis (MS)
      specialist on the academic health center (AHC). Recent findings: Using data
      derived from an academic MS center with respect to patient numbers and practice
      pattern regarding diagnostic studies and disease-modifying therapies (DMT)
      coupled with reasonable assumptions regarding the profit margin for tests and
      treatments, 1 full-time MS specialist (1 clinical full-time equivalent [cFTE])
      may annually generate downstream revenue exceeding $8,000,000. If all diagnostic
      studies and therapies were obtained at the facility, the potential revenue
      generated for the facility can exceed $25,000,000 per 1 cFTE. These calculations
      do not include the professional net revenue generated by referrals to other
      professionals. Summary: With current models of reimbursement for health care, the
      MS specialist provides an enormous potential source of revenue for the AHC. This
      information is critically important in obtaining institutional support for the
      provision of labor-intensive MS care.

PMID- 30107025
TI  - The practice of neuroimaging within a neurology office setting.
AB  - Imaging is an essential tool in the diagnosis and management of neurologic
      disorders, yet its adoption in the clinical neurology setting is limited.
      Perceived cost barriers and political pressures have caused undue apprehension
      for a community of experts that otherwise plays a leadership role in solving
      complex neurologic puzzles. Some private practice neurologists have integrated
      advanced imaging services into a comprehensive neuroservices model, demonstrating
      its plausibility together with a recipe for success. The purpose of this article
      is to explore the advantages, disadvantages, and considerations for integrating
      imaging into an outpatient neurology clinic. Clinical and business advantages are
      weighed against financial, regulatory, and political risks.

PMID- 30107026
TI  - Disaster neurology: A new practice opportunity and challenge for the neurologist.
AB  - Headlines are filled with stories of the physical disability and loss of life
      that results from both natural and man-made disasters. The role of a neurologist
      as part of the response to these tragedies has moved from a supportive role to
      the front line. Recent earthquakes in Haiti and Japan as well as military
      conflicts in Iraq and Afghanistan have demonstrated an increased need for
      nonsurgical neurologic care. Disaster neurology has become attractive to
      neurologists at many stages of their careers. Employed, academic, and private
      practice neurologists all have the potential to embrace this opportunity to apply
      their clinical skills to help others in need of care. Neurologists interested in
      engaging in disaster relief efforts should have the ability to respond to a
      situation quickly with the flexibility of devoting several weeks to the response
      effort.

PMID- 30107027
TI  - Multimorbidity in patients with chronic migraine and medication overuse headache.
AB  - OBJECTIVES: Patients with chronic migraine (CM) display a considerable amount of
      comorbidities, particularly psychiatric and cardiovascular, and the presence of
      multiple comorbidities, that is, the so-called multimorbidity, is a risk factor
      for migraine chronification or maintenance of CM. Our aim was to address the rate
      and impact of multimorbidity in patients with CM and medication overuse headache
      (MOH). MATERIALS & METHODS: In a sample of patients with CM attending a
      structured withdrawal for coexisting MOH, we defined multimorbidity as the
      presence of two or more conditions in addition to CM-MOH. We compared patients
      with and without multimorbidity for demographic and clinical variables, quality
      of life, and disability; we also tested whether patients with multimorbidity had
      higher likelihood to attend emergency room, relapse into CM, and require further
      withdrawal treatments by 12 months. RESULTS: One hundred and ninety-four patients
      were enrolled as follows: 61% had at least one comorbidity, the most common being
      mental (34%), circulatory (18%), and endocrine conditions (13%); 32% were
      multimorbidity cases. Patients with multimorbidity had higher headaches
      frequency, older age, lower education and lower employment rates, higher
      disability and lower QoL. They were more frequently opioids/barbiturates
      overusers and were more likely to attend ER (OR: 2.36), relapse into CM (OR:
      2.19), and undergo another withdrawal (OR: 2.75) by 12 months after discharge,
      after controlling for age, gender, years of education, and headache frequency.
      CONCLUSIONS: Recognizing multimorbidity in patients with CM-MOH is important to
      enhance the management of these complex patients, who are at risk of polypharmacy
      and increased health care utilization.

PMID- 30107028
TI  - Gender-affirming hormone therapy and the risk of sex hormone-dependent tumours in
      transgender individuals-A systematic review.
AB  - BACKGROUND: Cancers are a leading cause of death worldwide, and transgender
      individuals are no exception. The effects of gender-affirming hormone therapy
      (GAHT) on sex hormone-dependent tumours are unclear. Therefore, this review seeks
      to determine whether tumour risk in transgender individuals differs from the
      general population, to guide clinical screening recommendations. METHODS: We
      performed a systematic review based on the PRISMA guidelines. MEDLINE, Embase and
      PsycINFO databases were searched for studies examining tumour incidence,
      prevalence or cancer-related mortality in transgender individuals. All English
      peer-reviewed publications were included if histological type and temporal
      relation to GAHT were reported. Case reports were included if there were >=2
      cases of the same histological type. RESULTS: The search strategy identified 307
      studies. Excluding those that did not meet inclusion criteria, 43 studies (7
      cohort studies, 2 cross-sectional studies and 34 case reports) were reviewed.
      Retrospective cohort studies suggest no increase in risk of tumour development in
      transgender individuals receiving GAHT compared to the general population.
      Notably, the mean ages of cohorts were young and were treated with GAHT for
      insufficient durations to assess tumour risk. Case reports raise potential
      associations between high-dose oestradiol and anti-androgen therapy with
      prolactinoma and meningioma, respectively. CONCLUSIONS: Further longitudinal
      studies are required to assess the risk of GAHT and hormone-dependent tumour
      development. Until further evidence is available, tumour screening should be
      based on guidelines for the general population and the presence of organs in
      transgender individuals rather than gender identity or hormonal therapy status.

PMID- 30107030
TI  - Mapping, in vivo, the uniformity of two skin properties alongside the human face
      by a 3D virtual approach.
AB  - OBJECTIVE: To determine the homogeneity in the distribution of two cutaneous
      functions (hydration and elasticity) along the entire human face. MATERIAL AND
      METHODS: The half faces (right or left, randomly chosen) of two groups of
      Caucasian women were measured on 24 different small sites (elasticity) and 41
      others (hydration), by instruments of small-sized probes (Cutometer(r) and
      Corneometer(r) , respectively). Hydration of the face was recorded at different
      times (up to 24 h), post application of a highly hydrating product. The recorded
      values (left and right half faces) were further gathered and digitally positioned
      on a virtual feminine face and their intensity was illustrated through a colored
      white (lower values)-blue (higher values) scale. RESULTS: The reconstitution of
      the mapping of the two measured parameters (from the left and right sides of
      different subjects), shows a perfect symmetry vis a vis the nose axis. However,
      both parameters present slightly variable but significant values along the human
      face. Sites from the temple are less elastic than chin or forehead. The upper and
      lower parts of the forehead show slight disparities in their elasticity values.
      Cheeks are significantly less prone at retaining their imparted hydration status
      (lost 2 h after application of a hydrating product) as compared to sub-ocular
      regions or chin that retain their hydration up to 24 h. Attempts to establish a
      mutual relationship between the two skin properties unsurprisingly failed.
      CONCLUSION: The two studied skin properties show a slight but highly symmetric
      disparity along the entire human face.

PMID- 30107029
TI  - Potentiation of the cystic fibrosis transmembrane conductance regulator by VX-770
      involves stabilization of the pre-hydrolytic, O1 state.
AB  - BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is a debilitating hereditary disease
      caused by mutations in the cystic fibrosis transmembrane conductance regulator
      (CFTR) gene, which encodes an anion channel. Wild type-CFTR gating is a non
      equilibrium process. After ATP binding, CFTR enters a stable open state (O1 ).
      ATP hydrolysis leads it to a short-lived post-hydrolytic open state (O2 ), from
      which channels close. Here, we use mutations to probe the mechanism of VX-770,
      the first compound directly targeting the CFTR protein approved for treatment of
      CF. D1370N and K1250R mutations reduce or abolish catalytic activity, simplifying
      the gating scheme to an equilibrium (C<->O1 ); K464A-CFTR has a destabilized O1
      state and rarely closes via hydrolysis. EXPERIMENTAL APPROACH: Potentiation by VX
      770 was measured using microscopic imaging of HEK293 cells expressing an anion
      sensitive YFP-CFTR. A simple mathematical model was used to predict fluorescence
      quenching following extracellular iodide addition and estimate CFTR conductance.
      Membrane density of CFTR channels was measured in a parallel assay, using CFTR
      pHTomato. KEY RESULTS: VX-770 strongly potentiated WT-CFTR, D1370N-CFTR and
      K1250R-CFTR. K464A-CFTR was also strongly potentiated, regardless of whether it
      retained catalytic activity or not. CONCLUSIONS AND IMPLICATIONS: Similar
      potentiation of hydrolytic and non-hydrolytic mutants suggests that VX-770
      increases CFTR open probability mainly by stabilizing pre-hydrolytic O1 states
      with respect to closed states. Potentiation of K464A-CFTR channels suggests
      action of VX-770 did not strongly alter conformational dynamics at site 1.
      Understanding potentiator mechanism could help develop improved treatment for CF
      patients. The fluorescence assay presented here is a robust tool for such
      investigations.

PMID- 30107032
TI  - Current State of Microbicide Development.
AB  - Efforts in developing an effective vaccine for human immunodeficiency virus (HIV)
      has been challenging as HIV strains are highly variable and exhibit extraordinary
      mutability. Despite condom usage and pre-exposure prophylaxis as excellent
      prevention strategies, lack of accessibility in some developing countries and low
      adherence due to sociocultural factors continue to act as barriers in reducing
      the HIV epidemic. Microbicides are topical therapies developed to prevent HIV and
      other sexually transmitted infections during intercourse. Microbicides applied
      vaginally or rectally are intended to prevent HIV infection at the site of
      transmission by either inhibiting its entry into immune cells or prevent viral
      replication. This review will summarize some of the current state-of-the-art
      microbicide formulations that are in preclinical and clinical stages of
      development and discuss some of the challenges associated with microbicide
      development.

PMID- 30107031
TI  - Plant and algal chlorophyll synthases function in Synechocystis and interact with
      the YidC/Alb3 membrane insertase.
AB  - In the model cyanobacterium Synechocystis sp. PCC 6803, the terminal enzyme of
      chlorophyll biosynthesis, chlorophyll synthase (ChlG), forms a complex with high
      light-inducible proteins, the photosystem II assembly factor Ycf39 and the
      YidC/Alb3/OxaI membrane insertase, co-ordinating chlorophyll delivery with
      cotranslational insertion of nascent photosystem polypeptides into the membrane.
      To gain insight into the ubiquity of this assembly complex in higher
      photosynthetic organisms, we produced functional foreign chlorophyll synthases in
      a cyanobacterial host. Synthesis of algal and plant chlorophyll synthases allowed
      deletion of the otherwise essential native cyanobacterial gene. Analysis of
      purified protein complexes shows that the interaction with YidC is maintained for
      both eukaryotic enzymes, indicating that a ChlG-YidC/Alb3 complex may be
      evolutionarily conserved in algae and plants.

PMID- 30107033
TI  - Cytotoxic and Photocytotoxic Effects of Cercosporin on Human Tumor Cell Lines.
AB  - Cercosporin is a naturally occurring perylenequinone. Although other
      perylenequinones have been extensively studied as photosensitizers in
      photodynamic therapy of cancer (PDT), cercosporin has been studied in this light
      only within the remits of phytopathology. Herein, we investigated the
      photocytotoxicity of cercosporin against two glioblastoma multiforme (T98G and
      U87) and one breast adenocarcinoma (MCF7) human cell lines. Cercosporin was found
      to be a potent singlet oxygen producer upon 532 nm excitation, while its cell
      loading was similar for MCF7 and U87, but approximately threefold higher for T98G
      cells. The subcellular localization of cercosporin was in all cases in both
      mitochondria and the endoplasmic reticulum. Light irradiation of cercosporin
      incubated cells around 450 nm showed that T98G cells were more susceptible to
      cercosporin PDT, mainly due to their higher cercosporin uptake. Metabolic studies
      before and 1 h following cercosporin PDT showed that cercosporin PDT instigated a
      bioenergetic collapse in both the respiratory and glycolytic activities of all
      cell lines. In the dark, cercosporin exhibited a synergistic cytotoxicity with
      copper only in the most respiratory cell lines (MCF7 and T98G). Cercosporin is a
      potent photosensitizer, but with a short activation wavelength, mostly suitable
      for superficial PDT treatments, especially when it is necessary to avoid
      perforations.

PMID- 30107034
TI  - Using Real-World Data to Extrapolate Evidence From Randomized Controlled Trials.
AB  - Randomized controlled trials (RCTs) provide evidence for regulatory agencies,
      shape clinical practice, influence formulary decisions, and have important
      implications for patients. However, many patient groups that are major consumers
      of drugs are under-represented in randomized trials. We review three methods to
      extrapolate evidence from trial participants to different target populations
      following market approval and discuss how these could be implemented in practice
      to support regulatory and health technology assessment decisions. Although these
      methods are not a substitute for less restrictive pre-approval RCTs or rigorous
      observational studies when sufficient data are available in the post-approval
      setting, they can help to fill the evidence gap that exists in the early
      marketing period. Early evidence using real-world data and methods for
      extrapolating evidence should be reported with clear explanation of assumptions
      and limitations especially when used to support regulatory and health technology
      assessment decisions.

PMID- 30107035
TI  - Indications for root canal treatment in a Swedish county dental service: patient-
      and tooth-specific characteristics.
AB  - AIM: To study patient- and tooth-specific characteristics of teeth indicated for
      root canal treatment, in the public dental service of the county of Vastra
      Gotaland, Sweden. METHODOLOGY: During a designated 8-week period, general dental
      practitioners working at 20 different public dental clinics consecutively
      registered indications for undertaking root canal treatment. The patients'
      subjective level of pain was also registered (visual analogue scale) at the very
      first appointment. The following information was retrieved from computerized
      dental records and radiographs: gender, age, number of remaining teeth, tooth
      group, previous restoration, number of restored surfaces, dental caries and tooth
      substance loss. Gender and age were compared using both descriptive and
      analytical statistics. RESULTS: The material comprised 243 teeth in 243 patients:
      128 (52.7%) women and 115 (47.3%) men, mean age 48.3 years. Molar teeth
      predominated (47.7%). Most of the teeth (83.5%) had previously been restored and
      exhibited significant loss of tooth substance, more than a third of the crown
      (71.3%). Dental caries was present in 127 teeth (62.9%). Dental trauma was
      implicated in only seven cases (2.9%). Initial treatment was frequently
      undertaken at an emergency visit, for relief of symptoms (64.9%). The most
      commonly registered indication was pulpal necrosis with apical periodontitis
      (38.1%), followed by pulpitis (37.7%). Retreatment of a root filled tooth was
      reported in 18 teeth (7.4%). CONCLUSIONS: In the general Public Dental Service of
      Sweden, root canal treatment is most frequently undertaken in molars. The primary
      indication is relief of symptoms. Retreatment of root filled teeth is uncommon.

PMID- 30107036
TI  - Ultrasound-assisted Synthesis of Ag-ZnS/rGO and its Utilization in Photocatalytic
      Degradation of Tetracycline Under Visible Light Irradiation.
AB  - Recent improvements based on heterojunction nanocomposites have opened new
      possibilities in photocatalysis. In this research, an ultrasound-assisted
      coprecipitation method was used to fabricate silver, zinc sulfide and reduced
      graphene oxide (Ag-ZnS/rGO) nanocomposite, and characterization results indicated
      that 3% Ag-ZnS spherical nanoparticles are successfully embedded in rGO matrix.
      The potential of the Ag-ZnS/rGO, as a visible light active photocatalyst, was
      assessed through optimizing degradation of Tetracycline (TC) by response surface
      methodology. It was found that the photocatalytic degradation of TC increased
      with an increase in the amount of nanocomposite and irradiation time, whereas it
      decreased with increasing the initial TC concentration. Under the optimal
      conditions (10 mg L-1 of TC, 1.25 g L-1 of Ag-ZnS/rGO, at pH = 7, and irradiation
      duration 110 min), more than 90% of the TC was degraded. The study of the
      mechanism of the photocatalytic process disclosed that the synergistic role of
      surface plasmon resonance (SPR) induced by Ag nanoparticles and p-type
      semiconductor feature of rGO leads to ZnS semiconductor stimulation in the
      visible light region. Eventually, a pseudo-first order kinetics model was
      developed based on the proposed mechanism. The obtained results highlight the
      role of Ag-ZnS/rGO nanophotocatalyst toward degradation of some antibiotics under
      visible light.

PMID- 30107037
TI  - Assessment of artefacts produced by metal posts on CBCT images.
AB  - AIM: To evaluate artefact intensity in cone beam computed tomography (CBCT)
      images of two alloys used in metal posts scanned using different exposure
      parameters. METHODOLOGY: The sample consisted of 20 single-rooted teeth divided
      into two groups for use with either a NiCr post or AgPd post. All teeth were
      scanned with and without their corresponding metal posts and with and without the
      presence of an extra restored tooth in the arch. The samples were scanned using
      CS 9000 3D scanner with two exposure protocols: 85 kV 6.3 mA and 85 kV 10 mA.
      Voxel size and FOV were fixed at 0.100 mm and 5 cm * 3.75 cm. The presence of
      artefacts was assessed qualitatively by two calibrated observers using the CBCT
      volume and paired 2D images, and quantitatively by one trained observer, using
      ImageJ software. Wilcoxon's signed rank, Mann-Whitney, kappa and chi-square tests
      were used for qualitative analyses. Two-way anova and Tukey's tests were used for
      quantitative analyses. All analyses were conducted considering the 95% confidence
      level (alpha < 0.05). RESULTS: For the CBCT volume qualitative analysis,
      significant differences were observed between the metal alloys in the presence of
      an extra restored tooth, with higher artefact intensity for AgPd when assessing
      hypodense halos and lines (P = 0.006). Images with two restored teeth had
      significantly more hypodense and hyperdense lines (P = 0.033). When evaluating
      exposure parameters and number of restored teeth, the paired image quality
      analysis revealed significant disagreement between observers for diagnostic image
      quality (P = 0.001). Quantitative artefact analysis revealed higher artefact
      intensity for the AgPd posts in the presence of two restored teeth. CONCLUSION:
      Although the exposure parameters tested did not interfere with artefact
      intensity, post alloys with a higher atomic number and the presence of another
      metal structure in the arch increased artefact intensity and impaired the
      diagnostic quality of CBCT images.

PMID- 30107038
TI  - Ultrasound of peripheral nerves in neuralgic amyotrophy.
AB  - INTRODUCTION: Neuralgic amyotrophy (NA) can often be difficult to diagnose. Nerve
      ultrasound (US) is potentially useful, but it is operator-dependent, especially
      for small nerves. METHODS: Fifty-one consecutive patients with NA (mean duration
      16 months) and 50 control subjects underwent US of the brachial plexus and major
      nerves of the upper extremity at predefined sites. We compared cross-sectional
      areas (CSAs) of affected and unaffected sides with controls and sides within
      patients. RESULTS: The median nerve and radial nerve at the level of the upper
      arm were enlarged on the affected sides compared with controls and the unaffected
      sides of patients. Enlargement was most pronounced for affected sides vs.
      controls (median 44%, radial 67%). DISCUSSION: NA patients showed increased CSAs,
      especially in the major nerves of the upper limb, even after longer disease
      duration. This could make US a useful adjunct in diagnosing NA. Muscle Nerve,
      2018.

PMID- 30107040
TI  - Tumor Drug Penetration Measurements Could Be the Neglected Piece of the
      Personalized Cancer Treatment Puzzle.
AB  - Precision medicine aims to use patient genomic, epigenomic, specific drug dose,
      and other data to define disease patterns that may potentially lead to an
      improved treatment outcome. Personalized dosing regimens based on tumor drug
      penetration can play a critical role in this approach. State-of-the-art
      techniques to measure tumor drug penetration focus on systemic exposure, tissue
      penetration, cellular or molecular engagement, and expression of pharmacological
      activity. Using in silico methods, this information can be integrated to bridge
      the gap between the therapeutic regimen and the pharmacological link with
      clinical outcome. These methodologies are described, and challenges ahead are
      discussed. Supported by many examples, this review shows how the combination of
      these techniques provides enhanced patient-specific information on drug
      accessibility at the tumor tissue level, target binding, and downstream
      pharmacology. Our vision of how to apply tumor drug penetration measurements
      offers a roadmap for the clinical implementation of precision dosing.

PMID- 30107039
TI  - Isolated Schistosoma mansoni eggs prevent allergic airway inflammation.
AB  - Chronic helminth infection with Schistosoma (S.) mansoni protects against
      allergic airway inflammation (AAI) in mice and is associated with reduced Th2
      responses to inhaled allergens in humans, despite the presence of schistosome
      specific Th2 immunity. Schistosome eggs strongly induce type 2 immunity and allow
      to study the dynamics of Th2 versus regulatory responses in the absence of worms.
      Treatment with isolated S. mansoni eggs by i.p. injection prior to induction of
      AAI to ovalbumin (OVA)/alum led to significantly reduced AAI as assessed by less
      BAL and lung eosinophilia, less cellular influx into lung tissue, less OVA
      specific Th2 cytokines in lungs and lung-draining mediastinal lymph nodes and
      less circulating allergen-specific IgG1 and IgE antibodies. While OVA-specific
      Th2 responses were inhibited, treatment induced a strong systemic Th2 response to
      the eggs. The protective effect of S. mansoni eggs was unaltered in MUMT mice
      lacking mature (B2) B cells and unaffected by Treg cell depletion using anti-CD25
      blocking antibodies during egg treatment and allergic sensitization. Notably,
      prophylactic egg treatment resulted in a reduced influx of pro-inflammatory,
      monocyte-derived dendritic cells into lung tissue of allergic mice following
      challenge. Altogether, S. mansoni eggs can protect against the development of
      AAI, despite strong egg-specific Th2 responses.

PMID- 30107041
TI  - Energy metabolism of white adipose tissue and insulin resistance in humans.
AB  - BACKGROUND: Insulin resistance not only occurs in obesity, but also in
      lipodystrophy. Although adipose tissue mass affects metabolic fluxes and
      participates in interorgan crosstalk, the role of energy metabolism within white
      adipose tissue for insulin resistance is less clear. MATERIALS AND METHODS: A
      Medline search identified in vivo studies in humans on energy and lipid
      metabolism in subcutaneous (SAT) and visceral adipose tissue (VAT). Studies in
      adipocyte cultures and transgenic animal models were included for the better
      understanding of the link between abnormal energy metabolism in adipose tissue
      and insulin resistance. RESULTS: The current literature indicates that higher
      lipolysis and lower lipogenesis in VAT compared to SAT enhance portal delivery of
      lipid metabolites (glycerol and fatty acids) to the liver. Thus, the lower
      lipolysis and higher lipogenesis in SAT favour storage of excess lipids and allow
      for protection of insulin-sensitive tissues from lipotoxic effects. In insulin
      resistant humans, enhanced lipolysis and impaired lipogenesis in adipose tissue
      lead to release of cytokines and lipid metabolites, ultimately promoting insulin
      resistance. Adipose tissue of insulin-resistant humans also displays lower
      expression of proteins involved in mitochondrial function. In turn, this leads to
      lower availability of mitochondria-derived energy sources for lipogenesis in
      adipose tissue. CONCLUSIONS: Abnormal mitochondrial function in human white
      adipose tissue likely contributes to the secretion of lipid metabolites and
      lactate, which are linked to insulin resistance in peripheral tissues. However,
      the relevance of adipose tissue energy metabolism for the regulation of human
      insulin sensitivity remains to be further elucidated.

PMID- 30107043
TI  - The benefits of adding metformin to tamoxifen to protect the endometrium-A
      randomized placebo-controlled trial.
AB  - BACKGROUND: We investigated whether metformin prevents tamoxifen-induced
      endometrial changes and insulin resistance (IR) after a diagnosis of breast
      cancer. METHODS: This was a single-centre, randomized, double-blind, placebo
      controlled, parallel group trial. Postmenopausal women with hormone receptor
      positive breast cancer taking tamoxifen were randomly allocated to metformin 850
      mg or identical placebo, twice daily, for 52 weeks. Outcome measures included
      double endometrial thickness (ET) measured by transvaginal ultrasound, fasting
      insulin, glucose and IR estimated by the homeostasis model of assessment (HOMA
      IR). RESULTS: A total of 112 women were screened and 102 randomized. Results are
      presented as median (range). The 101 women who took at least one dose of
      medication were aged 56 (43-72) years, with 5(0.5-28) years postmenopause, and
      had taken tamoxifen for 28.9 (0-367.4) weeks. The baseline ET was 2.9 mm (1.4
      21.9) for the placebo group (n = 52) and 2.5 mm (1.3-14.8) for the metformin
      group (n = 50). At 52 weeks, the median ET was statistically significantly lower
      for the metformin (n = 36) than for the placebo group (n = 45) (2.3 mm (1.4-7.8)
      vs 3.0 (1.2-11.3); P = 0.05). 13.3% allocated to placebo had an ET greater than 4
      mm vs 5.7% for metformin (P = 0.26). There was no endometrial atypia or cancer.
      Compared with placebo, metformin resulted in significantly greater baseline
      adjusted reductions in weight (P < 0.001), waist circumference (0.03) and HOMA-IR
      (P < 0.001). CONCLUSIONS: Metformin appears to inhibit tamoxifen-induced
      endometrial changes and has favourable metabolic effects. Further research into
      the adjuvant use of metformin after breast cancer and to prevent EH and cancer is
      warranted.

PMID- 30107042
TI  - Effect of calcium citrate vs calcium carbonate on elevated parathyroid hormone
      after Roux-en-Y gastric bypass. A double-blinded, randomized trial.
AB  - OBJECTIVE: Following Roux-en-Y gastric bypass (RYGB), elevated parathyroid
      hormone (PTH) levels potentially harmful to bone health are commonly observed.
      Owing to assumed superior absorption, calcium citrate is often recommended over
      calcium carbonate following RYGB for the treatment of elevated PTH. We aimed to
      investigate the impact of either calcium carbonate or calcium citrate (1200 mg
      elementary calcium) in patients with elevated PTH levels following RYGB. DESIGN:
      Clinical, double-blinded, randomized controlled trial of a 12-week duration at a
      Danish University Hospital. PATIENTS AND MEASUREMENTS: Thirty-nine (no drop out)
      RYGB operated patients with elevated PTH levels (PTH > 6.9 pmol/L) and normal
      plasma levels of calcium and 25-hydroxyvitamin D were randomized to either
      calcium carbonate or calcium citrate (1200 mg elementary calcium/daily). We
      assessed change in PTH as the primary outcome. RESULTS: The effect of the two
      calcium formulations on change in PTH was comparable and neutral: -1.9% (calcium
      citrate) vs +0.9% (calcium carbonate), P = 0.680. Compared to the carbonate
      treated group, the following bone turnover markers decreased significantly in the
      citrate-treated group: procollagen I N-terminal propeptide (-16.6% vs -3.2%, P =
      0.021), osteocalcin (-17.2% vs -4.3%, P = 0.007) and bone-specific alkaline
      phosphatase (-5.9% vs 3.7%, P = 0.027) and remained significantly decreased after
      multivariable adjustment. CONCLUSION: Increasing the dose of calcium
      supplementation in RYGB operated patients with slightly elevated PTH levels does
      not normalize PTH levels, regardless of the type of supplement. Our results do
      not support recommending supplementation with calcium citrate over calcium
      carbonate in RYGB patients.

PMID- 30107044
TI  - The transcription and expression profile of p53N236S mutant reveals new aspects
      of gain of function for mutant p53.
AB  - Missense mutations in the p53 coding gene cause loss and gain of function. We
      have identified a hotspot mutation, p53N236S , which results in the aggressive
      progression of tumorigenesis in a knock-in mouse model. To understand the
      biological significance of the p53N236S mutation, we performed ChIP-on-chip
      combined with microarray assay to profile the regulated gene expression pattern.
      We could classify the p53N236S mutant function into six categories. Among these,
      we reveal a new aspect of gain of function, the enhancement of wild-type p53
      function, which has not been reported previously. We also show the existence of
      residual wild-type p53 function in p53N236S . Our data shed light on
      understanding the difference between this type of low-incidence hotspot p53
      mutations and classical hotspot mutations.

PMID- 30107045
TI  - The Imaginal Disc Growth Factors 2 and 3 participate in the Drosophila response
      to nematode infection.
AB  - The Drosophila imaginal disc growth factors (IDGFs) induce the proliferation of
      imaginal disc cells and terminate cell proliferation at the end of larval
      development. However, the participation of Idgf-encoding genes in other
      physiological processes of Drosophila including the immune response to infection
      is not fully understood. Here, we show the contribution of Idgf2 and Idgf3 in the
      Drosophila response to infection with Steinernema carpocapsae nematodes carrying
      or lacking their mutualistic Xenorhabdus nematophila bacteria (symbiotic or
      axenic nematodes, respectively). We find that Idgf2 and Idgf3 are upregulated in
      Drosophila larvae infected with symbiotic or axenic Steinernema and inactivation
      of Idgf2 confers a survival advantage to Drosophila larvae against axenic
      nematodes. Inactivation of Idgf2 induces the Imd and Jak/Stat pathways, whereas
      inactivation of Idgf3 induces the Imd, Toll and Jak/Stat pathways. We also show
      that inactivation of the Imd pathway receptor PGRP-LE upregulates Idgf2 against
      Steinernema nematode infection. Finally, we demonstrate that inactivation of
      Idgf3 induces the recruitment of larval haemocytes in response to Steinernema.
      Our results indicate that Idgf2 and Idgf3 might be involved in different yet
      crucial immune functions in the Drosophila antinematode immune response. Similar
      findings will promote the development of new targets for species-specific pest
      control strategies.

PMID- 30107047
TI  - Reply.

PMID- 30107046
TI  - Heritability, selection, and the response to selection in the presence of
      phenotypic measurement error: Effects, cures, and the role of repeated
      measurements.
AB  - Quantitative genetic analyses require extensive measurements of phenotypic
      traits, a task that is often not trivial, especially in wild populations. On top
      of instrumental measurement error, some traits may undergo transient (i.e.,
      nonpersistent) fluctuations that are biologically irrelevant for selection
      processes. These two sources of variability, which we denote here as measurement
      error in a broad sense, are possible causes for bias in the estimation of
      quantitative genetic parameters. We illustrate how in a continuous trait
      transient effects with a classical measurement error structure may bias estimates
      of heritability, selection gradients, and the predicted response to selection. We
      propose strategies to obtain unbiased estimates with the help of repeated
      measurements taken at an appropriate temporal scale. However, the fact that in
      quantitative genetic analyses repeated measurements are also used to isolate
      permanent environmental instead of transient effects requires that the
      information content of repeated measurements is carefully assessed. To this end,
      we propose to distinguish "short-term" from "long-term" repeats, where the former
      capture transient variability and the latter help isolate permanent effects. We
      show how the inclusion of the corresponding variance components in quantitative
      genetic models yields unbiased estimates of all quantities of interest, and we
      illustrate the application of the method to data from a Swiss snow vole
      population.

PMID- 30107049
TI  - Development and validation of the periodontal aesthetic perception scale in
      patients with periodontal problems.
AB  - AIM: The aim of this study was to develop and validate a periodontal aesthetic
      specific tool to assess aesthetic conditions perceived by patients with
      periodontal problems. MATERIALS AND METHODS: Hundred patients were interviewed
      that described the nonaesthetic gingival appearance. An item pool with 22 items
      was generated. Subsequently, expert opinion on the selected item pool was
      gathered. In accordance with expert opinions, the questionnaire was finalized by
      reducing the number of items to 7. The questionnaire tested on three patient
      groups (gingival recession group, gingival enlargement group and periodontal
      healthy group). Then, the validity and reliability of the questionnaire were
      examined. RESULTS: According to the results of the exploratory factor analysis
      (EFA), 1 item was removed from the scale. The final 6-item questionnaire was
      shown to have a two-domain structure. Cronbach's alpha for the whole scale was
      0.766. The interclass correlation coefficients (ICCs) values were between 0.98
      and 1.00, demonstrating excellent agreement. Overall, these findings indicated
      that the Periodontal Aesthetic Perception Scale (PAPS) has good reliability.
      CONCLUSION: This reliable, valid and short questionnaire specific to aesthetic
      conditions perceived by patients with periodontal problems may serve as a valued
      instrument in future clinical trials.

PMID- 30107048
TI  - Evaluation of peri-implant marginal tissues around tissue-level and bone-level
      implants in patients with a history of chronic periodontitis.
AB  - OBJECTIVE: To evaluate clinical and radiographic characteristics in peri-implant
      marginal tissues in patients with a history of chronic periodontitis,
      rehabilitated using tissue-level or bone-level implants. MATERIAL AND METHODS:
      Using a split-mouth design, 20 patients with a history of chronic periodontitis
      were selected and received two different implants, tissue-level group (n = 20)
      and the bone-level group (n = 20). Peri-implant probing depth, relative peri
      implant mucosal margin position, relative peri-implant clinical attachment level,
      peri-implant plaque index and peri-implant bleeding on probing were evaluated at
      prosthesis installation, 1, 3, 6, 12 and 24 months after implant loading.
      Radiographic marginal bone level was evaluated at implant insertion, prosthesis
      installation, 6 and 24 months after implant loading. RESULTS: The mean difference
      of peri-implant marginal bone resorption from implant installation to 24 months
      in function was 0.75 +/- 1.12 mm for the tissue-level group and 0.70 +/- 0.72 mm
      for the bone-level group. No statistically significant difference was found
      between groups at all assessment periods for clinical and radiographic peri
      implant evaluation. CONCLUSION: Under a rigid supportive therapy, both approaches
      performed likewise regarding clinical and radiographic parameters for
      rehabilitation of patients with a history of chronic periodontitis.

PMID- 30107051
TI  - Gold nanoparticles for enhanced ionization and fragmentation of biomolecules
      using LDI-MS.
AB  - New applications for gold nanoparticles (AuNPs) in laser desorption ionization
      mass spectrometry are presented here. This work expands on previous biomolecule
      studies and introduces carbohydrates, steroids, bile acids, and other small
      molecules as a focus. Broad trends in ionization are observed, and specifically
      of interest are new species that have not previously been reported from AuNPs
      (e.g., [M + Au]+ ). Interesting fragmentation effects have been observed for
      diphenhydramine, including similarity to electron impact mass spectra and
      possible radical driven reactions, providing insight into the mechanism of
      ionization when using AuNPs.

PMID- 30107050
TI  - A case of pediatric acute myeloid leukemia with t(11;16)(q23;q24) leading to a
      novel KMT2A-USP10 fusion gene.
AB  - We present a leukemia case that exhibits a chromosomal translocation
      t(11;16)(q23;q23), which results in the expression of a novel KMT2A fusion gene.
      This novel fusion, KMT2A-USP10, was found in a relapse of acute myeloid leukaemia
      M5a. USP10 belongs to a protein family that deubiquitinates a distinct set of
      target proteins, and thus, increases the steady state protein levels of its
      target subproteome. One of the USP10 targets is TP53. Wildtype TP53 is usually
      rescued from proteasomal degradation by USP10. As most KMT2A leukemias display
      wildtype p53 alleles, one might argue that the disruption of an USP10 allele can
      be classified as a pro-oncogenic event.

PMID- 30107052
TI  - Multisensory stimulation modulates perceptual and post perceptual face
      representations: Evidence from event-related potentials.
AB  - Seeing a face being touched in spatial and temporal synchrony with the own face
      produces a bias in self-recognition, whereby the other face becomes more likely
      to be perceived as the self. The present study employed event-related potentials
      to explore whether this enfacement effect reflects initial face encoding,
      enhanced distinctiveness of the enfaced face, modified self-identity
      representations, or even later processing stages that are associated with the
      emotional processing of faces. Participants were stroked in synchrony or
      asynchrony with an unfamiliar face they observed on a monitor in front of them,
      in a situation approximating a mirror image. Subsequently, event-related
      potentials were recorded during the presentation of (a) a previously
      synchronously stimulated face, (b) an asynchronously stimulated face, (c)
      observers' own face, (d) filler faces, and (e) a to-be-detected target face,
      which required a response. Observers reported a consistent enfacement illusion
      after synchronous stimulation. Importantly, the synchronously stimulated face
      elicited more prominent N170 and P200 responses than the asynchronously
      stimulated face. By contrast, similar N250 and P300 responses were observed in
      these conditions. These results suggest that enfacement modulates early neural
      correlates of face encoding and facial prototypicality, rather than identity self
      representations and associated emotional processes.

PMID- 30107054
TI  - Antibiotic prophylaxis in neutropenic children with acute leukemia: Do the
      presently available data really support this practice?
AB  - Antibiotics are frequently administered for prophylaxis of fever in neutropenic
      children with cancer. This strategy is mainly derived from adults' data, and
      various pediatric studies evidenced the effectiveness of antibiotics (eg,
      fluoroquinolones) in the prevention of febrile neutropenia. However, only two
      pediatric randomized, double-blind, placebo-controlled trials have been
      performed, with a total of 262 leukemic children enrolled, and no other one was
      ever powered for analyzing effectiveness over other infectious complications. In
      an era of increasing antibiotic resistance, the widespread use of antibiotic
      prophylaxis in neutropenic leukemic children needs to be strongly supported.

PMID- 30107053
TI  - Novel eosinophilic gene expression networks associated with IgE in two distinct
      asthma populations.
AB  - BACKGROUND: Asthma represents a significant public health burden; however, novel
      biological therapies targeting immunoglobulin E (IgE)-mediated pathways have
      widened clinical treatment options for the disease. OBJECTIVE: In this study, we
      sought to identify gene transcripts and gene networks involved in the
      determination of serum IgE levels in people with asthma that can help inform the
      development of novel therapeutic agents. METHODS: We analysed gene expression
      data from a cross-sectional study of 326 Costa Rican children with asthma, aged 6
      to 12 years, from the Genetics of Asthma in Costa Rica Study and 610 young adults
      with asthma, aged 16 to 25 years, from the Childhood Asthma Management Program
      trial. We utilized differential gene expression analysis and performed weighted
      gene coexpression network analysis on 25 060 genes, to identify gene transcripts
      and network modules associated with total IgE, adjusting for age and gender. We
      used pathway enrichment analyses to identify key biological pathways underlying
      significant modules. We compared findings that replicated between both
      populations. RESULTS: We identified 31 transcripts associated with total IgE that
      replicated between the two study cohorts. These results were notable for
      increased eosinophil-related transcripts (including IL5RA, CLC, SMPD3, CCL23 and
      CEBPE). Pathway enrichment identified the regulation of T cell tolerance as
      important in the determination of total IgE levels, supporting a key role for
      IDO1. CONCLUSIONS AND CLINICAL RELEVANCE: These results provide robust evidence
      that biologically meaningful gene expression profiles (relating to eosinophilic
      and regulatory T cell pathways in particular) associated with total IgE levels
      can be identified in individuals diagnosed with asthma during childhood. These
      profiles and their constituent genes may represent novel therapeutic targets.

PMID- 30107055
TI  - Driver mutations of young lung adenocarcinoma patients with malignant pleural
      effusion.
AB  - Young lung cancer patients have several distinct characteristics. However, there
      are limited epidemiological data of genetic abnormalities in this population. We
      conducted a prospective cohort study to delineate the various oncogenic driver
      mutations of lung adenocarcinoma in young Asian patients. We consecutively
      collected malignant pleural effusions (MPEs) from lung adenocarcinoma patients.
      RNA was extracted from MPEs for mutation analysis by reverse transcription
      polymerase chain reaction and direct sequencing. Selected gene mutations for
      testing included EGFR, HER2, BRAF, KRAS, PIK3CA, JAK2, MEK1, NRAS, and AKT2
      mutations, as well as EML4-ALK, ROS1, and RET fusions. We collected MPEs from 142
      patients aged <=50 years and 730 patients aged >50 years. Patients aged <=50
      years (91%) had a higher incidence of driver gene mutations than those aged >50
      years (84%; P = .036), especially EML4-ALK (P < .001) and ROS1 (P < .001). Among
      patients aged <=50 years, EGFR mutation was the major oncogenic driver mutation.
      The mutation rates of other genes were 18% EML4-ALK, 6% ROS1, 5% HER2, 1% RET, 1%
      BRAF, and 1% KRAS. We did not detect PIK3CA, JAK2, MEK1, NRAS, or AKT2 mutations.
      No difference in gender or smoking history was noted among those with different
      driver mutations. Patients who had a good performance status or received
      appropriate targeted therapy had longer overall survival. In conclusion, lung
      adenocarcinoma in Asian patients aged <=50 years had a higher gene mutation rate
      than in those aged >50 years, especially EML4-ALK and ROS1 fusion. Mutation
      analysis may be helpful in determining targeted therapy for the majority of these
      patients.

PMID- 30107056
TI  - Magnetization Blocking in Fe2 III Dy2 III Molecular Magnets: Ab Initio
      Calculations and EPR Spectroscopy.
AB  - The magnetism and magnetization blocking of a series of [Fe2 Dy2 (OH)2 (teaH)2
      (RC6 H4 COO)6 ] complexes was investigated, in which teaH3 =triethanolamine and
      R=meta-CN (1), para-CN (2), meta-CH3  (3), para-NO2  (4) and para-CH3  (5), by
      combining ab initio calculations and EPR measurements. The results of broken
      symmetry DFT calculations show that in all compounds the Fe-Fe exchange
      interaction is antiferromagnetic and stronger by far than the Fe-Dy and Dy-Dy
      interactions. As a result, the lowest two exchange doublets probed by EPR
      spectroscopy mostly originate from the Ising interaction of the dysprosium ions
      in all compounds. A correct quantitative description of the splitting of these
      two doublets requires, however, an explicit account of the Fe-Dy and Fe-Fe
      interactions. Due to the inversion symmetry of the complexes, the doublets under
      consideration are described by a collinear Ising exchange interaction. This
      picture is also supported by the EPR spectra, which could be simulated with
      parameters close to those extracted from the calculations. The magneto-structural
      analysis shows an increase of the antiferromagnetic Fe-Fe exchange interaction
      with increasing Fe-O-Fe angle and Fe-Fe distance. For the Dy-Fe interaction, the
      opposite tendency is observed, that is, a decrease of antiferromagnetic exchange
      coupling with increasing Dy-O-Fe angle and Dy-Fe distance. The transversal g
      factors extracted from the ab initio calculations have values in the range of
      0.01-0.2, testifying to the lack of high axiality of the ground state of the
      dysprosium ions. This explains the lack/poor single-molecule magnetic behavior of
      this series of compounds at the investigated temperatures of a few Kelvin. Due to
      a very small gap (fractions of a wavenumber) between the ground and first-excited
      exchange doublet, relaxation takes place by magnetic moment reversal at
      individual dysprosium sites in the considered temperature domain.

PMID- 30107058
TI  - A novel STRIPAK complex component mediates hyphal fusion and fruiting-body
      development in filamentous fungi.
AB  - The STRIPAK complex is involved in growth, cell fusion, development and signaling
      pathways, and thus malfunctions in the human STRIPAK complex often result in
      severe neuronal diseases and cancer. Despite the high degree of general
      conservation throughout the complex, several STRIPAK complex-associated small
      coiled-coil proteins of animals and yeasts are not conserved across species. As
      there are no data for filamentous ascomycetes, we addressed this through affinity
      purification with HA-tagged striatin ortholog PRO11 in Sordaria macrospora.
      Combining the method with liquid chromatography-mass spectrometry, we were able
      to co-purify STRIPAK complex interactor 1 (SCI1), the first STRIPAK-associated
      small coiled-coil protein in filamentous ascomycetes. Using yeast two-hybrid
      experiments, we identified SCI1 protein regions required for SCI1-PRO11
      interaction, dimerization of SCI1 and interaction with other STRIPAK components.
      Further, both proteins PRO11 and SCI1 co-localize with the nuclear basket protein
      SmPOM152 at the nuclear envelope. Expression of the gene sci1 occurs during early
      developmental stages of S. macrospora, and the protein SCI1 in combination with
      PRO11 is required for cell fusion, vegetative growth and sexual development. The
      results of the present study will help to understand the underlying molecular
      mechanisms of STRIPAK signaling and function in cellular development and diseases
      in higher eukaryotes.

PMID- 30107057
TI  - NOx in exhaled breath condensate is related to allergic sensitization in young
      and middle-aged adults.
AB  - BACKGROUND: Asthma and allergic diseases are heterogeneous. Measurement of
      biomarkers in exhaled breath condensate (EBC) may help to discriminate between
      different phenotypes and may assist with clinical prognostication. OBJECTIVES: We
      aimed to assess associations between total nitric oxide products (NOx ) in EBC
      and different allergic phenotypes and lung function in young and middle-aged
      adults. METHODS: Cross-sectional analyses were nested within two Australian
      longitudinal studies, the Melbourne Atopy Cohort Study (MACS, mean age 17.8
      years) and the Tasmanian Longitudinal Health Study (TAHS, mean age 49.4 years).
      Levels of EBC NOx were determined by Griess-reaction fluorescent method.
      Associations were assessed between EBC NOx and different allergic phenotypes,
      lung function and airway reactivity. RESULTS: Atopy, with or without asthma or
      rhinitis, was associated with increased EBC NOx levels particularly in
      individuals with poly-aero-sensitization. These findings were generally
      consistent across the two age groups. In the older cohort, use of ICS in the
      previous 12 months masked the association between sensitization and EBC NOx (OR =
      0.64, 95% CI = 0.21-1.96, p for interaction = 0.05). CONCLUSIONS AND CLINICAL
      RELEVANCE: In these population-based samples, EBC NOx was most strongly
      associated with atopic sensitization, rather than either current asthma or
      rhinitis, possibly indicating underlying increased airway inflammation associated
      with atopy. Therefore, EBC NOx could be a key predictor of atopy in both young
      and middle-aged adults, regardless of the presence of concomitant asthma or
      rhinitis.

PMID- 30107059
TI  - Endotypes of severe allergic asthma patients who clinically benefit from anti-IgE
      therapy.
AB  - BACKGROUND: Omalizumab, a recombinant monoclonal anti-IgE antibody, was developed
      for the treatment of severe allergic asthma. Not all these patients respond to
      omalizumab. OBJECTIVE: This study aimed to evaluate whether the proinflammatory
      cytokine profiles in the severe allergic asthma patients were different between
      who responded and nonresponded to omalizumab therapy. METHODS: A prospective
      study was conducted to examine type 2 cytokines and epithelium-derived cytokines
      in the bronchial tissues by immunohistochemistry, Western blot and PCR analysis
      among patients with severe allergic asthma before and after omalizumab therapy.
      RESULTS: Fourteen of 23 patients with unstable severe allergic asthma improved
      their asthma control after 4 months of omalizumab treatment (Responders), while
      nine failed to improve (Non-Responders). Most of Responders were type 2-high
      endotype (12/14) with upregulated expression of IL-33, IL-25 and TSLP in their
      bronchial tissues, while most of Non-Responders were type 2-low endotype (8/9).
      Repeated bronchoscopic biopsy was done in nine responders after omalizumab
      treatment and showed a decline in IL-13, IL-33, IL-25 and TSLP expression in the
      bronchial tissues. Among 14 Responders who continued omalizuamb treatments to a
      total 12 months, six patients achieved a well control of asthma (ACT >= 23),
      while eight patients required additional treatment for asthma symptoms and had
      more rhinosinusitis comorbidities and a mixed eosinophilic and neutrophilic
      inflammation in their bronchial tissues. CONCLUSION: Most of the severe allergic
      asthma patients who benefited from omalizumab treatment were IL-33, IL-25 and
      TSLP aggravated type 2-high endotype. Rhinosinusitis or with a mixed eosinophilic
      and neutrophilic airway inflammation should be evaluated in patients who
      partially responded to omalizumab treatment.

PMID- 30107060
TI  - How to estimate kinship.
AB  - The concept of kinship permeates many domains of fundamental and applied biology
      ranging from social evolution to conservation science to quantitative and human
      genetics. Until recently, pedigrees were the gold standard to infer kinship, but
      the advent of next-generation sequencing and the availability of dense genetic
      markers in many species make it a good time to (re)evaluate the usefulness of
      genetic markers in this context. Using three published data sets where both
      pedigrees and markers are available, we evaluate two common and a new genetic
      estimator of kinship. We show discrepancies between pedigree values and marker
      estimates of kinship and explore via simulations the possible reasons for these.
      We find these discrepancies are attributable to two main sources: pedigree errors
      and heterogeneity in the origin of founders. We also show that our new marker
      based kinship estimator has very good statistical properties and behaviour and is
      particularly well suited for situations where the source population is of small
      size, as will often be the case in conservation biology, and where high levels of
      kinship are expected, as is typical in social evolution studies.

PMID- 30107062
TI  - Beneficial effects of bilateral subthalamic stimulation on alexithymia in
      Parkinson's disease.
AB  - BACKGROUND AND PURPOSE: Subthalamic nucleus (STN) deep brain stimulation (DBS)
      improves quality of life (QoL) and motor and non-motor symptoms in advanced
      Parkinson's disease (PD). However, its effect on alexithymia and its relationship
      to other neuropsychiatric symptoms and QoL in PD is unclear. METHODS: In this
      prospective, observational study of 39 patients with PD undergoing STN-DBS, we
      examined the Parkinson's Disease Questionnaire-8 (PDQ-8), 20-item Toronto
      Alexithymia Scale (TAS-20), Hospital Anxiety and Depression Scale (HADS), Self
      Report Manic Inventory (SRMI), Apathy Evaluation Scale (AES), Unified Parkinson's
      Disease Rating Scale (UPDRS) activities of daily living, UPDRS motor examination
      and UPDRS complications (UPDRS-II/-III/-IV) and levodopa-equivalent daily dose
      (LEDD) pre-operatively and at 5-month follow-up. Outcome changes were tested with
      Wilcoxon signed-rank or paired t-test when parametric tests were applicable and
      corrected for multiple comparisons. The relationship between outcome changes was
      explored with bivariate correlations. Additionally, partial correlations between
      PDQ-8 and TAS-20 were computed controlling for HADS, SRMI and AES change scores.
      Predictor analyses for PDQ-8 improvement were calculated for all baseline
      parameters. RESULTS: The baseline prevalence of alexithymia was 17.9%. We
      observed significant beneficial effects of STN-DBS on PDQ-8, TAS-20, HADS, UPDRS
      II, -III and -IV scores and significant LEDD reduction. The correlation between
      TAS-20 and PDQ-8 improvements remained significant after controlling for all
      other aforementioned outcomes. Predictor analyses for PDQ-8 improvement were
      significant for PDQ-8 and TAS-20. CONCLUSIONS: This is the first report of
      beneficial effects of STN-DBS on alexithymia. Alexithymia was significantly
      associated with QoL outcome independent of anxiety, depression, mania and apathy.
      Our study highlights the importance of alexithymia for holistic assessments of
      DBS outcomes.

PMID- 30107063
TI  - Relative abundances of novel cyclic prodelphinidins in wine depending on the
      grape variety.
AB  - The identification of cyclic B-type procyanidins in grape and wine was recently
      disclosed. Some of these were also found in berries of totally different vegetal
      species (eg, Vaccinium sp.). However, presence of a wider class of these cyclic
      condensed tannin compounds with variably substituted monomers has never been
      addressed so far. Here, an extended list of oligomeric cyclic proanthocyanidins
      (PAC) bearing variable substitution patterns on the main flavan-3-ol unit has
      been searched in wines. Nearly 7600 theoretical structures were calculated and
      searched in red and white wine samples made from different grape varieties.
      Moreover, a hydrogen/deuterium exchange approach (already applied to a cyclic
      tetrameric procyanidin) coupled to high-resolution mass spectrometry was applied
      to confirm their cyclic B-type structure rather than a non cyclic A-type
      structure, otherwise isomeric and undistinguishable by LC-MS alone. The main
      group of novel cyclic PAC observed is shown to contain (epi)gallocatechin beside
      (epi)catechin as the constituent monomers.

PMID- 30107061
TI  - Prefrontal cortex modulates firing pattern in the nucleus reuniens of the midline
      thalamus via distinct corticothalamic pathways.
AB  - The thalamus has long been recognized for its role in relaying sensory
      information from the periphery, a function accomplished by its "first-order"
      nuclei. However, a second category of thalamic nuclei, termed "higher-order"
      nuclei, have been shown instead to mediate communication between cortical areas.
      The nucleus reuniens of the midline thalamus (RE) is a higher-order nucleus known
      to act as a conduit of reciprocal communication between the medial prefrontal
      cortex (mPFC) and hippocampus. While anatomical and behavioural studies of RE are
      numerous, circuit-based electrophysiological studies, particularly those
      examining the impact of cortical input and the thalamic reticular nucleus (TRN)
      on RE neuron firing, are sparse. To characterize RE neuron firing properties and
      dissect the circuit dynamics of the infralimbic subdivision of the mPFC (ilPFC),
      the TRN and RE, we used in vivo, extracellular, single-unit recordings in male
      Sprague Dawley rats and manipulated neural activity using targeted
      pharmacological manipulations, electrical stimulation and a projection-specific
      implementation of designer receptors exclusively activated by designer drugs
      (DREADDs). We show that ilPFC inhibition reduces multiple burst firing parameters
      in RE, whereas ilPFC stimulation drives burst firing and dampens tonic firing. In
      addition, TRN inhibition reduces the number of spontaneously active neurons in
      RE. Finally, inhibition of ilPFC terminals in RE selectively enhances a subset of
      burst firing parameters. These findings demonstrate that ilPFC input, both via
      direct projections and via the TRN, can modulate RE neuron firing pattern in
      nuanced and complex ways. They also highlight the ilPFC-TRN-RE circuit as a
      likely critical component of prefrontal-hippocampal interactions.

PMID- 30107064
TI  - Quantitative host resistance drives the evolution of increased virulence in an
      emerging pathogen.
AB  - Emergent infectious diseases can have a devastating impact on host populations.
      The high selective pressures on both the hosts and the pathogens frequently lead
      to rapid adaptations not only in pathogen virulence but also host resistance
      following an initial outbreak. However, it is often unclear whether hosts will
      evolve to avoid infection-associated fitness costs by preventing the
      establishment of infection (here referred to as qualitative resistance) or by
      limiting its deleterious effects through immune functioning (here referred to as
      quantitative resistance). Equally, the evolutionary repercussions these different
      resistance mechanisms have for the pathogen are often unknown. Here, we
      investigate the co-evolutionary dynamics of pathogen virulence and host
      resistance following the epizootic outbreak of the highly pathogenic bacterium
      Mycoplasma gallisepticum in North American house finches (Haemorhous mexicanus).
      Using an evolutionary modelling approach and with a specific emphasis on the
      evolved resistance trait, we demonstrate that the rapid increase in the frequency
      of resistant birds following the outbreak is indicative of strong selection
      pressure to reduce infection-associated mortality. This, in turn, created the
      ecological conditions that selected for increased bacterial virulence. Our
      results thus suggest that quantitative host resistance was the key factor
      underlying the evolutionary interactions in this natural host-pathogen system.

PMID- 30107067
TI  - Probe-based confocal laser endomicroscopy of the gastric mucosa with curcumin
      dripping.

PMID- 30107066
TI  - Constitutive overexpression of TNF in BPSM1 mice causes iBALT and bone marrow
      nodular lymphocytic hyperplasia.
AB  - BPSM1 (Bone phenotype spontaneous mutant 1) mice develop severe polyarthritis and
      heart valve disease as a result of a spontaneous mutation in the Tnf gene. In
      these mice, the insertion of a retrotransposon in the 3' untranslated region of
      Tnf causes a large increase in the expression of the cytokine. We have found that
      these mice also develop inducible bronchus-associated lymphoid tissue (iBALT), as
      well as nodular lymphoid hyperplasia (NLH) in the bone marrow. Loss of TNFR1
      prevents the development of both types of follicles, but deficiency of TNFR1 in
      the hematopoietic compartment only prevents the iBALT and not the NLH phenotype.
      We show that the development of arthritis and heart valve disease does not depend
      on the presence of the tertiary lymphoid tissues. Interestingly, while loss of IL
      17 or IL-23 limits iBALT and NLH development to some extent, it has no effect on
      polyarthritis or heart valve disease in BPSM1 mice.

PMID- 30107065
TI  - Identification of a novel post-insertion step in the assembly of a bacterial
      outer membrane protein.
AB  - Although the barrel assembly machinery (Bam) complex has been shown to facilitate
      the insertion of beta barrel proteins into the bacterial outer membrane (OM), the
      stage at which beta barrels fold is unknown. Here, we describe insights into beta
      barrel assembly that emerged from an analysis of a member of the autotransporter
      family of OM proteins (EspP) in Escherichia coli. EspP contains an extracellular
      'passenger' domain that is translocated across the OM and then released from the
      covalently linked beta barrel domain in an intra-barrel cleavage reaction. We
      found that the mutation of an unusual lipid-exposed lysine residue impairs a
      previously unidentified late folding step that follows both the membrane
      insertion of the beta barrel domain and the secretion of the passenger domain but
      that precedes proteolytic maturation. Our results demonstrate that beta barrel
      assembly can be completed at a post-insertion stage and raise the possibility
      that interactions with membrane lipids can promote folding in vivo. Furthermore,
      by showing that the passenger domain is secreted before the beta barrel domain is
      fully assembled, our results also provide evidence against the long-standing
      hypothesis that autotransporters are autonomous protein secretion systems.

PMID- 30107068
TI  - Patient's perception: shorter and more severe prodromal phase in GBA-associated
      PD.
AB  - BACKGROUND: Prevalence and time of occurrence of prodromal symptoms of
      Parkinson's disease (PD) in relation to the onset of classical motor
      manifestation varies between patients. Possible modifying factors might be
      different genetic architectures predisposing to varying burden of manifestations.
      OBJECTIVES: To characterize the prodromal phase in PD patients with heterozygous
      mutations in the GBA gene compared to PD patients without GBA mutation. METHODS:
      In a retrospective design, 151 participants [47 PD patients carrying a GBA
      mutation (PDGBA ), 52 idiopathic PD patients (PDidiopathic ), 52 healthy elderly
      (CON)] underwent a validated structured interview designed to assess prevalence
      and time of occurrence of prodromal symptoms. RESULTS: PDGBA showed a higher
      prevalence of prodromal symptoms and almost simultaneous occurrence of non-motor
      and early motor symptoms shortly before PD diagnosis whereas PDidiopathic
      reported a longer prodromal phase starting with non-motor symptoms. CONCLUSION:
      The short and severe prodromal phase in PDGBA might call for shorter assessment
      intervals in yet premanifest GBA mutation carriers.

PMID- 30107069
TI  - Estimated burden of serious human fungal diseases in Turkey.
AB  - The current number of fungal infections occurring each year in Turkey is unknown.
      We estimated the burden of serious human fungal diseases based on the population
      at risk, existing epidemiological data from 1920 to 2017 and modelling previously
      described by the LIFE program (http://www.LIFE-worldwide.org). Among the
      population of Turkey (80.8 million in 2017), approximately 1 785 811 (2.21%)
      people are estimated to suffer from a serious fungal infection each year. The
      model used predicts high prevalences of allergic fungal rhinosinusitis episodes
      (312 994 cases) (392/100 000), of severe asthma with fungal sensitisation (42 989
      cases) (53.20 cases/100 000 adults per year), of allergic bronchopulmonary
      aspergillosis (32 594 cases) (40.33/100 000), of fungal keratitis (26 671 cases)
      (33/100 000) and of chronic pulmonary aspergillosis (5890 cases) (7.29/100 000).
      The estimated annual incidence for invasive aspergillosis is lower (3911 cases)
      (4.84/100 000 annually). Among about 22.5 million women aged 15-50 years,
      recurrent vulvovaginal candidiasis is estimated to occur in 1 350 371 (3342/100
      000) females. The burden of three superficial fungal infections was also
      estimated: tinea pedis (1.79 million), tinea capitis (43 900) and onychomycosis
      (1.73 million). Given that the modelling estimates reported in the current study
      might be substantially under- or overestimated, formal epidemiological and
      comprehensive surveillance studies are required to validate or modify these
      estimates.

PMID- 30107071
TI  - In vitro detection of Candida and Aspergillus antigen in parenteral nutrition and
      fixed combinations of piperacillin-tazobactam.
AB  - BACKGROUND: Screening for Aspergillus (Asp-AG) and Candida antigen (Ca-AG) with
      immunoassays is established for stem cell recipients at high risk for invasive
      fungal infections (IFI). While parenteral nutrition (PN) will be applied in case
      of complications leading to insufficient alimentation, piperacillin-tazobactam
      (TZP) is started at the onset of febrile neutropenia. OBJECTIVES: The aim of this
      study was to investigate drug-laboratory interactions between PN and TZP and both
      immunoassays which could affect the specificity of the assays and lead to the
      false assumption of an IFI. METHODS: Batches of TZP and PN were tested with both
      assays in vitro. In total, 380 samples of 83 batches were analysed. RESULTS: None
      of the examined preparations were tested positive with Asp-AG assay. Measurable
      amounts of Ca-AG were detected in a lipid emulsion, two different trace element
      supplements, a fat-soluble vitamin preparation and all tested brands of TZP.
      CONCLUSIONS: We conclude that false positivity of Asp-AG assay due to TZP and PN
      does not occur. Cross reactions with Ca-AG assay have been detected in some
      preparations. The in vivo relevance of Ca-AG positivity has to be reviewed in
      further studies considering an effect of dilution. Physicians should be aware of
      a possible cross reaction with Ca-AG assays which could lead to false-positive
      results.

PMID- 30107070
TI  - Delivering problem-solving therapy to family caregivers of people with cancer: A
      feasibility study in outpatient palliative care.
AB  - OBJECTIVE: In response to the well-documented need for evidence-based cancer
      caregiver support, we examined the feasibility of problem-solving therapy for
      family caregivers of cancer patients receiving outpatient palliative care and
      investigated the impact of problem-solving therapy on family caregivers' anxiety,
      depression, and quality of life. METHODS: We conducted a feasibility study of a
      structured problem-solving therapy intervention delivered to family caregivers of
      cancer patients receiving outpatient palliative care from an academic health
      center in the Midwestern United States. Participants (N = 83) were randomly
      assigned to receive usual care or usual care plus a problem-solving therapy
      intervention, which was delivered over three sessions via web-based
      videoconferencing or telephone. Descriptive statistics were used to determine
      feasibility relative to recruitment, retention, and fidelity to core intervention
      components. Outcome data were analyzed using ordinary least squares multiple
      regression. RESULTS: Problem-solving therapy for family caregivers of patients
      with cancer was found to be highly feasible in the outpatient palliative care
      setting. Caregivers who received problem-solving therapy reported less anxiety
      than those who received only usual care (P = 0.03). No statistically significant
      differences were observed for caregiver depression (P = 0.07) or quality of life
      (P = 0.06). CONCLUSIONS: Problem-solving therapy is a feasible and promising
      approach to reducing cancer family caregivers' anxiety in the outpatient
      palliative care setting. Further testing in multiple sites is recommended.

PMID- 30107072
TI  - Serum copper and zinc levels and the risk of oral cancer: A new insight based on
      large-scale case-control study.
AB  - OBJECTIVE: Limited evidence exists on the roles of serum copper (Cu) and zinc
      (Zn) in oral cancer risk. We aimed to preliminarily explore the association
      between serum Cu and Zn levels and oral cancer risk with relatively large-scale
      samples. METHODS: Serum Cu and Zn levels of 344 oral cancer patients and 1,122
      matched healthy controls in this case-control study were measured by inductively
      coupled plasma mass spectrometry (ICP-MS). RESULTS: Restricted cubic spline
      revealed the U-shaped relationship between serum Cu or Zn levels and the risk of
      oral cancer. Serum deficient or elevated levels of Cu were significantly
      associated with the risk of oral cancer: The ORs were 1.38 (95% CI: 1.01-1.89)
      and 2.82 (95% CI: 1.60-4.98), respectively. The positive association of serum low
      or high levels of Zn with oral cancer risk was also observed: The ORs were 2.72
      (95% CI: 1.60-4.62) and 12.41 (95% CI: 9.09-16.93), respectively. Additionally,
      there were multiplicative interactions between the aforementioned trace elements
      and smoking. CONCLUSIONS: This preliminary study suggests that both serum excess
      and deficient levels of Cu or Zn were significant correlation with oral cancer
      risk, which may provide a new insight on the roles of serum Cu and Zn in oral
      cancer.

PMID- 30107073
TI  - Microbiological findings in bronchoalveolar lavage fluid from lung transplant
      patients in Sweden.
AB  - BACKGROUND: Lung transplant patients experience a high risk of airway infections
      and microbial colonization of the lung due to constant exposure to the
      environment through inhaled microorganisms, denervation, reduced ciliary
      transport, and decreased cough. METHODS: In this nationwide prospective study on
      Swedish lung transplant patients, we evaluated the microbiological panorama of
      bacteria, fungi, and virus found in bronchoalveolar lavage fluid (BALF) obtained
      the first year after lung transplantation (LTx). Differences in microbiological
      findings depending of concomitant signs of infection and background factors were
      assessed. RESULTS: A total of 470 bronchoscopies from 126 patients were
      evaluated. Sixty-two percent (n = 293) of BALF samples had positive
      microbiological finding(s). Forty-six percent (n = 217) had bacterial growth, 29%
      (n = 137) fungal growth, and 9% (n = 43) were positive in viral PCR. In 38% of
      BALF samples (n = 181), a single microbe was found, whereas a combination of
      bacteria, fungi or virus was found in 24% (n = 112) of bronchoscopies. The most
      common microbiological findings were Candida albicans, Pseudomonas aeruginosa and
      coagulase negative Staphylococcus (in 42 (33%), 36 (29%), and 25 (20%) patients,
      respectively). Microbiological findings were similar in BALF from patients with
      and without signs of lung infection and the frequency of multidrug resistant
      (MDR) bacteria was low. No significant association was found between background
      factors and time to first lung infection. CONCLUSION: This study gives important
      epidemiologic insights and reinforces that microbiological findings have to be
      evaluated in the light of clinical symptoms and endobronchial appearance in the
      assessment of lung infections in lung transplant patients.

PMID- 30107074
TI  - 3D Porous Tin Created by Tuning the Redox Potential Acts as an Advanced Electrode
      for Sodium-Ion Batteries.
AB  - Sodium-ion batteries (SIBs) have attracted significant research interest for
      large-scale electric energy storage. However, anodes with good rate capability
      and long cycle life are still lacking. Here, a three-dimensional (3D) porous Sn
      on Cu foil (Sn/Cu) is prepared by tuning the redox potential of Cu+ /Cu with a
      ligand of thiourea to trigger the replacement reaction between Cu and Sn2+ . The
      as-synthesized Sn/Cu is used as an integrated porous electrode and can be
      directly applied as an advanced freestanding electrode for SIBs. Such a unique
      structure can efficiently relieve the strain caused by sodiation/desodiation and
      benefit penetration of the electrolyte and diffusion of Na+ . This is a merit of
      its large reversible capacity of about 700 mAh g-1 at 2500 mA g-1 for 400 cycles.
      A full battery of Sn/Cu//Na3 (VO0.5 )2 (PO4 )3 F2 is constructed, which presents
      a high energy density of 311.7 Wh kg-1 and long lifespan of 200 cycles. This
      facile synthesis strategy and good electrochemical performance will encourage
      more investigations into structure design of functional materials.

PMID- 30107075
TI  - Late post-kidney transplant Strongyloides hyperinfection syndrome.
AB  - Disseminated strongyloidiasis is a potentially life-threatening infection in
      organ transplant recipients that typically occurs within the first 6 months of
      transplantation. We discuss a patient from the Appalachia region of Virginia who
      appeared to acquire Strongyloides stercoralis domestically years after kidney
      transplantation and then develop disseminated strongyloidiasis.

PMID- 30107077
TI  - Beyond Friedel and Crafts: Innate Alkylation of C-H Bonds in Arenes.
AB  - Alkylated arenes are ubiquitous molecules and building blocks commonly utilized
      in most areas of science where there is a need for small organic molecules.
      Despite its apparent simplicity, the regioselective alkylation of arenes is still
      a challenging transformation in a lot of cases. Classical methods for the
      introduction of alkyl groups on arenes, which include the venerable Friedel
      Crafts reaction, radical additions, metallation or pre-functionalization of the
      arene, as well as alternatives such as the directed alkylation of C-H bonds,
      still suffer from severe limitations in terms of scope, efficiency and
      selectivity. This can be addressed by exploiting the innate reactivity of some
      (hetero)arenes, in which electronic and steric properties, governed (or not) by
      the presence of one (or multiple) heteroatom(s) ensure high levels of
      regioselectivity. These innate alkylations of C-H bonds in (hetero)arenes will be
      overviewed, in a comprehensive manner, in this review article.

PMID- 30107076
TI  - DELAYED HEADING DATE1 interacts with OsHAP5C/D, delays flowering time and
      enhances yield in rice.
AB  - Heading date is an important agronomic trait affecting crop yield. The GRAS
      protein family is a plant-specific super family extensively involved in plant
      growth and signal transduction. However, GRAS proteins are rarely reported have a
      role in regulating rice heading date. Here, we report a GRAS protein DHD1
      (Delayed Heading Date1) delays heading and enhances yield in rice. Biochemical
      assays showed DHD1 physically interacts with OsHAP5C/D both in vitro and in vivo.
      DHD1 and OsHAP5C/D located in the nucleus and showed that rhythmic expression.
      Both DHD1 and OsHAP5C/D affect heading date by regulating expression of Ehd1. We
      propose that DHD1 interacts with OsHAP5C/D to delay heading date by inhibiting
      expression of Ehd1.

PMID- 30107078
TI  - Histological picture of antibody-mediated rejection without donor-specific anti
      HLA antibodies: Clinical presentation and implications for outcome.
AB  - In this cohort study (n = 935 transplantations), we investigated the phenotype
      and risk of graft failure in patients with histological criteria for antibody
      mediated rejection (ABMR) in the absence of circulating donor-specific anti-human
      leukocyte antigen (HLA) antibodies (DSA), and compared this to patients with
      definite ABMR and HLA-DSA-positivity. The histological picture did not differ
      between HLA-DSA-positive (n = 85) and HLA-DSA-negative (n = 123) cases of ABMR
      histology, apart from increased complement split product 4d (C4d) deposition in
      the peritubular capillaries in HLA-DSA-positive cases. Histology of ABMR without
      HLA-DSA was more transient than DSA-positive ABMR, and patients with ABMR
      histology without HLA-DSA had graft survival superior to that of HLA-DSA-positive
      patients, independent of concomitant T cell-mediated rejection (38.2%) or
      borderline changes (17.9%). Multivariate analysis showed that the risk of graft
      failure was not higher in patients with histological picture of ABMR (ABMRh ) in
      the absence of HLA-DSA, compared to patients without ABMRh . Despite an
      association between C4d deposition and HLA-DSA-positivity, using C4d deposition
      as alternative for the DSA criterion in the diagnosis of ABMR, as proposed in
      Banff 2017, did not contribute to the prognosis of graft function and graft
      failure. We concluded that biopsies with ABMRh but without detectable HLA-DSA
      represent a distinct, often transient phenotype with superior allograft survival.

PMID- 30107079
TI  - Influence of custom-made and stock mouthguard thickness on biomechanical response
      to a simulated impact.
AB  - BACKGROUND/AIMS: Mouthguards (MGs) are devices that can reduce the risks of
      facial trauma. However, the large variety of MG types and thicknesses raises the
      question of which type is the most effective and beneficial for the athletes. The
      aim of this study was to evaluate stress distribution in the skull, teeth, and
      jaws as a consequence of a direct impact. MATERIAL AND METHODS: Using modeling
      software, a human skull was modeled and a human jaw was created with all teeth
      inserted into the respective alveolus. The models were divided according to the
      MG type (custom-made or stock) and thickness (1, 2, and 4 mm). Two models without
      MG were evaluated with and without teeth contact. The geometries were exported to
      analysis software and the materials were considered ideal. Fixation occurred at
      the base of the foramen magnum. The load (500 N) was applied on the canine tooth
      with a ball. Maximum principal (MPa) and Von-Mises results were obtained.
      RESULTS: Without any protection, the generated tensile stress was of greater
      magnitude causing more damage in the absence of teeth contact. The presence of a
      MG significantly reduced the generated stress in all structures, and the
      customized/individualized type was more efficient than stock MGs. CONCLUSIONS: In
      extreme situations when it is impossible to use a MG, keeping the teeth in
      maximum intercuspal position is less harmful. Despite this, the use of any MG is
      beneficial and assists in dampening the generated stress. The thicker the device,
      the greater the capacity for decreasing the damage in all structures. The use of
      individual protectors for each patient is even more beneficial for preventing
      trauma during at-risk activities of impact.

PMID- 30107080
TI  - Flow cytometric detection of most proteins in the cell surface proteome is
      unaffected by trypsin treatment.
AB  - Flow cytometry is often performed on adherent cells or solid tissues that have
      been released from their growth substrate or disaggregated by enzymatic
      digestion. Although detection of strongly expressed cell surface proteins
      following such procedures indicates that many survive treatment with proteolytic
      enzymes, applications such as cell surface proteomics involve assessment of the
      expression of more than 200 proteins and it is important to know how to interpret
      negative results. To address this problem, we performed flow cytometry-based cell
      surface proteomic analysis on two non-adherent cell lines, THP1 and K562, after
      mock and authentic trypsin treatment, according to a widely used protocol to
      remove adherent cells (0.25% trypsin, 2.21 mM EDTA, 37 degrees C, 5 min). In a
      single screening experiment, we examined the effect of treatment on mean
      fluorescence intensity and on the percent of positive cells and determined the
      false negative rate. Of 164 determinations that were >=20% positive after mock
      treatment, 13 (7.9%) were <20% positive after trypsin treatment. Four proteins
      were chosen for time-course studies (performed in triplicate), confirming initial
      sensitivity results but revealing significant variability in the magnitude of the
      trypsin effect. When trypsin sensitivity of individual proteins was examined as a
      function of the number of predicted high probability extracellular trypsin
      cleavage sites, we found that the markers that yielded false negatives all had
      high numbers of sites (>30), but even so, the majority of proteins with high
      numbers of trypsin sites could still be detected after mild trypsin treatment. We
      conclude that the great majority of cell surface proteins can be detected after
      mild trypsin treatment, but that negative results should not be over-interpreted,
      due to the possibility of false negatives.

PMID- 30107081
TI  - How Haptics and Drawing Enhance the Learning of Anatomy.
AB  - Students' engagement with two-dimensional (2D) representations as opposed to
      three-dimensional (3D) representations of anatomy such as in dissection, is
      significant in terms of the depth of their comprehension. This qualitative study
      aimed to understand how students learned anatomy using observational and drawing
      activities that included touch, called haptics. Five volunteer second year
      medical students at the University of Cape Town participated in a six-day
      educational intervention in which a novel "haptico-visual observation and
      drawing" (HVOD) method was employed. Data were collected through individual
      interviews as well as a focus group discussion. The HVOD method was successfully
      applied by all the participants, who reported an improvement of their cognitive
      understanding and memorization of the 3D form of the anatomical part. All the
      five participants described the development of a "mental picture" of the object
      as being central to "deep learning." The use of the haptic senses coupled with
      the simultaneous act of drawing enrolled sources of information that were
      reported by the participants to have enabled better memorization. We postulate
      that the more sources of information about an object, the greater degree of
      complexity could be appreciated, and therefore the more clearly it could be
      captured and memorized. The inclusion of haptics has implications for cadaveric
      dissection versus non-cadaveric forms of learning. This study was limited by its
      sample size as well as the bias and position of the researchers, but the sample
      of five produced a sufficient amount of data to generate a conceptual model and
      hypothesis.

PMID- 30107082
TI  - The ParsortixTM Cell Separation System-A versatile liquid biopsy platform.
AB  - Cancer cells from solid tumors can enter the circulatory system and survive to
      subsequently form distant metastases. The CellSearch(r) system (Menarini-Silicon
      Biosystems, Huntingdon Valley, PA) was the first, FDA-cleared system that
      provided a reliable tool for the investigation of circulating tumor cells (CTCs),
      which have been shown to be strongly associated with poor survival and therapy
      failure. Since that time, a number of new technologies have been introduced to
      improve CTC detection and/or isolation for further characterization. The
      continued and growing interest in the "liquid biopsy" field has spurred the
      development of numerous different CTC technologies. However, selecting the most
      appropriate CTC platform for individual applications can be challenging. No
      consensus has yet been reached in the community regarding which liquid biopsy
      technology is optimal. Here, we introduce the ParsortixTM Cell Separation System
      (ANGLE North America, Inc., King of Prussia, PA), a microfluidic based technology
      that captures rare cells based on size and deformability, offers reproducibly
      high capture efficiency, and produces highly enriched, viable (viability
      dependent on preservative used) CTCs that are amenable to a multitude of
      downstream analyses, including the isolation and interrogation of single cells.

PMID- 30107083
TI  - Oral microbiome activity in children with autism spectrum disorder.
AB  - Autism spectrum disorder (ASD) is associated with several oropharyngeal
      abnormalities, including buccal sensory sensitivity, taste and texture aversions,
      speech apraxia, and salivary transcriptome alterations. Furthermore, the
      oropharynx represents the sole entry point to the gastrointestinal (GI) tract. GI
      disturbances and alterations in the GI microbiome are established features of
      ASD, and may impact behavior through the "microbial-gut-brain axis." Most studies
      of the ASD microbiome have used fecal samples. Here, we identified changes in the
      salivary microbiome of children aged 2-6 years across three developmental
      profiles: ASD (n = 180), nonautistic developmental delay (DD; n = 60), and
      typically developing (TD; n = 106) children. After RNA extraction and shotgun
      sequencing, actively transcribing taxa were quantified and tested for differences
      between groups and within ASD endophenotypes. A total of 12 taxa were altered
      between the developmental groups and 28 taxa were identified that distinguished
      ASD patients with and without GI disturbance, providing further evidence for the
      role of the gut-brain axis in ASD. Group classification accuracy was visualized
      with receiver operating characteristic curves and validated using a 50/50 hold
      out procedure. Five microbial ratios distinguished ASD from TD participants
      (79.5% accuracy), three distinguished ASD from DD (76.5%), and three
      distinguished ASD children with/without GI disturbance (85.7%). Taxonomic
      pathways were assessed using the Kyoto Encyclopedia of Genes and Genomes
      microbial database and compared with one-way analysis of variance, revealing
      significant differences within energy metabolism and lysine degradation.
      Together, these results indicate that GI microbiome disruption in ASD extends to
      the oropharynx, and suggests oral microbiome profiling as a potential tool to
      evaluate ASD status. Autism Res 2018, 11: 1286-1299. (c) 2018 International
      Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Previous
      research suggests that the bacteria living in the human gut may influence
      autistic behavior. This study examined genetic activity of microbes living in the
      mouth of over 300 children. The microbes with differences in children with autism
      were involved in energy processing and showed potential for identifying autism
      status.

PMID- 30107085
TI  - Column selection approach for related substances determination of progesterone by
      high-performance liquid chromatography.
AB  - In this study, HPLC-MS/MS with triple-quadrupole tandem mass spectrometer was
      used to analyze the base-catalyzed thermal degradation derivative of progesterone
      in Chinese Pharmacopoeia. The full-scan spectrometry revealed that the
      degradation product was an isomer of progesterone, it was proposed as impurity M
      ((17alpha)-pregn-4-ene-3,20-dione) in European Pharmacopoeia, and both the
      derivative and progesterone were neutral molecules. Four kinds of chromatographic
      column characterization databases including PQRI database using Snyder/Dolan
      method, the USP chromatographic column database using the SRM 870 tests, the
      Tanaka/Euerby approach within the ACD program, and the Hoogmartens approach were
      compared. Combing the principles of column characterization databases with the
      system requirement of progesterone-related substances testing, a suitable PQRI
      based method was finally set up for progesterone-related substances detecting.
      Our results indicated that PQRI system of Snyder/Dolan method was the most
      suitable system for related substances detection of progesterone.

PMID- 30107084
TI  - The autism spectrum phenotype in ADNP syndrome.
AB  - Pathogenic disruptions to the activity-dependent neuroprotector homeobox (ADNP)
      gene are among the most common heterozygous genetic mutations associated with
      autism spectrum disorders (ASDs). Individuals with ADNP disruptions share a
      constellation of medical and psychiatric features, including ASD, intellectual
      disability (ID), dysmorphic features, and hypotonia. However, the profile of ASD
      symptoms associated with ADNP may differ from that of individuals with another
      ASD-associated single gene disruption or with ASD without a known genetic cause.
      The current study examined the ASD phenotype in a sample of representative youth
      with ADNP disruptions. Participants (N = 116, ages 4-22 years) included a cohort
      with ADNP mutations (n = 11) and three comparison groups with either a mutation
      to CHD8 (n = 11), a mutation to another ASD-associated gene (other mutation; n =
      53), or ASD with no known genetic etiology (idiopathic ASD; n = 41). As expected,
      individuals with ADNP disruptions had higher rates of ID but less severe social
      affect symptoms compared to the CHD8 and Idiopathic ASD groups. In addition,
      verbal intelligence explained more variance in social impairment in the ADNP
      group compared to CHD8, other mutation, and idiopathic ASD comparison groups.
      Restricted and repetitive behaviors in the ADNP group were characterized by high
      levels of stereotyped motor behaviors, whereas the idiopathic ASD group showed
      high levels of restricted interests. Taken together, these results underscore the
      role of ADNP in cognitive functioning and suggest that social impairments in ADNP
      syndrome are consistent with severity of verbal deficits. Autism Res 2018, 11:
      1300-1310. (c) 2018 International Society for Autism Research, Wiley Periodicals,
      Inc. LAY SUMMARY: Disruptions to the ADNP gene (i.e., ADNP syndrome) have been
      associated with autism spectrum disorder (ASD). This article describes
      intellectual disability, mild social difficulties, and severe repetitive motor
      movements in a group of 11 youth with ADNP Syndrome. We found lower rates of ASD
      than previously reported. Verbal skills explained individual variability in
      social impairment. This pattern suggests that the ADNP gene is primarily
      associated with learning and memory, and level of social difficulties is
      consistent with level of verbal impairment.

PMID- 30107087
TI  - Molecular dynamic simulations of the catalytic subunit of calpains 1, 2, 5, and
      10: Structural analysis with an aim toward drug design.
AB  - Calpains are cysteine proteases involved in the development of several human
      chronic illnesses such as neurodegenerative diseases, cardiovascular ailments,
      diabetes, and obesity which constitutes them into possible therapeutic targets.
      Here, using molecular dynamic simulations and docking, we studied the binding of
      known inhibitors to representative members of classical and nonclassical
      calpains. Our aim is to gain better understanding on the inhibition mechanism of
      calpains and to develop better and more specific inhibitors. Our atomistic models
      confirmed the importance of calcium ions for the structure of calpains and, as a
      consequence, their functionality. With these models and their subsequent use in
      molecular docking, essential structural requirements were identified for the
      binding of ligands to the calpain catalytic site that provide useful information
      for the design of new selective calpain inhibitors.

PMID- 30107086
TI  - Exosomal microRNAs as tumor markers in epithelial ovarian cancer.
AB  - Specific microRNAs (miRNAs) are packaged in exosomes that regulate processes in
      tumor development and progression. The current study focuses on the influence of
      exosomal miRNAs in the pathogenesis of epithelial ovarian cancer (EOC). MiRNA
      profiles were determined in exosomes from plasma of 106 EOC patients, eight
      ovarian cystadenoma patients, and 29 healthy women by TaqMan real-time PCR-based
      miRNA array cards containing 48 different miRNAs. In cell culture experiments,
      the impact of miR-200b and miR-320 was determined on proliferation and apoptosis
      of ovarian cancer cell lines. We report that miR-21 (P = 0.0001), miR-100 (P =
      0.034), miR-200b (P = 0.008), and miR-320 (P = 0.034) are significantly enriched,
      whereas miR-16 (P = 0.009), miR-93 (P = 0.014), miR-126 (P = 0.012), and miR-223
      (P = 0.029) are underrepresented in exosomes from plasma of EOC patients as
      compared to those of healthy women. The levels of exosomal miR-23a (P = 0.009,
      0.008) and miR-92a (P = 009, 0.034) were lower in ovarian cystadenoma patients
      than in EOC patients and healthy women, respectively. The exosomal levels of miR
      200b correlated with the tumor marker CA125 (P = 0.002) and patient overall
      survival (P = 0.019). MiR-200b influenced cell proliferation (P = 0.0001) and
      apoptosis (P < 0.008). Our findings reveal specific exosomal miRNA patterns in
      EOC and ovarian cystadenoma patients, which are indicative of a role of these
      miRNAs in the pathogenesis of EOC.

PMID- 30107088
TI  - Ipilimumab for the treatment of advanced melanoma in six kidney transplant
      patients.
AB  - Immune checkpoint inhibitors are new therapeutic options for metastatic melanoma,
      but few data are available in organ transplant recipient populations. Six French
      patients, three men and three women, mean age 66 years (range 44-74), all kidney
      transplant recipients, received ipilimumab (CTLA-4 inhibitor) for metastatic
      melanoma. At diagnosis of advanced melanoma, immunosuppressive therapy had been
      minimized in all but one. Adverse effects included one case of grade 1 diarrhea
      and one of grade 1 pruritus. One patient had acute T cell-mediated rejection
      confirmed by histology after the first injection of ipilimumab. After a median
      follow-up of 4.5 (3-20) months, one patient achieved partial response, one had
      stable disease, and four had disease progression. All the patients died, five
      from melanoma, one from another cause. In this series and in the literature,
      ipilimumab proved to be safe and possibly active. The acute rejection we
      encountered was probably related to both a rapid, drastic reduction of
      immunosuppression and the use of ipilimumab. Our safety data on ipilimumab
      contrast with the organ transplant rejections already reported with PD-1
      inhibitors. We consider that immunosuppression should not be minimized, as the
      impact on metastatic disease control is probably small.

PMID- 30107090
TI  - Tracking disease resistance deployment in potato breeding by enrichment
      sequencing.
AB  - Following the molecular characterisation of functional disease resistance genes
      in recent years, methods to track and verify the integrity of multiple genes in
      varieties are needed for crop improvement through resistance stacking. Diagnostic
      resistance gene enrichment sequencing (dRenSeq) enables the high-confidence
      identification and complete sequence validation of known functional resistance
      genes in crops. As demonstrated for tetraploid potato varieties, the methodology
      is more robust and cost-effective in monitoring resistances than whole-genome
      sequencing and can be used to appraise (trans) gene integrity efficiently. All
      currently known NB-LRRs effective against viruses, nematodes and the late blight
      pathogen Phytophthora infestans can be tracked with dRenSeq in potato and
      hitherto unknown polymorphisms have been identified. The methodology provides a
      means to improve the speed and efficiency of future disease resistance breeding
      in crops by directing parental and progeny selection towards effective
      combinations of resistance genes.

PMID- 30107091
TI  - The Open Circuit Voltage in Biofuel Cells: Nernstian Shift in Pseudocapacitive
      Electrodes.
AB  - In the development of biofuel cells great effort is dedicated to achieving
      outstanding figures of merit, such as high stability, maximum power output, and a
      large open circuit voltage. Biofuel cells with immobilized redox mediators, such
      as redox polymers with integrated enzymes, show experimentally a substantially
      higher open circuit voltage than the thermodynamically expected value. Although
      this phenomenon is widely reported in the literature, there is no comprehensive
      understanding of the potential shift, the high open circuit voltages have not
      been discussed in detail, and hence they are only accepted as an inherent
      property of the investigated systems. We demonstrate that this effect is the
      result of a Nernstian shift of the electrode potential when catalytic conversion
      takes place in the absence or at very low current flow. Experimental evidence
      confirms that the immobilization of redox centers on the electrode surface
      results in the assembled biofuel cell delivering a higher power output because of
      charge storage upon catalytic conversion. Our findings have direct implications
      for the design and evaluation of (bio)fuel cells with pseudocapacitive elements.

PMID- 30107092
TI  - The role of reduced expression of fragile X mental retardation protein in neurons
      and increased expression in astrocytes in idiopathic and syndromic autism
      (duplications 15q11.2-q13).
AB  - Fragile X syndrome (FXS), caused by lack of fragile X mental retardation protein
      (FMRP), is associated with a high prevalence of autism. The deficit of FMRP
      reported in idiopathic autism suggests a mechanistic overlap between FXS and
      autism. The overall goal of this study is to detect neuropathological
      commonalities of FMRP deficits in the brains of people with idiopathic autism and
      with syndromic autism caused by dup15q11.2-q13 (dup15). This study tests the
      hypothesis based on our preliminary data that both idiopathic and syndromic
      autism are associated with brain region-specific deficits of neuronal FMRP and
      structural changes of the affected neurons. This immunocytochemical study
      revealed neuronal FMRP deficits and shrinkage of deficient neurons in the
      cerebral cortex, subcortical structures, and cerebellum in subjects with
      idiopathic and dup(15)/autism. Neuronal FMRP deficit coexists with surprising
      infiltration of the brains of autistic children and adults with FMRP-positive
      astrocytes known to be typical only for the fetal and short postnatal periods. In
      the examined autistic subjects, these astrocytes selectively infiltrate the
      border between white and gray matter in the cerebral and cerebellar cortex, the
      molecular layer of the cortex, part of the amygdala and thalamus, central
      cerebellar white matter, and dentate nucleus. Astrocyte pathology results in an
      additional local loss of FMRP in neurons and their shrinkage. Neuronal deficit of
      FMRP and shrinkage of affected neurons in structures free of FMRP-positive
      astrocytes and regions infiltrated with FMRP-expressing astrocytes appear to
      reflect mechanistic, neuropathological, and functional commonalities of FMRP
      abnormalities in FXS and autism spectrum disorder. Autism Res 2018, 11: 1316
      1331. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc.
      LAY SUMMARY: Immunocytochemistry reveals a deficit of fragile X mental
      retardation protein (FMRP) in neurons of cortical and subcortical brain
      structures but increased FMRP expression in astrocytes infiltrating gray and
      white matter. The detected shrinkage of FMRP-deficient neurons may provide a
      mechanistic explanation of reported neuronal structural and functional changes in
      autism. This study contributes to growing evidence of mechanistic commonalities
      between fragile X syndrome and autism spectrum disorder.

PMID- 30107093
TI  - Adolescent bariatric surgery: a qualitative exploratory study of US patient
      perspectives.
AB  - Bariatric surgery is a safe and effective intervention to treat severe obesity
      and related comorbidities in adolescents. No qualitative studies have explored
      the perspectives of US adolescent weight-loss patients on their bariatric surgery
      motivations, decision-making or experiences. The purpose of this qualitative
      exploratory study was to explore the perspectives of adolescent patients seeking
      bariatric surgery while enrolled in a medical weight management programme.
      Eligible participants 13-21 years old were recruited through a weight management
      programme at a tertiary care children's hospital in the US Midwest. Interviews
      were conducted remotely using a video chat medium. An initial 60-min semi
      structured interview was conducted with seven participants who were 16-21 years
      old: one deciding on bariatric surgery, one pre-operative and five post
      operative. A brief follow-up interview was conducted 1 month later with four
      participants. Interviews were transcribed and coded using Atlas.ti software.
      Three broad themes emerged from participants' reflections: the long journey to
      surgery, time scarcity and be ready for change. The decision to pursue bariatric
      surgery takes place after struggling with obesity and failed weight-loss attempts
      since early childhood. Post-operative participants described bariatric surgery as
      life-changing, but determining when to schedule surgery is a challenge for
      adolescents.

PMID- 30107089
TI  - UBXN2A enhances CHIP-mediated proteasomal degradation of oncoprotein mortalin-2
      in cancer cells.
AB  - Overexpression of oncoproteins is a major cause of treatment failure using
      current chemotherapeutic drugs. Drug-induced degradation of oncoproteins is
      feasible and can improve clinical outcomes in diverse types of cancers. Mortalin
      2 (mot-2) is a dominant oncoprotein in several tumors, including colorectal
      cancer (CRC). In addition to inactivating the p53 tumor suppressor protein, mot-2
      enhances tumor cell invasion and migration. Thus, mot-2 is considered a potential
      therapeutic target in several cancer types. The current study investigated the
      biological role of a ubiquitin-like protein called UBXN2A in the regulation of
      mot-2 turnover. An orthogonal ubiquitin transfer technology followed by
      immunoprecipitation, in vitro ubiquitination, and Magnetic Beads TUBE2 pull-down
      experiments revealed that UBXN2A promotes carboxyl terminus of the HSP70
      interacting protein (CHIP)-dependent ubiquitination of mot-2. We subsequently
      showed that UBXN2A increases proteasomal degradation of mot-2. A subcellular
      compartmentalization experiment revealed that induced UBXN2A decreases the level
      of mot-2 and its chaperone partner, HSP60. Pharmacological upregulation of UBXN2A
      using a small molecule, veratridine (VTD), decreases the level of mot-2 in cancer
      cells. Consistent with the in vitro results, UBXN2A+/- mice exhibited selective
      elevation of mot-2 in colon tissues. An in vitro Anti-K48 TUBE isolation approach
      showed that recombinant UBXN2A enhances proteasomal degradation of mot-2 in mouse
      colon tissues. Finally, we observed enhanced association of CHIP with the UBXN2A
      mot-2 complex in tumors in an azoxymethane/dextran sulfate sodium-induced mouse
      CRC model. The existence of a multiprotein complex containing UBXN2A, CHIP, and
      mot-2 suggests a synergistic tumor suppressor activity of UBXN2A and CHIP in mot
      2-enriched tumors. This finding validates the UBXN2A-CHIP axis as a novel and
      potential therapeutic target in CRC.

PMID- 30107095
TI  - Controlled attenuation parameter (CAP) does not predict hepatic decompensation in
      patients with advanced chronic liver disease.
AB  - BACKGROUND&AIMS: Assessment of hepatic steatosis by transient elastography (TE)
      based controlled attenuation parameter (CAP) might predict hepatic
      decompensation. Therefore, we aimed to evaluate the prognostic value of CAP in
      patients with compensated advanced chronic liver disease (cACLD) and
      decompensated cirrhosis (DC). METHODS: 430 patients who underwent TE (liver
      stiffness >=10kPa) and CAP measurements were included in this retrospective
      analysis. The majority of patients (n=224) underwent simultaneous HVPG
      measurement. In cACLD-patients, first hepatic decompensation was defined by new
      onset of ascites, hepatic encephalopathy, or variceal bleeding. In patients with
      DC, the following events were considered as further hepatic decompensation:
      requirement of paracentesis, admission for/development of grade 3/4 hepatic
      encephalopathy, variceal (re-)bleeding, or liver-related death. RESULTS: First
      hepatic decompensation occurred in 25/292(9%) cACLD patients, while 46/138(33%)
      DC patients developed further hepatic decompensation during a median follow-up of
      22 and 12 months, respectively. CAP was not predictive of first (cACLD;per
      10dB/m;hazard ratio (HR):0.97,95% confidence interval (95%CI):0.91-1.03,p=0.321)
      or further hepatic decompensation (DC;HR:0.99,95%CI:0.94-1.03,p=0.554) in
      adjusted analysis. Using the well-established CAP-cut-off of >=248dB/m for
      hepatic steatosis, the incidence of first (cACLD;p=0.065) and further hepatic
      decompensation (DC;p=0.578) was similar in patients with hepatic steatosis, or
      without. Serum albumin levels (per mg/dL;HR:0.83,95%CI: 0.77-0.89,p<0.001) and
      MELD-Na (per point;HR:1.15,95%CI:1.04-1.28,p=0.006) in cACLD and MELD-Na (per
      point;HR:1.12,95%CI:1.05-1.19,p<0.0001) in DC patients were the only parameters
      independently associated with first and further hepatic decompensation,
      respectively. CONCLUSION: CAP does not predict the development of first
      (cACLD)/further (DC) hepatic decompensation, while serum albumin levels and MELD
      Na are of prognostic value. This article is protected by copyright. All rights
      reserved.

PMID- 30107094
TI  - Preclinical evidence of the enhanced effectiveness of combined rapamycin and
      AICAR in reducing kidney cancer.
AB  - Loss of Von Hippel-Lindau in renal carcinoma cells results in upregulation of the
      activity of hypoxia-inducible factor (HIF-alpha), a major transcription factor
      involved in kidney cancer. Rapamycin as mammalian target of rapamycin inhibitor
      and 5-aminoimidazole-4-carboxamide-riboside (AICAR) as AMPK activator are used
      separately to treat cancer patients. In the current study, the possible additive
      effect of drug combinations in reducing kidney tumorigenesis was investigated.
      Treatment with drug combinations significantly decreased cell proliferation,
      increased cell apoptosis, and abolished Akt phosphorylation and HIF-2alpha
      expression in renal cell carcinoma cells, including primary cells isolated from
      kidney cancer patients. Significant decreases in cell migration and invasion were
      detected using drug combinations. Drug combinations effectively abolished binding
      of HIF-2alpha to the Akt promoter and effected formation of the DNA-protein
      complex in nuclear extracts from 786-O cells, as demonstrated using
      electromobility shift assay and examination of Akt promoter activity.
      Importantly, we tested the effect of each drug and the combined drugs on kidney
      tumor size in the nude mouse model. Our data show that treatment with rapamycin,
      AICAR, and rapamycin+AICAR decreased tumor size by 38%, 36%, and 80%,
      respectively, suggesting that drug combinations have an additive effect in
      reducing tumor size compared with use of each drug alone. Drug combinations
      effectively decreased cell proliferation, increased apoptotic cells, and
      significantly decreased p-Akt, HIF-2alpha, and vascular endothelial growth factor
      expression in tumor kidney tissues from mice. These results show for the first
      time that drug combinations are more effective than single drugs in reducing
      kidney tumor progression. This study provides important evidence that may lead to
      the initiation of pre-clinical trials in patients with kidney cancer.

PMID- 30107096
TI  - Multiplexed fluorescence microscopy reveals heterogeneity among stromal cells in
      mouse bone marrow sections.
AB  - The bone marrow (BM) consists of multiple, structured micro-environmental
      entities-the so called niches, which contain hematopoietic cells as well as
      stromal cells. These niches fulfill a variety of functions, such as control of
      the hematopoietic stem cell pool, differentiation of hematopoietic cells, and
      maintenance of immunological memory. However, due to the molecular and cellular
      complexity and a lack of suitable histological multiplexing methods, the
      composition of the various BM niches is still elusive. In this study, we apply
      multiepitope-ligand-cartography (MELC) on bone sections from mice. We combine
      multiplexed immunofluorescence histology data with various object-based
      segmentation approaches in order to define irregularly shaped, net-like
      structures of stromal cells. We confirm MELC as a robust histological method and
      validate our automated segmentation algorithms using flow cytometry and manual
      evaluation. By means of MELC multiplexing, we reveal heterogeneous expression of
      leptin receptor (LpR), BP-1, and VCAM-1 in the stromal network. Moreover, we
      demonstrate by quantification a preferential contact of B cell subsets as well as
      of plasma cells to processes of CXCL12-expressing stromal cells, compared with
      stromal somata. In summary, our approach is suitable for spatial analysis of
      complex tissue structures.

PMID- 30107097
TI  - Beyond Friedel and Crafts: Directed Alkylation of C-H Bonds in Arenes.
AB  - The alkylation of arenes is one of the most fundamental transformations in
      chemical synthesis leading to privileged scaffolds in many areas of science.
      Classical methods for the introduction of alkyl groups to arenes are mostly based
      on the Friedel-Crafts reaction, radical additions, metallation or pre
      functionalization of the arene: these methods however suffer from limitations in
      scope, efficiency and selectivity. Moreover, they are based on the innate
      reactivity of the starting arene, favoring the alkylation at a certain position
      and rendering the introduction of alkyl chains at other positions much more
      challenging. This can be addressed by the use of a directing group facilitating,
      in the presence of a metal catalyst, the regioselective alkylation of a C-H bond.
      These directed alkylations of C-H bonds in arenes are overviewed, in a
      comprehensive manner, in this review article.

PMID- 30107098
TI  - Comparison of JC-1 and MitoTracker probes for mitochondrial viability assessment
      in stored canine platelet concentrates: A flow cytometry study.
AB  - Mitochondria perform crucial roles in many biochemical processes, and
      mitochondrial depolarization is an early sign of platelet apoptosis. The
      mitochondrial membrane potential is usually evaluated through JC-1 probe, but it
      can also be assessed with MitoTracker probes. Our aim was to evaluate
      mitochondrial viability in stored canine platelet concentrates (PCs) with the
      fluorescent probes JC-1 and MitoTracker. Platelets from 22 canine PCs were
      stained with JC-1 and MitoTracker probes on days 1, 3, and 5 of storage. Data on
      metabolic parameters were also collected for correlation studies. Results of JC-1
      and MitoTracker revealed a decrease in mitochondrial membrane potential in day 5
      of storage compared to days 1 and 3, providing evidence of mitochondrial
      depolarization, a finding that was confirmed by the data on metabolic parameters.
      MitoTracker probes also added information regarding platelet swelling. In
      conclusion, MitoTracker probes offered a more complete mitochondrial analysis in
      the evaluation of stored canine PCs.

PMID- 30107099
TI  - Background fluorescence and spreading error are major contributors of variability
      in high-dimensional flow cytometry data visualization by t-distributed stochastic
      neighboring embedding.
AB  - Multidimensional single-cell analysis requires approaches to visualize complex
      data in intuitive 2D graphs. In this regard, t-distributed stochastic neighboring
      embedding (tSNE) is the most popular algorithm for single-cell RNA sequencing and
      cytometry by time-of-flight (CyTOF), but its application to polychromatic flow
      cytometry, including the recently developed 30-parameter platform, is still under
      investigation. We identified differential distribution of background values
      between samples, generated by either background calculation or spreading error
      (SE), as a major source of variability in polychromatic flow cytometry data
      representation by tSNE, ultimately resulting in the identification of erroneous
      heterogeneity among cell populations. Biexponential transformation of raw data
      and limiting SE during panel development dramatically improved data
      visualization. These aspects must be taken into consideration when using
      computational approaches as discovery tools in large sets of samples from
      independent experiments or immunomonitoring in clinical trials.

PMID- 30107100
TI  - Trimethoprim-Sulfamethoxazole-Induced Exacerbation of Anxiety and Depression.

PMID- 30107101
TI  - Obstructive Sleep Apnea in Posttraumatic Stress Disorder Comorbid With Mood
      Disorder: Significantly Higher Incidence Than in Either Diagnosis Alone.
AB  - Objective: To examine the correlations between obstructive sleep apnea (OSA) and
      psychiatric disorders such as major depressive disorder (MDD), posttraumatic
      stress disorder (PTSD), or bipolar disorder (BD) and whether comorbid psychiatric
      diagnosis increases the risk of OSA. Methods: This retrospective chart review
      study included all patients (N = 413) seen within a randomly selected 4-month
      period (August 2014 to November 2014) in a Veterans Administration outpatient
      psychiatry clinic. Patients were screened for symptoms of OSA with the STOP-BANG
      Questionnaire. Those with a positive screen were referred to the sleep clinic for
      confirmation of the diagnosis by polysomnogram (PSG). Frequency of PSG-confirmed
      OSA was correlated with different psychiatric disorders and comorbid psychiatric
      diagnoses. Results: The study showed a high prevalence of OSA in psychiatric
      patients, particularly with MDD (37.8%) and PTSD (35.5%) and less so with BD
      (16.7%). Among all patients with OSA (n = 155), those with comorbid BD and PTSD
      had a significantly higher rate of OSA than those with BD alone (chi2 = 7.28, P <
      .05) but not with PTSD alone. We also found a statistically significant higher
      incidence of OSA in male veterans with either MDD comorbid with PTSD (chi2 =
      3.869, P < .05) or BD comorbid with PTSD (chi2 = 6.631, P < .05) compared with
      either mood disorder or PTSD alone. Conclusions: The study showed a high
      prevalence of OSA in psychiatric patients, particularly in those with PTSD and
      MDD and less so with BD. There was a statistically significant increase in the
      incidence of OSA in male veterans with either BD with comorbid PTSD or MDD with
      comorbid PTSD..

PMID- 30107102
TI  - Tramadol: Relieves Pain, Improves Mood, Induces Mania.

PMID- 30107103
TI  - Physician Well-Being: Foreword.

PMID- 30107104
TI  - Physician Well-Being: Physician Burnout.
AB  - Physician burnout affects patients and physicians. Recent studies estimate that
      more than half of all physicians in the United States currently are experiencing
      burnout. Burnout can include symptoms of emotional exhaustion, depersonalization,
      cognitive weariness, physical fatigue, and disengagement. It can lead to physical
      and psychological conditions in physicians and decrease patient safety, quality
      of care, and satisfaction. The health care work environment appears to be the
      main contributing factor in the current high rates of physician burnout. Although
      individual- and organizational-level interventions appear to be effective in
      reducing burnout, there is no conclusive evidence regarding which intervention or
      combination of interventions alleviates symptoms. Physicians can reduce burnout
      with use of mindfulness and stress management techniques. Beyond the level of the
      individual physician, employers and payers should recognize the benefits of
      supporting physician well-being and making medical practice a rewarding and
      healthy experience.

PMID- 30107105
TI  - Physician Well-Being: Improving Office Efficiency.
AB  - Improving office efficiency can contribute to physician well-being by increasing
      the amount of time physicians spend with patients while decreasing the amount of
      time spent on administrative and regulatory requirements. Delegation of
      administrative tasks (such as those involving electronic health records [EHRs])
      to scribes and prior authorization duties to staff members improves job
      satisfaction. Customization of EHR templates can expedite workflow and improve
      quality of care. Optimization of drug prescribing can reduce the number of refill
      requests needed and decrease workload. Reducing rates of missed appointments,
      creating a system to address late arrivals, and offering a variety of visit
      lengths and types reduce staff overtime while improving patient outcomes. Use of
      team huddles improves consistency and communication. The presence of on-site
      mental health and pharmacy services has been shown to improve physician
      satisfaction with treatment access and coordination of care.

PMID- 30107106
TI  - Physician Well-Being: Organizational Strategies for Physician Burnout.
AB  - Until recently, most initiatives to address physician burnout have focused on
      improving the resilience of individual physicians. These measures are necessary
      but insufficient since it is now recognized that organizations have a major role
      in causing, preventing, and mitigating physician burnout. Burnout must be
      addressed by organizational change. The first steps to improving clinician well
      being are measurement and monitoring. Several validated scales are available to
      assess well-being. Results of assessments can be used to engage clinicians in
      open conversations on issues and potential solutions. Specific leadership
      behaviors and positive organizational cultures decrease burnout and enhance
      engagement. There must be an institutional commitment to enhancing physician
      autonomy and transparent communication, improving the meaning of work, reducing
      administrative and regulatory burdens, and reducing the stigma related to seeking
      care.

PMID- 30107107
TI  - Physician Well-Being: Financial Aspects.
AB  - The US health care system has an unequal distribution of physician supply, is
      poorly accessible in some areas, and has wide disparities in patient health
      status. The Patient Protection and Affordable Care Act (ACA) was intended to
      address these issues by providing affordable health insurance coverage, Medicaid
      expansion, and care delivery system redesign (particularly through physician
      payment reform). As part of payment reform, the Medicare Access and CHIP
      Reauthorization Act (MACRA) went into effect in January 2017. Under MACRA,
      physicians receive payment under the Quality Payment Program (QPP). Starting
      January 1, 2019, the QPP pays physicians Medicare part B payments based on their
      2017 performance via one of two ways: an advanced alternative payment model or
      the Merit-Based Incentive Payment System (MIPS). Most physicians will be placed
      in the MIPS. This shift to performance-based payment requires practices to
      optimize financial aspects of practice management and improve critical workflows
      and care delivery processes.

PMID- 30107109
TI  - H2 Cleavage by Frustrated Lewis Pairs Characterized by the Energy Decomposition
      Analysis of Transition States: An Alternative to the Electron Transfer and
      Electric Field Models.
AB  - Knowing that the Papai's electron transfer (ET) and the Grimme's electric field
      (EF) models draw attention to somewhat different physical aspects, we are going
      to systematically (re)examine interactions in the transition states (TSs) of the
      heterolytic H2-cleavage by the Frustrated Lewis Pairs (FLPs). Our main vehicle is
      the quantitative energy decomposition analysis (EDA), a powerful method for
      elucidation of interactions, plus the analysis of molecular orbitals (MOs).
      Herein, the Lewis acid (LA) is B(C6F5)3 and the Lewis bases (LBs) are tBu3P, ( o
      C6H4Me)3P, 2,6-lutidine, 2,4,6-lutidine, MeN?C(Ph)Me imine, MeN(H)-C(H)PhMe
      amine, THF, 1,4-dioxane, and acetone. For a series of the phosphorus-, nitrogen-,
      and oxygen-bearing LBs plus B(C6F5)3, we will show that (i) neither the
      electrostatic nor the orbital interactions dominate but instead both are
      essential alongside the Pauli repulsion and (ii) the frontier molecular orbitals
      (FMOs) of a TS can arise not only from the "push-pull" molecular orbital scheme
      by Papai et al., which directly involves the occupied sigma and the empty sigma*
      MOs of H2, but also from a more intricate but energetically more fitting orbital
      interactions which have escaped notice thus far.

PMID- 30107108
TI  - High-Performance 0-3 Type Niobate-Based Lead-Free Piezoelectric Composite
      Ceramics with ZnO Inclusions.
AB  - Because of their high toxicity, lead-based materials in electronic devices must
      be replaced by lead-free piezoelectric materials. However, some issues remain
      that hinder the industrial applications of these alternative ceramics. Here, we
      report the construction of a 0-3-type ceramic composite (KNNS-BNKZ: xZnO), where
      the Sb-doped ZnO submicronic particles were randomly distributed throughout the
      potassium-sodium niobate-based ceramic matrix. In this (K,Na)NbO3 (KNN)-based
      ceramic composite, superior temperature stability, excellent piezoelectric
      properties, and a high Curie temperature were simultaneously achieved. The
      unipolar strain varied from +20 to -16% when the temperature was increased from
      23 to 200  degrees C in KNNS-BNKZ: xZnO with x = 0.75. By increasing the ZnO
      content from x = 0 to x = 5.0, the Curie temperature was increased from 227 to
      294  degrees C. More importantly, the piezoelectric coefficient remained high (
      d33 = 480-510 pC/N) for a wide range of compositions, x = 0.25-1.0. Transmission
      electron microscopy (TEM) experiments showed that the compensatory electric
      fields generated by the Sb-doped ZnO submicronic particles were responsible for
      the improved temperature stability. The high piezoelectricity was due to the
      existence of nanodomains, which were clearly observed in the TEM experiments. The
      results presented in this work clarify some of the physical mechanisms in this
      KNN-based ceramic composite, thus advancing the development of lead-free
      ceramics.

PMID- 30107110
TI  - Rational Design of Hierarchical Titanium Nitride@Vanadium Pentoxide Core-Shell
      Heterostructure Fibrous Electrodes for High-Performance 1.6 V Nonpolarity
      Wearable Supercapacitors.
AB  - Extensive progress has been made in fiber-shaped asymmetric supercapacitors
      (FASCs) for portable and wearable electronics. However, positive and negative
      electrodes must be distinguished and low energy densities are a crucial challenge
      and thus limit their practical applications. This paper reports an efficient
      method to directly grow TiN nanowire arrays@V2O5 nanosheets core-shell
      heterostructures on carbon nanotube fibers as nonpolarity electrodes. Benefiting
      from their unique heterostructure, single electrodes possess high specific
      capacitances of 195.1 and 230.7 F cm-3 as positive and negative electrodes,
      respectively. Furthermore, all-solid-state nonpolarity FASC devices with a
      maximum voltage of 1.6 V were successfully fabricated. Our devices achieve an
      outstanding specific capacitance of 74.25 F cm-3 and a remarkable energy density
      of 26.42 mW h cm-3. More importantly, their electrochemical performance changed
      negligibly regardless of whether the charge-discharge process is in positive or
      negative direction, indicating excellent nonpolarity. Therefore, these high
      performance nonpolarity FASCs pave the way for next-generation wearable energy
      storage devices.

PMID- 30107111
TI  - Structure-Activity Relationship of Flavin Analogues That Target the Flavin
      Mononucleotide Riboswitch.
AB  - The flavin mononucleotide (FMN) riboswitch is an emerging target for the
      development of novel RNA-targeting antibiotics. We previously discovered an FMN
      derivative, 5FDQD, that protects mice against diarrhea-causing Clostridium
      difficile bacteria. Here, we present the structure-based drug design strategy
      that led to the discovery of this fluoro-phenyl derivative with antibacterial
      properties. This approach involved the following stages: (1) structural analysis
      of all available free and bound FMN riboswitch structures; (2) design, synthesis,
      and purification of derivatives; (3) in vitro testing for productive binding
      using two chemical probing methods; (4) in vitro transcription termination
      assays; and (5) resolution of the crystal structures of the FMN riboswitch in
      complex with the most mature candidates. In the process, we delineated principles
      for productive binding to this riboswitch, thereby demonstrating the
      effectiveness of a coordinated structure-guided approach to designing drugs
      against RNA.

PMID- 30107112
TI  - Diatom Microbubbler for Active Biofilm Removal in Confined Spaces.
AB  - Bacterial biofilms form on and within many living tissues, medical devices, and
      engineered materials, threatening human health and sustainability. Removing
      biofilms remains a grand challenge despite tremendous efforts made so far,
      particularly when they are formed in confined spaces. One primary cause is the
      limited transport of antibacterial agents into extracellular polymeric substances
      (EPS) of the biofilm. In this study, we hypothesized that a microparticle
      engineered to be self-locomotive with microbubbles would clean a structure fouled
      by biofilm by fracturing the EPS and subsequently improving transports of the
      antiseptic reagent. We examined this hypothesis by doping a hollow cylinder
      shaped diatom biosilica with manganese oxide (MnO2) nanosheets. In an antiseptic
      H2O2 solution, the diatoms doped by MnO2 nanosheets, denoted as diatom bubbler,
      discharged oxygen gas bubbles continuously and became self-motile. Subsequently,
      the diatoms infiltrated the bacterial biofilm formed on either flat or
      microgrooved silicon substrates and continued to generate microbubbles. The
      resulting microbubbles merged and converted surface energy to mechanical energy
      high enough to fracture the matrix of biofilm. Consequently, H2O2 molecules
      diffused into the biofilm and killed most bacterial cells. Overall, this study
      provides a unique and powerful tool that can significantly impact current efforts
      to clean a wide array of biofouled products and devices.

PMID- 30107113
TI  - Material-Versatile Ultrabroadband Light Absorber with Self-Aggregated Multiscale
      Funnel Structures.
AB  - Broadband light absorbers are essential components for a variety of applications,
      including energy harvesting and optoelectronic devices. Thus, the development of
      a versatile absorbing structure that is applicable in various operating
      environments is required. In this study, a material-versatile ultrabroadband
      absorber consisting of metal-coated self-aggregated Al2O3 nanowire bundles with
      multiscale funnel structures is fabricated. A high absorptance of ~0.9 over the
      AM 1.5G spectrum (300-2500 nm) is realized for absorbers with a range of metal
      coatings, including Al, W, and titanium nitride (TiN). We demonstrate that the
      plasmonic nanofocusing and index-matching effects of the funnel structure result
      in strong ultrabroadband absorption for the various metal coatings, even though
      the coating materials have different optical properties. As an example of
      applicability in an operating environment, in the evaluation of the thermal
      oxidation resistance, the Al-coated solar absorber exhibits superior performance
      to those coated with refractory materials such as W and TiN because of the
      protective alumina layer formed on the Al surface.

PMID- 30107114
TI  - Crude-Oil-Repellent Membranes by Atomic Layer Deposition: Oxide Interface
      Engineering.
AB  - Crude oil fouling on membrane surfaces is a persistent, crippling challenge in
      oil spill remediation and oilfield wastewater treatment. In this research, we
      present how a nanosized oxide coating can profoundly affect the anti-crude-oil
      property of membrane materials. Select oxide coatings with a thickness of ~10 nm
      are deposited conformally on common polymer membrane surfaces by atomic layer
      deposition to significantly mitigate fouling during filtration processes. TiO2-
      and SnO2-coated membranes exhibited far greater anti-crude-oil performance than
      ZnO- and Al2O3-coated ones. Tightly bound hydration layers play a crucial role in
      protecting the surface from crude oil adhesion, as revealed by molecular dynamics
      simulations. This work provides a facile strategy to fabricate crude-oil
      resistant membranes with negligible impact on membrane structure, and also
      demonstrates that, contrary to common belief, excellent crude oil resistance can
      be achieved easily without implementation of sophisticated, hierarchical
      structures.

PMID- 30107115
TI  - Halide-, Hybrid-, and Perovskite-Functionalized Light Absorbing Quantum Materials
      of p-i-n Heterojunction Solar Cells.
AB  - The p-i-n quantum dot (QD) solar cells were fabricated through the single-step
      deposition of both of its p-type and light absorbing quantum layers. The hole
      transport and light absorbing layers of these devices were made by the p- and n
      type PbS QDs, which were functionalized with mercaptopropionic acid and different
      halide, hybrid, and perovskite ligands, respectively. Fabrication of such p-i-n
      devices by the single-step deposition of pre-exchanged colloidal QDs had not been
      fully investigated so far because of the low progression of ligand exchange
      processes, weak colloidal stability of pre-exchanged QDs in desired solvents, and
      remaining of the ligand exchange products along with particles. However, we
      showed that the type of ligand complexes, amino acid products of ligand exchange,
      and protic solvents are highly effective for increasing the ligand exchange
      progression and preparation of high colloidal stability QDs with superior
      photoluminescence properties. As well, the surface chemistry investigations by
      the means of Fourier transform infrared, nuclear magnetic resonance, X-ray
      photoelectron spectroscopy, X-ray diffraction, inductively coupled plasma optical
      emission spectrometry, carbon-hydrogen-nitrogen-sulfur elemental analysis, zeta
      potential, and high-resolution transmission electron microscopy were led to the
      presentation of new concepts about the theoretical and experimental ligand weight
      percentages, the mechanisms of solution-phase ligand exchange processes, and
      formation of ligands adlayer on the (111) facets of QDs. The pre-exchanged
      colloidal QDs showed very good desirability for the single-step deposition of
      dense, defects-free, and smooth QD layers. Regarding that, the p-i-n solar cells
      were successfully fabricated by the single-step deposition of both of the QD
      layers. Especially, the highest power conversion efficiency value of 6.40% was
      recorded for the devices in which the light absorbing layer was prepared by the
      composite-like QD-perovskite structures.

PMID- 30107116
TI  - Tuning Band Gap and Work Function Modulations in Monolayer hBN/Cu(111)
      Heterostructures with Moire Patterns.
AB  - The moire pattern formed between a two-dimensional (2D) material and the
      substrate has played a crucial role in tuning the electronic structure of the 2D
      material. Here, by using scanning tunneling microscopy and spectroscopy, we found
      a moire-pattern-dependent band gap and work function modulation in hexagonal
      boron nitride (hBN)/Cu(111) heterostructures, whose amplitudes increase with the
      moire pattern wavelength. Moreover, the work function modulation shifts agree
      well with the conduction band edge shifts, indicating a spatially constant
      electron affinity for the hBN layer. Density functional theory calculations
      showed that these observations in hBN/Cu(111) heterostructures mainly originated
      from the hybridization of the N 3p z orbital and Cu 4s orbital in different
      atomic configurations. Our results show that the twist-angle dependence of moire
      patterns in hBN/Cu(111) heterostructures can be used to tailor the electronic
      properties including band gap and work function.

PMID- 30107117
TI  - In Vivo Chemical Monitoring at High Spatiotemporal Resolution Using
      Microfabricated Sampling Probes and Droplet-Based Microfluidics Coupled to Mass
      Spectrometry.
AB  - An essential approach for in vivo chemical monitoring is to use sampling probes
      coupled with analytical methods; however, this method traditionally has limited
      spatial and temporal resolution. To address this problem, we developed an
      analytical system that combines microfabricated push-pull sampling probes with
      droplet-based microfluidics. The microfabricated probe provides spatial
      resolution approximately 1000-fold better than that of common microdialysis
      probes. Microfabrication also facilitated integration of an extra channel into
      the probe for microinjection. We created microfluidic devices and interfaces that
      allowed manipulation of nanoliter droplet samples collected from the
      microfabricated probe at intervals of a few seconds. Use of droplet-based
      microfluidics prevented broadening of collected zones, yielding 6 s temporal
      resolution at 100 nL/min perfusion rates. Resulting droplets were analyzed by
      direct infusion nanoelectrospray ionization (nESI) mass spectrometry for
      simultaneous determination of glutamine, glutamate, gamma-aminobutyric acid, and
      acetylcholine. Use of low infusion rates that enabled nESI (50 nL/min) was
      critical to allowing detection in the complex samples. Addition of 13C-labeled
      internal standards to the droplet samples was used for improved quantification.
      Utility of the overall system was demonstrated by monitoring dynamic chemical
      changes evoked by microinjection of high potassium concentrations into the brain
      of live rats. The results showed stimulated neurochemical release with rise times
      of 15 s. This work demonstrates the potential of coupling microfabricated
      sampling probes to droplet-based mass spectrometric assays for studying chemical
      dynamics in a complex microenvironment at high spatiotemporal resolution.

PMID- 30107118
TI  - Molecular Dynamics Simulations of Furfural and 5-Hydroxymethylfurfural at Ambient
      and Hydrothermal Conditions.
AB  - In this work, we present results from molecular dynamics simulations of aqueous
      solutions of furfural and 5-hydroxymethylfurfural, which are important
      intermediates in the hydrothermal carbonization processes of biomass conversion.
      The computations were performed both at ambient and hydrothermal conditions using
      a two-level factorial design varying concentration, temperature, and pressure. A
      number of equilibrium and dynamic properties have been computed including
      enthalpies and free energies of vaporization, free energies of solvation,
      diffusion coefficients, and rotational/reorientational correlation times.
      Structural properties of solutions were analyzed using radial and spatial
      distribution functions. It was shown that the formation of hydrogen bonds among 5
      hydroxymethylfurfural molecules is preferred compared to hydrogen bonding between
      5-hydroxymethylfurfural and water. In addition, our results suggest that the
      oxygen atoms in the furan rings of furfural and 5-hydroxymethylfurfural do not
      participate in hydrogen bonding to the same extent as the oxygen atoms in the
      hydroxyl and carbonyl groups. It is also observed that furfural molecules
      aggregate under certain conditions, and we show how this is affected by changes
      in temperature, pressure, and concentration in agreement with experimental
      solubility data. The analysis of the computational results provides useful
      insight into the structure and dynamics of the considered molecules at conditions
      of hydrothermal carbonization, as well as at ambient conditions.

PMID- 30107119
TI  - New Method To Extract Final-State Information of Polyatomic Reactions Based on
      Normal Mode Analysis.
AB  - State-to-state reaction dynamics provides a comprehensive insight into reaction
      mechanisms of chemical reactions at the atomic level. A new scheme to extract
      final-state information based on normal mode analysis is proposed in this work.
      Different from the traditional scheme extracting the coordinates and momenta from
      the last step of each trajectory, they are taken in the new scheme from a
      specific step of each reactive trajectory within the last vibrational period of
      the product molecule by demanding the corresponding geometry of the step to have
      the minimum potential energy. Test calculations on the collisions between the
      atom H and the molecules H2O, H2S, and NH3 show that the new scheme works much
      better than the traditional one. In addition, the new scheme is applied to
      calculate the vibrational state distribution of the product NH2 in the reaction H
      + NH3 -> H2 + NH2.

PMID- 30107120
TI  - Spatial-Temporal Characteristics of Confined Polymer Motion Determine Proton
      Conduction of Polyoxometalate-Poly(ethylene glycol) Hybrid Nanocomposites.
AB  - Highly efficient proton conductors, polyoxometalate-poly(ethylene glycol) (POM
      PEG) hybrid nanocomposites, have been synthesized by encapsulating a single PEG
      chain inside the 1D nanochannel defined by the frameworks of POMs. By employing
      two types of neutron scattering techniques complemented by thermal analysis, we
      prove that in a nanochannel a single PEG chain stays as a distorted helix. More
      importantly, we reveal that the PEG segments perform a localized longitudinal
      random walk and quantitatively show the strong correlation between the local
      motion of PEG and the macroscopic proton conduction of the material. On the basis
      of these spatial-temporal characteristics, a microscopic picture for the proton
      conduction process of POM-PEG hybrid materials is proposed.

PMID- 30107121
TI  - Materials Characterization by Dynamic Nuclear Polarization-Enhanced Solid-State
      NMR Spectroscopy.
AB  - High-resolution solid-state NMR spectroscopy is a powerful tool for the study of
      organic and inorganic materials because it can directly probe the symmetry and
      structure at nuclear sites, the connectivity/bonding of atoms and precisely
      measure interatomic distances. However, NMR spectroscopy is hampered by
      intrinsically poor sensitivity; consequently, the application of NMR spectroscopy
      to many solid materials is often infeasible. High-field dynamic nuclear
      polarization (DNP) has emerged as a technique to routinely enhance the
      sensitivity of solid-state NMR experiments by 1-3 orders of magnitude. This
      Perspective gives a general overview of how DNP-enhanced solid-state NMR
      spectroscopy can be applied to a variety of inorganic and organic materials. DNP
      enhanced solid-state NMR experiments provide unique insights into the molecular
      structure, which makes it possible to form structure-activity relationships that
      ultimately assist in the rational design and improvement of materials.

PMID- 30107122
TI  - Establishing a High-Yielding Cell-Free Protein Synthesis Platform Derived from
      Vibrio natriegens.
AB  - A new wave of interest in cell-free protein synthesis (CFPS) systems has shown
      their utility for producing proteins at high titers, establishing genetic
      regulatory element libraries ( e.g., promoters, ribosome binding sites) in
      nonmodel organisms, optimizing biosynthetic pathways before implementation in
      cells, and sensing biomarkers for diagnostic applications. Unfortunately, most
      previous efforts have focused on a select few model systems, such as Escherichia
      coli. Broadening the spectrum of organisms used for CFPS promises to better mimic
      host cell processes in prototyping applications and open up new areas of
      research. Here, we describe the development and characterization of a facile CFPS
      platform based on lysates derived from the fast-growing bacterium Vibrio
      natriegens, which is an emerging host organism for biotechnology. We demonstrate
      robust preparation of highly active extracts using sonication, without
      specialized and costly equipment. After optimizing the extract preparation
      procedure and cell-free reaction conditions, we show synthesis of 1.6 +/- 0.05
      g/L of superfolder green fluorescent protein in batch mode CFPS, making it
      competitive with existing E. coli CFPS platforms. To showcase the flexibility of
      the system, we demonstrate that it can be lyophilized and retain biosynthesis
      capability, that it is capable of producing antimicrobial peptides, and that our
      extract preparation procedure can be coupled with the recently described Vmax
      Express strain in a one-pot system. Finally, to further increase system
      productivity, we explore a knockout library in which putative negative effectors
      of CFPS are genetically removed from the source strain. Our V. natriegens-derived
      CFPS platform is versatile and simple to prepare and use. We expect it will
      facilitate expansion of CFPS systems into new laboratories and fields for
      compelling applications in synthetic biology.

PMID- 30107123
TI  - Virtual Screening and Experimental Testing of B1 Metallo-beta-lactamase
      Inhibitors.
AB  - The global rise of metallo-beta-lactamases (MBLs) is problematic due to their
      ability to inactivate most beta-lactam antibiotics. MBL inhibitors that could be
      coadministered with and restore the efficacy of beta-lactams are highly sought
      after. In this study, we employ virtual screening of candidate MBL inhibitors
      without thiols or carboxylates to avoid off-target effects using the Avalanche
      software package, followed by experimental validation of the selected compounds.
      As target enzymes, we chose the clinically relevant B1 MBLs NDM-1, IMP-1, and VIM
      2. Among 32 compounds selected from an approximately 1.5 million compound
      library, 6 exhibited IC50 values less than 40 MUM against NDM-1 and/or IMP-1. The
      most potent inhibitors of NDM-1, IMP-1, and VIM-2 had IC50 values of 19 +/- 2, 14
      +/- 1, and 50 +/- 20 MUM, respectively. While chemically diverse, the most potent
      inhibitors all contain combinations of hydroxyl, ketone, ester, amide, or
      sulfonyl groups. Docking studies suggest that these electron-dense moieties are
      involved in Zn(II) coordination and interaction with protein residues. These
      novel scaffolds could serve as the basis for further development of MBL
      inhibitors. A procedure for renaming NDM-1 residues to conform to the class B
      beta-lactamase (BBL) numbering scheme is also included.

PMID- 30107124
TI  - Photoinduced Enhanced Raman from Lithium Niobate on Insulator Template.
AB  - Photoinduced enhanced Raman spectroscopy from a lithium niobate on insulator
      (LNOI)-silver nanoparticle template is demonstrated both by irradiating the
      template with 254 nm ultraviolet (UV) light before adding an analyte and before
      placing the substrate in the Raman system (substrate irradiation) and by
      irradiating the sample in the Raman system after adding the molecule (sample
      irradiation). The photoinduced enhancement enables up to an ~sevenfold increase
      of the surface-enhanced Raman scattering signal strength of an analyte following
      substrate irradiation, whereas an ~threefold enhancement above the surface
      enhanced signal is obtained for sample irradiation. The photoinduced enhancement
      relaxes over the course of ~10 h for a substrate irradiation duration of 150 min
      before returning to initial signal levels. The increase in Raman scattering
      intensity following UV irradiation is attributed to photoinduced charge transfer
      from the LNOI template to the analyte. New Raman bands are observed following UV
      irradiation, the appearance of which is suggestive of a photocatalytic reaction
      and highlight the potential of LNOI as a photoactive surface-enhanced Raman
      spectroscopy substrate.

PMID- 30107125
TI  - Synthesis of RNA Nucleotides in Plausible Prebiotic Conditions from ab Initio
      Computer Simulations.
AB  - Understanding the mechanism of spontaneous formation of ribonucleotides under
      realistic prebiotic conditions is a key open issue of origins-of-life research.
      In cells, de novo and salvage nucleotide enzymatic synthesis combines 5-phospho
      alpha-d-ribose-1-diphosphate (alpha-PRPP) and nucleobases. Interestingly, these
      reactants are also known as prebiotically plausible compounds. Combining ab
      initio molecular dynamics simulations with recently developed reaction
      exploration and enhanced sampling methods, we show that nucleobases and alpha
      PRPP should spontaneously combine, under mild hydrothermal conditions, with an
      exothermic reaction and a facile mechanism, forming both purine and pyrimidine
      ribonucleotides. Surprisingly, this mechanism is very similar to the biological
      one and yields ribonucleotides with the same anomeric carbon chirality as in
      biological systems. Mass spectrometry experiments performed on solutions of
      adenine and PRPP in similar conditions support the formation of AMP. These
      results suggest that natural selection might have optimized, through enzymes, a
      pre-existing ribonucleotide formation mechanism, carrying it forward to modern
      life forms.

PMID- 30107126
TI  - Non-heme High-Spin {FeNO}6-8 Complexes: One Ligand Platform Can Do It All.
AB  - Heme and non-heme iron-nitrosyl complexes are important intermediates in biology.
      While there are numerous examples of low-spin heme iron-nitrosyl complexes in
      different oxidation states, much less is known about high-spin (hs) non-heme iron
      nitrosyls in oxidation states other than the formally ferrous NO adducts ({FeNO}7
      in the Enemark-Feltham notation). In this study, we present a complete series of
      hs-{FeNO}6-8 complexes using the TMG3tren coligand. Redox transformations from
      the hs-{FeNO}7 complex [Fe(TMG3tren)(NO)]2+ to its {FeNO}6 and {FeNO}8 analogs do
      not alter the coordination environment of the iron center, allowing for detailed
      comparisons between these species. Here, we present new MCD, NRVS, XANES/EXAFS,
      and Mossbauer data, demonstrating that these redox transformations are metal
      based, which allows us to access hs-Fe(II)-NO-, Fe(III)-NO-, and Fe(IV)-NO-
      complexes. Vibrational data, analyzed by NCA, directly quantify changes in Fe-NO
      bonding along this series. Optical data allow for the identification of a
      "spectator" charge-transfer transition that, together with Mossbauer and XAS
      data, directly monitors the electronic changes of the Fe center. Using EXAFS, we
      are also able to provide structural data for all complexes. The magnetic
      properties of the complexes are further analyzed (from magnetic Mossbauer). The
      properties of our hs-{FeNO}6-8 complexes are then contrasted to corresponding,
      low-spin iron-nitrosyl complexes where redox transformations are generally NO
      centered. The hs-{FeNO}8 complex can further be protonated by weak acids, and the
      product of this reaction is characterized. Taken together, these results provide
      unprecedented insight into the properties of biologically relevant non-heme iron
      nitrosyl complexes in three relevant oxidation states.

PMID- 30107127
TI  - beta-Cyclodextrin-Functionalized Chitosan/Alginate Compact Polyelectrolyte
      Complexes (CoPECs) as Functional Biomaterials with Anti-Inflammatory Properties.
AB  - Nowadays, the need for therapeutic biomaterials displaying anti-inflammatory
      properties to fight against inflammation-related diseases is continuously
      increasing. Compact polyelectrolyte complexes (CoPECs) represent a new class of
      materials obtained by ultracentrifugation of a polyanion/polycation complex
      suspension in the presence of salt. Here, a noncytotoxic beta-cyclodextrin
      functionalized chitosan/alginate CoPEC was formulated, characterized, and
      described as a promising drug carrier displaying an intrinsic anti-inflammatory
      property. This new material was successfully formed, and due to the presence of
      cyclodextrins, it was able to trap and release hydrophobic drugs such as
      piroxicam used as a model drug. The intrinsic anti-inflammatory activity of this
      CoPEC was analyzed in vitro using murine macrophages in the presence of
      lipopolysaccharide (LPS) endotoxin. In this model, it was shown that CoPEC
      inhibited LPS-induced TNF-alpha and NO release and moderated the differentiation
      of LPS-activated macrophages. Over time, this kind of bioactive biomaterial could
      constitute a new family of delivery systems and expand the list of therapeutic
      tools available to target inflammatory chronic diseases such as arthritis or
      Crohn's disease.

PMID- 30107128
TI  - Lattice Dynamics and Thermal Stability of Cubic-Phase CsPbI3 Quantum Dots.
AB  - Cubic-phase CsPbI3 quantum dots (QDs) have been recently synthesized with merits
      of excellent optoelectronic performance. However, vital properties of cubic
      CsPbI3 including lattice dynamics and stability at high temperature remain poorly
      explored. We fabricate cubic CsPbI3 QDs and study their lattice dynamic and
      thermal stability to 700 K. We obtain Raman modes of cubic CsPbI3 QDs from 300 to
      500 K at ultra-low-frequency range down to 15 cm-1, consistent with first
      principles calculations. Above 550 K, the modification of Raman features suggests
      sample degradation. Consistently, temperature-dependent photoluminescence
      measurements indicate the absence of other luminescence phases up to 700 K. With
      increasing temperature, the CsPbI3 QD photoluminescence peak has a blue shift
      with exponentially decreasing intensity, showing faster electronic degradation
      than structural degradation. Our work provides detailed investigation of CsPbI3
      QD lattice dynamics, band gap, and their high-temperature behavior, potentially
      useful for their emerging optoelectronic applications.

PMID- 30107129
TI  - Modular Access to Chiral 2,3-Dihydrofurans and 3,4-Dihydro-2 H-pyrans by
      Stereospecific Activation of Formylcyclopropanes through Combination of
      Organocatalytic Reductive Coupling and Lewis-Acid-Catalyzed Annulative Ring
      Opening Reactions.
AB  - An organocatalytic reductive coupling and Lewis-acid-catalyzed annulative ring
      opening strategy is developed as a two-step protocol for the stereoselective
      synthesis of dihydropyrans as the major products from the chiral
      formylcyclopropanes, CH acids, and Hantzsch ester. It is an efficient, catalytic,
      two-step protocol for the chiral synthesis of dihydropyrans and dihydrofurans.
      Structurally important and challenging functionally rich cyclopropanes containing
      cyclic-1,3-diones were synthesized in very good yields with excellent chemo-,
      enantio-, and diastereoselectivities from the readily available starting
      materials, chiral formylcyclopropanes, cyclic-1,3-diones, or CH acids and
      Hantzsch ester through an organocatalytic reductive coupling reaction at ambient
      conditions, especially without harming the cyclopropane ring. Chiral
      cyclopropanes containing cyclic-1,3-diones were stereospecifically transformed
      into dihydropyrans and dihydrofurans found in many bioactive natural products and
      drugs through an annulative ring-opening reaction by using Lewis-acid (BF3.OEt2)
      or cesium carbonate (Cs2CO3) catalysis. Highly diastereo- and regioselective ring
      opening of cyclopropanes was explained through a stereospecific intimate ion pair
      pathway.

PMID- 30107130
TI  - Trap-Limited Dynamics of Excited Carriers and Interpretation of the
      Photoluminescence Decay Kinetics in Metal Halide Perovskites.
AB  - Interpretation of the photoluminescence (PL) decay kinetics in metal halide
      perovskites (MHPs) is extremely important for understanding the mechanisms and
      control of charge recombination in these promising photovoltaic and
      optoelectronic materials. In this work, we give a review of current models
      describing the PL decay kinetics in MHP layers and nanocrystals with particular
      attention to the interpretation of long-lived PL decay components (hundreds of
      nanoseconds to microseconds). First, we analyze phenomenological photophysical
      models based on the rate equations, which describe the charge carrier
      recombination in MHP layers as an exclusively intrinsic bulk process. An
      important role of the carrier diffusion and nonradiative recombination on the
      layer surfaces is then discussed. A recently published approach is then analyzed,
      in the framework of which the observed long-lived components of PL decay kinetics
      in MHP nanocrystals are described in terms of the delayed luminescence mechanism
      arising due to the processes of multiple trapping and detrapping of carriers by
      shallow nonquenching traps. The possible origin of the shallow traps and
      perspectives to include the carrier trapping and detrapping processes in a model
      describing PL kinetics in MHP layers are discussed.

PMID- 30107131
TI  - Plasmon Controlled Shaping of Metal Nanoparticle Aggregates by Femtosecond Laser
      Induced Melting.
AB  - In this work, we show how to control the morphology of femtosecond laser melted
      gold nanosphere aggregates. A careful choice of both laser fluence and wavelength
      makes it possible to selectively excite different aggregate substructures to
      produce larger spherical nanoparticles, nanorods, and nanoprisms or necklace-like
      1D nanostructures in which the nanoparticles are interlinked by bridges. Finite
      integral technique calculations have been performed on the near-field
      concentration of light in the nanostructures which confirm the wavelength
      dependence of the light concentration and suggest that the resulting localized
      high intensities lead to nonthermal melting. We show that by tuning the
      wavelength of the melting light it is possible to choose the spatial extension of
      the ensembles of NPs heated thus allowing us to exhibit control over the
      morphology of the nanostructures formed by the melting process. By a proper
      combination of this method with self-assembly of chemically synthesized
      nanoparticles, one can envisage the development of an innovative high-throughput
      high-resolution nanofabrication technique.

PMID- 30107132
TI  - Environmentally and Mechanically Stable Selenium 1D/2D Hybrid Structures for
      Broad-Range Photoresponse from Ultraviolet to Infrared Wavelengths.
AB  - Selenium (Se) is one of the potential candidates as photodetector because of its
      outstanding properties such as high photoconductivity (~8 * 104 S cm-1),
      piezoelectricity, thermoelectricity, and nonlinear optical responses. Solution
      phase synthesis becomes an efficient way to produce Se, but a contamination issue
      that could deteriorate the electric characteristic of Se should be taken into
      account. In this work, a facile, controllable approach of synthesizing Se
      nanowires (NWs)/films via a plasma-assisted growth process was demonstrated at
      the low substrate temperature of 100  degrees C. The detailed formation
      mechanisms of nanowires arrays to thin films at different plasma powers were
      investigated. Moreover, indium (In) layer was used to enhance the adhesive
      strength with 50% improvement on a SiO2/Si substrate by mechanical interlocking
      and surface alloying between Se and In layers, indicating great tolerance for
      mechanical stress for future wearable devices applications. Furthermore, the
      direct growth of Se NWs/films on a poly(ethylene terephthalate) substrate was
      demonstrated, exhibiting a visible to broad infrared detection ranges from 405 to
      1555 nm with a high on/off ratio of ~700 as well as the fast response time less
      than 25 ms. In addition, the devices exhibited fascinating stability in the
      atmosphere over one month.

PMID- 30107133
TI  - Unraveling Kinetically-Driven Mechanisms of Gold Nanocrystal Shape
      Transformations Using Graphene Liquid Cell Electron Microscopy.
AB  - Mechanisms of kinetically driven nanocrystal shape transformations were
      elucidated by monitoring single particle etching of gold nanocrystals using in
      situ graphene liquid cell transmission electron microscopy (TEM). By
      systematically changing the chemical potential of the oxidative etching and then
      quantifying the facets of the nanocrystals, nonequilibrium processes of atom
      removal could be deduced. Etching at sufficiently high oxidation potentials, both
      cube and rhombic dodecahedra (RDD)-shaped gold nanocrystals transform into
      kinetically stable tetrahexahedra (THH)-shaped particles. Whereas {100}-faceted
      cubes adopt an { hk0}-faceted THH intermediate where h/ k depends on chemical
      potential, {110}-faceted RDD adopt a {210}-faceted THH intermediate regardless of
      driving force. For cube reactions, Monte Carlo simulations show that removing 6
      coordinate edge atoms immediately reveals 7-coordinate interior atoms. The rate
      at which these 6- and 7-coordinate atoms are etched is sensitive to the chemical
      potential, resulting in different THH facet structures with varying driving
      force. Conversely, when RDD are etched to THH, removal of 6-coordinate edge atoms
      reveals 6-coordinate interior atoms. Thus, changing the driving force for
      oxidation does not change the probability of edge atom versus interior atom
      removal, leading to a negligible effect on the kinetically stabilized
      intermediate shape. These fundamental insights, facilitated by single-particle
      liquid-phase TEM imaging, provide important atomic-scale mechanistic details
      regarding the role of kinetics and chemical driving force in dictating shape
      transformations at the nanometer length scale.

PMID- 30107134
TI  - Glucocorticoid-induced TNFR-related gene (GITR) as a therapeutic target for
      immunotherapy.
AB  - INTRODUCTION: Triggering of the glucocorticoid-induced TNFR-related gene (GITR)
      increases the activation of T lymphocytes and other immune system cells;
      furthermore, its ligand, GITRL, delivers signals in the cells where it is
      expressed. Areas covered: This review describes the effects of GITR/GITRL
      triggering/inhibition in conventional T cells, regulatory T cells (Tregs),
      monocytes/macrophages, endothelial cells and other cells of the immune system.
      GITR triggering appears to be an approach for promoting tumor rejection, treating
      infection and boosting vaccinations in several murine models. GITR inhibition may
      be useful for inhibiting inflammation and autoimmune disease development. Expert
      opinion: The exciting antitumor activity of anti-GITR mAbs depends on CD8+
      effector T cell activation and inhibition/deletion of tumor-infiltrating Tregs.
      Whether one of these effects is more relevant is still under debate. Inhibition
      of GITR triggering plays an interesting anti-inflammatory role, but the potential
      effect of long-term treatment is to be investigated. The use of adjuvants able to
      trigger GITR is promising regarding new vaccines. Finally, caution is recommended
      when translating the findings of experimental murine models to human diseases;
      biologicals modulating human GITR/GITRL system can behave differently from those
      modulating the murine GITR/GITRL system.

PMID- 30107135
TI  - High Fat Diet Leads to Adiposity and Adipose Tissue Inflammation: The Effect of
      Whey Protein Supplementation and Aerobic Exercise Training.
AB  - There is little understanding about dietary proteins and their potential
      contribution to obesity-induced inflammation. This study investigates the effect
      of 10 weeks of aerobic training and whey protein (WP) supplementation on visceral
      adipose tissue inflammation in rats fed a high fat diet (HFD). In the first
      phase, 40 male Wistar rats were randomly divided into two groups: 1- normal diet
      (n=8), 2- high-fat diet (n=32). After this period-which lasted nine weeks-in the
      second phase, rats fed a HFD were randomly assigned into four groups:
      (n=8/group): 1- sedentary, 2- WP, 3- aerobic training, and 4- WP + aerobic
      training. The aerobic training was performed for 10 weeks, five days/week at 21
      m/min, 15% incline, 60 minutes/day. HFD significantly increased body weight,
      adiposity index, fat pads weight, glucose levels, and insulin resistance index
      compared to the normal diet. Also, levels of TNF-alpha, MCP-1, HIF-1alpha, and
      VEGF-A in adipose tissue and serum levels of TNF-alpha were increased in the HFD
      group. Glucose levels, insulin resistance index, and triglyceride (TG) were
      reduced only by WP, independently of aerobic training. Both the aerobic training
      and WP reduced the fat pads weight, levels of TNF-alpha, HIF-1alpha, and VEGF-A
      in adipose tissue. Nevertheless, the levels of MCP-1 in adipose tissue and serum
      levels of TNF- alpha and MCP-1 were not reduced significantly by WP or aerobic
      training. These findings suggest that both aerobic training and WP
      supplementation lead to a reduction in adiposity and ameliorate obesity-induced
      inflammation in visceral adipose tissue.

PMID- 30107136
TI  - A patent review on PD-1/PD-L1 antagonists: small molecules, peptides, and
      macrocycles (2015-2018).
AB  - INTRODUCTION: The protein-protein interaction PD1/PD-L1 is an important immune
      checkpoint and several recently approved monoclonal antibodies show promising
      anti cancer activities in the clinical practice. However, only a small percentage
      of cancer patients benefit from PD1/PD-L1 directed mAbs. Moreover, some patients
      experience immune related side effects upon treatment with these mAbs. Recently,
      several atomic-resolution structures of human PD1/PD-L1, and small molecules,
      peptides and mAbs with PD-L1 and PD1 open the field for structure based drug
      design. Small molecules and peptides targeting PD1/PD-L1 promise to enhance tumor
      activity while showing less immune related side effects. Areas covered: We
      reviewed the small molecules classes and peptides targeting PD1/PD-L1. Expert
      opinion: Currently approved PD1/PD-L1 directed therapeutics show room for
      improvement. Three classes of non mAb small molecule classes have been discovered
      so far: (cyclic) peptides as direct competitive PD1/PD-L1 antagonists; small
      molecules disrupting PD1/PD-L1 and inducing a PD-L1 dimerization; and a small
      molecule class of unknown mode-of-action. An example of the later group CA-170 is
      currently investigated in a Phase 1 trial in patients with advanced solid tumors
      and lymphomas. Potential advantages of small molecules over mAbs include high
      distribution and better tumor penetration, improved PK/PD, less side effects and
      oral bioavailability.

PMID- 30107137
TI  - N-acetyl-l-cysteine attenuates oxidative damage and neurodegeneration in rat
      brain during aging.
AB  - N-acetyl-l-cysteine (NAC) is a precursor of cysteine, which is known to increase
      the level of glutathione (GSH) in the brain. Several neurodegenerative changes
      linked to oxidative stress take place in the aging brain. This study aimed to
      assess the neuroprotective effect of NAC supplementation on age-dependent
      neurodegeneration in the rat brain. Young (4 months) and old (24 months) Wistar
      rats (n = 6 rats/group) were supplemented with NAC (100 mg/kg b.w. orally) for 14
      days. Enzymatic and nonenzymatic antioxidants such as superoxide dismutase and
      catalase, and GSH and total thiol respectively, prooxidants such as protein
      carbonyl, advanced oxidation protein products, reactive oxygen species, and
      malondialdehyde were assessed in the brain homogenates. Furthermore, nitric oxide
      level, acetylcholinesterase activity, and Na+/K+-ATPase activity were measured
      and gene expression studies were also performed. The results indicated that NAC
      augmented the level of enzymatic and nonenzymatic antioxidants with a significant
      reduction in prooxidant levels in old rats. NAC supplementation also
      downregulated the expression of inflammatory markers (TNF-alpha, IL-1beta, IL-6)
      and upregulated the expression of marker genes associated with aging (sirtuin-1)
      and neurodegeneration (neuron-specific enolase, neuroglobin, synapsin-I, myelin
      basic protein 2) in old rats. The present findings support a neuroprotective role
      of NAC which has therapeutic implication in controlling age-related neurological
      disorders.

PMID- 30107139
TI  - Intimate-partner violence and reproductive decision-making by women attending
      Victorian Maternal- and Child-Health services: a cross-sectional study.
AB  - The reproductive years are a critical period where women experience greater risk
      of intimate-partner violence (IPV). Most studies investigating the association
      between IPV and reproductive health have been completed in low- and middle-income
      countries. This study aimed to examine the relationship between IPV and women's
      reproductive decision-making in Victoria, Australia. We analysed secondary data
      from a cluster-randomised trial of IPV screening that surveyed new mothers
      attending Maternal- and Child-Health centres in Melbourne. Survey measures
      included the experience of partner abuse in the past 12 months using the
      Composite Abuse Scale and four reproductive decision-making indicators. Results
      showed that IPV affects reproductive decision-making among postpartum women.
      Women who reported abuse were less likely to plan for a baby (adjusted Odds Ratio
      0.48, 95% CI: 0.31-0.75) than were non-abused women, significantly more likely to
      have partners make decisions for them about contraception (Risk ratio (RR) 4.09,
      95% CI: 1.31-12.75), and whether and when to have a baby (RR 12.35, 95% CI: 4.46
      34.16), than they were to make decisions jointly. Pregnant and postpartum women
      need to be screened for partner violence that compromises women's decision-making
      power regarding their reproductive rights.

PMID- 30107138
TI  - Fragile Histidine Triad (FHIT), a Novel Modifier Gene in Pulmonary Arterial
      Hypertension.
AB  - RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by progressive
      narrowing of pulmonary arteries resulting in right heart failure and death. Bone
      Morphogenetic Protein Receptor type-2 (BMPR2) mutations account for most familial
      PAH (FPAH) forms while reduced BMPR2 is present in many idiopathic PAH (IPAH)
      forms, suggesting dysfunctional BMPR2 signaling to be a key feature of PAH.
      Modulating BMPR2 signaling is therapeutically promising, yet how BMPR2 is
      downregulated in PAH is unclear. OBJECTIVES: We intended to identify and
      pharmaceutically target BMPR2 modifier genes to improve PAH. METHODS: We combined
      siRNA High Throughput Screening (HTS) of >20,000 genes with a multi-cohort
      analysis of publicly available PAH RNA expression data to identify clinically
      relevant BMPR2-modifiers. After confirming gene dysregulation in PAH patient
      tissue, we determined the functional roles of BMPR2-modifiers in vitro and tested
      the repurposed drug Enzastaurin for its propensity to improve experimental PH.
      MEASUREMENTS AND MAIN RESULTS: We discovered Fragile Histidine Triad (FHIT) as a
      novel BMPR2-modifier. BMPR2 and FHIT expression were reduced in PAH patients.
      FHIT reductions were associated with endothelial and smooth muscle cell
      dysfunction, rescued by Enzastaurin through a dual mechanism: upregulation of
      FHIT as well as miR17-5 repression. Fhit-/- mice had exaggerated hypoxic PH and
      failed to recover in normoxia. Enzastaurin reversed PH in the
      Sugen5416/Hypoxia/Normoxia rat model, by improving Right Ventricular Systolic
      Pressure (RVSP), RV hypertrophy, cardiac fibrosis and vascular remodeling.
      CONCLUSIONS: This study highlights the importance of the novel BMPR2 modifier
      FHIT in PH and the clinical value of the repurposed drug Enzastaurin as a
      potential novel therapeutic strategy to improve PAH.

PMID- 30107140
TI  - Evaluation of Aib and PEG-polymer insect kinin analogs on mosquito and tick GPCRs
      identifies potent new pest management tools with potentially enhanced
      biostability and bioavailability.
AB  - Insect kinins modulate aspects of diuresis, digestion, development, and sugar
      taste perception in tarsi and labellar sensilla in mosquitoes. They are, however,
      subject to rapid biological degradation by endogenous invertebrate peptidases. A
      series of alpha-aminoisobutyric (Aib) acid-containing insect kinin analogs
      incorporating sequences native to the Aedes aegypti mosquito aedeskinins were
      evaluated on two recombinant kinin invertebrate receptors stably expressed in
      cell lines, discovering a number of highly potent and biostable insect kinin
      mimics. On the Ae. aegypti mosquito kinin receptor, three highly potent,
      biostable Aib analogs matched the activity of the Aib-containing biostable insect
      kinin analog 1728, which previously showed disruptive and/or aversive activity in
      aphid, mosquito and kissing bug. These three analogs are IK-Aib-19
      ([Aib]FY[Aib]WGa, EC50 = 18 nM), IK-Aib-12 (pQKFY[Aib]WGa, EC50 = 23 nM) and IK
      Aib-20 ([Aib]FH[Aib]WGa, EC50 = 28 nM). On the Rhipicephalus (Boophilus)
      microplus tick receptor, IK-Aib-20 ([Aib]FH[Aib]WGa, EC50 = 2 nM) is more potent
      than 1728 by a factor of 3. Seven other potentially biostable analogs exhibited
      an EC50 range of 5-10 nM, all of which match the potency of 1728. Among the multi
      Aib hexapeptide kinin analogs tested the tick receptor has a preference for the
      positively-charged, aromatic H over the aromatic residues Y and F in the X1
      variable position ([Aib]FX1[Aib]WGa), whereas the mosquito receptor does not
      distinguish between them. In contrast, in a mono-Aib pentapeptide analog
      framework (FX1[Aib]WGa), both receptors exhibit a preference for Y over H in the
      variable position. Among analogs incorporating polyethylene glycol (PEG) polymer
      attachments at the N-terminus that can confer enhanced bioavailability and
      biostability, three matched or surpassed the potency of a positive control
      peptide. On the tick receptor IK-PEG-9 (P8-R[Aib]FF[Aib]WGa) was the most potent.
      Two others, IK-PEG-8 (P8-RFFPWGa) and IK-PEG-6 (P4-RFFPWGa), were most potent on
      the mosquito receptor, with the first surpassing the activity of the positive
      control peptide. These analogs and others in the IK-Aib series expand the toolbox
      of potent analogs accessible to invertebrate endocrinologists studying the
      structural requirements for bioactivity and the as yet unknown role of the insect
      kinins in ticks. They may contribute to the development of selective,
      environmentally friendly pest arthropod control agents.

PMID- 30107141
TI  - Reply.

PMID- 30107142
TI  - Invited Commentary.

PMID- 30107143
TI  - Reply.

PMID- 30107144
TI  - Invited Commentary.

PMID- 30107145
TI  - Reply.

PMID- 30107146
TI  - Mammalian heme peroxidases: From innate immunity to pathology and extracellular
      matrix biosynthesis.

PMID- 30107147
TI  - CCR7 preservation via histone deacetylase inhibition promotes epithelial
      mesenchymal transition of hepatocellular carcinoma cells.
AB  - The effects of Histone deacetylase (HDAC) inhibition on epithelial-mesenchymal
      transition (EMT) differs in various types of cancers. However, its function in
      hepatocellular carcinoma (HCC) is not well-explored. In this study, we
      investigated the effect of HDAC inhibition on EMT in HCC cells by using
      trichostatin A (TSA) and valproic acid (VPA). The results showed that TSA/VPA
      significantly induced EMT phenotype, as demonstrated by the decreased level of E
      cadherin, increased level of N-cadherin, vimentin, Twist and snail, and enhanced
      capacity of cell migration and invasion. In addition, CCR7 was speculated and
      confirmed as a function target of HDAC inhibition. CCR7 promotes the progression
      of HCC and is associated with poor survival. Knockdown of CCR7 significantly
      attenuated the effect of TSA on EMT. Moreover, our results demonstrated that HDAC
      inhibition up-regulates CCR7 via reversing the promoter hypoacetylation and
      increasing CCR7 transcription. Taken together, our study has identified the
      function of HDAC in EMT of HCC and suggested a novel mechanism through which
      TSA/VPA exerts its carcinogenic roles in HCC. HDAC inhibitors require careful
      caution before their application as new anticancer drugs.

PMID- 30107148
TI  - Ubiquitous parasites drive a 33% increase in methane yield from livestock.
AB  - Of anthropogenic methane emissions, 40% can be attributed to agriculture, the
      majority of which are from enteric fermentation in livestock. With international
      commitments to tackle drivers of climate change, there is a need to lower global
      methane emissions from livestock production. Gastrointestinal helminths
      (parasitic worms) are globally ubiquitous and represent one of the most pervasive
      challenges to the health and productivity of grazing livestock. These parasites
      influence a number of factors affecting methane emissions including feed
      efficiency, nutrient use, and production traits. However, their effects on
      methane emissions are unknown. This is to our knowledge the first study that
      empirically demonstrates disease-driven increases in methane (CH4) yield in
      livestock (grams of CH4 per kg of dry matter intake). We do this by measuring
      methane emissions (in respiration chambers), dry matter intake, and production
      parameters for parasitised and parasite-free lambs. This study shows that
      parasite infections in lambs can lead to a 33% increase in methane yield (g
      CH4/kg DMI). This knowledge will facilitate more accurate calculations of the
      true environmental costs of parasitism in livestock, and reveals the potential
      benefits of mitigating emission through controlling parasite burdens.

PMID- 30107149
TI  - The success of sequence capture in relation to phylogenetic distance from a
      reference genome: a case study of avian haemosporidian parasites.
AB  - Genomic sequencing of avian haemosporidian parasites (Haemosporida) has been
      challenging due to excessive contamination from host DNA. In this study, we
      developed a cost-effective protocol to obtain parasite sequences from naturally
      infected birds, based on targeted sequence capture and next generation
      sequencing. With the genomic data of Haemoproteus tartakovskyi as a reference, we
      successfully sequenced up to 1000 genes from each of the 15 selected samples
      belonging to nine different cytochrome b lineages, eight of which belong to
      Haemoproteus and one to Plasmodium. The targeted sequences were enriched to ~104
      fold, and mixed infections were identified as well as the proportions of each
      mixed lineage. We found that the total number of reads and the proportions of
      exons sequenced decreased when the parasite lineage became more divergent from
      the reference genome. For each of the samples, the recovery of sequences from
      different exons varied with the function and GC content of the exon. From the
      obtained sequences, we detected within-lineage variation in both mitochondrial
      and nuclear genes, which may be a result of local adaptation to different host
      species and environmental conditions. This targeted sequence capture protocol can
      be applied to a broader range of species and will open a new door for further
      studies on disease diagnostics and comparative analysis of haemosporidians
      evolution.

PMID- 30107150
TI  - Rabbit trypanosome detection in Phlebotomus perniciosus sand flies from the
      leishmaniasis outbreak in Madrid, Spain.
AB  - Phlebotomine sand flies are known vectors of several pathogens. In Spain,
      Phlebotomus perniciosus and Phlebotomus ariasi are the proven vectors of
      Leishmania infantum. Since 2010 a human leishmaniasis outbreak has been notified
      in Madrid region, central Spain. Studies have shown that P. perniciosus is the
      only vector confirmed in the focus area and that rabbits and hares are the wild
      reservoirs incriminated in the cycle of the parasite in the outbreak. Trypanosoma
      nabiasi is a trypanosomatid found in wild rabbits and its presence has been
      reported in wild rabbits from southern Spain. Moreover, co-infection with L.
      infantum was found in some of these animals. However, in Madrid region, there is
      no information about the transmission of this trypanosome in rabbits. Hence, in
      this study we investigate if T. nabiasi could be circulating in the
      aforementioned leishmaniasis focus. Wild P. perniciosus female sand flies were
      captured in the affected area and analyzed using molecular methods. T. nabiasi
      DNA was detected in 20 out of 155 female sand flies fed on rabbits by
      amplification and subsequent sequencing of ITS1 and SSU rRNA fragments.
      Therefore, we describe for the first time the presence of T. nabiasi and its co
      infection with L. infantum in P. perniciosus female sand flies. More
      investigation is needed in order to elucidate the role of P. perniciosus in the
      transmission of T. nabiasi among rabbits and its potential consequences.

PMID- 30107151
TI  - Morphology and 18S rDNA sequencing of Henneguya peruviensis n. sp. (Cnidaria:
      Myxosporea), a parasite of the Amazonian ornamental fish Hyphessobrycon
      loretoensis from Peru: A myxosporean dispersal approach.
AB  - Myxosporean are endoparasitic cnidarians of wide distribution and responsible for
      important economic losses in fisheries and aquaculture. A new myxosporean
      species, Henneguya peruviensis n. sp., is herein described as obtained from the
      gill filaments of Hyphessobrycon loretoensis caught in the Nanay River,
      Department of Loreto, Peru. The parasite was found in 37 of 45 (82.2%) examined
      H. loretoensis. The new species was characterized based on morphological features
      and 18S rDNA gene sequence data. The sequencing of the 18S rDNA gene from the
      spores of H. peruviensis n. sp. resulted in 1632 nucleotides and this sequence
      did not match any of the myxozoan available in the GenBank. Phylogenetic analysis
      showed that H. peruviensis n. sp. closed together with H. leporinicola.
      Nonetheless, the 18S rDNA sequences of H. peruviensis n. sp. and H. leporinicola
      have only 82% similarity. This is the first description and molecular study of a
      Myxozoa parasitizing fish of the genus Hyphessobrycon in the Amazon basin. Given
      the importance of the ornamental fish industry in translocation of aquatic
      organisms worldwide, the international movement of myxosporeans in infected fish
      is discussed in terms of disease outbreaks and the need for preventative action.

PMID- 30107152
TI  - Small benzothiazole molecule induces apoptosis and prevents metastasis through
      DNA interaction and c-MYC gene supression in diffuse-type gastric adenocarcinoma
      cell line.
AB  - Chemo-resistance has been reported as a relevant barrier for the efficiency of
      gastric cancer treatment. Therefore, the development of effective and safe drugs
      for cancer chemotherapy is still a challenge. The purpose of this study was to
      evaluate the anticancer potential of (E)-2-(((2-(benzo[d]thiazo-2
      yl)hydrazono)methyl)-4-nitrophenol) (AFN01) against gastric cancer cell lines.
      Our results showed promising anticancer activity against gastric cancer cells ACP
      02 (IC50 = 1.0 MUM) and mild activity against other cell lines including non
      malignant gastric cell MNP-01 (IC50 = 3.4 MUM). This compound significantly
      induced S phase cell cycle arrest, prevented cell migration and triggered
      apoptosis in a concentration-dependent manner. Moreover, AFN01 was significantly
      more genotoxic against tumoral cell ACP-02, when compared to non-malignant cells,
      such as MNP-01 and healthy peripheral mononuclear blood cells. AFN01 also
      synergistically interacts with doxorubicin suppressing cell proliferation and c
      MYC gene expression in gastric cancer cell line model, with remarkable c-MYC
      overexpression. Although further pre-clinical and clinical studies are required
      to explore its safety and efficiency, AFN01 may represent a promising lead
      anticancer agent for the treatment of gastric cancer.

PMID- 30107153
TI  - Protective effects of apigenin against 3-MCPD-induced renal injury in rat.
AB  - Apigenin (API) is a kind of important flavonoid present in temperate and tropical
      fruit and vegetables, especially the celery. It exerts anticancer, anti
      bacterial, anti-viral, anti-inflammatory, anti-oxidation properties. In the
      present study, the mechanism of protective action of apigenin on 3-chloro-1, 2
      propanediol (3-MCPD)-induced renal injury was investigated in rat. Sprague-Dawley
      (SD) rats were divided into five groups: control group (ultrapure water treated),
      CMC group (sodium carboxymethylcellulose treated), 3-MCPD treatment group (30
      mg/kg body weight/day), 3-MCPD plus API co-treatment group (20, 40 mg/kg body
      weight/day). The results showed that API significantly reduced renal function
      markers, serum creatinine and urea nitrogen content. Besides, the renal tissue
      lesion in 3-MCPD treatment group was restored by API to some extent. We indicated
      that API exerted renoprotective effect by modulating oxidative phosphorylation
      especially up-regulated the expressions of ATP6 and ATP8, re-establishing
      mitochondrial membrane potential (MMP), relieving the increase of Bax/Bcl2 ratio,
      reducing cytochrome c release, thus inhibiting the activation of Caspase 9 and
      Caspase 3. In conclusion, apigenin possesses excellent protective effect against
      3-MCPD-induced renal injury by modulating mitochondria dependent Caspase cascade
      pathway.

PMID- 30107155
TI  - Modulating the excitability of the visual cortex using a stimulation priming
      paradigm.
AB  - BACKGROUND: Transcranial random noise stimulation (tRNS) can cause long term
      increase of corticospinal excitability when used to prime the motor cortex,
      before measuring the motor response in the hand muscles with TMS (Terney et al.,
      2008). In cognitive studies, tRNS has been used to improve visual attention and
      mathematical skills, an enhancement effect that might suggest sustained cortical
      plasticity changes (Cappelletti et al., 2013; Snowball et al., 2013). However,
      while the behavioral evidence of increased performance is becoming substantiated
      by empirical data, it still remains unclear whether tRNS over visual areas causes
      an increase in cortical excitability similar to what has been found in the motor
      cortex, and if that increase could be a potential physiological explanation for
      behavioral improvements found in visual tasks. OBJECTIVE/HYPOTHESIS: In the
      present study, we aimed to investigate whether priming the visual cortex with
      tRNS leads to increased and sustained excitability as measured with visual
      phosphenes. METHODS: We measured phosphene thresholds (PTs) using an objective
      staircase method to quantify the magnitude of cortical excitability changes.
      Single-pulse TMS was used to elicit phosphenes before, immediately after, and
      every 10 min up to one hour after the end of 20 min tRNS, anodal tDCS (a-tDCS) or
      sham. RESULTS: Results showed that phosphene thresholds were significantly
      reduced up to 60 min post stimulation relative to baseline after tRNS, a
      behavioral marker of increased excitability of the visual cortex, while a-tDCS
      had no effect. This result is very similar in magnitude and duration to what has
      been found in the motor cortex. CONCLUSIONS: Our findings demonstrate promising
      potential of tRNS as a tool to increase and sustain cortical excitability to
      promote improvement of cognitive functions.

PMID- 30107156
TI  - Macrophage depletion by clodronate attenuates bone morphogenetic protein-7
      induced M2 macrophage differentiation and improved systolic blood velocity in
      atherosclerosis.
AB  - Bone morphogenetic protein-7 (BMP-7) affects the presence of macrophage subtypes
      in vitro and in vivo at an early stage of atherosclerosis (ATH); however, it
      remains unknown whether BMP-7 treatment affects the development and progression
      of ATH at a mid-stage of the disease. We therefore performed a Day 28 (D28) study
      to examine BMP-7's potential to affect monocyte differentiation. Atherosclerosis
      was developed in ApoE KO mice, and these animals were treated with intravenous
      injections of BMP-7 and/or liposomal clodronate (LC). BMP-7 significantly (P <
      0.05) lowers plaque formation following induction of atherosclerosis. However,
      upon macrophage depletion, BMP-7 fails to significantly alter plaque progression
      suggesting a direct role of BMP-7 on macrophages. Immunohistochemical staining of
      carotid arteries was performed to determine BMP-7's effect on pro-inflammatory M1
      inducible nitric oxide synthase and anti-inflammatory M2 (cluster of
      differentiation [CD]206, Arginase-1) macrophages, and monocytes ( CD14). BMP-7
      significantly reduced pro-inflammatory M1 macrophages and increased anti
      inflammatory M2 macrophages at D28, while BMP-7 showed no effect on M2 macrophage
      differentiation in animals treated with LC. Enzyme-linked immunosorbent assay
      data showed significant reduction in proinflammatory cytokines (Interleukin-6 [IL
      6]), monocyte chemoattractant protein-1, and tumor necrosis factor-alpha) and a
      significant increase in anti-inflammatory cytokine (IL-10) in BMP-7 treated mice
      (P < 0.05).Western blot analysis of arterial tissue confirms a significant
      increase in pro-survival kinases extracellular-signal regulated kinase and SMAD
      and a reduction in pro-inflammatory kinases p38 and c-Jun N-terminal kinase in
      BMP-7 treated mice (P < 0.05). Overall, this study suggests that clodronate
      treatment inhibits BMP-7 induced differentiation of monocytes into M2 macrophages
      and improved systolic blood velocity.

PMID- 30107157
TI  - Synthesis and purification of linkage-specific polyubiquitin chains of distinct
      length for structural studies.
AB  - Polyubiquitylation is one of the most versatile post-translational modifications
      involved in the regulation of numerous intracellular signaling processes. An
      assembly procedure that is simple, robust, and efficient to synthesize and purify
      linkage-specific polyubiquitin chains of defined length at a preparative scale is
      required in biophysical and structural studies. Here, we have optimized known
      enzymatic procedures in the form of a protocol to obtain multi-milligrams of
      Lys48-and Lys63-linked polyubiquitin chain types with more than 99% purity. Mass
      spectrometry (ESI/MS) analysis of K48- and K63-linked diubiquitin confirmed that
      the enzymes used in the preparation generated homogeneous linkages with no
      promiscuity.

PMID- 30107154
TI  - Human cryptosporidiosis in immunodeficient patients in France (2015-2017).
AB  - Cryptosporidiosis is a common disease in children and immunodeficient
      individuals. In 2006, a national network was set up on the surveillance of human
      cryptosporidiosis in France. Since January 2015, the 41 tertiary care hospitals
      and the 3 private laboratories of the French National Network on the surveillance
      of human cryptosporidiosis have been able to declare confirmed cases of
      cryptosporidiosis online. Between 2015 and 2017, 210 cases of cryptosporidiosis
      were declared in immunodeficient patients in France; Cryptosporidium parvum and
      Cryptosporidium hominis represented 66% and 22% of cases, respectively. A peak
      was observed in autumn. Cryptosporidiosis occurred mainly in a context of solid
      organ transplantation (SOT) (49%) and of HIV infection (30%). In SOT recipients,
      cryptosporidiosis appeared more frequently in the first 6 months post
      transplantation. Regarding cases declared in SOT recipients, mycophenolate
      mofetil was used in 68%. A mortality rate of 6% was observed. Present results
      underline the importance of screening for cryptosporidiosis in immunocompromised
      patients suffering from diarrhea, especially in the course of major cell mediated
      immunodeficiency or even systematic screening before SOT. Exclusive
      Cryptosporidium free water feeding could be suggested during major cell mediated
      immunodeficiency.

PMID- 30107158
TI  - Culture characters, genetic background, estrogen/progesterone receptor
      expression, and tumorigenic activities of frequently used sixteen endometrial
      cancer cell lines.
AB  - BACKGROUND: This study aimed to determine the in vitro and in vivo properties of
      sixteen frequently used endometrial cancer (EC) cell lines, including the cell
      proliferation rate, morphology, hormone receptor expression patterns, PTEN, hMLH1
      expression, p53 mutation, karyotype, and tumorigenicity in mouse xenograt model.
      METHODS: Twelve type I (AN3, ECC-1, EN, EN-1, EN-11, HEC-1A, HEC1B, Ishikawa,
      KLE, MFE-280, MFE-296, MFE-319) and four type II (ARK1, ARK2, HEC-155/180, SPEC
      2) endometrial cancer cell lines were studied. Cell proliferation and morphology
      were determined using cell growth curves and light microscopy, respectively. Real
      time PCR was performed to measure the mRNA levels of target genes. Denaturing
      High Performance Chromatography (DHPLC) screening and PCR/sequencing were
      performed to identify p53 mutations. G-banding was applied for karyotyping.
      Tumorigenicity was evaluated using mouse xenograft. RESULTS: The population
      doubling time of the cell lines ranged between 19 and 41 h. Ishikawa, ECC-1, and
      MFE-280 have high while AN3 and EN1 have low expression of ER-alpha and ER-beta.
      Expression of total PR and PR-B uniformly decreased in all type II cell lines and
      several type I cell lines (AN3, HEC-1A, HEC1B, KLE, EN-1). Regression analyses
      revealed significant correlations between PR-B and total PR (p < .001), between
      isoforms ER-alpha and ER-beta (p < .001), and between total PR and ER (p < .001),
      mRNA levels in type I cell lines. p53 mutations were detected in exons 5-8 of
      seven out of twelve type I and one out of four type II cell lines. PTEN
      expression was more uniformly suppressed in type II than type I cells, while
      hMLH1 did not show this pattern. All the five cell lines tested contained severe
      karyotype abnormalities. Mouse xenograft results indicated that HEC-1A, HEC-1B
      and EN-1 type I as well as ARK1 and ARK2 type II cell lines had potent
      tumorigenic activities. Low PR-B and ER-alpha expression in type I cell lines
      were associated with high tumorigenic activity. CONCLUSIONS: This study provides
      resource information on EC cell lines commonly used in laboratories, which could
      be used for choosing cell lines suitable for specific research purposes. The
      results of karyotype analysis and p53 mutation together with hormone receptor
      expression pattern and morphology comparison strongly suggested an independent
      nature of these cell lines, excluding the possibility of cross-contamination
      between cell lines. Additionally, this information suggests potential directions
      for future studies on the pathogenic mechanisms of endometrial cancer.

PMID- 30107159
TI  - Evolution of coeloconic sensilla in the peripheral olfactory system of Drosophila
      mojavensis.
AB  - Populations inhabiting habitats with different environmental conditions, such as
      climate, resource availability, predation, competition, can undergo selection for
      traits that are adaptive in one habitat and not the other, leading to divergence
      between populations. Changes in the olfactory systems of insects that rely on
      different host plants, for example, can occur in response to differences in
      sensory stimuli between habitats. In this study, we investigate the evolution of
      host preference by characterizing the coeloconic sensilla in Drosophila
      mojavensis, a species that breeds on different necrotic cacti across its
      geographic range. These cactus species differ in the volatile chemicals they
      emit, a primary sensory cue for host plant discrimination. Analysis of odor
      evoked responses identified four coeloconic sensilla that were qualitatively
      similar to those of Drosophila melanogaster, but varied in the breadth and
      strength of their olfactory sensory neuron responses to some acids and amines.
      Variation in responses to certain odorants among D. mojavensis populations was
      also observed. Compared to D. melanogaster, there was a lack of sensitivity of
      antennal coeloconic type 3 (ac3) sensilla to primary ligands of OR35a across all
      populations. Consistent with this result was a lack of detectable Or35a gene
      expression. Using a comparative approach, we then examined odor specificity of
      ac3 sensilla for seven additional Drosophila species, and found that OR35a-like
      sensitivity may be limited to the melanogaster subgroup. The variation in
      specificity that was observed among species is not clearly attributable to the
      degree of ecological specialization, nor to the ecological niche.

PMID- 30107160
TI  - A novel GH16 beta-agarase isolated from a marine bacterium, Microbulbifer sp. BN3
      and its characterization and high-level expression in Pichia pastoris.
AB  - An agar-degrading bacterium, strain BN3, was isolated from a coastal soil sample
      collected in Taiwan Strait, China and identified to be a novel species of the
      genus Microbulbifer. The gene (N3-1) encoding for a novel beta-agarase from the
      isolate was cloned and sequenced. It encoded a mature protein with 274 amino
      acids and a calculated molecular mass of 34.3 kDa. The deduced amino acid
      sequence manifested sequence similarity (61-84% identity) to characterized beta
      agarases in the glycoside hydrolase family 16. The recombinant agarase was hyper
      produced extracellularly using Pichia pastoris as the host. After induction in a
      shake flask for 96 h, the yield of recombinant N3-1 protein reached 0.406 mg/mL,
      and the enzyme activity attained 502.1 U/mL. The enzyme purified by ion exchange
      chromatography displayed a specific activity of 6447 U/mg at pH 6.0 and 50 
      degrees C. The optimal pH and temperature for agarase activity were approximately
      6 and 50  degrees C, respectively. The pattern of agarose hydrolysis showed that
      the enzyme was an endo-type beta-agarase, capable of hydrolyzing agarose and
      Gracilaria lemaneiformis, with neoagarobiose and neoagarotetraose as the final
      main products.

PMID- 30107161
TI  - Bone tissue engineering: Scaffold preparation using chitosan and other
      biomaterials with different design and fabrication techniques.
AB  - In the recent years, a paradigm shift is taking place where metallic/synthetic
      implants and tissue grafts are being replaced by tissue engineering approach. A
      well designed three-dimensional scaffold is one of the fundamental tools to guide
      tissue formation in vitro and in vivo. Bone is a highly dynamic and an
      integrative tissue, and thus enormous efforts have been invested in bone tissue
      engineering to design a highly porous scaffold which plays a critical role in
      guiding bone growth and regeneration. Numerous techniques have been developed to
      fabricate highly interconnected, porous scaffold for bone tissue engineering
      applications with the help of biomolecules such as chitosan, collagen, gelatin,
      silk, etc. We aim, in this review, to provide an overview of different types of
      fabrication techniques for scaffold preparation in bone tissue engineering using
      biological macromolecules.

PMID- 30107162
TI  - Papillary Thyroid Carcinoma Incidentally Found in Cervical Lymph Nodes During
      Neck Dissection for Patients With Tongue Squamous Cell Carcinoma: A 3-Case Report
      and Literature Review.
AB  - The incidence of papillary thyroid carcinoma (PTC) found in the cervical lymph
      nodes during neck dissection for patients with tongue squamous cell carcinoma
      (SCC) is infrequent, with the coexistence of PTC and SCC in the same cervical
      lymph node being the rarest. Some of these patients present with primary lesions
      in the thyroid gland, whereas others have no obviously malignant thyroid lesion.
      The reasons behind this clinical phenomenon and the relationship between tongue
      SCC and PTC found in the cervical lymph nodes are unclear. Moreover, for
      surgeons, making the choice between thyroid surgery and follow-up is still a
      clinical dilemma. Of the 956 patients who underwent neck dissection owing to
      maxillofacial tumors from January 2011 through December 2017 at Second Xiangya
      Hospital of Central South University, 3 with tongue SCC presented with PTC in the
      cervical lymph nodes. Neither the preoperative physical examination nor
      ultrasonography after surgery showed substantial nodules in the thyroid glands of
      these patients, so none of them underwent thyroid surgery or chemoradiotherapy.
      At follow-up (1 to 6.5 years), we found no obviously malignant lesions in the
      patients' thyroid glands or related metastatic disease. Our study suggests that
      tongue SCC may not affect the occurrence and development of PTC in the cervical
      lymph nodes. For patients with tongue SCC presenting with PTC in the cervical
      lymph nodes, it is not necessary to carry out thyroid surgery immediately if
      ultrasonography shows no substantially malignant lesion in the thyroid gland.
      Nevertheless, conducting periodic follow-up is very important.

PMID- 30107163
TI  - Prostaglandin D2 evokes potent uterine contraction via the F prostanoid receptor
      in postpartum rats.
AB  - Prostaglandin (PG) D2, a prostanoid known to have hypotensive effect, can evoke
      increased in vitro prepartum myometrial contraction resulting from up-regulation
      of the F prostanoid (FP) receptor. The present study further determined
      postpartum rat uterine responses to PGD2 to evaluate the possibility of the
      prostanoid becoming a therapeutic for postpartum uterine atony, a major cause of
      postpartum hemorrhage that can lead to maternal morbidity. In vitro and in vivo
      postpartum uterine responses to PGD2 were determined and compared to those of
      prepartum rats. Here we show that in postpartum myometrial strips PGD2 did evoke
      a contraction sensitive to FP receptor antagonism. Interestingly, this response
      was not only to a greater extent than that of prepartum rats, but also comparable
      with the contraction obtained with PGF2alpha, a therapeutic for postpartum
      uterine atony but contradicted in conditions including hypertension. Indeed, PGD2
      was also found to cause increases of basal uterine contraction under in vivo
      conditions. Western blots revealed that the expression of FP receptors in
      postpartum myometrium was higher than that of prepartum rats. Moreover, we noted
      that the amount of PGD2 produced in postpartum uteri, although lower than that of
      prepartum rats, was increased compared to non-pregnant conditions. These results
      thus demonstrate that due to a further up-regulation or high expression of
      myometrial FP receptors, PGD2 can evoke potent uterine contraction postpartum,
      and hence the prostanoid, which is naturally synthesized in uterine tissues,
      could be a potential therapeutic for postpartum uterine atony, especially in
      settings, such as hypertension.

PMID- 30107164
TI  - Suppression of TLR4 activation by resveratrol is associated with STAT3 and Akt
      inhibition in oxidized low-density lipoprotein-activated platelets.
AB  - Resveratrol has many beneficial biological actions, including cardiovascular
      protection and antithrombotic effects. Whether resveratrol inhibits oxidized low
      density lipoprotein (ox-LDL)-induced Toll-like receptor 4 (TLR4) expression in
      activated platelets remains unclear. The present study investigated the effects
      of resveratrol on the TLR4-mediated inflammatory response in ox-LDL-activated
      platelets. The results showed that resveratrol suppressed TLR4 expression in ox
      LDL- and lipopolysaccharide (LPS)-activated platelets. Similar effects were found
      in puromycin-pretreated platelets. This suggests that TLR4 expression might be
      related to protein synthesis in ox-LDL- and LPS-activated platelets. Further
      analysis confirmed that resveratrol attenuated the ox-LDL-induced phosphorylation
      of nuclear factor kappaB (NF-kappaB) and signal transducer and activator of
      transcription 3 (STAT3). A mechanistic analysis indicated that the inhibitory
      effect of resveratrol on TLR4 expression was associated with the suppression of
      Akt phosphorylation. The combination of resveratrol and the PI3K inhibitor
      LY294002 had a synergistic effect on the inhibition of Akt phosphorylation and
      TLR4 expression. Moreover, resveratrol recovered sirtuin 1 expression and
      adenosine monophosphate-activated protein kinase phosphorylation, which was
      reduced by ox-LDL treatment. Furthermore, the platelet function analysis showed
      that resveratrol (100 MUM) reduced platelet aggregation and adhesion and CD40
      ligand/platelet factor 4 secretion in ox-LDL-treated platelets. Altogether, the
      present findings show that resveratrol inhibits the TLR4-mediated inflammatory
      response in ox-LDL-activated platelets, which may contribute to the treatment of
      thrombosis and atherosclerosis.

PMID- 30107165
TI  - MiR-182 alleviates the development of cyanotic congenital heart disease by
      suppressing HES1.
AB  - miRNAs have been pointed to play critical roles in the protection and development
      of cyanotic congenital heart disease (CHD). MiR-182 is found to be associated
      with multiple heart diseases. However, little is known about the function and
      underlying mechanisms of miR-182 on cyanotic CHD. Here, H9c2 cells were exposed
      to hypoxia to construct the model of cyanotic CHD in vitro. qRT-PCR assay
      revealed that miR-182 expression was downregulated in serum samples from patients
      with cyanotic CHD and hypoxia-induced cardiomyocytes. Gain- and loss-of-function
      demonstrated that miR-182 overexpression promoted cell proliferation and
      suppressed apoptosis in hypoxia-induced H9c2 cells, while miR-182 knockdown
      repressed cell proliferation and promoted apoptosis. Dual-luciferase reporter
      assay verified that HES1 was a direct target of miR-182, and miR-182 repressed
      HES1 expression by binding to its 3'-UTR. Moreover, miR-182-mediated regulatory
      effect on cell proliferation and apoptosis was reversed by the restoration of
      HES1 expression. In conclusion, our study demonstrated that miR-182 exerted
      protection effect through suppressing HES1 in hypoxia-induced cardiomyocytes,
      highlighting its role as a potential therapeutic strategy for cyanotic CHD.

PMID- 30107166
TI  - Luteolin induces caspase-dependent apoptosis via inhibiting the AKT/osteopontin
      pathway in human hepatocellular carcinoma SK-Hep-1 cells.
AB  - AIMS: Luteolin, a naturally occurring flavonoid, possesses anti-cancer effects
      including induction of apoptosis. This study investigated the involvement of
      osteopontin (OPN) in luteolin-induced apoptosis in human hepatocellular carcinoma
      (HCC) SK-Hep-1 cells with high OPN expression. MAIN METHODS: MTT assay was used
      to determine the cell viability. Cell cycle analysis was performed to identify
      apoptosis. Apoptosis was confirmed by detecting cytoplasmic histone-associated
      DNA-fragments using a cell death detection ELISAPLUS kit. The expression of
      proteins was evaluated by Western blot. Reverse transcriptase-polymerase chain
      reaction was employed to detect the expression of mRNA. KEY FINDINGS: Cytotoxic
      effect of luteolin was higher in cancer cell line SK-Hep-1 cells than in normal
      cell line AML12 cells. Luteolin led a significantly increase in apoptosis
      accompanied by activation of caspase 8, -9 and -3 and cleavage of poly (ADP
      ribose) polymerase (PARP), which was completely blocked by Z-VAD-FMK, a pan
      caspase inhibitor. Luteolin significantly downregulated the expression of X
      linked inhibitor of apoptosis (XIAP), Mcl-1 and Bid. Furthermore, luteolin
      effectively decreased OPN expression at both mRNA and protein level. Exogenous
      OPN markedly blocked apoptosis induction, caspases activation, PARP cleavage,
      downregulation of XIAP and Mcl-1 in luteolin-treated cells. Luteolin impaired the
      AKT pathway by inhibiting the phosphorylation of AKT. SC79, an AKT activator,
      blocked apoptosis induction, caspases activation, PARP cleavage, downregulation
      of OPN, XIAP, Mcl-1 and Bid in luteolin-treated cells. SIGNIFICANCE: These
      results demonstrated that luteolin inhibits the AKT/OPN pathway, thereby inducing
      caspase-dependent apoptosis in human HCC SK-Hep-1 cells with little toxicity.

PMID- 30107168
TI  - The role of cathepsin B in autophagy during obesity: A systematic review.
AB  - White adipose tissue (WAT) regulates energy homeostasis by releasing adipokines
      and modulating cell maintenance. Nutrient excess affects adipocyte hypertrophy
      directly in WAT by increasing excessively the activity of autophagy systems,
      generating proinflammatory markers and increasing infiltration of macrophages,
      causing metabolic diseases such as obesity and diabetes. Evidences suggest that
      cathepsin B (CTSB), a papain-like cysteine peptidase protein, can modulate
      autophagy processes in adipocytes. This review will focus on the role of CTSB in
      autophagy under conditions of obesity.

PMID- 30107167
TI  - Pimozide suppresses colorectal cancer via inhibition of Wnt/beta-catenin
      signaling pathway.
AB  - OBJECTIVE: Wnt/beta-catenin signaling pathway plays important role in colorectal
      cancer (CRC) and acts as a potential therapeutic target. Pimozide is a FDA
      approved clinical drug used to treat psychotic diseases and it has shown
      anticancer effect in some tumors partially via inhibition of Wnt/beta-catenin
      signaling pathway. This study aimed to investigate whether pimozide exerts
      anticancer effect on CRC and explore underlying mechanism. METHODS AND RESULTS:
      Pimozide was administrated to treat HCT116 and SW480 cells. Quantitative real
      time polymerase chain reaction and western blot were used to detect the
      expression of epithelial-to-mesenchymal transition markers and Wnt/beta-catenin
      signaling pathway-related proteins. Cell proliferation and migration were
      measured by Cell Counting Kit-8 and Transwell assays respectively. HCT116 and
      SW480 cells were subcutaneously injected into nude mice and when the volume of
      tumor grown measureable (approximately 100 mm3) animals were treated with vehicle
      saline or pimozide at a dose of 25 mg/kg.d by oral gavage and then tumor size was
      measured at 7, 14, 21 and 28 days post treatment. Pimozide dose-dependently
      inhibited cell proliferation and migration in both HCT116 and SW480 cells,
      increased expression of E-cadherin and decreased expression of N-cadherin,
      vimentin and Snail. In addition, tumor growth was inhibited by pimozide in both
      HCT116 and SW480 xenografts in vivo. Expression of beta-catenin and Wnt target
      genes c-Myc, cyclin D1, Axin 2 and survivin was reduced by pimozide treatment in
      both HCT 116 and SW480 cells. CONCLUSION: Pimozide exerts anticancer effect in
      CRC via inhibition of wnt/beta-catenin signaling pathway, suggesting it as a
      potential therapeutic drug for CRC.

PMID- 30107169
TI  - Phosphorylated delta sleep inducing peptide restores spatial memory and p-CREB
      expression by improving sleep architecture at high altitude.
AB  - AIMS: Sleep loss at high altitude (HA) play major role in worsening of
      neuropsychological functions, such as attention, memory and decision making. This
      study investigates the role of phosphorylated delta sleep inducing peptide (p
      DSIP) in improving sleep architecture during chronic hypobaric hypoxia (HH)
      exposure and restoration of spatial navigational memory. METHODS: Morris water
      maze (MWM) trained rats were exposed to HH at 7620 m. p-DSIP was injected intra
      peritoneally (10 MUg/Kg bw) during HH exposure as an intervention against sleep
      alteration. Sleep architecture was recorded telemetrically before and during HH
      exposure. Monoamines were estimated by high performance liquid chromatography
      from brain stem (BS) and hypothalamus. CREB and p-CREB level in hippocampus was
      studied by western blotting and expression of different monoamine regulatory
      enzymes in BS was measured by flow cytometry. Naloxone (1 mg/kg bw), a MU opioid
      receptor antagonist of sleep inducing effect of DSIP was also studied. KEY
      FINDINGS: p-DSIP injection daily in circadian active period (18.30 h) during
      chronic HH enhanced non rapid eye movement sleep, rapid eye movement sleep as
      well as improved MWM performance of rats. p-DSIP treatment showed lower monoamine
      level and tyrosine hydroxylase (TH) expression and increased monoamine oxidase A
      (MAO A), glutamic acid decarboxylase (GAD) and Choline acetyltransferase (ChAT)
      expression. Further, naloxone altered navigational memory by decreasing the CREB
      and p-CREB level in hippocampus suggesting suppression of sleep inducing effect
      of p-DSIP. SIGNIFICANCE: Our study demonstrates that improvement of sleep quality
      by p-DSIP restores spatial memory by up regulating CREB phosphorylation during
      simulated high altitude hypoxia.

PMID- 30107171
TI  - Tandem Duplications May Supply the Missing Genetic Alterations in Many Triple
      Negative Breast and Gynecological Cancers.
AB  - In this issue of Cancer Cell, Menghi et al. show that tandem duplications (TDs)
      are a common genetic feature of gynecological and triple-negative breast cancers.
      They also provide evidence that these TDs generate genetic alterations driving
      these cancers, which, if substantiated, will fundamentally change our
      understanding of their oncogenesis.

PMID- 30107172
TI  - Cancer-Specific Splicing Changes and the Potential for Splicing-Derived
      Neoantigens.
AB  - In this issue of Cancer Cell, Kahles et al. perform a comprehensive analysis of
      RNA splicing across cancer types and identify novel correlations between genetic
      alterations and splicing in cancer. In addition, they identify that tumor
      specific splicing has the potential to generate a large new class of tumor
      specific neoantigens.

PMID- 30107170
TI  - EGFR tyrosine kinase inhibition decreases cardiac remodeling and SERCA2a/NCX1
      depletion in streptozotocin induced cardiomyopathy in C57/BL6 mice.
AB  - AIM: Epidermal growth factor receptor (EGFR) related reactive oxygen species
      (ROS) generation results in myocardial damage. We aimed to investigate the role
      of gefitinib (EGFR-tyrosine kinase inhibitor) in diabetic cardiomyopathy (DbCM).
      METHOD: DbCM was induced by injecting streptozotocin (55 mg/kg for 5 consecutive
      days) to C57/BL6 mice intraperitoneally. Diabetic C57/BL6 mice (fasting blood
      glucose level >= 250 mg/dl) were allocated into four study groups and treated
      with two doses of gefitinib (30 mg/kg and 350 mg/kg per day) as well as ramipril
      (3 mg/kg/day) for four weeks. KEY FINDINGS: We observed a significant correlation
      between persistent hyperglycaemia with cardiac remodeling and alterations in
      myocardial architecture. Gefitinib significantly prevented lipid peroxidation
      (MDA), damage of antioxidant enzymes like superoxide dismutase (SOD), Catalase,
      glutathione (GSH) and thioredoxin reductase (TrxR). Gefitinib also prevented
      hypertrophy of myocardium evidenced by reduced heart weight to body weight ratio
      and TGF-beta related collagen deposition. Gefitinib maintained cardiac biomarkers
      like lactate dehydrogenase (LDH), Creatine Kinase-MB, brain natriuretic peptide
      (BNP) and cardiac Troponin-I (cTroponinI) indicating reduced myocardial damage.
      Decreased sarcoplasmic endoplasmic reticulum Ca2 + ATPase2a (SERCA2a) and sodium
      calcium exchanger-1 (NCX1) protein depletion after gefitinib administration
      indicated improved Ca2+ homeostasis during myocardial contractility.
      Histopathology and transmission electron microscopy clearly showed almost normal
      myofibrils and mitochondrial arrangements in gefitinib treated mice.
      SIGNIFICANCE: Our findings suggest that gefitinib protects myocardial damage in
      DbCM via balancing oxidant-antioxidant system, decreased collagen deposition as
      well as improved CKMB, BNP, cTroponinI and SERCA2a/NCX-1. Thereby, it indicated
      that gefitinib may be a potential therapeutic drug for treating DbCM.

PMID- 30107173
TI  - Pulling a MAST1 on Cisplatin Resistance.
AB  - In this issue of Cancer Cell, Jin and colleagues use a kinome-wide screen to
      identify MAST1 as a cause of cisplatin resistance. They demonstrate that this
      kinase is a novel activator of MEK1 and the MAPK cascade and that it can harness
      pathway output to block cisplatin-induced cell death.

PMID- 30107174
TI  - Synthetic Lethal and Convergent Biological Effects of Cancer-Associated
      Spliceosomal Gene Mutations.
AB  - Mutations affecting RNA splicing factors are the most common genetic alterations
      in myelodysplastic syndrome (MDS) patients and occur in a mutually exclusive
      manner. The basis for the mutual exclusivity of these mutations and how they
      contribute to MDS is not well understood. Here we report that although different
      spliceosome gene mutations impart distinct effects on splicing, they are
      negatively selected for when co-expressed due to aberrant splicing and
      downregulation of regulators of hematopoietic stem cell survival and quiescence.
      In addition to this synthetic lethal interaction, mutations in the splicing
      factors SF3B1 and SRSF2 share convergent effects on aberrant splicing of mRNAs
      that promote nuclear factor kappaB signaling. These data identify shared
      consequences of splicing-factor mutations and the basis for their mutual
      exclusivity.

PMID- 30107175
TI  - Widespread Chromosomal Losses and Mitochondrial DNA Alterations as Genetic
      Drivers in Hurthle Cell Carcinoma.
AB  - Hurthle cell carcinoma of the thyroid (HCC) is a form of thyroid cancer
      recalcitrant to radioiodine therapy that exhibits an accumulation of
      mitochondria. We performed whole-exome sequencing on a cohort of primary,
      recurrent, and metastatic tumors, and identified recurrent mutations in DAXX,
      TP53, NRAS, NF1, CDKN1A, ARHGAP35, and the TERT promoter. Parallel analysis of
      mtDNA revealed recurrent homoplasmic mutations in subunits of complex I of the
      electron transport chain. Analysis of DNA copy-number alterations uncovered
      widespread loss of chromosomes culminating in near-haploid chromosomal content in
      a large fraction of HCC, which was maintained during metastatic spread. This work
      uncovers a distinct molecular origin of HCC compared with other thyroid
      malignancies.

PMID- 30107178
TI  - Therapeutic Ablation of Gain-of-Function Mutant p53 in Colorectal Cancer Inhibits
      Stat3-Mediated Tumor Growth and Invasion.
AB  - Over half of colorectal cancers (CRCs) harbor TP53 missense mutations (mutp53).
      We show that the most common mutp53 allele R248Q (p53Q) exerts gain of function
      (GOF) and creates tumor dependence in mouse CRC models. mutp53 protein binds
      Stat3 and enhances activating Stat3 phosphorylation by displacing the phosphatase
      SHP2. Ablation of the p53Q allele suppressed Jak2/Stat3 signaling, growth, and
      invasiveness of established, mutp53-driven tumors. Treating tumor-bearing mice
      with an HSP90 inhibitor suppressed mutp53 levels and tumor growth. Importantly,
      human CRCs with stabilized mutp53 exhibit enhanced Jak2/Stat3 signaling and are
      associated with poorer patient survival. Cancers with TP53R248Q/W are associated
      with a higher patient death risk than are those having nonR248 mutp53. These
      findings identify GOF mutp53 as a therapeutic target in CRC.

PMID- 30107176
TI  - Integrated Genomic Analysis of Hurthle Cell Cancer Reveals Oncogenic Drivers,
      Recurrent Mitochondrial Mutations, and Unique Chromosomal Landscapes.
AB  - The molecular foundations of Hurthle cell carcinoma (HCC) are poorly understood.
      Here we describe a comprehensive genomic characterization of 56 primary HCC
      tumors that span the spectrum of tumor behavior. We elucidate the mutational
      profile and driver mutations and show that these tumors exhibit a wide range of
      recurrent mutations. Notably, we report a high number of disruptive mutations to
      both protein-coding and tRNA-encoding regions of the mitochondrial genome. We
      reveal unique chromosomal landscapes that involve whole-chromosomal duplications
      of chromosomes 5 and 7 and widespread loss of heterozygosity arising from
      haploidization and copy-number-neutral uniparental disomy. We also identify
      fusion genes and disrupted signaling pathways that may drive disease
      pathogenesis.

PMID- 30107177
TI  - Cooperative Enhancer Activation by TLX1 and STAT5 Drives Development of NUP214
      ABL1/TLX1-Positive T Cell Acute Lymphoblastic Leukemia.
AB  - The NUP214-ABL1 fusion is a constitutively activated tyrosine kinase that is
      significantly associated with overexpression of the TLX1 and TLX3 transcription
      factors in T cell acute lymphoblastic leukemia (T-ALL). Here we show that NUP214
      ABL1 cooperates with TLX1 in driving T-ALL development using a transgenic mouse
      model and human T-ALL cells. Using integrated ChIP-sequencing, ATAC-sequencing,
      and RNA-sequencing data, we demonstrate that TLX1 and STAT5, the downstream
      effector of NUP214-ABL1, co-bind poised enhancer regions, and cooperatively
      activate the expression of key proto-oncogenes such as MYC and BCL2. Inhibition
      of STAT5, downregulation of TLX1 or MYC, or interference with enhancer function
      through BET-inhibitor treatment leads to reduction of target gene expression and
      induction of leukemia cell death.

PMID- 30107179
TI  - A Single-Agent Dual-Specificity Targeting of FOLR1 and DR5 as an Effective
      Strategy for Ovarian Cancer.
AB  - Therapeutic antibodies targeting ovarian cancer (OvCa)-enriched receptors have
      largely been disappointing due to limited tumor-specific antibody-dependent
      cellular cytotoxicity. Here we report a symbiotic approach that is highly
      selective and superior compared with investigational clinical antibodies. This
      bispecific-anchored cytotoxicity activator antibody is rationally designed to
      instigate "cis" and "trans" cytotoxicity by combining specificities against
      folate receptor alpha-1 (FOLR1) and death receptor 5 (DR5). Whereas the in vivo
      agonist DR5 signaling requires FcgammaRIIB interaction, the FOLR1 anchor
      functions as a primary clustering point to retain and maintain a high level of
      tumor-specific apoptosis. The presented proof of concept study strategically
      makes use of a tumor cell-enriched anchor receptor for agonist death receptor
      targeting to potentially generate a clinically viable strategy for OvCa.

PMID- 30107180
TI  - The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma.

PMID- 30107181
TI  - SnapShot: Bladder Cancer.
AB  - Bladder cancers, the majority of which are urothelial carcinoma, are the most
      common urinary tract cancers. There are two major disease types, muscle-invasive
      and non-muscle-invasive, with distinct pathogenesis pathways, molecular features,
      and clinical outcomes. Recent genomic and transcriptomic data have significantly
      improved tumor sub-classification and prognostication for both patient groups and
      are informing improved approaches to treatment of muscle-invasive disease. To
      view this SnapShot, open or download the PDF.

PMID- 30107182
TI  - Endoscopic sinusotomy versus redo surgery for the treatment of chronic pouch
      anastomotic sinus in ulcerative colitis patients.
AB  - BACKGROUND AND AIMS: Pouch sinus may be a serious adverse event in patients
      undergoing ileal pouch-anal anastomosis. The aim of this study was to compare
      endoscopic sinusotomy (ESi) and redo pouch surgery in the management of pouch
      sinus. METHODS: All consecutive ulcerative colitis patients with chronic pouch
      sinuses treated with ESi versus redo surgery from 2006 to 2016 were identified.
      The primary outcomes were recurrence-free and surgery-free survivals. The
      secondary outcome was postprocedural adverse events. RESULTS: This historical
      cohort study included 226 patients (ESi, n = 141; redo surgery, n = 85). Complete
      healing of the sinus was achieved in 75 patients (53.2%) and partial healing in
      23 patients (16.3%) with ESi, and an initial complete healing (ie, no anastomotic
      leak before ileostomy closure) was obtained in 80 patients (94.1%) receiving redo
      surgery. Sinus recurrence after complete healing was seen in 17 patients (22.7%)
      treated with ESi and 28 patients (32.9%) treated with surgery (P = .15).
      Subsequent surgery was needed in 34 patients (24.1%) with ESi therapy and 18
      patients (21.2%) with initial redo surgery (P = .70). Kaplan-Meier recurrence
      free and surgery-free survivals after initial procedures showed no statistical
      difference between the 2 groups (P = .42 and P = .65, respectively). The rate of
      adverse events in the ESi group was significantly lower than that in the surgery
      group (2.5% vs 43.5%, P < .0001). CONCLUSIONS: Recurrence-free and surgery-free
      survivals were comparable between patients treated with ESi and redo surgery,
      whereas pouch redo surgery was found to be associated with a higher immediate
      complete healing rate yet a higher morbidity.

PMID- 30107184
TI  - Management of Heart Failure in Adult Congenital Heart Disease.
AB  - Heart failure (HF) in the adult with congenital heart disease (ACHD) is
      associated with high morbidity and mortality and has been implicated as the
      leading cause of death in this patient population. The diagnosis of HF in ACHD
      involves a combination of clinical suspicion from subjective patient history,
      anatomic imaging, functional diagnostic studies, and rhythm evaluation. Once
      diagnosed, the approach to management of HF in this population varies widely and
      by lesion. Unfortunately, there is a paucity of literature available delineating
      the optimal management of these patients, making clinical decision-making
      extremely challenging. In this review, we aim to summarize available evidence to
      help guide the diagnosis and management of HF in ACHD.

PMID- 30107185
TI  - Cellular senescence in osteoarthritis and anti-aging strategies.
AB  - In older adults, the prevalence of osteoarthritis (OA) increases directly with
      age and is the most common cause of chronic disability. It is necessary to
      recognize that OA is a degenerative disease that strongly correlates with age,
      and often promotes elevated levels of cartilage injury. Chondrocytes undergo an
      age-dependent decline in proliferative and synthetic capacity. It is thought that
      cellular senescence may play a significant role in the pathology of OA, with
      chondrocytes exhibiting a variety of senescence-associated phenotypes. In this
      review, we discuss cellular senescence and its relationship with OA. More
      importantly, we introduce novel strategies for the modulation of cellular
      senescence, including the use of sirtuin 6, mammalian target of rapamycin, N
      acetyl-l-cysteine, proteoglycan-4 and senolytic, which may help to delay
      senescence and improve cartilage regeneration in the aging population.

PMID- 30107183
TI  - Biochemical, demographic, and self-reported tobacco-related predictors of the
      acute heart rate response to nicotine in smokers.
AB  - Understanding the stimulatory effects of nicotine on cardiovascular function in
      humans is of great interest given the wide-spread use of different forms of
      combustible and smokeless products that deliver nicotine. An intravenous nicotine
      infusion procedure was used to evaluate factors associated with the acute heart
      rate (HR) response to nicotine (0.5 mg per 70 kg bodyweight) in a sample of 213
      smokers. We tested for differential response to nicotine based on demographic
      characteristics (race [European American vs African America], sex, body mass
      index and age); a set of blood-based biomarkers (baseline nicotine, cotinine and
      cortisol levels and nicotine metabolite ratio); and a set of self-reported
      measures related to tobacco use. Nicotine infusion was first noted to increase HR
      approximately 10 beats per minute (95% CI: 7.8-12.3) one minute post-infusion,
      and 13 beats per minute (95% CI: 11.0-15.2) two minutes post-infusion. Higher
      cortisol, lower nicotine levels, higher nicotine metabolite ratio, being female
      and greater withdrawal symptoms were independently associated with a potentiated
      increase in HR 1 or 2 min after nicotine infusion. Factors associated with the
      acute HR effects of nicotine warrant further investigation given their potential
      to inform the development of nicotine delivery systems as tobacco harm reduction
      approaches for smokers.

PMID- 30107186
TI  - Comparison of RENAL, PADUA, CSA, and PAVP Nephrometry Scores in Predicting
      Functional Outcomes After Partial Nephrectomy.
AB  - OBJECTIVE: To evaluate the accuracy of radius, exophytic/endophytic, nearness to
      collecting system/sinus, anterior/posterior, and location relative to polar lines
      (RENAL), preoperative aspects and dimensions used for anatomical classification
      (PADUA), contact surface area (CSA), and preoperative assessment of volume
      preservation (PAVP) nephrometry scores in predicting postoperative renal
      functional outcomes after partial nephrectomy (PN). Few studies have compared the
      accuracy of tumor complexity systems directly in the same set of PN patients.
      MATERIALS AND METHODS: Patients treated with robotic, laparoscopic, or open PN
      having available imaging (n = 344) were examined. The ability of 4 systems to
      predict nadir estimated glomerular filtration rate (eGFR [median postoperative
      day 1]) and new baseline eGFR (median: 0.95 year) was analyzed using univariable
      and multivariable models. RESULTS: Median preoperative, nadir, and new baseline
      eGFR were 79 (interquartile range [IQR]: 63-97), 65 (IQR: 47-85), and 80 (IQR: 63
      99) mL/min/1.73 m2. Multivariable models incorporating RENAL, PADUA, CSA, or PAVP
      were similarly predictive of postoperative renal function (nadir eGFR: R2 = 0.683
      0.688, new baseline eGFR: R2 = 0.775). In univariable analysis, all 4 complexity
      systems were predictors of nadir GFR (each P < .05), with RENAL (P = .045), CSA
      (P = .027), and PAVP (P = .012) also significantly predicting nadir eGFR in
      multivariable models. No complexity system was significantly associated with new
      baseline eGFR in multivariable analysis, with only RENAL (P = .023) and PAVP (P =
      .049) having a statistically significant association in univariable analysis.
      CONCLUSION: RENAL, PADUA, CSA, and PAVP are all predictors of early postoperative
      renal function. RENAL and PAVP provided the greatest predictive ability for later
      renal functional outcomes.

PMID- 30107187
TI  - Radiation Effect on Male Spermatogenesis and Fertility-The Science and Ethical
      Consideration of the Oregon and Washington Radiation Experiments on Prison
      Inmates.

PMID- 30107188
TI  - Association Between Prostate Magnetic Resonance Imaging and Observation for Low
      risk Prostate Cancer.
AB  - OBJECTIVE: To evaluate the association between prostate magnetic resonance
      imaging (MRI) and the use of observation for men with low-risk prostate cancer
      (PCa). MATERIALS AND METHODS: We used the Surveillance, Epidemiology, and End
      Results-Medicare database to identify men diagnosed with low-risk PCa during 2010
      2013. We assessed the use of prostate MRI and management using claims in period
      surrounding PCa diagnosis. The relation of clinical and demographic factors to
      receipt of MRI was evaluated with multivariable logistic regression analysis.
      Following propensity score matching, we fit conditional logistic regression
      models to examine the association between prostate MRI and initial management,
      ie, observation or definitive treatment. RESULTS: Of 8144 patients with low-risk
      PCa, 495 (6.1%) received MRI. Use of MRI increased from 3.4% in 2010 to 10.5% in
      2013. A total of 3060 (37.6%) patients received observation. MRI was performed in
      265 (8.7%) of patients receiving observation, and 230 (4.5%) who were treated (P
      < .0001). In multivariable analysis, measures of socioeconomic status were
      significantly associated with the use of prostate MRI. Following propensity score
      matching, receipt of prostate MRI surrounding the diagnosis of PCa was associated
      with a significantly higher likelihood of observation (odds ratio = 1.90, 95%
      confidence interval: 1.56-2.32). This effect persisted in sensitivity analyses
      attempting to exclude treatment-planning MRIs. CONCLUSION: Receipt of prostate
      MRI surrounding PCa diagnosis was associated with a nearly 2-fold greater odds of
      receiving observation vs definitive treatment.

PMID- 30107189
TI  - Tumor necrosis factor alpha-induced protein 8 expression as a predictor of
      prognosis and resistance in patients with advanced ovarian cancer treated with
      neoadjuvant chemotherapy.
AB  - We explored the correlation of tumor necrosis factor alpha-induced protein 8
      (TNFAIP8) with platinum resistance in ovarian cancers (OCs) treated with
      neoadjuvant chemotherapy (NACT). We observed a significant trend of decreased
      TNFAIP8 expression after NACT (P=.042), and the extent of decreased TNFAIP8
      expression following NACT was positively associated with response to NACT
      (P=.013). Interestingly, in patients treated with NACT, the extent of decreased
      TNFAIP8 expression following NACT in tumor (change in immunohistochemistry
      [DeltaIHC] score<=-1 vs. DeltaIHC score>=0; P=.001) correlated significantly with
      overall survival (OS). Furthermore, TNFAIP8 knockout inhibited tumor
      proliferation in a time-dependent manner and arrested the cell cycle in the G0/G1
      phase in OVCAR-3 cells. In vitro, OVCAR-3 cells with downregulated TNFAIP8
      exhibited greater chemosensitivity as well as increased autophagy-related protein
      (Beclin 1 and LC II) expression. We propose that the degree of decreased TNFAIP8
      expression is a biomarker for predicting NACT resistance, and TNFAIP8 may be
      involved in cisplatin-induced chemoresistance by interacting with autophagy
      related proteins and may be a therapeutic target for OC treatment.

PMID- 30107190
TI  - Influence of citicoline on citalopram-induced antidepressant activity in
      depressive-like symptoms in male mice.
AB  - Depression is associated with significant functional disabilities. Application of
      new drugs which could enhance the effectiveness of antidepressants drug and
      reduce side effects of their long-term use seems necessary. Citicoline is used as
      an effective chemical agent for improving the symptoms of some neurodegenerative
      diseases. Therefore, in this survey, the application of citicoline as an adjuvant
      drug was evaluated in mice model of depression. A total of 180 adult NMRI male
      albino mice were used in this study. All groups were exposed to chronic
      unexpected mild stress (CUMS) followed by treatment with various doses of
      citalopram or/and citicoline or saline for 21 days. Sucrose preference (SP), open
      field (OF), and forced swimming test (FST) were applied to evaluate depression
      symptoms in the groups. The results indicated that only citicoline at the 5 mg/kg
      dose had shifted its status from being noneffective to become significantly
      effective in the co-administered group. The means of SP, OFT, and FST of the
      treatment groups were significantly different in favor of co-administered group
      compared with the other groups as well as the control group. Based on the
      results, it can be concluded that administration of citicoline, as an adjuvant
      drug, in combination with citalopram, enhanced the effectiveness of selective
      serotonin reuptake inhibitors (SSRI) drugs for depression treatment.

PMID- 30107191
TI  - Enhanced neural responses to monetary rewards in methamphetamine use disordered
      individuals compared to healthy controls.
AB  - Converging evidence supports that addiction involves the pathological usurpation
      of normal reward processes. However, the nature and direction of reward
      processing dysfunction in substance abusers remain unclear. The current study
      explored the electrophysiological responses associated with different stages of
      reward processing in methamphetamine (MA) use disordered individuals.
      Electroencephalography recording was used to compare responses of 21 MA use
      disordered individuals and 22 healthy controls (HC) while participants engaged in
      a simple gambling task. Compared to HC, MA use disordered individuals made more
      risky choices following a loss outcome on a previous trial. During the reward
      anticipatory stage, MA use disordered individuals showed an enhanced stimulus
      preceding negativity (SPN), as compared to HC. During the reward outcome stage,
      MA use disordered individuals showed an enhanced feedback-related negativity
      (FRN) for the losses versus gains as compared to HC. Furthermore, an enhanced
      P300 was observed under the gain condition, but not under the loss condition, in
      MA use disordered individuals as compared to HC. These findings provide further
      evidence that MA use disordered individuals have a sensitized neural response to
      non-drug rewards and support the impulsivity and incentive sensitization theories
      in MA use disordered individuals. The current study helps to elucidate the neural
      mechanisms of reward processing in MA use disordered individuals.

PMID- 30107192
TI  - Diagnostic neuroimaging markers of obsessive-compulsive disorder: Initial
      evidence from structural and functional MRI studies.
AB  - As of yet, no diagnostic biomarkers are available for obsessive-compulsive
      disorder (OCD), and its diagnosis relies entirely upon the recognition of
      behavioural features assessed through clinical interview. Neuroimaging studies
      have shown that various brain structures are abnormal in OCD patients compared to
      healthy controls. However, the majority of these results are based on average
      differences between groups, which limits diagnostic usage in clinical practice.
      In recent years, a growing number of studies have applied multivariate pattern
      analysis (MVPA) techniques on neuroimaging data to extract patterns of altered
      brain structure, function and connectivity typical for OCD. MVPA techniques can
      be used to develop predictive models that extract regularities in data to
      classify individual subjects based on their diagnosis. In the present paper, we
      reviewed the literature of MVPA studies using data from different imaging
      modalities to distinguish OCD patients from controls. A systematic search
      retrieved twelve articles that fulfilled the inclusion and exclusion criteria.
      Reviewed studies have been able to classify OCD diagnosis with accuracies ranging
      from 66% up to 100%. Features important for classification were different across
      imaging modalities and widespread throughout the brain. Although studies have
      shown promising results, sample sizes used are typically small which can lead to
      high variance of the estimated model accuracy, cohort-specific solutions and lack
      of generalizability of findings. Some of the challenges are discussed that need
      to be overcome in order to move forward toward clinical applications.

PMID- 30107193
TI  - Comparative transcriptomics of two Valsa pyri isolates uncover different
      strategies for virulence and growth.
AB  - Valsa pyri, an ascomycete pathogen that is a member of the Valsaceae family
      (Sordariomycetes, Diaporthales), which causes pear or apple canker and leads to
      tree death and massive yield losses. Here, we selected two V. pyri isolates (Vp14
      and Vp297) that exhibited different invasion abilities for transcriptomics
      analyses. Compared toVp297, Vp14 had stronger virulence and spread faster on host
      like nutrients. Four samples, including mycelium or infectious mycelium, of the
      two isolates were sequenced. Clean reads were mapped to the V. pyri genome, and
      12490 transcripts and 178 new genes were identified. There were dramatically
      fewer differentially expressed genes (DEGs) in Vp14 than in Vp297. According to
      GO and COG annotations, there were both more up- and down-regulated genes in
      Vp297 than in Vp14 except for genes involved in amino acid transport and
      metabolism, carbohydrate transport and metabolism, peroxidases and so on.
      Specific up-regulated DEGs, including genes encoding cell wall degrading enzymes
      and genes involved in nitrogen metabolism and peroxidases which play crucial
      roles in virulence and infectious growth, were especially enriched inVp14. These
      results indicate that the Vp14 isolate may infect its host and take up nutrition
      more efficiently, reflecting a stronger ability for invasion or infectious
      growth. Our analysesindicate that a successful V. pyri infection involves
      multiple instances of transcriptome remodeling to regulate gene functions.
      Comparative transcriptomics between isolates of V. pyri may aid in our
      understanding of the virulence mechanism of this pathogen.

PMID- 30107194
TI  - Simultaneous identification and characterization of amanita toxins using liquid
      chromatography-photodiode array detection-ion trap and time-of-flight mass
      spectrometry and its applications.
AB  - Rapid and accurate identification of multiple toxins for clinical diagnosis and
      treatment of mushroom poisoning cases is still a challenge, especially with the
      lack of authentic references. In this study, we developed an effective method for
      simultaneous identification of amanita peptide toxins by liquid chromatography
      coupled with photodiode array detection and ion trap time-of-flight mass
      spectrometry. The accuracy and selectivity of the methodology were validated
      through similar multiple fragmentation patterns and characteristic ions of
      standard alpha- and beta-amanitin. The developed method could successfully
      separate and identify major toxic constituents in Amanita mushrooms. Two
      amatoxins and three phallotoxins were confirmed in a single run through their
      fragmentation patterns and characteristic ions, which can be used as diagnostic
      fragment ions to identify mushroom toxins in complex samples. Furthermore, the
      performance of the developed method was verified by using real biological
      samples, including plasma and urine samples collected from rats after
      intraperitoneal administration of toxins. Thus, the development methodology could
      be crucial for the accurate detection of mushroom toxins without standard
      references.

PMID- 30107195
TI  - Poincare plot indices as measures of sympathetic cardiac regulation: Responses to
      psychological stress and associations with pre-ejection period.
AB  - The Poincare plot is a visual representation of the R-R time series within a
      Cartesian plane constructed by plotting each R-R interval as a function of the
      previous one. The plot can be characterized by parameters that quantify the
      standard deviation (SD) of short- and long-term R-R interval variability (SD1 and
      SD2, respectively). Claims regarding the use of Poincare plot analysis as an
      alternative to conventional time-domain and spectral analytic measures of
      parasympathetic contributions to heart rate variability (HRV) have been evaluated
      somewhat extensively. However, its proposed utility for characterizing
      sympathetic influences on HRV during periods of acute mental stress, using SD2
      and the SD1/SD2 ratio, has received minimal attention. In the present study, the
      electrocardiogram was used to record R-R interval variability in healthy
      participants during a resting baseline period, while they performed a challenging
      reaction time task, and then during a recovery period. Simultaneously, the
      thoracic impedance cardiogram was used to derive the pre-ejection period (PEP),
      which reflects sympathetic cardiac control. HRV was quantified using time-domain,
      spectral analytic, and Poincare plot indices. Task performance elicited
      significant reductions in HRV and PEP parameters, indicating withdrawal of
      parasympathetic tone with concomitant sympathetic activation. Following cessation
      of task performance, all HRV and impedance measures returned to baseline levels,
      signaling resumption of parasympathetic dominance. Bivariate associations linking
      SD2 and the SD1/SD2 ratio to PEP were observed; however, these were not large in
      magnitude, were exceeded in size by associations between the Poincare metrics and
      conventional HRV markers of parasympathetic cardiac influences, and were
      eliminated when the latter were controlled statistically. These observations
      challenge the proposal that the Poincare SD2 and SD1/SD2 metrics are suitable
      markers of sympathetic cardiac regulation in research concerned with mental and
      physical health.

PMID- 30107197
TI  - Inflamed 'meat that thinks': A depressed person's perspective on inflammation and
      depression.

PMID- 30107196
TI  - Gut microbiota associated with pulmonary tuberculosis and dysbiosis caused by
      anti-tuberculosis drugs.
AB  - BACKGROUND: An improved understanding of the gut microbiota could lead to better
      strategies for the diagnosis, therapy and prophylaxis of tuberculosis (TB). The
      impact of both Mycobacterium tuberculosis (Mtb) infection and anti-TB treatment
      on the gut microbiota has rarely been studied. METHODS: We characterized the
      diversity and composition of the gut microbiota in pulmonary TB patients as well
      as the effects of anti-TB drugs on the gut microbiota. RESULTS: Pulmonary Mtb
      infection led to a minor decrease in the alpha diversity of the gut microbiota
      when compared to healthy controls, which mainly resulted from changes in the
      relative abundance of the members of genus Bacteroides. Anti-TB therapy caused a
      rapid, significant alteration in the community structure. The relative abundance
      of members of genus Clostridiales of the phylum Firmicutes significantly
      decreased during anti-TB treatment, while many members of genus Bacteroides,
      including Bacteroides OTU230 and Bacteroides fragilis, were among the taxa that
      increased. OTU8 and OTU2972 assigned to family Erysipelotrichaceae of the phylum
      Firmicutes showed a dramatic increase 1 week after the start of therapy, while
      the other members of this family decreased. CONCLUSIONS: Pulmonary TB and anti-TB
      treatment caused a distinct dysbiosis of the gut microbiota. Our study
      contributes valuable information implying potential links between the gut
      microbiota and TB.

PMID- 30107198
TI  - Female mice are protected from space radiation-induced maladaptive responses.
AB  - Interplanetary exploration will be humankind's most ambitious expedition and the
      journey required to do so, is as intimidating as it is intrepid. One major
      obstacle for successful deep space travel is the possible negative effects of
      galactic cosmic radiation (GCR) exposure. Here, we investigate for the first time
      how combined GCR impacts long-term behavioral and cellular responses in male and
      female mice. We find that a single exposure to simulated GCR induces long-term
      cognitive and behavioral deficits only in the male cohorts. GCR exposed male
      animals have diminished social interaction, increased anxiety-like phenotype and
      impaired recognition memory. Remarkably, we find that the female cohorts did not
      display any cognitive or behavioral deficits after GCR exposure. Mechanistically,
      the maladaptive behavioral responses observed only in the male cohorts correspond
      with microglia activation and synaptic loss in the hippocampus, a brain region
      involved in the cognitive domains reported here. Furthermore, we measured
      reductions in AMPA expressing synaptic terminals in the hippocampus. No changes
      in any of the molecular markers measured here are observed in the females. Taken
      together these findings suggest that GCR exposure can regulate microglia activity
      and alter synaptic architecture, which in turn leads to a range of cognitive
      alterations in a sex dependent manner. These results identify sex-dependent
      differences in behavioral and cognitive domains revealing promising cellular and
      molecular intervention targets to reduce GCR-induced chronic cognitive deficits
      thereby boosting chances of success for humans in deep space missions such as the
      upcoming Mars voyage.

PMID- 30107199
TI  - Extracellular biosynthesis of biocompatible cadmium sulfide quantum dots using
      Trametes versicolor.
AB  - Quantum dots are important fluorescent semiconductor nano-crystals with
      distinguished electrical and optical properties and have gained great interest in
      many fields. The chemical and physical synthetic methods are usually not
      favorable for biological application due to high energy-consumption procedure and
      residual toxic chemicals. The development of novel "green" routes to prepare bio
      compatible cadmium sulfide quantum dots constitutes a promising substituted
      approach. We used the white rot fungus Trametes versicolor for the biosynthesis
      of cadmium sulfide quantum dots taking account of the adsorption property of this
      fungus. Multiple physical characterizations involving scanning electron
      microscope (SEM), ultraviolet-visible (UV-vis) and photoluminescence (PL)
      spectroscopy, fourier transform infrared spectroscopy (FTIR), thermo-gravimetric
      (TG), transmission electron microscopy (TEM) and X-ray diffraction (XRD)
      confirmed surface, optical and thermal characteristics, crystalline nature, size
      and shape distributions of the nanoparticles. This study provided a suitable and
      efficient approach to synthesize stable biocompatible cadmium sulfide quantum
      dots using the fungus Trametes versicolor with great potentials in the biological
      and biomedical researches.

PMID- 30107200
TI  - Protective effects of dopamine D2/D3 receptor agonist piribedil on learning and
      memory of rats exposed to global cerebral ischemia-reperfusion.
AB  - Global cerebral ischemia-reperfusion (GCI/R) may occur after any of several
      clinical conditions such as cardiac arrest and anesthetic accident. Some dopamine
      receptor agonists possess neuroprotective effects. However, some of them may
      produce side effects during treatment. Piribedil, which is a dopamine D2/D3
      receptor agonist, has fewer side effects and is well tolerated. This study
      investigated the effects of piribedil on learning and memory of rats with GCI/R
      according to modified neurological severity score (mNSS) scoring and Morris water
      maze test (MWM). Rats with GCI/R were treated with piribedil 25 or 50 mg/kg/d,
      and mNSS was performed at 6 h, 1 day, 3 days, and 1 and 2 weeks after injury. The
      MWM test was employed to evaluate learning and memory of rats at 1 and 2 weeks
      after injury. The results showed treatment with piribedil reduced the mNSS score
      and prolonged the time in the target quadrant compared with untreated rats
      although no obvious differences of the 25 and 50 mg/kg/d piribedil intervention
      groups were observed statistically. Piribedil is effective in improving the
      neurological function and learning and memory of rats after GCI/R.

PMID- 30107201
TI  - Methoxychlor and its metabolite HPTE inhibit rat neurosteroidogenic 3alpha
      hydroxysteroid dehydrogenase and retinol dehydrogenase 2.
AB  - Methoxychlor is primarily used as an insecticide and it is widely present in the
      environment. The objective of the present study was to investigate the direct
      effects of methoxychlor and its metabolite hydroxychlor (HPTE) on rat
      neurosteroidogenic 3alpha-hydroxysteroid dehydrogenase (AKR1C14) and retinol
      dehydrogenase 2 (RDH2) activities. Rat AKR1C14 and RDH2 were cloned and expressed
      in COS-1 cells, and the effects of methoxychlor and HPTE on these enzymes were
      measured. HPTE was more potent to inhibit AKR1C14 and RDH2 activities than
      methoxychlor, with IC50 values of 2.602 +/- 0.057 MUM and 20.473 +/- 0.049 MUM,
      respectively, while those of methoxychlor were over 100 MUM. HPTE competitively
      inhibited AKR1C14 and RDH2 when steroid substrates were used, while it showed a
      mode of mixed inhibition on these enzymes when NADPH/NAD+ were used. We
      elucidated the binding mode of methoxychlor and HPTE to the crystal structure of
      AKR1C14 by molecular docking and found that HPTE had higher affinity with the
      enzyme than methoxychlor. In conclusion, HPTE is more potent than methoxychlor to
      inhibit both AKR1C14 and RDH2.

PMID- 30107202
TI  - Serotonin, hematopoiesis and stem cells.
AB  - A large number of studies have focused on the role of serotonin as a
      neurotransmitter in the central nervous system, although only a small percentage
      of the body's serotonin (~5%) can be found in the mature brain of mammals. In the
      gut, the enterochromaffin cells are scattered in the enteric epithelium from the
      stomach through the colon and produce over 95% of the body's serotonin. Since the
      generation of tryptophan hydroxylase (Tph1 and Tph2) knockout mice, unsuspected
      roles have been identified for serotonin synthesized outside the brain. Moreover,
      the murine model deficient in peripheral serotonin (Tph1-/-) is a unique
      experimental tool for exploring the molecular and cellular mechanisms involving
      serotonin's local effects through microserotonergic systems. In this review, we
      focus on peripheral serotonin and its role on progenitor or stem cells as well as
      on hematopoietic progenitors. We discuss the possible role of serotonin in
      hematopoietic diseases, and whether targeting the serotonergic system could be of
      therapeutic value for the regulation of normal and pathological hematopoiesis.

PMID- 30107203
TI  - Atheroprotective effects and molecular targets of bioactive compounds from
      traditional Chinese medicine.
AB  - Traditional Chinese medicine (TCM) has served the Chinese people since antiquity,
      and is playing an important role in today's healthcare. However, there has been
      controversy in the use of these traditional herbs due to unclear components and
      absence of scientific proof. As China plans to modernize traditional medicine,
      successful attempts to better understand the molecular mechanisms of TCM have
      been made by focusing on isolating active ingredients from these remedies. In
      this review, we critically examined the current evidence on atheroprotective
      effects of bioactive compounds from TCM using in vitro or in vivo models in the
      past two decades. A total of 47 active compounds were included in our review,
      which were introduced in the order of chemical structures, source, model,
      efficacy and mechanism. Notablely, this review highlighted the cellular and
      molecular mechanisms of these active compounds in prevention and treatment of
      atherosclerosis. Two compounds were also involved in double-blind, randomized,
      placebo-controlled clinical trials (RCTs). Besides, we introduced the
      legislations of the People's Republic of China ensuring quality and safety of
      products used in TCM. In summary, studies on bioactive compounds from TCM will
      provide a new approach for better management of atherosclerosis.

PMID- 30107204
TI  - Inter-subject correlation of temporoparietal junction activity is associated with
      conflict patterns during flexible decision-making.
AB  - Although behavioral flexibility and conflict regulation may rely on executive
      function, the mechanism underlying these relationships remains obscure. We
      studied whether subjects' conflict ratings were associated with right
      dorsolateral prefrontal cortex (rDLPFC) and temporoparietal junction (rTPJ)
      activity during flexible decision-making in a moral dilemma task using inter
      subject correlation (ISC)-based approach (i.e., brain-behavior correlation
      matrices analysis). We observed a statistically significant positive correlation
      between the ISC matrix of rTPJ and conflict-scores. This implies that similar
      rTPJ activity patterns across subjects were associated with similar conflict
      rating patterns across subjects. Our findings suggest that rTPJ activity may be
      also related to conflicting experience.

PMID- 30107205
TI  - Potential biomarkers for distinguishing people with Alzheimer's disease from
      cognitively intact elderly based on the rich-club hierarchical structure of white
      matter networks.
AB  - The aim of this study is to identify potential biomarkers that may distinguish
      people with Alzheimer's disease (AD) from cognitively intact elderly. We analyzed
      the features of rich-club hierarchical network between the AD and a control group
      by diffusion tensor imaging. We detected that the changes between the two groups
      were located mainly in the feeder and local connections. Then, we calculated the
      betweenness centrality of the rich nodes and the strength values of all feeder
      connections, and we chose the nodes and connections that showed the most
      significant differences as features. We found that 1) Feeder and local
      connections were changed in the AD group; 2) Rich nodes of the left putamen and
      precuneus had significant differences in betweenness centrality between the AD
      and control groups; 3) Three connections showed significant differences. The
      obtained features were fed into a linear discriminant analysis for classifying AD
      from cognitively intact elderly. The classification accuracy is superior to that
      of traditional biomarkers (hippocampal volume and clinical scores). Our results
      suggested that rich-club hierarchical network analysis is a viable tool for
      finding potential biomarkers. The obtained features can be applied as potential
      biomarkers for distinguishing AD patients from cognitively intact elderly.

PMID- 30107206
TI  - Long-lasting, reversible and non-neurotoxic inactivation of hippocampus activity
      induced by neosaxitoxin.
AB  - BACKGROUND: Neosaxitoxin (NeoSTX) and related paralytics shellfish toxins has
      been successfully used as local anesthetic and muscle relaxants to treat a
      variety of ailments. The primary mechanism of action of these toxins occurs by
      blocking voltage-gated sodium channels with compounds such as TTX, lidocaine, or
      derivatives. However, most of these non-classical sodium channel blockers act
      with a reduced time effect as well as ensuing neurotoxicity. NEW METHOD: In this
      report, we show that the use of local NeoSTX injections inactivates the
      hippocampal neuronal activity reversibly with a by long-term dynamics, without
      neuronal damage. RESULTS: A single 10 ng/MUl injection of NeoSTX in the dorsal
      CA1 region abolished for up to 48 h memory capacities and neuronal activity
      measured by the neuronal marker c-fos. After 72 h of toxin injection, the animals
      fully recover their memory capacities and hippocampal neuronal activity. The
      histological inspection of NeoSTX injected brain regions revealed no damage to
      the tissue or reactive gliosis, similar to vehicle injection. Acute
      electrophysiological recording in vivo shows, also, minimal spreading of the
      NeoSTX in the cerebral tissue. COMPARISON WITH EXISTING METHODS: Intracerebral
      NeoSTX injection showed longer effects than other voltage sodium channel blocker,
      with minimal spreading and no neuronal damage. CONCLUSION: NeoSTX is a new useful
      tool that reversibly inactivates different brains region for a long time, with
      minimal diffusion and without neuronal damage. Moreover, NeoSTX can be used as a
      valuable sodium channel blocker for many studies in vivo and with potential
      therapeutic uses.

PMID- 30107207
TI  - Animal models of early-stage Parkinson's disease and acute dopamine deficiency to
      study compensatory neurodegenerative mechanisms.
AB  - Parkinson's disease is a common neurodegenerative disease characterized by a
      widely variety of motor and non-motor symptoms. While the motor deficits are only
      visible following a severe dopamine depletion, neurodegenerative process and some
      non-motor symptoms are manifested years before the motor deficits. Importantly,
      chronic degeneration of dopaminergic neurons leads to the development of
      compensatory mechanisms that play roles in the progression of the disease and the
      response to anti-parkinsonian therapies. The identification of these mechanisms
      will be of great importance for improving our understanding of factors with
      important contributions to the disease course and the underlying adaptive
      process. To date, most of the data obtained from animal models reflect the late,
      chronic, dopamine-depleted states, when compensatory mechanisms have already been
      established. Thus, adequate animal models with which researchers are able to
      dissect early- and late-phase mechanisms are necessary. Here, we reviewed the
      literature related to animal models of early-stage PD and pharmacological
      treatments capable of inducing acute dopamine impairments and/or depletion, such
      as reserpine, haloperidol and tetrodotoxin. We highlighted the advantages,
      limitations and the future prospective uses of these models, as well as their
      applications in the identification of novel agents for treating this neurological
      disorder.

PMID- 30107208
TI  - A sleep spindle detection algorithm that emulates human expert spindle scoring.
AB  - BACKGROUND: Sleep spindles are a marker of stage 2 NREM sleep that are linked to
      learning & memory and are altered by many neurological diseases. Although visual
      inspection of the EEG is considered the gold standard for spindle detection, it
      is time-consuming, costly and can introduce inter/ra-scorer bias. NEW METHOD: Our
      goal was to develop a simple and efficient sleep-spindle detector (algorithm #7,
      or 'A7') that emulates human scoring. 'A7' runs on a single EEG channel and
      relies on four parameters: the absolute sigma power, relative sigma power, and
      correlation/covariance of the sigma band-passed signal to the original EEG
      signal. To test the performance of the detector, we compared it against a gold
      standard spindle dataset derived from the consensus of a group of human experts.
      RESULTS: The by-event performance of the 'A7' spindle detector was 74% precision,
      68% recall (sensitivity), and an F1-score of 0.70. This performance was
      equivalent to an individual human expert (average F1-score = 0.67). COMPARISON
      WITH EXISTING METHOD(S): The F1-score of 'A7' was 0.17 points higher than other
      spindle detectors tested. Existing detectors have a tendency to find large
      numbers of false positives compared to human scorers. On a by-subject basis, the
      spindle density estimates produced by A7 were well correlated with human experts
      (r2 = 0.82) compared to the existing detectors (average r2 = 0.27). CONCLUSIONS:
      The 'A7' detector is a sensitive and precise tool designed to emulate human
      spindle scoring by minimizing the number of 'hidden spindles' detected. We
      provide an open-source implementation of this detector for further use and
      testing.

PMID- 30107209
TI  - Strain partitioning between nerves and axons: Estimating axonal strain using
      sodium channel staining in intact peripheral nerves.
AB  - BACKGROUND: Peripheral nerves carry afferent and efferent signals between the
      central nervous system and the periphery of the body. When nerves are strained
      above physiological levels, conduction blocks occur, resulting in debilitating
      loss of motor and sensory function. Understanding the effects of strain on nerve
      function requires knowledge of the multi-scale mechanical behaviour of the
      tissue, and how this is transferred to the cellular environment. NEW METHOD: The
      aim of this work was to establish a technique to measure the partitioning of
      strain between tissue and axons in axially loaded peripheral nerves. This was
      achieved by staining extracellular domains of sodium channels clustered at nodes
      of Ranvier, without altering tissue mechanical properties by fixation or
      permeabilisation. RESULTS: Stained nerves were imaged by multi-photon microscopy
      during in situ tensile straining, and digital image correlation was used to
      measure axonal strain with increasing tissue strain. Strain was partitioned
      between tissue and axon scales by an average factor of 0.55. COMPARISONS WITH
      EXISTING METHODS: This technique allows non-invasive probing of cell-level strain
      within the physiological tissue environment. CONCLUSIONS: This technique can help
      understand the mechanisms behind the onset of conduction blocks in injured
      peripheral nerves, as well as to evaluate changes in multi-scale mechanical
      properties in diseased nerves.

PMID- 30107211
TI  - Muscle fibrosis in the soft palate: Delivery of cells, growth factors and anti
      fibrotics.
AB  - The healing of skeletal muscle injuries after major trauma or surgical
      reconstruction is often complicated by the development of fibrosis leading to
      impaired function. Research in the field of muscle regeneration is mainly focused
      on the restoration of muscle mass while far less attention is paid to the
      prevention of fibrosis. In this review, we take as an example the reconstruction
      of the muscles in the soft palate of cleft palate patients. After surgical
      closure of the soft palate, muscle function during speech is often impaired by a
      shortage of muscle tissue as well as the development of fibrosis. We will give a
      short overview of the most common approaches to generate muscle mass and then
      focus on strategies to prevent fibrosis. These include anti-fibrotic strategies
      that have been developed for muscle and other organs by the delivery of small
      molecules, decorin and miRNAs. Anti-fibrotic compounds should be delivered in
      aligned constructs in order to obtain the organized architecture of muscle
      tissue. The available techniques for the preparation of aligned muscle constructs
      will be discussed. The combination of approaches to generate muscle mass with
      anti-fibrotic components in an aligned muscle construct may greatly improve the
      functional outcome of regenerative therapies for muscle injuries.

PMID- 30107210
TI  - Optimal positioning of optodes on the scalp for personalized functional near
      infrared spectroscopy investigations.
AB  - BACKGROUND: Application of functional Near InfraRed Spectroscopy (fNIRS) in
      neurology is still limited as a good optical coupling and optimized optode
      coverage of specific brain regions remains challenging, notably for prolonged
      monitoring. METHODS: We propose to evaluate a new procedure allowing accurate
      investigation of specific brain regions. The procedure consists in: (i) A priori
      maximization of spatial sensitivity of fNIRS measurements targeting specific
      brain regions, while reducing the number of applied optodes in order to decrease
      installation time and improve subject comfort. (ii) Utilization of a 3D
      neuronavigation device and usage of collodion to glue optodes on the scalp,
      ensuring good optical contact for prolonged investigations. (iii) Local
      reconstruction of the hemodynamic activity along the cortical surface using
      inverse modelling. RESULTS: Using realistic simulations, we demonstrated that
      maps derived from optimal montage acquisitions showed, after reconstruction,
      spatial resolution only slightly lower to that of ultra high density montages
      while significantly reducing the number of optodes. The optimal montages provided
      overall good quantitative accuracy especially at the peak of the spatially
      reconstructed map. We also evaluated real motor responses in two healthy subjects
      and obtained reproducible motor responses over different sessions. COMPARISON
      WITH EXISTING METHODS: We are among the first to propose a mathematical
      optimization strategy, allowing high sensitivity measurements. CONCLUSIONS: Our
      results support that using personalized optimal montages should allow to conduct
      accurate fNIRS studies in clinical settings and realistic lifestyle conditions.

PMID- 30107212
TI  - Extended HLA-G genetic diversity and ancestry composition in a Brazilian admixed
      population sample: Implications for HLA-G transcriptional control and for case
      control association studies.
AB  - Human leukocyte antigen-G (HLA-G) is a nonclassical Major Histocompatibility
      Complex (MHC) molecule with immunomodulatory function and restricted tissue
      expression. The genetic diversity of HLA-G has been extensively studied in
      several populations, however, the segment located upstream -1406 has not yet been
      evaluated. We characterized the nucleotide variation and haplotype structure of
      an extended distal region (-2635), all exons and the 3'UTR segment of HLA-G by
      next-generation sequencing (NGS) in a sample of 335 Brazilian individuals. We
      detected 29 variants at the HLA-G distal promoter region, arranged into 19
      haplotypes, among which we identified sites that may influence transcription
      factor targeting. Although the variation pattern in the distal region resembled
      the one observed in the conventional promoter segment, molecular signature for
      balancing selection was observed in the promoter segment from -1406 to -1
      (Tajima's D = 2.315, P = 0.017), but not in this distal segment (D = 1.049, P =
      0.118). Furthermore, the ancestry composition of this Brazilian population sample
      was determined by the analysis of SNPforID 34-plex ancestry informative marker
      (AIM) SNP panel. The distribution of HLA-G haplotypes was ancestry-dependent,
      corroborating previous findings and emphasizing the importance of considering the
      ancestry information in association studies.

PMID- 30107213
TI  - Full-length extension of HLA allele sequences by HLA allele-specific hemizygous
      Sanger sequencing (SSBT).
AB  - The gold standard for typing at the allele level of the highly polymorphic Human
      Leucocyte Antigen (HLA) gene system is sequence based typing. Since sequencing
      strategies have mainly focused on identification of the peptide binding groove,
      full-length sequence information is lacking for >90% of the HLA alleles. One of
      the goals of the 17th IHIWS workshop is to establish full-length sequences for as
      many HLA alleles as possible. In our component "Extension of HLA sequences by
      full-length HLA allele-specific hemizygous Sanger sequencing" we have used full
      length hemizygous Sanger Sequence Based Typing to achieve this goal. We selected
      samples of which full length sequences were not available in the IPD-IMGT/HLA
      database. In total we have generated the full-length sequences of 48 HLA-A, 45 -B
      and 31 -C alleles. For HLA-A extended alleles, 39/48 showed no intron differences
      compared to the first allele of the corresponding allele group, for HLA-B this
      was 26/45 and for HLA-C 20/31. Comparing the intron sequences to other alleles of
      the same allele group revealed that in 5/48 HLA-A, 16/45 HLA-B and 8/31 HLA-C
      alleles the intron sequence was identical to another allele of the same allele
      group. In the remaining 10 cases, the sequence either showed polymorphism at a
      conserved nucleotide or was the result of a gene conversion event. Elucidation of
      the full-length sequence gives insight in the polymorphic content of the alleles
      and facilitates the identification of its evolutionary origin.

PMID- 30107214
TI  - TNFalpha gene silencing mediated by orally targeted nanoparticles combined with
      interleukin-22 for synergistic combination therapy of ulcerative colitis.
AB  - Pro-resolving factors that are critical for colonic epithelial restitution were
      down-regulated during the treatment with inhibitor of pro-inflammatory cytokines
      (e.g., anti-TNFalpha antibody) in ulcerative colitis (UC) therapy. We
      hypothesized that increased amounts of factors such as interleukin-22 (IL-22)
      during the therapeutic inhibition of TNFalpha could facilitate the resolution of
      intestinal inflammation. As combination therapy is an emerging strategy for UC
      treatment, we attempt to treat established UC based on the combination of
      TNFalpha siRNA (siTNF) and IL-22. Initially, we loaded siTNF into galactosylated
      polymeric nanoparticles (NPs). The resultant Gal-siTNF-NPs had a desirable
      average diameter (~261 nm), a narrow size distribution and a slightly negative
      surface charge (~-6 mV). These NPs successfully mediated the targeted delivery of
      siTNF to macrophages and efficiently inhibited the expression of TNFalpha.
      Meanwhile, IL-22 could obviously accelerate mucosal healing. More importantly,
      oral administration of Gal-siTNF-NPs plus IL-22 embedded in a hydrogel
      (chitosan/alginate) showed much stronger capacities to down-regulate the
      expression of pro-inflammatory factors and promote mucosal healing. This
      formulation also yielded a much better therapeutic efficacy against UC in a mouse
      model compared to hydrogel loaded with Gal-siTNF-NPs or IL-22 alone. Our results
      strongly demonstrate that Gal-siTNF-NP/IL-22-embedded hydrogel can target to
      inflamed colon, and co-deliver siTNF and IL-22 to boost the effects of either
      monotherapy, which may become a promising oral drug formulation and enable
      targeted combination therapy of UC.

PMID- 30107215
TI  - Cryoprecipitate augments the global transduction of the adeno-associated virus
      serotype 9 after a systemic administration.
AB  - Adeno-associated virus (AAV) vectors have been successfully used for transgene
      delivery in clinical trials. A systemic administration of AAV vectors has been
      proposed in order to achieve global transduction, which requires that the AAV
      vector is capable of crossing the blood vessels. It has been demonstrated that
      serum proteins are able to directly interact with AAV virions to enhance liver
      transduction. In this study, we investigate whether the serum proteins have the
      potential to increase the capacity of AAV to diffuse through the endothelial
      cells and deliver the transgene into the whole body. First, we found that the
      direct interaction of serum with AAV9 virions increased the epithelial cell
      permeability of AAV9 in vitro. Several serum proteins with a potential effect on
      AAV vascular permeability have been identified from mass spectrometry analysis,
      including fibrinogen, fibronectin, von Willebrand factor (vWF), platelet factor
      4, alpha-1-acid glycoprotein, and plasminogen. The incubation of these serum
      proteins with AAV9 enhanced the global transduction in mice after a systemic
      administration. To apply these findings in clinical practice, we demonstrated
      that the clinical product cryoprecipitate (mainly containing fibrinogen and vWF)
      augmented AAV9 global transduction. The mechanism study revealed that
      cryoprecipitate slowed down the clearance of AAV9 vectors in the blood so that
      the AAV9 vectors had sufficient time to travel to the peripheral organs. In
      summary, the results from this study suggests that serum proteins interact with
      AAV virions and enhance the AAV9 vascular permeability for global transduction,
      and, more importantly, cryoprecipitate can be immediately applied for clinical
      patients who need the systemic administration of AAV vectors for global
      transduction.

PMID- 30107216
TI  - CYP46A1 protects against NMDA-mediated excitotoxicity in Huntington's disease:
      Analysis of lipid raft content.
AB  - Huntington's Disease (HD) is an autosomal dominant neurodegenerative disease
      caused by abnormal polyglutamine expansion in huntingtin (mHtt) protein leading
      to degeneration of striatal neurons. Excitotoxicity, consecutive to
      overstimulation of N-methyl d-aspartate receptors (NMDARs) has a pivotal role in
      many neurological disorders including HD. Mutant Htt causes enhanced NMDA
      sensitivity, alteration of NMDAR expression and localization in neurons.
      Excitotoxic events initiate neuronal death in numerous ways, including activation
      of apoptotic cascades. Among the NMDAR subunits involved in glutamatergic
      mediated excitotoxicity, GluN2B has been extensively reported. In addition to
      excitotoxicity, alteration of cholesterol metabolism has been observed in HD,
      with a decrease of cholesterol precursor synthesis along with an increase of
      cholesterol accumulation, which is deleterious for neurons. Expression of
      Cholesterol Hydroxylase enzyme, CYP46A1, which converts cholesterol into 24 S
      hydroxycholesterol is down-regulated in HD. We found that CYP46A1 overexpression
      is beneficial in HD neurons and mouse model, but the mechanisms involved still
      remain unclear. In this study we addressed the effect of CYP46A1 on NMDAR
      mediated excitotoxicity in HD primary neurons and its role in modulating
      cholesterol and localization of GLUN2B in lipid rafts. We showed that CYP46A1 is
      protective against NMDAR-mediated excitotoxicity in two different HD neuronal
      cell models. Cholesterol as well as GluN2B level in lipid raft, are significantly
      increased by mHtt. Despite a clear effect of CYP46A1 in reducing cholesterol
      content in lipid raft extracts from wild type neurons, CYP46A1 overexpression in
      HD neurons could not normalize the increased cholesterol levels in lipid rafts.
      This study highlights the beneficial role of CYP46A1 against NMDAR-mediated
      excitotoxicity and gives further insights into the cellular mechanisms underlying
      CYP46A1-mediated neuroprotection.

PMID- 30107217
TI  - Mechanisms of cardiac iron homeostasis and their importance to heart function.
AB  - Heart disease is a common manifestation in conditions of iron imbalance. Normal
      heart function requires coupling of iron supply for oxidative phosphorylation and
      redox signalling with tight control of intracellular iron to below levels at
      which excessive ROS are generated. Iron supply to the heart is dependent on
      systemic iron availability which is controlled by the systemic
      hepcidin/ferroportin axis. Intracellular iron in cardiomyocytes is controlled in
      part by the iron regulatory proteins IRP1/2. This mini-review summarises current
      understanding of how cardiac cells regulate intracellular iron levels, and of the
      mechanisms linking cardiac dysfunction with iron imbalance. It also highlights a
      newly-recognised mechanism of intracellular iron homeostasis in cardiomyocytes,
      based on a cell-autonomous cardiac hepcidin/ferroportin axis. This new
      understanding raises pertinent questions on the interplay between systemic and
      local iron control in the context of heart disease, and the effects on heart
      function of therapies targeting the systemic hepcidin/ferroportin axis.

PMID- 30107218
TI  - Combination of 3D printing technologies and compressed tablets for preparation of
      riboflavin floating tablet-in-device (TiD) systems.
AB  - Gastric floating tablets are a multifunctional dosage form with the merits of
      long-term gastric retention, sustained release and improved bioavailability
      though floating time and sustained release are usually not satisfied. Here we
      designed a novel gastric floating system by combining compressed tablets with 3D
      printed devices, wherein a riboflavin tablet was filled into a device. The table
      filled device can be called a tablet-in-device (TiD) system. Commercial
      poly(lactic acid) filaments were used for fused deposition modeling (FDM) 3D
      printing of the body and cap of the device. Four types of TiD systems were
      prepared. The basic structures of them involved non-net, centrally symmetric
      double-net (including a peripheral sealed air-filled chamber and a centric net-on
      both-sides chamber), single-net (including a sealed air-filled chamber on the top
      side and a net-on-one-side chamber on the bottom side), and eccentric double-net
      (including an eccentric net-on-both-sides chamber and an air-filled chamber).
      They were exquisitely designed after precise calculations of every chamber
      parameters according to the buoyant principle. All of them showed good floating
      ability, although only the latter two TiD systems were selected due to
      appropriate drug release. Compressed riboflavin tablets, consisting of
      riboflavin, lactose, hydroxypropyl methylcellulose (HPMC) and magnesium stearate,
      were prepared with the direct compaction method. All the tablets showed rapid
      drug release though the release was highly hindered by the devices in the TiD
      systems due to the barrier effect of devices and the tablet slurry formation. The
      single-net and double-net TiD systems achieved the cumulative release of 41% and
      62% at 72 h, respectively, along with simultaneously well floating. In vivo long
      term (>72 h) gastric floating function of TiD systems was further demonstrated on
      the rabbit models by the CT investigation. TiD systems are appropriate for oral
      administration of drugs with super long-term floating and controlled release in
      the gastric route.

PMID- 30107219
TI  - Early formulation development of CKD-519, a new CETP inhibitor, for phase 1
      clinical study based on in vitro and in vivo evaluation.
AB  - CKD-519, a potent cholesteryl ester transfer protein (CETP) inhibitor, is a
      clinical candidate being developed for the treatment of dyslipidemia. It is
      considered a Biopharmaceutical Classification System II compound with low
      solubility and high permeability. The objective of this study was to develop
      early formulations focusing on the dissolution rate of the compound to achieve
      dose-dependent exposure. High performance formulation strategies including solid
      dispersion (SD) and a self-microemulsifying drug delivery system (SMEDDS) were
      investigated and their in vivo and in vitro correlations were also evaluated in
      monkeys along with dose optimization in human volunteers. The SD granules were
      prepared in a fluid bed granulator using microcrystalline cellulose and mannitol
      as carriers. Poloxamer 407 and Eudragit E PO were each found to be a suitable
      solubilizing agent and polymer for the improvement of the CKD-519 dissolution
      rate. Pharmacokinetic studies in monkeys showed that the SD tablets exhibited
      better absorption than the SMEDDS in a dose-dependent manner from 1.5 mg to 100
      mg. The mannitol-based SD tablet formulations were bioequivalent. However,
      pharmacokinetics studies in humans showed that the dose was saturable above 100
      mg of CKD-519. This study was performed to determine how to develop early
      formulations for clinical studies and to identify rational formulation
      development strategies for CKD-519 to establish the pharmaceutical proof-of
      concept in humans.

PMID- 30107220
TI  - Impact of blend properties on die filling during tableting.
AB  - Based on characterization of a wide range of fillers and APIs, thirty divergent
      blends were composed and subsequently compressed on a rotary tablet press,
      varying paddle speed and turret speed. The tablet weight variability was
      determined of 20 grab samples consisting of each 20 tablets. Additionally, the
      bulk residence time, ejection force, pre-compression displacement, main
      compression force, die fill fraction and feed frame fill fraction were determined
      during each run. Multivariate data analysis was applied to investigate the
      relation between the process parameters, blend characteristics, product and
      process responses. Blends with metoprolol tartrate as API showed high ejection
      forces. This behavior could be linked to the high wall friction value of
      metoprolol tartrate. The main responses related to the die filling could be
      predicted via a PLS model based on blend characteristics. Tablet weight
      variability was highly correlated with the variability on pre-compression
      displacement and main compression force. A good predictive model for tablet
      weight variability was obtained taking the porosity, wall friction angle,
      flowability, density, compressibility and permeability into account.
      Additionally, turret speed and paddle speed were included in the calibration of
      the model. The applied approach can save resources (material, time) during early
      drug product development.

PMID- 30107221
TI  - Absorption behavior of etilefrine after buccal administration in rats.
AB  - Etilefrine hydrochloride (ET-HCl) is used in the treatment of hypotension. Dosage
      forms of orally administered tablets and parenteral injections are clinically
      available, but exhibit unfavorable characteristics, including cardiac toxicity,
      headaches, and damage at the injection site for the parenteral dosage form, and
      initially high plasma levels, fast elimination, and first-pass effects for its
      oral administration. Therefore, the buccal application of ET-HCl was herein
      investigated as an alternative to conventional administration routes. I.v.,
      intragastric, and buccal administration were performed using rats, and absorption
      features were compared. Buccal application at open conditions for 1 h exhibited
      absolute bioavailability of more than 20%, while the intragastric administration
      gave much lower bioavailability (<10%). The drug residue and drug distribution in
      the oral mucosa were investigated in order to clarify drug transfer behaviors. In
      the application of ET-HCl solution using a cotton ball, higher plasma
      concentrations and their maintenance at higher levels were achieved at 10 mg/kg
      than at 2.5 mg/kg. In addition, absorption was greater with a longer application
      (4 h) than with a shorter application (1 h). Etilefrine (ET) was rapidly absorbed
      using aqueous buffer of pH 9.5 as the solvent. Open application was appropriate
      for achieving and maintaining higher plasma levels. Thus, in the buccal
      application of ET-HCl aqueous droplets, a wide distribution throughout the
      mucosal surface is important for achieving rapid absorption and the maintenance
      of plasma levels. These findings suggested that the buccal application should be
      feasible administration of ET-HCl.

PMID- 30107222
TI  - Intravenous anesthetic-induced calcium dysregulation and neurotoxic shift with
      age during development in primary cultured neurons.
AB  - Anesthetic-induced neurotoxicity in the developing brain is a concern. This
      neurotoxicity is closely related to anesthetic exposure time, dose, and
      developmental stages. Using calcium imaging and morphological examinations in
      vitro, we sought to determine whether intravenous anesthetic-induced direct
      neurotoxicity varies according to different stages of the days in vitro (DIV) of
      neurons in primary culture. Cortical neurons from E17 Wistar rats were prepared.
      On DIV 3, 7, and 13, cells were exposed to the intravenous anesthetics thiopental
      sodium (TPS), midazolam (MDZ), or propofol (PPF), to investigate direct
      neurotoxicity using morphological experiments. Furthermore, using calcium
      imaging, the anesthetic-induced intracellular calcium concentration ([Ca2+]i)
      elevation was monitored in cells on DIV 4, 8, and 13. All anesthetics elicited
      significant [Ca2+]i increases on DIV 4. While TPS (100 MUM) and MDZ (10 MUM) did
      not alter neuronal death, PPF (10 MUM and 100 MUM) decreased the survival ratio
      (SR) significantly. On DIV 8, TPS and MDZ did not elicit [Ca2+]i elevation or SR
      decrease, while PPF still induced [Ca2+]i elevation (both at 10 MUM and 100 MUM)
      and significant SR decrease at 100 MUM (0.76 +/- 0.03; P < 0.05), but not at 10
      MUM (0.91 +/- 0.03). Such anesthetic-induced [Ca2+]i elevation and SR decrease
      were not observed on DIV 13-14 for any of the anesthetic drugs. Our study
      indicates that more caution may be exercised when using PPF compared to TPS or
      MDZ during development.

PMID- 30107223
TI  - Phosphoenolpyruvate carboxykinase cytosolic and mitochondrial isoforms are
      expressed and active during hypoxia in the white shrimp Litopenaeus vannamei.
AB  - Hypoxic zones in marine environments are spreading around the world affecting the
      survival of many organisms. Marine animals have several strategies to respond to
      hypoxia, including the regulation of gluconeogenesis. Phosphoenolpyruvate
      carboxykinase (PEPCK) is a key regulatory enzyme of gluconeogenesis. The
      objective of this work was to study two isoforms of PEPCK, one mitochondrial
      (PEPKC-M) and one cytosolic (PEPCK-C), from the white shrimp Litopenaeus vannamei
      and the response to hypoxia. Both PEPCK isoforms are 72 kDa proteins and have 92%
      identity at the amino acid level. The mitochondrial isoform has a N-terminal
      signal peptide for mitochondrial import. Gene expression and enzymatic activity
      in subcellular fractions were detected in gills, hepatopancreas and muscle in
      normoxic and hypoxic conditions. Expression of PEPCK-C was higher than PEPCK-M in
      all the tissues and induced in response to hypoxia at 48 h in hepatopancreas,
      while the enzymatic activity of PEPCK-M was higher than PEPCK-C in gills and
      hepatopancreas, but not in muscle and also increased in response to hypoxia in
      hepatopancreas but decreased in gills and muscle. During limiting oxygen
      conditions, shrimp tissues obtain energy by inducing anaerobic glycolysis, and
      although gluconeogenesis implies energy investment, due to the need to maintain
      glucose homeostasis, these gluconeogenic enzymes are active with contrasting
      behaviors in the cytosol and mitochondrial cell compartments and appear to be up
      regulated in hepatopancreas indicating this tissue pivotal role in
      gluconeogenesis during the response to hypoxia.

PMID- 30107224
TI  - Using the behavioral flexibility operant task to detect long-term deficits in
      rats following middle cerebral artery occlusion.
AB  - Stroke is a leading cause of death and disability and currently only has one FDA
      approved pharmacological treatment (tissue plasminogen activator), which is only
      administered to a fraction of stroke patients due to contraindications. New
      treatments are desperately needed but most treatments fail in clinical trials,
      even after showing benefit in animal models of stroke. To increase the
      translatability of animal stroke research to humans, sensitive functional
      measures for both the acute and chronic stages in animal models of stroke are
      needed. The objective of this study was to determine the sensitivity of certain
      behavioral tasks, up to seven weeks following occlusion of the middle cerebral
      artery (MCAo) in rats. A battery of behavioral tasks, including rotorod,
      cylinder, and limb-placement, was conducted weekly for seven weeks. Also, a
      behavioral flexibility operant task was introduced at the end of the study to
      measure cognitive deficits. All functional outcome measures showed significant
      differences between stroke and control groups, indicating that these tasks are
      sensitive enough to detect deficits in a long-term MCAo study in rats. This
      provides useful information for those trying to increase translatability in their
      own stroke research by providing long-term sensitive testing paradigms in a
      relevant stroke model.

PMID- 30107226
TI  - The PRISM project: Social withdrawal from an RDoC perspective.
AB  - The PRISM (Psychiatric Ratings using Intermediate Stratified Markers) project was
      funded under the auspices of the European Union Innovative Medicine Initiative
      (EU-IMI) to explore quantitative approaches to the biological and behavioral
      aspects of neuropsychiatric disorders. PRISM focuses specifically on social
      withdrawal, although its principles are applicable to a wide range of disorders.
      This commentary explores some of the major aspects of the PRISM design from the
      perspective of the Research Domain Criteria (RDoC) project initiated by the
      National Institute of Mental Health. PRISM represents an apt exemplar of the
      principles developed in the RDoC framework, with the potential to contribute
      palpable advances in precision diagnosis and innovative approaches to treatment
      development.

PMID- 30107227
TI  - Linear free energy relationship analysis of permeability across
      polydimethylsiloxane (PDMS) membranes and comparison with human skin permeation
      in vitro.
AB  - The aim of the present work is to evaluate the similarity between PDMS membranes
      and human skin in vitro in permeation study by linear free energy relationship
      (LFER) analyses. The values of the permeability coefficient log Kp (cm/s) under
      reliable experimental conditions were collected from the literature for a set of
      94 compounds including both neutral and ionic species, which cover a broad range
      of structural diversity. The values of log Kp (cm/s) have been correlated with
      Abraham descriptors to yield an equation with R2 = 0.952 and SD = 0.38 log units.
      The established LFER model for log Kp (cm/s) across PDMS membranes showed no
      close analogy with that through human skin in vitro. A further critical analysis
      of the coefficients of the LFER models confirmed that the PDMS permeation system
      is a very poor model for human skin permeation.

PMID- 30107225
TI  - Social behavioral phenotyping of the zebrafish casper mutant following embryonic
      alcohol exposure.
AB  - The term Fetal Alcohol Spectrum Disorder (FASD) describes all the deleterious
      consequences of prenatal alcohol exposure. Impaired social behavior is a common
      symptom of FASD. The zebrafish has emerged as a powerful model organism with
      which to examine the effects of embryonic alcohol exposure on social behavior due
      to an innate strong behavior, called shoaling. The relative transparency of the
      embryo also makes zebrafish powerful for cellular analyses, such as
      characterizing neural circuitry. However, as zebrafish develop, pigmentation
      begins to obscure the brain and other tissues. Due to mutations disrupting
      pigmentation, the casper zebrafish strain remains relatively transparent
      throughout adulthood, potentially permitting researchers to image neural circuits
      in vivo, via epifluorescence, confocal and light sheet microscopy. Currently,
      however the behavioral profile of casper zebrafish post embryonic alcohol
      exposure has not been completed. We report that exposure to 1% alcohol from
      either 6 to 24, or 24 to 26 h postfertilization reduces the social behavior of
      adult casper zebrafish. Our findings set the stage for the use of this important
      zebrafish resource in studies of FASD.

PMID- 30107228
TI  - Adjuvant agents enhance round window membrane permeability to dexamethasone and
      modulate basal to apical cochlear gradients.
AB  - Glucocorticoids have direct anti-inflammatory, anti-oxidant and anti-apoptotic
      effects on cochlear hair cells. Cochlear glucocorticoid therapy has gained
      particular attention for its ability to enhance the protection of residual
      hearing following hearing preservation cochlear implantation. Local drug delivery
      methods achieve high drug concentrations within the inner ear fluids but are
      reliant upon diffusion across the round window membrane. Diffusion has been shown
      to demonstrate large individual variability. This study explores the role of
      "adjuvant agents", which when administered with glucocorticoids, enhance inner
      ear absorption and distribution. Guinea pig cochleae were administered either
      dexamethasone alone or in combination with hyaluronic acid, histamine, or
      combination histamine and hyaluronic acid, targeted at the round window membrane.
      Control subjects received saline. Perilymph was sampled from the cochlear apex,
      and basal to apical dexamethasone concentrations recorded with mass spectroscopy.
      Cochleae were harvested, and immunohistochemistry employed to explore
      dexamethasone tissue penetration and distribution. Basal to apical gradients were
      observed along the scala tympani, with higher dexamethasone concentrations
      observed at the cochlear base. Gradients were more pronounced and uniform when
      administered on a hyaluronic acid sponge, while histamine increased absolute
      concentrations reaching the inner ear. Tissue penetration correlated with
      perilymph concentration. Our results demonstrate that adjuvant agents can be
      employed to enhance dexamethasone absorption and distribution in the inner ear,
      thus proposing therapeutic strategies that may enhance steroid facilitated
      hearing protection.

PMID- 30107230
TI  - Identification of Skt11-regulated genes in chondrocytes by integrated
      bioinformatics analysis.
AB  - SKT11, an important tumor suppressor, is a member of the serine/threonine kinase
      family and plays a crucial role in tumor invasion and metastasis by activated
      adenine monophosphate-activated protein kinase (AMPK) and AMPK-related kinase
      proteins. However, few studies have elaborated its regulations of development and
      metabolism of cartilage, as well as skeleton. This study was aimed to investigate
      the role of Stk11-knockout in chondrocyte by bioinformatics analysis. The gene
      expression profiles for Stk11-knockout and wild-type mice were downloaded from
      the Gene Expression Omnibus (GEO) database. A total of 1104 differentially
      expressed genes (DEGs) were identified by Affymetrix Expression Console and
      Transcriptome Analysis Console (TAC) software, including 560 up-regulated and 544
      down-regulated genes. The protein-protein interaction (PPI) networks were built
      by mapping DEGs into STRING, in which hub genes such as Fos, Pdgfrb, Pdgfra,
      Flt1/Vegfr1, Smad3, Mapk14, Twist and Aurkb were further identified. For the up
      regulated genes, PI3K-AKT signaling pathway and Wnt signaling pathway were two
      main pathways in the KEGG analysis, and ossification and extracellular matrix
      organization were involved in the Gene Ontology (GO) analysis. On the other hand,
      the down-regulated genes were mainly involved in systemic lupus erythematosus and
      alcoholism pathways, and B cell receptor signaling pathway and immune system
      process biological processes. MiRNA-9, miRNA-134, miRNA-492, miRNA-224 and miRNA
      142-5p were identified as key regulators in the miRNAs-DEG regulatory network.
      Additionally, OSF2/RUNX2, and NFAT regulated DEGs collectively in the
      transcription factor regulatory network. The results of RT-PCR verified that the
      expression of hub genes, transcription factors and miRNAs in our experiment were
      basically consistent with the microarray hybridization. In this study, we provide
      an insight into the role of Stk11 in chondrocyte and identify novel genes related
      to Stk11.

PMID- 30107229
TI  - Transcriptome characterization and gene expression analysis related to
      chemoreception in Trichogramma chilonis, an egg parasitoid.
AB  - Chemoreception is critical for the survival of insects. Insects have a variety of
      behavioral responses, such as mating, host searching and ovipositing, in response
      to different odor signals detected in their living environment. Trichogramma
      chilonis, an egg parasitoid, acts as an efficient and effective biocontrol
      reagent for many agricultural and forestry insect pests in many parts of China.
      However, little is known about the molecular mechanism of the olfaction-evoked
      behavior in T. chilonis. In the present study, we conducted transcriptome
      profiling analysis of T. chilonis based on the Illumina high-throughput
      sequencing platform in order to explore differences of chemoreception between
      male and female T. chilonis. In this study, a total of 85 chemosensory genes were
      identified from transcriptomic data, including 45 odorant receptors (ORs), 22
      odorant binding proteins (OBPs), 14 ionotropic receptors (IRs), 2 sensory neuron
      membrane proteins (SNMPs) and 2 chemosensory proteins (CSPs). From the analysis
      of the transcriptome, most of the candidate olfactory genes had similar
      expression levels in males and females, including a few OR and OBP genes
      (TchiOR38, TchiOR39, TchiOR40, TchiOR41, TchiOR42, TchiOR43, TchiOR44, TchiOR45,
      TchiOBP1, TchiOBP4, TchiOBP10, TchiOBP12, TchiOBP18 and TchiOBP19) which showed
      male-biased expression. Some annotated unigenes were chosen randomly to have qRT
      PCR, which verified the correctness of analysis of transcriptome in T. chilonis.
      This is the first study to obtain and identify candidate genes related to
      chemoreception in T. chilonis. Our work lays a solid foundation for related
      future research on the chemosensory system of T. chilonis at the molecular level
      and helps advance the use of T. chilonis as biological control agents.

PMID- 30107232
TI  - Maternal Age at Marriage and Adverse Pregnancy Outcomes: Findings from the India
      Human Development Survey, 2011-2012.
AB  - STUDY OBJECTIVE: This study aimed to examine the association between maternal age
      at marriage and selected pregnancy outcomes: stillbirth, miscarriage, and
      complications during pregnancy, labor, and postpartum period. DESIGN: Cross
      sectional study. SETTING: India. PARTICIPANTS: A total of 35,253 ever-married
      women aged 15-49 years from the second round of the India Human Development
      Survey were used to examine the association between maternal age at marriage and
      stillbirth and miscarriage. Moreover, 14,229 ever-married women who gave birth
      since January 2005 were used to assess the effect of maternal age at marriage on
      pregnancy, labor, and postpartum complications. INTERVENTIONS: Cross-tabulation,
      Pearson's chi2 test, and binary logistic regression were performed for the
      analyses of the study data. MAIN OUTCOME MEASURES: Stillbirth, miscarriage, and
      complications during pregnancy, labor, and postpartum period. RESULTS: Bivariate
      association showed significant differences in women's pregnancy outcomes
      according to their age at marriage. Multivariate logistic regression analyses
      revealed that after controlling for relevant demographic characteristics, the
      likelihood of stillbirth (adjusted odds ratio [AOR], 1.12; P < .05), miscarriage
      (AOR, 1.15; P < .01), pregnancy complications (AOR, 1.24; P < .01), and postnatal
      complications (AOR, 1.32; P < .01) were significantly higher among the women who
      married at 14 years or younger than those married at the age of 18 years or
      later. However, the current study did not show any significant association
      between the women who married at 15-17 years and the pregnancy outcomes except
      for postnatal complications (AOR, 1.12; P < .05) in adjusted analyses.
      CONCLUSION: This study showed that early maternal age at marriage substantially
      increases the risk of adverse pregnancy outcomes, which suggests strengthening of
      existing laws and policies to increase age at marriage of girls, and effort
      should be made to improve health status of married adolescents.

PMID- 30107231
TI  - Unusual Cause of Pediatric Vaginal Bleeding: Infantile Capillary Hemangioma of
      the Cervix.
AB  - BACKGROUND: The differential diagnosis for pediatric prepubertal vaginal bleeding
      is wide. Rare etiologies include vascular malformations and tumors, such as
      infantile hemangiomas (IHs), which validate the usefulness of exam under
      anesthesia, vaginoscopy, and tissue diagnosis. CASE: We report a case of an IH in
      a 6-year-old girl causing vaginal bleeding requiring transfusion. Vaginoscopy
      revealed a cervical IH of less than 1 cm. Expectant management and oral
      propranolol were successful management options. SUMMARY AND CONCLUSION: Rare,
      even small soft tissue tumors such as IH can lead to impressive blood loss via
      vaginal bleeding. Accurate tissue diagnosis and a multidisciplinary approach are
      essential to planning safe, effective treatment, and follow-up.

PMID- 30107233
TI  - Assessment of detailed conformations suggests strategies for improving cryoEM
      models: Helix at lower resolution, ensembles, pre-refinement fixups, and
      validation at multi-residue length scale.
AB  - We find that the overall quite good methods used in the CryoEM Model Challenge
      could still benefit greatly from several strategies for improving local
      conformations. Our assessments primarily use validation criteria from the
      MolProbity web service. Those criteria include MolProbity's all-atom contact
      analysis, updated versions of standard conformational validations for protein and
      RNA, plus two recent additions: first, flags for cis-nonPro and twisted peptides,
      and second, the CaBLAM system for diagnosing secondary structure, validating
      Calpha backbone, and validating adjacent peptide CO orientations in the context
      of the Calpha trace. In general, automated ab initio building of starting models
      is quite good at backbone connectivity but often fails at local conformation or
      sequence register, especially at poorer than 3.5 A resolution. However, we show
      that even if criteria (such as Ramachandran or rotamer) are explicitly restrained
      to improve refinement behavior and overall validation scores, automated
      optimization of a deposited structure seldom corrects specific misfittings that
      start in the wrong local minimum, but just hides them. Therefore, local problems
      should be identified, and as many as possible corrected, before starting
      refinement. Secondary structures are confusing at 3-4 A but can be better
      recognized at 6-8 A. In future model challenges, specific steps being tested
      (such as segmentation) and the required documentation (such as PDB code of
      starting model) should each be explicitly defined, so competing methods on a
      given task can be meaningfully compared. Individual local examples are presented
      here, to understand what local mistakes and corrections look like in 3D, how they
      probably arise, and what possible improvements to methodology might help avoid
      them. At these resolutions, both structural biologists and end-users need
      meaningful estimates of local uncertainty, perhaps through explicit ensembles.
      Fitting problems can best be diagnosed by validation that spans multiple
      residues; CaBLAM is such a multi-residue tool, and its effectiveness is
      demonstrated.

PMID- 30107234
TI  - 3D micro structural analysis of human cortical bone in paired femoral diaphysis,
      femoral neck and radial diaphysis.
AB  - Human bone is known to adapt to its mechanical environment in a living body. Both
      its architecture and microstructure may differ between weight-bearing and non
      weight-bearing bones. The aim of the current study was to analyze in three
      dimensions, the morphology of the multi-scale porosities on human cortical bone
      at different locations. Eight paired femoral diaphyses, femoral necks, and radial
      diaphyses were imaged using Synchrotron Radiation uCT with a 0.7 um isotropic
      voxel size. The spatial resolution facilitates the investigation of the
      multiscale porosities of cortical bone, from the osteonal canals system down to
      the osteocyte lacunar system. Our results showed significant differences in the
      microstructural properties, regarding both osteonal canals and osteocytes
      lacunae, between the different anatomical locations. The radius presents
      significantly lower osteonal canal volume fraction and smaller osteonal canals
      than the femoral diaphysis or neck. Osteocytes lacunae observed in the radius are
      significantly different in shape than in the femur, and lacunar density is higher
      in the femoral neck. These results show that the radius, a non-weight-bearing
      bone, is significantly different in terms of its microstructure from a weight
      bearing bone such as the femur. This implies that the cortical bone properties
      evaluated on the femoral diaphysis, the main location studied within the
      literature, cannot be generalized to other anatomical locations.

PMID- 30107235
TI  - The Sounds of Grief.

PMID- 30107236
TI  - Evaluation of the Implementation of a Multicomponent Intervention to Improve
      Health Care Provider Communication About Human Papillomavirus Vaccination.
AB  - OBJECTIVE: To evaluate the relative use, usefulness, and facilitators and
      barriers to use as perceived by providers of 5 different components in a human
      papillomavirus vaccine communication intervention-which was found to be effective
      at improving human papillomavirus vaccination rates. METHODS: Four serial surveys
      of 108 providers (doctor of medicine, nurse practitioner, or doctor of
      osteopathic medicine) from intervention clinics involved in the study assessed
      the use and usefulness of the 5 communication intervention components during a 12
      month period. RESULTS: Survey response rates were 79% to 86%. The fact sheet (64%
      77%) and motivational interviewing techniques (MI; 86%) were the most used
      components-use was sustained during the 12-month period. These components also
      were perceived as somewhat or very useful by most providers, and this perceived
      usefulness increased over time (very or somewhat useful at end of study, 97% fact
      sheet, 98% MI, respectively). Although fewer providers reported using the Web
      site (15%-42%), or disease images (6%-17%), when these were used, most providers
      (67%-87%) felt they were somewhat or very useful. The decision aid was not used
      frequently (17%-41% of providers), and 43% of providers felt it was not very or
      not at all useful. Facilitators and barriers were identified for each component.
      The fact sheet and MI were perceived as the easiest to integrate into the clinic
      workflow. CONCLUSIONS: The fact sheet and MI were the most used and most useful
      intervention components. Both were easy to integrate into clinic workflow, and
      their use was sustained over time. Dissemination of similar interventions in the
      future should focus on these 2 specific components.

PMID- 30107237
TI  - Gene dosage and coexpression with endoplasmic reticulum secretion-associated
      factors improved the secretory expression of alpha-galactosidase.
AB  - The alpha-galactosidases, which can catalyze the removal of alpha-1,6-linked
      terminal galactose residues from galactooligosaccharide materials, have good
      potential for industrial applications. The high-level and efficient secretion of
      the alpha-galactosidases into the extracellular space has greatly simplified the
      downstream bioengineering process, facilitating their bioapplications. In this
      study, the effects of gene dosage and endoplasmic reticulum secretion-associated
      factors (ERSAs) on the secretory expression of an alpha-galactosidase gene
      derived from a Aspergillus oryzae strain were investigated by constructing
      multicopy expression cassettes and coexpressing the alpha-galactosidase gene with
      ERSAs. With the increase in the gene copy-number in the host genome, the
      expression of GalA was improved. However, the secretory expression level was not
      linearly related to the copy number. When the number was higher than four copies,
      the expression level of GalA gene declined. The ERSAs factors HAC1, PDI, and Ero1
      improved the secretory expression of alpha-galactosidase, while Hsp40 inhibited
      its secretion. After methanol-induced expression in a bench-top bioreactor,
      Pichia recombinants carrying four copies of GalA genes reached 3520 U/mL in the
      supernatant of the culture. We further optimized the parameters for alpha
      galactosidase to hydrolyze two types of galactooligosaccharides: raffinose and
      stachyose. This study has fulfilled the scale-up production of alpha
      galactosidase, thus facilitating its industrial applications.

PMID- 30107238
TI  - Resveratrol alleviates ethanol-induced neuroinflammation in vivo and in vitro:
      Involvement of TLR2-MyD88-NF-kappaB pathway.
AB  - Excessive ethanol (EtOH) intake affects cognitive function and leads to permanent
      learning and memory deficits. EtOH-induced neuroinflammation plays an important
      role in EtOH neurotoxicity. Studies have shown that EtOH activates microglia and
      induces an inflammatory response. Resveratrol (Rsv) is a natural polyphenol found
      in a wide variety of plants and fruits, and produces the neuroprotective and anti
      inflammatory effects in the central nervous system. However, effect of Rsv on
      EtOH-induced neuroinflammation is still unknown. We investigated the anti
      inflammatory effect of Rsv in the context of EtOH-induced neurotoxicity and the
      molecular mechanisms potentially involved in the effect. The results showed that
      treatment of rats with Rsv prevented the deficits of spatial reference memory
      induced by EtOH and mitigated EtOH-induced neuroinflammation by inhibiting
      microglial activation and decreasing the levels of inflammatory cytokines
      including interleukin-1beta, interleukin-6 and tumor necrosis factor alpha. The
      further studies indicated that Rsv reduced TLR2 expression in vivo and in vitro,
      and downregulated expression of myeloid differentiation primary response 88
      (MyD88) and phosphorylation of nuclear factor kappaB (NF-kappaB). These data
      demonstrate that Rsv alleviates the ethanol-induced neuroinflammation via
      inhibition of TLR2-MyD88-NF-kappaB signal pathway.

PMID- 30107239
TI  - The optimization of home oxygen weaning in premature infants trial: Design,
      rationale, methods, and lessons learned.
AB  - Improved survival among preterm infants has led to an increase in diagnosis of
      chronic lung disease and infants discharged home from the NICU on supplemental
      oxygen. Despite this increased prevalence, no clearly defined guidelines for the
      management of home oxygen therapy (HOT) exist. This lack of consensus leads to
      significant variability in the duration of home oxygen therapy and a general
      paucity of evidence-based practice. Our team has identified recorded home oxygen
      therapy (RHO) as a potential new resource to guide clinical decision making in
      the outpatient pulmonology clinic. By recording extended O2 saturation data
      during the weaning process, RHO has the potential to save cost and improve the
      processes of HOT management. Our team is currently supporting a prospective,
      multi-center, randomized, controlled trial of RHO guided HOT weaning with the
      aims of determining effect upon duration of HOT, perceived parent quality of life
      and effect upon growth and respiratory outcomes. We plan to randomize 196 infants
      into one of two study arms evaluating standard HOT management versus RHO guided
      oxygen weaning. Our primary outcomes are total HOT duration and parental quality
      of life. This trial represents an unprecedented opportunity to test a novel home
      monitoring intervention for weaning within a vulnerable yet quickly growing
      population. If effective, the use of RHO may provide clinicians a tool for safe
      weaning.

PMID- 30107240
TI  - A Novel Approach to Management of Angular Pregnancies: A Case Series.
AB  - Cornual, interstitial, and angular pregnancies are terms that are often used
      interchangeably in both the literature and clinical setting to describe various
      ectopic pregnancies. The diagnosis of these pregnancies can be difficult, and
      fear of disrupting an intrauterine pregnancy can cause hesitation during
      evaluation and management. In our 2 cases, a combination of transvaginal and 3
      dimensional ultrasound images provided assistance in the accurate diagnosis of
      angular ectopic pregnancies. Traditional management of these pregnancies includes
      a wedge resection for pregnancy resolution. In this set of 2 cases, we describe a
      unique surgical approach to resolve these pregnancies using operative
      hysteroscopy.

PMID- 30107241
TI  - Cost-Effectiveness and Cost-Utility of Internet-Delivered Exposure Therapy for
      Fibromyalgia: Results From a Randomized, Controlled Trial.
AB  - : Fibromyalgia (FM) is a prevalent and debilitating chronic pain disorder
      associated with a substantial economic burden. Although there are several studies
      investigating the effectiveness of psychological treatments such as cognitive
      behavioral therapy for FM, studies on cost-effectiveness are scarce. The aim of
      the present study was to investigate the cost-effectiveness of Internet-delivered
      exposure therapy (iExp) for FM. We used health economic data from a recently
      conducted randomized, controlled trial, where 140 participants were randomized to
      either iExp or a waitlist control (WLC) condition. Economic data were collected
      at pre-treatment, post-treatment, and at the 1-year follow-up. Treatment
      effectiveness in relation to costs were analyzed using both a societal
      perspective (including all direct and indirect costs) and a health care unit
      perspective (including only the direct treatment costs). Bootstrapped net benefit
      regression analyses were also conducted, comparing the difference in costs and
      effects between iExp and WLC, within different willingness-to-pay scenarios.
      Results showed that the incremental cost-effectiveness ratio was -$15,295,
      indicating that iExp was highly cost-effective as each successfully treated case
      (treatment responder) was associated with a substantial net reduction in costs.
      The robustness of the results was tested in 2 different sensitivity analyses,
      where iExp remained cost-effective, even in a willingness-to-pay-scenario of $0.
      We conclude that iExp is a cost-effective treatment that generates large societal
      cost savings. PERSPECTIVE: Health-economic evaluations of psychological
      interventions for FM are scarce. This study is a cost-effectiveness analysis of
      Internet-delivered exposure therapy for patients with FM. Results showed that
      iExp was highly cost-effective compared with no treatment, where each
      successfully treated case generated a substantial societal cost saving.

PMID- 30107242
TI  - Risk of Pain and Gastrointestinal Complaints at 6Months After Elective Abdominal
      Surgery.
AB  - : The incidence of chronic postoperative abdominal pain (CPAP) after abdominal
      surgery is substantial and decreases overall quality of life. One in 3 patients
      report pain-related interference with mood, sleep, and enjoyment of life and 12%
      visit the emergency department for pain-related symptoms. Previous studies lack
      data on preoperative health and pain status or are limited by small patient
      samples. The aim of this study was to assess risk factors for CPAP and
      gastrointestinal complaints 6 months after surgery. A prospective cohort study
      was performed including patients undergoing an elective laparotomy or laparoscopy
      at a tertiary referral center. Relevant patient, pain, surgical, and medical data
      as well as the Gastrointestinal Symptom Rating Scale (GSRS) were assessed before,
      during, and after hospital stay and at the outpatient clinic until 6 months after
      discharge. Linear and logistic regression analysis were used to assess risk
      factors. Of 518 included patients, 184 (36%) had CPAP. The median GSRS score was
      5 (interquartile range = 3-10). The presence of preoperative pain for <3 months
      (odds ratio [OR] = 2.69, P = .016) or >3 months (OR = 3.99, P = .000), use of
      opioid analgesia preoperatively (OR = 3.54, P = .001), severe adhesions
      underneath the incision (OR = 1.63, P = .040), and the numeric rating scale pain
      score on postoperative day 2 (OR = 1.23, P = .004) independently increased the
      risk for chronic abdominal pain. Chronic pancreatitis as indication for surgery
      (B = 4.20, P = .03), >=3 previous abdominal operations (B = 1.03, P = .03),
      presence of pain >3 months before surgery (B = 1.61, P < .01), upper
      gastrointestinal tract as the anatomic location of surgery (B = 1.43, P = .03),
      and a higher preoperative GSRS score (B = .36, P < .01) independently increased
      the GSRS score 6 months after surgery. The duration and severity of preoperative
      pain and more severe acute postoperative pain were the most relevant risk factors
      for CPAP. The number of operations and the anatomic location of the operation
      showed to be important risk factors for increasing the number of gastrointestinal
      complaints. PERSPECTIVE: This prospective observational study shows the incidence
      and risk factors for CPAP after major abdominal surgery. Preoperative pain
      related factors were associated with the occurrence of CPAP.

PMID- 30107243
TI  - Botulinum toxin type A or selective neurotomy for treating focal spastic muscle
      overactivity?
AB  - OBJECTIVE: To discuss the effectiveness, indications, limitations and side
      effects of botulinum toxin type A and selective neurotomy for treating focal
      spastic muscle overactivity to help clinicians choose the most appropriate
      treatment. METHODS: Expert opinion based on scientific evidence and personal
      experience. RESULTS: Botulinum toxin type A can decrease muscle tone in different
      types of spastic muscle overactivity, which allows for treating a large variety
      of spastic patterns with several etiologies. The toxin effect is sometimes
      insufficient to improve functional outcome and is transient, thereby requiring
      repeated injections. Selective neurotomy is a permanent surgical treatment of the
      reflex component of the spastic muscle overactivity (spasticity) that is
      effective for spastic equinovarus foot. The neurotomy provides a greater and more
      constant reduction in spasticity. However, the long-lasting effect on the non
      reflex muscle overactivity, especially dystonia, is doubted. The effectiveness,
      clinical indications, advantages, side effects and limitations of both techniques
      are discussed. CONCLUSION: Botulinum toxin type A has the highest level of
      evidence and the largest range of indications. However, the botulinum toxin
      effect is reversible and seems less effective, which supports a permanent
      surgical treatment such as selective neurotomy, especially for the spastic foot.
      Further research is needed to compare the effect of botulinum toxin type A and
      selective neurotomy for the different types of spastic muscle overactivity and
      clinical patterns.

PMID- 30107244
TI  - A novel insertion and deletion mutation in the BHLHA9 underlies polydactyly and
      mesoaxial synostotic syndactyly with phalangeal reduction.
AB  - Mesoaxial syndactyly is characterized by fusion of the central digits. The
      disorder segregates in autosomal recessive pattern and mapped on human chromosome
      17p13.3. Homozygous missense mutations in the BHLHA9 have been reported to cause
      mesoaxial synostotic syndactyly with phalangeal reduction (MSSD). In the present
      study, we have investigated a family segregating mesoaxial synostotic syndactyly
      with phalangeal reduction (MSSD) in autosomal recessive manner. Genotyping using
      microsatellite markers followed by Sanger sequencing revealed a homozygous
      deletion and insertion mutation (NM_001164405: c.252_270delinsGCA;
      p.(Phe85Glufs*108)) in the BHLHA9 gene in affected individuals of the family.
      This study reports the first frameshift mutation in the BHLHA9 causing mesoaxial
      synostotic syndactyly and phalangeal reduction.

PMID- 30107245
TI  - Efficacy of Aeschynomene indica L. leaves for wound healing and isolation of
      active constituent.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the aerial parts
      of Aeschynomene indica L. (AIL) have been used for wound healing, and to treat
      urinary tract infection, hepatitis, enteritis, dysentery, nyctalopia,
      conjunctivitis, urticaria, and furuncle. However, no scientific investigation has
      been conducted on its wound healing potential. AIM OF THE STUDY: To investigate
      the effects of AIL extract on wound healing, isolate the active constituent and
      reveal the possible mechanism of enhancing wound healing. MATERIALS AND METHODS:
      The circular excision wound healing model was used to evaluate in vivo wound
      healing activity. Hematoxylin and eosin staining was applied to assess
      inflammatory cells infiltration, angiogenesis, fibroblast proliferation, collagen
      synthesis, collagen remodeling, and skin appendages generation. Sirius red-picric
      acid staining was employed for quantitative analysis of the ratio of collagen
      I/III. Immunohistochemical staining for CD68, CCR7 (CD197), CD163, TGF-beta1 and
      alpha-SMA was performed to determine macrophages phenotypes transition (M1-to-M2)
      and prove the scar-improving effect of AIL on wound healing. RESULTS: We
      successfully isolated the active constituent (Sub-Fr0.2) for wound healing from
      AIL extract, circular excision wound healing experiment and hematoxylin & eosin
      staining showed Sub-Fr0.2 has a significant promoting effect on wound healing.
      Results of sirius red-picric acid staining demonstrated a reduced ratio of
      collagen I/III in the Sub-Fr0.2 group as compared with the vehicle group.
      Immunohistochemical staining for CD68, CCR7 (CD197), and CD163 in the Sub-Fr0.2
      group exhibited an elevated speed of macrophages transiting from M1 phenotype to
      M2 phenotype, when compared with the vehicle group. Besides, the expression of
      TGF-beta1 and alpha-SMA were inhibited on wounds treated with the ointment
      containing Sub-Fr0.2. CONCLUSION: Leaves of AIL and its active constituent (Sub
      Fr0.2) effectively promoted wound healing and reduced scar formation, this
      efficacy might be exerted by accelerating macrophages phenotypes transition and
      inhibiting TGF-beta1 and alpha-SMA expression.

PMID- 30107247
TI  - Morphometric Measurements of the C1 Lateral Mass with Congenital Occipitalization
      of the Atlas.
AB  - OBJECTIVE: Unfamiliarity with the morphometry of the assimilated C1 lateral mass
      (C1LM) could make screw placement dangerous. In the present study, we defined the
      morphometric dimensions of the occipitalized C1LM to provide surgeons with
      valuable information for preoperative planning. METHODS: Thin-slice computed
      tomography scanning data from 131 patients with occipitalization of the atlas
      (OA) and 50 control cases were imported into Mimics software for analysis. The
      widths and heights of the C1LM were fully measured in the different planes. The
      ideal inward angulation and the safe maximum cephalic angulation of C1 screw
      trajectory were evaluated. RESULTS: Except for the medial height, all the widths
      and heights of C1LM were significantly shorter in the OA group than those in the
      control group. The ideal inward angle (alpha) was significantly larger in the OA
      group (23.8 degrees  +/- 8.3 degrees ) than that (15.3 degrees  +/- 3.8 degrees )
      in the control group; the corresponding screw length was also significantly
      longer in the OA group (20.9 +/- 2.9 mm). The safe maximum cephalic angles (beta)
      of the screw trajectory did not reach a significant difference between the 2
      groups. All the widths and heights were shorter in the females than those in the
      males. The alpha angle also did not reach a significant difference between the
      sexes; however, the beta angles in the males (35.9 degrees  +/- 10.4 degrees )
      was significantly larger than that in the females (32.0 degrees  +/- 9.4 degrees
      ). CONCLUSIONS: Although the hypoplastic C1LM brings limitations to screw
      insertion to some extent, it is still broad enough to accommodate a screw safely
      in both female and male patients. Considering the irregularity of the C1LM in
      patients with OA, the preoperative imaging assessment is critical, and C1LM screw
      placement should be performed individually.

PMID- 30107246
TI  - Artepillin C, drupanin, aromadendrin-4'-O-methyl-ether and kaempferide from
      Brazilian green propolis promote gastroprotective action by diversified mode of
      action.
AB  - ETHOPHARMACOLOGICAL RELEVANCE: The propolis is extensively used in folk medicine
      in natura or to prepare pharmaceutical formulations since ancient time to improve
      health or prevent diseases, among them gastrointestinal disorders. Aiming to
      contribute in the scientific validation about the popular use of Brazilian Green
      propolis (BGP) against gastritis and gastric ulcer, this work evaluated the
      antiulcer potential of isolated compounds from BGP, three prenylated p-coumaric
      acid derivatives and two flavonoids, respectively named: 3,5 diprenyl-4
      hydroxycinnamic acid (artepillin C) (1), 3-prenyl-4-dihydroxycinnamoiloxy
      cinnamic acid (baccharin) (2), 3-prenyl-4-hydroxycinnamic acid (drupanin) (3),
      aromadendrin-4'-O-methyl-ether (4) and kaempferide (5). MATERIAL AND METHODS: The
      compounds were characterized by nuclear magnetic resonance and mass spectrometry.
      Their gastroprotective effects were evaluated against ethanol/HCl- and
      indomethacin-induced ulcer in mice. Further, histological, histochemical,
      oxidative and inflammatory parameters were analyzed at ulcerated tissue. Acid
      antisecretory activities also were also assessed. RESULTS: Compound 2 did not
      reduce the ethanol/HCl- induced ulcer at 30 mg/kg (p.o), whereas the minimum oral
      gastroprotective doses of 1, 3, 4 and 5 were 0.3, 0.3, 3 and 3 mg/kg,
      respectively. Besides, these compounds prevented ethanol/HCl-induced ulcer by
      intraperitoneal route, as well as indomethacin-induced ulcer by oral route. The
      gastroprotection was accompanied by normalization of superoxide dismutase,
      catalase and glutathione-S-transferase activities and reduction in
      myeloperoxidase activity. Moreover, the compounds 4 and 5 increased the gastric
      mucin content and 1 reduced TNF amount. Furthermore, 1, 3, 4 and 5 decreased
      volume, pH, total acidity and pepsin activity of the gastric juice from rats.
      CONCLUSIONS: Together, our findings showed a diversified mode of action elicited
      by 1, 3, 4 and 5 on the gastroprotection and contribute to explain the anti-ulcer
      activity reported for BGP.

PMID- 30107248
TI  - Management of Concomitant Moyamoya Disease, Arterial Venous Malformation, and
      Intracranial Aneurysm: Case Illustration, Literature Review, and Management
      Algorithm.
AB  - BACKGROUND: Moyamoya disease (MMD), arterial venous malformations (AVMs), and
      intracranial aneurysms are distinct cerebrovascular disease processes that most
      commonly occur in isolation. The literature on the treatment algorithm of each
      individual condition is well established. An association between MMD and
      intracranial aneurysms is also known, but MMD in association with AVM is rare.
      CASE DESCRIPTIONS: The authors discuss various dilemmas in the multimodality
      management of these conditions when they coexist with an illustrative case of a
      46-year-old woman who presented following a stroke, with 1) left-sided MMD, 2)
      left-sided frontal AVM, and 3) an aneurysm arising from the A1 segment of the
      right anterior cerebral artery. These were managed respectively by 1) the left
      external carotid artery to M2 segment of middle cerebral artery bypass using an
      autologous radial artery graft and left indirect superior temporal artery
      encephaloduroarteriosynangiosis, 2) stereotactic radiosurgery, and 3)
      endovascular coiling of the aneurysm. Three years following intervention,
      cerebral angiography showed a patent bypass, complete obliteration of the AVM,
      and no residual filling of the coiled aneurysm. CONCLUSIONS: Our strategy of
      surgical revascularization for MMD, radiosurgery for AVM, and endovascular
      coiling for aneurysm resulted in a positive long-term clinical outcome. In view
      of the rarity of the condition, the authors propose a management algorithm for
      such patients.

PMID- 30107249
TI  - Identification of another primordial CD80/86 molecule in rainbow trout: Insights
      into the origin and evolution of CD80 and CD86 in vertebrates.
AB  - In mammals, the binding of distinct costimulatory ligands CD80 and CD86 to their
      receptors is essential for optimal T cell activation. Previous studies have shown
      that only a single CD80/86 gene exists in rainbow trout (termed rtCD80/86A) and
      other teleost fish, suggesting that CD80 and CD86 arose by gene duplication in
      the tetrapod branch, after the separation of fish and tetrapods. However, in this
      study, another CD80/86 gene has been cloned from rainbow trout, termed
      rtCD80/86B. The sequence identity between trout CD80/86 is significantly higher
      than that between CD80 and CD86 in tetrapods, indicating that CD80 and CD86
      underwent divergent evolution in vertebrates, especially in tetrapods. Gene
      synteny analyses showed that the CD80 and CD86 genes are closely located in the
      same chromosome in tetrapods. However, CD80/86 genes are located in two distinct
      chromosomes in rainbow trout and Atlantic salmon, suggesting that salmonid
      CD80/86 genes arose by the salmonid-specific whole-genome duplication (WGD)
      event. Expression analysis showed that rtCD80/86A was more abundant and inducible
      than rtCD80/86B in various tissues, indicating the important role of rtCD80/86A
      in trout immunity. Interestingly, we found that head kidney B cells showed higher
      expression level of rtCD80/86A and rtCD80/86B when compared with the other
      leukocytes, suggesting a potential role for trout B cells as antigen-presenting
      cells (APCs).

PMID- 30107250
TI  - Dual oxidases participate in the regulation of hemolymph microbiota homeostasis
      in mud crab Scylla paramamosain.
AB  - Dual oxidases (DUOXs) were originally identified as NADPH oxidases (NOXs), found
      to be associated with the reactive oxygen species (ROS) hydrogen peroxide (H2O2)
      production at the plasma membrane and crucial in host biological processes. In
      this study, SpDUOX1 and SpDUOX2 of mud crab (Scylla paramamosain) were identified
      and studied. Both SpDUOX1 and SpDUOX2 are transmembrane proteins, including an N
      signal peptide region and a peroxidase homology domain in the extracellular
      region, transmembrane regions, and three EF (calcium-binding region) domains, a
      FAD-binding domain, and a NAD binding domain in the intracellular region. The
      SpDUOXs were expressed in all tissues examined, but mainly in hepatopancreas,
      heart, and mid-intestine. The expression of the SpDUOXs in the hemolymph of mud
      crabs was up-regulated after challenge with Vibrio parahemolyticus or LPS. RNA
      interference (RNAi) of the SpDUOXs resulted in reduced ROS production in
      hemolymph. The bacterial count increased in the hemolymph of mud crabs injected
      with SpDUOX1 or SpDUOX2-RNAi, while the bacterial clearance ability of hemolymph
      significantly reduced. At the phylum level, the phyla Bacteroidetes and
      Actinobacteria were significantly increased, while Proteobacteria were
      significantly reduced following SpDUOX2 knockdown. There was a significant
      increase in the relative abundance of the genera Marinomonas, Pseudoalteromonas,
      Shewanella, and Hydrogenoph in SpDUOX2 depleted mud crabs compared with the
      controls. Our current findings therefore indicated that SpDUOXs might play
      important roles in maintaining the homeostasis in the hemolymph microbiota of mud
      crab.

PMID- 30107251
TI  - A non-venomous sPLA2 of a lepidopteran insect: Its physiological functions in
      development and immunity.
AB  - Eicosanoids are oxygenated C20 polyunsaturated fatty acids that mediate various
      physiological processes in insects. Eicosanoid biosynthesis begins with a C20
      precursor, arachidonic acid (5,8,11,14-eicosatetraenoic acid: AA). AA is usually
      released from phospholipids at sn-2 position by catalytic activity of
      phospholipase A2 (PLA2). Although various PLA2s classified into 16 gene families
      (= Groups) are known in various biological systems, few PLA2s are known in
      insects. Only two PLA2s involved in intracellular calcium independent PLA2
      (iPLA2) group have been identified in lepidopteran insects with well known
      eicosanoid physiology. This study reports the first secretory PLA2 (sPLA2) in
      lepidopteran insects. A partial open reading frame (ORF) of PLA2 was obtained by
      interrogating Spodoptera exigua transcriptome. Subsequent 3'-RACE resulted in a
      full ORF (Se-sPLA2A) encoding 194 amino acid sequence containing signal peptide,
      calcium-binding domain, and catalytic site. Phylogenetic analysis indicated that
      Se-sPLA2A was clustered with other Group III sPLA2s. Se-sPLA2A was expressed in
      most larval instars except late last instar. Its expression was inducible by
      immune challenge and juvenile hormone analog injection. RNA interference of Se
      sPLA2A significantly suppressed cellular immunity and impaired larval
      development. These results suggest that non-venomous sPLA2 plays a crucial role
      in immune and developmental processes in S. exigua, a lepidopteran insect.

PMID- 30107252
TI  - Cutoff fluorescence loss for the recovery of incipient carious lesions after
      fluoride application in primary teeth: A clinical study.
AB  - PURPOSE: Early detection and diagnosis of incipient caries are the keys to
      achieving a favorable prognosis. Monitoring of pathological changes based on
      clinical evidence leads to an accurate prognosis. Therefore, this clinical study
      investigated changes in minerals of incipient carious lesions using quantitative
      light-induced fluorescence-digital (QLF-D) after applying professional fluoride
      treatment to children, with improvement of the lesion severity assessed based on
      the fluorescence loss (DeltaF) value obtained using QLF-D. METHODS: This study
      examined 90 incipient enamel lesions on the primary teeth of 27 children aged
      between 4 and 10 years. QLF-D images were obtained before and after the
      application of 1.23% acidulated phosphate fluoride gel for 1 min, and the DeltaF
      values at 0 and 4 weeks (DeltaF(0) and DeltaF(4), respectively) and the recovery
      rates (RDeltaF) of the lesions were evaluated. Receiver operating characteristic
      curve analysis was used to calculate the cutoff DeltaF(0) value at which recovery
      of the lesion with fluoride treatment remained feasible. RESULTS AND CONCLUSION:
      The recovery patterns of DeltaF 4 weeks after fluoride application differed
      depending on the DeltaF(0) values. The incipient lesions with DeltaF(0) values of
      less than -13.00 recovered 4 weeks after fluoride application (P <  0.001) and
      had an average RDeltaF value of 19.27%. The results indicate that a DeltaF(0)
      cutoff value can be determined for predicting the effects of remineralization
      after fluoride application and quantitative prognostic data can be provided to
      patients.

PMID- 30107253
TI  - Evaluation of anti-arthritic potential of Trigonella foenum graecum L.
      (Fenugreek) mucilage against rheumatoid arthritis.
AB  - Rheumatoid arthritis is a chronic inflammatory joint disease characterized by
      synovial proliferation and tissue destruction. Pro-inflammatory cytokines like
      interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) play a key role
      in the disease process and elevate energy expenditure, which further increases
      the joint pain and stiffness. The present study was undertaken to explore the
      anti-arthritic potential of fenugreek mucilage in adjuvant induced arthritic
      rats. In the present study, paw volume was measured on the 7th, 14th and 21st
      day. Finally, animals were anaesthetized; blood samples and tissues were
      collected for the assay of inflammatory enzymes like cyclooxygenase,
      lipoxygenase; evaluated the level of cytokines like IL-6, TNF-alpha, arthritic
      index and rheumatoid factor. Fenugreek mucilage exhibited maximum percentage of
      edema inhibition at a dose of 75 mg/kg on 21st day of adjuvant arthritis. The
      effect was higher than that of standard drug, indomethacin. The activities of
      inflammatory enzymes and concentration of mediators were decreased on treatment
      with fenugreek mucilage. Cytology of synovial fluid showed mild inflammation with
      normal synoviocytes (mesothelial cells) tried to bring back to normal
      characteristics on supplementation with fenugreek mucilage. Based on the
      observations, it can be suggested that fenugreek mucilage possesses promising
      anti-arthritic property and it can be used as a therapeutic agent for arthritis.

PMID- 30107254
TI  - Effect of dietary alanyl-glutamine dipeptide against chronic ammonia stress
      induced hyperammonemia in the juvenile yellow catfish (Pelteobagrus fulvidraco).
AB  - Triplicate groups of juvenile yellow catfish (1.98 +/- 0.01 g) were fed diets
      supplemented with 0% and 1% alanyl-glutamine dipeptide (AGD) for 56 days under
      three ammonia concentrations (0.01, 5.70 and 11.40 mg L-1 total ammonia
      nitrogen). The results showed that ammonia poisoning could induce growth (weight
      gain and specific growth rate) and survival reduction, live ammonia and serum
      malondialdehyde accumulation, and subsequently lead to blood deterioration (serum
      total protein, albumin, globulin, alkaline phosphatase and acid phosphatase
      reduced), oxidative stress (superoxide dismutase and glutathione peroxidase
      activities declined), and induce down-regulation of antioxidant enzymes (SOD, GPX
      and GRX) genes transcription. However, dietary supplemented with 1% AGD could
      mitigate the adverse effect of ammonia poisoning on fish growth performance.

PMID- 30107255
TI  - Differential associations between appendicular and axial marrow adipose tissue
      with bone microarchitecture in adolescents and young adults with obesity.
AB  - Marrow adipose tissue (MAT) in humans is distributed differentially across age
      and skeletal site. We have shown impaired microarchitecture and reduced bone
      strength at appendicular sites in conditions associated with high MAT of the
      axial skeleton in adults (including conditions of over- and undernutrition). Data
      are lacking regarding differences in MAT content of the appendicular versus the
      axial skeleton, and its relationship with bone microarchitecture and strength.
      Furthermore, data are conspicuously lacking in adolescents, a time when
      hematopoietic marrow is progressively converted to fatty marrow. The purpose of
      our study was to examine differential associations between appendicular (distal
      tibia) and axial (lumbar spine) MAT and bone microarchitecture and strength
      estimates of the distal tibia in adolescents with obesity. We hypothesized that
      compared to MAT of the axial skeleton (lumbar spine), MAT of the appendicular
      skeleton (distal tibia) would show stronger associations with bone
      microarchitecture and strength estimates of the appendicular skeleton (distal
      tibia). We evaluated 32 adolescents and young adults (27 females) with obesity;
      with a mean age of 17.8 +/- 2.1 years and median body mass index (BMI) of 41.34
      kg/m2, who underwent dual energy X-ray absorptiometry (DXA) for total fat mass,
      proton MR spectroscopy (1H-MRS) of the distal tibia and 4th lumbar vertebra for
      MAT, high resolution peripheral quantitative computed tomography (HR-pQCT) of the
      distal tibia for volumetric bone mineral density (vBMD) and microarchitecture,
      and micro finite element analysis (FEA) for distal tibial strength estimates.
      Linear correlations between bone parameters and MAT were determined using the
      Spearman or Pearson methods, depending on data distribution. Lumbar spine MAT was
      inversely associated with age (r = -0.36; p = 0.037). Total and trabecular vBMD
      and trabecular number at the distal tibia were inversely associated with MAT at
      the distal tibia (r = -0.39, p = 0.025; r = -0.51, p = 0.003; r = -0.42, p =
      0.015 respectively) but not with lumbar spine MAT (r = -0.19, p = 0.27; r = 
      0.18, p = 0.3; r = 0.005, p = 0.97 respectively). In adolescents and young adults
      with obesity, the associations between MAT and appendicular bone parameters
      differ depending on the site of MAT assessment i.e. axial vs. appendicular.
      Studies evaluating these endpoints in adolescents and young adults with obesity
      should take the site of MAT assessment into consideration.

PMID- 30107256
TI  - People are averse to machines making moral decisions.
AB  - Do people want autonomous machines making moral decisions? Nine studies suggest
      that that the answer is 'no'-in part because machines lack a complete mind.
      Studies 1-6 find that people are averse to machines making morally-relevant
      driving, legal, medical, and military decisions, and that this aversion is
      mediated by the perception that machines can neither fully think nor feel.
      Studies 5-6 find that this aversion exists even when moral decisions have
      positive outcomes. Studies 7-9 briefly investigate three potential routes to
      increasing the acceptability of machine moral decision-making: limiting the
      machine to an advisory role (Study 7), increasing machines' perceived experience
      (Study 8), and increasing machines' perceived expertise (Study 9). Although some
      of these routes show promise, the aversion to machine moral decision-making is
      difficult to eliminate. This aversion may prove challenging for the integration
      of autonomous technology in moral domains including medicine, the law, the
      military, and self-driving vehicles.

PMID- 30107257
TI  - Volumetric development of the zebra finch brain throughout the first 200 days of
      post-hatch life traced by in vivo MRI.
AB  - The first months of life are characterized by massive neuroplastic processes that
      parallel the acquisition of skills and abilities vital for proper functioning in
      later life. Likewise, juvenile songbirds learn the song sung by their tutor
      during the first months after hatching. To date, most studies targeting brain
      development in songbirds exclusively focus on the song control and auditory
      pathways. To gain a comprehensive insight into structural developmental
      plasticity of the entire zebra finch brain throughout the different subphases of
      song learning, we designed a longitudinal study in a group of male (16) and
      female (19) zebra finches. We collected T2-weighted 3-dimensional anatomical
      scans at six developmental milestones throughout the process of song learning,
      i.e. 20, 30, 40, 65, 90 and 120 days post hatching (dph), and one additional time
      point well after song crystallization, i.e. 200 dph. We observed that the total
      brain volume initially increases, peaks around 30-40 dph and decreases towards
      the end of the study. Further, we performed brain-wide voxel-based volumetric
      analyses to create spatio-temporal maps indicating when specific brain areas
      increase or decrease in volume, relative to the subphases of song learning. These
      maps informed (1) that most areas implicated in song control change early, i.e.
      between 20 and 65 dph, and are embedded in large clusters that cover major
      subdivisions of the zebra finch brain, (2) that volume changes between
      consecutive subphases of vocal learning appear highly similar in males and
      females, and (3) that only more rostrally situated brain regions change in volume
      towards later ages. Lastly, besides detecting sex differences in local tissue
      volume that align with previous studies, we uncovered two additional brain loci
      that are larger in male compared to female zebra finches. These volume
      differences co-localize with areas related to the song control and auditory
      pathways and can therefore be associated to the behavioral difference as only
      male zebra finches sing. In sum, our data point to clear heterochronous patterns
      of brain development similar to brain development in mammalian species and this
      work can serve as a reference for future neurodevelopmental imaging studies in
      zebra finches.

PMID- 30107258
TI  - Lingering expectations: A pseudo-repetition effect for words previously expected
      but not presented.
AB  - Prediction can help support rapid language processing. However, it is unclear
      whether prediction has downstream consequences, beyond processing in the moment.
      In particular, when a prediction is disconfirmed, does it linger, or is it
      suppressed? This study manipulated whether words were actually seen or were only
      expected, and probed their fate in memory by presenting the words (again) a few
      sentences later. If disconfirmed predictions linger, subsequent processing of the
      previously expected (but never presented) word should be similar to actual word
      repetition. At initial presentation, electrophysiological signatures of
      prediction disconfirmation demonstrated that participants had formed
      expectations. Further downstream, relative to unseen words, repeated words
      elicited a strong N400 decrease, an enhanced late positive complex (LPC), and
      late alpha band power decreases. Critically, like repeated words, words
      previously expected but not presented also attenuated the N400. This "pseudo
      repetition effect" suggests that disconfirmed predictions can linger at some
      stages of processing, and demonstrates that prediction has downstream
      consequences beyond rapid on-line processing.

PMID- 30107259
TI  - Content-specific codes of parametric auditory working memory in humans.
AB  - Brain activity in frontal regions has been found to represent frequency
      information with a parametric code during working memory delay phases. The mental
      representation of frequencies has furthermore been shown to be modality
      independent in non-human primate electrophysiology and human EEG studies,
      suggesting frontal regions encoding quantitative information in a supramodal
      manner. A recent fMRI study using multivariate pattern analysis (MVPA) supports
      an overlapping multimodal network for the maintenance of visual and tactile
      frequency information over frontal and parietal brain regions. The present study
      extends the investigation of working memory representation of frequency
      information to the auditory domain. To this aim, we used MVPA on fMRI data
      recorded during an auditory frequency maintenance task. A support vector
      regression analysis revealed working memory information in auditory association
      areas and, consistent with earlier findings of parametric working memory, in a
      frontoparietal network. A direct comparison to an analogous dataset of
      vibrotactile parametric working memory revealed an overlap of information coding
      in prefrontal regions, particularly in the right inferior frontal gyrus.
      Therefore, our findings indicate that the prefrontal cortex represents frequency
      specific working memory content irrespective of the modality as has been now also
      revealed for the auditory modality.

PMID- 30107260
TI  - The effects of the dietary supplementation of Echinacea purpurea extract and/or
      vitamin C on the intestinal histomorphology, phagocytic activity, and gene
      expression of the Nile tilapia.
AB  - In this study, the influence of the dietary incorporation of Echinacea purpurea
      (EP) extract and/or vitamin C on the intestinal histomorphology and some
      immunological indices were tested in the Nile tilapia (Oreochromis niloticus
      Linn.). O. niloticus were randomly divided into four groups. The control group G1
      was fed on a basal diet, while the G2 and G3 were fed on basal diets,
      supplemented with EP extract and vitamin C at the doses of 500 mg kg-1 and 400 mg
      kg-1, respectively. Meanwhile, G4 was fed on a basal diet, supplemented with a
      mixture of EP extract and vitamin C. After 28 days of feeding, the intestinal
      tissues were collected for histological observation and immune status, was based
      on an assay for measuring the phagocytic activity. Furthermore, the expression of
      the transforming growth factor-beta 1 (TGF-beta1), interleukin-1beta (IL-1beta),
      and tumor necrosis factor alpha (TNF-alpha) genes was evaluated in intestine and
      head kidney. The results revealed that the G4 successfully surpassed the other
      groups in terms of the heights of intestinal villi, the number of goblet cells
      and intraepithelial lymphocytes (IELs), and the phagocytic activity, followed by
      the G3 and G2. The expression of the IL-1beta and TNF-alpha genes were up
      regulated only in G4 but in the G3 only the expression of the IL-1beta gene was
      up regulated. Hence, EP extract along with vitamin C could be used as a feed
      additive in order to improve the structure of the intestinal mucosal epithelium
      and immune response in tilapia.

PMID- 30107261
TI  - Galactoside-binding lectin in Solen grandis as a pattern recognition receptor
      mediating opsonization.
AB  - Galactoside-binding lectin (galectin) is a type of pathogen recognition molecule
      that occupies an important position in the invertebrate innate immunity system.
      Our previous study has identified a galectin gene in mollusk Solen grandis (SgGal
      1) and illustrated its potential roles in innate immunity. By the functional
      study using recombinant protein and specific antibody, here, we confirmed the
      pivotal roles of SgGal-1 in immune defense of S. grandis. SgGal-1 protein was
      expressed in many tested tissues including gill, mantle, hepatopancreas and
      gonad, except hemocytes and muscle. The recombinant SgGal-1 (rSgGal-1) bound PGN
      and beta-glucan instead of LPS in vitro, and it further caused significant
      agglutination of five different microbes, suggesting SgGal-1 served as a pattern
      recognition receptor (PRR) involved in immune defense of mollusk. Furthermore,
      SgGal-1 recruited hemocytes to encapsulate, which was blocked by anti-rSgGal-1
      serum. In the meantime, rSgGal-1 as well as promoted the phagocytosis of
      hemocytes against Escherichia coli in vitro. All these results suggested that
      SgGal-1 in S. grandis not only acted as a PRR recognizing microbes but also
      directly participated in the process of immune opsonization to protect the host
      from pathogenic infection.

PMID- 30107262
TI  - Comparative transcriptome analysis of Chinese grass shrimp (Palaemonetes
      sinensis) infected with isopod parasite Tachaea chinensis.
AB  - Parasitic isopods negatively affect reproduction and ingestion in several
      commercially important crustaceans; however, little is known about such parasite
      host interactions. Therefore, we performed high-throughput sequencing of cDNA
      samples from Chinese grass shrimp Palaemonetes sinensis infected by parasitic
      isopod Tachaea chinensis and a non-infected control. We randomly assembled
      46,858,882 and 41,110,746 clean reads from the parasitized and control groups,
      respectively. From these, we identified 1323 differentially expressed genes
      (DEGs) (p < 0.05), of which 702 were up-regulated and 621 were down-regulated
      after T. chinensis infection, respectively. The up-regulated genes were enriched
      in 'ribosome', 'purine metabolism', and 'pyrimidine metabolism' signalling
      pathways, suggesting altered host nucleotide metabolite levels, possibly through
      the action of intracellular parasites transported by T. chinensis. Additionally,
      14 representative DEGs involved in reproduction were down-regulated after
      parasitisation, indicating T. chinensis causes cascading effects in P. sinensis.
      Overall, parasitisation appeared to affect host immune response, metabolism, and
      gonadal development. In conclusion, the present study improves our understanding
      on the molecular mechanisms underlying interactions between isopod parasites and
      their crustacean hosts.

PMID- 30107263
TI  - Directed strain evolution restructures metabolism for 1-butanol production in
      minimal media.
AB  - Engineering a microbial strain for production sometimes entails metabolic
      modifications that impair essential physiological processes for growth or
      production. Restoring these functions may require amending a variety of non
      obvious physiological networks, and thus, rational design strategies may not be
      practical. Here we demonstrate that growth and production may be restored by
      evolution that repairs impaired metabolic function. Furthermore, we use genomics,
      metabolomics and proteomics to identify several underlying mutations and
      metabolic perturbations that allow metabolism to repair. Previously, high titers
      of butanol production were achieved by Escherichia coli using a growth-coupled,
      modified Clostridial CoA-dependent pathway after all native fermentative pathways
      were deleted. However, production was only observed in rich media. Native
      metabolic function of the host was unable to support growth and production in
      minimal media. We use directed cell evolution to repair this phenotype and
      observed improved growth, titers and butanol yields. We found a mutation in pcnB
      which resulted in decreased plasmid copy numbers and pathway enzymes to balance
      resource utilization. Increased protein abundance was measured for biosynthetic
      pathways, glycolytic enzymes have increased activity, and adenosyl energy charge
      was increased. We also found mutations in the ArcAB two-component system and
      integration host factor (IHF) that tune redox metabolism to alter byproduct
      formation. These results demonstrate that directed strain evolution can enable
      systematic adaptations to repair metabolic function and enhance microbial
      production. Furthermore, these results demonstrate the versatile repair
      capabilities of cell metabolism and highlight important aspects of cell
      physiology that are required for production in minimal media.

PMID- 30107264
TI  - Does CBT for anxiety-related disorders alter suicidal ideation? Findings from a
      naturalistic sample.
AB  - BACKGROUND: Anxiety disorders commonly co-occur with suicidal ideation (SI). To
      our knowledge, no studies have reported on the baseline prevalence of SI and the
      reduction in SI in a naturalistic sample receiving cognitive behavior therapy
      (CBT) for anxiety-related disorders. METHODS: Participants (n = 355) recruited
      from an anxiety specialty clinic reported SI at pre-, mid-, and post-CBT.
      Multilevel mixed effects logistic regression models compared differences in SI
      endorsement over Time. RESULTS: Posttraumatic stress disorder (PTSD) and social
      anxiety disorder (SAD) were associated with significantly elevated baseline SI
      relative to specific phobia. PTSD and unspecified anxiety-related disorders were
      associated with significant reductions in SI, whereas reductions in SAD, GAD,
      OCD, and panic disorder did not reach significance. Rates of new onset and
      exacerbation of SI were low. DISCUSSION: CBT for anxiety disorders was associated
      with significant reductions in SI over time, with no evidence for exacerbation of
      suicide risk. Clinical implications are discussed, as well as future research
      directions to further understand the effect of anxiety disorder treatments on SI.

PMID- 30107265
TI  - The link between immunity, autoimmunity and endometriosis: a literature update.
AB  - Endometriosis (EMS), an estrogen-dependent inflammatory disorder affects
      approximately 5-10% of the general female population of reproductive age and 20
      90% of women with pelvic pain and infertility. Many immunological factors are
      known to contribute significantly to the pathogenesis and pathophysiology of EMS,
      and both chronic local inflammation and autoantibodies in EMS shares many
      similarities with autoimmune diseases (AD). However, the autoimmune etiology in
      EMS remains controversial, and its evidence on autoimmune basis may be limited.
      Here we aim to review the current understanding between autoimmunity and EMS to
      provide important knowledge to develop future potential immunomodulatory therapy
      for the treatment of EMS.

PMID- 30107266
TI  - Monogenic polyautoimmunity in primary immunodeficiency diseases.
AB  - Primary immunodeficiency diseases (PIDs) consist of a large group of genetic
      disorders that affect distinct components of the immune system. PID patients are
      susceptible to infection and non-infectious complications, particularly
      autoimmunity. A specific group of monogenic PIDs are due to mutations in genes
      that are critical for the regulation of immunological tolerance and immune
      responses. This group of monogenic PIDs is at high risk of developing
      polyautoimmunity (i.e., the presence of more than one autoimmune disease in a
      single patient) because of their impaired immunity. In this review, we discuss
      the mechanisms of autoimmunity in PIDs and the characteristics of
      polyautoimmunity in the following PIDs: IPEX; monogenic IPEX-like syndrome; LRBA
      deficiency; CTLA4 deficiency; APECED; ALPS; and PKCdelta deficiency.

PMID- 30107267
TI  - Does cyclophosphamide still play a role in glomerular diseases?
AB  - Cyclophosphamide is a prodrug that is converted to inactive carboxy
      cyclophosphamide, acrolein and phosphoramide mustard, an agent that adds alkyl
      groups to oxygen and nitrogen atoms of guanine, one of the four nitrogen bases
      that form the DNA nucleotides, causing DNA cross-links and introducing DNA
      breaks. These cytotoxic and mutagenic effects mainly occur in proliferating
      cells. Repair mechanisms may prevent DNA damage in quiescent cells, but they may
      be insufficient to contrast the side effects of cyclophosphamide if high doses of
      the drug are used. Most adverse events are dose- and age-dependent. Phosphoramide
      mustard can cause bone marrow toxicity, gonadal toxicity, and may favor the
      development of leukemia, bladder cancer and other types of malignancy. Acrolein
      can produce hemorrhagic cystitis and even bladder fibrosis when given for
      prolonged periods. A number of precautional measures should be taken to prevent
      these untoward events. In particular, long-term administration and high doses of
      cyclophosphamide should be avoided whenever possible. Today the indications to
      cyclophosphamide in glomerular diseases are more restricted than in the past, but
      the drug is still used as a steroid-sparing agent in steroid-sensitive minimal
      change disease and focal segmental glomerulosclerosis. In membranous nephropathy,
      cyclophosphamide, alternated or associated with corticosteroids, proved to be
      beneficial in obtaining remission of nephrotic syndrome and preserving renal
      function. Cyclophosphamide is considered as a first-line treatment for rapidly
      progressive glomerulonephritis and the hectic phases of lupus nephritis. In
      conclusion, cyclophosphamide is a cheap drug that may be useful in a number of
      glomerular diseases but it may lead to severe side effects. A close monitoring of
      blood count and clinical conditions, as well as low cumulative doses of
      cyclophosphamide are strongly recommended when using the drug in patients with
      renal diseases.

PMID- 30107268
TI  - Neuroimaging hippocampal subfields in schizophrenia and bipolar disorder: A
      systematic review and meta-analysis.
AB  - The hippocampus is a complex structure consisting of subregions with specialized
      cytoarchitecture and functions. Magnetic resonance imaging (MRI) studies in
      psychotic disorders show hippocampal subfield abnormalities, but affected regions
      differ between studies. We here present an overview of hippocampal anatomy and
      function relevant to psychosis, and the first systematic review and meta-analysis
      of MRI studies of hippocampal subfield morphology in schizophrenia and bipolar
      disorder. Twenty-one MRI studies assessing hippocampal subfield volumes or shape
      in schizophrenia or bipolar disorder were included (n 15-887 subjects). Nine
      volumetric group comparison studies (total n = 2593) were included in random
      effects meta-analyses of group differences. The review showed mixed results, with
      volume reductions reported in most subfields in schizophrenia and bipolar
      disorder. Volumetric studies using ex-vivo based image analysis templates
      corresponded best with the shape studies, with CA1 as the most affected region.
      The meta-analyses showed volume reductions in all subfields in schizophrenia and
      bipolar disorder compared to healthy controls (all p < .005; schizophrenia: d =
      0.28-0.49, bipolar disorder: d = 0.20-0.35), and smaller left CA2/3 and right
      subiculum in schizophrenia than bipolar disorder. In conclusion, the hippocampal
      subfields appear to be differently affected in psychotic disorders. However, due
      to the lack of control for putative confounders such as medication, alcohol and
      illicit substance use, and illness stage, the results from the meta-analysis
      should be interpreted with caution. Methodological subfield segmentation
      weaknesses should be addressed in future studies.

PMID- 30107270
TI  - A bone-targeting delivery system carrying osteogenic phytomolecule icaritin
      prevents osteoporosis in mice.
AB  - Targeting delivery system has been widely used in packaging drugs for medical
      therapies attributed to its high efficiency and efficacy. A Traditional Chinese
      Medicine (TCM) formula consisting of Herba Epimedii has previously been shown to
      effectively treat postmenopausal osteoporosis. We have subsequently found that
      icaritin, which was a flavonoid isolated from both Herba Epimedii and its serum
      metabolites after oral administration, inhibited the adipogenic capacity of bone
      mesenchymal stem cells (BMSCs) while promoted their osteogenesis. However,
      previous pharmacokinetic analyses have shown that icaritin had a short half-life
      in blood and only trace amounts of the molecule reach the bone tissue. To
      overcome this limitation, we developed a bone-targeting liposome containing an
      oligopeptide of eight aspartate residues (Asp8), which had previously been shown
      to specifically target the bone, encapsulating icaritin. In vivo, we found that
      the Asp8-icaritin-liposome enhanced bone formation in ovariectomized mice
      compared to an icaritin-liposome control lacking the Asp8 moiety. Through in
      vitro mechanistic studies we further found that icaritin inhibited adipogenesis
      through an Akt/GSK-3beta/beta-catenin signaling pathway. Taken together, our
      study shows that Asp8-liposome as a bone-targeting delivery system is effective
      to carry an osteogenic phytomolecule for facilitating and enhancing its
      therapeutic effects on the prevention of estrogen depletion-induced osteoporosis.

PMID- 30107269
TI  - FKBP5 polymorphisms and hypothalamic-pituitary-adrenal axis negative feedback in
      major depression and obsessive-compulsive disorder.
AB  - Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) have both
      been linked to abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis.
      Polymorphisms in the genes involved in HPA axis activity, such as FKBP5, and
      their interactions with childhood trauma have been associated with stress-related
      mental disorders. Our goal was to study the role of FKBP5 genetic variants in HPA
      axis negative feedback regulation as a possible risk factor for different mental
      disorders such as MDD and OCD, while controlling for childhood trauma, anxiety
      and depressive symptoms. The sample included 266 participants divided into three
      groups: 1) MDD (n = 89 [n = 73 melancholic; n = 3 atypical]), 2) OCD (n = 51; 39%
      with comorbid MDD [n = 13 melancholic; n = 7 atypical]) and 3) healthy controls
      (n = 126). Childhood trauma, trait anxiety and depressive symptoms were assessed.
      HPA negative feedback was analyzed using the dexamethasone suppression test ratio
      (DSTR) after administration of 0.25 mg of dexamethasone. Twelve SNPs in the FKBP5
      gene were selected for genotyping. Multiple linear regressions, after adjusting
      for the covariates considered, showed a reduced DSTR in individuals with the
      rs9470079-A variant that was significant after correction for multiple testing.
      Childhood trauma did not moderate the association between the rs9470079 and DSTR.
      Our results support the evidence that FKBP5 genetic variation could lead to
      abnormal HPA axis negative feedback independent of diagnosis. Therefore, this
      association can be identified as a transdiagnostic feature, offering an
      interesting opportunity to identify patients with higher stress vulnerability.
      Further studies focusing on the influence of FKBP5 on measurable biological
      endophenotypes are needed.

PMID- 30107271
TI  - Paradox of PEGylation in fabricating hybrid nanoparticle-based nicotine vaccines.
AB  - Polyethylene glycol (PEG) has long been used in nanoparticle-based drug or
      vaccine delivery platforms. In this study, nano-nicotine vaccines (NanoNicVac)
      were PEGylated to different degrees to investigate the impact of PEG on the
      immunological efficacy of the vaccine. Hybrid nanoparticles with various degrees
      of PEGylation (2.5%-30%) were assembled. It was found that 30% PEGylation
      resulted in a hybrid nanoparticle of a compromised core-shell structure. A higher
      concentration of PEG also led to a slower cellular uptake of hybrid nanoparticles
      by dendritic cells. However, increasing the quantity of the PEG could effectively
      reduce nanoparticle aggregation during storage and improve the stability of the
      hybrid nanoparticles. Subsequently, nicotine vaccines were synthesized by
      conjugating nicotine haptens to the differently PEGylated hybrid nanoparticles.
      In both in vitro and in vivo studies, it was found that a nicotine vaccine with
      20% PEGylation (NanoNicVac 20.0) was significantly more stable than the vaccines
      with lower PEGylation. In addition, NanoNicVac 20.0 induced a significantly
      higher anti-nicotine antibody titer of 3.7 +/- 0.6 * 104 in mice than the other
      NanoNicVacs with lower concentrations of PEG. In a subsequent pharmacokinetic
      study, the lowest brain nicotine concentration of 34 +/- 11 ng/g was detected in
      mice that were immunized with NanoNicVac 20.0. In addition, no apparent adverse
      events were observed in mice immunized with NanoNicVac. In summary, 20%
      PEGylation confers NanoNicVac with desirable safety, the highest stability, and
      the best immunological efficacy in mice.

PMID- 30107272
TI  - Poly(propylacrylic acid)-peptide nanoplexes as a platform for enhancing the
      immunogenicity of neoantigen cancer vaccines.
AB  - Cancer vaccines targeting patient-specific tumor neoantigens have recently
      emerged as a promising component of the rapidly expanding immunotherapeutic
      armamentarium. However, neoantigenic peptides typically elicit weak CD8+ T cell
      responses, and so there is a need for universally applicable vaccine delivery
      strategies to enhance the immunogenicity of these peptides. Ideally, such
      vaccines could also be rapidly fabricated using chemically synthesized peptide
      antigens customized to an individual patient. Here, we describe a strategy for
      simple and rapid packaging of peptide antigens into pH-responsive nanoparticles
      with endosomal escape activity. Electrostatically-stabilized polyplex
      nanoparticles (nanoplexes) can be assembled instantaneously by mixing decalysine
      modified antigenic peptides and poly(propylacrylic acid) (pPAA), a polyanion with
      pH-dependent, membrane destabilizing activity. These nanoplexes increase and
      prolong antigen uptake and presentation on MHC-I (major histocompatibility
      complex class I) molecules expressed by dendritic cells, resulting in enhanced
      activation of CD8+ T cells. Using an intranasal immunization route, nanoplex
      vaccines inhibit formation of lung metastases in a murine melanoma model.
      Additionally, nanoplex vaccines strongly synergize with the adjuvant alpha
      galactosylceramide (alpha-GalCer) in stimulating robust CD8+ T cell responses,
      significantly increasing survival time in mice with established melanoma tumors.
      Collectively, these findings demonstrate that peptide/pPAA nanoplexes offer a
      facile and versatile platform for enhancing CD8+ T cell responses to peptide
      antigens, with potential to complement ongoing advancements in the development of
      neoantigen-targeted cancer vaccines.

PMID- 30107274
TI  - An orthopaedic surgeon's guide to ultrasound imaging of the healthy, pathological
      and postoperative shoulder.
AB  - Ultrasound (US) imaging is an efficient, easy to use and inexpensive tool
      allowing for facilitated diagnosis and management of the painful shoulder. It
      remains primarily used by radiologists and rheumatologists, despite having shown
      excellent diagnostic accuracy when used by different medical specialities in
      their office-based consultation. It also has advantages over other imaging
      modalities in the evaluation of the postoperative shoulder for rotator cuff
      integrity and correct anchor and suture placement, as well as rotator cuff
      analysis following arthroplasty. Integration of US imaging into the orthopaedic
      surgeon's toolbox can be aided by a basic understanding of US principles,
      accompanied by a guide outlining basic techniques for evaluation of the healthy,
      pathological and postoperative shoulder as well as US-guided treatment
      possibilities.

PMID- 30107273
TI  - Direct loading of CTL epitopes onto MHC class I complexes on dendritic cell
      surface in vivo.
AB  - Dendritic cell (DC)-based cytotoxic T lymphocyte (CTL) epitope vaccines are
      effective to induce CTL responses but require complex ex vivo DC preparation and
      epitope-loading. To take advantage of DC-based epitope vaccines without involving
      the ex vivo procedures, we aimed to develop carriers to directly load CTL
      epitopes onto DCs in vivo. Here, we first engineered a carrier consisting of a
      hydrophilic polypeptide, immune-tolerant elastin-like polypeptide (iTEP) and a
      substrate peptide of matrix metalloproteinases-9 (sMMP). The iTEP was able to
      solubilize CTL epitopes. CTL epitopes were connected to the carrier, iTEP-sMMP,
      through sMMP so that the epitopes can be cleaved from the carrier by MMP-9. iTEP
      sMMP was found to release its epitope payloads in the DC culture media, which
      contained MMP-9 released from DCs. iTEP-sMMP allowed for the direct loading of
      CTL epitopes onto the surface MHC class I complexes of DCs. Importantly, iTEP
      sMMP resulted in greater epitope presentation by DCs both in vitro and in vivo
      than a control carrier that cannot directly load epitopes. iTEP-sMMP also induced
      2-fold stronger immune responses than the control carrier. To further enhance the
      direct epitope-loading strategy, we furnished iTEP-sMMP with an albumin-binding
      domain (ABD) and found the new carrier, ABD-iTEP-sMMP, had greater lymph node
      (LN) accumulation than iTEP-sMMP. ABD-iTEP-sMMP also resulted in greater immune
      responses than iTEP-sMMP by 1.5-fold. Importantly, ABD-iTEP-sMMP-delivered CTL
      epitope vaccine induced stronger immune responses than free CTL epitope vaccine.
      Taken together, these carriers utilized two physiological features of DCs to
      realize direct epitope-loading in vivo: the accumulation of DCs in LNs and MMP-9
      released from DCs. These carriers are a potential substitute for DC-based CTL
      epitope vaccines.

PMID- 30107275
TI  - Medial knee osteoarthritis precedes medial meniscal posterior root tear with an
      event of painful popping.
AB  - BACKGROUND: An event of painful popping is a highly predictive clinical sign of
      medial meniscal posterior root tears (MMPRTs) in middle-aged to older patients.
      There are lacks of studies about the prevalence of a painful popping event and
      the condition of the medial compartment at the time of popping event in MMPRTs.
      HYPOTHESIS: We hypothesized that most of MMPRTs with a single painful popping
      event would show pre-existed pathologic medial meniscal extrusion (MME) and
      articular cartilage degeneration, and larger contact area of medial femoral
      condyle to medial tibial plateau could affect the MME. In addition, MME would be
      correlated with knee osteoarthritis. PATIENTS AND METHODS: Thirty-eight patients
      (mean age 58.5+/-10.5) who had painful popping within 3 weeks were included. On
      MRIs, absolute MME, relative percentage of extrusion (RPE), MME-medial femoral
      condyle (MFC)/medial tibial condyle (MTC) at 0 degrees  ratio, and medial
      compartments' Modified Outerbridge Scale (MOS) were evaluated. Kellgren-Lawrence
      (K-L) grade was also assessed. RESULTS: The MME parameters including absolute
      MME, RPE, and the ratio between MME and MFC/MTC at 0 degrees  were 2.9+/-1.2mm,
      22.0+/-10.3%, and 3.2+/-1.3. Patients who with MOS and K-L grade>=2 were 33
      (86.8%) and 32 (84.2%). Patients were divided into MME>=3mm (group G, n=20) and
      MME<3mm (groupL, n=18). The MME parameters were significantly greater in group G
      than group L (all, p<0.001). The group G had worse osteoarthritis progression in
      terms of MOS and K-L grade than the group L (p=0.035 and 0.077, respectively)
      MME>=3mm showed significantly association with MOS>=3 (p=0.045). DISCUSSION: More
      than 80% of MMPRT patients with an event of painful popping within 3 weeks showed
      that medial compartment degeneration preceded the event of popping. Therefore,
      identification of MME and articular cartilage degeneration at the time of painful
      popping in MMPRTs could be helpful when the surgeon determines the most
      appropriate treatment. LEVEL OF EVIDENCE: IV, Case-series.

PMID- 30107276
TI  - Calcium Phosphate Cement loaded with 10% vancomycin delivering high early and
      late local antibiotic concentration in vitro.
AB  - BACKGROUND: Antibiotics impregnated calcium phosphate cement (CPC) has emerged as
      a local treatment of osteomyelitis. However, there is no study investigating the
      optimal concentrations of vancomycin (VCM) included in CPC to obtain prolonged
      drug release (>=8 weeks) and also with enough compressive strength (>the normal
      cancellous bone, 11MPa) for osteomyelitis therapy. Therefore, we bring forward
      two questions: 1) Was antibiotic activity of the eluates correlated to the load
      of antibiotics within the cement? 2) Were the mechanical properties of CPC
      affected by VCM-loading? HYPOTHESIZED: There was an optimal concentrations of
      vancomycin (VCM) loaded in CPC which could provide sufficient effective
      antibacterial time (>=8 weeks) and enough compressive strength (>11MPa).
      MATERIALS AND METHODS: CPC specimens were obtained by incorporating different
      doses (weigh ratios of 0%, 5%, 10%, 15%, 20%, 25 and 30%) of injectable VCM into
      CPC. The antibacterial effect of released VCM solution against Staphylococcus
      aureus was assessed by inhibition ring assays. The physicochemical properties
      such as compressive strengths were characterized and compared among these
      specimens. RESULTS: Drug release profiles showed only 5 and 10% VCM-loaded CPC
      displayed a long enough drug release time (at least 8 weeks) and maintained the
      eluate concentrations (>4MUg/mL) with effective antibacterial ability. The
      concentration of VCM in 10% group at 8th week was twice higher than 5% group.
      Compressive strength test showed that the proportional increase of VCM/CPC ratios
      resulted in a significant decrease of compressive strength (r=-0.906, p<0.001).
      CONCLUSION: 10% VCM-loaded CPC offered the optimal physicochemical properties and
      drug releasing profile and appears as the most suitable concentration for
      clinical use. LEVEL OF EVIDENCE: III.

PMID- 30107277
TI  - Do trapeziometacarpal prosthesis provide better metacarpophalangeal stability
      than trapeziectomy and ligamentoplasty?
AB  - BACKGROUND: No surgical management is better than another regarding functional
      recovery for trapeziometacarpal joint osteoarthritis. Metacarpophalangeal (MCP)
      hyperextension, directly due to the shortening of thumb height, appears to be a
      factor of poor prognosis. HYPOTHESIS: MCP hyperextension can be corrected by
      implantation of a trapeziometacarpal prosthesis (TMP), as opposed to
      trapeziectomy and ligamentoplasty (TL), and pinch strength is greater with TMP in
      this indication. MATERIAL AND METHODS: Sixty-nine patients (41 TMP and 28 TL)
      were retrospectively evaluated. The following were evaluated: pain, mobility of
      the metacarpophalangeal joints, palmar grip and pinch strength. Thumb height was
      measured on radiographs as a post/preoperative ratio. RESULTS: The mean follow-up
      was 20 months (6-38). The TMP group showed greater reduction of the
      metacarpophalangeal hyperextension in all hyperextension groups, especially
      hypertension >30 degrees , compared with TL. The TMP group provided significant
      greater pinch strength in all the subgroups with preoperative MCP hyperextension.
      Patient with postoperative MCP hyperextension had a significant lower grip and
      pinch strength compared with patient without MCP hyperextension. Radiographic
      analysis showed that thumb height changes were related to the degree of
      preoperative hyperextension. Postoperatively, patients with postoperative MCP
      hyperextension had a significant lower thumb height than patient without MCP
      hyperextension. DISCUSSION: Metacarpophalangeal hyperextension appears to be a
      factor of poor prognosis for surgical treatment of trapeziometacarpal
      osteoarthritis when it is not managed. TMP provides better metacarpophalangeal
      stabilization by restoring thumb length and would avoid surgery on the
      metacarpophalangeal joint. TMP may be recommended in patients having symptomatic
      trapeziometacarpal joint osteoarthritis and MCP joint hyperextension. LEVEL OF
      EVIDENCE: III, retrospective observational case control study.

PMID- 30107279
TI  - Evaluation of two web-based interventions in reducing the stigma of suicide.
AB  - Suicide is more highly stigmatized than most mental health conditions; however,
      no interventions have aimed to modify the stigma of suicide in the general
      population. This study tested the efficacy of two brief web-based interventions
      psychoeducation and interpersonal exposure-in reducing suicide-related stigma in
      a student/community sample. A sample of 266 adults completed baseline measures of
      suicide-related stigma, were randomized into one of three conditions
      (psychoeducation, interpersonal exposure, control), in which they browsed an
      assigned website for twenty minutes, and completed post-intervention and one
      month follow-up stigma measures. Results indicated that the two interventions
      were more efficacious than the control in reducing suicide-related stigma; this
      effect was accentuated for individuals without prior exposure to suicide.
      Although future research is needed to understand the mechanisms of change and the
      generalizability of these findings, it is possible that web-based interventions
      could be a cost- and time-effective avenue of targeting the widespread stigma of
      suicide.

PMID- 30107278
TI  - Medial malleolus fractures: A biomechanical comparison of tension band wiring
      fixation methods.
AB  - BACKGROUND: This study compared the biomechanical properties of three different
      fixation methods of tension band wirings, used in the treatment of medial
      malleolus fractures. The first method used an innovative "handmade bent pin" for
      cerclage fixation. The second method used a U-shaped K-wire to attach the
      cerclage to the medial tibial cortex. These two novel fixation techniques were
      compared with the traditional tension band wiring technique which is fixated to
      the bone by a screw. HYPOTHESIS: Novel fixation techniques of tension band wiring
      provide stable fixation. MATERIAL AND METHODS: In this study 27 artificial bone
      models, which medial malleolus fractures were simulated on, were used. Using an
      electromechanical test device, the force required to pull out each implant was
      assessed and compared. RESULTS: This study found that; while handmade bent
      pinning resulted averagely 840.25N (range: 647-1066+/-118.72) and U-shaped K-wire
      fixation was 381.71N (range: 176-651+/-150.2) pull out strength, traditional
      tension band wiring indicated 871.33N (range: 549-1008+/-137.74) pull out
      strength. DISCUSSION: Handmade bent pinning method provide similar results with
      traditional tension band wiring. Therefore, in suitable cases, it may be an
      acceptable alternative to traditional tension band wiring techniques when
      treating malleolar fractures. Although the outcomes of U-shaped K-wire fixation
      indicated lower than other two groups, the outcomes were comparable with the
      literature. So while performing tension band wiring, both handmade fixation
      systems may be used in certain cases. For Orthopaedic surgeons, it is better to
      know and think about these alternative handmade pinning systems created from
      simple K-wires during the surgery if needed. LEVEL OF EVIDENCE: IV, Biomechanical
      trial.

PMID- 30107280
TI  - A plea from EUCAST for standardization of disc susceptibility testing
      antimicrobial codes.

PMID- 30107281
TI  - Are third-generation cephalosporins associated with a better prognosis than
      amoxicillin/clavulanate in patients hospitalized in the medical ward for
      community-onset pneumonia?-Author's reply.

PMID- 30107282
TI  - A diagnostic evaluation of a molecular assay used for testing and treating
      anorectal chlamydia and gonorrhoea infections at the point-of-care in Papua New
      Guinea.
AB  - OBJECTIVES: Papua New Guinea has among the highest prevalences of sexually
      transmissible infections (STIs) globally with no services able to accurately test
      for anorectal Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)
      infections. Here we prospectively evaluated the diagnostic performance of a
      molecular CT/NG assay used at the point-of-care (POC) with the aim of enhancing
      anorectal STI screening and same-day treatment. METHODS: Men who have sex with
      men, transgender women and female sex workers taking part in Papua New Guinea's
      first large-scale biobehavioural study were enrolled and asked to provide a self
      collected anorectal swab for POC GeneXpert CT/NG testing. Same-day treatment was
      offered if positive. A convenience sample of 396 unique and randomly selected
      samples were transported to Australia for comparison using the Cobas 4800 CT/NG
      test (Roche Molecular Diagnostics, Pleasanton, CA, USA). RESULTS: A total of 326
      samples provided valid results by Cobas whereas 70 samples provided invalid
      results suggesting inhibition. The positive, negative and overall percentage
      agreements of GeneXpert CT/NG for the detection of C. trachomatis were 96.7% (95%
      CI 92.3%-98.9%), 95.5% (95% CI 91.3%-98.0%) and 96.0% (95% CI 93.3%-97.8%), and
      for N. gonorrhoeae were 93.0% (95% CI 86.1%-97.1%), 100.0% (95% CI 98.3%-100.0%)
      and 97.8% (95% CI 95.6%-99.1%), respectively. CONCLUSIONS: The overall rate of
      agreement between the GeneXpert and Cobas CT/NG assays was high with 96.0% for C.
      trachomatis and 97.8% for N. gonorrhoeae. Results from this study data suggest
      that the GeneXpert CT/NG assay is suitable for testing self-collected anorectal
      specimens at the POC and that same-day treatment was feasible.

PMID- 30107283
TI  - Phase 1 study of MEDI3902, an investigational anti-Pseudomonas aeruginosa PcrV
      and Psl bispecific human monoclonal antibody, in healthy adults.
AB  - OBJECTIVES: MEDI3902 is a bivalent, bispecific human immunoglobulin G1kappa
      monoclonal antibody that binds to both the Pseudomonas aeruginosa PcrV protein
      involved in host cell cytotoxicity and the Psl exopolysaccharide involved in P.
      aeruginosa colonization and tissue adherence. MEDI3902 is being developed for the
      prevention of nosocomial P. aeruginosa pneumonia in high-risk patients. METHODS:
      This phase 1 dose-escalation study (NCT02255760) evaluated the safety,
      pharmacokinetics, antidrug antibody (ADA) responses and ex vivo anticytotoxicity
      and opsonophagocytic killing activities of MEDI3902 after a single intravenous
      infusion in healthy adults aged 18 to 60 years. Fifty-six subjects were
      randomized in a 3:1 ratio to receive 250, 750, 1500 or 3000 mg of MEDI3902 or
      placebo and followed for 60 days afterwards. RESULTS: Treatment-emergent adverse
      events (TEAEs) were mild or moderate in severity; no serious TEAEs were observed.
      The most common TEAEs were infusion-related reactions. MEDI3902 exhibited
      approximately linear pharmacokinetics across the 250, 750 and 1500 mg doses and
      nonlinear pharmacokinetics between the 1500 and 3000 mg doses. One subject in the
      3000 mg group tested positive for ADA on day 61 and had a lower MEDI3902 serum
      concentration from days 43 to 61 than ADA-negative subjects. Serum
      anticytotoxicity antibody concentrations and opsonophagocytic killing activity
      were correlated with MEDI3902 serum concentrations across all doses. CONCLUSIONS:
      Phase 1 study results of MEDI3902 in healthy subjects support further evaluation
      of its safety and efficacy in subjects at risk for P. aeruginosa pneumonia.

PMID- 30107284
TI  - Contraindicated drug-drug interactions associated with oral antimicrobial agents
      prescribed in the ambulatory care setting in the United States.
AB  - OBJECTIVES: Antimicrobial agents are commonly used in ambulatory care settings.
      Our objective was to examine national-level patterns of contraindications between
      oral antibacterial or antifungal agents and patients' other oral medications in
      the US ambulatory care setting. METHODS: This cross-sectional study included
      multiple year pooled data (2003-2011) from the National Ambulatory Medical Care
      Survey and the National Hospital Ambulatory Medical Care Survey (NHAMCS
      Outpatient Department). Visits by adults (age >=18 years) in ambulatory settings
      in the United States who were prescribed oral antibacterial or antifungal agents
      were evaluated for potential drug-drug interaction (DDI) contraindications.
      Findings with relative standard error >30% or unweighted sample size <30 were not
      reported because these were deemed unreliable estimates. RESULTS: From 2003 to
      2011, there were 1 235 000 outpatient visits (proportion = 0.52%; 95% confidence
      interval (CI), 0.29-0.74) in which a patient was prescribed an antimicrobial
      agent associated with a contraindicated DDI. The most prevalent antimicrobials
      with contraindicated combination among outpatients were simultaneous use of
      macrolide-containing products (erythromycin or clarithromycin) with statin
      medication-containing products (simvastatin or lovastatin) (841 864 visits,
      proportion = 1.91%; 95% CI, 0.96-2.86). The next most common combination was use
      of fluoroquinolones with antiarrhythmic agents (amiodarone, sotalol, quinidine or
      procainamide) (365 622 visits, proportion = 0.19%; 95% CI, 0.06-0.32).
      CONCLUSIONS: Providers should be aware of potential contraindicated DDIs when
      prescribing antibiotics, especially macrolides and fluoroquinolones.

PMID- 30107285
TI  - The "Happy-Mums" website dedicated to the perinatal period: Evaluation of its
      acceptability by parents and professionals.
AB  - OBJECTIVE: Pregnancy and childbirth are associated with new needs for mothers,
      especially an eagerness for information. The aim of this study was to evaluate
      whether the Happy-Mums.be website meets the expectations and needs of its future
      users. DESIGN: After the development of the Happy-Mums.be website, it was
      submitted to parents and professionals and evaluated by an online survey, which
      consisted of the third round of an ongoing Delphi survey. SETTING AND
      PARTICIPANTS: The panel involved in the survey included parents (both mothers and
      fathers) and professionals (health professionals and early childhood
      professionals, orbiting mothers of children aged 0-2 years). FINDINGS: Twenty
      eight parents and professionals participated in the third round of the Delphi
      survey. The participants indicated that Happy-Mums.be was useful and easy to use.
      They attributed a mean score of 8 out of 10 for the content, design and quality
      of the information on the Happy-Mums.be website. The majority of participants
      said that they would recommend the website both during pregnancy and the
      postnatal period. CONCLUSIONS: Happy-Mums.be meets the needs and expectations of
      parents and professionals in terms of both content and design. More specifically,
      the quality of the information found on Happy-Mums.be was judged to be
      significantly better than the information found on other websites.

PMID- 30107286
TI  - Prevalence and predictors of food insecurity among pregnant women: A cross
      sectional study in Qazvin Province, Iran.
AB  - INTRODUCTION: Food insecurity is associated with adverse health consequences in
      women, especially pregnant ones. Present study is aimed to investigate prevalence
      and predictors of food insecurity among pregnant women. METHOD: A cross-sectional
      study was conducted on 394 pregnant women in Qazvin during November 2016-May
      2017. The Household Food Insecurity Access Scale (HFIAS) was used to assess food
      insecurity among pregnant women. Besides, the relationship of demographic,
      midwifery and socioeconomic factors was investigated using Chi-squared and
      logistic regression tests. Then, the obtained data were analyzed in Stata-12
      software at the significance level of 0.05. FINDINGS: Nearly 44% of the
      participants had food insecurity. In multivariate analysis, only husbands'
      unemployment and unwanted pregnancy were associated with food insecurity; thus,
      the chance of food insecurity among women with unemployed husband was higher than
      the women with employed husband by 4.7 times [OR (95% CI) = 4.69(1.64, 13.42)].
      Furthermore, the probability of food insecurity among the participants with
      unwanted pregnancy was twice more than those with wanted pregnancy [OR (95% CI) =
      2.07(1.14, 3.74)]. CONCLUSION: Unemployed husband and unwanted pregnancy are
      related to food insecurity among pregnant women. Nevertheless, due to the nature
      of this study, it was not possible to clearly specify the path of such a
      relationship. To reduce food insecurity among pregnant women, it is essential to
      take all the necessary measures for providing financial supports for pregnant
      women through different ways in order to reduce the stress and worries caused by
      financial burden of pregnancy, and to improve nutrition quality and eating
      behaviours among pregnant women.

PMID- 30107287
TI  - Associations between improved care during the second stage of labour and maternal
      and neonatal health outcomes in a rural hospital in Bangladesh.
AB  - OBJECTIVE: To evaluate the efficacy of care in the second stage of labour with a
      package of interventions that included (1) maintaining the birthing position
      according to the woman's choice, (2) adopting a spontaneous pushing technique and
      (3) using a support person, to reduce maternal and neonatal complications.
      DESIGN: Used the data collected from two cohorts- before and after an initiative
      to improve care during the second stage of labour. SETTING: A rural hospital in
      Bangladesh where 90-100 deliveries are conducted monthly and cesarean section
      provision is not available. PARTICIPANTS: One thousand and fifty-one singleton
      pregnancies who attended the hospital for giving birth in the first stage of
      labour before full dilatation of the cervix and with cephalic presentation.
      MEASUREMENTS AND FINDINGS: Data were collected through a structured checklist and
      questionnaire completed by research assistants; and also retrieved from hospital
      case record files, and the ongoing demographic surveillance system database.
      Coverage of adopting the upright or lateral position in the post-intervention
      period increased to 76% from about 1% in the pre-intervention period, and the
      spontaneous pushing technique increased to 97% from 77% in the same period. The
      odds of combined maternal and neonatal complications decreased by 46% between pre
      and post-intervention periods (odds ratio: 0.54, 95% confidence interval: 0.43
      0.70). Frequency of episiotomy (from 43% to 29%, P < 0.001), cervical tear (3.8%
      to 1.5%, P = 0.02), and median blood loss (200 ml to 150 ml; P < 0.001) were
      reduced significantly in the same period. No significant associations were
      observed in perineal tear or birth asphyxia occurrences. KEY CONCLUSIONS AND
      IMPLICATIONS FOR PRACTICE: The study suggests that there is a beneficial effect
      of care during the second stage of labour with a package of interventions in
      reducing maternal and neonatal complications, particularly in reducing the
      frequency of episiotomy, cervical tear, and blood loss during delivery. The
      preferred choice of posture during giving birth, adopting a spontaneous pushing
      technique and continuous presence of support person during the second stage of
      labour may be encouraged for better health outcomes.

PMID- 30107288
TI  - Modulating acoustic Fano resonance of self-collimated sound beams in two
      dimensional sonic crystals.
AB  - Controlling the lineshape of Fano resonance has great potential applications.
      Here we propose a type of acoustic Fano resonator, which is composed of a multi
      layer zigzag line defects (ZLDs) sandwiched by double-layer zigzag steel rods in
      two-dimensional sonic crystals (SCs). We have theoretically and experimentally
      observed the asymmetric Fano resonances caused by the interference between the
      resonant and propagating self-collimated acoustic waves. It is demonstrated that
      the resonance dip frequency and Fano profile can be modulated by adjusting the
      structure parameters of the SC-based resonator. Our finding provides an efficient
      approach to manipulate sound propagation for future acoustic devices.

PMID- 30107289
TI  - Effects of APOE epsilon4 on neuroimaging, cerebrospinal fluid biomarkers, and
      cognition in prodromal Alzheimer's disease.
AB  - Apolipoprotein (APOE) epsilon4 is a major genetic risk factor for Alzheimer's
      disease (AD), but its importance for the clinical and biological heterogeneity in
      AD is unclear, particularly at the prodromal stage. We analyzed 151 prodromal AD
      patients (44 APOE epsilon4-negative and 107 APOE epsilon4-positive) from the
      BioFINDER study. We tested cognition, 18F-flutemetamol beta-amyloid (Abeta)
      positron emission tomography, cerebrospinal fluid biomarkers of Abeta, tau and
      neurodegeneration, and magnetic resonance imaging of white matter pathology and
      brain structure. Despite having similar cortical Abeta-load and baseline global
      cognition (mini mental state examination), APOE epsilon4-negative prodromal AD
      had more nonamnestic cognitive impairment, higher cerebrospinal fluid levels of
      Abeta-peptides and neuronal injury biomarkers, more white matter pathology, more
      cortical atrophy, and faster decline of mini mental state examination, compared
      to APOE epsilon4-positive prodromal AD. The absence of APOE epsilon4 is
      associated with an atypical phenotype of prodromal AD. This suggests that APOE
      epsilon4 may impact both the diagnostics of AD in early stages and potentially
      also effects of disease-modifying treatments.

PMID- 30107290
TI  - Chirality transitions and transport properties of individual few-walled carbon
      nanotubes as revealed by in situ TEM probing.
AB  - Physical properties of carbon nanotubes (CNTs) are closely related to the atomic
      structure, i.e. the chirality. It is highly desirable to develop a technique to
      modify their chirality and control the resultant transport properties. Herein, we
      present an in situ transmission electron microscopy (TEM) probing method to
      monitor the chirality transition and transport properties of individual few
      walled CNTs. The changes of tube structure including the chirality are stimulated
      by programmed bias pulses and associated Joule heating. The chirality change of
      each shell is analyzed by nanobeam electron diffraction. Supported by molecular
      dynamics simulations, a preferred chirality transition path is identified,
      consistent with the Stone-Wales defect formation and dislocation sliding
      mechanism. The electronic transport properties are measured along with the
      structural changes, via fabricating transistors using the individual nanotubes as
      the suspended channels. Metal-to-semiconductor transitions are observed along
      with the chirality changes as confirmed by both the electron diffraction and
      electrical measurements. Apart from providing an alternative route to control the
      chirality of CNTs, the present work demonstrates the rare possibility of
      obtaining the dynamic structure-properties relationships at the atomic and
      molecular levels.

PMID- 30107291
TI  - Influences of heatwave, rainfall, and tree cover on cholera in Bangladesh.
AB  - Cholera is a severe diarrheal disease and remains a global threat to public
      health. Climate change and variability have the potential to increase the
      distribution and magnitude of cholera outbreaks. However, the effect of heatwave
      on the occurrence of cholera at individual level is still unclear. It is also
      unknown whether the local vegetation could potentially mitigate the effects of
      extreme heat on cholera outbreaks. In this study, we designed a case-crossover
      study to examine the association between the risk of cholera and heatwaves as
      well as the modification effects of rainfall and tree cover. The study was
      conducted in Matlab, a cholera endemic area of rural Bangladesh, where cholera
      case data were collected between January 1983 and April 2009. The association
      between the risk of cholera and heatwaves was examined using conditional logistic
      regression models. The results showed that there was a higher risk of cholera two
      days after heatwaves (OR = 1.53, 95% CI: 1.07-2.19) during wet days (rainfall > 0
      mm). For households with less medium-dense tree cover, the heatwave after a 2-day
      lag was positively associated (OR = 1.80, 95% CI: 1.01-3.22) with the risk of
      cholera during wet days. However, for households with more medium-dense tree
      cover, the association between the risk of cholera and heatwave in 2-day lag was
      not significant. These findings suggest that heatwaves might promote the
      occurrence of cholera, while this relationship was modified by rainfall and tree
      cover. Further investigations are needed to explore major mechanisms underlying
      the association between heatwaves and cholera as well as the beneficial effects
      of tree cover.

PMID- 30107292
TI  - A multicity study of air pollution and cardiorespiratory emergency department
      visits: Comparing approaches for combining estimates across cities.
AB  - Determining how associations between ambient air pollution and health vary by
      specific outcome is important for developing public health interventions. We
      estimated associations between twelve ambient air pollutants of both primary
      (e.g. nitrogen oxides) and secondary (e.g. ozone and sulfate) origin and
      cardiorespiratory emergency department (ED) visits for 8 specific outcomes in
      five U.S. cities including Atlanta, GA; Birmingham, AL; Dallas, TX; Pittsburgh,
      PA; St. Louis, MO. For each city, we fitted overdispersed Poisson time-series
      models to estimate associations between each pollutant and specific outcome. To
      estimate multicity and posterior city-specific associations, we developed a
      Bayesian multicity multi-outcome (MCM) model that pools information across cities
      using data from all specific outcomes. We fitted single pollutant models as well
      as models with multipollutant components using a two-stage chemical mixtures
      approach. Posterior city-specific associations from the MCM models were somewhat
      attenuated, with smaller standard errors, compared to associations from time
      series regression models. We found positive associations of both primary and
      secondary pollutants with respiratory disease ED visits. There was some
      indication that primary pollutants, particularly nitrogen oxides, were also
      associated with cardiovascular disease ED visits. Bayesian models can help to
      synthesize findings across multiple outcomes and cities by providing posterior
      city-specific associations building on variation and similarities across the
      multiple sources of available information.

PMID- 30107293
TI  - Source-specific lung cancer risk assessment of ambient PM2.5-bound polycyclic
      aromatic hydrocarbons (PAHs) in central Tehran.
AB  - In this study, source-specific cancer risk characterization of ambient PM2.5
      bound polycyclic aromatic hydrocarbons (PAHs) was performed in central Tehran.
      The positive matrix factorization (PMF) model was applied for source
      apportionment of PAHs in the area from May 2012 through May 2013. The PMF runs
      were carried out using chemically analyzed PAHs mass concentrations. Five factors
      were identified as the major sources of airborne PAHs in central Tehran,
      including petrogenic sources and petroleum residue, natural gas and biomass
      burning, industrial emissions, diesel exhaust emissions, and gasoline exhaust
      emissions, with approximately similar contributions of around 20% to total PAHs
      concentration from each factor. Results of the PMF source apportionment (i.e.,
      PAHs factor profiles and contributions) were then used to calculate the source
      specific lung cancer risks for outdoor and lifetime exposure, using the
      benzo[alpha]pyrene (BaP) equivalent method. Our risk assessment analysis
      indicated that the lung cancer risk associated with each specific source is
      within the range of 10-6-10-5, posing cancer risks exceeding the United States
      Environmental Protection Agency's (USEPA) guideline safety values (10-6).
      Furthermore, the epidemiological lung cancer risk for lifetime exposure to total
      ambient PAHs was found to be (2.8 +/- 0.78) * 10-5. Diesel exhaust and industrial
      emissions were the two sources with major contributions to the overall cancer
      risk, contributing respectively to 39% and 27% of the total risk associated with
      exposure to ambient PAHs. Results from this study provide an estimate of the
      cancer risk caused by exposure to ambient PAHs in highly crowded areas in central
      Tehran, and can be used as a guide for the adoption of effective air quality
      policies in order to reduce the human exposure to these harmful organic species.

PMID- 30107294
TI  - Master athletes have higher miR-7, SIRT3 and SOD2 expression in skeletal muscle
      than age-matched sedentary controls.
AB  - Regular physical exercise has health benefits and can prevent some of the ageing
      associated muscle deteriorations. However, the biochemical mechanisms underlying
      this exercise benefit, especially in human tissues, are not well known. To
      investigate, we assessed this using miRNA profiling, mRNA and protein levels of
      anti-oxidant and metabolic proteins in the vastus lateralis muscle of master
      athletes aged over 65 years and age-matched controls. Master athletes had lower
      levels of miR-7, while mRNA or protein levels of SIRT3, SIRT1, SOD2, and FOXO1
      levels were significantly higher in the vastus lateralis muscle of master
      athletes compared to muscles of age-matched controls. These results suggest that
      regular exercise results in better cellular metabolism and antioxidant capacity
      via maintaining physiological state of mitochondria and efficient ATP production
      and decreasing ageing-related inflammation as indicated by the lower level of miR
      7 in master athletes.

PMID- 30107295
TI  - Hippocampal neurons require a large pool of glutathione to sustain dendrite
      integrity and cognitive function.
AB  - Loss of brain glutathione has been associated with cognitive decline and neuronal
      death during aging and neurodegenerative diseases. However, whether decreased
      glutathione precedes or follows neuronal dysfunction has not been unambiguously
      elucidated. Previous attempts to address this issue were approached by fully
      eliminating glutathione, a strategy causing abrupt lethality or premature
      neuronal death that led to multiple interpretations. To overcome this drawback,
      here we aimed to moderately decrease glutathione content by genetically knocking
      down the rate-limiting enzyme of glutathione biosynthesis in mouse neurons in
      vivo. Biochemical and morphological analyses of the brain revealed a modest
      glutathione decrease and redox stress throughout the hippocampus, although
      neuronal dendrite disruption and glial activation was confined to the hippocampal
      CA1 layer. Furthermore, the behavioral characterization exhibited signs
      consistent with cognitive impairment. These results indicate that the hippocampal
      neurons require a large pool of glutathione to sustain dendrite integrity and
      cognitive function.

PMID- 30107297
TI  - A review of UK media coverage of physical activity associated with the
      publication of special issues in a high-impact medical journal.
AB  - OBJECTIVES: The media is a substantial vehicle for conveying public health
      messages to the public. This study examined the extent to which the publication
      of special issues in a high-impact medical journal in 2012 and 2016 generated
      media interest in physical activity and health in the UK and explored the main
      issues that were reported. STUDY DESIGN: This is a systematic narrative review of
      print media. METHODS: Relevant print news articles were identified by searching
      Factiva and Google News. The timeframe of each search was 2 weeks, using the
      publication date of each special issue as the anchor point. Overall, 20 articles
      were included in the analysis for 2012 and 37 articles for 2016. RESULTS: The
      news media coverage was encouraging for the profile of physical activity and
      health. In 2012 and 2016, common themes included the benefits of physical
      activity and the risks of being inactive, comparisons between mortality rates
      from physical inactivity and smoking and the recommended volume of physical
      activity to benefit health. CONCLUSIONS: The profile given to an issue through
      prestigious scientific publication is one of the levers for community attention
      and policy change. Efforts are needed to further use the media for improving
      policy, practice and public awareness, which are antecedents to population health
      change.

PMID- 30107296
TI  - The Parkinson's disease gene product DJ-1 modulates miR-221 to promote neuronal
      survival against oxidative stress.
AB  - DJ-1 is a highly conserved protein that protects neurons against oxidative stress
      and whose loss of function mutations are linked to recessively inherited
      Parkinson's disease (PD). While a number of signaling pathways have been shown to
      be regulated by DJ-1, its role in controlling cell survival through non-coding
      RNAs remains poorly understood. Here, using a microarray screen, we found that
      knocking down DJ-1 in human neuroblastoma cells results in down-regulation of
      microRNA-221 (miR-221). This is one of the most abundant miRNAs in the human
      brain and promotes neurite outgrowth and neuronal differentiation. Yet the
      molecular mechanism linking miR-221 to genetic forms of PD has not been studied.
      Consistent with the microarray data, miR-221 expression is also decreased in DJ-1
      /- mouse brains. Re-introduction of wild-type DJ-1, but not its PD-linked
      pathogenic M26I mutant, restores miR-221 expression. Notably, over-expression of
      miR-221 is protective against 1-methyl-4-phenylpyridinium (MPP+)-induced cell
      death, while inhibition of endogenous miR-221 sensitizes cells to this toxin.
      Additionally, miR-221 down-regulates the expression of several pro-apoptotic
      proteins at basal conditions and prevents oxidative stress-induced up-regulation
      of bcl-2-like protein 11 (BIM). Accordingly, miR-221 protects differentiated DJ-1
      knock-down ReNcell VM human dopaminergic neuronal cells from MPP+-induced neurite
      retraction and cell death. DJ-1 is a known activator of the mitogen-activated
      protein kinase (MAPK)/extracellular-regulated kinase (ERK) pathway and may
      modulate miR-221 levels in part through this pathway. We found that inhibiting
      ERK1/2 decreases miR-221 levels, whereas over-expressing ERK1 in DJ-1 knock-down
      cells increases miR-221 levels. These findings point to a new cytoprotective
      mechanism by which DJ-1 may increase miR-221 expression through the MAPK/ERK
      pathway, subsequently leading to repression of apoptotic molecules. The inability
      of a pathogenic DJ-1 mutant to modulate miR-221 further supports the relevance of
      this mechanism in neuronal health and its failure in DJ-1-linked PD.

PMID- 30107299
TI  - Adversarial relationship between combined medial olivocochlear (MOC) and middle
      ear-muscle (MEM) reflexes and alarm-in-noise detection thresholds under negative
      signal-to-noise ratios (SNRs).
AB  - The role of auditory efferent feedback from the medial olivocochlear system
      (MOCS) and the middle-ear-muscle (MEM) reflex in tonal detection tasks for humans
      in the presence of noise is not clearly understood. Past studies have yielded
      inconsistent results on the relationship between efferent feedback and tonal
      detection thresholds. This study attempts to address this inconsistency. Fifteen
      human subjects with normal hearing participated in an experiment where they were
      asked to identify an alarm signal in the presence of 80 dBA background (pink)
      noise. Masked detection thresholds were estimated using the method of two
      interval forced choice (2IFC). Contralateral suppression of transient-evoked
      otoacoustic emissions (TEOAEs) was measured to estimate the strength of auditory
      efferent feedback. Subsequent correlation analysis revealed that the
      contralateral suppression of TEOAEs was significantly negatively correlated (r = 
      0.526, n = 15, p = 0.0438) with alarm-in-noise (AIN) detection thresholds under
      negative signal-to-noise conditions. The result implies that the stronger the
      auditory efferent feedback, the worse the detection thresholds and thus the
      poorer the tonal detection performance in the presence of loud noise.

PMID- 30107298
TI  - Resistance of high fitness hepatitis C virus to lethal mutagenesis.
AB  - Viral fitness quantifies the degree of virus adaptation to a given environment.
      How viral fitness can influence the mutant spectrum complexity of a viral
      quasispecies subjected to lethal mutagenesis has not been investigated. Here we
      document that two high fitness hepatitis C virus populations display higher
      resistance to the mutagenic nucleoside analogues favipiravir and ribavirin than
      their parental, low fitness HCV. All populations, however, exhibited a mutation
      transition bias indicative of active mutagenesis. Resistance to the analogues was
      associated with a limited expansion of mutant spectrum complexity, as evidenced
      by several diversity indices used to characterize mutant spectra. The results are
      consistent with a replicative site-drug competition mechanism that was previously
      proposed for HCV fitness-associated resistance to non-mutagenic inhibitors. Other
      alternative, non-mutually exclusive mechanisms are considered. The results
      introduce viral fitness as a relevant parameter to evaluate the response of
      viruses to lethal mutagenesis, with implications for antiviral designs.

PMID- 30107300
TI  - In vitro effect of Porphyromonas gingivalis combined with influenza A virus on
      respiratory epithelial cells.
AB  - OBJECTIVE: Respiratory epithelial cells are the first natural barrier against
      bacteria and viruses; hence, the interactions among epithelial cells, bacteria,
      and viruses are associated with disease occurrence and development. The effect of
      co-infection by P. gingivalis and influenza A virus (IAV) on respiratory
      epithelial cells remains unknown. The aim of this study was to analyze in vitro
      cell viability and apoptosis rates in respiratory epithelial A549 cells infected
      with P. gingivalis or IAV alone, or a combination of both pathogens. DESIGN: A549
      cells were first divided into a control group, a P. gingivalis group, an IAV
      group, and a P. gingivalis + IAV group, to examine cell viability and apoptosis
      rates, the levels of microtubule associated protein 1 light chain 3 B (LC3-II),
      microtubule associated protein 1 light chain 3A (LC3-I), and sequestosome 1
      (P62), and the formation of autophagosomes. The autophagy inhibitor, 3
      methyladenine (3MA), was used to assess autophagy and apoptosis in A549 cells
      infected with P. gingivalis or IAV. RESULTS: An MTT assay revealed that cell
      viability was significantly lower in the IAV group than in the P. gingivalis +
      IAV group (P < 0.05). Flow cytometry indicated that the apoptosis rate was
      significantly higher in the IAV group than in the P. gingivalis + IAV group (P <
      0.05). The fluorescence levels of GFP-LC3 increased significantly, the LC3-II/LC3
      I ratio was significantly higher, and the P62 protein levels were statistically
      lower in the P. gingivalis + IAV group compared with the IAV group (all P <
      0.05). Western blotting revealed that the LC3- II/LC3-I ratio was significantly
      lower, and caspase-3 levels were significantly higher in the 3MA + P. gingivalis
      + IAV group compared to the P. gingivalis + IAV group (all P < 0.05). CONCLUSION:
      In vitro studies showed that infection by P. gingivalis combined with IAV
      temporarily inhibited apoptosis in respiratory epithelial cells, and this may be
      related to the initiation of autophagy.

PMID- 30107301
TI  - Root and root canal variations of the human maxillary and mandibular third molars
      in a Chinese population: A micro-computed tomographic study.
AB  - OBJECTIVES: To investigate the anatomical variations of the root and root canal
      configuration of the human third molars. DESIGNS: A total of 130 maxillary and
      130 mandibular third molars were collected from a native Chinese population. All
      teeth were scanned by micro-computed tomography. After 3D reconstruction, the
      root and canal morphology of each tooth was examined both qualitatively and
      quantitatively. RESULTS: For maxillary molars, a single fused root (67 cases,
      51.5%) and a single root canal system (64 cases, 49.2%) was most common
      root/canal form; the typical three-rooted molars were detected only in 33 cases
      (25.4%), and the secondary MB canals were detected only in 9 molars (6.9%). For
      mandibular molars, 62 teeth were single-rooted (47.7%) and 42 had a single root
      canal system (32.3%); 20 singled-rooted and 60 double-rooted molars exhibited
      independent mesial and distal root canal systems (61.5%), and the type 1-1 canal
      was the most common configuration for mesial (57 cases) and distal (81 cases)
      root canal systems. C-shaped canals were detected in 11 maxillary and 36
      mandibular single-rooted molars. The mean root surface area, root and crown
      volume of mandibular third molars were significantly higher than the maxillary
      third molars (P <  0.01). CONCLUSION: The root canal system of the third molars
      may exhibit several anatomic variations. Whereas in most of cases, the degree of
      the canal differentiation was at a low level, and the canal form was not
      complicate.

PMID- 30107302
TI  - Reducing water use by alternate-furrow irrigation with livestock wastewater
      reduces antibiotic resistance gene abundance in the rhizosphere but not in the
      non-rhizosphere.
AB  - Livestock wastewater is rich in nutrients but may contain antibiotics and
      antibiotic resistance genes (ARGs). Their discharge to watercourses or soil may
      result in proliferation of ARGs. Irrigation with wastewater appears to be the
      most feasible option of disposing of it. One efficient irrigation technology used
      in arid regions is alternate-furrow irrigation (AFI) by alternately drying part
      of the plant roots for a prolonged period to physiologically reduce transpiration
      without compromising yield. However, the extent to which AFI with wastewater
      influences the concentration of antibiotics and spread of ARGs in soil is poorly
      understood. The purpose of this paper is to investigate how AFI using swine
      wastewater alters antibiotic kinetics and ARGs abundance under different
      irrigation rates, using pepper as the model plant. We examined three AFI
      treatments using 50%, 65% and 80% of the amount of water employed in sufficient
      conventional furrow irrigation. Each treatment had a groundwater irrigation
      control. The results showed that antibiotic concentrations and relative ARGs
      abundance in the top 20 cm of soil did not increase with the irrigation amount,
      although they were higher than those in the groundwater-irrigated soils. The
      relative ARGs abundance in the soil was modulated by irrigation amount and
      reducing the irrigation amount in AFI reduced ARGs dispersion only in
      rhizosphere. When the soil moisture was close to field capacity, ARGs were more
      abundant in rhizosphere than in non-rhizosphere, possibly because the rhizosphere
      is rich in microbes and increasing antibiotic concentrations due to an increase
      in irrigation rate favors antibiotic-resistant microbiome in competing for
      substrates. These, however, were not mirrored in the relative ARGs abundance in
      the roots. These results have important implications as it revealed that reducing
      the input of antibiotics and ARGs into soil with AFI does not necessarily reduce
      ARGs proliferation.

PMID- 30107303
TI  - Scoping studies to establish the capability and utility of a real-time bioaerosol
      sensor to characterise emissions from environmental sources.
AB  - A novel dual excitation wavelength based bioaerosol sensor with multiple
      fluorescence bands called Spectral Intensity Bioaerosol Sensor (SIBS) has been
      assessed across five contrasting outdoor environments. The mean concentrations of
      total and fluorescent particles across the sites were highly variable being the
      highest at the agricultural farm (2.6 cm-3 and 0.48 cm-3, respectively) and the
      composting site (2.32 cm-3 and 0.46 cm-3, respectively) and the lowest at the
      dairy farm (1.03 cm-3 and 0.24 cm-3, respectively) and the sewage treatment works
      (1.03 cm-3 and 0.25 cm-3, respectively). In contrast, the number-weighted
      fluorescent fraction was lowest at the agricultural site (0.18) in comparison to
      the other sites indicating high variability in nature and magnitude of emissions
      from environmental sources. The fluorescence emissions data demonstrated that the
      spectra at different sites were multimodal with intensity differences largely at
      wavelengths located in secondary emission peaks for lambdaex 280 and lambdaex
      370. This finding suggests differences in the molecular composition of emissions
      at these sites which can help to identify distinct fluorescence signature of
      different environmental sources. Overall this study demonstrated that SIBS
      provides additional spectral information compared to existing instruments and
      capability to resolve spectrally integrated signals from relevant biological
      fluorophores could improve selectivity and thus enhance discrimination and
      classification strategies for real-time characterisation of bioaerosols from
      environmental sources. However, detailed lab-based measurements in conjunction
      with real-world studies and improved numerical methods are required to optimise
      and validate these highly resolved spectral signatures with respect to the
      diverse atmospherically relevant biological fluorophores.

PMID- 30107304
TI  - An overview of patterns and dynamics of suspended sediment transport in an
      agroforest headwater system in humid climate: Results from a long-term
      monitoring.
AB  - Small headwater catchments deliver large quantities of suspended sediment (SS) to
      the ocean. However, there are relatively few studies focused on the study of
      patterns and dynamics of suspended sediment in headwater catchments over the long
      term (10 year or more). In this study, the dynamics of suspended sediment
      transport were examined at different time scales in a small headwater catchment
      in NW Spain, based on a 12-year dataset from high-resolution monitoring. The
      results revealed that, similar to other humid catchments, the hydrological
      response was highly dependent on initial conditions, especially in autumn and
      summer. However, in winter and spring the hydrology was more influenced by
      rainfall amount. The annual suspended sediment was 117 Mg, which equates to a
      suspended sediment yield of 10 Mg km-2 y-1. The SS yield in the Corbeira
      catchment is related to runoff generation and flooding, which play a key role in
      sediment yield from the catchment. About 80% of the annual SS was transported
      over 12% of the study period. Rainfall and discharge at the beginning of the
      events were the most important factors in explaining the hydrological response at
      event scale. Suspended sediment transport in this catchment is determined by
      event magnitude, while the SS is mainly influenced by variables related to runoff
      erosivity.

PMID- 30107305
TI  - Finding order in a bustling construction zone: quantitative imaging and analysis
      of cell wall assembly in plants.
AB  - Assembly of polysaccharide-based walls by plant cells involves the rapid
      synthesis, trafficking, and deposition of complex biopolymers, but how these
      events are controlled and coordinated to achieve a strong, resilient
      extracellular matrix has remained obscure for decades. Recent quantitative
      analyses of fluorescence microscopy data have revealed details of the trafficking
      and synthetic activity of cellulose synthases, and new methods for labeling
      matrix polymers have unveiled aspects of their regulated deposition in the wall.
      Detailed studies of the identity, architecture, activity, and trafficking of the
      proteins and protein complexes that synthesize wall polymers, combined with
      advances in image acquisition and analysis, will aid future efforts to dissect
      wall assembly.

PMID- 30107306
TI  - Mental health consumer concept mapping of supportive community.
AB  - This research engaged consumers with severe and persistent mental illness
      receiving services in the public mental health sector in creating a comprehensive
      list of 110 needed community services and supports, then individually sorting and
      rating these items. Within the resulting concept map generated by Concept System
      software and as interpreted by the study participants, successfully living in the
      community is actualized when there is an outer layer of support regarding basic
      needs; financial means; individualized, comprehensive and available services;
      competent and caring staff; community education; legal rights enforcement; and
      social change directed at dismantling the discrimination and stigma associated
      with mental illness. Peer support and services is critical component, providing a
      transformational space from basic survival into recovery, supporting personal
      development and skills building and further social development. This study
      demonstrates that adult public mental health consumers actively receiving
      services can engage in collaborative research in meaningfully determining what
      their needs are, conceptualizing what the services should be and how developed,
      and articulating service prioritization.

PMID- 30107307
TI  - Copper(II) complexation by fragment of central part of FBP28 protein from Mus
      musculus.
AB  - Steady-state and time-resolved fluorescence spectroscopy, UV spectrophotometry
      and isothermal titration calorimetry techniques were used to study the
      coordinating properties of the 17aa peptide fragment (D17) derived from the
      central part of the mouse formin binding protein (FBP28 with the PDB code: 1E0L)
      towards Cu2+ ions. All the measurements were run in the 2-(N
      morpholino)ethanesulfonic acid buffer (20 mM, pH 6.0). Under experimental
      conditions the formation of the 1:1 complex of Cu2+ ions with D17 is an entropy
      driven process. Cu2+ ions cause the static fluorescence quenching of the peptide
      studied through the formation of a non-fluorescent complex. Furthermore, the
      thermal stability of D17 was discussed based on the results obtained from
      differential scanning fluorimetry (nanoDSF) data.

PMID- 30107308
TI  - Critical sectors and paths for climate change mitigation within supply chain
      networks.
AB  - Certain sectors and paths along supply chains play a critical role in climate
      change mitigation. We develope a consumption-based framework, which combines
      input-output analysis, a power-of-pull approach and structural path analysis, and
      applied it to supply chain networks derived from 2010 and 2012 Jing-Jin-Ji
      interregional input-output tables. The aim of this study is to identify (1) the
      key economic sectors for controlling carbon emissions and their changes, (2) the
      critical directions from a carbon-pulling sector to the emissions of key economic
      sectors, and (3) the paths with the largest carbon emissions flux in these
      critical directions. Our results show that the key sectors are from Hebei and
      Tianjin, more concentrated in Hebei. Most sectors have the largest pulling power
      over their own carbon emissions, and within-region connections dominated in the
      emission network, with a stronger tie between Beijing and the other two regions.
      Critical paths along carbon-pulling directions are located in tiers 0 and 1. Our
      framework can provide new insight into the creation of carbon emissions control
      policies.

PMID- 30107309
TI  - Exploratory study on modification of sludge-based activated carbon for nutrient
      removal from stormwater runoff.
AB  - Nutrients (P, N) in stormwater runoff are a major cause of eutrophication and
      algal blooms. A promising solution to this problem is to amend the rain garden
      growing medium (RGGM) with sewage sludge-based activated carbon (SBAC). To
      optimize the SBAC production process, different metals, pyrolysis conditions
      (temperature, heating time, carrier gas), and post-treatments were explored. When
      pyrolyzed at 400  degrees C for two hours, Zn-activated SBAC removed up to 41% of
      PO4-P (initial concentration of 1 mg/L) and 72% of NO3-N (initial concentration
      of 2 mg/L), at a dose of 1 g sorbent/L of nutrient-spiked distilled water. When
      the same dosage was applied to stormwater leachate made from RGGM and spiked with
      nutrients, the removal efficiencies were reduced to 20% for PO4-P and 38% for NO3
      N. These reductions were probably caused by competition from other leachate
      components. Increasing the dosage to 3 g/L leachate improved PO4-P removal to 31%
      and NO3-N to 72%, while also resulting in the removal of 46% of total organic
      carbon. The major energy cost of producing such sorbents is estimated to be
      ~$0.76 CAD/kg SBAC.

PMID- 30107311
TI  - The possible mediating effect of alcohol dependence on the relationship between
      adverse childhood experiences and attempted suicide.
AB  - Adverse childhood experiences (ACEs) and alcohol dependence (AD) carry
      independent risks for suicidal behavior. While the strength of the association
      between ACEs and attempted suicide is weakened following adjustment for AD, no
      study to date has directly been performed to determine whether AD affects the
      risk of suicide attributable to ACEs. The study aimed to examine the possible
      role of alcohol dependence (AD) in the relationship between various ACEs and
      attempted suicide. This cross-sectional study assessed history of ACEs among 184
      AD patients and 205 control participants using the Family Health Questionnaire.
      Lifetime history of attempted suicide was collected using the Chinese version of
      the Composite International Diagnostic Interview. We used the Sobel test to
      examine the mediating effects of AD on the relationship between ACEs and
      attempted suicide. Results showed that the suicide attempters were associated
      with higher rates of AD and ACEs. The regression analysis showed that AD and
      multiple ACEs exposure are independently associated with attempted suicide. AD
      appears as a partial mediator in the relationship between attempted suicide and
      the specific type of ACE (exposure to a battered mother or sexual abuse) or
      exposure to >=3 types of ACEs. We conclude that AD might partially mediate the
      associations detected between attempted suicide and exposure to a battered
      mother, sexual abuse, and >=3 types of ACEs. These observations may provide
      important insight for intervention strategies aimed at reducing the risk of
      suicide attempts.

PMID- 30107310
TI  - Multi-criteria decision-making for sustainable metropolitan cities assessment.
AB  - The recent development of metropolitan cities, especially in Europe, requires an
      effective integrated management of city services, infrastructure, and
      communication networks at a metropolitan level. A preliminary step towards a
      proper organizational and management strategy of the metropolitan city is the
      analysis, benchmarking and optimization of the metropolitan areas through a set
      of indicators coherent with the overall sustainability objective of the
      metropolitan city. This paper proposes the use of the Analytic Hierarchy Process
      multi-criteria decision making technique for application in the smart
      metropolitan city context, with the aim of analysing the sustainable development
      of energy, water and environmental systems, through a set of objective
      performance indicators. Specifically, the 35 indicators defined for the
      Sustainable Development of Energy, Water and Environment Systems Index framework
      are used. The application of the approach to the real case study of four
      metropolitan areas (Bari, Bitonto, Mola, and Molfetta) in the city of Bari
      (Italy) shows its usefulness for the local government in benchmarking
      metropolitan areas and providing decision indications on how to formulate the
      sustainable development strategy of the metropolitan city. Based on the Analytic
      Hierarchy Process characteristics, the results highlight that although one
      specific area (Mola in the considered case) is globally ranked at the first
      place, it is only ranked first with respect to some dimensions. Such a result has
      strong implications for the metropolitan city's manager who has the possibility
      to identify and implement targeted actions, which may be designed ad hoc to
      improve specific dimensions based on the current state of the city, thus
      maximizing the efficiency and effectiveness of the actions undertaken for the
      sustainable development of energy, water and environmental systems of the whole
      metropolitan city.

PMID- 30107312
TI  - Predictors of mental health literacy in older people.
AB  - OBJECTIVES: Older adults exhibit poorer mental health literacy than younger
      adults, including less accuracy at identifying symptoms of mental disorders, and
      endorsing fewer sources of treatment for a mental disorder. The current study's
      intention was to determine if the executive component of cognition is associated
      with mental health literacy in older adults, when controlling for other
      established predictors (sex, age, education, and proximity to someone with a
      mental disorder). METHOD: The sample included 85 cognitively healthy adults aged
      60 and over. Participants completed the Mini-Addenbrooke's Cognitive Examination
      III, the Trail Making Test, a Phonemic Verbal Fluency Test, and the Mental Health
      Literacy Scale. RESULTS: A multiple regression indicated that age and mental
      health proximity significantly and uniquely predicted total mental health
      literacy (Age: beta = -0.22, t = -2.04, p < 0.05; Proximity: beta = 0.31, t =
      2.78, p < 0.01). Older age predicted poorer PTSD mental health literacy (beta = 
      0.31, t = -2.90, p < 0.01). CONCLUSION: In neurologically healthy older adults,
      level of executive function did not contribute to mental health literacy. Older
      adults in closer proximity to someone with a mental disorder were more likely to
      have better mental health literacy, a finding that has the potential to inform
      mental health education and promotion strategies in this population.

PMID- 30107313
TI  - Prevalence of hepatitis C virus in young people who inject drugs in four
      Colombian cities: A cross-sectional study using Respondent Driven Sampling.
AB  - BACKGROUND: Colombia has a growing population of young people who inject drugs
      (PWID). Despite the previously reported association of injection drug use with
      hepatitis c virus (HCV) in other countries, studies on HCV prevalence in PWID in
      Colombia are lacking. The objective of this study is to determine the prevalence,
      demographics, and correlations of risky injection behaviours in HCV seropositive
      PWID in four Colombian cities (Armenia, Bogota, Cucuta and Pereira). METHODS:
      This was a cross-sectional study carried out between January and June of 2014
      that included 918 PWID from four Colombian cities, recruited by Respondent Driven
      Sampling. A survey was administered to each participant, and blood samples were
      collected. Binary logistic regression and multivariate analyses for each city
      were conducted. RESULTS: Average participant age was 26 years (SD 6.5). Of all
      participants, 27.3% of PWID were HCV seropositive, of which 52% were 25 years old
      or younger. In Pereira, increased risk of HCV infection was found for PWID that:
      had a history of injection drug use of 5 years or more (AOR: 3.0, CI: 1.7-7.8);
      were between 25 and 28 years of age (AOR: 5.2, CI: 1.0-26.3); had higher
      injection frequency (AOR: 2.5, CI: 1.4-4.2), and daily use of gifted, sold, or
      rented needles or syringes (AOR: 4.5, CI: 1.0-7.1). Additionally, in Cucuta,
      being HIV seropositive appeared to be greatly associated with risk of HCV
      seropositivity (AOR: 16.9, CI: 3.5-81.5). CONCLUSION: Although prevalence of HCV
      in PWID in Colombia is lower than that reported for other countries, the
      described demographic characteristics and diverse risky injection behaviors on
      each city, in the context of a young PWID population with a short injection drug
      use history, should be taken into account in order to guide efforts towards
      preventing and reducing risk of HCV infection in PWID in Colombia.

PMID- 30107314
TI  - Socio-cultural and neurobiological perspectives of betel nut chewing in
      schizophrenia.

PMID- 30107315
TI  - Age at onset of first suicide attempt: Exploring the utility of a potential
      candidate variable to subgroup attempters.
AB  - PURPOSE: Our objective was to explore the utility of age at first suicide attempt
      in identifying subgroups of suicide attempters. METHODS: In a retrospective study
      design, we collected information from the clinical charts of 895 patients
      assessed over a seven-year period. Admixture analysis was used to determine the
      best fitting theoretical model for distribution of age at first attempt that
      divided the sample. Subsequently, multivariate analysis was performed to identify
      variables that distinguished the subgroups identified. RESULTS: The theoretical
      solution that best explained the observed distribution of age at first suicide
      attempt was a mixture of two Gaussian distributions with a cut-off of 31 years
      for the two subgroups. In logistic regression analysis, male gender (Odds ratios
      [OR] 3.047, 95% Confidence Interval (CI) 1.818-5.106), fewer years of formal
      schooling (OR 3.384, 95% CI 1.701-6.734) and being married (OR 23.36, 95% CI
      10.753-50.000), were more commonly associated with the late onset subgroup (age
      at first attempt >31 years). Further, the late onset subgroup had poorer global
      functioning (OR 0.980, 95% CI 0.962 to 0.998). CONCLUSION: Age at onset of first
      suicide attempt is a useful candidate marker to delineate an early and late onset
      subgroup among suicide attempters. These results are likely to inform
      customization of suicide prevention strategies.

PMID- 30107317
TI  - Attachment and leadership: review and new insights.
AB  - Attachment theory has inspired a new view on the topic of leadership, enabling a
      better understanding of leader-follower relations by acknowledging how attachment
      dynamics and the evolutionary foundations of human relationships apply in
      organizational contexts. Early research mainly focused on individual differences
      and demonstrated the association between attachment orientations (security,
      anxiety, and avoidance) the emergence of leaders and their behaviors (i.e.,
      leadership style). More recent research has focused on the attachment
      orientations of both leaders and followers, the role of moderating and mediating
      variables, and the provision of secure-base support and caring orientations of
      leaders. However, recent research on 'followership' highlights the centrality of
      leader competence and followers' capacity to identify, and willingness to follow,
      leaders who demonstrate this quality. We analyze the significance of competence
      in the context of attachment and leadership and suggest a new Care and Competence
      Model based on evolutionary claims.

PMID- 30107316
TI  - Effects of nanosilver on Mytilus galloprovincialis hemocytes and early embryo
      development.
AB  - Silver nanoparticles (AgNP), one of the main nanomaterials for production and
      use, are expected to reach the aquatic environment, representing a potential
      threat to aquatic organisms. In this study, the effects of bare AgNPs (47 nm) on
      the marine mussel Mytilus galloprovincialis were evaluated at the cellular and
      whole organism level utilizing both immune cells (hemocytes) and developing
      embryos. The effects were compared with those of ionic Ag+(AgNO3). In vitro short
      term exposure (30 min) of hemocytes to AgNPs induced small lysosomal membrane
      destabilization (LMS EC50 = 273.1 MUg/mL) and did not affect other immune
      parameters (phagocytosis and ROS production). Responses were little affected by
      hemolymph serum (HS) as exposure medium in comparison to ASW. However, AgNPs
      significantly affected mitochondrial membrane potential and actin cytoskeleton at
      lower concentrations. AgNO3 showed much higher toxicity, with an EC50 = 1.23
      MUg/mL for LMS, decreased phagocytosis and induced mitochondrial and cytoskeletal
      damage at similar concentrations. Both AgNPs and AgNO3 significantly affected
      Mytilus embryo development, with EC50 = 23.7 and 1 MUg/L, respectively. AgNPs
      caused malformations and developmental delay, but no mortality, whereas AgNO3
      mainly induced shell malformations followed by developmental arrest or death.
      Overall, the results indicate little toxicity of AgNPs compared with AgNO3;
      moreover, the mechanisms of action of AgNP appeared to be distinct from those of
      Ag+. The results indicate little contribution of released Ag+ in our experimental
      conditions. These data provide a further insight into potential impact of AgNPs
      in marine invertebrates.

PMID- 30107318
TI  - Melatonin and cortisol in individuals with spinal cord injury.
AB  - STUDY OBJECTIVES: The aim of this study was to investigate circadian rhythm and
      sleep complaints in individuals with spinal cord injury (SCI) as determined by
      diurnal saliva melatonin and cortisol as well as activity measurements and
      subjective sleep quality. METHODS: Fourteen patients with cervical SCI (cSCI),
      six patients with thoracic SCI (tSCI) and eight able-bodied controls all
      underwent two consecutive weeks wearing a wrist actigraph in addition to filling
      out a sleep diary. During one 24-h period, cortisol and melatonin were measured
      at 4-h intervals. Furthermore, participants' sleep quality was assessed using the
      Pittsburgh Sleep Quality Index (PSQI) and their overall daytime sleepiness was
      assessed using the Epworth Sleepiness Scale (ESS). RESULTS: The cSCI group
      demonstrated lower melatonin levels compared with the tSCI group and the controls
      at the 24:00 and 04:00 time points. Moreover, at one time point the tSCI group
      had a higher cortisol level than the cSCI group and the controls. In addition,
      baseline systolic blood pressure and oxygen saturation were significantly lower
      in the cSCI group. No differences were found in activity measurements or self
      reported sleep quality. CONCLUSIONS: Individuals with cSCI demonstrate reduced
      melatonin secretion compared with tSCI individuals, but not in other circadian
      measures. This supports an involvement of melatonergic cervical fibers associated
      with the cervical lesion.

PMID- 30107319
TI  - Potential adverse effects of antimicrobial chemotherapy based on ultraviolet-A
      irradiation of polyphenols against the oral mucosa in hamsters and wounded skin
      in rats.
AB  - Antimicrobial chemotherapy based on ultraviolet-A (UVA) irradiation of polyphenol
      solution has been proposed as an adjunctive treatment for dental caries. However,
      the safety of this treatment has not been thoroughly evaluated. Therefore, the
      aim of the present study was to assess the influence of this treatment on the
      oral mucosa in hamsters and wounded skin in rats. An oral mucosal irritation test
      was performed in hamsters. The cheek pouch was everted and treated with UVA
      irradiation (wavelength: 365 nm) of pure water, 1 mg/mL of caffeic acid, or 1
      mg/mL of grape seed extract using a light-emitting diode at an irradiance of 275
      mW/cm2. Each treatment was performed for 2 or 5 min and repeated three times.
      Macroscopic and histological evaluations were performed 24 h after the last
      treatment. We also examined the effects of the treatment on the healing process
      of skin wounds in rats. Full-thickness skin wounds created on the back of the
      rats were treated for 2 min as described above, but only once. The wound area was
      then assessed daily for 9 days. The results demonstrated that the treatment
      induced oral mucosal irritation depending on the irradiation time; however, it
      did not influence the wound healing process. The oral mucosal irritation
      potential of three treatment sessions performed for 2 and 5 min was minimal and
      mild to moderate, respectively, according to histological analysis. These
      findings suggest that the duration of treatment based on UVA irradiation of
      polyphenols in the oral cavity should be as short as possible, considering the
      clinical efficacy of the antimicrobial effects and the irritation potential.

PMID- 30107320
TI  - Predictors of transitions across stages of heroin use and dependence prior to
      treatment-seeking among people in treatment for opioid dependence.
AB  - BACKGROUND AND AIMS: Little is known about transition pathways among heroin users
      prior to treatment. This study examined the demographic and clinical predictors
      of transition speed from heroin use, to dependence, to first treatment episode.
      METHODS: 1149 heroin-dependent participants recruited from opioid agonist
      treatment clinics in Sydney, Australia, underwent a structured interview. Age of
      onset (AOO) was collected for heroin use, dependence and treatment-seeking,
      childhood maltreatment, psychiatric history and other substance dependence.
      Discrete-time survival analyses modelled years from onset of use to dependence,
      and from dependence to treatment-seeking, including demographic and clinical
      covariates. FINDINGS: Median AOO for first heroin use, dependence and treatment
      seeking was 18 years (inter-quartile range, or IQR = 6), 21 years (IQR = 7), and
      24 years (IQR = 10) respectively. In adjusted models, younger birth cohorts (vs.
      born <1960), greater childhood maltreatment and later AAO of first heroin use
      were associated with more rapid transitions from heroin use to dependence. Living
      independently, parental violence, and alcohol dependence were associated with
      slower transitions. Earlier treatment-seeking was associated with younger birth
      cohorts, having dependent children and later AOO of dependence. Delayed treatment
      seeking was associated with <10 years school education, living independently,
      depression and alcohol dependence. CONCLUSIONS: In this treatment sample, onset
      of heroin use occurred during late adolescence, suggesting the need for targeted
      interventions in mid-adolescence. Transitions to heroin dependence, then
      treatment-seeking, occurred during early adulthood. Rapid transitions from use to
      dependence were associated with younger birth cohorts, greater exposure to
      childhood maltreatment, and later onset of use.

PMID- 30107321
TI  - The association between lifetime polytobacco use and intention to quit among HIV
      positive cigarette smokers.
AB  - BACKGROUND: This secondary analysis aims to describe, over time, the relationship
      between HIV disease progression and intention to quit cigarette smoking among
      current monocigarette users with and without a lifetime history of polytobacco
      use. METHODS: Participants completed a baseline assessment at the time of HIV
      care initiation and four follow-up assessments (3, 6, 9, and 12-months).
      Assessments included biochemically verified smoking status and audio computer
      assisted self-interviews assessing psychosocial, substance use, and clinical
      variables known to influence smoking behaviors. Using linear and generalized
      linear fixed-effects models, we modeled the covariance structure for the repeated
      outcome measures (intention to quit and 7-day point prevalence smoking
      abstinence) across the study time points and included a three-way interaction
      term to examine the effects of disease stage and tobacco product use. RESULTS:
      Participants (N = 357) were 73.1% male, 67.3% black/African American, and had a
      mean (SD) age of 38.7 (10.6) years. At baseline, lifetime polytobacco users
      reported significantly worse HIV-related symptoms and burdens, illness
      perception, social support, and nicotine dependence. Intention to quit, but not
      smoking abstinence, was predicted by a three-way interaction between time from
      HIV care initiation, disease progression, and tobacco product use (p = .04).
      Overall, progressive HIV was associated with greater intention to quit smoking
      cigarettes. However, the relationship differed over time between the two tobacco
      product groups. CONCLUSION: Future studies should consider tailoring the timing
      of cessation interventions upon disease stage and lifetime history of polytobacco
      use.

PMID- 30107322
TI  - Subchronic toxicity and hepatocyte apoptosis of dietary olaquindox in common carp
      (Cyprinus carpio).
AB  - Olaquindox as one of the effective antimicrobial agents and growth-promoting feed
      additives, had been widely used in animal and fish production. However, few
      studies have been done to unveil its possible toxic effect and tissue injury on
      aquatic animal. In this study, the toxic effect and underlying mechanisms of
      olaquindox toxicity were investigated in common carp when feed with different
      doses of olaquindox for 90 days. The morbidity and mortality, pathological
      changes, hematology parameters, residue concentration in the tissues of common
      carp were assessed, hepatocyte apoptosis was detected through ultrastructural
      observation and flow cytometry methods. The results showed that the morbidity and
      mortality increased with the increasing dosages of dietary olaquindox, subchronic
      exposure to olaquindox caused remarkably pathological changes, including
      congestion and bleeding, intramuscular edema, vacuolar degeneration, degeneration
      and deformation in renal tubules architecture, respiratory epithelium fusion and
      intestinal epithelial microvilli disintegration. Besides, dietary olaquindox led
      to significant changes in blood biochemical parameters including red blood cell,
      hemoglobin, alanine aminotransferase and aspartate aminotransferase, an elevated
      residue concentration of olaquindox was detected in liver and kidney after
      exposure, hepatocyte apoptosis and necrosis were observed. Moreover, insulin-like
      growth factor I (IGF-I) mRNA level in liver was higher than normal level with the
      dose below 25 mg/kg olaquindox and was lower than normal level with the dose
      above 50 mg/kg. Our results demonstrated that dietary olaquindox may pose
      subchronic toxicity and residue in fish organs and provided scientific data for
      the safe application of olaquindox in fish.

PMID- 30107323
TI  - FcgammaRIIB receptor-mediated apoptosis in macrophages through interplay of
      cadmium sulfide nanomaterials and protein corona.
AB  - Humans are likely exposed to cadmium sulfide nanomaterials (CdS NMs) due to the
      increasing environmental release and in vivo application of these materials,
      which tend to accumulate and cause toxic effects in human lungs, particularly by
      interrupting the physiological functions of macrophage cells. Here, we showed
      that protein corona played an essential role in determining cellular uptake and
      cytotoxicity of CdS NMs in macrophages. Protein-coated CdS NMs enhanced the
      expression of FcgammaRIIB receptors on the cell surface, and the interaction
      between this receptors and proteins inhibited cellular uptake of CdS NMs while
      triggering cell apoptosis via the AKT/Caspase 3 signaling pathway. Cytotoxicity
      of CdS NMs was greatly alleviated by coating the nanomaterials with polyethylene
      glycol (PEG), because PEG decreased the adsorption of proteins that interact with
      the FcgammaRIIB receptors on cell surface. Overall, our research demonstrated
      that surface modification, particularly protein association, significantly
      affected cellular response to CdS NMs, and cellular uptake may not be an
      appropriate parameter for predicting the toxic effects of these nanomaterials in
      human lungs.

PMID- 30107324
TI  - Biochemical and histological alterations in adult zebrafish(Danio rerio)ovary
      following exposure to the tetronic acid insecticide spirotetramat.
AB  - As a new tetronic acid derivative insecticide, spirotetramat has been reported to
      be toxic to an array of aquatic organisms. However, the toxic effects of
      spirotetramat on zebrafish especially at ovary are still obscure. Hereby, the
      acute toxicity of spirotetramat towards zebrafish(Danio rerio),as well as the
      changes on biochemical and histological traits of ovary were investigated. The
      acute toxicity test results showed that the median lethal concentration (LC50)
      value of spirotetramat were 9.61 mg/L and 7.21 mg/L at 72 h and 96 h,
      respectively, suggesting spirotetramat has moderate toxicity to zebrafish. In the
      following sub-lethal toxicity test, the gene expression of superoxide dismutase
      (SOD), catalase (CAT), and gonadotropic hormone receptor (FSHR and LHR) together
      with the content of malondialdehyde (MDA) in ovary were measured at 14, 21, and
      28 days after exposure to 36, 360 and 720 MUg/L. Under high concentration
      treatment (360 and 720 MUg/L), MDA content, the relative transcription CAT and
      SOD gene level increased significantly in ovary (p < 0.05). That indicated sub
      lethal doses spirotetramat caused oxidative stress and lipid peroxidation in
      zebrafish ovary during the entire experimental period. Under the exposure to
      spirotetramat at 720 MUg/L after 14 days, the relative transcript FSHR gene level
      was down regulated, and the relative transcript LHR gene level was up regulated.
      Moreover, spirotetramat affected the oocyte development especially on the
      diameter size and maturation during the ovary tissue biopsies at 28 days. Taken
      together, these findings revealed the adverse effects of spirotetramat on fish
      from the biochemical and histological aspects.

PMID- 30107325
TI  - Effects of microplastics and mercury in the freshwater bivalve Corbicula fluminea
      (Muller, 1774): Filtration rate, biochemical biomarkers and mercury
      bioconcentration.
AB  - The main objectives of this study were to investigate the effects of a mixture of
      microplastics and mercury on Corbicula fluminea, the post-exposure recovery, and
      the potential of microplastics to influence the bioconcentration of mercury by
      this species. Bivalves were collected in the field and acclimated to laboratory
      conditions for 14 days. Then, a 14-day bioassay was carried out. Bivalves were
      exposed for 8 days to clean medium (control), microplastics (0.13 mg/L), mercury
      (30 ug/L) and to a mixture (same concentrations) of both substances. The post
      exposure recovery was investigated through 6 additional days in clean medium.
      After 8 and 14 days, the following endpoints were analysed: the post-exposure
      filtration rate (FR); the activity of cholinesterase enzymes (ChE), NADP
      dependent isocitrate dehydrogenase (IDH), octopine dehydrogenase, catalase,
      glutathione reductase, glutathione peroxidase and glutathione S-transferases
      (GST), and the levels of lipid peroxidation (LPO). After 8 days of exposure to
      mercury, the bioconcentration factors (BCF) were 55 in bivalves exposed to the
      metal alone and 25 in bivalves exposed to the mixture. Thus, microplastics
      reduced the bioconcentration of mercury by C. fluminea. Bivalves exposed to
      microplastics, mercury or to the mixture had significantly (p <= 0.05) decreased
      FR and increased LPO levels, indicating fitness reduction and lipid oxidative
      damage. In addition, bivalves exposed to microplastics alone had significant (p
      <= 0.05) reduction of adductor muscle ChE activity, indicating neurotoxicity.
      Moreover, bivalves exposed to mercury alone had significantly (p <= 0.05)
      inhibited IDH activity, suggesting alterations in cellular energy production.
      Antagonism between microplastics and mercury in FR, ChE activity, GST activity
      and LPO levels was found. Six days of post-exposure recovery in clean medium was
      not enough to totally reverse the toxic effects induced by the substances nor to
      eliminate completely the mercury from the bivalve's body. These findings have
      implications to animal, ecosystem and human health.

PMID- 30107326
TI  - Sublethal or not? Responses of multiple biomarkers in Daphnia magna to single and
      joint effects of BDE-47 and BDE-209.
AB  - Polybrominated diphenyl ethers (PBDEs) are extremely incessant anthropogenic
      contaminants found in the environment, with dreadful risk to aquatic ecosystems.
      However, there is a limited amount of data concerning their impacts on freshwater
      organisms. 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) and
      2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are significant components of total
      PBDEs in water. The sublethal effects of BDE-47, BDE-209 and their binary
      mixtures on the aquatic organism Daphnia magna were investigated in acute and
      chronic exposure experiments. Immobilization and heartbeat were studied in
      daphnids after 48 h of exposure. Mortality rate, breed number, Cholinesterase
      (ChE), Glutathione S-transferases (GST) and Catalase (CAT) activities were
      evaluated after 21 days of exposure. The results showed that at 100 and 200 MUg/L
      concentration of BDE-47, immobilization rate of daphnids were inhibited by 44.0
      +/- 16.7% and 88.0 +/- 10.9%, respectively. The binary mixture of BDE-47 and BDE
      209 had uncongenial effects on immobilization of D. magna under acute toxicity
      test. BDE-209 significantly increased the heartbeat rate of daphnids, which
      increased even further when combined with BDE-47. After 21 days of exposure,
      daphnids exposed to single BDE-47 were physiologically altered. The combination
      of BDE-47 with BDE-209 significantly decreased the mortality rate of daphnids.
      Irrespective of the concentration, higher numbers of offsprings were produced in
      the mixtures compared to BDE-47 treatment alone. ChE activities significantly (p
      < 0.05) decreased at concentrations of 2 and 4 MUg/L in single BDE-47 treatment,
      while GST activity significantly (p < 0.05) decreased at 0.5 MUg/L. CAT
      activities significantly increased with BDE-47 treatments in all the tested
      concentrations (p < 0.05). The mixtures significantly affect ChE (p < 0.05), GST
      (p < 0.05) and CAT activities (p < 0.05). The results illustrated that the
      toxicity of the mixture of PBDE congeners exposed to aquatic organisms may have
      antagonistic effects. The 21 days chronic test in this study suggests that acute
      toxicity tests, i.e. 48-h tests, using Daphnia may lead to underestimation of
      risks associated with PBDEs, especially, BDE-209. Hence, there is a necessity to
      re-examine PBDE congeners' environmental risk in aquatic organisms.

PMID- 30107328
TI  - Early relaxation time assessment for characterization of breast tissue and
      diagnosis of breast tumors.
AB  - During recent years, many efforts have been made to increase the efficiency of
      the treatment methods by adjusting the treatment with the specification of
      related tissue. Non-penetrating indentation test is a non-invasive method for
      characterizing mechanical behavior of the tissue. In this study, characterization
      of the viscoelastic behavior of breast tissue is investigated by means of the
      relaxation time. To this end, an in-vivo study is conducted on the breast tissue
      of 18 female cases by performing a compressive indentation test with controlled
      rate of deformation. The test is performed in two subsequent stages; at first
      stage, the tissue is compressed by a specified strain rate and is called the
      loading procedure. At the second stage, which is the unloading procedure, the
      load is removed by the same rate and the tissue behavior is studied while it
      returns to the unloaded position. A generalized Maxwell model with two Maxwell
      arms is used to model the tissue's viscoelastic response. Force vs. compression
      data during the unloading course, are obtained and interpolated by the transfer
      function of the viscoelastic model and two relaxation times are obtained. The
      smaller in value is referred to as the early relaxation time and results show
      that it has variation with the tissue's mechanical structure, which makes it
      suitable as a characteristic property. This property has insignificant variation
      over each individual's breast tissue, meanwhile major variation is observed
      between different cases and also in the presence of a tumor. Results show that
      existence of tumor in the breast tissue can increase the early relaxation time up
      to 6 times more than the corresponding value at the healthy tissue. Based on case
      dependent character of the early relaxation time, tumor detection procedure based
      on the elevation of characteristic early relaxation time should be performed
      individually for each case.

PMID- 30107327
TI  - Impact of effective microorganisms on the transfer of radioactive cesium into
      lettuce and barley biomass.
AB  - Soil microorganisms play an important role in determining the physical and
      chemical properties of soils. Soil microorganisms have both direct and indirect
      effects on the physical and chemical states of radionuclides and their
      availability for uptake by plant roots. Controlling the soil microorganisms to
      immobilize radionuclides is a promising strategy to reduce the content of
      radionuclides in the food chain. In this study, we evaluated the impact of
      effective microorganisms (EM) comprising lactic-acid bacteria, photosynthetic
      bacteria, and yeast on the transfer of 137Cs into the aboveground biomass of
      barley and lettuce. The application of EM or fermented organic fertilizer
      (bokashi) alone to sod-podzolic sandy-loam soil significantly reduced the
      aggregated transfer factor of 137Cs in barley by 37% and 44%, respectively. The
      combination of EM with bokashi or potassium fertilizer produced the largest
      reductions in 137Cs transfer into barley biomass (50% and 63%, respectively). EM
      had a stronger effect on 137Cs transfer into barley compared to lettuce.
      Laboratory experiments suggested that the effect of microorganisms on 137Cs
      uptake can be attributed to a reduction in the proportion of bioavailable
      physicochemical forms of 137Cs in the soils treated with EM and bokashi. This
      study, to the best of our knowledge, is the first to report the mechanism by
      which microbial fertilizers reduce the transfer of 137Cs into plants.

PMID- 30107329
TI  - Postmortem analysis of three methoxyacetylfentanyl-related deaths in Denmark and
      in vitro metabolite profiling in pooled human hepatocytes.
AB  - Methoxyacetylfentanyl belongs to the group of fentanyl analogues and has been
      associated with several deaths in recent years. We present three case reports of
      deceased individuals that tested positive for methoxyacetylfentanyl consumption,
      as well as in vitro and in vivo metabolite profiles. Methoxyacetylfentanyl was
      quantified by ultra-high performance liquid chromatography-tandem mass
      spectrometry (UHPLC-MS/MS) in femoral blood, as well as in urine and brain tissue
      when these were available. Metabolite profiling was performed by incubating
      methoxyacetylfentanyl with pooled human hepatocytes (pHH) in Leibovitz's L-15
      medium supplemented with fetal bovine serum. Metabolites were identified in vivo
      and in vitro using UHPLC-high resolution (HR)-MS/MS. The measured
      methoxyacetylfentanyl concentration was 0.022-0.056mg/kg (N=3) in femoral blood,
      0.12mg/kg (N=1) in urine, and 0.074mg/kg (N=1) in brain tissue homogenate. A
      total of 10 metabolites were identified. The observed metabolic pathways were:
      hydroxylation(s), N-dealkylation, O-demethylation, deamination, glucuronidation,
      and combinations thereof. Major analytical targets in vitro and across measured
      biological samples in vivo were methoxyacetylfentanyl, the O-demethyl-
      metabolite, and the deamide-metabolite. Intoxication with methoxyacetylfentanyl
      was judged as the cause of death or a major contributing factor in all three
      presented cases.

PMID- 30107330
TI  - Multivariate linear intervention models with random parameters to estimate the
      effectiveness of safety treatments: Case study of intersection device program.
AB  - A novel intervention model that analyzes time-series crash data was recently
      introduced in the road safety statistical field. The model allows the computation
      of components related to direct and indirect treatment effects using a linearized
      time-series intervention model. The isolation of a component corresponding to the
      direct treatment effects, known as the crash modification function (CMFunction),
      enables the assessment of safety countermeasures over time. To gain new insights
      into how crash counts are influenced by covariates and to account for the fact
      that many components affecting crash occurrence are not easily available
      (unobserved heterogeneity), the linear intervention models with random parameters
      are implemented to evaluate the safety impacts of a specific treatment. Both
      matched-pair and full random parameter models were applied. In addition, the
      analysis was carried out in a multivariate context to account for possible
      correlation between dependent variables. The safety treatment selected for this
      study was the Intersection Safety Device (ISD) program implemented in the City of
      Edmonton (Alberta, Canada). The safety impacts were estimated by assessing the
      change in crash severity (property-damage-only vs. fatal-plus-injury) over time.
      Overall, the results showed a lower deviance information criterion (better
      goodness of fit) of the multivariate linear intervention model with random
      parameters compared to the univariate form with fixed parameters. The difference
      of the indexes of treatment effectiveness between the proposed modeling framework
      and the univariate model with fixed parameters was estimated up to 2.7%, which
      indicates the importance of accounting for unobserved heterogeneity.

PMID- 30107331
TI  - Accident severity levels and traffic signs interactions in state roads: a
      seemingly unrelated regression model in unbalanced panel data approach.
AB  - This study intended to investigate the interactions between accident severity
      levels and traffic signs in state roads located in Croatia, and explore the
      correlation within accident severity levels and heterogeneity attributed to
      unobserved factors. The data from 410 state roads between 2012 and 2016 were
      collected from Traffic Accident Database System maintained by the Republic of
      Croatia Ministry of the Interior. To address the correlation and heterogeneity, a
      seemingly unrelated regression (SUR) model in unbalanced panel data approach was
      proposed, in which the seemingly unrelated model addressed the correlation of
      residuals, while the panel data model accommodated the heterogeneity due to
      unobserved factors. By comparing the pooled, fixed-effects and random-effects SUR
      models, the random-effects SUR model showed priority to the other two. Results
      revealed that (1) low visibility and the number of invalid traffic signs per km
      increased the accident rate of material damage, death or injured; (2) average
      speed limit exhibited a high accident rate of death or injured; (3) the number of
      mandatory signs was more likely to reduce the accident rate of material damage,
      while the number of warning signs was significant for accident rate of death or
      injured.

PMID- 30107332
TI  - An investigation into electrochemical properties of poly(ether
      sulfone)/poly(vinyl pyrrolidone) heterogeneous cation-exchange membranes by using
      design of experiment method.
AB  - Poly(ether sulfone) (PES)/poly(vinyl pyrrolidone) (PVP) blend heterogeneous
      cation exchange membranes were prepared by solution casting technique using
      dimethylformamide as solvent and cation exchange resin powder as functional
      groups agent. In this study, Taguchi experiment design method was employed for
      investigating the effects of controlling variables including polymer binder (PVP
      + PES) to total casting solution ratio, blend ratio of polymer binders (PVP to
      PES), resin to polymer binder ratio, and casting temperature on electrochemical
      characteristics of PES/PVP heterogeneous membranes. To this aim, each factor was
      considered at 4 different levels and therefore, 16 experiments were designed. To
      improve the quality of the membranes ultrasonic was used for appropriate
      dispersing of resin particles in the matrix of the membranes. According to the
      results, the averaged maximum values of 1.535 meq/g and 46.6 mV were obtained for
      IEC and membrane potential, respectively. Also, the highest obtained value of ion
      permeability tests was equal to 1.33 m/s. Finally, the synthesis conditions was
      optimized by considering the IEC and membrane potential as the objective
      functions which gave the values of 1.55 meq/g and 1.39 m/s for IEC and membrane
      potential, respectively, which proved that the synthesized membrane can be
      considered as a promising heterogeneous membrane.

PMID- 30107333
TI  - Enhanced photocatalytic activity of CdS/SnS2 nanocomposite with highly-efficient
      charge transfer and visible light utilization for selective reduction of 4
      nitroaniline.
AB  - Photocatalytic reduction can be an effective and promising technology for the
      selective reduction of aromatic nitro organics. In this paper, a novel Z-scheme
      CdS/SnS2 photocatalyst was well-designed and fabricated via simple in-site
      reaction process containing thioacetamide as a sulfur sources and cubic CdSnO3 as
      template. The resulting CdS/SnS2 composite has well-constructed cubic
      nanostructure of strong adhesion between CdS and SnS2, presenting high absorption
      to visible light. Importantly, strong charge transfer between the contacting
      regions of CdS and SnS2 through the intermediate sulfur atoms combined with both
      metals was generated, which speeds up separation of photogenerated electron and
      hole. The advantageous combination of high light-harvesting and effective charge
      transfer is responsible for the excellent photocatalytic activity at the CdS/SnS2
      heterointerface. Resultantly, the prepared CdS/SnS2 composites exhibit high
      conversion efficiency and selectivity on 4-nitroaniline (4-NA) reduction in the
      aqueous solution containing ammonium formate under visible light irradiation,
      which can reduce almost all 4-NA within 12 min. Trapping experiments and ESR
      analysis demonstrated that ammonium formate not only can effectively decrease
      recombination of photogenerated charge carriers but also react with holes to
      generate CO2- radicals possessing strong reduction ability. The 4-NA are
      effectively photo-reduced by the synergistic effect of electrons and CO2-
      radicals. According to the experimental results, a possible Z-scheme charge
      transfer mechanism was proposed. Besides, the photo-reduction of aromatic nitro
      organics possessed different para-groups (p-nitrophenol, nitrobenzene, and p
      nitrobenzaldehyde) was also investigated. It is found that the electron-drawing
      group can decrease the electron density of its para-position nitryl, which
      quickens the nitro reduction.

PMID- 30107334
TI  - A naked mole rat iPSC line expressing drug-inducible mouse pluripotency factors
      developed from embryonic fibroblasts.
AB  - Naked mole rats (NMRs, Heterocephalus glaber) are long-lived, cancer-resistant
      rodents. Here, we report the development of an induced pluripotent stem cell
      (iPSC) line generated from immortalized NMR embryonic fibroblasts transduced with
      a doxycycline-inducible mouse OSKM polycistronic vector. This iPSC line was shown
      to express pluripotency-associated markers, form embryoid bodies, differentiate
      in vitro to the derivatives of three germ layers, and exhibit normal karyotype.
      The ability of iPSCs to differentiate in vivo was supported by the contribution
      to interspecific chimera upon injection into mouse blastocysts. This NMR iPSC
      line may be a useful tool in cancer and aging research.

PMID- 30107335
TI  - Multiple sclerosis prevalence in Salta City, Argentina.
AB  - INTRODUCTION: Multiple Sclerosis (MS) is one of the leading causes of disability
      in young adults. Its prevalence varies according to different countries. In
      Argentina there is a wide heterogeneity regarding data published in different
      areas of the country. Prevalence established in most studies is 17 cases per
      100,000 inhabitants; however, most of the available data comes from studies that
      took place in Buenos Aires. There is little or no information from other
      provinces, especially from Northwest of Argentina (NOA), where there are no
      studies of the disease prevalence. The aim of this study is to investigate MS
      prevalence, phenotypes and epidemiological characteristics in Salta, Argentina,
      in order to contribute to the current knowledge of MS epidemiology and
      distribution in our country. METHODS: A descriptive, observational, transversal
      study was carried out in the capital city of Salta. Researchers from all public
      and private hospitals with a Neurology Department have participated. Private
      researchers who are well known leaders in demyelinating diseases in the city
      provided valuable information. Patients who did not have medical control for the
      past two years as well as patients whose last address was not registered in Salta
      were excluded. RESULTS: 120 registries were obtained from the four hospitals that
      participated and from the 12 private researchers. Ten patients were excluded due
      to overlapping data. The population of the area based on 2010 census was 535,310,
      so we estimated an MS prevalence 23.8 cases per 100,000 inhabitants (95% CI 20.1
      27.4), 24.1 cases per 100,000 inhabitants in female population (95% CI 21.2-28.6)
      and 18.2 cases per 100,000 inhabitants (95% CI 15.2-21.1) in male population. In
      our analysis, 64 (58.2%) were female and the average age was 42.1 years. 81.8%
      are recurrent remitting forms, 16.4% secondary progressive and 1.8% primary
      progressive. CONCLUSION: This is the first study that provides epidemiological
      data on the prevalence and clinical forms of MS in Salta City as well as in the
      entire Northwest Region of Argentina(NOA). We estimate a prevalence of 23.8 cases
      per 100,000 inhabitants, which establishes a moderate risk area for MS.

PMID- 30107336
TI  - Bioprinting of glioma stem cells improves their endotheliogenic potential.
AB  - Glioblastoma (GBM), with rich blood vessels and high invasiveness, is the most
      common malignant primary brain tumor. The current treatment strategies are less
      effective, resulting in tumor recurrence. Tumor angiogenesis plays an important
      role in the occurrence, development and metastasis of GBM. Currently, GBM has
      been treated by inhibiting tumor angiogenesis. In-depth study of tumor
      angiogenesis is of great significance for the treatment of GBM. Recent studies
      have shown that glioma stem cells (GSCs) are involved in tumor vascularization by
      secreting vascular endothelial growth factor (VEGF). It is necessary to construct
      an ideal in vitro model to study the mechanism of GSCs in tumor vascularization.
      Here we used extrusion-based three-dimensional (3D) bioprinting technology to
      fabricate GSCs tumor model. In this study, the viability of cells after
      bioprinting was 86.27 +/- 2.41%. Furthermore, compared with traditional
      suspension culture, the proliferation of 3D printed GSCs was more stable. Through
      the transmission electron microscopy (TEM), numerous long microvilli of cells
      cultured in 3D bioprinted scaffolds were observed. 3D bioprinted GSCs also have
      more abundant mitochondria and rough endoplasmic reticulum. Additionally, the
      stemness properties, the expression of tumor angiogenesis-related genes and
      vascularization potential of 3D bioprinted GSCs in vitro were higher than that of
      suspension cultured cells. In summary, 3D bioprinted cell-laden hydrogel
      scaffolds provide a proper model for investigating the biological characteristics
      of GSCs and tumor angiogenesis.

PMID- 30107337
TI  - Angiopep-2 modified PEGylated 2-methoxyestradiol micelles to treat the PC12 cells
      with oxygen-glucose deprivation/reoxygenation.
AB  - 2-Methoxyestradiol (2ME2), as a microtubule and hypoxia-inducible factor-1 (HIF
      1) inhibitor, can be used to treat cerebral ischemia-reperfusion (I/R) injury.
      However, its poor water solubility compromises its efficacy as a neuroprotectant.
      Herein, we synthesized PEGylated 2ME2 and angiopep-2 capped PEGylated 2ME2 and
      fabricated angiopep-2 modified PEGylated 2ME2 micelles containing free 2ME2 (ANG
      PEG-2ME2/2ME2) via emulsion-solvent evaporation method. The effect of the
      micelles on ischemia-reoxygenation injury was evaluated by oxygen-glucose
      deprivation/reoxygenation (OGD/R) models with different degrees of PC12 cell
      damage. In comparison with free 2ME2, the micelles significantly increased the
      cell viability, inhibited reactive oxygen species (ROS) generation and apoptosis
      for PC12 cells with 0.5 and 4 h OGD followed by 24 h reoxygenation. Taken
      together, the angiopep-2 modified 2ME2-loaded micelles could effectively reduce
      the injury of PC12 cells induced by OGD/R.

PMID- 30107338
TI  - Electrostatic and hydrophobic controlled self-assembly of PDMS-E grafted gelatin
      for self-cleaning application.
AB  - Understanding the assembly mechanisms of supramolecular architectures in nature
      is essential for the design and synthesis of novel biomaterials. In the work,
      self-assembly of gelatin-mono epoxy terminated polydimethylsiloxane polymer (PGG)
      controlled by electrostatic and hydrophobic interactions between gelatin and
      sodium dodecyl sulfate (SDS) was investigated in suit. Confocal laser scanning
      microscopy, circular dichroism spectroscopy, high-resolution transmission
      electron microscopy and X-ray photoelectron spectroscopy were conducted to reveal
      the structure evolution of PGG at a molecular level with the increment of SDS
      concentration, including micro-sized sphere, core-shell and multi-layer
      structure. Notably, the multi-layer structure was formed from the large
      contribution of antiparallel beta-sheets on the boundary and new hydrophobic
      aggregation driven by higher monomer conversions. The delicate supramolecular
      architectures preliminarily present excellent anti-water, anti-contamination and
      anti-radiation properties in the surface of skin. The excellent self-cleaning
      function of PGG indicates potential application in biomaterials.

PMID- 30107339
TI  - Development and characteristics nanoscale retrograded starch as an encapsulating
      agent for colon-specific drug delivery.
AB  - Retrograded starch (RS III) decreased into nanoscale particles through high-speed
      shearing emulsification, and the unknown effects of shear speed and shear time on
      their particle size were explored in this study. The in vitro digestibility,
      structure properties, stability, and adsorption property of these nanoparticles
      were also determined. The prepared RS III nanoparticles showed notches and
      grooves on the surface, and measured an average size of approximately 300 nm with
      high luminosity. Resistant starch contents decreased, while in vitro
      digestibility results suggested that these nanoparticles still exhibited high
      resistance to digestion, indicating that RS III nanoparticles were suitable for
      colon-specific drug delivery as an encapsulating agent. FTIR, Raman and XRD
      experiments indicated that these nanoparticles possessed new peaks and an
      amorphous structure. RS III nanoparticles were found to be most stable in
      increased pH or decreased NaCl concentration. Moreover, RS III nanoparticles
      exhibited high adsorption capacities and long in vitro release properties for 5
      fluorouracil with loading capacity and encapsulation efficiency of 49.20 mg/g and
      49.25%, respectively.

PMID- 30107340
TI  - Controllable and durable release of BMP-2-loaded 3D porous sulfonated
      polyetheretherketone (PEEK) for osteogenic activity enhancement.
AB  - Polyetheretherketone (PEEK) is ideal for dental and orthopedic applications
      because its mechanical properties are similar to cortical bones. However, its
      inherent inert ability hinders its clinical applications. In this work, bone
      morphogenetic protein-2 (BMP-2) was immobilized onto the sulfonated PEEK (SPEEK)
      using lyophilization technology. The surface morphologies of the samples were
      analyzed by field-emission scanning electron microscopy (FE-SEM), and the
      chemical compositions were analyzed by energy-dispersive X-ray spectrometry
      (EDS). The release content of BMP-2 of the samples immersed in the PBS (pH = 7.4)
      was detected by a human BMP-2 ELISA kit. The results indicated that controllable
      and durable BMP-2 release was accomplished due to the three-dimensional (3D)
      network of sulfonated PEEK. The in vitro cellular experiments showed that the BMP
      2-immobilized samples significantly enhanced the initial adhesion and spreading
      of rat bone mesenchymal stem cells (rBMSCs). Moreover, the collagen secretion,
      extracellular matrix mineralization and ALP activity were also improved. Thus,
      the BMP-2-immobilized samples greatly promoted the osteogenic differentiation of
      rBMSCs, which revealed that BMP-2 immobilization paves the way for the use of
      PEEK in clinical applications.

PMID- 30107341
TI  - 3-hydroxycoumarin loaded vesicles for recombinant human tyrosinase inhibition in
      topical applications.
AB  - Tyrosinase is one of the key enzymes in mammalian melanin biosynthesis.
      Decreasing tyrosinase activity has been targeted for the prevention of conditions
      related to the hyperpigmentation of the skin, such as melasma and age spots. This
      paper is devoted to the engineering of vesicle formulations loaded with 3
      hydroxycoumarin for topical pharmaceutical applications. At first, it was
      demonstrated the strong inhibiting ability of 3-hydroxycoumarin against
      recombinant human tyrosinase. Then, such a drug was effectively encapsulated
      within liquid or gel-like vesicle formulations, both based on monoolein and
      lauroylcholine chloride. In vitro skin penetration and permeation studies proved
      these formulations efficiently overcome the barrier represented by the stratum
      corneum, delivering 3-hydroxycoumarin to the deeper skin layers. The effect of
      applying for different times the liquid and the gel formulation was also
      evaluated. Results revealed that application of the gel formulation for 2 h
      favored the drug accumulation into the skin with low transdermal delivery, thus
      indicating this combination of administration time and formulation as ideal to
      locally inhibit tyrosinase activity with minimal systemic absorption. Moreover,
      when incubated with B16F10 melanoma cells, the liquid vesicle formulations did
      not show cytotoxic activity.

PMID- 30107342
TI  - Cytotoxicity of AMANTADIG - a semisynthetic digitoxigenin derivative - alone and
      in combination with docetaxel in human hormone-refractory prostate cancer cells
      and its effect on Na+/K+-ATPase inhibition.
AB  - Cardiac glycosides (CGs) are natural compounds used to treat congestive heart
      failure. They have garnered attention as a potential cancer treatment option,
      especially because they bind to Na+/K+-ATPase as a target and activate
      intracellular signaling pathways leading to a variety of cellular responses. In
      this study we evaluated AMANTADIG, a semisynthetic cardenolide derivative, for
      its cytotoxic activity in two human androgen-insensitive prostate carcinoma cell
      lines, and the potential synergistic effects with docetaxel. AMANTADIG induced
      cytotoxic effects in both cell lines, and a combination with docetaxel showed a
      moderate and strong synergism in DU145 and PC-3 cells, respectively, at
      concentrations considerably lower than their IC50 values. Cell cycle analyses
      showed that AMANTADIG and its synergistic combination induced G2/M arrest of
      DU145 and PC-3 cells by modulating Cyclin B1, CDK1, p21 and, mainly, survivin
      expression, a promising target in cancer therapy. Furthermore, AMANTADIG
      presented reduced toxicity toward non-cancerous cell type (PBMC), and
      computational docking studies disclosed high-affinity binding to the Na+/K+
      ATPase alpha subunit, a result that was experimentally confirmed by Na+/K+-ATPase
      inhibition assays. Hence, AMANTADIG inhibited Na+/K+-ATPase activity in PC-3
      cells, as well as in purified pig kidney at nanomolar range. Altogether, these
      data highlight the potent effects of AMANTADIG in combination with docetaxel and
      offer important insights for the development of more effective and selective
      therapies against prostate cancer.

PMID- 30107343
TI  - Identification of N-Hydroxycinnamamide analogues and their bio-evaluation against
      breast cancer cell lines.
AB  - The present study demonstrates the identification of N-hydroxycinnamamide
      derivatives and their anticancer potential against human triple-negative breast
      cancer cell line MDA-MB-231, MCF-7 and non-malignant origin cell line, HEK-293
      (human embryonic kidney). MTT assay was studied with HEK-293 cell line.
      Anticancer potential of the N-hydroxycinnamamide derivatives were compared with
      marked drug Tamoxifen through in vitro study. The compound numbers 3b and 3h
      exhibit most potent activity against antagonistic breast cancer cells (MDA-MB
      231) with IC5013MUM and 5MUM respectively. Compound 3h promotes DNA fragmentation
      and induction of apoptosis. Furthermore, loss of mitochondrial membrane potential
      induced by compound 3h. The major mechanism of compound 3h for anti-breast cancer
      activity was probably initiation of reactive oxygen species (ROS) in cancer cells
      thereby persuading apoptotic cell deaths in cancer cells.

PMID- 30107344
TI  - Resveratrol inhibits proliferation, migration and invasion of multiple myeloma
      cells via NEAT1-mediated Wnt/beta-catenin signaling pathway.
AB  - PURPOSE: To study the influence of resveratrol on proliferation, migration and
      invasion of multiple myeloma (MM) cells through the long noncoding RNA (lncRNA)
      NEAT1 (nuclear enriched abundant transcript 1)-modulated Wnt/beta-catenin
      signaling pathway. METHODS: Microarray analysis was used to screen aberrantly
      expressed lncRNAs from MM cells and normal plasmocytes. The effects of NEAT1
      overexpression/silencing or resveratrol treatment on MM cell (U266 and LP1)
      proliferation, migration and invasion were investigated using CCK-8 (Cell
      Counting Kit-8), wound healing and Transwell invasion assays. Expression of
      Wnt/beta-catenin related proteins and unfolded protein response (UPR)-related
      proteins was detected by western blot. RESULTS: lncRNA NEAT1 was highly expressed
      in MM cells, which could be significantly inhibited by resveratrol. NEAT1
      overexpression induced proliferation, migration and invasion of MM cells, while
      resveratrol counteracted its effect. NEAT1 upregulated protein expression in the
      Wnt/beta-catenin signaling pathway, while resveratrol reversed the negative
      effect of NEAT1 overexpression on MM cells through the Wnt/beta-catenin signaling
      pathway, and hence suppressed MM cell reproduction, migration and invasion.
      Resveratrol could also restrain unfolded protein response in MM cells.
      CONCLUSION: Resveratrol downregulated the expression of lncRNA NEAT1 in MM cells
      and inhibited proliferation, migration and invasion of MM cells by suppressing
      the Wnt/beta-catenin signaling pathway and unfolded protein response.

PMID- 30107345
TI  - Diffusion-ordered spectroscopy on a benchtop spectrometer for drug analysis.
AB  - The first reported two-dimensional diffusion-ordered spectroscopy (DOSY)
      experiments were recorded at low field (LF) on a benchtop NMR spectrometer using
      the BPP-STE-LED (bipolar pulse pair-stimulated echo sequence with a longitudinal
      eddy current delay) pulse sequence which limits phase anomalies and baseline
      discrepancies. A LF DOSY map was first obtained from a solution of a model
      pharmaceutical formulation containing a macromolecule and an active
      pharmaceutical ingredient. It revealed a clear separation between the components
      of the mixture and gave apparent diffusion coefficients (ADC) values consistent
      with those measured from the reference high field experiment. LF DOSY was then
      applied to a real esomeprazole medicine and several gradient sampling schemes
      (linear, exponential and semi-gaussian (SG)) were compared. With a pulsed field
      gradient range of 4-70%, the most reliable results were given by the SG ramp. The
      resulting LF DOSY map obtained after 2.84 h of acquisition confirmed that the
      diffusion dimension is of prime interest to facilitate the assignment of
      overcrowded LF spectra although relevant ADC values could not be obtained in part
      of the spectrum with highly overlapped signals.

PMID- 30107346
TI  - MiR-137 suppresses tumor growth and metastasis in clear cell renal cell
      carcinoma.
AB  - BACKGROUND: The most frequent type of renal cell carcinoma is called clear-cell
      renal cell carcinoma (ccRCC) which is associated with a poor prognosis. It has
      been observed that miR-137 is aberrantly expressed in many different kinds of
      human malignancies including ccRCC. This research aims to examine the role of miR
      137 in ccRCC. METHODS: Quantitative RT-PCR (qRT-PCR) was applied to measure miR
      137 expression in ccRCC and adjacent noncancerous tissue. Gene expression was
      determined by western blot. Cell Counting Kit-8 (CCK-8) assay, flow cytometry and
      Transwell assay were used to determine the effects of miR-137 on cell growth,
      apoptosis and invasion, respectively. Moreover, xenograft and pulmonary
      metastasis animal models were established to investigate the role of miR-137 in
      vivo. RESULTS: Our findings show that there was significant downregulation of miR
      137 in ccRCC tissue relative to corresponding non-cancerous tissue. Ectopic miR
      137 expression in ccRCC cells led to suppression of cell growth and invasion, as
      well as apoptosis induction. In contrast, knockdown of miR-137 enhances
      proliferation and invasion, inhibits apoptosis. It also confirms that miR-137
      plays a tumor supressor role in vivo. Mechanically, miR-137 directly targets the
      3'-UTR of RLIP76 which is an established oncogene in ccRCC. CONCLUSION: MiR-137
      serves as a tumor suppressor, which can be considered a potential therapeutic
      target in ccRCC.

PMID- 30107347
TI  - Drug-drug interaction potential of antitumor acridine agent C-1748: The substrate
      of UDP-glucuronosyltransferases 2B7, 2B17 and the inhibitor of 1A9 and 2B7.
AB  - BACKGROUND: The compound 9-(2'-hydroxyethylamino)-4-methyl-1-nitroacridine (C
      1748), the promising antitumor agent developed in our laboratory was determined
      to undergo phase I metabolic pathways. The present studies aimed to know its
      biotransformation with phase II enzymes - UDP-glucuronosyltransferases (UGTs) and
      its potential to be engaged in drug-drug interactions arising from the modulation
      of UGT activity. METHODS: UGT-mediated transformations with rat liver (RLM),
      human liver (HLM), and human intestine (HIM) microsomes and with 10 recombinant
      human isoenzymes were investigated. Studies on the ability of C-1748 to inhibit
      UGT were performed with HLM, HT29 colorectal cancer cell homogenate and the
      selected recombinant UGT isoenzymes. The reactions were monitored using HPLC
      UV/Vis method and the C-1748 metabolite structure was determined with ESI-TOF
      MS/MS analysis. RESULTS: Pseudo-molecular ion (m/z 474.1554) and the experiment
      with beta-glucuronidase indicated that O-glucuronide of C-1748 was formed in the
      presence of microsomal fractions. This reaction was selectively catalyzed by
      UGT2B7 and 2B17. High inhibitory effect of C-1748 was shown towards isoenzyme
      UGT1A9 (IC50=39.7MUM) and significant but low inhibitory potential was expressed
      in HT29 cell homogenate (IC50=84.5MUM). The mixed-type inhibition mechanism
      (Ki=17.0MUM;Ki'=81.0MUM), induced by C-1748 was observed for recombinant UGT1A9
      glucuronidation, whereas HT29 cell homogenate resulted in noncompetitive
      inhibition (Ki=94.6MUM). CONCLUSIONS: The observed UGT-mediated metabolism of C
      1748 and its ability to inhibit UGT activity should be considered as the potency
      for drug resistance and drug-drug interactions in the prospective multidrug
      therapy.

PMID- 30107348
TI  - Curcumin affects tracheal responsiveness and lung pathology in asthmatic rats.
AB  - BACKGROUND: Curcumin has shown various pharmacological effects such as anti
      inflammatory activities. In this study, the effects of curcumin on tracheal
      responsiveness and lung pathological features were evaluated in a rat model of
      asthma. METHODS: Tracheal responsiveness and lung pathological features were
      evaluated in control rats (C), ovalbumin (OVA)-sensitized rats (as an animal
      model of asthma; A), A rats treated with curcumin (Cu, 0.15, 0.30, and 0.60mg/ml)
      and dexamethasone (D, 1.25MUg/ml), (n=8 in curcumin-treated groups and n=6 in
      other groups). Curcumin and dexamethasone were added to animals' drinking water
      during the sensitization period. RESULTS: Asthmatic group showed increased lung
      pathological score and tracheal responsiveness to methacholine and OVA compared
      to control group (p<0.01 to p<0.001). Pathological features including
      interstitial inflammation, interstitial fibrosis, bleeding, and emphysema as well
      as tracheal responsiveness to methacholine and OVA, were significantly decreased
      in treated groups with dexamethasone and all concentrations of curcumin compared
      to group A (p<0.05 to p<0.001). Epithelial damage was also significantly
      decreased in treated groups with the two higher concentrations of curcumin
      (p<0.05 to p<0.001). CONCLUSION: Curcumin showed preventive effects on tracheal
      responsiveness and lung pathological features in asthmatic rats.

PMID- 30107349
TI  - Octanoic acid prevents reduction of striatal dopamine in the MPTP mouse model of
      Parkinson's disease.
AB  - BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative process
      leading to the loss of dopaminergic neurons and their projections. 1-methyl-4
      phenol-1,2,5,6-tetrahydropyridine (MPTP) toxicity is a well-recognized animal
      model of PD. It is suggested that the impairment of mitochondrial function in the
      substantia nigra plays an important role in both the onset and the progression of
      PD. Octanoic acid (C8), a fatty acid that is the main constituent of the medium
      chain triglyceride ketogenic diet, increases the metabolic activity of
      mitochondria; hence, it seemed interesting to investigate whether C8 exhibits
      neuroprotective effects in the MPTP model of PD and whether it affects
      mitochondria function in the striatum. METHODS: Therefore, we examined the
      possible protective effects of C8 in the mouse model of PD induced by MPTP. For
      this purpose, changes in the concentration of DA and its metabolites were
      determined. In addition, we investigated whether expression levels of PGC-1alpha
      and the PEPCK enzyme, markers of mitochondrial activity, are altered by C8.
      RESULTS: In this study, we observed for the first time that acute and, in
      particular, repeated administrations of C8 significantly reduced the impairment
      of dopaminergic neurotransmission in the striatum evoked by MPTP administration
      and resulted in a marked increase in PGC-1alpha expression and in both forms of
      PEPCK. CONCLUSIONS: These results indicate that the C8 leads to an inhibition of
      the neurodegenerative processes seen after MPTP administration. Our results
      suggest that a probable mechanism of the neuroprotective action of C8 is related
      to an increase in metabolic activity in striatal mitochondria.

PMID- 30107350
TI  - Ketamine augmentation for major depressive disorder and suicidal ideation:
      Preliminary experience in an inpatient psychiatry setting.
AB  - BACKGROUND: Ketamine is known to rapidly reduce depressive symptoms and suicidal
      ideation (SI) in patients with major depressive disorder (MDD), but evidence is
      limited for its acceptability and effectiveness in "real-world" settings. This
      case series examines serial ketamine infusions in reducing SI and depression
      scores in adults with MDD admitted to a tertiary care hospital. METHODS: Five
      inpatients with MDD and SI admitted to hospital in Toronto, Canada received six
      infusions of 0.5 mg/kg intravenous (IV) ketamine (n = 5) over approximately 12
      days, in addition to treatment-as-usual. Suicide and depression rating scores
      (Scale for Suicidal Ideation, SSI; Montgomery-Asberg Depression Rating Scale,
      MADRS) were obtained at baseline, on treatment days, on days 14 and 42 (primary
      endpoint). RESULTS: All patients experienced benefit with ketamine. SSI scores
      diminished by 84% from 14.0 +/- 4.5 at baseline to 2.2 +/- 2.5 at study endpoint.
      MADRS scores diminished by 47% from 42.2 +/- 5.3 at baseline to 22.4 +/- 8.0. Two
      patients withdrew from the study, one to initiate electroconvulsive therapy and
      one due to an adverse event (dissociative effects) during the ketamine infusion.
      LIMITATIONS: The major limitation of this study is the small sample size.
      DISCUSSION: These preliminary pilot data are promising with a greater than two
      fold reduction in SI following ketamine infusions. They demonstrate that six
      serial ketamine infusions may be safe and feasible. These findings support the
      need for large scale randomized controlled trials to confirm the efficacy of
      serial ketamine for treatment of SI in "real-world" settings.

PMID- 30107351
TI  - Loss experiences in old age and their impact on the social network and depression
      results of the Leipzig Longitudinal Study of the Aged (LEILA 75+).
AB  - BACKGROUND: Loss experiences and bereavement are common among the oldest old.
      This study aims to investigate the effects of loss experiences and the social
      network type on depression in old age. METHODS: As part of the Leipzig
      Longitudinal Study of the Aged (LEILA 75+), a representative population-based
      cohort study, 783 persons aged 75+ years were assessed via standardized
      interviews including the Practitioner Assessment of Network Type Instrument
      (PANT) and the Center for Epidemiologic Studies-Depression Scale (CES-D). Effects
      of loss experiences and network type on depression were analysed cross
      sectionally (baseline survey) using logistic regressions. Effects over time were
      analysed longitudinally (follow-up1 and follow-up2) using hybrid techniques.
      RESULTS: More than half of the elderly (57%) continuously lived in a restricted
      network. Only 12.1% lived in an integrated network. Although 30.9% had a change
      in their network, no significant association with loss experiences was found.
      Nevertheless, loss experiences (OR 7.56 (1.60-35.72)) and a restricted social
      network (OR 4.08 (1.52-10.95)) appeared to be the significant predictors of
      depression. LIMITATIONS: Our study captures only a selected time window of the
      individual life and loss experience was only assessed at the time of the baseline
      survey. CONCLUSION: Our findings revealed that elderly individuals, who
      experienced social loss or lived in restricted social networks, were more likely
      to develop depression compared to individuals who lived in integrated social
      networks or without loss experiences. The social integration of elderly
      individuals is an urgent issue that should be addressed in order to reduce
      depression in old age.

PMID- 30107352
TI  - Clinical diagnostic utility of contrast-enhanced three-dimensional fluid
      attenuated inversion recovery for selection of brain biopsy sites in
      neurosarcoidosis: A case report.
AB  - Neurosarcoidosis is difficult to diagnose, because definite diagnosis requires
      detailed histology of the central nervous system. Three-dimensional contrast
      enhanced fluid-attenuated inversion recovery (CE-FLAIR) is more useful for
      detecting leptomeningeal lesions compared with 3D CE-T1 weighted imaging.
      However, the clinical diagnostic utility of 3D CE-FLAIR for neurosarcoidosis is
      unclear. We describe a case of a 46-year-old Japanese woman who was admitted to
      our department due to chronic headache with fever and diplopia. Using 3D CE
      FLAIR, we performed brain biopsy from right cerebellar lesion. The histological
      examination revealed typical non-caseating granulomas, indicating
      neurosarcoidosis. Our findings suggest that 3D CE-FLAIR may detect leptomeningeal
      lesions that are candidates for biopsy in chronic meningitis undetermined
      etiology.

PMID- 30107353
TI  - Operator radiation doses during CT-guided spine procedures.
AB  - OBJECTIVES: To perform a pilot study to quantify the radiation dose incident on
      operators during CT-guided interventional spine procedures, and provide a quick
      method to approximate it based on the total amount of radiation reported by the
      CT scanner. PATIENTS AND METHODS: Data retrospectively obtained from 26
      consecutive CT-guided spine procedures, encompassing a variety of interventions.
      Intermittent low-dose limited-coverage CT-scanning performed using a "step and
      shoot" mode to visualize needle advancement. The operator wore an electronic
      direct dosimeter to record the dose measured above the operator's lead apron
      [MUGy] for each procedure. Total amount of radiation used for CT-guidance
      quantified by the Dose-Length Product (DLP) [mGy-cm] provided by the CT scanner.
      The relationship between the operator's dose and the DLP was assessed. RESULTS:
      Average and median operator's dose were 2.3 and 1.9 MUGy, respectively, with half
      of these values ranging between 0.7 and 2.5 MUGy. Average and median DLP values
      used to perform the CT-guided procedure were 58 and 54 mGy-cm respectively, and
      half of these values ranged between 38 and 68 mGy-cm. There was a statistically
      significant correlation between the operator's dose and the DLP used to perform
      CT-guidance (r = 0.61), with an operator's dose-DLP conversion factor of 0.04
      MUGy / 1 mGy-cm (range: 0.006-0.083 MUGy / 1 mGy-cm). CONCLUSIONS: In our series,
      the average amount of radiation used during CT guided procedures was about 50 mGy
      cm (DLP), and the corresponding average operator's dose was about 2 MUGy. We
      showed how an approximate estimate of the operator's dose could be obtained right
      after each procedure, based on the CT-scanner DLP output.

PMID- 30107354
TI  - Therapeutic strategies for residual or recurrent intracranial aneurysms after
      microsurgical clipping.
AB  - OBJECTIVES: Therapeutic strategies for residual or recurrent aneurysm (RRA) after
      microsurgical clipping have not been well established. The purpose of this study
      was to report our retreatment experiences with previously clipped aneurysms and
      to demonstrate retreatment strategies for these RRAs. PATIENTS AND METHODS: From
      1996-2016, we treated 68 RRAs after previous clipping. Among them, 34 patients
      underwent microsurgical retreatment, and the other 34 underwent endovascular
      retreatment. Radiographic images and clinical data were reviewed retrospectively
      to determine the treatment efficacy, clinical outcomes, and important factors for
      selecting the proper treatment modality. RESULTS: The most common aneurysm
      location was the middle cerebral artery (50%) in the microsurgery group and the
      internal carotid artery (47.1%) in the endovascular surgery group (p =  0.001).
      In the microsurgery group, 16 (47.1%) patients had additional clipping without
      removal of previous clips, 17 (50.0%) had clipping with removal of previous
      clips, and 1 (2.9%) had bypass surgery with trapping. In the endovascular surgery
      group, 28 (82.4%) patients had simple coiling, 5 (14.7%) had stent-assisted
      coiling, and 1 (2.9%) had a flow diverter. Procedure-related complications during
      retreatment occurred in 4 (5.9%) patients. Complete obliteration was achieved in
      51 (75.0%) patients (microsurgery group, 82.4% and endovascular surgery group,
      67.6%; p =  0.002). CONCLUSIONS: In properly selected cases, treatment of RRAs
      could be safely performed either by microsurgery or endovascular surgery and
      result in a good clinical outcome with acceptable morbidity. The decision to
      choose the treatment modality for RRAs after clipping is not easy but should be
      considered to lower the risk of retreatment.

PMID- 30107355
TI  - Pott's puffy tumor presenting as a frontal swelling under a Swiss army helmet.
AB  - In this report, we describe an uncommon presentation of a Pott's puffy tumor,
      which is defined as a subperiosteal abscess related to a chronic frontal
      sinusitis. This condition has become rare in our part of the world because of the
      widespread use of antibiotics. Clinical history, investigations, and management
      are presented.

PMID- 30107356
TI  - Cytotoxic and genotoxic effects of antihypertensives distributed in Brazil by
      social programs: Are they safe?
AB  - Hypertension, a chronic non-transmissible multifactorial condition, it is highly
      frequent in Brazil, affecting about 32.5% of the population over 25 years of age.
      It is characterized by the sustained increase in systolic and diastolic blood
      pressure levels above 140 mmHg and 90 mmHg, respectively. It is the major
      aggravating factor in cardiovascular complications and the appearance of other
      comorbidities. Aiming to promote greater adherence to treatment and improve the
      population's access to basic medicament, in 2004 the Federal Government created
      the Programa Farmacia Popular do Brasil (PFPB); partnership with private
      institutions that provides the population with medicament to control
      hypertension, free of charge or subsidized at up to 90% of the value. The PFPB
      distributes the anti-hypertensives atenolol, captopril, enalapril,
      hydrochlorothiazide, losartan and propranolol. In this way, this work aims to
      evaluate the genotoxic potential of antihypertensives in human lymphocytes and
      macrophages, since they are widely used drugs and with few studies about their
      genotoxicological safety. The tests were developed from cell cultures treated
      with five different antihypertensive concentrations, all based on plasma peaks,
      evaluating cell viability, DNA damage index and DNA double strand breakdown. The
      results show that, as the concentration of captopril and enalapril maleate
      increased, cell viability decreased. In addition, a DNA damage was observed with
      the use Captopril and Enalapril in the higher concentrations. Hydrochlorothiazide
      also caused DNA damage in the five doses tested. Regarding the breaking of double
      strands of DNA, all the compounds showed increased ruptures. This decrease in
      dsDNA is dose dependent for all compounds tested. The set of results shows that
      the use although frequent still requires care and greater knowledge. In general,
      the antihypertensive drugs that proved to be safer in relation to the genetic
      damage tested were Losartan and Propranolol.

PMID- 30107357
TI  - Characterization and variation of microbial community structure during the
      anaerobic treatment of N, N-dimethylformamide-containing wastewater by UASB with
      artificially mixed consortium.
AB  - A lab-scale UASB was operated successfully to anaerobically treat wastewater
      containing approximately 2000 mg L-1N, N-dimethylformamide (DMF) by artificially
      mixing anaerobic granular sludge with DMF-degrading activated sludge. DMF was
      effectively degraded by the UASB under a low OLR of 1.63-4.22 g COD L-1 d-1, with
      over 96% DMF removal efficiency and a high methane production rate. However, the
      DMF-degrading ability gradually weakened along with increases in the OLR. The
      analysis of the microbial community structure by high-throughput sequencing
      revealed a decline in the abundance of the facultatively anaerobic DMF
      hydrolyzing bacteria originating from activated sludge with increasing OLR,
      further deteriorating the methanogenic degradation of DMF. When the OLR was
      lowered again, the slow growth of those facultative anaerobes recovered, and
      slight improvements in the removal were noted. Methylotrophic methanogens
      utilized the intermediate products from the hydrolysis of DMF, which kept
      increasing in abundance throughout the entire experimental period.

PMID- 30107358
TI  - Comparative investigation of rice husk, thermoplastic bituminous coal and their
      blends in production of value-added gaseous and liquid products during
      hydropyrolysis/co-hydropyrolysis.
AB  - The hydropyrolysis/co-hydropyrolysis of rice husk (RH) and thermoplastic
      bituminous coal (BC) was carried out using a fixed-bed reactor to investigate the
      effects of atmosphere and hydrogen pressure on product distributions. RH produced
      more carbon oxides, phenolics and acids. BC yielded more methane and BTX
      (benzene, toluene and xylene) during hydropyrolysis. Compared with hydropyrolysis
      of RH, the co-hydropyrolysis promoted the higher heating value of gaseous product
      and the yield of BTX by 19% and 57% respectively, while it reduced the yield of
      corrosive acids by 89% under 5 MPa H2. The yields of methane, BTX and phenolics
      during co-hydropyrolysis were 1.5, 6.4 and 4.0 times as much as those obtained
      during co-pyrolysis under 5 MPa. The co-hydropyrolysis reformed the structure of
      heavy oil/tar, benefiting the development of aromaticity. High hydrogen pressure
      synergistically reduced yields of char and acids, and enhanced yields of tar and
      light aromatics via the secondary reactions.

PMID- 30107359
TI  - Sorption of methyl orange from aqueous solution by protonated amine modified
      hydrochar.
AB  - The protonated amine modified hydrochar (PAMH) was synthesized by etherification,
      amination and protonated reaction with hydrochar, which was enriched with
      abundant protonated amine for methyl orange (MO) removal. PAMH was characterized
      by elemental analysis, scanning electron microscopy, nitrogen adsorption
      desorption measurement, zeta potential and Fourier transform infrared. The
      sorption of MO from aqueous solution by PAMH was investigated by batch
      experiments. The results showed that sorption of MO was significantly influenced
      by the initial concentration of MO, temperature, contact time and ionic strength,
      while hardly affected by pH values ranging from 4 to 11. The pseudo-second-order
      and Langmuir equations were able to depict sorption kinetics and sorption
      isotherms, respectively. Thermodynamic analysis indicated that the sorption
      behavior was thermopositive and spontaneous. The maximum theoretical uptake
      computed by the Langmuir equation was 909.09 mg.g-1 at 303 K, which suggested
      that PAMH was an effective sorbent to eliminate anionic dye from aqueous
      solution.

PMID- 30107360
TI  - Model assessment of the prevailing fouling mechanisms in a submerged membrane
      anaerobic reactor treating low-strength wastewater.
AB  - Three models (blocking laws, combined and resistance-in-series) were applied to
      identify the prevailing fouling mechanisms in a submerged membrane in an up-flow
      anaerobic sludge blanket reactor treating municipal wastewater. Experimental runs
      were carried out at lab-scale with filtration periods of 4 and 10 min, followed
      by relaxation periods of one minute with and without nitrogen bubbling. In all
      conditions excepting one (IF4R), the blocking laws model showed a predominance of
      cake formation. With the combined model, cake formation coupled with
      intermediate, standard and complete fouling had the better fits in all
      conditions, excepting IF4 and IF4R. When sewage was fed, both models pointed at
      intermediate fouling in the absence of gas bubbling. The resistance-in-series
      model identified the positive effect of gas bubbling and a post-cake fouling
      behavior, not shown by the other two models. This modeling approach could be
      applied for achieving longer filtration runs in submerged UF membranes.

PMID- 30107361
TI  - Midtrimester transvaginal ultrasound cervical length screening for spontaneous
      preterm birth in diamniotic twin pregnancies according to chorionicity.
AB  - OBJECTIVE: To compare the mean transvaginal ultrasound (TVU) cervical length (CL)
      at midtrimester screening for spontaneous preterm birth in asymptomatic
      monochorionic diamniotic versus dichorionic diamniotic twin pregnancies STUDY
      DESIGN: This was a multicenter retrospective cohort study. Study subjects were
      identified at the time of a routine second trimester fetal ultrasound exam at 18
      0/7-23 6/7 weeks gestation. We excluded women that received progesterone,
      pessary, or cerclage. Distribution of CL was determined and normality was
      examined. Mean of TVU CL were compared between monochorionic diamniotic and
      dichorionic diamniotic pregnancies. The relationship of TVU CL with gestational
      age (GA) at delivery and incidence of spontaneous preterm birth (SPTB) at
      different TVU CL cut offs were assessed. Incidence of short TVU CL, defined as
      TVU CL <=30 mm, was also calculated in the two groups. RESULTS: 580 women with
      diamniotic twin pregnancies underwent TVU CL screening between 18 0/6 and 23 6/7
      weeks. 175 (30.2%) were monochorionic diamniotic pregnancies, and 405 (69.8%)
      were dichorionic pregnancies. The demographic characteristics were similar on
      both groups. The mean GA at TVU CL was about 20 week in both groups. The mean TVU
      CL was significantly lower in the monochorionic diamniotic (32.8 +/- 10.1)
      compared to the dichorionic (34.9 +/- 8.6) group (MD -2.10 mm, 95% CI -3.91 to 
      0.29). TVU CL <=30 mm was 16.6% (29/175) in the monochorionic group, and 11.9%
      (48/405) in the dichorionic group (aOR 1.48, 95% CI 1.03-2.43). Twins with a
      monochorionic diamniotic pregnancy had a significantly higher incidence of SPTB
      (53.1% vs 44.9%; aOR 1.22, 95% CI 1.22-1.79). For any given CL measured between
      18 0-7 and 23 6/7 weeks, gestational age at delivery for monochorionic diamniotic
      pregnancies was about 2 weeks earlier compared to dichorionic pregnancies (MD 
      2.1 weeks; ANCOVA P < 0.001). CONCLUSION: Monochorionic diamniotic twin
      pregnancies had a higher rate of spontaneous preterm birth than dichorionic
      diamniotic pregnancies. The higher rate of spontaneous preterm delivery in
      monochorionic pregnancies is associated with lower midtrimester TVU CL when
      compared to dichorionic pregnancies.

PMID- 30107362
TI  - Effects of opening the incubator on morphokinetics in mouse embryos.
AB  - OBJECTIVE: To evaluate the effects of incubator door openings by the sensitive
      measurement of morphokinetics using time-lapse imaging. STUDY DESIGN: To mimic
      lab practice and to evaluate minimal changes in culture conditions a randomized
      parallel group study with mouse embryos was designed. 249 murine zygotes derived
      from 31 mice were randomly distributed into two groups. Embryos of the control
      group were non-invasively monitored with a Primovision time-lapse system
      (Vitrolife) in the incubator that was completely closed for 5 days, while the
      conditions for the embryos in the treatment group were interrupted by two door
      openings per day of 10 s each. RESULTS: Door opening twice per day did not lead
      to significant differences in blastocyst formation rate (p = 0.820), however
      significantly more embryos hatched in a shorter duration (p = 0.011), and the
      embryos transitioned more quickly from 2C to 3C, from 3C to 4C, from 2C to 5C and
      from 5C to blastocyst stage (p < 0.001 in cc2, p = 0.037 in cc3, p = 0.002 in t2
      to t5, and p = 0.015 in t5 to blastocyst). Size of the blastocysts from the
      treatment group was 1.562 MUm smaller compared to that of control embryos (p =
      0.016). CONCLUSIONS: Even disruptions in culture conditions as simple as
      incubator door openings lead to measurable, significant changes in morphokinetics
      that would have been missed with standard parameters such as blastocyst rate.
      This underlines the relevance of undisturbed and stable culture conditions and
      emphasizes the need for further research in this field.

PMID- 30107363
TI  - Synthetic osmotic dilators in the induction of labour-An international
      multicentre observational study.
AB  - INTRODUCTION: To evaluate the effects of synthetic osmotic dilators (Dilapan-S/
      Dilasoft) in women who required induction of labour in a large prospective
      multicentre international observational study. MATERIALS AND METHODS: Primary
      outcomes were duration of Dilapan-S/Dilasoft insertion (hours), total induction -
      delivery interval (hours) and the rate of vaginal deliveries within 24 h (%).
      Secondary outcomes were the number of dilators inserted, Bishop score increase
      after extraction of Dilapan-S/Dilasoft, complications during induction (uterine
      contractions, uterine tachysystole and hyperstimulation, effect on the fetus) and
      post induction (infections and neonatal outcomes), agents / procedures used for
      subsequent induction of labour, immediate rate of spontaneous labours following
      cervical ripening period, rate of spontaneous vaginal deliveries, rate of
      instrumental vaginal deliveries and caesarean sections. RESULTS: Total of 543
      women were recruited across 11 study sites, of which, 444 women were eligible for
      analysis. With Dilapan-S/Dilasoft use of <12 h (n = 188) the overall vaginal
      delivery rate was 76.6% with 45.7% of these births occurring within 24 h, 66%
      within 36 h and 75.5% within 48 h from insertion of Dilapan-S/Dilasoft. The mean
      insertion-delivery interval for this group was 24.3(+/-10.4) hours. With Dilapan
      S/Dilasoft use of >12 h (n = 256), the overall vaginal delivery rate was 64.8%,
      with 16% of these births occurring within 24 h, 48.4% within 36 h and 54.7%
      within 48 h from insertion of Dilapan-S/Dilasoft. The mean insertion-delivery
      interval for this group was 39.1(+/-29.2) hours. The mean gain in the Bishops
      score was +3.6(+/-2.3). The mean number of Dilapan-S/Dilasoft dilators used was
      3.8 (+/-1.1). The overall rate of caesarean section was 30.1%. The overall
      complication rate was low including infection risk. No adverse neonatal outcome
      was attributable to the use of Dilapan-S/Dilasoft. CONCLUSION: Dilapan-S/Dilasoft
      are safe and effective methods for cervical ripening. Their use is associated
      with low maternal and neonatal complication rates. Future research should aim at
      level I clinical trials comparing Dilapan-S to other mechanical or
      pharmacological cervical ripening agents. CLINICAL TRIAL REGISTRATION:
      https://clinicaltrials.gov/ct2/show/NCT02318173.

PMID- 30107366
TI  - Forward trunk lean with arm support affects the activity of accessory respiratory
      muscles and thoracoabdominal movement in healthy individuals.
AB  - Despite the reported benefits of postures involving leaning the trunk forward
      with arm support for relieving dyspnea, how those postures influence the
      mechanics of breathing remains unclear. In response, the aim of the study
      reported here was to evaluate how posture (i.e., standing and sitting) and
      leaning the trunk forward with arm support affect the activity of accessory
      respiratory muscles and thoracoabdominal movement in healthy individuals. Thirty
      five volunteers (15 males and 20 females) aged 18-29 years breathed with the same
      rhythm in standing and sitting positions while upright and while leaning the
      trunk forward with arm support. Surface electromyography was performed to assess
      the activity of accessory inspiratory (i.e., during inspiration) and abdominal
      (i.e., during inspiration and expiration) muscles, and a motion capture system
      was used to assess thoracoabdominal movement. Results revealed that upper
      trapezius activity was significantly lower in forward-leaning postures than in
      upright ones (P = 005; etap2 = 0.311), although the activity of the
      sternocleidomastoideus and scalenus (P < 0.001; etap2 = 0.427-0.529), along with
      the anterior-to-posterior movement of the upper ribcage (P < 0.001; etap2 =
      0.546), were significantly greater in forward-leaning postures than in upright
      ones. The activity of the external oblique and transversus abdominis/internal
      oblique was significantly lower in sitting than in standing postures (P < 0.050;
      etap2 = 0.206-0.641), and though the activity of the transversus
      abdominis/internal oblique was significantly lower in forward-leaning than in
      upright postures (P <= 0.001; etap2 = 0.330-0.541), a significantly greater
      anterior-to-posterior movement of the abdomen was observed (P < 0.001; etap2 =
      0.662). However, the magnitude of the lower ribcage's medial-to-lateral movement
      was significantly lower in forward-leaning than in upright postures (P = 0.039;
      etap2 = 0.149). Leaning the trunk forward with arm support not only increased the
      use of accessory inspiratory muscles but also decreased the use of the
      transversus abdominis/internal oblique, which improved thoracoabdominal movement.

PMID- 30107367
TI  - Protective effect of ginsenoside metabolite compound K against diabetic
      nephropathy by inhibiting NLRP3 inflammasome activation and NF-kappaB/p38
      signaling pathway in high-fat diet/streptozotocin-induced diabetic mice.
AB  - Though the antidiabetic effect of ginsenoside compound K (CK) has been well
      studied, the effect of CK on diabetic nephropathy (DN) is not clear. Whether CK
      would have a protective effect against DN and it could exert the protective
      effect by inhibiting the oxidative stress, NLRP3 inflammasome and NF-kappaB/p38
      signaling pathway were investigated in this study. Here, the HFD (high fat
      diet)/STZ (streptozotocin)-induced DN mice model was established to assess the CK
      effect in vivo. Parallel experiments uncovering the molecular mechanism by which
      CK prevents from DN was performed in rat glomerular mesangial cell line HBZY-1
      exposed to high glucose. CK (10, 20, 40 mg/kg/day) were intragastrically
      administered for 8 weeks, the general status, biochemical parameters, renal
      pathological changes and oxidative stress-parameters were observed, and the NLRP3
      inflammasome and NF-kappaB/p38 signaling pathway were evaluated. The results
      showed that the elevated fasting blood glucose, serum creatinine, blood urea
      nitrogen and 24-hour urine protein of the DN mice were significantly decreased,
      and the proliferation of glomerular mesangial matrix was alleviated by CK. In
      addition, the generation of ROS in the kidney was significantly decreased, and
      the expression of Nox1 and Nox4 proteins were down-regulated. Further, the
      expression of NLRP3 inflammasome components (NLRP3, ASC and Caspase-1) and the
      inflammatory cytokines IL-1beta and IL-18 were also significantly down-regulated
      in vivo and in vitro. The phosphorylation of renal p38 MAPK was also inhibited by
      CK. MCC950 (an inhibitor of NLRP3 inflammasome) and VX-765 (a Caspase-1
      Inhibitor) showed significant interaction with CK on the decrease of IL-1beta
      concentration in HBZY-1 cells. In conclusion, our study provided evidence that
      the protective effect of CK on diabetes-induced renal injury is associated with
      down-regulating the expression of NADHP oxidase, and inhibition of ROS-mediated
      activation of NLRP3 inflammasome and NF-kappaB/p38 signaling pathway, suggesting
      its therapeutic implication for renal inflammation.

PMID- 30107365
TI  - Purple acid phosphatase inhibitors as leads for osteoporosis chemotherapeutics.
AB  - Purple acid phosphatases (PAPs) are metalloenzymes that catalyse the hydrolysis
      of phosphate esters under acidic conditions. Their active site contains a
      Fe(III)Fe(II) metal centre in mammals and a Fe(III)Zn(II) or Fe(III)Mn(II) metal
      centre in plants. In humans, elevated PAP levels in serum strongly correlate with
      the progression of osteoporosis and metabolic bone malignancies, which make PAP a
      target suitable for the development of chemotherapeutics to combat bone ailments.
      Due to difficulties in obtaining the human enzyme, the corresponding enzymes from
      red kidney bean and pig have been used previously to develop specific PAP
      inhibitors. Here, existing lead compounds were further elaborated to create a
      series of inhibitors with Ki values as low as ~30 MUM. The inhibition constants
      of these compounds were of comparable magnitude for pig and red kidney bean PAPs,
      indicating that relevant binding interactions are conserved. The crystal
      structure of red kidney bean PAP in complex with the most potent inhibitor in
      this series, compound 4f, was solved to 2.40 A resolution. This inhibitor
      coordinates directly to the binuclear metal centre in the active site as expected
      based on its competitive mode of inhibition. Docking simulations predict that
      this compound binds to human PAP in a similar mode. This study presents the first
      example of a PAP structure in complex with an inhibitor that is of relevance to
      the development of anti-osteoporotic chemotherapeutics.

PMID- 30107368
TI  - Erratum.

PMID- 30107369
TI  - Erratum.

PMID- 30107370
TI  - Erratum.

PMID- 30107371
TI  - Suckling Piglet Intestinal Enterocyte Nutrient Metabolism Changes.
AB  - BACKGROUND/AIMS: Intestinal morphology and the types of enterocytes are changed
      in piglets during the suckling period, but it is unclear whether these changes
      are associated with metabolic changes in epithelium. The present study was
      conducted to test the hypothesis that glucose, fatty acids, and amino acid
      metabolism in differentiated piglet enterocytes changed during suckling. METHODS:
      Twenty-four piglets (Duroc * [Landrace * Yorkshire]) from 8 litters (3
      piglets/litter) were selected. A single piglet from each litter was randomly
      selected and euthanized at days 7, 14, and 21. Differentiated enterocytes (DE)
      were isolated from their mid-jejunum. Isobaric tags for relative and absolute
      quantification and subsequent liquid chromatography-tandem mass spectrometry were
      used to identify and measure protein synthesis. RESULTS: The results showed that
      various activities, including: cellular processes; metabolic processes;
      biological regulation; pigmentation; and, localization, in DEs changed during
      suckling. Metabolic process analyses revealed that protein expression related to
      glycolysis and citrate cycle was decreased from day 7 to day 14. The number of
      differentiated enterocytes of 21 d piglets increased compared to 7 d piglets.
      Most of the proteins involved in fatty acid and amino acids metabolism had
      decreased DE expression between day 7 and day 14. Some, but not all, detected
      proteins down-regulated in DEs of 21 day piglets compared to 7 day piglets.
      CONCLUSION: These results indicate that glucose, fatty acids, and amino acids
      metabolism changed during suckling. This may provide useful information for
      designing feed formulas and regulating piglet intestinal growth and development.

PMID- 30107373
TI  - Erratum.

PMID- 30107372
TI  - Clinical Impact of Post-Progression Survival on Overall Survival in Elderly
      Patients with Non-Small-Cell Lung Cancer Harboring Sensitive EGFR Mutations
      Treated with First-Line EGFR Tyrosine Kinase Inhibitors.
AB  - BACKGROUND/AIMS: More than 50% of patients with lung cancer are aged > 65 years,
      and non-small-cell lung cancer (NSCLC) accounts for 85% of all cases of lung
      cancer among both elderly and adult patients. Subsequent therapies confound the
      capability to discern the effect of first-line chemotherapy on overall survival
      (OS). Therefore, using individual-level data, our study aimed to determine the
      relationships of progression-free survival (PFS) and post-progression survival
      (PPS) with OS after first-line epidermal growth factor receptor-tyrosine kinase
      inhibitor (EGFR-TKI) treatment in elderly patients with NSCLC harboring sensitive
      EGFR mutations. METHODS: Between April 2008 and December 2015, we analyzed 68
      elderly patients with NSCLC harboring sensitive EGFR mutations and treated with
      first-line EGFR-TKI. The relationships of PFS and PPS with OS were analyzed at an
      individual level. RESULTS: Linear regression analysis showed that PPS was more
      closely associated with OS (R2 = 0.54) than PFS was (R2 = 0.48). Best response at
      first-line treatment, performance status at the end of first-line treatment, and
      administration of EGFR-TKI rechallenge were significantly correlated with PPS.
      CONCLUSIONS: PPS has a stronger impact on OS than PFS does in elderly patients
      with NSCLC harboring sensitive EGFR mutations and treated with first-line EGFR
      TKI. These results indicate that OS in this patient population may be influenced
      by treatments subsequent to first-line chemotherapy; however, this remains to be
      verified in prospective studies.

PMID- 30107374
TI  - Streptococcus mutans and Streptococcus sanguinis Expression of Competition
      Related Genes, Under Sucrose.
AB  - Streptococcus mutans synthesizes 3 glucosyltransferases (Gtfs) associated with
      cariogenic biofilms, while commensal Streptococcus sanguinis produces only one;
      gtfP and hydrogen peroxide (H2O2) by SpxB. The aim was to test the hypothesis
      that under a sucrose-induced cariogenic challenge, the expression of competition
      related genes is differentially regulated depending on whether S. sanguinis or S.
      mutans primarily colonize enamel. Dual-species biofilms of S. sanguinis and S.
      mutans were formed under different colonization sequences on enamel slabs and
      exposed to 10% sucrose for 5 min, 3*/day for 5 days. Biofilms were analyzed for
      the transcriptional response of competition-related genes encoding gtfB, gtfC,
      and gtfD for S. mutans and gtfP and spxB for S. sanguinis. In addition,
      acidogenicity (pH) and viable cells in each of the conditions were determined.
      For all the genes, a downregulation was observed during simultaneous colonization
      by both bacterial species. In contrast, gtfB was upregulated when S. sanguinis
      was the first colonizer (p < 0.05). Both gtfC and gtfD were upregulated during
      sequential inoculation with S. sanguinis as the first colonizer. An eleven-fold
      upregulation of gtfP was observed in biofilms with S. mutans as initial colonizer
      (p < 0.05), with a moderate increase in spxB expression. The lowest pH values and
      viable cells of S. sanguinis were observed when S. mutans first colonized the
      enamel slabs, compared to the other conditions (p < 0.05). Demanding sucrose
      challenged oral environment requires increased expression of virulence traits to
      effectively compete and thrive in the dental biofilm, especially when the
      competitor has already colonized the ecological niche.

PMID- 30107375
TI  - A Membrane-Targeted Peptide Inhibiting PtxA of Phosphotransferase System Blocks
      Streptococcus mutans.
AB  - Streptococcus mutans, the primary cause of dental caries, takes up carbohydrates
      through the phosphoenolpyruvate sugar phosphotransferase system (PTS). This study
      aimed to identify a novel membrane-targeted antimicrobial peptide (AMP) that
      could also target the L-ascorbate-specific PtxA component of the S. mutans PTS
      system. C10-KKWW was identified and selected using virtual screening of a
      lipopeptide library, a minimum inhibiting concentration (MIC) assay, cytotoxicity
      assays and a hemolysis assay. Surface plasmon resonance confirmed that C10-KKWW
      had a high binding affinity for PtxA. Combining with scanning electron microscopy
      and cell permeability assay, it was shown that the effects of C10-KKWW could be
      attributed to both membrane and PtxA. Wild type (WT) S. mutans, a ptxA deletion
      mutant (DeltaptxA), and a mutant-complemented strain (CptxA), were cultured
      consistently in brain heart infusion (BHI) medium, tryptone-vitamin medium
      supplemented with 15 mM L-ascorbate (TVL), or for 5 h in BHI supplemented with
      7.4 mM sodium L-ascorbate. Compared to ?ptxA, in WT S. mutans and CptxA, C10-KKWW
      had a stronger MIC (3.9 MUg/mL), and distinctively decreased biofilm viability.
      The extracellular concentrations of L-ascorbate/sodium L-ascorbate were not
      changed before and after WT treated with C10-KKWW. L-ascorbate-induced operon
      genes, or other PTS genes, were significantly suppressed by C10-KKWW. In
      conclusion, C10-KKWW has been developed; it acts through interaction with the
      bacterial membrane and interferes with L-ascorbate translocation to inhibit S.
      mutans growth and eradicate its biofilm. C10-KKWW may be especially effective at
      optimal oral ascorbate levels. A combination of C10-KKWW with sodium L-ascorbate
      might also be a novel strategy for dental caries treatment.

PMID- 30107376
TI  - Early Histological Changes in Post-Transplant Encapsulating Peritoneal Sclerosis.

PMID- 30107377
TI  - Minimally Invasive Intervention for Primary Caries Lesions: Are Dentists
      Implementing This Concept?
AB  - Contemporary minimally invasive treatment concepts for restorative treatment of
      primary caries lesions include both delayed intervention and smaller-sized
      preparations restricted to removal of carious tissue. The aim of this study was
      to investigate whether these concepts have resulted in a trend towards a more
      conservative choice made by dentists regarding treatment thresholds and
      restorative techniques. The results from previously conducted, precoded
      questionnaires developed by Espelid and Tveit, as well as from a recent Dutch
      questionnaire, were collected and analysed. A worldwide trend towards more
      minimally invasive strategies in the operative treatment of caries lesions could
      not be observed, neither for the initiation of operative treatment nor for the
      preparation techniques. However, in some countries, changes over time could be
      assessed, especially in Norway, where a reduction in the proportion of
      interventions is visible for both occlusal and approximal lesions, indicating
      that more dentists are postponing interventions until the lesions have progressed
      to a deeper level. From the Dutch national survey, it could be concluded that
      operators that intervene at an earlier stage of approximal lesioning (stage <=4)
      also intervene at an earlier stage of occlusal caries (stage <=3) (p = 0.012; OR
      = 2.52; 95% CI: 1.22-5.22). Generally, it can be concluded that dentists
      worldwide still tend to operatively intervene at a too early stage of caries,
      although variations exist between countries. A worldwide shift could be observed
      in the restorative material applied, since composite resin has almost completely
      replaced amalgam for restoring primary caries lesions.

PMID- 30107379
TI  - Erratum.

PMID- 30107378
TI  - Nontumorous Portal Vein Thrombosis in Liver Cirrhosis: Possible Role of beta
      Blockers.
AB  - OBJECTIVE: Nonselective beta-blockers (NSBB) are used in liver cirrhosis (LC) to
      prevent variceal bleeding because they decrease portal pressure. A main risk
      factor for the development of portal vein thrombosis (PVT) in LC is decreased
      portal vein inflow velocity. The aim of our study was to examine retrospectively
      the incidence of PVT and its correlation with the use of beta-blockers in a
      cohort of LC patients. SUBJECTS AND METHODS: Data from 230 LC patients (90% Child
      Pugh class A), who had been followed up for at least 5 years, were reviewed. The
      diagnosis of PVT was made by ultrasound. The presence of PVT was evaluated with
      multiple logistic regression analysis where the independent variables were those
      significant in the univariate analysis. RESULTS: The prevalence of PVT at
      baseline was 4.5%, and the incidence was 4.3% at 5 years; among the subjects
      taking beta blockers, 46.4% were taking NSBB. A total of 19 PVT cases were found.
      Grade of esophageal varices (p < 0.01), PLT (p < 0.003), INR (p < 0.03), spleen
      diameter (p < 0.001) and PLT/spleen ratio (p < 0.0005) were significantly
      associated with PVT. The use of NSBB indicated a higher risk of PVT compared to
      selective beta-blockers (SBB) (p < 0.05). In logistic regression analysis only
      the grade of esophageal varices was significant (p < 0.02). Univariate analysis
      of patients taking beta-blockers showed an association of PVT with grade of
      esophageal varices (p < 0.01), CP class (p < 0.02), AST (p < 0.03), ALT and
      albumin (p < 0.02), PLT count and PLT/LD (p < 0.03), longitudinal diameter of the
      spleen (p < 0.005), ascites (p < 0.05), portal vein (p < 0.0001) and NSBB (OR
      8.1; 95% CI 1.7-38.8). CONCLUSION: NSBB seem to play a role in PV thrombogenesis.
      Further studies are needed, especially in decompensated LC patients.

PMID- 30107381
TI  - Cytokine Clearances in Critically Ill Patients on Continuous Renal Replacement
      Therapy.
AB  - BACKGROUND/AIMS: We sought to quantify any differences in cytokine clearance
      between continuous venovenous hemofiltration (CVVH-convective) compared to
      continuous venovenous hemodialysis (CVVHD-diffusive). METHODS: We conducted a 20
      patient, multicenter, prospective, open-label randomized trial (CVVH or CVVHD) at
      continuous renal -replacement therapy (CRRT) initiation. Blood, urine, and
      effluent were collected at 0, 4, 24, and 48 h after initiation of CRRT. Serum
      electrolytes, cytokines levels, and clearances were measured. Cytokines studies
      included IL-1beta, IL-1RA, IL-6, IL-10, and TNFalpha. RESULTS: We randomized 20
      patients to receive CRRT. After 4 h of CRRT there was no difference in total
      cytokine levels or change in cytokine concentrations across the 2 groups. With
      the exception of IL-1 RA, all cytokines levels decreased across patient groups
      regardless of modality. There was no significant difference in cytokine
      concentration across CRRT modality for any time point. CONCLUSION: Within the
      first 4 h of CRRT initiation, there is no significant difference between cytokine
      or solute clearance between CVVH and CVVHD.

PMID- 30107382
TI  - Erratum.

PMID- 30107380
TI  - Isolation and Characterization of a Chinese Hamster Ovary Heparan Sulfate Cell
      Mutant Defective in Both Met Receptor Binding and Hepatocyte Growth Factor
      NK1/Met Signaling.
AB  - BACKGROUND/AIMS: The up-regulation of hepatocyte growth factor/receptor, HGF/Met,
      signal transduction is observed in most of human cancers. Specific heparan
      sulfate structures enhance the HGF/Met signaling at both cell and animal-based
      model systems. Biochemical studies indicate that heparan sulfate interacts with
      HGF and a natural occurring splicing variant NK1 of HGF with similar affinity.
      However, it is currently unknown if cell surface heparan sulfate binds to Met at
      physiological conditions and if specific cell surface heparan sulfate structures
      are required for effective HGF/Met or NK1/Met signaling. METHODS: An established
      flow sorting strategy was used to isolate a soluble Met recombinant protein
      binding positive or negative CHO cell clones different only in specific heparan
      sulfate structures. The cell surface bindings were imaged by confocal microscopy
      and flow cytometry analysis. Glucosamine vs. galactosamine contents from media-,
      cell surface-, and cell association glycosaminoglycans were quantified by HPLC.
      35S-sulfate labeled glycosaminoglycans were characterized by anion exchange and
      size-exclusion HPLC. Heparan sulfate disaccharide compositions were determined by
      HPLC-MS analysis. Western blot analyses of MAPK-p42/44 were used to monitor HGF-
      and NK1-facillated Met signaling. RESULTS: CHO-Positive but not CHO-Negative cell
      surface heparan sulfate bound to Met recombinant protein and HGF/NK1 further
      promoted the binding. Overall glycosaminoglycan analysis results indicated that
      the CHO-Negative cells had reduced amount of heparan sulfate, shorter chain
      length, and less 6-O-sulfated disaccharides compared to that of CHO-Positive
      cells. Moreover, CHO-Negative cells were defective in NK1/Met but not HGF/Met
      signaling. CONCLUSIONS: This study demonstrated that soluble Met recombinant
      protein bound to cell surface HS at physiological conditions and a Met /HGF or
      NK1/HS ternary signaling complex might be involved in Met signaling. Shorter HS
      chains and reduced 6-O-sulfation might be responsible for reduced Met binding and
      the diminished NK1-initiated signaling in the CHO-Negative cells. The unique CHO
      Positive and CHO-Negative cell clones established in current study should be
      effective tools for studying the role of specific glycosaminoglycan structures in
      regulating Met signaling. Such knowledge should be useful in developing
      glycosaminoglycan-based compounds that target HGF/Met signaling.

PMID- 30107383
TI  - Pulsatility Index as a Novel Parameter for Perfusion in Mouse Model of Hindlimb
      Ischemia.
AB  - BACKGROUND/AIMS: In clinical settings, the pulsatility index (PI) has become a
      widely used tool for monitoring obstetrics or other vascular diseases. It is
      based on the maximum Doppler shift waveform derived from ultrasonography.
      However, it remains unclear whether the PI levels are correctly predicted from
      the perfusion in mouse model of hindlimb ischemia. METHODS: To explore the
      relationship between PI and perfusion, we generated a unilateral hindlimb
      ischemia model in 8-week-old C57BL/6 male mice by ligation of the right common
      iliac artery and femoral artery. These mice were monitored with laser Doppler
      perfusion imaging (LDPI) and an ultrasound system (Vevo2100). Vessel densities in
      ischemic skeletal muscles were measured with vWF staining, which functions as a
      marker for endothelial cells. In order to further verify PI evaluation in other
      conditions, we performed therapeutic experiments using hindlimb ischemic mouse
      with PBS or FGF2 treatment. RESULTS: In the mouse model of hindlimb ischemia, the
      PI levels were continuously elevated and were accompanied by an increased ratio
      of perfusion to blood flow. 1 and 4 weeks after ischemia, the densities of vWF
      staining were correlated with PI values. Moreover, the PI index exactly reflected
      the perfusion in hindlimb ischemic mice after FGF2 treatment, while it indicated
      the condition of angiogenesis after therapeutic treatment based on the
      association between PI values and the number of vWF-positive stained cells in
      muscles. CONCLUSION: This study confirms the utility of a noninvasive and
      reproducible ultrasound index for a rapid evaluation of perfusion and blood
      recovery after hindlimb ischemia in vivo. PI, as one stable and comparable
      parameter, is correlated with angiogenesis in hindlimb ischemic mouse. Moreover,
      PI can exactly reflect perfusion and angiogenesis in therapeutic hindlimb
      ischemic mouse models. This study suggested that PI can serve as a novel index
      for relatively reproducible and repeatable blood flow recovery in the evaluation
      of emerging ischemic therapies and disease development in mouse models of
      hindlimb ischemia.

PMID- 30107385
TI  - Erratum.

PMID- 30107386
TI  - Martin Method for Estimation of Low-Density Lipoprotein Cholesterol.

PMID- 30107384
TI  - Constitutive Activation of beta-Catenin in Differentiated Osteoclasts Induces
      Bone Loss in Mice.
AB  - BACKGROUND/AIMS: Activation of the Wnt/beta-catenin signalling pathway has been
      widely investigated in bone biology and shown to promote bone formation. However,
      its specific effects on osteoclast differentiation have not been fully
      elucidated. Our study aimed to identify the role of beta-catenin in
      osteoclastogenesis and bone homeostasis. METHODS: In the present study, exon 3 in
      the beta-catenin gene (Ctnnb1) allele encoding phosphorylation target
      serine/threonine residues was flanked by floxP sequences. We generated mice
      exhibiting conditional beta-catenin activation (Ctsk-Cre;Ctnnb1flox(exon3)/+,
      designated CA-beta-catenin) by crossing Ctnnb1flox(exon3)/flox(exon3) mice with
      osteoclast-specific Ctsk-Cre mice. Bone growth and bone mass were analysed by
      micro-computed tomography (micro-CT) and histomorphometry. To further examine
      osteoclast activity, osteoclasts were induced from bone marrow monocytes (BMMs)
      isolated from CA-beta-catenin and Control mice in vitro. Osteoclast
      differentiation was detected by tartrate-resistant acid phosphatase (TRAP)
      staining, immunofluorescence staining and reverse transcription-quantitative PCR
      (RT-qPCR) analysis. RESULTS: Growth retardation and low bone mass were observed
      in CA-beta-catenin mice. Compared to controls, CA-beta-catenin mice had
      significantly reduced trabecular bone numbers under growth plates as well as
      thinner cortical bones. Moreover, increased TRAP-positive osteoclasts were
      observed on the surfaces of trabecular bones and cortical bones in the CA-beta
      catenin mice; consistent results were observed in vitro. In the CA-beta-catenin
      group, excessive numbers of osteoclasts were induced from BMMs, accompanied by
      the increased expression of osteoclast-associated marker genes. CONCLUSION: These
      results indicated that the constitutive activation of beta-catenin in osteoclasts
      promotes osteoclast formation, resulting in bone loss.

PMID- 30107387
TI  - Superior-Based Transposition Flap: A Novel Technique in Rhinoplasty.
AB  - Background: The cephalic trimming of the lower lateral cartilage (LLC) is an
      attempt to reduce tip bulbosity; unfortunately, it has the potential to cause a
      pinched nose deformity and valve collapse. Objectives: To use the superior-based
      transposition (ST) flap to reshape, relocalize, and reinforce the LLC as a
      support material for both internal and external valves with aesthetic
      corrections, leaving the scroll area untouched. Methods: A total of 367 patients
      (female, 215; male, 152) were operated with the presented technique. The ST flap
      is simply used to prepare a cartilage flap based on the scroll area in the
      cephalic portion of the LLC, and then, this flap is advanced over the remaining
      LLC. The data were evaluated retrospectively. Results: Functionally, the ST flap
      was used to reshape and support the LLC and the internal valve by keeping the
      scroll intact and increasing the internal valve angle. The support and suspension
      of the LLC with this novel technique improve the functional results and prevent
      complications such as stenosis of both the external and internal valve angles.
      Aesthetically, the convexity and concavity of the LLC could be fixed with the
      adaptation of these two surfaces in different angles, thereby achieving a
      narrower, refined, and aesthetically pleasing tip. Conclusions: This study
      demonstrates that the ST flap can be one of the main maneuvers performed during
      rhinoplasty for many purposes, such as reshaping and supporting the LLC,
      increasing the tip rotation, achieving more aesthetically pleasing tips,
      suspending the internal and external valves, and protecting the scroll area.

PMID- 30107388
TI  - Functional diversity and convergence in the evolution of plant reproductive
      structures.
AB  - Background and Aims: Structures that simultaneously perform many functional roles
      are likely to show a variety of morphological solutions to these demands, and
      thus probably exhibit high morphological disparity. In contrast, specialization
      for a few simple functions should result in a more limited suite of morphologies.
      We explore this idea using lycopsid reproductive structures, which, throughout
      their history, have performed a limited set of functional roles compared with the
      reproductive structures of other plant groups such as seed plants. Methods: We
      scored living and fossil lycopsid taxa for 18 discrete character measurements and
      several continuous traits, including sporangium size, supporting axis diameter,
      and strobilus length and width. We used the discrete characters to construct a
      multivariate morphospace for lycopsid reproductive morphology through time, and
      the continuous characters to test whether fossil and extant lycopsids show
      similar patterns of tissue allocation within reproductive structures. Results:
      Lycopsids occupy similar areas of reproductive morphospace and show similar
      patterns of tissue allocation over most of their history, alternating between
      diffuse fertile zones with leaf-like sporophylls and compact strobili with
      specialized sporophylls that allow sporangia to be closely packed while also
      protected during their development. Growth habit also plays an important role in
      lycopsid reproductive evolution, broadly influencing the size and shape of
      reproductive structures. Conclusions: Lycopsid reproductive structures are
      primarily specialized for densely packaging sporangia, and are consistent with
      the idea that performing limited functional roles is associated with reduced
      morphological disparity. Morphologies similar to lycopsid strobili are also found
      in other groups with simple, wind-dispersed propagules, suggesting that the same
      processes occur across plant lineages.

PMID- 30107390
TI  - A PrEP model incorporating clinical pharmacist encounters and antimicrobial
      stewardship program oversight may improve retention in care.

PMID- 30107389
TI  - Unmasking cryptic biodiversity in polyploids: origin and diversification of Aster
      amellus aggregate.
AB  - Background and Aims: The origin of different cytotypes by autopolyploidy may be
      an important mechanism in plant diversification. Although cryptic autopolyploids
      probably comprise the largest fraction of overlooked plant diversity, our
      knowledge of their origin and evolution is still rather limited. Here we study
      the presumed autopolyploid aggregate of Aster amellus, which encompasses diploid
      and hexaploid cytotypes. Although the cytotypes of A. amellus are not
      morphologically distinguishable, previous studies showed spatial segregation and
      limited gene flow between them, which could result in different evolutionary
      trajectories for each cytotype. Methods: We combine macroevolutionary,
      microevolutionary and niche modelling tools to disentangle the origin and the
      demographic history of the cytotypes, using chloroplast and nuclear markers in a
      dense population sampling in central Europe. Key Results: Our results revealed a
      segregation between diploid and hexaploid cytotypes in the nuclear genome, where
      each cytotype represents a monophyletic lineage probably homogenized by concerted
      evolution. In contrast, the chloroplast genome showed intermixed connections
      between the cytotypes, which may correspond to shared ancestral relationships.
      Phylogeny, demographic analyses and ecological niche modelling supported an
      ongoing differentiation of the cytotypes, where the hexaploid cytotype is
      experiencing a demographic expansion and niche differentiation with respect to
      its diploid relative. Conclusions: The two cytotypes may be considered as two
      different lineages at the onset of their evolutionary diversification.
      Polyploidization led to the occurrence of hexaploids, which expanded and changed
      their ecological niche.

PMID- 30107391
TI  - Y-27632 Preconditioning Enhances Transplantation of Human Induced Pluripotent
      Stem Cell-Derived Cardiomyocytes in Myocardial Infarction Mice.
AB  - Introduction: The effectiveness of cell-based treatments for regenerative
      myocardial therapy is limited by low rates of cell engraftment. Y-27632 inhibits
      Rho kinase (ROCK), which regulates the cytoskeletal changes associated with cell
      adhesion, and has been used to protect cultured cells during their passaging.
      Here, we investigated whether preconditioning of cardiomyocytes, derived from
      human induced-pluripotent stem cells (hiPSC-CM), with Y-27632 improves their
      survival and engraftment in a murine model of acute myocardial infarction (MI).
      Methods and results: After MI induction, mice were subjected to intramyocardial
      injections of PBS, hiPSC-CM cultured under standard conditions (hiPSC-CM-RI), or
      Y-27632-preconditioned hiPSC-CM (hiPSC-CM+RI). The resulting engraftment rate
      calculated 4 weeks after implantation was significantly higher and the abundance
      of apoptotic transplanted cells was significantly lower in hiPSC-CM+RI recipients
      than in hiPSC-CM-RI animals. In cultured hiPSC-CM, Y-27632-preconditioning
      reversibly reduced contractile activity and the expression of troponin genes,
      while increasing their attachment to an underlying mouse cardiomyocyte (HL1)
      monolayer. Y-27632-preconditioning also increased the expression of N-cadherin
      and integrin beta1, the two cell junction proteins. hiPSC-CM+RI were also larger
      in cell area with greater cytoskeletal alignment and a more rod-like shape than
      hiPSC-CM-RI, both after transplantation (in vivo) and in culture. The effects of
      Y-27632 preconditioning on contractile activity and morphology of hiPSC-CMs in
      culture, as well as on their engraftment rate and apoptotic death in MI mouse
      grafts, could be recapitulated by hiPSC-CM treatment with the L-type calcium
      channel blocker verapamil. Conclusion: Preconditioning with the ROCK inhibitor Y
      27632 increased the engraftment of transplanted hiPSC-CM in a murine MI model,
      while reversibly impairing hiPSC-CM contractility and promoting adhesion.

PMID- 30107392
TI  - Neurological, cognitive, and psychological findings among survivors of Ebola
      virus disease from the 1995 Ebola outbreak in Kikwit, Democratic Republic of
      Congo: a cross-sectional study.
AB  - Background: Clinical sequelae of Ebola virus disease (EVD) have not been
      described more than three years post-outbreak. We examined survivors and close
      contacts from the 1995 Ebola outbreak in Kikwit, Democratic Republic of Congo
      (DRC), and determined prevalence of abnormal neurological, cognitive, and
      psychological findings and their association with EVD survivorship. Methods: From
      August to September 2017, we conducted a cross-sectional study in Kikwit, DRC.
      Over two decades after the EVD outbreak, we recruited EVD survivors and close
      contacts from the outbreak to undergo physical examination and culturally adapted
      versions of the Folstein mini-mental status exam (MMSE) and Goldberg Anxiety and
      Depression Scale (GADS). We estimated the strength of relationships between EVD
      survivorship and health outcomes using linear regression models by comparing
      survivors vs. close contacts, adjusting for age, sex, educational level, marital
      status and healthcare worker status. Results: We enrolled 20 EVD survivors and
      187 close contacts. Among the 20 EVD survivors, 4 (20%) reported at least one
      abnormal neurological symptom and 3 (15%) had an abnormal neurological
      examination. Among the 187 close contacts, 14 (11%) reported at least one
      abnormal neurologic symptom and 9 (5%) had an abnormal neurological examination.
      EVD survivors had lower mean MMSE and higher mean GADS scores as compared to
      close contacts (MMSE: adjusted coefficient: -1.85; 95% CI: -3.63, -0.07; GADS:
      adjusted coefficient: 3.91; 95% CI: 1.76, 6.04). Conclusions: EVD survivors can
      have lower cognitive scores and more symptoms of depression and anxiety than
      close contacts more than two decades after Ebola virus outbreaks.

PMID- 30107393
TI  - Stability of Isocyanates Sampled in Fire Smokes.
AB  - Inhalation of airborne isocyanates is associated with acute asthma attacks and
      inflammation in the respiratory tract as well as cancer. These highly reactive
      compounds are used as monomers in various applications such as foams for
      insulation materials and upholstery furniture and are therefore commonly found in
      fire smoke from insulation materials, such as rigid polyisocyanurate (PIR) foams.
      Consequently, there is an increasing concern regarding the potential adverse
      health effects they may cause during this type of exposure.The aim of this study
      was to investigate the stability of generated isocyanates from aerobic pyrolysis
      of PIR after sampling in the derivatization solution as well as after sample
      preparation to establish the optimal storage conditions and rate of degradation.
      Both airborne and particle-bound isocyanates were collected, using dibutylamine
      as derivatization agent in a midget impinger and impregnated filter after the
      impinger. The rapid degradation of the generated isocyanates after sampling
      emphasizes the need for a prompt sample preparation and analysis, in particular
      for the collected mono-isocyanates, as the concentration decreased by 50% within
      4-8 h.

PMID- 30107394
TI  - A dramatic acute respiratory distress and refractory cardiac arrest related to
      complete aortic valve embolization.

PMID- 30107395
TI  - Major progress in anticoagulant uptake for atrial fibrillation at last: does it
      translate into stroke prevention?

PMID- 30107396
TI  - Intraspecific variation in soy across the leaf economics spectrum.
AB  - Background and Aims: Intraspecific trait variation (ITV) is an important
      dimension of plant ecological diversity, particularly in agroecosystems, where
      phenotypic ITV (within crop genotypes) is an important correlate of key
      agroecosystem processes including yield. There are few studies that have
      evaluated whether plants of the same genotype vary along well-defined axes of
      biological variation, such as the leaf economics spectrum (LES). There is even
      less information disentangling environmental and ontogenetic determinants of crop
      ITV along an intraspecific LES, and whether or not a plant's position along an
      intraspecific LES is correlated with reproductive output. Methods: We sought to
      capture the extent of phenotypic ITV within a single cultivar of soy (Glycine
      max) - the world's most commonly cultivated legume - using a data set of nine
      leaf traits measured on 402 leaves, sampled from 134 plants in both agroforestry
      and monoculture management systems, across three distinct whole-plant ontogenetic
      stages (while holding leaf age and canopy position stable). Key Results: Leaf
      traits covaried strongly along an intraspecific LES, in patterns that were
      largely statistically indistinguishable from the 'universal LES' observed across
      non-domesticated plants. Whole-plant ontogenetic stage explained the highest
      proportion of phenotypic ITV in LES traits, with plants progressively expressing
      more 'resource-conservative' LES syndromes throughout development. Within
      ontogenetic stages, leaf traits differed systematically across management
      systems, with plants growing in monoculture expressing more 'resource
      conservative' trait syndromes: trends largely owing to an approximately >=50%
      increases in leaf mass per area (LMA) in high-light monoculture vs. shaded
      agroforestry systems. Certain traits, particularly LMA, leaf area and maximum
      photosynthetic rates, correlated closely with plant-level reproductive output.
      Conclusions: Phenotypic ITV in soy is governed by constraints in trait trade-offs
      along an intraspecific LES, which in turn (1) underpins plant responses to
      managed environmental gradients, and (2) reflects shifts in plant functional
      biology and resource allocation that occur throughout whole-plant ontogeny.

PMID- 30107397
TI  - Drebrin: a new player in angiotensin II-induced aortopathies.

PMID- 30107398
TI  - Deep Sequencing of Fosmid Clones Indicates Gene Conversion in the Male-Specific
      Region of the Giant Panda Y Chromosome.
AB  - The giant panda (Ailuropoda melanoleuca) is popular around the world and is
      widely recognized as a symbol of nature conservation. A draft genome of the giant
      panda is now available, but its Y chromosome has not been sequenced. Y chromosome
      data are necessary for study of sex chromosome evolution, male development, and
      spermatogenesis. Thus, in the present study, we sequenced two parts of the giant
      panda Y chromosome utilizing a male giant panda fosmid library. The sequencing
      data were assembled into two contigs, each ~100 kb in length with no gaps,
      providing high-quality resources for studying the giant panda Y chromosome.
      Annotation and transposable element comparison indicates varied evolutionary
      pressure in different regions of the Y chromosome. Two genes, zinc finger
      protein, Y-linked (ZFY) and lysine demethylase 5D (KDM5D), were annotated and
      gene conversion was observed for ZFY exon 7. Phylogenetic analysis also revealed
      that this gene conversion event happened independently in multiple mammalian
      lineages, indicating a putative mechanism to maintain the function of this
      particular gene on the Y chromosome. Furthermore, a transposition event,
      discovered through comparative alignment with the giant panda X chromosome
      sequence, may be involved in the process of gaining new genes on the Y
      chromosome. Thus, these newly obtained Y chromosome sequences provide valuable
      insights into the genomic patterns of the giant panda.

PMID- 30107399
TI  - Monitoring changes in the Gene Ontology and their impact on genomic data
      analysis.
AB  - Background: The Gene Ontology (GO) is one of the most widely used resources in
      molecular and cellular biology, largely through the use of "enrichment analysis."
      To facilitate informed use of GO, we present GOtrack
      (https://gotrack.msl.ubc.ca), which provides access to historical records and
      trends in the GO and GO annotations. Findings: GOtrack gives users access to gene
      and term-level information on annotations for nine model organisms as well as an
      interactive tool that measures the stability of enrichment results over time for
      user-provided "hit lists" of genes. To document the effects of GO evolution on
      enrichment, we analyzed more than 2,500 published hit lists of human genes (most
      older than 9 years ); 53% of hit lists were considered to yield significantly
      stable enrichment results. Conclusions: Because stability is far from assured for
      any individual hit list, GOtrack can lead to more informed and cautious
      application of GO to genomics research.

PMID- 30107402
TI  - Traumatic oesophageal perforation: a successful management based on the
      Pittsburgh Perforation Severity Score.
AB  - Oesophageal perforation is a severe life-threatening clinical condition with high
      mortality and morbidity needing rapid interdisciplinary approach to be
      effectively managed. Recently, on the basis of multicentric retrospective data,
      we proposed a decision tree for the treatment of oesophageal perforations based
      on the Pittsburgh Perforation Severity Score (PSS). We now report the first case
      of a traumatic oesophageal perforation, which was successfully treated according
      to the application of the PSS decision tree.

PMID- 30107401
TI  - Methicillin-resistant Staphylococcus aureus Colonization and Pre- and Post
      hospital Discharge Infection Risk.
AB  - Background: The Department of Veterans Affairs implemented an active surveillance
      program for methicillin-resistant Staphylococcus aureus (MRSA) in 2007 in which
      acute care inpatients are tested for MRSA carriage on admission, unit-to-unit
      transfer, and discharge. Using these data, we followed patients longitudinally to
      estimate the difference in infection rates for those who were not colonized,
      those who were colonized on admission (importers), and those who acquired MRSA
      during their stay. We examined MRSA infections that occurred prior to discharge
      and at 30, 90, 180, and 365 days after discharge. Methods: We constructed a
      dataset of 985626 first admissions from January 2008 through December 2015 who
      had surveillance tests performed for MRSA carriage. We performed multivariable
      Cox proportional hazards and logistic regression models to examine the
      relationship between MRSA colonization status and infection. Results: The MRSA
      infection rate across the predischarge and 180-day postdischarge time period was
      5.5% in importers and 7.0% in acquirers without a direct admission to the
      intensive care unit (ICU) and 11.4% in importers and 11.7% in acquirers who were
      admitted directly to the ICU. The predischarge hazard ratio for MRSA infection
      was 29.6 (95% confidence interval [CI], 26.5-32.9) for importers and 28.8 (95%
      CI, 23.5-35.3) for acquirers compared to those not colonized. Fully 63.9% of all
      MRSA pre- and postdischarge infections among importers and 61.2% among acquirers
      occurred within 180 days after discharge. Conclusions: MRSA colonization
      significantly increases the risk of subsequent MRSA infection. In addition, a
      substantial proportion of MRSA infections occur after discharge from the
      hospital.

PMID- 30107403
TI  - Technical challenges of lung transplantation in children after arterial switch
      operation.
AB  - Pulmonary arterial hypertension after arterial switch operation for transposition
      of the great arteries is rare. Lung transplantation can be the last option in
      cases of failed medical therapy. We report 2 paediatric patients who underwent
      lung transplantation for this indication. Altered hilar anatomy, mediastinal
      adhesions and haemostatic control represent the main technical challenges. Volume
      reduction surgery is sometimes necessary to address altered cardiopulmonary
      relationships while expanding the donor pool.

PMID- 30107400
TI  - Optimizing the Design and Analysis of Clinical Trials for Antibacterials Against
      Multidrug-resistant Organisms: A White Paper From COMBACTE's STAT-Net.
AB  - Innovations are urgently required for clinical development of antibacterials
      against multidrug-resistant organisms. Therefore, a European, public-private
      working group (STAT-Net; part of Combatting Bacterial Resistance in Europe
      [COMBACTE]), has reviewed and tested several innovative trials designs and
      analytical methods for randomized clinical trials, which has resulted in 8
      recommendations. The first 3 focus on pharmacokinetic and pharmacodynamic
      modeling, emphasizing the pertinence of population-based pharmacokinetic models,
      regulatory procedures for the reassessment of old antibiotics, and rigorous
      quality improvement. Recommendations 4 and 5 address the need for more sensitive
      primary end points through the use of rank-based or time-dependent composite end
      points. Recommendation 6 relates to the applicability of hierarchical nested
      trial designs, and the last 2 recommendations propose the incorporation of
      historical or concomitant trial data through Bayesian methods and/or platform
      trials. Although not all of these recommendations are directly applicable, they
      provide a solid, evidence-based approach to develop new, and established,
      antibacterials and address this public health challenge.

PMID- 30107404
TI  - The Effects of Add-on Fronto-Temporal Transcranial Direct Current Stimulation
      (tDCS) on Auditory Verbal Hallucinations, Other Psychopathological Symptoms, and
      Insight in Schizophrenia: A Randomized, Double-Blind, Sham-Controlled Trial.
AB  - Background: The efficacy of fronto-temporal transcranial direct current
      stimulation in treating auditory verbal hallucinations and other
      psychopathological symptoms of schizophrenia patients has been examined in a
      small number of clinical trials with limited sample sizes, but the results are
      mixed. Fronto-temporal transcranial direct current stimulation has also been
      demonstrated to enhance patients' insight into their mental illness in an open
      label pilot study. The current investigation aimed to investigate the therapeutic
      effects of fronto-temporal transcranial direct current stimulation on the
      severity of auditory verbal hallucinations, other schizophrenia symptoms, and
      insight in a large double blind, randomized, sham-controlled trial. Methods:
      Sixty patients with medication-refractory auditory verbal hallucinations were
      randomized over 2 conditions: transcranial direct current stimulation with 2-mA,
      twice-daily sessions for 5 consecutive days, with anodal stimulation to the left
      prefrontal cortex and cathodal stimulation to the left temporo-parietal junction,
      and sham treatment. Results: Fronto-temporal transcranial direct current
      stimulation failed to cause significant changes in the severity of auditory
      verbal hallucinations and other schizophrenia symptoms. The levels of insight
      into illness (effect size=0.511, P<.001) and positive symptoms (effect
      size=0.781, P<.001) were largely promoted by 5 days of transcranial direct
      current stimulation relative to sham treatment. The beneficial effects on the 2
      insight dimensions remained 1 month after transcranial direct current
      stimulation. Conclusions: Fronto-temporal transcranial direct current stimulation
      is not more effective for auditory verbal hallucinations and other schizophrenia
      symptoms than sham treatment. But the results of transcranial direct current
      stimulation-associated improvement in awareness of illness and positive symptoms
      show promise and provide a new direction for future research into insight
      promotion interventions in schizophrenia.

PMID- 30107406
TI  - Time to onset of type 2 diabetes mellitus in Ghana.
AB  - Background: Type 2 diabetes affects an increasing number of Ghanaians. The timing
      of the onset of diabetes is linked to several other co-morbid conditions, yet no
      study has examined the timing of the onset of type 2 diabetes in Ghana. Methods:
      To fill this gap in the literature, this study applied logit models to data
      extracted from the medical records at the Diabetes Clinic of the Komfo Anokye
      Teaching Hospital in Kumasi, Ghana. Gender-specific models were also estimated.
      Results: The results show that obesity was a significant predictor of the timing
      of the first onset of diabetes among both males and females. Women with high
      school education compared with no formal education, and female employees compared
      with the unemployed were more likely to experience an early onset of type 2
      diabetes. Conclusion: Policymakers must educate Ghanaians about behaviors that
      will reduce their risk of obesity and diabetes.

PMID- 30107407
TI  - Non-steroidal anti-inflammatory drugs and the risk of out-of-hospital cardiac
      arrest: a case-control study.
AB  - Aims: Non-steroidal anti-inflammatory drugs (NSAIDs), particularly selective COX
      2 inhibitors, are associated with an increased risk of cardiovascular adverse
      events. However, the association between these drugs and out-of-hospital cardiac
      arrest with electrocardiogram-documented ventricular tachycardia/ventricular
      fibrillation (VT/VF-OHCA) has not been studied yet. This study was aimed to
      evaluate the association between the use of selective COX-2 inhibitors or
      conventional NSAIDs and VT/VF-OHCA compared with non-use. Methods and results: A
      case-control study was conducted among 2483 cases with VT/VF-OHCA from the
      AmsteRdam REsuscitation STudies (ARREST) registry, an ongoing Dutch registry of
      OHCA, and 10 441 non-VT/VF-OHCA-controls from the Dutch PHARMO Database Network,
      containing drug dispensing records of community pharmacies, over the period July
      2005-December 2011. Up to five controls were matched for age and sex to one case
      at the date of VT/VF-OHCA (index date). Odds ratios (ORs) and 95% confidence
      intervals (CIs) were calculated by conditional logistic regression analysis. Of
      the cases, 0.5% was currently exposed at the index date to selective COX-2
      inhibitors and 2.5% to conventional NSAIDs. Neither current use of selective COX
      2 inhibitors nor conventional NSAIDs were associated with an increased risk of
      VT/VF-OHCA (adjusted OR 1.11, 95% CI: 0.79-1.56 and adjusted OR 0.97, 95% CI:
      0.86-1.10, respectively) compared with non-use. Stratification for VT/VF-OHCA
      with presence/absence of acute myocardial infarction did not change these
      results. Conclusion: Exposure to selective COX-2 inhibitors or conventional
      NSAIDs was not associated with an increased risk of VT/VF-OHCA compared with non
      use.

PMID- 30107405
TI  - Estradiol-Dependent and -Independent Stimulation of Kiss1 Expression in the
      Amygdala, BNST, and Lateral Septum of Mice.
AB  - Kisspeptin, encoded by Kiss1, activates reproduction by stimulating GnRH neurons.
      Although most Kiss1 neurons are located in the hypothalamus, smaller Kiss1
      populations also reside in the medial amygdala (MeA), bed nucleus of the stria
      terminalis (BnST), and lateral septum (LS). However, very little is known about
      the regulation and function of these extra-hypothalamic Kiss1 neurons. This study
      focused on the roles and interactions of two signaling factors, estradiol (E2)
      and GABA, known to stimulate and inhibit, respectively, extra-hypothalamic Kiss1
      expression. First, using estrogen receptor (ER)alpha knockout (KO) and betaERKO
      mice, we demonstrated that Kiss1 in both the BnST and LS is stimulated by E2, as
      occurs in the MeA, and that this E2 upregulation occurs via ERalpha, but not
      ERbeta. Second, using GABABR KO and wild-type mice, we determined that whereas E2
      normally increases extra-hypothalamic Kiss1 levels, such upregulation by E2 is
      further enhanced by the concurrent absence of GABABR signaling in the MeA and LS,
      but not the BnST. Third, we demonstrated that when GABABR signaling is absent,
      the additional removal of gonadal sex steroids does not abolish Kiss1 expression
      in the MeA and BnST, and in some cases the LS. Thus, Kiss1 expression in these
      extra-hypothalamic regions is not solely dependent on E2 stimulation. Finally, we
      demonstrated a significant positive correlation between Kiss1 levels in the MeA,
      BnST, and LS, but not between these regions and the hypothalamus (anteroventral
      periventricular nucleus/periventricular nucleus). Collectively, our findings
      indicate that both E2 and GABA independently regulate all three extra
      hypothalamic Kiss1 populations, but their regulatory interactions may vary by
      brain region and additional yet-to-be-identified factors are likely involved.

PMID- 30107408
TI  - Erratum.

PMID- 30107409
TI  - Perspective: Novel Commercial Packaging and Devices for Complementary Feeding.
AB  - In recent years, so-called baby food pouches and other novel packaging and
      devices have been marketed for complementary feeding. To date, no experimental
      studies have been conducted to determine health and nutrition effects or the
      safety of baby food pouches and related feeding devices. Yet, these products hold
      the potential to fundamentally change the ways in which infants and children
      consume solid foods in infancy and early childhood. In this review, a selection
      of complementary feeding devices and their potential effects on breastfeeding,
      formula-feeding, safe and appropriate complementary feeding, and the timely
      transition to family foods are explored. Because manufacturers have innovated
      older designs of traditional feeding bottles and pacifiers for complementary
      feeding, perspectives on potential health effects and the safety of devices are
      drawn from research on feeding bottles and pacifiers. Recommendations include
      scaling up research on the safety, nutrition, and health impacts of commercial
      packaging and devices. In addition, manufacturers should ensure that devices
      conform to consumer product safety commission specifications and that
      instructions for use are in line with policies protecting pediatric dental
      health. Marketing of commercial devices and packaging should conform to the
      International Code of Marketing of Breastmilk Substitutes.

PMID- 30107410
TI  - Feeding and Reproductive Hosts of Spissistilus festinus (Say) (Hemiptera:
      Membracidae) Found in Californian Vineyards.
AB  - Grapevine red blotch virus (GRBV) currently poses a serious threat to the wine
      industry. The three-cornered alfalfa hopper (3CAH), Spissistilus festinus (Say)
      (Hemiptera: Membracidae), was recently shown in a greenhouse study to be a vector
      of GRBV in grapes. Feeding and reproductive status of 10 weed and 10 cover crop
      species commonly found in grape vineyards were evaluated in no-choice tests.
      Species confirmed as reproductive hosts were subsequently evaluated in choice
      tests to determine S. festinus oviposition preference. Spanish clover, dandelion,
      birdsfoot trefoil, common groundsel, field bindweed, magnus peas, bell beans,
      blando brome, purple vetch, black medick, subterranean clover, crimson clover,
      and woollypod vetch were all found to be reproductive hosts. The plant species
      that exhibited the greatest nymph emergence in each of the three groups tested
      for preference were all in the family Fabaceae. Knowledge of plant species
      present in vineyards that serve as alternative hosts for S. festinus can
      contribute to developing management strategies to mitigate virus spread.

PMID- 30107411
TI  - Catastrophic health payments: does the equivalence scale matter?
AB  - We present a revised method for estimating equivalence scales. Such scales are
      used to adjust household welfare to account for the size of the household, and
      are used extensively in the application of the World Health Organization's (WHO)
      methodology for the evaluation of catastrophic health payments. Applications of
      the WHO method are underpinned by early estimates that do not control for
      household income, and, therefore, are likely to overstate equivalence. Thus, in
      addition to revising the method, we update the scale estimates for one country,
      South Africa, using more recent data. South Africa is considered, because the end
      of Apartheid has led to extensive social and economic changes that have
      influenced household structure and, presumably, equivalence. We also present
      information on the possible degree to which earlier estimates are overstated, as
      well as the effect that has on other components of the WHO method, especially the
      determinants of out-of-pocket expenditures and catastrophic health payments. We
      find that, in the worst case, initial estimates could be overstated by as much
      46%, leading to the understatement of poverty lines by as much as 17%. Despite
      these large differences, the average incidence of catastrophe in health
      expenditure was largely unaffected. Instead, differences in scales affect
      conclusions related to the determinants of out-of-pocket payments and
      catastrophic health expenditures, as well as the distribution of catastrophe
      across household size. Given that South Africa has low levels of catastrophic
      health expenditure, the effect could be even larger in other countries, and,
      therefore, we recommend that researchers consider a range of scales, when
      examining catastrophic health expenditures.

PMID- 30107412
TI  - Breast milk prefusion F IgG as a correlate of protection against respiratory
      syncytial virus acute respiratory illness.
AB  - Background: Transplacental RSV antibody transfer has been characterized, but
      little is known about the protective effect of breast milk RSV-specific
      antibodies. Serum antibodies against the prefusion RSV fusion protein (pre-F)
      exhibit high neutralizing activity. We investigate protection of breast milk pre
      F antibodies against RSV acute respiratory infection (ARI). Methods: Breast milk
      at 1, 3, and 6 months postpartum and mid-nasal swabs during infant illness
      episodes were collected in mother-infant pairs in Nepal. 174 infants with and
      without RSV ARI were matched 1:1 by risk factors for RSV ARI. Pre-F IgA and IgG
      antibody levels were measured in breast milk. Results: The median breast milk pre
      F IgG antibody concentration before illness was lower in mothers of infants with
      RSV ARI (1.4, IQR 1.1-1.6 log10 ng/mL) than without RSV ARI (1.5, IQR: 1.3-1.8
      log10 ng/mL, p=0.001). There was no difference in median maternal pre-F IgA
      antibody concentrations in cases (1.7, IQR: 0.0-2.2 log10 ng/mL) versus controls
      (1.7, IQR: 1.2-2.2 log10 ng/mL, p=0.58). Conclusion: Low breast milk pre-F IgG
      antibodies before RSV ARI supports a potential role for pre-F IgG as a correlate
      of protection against RSV ARI. Induction of breast milk pre-F IgG may be a
      mechanism of protection for maternal RSV vaccines.

PMID- 30107413
TI  - Evaluation of CSF neurofilament light chain levels as a routine biomarker in a
      memory clinic.
AB  - Systematic evaluation of biomarkers in representative populations is needed to
      validate their clinical utility. In this work, we assessed the diagnostic
      performance of cerebrospinal fluid neurofilament light chain (NfL) in a
      neurocognitive clinical setting. A total of 51 patients with different cognitive
      clinical syndromes and 11 cognitively normal individuals were evaluated in a
      memory clinic in Argentina. Clinical conditions included: Mild cognitive
      impairment (MCI, n=12), Dementia of Alzheimer's Type (DAT, n=14), Behavioral
      variant Frontotemporal dementia (bvFTD, n=13), and Primary Progressive Aphasia
      [logopenic (lvPPA, n=6), semantic (svPPA, n=2), and non-fluent (nfvPPA, n=4)]. We
      quantified CSF NfL and core Alzheimer's disease biomarkers using commercially
      available ELISA kits. Cortical thickness was analyzed on brain MRI scans from 10
      controls and 10 patients. CSF NfL was significantly increased in MCI, FTD and DAT
      patients compared to controls (Kruskal-Wallis, p<0.0001). Interestingly, receiver
      operating characteristic (ROC) curve analysis showed the highest area under the
      curve (AUC) value when analyzing control versus bvFTD patients (AUC= 0.9441).
      Also, we observed a marginally significant correlation between NfL levels and
      left orbito-frontal cortex thickness in a small group of patients with FTD.
      Overall, our results further support CSF NfL as a promising biomarker in the
      diagnostic work up of bvFTD.

PMID- 30107414
TI  - Socioeconomic status and health-related quality of life among adults and older
      with overactive bladder.
AB  - Objective: To study the effect of socioeconomic status (SES) on health-related
      quality of life (HRQoL) among persons with overactive bladder (OAB). Design: A
      randomized HRQoL study was conducted from the year 2014 until the year 2016 based
      on the OAB pathology department of the regional clinical diagnostics center.
      Setting: The medical institutions where the study was conducted had outpatient
      care. Participants: The simple response frequency was 81%. A total of 1893 men
      and women with OAB aged 35-85 (average 58.3 years) were selected by blind random
      sampling. Included into the group of examined individuals were persons who
      diagnosis provided after the examination was OAB. Intervention: Evaluation of
      HRQoL was conducted using the SF-6D questionnaire. The OAB diagnosis was
      confirmed using the OAB-questionnaire and uroflowmetry. Main outcome measure(s):
      We hypothesized that the impact of SES on the HRQoL of patients with OAB has
      significant features. Results: Described for the first time were HRQoL measures
      in various SES levels within different ages of people suffering from OAB. The
      strongest relationship was identified between education level, professional
      activity and HRQoL measures; meanwhile the weakest relationship was between
      income and HRQoL measures. We also confirmed the efficiency of evaluating HRQoL
      while using SF-6D and SRH as an external standard. Conclusion: The improvement of
      HRQoL in persons with OAB is contingent upon increment in their level of
      awareness about the methods of OAB treatment and the effectiveness of treatment
      for severe symptoms of LUT pathology, increased social support and, possibly,
      physical activity.

PMID- 30107415
TI  - Hybrid Genome Evolution by Transposition: An Update.

PMID- 30107416
TI  - Clinical Outcomes With Therapeutic Drug Monitoring in Inflammatory Bowel Disease:
      A Systematic Review With Meta-Analysis.
AB  - Background and Aims: We undertook a systematic review and meta-analysis examining
      the effectiveness of therapeutic drug monitoring [TDM] to improve clinical
      outcomes in inflammatory bowel disease patients treated with anti-tumour necrosis
      factor alpha [anti-TNF] drugs. Methods: We searched MEDLINE, Epub Ahead of Print,
      EMBASE and Cochrane up to October 2017 for randomized trials [RCTs] and cohort
      studies comparing proactive or reactive TDM to each other or empiric care.
      Outcomes included clinical remission [primary], clinical relapse, endoscopic
      remission, anti-TNF response durability, cost and adverse events [secondary].
      Pooled odds ratios and mean differences were calculated. Results: The search
      identified nine studies [three RCTs, six observational], focused on infliximab
      maintenance therapy in adults. Neither proactive nor reactive TDM was associated
      with superior clinical remission rates compared to empiric dose optimization.
      However, evidence of a cost benefit, particularly for reactive TDM vs empiric
      care, was identified. In several studies, TDM, particularly proactive TDM, was
      associated with favourable outcomes related to durability of anti-TNF response,
      such as lower drug discontinuation rates compared to empiric care and reactive
      TDM, and lower relapse rates compared to empiric care. No consistent benefit was
      found for endoscopic or surgical outcomes. Conclusions: The existing limited
      evidence does not support an association between any TDM strategy and superior
      clinical remission rates but does support a cost savings benefit [particularly
      for reactive TDM] and suggests a potential benefit for anti-TNF durability
      [particularly proactive TDM]. Additional, longer-term studies are needed,
      particularly to further investigate proactive TDM, and to generate data on other
      anti-TNF agents, the induction period and paediatric populations.

PMID- 30107418
TI  - Patterns of Fish Reproduction at the Interface Between Air and Water.
AB  - SYNOPSIS: Although fishes by nature are aquatic, many species reproduce in such a
      way that their embryos are exposed to air either occasionally or constantly
      during incubation. We examine the ecological context and review specific examples
      of reproduction by fishes at the air-water interface, including fishes that do
      and do not breathe air. Four modes of reproduction at the air-water interface are
      described across 18 teleost Orders, from fresh water, estuaries and sea water.
      Mode 1, the most common type of reproduction by fishes at the air-water
      interface, includes 21 Families of mostly marine teleosts that spawn in water
      onto a substrate surface, on vegetation, or into hollow objects such as shells
      that will later be continuously or occasionally exposed to air. Although the eggs
      are emerged into air, many of these species do not emerge into air as adults, and
      only about half of them breathe air. Mode 2 involves six Families of freshwater
      fishes setting up and guarding a nest and guarding on the water surface, either
      with bubbles or in vegetation. Most of these species breathe air. In Mode 3,
      annual killifishes in at least two Families in seasonally dry habitats bury eggs
      in mud in temporary pools, then die before the next generation emerges. These
      species neither guard nests nor breathe air. Mudskippers (Gobiidae) breathe air
      and use Mode 4, excavating burrows in a soft substrate and then storing air in a
      subterranean chamber. In a variation of Mode 4, eggs are placed on bubbles within
      a nesting burrow by swamp eels (Synbranchidae). No fishes from basal taxa are
      known to place their embryos where they will be exposed to air, although most of
      these species breathe air as adults. The widespread but still rare, diverse forms
      of fish reproduction at the air-water interface across a broad taxonomic spectrum
      suggest repeated independent evolutionary events and strong selection pressure
      for adult fishes to protect their embryos from hypoxic waters, aquatic predators,
      pathogens, and UV radiation. Air-breathing by adult fishes appears to be de
      coupled from air exposure of developing embryos or aerial emersion of adults
      during spawning.

PMID- 30107417
TI  - The helicase Pif1 functions in the template switching pathway of DNA damage
      bypass.
AB  - Replication of damaged DNA is challenging because lesions in the replication
      template frequently interfere with an orderly progression of the replisome. In
      this situation, complete duplication of the genome is ensured by the action of
      DNA damage bypass pathways effecting either translesion synthesis by specialized,
      damage-tolerant DNA polymerases or a recombination-like mechanism called template
      switching (TS). Here we report that budding yeast Pif1, a helicase known to be
      involved in the resolution of complex DNA structures as well as the maturation of
      Okazaki fragments during replication, contributes to DNA damage bypass. We show
      that Pif1 expands regions of single-stranded DNA, so-called daughter-strand gaps,
      left behind the replication fork as a consequence of replisome re-priming. This
      function requires interaction with the replication clamp, proliferating cell
      nuclear antigen, facilitating its recruitment to damage sites, and complements
      the activity of an exonuclease, Exo1, in the processing of post-replicative
      daughter-strand gaps in preparation for TS. Our results thus reveal a novel
      function of a conserved DNA helicase that is known as a key player in genome
      maintenance.

PMID- 30107420
TI  - The Evolution of Bioresorbable Scaffolds.

PMID- 30107419
TI  - Quitting Failure and Success With and Without Using Medication: Latent Classes of
      Abstinence and Adherence to Nicotine Monotherapy, Combination Therapy, and
      Varenicline.
AB  - Introduction: Non-adherence to pharmacotherapies complicates studies of
      comparative pharmacotherapy effectiveness. Modeling adherence and abstinence
      simultaneously may facilitate analysis of both treatment acceptability and
      effectiveness. Methods: Secondary analyses of a three-arm randomized comparative
      trial of nicotine patch, varenicline, and combination nicotine patch and lozenge
      among adult daily smokers (N=1086) were conducted. Adherence rates collected via
      interactive voice response systems during the first 27 days of quitting were
      compared across treatment conditions. Repeated measures latent class analyses of
      adherence and abstinence in three-day parcels through 27 days of a quit attempt
      were conducted with treatment, demographic, and smoking history covariates.
      Results: Adherence varied across treatments, and was lowest for nicotine lozenge
      use in combination nicotine replacement therapy. Five latent classes that
      differed significantly in six-month abstinence rates were retained, including
      three subgroups of adherent participants varying in treatment response and two
      non-adherent groups varying in abstinence probabilities. Non-adherence was more
      likely among those receiving varenicline and combination NRT, relative to patch
      monotherapy. Varenicline and combination NRT did not promote abstinence among
      adherent latent classes, but did promote abstinence among those partially
      adherent, relative to patch alone. Combination therapy attenuated increased risk
      of treatment disengagement with more years smoking. Minority smokers, those high
      in dependence, and those with shorter past abstinence were at increased risk for
      low adherence and low abstinence latent classes. Conclusions: Varenicline and
      combination nicotine patch and lozenge are less likely to be used as directed and
      may not increase first-month abstinence better than patch alone when taken
      adherently.

PMID- 30107421
TI  - CABANA: after all, a positive trial.

PMID- 30107422
TI  - CABANA - the (not so) neutral study.

PMID- 30107423
TI  - The New Postgraduate Course in Heart Failure.

PMID- 30107424
TI  - Heart failure with preserved ejection fraction: unravelling an enigma.

PMID- 30107425
TI  - British Society of Heart Failure.

PMID- 30107426
TI  - CABANA Trial, another favourable view.

PMID- 30107427
TI  - Minutes between life and death.

PMID- 30107428
TI  - The CABANA Trial: an honourable view.

PMID- 30107429
TI  - The CABANA trial: A first glance at an important study.

PMID- 30107430
TI  - Posterior Cervical Laminoplasty for Resection Intradural Extramedullary Spinal
      Meningioma: 2-Dimensional Operative Video.
AB  - This operative video demonstrates a posterior cervical laminoplasty for the
      resection of a cervical intradural extramedullary meningioma. In addition, the
      natural history, treatment options, and potential complications are discussed.
      The patient is a 68-yr-old male who presented with left-hand grip weakness and
      paresthesias. Magnetic resonance imaging (MRI) demonstrated an enhancing mass
      that displacing the spinal cord anteriorly and causing severe flattening of the
      cord at C4 and C5. The patient underwent a posterior cervical laminoplasty for
      tumor resection. Removal of the dorsal elements with a high-speed drill was
      performed at C3, C4, and C5. A midline durotomy was performed and a large extra
      axial intradural tumor was encountered. The tumor was resected en bloc and
      specimens were sent for permanent pathological analysis. The dura was closed in a
      watertight fashion using 6-0 Prolene sutures. The laminoplasty was performed by
      using titanium miniplates and screws to reconstruct the dorsal bony elements, and
      the wound was closed in layers using sutures. There were no complications. Final
      pathology was consistent with a WHO grade I meningioma. Postoperative MRI
      demonstrated gross total resection. The patient's perioperative course was
      uncomplicated and his preoperative weakness completely resolved by time of
      discharge.

PMID- 30107431
TI  - Diversity of Bacterial Communities in the Intestinal Tracts of Two Geographically
      Distant Populations of Bactrocera dorsalis (Diptera: Tephritidae).
AB  - The oriental fruit fly, Bactrocera dorsalis (Hendel), is one of the most
      destructive agricultural pests and hosts diverse intestinal bacterial
      communities. We used 16S rRNA gene sequencing to investigate the microbial
      communities associated with the intestines of females and males from two B.
      dorsalis populations collected from Hainan and Guizhou Provinces of China. A
      total of 260,615 high-quality 16S rRNA gene reads with an average length of 253
      bp were obtained. Highly diverse bacterial communities were observed across
      individuals, with communities containing between 691 and 1,262 bacterial
      operational taxonomic units. In addition, 37 bacterial phyla, 65 classes, 130
      orders, 198 families, 201 genera, and 70 annotated species were identified,
      wherein the Proteobacteria were the most dominant phylum among all of the
      libraries, followed by the Firmicutes and Bacteroidetes. Bacterial community
      composition varied by host sex and geographic location of the populations. Female
      gut communities comprised fewer bacterial families than males, and females had
      lower relative abundances of 33 of the 35 most abundant families. In addition,
      female gut communities harbored greater abundances of Enterobacteriaceae than
      males. The Hainan population gut communities contained fewer bacterial families
      than those of the Guizhou populations. However, 5 of the 35 most abundant
      families were more abundant in communities from the Hainan population than those
      of the Guizhou population. The results of this study help us better understand
      the importance of symbiotic bacteria in B. dorsalis and provide a foundation for
      assessing the use of gut microorganisms as bio-control agents for these serious
      pests.

PMID- 30107433
TI  - Exploring circulatory shock and mortality in viper envenomation: a prospective
      observational study from India.
AB  - Background: Viper envenomation contributes to nearly 50% of snake-bite deaths in
      India, chiefly due to circulatory shock. The mechanisms leading to circulatory
      shock include bleeding, capillary leak syndrome (CLS) and myocardial depression.
      Pituitary-adrenal axis involvement in circulatory shock, though described, has
      not been fully elucidated. Aim: To identify predictors of circulatory shock and
      mortality in viper envenomation and explore the role of pituitary-adrenal axis in
      circulatory shock. Design: Prospective hospital-based observational study.
      Methods: Once a syndromic diagnosis of viper envenomation was made, relevant
      clinical and laboratory data were collected. Serum cortisol was estimated in
      those with circulatory shock. Post-mortem examination of pituitary, kidneys and
      adrenals was performed. Adjusted odds-ratios were calculated for respective risk
      factors for shock and mortality using multivariable logistic regression with
      backward elimination strategy. Results: Of 248 patients of viper envenomation
      treated at our hospital, circulatory shock was present in 19% and in-hospital
      mortality was 23%. CLS, circulatory shock, bleeding and requirement of > 20 vials
      of antivenom predicted mortality. Ischaemic and haemorrhagic necrosis of
      pituitary or adrenals was present in 51% of post-mortem specimens. Disseminated
      intravascular coagulation (DIC) and CLS were strong predictors of pituitary
      haemorrhage. Conclusion: Predictors of mortality - bleeding, CLS and requirement
      of high antivenom doses are warning signs which can alert clinicians to patients
      who may have poor outcomes. Our study points to a definite role of pituitary
      adrenal axis in circulatory shock supports the hypothesis that pituitary
      involvement in viper envenomation closely resembles Sheehan syndrome. The
      mechanism of pituitary involvement appears to be a result of increased
      susceptibility of the swollen gland secondary to CLS and micro thrombi deposition
      in DIC.

PMID- 30107432
TI  - A conserved motif is essential for the correct assembly of proglutelins and for
      their export from the endoplasmic reticulum in rice endosperm.
AB  - Rice glutelins are initially synthesized as 57-kDa precursors at the endoplasmic
      reticulum (ER) and are ultimately transported into protein storage vacuoles.
      However, the sequence motifs that affect proglutelin folding, assembly, and their
      export from the ER remain poorly defined. In this study, we characterized a
      mutant with nine amino acids deleted in the GluA2 protein, which resulted in
      specific accumulation of the GluA precursor. The deleted amino acids constitute a
      well-conserved sequence (LVYIIQGRG) in glutelins and all residues in this motif
      are necessary for ER export of GluA2. Immunoelectron microscopy and stable
      transgenic analyses indicated that proglutelins with deletion of this motif
      misassembled and aggregated through non-native intermolecular disulfide bonds,
      and were deposited in ER-derived protein bodies (PB-Is), resulting in conversion
      of PB-Is into a new type of PB. These results indicate that the conserved motif
      is essential for proper assembly of proglutelin. The correct assembly of
      proglutelins is critical for their segregation from prolamins in the ER lumen,
      which is essential for enabling the export of proglutelin from the ER and for the
      proper formation of PB-Is. We also found that the interchain disulfide bond
      between acidic and basic subunits is not necessary for their assembly, but it is
      required for proglutelin folding.

PMID- 30107434
TI  - Assessing genome assembly quality using the LTR Assembly Index (LAI).
AB  - Assembling a plant genome is challenging due to the abundance of repetitive
      sequences, yet no standard is available to evaluate the assembly of repeat space.
      LTR retrotransposons (LTR-RTs) are the predominant interspersed repeat that is
      poorly assembled in draft genomes. Here, we propose a reference-free genome
      metric called LTR Assembly Index (LAI) that evaluates assembly continuity using
      LTR-RTs. After correcting for LTR-RT amplification dynamics, we show that LAI is
      independent of genome size, genomic LTR-RT content, and gene space evaluation
      metrics (i.e., BUSCO and CEGMA). By comparing genomic sequences produced by
      various sequencing techniques, we reveal the significant gain of assembly
      continuity by using long-read-based techniques over short-read-based methods.
      Moreover, LAI can facilitate iterative assembly improvement with assembler
      selection and identify low-quality genomic regions. To apply LAI, intact LTR-RTs
      and total LTR-RTs should contribute at least 0.1% and 5% to the genome size,
      respectively. The LAI program is freely available on GitHub:
      https://github.com/oushujun/LTR_retriever.

PMID- 30107435
TI  - Acinetobacter baumannii K20 and K21 capsular polysaccharide structures establish
      roles for UDP-glucose dehydrogenase Ugd2, pyruvyl transferase Ptr2 and two
      glycosyltransferases.
AB  - Infections caused by Acinetobacter baumannii isolates from the major global
      clones, GC1 and GC2, are difficult to treat with antibiotics, and phage therapy,
      which requires extensive knowledge of the variation in the surface
      polysaccharides, is an option under consideration. The gene clusters directing
      the synthesis of capsular polysaccharide (CPS) in A. baumannii GC1 isolate A388
      and GC2 isolate G21 differ by a single glycosyltransferase (gtr) gene. They
      include genes encoding a novel UDP-glucose dehydrogenase (Ugd2) and a putative
      pyruvyl transferase (Ptr2). The composition and structures of the linear K20 and
      K21 tetrasaccharide repeats (K units) of the CPSs isolated from A338 and G21,
      respectively, were established by sugar analyses and Smith degradation along with
      1D and 2D 1H and 13C NMR spectroscopy. The K20 and K21 CPSs are the first known
      to include GlcpA produced by Ugd2 and d-galactose with an (R)-configured 4,6
      pyruvic acid acetal added by Prt2. The first sugar in the tetrasaccharide K units
      is 2-acetamido-4-amino-2,4,6-trideoxy-d-glucose (d-QuipNAc4N) that carries a 4-N
      [(S)-3-hydroxybutanoyl] group in some K units and a 4-N-acetyl group in the
      others. Accordingly, K unit polymerases WzyK20 and WzyK21 form a beta-d
      QuipNAc4NR-(1->2)-d-Galp bond. The K20 and K21 units differ only in the
      configuration of the glycosidic linkages of d-GlcpNAc allowing the unique
      inverting glycosyltransferases Gtr43 and the retaining glycosyltransferase Gtr45
      to be assigned to the formation of the beta-d-GlcpNAc-(1->4)-d-GlcpA and alpha-d
      GlcpNAc-(1->4)-d-GlcpA linkages, respectively.

PMID- 30107437
TI  - Can we predict inadequate response to allopurinol dose escalation? Analysis of a
      randomised controlled trial.
AB  - Objectives: To determine factors that predict inadequate serum urate (SU)
      lowering response in a randomized controlled trial of allopurinol dose escalation
      (DE) in gout. Methods: Participants undergoing allopurinol DE were classified as:
      complete response (CR)-reached target SU at month 9 and 12 of the DE phase or if
      still dose escalating at month 9 reached target SU by month 12; partial response
      (PR)-reached target at some stage but not fulfilling criteria for CR; or
      inadequate response (IR)-did not reach target SU at any time. Results: IR was
      uncommon, occurring in 13/150 (8.7%), compared with 82 (54.7%) CR, and 55 (36.6%)
      PR. Mean (s.e.m.) SU was higher at the end of the 12-month DE in IR compared with
      both CR and PR groups; 7.6 (0.31) vs 5.01 (0.06) and 5.97 (0.17) mg/dl
      respectively (P < 0.001). In univariate analysis, compete responders tended to be
      older, be receiving less allopurinol, have longer gout duration and were more
      likely to be New Zealand (NZ) European ethnicity, compared with IR+PR. Using
      multi-variate logistic regression analysis, only longer duration of gout and NZ
      European ethnicity remained significant independent predictors of CR. Baseline SU
      ? 8 mg/dl had a sensitivity of 69.2% and specificity of 85.1% in predicting IR.
      The odds ratio for an IR if baseline SU was ?8 mg/dl was 11.7 (95% CI 3.3, 41.2).
      Conclusion: A minority of people with gout never reach target SU when allopurinol
      dose is increased in a treat-to-target manner. Approximately one-third of those
      with SU ? 8mg/dl despite allopurinol ?300mg/d have an IR to DE. Trial
      registration: Australian New Zealand Clinical Trails Registry,
      https://www.anzctr.org.au, ACTRN12611000845932.

PMID- 30107438
TI  - Does the DOSPERT scale predict risk-taking behaviour during travel? A study using
      smartphones.
AB  - Background: Despite the continuing growth of international tourism, very little
      research has been done on the link between individual risk attitudes and health
      behaviours during travel. Our study uses a validated risk-taking questionnaire
      Domain-Specific Risk-Taking Scale (DOSPERT) and data from a smartphone
      application to study the association between pre-travel risk attitudes and the
      occurrence of behaviours during travel. Methods: A prospective cohort of
      travellers to Thailand used a smartphone application to answer a daily
      questionnaire about health behaviours and events. Prior to travel, participants
      completed the DOSPERT, a validated 30-item scale that assesses risk-taking and
      perception in five content domains: financial decisions, health/safety,
      recreational, ethical and social decisions. Multiple linear regression models
      were used to model the relationship between DOSPERT risk-taking subdomain score
      and health behaviour. Results: Of the 75 travellers that completed the study, 70
      (93.3%) completed the DOSPERT pre-travel. Men, backpackers and young travellers
      reported a higher willingness to take recreational risks than women, luxury
      travellers and older travellers. Incidence of drug and alcohol risk behaviours
      during travel, itching from mosquitoes, smoking and failing to use a seatbelt in
      automobiles while at home were all significantly associated with an individual's
      score on the health and safety DOSPERT subdomain. Conclusions: In our study,
      individual scores on risk-taking in the health and safety subdomain of the
      DOSPERT questionnaire seem to be predictive of health behaviours both during
      travel and at home. By pairing new methods of data collection with questionnaires
      such as DOSPERT that identify key traveller characteristics to intervene on,
      travel medicine doctors will be able to provide more specialised health advice,
      ensuring that all travellers receive well-rounded advice about the full range of
      health challenges they will face during travel.

PMID- 30107439
TI  - Sustained Response to Botulinum Toxin Type A in SUNA Sydrome.

PMID- 30107436
TI  - Tunable order-disorder continuum in protein-DNA interactions.
AB  - DNA-binding protein domains (DBDs) sample diverse conformations in equilibrium
      facilitating the search and recognition of specific sites on DNA over millions of
      energetically degenerate competing sites. We hypothesize that DBDs have co
      evolved to sense and exploit the strong electric potential from the array of
      negatively charged phosphate groups on DNA. We test our hypothesis by employing
      the intrinsically disordered DBD of cytidine repressor (CytR) as a model system.
      CytR displays a graded increase in structure, stability and folding rate on
      increasing the osmolarity of the solution that mimics the non-specific screening
      by DNA phosphates. Electrostatic calculations and an Ising-like statistical
      mechanical model predict that CytR exhibits features of an electric potential
      sensor modulating its dimensions and landscape in a unique distance-dependent
      manner, while DNA plays the role of a non-specific macromolecular chaperone.
      Accordingly, CytR binds its natural half-site faster than the diffusion
      controlled limit and even random DNA conforming to an electrostatic-steering
      binding mechanism. Our work unravels for the first time the synergistic features
      of a natural electrostatic potential sensor, a novel binding mechanism driven by
      electrostatic frustration and disorder, and the role of DNA in promoting distance
      dependent protein structural transitions critical for switching between specific
      and non-specific DNA-binding modes.

PMID- 30107440
TI  - Decomposition of time-dependent fluorescence signals reveals codon-specific
      kinetics of protein synthesis.
AB  - During protein synthesis, the nascent peptide chain traverses the peptide exit
      tunnel of the ribosome. We monitor the co-translational movement of the nascent
      peptide using a fluorescent probe attached to the N-terminus of the nascent
      chain. Due to fluorophore quenching, the time-dependent fluorescence signal
      emitted by an individual peptide is determined by co-translational events, such
      as secondary structure formation and peptide-tunnel interactions. To obtain
      information on these individual events, the measured ensemble fluorescence signal
      has to be decomposed into position-dependent intensities. Here, we describe mRNA
      translation as a Markov process with specific fluorescence intensities assigned
      to the different states of the process. Combining the computed stochastic time
      evolution of the translation process with a sequence of observed ensemble
      fluorescence time courses, we compute the unknown position-specific intensities
      and obtain detailed information on the kinetics of the translation process. In
      particular, we find that translation of poly(U) mRNAs dramatically slows down at
      the fourth UUU codon. The method presented here detects subtle differences in the
      position-specific fluorescence intensities and thus provides a novel approach to
      study translation kinetics in ensemble experiments.

PMID- 30107441
TI  - Single Amino Acid Change in 6-Phosphogluconate Dehydrogenase from Synechocystis
      Conveys Higher Affinity for NADP+ and Altered Mode of Inhibition by NADPH.
AB  - In the oxidative pentose phosphate pathway, 6-phosphogluconate dehydrogenase
      (6PGDH, EC 1.1.1.44) is one of the enzymes that catalyzes reactions generating
      NADPH. The model cyanobacterium Synechocystis sp. PCC 6803 is widely studied for
      numerous applications; however, biochemical knowledge of the NADPH production
      pathway in Synechocystis sp. PCC 6803 is limited. In this study, we conducted
      biochemical analysis of a 6-phosphogluconate dehydrogenase from Synechocystis sp.
      PCC 6803 (Sy6PGDH). We found that Sy6PGDH has unconventional characteristics,
      that is, the highest kcat value and non-competitive inhibition by NADPH.
      Additionally, phylogenetic analysis of cyanobacterial 6PGDHs revealed that an
      amino acid residue at position 42 in Sy6PGDH is highly conserved for each order
      of cyanobacteria, but Sy6PGDH is phylogenetically unique. In Sy6PGDH, a single
      amino acid substitution at position 42 from serine to threonine enhanced the
      affinity for NADP+ and altered the mode of inhibition by NADPH. The amino acid
      substitution equivalent to serine-42 also altered the affinity for NADP+ and mode
      of inhibition by NADPH in Arthrospira platensis. These data suggested that an
      amino acid residue corresponding to position 42 in Sy6PGDH is one of the
      important residues that possibly determines the function of cyanobacterial
      6PGDHs.

PMID- 30107442
TI  - A case with tumour-induced osteomalacia misdiagnosed as axial spondyloarthritis.

PMID- 30107444
TI  - Dietary Phosphorus and Ambulatory Blood Pressure in African Americans: The
      Jackson Heart Study.
AB  - Background: Higher dietary phosphorus is associated with left ventricular
      hypertrophy and mortality, which are blood pressure (BP)-related outcomes. For
      this reason, we hypothesized that dietary phosphorus may be associated with
      adverse clinic and ambulatory BP patterns. Methods: Our study included 973
      African-American adults enrolled in the Jackson Heart Study (2000-2004) with 24
      hour ambulatory BP monitoring (ABPM) data at baseline. We quantified dietary
      phosphorus from a validated food frequency questionnaire (FFQ) as the following:
      1) absolute daily intake, 2) ratio of phosphorus-to-protein intake, 3) phosphorus
      density, and 4) energy-adjusted phosphorus intake. Using multivariable linear
      regression, we determined associations between dietary phosphorus intake and
      systolic BP (SBP), diastolic BP (DBP), and pulse pressure in clinic and over
      daytime, nighttime, and 24-hour periods from ABPM. Extent of nocturnal BP dipping
      was also assessed. Using logistic regression, we modeled relationships between
      dietary phosphorus intake and clinically-relevant qualitative BP phenotypes, such
      as masked, sustained or white coat hypertension and normotension. Results: There
      were no statistically significant associations between phosphorus intake and SBP
      or pulse pressure in adjusted models. Most metrics of higher phosphorus intake
      were associated with lower daytime, nighttime, and clinic DBP. Higher phosphorus
      intake was not associated with clinic or ABPM-defined hypertension overall, but
      most metrics of higher phosphorus intake were associated with lower odds of
      sustained hypertension compared to sustained normotension, white-coat
      hypertension, and masked hypertension. There were no associations between dietary
      phosphorus and nocturnal BP dipping. Conclusions: These data do not support a
      role for higher phosphorus intake and higher BP in African Americans.

PMID- 30107443
TI  - A patient-derived iPSC model revealed oxidative stress increases
      facioscapulohumeral muscular dystrophy-causative DUX4.
AB  - Double homeobox 4 (DUX4), the causative gene of facioscapulohumeral muscular
      dystrophy (FSHD), is ectopically expressed in the skeletal muscle cells of FSHD
      patients because of chromatin relaxation at 4q35. The diminished heterochromatic
      state at 4q35 is caused by either large genome contractions [FSHD type 1 (FSHD1)]
      or mutations in genes encoding chromatin regulators, such as SMCHD1 [FSHD type 2
      (FSHD2)]. However, the mechanism by which DUX4 expression is regulated remains
      largely unknown. Here, using a myocyte model developed from patient-derived
      induced pluripotent stem cells, we determined that DUX4 expression was increased
      by oxidative stress (OS), a common environmental stress in skeletal muscle, in
      both FSHD1 and FSHD2 myocytes. We generated FSHD2-derived isogenic control clones
      with SMCHD1 mutation corrected by clustered regularly interspaced short
      palindromic repeats (CRISPR)/ CRISPR associated 9 (Cas9) and homologous
      recombination and found in the myocytes obtained from these clones that DUX4
      basal expression and the OS-induced upregulation were markedly suppressed due to
      an increase in the heterochromatic state at 4q35. We further found that DNA
      damage response (DDR) was involved in OS-induced DUX4 increase and identified
      ataxia-telangiectasia mutated, a DDR regulator, as a mediator of this effect. Our
      results suggest that the relaxed chromatin state in FSHD muscle cells permits
      aberrant access of OS-induced DDR signaling, thus increasing DUX4 expression.
      These results suggest OS could represent an environmental risk factor that
      promotes FSHD progression.

PMID- 30107446
TI  - Exposure to Cadmium and Lead in Cigarette Smokers Who Switched to Electronic
      Cigarettes.
AB  - Introduction: E-cigarettes (ECs) seem to be a less harmful alternative for
      conventional cigarettes. This study aimed to assess whether the generated
      aerosols from ECs contain lower amount of Cd and Pb than cigarette smoke and to
      detect any changes in exposure to cadmium and lead among cigarette smokers who
      switched completely or partially to EC. Methods: EC aerosols and cigarette smoke
      were generated, and the determination of Cd and Pb in trapped samples and e
      liquids was performed by the Electrothermal Atomic Absorption Spectrometry
      (ETAAS) method. A cross-sectional, group-based survey was carried out using 156
      volunteers classified into groups of nonsmokers, EC-only users, dual EC users
      cigarette smokers and cigarette-only smokers. Using ETAAS, blood Cd and Pb levels
      were measured, and the results were compared by analysis of covariance. Results:
      Transfer of Cd and Pb to EC aerosol was found to be minimal, although the metals
      were present in the remaining e-liquid from tanks used for vapor generation. The
      geometric mean blood cadmium concentration adjusted for age and sex was 0.44 (95%
      confidence interval: 0.37 to 0.52) ug/L in the EC-only users, which was
      significantly lower than those in the smokers of 1.44 (1.16 to 1.78) and dual
      users of 1.38 (1.11 to 1.72). The blood lead geometric mean differed
      significantly only between nonsmokers of 11.9 (10.6 to 13.3) and smokers of 15.9
      (13.6 to 18.6). Conclusion: The study revealed that smokers who completely
      switched to e-cigarettes and quit smoking conventional cigarettes may
      significantly reduce their exposure to Cd and probably Pb.

PMID- 30107445
TI  - Pan-Filovirus Serum Neutralizing Antibodies in a Subset of Congolese Ebolavirus
      Infection Survivors.
AB  - One year after a Zaire ebolavirus (EBOV) outbreak occurred in the Boende Health
      Zone of the Democratic Republic of the Congo during 2014, we sought to determine
      the breadth of immune response against diverse filoviruses including EBOV,
      Bundibugyo (BDBV), Sudan (SUDV), and Marburg (MARV) viruses. After assessing the
      15 survivors, 5 individuals demonstrated some degree of reactivity to multiple
      ebolavirus species and, in some instances, Marburg virus. All 5 of these
      survivors had immunoreactivity to EBOV glycoprotein (GP) and EBOV VP40, and 4 had
      reactivity to EBOV nucleoprotein (NP). Three of these survivors showed serologic
      responses to the 3 species of ebolavirus GPs tested (EBOV, BDBV, SUDV). All 5
      samples also exhibited ability to neutralize EBOV using live virus, in a plaque
      reduction neutralization test. Remarkably, 3 of these EBOV survivors had plasma
      antibody responses to MARV GP. In pseudovirus neutralization assays, serum
      antibodies from a subset of these survivors also neutralized EBOV, BDBV, SUDV,
      and Tai Forest virus as well as MARV. Collectively, these findings suggest that
      some survivors of naturally acquired ebolavirus infection mount not only a pan
      ebolavirus response, but also in less frequent cases, a pan-filovirus
      neutralizing response.

PMID- 30107447
TI  - Safety and dose modification for patients receiving niraparib.

PMID- 30107448
TI  - Management of major organ involvement of Behcet's syndrome: a systematic review
      for update of the EULAR recommendations.
AB  - Objective: To assess the efficacy and safety of treatment modalities for major
      organ involvement of Behcet's syndrome (BS), in order to inform the update of the
      EULAR recommendations for the management of BS. Methods: A systematic literature
      review of all randomized controlled trials, controlled clinical trials, or open
      label trials assessing eye, vascular, nervous system or gastrointestinal system
      involvement of BS was performed. If controlled trials were not available for
      answering a specific research question, uncontrolled studies or case series were
      also included. Results: We reviewed the titles and abstracts of 3927 references
      and 161 studies met our inclusion criteria. There were only nine randomized
      controlled trials. Observational studies with IFN-alpha and monoclonal anti-TNF
      antibodies showed beneficial results for refractory uveitis. Meta-analysis of
      case-control studies showed that immunosuppressives decreased the recurrence rate
      of deep vein thrombosis significantly whereas anticoagulants did not. CYC and
      high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and
      postoperative complications in peripheral artery aneurysms. Beneficial results
      for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as
      first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies
      in refractory cases. Observational studies for nervous system involvement showed
      improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of
      case-control studies showed an increased risk of developing nervous system
      involvement with ciclosporin-A. Conclusion: The majority of studies related to
      major organ involvement that informed the updated EULAR recommendations for the
      management of BS were observational studies.

PMID- 30107449
TI  - Intravenous iron does not effectively correct preoperative anaemia in cardiac
      surgery: a pilot randomized controlled trial.
AB  - OBJECTIVES: Preoperative anaemia is a strong predictor of blood transfusion
      requirements and must be assessed for appropriate optimization before elective
      surgery. Iron therapy is a transfusion-sparing approach effective for increasing
      haemoglobin concentrations. However, its role in elective cardiac surgery and the
      optimal route of administration remain unknown. This single-centre, non-blinded,
      randomized, controlled trial compared the effectiveness of intravenous ferric
      carboxymaltose therapy with oral iron for anaemic patients undergoing elective
      cardiac surgery. METHODS: Fifty anaemic patients scheduled for elective cardiac
      surgery were randomized to receive either oral or intravenous iron therapy 3-8
      weeks preoperatively. Changes in haemoglobin concentration were measured. Blood
      transfusion and postoperative outcome data were collected. RESULTS: Preoperative
      median increases in haemoglobin were 1.0 g/l (interquartile range -3.25 to 7.25
      g/l) and 3.0 g/l (interquartile range -1.25 to 6.25 g/l) for patients receiving
      intravenous and oral iron, respectively (P = 0.42). The median first 12-h blood
      loss was significantly higher in the intravenous group (655 ml; interquartile
      range 162-1540 ml) compared to the oral group (313 ml; interquartile range 150
      1750 ml; P < 0.007). Median increments in serum ferritin were superior for the
      intravenous group (median difference 313 ug/l; interquartile range 228-496)
      compared to the oral group (median difference 5.5 ug/l; interquartile range -1.4
      to 19.4; P < 0.001). CONCLUSIONS: Increases in ferritin after intravenous iron
      administration were significantly greater than those after oral iron
      administration. There was no significant difference in haemoglobin increments
      between groups. Despite significantly higher intraoperative blood loss in the
      group receiving intravenous iron, blood transfusion requirements for both groups
      were not statistically different. Clinical trial registration: ISRCTN22158788.

PMID- 30107452
TI  - Reply.

PMID- 30107453
TI  - Work-place bullying reflects evolutionary selection of the fittest.

PMID- 30107451
TI  - Quarantine Vapor Heat Treatment of Papaya Fruit for Bactrocera dorsalis and
      Bactrocera cucurbitae (Diptera: Tephritidae).
AB  - The presence of quarantine insect pests in fruit export can impede trade with
      other countries. Therefore, to reduce the risk of possible quarantine pests in
      exported fruit, postharvest disinfestation treatment is essential. This study
      investigated the effects of vapor heat treatment (VHT) on oriental fruit fly
      (Bactrocera dorsalis Hendel (Diptera: Tephritidae)) and melon fly (Bactrocera
      cucurbitae Coquillett (Diptera: Tephritidae)) which are major pests for papaya
      fruits. For inoculated papaya fruits weighing 550 +/- 100 g, the optimal egg
      inoculation density, rearing conditions, and heat tolerance for each
      developmental stages of both fruit flies were determined, and then analyzed to
      determine their survival, and assess papaya fruit quality after treatment. Result
      of VHT of each developmental stage indicated that the eggs of B. dorsalis were
      the most heat tolerant at 45.6 degrees C. Efficacy test that determined the
      optimal mortality temperature was performed by subjecting 60 fruits infested with
      4,500 eggs to fruit core temperatures of 44.2, 45.2, 46.2, and 47.2 degrees C. It
      was found that when the papaya fruit core temperature increased at a heating rate
      of 0.0925 degrees C/min from room temperature to 47.2 degrees C in 3 h, fruit
      flies showed 100% mortality. Results of the confirmatory test using 300 papaya
      fruits also indicated 100% mortality at this temperature. Both fruit quality and
      injury test results demonstrated insignificant differences in color, appearance,
      soluble solids, or firmness of fruits before and after treatment. Thus, VHT
      effectively disinfested papaya fruits against both fruit fly species, thus making
      it a viable quarantine treatment for papaya fruits prior to their export.

PMID- 30107450
TI  - Role of nucleotide identity in effective CRISPR target escape mutations.
AB  - Prokaryotes use primed CRISPR adaptation to update their memory bank of spacers
      against invading genetic elements that have escaped CRISPR interference through
      mutations in their protospacer target site. We previously observed a trend that
      nucleotide-dependent mismatches between crRNA and the protospacer strongly
      influence the efficiency of primed CRISPR adaptation. Here we show that guanine
      substitutions in the target strand of the protospacer are highly detrimental to
      CRISPR interference and interference-dependent priming, while cytosine
      substitutions are more readily tolerated. Furthermore, we show that this effect
      is based on strongly decreased binding affinity of the effector complex Cascade
      for guanine-mismatched targets, while cytosine-mismatched targets only minimally
      affect target DNA binding. Structural modeling of Cascade-bound targets with
      mismatches shows that steric clashes of mismatched guanines lead to unfavorable
      conformations of the RNA-DNA duplex. This effect has strong implications for the
      natural selection of target site mutations that lead to effective escape from
      type I CRISPR-Cas systems.

PMID- 30107454
TI  - Sedentary behaviour at work-an underappreciated occupational hazard?

PMID- 30107455
TI  - Oncological occupational physicians: meeting the challenge of an ageing
      workforce.

PMID- 30107456
TI  - Editorial: Cross-disciplinary biofilm research-an introduction to the fourth
      thematic issue on biofilms.

PMID- 30107458
TI  - Integrated analysis of the yeast NADPH-regulator Stb5 reveals distinct
      differences in NADPH requirements and regulation in different states of yeast
      metabolism.
AB  - The Saccharomyces cerevisiae transcription factor (TF) Stb5 is known to be
      involved in regulating NADPH generation. We explored its role by combining DNA
      binding studies with transcriptome analysis at four environmental conditions that
      were selected to cover a range of different metabolic states. Using ChIP-exo, DNA
      binding targets of Stb5 were found to confirm many previously proposed binding
      targets, in particular genes encoding enzymes involved in NADPH generation and
      the pentose-phosphate (PP) pathway. Transcriptome analysis of an STB5 deletion
      strain revealed transcriptional changes in direct regulation targets of Stb5,
      including several PP pathway genes as well as additional novel regulatory
      targets, but interestingly not including the proposed PP pathway flux controlling
      enzyme Zwf1. Consistently, NADPH levels were found to decrease significantly with
      STB5 deletion in cultures with aerobic, glucose metabolism. We also found reduced
      growth for the STB5 deletion strain in similar conditions as those with reduced
      NADPH levels, supporting a role for Stb5 in NADPH generation through the PP
      pathway. We finally explored the flux distribution by genome scale modelling
      simulations and found a decreased flux in both NADPH generating as well as
      consuming reactions in the STB5 deletion strain.

PMID- 30107459
TI  - Terrorist attacks: a public health issue.

PMID- 30107460
TI  - Communications principles for inviting inquiry and exploration through science
      and data visualization.
AB  - Science, in the popular imagination, is about finding answers to questions.
      Scientists make discoveries, develop theories, and deliver those discoveries and
      theories to audiences with an interest in the truth as backed up by science. Well
      designed data visualization (dataviz), by contrast, can generate and address not
      only new questions but new kinds of questions. It has the particular quality of
      allowing its viewers, users and makers the ability to generate new inquiries, and
      to put them in a better place to answer them. Dataviz offers aesthetic and
      interactive platforms for discussion and inquiry that can help scientists to both
      do their work and better communicate their work to broader audiences.Here I will
      illustrate and examine case studies from multiple points along the rich and
      varied possibility space that opens up when science and dataviz work together. I
      will also introduce three communication principles that I have learned from my
      involvement with hundreds of dataviz projects over the years. Well-designed
      dataviz can help scientists and those involved with science find ways to navigate
      the multiple competing interests and priorities inherent in both communication to
      non-scientists and exploratory data-rich
      interfaces.http://sicb.org/meetings/2018/abstracts/correctsymposia.php.

PMID- 30107461
TI  - Illness perceptions and their association with 2 year functional status and
      change in patients with hand osteoarthritis.
AB  - Objective: To investigate the association between illness perceptions and
      disability both cross-sectionally and over 2 years in patients with hand OA.
      Methods: Illness perceptions and self-reported disability were assessed at
      baseline and after 2 years in 384 patients with primary hand OA (mean age 61
      years, 84% women, n = 312 with follow-up) with the Illness Perception
      Questionnaire - Revised (IPQ-R), Functional Index for Hand OA,
      Australian/Canadian Hand OA Index and HAQ. Risk ratios for high disability
      (highest quartile) at both time points were estimated for tertiles of IPQ-R
      dimensions, using Poisson regression. The mean IPQ dimension change difference
      between patients with and without disability progression (change Functional Index
      for Hand OA ? 1, Australian/Canadian Hand OA Index > 1.4, HAQ > 0.22) was
      estimated with linear regression. Analyses were adjusted for age, Doyle index and
      baseline score. Results: At baseline, stronger negative illness perceptions were
      associated with high disability. Baseline illness perceptions were also
      associated with high disability after 2 years, although adjustment made apparent
      that these associations were confounded by baseline disability status. Most
      illness perceptions changed over 2 years; understanding increased, OA was
      regarded as more chronic and fewer emotions and consequences and less personal
      and treatment control were experienced. The 2 year change in disability was
      different between patients with and without progression for the illness
      perceptions of more perceived consequences, symptoms, treatment control and
      emotions. Conclusion: Illness perceptions seemed to be implicated in disability
      and its progression. Our results suggest that interventions could focus on
      improving baseline disability, potentially using illness perceptions to
      accomplish this goal.

PMID- 30107462
TI  - Latent Class Analysis of E-cigarette Use Sessions in their Natural Environments.
AB  - Introduction: Delivery of nicotine and substances from electronic nicotine
      delivery systems, or e-cigarettes, depends in-part on how users puff on the
      devices. Little is known about variation in puffing behavior to inform testing
      protocols or understand if puffing behaviors result in increased exposure to
      emissions. Methods: We analyzed puff topography data collected using a wireless
      portable use monitor (wPUMTM) continuously over 2 weeks among N = 34 current
      second generation ecigarette users in their everyday lives. For each puff, the
      wPUMTM recorded date, time, duration, volume, flow rate, and inter-puff interval.
      Results: We defined use session and classes at the session level using multilevel
      latent profile analysis, resulting in two session classes and three person types.
      Session class 1 was characterized by 14.7 puffs per session (PPS), low puff
      volume (59.9 ml), flow rate (28.7 ml/sec), and puff duration (202.7 sec x 100).
      Session class 2 was characterized by 16.7 PPS with a high puff volume (290.9 ml),
      flow rate (71.5 ml/sec), and puff duration (441.1 sec x 100). Person class 1 had
      almost exclusively "light" class 1 sessions (98.0%), whereas person class 2 had a
      majority of "heavy" class 2 sessions (60.7%) and person class 3 had a majority of
      "light" class 1 sessions (75.3%) but some "heavy" class 2 sessions (24.7%).
      Conclusion: Results suggest there are different session topography patterns among
      e-cigarette users. Further assessment is needed to determine if some users have
      increased exposure to constituents and/or health risks due to e-cigarettes.
      Implications: Our study examines topography characteristics in a users' natural
      setting to identify two classes of e-cigarette session behavior and three classes
      of users. These results suggest that it is important for studies on the health
      effects of e-cigarettes to take variation in user topography into account. It is
      crucial to accurately understand the topography profiles of session and user
      types to determine whether some users are at greater exposure to harmful or
      potentially harmful constituents (HPHCs) and risks from e-cigarettes as they are
      used by consumers.

PMID- 30107463
TI  - Adapting a health equity tool to meet professional needs (Quebec, Canada).
AB  - While numerous tools are available to better incorporate equity into population
      health actions, they are limited mainly by their lack of adaptation to
      professional practices and organizational realities. A study was conducted in
      Quebec to identify and understand, from the perspective of future users,
      conditions that would facilitate use of a tool (Reflex-ISS) targeted at
      supporting collaborative action to improve consideration of social inequalities
      in health (SIH) within population health actions. Concept mapping and focus
      groups were implemented as complementary methods for investigating the
      conditions. Significant results that emerged were strong participant interest in
      the tool and the need for resources to better take SIH into account. The
      conditions for use that were identified referred to the tool itself (user
      friendliness and literacy) and to resources for appropriating the tool,
      competency development, as well as the role and responsibilities of organizations
      and policies in promoting use of the tool in daily activities and more
      fundamentally in acting against SIH in general. Models for organizational
      innovation give an idea of the dimensions that need to be considered to
      strengthen the integration of equity into organizations and to support the
      changes in practice that result from using the tool. They provide a reminder that
      a health equity tool cannot be the cornerstone of an organizational strategy to
      fight against SIH; rather, it must be incorporated as part of a systemic strategy
      of professional and organizational development.

PMID- 30107464
TI  - Hsp90 inhibitor AT-533 blocks HSV-1 nuclear egress and assembly.
AB  - Heat shock protein 90 (Hsp90) has been identified as an essential host factor for
      the infection and replication of several viruses, including HSV-1. Recent works
      have clearly shown that Hsp90 plays a role in the early stages of HSV-1
      infection, including nuclear import and DNA replication. However, the role of
      Hsp90 in the late stages of HSV-1 infection remains unclear. In this study, we
      found that Hsp90 was up-regulated during late viral infection. Treatment with the
      Hsp90 inhibitor AT-533 significantly decreased the intracellular and
      extracellular virus titers, and strongly inhibited nucleocapsid egress from the
      nucleus. More detailed studies revealed that AT-533 inhibited the nuclear egress
      of the viral nucleocapsid by suppressing the expression and translocation of
      nuclear-associated proteins pUL31 and pUL34. In addition, we found that AT-533
      hindered the assembly of virus particles possibly though affecting the
      localization of glycoproteins in the endoplasmic reticulum and Golgi apparatus.
      These results thus invoke a new role for Hsp90 in the nucleocapsid egress and
      viral maturation of HSV-1, and further promote the development of Hsp90
      inhibitors as potential anti-HSV-1 drugs.

PMID- 30107465
TI  - The consequences of medically important invasive arthropods: The longhorned tick,
      Haemaphysalis longicornis.

PMID- 30107467
TI  - Relationship Between Brain Arterial Pathology and Neurocognitive Performance
      Among Individuals With Human Immunodeficiency Virus.
AB  - Background: Human immunodeficiency virus-positive (HIV+) individuals have higher
      rates of cognitive impairment and cerebrovascular disease compared with
      uninfected populations. We hypothesize that cerebrovascular disease, specifically
      brain large artery disease, may play a role in HIV-associated neurocognitive
      disorders (HAND). Methods: Participants (N = 94) in the Manhattan HIV Brain Bank
      study were followed on average 32 +/- 33 months with repeated neuropsychological
      examinations until death. We used five cognitive domains (motor, processing
      speed, working memory, verbal fluency, and executive functioning) to assess ante
      mortem performance. We quantified the diameter of the lumen and arterial wall
      thickness obtained during autopsy. The diagnoses of HAND were attributed using
      the American Academy of Neurology nosology. We used generalized linear mixed
      model to account for repeated measures, follow-up time, and codependence between
      arteries. Models were adjusted for demographics, viral loads, CD4 counts, history
      of opportunistic infections, and vascular risks. Results: We included 94 HIV+
      individuals (mean age 56 +/- 8.3, 68% men, 54% African American). In adjusted
      models, there was an association between arterial wall thickness and global
      cognitive score (B = -0.176, P value = .03), processing speed (B = -0.175, P =
      .05), and verbal fluency (B = -0.253, P = .02). Participants with incident or
      worsening HAND had thicker brain arterial walls (B = 0.523 +/- 0.234, P = .03)
      and smaller arterial lumen (B = -0.633 +/- 0.252, P = .01). Conclusions: We
      report here a novel association between brain arterial wall thickening and poorer
      ante mortem cognitive performance and diagnosis of incident or worsening HAND at
      death. Strategies to preserve the arterial lumen or to prevent wall thickening
      may impact HAND.

PMID- 30107466
TI  - Infant breastfeeding and childhood general, visceral, liver, and pericardial fat
      measures assessed by magnetic resonance imaging.
AB  - Background: Although a longer duration of breastfeeding has been associated with
      a lower risk of childhood obesity, the impact on specific organ fat depots is
      largely unknown. Objective: We examined the associations of any breastfeeding,
      duration and exclusiveness of breastfeeding, and of age at introduction of solid
      foods with measures of general, visceral, and organ adiposity at 10 y. Design: In
      a population-based prospective cohort study in 4444 children, we obtained
      information on infant feeding by questionnaires. At the mean age of 9.8 y, we
      estimated body mass index from height and weight; fat mass index and fat-free
      mass index by dual-energy X-ray absorptiometry; and visceral fat index,
      pericardial fat index, and liver fat fraction by MRI. MRI scans were performed in
      a subgroup of 2646 children. Results: After adjustment for age and sex, we
      observed associations of infant feeding with all general, visceral, and organ fat
      outcomes, except for pericardial fat index, at the age of 10 y. After further
      adjustment for family-based sociodemographic, maternal lifestyle-related, and
      childhood factors, only the associations of shorter breastfeeding duration and
      nonexclusive breastfeeding with a lower fat-free mass index remained significant
      (P < 0.05). The associations of infant feeding with visceral fat index and liver
      fat fraction were attenuated to nonsignificant. Maternal education was found to
      be the strongest confounder. Conclusion: Our results suggest that the assoiations
      of any breastfeeding, duration and exclusiveness of breastfeeding, and age at the
      introduction of solid foods with general, visceral, and organ fat measures at the
      age of 10 y are largely explained by family-based sociodemographic factors.

PMID- 30107468
TI  - Comment on: T2Candida MR as a predictor of outcome in patients with suspected
      invasive candidiasis starting empirical antifungal treatment: a prospective pilot
      study.

PMID- 30107469
TI  - Endocrine-Metabolic Response in Patients Undergoing Multiple Body Contouring
      Surgeries After Massive Weight Loss.
AB  - Background: The endocrine-metabolic response to trauma is directly related to its
      magnitude, but little is known about the adverse effects of combined surgical
      procedures on morbidity. Objective: To evaluate risk factor in patients
      undergoing multiple body contouring surgeries after massive weight loss by
      measuring the endocrine-metabolic response. Methods: This prospective,
      randomized, interventional study included 46 massive weight loss patients with a
      weight loss higher than 30% of their (body mass index) BMI, who were referred for
      body contouring surgery. Patients were randomly allocated to the control group (n
      = 10) or intervention group (n = 36), which in turn was divided into three
      subgroups (n = 12, each), according to BMI, surgical time, and scar length
      values. Blood samples were collected from all patients at different time points
      for the assessment of biological stress markers. Results: Patients in the higher
      ranges of BMI, operating time, with more extensive scar length had levels of IL-6
      significantly higher in the immediate postoperative period compared with
      baseline. Concentrations of noradrenaline were significantly higher 24 h after
      surgery compared with baseline only in patients in the higher range of operating
      time. A higher level of IL-6 at 72 hours after surgery when compared with
      baseline was associated with a more extensive scar length. No significant
      differences in the levels of other biological stress markers were found.
      Conclusions: The combination of surgical procedures did not significantly affect
      the concentrations of most biological stress markers. Operating time was the
      variable that most influenced the increase in plasma concentrations of stress
      markers.

PMID- 30107470
TI  - Exchange Rate and Risk of Noise-Induced Hearing Loss in Construction Workers.

PMID- 30107471
TI  - The Effect of Reciprocity Priming on Organ Donor Registration Intentions and
      Behavior.
AB  - Background: Internationally the demand for organ transplants far exceeds the
      available supply of donated organs. Purpose: We examine if a digital reciprocity
      prime based on reciprocal altruism can be used to increase organ donor
      registration intentions and behavior. Methods: Four hundred twenty participants
      (223 females) from England and Scotland aged 18+ who were not currently
      registered organ donors were randomized by block allocation using a 1:1 ratio to
      receive either a reciprocity prime or control message. After manipulation, they
      were asked to indicate their organ donation intentions and whether or not they
      would like to be taken to an organ donation registration and information page.
      Results: In line with our previous work, participants primed with a reciprocity
      statement reported greater intent to register as an organ donor than controls
      (using a 7-point Likert scale where higher scores = greater intention; prime mean
      [SD] = 4.3 [1.6] vs. control mean [SD] = 3.7 [1.4], p <= .001, d = 0.4 [95%
      confidence interval [CI] = 0.21-0.59]). There was again however, no effect on
      behavior as rates of participants agreeing to receive the donation register web
      link were comparable between those primed at 11% (n = 23/210) (95% CI = 7.4-16.0)
      and controls at 12% (n = 25/210) (95% CI = 8.1-17.1), X2 (1) = 0.09, p = .759.
      Conclusions: Reciprocal altruism appears useful for increasing intention towards
      joining the organ donation register. It does not, however, appear to increase
      organ donor behavior.

PMID- 30107472
TI  - Clinical outcomes of solitary atrial flutter patients using anticoagulation
      therapy: a national cohort study.
AB  - Aims: Anticoagulation therapy is indicated to prevent stroke in atrial flutter
      (AFL) and atrial fibrillation (AF) patients. However, the outcomes of solitary
      AFL patients may differ from those with AFL who develop AF during follow-up. This
      study aimed to investigate the differences in clinical outcomes: (i) among
      patients with solitary AFL, AF, and AFL developing AF thereafter and (ii) between
      solitary AFL patients with vs. without anticoagulation therapy. Methods and
      results: This nationwide cohort study enrolled patients with solitary AFL,
      solitary AF, and AFL developing AF from a 12 years National Health Insurance
      Research Database in Taiwan. There were 230 367 patients without anticoagulation
      therapy in the solitary AF cohort, 8064 in the solitary AFL cohort, and 4495 in
      the AFL with AF cohort. The AFL with AF and solitary AF cohorts had higher
      incidences of ischaemic stroke and major bleeding than the solitary AFL cohort.
      Solitary AFL patients with anticoagulation therapy had a lower ischaemic stroke
      rate than those without (P < 0.05) at the level of a CHA2DS2-VASc score >=3.
      Solitary AFL patients with anticoagulation therapy had a higher intracranial
      haemorrhage rate than those without (P < 0.05) at the level of a CHA2DS2-VASc
      score <=3. Net clinical outcomes including ischaemic stroke, systemic
      embolization, and major bleeding favoured anticoagulation use in solitary AFL
      patients with a CHA2DS2-VASc score >=4. Conclusion: Solitary AFL patients without
      anticoagulation therapy had better clinical outcomes than AFL patients developing
      AF in this study. Anticoagulation therapy may offer the best net clinical outcome
      for solitary AFL patients with a CHA2DS2-VASc score >=4.

PMID- 30107473
TI  - Six-Month Comparative Analysis Monitoring the Progression of the Largest Diameter
      of the Sweating Inhibition Halo of Different Botulinum Toxins Type-A.
AB  - Background: Excessive sweating is a clinical condition that can be improved with
      type-A botulinum toxin (BTX-A). Objectives: To evaluate and compare the largest
      diameter of sweating inhibition halo (SIH) of 5 different commercially available
      BTX-A, in five different doses, in a 6-month-long clinical evaluation. Methods:
      Twenty-five adult female volunteers were injected in the dorsal trunk area with
      both 100 units (100UI) and 500 units (500UI) BTX-A products, reconstituted in a
      ratio of 1:2.5, respectively. Products were applied in five different
      concentrations (1:2.5U, 2:5U, 3:7.5U, 4:10U, and 5:12.5U). After 30, 60, 90, 120,
      150, and 180 days, a starch-iodine test was performed to obtain the largest
      diameter of each SIH. Results: The higher the number of units used, the larger
      the SIH p<0.05 for all BTX-A. However, Botox(r), Botulift(r), Dysport(r), and
      Prosigne(r) have pretty likewise SIH along the study, with some few differences
      for some doses and months between one and another. However, Xeomin(r) is the BTX
      A with the smallest SIH, in comparison with all others, in any dose and period.
      Conclusions: Differences were observed among all brands of BTX-As, based on dose
      and time after injection. Xeomin(r) provides the smallest SIH in comparison with
      others BTX-A.

PMID- 30107474
TI  - Alan S. Rabson (1926-2018).

PMID- 30107477
TI  - Safety and Efficacy of Smooth Surface Tissue Expander Breast Reconstruction.
AB  - Background: Traditional two-stage breast reconstruction involves placement of a
      textured surface tissue expander (TTE). Recent studies have demonstrated textured
      surface devices have higher propensity for bacterial contamination and biofilm
      formation. Objectives: The purpose of this study was to evaluate the safety and
      efficacy of smooth surface tissue expanders (STE) in immediate breast
      reconstruction. Methods: We retrospectively reviewed consecutive women undergoing
      STE breast reconstruction from 2016 to 2017 at three institutions. Indications
      and outcomes were evaluated. Results: One hundred twelve patients underwent STE
      reconstruction (75 subpectoral, 37 prepectoral placement) receiving 173 devices
      with a mean follow up of 14.1 months. Demographics of patients included average
      age of 53 years and average BMI of 27.2 kg/m2, and 18.6% received postmastectomy
      radiation therapy. Overall complication rates were 15.6%, and included mastectomy
      skin flap necrosis (MSFN) (10.4%), seroma (5.2%), expander malposition (2.9%),
      and infection requiring intravenous antibiotic therapy (3.5%). Six (3.5%)
      unplanned reoperations with explantation were reported for 3 infections and 3
      patients requesting change of plan with no reconstruction. Conclusions: STEs
      represent a safe and efficacious alternative to TTE breast reconstruction with at
      least equitable outcomes. Technique modification including tab fixation, ADM
      pocket control, postoperative bra support, and suture choice may contribute to
      observed favorable outcomes and are reviewed. Early results for infection control
      and explantation rate are encouraging and warrant comparative evaluation for
      potential superiority over TTEs in a prospective randomized trial.

PMID- 30107475
TI  - Perspective: Food-Based Dietary Guidelines in Europe-Scientific Concepts, Current
      Status, and Perspectives.
AB  - Food-based dietary guidelines (FBDGs) are important tools for nutrition policies
      and public health. FBDGs provide guidelines on healthy food consumption and are
      based on scientific evidence. In the past, disease prevention and nutrient
      recommendations dominated the process of establishing FBDGs. However, scientific
      advances and social developments such as changing lifestyles, interest in
      personalized health, and concerns about sustainability require a reorientation of
      the creation of FBDGs to include a wider range of aspects of dietary behavior.
      The present review evaluates current European FBDGs with regard to the concepts
      and aspects used in their derivation, and summarizes the major aspects currently
      discussed to be considered in future establishment or updates of FBDGs. We
      identified English information on official European FBDGs through an Internet
      search (FAO, PubMed, Google) and analyzed the aspects used for their derivation.
      Furthermore, we searched literature databases (PubMed, Google Scholar) for
      conceptional considerations dealing with FBDGs. A total of 34 out of 53 European
      countries were identified as having official FBDGs, and for 15 of these,
      documents with information on the scientific basis could be identified and
      described. Subsequently, aspects underlying the derivation of current FBDGs and
      aspects considered in the literature as important for future FBDGs were
      discussed. Eight aspects were identified: diet-health relations, nutrient supply,
      energy supply, dietary habits, sustainability, food-borne contaminants, target
      group segmentation, and individualization. The first 4 have already been widely
      applied in existing FBDGs; the others have almost never been taken into account.
      It remains a future challenge to (re)conceptionalize the development of FBDGs, to
      operationalize the aspects to be incorporated in their derivation, and to convert
      concepts into systematic approaches. The current review may assist national
      expert groups and clarifies the options for future development of local FBDGs.

PMID- 30107476
TI  - Caloric restriction inhibits mammary tumorigenesis in MMTV-ErbB2 transgenic mice
      through the suppression of ER and ErbB2 pathways and inhibition of epithelial
      cell stemness in premalignant mammary tissues.
AB  - Caloric intake influences the onset of many diseases, including cancer. In
      particular, caloric restriction (CR) has been reported to suppress mammary
      tumorigenesis in various models. However, the underlying cancer preventive
      mechanisms have not been fully explored. To this end, we aimed to characterize
      the anticancer mechanisms of CR using MMTV-ErbB2 transgenic mice, a well
      established spontaneous ErbB2-overexpressing mammary tumor model, by focusing on
      cellular and molecular changes in premalignant tissues. In MMTV-ErbB2 mice with
      30% CR beginning at 8 weeks of age, mammary tumor development was dramatically
      inhibited, as exhibited by reduced tumor incidence and increased tumor latency.
      Morphogenic mammary gland analyses in 15- and 20-week-old mice indicated that CR
      significantly decreased mammary epithelial cell (MEC) density and proliferative
      index. To understand the underlying mechanisms, we analyzed the effects of CR on
      mammary stem/progenitor cells. Results from fluorescence-activated cell sorting
      analyses showed that CR modified mammary tissue hierarchy dynamics, as evidenced
      by decreased luminal cells (CD24highCD49flow), putative mammary reconstituting
      unit subpopulation (CD24highCD49fhigh) and luminal progenitor cells
      (CD61highCD49fhigh). Mammosphere and colony-forming cell assays demonstrated that
      CR significantly inhibited mammary stem cell self-renewal and progenitor cell
      numbers. Molecular analyses indicated that CR concurrently inhibited estrogen
      receptor (ER) and ErbB2 signaling. These molecular changes were accompanied by
      decreased mRNA levels of ER-targeted genes and epidermal growth factor
      receptor/ErbB2 family members and ligands, suggesting ER-ErbB2 signaling cross
      talk. Collectively, our data demonstrate that CR significantly impacts ER and
      ErbB2 signaling, which induces profound changes in MEC reprogramming, and mammary
      stem/progenitor cell inhibition is a critical mechanism of CR-mediated breast
      cancer prevention.

PMID- 30107478
TI  - Neonatal lactocrine deficiency affects the adult porcine endometrial
      transcriptome at pregnancy day 13.
AB  - Reproductive performance of female pigs that do not receive sufficient colostrum
      from birth is permanently impaired. Whether lactocrine deficiency, reflected by
      low serum immunoglobulin immunocrit (iCrit), affects patterns of endometrial gene
      expression during the periattachment period of early pregnancy is unknown. Here,
      objectives were to determine effects of low iCrit at birth on the adult
      endometrial transcriptome on pregnancy day (PxD) 13. On the first day of
      postnatal life, gilts were assigned to high or low iCrit groups. Adult high (n =
      8) and low (n = 7) iCrit gilts were bred (PxD 0), humanely slaughtered on PxD 13
      when tissues and fluids were collected. The endometrial transcriptome was defined
      for each group using mRNAseq and microRNAseq. Reads were mapped to the Sus scrofa
      11.1 genome build. Mature microRNAs were annotated using miRBase 21. Differential
      expression was defined based on fold change (>= +/- 1.5). Lactocrine deficiency
      did not affect corpora lutea number, uterine horn length, uterine wet weight,
      conceptus recovery, or uterine luminal fluid estrogen content on PxD 13. However,
      mRNAseq revealed 1157 differentially expressed endometrial mRNAs in high versus
      low iCrit gilts. Differentially expressed genes had functions related to solute
      transport, endometrial receptivity, and immune response. Six differentially
      expressed endometrial microRNAs included five predicted to target 62
      differentially expressed mRNAs, affecting similar biological processes. Thus,
      lactocrine deficiency on the first day of postnatal life can alter uterine
      developmental trajectory with lasting effects on endometrial responses to
      pregnancy as reflected at the level of the transcriptome on PxD 13.

PMID- 30107479
TI  - The Effect of Flow-Related Aneurysms on Hemorrhagic Risk of Intracranial
      Arteriovenous Malformations.
AB  - BACKGROUND: Previous reports indicated an association between hemorrhagic
      presentation and flow-related aneurysms in arteriovenous malformation (AVM)
      patients. However, it remains unclear whether these flow-related aneurysms result
      in the hemorrhage of AVM. OBJECTIVE: To characterize this hemorrhage risk using
      our institutional experience over 25 yr. METHODS: We retrospectively reviewed
      records of patients at our institution diagnosed with AVM from 1990 to 2015.
      Patients without associated aneurysms (AVM only) and those with flow-related
      aneurysms (AVM-FA) were compared. Those with intranidal or unrelated aneurysms
      were excluded. Annual risk of AVM-related hemorrhage was calculated using the
      birth-to-treatment approach and compared using Poisson rate ratio test. RESULTS:
      Among 526 patients, there were 457 AVM only patients and 69 with flow-related
      aneurysms. AVM-FA patients were older (P = .005). AVMs with flow-related
      aneurysms were more likely located in the cerebellar vermis and hemispheres (P =
      .023 and .001, respectively). Presence of flow-related aneurysms increased the
      risk of presentation with subarachnoid hemorrhage (P < .001). Interestingly, no
      significant differences in presenting hemorrhage due to AVM rupture were found (P
      > .356). The majority of aneurysms were untreated (69.5%), and only 8 (9.8%) had
      ruptured presentation. At follow-up (mean = 5.3 yr), patients with flow-related
      aneurysms were less likely to develop seizures (P = .004). The annual risk of AVM
      hemorrhage was 1.33% and 1.05% for AVM only patients and AVM-FA patients,
      respectively (P = .248). CONCLUSION: Despite increased risk of subarachnoid
      hemorrhage at presentation, there was no increased likelihood of rupture in AVMs
      with flow-related aneurysms. More studies are warranted, as clarifying the
      competing risks of AVM vs aneurysm rupture may be critical in determining optimal
      treatment strategy.

PMID- 30107480
TI  - A randomized controlled trial on the effect of lifestyle education for Iranian
      women and their husbands on post-partum anxiety and depression.
AB  - This randomized controlled trial was conducted on 189 pregnant women to determine
      the effect of lifestyle-based training for women and their husbands on post
      partum anxiety (PPA) and depression (PPD). Follow-ups were continued up for 6
      weeks after childbirth. Participants were allocated to three groups using block
      randomization. In the first intervention group, both the women and their
      husbands, and in the second intervention group only the women received the
      lifestyle-based education. In the control group, women received only routine
      care. Participants completed the Edinburgh Postnatal Depression Scale and
      Spielberger State-Trait Anxiety Inventory pre-intervention and 6 weeks after
      childbirth. When compared with the control group, significant reductions in PPD
      (adjusted difference: -5.5), state anxiety (-13.6) and trait anxiety (-12.6)
      scores were observed in the lifestyle education-dyad group, and also significant
      reductions in PPD (-3.2), state anxiety (-5.8) and trait anxiety (-4.9) scores
      were observed in the lifestyle education-women only group. Also, significant
      reductions were observed in PPD (-2.2), state anxiety (-7.8) and trait anxiety (
      7.7) scores in the lifestyle education-dyad group compared with the lifestyle
      education-women only group. Results showed the positive effect of lifestyle
      training on PPD and PPA, especially if the training is given to the parental
      dyad.

PMID- 30107481
TI  - Reply to Gauthier et al.

PMID- 30107482
TI  - Does abdominal obesity accelerate muscle strength decline in older adults?
      Evidence from the English Longitudinal Study of Ageing.
AB  - Background: Cross-sectional evidence has shown an association between abdominal
      obesity and lower muscle strength in older adults. However, no longitudinal
      findings have confirmed this association. In addition, the impact of abdominal
      fat on the reduction in muscle strength is not yet fully understood. Methods: We
      investigated the longitudinal associations between abdominal obesity and handgrip
      strength in 5,181 older adults from the English Longitudinal Study of Ageing
      (ELSA) over eight years of follow-up. Muscular strength was measured using a
      manual dynamometer. Abdominal obesity was defined as a waist circumference >102cm
      for men and >88cm for women. Generalized linear mixed models were adjusted by
      measures of socioeconomic status, health conditions, lifestyle, cognition,
      depressive symptoms, biomarkers and disability. Results: At baseline, the mean
      age of participants was 65.8 years and their mean waist circumference and BMI
      were 95 cm and 27.7 kg/m2, respectively. Fully adjusted models showed that
      abdominal obese men and women had stronger muscle strength at baseline. The
      decline over time in muscle strength was accelerated in abdominal obese men (
      0.12 kg per year, 95%CI = -0.24 - -0.01) compared to non-abdominal obese. This
      association was not found in women. Comparative analyses showed that overweight
      men according to their body mass index were not at greater risk of muscle
      strength decline. However, these men were at risk based on their waist
      circumference. Conclusions: Abdominal obesity is associated with accelerated
      muscle strength decline in men.

PMID- 30107483
TI  - Long sleep duration predicts a higher risk of obesity in adults: a meta-analysis
      of prospective cohort studies.
AB  - Background: The connections between long sleep duration and obesity or weight
      gain warrant further examination. This meta-analysis aimed to evaluate whether
      long sleep duration was associated with the risk of obesity, weight gain, body
      mass index (BMI) change or weight change in adults. Methods: PubMed, Embase,
      Cochrane Library, Elsevier Science Direct, Science Online, MEDLINE and CINAHL
      were searched for English articles published before May 2017. A total of 16
      cohort studies (n = 329 888 participants) from 8 countries were included in the
      analysis. Pooled relative risks (RR) or regression coefficients (beta) with 95%
      confidence intervals (CI) were estimated. Heterogeneity and publication bias were
      tested, and sensitivity analysis was also performed. Results: We found that long
      sleep duration was associated with higher risk of obesity (RR [95% CI] = 1.04
      [1.00-1.09], P = 0.037), but had no significant associations with weight gain,
      BMI change or weight change. Long sleep duration increased the risk of weight
      gain in three situations: among men, in studies with <5 years follow-up, and when
      sleep duration was 9 or more hours. Conclusions: Long sleep duration was
      associated with risk of obesity in adults. More cohort studies with objective
      measures are needed to confirm this relationship.

PMID- 30107484
TI  - Is the non-use of a saphenous vein graft the true question in coronary surgery?

PMID- 30107486
TI  - CD21 and FCRL5 form a receptor complex with robust B-cell activating capacity.
AB  - The B-cell response to antigen is critically regulated by co-receptors. CD21
      (complement receptor 2) amplifies the response to antigen linked to its ligands,
      specific C3 fragments. In contrast, human Fc receptor-like 5 (FCRL5), a novel IgG
      receptor, was reported to inhibit B-cell receptor (BCR) signaling. Here, we show
      that CD21 and FCRL5 physically associate, suggesting that immune complexes
      containing both C3 fragment and IgG could simultaneously engage the pre-assembled
      receptors. We found that activating signaling molecules such as CD19, active
      PLCgamma2 and BTK were rapidly recruited to FCRL5 upon engagement, suggesting a
      novel activating function for FCRL5. We confirmed that FCRL5 through its ITIMs
      (immunoreceptor tyrosine-based inhibitory motif) inhibited BCR signaling in the
      absence of CD21 stimulation. In contrast, triple engagement of FCRL5, CD21 and
      the BCR led to a superior calcium response compared to CD21 and BCR co
      stimulation, in both cell lines and tonsil B cells. Furthermore, the novel
      activating function was independent of established FCRL5 signaling motifs. While
      human peripheral B cells express either FCRL5 or CD21, we identified a sizable
      subset of tonsil B cells which co-express the two receptors. We propose that
      FCRL5 has dual signaling capacity, while CD21 co-engagement serves as molecular
      switch, converting FCRL5 from a negative to a positive co-receptor. In tissues, B
      cells that co-express FCRL5 and CD21 could robustly respond to IgG immune
      complexes loaded with C3 fragments.

PMID- 30107487
TI  - Structural Validity of the Short Musculoskeletal Function Assessment in Patients
      With Injuries.
AB  - Background: The Short Musculoskeletal Function Assessment (SMFA) is a widely used
      patient-reported outcome measure, originally having 2 elements of outcome: the
      function index and the bother index. In multiple studies, it has been argued that
      the SMFA should be scored using 3, 4, or 6 subscales instead. Therefore, there is
      inconsistency with the number of underlying dimensions of the SMFA. Objective:
      The aim of this study was to evaluate the structural validity of the various
      proposed subscale configurations of the SMFA in a broad range of Dutch patients
      with injuries. Design: This study used a prospective cohort design. Methods:
      Participants with injuries were asked to complete the Dutch SMFA (SMFA-NL) at 5
      to 8 weeks postinjury. The structural validity of the 6 different factor
      structures that have been proposed in other studies was evaluated using
      confirmatory factor analyses. Internal consistency was analyzed using Cronbach
      alpha. Results: A total of 491 patients participated (response rate = 74%). A 4
      factor structure showed an acceptable fit (root-mean-square error of
      approximation [RMSEA] = 0.070, comparative fit index = 0.973, Tucker-Lewis index
      = 0.971). Other models, including the original 2-index structure, showed
      insufficient structural validity in Dutch patients with injuries. The 4-factor
      structure showed sufficient discriminant validity and good internal consistency
      (Cronbach alpha >= 0.83). Limitations: It is unclear whether conclusions are
      generalizable across different countries, people who are elderly, and people
      without injuries. Conclusion: In a broad range of patients with injuries, the
      SMFA-NL may be best scored and interpreted using a 4-factor structure. Other
      factor structures showed insufficient structural validity.

PMID- 30107485
TI  - High Cure Rates With Grazoprevir-Elbasvir With or Without Ribavirin Guided by
      Genotypic Resistance Testing Among Human Immunodeficiency Virus/Hepatitis C Virus
      coinfected Men Who Have Sex With Men.
AB  - Background: This study was performed to investigate the efficacy and safety of
      grazoprevir-elbasvir guided by baseline resistance-associated substitutions
      (RASs) in the Swiss HCVree Trial (clinicaltrials.gov NCT02785666). Methods: We
      performed hepatitis C virus (HCV) RNA screening among all men who have sex with
      men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating
      HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment.
      Genotype 1a-infected individuals with baseline RASs and genotype 4-infected
      individuals with prior failure of HCV treatment received 16 weeks of grazoprevir
      elbasvir combined with ribavirin. All other individuals received 12 weeks of
      grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional
      partners were offered a HCV risk reduction-oriented behavioral intervention.
      Results: We screened 3722 MSM and identified 177 (4.8%) with replicating
      infection. A total of 122 individuals (3.3%) were eligible for study treatment.
      Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs.
      Sustained virological response after 12 weeks of follow-up was achieved in 121
      patients (99%), including all with genotype 1a infection. Overall, 8 serious
      adverse events occurred, none of which was related to the study drug. Seventy
      five percent of eligible MSM participated in the risk counseling program.
      Conclusions: Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin,
      achieved high cure rates and had an excellent safety profile. Unique to other
      studies, the treatment duration was guided by the presence of baseline RASs among
      genotype 1a-infected individuals, and the treatment phase was accompanied by an
      HCV risk reduction-oriented behavioral intervention. This successful population
      wide treatment approach lays the groundwork to achieve HCV elimination in
      coinfected MSM.

PMID- 30107488
TI  - Dairy matrix effects: response to consumption of dairy fat differs when eaten
      within the cheese matrix-a randomized controlled trial.
AB  - Background: Dairy fat consumed as cheese has different effects on blood lipids
      than that consumed as butter. It is unknown whether the effect is specific to fat
      interaction with other cheese nutrients (calcium, casein proteins), or to the
      cheese matrix itself. Objective: We aimed to test the effect of 6 wk daily
      consumption of ~40 g dairy fat, eaten within macronutrient-matched food matrices,
      on markers of metabolic health, in overweight adults aged >=50 y. Design: The
      study was a 6-wk randomized parallel intervention; 164 volunteers (75 men)
      received ~40 g of dairy fat/d, in 1 of 4 treatments: (A) 120 g full-fat Irish
      cheddar cheese (FFCC) (n = 46); (B) 120 g reduced-fat Irish cheddar cheese +
      butter (21 g) (RFC + B) (n = 45); (C) butter (49 g), calcium caseinate powder (30
      g), and Ca supplement (CaCO3) (500 mg) (BCC) (n = 42); or (D) 120 g FFCC, for 6
      wk (as per A) (n = 31). Group D first completed a 6-wk "run-in" period, where
      they excluded all dietary cheese before commencing the intervention. Results:
      There was no difference in anthropometry, fasting glucose, or insulin between the
      groups at pre- or postintervention. However, a stepwise-matrix effect was
      observed between the groups for total cholesterol (TC) (P = 0.033) and LDL
      cholesterol (P = 0.026), with significantly lower postintervention TC (mean +/-
      SD) (5.23 +/- 0.88 mmol/L) and LDL cholesterol (2.97 +/- 0.67 mmol/L) when all of
      the fat was contained within the cheese matrix (Group A), compared with Group C
      when it was not (TC: 5.57 +/- 0.86 mmol/L; LDL cholesterol: 3.43 +/- 0.78
      mmol/L). Conclusion: Dairy fat, eaten in the form of cheese, appears to
      differently affect blood lipids compared with the same constituents eaten in
      different matrices, with significantly lower total cholesterol observed when all
      nutrients are consumed within a cheese matrix This trial was registered at ISRCTN
      as ISRCTN86731958.

PMID- 30107489
TI  - Reduction in mortality from implantable cardioverter-defibrillators in non
      ischaemic cardiomyopathy patients is dependent on the presence of left
      ventricular scar.
AB  - Aims: In patients with non-ischaemic cardiomyopathy (NICM), the mortality benefit
      of a primary prevention implantable cardioverter-defibrillator (ICD) has been
      challenged. Left ventricular (LV) scar identified by cardiac magnetic resonance
      (CMR) imaging is associated with a high risk of malignant arrhythmia in NICM. We
      aimed to determine the impact of LV scar on the mortality benefit from a primary
      prevention ICD in NICM. Methods and results: We recruited 452 consecutive heart
      failure patients [New York Heart Association (NYHA) Class II/III] with NICM and
      LV ejection fraction <=35% from a state-wide CMR service. All patients fulfilled
      European Society of Cardiology guidelines for primary prevention ICD
      implantation; however, the decision to implant was at the treating physician's
      discretion. Baseline clinical and CMR data were recorded prospectively and heart
      failure mortality risk (MAGGIC score) was calculated. The primary study outcome
      measurement was all-cause mortality based on presence or absence of ICD,
      stratified by LV scar. Median follow-up was 37.9 months and there was no
      difference in MAGGIC score between those who did and did not receive a primary
      prevention ICD (19.30 +/- 5.46 vs. 18.90 +/- 5.67, P = 0.50). In patients without
      LV scar, ICD implantation was not associated with improved mortality [hazard
      ratio (HR) = 1.22, 95% confidence interval (CI): 0.53-2.78, P = 0.64]. In
      patients with LV scar, ICD implantation was independently associated with reduced
      mortality (HR = 0.45, 95% CI: 0.26-0.77, P = 0.003). Conclusions: In patients
      with NICM, primary prevention ICD implantation is only associated with reduced
      mortality in patients with LV scar. This may enable more effective selection of
      NICM patients for ICD implantation compared with current guidelines.

PMID- 30107491
TI  - Carbapenemases in New York City: the continued decline of KPC-producing
      Klebsiella pneumoniae, but a new threat emerges.
AB  - Objectives: Carbapenemase-producing Enterobacteriaceae are important nosocomial
      pathogens in many medical centres. Surveillance is needed to track trends and
      detect emergence of new carbapenemases. Methods: Single-patient isolates of
      Enterobacteriaceae were gathered from seven medical centres in New York City over
      a 3 month period in 2017. Susceptibility testing was performed and isolates were
      screened for selected carbapenemases. Additional isolates referred to our
      laboratory in 2018 were also tested. Results: KPC was found in 3/1911 (0.16%)
      isolates of Escherichia coli, 22/533 (4.1%) isolates of Klebsiella pneumoniae and
      3/175 (1.7%) isolates of Enterobacter spp. Compared with prior surveillance
      studies performed over the past decade, there has been a persistent decline in
      the number of KPC-possessing K. pneumoniae. However, in 2018 two patients from
      the same skilled nursing facility admitted to two separate hospitals were found
      to harbour Enterobacteriaceae with NDM-5 and CTX-M-15. Conclusions: Since the
      height of the outbreak in 2006, there has been a decline in the number of KPC
      possessing Enterobacteriaceae in New York City acute care medical centres.
      However continued vigilance is needed to detect the emergence of other
      carbapenemases.

PMID- 30107490
TI  - The Metabolic Syndrome Does Not Affect Development of Collateral Circulation in
      the Poststenotic Swine Kidney.
AB  - BACKGROUND: The collateral circulation is important in maintenance of blood
      supply to the ischemic kidney distal to renal artery stenosis (RAS). Obesity
      metabolic syndrome (MetS) preserves renal blood flow (RBF) in the stenotic
      kidney, but whether this is related to an increase of collateral vessel growth is
      unknown. We hypothesized that MetS increased collateral circulation around the
      renal artery. METHODS: Twenty-one domestic pigs were randomly divided into
      unilateral RAS fed an atherogenic (high-fat/high-fructose, MetS-RAS) or standard
      diet, or controls (n = 7 each). RBF, glomerular filtration rate (GFR), and the
      peristenotic collateral circulation were assessed after 10 weeks using
      multidetector computed tomography (CT) and the intrarenal microcirculation by
      micro-CT. Vascular endothelial growth factor (VEGF) expression was studied in the
      renal artery wall, kidney, and perirenal fat. Renal fibrosis and stiffness were
      examined by trichrome and magnetic resonance elastography. RESULTS: Compared with
      controls, RBF and GFR were decreased in RAS, but not in MetS-RAS. MetS-RAS formed
      peristenotic collaterals to the same extent as RAS pigs but induced greater
      intrarenal microvascular loss, fibrosis, stiffness, and inflammation. MetS-RAS
      also attenuated VEGF expression in the renal tissue compared with RAS, despite
      increased expression in the perirenal fat. CONCLUSIONS: MetS does not interfere
      with collateral vessel formation in the stenotic kidney, possibly because
      decreased renal arterial VEGF expression offsets its upregulation in perirenal
      fat, arguing against a major contribution of the collateral circulation to
      preserve renal function in MetS-RAS. Furthermore, preserved renal function does
      not protect the poststenotic kidney from parenchymal injury.

PMID- 30107493
TI  - Facelift Performed Safely Under Local Anesthesia With Oral Sedation: Analysis of
      174 Patients.
AB  - Background: Anesthesia for elective ambulatory procedures must provide
      appropriate pain control while minimizing perioperative risk. Local anesthesia in
      combination with oral sedation provides a safe office-based method of anesthesia
      for rhytidectomy. Objectives: The purpose of this analysis was to identify the
      incidence of traditional outcome parameters in ambulatory rhytidectomy performed
      with local anesthesia and oral sedation. Methods: A retrospective chart review
      was performed on all patients who underwent office-based rhytidectomy under local
      anesthesia with oral sedation from February 2011 to May 2017. A total of 174
      patients were included. The data collected included patient medical and surgical
      history, medications, body mass index, tobacco use history, operative time,
      technique, and concurrent procedures. All intraoperative and postoperative
      complications were recorded. Results: One hundred and sixty-five patients were
      female (94.8%) and nine were male (5.2%) with a mean age of 57.6 years (SD +/-
      7.90). There were 46 complications, including 23 hematomas (13.2%), six seromas,
      six episodes of emesis, five infections, four scar deformities, and two ear
      deformities. Of the 23 hematomas, only two hematomas required operative
      evacuation with local anesthesia in the office procedure room. Twenty-one
      hematomas were small and managed with percutaneous needle aspiration, followed by
      surveillance. The five infections resolved after oral antibiotics only. There
      were no thromboembolic events or hospitalizations. Conclusion: The use of only
      local anesthesia in combination with oral sedation safely permits the performance
      of rhytidectomy with similar incidence of rhytidectomy-related complications
      without the risk related to general anesthesia.

PMID- 30107492
TI  - Measurement of Central Aortic Blood Pressure in Youth: Role of Obesity and Sex.
AB  - BACKGROUND: The relationship between pediatric severe obesity (SO) and central
      aortic blood pressure (BP) has yet to be established. METHODS: We conducted a
      cross-sectional study of 348 youth (48.5% male, age 12.7 +/- 0.1 years) with a
      wide range of body mass index (BMI) values: normal weight (NW; >=5th and <85th
      BMI percentiles), overweight/obesity (OW/OB; 85th to <120% of the 95th BMI
      percentile), and SO (>=120% of the 95th BMI percentile). Measures of central
      aortic BP were obtained via applanation tonometry with SphygmoCor MM3 software.
      RESULTS: After adjustment for covariates, no significant sex differences were
      observed for radial-aortic systolic blood pressure (SBP) (P = 0.39), carotid
      aortic SBP (P = 0.99), radial-aortic diastolic blood pressure (DBP) (P = 0.44),
      and carotid-aortic DBP (P = 0.53). Compared to youth with NW, youth with SO
      exhibited higher radial-aortic SBP (SO vs. NW: 102 +/- 1 mm Hg vs. 90 +/- 1 mm
      Hg, P<0.001), carotid-aortic SBP (SO vs. NW: 121 +/- 1 mm Hg vs. 109 +/- 1 mm Hg,
      P<0.001), and carotid-aortic DBP (SO vs. NW: 60 +/- 1 mm Hg vs. 56 +/- 1 mm Hg, P
      = 0.04). Compared to youth with OW/OB, youth with SO had higher radial-aortic SBP
      (OW/OB: 97 +/- 1 mm Hg, P = 0.002) and carotid-aortic SBP (OW/OB: 114 +/- 1 mm
      Hg, P = 0.007). After adjusting for either total-body percent fat mass or
      visceral adipose tissue, BMI was still a significant predictor of both radial
      aortic and carotid-aortic SBP and DBP (P<0.001, all). CONCLUSIONS: In a cohort of
      youth with a wide range of adiposity levels, central aortic BP was elevated among
      individuals with SO and associated with BMI but not body fatness.

PMID- 30107494
TI  - High Number of Potential Transmitters Revealed in a Population-based Systematic
      Hepatitis C Virus RNA Screening Among Human Immunodeficiency Virus-infected Men
      Who Have Sex With Men.
AB  - Background: The proportion of undiagnosed hepatitis C virus (HCV) infections in
      high-risk populations, such as human immunodeficiency virus (HIV)-infected men
      who have sex with men (MSM) is unclear. Identification of potential HCV
      transmitters is important to reach World Health Organization HCV elimination
      targets. Methods: Between October 2015 and May 2016, we performed a systematic
      HCV RNA-based screening among HIV-infected MSM participating in the Swiss HIV
      Cohort Study (SHCS). HCV antibodies were measured from all HCV RNA-positive
      samples. Results: Of 4257 MSM recorded in the SHCS database, we screened 3722
      (87%) by HCV polymerase chain reaction, and 177 (4.8%) harbored a replicating HCV
      infection. We identified 24 individuals (14%) with incident HCV infection; one
      third of them had a negative HCV antibody result at the time of HCV RNA
      positivity. In a multivariable model, elevated liver enzyme values (odds ratio,
      14.52; 95% confidence interval, 9.92-21.26), unprotected sex with occasional
      partners (2.01; 1.36-2.98), intravenous drug use (7.13; 4.36-11.64),
      noninjectable drug use (1.94; 1.3-2.88), and previous syphilis diagnosis (2.56;
      1.74-3.76) were associated with HCV RNA positivity. Conclusions: A systematic HCV
      RNA-based screening among HIV-infected MSM revealed a high number of potential
      transmitters. A substantial subpopulation of MSM had incident infection, one
      third of whom had a negative HCV antibody test result at the time of the HCV RNA
      positivity. These data reveal that one-time RNA testing of a high-risk population
      for HCV RNA might identify more infected persons than routine testing for HCV
      antibodies and liver enzymes.

PMID- 30107496
TI  - Metabolic engineering strategies for improvement of ethanol production in
      cellulolytic Saccharomyces cerevisiae.
AB  - As a traditional ethanol-producing microorganism, Saccharomyces cerevisiae is an
      ideal host for consolidated bioprocessing. However, expression of heterologous
      cellulase increases the metabolic burden in yeast, which results in low cellulase
      activity and poor cellulose degradation efficiency. In this study, cellulase
      expressing yeast strains that could efficiently degrade different cellulosic
      substrates were created by optimizing cellulase ratios through a POT1-mediated
      delta-integration strategy. Metabolic engineering strategies, including
      optimization of codon usage, promoter and signal peptide, were also included in
      this system. We also confirmed that heterologous cellulase expression in
      cellulosic yeast induced the unfolded protein response. To enhance protein
      folding capacity, the endoplasmic reticulum chaperone protein BiP and the
      disulfide isomerase Pdi1p were overexpressed, and the Golgi membrane protein
      Ca2+/Mn2+ ATPase Pmr1p was disrupted to decrease the glycosylation of cellulase.
      The resultant strain, SK18-3, could produce 5.4 g L-1 ethanol with carboxymethyl
      cellulose. Strain SK12-50 achieved 4.7 g L-1 ethanol production with phosphoric
      acid swollen cellulose hydrolysis. When Avicel was used as the substrate, 3.8 g L
      1 ethanol (75% of the theoretical maximum yield) was produced in SK13-34. This
      work will significantly increase our knowledge of how to engineer optimal yeast
      strains for biofuel production from cellulosic biomass.

PMID- 30107495
TI  - Structural basis for the synergy of 4'- and 2'-modifications on siRNA nuclease
      resistance, thermal stability and RNAi activity.
AB  - Chemical modification is a prerequisite of oligonucleotide therapeutics for
      improved metabolic stability, uptake and activity, irrespective of their mode of
      action, i.e. antisense, RNAi or aptamer. Phosphate moiety and ribose C2'/O2'
      atoms are the most common sites for modification. Compared to 2'-O-substituents,
      ribose 4'-C-substituents lie in proximity of both the 3'- and 5'-adjacent
      phosphates. To investigate potentially beneficial effects on nuclease resistance
      we combined 2'-F and 2'-OMe with 4'-Calpha- and 4'-Cbeta-OMe, and 2'-F with 4'
      Calpha-methyl modification. The alpha- and beta-epimers of 4'-C-OMe-uridine and
      the alpha-epimer of 4'-C-Me-uridine monomers were synthesized and incorporated
      into siRNAs. The 4'alpha-epimers affect thermal stability only minimally and show
      increased nuclease stability irrespective of the 2'-substituent (H, F, OMe). The
      4'beta-epimers are strongly destabilizing, but afford complete resistance against
      an exonuclease with the phosphate or phosphorothioate backbones. Crystal
      structures of RNA octamers containing 2'-F,4'-Calpha-OMe-U, 2'-F,4'-Cbeta-OMe-U,
      2'-OMe,4'-Calpha-OMe-U, 2'-OMe,4'-Cbeta-OMe-U or 2'-F,4'-Calpha-Me-U help
      rationalize these observations and point to steric and electrostatic origins of
      the unprecedented nuclease resistance seen with the chain-inverted 4'beta-U
      epimer. We used structural models of human Argonaute 2 in complex with guide
      siRNA featuring 2'-F,4'-Calpha-OMe-U or 2'-F,4'-Cbeta-OMe-U at various sites in
      the seed region to interpret in vitro activities of siRNAs with the corresponding
      2'-/4'-C-modifications.

PMID- 30107497
TI  - Immune checkpoint inhibitors myocarditis: not all cases are clinically patent.

PMID- 30107498
TI  - Southern South Australian groundwater microbe diversity.
AB  - Groundwater is increasingly used globally for domestic, industrial and
      agricultural production. While many studies have focused on groundwater as a
      resource, the diverse ecosystems within are often ignored. Here, we assess 54
      Southern South Australian groundwater microbial communities from the populated
      part of the state to assess their status and dynamics in isolated groundwater
      systems. We observed a strong site-to-site individuality in groundwater bacterial
      communities, likely due to the isolated nature of groundwater bodies leading to
      unique ecosystems. Rank abundance analysis indicates bacterial diversity is
      maintained even at low abundances and that the distribution fits classical
      ecological models for strong competition in resource-limited environments.
      Combined, our data indicates that despite overrepresentation of pollutant
      associated bacterial orders in and around the Adelaide metropolitan area,
      microbial communities remain diverse and show little evidence of converging on a
      common pollutant-effected community.

PMID- 30107499
TI  - Interictal stereotactic-EEG functional connectivity in refractory focal
      epilepsies.
AB  - Drug-refractory focal epilepsies are network diseases associated with functional
      connectivity alterations both during ictal and interictal periods. A large
      majority of studies on the interictal/resting state have focused on functional
      MRI-based functional connectivity. Few studies have used electrophysiology,
      despite its high temporal capacities. In particular, stereotactic-EEG is highly
      suitable to study functional connectivity because it permits direct intracranial
      electrophysiological recordings with relative large-scale sampling. Most previous
      studies in stereotactic-EEG have been directed towards temporal lobe epilepsy,
      which does not represent the whole spectrum of drug-refractory epilepsies. The
      present study aims at filling this gap, investigating interictal functional
      connectivity alterations behind cortical epileptic organization and its
      association with post-surgical prognosis. To this purpose, we studied a large
      cohort of 59 patients with malformation of cortical development explored by
      stereotactic-EEG with a wide spatial sampling (76 distinct brain areas were
      recorded, median of 13.2 per patient). We computed functional connectivity using
      non-linear correlation. We focused on three zones defined by stereotactic-EEG
      ictal activity: the epileptogenic zone, the propagation zone and the non-involved
      zone. First, we compared within-zone and between-zones functional connectivity.
      Second, we analysed the directionality of functional connectivity between these
      zones. Third, we measured the associations between functional connectivity
      measures and clinical variables, especially post-surgical prognosis. Our study
      confirms that functional connectivity differs according to the zone under
      investigation. We found: (i) a gradual decrease of the within-zone functional
      connectivity with higher values for epileptogenic zone and propagation zone, and
      lower for non-involved zones; (ii) preferential coupling between structures of
      the epileptogenic zone; (iii) preferential coupling between epileptogenic zone
      and propagation zone; and (iv) poorer post-surgical outcome in patients with
      higher functional connectivity of non-involved zone (within- non-involved zone,
      between non-involved zone and propagation zone functional connectivity). Our work
      suggests that, even during the interictal state, functional connectivity is
      reinforced within epileptic cortices (epileptogenic zone and propagation zone)
      with a gradual organization. Moreover, larger functional connectivity
      alterations, suggesting more diffuse disease, are associated with poorer post
      surgical prognosis. This is consistent with computational studies suggesting that
      connectivity is crucial in order to model the spatiotemporal dynamics of
      seizures.10.1093/brain/awy214_video1awy214media15833456182001.

PMID- 30107500
TI  - Cohort profile: The Boston Hospital Workers Health Study (BHWHS).

PMID- 30107502
TI  - Scholarly reputation.
AB  - The aim of this literature review on scholarly reputation is: (i) to clarify the
      concept of scholarly reputation; and (ii) to identify the opportunities for
      scholars (and especially the early career ones among them) to build, maintain and
      showcase their reputation in today's increasingly open-values based, digital and
      networked environment. Thus, an in-depth discussion of the notion of scholarly
      reputation, inclusive of its multi-dimensional sub-constructs and antecedents, is
      followed by an attempt to establish how it is to be achieved and managed.

PMID- 30107501
TI  - Motor and emotional behaviours elicited by electrical stimulation of the human
      cingulate cortex.
AB  - The cingulate cortex is a mosaic of different anatomical fields, whose functional
      characterization is still a matter of debate. In humans, one method that may
      provide useful insights on the role of the different cingulate regions, and to
      tackle the issue of the functional differences between its anterior, middle and
      posterior subsectors, is intracortical electrical stimulation. While previous
      reports showed that a variety of integrated behaviours could be elicited by
      stimulating the midcingulate cortex, little is known about the effects of the
      electrical stimulation of anterior and posterior cingulate regions. Moreover, the
      internal arrangement of different behaviours within the midcingulate cortex is
      still unknown. In the present study, we extended previous stimulation studies by
      retrospectively analysing all the clinical manifestations induced by
      intracerebral high frequency electrical stimulation (50 Hz, pulse width: 1 ms, 5
      s, current intensity: average intensity of 2.7 +/- 0.7 mA, biphasic) of the
      entire cingulate cortex in a cohort of 329 drug-resistant epileptic patients
      (1789 stimulation sites) undergoing stereo-electroencephalography for a
      presurgical evaluation. The large number of patients, on one hand, and the
      accurate multimodal image-based localization of stereo-electroencephalography
      electrodes, on the other hand, allowed us to assign specific functional
      properties to modern anatomical subdivisions of the cingulate cortex. Behavioural
      or subjective responses were elicited from the 32.3% of all cingulate sites,
      mainly located in the pregenual and midcingulate regions. We found clear
      functional differences between the pregenual part of the cingulate cortex,
      hosting the majority of emotional, interoceptive and autonomic responses, and the
      anterior midcingulate sector, controlling the majority of all complex motor
      behaviours. Particularly interesting was the 'actotopic' organization of the
      anterior midcingulate sector, arranged along the ventro-dorsal axis: (i) whole
      body behaviours directed to the extra-personal space, such as getting-up
      impulses, were elicited ventrally, close to the corpus callosum; (ii) hand
      actions in the peripersonal space were evoked by the stimulation of the
      intermediate position; and (iii) body-directed actions were induced by the
      stimulation of the dorsal branch of the cingulate sulcus. The caudal part of the
      midcingulate cortex and the posterior cingulate cortex were, in contrast, poorly
      excitable, and mainly devoted to sensory modalities. In particular, the caudal
      part of the midcingulate cortex hosted the majority of vestibular responses,
      while posterior cingulate cortex was the principal recipient of visual effects.
      We will discuss our data in the light of current controversies on the role of the
      cingulate cortex in cognition and emotion.

PMID- 30107503
TI  - Plasma indoleamine 2,3-dioxygenase activity is associated with the size of HIV
      reservoir in patients receiving antiretroviral therapy.
AB  - Background: Indoleamine 2, 3-dioxygenase (IDO) is an immunoregulatory enzyme that
      metabolises tryptophan to immunosuppressive kynurenines. We investigated whether
      IDO activity is associated with the size of HIV reservoirs. Methods: In this
      cross-sectional study, total HIV DNA in PBMCs from 127 HIV-infected patients
      receiving antiretroviral therapy (ART) was quantified. Tryptophan and kynurenine
      concentrations, as well as microbial translocation markers were measured in
      plasma samples. T cell activation (HLA-DR, CD38) and exhaustion (programmed cell
      death-1 (PD-1)) in PBMC were assessed by flow cytometry. Results: Elevated IDO
      activity prior to ART correlated with on-ART HIV DNA (r=0.35, P=0.004), but was
      not associated with pre-ART HIV DNA. A median duration of 15 months of ART
      significantly decreased IDO activity from the pre-ART levels; however, these
      levels were still higher than those observed in HIV-uninfected controls. Among
      treated participants, IDO activity positively correlated with their concurrent
      HIV DNA (r=0.36, P<0.0001). Multivariate model showed an independent association
      of pre-ART CD4/CD8 ratio (adjusted Odds ratio (aOR) =0.75 per 0.1 increase, 95%
      confidential intervals (CI): 0.62-0.91) and on-ART IDO activity (aOR=1.09 per
      nM/MUM increase, 95%CI: 1.04-1.14) with higher levels of HIV DNA on-ART. A lack
      of association of the microbial translocation markers was observed with the size
      of HIV reservoir. Among treated participants, HIV DNA positively correlated with
      the proportions of activated CD4 T and CD8 T cells and exhausted CD4 T cells.
      Conclusions: We observed a positive correlation between IDO activity and total
      HIV DNA in blood, highlighting the important role of immunometabolic aberrations
      in HIV persistence.

PMID- 30107505
TI  - Climate-woodland effects on population genetics for two congeneric lichens with
      contrasting reproductive strategies.
AB  - Genetic variation is expected to be influenced by the interaction between
      reproductive mode and dispersal traits on the one hand and environmental and
      habitat setting affecting establishment success on the other. We evaluated how
      environmental/habitat setting affects population genetic variation (i.e.
      variation in genetic diversity and structure) when regulated by contrasting
      dispersal traits. We used fungus-specific microsatellite markers to examine
      genetic diversity and structure of two closely related epiphytic lichen fungi
      that differ in their primary reproductive mode: Nephroma laevigatum (sexually
      reproducing, n = 191, 10 microsatellites) and N. parile (asexually reproducing, n
      = 182, 12 microsatellites), along a steep climatic gradient in Scotland. Despite
      their reproductive differences, we found a high proportion of clones in both
      species and a background pattern of genetic structure related to climatic
      gradients. We also demonstrated that woodland connectivity, rather than
      geographic distance, explained genetic diversity in both species.
      Environmental/habitat setting, modulated by the reproductive mode of the species,
      affects genetic diversity and structure, but the putative dissimilarity in their
      reproductive mode is less important than has been previously assumed. We
      reinforce the importance of protecting highly connected populations, positioned
      along a gradient capturing the segregation of gene pool differences in response
      to climatic variation.

PMID- 30107504
TI  - Laboratory-acquired scrub typhus and murine typhus infections: The argument for
      risk-based approach to biosafety requirements for Orientia tsutsugamushi and
      Rickettsia typhi laboratory activities.
AB  - This study examined the literature on laboratory-acquired infections (LAIs)
      associated with scrub typhus (Orientia tsutsugamushi) and murine typhus
      (Rickettsia typhi) research to provide an evidence base for biosafety and
      biocontainment. Scrub typhus LAIs were documented in 25 individuals, from 1931
      2000 with 8 (32%) deaths during the pre-antibiotic era. There were 35 murine
      typhus LAI reports and no deaths. Results indicated that highest risk activities
      were working with infectious laboratory animals involving significant aerosol
      exposures, accidental self-inoculation or bite related infections. A risk-based
      biosafety approach for in vitro and in vivo culture of O. tsutsugamushi and R.
      typhi would require only high-risk activities (animal work or large culture
      volumes) be performed in high containment BSL3 laboratories. We argue that
      relatively low risk activities including inoculation of cell cultures or the
      early stages of in vitro growth using low volumes/low concentrations of
      infectious materials can be performed safely in BSL2 laboratories within a
      biological safety cabinet.

PMID- 30107506
TI  - Relative bioavailability of phosphorus in high-protein sunflower meal for broiler
      chickens and effects of dietary phytase supplementation on bone traits, growth
      performance, and apparent ileal digestibility of nutrients.
AB  - An experiment was conducted to determine the relative bioavailability (RBV) of P
      in high-protein sunflower meal (HP-SFM) fed to broiler chickens based on bone
      traits and to determine the effects of dietary phytase supplementation and
      increasing levels of HP-SFM as a P source on bone traits, growth performance, and
      apparent ileal digestibility (AID) of DM and nutrients. In total, 240 broiler
      chicks were randomly allotted to 1 of 10 experimental diets with 6 replicate
      cages of 4 birds each and fed experimental diets from day 14 to 21 of age. Diets
      included a corn-soybean meal-based basal diet (0.35% total P; P-deficient diet),
      or the basal diet supplemented with 0.05, 0.10, or 0.15% P from either monosodium
      phosphate (MSP) or HP-SFM. Another 3 diets were formulated by supplementing the
      HP-SFM-containing diets with 500 phytase unit/kg of phytase. The bone mineral
      content (BMC), bone area (BA), and bone mineral density (BMD) of femur and tibia
      and tibia ash content increased (linear, P < 0.01) with increasing dietary P
      content from MSP. A linear increase in femur and tibia BMC, femur BA, and tibia
      BMD was also observed (P < 0.01) with increasing level of dietary P from HP-SFM.
      The RBV of P in HP-SFM based on femur and tibia BMC were 41 and 44%,
      respectively. Dietary phytase supplementation increased (P < 0.01) most of bone
      traits of the birds except for femur BMD. In addition, birds fed the diets
      supplemented with dietary phytase had greater (P < 0.05) BW gain, feed
      efficiency, and AID of P than those fed the diets without dietary phytase. In
      conclusion, the estimated RBV of P in HP-SFM to P in MSP were 41 and 44% based on
      femur and tibia BMC, respectively. Also, dietary phytase supplementation
      increased AID of P, growth performance, and bone traits of the birds fed P
      deficient diets containing increasing inclusion level of HP-SFM as a P source.

PMID- 30107507
TI  - Sexually Dimorphic Eye-Loss Driven by Ecological Selection in an Ostracod
      Crustacean: Support for the Reproductive Role Hypothesis.
AB  - Euphilomedes carcharodonta ostracods exhibit sex-specific eye-loss, with females
      lacking image-forming compound eyes compared with males and related species. The
      standard assumption is that sexual dimorphism is driven by sexual selection.
      However, previous work in E. carcharodonta suggests that male eyes are used to
      evade predators in the male-specific ecological niche, and that male-eyes lack
      the resolution to search for females. In this study, we examine whether sexual
      selection or ecological selection drives the retention of male eyes. Ecological
      niche differentiation was hypothesized by Darwin (1871) to be an alternative
      selective force for sexual dimorphism either through food competition or through
      dimorphic sex-role behavior, the reproductive role hypothesis. As of yet, there
      is little experimental evidence supporting this hypothesis. Here, we
      experimentally blindfold male E. carcharodonta to mimic the female phenotype and
      examine the effects on sex-specific niches and behavior. Blindfolding does not
      appear to grossly change male behavior, nor do females behave differently when
      exposed to blindfolded males. This lead us to conclude that the development of
      complex eyes in male E. arises from ecological selection rather than sexual
      selection.

PMID- 30107508
TI  - Corrigendum to "Development and application of a SYBR green real-time PCR for
      detection of the emerging avian leukosis subgroup K".

PMID- 30107509
TI  - Comparison of mitral valve geometrical effect of percutaneous edge-to-edge repair
      between central and eccentric functional mitral regurgitation: clinical
      implications.
AB  - Aims: Percutaneous edge-to-edge repair alters mitral valve (MV) geometry in
      functional mitral regurgitation (FMR). We sought to characterize MV morphology in
      patients with central and eccentric FMR, compare the geometrical effect of
      MitraClip therapy, and elucidate different mechanisms of MR improvement according
      to FMR subtypes. Methods and results: Seventy-six symptomatic patients with Grade
      3 to 4+ FMR (central, n = 39; eccentric, n = 37) underwent three-dimensional
      transoesophageal echocardiography during MitraClip implantation. We defined
      procedural success as a reduction of MR by >=1 grade with having a residual
      mitral regurgitation (MR) of <= grade 2+. Procedural success rate was similar
      between central and eccentric FMR (77% vs. 78%, P = 0.55). After MitraClip, the
      reduction in anterior-posterior diameter did not differ between FMR subtypes, but
      patients with eccentric FMR had a greater reduction in the averaged tethering
      angle difference (P < 0.001) with less reduction in tenting volume and height
      (both P < 0.001) than did patients with central FMR. On multivariable analysis,
      in central FMR, MR reduction post-clip was associated with shortening in anterior
      posterior diameter [coefficient 0.388, 95% confidence interval (CI) 0.216-0.561;
      P < 0.001] and an increase in coaptation area (coefficient 0.117, 95% CI 0.039
      0.194; P = 0.004), whereas in eccentric FMR MR reduction was mainly associated
      with a decrease in the averaged tethering angle difference (coefficient 0.050,
      95% CI 0.021-0.078; P = 0.001). Conclusion: MV geometrical effect and its
      association with MR improvement after MitraClip therapy differ according to FMR
      subtypes. Our results indicate the MR jet direction and the leaflet tethering
      pattern may be considered in the strategy for percutaneous treatment for FMR.

PMID- 30107510
TI  - Host plant adaptation in cactophilic species of the Drosophila buzzatii cluster:
      fitness and transcriptomics.
AB  - Host plant shifts in herbivorous insects often involve facing new environments
      that may speed up the evolution of oviposition behavior, performance related
      traits, morphology and, incidentally, reproductive isolation. In the genus
      Drosophila, cactophilic species of the repleta group include emblematic species
      in the study of the evolution of host plant utilization. The South American D.
      buzzatii and its sibling D. koepferae are a model system for the study of
      differential host plant use. Though these species exhibit a certain degree of
      niche overlap, the former breeds primarily on decaying cladodes of Opuntia cacti
      while the D. koepferae main hosts are columnar cacti of the genus Trichocereus.
      Opuntia sulphurea and T. terscheckii are the among the main hosts in nature.
      These cacti differ in ecological (spatial and temporal predictability) and
      chemical characteristics. Particularly relevant is the presence of toxic
      alkaloids in T. terscheckii. Studies of the effects of these cacti and alkaloids
      revealed the remarkable impact on oviposition behavior, viability, developmental
      time, wing morphology, mating success and developmental stability in both
      species. Recent whole-genome expression studies showed that expression profiles
      are massively affected by the rearing cactus, and that the presence of alkaloids
      is the main factor modulating gene expression in D. buzzatii. Functional
      enrichment analysis indicated that differentially expressed genes are related to
      detoxification processes and stress response; though genes involved in
      development are an important part of the transcriptomic response. The
      implications of our studies in the evolution of host plant use in the repleta
      group are discussed.

PMID- 30107511
TI  - Diagnostic performance of on-site computed CT-fractional flow reserve based on
      fluid structure interactions: comparison with invasive fractional flow reserve
      and instantaneous wave-free ratio.
AB  - Aims: We evaluated diagnostic accuracy of CT-fractional flow reserve (CT-FFR)
      computed on-site with a new vendor workstation, against invasive FFR as the
      reference standard. Methods and results: Retrospective analyses compared CT-FFR
      of 104 vessels with 30-90% diameter stenosis in 75 patients imaged using single
      rotation 320 detector-row coronary CT angiography (CCTA) with invasive FFR
      performed within 90 days. Prospective ECG-gated CCTA included exposure of 70-99%
      of the R-R interval. CT-FFR was computed on-site within the same physical space
      as the CT scanner and reading room. The diagnostic accuracy of CCTA >50% and CT
      FFR <=0.8 to detect hemodynamically significant stenosis, defined as FFR <=0.8,
      was determined, as was the correlation of CT-FFR to FFR and instantaneous wave
      free ratio (iFR). Forty-four vessels (42.3%) had an invasive FFR <=0.8. The
      sensitivity, specificity, positive, and negative predictive value of CT-FFR <=0.8
      vs. CCTA >50% to detect hemodynamically significant stenosis defined as FFR <=0.8
      were 90.9% vs. 70.5%, 78.3% vs. 43.3%, 75.5% vs. 47.7%, and 92.2% vs. 66.7%,
      respectively. Area under the curve of CT-FFR was significantly higher than CCTA
      >50% [0.85, 95% confidence interval (CI): 0.76-0.91 vs. 0.57, 95% CI: 0.47-0.67;
      P < 0.0001]. The correlation coefficient between CT-FFR and iFR was r = 0.62 (95%
      CI: 0.40-0.77, P < 0.0001) and that between CT-FFR and invasive FFR was r = 0.52
      (95% CI: 0.28-0.70, P = 0.0001). CT-FFR inter- and intra-observer correlations
      were excellent (r = 0.83 and r = 0.82, respectively). Conclusion: Locally
      computed CT-FFR based on fluid structure interaction has excellent diagnostic
      accuracy to detect a significant FFR <=0.8 compared with conventional CCTA and
      high reproducibility.

PMID- 30107512
TI  - Forecasting Dose from Unobserved Times: Case Study of Transient Workers at a
      Nuclear Power Plant.
AB  - Objectives: To evaluate the likelihood of exceeding the occupational exposure
      limit (OEL) for annual ionizing radiation doses among transient workers at the
      Hope Creek Nuclear Generating Station, and to propose a method for forecasting
      exposures among transient workers in general. Methods: We obtained personal
      dosimeter data from the Hope Creek Nuclear Generating Station for the period of
      January-December 2014, comprising 1955 monthly dose measurements from 498
      transient workers. The majority of the transient workers (96%) did not report 12
      months of data. The missing months indicate that transient workers may receive
      ionizing radiation doses at other nuclear power plants throughout the year. We
      estimated the likelihood of a worker exceeding the Nuclear Regulatory
      Commission's annual OEL of 5000 mrem. To do so, we had to account both for left
      censored data below the limit of detection (27% of all measurements) and make
      assumptions about doses received during months not employed at the facility. We
      used a maximum likelihood estimation method for non-detected measurements that
      accounted for repeated measurements on an individual. To account for missing
      months of measurements, we considered two extreme scenarios: the best case of
      workers who receive zero exposures outside of the Hope Creek, and the
      illustrative worst case of workers who receive multiple exposures at other
      nuclear power plants with similar exposure scenarios to Hope Creek. We employed a
      bootstrap procedure to forecast annual personal doses under both scenarios, while
      imputing non-detected measurements. Results: None of the workers' reported
      measurements exceeded the OEL. Bootstrapped annual exposure doses revealed
      similar patterns, with a very small likelihood of exceeding the OEL, but great
      potential for variability. Some workers under the best-case scenario may reach
      Hope Creek's 2000 mrem internal action limit if exposed at the 98th percentile of
      their projected annual dose. This scenario becomes more likely when assuming that
      a worker received doses at other nuclear power plants besides Hope Creek
      throughout the year. Conclusions: The Hope Creek Nuclear Generating Station
      appears to be typical of its industry peers in terms of annual ionizing radiation
      doses, which makes it a good test subject for predicting worker doses received
      elsewhere. Transient workers may receive doses at more than one nuclear power
      plant throughout the year, which makes them especially at risk for overexposure.
      The presence of internal plant monitoring systems and the use of tools such as
      bootstrapping to predict compliance are therefore important for health
      protection. An argument can also be made for better tracking of exposures in real
      time of transient workers across facilities. Our method applies to transient
      workers in any industry for whom exposure assessment is complicated by gaps in
      exposure histories and records.

PMID- 30107513
TI  - Fascicular Ratio Pilot Study: High-Resolution Neurosonography-A Possible Tool for
      Quantitative Assessment of Traumatic Peripheral Nerve Lesions Before and After
      Nerve Surgery.
AB  - BACKGROUND: Clinical and electrophysiological assessments prevail in evaluation
      of traumatic nerve lesions and their regeneration following nerve surgery in
      humans. Recently, high-resolution neurosonography (HRNS) and magnetic resonance
      neurography have gained significant importance in peripheral nerve imaging. The
      use of the grey-scale-based "fascicular ratio" (FR) was established using both
      modalities allowing for quantitative assessment. OBJECTIVE: To find out whether
      FR using HRNS can assess nerve trauma and structural reorganization in
      correlation to postoperative clinical development. METHODS: Retrospectively, 16
      patients with operated traumatic peripheral nerve lesions were included. The
      control group consisted of 6 healthy volunteers. All imaging was performed with a
      15 to 6 MHz ultrasound probe (SonoSite X-Porte; Fujifilm, Tokyo, Japan). FR was
      calculated using Fiji () on 8-bit-images ("MaxEntropy" using "Auto-Threshold"
      plug-in). RESULTS: Thirteen of 16 patients required autologous nerve grafting and
      3 of 16 extra-intraneural neurolysis. There was no statistical difference between
      the FR of nonaffected patients' nerve portion with 43.48% and controls with FR
      48.12%. The neuromatous nerve portion in grafted patients differed significantly
      with 85.05%. Postoperatively, FR values returned to normal with a mean of 39.33%.
      In the neurolyzed patients, FR in the affected portion was 78.54%. After
      neurolysis, FR returned to healthy values (50.79%). Ten of 16 patients showed
      clinical reinnervation. CONCLUSION: To our best knowledge, this is the first
      description of FR using HRNS for quantitative assessment of nerve damage and
      postoperative structural reorganization. Our results show a significant
      difference in healthy vs lesioned nerves and a change in recovering nerve
      portions towards a more "physiological" ratio. Further evaluation in larger
      patient groups is required.

PMID- 30107514
TI  - Restrictive compared with liberal red cell transfusion strategies in cardiac
      surgery: a meta-analysis.
AB  - Aims: To determine whether a restrictive strategy of red blood cell (RBC)
      transfusion at lower haemoglobin concentrations is inferior to a liberal strategy
      of RBC transfusion at higher haemoglobin concentrations in patients undergoing
      cardiac surgery. Methods and results: We conducted a systematic review, meta
      analysis, and trial sequential analysis of randomized controlled trials of the
      effect of restrictive and liberal RBC transfusion strategies on mortality within
      30 days of surgery as the primary outcome. Secondary outcomes were those
      potentially resulting from anaemia-induced tissue hypoxia and transfusion
      outcomes. We searched the electronic databases MEDLINE, EMBASE, and the Cochrane
      Library until 17 November 2017. Thirteen trials were included. The risk ratio
      (RR) of mortality derived from 4545 patients assigned to a restrictive strategy
      when compared with 4547 transfused according to a liberal strategy was 0.96 [95%
      confidence interval (CI) 0.76-1.21, I2 = 0]. A restrictive strategy did not have
      a statistically significant effect on the risk of myocardial infarction (RR 1.01,
      95% CI 0.81-1.26; I2=0), stroke (RR 0.93, 95% CI 0.68-1.27, I2 = 0), renal
      failure (RR 0.96, 95% CI 0.76-1.20, I2 = 0), or infection (RR 1.12, 95% CI 0.98
      1.29, I2 = 0). Subgroup analysis of adult and paediatric trials did not show a
      significant interaction. At approximately 70% of the critical information size,
      the meta-analysis of mortality crossed the futility boundary for inferiority of
      the restrictive strategy. Conclusion: The current evidence does not support the
      notion that restrictive RBC transfusion strategies are inferior to liberal RBC
      strategies in patients undergoing cardiac surgery.

PMID- 30107515
TI  - Asleep blood pressure: significant prognostic marker of vascular risk and
      therapeutic target for prevention.
AB  - Aims: Sleep-time blood pressure (BP) is a stronger risk factor for cardiovascular
      disease (CVD) events than awake and 24 h BP means, but the potential role of
      asleep BP as therapeutic target for diminishing CVD risk is uncertain. We
      investigated whether CVD risk reduction is most associated with progressive
      decrease of either office or ambulatory awake or asleep BP mean. Methods and
      results: We prospectively evaluated 18 078 individuals with baseline ambulatory
      BP ranging from normotension to hypertension. At inclusion and at scheduled
      visits (mainly annually) during follow-up, ambulatory BP was measured for 48
      consecutive hours. During the 5.1-year median follow-up, 2311 individuals had
      events, including 1209 experiencing the primary outcome (composite of CVD death,
      myocardial infarction, coronary revascularization, heart failure, and stroke).
      The asleep systolic blood pressure (SBP) mean was the most significant BP-derived
      risk factor for the primary outcome [hazard ratio 1.29 (95% CI) 1.22-1.35 per SD
      elevation, P < 0.001], regardless of office [1.03 (0.97-1.09), P = 0.32], and
      awake SBP [1.02 (0.94-1.10), P = 0.68]. Most important, the progressive
      attenuation of asleep SBP was the most significant marker of event-free survival
      [0.75 (95% CI 0.69-0.82) per SD decrease, P < 0.001], regardless of changes in
      office [1.07 (0.97-1.17), P = 0.18], or awake SBP mean [0.96 (0.85-1.08), P =
      0.47] during follow-up. Conclusion: Asleep SBP is the most significant BP-derived
      risk factor for CVD events. Furthermore, treatment-induced decrease of asleep,
      but not awake SBP, a novel hypertension therapeutic target requiring periodic
      patient evaluation by ambulatory monitoring, is associated with significantly
      lower risk for CVD morbidity and mortality.

PMID- 30107517
TI  - Lower- and Higher-Level Social Cognitive Factors Across Individuals With
      Schizophrenia Spectrum Disorders and Healthy Controls: Relationship With
      Neurocognition and Functional Outcome.
AB  - Background: Schizophrenia spectrum disorders (SSDs) often feature social
      cognitive deficits. However, little work has focused on the factor structure of
      social cognition, and results have been inconsistent in schizophrenia. This study
      aimed to elucidate the factor structure of social cognition across people with
      SSDs and healthy controls. It was hypothesized that a 2-factor model, including
      lower-level "simulation" and higher-level "mentalizing" factors, would
      demonstrate the best fit across participants. Methods: Participants with SSDs (N
      = 164) and healthy controls (N = 102) completed social cognitive tasks ranging
      from emotion recognition to complex mental state inference, as well as clinical
      and functional outcome, and neurocognitive measures. Structural equation modeling
      was used to test social cognitive models, models of social cognition and
      neurocognition, measurement invariance between cases and controls, and
      relationships with outcome measures. Results: A 2-factor (simulation and
      mentalizing) model fit the social cognitive data best across participants and
      showed adequate measurement invariance in both SSD and control groups. Patients
      showed lower simulation and mentalizing scores than controls, but only
      mentalizing was significantly associated with negative symptoms and functional
      outcome. Social cognition also mediated the relationship between neurocognition
      and both negative symptoms and functional outcome. Conclusions: These results
      uniquely indicate that distinct lower- and higher-level aspects of social
      cognition exist across SSDs and healthy controls. Further, mentalizing may be
      particularly linked to negative symptoms and functional outcome. This informs
      future studies of the neural circuitry underlying social cognition and the
      development of targeted treatment options for improving functional outcome.

PMID- 30107516
TI  - Fragile X mental retardation protein modulates the stability of its m6A-marked
      messenger RNA targets.
AB  - N6-methyladenosine (m6A) is the most prevalent internal modification of mammalian
      messenger RNAs (mRNAs) and long non-coding RNAs. The biological functions of this
      reversible RNA modification can be interpreted by cytoplasmic and nuclear 'm6A
      reader' proteins to fine-tune gene expression, such as mRNA degradation and
      translation initiation. Here we profiled transcriptome-wide m6A sites in adult
      mouse cerebral cortex, underscoring that m6A is a widespread epitranscriptomic
      modification in brain. Interestingly, the mRNA targets of fragile X mental
      retardation protein (FMRP), a selective RNA-binding protein, are enriched for m6A
      marks. Loss of functional FMRP leads to Fragile X syndrome (FXS), the most common
      inherited form of intellectual disability. Transcriptome-wide gene expression
      profiling identified 2035 genes differentially expressed in the absence of FMRP
      in cortex, and 92.5% of 174 downregulated FMRP targets are marked by m6A.
      Biochemical analyses indicate that FMRP binds to the m6A sites of its mRNA
      targets and interacts with m6A reader YTHDF2 in an RNA-independent manner. FMRP
      maintains the stability of its mRNA targets while YTHDF2 promotes the degradation
      of these mRNAs. These data together suggest that FMRP regulates the stability of
      its m6A-marked mRNA targets through YTHDF2, which could potentially contribute to
      the molecular pathogenesis of FXS.

PMID- 30107518
TI  - Multiregional Utilization of a Mobile Device App for Triage and Transfer of Burn
      Patients.
AB  - Technology and telehealth have the potential to optimize burn care in areas
      limited by lack of expertise and geographic distance from a Burn Center. This
      study reports a multicenter, multiregional experience using a mobile phone app to
      facilitate triage of patients by allowing referring providers to send encrypted
      photos, thus enhancing the telephone consultation process. A retrospective review
      was conducted on referrals from August 2016 to July 2017 at three regional Burn
      Centers that utilize the same mobile phone app. Centers studied are located in
      the Western, Northeastern, and Southern regions of the United States. Data on
      numbers of admissions, consults, referral facilities, type of wounds,
      disposition, and distance from the Burn Centers were recorded. A total of 2011
      consults were placed using the mobile phone app from 294 different referring
      facilities spanning seven states. Utilization of the mobile phone app ranged from
      20.4% to 84% among centers. All three centers demonstrated a similar range of
      consult distances (0-289 miles). Overall, the top three referral diagnoses were
      scald, contact, and flame burns. Regional differences included a higher
      percentage of frostbite in the Western region (P < 0.001) and a higher percentage
      of scald burns in the Northeastern and Southern regions (P < 0.001). The majority
      of patients at all centers were referred to outpatient clinics for ongoing burn
      care. Utilization of a mobile phone app appears to be a useful tool in the triage
      of patients, but further studies are warranted to assess the impact on accuracy
      of triage, patient outcomes, and reduction of costs.

PMID- 30107520
TI  - Epigenome-wide association study in whole blood on type 2 diabetes among sub
      Saharan African individuals: findings from the RODAM study.
AB  - Background: Type 2 diabetes (T2D) results from a complex interplay between
      genetics and the environment. Several epigenome-wide association studies (EWAS)
      have found DNA methylation loci associated with T2D in European populations.
      However, data from African populations are lacking. We undertook the first EWAS
      for T2D among sub-Saharan Africans, aiming at identifying ubiquitous and novel
      DNA methylation loci associated with T2D. Methods: The Illumina 450k DNA
      methylation array was used on whole blood samples of 713 Ghanaian participants
      (256 with T2D, 457 controls) from the cross-sectional Research on Obesity and
      Diabetes among African Migrants (RODAM) study. Differentially methylated
      positions (DMPs) for T2D and HbA1c were identified through linear regression
      analysis adjusted for age, sex, estimated cell counts, hybridization batch, array
      position and body mass index (BMI). We also did a candidate analysis of
      previously reported EWAS loci for T2D in non-African populations, identified
      through a systematic literature search. Results: Four DMPs [cg19693031 (TXNIP),
      cg04816311 (C7orf50), cg00574958 (CPT1A), cg07988171 (TPM4)] were associated with
      T2D after correction for inflation by possible systematic biases. The most
      strongly associated DMP-cg19693031, TXNIP (P = 2.6E-19) -showed hypomethylation
      in T2D cases compared with controls. Two out of the four DMPs [cg19693031
      (TXNIP), cg04816311 (C7orf50)] remained associated with T2D after adjustment for
      BMI, and one locus [cg07988171 (TPM4)] that has not been reported previously.
      Conclusions: In this first EWAS for T2D in sub-Saharan Africans, we have
      identified four DMPs at epigenome-wide level, one of which is novel. These
      findings provide insight into the epigenetic loci that underlie the burden of T2D
      in sub-Saharan Africans.

PMID- 30107521
TI  - Loneliness and Telomere Length: Immune and Parasympathetic Function in
      Associations With Accelerated Aging.
AB  - Background: Lonely people's heightened risks for chronic health conditions and
      early mortality may emerge in part through cellular aging. Lonelier people have
      more severe sympathetic responses to acute stress, increasing their risk for
      herpesvirus reactivation, a possible path to shorter telomeres. Parasympathetic
      function may modulate this risk. Purpose: The current study aimed to examine the
      associations among loneliness, herpesvirus reactivation, and telomere length,
      with parasympathetic activity as a moderator, in healthy middle-aged and older
      adults. Methods: A sample of 113 healthy men and women of ages 40-85 provided
      blood samples that were assayed for telomere length, as well as the latent
      herpesviruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV). They also
      provided heart rate variability (HRV), a measure of parasympathetic activity, and
      reported on their feelings of loneliness. Results: Lonelier people with lower HRV
      (i.e., lower parasympathetic activity) had greater CMV reactivation and shorter
      telomeres compared with their less lonely counterparts, above and beyond
      demographics, health behaviors, resting heart rate, and social network size.
      However, loneliness was not associated with viral reactivation or telomere length
      among those with higher HRV. In turn, greater CMV and EBV reactivation was
      associated with shorter telomeres. Conclusions: Taken together, these data
      implicate parasympathetic function in novel links between loneliness and
      accelerated cellular aging.

PMID- 30107519
TI  - Perspective: Should Vitamin E Recommendations for Older Adults Be Increased?
AB  - Current vitamin E requirements are uniformly applied across the population for
      those >14 y of age. However, aging is associated with alterations in cellular and
      physiologic functions, which are affected by vitamin E. Therefore, it is
      questionable whether vitamin E requirements can be uniformly applied to all adult
      age categories. With aging, there is dysregulation of the immune system in which
      there are decreased cell-mediated and pathogen defense responses coupled with an
      overactive, prolonged inflammatory state. Both animal and human studies in the
      aged suggest that intake above currently recommended levels of vitamin E may
      improve immune and inflammatory responses and be associated with a reduced risk
      of infectious disease. We review the evidence that was considered in establishing
      the current requirements for vitamin E and highlight data that should be
      considered in determining the vitamin E requirements in older adults,
      particularly focusing on the evidence suggesting a benefit of increased vitamin E
      intake on immune function and inflammatory processes and resistance to infection.
      The main objective of this Perspective is to initiate the discussion of whether
      the current Dietary Reference Intake for vitamin E should be increased for the
      older population. We make this suggestion on the basis of mechanistic studies
      showing biological plausibility, correction of a major cellular dysfunction in
      older adults, and strong evidence from several animal and a few human studies
      indicating a reduction in risk and morbidity from infections.

PMID- 30107522
TI  - Estimating treatment prolongation for persistent infections.
AB  - Treatment of infectious diseases is often long and requires patients to take
      drugs even after they have seemingly recovered. This is because of a phenomenon
      called persistence, which allows small fractions of the bacterial population to
      survive treatment despite being genetically susceptible. The surviving
      subpopulation is often below detection limit and therefore is empirically
      inaccessible but can cause treatment failure when treatment is terminated
      prematurely. Mathematical models could aid in predicting bacterial survival and
      thereby determine sufficient treatment length. However, the mechanisms of
      persistence are hotly debated, necessitating the development of multiple
      mechanistic models. Here we develop a generalized mathematical framework that can
      accommodate various persistence mechanisms from measurable heterogeneities in
      pathogen populations. It allows the estimation of the relative increase in
      treatment length necessary to eradicate persisters compared to the majority
      population. To simplify and generalize, we separate the model into two parts: the
      distribution of the molecular mechanism of persistence in the bacterial
      population (e.g. number of efflux pumps or target molecules, growth rates) and
      the elimination rate of single bacteria as a function of that phenotype. Thereby,
      we obtain an estimate of the required treatment length for each phenotypic
      subpopulation depending on its size and susceptibility.

PMID- 30107523
TI  - A near complete, chromosome-scale assembly of the black raspberry (Rubus
      occidentalis) genome.
AB  - Background: The fragmented nature of most draft plant genomes has hindered
      downstream gene discovery, trait mapping for breeding, and other functional
      genomics applications. There is a pressing need to improve or finish draft plant
      genome assemblies. Findings: Here, we present a chromosome-scale assembly of the
      black raspberry genome using single-molecule real-time Pacific Biosciences
      sequencing and high-throughput chromatin conformation capture (Hi-C) genome
      scaffolding. The updated V3 assembly has a contig N50 of 5.1 Mb, representing an
      ~200-fold improvement over the previous Illumina-based version. Each of the 235
      contigs was anchored and oriented into seven chromosomes, correcting several
      major misassemblies. Black raspberry V3 contains 47 Mb of new sequences including
      large pericentromeric regions and thousands of previously unannotated protein
      coding genes. Among the new genes are hundreds of expanded tandem gene arrays
      that were collapsed in the Illumina-based assembly. Detailed comparative genomics
      with the high-quality V4 woodland strawberry genome (Fragaria vesca) revealed
      near-perfect 1:1 synteny with dramatic divergence in tandem gene array
      composition. Lineage-specific tandem gene arrays in black raspberry are related
      to agronomic traits such as disease resistance and secondary metabolite
      biosynthesis. Conclusions: The improved resolution of tandem gene arrays
      highlights the need to reassemble these highly complex and biologically important
      regions in draft plant genomes. The updated, high-quality black raspberry
      reference genome will be useful for comparative genomics across the
      horticulturally important Rosaceae family and enable the development of marker
      assisted breeding in Rubus.

PMID- 30107524
TI  - Conceptual framework for investigating causal effects from observational data in
      livestock.
AB  - Understanding causal mechanisms among variables is critical to efficient
      management of complex biological systems such as animal agriculture production.
      The increasing availability of data from commercial livestock operations offers
      unique opportunities for attaining causal insight, despite the inherently
      observational nature of these data. Causal claims based on observational data are
      substantiated by recent theoretical and methodological developments in the
      rapidly evolving field of causal inference. Thus, the objectives of this review
      are as follows: 1) to introduce a unifying conceptual framework for investigating
      causal effects from observational data in livestock, 2) to illustrate its
      implementation in the context of the animal sciences, and 3) to discuss
      opportunities and challenges associated with this framework. Foundational to the
      proposed conceptual framework are graphical objects known as directed acyclic
      graphs (DAGs). As mathematical constructs and practical tools, DAGs encode
      putative structural mechanisms underlying causal models together with their
      probabilistic implications. The process of DAG elicitation and causal
      identification is central to any causal claims based on observational data. We
      further discuss necessary causal assumptions and associated limitations to causal
      inference. Last, we provide practical recommendations to facilitate
      implementation of causal inference from observational data in the context of the
      animal sciences.

PMID- 30107525
TI  - Homologous overexpression of NpDps2 and NpDps5 increases the tolerance for
      oxidative stress in the multicellular cyanobacterium Nostoc punctiforme.
AB  - The filamentous cyanobacterium Nostoc punctiforme has several oxidative stress
      managing systems, including Dps proteins. Dps proteins belong to the ferritin
      superfamily and are involved in abiotic stress management in prokaryotes.
      Previously, we found that one of the five Dps proteins in N. punctiforme, NpDps2,
      was critical for H2O2 tolerance. Stress induced by high light intensities is
      aggravated in N. punctiforme strains deficient of either NpDps2, or the
      bacterioferritin-like NpDps5. Here, we have investigated the capacity of NpDps2
      and NpDps5 to enhance stress tolerance by homologous overexpression of these two
      proteins in N. punctiforme. Both overexpression strains were found to tolerate
      twice as high concentrations of added H2O2 as the control strain, indicating that
      overexpression of either NpDps2 or NpDps5 will enhance the capacity for H2O2
      tolerance. Under high light intensities, the overexpression of the two NpDps did
      not enhance the tolerance against general light-induced stress. However,
      overexpression of the heterocyst-specific NpDps5 in all cells of the filament led
      to a higher amount of chlorophyll-binding proteins per cell during diazotrophic
      growth. The OENpDps5 strain also showed an increased tolerance to ammonium
      induced oxidative stress. Our results provide information of how Dps proteins may
      be utilised for engineering of cyanobacteria with enhanced stress tolerance.

PMID- 30107526
TI  - The genome of the golden apple snail Pomacea canaliculata provides insight into
      stress tolerance and invasive adaptation.
AB  - Background: The golden apple snail (Pomacea canaliculata) is a freshwater snail
      listed among the top 100 worst invasive species worldwide and a noted
      agricultural and quarantine pest that causes great economic losses. It is
      characterized by fast growth, strong stress tolerance, a high reproduction rate,
      and adaptation to a broad range of environments. Results: Here, we used long-read
      sequencing to produce a 440-Mb high-quality, chromosome-level assembly of the P.
      canaliculata genome. In total, 50 Mb (11.4%) repeat sequences and 21,533 gene
      models were identified in the genome. The major findings of this study include
      the recent explosion of DNA/hAT-Charlie transposable elements, the expansion of
      the P450 gene family, and the constitution of the cellular homeostasis system,
      which contributes to ecological plasticity in stress adaptation. In addition, the
      high transcriptional levels of perivitelline genes in the ovary and albumen gland
      promote the function of nutrient supply and defense ability in eggs. Furthermore,
      the gut metagenome also contains diverse genes for food digestion and xenobiotic
      degradation. Conclusions: These findings collectively provide novel insights into
      the molecular mechanisms of the ecological plasticity and high invasiveness.

PMID- 30107527
TI  - Structural dynamics of translation elongation factor Tu during aa-tRNA delivery
      to the ribosome.
AB  - The GTPase elongation factor EF-Tu delivers aminoacyl-tRNAs to the mRNA
      programmed ribosome during translation. Cognate codon-anticodon interaction
      stimulates GTP hydrolysis within EF-Tu. It has been proposed that EF-Tu undergoes
      a large conformational change subsequent to GTP hydrolysis, which results in the
      accommodation of aminoacyl-tRNA into the ribosomal A-site. However, this proposal
      has never been tested directly. Here, we apply single-molecule total internal
      reflection fluorescence microscopy to study the conformational dynamics of EF-Tu
      when bound to the ribosome. Our studies show that GTP hydrolysis initiates a
      partial, comparatively small conformational change of EF-Tu on the ribosome, not
      directly along the path from the solution 'GTP' to the 'GDP' structure. The final
      motion is completed either concomitant with or following dissociation of EF-Tu
      from the ribosome. The structural transition of EF-Tu on the ribosome is slower
      when aa-tRNA binds to a cognate versus a near-cognate codon. The resulting longer
      residence time of EF-Tu on the ribosome may be important for promoting
      accommodation of the cognate aminoacyl-tRNA into the A-site.

PMID- 30107529
TI  - Erratum: Growing cell walls show a gradient of elastic strain across their
      layers.

PMID- 30107528
TI  - Increased levels of RECQ5 shift DNA repair from canonical to alternative
      pathways.
AB  - RECQ5 (RECQL5) is one of several human helicases that dissociates RAD51-DNA
      filaments. The gene that encodes RECQ5 is frequently amplified in human tumors,
      but it is not known whether amplification correlates with increased gene
      expression, or how increased RECQ5 levels affect DNA repair at nicks and double
      strand breaks. Here, we address these questions. We show that RECQ5 gene
      amplification correlates with increased gene expression in human tumors, by in
      silico analysis of over 9000 individual tumors representing 32 tumor types in the
      TCGA dataset. We demonstrate that, at double-strand breaks, increased RECQ5
      levels inhibited canonical homology-directed repair (HDR) by double-stranded DNA
      donors, phenocopying the effect of BRCA deficiency. Conversely, at nicks,
      increased RECQ5 levels stimulated 'alternative' HDR by single-stranded DNA
      donors, which is normally suppressed by RAD51; this was accompanied by
      stimulation of mutagenic end-joining. Even modest changes (2-fold) in RECQ5
      levels caused significant dysregulation of repair, especially HDR. These results
      suggest that in some tumors, RECQ5 gene amplification may have profound
      consequences for genomic instability.

PMID- 30107530
TI  - Lattice and continuum modelling of a bioactive porous tissue scaffold.
AB  - A contemporary procedure to grow artificial tissue is to seed cells onto a porous
      biomaterial scaffold and culture it within a perfusion bioreactor to facilitate
      the transport of nutrients to growing cells. Typical models of cell growth for
      tissue engineering applications make use of spatially homogeneous or spatially
      continuous equations to model cell growth, flow of culture medium, nutrient
      transport and their interactions. The network structure of the physical porous
      scaffold is often incorporated through parameters in these models, either
      phenomenologically or through techniques like mathematical homogenization. We
      derive a model on a square grid lattice to demonstrate the importance of
      explicitly modelling the network structure of the porous scaffold and compare
      results from this model with those from a modified continuum model from the
      literature. We capture two-way coupling between cell growth and fluid flow by
      allowing cells to block pores, and by allowing the shear stress of the fluid to
      affect cell growth and death. We explore a range of parameters for both models
      and demonstrate quantitative and qualitative differences between predictions from
      each of these approaches, including spatial pattern formation and local
      oscillations in cell density present only in the lattice model. These differences
      suggest that for some parameter regimes, corresponding to specific cell types and
      scaffold geometries, the lattice model gives qualitatively different model
      predictions than typical continuum models. Our results inform model selection for
      bioactive porous tissue scaffolds, aiding in the development of successful tissue
      engineering experiments and eventually clinically successful technologies.

PMID- 30107532
TI  - Use and Opinions of Prescription Opioids Among Older American Adults:
      Sociodemographic Predictors.
AB  - Objectives: This study identifies sociodemographic predictors of prescription
      opioid use among older adults (age 65+) during the peak decade of U.S. opioid
      prescription, and tests whether pain level and Medicaid coverage mediate the
      association between low wealth and opioid use. Predictors of prescription
      nonsteroidal anti-inflammatory drug (NSAID) use, and of opinions of both drug
      classes, are also examined. Method: Regressions of opioid and NSAID use on
      sociodemographic characteristics, pain level, and insurance type were conducted
      using Health and Retirement Study 2004 core and 2005 Prescription Drug Study data
      (n=3,721). Mediation analyses were conducted, and user opinions of drug
      importance, quality, and side effects were assessed. Results: Low wealth was a
      strong, consistent predictor of opioid use. Both pain level and Medicaid coverage
      significantly, but only partially, mediated this association. Net of wealth,
      there were no significant associations between education and use of, or opinions
      of, either class of drugs. Discussion: Among older American adults, the poorest
      are disproportionately likely to have been exposed to prescription opioid
      analgesics. Wealth, rather than education, drove social class differences in mid
      2000s opioid use. Opioid-related policies should take into account socioeconomic
      contributors to opioid use, and the needs and treatment histories of chronic pain
      patients.

PMID- 30107531
TI  - Long non-coding RNA H19 regulates endothelial cell aging via inhibition of Stat3
      signaling.
AB  - Aims: Long noncoding RNAs (lncRNAs) have been shown to regulate numerous
      processes in the human genome, but the function of these transcripts in vascular
      aging is largely unknown. We aim to characterize the expression of lncRNAs in
      endothelial aging and analyze the function of the highly conserved lncRNA H19.
      Methods and Results: H19 was downregulated in endothelium of aged mice. In human
      atherosclerotic plaques H19 was mainly expressed by endothelial cells and H19 was
      significantly reduced in comparison to healthy carotid artery biopsies. Loss of
      H19 led to an upregulation of p16 and p21, reduced proliferation and increased
      senescence in vitro. Depletion of H19 in aortic rings of young mice inhibited
      sprouting capacity. We generated endothelial specific inducible H19 deficient
      mice (H19iEC-KO), resulting in increased systolic blood pressure compared to
      control littermates (Ctrl). These H19iEC-KO and Ctrl mice were subjected to
      hindlimb ischemia, which showed reduced capillary density in H19iEC-KO mice.
      Mechanistically, exon array analysis revealed an involvement of H19 in IL-6
      signaling. Accordingly, ICAM-1 and VCAM-1 were upregulated upon H19 depletion. A
      luciferase reporter screen for differential transcription factor activity
      revealed STAT3 as being induced upon H19 depletion and repressed after H19
      overexpression. Furthermore, depletion of H19 increased the phosphorylation of
      STAT3 at TYR705 and pharmacological inhibition of STAT3 activation abolished the
      effects of H19 silencing on p21 and VCAM-1 expression as well as proliferation.
      Conclusion: These data reveal a pivotal role for the lncRNA H19 in controlling
      endothelial cell aging.

PMID- 30107534
TI  - Distinct fNIRS-derived HbO2 trajectories during the course and over repeated
      walking trials under single and dual-task conditions: implications for within
      session learning and prefrontal cortex efficiency in older adults.
AB  - Background: Neural trajectories of gait are not well established. We determined
      two distinct, clinically relevant neural trajectories, operationalized via
      functional-Near-Infrared-Spectroscopy (fNIRS) HbO2 measures in the prefrontal
      cortex (PFC), under single-task-walk (STW) and dual-task-walk (DTW) conditions.
      Course trajectory assessed neural activity associated with attention during the
      course of a walking task; the second trajectory assessed neural activity
      associated with learning over repeated walking trials. Improved neural efficiency
      was defined as reduced PFC HbO2 after practice. Methods: Walking was assessed
      under STW and DTW conditions. fNIRS was utilized to quantify HbO2 in the PFC
      while walking. Burst measurement included three repeated trials for each
      experimental condition. The course of each walking task consisted of six
      consecutive segments. Results: 83 non-demented participants (mean age=78.05+/
      6.37ys; %female=49.5) were included. Stride velocity (estimate=-0.5259cm/sec,
      p=<0.0001) and the rate of correct letter generation (log estimate of rate ratio=
      0.0377, p<0.0001) declined during the course of DTW. In contrast, stride velocity
      (estimate=1.4577 cm/sec, p<0.0001) and the rate of correct letter generation (log
      estimate of rate ratio=0.0578, p<0.0001) improved over repeated DTW trials.
      Course and trial effects were not significant in STW. HbO2 increased during the
      course of DTW (estimate=0.0454MUM, p<0.0001) but declined over repeated trials
      (estimate=-0.1786MUM, p<0.0001). HbO2 declined during the course of STW
      (estimate=-0.0542MUM, p<0.0001) but didn't change significantly over repeated
      trials. Conclusion: We provided evidence for distinct attention (course) and
      learning (repeated trials) trajectories and their corresponding PFC activity.
      Findings suggest that learning and improved PFC efficiency were demonstrated in
      one experimental session involving repeated DTW trials.

PMID- 30107535
TI  - Poor maternal anthropometric characteristics and newborns' birth weight and
      length: a cross-sectional study in Benin.
AB  - Background: Maternal undernutrition is known to negatively impact newborns' birth
      weight and length, but this finding is poorly documented in the Beninese
      population. This study aimed to assess the effect of maternal anthropometry on
      mean birth weight and length in a Beninese cohort of newborns. Methods: A cross
      sectional study was carried out in Tori Bossito, Republic of Benin. Pregnant
      women attending maternity wards between June 2007 and July 2008 were recruited.
      At delivery the women's characteristics, including weight and height, were
      gathered and newborns' birth weights and lengths were measured. Statistical
      analysis was performed using multiple linear regression. Results: A total of 526
      mother-infant pairs were enrolled; 29.8% of women had low weight status and 26.2%
      had short stature (<155 cm). The mean birth weight was 2985 g (standard deviation
      [SD] 384) the mean birth length was 48.7 cm (SD 2.2). Maternal low weight status
      (coefficient=-151.81, p<0.001) and short stature (coefficient=-135.49, p<0.001)
      reduced the mean birth weight. Similar results were found for mean birth length,
      which was decreased by maternal low weight status (coefficient=-0.42, p=0.04) and
      short stature (coefficient=-0.51, p=0.01). Conclusion: Maternal undernutrition
      expressed by low anthropometry remains problematic in the Beninese population and
      induces transmission of malnutrition. Nutritional interventions are required to
      break this vicious cycle.

PMID- 30107533
TI  - SYT1-associated neurodevelopmental disorder: a case series.
AB  - Synaptotagmin 1 (SYT1) is a critical mediator of fast, synchronous, calcium
      dependent neurotransmitter release and also modulates synaptic vesicle
      endocytosis. This paper describes 11 patients with de novo heterozygous missense
      mutations in SYT1. All mutations alter highly conserved residues, and cluster in
      two regions of the SYT1 C2B domain at positions Met303 (M303K), Asp304 (D304G),
      Asp366 (D366E), Ile368 (I368T) and Asn371 (N371K). Phenotypic features include
      infantile hypotonia, congenital ophthalmic abnormalities, childhood-onset
      hyperkinetic movement disorders, motor stereotypies, and developmental delay
      varying in severity from moderate to profound. Behavioural characteristics
      include sleep disturbance and episodic agitation. Absence of epileptic seizures
      and normal orbitofrontal head circumference are important negative features.
      Structural MRI is unremarkable but EEG disturbance is universal, characterized by
      intermittent low frequency high amplitude oscillations. The functional impact of
      these five de novo SYT1 mutations has been assessed by expressing rat SYT1
      protein containing the equivalent human variants in wild-type mouse primary
      hippocampal cultures. All mutant forms of SYT1 were expressed at levels
      approximately equal to endogenous wild-type protein, and correctly localized to
      nerve terminals at rest, except for SYT1M303K, which was expressed at a lower
      level and failed to localize at nerve terminals. Following stimulation, SYT1I368T
      and SYT1N371K relocalized to nerve terminals at least as efficiently as wild-type
      SYT1. However, SYT1D304G and SYT1D366E failed to relocalize to nerve terminals
      following stimulation, indicative of impairments in endocytic retrieval and
      trafficking of SYT1. In addition, the presence of SYT1 variants at nerve
      terminals induced a slowing of exocytic rate following sustained action potential
      stimulation. The extent of disturbance to synaptic vesicle kinetics is mirrored
      by the severity of the affected individuals' phenotypes, suggesting that the
      efficiency of SYT1-mediated neurotransmitter release is critical to cognitive
      development. In summary, de novo dominant SYT1 missense mutations are associated
      with a recognizable neurodevelopmental syndrome, and further cases can now be
      diagnosed based on clinical features, electrophysiological signature and mutation
      characteristics. Variation in phenotype severity may reflect mutation-specific
      impact on the diverse physiological functions of SYT1.

PMID- 30107536
TI  - The Soluble Fiber alpha-Cyclodextrin Does Not Increase the Fecal Losses of
      Dietary Fat in Adults-A Double-Blind, Randomized, Placebo-Controlled, Crossover
      Trial.
AB  - Background: alpha-Cyclodextrin (alpha-CD), a soluble dietary fiber, may improve
      abnormal plasma lipids and promote weight loss. Preliminary evidence suggests
      that it may exert these effects by binding dietary fat and reducing absorption;
      this has not been tested in humans. Objective: The primary objective was to test
      whether supplemental alpha-CD increases fecal content of dietary lipid in humans.
      Methods: This was a randomized, double-blind, placebo-controlled, crossover study
      completed at the Mayo Clinic. Eight healthy volunteers, 5 premenopausal women and
      3 men ages 23-54 y with body mass index (BMI; kg/m2) 18-27, underwent 2 separate
      study visits with a >=2-wk washout period. The first morning of each visit
      volunteers consumed a standardized breakfast (14.5% protein, 27.5% fat, 60%
      carbohydrate, and 1.5 kcal/mL) containing [14C]tripalmitin and [3H]triolein with
      2 g of alpha-CD or placebo, followed by 2 g of alpha-CD or placebo per meal for 2
      more days. Volunteers consumed 100 g/d of dietary fat. Feces were collected for
      72 h after the labeled breakfast to measure radiotracer content and total fecal
      fat. Radiotracer appearance in plasma TGs was measured at intervals after the
      labeled meal as a secondary outcome. Results: Virtually no 3H radiotracer, but an
      average of ~20% of the 14C radiotracer was recovered in fecal lipids, with no
      difference between alpha-CD and placebo. Total fecal fat content and radiotracer
      appearance in postprandial plasma TGs did not differ between the alpha-CD and
      placebo treatments. Plasma appearance of 14C-TG was 37% +/- 14% less (P < 0.0001)
      than 3H-TG. Conclusions: alpha-CD supplementation did not increase loss of
      dietary lipid in stool or total fecal fat compared with placebo in healthy
      adults. Greater stool loss and lesser appearance in plasma TGs of tripalmitin
      derived [14C] compared with triolein-derived [3H] TGs imply different metabolic
      handling of these 2 dietary fat tracers. This trial was registered at
      www.clinicaltrials.gov as NCT03002168.

PMID- 30107537
TI  - Assessment of the relationship between ovomucin and albumen quality of shell eggs
      during storage.
AB  - Ovomucin is known to be critical for keeping the high quality and freshness of
      thick albumen, but there is lack of understanding on the dynamics changes of this
      important protein during storage. This study aimed to investigate the
      relationship between ovomucin content and egg freshness during storage. Firstly,
      the viscoelasticity of albumen was shown to be much higher than that of ovomucin
      depleted albumen from rheological analysis results, indicating that ovomucin is
      an important component in maintaining the natural viscoelasticity of albumen.
      Then, the ovomucin content determined by ELISA method was compared to albumen pH,
      Haugh unit (HU), and yolk index in terms of egg white quality and to the time of
      storage in terms of egg freshness at 4 degrees C, 25 degrees C, and 37 degrees C,
      respectively. Results of the transformation kinetic showed a decrease in ovomucin
      content with prolonged storage time (P <= 0.01). Correlation analysis showed a
      high positive correlation between ovomucin content and HU (P <= 0.01) and a high
      negative correlation between ovomucin content and the albumen pH (P <= 0.01) at
      the test temperatures. We therefore conclude that ovomucin content in albumen can
      be used as an index for egg freshness. At last, predictive models of the
      equivalent egg age (4 degrees C and 25 degrees C) for evaluating the egg
      freshness were established by means of exponential regression model with ovomucin
      content as the variable. These results can provide a theoretical and technical
      basis for the storage and fresh evaluation of shell eggs.

PMID- 30107538
TI  - Knock-Down of Arabidopsis PLC5 Reduces Primary Root Growth and Secondary Root
      Formation While Overexpression Improves Drought Tolerance and Causes Stunted Root
      Hair Growth.
AB  - Phospholipase C (PLC) is a well-known signaling enzyme in metazoans that
      hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5
      trisphosphate and diacylglycerol as second messengers involved in mutiple
      processes. Plants contain PLC too, but relatively little is known about its
      function there. The model system Arabidopsis thaliana contains nine PLC genes.
      Reversed genetics have implicated several roles for PLCs in plant development and
      stress signaling. Here, PLC5 is functionally addressed. Promoter-beta
      glucuronidase (GUS) analyses revealed expression in roots, leaves and flowers,
      predominantly in vascular tissue, most probably phloem companion cells, but also
      in guard cells, trichomes and root apical meristem. Only one plc5-1 knock-down
      mutant was obtained, which developed normally but grew more slowly and exhibited
      reduced primary root growth and decreased lateral root numbers. These phenotypes
      could be complemented by expressing the wild-type gene behind its own promoter.
      Overexpression of PLC5 (PLC5-OE) using the UBQ10 promoter resulted in reduced
      primary and secondary root growth, stunted root hairs, decreased stomatal
      aperture and improved drought tolerance. PLC5-OE lines exhibited strongly reduced
      phosphatidylinositol 4-monophosphate (PIP) and PIP2 levels and increased amounts
      of phosphatidic acid, indicating enhanced PLC activity in vivo. Reduced PIP2
      levels and stunted root hair growth of PLC5-OE seedlings could be recovered by
      inducible overexpression of a root hair-specific PIP 5-kinase, PIP5K3. Our
      results show that PLC5 is involved in primary and secondary root growth and that
      its overexpression improves drought tolerance. Independently, we provide new
      evidence that PIP2 is essential for the polar tip growth of root hairs.

PMID- 30107540
TI  - Thromboembolic acute myocardial infarction after aortic valve replacement using
      the Freestyle stentless aortic bioprosthesis with subcoronary valve replacement.
AB  - A 70-year-old woman with substernal chest pain lasting 2.5 h presented to the
      emergency department of our hospital. She had a history of aortic valve
      replacement with the Freestyle stentless aortic bioprosthesis for severe aortic
      regurgitation 7 years ago. The initial electrocardiogram showed sinus rhythm at a
      rate of 71 bpm with ST-segment slight elevation in leads II, III and aVF. She was
      diagnosed as having acute coronary syndrome and was referred for an urgent
      catheterization. Urgent coronary angiography revealed total occlusion in the
      distal segment of the right coronary artery. Furthermore, a cavity was revealed
      around the aortic annulus by the contrast leaked from the ostium of the right
      coronary artery during angiography. Contrast-enhanced computed tomography showed
      an enhanced cavity between the native aortic wall and the bioprosthesis and the
      defect in the cavity. We diagnosed the incompetence of the bioprosthesis and
      decided to perform repeat aortic valve replacement. During surgery, the presence
      of a thrombus was confirmed in the cavity. The finding indicated that this
      embolic event was due to the thrombus from the cavity.

PMID- 30107539
TI  - Deposition of Phosphorylated alpha-Synuclein in the rTg4510 Mouse Model of
      Tauopathy.
AB  - The accumulation of specific phosphorylated protein aggregates in the brain is a
      hallmark of severe neurodegenerative disorders. Specifically, hyperphosphorylated
      tau (hp-tau) accumulates in Alzheimer disease, frontotemporal dementia with
      Parkinsonism linked to chromosome 17, and progressive supranuclear palsy;
      furthermore, phosphorylated alpha-synuclein (p-alphaSyn) accumulates in Parkinson
      disease, dementia with Lewy bodies, and multiple system atrophy. Moreover,
      codeposition of different pathological protein aggregates is common in the brains
      of individuals with neurodegenerative diseases. In the present report, we
      describe the detection of p-alphaSyn aggregates in the brain of rTg4510 mice that
      overexpress human P301L mutant tau. Immunohistochemistry showed that hp-tau and p
      alphaSyn aggregates were found within the same neuronal cells in rTg4510 mice and
      increased with age. Moreover, semiquantitative analysis revealed a significant
      regional correlation between hp-tau and p-alphaSyn accumulation. These results
      indicate that endogenous mouse alphaSyn protein is phosphorylated and accumulates
      with hp-tau aggregation in neurons and suggest that the overexpression of human
      P301L mutant tau may enhance endogenous alphaSyn phosphorylation and aggregation
      via a similar hyperphosphorylation mechanism in vivo. This synergic effect
      between tau and alphaSyn accumulation may exacerbate the pathology of several
      neurodegenerative disorders that show a cooccurrence of hp-tau and p-alphaSyn
      aggregation.

PMID- 30107541
TI  - The Proof Is in the Patient: Hepatitis C Virus Microelimination in the Swiss
      Human Immunodeficiency Virus Cohort Study.

PMID- 30107542
TI  - Breast Cancer Screening Using Tomosynthesis or Mammography: A Meta-analysis of
      Cancer Detection and Recall.
AB  - Background: Tomosynthesis approximates a 3D mammogram of the breast, reducing
      parenchymal overlap that masks cancers or creates false "lesions" on 2D
      mammography, and potentially enabling more accurate detection of breast cancer.
      We compared breast cancer screening detection and recall in asymptomatic women
      for tomosynthesis vs 2D mammography. Methods: A systematic review and random
      effects meta-analysis were undertaken. Electronic databases (2009-July 2017) were
      searched for studies comparing tomosynthesis and 2D mammography in asymptomatic
      women who attended population breast cancer screening and reporting cancer
      detection rate (CDR) and recall rate. All statistical tests were two-sided.
      Results: Seventeen studies (1 009 790 participants) were included from 413
      citations. The pooled incremental CDR for tomosynthesis was 1.6 cancers per 1000
      screens (95% confidence interval [CI] = 1.1 to 2.0, P < .001, I2 = 36.9%).
      Incremental CDR was statistically significantly higher for European/Scandinavian
      studies, all using a "paired" design where women had both tests (2.4 per 1000
      screens, 95% CI = 1.9 to 2.9, P < .001, I2 = 0.0%) compared with US ("unpaired")
      studies (1.1 per 1000 screens, 95% CI = 0.8 to 1.5, P < .001, I2 = 0.0%; P < .001
      between strata). The recall rate for tomosynthesis was statistically
      significantly lower than for 2D mammography (pooled absolute reduction = -2.2%,
      95% CI = -3.0 to -1.4, P < .001, I2 = 98.2%). Stratified analyses showed a
      decrease in US studies (pooled difference in recall rate = -2.9%, 95% CI = -3.5
      to -2.4, P < .001, I2 = 92.9%) but not European/Scandinavian studies (0.5%
      increase in recall, 95% CI = -0.1 to 1.2, P = .12, I2 = 93.5%; P < .001 between
      strata). Results were similar in sensitivity analyses excluding studies with
      overlapping cohorts. Conclusions: Tomosynthesis improves CDR and reduces recall;
      however, effects are dependent on screening setting, with greater improvement in
      CDR in European/Scandinavian studies (biennial screening) and reduction in recall
      in US studies with high baseline recall.

PMID- 30107543
TI  - Capping-RACE: a simple, accurate, and sensitive 5' RACE method for use in
      prokaryotes.
AB  - Rapid amplification of cDNA ends (RACE) is a prevalent technique used to obtain
      the 5' ends of transcripts. Several different 5' RACE methods have been
      developed, and one particularly simple and efficient approach called CapFinder
      relies on the 5' cap-dependent template-switching that occurs in eukaryotes.
      However, most prokaryotic transcripts lack a 5' cap structure. Here, we report a
      procedure to capture primary transcripts based on capping the 5'
      triphosphorylated RNA in prokaryotes. Primary transcripts were first treated with
      vaccinia capping enzyme to add a 5' cap structure. First-strand cDNA was then
      synthesized using Moloney murine leukaemia virus reverse transcriptase. Finally,
      a template-switching oligonucleotide with a tail containing three ribonucleic
      acid guanines was hybridized to the cDNA 3' poly(C) and further used as template
      for reverse transcriptase. It is oligonucleotide sequence independent and is more
      sensitive compared to RLM-RACE. This approach specifically identified the
      transcription start sites of ompA, sodB and shiA in Escherichia coli and of ompA,
      rne and rppH in Brucella melitensis. Furthermore, we also successfully identified
      the transcription start sites of small noncoding genes ryhB and micC in E. coli
      and bsnc135 and bsnc149 in B. melitensis. Our findings suggest that Capping-RACE
      is a simple, accurate, and sensitive 5' RACE method for use in prokaryotes.

PMID- 30107544
TI  - Impact of valve culture in the prognosis of active left-sided infective
      endocarditis.
AB  - Background: The culture of removed cardiac tissues during cardiac surgery of left
      sided infective endocarditis (LSIE) helps guiding antibiotic treatment.
      Nevertheless, the prognostic information of a positive valve culture has never
      been explored. Methods: Among 1078 cases of LSIE consecutively diagnosed in three
      tertiary centres we selected those with positive blood cultures, who underwent
      surgery during the active period of infection and in whom surgical biological
      tissues were cultured (n=429). According to microbiological results we
      constructed 2 groups: 218 episodes had negative valve culture and 118 had
      concordant positive valve culture (CPVC). We compared the main features between
      both groups and performed a multivariable analysis of in-hospital mortality.
      Results: Patients with CPVC presented more nosocomial origin (32% vs 20%,
      p=0.014), more septic shock (21% vs 11%, p=0.007) and higher Risk-E score (29% vs
      21%, p=0.023). They developed more heart failure (55% vs 39%, p=0.006) and renal
      failure (60% vs 44%, p=0.006) after surgery, and their in-hospital mortality was
      higher (35% vs 19%, p=0.001), despite an earlier surgery (3 vs 11 days from
      antibiotic beginning, p<0.001). Staphylococcus (61 vs 42%, p=0.001) and
      Enterococcus spp (20% vs 9%, p=0.002) were more frequent in CPVC group while
      Streptococcus spp were less (14% vs 42%, p<0.001). Independent predictors for in
      hospital mortality were renal failure (OR 2.6, CI95% 1.5-4.4), prosthesis (OR
      1.9, CI95% 1.1-3.5), Staphylococcus aureus (OR 1.8, CI95% 1.02-3.3) and
      concordant positive valve culture (OR 2.3, CI95% 1.4-3.9). Conclusion: Valve
      culture in patients with active left-sided IE is an independent predictor of in
      hospital mortality.

PMID- 30107546
TI  - Microbial translocation does not drive immune activation in Ugandan children with
      HIV.
AB  - Objective: Immune activation is associated with morbidity/mortality in HIV
      infection despite antiretroviral therapy (ART). We investigated whether microbial
      translocation drives immune activation in HIV-infected Ugandan children. Methods:
      Nineteen markers of immune activation/inflammation were measured over 96 weeks in
      HIV-infected Ugandan children in CHAPAS-3 (ISRCTN69078957) and HIV-uninfected age
      matched controls. Microbial translocation was assessed using molecular techniques
      including next-generation sequencing. Results: Of 249 children included, 120 were
      HIV-infected ART-naive and 22 ART-experienced (median (IQR) age 2.8(1.7-4.0) and
      6.5(5.9-9.2) years; median baseline CD4% 20(14-24) and 35(31-39)). 107 were HIV
      uninfected controls. Median (IQR) CD4% increase was 17(12-22) at week-96 in ART
      naive children, and viral load was<100 copies/mL in 76%/91% ART
      naive/experienced. Immune activation decreased with ART. Children could be
      divided by immune activation markers into clusters: cluster-1 (majority HIV
      uninfected); cluster-2 (mixed HIV-uninfected/ART-naive/ART-experienced); and
      cluster-3 (majority ART-naive). Immune activation was low in cluster-1, decreased
      in cluster-3, and persisted in cluster-2. Blood microbial DNA levels were
      negative/very low across groups, with no difference between clusters except
      Enterobacteriaceae (higher in cluster-1,p<0.0001). Conclusion: Immune activation
      decreased with ART, with marker-clustering indicating different activation
      patterns by HIV/ART status. Levels of bacterial DNA in blood were low regardless
      of HIV/ART/immune activation status. Microbial translocation did not drive immune
      activation in this setting.

PMID- 30107547
TI  - Maternal nutrient restriction alters uterine artery hemodynamics and placentome
      vascular density in Bos indicus and Bos taurus.
AB  - The objective was to examine uterine artery blood flow (UBF) as well as
      macroscopic and microscopic placentome vascular density in nutrient-restricted
      Angus and Brahman heifers. Angus (n = 6) and Brahman (n = 6) heifers were bred to
      a single sire and pregnancy confirmed at 30-d postbreeding. Heifers were randomly
      assigned to 1 of 2 dietary treatments consisting of 100% (control-fed; CON; n =
      6) or 60% (total nutrient-restricted; RES; n = 6) based from net energy
      requirements for gestating heifers. Nutritional treatments were imposed from days
      50 to 180 of gestation. On day 175 of gestation, UBF was collected ipsilateral
      and contralateral to the conceptus via Doppler ultrasonography. Heifers underwent
      Cesarean sections for collection of 2 adjacent placentomes on day 180 of
      gestation. The primary cotyledonary artery of 1 placentome was perfused with
      Alexa Fluor 647 Con A conjugate to examine macroscopic cotyledonary vascular
      density via an in vivo imaging system. The second placentome was fixed for
      microscopic immunofluorescence labeling of capillaries and separated into
      maternal (caruncle) and fetal (cotyledon) components for determination of
      angiogenic factor mRNA expression. Main effects of nutritional treatment and
      breed are reported in the absence of a significant nutritional treatment by breed
      interaction. Ipsilateral UBF was decreased (P < 0.05) by 48% in RES vs. CON,
      whereas breed did not influence ipsilateral UBF. Contralateral UBF was not
      different between nutritional treatments; however, contralateral UBF was
      decreased (P < 0.05) by 63% in Brahman vs. Angus cattle. Macroscopic cotyledonary
      vascular density was increased (P < 0.05) by 36% in RES vs. CON and 82% in
      Brahman vs. Angus heifers. Percent capillary area and capillary perimeter were
      increased (P < 0.05) in RES vs. CON and increased (P < 0.05) in Brahman vs. Angus
      heifers. Dietary treatments did not alter angiogenic factor expression; however,
      transcript abundance of caruncle and cotyledon ANGP1, FLT1, and KDR was increased
      (P < 0.05) in Brahman vs. Angus heifers. In summary, these data indicate
      compensatory responses in macroscopic and microscopic placentome blood vessel
      density during maternal nutrient restriction-induced reductions in UBF. Moreover,
      a greater macroscopic density of cotyledonary blood vessels was observed in
      Brahman vs. Angus heifers.

PMID- 30107548
TI  - High proportion of drug hypersensitivity reactions to sulfasalazine following its
      use in anti-PD-1-associated inflammatory arthritis.

PMID- 30107545
TI  - Winter-dormant shoot apical meristem in poplar trees shows environmental
      epigenetic memory.
AB  - Trees have a long lifespan and must continually adapt to environmental pressures,
      notably in the context of climate change. Epigenetic mechanisms are doubtless
      involved in phenotypic plasticity and in stress memory; however, little evidence
      of the role of epigenetic processes is available for trees growing in fields.
      Here, we analyzed the possible involvement of epigenetic mechanisms in the winter
      dormant shoot apical meristem of Populus * euramericana clones in memory of the
      growing conditions faced during the vegetative period. We aimed to estimate the
      range of genetic and environmentally induced variations in global DNA methylation
      and to evaluate their correlation with changes in biomass production, identify
      differentially methylated regions (DMRs), and characterize common DMRs between
      experiments. We showed that the variations in global DNA methylation between
      conditions were genotype dependent and correlated with biomass production
      capacity. Microarray chip analysis allowed detection of DMRs 6 months after the
      stressful summer period. The 161 DMRs identified as common to three independent
      experiments most notably targeted abiotic stress and developmental response
      genes. Results are consistent with a winter-dormant shoot apical meristem
      epigenetic memory of stressful environmental conditions that occurred during the
      preceding summer period. This memory may facilitate tree acclimation.

PMID- 30107549
TI  - Vicinal land use change strongly drives stream bacterial community in a tropical
      montane catchment.
AB  - Impact of land use (LU) change on stream environmental conditions and the
      inhabiting bacterial community remains rarely investigated, especially in
      tropical montane catchments. We examined the effects of LU change and its legacy
      along a tropical stream by comparing seasonal patterns of dissolved organic
      carbon (DOC) / colored dissolved organic matter (CDOM) in relation to variations
      in structure, diversity and metabolic capacities of particle-attached (PA) and
      free-living (FL) bacterial communities. We hypothesized that despite seasonal
      differences, hydrological flows that accumulate allochthonous carbon along the
      catchment are a major controlling factor of the bacterial community.
      Surprisingly, local environmental conditions that were largely related to nearby
      LU and the legacy of LU change were more important for stream bacterial diversity
      than hydrological connectivity. DOC was strongly correlated with PA richness and
      diversity. The legacy of LU change between teak plantation and annual crops
      induced high DOC and high diversity and richness of PA in the adjacent waters,
      while banana plantations were associated with high diversity of FL. The community
      structures of both PA and FL differed significantly between seasons. Our results
      highlight the importance of vicinal LU change and its legacy on aquatic bacterial
      communities in mixed used tropical watersheds.

PMID- 30107550
TI  - "I Did Not Tell it to Anyone": Please Pay Attention to the Children of Patients
      Suffering From Psychosis.

PMID- 30107551
TI  - High Cervical Ependymoma Resection: 2-Dimensional Operative Video.
AB  - This operative video illustrates resection of a cervical ependymoma in a 40-yr
      old female with numbness of upper and lower extremities and ataxia. Magnetic
      resonance imaging (MRI) demonstrated an enhancing intramedullary intradural
      spinal mass at C2-3. The patient underwent a posterior cervical laminoplasty for
      tumor resection. This video highlights the natural history of this disease,
      treatment options, surgical procedure, potential risks and complications, and
      postoperative management of ependymomas. A posterior midline skin incision was
      made from the inion to the level of C4 which exposed the posterolateral elements
      of C1-3. C2 and C3 lamina were removed as a single piece using the high-speed
      drill. A C1 laminectomy was then also performed to provide adequate superior
      exposure. The dura was opened widely in the midline. Careful midline myelotomy
      was then performed overlying the tumor. The tumor is noted to be densely adherent
      to the surrounding spinal cord. Gross total resection was completed using
      ultrasonic aspiration and microdissection. The dura was closed in a watertight
      fashion followed by a synthetic dural sealant. The bony elements of C2, C3 were
      then reconstructed using osteoplastic laminoplasty, titanium miniplates, and
      screws at C2-3. The wound was closed in multiple layers using sutures. Specimens
      were sent for frozen and permanent pathological analysis, eventually
      demonstrating WHO grade II ependymoma. There were no complications. Postoperative
      MRI demonstrated gross total resection. The patient had an uneventful
      postoperative course. The strength was at baseline at long term follow-up, with
      small sensory deficit.

PMID- 30107552
TI  - Infliximab Has a Number of Well-Described Adverse Effects. Is Myeloid Metaplasia
      One of These in Elderly Long-standing IBD Patients?

PMID- 30107553
TI  - Titanium dioxide food additive (E171) induces ROS formation and genotoxicity:
      contribution of micro and nano-sized fractions.

PMID- 30107555
TI  - Corrigendum: Sources affecting knowledge and behavior responses to the Zika virus
      in US households with current pregnancy, intended pregnancy and a high
      probability of unintended pregnancy.

PMID- 30107554
TI  - Generating genomic platforms to study Candida albicans pathogenesis.

PMID- 30107556
TI  - Contribution of chronic conditions to disability in men and women in France.
AB  - Background: Women report more disability than men perhaps due to gender
      differences in the prevalence of diseases and/or in their disabling impact. We
      compare the contribution of chronic diseases to disability in men and women in
      France, using a disability survey conducted in both private households and
      institutions, and we also examine the effect of excluding the institutionalized
      population. Methods: Data comprised 17 549 individuals age 50+, who participated
      in the 2008-09 French Disability Health Survey including people living in
      institutions. Disability was defined by limitations in activities people usually
      do due to health problems (global activity limitation indicator). Additive
      regression models were fitted separately by gender to estimate the contribution
      of conditions to disability taking into account multi-morbidity. Results:
      Musculoskeletal diseases caused most disability for both men (10.1%, CI: 8.1
      12.0) and women (16.0%, CI 13.6-18.2). The second contributor for men was heart
      diseases (5.7%, CI: 4.5-6.9%), and for women anxiety-depression (4.0, CI 3.1
      5.0%) closely followed by heart diseases (3.8%, CI 2.9-4.7%). Women's higher
      contribution of musculoskeletal diseases reflected their higher prevalence and
      disabling impact; women's higher contribution of anxiety-depression and lower
      contributions of heart diseases reflected gender differences in prevalence.
      Excluding the institutionalized population did not change the overall
      conclusions. Conclusions: The largest contributors to the higher disability of
      women than men are moderately disabling conditions with a high prevalence.
      Whereas traditional disabling conditions such as musculoskeletal diseases are
      more prevalent and disabling in women, fatal diseases such as cardiovascular
      disease are also important contributors in women and men.

PMID- 30107558
TI  - Comment on: Managing morbidity and treatment-related toxicity in patients with
      ankylosing spondylitis.

PMID- 30107557
TI  - Quantitative vs. qualitative evaluation of static stress computed tomography
      perfusion to detect haemodynamically significant coronary artery disease.
AB  - Aims: To compare the diagnostic accuracy of stress computed tomography myocardial
      perfusion (CTP) for the detection of significant coronary artery disease with
      visual approach vs. quantitative analysis with transmural perfusion ratio (TPR)
      in consecutive symptomatic patients scheduled for invasive coronary angiography
      (ICA) plus invasive fractional flow reserve (FFR). Methods and results: Eighty
      eight consecutive symptomatic patients underwent rest coronary computed
      tomography angiography (cCTA) followed by static stress-CTP. Diagnostic accuracy
      of cCTA + stress-CTP with visual evaluation and with TPR measurement was
      calculated and compared with ICA and invasive FFR. Addition of stress-CTP with
      qualitative evaluation to rest-cCTA showed sensitivity, specificity, negative and
      positive predictive values, and accuracy at a vessel and patient level of 92%,
      92%, 97%, 82%, 92% and 98%, 80%, 97%, 82%, 89%, respectively indicating a
      significant improvement of specificity, positive predictive value, and accuracy
      values vs. rest-cCTA in both models. Similarly, addition of stress-CTP with TPR
      evaluation to rest-cCTA showed sensitivity, specificity, negative and positive
      predictive values, and accuracy at a vessel and patient level of 84%, 90%, 93%,
      76%, 88% and 91%, 71%, 89%, 75%, 81%, respectively indicating a significant
      improvement of specificity, positive predictive value values vs. rest-cCTA only
      in a vessel-based model and of positive predictive value in a patient-based
      model. When cCTA + stress-CTP with qualitative evaluation was compared with cCTA
      + stress-CTP with TPR estimation, no differences were found in terms of
      diagnostic performance. Conclusion: The addition of stress-CTP with visual
      evaluation to cCTA imaging has similar diagnostic performance when compared with
      the quantitative analysis of myocardial perfusion based on TPR measurement.

PMID- 30107559
TI  - The Difference in Surgical Site Infection Rates Between Open and Minimally
      Invasive Spine Surgery for Degenerative Lumbar Pathology: A Retrospective Single
      Center Experience of 1442 Cases.
AB  - BACKGROUND: Surgical site infection (SSI) in spinal surgery contributes to
      significant morbidity and healthcare resource utilization. Few studies have
      directly compared the rate of minimally invasive surgery (MIS) SSI with open
      surgery. OBJECTIVE: To investigate whether MIS techniques had a lower SSI rate in
      degenerative lumbar procedures as compared with traditional open techniques.
      METHODS: A single-center, retrospective review of a prospectively collected
      database was queried from January 2013 to 2016 for adult patients who underwent
      lumbar decompression and/or instrumented fusion for which the surgical indication
      involved degenerative disease. The SSI rate was determined for all procedures as
      well as in the open and minimally invasive groups. Risk factors associated with
      SSI were also reviewed for each patient. RESULTS: A total of 1442 lumbar spinal
      procedures were performed during this time period. Of these, there were 961 MIS
      and 481 open (67% vs 33%, respectively). The overall SSI rate was 1.5% (21/1442).
      The surgical site infection rate for MIS was less than open techniques (0.5% vs
      3.3%; P = .0003). For decompression only, the infection rate for MIS and open was
      0.4% vs 3.9% (P = .04), and for decompression with fusion it was 0.7% vs 2.6%,
      respectively (P = .68). CONCLUSION: Our study demonstrates a significant 7-fold
      reduction in SSIs when comparing MIS with open surgery. This significance was
      also demonstrated with a 10-fold reduction for procedures involving decompression
      alone. Procedures that require fusion as well as decompression showed a trend
      towards a decreased infection rate that did not reach clinical significance.

PMID- 30107560
TI  - The impact of selective genotyping on the response to selection using single-step
      genomic best linear unbiased prediction.
AB  - Across the majority livestock species, routinely collected genomic and pedigree
      information has been incorporated into evaluations using single-step methods. As
      a result, strategies that reduce genotyping costs without reducing the response
      to selection are important as they could have substantial economic impacts on
      breeding programs. Therefore, the objective of the current study was to
      investigate the impact of selectively genotyping selection candidates on the
      selection response using simulation. Populations were simulated to mimic the
      genome and population structure of a swine and cattle population undergoing
      selection on an index comprised of the estimated breeding values (EBV) for 2
      genetically correlated quantitative traits. Ten generations were generated and
      genotyping began generation 7. Two phenotyping scenarios were simulated that
      assumed the first trait was recorded early in life on all individuals and the
      second trait was recorded on all versus a random subset of the individuals. The
      EBV were generated from a bivariate animal model. Multiple genotyping scenarios
      were generated that ranged from not genotyping any selection candidates, a
      proportion of the selection candidates based on either their index value or
      chosen at random, and genotyping all selection candidates. An interim index value
      was utilized to decide who to genotype for the selective genotype strategy. The
      interim value assumed only the first trait was observed and the only genotypic
      information available was on animals in previous generations. Within each
      genotyping scenario 25 replicates were generated. Within each genotyping scenario
      the mean response per generation and the degree to which EBV were
      inflated/deflated was calculated. Across both species and phenotyping strategies,
      the plateau of diminishing returns was observed when 60% of the selection
      candidates with the largest index values were genotyped. When randomly genotyping
      selection candidates, either 80 or 100% of the selection candidates needed to be
      genotyped for there not to be a reduction in the index response. Across both
      populations, no differences in the degree that EBV were inflated/deflated for
      either trait 1 or 2 were observed between nongenotyped and genotyped animals. The
      current study has shown that animals can be selectively genotyped in order to
      optimize the response to selection as a function of the cost to conduct a
      breeding program using single-step genomic best linear unbiased prediction.

PMID- 30107561
TI  - Delayed spironolactone administration prevents the transition from acute kidney
      injury to chronic kidney disease through improving renal inflammation.
AB  - Background: Acute kidney injury (AKI) is not as harmless as previously thought
      since it may lead to chronic kidney disease (CKD). Because most of the time
      ischemic AKI occurs unexpectedly, it is difficult to prevent its occurrence and
      there are no specific therapeutic approaches to prevent the AKI to CKD
      transition. We aimed to determine whether mineralocorticoid receptor blockade
      (MRB) in the first days after ischemia/reperfusion (IR) can prevent progression
      to CKD. Methods: Four groups of male Wistar rats were included: sham and three
      groups of bilateral renal ischemia for 45 min, one without treatment and the
      other two receiving spironolactone for 5 or 10 days, starting 24 h after IR. The
      rats were studied at 10 days or 5 months after ischemia induction. Results: After
      5 months of follow-up, the untreated group exhibited clear evidence of AKI to CKD
      progression, such as proteinuria, reduced renal blood flow, tubulointerstitial
      fibrosis, glomerulosclerosis and glomerular hypertrophy. All these alterations
      were prevented by both spironolactone treatments initiated 24 h after IR, the 10
      day treatment being more effective. Within the early mechanisms of the MRB
      protective effect are the reduction of inflammation and increased endothelin-B
      receptor expression and endothelial nitric oxide synthase activation in the first
      10 days after IR. Conclusions: We propose that MRB, administered 24 h after the
      ischemic injury that leads to AKI, reduces inflammation and promotes efficient
      tissue repair that avoids the AKI to CKD transition. These data highlight a
      therapeutic window to preclude CKD development after AKI.

PMID- 30107563
TI  - Lpp, the Braun lipoprotein, turns 50-major achievements and remaining issues.
AB  - The discovery of Escherichia coli Lpp as the first protein with three acyl groups
      covalently attached to its N-terminal cysteine residue defined a new class of
      bacterial proteins, the lipoproteins. Lipoproteins are extracytoplasmic, globular
      proteins that are anchored to a membrane by a lipid moiety. Being anchored to the
      outer membrane, Lpp, which is also known as the Braun lipoprotein, is small (5.8
      kDa) and folds into a trimeric helical structure. It is also the numerically most
      abundant protein in E. coli. A unique feature of Lpp is that its C-terminal
      lysine residue is covalently attached to the peptidoglycan, providing the only
      covalent connection between the outer membrane and the cell wall. Here, we review
      the knowledge gained on Lpp since its discovery in 1969 until the recent finding
      that Lpp functions as a major size determinant in the bacterial cell envelope. We
      also discuss the role played by Lpp in virulence and highlight the major
      questions that remain to be solved.

PMID- 30107562
TI  - Breed-specific differences in the immune response to lipopolysaccharide in ewes.
AB  - Innate immune response to a lipopolysaccharide (LPS) challenge varies among sheep
      breeds. How different breeds respond to bacterial infections impacts management
      practices of sheep producers. Hence, clinical response, acute-phase response, and
      gene expression of pro- and anti-inflammatory markers in peripheral white blood
      cells (WBCs) were examined after an LPS challenge in Dorset and Suffolk ewes.
      Ewes received either PBS or 2.5 ug/kg LPS (i.v.) 4 to 5 d after onset of
      synchronized estrus. Blood was collected via jugular venipuncture intermittently
      for 24 h to determine WBC counts. Rectal temperatures and observations of
      behavioral/physical appearances were recorded hourly. After LPS, WBCs decreased
      the first hour (P = 0.0001) and rectal temperatures (P < 0.0001) increased
      through 4 h; both returned toward normal 6 h after challenge. Suffolk ewes
      exhibited greater changes in temperature (P = 0.03) and behavioral/physical
      responses (P < 0.0001) than Dorset ewes and had an enhanced acute-phase response
      demonstrated by increased concentrations of plasma haptoglobin (P = 0.04), as
      well as cortisol concentrations (P = 0.03). Real-time PCR was completed on buffy
      coat homogenates for expression of pro-inflammatory [CXCL8, IL-6, interferon
      gamma (IFNG), complement component 3 (C3), toll-like receptor 4 (TLR4),
      prostaglandin synthase 2 (PTGS2)] and anti-inflammatory [IL-10, superoxide
      dismutase 2 (SOD2), forkhead box P3 (FOXP3), peroxisome proliferator-activated
      receptor gamma (PPARG), mannose receptor C type 1 (MRC1), transforming growth
      factor beta (TGFbeta)] genes. After LPS treatment, gene expressions increased for
      CXCL8 (P = 0.0003), TLR4 (P = 0.004), SOD2 (P < 0.0001), and C3 (P = 0.003),
      while PPARG (P = 0.006) and MRC1 (P = 0.003) decreased. Overall, Dorset ewes had
      greater expression of TLR4 (P = 0.003), IL-10 (P = 0.045), PPARG (P = 0.002),
      FOXP3 (P = 0.001), and SOD2 (P = 0.0002), whereas Suffolk ewes had greater
      expression of IL-6 (P = 0.0007), IFNG (P = 0.02), PTGS2 (P = 0.0002), and C3 (P =
      0.008). Suffolk ewes also displayed greater expression of IL-6 (P = 0.002) and C3
      (P = 0.0004) in response to LPS. In conclusion, differences in gene expression
      may explain the enhanced inflammatory response in Suffolk ewes and may predispose
      Suffolk ewes to be more responsive to bacterial infection than Dorset ewes.

PMID- 30107564
TI  - Does health literacy mediate the relationship between socioeconomic status and
      health disparities? Integrative review.
AB  - While socioeconomic disparities are among the most fundamental causes of health
      disparities, socioeconomic status (SES) does not impact health directly. One of
      the potential mediating factors that link SES and health is health literacy (HL).
      Yet although HL can be considered a modifiable risk factor of socioeconomic
      disparities in health, the relationship between SES, HL and health disparities is
      not well understood. This study reviewed the evidence regarding the mediating
      role of HL in the relationship between socioeconomic and health disparities.
      Medline, Cinahl, Embase, PsychInfo, Eric, Web of Science, Google, Google Scholar,
      Mednar, Doaj and Worldcat were used to retrieve studies that specifically
      addressed socioeconomic and socio-demographic factors related to low HL levels,
      as well as the mediating role of HL in the relationship between SES and
      disparities in health outcomes. Selected studies were assessed for methodological
      quality. Sixteen published studies were retained for inclusion and content
      analyzed using the constant comparison method. The review indicates that
      disadvantaged social and socioeconomic conditions contribute to low HL levels,
      whereby low SES, and particularly educational attainment, is the most important
      determinant of HL, and that HL mediates the relationship between SES and health
      status, quality of life, specific health-related outcomes, health behaviors and
      use of preventive services. HL can be considered as a modifiable risk factor of
      socioeconomic disparities in health. Enhancing the level of HL in the population
      or making health services more accessible to people with low HL may be a means to
      reach a greater equity in health.

PMID- 30107567
TI  - Noncontact Measurement of the Deformation of Sternal Skin During Shoulder
      Movements and Upper Extremity Activities Restricted by Sternal Precautions.
AB  - Background: Existing variation has been identified in the rehabilitation programs
      for patients following cardiac surgery. Sternal precautions are believed to be
      overly restrictive and detrimental to patient recovery both physically and
      psychologically. Objective: The objective of this study was to determine the
      deformation of sternal skin during shoulder movements and upper extremity
      activities using a noncontact approach. Design: This was a cross-sectional,
      nonexperimental observational study. Methods: Two black dots were marked on
      participants' skin overlying sternoclavicular joints using an erasable marker.
      The coordinates of the dots were recorded using a digital camera and obtained
      using ImageJ, a public domain image processing program. Skin deformation between
      the 2 dots was quantified as biomechanical strain. Results: The sternal skin
      strain was - 15.3% (SD = 5.6) and - 12.0% (SD = 7.0) at 90 and 180 degrees of
      flexion; 0.0% (SD=0.0) and-12.8% (SD=5.8) at 90 and 180 degrees of abduction; and
      - 6.4% (SD=2.8), - 8.9% (SD=3.8), and - 9.8% (SD=4.6) when lifting the 0-, 5-,
      and 10-lb weights, respectively. The sternal skin strain was 7.9% (SD=3.9) for
      extension to the end range and-2.5% (SD=5.8) for pushing up from a chair. There
      is a trend of strain magnitude decrease with the increase of rhomboid strength,
      but no statistically significant association was found between them (R=0.12).
      Limitations: Limitations included convenience sampling, small sample size, and
      using skin deformation as a proxy for mechanical loading of the bony structures.
      Conclusions: The data do not support the restriction on most of the shoulder
      movements and upper extremity activities following cardiac surgery. The approach
      has the advantage of measuring skin deformation in the entire sternal region.

PMID- 30107565
TI  - E. coli elongation factor Tu bound to a GTP analogue displays an open
      conformation equivalent to the GDP-bound form.
AB  - According to the traditional view, GTPases act as molecular switches, which cycle
      between distinct 'on' and 'off' conformations bound to GTP and GDP, respectively.
      Translation elongation factor EF-Tu is a GTPase essential for prokaryotic protein
      synthesis. In its GTP-bound form, EF-Tu delivers aminoacylated tRNAs to the
      ribosome as a ternary complex. GTP hydrolysis is thought to cause the release of
      EF-Tu from aminoacyl-tRNA and the ribosome due to a dramatic conformational
      change following Pi release. Here, the crystal structure of Escherichia coli EF
      Tu in complex with a non-hydrolysable GTP analogue (GDPNP) has been determined.
      Remarkably, the overall conformation of EF-Tu.GDPNP displays the classical, open
      GDP-bound conformation. This is in accordance with an emerging view that the
      identity of the bound guanine nucleotide is not 'locking' the GTPase in a fixed
      conformation. Using a single-molecule approach, the conformational dynamics of
      various ligand-bound forms of EF-Tu were probed in solution by fluorescence
      resonance energy transfer. The results suggest that EF-Tu, free in solution, may
      sample a wider set of conformations than the structurally well-defined GTP- and
      GDP-forms known from previous X-ray crystallographic studies. Only upon binding,
      as a ternary complex, to the mRNA-programmed ribosome, is the well-known, closed
      GTP-bound conformation, observed.

PMID- 30107568
TI  - A Multi-Center Case-Control Study of the Effect of Acute Rejection and
      Cytomegalovirus Infection on Pneumocystis Pneumonia (PCP) in Solid Organ
      Transplant Recipients.
AB  - Background: Pneumocystis pneumonia (PCP) is associated with morbidity and
      mortality in solid organ transplant (SOT) recipients. In this case-control study,
      we determined the association between post-transplant PCP and 3 variables:
      cytomegalovirus infection, allograft rejection and prophylaxis. Methods: Eight
      transplantation centers participated. For each case (SOT recipient with PCP), 3-5
      controls (SOT recipients without PCP) were included. Controls were matched to the
      cases based on transplant center, type of allograft and date of transplantation
      (+/- 6 months). Results: We enrolled 53 cases and 209 controls. Transplant types
      included kidney (n=198), heart (n=30), liver (n=15), kidney-pancreas (n=14) and
      lung (n=5). PCP occurred beyond 12 months after transplantation in 43 (81.1%)
      cases. Thirty-four cases (64.1%) required admission to ICU and 28 (52.8%) had
      mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases and 14
      (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion
      of female sex (p= 0.009), kidney dysfunction (p=0.001), cardiac diseases
      (p=0.005), diabetes mellitus (p=0.03), allograft rejection (p=0.001), CMV
      infection (p=0.001) and severe lymphopenia (p=0.001) were significantly higher in
      cases. In logistic regression model, CMV infection (adjusted OR: 4.6, 95% CI: 2.0
      10.5) and allograft rejection (adjusted OR: 3.0, 95% CI: 1.5- 6.1) significantly
      increased the likelihood of PCP. Conclusions: PCP was mostly a late-onset disease
      occurring after complete course of prophylaxis particularly among patients with
      CMV infection or allograft rejection. PCP is associated with significant
      allograft loss. Extended prophylaxis targeting recipients with allograft
      rejection or CMV infection may reduce the risk of PCP.

PMID- 30107566
TI  - Revealing a human p53 universe.
AB  - p53 transcriptional networks are well-characterized in many organisms. However, a
      global understanding of requirements for in vivo p53 interactions with DNA and
      relationships with transcription across human biological systems in response to
      various p53 activating situations remains limited. Using a common analysis
      pipeline, we analyzed 41 data sets from genome-wide ChIP-seq studies of which 16
      have associated gene expression data, including our recent primary data with
      normal human lymphocytes. The resulting extensive analysis, accessible at p53
      BAER hub via the UCSC browser, provides a robust platform to characterize p53
      binding throughout the human genome including direct influence on gene expression
      and underlying mechanisms. We establish the impact of spacers and mismatches from
      consensus on p53 binding in vivo and propose that once bound, neither
      significantly influences the likelihood of expression. Our rigorous approach
      revealed a large p53 genome-wide cistrome composed of >900 genes directly
      targeted by p53. Importantly, we identify a core cistrome signature composed of
      genes appearing in over half the data sets, and we identify signatures that are
      treatment- or cell-specific, demonstrating new functions for p53 in cell biology.
      Our analysis reveals a broad homeostatic role for human p53 that is relevant to
      both basic and translational studies.

PMID- 30107570
TI  - CpxR overexpression increases the susceptibility of acrB and cpxR double-deleted
      Salmonella enterica serovar Typhimurium to colistin.
AB  - Background: Colistin has been used as the last therapeutic resort for treatment
      of MDR Gram-negative bacteria infections in humans. The two-component system
      CpxAR has been reported to contribute to the MDR of bacteria. There may be a more
      complex network mediated by CpxAR contributing to colistin susceptibility than
      previously understood. Methods: A series of AcrB or CpxR deletion mutants of a
      multidrug-susceptible standard strain of Salmonella enterica serovar Typhimurium
      (Salmonella Typhimurium) was constructed in our previous study. MICs of colistin
      were determined by the 2-fold serial broth microdilution method. Time-kill and
      survival assays were carried out with various concentrations of colistin. Growth
      curves and starvation survival were measured by OD600 or cfu count in LB and M9
      glucose (0.2%) minimum media. Quantitative RT-PCR was used to determine the mRNA
      expression levels of target genes. Results: The results showed that the MIC of
      colistin for the CpxR-overexpressed strain JSDeltaacrBDeltacpxR::kan/pcpxR was
      dramatically decreased (0.05 mg/L) by 16-fold compared with JS (0.8 mg/L) and
      JSDeltaacrBDeltacpxR::kan (0.8 mg/L). Colistin time-kill and survival assays
      showed that JSDeltaacrBDeltacpxR::kan/pcpxR was more susceptible to colistin
      (0.05 mg/L), but had a considerably higher survivability regarding prolonged
      starvation stress compared with JSDeltaacrBDeltacpxR::kan. Furthermore, the
      expression levels of colistin resistance-related genes (phoP, phoQ, pmrB, pmrC,
      pmrH and pmrD) were found to be remarkably down-regulated and the negative
      regulatory protein mgrB was significantly up-regulated. Conclusions: This study
      demonstrated that CpxR may regulate the colistin susceptibility of Salmonella
      Typhimurium through the PmrAB and PhoPQ regulatory systems.

PMID- 30107571
TI  - Genetic approach to select against embryo mortality caused by Enterococcus
      faecalis infection in laying hens.
AB  - Selection to reduce susceptibility to Enterococcus faecalis infection in laying
      hens may contribute to the prevention of amyloid arthropathy since it is mainly
      induced by this bacterium. Therefore, the aim of the present study was to
      investigate the possibility to select more laying hens that are resistant against
      E. faecalis infection through the embryo lethality assay (ELA), which is proposed
      as an alternative model to replace the adult avian challenge assay. Ten-day-old
      embryos of 500 Lohmann Brown layers were inoculated into the allantoic cavity
      with an infectious dose of 2.5 colony-forming units (cfu)/mL of the avian E.
      faecalis strain K923/96 in 3 ELAs. The embryonic mortality rate (EMR) was
      determined by candling the eggs daily over a period of 4 d. The average EMR
      estimated during the 3 ELAs was 50% and the highest EMR occurred 3 to 4 d post
      inoculation. The estimated heritability for embryonic survivability to the
      infection was h2 = 0.12-0.14, calculated with the logistic and probit link
      function, respectively, indicating that the selection of more laying hens that
      are resistant to E. faecalis infection is feasible. A highly negative genetic
      correlation was estimated between embryonic survivability and laying performance
      at the peak of lay (rg = -0.22) and at the end of the production (rg = -0.65), as
      well as with breaking strength (rg = -0.30 to -0.37). A positive correlation was
      found between egg weight and the embryonic survivability (rg = +0.16), and no
      genetic correlation was found with body weight and dynamic stiffness. Therefore,
      although it was demonstrated that it is possible to breed for E. faecalis
      resistance, special care should be taken to monitor and to take all traits and
      their genetic correlations into account in order to achieve a balanced genetic
      progress. Besides, the ELA does not require that the hens are exposed to
      pathogens thereby saving labor and cost. Therefore, it could be feasible that ELA
      be implemented in selection programs.

PMID- 30107572
TI  - The effect of childhood deprivation on weight status and mental health in
      childhood and adolescence: longitudinal findings from the Millennium Cohort
      Study.
AB  - Background: The study aims were to: (i) examine associations between deprivation
      at age 7 and health outcomes at age 7 and 14, (ii) determine whether a
      deprivation gradient to health outcomes exists at age 7 and 14, and (iii) assess
      the extent to which health outcomes at age 7 are associated with health outcomes
      at age 14. Methods: Data were from wave four and six of the Millennium Cohort
      Study. Health outcome measures were weight status, and Strengths and Difficulties
      Questionnaire measured mental health problems. Deprivation was determined using
      the 2004 English Indices of Multiple Deprivation. Adjusted logistic and
      multinomial logistic regressions were conducted. Results: A total of 6109
      children (1890 girls) had complete data. Overweight, obesity and mental health
      problems were greatest among children in the highest deprivation decile at age 7
      and 14 (P < 0.001). Health outcomes at age 7 were significantly associated with
      health outcomes at age 14 (P < 0.001). Conclusions: A marked social gradient to
      weight status and mental health was evident at age 7 and 14, and no evidence of
      equalization was found. Weight status and mental health in childhood is strongly
      associated with weight status and mental health in adolescence.

PMID- 30107573
TI  - Development and Validation of the School Refusal Evaluation Scale for
      Adolescents.
AB  - Objective: School refusal (SR) is considered as a clinical form of emotionally
      based school absenteeism related to the experience of strong negative emotions
      when attending school. However, there are no psychometrically sound measures
      specifically designed to assess SR. The aim of the present research was to
      develop and validate a multidimensional self-report measure of SR: the SChool
      REfusal EvaluatioN Scale (SCREEN) for adolescents. Methods: Two studies were
      performed to develop this scale. Study 1 used content analysis on 42 semi
      directed interviews to identify and organize the indicators of SR and to generate
      items. The item pool was then reviewed by experts to construct a pilot scale.
      Study 2 examined the psychometric properties of this pilot scale of the SCREEN in
      a community sample of 649 French adolescents (age: 10-16 years) and a clinical
      sample of 31 adolescents. Results: The initial SCREEN structure was identified
      via exploratory factor analysis, and the resultant model was validated using
      confirmatory factor analysis. In its final version (an 18-item, four-factor
      measurement model), the SCREEN reliably measures four interrelated aspects of SR.
      Data suggest good reliability and validity of scores on this SR measure. Results
      of the receiver operating characteristic (ROC) curve analysis indicated good
      accuracy of the SCREEN (sensitivity = .94 and specificity = .88). Conclusions:
      The SCREEN offers a new and valid measure to assess SR in research and clinical
      settings.

PMID- 30107574
TI  - Sustainable floor type for managing turkey production in a hot climate.
AB  - Floor type management is an important factor in turkey production in hot climates
      exceeding 30 degrees C. In this study, a total of 360 turkeys aged 4 wk were
      randomly distributed to investigate growth performance, carcass characteristics,
      certain health aspects (breast blisters score, footpad burns, hock discoloration,
      and plumage condition), and airborne conditions. Birds in the first group were
      raised on a littered floor (control; C), whereas birds in the other groups (T1,
      T2, T3, T4, and T5) were raised on cement, wire net, rubber mat, plastic and
      wooden slatted floors, respectively. The results indicated that growth
      performance and meat quality were improved, with increases in body weight, daily
      body weight gain, feed conversion ratio, and tenderness and juiciness values,
      when plastic and wooden slatted floors were used. Moreover, the use of plastic
      and wooden slatted floors attenuated body temperature, airborne dust
      particulates, and ammonia concentrations. In conclusion, placing plastic, wooden
      slatted, or wire floors reduced the incidence of health disorders and alleviated
      heat stress effects by decreasing body temperature and the heterophil to
      lymphocyte ratio. Thus, plastic and wooden slatted floors are suitable for
      growing turkeys under the conditions of this study.

PMID- 30107575
TI  - The patient safety culture: a systematic review by characteristics of Hospital
      Survey on Patient Safety Culture dimensions.

PMID- 30107569
TI  - Bacterial type III secretion systems: a complex device for the delivery of
      bacterial effector proteins into eukaryotic host cells.
AB  - Virulence-associated type III secretion systems (T3SS) serve the injection of
      bacterial effector proteins into eukaryotic host cells. They are able to secrete
      a great diversity of substrate proteins in order to modulate host cell function,
      and have evolved to sense host cell contact and to inject their substrates
      through a translocon pore in the host cell membrane. T3SS substrates contain an N
      terminal signal sequence and often a chaperone-binding domain for cognate T3SS
      chaperones. These signals guide the substrates to the machine where substrates
      are unfolded and handed over to the secretion channel formed by the transmembrane
      domains of the export apparatus components and by the needle filament. Secretion
      itself is driven by the proton motive force across the bacterial inner membrane.
      The needle filament measures 20-150 nm in length and is crowned by a needle tip
      that mediates host-cell sensing. Secretion through T3SS is a highly regulated
      process with early, intermediate and late substrates. A strict secretion
      hierarchy is required to build an injectisome capable of reaching, sensing and
      penetrating the host cell membrane, before host cell-acting effector proteins are
      deployed. Here, we review the recent progress on elucidating the assembly,
      structure and function of T3SS injectisomes.

PMID- 30107576
TI  - Prospective validation of the Juvenile Spondyloarthritis Disease Activity Index
      in children with enthesitis-related arthritis.
AB  - Objective: To measure disease activity in children with enthesitis-related
      arthritis the Juvenile Spondyloarthritis Disease Activity Index (JSpADA) was
      developed and retrospectively validated. We prospectively validated JSpADA and
      also assessed performance of adult SpA scores. Methods: Children with enthesitis
      related arthritis (ILAR criteria) less than 18 years of age were enrolled.
      Baseline characteristics and different disease activity measures (JSpADA, BASDAI,
      Ankylosing Spondylitis Disease Activity Score-ESR, juvenile arthritis DAS-10
      joints), and Childhood HAQ, physician global assessment and patient global
      assessment were recorded at baseline. In some children follow-up was also done.
      Results: The mean (s.d.) age of 127 children (116 boys) was 14.3 (2.4) years and
      disease duration was 36.9 (3) months. Ninety of 104 (86.5%) children were HLA-B27
      positive. JSpADA showed high correlation with physician global assessment (r =
      0.87; P < 0.0001), patient global assessment (r = 0.80, P < 0.0001), juvenile
      arthritis DAS-10 joints (r = 0.89; P < 0.0001) and Childhood HAQ (r = 0.83, P <
      0.0001). The JSpADA scores showed good internal consistency, discriminative
      validity and sensitivity to change. In 15% of children back mobility could not be
      tested due to active arthritis in lower limbs. The 7-variable JSpADA excluding
      back mobility performed as well as the original JSpADA. Adult scores showed good
      construct validity, discriminative capacity and sensitivity to change, and had
      good correlation with JSpADA (BASDAI, r = 0.84; Ankylosing Spondylitis Disease
      Activity Score-ESR, r = 0.84). Conclusion: JSpADA is a valid score for measuring
      disease activity in enthesitis-related arthritis. Adult scores also performed
      well. Excluding back mobility needs to be assessed in future to improve JSpADA
      performance.

PMID- 30107577
TI  - The Risk of Elective Abortion in Women With Crohn's Disease and Ulcerative
      Colitis: A Nationwide Cohort Study.
AB  - Backgroud: Women with inflammatory bowel disease (IBD) might have an increased
      tendency to choose an elective abortion due to a fear that their fetus could be
      harmed by use of medications, disease flares during pregnancy, or for genetic
      reasons. We examined the risk of elective abortions in women with ulcerative
      colitis (UC) and Crohn's disease (CD) compared with women without IBD. Methods:
      This nationwide cohort study, based on Danish health registries, comprises all
      registered pregnancies from 1996 through 2015. The 2 exposed groups constituted
      pregnancies of women with UC or CD, and the unexposed group constituted all
      pregnancies of women without IBD. Our outcome was elective abortion by maternal
      request up until the end of the 12th completed week of gestation. We used
      logistic regression models and calculated the odds ratio (OR) for an elective
      abortion, controlling for confounders. Results: The overall prevalence rates of
      elective abortions in women with UC and CD and without IBD were 12.4% (898
      elective abortions/7250 pregnancies), 14.9% (978 elective abortions/6559
      pregnancies), and 16.9% (285,251 elective abortions/1,691,857 pregnancies),
      respectively. In women with UC and CD, the adjusted ORs for an elective abortion
      (95% confidence interval) were 0.80 (0.74-0.86) and 0.96 (0.89-1.04),
      respectively. Conclusions: Pregnant women with IBD are not more likely to choose
      an elective abortion compared with women without IBD. These results are
      reassuring as they suggest that women with IBD are not so worried about a
      negative impact of their disease, disease activity, or medications that they
      would choose to terminate a pregnancy.

PMID- 30107578
TI  - Laboratory Investigation of Cauliflower-Fungus-Insect Interactions for Cabbage
      Maggot Control.
AB  - The cabbage maggot (also known as cabbage root fly [CRF]; Delia radicum L.) is a
      serious pest of brassicas. The pest's soil-dwelling larvae are especially
      damaging to young brassica transplants. In light of toxic soil insecticide phase
      out novel biocontrol management solutions are sought for. Our research is focused
      on the development of a biological control strategy involving cauliflower
      plantlet inoculation with insect pathogenic fungi. This article presents the
      results of a laboratory investigation of cauliflower * microbe * CRF
      interactions. Seven isolates of fungi (entomopathogenic and rhizosphere-competent
      fungi and soil saprotrophs) were tested for their pathogenicity to CRF and their
      effects on cauliflower plantlets. The laboratory experiments were performed in
      sterilized substrate. Several strains significantly increased CRF mortality, some
      at par with a commercial bioinsecticide based on B. bassiana (Balsamo-Crivelli)
      Vuillemin (Hypocreales: Cordycipitaceae). All strains colonized the rhizoplane,
      however to varying extent. Some isolates were also reisolated from within healthy
      plant tissues and thus identified as endophytes. The method of applying conidia
      had a significant effect on survival and weight of seedlings and rhizoplane and
      endophytic colonization rates. Two Metarhizium brunneum Petsch (Hypocreales:
      Clavicipitaceae) isolates exhibited plant growth promotion effects when
      ungerminated seeds were coated with conidia. The ecological implications of plant
      * microbe * pest interactions and options for improving the effectiveness of a
      fungal-based biological CRF management strategy are discussed.

PMID- 30107579
TI  - Wolbachia's role in mediating its flea's reproductive success differs according
      to flea origin.
AB  - Endosymbionts-microbes that live within and engage in prolonged and intimate
      associations with their hosts-are gaining recognition for their direct impact on
      plant and animal reproduction. Here we used the overlooked Wolbachia-flea system
      to explore the possibility that endosymbionts may also play a role as mediators
      in shaping the reproductive success of their hosts. We simultaneously quantified
      the Wolbachia density in field- and laboratory-originated fleas that fed and
      mated on rodents for either 5 or 10 days and assessed their body size and current
      reproductive success. By combining multigroup analysis and model selection
      approaches, we teased apart the contribution of the direct effects of the flea's
      physiological age and body size and the mediation effect of its Wolbachia
      endosymbionts on flea reproductive success, and we showed that the latter was
      stronger than the former. However, interestingly, the mediation effect was
      manifested only in laboratory-originated fleas, for which the increase in
      Wolbachia with age translated into lower reproductive success. These results
      suggest that some well-supported phenomena, such as aging effects, may be driven
      by endosymbionts and show once again that the role of endosymbionts in shaping
      the reproductive success of their host depends on their selective environment.

PMID- 30107580
TI  - Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for
      Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade
      Gliomas?
AB  - BACKGROUND: Approximately 20% of low-grade gliomas (LGG) display visible
      protoporphyrin fluorescence during surgery after 5-aminolevulinic acid (5-ALA)
      administration. OBJECTIVE: To determine if fluorescence represents a prognostic
      marker in LGG. METHODS: Seventy-four consecutive patients with LGG (World Health
      Organization 2016) were operated on with 5-ALA. Fluorescent tissue was
      specifically biopsied. Tumor size, age, Karnofsky index, contrast-enhancement,
      fluorescence, and molecular factors (IDH1/IDH2-mutations, Ki67/MIB1 Index, 1p19q
      codeletions, ATRX, EGFR, p53 expression, and O6-methylguanine DNA
      methyltransferase promotor methylation), were related to progression-free
      survival (PFS), malignant transformation-free survival (MTFS) and overall
      survival (OS). RESULTS: Sixteen of seventy-four LGGs (21.6%) fluoresced.
      Fluorescence was partially related to weak enhancement on magnetic resonance
      imaging and increased (positron emission tomography)PET-FET uptake, but not to
      Karnofsky Performance Score, tumor size, or age. Regarding molecular markers,
      only EGFR expression differed marginally (fluorescing vs nonfluorescing: 19% vs
      5%; P = .057). Median follow-up was 46.4 mo (95% confidence interval [CI]: 41.8
      51.1). PFS, MTFS, and OS were shorter in fluorescing tumors (PFS: median 9.8 mo,
      95% CI: 1.00-27.7 vs 45.8, 31.9-59.7, MTFS: 43.0 [27.5-58.5] vs 64.6 [57.7-71.5],
      median not reached, P = .015; OS: 51.6, [34.8-68.3] vs [68.2, 62.7-73.8], P =
      .002). IDH mutations significantly predicted PFS, MTFS, and OS. In multivariate
      analysis IDH status and fluorescence both independently predicted MTFS and OS.
      PFS was not independently predicted by fluorescence. CONCLUSION: This is the
      first report investigating the role of ALA-induced fluorescence in histologically
      confirmed LGG. Fluorescence appeared to be a marker for inherent malignant
      transformation and OS, independently of known prognostic markers. Fluorescence in
      LGG might be taken into account when deciding on adjuvant therapies.

PMID- 30107582
TI  - Lateral Transorbital Versus Endonasal Transpterygoid Approach to the Lateral
      Recess of the Sphenoid Sinus-A Comparative Anatomic Study.
AB  - BACKGROUND: The treatment of cerebrospinal fluid leaks of the lateral recess of
      the sphenoid sinus (LRSS) faces difficulties due to the deep location of the
      osseous defect. When treated with craniotomies, brain retraction is a concern.
      The endoscopic endonasal transpterygoid approach (EETA) is a direct and less
      invasive procedure; however, it may require transection of the vidian nerve (VN).
      OBJECTIVE: To investigate the feasibility of a lateral transorbital approach
      (LTOA) as an alternative pathway to the LRSS that avoids VN sacrifice. METHODS:
      Six embalmed heads with well-pneumatized LRSS were preselected by inspecting
      their computed tomography scans. One LTOA and one EETA were performed on 1 side
      of each specimen. The approaches were compared regarding working distance and
      neurovascular structures being sacrificed. The working area of the LTOA was also
      measured. RESULTS: The average working distances were 59.9 (+/-2.94) mm for the
      LTOA and 76.4 (+/-3.99) mm for the EETA (P < .001). The LTOA generated a working
      area with a diameter of 9 to 14 mm. The EETA demanded the sacrifice of VN and the
      sphenopalatine artery in all specimens to expose the LRSS. No neurovascular
      structures were found in the trajectory of the LTOA. CONCLUSION: The LTOA to the
      LRSS is feasible, with minimal risk of injuring neurovascular structures. It
      offers a shorter pathway when compared to the EETA. Although the LTOA provides no
      options for vascularized flap reconstruction, it allows immediate access to
      muscle grafts. The LTOA may serve as an alternative to treating cerebrospinal
      fluid leaks of the LRSS.

PMID- 30107581
TI  - Activity and structure of EcoKMcrA.
AB  - Escherichia coli McrA (EcoKMcrA) acts as a methylcytosine and
      hydroxymethylcytosine dependent restriction endonuclease. We present a
      biochemical characterization of EcoKMcrA that includes the first demonstration of
      its endonuclease activity, small angle X-ray scattering (SAXS) data, and a
      crystal structure of the enzyme in the absence of DNA. Our data indicate that
      EcoKMcrA dimerizes via the anticipated C-terminal HNH domains, which together
      form a single DNA binding site. The N-terminal domains are not homologous to SRA
      domains, do not interact with each other, and have separate DNA binding sites.
      Electrophoretic mobility shift assay (EMSA) and footprinting experiments suggest
      that the N-terminal domains can sense the presence and sequence context of
      modified cytosines. Pyrrolocytosine fluorescence data indicate no base flipping.
      In vitro, EcoKMcrA DNA endonuclease activity requires Mn2+ ions, is not strictly
      methyl dependent, and is not observed when active site variants of the enzyme are
      used. In cells, EcoKMcrA specifically restricts DNA that is modified in the
      correct sequence context. This activity is impaired by mutations of the nuclease
      active site, unless the enzyme is highly overexpressed.

PMID- 30107583
TI  - Effects of dietary cottonseed oil and cottonseed meal supplementation on the
      structure, nutritional composition of egg yolk and gossypol residue in eggs.
AB  - The aim of this study was to evaluate the effects of dietary non-gossypol
      cottonseed oil (CSO) or cottonseed meal (CSM) and their interactions on the
      texture properties, structure, nutritional composition, and edible safety of egg
      yolk. A total of 162 24-wk-old Hy-line Brown laying hens were randomly allocated
      into 9 diet treatments with 6 replicates of 3 hens per cage. A 3 * 3 factorial
      design using corn soybean meal-based diets supplemented with 0, 6, or 12% CSM and
      0, 2, or 4% CSO in place of soybean meal and soybean oil, respectively, was
      utilized. The experiment lasted for 8 wk. Eggs obtained from the CSO groups had
      an egg yolk gel structure, and the hardness of egg yolk increased significantly
      (P < 0.001) after 4 degrees C storaged for 2 wk; the texture properties of eggs
      storage at 25 degrees C had opposite trend. There were no differences in texture
      properties of fresh egg yolk among the different groups (P > 0.05). The saturated
      fatty acid (SFA) content of egg yolk increased in a CSO dose-dependent manner,
      whereas opposite effects (P < 0.001) were found in the monounsaturated fatty
      acids (MUFA) and the omega-3/omega-6 fatty acid ratio. CSO-containing diets
      significantly reduced the cholesterol content (P < 0.05). No significant
      difference was observed among the different groups on the contents of moisture,
      crude protein, crude fat, phospholipid, potassium, or iron (P > 0.05) in the egg
      yolk. Total gossypol residues were increased with the increased amount of CSM (P
      < 0.05), and these changes were independent of time (P > 0.05). The total
      gossypol concentration in the yolk was 2.01 to 5.16 mg/kg. These results suggest
      that CSO has a key influence on egg yolk quality, reducing both its taste and
      nutritional value. Egg yolk gelation was significantly associated with the change
      of fatty acid composition caused by CSO and storage conditions. Free gossypol
      will remain in the egg yolk. Although the residue is low, the edible safety risk
      of eggs maybe exists.

PMID- 30107585
TI  - Vitamin D Status Is Not Associated with Risk of Early Menopause.
AB  - Background: Early natural menopause, the cessation of ovarian function before age
      45 y, is positively associated with cardiovascular disease and other conditions.
      Dietary vitamin D intake has been inversely associated with early menopause;
      however, no previous studies have evaluated risk with regard to plasma 25
      hydroxyvitamin D [25(OH)D] concentrations. Objective: We prospectively evaluated
      associations of total and free 25(OH)D and vitamin D-binding protein (VDBP)
      concentrations and the risk of early menopause in a case-control study nested
      within the Nurses' Health Study II (NHS2). We also considered associations of
      25(OH)D and VDBP with anti-Mullerian hormone (AMH) concentrations. Methods: The
      NHS2 is a prospective study in 116,430 nurses, aged 25-42 y at baseline (1989).
      Premenopausal plasma blood samples were collected between 1996 and 1999, from
      which total 25(OH)D and VDBP concentrations were measured and free 25(OH)D
      concentrations were calculated. Cases experienced menopause between blood
      collection and age 45 y (n = 328) and were matched 1:1 by age and other factors
      to controls who experienced menopause after age 48 y (n = 328). Conditional
      logistic regression models were used to estimate ORs and 95% CIs for early
      menopause according to each biomarker. Generalized linear models were used to
      estimate AMH geometric means according to each biomarker. Results: After
      adjusting for smoking and other factors, total and free 25(OH)D were not
      associated with early menopause. Quartile 4 compared with quartile 1 ORs were
      1.04 (95% CI: 0.60, 1.81) for total 25(OH)D and 0.70 (95% CI: 0.41, 1.20) for
      free 25(OH)D. 25(OH)D was unrelated to AMH concentrations. VDBP was positively
      associated with early menopause; the OR comparing the highest with the lowest
      quartile of VDBP was 1.80 (95% CI: 1.09, 2.98). Conclusions: Our findings suggest
      that total and free 25(OH)D are not importantly related to the risk of early
      menopause. VDBP may be associated with increased risk, but replication is
      warranted.

PMID- 30107584
TI  - Protein synthesis levels are increased in a subset of individuals with fragile X
      syndrome.

PMID- 30107586
TI  - Using a social marketing approach to develop Healthy Me, Healthy We: a nutrition
      and physical activity intervention in early care and education.
AB  - Although social marketing principles have been successfully employed in school
      based interventions to prevent obesity, use in early care and education (ECE)
      settings has been limited. This paper describes the use of the social marketing
      approach to develop an ECE-based intervention that encourages an ECE provider
      parent partnership to improve the quality of preschool children's diets and their
      level of physical activity. A six-step social marketing approach for public
      health interventions guided the development of this ECE-based intervention. These
      steps were as follows: (i) initial planning, (ii) formative research, (iii)
      strategy development, (iv) program development, (v) implementation, and (vi)
      monitoring and evaluation. During this process, we reviewed current literature,
      conducted focus groups with ECE providers and parents, developed a detailed
      conceptual model and content map, created and tested the campaign concept, and
      developed final campaign materials along with strategies for its implementation.
      The final intervention resulting from this process was an 8-month campaign known
      as Healthy Me, Healthy We. The campaign is delivered by the child care center and
      includes branded materials for use in the classroom and at home. The final
      campaign is being evaluated in a cluster-randomized trial. Healthy Me, Healthy We
      offers an innovative approach to promoting healthy eating and physical activity
      during early childhood, a key developmental period, that leverages partnership
      between ECE providers and parents to affect behavior change.

PMID- 30107587
TI  - Outbreaks of Serratia marcescens and Serratia rubidaea bacteremia in a central
      Kathmandu hospital following the 2015 earthquakes.
AB  - Background: Human infections with Serratia spp. are generally limited to Serratia
      marcescens and the Serratia liquefaciens complex. There is little data regarding
      the infections caused by the remaining Serratia spp., as they are seldom isolated
      from clinical specimens. Methods: In this health care setting in Kathmandu, Nepal
      routine blood culture is performed on all febrile patients with a temperature >38
      degrees C or when there is clinical suspicion of bacteremia. During 2015 we
      atypically isolated and identified several Serratia spp. We extracted clinical
      data from these cases and performed whole genome sequencing on all isolates using
      a MiSeq system (Ilumina, San Diego, CA, USA). Results: Between June and November
      2015, we identified eight patients with suspected bacteremia that produced a
      positive blood culture for Serratia spp., six Serratia rubidaea and five Serratia
      marcescens. The S. rubidaea were isolated from three neonates and were
      concentrated in the neonatal intensive care unit between June and July 2015. All
      patients were severely ill and one patient died. Whole genome sequencing
      confirmed that six Nepalese S. rubidaea sequences were identical and indicative
      of a single-source outbreak. Conclusions: Despite extensive screening we were
      unable to identify the source of the outbreak, but the inferred timeline
      suggested that these atypical infections were associated with the aftermath of
      two massive earthquakes. We speculate that deficits in hygienic behavior,
      combined with a lack of standard infection control, in the post-earthquake
      emergency situation contributed to these unusual Serratia spp. outbreaks.

PMID- 30107588
TI  - End-of-life care for cancer patients in Japanese acute care hospitals: A
      nationwide retrospective administrative database survey.
AB  - Background: End-of-life (EOL) cancer care in Japanese acute care hospitals has
      not been well described. Methods: We aimed to assess the aggressiveness of EOL
      care and examine common treatments administered to cancer patients using a health
      administrative database. Subjects are adult cancer patients who died at acute
      care hospitals between April 2011 and March 2014. Data from the Japanese
      Diagnosis Procedure Combination database were analysed to measure the
      aggressiveness of care (chemotherapy, intensive care unit [ICU] admission and
      cardiopulmonary resuscitation [CPR]) and describe procedures and prescriptions
      administered in the last 14 and 30 days of life, disaggregated by hospital case
      volume: high, intermediate and low volumes. Results: Of 248,978 cancer decedents,
      170,024 died in high-, 70,231 in intermediate- and 8,723 in low-volume hospitals.
      Aggressive treatment in the last 14 days of life included chemotherapy (9.4%,
      7.3%, and 5.4%, respectively), ICU admission (3.0%, 2.0%, and 2.4%) and CPR
      (5.8%, 6.4%, and 8.3%). Opioids were administered to 66.0%, 59.0% and 49.4%
      patients, while Palliative Care Team intervention was performed for 8.5%, 2.2%
      and 2.0% of patients, respectively in the last 30 days. In high-volume hospitals,
      radiotherapy and certified outpatient chemotherapy fees were more frequent.
      Catecholamines and hyperalimentation were more frequently administered in low
      volume hospitals. Conclusion: This is the first study to assess EOL care among
      Japanese acute care hospitals. More frequent use of chemotherapy at high-volume
      hospitals may reflect a well-established cancer treatment system. The approach
      for low-volume hospitals might improve the EOL care for all cancer patients in
      Japan.

PMID- 30107589
TI  - Additivity of apparent and standardized ileal digestibility of amino acid
      determined by chromic oxide and titanium dioxide in mixed diets containing wheat
      and multiple protein sources fed to growing pigs.
AB  - The aim of this study was to investigate the additivity of apparent ileal
      digestibility (AID) and standardized ileal digestibility (SID) of crude protein
      (CP) and amino acids (AA) in mixed diets containing wheat, canola meal (CM), meat
      and bone meal (MBM), and sorghum distillers' dried grains with solubles (DDGS)
      fed to pigs with chromic oxide (Cr2O3) and titanium dioxide (TiO2) as
      digestibility index markers. Four diets were prepared to contain wheat, CM, MBM,
      or DDGS as a sole source of nitrogen; three mixed diets were prepared to contain
      wheat, CM, and MBM; wheat, MBM, and DDGS; or wheat, CM, MBM, and DDGS; also, a
      nitrogen-free diet was prepared to estimate the basal ileal endogenous losses
      (BEL) of CP and AA. Both Cr2O3 and TiO2 were incorporated at 5 g/kg into each
      diet. Sixteen barrows (initial body weight = 34.7 +/- 0.6 kg) surgically fitted
      with T-cannulas at the distal ileum were allotted to a duplicate 8 * 4 Youden
      square design with eight experimental diets and four periods. During each 7-d
      period, the ileal digesta was collected for 2 d after a 5-d adaptation, and the
      AID and SID of CP and AA were determined using Cr2O3 or TiO2 as marker. There was
      no interaction between diet and marker type for both AID and SID of CP and AA.
      Similar BEL, AID, and SID of CP and AA were determined by Cr2O3 and TiO2. In the
      wheat-CM-MBM diet, the measured AID of CP and most AA determined with Cr2O3 or
      TiO2 were not different from the predicted values, which was determined based on
      the measured AID values in wheat, CM, and MBM. In the wheat-MBM-DDGS diet, the
      measured and predicted AID of CP and seven indispensable AA differed (P < 0.05)
      using Cr2O3 as marker, and the measured and predicted AID of CP and four
      indispensable AA differed (P < 0.05) using TiO2 as marker. The measured AID of CP
      and most indispensable AA were greater (P < 0.05) than predicted AID regardless
      of marker type for the wheat-CM-MBM-DDGS diet. The measured SID of CP and
      indispensable AA were consistent with the predicted values, except Lys in the
      wheat-CM-MBM diet using either marker and His in the wheat-MBM-DDGS diet with
      Cr2O3 as marker. In conclusion, more accurate prediction of ileal digestibility
      of CP and AA was achieved using SID rather than AID in mixed diets containing
      wheat, CM, MBM, and DDGS. The determination of endogenous loss, AID, and SID of
      CP and AA were not affected by marker type in this study. In addition, the
      additivity of AID and SID of CP and most indispensable AA in mixed diets was not
      affected by marker type.

PMID- 30107590
TI  - MERS: What is the current situation in Saudi Arabia?

PMID- 30107591
TI  - Validation of the Musculoskeletal Health Questionnaire in inflammatory arthritis:
      a psychometric evaluation.
AB  - Objectives: The Musculoskeletal Health Questionnaire (MSK-HQ) is a recently
      developed Patient Reported Outcome Measure for use across patients with
      musculoskeletal conditions. This study provides a validation of the MSK-HQ
      examining construct validity and reliability in inflammatory arthritis. Methods:
      287 adults with inflammatory arthritis completed the MSK-HQ and other Patient
      Reported Outcome Measures at baseline and after 3 months. Construct validity was
      assessed using item response theory methods. Concurrent validity was considered
      in relation to the HAQ and EuroQol-5D in all patients, as well as the RA Impact
      of Disease (RAID), PsA Impact of Disease scales, and AS Quality of Life
      Questionnaire (ASQoL) in disease subtypes. Results: The MSK-HQ was approximately
      normally distributed with no evidence of floor or ceiling effects. A
      unidimensional structure was confirmed. Two items were less weakly related to the
      latent musculoskeletal health variable, providing some evidence of
      multidimensionality. Reliability was high (alpha = 0.93). The total score
      correlated highly with the HAQ (r = -0.81) and EuroQol-5D index (r = 0.80) in all
      patients, RAID in RA patients (r = -0.88), PsA Impact of Disease in PsA patients
      (r = -0.88), and ASQoL in AS patients (r = -0.86). Test-retest reliability was
      high (rICC = 0.73). Conclusion: This study provides evidence for the validity and
      reliability of the MSK-HQ in people with inflammatory arthritis. The major
      advantage of the MSK-HQ is that it is not disease specific and has high content
      validity in rheumatological conditions. The MSK-HQ score will be of value in
      clinical rheumatology practice, providing a measure that can be used across
      disease areas.

PMID- 30107592
TI  - Dissecting KMT2D missense mutations in Kabuki syndrome patients.
AB  - Kabuki syndrome is a rare autosomal dominant condition characterized by facial
      features, various organs malformations, postnatal growth deficiency and
      intellectual disability. The discovery of frequent germline mutations in the
      histone methyltransferase KMT2D and the demethylase KDM6A revealed a causative
      role for histone modifiers in this disease. However, the role of missense
      mutations has remained unexplored. Here, we expanded the mutation spectrum of
      KMT2D and KDM6A in KS by identifying 37 new KMT2D sequence variants. Moreover, we
      functionally dissected 14 KMT2D missense variants, by investigating their impact
      on the protein enzymatic activity and the binding to members of the WRAD complex.
      We demonstrate impaired H3K4 methyltransferase activity in 9 of the 14 mutant
      alleles and show that this reduced activity is due in part to disruption of
      protein complex formation. These findings have relevant implications for
      diagnostic and counseling purposes in this disease.

PMID- 30107593
TI  - Age Effects in Sequence-Construction for a Continuous Cognitive Task: Similar
      Sequence-Trends but Fewer Switch-Points.
AB  - OBJECTIVES: Many real-life settings require decision-makers to sort a pre
      determined set of outcomes or activities into a preferred sequence, and people
      vary in whether they prefer to tackle the most challenging aspects first, leave
      them for the last, or intersperse them with less challenging outcomes. Prior
      research on age differences in sequence-preferences has focused on discrete and
      hypothetical events. The present study expands this work by examining sequence
      preferences for a realistic, continuous, sustained, and cognitively challenging
      task. METHODS: Participants (N=121, aged 21-86) were asked to complete 10 minutes
      of a difficult cognitive task (2-back), 10 minutes of an easy cognitive task (1
      back), and 10 minutes of rest over the course of a 30-minute interval. They could
      complete the tasks in any order and switch tasks as often as they wished and they
      were rewarded for correct performance. Additional measures included affective and
      physiological responses, task accuracy, time-perspective, and demographics.
      RESULTS: The majority of participants constructed sequences with decreasing task
      difficulty. Preferences for the general trend of the sequence were not
      significantly related to age, but the number of switches among the tasks
      decreased with age, and task-switching tended to incur greater accuracy
      decrements among older as compared to younger adults. DISCUSSION: We address
      potential methodological concerns, discuss theoretical implications, and consider
      potential real-life applications.

PMID- 30107594
TI  - King Caz: Cazenove, Thatcherism, and the 1980s financial revolution.
AB  - This article shows how elite stockbrokers Cazenove and Co. responded to the 'Big
      Bang' deregulation of the financial sector in 1986, using social networks and
      inherited practices to navigate an ostensibly technical and modernizing
      revolution. The Thatcher administration's reform of the London Stock Exchange was
      an economic enterprise intended to end restrictive practices and open the City to
      competition. A more open meritocratic financial sector marked the 'death of
      gentlemanly capitalism' and coalesced with a political agenda for
      entrepreneurialism and popular capitalism. Yet this case study shows how
      Cazenove's culture drove its strategy, that privilege and hierarchy were
      sustained by influential cross-sector networks, and that there was resistance to
      change, even though technological change and new financial instruments were
      embraced as part of a strategy which mixed innovation with tradition.
      Essentially, elite networks persisted in the 1980s deregulated economy, as
      established relationships were used to optimum effect and became more important
      after Big Bang. A more mutually supportive relationship between finance and
      industry than has hitherto been imagined is also demonstrated. By showing how a
      modernizing revolution was navigated using social networks and traditions, this
      article restores the role of culture to financial history. It also contributes to
      a body of work in twentieth-century British history which challenges the
      perception that neoliberal ideas were consistently applied under Thatcherism and
      complicates the notion of a coherent Thatcherite project.

PMID- 30107596
TI  - Clinical and Genomic Features of the First Cases of Elizabethkingia anophelis
      Infection in New York, Including the First Case in a Healthy Infant Without
      Previous Nosocomial Exposure.
AB  - Elizabethkingia spp are Gram-negative bacteria associated with neonatal
      meningitis. In 2015-2016, an outbreak of Elizabethkingia anophelis infection that
      involved 63 patients and 18 deaths occurred in Wisconsin. Despite a multistate
      investigation, as of September 2016 the source remained undetermined, and experts
      warned of reemergence. We describe here the first cases of E anophelis infection
      in New York, including the case of a healthy infant without previous healthcare
      contact.

PMID- 30107595
TI  - The prevalence of co-morbidities and their impact on physical activity in people
      with inflammatory rheumatic diseases compared with the general population:
      results from the UK Biobank.
AB  - Objectives: To compare the prevalence and incidence of chronic co-morbidities in
      people with inflammatory rheumatic and musculoskeletal diseases (iRMDs), and to
      determine whether the prevalent co-morbidities are associated with physical
      activity levels in people with iRMDs and in those without iRMDs. Methods:
      Participants were recruited to the UK Biobank; a population-based cohort. Data
      were collected about demographics, physical activity, iRMDs (RA, PsA, AS, SLE)
      and other chronic conditions, including angina, myocardial infarction, stroke,
      hypertension, pulmonary disease, diabetes and depression. The standardized
      prevalence of co-morbidities in people with iRMDs was calculated. Cox regression
      was used to determine the relationship between the presence of an iRMD and an
      incident co-morbidity. The relationship between the presence (versus absence) of
      a (co-)morbidity and physical activity level (low, moderate, high) in people with
      iRMDs and in those without was assessed using multinomial logistic regression.
      Results: A total of 488 991 participants were included. The estimated prevalence
      of each co-morbidity was increased in participants with an iRMD, compared with in
      those without, particularly for stroke in participants with SLE (standardized
      morbidity ratio (95% CI), 4.9 (3.6, 6.6). Compared with people with no iRMD and
      no morbidity, the odds ratios (95% CI) for moderate physical activity were
      decreased for: no iRMD and morbidity, 0.87 (0.85, 0.89); iRMD and no co
      morbidity, 0.71 (0.64, 0.80); and iRMD and co-morbidity, 0.58 (0.54, 0.63).
      Conclusion: Having a (co-)morbidity is associated with reduced physical activity
      in the general population, and to a greater extent in participants with an iRMD.
      Optimal management of both iRMDs and co-morbidities may help to reduce their
      impact on physical activity.

PMID- 30107598
TI  - The "Cluster-SUNCT Syndrome": The Lumper-Splitter Problem.

PMID- 30107599
TI  - Tocilizumab in the treatment of severe and/or refractory vasculo-Behcet's
      disease: a single-centre experience in China.

PMID- 30107597
TI  - Voxel-wise radiogenomic mapping of tumor location with key molecular alterations
      in patients with glioma.
AB  - Background: This study aims to evaluate the impact of tumor location on key
      molecular alterations on a single voxel level in patients with newly diagnosed
      glioma. Methods: A consecutive series of n = 237 patients with newly diagnosed
      glioblastoma and n = 131 patients with lower-grade glioma was analyzed.
      Volumetric tumor segmentation was performed on preoperative MRI with a semi
      automated approach and images were registered to the standard Montreal
      Neurological Institute 152 space. Using a voxel-based lesion symptom mapping
      (VLSM) analysis, we identified specific brain regions that were associated with
      tumor-specific molecular alterations. We assessed a predefined set of n = 17
      molecular characteristics in the glioblastoma cohort and n = 2 molecular
      characteristics in the lower-grade glioma cohort. Permutation adjustment (n =
      1000 iterations) was used to correct for multiple testing, and voxel t-values
      that were greater than the t-value in >95% of the permutations were retained in
      the VLSM results (alpha = 0.05, power > 0.8). Results: Tumor location
      predilection for isocitrate dehydrogenase (IDH) mutant tumors was found in both
      glioblastoma and lower-grade glioma cohorts, each showing a concordant
      predominance in the frontal lobe adjacent to the rostral extension of the lateral
      ventricles (permutation-adjusted P = 0.021 for the glioblastoma and 0.013 for the
      lower-grade glioma cohort). Apart from that, the VLSM analysis did not reveal a
      significant association of the tumor location with any other key molecular
      alteration in both cohorts (permutation-adjusted P > 0.05 each). Conclusion: Our
      study highlights the unique properties of IDH mutations and underpins the
      hypothesis that the rostral extension of the lateral ventricles is a potential
      location for the cell of origin in IDH-mutant gliomas.

PMID- 30107600
TI  - Effects of IBDV infection on expression of ghrelin and ghrelin-related genes in
      chicken.
AB  - Ghrelin is a peptide hormone that plays a modulatory role in the immune system.
      Studies have demonstrated that mammal ghrelin level is influenced by pathological
      status. However, it has not been reported whether chicken ghrelin level changes
      during pathogen infection. This study was designed to investigate changes of
      ghrelin levels in chickens infected with infectious bursal disease virus (IBDV)
      and to explore the relationship between ghrelin changes and bursal damage, and
      inflammatory cells infiltration induced by IBDV. The results showed that (1)
      plasma ghrelin concentration increased after IBDV infection. It reached a peak at
      10443.6 +/- 2612.9 pg/mL on 2 dpi, which was about 100-fold as high as that of
      the control. Then it decreased sharply on 3 dpi, which was only 31.7% as that of
      2 dpi, and remained stable until 5 dpi. Meanwhile, ghrelin and ghrelin-related
      gene, ghrelin-o-acyltransferase (GOAT), and growth hormone secretagogue receptor
      (GHSR) mRNA expression levels in bursa were also increased after IBDV infection,
      and reached the peak on 2 dpi at 149, 28.8, and 117.2-fold higher than that of
      the control, respectively. Then they decreased and remained at a higher status.
      Correlation analysis showed that plasma ghrelin concentration and ghrelin, GOAT,
      and GHSR mRNA expressions in bursa were strongly associated with IBDV VP2 mRNA
      expression in bursa. (2) The damage of bursa was the most severe on 5 dpi with a
      histopathological score of 12. It had no direct correlation with plasma ghrelin
      level and ghrelin, GOAT, and GHSR mRNA expressions in bursa. However, the number
      of inflammatory cells infiltrating into bursa, which was the highest on 2 and 3
      dpi, showed significant a positive correlation with the ghrelin and GHSR mRNA
      expression. Presumably chicken ghrelin may function as an anti-inflammatory
      factor. In conclusion, IBDV infection upregulates the expression of ghrelin and
      ghrelin-related gene in chickens, and chicken ghrelin may play an important
      regulatory role during pathogen infection.

PMID- 30107601
TI  - Development of macrolide resistance in Bordetella bronchiseptica is associated
      with the loss of virulence.
AB  - Background: Why resistance to specific antibiotics emerges and spreads rapidly in
      some bacteria confronting these drugs but not others remains a mystery.
      Resistance to erythromycin in the respiratory pathogens Staphylococcus aureus and
      Streptococcus pneumoniae emerged rapidly and increased problematically. However,
      resistance is uncommon amongst the classic Bordetella species despite infections
      being treated with this macrolide for decades. Objectives: We examined whether
      the apparent progenitor of the classic Bordetella spp., Bordetella
      bronchiseptica, is able to rapidly generate de novo resistance to antibiotics
      and, if so, why such resistance might not persist and propagate. Methods:
      Independent strains of B. bronchiseptica resistant to erythromycin were generated
      in vitro by successively passaging them in increasing subinhibitory
      concentrations of this macrolide. Resistant mutants obtained were evaluated for
      their capacity to infect mice, and for other virulence properties including
      adherence, cytotoxicity and induction of cytokines. Results: B. bronchiseptica
      rapidly developed stable and persistent antibiotic resistance de novo. Unlike the
      previously reported trade-off in fitness, multiple independent resistant mutants
      were not defective in their rates of growth in vitro but were consistently
      defective in colonizing mice and lost a variety of virulence phenotypes. These
      changes rendered them avirulent but phenotypically similar to the previously
      described growth phase associated with the ability to survive in soil, water
      and/or other extra-mammalian environments. Conclusions: These observations raise
      the possibility that antibiotic resistance in some organisms results in trade
      offs that are not quantifiable in routine measures of general fitness such as
      growth in vitro, but are pronounced in various aspects of infection in the
      natural host.

PMID- 30107603
TI  - Evidence on the Association Between Cigarette Smoking and Incident Depression
      From the South African National Income Dynamics Study 2008-2015: Mental Health
      Implications for a Resource-Limited Setting.
AB  - Introduction: As a leading global disease risk factor, cigarette smoking has
      declined in some developed countries, but its health consequences are not well
      established in sub-Saharan Africa. This is particularly evident in South Africa,
      where few investigations have quantified the dually neglected challenges of
      cigarette smoking and depression, despite decades of research from developed
      countries. We investigated the association between cigarette smoking and incident
      depression, with the hypothesis that adolescents are particularly vulnerable.
      Methods: Panel data from the South African National Income Dynamics Study, a
      nationally representative sample of households at follow-up periods (years 2008
      2015), were used. Our incident cohort consists of 14 118 adult participants who
      were depression free at baseline. The generalized estimating equation models were
      fitted to assess the association between current cigarette smoking and incident
      depression. Results: Current cigarette smoking among individuals aged at least 15
      was significantly associated with incidents of depression among men (adjusted
      relative risk [aRR] = 1.16, 95% CI = 1.01 to 1.34), but not women. When the
      analyses were restricted to a sample population of older adolescents (ages 15
      19), current cigarettes smoking was significantly associated with incident
      depression in both men (aRR = 1.84, 95% CI = 1.18 to 2.88) and women (aRR = 2.47,
      95% CI = 1.15 to 5.29). Conclusion: The results suggest an important relationship
      between cigarette smoking and incident depression, particularly among older
      adolescents, who are developmentally vulnerable and socioeconomically
      disadvantaged to experiencing depression. There is a considerable need to
      implement and prioritize culturally and developmentally appropriate prevention
      and cessation measures to reduce cigarette smoking and depression directed at
      adolescent populations. Implications: There has been little population level
      research into the role of smoking on depression in sub-Saharan Africa, a region
      classified as a tobacco epidemic in the making. Our results have major
      implications for the often neglected crosscutting issues of tobacco control
      (Sustainable Development Goal 3.9) and mental health (Sustainable Development
      Goal 3.4). They indicate the role of smoking on depression, with the association
      being particularly pronounced among adolescent who are developmentally vulnerable
      and socioeconomically disadvantaged, and emphasize the need to implement and
      prioritize prevention and cessation measures directed at this population.

PMID- 30107602
TI  - Polymorphism of G4 associates: from stacks to wires via interlocks.
AB  - We examined the assembly of DNA G-quadruplexes (G4s) into higher-order structures
      using atomic force microscopy, optical and electrophoretic methods, NMR
      spectroscopy and molecular modeling. Our results suggest that parallel blunt
      ended G4s with single-nucleotide or modified loops may form different types of
      multimers, ranging from stacks of intramolecular structures and/or interlocked
      dimers and trimers to wires. Decreasing the annealing rate and increasing salt or
      oligonucleotide concentrations shifted the equilibrium from intramolecular G4s to
      higher-order structures. Control antiparallel and hybrid G4s demonstrated no
      polymorphism or aggregation in our experiments. The modification that mimics
      abasic sites (1',2'-dideoxyribose residues) in loops enhanced the
      oligomerization/multimerization of both the 2-tetrad and 3-tetrad G4 motifs. Our
      results shed light on the rules that govern G4 rearrangements. Gaining control
      over G4 folding enables the harnessing of the full potential of such structures
      for guided assembly of supramolecular DNA structures for nanotechnology.

PMID- 30107605
TI  - A Multi-Gene Analysis and Potential Spatial Distribution of Species of the
      Strodei Subgroup of the Genus Nyssorhynchus (Diptera: Culicidae).
AB  - Nyssorhynchus strodei (Root) is an understudied species of potential
      epidemiological importance, having been found naturally infected in Brazil with
      Plasmodium falciparum Welch, Plasmodium vivax Grassi & Feletti, and Plasmodium
      malariae Feletti & Grassi. It belongs to the strodei subgroup that includes
      Nyssorhynchus albertoi (Unti), Nyssorhynchus arthuri (Unti), Nyssorhynchus
      rondoni (Neiva & Pinto), Nyssorhynchus striatus (Sant'Ana & Sallum), and three
      unnamed species, Nyssorhynchus arthuri B, Nyssorhynchus arthuri C, and
      Nyssorhynchus arthuri D. As the accurate identification of vector species is of
      fundamental importance for public health entomology, the aim of the study was to
      provide additional information for the presence of seven species that had been
      previously misidentified as Ny. strodei. Bayesian phylogenetic analyses using DNA
      sequences of the genes COI mtDNA, white, CAD and CAT nuclear genes confirmed Ny.
      albertoi, Ny. arthuri, Ny. strodei, and Ny. striatus as distinct groups within
      the strodei subgroup and corroborated the presence of three undescribed species
      under the name Ny. arthuri. Results of the GMYC model analysis corroborated Ny.
      arthuri B, Ny. arthuri C, and Ny. arthuri D; however, they did not distinguish
      between Ny. strodei and Ny. albertoi. Predicted distribution of seven species
      based on maximum entropy in MaxEnt showed that each species has its specific
      ecological niche suitability.

PMID- 30107606
TI  - Incorporating diffusion- and perfusion-weighted MRI into a radiomics model
      improves diagnostic performance for pseudoprogression in glioblastoma patients.
AB  - Background: Pseudoprogression is a diagnostic challenge in early post-treatment
      glioblastoma. We therefore developed and validated a radiomics model using
      multiparametric MRI to differentiate pseudoprogression from early tumor
      progression in patients with glioblastoma. Methods: The model was developed from
      the enlarging contrast-enhancing portions of 61 glioblastomas within 3 months
      after standard treatment with 6472 radiomic features being obtained from contrast
      enhanced T1-weighted imaging, fluid-attenuated inversion recovery imaging, and
      apparent diffusion coefficient (ADC), and cerebral blood volume (CBV) maps.
      Imaging features were selected using a least absolute shrinkage and selection
      operator (LASSO) logistic regression model with 10-fold cross-validation.
      Diagnostic performance for pseudoprogression was compared with that for single
      parameters (mean and minimum ADC and mean and maximum CBV) and single imaging
      radiomics models using the area under the receiver-operating-characteristics
      curve (AUC). The model was validated with an external cohort (n = 34) imaged on a
      different scanner and an internal prospective registry data (n = 23). Results:
      Twelve significant radiomic features (3 from conventional, 2 from diffusion and 7
      from perfusion MRI) were selected for model construction. The multiparametric
      radiomics model (AUC 0.90) showed significantly better performance than any
      single ADC or CBV parameter (AUC 0.57-0.79, P<.05), and better than single
      radiomics model using conventional MRI (AUC 0.76, P =.012), ADC (AUC 0.78, P
      =.014), or CBV (AUC 0.80, P=.43). The multiparametric radiomics showed higher
      performance in the external validation (AUC 0.85) and internal validation (AUC
      0.96) than any single approach, thus demonstrating robustness. Conclusions:
      Incorporating diffusion- and perfusion-weighted MRI into a radiomics model
      improved diagnostic performance for identifying pseudoprogression and showed
      robustness in a multicenter setting.

PMID- 30107608
TI  - Type 1 autoimmune pancreatitis: a capsule-like rim surrounding the enlarged
      pancreas.

PMID- 30107604
TI  - Immunohistochemical Method and Histopathology Judging for the Systemic Synuclein
      Sampling Study (S4).
AB  - Immunohistochemical (IHC) alpha-synuclein (Asyn) pathology in peripheral biopsies
      may be a biomarker of Parkinson disease (PD). The multi-center Systemic Synuclein
      Sampling Study (S4) is evaluating IHC Asyn pathology within skin, colon and
      submandibular gland biopsies from 60 PD and 20 control subjects. Asyn pathology
      is being evaluated by a blinded panel of specially trained neuropathologists.
      Preliminary work assessed 2 candidate immunoperoxidase methods using a set of PD
      and control autopsy-derived sections from formalin-fixed, paraffin-embedded
      blocks of the 3 tissues. Both methods had 100% specificity; one, utilizing the
      5C12 monoclonal antibody, was more sensitive in skin (67% vs 33%), and was chosen
      for further use in S4. Four trainee neuropathologists were trained to perform S4
      histopathology readings; in subsequent testing, their scoring was compared to
      that of the trainer neuropathologist on both glass slides and digital images.
      Specificity and sensitivity were both close to 100% with all readers in all
      tissue types on both glass slides and digital images except for skin, where
      sensitivity averaged 75% with digital images and 83.5% with glass slides.
      Semiquantitative (0-3) density score agreement between trainees and trainer
      averaged 67% for glass slides and 62% for digital images.

PMID- 30107607
TI  - BZR1 Transcription Factor Regulates Heat Stress Tolerance Through FERONIA
      Receptor-Like Kinase-Mediated Reactive Oxygen Species Signaling in Tomato.
AB  - BRASSINAZOLE RESISTANT 1 (BZR1), the critical regulator of brassinosteroid (BR)
      response, participates in various BR-mediated developmental processes. However,
      the roles of BZR1 in stress tolerance are less clear. Here, we found that BZR1
      like protein in tomato controls BR response and is involved in thermotolerance by
      regulating the FERONIA (FER) homologs. The CRISPR-bzr1 mutant showed reduced
      growth and was not responsive to 24-epibrassinolide (EBR) with regard to the
      promotion of plant growth. Mutation in BZR1 impaired the induction of RESPIRATORY
      BURST OXIDASE HOMOLOG1 (RBOH1), production of H2O2 in the apoplast and heat
      tolerance. Exogenous H2O2 recovered the heat tolerance of the tomato bzr1 mutant.
      Overexpression of BZR1 enhanced the production of apoplastic H2O2 and heat stress
      responses. However, silencing of RBOH1 abolished the BZR1-mediated heat
      tolerance. Further analysis showed that BZR1 bound to the promoters of FERONIA2
      (FER2) and FER3 and induced their expression. Silencing of FER2/3 suppressed BZR1
      dependent BR signaling for the induction of RBOH1 transcripts, accumulation of
      apoplastic H2O2 and heat tolerance. These results indicate that BZR1 regulates
      heat stress responses in tomato through RBOH1-dependent reactive oxygen species
      (ROS) signaling, which is at least partially mediated by FER2 and FER3.

PMID- 30107609
TI  - Effects of genotype and sex on technological properties and fatty acid
      composition of duck meat.
AB  - Study was conducted to determine the effects of genotype and sex on the
      technological properties and fatty acid composition of duck meat. Native (n = 15)
      and Peking (n = 15) ducks were slaughtered at 10 wk old, and meat samples were
      taken from M. pectoralis major (breast) and M. peroneus longus (thigh). The pH24,
      drip loss, expressed juice, cooking loss, Warner-Bratzler shear force (WBSF),
      color variables, fatty acid composition, and sensory characteristics were
      examined. Ultimate pH of breast meat in Peking ducks (6.01) was higher than that
      of native ducks (5.82). The breast drip loss (3.40%) and cooking loss (31.23%) in
      native ducks were higher than those in Peking ducks (2.77 and 26.69%,
      respectively). The expressed juice of thigh meat in native ducks (8.23%) was
      higher than that of Peking ducks (6.52%). Genotype and sex had no significant
      influence on WBSF and meat color. Lightness (L*) values of breast and thigh skin
      were higher in Peking ducks than native ones. In panel evaluation, panelists
      evaluated the meat of Peking ducks with higher odor and flavor intensity. Breast
      meat of native ducks had higher Sigma-polyunsaturated fatty acid (?PUFA), ?n-6
      (omega-6) proportions, nutritive value, the ratio of SigmaPUFA to Sigma-saturated
      fatty acid (?SFA) and lower ?SFA, atherogenic and thrombogenic indices than
      Peking ducks. Instrumental and sensory characteristics of duck meat as well as
      fatty acid composition indicate that duck finishing can be considered as an
      alternative source of high-quality meat production.

PMID- 30107610
TI  - Neutrophil Count Is Associated With Reduced Gray Matter and Enlarged Ventricles
      in First-Episode Psychosis.
AB  - Although there is recent evidence that cells from the peripheral immune system
      can gain access to the central nervous system in certain conditions such as
      multiple sclerosis, their role has not been assessed in psychosis. Here, we aimed
      to explore whether blood cell count was associated with brain volume and/or
      clinical symptomatology. A total of 218 participants (137 first-episode psychosis
      patients [FEP] and 81 healthy controls [HC]) were included in the study. For each
      participant, a T1 structural image was acquired, from which brain tissue volumes
      were calculated. We found that, in FEP, neutrophil count was associated with
      reduced gray matter (GM) volume (beta = -0.117, P < .001) and increased
      cerebrospinal fluid volume (beta = 0.191, P = .007). No associations were
      observed in HC. GM reduction was generalized but more prominent in certain
      regions, notably the thalamus, the anterior insula, and the left Heschl's gyrus,
      among many others. Neutrophil count was also associated with the total PANSS
      score (beta = 0.173, P = .038), including those items assessing hallucinations
      (beta = 0.182, P = .028) and avolition (beta = 0.197, P = .018). Several
      confounders, such as antipsychotic medication, body mass index, and smoking, were
      controlled for. Overall, the present study may represent the first indirect
      evidence of brain tissue loss associated with neutrophils in psychosis, and lends
      support to the hypothesis of a dysregulated immune system. Higher neutrophil
      count was also associated with more severe clinical symptomatology, which renders
      it a promising indicator of schizophrenia severity and could even give rise to
      new therapies.

PMID- 30107611
TI  - Water-soluble substances of wheat: a potential preventer of aflatoxin B1-induced
      liver damage in broilers.
AB  - Aflatoxin B1 (AFB1) is very harmful for broiler production and public health. The
      water-soluble castoff in gluten production, i.e., the water-soluble substances of
      wheat (WSW) that contains 14% pentosan has positive effect on animal nutrient
      absorption, immunity, and antioxidation. Our study aims to investigate the
      preventive effects of WSW against AFB1-induced broiler liver injury. One day-old
      Arbor Acres broilers were randomly separated to 4 groups and were, respectively,
      fed with control diet, diet with 5 mg/kg AFB1 standard, diet with 5 mg/kg AFB1
      standard and 214 ml/kg WSW, and diet with 214 ml/kg WSW continuously for 28 d.
      The histopathological, ultra-structural, and serological changes were tested to
      evaluate liver damage. The hallmarks of hepatocellular autophagy, apoptosis, and
      inflammation were measured by Western Blot and real-time polymerase chain
      reaction. The content of AFB1 in chicken liver was detected with an ultra-high
      performance liquid chromatography linked with the fluorescence detection method.
      The results showed that (i) WSW restored AFB1-induced changes in serum
      biochemical parameters, and ameliorated histomorphological changes in
      hepatocytes, (ii) WSW reduced the content of AFB1 in chicken liver, (iii) WSW
      alleviated AFB1-induced autophagy inhibition by up-regulating hepatic LC3, beclin
      1, and down-regulating hepatic mTOR and cytoplasmic P53 expressions, (iv) WSW
      alleviated AFB1-induced hepatocellular apoptosis via inhibiting pro-apoptotic
      gene expression (nuclear P53, Caspase3, Bax), and promoting anti-apoptotic gene
      expression (bcl-2), (v) WSW feeding ameliorated AFB1-induced liver inflammation
      via impeding TLR4/NF- kappaB and IL-1/NF- kappaB signaling pathways, down
      regulating pro-inflammatory cytokines (IL-1 beta, IL-6, and IL-8), and markedly
      up-regulating anti-inflammatory genes (IL-10 and HO-1). Conclusively, WSW is a
      potential preventer of AFB1-induced broiler liver damage by reducing the AFB1
      content in liver, accelerating hepatocellular autophagy and inhibiting
      hepatocytes apoptosis and liver inflammation.

PMID- 30107612
TI  - Vascular access placement and mortality in elderly incident hemodialysis
      patients.
AB  - Background: Arteriovenous fistulas (AVFs) are the preferred vascular access type
      in most hemodialysis patients. However, the optimal vascular access type in
      octogenarians and older (>=80 years) hemodialysis patients remains widely debated
      given their limited life expectancy and lower AVF maturation rates. Methods:
      Among incident hemodialysis patients receiving care in a large national dialysis
      organization during 2007-2011, we examined patterns of vascular access type
      conversion in 1 year following dialysis initiation in patients <80 versus >=80
      years of age. Among a subcohort of patients >=80 years of age, we examined the
      association between vascular access type conversion and mortality using
      multivariable survival models. Results: In the overall cohort of 100 804
      patients, the prevalence of AVF/arteriovenous graft (AVG) as the primary vascular
      access type increased during the first year of hemodialysis, but plateaued
      thereafter. Among 8356 patients >=80 years of age and treated for >1 year, those
      with initial AVF/AVG use and placement of AVF from a central venous catheter
      (CVC) had lower mortality compared with patients with persistent CVC use. When
      the reference group was changed to patients who had AVF placement from a CVC in
      the first year of dialysis, those with initial AVF use had similar mortality. A
      longer duration of CVC use was associated with incrementally worse survival.
      Conclusions: Among incident hemodialysis patients >=80 years of age, placement of
      an AVF from a CVC within the first year of dialysis had similar mortality
      compared with initial AVF use. Our data suggest that initial CVC use with later
      placement of an AVF may be an acceptable option among elderly hemodialysis
      patients.

PMID- 30107614
TI  - The high conserved cellular receptors of avian leukosis virus subgroup J in
      Chinese local chickens contributes to its wide host range.
AB  - Avian leukosis virus (ALV) is a tumor-inducing virus that spreads among most
      chicken species, causing serious financial losses for the poultry industry.
      Subgroup J avian leukosis virus (ALV-J) is a recombinant exogenous ALV, which
      shows more extensive host range in comparison with other subgroups, especially in
      Chinese local chickens. To identify the relationship between ALV-J host range and
      the polymorphism of its cellular receptors, we performed a wide range
      epidemiological investigation of current ALV-J infection in Chinese local
      chickens, and discovered that all the 18 local chicken breeds being investigated
      from main local chicken breeding provinces were ALV-J positive. Furthermore, we
      cloned ALV-J cellular receptor genes of chNHE1 and chANXA2 of these 18 chicken
      breeds. Sequence alignment demonstrated that despite several regular mutations at
      the nucleotide level, there were no corresponding amino acid mutations for either
      chNHE1 gene or chANXA2 gene. Additionally, virus entry assay indicated that the
      level of viral enter into cells is stable among different chicken breeds. Results
      of this study indicated that the wide host range of ALV-J in Chinese local
      chickens was partially due to the high conservatism of its cellular receptors,
      and also provide target sites for drug design of resistance to ALV-J infection.

PMID- 30107615
TI  - A review of environmental enrichment for laying hens during rearing in relation
      to their behavioral and physiological development.
AB  - Globally, laying hen production systems are a focus of concern for animal
      welfare. Recently, the impacts of rearing environments have attracted attention,
      particularly with the trend toward more complex production systems including
      aviaries, furnished cages, barn, and free-range. Enriching the rearing
      environments with physical, sensory, and stimulatory additions can optimize the
      bird's development but commercial-scale research is limited. In this review,
      "enrichment" is defined as anything additional added to the bird's environment
      including structurally complex rearing systems. The impacts of enrichments on
      visual development, neurobehavioral development, auditory stimulation, skeletal
      development, immune function, behavioral development of fear and pecking, and
      specifically pullets destined for free-range systems are summarized and areas for
      future research identified. Visual enrichment and auditory stimulation may
      enhance neural development but specific mechanisms of impact and suitable
      commercial enrichments still need elucidating. Enrichments that target left/right
      brain hemispheres/behavioral traits may prepare birds for specific types of adult
      housing environments (caged, indoor, outdoor). Similarly, structural enrichments
      are needed to optimize skeletal development depending on the adult layer system,
      but specific physiological processes resulting from different types of exercise
      are poorly understood. Stimulating appropriate pecking behavior from hatch is
      critical but producers will need to adapt to different flock preferences to
      provide enrichments that are utilized by each rearing group. Enrichments have
      potential to enhance immune function through the application of mild stressors
      that promote adaptability, and this same principle applies to free-range pullets
      destined for variable outdoor environments. Complex rearing systems may have
      multiple benefits, including reducing fear, that improve the transition to the
      layer facility. Overall, there is a need to commercially validate positive
      impacts of cost-effective enrichments on bird behavior and physiology.

PMID- 30107613
TI  - Deep genome annotation of the opportunistic human pathogen Streptococcus
      pneumoniae D39.
AB  - A precise understanding of the genomic organization into transcriptional units
      and their regulation is essential for our comprehension of opportunistic human
      pathogens and how they cause disease. Using single-molecule real-time (PacBio)
      sequencing we unambiguously determined the genome sequence of Streptococcus
      pneumoniae strain D39 and revealed several inversions previously undetected by
      short-read sequencing. Significantly, a chromosomal inversion results in
      antigenic variation of PhtD, an important surface-exposed virulence factor. We
      generated a new genome annotation using automated tools, followed by manual
      curation, reflecting the current knowledge in the field. By combining sequence
      driven terminator prediction, deep paired-end transcriptome sequencing and
      enrichment of primary transcripts by Cappable-Seq, we mapped 1015 transcriptional
      start sites and 748 termination sites. We show that the pneumococcal
      transcriptional landscape is complex and includes many secondary, antisense and
      internal promoters. Using this new genomic map, we identified several new small
      RNAs (sRNAs), RNA switches (including sixteen previously misidentified as sRNAs),
      and antisense RNAs. In total, we annotated 89 new protein-encoding genes, 34
      sRNAs and 165 pseudogenes, bringing the S. pneumoniae D39 repertoire to 2146
      genetic elements. We report operon structures and observed that 9% of operons are
      leaderless. The genome data are accessible in an online resource called
      PneumoBrowse (https://veeninglab.com/pneumobrowse) providing one of the most
      complete inventories of a bacterial genome to date. PneumoBrowse will accelerate
      pneumococcal research and the development of new prevention and treatment
      strategies.

PMID- 30107616
TI  - Classification of dengue cases in Southwest India based on the WHO systems-a
      retrospective analysis.
AB  - Background: The WHO dengue classification 1997 was revised in 2009 and the
      revised classification system has now been in use for the past decade. This study
      was carried out to compare the 1997 and revised classifications in assessing the
      severity of dengue infection among all age groups during a dengue outbreak in
      southwest India. Methodology: This retrospective cross-sectional study was
      carried out including serologically confirmed dengue cases. A total of 1033
      dengue cases were classified on the basis of the 1997 WHO classification and 2009
      revised classification. The statistical analysis was carried out using SPSS 15.0
      for Windows (SPSSTM Inc, Chicago, IL, USA). Results: Both the 1997 and revised
      WHO classifications were applied to 1033 confirmed dengue cases, including 692
      males (67%) and 341 females (33%). The median age of the study participants was
      23 years (IQR 10-33), including 112 (10.8%) children at and below the age of 5
      years. The level of agreement between the two systems of classification was poor
      (kappa=0.143, 0.055-0.198, p-value <0.001). Conclusion: A greater sensitivity and
      specificity of the revised classification was observed in comparison with the
      1997 WHO classification. In the context of changing dengue epidemiology and
      geographical expansion, the revised classification is helpful in the
      identification of severe cases, facilitating timely management.

PMID- 30107617
TI  - Sleep fragmentation delays wound healing in a mouse model of type 2 diabetes.
AB  - Study Objectives: This study tested the hypothesis that sleep fragmentation (SF)
      delays wound healing in obese B6.BKS(D)-Leprdb/J (db/db) mice with impaired
      leptin signaling and type 2 diabetes compared with wild-type C57BL/6J (B6) mice.
      Methods: Adult male mice (n = 34) were anesthetized and bilateral full-thickness
      excisional wounds were created on the back of each mouse. Half of the db/db and
      B6 mice were housed in SF cages equipped with a bar that moved across the cage
      floor every 2 min, 12 hr/day for 23 days. The other half of each group of mice
      was housed in the same room and did not experience SF. The dependent measures
      were number of days required to achieve wound closure, mRNA expression of four
      inflammatory mediators, blood glucose, insulin, and corticosterone. Results: SF
      in the db/db mice caused a significant delay in wound healing relative to db/db
      mice with no SF. Days to achieve 50 per cent wound healing were 13.3 +/- 0.4 with
      SF compared with 10.3 +/- 0.7 without SF. All B6 mice achieved 50 per cent wound
      healing within 6 days and complete healing after 16 days. SF caused a significant
      increase in wound levels of TNF-alpha mRNA only in the db/db mice and an increase
      in corticosterone only in the B6 mice. Conclusions: The delayed wound healing in
      obese, diabetic mice caused by SF is homologous to delayed wound healing in some
      patients with type 2 diabetes. The results support the interpretation that
      altered leptinergic signaling and inflammatory proteins contribute to delayed
      wound healing.

PMID- 30107618
TI  - [Austrian benchmarking project for ERCP: a 10-year report].
AB  - The quality assurance program "Benchmarking ERCP", that his been under the
      patronage of the OGGH for ten years (with a one-year break in 2008), in
      collaboration with the Institute for Applied Statistics University Linz, has
      followed patient safety measures and successes while undergoing ERCP in Austria.
      A total of 28 319 examinations were registered. The participating centers all had
      different ERCP frequency and variable expertise, thereby enabling them to
      recognise individual problems in terms of success, cannulation and complication
      rates (3.9 % post-ERCP pancreatitis, 3.8 % bleeding, 0.6 % perforation, 1.2 %
      cholangitis, 1.0 % cardiopulmonary complications). The aim of quality assurance
      measures in medicine is to ensure the best possible patient care.

PMID- 30107619
TI  - Gut Microbiome in BALB/c and C57BL/6J Mice Undergoing Experimental Thyroid
      Autoimmunity Associate with Differences in Immunological Responses and Thyroid
      Function.
AB  - Experimental models of hyperthyroid Graves' disease (GD) and Graves' orbitopathy
      (GO) are efficiently developed by genetic immunisation by electroporation with
      human thyrotropin hormone receptor (hTSHR) A-subunit plasmid in female BALB/c (H
      2d) mice. We investigated susceptibility in C57BL/6 J (H-2b) animals to allow
      studies on disease mechanisms in transgenic and immune response gene knock-out
      mice. Higher numbers of female C57BL/6 J were positive for pathogenic thyroid
      stimulating antibodies, but induced hyperthyroidism remained at a low frequency
      compared to BALB/c animals. Assessment of hTSHR specific T cells showed reduced
      proliferation in C57BL/6 J animals accompanied with anti-inflammatory IL-10, with
      less pro-inflammatory IFN-gamma compared to BALB/c. Whilst the orbital tissue
      from immune BALB/c mice showed inflammation and adipogenesis, in contrast C57BL/6
      J animals showed normal pathology. We characterised the gut microbiota using 16 S
      ribosomal RNA gene sequencing to explore its possible pathogenic role in the
      model. Despite being housed under identical conditions, we observed significantly
      different organisation of the microbiota (beta-diversity) in the two strains.
      Taxonomic differences were also noted, with C57BL/6 J showing an enrichment of
      Operational Taxonomic Units (OTUs) belonging to the Paludibacter and Allobaculum,
      followed by Limibacter, Anaerophaga and Ureaplasma genera. A higher number of
      genera significantly correlating with clinical features was observed in C57BL/6 J
      compared to BALB/c; for example, Limibacter OTUs correlated negatively with
      thyroid-stimulating antibodies in C57BL/6 J mice. Thus, our data suggest gut
      microbiota may play a pivotal immunomodulatory role that differentiates the
      thyroid function and orbital pathology outcome in these two inbred strains
      undergoing experimental GO.

PMID- 30107620
TI  - [Duodenale levodopa and apomorphine infusion for motor complications in advanced
      Parkinson's disease].
AB  - Development of motor fluctuations and dyskinesia characterizes the transition
      from the early to the advanced Parkinson stage. Current oral therapeutic
      strategies aim at increasing the number of levodopa administrations and extending
      its benefit by the association of enzyme blockers (MAO- and COMT-inhibitors) and
      dopamine agonists. However, as disease progresses, mobility becomes progressively
      dependent on levodopa absorption and plasma bioavailability, resulting in
      disabling motor complications. If patients continue to experience off time with
      functional impact on activities of daily living after best oral medication
      adjustments, implementation of infusion therapies with apomorphine or levodopa,
      and surgical techniques should be considered. Compared with pulsatile oral
      therapy implementation of apomorphine and levodopa infusion determines more
      continuous striatal dopamine receptors stimulation resulting in significant
      reduction of off-time and dyskinesia, particularly peak-dose. However, long-term
      experience with these treatments shows that motor complications are not abolished
      by continuous receptor stimulation suggesting that synaptic plasticity and
      connectivity changes are not easily reversed once they are established. Early
      intervention ideally would target patients as soon as motor complications begin
      rather than at late stage. Preliminary evidence from early deep brain stimulation
      or early pump treatment suggests that this is feasible but before it is
      implemented in clinical practice it would require a detailed cost-benefit
      analysis.

PMID- 30107621
TI  - The Use of a Game-Based Decision Aid to Educate Pregnant Women about Prenatal
      Screening: A Randomized Controlled Study.
AB  - PURPOSE:  This project developed and evaluated the efficacy of a game decision
      aid among pregnant women about prenatal screening in a randomized controlled
      study. METHOD:  Participants were recruited from an obstetric clinic of an
      academic urban medical center and randomized (n = 73) to one of two study groups:
      the control group (n = 39) that used a brochure or the intervention group (n =
      34) that also used a game decision aid. RESULT:  Participants who played the game
      had higher knowledge scores (m = 21.41, standard deviation [SD] = 1.74) than
      participants in the control group (m = 19.59; SD = 3.31), p = 0.004. The median
      time of game playing was 6:43 minutes (range: 2:17-16:44). The groups were
      similar in frequency of completing screening after the study, control = 6 (15%)
      versus intervention = 11 (32%), p = 0.087. However, the more interaction with the
      game resulted in more positive attitudes toward screening. CONCLUSION:  The
      addition of a game decision aid was effective in educating pregnant women about
      prenatal screening. As other genetic testing decisions continue to increase
      within clinical care, game-based decision tools may be a constructive method of
      informed decision-making.

PMID- 30107622
TI  - The Relation Between Epicardial Fat Tissue Thickness and TSH Receptor Antibody in
      Hyperthyroidism.
AB  - BACKGROUND: Although hyperthyroidism may be associated with atherosclerosis, its
      pathogenesis is not well known. TSH receptor antibody (TRAb) has been shown to be
      responsible for increased orbital fat tissue in Graves ophthalmopathy. Epicardial
      fat tissue thickness (EFT) has been found to be increased in case of overt
      hyperthyroidism. In our study, we aimed to investigate if TRAb is associated with
      the increased EFT in newly diagnosed hyperthyroidism. METHODS: Twenty six TRAb
      positive (group 1) and 26 TRAb negative (group 2) newly diagnosed patients with
      hyperthyroidism, and 26 healthy control subjects (group 3) were enrolled. EFT was
      measured by the same cardiologist using an echocardiography device. Serum TRAb
      levels were measured by the radio-receptor assay and levels above 1.75 IU/L were
      considered as positive. RESULTS: There was no difference among groups in terms of
      age, gender and body mass index. Although there was no significant difference
      between group 1 and 2, both group 1 (0.38+/-0.15 cm) and group 2 (0.4+/-0.17 cm)
      had significantly higher EFT levels when compared to group 3 (0.25+/-0.06 cm)
      (p=0.004 and p=0.001, respectively). However we did not find any correlation
      between TRAb and EFT levels. CONCLUSION: The results of our study suggested that
      EFT was increased in hyperthyroidism and this increasing was not dependent of
      TRAb level. EFT elevation might be depending directly to the cardiovascular
      effects of hyperthyroidism.

PMID- 30107623
TI  - Acute Administration of Tibolone Prevents Oxidative Stress in Ovariectomized Rats
      Fed High-Fat-and-Fructose Diet.
AB  - In addition to oxidative stress due to the increase of free radicals, estrogen
      deficiency is associated with changes in enzymatic activity, glutathione redox
      ratio (GSH/GSSG), and the content of oxidative markers such as malondialdehyde.
      Tibolone, a synthetic steroid, has been used as an elective treatment for the
      relief of menopausal symptoms. However, the acute effects of hormonal therapy
      with tibolone on metabolic parameters and oxidative stress markers associated
      with the first stages of estrogen deficiency are still unknown. The study aimed
      to evaluate if the acute administration of tibolone reduces oxidative stress in
      ovariectomized rats fed high-fat-and-fructose diet. Rats were fed a standard diet
      or a diet consisting of 10% lard-supplemented chow and 20% high-fructose syrup in
      the drinking water plus tibolone or vehicle for seven days. Weight, cholesterol,
      triglycerides, and glucose levels, as well as antioxidant enzymes and oxidative
      stress markers were quantified in the serum of each experimental group. It was
      observed that seven days of diet and tibolone treatment in the ovariectomized
      group reduced weight, triglycerides, cholesterol, glucose levels and advanced
      glycation end products but did not change GSH/GSSG ratio nor the enzymatic
      activity of superoxide dismutase. Also, both glutathione peroxidase and
      glutathione reductase activity decreased, as well as malondialdehyde levels.
      These results suggest that the acute treatment with tibolone prevented the
      changes in the metabolic parameters analyzed as well as the increase in the
      levels of malondialdehyde and AGEs induced by ovariectomy and high-fat diet.

PMID- 30107624
TI  - The Abdominal Aortic Intima-Media Thickness Increases in Patients with Primary
      Hyperparathyroidism.
AB  - BACKGROUND: We aimed to determine whether there is an increase in aortic intima
      media thickness values measured from the abdominal aorta in addition to the
      traditional carotid intima-media thickness in patients with primary
      hyperparathyroidism and to determine the parameters closely related to aortic
      intima-media thickness. METHODS: This perspective study included 65 primary
      hyperparathyroidism patients and 30 healthy-controls. Routine laboratory tests
      for the diagnosis of hyperparathyroidism and vascular ultrasound examinations
      were performed. Common carotid, internal carotid, and abdominal aortic intima
      media thickness were measured. The participants of the study was divided into 3
      groups as the control (Group-I), the medical treatment (Group-II) due to primary
      hyperparathyroidism, and the planned surgery (group-III). RESULTS: Aortic intima
      media thickness, serum urea, creatinine, glucose, uric acid, hs-CRP, parathyroid
      hormone, calcium and urine calcium levels increased significantly from Group-I to
      Group-III and T-scores and serum phosphorus in levels decreased significantly.
      Carotid intima-media thicknesses were not significantly different between the
      groups. Serum and urinary calcium levels were independently associated with
      aortic intima-media thickness. Aortic intima-media thickness, serum phosphorus,
      parathyroid hormone, T-scores, serum and urinary calcium levels are independent
      indicators for Group-III. When the cut-off value of aortic intima-media thickness
      was taken as 1.5 mm, 80.6% sensitivity and 89.1% specificity were determined for
      patients who would go to surgery. CONCLUSION: Serum and urine calcium levels were
      independently associated with aortic intima-media thickness. Aortic intima-media
      thickness is more useful than carotid intima-media thickness in showing vascular
      organ involvement in patients with primary hyperparathyroidism.

PMID- 30107625
TI  - Perioperative Management of Endocrine Active Adrenal Tumors.
AB  - Endocrine active adrenal tumors are associated with a relevant risk of
      complications during surgery, either due to direct hemodynamic effects of the
      hormone excess or due to hormone related comorbidities. Over the last decades,
      careful preoperative evaluation and improved peri-interventional medical
      management of affected patients has resulted in a significant reduction of
      perioperative complications. In addition, improvement in anesthesia and surgical
      techniques with the feasibility of laparoscopic adrenalectomy have contributed to
      reduce morbidity. Nevertheless, there are still several challenges to be
      considered in the perioperative care of these patients. Due to the rarity of
      functionally active adrenal tumors, there are no prospective data available to
      guide clinical management. Accordingly, most recommendations are based on
      retrospective data analysis, expert opinion or carry weak evidence based on small
      series or case reports. The aim of this review is to summarize the current
      knowledge and to suggest practical approaches to reduce perioperative
      complications in endocrine active adrenal tumors. This review exclusively deals
      with data from adult patients with functionally active adrenal tumors.

PMID- 30107626
TI  - Treatment of low grade dysplasia in Barrett's esophagus with a new-generation
      cryoballoon device.

PMID- 30107627
TI  - Revision of migrated self-expandable metal stent by the remOVE device.

PMID- 30107628
TI  - Elective cholecystectomy after reversal of septic shock using multimodality
      endoscopic gallbladder drainage.

PMID- 30107629
TI  - An unsuspicious duodenal foreign body.

PMID- 30107630
TI  - Dislodged hood stuck in submucosal tunnel: retrieval during peroral endoscopic
      myotomy.

PMID- 30107631
TI  - Novel simultaneous endoscopic ultrasound-guided hepaticoduodenostomy and
      hepaticogastrostomy for recurrent hepatic hilar obstruction.

PMID- 30107632
TI  - The spectrum of confocal endomicroscopy findings in a cystic neuroendocrine tumor
      of the pancreas.

PMID- 30107633
TI  - Endoscopically guided percutaneous suturing to facilitate closure of a large
      gastrocutaneous fistula with an over-the-scope clip.

PMID- 30107634
TI  - Endoscopic dual therapy for giant peptic ulcer hemorrhage.

PMID- 30107635
TI  - Oxygen isotopes in tree rings are less sensitive to changes in tree size and
      relative canopy position than carbon isotopes.
AB  - Stable isotope ratios in tree rings have become an important proxy for
      palaeoclimatology, particularly in temperate regions. Yet temperate forests are
      often characterized by heterogeneous stand structures, and the effects of stand
      dynamics on carbon (delta13 C) and oxygen isotope ratios (delta18 O) in tree
      rings are not well explored. In this study, we investigated long-term trends and
      offsets in delta18 O and delta13 C of Picea abies and Fagus sylvatica in relation
      to tree age, size, and distance to the upper canopy at seven temperate sites
      across Europe. We observed strong positive trends in delta13 C that are best
      explained by the reconstructed dynamics of individual trees below the upper
      canopy, highlighting the influence of light attenuation on delta13 C in shade
      tolerant species. We also detected positive trends in delta18 O with increasing
      tree size. However, the observed slopes are less steep and consistent between
      trees of different ages and thus can be more easily addressed. We recommend
      restricting the use of delta13 C to years when trees are in a dominant canopy
      position to infer long-term climate signals in delta13 C when relying on material
      from shade-tolerant species, such as beech and spruce. For such species, delta18
      O should be in principle the superior proxy for climate reconstructions.

PMID- 30107636
TI  - Anhedonia and suicidal thoughts and behaviors in psychiatric outpatients: The
      role of acuity.
AB  - BACKGROUND: Anhedonia-impairment related to the experience of pleasure-has been
      identified as a potential risk factor for suicide, with some mixed findings. The
      current study sought to clarify the role of acuity of anhedonia in the
      relationship between anhedonia and suicidal thoughts and behaviors by comparing
      acutely and chronically anhedonic subjects on severity of suicidal ideation (SI)
      and suicide attempt (SA) history. METHODS: Psychiatric outpatients (N = 395) were
      administered the Columbia Suicide Severity Rating Scale, the Beck Scale for
      Suicidal Ideation and a modified version of the Snaith-Hamilton Pleasure Scale
      (SHPS); SI measures were readministered at a 1-month follow-up (N = 289, 73%).
      Participants were classified as acutely anhedonic, chronically anhedonic and
      nonanhedonic based on their responses to the SHPS at initial assessment. RESULTS:
      Controlling for symptoms of anxiety and depression, acute anhedonia was cross
      sectionally and prospectively associated with greater severity of SI compared to
      the nonanhedonic group; no differences in severity of SI were found between the
      chronically anhedonic and nonanhedonic group at either time point. Anhedonia
      grouping was not associated with SA history. CONCLUSION: Changes in capacity to
      experience pleasure may be more informative of near-term SI than typically low
      pleasure levels. Future investigation should focus on the relationship between
      acute anhedonia and imminent suicidal behavior.

PMID- 30107637
TI  - Assessment of the results of a three-year program for National Standardization
      and Quality Improvement of Medical Laboratories on Drug of Abuse Testing by the
      Ministry of Health in Turkey.
AB  - The aim of this study is to assess the results of inspections in the last three
      years of drug abuse testing in medical laboratories according to the latest
      regulations in Turkey. The on-site inspections of medical laboratories for drugs
      abuse testing performed in Alcohol and Drug Addiction Treatment Centers during
      2014-2016 are described, and laboratory processes and performance evaluated. The
      performance of 35 laboratories in 2014, 62 laboratories in 2015, and 94
      laboratories in 2016 were scored as the sum of the scores for all answers on the
      inspection form. An inspected laboratory was considered to have an unconformity
      if the total score was less than 2/3 of maximum score. The total scores of
      inspections and the number of laboratories with between years were compared using
      one-way analysis of variance and slope Chi-square for trend test, respectively.
      Total scores increased statistically significantly from 35.9 +/- 16.2 in 2014, to
      43.5 +/- 16.3 in 2015 and 49.1 +/- 1.3 in 2016 (p < 0.001). The laboratories with
      unconformities decreased statistically significantly from 57% in 2014 to 37% in
      2015 and 22% in 2016 (p < 0.001). The published legislation and the inspections
      contributed to national standardization and improved quality of service in
      medical laboratories for drug abuse testing.

PMID- 30107638
TI  - An Anthropological Examination of the Types of Skeletal Fractures Resulting from
      Fatal High (?3 m) Free Falls.
AB  - Fatal falls from heights (?3 m) often result in blunt force trauma (BFT) to the
      skeleton. The fracture patterns that result from this BFT mechanism are well
      understood in forensic anthropology and forensic pathology; however, details of
      the specific types of fractures that result remain poorly documented. The aim of
      this study was to provide a detailed examination of the types of fractures that
      may result from fatal high falls. Fractures were recorded from 95 full-body
      postmortem computed tomography scans of individuals known to have died from a
      high fall. Trauma was then analyzed taking into account the extrinsic and
      intrinsic variables known to influence a fall using multiple logistic regression.
      A total of 339 types of fractures were classified, of which 16 were significantly
      associated with this BFT mechanism. Classified fracture types will augment
      anthropological interpretations of the circumstances of death from BFT in cases
      of suspected high falls.

PMID- 30107639
TI  - Functional mapping of the E. coli translational machinery using single-molecule
      tracking.
AB  - The organization of the chromosomal DNA and ribosomes in living Escherichia coli
      is compared under two growth conditions: 'fast' (50 min doubling time) and 'slow'
      (147 min doubling time). Superresolution fluorescence microscopy reveals strong
      DNA-ribosome segregation in both cases. In both fast and slow growth, free
      ribosomal subunits evidently must circulate between the nucleoid (where they
      initiate co-transcriptional translation) and ribosome-rich regions (where most
      translation occurs). Single-molecule diffusive behavior dissects the ribosome
      copies into translating 70S polysomes and free 30S subunits, providing separate
      spatial distributions for each. In slow growth, ~21,000 total 30S copies/cell
      comprise ~65% translating 70S ribosomes and ~35% free 30S subunits. The ratio of
      70S ribosomes to free 30S subunits is ~2.5 outside the nucleoid and ~0.50 inside
      the nucleoid. This new level of quantitative detail may motivate development of
      comprehensive, three-dimensional reaction-diffusion models of ribosome, DNA, mRNA
      and RNAP spatial distributions and dynamics within the E. coli cytoplasm.

PMID- 30107640
TI  - The effect of corneal infiltrates on densitometry and higher-order aberrations.
AB  - BACKGROUND: This study aimed to measure the effects of persistent corneal
      subepithelial infiltrates associated with epidemic keratoconjunctivitis on
      corneal densitometry and total corneal higher order aberrations (HOAs), and to
      compare these measurements with the data obtained from their fellow unaffected
      healthy eyes. METHODS: This prospective cross-sectional study included those who
      had persistent subepithelial infiltrates in only the affected eyes for at least
      three months and clinically normal fellow unaffected eyes. Corneal densitometry
      was measured with the densitometry software of the Pentacam HR-Scheimpflug
      corneal topographer over a 12 mm diameter of cornea. Further, total corneal HOAs
      including coma (Z[1,3], Z[3,-1]), trefoil (Z[3], Z[3,-3]), spherical aberration,
      higher order root mean square (HO-RMS), and total RMS in the Zernike analysis
      were analysed by the same Pentacam HR device. RESULTS: Forty-six eyes of 23
      participants were analysed in this study. The mean corneal densitometry values
      were statistically significantly higher in all annular concentric areas (0-2, 2
      6, 6-10, and 10-12 mm) of the anterior and central corneal layers in the eyes
      with subepithelial infiltrates when compared to normal fellow eyes (p < 0.05, for
      each one). Additionally, there were statistically significant differences between
      the eyes with subepithelial infiltrates and normal fellow eyes with regard to
      coma, trefoil, HO-RMS, and total RMS in the Zernike analysis (p < 0.05, for each
      one). CONCLUSION: This study quantitatively demonstrated that persistent corneal
      subepithelial infiltrates associated with epidemic keratoconjunctivitis decrease
      corneal transparency and corneal optical quality in affected eyes.

PMID- 30107641
TI  - A randomized usability assessment of simulated naloxone administration by
      community members.
AB  - BACKGROUND AND AIMS: Expanded access to naloxone has been identified as a key
      intervention for reducing opioid-related morbidity and mortality. It is not known
      which naloxone device will result in rapid, successful administration when
      administered by community members. The aims of this study were to estimate and
      compare (1) the rate of successful administration and (2) time to successful
      administration for single-step nasal spray, multi-step atomized nasal spray and
      intramuscular simulated naloxone by community members. DESIGN: A prospective,
      single-site, open-label, randomized usability assessment of simulated naloxone
      administration in a convenience sample of community members. Participants were
      randomized to single-step nasal spray (SP), multi-step atomized nasal spray (AT)
      or intramuscular simulated (IM) naloxone and asked to administer the simulated
      medication to a mannequin after completing a 2-minute training video. SETTING:
      New York, USA at a state fair that attracts between 60 000 and 120 000
      individuals daily. PARTICIPANTS: A total of 138 participants completed the study
      over a 2-day period in September 2016. All participants were at least 18 years of
      age and had no prior naloxone training. MEASUREMENTS: The rate of successful
      administration and time to successful administration were recorded for each
      device. FINDINGS: The SP device (100%; P < 0.001) had a higher rate of success
      compared with the IM device (69.6%). Although success differed between the AT
      (89.1%) device and IM device, as well as the AT device and SP device, these
      differences were not significant. The SP device also had a shorter median time to
      successful administration (34.3 sec) compared with the IM (99.9 sec; P < 0.001)
      and AT (110.3; P < 0.001) devices. CONCLUSIONS: After video training, community
      members are able to (1) administer single-step nasal spray naloxone with a higher
      rate of success than intramuscular naloxone in a simulated overdose setting and
      (2) administer single-step nasal spray naloxone more rapidly than both
      intramuscular and multi-step atomized nasal spray naloxone.

PMID- 30107642
TI  - A Preliminary Study of the Reliability of Anatomical Facial Landmarks Used in
      Facial Comparison.
AB  - Anatomical landmarks are considered the most objective indicators for use in
      forensic facial comparisons. Therefore, accurately identifying and locating these
      landmarks is the beginning of reliable facial comparison. This study evaluated
      the accuracy with which facial landmarks are located and examined their
      reliability according to type of landmark, head posture, and image quality. Nine
      operators located a series of landmarks on prepared facial images used to produce
      comparison images. Then, the average distances between the reciprocal landmarks
      (ADRL) on the reference and the comparison images were measured as indicators of
      landmark reliability. We found that a set of landmarks had higher or lower
      reliability as a function of the head angle and image quality. More reliable
      landmarks were associated with certain head postures and degrees of image
      quality. These should be used for facial comparison analysis depending on various
      head and image conditions.

PMID- 30107643
TI  - Interplay between RGS2 and childhood adversities in predicting anxiety and
      depressive disorders: Findings from a general population sample.
AB  - BACKGROUND: It remains unresolved whether childhood adversities interact with
      genetic variation in regulator of G-protein signaling 2 (RGS2) rs4606 in
      predicting various anxiety and depressive disorders and whether diagnostic
      specificity exists in these interactions. METHODS: The genotype of RGS2 rs4606
      was determined for N = 2,263 adults with European ancestry from the Study of
      Health in Pomerania. Lifetime anxiety and depressive disorders according to the
      Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were
      assessed with the Munich Composite International Diagnostic Interview (DIA-X/M
      CIDI). Childhood adversities were assessed with the Childhood Trauma
      Questionnaire (CTQ, when participants were aged 29-89). RESULTS: Logistic
      regressions adjusted for sex and age revealed that rs4606 interacted with total
      childhood adversity in predicting each diagnostic outcome except for panic
      disorder and generalized anxiety disorder, uncorrected and corrected for multiple
      testing (odds ratio [OR] = 1.06-1.16). That is, carriers of the GG (vs. CC/CG)
      genotype were at decreased risk for anxiety and/or depression in the presence of
      low, but at increased risk in the presence of high total childhood adversity.
      Respective gene-environment (G * E) interactions were found for (a) comorbid
      anxiety and depressive disorders (OR = 1.13), but neither pure anxiety nor pure
      depressive disorders and (b) pure/temporally primary anxiety disorders (OR =
      1.07), but not pure/temporally primary depressive disorders. The G * E
      interaction remained associated with depressive disorders after introducing
      pure/temporally primary anxiety disorders as additional predictor (OR = 1.09).
      CONCLUSIONS: rs4606 alters the risk of developing a range of anxiety but also
      depressive disorders after childhood adversities. A complex risk pattern of
      genotype, environmental factors, and preexisting anxiety contributes to
      subsequent depression development.

PMID- 30107644
TI  - Genomic landscape and mutational impacts of recurrently mutated genes in cancers.
AB  - BACKGROUND: Cancer genes tend to be highly mutated under positive selection.
      Better understanding the recurrently mutated genes (RMGs) in cancer is critical
      for explicating the mechanisms of tumorigenesis and providing vital clues for
      therapy. Although some studies have investigated functional impacts of RMGs in
      specific cancer types, a comprehensive analysis of RMGs and their mutational
      impacts across cancers is still needed. METHODS: We obtained data from The Cancer
      Genome Atlas (TCGA) and calculated mutation rate of each gene in 31 cancer types.
      Functional analysis was performed to identify the important signaling pathways
      and enriched protein types of RMGs. In order to evaluate functional impacts of
      RMGs, differential expression, survival, and pairwise mutation patterns analyses
      were performed. RESULTS: Totally, we identified 897 RMGs and 624 of them were
      specifically mutant in only a single cancer type. Functional analysis
      demonstrated that these RMGs were enriched in hydrolases, cytoskeletal protein,
      and pathways like MAPK, cell cycle, PI3K-Akt, ECM receptor interaction, and
      energy metabolism. The differentially expressed genes potentially affected by the
      same common RMG showed a relatively low overlap across different cancer types.
      For the 19 Mucin (MUC) family genes, nine of them were RMGs and four of them
      (MUC17, MUC5B, MUC4, and MUC16) were common RMGs shared in 8 to 17 cancer types.
      The results showed that recurrent mutations in MUC genes were significantly
      associated with better survival prognosis. Only a small part of RMGs was
      differentially expressed due to their own mutations and most of them were
      downregulated. In addition, pairwise mutation pattern analysis revealed the high
      frequency of co-occurred mutations among RMGs in STAD. CONCLUSION: Through the
      functional analysis of RMGs, we found that six signaling pathways were disrupted
      in most cancer types and that energy metabolism was abnormal in tumors. The
      results also revealed a strong correlation between recurrently mutated genes from
      MUC family and human survival. In addition, gene expression and survival
      prognosis were associated with different mutation types of RMGs.

PMID- 30107645
TI  - Review article: Antiemetics in the pre-hospital setting: A systematic review of
      efficacy and safety.
AB  - Antiemetics are medications that are frequently used in the pre-hospital setting.
      However, recent evidence indicates that antiemetics are ineffective in reducing
      undifferentiated nausea scores and vomiting rates. The aim of this study is to
      evaluate the efficacy and safety of antiemetics administered in the pre-hospital
      setting. This is a systematic review employing PRISMA guidelines of seven studies
      selected that included randomised controlled trials and prospective studies,
      investigating the use of antiemetics in the pre-hospital setting. Nausea scores,
      vomiting rates and rates of adverse effects along with other variables were
      summarised. Searches of PubMed, MEDLINE, CINAHL and InformIT yielded seven
      relevant full text articles. Trials that investigated the efficacy of all
      antiemetics in the pre-hospital setting were included in the search results.
      Overall, it was found that antiemetics were effective in reducing nausea and
      vomiting rates in the pre-hospital setting on initial evaluation. The antiemetics
      included in the studies were associated with insignificant or self-limiting side
      effects. However, after further examination, the reliability of the preliminary
      results can be questioned because of the poor quality of all the studies
      reviewed. There is insufficient evidence to establish the efficacy of antiemetics
      in the pre-hospital setting despite their safety. Further rigorous studies,
      preferably randomised and double blinded control trials are required to establish
      the efficacy of antiemetics in the pre-hospital setting. Consequently,
      antiemetics should be used more selectively and reserved for severe nausea and
      intractable vomiting in the pre-hospital setting. PROSPERO registration number:
      CRD42016044090.

PMID- 30107646
TI  - Severe hyponatremia complicated by seizure following 3,4
      methylenedioxymethamphetamine ingestion.

PMID- 30107647
TI  - Ethylenediurea (EDU) mitigates the negative effects of ozone in rice: Insights
      into its mode of action.
AB  - Monitoring of ozone damage to crops plays an increasingly important role for the
      food security of many developing countries. Ethylenediurea (EDU) could be a tool
      to assess ozone damage to vegetation on field scale, but its physiological mode
      of action remains unclear. This study investigated mechanisms underlying the
      ozone-protection effect of EDU in controlled chamber experiments. Ozone sensitive
      and tolerant rice genotypes were exposed to ozone (108 ppb, 7 hr day-1 ) and
      control conditions. EDU alleviated ozone effects on plant morphology, foliar
      symptoms, lipid peroxidation, and photosynthetic parameters in sensitive
      genotypes. Transcriptome profiling by RNA sequencing revealed that thousands of
      genes responded to ozone in a sensitive variety, but almost none responded to
      EDU. Significant interactions between ozone and EDU application occurred mostly
      in ozone responsive genes, in which up-regulation was mitigated by EDU
      application. Further experiments documented ozone degrading properties of EDU, as
      well as EDU deposits on leaf surfaces possibly related to surface protection. EDU
      application did not mitigate the reaction of plants to other abiotic stresses,
      including iron toxicity, zinc deficiency, and salinity. This study provided
      evidence that EDU is a surface protectant that specifically mitigates ozone
      stress without interfering directly with the plants' stress response systems.

PMID- 30107648
TI  - [Review and outlook of the eye health in China].
AB  - Eye health is a new concept that has been put forward in recent years as a result
      of the long term practice of prevention and treatment of blindness. The full
      understanding of the origin, goal and value of eye health is of great
      significance for promoting the prevention and treatment of eye diseases and the
      development of ophthalmology in China. In the past several decades, China has
      made great achievements in the development of eye health, while some challenges
      still remained. We should learn the actual requirements of the prevention of
      blindness and visual impairment and the public eye care, focus effectively on the
      major tasks, set explicit goals, gradually promote the development of eye health
      cause. At present, avoidable cataract blindness and visual impairment and un
      corrected refractive error are the key eye diseases, while persons aged 50 years
      or above are the population that needs special attention in terms of eye health.
      We should continue to strive for greater achievements in the cause of eye health.
      (Chin J Ophthalmol, 2018, 54:561-564).

PMID- 30107649
TI  - [Changes of eye care use among rural adults under the reform of New Rural
      Cooperative Medical Scheme: the Handan Eye Study].
AB  - Objective: To assess the utilization of eye care services in the rural area of
      Handan, China under the New Rural Cooperative Medical Scheme, and to analyze the
      factors associated with the uptake of these services. Methods: In a cohort
      population-based study, subjects who joined both the baseline (2006-2007) and
      follow-up (2012-2013) were included. Information of demographic characteristics,
      participation in the New Rural Cooperative Medical Insurance and use of eye care
      services, comprehensive ophthalmic examinations, blood pressure and fasting was
      collected. The protocol got approved by the ethics committee of Beijing Tongren
      Hospital, and each subject signed the informed consent. Results: Of 5 193
      eligible participants, 549 [10.6%; 95% confidence interval (CI), 9.8%-11.4%] had
      used eye care services, and the prevalence had no significant difference from
      baseline surveys (P=0.20). The municipal hospitals undertook 50.1% of eye care
      services. "No need" (4 422, 95.2%) was the most common reason cited for not using
      an eye care service; 2 875 (65.0%) of these participants had at least one type of
      eye diseases, 3 505 (79.3%) had at least one type of ocular complaints. In the
      multiple binary logistics regression model, participants who were elder [adjusted
      odds ratio (OR), 1.319; 95%CI, 1.177-1.478], were female (adjusted OR, 1.466;
      95%CI, 1.085-1.981), had a diabetes history (adjusted OR, 1.930; 95%CI, 1.381
      2.696), had a low income (adjusted OR, 0.826; 95%CI, 0.688-0.922), had ocular
      complaints (adjusted OR, 3.556; 95%CI, 2.484-5.091), had refractive errors
      (adjusted OR, 1.256; 95%CI, 1.007-1.567), had visual impairment (adjusted OR,
      4.398; 95%CI, 2.667-7.253) or had cataract (adjusted OR, 1.278; 95%CI, 1.013
      1.612) were more likely to take an eye care service. Conclusions: Under the New
      Rural Cooperative Medical Scheme, the prevalence of New Rural Cooperative Medical
      Insurance was increased significantly, but the rate of eye care use in the rural
      area was still low. Further efforts towards higher quality medical service in
      county hospitals and village clinics as well as better education about eye
      disease among the rural population may raise the eye care use in rural areas.
      (Chin J Ophthalmol, 2018, 54:570-579).

PMID- 30107650
TI  - [Analysis of cataract surgery cases from 2013 to 2015 in Shanghai].
AB  - Objective: To analyze the changes of cataract surgery volume and related
      influencing factors in Shanghai during 2013 and 2015. Methods: The information of
      Cataract patients during the period of 2013 and 2015 was collected from Shanghai
      Cataract Operations Database. The cataract surgery volume and CSR of Shanghai
      residents and non-registered ones were compared. The cataract surgery volume and
      CSR of registered Shanghai residents in urban, suburban and exurban areas were
      calculated, respectively. In addition, the sources of surgery cost, hospitals
      where surgeries were performed were analyzed. Results: In Shanghai, the cataract
      surgery volume grew from 63 915 to 114 688 and the total CSR grow from 2 686 to 4
      729 during the years between 2013 and 2015. In this period, the cataract surgery
      volume of registered Shanghai residents in urban, suburban and exurban areas
      increased from 27 203, 21 921, 8 847 to 46 415, 40 463, 18 171, respectively. The
      CSR1 (CSR of registered Shanghai residents) grew rapidly from 4 081 to 7 363,
      while the CSR2 (CSR of non-registered Shanghai residents) grew slowly from 619 to
      949. According to statistics, 93.08% of the registered Shanghai residents paid
      the medical expenses with their medical insurance, while more than 80% non
      registered Shanghai residents afforded it at their own expenses. The number of
      total CSR in urban, suburban and exurban areas increased from 5 085, 3 600, 3 205
      to 3 600, 6 588, 6 513 respectively. In 2015, the number of cataract surgery
      cases in non-public hospitals exceeded that in public hospital, accounting for
      54.71% of the total cataract surgeries. In the same year, 55.44% of the total
      cases come from suburban and exurban residents. Conclusions: From 2013 to 2015,
      there had been a dramatic increase in cataract surgery volume in nonpublic
      hospitals and exurban area in Shanghai, which effectively solved the problem of
      low CSR in suburban and exurban area, however the 1ow level of CSR of non
      registered Shanghai residents was the key factor that significantly reduced the
      total CSR in Shanghai. (Chin J Ophthalmol, 2018, 54:580-585).

PMID- 30107651
TI  - [Senile eye disease screening program in downtown Wenzhou: intraocular pressure].
AB  - Objective: To investigate the distribution and related factors of intraocular
      pressure (IOP) in the screened population aged over 50 years in Wenzhou. Methods:
      This study included 31 170 community residents aged 50 years or older in Wenzhou
      undergoing screening from March 2014 to January 2016. Participants underwent a
      complete ocular examination, including visual acuity, eye-ground photography,
      slit lamp and standardized measurement of IOP by non-contact tonometry. Subjects
      who had undergone ocular operation or laser peripheral iridectomy, had glaucoma,
      corneal or other ocular diseases that could possibly affect the IOP, had an IOP
      lower than 6 mmHg(1 mmHg=0.133 kPa) and visual acuity less than 0.3, or had
      monocular IOP values were excluded. The relationship between IOP and various
      parameters were analyzed. Results: A total of 20 875 subjects (6 902 males and 13
      973 females) were enrolled in the current analysis, including 18 677 healthy
      persons and 2 125 glaucoma suspects, with an average age of (67.3+/-8.7) years
      old. The mean IOP (mean+/-standard deviation) of the healthy population was
      (13.5+/-3.0) mmHg (13.4+/-3.2) mmHg in right eyes and (13.6+/-3.3) mmHg in left
      eyes; 2.04% of the left eyes, 1.51% of the right eyes and 2.92% of either eyes of
      healthy population had an IOP >21 mmHg. The mean IOP in glaucoma suspects was
      significantly higher than that in the healthy population (P<0.001); 6.78% of the
      left eyes, 6.16% of the right eyes and 9.65% of either eyes of glaucoma suspects
      had an IOP >21 mmHg. Men had lower IOPs than women [healthy population: (12.9+/
      3.2) mmHg versus (13.7+/-3.2) mmHg; P<0.05]. The linear function of IOP (Y) with
      age (X(1)) and the vertical cup disc ratio (X(2)) was ^Y=15.962
      0.043X(1)+0.837X(2)(P<0.05) in the healthy population. Conclusion: The IOP among
      healthy persons aged over 50 years living in downtown Wenzhou was decreased with
      age but increased with the vertical cup disc ratio. The IOP in females was higher
      than that in males. About 3% of the healthy population had an IOP greater than 21
      mmHg. (Chin J Ophthalmol, 2018, 54: 586-592).

PMID- 30107653
TI  - [The current situation of ophthalmologic examination and treatment of diabetic
      patients in a community of Fushun].
AB  - Objective: To investigate the attainment of therapeutic targets for glycosylated
      hemoglobin and blood pressure, ophthalmologic examination, diagnosis and
      treatment of diabetic retinopathy (DR) with type 2 diabetes mellitus. Methods: A
      cross-sectional study in type 2 diabetic patients was conducted in a community of
      Fushun between July 2012 and May 2013. Questionnaire, detailed ophthalmic
      examination and laboratory tests were completed to collect the information about
      sociodemographic and healthcare characteristics. Results: A total of 2 033
      eligible patients with complete information were screened from 2 224 type 2
      diabetic patients. Of them, the control rates of glycosylated hemoglobin(<7.0%),
      blood pressure[<140/80 mmHg (1 mmHg=0.133 kPa)] and serum lipid were 39.7%, 31.0%
      and 2.6%, respectively. Only 22.3% of the participants had ophthalmologic
      examination after the diagnosis of diabetes mellitus, and 72.2% of the
      participants in the study reported never receiving any recommendation for eye
      examinations from their physicians. The prevalence of DR was 44.3% in the study
      population, 27.1% receiving ophthalmologic examination ever. Among them, 213
      patients had vision-threatening DR and required laser treatment or vitreous
      surgery, but 82.2% had not been treated. Conclusions: The investigation of the
      type 2 diabetic patients in a community of Fushun indicated that more than 60% of
      patients did not attain therapeutic targets for glycosylated hemoglobin, and 70%
      for blood pressure; 78% had not received ophthalmologic examination after the
      diagnosis of diabetes mellitus; 82% of vision-threatening DR patients had not
      been treated. Educational efforts should be aimed at improving knowledge of and
      compliance with these guidelines among both internists and eye care providers.
      (Chin J Ophthalmol, 2018, 54: 599-604).

PMID- 30107652
TI  - [Retinal image quality in northern rural Chinese adult population].
AB  - Objective: To assess the retinal image quality of the normal northern rural
      Chinese adult population. Methods: A normal population-based, cross-sectional
      study. From Oct, 2012 to Jan 2013, a clustered, random sampling procedure was
      used to select normal population who visual acuity<= 0(LogMAR) and 30-69 years
      old from 2 villages. All eligible subjects were invited to undergo a
      comprehensive eye examination, and the retinal image quality related index were
      examined with pupil 4 mm using objective optical quality analysis systemII(OQAS
      II, Visiometrics, Spain), including MTFcutoff, VA20, VA9, PSF50, PSF10, OSI, SR.
      And describe the retinal image quality of different age group, including 30-39y,
      40-49y, 50-59y, 60-69y. Results: Among 1 108 participants (61.9%) that completed
      examinations in our center, 681 participants (1 362 eyes) were recruited. There
      were 146, 586, 440 and 190 eyes in each group. The spherical equivalent
      refraction of each group was (-0.35+/-0.84), (-0.19+/-0.50), (-0.03+/-0.54) and
      (0.20+/-0.71) D. The best corrected vision acuity of each group was -0.02+/-0.04,
      -0.01+/-0.03, -0.01+/-0.02 and -0.00+/-0.01. The MTFcutoff of each group was
      (37.06+/-9.31), (36.69+/-8.93), (36.52+/-9.05) and (32.61+/-10.08) c/deg. Retinal
      imaging parameters were significantly different(MTFcutoff: MD=4.45, SR:MD=0.03,
      PSF50: MD=-0.45, PSF10: MD=-2.87, VA20:MD=0.13, A9:MD=0.09, OSI:MD=-0.41,
      P<0.001)between aged 30-39 group and aged 60-69 group. Objective scattering index
      (OSI) were significantly different(MD=-0.13, P=0.004)between aged 30-39 group and
      aged 50-59 group. Retinal imaging parameters were significantly
      different(MTFcutoff:MD=4.45, SR:MD=0.03, PSF50:MD=-0.45, PSF10:MD=-2.87,
      VA20:MD=0.13, VA9: MD=0.09, OSI: MD=-0.41, P<0.001)between aged 40-49 group and
      aged 60-69 group. Retinal imageing parameters were significantly
      different(MTFcutoff: MD=4.45, SR: MD=0.03, PSF50: MD=-0.45, PSF10: MD=-2.87,
      VA20:MD=0.13, VA9:MD=0.09, OSI:MD=-0.41,P<0.001)between aged 50-59 group and aged
      60-69 group. Conclusion: Retinal image quality was gradually worse over time in
      the northern rural Chinese adult population. (Chin J Ophthalmol, 2018, 54:593
      598).

PMID- 30107654
TI  - [Prevalence status and influencing factors of visual impairment in the elderly
      people in rural areas of Yugan County, Jiangxi Province].
AB  - Objective: To assess the prevalence of visual impairment and the influencing
      factors among rural residents aged 60 years and above in Yugan county, Jiangxi
      province. Researchers analyzed influencing factors and provided scientific
      rationale for blindness prevention and control. Methods: Stratified cluster
      random sampling was used in randomly selecting 3 789 rural residents aged >= 60
      in Yugan county. Eligible residents were invited to receive ophthalmic
      examinations and epidemiological investigations. Multivariate logistic regression
      was performed to analyze any influencing factors. Results: Three thousand seven
      hundred and eighty-nine rural residents completed the ophthalmic examination and
      investigation. Based on presenting visual acuity, the prevalence of visual
      impairment was 24.1%(915), of which blindness and moderate and severe was
      2.9%(108) and 21.3%(807). The top five causes ranked are (1) cataract (283,
      30.9%), (2) Refractive error (81, 8.9%), (3) macular degeneration (29, 3.2%), (4)
      Corneal opacity (14, 1.5%). Multivariate logistic regression showed that age,
      gender, education, occupation, marital status, ophthalmic anamnesis, smoking
      situation, and daily fruit intake were the main factors that were the influencing
      factors of visual impairment. Conclusions: The prevalence of visual impairment in
      the elderly population in rural areas of Yugan County is quite high. Keep a
      healthy diet, timely correction of eye disease, could reduce the risk of visual
      impairment. (Chin J Ophthalmol, 2018, 54:605-610).

PMID- 30107655
TI  - [Analysis of the quality of life and the influencing factors in patients with
      diabetic retinopathy before and after receiving pan-retinal photocoagulation].
AB  - Objective: Quality of life and the influencing factors in patients with diabetic
      retinopathy before and after receiving treatment of pan-retinal photocoagulation
      (PRP) were studied. Methods: Prospective study. A total of 55 diabetic
      retinopathy patients were collected at Beijing Friendship Hospital, Capital
      Medical University from November 2016 to August 2017 and were surveyed using
      Vision Function Questionaire (VFQ-25) to evaluate their quality of life before
      and 3 months after treatment with PRP. According to diagnostic criteria, the
      patients were divided into two groups: severe nonproliferative diabetic
      retinopathy(NPDR) and proliferative diabetic retinopathy group(PDR). SPSS was
      used for statistical analysis. Results: The score of VFO-25 general health before
      PRP treatment was 62.73+/-14.20, obviously lower the other sub scale scores of
      VFO-25. The results of variance analysis there was significant statistical
      difference between the composite score and the different educational levels
      (F=2.94, P<0.05), but there was no statistical difference for diabetes duration
      (F=3.01, P<0.05). The composite score was significantly significance between the
      severe NPDR and PDR group(t=8.95, P<0.05). The patients with hyperlipidemia (t=
      3.21, P<0.05), hypertension(t=-2.32, P<0.05) and renal insufficiency(t=-2.05,
      P=0.045) has lower composite score. There was high relationship for age among the
      factors of worse logMAR vision, better logMAR vision and age (r=-0.47, P<0.05; r=
      0.38, P<0.05; r=-0.26, P<0.05). The scores of VFQ-25 subscale of social function
      (t=-2.07, P<0.05) , role limitations (t=-2.38, P<0.05) , dependency (t=-2.99,
      P<0.05) and mental health (t=-2.26, P<0.05) was significantly increased after
      treatment of PRP. The score of ocular pain was obviously decreased (t=4.19,
      P<0.001) ; there were no significance in other sub scale scores. Conclusions:
      This study showed that the degree of visual acuity, the severity of DR and age
      were an important factor affecting the quality of life in DR patients. PRP
      therapy could improve the mental health and social field of DR patients, but
      failed to improve the scores of other visual functions in the patients. (Chin J
      Ophthalmol, 2018, 54:611-616).

PMID- 30107656
TI  - [Pathophysiology and therapeutic progress of diabetic macular edema].
AB  - Diabetic macular edema (DME) is the leading cause of vision loss in diabetics.
      The destruction of blood retinal barrier is the primary pathological feature. At
      present, a large number of animal experiments and clinical studies show that DME
      not only has abnormal vascular structure, but also is an inflammatory disease. A
      variety of inflammatory media and chemokine are involved in the process of DME.
      With the extensive clinical application of anti-vascular endothelial growth
      factor (VEGF), the treatment of DME got a revolutionary breakthrough. However,
      unlike proliferative diabetic retinopathy (PDR), DME patients response
      intensively to anti-VEGF agents and couldn't resolve completely despite of
      multiple injections. Therefore, in addition to VEGF, other possible therapeutic
      targets and clinical trials of new drugs are also widely carried out. This
      article reviews the therapeutic process of DME. (Chin J Ophthalmol, 2018, 54: 625
      630).

PMID- 30107657
TI  - [Research progress of hydrogen-rich saline for eye diseases].
AB  - As an antioxidant, hydrogen-rich water has been widely studied in recent years.
      It is mild enough neither to disturb metabolic redox reactions nor to affect
      signaling reactive oxygen species. Therefore, there should be no or few adverse
      effects of H(2). Numerous studies in biology and medicine show that hydrogen-rich
      water has achieved good results in nervous system, digestive system, respiratory
      system, heart and kidney diseases. At present, there are few studies on the
      treatment of eye diseases with hydrogen-rich water. This review summarizes the
      research progress of hydrogen-rich water for eye diseases in the domestic and
      foreign literatures. (Chin J Ophthalmol, 2018, 54: 631-635).

PMID- 30107658
TI  - [Clinical research progress of gene therapy for Leber hereditary optic
      neuropathy].
AB  - Leber hereditary optic neuropathy (LHON) is a mitochondria hereditary eye disease
      that involves with retinal ganglion cells (RGCs) resulting eventually in
      degeneration and atrophy of optic nerve. The three mitochondrial DNA mutations
      (ND4 G11778A, ND1G3460A, ND6T14484C) have been recognized as the primary mutation
      locus of LHON. Currently there is no effective therapy for LHON. The result of a
      clinical trial launched in 2007 indicated that intraocular injection of the
      recombination of adeno-associated virus and target gene is an effective and safe
      cure for Leber's Congenital Amaurosis (LCA), which brings hope of treating other
      hereditary eye diseases with gene therapy. Since LHON mainly involves with RGCs,
      the target gene can be delivered directly to RGCs with the means of injecting the
      recombination into vitreous cavity, therefore resulting in less damage to retina
      as compared to other gene therapy for LCA which require the drug to be injected
      under the retina. This article summarizes the research progress of the clinical
      trial relevant to gene therapy for LHON. (Chin J Ophthalmol, 2018, 54: 636-640).

PMID- 30107659
TI  - [Xp11 translocation RCC and the mesenchymal counterparts: an update].

PMID- 30107660
TI  - [Clinicopatholigic features of renal cell carcinoma associated with chromosome X
      inversion harboring gene fusions involving TFE3].
AB  - Objective: To study the clinicopathologic features, immunophenotype,
      characteristic FISH pattern and prognosis of renal cell carcinoma (RCC)
      associated with chromosome X inversion harboring gene fusions involving TFE3.
      Methods: Ten cases of NONO-TFE3 RCC and four cases of RBM10-TFE3 RCC were
      investigated at Nanjing Jinling Hospital from 2009 to 2016 by clinicopathological
      findings, immunohistochemistry, and genetic analysis. Results: Morphologically,
      the distinct pattern of secretory endometrioid subnuclear vacuolization was
      overlapped with clear cell papillary RCC, and often accompanied by sheets of
      epithelial cells in NONO-TFE3 RCC. Most cases of RBM10-TFE3 RCC presented with
      the biphasic feature that acinar, tubular and papillary patterns of epithelioid
      cells combined with sheets of small cells with "pseudorosette-like"
      architectures. In addition, cytoplasmic vacuolization, nuclear groove, and
      psammoma bodies were also observed. Immunohistochemically, all NONO-TFE3 RCC
      cases were immunoreactive for TFE3, CD10, RCC markers, and PAX8, and negative for
      CK7, Cathepsin K, Melan A, HMB45, Ksp-cadherin, vimentin, and CD117. All 4 cases
      of RBM10-TFE3 RCC showed moderate to strong immunoreactivity for TFE3, Cathepsin
      K, CD10, Ksp-cadherin, E-cadherin, P504s, RCC marker, PAX8, and vimentin but
      negative for TFEB, HMB45 and CK7. CKpan and Melan A were at least focally
      expressed. The antibody to Ki-67 showed labeling of 3%-8% (mean 5%). There were
      some expression discrepancies of immunochemistry between different histological
      patterns. PAX8, CKpan, P504s, and Ksp-cadherin were expressed in epithelioid
      areas but not in small-cell areas. Ki-67 labeling index of epithelioid areas was
      higher than that in small-cell areas. In molecular analysis, NONO-TFE3 fusion
      transcripts were identified in 6 patients. The fusion points were between exon 7
      of NONO and exon 6 of TFE3 in 5 patients and between exon 9 of NONO and exon 5 of
      TFE3 in one patient. All 4 cases of RBM10-TFE3 RCC demonstrated to have RBM10
      TFE3 fusion transcripts and the fusion points were between exon 5 of TFE3 and
      exon 17 of RBM10. Using TFE3 break-apart FISH assay, all 10 cases of NONO-TFE3
      RCC showed characteristic patterns of equivocal split signals with a distance of
      nearly 2 signal diameters. All 4 cases of RBM10-TFE3 RCC showed colocalized or
      subtle split signals with a distance of <1 signal diameter, which was considered
      as negative results. Long-term follow-up was available for 7 patients of NONO
      TFE3 RCC and 4 patients of RBM10-TFE3 RCC. All patients were alive with no
      evidence of disease. Conclusions: Two rare genotypes, NONO-TFE3 RCC and RBM10
      TFE3 RCC, are reported in this study. Both of these two tumors show specific
      morphology and good prognosis, along with the positive TFE3 staining and the
      equivocal or false-negative TFE3 FISH results, which could be missed. PCR
      detection or next-generation sequencing can determine the genotype.

PMID- 30107661
TI  - [Clinicopathologic features of glomus tumor of the kidney].
AB  - Objective: To investigate the clinicopathologic and differential diagnostic
      features of glomus tumor of the kidney. Methods: Four cases of glomus tumor of
      the kidney were collected from the archives of Peking University Third Hospital,
      the Second Hospital of Tianjin Medical University, Ningbo Yinzhou Second Hospital
      and Zhejiang Provincial People's Hospital between January 2012 to June 2017; the
      clinical and radiologic features, histomorphology, immunohistochemistry,
      ultrastucture and prognosis were analyzed and the relevant literature was
      reviewed. Results: Patients consisted of 2 men and 2 women with ages ranging from
      37 years to 66 years (mean 55 years). Three patients had history of hypertensive
      disease (grade II, 3 to 10 years). The tumors measured in maximum diameter from
      3.0 cm to 4.0 cm (mean 3.6 cm) and showed gray-white to yellow and tan on cut
      surface. Macroscopical examinations showed all tumors were circumscribed but non
      encapsulated. Histologically, 1 tumor presented as glomus tumor with extensive
      myxoid change, 1 as cellular and solid pattern glomus tumor, 1 as glomangioma
      with focal myopericytoma-like pattern and 1 as symplastic glomus tumor with areas
      resembling myopericytoma. The tumor cells in two cases showed scant cytoplasm and
      uniform, bland-appearing nuclei without mitoses. In one case, the tumor cells
      were epithelioid with abundant eosinophilic cytoplasm and relatively well-defined
      cell borders. There was an increased mitosis of 4/50 HPF; however, no evidence of
      atypical mitosis or nuclear atypia was noted. In the symplastic glomus tumor the
      tumor cells showed frequently nuclear pleomorphism without mitoses. By
      immunohistochemistry, all tumors showed strong and diffuse reactivities to at
      least 3 of the 4 muscle-associated markers (SMA, h-Caldesmon, MSA and Calponin),
      3 tumors strongly and diffusely expressed collagen IV, 2 expressed CD34 and 1
      focally expressed desmin; whereas markers including epithelial, neuroendocrine,
      nephrogenic, melanoma-associated, STAT6, S-100 protein, CD117 and beta-catenin
      all were negative in all the 4 tumors. Ultrastuctural analysis was done in 2
      cases and showed prominent cytoplasmic actin bundles and pericellular basement
      membrane, and lacking of rhomboid renin crystals in both tumors. The hypertension
      persisted after surgical resection for all the 3 patients with this medical
      history. Follow-up information (range: 6-64 months, mean: 44 months)showed that
      no evidence of local recurrence or distant metastasis was identified in all 4
      patients. Conclusions: Glomus tumor rarely occurs in the kidney and usually has a
      good prognosis. Careful attention to its morphology with the judicious use of
      immunohistochemistry and ultrastuctural analysis can be helpful for its diagnosis
      and differential diagnosis.

PMID- 30107662
TI  - [Clinicopathologic features and immunophenotype of pseudosarcomatous
      myofibroblastic proliferation of urinary bladder].
AB  - Objective: To investigate the clinicopathologic features, immunohistochemical
      phenotypes and biological behavior of pseudosarcomatous myofibroblastic
      proliferation (PMP) of the urinary bladder which may be misdiagnosed as a
      malignant neoplasm and undergo extensive treatment. Methods: Six cases of PMP of
      the urinary bladder were collected from 2001 to 2016 at Beijing Tiantan Hospital,
      Capital Medical University. The clinicopathologic features and immunophenotypic
      profile were studied by histopathological and immunohistochemical investigations
      with clinical follow-up. At the same time, the translocation of ALK gene was
      detected by fluorescence in situ hybridization (FISH). Immunohistochemistry was
      carried out using EnVision method for the expression of AE1/AE3, vimentin, EMA,
      SMA, Caldesmon, Calponin, desmin, ALK, Ki-67, MyoD1, myoglobin, CD34, S-100,
      CD117, CK7, CK20, GATA3, p63 and CK5/6. The related literature was reviewed.
      Results: There were two male and four female patients, significantly more common
      in women. The age of the patients was 27 to 53 years, and the median age was 35
      years. The main clinical symptom was painless gross hematuria, one case with
      dysuria, and one case showed recurrent cystitis. There was no history of surgery
      and trauma. Follow-up ranged from 4 months to 13 years and showed five cases
      without recurrence and one case with recurrence. Microscopy showed submucosal
      lesion with inflammatory exudate and bleeding on the surface, in some cases
      extending to the superficial muscles of the bladder wall. The lesion was
      characterized by the proliferation of plump spindle cells, which were loose or
      dense in arrangement. There were varying degrees of acute and chronic
      inflammatory cells infiltration in the myxoid matrix. Spindle cells arranged in
      disorder, or a dense stranding, especially abundant in the cell region. The
      median mitotic rate was <2/10 HPF cells, but there were no pathological mitotic
      figures and without nuclear atypia in most spindle cells. Spindle cells with
      eosinophilic cytoplasm showed long tapering cytoplasmic projections. Oval or
      short spindle nuclei had vacuolization with prominent nucleoli, looking like
      ganglionic cells. There were scarce collagen fibers, and a few spindle cells
      degenerated with chromatin blurred. Some areas showed a granuloma-like pattern
      and neutrophils within vascular cavity. Immunohistochemically, the spindle cells
      were diffusely positive for vimentin, SMA and caldesmon. CKpan was strongly and
      diffusely positive. Desmin and calponin expression was varying. Ki-67 positive
      cells were about 35% to 55%, but the spindle cells were negative for myoglobin, S
      100, CD117, CD34, p63 and CK5/6. FISH test showed that there was no ALK isolated
      signal in 6 cases of PMP, and so no positive cases were found. Conclusions: PMP
      of the urinary bladder is a benign non-neoplastic myofibroblastic proliferative
      lesion. Morphology is extremely easy to be misdiagnosed as malignant tumors, and
      therefore more attention should be paid to avoid this misdiagnosis.

PMID- 30107663
TI  - [Comparison of different massive parallel sequencing platforms for mutation
      profiling in formalin-fixed and paraffin-embedded samples].
AB  - Objective: To compare the performance of Miseq and Ion Torrent PGM platforms and
      library construction method for next-generation sequencing (NGS) technology for
      formalin-fixed and paraffin-embedded (FFPE) samples. Methods: A total of 204 FFPE
      cancer samples including 100 non-small cell lung cancers at the First Affiliated
      Hospital of Zhejiang University, and 104 colorectal cancers at West China
      Hospital of Sichuan University were retrospectively selected from January 2013 to
      December 2016. By using the same samples, DNA was extracted, and the same amount
      of DNA was used for library construction with the same kit, and sequenced on
      Miseq and Ion Torrent PGM respectively, after passing the quality control. Any
      discordant mutations between two platforms were validated by amplified refractory
      mutation system-polymerase chain reaction (ARMS-PCR) method and Sanger
      sequencing. Results: A total of 204 FFPE samples were included and 197 samples
      were successfully analyzed by both platforms. The number of reads generated by
      the samples on Miseq platform sequencing was higher than PGM platform (median 391
      634 vs. 298 030, P<0.01). Alignment with human reference genome showed that the
      mapping rate of Miseq platform was higher than PGM platform (median 100.0% vs.
      99.7%, P<0.01). The median sequence depth of samples on Miseq was higher than PGM
      platform (median 853* vs. 698*, P<0.01). A total of 236 mutations were detected
      by two platforms, of which 221 were detected on both platforms, with a 93.6%
      concordance. Miseq platform detected 11 mutations not detected on PGM platform,
      while PGM platform detected 4 more mutations not detected on Miseq platform. With
      validation by ARMS-PCR and Sanger sequencing, Miseq platform was more reliable
      for low-frequency mutations. The main reasons for the discordant mutations
      between two platforms were that mutation frequency on undetected platform was
      lower than mutation reporting range (5%) and FFPE samples were stored for a long
      time. Conclusions: Compared with PGM, Miseq platform shows higher sequencing
      quality in terms of the number of reads, alignment results and coverage depth,
      and the test results are more reliable. In clinical practice, the appropriate
      platform should be chosen based on sample size and actual throughput requirements
      to aid in the molecular characterization of tumors.

PMID- 30107664
TI  - [Relationship between PD-L1 protein expression and gene amplification in gastric
      cancer tissues].
AB  - Objective: To investigate the relationship of PD-L1 protein expression and gene
      amplification in gastric cancer and their correlation with clinicopathologic
      factors. Methods: The cohort included 247 gastric cancer specimens with follow-up
      data and clinicopathologic data obtained from Shanxi Cancer Hospital in 2011. PD
      L1 expression was detected by immunohistochemistry (IHC) and fluorescence in situ
      hybridization (FISH). Results: PD-L1 protein was expressed in 25.9% (64/247) of
      the tumor cells and 26.7% (66/247) of the tumor infiltrating immune cells (IC).
      There was a correlation between the two (P<0.01). The expression of PD-L1 in
      tumor cells correlated with the degree of differentiation and tumor
      diameter(P<0.05). The PD-L1 expression in IC correlated with vascular tumor
      thrombi(P<0.05). The amplification rate of PD-L1 gene detected by FISH was 19.0%
      (47/247), and was associated with age, large/small curvature of the stomach,
      tumor location, tumor diameter, and lymph node metastasis(P<0.05). The positive
      coincidence rate of the two methods was 25.0% (16/64), negative coincidence rate
      was 83.0% (152/183), and total coincidence rate was 68.0% (168/247), suggesting
      that the coincidence of IHC and FISH was poor (P=0.157). There was a negative
      correlation between PD-L1 protein expression on tumor cells and prognosis in
      gastric cancer. There was no significant correlation between PD-L1 protein
      expression on IC and PD-L1 gene amplification with prognosis. Vascular tumor
      thrombi, tumor diameter, depth of invasion, and lymph node metastasis were all
      poor prognostic factors of gastric cancer(P<0.05). Multivariate Cox regression
      analysis showed that PD-L1 protein expression, depth of invasion and lymph node
      metastasis were all independent prognostic risk factors for gastric cancer.
      Conclusions: Concordance between PD-L1 protein expression and gene amplification
      is poor. PD-L1 protein expression may signify poor prognosis. There is no
      significant correlation between PD-L1 gene amplification and prognosis of
      patients with gastric cancer.

PMID- 30107665
TI  - [Lung non-terminal respiratory unit type adenocarcinoma: a clinicopathologic
      study].
AB  - Objective: To evaluate the clinicopathologic characteristics of lung non-terminal
      respiratory unit (non-TRU) type adenocarcinoma. Methods: Seventy-two cases of
      lung non-TRU type adenocarcinoma that underwent complete resection and diagnosed
      at Departments of Pathology, Affiliated Suzhou Hospital of Nanjing Medical
      University and Nanjing General Hospital of the PLA from January 2005 to December
      2016 were retrospectively studied. The histomorphological changes and precursor
      lesions were observed under microscope. The expression of lineage-specific
      markers and tumor stem cell markers was detected by immunohistochemistry (IHC).
      The major driver mutations of lung adenocarcinoma were tested by ARMS and
      directive gene sequencing. Results: Non-TRU type adenocarcinomas were more
      commonly found in male (65.3%, 47/72), former or current smokers (68.1%, 49/72),
      the elder (mean 61 years old), central adenocarcinoma (75.0%, 54/72), tumors with
      necrosis (61.1%, 44/72) and higher grade (73.6%, 53/72). Histologically, non-TRU
      type adenocarcinoma displayed complex histomorphology and was often composed of
      large irregular gland-like and acinar pattern accumulating extracellular mucin,
      necrotic tumor cell debris and neutrophils, or invasive adenocarcinoma with mucin
      production. The tumor cells were composed of bronchial surface epithelial cells,
      mucinous column cells, polygonal cells and goblet cells. Eighteen (25.0%), 23
      (31.9%) and 28 (38.9%) cases exhibited ciliated columnar cell metaplasia (CCCM),
      mucous columnar cell change (MCCC) and bronchiolar columnar cell dysplasia (BCCD)
      (precursor lesion of lung adenocarcinoma). IHC showed the expression of CK7
      (100.0%, 72/72), TTF1 (12.5%, 9/72), Napsin A (5.6%, 4/72), MUC5AC (81.9%,
      59/72), MUC5B (87.5%, 63/72), p53 (66.7%, 48/72), CK5/6 (12.5%, 9/72), p63
      (18.1%, 13/72), CK20 (19.4%, 14/72) and CDX2 (16.7%, 12/72) in the tumor cells.
      The expression of tumor stem cell markers was detected in 43.1% cases (31/72) for
      CD44, 31.9% (23/72) for CD133, 58.3% (42/72) for beta-catenin, 36.1% (26/72) for
      ALDH1, 12.5% (9/72) for GATA6, 20.8% (15/72) for SOX2 and 29.2% (21/72) for OCT4.
      The driver mutations were 26.4% (19/72) for KRAS, 2.8% (2/72) for EGFR and 1.4%
      (1/72) for EML4-ALK, and none for BRAF and ROS1. Conclusion: Non-TRU type
      adenocarcinoma is an uncommon subtype of lung adenocarcinoma with distinct
      clinicopathologic characteristics, histologic appearances, immunophenotype and
      molecular genetic alterations.

PMID- 30107666
TI  - [Clinical application of STR genotyping diagnosis for hydatidiform mole and
      nonmolar gestation].
AB  - Objective: To investigate the value of short tandem repeat (STR) genotyping in
      the diagnostic workup of molar and non-molar gestations with correlation of
      histological characteristics. Methods: Six hundred and fifty-six cases were
      selected based on clinically suspected hydropic abortion and/or molar pregnancy
      from July 2015 to September 2017 at Beijing Obstetrics and Gynecology Hospital.
      DNA was extracted from dissected chorionic villi and paired maternal endometrial
      FFPE tissue samples by Simplex OUPTM FFPE DNA Tissue Kit. STR genotyping was
      performed by PowerPlex 16 HS system. Results: DNA genotyping was informative in
      649 of 656 cases, leading to identification of 215 hydatidiform mole gestations
      and 434 non-molar gestations. Most of non-molar gestations (375 cases, 86.4%)
      were diploid hydropic abortion. Various trisomy syndromes were found (53 cases,
      12.2%), including trisomy 2, 3, 4, 7, 8, 13, 16 and 21. Only 2(0.5%) digynic
      triploid gestations were detected. Moreover, 4 cases (0.9%) of uniparental
      disomies (homologous or heterologous) were found. There were 196 cases with
      histologic diagnostic suspicious of hydatidiform moles were accurate sub
      classified. Among them, 59 cases hydatidiform moles were under-diagnosed as
      diploid hydropic abortions, and 28 cases diploid hydropic abortions were over
      diagnosed as hydatidiform moles.Compared with partial moles(PHM), there were no
      specific histomorphological features between the various types of non-molar
      gestations and partial moles for definitive diagnostic separation. There was no
      significant difference in the expression of p57(kip2) among PHM, trisomy and
      diploid hydropic abortions group (P=0.247). Conclusions: STR genotyping can
      distinguish non-molar gestations from early hydatidiform moles, and efficiently
      avoid misdiagnosis based only on histological evaluation. Therefore, using STR
      genotyping, not only can the overdiagnosis of non-molar pregnancy be avoided, but
      also individualized management can be offered to patients including monitoring of
      serum hCG.

PMID- 30107667
TI  - [Angiofibroma of soft tissue: a clinicopathologic analysis of 24 cases].
AB  - Objective: To investigate the clinicopathologic and genetic features, pathologic
      diagnosis and differential diagnosis of angiofibroma of soft tissue(AFST).
      Methods: The clinicopathologic characteristics of 24 cases diagnosed at Fudan
      University Shanghai Cancer Center from 2011 to 2017 were analyzed;
      immunohistochemical staining and interphase fluorescence in situ hybridization
      (FISH) were performed, and the literatures were also reviewed. Results: There
      were 15 male and 9 female (male?female=1.7?1.0) patients with age of onset
      ranging from 8 to 68 years (mean, 45 years). Fourteen cases occurred in
      extremities, including upper limbs (n=3) and lower limbs (n=11); seven cases were
      in the trunk, and 1 case each was in the temporal region, retroperitoneum and
      liver, respectively. Clinically, the tumors usually presented as a slowly growing
      painless mass. Tumor sizes ranged from 0.8 to 14 cm (mean 4.6 cm).
      Microscopically, most lesions were well-circumscribed, with fibrous capsules. Few
      cases infiltrated the surrounding fibrofatty tissue focally. The tumors were
      mainly composed of sparse short spindle cells and numerous small, branching, thin
      walled blood vessels distributed in amyxoid, fibromyxoid or collagenous matrix,
      often accompanied by medium-sized, round or irregular and ecstatic vessels at the
      tumor periphery.By immunohistochemistry, all tested cases expressed vimentin
      (5/5), and showed variable positivity for EMA (2/4), ER (1/2), PR (2/3), alpha
      SMA (1/18)and desmin (1/10). Ki-67 proliferation index were all less than 5%.
      CD34, CD31 and ERG staining clearly outlined the contours of blood vessels in the
      stroma. Four cases were tested for NCOA2 gene rearrangement by FISH, of which
      three were positive. Follow-up data was available in 17 patients (range, 3 to 69
      months; mean, 30 months) were all free of disease. Conclusions: Soft tissue
      angiofibroma is a benign fibroblastic neoplasm characterized by a prominent and
      complex vasculature set in a myxoid-to-collagenous stroma, and cytogenetically a
      distinctive NCOA2 gene rearrangement. Caution should be exercised for the
      possibility of potentially misinterpretation of AFST as vascular tumors and other
      myxoid soft tissue tumors.

PMID- 30107669
TI  - [Clinicopathologic characteristics of eosinophilic solid and cystic renal cell
      carcinoma].

PMID- 30107668
TI  - [Ovarian clear cell borderline tumour: a clinicopathologic analysis].
AB  - Objective: To investigate the clinical and pathological characteristics and
      prognosis of ovarian clear cell borderline tumor. Methods: A total of 12 cases of
      ovarian clear cell borderline tumors recorded were collected from May 2011 to
      December 2017 at Obstetrics and Gynecology Hospital, Fudan University.Clinical
      histories were retrieved and pathological slides were reviewed. Results: The age
      of the patients ranged from 35 to 65 years with a mean age of 52 years. Seven
      cases were associated with cystic endometriosis of the ovary. All tumors
      consisted of irregular and crowded glands or cysts embedded in a fibromatous
      stroma. The cysts and glands were lined by mild to moderate atypical cells.CK7
      and HNF-1beta were expressed in all cases, and Naspin A was expressed in 11
      cases. ARID1A expression was absent in 5 cases and p53 showed wild-type
      expression. None of the cases developed recurrence during follow-up ranging from
      7 to 79 months. Conclusions: Ovarian clear cell borderline tumor may be
      associated with endometriosis and tumor suppressor gene ARIDA. The tumor has a
      good prognosis without recurrence and progression to carcinoma.

PMID- 30107670
TI  - [Clinicopathologic analysis of primary osteosarcoma of the kidney].

PMID- 30107671
TI  - [Clinical value of methylated Septin9 in colorectal cancer].

PMID- 30107672
TI  - [Clinicopathologic and molecular subtyping analysis of occult breast cancer].

PMID- 30107674
TI  - [Comparative study on several methods for collagen a1(I) and collagen a1(III)
      measurement].

PMID- 30107673
TI  - [Improving the methods for processing specimens derived from endobronchial
      ultrasound-guided transbronchial needle aspiration so as to increase the
      pathological diagnosis accuracy].

PMID- 30107675
TI  - [Cervical metastasis succinare dehydrogenase (SDH)deficient associated renal
      carcinoma:report of a case].

PMID- 30107676
TI  - [Renal cell carcinoma with t(6;11):report of a case].

PMID- 30107677
TI  - [Hodgkin lymphoma transformation of chronic lymphocytic leukemia: report of a
      case].

PMID- 30107678
TI  - [Collision carcinoma of cervical minimal deviation adenocarcinoma and poorly
      differentiated carcinoma: report of a case].

PMID- 30107679
TI  - [Pathologic diagnosis and differential diagnosis of easily misdiagnosed lesions
      of the bladder].

PMID- 30107681
TI  - [The opportunity and challenge of the development of clinical neuroscience].

PMID- 30107680
TI  - [Progress of macrophage and tumor lymphangiogenesis].

PMID- 30107682
TI  - [Roles of rapid eye movement sleep behavior disorder in understanding the
      etiology and developing preventive strategies for Parkinson's disease].

PMID- 30107683
TI  - [The opportunities and challenges of the deep crain stimulation for Parkinson's
      Disease in the future].

PMID- 30107684
TI  - [Effect of Vascular Risk Factors on the Progression of Cognitive Dysfunction of
      Alzheimer's Disease].

PMID- 30107685
TI  - [The origin,status and future of sEEG in epilepsy surgery].

PMID- 30107686
TI  - [Neurodevelopmental hypothesis and clinical staging intervention of
      schizophrenia].

PMID- 30107687
TI  - [Brain science and depression].

PMID- 30107688
TI  - [Gut microbiota and neuropsychiatric disorders].

PMID- 30107690
TI  - [Stereotactic iodine-125 brachytherapy in the management of adult thalamic high
      grade gliomas].
AB  - Objective: To evaluate the effect of stereotactic iodine-125 brachytherapy in the
      management of adult thalamic high grade gliomas. Methods: Five cases of adult
      thalamic high grade gliomas (WHO III-IV) were treated with stereotactic iodine
      125 brachytherapy and temozolomide chemotherapy at the Second Affiliated Hospital
      of Zhejiang University School of Medicine between December 2016 and February
      2018, assisted with stereotactic plan and radiation therapy planning system.
      Results: Pathology revealed anaplastic astrocytoma (WHO III, 2 cases) and
      glioblastoma (WHO IV, 3 cases). The average amount of iodine-125 implanted was
      10.6 seeds. After surgery, the Karnofsky Performance Scale (KPS) was the same as
      preoperative KPS, and there was no severe surgery related neurological deficits.
      The follow-up time was from 2 months to 16 months, with an average of 7.8 months.
      One patient (WHO III) without chemotherapy presented with tumor progression 6.5
      months later. The other four cases showed tumor stable on MRI. Conclusions:
      Stereotactic iodine-125 brachytherapy in the management of adult thalamic high
      grade gliomas showed satisfactory recent curative effect. Large case studies and
      long follow-up are needed for further evaluation.

PMID- 30107689
TI  - [Paired comparative study of risk factors related to aneurysm rupture during
      hospitalization].
AB  - Objective: Aneurysm rupture during in-hospital period contributes to the
      exceedingly high morbidity and mortality of inpatients with untreated aneurysm.
      However, risk factors for aneurysm rupture during hospitalization were scarcely
      focused in previous reports. The aim of this study was to investigate the risk
      factors of aneurysm rupture during hospitalization and to propose clinical
      strategies improving prognosis. Methods: Patients with intracranial aneurysm (lA)
      rupture during hospitalization were identified in our prospective cohort of
      consecutive patients admitted to Beijing Tiantan Hospital between Jan 2014 to Dec
      2017. The ruptured cases were randomly paired with control cases without rupture
      during hospitalization (controlling age and gender) in a proportion of 1?2 from
      the cohort. An observational comparative study was conducted between the two
      groups. Results: Tevelve cases with IAs rupture during hospitalization were
      identified among 4 429 cases with IAs. Twenty-four control cases were matched for
      gender (male?female=5?7) and age distribution. A history of pre-hospital aneurysm
      rupture was indicated as a risk factor for IA rupture during hospitalization
      (OR=8.333, 95% CI 1.480-46.936, P=0.011). The irregular shape (OR=10.133, 95% CI
      1.941-52.902, P=0.005)and an inflow angle<60 degrees (OR=41.800, 95% CI 4.311
      405.335, P=0.000)were morphologic factors associated with IA rupture of
      inpatients. Conclusions: A history of pre-hospital IA rupture, IAs with irregular
      shape and an inflow angle <60 degrees  were risk factors associated with IAs
      rupture of inpatients. Unfavorable outcomes were observed in cases with IA
      rupture during hospitalization. A one-stage hybrid surgical strategy combining
      diagnosis, evaluation and intervention could reduce the length of preoperative
      stay, as well as the rupture risk of inpatients with IAs.

PMID- 30107691
TI  - [A single center large cohort study on perioperative complications of carotid
      endarterectomy of 547 cases].
AB  - Objective: To analyze the risk factors of perioperative complications within 30
      days of carotid endarterectomy(CEA) in the treatment of carotid atherosclerosis
      stenosis(CAS) during 2011-2017, and to discuss the techniques for reducing the
      perioperative complication rates. Methods: From August 2011 to August 2017, 486
      patients with CAS were retrospective included, and 61 of them underwent bilateral
      CEA, with a total of 547 cases of CEA included. Perioperative complications were
      collected within 30 days after operation, and the risk factors related to
      perioperative complications were analyzed by statistical analysis. Results: In
      total 547 cases, 12 cases had a postoperative stroke, while 1 case died. A total
      of 7 cases underwent cranial nerve injury, and 5 cases had an incision related
      complications. In chi-square test analysis, data suggested that there was a
      significant difference in the incidence of complications in patients with heart
      disease, preoperative neurological score difference, contralateral carotid
      serious stenosis or occlusion and intraoperative shunt in CCA/ICA technique
      application (P<0.05). In the multivariate Logistic regression, it suggested that
      poor preoperative neurological score and contralateral carotid serious stenosis
      or occlusion were independent risk factors for perioperative stroke and death.
      Conclusion: Our results showed that CEA is effective to prevent stroke and treat
      patients with CAS. Patients with poor preoperative neurological score and
      contralateral carotid serious stenosis or occlusion may increase the risk of
      postoperative stroke rates.

PMID- 30107692
TI  - [Clinical value of droplet digital polymerase chain reaction method in detecting
      plasma circulating tumor deoxyribonucleic acid epidermal growth factor receptor
      mutations in advanced pulmonary adenocarcinoma patients].
AB  - Objective: To determine the clinical value of droplet digital polymerase chain
      reaction (ddPCR) method to detect plasma circulating tumor DNA (ctDNA) epidermal
      growth factor receptor (EGFR) mutations in advanced pulmonary adenocarcinoma.
      Methods: One hundred and thirty six patients with advanced pulmonary
      adenocarcinoma diagnosed in the Beijing Chest Hospital were collected from May
      2015 to April 2017 for initial treatment. EGFR gene mutation in the plasma ctDNA
      was detected by both ddPCR and amplification refractory mutation system (ARMS)
      assays. EGFR gene mutation in the tumor tissue was detected by ARMS assay.
      Patients with EGFR sensitive mutations received first-line oral treatment with
      EGFR tyrosine kinase inhibitor (EGFR-TKI) drugs. The Kaplan-Meier survival
      analysis was used to compared the progression-free survival (PFS) in EGFR gene
      mutated patients detected with different methods. Results: Total of 111 samples
      (81.6%) were detected with EGFR gene mutations in 136 tumor tissue samples. In
      the 111 samples, 48 samples were found with exon21 L858R mutation (48/111,
      43.2%), 59 samples were found with exon19 deletion mutations (59/111, 53.2%), and
      4 cases were found with other mutations (4/111, 3.6%). Using tumor specimens as
      the gold standard, the sensitivity, specificity, and concordance rate of ARMS
      assay were 58.6%, 96.0%, and 65.4%, respectively; and those in ddPCR assay were
      79.3%, 100%, and 83.1%, respectively; the coincidence rate was 83.1%
      (Kappa=0.685, P<0.001). Kaplan-Meier survival analysis showed that patients with
      EGFR gene mutation detected by both ddPCR and ARMS methods had shortest PFS when
      compared with those in patients detected positive with a single method of ddPCR
      or ARMS assay (11.6 moths vs 14.8 months, chi(2)=2.517, P=0.026). Conclusions:
      ddPCR is a reliable technology with high sensitivity and high specificity to
      detect EGFR gene mutations in plasma ctDNA in patients with advanced pulmonary
      adenocarcinoma. Plasma EGFR gene mutation may predict the efficacy of EGFR-TKI
      drugs.

PMID- 30107693
TI  - [Imaging diagnosis of brucella spondylitis and tuberculous spondylitis].
AB  - Objective: To compare the characteristics of X-ray, CT and MRI of Brucella
      spondylitis and tuberculous spondylitis and its significance for differential
      diagnosis. Methods: A total of 10 cases of Brucella spondylitis and 20 cases of
      tuberculous spondylitis confirmed from the clinical, laboratory or pathological
      department were enrolled between January 2014 and August 2017 in the Fifth
      Affiliated Hospital of Sun Yat-sen University and the Third Affiliated Hospital
      of Southern Medical University. The CT, MRI findings were retrospectively
      analyzed to improve the differential diagnosis of these two diseases. Results: Of
      the 10 cases of Brucella spondylitis, 8 were located only in the lumbosacral
      vertebrae, 1 in the thoracic vertebrae only, 1 in the cervical and thoracic
      vertebrae, 8 with invasive bone destruction, and 8 with narrowed intervertebral
      space. In 9 cases of intervertebral disc destruction, 7 cases developed
      paravertebral abscesses, 3 cases had sclerotic edges, all cases had no vertebral
      body flattening, 5 cases invaded the accessory, 4 cases formed sequestrum, and 6
      cases invaded the spinal canal. There were 3 cases showing invasion of
      surrounding muscles. In 20 cases of tuberculous spondylitis, 12 cases were
      located in the lumbosacral vertebrae, 6 cases in the thoracic vertebrae only, 1
      involved the thoracic vertebrae and lumbosacral vertebrae, 1 involved the neck,
      chest, and lumbosacral vertebrae. Bone destruction of bone, 19 cases of
      intervertebral space narrowing, 20 cases of intervertebral disc destruction, 18
      cases of paraspinal abscess formation, 10 cases of sclerotic edge formation, 6
      cases of vertebral body flattened, 16 cases of invading attachment. There were 17
      cases of sequestrum formation, 13 cases of invasion of the spinal canal, and 12
      cases of violation of surrounding muscles. There were statistical differences
      between the two types of imaging signs such as the type of vertebral destruction
      and the presence or absence of sequestrum. Conclusion: The type of vertebral
      destruction and the presence or absence of imaging features such as
      sequestrumwill facilitate the differential diagnosis of Brucella spondylitis and
      tuberculous spondylitis.

PMID- 30107694
TI  - [Future trends and prospect of surgery of gastrointestinal cancer in China].
AB  - With the development of medical concepts and technology, the surgical treatment
      of gastrointestinal cancer is gradually moving towards a new era. Chinese
      gastrointestinal surgeons are building up our own high-level evidence in evidence
      based medicine, with tremendous clinical trials carrying out in gastrointestinal
      cancers. Besides, standardized procedure of diagnosis and treatment should be
      promoted. More personalized schemes are needed. The model of multidisciplinary
      team can be more widely and deeply applied. And the concept of enhanced recovery
      after surgery should be more operable. To keep pace with the times, the
      gastrointestinal surgeons have to seek for innovative technology and new ideas.

PMID- 30107696
TI  - [Treatment for peritoneal metastasis of colorectal cancer].
AB  - Peritoneal metastasis is the second leading cause of death of colorectal cancer
      patients. Cytoreductive surgery (CRS) combined with hyperthermia intraperitoneal
      chemotherapy (HIPEC) is the primary method to treat peritoneal metastasis of
      colorectal cancer, though there remain some controversies. We reviewed current
      studies of colorectal peritoneal carcinomatosis (PC) and CRS+ HIPEC, and
      discussed some issues with regard to the scoring system for peritoneal
      metastasis, selection criteria for CRS+ HIPEC treatment, and the new drug
      application for colorectal PC. Peritoneal carcinomatosis index (PCI) is the most
      useful scoring system for peritoneal metastasis and CRS+ HIPEC is the primary
      treatment for colorectal PC. Patients with PCI<20 should receive thorough
      assessment on the feasibility of R0 or R1 resection and CRS+ HIPEC treatment. For
      patients with unresectable PC at the initial stage, active drug therapy should be
      adopted to achieve tumor regression, so that some of them would have the
      opportunity to receive CRS+ HIPEC treatment.

PMID- 30107695
TI  - [The present situation and future development for robotic gastrointestinal
      surgery in China].
AB  - After ten years of development in robotic gastrointestinal surgery in China,
      although the number of robot surgical systems is small, the growth rate of
      robotic gastrointestinal surgery has grown up. Robotic gastrointestinal surgeons
      used the advantage of robots to perform a variety of surgical procedures with
      high complexity and technical difficulty, and achieved satisfactory clinical
      results. The robotic gastrointestinal surgeons in China are also paying attention
      to clinical research while carrying out robotic surgery. The number of
      international publications on robotic gastrointestinal surgery is at the
      forefront. However, the development of a robotic surgical system with independent
      intellectual property rights, and the further standardization of robotic
      gastrointestinal surgery indications and operational procedures are issues that
      urgently need to be addressed.

PMID- 30107697
TI  - [Optimizing the laparoscopic steps in right colectomy with complete mesocolic
      excision to reduce the intraoperative vascular injuries].
AB  - Laparoscopic right colectomy by the rule of complete mesocolic excision is
      becoming a standard operation for right colon cancer. Intraoperative iatrogenic
      vascular injuries are rare but disastrous complications. In addition to the
      dissection along the embryonic plane, reducing iatrogenic bleeding is of crucial
      importance to safeguard the surgical procedure. Keeping the operative field clear
      by gentle suction to have a good exposure is essential to identify the origin of
      bleeding, and then to make decision how to control the bleeding by bipolar
      coagulation, clipping and transection, suturing or conversion to open surgery.
      For small bleeding, the grasping forceps with bipolar coagulation or clipping
      would usually be effective. When there is laceration locating on the stem of
      superior mesenteric vein or Henle trunk, suturing with 4-0 or 5-0 prolene
      monofilament is suggested. Self-saphenous graft or bridge is advised for stem
      stricture after suturing. The ileocolic vessels are most anatomically constant,
      but with a different relationship between the artery and the vein. The
      tributaries to form the Henle trunk vary quite often, and they usually have close
      relation to the middle colic vein. Right colic artery rarely arises from the
      superior mesenteric artery, and the right colic vein seldom drains into the
      superior mesenteric vein. Anatomical variations are commonly observed in the
      pancreaticoduodenal area, where bleeding happens frequently. Selecting an optimal
      laparoscopic approach and dissecting order, awareness of vascular variation, and
      understanding the anatomical configuration of superior mesenteric vessels and
      their tributaries are important to minimize the intraoperative iatrogenic
      injuries during the meticulous dissections.

PMID- 30107698
TI  - [The current review and prospects of the genetic study and clinical treatment of
      adolescent idiopathic scoliosis].
AB  - This review mainly focused on the etiology and the surgical strategy for
      adolescent idiopathic scoliosis (AIS) treatment. Genome-wide association study on
      the etiology of AIS using samples from more than 5 000 patients and 6 000 normal
      controls showed two genes: LBX1-AS1 on 10q24.32 and TNIK on 3q26.2 highly related
      to AIS initiation and progression. Regarding the conservative treatment of AIS,
      bracing is the only well-documented effective non-operative management in the
      early stage of AIS. For the patients with Cobb angle smaller than 80 degrees ,
      balancing spine, saving fusion level and restoring thoracic kyphosis are the
      basic objectives in surgical management. For the severe cases, various osteotomy
      techniques are often needed. Adequate peri-operative management is important for
      severe cases, especially for the patients with respiratory failure and
      neurological deficits.

PMID- 30107699
TI  - [Evaluation and future direction of three-dimensional laparoscopy in gastric
      cancer].
AB  - It has been thirty years since the three-dimensional (3D) laparoscopy was put
      into clinical use. The advantages of 3D laparoscopy are depth perception, high
      cost-efficacy, tactile feedback, education for basic procedures in laparoscopy
      and accurate operation. Currently, high-level of evidence for 3D laparoscopy in
      gastric cancer is still lacking. The advantage of 3D laparoscopy could be
      maximized in complicated procedures, like hilar lymphadenectomy and totally
      laparoscopic reconstruction in gastrectomy. In order to acquire optimal depth
      perception, optimal standing position and stereoacuity check should be emphasized
      for surgeons in 3D laparoscopic surgery. In light of the limitation of 3D
      laparoscopy, glass-free 3D laparoscopy and real-time navigation-assisted 3D
      laparoscopy may be one of the future directions. The value of 3D laparoscopy in
      obese patients and comparison with robot surgical system are worth further
      investigating.

PMID- 30107700
TI  - [Emphasis on standardization of follow-up after gastrectomy].
AB  - The high postoperative recurrence rate of advanced-stage gastric cancer has been
      an unsolved problem for its treatment. Postoperative surveillance is an important
      step for the multiple disciplinary treatment. At present, most guidelines
      worldwide recommended standardization programs of follow-up after gastrectomy,
      based on different timing and items. Standard postoperative surveillance is
      critical for the building up of multiple disciplinary team. And to make sure the
      success of postoperative surveillance, we should specify the timing and items
      according to different recurrence risks by prediction model. In the end,
      improving the quality of postoperative surveillance is the key to benefit
      patients of gastric cancer.

PMID- 30107702
TI  - [Establishment of multiple predictor models of severe acute pancreatitis in
      elderly patients].
AB  - Objective: To investigate the prognostic factors related to the severity of acute
      pancreatitis and to establish the multiple predictor models of severe acute
      pancreatitis(SAP) in elderly patients. Methods: Clinical data of 146 consecutive
      elderly patients who met the inclusion criteria between January 2014 and May 2017
      at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of
      Harbin Medical University were retrospectively collected and analyzed, wherein 88
      cases were mild acute pancreatitis, 29 cases were moderately severe acute
      pancreatitis and 29 cases were SAP. The patients data were subjected to
      univariate analysis and multiple classified Logistic regression analysis for
      independent prognostic factors of the severity of acute pancreatitis in elderly
      patients. Unweighted predictive score(unwScore) and weighted predictive
      score(wScore)for SAP in elderly patients were established according which the
      receiver-operating characteristic(ROC) curves of independent prognostic factors
      and predictor models were produced. The cutoff values of independeut prognostic
      factors and predictor models were determined. The area under the curve, the
      sensitivity, the specificity, the positive predictive value and the negative
      predictive value to verify the predictive efficiency of the independent
      prognostic factors and predictor models were calculated. Results:
      Procalcitonin(PCT)(Z=10.564, P=0.000), blood urea nitrogen(BUN)(Z=22.231,
      P=0.003), serum creatinine(Scr)(Z=14.151, P=0.030), serum calcium(Z=34.979,
      P=0.032) and pleural effusion(chi(2)=28.463, P=0.015) were independent prognostic
      factors of the severity of acute pancreatitis by univariate analysis and multiple
      classified Logistic regression analysis in elderly patients. Respectively, the
      area under the curve of PCT, BUN, Scr, serum calcium and pleural effusion were
      0.908, 0.737, 0.701, 0.753, 0.712, the sensitivity were 0.828, 0.621, 0.552,
      0.690, 0.517, the specificity were 0.915, 0.786, 0.846, 0.966, 0.906, the
      positive predictive value were 70.6%, 41.9%, 47.1%, 83.3%, 57.7%, the negative
      predictive value were 95.5%, 89.3%, 88.4%, 92.6%, 88.3%. Respectively, the area
      under the curve of unwScore and wScore were 0.915 and 0.953, the sensitivity were
      0.759 and 0.931, the specificity were 0.889 and 0.915, the positive predictive
      value were 62.9% and 73.0%, the negative predictive value were 93.7% and 98.2%.
      Conclusions: PCT, BUN, Scr, serum calcium and pleural effusion were independent
      prognostic factors of the severity of acute pancreatitis in elderly patients. The
      multiple predictor models of SAP in elderly patients have a good predictive
      efficiency, which may provide valuable clinical reference for prediction and
      treatment.

PMID- 30107701
TI  - [Diagnosis and treatment experience of 161 cases of pancreatic serous cystic
      neoplasm in single center and analysis of cause of preoperation misjudgement].
AB  - Objective: To analyze the causes of preoperative miscarriage of pancreatic serous
      cystadenoma (SCN) and find the ways to improve it. Methods: Clinical data of 425
      pancreatic cystic neoplasm patients who underwent surgical resection from January
      2006 to December 2016 in Department of Pancreatic Surgery in Huashan Hospital
      were retrospectively analyzed.Excel database was created which covered 128 fields
      of 7 fields: general information of patients, preoperative blood biochemical
      indexes, tumor markers, surgical related data, postoperative complications,
      imaging findings and pathology.One hundred and sixty-one cases of SCN were
      analyzed in depth, mainly in three aspects: surgical benefit, preoperative
      imaging diagnostic value and interference factors in preoperative judgement.The
      classification data were analyzed by chi(2) test and the quantitative data were
      analyzed by t test.The Logistic regression model was used for multiple factor
      analysis. Results: Of the 425 PCN cases surgically removed, 161 cases (37.9%)
      were SCN, the incidence of operative complications was 40.4%(65/161), the
      hospitalization days was (20.7+/-12.1)days and the medical cost was (75 267+/-37
      866) yuan.Only 3 of 161 cases of SCN were accurately diagnosed by preoperative
      imaging methods, 61 cases were diagnosed as "cystic lesions of pancreas" (37.9%)
      and 52 cases were diagnosed as "pancreatic cystadenoma" (32.3%). SCN was
      misdiagnosed as MCN(32.3%) and IPMN(28%) before operation.25.5% of them were
      diagnosed as SCN before operation, but still underwent radical operation.The rate
      of preoperative imaging diagnosis for identifying SCN was 62.8%.The lack of
      preoperative endoscopy and the lack of understanding of the image characteristics
      and biological behavior of SCN were the most important factors affecting the
      accuracy of preoperative judgment.Statistics found that gender, age, CA125 and
      tumor location can be used as independent factors contribute to the clinical
      identification(chi(2)=8.995, P=0.003; chi(2)=10.019, P=0.007; t=3.157, P=0.002;
      chi(2)=6.790, P=0.009). Logistic analysis showed that women, older than 60 years
      old, the tumors located in the pancreatic body and tail were the independent
      factors of SCN classification and diagnosis (OR=0.481, 0.376, 0.577, 0.666, 95%
      CI: 0.305-0.759, 0.199-0.710, 0.361-0.924, 0.433-1.024, P=0.002, 0.003, 0.022,
      0.064). Conclusions: SCN has more benign biological behavior.Although surgical
      excision is acceptable for clinical safety, the corresponding benefit is very
      limited.It is possible to improve the rationality of SCN clinical operation
      decisions to some extent by performing endoscopic examination, imaging doctors to
      improve the SCN feature recognition and surgeons to enhance the awareness of SCN.

PMID- 30107703
TI  - [The application of intestinal stomas in mesenteric ischemia].
AB  - Objective: To evaluate the application of intestinal stomas in mesenteric
      ischemia (MI) according to the concept of damage control surgery. Methods:
      Clinical data of 59 MI patients received intestinal stomas at Jinling Hospital,
      Nanjing University School of Medicine from January 2010 to June 2017 were
      analyzed retrospectively. There were 41 male and 18 female patients aging of
      (51+/-14) years (ranging from 20 to 86 years). All the patients were divided to
      two groups according to the degree of bowel ischemia: acute MI group (AMI, bowel
      necrosis, n=43) and chronic MI group (CMI, bowel stricture, n=16). The medium
      time from onset to consult of AMI was 7(12) days (M(Q(R))) and the time of CMI
      was 80(51) days. After the resection of irreversible ischemic intestine, ostomy
      was carried out for all 59 patients. Patients received oral anticoagulation,
      enteral nutrition and succus entericus reinfusion therapy for about 6 months
      after discharge. Then definite surgery to restore digestive tract was preferred.
      Results: In AMI group, APACHEII score in admission was (16+/-3). The length of
      infarcted intestine resected was (160+/-95) cm, normal bowel left was (220+/-106)
      cm. Twelve patients had complications during first post-operation period
      including sepsis (n=8), acute renal failure (n=4), acute respiratory distress
      syndrome (n=4), short bowel syndrome (n=4). 30-day mortality was 18.6%. Total 30
      patients received operation to restore the continuity of intestinal tract after
      202(42) days and APACHEII score was 4+/-2. Two patients suffered from sepsis and
      were cured after anti-infection. In CMI group, APACHEII score was 16+/-3 and
      NRS2002 score was more than 3. The length of infarcted intestine resected was
      (43+/-33) cm. All patients had restored the continuity of intestinal tract after
      176 (47) days. No major complications occurred during the first and second post
      operation period. Conclusions: According to damage control surgery, after early
      revascularization, patients with acute intestinal necrosis should be treated with
      infarcted bowel resection and stomas. Besides, second operation to restore the
      continuity of intestinal tract should be conducted after nutritional support for
      6 months. Patients with ischemic enteropathy who cannot be corrected with severe
      malnutrition should achieve stomas during first operation.

PMID- 30107704
TI  - [A retrospective comparative study of continuous pumping for home enteral
      nutrition after esophagectomy].
AB  - Objective: To discuss the effect and safety of continuous pumping for home
      enteral nutrition after esophagectomy. Methods: The current study retrospectively
      analyzed the esophageal cancer patients who underwent transthoracic esophagectomy
      between January 2017 and November 2017 at First Department of Thoracic Surgery,
      Peking University Cancer Hospital and Institute. There were totally 108 cases,
      including 88 males and 20 females, with an average age of 62 years. The patients
      were divided into pump feeding group (n=56) and traditional tube feeding group
      (n=52). The postoperative short-term safety, weight maintenance, enteral
      nutrition tolerance and nutritional support complete rate of the 2 groups were
      compared by chi(2) test, Fisher exact test and t test, respectively. Results:
      Compared with traditional tube feeding group, the patient safety in pumping
      feeding group was significantly better, with complications within 2 months after
      discharge were 11/52 and 4/56 respectively (chi(2)=2.393, P=0.035); the weight
      maintenance was significantly better, the weight loss within 4 weeks after
      discharge were 3.90 kg and 0.13 kg, respectively (t=7.720, P=0.000); the general
      enteral complications were significantly lower (26/52 vs. 5/56, chi(2)=22.225,
      P=0.000), the nutritional support complete rate was significantly higher (23/52
      vs. 55/56, chi(2)=39.167, P=0.000). Conclusions: Continuous pump feeding enteral
      nutrition support after discharge postoperatively could help improve patient
      safety after discharge, which is better for weight maintenance of the patients.
      Pump feeding could also enhance tolerability of tube feeding and ensure the
      effective accomplishment of nutritional support.

PMID- 30107705
TI  - [The sodium fluorescein-guided microsurgical resection of glioblastoma].
AB  - Objective: To investigate the clinic effect of the sodium fluorescein-guided
      microsurgical resection of glioblastoma. Methods: In a retrospective clinical
      study, 82 patients with glioblastoma confirmed by post-operative pathologic
      inspection in the Department of Neurosurgery of Tianjin Huanhu Hospital from
      January 2016 to June 2017 were randomly divided into sodium fluorescein (FL)
      group (42 cases) and traditional microsurgical (TM) group (40 cases). The tumors
      were removed by the sodium fluorescein-guided surgical procedure in the FL group.
      The tissues which displayed different intensity of fluorescent staining were
      taken for the pathologic inspection. The resection of tumors were completed under
      common microscope in the TM group. The two groups of patients underwent MRI
      enhanced scan at 48 hours after operation to determine the degree of tumor
      resection. The rate of gross total resection, postoperative complication,
      recurrent rate of two groups were compared by chi(2) test or Fisher exact test.
      Results: Totally 135 fluorescent staining samples were obtained in the FL group.
      Forty-two samples were showed strong fluorescent staining, and all samples were
      proved to be tumor tissue by pathologic inspection, the sensitivity of FL was
      100%. Thirty-seven gliomas were detected from 45 samples of faintly fluorescent
      staining, sensitivity of FL was 82.3%. Eight gliomas were found from 48 samples
      of non-fluorescent staining, the specificity of FL was 83.3%. The total resection
      rate of sodium fluorescein group was 85.7% (36/42), higher than that of
      traditional microsurgical group (62.5% (25/40)) (chi(2)=5.795, P=0.016). Two
      groups of patients were followed up to 6 months after the operation, and 6 cases
      (14.3%, 6/42) were recurred in the FL group. Among them, 1 case died and the
      average Karnofsky performance score was 82.2+/-15.2. There were 12 recurrent
      cases (33.3%, 12/36) in the TM group, of which 2 cases were died and the average
      Karnofsky performance score was 76.9+/-20.3. There was significantly statistical
      difference in recurrent rate (chi(2)=3.962, P=0.047). Conclusions: The
      sensitivity and specificity of fluorescein staining in glioblastoma tissue are
      high. And the application of sodium fluorescein-guided microsurgical resection of
      glioblastoma is safe and simple. Therefore, it is helpful to improve the total
      resection rate of glioblastoma patients and reduce the recurrence rate.

PMID- 30107706
TI  - [Kindlin-2 promotes gallbladder cancer metastasis and invasion by inducing
      epithelial-mesenchymal transition].
AB  - Objective: To investigate the effects of Kindlin-2 on malignant phenotypes of
      human gallbladder cancer cells and discuss the mechanisms. Methods: The
      expression level of Kindlin-2 in 30 cases of gallbladder cancer tissues and
      adjacent non-tumoral tissues collected from the First Affiliated Hospital of
      Zhengzhou University between September 2012 and May 2013 was assessed by real
      time PCR and immunohistochemistry.Lentivirus-mediated Kindlin-2 overexpression
      was used in gallbladder cancer cell lines GBC-SD and SGC-996.Transwell assay and
      adhesion assay were investigated to explore the functional role of Kindlin-2 on
      gallbladder cancer cells.Western Blot was used to test the protein change of
      epithelial-mesenchymal transition(EMT) characteristics. The t-test was used to
      analyzed results. Results: The RNA and protein levels of Kindlin-2 in gallbladder
      cancer tissues were higher than in the non-tumoral tissues (t=4.372, P=0.001;
      t=7.477, P=0.000). The expression level of Kindlin-2 in gallbladder cancer
      tissues was correlated with Nevin stage(chi(2)=5.932, P=0.035). Compared with
      control groups, the cell-matrix adhesion ability of GBC-SD and SGC-996 with
      Kindlin-2 overexpression was obviously promoted(1.66+/-0.03 vs. 1.07+/-0.22,
      t=2.710, P=0.041; 2.66+/-0.24 vs. 1.03+/-0.02, t=6.610, P=0.020). The number of
      GBC-SD and SGC-996 cells with Kindlin-2 overexpression passing through the
      Transwell chamber matrix increased significantly compared with the control
      groups(116.1+/-13.9 vs. 54.7+/-8.4, t=3.781, P=0.019; 136.3+/-7.5 vs. 64.3+/-6.4,
      t=7.302, P=0.002). The wound healing rate of GBC-SD with Kindlin-2 overexpression
      at 12-hour and 24-hour was higher than that of the group ((42.9+/-2.2)% vs.
      (29.7+/-1.7)%, t=4.690, P=0.009; (65.0+/-2.4)% vs.(40.4+/-2.0)%, t=7.945,
      P=0.001). The wound healing rate of SGC-996 with Kindlin-2 overexpression at 12
      hour and 24-hour was also higher than that of the group ((32.9+/-1.3)% vs.
      (24.1+/-1.5)%, t=4.518, P=0.011; (51.3+/-1.1)% vs. (39.2+/-1.1)%, t=8.001,
      P=0.001). The characteristics of EMT were induced in gallbladder cancer cells
      with Kindlin-2 overexpression, including the up-regulation of N-cadherin,
      Vemintin and the down-regulation of E-cadherin. Conclusion: The expression of
      Kindlin-2 is up-regulated in gallbladder cancer tissues and Kindlin-2 promoted
      the malignant phenotypes of gallbladder cancer cells partially by epithelial
      mesenchymal transition.

PMID- 30107707
TI  - [Research progress on the clinical significance of sagittal alignment and balance
      in cervical spine].
AB  - Though great progress on spinal sagittal alignment has been seen recently, which
      focuses on the lumbar spine-pelvic region and the whole spine, while there is a
      few research mainly concentrated on the cervical spine. In recent years, a
      growing number of researchers have been exploring the changes in the compensation
      of cervical sagittal alignment and their effect on surgery, and the preliminary
      results of these researches are satisfactory. The present review focuses on the
      measurement of sagittal plane parameters of cervical spine, changes of sagittal
      alignment in cervical spine disorders, and its effect on cervical surgery.

PMID- 30107708
TI  - [Pay attention to adolescent health and build solid foundation for healthy
      China].

PMID- 30107709
TI  - [Introduction to World Health Organization Guidelines on Protecting Workers from
      Potential Risks of Manufactured Nanomaterials].

PMID- 30107710
TI  - [Association of the health literacy and the incidence of injuries among Chinese
      middle school students in five provinces].
AB  - Objective: The purpose of this study was to examine the association between
      health literacy (HL) and the incidence of injuries in middle school students in
      China. Methods: From November 2013 to February 2014, middle school students in
      Liaoning, Henan, and Guangdong provinces, Chongqing municipality, Xinjiang Uygur
      Autonomous Region were selected by using cluster sampling method. A total of 27
      044 questionnaires were issued and 25 378 questionnaires were valid. According to
      the Chinese Adolescent Interactive Health Literacy Questionnaire (CAIHLQ), scores
      were conducted a tripartite group. Multiple logistic regression analyses were
      conducted to examine the association between HL and injuries. Results: The scores
      of CAIHLQ were 103.55+/-23.91 among 25 378 students. The detection rate of self
      injuries and unintentional injuries was 27.5% (n=6 971) and 47.8% (n=12 119).
      Compared with the students with high HL, the OR (95%CI) values of self-injuries
      among students with low and middle HL were 2.56 (2.35-2.79) and 1.96 (1.81-2.12).
      Compared with the students with high HL, the OR (95%CI) values of unintentional
      injuries among students with low and middle HL were 1.63 (1.53-1.73) and 1.47
      (1.37-1.58). Conclusion: The risk of self-injuries and unintentional injuries of
      middle school students is related to HL.

PMID- 30107711
TI  - [The association between the malnutrition and blood pressure in Chinese Han
      students aged 7-18 years in 2014].
AB  - Objective: This study aimed to explore the association between malnutrition and
      the level of blood pressure (BP) as well as elevated BP (EBP) in Han students
      aged 7 to 18 years in China. Methods: 170 037 subjects with normal nutritional
      status and malnutrition were enrolled in this study from 2014 Chinese National
      Surveys on Students' Constitution and Health with a multi-stage stratified
      cluster random sampling framework covering 31 provinces, autonomous regions and
      municipalities after the exclusion of 44 317 overweight and obese students.
      According to the standard of "Screening Standard for Malnutrition of School-age
      Children and Adolescents" (WS/T456-2014), the nutritional status of children were
      classified into two categories, normal nutritional status and malnutrition
      containing stunting, mild wasting and moderate severe wasting. The level of BP
      and prevalence of EBP were compared between students with normal nutritional
      status and malnutrition. The multivariate logistic regression model was used to
      analyze the association between malnutrition and EBP. Results: The levels of
      systolic BP (SBP) and diastolic BP (DBP) in Chinese Han students aged 7-18 years
      who were non-overweight and non-obesity status were (103.4+/-12.3) and (64.7+/
      9.5) mmHg (1 mmHg=0.133 kPa), respectively. The prevalence of EBP, systolic EBP
      and diastolic EBP in Chinese Han malnourished students (N=21 012) were 3.1%
      (n=649), 1.5% (n=324) and 2.1% (n=445), respectively, which was significantly
      lower than those (N=148 320) with normal nutritional status (4.5% (n=6 707), 2.6%
      (n=3 872) and 2.7% (n=3 959)), and the corresponding differences were
      statistically significant (P<0.05). The OR (95%CI) between malnutrition and EBP
      was 0.68 (0.62-0.73), which were 0.65 (0.58-0.72) and 0.68 (0.60-0.77) for boys
      and girls. The OR (95%CI) between EBP and stunting as well as mild wasting and
      moderate severe wasting were 0.69 (0.62-0.77), 0.63 (0.55-0.72) and 0.79 (0.60
      1.05), respectively. Conclusion: The level of BP and prevalence of EBP in Chinese
      Han students with malnutrition were lower than those with normal nutritional
      status. The negative correlation existed between malnutrition and EBP in Chinese
      Han students aged 7 to 18 years.

PMID- 30107712
TI  - [The epidemiological characteristics and related factors of dyslipidemia among
      children and adolescents aged 6-17 years from 7 provinces in China, 2012].
AB  - Objective: To investigate the prevalence and related factors of dyslipidemia
      among children and adolescents aged 6-17 years in 7 provinces in China. Methods:
      Using the method of stratified cluster random sampling, 93 primary and secondary
      schools were selected from Guangdong, Hunan, Liaoning provinces, Shanghai,
      Chongqing, Tianjin municipalities and Ningxia Hui Autonomous Region in China,
      2012. A total of 16 434 students aged 6-17 years old with completed physical and
      lipid profiles parameters were selected into this study from above 93 primary and
      secondary schools. Dyslipidemia was determined by the definition of Expert Advice
      on Prevention and Treatment of Dyslipidemia in Children and Adolescents in 2009.
      Logistic regression model was used to explore the factors related to
      dyslipidemia. Results: The prevalence of elevated total cholesterol, elevated
      triglyceride, elevated low-density lipoprotein cholesterol, low high-density
      lipoprotein cholesterol, and dyslipidemia was 5.4% (887 cases), 15.7% (2 578
      cases), 3.0% (492 cases), 13.5% (2 221 cases) and 28.5% (4 679 cases) among
      children and adolescents aged 6-17 years, respectively. Sugary drinks intake
      >=once per week (OR=1.14; 95%CI: 1.05-1.24), sedentary time >10 hours per day
      (OR=1.14, 95%CI: 1.01-1.28), overweight (OR=1.50, 95%CI: 1.33-1.70), and obesity
      (OR=2.62, 95%CI: 2.31-2.96) were significantly associated with the prevalence of
      dyslipidemia. Conclusion: The prevalence of dyslipidemia was high among children
      and adolescents aged 6-17 in 7 provinces in China, 2012. Sugary drinks intake
      >=once per week, sedentary time >10 hours per day, overweight and obesity might
      be the risk factors of dyslipidemia among children and adolescents.

PMID- 30107713
TI  - [The change in mortality and major causes of death among Chinese adolescents from
      1990 to 2016].
AB  - Objective: To analyze the change in mortality and major causes of death among
      Chinese adolescents aged 10-19 years from 1990 to 2016. Methods: Data of death
      for Chinese adolescents aged 10-19 years were extracted from the Global Burden of
      Disease Study 2016 (GBD 2016). The data was used to describe the change in
      mortality of Chinese adolescents from 1990 to 2016.Top 15 causes of death were
      compared between 1990 and 2016. Results: From 1990 to 2016, the all-cause
      mortality of Chinese adolescents aged 10-19 years old dropped from 102.5/100 000
      to 41.2/100 000, reaching about a half of the global average (78.6/100 000) but
      still almost twice as high as the average of high-income countries (24.3/100 000)
      by 2016; the reduction in mortality was higher among females than that among
      males (decreased 68.7% vs. 54.7%), and among adolescents aged 10-14 years than
      that among those aged 15-19 years (decreased 62.1% vs. 57.1%). During the 26-year
      period, the cause-specific mortality of all top 15 causes saw sharp decreases.
      Among them, communicable, maternal, and nutritional diseases saw the most
      significant decrease (78.1%), and its proportion in all adolescent deaths fell
      from 11.1% to 6.1%. Meanwhile, non-communicable diseases and injuries saw
      relatively small decreases (58.2% and 57.3% respectively), and their proportions
      rose from 33.4% and 55.6% to 34.8% and 59.1%, respectively. The top 5 causes of
      death changed from drowning (17.39/100 000 in mortality, 17.0% in proportion),
      road injuries (14.77/100 000, 14.4%), self-harm (11.44/100 000, 11.2%), leukemia
      (5.48/100 000, 5.4%) and interpersonal violence (3.12/100 000, 3.0%) in1990 into
      road injuries (9.27/100 000, 22.5%), drowning (6.83/100 000, 16.6%),
      leukemia(2.73/100 000, 6.6%), self-harm (2.53/100 000, 6.2%) and congenital birth
      defects (1.76/100 000, 4.3%) in 2016, and tuberculosis, poisonings and rheumatic
      heart disease had dropped out of the top 15 in 2016. Conclusion: The mortality of
      Chinese adolescents aged 10-19 years has decreased significantly, but still
      higher than developed countries. Since 1990, injuries,especially for road
      injuries and drowning, have always been the leading causes of death among Chinese
      adolescents aged 10-19 years, followed by non-communicable diseases.

PMID- 30107714
TI  - [Analysis on prevalence of physical fitness and related influencing factors among
      Chinese Han students aged 13-18 years in 2014].
AB  - Objective: To analyze the prevalence of physical fitness among Chinese Han
      students aged 13-18 years in 2014, and explore related influencing factors.
      Methods: This study recruited 106 881 Han students aged 13-18 years who had taken
      physical fitness test from Chinese National Survey on Students' Constitution and
      Health in 2014. After the exclusion of 1 047 students without complete records of
      physical fitness test, 105 834 students were included in the final analysis.
      According to the National Student Physical Health Standard modified in 2014,
      seven indicators including body mass index, vital capacity, 50-m run, sit-and
      reach, standing broad jump, pull-ups/curl-ups and endurance run were tested to
      calculate the total score of students' physical fitness. Students with score >=60
      were regarded as qualified students. Multivariate non-conditional logistic
      regression model was used to analyze influencing factors of physical fitness.
      Results: Among Chinese Han students aged 13-18 years, the total score was 70.1+/
      10.7 and the qualified rate was 83.9% (n=88 813). Boys (83.5% (44 197/52 910))
      had a lower qualified rate of physical fitness than girls (84.3% (44 616/52 924))
      (P<0.001), and 13-15 age group (86.5% (46 255/53 465)) was higher than the 16-18
      age group (81.3% (42 558/52 369)) (P<0.001). Except for 16-18-year-old boys from
      central region, normal body mass index, eastern region, good socioeconomic
      status, enough PE class, exercise time >=1 h/d, homework time >=2 h/d, TV time <1
      h/d were all related to high qualified rates of physical fitness (P<0.05).
      Conclusion: Chinese Han students aged 13-18 years were in good physical
      condition. The qualified rates of physical fitness were significantly different
      by gender and age groups. Nutritional status, region, socioeconomic status, PE
      class, exercise time per day, homework time per day, and TV time per day were
      related factors of physical fitness.

PMID- 30107715
TI  - [A nested case-control study of cruciferous vegetables intake, urinary
      isothiocyanates level and lung cancer risk among men in urban Shanghai].
AB  - Objective: To investigate the association between consumption of cruciferous
      vegetables (CV), level of urinary isothiocyanates (ITC) and the risk of lung
      cancer among man in urban Shanghai. Methods: A nested case-control study was
      conducted within the Shanghai Men's Health Study. Using incidence density
      sampling with a 2?1 control to case selection ratio, 885 controls were selected
      to match 443 lung cancer cases diagnosed prior December 31, 2010. A food
      frequency questionnaire was administered to estimate CV consumption. The high
      performance liquid chromatography method was applied to measure urinary ITC
      level. The CV intake and urinary ITC level were divided into quartiles according
      to distribution of control group. The lowest quartile was as a reference group.
      Conditional logistic regression model was used to analyze the relationship
      between CV intake, urinary ITC level and the risk of lung cancer. Results: The
      cruciferous vegetables intake median (P(25), P(75)) in cases and controls were
      80.05 (46.89, 129.04) and 97.68 (55.25, 151.72) g/d (Z=-3.93, P<0.001). The
      urinary ITC level were 1.256 (0.474, 3.836) and 1.244 (0.484, 3.004) MUmol/g Cr
      (Z=-0.39, P=0.697). After adjusting for potential confounding factors such as
      age, education level, smoking and alcohol consumption, for urinary ITC level, the
      OR(95%CI) for the highest quartile(>=3.004 MUmol/g Cr) was 1.25 (0.87-1.80)
      compared with the lowest quartile(<0.484 MUmol/g). For CV intake, the OR(95%CI)
      for the highest quartile(>=151.71 g/d) was 0.66 (0.43-1.02) compared with the
      lowest quartile(<55.25 g/d). Conclusion: No association was found between the CV
      intake, urinary ITC level and lung cancer risk in men.

PMID- 30107716
TI  - [A promoter polymorphism of CD55 effect on the risk of esophageal cancer].
AB  - Objective: This study aimed to investigate the relationship between the genetic
      variation of CD55 promoter and the risk of esophageal cancer. Methods: A total of
      700 esophageal cancer patients recruited between April 2008 and December 2012 at
      Tangshan Grongren Hospital and Tangshan Renmin Hospital, and 700 frequency
      matched controls were randomly selected from a pool of cancer free subjects
      recruited from a nutritional survey. Genotypes of CD55 rs2564978 polymorphism
      among all subjects were conducted by polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP). The OR and 95%CI were calculated by non
      conditional Logistic regression to evaluate the association of CD55 rs2564978T/C
      polymorphism with the risk of esophageal cancer. Results: The average age of
      cases and control was (60.04+/-9.19) and (59.21+/-9.98) years old. Compared with
      CD55 rs2564978 TT carriers, the individuals with CC genotype had a significantly
      higher risk of esophageal cancer (OR=1.94, 95%CI:1.42-2.66) . When stratified by
      sex, this genetic variation affected the risk of esophageal cancer among both
      males (OR=1.92, 95%CI:1.37-2.70) and females (OR=2.34, 95%CI:1.04-5.27). When
      stratified by age, the CD55 rs2564978 CC was associated with the susceptibility
      of developing esophageal cancer among younger individuals (OR=1.79, 95%CI:1.19
      2.68) and older people (OR=2.32, 95%CI:1.41-3.83).When stratified by drinking
      status, CC genotype carriers increase the risk of esophageal cancer when drinking
      (OR=1.93, 95%CI:1.03-3.63) or not drinking (OR=1.95, 95%CI:1.36-2.80). When
      stratified by smoking status, CC genotype was associated with the risk of
      esophageal cancer among non-smokers (OR=1.79, 95%CI: 1.13-2.83), light smokers
      (less than 30 packs/year, OR=1.86, 95%CI:1.31-2.64) and heavy smokers (more than
      30 packs/year, OR=2.67, 95%CI:1.28-5.57). Gene-environmental interaction analysis
      showed that CD55 rs2564978T/C polymorphism interacted with smoking status to
      increase the risk of esophageal cancer. Conclusion: CD55 rs2564978 polymorphism
      effects on the risk of esophageal cancer.

PMID- 30107717
TI  - [Association of CYP19A1 gene rs7176005 single nucleotide polymorphism with breast
      cancer risk and clinicopathologic features of tumor].
AB  - Objective: The aim of this study was to investigate the association of the
      CYP19A1 rs7176005 single nucleotide polymorphism (SNP) with breast cancer risk
      and with clinicopathologic features of tumors. Methods: This study was conducted
      by including 138 patients with breast cancer (cancer group), those who diagnosed
      as primary breast cancer after operation by pathology. There were 293 cases in
      the group of benign breast disease which was presented as a solid mass by the
      color ultrasound and pathologically diagnosed as "fibroadenoma or adenosis"
      (benign breast disease group), the cases were paired with breast cancer patients
      by age+/-5 in the same period, and there were 259 cases in the group of healthy
      control who received routine physical examination during the same period and were
      paired with breast cancer patients by age+/-5 without any detection of breast
      related diseases (healthy control group) at West China hospital between September
      2012 and November 2016. The CYP19A1 rs7176005 SNP was detected by a direct
      sequencing method. Hardy-Weinberg test was used to analyze the genetic balance of
      the 3 groups. Chi square test was used to compare the distribution of rs7176005
      genotypes between the 3 groups, and the differences of clinicopathological
      features in breast cancer patients carrying different genotypes. Results: The
      ages of the breast cancer cases, the benign breast disease group and the healthy
      control group were (44.69+/-8.09), (42.33+/-11.44) and (41.92+/-9.61) years old,
      respectively. Hardy-Weinberg equilibrium test identified that the composition
      ratios of alleles C and T in breast cancer group, benign breast disease group and
      healthy group were not statistically significant (chi(2) values were 0.83, 0.34
      and 0.04, respectively, P values were 0.363, 0.561, and 0.852, respectively). All
      the three groups met the genetic balance, had consistency and could represent the
      population. Among the 138 cases of breast cancer, the CYP19A1 rs7176005 SNP was
      significantly associated with the diameter of the tumor (P=0.031). The majority
      of tumor size was <2 cm in patients who carrying TT and CT genotypes, and the
      proportion was 75% (12/16) and 58% (40/69), respectively. While those patients
      with TT genotype were mainly >2 cm and <=5 cm, and the proportion was 51%
      (27/53). The distribution of TNM stage among patients with different genotypes
      was also statistically significant (chi(2)=11.19, P=0.025). The most common stage
      was II in Patients who carrying CC and CT genotypes, and the proportion was 45.3%
      (24/53) and 52.2% (36/69), respectively. While those patients with TT genotype
      was mainly in stage I and the proportion was 56.3% (9/16). Conclusion: Though the
      CYP19A1 rs7176005 SNP is not associated with breast cancer development, breast
      cancer patients with the C allele exhibit a high tumor growth rate and large
      diameters.

PMID- 30107718
TI  - [Estimation of HIV diagnosis rate with CD4(+) T-lymphocyte level and infected
      time model in Dehong Prefecture, Yunnan Province].
AB  - Objective: To estimate the total number of people infected with HIV and to
      calculate the diagnosis rate of HIV in Dehong Prefecture, Yunnan Province.
      Methods: Through the comprehensive AIDS prevention and treatment information
      system, we collected and analyzed the relevant information of the new diagnosis
      report of HIV in Dehong Prefecture, Yunnan Province in 2006-2015, mainly
      including age, sex, infected transmission, CD4(+) T-lymphocyte counts, diagnostic
      time and so on. The content of the study was to establish a model method for
      estimating the diagnosis rate of HIV in Dehong. First, used the first CD4(+) T
      lymphocyte count after HIV diagnosis to estimate the date of infection. Then
      based on the estimated time from HIV infection to diagnosis we can estimate the
      diagnosis delay distribution which in turn can be used to account for individuals
      infected but not yet diagnosed and thus estimated the total number of HIV
      infections (diagnosed and undiagnosed). Finally, the number of new infections in
      each year was added to estimate the total number of infected people, and the
      number of people who had been diagnosed was divided by the total number of
      infected persons to obtain the proportion of HIV diagnosis rate. Results: There
      were 8 215 reported cases in Dehong from 2006 to 2015, of which 1 297 cases were
      reported in 2007 (15. 8%) and 361 cases (4.4%) in 2015. The diagnosis rate of
      newly infected persons were 88% in 2005 and before. And from 2006 to 2015, the
      diagnosis rate of newly infected persons were 75%, 71%, 68%, 66%, 61%, 58%, 53%,
      45%, 40% and 33%, respectively. The total number of newly infected persons in
      2005 and before was 11 197 cases. The annual new infected number from 2006 to
      2015 was 653, 671, 723, 640, 509, 468, 369, 375, 285 and 224 cases. The total
      number of people infected with HIV in Dehong was 16 114 cases, and the diagnosis
      rate was 87.7%. Conclusion: The diagnosis rate of HIV in Dehong was at a high
      level. Since 2008, the annual number of new infections in Dehong has been
      declining.

PMID- 30107719
TI  - [Evaluation of economic outcomes of "hepatitis B vaccine event reported by media"
      in China, 2013].
AB  - Objective: To edentify the increased cost, the decreased benefits and
      effectiveness of hepatitis B vaccine event reported by media in 2013 in China
      both in Chinese nationwide and in Shenzhen. Methods: The decision analytic-Markov
      models were constructed. The cohort born in 2013 in nationwide and in Shenzhen
      were respectively introduced to the models. The vaccination coverage and the
      rates of antibody to hepatitis B surface antigen were determined as major
      parameters. The average costs and benefits per case, the effectiveness which
      included the numbers of hepatitis B virus (HBV) infection and the patients with
      HBV-related diseases, the average quality-adjusted life years (QALYs) per case
      were calculated from the medical-care and societal perspectives. The benefit cost
      ratio (BCR), ratio of the total costs and the net QALYs were as indicators of
      cost-benefit and cost-effectiveness analysis, respictively. Results: In
      nationwide, the BCRs decreased from 9.10 and 8.58 to 2.48 and 2.43, respectively,
      because the average costs increased to 6 796.60 yuan (RMB) and 8 451.45 yuan, and
      average benefits decreased to 6 799.57 yuan and 8 484.41 yuan, respectively, from
      the medical-care and societal perspectives. In Shenzhen, the BCRs decreased from
      16.21 and 14.51 to 3.11 and 3.04 with the average costs of 5 244.88 yuan and 8
      937.64 yuan, and average benefits of 5 248.11 yuan and 8 977.27 yuan. Totally,
      the increase of 2.1314 million and 181 hundreds of the HBV infectors occurred for
      the event in nationwide and in Shenzhen, respectively. Of all the infectors
      increased the most, the numbers of acute and chronic hepatitis B were 1 904
      hundreds and 807 hundreds in nationwide, 794 and 395 in Shenzhen, espectively.
      The decreases of average QALY per case were 0.119 8 in nationwide and 0.090 6 in
      Shenzhen. The costs per averted a QALY increased from 6 231.90 yuan to 22 883.51
      yuan in nationwide, from 3 567.25 yuan to 1 8571.49 yuan in Shenzhen (for medical
      care perspective), from 8 252.79 yuan and 6 807.45 yuan to 29 091.92 yuan and 32
      553.60 yuan (for societal perspective). Conclusion: The hepatitis B vaccine event
      reported by media in 2013 in China caused the costs increased, both benefits and
      the economic values obviously decreased.

PMID- 30107720
TI  - [Research on the relationship between the daily mean temperature and the daily
      cases of varicella during 2008-2016 in Lanzhou, China].
AB  - Objective: To explore the effects of temperature on the daily cases of varicella.
      Methods: The data of daily cases of varicella was collected during 2008 to 2016
      in Lanzhou from National Notifiable Disease Report System, and the meteorological
      data at the same period was integrated from Gansu Meteorological Administration.
      Distributed lag nonlinear model was fitted to reveal the relationship between the
      daily mean temperature and the daily cases of varicella and susceptible
      population. The minimum morbidity temperature was defined as the reference for
      the estimation of RRs in different temperature level (-5.2 C, 1.7 C, 20.1 C and
      25.4 C). Results: The total of 21 254 cases were reported from 2008 to 2016, of
      which the ratio of male to female was 1.28 (11 951/9 303) and people aged 6-14
      years accounted for 52.87%. The relationship between the daily mean temperature
      and the daily cases of varicella was M type. For all subjects, the accumulative
      effects of temperature had statistical significance from lag 0-14 d when
      temperatures was at -5.2 C, 1.7 C and 20.1 C,while the RRs (95%CI) were 1.87
      (1.64-2.12) , 1.33 (1.10-1.62) ,1.60 (1.38-1.86) ,while from lag 0-7 d when
      temperatures was at 25.4 C,and the RR (95%CI) was 2.51 (1.93-3.27) . The RR value
      of accumulative effects was 6.23(95%CI: 4.38-8.86) on lag 7 d when temperatures
      was at -5.2 C, which was the highest value at different temperature during lag
      days. The cumulative effects trends of different temperatures were similar for
      different gender population or different age subjects. However, the cumulative
      effects of was highest for children aged 6-14 years among all subjects, and the
      value of RR was 6.12 (95%CI:3.71-10.10) on lag 5d when temperatures was at -5.2
      C. Conclusion: We conclude that the increasing risk of varicella is associative
      with low and high temperature in Lanzhou. The effects of low temperature are
      stronger than those of high temperature. The children aged 6-14 years belong to
      the high-risk population of varicella.

PMID- 30107721
TI  - [A meta-analysis of the test results of five indicators for hepatitis B virus of
      college freshmen in current mainland China].
AB  - Objective: Using Meta analysis to evaluate the test results of five indicators
      and main infection patterns for hepatitis B virus (HBV) of college freshmen in
      mainland China. Methods: In this paper, "college students", "college freshmen",
      "hepatitis b virus" and "HBV" were used to search systematically for cross
      sectional data of the results of five indicators for HBV of entrants from 2006
      2015 through CNKI, Wanfang Data, VIP as well as Pubmed and Web of Science. Then
      Combie's standard for cross-sectional study was used to assess the qualities of
      the articles included, and Stata 14.0 software and Meta analysis method
      (including performing heterogeneity test, calculating combined detection rates
      and carrying out sensitivity analysis and publication bias test) were used to
      analyze and evaluate the epidemiological significance of the results above.
      Results: Sixteen studies containing 82 144 cases were included. The result of
      heterogeneity test showed that there was significant heterogeneity (P<0.001),
      hence random effects model was adopted. The Meta analysis resulted in total
      positive rate for surface antigen (HBsAg) of 7.0% (95%CI: 6.0%-8.0%), surface
      antibody positive rate (HBsAb) of 46.0% (95%CI: 42.0%-49.0%), and positive rate
      for HBsAg, core antibody (HBcAb) combined with E antigen (HBeAg) or E antibody
      (HBeAb) of 3.0% (95%CI: 2.0%-3.0%) and 3.0% (95%CI: 2.0%-3.0%), respectively;
      whereas the negative rate of all indicators was 41.0% (95%CI: 35.0%-46.0%).
      Sensitivity analysis showed that the results were highly heterogeneous (P<0.001),
      while the result of Egger's regression indicated that there were publication bias
      of all indicators (P<0.05), except for HBsAb (P=0.436). Conclusion: The positive
      rates of HBsAg and HBsAb of college students are lower than those of general
      population, while the positive rates of HBsAg, HBcAb combined with HBeAg or HBeAb
      and the all-negative rate of HBV count for a considerable proportion among
      entrants.

PMID- 30107722
TI  - [Decabromodiphenyl ethane: a review of its pollution levels and toxicity].
AB  - Decabromodiphenyl ethane (DBDPE) is a kind of new brominated flame retardants,
      which is widely used as a replace of decabromodiphenyl ether in electronic
      appliances, textiles and other goods. This review summarizes environmental levels
      and body burden of human beings of DBDPE in recent years. The data shows that the
      concentration of DBDPE in the environment and human tissues shows an upward
      trend. According to limited experiments about its toxicity, DBDPE shows similar
      toxicity to decabromodiphenyl ether. DBDPE can interfere thyroid hormones
      balance, and cause damage to liver, reproductive development, kidney, et al,
      which implies that DBDPE might be another new persistent organic pollutant.
      Further researches are needed.

PMID- 30107723
TI  - [Research progress and enlightenment of HIV infection risk assessment model in
      men who have sex with men].
AB  - The incidence of high-risk sexual behaviors among men who have sex with men (MSM)
      is high, indicating that MSM is the high-risk population of HIV/AIDS, syphilis
      and other sexually transmitted infections (STIs), and also the key population of
      transmission control. However, the risk of HIV infection is different between
      individual MSM due to differences in socio-demographic characteristics, sexual
      characteristics, sexual networks and other factors. It is imperative to establish
      an HIV infection risk assessment model for MSM in China, to allow for MSM to
      quantitatively recognize their risk of HIV infection as well as to allow for
      implementation of tailored HIV prevention and intervention programs targeting MSM
      at greatest risk for HIV infection. The present study reviewed all published HIV
      infection risk assessment models among MSM in the world, and put forward the
      workable methods, potential items and precautions to develop an HIV infection
      risk assessment model among MSM in China.

PMID- 30107724
TI  - [The status of preventive medicine funding supported by National Natural Science
      Foundation of China from 2010-2017].

PMID- 30107725
TI  - Defining the Determinants of Specificity of Plasmodium Proteasome Inhibitors.
AB  - The Plasmodium proteasome is an emerging antimalarial target due to its essential
      role in all the major life cycle stages of the parasite and its contribution to
      the establishment of resistance to artemisinin (ART)-based therapies. However,
      because of a similarly essential role for the host proteasome, the key property
      of any antiproteasome therapeutic is selectivity. Several parasite-specific
      proteasome inhibitors have recently been reported, however, their selectivity
      must be improved to enable clinical development. Here we describe screening of
      diverse libraries of non-natural synthetic fluorogenic substrates to identify
      determinants at multiple positions on the substrate that produce enhanced
      selectivity. We find that selection of an optimal electrophilic "warhead" is
      essential to enable high selectivity that is driven by the peptide binding
      elements on the inhibitor. We also find that host cell toxicity is dictated by
      the extent of coinhibition of the human beta2 and beta5 subunits. Using this
      information, we identify compounds with over 3 orders of magnitude selectivity
      for the parasite enzyme. Optimization of the pharmacological properties resulted
      in molecules that retained high potency and selectivity, were soluble,
      sufficiently metabolically stable and orally bioavailable. These molecules are
      highly synergistic with ART and can clear parasites in a mouse model of
      infection, making them promising leads as antimalarial drugs.

PMID- 30107726
TI  - Octahedral and Porous Spherical Ordered LiNi0.5Mn1.5O4 Spinel: the Role of
      Morphology on Phase Transition Behavior and Electrode/Electrolyte Interfacial
      Properties.
AB  - LiNi0.5Mn1.5O4 compound as positive electrode of the lithium ion battery with
      high specific energy or high specific power, has a good application prospect in
      the field of electric vehicles such as PHEV/EVs. The influence of the morphology
      of ordered LiNi0.5Mn1.5O4 on phase transition behavior and electrode/electrolyte
      interfacial properties is investigated, including octahedral and porous spherical
      morphologies. Three phases named LiNi0.5Mn1.5O4 (Li1), Li0.5Ni0.5Mn1.5O4 (Li0.5)
      and Ni0.5Mn1.5O4 (Li0) are detected by in situ X-ray diffraction (XRD)
      measurement with high time resolution in the octahedral and porous spherical
      ordered LiNi0.5Mn1.5O4 materials during charge and discharge, and the phase
      transition kinetics of the two samples at high discharge rate and after charge
      discharge cycles are elucidated. It is a clear demonstration that the high-rate
      capability and cycle life of LiNi0.5Mn1.5O4 material are influenced by crystal
      morphology. The porous spherical LiNi0.5Mn1.5O4 material exhibits better rate
      performance, associated with the fast reaction kinetic of Li0.5 phase formation.
      It is noticed that the coexistence of three cubic phases in the initial discharge
      stage is observed in the cycled octahedral sample, resulting in a higher capacity
      fading after 200 cycles at room temperature and 1 C. However, the porous
      spherical sample exhibits a poor cyclic performance at 55  degrees C and 1 C.
      This may be attributed to the fact that the porous spherical sample with high
      specific surface area leads to an accelerated decomposition of the electrolyte at
      55  degrees C, and the thick interfacial film and high content of LiF on the
      electrode surface are formed.

PMID- 30107727
TI  - Fabrication of Acidic pH-Cleavable Polymer for Anticancer Drug Delivery Using a
      Dual Functional Monomer.
AB  - The preparation of tumor acidic pH-cleavable polymers generally requires tedious
      postpolymerization modifications, leading to batch-to-batch variation and scale
      up complexity. To develop a facile and universal strategy, we reported in this
      study design and successful synthesis of a dual functional monomer, a-OEGMA that
      bridges a methacrylate structure and oligo(ethylene glycol) (OEG) units via an
      acidic pH-cleavable acetal link. Therefore, a-OEGMA integrates (i) the merits of
      commercially available oligo(ethylene glycol) monomethyl ether methacrylate
      (OEGMA) monomer, i.e., hydrophilicity for extracellular stabilization of
      particulates and a polymerizable methacrylate for adopting controlled living
      radical polymerization (CLRP), and (ii) an acidic pH-cleavable acetal link for
      efficiently intracellular destabilization of polymeric carriers. To demonstrate
      the advantages of a-OEGMA ( Mn = 500 g/mol) relative to the commercially
      available OEGMA ( Mn = 300 g/mol) for drug delivery applications, we prepared
      both acidic pH-cleavable poly(epsilon-caprolactone)21- b-poly( a-OEGMA)11 (PCL21-
      b-P( a-OEGMA)11) and pH-insensitive analogues of PCL21- b-P(OEGMA)18 with an
      almost identical molecular weight (MW) of approximately 5.0 kDa for the
      hydrophilic blocks by a combination of ring-opening polymerization (ROP) of
      epsilon-CL and subsequent atom transfer radical polymerization (ATRP) of a-OEGMA
      or OEGMA. The pH-responsive micelles self-assembled from PCL21- b-P( a-OEGMA)11
      showed sufficient salt stability, but efficient acidic pH-triggered aggregation
      that was confirmed by the DLS and TEM measurements as well as further
      characterizations of the products after degradation. In vitro drug release study
      revealed significantly promoted drug release at pH 5.0 relative to the release
      profile recorded at pH 7.4 due to the loss of colloidal stability and formation
      of micelle aggregates. The delivery efficacy evaluated by flow cytometry analyses
      and an in vitro cytotoxicity study in A549 cells further corroborated greater
      cellular uptake and cytotoxicity of Dox-loaded pH-sensitive micelles of PCL21- b
      P( a-OEGMA)11 relative to the pH-insensitive analogues of PCL21- b-P(OEGMA)18.
      This study therefore presents a facile and robust means toward tumor acidic pH
      responsive polymers as well as provides one solution to the trade-off between
      extracellular stability and intracellular high therapeutic efficacy of drug
      delivery systems using a novel monomer of a-OEGMA with dual functionalities.

PMID- 30107728
TI  - Node-Weighted Amino Acid Network Strategy for Characterization and Identification
      of Protein Functional Residues.
AB  - The study of functional residues (FRs) is essential for understanding protein
      functions and biological processes. The amino acid network (AAN) has become an
      emerging paradigm for studying FRs during the past decade. Current AAN models
      ignore the heterogeneity of nodes and treat amino acids in the AAN as the same.
      However, the properties of each amino acid node are of fundamental importance. We
      here proposed a node-weighted AAN strategy termed the node-weighted amino acid
      contact energy network (NACEN) to characterize and predict three types of FRs,
      namely, hot spots, catalytic residues, and allosteric residues. We first
      constructed NACENs with their nodes weighted based on structural, sequence,
      physicochemical, and dynamical properties of the amino acids and then
      characterized the FRs with the NACEN parameters. We finally built machine
      learning predictors to identify each type of FR. The results revealed that
      residues characterized with NACEN parameters are more distinguishable between FRs
      and non-FRs than those with unweighted network ones. With few features for
      classification, NACEN yields comparable performance for FR identification and
      provides residue level prediction for allosteric regulation. The proposed
      strategy can be easily implemented to other functional residue identification. An
      R package is also provided for NACEN construction and analysis at
      http://sysbio.suda.edu.cn/NACEN/index.html .

PMID- 30107729
TI  - Thrombin-Responsive, Brain-Targeting Nanoparticles for Improved Stroke Therapy.
AB  - Current treatments for ischemic stroke are insufficient. The lack of effective
      pharmacological approaches can be mainly attributed to the difficulty in
      overcoming the blood-brain barrier. Here, we report a simple strategy to
      synthesize protease-responsive, brain-targeting nanoparticles for the improved
      treatment of stroke. The resulting nanoparticles respond to proteases enriched in
      the ischemic microenvironment, including thrombin or matrix metalloproteinase-9,
      by shrinking or expanding their size. Targeted delivery was achieved using
      surface conjugation of ligands that bind to proteins that were identified to
      enrich in the ischemic brain using protein arrays. By screening a variety of
      formulations, we found that AMD3100-conjugated, size-shrinkable nanoparticles
      (ASNPs) exhibited the greatest delivery efficiency. The brain targeting effect is
      mainly mediated by AMD3100, which interacts with CXCR4 that is enriched in the
      ischemic brain tissue. We showed that ASNPs significantly enhanced the efficacy
      of glyburide, a promising stroke therapeutic drug whose efficacy is limited by
      its toxicity. Due to their high efficiency in penetrating the ischemic brain and
      low toxicity, we anticipate that ASNPs have the potential to be translated into
      clinical applications for the improved treatment of stroke patients.

PMID- 30107730
TI  - ProPOSE: Direct Exhaustive Protein-Protein Docking with Side Chain Flexibility.
AB  - Despite decades of development, protein-protein docking remains a largely
      unsolved problem. The main difficulties are the immense space spanned by the
      translational and rotational degrees of freedom and the prediction of the
      conformational changes of proteins upon binding. FFT is generally the preferred
      method to exhaustively explore the translation-rotation space at a fine grid
      resolution, albeit with the trade-off of approximating force fields with
      correlation functions. This work presents a direct search alternative that
      samples the states in Cartesian space at the same resolution and computational
      cost as standard FFT methods. Operating in real space allows the use of standard
      force field functional forms used in typical non-FFT methods as well as the
      implementation of strategies for focused exploration of conformational
      flexibility. Currently, a few misplaced side chains can cause docking programs to
      fail. This work specifically addresses the problem of side chain rearrangements
      upon complex formation. Based on the observation that most side chains retain
      their unbound conformation upon binding, each rigidly docked pose is initially
      scored ignoring up to a limited number of side chain overlaps which are resolved
      in subsequent repacking and minimization steps. On test systems where side chains
      are altered and backbones held in their bound state, this implementation provides
      significantly better native pose recovery and higher quality (lower RMSD)
      predictions when compared with five of the most popular docking programs. The
      method is implemented in the software program ProPOSE (Protein Pose Optimization
      by Systematic Enumeration).

PMID- 30107731
TI  - Maillard-Reacted Whey Protein Isolates Enhance Thermal Stability of Anthocyanins
      over a Wide pH Range.
AB  - The poor thermal and acid stabilities of anthocyanins greatly limit their
      industrial applications as functional food ingredients. This work investigated
      the ability of the Maillard reaction products (MRPs) of whey protein isolates and
      glucose to enhance the thermal stability of anthocyanins over the pH range of 2.0
      7.0. Anthocyanin dispersions were subjected to up to 120 min of thermal treatment
      at 80  degrees C. The improvement in the color stability and antioxidant capacity
      of the anthocyanin dispersions indicated that MRP remarkably inhibited
      anthocyanin degradation. Fluorescence spectroscopy results suggested that
      anthocyanins and MRPs form complexes through hydrophobic interactions. These
      complexes effectively attenuated anthocyanin degradation under heat treatment at
      pH 6.0. The particle sizes of MRPs alone or in complex with anthocyanins remained
      unchanged after heating. The novel protein delivery system proposed in this study
      expands the applications of anthocyanins as acid- and heat-stable functional food
      ingredients.

PMID- 30107732
TI  - Analysis of the Allergenic Epitopes of Tropomyosin from Mud Crab Using Phage
      Display and Site-Directed Mutagenesis.
AB  - Mud crab ( Scylla serrata), which is widely consumed, can cause severe allergic
      symptoms. Eight linear epitopes and seven conformational epitopes of tropomyosin
      (TM) from S. serrata were identified using phage display. The conformational
      epitopes were formed based on the coiled-coil structure of TM. Most of the
      epitopes were located in the regions where primary structures were conserved
      among crustacean TM. Twelve synthetic peptides were designed according to the
      epitopes and trypsin-cutting sites of TM, among them, three synthetic peptides
      (including one linear epitope and two conformational epitopes) were recognized by
      all of the patient sera using inhibitory dot blotting. A triple-variant (R90A
      E164A-Y267A) was constructed based on the critical amino acids of the TM epitope.
      The IgE-binding activity of the triple-variant was significantly reduced compared
      with that of native TM. The results of phage display and site-directed
      mutagenesis offered new information regarding conformational epitopes of TM.

PMID- 30107733
TI  - Characterizing Spatial Diversity of Passive Sampling Sites for Measuring Levels
      and Trends of Semivolatile Organic Chemicals.
AB  - Passive air sampling of semivolatile organic compounds (SVOCs) is a relatively
      inexpensive method that facilitates extensive campaigns with numerous sampling
      sites. An important question in the design of passive-sampling networks concerns
      the number and location of samplers. We investigate this question with the
      example of 17 SVOCs sampled at 14 background sites across the Czech Republic.
      More than 200 time series (length 5-11 years) were used to characterize SVOC
      levels and trends in air between 2003 and 2015. Six polychlorinated biphenyls
      (PCBs), 6 polyaromatic hydrocarbons (PAHs), and 5 organochlorine pesticides
      (OCPs) at 14 sites were assessed using data from the MONET passive sampling
      network. Significant decreases were found for most PCBs and OCPs whereas
      hexachlorobenzene (HCB) and most PAHs showed (mostly insignificant) increases.
      Spatial variability was rather low for PCBs and OCPs except for
      dichlorodiphenyltrichloroethane (DDT) and rather high for PAHs. The variability
      of the SVOC levels and trends depends on characteristics of the sites including
      their remoteness, landscape, population, and pollution sources. The sites can be
      grouped in distinct clusters, which helps to identify similar and, thereby,
      potentially redundant sites. This information is useful when monitoring networks
      need to be optimized regarding the location and number of sites.

PMID- 30107734
TI  - Morphological Control of Coil-Rod-Coil Molecules Containing m-Terphenyl Group:
      Construction of Helical Fibers and Helical Nanorings in Aqueous Solution.
AB  - Rod-coil molecules, composed of rigid segments and flexible coil chains, have a
      strong intrinsic ability to self-assemble into diverse supramolecular
      nanostructures. Herein, we report the synthesis and the morphological control of
      a new series of amphiphilic coil-rod-coil molecular isomers 1-2 containing
      flexible oligoether chains. These molecules are comprised of m-terphenyl and
      biphenyl groups, along with triple bonds, and possess lateral methyl or butyl
      groups at the coil or rod segments. The results of this study suggest that the
      morphology of supramolecular aggregates is significantly influenced by the
      lateral alkyl groups and by the sequence of the rigid fragments in the bulk and
      in aqueous solution. The molecules with different coils self-assemble into
      lamellar or oblique columnar structures in the bulk state. In aqueous solution,
      molecule 1a, with a lack of lateral groups, self-assembled into large strips of
      sheets, whereas exquisite nanostructures of helical fibers were obtained from
      molecule 1b, which incorporated lateral methyl groups between the rod and coil
      segments. Interestingly, molecule 1c with lateral butyl and methyl groups
      exhibited a strong self-organizing capacity to form helical nanorings.
      Nanoribbons, helical fibers, and small nanorings were simultaneously formed from
      the 2a-2c, which are structural isomers of 1a, 1b, and 1c. Accurate control of
      these supramolecular nanostructures can be achieved by tuning the synergistic
      interactions of the noncovalent driving force with hydrophilic-hydrophobic
      interactions in aqueous solution.

PMID- 30107735
TI  - Ionic-Strength Responsive Zwitterionic Copolymer Hydrogels with Tunable Swelling
      and Adsorption Behaviors.
AB  - In this work, we studied the swelling behavior and adsorption behavior of
      zwitterionic copolymer hydrogels, which were prepared via the free radical
      copolymerization of sulfobetaine methacrylate (SBMA) and other monomers including
      sodium p-styrenesulfonate (NaSS), acrylic acid, N-isopropylacrylamide, and 2
      (dimethylamino) ethyl methacrylate. The PSBMA hydrogel showed increased swelling
      ratio with the increase of ionic strength at the same temperature, and the
      swelling process reflected endothermicity. Interestingly, the PSBMA-NaSS
      hydrogels collapsed when the ionic strength increased because the ions can weaken
      the repulsive interaction of the anionic groups of PNaSS. In addition, the PSBMA
      NaSS showed high adsorption of methylene blue (760 mg/g). The zwitterionic
      hydrogels have potential to be used as an adsorbent in the field of wastewater
      treatment.

PMID- 30107736
TI  - Controlled Synthesis of Carbon Nanospheres via the Modulation of the Hydrophilic
      Length of the Assembled Surfactant Micelles.
AB  - A co-polymerization-carbonization method was employed to synthesize porous carbon
      nanospheres (PCNSs) using pyrrole-aniline polymers as a carbon source and alkyl
      phenol non-ionic surfactants as templates. The effect of the hydrophilic length
      on the carbon nanosphere size was systematically investigated. The so-prepared
      PCNSs were characterized via high-magnification scanning electron microscopy,
      dynamic light scattering (DLS) analysis, and N2 adsorption and desorption
      analysis. The results indicate that the obtained nanosphere diameter can be tuned
      by changing the length of the hydrophilic groups. The length of the hydrophilic
      groups mainly affects the size of the vesicles or micelles formed by the assembly
      of the surfactant in solution, as was verified by the DLS results. After
      activation by KOH, the typical sample EO(30)-PCNS has a high specific surface
      area of 2137 m2/g and a large pore volume of 1.76 cm3/g. Electrochemical tests in
      6 M KOH demonstrated that the assembled EO(30)-PCNS supercapacitor electrode
      displays good capacitive properties, such as a high specific capacitance of 221
      F/g at 1.0 A/g and a good rate capacity of 68% retention at 10.0 A/g. This
      finding suggests that the uniform particle shape and high specific surface area
      are beneficial for the ion transportation, leading to good electrochemical
      performances. Our work provides a novel synthetic strategy for the fabrication of
      carbon nanospheres or other nanosphere materials for the construction of high
      performance supercapacitors by optimizing few parameters, such as the length of
      the hydrophilic or hydrophobic groups of the surfactants.

PMID- 30107737
TI  - Synthesis and Nano-object Assembly of Biomimetic Block Copolymers for Catalytic
      Silver Nanoparticles.
AB  - Biomimetic ABC triblock copolymers of poly[2-(methacryloyloxy)ethyl
      phosphorylcholine]- b-poly[2-(dimethylamino)ethyl methacrylate]- b-poly(2
      hydroxypropyl methacrylate) (PMPC- b-PDMA- b-PHPMA) were synthesized by RAFT
      aqueous dispersion polymerization of 2-hydroxypropyl methacrylate (HPMA) in the
      presence of a PMPC- b-PDMA macromolecular chain transfer agent (macro-CTA). This
      ABC triblock copolymer deploys well-known biocompatible PMPC and PDMA for the
      coordination of Ag+ ions to form silver nanoparticles in situ on reduction, and
      PHPMA for assembling (core) in water. The synthesis of PMPC- b-PDMA- b-PHPMA
      starts when both the reactive steric stabilizer of PMPC25- b-PDMA4 macro-CTA and
      HPMA monomer are dissolved in water. The growing PHPMA is not soluble in water
      and begins to assemble based on three-layer onion micelles, in which the outer
      and inner shells are PMPC and PDMA, respectively. In the synthesis of PMPC25- b
      PDMA4- b-PHPMA z at a constant 25% (w/w) solids concentration, the resultant
      assemblies change from spheres to worms to jellyfishes to vesicles when the
      targeted PHPMA chain length increases from 100mer to 400mer at full monomer
      conversion. Furthermore, in the synthesis of identical PMPC25- b-PDMA4- b
      PHPMA400 copolymers, the assembly morphology can be controlled from vesicles to
      spheres through worms by varying the solids concentration in the polymerization
      mixture, decreasing from 25% (w/w) to 15% (w/w) at full monomer conversion. Thus,
      the final morphology can be tuned by the degree of polymerization of HPMA and the
      solids concentration in the polymerization mixture. Using the resultant three
      PMPC25- b-PDMA4- b-PHPMA400 assemblies as scaffolds, Ag(0) nanoparticles (Ag-NPs)
      are obtained through in situ reduction of AgNO3 facilitated by electrostatic
      interactions between the Ag+ ions and PDMA moieties. The resultant Ag-NPs loaded
      in the assemblies exhibit excellent stability, dispersibility, and activity of
      catalyst for the reduction of p-nitrophenol. The order of rate constants for the
      reduction using Ag-NPs loaded in the assemblies is worms > vesicles > spheres,
      which corresponds to the order of the surface areas of the assemblies of PMPC25-
      b-PDMA4- b-PHPMA400. These results can be achieved thanks to the kinetically
      frozen PMPC25- b-PDMA4- b-PHPMA400 assemblies with identical compositions.

PMID- 30107738
TI  - Identification, Quantification, and Anti-inflammatory Activity of 5- n
      Alkylresorcinols from 21 Different Wheat Varieties.
AB  - The characteristic constituent and anti-inflammatory activity of 5- n
      alkylresorcinols (ARs) from 21 wheat bran samples in China were investigated in
      this study. The amount of ARs ranged from 697 to 1732 MUg/g in the tested
      samples, which were composed of five different homologues. Among these
      homologues, C19:0 and C21:0 were the most abundant, followed by C17:0, C23:0, and
      C25:0. Moreover, the mRNA expression of IL-1beta, IL-6, and TNF-alpha in LPS
      activated RAW264.7 macrophage cells were significantly inhibited by ARs
      supplementation. The molecular mechanisms behind its anti-inflammatory activity
      could result from the suppression of nuclear factor-kappaB (NF-kappaB) and
      JNK/MAPK activation. ARs treatment notably decreased NF-kappaB p65 nuclear
      translocation and inhibitor kappaB (IkappaBalpha) kinase and JNK phosphorylation.
      Additionally, ARs homologues C17:0 had been proven to be the main active
      constituent. The results from this study could be used to promote the
      comprehensive utilization of wheat and its byproducts in improving human health.

PMID- 30107739
TI  - Water Structure Controls Carbonic Acid Formation in Adsorbed Water Films.
AB  - Reaction pathways and kinetics in highly structured H2O adsorbed as Angstrom to
      nanometer thick layers on mineral surfaces are distinct from those facilitated by
      bulk liquid water. We investigate the role of the interfacial H2O structure in
      the reaction of H2O and CO2 to form carbonic acid (H2CO3) in thin H2O films
      condensed onto silica nanoparticles from humidified supercritical CO2. Rates of
      carbonic acid formation are correlated with spectroscopic signatures of H2O
      structure using oxygen isotopic tracers and infrared spectroscopy. While carbonic
      acid virtually does not form in the supercritical phase, the silica surface
      catalyzes this reaction by concentrating H2O through adsorption at hydrophilic
      silanol groups. Within measurement uncertainty, we found no evidence that
      carbonic acid forms when exclusively ice-like structured H2O is detected at the
      silica surface. Instead, formation of H2C18O16O2 from H218O and C16O2 was found
      to be linearly correlated with liquid-like structured H2O that formed on the ice
      like layer.

PMID- 30107741
TI  - In This Issue, Volume 9, Issue 8.

PMID- 30107740
TI  - Functional Biointerfaces Based on Mixed Zwitterionic Self-Assembled Monolayers
      for Biosensing Applications.
AB  - Surface modification for biosensors has focused attention for improvement of
      their sensitivity and specificity, particularly for the detection in complex
      medium. In this work, we have synthesized zwitterionic carboxybetaine-thiols (CB
      thiols) and sulfobetaine-thiols (SB-thiols) for modification of gold substrates
      to form a functional self-assembled monolayer (SAM) for the immunoassay in a
      surface plasmon resonance (SPR) biosensor. X-ray photoelectron spectroscopy
      (XPS), contact angle goniometer, and cyclic voltammetry were applied for
      characterizations of elemental composition, surface wettability, and packing
      density, respectively. The antifouling properties of the SAMs were accessed by
      quantitative analysis of protein and bacterial adsorption. The results from the
      SAMs with a single component indicated that the SB-thiol SAM provides better
      surface hydrophilicity, fouling resistance, and packing density as compared to
      the CB-thiol SAM, likely due to the ionic association of CB moieties. However,
      the CB-thiol with the functional carboxylate group plays a critical role in
      postmodification of biomolecules via commercially available amine coupling
      chemistry. Thus, the mixed SAMs were prepared to integrate the unique
      characteristics from CB- and SB-thiols to control compositions and surface
      properties. The immunoassay was performed in the SPR biosensor, showing that the
      zwitterionic mixed SAM enables immobilization of biorecognition elements (BREs),
      and improved sensitivity and specificity. Consequently, the work reveals
      excellent and attractive versatility, antifouling, and functionalizable
      properties of zwitterionic mixed SAMs comprising CB- and SB-thiols for biosensing
      applications. This surface chemistry is expected to be applicable to monitor
      specific molecular recognition events.

PMID- 30107742
TI  - Animal Model Systems in Neuroscience.

PMID- 30107743
TI  - Pharmacokinetic and Pharmacodynamic Profiles of Glyco-Modified Atrial Natriuretic
      Peptide Derivatives Synthesized Using Chemo-enzymatic Synthesis Approaches.
AB  - Atrial natriuretic peptide (ANP) exerts beneficial pharmacological effects in the
      treatment of various cardiovascular disorders, such as acute congestive heart
      failure (ADHF). However, the clinical use of ANP is limited to the continuous
      intravenous infusion owing to its short half-life (2.4 +/- 0.7 min). In the
      present study, we conjugated the glyco-modified ANP with a monoclonal antibody
      (mAb) or an Fc via chemo-enzymatic glyco-engineering using EndoS D233Q/Q303L. The
      most potent derivative SG-ANP-Fc conjugate extended the half-life to 14.9 d and
      the duration of blood pressure lowering effect to over 28 d. This new biologic
      modality provides an opportunity to develop outpatient therapy after ADHF.

PMID- 30107745
TI  - Gold Coating of Silver Nanoplates for Enhanced Dispersion Stability and Efficient
      Antimicrobial Activity against Intracellular Bacteria.
AB  - Silver nanoparticles have antibacterial activity. However, the nanoparticles are
      unstable and easily form aggregates, which decreases their antibacterial
      activity. To improve the dispersion stability of silver nanoparticles in aqueous
      media and to increase their effectiveness as antibacterial agents, we coated
      triangular plate-like silver nanoparticles (silver nanoplates, Ag NPLs) with one
      or two layers of gold atoms (Ag@Au1L NPLs and Ag@Au2L NPLs, respectively). These
      gold coatings improved the dispersion stability in aqueous media with high salt
      concentrations. Ag@Au1L NPLs showed stronger antibacterial activity on pathogenic
      bacteria than Ag NPLs and Ag@Au2L NPLs. Furthermore, the Ag@Au1L NPLs decreased
      the number of bacteria in RAW 264.7 cells. The Ag@Au1L NPLs displayed no
      cytotoxicity towards RAW 264.7 cells and could be used as antibacterial agents
      for intracellular bacterial infections.

PMID- 30107746
TI  - Surface Passivation of Bismuth-Based Perovskite Variant Quantum Dots To Achieve
      Efficient Blue Emission.
AB  - Metal halide perovskite quantum dots (QDs) recently have attracted great research
      attentions. However, blue-emitting perovskite QDs generally suffer from low
      photoluminescence quantum yield (PLQY) because of easily formed defects and
      insufficient surface passivation. Replacement of lead with low toxicity elements
      is also preferred toward potential commercial applications. Here, we apply Cl
      passivation to boost the PLQY of MA3Bi2Br9 QDs to 54.1% at the wavelength of 422
      nm, a new PLQY record for blue emissive, lead-free perovskite QDs. Because of the
      incompatible crystal structures between MA3Bi2Br9 and MA3Bi2Cl9 and the careful
      kinetic control during the synthesis, Cl- anions are engineered to mainly locate
      on the surface of QDs acting as passivating ligands, which effectively suppress
      surface defects and enhance the PLQY. Our results highlight the potential of
      MA3Bi2Br9 QDs for applications of phosphors, scintillators, and light-emitting
      diodes.

PMID- 30107748
TI  - Reducing Dendrimer Generation and PEG Chain Length Increases Drug Release and
      Promotes Anticancer Activity of PEGylated Polylysine Dendrimers Conjugated with
      Doxorubicin via a Cathepsin-Cleavable Peptide Linker.
AB  - PEGylation typically improves the systemic exposure and tumor biodistribution of
      polymeric drug delivery systems, but may also restrict enzyme access to peptide
      based drug linkers. The impact of dendrimer generation (G4 vs G5) and PEG length
      (570 vs 1100 Da) on the pharmacokinetics, tumor biodistribution, drug release
      kinetics, and anticancer activity of a series of PEGylated polylysine dendrimers
      conjugated with doxorubicin via a cathepsin-B cleavable valine-citrulline linker
      was therefore investigated in rodents. Although the smallest G4 PEG570 dendrimer
      showed the most efficient cathepsin-mediated doxorubicin release, systemic
      exposure and tumor uptake were limited. The largest G5 PEG1100 dendrimer showed
      good tumor uptake and retention but restricted drug liberation and therefore
      limited anticancer activity. Superior anticancer activity was achieved using an
      intermediate sized dendrimer that showed better drug release kinetics, systemic
      exposure, tumor uptake, and retention. The data suggest that balancing PEG
      molecular weight and dendrimer size is critical when designing chemotherapeutic
      dendrimers.

PMID- 30107747
TI  - Polymeric Caffeic Acid Is a Safer Mucosal Adjuvant That Augments Antigen-Specific
      Mucosal and Systemic Immune Responses in Mice.
AB  - Infections remain a major threat to human lives. To overcome the threat caused by
      pathogens, mucosal vaccines are considered a promising strategy. However, no
      inactivated and/or subunit mucosal vaccine has been approved for human use,
      largely because of the lack of a safe and effective mucosal adjuvant. Here, we
      show that enzymatically synthesized polymeric caffeic acid (pCA) can act as a
      potent mucosal adjuvant in mice. Intranasal administration of ovalbumin (OVA) in
      combination with pCA resulted in the induction of OVA-specific mucosal IgA and
      serum IgG, especially IgG1. Importantly, pCA was synthesized from caffeic acid
      and horseradish peroxidase from coffee beans and horseradish, respectively, which
      are commonly consumed. Therefore, pCA is believed to be a highly safe material.
      In fact, administration of pCA did not show distinct toxicity in mice. These data
      indicate that pCA has merit for use as a mucosal adjuvant for nasal vaccine
      formulations.

PMID- 30107749
TI  - Access to medicines for hypertension: a survey in rural Yogyakarta province,
      Indonesia.
AB  - INTRODUCTION: Obtaining an adequate supply of medicines is an important step in
      facilitating medication adherence. This study aimed to determine (1) how people
      with hypertension in rural villages in Indonesia obtain their supply of anti
      hypertensive medications, (2) the type of hypertension medication taken and (3)
      factors associated with where and how people obtain their medicines supplies.
      METHOD: Data pertaining to people with hypertension (age &ge;45 years) were
      collected from eight rural villages in the Bantul district, Yogyakarta province,
      Indonesia, using a researcher-administered questionnaire. RESULTS: Of 384
      participants, 203 (52.9%) obtained anti-hypertensive medications from public or
      private healthcare services. The most common way was by purchasing these
      medicines without prescription in community pharmacies (n=64, 17%). The medicines
      obtained this way included captopril, amlodipine, nifedipine, and bisoprolol. One
      hundred and nineteen (15%) participants obtained their medicines at no cost by
      visiting public healthcare services such as community health centres (n=51), the
      Integrated Health Service Post for the Elderly (n=53), and the public hospitals
      (n=15). Direct dispensing from clinicians was reported by participants who
      visited a doctor (n=15), midwife (n=23) or nurse (n=21). Having access to an
      adequate medication supply (ie for an entire 30 days) was reported by 40 (10.4%)
      participants, who obtained the medication from a community health centre (n=18),
      public hospital (n=4), community pharmacy (n=5), private hospital (n=2), or
      multiple sources (n=11). A higher formal education level was associated with
      obtaining medicines from multiple sources rather than from the public or private
      provider only. Living near a community health centre and having government
      insurance were associated with obtaining medicines from the public health
      service. Age, gender, employment, presence of other chronic diseases, and
      knowledge about hypertension were not significantly associated with how
      participants obtained their medications. CONCLUSION: These Indonesian
      participants obtained their anti-hypertensive medications from various sources;
      however, the inadequate supplies found in this study could compromise both short-
      and long-term management of hypertension. Direct dispensing, non-doctor
      prescribing, and self-medication with anti-hypertensive medications indicate the
      current complex healthcare system in Indonesia. This study also shows some
      challenges involved in managing patients with chronic diseases such as
      hypertension in resource-poor settings. It provides important findings for
      quality improvement practices that should be considered to improve the health
      lifespan in populous countries such as Indonesia.

PMID- 30107750
TI  - The Supervision Pyramid: A Commonalities-Based Synthesis of Intervention,
      Relationship, and Person/Personhood.
AB  - Adapting the therapeutic pyramid to the supervision of psychotherapy, the author
      presents and describes the supervision pyramid-a simple meta-model of the broad
      conceptual organizers of the supervisor's contribution to the experience and
      outcomes of supervision. The supervision pyramid consists of three commonalities:
      supervisor skills and interventions, the supervisory relationship, and the
      supervisor's person and personhood. Those three commonalities converge to
      stimulate supervisee learning and relearning and client improvement and symptom
      reduction. The implications of this meta-model for supervision conceptualization
      and conduct and for supervisor training are briefly described.

PMID- 30107751
TI  - Tissue-based multigene expression tests for pretreatment prostate cancer risk
      assessment: current status and future perspectives.
AB  - Prostate cancer is a highly prevalent disease with ample spectrum of
      aggressiveness and treatment options. Low-risk disease can be safely managed by
      nonintervention strategies, such as active surveillance; however, accurate risk
      assessment is warranted. Molecular tests have been developed and validated to
      complement standard clinicopathological parameters and help to improve risk
      stratification in prostate cancer. Herein, we review selected tissue-based
      assays, including genomic prostate score, cell cycle progression score and
      genomic classifier, with particular emphasis on their role in patient risk
      assessment in a pretreatment setting, in view of their current or potential
      utilization in active surveillance.

PMID- 30107752
TI  - Measuring the impact of the 2012 European pharmacovigilance legislation on
      additional risk minimization measures.
AB  - AIMS: Additional risk minimization measures (aRMMs) may be needed to ensure that
      the benefits continue to outweigh the risks for medicines associated with serious
      risks. Prior research showed an increasing trend in medicines with aRMMs. We
      assessed whether the European pharmacovigilance legislation may have impacted the
      number and type of aRMMs. METHODS: We included new active substances approved
      between 1 January 2010 and 31 December 2015. Information extracted from the
      summary of the Risk Management Plan at the time of licensing included date and
      type of marketing authorization, presence and type of aRMMs. We tested for
      differences using Pearson's Chi2 test and segmented Poisson regression. RESULTS:
      We identified 231 medicines approved during the study period, of which 30% had
      aRMMs at the time of licensing. ARMMs were in place for 38% of medicines before
      July 2012 and for 28% after (p = 0.16). Segmented Poisson regression did not show
      changes in trend or level of medicines with aRMMs. DISCUSSION AND CONCLUSION:
      During the study period, no significant differences in the proportion or trend of
      products with aRMMs at the time of licensing before and after the
      pharmacovigilance legislation were identified.

PMID- 30107754
TI  - Qualitative evaluation of a guideline supporting shared decision making for
      extreme preterm birth.
AB  - BACKGROUND AND OBJECTIVES: The decision to attempt resuscitation or provide
      palliative care at birth for extremely preterm infants between 22 and 25 weeks
      remains complex. The purpose of this study was to identify facilitators and
      barriers to implementation of a clinical practice guideline developed to support
      shared decision-making for these cases. METHODS: A purposeful sample of
      healthcare providers, involved in the care of one of five cases of anticipated
      extremely preterm birth, was recruited for interviews. Participants shared their
      views on the guideline content, implementation process, and facilitators and
      barriers encountered. Interviews were audio-recorded and transcribed verbatim.
      Qualitative content analysis was used to code, categorize, and thematically
      describe the data. The Knowledge-Attitudes-Behaviours framework was used to
      organize the findings. RESULTS: Twenty-five key informants (16 physicians, nine
      nurses) were interviewed. Participants described varying levels of knowledge of
      the guideline. Facilitators to implementation included: (1) an awareness of,
      familiarity with and belief in the content; (2) hard copy and electronic
      guideline accessibility; and, (3) institutional expertise to provide necessary
      care. Barriers included: (1) minimal awareness or familiarity with the content;
      (2) lack of agreement with the recommendations; (3) inadequate evidence and
      applicability to support changes in practice; and, (4) lack of resources to care
      for the most immature infants. CONCLUSIONS: Identified facilitators and barriers
      will inform the development of tailored strategies for improved local and future
      broader implementation. Other institutions can use the results to facilitate
      implementation of their guidelines on this ethically charged area.

PMID- 30107753
TI  - Clinical and imaging characteristics of subacute combined degeneration
      complicated with white matter lesions in the brain: a report of five cases.
AB  - PURPOSE: To report five cases of subacute combined degeneration (SCD) with brain
      involvement and explore its clinical and imaging characteristics. METHODS: A
      retrospective study was performed on the clinical data and brain MRI of five
      patients with subacute combined degeneration with brain involvement (out of 107
      cases with SCD in total). White matter lesions (WML) assessment was performed
      qualitatively using Fazekas scale score. RESULTS: The main symptoms in four
      patients were weakness in both lower extremities and unstable walking (limb
      weakness in three patients, dizziness in three patients, and blurred vision in
      one patient). One patient had memory loss and cognitive dysfunction. The MMSE
      scale indicated mild dementia in one patient. On head MRI (Magnetic Resonance
      Imaging), multifocal and symmetrical high signals of T2WI and FLAIR were observed
      in the frontal lobe and periventricular white matter in four patients, while
      another patient showed preferential atrophy in frontal regions. Fazekas scale
      scores ranged from 1-6. CONCLUSION: Adult subacute combined degeneration seldom
      involves the brain. Multifocal and symmetrical high signal white matter lesions
      can be found on FLAIR and T2WI, as well as frontal atrophy on head MRI.

PMID- 30107755
TI  - Lidocaine-prilocaine cream versus local infiltration anesthesia in pain relief
      during repair of perineal trauma after vaginal delivery: a systematic review and
      meta-analysis.
AB  - BACKGROUND: Perineal trauma is a common problem that may affect women during
      vaginal delivery; this trauma can be either spontaneous (tear) or intentional
      (episiotomy). When repair of perineal trauma is required, adequate analgesics
      must be obtained. Topical products as lidocaine-prilocaine (EMLA) cream is one of
      the suggested methods, but still there is lack of evidence with regard to its
      efficacy and safety. OBJECTIVE: The aim of this review is to assess the evidence
      of utilizing EMLA cream in comparison to local perineal infiltration anesthesia
      for pain control during perineal repair after vaginal delivery. DATA SOURCES:
      Medline, Embase, Dynamed Plus, ScienceDirect, TRIP database, ClinicalTrials.gov
      and the Cochrane Library were searched electronically from January 2006 to May
      2018 for studies investigating the effect of lidocaine-prilocaine cream in
      relieving pain during repair of perineal trauma. METHODS OF STUDY SELECTION: All
      randomized controlled trials assessing effect of lidocaine-prilocaine cream
      versus local infiltration anesthesia in relieving pain during repair of perineal
      trauma were considered for this meta-analysis. Fifteen studies were identified of
      which four studies deemed eligible for this review. Quality and risk of bias
      assessment was performed for all studies. DATA EXTRACTION: Two researchers
      independently extracted the data from the individual articles and entered into
      RevMan software. The weighted mean difference (WMD) and 95% confidence interval
      (CI) was calculated. Statistical heterogeneity between studies was assessed by
      the Higgins chi-square and (I2) statistics. When heterogeneity was significant, a
      random-effects model was used for meta-analysis. Otherwise, the fixed effect meta
      analysis was used when there was no significant heterogeneity. RESULTS: Pooled
      analysis of result in "pain score" was insignificant between the two groups (WMD 
      1.11; 95% CI (-2.55 to 0.33); p = .13). Furthermore, the use of additional
      analgesia showed no statistically significant difference between the two groups
      (WMD 1.34; 95% CI (0.66-2.71), p = .42). Regarding patient satisfaction, an
      overall analysis of three studies showed significant results favoring EMLA cream
      group users (WMD 4.65; 95% CI (1.96-11.03), p = .0005). The pooled analysis of
      the outcome "duration of repair" showed the significantly shorter duration of
      repair in EMLA cream users (n = 92) than local infiltration anesthesia (n = 95)
      (1.72 min; 95% CI (-2.76 to -0.67), p = .001). CONCLUSIONS: This meta-analysis
      suggests that topical lidocaine-prilocaine cream gives comparable results in
      reducing pain during perineal repair after vaginal delivery.

PMID- 30107756
TI  - Perineal massage during labor: a systematic review and meta-analysis of
      randomized controlled trials.
AB  - BACKGROUND: Different techniques have been analyzed to reduce the risk of
      perineal trauma during labor. OBJECTIVE: To evaluate whether perineal massage
      techniques during vaginal delivery decreases the risk of perineal trauma. SEARCH
      STRATEGY: Electronic databases (Medline, Prospero, Scopus, ClinicalTrials.gov,
      Embase, ScienceDirect, the Cochrane Library, SciELO) were searched from their
      inception until February 2018. No restrictions for language or geographic
      location were applied. SELECTION CRITERIA: We included all randomized controlled
      trials (RCTs) comparing the use of perineal massage during labor (i.e.
      intervention group) with a control group (i.e. no perineal massage) in women with
      singleton gestation and cephalic presentation at >=36 weeks. Perineal massage was
      defined as massage of the posterior perineum by the clinician's fingers (with or
      without lubricant). Trials on perineal massage during antenatal care, before the
      onset of labor, or only in the early part of the first stage, were not included.
      DATA COLLECTION AND ANALYSIS: All analyses were done using an intention-to-treat
      approach. The primary outcome was severe perineal trauma, defined as third and
      fourth degree perineal lacerations. Meta-analysis was performed using the random
      effects model of DerSimonian and Laird to produce summary treatment effects in
      terms of either a relative risk (RR) with 95% confidence interval (CI). MAIN
      RESULTS: Nine trials including 3374 women were analyzed. All studies included
      women with singleton pregnancy in cephalic presentation at >=36 weeks undergoing
      spontaneous vaginal delivery. Perineal massage was usually done by a midwife in
      the second stage, during or between and during pushing time, with the index and
      middle fingers, using a water-soluble lubricant. Women randomized to receive
      perineal massage during labor had a significantly lower incidence of severe
      perineal trauma, compared to those who did not (RR 0.49, 95% CI 0.25-0.94). All
      the secondary outcomes were not significant, except for the incidence of intact
      perineum, which was significantly higher in the perineal massage group (RR 1.40,
      95% 1.01-1.93), and for the incidence of episiotomy, which was significantly
      lower in the perineal massage group (RR 0.56, 95% CI 0.38-0.82). CONCLUSIONS:
      Perineal massage during labor is associated with significant lower risk of severe
      perineal trauma, such as third and fourth degree lacerations. Perineal massage
      was usually done by a midwife in the second stage, during or between and during
      pushing time, with the index and middle fingers, using a water-soluble lubricant.

PMID- 30107757
TI  - Challenges for programmatic implementation of killed whole cell oral cholera
      vaccines for prevention and control of cholera: a meta-opinion.
AB  - INTRODUCTION: Cholera remains a public health threat. The development of safe,
      effective, easy-to-administer, heat-stable, and cheap killed whole cell oral
      cholera vaccines (OCVs) has provided an additional tool to counter cholera. In
      this meta-opinion, we review the challenges of delivering OCVs through the
      existing public health infrastructure in vulnerable areas. Areas covered: We
      provide an overview of the available vaccines against cholera, the existing
      evidence about the effectiveness of a two-dose as well as a single-dose OCV
      strategy. We also highlight the experience from the public health campaigns for
      OCV deployment. Expert opinion: Several public health experiences have shown the
      feasibility of incorporating OCVs into the public health response against
      cholera. Combined with a comprehensive water, sanitation, and hygiene (WaSH)
      improvement plan, OCVs need to be deployed in identified vulnerable areas,
      targeting the highest risk groups first. Vaccination programs should not be
      deployed in lieu of investments in WaSH services, but as a complimentary service
      in a comprehensive, cholera control intervention package. It has been a challenge
      to have high two-dose coverage across all eligible recipients, necessitating the
      adoption of innovative strategies to boost coverage. Longer intervals between
      doses may help to overcome resource and logistical limitations enabling higher
      coverage.

PMID- 30107758
TI  - Patient satisfaction after thyroid RFA versus surgery for benign thyroid nodules:
      a telephone survey.
AB  - INTRODUCTION: Minimally invasive nonsurgical techniques are gaining ground as
      alternatives to surgery for the treatment of benign thyroid nodules. Here, we
      aimed at comparing patient satisfaction after radiofrequency ablation (RFA) to
      that after surgery. METHODS: In this cross-sectional study, we recruited 126
      patients treated with RFA and 84 treated with surgery for a single benign thyroid
      nodule. All patients were contacted by phone call and were asked the following
      questions: Are you satisfied with the symptom resolution?; Are you satisfied with
      the cosmetic results?; Are you satisfied overall with the procedure?; Are you
      taking any medication for your thyroid? Patients' general characteristics were
      collected from our database. RESULTS: In the surgery group, there was a higher
      percentage of patients fully satisfied with the resolution of nodule-related
      symptoms (p = .02). In the RFA group, there was a higher percentage of patients
      fully satisfied with the cosmetic results (p = .001). In terms of overall
      satisfaction, there were no differences between the groups (p = .26).
      Nevertheless, RFA led to differing results based on thyroid nodule function. In
      patients with nonfunctioning thyroid nodules, RFA was as effective as surgery in
      terms of satisfaction with symptom resolution, while it was not in patients with
      autonomously functioning thyroid nodules (AFTN). CONCLUSION: Our data on
      postoperative patient satisfaction support the notion that both RFA and surgery
      are valid therapeutic options for nonfunctioning thyroid nodules, while surgery
      should be still preferred for AFTN.

PMID- 30107759
TI  - Immunological mechanisms underlying chronic rhinosinusitis with nasal polyps.
AB  - INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common and
      quality-of-life impacting disorder, with an underlying immunological mechanism
      similar to other conditions such as eosinophilic asthma or atopic eczema. Areas
      covered: This review article summarizes the most recent evidence on the main
      immunological mechanisms involved in the pathogenesis and the perpetuation of
      CRSwNP, with a particular focus on the key role of epithelium-derived
      inflammation as a consequence of the interaction with the airborne environment.
      Expert commentary: The increase in knowledge of the immunology of CRSwNP leads to
      the development of therapeutical strategies based upon the use of biologic agents
      that, according to a personalized and precision medicine approach, will provide
      each single patient with the most suitable immunological treatment.

PMID- 30107762
TI  - Comparative effectiveness of avelumab versus chemotherapy in Merkel cell
      carcinoma: innovative use of patient insights.
AB  - AIM: To assess patient experience with chemotherapy and avelumab in metastatic
      Merkel cell carcinoma (mMCC). METHODS: In the JAVELIN Merkel 200 trial,
      chemotherapy-refractory mMCC patients could participate in optional qualitative
      interviews at baseline documenting recollection of previous chemotherapy
      experience, and at weeks 13/25 documenting current experience with avelumab.
      Functional Assessment of Cancer Therapy subscale for melanoma questionnaire (FACT
      M) was administered in parallel. RESULTS: In our sample, chemotherapy was
      associated with an unpleasant experience. On selected FACT-M items addressing
      chemotherapy-impacted concepts, most patients receiving avelumab were improved or
      stable; few worsened. In addition, a few patients spontaneously reported
      experiencing less toxicity with avelumab than experienced during previous
      chemotherapy. CONCLUSION: This approach merging qualitative and quantitative data
      suggests that mMCC patients report a better experience with avelumab than with
      chemotherapy.

PMID- 30107761
TI  - Comparison of unpleasant and pain thresholds of thermal stimuli in the orofacial
      regions: a psychophysical study using quantitative sensory testing in healthy
      young men.
AB  - : Purpose/Aim: To gain a better understanding of the psychophysics of thermal
      pain perception in a clinical setting, this study investigated whether thermal
      thresholds of unpleasantness are different from pain thresholds of cold and heat
      stimuli. Of particular interest was the relationship between unpleasantness and
      pain thresholds for cold vs heat stimuli. MATERIAL AND METHODS: Thirty healthy
      male volunteers (mean age 26.1 years, range 23 to 32 years) participated. Thermal
      detection, cold pain (CPT) and heat pain (HPT) thresholds were measured at 5
      trigeminal sites by the method of limits using quantitative sensory testing
      (QST), followed by cold unpleasant (CUT) and heat unpleasant (HUT) thresholds.
      RESULTS: The temperatures at which individuals first reported thermal sensations
      as unpleasant or painful substantially differed among subjects. CUT exhibited a
      higher mean value with less variability than CPT, and HUT presented a lower mean
      than HPT (p < .001). As with CPT, CUT did not show any significant difference
      between the test sites. On the other hand, HUT, like HPT, exhibited site
      differences (p < .001). There was moderate correlation between CUT and CPT,
      whereas HUT and HPT were strongly correlated. The relationship between unpleasant
      and pain thresholds of cold vs heat stimuli was significantly different even when
      controlling for test site variability (p < .001). CONCLUSION: These findings
      indicate that unpleasant and pain thresholds to thermal stimuli differ in healthy
      young men. Of particular note is the distinct relationship of unpleasant and pain
      thresholds of cold vs heat stimuli, revealing the thermal difference in
      temperature transition from unpleasantness to pain.

PMID- 30107760
TI  - Curcumin-loaded PLGA-PEG nanoparticles conjugated with B6 peptide for potential
      use in Alzheimer's disease.
AB  - Alzheimer's disease is a neurodegenerative disorder mainly characterized by beta
      amyloid deposit and tau hyperphosphorylation with no curative treatments.
      Curcumin (Cur) has been proved to have potential use in Alzheimer's disease with
      its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However,
      its hydrophobicity and low bioavailability hinder its application. In this paper,
      we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block
      poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with
      Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al
      transgenic mice. The in vitro assays including dynamic light scattering (DLS),
      flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG)
      analysis indicated that this nanoparticle could narrow the diameter of Cur,
      increase its cellular uptake and possess good blood compatibility. The results
      from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the
      spatial learning and memory capability of APP/PS1 mice, compared with native Cur.
      The ex vivo assays including Bielschowsky silver staining, immunostaining, and
      western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal beta
      amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested
      that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for
      the treatment of Alzheimer's disease.

PMID- 30107763
TI  - Dr Google in the ED: searching for online health information by adult emergency
      department patients.
AB  - OBJECTIVE: To determine the prevalence, predictors, and characteristics of health
      related internet searches by adult emergency department (ED) patients; to examine
      the effect of searching on the doctor-patient relationship and treatment
      compliance. DESIGN: A multi-centre, observational, cross-sectional study; a
      purpose-designed 51-item survey, including tools for assessing e-health literacy
      (eHEALS) and the effects of internet searching on the doctor-patient relationship
      (ISMII). Setting, participants: 400 adult patients presenting to two large
      tertiary referral centre emergency departments in Melbourne, February-May 2017.
      OUTCOME MEASURES: Descriptive statistics for searching prevalence and
      characteristics, doctor-patient interaction, and treatment compliance; predictors
      of searching; effect of searching on doctor-patient interaction. RESULTS: 400 of
      1056 patients screened for eligibility were enrolled; their mean age was 47.1
      years (SD, 21.1 years); 51.8% were men. 196 (49.0%) regularly searched the
      internet for health information; 139 (34.8%) had searched regarding their current
      problem before presenting to the ED. The mean ISMII score was 30.3 (95% CI, 29.6
      31.0); searching improved the doctor-patient interaction for 150 respondents
      (77.3%). Younger age (per 10-year higher age band: odds ratio [OR], 0.74; 95% CI,
      0.61-0.91) and greater e-health literacy (per one-point eHEALS increase: OR,
      1.11; 95% CI, 1.06-1.17) predicted searching the current problem prior to
      presentation; e-health literacy predicted ISMII score (estimate, 0.39; 95% CI,
      0.20-0.39). Most patients would never or rarely doubt their diagnosis (79%) or
      change their treatment plan (91%) because of conflicting online information.
      CONCLUSION: Online health care information was frequently sought before
      presenting to an ED, especially by younger and e-health literate patients.
      Searching had a positive impact on the doctor-patient interaction and was
      unlikely to reduce adherence to treatment.

PMID- 30107765
TI  - Screening for spinal muscular atrophy.

PMID- 30107766
TI  - A shift in scholarly publishing practices and the growing menace of predatory
      journals.

PMID- 30107767
TI  - Network meta-analysis in health care decision making.

PMID- 30107768
TI  - Bee sting to the cornea: toxic effects and management.

PMID- 30107769
TI  - Navigating and negotiating complex clinical scenarios.

PMID- 30107770
TI  - Inequity amplified: climate change, the Australian farmer, and mental health.

PMID- 30107771
TI  - Improved relative survival of patients with B-cell non-Hodgkin lymphoma in
      Queensland, 1993-2012.

PMID- 30107772
TI  - Management of bronchiectasis in adults.
AB  - Once neglected in research and underappreciated in practice, there is renewed
      interest in bronchiectasis unrelated to cystic fibrosis. Bronchiectasis is a
      chronic lung disease characterised by chronic cough, sputum production and
      recurrent pulmonary exacerbations. It is diagnosed radiologically on high
      resolution computed tomography chest scan by bronchial dilatation (wider than the
      accompanying artery). The causes of bronchiectasis are diverse and include
      previous respiratory tract infections, chronic obstructive pulmonary disease,
      asthma, immunodeficiency and connective tissue diseases. A large proportion of
      cases are idiopathic, reflecting our incomplete understanding of disease
      pathogenesis. Progress in the evidence base is reflected in the 2017 European
      management guidelines and the 2015 update to the Australian guidelines. Effective
      airway clearance remains the cornerstone of bronchiectasis management. This
      should be personalised and reviewed regularly by a respiratory physiotherapist.
      There is now robust evidence for the long term use of oral macrolide antibiotics
      in selected patients to reduce exacerbation frequency. The routine use of long
      term inhaled corticosteroids and/or long-acting bronchodilators should be
      avoided, unless concomitant chronic obstructive pulmonary disease or asthma
      exists. The evidence for nebulised agents including hypertonic saline, mannitol
      and antibiotics is evolving; however, access is challenging outside tertiary
      clinics, and nebulising equipment is required. Smokers should be supported to
      quit. All patients should receive influenza and pneumococcal vaccination.
      Patients with impaired exercise capacity should attend pulmonary rehabilitation.
      There is an important minority of patients for whom aetiology-specific treatment
      exists. The prevalence of bronchiectasis is increasing worldwide; however, the
      burden of disease within Australia is not well defined. To this end, the
      Australian Bronchiectasis Registry began recruitment in 2016 and is interoperable
      with the European and United States bronchiectasis registries to enable
      collaborative research. The recent addition of a bronchiectasis diagnosis-related
      group to the Australian Refined Diagnostic Related Group classification system
      will allow definition of the disease burden within the Australian hospital
      system.

PMID- 30107773
TI  - Potential solutions to improve the governance of multicentre health services
      research.

PMID- 30107774
TI  - The efficacy of medical student selection tools in Australia and New Zealand.

PMID- 30107775
TI  - An era of untreatable gonorrhoea?

PMID- 30107776
TI  - Bond Uni adds EI to medical student selections.

PMID- 30107777
TI  - BALCONY: an R package for MSA and functional compartments of protein variability
      analysis.
AB  - BACKGROUND: Here, we present an R package for entropy/variability analysis that
      facilitates prompt and convenient data extraction, manipulation and visualization
      of protein features from multiple sequence alignments. BALCONY can work with
      residues dispersed across a protein sequence and map them on the corresponding
      alignment of homologous protein sequences. Additionally, it provides several
      entropy and variability scores that indicate the conservation of each residue.
      RESULTS: Our package allows the user to visualize evolutionary variability by
      locating the positions most likely to vary and to assess mutation candidates in
      protein engineering. CONCLUSION: In comparison to other R packages BALCONY allows
      conservation/variability analysis in context of protein structure with linkage of
      the appropriate metrics with physicochemical features of user choice.
      AVAILABILITY: CRAN project page: https://cran.r-project.org/package=BALCONY and
      our website: http://www.tunnelinggroup.pl/software/ for major platforms:
      Linux/Unix, Windows and Mac OS X.

PMID- 30107778
TI  - Real-time monitoring of Pseudomonas aeruginosa biofilm formation on endotracheal
      tubes in vitro.
AB  - BACKGROUND: Pseudomonas aeruginosa is an opportunistic bacterial pathogen
      responsible for both acute and chronic infections in humans. In particular, its
      ability to form biofilm, on biotic and abiotic surfaces, makes it particularly
      resistant to host's immune defenses and current antibiotic therapies as well.
      Innovative antimicrobial materials, like hydrogel, silver salts or nanoparticles
      have been used to cover new generation catheters with promising results.
      Nevertheless, biofilm remains a major health problem. For instance, biofilm
      produced onto endotracheal tubes (ETT) of ventilated patients plays a relevant
      role in the onset of ventilation-associated pneumonia. Most of our knowledge on
      Pseudomonas aeruginosa biofilm derives from in vitro studies carried out on
      abiotic surfaces, such as polystyrene microplates or plastic materials used for
      ETT manufacturing. However, these approaches often provide underestimated results
      since other parameters, in addition to bacterial features (i.e. shape and
      material composition of ETT) might strongly influence biofilm formation. RESULTS:
      We used an already established biofilm development assay on medically-relevant
      foreign devices (CVC catheters) by a stably transformed bioluminescent (BLI)
      Pseudomonas aeruginosa strain, in order to follow up biofilm formation on ETT by
      bioluminescence detection. Our results demonstrated that it is possible: i) to
      monitor BLI-Pseudomonas aeruginosa biofilm development on ETT pieces in real
      time, ii) to evaluate the three-dimensional structure of biofilm directly on ETT,
      iii) to assess metabolic behavior and the production of microbial virulence
      traits of bacteria embedded on ETT-biofilm. CONCLUSIONS: Overall, we were able to
      standardize a rapid and easy-to-perform in vitro model for real-time monitoring
      Pseudomonas aeruginosa biofilm formation directly onto ETT pieces, taking into
      account not only microbial factors, but also ETT shape and material. Our study
      provides a rapid method for future screening and validation of novel
      antimicrobial drugs as well as for the evaluation of novel biomaterials employed
      in the production of new classes of ETT.

PMID- 30107779
TI  - Synchronous birth is a dominant pattern in receptor-ligand evolution.
AB  - BACKGROUND: Interactions between proteins are key components in the chemical and
      physical processes of living organisms. Among these interactions, membrane
      receptors and their ligands are particularly important because they are at the
      interface between extracellular and intracellular environments. Many studies have
      investigated how binding partners have co-evolved in genomes during the
      evolution. However, little is known about the establishment of the interaction on
      a phylogenetic scale. In this study, we systematically studied the time of birth
      of genes encoding human membrane receptors and their ligands in the animal tree
      of life. We examined a total of 553 pairs of ligands/receptors, representing non
      redundant interactions. RESULTS: We found that 41% of the receptors and their
      respective first ligands appeared in the same branch, representing 2.5-fold more
      than expected by chance, thus suggesting an evolutionary dynamic of
      interdependence and conservation between these partners. In contrast, 21% of the
      receptors appeared after their ligand, i.e. three-fold less often than expected
      by chance. Most surprisingly, 38% of the receptors appeared before their first
      ligand, as much as expected by chance. CONCLUSIONS: According to these results,
      we propose that a selective pressure is exerted on ligands and receptors once
      they appear, that would remove molecules whose partner does not appear quickly.

PMID- 30107780
TI  - The complete mitochondrial genome of the early flowering plant Nymphaea colorata
      is highly repetitive with low recombination.
AB  - BACKGROUND: Mitochondrial genomes of flowering plants (angiosperms) are highly
      dynamic in genome structure. The mitogenome of the earliest angiosperm Amborella
      is remarkable in carrying rampant foreign DNAs, in contrast to Liriodendron, the
      other only known early angiosperm mitogenome that is described as 'fossilized'.
      The distinctive features observed in the two early flowering plant mitogenomes
      add to the current confusions of what early flowering plants look like. Expanded
      sampling would provide more details in understanding the mitogenomic evolution of
      early angiosperms. Here we report the complete mitochondrial genome of water lily
      Nymphaea colorata from Nymphaeales, one of the three orders of the earliest
      angiosperms. RESULTS: Assembly of data from Pac-Bio long-read sequencing yielded
      a circular mitochondria chromosome of 617,195 bp with an average depth of 601*.
      The genome encoded 41 protein coding genes, 20 tRNA and three rRNA genes with 25
      group II introns disrupting 10 protein coding genes. Nearly half of the genome is
      composed of repeated sequences, which contributed substantially to the intron
      size expansion, making the gross intron length of the Nymphaea mitochondrial
      genome one of the longest among angiosperms, including an 11.4-Kb intron in cox2,
      which is the longest organellar intron reported to date in plants. Nevertheless,
      repeat mediated homologous recombination is unexpectedly low in Nymphaea
      evidenced by 74 recombined reads detected from ten recombinationally active
      repeat pairs among 886,982 repeat pairs examined. Extensive gene order changes
      were detected in the three early angiosperm mitogenomes, i.e. 38 or 44 events of
      inversions and translocations are needed to reconcile the mitogenome of Nymphaea
      with Amborella or Liriodendron, respectively. In contrast to Amborella with six
      genome equivalents of foreign mitochondrial DNA, not a single horizontal gene
      transfer event was observed in the Nymphaea mitogenome. CONCLUSIONS: The Nymphaea
      mitogenome resembles the other available early angiosperm mitogenomes by a
      similarly rich 64-coding gene set, and many conserved gene clusters, whereas
      stands out by its highly repetitive nature and resultant remarkable intron
      expansions. The low recombination level in Nymphaea provides evidence for the
      predominant master conformation in vivo with a highly substoichiometric set of
      rearranged molecules.

PMID- 30107781
TI  - High-density genetic map construction and quantitative trait loci analysis of the
      stony hard phenotype in peach based on restriction-site associated DNA
      sequencing.
AB  - BACKGROUND: Peach (Prunus persica) is an important fruit crop that generally
      softens rapidly after harvest resulting in a short shelf-life. By contrast, stony
      hard (SH) peach fruit does not soften and hardly produces ethylene. To explore
      the candidate genes responsible for the SH phenotype, a high-density genetic map
      was constructed by restriction-site associated DNA sequencing technology.
      RESULTS: In the present study, the linkage map consisted of 1310 single
      nucleotide polymorphism markers, spanning 454.2 cM, with an average marker
      distance of 0.347 cM. The single nucleotide polymorphisms were able to anchor
      eight linkage groups to their corresponding chromosomes. Based on this high
      density integrated peach linkage map and two years of fruit phenotyping, two
      potential quantitative trait loci for the SH trait were identified and positioned
      on the genetic map. Additionally, Prupe.6G150900.1, a key gene in abscisic acid
      (ABA) biosynthesis, displayed a differential expression profile identical to the
      ABA accumulation pattern: mRNA transcripts were maintained at a high level during
      storage of SH peaches but occurred at low levels in melting fruit. CONCLUSION:
      Thus Prupe.6G150900.1 might play a crucial role in the SH phenotype of peach in
      which ABA negatively regulates ethylene production. Also, this high-density
      linkage map of peach will contribute to the mapping of important fruit traits and
      quantitative trait loci identification.

PMID- 30107782
TI  - Identification and characterization of miRNAs in the gills of the mud crab
      (Scylla paramamosain) in response to a sudden drop in salinity.
AB  - BACKGROUND: The mud crab (Scylla paramamosain) is a euryhaline and commercially
      important species. MiRNAs participate in the regulation of many physiological
      activities. RESULTS: The miRNA transcriptome of the gills of S. paramamosain was
      used to investigate the expression profiles of miRNAs in response to a sudden
      drop in salinity. In total, seven known miRNAs and 43 novel miRNAs were
      identified, with 18 differentially expressed small RNAs. Fourteen thousand nine
      hundred fifty-one differentially expressed miRNAs target genes were screened by
      prediction. GO analysis of differentially expressed miRNAs target genes indicated
      that 578 genes associated with cellular processes, 523 associated with metabolic
      processes, and 422 associated with single-organism processes were the most
      strongly affected by a sudden drop in salinity from 230/00 to 30/00. KEGG pathway
      analysis showed 14 pathways were related to amino acid metabolism, which plays an
      important role in osmoregulation. Besides, several pathways were associated with
      starch and sucrose metabolism (ko00500), glycosaminoglycan degradation (ko00531),
      and galactose metabolism (ko00052). CONCLUSIONS: S. paramamosain regulated
      osmotic pressure and energy balance by regulating target genes to adapt to a
      sudden changes in salinity. These results provided a basis for further
      investigations of miRNA-modulating networks underlying the osmoregulation of S.
      paramamosain.

PMID- 30107783
TI  - In-solution Y-chromosome capture-enrichment on ancient DNA libraries.
AB  - BACKGROUND: As most ancient biological samples have low levels of endogenous DNA,
      it is advantageous to enrich for specific genomic regions prior to sequencing.
      One approach-in-solution capture-enrichment-retrieves sequences of interest and
      reduces the fraction of microbial DNA. In this work, we implement a capture
      enrichment approach targeting informative regions of the Y chromosome in six
      human archaeological remains excavated in the Caribbean and dated between 200 and
      3000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone,
      whole-genome capture followed by YCC (WGC + YCC) versus non-enriched (pre
      capture) libraries. RESULTS: The six samples show different levels of initial
      endogenous content, with very low (< 0.05%, 4 samples) or low (0.1-1.54%, 2
      samples) percentages of sequenced reads mapping to the human genome. We recover
      12-9549 times more targeted unique Y-chromosome sequences after capture, where
      0.0-6.2% (WGC + YCC) and 0.0-23.5% (YCC) of the sequence reads were on-target,
      compared to 0.0-0.00003% pre-capture. In samples with endogenous DNA content
      greater than 0.1%, we found that WGC followed by YCC (WGC + YCC) yields lower
      enrichment due to the loss of complexity in consecutive capture experiments,
      whereas in samples with lower endogenous content, the libraries' initial low
      complexity leads to minor proportions of Y-chromosome reads. Finally, increasing
      recovery of informative sites enabled us to assign Y-chromosome haplogroups to
      some of the archeological remains and gain insights about their paternal lineages
      and origins. CONCLUSIONS: We present to our knowledge the first in-solution
      capture-enrichment method targeting the human Y-chromosome in aDNA sequencing
      libraries. YCC and WGC + YCC enrichments lead to an increase in the amount of Y
      DNA sequences, as compared to libraries not enriched for the Y-chromosome. Our
      probe design effectively recovers regions of the Y-chromosome bearing
      phylogenetically informative sites, allowing us to identify paternal lineages
      with less sequencing than needed for pre-capture libraries. Finally, we recommend
      considering the endogenous content in the experimental design and avoiding
      consecutive rounds of capture, as clonality increases considerably with each
      round.

PMID- 30107784
TI  - Iron-dependent essential genes in Salmonella Typhimurium.
AB  - BACKGROUND: The molecular mechanisms underlying bacterial cell death due to
      stresses or bactericidal antibiotics are complex and remain puzzling. Due to the
      current crisis of antibiotic resistance, development of effective antibiotics is
      urgently required. Previously, it has been shown that iron is required for
      effective killing of bacterial cells by numerous bactericidal antibiotics.
      RESULTS: We investigated the death or growth inhibition of S. Typhimurium under
      iron-restricted conditions, following disruption of essential genes, by
      transposon mutagenesis using transposon sequencing (Tn-seq). Our high-resolution
      Tn-seq analysis revealed that transposon mutants of S. Typhimurium with
      insertions in essential genes escaped immediate killing or growth inhibition
      under iron-restricted conditions for approximately one-third of all previously
      known essential genes. Based on this result, we classified all essential genes
      into two categories, iron-dependent essential genes, for which the insertion
      mutants can grow slowly if iron is restricted, and iron-independent essential
      genes, for which the mutants become nonviable regardless of iron concentration.
      The iron-dependency of the iron-dependent essential genes was further validated
      by the fact that the relative abundance of these essential gene mutants increased
      further with more severe iron restrictions. Our unexpected observation can be
      explained well by the common killing mechanisms of bactericidal antibiotics via
      production of reactive oxygen species (ROS). In this model, iron restriction
      would inhibit production of ROS, leading to reduced killing activity following
      blocking of essential gene functions. Interestingly, the targets of most
      antibiotics currently in use clinically are iron-dependent essential genes.
      CONCLUSIONS: Our result suggests that targeting iron-independent essential genes
      may be a better strategy for future antibiotic development, because blocking
      their essential gene functions would lead to immediate cell death regardless of
      the iron concentration. This work expands our knowledge on the role of iron to a
      broad range of essential functions and pathways, providing novel insights for
      development of more effective antibiotics.

PMID- 30107785
TI  - Identifying mixed Mycobacterium tuberculosis infections from whole genome
      sequence data.
AB  - BACKGROUND: Mixed, polyclonal Mycobacterium tuberculosis infection occurs in
      natural populations. Developing an effective method for detecting such cases is
      important in measuring the success of treatment and reconstruction of
      transmission between patients. Using whole genome sequence (WGS) data, we assess
      two methods for detecting mixed infection: (i) a combination of the number of
      heterozygous sites and the proportion of heterozygous sites to total SNPs, and
      (ii) Bayesian model-based clustering of allele frequencies from sequencing reads
      at heterozygous sites. RESULTS: In silico and in vitro artificially mixed and
      known pure M. tuberculosis samples were analysed to determine the specificity and
      sensitivity of each method. We found that both approaches were effective in
      distinguishing between pure strains and mixed infection where there was
      relatively high (> 10%) proportion of a minor strain in the mixture. A large
      dataset of clinical isolates (n = 1963) from the Karonga Prevention Study in
      Northern Malawi was tested to examine correlations with patient characteristics
      and outcomes with mixed infection. The frequency of mixed infection in the
      population was found to be around 10%, with an association with year of
      diagnosis, but no association with age, sex, HIV status or previous tuberculosis.
      CONCLUSIONS: Mixed Mycobacterium tuberculosis infection was identified in silico
      using whole genome sequence data. The methods presented here can be applied to
      population-wide analyses of tuberculosis to estimate the frequency of mixed
      infection, and to identify individual cases of mixed infections. These cases are
      important when considering the evolution and transmission of the disease, and in
      patient treatment.

PMID- 30107786
TI  - Role of elevated red cell distribution width on acute kidney injury patients
      after cardiac surgery.
AB  - BACKGROUND: The aim of the study was to explore associations between elevated red
      cell distribution width (RDW) and acute kidney injury (AKI) in patients
      undergoing cardiac surgery (CS-AKI). METHODS: Preoperative, intraoperative and
      postoperative data of 10,274 patients undergoing cardiac surgery, including
      demographic data, were prospectively collected from January 2009 to December
      2014. Propensity score matching was used on the basis of clinical characteristics
      and preoperative variables. An elevated RDW was defined as the difference between
      RDW 24 h after cardiac surgery and the latest RDW before cardiac surgery.
      RESULTS: A total of 10,274 patients were included in the unmatched cohort, and
      3146 patients in the propensity-matched cohort. In the unmatched cohort, the
      overall CS-AKI incidence was 32.8% (n = 3365) with a hospital mortality of 5.5%
      (n = 185). In the propensity-matched cohort, the elevated RDW in AKI patients was
      higher than in patients without AKI (0.3% (0.0%, 0.7%) vs 0.5% (0.1, 1.1%), P < 
      0.001) and the elevated RDW incidences were 0.4% (0.1%, 0.9%), 0.6% (0.2%, 1.1%)
      and 1.1% (0.3%, 2.1%) in stage 1, 2 and 3 AKI patients (P <  0.001). Among
      propensity-matched patients with CS-AKI, the level of elevated RDW in non
      survivors was higher than in survivors [1.2% (0.5%, 2.3%) vs 0.5% (0.1%, 1.0%), P
      <  0.001] and a 0.1% increase in elevated RDW was associated with a 0.24% higher
      risk of within-hospital mortality in patients with CS-AKI. Estimating the
      receiver-operating characteristic (ROC) area under the curve (AUC) showed that an
      elevated RDW had moderate discriminative power for AKI development (AUC = 0.605,
      95% CI, 0.586-0.625; P <  0.001) and hospital mortality (AUC = 0.716, 95% CI,
      0.640-0.764; P <  0.001) in the propensity-matched cohort. CONCLUSIONS: An
      elevated RDW might be an independent prognostic factor for the severity and poor
      prognosis of CS-AKI.

PMID- 30107787
TI  - A digitally supported home-based exercise training program and dietary protein
      intervention for community dwelling older adults: protocol of the cluster
      randomised controlled VITAMIN trial.
AB  - BACKGROUND: Increased physical activity and dietary protein intake are promising
      interventions to prevent or treat the age-related decline in physical performance
      in older adults. There are well-controlled exercise as well as dietary
      intervention studies that show beneficial effects on physical performance in
      older adults. In practice, however, weekly group based exercise or nutritional
      programs may not be as effective. To optimise these exercise programs for
      community dwelling older adults, a digitally supported and personalised home
      based exercise training program has been designed aiming to improve physical
      performance in older adults. In addition, a protein intervention in combination
      with the training program may further improve physical performance in older
      adults. METHODS: The VITAMIN study will be a cluster randomised controlled trial
      with three parallel arms. In total, 240 community dwelling older adults (>= 55
      years) participating in weekly group exercise are randomly allocated into: 1)
      regular weekly exercise program (Control group, n = 80), 2) digitally supported
      personalised home-based exercise training program group (VITA group, n = 80) and
      3) digitally supported personalised home-based exercise training program group
      plus dietary protein counselling (VITA-Pro group, n = 80). The VITAMIN study aims
      to evaluate effectiveness of the digitally supported personalised home-based
      exercise training program as well as the additional value of dietary protein on
      physical performance after 6 months. In addition, a 12 month follow-up
      measurement will assess the retaining effect of the interventions. Primary
      outcome is physical performance measured by the Modified Physical Performance
      Test (M-PPT) and relevant secondary and observational outcomes include habitual
      physical activity and dietary intake, body composition, cognitive performance,
      quality of life, compliance and tablet usage. Data will be analysed by Linear
      Mixed Models. DISCUSSION: To our knowledge, the VITAMIN study is the first study
      that investigates the impact of home-based exercise, protein intake as well as
      use of persuasive technology in the population of community dwelling older
      adults. TRIAL REGISTRATION: NL56094.029.16 / NTR ( TC = 5888 ; registered 03-06
      2016).

PMID- 30107789
TI  - Passive exercise to improve quality of life, activities of daily living, care
      burden and cognitive functioning in institutionalized older adults with dementia 
      a randomized controlled trial study protocol.
AB  - BACKGROUND: Dementia affects cognitive functioning, physical functioning,
      activities of daily living (ADLs), and quality of life (QOL). Pharmacological
      treatments to manage, cure or prevent dementia remain controversial. Therefore
      development of non-pharmacological approaches to prevent, or at least delay the
      onset and progression of dementia is urgently needed. Passive exercise is
      proposed to be such a non-pharmacological alternative. This study primarily aims
      to investigate the effects of three different forms of passive exercise on QOL
      and ADLs of institutionalized patients with dementia. The secondary aims are to
      assess the effects of three different forms of passive exercise on cognitive
      functioning and physical functioning of institutionalized patients with dementia
      as well as on care burden of both the primary formal and primary informal
      caregivers of these patients. METHODS: This is a multicenter randomized
      controlled trial. Three forms of passive exercise are distinguished; motion
      simulation (MSim), whole body vibration (WBV), and a combination of both MSim +
      WBV. Intervention effects are compared to a control group receiving regular care.
      Institutionalized patients with dementia follow a six-week intervention program
      consisting of four 4-12 min sessions a week. The primary outcome measures QOL and
      ADLs and secondary outcome measure care burden are assessed with questionnaires
      filled in by the primary formal and informal caregivers of the patient. The other
      secondary outcome measures cognitive and physical functioning are assessed by
      individual testing. The four groups are compared at baseline, after 6 weeks of
      intervention, and 2 weeks after the intervention has ended. DISCUSSION: This
      study will provide insight in the effects of different forms of passive exercise
      on QOL, ADLs, cognitive and physical functioning and care burden of
      institutionalized patients with dementia and their primary formal and informal
      caregivers. The results of this study might support the idea that passive
      exercise can be an efficient alternative for physical activity for patients not
      able to be or stay involved in active physical exercise. TRIAL REGISTRATION: The
      Netherlands National Trial Register ( NTR6290 ). Retrospectively registered 29
      March 2017.

PMID- 30107790
TI  - Correlates of sexual inactivity and met need for contraceptives among young women
      in Ghana.
AB  - BACKGROUND: Young women in sub-Saharan Africa continue to experience unintended
      pregnancies despite effective contraceptive methods being more readily available
      than ever. This study sought to determine the correlates of met need for
      contraceptives and sexual inactivity among young women in Ghana who want to
      postpone childbearing. We examine this among all women and then separately by
      marital status. METHODS: Using data from 1532 females aged 15-24 years from the
      2014 Ghana Demographic and Health Survey, we conducted descriptive and
      multinomial logistic regression analyses to assess sociodemographic, economic and
      obstetric determinants of the type of family planning method (current abstinence,
      modern contraceptive method) used by married and unmarried young women. RESULTS:
      A higher proportion (~ 44%) of the respondents was currently abstinent compared
      to those with met need (~ 25%). Abstinence was higher among single young women
      while unmet and met need were higher among the married. Having at least senior
      high school education was significantly associated with the likelihood of current
      abstinence (especially among single women) and with met need. Being in the middle
      and rich categories, on the other hand, was associated with lower likelihood of
      current abstinence and a met need. Compared with multiparous women, those with
      one or no surviving child had a lower likelihood of being abstinent and having a
      met need. Other correlates of both current abstinence and met need are region of
      residence and ethnicity, while previous pregnancy termination and age were
      associated with abstinence and contraceptive use, respectively. CONCLUSIONS:
      Unmet need is high among young women but abstinence is an option they are using.
      As reproductive health programmes target the at-risk groups, the secondary and
      higher educational levels must be attained by most women as this is associated
      with use of abstinence and met need.

PMID- 30107788
TI  - Defining the process to literature searching in systematic reviews: a literature
      review of guidance and supporting studies.
AB  - BACKGROUND: Systematic literature searching is recognised as a critical component
      of the systematic review process. It involves a systematic search for studies and
      aims for a transparent report of study identification, leaving readers clear
      about what was done to identify studies, and how the findings of the review are
      situated in the relevant evidence. Information specialists and review teams
      appear to work from a shared and tacit model of the literature search process.
      How this tacit model has developed and evolved is unclear, and it has not been
      explicitly examined before. The purpose of this review is to determine if a
      shared model of the literature searching process can be detected across
      systematic review guidance documents and, if so, how this process is reported in
      the guidance and supported by published studies. METHOD: A literature review. Two
      types of literature were reviewed: guidance and published studies. Nine guidance
      documents were identified, including: The Cochrane and Campbell Handbooks.
      Published studies were identified through 'pearl growing', citation chasing, a
      search of PubMed using the systematic review methods filter, and the authors'
      topic knowledge. The relevant sections within each guidance document were then
      read and re-read, with the aim of determining key methodological stages.
      Methodological stages were identified and defined. This data was reviewed to
      identify agreements and areas of unique guidance between guidance documents.
      Consensus across multiple guidance documents was used to inform selection of 'key
      stages' in the process of literature searching. RESULTS: Eight key stages were
      determined relating specifically to literature searching in systematic reviews.
      They were: who should literature search, aims and purpose of literature
      searching, preparation, the search strategy, searching databases, supplementary
      searching, managing references and reporting the search process. CONCLUSIONS:
      Eight key stages to the process of literature searching in systematic reviews
      were identified. These key stages are consistently reported in the nine guidance
      documents, suggesting consensus on the key stages of literature searching, and
      therefore the process of literature searching as a whole, in systematic reviews.
      Further research to determine the suitability of using the same process of
      literature searching for all types of systematic review is indicated.

PMID- 30107791
TI  - C-reactive protein and procalcitonin to discriminate between tuberculosis,
      Pneumocystis jirovecii pneumonia, and bacterial pneumonia in HIV-infected
      inpatients meeting WHO criteria for seriously ill: a prospective cohort study.
AB  - BACKGROUND: Tuberculosis, bacterial community-acquired pneumonia (CAP), and
      Pneumocystis jirovecii pneumonia (PJP) are the three commonest causes of
      hospitalisation in HIV-infected adults. Prompt diagnosis and treatment initiation
      are important to reduce morbidity and mortality, but are hampered by limited
      diagnostic resources in resource poor settings. C-reactive protein (CRP) and
      procalcitonin have shown diagnostic utility for respiratory tract infections,
      however few studies have focussed on their ability to distinguish between
      tuberculosis, CAP, and PJP in HIV-infected inpatients. METHODS: We evaluated the
      diagnostic accuracy of CRP and procalcitonin, compared with composite reference
      standards, to discriminate between the three target infections in adult HIV
      infected inpatients in two district level hospitals in Cape Town, South Africa.
      Participants were admitted with current cough and danger signs in accordance with
      the WHO algorithm for tuberculosis in seriously ill HIV-infected patients. Study
      clinicians were blinded to CRP and procalcitonin results. RESULTS: Two hundred
      forty-eight participants met study case definitions: 133 with tuberculosis, 61
      with CAP, 16 with PJP, and 38 with mixed infection. In the 210 particpants with
      single infections the differences in median CRP and procalcitonin concentrations
      between the three infections were statistically significant, but distributions
      overlapped considerably. CRP and procalcitonin concentrations were highest in the
      CAP group and lowest in the PJP group. CRP and procalcitonin cut-offs with
      sensitivities of >=90% were found for all three target infection pairs, but
      corresponding specificities were low. Highest receiver operating characteristic
      areas under the curve for CRP and procalcitonin were for PJP versus tuberculosis
      and PJP versus CAP (0.68 and 0.71, and 0.74 and 0.69 respectively). CONCLUSIONS:
      CRP and procalcitonin showed limited value in discriminating between the three
      target infections due to widely overlapping distributions, but diagnostic
      accuracy was higher for discriminating PJP from CAP or tuberculosis. Our findings
      show limitations for CRP and procalcitonin, particularly for discriminiation of
      tuberculosis form CAP, however they may have greater diagnostic utility as part
      of a panel of biomarkers or in clinical prediction rules.

PMID- 30107792
TI  - Estimation of variance components and prediction of breeding values based on
      group records from varying group sizes.
AB  - BACKGROUND: Records on groups of individuals rather than on single individuals
      could be valuable for predicting breeding values (BV) of the traits that are
      difficult or costly to measure individually, such as feed intake in pigs or beef
      cattle. Here, we present a model, which handles group records from varying group
      sizes and involves multiple fixed and random effects, for estimating variance
      components and predicting BV. Moreover, using simulation, we investigated the
      efficiency of group records for predicting BV in situations with various group
      sizes and structures, and factors that affect the trait. RESULTS: The results
      show that the presented model for group records worked well and that variances
      estimated from group records with varying group sizes were consistent with those
      estimated from individual records, but with larger standard errors. Ignoring
      litter and pen effects had very little or no influence on the accuracy of
      estimated BV (EBV) obtained from group records. However, ignoring litter effects
      resulted in biased estimates of additive genetic variance and EBV. The presence
      of litter and pen effects on phenotypes decreased the accuracy of EBV although
      the prediction model fitted both effects. Having more littermates in the same pen
      led to a higher accuracy of EBV. The decay of EBV accuracy with increasing group
      size was more marked for scenarios with litter and pen effects than without. When
      litters of six individuals were divided into two pens, accuracies of EBV obtained
      from group records with a size up to 12 (average 9.6) and up to 24 (average 19.2)
      were 66.6 and 57.6% of those estimated from individual records in the scenario
      with litter and pen effects on phenotypes. These percentages reached 77.0 and
      68.4% in the scenario without litter and pen effects on phenotypes. CONCLUSIONS:
      Our results indicate that the model works appropriately for the analysis of group
      records from varying group sizes. Using group records for genetic evaluation of
      traits such as feed intake in pig is feasible and the efficiency of the resulting
      estimates depends on the size and structure of the groups and on the magnitude of
      the variances for litter and pen effects.

PMID- 30107793
TI  - Prevalence of domestic violence and associated factors among pregnant women
      attending antenatal care service at University of Gondar Referral Hospital,
      Northwest Ethiopia.
AB  - BACKGROUND: Domestic violence during pregnancy with its many negative fetal and
      maternal outcomes is a common public health problem all over the world.
      Nonetheless, the problem is not well investigated and understood in Ethiopia.
      Hence, this study aimed to assess the prevalence of domestic violence and
      associated factors among pregnant women attending the University of Gondar
      Referral Hospital antenatal care (ANC) services. METHODS: A hospital-based cross
      sectional study was conducted from March-May 2016. A total of 450 pregnant women
      who visited the clinic were included in the study. A systematic random sampling
      technique was used to select study participants, and a pretested structured
      questionnaire was employed to collect data. The WHO multi-country study on
      women's health and domestic violence against women was used to assess the
      violence against pregnant women. Descriptive statistics such as means,
      frequencies and percentages were computed. A multivariable logistic regression
      analysis was carried out to identify factors associated with domestic violence,
      and variables with p-values < 0.05 were considered as statistically significant.
      RESULTS: Of the total pregnant women surveyed, 58.7% were victims of at least one
      form of domestic violence during pregnancy, emotional violence being the most
      common (57.8%). The multivariable logistic regression analysis showed that house
      wives (adjusted odd ratio (AOR) = 3.43, 95% CI: 1.63, 7.21), women with no salary
      of their own (AOR = 3.37, 95% CI: 2.14, 7.95), partners' daily use of alcohol
      (AOR = 4.59, 95%CI: 1.82, 11.56), women who believed in women's rights to decide
      to be pregnant (AOR = 1.77, 95%CI: 1.18, 2.89), and women who disobeyed their
      partner (AOR = 2.36, 95%CI: 1.37, 4.07) were found to be positively and
      significantly associated with domestic violence during pregnancy. CONCLUSION: A
      high proportion of pregnant women experienced domestic violence during their
      pregnancy. Being a housewife, poor income status, partners' use of alcohol,
      unwanted pregnancy, and disobeying of the women to their partner were factors
      associated with domestic violence during pregnancy. Evidence based female
      empowerment, especially the empowerment of women without income of their own,
      partner education and positive relations between partners are very important to
      minimize the problem.

PMID- 30107794
TI  - Biodegradable polymer drug-eluting stents versus second-generation drug-eluting
      stents in patients with and without diabetes mellitus: a single-center study.
AB  - BACKGROUND: To improve outcomes in patients with diabetes mellitus (DM)
      undergoing percutaneous coronary intervention remain an unmet clinical need. The
      study aimed to evaluate the efficacy and safety of G2-DESs and BP-DESs in
      patients with and without DM in a single center in China. METHODS: A total of
      7666 consecutive patients who exclusively had G2-DES or BP-DES implantation
      throughout 2013 in our center were studied. The primary efficacy endpoint was any
      target lesion revascularization (TLR), whereas the primary safety endpoint was a
      composite of death or myocardial infarction (MI) at 2-year follow-up. RESULTS: G2
      DESs had a similar occurrence of death, non-fatal MI, TLR, stroke, and stent
      thrombosis compared with BP-DESs in patients with DM (all P > 0.05). The
      incidence of TVR and TLR was lower for G2-DESs than for BP-DESs in patients
      without DM (3.2% vs. 5.1%, P = 0.002; 2.2% vs. 4.5%, P < 0.001, respectively).
      Kaplan-Meier analysis also showed better TVR- and TLR-free survival rates for G2
      DESs than for BP-DESs in patients without DM. Multivariate analysis showed that a
      BP-DES was an independent risk factor for TLR (hazard ratio 1.963, 95% confidence
      interval 1.390-2.772, P < 0.001) in patients without DM, which was not predictive
      of other components of major adverse cardiac events (P > 0.05). CONCLUSIONS: G2
      DESs have better efficacy, represented by a reduced risk of TLR, and similar
      safety compared with BP-DESs in patients without DM. G2-DESs have similar
      efficacy and safety compared with BP-DESs in patients with DM at 2-year follow
      up.

PMID- 30107796
TI  - Implementing and evaluating a primary care service for oral surgery: a case
      study.
AB  - BACKGROUND: A primary care oral surgery service was commissioned alongside an
      electronic referral management system in England, in response to rising demand
      for Oral Surgery services in secondary care. It is important to ensure that
      standards of quality and safety are similar to those in existing secondary care
      services, and that the new service is acceptable to stakeholders. The aim of this
      study is therefore to conduct an in depth case study to explore safety, quality,
      acceptability and implementation of the new service. METHODS: This case study
      draws on multiple sources of evidence to report on the commissioning process,
      implementation, treatment outcomes and acceptability to patients relating to a
      new oral surgery service in a primary care setting. A combination of audit data
      and interviews were analysed. RESULTS: Most referrals to the new service
      consisted of tooth extractions of appropriate complexity for the service. There
      were issues with lack of awareness of the new service in a primary care setting
      within referring primary care practices and patients at the start of
      implementation, however over time the service became a fully integrated part of
      the service landscape. Complications reported following surgery were low.
      CONCLUSION: Patients liked the convenience of the new service in terms of shorter
      waiting time and geographical location and their patient reported experience
      measures and outcomes were similar to those reported in secondary care. Providing
      appropriate clinical governance was in place, oral surgery could safely be
      provided in a primary care setting for patients without complex medical needs.
      Attention needs to be paid to communication with general dental practices around
      changes to the service pathway during the early implementation period to ensure
      all patients can receive care in the most appropriate setting.

PMID- 30107797
TI  - Frequency of use of the religious exemption in New Jersey cases of determination
      of brain death.
AB  - BACKGROUND: The 1981 Uniform Determination of Death Act (UDDA) established the
      validity of both cardio-respiratory and neurological criteria of death. However,
      many religious traditions including most forms of Haredi Judaism (ultra-orthodox)
      and many varieties of Buddhism strongly disagree with death by neurological
      criteria (DNC). Only one state in the U.S., New Jersey, allows for both religious
      exemptions to DNC and provides continuation of health insurance coverage when an
      exception is invoked in its 1991 Declaration of Death Act (NJDDA). There is yet
      no quantitative or qualitative data on the frequencies of religious exemptions in
      New Jersey. This study gathered information about the frequency of religious
      exemptions and policy in New Jersey that was created out of respect for religious
      beliefs. METHODS: Literature and internet searches on topics related to religious
      objections to DNC were conducted. Fifty-three chaplains and heads of bioethics
      committees in New Jersey hospitals were contacted by phone or email requesting a
      research interview. Respondents answered a set of questions about religious
      exemptions to DNC at the hospital where they worked that explored the frequency
      of such religious exemptions in the past five years, the religious tradition
      indicated, and whether any request for a religious exemption had been denied.
      This study was approved by the Northeastern University Institutional Review Board
      (IRB #: 16-03-15). RESULTS: Eighteen chaplains and bioethics committee members
      participated in a full research interview. Of these, five reported instances of
      religious exemptions to DNC occurring at the hospital at which they worked for a
      total of approximately 30-36 known exemptions in the past five years. Families
      sought religious exemptions because of faith in an Orthodox Judaism tradition and
      nonreligious reasons. No failed attempts to obtain an exemption were reported.
      CONCLUSIONS: Religious exemptions to DNC in New Jersey do occur, although very
      infrequently. Prior to this study, there was no information on their frequency.
      Considering religious exemptions do occur, there is a need for national or state
      policies that addresses both religious objections to DNC and hospital resources.
      More information is needed to better understand the impact of granting religious
      exemptions before new policy can be established.

PMID- 30107795
TI  - The impact of rural outreach programs on medical students' future rural
      intentions and working locations: a systematic review.
AB  - BACKGROUND: Significant investment has been undertaken by many countries into
      'Rural Clinical Training Placement Schemes' for medical students in order to deal
      with shortages of trained health care professionals in rural and remote
      locations. This systematic review examines the evidence base of rural educational
      programs within medical education and focusses on workforce intentions and
      employment outcomes. The study provides a detailed description of the
      methodological characteristics of the literature, thematic workforce outcomes and
      key related factors are identified, study quality is assessed, and the findings
      are compared within an international context. METHODS: A systematic review
      looking at international literature of rural placement programs within medical
      education between January 2005 to January 2017 from databases including; Medline,
      Embase, NursingOVID, PubMed and Cochrane. The study adopted the PRISMA protocol.
      A quality assessment of the literature was conducted based on the Health Gains
      Notation Framework. RESULTS: Sixty two papers met the inclusion criteria. The
      review identified three program classifications; Rural Clinical Placement
      Programs, Rural Clinical Placement Programs combined with a rural health
      educational curriculum component and Rural Clinical School Programs. The studies
      included were from Australia, United States, Canada, New Zealand, Thailand and
      Africa. Questionnaires and tracking or medical registry databases were the most
      commonly reported research tools and the majority were volunteer programs. Most
      studies identified potential rural predictors/confounders, however a number did
      not apply control groups and most programs were based on a single site. There was
      a clear discrepancy in the ideal rural clinical placement length. Outcomes themes
      were identified related to rural workforce outcomes. Most studies reported that
      an organised, well-funded, rural placement or rural clinical school program
      produced positive associations with increased rural intentions and actual
      graduate rural employment. CONCLUSIONS: Future research should focus on large
      scale methodologically rigorous multi-site rural program studies, with
      longitudinal follow up of graduates working locations. Studies should apply pre
      and post-intervention surveys to measure change in attitudes and control for
      predictive confounders, control groups should be applied; and in-depth
      qualitative research should be considered to explore the specific factors of
      programs that are associated with encouraging rural employment.

PMID- 30107798
TI  - Overweight and obesity impair left ventricular systolic function as measured by
      left ventricular ejection fraction and global longitudinal strain.
AB  - AIMS: Obesity is associated with type 2 diabetes mellitus, left ventricular
      diastolic dysfunction and heart failure but it is unclear to which extent it is
      related to left ventricular systolic dysfunction. The aim of the study was to
      explore the effects of overweight and obesity on left ventricular systolic
      function in patients with type 2 diabetes mellitus and a control group of non
      diabetic persons. METHODS: We prospectively investigated 384 patients with type 2
      diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL
      studies. The participants were grouped according to body mass index (normal
      weight < 25 kg/m2, overweight 25-29 kg/m2, and obesity >= 30 kg/m2).
      Echocardiography was performed at the beginning of the study and after 4-years in
      the patient group. RESULTS: Univariable and multivariable regression analysis
      revealed that variations in left ventricular ejection fraction, global
      longitudinal strain, left ventricular mass and diastolic function expressed as
      E/e (the ratio between early diastolic mitral flow and annular motion velocities)
      all are related to body mass index. The mean and standard deviation of left
      ventricular ejection fraction and global longitudinal strain values were 57% (8%)
      vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for
      overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p < 0.05 vs. p < 0.05).
      Corresponding results in the control group were 58% (6%) vs. - 22.3% (3.0%), 55%
      (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p < 0.05 vs. p < 0.05).
      Patients who gained weight from baseline to follow-up changed left ventricular
      ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n = 187) and
      patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0)
      % (n = 179) (p < 0.05). CONCLUSION: Overweight and obesity impair left
      ventricular ejection fraction and global longitudinal strain in both patients
      with type 2 diabetes mellitus and non-diabetic persons. Trial registration
      ClinicalTrials.gov identifier NCT 01049737.

PMID- 30107799
TI  - Barriers to effective communication between family physicians and patients in
      walk-in centre setting in Dubai: a cross-sectional survey.
AB  - BACKGROUND: Effective communication between family physicians and their patients
      is crucial to improving healthcare outcomes and patients' satisfaction. However,
      the barriers to effective communication have been weakly studied in the Gulf
      region with no reported studies in Dubai. This study aims to identify the main
      perceived barriers to effective communication between patients and their family
      physicians in Dubai from both the physicians' and the patients' viewpoints.
      METHODS: The study was conducted at 12 primary healthcare centres in Dubai
      between October 2016 - July 2017. Two self-administered questionnaires were used,
      one measuring the patients' perceived frequency of encounters with barriers to
      communication, while the other was for the family physicians' perceived level of
      risk to communication posed by the barriers. The barriers were assessed in the
      following four domains: personal characteristics and attitudes, organisational
      factors, communication of information, and linguistic and cultural factors.
      RESULTS: There were a total of 1122 patients and 170 family physicians, with 75%
      and 85% response rates, respectively. Having a time limitation was the highest
      ranking barrier, with 23.4% of patients encountering it half of the time-always,
      and 50.6% of physicians perceiving it as moderate-very high risk. This was
      followed by barriers in the communication of information domain, especially not
      checking the patient's understanding and not educating the patient (16.0-16.9%)
      from the patients' perception and presentation with multiple problems and not
      following with a treatment plan (51.2% and 35.9%, respectively), from the
      physicians' perception. Preoccupation with medical records ranked in the second
      pentile for the physicians, and in the lowest pentile for the patients. Barriers
      related to the failure of rapport building and linguistic/cultural factors ranked
      in the fourth and fifth pentiles for both patients and physicians. CONCLUSION:
      Time pressure is the major perceived barrier to communication between patients
      and family physicians. In addition, a greater focus needs to be placed on
      training the physicians to convey their messages to the patients clearly,
      checking their understanding and managing poor historians.

PMID- 30107801
TI  - "You understand that whole big situation they're in": interpretative
      phenomenological analysis of peer-assisted learning.
AB  - BACKGROUND: Peer-assisted learning (PAL) increasingly features within medical
      school curricula. While there is evidence of its effectiveness, less is known
      about how it promotes learning. Cognitive and social congruence between peer
      tutor and student have been described as important concepts underpinning teaching
      and learning in PAL. We employed interpretative phenomenological analysis for an
      in-depth exploration of how medical students experience PAL sessions. METHODS: We
      conducted the study at The University of Manchester within a near-peer scheme
      aimed at developing clinical skills within clinical clerkship students. We
      conducted individual interviews with three peer tutors and five students. We
      undertook interpretive phenomenological analysis of interview transcripts. We
      subsequently synthesised an account of the study participants' lived experiences
      of PAL sessions from individual personal accounts to explore how medical students
      experience peer-assisted learning. This analysis was then used to complement and
      critique a priori educational theory regarding the mechanisms underlying PAL.
      RESULTS: Students experienced PAL sessions as a safe and egalitarian environment,
      which shaped the type and style of learning that took place. This was facilitated
      by close relationships with peer-tutors, with whom they shared a strong sense of
      camaraderie and shared purpose. Peer-tutors felt able to understand their
      students' wider sociocultural context, which was the most important factor
      underpinning both the PAL environment and tutor-student relationship.
      Participants contrasted this relative safety, camaraderie and shared purpose of
      PAL with teaching led by more senior tutors in clinical settings. CONCLUSIONS:
      This study provides a rich description of the important factors that characterise
      medical students' experiences of PAL sessions. Participants felt a strong sense
      of support in PAL sessions that took into account their wider sociocultural
      context. Multiple factors interplayed to create a learning environment and tutor
      student relationship that existed in contrast to teaching led by more senior,
      clinical tutors. The insight generated via IPA complemented existing theory and
      raised new lines of enquiry to better understand how the peer relationship
      fosters learning in PAL at medical school. We make recommendations to use
      insights from PAL for faculty and curriculum development.

PMID- 30107800
TI  - How and why weight stigma drives the obesity 'epidemic' and harms health.
AB  - BACKGROUND: In an era when obesity prevalence is high throughout much of the
      world, there is a correspondingly pervasive and strong culture of weight stigma.
      For example, representative studies show that some forms of weight discrimination
      are more prevalent even than discrimination based on race or ethnicity.
      DISCUSSION: In this Opinion article, we review compelling evidence that weight
      stigma is harmful to health, over and above objective body mass index. Weight
      stigma is prospectively related to heightened mortality and other chronic
      diseases and conditions. Most ironically, it actually begets heightened risk of
      obesity through multiple obesogenic pathways. Weight stigma is particularly
      prevalent and detrimental in healthcare settings, with documented high levels of
      'anti-fat' bias in healthcare providers, patients with obesity receiving poorer
      care and having worse outcomes, and medical students with obesity reporting high
      levels of alcohol and substance use to cope with internalized weight stigma. In
      terms of solutions, the most effective and ethical approaches should be aimed at
      changing the behaviors and attitudes of those who stigmatize, rather than towards
      the targets of weight stigma. Medical training must address weight bias, training
      healthcare professionals about how it is perpetuated and on its potentially
      harmful effects on their patients. CONCLUSION: Weight stigma is likely to drive
      weight gain and poor health and thus should be eradicated. This effort can begin
      by training compassionate and knowledgeable healthcare providers who will deliver
      better care and ultimately lessen the negative effects of weight stigma.

PMID- 30107804
TI  - Prognostic and clinicopathological value of Beclin-1 expression in hepatocellular
      carcinoma: a meta-analysis.
AB  - BACKGROUND: The abnormal expression of Beclin-1 has recently been investigated in
      a variety of tumors. However, previous studies have obtained contradicting
      results regarding the clinical and prognostic value of Beclin-1 in hepatocellular
      carcinoma (HCC). We performed a meta-analysis to clarify the prognostic value of
      Beclin-1 and its correlations with clinical pathological parameters in HCC.
      METHODS: Relevant studies were systematically retrieved from PubMed, EMBASE,
      China National Knowledge Infrastructure (CNKI), Wan Fang and Chinese VIP
      databases. We used the Newcastle-Ottawa scale (NOS) to estimate the quality of
      the involved studies. RESULTS: Ten eligible studies with 1086 HCC patients were
      included in this study. Our results showed that decreased Beclin-1 expression in
      HCC related to histological grade [poor-undifferentiated vs. well-moderate: odds
      ratio (OR) = 2.34, 95% confidence interval (CI) = 1.65-3.32, P < 0.00001]. The
      pooled hazard ratio (HR) (HR = 1.43, 95% CI = 1.17-1.75, P = 0.0004) indicated
      that decreased Beclin-1 expression correlated with poor overall survival (OS).
      CONCLUSIONS: This meta-analysis indicated that decreased Beclin-1 expression
      might relate to poor differentiation and unfavorable outcome in HCC.

PMID- 30107805
TI  - Adding resolution and dimensionality to comparative genomics: moving from
      reference genomes to clade genomics.
AB  - The main goal and promise of comparative genomics has been to create a
      comprehensive catalog of genomic information and function across the phenomenal
      diversity of living systems. A recent study has demonstrated the evolutionary
      insights possible by generating high-quality whole-genome assemblies from
      multiple species of a clade.

PMID- 30107802
TI  - Development and validation of the cancer self-perceived discrimination scale for
      Chinese cancer patients.
AB  - BACKGROUND: To develop a Cancer Self-Perceived Discrimination Scale (CSPDS) for
      Chinese cancer patients and to assess its reliability and validity. METHOD: A
      total of 178 patients were recruited and the classical test theory was used to
      develop the CSPDS. Item analysis was adapted to improve the preliminary version
      of the CSPDS, then the reliability, the validity and the acceptability of the
      final version of CSPDS were assessed. RESULTS: This CSPDS contained 14 items
      classified into 3 subscales: social withdrawal with 7 items, stigma with 4 and
      self-deprecation with 3. Good validity (chi2/df = 1.216, GFI = 0.935, AGFI =
      0.903, I-CVIs> 0.80) and good reliability (Cronbach's alpha = 0.829, Spearman
      Brown coefficient = 0.827, test-retest reliability coefficient = 0.944) were
      found. The completion time was 6.06 +/- 1.80 min. Participants who were female
      and reported poor self-rated health tended to have higher CSPDS scores (P < 
      0.05). CONCLUSIONS: The results indicated that this CSPDS could be used to assess
      the level of self-perceived discrimination and to preliminarily screen perceived
      discrimination among Chinese cancer patients, especially in Southwest China. It
      may provide a basis for scientific assessment of targeted patient education,
      psychological counseling, social interventions, and psychotherapy in the future.

PMID- 30107803
TI  - Molecular characterization of the apoptosis-related SH3RF1 and SH3RF2 genes and
      their association with exercise performance in Arabian horses.
AB  - BACKGROUND: Apoptosis plays an important role in the regulation of healthy tissue
      growth and development as well as in controlling the maintenance of homeostasis
      in exercising muscles. During an intensive physical effort, the regulation of
      cell death by apoptosis results in the replacement of unaccustomed muscle cells
      by new cells that are better suited to exercise. The aim of this study was to
      determine the expression of two genes (SH3FR1 and SH3RF2) that control apoptosis
      in muscle tissues during training periods characterized by different intensities.
      The gene expression levels were estimated using real-time PCR method in skeletal
      muscle biopsies collected from 15 Arabian horses (untrained, after an intense
      gallop phase, and at the end of the racing season). An association study was
      performed on 250 Arabian horses to assess the effect of the SH3RF2:c.796 T > C
      (p.Ser266Pro) variant on race performance traits in flat gallop-racing. RESULTS:
      A gene expression analysis confirmed a significant decrease (p < 0.01) in the
      anti-apoptotic SH3RF2 (POSHER) gene during training periods that differed in
      intensity. The highest SH3RF2 expression level was detected in the muscles of
      untrained horses, whereas the lowest expression was identified at the end of the
      racing season in horses that were fully adapted to the exercise. A non
      significant decrease in SH3RF1 gene expression following the training periods was
      observed. Moreover, a serine substitution by proline at amino acid position 266
      (CC genotype) was negatively associated with the probability of winning races,
      the number of races in which a horse occurred and the financial value of the
      prizes. Horses with the TT genotype achieved the highest financial benefits, both
      for total winnings and for winnings per race in which the horses participated.
      CONCLUSIONS: The present study showed the supposed regulation mechanism of
      exercise-induced apoptosis in horses at the molecular level. The identified
      SH3RF2: c.796 T > C missense variant was associated with selected racing
      performance traits, which is important information during the evaluation of
      horses' exercise predisposition. The association results and frequencies of the
      CT and TT genotypes suggest the possibility of using SH3RF2 variant in selection
      to improve the racing performance of Arabian horses.

PMID- 30107807
TI  - The mode of progressive disease affects the prognosis of patients with metastatic
      breast cancer.
AB  - BACKGROUND: According to the Response Evaluation Criteria in Solid Tumors
      (RECIST), progressive disease (PD) is diagnosed under two conditions: an increase
      in size of pre-existing lesions (IS) and the appearance of new lesions (NL). We
      retrospectively investigated the difference in the prognosis between IS and NL.
      METHODS: Patients receiving drug therapies for metastatic breast cancer between
      2004 and 2015 at our institution were reviewed. The survival time after NL and IS
      was compared and the frequency of NL with each drug calculated. RESULTS: For the
      107 eligible patients, the survival time after NL at second-line chemotherapy was
      significantly worse than after IS (median survival time 4.3 months vs. 20.3
      months, p = 0.0048). Maintenance therapy with bevacizumab or trastuzumab had a
      high frequency of NL (88.9%), and third-line eribulin had a low frequency of NL
      (16.7%). A multivariate analysis showed that NL at second-line chemotherapy was
      not an independent risk factor (hazard ratio 1.02, 95%; confidence interval 0.54
      1.93, p = 0.95) for the total survival time. CONCLUSIONS: Patients with IS had a
      better survival after PD than those with NL. We may be able to avoid changing
      drug therapy for patients without NL and allow them to continue drug therapy for
      longer.

PMID- 30107806
TI  - Corylin inhibits LPS-induced inflammatory response and attenuates the activation
      of NLRP3 inflammasome in microglia.
AB  - BACKGROUND: Inflammation has been found to be associated with many
      neurodegenerative diseases, including Parkinson's and dementia. Attenuation of
      microglia-induced inflammation is a strategy that impedes the progression of
      neurodegenerative diseases. METHODS: We used lipopolysaccharide (LPS) to simulate
      murine microglia cells (BV2 cells) as an experimental model to mimic the
      inflammatory environment in the brain. In addition, we examined the anti
      inflammatory ability of corylin, a main compound isolated from Psoralea
      corylifolia L. that is commonly used in Chinese herbal medicine. The production
      of nitric oxide (NO) by LPS-activated BV2 cells was measured using Griess
      reaction. The secretion of proinflammatory cytokines including tumor necrosis
      factor (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) by LPS
      activated BV2 cells was analyzed using enzyme-linked immunosorbent assay (ELISA).
      The expression of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2),
      nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3
      (NLRP3), apoptosis-associated speck-like protein containing a caspase-activation
      and recruitment domain (ASC), caspase-1, IL-1beta and mitogen-activated protein
      kinases (MAPKs) in LPS-activated BV2 cells was examined by Western blot. RESULTS:
      Our experimental results demonstrated that corylin suppressed the production of
      NO and proinflammatory cytokines by LPS-activated BV2 cells. In addition, corylin
      inhibited the expression of iNOS and COX-2, attenuated the phosphorylation of
      ERK, JNK and p38, decreased the expression of NLRP3 and ASC, and repressed the
      activation of caspase-1 and IL-1beta by LPS-activated BV2 cells. CONCLUSION: Our
      results indicate the anti-inflammatory effects of corylin acted through
      attenuating LPS-induced inflammation and inhibiting the activation of NLRP3
      inflammasome in LPS-activated BV2 cells. These results suggest that corylin might
      have potential in treating brain inflammation and attenuating the progression of
      neurodegeneration diseases.

PMID- 30107808
TI  - From client to co-worker: a case study of the transition to peer work within a
      multi-disciplinary hepatitis c treatment team in Toronto, Canada.
AB  - BACKGROUND: Despite the integration of peer workers into harm reduction services,
      there is little documentation regarding the experience of this integration or of
      models in which peers are fully integrated as members of health care teams. The
      purpose of this study was to gain an in-depth understanding of the transition
      from client to support worker from the perspective of two individuals who
      received treatment for hepatitis C at a multi-disciplinary, community-based
      program, grounded in a harm reduction approach to substance use. METHODS: A
      participatory case study design was selected. Interviews were conducted with two
      current peer workers who were also involved in the study design, analysis and
      writing. Data was coded and analyzed using an inductive approach to identify
      emergent themes. RESULTS: Five primary themes emerged during our analysis of the
      facilitators and challenges of the transition from client to support worker: (1)
      the role of prior experience, (2) changes in substance use practices, (3) shifts
      in relationships with community members and friends, (4) supportive
      organizational and structural factors, and (5) role transition as a journey. In
      some cases, themes overlapped and contained elements that were both facilitating
      and challenging. CONCLUSIONS: The transition from client to co-worker is a
      gradual process and one that is supported by, and in turn helps to support, a
      number of other personal transitions. The cases examined here suggest that a
      model of peer employment with broad qualification criteria, sufficient transition
      timelines, flexible job responsibilities, a solid investment in the inclusion of
      people with lived experience, and a harm reduction framework will support
      successful integration of current and/or former clients into health care teams.

PMID- 30107810
TI  - Investigating enhancer evolution with massively parallel reporter assays.
AB  - A recent study in Genome Biology has characterized the evolution of candidate
      hominoid-specific liver enhancers by using massively parallel reporter assays
      (MPRAs).

PMID- 30107809
TI  - The Heidelberg Milestones Communication Approach (MCA) for patients with
      prognosis <12 months: protocol for a mixed-methods study including a randomized
      controlled trial.
AB  - BACKGROUND: The care needs of patients with a limited prognosis (<12 months
      median) are complex and dynamic. Patients and caregivers must cope with many
      challenges, including physical symptoms and disabilities, uncertainty. and
      compromised self-efficacy. Healthcare is often characterized by disruptions in
      the transition between healthcare providers. The Milestones Communication
      Approach (MCA) is a structured, proactive, interprofessional concept that
      involves physicians and nurses and is aimed at providing coherent care across the
      disease trajectory. This study aims to evaluate these aspects of MCA: (1) the
      training of healthcare professionals, (2) implementation context and outcomes,
      (3) patient outcomes, and (4) effects on interprofessional collaboration.
      METHODS/DESIGN: A multiphase mixed-methods design will be used for the study. A
      total of 100 patients and 120 healthcare professionals in a specialized oncology
      hospital will be involved. The training outcomes will be documented using a
      questionnaire. Implementation context and outcomes will be explored through semi
      structured interviews and written questionnaires with healthcare professionals
      and with the training participants and through a content analysis of patient
      files. Patient outcomes will be assessed in a pragmatic non-blinded randomized
      controlled trial and in qualitative interviews with patients and caregivers.
      Trial outcomes are supportive care needs (SCNS-SF34-G), quality of life (SeiQol
      and Fact-L), depression and anxiety symptoms (PHQ-4), and distress (Distress
      Thermometer). Qualitative semi-structured interviews on patients' views will
      focus on shared decision-making, communication needs, feeling empathy, and
      further utilization of healthcare services. Interprofessional collaboration will
      be explored using the UWE-IP-D before the implementation of MCA (t0) and after 3
      (t1), 9 (t2), and 12 (t3) months. DISCUSSION: Using guideline-concordant early
      palliative care, MCA aims to foster patient-centered communication with shared
      decision-making and facilitation of advance care planning including end-of-life
      decisions, thus increasing patient quality of life and decreasing aggressive
      medical care at the end of life. It is assumed that the communication skills
      training and interprofessional coaching will improve the communication behavior
      of healthcare providers and influence team communications and team processes.
      TRIAL REGISTRATION: German Clinical Trials Register, DRKS00013649 and
      DRKS00013469. Registered on 22 December 2017.

PMID- 30107811
TI  - The effects of bone marrow mononuclear cell transplantation on the quality of
      life of children with cerebral palsy.
AB  - BACKGROUND: Quality of life (QOL) is an important factor in evaluating the
      effectiveness of treatment in children with cerebral palsy (CP). The aim of this
      study was to evaluate the effects of autologous bone marrow mononuclear cells (BM
      MNCs) on the QOL of children with CP. METHODS: From December 2015 to December
      2016, 30 children with CP aged from 2 to 15 years received two intrathecal
      infusions of BM MNCs, one at baseline and the other 3 months later, at Vinmec
      International Hospital. The motor function and muscle tone of the patients were
      evaluated using the Gross Motor Function Measure (GMFM)-88 and Modified Ashworth
      Score, respectively. Their QOL was assessed at baseline and 6 months after the
      first BM MNC transplant using the Vietnamese version of the Cerebral Palsy
      Quality of Life Questionnaire for children (CP QOL-Child)-the parental proxy
      report, which comprises seven domains. Nineteen mothers (mean age: 32.9+/-4.9
      years) and 11 fathers (mean age: 36.1+/-6.8 years) were invited to complete the
      CP QOL-Child assessment before and after the transplantations, Paired t-tests and
      multivariate regression analyses were used to evaluate the changes in QOL and
      GMFM scores and to identify the key factors correlated with the QOL score.
      RESULTS: Significant changes were observed in the children's gross motor function
      and muscle spasticity, as evidenced by the GMFM-88 total score, scores for each
      of its domains, the GMFM-66 percentile and the muscle tone (P < 0.001). Six
      months after the transplantations, the QOL scores of children with CP were
      markedly increased (P < 0.001) for all the domains, except for the domain of
      access to services. In the multivariate regression analysis, significant
      associations were found between higher age of children and higher QOL except for
      feeling about functioning and pain and impact of disability domains. Gross Motor
      Function Classification System (GMFCS) level was negatively correlated with the
      score of pain and impact of disability domain, while the GMFM-88 scores were
      positively correlated with the QOL in terms of feelings about functioning and
      family health domain (P < 0.05). CONCLUSION: The QOL of the children with CP was
      noticeably improved 6 months after BM MNC transplantation and was accompanied by
      improvements in gross motor function and muscle tone. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT02574923 . Registered on October 14, 2015.

PMID- 30107812
TI  - Heterogeneous perception of the ethical legitimacy of unbalanced randomization by
      institutional review board members: a clinical vignette-based survey.
AB  - BACKGROUND: Institutional review boards must guarantee the ethical acceptability
      of a randomized controlled trial before it is conducted. However, some may regard
      an unbalanced randomization ratio as reflecting an absence of uncertainty between
      the groups being compared. The objective was to assess institutional review board
      members' perceptions of whether unbalanced randomization in randomized controlled
      trials is justified and ethically acceptable. METHODS: Institutional review board
      members worldwide completed a survey involving clinical vignettes modeling
      situations classically advocated to explain the use of unbalanced randomization.
      Institutional review board members were asked whether unbalanced randomization
      was justified and ethically sound. Answers were collected by using visual analog
      scales. Data were analyzed by principal component analysis, and a hierarchical
      ascending classification was created. Verbatim answers were assessed by
      qualitative content analysis. RESULTS: We analyzed responses from 148
      institutional review board members. Three classes of respondents were identified:
      class 1 (n = 58; 39.2%), mostly skeptics who disagreed with unbalanced
      randomization, whatever the justification; class 2 (n = 46; 31.1%), believers who
      considered that unbalanced randomization was acceptable whatever the
      justification, except cost; and class 3 (n = 44; 29.7%), circumstantial believers
      for whom unbalanced randomization may be justified for methodological and safety
      issues but not cost or ethical issues. When institutional review board members
      were asked whether unbalanced randomization respected the equipoise principle,
      the mean quotation was low (4.5 +/- 3.3 out of 10), especially for class 1
      members. CONCLUSIONS: Institutional review board members perceive unbalanced
      randomization heterogeneously in terms of its justification and its ethical
      validity.

PMID- 30107813
TI  - Anti-inflammatory activities of Aedes aegypti cecropins and their protection
      against murine endotoxin shock.
AB  - BACKGROUND: Mosquitoes are armed with physiologically active compounds to
      suppress the host immunity including host inflammatory reaction. However, the
      specific anti-inflammatory components in mosquitoes remain unknown. RESULTS: By
      searching for the immunomodulatory molecules from the mosquito Aedes aegypti
      (Diptera: Culicidae) at NCBI for anti-inflammatory function, five cecropins (for
      short in this study: AeaeCec1, 2, 3, 4 and 5) were selected. AeaeCec1-5
      efficiently inhibited the expression of inducible nitric oxide synthase (iNOS),
      nitrite, tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta)
      and interleukin-6 (IL-6) in lipopolysaccharide (LPS)-stimulated mouse peritoneal
      macrophages and human peripheral blood mononuclear cells (PBMCs) with low
      toxicity to mammalian cells. Among the five analogues, AeaeCec5 had the strongest
      anti-inflammatory activity, and generated an additive effect with other AeaeCec
      peptides. In a mouse model of endotoxin shock, AeaeCec1-5 effectively reduced TNF
      alpha, IL-1beta and IL-6 expression in lungs, serum and peritoneal lavage and
      correspondingly reduced lung damage and edema, with AeaeCec5 showing the best
      protection. In mice infected with Escherichia coli or Pseudomonas aeruginosa,
      administration of AeaeCec5 reduced the production of TNF-alpha, IL-1beta and IL-6
      and correspondingly reduced lung tissue damage. These effects of Ae. aegypti
      AeaeCec1-5 were attributed to an efficient inhibition of the activation of
      mitogen-activated protein kinases (MAPKs) and transcriptional nuclear factor
      kappaB (NF-kappaB) signaling pathways, as well as partial neutralization of LPS.
      CONCLUSIONS: The current work characterized the specific anti-inflammatory agents
      in Ae. aegypti and provided AeaeCec5 as a potent anti-endotoxin peptide that
      could serve as the basis for the development of anti-inflammatory therapy.

PMID- 30107814
TI  - The EKSPECT study: the influence of Expectation modification in Knee arthroplasty
      on Satisfaction of PatiEnts: study protocol for a randomized Controlled Trial.
AB  - BACKGROUND: One out of five patients is unsatisfied to some extent after total
      knee arthroplasty (TKA). Unmet expectations are the main driver of post-operative
      dissatisfaction. Improved pre-operative education on realistic expectations for
      long-term outcome after TKA potentially leads to higher post-operative
      satisfaction. The effect of expectation modification on post-operative
      satisfaction in TKA patients has not yet been studied. The primary objective of
      the presented study is to examine whether an educational module on long-term
      recovery after TKA will improve patient satisfaction compared to usual pre
      operative education. METHODS: The EKSPECT study is a randomized controlled trial.
      Patients with symptomatic and radiographic knee osteoarthritis who are indicated
      for a primary TKA will be randomized to the usual pre-operative education
      (control group) or usual education plus an additional module on realistic
      expectations for long-term recovery (intervention group). Patients will be naive
      to study objective and difference between study groups. Outcome expectations will
      be measured blinded for group allocation using the HSS Knee Replacement
      Expectations Survey at baseline (before the intervention), pre-operatively (after
      the intervention) and fulfillment of expectations at 12-month follow-up. Baseline
      physical function, quality of life and psychological factors are measured using
      self-reported questionnaires. The primary outcome measure is satisfaction with
      treatment result at the 12-month follow-up. DISCUSSION: The EKSPECT study should
      provide evidence on the effectiveness of an education module on long-term
      recovery after TKA to improve treatment satisfaction. If beneficial, the
      education module is a simple intervention with a low burden for patients, which
      can easily be implemented in clinical practice. TRIAL REGISTRATION: Dutch Trial
      Registry registration number: NTR5779 . Registered on 17 March 2016.

PMID- 30107815
TI  - Bionomics and vectorial role of anophelines in wetlands along the volcanic chain
      of Cameroon.
AB  - BACKGROUND: The epidemiological profiles of vector-borne diseases, such as
      malaria, are strongly associated with landscape components. The reduction of
      malaria burden in endemic and epidemic regions mainly depends on knowledge of the
      malaria-transmitting mosquito species, populations and behavioural
      characteristics, as well as malaria exposure risks. This work aimed at carrying
      out a holistic study in order to characterise Anopheles species in relation to
      human malaria in seven wetlands along the lower section of the volcanic chain of
      Cameroon. RESULTS: Eight malaria vectors: Anopheles arabiensis, An. coluzzii, An.
      funestus (s.s.), An. gambiae, An. hancocki, An. melas, An. nili and An. ziemanni,
      were found biting humans. Anopheles gambiae was widespread; however, it played a
      secondary role in the Ndop plain where An. ziemmani was the primary vector
      species (79.2%). Anophelines were more exophagic (73.6%) than endophagic (26.4%),
      showing a marked nocturnal activity (22:00-4:00 h) for An. coluzzii and An.
      gambiae while An. funestus (s.s.) was mostly caught between 1:00 and 6:00 h and
      An. ziemanni having an early evening biting behaviour (18:00-00:00 h). Female
      Anopheles were mostly observed to have relative high parity rates (>= 70%), with
      the exception of the Meanja site where species parity varies from 46 to 55%.
      Overall, the transmission level was low with entomological inoculation rates
      estimated to 0.7 infected bites per person per month (ib/p/mth) in Tiko and Ndop,
      1.4 ib/p/mth in Mamfe and 2.24 ib/p/mth in Santchou. CONCLUSIONS: The present
      study represents detailed Anopheles vector characterisation from an understudied
      area along the volcanic chain of Cameroon with endemic malaria transmission. The
      significant differences in bionomics and Anopheles species distribution within
      the studied wetlands, highlights the importance of providing baseline data and an
      opportunity to assess the outcome of ongoing malaria control interventions in the
      country.

PMID- 30107816
TI  - Adherence to anti-vectorial prevention measures among travellers with chikungunya
      and malaria returning to Australia: comparative epidemiology.
AB  - OBJECTIVE: Compare the adoption and adherence to health protection behaviours
      prior to and during travel among international Australian travellers who return
      to Australia with notified chikungunya or malaria infection. This information
      could inform targeted health promotion and intervention strategies to limit the
      establishment of these diseases within Australia. RESULTS: Seeking travel advice
      prior to departure was moderate (46%, N = 21/46) yet compliance with a range of
      recommended anti-vectorial prevention measures was low among both chikungunya and
      malaria infected groups (16%, N = 7/45). Reasons for not seeking advice between
      groups was similar and included 'previous overseas travel with no problems' (45%,
      N = 9/20) and 'no perceived risk of disease' (20%, N = 4/20). Most chikungunya
      cases (65%, N = 13/20) travelled to Indonesia and a further 25% (N = 5/20)
      visited India, however most malaria cases (62%, N = 16/26) travelled to
      continental Africa with only 12% (N = 3/26) travelling to India. The majority
      (50%, N = 10/20) of chikungunya cases reported 'holiday' as their primary purpose
      of travel, compared to malaria cases who most frequently reported travel to visit
      friends and family (VFR; 42%, N = 11/26). These results provide import data that
      may be used to support distinct public health promotion and intervention
      strategies of two important vector-borne infectious diseases of concern for
      Australia.

PMID- 30107818
TI  - Psychological features of abstinent heroin users before and after rehabilitation
      in Saint Petersburg, Russia.
AB  - OBJECTIVE: The objective of the study was to describe psychological features of
      abstinent heroin users undergoing rehabilitation in Saint Petersburg, Russia.
      Study subjects (n = 197) were recruited prospectively at the time of their
      admission to rehabilitation between March 2010 and May 2011 at 7 inpatient opiate
      addiction rehabilitation centers in Saint-Petersburg and neighboring regions,
      Russia. The centers provided varying rehabilitation programs; 6 of them were
      religious centers. Socio-demographic information and self-reported HIV status
      were collected. Personality profiles and severity of drug-associated problems
      were estimated before and after rehabilitation using the Minnesota Multiphasic
      Personality Inventory 2 (MMPI-2), and the Addiction Severity Index (ASI).
      RESULTS: Thirty-three (17%) subjects dropped out before completing rehabilitation
      (non-completers). All subjects (completers and non-completers) had
      psychopathological personality profiles according to MMPI-2. These profiles were
      refractory to clinically significant improvement after rehabilitation, although
      some statistically significant changes toward improvement were observed. ASI
      scores showed statistically and clinically significant improvements after
      rehabilitation on all scales. Participants in longer-term versus shorter-term
      rehabilitation programs showed similar changes in their pre- and post
      rehabilitation MMPI-2 and ASI scores. Our results suggest that unmet psychiatric
      needs should be addressed to potentially improve treatment completion in this
      population.

PMID- 30107817
TI  - Mosquito microbiota cluster by host sampling location.
AB  - BACKGROUND: Microbial communities that inhabit the mosquito body play an import
      role in host biology and may have potential for mosquito control. However, the
      forces that shape these microbial communities are poorly understood. METHODS: To
      gain a better understanding of how host location influences the composition and
      diversity of mosquito microbiota, we performed a survey of microbial communities
      in mosquito samples collected from six USA states using HiSeq sequencing of the
      16S rRNA gene. RESULTS: A total of 284 bacterial operational taxonomic units
      (OTUs) belonging to 14 phyla were detected in nine mosquito species, with
      Proteobacteria, Firmicutes and Actinobacteria accounting for 95% of total
      sequences. OTU richness varied markedly within and between mosquito species. The
      microbial composition and diversity was heavily influenced by the site of
      mosquito collection, suggesting that host location plays an important role in
      shaping the mosquito microbiota. CONCLUSIONS: Variation in microbial composition
      and diversity between mosquitoes from different locations may have important
      implications on vector competence and transmission dynamics of mosquito-borne
      pathogens. Future studies should investigate the environmental factors
      responsible for these variations and the role of key bacteria characterized in
      this study on mosquito biology and their potential application in symbiotic
      control of mosquito-borne diseases.

PMID- 30107819
TI  - The "Wholesome Contact" non-pharmacological, volunteer-delivered
      multidisciplinary programme to prevent hospital delirium in elderly patients:
      study protocol for a randomised controlled trial.
AB  - BACKGROUND: In hospital settings, delirium affects as many as 50% of older
      patients, aggravating their symptoms and worsening their condition, and therefore
      increasing the risk of in-hospital complications and death. The aim of this study
      is to assess the efficacy of structured, non-pharmacological care, delivered to
      older hospitalised patients by trained volunteers (students of medical fields),
      on the reduction of incidence of adverse health-related outcomes. METHODS/DESIGN:
      This trial will be a randomised, investigator-blind, controlled trial conducted
      in an internal medicine and geriatric ward in Poland. We aim to include 416
      patients who are 70 years of age and have been hospitalised for medical reasons.
      Eligible patients will be randomised 1:1 to receive structured, non
      pharmacological care delivered by students of medicine, psychology and nursing,
      together with standard medical treatment or standard medical care alone. The
      protocol of interventions has been designed to cover nine main risk factors for
      delirium, with the scope of multidisciplinary interventions being individualised
      and tailored. The protocol will be aimed at immobilisation, vision and hearing
      impairment, cognitive impairment and disorientation, stress and anxiety, sleep
      wake cycle disturbances, dehydration and malnutrition, and pain. A structured
      evaluation of patients' cognition, mood, anxiety and functional performance is
      planned to be carried out twice, on the day of group allocation and at discharge;
      structured screening assessment for delirium will be conducted daily using the
      Confusion Assessment Method. The primary outcome will be the incidence of
      delirium in hospital; secondary outcomes will be in-hospital changes in
      cognition, mood and anxiety, and functional status, occurrence of falls and
      death. DISCUSSION: Delirium prevention programmes are being introduced worldwide.
      A particular novelty of our project, however, is that invitations for voluntary
      work with older patients at risk for delirium will be addressed to medical
      students. With the use of the service learning method, the students will shape
      their attitudes, increase their knowledge and understanding of hospital care, and
      master competencies to work within interdisciplinary teams, which establishes the
      originality and practicality of the project. TRIAL REGISTRATION: Polish Science
      Database, 317484 . Registered on 23 October 2016.

PMID- 30107821
TI  - Correction to: miR-155 is dispensable in monosodium urate-induced gouty
      inflammation in mice.
AB  - Unfortunately, after publication of this article [1], it was noticed that 2
      authors were erroneously mentioned as co-first authors.

PMID- 30107820
TI  - High genetic diversity in hard ticks from a China-Myanmar border county.
AB  - BACKGROUND: Many tick species have great morphological similarity and are thus
      grouped into species complexes. Molecular methods are therefore useful in the
      classification and identification of ticks. However, little is known about the
      genetic diversity of hard ticks in China, especially at the subspecies level.
      Tengchong is one of the epidemic foci of tick-borne diseases in China, but the
      tick species inhabiting the local area are still unknown. METHODS: Eighteen
      villages in Tengchong County, China, were selected for sampling carried out from
      September to October 2014. Infesting hard ticks were removed from the body
      surface of domestic animals and questing ticks were collected from grazing
      fields. After morphological identification, molecular characteristics of each
      tick species were analyzed based on both 16S rRNA and cytochrome c oxidase
      subunit 1 (cox1) gene fragments. RESULTS: Six tick species were identified based
      on morphology: Rhipicephalus microplus, R. haemaphysaloides, Ixodes ovatus,
      Haemaphysalis longicornis, H. shimoga and H. kitaokai. Phylogenetic analysis
      using the cox1 gene revealed that R. microplus ticks from the present study
      belong to clade C. For tick samples of both R. haemaphysaloides and I. ovatus,
      three phylogenetic groups were recognized, and the intergroup genetic distances
      exceeded the usual tick species boundaries. Haemaphysalis longicornis ticks were
      clustered into two separate clades based on the cox1 gene. For ticks from both H.
      shimoga and H. kitaokai, two phylogenetic groups were recognized based on the
      phylogenetic analysis of the 16S rRNA gene, and the intergroup genetic distances
      also exceeded the known boundaries for closely related tick species. CONCLUSIONS:
      According to molecular analyses, new species or subspecies closely related to R.
      haemaphysaloides, I. ovatus, H. shimoga and H. kitaokai probably exist in the
      China-Myanmar border Tengchong County, or these ticks form species complexes with
      highly divergent mitochondrial lineages. Morphological comparisons are warranted
      to further confirm the taxonomic status of these tick species.

PMID- 30107823
TI  - Gender of children and social provisions as predictors of unplanned pregnancies
      in Pakistan: a cross-sectional survey.
AB  - OBJECTIVE: Previous research indicates that attitudes to pregnancy and motherhood
      are influenced by social values, culture and religion. This study explores the
      relationship between social support and unwanted pregnancy among Pakistani women.
      This cross-sectional study was conducted at four teaching hospitals in Lahore in
      2014. RESULTS: A total of 500 pregnant women who visited the hospitals'
      obstetrics and gynecology departments were asked to respond to a questionnaire
      consisting of respondents' characteristics and the Social Provisions Scale (SPS).
      Logistic regression analyzed the predictors of unplanned pregnancy. Unwanted
      pregnancies were more likely to occur among pregnant women from rural areas, with
      low scores on the SPS 'reassurance of worth' sub-scale, no history of
      contraceptive use, and who already had at least one son than those with no sons.

PMID- 30107822
TI  - Dengue fever manifesting with tetany as the first presentation of primary
      hypoparathyroidism: a case report.
AB  - BACKGROUND: Primary hypoparathyroidism is associated with diverse variety of
      symptomatology of hypocalcemia including seizures and tetany. We report a case of
      previously undiagnosed asymptomatic primary hypoparathyroidism with extensive
      basal ganglia calcifications presenting for the first time with hypocalcemic
      tetany during acute dengue infection. Although hypocalcemia is known to occur in
      dengue infection symptomatic hypocalcemia is very infrequent. CASE PRESENTATION:
      A 32 year old male with short stature who has undergone bilateral cataract
      surgery 2 years ago but who was otherwise healthy, presented with fever and
      generalized body aches of 3 days duration and carpal spasms/tetany occurring on
      the third day of the illness. He was diagnosed to have acute dengue fever along
      with severe hypocalcemia. Subsequent workup confirmed that the patient had
      primary hypoparathyroidism with extensive basal ganglia and cerebellar
      calcifications which was previously undiagnosed. His acute illness and
      hypocalcemia was managed successfully and was commenced on regular calcium
      supplementations to alleviate the hypocalcemic effects of his chronic illness.
      CONCLUSION: Clinical features of hypocalcemia may not commonly manifest up to the
      same degree of severity of hypocalcemia in primary hypoparathyroidism even till
      late adulthood but potential early clues such as short stature and premature
      cataract should be actively investigated. Worsening of already existing
      hypocalcemia during acute dengue fever led to the ultimate diagnosis of primary
      hypoparathyroidism in this patient which was lifesaving.

PMID- 30107824
TI  - Epidemiology of measles in the metropolitan setting, Addis Ababa, Ethiopia, 2005
      2014: a retrospective descriptive surveillance data analysis.
AB  - BACKGROUND: Measles is a highly infectious and serious respiratory viral disease
      which caused by a virus. It is a significant cause of illness and death
      worldwide. This data analysis was conducted to describe the trend and determine
      the reporting rate of measles cases in Addis Ababa to make recommendation for the
      government of the city to strengthening measles control interventions. METHODS:
      We obtained and extracted ten years (2005-2014) Addis Ababa city's measles
      surveillance data from national database. We carried out retrospective
      descriptive data analysis by time, place and person variables. We calculated
      cumulative and specific reporting rates by dividing measles cases (lab confirmed,
      epidemiologically linked and compatible cases) to respective population and
      multiplying by 100,000. We divided average of ten years measles cases to midyear
      population and multiplied by 100,000 to calculate annualized reporting rate. We
      analyzed non-measles febrile rash rate by dividing laboratory negative cases to
      total population and multiplying by 100,000. RESULTS: A total of 4203 suspected
      measles cases were identified. Among them 1154 (27.5%) were laboratory confirmed,
      512 (12.2%) were clinically compatible, 52 (1.2%) were epidemiologically linked
      cases and the rest 2485 (59.1%) were IgM negative for measles which makes total
      measles cases 1718 (40.9%). Median age was 5 years with 2-18 years interquartile
      range. The annualized measles reporting rate was 5.9, which was 40.2 among > 1
      year, 11.5 among 1-4 years, 6.0 among 5-14 years, 4.1 among 15-44 years and 0.01
      among >= 45 years per 100,000 population. Among the total measles cases; 380
      (22%) were received at least one dose of measles containing vaccine (MCV) while
      415 (24%) cases were not vaccinated and the vaccination status of 923 (54%) cases
      were not known. CONCLUSION: Our analysis revealed that the reporting rate was
      higher among young children than older age group. Among all the patients 22% were
      received at least one dose of measles vaccine whereas 13% were not vaccinated
      against measles antigen. Routine immunization should be strengthened to reach all
      children through well monitored vaccine cold chain management.

PMID- 30107826
TI  - Rapid and sensitive detection of Yersinia pestis by lateral-flow assay in
      simulated clinical samples.
AB  - BACKGROUND: Yersinia pestis is a contributing agent to the epidemic disease,
      plague, which killed an estimated 200 million people during historical times. In
      this study, a rapid, cheap, sensitive, and specific technique, the lateral flow
      assay (F1 strips), has been successfully developed to detect this pathogen, by
      using paired monoclonal antibodies (MAbs) against Y. pestis capsule like fraction
      1 (F1) protein. Compared with the polyclonal antibody (PAb) based F1 strips, the
      Mab-based F1 strips have a remarkable increased detection limitation (10 to 100
      folds). Furthermore, besides the limitation and specificity evaluation, the
      application of this F1 strip on simulated clinical samples indicate the LFA can
      be a good candidate to detect plague. METHODS: Recombinant F1 antigen was
      expressed and purified from a series of works. The various anti-F1 monoclonal
      antibodies generated from hybridoma cells were screened with the ELISA technique.
      To evaluate the feasibility of this Y. pestis F1 test strip, the F1 protein/Y.
      pestis was spiked into simulated clinical samples such as human serum, mouse
      bronchoalveolar lavage fluids, and mouse blood to mimic natural infection status.
      Additionally, this technique was applied to detect the Y. pestis in the
      environment-captured rats, to evaluate the practical usefulness of the strips.
      RESULTS: By using this MAb-based-LFA technique, 4 ng/ml of recombinant F1-protein
      and 103 CFU/ml of Y. pestis could be detected in less than 10 mins, which is at
      least 10-folds than that of the PAb format. On the other hand, although various
      Yersinia strains were applied to the strips, only Y. pestis strain showed a
      positive result; all other Yersinia species did not produce a positive signal,
      indicating the high efficiency and specificity of the MAb-based F1-strips.
      CONCLUSION: Based on our findings, we suggest that the MAb-format-LFA will be
      valuable as a diagnostic tool for the detection of Y. pestis. This report shows
      that the F1 strip is sufficient to support not only the detection of plague in
      simulated clinical samples, but also it may be a good candidate to meet the
      epidemiological surveillance during an outbreak of the biological warfare.

PMID- 30107825
TI  - Examining transcriptional changes to DNA replication and repair factors over
      uveal melanoma subtypes.
AB  - BACKGROUND: Uncontrolled replication is a process common to all cancers
      facilitated by the summation of changes accumulated as tumors progress. The aim
      of this study was to examine small groups of genes with known biology in
      replication and repair at the transcriptional and genomic levels, correlating
      alterations with survival in uveal melanoma tumor progression. Selected
      components of Pre-Replication, Pre-Initiation, and Replisome Complexes, DNA
      Damage Response and Mismatch Repair have been observed. METHODS: Two groups have
      been generated for selected genes above and below the average alteration level
      and compared for expression and survival across The Cancer Genome Atlas uveal
      melanoma subtypes. Significant differences in expression between subtypes
      monosomic or disomic for chromosome 3 have been identified by Fisher's exact
      test. Kaplan Meier survival distribution based on disease specific survival has
      been compared by Log-rank test. RESULTS: Genes with significant alteration
      include MCM2, MCM4, MCM5, CDC45, MCM10, CIZ1, PCNA, FEN1, LIG1, POLD1, POLE,
      HUS1, CHECK1, ATRIP, MLH3, and MSH6. Exon 4 skipping in CIZ1 previously
      identified as a cancer variant, and reportedly used as an early serum biomarker
      in lung cancer was found. Mismatch Repair protein MLH3 was found to have splicing
      variations with deletions to both Exon 5 and Exon 7 simultaneously. PCNA, FEN1,
      and LIG1 had increased relative expression levels not due to mutation or to copy
      number variation. CONCLUSION: The current study proposes changes in relative and
      differential expression to replication and repair genes that support the concept
      their products are causally involved in uveal melanoma. Specific avenues for
      early biomarker identification and therapeutic approach are suggested.

PMID- 30107827
TI  - A comparison of the larvivorous habits of exotic Poecilia reticulata and native
      Aplocheilus parvus.
AB  - BACKGROUND: The exotic fish Poecilia reticulata is promoted in the tropics as a
      biological control agent for aquatic pathogenic carriers, such as mosquitoes.
      Such control measures are often adopted blindly, ignoring the potential of native
      species and the adverse effects of introduced species. The present study was
      conducted to assess the diet composition of two species of fish, the native
      Aplocheilus parvus and exotic P. reticulata, and to assess the availability of
      food items in their natural environment in four types of aquatic systems. Diet
      composition was estimated using 24 h gut contents analysis, in a clay quarry pit
      and a perennial reservoir for A. parvus, and in a man-made canal and a second
      order natural stream for P. reticulata. Food items in these environments were
      quantified by analyzing water samples collected every 2 h. RESULTS: The diet of
      A. parvus in the clay quarry pit and reservoir consisted of adult or larval
      stages of Insecta, Maxillopoda and Malacostraca. In both habitats, A. parvus
      selectively fed on insect parts and insect larvae. The diet of P. reticulata
      consisted of filamentous algae, diatoms and detritus. The diet of A. parvus
      showed active selection of insectivore food items against their low availability.
      In contrast, the diet of P. reticulata showed consumption of food items in
      accordance with their availability in the environment. The highest mean number of
      food items in the gut for A. parvus was recorded around mid-day in the clay
      quarry pit, but no peak feeding time was identified in the perennial reservoir.
      For P. reticulata, peak feeding was recorded around mid-day in both the habitats.
      CONCLUSION: Irrespective of the type of environment and rate of occurrence, A.
      parvus preferred insect and insect larvae, whereas P. reticulata consumed the
      most readily available food items. The active selection of insects by A. parvus
      suggests they may have value as a biological control agent.

PMID- 30107828
TI  - Studying the factors related to refractive error regression after PRK surgery.
AB  - BACKGTOUND: Photorefractive keratectomy (PRK) is used for a wide range of
      refractive errors such as low to moderate myopia, hyperopia and astigmatism.
      While many improvements have been made in laser application and accuracy as well
      as the modes of corneal flap removal, and although the results are somewhat
      predictable, regression of refractive errors is still a common complaint among
      the patients undergoing refractive surgery with Excimer Laser. We aimed to
      determine related factors of regression following photorefractive keratectomy
      (PRK) in different types of refractive errors. METHODS: This cross-sectional
      study included patients who had undergone PRK more than 6 months previously and
      investigated refractive error regression and related factors. The participants
      were those who had PRK eye surgery for the first time from 2013 to 2016 using
      Technolas 217z100. A refraction value of spherical equivalent > 0.75 D after
      cycloplegic refraction was defined as refractive error regression. RESULTS: A
      total of 293 eyes on 150 subjects were studied. The preoperative refractive error
      of the eyes were as follows: 5.5% were myopic, 1% were hyperopic, 4.8% had
      astigmatism, 76% had myopic astigmatism and 12.6% had hyperopic astigmatism.
      Regressed and non-regressed eyes were assessed using the generalized estimating
      equations for the probabilistic variables of demographic characteristics,
      topography and eye refraction. The variables of simulated keratometry astigmatism
      (simK) (OR = 2.8; p = 0.04), 5 mm irregularity (OR = 3.56; p = 0.01) and sphere
      value (OR = 1.98; p = 0.01) were significantly related to refractive error
      regression. There was no significant relationship between the regressed and non
      regressed eyes of the same person (p >= 0.05). CONCLUSION: There was a positive
      relationship between the increase of 5 mm irregularity, simK, sphere value before
      surgery and refractive error regression. Age, sex and type of refraction error of
      the patient and the expertise of the PRK surgeon could change the general
      results; therefore, not all cases should be dealt with identically.

PMID- 30107829
TI  - Myalgia caused by chronic myositis associated with plasmacytosis: a case report.
AB  - BACKGROUND: Cutaneous and systemic plasmacytosis are skin disorders characterized
      by cutaneous polyclonal plasma cell infiltration accompanied by polyclonal
      hypergammaglobulinemia. Cutaneous plasmacytosis involvement is limited to the
      skin, mainly on the face and trunk, while systemic plasmacytosis also involves 2
      or more organ systems. However, there have been no reports of inflammatory
      myositis due to plasmacytosis. Here, we report a patient with plasmacytosis who
      developed myalgia and easy fatigability due to inflammatory myositis. CASE
      PRESENTATION: A 54-year-old man with cutaneous plasmacytosis on the face, chest,
      and back complained of a history of atypical facial and lower leg pain and easy
      fatigability since the age of 45 years. Muscle-strength tests revealed bilateral
      trivial gastrocnemius weakness with myalgia. The results of routine blood
      analysis, including creatine kinase and thyroid function, were normal, but levels
      of several inflammation markers and autoantibodies were elevated. Additionally,
      lower leg magnetic resonance imaging and gastrocnemius muscle biopsy revealed
      inflammatory myositis mimicking polymyositis. His plasmacytosis, myalgia, and
      lower leg weakness were ameliorated by prednisolone. CONCLUSION: The patient was
      diagnosed with inflammatory myositis due to plasmacytosis. Given that
      plasmacytosis has previously been reported to disrupt the immune status, myositis
      in this patient might have been associated with abnormal autoimmune inflammation.
      Neurologists and physicians should thus be aware that plasmacytosis might be
      associated with inflammatory myositis accompanied by myalgia.

PMID- 30107831
TI  - Review of guidelines on expression, storage and transport of breast milk for
      infants in hospital, to guide formulation of such recommendations in Sri Lanka.
AB  - BACKGROUND: Sick newborns in neonatal units who are unable to breastfeed are fed
      expressed breast milk. In Sri Lanka, most mothers stay in hospital throughout
      baby's stay to provide this milk freshly. In other countries mothers go home,
      express breast milk at home and bring it to hospital. There are concerns about
      the safety of transported expressed milk if used in a tropical middle-income
      country. The aim of this paper is to compare and contrast advice offered by
      different hospitals and organizations on how to express, store and transport
      breast milk safely. METHODS: We assessed guidelines used by hospital staff of the
      four Level 3 neonatal units in Melbourne, Australia, National Health Service UK,
      guidelines and training manuals of the Human Milk Banking Association of North
      America, the World Health Organization and an information leaflet from Family
      Health Bureau, Sri Lanka. Information on breast milk expression, storage and
      transport provided by the guidelines were tabulated under seven topics: general
      information; container for milk collection; hand expression; using a pump for
      expression; storage; thawing / warming; and transport of expressed breast milk.
      The AGREE II tool was used to assess the guidelines written for hospital staff.
      RESULTS: There was considerable agreement on most recommendations provided by
      these sources, but no single source covered all topics in full. Most recommend
      hand expression as the initial method for expressing of breast milk, followed by
      breast pump use, except the Sri Lankan recommendations which strongly discourages
      the use of breast pumps. Durations of storage under various conditions are
      generally similar in the different recommendations. Most guidelines recommend a
      'cool box' or container with ice or freezer packs for transportation of milk.
      CONCLUSION: A single document containing recommendations on all aspects of
      expressing, storing and transporting breast milk should be available for each
      unit, with the same basic information for mothers and the healthcare staff and
      further technical details for staff if required. The Sri Lankan recommendations
      need to be updated based on current worldwide practices and further studies are
      needed to establish a safe method of transport of expressed breast milk in Sri
      Lanka.

PMID- 30107830
TI  - Sero-prevalence of yellow fever and related Flavi viruses in Ethiopia: a public
      health perspective.
AB  - BACKGROUND: Yellow fever (YF) is a viral hemorrhagic fever, endemic in the
      tropical forests of Africa and Central and South America. The disease is
      transmitted by mosquitoes infected with the yellow fever virus (YFV). Ethiopia
      was affected by the largest YF outbreak since the vaccination era during 1960
      1962. The recent YF outbreak occurred in 2013 in Southern part of the country.
      The current survey of was carried out to determine the YF seroprevalence so as to
      make recommendations from YF prevention and control in Ethiopia. METHODOLOGY: A
      multistage cluster design was utilized. Consequently, the country was divided
      into 5 ecological zones and two sampling towns were picked per zone randomly. A
      total of 1643 serum samples were collected from human participants. The serum
      samples were tested for IgG antibody against YFV using ELISA. Any serum sample
      testing positive by ELISA was confirmed by plaque reduction neutralization test
      (PRNT). In addition, differential testing was performed for other flaviviruses,
      namely dengue, Zika and West Nile viruses. RESULT: Of the total samples tested,
      10 (0.61%) were confirmed to be IgG positive against YFV and confirmed with PRNT.
      Nine (0.5%) samples were antibody positive for dengue virus, 15(0.9%) forWest
      Nile virus and 7 (0.4%) for Zika virus by PRNT. Three out of the five ecological
      zones namely zones 1, 3 and 5 showed low levels (< 2%) of IgG positivity against
      YFV. A total of 41(2.5%) cases were confirmed to be positive for one of
      flaviviruses tested. CONCLUSION: Based on the seroprevalence data, the level of
      YFV activity and the risk of a YF epidemic in Ethiopia are low. However
      additional factors that could impact the likelihood of such an epidemic occurring
      should be considered before making final recommendations for YF prevention and
      control in Ethiopia. Based on the results of the serosurvey and other YF epidemic
      risk factors considered, a preventive mass vaccination campaign is not
      recommended, however the introduction of YF vaccine in routine EPI is proposed
      nationwide, along with strong laboratory based YF surveillance.

PMID- 30107832
TI  - Time trends and future prediction of coal worker's pneumoconiosis in opencast
      coal mine in China based on the APC model.
AB  - BACKGROUND: The opencast coal mine is a specific mine differing from the
      underground mine. There are differences in the way into the ore body, the
      organization of production, transport technology and other aspects. This study
      aimed to describe the prevalence of CWP among ex-dust miners in opencast coal
      mines and estimate the incidence trend of CWP by APC model in the future.
      METHODS: All opencast miners who had been exposed to dust for at least 1 year in
      opencast mines were enrolled in this study. The database included demographic
      details, occupational history records with the date of dust exposure, physical
      examination records and pneumoconiosis diagnosis records. An age-period-cohort
      (APC) model has been carried out in order to explore the effects of the age,
      period and cohort on the prevalence of CWP among ex-dust opencast miners.
      RESULTS: 8191 opencast miners were enrolled in the study, including 259 miners
      with CWP and 7932 miners without CWP. The incidence density of CWP would have an
      increasing trend in opencast mines from 2005 to 2024. The number of possible CWP
      patients predicted in this period was approximately 492. Of them, 275 miners
      could have suffered from CWP in 2005-2014 and 217 miners would suffer from CWP in
      2015-2024 among the ex-dust opencast miners. CONCLUSIONS: The APC model had a
      goodness of fit in predicting the incidence trend of CWP in opencast coal mines.
      By this model, we predicted that 492 opencast miners could be diagnosed as CWP
      from 2005 to 2024. Therefore ex-dust opencast miners cannot be ignored and they
      should have regular physical examinations and detection for CWP.

PMID- 30107834
TI  - Usage of glaucoma-specific patient-reported outcome measures (PROMs) in the
      Singapore context: a qualitative scoping exercise.
AB  - BACKGROUND: Despite the increasing emphasis on the role of glaucoma-specific
      patient-reported outcome measures (PROMs) as relevant outcome measures for the
      impact of glaucoma and its intervention on patients' daily lives, the feasibility
      of implementing PROMs in the routine clinical setting in Singapore remains
      undefined. We aim to evaluate the comprehensibility, acceptability, and relevance
      of four glaucoma-specific PROMs at healthcare professionals' and patients' level
      in a Singapore context. METHODS: Sixteen ophthalmic healthcare professionals and
      24 glaucoma patients, with average age 60 years (SD = 15), were invited from a
      tertiary hospital in Singapore. Semi-structured interviews were conducted to
      explore participants' perceptions on the content and administration of four
      glaucoma-specific PROMs - the Glaucoma Quality of Life-15, Glaucoma Symptom
      Identifier, Independent Mobility Questionnaire and Treatment Satisfaction Survey
      of Intra-ocular Pressure. Semi-structured interviews were hand transcribed, and
      analysed thematically. Each participant filled out a feasibility survey at the
      end of interview. RESULTS: 79% of glaucoma patients and 94% of glaucoma
      healthcare professionals felt selected PROMs relevant to patients. 63% of
      glaucoma patients and 50% of healthcare professionals felt that selected PROMs
      were sufficiently comprehensive for clinical use. 46% of glaucoma patients and
      56% of healthcare professionals felt selected PROMs were user-friendly.
      CONCLUSIONS: Using PROMs in the Singapore clinical setting receives promising
      support from both healthcare professionals and patients. The identified potential
      barriers tailored to Singapore clinical setting will help successful
      implementation of PROMs into routine clinical care.

PMID- 30107835
TI  - A case report of Werner's syndrome with bilateral juvenile cataracts.
AB  - BACKGROUND: To report a case of Werner's syndrome with bilateral juvenile
      cataracts. CASE PRESENTATION: Review of the clinical, laboratory, photographic,
      genetic testing of the patient. A 26-year-old Chinese man presented with impaired
      vision in both eyes for more than a year. Anterior segment examination of both
      eyes revealed cataract. According to the ocular symptoms and systemic signs,
      including low body weight, a short stature, a bird-like face, atrophic and
      scleroderma-like skin, in addition to the juvenile cataracts, the clinical
      diagnosis of Werner's syndrome was made. Next-generation sequencing identified a
      homozygous WRN mutation in this patient. CONCLUSIONS: The ocular and systemic
      findings in this patient in combination with the homozygous WRN mutation
      indicated the definitive Werner's syndrome diagnosis.

PMID- 30107836
TI  - Helcococcus ovis in a patient with an artificial eye: a case report and
      literature review.
AB  - BACKGROUND: Helcococcus ovis, belonging to the genus of Helcococcu in
      Peptostreptococcaceae, is one kind of facultative anaerobic and gram-positive
      cocci, which was first isolated from a mixed infection in sheep in 1999. To our
      knowledge, it's known as an invasive pathogen in animals, and never been reported
      as a human pathogen in published literature. The aims of this work are to
      describe the first report of H. ovis which was recovered from the artificial eye
      of human case and perform a literature review. CASE PRESENTATION: A 26 year-old
      man reporting pyogenic infection with an artificial eye attended ophthalmic ward
      in Tongji hospital. After physical examination, clinical and laboratory
      investigations, the diagnosis of eye infection caused by Helcococcus ovis and
      Staphylococcus aureus was established. Receiving a medico-surgical approach, the
      patient was successfully treated. The treatment consisted in intravenous
      cefotaxime and ornidazole, levofloxacin eye drops during two weeks and removing
      of right artificial eye with debridement. CONCLUSIONS: We describe here the first
      known case of H. ovis which was recovered from human artificial eye. This report
      different from previous data found in the literature emphasizes the invasive
      potential of this bacterial species as a pathogen in human. Prospectively, the
      application of next generation sequencing tools would contribute to a more
      accurate classification of clinical strains.

PMID- 30107833
TI  - Vaginal washing and lubrication among female sex workers in the Mexico-US border
      region: implications for the development of vaginal PrEP for HIV prevention.
AB  - BACKGROUND: To assess the potential acceptability and inform the development of
      behaviorally-congruent vaginal douche- or gel-based HIV pre-exposure prophylaxis
      (PrEP) products, we examined vaginal washing and lubrication practices among
      female sex workers (FSWs) in Tijuana and Ciudad Juarez, two northern Mexico
      cities bordering the United States (US). METHODS: Two hundred and ninety-five HIV
      negative FSWs (145 Tijuana; 150 Ciudad Juarez) enrolled in a behavioral HIV
      prevention intervention trial completed surveys assessing vaginal washing and
      lubrication practices, as well as motivators and barriers to performing each
      practice. Logistic regression was used to identify potential predictors of each
      practice in the past month. RESULTS: In the past month, vaginal washing was
      performed by 56 and 22% of FSWs in Tijuana and Ciudad Juarez (p <  0.0001),
      respectively, while vaginal lubrication was performed by 64 and 45% of FSWs in
      Tijuana and Ciudad Juarez (p = 0.001), respectively. Vaginal washing was
      positively associated with living in Tijuana (adjusted odds ratio [AOR] = 4.35,
      95% confidence interval [CI]: 2.60-7.30), older age (AOR = 1.04 per year, 95% CI:
      1.01-1.06), and vaginal lubrication (AOR = 2.99, 95% CI: 1.67-5.35), while it was
      negatively associated with being born in the same state as the study site (AOR =
      0.50, 95% CI: 0.31-0.82), earning a monthly income >=3500 pesos (AOR = 0.53, 95%
      CI: 0.28-1.00), and hazardous alcohol consumption (AOR = 0.56, 95% CI: 0.33
      0.95). Vaginal lubrication was positively associated with living in Tijuana (AOR
      = 2.21, 95% CI: 1.37-3.54) and vaginal washing (AOR = 2.91, 95% CI: 1.64-5.18),
      while it was negatively associated with being born in the same state as the study
      site (AOR = 0.47, 95% CI: 0.29-0.75). CONCLUSIONS: The moderate and high
      prevalence of vaginal washing and lubrication, respectively, suggest behaviorally
      congruent, multi-purpose, vaginal douche- and gel-based PrEP products that
      simultaneously address FSWs' needs and prevent HIV infection may be acceptable to
      many FSWs along the Mexico-US border. Future product development and
      implementation should also consider the link between vaginal washing and
      lubrication to ensure existing practices do not undermine vaginal PrEP product
      effectiveness. TRIAL REGISTRATION: ClincialTrials.gov ( NCT02447484 ).

PMID- 30107838
TI  - CIDP, myasthenia gravis, and membranous glomerulonephritis - three autoimmune
      disorders in one patient: a case report.
AB  - BACKGROUND: We present a patient fulfilling the electrophysiological criteria for
      definite chronic inflammatory demyelinating polyneuropathy (CIDP), antibody
      positive myasthenia gravis (MG), and membranous glomerulonephritis (MGN)
      confirmed by biopsy. To our knowledge, this is the first case of the concomitant
      appearance of these three autoimmune diseases in a single patient. CASE
      REPRESENTATION: A 42-year-old Caucasian male presented with rapidly progressive
      gait disturbance, distal weakness of the lower extremities, ascending
      hypoesthesia, impaired fine motor skills, and beginning cranial nerve palsy
      showing dysarthrophonia, facial paralysis, and eye movement abnormalities and was
      diagnosed as rapid onset (atypical) CIDP. After 3 months, the patient complained
      of increasing physical exhaustion, reduction of his walking distance, worsening
      of the residual dysphagia, and dysarthria with an inability to swallow. AChR
      antibodies (17.0 nmol/L, RF < 0.4) and titin antibodies were positive and
      repetitive nerve stimulation showed an abnormal decrement matching the criteria
      of myasthenia gravis. Over time the patient developed severe acute-on-chronic
      renal failure with high-grade proteinuria resulting in generalized edema followed
      by secondary hyperparathyroidism and dialysis-dependent renal failure. Renal
      biopsy confirmed beginning anti-phospholipase A2 receptor antibody membranous
      nephropathy. CONCLUSION: All three diseases are of autoimmune origin with
      distinctive immunopathogenetic mechanisms. The present case of CIDP, MG, and MGN
      occurring in one patient indicates a common underlying immune mechanism in these
      distinct conditions, including the involvement of autoantibodies and T cells.

PMID- 30107837
TI  - Kv1.3 channel blockade with the Vm24 scorpion toxin attenuates the CD4+ effector
      memory T cell response to TCR stimulation.
AB  - BACKGROUND: In T cells, the Kv1.3 and the KCa3.1 potassium channels regulate the
      membrane potential and calcium homeostasis. Notably, during TEM cell activation,
      the number of Kv1.3 channels on the cell membrane dramatically increases. Kv1.3
      blockade results in inhibition of Ca2+ signaling in TEM cells, thus eliciting an
      immunomodulatory effect. Among the naturally occurring peptides, the Vm24 toxin
      from the Mexican scorpion Vaejovis mexicanus is the most potent and selective
      Kv1.3 channel blocker known, which makes it a promissory candidate for its use in
      the clinic. We have shown that addition of Vm24 to TCR-activated human T cells
      inhibits CD25 expression, cell proliferation and reduces delayed-type
      hypersensitivity reactions in a chronic inflammation model. Here, we used the
      Vm24 toxin as a tool to investigate the molecular events that follow Kv1.3
      blockade specifically on human CD4+ TEM cells as they are actively involved in
      inflammation and are key mediators of autoimmune diseases. METHODS: We combined
      cell viability, activation, and multiplex cytokine assays with a proteomic
      analysis to identify the biological processes affected by Kv1.3 blockade on
      healthy donors CD4+ TEM cells, following TCR activation in the presence or
      absence of the Vm24 toxin. RESULTS: The peptide completely blocked Kv1.3 channels
      currents without impairing TEM cell viability, and in response to TCR
      stimulation, it inhibited the expression of the activation markers CD25 and CD40L
      (but not that of CD69), as well as the secretion of the pro-inflammatory
      cytokines IFN-gamma and TNF and the anti-inflammatory cytokines IL-4, IL-5, IL-9,
      IL-10, and IL-13. These results, in combination with data from the proteomic
      analysis, indicate that the biological processes most affected by the blockade of
      Kv1.3 channels in a T cell activation context were cytokine-cytokine receptor
      interaction, mRNA processing via spliceosome, response to unfolded proteins and
      intracellular vesicle transport, targeting the cell protein synthesis machinery.
      CONCLUSIONS: The Vm24 toxin, a highly specific inhibitor of Kv1.3 channels
      allowed us to define downstream functions of the Kv1.3 channels in human CD4+ TEM
      lymphocytes. Blocking Kv1.3 channels profoundly affects the mRNA synthesis
      machinery, the unfolded protein response and the intracellular vesicle transport,
      impairing the synthesis and secretion of cytokines in response to TCR engagement,
      underscoring the role of Kv1.3 channels in regulating TEM lymphocyte function.

PMID- 30107839
TI  - Duodenal intussusception of the remnant stomach after biliopancreatic diversion:
      a case report.
AB  - BACKGROUND: We present a rare case of an antegrade intussusception of the remnant
      stomach four years after a biliopancreatic diversion. CASE PRESENTATION: A 55
      year-old female patient presented with epigastric pain in our emergency room.
      Laboratory parameters showed an anemia as well as elevated transaminases and
      hyperbilirubinemia. The CT scan showed an intussusception of the remnant stomach
      into the duodenum followed by cholestasis. At laparotomy the remnant stomach was
      resected. CONCLUSION: Bowel obstruction and intussusception after bariatric
      surgery are a rare but often unrecognized complication. Sonography as well as a
      CT scan should be performed. The exploratory laparoscopy however is the most
      valuable diagnostic tool in patients with suspected intussusception, due to the
      high rate of non-specific symptoms and misinterpreted radiographic
      investigations.

PMID- 30107840
TI  - Barriers and facilitators to humanizing birth care in Tanzania: findings from
      semi-structured interviews with midwives and obstetricians.
AB  - BACKGROUND: In Tanzania, the provision of humanized care is increasingly being
      emphasized in midwifery practice, yet studies regarding perceptions and practices
      of skilled health personnel towards the humanization of birth care are scare.
      Previous reviews have identified that abuse and disrespect is not limited to
      individuals but reflects systematic failures and deeply embedded provider
      attitudes and beliefs. Therefore, the current study aims to explore the
      perceptions and practices of skilled health personnel on humanizing birth care in
      Tanzania by identifying current barriers and facilitators. METHODS: Semi
      structured interviews were held with skilled health personnel including midwives
      (n = 6) and obstetricians (n = 2) working in the two district hospitals of
      Tanzania. Data were analyzed using thematic coding. RESULTS: Skilled health
      personnel identified systematic barriers to providing humanizing birth care.
      Systematic barriers included lack of space and limited facilities. Institutional
      norms and practices prohibited family involvement during the birth
      process,including beliefs that limited choice of birth position as well as
      disrespected beliefs, traditions, and culture. Participants also acknowledged
      four facilitators that improve the likelihood of humanized care during childbirth
      in Tanzania: ongoing education of skilled health personnel on respectful maternal
      care, institutional norms designed for continuous clinic support during
      childbirth, belief in the benefit of having family become active participants,
      and respecting maternal wishes when appropriate. CONCLUSION: To move forward with
      humanizing the birth process in Tanzania, it will be essential that systematic
      barriers are addressed as well as changing the mindset of personnel towards
      respectful maternal care. It will be essential for the government and private
      hospitals to revalue their labour wards to increase the space and staff allocated
      to each mother to enhance family-integrated care. Additionally, in-service
      training as well as incorporation of respectful maternal care during pre-service
      training is key to changing the culture in the labour ward.

PMID- 30107841
TI  - Urinary exosome miR-146a is a potential marker of albuminuria in essential
      hypertension.
AB  - BACKGROUND: There is increasing interest in using extracellular vesicle-derived
      microRNAs (miRNAs) as biomarkers in renal dysfunction and injury. Preliminary
      evidence indicates that miRNAs regulate the progression of glomerular disease.
      Indeed, exosomes from the renal system have provided novel evidence in the
      clinical setting of albuminuria. Thus, the aim of this study was to quantify the
      urinary miRNAs present in exosome and microvesicles (MVs), and to assess their
      association with the presence of increased urinary albumin excretion in essential
      hypertension. METHODS: Exosomes were collected from urine specimens from a cohort
      of hypertensive patients with (n = 24) or without albuminuria (n = 28), and from
      20 healthy volunteers as a control group. Urinary exosomes were phenotyped by
      Western blot, tunable resistive pulse sensing, and electronic microscopy.
      Expression of miR-146a and miR-335* was analysed by qRT-PCR and any associations
      between albuminuria and exosomal miRNAs were analysed. RESULTS: Urinary miRNAs
      are highly enriched in exosome subpopulations compared to MVs, both in patients
      with or without increased albuminuria (p < 0.001), but not in the control group.
      High albuminuria was associated with 2.5-fold less miR-146a in exosomes (p =
      0.017), whereas miR-146a levels in MV did not change. In addition, exosome miR
      146a levels were inversely associated with albuminuria (r = 0.65, p < 0.0001),
      and discriminated the presence of urinary albumin excretion presence [area under
      the curve = 0.80, 95% confidence interval: 0.66-0.95; p = 0.0013]. CONCLUSIONS:
      Our results indicate that miRNAs were enriched in the urinary exosome
      subpopulation in hypertensive patients and that low miR-146a expression in
      exosomes was associated with the presence of albuminuria. Thus, urinary exosome
      miR-146a may be a potentially useful tool for studying early renal injury in
      hypertension.

PMID- 30107842
TI  - QsRNA-seq: a method for high-throughput profiling and quantifying small RNAs.
AB  - The ability to profile and quantify small non-coding RNAs (sRNAs), specifically
      microRNAs (miRNAs), using high-throughput sequencing is challenging because of
      their small size. We developed QsRNA-seq, a method for preparation of sRNA
      libraries for high-throughput sequencing that overcomes this difficulty by
      enabling a gel-free separation of fragments shorter than 100 nt that differ only
      by 20 nt in length. The method allows the use of unique molecular identifiers for
      quantification and is more amenable to automation than gel-based methods. We show
      that QsRNA-seq gives very accurate, comprehensive, and reproducible results by
      looking at miRNAs in Caenorhabditis elegans embryos and larvae.

PMID- 30107844
TI  - Long term trends in behaviour to protect against adverse reproductive and sexual
      health outcomes among young single African women.
AB  - BACKGROUND: HIV and unintended pregnancy are major interrelated concerns in sub
      Saharan Africa. Focussing on single women aged 15-24 years we assess trends in
      key behaviours that affect both outcomes. METHODS: We performed a secondary
      analysis of public-access data sets from 112 surveys from 36 countries in the
      region, conducted between 1991 and 2015. We examined trends over 20 years in
      primary abstinence (virginity), secondary abstinence (no sex in past 3 months)
      among sexually experienced women, current use of modern contraception and condom
      use at most recent coitus among sexually active women. RESULTS: Little change
      occurred in primary or secondary abstinence. Over the 20 year period,
      contraceptive use in the region rose from 14.7 to 33.4%, with significant
      increases observed in 18 of 30 countries with multiple surveys. Since 2001-2005,
      the proportion of contraceptive users reporting condoms as their method fell from
      61.1 to 51.3%, while use of oral contraceptives or injectables rose from 19.9 to
      24.0%. Between 1996 and 2000 and 2006-2010, condom use at last coitus rose from
      21.3 to 40.5% but then plateaued. A strong correlation between condom use and
      national HIV prevalence was found. About half of condom users at last sex had
      earlier in interviews reported this method for pregnancy-prevention. CONCLUSIONS:
      Though condoms tend to be overlooked by both HIV and family planning agencies,
      their contribution to the health of single women remains central. Current efforts
      to promote non-barrier contraceptive methods may inadvertently increase HIV risk.
      Condom promotion for pregnancy-prevention should be re-invigorated by social
      marketing campaigns and other means.

PMID- 30107843
TI  - Study protocol of "Our Choice": a randomized controlled trial of the integration
      of safer conception counseling to transform HIV family planning services in
      Uganda.
AB  - BACKGROUND: About 40% of HIV-positive women in sub-Saharan Africa become pregnant
      post-diagnosis. Despite about half of their pregnancies being planned, safer
      conception methods (SCM) are underutilized among serodiscordant couples,
      partially due to the fact that safer conception counseling (SCC) has not been
      integrated into routine HIV family planning (FP) services. METHODS: Our Choice is
      a comprehensive FP intervention that promotes unbiased childbearing consultations
      to ensure clients receive SCC or contraception services to achieve their desired
      reproductive goals. The intervention is theoretically grounded and has
      demonstrated preliminarily feasibility and acceptance through pilot testing. This
      three-arm cluster randomized controlled trial compares two implementation
      strategies for integrating Our Choice into routine FP services vs. usual care.
      Six sites in Uganda will be randomized to receive either (1) Our Choice
      intervention with enhanced training and supervision provided by study staff
      (SCC1), (2) Our Choice intervention implemented by the Ministry of Health's
      standard approach to disseminating new services (SCC2), or (3) existing FP
      services (usual care). Our Choice and usual care FP services will be implemented
      simultaneously over a 30-month period. Sixty clients in serodiscordant
      relationships who express childbearing desires will be enrolled by a study
      coordinator at each site (n = 360) and followed for 12 months or post-pregnancy
      (once, if applicable). Analysis will compare intervention arms (SCC1 and SCC2) to
      usual care and then to each other (SCC1 vs. SCC2) on the primary outcome of
      correct use of either SCM (if trying to conceive) or dual contraception (if
      pregnancy is not desired). Secondary outcomes (i.e., pregnancy, use of prevention
      of mother-to-child transmission services, condom use, and partner seroconversion)
      and cost-effectiveness will also be examined. DISCUSSION: Findings will provide
      critical information about the success of implementation models of varying
      intensity for integrating SCC into FP, thereby informing policy and resource
      allocation within and beyond Uganda. TRIAL REGISTRATION: NCT03167879
      ClinicalTrials.gov, Registered 30 May, 2017.

PMID- 30107845
TI  - The efficacy and adverse events of mTOR inhibitors in lymphangioleiomyomatosis:
      systematic review and meta-analysis.
AB  - BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare lung disease and the
      mammalian target of the rapamycin (mTOR) inhibitors has been used as an effective
      therapy. Here we conducted a systematic review and meta-analysis with the aims to
      quantify the efficacy and safety of mTOR inhibitors in LAM patients. METHODS: The
      following databases were searched for clinical trials regarding LAM patients
      treated with mTOR inhibitors until December 2017: Pubmed, Embase, Cochrane
      Library and OVID medicine. Random effect models were used for the quantitative
      analysis. RESULTS: Nine eligible studies were included in our systematic review,
      7 of which were used for the meta-analysis. In LAM patients, mTOR inhibitors
      improved forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)
      significantly, with the weighted mean difference (WMD) 0.15 L (95%CI: 0.08 to
      0.22, P < 0.01, I2 = 0%) and 0.22 L (95%: 0.11 to 0.32, P < 0.01, I2 = 0%)
      respectively. There was no significant change in neither the diffusing capacity
      for carbon monoxide (WMD: 0.51 ml/mm Hg/min, 95%CI: -0.48 to 1.49, P = 0.31, I2 =
      0%) nor 6-min walking distance (WMD: 5.29 m, 95%CI: -18.01 to 28.59, P = 0.66, I2
      = 1%). The weighted partial response rate was 0.68 (95%CI: 0.53 to 0.84, P <
      0.01, I2 = 72%) for renal angiomylipoma. The cumulative incidence rates of common
      safety events were 50, 40, 23, 20 and 19% for oral mucositis, hyperlipidemia,
      headache, bone marrow suppression, and diarrhea, respectively. And most events
      were low grade and tolerant. CONCLUSIONS: In LAM patients, there are improvements
      of FEV1 and FVC after the application of mTOR inhibitors and over a half achieved
      the shrinkage of renal angiomyolipoma. TRIAL REGISTRATION: PROSPERO registration
      number: CRD42018085470. Registered 22 January 2018.

PMID- 30107846
TI  - The clinical spectrum and genetic variability of limb-girdle muscular dystrophy
      in a cohort of Chinese patients.
AB  - BACKGROUND: Limb-girdle muscular dystrophy (LGMD) is a commonly diagnosed
      hereditary muscular disorder, characterized by the progressive weakness of the
      limb-girdle muscles. Although the condition has been well-characterized, clinical
      and genetic heterogeneity can be observed in patients with LGMD. Here, we aimed
      to describe the clinical manifestations and genetic variability among a cohort of
      patients with LGMD in South China. RESULTS: We analyzed the clinical information,
      muscle magnetic resonance imaging (MRI) findings, and genetic results obtained
      from 30 patients (24 families) with clinically suspected LGMD. In 24 probands, 38
      variants were found in total, of which 18 were shown to be novel. Among the 30
      patients, the most common subtypes were dysferlinopathy in eight (26.67%),
      sarcoglycanopathies in eight [26.67%; LGMD 2C in three (10.00%), LGMD 2D in three
      (10.00%), and LGMD 2F in two (6.67%)], LGMD 2A in seven (23.33%), followed by
      LGMD 1B in three (10.00%), LGMD 2I in three (10.00%), and early onset recessive
      Emery-Dreifuss-like phenotype without cardiomyopathy in one (3.33%). Furthermore,
      we also observed novel clinical presentations for LGMD 1B, 2F, and 2I patients
      with hypermobility of the joints in the upper limbs, a LGMD 2F patient with
      delayed language development, and other manifestations. Moreover, distinct
      distributions of fatty infiltration in patients with LGMD 2A, dysferlinopathy,
      and the early onset recessive Emery-Dreifuss-like phenotype without
      cardiomyopathy were also observed based on muscle MRI results. CONCLUSIONS: In
      this study, we expanded the clinical spectrum and genetic variability found in
      patients with LGMD, which provided additional insights into genotype and
      phenotype correlations in this disease.

PMID- 30107847
TI  - Fibrin glue pleurodesis for pneumothorax in extremely preterm infants: a case
      report and literature review.
AB  - BACKGROUND: Chest tube drainage and mechanical ventilation are effective
      treatment of symptomatic pneumothorax (PTX), but the best management of
      persistent (> 7 days) PTX is unknown. CASE PRESENTATION: We reported a case of
      successful fibrin glue pleurodesis of persistent PTX in an extremely preterm
      infant without adverse effects. We discussed previous literature on this
      treatment. CONCLUSIONS: Overall, the twelve reported cases suggest that
      persistent PTX sealing with fibrin glue can represent a simple, quick, and
      effective treatment whose possible reported adverse effects are transient and do
      not cause permanent sequelae. Thus, fibrin glue pleurodesis might be considered a
      suitable therapeutic tool in very preterm infant with persistent PTX.

PMID- 30107848
TI  - Neuroprotection and immunomodulation following intraspinal axotomy of motoneurons
      by treatment with adult mesenchymal stem cells.
AB  - BACKGROUND: Treatment of spinal cord injury is dependent on neuronal survival,
      appropriate synaptic circuit preservation, and inflammatory environment
      management. In this sense, mesenchymal stem cell (MSC) therapy is a promising
      tool that can reduce glial reaction and provide trophic factors to lesioned
      neurons. METHODS: Lewis adult female rats were submitted to a unilateral ventral
      funiculus cut at the spinal levels L4, L5, and L6. The animals were divided into
      the following groups: IA (intramedullary axotomy), IA + DMEM (Dulbecco's modified
      Eagle's medium), IA + FS (fibrin sealant), IA + MSC (106 cells), and IA + FS +
      MSC (106 cells). Seven days after injury, qPCR (n = 5) was performed to assess
      gene expression of VEGF, BDNF, iNOS2, arginase-1, TNF-alpha, IL-1beta, IL-6, IL
      10, IL-4, IL-13, and TGF-beta. The cellular infiltrate at the lesion site was
      analyzed by hematoxylin-eosin (HE) staining and immunohistochemistry (IH) for
      Iba1 (microglia and macrophage marker) and arginase-1. Fourteen days after
      injury, spinal alpha motor neurons (MNs), evidenced by Nissl staining (n = 5),
      were counted. For the analysis of astrogliosis in spinal lamina IX and synaptic
      detachment around lesioned motor neurons (GAP-43-positive cells), anti-GFAP and
      anti-synaptophysin immunohistochemistry (n = 5) was performed, respectively.
      Twenty-eight days after IA, the gait of the animals was evaluated by the walking
      track test (CatWalk; n = 7). RESULTS: The site of injury displayed strong
      monocyte infiltration, containing arginase-1-expressing macrophages. The FS
      treated group showed upregulation of iNOS2, arginase-1, proinflammatory cytokine
      (TNF-alpha and IL-1beta), and antiinflammatory cytokine (IL-10, IL-4, and IL-13)
      expression. Thus, FS enhanced early macrophage recruitment and proinflammatory
      cytokine expression, which accelerated inflammation. Rats treated with MSCs
      displayed high BDNF-positive immunolabeling, suggesting local delivery of this
      neurotrophin to lesioned motoneurons. This BDNF expression may have contributed
      to the increased neuronal survival and synapse preservation and decreased
      astrogliosis observed 14 days after injury. At 28 days after lesion, gait
      recovery was significantly improved in MSC-treated animals compared to that in
      the other groups. CONCLUSIONS: Overall, the present data demonstrate that MSC
      therapy is neuroprotective and, when associated with a FS, shifts the immune
      response to a proinflammatory profile.

PMID- 30107850
TI  - Enhanced effect of checkpoint inhibitors when given after or together with IMM
      101: significant responses in four advanced melanoma patients with no additional
      major toxicity.
AB  - BACKGROUND: The use of checkpoint inhibitors (ipilimumab, pembrolizumab,
      nivolumab) has revolutionised the treatment of metastatic melanoma. However still
      more than the half the patients do not respond to single-agent immunotherapy.
      This has led to the development of combining these agents in an attempt to
      enhance the anti-cancer activity. More than 300 different studies with 15
      different drug doses are currently ongoing. Combining different checkpoint
      inhibitors (CPIs) does indeed lead to an increase in response rate, but this is
      associated with significant toxicity. IMM-101 is a heat killed Mycobacterium
      preparation which induces marked immune modulation and little systemic toxicity.
      It has been reported as having activity in melanoma as single agent and in
      pancreatic cancer in combination with gemcitabine, the latter in a randomised
      study. METHODS: Here we report the effect of adding CPIs to 3 patients who had
      previously been on IMM-101, either as a trial or a named patient programme and a
      patient who received the IMM-101 together with nivolumab. RESULTS: All 4 patients
      had rapid and very good responses, three of them maintained over 18 months with
      no significant additional toxicity. CONCLUSIONS: The rapid and complete clinical
      responses seen in these patients may suggest that IMM-101 is activating a
      complementary pathway which is synergistic with CPI treatment.

PMID- 30107851
TI  - Localization of cassava brown streak virus in Nicotiana rustica and cassava
      Manihot esculenta (Crantz) using RNAscope(r) in situ hybridization.
AB  - BACKGROUND: Cassava brown streak disease (CBSD) has a viral aetiology and is
      caused by viruses belonging to the genus Ipomovirus (family Potyviridae), Cassava
      brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV).
      Molecular and serological methods are available for detection, discrimination and
      quantification of cassava brown streak viruses (CBSVs) in infected plants.
      However, precise determination of the viral RNA localization in infected host
      tissues is still not possible pending appropriate methods. RESULTS: We have
      developed an in situ hybridization (ISH) assay based on RNAscope(r) technology
      that allows the sensitive detection and localization of CBSV RNA in plant
      tissues. The method was initially developed in the experimental host Nicotiana
      rustica and was then further adapted to cassava. Highly sensitive and specific
      detection of CBSV RNA was achieved without background and hybridization signals
      in sections prepared from non-infected tissues. The tissue tropism of CBSV RNAs
      appeared different between N. rustica and cassava. CONCLUSIONS: This study
      provides a robust method for CBSV detection in the experimental host and in
      cassava. The protocol will be used to study CBSV tropism in various cassava
      genotypes, as well as CBSVs/cassava interactions in single and mixed infections.

PMID- 30107849
TI  - Designing robot-assisted neurorehabilitation strategies for people with both HIV
      and stroke.
AB  - There is increasing evidence that HIV is an independent risk factor for stroke,
      resulting in an emerging population of people living with both HIV and stroke all
      over the world. However, neurorehabilitation strategies for the HIV-stroke
      population are distinctly lacking, which poses an enormous global health
      challenge. In order to address this gap, a better understanding of the HIV-stroke
      population is needed, as well as potential approaches to design effective
      neurorehabilitation strategies for this population. This review goes into the
      mechanisms, manifestations, and treatment options of neurologic injury in stroke
      and HIV, the additional challenges posed by the HIV-stroke population, and
      rehabilitation engineering approaches for both high and low resource areas. The
      aim of this review is to connect the underlying neurologic properties in both HIV
      and stroke to rehabilitation engineering. It reviews what is currently known
      about the association between HIV and stroke and gaps in current treatment
      strategies for the HIV-stroke population. We highlight relevant current areas of
      research that can help advance neurorehabilitation strategies specifically for
      the HIV-stroke population. We then explore how robot-assisted rehabilitation
      combined with community-based rehabilitation could be used as a potential
      approach to meet the challenges posed by the HIV-stroke population. We include
      some of our own work exploring a community-based robotic rehabilitation exercise
      system. The most relevant strategies will be ones that not only take into account
      the individual status of the patient but also the cultural and economic
      considerations of their respective environment.

PMID- 30107852
TI  - Coexistence of medullary thyroid carcinoma and recurrent non-functional pituitary
      adenoma: a case report.
AB  - BACKGROUND: Medullary thyroid carcinoma and pituitary adenoma are neuroendocrine
      tumors and their coexistence has not been reported in the literature, previously.
      Medullary thyroid carcinoma is a neoplasm of the thyroid gland arising from
      parafollicular c-cells producing calcitonin, and pituitary adenoma is a benign
      hyperplasia of the cells of the pituitary gland. Coexistence of these neoplasms
      can be explained by being affected by simultaneous primary neoplasms or tumor-to
      tumor metastasis phenomenon. CASE PRESENTATION: We present the case of a 60-year
      old Persian man who presented to the clinic with a chief complaint of headache
      for the last 2 months. His past medical history was significant for non
      functional pituitary macroadenoma and medullary thyroid carcinoma and he had
      received a total thyroidectomy and a transsphenoidal surgery several years ago.
      Diagnostic evaluations revealed that the pituitary adenoma has recurred. He was
      well and symptom-free after the second transsphenoidal surgery for resection of
      the adenoma. Noticeably, investigations were negative for any form of multiple
      endocrine neoplasia syndromes; however, we could not rule them out definitively.
      CONCLUSIONS: To the best of our knowledge, it is the first case reported in the
      literature of a patient who has been affected by recurrent non-functional
      pituitary adenoma and medullary thyroid carcinoma, concomitantly. Although this
      association can be accidental, it emphasizes the fact that patients with a
      history of a neoplasm should be monitored regularly in order to diagnose and
      treat possible second primary cancers in a timely manner. Of note, this
      consideration is of great importance in patients whose first neoplasms have
      better prognosis and survival rates, which provide them more time to develop
      second primary cancers, for example, pituitary adenoma.

PMID- 30107853
TI  - CRISPR-SKIP: programmable gene splicing with single base editors.
AB  - CRISPR gene editing has revolutionized biomedicine and biotechnology by providing
      a simple means to engineer genes through targeted double-strand breaks in the
      genomic DNA of living cells. However, given the stochasticity of cellular DNA
      repair mechanisms and the potential for off-target mutations, technologies
      capable of introducing targeted changes with increased precision, such as single
      base editors, are preferred. We present a versatile method termed CRISPR-SKIP
      that utilizes cytidine deaminase single-base editors to program exon skipping by
      mutating target DNA bases within splice acceptor sites. Given its simplicity and
      precision, CRISPR-SKIP will be broadly applicable in gene therapy and synthetic
      biology.

PMID- 30107854
TI  - Inhibition of mTORC1 signaling protects kidney from irradiation-induced toxicity
      via accelerating recovery of renal stem-like cells.
AB  - BACKGROUND: Irradiation-induced kidney damage is inevitable during
      radiotherapeutic practice, which limits effective radiotherapy doses on tumor
      treatment. In the present study, the role of mTOR complex 1 (mTORC1) signaling
      was investigated in irradiation-induced renal injuries. METHODS: Mice were
      exposed to 8.0-Gy X-ray of total body irradiation and subsequently treated with
      rapamycin. Changes of renal morphology were assessed by hematoxylin and eosin
      staining. Expression of pS6 and CD133 was detected via immunostaining. Cellular
      apoptosis and proliferation were measured by TUNEL, caspase-3 and BrdU staining.
      Activation of mTORC1, TGF-beta and NF-kappaB signaling pathways was determined
      through western blot analysis. RESULTS: Our data displayed that irradiation
      disrupted the structures of renal corpuscles and tubules and decreased the
      density of CD133+ renal stem-like cells, which were related with increasing
      cellular apoptosis and decreasing cell proliferation post exposure. Activation of
      mTORC1, TGF-beta and NF-kappaB signaling pathways was determined in irradiated
      renal tissues, which were inhibited by rapamycin treatment. Application of
      rapamycin after irradiation decreased cellular apoptosis and increased autophagy
      and cell proliferation in renal tissues. The density of CD133+ renal stem-like
      cells was significantly increased in irradiated kidneys after rapamycin
      treatment. The morphology of irradiated renal corpuscles and tubules was
      gradually recovered upon rapamycin treatment. CONCLUSIONS: These findings
      indicate that inhibition of mTORC1 signaling by rapamycin ameliorates irradiation
      induced renal toxicity mediated by decreasing cellular apoptosis and increasing
      CD133+ renal stem-like cells.

PMID- 30107855
TI  - Undertriage of major trauma patients at a university hospital: a retrospective
      cohort study.
AB  - BACKGROUND: Studies show increased mortality among severely injured patients not
      met by trauma team. Proper triage is important to ensure that all severely
      injured patients receive vital trauma care. In 2017 a new national trauma plan
      was implemented in Norway, which recommended the use of a modified version of
      "Guidelines for Field Triage of Injured Patients" to identify severely injured
      patients. METHODS: A retrospective study of 30,444 patients admitted to Haukeland
      University Hospital in 2013, with ICD-10 injury codes upon discharge. The
      exclusion criteria were department affiliation considered irrelevant when
      identifying trauma, patients with injuries that resulted in Injury Severity Score
      < 15, patients that did receive trauma team, and patients admitted > 24 h after
      time of injury. Information from patient records of every severely injured
      patient admitted in 2013 was obtained in order to investigate the sensitivity of
      the new guidelines. RESULTS: Trauma team activation was performed in 369
      admissions and 85 patients were identified as major trauma. Ten severely injured
      patients did not receive trauma team resuscitation, resulting in an undertriage
      of 10.5%. Nine out of ten patients were men, median age 54 years. Five patients
      were 60 years or older. All of the undertriaged patients experienced fall from
      low height (< 4 m). Traumatic brain injury was seen in six patients. Six patients
      had a Glasgow Coma Scale score <= 13. The new trauma activation guidelines had a
      sensitivity of 95.0% in our 2013 trauma population. The degree of undertriage
      could have been reduced to 4.0% had the guidelines been implemented and correctly
      applied. CONCLUSIONS: The rate of undertriage at Haukeland University Hospital in
      2013 was above the recommendations of less than 5%. Use of the new trauma
      guidelines showed increased triage precision in the present trauma population.

PMID- 30107856
TI  - Membrane binding, internalization, and sorting of alpha-synuclein in the cell.
AB  - Alpha-synuclein (aSyn) plays a crucial role in Parkinson's disease (PD) and other
      synucleinopathies, since it misfolds and accumulates in typical proteinaceous
      inclusions. While the function of aSyn is thought to be related to vesicle
      binding and trafficking, the precise molecular mechanisms linking aSyn with
      synucleinopathies are still obscure. aSyn can spread in a prion-like manner
      between interconnected neurons, contributing to the propagation of the pathology
      and to the progressive nature of synucleinopathies. Here, we investigated the
      interaction of aSyn with membranes and trafficking machinery pathways using
      cellular models of PD that are amenable to detailed molecular analyses. We found
      that different species of aSyn can enter cells and form high molecular weight
      species, and that membrane binding properties are important for the
      internalization of aSyn. Once internalized, aSyn accumulates in intracellular
      inclusions. Interestingly, we found that internalization is blocked in the
      presence of dynamin inhibitors (blocked membrane scission), suggesting the
      involvement of the endocytic pathway in the internalization of aSyn. By screening
      a pool of small Rab-GTPase proteins (Rabs) which regulate membrane trafficking,
      we found that internalized aSyn partially colocalized with Rab5A and Rab7.
      Initially, aSyn accumulated in Rab4A-labelled vesicles and, at later stages, it
      reached the autophagy-lysosomal pathway (ALP) where it gets degraded. In total,
      our study emphasizes the importance of membrane binding, not only as part of the
      normal function but also as an important step in the internalization and
      subsequent accumulation of aSyn. Importantly, we identified a fundamental role
      for Rab proteins in the modulation of aSyn processing, clearance and spreading,
      suggesting that targeting Rab proteins may hold important therapeutic value in PD
      and other synucleinopathies.

PMID- 30107857
TI  - Rabies virus transmission via solid organs or tissue allotransplantation.
AB  - BACKGROUND: Rabies, for which the mortality rate is almost 100%, is a zoonotic
      viral disease that can be transmitted via solid organs or tissue
      allotransplantation. Dozens of deaths from rabies via solid organs or tissues
      allotransplantation (ROTA) have been documented during the last decades. In 2015
      and 2016, two cases of rabies virus transmission via solid organs or tissue
      allotransplantation were reported in China, which further underscore the risk and
      importance of this special type of rabies for organ transplant recipients. MAIN
      TEXT: From 1978 to 2017, at least 13 cases of ROTA, causing dozens of deaths,
      have been reported worldwide, whether in the high-risk or low-risk countries of
      rabies. The reported incubation period of ROTA ranges from 11 days to more than
      17 months, while the historical incubation period of rabies is generally
      considered to range from ~ 1 week to several years. The pathogenesis of ROTA is
      not clear, but the use of post-exposure prophylaxis (PEP) can play a protective
      role in the transplant recipients. We also summarize reports about ROTA in China,
      combined with the actual situation regarding work on rabies surveillance and
      elimination, and suggest countermeasures for the prevention and control of ROTA
      in the future. CONCLUSIONS: Understanding the significance of ROTA, screening the
      suspected organs, assessing the risk and protecting the related population will
      be effective way to prevent and control further occurrence of ROTA.

PMID- 30107858
TI  - Whole-body magnetic resonance imaging of Li-Fraumeni syndrome patients:
      observations from a two rounds screening of Brazilian patients.
AB  - BACKGROUND: Li-Fraumeni syndrome (LFS) is an autosomal dominant disease that is
      associated with germline TP53 mutations and it predisposes affected individuals
      to a high risk of developing multiple tumors. In Brazil, LFS is characterized by
      a different pattern of TP53 variants, with the founder TP53 p.R337H mutation
      being predominant. The adoption of screening strategies to diagnose LFS in its
      early stages is a major challenge due to the diverse spectrum of tumors that LFS
      patients can develop. The purpose of this study was to evaluate two rounds of
      whole-body magnetic resonance imaging (WB-MRI) which were conducted as a
      screening strategy for LFS patients. METHODS: Over a 4-year period, 59 LFS
      patients underwent two rounds of WB-MRI. Each MRI was characterized as positive
      or negative, and positive cases were further investigated to establish a
      diagnosis. The parameters used to evaluate the WB-MRI results included: positive
      rate, number of invasive investigations of positive results, and cancer detection
      rate. RESULTS: A total of 118 WB-MRI scans were performed. Positive results were
      associated with 11 patients (9.3%). Seven of these patients (11.8%) were
      identified in the first round of screening and 4 patients (6.7%) were identified
      in the second round of screening. Biopsies were performed in three cases (2.5%),
      two (3.4%) after the first round of screening and one (1.7%) after the second
      round of screening. The histopathological results confirmed a diagnosis of cancer
      for all three cases. There was no indication of unnecessary invasive procedures.
      CONCLUSIONS: WB-MRI screening of LFS carriers diagnosed cancers in their early
      stages. When needed, positive results were further examined with non-invasive
      imaging techniques. False positive results were less frequent after the first
      round of WB-MRI screening.

PMID- 30107862
TI  - Exploration of the influence of insecure attachment and parental maltreatment on
      the incidence and course of adult clinical depression.
AB  - BACKGROUND: Both childhood maltreatment and insecure attachment are known to be
      associated with depression in adulthood. The extent insecure attachment increases
      the risk of adult clinical depression over that of parental maltreatment among
      women in the general population is explored, using those at high risk because of
      their selection for parental maltreatment together with an unselected sample.
      METHODS: Semi-structured interviews and investigator-based measures are employed.
      RESULTS: Insecure attachment is highly associated with parental maltreatment with
      both contributing to the risk of depression, with attachment making a substantial
      independent contribution. Risk of depression did not vary by type of insecure
      attachment, but the core pathways of the dismissive and enmeshed involved the
      whole life course in terms of greater experience of a mother's physical abuse and
      their own anger as an adult, with both related to adult depression being more
      often provoked by a severely threatening event involving humiliation rather than
      loss. By contrast, depression of the insecure fearful and withdrawn was more
      closely associated with both current low self-esteem and an inadequately
      supportive core relationship. In terms of depression taking a chronic course,
      insecure attachment was again a key risk factor, but with this now closely linked
      with the early experience of a chaotic life style but with this involving only a
      modest number of women. CONCLUSIONS: Both insecure attachment and parental
      maltreatment contribute to an increased risk of depression with complex effects
      involving types of insecure attachment.

PMID- 30107859
TI  - Photoperiodic diapause in a subtropical population of Aedes albopictus in
      Guangzhou, China: optimized field-laboratory-based study and statistical models
      for comprehensive characterization.
AB  - BACKGROUND: Aedes albopictus is among the 100 most invasive species worldwide and
      poses a major risk to public health. Photoperiodic diapause provides a crucial
      ecological basis for the adaptation of this species to adverse environments. Ae.
      albopictus is the vital vector transmitting dengue virus in Guangzhou, but its
      diapause activities herein remain obscure. METHODS: In the laboratory, yeast
      powder and food slurry were compared for a proper diapause determination method,
      and the critical photoperiod (CPP) was tested at illumination times of 11, 11.5,
      12, 12.5, 13, and 13.5 h. A 4-parameter logistic (4PL) regression model was
      selected to estimate the CPP. In the field, the seasonal dynamics of the Ae.
      albopictus population, egg diapause, and hatching of overwintering eggs were
      investigated monthly, weekly, and daily, respectively. A distributed lag non
      linear model (DLNM) was used to assess the associations of diapause with
      meteorological factors. RESULTS: In the laboratory, both the wild population and
      the Foshan strain of Ae. albopictus were induced to diapause at an incidence
      greater than 80%, and no significant difference (P > 0.1) was observed between
      the two methods for identifying diapause. The CPP of this population was
      estimated to be 12.312 h of light. In the field, all of the indexes of the wild
      population were at the lowest levels from December to February, and the Route
      Index was the first to increase in March. Diapause incidence displayed pronounced
      seasonal dynamics. It was estimated that the day lengths of 12.111 h at week2016,
      43 and 12.373 h at week2017, 41 contributed to diapause in 50% of the eggs. Day
      length was estimated to be the main meteorological factor related to diapause.
      CONCLUSIONS: Photoperiodic diapause of Ae. albopictus in Guangzhou of China was
      confirmed and comprehensively elucidated in both the laboratory and the field.
      Diapause eggs are the main form for overwintering and begin to hatch in large
      quantities in March in Guangzhou. Furthermore, this study also established an
      optimized investigation system and statistical models for the study of Ae.
      albopictus diapause. These findings will contribute to the prevention and control
      of Ae. albopictus and mosquito-borne diseases.

PMID- 30107861
TI  - Levels and correlates of nutritional status of women of childbearing age in rural
      Bangladesh.
AB  - OBJECTIVE: The present study examined the prevalence of and risk factors for
      malnutrition in a population-based cohort of women of childbearing age in rural
      Bangladesh. DESIGN: A cross-sectional study that collected pre-pregnancy weight,
      height, and data on selected risk factors for nutritional status of women.
      SETTING: The study was conducted in Sylhet District of Bangladesh. SUBJECTS:
      Study subjects included 13 230 non-pregnant women of childbearing age. Women were
      classified into underweight (<18.5 kg/m2), normal (18.5-24.9 kg/m2) and
      overweight/obese (>=25.0 kg/m2) using BMI; and into moderate to severe stunting
      (<150 cm), mild stunting (150-<155 cm) and normal (>=155 cm) using height. Two
      multinomial logistic regression models were fitted for BMI: model 1 examined
      individual and household factors associated with BMI, and model 2 additionally
      examined the association of community variables. The same analysis was conducted
      for height. RESULTS: Prevalence of underweight, overweight/obesity and moderate
      to severe stunting was 37.0, 7.2 and 48.6 %, respectively. Women's education and
      household wealth were inversely related to both underweight status and stunting.
      Underweight rate was significantly lower in the post-harvest season. Women with
      any education and who belonged to households with higher wealth were more likely
      to be overweight/obese. CONCLUSIONS: The study documented high underweight and
      stunting, and moderate overweight/obesity rates among rural Bangladeshi women;
      and recommends design and implementation of a multidimensional intervention
      programme based on individual-, household- and community-level risk factors that
      can address underweight, stunting and overweight/obesity to improve the
      nutritional status of women of childbearing age in Bangladesh.

PMID- 30107863
TI  - Water intake from foods and beverages and risk of mortality from CVD: the Japan
      Collaborative Cohort (JACC) Study.
AB  - OBJECTIVE: To examine the association of water intake with risk of mortality from
      CVD. DESIGN: Prospective cohort study.Setting/SubjectsA total of 22 939 men and
      35 362 women aged 40-79 years enrolled in the Japan Collaborative Cohort (JACC)
      Study with available data regarding water intake from foods and beverages. The
      underlying causes of death were determined based on the International
      Classification of Diseases. RESULTS: During the median 19.1 years of follow-up,
      1637 men and 1707 women died from CVD. There was an inverse trend between high
      water intake and risk of CVD in both sexes. Compared with participants in the
      lowest quintile of water intake, the multivariable-adjusted hazard ratios (95 %
      CI) for mortality from total CVD in the highest quintile of water intake were
      0.88 (0.72, 1.07; P for trend=0.03) in men and 0.79 (0.66, 0.95; P for
      trend=0.10) in women. Those for CHD were 0.81 (0.54, 1.21; P for trend=0.06) in
      men and 0.60 (0.39, 0.93; P for trend=0.20) in women. Reduced risk of mortality
      from ischaemic stroke was also observed among women in the highest water intake
      quintile: 0.70 (0.47, 0.99; P for trend=0.19). There was no association between
      water intake and mortality from haemorrhagic stroke in either sex. CONCLUSIONS:
      Higher intake of fluids from foods and beverages was associated with reduced risk
      of cardiovascular mortality in both sexes and reduced risk of ischaemic stroke in
      women in Japan.

PMID- 30107860
TI  - Therapeutic potential of stromal cells of non-renal or renal origin in
      experimental chronic kidney disease.
AB  - BACKGROUND: Mesenchymal stromal cell (MSC)-based therapy is a promising strategy
      for preventing the progression of chronic kidney disease (CKD), with the
      potential to induce tissue regeneration. In search of the best cellular source we
      compared, in the rat model of adriamycin (ADR) nephropathy, the regenerative
      potential of human stromal cells of non-renal origin, such as bone marrow (bm)
      MSCs and umbilical cord (uc) MSCs, with that of newly discovered stromal cells of
      renal origin, the kidney perivascular cells (kPSCs) known to exhibit tissue
      specific properties. METHODS: The therapeutic effect of repeated infusions of
      human bmMSCs, ucMSCs, kPSCs (1.5 * 106 cells/rats) or conditioned medium from
      ucMSCs was studied in athymic rats with ADR-induced nephropathy (7.9 mg/kg). The
      ability of the three stromal cell populations to engraft the damaged kidney was
      evaluated by detecting the presence of human nuclear antigenpos cells. Glomerular
      podocyte loss and endothelial damage, sclerotic lesions and inflammation were
      assessed at 14 and 28 days. In-vitro experiments with a transwell system were
      performed to investigate the effects of different stromal cell populations on
      parietal epithelial cells (PECs) activated or not with albumin or angiotensin II
      for 24 h. RESULTS: Infusions of non-renal and renal stromal cells resulted in a
      comparable engraftment into the kidney, in the peritubular areas and around the
      glomerular structures. All three cell populations limited podocyte loss and
      glomerular endothelial cell injury, and attenuated the formation of podocyte and
      PEC bridges. This translated into a reduction of glomerulosclerosis and fibrosis.
      Human ucMSCs had an anti-inflammatory effect superior to that of the other
      stromal cells, reducing macrophage infiltration and inducing polarisation towards
      the M2 macrophage phenotype. Conditioned medium from ucMSCs shared the same
      renoprotective effects of the cells. Consistent with in-vivo data, bmMSCs and
      kPSCs, but even more so ucMSCs, limited proliferation, migratory potential and
      extracellular matrix production of activated PECs, when cultured in a transwell
      system. CONCLUSIONS: Our data indicate that either non-renal or renal stromal
      cells induce renal tissue repair, highlighting ucMSCs and their conditioned
      medium as the most reliable clinical therapeutic tool for CKD patients.

PMID- 30107864
TI  - Prevalence of pre-stroke depression and its association with post-stroke
      depression: a systematic review and meta-analysis.
AB  - BACKGROUND: Depression is a common post-stroke complication. Pre-stroke
      depression may be an important contributor, however the epidemiology of pre
      stroke depression is poorly understood. Using systematic review and meta
      analysis, we described the prevalence of pre-stroke depression and its
      association with post-stroke depression. METHODS: We searched multiple cross
      disciplinary databases from inception to July 2017 and extracted data on the
      prevalence of pre-stroke depression and its association with post-stroke
      depression. We assessed the risk of bias (RoB) using validated tools. We
      described summary estimates of prevalence and summary odds ratio (OR) for
      association with post-stroke depression, using random-effects models. We
      performed subgroup analysis describing the effect of depression assessment
      method. We used a funnel plot to describe potential publication bias. The
      strength of evidence presented in this review was summarised via 'GRADE'.
      RESULTS: Of 11 884 studies identified, 29 were included (total participants n =
      164 993). Pre-stroke depression pooled prevalence was 11.6% [95% confidence
      interval (CI) 9.2-14.7]; range: 0.4-24% (I2 95.8). Prevalence of pre-stroke
      depression varied by assessment method (p = 0.02) with clinical interview
      suggesting greater pre-stroke depression prevalence (~17%) than case-note review
      (9%) or self-report (11%). Pre-stroke depression was associated with increased
      odds of post-stroke depression; summary OR 3.0 (95% CI 2.3-4.0). All studies were
      judged to be at RoB: 59% of included studies had an uncertain RoB in stroke
      assessment; 83% had high or uncertain RoB for pre-stroke depression assessment.
      Funnel plot indicated no risk of publication bias. The strength of evidence based
      on GRADE was 'very low'. CONCLUSIONS: One in six stroke patients have had pre
      stroke depression. Reported rates may be routinely underestimated due to
      limitations around assessment. Pre-stroke depression significantly increases odds
      of post-stroke depression.Protocol identifierPROSPERO identifier: CRD42017065544.

PMID- 30107867
TI  - Total Dietary Fiber (CODEX Definition) in Foods and Food Ingredients by a Rapid
      Enzymatic-Gravimetric Method and Liquid Chromatography: Collaborative Study,
      First Action 2017.16.
AB  - A method for measurement of total dietary fiber (TDF) has been validated. This
      method is applicable to plant materials, foods, and food ingredients as consumed,
      consistent with the 2009 CODEX definition (ALINORM 09/32/REP), and measures
      insoluble dietary fiber (IDF) and soluble dietary fiber (SDF), comprising SDF
      that precipitates in the presence of 78% ethanol (SDFP) and SDF that remains
      soluble in the presence of 78% ethanol (SDFS). The method is an update of AOAC
      Method 2009.01 and addresses each of the issues identified by analysts in using
      that method over the past 8 years. A total of 13 laboratories participated in the
      study, with all laboratories returning valid assay data for most of the 16 test
      portions (8 blind duplicates) consisting of samples with a range of content of
      traditional dietary fibers, resistant starch, and nondigestible oligosaccharides.
      The dietary fiber content of the eight test pairs ranged from 6.90 to 60.37 g/100
      g. TDF was calculated as the sum of IDF plus SDFP measured gravimetrically and
      SDFS measured by HPLC. The repeatability SD ranged from 0.27 to 0.76 g/100 g, and
      the reproducibility SD ranged from 0.54 to 3.99 g/100 g. The RSDr ranged from
      1.22 to 6.52%, and the RSDR ranged from 2.14 to 10.62%.

PMID- 30107865
TI  - Traumatic event exposure associated with increased food insecurity and eating
      disorder pathology.
AB  - OBJECTIVE: The primary aim was to investigate the association between food
      insecurity (FI) and eating disorders, which are nutrition-based public health
      problems, with traumatic event exposure in a low-income marginalized population.
      The study also investigated the association between traumatic event exposure,
      anxiety and weight stigma. DESIGN: The study used self-report surveys in a cross
      sectional design. SETTING: Food pantries affiliated with the local food bank in a
      major US city. SUBJECTS: Participants (n 503) consisted of clients presenting to
      food pantries. Participants were predominantly female (76.5 %), Latino/Hispanic
      (64.6 %) and low-income (59 % reported earning under $US 10 000 per year).
      RESULTS: Results indicated that 55.7 % of participants had directly experienced a
      traumatic event; this increased to 61.6 % when witnessing was included. Higher
      levels of FI were associated with greater traumatic event exposure. Increased
      exposure to traumatic events correlated with worsened overall eating disorder
      pathology (r=-0.239), weight stigma (r=-0.151) and anxiety (r=-0.210).
      CONCLUSIONS: The present study is the first to investigate the association of FI,
      eating disorders and trauma in a low-income marginalized population. Results
      indicate that exposure to traumatic events is common in this civilian population
      and that traumatic event exposure is associated with higher levels of FI and
      eating disorder pathology. Results indicate that further research is warranted
      given that traumatic event exposure, eating disorder pathology, weight stigma and
      anxiety may complicate effective delivery of public health interventions in those
      living with FI.

PMID- 30107866
TI  - Contaminated Shipping Materials Identified as the Source of Rotaviral Infection
      of Exported Mice.
AB  - Over a 4-wk period in 2017, we received notification from 7 different
      institutions that mice exported from our SPF barrier facilities had tested
      positive for mouse rotavirus (MRV). The exports originated from several different
      buildings across multiple campuses. Our institution excludes MRV in all of our
      barrier facilities and has historically been free of this virus. Extensive
      testing of our rooms from which the exported mice originated did not detect the
      presence of rotavirus. The single commonality among the 7 shipments was the use
      of shipping boxes acquired from one vendor. These shipping boxes arrived at our
      institution prepackaged with unsterilized feed and bedding, which we hypothesized
      was the source of the rotavirus. To test this hypothesis, we housed naive
      sentinel mice in clean cages with feed and bedding transferred from 29 unopened,
      unused shipping boxes. Sentinel mice were exposed to this bedding and feed for 14
      d and then evaluated through MRV serology and PCR assay. Of the 29 sentinels, 24
      were seropositive for MRV, and 14 of the 29 were PCR positive. These results
      provided direct evidence that MRV detected by recipient institutions originated
      from the contaminated feed or bedding within the shipping boxes. To our
      knowledge, this report is the first description of contaminated materials in
      shipping boxes resulting in rotaviral infection of mice during export.

PMID- 30107868
TI  - Subcutaneous C1-esterase inhibitor to prevent hereditary angioedema attacks:
      Safety findings from the COMPACT trial.
AB  - BACKGROUND: The first subcutaneous (SC) C1-esterase inhibitor concentrate (C1
      INH) was approved by the U.S. Food and Drug Administration in June 2017 as
      routine prophylaxis to prevent hereditary angioedema attacks in adolescents and
      adults at a dose of 60 IU/kg twice weekly based on the phase III Clinical Study
      for Optimal Management of Preventing Angioedema With Low-volume Subcutaneous C1
      Inhibitor Replacement Therapy (COMPACT) trial. OBJECTIVE: This article aimed to
      evaluate the relationship of the C1-INH (SC) dose regimens tested in the COMPACT
      trial (40 IU/kg and 60 IU/kg twice weekly) and the occurrence of adverse events
      (AEs). METHODS: Patients were instructed to record any AEs in their e-diary
      daily. Safety and tolerability were assessed based on reported AEs, including
      injection-site reactions (ISRs); unsolicited AEs (AEs other than ISRs); serious
      AEs; thrombotic, thromboembolic, anaphylactic, hypersensitivity, sepsis, and
      bacteremia events; inhibitory antibodies to C1-INH; and clinically significant
      abnormalities in laboratory assessments. Information on ISRs was specifically
      solicited. RESULTS: No relationship between the dose of C1-INH (SC) and the
      incidence of ISRs or unsolicited AEs was observed. The proportion of injections
      followed by at least one ISR was 12% with C1-INH (SC) 40 IU/kg versus 5% with 60
      IU/kg and 6% with placebo. No ISRs were serious or led to treatment
      discontinuation, and all resolved. There were no anaphylaxis, thromboembolic,
      sepsis, or bacteremia events reported during treatment with C1-INH (SC). All
      hypersensitivity AEs were nonserious, and the majority were assessed as being
      unrelated to treatment. No inhibitory antibodies to C1-INH were observed.
      CONCLUSION: C1-INH (SC) is safe and well tolerated with no dose-dependent safety
      concerns, as demonstrated in the COMPACT trial.Clinical trial NCT01912456, <ext
      link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri"
      xlink:href="http://www.clinicaltrials.gov">www.clinicaltrials.gov</ext-link>.

PMID- 30107869
TI  - Early start of the West Nile fever transmission season 2018 in Europe.
AB  - In Europe, surveillance indicates that the 2018 West Nile fever transmission
      season started earlier than in previous years and with a steeper increase of
      locally-acquired human infections. Between 2014 and 2017, European Union/European
      Economic Area (EU/EEA) and EU enlargement countries notified five to 25 cases in
      weeks 25 to 31 compared with 168 cases in 2018. Clinicians and public health
      authorities should be alerted to ensure timely implementation of prevention
      measures including blood safety measures.

PMID- 30107870
TI  - An early start of West Nile virus seasonal transmission: the added value of One
      Heath surveillance in detecting early circulation and triggering timely response
      in Italy, June to July 2018.
AB  - In Italy, the 2018 West Nile virus transmission season started early with a high
      number of cases reported. One-Health surveillance, within the Italian West Nile
      national preparedness and response plan, detected viral circulation 9 days before
      symptom-onset of the first confirmed human case; triggering timely implementation
      of blood and transplant safety measures. This is an example of how functional
      coordination allows health authorities to use early warning triggers from
      surveillance systems to implement preventive measures.

PMID- 30107871
TI  - Healthcare-associated pneumonia in acute care hospitals in European
      Union/European Economic Area countries: an analysis of data from a point
      prevalence survey, 2011 to 2012.
AB  - An aim of the ECDC point prevalence survey (PPS) in European Union/European
      Economic Area acute care hospitals was to acquire standardised healthcare
      associated infections (HAI) data. We analysed one of the most common HAIs in the
      ECDC PPS, healthcare-associated pneumonia (HAP). Standardised HAI case
      definitions were provided and countries were advised to recruit nationally
      representative subsets of hospitals. We calculated 95% confidence intervals (CIs)
      around prevalence estimates and adjusted for clustering at hospital level. Of
      231,459 patients in the survey, 2,902 (1.3%; 95% CI: 1.2-1.3) fulfilled the case
      definition for a HAP. HAPs were most frequent in intensive care units (8.1%; 95%
      CI: 7.4-8.9) and among patients intubated on the day of the survey (15%; 95% CI:
      14-17; n = 737 with HAP). The most frequently reported microorganism was
      Pseudomonas aeruginosa (17% of 1,403 isolates), followed by Staphylococcus aureus
      (12%) and Klebsiella spp. (12%). Antimicrobial resistance was common among
      isolated microorganisms. The most frequently prescribed antimicrobial group was
      penicillins, including combinations with beta-lactamase inhibitors. HAPs occur
      regularly among intubated and non-intubated patients, with marked differences
      between medical specialities. HAPs remain a priority for preventive
      interventions, including surveillance. Our data provide a reference for future
      prevalence of HAPs at various settings.

PMID- 30107873
TI  - Job vacancy at the European Centre for Disease Prevention and Control.

PMID- 30107872
TI  - Lack of serological evidence of Middle East respiratory syndrome coronavirus
      infection in virus exposed camel abattoir workers in Nigeria, 2016.
AB  - BackgroundMiddle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic
      threat of global public health concern and dromedary camels are the source of
      zoonotic infection. Although MERS-CoV is enzootic in dromedaries in Africa as
      well as the Middle East, zoonotic disease has not been reported in Africa.
      Methods: In an abattoir in Kano, Nigeria, we tested nasal swabs from camels and
      investigated 261 humans with repeated occupational exposure to camels, many of
      whom also reported drinking fresh camel milk (n = 138) or urine (n = 94) or using
      camel urine for medicinal purposes (n = 96). Results: Weekly MERS-CoV RNA
      detection in January-February 2016 ranged from 0-8.4% of camels sampled. None of
      the abattoir workers with exposure to camels had evidence of neutralising
      antibody to MERS-CoV. Conclusion: There is a need for more studies to investigate
      whether or not zoonotic transmission of MERS-CoV does take place in Africa.

PMID- 30107874
TI  - l-Thyroxine does not prevent immunemediated sensorineural hearing loss in
      autoimmune thyroid diseases.
AB  - OBJECTIVE: This is the first report dealing with immune-mediated inner ear
      disease (IMIED) hearing loss in a group of patients affected with autoimmune
      thyroid disease (AITD), whose treatment required corticosteroids, despite being
      treated with levothyroxine. Immunopathology linking the inner ear and the thyroid
      gland is also presented. PATIENTS: A total of 220 patients were selected with
      sensorineural hearing loss (SNHL) of causes other than presbycusis. Audiometry
      was performed and pure tone average was calculated before and after treatment
      with corticosteroids. RESULTS: Eighty-four (84) patients had SNHL of autoimmune
      origin, and 15 patients were diagnosed with AITD (Hashimoto's disease). Bilateral
      hearing loss was observed in 10 patients (66.5%). Sudden sensorineural hearing
      loss was the most frequent clinical form of presentation. Nine patients showed a
      hearing recovery greater than 10dB after corticosteroid treatment. CONCLUSIONS:
      Acquired hypothyroidism is thought to affect hearing due to different mechanisms.
      Although specific hormonal therapy may improve peripheral or central auditory
      disorders associated with hypothyroidism, the presence of IMIED in AITD patients
      requires another approach. Altered immune regulatory mechanisms involving Treg
      cells and CD4+CD45RO cells have been suggested in patients with AITD and IMIED.
      In the present study, although all the patients with hypothyroidism and
      subclinical hypothyroidism were being treated with levothyroxine, immune-mediated
      hearing loss was observed. Therapy with corticosteroids could achieve hearing
      recovery. Since inner ear and thyroid gland share possible antigen targets, we
      highlight the existence of IMIED in AITD patients and the importance of
      implementing appropriate therapy with corticosteroids.

PMID- 30107875
TI  - Algorithm for Treatment of Chronic Spontaneous Urticaria with Omalizumab.
AB  - BACKGROUND AND OBJECTIVE: Pivotal trials with omalizumab for treatment of chronic
      spontaneous urticaria (CSU) are generally run over 12 to 24weeks. However, in
      clinical practice, many patients need longer treatment. In this article, we
      present an algorithm for treatment with omalizumab. MATERIAL AND METHODS: The
      consensus document we present is the result of a series of meetings by the CSU
      working group of "Xarxa d'Urticaria Catalana i Balear" (XUrCB) at which data from
      the recent literature were presented, discussed, compared, and agreed upon.
      RESULTS: Treatment with omalizumab should be initiated at the authorized dose,
      and is adjusted at 3-monthly intervals according to the Urticaria Activity Score
      Over 7days, the Urticaria Control Test, or both. CONCLUSIONS: The algorithm
      proposed is designed to provide guidance on how to adjust omalizumab doses, how
      and when to discontinue the drug, and how to reintroduce it in cases of relapse.

PMID- 30107876
TI  - RNA on the move: The plasmodesmata perspective.
AB  - It is now widely accepted that plant RNAs can have effects at sites far away from
      their sites of synthesis. Cellular mRNA transcripts, endogenous small RNAs and
      defense-related small RNAs all move from cell to cell via plasmodesmata (PD), and
      may even move long distances in the phloem. Despite their small size, PD have
      complicated substructures, and the area of the pore available for RNA trafficking
      can be remarkably small. The intent of this review is to bring into focus the
      role of PD in cell-to-cell and long distance communication in plants. We consider
      how cellular RNAs could move through the cell to the PD and thence through PD.
      The protein composition of PD and the possible roles of PD proteins in RNA
      trafficking are also discussed. Recent evidence for RNA metabolism in organelles
      acting as a factor in controlling PD flux is also presented, highlighting new
      aspects of plant intra- and intercellular communication. It is clear that while
      the phenomenon of RNA mobility is common and essential, many questions remain,
      and these have been highlighted throughout this review.

PMID- 30107877
TI  - The metabolic roles of free amino acids during seed development.
AB  - Amino acids play vital roles in the central metabolism of seeds. They are
      primarily utilized for the synthesis of seed-storage proteins, but also serve as
      precursors for the biosynthesis of secondary metabolites and as a source of
      energy. Here, we aimed at describing the knowledge accumulated in recent years
      describing the changes occurring in the contents of free amino acids (FAAs)
      during seed development. Since several essential amino acids are found in low
      levels in seeds (e.g., Lys, Met, Thr, Val, Leu, Ile and His), or play unique
      functional roles in seed development (e.g., Pro and the non-proteinogenic gamma
      aminobutyrate [GABA]), we also briefly describe studies carried out in order to
      alter their levels in seeds and determine the effects of the manipulation on seed
      biology. The lion share of these studies highlights strong positive correlations
      between the biosynthetic pathways of FAAs, meaning that when the levels of a
      certain amino acid change in seeds, the contents of other FAAs tend to elevate as
      well. These observations infer a tight regulatory network operating in the
      biosynthesis of FAAs during seed development.

PMID- 30107878
TI  - The No-go decay system degrades plant mRNAs that contain a long A-stretch in the
      coding region.
AB  - RNA quality control systems identify and degrade aberrant mRNAs, thereby
      preventing the accumulation of faulty proteins. Non-stop decay (NSD) and No-go
      decay (NGD) are closely related RNA quality control systems that act during
      translation. NSD degrades mRNAs lacking a stop codon, while NGD recognizes and
      decays mRNAs that contain translation elongation inhibitory structures. NGD has
      been intensively studied in yeast and animals but it has not been described in
      plants yet. In yeast, NGD is induced if the elongating ribosome is stalled by a
      strong inhibitory structure. Then, the mRNA is cleaved by an unknown nuclease and
      the cleavage fragments are degraded. Here we show that NGD also operates in
      plant. We tested several potential NGD cis-elements and found that in plants,
      unlike in yeast, only long A-stretches induce NGD. These long A-stretches trigger
      endonucleolytic cleavage, and then the 5' fragments are degraded in a Pelota-,
      HBS1- and SKI2- dependent manner, while XRN4 eliminates the 3' fragment. We also
      show that plant NGD operates gradually, the longer the A-stretch, the more
      efficient the cleavage. Our data suggest that mechanistically NGD is conserved in
      eukaryotes, although the NGD inducing cis-elements could be different. Moreover,
      we found that Arabidopsis AtPelota1 functions in both NGD and NSD, while
      AtPelota2 represses these quality control systems. The function of plant NGD will
      be discussed.

PMID- 30107879
TI  - Brassica glucosinolate rhythmicity in response to light-dark entrainment cycles
      is cultivar-dependent.
AB  - Coordination of plant circadian rhythms with the external environment provides
      growth and reproductive advantages to plants as well as enhanced resistance to
      insects and pathogens. Since glucosinolates (GLSs) play a major role as plant
      defensive compounds and could affect the palatability and health value of edible
      crops, the aim of this study was to investigate the species-specific patterns in
      circadian rhythmicity of these plant phytochemicals. Five different GLS
      containing cultivars, from three Brassica crop species were studied. Plants were
      entrained to light-dark cycles (LD) for five weeks prior to release them into
      continuous light (LL). GLSs levels were monitored during five consecutive days
      (two days at LD conditions and three days at LL). The remaining plants were re
      entrained to LD cycles (Re-LD plants) and GLS levels were studied as stated
      before during two consecutive days. Results showed that the period and amplitude
      of GLSs circadian outputs were cultivar-dependent. In addition, we assessed that
      the plant endogenous clock can be re-entrained for GLSs accumulation after a
      period of free-running conditions. Together, these data suggests that Brassica
      cultivars keep track the time of the day to coordinate their defenses. The
      demonstration of the cultivar-specific circadian effect on the GLSs levels in
      plants of different Brassica cultivars have the potential to identify new targets
      for improving cultivar phytochemicals using temporally informed approaches. In
      addition, provides an exceptional model to study the complexity of signal
      integration in plants.

PMID- 30107880
TI  - Structural network of arabinogalactan proteins (AGPs) and pectins in apple fruit
      during ripening and senescence processes.
AB  - The cell wall is an essential framework determining the overall form of the plant
      cell. Our study was focused on the distribution of arabinogalactan proteins
      (AGPs), arabinan, and homogalacturonan in fruit cells during ripening and storage
      with emphasis on quantitative analysis of their presence in particular regions of
      the cell wall - plasma membrane. The localization of the examined compounds was
      determined with immunohistochemistry techniques and immunogold labelling. Spatio
      temporal colocalization between AGPs epitopes - [betaGlcA(1->3)-alphaGalA(1
      >2)Rha] recognized by JIM13 and MAC207 antibodies, and arabinan labelled by the
      LM16 antibody was detected in the inner cell wall layer, in association with the
      plasma membrane. The specific arrangement of AGP and arabinan epitopes
      differentiated them from homogalacturonan epitopes, consisting of GalA residues
      recognized by LM19 and LM20 antibodies in all the examined fruit maturity stages.
      The disruption of cell wall - plasma membrane continuum, observed during ripening
      associated softening process, was associated with both the substantial decrease
      of AGPs, pectins content and with remodeling of their arrangement. The results
      indicate that the textural properties of fruit during growth and postharvest
      storage, an attribute of fruit quality becoming selection criteria for consumers,
      depend on the existence of dynamic network organizing polysaccharides and
      glycoproteins in the extracellular matrix.

PMID- 30107881
TI  - Isolation and identification of wheat gene TaDIS1 encoding a RING finger domain
      protein, which negatively regulates drought stress tolerance in transgenic
      Arabidopsis.
AB  - Drought stress is a major factor that limits the yield and quality in wheat. In
      this study, we identified an orthologue of the rice gene OsDIS1 (Oryza sativa
      drought-induced SINA protein 1) in wheat (Triticum aestivum L.) called TaDIS1.
      TaDIS1 encodes a putative 301 amino acid protein with a C3HC4 RING finger
      conserved domain at the N-terminal and a SINA domain at the C-terminal. TaDIS1
      contains three exons and two introns. qRT-PCR analysis showed that TaDIS1
      expression was induced by PEG6000, NaCl, and abscisic acid (ABA) treatment. We
      generated TaDIS1-overexpressing transgenic Arabidopsis lines. Under drought
      stress conditions, the transgenic Arabidopsis plants had a lower germination
      rate, relative water content, and proline contents, with higher water loss,
      chlorophyll loss, relative electrical conductivity, and malondialdehyde contents
      compared with the wild type. The antioxidant enzyme (superoxide dismutase,
      peroxidase, and catalase) activity levels were lower in the transgenic plants.
      The TaDIS1-overexpressing plants had shorter roots with greater growth inhibition
      in response to mannitol treatment than the wild type, with increased
      hypersensitivity to ABA during seed germination and early seedling growth. The
      expression of stress-related genes in transgenic plants under drought stress
      suggests that TaDIS1 may function negatively in drought stress by regulating the
      stress response-related genes.

PMID- 30107882
TI  - Ectopic expression of FvWRKY42, a WRKY transcription factor from the diploid
      woodland strawberry (Fragaria vesca), enhances resistance to powdery mildew,
      improves osmotic stress resistance, and increases abscisic acid sensitivity in
      Arabidopsis.
AB  - WRKY transcription factors play a critical role in biotic and abiotic stress
      responses in plants, but very few WRKYs have been reported in strawberry plants.
      Here, a multiple stress-inducible gene, FvWRKY42, was isolated from the wild
      diploid woodland strawberry (accession Heilongjiang-3). FvWRKY42 expression was
      induced by treatment with powdery mildew, salt, drought, salicylic acid (SA),
      methyl jasmonate (MeJA), abscisic acid (ABA), and ethylene. The protein
      interaction network analysis showed that the FvWRKY42 protein interacts with
      various stress-related proteins. Overexpression of FvWRKY42 in Arabidopsis
      resulted in cell death, sporulation, slow hypha growth, and enhanced resistance
      to powdery mildew that was concomitant with increased expression of PR1 genes in
      Arabidopsis. Overexpression also led to enhanced salt and drought stress
      tolerance, increased primary root length and germination rate, decreased water
      loss rate, reduced relative electrolyte leakage, and malondialdehyde
      accumulation, and upregulation of superoxide dismutase and catalase activity.
      Additionally, FvWRKY42-overexpressing Arabidopsis plants showed increased ABA
      sensitivity during seed germination and seedling growth, increased stomatal
      closure after ABA and drought treatment, and altered expression of ABA-responsive
      genes. Collectively, our data demonstrate that FvWRKY42 may play an important
      role in powdery mildew infection and the regulation of salt and drought stress
      responses in plants.

PMID- 30107883
TI  - The fluorescent blue glow of banana fruits is not due to symplasmic plastidial
      catabolism but arises from insoluble phenols estherified to the cell wall.
AB  - Banana fruits are firstly green due to chlorophyll, then yellow due to
      carotenoids and finally turn black due to polyphenols. However, bananas glow blue
      when observed under UV light. It has been reported that chlorophylls fade to give
      rise to fluorescent chlorophyll catabolites (FCCs) in senescent banana leaves and
      in ripening banana peels. FCCs are short lived catabolic intermediates that
      ultimately lead to non-fluorescent chlorophyll catabolites (NCCs). FCCs are
      abundant in bananas due to hypermodification; therefore, it was concluded that
      FCC caused yellow bananas to glow blue. Experiments were performed in order to
      shed new light into the autofluorescence phenomenon. Microscopy performed on
      living plant samples contradict the interpretation that the fluorescent blue glow
      is mainly caused by FCC inside the cell. Blue fluorescence in banana emerges from
      the cell wall, not from the symplasm. It is not primarily caused by soluble
      chlorophyll catabolites in the vacuoles or senescing plastids. Insoluble
      phenolics from the apoplast make bananas shine strongly blue under black light.
      Chlorophyll is a light trap that generates black holes of blue fluorescence, and
      therefore cells with chloroplasts glow less blue. The white pulp of banana fruits
      shine more strongly than the outer peel. In both tissues autofluorescence arises
      from insoluble phenols that are estherified to the cell wall. In monocot species
      (banana, maize, sugarcanne), blue fluorescense was strongest in the cell wall,
      whereas in dicots (e.g. arabidopsis, spearmint, hibiscus), blue fluorescence may
      be dominant from cytosolic, vacuolar or plastidial compartments.

PMID- 30107884
TI  - In silico characterization and expression profiling of the diacylglycerol
      acyltransferase gene family (DGAT1, DGAT2, DGAT3 and WS/DGAT) from oil palm,
      Elaeis guineensis.
AB  - The diacylglycerol acyltransferases (DGAT) (diacylglycerol:acyl-CoA
      acyltransferase, EC 2.3.1.20) are a key group of enzymes that catalyse the final
      and usually the most important rate-limiting step of triacylglycerol biosynthesis
      in plants and other organisms. Genes encoding four distinct functional families
      of DGAT enzymes have been characterised in the genome of the African oil palm,
      Elaeis guineensis. The contrasting features of the various isoforms within the
      four families of DGAT genes, namely DGAT1, DGAT2, DGAT3 and WS/DGAT are presented
      both in the oil palm itself and, for comparative purposes, in 12 other oil crop
      or model/related plants, namely Arabidopsis thaliana, Brachypodium distachyon,
      Brassica napus, Elaeis oleifera, Glycine max, Gossypium hirsutum, Helianthus
      annuus, Musa acuminata, Oryza sativa, Phoenix dactylifera, Sorghum bicolor, and
      Zea mays. The oil palm genome contains respectively three, two, two and two
      distinctly expressed functional copies of the DGAT1, DGAT2, DGAT3 and WS/DGAT
      genes. Phylogenetic analyses of the four DGAT families showed that the E.
      guineensis genes tend to cluster with sequences from P. dactylifera and M.
      acuminata rather than with other members of the Commelinid monocots group, such
      as the Poales which include the major cereal crops such as rice and maize.
      Comparison of the predicted DGAT protein sequences with other animal and plant
      DGATs was consistent with the E. guineensis DGAT1 being ER located with its
      active site facing the lumen while DGAT2, although also ER located, had a
      predicted cytosol-facing active site. In contrast, DGAT3 and some (but not all)
      WS/DGAT in E. guineensis are predicted to be soluble, cytosolic enzymes.
      Evaluation of E. guineensis DGAT gene expression in different tissues and
      developmental stages suggests that the four DGAT groups have distinctive
      physiological roles and are particularly prominent in developmental processes
      relating to reproduction, such as flowering, and in fruit/seed formation
      especially in the mesocarp and endosperm tissues.

PMID- 30107885
TI  - Risk assessment for liver resection.
AB  - BACKGROUND: In recent years, the profile for patients undergoing complex liver
      resections has changed, with mortality rates remaining generally stable. With
      these factors in mind, the objective of this study was to evaluate the variables
      associated with surgical outcomes after hepatectomy and identify groups at high
      risk for postoperative mortality. METHODS: The records of 1,796 patients who
      underwent liver resection of more than one liver segment at the Department of
      General and Transplantation Surgery, University Hospital Heidelberg, Germany,
      were analyzed. The primary end point was a 90-day in-hospital mortality. Logistic
      regression analyses were performed to identify risk factors associated with
      mortality. A risk score was created in accordance with weighted points based on
      the odds ratios obtained from multivariate logistic regression analyses. External
      validation of the score was performed, using data derived from 281 patients at
      the board-certified center for liver surgery in Karlsruhe, Germany. RESULTS: The
      overall patient morbidity rate (Clavien-Dindo Grade II or greater) was 32%. The
      30- and 90-day mortality rates were 3.0% and 4.5%, respectively. In multivariate
      analysis, factors independently associated with risk for 90-day in-hospital
      mortality were age >=60 years (OR 3.71), ASA classification III (OR 2.94), ASA IV
      (15.66), perihilar cholangiocarcinoma (OR 5.65), intrahepatic cholangiocarcinoma
      (OR 3.08), INR >= 1.1 (OR 2.43), g-GT >= 60 U/L (OR 2.86), platelet count <=
      120/nL (OR 5.52), creatinine >= 2 mg/dL (OR 9.85), and right trisectionectomy (OR
      2.88). The 90-day mortality-risk score that was created based on these factors
      effectively stratified patients into very low risk (0-1 points, 0.2% mortality
      rate in 662 patients), low risk (2-3 points, 2.9% mortality rate in 769
      patients), medium risk (4-5 points, 14.7% mortality rate in 232 patients), and
      high risk (>=6 points, 33% mortality rate in 57 patients) groups (P < .0001). As
      a performance metric, the C-index for the proposed risk score for 90-day
      mortality was 0.86; whereas external validation revealed that this C-index was
      0.89 (P = .0002). CONCLUSION: Based on patient-related factors and procedure
      specific variables, the proposed preoperative-risk score can be used to identify
      high-risk patients to determine 90-day mortality after liver resection.

PMID- 30107886
TI  - Predicting non-home discharge in epithelial ovarian cancer patients: External
      validation of a predictive model.
AB  - OBJECTIVE: To externally validate a model predicting non-home discharge in women
      undergoing primary cytoreductive surgery (CRS) for epithelial ovarian cancer
      (EOC). METHODS: Women undergoing primary CRS via laparotomy for EOC at three
      tertiary medical centers in an academic health system from January 2010 to
      December 2015 were included. Patients were excluded if they received neoadjuvant
      chemotherapy, had a non-epithelial malignancy, were not undergoing primary
      cytoreduction, or lacked documented model components. Non-home discharge included
      skilled nursing facility, acute rehabilitation facility, hospice, or inpatient
      death. The predicted probability of non-home discharge was calculated using age,
      pre-operative CA-125, American Society of Anesthesiologists (ASA) score and
      Eastern Cooperative Oncology Group (ECOG) performance status as described in the
      previously published predictive model. Model discrimination was calculated using
      a concordance index and calibration curves were plotted to characterize model
      performance across the cohort. RESULTS: A total of 204 admissions met inclusion
      criteria. The overall rate of non-home discharge was 12% (95% CI 8-18%). Mean age
      was 60.8 years (SD 11.0). Median length of stay (LOS) was significantly longer
      for patients with non-home discharge (8 vs. 5 days, P < 0.001). The predictive
      model had a concordance index of 0.86 (95% CI 0.76-0.93), which was similar to
      model performance in the original study (CI 0.88). The model provided accurate
      predictions across all probabilities (0 to 100%). CONCLUSIONS: Non-home discharge
      can be accurately predicted using preoperative clinical variables. Use of this
      validated non-home discharge predictive model may facilitate preoperative patient
      counseling, early discharge planning, and potentially decrease cost of care.

PMID- 30107887
TI  - Fish associated with a subsea pipeline and adjacent seafloor of the North West
      Shelf of Western Australia.
AB  - Information on the potential ecological value of offshore oil and gas
      infrastructure is required as it reaches the end of its operational life and
      decisions must be made regarding the best practice option for decommissioning.
      This study uses baited remote underwater stereo-video systems to assess fish
      assemblages along an offshore subsea pipeline and in adjacent natural seabed
      habitats at ~140 m depth on the North West Shelf of Western Australia. A total of
      955 fish from 40 species and 25 families were recorded. Species richness was, on
      average 25% higher on the pipeline (6.48 +/- 0.37 SE) than off (4.81 +/- 0.28 SE)
      while relative abundance of fish was nearly double on the pipeline (20.38 +/-
      2.81 SE) than in adjacent natural habitats (10.97 +/- 1.02 SE). The pipeline was
      characterised by large, commercially important species known to associate with
      complex epibenthic habitat and, as such, possessed a biomass of commercial fish
      ca 7.5 * higher and catch value ca. 8.6 * ($65.11 +/- $11.14 SE) than in adjacent
      natural habitats ($7.57 +/- $2.41 SE). This study has added to the knowledge of
      fish assemblage associations with subsea infrastructure and provides a greater
      understanding of the ecological and fisheries implications of decommissioning,
      helping to better inform decision-making on the fate of infrastructure.

PMID- 30107888
TI  - Comprehensive approach to restoring urban recreational reservoirs. Part 2 - Use
      of zooplankton as indicators for the ecological quality assessment.
AB  - The presented research is part of the LIFE project ("EH-REK" LIFE08
      ENV/PL/000517) on innovative restoration methods for small urban impoundments in
      the city of Lodz (Poland). The objective was to evaluate the usefulness of
      zooplankton as a biological quality element, when assessing the effectiveness of
      restoration efforts in three urban reservoirs and a one pond. The fifth
      unrestored pond was used as an example of the progressive eutrophication of an
      urban ecosystem. Studies were conducted during two periods: before (2010-2012)
      and after (2013-2016) restoration. A selection of zooplankton indices, including
      the rotifer trophic state index (TSIROT), was used. The influence of the
      supplying river resulted in the negligible responses of biological parameters to
      the restoration efforts in the Upper Arturowek (UA) reservoir, which is the first
      in cascade of reservoirs. However, clear symptoms of water quality improvements
      were observed in the other two reservoirs (the Middle Arturowek, MA; the Lower
      Arturowek, LA) and in the Bzura-17 (B17) pond. After restoration, the
      contribution of species indicative of high trophic levels decreased in these
      ecosystems. The TSIROT was strongly positively correlated with the trophic state
      index based on chlorophyll a, and both parameters significantly decreased in the
      MA, LA and B17. In the unrestored pond (B11), the successive increase in the
      concentrations of chemical parameters indicated progressing eutrophication.
      Interestingly, since 2013, the TSIROT values clearly decreased in B11, but the
      strong negative correlation between ammonium concentration and rotifer density
      indicated that the reduced TSIROT values didn't result from improvements in water
      quality; rather, they resulted from the increases in pollution and the associated
      harmful impacts on Rotifera. In conclusion, the TSIROT can be a useful tool for
      assessing the ecological quality of small urban ecosystems; however, the use of
      biological indices must be supported by also monitoring physicochemical
      parameters.

PMID- 30107889
TI  - What are the required components of pre- and post-test counseling?
AB  - Prenatal care providers are faced with a myriad of decisions about how to offer
      genetic screening and testing in ways that are appropriate to their patient
      population and their workflow. Among the critical issues brought to the forefront
      of rapidly advancing genetic and genomic technologies is the importance of pre-
      and post-test counseling. This document is a synthesis of proceedings of a
      workshop sponsored by the American College of Obstetricians and Gynecologists,
      the American College of Medical Genetics and Genomics, and the Society for
      Maternal-Fetal Medicine, on January 24-25, 2017, during which invited experts
      discussed required components of pre- and post-test counseling and associated
      concerns in the provision of prenatal care.

PMID- 30107890
TI  - The effects of bisphenol A on some plasma cytokine levels and distribution of
      CD8+ and CD4+ T lymphocytes in spleen, ileal Peyer's patch and bronchus
      associated lymphoid tissue in rats.
AB  - The effects of bisphenol A on the some plasma cytokine levels and distribution of
      CD8+ and CD4+ T lymphocytes in spleen, ilealPeyer's patch and bronchus-associated
      lymphoid tissue in rats were investigated. A total of fourty male Wistar Albino
      rats were divided into five groups including 8 rats in each one: control,
      vehicle, BPA 5, BPA 50 and BPA 500 groups. Doses of 5, 50 and 500 MUg/kg BPA were
      dissolved in ethanol, then mixed with corn oil. The control group received no
      treatment. The vehicle group was given the ethanol-corn oil mixture. BPA 5, BPA
      50 and BPA 500 groups were given, respectively, 5, 50, and 500 MUg/kg/day orally.
      In blood samples, IL-4, IL-6, IL-10 and TNF-alpha plasma levels were determined
      with ELISA. Tissue samples (spleen, ileal Peyer's patches and lung) were
      processed by means of routine histological techniques. CD4 and CD8 were stained
      immunohistochemically. Data obtained from this study showed that, BPA causes the
      alteration on immune parameters including cytokine profile, distribution of CD8+
      and CD4+ T lymhpocytes in spleen and ileal Peyer's patches. Present study
      indicated that BPA may affect immune systems even at lower doses.Disruption of
      immun system cells and cytokine levels can result in harmful outcomes triggering
      autoimmune diseases and immunodeficiencies.

PMID- 30107891
TI  - Sex differences in symptoms experienced, knowledge about symptoms, symptom
      attribution, and perceived urgency for treatment seeking among acute coronary
      syndrome patients in Karachi Pakistan.
AB  - BACKGROUND: Patients' experience of acute coronary syndrome (ACS) symptoms is
      important in determining their prehospital delay. OBJECTIVE: To explore gender
      differences in acute symptoms of ACS, knowledge about the symptoms, their
      attribution, and perception of urgency, among Pakistani ACS patients. METHODS:
      Comparative, cross-sectional study design with 249 ACS patients. RESULTS: The
      most commonly reported symptoms were ghabrahat (fidgetiness), chest pain, and
      chest heaviness. Most atypical symptoms were experienced more by women, such as
      nausea/vomiting (p < 0.001), backache (p < 0.001), palpitations (p = 0.004), and
      epigastric pain (p = 0.005). Chest pain and palpitations were the symptoms most
      commonly attributed to cardiac causes, whereas epigastric pain was most commonly
      attributed to non-cardiac causes by both men and women. Significantly more women
      than men perceived dyspnea (p = 0.026), nausea/vomiting (p = 0.027), sweating (p
      = 0.014), and palpitations (p = 0.01) as symptoms not at all urgent for
      treatment. CONCLUSIONS: Gender disparity in symptom experience along with the
      women's perception of non-urgency for their symptoms, could lead to delayed care
      seeking.

PMID- 30107892
TI  - [Melatonin: Physiological and pharmacological aspects related to sleep: The
      interest of a prolonged-release formulation (Circadin(r)) in insomnia].
AB  - Melatonin is a hormone secreted by the pineal gland. It displays a very marked
      nycthohemeral rhythm, which is entrained to the light dark cycle. The secretion
      spreads over 8-10 hours, with a maximum around 3-4 a.m. Melatonin plays the role
      of an endogenous synchronizer which regulates circadian rhythms, especially the
      sleep/wake and temperature rhythms. Acute melatonin administration reduces sleep
      latency, increases theta/alpha power and spindle activity (soporific activity).
      Fast-release melatonin preparations showed inconstant effects in insomnia.
      Melatonin displays a short blood half-life, a fast turn over and undergoes a high
      first-pass hepatic metabolism. More than 80% is excreted exclusively in the urine
      as 6-sulfatoxymelatonin. The individual's capacity to produce the endogenous
      hormone, the decline in circadian clock output and the increase in complaints of
      poor sleep quality at older age led to develop a prolonged-release melatonin
      preparation to mimic the endogenous secretion in patients. This reviews provides
      data on physiological and pharmacological melatonin effects related to sleep and
      summarizes trials published about Circadin(r) efficacy and tolerance in insomnia.
      Preliminary therapeutic data on other indications are given. The main clinically
      relevant benefits are improvements in sleep quality and latency, next-day morning
      alertness and quality of life. The response develops over several days. An oral 2
      mg dose once daily, for 3 months, is generally well tolerated with no rebound,
      withdrawal or 'hangover' effects and no safety concerns on concomitant therapy
      with antihypertensive, antidiabetic, lipid-lowering or anti-inflammatory drugs.
      Untoward effects of hypnotics on cognition, memory, postural stability and sleep
      structure are not seen with Circadin(r). Given as a first-line prescription, with
      13 weeks' posology and the lack of rebound effects, Circadin(r) has the potential
      to improve quality of life in insomnia patients aged 55 years and older and avoid
      long-term use of hypnotics.

PMID- 30107893
TI  - Immunoglobulin G glycosylation in aging and diseases.
AB  - The Immunoglobulin G (IgG) glycome is well known for its heterogeneity and shows
      a significant degree of variation within populations. IgG glycome composition is
      influenced both by genes and by environment, making it an excellent biomarker of
      a person's general health state, i.e. biological age. IgG glycosylation appears
      to be highly regulated, both during homeostasis and in cases of its disturbance.
      Changes in IgG glycosylation patterns have been observed in aging and in various
      diseases. Differential IgG glycosylation is known to modulate IgG effector
      functions and is involved in disease development and progression, representing
      both a predisposition and a functional mechanism involved in disease pathology.
      This makes IgG glycosylation analysis a promising add-on to improve existing
      disease biomarkers.

PMID- 30107894
TI  - Clinical ultrasonography and abdominal aortic aneurysms in Internal Medicine.

PMID- 30107895
TI  - Liver metastasis from adenoid cystic carcinoma: imaging and histologic features.
AB  - Adenoid cystic carcinoma is a rare tumour. The reported incidence of isolated
      metastases to the liver is rare but possible and it seems to be more likely in
      case of perineural invasion.

PMID- 30107896
TI  - Treatment outcomes and incidence of brain metastases in pulmonary large cell
      neuroendocrine carcinoma.
AB  - INTRODUCTION: Large cell neuroendocrine carcinoma (LCNEC) is a rare type of high
      grade pulmonary neuroendocrine tumor. The study objective is to investigate its
      survival outcomes, incidence of brain metastases, and patterns of recurrence.
      METHODS: This is a single center study of patients with pathologic diagnosis of
      pulmonary LCNEC. Patient data were collected retrospectively and analyzed,
      including survival, incidence of brain metastases, and patterns of recurrence.
      RESULTS: Of 87 patients (stages I: 24, II: 14, III: 23, IV: 26), 52 were managed
      curatively and 35 palliatively. The median follow-up time was 17.3 months (range
      0.6-89.5) for those treated with curative intent and 7.0 months (range 0.1-28.6)
      for those treated palliatively. The 2- and 5-year overall survival (OS) rates are
      48.4% and 25.5% for the curative group, with a median OS of 13.5 months. In the
      palliative group, the OS are 30.8% at 1 year and 6.8% at 2 years, with a median
      OS of 7.0 months. Thirty-eight of 52 (73%) patients treated with curative intent
      had disease relapse, with the common sites being regional lymph nodes (20), brain
      (18), bones (11), and liver (9). The incidence of brain recurrence among those
      managed curatively are 21.4% and 41.3%, respectively at 1 and 2 years. Of 18
      patients experiencing brain metastases, 14 developed them as part of a first
      relapse. CONCLUSIONS: LCNEC's survival outcomes are poor. The incidence of brain
      metastases is higher than what is observed for other types of nonsmall cell lung
      cancers. Prophylactic cranial irradiation should be investigated as a means of
      improving outcomes.

PMID- 30107897
TI  - Involved-field irradiation for elderly bladder cancer patients.
AB  - OBJECTIVES: Considering that adjuvant radiation therapy is one of the most common
      treatment methods and the influence of the clinical target volume to treatment
      related toxicity, this study aimed to observe the differences in treatment
      failures about involved-field irradiation (IFI) without lymph node areas versus
      elective nodal irradiation (ENI) with lymph node areas in elderly patients with
      bladder cancer. MATERIAL AND METHODS: Ninety-two elderly bladder cancer patients
      were analyzed from January 2010 to December 2014 in one institution. The primary
      inclusion criteria were previous after transurethral resection of bladder tumor
      or partial cystectomy with adjuvant radiotherapy, and the radiation techniques
      included IFI or ENI. The study required that elderly patients did not received
      radiotherapy before treatment. We observed treatment-related toxicity and tumor
      failures, evaluated local progression-free survival, estimated the 3-year overall
      survival, and analyzed prognostic factors, after IFI and ENI in elderly bladder
      cancer patients. The outcomes were determined by chi square tests, Kaplan-Meier
      method and Cox multiple factors analysis. RESULTS: In the experimental group, 42
      patients (45.65%) received IFI, and a matched group of 50 patients (54.35%)
      received ENI. With a median follow-up of 31.47 months (range 4.00-86.00 months),
      the Kaplan-Meier analysis with a log-rank test demonstrated a statistical
      difference between the IFI group and the ENI group in acute toxicity (45.23% vs
      72.00%, P = 0.008). However, there were no statistical differences in the 3-year
      overall survival rate (45.20% vs 48.00%, P = 0.860) or the duration of local
      progression-free survival (24.98 vs 34.30, P =0.729). CONCLUSIONS: IFI is
      feasible in elderly bladder cancer patients, as shown by a decrease in acute
      toxicity and no increase in local failure. We need a large number of clinical
      trials and data to further confirm these results.

PMID- 30107898
TI  - Foreword.

PMID- 30107899
TI  - 48-Year-Old Woman With Bilateral Lower Extremity Paresthesias and Weakness.

PMID- 30107900
TI  - Fibroblast-seeded collagen gels in response to dynamic equibiaxial mechanical
      stimuli: A biomechanical study.
AB  - The remodeling of fibroblast-seeded collagen gels in response to dynamic
      mechanical stimuli was investigated by using a newly developed biaxial culture
      system capable of cyclically stretching planar soft tissues. Fibroblast-seeded
      collagen gels were subjected to three distinct dynamic mechanical conditions for
      six days: Cyclic Equibiaxial Stretching at two constant strain magnitudes (CES-7%
      and CES-20%), and Cyclic Equibiaxial Stretching with incrementally Increasing
      stain magnitude (ICES, 7% -> 15% -> 20% each for two days). The frequency of
      cyclic stretching was set at 1 Hz. At the end of culture, mechanical properties
      of the gels were examined by biaxial mechanical testing and checked again upon
      the removal of seeded cells. Collagen microstructure within the gels was
      illustrated by multiphoton microscopy. The mRNA levels of collagen type I and
      type III and fibronectin in the cells were examined by reverse transcription PCR.
      The protein expression of alpha-smooth muscle actin was detected by
      immunohistochemistry. We found that the gels cultured under cyclic stretching
      were stiffer than those cultured under static stretching. Particularly, the
      stiffness appeared to be significantly enhanced when the ICES was employed. The
      enhancement of mechanical properties by cyclic stretching appeared to persist
      upon cell removal, suggesting an irreversible remodeling of extracellular matrix.
      Second harmonic generation images showed that collagen fibers became thicker and
      more compact in the gels cultured under cyclic stretching, which may explain the
      mechanical findings. The mRNA expression of collagen type I in the cells of the
      ICES was significantly greater than that of the other groups except for the CES
      20%. This study suggests that when cyclic stretching is to be used in engineering
      soft tissues, incrementally increasing strain magnitude may prove useful in the
      development of the tissue.

PMID- 30107901
TI  - A Simplified Formula Discriminating Subtle Anterior Wall Myocardial Infarction
      from Normal Variant ST-Segment Elevation.
AB  - Benign variant (BV) ST-segment elevation (STE) is present in anterior chest leads
      in most individuals and may cause diagnostic confusion in patients presenting
      with chest pain. Recently, 2 regression formulas were proposed for
      differentiation of BV-STE from anterior ST-elevation myocardial infarction (MI)
      on the electrocardiogram, computation of which is heavily device-dependent. We
      hypothesized that a simpler visual-assessment-based formula, namely (R-wave
      amplitude in lead V4 + QRS amplitude in V2) - (QT interval in millimeters + STE60
      in V3), will be noninferior to these formulas. Consecutive cases of proven left
      anterior descending occlusion were reviewed, and those with obvious ST elevation
      MI were excluded. First 200 consecutive patients with noncardiac chest pain and
      BV-STE were also enrolled as a control group. Relevant electrocardiographic
      parameters were measured. There were 138 anterior MI and 196 BV-STE cases. Our
      simple formula was superior to the 3- and noninferior to the 4-variable formulas.
      This new practical formula had an excellent area-under curve of 0.963 (95%
      confidence interval, 0.946 to 0.980, p<0.001). It also had a sensitivity,
      specificity and diagnostic accuracy of 86.9%, 92.3%, and 90.1%, respectively. In
      conclusion, a simple visual assessment-based formula can reliably differentiate
      STE MI from BV-STE. Also, our results emphasize that focusing only on STE for
      diagnosing acute coronary occlusion is extremely insensitive and even puts the
      term "STEMI" itself into question.

PMID- 30107902
TI  - Clinical Spectrum and Management Implications of Left Ventricular Outflow
      Obstruction With Mild Ventricular Septal Thickness in Hypertrophic
      Cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HC) has historically been characterized as a disease
      of substantial left ventricular hypertrophy, often associated with dynamic left
      ventricular outflow tract obstruction. However, we have recently encountered
      patients with subaortic obstruction and only minimal basal septal thickness,
      raising important management implications. Thereby, we sought to characterize the
      natural history and treatment strategies for this under-recognized subgroup of HC
      patients with dynamic obstruction. Of 1,591 consecutive patients with a HC
      diagnosis, 113 (7%) were identified with outflow obstruction due to elongated
      mitral valve leaflets producing systolic anterior motion and septal contact
      typical of HC (gradient, 84 +/- 29 mm Hg at rest or with exercise), with maximal
      ventricular septal thickness <=15 mm, including 14 patients with only 10 to 12
      mm. In addition to the mechanism of outflow obstruction, other evidence
      supporting a HC diagnosis prominently included: positive HC family history and/or
      pathogenic sarcomere mutation, arrhythmic sudden death event, typical
      histopathology of septal muscle, and characteristic mitral valve and papillary
      muscle anomalies. Over 3.8 +/- 3.5 years, 41 patients (36%) developed severe
      heart failure including 36 who have undergone myectomy associated with
      reconstruction of the outflow tract and mitral valve apparatus, resulting in
      relief of gradient without iatrogenic ventricular septal defect or mitral valve
      replacement. Postoperatively, all 36 patients have survived with symptom relief
      to New York Heart Association classes I/II. In conclusion, these observations
      expand the HC clinical profile and phenotype to include an under-appreciated
      subgroup in which disease expression includes outflow obstruction due primarily
      to an elongated mitral valve, associated with only minimal (or normal)
      ventricular septal thickness. Such HC patients can develop marked functional
      limitation amenable to an operative strategy that effectively relieved symptoms
      due to outflow obstruction, but without mitral valve replacement.

PMID- 30107903
TI  - Barriers to Healthcare Access and to Improvements in Health-Related Quality of
      Life After an Acute Coronary Syndrome (From TRACE-CORE).
AB  - Little is known about how barriers to healthcare access affect health-related
      quality of life (HRQOL) after an acute coronary syndrome (ACS). In a large cohort
      of ACS survivors from 6 medical centers in Massachusetts and Georgia enrolled
      from 2011 to 2013, patients were classified as having any financial barriers, no
      usual source of care (USOC), or transportation barriers to healthcare based on
      their questionnaire survey responses. The principal study outcomes included
      clinically meaningful declines in generic physical and mental HRQOL and in
      disease-specific HRQOL from 1 to 6 months posthospital discharge. Adjusted
      relative risks (aRRs) for declines in HRQOL were calculated using Poisson
      regression models, controlling for several sociodemographic and clinical factors
      of prognostic importance. In 1,053 ACS survivors, 29.0% had a financial barrier,
      14.2% had no USOC, and 8.7% had a transportation barrier. Patients with a
      financial barrier had greater risks of experiencing a decline in generic physical
      (aRR 1.48, 95% confidence interval [CI] 1.17, 1.86) and mental (aRR 1.36, 95% CI
      1.07, 1.75) HRQOL at 6 months. Patients with 2 or more access barriers had
      greater risks of decline in generic physical (aRR 1.53, 95% CI 1.20, 1.93) and
      mental (aRR 1.50, 95% CI 1.17, 1.93) HRQOL compared with those without any
      healthcare barriers. There was a modest association between lacking a USOC and
      experiencing a decline in disease-specific HRQOL (aRR 1.46, 95% CI 0.96, 2.22).
      Financial and other barriers to healthcare access may be associated with
      clinically meaningful declines in HRQOL after hospital discharge for an ACS.

PMID- 30107904
TI  - Relation of Alcohol Consumption to Risk of Heart Failure in Patients Aged 65 to
      84 Years With Hypertension.
AB  - Although a high level of alcohol consumption is associated with cardiomyopathy,
      the benefit or risk of moderate alcohol consumption on incident heart failure
      (HF) is unknown. This study examined the association between alcohol consumption
      and risk for HF in older adults with hypertension. The study analyzed data from a
      cohort of 6,083 participants aged 65 to 84 years at baseline (1995 to 2001)
      followed for a median of 10.8 years during and after the Second Australian
      National Blood Pressure Study. Frequency and amount of alcohol consumption were
      self-reported at baseline and during the clinical trial. The percentages of
      current drinkers, former drinkers, and never-drinkers at baseline were 4,400
      (72%), 394 (6%), and 1,289 (21%), respectively. Incident HF was diagnosed in 183
      men and 136 women. After adjustment for multiple confounders, alcohol consumption
      was not significantly associated with HF. Compared with never-drinkers, the
      adjusted hazard ratios (95% confidence interval) for those who consume 1 to 7, 8
      to 14, and >14 drinks/week at baseline were 0.87 (0.59 to 1.30), 0.96 (0.57 to
      1.60), and 0.71 (0.25 to 2.02), respectively in women, and 0.81 (0.47 to 1.38),
      0.77 (0.43 to 1.38), and 1.04 (0.59 to 1.84), respectively in men. The findings
      of lack of an association between alcohol consumption and risk of HF persisted in
      the analyses comparing the risk of HF across each level of drinking at baseline
      or at follow-up with never-drinkers. In the present study, there was no evidence
      for benefit or risk of alcohol consumption, reported at baseline or at follow-up,
      in relation to incident HF in both men and women.

PMID- 30107905
TI  - Heart Rate as a Predictor of Outcome Following Percutaneous Coronary
      Intervention.
AB  - Data from previous studies of patients with heart failure and coronary artery
      disease suggest that those with higher resting heart rates (HRs) have worse
      cardiovascular outcomes. We sought to evaluate whether HR immediately before
      percutaneous coronary intervention (PCI) is an independent predictor for 30-day
      outcome. We analyzed the outcome of 3,720 patients who had HR recorded before PCI
      from the Melbourne Interventional Group registry. HR and outcomes were analyzed
      by quintiles, and secondarily by dichotomizing into <70 or >=70 beats/min.
      Patients with cardiogenic shock, intra-aortic balloon pump or inotropic support,
      and out-of-hospital arrest were excluded. The mean +/- SD HR was 70.9 +/- 14.7
      beats/min. HR by quintile was 55 +/- 5, 64 +/- 2, 70 +/- 1, 77 +/- 3, and 93 +/-
      13 beats/min, respectively. Patients with higher HR were more likely to be women,
      current smokers, have higher systolic and diastolic blood pressure, atrial
      fibrillation, recent heart failure, lower ejection fraction, and ST-elevation
      myocardial infarction as the indication for the PCI (all p <=0.002). However,
      rates of treated hypertension, multivessel disease, previous myocardial
      infarction, PCI, and coronary bypass surgery were lower (all p <=0.004).
      Increased HR was associated with higher 30-day mortality (p for trend = 0.04),
      target vessel revascularization (p for trend = 0.003), and 30-day major adverse
      cardiac events (MACE) (p for trend = 0.004). In a multivariable analysis, HR was
      an independent predictor of 30-day MACE (OR 1.21 per quintile; 95% confidence
      interval (CI): 1.06 to 1.39, p = 0.004). When dichotomized into <70 or >=70
      beats/min, HR independently predicted both 30-day MACE (OR 1.59, 95% CI 1.08 to
      2.36, p = 0.02) and 30-day mortality (OR 2.80, 95% CI 1.10 to 7.08, p = 0.03). In
      conclusion, HR immediately before PCI is an independent predictor of adverse 30
      day cardiovascular outcomes.

PMID- 30107906
TI  - Evolution of Length of Stay After Surgical and Transcatheter Aortic Valve
      Implantation Over 8 Years in 1,849 Patients >75 Years of Age and Comparison
      Between Transfemoral and Transsubclavian Transcatheter Aortic Valve Implantation.
AB  - Minimized length of hospitalization (LoS) and lower risk of hospitalization
      related complications are key requirements in the treatment of aortic valve
      disease, mainly in the elderly candidates. Our objective was to evaluate
      evolution of LoS after surgical (SAVR) or transcatheter aortic valve implantation
      (TAVI) and its predictors. We enrolled 1,849 elderly (aged >75) patients
      receiving SAVR or TAVI from 2009 to 2016. In the surgical cohort (n = 1,006) the
      mean LoS slightly decreased from 13.81 +/- 9.27 days (2009) to 10.96 +/- 3.77
      (2016); in the TAVI cohort (n = 843), LoS passed from 13.33 +/- 9.17 (2009) to
      6.21 +/- 4.30 days (2016). All-cause mortality at 1 month was 3.77 % (SAVR)
      versus 4.7% (TAVI) (p >0.05). Among Transfemoral TAVI (TF, n = 681), and
      Transsubclavian TAVI (TS, n = 62), average LoS was comparable (7.38 days +/- 7.11
      vs 7.31 +/- 4.32; median 6.0 and 6.0 days, p = 0.07). Procedural success was
      reached in 93% (TF) and in 85.4% (TS) (p = 0.20). There were no meaningful
      differences among TF and TS in terms of VARC-2 postprocedural morbidity, except
      for the rate of vascular access-related complications; these occurred in 8.8% of
      cases in the TF group versus 1.6% in the TS group (p = 0.05). In conclusion the
      present analysis showed a faster improvement in terms of LoS for TAVI compared
      with SAVR over 8 years of activity. The 2 strategies presented comparable all
      causes mortality at 30 days. LoS, rates of procedural success and complications
      were comparable among TF and TS TAVI; nonetheless, vascular access-related
      complications were more frequent in the TF cohort. This suggests the validity of
      the TS route as an alternative to the TF approach.

PMID- 30107907
TI  - Varying Effects of Body Mass Index and Mortality in Different Risk Groups.
AB  - It is unclear why high body mass index (BMI) is associated with a lower risk of
      death in patients with cardiovascular disease (CVD). We hypothesized that the
      impact of higher BMI varies by the patient's baseline risk of death. We analyzed
      data from 14 prospective studies conducted by us in 50 countries of 170,470
      patients: 22.8% without CVD, 29.4% with stable CVD and 47.8% with acute coronary
      syndromes (ACS). Compared with overweight (BMI 25 to 29.9 kg/m2), normal weight
      (BMI 20 to 24.9 kg/m2), and underweight (BMI < 20 kg/m2) were associated with
      higher mortality in all cohorts. Compared with overweight, the risk of death
      among those with obesity (BMI >= 30 kg/m2) varied depending on the population
      studied: HR (95% confidence interval) in those without CVD, with stable CVD, and
      with ACS were 1.20 (1.01 to 1.45; p = 0.04), 1.08 (1.02 to 1.15; p = 0.01), and
      1.01 (0.93 to 1.10; p = 0.72), respectively. The BMI associated with lowest
      mortality increased as cohort risk increased (no-CVD 27.2 kg/m2, stable CVD 28.1
      kg/m2, and ACS 30.9 kg/m2; p <0.001). Within each cohort, the optimal BMI value
      was higher in the high-risk subgroup. In the ACS cohort, low-risk patients had an
      optimal BMI value of 29.1 kg/m2 while in the high-risk group higher BMI was
      associated with lower risk of death (interaction-p <0.001). In conclusion,
      between and within cohorts of people without CVD, stable CVD, and ACS, higher BMI
      was associated with lower risk of death in higher risk groups. The benefits of
      increased body fat (i.e., increased caloric reserve) may counteract the hazards
      in high-risk groups, suggesting an alternative explanation of the obesity
      paradox.

PMID- 30107908
TI  - Oxicam-derived non-steroidal anti-inflammatory drugs suppress 1-methyl-4-phenyl
      pyridinium-induced cell death via repression of endoplasmic reticulum stress
      response and mitochondrial dysfunction in SH-SY5Y cells.
AB  - We have previously reported that oxicam-derived non-steroidal anti-inflammatory
      drugs (oxicam-NSAIDs), including meloxicam, piroxicam and tenoxicam, elicit
      protective effects against 1-methyl-4-phenyl pyridinium (MPP+)-induced cell death
      in a fashion independent of cyclooxygenase (COX) inhibition. We have also
      demonstrated that oxicam-NSAIDs suppress the decrease in phosphorylation of Akt
      caused by MPP+. The molecular mechanism through which oxicam-NSAIDs provide
      cytoprotection remains unclear. In this study, we speculated a possibility that
      endoplasmic reticulum (ER) stress and/or mitochondrial dysfunction, which are
      both causative factors of Parkinson's disease (PD), may be involved in the
      neuroprotective mechanism of oxicam-NSAIDs. We demonstrated here that oxicam
      NSAIDs suppressed the activation of caspase-3 and cell death caused by MPP+ or ER
      stress-inducer, tunicamycin, in SH-SY5Y cells. Furthermore, oxicam-NSAIDs
      suppressed the increases in the ER stress marker CHOP (apoptosis mediator) caused
      by MPP+ or tunicamycin, beside suppressing eukaryotic initiation factor 2alpha
      (eIF2alpha) phosphorylation and the increase in ATF4 caused by MPP+. Taken
      together, these results suggest that oxicam-NSAIDs suppress the eIF2alpha-ATF4
      CHOP pathway, one of the three signaling pathways in the ER stress response.
      Oxicam-NSAIDs suppressed the decrease in mitochondrial membrane potential
      depolarization caused by MPP+, indicating they also rescue cells from
      mitochondrial dysfunction. Akt phosphorylation levels were suppressed after the
      incubation with MPP+, whereas phosphorylation of eIF2alpha was enhanced. These
      results suggest that oxicam-NSAIDs prevented eIF2alpha phosphorylation and
      mitochondrial dysfunction by maintaining Akt phosphorylation (reduced by MPP+),
      thereby preventing cell death.

PMID- 30107909
TI  - Structural insights into inhibitor binding to a fungal ortholog of aspartate
      semialdehyde dehydrogenase.
AB  - The aspartate pathway, uniquely found in plants and microorganisms, offers novel
      potential targets for the development of new antimicrobial drugs. Aspartate
      semialdehyde dehydrogenase (ASADH) catalyzes production of a key intermediate at
      the first branch point in this pathway. Several fungal ASADH structures have been
      determined, but the prior crystallization conditions had precluded complex
      formation with enzyme inhibitors. The first inhibitor-bound and cofactor-bound
      structures of ASADH from the pathogenic fungi Blastomyces dermatitidis have now
      been determined, along with a structural and functional comparison to other ASADH
      family members. The structure of this new ASADH is similar to the other fungal
      orthologs, but with some critical differences in the orientation of some active
      site functional groups and in the subunit interface region. The presence of this
      bound inhibitor reveals the first details about inhibitor binding interactions,
      and the flexible orientation of its aromatic ring provides helpful insights into
      the design of potentially more potent and selective antifungal compounds.

PMID- 30107911
TI  - IL-13 and IL-13Ralpha1 are overexpressed in extranodal natural killer/T cell
      lymphoma and mediate tumor cell proliferation.
AB  - Extranodal NK/T cell lymphoma (NKTCL) is a rare but aggressive subtype of non
      Hodgkin lymphoma. Multi-agent chemotherapy and involved-field radiotherapy are
      used to treat this disease, but the prognosis remains poor. Interleukin 13 and
      its receptors (IL-13Rs) are correlated with the pathogenesis and progression of
      various malignances. However, their roles in NKTCL have not been evaluated. In
      this study, we examined the roles of IL-13 and IL-13Rs in NKTCL and the
      underlying mechanisms. We found significantly higher serum IL-13 levels (p <
      0.001) and IL-13Ralpha1 expression in tumor tissues (36 of 40, p < 0.001) in
      patients with NKTCL than in control cohort. IL-13 secretion was observed in tumor
      tissues (30 of 40, p < 0.001) and several cell lines of NKTCL. However, we did
      not detect significant associations between clinical characteristics and the
      expression levels of IL-13 or IL-13Rs. In vitro, IL-13 activated Stat6 and
      promoted cell proliferation in a dose-dependent manner. In addition, blocking IL
      13 exerted a negative effect on tumor cell growth. We conclude that IL-13
      functions as an autocrine growth factor in NKTCL and contributes to its
      pathogenesis. Blocking IL-13 is thus a potential therapeutic approach for NKTCL.

PMID- 30107910
TI  - Ubiquinol promotes retinal ganglion cell survival and blocks the apoptotic
      pathway in ischemic retinal degeneration.
AB  - Coenzyme Q10 (CoQ10) protects retinal ganglion cells (RGCs) in experimental
      retinal ischemia and glaucoma by scavenging reactive oxygen species. We tested
      whether a diet supplemented with ubiquinol, the reduced form of CoQ10, promotes
      RGC survival and blocks the apoptotic pathway in ischemic mouse retina induced by
      acute high intraocular pressure (IOP) elevation. Ubiquinol (1%) treatment
      significantly promoted RGC survival at 2 weeks after ischemia/reperfusion. The
      ubiquinol treatment significantly blocked activation of astroglial and microglial
      cells in the ischemic retina at 2 weeks. While the ubiquinol treatment
      significantly decreased active Bax protein expression in the ischemic retina,
      phosphorylation of Bad at serine 112 and Bcl-xL protein expression were preserved
      in the ubiquinol-treated ischemic retina at 12 h. Consistently, the ubiquinol
      treatment prevented apoptotic cell death by blocking caspase-3 cleavage. These
      results suggest that the ubiquinol enhances RGC survival by modulating the
      Bax/Bad/Bcl-xL-mediated apoptotic pathway in the ischemic retina. Ubiquinol has
      therapeutic potential for ameliorating elevated IOP-induced ischemic retinal
      degeneration.

PMID- 30107912
TI  - Crystal structure of the nicotinamidase/pyrazinamidase PncA from Bacillus
      subtilis.
AB  - The nicotinamidase/pyrazinamidase PncA is a member of a large family of hydrolase
      enzymes that catalyze the deamination of nicotinamide to nicotinic acid. PncA
      also functions as a pyrazinamidase in a wide variety of eubacteria and is an
      essential coenzyme in many cellular redox reactions in living systems. We report
      the crystal structure of substrate-free PncA from Bacillus subtilis (BsPncA) at
      2.0 A resolution to improve our understanding of the PncA family. The structure
      of BsPncA consists of an alpha/beta domain and a subdomain. The subdomain of
      BsPncA has a different conformation than that of PncA enzymes from other
      organisms. The B-factor analysis revealed a rigid structure of the alpha/beta
      domain, while the subdomain is highly flexible. Both dimers and tetramers were
      observed in BsPncA protein crystals, but only dimers were observed in solution.
      Our results provide useful information that will further enhance our
      understanding of the molecular functions of PncA family members.

PMID- 30107913
TI  - Long noncoding RNA LUCAT1 promotes malignancy of ovarian cancer through
      regulation of miR-612/HOXA13 pathway.
AB  - Emerging evidence shows that long noncoding RNA (lncRNA) is implicated in
      numerous kinds of malignant cancers, including ovarian cancer. In this study, we
      focused on the expression and function of long noncoding RNA lung cancer
      associated transcript 1 (LUCAT1) in ovarian cancer progression. We indicated that
      LUCAT1 expression was significantly upregulated in ovarian cancer tissues.
      Moreover, LUCAT1 expression was positively associated with tumor metastasis and
      clinical stage. Elevated expression of LUCAT1 decreased the survival rate of
      patients with ovarian cancer. In addition, we revealed that repression of LUCAT1
      significantly suppressed the proliferation, migration and invasion, whereas
      promoted apoptotic rate. Through online predictive tools and functional
      experiments, we demonstrated that LUCAT1 and HOXA13 were targets of miR-612. We
      showed that LUCAT1 and miR-612 suppressed each other in a reciprocal way.
      Moreover, LUCAT1 promoted HOXA13 expression through inhibition of miR-612,
      eventually leading to ovarian cancer development. In conclusion, our findings
      revealed a novel molecular mechanism that LUCAT1/miR-612/HOXA13 pathway modulates
      ovarian cancer progression.

PMID- 30107914
TI  - Adiponectin inhibits osteoclastogenesis by suppressing NF-kappaB and p38
      signaling pathways.
AB  - Adiponectin (APN) has been shown to play a key role in regulating bone mineral
      density (BMD). Nevertheless, the effects of APN on receptor activator of NF
      kappaB ligand (RANKL)-induced osteoclast formation and mechanism of regulation
      are not entirely clear. The study, therefore, aimed to evaluate the effect of APN
      on osteoclastogenesis. Our results showed that APN inhibits osteoclastogenesis
      and resorption function in vitro by suppressing nuclear factor-kappaB (NF-kappaB)
      and p38 signaling pathways, which is essential for osteoclast formation.
      Moreover, APN blocked the formation of F-actin rings and attenuated osteoclast
      mediated bone resorptive function. Therefore, we concluded that APN may provide a
      potential treatment for osteoclast-related diseases, such as osteoporosis.

PMID- 30107915
TI  - The C-terminus of ubiquitin plays a critical role in deamidase Lpg2148
      recognition.
AB  - By bearing a papain-like core structure and a cysteine-based catalytic triad,
      deamidase can convert glutamine to glutamic acid or asparagine to aspartic acid
      to modify the functions of host target proteins resulting in the blocking of
      eukaryotic host cell function. Legionella pneumophila effector Lpg2148 (MvcA) is
      a deamidase, a structural homolog of cycle inhibiting factor (Cif) effectors.
      Lpg2148 and Cif effectors are functionally diverse, with Lpg2148 only catalyzing
      ubiquitin but not NEDD8. However, a detailed understanding of substrate
      specificity is still missing. Here, we resolved the crystal structure of Lpg2148
      at 2.5 A resolution and obtained rigid-body modeling of Lpg2148 with C-terminus
      deleted ubiquitin (1-68) (ubDeltac) complex using HADDOCK, which shows that the C
      terminus of ubiquitin is flexible in recognition. We also conducted the truncated
      analysis to demonstrate that Leu71 of ubiquitin is necessary for its interaction
      with Lpg2148. Moreover, Val33 of Lpg2148 at the edge of a channel plays a vital
      role in the interaction and is limited by the length of the C-terminus of
      ubiquitin, which may help to explain the selectivity of ubiquitin over NEDD8. In
      summary, these results enrich our knowledge of substrate recognition of
      deamidase.

PMID- 30107916
TI  - CTCF is required for maintenance of auditory hair cells and hearing function in
      the mouse cochlea.
AB  - Auditory hair cells play an essential role in hearing. These cells convert sound
      waves, mechanical stimuli, into electrical signals that are conveyed to the brain
      via spiral ganglion neurons. The hair cells are located in the organ of Corti
      within the cochlea. They assemble in a special arrangement with three rows of
      outer hair cells and one row of inner hair cells. The proper differentiation and
      preservation of auditory hair cells are essential for acquiring and maintaining
      hearing function, respectively. Many genetic regulatory mechanisms underlying
      hair-cell differentiation and maintenance have been elucidated to date. However,
      the role of epigenetic regulation in hair-cell differentiation and maintenance
      has not been definitively demonstrated. CTCF is an essential epigenetic component
      that plays a primary role in the organization of global chromatin architecture.
      To determine the role of CTCF in mammalian hair cells, we specifically deleted
      Ctcf in developing hair cells by crossing Ctcffl/fl mice with Gfi1Cre/+ mice.
      Gfi1Cre; Ctcffl/fl mice did not exhibit obvious developmental defects in hair
      cells until postnatal day 8. However, at 3 weeks, the Ctcf deficiency caused
      intermittent degeneration of the stereociliary bundles of outer hair cells,
      resulting in profound hearing impairment. At 5 weeks, most hair cells were
      degenerated in Gfi1Cre; Ctcffl/fl mice, and defects in other structures of the
      organ of Corti, such as the tunnel of Corti and Nuel's space, became apparent.
      These results suggest that CTCF plays an essential role in maintaining hair cells
      and hearing function in mammalian cochlea.

PMID- 30107918
TI  - Shuffling the cards won't change your hand: Reclassifying congenital heart
      surgery cases by complexity.

PMID- 30107917
TI  - How to bridge? Management of anticoagulation in patients with mechanical heart
      valves undergoing noncardiac surgical procedures.

PMID- 30107919
TI  - The Ross procedure: Time to reevaluate the guidelines.

PMID- 30107920
TI  - Make sternotomy great again.

PMID- 30107921
TI  - We are what we eat.

PMID- 30107922
TI  - The answer to the great question.

PMID- 30107923
TI  - The fourth dimension.

PMID- 30107924
TI  - MAC: "Mitral annular calcification" or a "modern approach to concept learning" in
      surgery.

PMID- 30107925
TI  - Venous valve saves the day for a patient with single ventricle and
      atrioventricular valve disease.

PMID- 30107926
TI  - Adjuvant chemotherapy in stage I lung cancer: Is more better?

PMID- 30107927
TI  - Personalized cardiac surgery: Can noninvasive flow imaging lead to individualized
      resection strategies for bicuspid aortopathy?

PMID- 30107928
TI  - Interventional radiology suite or hybrid operating room: Which is the best for
      lung nodule localization?

PMID- 30107929
TI  - Isolated mechanical aortic valve replacement in rheumatic patients in a low- to
      middle-income country.
AB  - OBJECTIVE: Although the results of aortic valve replacement are well documented
      for industrialized countries, the outcome in patients with rheumatic aortic valve
      disease in low- to middle-income countries is less well explored. The aim of this
      study was to determine the long-term survival and clinical outcomes after
      isolated aortic valve replacement in patients with rheumatic heart disease in a
      Sub-Saharan country where follow-up of indigent patients is often challenging.
      METHODS: A retrospective review of 969 aortic valve replacements performed
      between 2003 and 2013 was conducted at Cape Town's Groote Schuur Hospital.
      Patients who underwent concomitant procedures (n = 664) or had nonrheumatic valve
      pathology (n = 185) were excluded. The mean age of the rheumatic cohort (n = 121)
      was 43.1 +/- 11.6 years with a mean follow-up period of 6.14 +/- 3.44 years. The
      primary end points were survival and valve-related complications. RESULTS: A 15%
      cardiac- or valve-related 10-year mortality after receiving a mechanical
      prosthesis corresponded with a significantly higher mortality rate than that of a
      matched population. Overall cumulative survival at 1, 5, and 10 years was 93.5%
      (87.0-96.9), 86.4% (78.4-91.8), and 78.1% (67.5-86.0), respectively, and the
      corresponding cumulative freedom from combined thromboembolism and bleeding was
      94.4% (88.2-97.5), 87.4% (79.4-92.5), and 86.1% (77.9-91.6), respectively.
      CONCLUSIONS: In low- to middle-income countries, with their unique mix of
      indigent and "First World" patients, rheumatic heart disease still accounts for a
      significant proportion of patients requiring isolated aortic valve replacement.
      Although mechanical prostheses are often selected in these young adults, survival
      remains suboptimal. Major bleeding and thromboembolic events account for the
      majority (77%) of the reported valve-related complications.

PMID- 30107930
TI  - Using 3-dimensional printing technology to deliver patient-centered care.

PMID- 30107931
TI  - Respectful resection to enhance the armamentarium of mitral valve repair: Is less
      really more?

PMID- 30107932
TI  - Absence of complement factor H alters bone architecture and dynamics.
AB  - Complement system is an important arm of the immune system that promotes
      inflammation. Complement Factor H (FH) is a critical regulator of the alternative
      complement pathway. Its absence causes pathology in different organs resulting in
      diseases such as age related macular degeneration and dense deposit disease.
      Recent studies suggest that the complement system plays a role in bone
      development and homeostasis. To determine the role of FH in bone architecture, we
      studied the FH knockout (fh-/-) mice. 3D reconstructions of femur from 16 week
      old fh-/- mice reveal significant changes, such as decreased BV/TV (4.5%, p <
      0.02), trabecular number (22%, p < 0.01), tissue mineral density (16%, p < 0.04),
      and increased marrow area (16% p < 0.01), compared to their wild type (WT)
      counterparts. Kidney function and histology remained normal indicating that bone
      changes occurred prior to kidney dysfunction. Next we examined cultured
      osteoblasts and osteoclasts isolated from bone marrow. FH is expressed
      ubiquitously in the osteoblasts and in the cytoplasm of osteoclasts. The changes
      caused by absence of FH include: increase in number of osteoblasts (362%) and
      osteoclasts (342%), increase in RNA (180%) and protein expression of cathepsin K
      and increased osteoclast function (pit formation, 233%). Actin rearrangement in
      both osteoblasts and osteoclasts was altered, with a loss of integrity of the F
      actin ring at the periphery of the osteoclasts. For the first time our studies
      demonstrate a direct role of FH in the maintenance of bone structure and function
      and is highlighted as a promising therapeutic target in bone diseases.

PMID- 30107933
TI  - Serum neuropeptide concentrations in cows with intrapartum uterine torsion.
AB  - Intrapartum uterine torsion is a common cause of dystocia in dairy cows. To
      clarify the pathophysiology of this disease, the aim of the present study was to
      examine serum neuropeptide and cytokine concentrations of cows with intrapartum
      uterine torsion. Blood samples of 20 cows with uterine torsion, 36 healthy
      controls, and 15 intrapartum cows without uterine torsion were obtained.
      Concentrations for substance P (SP), vasoactive intestinal polypeptide (VIP), and
      interleukin-1beta (IL-1beta) were quantified by using commercially available
      ELISA kits. Significant differences between groups were observed for SP in cows
      with uterine torsion and cows calving normally (P <  0.01). Markedly greater SP
      concentrations were observed in calving cows than in cows with uterine torsion.
      Compared with healthy controls, there were greater SP concentrations during
      parturition (P <  0.01). No significant group differences were detected for VIP
      concentrations. Global differences were observed in IL-1beta (P =  0.04). Large
      amounts of SP are released into the blood during parturition. Because SP is
      mainly present within the cervix and functions as a biomarker and mediator of
      pain, cows with uterine torsion are presumed to not experience as much pain as
      cows that are calving normally. Consistent with this, in cows with uterine
      torsion, there is a disturbance in the opening of the cervix, along with only
      mild signs of colic. Furthermore, significantly elevated IL-1beta concentrations
      correlate with the inflammation that occurs in cases of uterine torsion. Further
      research is needed to support these findings and clarify the clinical relevance.

PMID- 30107934
TI  - Serum progesterone concentrations during FSH superstimulation of the first
      follicular wave affect embryo production in sheep.
AB  - The aim of the present study was to evaluate the effect of serum progesterone
      concentrations during the superstimulatory treatment of the first follicular wave
      on fertilization rate and embryo development in sheep. A total of 71 Merino ewes
      received a superstimulatory FSH treatment during Wave 1 of ovarian follicular
      development (Day 0 Protocol), which was administrated under low progesterone
      concentrations typical of the early luteal phase (control group, n = 33) or under
      high progesterone concentrations induced by the administration of an intravaginal
      device from Day 0 to Day 3 containing 0.3 g progesterone (n = 38). Intrauterine
      insemination after FSH superstimulation was followed by uterine flushing 6 days
      later. Serum progesterone concentrations from Day 0 to 3 were greater in those
      ewes treated with progesterone (P < 0.05), while serum estradiol-17beta
      concentrations were not affected by the treatment. Although the mean number of
      corpora lutea per donor was not affected by the progesterone treatment, the
      number of collected ova and embryos was greater in progesterone treated than
      untreated ewes (6.6 +/- 0.7 compared with 4.6 +/- 0.9, respectively; P < 0.05).
      Furthermore, progesterone treatment increased fertilization rate (93.3% compared
      with 83.3%; P < 0.05) and the proportion of Grade 1 embryos (67.7% compared with
      52.7%; P < 0.05) compared with the control group. In conclusion, oocyte
      fertilization rate and embryo quality are improved by high progesterone
      concentrations during FSH superstimulation, which suggests an important role of
      progesterone during preovulatory follicular development.

PMID- 30107935
TI  - [ENT benign lesions and pseudo-tumors: Case No. 1].

PMID- 30107936
TI  - Clinical features of a sample of inpatients with adjustment disorder referred to
      a consultation-liaison psychiatry service over 10 years.

PMID- 30107937
TI  - Effectiveness of Therapeutic Exercise on Forward Head Posture: A Systematic
      Review and Meta-analysis.
AB  - OBJECTIVE: The purpose of this systematic review and meta-analysis was to
      summarize the results related to the effects of corrective exercises on postural
      variables in individuals with forward head posture (FHP). METHODS: A systematic
      review of the electronic literature through February 2017 was independently
      performed by 2 investigators. The electronic databases searched included PubMed,
      MEDLINE, Web of Science, ScienceDirect, Cochrane Central Register of Controlled
      Clinical Trials, Google Scholar, and Scopus. Methodological quality was evaluated
      using the Physiotherapy Evidence Database scale. Meta-analyses were carried out
      for craniovertebral angle (CVA), cranial angle (CA), and pain intensity. RESULTS:
      Seven randomized clinical trials comprising 627 participants met the study
      criteria. The between-groups pooled random odds ratios for CVA, CA, and pain were
      6.7 (confidence interval [CI] = 2.53-17.9, P = .0005), 0.7 (CI = 0.43-1.2, P =
      .2), and 0.3 (95% CI = 0.13-0.42, P < .001), respectively. No publication bias
      was observed. Level 1a evidence (strong) indicates exercise training can
      effectively modify CVA, and level 1b evidence (moderate) indicates exercise may
      improve pain but not CA. CONCLUSION: The findings suggest that therapeutic
      exercises may result in large changes in CVA and moderate improvement in neck
      pain in participants with FHP. The precise nature of the relationship between FHP
      and musculoskeletal pain, and improvements in both after therapeutic exercise,
      remains to be established.

PMID- 30107938
TI  - Validation of the Neck Disability Index in Serbian Patients With Cervical
      Radiculopathy.
AB  - OBJECTIVE: The purpose of this study was to translate the Neck Disability Index
      into the Serbian language (NDI-S) and to investigate the validity of this version
      for use in Serbian population. METHODS: Fifty patients with cervical
      radiculopathy were enrolled in the study and completed a multidimensional
      questionnaire, including NDI-S. Inclusion criteria were ages between 18 and 65
      years, Serbian speaking, no cognitive or hearing impairment, sharp and radiating
      neck and upper extremity pain that has lasted less than 12 months, radiculopathy
      signs evaluated by electromyoneurography and disc herniation, or spondylotic
      changes of cervical spine visualized on magnetic resonance imaging. Exclusion
      criteria were malignancy, previous cervical spine discectomy, trauma of the
      cervical spine and myelopathy, polyneuropathy, fibromyalgia, and psychiatric
      disorders. Validity was determined by the correlation of the Neck Disability
      Index, with pain measured by visual analogue scale, characteristics related to
      pain, and mental status. Also, factor structure of NDI-S was explored through
      factor analysis. Reliability was assessed through internal consistency
      (Cronbach's alpha and item-total correlations). RESULTS: Correlation analysis
      between pain and NDI-S showed significant values (P < .01). The NDI-S correlated
      well with patients mental status (r = 0.421, P < .01). Cronbach's alpha of NDI-S
      was 0.85, denoting excellent internal consistency of the questionnaire. Item
      total correlations were significant and ranged from 0.328 to 0.789. Factor
      analysis demonstrated a 2-factor structure with an explained variance of 55%.
      CONCLUSION: The NDI-S is a valid questionnaire to measure neck and arm pain
      related to disability in Serbian patients with cervical radiculopathy.

PMID- 30107939
TI  - Adolescent smoking and the social capital of local communities in three counties
      in Romania.
AB  - OBJECTIVE: To identify the effect of social capital on adolescent smoking.
      METHOD: A stratified random sample of 1313 7th and 8th grade students from three
      counties in Transylvania, Romania, completed a self-administered questionnaire on
      smoking-related knowledge, attitudes and behaviours. The impact of social capital
      was measured (personal and community activities, school achievements and smoking
      related knowledge). Multivariate multinomial logistic regression models were used
      to measure the association between social participation and smoking. RESULTS:
      Experimenting with smoking was mostly related to knowledge about smoking,
      academic performance and second-hand tobacco smoke exposure at home. The
      strongest risk factor of adolescent smoking was the smoking behaviour of
      classmates: those who reported a significant proportion of smokers among their
      classmates were nine times more likely to smoke themselves than in other cases
      (adjusted odds ratio [aOR]: 9.05). Those who considered smoking to be harmless
      were 4 times more likely to be smokers than those who considered this behaviour
      to be dangerous (aOR: 4.28). Poor academic results increased adolescents' smoking
      (aOR: 3.22 and 2.66). The odds were significantly higher for smoking, if they had
      an active social life (aOR: 2.54). Regular church attendance proved to be a
      protective factor (aOR: 0.45). CONCLUSIONS: Several social capital factors can
      play a role in adolescent smoking. The organization and the development of
      community activities aimed at prevention must strengthen the factors related to
      the community's social capital to reduce the likelihood of teenage smoking.

PMID- 30107940
TI  - Clinical experience of optimising thiopurine use through metabolite measurement
      in inflammatory bowel disease.
AB  - INTRODUCTION: Thiopurine therapy can be optimised by determining the
      concentration of the drug's metabolites. PATIENTS AND METHODS: Retrospective
      analysis on a prospective database of 31 patients with inflammatory bowel disease
      who failed therapy with thiopurines. Thiopurine metabolites (6-thioguanine, 6-TGN
      and 6-methylmercaptopurine, 6-MMP) were measured by high-performance liquid
      chromatography (Laboratorios Cerba, Barcelona) and treatment was duly adjusted in
      accordance with the results. Clinical response was reassessed after six months.
      RESULT: Despite the appropriate theoretical dose of thiopurines being
      administered, the dose was insufficient in 45.6% of patients (nonadherence to
      treatment suspected in 6.45%) and 16.2% received an excessive dose or the drug
      was metabolised by other metabolic pathways. After treatment was optimised based
      on metabolite levels, only 25.8% (8/31) were prescribed a biological agent, while
      74.2% of cases (23/31) were managed through dose optimisation alone. DISCUSSION:
      Monitoring thiopurine metabolite levels may help clinicians to assess non
      responsive patients before adding or switching to another drug (generally a
      biological agent), thereby avoiding any additional costs or potential toxicity.
      This strategy may also help to identify patients receiving an insufficient dose
      and those with an alternative metabolic pathway, who could be candidates for low
      dose AZA with allopurinol, as well as patients who are suspected of being non
      adherent. In three out of four patients, switching to a biological agent can be
      avoided.

PMID- 30107941
TI  - [Seasonal flu vaccination for older people: Evaluation of the quadrivalent
      vaccine. Positioning report].
AB  - Influenza is a significant health problem, particularly in those persons
      susceptible to having associated complications, older people, children less than
      2 years, patients with chronic diseases, immunocompromised patients, and pregnant
      women. But influenza also has a large impact on the health system, with an
      increase in the healthcare demand and a spectacular increase in outpatient
      visits, overloading the emergency and hospital services. During epidemic
      outbreaks, the hospital admission rates of people over 65 years are at a maximum,
      and the mortality notified for the 2017/2018 influenza season was 960 deaths. The
      seasonal anti-influenza vaccine is the method with a better cost-effective ratio
      of primary prevention of influenza, reducing associated respiratory diseases, the
      number of hospital admissions, and deaths in high risk individuals, as well as
      work absenteeism in adults. In the last few years, influenza B has received
      little attention in the scientific literature, although in the periods between
      epidemics influenza B can be one of the main causes of seasonal epidemics,
      causing considerable morbidity and mortality and an increase in costs. The
      quadrivalent vaccine has a second-line immunological protection against influenza
      B, and according to a critical review of the scientific literature, it provides
      wider protection without affecting immunogenicity of the other three vaccine
      strains common to the trivalent and tetravalent vaccine. The quadrivalent vaccine
      is cost-effective in reducing the number of influenza cases, and is always a
      worthwhile intervention, with a significant cost saving for the health system and
      for society, by reducing the hospital admission rates and mortality associated
      with the complications of influenza. Supplement information: This article is part
      of a supplement entitled 'Seasonal flu vaccination for older people: Evaluation
      of the quadrivalent vaccine' which is sponsored by Sanofi-Aventis, S.A.

PMID- 30107942
TI  - Dysphagia in older persons following severe burns: Burn location is irrelevant to
      risk of dysphagia and its complications in patients over 75 years.
AB  - BACKGROUND: Management of burns in older persons is complex with evidence
      indicating advanced age is associated with elevated risk for morbidity and
      mortality. Dysphagia and its sequelae may further increase this risk. AIMS: (1)
      Determine the prevalence, and (2) identify risk factors for dysphagia in patients
      admitted with severe burn injury over 75 years. METHODS: All patients >75 years
      admitted to Concord Repatriation General Hospital with severe burn injury over a
      4-year period (2013-2017) were assessed for dysphagia on presentation and
      continually monitored throughout their admission. Burn injury, demographic and
      nutritional data were captured and analysed for association with and predictive
      value for dysphagia. RESULTS: Sixty-six patients (35 male; 31 female) aged 75-96
      years (median 82 years) were recruited. Dysphagia was identified in 46.97% during
      their hospital admission. Dysphagia was significantly associated with burn size,
      pre-existing cognitive impairment, mechanical ventilation, duration of enteral
      feeding, hospital length of stay, in-hospital complications and mortality. No
      association was identified between burn location, burn mechanism, surgery and
      dysphagia. Burn size and Malnutrition Screening Tool score were found to be
      independent predictors for dysphagia. CONCLUSIONS: Dysphagia prevalence is high
      in older persons with burns and is associated with increased morbidity and
      mortality, regardless of burn location.

PMID- 30107943
TI  - Factors affecting self-perceived participation and autonomy among patients with
      burns: A follow-up study.
AB  - OBJECTIVE: This study aimed to evaluate self-perceived participation and autonomy
      in patients with burns in Fujian, China, and to identify key factors influencing
      these parameters. METHODS: We investigated 212 patients admitted to the burns
      unit 1 and 3months after discharge using the Impact on Participation and Autonomy
      (IPA), Acceptance of Disability Scale-Revised, Herth Hope Index, Modified Barthel
      Index Rating Scale, Visual Analogue Scale, and a self-designed demographic data
      and disease condition questionnaires. Influencing factors were identified using
      multivariable linear regression. RESULTS: The general IPA questionnaire scores
      were 2.13+/-0.74 and 2.03+/-0.72 at 1 and 3months post-discharge, respectively.
      Acceptance of disability, hope, and social participation were significantly
      correlated (P<0.01). Financial situation, pain level, activities of daily living,
      acceptance of disability, and hope were major factors affecting self-perceived
      participation and autonomy 3months post-discharge, accounting for a variance of
      77.5%. CONCLUSION: Medium-to-low levels of self-perceived participation and
      autonomy were observed 1 and 3months post-discharge. Clinicians should adopt
      specific measures to help patients (including those from poor economic
      backgrounds) successfully reintegrate into their families/societies. These
      include alleviating their pain, encouraging participation in daily activities
      while accepting their disabilities, and offering hope.

PMID- 30107944
TI  - Reprint of: Efficacy, tolerability, and safety of non-pharmacological therapies
      for chronic pain: An umbrella review on various CAM approaches.
AB  - BACKGROUND: Complementary and alternative medicine (CAM) therapies may be used as
      a non-pharmacological approach to chronic pain management. While hundreds of
      trials about individual CAM modality have been conducted, a comprehensive
      overview of their results is currently lacking for pain clinicians and
      researchers. AIM: This umbrella review synthesized the quality of meta-analytic
      evidence supporting the efficacy, tolerability and safety of CAM therapies for
      the management of chronic pain. MATERIALS & METHODS: MEDLINE, EMBASE, CINAHL, and
      CENTRAL were searched from October 1991 to November 2016. Reviews of clinical
      trials (randomized and non-randomized) with meta-analysis investigating the
      utility of any CAM modality for chronic pain were eligible. Pain relief post
      intervention was the main outcome and secondary outcomes included patients'
      adherence and incidence of adverse effects during CAM protocol. RESULTS: Twenty
      six reviews (207 clinical trials, >12,000 participants) about 18 CAM modalities,
      falling under natural products, mind and body practices or other complementary
      health approaches were included. Inhaled cannabis, graded motor imagery, and
      Compound Kushen injection (a form of Chinese medicine) were found the most
      efficient (with moderate-to-high effect sizes and low heterogeneity) and
      tolerable (>=80% of adherence to study protocols) for chronic pain relief. When
      reported, adverse effects related to these CAM were minor. CONCLUSION: Although
      several CAM were found effective for chronic pain relief, it remains unclear when
      these modalities are a reasonable choice against or in conjunction with
      mainstream treatments. In that sense, future research with a clear emphasis on
      concurrent evaluation of CAM overall efficacy and patient adherence/tolerance is
      needed.

PMID- 30107945
TI  - Interval colorectal cancer after colonoscopy.
AB  - INTRODUCTION AND AIMS: Interval colorectal cancer (iCRC) can occur due to missed
      lesions or to a newly developed lesion. The present study aimed to assess the
      iCRC rate and its characteristics in our population and find possible
      explanations. MATERIALS AND METHODS: A retrospective study was conducted on
      patients with colorectal cancer (CRC) diagnosed between January 2011 and January
      2015 at our department. Demographics, endoscopic data, and tumor characteristics
      (location, histology, staging) were collected. We identified patients diagnosed
      with CCR who underwent colonoscopy at our department in the previous 10years and
      presented the disease (iCRC) before the date of their next recommended exam. The
      cases of iCRC were characterized and compared with other CRC cases. Possible
      explanations for the appearance of iCRC were analyzed. RESULTS: A total of 266
      patients presented with CRC, 61.7% were men, and mean patient age was 70.7years.
      We identified 10 patients with iCRC: 6 were men, and mean patient age was
      71.1years. Mean time for iCRC diagnosis after index colonoscopy was 3.5+/
      1.84years. Tumor was located in the right colon in 50% of the patients with iCRC
      and in 24.5% of the patients without iCRC (P=.091). More patients with iCRC had a
      family history of CRC (50%) than the patients with reference CRC (3.1%) (P=.000).
      CONCLUSIONS: In our case series, 3.76% of all CRC were iCRC. There were no
      statistically significant differences between patients with or without iCRC, with
      the exception of family history of CRC.

PMID- 30107946
TI  - Non-Invasive Mechanical Ventilation Versus Continuous Positive Airway Pressure in
      Cardiogenic Pulmonary Edema in an Intensive Care Unit.

PMID- 30107947
TI  - Fractional flow reserve in acute coronary syndromes and in stable ischemic heart
      disease: clinical implications.
AB  - BACKGROUND: Fractional Flow Reserve (FFR) in Stable Ischemic Heart Disease (SIHD)
      is universally accepted, while in Acute Coronary Syndromes (ACS) is less
      established. Aims of this retrospective study were: to compare in patients
      undergoing FFR assessment the prognostic impact of ACS vs SIHD, to evaluate the
      clinical relevance of the modality of utilization and timing of FFR assessment
      and to assess the different outcomes associated with an FFR> or <=0.80. METHODS:
      Major cardiac adverse events were assessed at a follow up of 16.4 +/- 10.5 months
      in 543 patients with SIHD and 231 with ACS needing functional evaluation. FFR was
      used for lesions of ambiguous significance in the absence of a clear culprit
      vessel (first intention, FI) and for incidental lesions in the presence of a
      clear culprit vessel (second intention, SI). The decision to perform FFR and the
      identification of the stenosis needing functional assessment were left to the
      operator's discretion. Revascularization was performed when FFR was <=0.80.
      RESULTS: SIHD and ACS patients were not significantly different for principal
      clinical characteristics. ACS patients had significantly more events than SIHD,
      due to an excess of death and myocardial infarction. This was confirmed when FFR
      was used as FI, in particular if FFR was >0.80. On the contrary, when FFR was
      used as SI, event rates were similar between ACS and SIHD patients, regardless of
      FFR value. CONCLUSIONS: Our study shows that using FFR the risk of recurrent
      events in ACS is significantly higher than in SIHD. This different outcome is
      confined to those patients in whom FFR is utilized for lesions of ambiguous
      significance in the absence of a clear culprit vessel.

PMID- 30107948
TI  - Geometric and dosimetric evaluation of atlas based auto-segmentation of cardiac
      structures in breast cancer patients.
AB  - BACKGROUND AND PURPOSE: Auto-segmentation represents an efficient tool to segment
      organs on CT imaging. Primarily used in clinical setting, auto-segmentation plays
      an increasing role in research, particularly when analyzing thousands of images
      in the "big data" era. In this study we evaluate the accuracy of cardiac
      dosimetric endpoints derived from atlas based auto-segmentation compared to gold
      standard manual segmentation. MATERIAL AND METHODS: Heart and cardiac
      substructures were manually delineated on 54 breast cancer patients. Twenty-seven
      patients were used to build the auto-segmentation atlas, the other 27 to validate
      performance. We evaluated accuracy of the auto-segmented contours with standard
      geometric indices and assessed dosimetric endpoints. RESULTS: Auto-segmented
      contours overlapped geometrically with manual contours of the heart and chambers
      with Dice-similarity coefficients of 0.93 +/- 0.02 (mean +/- standard deviation)
      and 0.79 +/- 0.07 respectively. Similarly, there was a strong link between
      dosimetric parameters derived from auto-segmented and manual contours (R2 = 0.955
      1.000). On the other hand, the left anterior descending artery had little
      geometric overlap (Dice-similarity coefficient 0.09 +/- 0.07), though acceptable
      representation of dosimetric parameters (R2 = 0.646-0.992). CONCLUSIONS: The
      atlas based auto-segmentation approach delineates heart structures with
      sufficient accuracy for research purposes. Our results indicate that quality of
      auto-segmented contours cannot be determined by geometric values only.

PMID- 30107949
TI  - Coping with mental health issues among older Hispanic adults.
AB  - Access to mental health services for older Hispanic adults is limited and often
      older Hispanic adults must rely on their own resources in dealing with mental
      health issues. The aim of this study was to understand how older Hispanic
      immigrants cope mental health issues (e.g. stress, anxiety, and/or depression). A
      qualitative, descriptive approach was used to interview 17 older Hispanic
      immigrants from Guatemala, Dominican Republic and Colombia. Interviews were audio
      recorded, transcribed and translated verbatim by bilingual research assistants.
      Data were analyzed using content analysis with a combination of
      immersion/crystallization, editing and template organizing styles. Ways of coping
      included spiritual beliefs and religious practices, social support, distraction,
      medications and professional help. Primary care providers may be more effective
      if they build upon the cultural constructs that undergird older Hispanic
      immigrants' ways of coping in addressing emotional distress and mental health
      issues in this population.

PMID- 30107950
TI  - About the EFforT-BCRL-trial...

PMID- 30107951
TI  - Everything the clinician needs to know about evidence-based anticoagulation in
      pregnancy.
AB  - Pregnancy is a hemostatic challenge: women are prone to thromboembolism during
      their pregnancy and at the same time, especially during delivery, there is
      substantial risk of bleeding. Pregnant women are often excluded from randomized
      controlled trials, and high quality evidence regarding optimal anticoagulant
      management is thus lacking. Anticoagulants are being used in pregnancy for
      prevention and treatment of various pregnancy complications such as thrombotic
      events, preeclampsia and pregnancy loss. When anticoagulant therapy is necessary,
      special attention should be given to both woman and unborn child. In this review,
      we aim to 1) provide an overview of safe anticoagulant use in pregnancy, 2)
      discuss treatment goals in pregnancy, and 3) summarize the evidence available to
      guide decision making for frequently encountered clinical dilemmas in this field.

PMID- 30107952
TI  - Equitable vaccination against human papillomavirus: the road ahead.

PMID- 30107954
TI  - Change of site of intra-articular injection of hypertonic dextrose resulted in
      different effects of treatment.
AB  - Most minimally invasive treatments for dysfunction of the temporomandibular joint
      (TMJ) are empirical, and aimed at the painful trigger points with the purpose of
      preventing muscular spasm and restoring normal function. In this prospective
      study I investigated whether the choice of site of injection of hypertonic
      dextrose affected the benefits of treatment of internal derangement and pain. I
      studied 72 patients with pain and clicking as a result of dysfunction of the TMJ.
      Patients were divided into four groups with four separate sites for intra
      articular injection. Dextrose was injected into the superior joint space,
      inferior joint space, retrodiscal tissue, and anterior capsule injection. Results
      showed that the retrodiscal site was the most effective for reducing clicking and
      subsequently improving derangement, while the inferior joint space was the best
      site for the relief of pain, and the extracapsular site should be used in cases
      of hypermobility. In conclusion, the injection site should be selected according
      to the symptoms being treated, and could be used as an adjunct to other sites to
      improve outcome.

PMID- 30107953
TI  - Complications and outcome after free flap surgery for cancer of the head and
      neck.
AB  - We retrospectively studied 136 patients who had free flap reconstruction for
      cancer of the head and neck at a single centre (2008-2015) to evaluate
      complications, assess factors associated with them, and analyse their impact on
      outcome. Preoperative and perioperative data, and surgical and medical
      complications were recorded, and the impact of the complications on duration of
      hospital stay and survival were assessed. A total of 86 (63%) patients had
      complications. Compared with those who did not, they had a higher rate of alcohol
      abuse (21/86, compared with 5/50, p=0.039), longer operations (median (IQR) 565
      (458-653 compared with 479 (418-556) minutes, p<0.001), and greater
      intraoperative loss of blood (725 (400-1150) compared with 525 (300-800) ml,
      p=0.042). Complications were more common in patients who had fibular flaps and T4
      disease (22/86 compared with 4/50, p=0.010; 47/80 compared with 16/47, p=0.015,
      respectively). Those who had complications also stayed in hospital longer (median
      (IQR) 9 (7-12) compared with 15 (10-21) days, p<0.001). Cumulative mortality was
      higher in patients with late complications (those that occurred after the fourth
      postoperative day) (61% compared with 36%, p=0.004). In conclusion, complications
      in more than half the patients were related to alcohol abuse, a more complicated
      intraoperative course, and fibular flaps. Complications were associated with a
      longer hospital stay, and survival was higher in those who did not have late
      complications than in those who did.

PMID- 30107955
TI  - Nephrotic syndrome in relation to treatment with ustekinumab.

PMID- 30107956
TI  - Acute kidney disease related to leptospirosis.

PMID- 30107957
TI  - Aortic Stenosis with Severe Tricuspid Regurgitation: Comparative Study between
      Conservative Transcatheter Aortic Valve Replacement and Surgical Aortic Valve
      Replacement Combined With Tricuspid Repair.
AB  - BACKGROUND: Severe aortic stenosis (AS) and severe tricuspid regurgitation (TR)
      may coexist. The aim of this study was to determine the change in right
      ventricular (RV) function and TR after surgical aortic valve replacement combined
      with tricuspid valve repair (SAVR+TVr), transcatheter aortic valve replacement
      (TAVR), or conservative management and compare outcomes dependent on RV
      functional parameters and treatment allocation. METHODS: A retrospective analysis
      was conducted in 147 consecutive patients with severe AS and TR of baseline and 6
      month clinical and echocardiographic parameters, including quantitative
      estimation of RV size and function (end-diastolic and end-systolic areas,
      tricuspid annular plane systolic excursion, fractional area change, and Tei
      index). RESULTS: SAVR+TVr and TAVR were associated with superior reduction in TR
      jet area after 6 months (P = .01 for time * group interaction) compared with
      conservative therapy. However, RV function (tricuspid annular plane systolic
      excursion and stroke volume) improved after TAVR but not after SAVR+TVr (P = .007
      and P = .02 for time * group interaction, respectively). Conservative therapy for
      combined AS and TR was associated with >80% mortality in <4 years. TAVR and
      SAVR+TVr were associated with improved survival compared with conservative
      therapy (P < .0001), without significant difference between each other.
      Quantitative RV functional parameters were associated with poor outcomes,
      including tricuspid annular plane systolic excursion (P = .002), Tei index (P =
      .02), and RV fractional area change (P = .03). CONCLUSIONS: In this
      nonrandomized, retrospective, observational study, SAVR+TVr and TAVR were
      associated with reductions in TR in patients with severe AS combined with severe
      TR. Importantly, RV function improved after TAVR but not after SAVR+TVr. Patients
      with severe AS and TR have a very poor prognosis with conservative therapy. When
      contemplating invasive procedures, assessment should include quantitative
      functional RV parameters.

PMID- 30107958
TI  - Outpatient Total Hip Arthroplasty Has Minimal Short-Term Complications With the
      Use of Institutional Protocols.
AB  - BACKGROUND: Interest in outpatient/same-day discharge (SDD) total hip
      arthroplasty (THA) has been increasing over the last several years. There is
      considerable debate in the literature regarding the complication and readmission
      rates of these patients. To evaluate and validate the safety and efficacy of our
      institutional SDD THA care pathway, we compared the outcomes of patients
      undergoing SDD THA with patients who had a similar comorbidity profile and
      underwent inpatient THA. METHODS: A retrospective review was conducted on 164
      patients who underwent SDD THA from January 2015 to September 2016. The Risk of
      Readmission Tool, a validated risk stratification instrument, was applied to all
      inpatient THAs performed from June 2014 to December 2016. A cutoff Risk of
      Readmission Tool score < 3 was used to produce a cohort of 1858 inpatient THA
      patients, all of whom had a similar risk profile to patients who underwent SDD
      THA. Medicare patients were excluded from the inpatient THA cohort, which left a
      final inpatient sample of 1315 patients. Each cohort was evaluated for
      demographic variables, length of stay, 30-/90-day readmissions, and discharge
      disposition. RESULTS: The SDD THA cohort had significantly lower body mass index
      (26.9 vs 28.2 kg/m2; P = .002), had fewer minorities (89.6% vs 66.3% Caucasians;
      P < .001), was exclusively commercial insurance (100% vs 36.3%), had a shorter
      length of stay (0.37 vs 2.3 days, P < .001), and was exclusively discharged home
      (100% vs 92.6%). There was no statistically significant difference in 30-day
      readmission rates between either cohort (SDD 0.6% vs inpatient 1.6%; P = .325).
      However, the SDD cohort had a significantly lower rate of 90-day readmissions
      than the inpatient cohort (0.6% vs 3.6%; P = .014). CONCLUSION: The use of an
      institutional SDD THA care pathway can produce results with equivalent or better
      short-term outcomes than that of traditional inpatient THA.

PMID- 30107959
TI  - Supporting Radiology Residents' Professional Development Through a Competitive
      Intramural Grant.
AB  - Research and other scholarly activities are an important and required component
      of diagnostic radiology training. Several strategies, both at the departmental
      and the larger organizational levels, have been implemented to encourage
      radiology trainees to participate in these activities. In this article, we review
      and discuss our institution's 10-year experience in supporting the development
      and realization of scholarly projects through a competitive intramural grant for
      residents.

PMID- 30107960
TI  - Rapid Diagnosis of KCNQ2-Associated Early Infantile Epileptic Encephalopathy
      Improved Outcome.

PMID- 30107961
TI  - Cortactin as a potential predictor of second esophageal neoplasia in
      hypopharyngeal carcinoma.
AB  - OBJECTIVE: Hypopharyngeal carcinoma has a very poor prognosis. The high incidence
      of second esophageal neoplasia is one of the major causes. To establish an
      efficient follow-up scheme for increasing the diagnostic yield and reducing the
      adverse impact of second esophageal neoplasia on survival, the purpose of this
      study was to explore a biomarker to predict second esophageal neoplasia. METHODS:
      In this retrospective cohort study, consecutive tissue specimens from those
      patients who underwent tumor resection between September 2007 and October 2015
      were collected. Gene amplification was performed by real-time PCR. The expression
      of cortactin was evaluated by immunohistochemistry. The predictive risk factors
      of developing second esophageal neoplasia and prognostic factors related to
      survival were analyzed. RESULTS: A total of 187 patients were included with a
      mean follow-up of 48months (12-118months). Second esophageal tumors were found in
      53 (28.3%), including 41 (21.9%) esophageal squamous cell carcinoma and 12 severe
      dysplasia. The results of multivariate analyses revealed that age (OR 2.81, 95%
      CI 1.16-6.78), cortactin overexpression (OR 2.49, 95% CI 1.17-5.33), and stage IV
      versus I (OR 6.49, 95% CI 1.68-25.18) were independent predictors of second
      esophageal neoplasia, and second esophageal neoplasia (HR 1.78, 95% CI 1.05-3.01)
      was an independent predictor of overall survival. CONCLUSION: This is the first
      report to identify a potential biomarker for predicting second esophageal
      neoplasia in patients with hypopharyngeal carcinoma. In those patients with
      cortactin overexpression and younger age (<=60years old), close surveillance for
      second esophageal neoplasia is required. In addition, the real effect of
      cortactin overexpression on development of primary esophageal carcinoma is
      required to be validated in a large cohort study.

PMID- 30107962
TI  - When a family needs a physician.

PMID- 30107963
TI  - [Exercise capacity in children with mild sleep-disordered breathing].
AB  - INTRODUCTION: While the association between sleep-disordered breathing (SDB) and
      low physical activity has been reported in children, little information is
      available on the impact of SDB on exercise capacity. The aim of this study was to
      assess exercise capacity in children with SDB in order to estimate the relevance
      of exercise training intervention. METHODS: Twelve young patients with suspected
      SDB matched with 11 presumably healthy subjects of same age range (aged 13+/
      0.5yr) were investigated. Both groups underwent physical activity assessment,
      full night polysomnography, incremental and all-out exercise tests. RESULTS: The
      respiratory disturbance index was higher in the patient group (4.6+/-4.7 vs 0.8+/
      0.6; P=0.02). Children with SDB had lower VO2max (32.0+/-9.9 vs 42.3+/-5.7mL.kg
      1.min-1, P=0.007) and lower peak power (8.6+/-3.4 vs 11.8+/-1.9W.kg-1, P=0.009).
      A significant correlation between VO2max and weekly physical activity only was
      found in the SDB group (P=0.005). CONCLUSION: Mild SDB may be associated with
      impairment of both aerobic and anaerobic exercise capacity in children, related
      to poor physical activity. Exercise training could bring clinical benefit in this
      population.

PMID- 30107965
TI  - Pressure-induced stromal keratopathy after laser in situ keratomileusis: Acute
      and late-onset presentations.
AB  - We present a series of 4 cases of pressure-induced stromal keratopathy after
      laser in situ keratomileusis (LASIK). Four patients (5 eyes) with previous LASIK
      presented for poor visual acuity and ocular pain because of ocular hypertension.
      At examination, all cases revealed corneal haze and a space filled with fluid
      between the surgical flap and the residual stroma. All cases were managed with
      topical hypotensive treatment and one of them was also treated with a valve
      drainage device. Topical steroids restriction was indicated in all cases.
      Intraocular pressure (IOP) was normalized in all cases with subsequent interface
      fluid resolution and significant improvement of vision in most cases. Early
      recognition and appropriate treatment for pressure-induced stromal keratopathy is
      essential to avoid complications associated with prolonged elevated IOP. It is
      extremely important to measure the IOP in the peripheral cornea because IOP in
      the central cornea can be incorrectly measured with the characteristic interface
      fluid developed in this entity.

PMID- 30107964
TI  - First metatarsophalangeal joint arthrodesis with two orthogonal two hole plates.
AB  - OBJECTIVE: First MTP joint fusion is a reliable procedure for advanced arthritis
      for the first MTP joint. There are many techniques described. The purpose of our
      study is to report clinical, radiological, functional outcomes and complications
      of first metatarsophalangeal joint fusion with hand preparation of the joint and
      fixation with two orthogonal locking plates without a compression screw. METHODS:
      32 feet in 26 consecutive patients under went first metatarsophalangeal joint
      fusion with above technique. There were 23 women and 3 men. Mean age was 64 years
      and mean follow-up was 49 months. 21 patients had osteoarthritis, 10 had
      rheumatoid arthritis and one had psoriatic arthritis. Clinical, radiological,
      American Orthopaedic Foot and Ankle Score and Foot and Ankle Disability Index
      clinical rating scales were used for evaluation. RESULTS: Fusion was achieved in
      27 feet. The incidence of radiological non-union was 15.7%. Mean AOFAS score
      improved from 37.1 to 80.7 (p < 0.0001) and mean FADI score improved from 40.3 to
      86.9 postoperatively (p < 0.0001). Two patients with osteoarthritis and three
      with Rheumatoid arthritis did not unite. Four of these patients were managing
      hence revision surgery was not carried out but had low AOFAS and FADI scores. One
      patient with symptomatic non-union declined further surgery. One patient needed
      plate removal for a low grade infection and reoperation rate was 3.1%.
      CONCLUSIONS: In our experience, first metatarsophalangeal joint arthrodesis using
      two orthogonal two hole plates without a compression screw is associated with a
      higher non-union rate in our cohort hence we do not recommend this technique.
      LEVEL OF EVIDENCE: Level IV, therapeutic study.

PMID- 30107966
TI  - Diabetes mellitus and hypoglycemia as a complication of intravenous insulin to
      treat hyperkalemia in the emergency department.

PMID- 30107967
TI  - Point-of-care influenza testing does not significantly shorten time to
      disposition among patients with an influenza-like illness.
AB  - INTRODUCTION: Availability of anti-viral agents and need to isolate infected
      patients increases the need to confirm the diagnosis of influenza before
      determining patient disposition. OBJECTIVES: We sought to determine if time-to
      disposition (TTD) was shorter among patients tested for influenza using an
      Emergency Department (ED) Point-of-care (POC) test compared to core laboratory
      (lab) test and to determine difference in antibiotic use between groups. METHODS:
      We prospectively enrolled a convenience sample of ED patients for whom influenza
      testing was ordered during influenza season 2017. Participants were randomized to
      POC or lab. Data collected included demographics, chief complaint, influenza test
      results, turnaround time (TAT), whether antibiotics were given, and TTD.
      Descriptive statistics were calculated and group comparisons conducted using chi
      squared and Wilcoxon Rank Sum tests. RESULTS: Study population included 100 in
      the POC group and 97 in the lab group. Demographics were similar between POC and
      lab participants. More flu positive results were reported in the POC group
      compared to the lab group (51.0% vs. 33.0% p = 0.01). The median TTD was 146.5
      min (IQR 98.5) for POC group and 165.5 min (IQR 127) for lab group (p = 0.26).
      The median TAT was 30.5 min (IQR 7.5) for POC group and 106.0 min (IQR 55) for
      core lab group (p = 0.001). Antibiotics were given to 14.0% of POC participants
      and 14.4% of lab participants (p = 0.93). CONCLUSIONS: Although use of a POC
      influenza test provided more rapid TAT than use of a core lab test, there was no
      significant difference in TTD or antibiotic use between groups.

PMID- 30107968
TI  - National trends in stroke and TIA care in U.S. emergency departments and
      inpatient hospitalizations (2006-2014).
AB  - BACKGROUND: We examine recent trends in U.S. emergency department (ED) and
      hospital care for stroke and transient ischemic attack (TIA). METHOD: We used
      national ED and inpatient data from the Healthcare Cost and Utilization Project
      2006-14. We explored trends in care and outcomes for patients treated in U.S.
      hospitals with stroke and TIA using descriptive statistics, as well as
      intracranial hemorrhage (ICH), a complication of stroke treatment. RESULTS: From
      2006 to 14, there were 3.9 million U.S. ED visits with stroke and 2.5 million
      with TIA. Over the study, stroke visits grew 25% while TIA decreased 2%. Both
      conditions were more common among women and older adults, and most had Medicare
      insurance; however, Medicaid increased from 5.8% to 9.6% for stroke and 4.3% to
      7.5% for TIA. Full inpatient hospitalizations fell for stroke from 89% to 83%,
      and TIA from 61% to 47%. Transfers from the ED for stroke & TIA increased from 4%
      to 8% and 2% to 5%, respectively. Inpatient mortality decreased for stroke & ICH
      and costs increased for all three conditions; however, length of stay (LOS) did
      not significantly change. CONCLUSION: Over this nine-year study period, the
      average age of stroke & TIA patients was unchanged in U.S. hospitals; however,
      the proportion with Medicaid insurance increased considerably. Stroke incidence
      increased while TIA decreased slightly. Full inpatient hospitalizations are
      declining for both conditions, while transfers are on the rise. Average inpatient
      costs increased dramatically for all three conditions while mortality for stroke
      & ICH fell significantly.

PMID- 30107970
TI  - Synthesis and evaluation of 1,2,3,4-tetrahydro-1-acridone analogues as potential
      dual inhibitors for amyloid-beta and tau aggregation.
AB  - Amyloid-beta (Abeta) and tau protein are two crucial hallmarks in Alzheimer's
      disease (AD). Their aggregation forms are thought to be toxic to the neurons in
      the brain. A series of new 1,2,3,4-tetrahydro-1-acridone analogues were designed,
      synthesized, and evaluated as potential dual inhibitors for Abeta and tau
      aggregation. In vitro studies showed that compounds 25-30 (20 MUM) with N
      methylation of the quinolone ring effectively inhibited Abeta1-42 aggregation by
      84.7%-99.5% and tau aggregation by 71.2%-101.8%. Their structure-activity
      relationships are discussed. In particular, 30 could permeate the blood-brain
      barrier, bind to Abeta1-42 and tau, inhibit Abeta1-42 beta-sheets formation, and
      prevent tau aggregation in living cells.

PMID- 30107971
TI  - Ubiquitin, SUMO, and NEDD8: Key Targets of Bacterial Pathogens.
AB  - Manipulation of host protein post-translational modifications (PTMs) is used by
      various pathogens to interfere with host cell functions. Among these
      modifications, ubiquitin (UBI) and ubiquitin-like proteins (UBLs) constitute key
      targets because they are regulators of pathways essential for the host cell. In
      particular, these PTM modifiers control pathways that have been described as
      crucial for infection such as pathogen entry, replication, propagation, or
      detection by the host. Although bacterial pathogens lack eucaryotic-like UBI or
      UBL systems, many of them produce proteins that specifically interfere with these
      host PTMs during infection. In this review we discuss the different mechanisms
      used by bacteria to interfere with host UBI and the two UBLs, SUMO and NEDD8.

PMID- 30107969
TI  - 5-Adamantan thiadiazole-based thiazolidinones as antimicrobial agents. Design,
      synthesis, molecular docking and evaluation.
AB  - In continuation of our efforts to develop new compounds with antimicrobial
      properties we describe design, synthesis, molecular docking study and evaluation
      of antimicrobial activity of seventeen novel 2-{[5-(adamantan-1-yl)-1,3,4
      thiadiazol-2-yl]-imino}-5-arylidene-1,3-thiazolidin-4-ones. All compounds showed
      antibacterial activity against eight Gram positive and Gram negative bacterial
      species. Twelve out of seventeen compounds were more potent than streptomycin and
      all compounds exhibited higher potency than ampicillin. Compounds were also
      tested against three resistant bacterial strains: MRSA, P. aeruginosa and E.
      coli. The best antibacterial potential against ATCC and resistant strains was
      observed for compound 8 (2-{[5-(adamantan-1-yl)-1,3,4-thiadiazol-2-yl]-imino}-5
      (4-nitrobenzylidene)-1,3thiazolidin-4-one). The most sensitive bacterium appeared
      to be S. typhimirium, followed by B. cereus while L. monocitogenes and M. flavus
      were the most resistant. Compounds were also tested for their antifungal activity
      against eight fungal species. All compounds exhibited antifungal activity better
      than the reference drugs bifonazole and ketokonazole (3-115 times). It was found
      that compound 8 appeared again to be the most potent. Molecular docking studies
      on E. coli MurB, MurA as well as C. albicans CYP 51 and dihydrofolate reductase
      were used for the prediction of mechanism of antibacterial and antifungal
      activities confirming the experimental results.

PMID- 30107972
TI  - Relative impact characteristic curve: a graphical tool to visualize and quantify
      the clinical utility and population-level consequences of implementing markers.
AB  - PURPOSE: Receiver operating characteristic (ROC) curve analysis is a popular
      method for evaluating the performance of (bio)markers. However, the standard ROC
      curve does not directly connect marker performance to patient-related outcomes.
      Our aim was to fill this gap by proposing a conceptually similar graphical tool
      that carries information about the clinical uitility of markers. METHODS: We
      propose a novel graphical tool, the relative impact characteristic (RIC) curve,
      that depicts the trade-off between the population-level impact of treatment as a
      function of the size of the treated population for a given marker positivity rule
      (e.g., a threshold). We establish analogies between the ROC and the RIC curves
      around the interpretations of shape, slopes, and area under the curve and discuss
      parametric inference on RIC. RESULTS: As a case study, we used data from a
      clinical trial on preventive therapy for exacerbations of chronic obstructive
      pulmonary disease. We illustrate how the RIC curve can be constructed for a
      predication score and be interpreted in terms of a marker's ability toward
      concentrating treatment benefit in the population. We discuss hoe the RIC curve
      can be used to identify a threshold on the risk score based on the maximal
      acceptable number-needed-to-treat. CONCLUSIONS: The RIC curve enables evaluation
      of markers in terms of their treatment-related clinical utility. Its analogies
      with the standard ROC analysis can facilitate its interpretation, bringing a
      population-based perspective to the activities of diverse marker development and
      evaluation teams.

PMID- 30107974
TI  - Pilot Study of the Effects of High-Protein Meals During Hemodialysis on
      Intradialytic Hypotension in Patients Undergoing Maintenance Hemodialysis.
AB  - OBJECTIVE: Patients undergoing hemodialysis (HD) have high protein and energy
      requirements, and protein-energy wasting is common and associated with poor
      outcomes. Eating during dialysis may improve nutritional status by counteracting
      the catabolic effects of HD treatment; but eating during HD may be discouraged
      because of concerns of postprandial hypotension. However, little data are
      available to support this practice. In this study, we hypothesized that high
      protein meals during HD do not lead to symptomatic intradialytic hypotension
      events. DESIGN: A 9-week, nonrandomized, parallel-arm study. SETTING: A single in
      center HD clinic. SUBJECTS: Eighteen patients undergoing HD from 2 shifts
      completed the study. Patients were aged 62 +/- 16 years with dialysis vintage of
      3.4 +/- 2.6 years. INTERVENTION: Patients in the intervention group (n = 9)
      undergoing HD received meals of ~30 g protein and ~1/3 daily recommended intakes
      of sodium, potassium, phosphorus, and fluid during dialysis for 25 consecutive HD
      sessions. The control group (n = 9) completed all aspects of the study including
      a visit by study personnel but were not given meals. The 25 consecutive sessions
      before the start of the intervention/control phase were used as a baseline
      comparison for each patient. MAIN OUTCOME MEASURE: Symptomatic hypotension event
      frequency. RESULTS: In the intervention arm, there were 19 symptomatic
      hypotension events in 5 patients prestudy and 18 events in 6 patients during the
      study. In the control arm, there were 16 events in 7 patients prestudy and 13
      events in 7 patients during the study. Change in the frequency of symptomatic
      hypotension events from prestudy to during study was not different between groups
      (P = .71). There was no effect of meals on nutritional status, but patients
      reported positive attitudes toward receiving meals during dialysis. CONCLUSION:
      High-protein meals during HD did not increase symptomatic hypotension events.
      Larger, longer term studies are needed to confirm these results and evaluate
      whether high-protein meals on dialysis benefit nutritional status and clinical
      outcomes.

PMID- 30107975
TI  - Traumatic Anterior Dislocation of the Lens.

PMID- 30107976
TI  - StemBell therapy stabilizes atherosclerotic plaques after myocardial infarction.
AB  - BACKGROUND AIMS: After a myocardial infarction (MI) atherosclerosis is
      accelerated leading to destabilization of the atherosclerotic plaque. mesenchymal
      stromal cells are a promising therapeutic option for atherosclerosis. Previously,
      we demonstrated a novel stem cell delivery technique, with adipose stem cells
      coupled to microbubbles (i.e., StemBells) as therapy after MI. In this study, we
      aim to investigate the effect of StemBell therapy on atherosclerotic plaques in
      an atherosclerotic mouse model after MI. METHODS: MI was induced in
      atherosclerotic Apolipoprotein E-deficient mice that were fed a high-fat Western
      diet. Six days post-MI, the mice received either 5 * 105/100 uL StemBells or
      vehicle intravenously. The effects of StemBell treatment on the size and
      stability of aortic root atherosclerotic plaques and the infarcted heart were
      determined 28 days post-MI via (immuno)histological analyses. Moreover, monocyte
      subtypes and lipids in the blood were studied. RESULTS: StemBell treatment
      resulted in significantly increased cap thickness, decreased intra-plaque
      macrophage density and increased percentage of intra-plaque anti-inflammatory
      macrophages and chemokines, without affecting plaque size and serum
      cholesterol/triglycerides. Furthermore, StemBell treatment significantly
      increased the percentage of anti-inflammatory macrophages within the infarcted
      myocardium but did not affect cardiac function nor infarct size. Finally, also
      the average percentage of anti-inflammatory monocytes in the circulation was
      increased after StemBell therapy. DISCUSSION: StemBell therapy increased cap
      thickness and decreased intra-plaque inflammation after MI, indicative of
      stabilized atherosclerotic plaque. It also induced a shift of circulating
      monocytes and intra-plaque and intra-cardiac macrophages towards anti
      inflammatory phenotypes. Hence, StemBell therapy may be a therapeutic option to
      prevent atherosclerosis acceleration after MI.

PMID- 30107977
TI  - Current and Former Smokers: Who Wants To Be Screened?
AB  - BACKGROUND: Lung cancer (LC) screening (LCS) with annual low-dose computed
      tomography scans has been seen to reduce the specific and overall mortality in
      selected populations. However, participation is key to successful screening
      programs. The EDIFICE (etude sur le depistage des cancers et ses facteurs de
      compliance [survey on cancer screening and compliance factors]) nationwide
      observational surveys are used to assess behavior related to cancer screening
      programs in France. MATERIALS AND METHODS: Using comprehensive multivariate
      stepwise logistic regression analyses of data from current and former cigarette
      smokers, we sought to identify the explanatory factors associated with the
      intention to participate in an LCS program. RESULTS: Of the 1463 respondents with
      no personal history of cancer, 263 (36.4%) of the current cigarette smokers and
      170 (26.3%) of the former cigarette smokers stated their willingness to
      participate in an LCS program. The explanatory factors differed between current
      cigarette smokers (already screened for LC: odds ratio [OR], 2.81; < 30 pack
      years: OR, 2.69; intention to quit smoking: OR, 1.96; no social vulnerability:
      OR, 2.15) and former cigarette smokers (comorbidities: OR, 0.31). The usual
      eligibility criteria were not significantly explanatory. CONCLUSION: Our findings
      highlight the discrepancy that exists between target populations and individuals
      who actually intend to participate in a screening program for LC, with subsequent
      potential effects on the participation rates and, thus, on the efficacy of
      screening.

PMID- 30107978
TI  - Classification of patients with septic shock: Are we there yet?

PMID- 30107979
TI  - Response to letter to the editor noninvasive and invasive ventilation in severe
      pneumonia: Insight for the noninvasive ventilator approach.

PMID- 30107980
TI  - Translating EBP Into the Reality of Daily Practice: Leadership Solutions for
      Creating a Path Forward.

PMID- 30107981
TI  - Cochrane Review Summary: Epidural Pain Relief Versus Systemic Opioid-Based Pain
      Relief for Abdominal Aortic Surgery.

PMID- 30107983
TI  - The current and future role of plasma-derived clotting factor concentrate in the
      treatment of haemophilia A.
AB  - While recent advances in recombinant DNA technology, gene therapy and the
      discovery of novel non-substitutional agents have revolutionised the management
      of haemophilia A, plasma-derived clotting factor concentrates continue to be used
      and are likely to remain an important therapeutic option for the foreseeable
      future. The administration of plasma-derived products is associated with a risk
      of pathogen transmission. However, this risk has been greatly reduced, if not
      virtually eliminated, by modern manufacturing techniques. Moreover, FVIII
      inhibitor formation (which has overtaken pathogen transmission as the major
      modern complication of factor replacement therapy) may occur less frequently with
      the use of plasma-derived FVIII concentrates relative to recombinant
      alternatives, although this remains a source of considerable debate. In addition,
      plasma-derived FVIII concentrates remain the primary replacement therapy for
      haemophilia A in the developing world, where access to recombinant therapy is
      more limited. The future role of plasma-derived concentrates globally will be
      determined by several factors including the ability of manufacturers to continue
      to provide safe and affordable product, the potential for plasma-derived
      concentrates to confer lower a risk of inhibitor formation in previously
      untreated patients with haemophilia and the impact of novel therapies on the
      market for plasma-derived products both in the developed and developing world.

PMID- 30107982
TI  - Ultrasound-guided, open-source microneurography: Approaches to improve recordings
      from peripheral nerves in man.
AB  - OBJECTIVE: Microneurography is the only method for recording from single neurons
      in intact human nerves. It is challenging - requiring technical expertise,
      investment in specialised equipment and has sparse data yields. METHODS: We
      assessed whether ultrasound guidance in combination with an 'open access'
      amplifier and data capture system (Open-Ephys) would simplify and expand the
      scope of microneurographic recordings in humans. RESULTS: In 32 healthy
      consenting volunteers, ultrasound-guidance improved success rates for obtaining
      cutaneous C-fibres and reduced "Skin to Nerve" times from 28.5 min to 4.5 min for
      recordings of the peroneal nerve (P < 0.0001). We illustrate the potential
      utility of ultrasound-guided microneurography for difficult to access nerves with
      phrenic nerve recording during a Valsalva manoeuvre. We show that Open Ephys is a
      viable alternative to commercially available recording systems and offers
      advantages in terms of cost and software customisability. CONCLUSIONS: Ultrasound
      guidance for microneurography with Open Ephys facilitates cutaneous C nociceptor
      recordings and allows recordings to be made from nerves previously considered
      inaccessible. SIGNIFICANCE: We anticipate that the adoption of these techniques
      will improve microneurography experimental efficiency, adds an important visual
      learning aid and increases the generalisability of the approach.

PMID- 30107985
TI  - Localizing and lateralizing values of postictal behavioral impairments in
      epileptic rats.
AB  - Transient postictal behavioral impairments in patients with epilepsy provide
      clues to seizure localization, but no attempt has been made previously to study
      the localization/lateralization value of postseizure motor disturbances in
      experimental models of epilepsy. The present study investigated relation of
      postictal motor deficit to seizure localization in the rat model of sound-induced
      reflex epilepsy. Sound-induced motor seizures started with a focal brainstem
      seizure (running) and progressed to a secondarily generalized seizure. Depending
      on innate or acquired seizure susceptibility of rats, focal brainstem seizures
      secondarily generalized within the brainstem (brainstem-generalized seizures) or
      spread to the forebrain (focal or generalized forebrain seizures). All sound
      induced seizures were followed by catalepsy and abnormal limb posturing. The
      duration of the postictal catalepsy and the pattern of the posture abnormality
      depended on brainstem or forebrain localization of secondarily generalized
      seizures. Brainstem-driven seizures induced long-lasting whole-body catalepsy and
      cataleptic limb posture in the postictal period. Secondary seizure generalization
      to the forebrain led to shortening postictal catalepsy and development of rigid
      limb posturing. Asymmetric limb posturing was always observed after focal
      forebrain seizures, and the postictal asymmetry was closely linked to ictal
      asymmetry of the earliest running seizure phase, predicting lateralization of the
      seizure-onset side. This is the first demonstration of circuit-specific postictal
      behavioral impairments and their localization and lateralization values in
      epileptic rats.

PMID- 30107984
TI  - Efficacy of depth jumps to elicit a post-activation performance enhancement in
      junior endurance runners.
AB  - OBJECTIVES: To determine the effect of performing depth jumps (DJ) pre-exercise
      on running economy (RE) and time to exhaustion (TTE) at the speed associated with
      maximal oxygen uptake (sVO2max) in a group of high-performing junior middle
      distance runners. DESIGN: Randomized crossover study. METHODS: Seventeen national
      and international-standard male distance runners (17.6+/-1.2years, 63.4+/-6.3kg,
      1.76+/-0.06m, 70.7+/-5.2mLkg-1min-1) completed two trials. Following a 5min warm
      up at 60% VO2max, participants performed a 5min run at 20%Delta below oxygen
      uptake corresponding with lactate turn-point to determine pre-intervention RE.
      Participants then completed either six DJ from a box equivalent to their best
      counter-movement jump (CMJ) or a control condition (C) involving body weight
      quarter squats. After a 10min passive recovery, another 5min sub-maximal run was
      performed followed by a run to exhaustion at sVO2max. RESULTS: Compared to the C
      trial, DJ produced moderate improvements (-3.7%, 95% confidence interval for
      effect size: 0.25-1.09) in RE, which within the context of minimal detectable
      change is considered possibly beneficial. Differences in TTE and other
      physiological variables were most likely trivial (ES: <0.2). Individual responses
      were small, however a partial correlation revealed a moderate relationship (r=
      0.55, p=0.028) between change in RE and CMJ height. CONCLUSIONS: The inclusion of
      a set of six DJ in the warm-up routine of a well-trained young male middle
      distance runner is likely to provide a moderate improvement in RE.

PMID- 30107986
TI  - Follow-up after surgical treatment in older patients with colorectal cancer: The
      evaluation of emerging health problems and quality of life after implementation
      of a standardized shared-care model.
AB  - INTRODUCTION: One-year mortality after hospital discharge is higher among older
      patients with colorectal cancer who underwent surgery compared to younger
      patients. Taking care of older adults with multi-morbidity is often fragmented
      with lack of coordination and information exchange between healthcare
      professionals. The aim of this study was to evaluate emerging health problems and
      quality of life after implementing a standardized shared-care model. MATERIAL AND
      METHODS: 141 patients aged >=70 years who underwent surgery for colorectal
      carcinoma in two hospitals were included. A standardized transmission from
      hospital to primary care was set up. Patients' health status and quality of life
      was evaluated during subsequent follow-up moments. RESULTS: A reduction in one
      year mortality rate from 10.9% to 9.2% was observed after implementation of the
      standardized shared-care model. Almost all health status domains improved to
      'good' during follow-up moments, still the general condition remained poor in 26%
      of patients at week fourteen. Although quality of life improved during subsequent
      follow-up moments, fatigue, dyspnoea and insomnia were the most prominent
      persisting problems at the end of follow-up. DISCUSSION: The implementation of a
      standardized shared-care model for older patients after surgery for colorectal
      cancer resulted in a reduction in the one year mortality rate. Although most
      aspects of both health status and quality of life improved during subsequent
      follow-up moments, especially the general condition remained poor for a long time
      after surgery. This means that, besides a good preoperative counseling of
      patients, future research should focus on possible interventions to improve
      general condition.

PMID- 30107987
TI  - Onychomycosis: Which fungal species are involved? Experience of the Laboratory of
      Parasitology-Mycology of the Rabta Hospital of Tunis.
AB  - Onychomycosis is a fungal infection of nails caused by dermatophytes, yeasts or
      non-dermatophyte molds. The aim of our study was to describe the epidemiological
      features of onychomycoses encountered in the Tunis region. A retrospective study
      concerned 3458 cases of onychomycosis, confirmed by direct examination and/or a
      positive culture, was conducted in Parasitology - Mycology Laboratory, Rabta
      hospital, over a five-year period (2012-2016). Our patients were aged 1 to 85;
      more than half of the patients were aged over 60 years with a female predominance
      (67%). Toenail infections were most common, observed in 2702 cases (78%). Direct
      examination was positive in 3284 cases (95%), culture in 2409 cases (69.6%);
      these two examinations were positive simultaneously in 2235 cases (64.6%). The
      causative agents of these onychomycoses were dominated by the genus Candida in
      fingernails: Candida albicans (55.6%), Candida tropicalis (8.5%) and Candida
      parapsilosis (8.2%) were the most frequently incriminated species; while in
      toenail lesions, Trichophyton rubrum was by far the most frequently isolated
      species (96.8%). Our results join the literature; onychomycosis is a pathology of
      the adult, mainly candidosic etiology in hands and dermatophytic in feet.

PMID- 30107988
TI  - Evaluation of the effect of TIM-3 suppression by miR-498 and its effect on
      apoptosis and proliferation rate of HL-60 cell line.
AB  - BACKGROUND: Acute Myeloid Leukemia (AML) is a Cancer of hematopoietic stem cells
      with a rapid progression. TIM-3 is expressed on leukemic stem cells (LSCs) in
      most types of AML and might have a positive effect on maintenance of malignant
      phenotype. MicroRNAs play important roles in either cancer progression or
      suppression. In this study were evaluated, the inhibitory effect of miR-498 on
      TIM-3 expression and its impact on proliferation and survival of HL-60 cell line.
      METHODS: Firstly, the probable inhibitory effect of miR-498 on TIM-3 expression
      was predicted. HL-60 cells were cultured and expression of TIM-3 was induced on
      the cells using phorbol miristate acetate. The cells were transfected with miR
      498 and expression level of TIM-3 were measured using with q-RT-PCR and flow
      cytometry methods. In addition, the effect of suppression of TIM-3 expression in
      HL-60 cell line was analyzed with apoptosis and cell proliferation assays.
      RESULTS: Bioinformatics analyses predicted that miR-498 has high ability to
      silence TIM-3 gene expression. Our experiments confirmed that miR-498 was able to
      strongly silence TIM-3 expression (68% silencing) in HL-60 cell line (P < 0.002).
      Also, the cells with suppressed expression of TIM-3 had a lower proliferation and
      higher apoptosis rates. CONCLUSION: Based on our results, the miR-498 can
      effectively suppress TIM-3 expression in the AML cell line. TIM-3 suppression, in
      turn, inhibits malignant cell proliferation and induces its apoptosis.
      Collectively, suppression of TIM-3 by miR-498 can be considered as a potential
      powerful way for treatment of AML.

PMID- 30107989
TI  - Small nucleolar RNA host gene 1: A new biomarker and therapeutic target for
      cancers.
AB  - OBJECTIVES: Long non-coding RNAs (lncRNAs), a group of transcripts with length
      greater than 200 nucleotides, have been involved in multiple pathophysiological
      processes of the human body, especially in tumorigenesis and progression of
      cancers. The aberrant expression of lncRNAs processes crucial functions involved
      in proliferation, apoptosis and metastatic capacity of cancers. Recent studies
      have revealed that small nucleolar RNA host gene 1 (SNHG1), a long non-coding RNA
      transcribed from UHG, was located in chromosome 11. Aberrant expression of SNHG1
      has been demonstrated to be associated with various sites of cancers such as
      glioma, esophageal cancer, gastric cancer and many others, and its deregulation
      could be related to survival and prognosis of cancer patients. Pertinent to
      clinical practice, SNHG1 might act as a prognostic biomarker for tumors and might
      even serve as potential target for therapy. In this review, we summarized current
      researches concerning the role of SNHG1 in tumor progression and discussed its
      mechanisms involved. MATERIALS AND METHODS: In this review, we summarized and
      figured out recent studies concerning the expression and biological mechanisms of
      SNHG1in tumor development. The related studies were obtained through a systematic
      search of PubMed, Embase and Cochrane Library. RESULTS: SNHG1 was a valuable
      cancer-related lncRNA that the expression level was up-regulation in a variety of
      malignancies, including glioma, esophageal cancer, lung cancer, gastric cancer,
      hepatocellular carcinoma, colorectal carcinoma, prostate cancer, cervical cancer,
      osteosarcoma, neuroblastoma, nasopharyngeal carcinoma. The aberrant expressions
      of SNHG1 have shown to contribute to proliferation, migration, and invasion of
      cancer cells. CONCLUSIONS: SNHG1 represents promising novel biomarkers for
      various cancer types and have a great potential to be effectively used in
      clinical practice in the near future.

PMID- 30107990
TI  - LncRNA UCA1 sponges miR-204-5p to promote migration, invasion and epithelial
      mesenchymal transition of glioma cells via upregulation of ZEB1.
AB  - Long non-coding RNA urothelial carcinoma associated 1 (lncRNA UCA1) promotes
      cancer progression and enhances chemoresistance through miR-204-5p in a few
      cancers. However, no studies have investigated whether UCA1 regulates glioma
      metastasis through miR-204-5p and its target. In the present study, cell
      migration, invasion and epithelial-mesenchymal transition (EMT) were evaluated in
      glioma cells overexpressing UCA1. The relationships among UCA1, miR-204-5p and
      ZEB1 were examined by real-time PCR, western blotting and dual-luciferase
      reporter assays. The effect of UCA1 knockdown on xenograft tumor growth was
      investigated. The levels of miR-204-5p, fibronectin, COL5 A1 and ZEB1 in tumor
      tissues were also determined. The results showed that UCA1 overexpression
      promoted cell migration, invasion and EMT. UCA1 interacted with miR-204-5p and
      decreased its level. ZEB1 was identified as a direct target of miR-204-5p and miR
      204-5p negatively regulated ZEB1 expression. Moreover, UCA1 sponged miR-204-5p
      and partially rescued the inhibitory effect of miR-204-5p on ZEB1. In our in vivo
      studies, UCA1 knockdown reduced tumor volume and tumor weight. In addition, the
      levels of fibronectin, COL5 A1 and ZEB1 were decreased, while miR-204-5p level
      was increased. The present study provides the first evidence that UCA1 promotes
      glioma metastasis through the miR-204-5p/ZEB1 axis, contributing to the
      understanding of the pathogenesis of glioma.

PMID- 30107991
TI  - Rabies vaccines: WHO position paper, April 2018 - Recommendations.
AB  - This article presented the World Health Organization's (WHO) recommendations on
      the use of Rabies vaccines excerpted from the Rabies vaccines: WHO position paper
      - April 2018 published in the Weekly Epidemiological Record [1] This position
      paper replaces the 2010 WHO position paper on rabies vaccines [2]. It presents
      new evidence in the field of rabies and the use of rabies vaccines, focussing on
      programmatic feasibility, simplification of vaccination schedules and improved
      cost-effectiveness. The recommendations concern the 2 main immunization
      strategies, namely vaccination for post-exposure prophylaxis and vaccination for
      pre-exposure prophylaxis. In the context of post-exposure prophylaxis,
      recommendations are also provided on the use of rabies immunoglobulins. Footnotes
      to this paper provide a number of core references including references to grading
      tables that assess the quality of the scientific evidence, and to the evidence-to
      recommendation tables. In accordance with its mandate to provide guidance to
      Member States on health policy matters, WHO issues a series of regularly updated
      position papers on vaccines and combinations of vaccines against diseases that
      have an international public health impact. These papers are concerned primarily
      with the use of vaccines in large-scale immunization programmes; they summarize
      essential background information on diseases and vaccines, and conclude with
      WHO's current position on the use of vaccines in the global context.
      Recommendations on the use of cholera vaccines were discussed by the Strategic
      Advisory Group of Experts (SAGE) in October 2017; evidence presented at these
      meetings can be accessed at:
      http://www.who.int/immunization/sage/meetings/2017/october/presentations_backgrou
      d_docs/en/.

PMID- 30107992
TI  - Rubella virus neutralizing antibody response after a third dose of measles-mumps
      rubella vaccine in young adults.
AB  - BACKGROUND: Third doses of measles-mumps-rubella (MMR) vaccine have been
      administered during mumps outbreaks and in various non-outbreak settings. The
      immunogenicity of the rubella component has not been evaluated following receipt
      of a third dose of MMR vaccine. METHODS: Young adults aged 18-31 years with
      documented two doses of MMR vaccine received a third dose of MMR vaccine between
      July 2009 and October 2010. Rubella neutralizing antibody titers were assessed
      before, 1 month, and 1 year after receipt of a third dose of MMR vaccine.
      RESULTS: Among 679 participants, 1.8% had rubella antibody titers less than 10
      U/ml, immediately before vaccination, approximately 15 years after receipt of a
      second dose of MMR vaccine. One month after receipt of a third dose of MMR
      vaccine, average titers were 4.5 times higher and >50% of participants had a 4
      fold boost. Response was highest among those with titers less than 10 U/ml prior
      to vaccination (geometric mean titer ratio = 18.8; 92% seroconversion) and
      decreased with increasing pre-vaccination titers. Average titers declined 1 year
      postvaccination but remained significantly higher than pre-vaccination levels.
      The proportion classified as low-positive antibody levels increased from 3% 1
      month postvaccination to 24% 1 year postvaccination. CONCLUSIONS: Vaccination
      with a third dose of MMR vaccine resulted in a robust boosting of rubella
      neutralizing antibody response that remained elevated 1 year later. Young adults
      with low rubella titers are more likely to benefit from a third dose of MMR
      vaccine.

PMID- 30107993
TI  - Immunogenicity and protective efficacy of monovalent PCVs containing 22F and 33F
      polysaccharides in mouse models of colonization and co-infection.
AB  - BACKGROUND: In the current transmission, we studied the immunogenicity and
      protective efficacy of serotypes 22F and 33F in the prevention of colonization
      and of invasive Streptococcus pneumoniae (Spn) pathogenesis during an influenza
      co-infection. Serotypes 22F and 33F are emerging Spn serotypes, which are not
      part of currently administered pneumococcal conjugate vaccine formulations
      (PCVs). Spn serotype 6A is an ingredient in the currently administered PCV13
      vaccine and was therefore included in the study as a control. METHODS: Adult (six
      weeks) and infant (two weeks) C57BL/6 mice were intranasally infected in the
      nasopharynx (NP) with Spn serotypes 22F, 33F, or 6A. Influenza A H1N1 A/Puerto
      Rico/8/193 virus (PR8) was introduced one day after the NP Spn colonization. In
      an immunization challenge study, mice were vaccinated with monovalent 22F, 33F,
      or 6A polysaccharide conjugated to the CRM197 antigen. The immunized mice were
      colonized or co-infected to study the vaccines efficacy. RESULTS: All three Spn
      serotypes established colonization in adult and infant mice. The co-infected mice
      showed an increase in Spn NP density. Invasive Spn infection (bacteremia) was
      observed following the co-infection with serotypes 22F and 6A but not 33F in
      adult mice, whereas infant mice developed bacteremia following co-infection with
      all three Spn serotypes. The vaccinations led to robust serum antibody responses
      to capsular polysaccharides 22F, 6A, and less for 33F. The vaccinations resulted
      in reductions of Spn NP colonization density for all three serotypes, prevention
      of bacteremia, and increased survival with Spn serotypes 22F and 6A. Passive
      transfer of antisera was associated with a reduction of Spn colonization
      densities in infant mice. CONCLUSION: Vaccinations with monovalent 22F, 33F, or
      6A formulations protect against Spn colonization, and the efficacy of the 22F
      vaccination was comparable to the 6A vaccination in preventing an invasive Spn
      bacterial infection during an influenza co-infection.

PMID- 30107995
TI  - School entry vaccination requirement program: Experience from the Republic of
      Korea.

PMID- 30107994
TI  - An intrinsic fluorescence method for the determination of protein concentration
      in vaccines containing aluminum salt adjuvants.
AB  - Determination of protein concentration in vaccines containing aluminum salt
      adjuvant typically necessitates desorption of the protein prior to analysis. Here
      we describe a method based on the intrinsic fluorescence of tyrosine and
      tryptophan that requires no desorption of proteins. Adjuvanted formulations of
      three model Bordetella pertussis antigens were excited at 280 nm and their
      emission spectra collected from 290 to 400 nm. Emission spectra of protein
      antigens in the presence of aluminum salt adjuvants were able to be detected, the
      effects of adjuvants on the spectra were analyzed, and linear regressions were
      calculated. The fluorescence method proved to be very sensitive with a limit of
      quantification between 0.4 and 4.4 ug/mL and limit of linearity between 100 and
      200 ug/mL, across the formulations tested. The fluorescence method was found to
      be influenced by adjuvant presence, type of adjuvant, adjuvant concentration,
      buffer and pH conditions. The method also demonstrated ability to monitor the
      percent adsorption of antigens to the adjuvants. Furthermore, intrinsic
      fluorescence showed good correlation with micro-Kjeldahl elemental assay in
      quantifying protein concentration. Being a non-invasive, quick and sensitive
      method, intrinsic fluorescence has the potential to be utilized as a high
      throughput tool for vaccine development and conceivably implemented in-line,
      using in-line fluorimeters, to monitor antigen concentration during formulation
      processing.

PMID- 30107996
TI  - Virus-like particle vaccines expressing Toxoplasma gondii rhoptry protein 18 and
      microneme protein 8 provide enhanced protection.
AB  - Toxoplasma gondii rhoptry protein 18 (ROP18) and microneme protein 8 (MIC8) are
      important invasion factors that mediate parasite multiplication. The main
      objective of this study was to determine the immunogenicity and efficacy by virus
      like particle (VLP) vaccines of T. gondii ROP18 VLPs and MIC8 VLPs in combination
      or individuals. Mice were intranasally immunized with single ROP18 VLPs or MIC8
      VLPs, or a combination of ROP18 VLPs and MIC8 VLPs followed by challenge with T.
      gondii tachyzoites (GT1) through intraperitoneal injection or challenge with T.
      gondii (ME49) through oral infection. Vaccination with a combination of ROP18
      VLPs and MIC8 VLPs resulted in more potent effects on inducing parasite
      neutralizing activity, memory T cell response, and reducing parasite burden
      compared to single VLP vaccination. Lower levels of inflammatory cytokines (IFN
      gamma, IL-6) and apoptosis responses were observed with VLP vaccine combination
      after challenge. These results suggest that VLP vaccines presenting both T.
      gondii ROP18 and MIC8 antigens confer enhanced protection compared to a single
      VLPs vaccine, and VLP platforms could be developed as potential vaccines against
      toxoplasmosis.

PMID- 30107998
TI  - Breaking and Sealing Barriers in Retinal Gene Therapy.

PMID- 30107999
TI  - Unique Challenges of Hepatitis C in Infants, Children, and Adolescents.
AB  - PURPOSE: Hepatitis C, a chronic disease with deadly consequences, is no longer
      predominantly a disease of older people. METHODS: A limited search was conducted
      of the relevant literature on 2 topics: (1) the impact of hepatitis C on infants
      exposed by vertical transmission; and (2) the impact of hepatitis C infection on
      infected children and adolescents. The findings were supplemented by the first
      hand experience of the authors. FINDINGS: Young people, including women of
      childbearing age, infants, children, and adolescents, are being especially
      affected by hepatitis C infection secondary to the intravenous drug use and
      opioid epidemic. Unfortunately, estimates of disease in young populations are all
      misleading because universal screening has not been implemented. IMPLICATIONS:
      Lack of implementation of policies for screening and therapy on most affected
      populations will be responsible for perpetuation of this infection. In the era of
      highly effective therapy and a regimen that is approved by the US Food and Drug
      Administration for children, this outcome is unacceptable.

PMID- 30108000
TI  - Fenfluramine: Back From the Dead.

PMID- 30108001
TI  - Discrepancies Between US Food and Drug Administration Vaccine Licensure
      Indications and Advisory Committee on Immunization Practices Recommendations:
      Provider Knowledge and Attitudes.
AB  - PURPOSE: In the United States, the Center for Biologics Evaluation and Research
      at the US Food and Drug Administration (FDA) is responsible for licensure of
      vaccines. The Advisory Committee on Immunization Practices (ACIP) is a federal
      advisory committee that provides guidance to the Centers for Disease Control and
      Prevention (CDC) on use of vaccines. Discrepancies between FDA licensure
      indications and ACIP/CDC vaccine recommendations exist, challenging health care
      providers. The objectives of this study were: (1) to categorize differences
      between FDA vaccine licensure indications and ACIP/CDC vaccine recommendations
      for vaccines; and (2) to assess knowledge, attitudes, and practices of
      pediatricians, family physicians, and obstetrician-gynecologists regarding their
      understanding of differences. METHODS: Information was extracted from FDAvaccine
      package inserts, and corresponding information was collected for ACIP/CDC vaccine
      recommendations (2000-2014) for vaccines in the childhood and adult immunization
      schedules. Surveys regarding knowledge of discrepancies were distributed
      electronically to members of the Georgia chapters of the American Academy of
      Pediatrics (GA-AAP) and the American Academy of Family Physicians (GA-AAFP), and
      the national American College of Obstetricians and Gynecologists (ACOG) in 2014.
      FINDINGS: Differences were identified in 20 instances: differences in age group
      indications were identified in 6, in dosing administration schedules in 4, and in
      immunocompromised hosts and pregnant women in 10. We received 145 (8.5%)
      responses from GA-AAP, 237 (9.5%) from GA-AAFP, and 869 (1.5%) from national ACOG
      members. A total of 105 (72%) GA-AAP respondents reported that they follow AAP
      recommendations and 168 (71%) GA-AAFP respondents follow ACIP recommendations. GA
      AAP and GA-AAFP respondents generally were not aware of data the FDA considers
      for vaccine licensure or data that pharmaceutical company representatives are
      permitted to discuss. Respondents remain current with vaccine recommendations
      through review of materials from professional organizations, the CDC, and package
      inserts; Continuing Medical Education; and information from pharmaceutical
      representatives. A total of 780 (90%) ACOG respondents had no concerns regarding
      routinely recommended reduced diphtheria toxoid and acellular pertussis vaccines
      (n = 730 [84%]) and influenza during pregnancy vaccines (n = 852 [98%]) to
      pregnant patients. However, these findings must be interpreted within the context
      of a low overall ACOG survey response rate. IMPLICATIONS: Education regarding
      existence of and reasons for discrepancies between FDA licensure of and ACIP/CDC
      recommendations for vaccines and reasons for these differences could optimize
      immunization delivery.

PMID- 30107997
TI  - It's All in the Delivery: Designing Hydrogels for Cell and Non-viral Gene
      Therapies.
AB  - Hydrogels provide a regenerative medicine platform with their ability to create
      an environment that supports transplanted or endogenous infiltrating cells and
      enables these cells to restore or replace the function of tissues lost to disease
      or trauma. Furthermore, these systems have been employed as delivery vehicles for
      therapeutic genes, which can direct and/or enhance the function of the
      transplanted or endogenous cells. Herein, we review recent advances in the
      development of hydrogels for cell and non-viral gene delivery through
      understanding the design parameters, including both physical and biological
      components, on promoting transgene expression, cell engraftment, and ultimately
      cell function. Furthermore, this review identifies emerging opportunities for
      combining cell and gene delivery approaches to overcome challenges to the field.

PMID- 30108002
TI  - Correlation of Functional Lung Heterogeneity and Dosimetry to Radiation
      Pneumonitis using Perfusion SPECT/CT and FDG PET/CT Imaging.
AB  - PURPOSE: To apply a previously designed framework for predicting radiation
      pneumonitis by using pretreatment lung function heterogeneity metrics, anatomic
      dosimetry, and functional lung dosimetry derived from 2 imaging modalities within
      the same cohort. METHODS AND MATERIALS: Treatment planning computed tomography
      (CT) scans were co-registered with pretreatment [99mTc] macro-aggregated albumin
      perfusion single-photon positron emission tomography (SPECT)/CT scans and [18F]
      fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT scans of 28
      patients who underwent definitive thoracic radiation. Clinical radiation
      pneumonitis was defined as grade >=2 (Common Terminology Criteria for Adverse
      Events, v. 4). Anatomic dosimetric parameters (mean lung dose [MLD], volume
      receiving >=20 Gy [V20]) were collected from treatment planning scans. Baseline
      functional lung heterogeneity parameters and functional lung dose-volume
      parameters were calculated from pretreatment SPECT/CT and FDG PET/CT scans.
      Functional heterogeneity parameters calculated over the tumor-subtracted lung
      included skewness, kurtosis, and coefficient of variation from perfusion SPECT
      and FDG PET and the global lung parenchymal glycolysis and mean standardized
      uptake value from FDG PET. Functional dose-volume parameters calculated in
      regions of highly functional lung, defined on perfusion (p) or SUV (s) images,
      included mean lung dose (pMLD, sMLD) and V20 (pV20, sV20). Fraction of integral
      lung function receiving >=20 Gy (pF20, sF20) was also calculated. Equivalent
      doses in 2 Gy per fraction (EQD2) were calculated to account for differences in
      treatment regimens and dose fractionation (EQD2Lung). RESULTS: Two anatomic
      dosimetric parameters (MLD, V20) and 4 functional dosimetric parameters (pMLD,
      pV20, pF20, sF20) were significant predictors of grade >=2 pneumonitis (area
      under the curve >0.84; P < .05). Dose-independent functional lung heterogeneity
      metrics were not associated with pneumonitis incidence. At thresholds of 100%
      sensitivity and 65% to 91% specificity, corresponding to maximum prediction
      accuracy for pneumonitis, these parameters had the following cutoff values: MLD =
      13.6 Gy EQD2Lung, V20 = 25%, pMLD = 13.2 Gy EQD2Lung, pV20 = 15%, pF20 = 17%, and
      sF20 = 25%. Significant parameters MLD, V20, pF20, and sF20 were not cross
      correlated to significant parameters pMLD and pV20, indicating that they may
      offer independently predictive information (Spearman rho < 0.7). CONCLUSIONS: We
      reported differences in anatomic and functional lung dosimetry between patients
      with and without pneumonitis in this limited patient cohort. Adding selected
      independent functional lung parameters may risk stratify patients for
      pneumonitis. Validation studies are ongoing in a prospective functional lung
      avoidance trial at our institution.

PMID- 30108003
TI  - Clinical Applications of Quantitative 3-Dimensional MRI Analysis for Pediatric
      Embryonal Brain Tumors.
AB  - PURPOSE: To investigate the prognostic utility of quantitative 3-dimensional
      magnetic resonance imaging radiomic analysis for primary pediatric embryonal
      brain tumors. METHODS AND MATERIALS: Thirty-four pediatric patients with
      embryonal brain tumor with concurrent preoperative T1-weighted postcontrast
      (T1PG) and T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic
      resonance images were identified from an institutional database. The median
      follow-up period was 5.2 years. Radiomic features were extracted from axial T1PG
      and FLAIR contours using MATLAB, and 15 features were selected for analysis based
      on qualitative radiographic features with prognostic significance for pediatric
      embryonal brain tumors. Logistic regression, linear regression, receiver
      operating characteristic curves, the Harrell C index, and the Somer D index were
      used to test the relationships between radiomic features and demographic
      variables, as well as clinical outcomes. RESULTS: Pediatric embryonal brain
      tumors in older patients had an increased normalized mean tumor intensity (P =
      .05, T1PG), decreased tumor volume (P = .02, T1PG), and increased markers of
      heterogeneity (P <= .01, T1PG and FLAIR) relative to those in younger patients.
      We identified 10 quantitative radiomic features that delineated medulloblastoma,
      pineoblastoma, and supratentorial primitive neuroectodermal tumor, including size
      and heterogeneity (P <= .05, T1PG and FLAIR). Decreased markers of tumor
      heterogeneity were predictive of neuraxis metastases and trended toward
      significance (P = .1, FLAIR). Tumors with an increased size (area under the curve
      = 0.7, FLAIR) and decreased heterogeneity (area under the curve = 0.7, FLAIR) at
      diagnosis were more likely to recur. CONCLUSIONS: Quantitative radiomic features
      are associated with pediatric embryonal brain tumor patient age, histology,
      neuraxis metastases, and recurrence. These data suggest that quantitative 3
      dimensional magnetic resonance imaging radiomic analysis has the potential to
      identify radiomic risk features for pediatric patients with embryonal brain
      tumors.

PMID- 30108004
TI  - Cognitive and Adaptive Outcomes After Proton Radiation for Pediatric Patients
      With Brain Tumors.
AB  - PURPOSE: Radiation therapy is integral in treatment of pediatric brain tumors,
      but it is associated with negative long-term sequelae. Proton beam radiation
      therapy (PRT), which enables better focusing of radiation on tumors, may entail
      fewer sequelae. This prospective study examined cognitive and adaptive
      functioning in children and young adults treated with PRT. METHODS AND MATERIALS:
      A total of 155 patients were assessed using age-appropriate measures for
      cognitive and adaptive functioning at start of or during PRT (baseline) and at
      follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6
      years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial
      tumors, germ cell tumors, and others. The sample was divided by age at baseline
      (<6 years [N = 57, or 37%] and >=6 years [N = 98, or 63%]) and by PRT field
      (craniospinal irradiation [CSI; 39%] and focal irradiation [61%]). RESULTS:
      Scores for mean intelligence quotient (IQ) and adaptive functioning skills were
      in the average range at baseline and follow-up. Overall, mean IQ scores declined
      from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed
      significant decline. Patients receiving CSI, regardless of age, appeared
      particularly vulnerable in IQ, processing speed, and working memory. Adaptive
      skills were stable across the 4 age-by-treatment field groups. CONCLUSIONS: At a
      mean of 3.6 years after PRT, IQ declined slightly for the group, largely because
      of significant IQ decline in younger patients treated with CSI. No significant
      change was seen in patients <6 years treated with focal PRT or in older patients.
      Adaptive skills remained stable across age and treatment type.

PMID- 30108005
TI  - MR-Only Brain Radiation Therapy: Dosimetric Evaluation of Synthetic CTs Generated
      by a Dilated Convolutional Neural Network.
AB  - PURPOSE: This work aims to facilitate a fast magnetic resonance (MR)-only
      workflow for radiation therapy of intracranial tumors. Here, we evaluate whether
      synthetic computed tomography (sCT) images generated with a dilated convolutional
      neural network (CNN) enable accurate MR-based dose calculations in the brain.
      METHODS AND MATERIALS: We conducted a retrospective study of 52 patients with
      brain tumors who underwent both computed tomography (CT) and MR imaging for
      radiation therapy treatment planning. To generate the sCTs, a T1-weighted
      gradient echo MR sequence was selected from the clinical protocol for multiple
      types of brain tumors. sCTs were created for all 52 patients with a dilated CNN
      using 2-fold cross validation; in each fold, 26 patients were used for training
      and the remaining 26 patients were used for evaluation. For each patient, the
      clinical CT-based treatment plan was recalculated on sCT. We calculated dose
      differences and gamma pass rates between CT- and sCT-based plans inside body and
      planning target volume. Geometric fidelity of the sCT and differences in beam
      depth and equivalent path length were assessed between both treatment plans.
      RESULTS: sCT generation took 1 minute per patient. Over the patient population,
      the mean absolute error of the sCT within the intersection of body contours was
      67 +/- 11 HU (+/-1 standard deviation [SD], range: 51-117 HU), and the mean error
      was 13 +/- 9 HU (+/-1 SD, range: -2 to 38 HU). Dosimetric analysis showed mean
      deviations of 0.00% +/- 0.02% (+/-1 SD, range: -0.05 to 0.03) for dose within the
      body contours and -0.13% +/- 0.39% (+/-1 SD, range: -1.43 to 0.80) inside the
      planning target volume. Mean gamma1mm/1% was 98.8% +/- 2.2% for doses >50% of the
      prescribed dose. CONCLUSIONS: The presented dilated CNN generated sCTs from
      conventional MR images without adding scan time to the acquisition. Dosimetric
      evaluation suggests that dose calculations performed on the sCTs are accurate and
      can therefore be used for MR-only intracranial radiation therapy treatment
      planning.

PMID- 30108007
TI  - Improved effectiveness of the repositionable GORE EXCLUDER AAA endoprosthesis
      featuring the C3 delivery system compared with the original GORE EXCLUDER AAA
      endoprosthesis for within the instructions for use treatment of aortoiliac
      aneurysms.
AB  - OBJECTIVE: To compare two endograft types, the original GORE EXCLUDER AAA
      endoprosthesis (W. L. Gore & Associates, Flagstaff, Ariz) with the repositionable
      GORE EXCLUDER featuring the C3 delivery system, which allows repositioning of the
      proximal part of the graft to achieve accurate placement in relation to the renal
      arteries, in unselected patients with aortoiliac aneurysms. In a second nested,
      substudy we investigated the relative effect of the standard Gore and Gore
      Dryseal introducer sheaths on intraoperative transfusion needs. METHODS: We
      retrospectively analyzed prospectively collected information. The primary
      composite outcome measure was the intraoperative misdeployment or migration of
      the endograft's main body, proximally or distally to the renals (leading to
      technical failure or requiring either placement of aortic cuff extenders or
      conversion to open repair). Secondary outcome measures included the composite
      long-term event of rupture and/or type I/III endoleak. RESULTS: A total of 313
      consecutive patients (303 males; median age, 73 years) had either an original
      GORE EXCLUDER device (n = 174) or the new device (n = 139) placed between 2004
      and 2011 and 2011 and 2017, respectively, to treat an infrarenal aortoiliac
      aneurysm or an isolated common iliac artery aneurysm. The primary composite
      outcome measure occurred more often in patients who had the original GORE
      EXCLUDER device placed (10.9% vs 3.6% for the new device; odds ratio, 0.30; 95%
      confidence interval, 0.11-0.84; P = .016), confirmed by multivariate logistic
      regression analysis. This difference between the two groups was exclusively
      driven by distal misdeployment or migration of the endograft (10.3% vs 2.9% for
      the new device; P = .01), mostly requiring aortic extender placement.
      Intraoperative blood transfusion rates were lower in patients who had the GORE
      Dryseal introducer sheath used (1.1% vs 18.9% for the original GORE introducer
      sheath; OR, 0.05; 95% confidence interval, 0.006-0.35; P < .001). At a mean
      follow-up of 1.7 years (maximum, 13 years), 11 patients developed the composite
      event. On univariate Cox analysis, significant predictors included female gender
      (P = .003), absence of dyslipidemia (P = .023), the primary outcome measure (P =
      .006), and failure to cannulate (P = .009), but not device type or other
      variables. On multivariate Cox regression, female gender (hazard ratio, 37; P <
      .001), chronic obstructive pulmonary disease (hazard ratio, 3.99; P = .045), the
      primary outcome measure of the study (hazard ratio, 8.9; P = .002), and failure
      to cannulate (hazard ratio, 43; P = .003) were all independent predictors.
      CONCLUSIONS: Our study has demonstrated that the repositionable GORE EXCLUDER has
      important safety characteristics compared with the original device and equivalent
      long-term effectiveness. Additional benefit was obtained with the use of the Gore
      Dryseal introducer sheath.

PMID- 30108006
TI  - Modeling Patient-Specific Dose-Function Response for Enhanced Characterization of
      Personalized Functional Damage.
AB  - PURPOSE: Functional-guided radiation therapy (RT) plans have the potential to
      limit damage to normal tissue and reduce toxicity. Although functional imaging
      modalities have continued to improve, a limited understanding of the functional
      response to radiation and its application to personalized therapy has hindered
      clinical implementation. The purpose of this study was to retrospectively model
      the longitudinal, patient-specific dose-function response in non-small cell lung
      cancer patients treated with RT to better characterize the expected functional
      damage in future, unknown patients. METHODS AND MATERIALS: Perfusion single
      photon emission computed tomography/computed tomography scans were obtained at
      baseline (n = 81), midtreatment (n = 74), 3 months post-treatment (n = 51), and 1
      year post-treatment (n = 26) and retrospectively analyzed. Patients were treated
      with conventionally fractionated RT or stereotactic body RT. Normalized perfusion
      single-photon emission computed tomography voxel intensity was used as a
      surrogate for local lung function. A patient-specific logistic model was applied
      to each individual patient's dose-function response to characterize functional
      reduction at each imaging time point. Patient-specific model parameters were
      averaged to create a population-level logistic dose-response model. RESULTS: A
      significant longitudinal decrease in lung function was observed after RT by
      analyzing the voxelwise change in normalized perfusion intensity. Generated dose
      function response models represent the expected voxelwise reduction in function,
      and the associated uncertainty, for an unknown patient receiving conventionally
      fractionated RT or stereotactic body RT. Differential treatment responses based
      on the functional status of the voxel at baseline suggest that initially higher
      functioning voxels are damaged at a higher rate than lower functioning voxels.
      CONCLUSIONS: This study modeled the patient-specific dose-function response in
      patients with non-small cell lung cancer during and after radiation treatment.
      The generated population-level dose-function response models were derived from
      individual patient assessment and have the potential to inform functional-guided
      treatment plans regarding the expected functional lung damage. This type of
      patient-specific modeling approach can be applied broadly to other functional
      response analyses to better capture intrapatient dependencies and characterize
      personalized functional damage.

PMID- 30108008
TI  - Optimal medical management before lower extremity bypass for claudication in the
      veteran population.
AB  - OBJECTIVE: Optimizing medical management through glucose control, smoking
      cessation, and drug therapy (ie, antiplatelet and statin agents) is recommended
      as first-line therapy for patients with claudication. The aims of this study were
      to determine how frequently veterans with claudication received optimal medical
      management (OMM) before undergoing elective open lower extremity bypass
      procedures nationwide and whether preoperative OMM was associated with improved
      surgical outcomes. METHODS: We reviewed all patients within the Veterans Affairs
      (VA) Surgical Quality Improvement Program database who underwent elective open
      lower extremity bypass procedures for claudication at nationwide VA medical
      centers from 2005 until 2015. We defined OMM as a claudicant's having
      documentation of receiving all of the following within 12 months before surgery:
      prescriptions for antiplatelet, statin, and smoking cessation therapy (if a
      smoker) and monitoring of hemoglobin A1c (if diabetic). Outcome measures included
      occurrence of any 30-day VA Surgical Quality Improvement Program complication,
      amputation-free survival, and 30-day and 1-year mortality. We used multivariate
      regression and Cox proportional hazards models incorporating inverse probability
      treatment weighting to analyze the effect of OMM on outcome measures after
      adjusting for patient-level confounding. RESULTS: Among 10,271 lower extremity
      bypass procedures performed, 2265 (22%) were undertaken in claudicants with a
      median age of 63 years (interquartile range, 58-68 years). Of claudicants, 839
      (37%) were diabetic, and 1333 (59%) patients smoked within 12 months before
      surgery. OMM was achieved in only 581 (26%) claudicants before they underwent
      surgery, although adherence to individual components was variable: antiplatelet,
      55%; statin, 63%; smoking cessation, 58%; and hemoglobin A1c monitoring, 92%. In
      risk-adjusted analyses, there were no statistically significant differences in
      complication rates, amputation-free survival, or mortality outcomes among
      patients who received OMM compared with non-OMM patients. CONCLUSIONS: Only a
      quarter of veterans with claudication were documented as receiving OMM within the
      year before undergoing open lower extremity bypass across nationwide VA medical
      centers, highlighting the need for strategies to ensure that medical therapy is
      intensified before surgical revascularization. Nevertheless, our data showed that
      documentation of preoperative OMM did not lead to improved short- or long-term
      postoperative outcomes in these patients, suggesting that more objective measures
      of medical management are needed to ensure that peripheral arterial disease goals
      are achieved.

PMID- 30108009
TI  - Patellar height influences knee function in patients with aggressive bone tumors
      of the proximal tibia after endoprosthetic reconstruction.
AB  - BACKGROUND: The proximal tibia is the second most common site of aggressive bone
      tumors. In proximal tibia resection, the patellar tendon is sectioned one to two
      centimeters from its insertion on the tibial tubercle, which makes it technically
      challenging to achieve an appropriate patellar height and firm fixation of the
      patellar tendon. The purpose of this study was to determine whether the patellar
      height influences knee function after proximal tibia endoprosthetic
      reconstruction (EPR). METHODS: Twenty-nine patients with pathologically confirmed
      aggressive bone tumors in the proximal tibia were retrospectively analyzed. We
      used the Insall-Salvati ratio (ISR) and the Blackburne-Peel index (BPI) to
      radiographically analyze the patellar height. Functional outcomes were
      retrospectively assessed using the Musculoskeletal Tumor Society (MSTS) score,
      the Oxford Knee Score (OKS) and the range of motion (ROM) which was evaluated
      through extensor lag and active flexion. Univariate analysis with Pearson's
      correlation and a multivariate linear regression of patient characteristics and
      surgery-related changes were performed. RESULTS: The postoperative ISRs were
      negatively correlated with the functionality domain of the MSTS score (function,
      gait, walking) and the OKS. Pearson's correlation analysis showed a significant
      correlation between the postoperative ISR and extensor lag. The change in
      patellar height had no impact on the active flexion of the knee. CONCLUSIONS:
      Patellar height is an independent factor contributing to knee function after
      proximal tibia EPR. The quality of patellar tendon reconstruction is a key point
      in proximal tibia EPR after tumor resection.

PMID- 30108010
TI  - Brake response time after modern total knee arthroplasty: How soon can patients
      drive?
AB  - BACKGROUND: Recent advances in the performance of total knee arthroplasty may
      allow for return to driving sooner than the current recommendation of six to
      eight weeks. The purpose of this study was to evaluate at what time point
      patients may safely return to driving after modern total knee arthroplasty.
      METHODS: Thirty-two consecutive patients underwent pre-operative and weekly post
      operative assessments of brake reaction time before and for eight weeks after
      undergoing total knee arthroplasty. RESULTS: Overall, patients returned to their
      preoperative baseline brake reaction times by the second postoperative week.
      There was a significant difference in regard to gender but not laterality or age.
      Specifically, men achieved preoperative brake reaction times by the first
      postoperative week and women by the second. CONCLUSIONS: Patients undergoing
      total knee arthroplasty with a modern perioperative pathway appear to achieve
      preoperative brake reaction times by the second postoperative week when not
      taking narcotic pain medication. However, the safe return to driving in each
      patient must be approached individually. Surgeon discretion to release a patient
      to drive is always prudent and the decision should be considered on an individual
      basis.

PMID- 30108011
TI  - Preoperative opioid medication use negatively affect health related quality of
      life after total knee arthroplasty.
AB  - BACKGROUND: Opioids are commonly prescribed to treat patients suffering from
      painful knee arthritis. However, the opioid epidemic in the United States
      constitutes a major public health concern. This study aims to characterize the
      effect of preoperative opioid use on patient-reported outcome measures (PROMs)
      after total knee arthroplasty (TKA). METHODS: PROMs collected from patients
      undergoing TKA were reviewed. We identified two matched cohorts: (1) 30 patients
      who used opioids preoperatively and (2) 137 patients who did not use opioids
      preoperatively. The non-opioid cohort was carefully selected to match the opioid
      cohort. Statistical analyses were performed to determine the difference in
      demographics, PROMs, length of stay, disposition and co-morbidities between the
      two cohorts. RESULTS: The non-opioid users had significant improvement in both
      EuroQol5D (EQ-5D) PROMs and visual analogy scale (VAS) scores postoperatively (p
      < 0.001); however, preoperative opioid users did not show improvement in either
      measure. University of California Los Angles (UCLA) scores were significantly
      improved for both non-opioid users (p < 0.001) and opioid users (p < 0.001). Non
      opioid users had higher preoperative EQ-5D scores than opioid users (p = 0.02).
      There was no difference in range of motion, length of stay, or disposition
      between cohorts. CONCLUSION: Our results demonstrated that TKA patients with
      preoperative opioid use had significantly lower VAS scores and trends of lower
      UCLA and EQ-5D scores postoperatively compared to non-opioid patients, suggesting
      the use of opioid medications prior to TKA negatively affects patient reported
      outcomes following surgery. The current findings provide useful clinical
      information that can be used in counseling patients prior to undergoing TKA.

PMID- 30108013
TI  - [Hypofractionad radiotherapy for elderly with head and neck cancer].
AB  - Thirty percent of patients with head and neck cancer are over 70 years.
      Radiotherapy approach in elderly is a challenge. On one hand, radiotherapy side
      effects, as well as the number of sessions required, could be a burden. On the
      other hand, omission of local treatment is not an option due to the symptoms of
      the tumor. Patients in good general condition may receive standard fractionnated
      radiotherapy. For frail patients unsuitable for standard fractionated
      radiotherapy, more convenient shorter course of radiotherapy are commonly used.
      Physicians have to choose the best radiotherapy schedule according to the
      objective of the treatment. In case of palliative intend: hypofractionated
      radiotherapy delivered with a single short course could be recommanded. This
      course could be followed by other subsequent courses if the patient's condition
      improves during the treatment. For patients treated in curative intend, the
      choice of hypofractionation schedule depends on the general condition: split
      course hypofractionated radiotherapy for unfit patients, or accelerated
      radiotherapy with concomitant boost for fit patients. In all cases, a high
      quality radiotherapy technique and appropriate supportive care are mandatory to
      minimize the side effects. The ELAN RT trial, soon to be completed, will rule on
      the non-inferiority of hypofractionated radiotherapy compared to standard
      radiotherapy for unfit patients.

PMID- 30108012
TI  - Characteristic morphology of the proximal tibiofibular joint in patients with
      discoid lateral meniscus.
AB  - BACKGROUND: Patients with discoid lateral meniscus (DLM) are prone to meniscal
      injuries related to its shape and abnormal mobility. The anatomical joint
      inclination of the proximal tibiofibular joint (PTFJ) can also affect joint
      movement in knee motion. However, an association between PTFJ morphology and DLM
      remains unclear. The purpose of this study was to investigate the morphology of
      the PTFJ on MRI and how this differs between patients with and without DLM.
      MATERIALS AND METHODS: Fifty-eight patients with DLM and 58 age-matched controls
      (normal meniscus) were included in this study. Slices from preoperative MRI
      sagittal images that clearly showed the PTFJ were used for measurements. The
      angle between the PTFJ and the perpendicular line of the fibula axis was measured
      as the inclination angle, and patients were classified as horizontal-type (<20
      degrees ) or oblique-type (>20 degrees ). The inclination angle was also compared
      among patients with open and closed epiphysis in both groups to assess the effect
      of age. RESULTS: Patients in the horizontal-type PTFJ group frequently had DLM.
      Before epiphyseal closure, most patients had a horizontal-type PTFJ, with or
      without DLM. However, in older patients with a closed epiphysis, most with a
      normal meniscus had an oblique-type PTFJ, and those with DLM retained the
      horizontal-type joint. CONCLUSION: The horizontal-type PTFJ was significantly
      associated with DLM, and patients with DLM tended to retain a horizontal-type
      PTFJ after epiphyseal closure. In contrast, in patients with a normal meniscus,
      the PTFJ may change from a horizontal-type to an oblique-type PTFJ in line with
      bone maturity.

PMID- 30108014
TI  - "I am a Runner": A qualitative analysis of women-runners' pregnancy experiences.
AB  - BACKGROUND: Women runners are a group with potential for health maintenance and
      health promotion in pregnancy. When providers counsel women to discontinue or cut
      back on running without cause, an opportunity for health benefits to both woman
      and baby may be lost. AIM: This study aims to explicate the experience women
      runners have in pregnancy to further providers' understanding of this
      population's unique needs. METHODS: An online, qualitative inquiry was employed
      to explore the experiences of an online community of women runners in pregnancy
      (N=22). The Doing Pregnancy framework provided guidance for final stages of the
      analysis. FINDINGS: Four themes emerged, explicating a process for "Doing
      Pregnancy" as a woman-runner: (1) I am a runner; (2) running tunes me into my
      pregnant body; (3) adjusting to pregnancy's changes; and (4) trusting my
      instincts & knowledge vs. listening to others. DISCUSSION: Women's sense of
      embodiment caused them to feel strongly tuned into the needs of their maternal
      fetal dyad and to trust that they knew what was healthy regarding running during
      pregnancy. When provider advice was conflicting or was not evidence-based, women
      lost trust in their providers. CONCLUSION: Providers caring for women runners
      should recognize running as a key piece of their identities and enter into shared
      partnership as women navigate changes in pregnancy. Women have a strong sense of
      embodiment and are tuned into the needs of their body as well as the needs of
      their baby.

PMID- 30108015
TI  - Clinical Findings and Prognosis of Danon Disease. An Analysis of the Spanish
      Multicenter Danon Registry.
AB  - INTRODUCTION AND OBJECTIVES: Danon disease (DD) is caused by mutations in the
      LAMP2 gene. It is considered a multisystemic disease characterized by
      hypertrophic cardiomyopathy with pre-excitation and extreme hypertrophy,
      intellectual disability, myopathy, childhood presentation, and worse prognosis in
      men. There are scarce data on the clinical characteristics and prognosis of DD.
      METHODS: We analyzed the clinical records of patients with DD from 10 Spanish
      hospitals. RESULTS: Twenty-seven patients were included (mean age, 31 +/- 19
      years; 78% women). Male patients showed a high prevalence of extracardiac
      manifestations: myopathy (80%), learning disorders (83%), and visual alterations
      (60%), which were uncommon findings in women (5%, 0%, and 27%, respectively).
      Although hypertrophic cardiomyopathy was the most common form of heart disease
      (61%), the mean maximum wall thickness was 15 +/- 7 mm and dilated cardiomyopathy
      was present in 12 patients (10 women). Pre-excitation was found in only 11
      patients (49%). Age at presentation was older than 20 years in 16 patients (65%).
      After a median follow-up of 4 years (interquartile range, 2-9), 4 men (67%) and 9
      women (43%) died or required a transplant. Cardiac disease and adverse events
      occurred later in women (37 +/- 9 vs 23 +/- 16 and 36 +/- 20 vs 20 +/- 11 years,
      respectively). CONCLUSIONS: The clinical characteristics of DD differ
      substantially from traditional descriptions: age at presentation of DD is older,
      the disease is not multisystemic in women, and pre-excitation is infrequent.

PMID- 30108016
TI  - MicroRNA-449a suppresses hepatocellular carcinoma cell growth via G1 phase arrest
      and the HGF/MET c-Met pathway.
AB  - BACKGROUND: Accumulating evidence demonstrates that microRNAs (miRNAs) play
      essential roles in tumorigenesis and cancer progression of hepatocellular
      carcinoma (HCC). Average targets of a miRNA were more than 100. And one miRNA may
      act in tumor via regulating several targets. The present study aimed to explore
      more potential targets of miR-449a by proteomics technology and further uncover
      the role of miR-449a in HCC tumorigenesis. METHODS: Technologies such as iTRAQ
      based quantitative proteomic were used to investigate the effect of miR-449a on
      HCC. The expression of c-Met and miR-449a was detected by qRT-PCR in HCC samples.
      Gain- and loss-of-function experiments were performed to identify the function
      and potential target of miR-449a in HCC cells. RESULTS: In HCC, miR-449a was
      significantly downregulated, while c-Met was upregulated concurrently.
      Quantitative proteomics and luciferase reporter assay identified c-Met as a
      direct target of miR-449a. Moreover, miR-449a inhibited HCC growth not only by
      targeting CDK6 but also by suppressing c-Met/Ras/Raf/ERK signaling pathway.
      Furthermore, the inhibition of c-Met expression with a specific siRNA
      significantly inhibited cells growth and deregulated the ERK pathway in HCC.
      CONCLUSION: The tumor suppressor miR-449a suppresses HCC tumorigenesis by
      repressing the c-Met/ERK pathway.

PMID- 30108017
TI  - Glissonian approach combined with major hepatic vein first for laparoscopic
      anatomic hepatectomy.
AB  - BACKGROUND: Laparoscopic anatomic hepatectomy remains challenging because of the
      complex interior structures of the liver. Our novel strategy includes the
      Glissonian approach and the major hepatic vein first, which serves to define the
      external and internal landmarks for laparoscopic anatomic hepatectomy. METHODS:
      Eleven cases underwent laparoscopic anatomic hepatectomy, including three right
      hepatectomies, three left hepatectomies, three right posterior hepatectomies, and
      two mesohepatectomies. The Glissonian approach was used to transect the hepatic
      pedicles as external demarcation. The major hepatic vein near the hepatic portal
      was exposed and served as the internal landmark for parenchymal transection. The
      liver parenchyma below and above the major hepatic vein was transected along the
      major hepatic vein. Fifty-nine subjects were used to compare the distance between
      the major hepatic vein and secondary Glisson pedicles among different liver
      diseases. RESULTS: The average operative time was 327 min with an estimated blood
      loss of 554.55 mL. Only two patients received three units of packed red blood
      cells. The others recovered normally and were discharged on postoperative day 7.
      The distance between right posterior Glissonian pedicle and right hepatic vein
      was shorter in the patients with cirrhosis than that without cirrhosis, and this
      distance was even shorter in patients with hepatocellular carcinoma. CONCLUSION:
      The Glissonian approach with the major hepatic vein first is easy and feasible
      for laparoscopic anatomic hepatectomy, especially in patients with hepatocellular
      carcinoma and cirrhosis.

PMID- 30108018
TI  - New-onset hyperglycemia immediately after liver transplantation: A national
      survey from China Liver Transplant Registry.
AB  - BACKGROUND: New-onset hyperglycemia (NOH) is a common phenomenon after liver
      transplantation (LT), but its impact on clinical outcomes has not yet been fully
      assessed. We aimed to evaluate the etiology and prognosis of NOH within 1 month
      after LT. METHODS: The data of 3339 adult patients who underwent primary LT from
      donation after citizen death between January 2010 and June 2016 were extracted
      from China Liver Transplant Registry database and analyzed. NOH was defined as
      fasting blood glucose >=7.0 mmol/L confirmed on at least two occasions within the
      first post-transplant month with or without hypoglycemic agent. RESULTS: Of 3339
      liver recipients, 1416 (42.4%) developed NOH. Recipients with NOH had higher
      incidence of post-transplant complications such as graft and kidney failure,
      infection, biliary stricture, cholangitis, and tumor recurrence in a glucose
      concentration-dependent manner as compared to non-NOH recipients (P < 0.05). The
      independent risk factors of NOH were donor warm ischemic time >10 min, cold
      ischemic time >10 h, anhepatic time >60 min, recipient model for end-stage liver
      disease score >30, moderate ascites and corticosteroid usage (P < 0.05). Liver
      enzymes (alanine aminotransferase and gamma-glutamyltranspeptidase) on post
      transplant day 7 significantly correlated with NOH (P < 0.001). CONCLUSIONS: NOH
      leads to increased morbidity and mortality in liver recipients. Close
      surveillance and tight control of blood glucose are desiderated immediately
      following LT particularly in those with delayed graft function and receiving
      corticosteroid. Strategic targeting graft ischemic injury may help maintain
      glucose homeostasis.

PMID- 30108019
TI  - Recognizability of computer-generated facial approximations in an automated
      facial recognition context for potential use in unidentified persons data
      repositories: Optimally and operationally modeled conditions.
AB  - Currently in the United States, the remains of thousands of unidentified human
      decedents are housed in medical, law enforcement, and forensic facilities
      throughout the country. A number of digital data repositories have been
      established to curate and disseminate the details of these unidentified decedent
      cases; some repositories also maintain records of missing persons. Although a
      cross-reference for textual data similarity occurs between the missing persons
      and unidentified decedent records in some repositories, no repository is
      currently known to employ an image analysis technology for cross-referencing
      image data. Results suggest that the computer-generated facial approximations
      used in this research were consistently included in prioritized candidate lists
      when used in an automated facial recognition context. Two concurrent studies
      exploring the specific use-case discussed here were executed. The first employed
      an optimally-conditioned facial image gallery (g=6159) (i.e., a gallery comprised
      of highly consistent facial images), a research design intended to establish the
      ceiling performance of the combined use of the two software programs employed.
      The second employed a gallery (g=1816) compiled from a real-world dataset of
      missing persons' facial images, a research design intended to inform potential
      operational performance when using the highly varied facial images typically
      comprising public databases. Multiple types of facial approximations
      (reconstructions) with varying degrees of weight adjustments, age adjustments, or
      the presence (or absence) of visible eyes, and combinations of these variables,
      were evaluated. Overall, in the larger, optimally modeled study, 53% of the
      facial approximations for the t=159 test subjects examined were matched to his or
      her corresponding life photo within the top 50 images of a candidate list
      generated from a blind (unrestricted) search of the highly consistent gallery
      (g=6159). In the operationally modeled study, 31% of the test subjects' (t=16)
      facial approximations were matched to their corresponding life photos within the
      top 50 images of a candidate list generated from a blind search of the gallery
      populated with images from an operational dataset (g=1816). As anticipated,
      candidate list inclusion rates improved with the use of demographic filters. No
      significantly different inclusion rates were observed between the sex or age
      cohorts examined. Significant differences were, however, observed across
      population cohorts. Entities curating missing and unidentified decedent records
      may benefit from a paired implementation of facial recognition technology and
      computer-generated approximations as part of a comprehensive investigative
      strategy for the specific envisioned use-case discussed in this research.

PMID- 30108021
TI  - Association of Clinicopathologic and Molecular Markers on Stage-specific Survival
      of Right Versus Left Colon Cancer.
AB  - BACKGROUND: Previous studies have shown that variability in molecular markers
      correlates with poorer survival outcomes in patients with right-sided colon
      cancer (RCC) compared with left-sided colon cancer (LCC). However, several
      studies have shown conflicting results when examined stage for stage. We examined
      RCC and LCC to assess for differences in histopathologic features and overall
      survival (OS). MATERIALS AND METHODS: The National Cancer Database was used to
      identify patients with RCC and LCC from 2004 to 2013. A propensity-adjusted
      analysis evaluating the association between the primary site and OS was
      performed. RESULTS: Of the 422,443 patients identified, 54.7% had RCC and 45.3%
      had LCC. For all stages, the patients with RCC were older, had more poorly
      differentiated tumors, and had a greater degree of microsatellite instability
      compared with those with LCC. Patients with RCC also had more KRAS mutations than
      did those with LCC. RCC patients had poorer 3- and 5-year OS at all stages,
      especially stage 3 (62% vs. 73% and 50% vs. 62%, respectively; P < .001). The
      median OS was 77.5 months for LCC and 62.3 months for RCC (P < .001). CONCLUSION:
      The present study is one of the largest studies demonstrating that RCC and LCC
      are different biologic entities. Patients with RCC had significantly greater
      rates of microsatellite instability for all stages, which has been previously
      shown to be prognostically advantageous. However, the results of the present
      study showed poorer OS at every disease stage for RCC compared with LCC. These
      factors have important implications for the further use of targeted therapies in
      the treatment of advanced colon cancer.

PMID- 30108020
TI  - Genetic Diversity and Population Structure of Cryptosporidium.
AB  - Cryptosporidium species differ in host range. Parasite-host coevolution, host
      adaptation, and geographic segregation have led to the formation of subtype
      families with unique phenotypic traits within the major human-pathogenic species
      C. parvum and C. hominis. Transmission intensity, genetic diversity, and
      occurrence of genetic recombination and selective pressure have further shaped
      their population genetic structures. Panmixia appears to be common within the
      zoonotic C. parvum, especially its hypertransmissible IIaA15G2R1 subtype. Genetic
      recombination in C. hominis, in contrast, is more restricted to virulent
      subtypes, especially IbA10G2. Nonhuman primates and equine animals are commonly
      infected with genetically divergent C. hominis populations. Systematic studies of
      these and other host-adapted Cryptosporidium spp. are likely leading to improved
      understanding of population structures underlying various transmission patterns
      and intensities of Cryptosporidium.

PMID- 30108022
TI  - Spectral Doppler Analysis of the HeartMate 3 Left Ventricular Assist Device
      Inflow: New Challenges Presented by the Artificial Pulse Technology.

PMID- 30108023
TI  - Patients with pancreatic cystic neoplasms can benefit from management of
      multidisciplinary team: Experience from a Chinese academic center.
AB  - BACKGROUND: Pancreatic cystic neoplasms (PCNs) are a spectrum of neoplasms that
      can be benign or malignant. The accuracy of diagnosis is critical for this
      disease since different types of PCNs are treated differently using various
      modalities. The use of a multidisciplinary team (MDT) has been shown to improve
      the management and outcomes of various diseases. We aimed to determine the
      performance of MDT in the management of PCNs. METHODS: We retrospectively
      reviewed 167 pathologically-proven PCN patients and divided them among three
      groups according to their surgical data and treatment modalities: 1) historical
      control group (HC group); 2) concurrent control group (CC group); and 3) MDT
      group. The composition of subtypes of PCNs, preoperative diagnostic accuracy,
      postoperative complications, and postoperative hospital stay were compared among
      the three groups. RESULTS: The incidence of SCN reduced in the MDT group, while
      the incidence of IPMN was much higher (P < 0.05). MDT management significantly
      improved the accuracy of preoperative diagnosis (71.7%) and also increased the
      individual diagnostic accuracies of ultrasound, CT, and MRI/MRCP. Postoperative
      pancreatic fistula was significantly reduced in the MDT group (28.3%; P < 0.001).
      Furthermore, the mean hospital stay after surgery in the MDT group (10.37 days)
      was shorter than those of the other two groups (27.35 days in HC group, and 19.28
      days in CC group; P < 0.05). CONCLUSION: For patients with PCN, MDT management
      was associated with an improvement in the overall accuracy of preoperative
      diagnosis, a lower incidence postoperative morbidity, and decreased length of
      hospital stay.

PMID- 30108024
TI  - The Effect of the Affordable Care Act's Dependent Coverage Provisionon Health
      Insurance Gaps for Young Adults With SpecialHealthcare Needs.
AB  - PURPOSE: This study examined the impact of the 2010 Affordable Care Act's
      dependent coverage provision on gaps in insurance coverage for young adults with
      special healthcare needs (YASHCN). METHODS: We used the 2008 Survey on Income and
      Program Participation, a longitudinal survey covering 2008-2013. Our sample was
      comprised of 3,316 YASHCN ages 19-29. We used a difference-in
      differenceregression approach to assess the effect of the dependent coverage
      provision on the probability that a YASHCN experienced a gap in insurance
      coverage. We compared outcomes for a treatment group, YASHCN ages 19-25, and a
      control group, YASHCN ages 27-29, before and after the 2010 policy change. The
      longitudinal data allow us to estimate regressions that control for individual
      and time fixed effects. RESULTS: After controlling for fixed effects and other
      confounding variables, we found that extending coverage until age 26 for YASHCN
      was associated with reduced insurance gaps. Specifically, our estimates suggest
      that the Affordable Care Act dependent coverage provision was associated with
      reduced insurance gaps among YASHCN by 2.4 percentage points. CONCLUSIONS: The
      Affordable Care Act dependent coverage provision helped mitigate the number
      ofinsurance gaps experienced by YASHCN. This is of particular importance to
      YASHCN, as they are a vulnerablepopulation and their continuity of insurance
      coverage is a critical part of their transition into adulthood.

PMID- 30108025
TI  - Association between Type I interferon and depletion and dysfunction of
      endothelial progenitor cells in C57BL/6 mice deficient in both apolipoprotein E
      and Fas ligand.
AB  - Patients with systemic lupus erythematosus (SLE) have a tremendously increased
      risk for cardiovascular disease (CVD), which could not be accounted in entirety
      by traditional Framingham risk factors. To study whether the accelerated
      atherosclerosis in SLE patients is mediated by type I interferon (IFN-I) through
      the regulation of endothelial progenitor cells (EPCs), we created a line of
      C57BL/6 mice with deficiency in both apolipoprotein E (ApoE-/-) and fas ligand
      (FasL-/-, gld.). As expected, the resultant gld. ApoE-/- mice exhibited both
      aggravated lupus-like disease and atherosclerosis under normal diet. Increased
      expression of IFN-I-stimulated genes (ISGs) was closely associated with depletion
      and dysfunction of EPCs, as well as with accelerated atherosclerotic lesion in
      gld. ApoE-/- mice. While only IFN-alpha instead of other interventions, including
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IRS423 and
      IRS661, impaired EPC function in vitro. Mechanistically, activation or inhibition
      of the TLR7/9 signaling could modulate EPC number and function in vivo. Decreased
      proliferation rate and increased apoptotic rate of EPCs induced by IFN-alpha
      might contribute to the results to a certain extent. Thus, our data suggest that
      excessive expression of IFN-I through the activation of TLR7/9 signaling may
      induce accelerated atherosclerosis in lupus through the depletion or dysfunction
      of EPCs, suggesting that targeting IFN-I might have potential therapeutic effects
      on both lupus disease and premature atherosclerosis in SLE patients.

PMID- 30108026
TI  - Schnitzler syndrome co-occurring with idiopathic multicentric Castleman disease
      that responds to anti-IL-1 therapy: A case report and clue to pathophysiology.
AB  - Patients with HHV-8-negative/idiopathic multicentric Castleman disease (iMCD)
      experience systemic inflammatory symptoms and polyclonal lymphoproliferation due
      to an unknown etiology. Schnitzler's syndrome (SS) is characterized by recurrent
      urticarial rash, monoclonal IgM gammopathy, and other clinical signs of
      inflammation. To our knowledge, we report the first case of iMCD associated with
      SS and the fourth case of anakinra inducing a complete response for an iMCD
      patient. A forty-four year old woman with a history of a recurrent urticarial
      rash, presented to our hospital complaining of 6 months of night sweats, fever,
      chronic urticaria, iliac bone pain, and generalized lymphadenopathy. An IgM Kappa
      monoclonal component was measured at 7.8g/L. A lymph node biopsy revealed
      histopathological features consistent with the plasma cell variant of iMCD. She
      was diagnosed with SS and iMCD. Anti-IL-1 treatment with anakinra (100mg/day) was
      introduced. Within 48h, we observed improvement in the fever and the urticarial
      rash. By one month, we considered the patient in complete remission. Two years
      later, the remission is persistent while the patient is still under therapy.
      Though this is only the fourth reported case of anakinra in iMCD, this is yet
      another case demonstrating the effectiveness of anti-IL-1 blockade in SS. We
      hypothesize that uncontrolled cytokine production is responsible for both the SS
      and the iMCD. The etiologies of SS and iMCD are unknown, and future research is
      necessary.

PMID- 30108028
TI  - Can platelet-rich fibrin improve healing after surgical treatment of medication
      related osteonecrosis of the jaw? A pilot study.
AB  - OBJECTIVE: The aim of this study was to evaluate the efficacy of platelet-rich
      fibrin (PRF) after bone surgery compared to surgery alone in the treatment of
      medication-related osteonecrosis of the jaw (MRONJ). STUDY DESIGN: A total of 47
      patients with diagnosis of stage II or III of MRONJ were recruited at the
      Academic Hospital of Magna Graecia University of Catanzaro and allocated to 2
      groups: In the first, patients were treated with PRF in addition to surgery (PRF
      group), in the other, only bone surgery was performed (non-PRF group). Fisher's
      exact and Student t tests were used to evaluate differences between the 2
      surgical protocols in terms of mucosal integrity, absence of infection, and pain
      evaluation at scheduled follow-ups of 1 month (T1), 6 months (T2), and 1 year
      (T3). RESULTS: Analysis of mucosal integrity, absence of infection, and pain
      evaluation showed a significant difference between the 2 groups in favor of PRF
      only at T1 (P < .05), whereas no differences were determined at T2 and T3 (P >
      .05). CONCLUSIONS: Our results suggested that local application of PRF after bone
      surgery may improve the quality of life limited to the short-term follow-up and
      reduce pain and postoperative infections.

PMID- 30108027
TI  - Serum- and glucocorticoid-inducible kinase 3 is a potential oncogene in
      nasopharyngeal carcinoma.
AB  - INTRODUCTION: Serum- and glucocorticoid-inducible kinase 3, a serine/threonine
      kinase that functions downstream of the PI3K signaling pathway, plays a critical
      role in neoplastic processes. It is expressed by various tumors and contributes
      to carcinogenesis. OBJECTIVE: The objective was to investigate serum- and
      glucocorticoid-inducible kinase 3 expression in nasopharyngeal carcinoma, to
      study the anti-tumor effects of serum- and glucocorticoid-inducible kinase 3
      shRNA by inhibiting its expression in nasopharyngeal carcinoma cells and to
      discuss the potential implications of our findings. METHODS: Serum- and
      glucocorticoid-inducible kinase 3 protein expression in nasopharyngeal carcinoma
      cell lines (CNE-1, CNE-2, HNE-1, HONE-1, and SUNE-1) and the human immortalized
      nasopharyngeal epithelium cell line NP69 were assayed by western blotting. Serum-
      and glucocorticoid-inducible kinase 3 expression in 42 paraffin-embedded
      nasopharyngeal carcinoma tissues were performed by immunohistochemistry. MTT
      assay, flow cytometry, and scratch tests were performed after CNE-2 cells were
      transfected with the best serum- and glucocorticoid-inducible kinase 3 shRNA
      plasmid selected by western blotting using lipofectamine to study its effect on
      cell proliferation, apoptosis, and migration. RESULTS: Serum- and glucocorticoid
      inducible kinase 3 was overexpressed in human nasopharyngeal carcinoma tissues
      and cells. Serum- and glucocorticoid-inducible kinase 3 expression decreased
      markedly after CNE-2 cells were transfected with the serum- and glucocorticoid
      inducible kinase 3 shRNA, leading to strong inhibition of cell proliferation and
      migration. In addition, the apoptosis rate increased in CNE-2 cells after serum-
      and glucocorticoid-inducible kinase 3 knockdown. CONCLUSION: Serum- and
      glucocorticoid-inducible kinase 3 expression was more frequently observed as the
      nasopharyngeal epithelium progresses from normal tissue to carcinoma. This
      suggests that serum- and glucocorticoid-inducible kinase 3 contributes to the
      multistep process of NPC carcinogenesis. Serum- and glucocorticoid-inducible
      kinase 3 represents a target for nasopharyngeal carcinoma therapy, and a basis
      exists for the further investigation of this adjuvant treatment modality for
      nasopharyngeal carcinoma.

PMID- 30108029
TI  - Long-Term Clinical Outcomes of Percutaneous Transluminal Angioplasty with
      Optional Stenting in Patients with Superficial Femoral Artery Disease: A
      Retrospective, Observational Analysis.
AB  - BACKGROUND AND OBJECTIVE: The recent ESC guideline advises primary stent
      placement in superficial femoral arterial disease (SFAD). The aim of this study
      was to compare clinical outcomes of SFAD patients selected for stent placement
      with plain percutaneous transluminal angioplasty (PTA). MATERIALS AND METHODS: A
      single centre retrospective, observational analysis was performed of all
      consecutive patients undergoing endovascular treatment for SFAD from 2004 to
      2015. Primary endpoints were primary and secondary clinical patency rates in
      patients with or without stent placement. Secondary endpoints were recurrence
      rates and number of amputations. Kaplan-Meier curves were used to compare patency
      rates. Multivariable Cox regression analysis was performed to adjust for
      confounding variables and to identify variables associated with loss of patency.
      RESULTS: A total of 389 patients were analysed with a median follow up of 42
      months. Two hundred and fifty one patients (64.5%) were stented. Primary clinical
      patency rates at 1, 3, and 5 years were 82.8%, 71.0%, and 65.6% after PTA and
      76.3%, 65.7%, and 58.1% after stent placement (PTA-S), respectively (p = .30).
      Secondary patency rates were also comparable for the PTA and PTA-S group
      resulting in 1, 3 and 5 year clinical secondary patency of 89.1%, 81.0%, and
      76.3% in the PTA group versus 87.8%, 78.5%, and 71.9% in the PTA-S group (p =
      .58). Multivariable analysis revealed equal primary and secondary clinical
      patency between the treatment groups. The absolute re-intervention rate was
      29.3%. The number of re-interventions and amputation rate did not significantly
      differ between the two groups (p = .41 and p = .75). CONCLUSIONS: Selective
      stenting in patients with SFAD shows comparable results in long-term clinical
      outcomes in patients who were treated with plain PTA as well as patients who are
      selected for stent placement. An approach of selective stenting is justified.

PMID- 30108030
TI  - Vein diameter is a predictive factor for recanalization in treatment with
      ultrasound-guided foam sclerotherapy.
AB  - OBJECTIVE: Ultrasound-guided foam sclerotherapy (UGFS) is a low-cost and
      minimally invasive treatment option for varicose veins. There is a relative
      paucity of outcome reports. METHODS: UGFS procedures at a tertiary public
      hospital between 2010 and 2017 were studied. Either the great saphenous vein
      (GSV) or small saphenous vein (SSV) was treated. Pretreatment, in-treatment, 6
      week, and 1-year post-treatment ultrasound reports were analyzed. The primary
      outcome was to determine whether vein diameter predicts obliteration failure.
      RESULTS: There were 457 treatments completed in 290 patients. The GSV was
      targeted in 372 (81%). Mean vein diameters of the GSV were not different from
      those of the SSV (GSV, 5.7 mm; SSV, 6.2 mm; P = .18); 109 (24%) had a Clinical,
      Etiology, Anatomy, and Pathophysiology score of at least 4. Of the 457 UGFS
      procedures, 360 (78.8%) were for primary veins. Baseline information, including
      vein diameter, was not different between primary and recurrent veins. At 6 weeks,
      complete obliteration, partial recanalization, and complete recanalization rates
      were 54.9%, 29.1%, and 16%, respectively. Of those with complete obliteration at
      6 weeks, the recanalization rate at 1 year was 25%. Increasing vein diameter was
      associated with recanalization at 1 year (obliteration, 4.9 mm; recanalization,
      5.7 mm; P = .03), especially for primary veins (4.8 vs 5.8 mm; P = .009).
      Multivariate analysis showed similar outcome. Vein diameter of >6 mm had good
      specificity (88%) but poor sensitivity (43%) for predicting obliteration failure.
      There were 15 (3%) new-onset deep venous thromboses reported on follow-up, all of
      which were from treatment of primary veins (P = .049). CONCLUSIONS: Only 44% of
      UGFS procedures were observed to have complete obliteration at 1 year after a
      single intervention. Significant recanalization developed at 1 year. Increased
      vein diameter was associated with recanalization. The impact on clinical
      recurrence is unknown.

PMID- 30108031
TI  - Short-term foot complications in Charcot neuroarthropathy: A retrospective study
      in tertiary care centres in Spain.
AB  - OBJECTIVES: To assess the clinical characteristics of patients with Charcot
      neuroarthropathy (CN) in Spain and to identify predictors for CN-related
      complications. PATIENTS AND METHODS: A retrospective study was conducted at five
      tertiary hospitals with diabetic foot care units in Spain. Data were collected
      from 83 patients, including demographic profiles, foot factors, diabetes
      characteristics, and presence of microvascular and macrovascular comorbidity, and
      a podiatric examination was also performed. Logistic regression analyses were
      used to determine significant predictors of the predefined clinical events.
      RESULTS: Signs of diabetic neuropathy were found in almost all patients (98.9%)
      at the initial assessment, approximately half of them had diabetic retinopathy or
      nephropathy (61.5% and 51.8%, respectively), and peripheral artery disease was
      uncommon (8.6%). Thirty-eight patients (47.5%) experienced one or more relevant
      clinical events: 22 (27.5%) a new foot ulcer; 7 (8.7%) a major amputation; 20
      (25%) were admitted to hospital; and 4 (5%) died. Only the presence of diabetic
      nephropathy was independently associated to development of any of the
      complications studied (p = 0.009; odds ratio = 3.37; 95% CI: 1.12-10.1).
      CONCLUSIONS: Almost half the patients with CN attending specialised foot care
      units in tertiary hospitals experienced short-term CN-associated complications,
      and the risk was 3 times higher in those with a history of diabetic nephropathy.

PMID- 30108032
TI  - Deprescribing Medications for Chronic Diseases Management in Primary Care
      Settings: A Systematic Review of Randomized Controlled Trials.
AB  - OBJECTIVES: Perform a systematic review to evaluate the outcome of deprescription
      compared with standard care. The focus was on chronic medical and mental health
      conditions managed in primary care. DESIGN: The databases searched include
      PubMed, Medline, EMBASE, the Cochrane Library, Scopus, and Web of Science. Each
      study was assessed for bias with the Cochrane Collaboration tool. SETTINGS AND
      PARTICIPANTS: This review included outpatient, assisted living, nursing home, and
      acute care settings (if medications for chronic disease were deprescribed).
      Subjects were non-terminally ill adults 18 years and older. MEASURES: Primary
      outcome was successful deprescription, defined as a statistically significant
      reduction in medication burden between the intervention group and the standard
      care or control group, or when more than 50% of intervention subjects were able
      to tolerate medication discontinuation compared with control by the end of the
      study. RESULTS: Fifty-eight articles met the study criteria. Thirty-three (58%)
      had a high risk of bias. Studies varied in duration from 4 weeks to 5 years and
      were conducted across a diverse array of primary health care settings. The most
      successful interventions used pharmacist-led educational interventions and
      patient-specific drug recommendations. Cardiovascular drugs including
      antihypertensives/diuretics and nitrates were the most successfully deprescribed
      class of drugs. Psychotropic medications and proton-pump inhibitors were the
      classes most resistant to deprescribing, despite intense intervention.
      CONCLUSIONS/IMPLICATIONS: Deprescription may be successful and effective in
      select classes of drugs, with collaboration of clinical pharmacists for patient
      and provider education, and patient-specific drug recommendations, complemented
      by close clinical follow-up to detect early signs of exacerbation of chronic
      diseases. This review also suggests that deprescription may (1) require expensive
      intensive, ongoing interventions by clinical teams; (2) not lead to expected
      outcomes such as improved falls rate, cognition, and quality of life, or a lower
      admission rate; and (3) have unexpected adverse outcomes affecting patients'
      quality of life.

PMID- 30108033
TI  - An Analysis of Falls and Those who Fall in a Chronic Care Facility.
AB  - OBJECTIVES: Falls in hospitals lead to adverse patient outcomes and prevention of
      falls is of upmost importance. Little is known about fall and injury rates in
      chronic care facilities, which are similar to skilled nursing facilities in the
      United States. Current fall risk tools in this setting are not well studied.
      Enhancing the understanding of how patient characteristics relate to fall
      circumstances is also needed. DESIGN: Retrospective analysis of falls over 3
      years on consecutive admissions and discharges. SETTING AND PARTICIPANTS: A 104
      bed geriatric chronic care facility. MEASURES: Fall and injury data, descriptive
      data for patients measuring mobility, balance, cognition, function, and frailty
      in relation to risk of falls and fall circumstances were analyzed. RESULTS: There
      were 1141 falls, with an overall fall rate of 8.48 falls per 1000 occupied bed
      days. The overall injury rate was 37.2 injuries per 100 falls. Being male and
      frail, having a mobility aid, poor mobility, balance, or cognition were
      associated with falling. Patients with good balance but poor cognition was more
      likely to fall outside their room, while those with poor mobility/balance fell
      more often in their room. The Clinical Frailty Scale performed modestly well at
      predicting falls with an odds ratio of 2.5 (95% confidence interval 1.9-3.2).
      CONCLUSIONS AND IMPLICATIONS: Fall rates in chronic care facilities differ from
      what is reported in other settings. Patient characteristics such as male, use or
      misuse of a mobility aid, and poor cognition are more common in fallers. Fall
      circumstances differ in those with poor cognition compared with those with poor
      mobility and balance. More research focusing on frailty, cognition, and
      mobility/balance is needed to develop accurate tools that can predict those at a
      high risk of falls in these facilities.

PMID- 30108034
TI  - One Week of Hospitalization Following Elective Hip Surgery Induces Substantial
      Muscle Atrophy in Older Patients.
AB  - OBJECTIVES: Short successive periods of skeletal muscle disuse have been
      suggested to substantially contribute to the observed loss of skeletal muscle
      mass over the life span. Hospitalization of older individuals due to acute
      illness, injury, or major surgery generally results in a mean hospital stay of 5
      to 7 days, during which the level of physical activity is strongly reduced. We
      hypothesized that hospitalization following elective total hip arthroplasty is
      accompanied by substantial leg muscle atrophy in older men and women. DESIGN AND
      PARTICIPANTS: Twenty-six older patients (75 +/- 1 years) undergoing elective
      total hip arthroplasty participated in this observational study. MEASUREMENTS: On
      hospital admission and on the day of discharge, computed tomographic (CT) scans
      were performed to assess muscle cross-sectional area (CSA) of both legs. During
      surgery and on the day of hospital discharge, a skeletal muscle biopsy was taken
      from the m. vastus lateralis of the operated leg to assess muscle fiber type
      specific CSA. RESULTS: An average of 5.6 +/- 0.3 days of hospitalization resulted
      in a significant decline in quadriceps (-3.4% +/- 1.0%) and thigh muscle CSA (
      4.2% +/- 1.1%) in the nonoperated leg (P < .05). Edema resulted in a 10.3% +/-
      1.7% increase in leg CSA in the operated leg (P < .05). At hospital admission,
      muscle fiber CSA was smaller in the type II vs type I fibers (3326 +/- 253 MUm2
      vs 4075 +/- 279 MUm2, respectively; P < .05). During hospitalization, type I and
      II muscle fiber CSA tended to increase, likely due to edema in the operated leg
      (P = .10). CONCLUSIONS: Six days of hospitalization following elective total hip
      arthroplasty leads to substantial leg muscle atrophy in older patients. Effective
      intervention strategies are warranted to prevent the loss of muscle mass induced
      by short periods of muscle disuse during hospitalization.

PMID- 30108035
TI  - Evaluation of Nursing Facility Resident Safety During Implementation of the
      INTERACT Quality Improvement Program.
AB  - BACKGROUND: Medicare incentivizes the reduction of hospitalizations of nursing
      facility (NF) residents. The effects of these incentives on resident safety have
      not been examined. OBJECTIVE: Examine safety indicators in NFs participating in a
      randomized, controlled trial of the INTERACT Quality Improvement Program. DESIGN:
      Secondary analysis of a randomized trial in which intervention NFs exhibited a
      statistically nonsignificant reduction in hospitalizations. SETTING: NFs with
      adequate on-site medical, radiography, laboratory, and pharmacy services, and
      capability for online training and data input were eligible. PARTICIPANTS: 264
      NFs randomized into intervention and comparison groups stratified by previous
      INTERACT use and self-reported hospital readmission rates. INTERVENTION: NFs
      randomized to the intervention group received INTERACT materials, access to
      online training and a series of training webinars, feedback on hospitalization
      rates and root-cause analysis data, and monthly telephonic support. MEASURES:
      Minimum data set (MDS) data for unintentional weight loss, malnutrition, hip
      fracture, pneumonia, wound infection, septicemia, urinary tract infection, and
      falls with injury for the intervention year and the year prior; unintentional
      weight loss, dehydration, changes in rates of falls, pressure ulcers, severe
      pain, and unexpected deaths obtained from the NFs participating in the
      intervention through monthly telephone calls. RESULTS: No adverse effects on
      resident safety, and no significant differences in safety indicators between
      intervention and comparison group NFs were identified, with 1 exception.
      Intervention NFs with high levels of INTERACT tool use reported significantly
      lower rates of severe pain. CONCLUSIONS/IMPLICATIONS: Resident safety was not
      compromised during implementation of a quality improvement program designed to
      reduce unnecessary hospitalization of NF residents.

PMID- 30108038
TI  - Alternative to pethidine could halve rate of epidurals.

PMID- 30108036
TI  - Information and Communication Technologies Interest, Access, and Use: Cross
      Sectional Survey of a Community Sample of Urban, Predominantly Black Women.
AB  - BACKGROUND: Information and communication technologies (ICT) offer the potential
      for delivering health care interventions to low socioeconomic populations who
      often face barriers in accessing health care. However, most studies on ICT for
      health education and interventions have been conducted in clinical settings.
      OBJECTIVE: The aim of this study was to examine access to and use of mobile
      phones and computers, as well as interest in, using ICT for receipt of behavioral
      health information among a community sample of urban, predominately black, women
      with low socioeconomic status. METHODS: Participants (N=220) were recruited from
      hair salons and social service centers and completed audio-computer assisted self
      interviews. RESULTS: The majority of the participants (212/220, 96.3%) reported
      use of a cell phone at least weekly, of which 89.1% (189/212) used smartphones
      and 62.3% (137/220) reported computer use at least weekly. Of the women included
      in the study, 51.9% (107/206) reported using a cell phone and 39.4% (74/188)
      reported using a computer to access health and/or safety information at least
      weekly. Approximately half of the women expressed an interest in receiving
      information about stress management (51%-56%) or alcohol and health (45%-46%) via
      ICT. Smartphone ownership was associated with younger age (odds ratio [OR] 0.92,
      95% CI 0.87-0.97) and employment (OR 5.12, 95% CI 1.05-24.95). Accessing health
      and safety information weekly by phone was associated with younger age (OR 0.96,
      95% CI 0.94-0.99) and inversely associated with higher income (OR 0.42, 95% CI
      0.20-0.92). CONCLUSIONS: Our findings suggest that ICT use, particularly
      smartphone use, is pervasive among predominantly black women with low
      socioeconomic status in urban, nonclinical settings. These results show that ICT
      is a promising modality for delivering health information to this population.
      Further exploration of the acceptability, feasibility, and effectiveness of using
      ICT to disseminate behavioral health education and intervention is warranted.

PMID- 30108039
TI  - Emergency department closures do not lead to more deaths, study finds.

PMID- 30108037
TI  - A Dietary Management System Using Radio-Frequency Identification Technology to
      Collect Information on Chinese Food Consumption: Development and Feasibility
      Study.
AB  - BACKGROUND: Dietary management is important for personal health. However, it is
      challenging to record quantified food information in an efficient, accurate, and
      sustainable manner, particularly for the consumption of Chinese food. OBJECTIVE:
      The objective of this study was to develop a dietary management system to record
      information on consumption of Chinese food, which can help in assessing
      individuals' dietary intake and maintaining healthy eating behaviors. We proposed
      to use plates embedded with radio-frequency identification chips to carry Chinese
      foods and collect food consumption data. METHODS: We obtained food composition
      and nutrient (eg, carbohydrate, fat, fiber) data from the Chinese Recipe Database
      and China Food Composition Database. To test the feasibility of the dietary
      management system at a population level, we applied it to collect data on 489
      Chinese foods that were consumed at lunchtime across 7 weeks by 10,528
      individuals. To test individual-level output, we selected an individual
      participant with completed 20-day dietary data for analysis. We examined the
      system's nutrient calculation performance by comparing the nutrient values of 3
      selected Chinese dishes calculated by our method with the results of chemical
      measurements. RESULTS: We collected the dietary intake for a group of 10,528
      individuals aged from 20 to 40 years having lunch in a restaurant across 7 weeks.
      A total of 489 Chinese dishes were identified. We analyzed a specified customer's
      diet recordings and broke his or her 20 lunch diet recordings down to ingredients
      and then to nutrient intake. We compared the nutrient value of a given Chinese
      dish (eg, garlic puree cooked pork leg) calculated by our method with the results
      of chemical measurements. The mean absolute percentage deviation showed that our
      method enabled collection of dietary intake for Chinese foods. CONCLUSIONS: This
      preliminary study demonstrated the feasibility of radio-frequency identification
      based dietary management for Chinese food consumption. In future, we will
      investigate factors such as preparation method, weight of food consumed, and
      auxiliary ingredients to improve dietary assessment accuracy.

PMID- 30108040
TI  - Tribunal made error in allowing psychiatrist back on register, says appeal court.

PMID- 30108041
TI  - CPR decision-making conversations in the UK: an integrative review.
AB  - OBJECTIVES: Do Not Attempt Cardio-Pulmonary Resuscitation (DNACPR) discussions
      with patients and their caregivers have been subjected to intense ethical and
      legal debate in recent years. Legal cases and national guidelines have tried to
      clarify the best approach to DNACPR discussions; however, there is little
      evidence of how best to approach them from the patient, family or caregiver
      perspective. This paper describes published accounts of patient, family and
      caregiver experiences of discussions about advance cardiopulmonary resuscitation
      (CPR) decision making. METHODS: An integrative review of the UK literature
      between 2000 and 2016 including qualitative and quantitative studies was
      conducted. Worldwide, 773 abstracts were identified, and 20 papers from the UK
      were included in the final analysis. RESULTS: Patient, family and caregivers
      prefer discussions to be initiated by someone trusted, and wishes for family
      involvement vary depending on the context. Timing of discussions should be
      individualised, though discussions earlier in the illness are often preferable.
      Discussions held in the acute setting are suboptimal. CPR decisions should be
      part of a wider discussion about future care and adequate communication skills
      training is important. CONCLUSIONS: The findings of this review are at odds with
      the current statutory framework and potentially challenging for medical
      professionals who are working in a stretched health service, with pressure to
      discuss DNACPR decisions at the earliest opportunity. With increasing focus on
      person-centred care and realistic medicine, patient narratives must be considered
      by doctors and policy makers alike, to minimise harm.

PMID- 30108043
TI  - Hadiza Bawa-Garba wins right to practise again.

PMID- 30108042
TI  - 'Place bonding' in children's hospice care: a qualitative study.
AB  - BACKGROUND: Limited knowledge exists of parents' perceptions and experiences of
      children's hospices and how these contribute to the varied access and uptake of
      services. AIM: This study aimed to explore parents' perspectives and experiences
      of a hospice, to understand the barriers and/or facilitators to accessing a
      hospice, and what characteristics parents wanted from hospice provision. METHODS:
      A two-phase qualitative study underpinned by a constructivist grounded theory
      methodology was employed. Phase 1 used focus groups to collect data from parents
      of children already accessing the hospice (n=24). Phase 2 used in-depth
      semistructured interviews with parents of children who did not use the hospice
      (n=7) and with parents who had previous experience of using a hospice (n=7).
      RESULTS: A grounded theory of place bonding was developed which illustrates the
      cognitive journey taken by parents of children with life-limiting conditions
      considering/receiving hospice care for their child. CONCLUSIONS: Finding a place
      where they belonged and felt at 'home' made the decision to accept help in caring
      for their child with a life-limiting condition more acceptable. The theory of
      place bonding offers children's hospices a new perspective from which to view how
      parents access, accept and build relationships at the hospice.

PMID- 30108044
TI  - Sixty seconds on . . . tongue splitting.

PMID- 30108046
TI  - Secretory form of rheumatoid arthritis-associated autoantibodies in serum are
      mainly of the IgM isotype, suggesting a continuous reactivation of autoantibody
      responses at mucosal surfaces.

PMID- 30108047
TI  - Diagnosis and management of venous leg ulcers.

PMID- 30108045
TI  - Loss of CXCR4 in Myeloid Cells Enhances Antitumor Immunity and Reduces Melanoma
      Growth through NK Cell and FASL Mechanisms.
AB  - The chemokine receptor, CXCR4, is involved in cancer growth, invasion, and
      metastasis. Several promising CXCR4 antagonists have been shown to halt tumor
      metastasis in preclinical studies, and clinical trials evaluating the
      effectiveness of these agents in patients with cancer are ongoing. However, the
      impact of targeting CXCR4 specifically on immune cells is not clear. Here, we
      demonstrate that genetic deletion of CXCR4 in myeloid cells (CXCR4MyeDelta/Delta)
      enhances the antitumor immune response, resulting in significantly reduced
      melanoma tumor growth. Moreover, CXCR4MyeDelta/Delta mice exhibited slowed tumor
      progression compared with CXCR4WT mice in an inducible melanocyte BrafV600E/Pten 
      /- mouse model. The percentage of Fas ligand (FasL)-expressing myeloid cells was
      reduced in CXCR4MyeDelta/Delta mice as compared with myeloid cells from CXCR4WT
      mice. In contrast, there was an increased percentage of natural killer (NK) cells
      expressing FasL in tumors growing in CXCR4MyeDelta/Delta mice. NK cells from
      CXCR4MyeDelta/Delta mice also exhibited increased tumor cell killing capacity in
      vivo, based on clearance of NK-sensitive Yac-1 cells. NK cell-mediated killing of
      Yac-1 cells occurred in a FasL-dependent manner, which was partially dependent
      upon the presence of CXCR4MyeDelta/Delta neutrophils. Furthermore, enhanced NK
      cell activity in CXCR4MyeDelta/Delta mice was also associated with increased
      production of IL18 by specific leukocyte subpopulations. These data suggest that
      CXCR4-mediated signals from myeloid cells suppress NK cell-mediated tumor
      surveillance and thereby enhance tumor growth. Systemic delivery of a peptide
      antagonist of CXCR4 to tumor-bearing CXCR4WT mice resulted in enhanced NK-cell
      activation and reduced tumor growth, supporting potential clinical implications
      for CXCR4 antagonism in some cancers. Cancer Immunol Res; 6(10); 1186-98. (c)2018
      AACR.

PMID- 30108048
TI  - Correction to "Metabolism and Disposition of a Novel Selective alpha7 Neuronal
      Acetylcholine Receptor Agonist ABT-126 in Humans: Characterization of the Major
      Roles for Flavin-Containing Monooxygenases and UDP-Glucuronosyl Transferase 1A4
      and 2B10 in Catalysis".

PMID- 30108049
TI  - Renaming junior doctors: five minutes with Scarlett McNally.

PMID- 30108050
TI  - Should we stop prescribing "just in case" drugs in terminal care?

PMID- 30108052
TI  - David Oliver: Private practice by NHS doctors-still controversial?

PMID- 30108051
TI  - Soluble endoglin regulates expression of angiogenesis-related proteins and
      induction of arteriovenous malformations in a mouse model of hereditary
      hemorrhagic telangiectasia.
AB  - Endoglin is a transmembrane glycoprotein expressed in vascular endothelium that
      plays a key role in angiogenesis. Mutations in the endoglin gene (ENG) cause
      hereditary hemorrhagic telangiectasia type 1 (HHT1), characterized by
      arteriovenous malformations (AVMs) in different organs. These vascular lesions
      derive from abnormal processes of angiogenesis, whereby aberrant vascular
      remodeling leads to focal loss of capillaries. Current treatments for HHT1
      include antiangiogenic therapies. Interestingly, a circulating form of endoglin
      (also known as soluble endoglin, sEng), proteolytically released from the
      membrane-bound protein and displaying antiangiogenic activity, has been described
      in several endothelial-related pathological conditions. Using human and mouse
      endothelial cells, we find that sEng downregulates several pro-angiogenic and pro
      migratory proteins involved in angiogenesis. However, this effect is much reduced
      in endothelial cells that lack endogenous transmembrane endoglin, suggesting that
      the antiangiogenic activity of sEng is dependent on the presence of endogenous
      transmembrane endoglin protein. In fact, sEng partially restores the phenotype of
      endoglin-silenced endothelial cells to that of normal endothelial cells.
      Moreover, using an established neonatal retinal model of HHT1 with depleted
      endoglin in the vascular endothelium, sEng treatment decreases the number of AVMs
      and has a normalizing effect on the vascular phenotype with respect to vessel
      branching, vascular density and migration of the vascular plexus towards the
      retinal periphery. Taken together, these data show that circulating sEng can
      influence vascular development and AVMs by modulating angiogenesis, and that its
      effect on endothelial cells depends on the expression of endogenous endoglin.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 30108054
TI  - Overdiagnosis in primary care: framing the problem and finding solutions.
AB  - Overdiagnosis, is defined as the diagnosis of a condition that, if unrecognized,
      would not cause symptoms or harm a patient during his or her lifetime, and it is
      increasingly acknowledged as a consequence of screening for cancer and other
      conditions. Because preventive care is a crucial component of primary care, which
      is delivered to the broad population, overdiagnosis in primary care is an
      important problem from a public health perspective and has far reaching
      implications. The scope of overdiagnosis as a result of services delivered in
      primary care is unclear, though overdiagnosis of indolent breast, prostate,
      thyroid, and lung cancers is well described and overdiagnosis of chronic kidney
      disease, depression, and attention-deficit/hyperactivity disorder is also
      recognized. However, overdiagnosis is a known consequence of all screening and
      can be assumed to occur in many more clinical contexts. Overdiagnosis can harm
      patients by leading to overtreatment (with associated potential toxicities),
      diagnosis related anxiety or depression, and labeling, or through financial
      burden. Many entrenched factors facilitate overdiagnosis, including the growing
      use of advanced diagnostic technology, financial incentives, a medical culture
      that encourages greater use of tests and treatments, limitations in the evidence
      that obscure the understanding of diagnostic utility, use of non-beneficial
      screening tests, and the broadening of disease definitions. Efforts to reduce
      overdiagnosis are hindered by physicians' and patients' lack of awareness of the
      problem and by confusion about terminology, with overdiagnosis often conflated
      with related concepts. Clarity of terminology would facilitate physicians'
      understanding of the problem and the growth in evidence regarding its prevalence
      and downstream consequences in primary care. It is hoped that international
      coordination regarding diagnostic standards for disease definitions will also
      help minimize overdiagnosis in the future.

PMID- 30108053
TI  - MIWI2 targets RNAs transcribed from piRNA-dependent regions to drive DNA
      methylation in mouse prospermatogonia.
AB  - Argonaute/Piwi proteins can regulate gene expression via RNA degradation and
      translational regulation using small RNAs as guides. They also promote the
      establishment of suppressive epigenetic marks on repeat sequences in diverse
      organisms. In mice, the nuclear Piwi protein MIWI2 and Piwi-interacting RNAs
      (piRNAs) are required for DNA methylation of retrotransposon sequences and some
      other sequences. However, its underlying molecular mechanisms remain unclear.
      Here, we show that piRNA-dependent regions are transcribed at the stage when
      piRNA-mediated DNA methylation takes place. MIWI2 specifically interacts with
      RNAs from these regions. In addition, we generated mice with deletion of a
      retrotransposon sequence either in a representative piRNA-dependent region or in
      a piRNA cluster. Both deleted regions were required for the establishment of DNA
      methylation of the piRNA-dependent region, indicating that piRNAs determine the
      target specificity of MIWI2-mediated DNA methylation. Our results indicate that
      MIWI2 affects the chromatin state through base-pairing between piRNAs and nascent
      RNAs, as observed in other organisms possessing small RNA-mediated epigenetic
      regulation.

PMID- 30108056
TI  - Light smoking confers up to half the amount of the cardiovascular risk associated
      with smoking a pack of cigarettes a day.

PMID- 30108057
TI  - Erenumab is effective in reducing migraine frequency and improving physical
      functioning.

PMID- 30108058
TI  - More than 2 billion pairs of eyeballs: Why aren't you sharing medical knowledge
      on Wikipedia?

PMID- 30108059
TI  - Meta-analysis suggests that metformin may reduce pre-eclampsia compared with
      insulin use during pregnancy.

PMID- 30108061
TI  - US dietary guidelines: is saturated fat a nutrient of concern?
AB  - US public health dietary advice was announced by the Select Committee on
      Nutrition and Human needs in 1977 and was followed by UK public health dietary
      advice issued by the National Advisory Committee on Nutritional Education in
      1983. Dietary recommendations in both cases focused on reducing dietary fat
      intake; specifically to (i) reduce overall fat consumption to 30% of total energy
      intake and (ii) reduce saturated fat consumption to 10% of total energy intake.
      The recommendations were an attempt to address the incidence of coronary heart
      disease. These guidelines have been reiterated in the Dietary Guidelines for
      Americans since the first edition in 1980. The most recent edition has positioned
      the total fat guideline with the use of 'Acceptable Macronutrient Distribution
      Ranges'. The range given for total fat is 20%-35% and the AMDR for saturated fat
      is given as <10%-both as a percentage of daily calorie intake. In February 2018,
      the Center for Nutrition Policy and Promotion announced 'The US Departments of
      Agriculture and Health and Human Services currently are asking for public
      comments on topics and supporting scientific questions to inform our development
      of the 2020-2025 Dietary Guidelines for Americans'. Public comments were invited
      on a number of nutritional topics. The question asked about saturated fats was:
      'What is the relationship between saturated fat consumption (types and amounts)
      during adulthood and risk of cardiovascular disease?' This article is a response
      to that question.

PMID- 30108060
TI  - A Drosophila model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a
      mechanism linking mitochondrial citrate export with oncometabolite accumulation.
AB  - The enantiomers of 2-hydroxyglutarate (2HG) are potent regulators of metabolism,
      chromatin modifications and cell fate decisions. Although these compounds are
      associated with tumor metabolism and commonly referred to as oncometabolites,
      both D- and L-2HG are also synthesized by healthy cells and likely serve
      endogenous functions. The metabolic mechanisms that control 2HG metabolism in
      vivo are poorly understood. One clue towards how cells regulate 2HG levels has
      emerged from an inborn error of metabolism known as combined D- and L-2HG
      aciduria (D-/L-2HGA), which results in elevated D- and L-2HG accumulation.
      Because this disorder is caused by mutations in the mitochondrial citrate
      transporter (CIC), citrate must somehow govern 2HG metabolism in healthy cells.
      The mechanism linking citrate and 2HG, however, remains unknown. Here, we use the
      fruit fly Drosophila melanogaster to elucidate a metabolic link between citrate
      transport and L-2HG accumulation. Our study reveals that the Drosophila gene
      scheggia (sea), which encodes the fly CIC homolog, dampens glycolytic flux and
      restricts L-2HG accumulation. Moreover, we find that sea mutants accumulate
      excess L-2HG owing to elevated lactate production, which inhibits L-2HG
      degradation by interfering with L-2HG dehydrogenase activity. This unexpected
      result demonstrates that citrate indirectly regulates L-2HG stability and reveals
      a feedback mechanism that coordinates L-2HG metabolism with glycolysis and the
      tricarboxylic acid cycle. Finally, our study also suggests a potential strategy
      for preventing L-2HG accumulation in human patients with CIC deficiency.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 30108062
TI  - Overuse injuries are prevalent in children's competitive football: a prospective
      study using the OSTRC Overuse Injury Questionnaire.
AB  - OBJECTIVES: To investigate the prevalence and burden of overuse injuries in
      children's football as well as player characteristics and their association with
      overuse injury risk. METHODS: This investigation is based on the control arm (10
      clubs) of a randomised controlled trial investigating prevention of injuries in
      youth football. We conducted a prospective 20-week follow-up study on overuse
      injuries among Finnish football players (n=733, aged 9-14 years). Each week, we
      sent a text message to players' parents to ask if the player had sustained any
      injury during the past week. Players with overuse problem were interviewed over
      the phone using an overuse injury questionnaire. The main outcome measures were
      prevalence of all overuse injuries and substantial overuse injuries (those
      leading to moderate or severe reductions in participation or performance) and
      injury severity. RESULTS: The average response rate was 95%. In total, 343
      players (46.8%) reported an overuse problem while in the study. The average
      weekly prevalence of all overuse problems and substantial overuse problems was
      12.8% and 6.0%, respectively. Injuries affecting the knee had the highest weekly
      prevalence (5.7% and 2.4% for all and substantial knee problems, respectively).
      Girls had a higher likelihood of knee problems (OR 2.70; 95% CI 1.69 to 4.17),
      whereas boys had a higher likelihood of heel problems (OR 2.82; 95% CI 1.07 to
      7.44). The likelihood of reporting an overuse problem increased with age (OR
      1.21; 95% CI 1.00 to 1.47). CONCLUSION: Overuse injuries are prevalent in
      children's competitive football. Knee overuse injuries represent the greatest
      burden on participation and performance. TRIAL REGISTRATION NUMBER:
      ISRCTN14046021.

PMID- 30108055
TI  - Mechanisms for stalled replication fork stabilization: new targets for synthetic
      lethality strategies in cancer treatments.
AB  - Timely and faithful duplication of the entire genome depends on completion of
      replication. Replication forks frequently encounter obstacles that may cause
      genotoxic fork stalling. Nevertheless, failure to complete replication rarely
      occurs under normal conditions, which is attributed to an intricate network of
      proteins that serves to stabilize, repair and restart stalled forks. Indeed, many
      of the components in this network are encoded by tumour suppressor genes, and
      their loss of function by mutation or deletion generates genomic instability, a
      hallmark of cancer. Paradoxically, the same fork-protective network also confers
      resistance of cancer cells to chemotherapeutic drugs that induce high-level
      replication stress. Here, we review the mechanisms and major pathways rescuing
      stalled replication forks, with a focus on fork stabilization preventing fork
      collapse. A coherent understanding of how cells protect their replication forks
      will not only provide insight into how cells maintain genome stability, but also
      unravel potential therapeutic targets for cancers refractory to conventional
      chemotherapies.

PMID- 30108063
TI  - MRI for degenerative meniscal lesions: cease and desist! A three-step action
      plan.

PMID- 30108064
TI  - Next-generation sequencing-based posttransplant monitoring of acute myeloid
      leukemia identifies patients at high risk of relapse.
AB  - Next-generation sequencing (NGS) has been applied to define clinically relevant
      somatic mutations and classify subtypes in acute myeloid leukemia (AML).
      Persistent allelic burden after chemotherapy is associated with higher relapse
      incidence, but presence of allelic burden in AML patients after receiving
      allogeneic hematopoietic cell transplantation (HCT) has not been examined
      longitudinally. As such, we aimed to assess the feasibility of NGS in monitoring
      AML patients receiving HCT. Using a targeted gene panel, we performed NGS in 104
      AML patients receiving HCT using samples collected at diagnosis, pre-HCT, and
      post-HCT at day 21 (post-HCTD21). NGS detected 256 mutations in 90 of 104
      patients at diagnosis, which showed stepwise clearances after chemotherapy and
      HCT. In a subset of patients, mutations were still detectable pre-HCT and post
      HCT. Most post-HCT mutations originate from mutations initially detected at
      diagnosis. Post-HCTD21 allelic burdens in relapsed patients were higher than in
      nonrelapsed patients. Post-HCTD21 mutations in relapsed patients all expanded at
      relapse. Assessment of variant allele frequency (VAF) revealed that overall VAF
      post-HCTD21 (VAF0.2%-post-HCTD21) is associated with an increased risk of relapse
      (56.2% vs 16.0% at 3 years; P < .001) and worse overall survival (OS; 36.5% vs
      67.0% at 3 years; P = .006). Multivariate analyses confirmed that VAF0.2%-post
      HCTD21 is an adverse prognostic factor for OS (hazard ratio [HR], 3.07; P = .003)
      and relapse incidence (HR, 4.75; P < .001), independent of the revised European
      LeukemiaNet risk groups. Overall, current study demonstrates that NGS-based
      posttransplant monitoring in AML patients is feasible and can distinguish high
      risk patients for relapse.

PMID- 30108065
TI  - Treatment of AL amyloidosis with bendamustine: a study of 122 patients.

PMID- 30108066
TI  - Proton therapy for adults with mediastinal lymphomas: the International Lymphoma
      Radiation Oncology Group guidelines.
AB  - Among adult lymphoma survivors, radiation treatment techniques that increase the
      excess radiation dose to organs at risk (OARs) put patients at risk for increased
      side effects, especially late toxicities. Minimizing radiation to OARs in adults
      patients with Hodgkin and non-Hodgkin lymphomas involving the mediastinum is the
      deciding factor for the choice of treatment modality. Proton therapy may help to
      reduce the radiation dose to the OARs and reduce toxicities, especially the risks
      for cardiac morbidity and second cancers. Because proton therapy may have some
      disadvantages, identifying the patients and the circumstances that may benefit
      the most from proton therapy is important. We present modern guidelines to
      identify adult lymphoma patients who may derive the greatest benefit from proton
      therapy, along with an analysis of the advantages and disadvantages of proton
      treatment.

PMID- 30108067
TI  - Assessment of family medicine residents.

PMID- 30108068
TI  - ?

PMID- 30108069
TI  - Negotiating "unnecessary": Microclinical, macropolitical, and coproduction
      approaches to defining necessity in care.

PMID- 30108070
TI  - ?

PMID- 30108071
TI  - Approach to developmental disabilities in newcomer families.
AB  - OBJECTIVE: To provide a framework for primary care providers to approach
      developmental disabilities in both refugee and nonrefugee immigrant populations.
      SOURCES OF INFORMATION: Ovid MEDLINE was searched from January 2005 to February
      2017 using subject headings developmental disability, developmental delay,
      refugee, and immigrant for relevant English-language articles. Most of the
      content and recommendations in this review are derived from the Canadian
      Paediatric Society's Caring for Kids New to Canada website. MAIN MESSAGE: As
      family physicians, it can be daunting to care for newcomer families who arrive
      without previous developmental disability or delay screening and diagnoses.
      Disruption to families and education, decreased health literacy, witnessed
      traumatic events, and culturally specific barriers can affect the presentation of
      developmental concerns among refugees and immigrants. Surveillance and screening
      for developmental concerns in a culturally sensitive manner using evidence-based
      tools are cornerstones of early intervention. CONCLUSION: For refugees in
      particular, in light of the inequities they have faced before migration and
      during their migration trajectory, screening for developmental disabilities and
      intervening provides an opportunity to help achieve equitable outcomes for
      refugee children and optimize their health and well-being.

PMID- 30108073
TI  - Constriction band syndrome in a healthy full-term newborn.

PMID- 30108072
TI  - Conservative therapy for appendicitis in children.
AB  - Question A 10-year-old girl who was seen in my office last week with acute-onset
      abdominal pain and fever was referred to an emergency department, was diagnosed
      with appendicitis, and was treated conservatively with antibiotics, without
      surgery. Has the paradigm for treating appendicitis changed, and which is the
      preferred treatment of appendicitis in children: antibiotics or
      appendectomy?Answer For more than 100 years, surgical management was the
      principal treatment of acute appendicitis. Potential adverse events associated
      with appendectomy include bleeding, surgical site infection, and ileus, as well
      as stress for children and their parents. The option of treating appendicitis
      with antibiotics has been known for decades, which has led to consideration of
      antibiotics alone as a therapeutic alternative to surgery for uncomplicated
      appendicitis. While there is a reasonable body of evidence in support of this
      practice in adults, the accumulation of evidence of the safety and effectiveness
      of non-operative management in children is ongoing. Large studies are still
      needed, and those are being conducted at this time, with results expected in the
      next few years.

PMID- 30108074
TI  - Choosing Wisely Canada recommendations.

PMID- 30108075
TI  - Inhaled isopropyl alcohol for nausea and vomiting in the emergency department.

PMID- 30108076
TI  - Forearm volar slab splint: Casting Immobilization Series for Primary Care.

PMID- 30108077
TI  - Tapering opioids using motivational interviewing.

PMID- 30108079
TI  - Finishing strong: A story experienced and a story observed.

PMID- 30108078
TI  - Predictors of rural family medicine practice in Canada.
AB  - OBJECTIVE: To examine the attributes of Canadian medical students at
      matriculation that predicted later practice in a rural location, with the goal of
      enhancing evidence-based approaches to increasing the numbers of rural family
      physicians. DESIGN: Demographic, attitudinal, and career choice data were
      collected from medical students at matriculation. Students were followed
      prospectively, and these data were linked to postresidency practice location.
      SETTING: Eight Canadian medical schools. PARTICIPANTS: Study participants were 15
      classes of medical students entering medical school between 2002 and 2004. MAIN
      OUTCOME MEASURES: Backward stepwise logistic regression analysis was used to
      identify the entry characteristics that predicted postresidency practice as a
      rural family physician. RESULTS: Data from 1542 students were analyzed. A strong
      association was found between career interest in rural family medicine at entry
      into medical school and postresidency rural practice as a family physician.
      Logistic regression analysis that did not include entry career interest found
      older age, being in a relationship, having completed school in a rural community,
      having a societal orientation, and expressing a desire for a varied scope of
      practice to be predictive of practising in a rural location. When entry career
      interest in a rural setting was included in the multivariate model, only this
      variable and older age predicted postresidency rural family practice. CONCLUSION:
      This study identified a number of demographic and attitudinal variables at
      medical school entry that predict postresidency practice in a rural setting.
      These results suggest multiple potential areas where the pipeline to rural family
      practice can be further supported in order to address the shortage of rural
      family physicians.

PMID- 30108080
TI  - Abortion remains absent from family medicine training in Canada.

PMID- 30108081
TI  - New-in-practice physician voices.

PMID- 30108082
TI  - Recruiting physicians to practise in rural communities.

PMID- 30108083
TI  - ?

PMID- 30108084
TI  - ?

PMID- 30108085
TI  - The urgency of creating a primary care CIHR institute.

PMID- 30108086
TI  - ?

PMID- 30108087
TI  - ?

PMID- 30108088
TI  - ?

PMID- 30108089
TI  - Team-based comanagement of diabetes in rural primary care.
AB  - OBJECTIVE: To explore clinical indicators among patients with diabetes in
      southern Alberta and assess changes over time, and to compare patients with
      diabetes attending a reference clinic (RC), which had adapted its service model
      to address the specific needs of the patient population, with patients with
      diabetes attending comparison clinics (CCs) in the same region. DESIGN: Analysis
      of longitudinal data from the Canadian Primary Care Sentinel Surveillance Network
      (CPCSSN). SETTING: Rural southern Alberta. PARTICIPANTS: A community-based family
      medicine clinic and the 6 other CPCSSN clinics in the same region at the time of
      the study. MAIN OUTCOME MEASURES: A range of data elements from patients with
      diabetes within the RC, as well as from patients with diabetes from the CCs, were
      analyzed by CPCSSN to compare rates of comorbidity and mean body mass index,
      hemoglobin A1c levels, and blood pressure, as well as service use and measurement
      frequency. Rate of change per year was modeled longitudinally for each of the
      outcomes. RESULTS: The RC had higher proportions of patients with comorbid
      conditions and a consistently higher mean body mass index. Mean HbA1c levels
      varied minimally between the RC and CCs, with both sets worsening slightly.
      However, the rate of worsening among patients with diabetes in the RC was found
      to be significantly greater (P < .05) than for those in the CCs. Blood pressure
      also varied minimally between the RC and the CCs, with both sets improving;
      however, the RC had a significantly greater (P < .001) rate of improvement than
      the CCs did. Finally, a greater proportion of patients in the RC had complete
      data for these 3 outcome measures, and RC patients made a greater number of
      clinic visits compared with the CC patients (P < .001). CONCLUSION: This study
      describes a team-based comanagement organizational model and might provide useful
      commentary about organizational effectiveness in primary care. Although
      improvement in health outcomes cannot be directly attributed to any specific
      change in clinic organization, some statistically and likely clinically
      significant benefit was found associated with the service model of the RC in a
      relatively medically and socially challenged patient population and in a
      conservative evaluative design.

PMID- 30108092
TI  - ?

PMID- 30108091
TI  - ?

PMID- 30108090
TI  - Low-acuity presentations to the emergency department: Reasons for and access to
      other health care providers before presentation.
AB  - OBJECTIVE: To describe the demographic characteristics of patients who present to
      the emergency department (ED) for low-acuity issues and to explore their self
      reported contact with other sources of primary health care before presenting to
      the ED. DESIGN: Survey distributed in the ED waiting room. SETTING: A high-volume
      ED in Vancouver, BC. PARTICIPANTS: A total of 232 respondents aged 18 years or
      older in the ED waiting room. MAIN OUTCOME MEASURES: Actions taken to seek health
      care for the current issue before presenting to the ED and predictors of first
      seeking nonurgent care. RESULTS: Of the 398 people approached, 232 (58.3%) people
      completed the survey. Exactly half (95% CI 43.6% to 56.4%) sought alternative
      care before presenting to the ED. Predictors for having sought alternative care
      included illness presentation and longer symptom duration, while injury
      presentation and work-related presentation were associated with not seeking
      alternative care. Most participants (162 patients, 87.6%) believed that the ED
      was the most appropriate place for them to receive care for their problem, while
      only 87 (45.3%) believed that an adjacent primary care clinic would be an
      acceptable alternative. CONCLUSION: Many patients do attempt to seek alternative
      care before presenting to the ED with low acuity issues. Most patients believe
      that the ED is the best place for them to receive care and are uncertain about
      using a primary care alternative. Further research is needed to explore barriers
      and motivators patients face in their decisions to seek care, as well as
      potential patient education methods to improve appropriate ED use.

PMID- 30108093
TI  - Active cushing syndrome patients have increased ectopic fat deposition and bone
      marrow fat content compared to cured patients and healthy subjects: a pilot 1H
      MRS study.
AB  - OBJECTIVE: Glucocorticoid excess is one of the most important causes of bone
      disorders. Bone marrow fat (BMF) has been identified as a l new mediator of bone
      metabolism. Cushing syndrome (CS), is a main regulator of adipose tissue
      distribution but its impact on BMF is unknown. The objective of the study was to
      evaluate the effect of chronic hypercortisolism on BMF. DESIGN: This was a cross
      sectional study. Seventeen active and seventeen cured ACTH-dependent CS patients
      along with seventeen controls (matched with the active group for age and sex)
      were included. METHODS: the BMF content of the femoral neck and L3 vertebrae were
      measured by 1H-MRS on a 3-Tesla wide-bore magnet. BMD was evaluated in patients
      using dual-energy X-ray absorptiometry. RESULTS: Active CS patients had higher
      BMF content both in the femur (82.5+/-2.6%) and vertebrae (70.1+/-5.1%) compared
      to the controls (70.8+/-3.6%, p=0.013 and 49.0+/-3.7% p=0.005, respectively). In
      cured CS patients (average remission time of 43 months), BMF content was not
      different from controls at both sites (72.3+/-2.9% (femur) and 46.7%+/-5.3%
      (L3)). BMF content was positively correlated with age, fasting plasma glucose,
      HbA1c, triglycerides and visceral adipose tissue in the whole cohort and
      negatively correlated with BMD values in the CS patients . CONCLUSIONS:
      Accumulation of BMF is induced by hypercortisolism. In remission patients BMF
      reached values of controls. Further studies are needed to determine whether this
      increase in marrow adiposity in CS is associated with bone loss.

PMID- 30108094
TI  - Reduced Slow-Wave Sleep and Altered Diurnal Cortisol Rhythms in Patients with
      Addison's Disease.
AB  - OBJECTIVES: Cortisol plays a key role in initiating and maintaining different
      sleep stages. Patients with Addison's disease (AD) frequently report disrupted
      sleep, and their hydrocortisone medication regimes do not restore the natural
      diurnal rhythm of cortisol. However, few studies have investigated relations
      between sleep quality, especially as measured by polysomnographic equipment, and
      night-time cortisol concentrations in patients with AD. METHODS: We used sleep
      adapted EEG to monitor a full night of sleep in 7 patients with AD and 7 healthy
      controls. We sampled salivary cortisol before bedtime, at midnight, upon
      awakening, and at 30-minutes post-waking. RESULTS: Controls had lower cortisol
      concentrations than patients before bedtime and at midnight. During the second
      half of the night, patient cortisol concentrations declined steeply, while
      control concentrations increased steadily. Whereas most controls experienced a
      positive cortisol awakening response, all patients experienced a decrease in
      cortisol concentrations from waking to 30-minutes post-waking (P = .003).
      Patients experienced significantly lower proportions of slow-wave sleep (SWS; P =
      .001), which was associated with elevated night-time cortisol concentrations.
      CONCLUSION: Overall, these results suggest that patients with AD demonstrate
      different patterns of night-time cortisol concentrations to healthy controls, and
      that relatively elevated concentrations are associated with a reduction of SWS.
      These hormonal and sleep architectural aberrations may disrupt the routine sleep
      dependent processes of memory consolidation, and hence may explain, at least
      partially, the memory impairments often experienced by patients with AD.

PMID- 30108095
TI  - Determinants for Participation in Human Papillomavirus Self-Sampling among
      Nonattenders to Cervical Cancer Screening in Denmark.
AB  - Background: Offering human papillomavirus-based self-sampling to nonparticipants
      in routine cervical cancer screening can increase screening participation.
      However, little is known about characteristics of women who accept self-sampling.
      In this population-based study, we investigated determinants for participation in
      self-sampling among Danish nonattenders to routine cervical cancer
      screening.Methods: During 2014 to 2015, a random sample of screening
      nonparticipants ages 27 to 65 years living in the Capital Region of Denmark were
      invited for self-sampling. Of 21,314 eligible women, 4,743 participated in self
      sampling. Information on sociodemographic characteristics and mental and physical
      health of all the women was obtained from nationwide registries, and 3,707 women
      completed a questionnaire on lifestyle, sexual behavior, and reasons for
      nonparticipation in routine screening. We used logistic regression to estimate
      ORs for participation in self-sampling, crude, and adjusted for sociodemographic
      characteristics.Results: Basic education [ORadjusted = 0.79; 95% confidence
      interval (CI), 0.72-0.88], low income (ORadjusted = 0.66; 95% CI, 0.59-0.73),
      origin from a nonwestern country (ORadjusted = 0.43; 95% CI, 0.38-0.48), and
      being unmarried (ORadjusted = 0.66; 95% CI, 0.61-0.72) were associated with lower
      self-sampling participation. Long-term unscreened women (ORadjusted = 0.49; 95%
      CI, 0.45-0.53), women with prior schizophrenia or other psychoses (ORadjusted =
      0.62; 95% CI, 0.48-0.80), women with poor self-perceived health (ORadjusted =
      0.42; 95% CI, 0.25-0.69), and women who perceived screening as unnecessary
      (ORadjusted = 0.54; 95% CI, 0.37-0.80) or irrelevant (ORadjusted = 0.81; 95% CI,
      0.78-0.96) were less likely to self-sample.Conclusions: Certain population
      groups, including women with low socioeconomic position or of nonwestern origin,
      were less likely to participate in self-sampling.Impact: Targeted approaches may
      be needed to increase screening participation in these groups. Cancer Epidemiol
      Biomarkers Prev; 27(11); 1342-51. (c)2018 AACR.

PMID- 30108096
TI  - Evolutionary-Concordance Lifestyle and Diet and Mediterranean Diet Pattern Scores
      and Risk of Incident Colorectal Cancer in Iowa Women.
AB  - Background: Whereas diet and lifestyle are strongly implicated in the etiology of
      colorectal cancer, single exposures generally are weakly and inconsistently
      associated with the disease. Exposure patterns may be more helpful for
      investigating diet and lifestyle-colorectal cancer associations. Evolutionary
      concordance diet and Mediterranean diet pattern scores were previously found to
      be inversely associated with colorectal adenoma.Methods: To investigate
      associations of these diet scores and an evolutionary-concordance lifestyle score
      (comprising smoking status, physical activity, and body mass index) with incident
      colorectal cancer, we analyzed data from the prospective Iowa Women's Health
      Study. Diet and lifestyle scores were calculated for each participant and
      categorized into quintiles, and associations estimated using Cox proportional
      hazards models.Results: Of the 35,221 55- to 69-year-old cancer-free women at
      baseline, 1,731 developed colorectal cancer during follow-up. The multivariable
      adjusted HR comparing persons in the highest relative to the lowest quintile of
      the lifestyle score was 0.66 (95% confidence interval, 0.56-0.78; P trend <
      0.01). Although the estimated associations of the evolutionary-concordance diet
      and Mediterranean diet scores alone with colorectal cancer were null, relative to
      those in the lowest tertiles of both the evolutionary-concordance diet and
      lifestyle scores, those in the highest tertiles of both scores were at the lowest
      risk (P interaction < 0.01).Conclusions: Our findings suggest that a more
      evolutionary-concordant lifestyle, alone and in interaction with a more
      evolutionary-concordant diet pattern, may be inversely associated with colorectal
      cancer risk.Impact: These results support further investigation of colorectal
      cancer etiology using evolutionary-concordance dietary and lifestyle pattern
      scores. Cancer Epidemiol Biomarkers Prev; 27(10); 1195-202. (c)2018 AACR.

PMID- 30108098
TI  - Effects of Exercise and Cardiorespiratory Fitness on Estrogen Metabolism in
      Postmenopausal Women.
AB  - BACKGROUND: Lowering endogenous estrogen levels is one mechanism whereby physical
      activity may lower postmenopausal breast cancer risk. Several prospective studies
      have suggested that increased 2-hydroxylation of estrogens may also reduce
      postmenopausal breast cancer risk, but whether or not exercise alters estrogen
      metabolism through this mechanism is unclear. METHODS: We measured total
      circulating concentrations of parent estrogens (estrone and estradiol) and 13
      estrogen metabolites, including glucuronidated, sulfated, and unconjugated forms,
      by stable isotope dilution LC/MS-MS in 153 postmenopausal women randomized to 12
      months of moderate-to-vigorous exercise and 153 controls. We also explored
      associations with cardiorespiratory fitness measured by treadmill. RESULTS:
      Although women randomized to exercise averaged 178 minutes/week of exercise over
      12 months, their cardiorespiratory fitness was 13% greater than controls at 12
      months (P = 0.0001), and total estradiol was reduced by 10% (P = 0.04); there
      were no statistically significant effects of exercise on circulating
      concentrations of estrogen metabolites in the 2-, 4-, or 16-pathways, or on the 2
      pathway/parent estrogens ratio. However, we observed a statistically significant
      association between increased fitness and reduced concentration of 2-pathway
      metabolites (P < 0.05). CONCLUSIONS: We found no evidence that 12 months of
      moderate-to-vigorous exercise or increased fitness changed estrogen metabolism in
      a way that might reduce breast cancer risk. IMPACT: The protective effect of
      exercise on postmenopausal breast cancer is unlikely to be mediated by changes in
      estrogen metabolism.

PMID- 30108097
TI  - A Prospective Study of Aspirin Use and Prostate Cancer Risk by TMPRSS2:ERG
      Status.
AB  - Background: In a case-control study, aspirin use was associated with a lower risk
      of a common prostate cancer molecular subtype, the TMPRSS2:ERG gene fusion. We
      sought to validate this finding in a prospective cohort.Methods: In the Health
      Professionals Follow-up Study, 49,395 men reported on aspirin use on biennial
      questionnaires and were followed for prostate cancer incidence over 23 years.
      TMPRSS2:ERG status was assessed by IHC for presence of ERG on archival tumor
      specimens for 912 patients with prostate cancer, of whom 48% were ERG
      positive.Results: In multivariable models, we found no association between
      regular use of aspirin and risk of ERG-positive prostate cancer (HR, 1.02; 95%
      confidence interval, 0.85-1.23), nor any association with duration or frequency
      of aspirin use. In restricting to cases with either high Gleason grade or
      advanced stage disease, there remained no association with aspirin
      use.Conclusions: Data from this prospective study with repeated assessments of
      aspirin use do not support the hypothesis that aspirin use is associated with a
      lower risk of ERG-positive prostate cancer.Impact: Aspirin use is unlikely to
      lower the risk of this common molecular subtype of prostate cancer. However,
      there is emerging data supporting the role of other lifestyle and genetic factors
      underlying the development of the TMPRSS2:ERG fusion. Cancer Epidemiol Biomarkers
      Prev; 27(10); 1231-3. (c)2018 AACR.

PMID- 30108100
TI  - Impacts of Neighborhood Characteristics on Treatment and Outcomes in Women with
      Ductal Carcinoma In Situ of the Breast.
AB  - Background: This study examines associations of neighborhood characteristics with
      treatment and outcomes of ductal carcinoma in situ (DCIS) of the breast.Methods:
      From the Missouri Cancer Registry, we identified 9,195 women with DCIS diagnosed
      between 1996 and 2011. A composite index using U.S. Census data and American
      Community Survey data was developed to assess census tract-level socioeconomic
      deprivation, and rural-urban commuting area codes were used to define rural
      census tracts. ORs and 95% confidence intervals (CIs) of the treatment were
      estimated using logistic regression. Hazard ratios (HRs) of DCIS outcomes were
      estimated using Cox proportional hazards regression.Results: Women in the most
      socioeconomically deprived census tracts were more likely than those in the least
      deprived to have mastectomy (OR = 1.44; 95% CI, 1.25-1.66; P trend < 0.0001), no
      surgery (OR = 1.54; 95% CI, 1.02-2.30; P trend = 0.04), no radiotherapy post
      breast conserving surgery (OR = 1.90; 95% CI, 1.56-2.31; P trend<0.0001), delayed
      radiotherapy (OR = 1.26; 95% CI, 1.01-1.57; P trend = 0.02), and ipsilateral
      breast tumors (HR = 1.59; 95% CI, 1.07-2.38; P trend = 0.03). There was no
      significant difference in risk of contralateral breast tumors. Compared with
      urban women, rural women had significantly higher odds of underutilization of
      radiotherapy (OR = 1.29; 95% CI, 1.08-1.53). Rural locations were not associated
      with risk of ipsilateral or contralateral breast tumors.Conclusions: Neighborhood
      socioeconomic deprivation was associated with higher risks of suboptimal
      treatment and ipsilateral breast tumors. While DCIS treatment significantly
      varied by rural/urban locations, we did not observe any statistically significant
      rural-urban differences in risks of second breast tumors.Impact: Neighborhood
      attributes may affect treatment and outcomes of patients with DCIS. Cancer
      Epidemiol Biomarkers Prev; 27(11); 1298-306. (c)2018 AACR.

PMID- 30108101
TI  - EMA scales back transparency initiatives because of workload.

PMID- 30108099
TI  - Tristetraprolin Is a Prognostic Biomarker for Poor Outcomes among Patients with
      Low-Grade Prostate Cancer.
AB  - Background: We studied the utility of the tumor suppressor Tristetraprolin (TTP,
      ZFP36) as a clinically relevant biomarker of aggressive disease in prostate
      cancer patients after radical prostatectomy (RP).Methods: TTP RNA expression was
      measured in an RP cohort of patients treated at Moffitt Cancer Center (MCC) and
      obtained from six publically available RP datasets with biochemical recurrence
      (BCR; total n = 1,394) and/or metastatic outcome data (total n = 1,222). TTP
      protein expression was measured by immunohistochemistry in a tissue microarray of
      153 MCC RP samples. The time to BCR or metastasis based on TTP RNA or protein
      levels was calculated using the Kaplan-Meier analysis. Univariable and
      multivariable Cox proportional hazard models were performed on multiple cohorts
      to evaluate if TTP is a clinically relevant biomarker and to assess if TTP
      improves upon the Cancer of the Prostate Risk Assessment postsurgical (CAPRA-S)
      score for predicting clinical outcomes.Results: In all of the RP patient cohorts,
      prostate cancer with low TTP RNA or protein levels had decreased time to BCR or
      metastasis versus TTP-high tumors. Further, the decreased time to BCR in TTP-low
      prostate cancer was more pronounced in low-grade tumors. Finally, pooled survival
      analysis suggests that TTP RNA expression provides independent information beyond
      CAPRA-S to predict BCR.Conclusions: TTP is a promising prostate cancer biomarker
      for predicting which RP patients will have poor outcomes, especially for low
      grade prostate cancer patients.Impact: This study suggests that TTP RNA
      expression can be used to enhance the accuracy of CAPRA-S to predict outcomes in
      patients treated with RP. Cancer Epidemiol Biomarkers Prev; 27(11); 1376-83.
      (c)2018 AACR.

PMID- 30108102
TI  - Kub5-Hera RPRD1B Deficiency Promotes "BRCAness" and Vulnerability to PARP
      Inhibition in BRCA-proficient Breast Cancers.
AB  - Purpose: Identification of novel strategies to expand the use of PARP inhibitors
      beyond BRCA deficiency is of great interest in personalized medicine. Here, we
      investigated the unannotated role of Kub5-HeraRPRD1B (K-H) in homologous
      recombination (HR) repair and its potential clinical significance in targeted
      cancer therapy.Experimental Design: Functional characterization of K-H
      alterations on HR repair of double-strand breaks (DSB) were assessed by targeted
      gene silencing, plasmid reporter assays, immunofluorescence, and Western blots.
      Cell survival with PARP inhibitors was evaluated through colony-forming assays
      and statistically analyzed for correlation with K-H expression in various BRCA1/2
      nonmutated breast cancers. Gene expression microarray/qPCR analyses, chromatin
      immunoprecipitation, and rescue experiments were used to investigate molecular
      mechanisms of action.Results: K-H expression loss correlates with rucaparib LD50
      values in a panel of BRCA1/2 nonmutated breast cancers. Mechanistically, K-H
      depletion promotes BRCAness, where extensive upregulation of PARP1 activity was
      required for the survival of breast cancer cells. PARP inhibition in these cells
      led to synthetic lethality that was rescued by wild-type K-H reexpression, but
      not by a mutant K-H (p.R106A) that weakly binds RNAPII. K-H mediates HR by
      facilitating recruitment of RNAPII to the promoter region of a critical DNA
      damage response and repair effector, cyclin-dependent kinase 1
      (CDK1).Conclusions: Cancer cells with low K-H expression may have exploitable
      BRCAness properties that greatly expand the use of PARP inhibitors beyond BRCA
      mutations. Our results suggest that aberrant K-H alterations may have vital
      translational implications in cellular responses/survival to DNA damage,
      carcinogenesis, and personalized medicine. Clin Cancer Res; 1-12. (c)2018 AACR.

PMID- 30108104
TI  - Validation of miR-31-3p Expression to Predict Cetuximab Efficacy When Used as
      First-Line Treatment in RAS Wild-Type Metastatic Colorectal Cancer.
AB  - Purpose: MiR-31-3p expression has been shown to be associated with response to
      anti-EGFR therapy. We investigated the predictive role of this biomarker in the
      FIRE-3 study population, including its ability to differentiate outcomes between
      patients receiving anti-EGFR and anti-VEGF therapy.Experimental Design: MiR-31-3p
      expression was measured in primary tumors obtained from 340 patients with RAS WT
      mCRC enrolled in the FIRE-3 Trial. This included 164 patients randomized to
      receive FOLFIRI plus cetuximab (FOLFIRI+Cetux) and 176 to FOLFIRI plus
      bevacizumab (FOLFIRI+Beva). Patients were divided into subgroups defined by low
      or high miR-31-3p expression using a prespecified cut-off and by treatment arm.
      Analyses were performed to assess treatment efficacy by subgroup. Overall
      survival (OS) and progression-free survival (PFS) were analyzed using Kaplan
      Meier curves and Cox regression models. Investigator-assessed objective response
      (iOR), early tumor shrinkage at 6 weeks (ETS), and centrally reviewed objective
      response (cOR) were analyzed using logistic regression models. The predictive
      value of miR-31-3p expression level was assessed through a treatment interaction
      test using multivariate models adjusted for potential confounding
      factors.Results: Low miR-31-3p expressers benefited from cetuximab compared with
      bevacizumab for PFS [HR, 0.74; 95% confidence interval (CI), 0.55-1.00; P =
      0.05], OS (HR, 0.61; 95% CI, 0.41-0.88; P < 0.01), iOR (OR, 4.0; 95% CI, 1.9-8.2;
      P < 0.01), ETS (OR, 4.0; 95% CI, 2.1-7.7; P < 0.01 and cOR (OR, 4.9; 95% CI, 2.3
      10.5; P < 0.01) in multivariate analyses. There was no difference in outcomes for
      high expressers between treatment arms. MiR-31-3p expression level was predictive
      of treatment effect for PFS (P = 0.03), OS (P = 0.05), iOR (P = 0.02), ETS (P =
      0.04), and cOR (P < 0.01).Conclusions: MiR-31-3p expression level was validated
      as a predictive biomarker of cetuximab therapy efficacy for patients with RAS WT
      mCRC. Clin Cancer Res; 1-8. (c)2018 AACR.

PMID- 30108103
TI  - Methylomic Analysis of Ovarian Cancers Identifies Tumor-Specific Alterations
      Readily Detectable in Early Precursor Lesions.
AB  - Purpose: High-grade serous ovarian carcinoma (HGSOC) typically remains
      undiagnosed until advanced stages when peritoneal dissemination has already
      occurred. Here, we sought to identify HGSOC-specific alterations in DNA
      methylation and assess their potential to provide sensitive and specific
      detection of HGSOC at its earliest stages.Experimental Design: MethylationEPIC
      genome-wide methylation analysis was performed on a discovery cohort comprising
      23 HGSOC, 37 non-HGSOC malignant, and 36 histologically unremarkable gynecologic
      tissue samples. The resulting data were processed using selective bioinformatic
      criteria to identify regions of high-confidence HGSOC-specific differential
      methylation. Quantitative methylation-specific real-time PCR (qMSP) assays were
      then developed for 8 of the top-performing regions and analytically validated in
      a cohort of 90 tissue samples. Lastly, qMSP assays were used to assess and
      compare methylation in 30 laser-capture microdissected (LCM) fallopian tube
      epithelia samples obtained from cancer-free and serous tubal intraepithelial
      carcinoma (STIC) positive women.Results: Bioinformatic selection identified 91
      regions of robust, HGSOC-specific hypermethylation, 23 of which exhibited an area
      under the receiver-operator curve (AUC) value >= 0.9 in the discovery cohort.
      Seven of 8 top-performing regions demonstrated AUC values between 0.838 and 0.968
      when analytically validated by qMSP in a 90-patient cohort. A panel of the 3 top
      performing genes (c17orf64, IRX2, and TUBB6) was able to perfectly discriminate
      HGSOC (AUC 1.0). Hypermethylation within these loci was found exclusively in LCM
      fallopian tube epithelia from women with STIC lesions, but not in cancer-free
      fallopian tubes.Conclusions: A panel of methylation biomarkers can be used to
      accurately identify HGSOC, even at precursor stages of the disease. Clin Cancer
      Res; 1-12. (c)2018 AACR.

PMID- 30108105
TI  - Biochemical and Epigenetic Insights into L-2-Hydroxyglutarate, a Potential
      Therapeutic Target in Renal Cancer.
AB  - Purpose: Elevation of L-2-hydroxylgutarate (L-2-HG) in renal cell carcinoma (RCC)
      is due in part to reduced expression of L-2-HG dehydrogenase (L2HGDH). However,
      the contribution of L-2-HG to renal carcinogenesis and insight into the
      biochemistry and targets of this small molecule remains to be
      elucidated.Experimental Design: Genetic and pharmacologic approaches to modulate
      L-2-HG levels were assessed for effects on in vitro and in vivo phenotypes.
      Metabolomics was used to dissect the biochemical mechanisms that promote L-2-HG
      accumulation in RCC cells. Transcriptomic analysis was utilized to identify
      relevant targets of L-2-HG. Finally, bioinformatic and metabolomic analyses were
      used to assess the L-2-HG/L2HGDH axis as a function of patient outcome and cancer
      progression.Results: L2HGDH suppresses both in vitro cell migration and in vivo
      tumor growth and these effects are mediated by L2HGDH's catalytic activity.
      Biochemical studies indicate that glutamine is the predominant carbon source for
      L-2-HG via the activity of malate dehydrogenase 2 (MDH2). Inhibition of the
      glutamine-MDH2 axis suppresses in vitro phenotypes in an L-2-HG-dependent manner.
      Moreover, in vivo growth of RCC cells with basal elevation of L-2-HG is
      suppressed by glutaminase inhibition. Transcriptomic and functional analyses
      demonstrate that the histone demethylase KDM6A is a target of L-2-HG in RCC.
      Finally, increased L-2-HG levels, L2HGDH copy loss, and lower L2HGDH expression
      are associated with tumor progression and/or worsened prognosis in patients with
      RCC.Conclusions: Collectively, our studies provide biochemical and mechanistic
      insight into the biology of this small molecule and provide new opportunities for
      treating L-2-HG-driven kidney cancers. Clin Cancer Res; 1-14. (c)2018 AACR.

PMID- 30108106
TI  - KMT2C Mutations in Diffuse-Type Gastric Adenocarcinoma Promote Epithelial-to
      Mesenchymal Transition.
AB  - Purpose: Lauren diffuse-type gastric adenocarcinomas (DGAs) are generally
      genomically stable. We identified lysine (K)-specific methyltransferase 2C
      (KMT2C) as a frequently mutated gene and examined its role in DGA
      progression.Experimental Design: We performed whole exome sequencing on tumor
      samples of 27 patients with DGA who underwent gastrectomy. Lysine (K)-specific
      methyltransferase 2C (KMT2C) was analyzed in DGA cell lines and in patient
      tumors.Results: KMT2C was the most frequently mutated gene (11 of 27 tumors
      [41%]). KMT2C expression by immunohistochemistry in tumors from 135 patients with
      DGA undergoing gastrectomy inversely correlated with more advanced tumor stage (P
      = 0.023) and worse overall survival (P = 0.017). KMT2C shRNA knockdown in non
      transformed HFE-145 gastric epithelial cells promoted epithelial-to-mesenchymal
      transition (EMT) as demonstrated by increased expression of EMT-related proteins
      N-cadherin and Slug. Migration and invasion in gastric epithelial cells following
      KMT2C knockdown increased by 47- to 88-fold. In the DGA cell lines MKN-45 and SNU
      668, which have lost KMT2C expression, KMT2C re-expression decreased expression
      of EMT-related proteins, reduced cell migration by 52% to 60%, and reduced cell
      invasion by 50% to 74%. Flank xenografts derived from KMT2C-expressing DGA
      organoids, compared with wild-type organoids, grew more slowly and lost their
      infiltrative leading edge. EMT can lead to the acquisition of cancer stem cell
      (CSC) phenotypes. KMT2C re-expression in DGA cell lines reduced spheroid
      formation by 77% to 78% and reversed CSC resistance to chemotherapy via promotion
      of DNA damage and apoptosis.Conclusions: KMT2C is frequently mutated in certain
      populations with DGA. KMT2C loss in DGA promotes EMT and is associated with worse
      overall survival. Clin Cancer Res; 1-14. (c)2018 AACR.

PMID- 30108107
TI  - A Clinical and Molecular Phase II Trial of Oral ENMD-2076 in Ovarian Clear Cell
      Carcinoma (OCCC): A Study of the Princess Margaret Phase II Consortium.
AB  - Purpose: Patients with recurrent ovarian clear cell carcinoma (OCCC) have limited
      effective options due to chemoresistance. A phase II study was designed to assess
      the activity of ENMD-2076, an oral multitarget kinase selective against Aurora A
      and VEGFR.Experimental Design: This multicenter phase II study included patients
      with recurrent OCCC who received prior platinum-based chemotherapy. Primary
      endpoints were objective response and 6-month progression-free survival (PFS)
      rates. Correlative analyses include ARID1A and PTEN expression by IHC and gene
      sequencing with a targeted custom capture next-generation sequencing
      panel.Results: Forty patients were enrolled with a median age of 54, of which 38
      patients were evaluable. ENMD-2076 was well tolerated with main related grade 3
      toxicities being hypertension (28%), proteinuria (10%), and diarrhea (10%). Best
      response was partial response for 3 patients (1 unconfirmed) and stable disease
      for 26 patients. The overall 6-month PFS rate was 22% and differed according to
      ARID1A expression (ARIDIA- vs. ARID1A+; 33% vs. 12%, P = 0.023). PTEN-positive
      expression was observed in 20 of 36 patients, and there was no correlation with
      outcome. Median PFS in patients with PI3KCA wild-type versus PI3KCA-mutated group
      was 5 versus 3.7 months (P = 0.049). Molecular profiling showed variants in
      PI3KCA (27%), ARID1A (26%), and TP53 (7%). The patient with the longest treatment
      duration (22 months) was PTEN wild-type, diploid PTEN with putative biallelic
      inactivation of ARID1A Conclusions: Single-agent ENMD-2076 did not meet the
      preset bar for efficacy. Loss of ARID1A correlated with better PFS on ENMD-2076
      and warrants further investigation as a potential predictive biomarker. Clin
      Cancer Res; 1-7. (c)2018 AACR.

PMID- 30108109
TI  - How ibrutinib, a B-cell malignancy drug, became an FDA-approved second-line
      therapy for steroid-resistant chronic GVHD.
AB  - Allogeneic hematopoietic stem cell transplantation (allo-SCT) is potentially
      curative for a number of hematologic conditions, both malignant and nonmalignant.
      However, its success can be limited by the development of acute and chronic graft
      versus-host disease (GVHD). Chronic GVHD (cGVHD) is the most common long-term
      complication following allo-SCT, and patients who develop this condition have
      significantly higher morbidity and mortality and significantly lower quality of
      life than patients who do not. Until recently, there were no US Food and Drug
      Administration (FDA)-approved therapies for cGVHD treatment. In this review
      article, we describe how ibrutinib was identified as potential cGVHD therapy
      based on preclinical cGVHD models and clinical studies in B-cell malignancies and
      elucidation of its mechanisms of action in cGVHD. Results from a phase 2 clinical
      trial that was designed based on National Institutes of Health Criteria for the
      grading and staging of cGVHD culminated in the FDA-approval of ibrutinib as
      second line therapy of steroid-refractory or steroid-resistant cGVHD. Results of
      ibrutinib studies in phase 3 randomized studies, for cGVHD prophylaxis and as
      first -line testing along with steroids will be especially important in selecting
      the preferred indications for ibrutinib in patients at risk for or who have
      developed cGVHD.

PMID- 30108108
TI  - Induced pluripotent stem cell-based mapping of beta-globin expression throughout
      human erythropoietic development.
AB  - Robust beta-globin expression in erythroid cells derived from induced pluripotent
      stem cells (iPSCs) increases the resolution with which red blood cell disorders
      such as sickle cell disease and beta thalassemia can be modeled in vitro. To
      better quantify efforts in augmenting beta-globin expression, we report the
      creation of a beta-globin reporter iPSC line that allows for the mapping of beta
      globin expression throughout human erythropoietic development in real time at
      single-cell resolution. Coupling this tool with single-cell RNA sequencing
      (scRNAseq) identified features that distinguish beta-globin-expressing cells and
      allowed for the dissection of the developmental and maturational statuses of iPSC
      derived erythroid lineage cells. Coexpression of embryonic, fetal, and adult
      globins in individual cells indicated that these cells correspond to a yolk sac
      erythromyeloid progenitor program of hematopoietic development, representing the
      onset of definitive erythropoiesis. Within this developmental program, scRNAseq
      analysis identified a gradient of erythroid maturation, with beta-globin
      expressing cells showing increased maturation. Compared with other cells, beta
      globin-expressing cells showed a reduction in transcripts coding for ribosomal
      proteins, increased expression of members of the ubiquitin-proteasome system
      recently identified to be involved in remodeling of the erythroid proteome, and
      upregulation of genes involved in the dynamic translational control of red blood
      cell maturation. These findings emphasize that definitively patterned iPSC
      derived erythroblasts resemble their postnatal counterparts in terms of gene
      expression and essential biological processes, confirming their potential for
      disease modeling and regenerative medicine applications.

PMID- 30108110
TI  - Severe aplastic anemia: allogeneic bone marrow transplantation as first-line
      treatment.
AB  - Treatment of severe aplastic anemia has improved significantly over the past 4
      decades. This review will summarize the key areas of progress in the use of
      allogeneic hematopoietic cell transplantation and nontransplant immunosuppressive
      therapy (IST) for the treatment of aplastic anemia and then summarize the
      recommendations for first-line treatment. Based on recent data, we argue that
      guidelines for the initial treatment of patients with newly diagnosed severe
      aplastic anemia require revision. At the time of diagnosis, before beginning
      treatment, HLA typing should be done to identify a marrow donor among family
      members or in the unrelated donor registries, and a marrow transplant should be
      considered first-line therapy. The priority order of donor source for bone marrow
      transplantation is: (1) HLA-identical sibling, (2) HLA-matched unrelated donor,
      and (3) HLA-haploidentical donor if an HLA-matched unrelated donor is not rapidly
      available. Each of these donor marrow sources may be preferable to nontransplant
      IST. We make this recommendation because of the long-term persistent risk for
      disease relapse and secondary myelodysplastic syndrome or acute myeloid leukemia
      with the use of nontransplant IST for patients with aplastic anemia. In contrast,
      marrow transplantation is associated with high cure rates of aplastic anemia and
      a relatively low risk for graft-versus-host disease, with many patients now
      living for decades without the risk for disease recurrence or the development of
      clonal disorders. Implementation of this first-line treatment strategy will
      provide patients with severe aplastic anemia the best chance of long-term disease
      free survival.

PMID- 30108111
TI  - Dichloroacetate, an inhibitor of pyruvate dehydrogenase kinases, inhibits
      platelet aggregation and arterial thrombosis.
AB  - Resting platelets rely on oxidative phosphorylation (OXPHOS) and aerobic
      glycolysis (conversion of glucose to lactate in the presence of oxygen) to
      generate adenosine triphosphate, whereas activated platelets exhibit a high level
      of aerobic glycolysis, suggesting the existence of metabolic flexibility in
      platelets. Mitochondrial pyruvate dehydrogenase kinases (PDK 1-4) play a pivotal
      role in metabolic flexibility by inhibiting pyruvate dehydrogenase complex. We
      determined whether metabolic reprogramming, diverting metabolism from aerobic
      glycolysis back to OXPHOS, would inhibit platelet function. PDKs activity in
      human and mouse platelets was inhibited with dichloroacetic acid (DCA), a potent
      inhibitor of all 4 forms of PDK. Human and mouse platelets pretreated with DCA
      exhibited decreased platelet aggregation to suboptimal doses of collagen,
      convulxin, thrombin, and adenosine diphosphate concomitant with decreased glucose
      uptake. Bioenergetics profile revealed that platelets pretreated with DCA
      exhibited decreased aerobic glycolysis in response to convulxin only.
      Furthermore, DCA inhibited ATP secretion, thromboxane A2 generation, and tyrosine
      phosphorylation of Syk and PLCgamma2 in response to collagen or convulxin in
      human and mouse platelets (P < .05 vs vehicle treated). In the flow chamber
      assay, human and mouse blood pretreated with DCA formed smaller thrombi when
      perfused over collagen for 10 minutes at an arterial shear rate of 1500 s-1 (P <
      .05 vs control). Wild-type mice pretreated with DCA were less susceptible to
      thrombosis in the FeCl3-induced carotid and laser injury-induced mesenteric
      artery thrombosis models (P < .05 vs vehicle control), without altering
      hemostasis. Targeting metabolic plasticity with DCA may be explored as a novel
      strategy to inhibit platelet function.

PMID- 30108114
TI  - Bilateral primary adrenal lymphoma successfully treated with non-CHOP
      chemotherapy regimen.
AB  - Primary bilateral non-Hodgkin's lymphoma of the adrenal gland is a rare
      presentation with <200 reported cases. We report a 70-year-old man who presented
      with vomiting and abdominal pain for 2 weeks and was subsequently diagnosed to
      have high-grade lymphoma of the adrenal glands. The patient was then started on a
      rituximab-bendamustine chemotherapy regimen. The patient tolerated treatment well
      without significant side effects. Repeat positron emission tomography CT scan
      after four cycles of chemotherapy showed complete response. The patient has
      completed six cycles of chemotherapy and is on regular follow-up with no signs of
      relapse.

PMID- 30108115
TI  - Gallbladder empyema complicating acute myeloid leukaemia in an adolescent boy.
AB  - Gallbladder (GB) empyema is an uncommon complication in acute myeloid leukaemia
      (AML). Non-specific signs and symptoms and rarity of disease in AML make it
      difficult to diagnose early. We report a case of 13-year-old boy who had AML and
      developed GB empyema in the neutropaenic period. The patient was managed with
      antibiotics, ultrasound-guided tapping and interval cholecystectomy and recovered
      well. GB empyema is a life-threatening complication which should be kept as a
      possibility while evaluating patients with neutropaenia with pain abdomen
      localised to right hypochondrium as early diagnosis and treatment can lead to
      better outcomes.

PMID- 30108116
TI  - Aneurysmal fibrous histiocytoma.
AB  - Aneurysmal fibrous histiocytoma (AFH) is a type of fibrohistiocytic tumour. We
      present a case of a patient who presented with a skin papule on the thigh region.
      Histopathological examination following total excision of the lesion revealed an
      AFH. No sign of recurrence was present 6 months after surgery.

PMID- 30108113
TI  - Comprehensive evaluation of coding region point mutations in microsatellite
      unstable colorectal cancer.
AB  - Microsatellite instability (MSI) leads to accumulation of an excessive number of
      mutations in the genome, mostly small insertions and deletions. MSI colorectal
      cancers (CRCs), however, also contain more point mutations than microsatellite
      stable (MSS) tumors, yet they have not been as comprehensively studied. To
      identify candidate driver genes affected by point mutations in MSI CRC, we ranked
      genes based on mutation significance while correcting for replication timing and
      gene expression utilizing an algorithm, MutSigCV Somatic point mutation data from
      the exome kit-targeted area from 24 exome-sequenced sporadic MSI CRCs and
      respective normals, and 12 whole-genome-sequenced sporadic MSI CRCs and
      respective normals were utilized. The top 73 genes were validated in 93
      additional MSI CRCs. The MutSigCV ranking identified several well-established MSI
      CRC driver genes and provided additional evidence for previously proposed CRC
      candidate genes as well as shortlisted genes that have to our knowledge not been
      linked to CRC before. Two genes, SMARCB1 and STK38L, were also functionally
      scrutinized, providing evidence of a tumorigenic role, for SMARCB1 mutations in
      particular.

PMID- 30108117
TI  - Epstein-Barr-positive classical Hodgkin lymphoma-associated haemophagocytic
      lymphohistocytiosis: a rare case.
AB  - Haemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition, which
      is usually triggered by autoimmune disorders, viral infections and malignancy,
      like lymphomas. We present a 60-year-old Hispanic woman with a medical history of
      hypertension and systemic lupus erythematosus presenting with fever, generalised
      weakness and shortness of breath for 3 weeks. She was hypotensive on
      presentation, and a CT scan of abdomen/chest showed multiple irregular hepatic
      and splenic hypodense lesions. A liver biopsy revealed Classical Hodgkin lymphoma
      (cHL) with positive Epstein-Barr virus (EBV) staining that was later confirmed
      with high serum EBV DNA levels. Incidentally, a liver biopsy disclosed
      haemophagocytosis in some cells. HLH-associated cHL is an uncommon condition that
      can cause severe systemic symptoms acting as the perfect mimic of septic shock,
      deviating the clinical eye toward treating with antibiotics and not addressing in
      a timely manner the real aetiology of the patient's condition.

PMID- 30108112
TI  - CEP55 is a determinant of cell fate during perturbed mitosis in breast cancer.
AB  - The centrosomal protein, CEP55, is a key regulator of cytokinesis, and its
      overexpression is linked to genomic instability, a hallmark of cancer. However,
      the mechanism by which it mediates genomic instability remains elusive. Here, we
      showed that CEP55 overexpression/knockdown impacts survival of aneuploid cells.
      Loss of CEP55 sensitizes breast cancer cells to anti-mitotic agents through
      premature CDK1/cyclin B activation and CDK1 caspase-dependent mitotic cell death.
      Further, we showed that CEP55 is a downstream effector of the MEK1/2-MYC axis.
      Blocking MEK1/2-PLK1 signaling therefore reduced outgrowth of basal-like
      syngeneic and human breast tumors in in vivo models. In conclusion, high CEP55
      levels dictate cell fate during perturbed mitosis. Forced mitotic cell death by
      blocking MEK1/2-PLK1 represents a potential therapeutic strategy for MYC-CEP55
      dependent basal-like, triple-negative breast cancers.

PMID- 30108118
TI  - Prostatitis, a rare presentation of granulomatosis with polyangiitis,
      successfully treated with rituximab and prednisone.
AB  - A previously healthy 21-year-old man presented with an 8-month history of weight
      loss, lethargy and dysuria unresponsive to empiric antibiotics and paraurethral
      drainage of a prostatic abscess. Urinalysis showed pyuria, but cultures failed to
      grow any organisms. Additionally, he developed new onset sensorineural hearing
      loss. CT of the chest showed two right-sided cavitary lesions. CT of the abdomen
      and pelvis demonstrated a prostatic abscess. A prostate biopsy demonstrated
      necrotising granulomatous prostatitis. A lung biopsy showed necrotising
      granulomatous inflammation. He was diagnosed with granulomatosis with
      polyangiitis (GPA). He was successfully treated with rituximab and prednisone. At
      6-month follow-up, he continued to be in remission with resolution of his
      symptoms. This case demonstrates a rare presentation of prostatitis as the
      presenting symptom of GPA. As far as we know, this case is the first documented
      report of rituximab and prednisone as successful therapy for prostatitis
      secondary to GPA.

PMID- 30108119
TI  - Thyroid metastasis from rectal adenocarcinoma.
AB  - The thyroid is a rare site for metastasis, occurring in 0.1% of colorectal cases.
      A 46-year-old man with rectal adenocarcinoma developed an enlarging anterior neck
      mass and increasing carcinoembryonic antigen 2 years after curative intent
      treatment. Imaging showed aggressive features with invasion of the larynx,
      trachea and oesophagus, suspicious for anaplastic thyroid carcinoma. The patient
      underwent tumour debulking with neck dissection and tracheostomy. Final
      histopathological review revealed metastatic adenocarcinoma from a colorectal
      primary. Despite chemotherapy, the patient eventually succumbed to disease
      progression and complications of his illness. This case demonstrates that
      recognising rare sites of metastasis may help clinicians effectively institute
      earlier intervention.

PMID- 30108120
TI  - Severe thromboembolic phenomenon in the setting of pseudoprogression of melanoma
      brain metastases in response to combination immunotherapy.
AB  - Approximately half of patients with metastatic melanoma develop brain metastasis
      (MBM) in their disease course. However, patients with MBM were often excluded
      from early immunotherapy trials, and therefore, the role of immunotherapy in
      these patients is less clear. We review the case of a patient with widespread
      metastatic melanoma and symptomatic brain metastases at initial diagnosis. In
      this case, we have demonstrated that it is reasonable to pursue combination
      ipilimumab and nivolumab in borderline performance status patients with extensive
      brain metastases. Additionally, this case teaches us to be vigilant for severe
      autoimmune toxicities such as severe thrombotic events in the setting of
      pseudoprogression of brain metastases. We discuss this case in the context of the
      current melanoma literature.

PMID- 30108121
TI  - Adenocarcinoma within a tailgut cyst.

PMID- 30108122
TI  - Post-traumatic aortic pseudoaneurysm causing acquired pulmonary artery stenosis.

PMID- 30108123
TI  - Aphallia: do sociocultural issues affect treatment decisions?

PMID- 30108124
TI  - Penile fracture after priapism due to sildenafil ingestion: out of frying pan
      into the fire.

PMID- 30108125
TI  - Natural killers shed attachments to kill again.
AB  - Natural killer cells target antibody-bound cells following engagement of the Fc
      receptor CD16. Srpan et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201712085) reveal that activation-induced shedding of
      CD16 leads to more motile behavior, allowing more targets to be engaged and
      killed in a given time.

PMID- 30108126
TI  - Dan Davis: Up close and personal with immune cells.
AB  - Davis uses microscopy and imaging approaches to study immune cell interactions.

PMID- 30108128
TI  - Aerodynamic characteristics along the wing span of a dragonfly Pantala
      flavescens.
AB  - We investigated the characteristics of interwing aerodynamic interactions across
      the span of the high aspect ratio, flexible wings of dragonflies under tethered
      and free-flying conditions. This revealed that the effects of the interactions on
      the hindwings vary across four spanwise regions. (i) Close to the wing root, a
      trailing-edge vortex (TEV) is formed by each stroke, while the formation of a
      leading-edge vortex (LEV) is limited by the short translational distance of the
      hindwing and suppressed by the forewing-induced flow. (ii) In the region away
      from the wing root but not quite up to midspan, the formation of the hindwing LEV
      is influenced by that of the forewing LEV. This vortex synergy can increase the
      circulation of the hindwing LEV in the corresponding cross-section by 22% versus
      that of the hindwing in isolation. (iii) In the region about half-way between the
      wing root and wing tip there is a transition dominated by downwash from the
      forewing resulting in flow attached to the hindwing. (iv) A LEV is developed in
      the remaining, outer region of the wing at the end of a stroke when the hindwing
      captures the vortex shed by the forewing. The interaction effects depend not only
      on the wing phasing but also on the flapping offset and flight direction. The
      aerodynamics of the hindwings vary substantially from the wing root to the wing
      tip. For a given phasing, this spanwise variation in the aerodynamics can be
      exploited in the design of artificial wings to achieve greater agility and higher
      efficiency.

PMID- 30108127
TI  - A Large Multiethnic Genome-Wide Association Study of Adult Body Mass Index
      Identifies Novel Loci.
AB  - Body mass index (BMI), a proxy measure for obesity, is determined by both
      environmental (including ethnicity, age, and sex) and genetic factors, with > 400
      BMI-associated loci identified to date. However, the impact, interplay, and
      underlying biological mechanisms among BMI, environment, genetics, and ancestry
      are not completely understood. To further examine these relationships, we
      utilized 427,509 calendar year-averaged BMI measurements from 100,418 adults from
      the single large multiethnic Genetic Epidemiology Research on Adult Health and
      Aging (GERA) cohort. We observed substantial independent ancestry and nationality
      differences, including ancestry principal component interactions and nonlinear
      effects. To increase the list of BMI-associated variants before assessing other
      differences, we conducted a genome-wide association study (GWAS) in GERA, with
      replication in the Genetic Investigation of Anthropomorphic Traits (GIANT)
      consortium combined with the UK Biobank (UKB), followed by GWAS in GERA combined
      with GIANT, with replication in the UKB. We discovered 30 novel independent BMI
      loci (P < 5.0 * 10-8) that replicated. We then assessed the proportion of BMI
      variance explained by sex in the UKB using previously identified loci compared to
      previously and newly identified loci and found slight increases: from 3.0 to 3.3%
      for males and from 2.7 to 3.0% for females. Further, the variance explained by
      previously and newly identified variants decreased with increasing age in the
      GERA and UKB cohorts, echoed in the variance explained by the entire genome,
      which also showed gene-age interaction effects. Finally, we conducted a tissue
      expression QTL enrichment analysis, which revealed that GWAS BMI-associated
      variants were enriched in the cerebellum, consistent with prior work in humans
      and mice.

PMID- 30108130
TI  - Cholecystokinin Switches the Plasticity of GABA Synapses in the Dorsomedial
      Hypothalamus via Astrocytic ATP Release.
AB  - Whether synapses in appetite-regulatory brain regions undergo long-term changes
      in strength in response to satiety peptides is poorly understood. Here we show
      that following bursts of afferent activity, the neuromodulator and satiety
      peptide cholecystokinin (CCK) shifts the plasticity of GABA synapses in the
      dorsomedial nucleus of the hypothalamus of male Sprague Dawley rats from long
      term depression to long-term potentiation (LTP). This LTP requires the activation
      of both type 2 CCK receptors and group 5 metabotropic glutamate receptors,
      resulting in a rise in astrocytic intracellular calcium and subsequent ATP
      release. ATP then acts on presynaptic P2X receptors to trigger a prolonged
      increase in GABA release. Our observations demonstrate a novel form of CCK
      mediated plasticity that requires astrocytic ATP release, and could serve as a
      mechanism for appetite regulation.SIGNIFICANCE STATEMENT Satiety peptides, like
      cholecystokinin, play an important role in the central regulation of appetite,
      but their effect on synaptic plasticity is not well understood. The current data
      provide novel evidence that cholecystokinin shifts the plasticity from long-term
      depression to long-term potentiation at GABA synapses in the rat dorsomedial
      nucleus of the hypothalamus. We also demonstrate that this plasticity requires
      the concerted action of cholecystokinin and glutamate on astrocytes, triggering
      the release of the gliotransmitter ATP, which subsequently increases GABA release
      from neighboring inhibitory terminals. This research reveals a novel neuropeptide
      induced switch in the direction of synaptic plasticity that requires astrocytes,
      and could represent a new mechanism by which cholecystokinin regulates appetite.

PMID- 30108129
TI  - Interneuron Simplification and Loss of Structural Plasticity As Markers of Aging
      Related Functional Decline.
AB  - Changes in excitatory neuron and synapse structure have been recognized as a
      potential physical source of age-related cognitive decline. Despite the
      importance of inhibition to brain plasticity, little is known regarding aging
      associated changes to inhibitory neurons. Here we test for age-related cellular
      and circuit changes to inhibitory neurons of mouse visual cortex. We find no
      substantial difference in inhibitory neuron number, inhibitory neuronal subtypes,
      or synapse numbers within the cerebral cortex of aged mice compared with younger
      adults. However, when comparing cortical interneuron morphological parameters, we
      find differences in complexity, suggesting that arbors are simplified in aged
      mice. In vivo two-photon microscopy has previously shown that in contrast to
      pyramidal neurons, inhibitory interneurons retain a capacity for dendritic
      remodeling in the adult. We find that this capacity diminishes with age and is
      accompanied by a shift in dynamics from balanced branch additions and retractions
      to progressive prevalence of retractions, culminating in a dendritic arbor that
      is both simpler and more stable. Recording of visually evoked potentials shows
      that aging-related interneuron dendritic arbor simplification and reduced
      dynamics go hand in hand with loss of induced stimulus-selective response
      potentiation (SRP), a paradigm for adult visual cortical plasticity. Chronic
      treatment with the antidepressant fluoxetine reversed deficits in interneuron
      structural dynamics and restored SRP in aged animals. Our results support a
      structural basis for age-related impairments in sensory perception, and suggest
      that declines in inhibitory neuron structural plasticity during aging contribute
      to reduced functional plasticity.SIGNIFICANCE STATEMENT Structural alterations in
      neuronal morphology and synaptic connections have been proposed as a potential
      physical basis for age-related decline in cognitive function. Little is known
      regarding aging-associated changes to inhibitory neurons, despite the importance
      of inhibitory circuitry to adult cortical plasticity and the reorganization of
      cortical maps. Here we show that brain aging goes hand in hand with progressive
      structural simplification and reduced plasticity of inhibitory neurons, and a
      parallel decline in sensory map plasticity. Fluoxetine treatment can attenuate
      the concurrent age-related declines in interneuron structural and functional
      plasticity, suggesting it could provide an important therapeutic approach for
      mitigating sensory and cognitive deficits associated with aging.

PMID- 30108131
TI  - Functions of unconventional mammalian translational GTPases GTPBP1 and GTPBP2.
AB  - GTP-binding protein 1 (GTPBP1) and GTPBP2 comprise a divergent group of
      translational GTPases with obscure functions, which are most closely related to
      eEF1A, eRF3, and Hbs1. Although recent reports implicated GTPBPs in mRNA
      surveillance and ribosome-associated quality control, how they perform these
      functions remains unknown. Here, we demonstrate that GTPBP1 possesses eEF1A-like
      elongation activity, delivering cognate aminoacyl-transfer RNA (aa-tRNA) to the
      ribosomal A site in a GTP-dependent manner. It also stimulates exosomal
      degradation of mRNAs in elongation complexes. The kinetics of GTPBP1-mediated
      elongation argues against its functioning in elongation per se but supports
      involvement in mRNA surveillance. Thus, GTP hydrolysis by GTPBP1 is not followed
      by rapid peptide bond formation, suggesting that after hydrolysis, GTPBP1 retains
      aa-tRNA, delaying its accommodation in the A site. In physiological settings,
      this would cause ribosome stalling, enabling GTPBP1 to elicit quality control
      programs; e.g., by recruiting the exosome. GTPBP1 can also deliver deacylated
      tRNA to the A site, indicating that it might function via interaction with
      deacylated tRNA, which accumulates during stresses. Although GTPBP2's binding to
      GTP was stimulated by Phe-tRNAPhe, suggesting that its function might also
      involve interaction with aa-tRNA, GTPBP2 lacked elongation activity and did not
      stimulate exosomal degradation, indicating that GTPBP1 and GTPBP2 have different
      functions.

PMID- 30108133
TI  - Enhanced Radiosensitivity in Solid Tumors using a Tumor-selective Alkyl
      Phospholipid Ether Analog.
AB  - Antitumor alkyl phospholipid (APL) analogs comprise a group of structurally
      related molecules with remarkable tumor selectivity. Some of these compounds have
      shown radiosensitizing capabilities. CLR127 is a novel, clinical-grade antitumor
      APL ether analog, a subtype of synthetic APL broadly targeting cancer cells with
      limited uptake in normal tissues. The purpose of this study was to investigate
      the effect of CLR127 to modulate radiation response across several adult and
      pediatric cancer types in vitro as well as in murine xenograft models of human
      prostate adenocarcinoma, neuroblastoma, Ewing sarcoma, and rhabdomyosarcoma. In
      vitro, CLR127 demonstrated selective uptake in cancer cells compared to normal
      cells. In cancer cells, CLR127 treatment prior to radiation significantly
      decreased clonogenic survival in vitro, and led to increased radiation-induced
      double-stranded DNA (dsDNA) breakage compared with radiation alone, which was not
      observed in normal controls. In animal models, CLR127 effectively increased the
      antitumor response to fractionated radiotherapy and led to delayed tumor regrowth
      at potentially clinically achievable doses. In conclusion, our study highlights
      the ability of CLR127 to increase radiation response in several cancer types.
      Given almost universal uptake of CLR127 in malignant cells, future research
      should test whether the observed effects can be extended to other tumor types.
      Our data provide a strong rationale for clinical testing of CLR127 as a tumor
      targeted radiosensitizing agent. Mol Cancer Ther; 17(11); 2320-8. (c)2018 AACR.

PMID- 30108134
TI  - Identification of an oncogenic network with prognostic and therapeutic value in
      prostate cancer.
AB  - Identifying critical pathways governing disease progression is essential for
      accurate prognosis and effective therapy. We developed a broadly applicable and
      novel systems-level gene discovery strategy. This approach focused on
      constitutively active androgen receptor (AR) splice variant-driven pathways as
      representative of an intractable mechanism of prostate cancer (PC) therapeutic
      resistance. We performed a meta-analysis of human prostate samples using weighted
      gene co-expression network analysis combined with experimental AR variant
      transcriptome analyses. An AR variant-driven gene module that is upregulated
      during human PC progression was identified. We filtered this module by
      identifying genes that functionally interacted with AR variants using a high
      throughput synthetic genetic array screen in Schizosaccharomyces pombe This
      strategy identified seven AR variant-regulated genes that also enhance AR
      activity and drive cancer progression. Expression of the seven genes predicted
      poor disease-free survival in large independent PC patient cohorts. Pharmacologic
      inhibition of interacting members of the gene set potently and synergistically
      decreased PC cell proliferation. This unbiased and novel gene discovery strategy
      identified a clinically relevant, oncogenic, interacting gene hub with strong
      prognostic and therapeutic potential in PC.

PMID- 30108135
TI  - Effects of Fill Volume and Humidification on Aerosol Delivery During Single-Limb
      Noninvasive Ventilation.
AB  - BACKGROUND: The aim of this work was to determine the effect of fill volume and
      humidification change on aerosol delivery during single-limb noninvasive
      ventilation (NIV). METHODS: Four groups were recruited, each consisting of 12
      subjects (6 females) with COPD receiving NIV. Groups 1 and 3 received inhaled
      salbutamol with a vibrating mesh nebulizer, and Groups 2 and 4 received inhaled
      salbutamol with a jet nebulizer. The in vivo study was carried out on days 1 and
      3. In groups 1 and 2, 2 fill-volumes were delivered to each subject; 1 mL 5,000
      MUg/mL salbutamol respirable solution used as it is or diluted to a total of 2 mL
      using normal saline. In groups 3 and 4, 1 mL 5,000 MUg/mL salbutamol respirable
      solution diluted to 2 mL total volume using normal saline was delivered to each
      subject with and without humidification. Unchanged salbutamol in urine at 30 min
      (USAL0.5) and in pooled urine at 24 h (USAL24) was determined. On day 2, the ex
      vivo study was carried out on subjects using the same experimental setting with a
      filter placed proximal to their face mask for collection of total inhaled dose of
      salbutamol (aerosol emitted). RESULTS: The vibrating mesh nebulizer delivered
      higher USAL0.5, USAL24, and aerosol emitted compared to the jet nebulizer at all
      fill volumes and humidification conditions (P < .001). Increasing fill volume
      from 1 mL to 2 mL resulted in a significant increase in USAL0.5, USAL24, and
      aerosol emitted from the jet nebulizer (P < .05) with an insignificant effect on
      the vibrating mesh nebulizer. A 2-mL fill volume with the jet nebulizer delivered
      USAL24 and aerosol emitted comparable to those of 1 mL with the vibrating mesh
      nebulizer with significantly longer nebulization times (P < .001). Humidification
      had an insignificant effect on aerosol delivery. CONCLUSIONS: Increasing the fill
      volume of a jet nebulizer is essential to increase the amount of inhaled
      medication reaching a subject. In contrast, there is no need to increase fill
      volumes when using a vibrating mesh nebulizer. There is no need to switch off the
      humidifier while delivering aerosol through a single-limb NIV circuit.

PMID- 30108132
TI  - Distinct patterns of histone acetyltransferase and Mediator deployment at yeast
      protein-coding genes.
AB  - The transcriptional coactivators Mediator and two histone acetyltransferase (HAT)
      complexes, NuA4 and SAGA, play global roles in transcriptional activation. Here
      we explore the relative contributions of these factors to RNA polymerase II
      association at specific genes and gene classes by rapid nuclear depletion of key
      complex subunits. We show that the NuA4 HAT Esa1 differentially affects certain
      groups of genes, whereas the SAGA HAT Gcn5 has a weaker but more uniform effect.
      Relative dependence on Esa1 and Tra1, a shared component of NuA4 and SAGA,
      distinguishes two large groups of coregulated growth-promoting genes. In
      contrast, we show that the activity of Mediator is particularly important at a
      separate, small set of highly transcribed TATA-box-containing genes. Our analysis
      indicates that at least three distinct combinations of coactivator deployment are
      used to generate moderate or high transcription levels and suggests that each may
      be associated with distinct forms of regulation.

PMID- 30108136
TI  - Improving Influenza Testing and Treatment in Hospitalized Children.
AB  - OBJECTIVES: National guidelines recommend influenza testing for children
      hospitalized with influenza-like illness (ILI) during influenza season and
      treatment of those with confirmed influenza. Using quality improvement methods,
      we sought to increase influenza testing and treatment of children admitted to our
      hospital medicine service with ILI from 65% to 90% during the 2014-2015 influenza
      season. METHODS: We targeted several key drivers using multiple plan-do-study-act
      cycles. Interventions included awareness modules, biweekly flyers, and failure
      tracking. ILI admissions (fever plus respiratory symptoms) were reviewed weekly
      once surveillance data revealed elevated influenza activity. Appropriate testing
      and treatment of ILI was defined as influenza testing and/or treatment within 24
      hours of admission unless a known cause other than influenza was present. We used
      statistical process control charts to track progress using established quality
      improvement methods. Appropriate testing and treatment was also assessed in the
      2016-2017 influenza season by using similar methods, although no new
      interventions were introduced. RESULTS: For the 2014-2015 season, appropriate
      testing and treatment increased from a baseline mean of 65% to 91% within 3
      months. For the 2016-2017 season, appropriate testing and treatment remained at a
      mean of 80% throughout the influenza season. CONCLUSIONS: Appropriate influenza
      testing and treatment increased to 90% in children with ILI during the 2014-2015
      season. Improvements were sustained in a subsequent influenza season. Our
      initiative improved recognition of influenza and likely increased treatment
      opportunities. Future work should be focused on wider implementation and further
      reducing variation.

PMID- 30108138
TI  - Antipruritic Effect of Natural Coumarin Osthole through Selective Inhibition of
      Thermosensitive TRPV3 Channel in the Skin.
AB  - Coumarin osthole is a dominant bioactive ingredient of the natural Cnidium
      monnieri plant commonly used for traditional Chinese herbal medicines for
      therapies and treatments including antipruritus and antidermatitis. However, the
      molecular mechanism underlying the action of osthole remains unclear. In this
      study, we report that osthole exerts an antipruritic effect through selective
      inhibition of Ca2+-permeable and thermosensitive transient receptor potential
      vanilloid 3 (TRPV3) cation channels that are primarily expressed in the
      keratinocytes of the skin. Coumarin osthole was identified as an inhibitor of
      TRPV3 channels transiently expressed in HEK293 cells in a calcium fluorescent
      assay. Inhibition of the TRPV3 current by osthole and its selectivity were
      further confirmed by whole-cell patch clamp recordings of TRPV3-expressing HEK293
      cells and mouse primary cultured keratinocytes. Behavioral evaluation
      demonstrated that inhibition of TRPV3 by osthole or silencing by knockout of the
      TRPV3 gene significantly reduced the scratching induced by either acetone-ether
      water or histamine in localized rostral neck skin in mice. Taken together, our
      findings provide a molecular basis for use of natural coumarin osthole from the
      C. monnieri plant in antipruritic or skin care therapy, thus establishing a
      significant role of the TRPV3 channel in chronic itch signaling or acute
      histamine-dependent itch sensation.

PMID- 30108137
TI  - TFEB enhances astroglial uptake of extracellular tau species and reduces tau
      spreading.
AB  - The progression of tau pathology in Alzheimer's disease follows a stereotyped
      pattern, and recent evidence suggests a role of synaptic connections in this
      process. Astrocytes are well positioned at the neuronal synapse to capture and
      degrade extracellular tau as it transits the synapse and hence could potentially
      have the ability to inhibit tau spreading and delay disease progression. Our
      study shows increased expression and activity of Transcription Factor EB (TFEB),
      a master regulator of lysosomal biogenesis, in response to tau pathology in both
      human brains with dementia and transgenic mouse models. Exogenous TFEB expression
      in primary astrocytes enhances tau fibril uptake and lysosomal activity, while
      TFEB knockout has the reverse effect. In vivo, induced TFEB expression in
      astrocytes reduces pathology in the hippocampus of PS19 tauopathy mice, as well
      as prominently attenuates tau spreading from the ipsilateral to the contralateral
      hippocampus in a mouse model of tau spreading. Our study suggests that astrocytic
      TFEB plays a functional role in modulating extracellular tau and the propagation
      of neuronal tau pathology in tauopathies such as Alzheimer's disease.

PMID- 30108139
TI  - Prostaglandin F2alpha promotes embryo implantation and development in the pig.
AB  - Successful establishment and development of pregnancy requires proper
      communication between developing conceptuses and the maternal reproductive tract.
      Prostaglandins are key players involved in the regulation of reproductive
      processes in mammals including pigs. Due to its luteolytic action, prostaglandin
      F2-alpha (PGF2alpha) is mainly considered as an undesirable factor during early
      pregnancy. However, its content in the uterine lumen is elevated in pigs and
      other mammals. Recently, we reported an important role of PGF2alpha in the
      endometrium during early pregnancy in the pig. Thus, the aim of the present study
      was to determine whether PGF2alpha can act on porcine trophoblast and if so, to
      elucidate what effect it could exert. We detected increased expression of
      PGF2alpha receptor during the implantation period (from day 14 until day 19 of
      pregnancy). Global gene expression profiling using microarrays and quantitative
      PCR studies revealed that PGF2alpha acting on porcine trophoblast cells in vitro
      alters expression of genes potentially involved in processes related to
      implantation, such as: cell proliferation, focal adhesion, extracellular matrix
      binding, cell migration, cytoskeleton organization, immune interactions, ion
      homeostasis, and lipid metabolism. Using primary porcine trophoblast cells, we
      demonstrated that PGF2alpha stimulated trophoblast cell proliferation and
      adhesion to extracellular matrix protein. This was likely mediated by mitogen
      activated protein kinases (MAPK1/3) and focal adhesion kinase (FAK) since we
      observed increased phosphorylation of MAPK1/3 and FAK in trophoblast cells
      treated with PGF2alpha. To conclude, the present report indicates a novel role
      for PGF2alpha in the porcine conceptus as a para- and autocrine factor supporting
      pregnancy establishment.

PMID- 30108141
TI  - Family-Driven Goals to Improve Care for Children With Autism Spectrum Disorder.
AB  - OBJECTIVES: Constipation and insomnia are not consistently identified and treated
      in children with autism spectrum disorder (ASD) despite their high prevalence and
      deleterious impact in this population. To standardize care, a constipation
      practice pathway and an insomnia practice pathway were previously developed by
      Autism Treatment Network clinicians. Our objective was to implement and refine
      these practice pathways in clinical settings. METHODS: Eleven Autism Treatment
      Network sites participated in a Learning Collaborative (ie, multidisciplinary
      quality improvement team) and chose to implement either the constipation or
      insomnia practice pathway in the clinical setting. Families set intervention
      goals (eg, increase stool frequency, decrease nighttime awakenings) before
      treatment. Each site began implementation with 1 patient and then increased
      implementation by factors of 5. Before each increase, the Learning Collaborative
      evaluated progress and refined the practice pathways. Process improvement was
      measured primarily by duration until goal attainment and by percentage of
      families who meet their goals. RESULTS: Across sites, 82 children with ASD and
      constipation and 101 children with ASD and insomnia were managed. Difficulties
      with intervention adherence and communication between providers and families were
      reported and were subsequently improved with parallel refinements to both
      practice pathways. The most notable modification was incorporating a goal-setting
      session in which families generated their own intervention goals (ie, family
      driven goals). In this quality improvement initiative, 75% of families met at
      least 1 constipation or insomnia goal, with the median time to improvement being
      6 weeks. CONCLUSIONS: By integrating a family-centered approach into the
      standardization of care, constipation and insomnia practice pathways may improve
      engagement, adherence, and management of medical conditions in children with ASD.

PMID- 30108142
TI  - Lung Ultrasound Score Predicts Surfactant Need in Extremely Preterm Neonates.
AB  - BACKGROUND AND OBJECTIVES: There are several lung ultrasound scores (LUS) for
      evaluating lung aeration in critically ill adults with restrictive lung
      disorders. A modified LUS adapted for neonates correlates well with oxygenation
      and is able to be used to predict the need for surfactant in preterm neonates
      with respiratory distress syndrome (RDS). However, no data are available for
      extremely preterm neonates for whom timely surfactant administration is
      especially important. We hypothesized that LUS might be reliable in extremely
      preterm neonates with RDS who are treated with continuous positive airway
      pressure. We aimed to determine the diagnostic accuracy of LUS in predicting the
      need for surfactant treatment and re-treatment in this population. METHODS: We
      performed a prospective cohort diagnostic accuracy study between 2015 and 2016 in
      a tertiary-care academic center. Inborn neonates at <=30 weeks' gestation with
      RDS treated with continuous positive airway pressure were eligible. Surfactant
      was given on the basis of oxygen requirement thresholds derived from European
      guidelines, and a LUS was not used to guide surfactant treatment. We calculated
      the LUS after admission and analyzed its diagnostic accuracy to predict
      surfactant treatment and re-treatment. RESULTS: We enrolled 133 infants; 68 (51%)
      received 1 dose of surfactant and 19 (14%) received 2 surfactant doses. A LUS is
      significantly correlated with oxygenation index (rho = 0.6; P < .0001) even after
      adjustment for gestational age (P < .0001). A LUS can be used to accurately
      predict the need for the first surfactant dose (area under the curve = 0.94; 95%
      confidence interval: 0.90-0.98; P < .0001) and also the need for surfactant
      redosing (area under the curve = 0.803; 95% confidence interval: 0.72-0.89; P <
      .0001). The global accuracy for the prediction of surfactant treatment and re
      treatment is 89% and 72%, respectively. CONCLUSIONS: LUS may be used to predict
      the need for surfactant replacement in extremely preterm neonates with RDS.

PMID- 30108140
TI  - Synchrotron-Based X-Ray Fluorescence Microscopy as a Technique for Imaging of
      Elements in Plants.
AB  - Understanding the distribution of elements within plant tissues is important
      across a range of fields in plant science. In this review, we examine synchrotron
      based x-ray fluorescence microscopy (XFM) as an elemental imaging technique in
      plant sciences, considering both its historical and current uses as well as
      discussing emerging approaches. XFM offers several unique capabilities of
      interest to plant scientists, including in vivo analyses at room temperature and
      pressure, good detection limits (approximately 1-100 mg kg-1), and excellent
      resolution (down to 50 nm). This has permitted its use in a range of studies,
      including for functional characterization in molecular biology, examining the
      distribution of nutrients in food products, understanding the movement of foliar
      fertilizers, investigating the behavior of engineered nanoparticles, elucidating
      the toxic effects of metal(loid)s in agronomic plant species, and studying the
      unique properties of hyperaccumulating plants. We anticipate that continuing
      technological advances at XFM beamlines also will provide new opportunities
      moving into the future, such as for high-throughput screening in molecular
      biology, the use of exotic metal tags for protein localization, and enabling time
      resolved, in vivo analyses of living plants. By examining current and potential
      future applications, we hope to encourage further XFM studies in plant sciences
      by highlighting the versatility of this approach.

PMID- 30108143
TI  - Novel Technologies for Neonatal Care: The Case of Point-of-Care Lung
      Ultrasonography.

PMID- 30108144
TI  - Oligodendrocyte precursor survival and differentiation requires chromatin
      remodeling by Chd7 and Chd8.
AB  - Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in
      the adult brain, and deregulation of OPC proliferation-differentiation balance
      results in either glioma formation or defective adaptive (re)myelination. OPC
      differentiation requires significant genetic reprogramming, implicating chromatin
      remodeling. Mounting evidence indicates that chromatin remodelers play important
      roles during normal development and their mutations are associated with
      neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE
      syndrome and CHD8 being one of the strongest autism spectrum disorder (ASD) high
      risk-associated genes. Herein, we report on uncharacterized functions of the
      chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin binding profile,
      combined with transcriptome and chromatin accessibility analyses of Chd7-deleted
      OPCs, demonstrates that Chd7 protects nonproliferative OPCs from apoptosis by
      chromatin closing and transcriptional repression of p53 Furthermore, Chd7
      controls OPC differentiation through chromatin opening and transcriptional
      activation of key regulators, including Sox10, Nkx2.2, and Gpr17 However, Chd7 is
      dispensable for oligodendrocyte stage progression, consistent with Chd8
      compensatory function, as suggested by their common chromatin-binding profiles
      and genetic interaction. Finally, CHD7 and CHD8 bind in OPCs to a majority of ASD
      risk-associated genes, suggesting an implication of oligodendrocyte lineage cells
      in ASD neurological defects. Our results thus offer new avenues to understand and
      modulate the CHD7 and CHD8 functions in normal development and disease.

PMID- 30108145
TI  - Crystal Structure of a ligand-bound LacY-Nanobody Complex.
AB  - The lactose permease of Escherichia coli (LacY), a dynamic polytopic membrane
      transport protein, catalyzes galactoside/H+ symport and operates by an
      alternating access mechanism that exhibits multiple conformations, the
      distribution of which is altered by sugar-binding. Camelid nanobodies were made
      against a double-mutant Gly46 -> Trp/Gly262 -> Trp (LacYWW) that produces an
      outward-open conformation, as opposed to the cytoplasmic open-state crystal
      structure of WT LacY. Nanobody 9047 (Nb9047) stabilizes WT LacY in a periplasmic
      open conformation. Here, we describe the X-ray crystal structure of a complex
      between LacYWW, the high-affinity substrate analog 4-nitrophenyl-alpha-d
      galactoside (NPG), and Nb9047 at 3-A resolution. The present crystal structure
      demonstrates that Nb9047 binds to the periplasmic face of LacY, primarily to the
      C-terminal six-helical bundle, while a flexible loop of the Nb forms a bridge
      between the N- and C-terminal halves of LacY across the periplasmic vestibule.
      The bound Nb partially covers the vestibule, yet does not affect the on-rates or
      off-rates for the substrate binding to LacYWW, which implicates dynamic
      flexibility of the Nb-LacYWW complex. Nb9047-binding neither changes the overall
      structure of LacYWW with bound NPG, nor the positions of side chains comprising
      the galactoside-binding site. The current NPG-bound structure exhibits a more
      occluded periplasmic vestibule than seen in a previous structure of a (different
      Nb) apo-LacYWW/Nb9039 complex that we argue is caused by sugar-binding, with
      major differences located at the periplasmic ends of transmembrane helices in the
      N-terminal half of LacY.

PMID- 30108146
TI  - Generating carbon schwarzites via zeolite-templating.
AB  - Zeolite-templated carbons (ZTCs) comprise a relatively recent material class
      synthesized via the chemical vapor deposition of a carbon-containing precursor on
      a zeolite template, followed by the removal of the template. We have developed a
      theoretical framework to generate a ZTC model from any given zeolite structure,
      which we show can successfully predict the structure of known ZTCs. We use our
      method to generate a library of ZTCs from all known zeolites, to establish
      criteria for which zeolites can produce experimentally accessible ZTCs, and to
      identify over 10 ZTCs that have never before been synthesized. We show that ZTCs
      partition space into two disjoint labyrinths that can be described by a pair of
      interpenetrating nets. Since such a pair of nets also describes a triply periodic
      minimal surface (TPMS), our results establish the relationship between ZTCs and
      schwarzites-carbon materials with negative Gaussian curvature that resemble TPMSs
      linking the research topics and demonstrating that schwarzites should no longer
      be thought of as purely hypothetical materials.

PMID- 30108147
TI  - Oceanographic boundaries constrain microbial diversity gradients in the South
      Pacific Ocean.
AB  - Marine microbes along with microeukaryotes are key regulators of oceanic
      biogeochemical pathways. Here we present a high-resolution (every 0.5 degrees  of
      latitude) dataset describing microbial pro- and eukaryotic richness in the
      surface and just below the thermocline along a 7,000-km transect from 66 degrees
      S at the Antarctic ice edge to the equator in the South Pacific Ocean. The
      transect, conducted in austral winter, covered key oceanographic features
      including crossing of the polar front (PF), the subtropical front (STF), and the
      equatorial upwelling region. Our data indicate that temperature does not
      determine patterns of marine microbial richness, complementing the global model
      data from Ladau et al. [Ladau J, et al. (2013) ISME J 7:1669-1677]. Rather, NH4+,
      nanophytoplankton, and primary productivity were the main drivers for archaeal
      and bacterial richness. Eukaryote richness was highest in the least-productive
      ocean region, the tropical oligotrophic province. We also observed a unique
      diversity pattern in the South Pacific Ocean: a regional increase in archaeal and
      bacterial diversity between 10 degrees S and the equator. Rapoport's rule
      describes the tendency for the latitudinal ranges of species to increase with
      latitude. Our data showed that the mean latitudinal ranges of archaea and
      bacteria decreased with latitude. We show that permanent oceanographic features,
      such as the STF and the equatorial upwelling, can have a significant influence on
      both alpha-diversity and beta-diversity of pro- and eukaryotes.

PMID- 30108149
TI  - Reply to Jung et al.: Default neglect persists over time and across contexts.

PMID- 30108148
TI  - Structure of the mammalian TRPM7, a magnesium channel required during embryonic
      development.
AB  - The transient receptor potential ion channel subfamily M, member 7 (TRPM7), is a
      ubiquitously expressed protein that is required for mouse embryonic development.
      TRPM7 contains both an ion channel and an alpha-kinase. The channel domain
      comprises a nonselective cation channel with notable permeability to Mg2+ and
      Zn2+ Here, we report the closed state structures of the mouse TRPM7 channel
      domain in three different ionic conditions to overall resolutions of 3.3, 3.7,
      and 4.1 A. The structures reveal key residues for an ion binding site in the
      selectivity filter, with proposed partially hydrated Mg2+ ions occupying the
      center of the conduction pore. In high [Mg2+], a prominent external disulfide
      bond is found in the pore helix, which is essential for ion channel function. Our
      results provide a structural framework for understanding the TRPM1/3/6/7
      subfamily and extend the knowledge base upon which to study the diversity and
      evolution of TRP channels.

PMID- 30108150
TI  - People can recognize, learn, and apply default effects in social influence.

PMID- 30108152
TI  - The potential of human induced pluripotent stem cells for modelling diabetic
      wound healing in vitro.
AB  - Impaired wound healing and ulceration caused by diabetes mellitus, is a
      significant healthcare burden, markedly impairs quality of life for patients, and
      is the major cause of amputation worldwide. Current experimental approaches used
      to investigate the complex wound healing process often involve cultures of
      fibroblasts and/or keratinocytes in vitro, which can be limited in terms of
      complexity and capacity, or utilisation of rodent models in which the mechanisms
      of wound repair differ substantively from that in humans. However, advances in
      tissue engineering, and the discovery of strategies to reprogramme adult somatic
      cells to pluripotency, has led to the possibility of developing models of human
      skin on a large scale. Generation of induced pluripotent stem cells (iPSCs) from
      tissues donated by diabetic patients allows the (epi)genetic background of this
      disease to be studied, and the ability to differentiate iPSCs to multiple cell
      types found within skin may facilitate the development of more complex skin
      models; these advances offer key opportunities for improving modelling of wound
      healing in diabetes, and the development of effective therapeutics for treatment
      of chronic wounds.

PMID- 30108153
TI  - Angiotensin II induces cholesterol accumulation and impairs insulin secretion by
      regulating ABCA1 in beta cells.
AB  - In pancreatic beta cells, ABCA1, a 254 kDa membrane protein, affects cholesterol
      homeostasis and insulin secretion. Angiotensin II, as the main effector of the
      renin-angiotensin system, decreases glucose-stimulated insulin secretion (GSIS).
      We examined the effect of angiotensin II on ABCA1 expression in primary
      pancreatic islets and INS-1 cells. Angiotensin II decreased ABCA1 protein and
      mRNA; angiotensin II type 1 receptor (AT1R) blockade rescued this ABCA1
      repression. In parallel, angiotensin II suppressed the promoter activity of
      ABCA1, an effect that was abrogated by PD98095, a specific inhibitor of MAPK
      kinase (MEK). LXR enhanced ABCA1 promoter activity, and angiotensin II decreased
      the nuclear abundance of LXR protein. On a chromatin immunoprecipitation assay,
      LXR mediated the transcription of ABCA1 by directly binding to its promoter.
      Mutation of the LXR binding site on the ABCA1 promoter cancelled the effect of
      angiotensin II. Furthermore, angiotensin II induced cholesterol accumulation and
      impaired GSIS; inhibition of AT1R or MEK pathway reversed these effects. In
      summary, our study showed that angiotensin II suppressed ABCA1 expression in
      pancreatic islets and INS-1 cells, indicating that angiotensin II may influence
      GSIS by regulating ABCA1 expression. Additional research may address therapeutic
      needs in diseases such as diabetes mellitus.

PMID- 30108154
TI  - Metabolism of a synthetic compared with a natural therapeutic pulmonary
      surfactant in adult mice.
AB  - Secreted pulmonary surfactant phosphatidylcholine (PC) has a complex intra
      alveolar metabolism that involves uptake and recycling by alveolar type II
      epithelial cells, catabolism by alveolar macrophages, and loss up the bronchial
      tree. We compared the in vivo metabolism of animal-derived poractant alfa
      (Curosurf) and a synthetic surfactant (CHF5633) in adult male C57BL/6 mice. The
      mice were dosed intranasally with either surfactant (80 mg/kg body weight)
      containing universally 13C-labeled dipalmitoyl PC (DPPC) as a tracer. The loss of
      [U13C]DPPC from bronchoalveolar lavage and lung parenchyma, together with the
      incorporation of 13C-hydrolysis fragments into new PC molecular species, was
      monitored by electrospray ionization tandem mass spectrometry. The catabolism of
      CHF5633 was considerably delayed compared with poractant alfa, the hydrolysis
      products of which were cleared more rapidly. There was no selective resynthesis
      of DPPC and, strikingly, acyl remodeling resulted in preferential synthesis of
      polyunsaturated PC species. In conclusion, both surfactants were metabolized by
      similar pathways, but the slower catabolism of CHF5633 resulted in longer
      residence time in the airways and enhanced recycling of its hydrolysis products
      into new PC species.

PMID- 30108155
TI  - Genome-wide association study identifies novel recessive genetic variants for
      high TGs in an Arab population.
AB  - Abnormal blood lipid levels are influenced by genetic and lifestyle/dietary
      factors. Although many genetic variants associated with blood lipid traits have
      been identified in Europeans, similar data in Middle Eastern populations are
      limited. We performed a genome-wide association study with Arab individuals
      (discovery cohort: 1,353; replication cohort: 1,176) from Kuwait to identify
      possible associations of genetic variants with high lipid levels. We used
      Illumina HumanOmniExpress BeadChip and candidate SNP genotyping in the discovery
      and replication phases, respectively. For association tests, we used genetic
      models that were based on additive and recessive modes of inheritance. High
      triglycerides (TGs) were recessively associated with six risk variants
      (rs1002487/RPS6KA1, rs11805972/LAD1) rs7761746/Or5v1, rs39745/CTTNBP2-LSM8,
      rs2934952/PGAP3, and rs9626773/RP11-191L9.4-CERK) at genome-wide significance (P
      ? 6.12E-09), and another six variants (rs10873925/ST6GALNAC5, rs4663379/SPP2
      ARL4C, rs10033119/NPY1R, rs17709449/LINC00911-FLRT2, rs11654954/CDK12-NEUROD2,
      and rs9972882/STARD3) were associated at borderline significance (P ? 5.0E-08).
      High TG was also additively associated with rs11654954. All of the 12 identified
      markers are novel and are harbored in runs of homozygosity. Literature evidence
      supports the involvement of these gene loci in lipid-related processes. This
      study in an Arab population augments international efforts to identify genetic
      regulation of lipid traits.

PMID- 30108157
TI  - Amyloid Precursor Protein Is Associated with Aggressive Behavior in Nonluminal
      Breast Cancers.
AB  - BACKGROUND: beta-amyloid precursor protein (APP), a potential target for
      Alzheimer's disease treatment, has recently been shown to take part in
      carcinogenesis. Increased APP promotes migration, survival, and proliferation in
      breast cancer cell lines. We examined the clinical value of APP in breast
      cancers. A comprehensive examination of clinicopathological features related to
      APP expression in a large cohort of breast cancers and the corresponding
      metastatic lymph nodes was performed. APP expression and its prognostic impact in
      different breast cancer subtypes were examined. RESULTS: APP was highly expressed
      in nonluminal breast cancers and correlated with features associated with
      nonluminal breast cancers (including higher grade, the presence of necrosis, and
      higher proliferative index, growth factor receptor, and basal marker expression).
      Multivariate Cox hazard analysis demonstrated that APP was an independent adverse
      prognostic factor of disease-free survival (DFS; hazard ratio [HR], 2.090; p =
      .013; 95% confidence interval [CI], 1.165-3.748) and breast cancer-specific
      survival (BCSS; HR, 2.631; p = .002; 95% CI, 1.408-4.915) in the nonluminal
      group. The independent prognostic impact was also seen in triple negative breast
      cancers. Interestingly, a higher expression of APP was found in nodal metastasis
      compared with primary tumor. Such APP upregulation was correlated with further
      distal metastasis and poorer outcome (DFS: log-rank, 12.848; p < .001; BCSS: log
      rank, 13.947; p < .001). CONCLUSION: Our findings provided evidence of oncogenic
      roles of APP in clinical breast cancers. Patients with positive APP expression,
      particularly those with APP upregulation in lymph node metastases, may require
      vigilant monitoring of their disease and more aggressive therapy. IMPLICATIONS
      FOR PRACTICE: beta-amyloid precursor protein (APP), a potential target for
      Alzheimer's disease, has recently been implicated in oncogenesis. Here, evidence
      of its roles in clinical breast cancers is provided. Positive APP expression was
      found to be an independent prognostic factor in nonluminal cancers, particularly
      triple negative breast cancers (TNBCs). Interestingly, a higher APP in nodal
      metastases was associated with distal metastases. TNBCs are heterogeneous and
      currently have no available target therapy. APP could have therapeutic potential
      and be used to define the more aggressive cases in TNBCs. Current prognostic
      analysis is based on primary tumor. The present data suggest that investigation
      of nodal metastases could provide additional prognostic value.

PMID- 30108156
TI  - Comprehensive Genomic Profiling of Hodgkin Lymphoma Reveals Recurrently Mutated
      Genes and Increased Mutation Burden.
AB  - BACKGROUND: The genomic landscape of Hodgkin lymphoma (HL) has been difficult to
      characterize due to the paucity of neoplastic cells and an abundant
      microenvironment. Such characterization is needed in order to improve treatment
      strategies. MATERIALS AND METHODS: We performed comprehensive genomic profiling
      (CGP) using targeted next-generation sequencing on archival formalin-fixed
      paraffin embedded tumor samples from 63 patients to analyze the landscape of HL.
      RESULTS: CGP was successful for 49/63 archival specimens (78%), and revealed
      aberrations impacting genes including B2M, TP53, and XPO1 (E571). Of the 34
      patients for whom total mutation burden (TMB; mutations/megabase [Mb]) was
      assessed, 5 (15%) had high TMB (>=20 mutations/Mb), 18 (53%) had intermediate TMB
      (6-19 mutations/Mb), and 11 (32%) had low TMB (<=5 mutations/Mb). We next tested
      13 patients' plasma cell-free DNA with droplet digital polymerase chain reaction
      for the presence of XPO1 E571 mutation, which was confirmed in the plasma of 31%
      of patients. In three patients with serially collected plasma samples, XPO1 E571K
      allelic frequency changes corresponded with changes in tumor size on conventional
      radiographic imaging. CONCLUSION: The study demonstrates that comprehensive
      genomic profiling of archival Hodgkin lymphoma tumor samples is feasible and
      leads to the identification of genes that are recurrently mutated and that
      Hodgkin lymphoma has increased mutation burden in the majority of samples
      analyzed. Furthermore, tracking of XPO1 E571 mutant allele frequency in a subset
      of patients may also represent a potential disease-monitoring strategy and
      warrants further investigation. IMPLICATIONS FOR PRACTICE: This study provides
      the first evidence that comprehensive genomic profiling can be performed to map
      the genomic landscape of Hodgkin lymphoma and that a subpopulation of patients
      has mutations in TP53, B2M, XPO1, and other genes. It was found that 15% of
      patients have high mutation burden, which, in cancers such as melanoma, may
      indicate sensitivity to immune checkpoint inhibitors, and may thus be explored
      for Hodgkin lymphoma. Lastly, this work demonstrates that changes in the mutant
      allele frequency of XPO1 in serially collected plasma cell-free DNA samples
      correspond with treatment outcomes measured with conventional radiographic
      imaging.

PMID- 30108158
TI  - Inhibition of Multidrug Resistance Proteins by MK 571 Enhances Bladder, Prostate,
      and Urethra Relaxation through cAMP or cGMP Accumulation.
AB  - The biologic effect of cAMP and cGMP is terminated by phosphodiesterases and
      multidrug resistance proteins MRP4 and MRP5, which pump cyclic nucleotides out of
      the cell. Therefore, this study aimed to characterize the role of MRP inhibitor,
      MK 571 (3-[[[3-[(1E)-2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-(dimethylamino)
      3-oxopropyl]thio]methyl]thio]propanoic acid), in the bladder, prostate, and
      urethra of male mice by means of functional assays, protein expression, and
      cyclic nucleotide quantification. The cumulative addition of MK 571 (1-30 uM)
      produced only small relaxation responses (approximately 25%) in all studied
      tissues. In the bladder, isoprenaline/fenoterol and forskolin concentration
      dependently relaxed and MK 571 (20 uM) increased the maximal response values by
      37% and 24%, respectively. When MK 571 was coincubated with fenoterol or
      forskolin, intracellular levels of cAMP and protein expression of phospho
      vasodilator-stimulated phosphoprotein (p-VASP) Ser157 were significantly greater
      compared with bladders stimulated with fenoterol or forskolin alone. In the
      prostate and urethra, sodium nitroprusside concentration-dependently relaxed and
      MK 571 (20 uM) significantly increased relaxation responses by 70% and 56%,
      respectively, accompanied by greater intracellular levels of cGMP and protein
      expression of p-VASP Ser239 in the prostate. Tadalafil and BAY 41-2272 (5
      cyclopropyl-2-[1-[(2-fluorophenyl)methyl]-1H-pyrazolo[3,4-b]pyridin-3-yl]-4
      pyrimidinamine) also relaxed the prostate and urethra, respectively, and MK 571
      markedly enhanced this response. The stable analog of cGMP (8-Br-cGMP) induced
      concentration-dependent relaxation responses in the prostate and urethra, and MK
      571 significantly increased the relaxation response. In conclusion, to our
      knowledge, this is the first study to show that efflux transporters are
      physiologically active in the bladder, prostate, and urethra to control
      intracellular levels of cAMP or cGMP.

PMID- 30108159
TI  - In Vitro Pharmacological Characterization of Buprenorphine, Samidorphan, and
      Combinations Being Developed as an Adjunctive Treatment of Major Depressive
      Disorder.
AB  - A combination of buprenorphine (BUP) and samidorphan (SAM) at a 1:1 (mg/mg) fixed
      ratio dose is being investigated as an adjunctive treatment of major depressive
      disorder (BUP/SAM, ALKS 5461). Both [3H]BUP and [3H]SAM bound to the MU-, kappa-,
      and delta-opioid receptors (MOR, KOR, and DOR, respectively) with Kd values of 3
      nM or less. [3H]BUP dissociated from the MOR more slowly than [3H]SAM did. In the
      [35S]GTPgammaS assay, BUP was a partial agonist at the MOR, KOR, and DOR. SAM was
      an antagonist at the MOR and a partial agonist at the KOR and DOR. The
      pharmacology of the combination of SAM and BUP was characterized at ratios like
      the molar ratios of both compounds at steady state in humans. In all assessments,
      SAM reduced the efficacy of BUP at the MOR without altering its potency. At the
      KOR, SAM had no significant effect on the activity of BUP. In bioluminescent
      resonance energy transfer assays, SAM, naltrexone, and naloxone were partial
      agonists when the MOR was coupled to the Galpha oB and Galpha z, and were
      antagonists when coupled to Galpha i At the KOR, SAM was a partial agonist
      activating Galpha oA and Galpha oB and a full agonist in stimulating Galpha z SAM
      inhibited BUP's recruitment of beta-arrestin to the MOR, suggesting an
      attenuation of BUP's efficacy in activating G proteins correlated with an
      inhibition of beta-arrestin recruitment. The collective data suggest that SAM
      attenuates the efficacy of BUP under all conditions tested at the MOR and DOR but
      had little effect on BUP activity at the KOR.

PMID- 30108160
TI  - Impairment of Nitric Oxide Pathway by Intravascular Hemolysis Plays a Major Role
      in Mice Esophageal Hypercontractility: Reversion by Soluble Guanylyl Cyclase
      Stimulator.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) patients display exaggerated
      intravascular hemolysis and esophageal disorders. Since excess hemoglobin in the
      plasma causes reduced nitric oxide (NO) bioavailability and oxidative stress, we
      hypothesized that esophageal contraction may be impaired by intravascular
      hemolysis. This study aimed to analyze the alterations of the esophagus
      contractile mechanisms in a murine model of exaggerated intravascular hemolysis
      induced by phenylhydrazine (PHZ). For comparative purposes, sickle cell disease
      (SCD) mice were also studied, a less severe intravascular hemolysis model.
      Esophagus rings were dissected free and placed in organ baths. Plasma hemoglobin
      was higher in PHZ compared with SCD mice, as expected. The contractile responses
      produced by carbachol (CCh), KCl, and electrical-field stimulation (EFS) were
      superior in PHZ esophagi compared with control but remained unchanged in SCD
      mice. Preincubation with the NO-independent soluble guanylate cyclase stimulator
      3-(4-amino-5-cyclopropylpyrimidin-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4
      b]pyridine (BAY 41-2272; 1 MUM) completely reversed the increased contractile
      responses to CCh, KCl, and EFS in PHZ mice, but responses remained unchanged with
      prior treatment with NO donor sodium nitroprusside (300 MUM). Protein expression
      of 3-nitrotyrosine and 4-hydroxynonenal increased in esophagi from PHZ mice,
      suggesting a state of oxidative stress. In endothelial nitric oxide synthase gene
      deficient mice, the contractile responses elicited by KCl and CCh were increased
      in the esophagus but remained unchanged with the intravascular hemolysis induced
      by PHZ. In conclusion, our results show that esophagus hypercontractile state
      occurs in association with lower NO bioavailability due to exaggerated hemolysis
      intravascular and oxidative stress. Moreover, our study supports the hypothesis
      that esophageal disorders in PNH patients are secondary to intravascular
      hemolysis affecting the NO-cGMP pathway.

PMID- 30108161
TI  - Tamoxifen Directly Interacts with the Dopamine Transporter.
AB  - The selective estrogen receptor modulator tamoxifen increases extracellular
      dopamine in vivo and acts as a neuroprotectant in models of dopamine
      neurotoxicity. We investigated the effect of tamoxifen on dopamine transporter
      (DAT)-mediated dopamine uptake, dopamine efflux, and [3H]WIN 35,428 [(-)-2-beta
      carbomethoxy-3-beta-(4-fluorophenyl)tropane] binding in rat striatal tissue.
      Tamoxifen dose-dependently blocked dopamine uptake (54% reduction at 10 MUM) and
      amphetamine-stimulated efflux (59% reduction at 10 MUM) in synaptosomes. It also
      produced a small but significant reduction in [3H]WIN 35,428 binding in striatal
      membranes, indicating a weak interaction with the substrate binding site in the
      DAT. Biotinylation and cysteine accessibility studies indicated that tamoxifen
      stabilizes the outward-facing conformation of the DAT in a cocaine-like manner
      and does not affect surface expression of the DAT. Additional studies with mutant
      DAT constructs D476A and I159A suggested a direct interaction between tamoxifen
      and a secondary substrate binding site of the transporter. Locomotor studies
      revealed that tamoxifen attenuates amphetamine-stimulated hyperactivity in rats
      but has no depressant or stimulant activity in the absence of amphetamine. These
      results suggest a complex mechanism of action for tamoxifen as a regulator of the
      DAT. Due to its effectiveness against amphetamine actions and its central nervous
      system permeant activity, the tamoxifen structure represents an excellent
      starting point for a structure-based drug-design program to develop a
      pharmacological therapeutic for psychostimulant abuse.

PMID- 30108163
TI  - Randomised placebo-controlled trial of dietary glutamine supplements for
      postinfectious irritable bowel syndrome.
AB  - BACKGROUND: More effective treatments are needed for patients with
      postinfectious, diarrhoea-predominant, irritable bowel syndrome (IBS-D).
      Accordingly, we conducted a randomised, double-blind, placebo-controlled, 8-week
      long trial to assess the efficacy and safety of oral glutamine therapy in
      patients who developed IBS-D with increased intestinal permeability following an
      enteric infection. METHODS: Eligible adults were randomised to glutamine (5
      g/t.i.d.) or placebo for 8 weeks. The primary end point was a reduction of >=50
      points on the Irritable Bowel Syndrome Severity Scoring System (IBS-SS).
      Secondary endpoints included: raw IBS-SS scores, changes in daily bowel movement
      frequency, stool form (Bristol Stool Scale) and intestinal permeability. RESULTS:
      Fifty-four glutamine and 52 placebo subjects completed the 8-week study. The
      primary endpoint occurred in 43 (79.6%) in the glutamine group and 3 (5.8%) in
      the placebo group (a 14-fold difference). Glutamine also reduced all secondary
      endpoint means: IBS-SS score at 8 weeks (301 vs 181, p<0.0001), daily bowel
      movement frequency (5.4 vs 2.9+/-1.0, p<0.0001), Bristol Stool Scale (6.5 vs 3.9,
      p<0.0001) and intestinal permeability (0.11 vs 0.05; p<0.0001). 'Intestinal
      hyperpermeability' (elevated urinary lactulose/mannitol ratios) was normalised in
      the glutamine but not the control group. Adverse events and rates of study-drug
      discontinuation were low and similar in the two groups. No serious adverse events
      were observed. CONCLUSIONS: In patients with IBS-D with intestinal
      hyperpermeability following an enteric infection, oral dietary glutamine
      supplements dramatically and safely reduced all major IBS-related endpoints.
      Large randomised clinical trials (RCTs) should now be done to validate these
      findings, assess quality of life benefits and explore pharmacological mechanisms.
      TRIAL REGISTRATION NUMBER: NCT 1414244; Results.

PMID- 30108164
TI  - Increased Genetic Instability and Accelerated Progression of Colitis-associated
      Colorectal Cancer through Intestinal Epithelium-specific Deletion of Klf4.
AB  - Kruppel-like factor 4 (KLF4), a zinc finger transcription factor, regulates
      homeostasis of the intestinal epithelium. Previously, it was reported that KLF4
      functions as a tumor suppressor in colorectal cancer. Here, evidence demonstrates
      that KLF4 mitigates the development and progression of colitis-associated
      colorectal cancer (CAC) in a murine model. Mice with intestinal epithelium
      specific deletion of Klf4 (Klf4DeltaIS ) and control mice (Klf4fl/fl ) were used
      to explore the role of KLF4 in the development of azoxymethane (AOM) and dextran
      sodium sulfate (DSS)-induced CAC. Upon AOM and DSS treatment, KLF4 expression was
      progressively lost in colonic tissues of Klf4fl/fl mice during tumor development.
      Klf4DeltaIS mice treated with AOM/DSS developed significantly more adenomatous
      polyps and carcinomas in situ in comparison with treated Klf4fl/fl mice.
      Adenomatous polyps, but not normal-appearing mucosa, from colonic tissues of
      treated Klf4DeltaIS mice contained a significantly increased number of mitotic
      cells with more than 2 centrosomes relative to treated control mice. KLF4 and p53
      colocalize to the centrosomes in mouse embryonic fibroblasts (MEF). Absence of
      KLF4 in Klf4-/- MEFs inhibits and its overexpression restores p53 localization to
      the centrosomes in Klf4-/- MEFs.Implications: Taken together, these results
      indicate that KLF4 plays a protective role against progression of CAC by guarding
      against genetic instability. Mol Cancer Res; 1-12. (c)2018 AACR.

PMID- 30108162
TI  - Molecular predictors of prevention of recurrence in HCC with sorafenib as
      adjuvant treatment and prognostic factors in the phase 3 STORM trial.
AB  - OBJECTIVE: Sorafenib is the standard systemic therapy for advanced hepatocellular
      carcinoma (HCC). Survival benefits of resection/local ablation for early HCC are
      compromised by 70% 5-year recurrence rates. The phase 3 STORM trial comparing
      sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint
      of improving recurrence-free survival (RFS). The biomarker companion study
      BIOSTORM aims to define (A) predictors of recurrence prevention with sorafenib
      and (B) prognostic factors with B level of evidence. DESIGN: Tumour tissue from
      188 patients randomised to receive sorafenib (83) or placebo (105) in the STORM
      trial was collected. Analyses included gene expression profiling, targeted exome
      sequencing (19 known oncodrivers), immunohistochemistry (pERK, pVEGFR2, Ki67),
      fluorescence in situ hybridisation (VEGFA) and immunome. A gene signature
      capturing improved RFS in sorafenib-treated patients was generated. All 70 RFS
      events were recurrences, thus time to recurrence equalled RFS. Predictive and
      prognostic value was assessed using Cox regression models and interaction test.
      RESULTS: BIOSTORM recapitulates clinicopathological characteristics of STORM.
      None of the biomarkers tested (related to angiogenesis and proliferation) or
      previously proposed gene signatures, or mutations predicted sorafenib benefit or
      recurrence. A newly generated 146-gene signature identifying 30% of patients
      captured benefit to sorafenib in terms of RFS (p of interaction=0.04). These
      sorafenib RFS responders were significantly enriched in CD4+ T, B and cytolytic
      natural killer cells, and lacked activated adaptive immune components.
      Hepatocytic pERK (HR=2.41; p=0.012) and microvascular invasion (HR=2.09; p=0.017)
      were independent prognostic factors. CONCLUSION: In BIOSTORM, only hepatocytic
      pERK and microvascular invasion predicted poor RFS. No mutation, gene
      amplification or previously proposed gene signatures predicted sorafenib benefit.
      A newly generated multigene signature associated with improved RFS on sorafenib
      warrants further validation. TRIAL REGISTRATION NUMBER: NCT00692770.

PMID- 30108165
TI  - Comprehensive Genomic Profiling of Patient-matched Head and Neck Cancer Cells: A
      Preclinical Pipeline for Metastatic and Recurrent Disease.
AB  - : Metastases and tumor recurrence have a major prognostic impact in head and neck
      squamous cell carcinoma (HNSCC); however, cellular models that comprehensively
      characterize metastatic and recurrent HNSCC are lacking. To this end, we obtained
      genomic, transcriptomic, and copy number profiles of the UM-SCC cell line panel,
      encompassing patient-matched metastatic and recurrent cells. UM-SCC cells
      recapitulate the most prevalent genomic alterations described in HNSCC, featuring
      common TP53, PI3K, NOTCH, and Hippo pathway mutations. This analysis identified a
      novel F977Y kinase domain PIK3CA mutation exclusively present in a recurrent cell
      line (UM-SCC14B), potentially conferring resistance to PI3K inhibitors. Small
      proline-rich protein 2A (SPRR2A), a protein involved in epithelial homeostasis
      and invasion, was one of the most consistently downregulated transcripts in
      metastatic and recurrent UM-SCC cells. Assessment of SPRR2A protein expression in
      a clinical cohort of patients with HNSCC confirmed common SPRR2A downregulation
      in primary tumors (61.9% of cases) and lymph node metastases (31.3%), but not in
      normal tissue. High expression of SPRR2A in lymph node metastases was, along with
      nonoropharyngeal location of the primary tumor, an independent prognostic factor
      for regional disease recurrence after surgery and radiotherapy (HR 2.81; 95% CI,
      1.16-6.79; P = 0.02). These results suggest that SPRR2A plays a dual role in
      invasion and therapeutic resistance in HNSCC, respectively through its
      downregulation and overexpression. IMPLICATIONS: The current study reveals
      translationally relevant mechanisms underlying metastasis and recurrence in HNSCC
      and represents an adjuvant tool for preclinical research in this disease setting.
      Underlining its discovery potential this approach identified a PIK3CA-resistant
      mutation as well as SPRR2A as possible theragnostic markers.

PMID- 30108166
TI  - The Persistence-Inducing Toxin HokB Forms Dynamic Pores That Cause ATP Leakage.
AB  - Bacterial populations harbor a small fraction of cells that display transient
      multidrug tolerance. These so-called persister cells are extremely difficult to
      eradicate and contribute to the recalcitrance of chronic infections. Several
      signaling pathways leading to persistence have been identified. However, it is
      poorly understood how the effectors of these pathways function at the molecular
      level. In a previous study, we reported that the conserved GTPase Obg induces
      persistence in Escherichia coli via transcriptional upregulation of the toxin
      HokB. In the present study, we demonstrate that HokB inserts in the cytoplasmic
      membrane where it forms pores. The pore-forming capacity of the HokB peptide is
      demonstrated by in vitro conductance measurements on synthetic and natural lipid
      bilayers, revealing an asymmetrical conductance profile. Pore formation is
      directly linked to persistence and results in leakage of intracellular ATP. HokB
      induced persistence is strongly impeded in the presence of a channel blocker,
      thereby providing a direct link between pore functioning and persistence.
      Furthermore, the activity of HokB pores is sensitive to the membrane potential.
      This sensitivity presumably results from the formation of either intermediate or
      mature pore types depending on the membrane potential. Taken together, these
      results provide a detailed view on the mechanistic basis of persister formation
      through the effector HokB.IMPORTANCE There is increasing awareness of the
      clinical importance of persistence. Indeed, persistence is linked to the
      recalcitrance of chronic infections, and evidence is accumulating that persister
      cells constitute a pool of viable cells from which resistant mutants can emerge.
      Unfortunately, persistence is a poorly understood process at the mechanistic
      level. In this study, we unraveled the pore-forming activity of HokB in E. coli
      and discovered that these pores lead to leakage of intracellular ATP, which is
      correlated with the induction of persistence. Moreover, we established a link
      between persistence and pore activity, as the number of HokB-induced persister
      cells was strongly reduced using a channel blocker. The latter opens
      opportunities to reduce the number of persister cells in a clinical setting.

PMID- 30108167
TI  - Novel Autotrophic Organisms Contribute Significantly to the Internal Carbon
      Cycling Potential of a Boreal Lake.
AB  - Oxygen-stratified lakes are typical for the boreal zone and also a major source
      of greenhouse gas emissions in the region. Due to shallow light penetration,
      restricting the growth of phototrophic organisms, and large allochthonous organic
      carbon inputs from the catchment area, the lake metabolism is expected to be
      dominated by heterotrophic organisms. In this study, we test this assumption and
      show that the potential for autotrophic carbon fixation and internal carbon
      cycling is high throughout the water column. Further, we show that during the
      summer stratification carbon fixation can exceed respiration in a boreal lake
      even below the euphotic zone. Metagenome-assembled genomes and 16S profiling of a
      vertical transect of the lake revealed multiple organisms in an oxygen-depleted
      compartment belonging to novel or poorly characterized phyla. Many of these
      organisms were chemolithotrophic, potentially deriving their energy from
      reactions related to sulfur, iron, and nitrogen transformations. The community,
      as well as the functions, was stratified along the redox gradient. The
      autotrophic potential in the lake metagenome below the oxygenic zone was high,
      pointing toward a need for revising our concepts of internal carbon cycling in
      boreal lakes. Further, the importance of chemolithoautotrophy for the internal
      carbon cycling suggests that many predicted climate change-associated
      fluctuations in the physical properties of the lake, such as altered mixing
      patterns, likely have consequences for the whole-lake metabolism even beyond the
      impact to the phototrophic community.IMPORTANCE Autotrophic organisms at the base
      of the food web are the only life form capable of turning inorganic carbon into
      the organic form, facilitating the survival of all other organisms. In certain
      environments, the autotrophic production is limited by environmental conditions
      and the food web is supported by external carbon inputs. One such environment is
      stratified boreal lakes, which are one of the biggest natural sources of
      greenhouse gas emissions in the boreal region. Thus, carbon cycling in these
      habitats is of utmost importance for the future climate. Here, we demonstrate a
      high potential for internal carbon cycling via phototrophic and novel
      chemolithotrophic organisms in the anoxic, poorly illuminated layers of a boreal
      lake. Our results significantly increase our knowledge on the microbial
      communities and their metabolic potential in oxygen-depleted freshwaters and help
      to understand and predict how climate change-induced alterations could impact the
      lake carbon dynamics.

PMID- 30108168
TI  - Nitric Oxide Disrupts Zinc Homeostasis in Salmonella enterica Serovar
      Typhimurium.
AB  - Nitric oxide (NO.) produced by mammalian cells exerts antimicrobial actions that
      result primarily from the modification of protein thiols (S-nitrosylation) and
      metal centers. A comprehensive approach was used to identify novel targets of NO.
      in Salmonella enterica serovar Typhimurium (S. Typhimurium). Newly identified
      targets include zinc metalloproteins required for DNA replication and repair
      (DnaG, PriA, and TopA), protein synthesis (AlaS and RpmE), and various metabolic
      activities (ClpX, GloB, MetE, PepA, and QueC). The cytotoxic actions of free zinc
      are mitigated by the ZntA and ZitB zinc efflux transporters, which are required
      for S. Typhimurium resistance to zinc overload and nitrosative stress in vitro
      Zinc efflux also ameliorates NO.-dependent zinc mobilization following
      internalization by activated macrophages and is required for virulence in NO.
      producing mice, demonstrating that host-derived NO. causes zinc stress in
      intracellular bacteria.IMPORTANCE Nitric oxide (NO.) is produced by macrophages
      in response to inflammatory stimuli and restricts the growth of intracellular
      bacteria. Mechanisms of NO.-dependent antimicrobial actions are incompletely
      understood. Here, we show that zinc metalloproteins are important targets of NO.
      in Salmonella, including the DNA replication proteins DnaG and PriA, which were
      hypothesized to be NO. targets in earlier studies. Like iron, zinc is a cofactor
      for several essential proteins but is toxic at elevated concentrations. This
      study demonstrates that NO. mobilizes free zinc in Salmonella and that specific
      efflux transporters ameliorate the cytotoxic effects of free zinc during
      infection.

PMID- 30108169
TI  - Adhesion of Staphylococcus aureus to Corneocytes from Atopic Dermatitis Patients
      Is Controlled by Natural Moisturizing Factor Levels.
AB  - The bacterial pathogen Staphylococcus aureus plays an important role in atopic
      dermatitis (AD), a chronic disorder that mostly affects children. Colonization of
      the skin of AD patients by S. aureus exacerbates the disease, but the molecular
      determinants of the bacterium-skin adhesive interactions are poorly understood.
      Specifically, reduced levels of natural moisturizing factor (NMF) in the stratum
      corneum have been shown to be associated with more severe AD symptoms, but
      whether this is directly related to S. aureus adhesion is still an open question.
      Here, we demonstrate a novel relationship between NMF expression in AD skin and
      strength of bacterial adhesion. Low-NMF corneocytes, unlike high-NMF ones, are
      covered by a dense layer of nanoscale villus protrusions. S. aureus bacteria
      isolated from AD skin bind much more strongly to corneocytes when the NMF level
      is reduced. Strong binding forces originate from a specific interaction between
      the bacterial adhesion clumping factor B (ClfB) and skin ligands. Remarkably,
      mechanical tension dramatically strengthens ClfB-mediated adhesion, as observed
      with catch bonds, demonstrating that physical stress plays a role in promoting
      colonization of AD skin by S. aureus Collectively, our findings demonstrate that
      patient NMF levels regulate the strength of S. aureus-corneocyte adhesion, the
      first step in skin colonization, and suggest that the ClfB binding mechanism
      could represent a potential target for new therapeutic treatments.IMPORTANCE
      Bacterium-skin interactions play important roles in skin disorders, yet their
      molecular details are poorly understood. In this study, we decipher the molecular
      forces at play during adhesion of Staphylococcus aureus to skin corneocytes in
      the clinically important context of atopic dermatitis (AD), also known as eczema.
      We identify a unique relationship between the level of natural moisturizing
      factor (NMF) in the skin and the strength of bacterium-corneocyte adhesion.
      Bacterial adhesion is primarily mediated by the surface protein clumping factor B
      (ClfB) and is enhanced by physical stress, highlighting the role of protein
      mechanobiology in skin colonization. Similar to a catch bond behavior, this
      mechanism represents a promising target for the development of novel
      antistaphylococcal agents.

PMID- 30108170
TI  - Developmental Dynamics of Long Noncoding RNA Expression during Sexual Fruiting
      Body Formation in Fusarium graminearum.
AB  - Long noncoding RNA (lncRNA) plays important roles in sexual development in
      eukaryotes. In filamentous fungi, however, little is known about the expression
      and roles of lncRNAs during fruiting body formation. By profiling developmental
      transcriptomes during the life cycle of the plant-pathogenic fungus Fusarium
      graminearum, we identified 547 lncRNAs whose expression was highly dynamic, with
      about 40% peaking at the meiotic stage. Many lncRNAs were found to be antisense
      to mRNAs, forming 300 sense-antisense pairs. Although small RNAs were produced
      from these overlapping loci, antisense lncRNAs appeared not to be involved in
      gene silencing pathways. Genome-wide analysis of small RNA clusters identified
      many silenced loci at the meiotic stage. However, we found transcriptionally
      active small RNA clusters, many of which were associated with lncRNAs. Also, we
      observed that many antisense lncRNAs and their respective sense transcripts were
      induced in parallel as the fruiting bodies matured. The nonsense-mediated decay
      (NMD) pathway is known to determine the fates of lncRNAs as well as mRNAs. Thus,
      we analyzed mutants defective in NMD and identified a subset of lncRNAs that were
      induced during sexual development but suppressed by NMD during vegetative growth.
      These results highlight the developmental stage-specific nature and functional
      potential of lncRNA expression in shaping the fungal fruiting bodies and provide
      fundamental resources for studying sexual stage-induced
      lncRNAs.IMPORTANCEFusarium graminearum is the causal agent of the head blight on
      our major staple crops, wheat and corn. The fruiting body formation on the host
      plants is indispensable for the disease cycle and epidemics. Long noncoding RNA
      (lncRNA) molecules are emerging as key regulatory components for sexual
      development in animals and plants. To date, however, there is a paucity of
      information on the roles of lncRNAs in fungal fruiting body formation. Here we
      characterized hundreds of lncRNAs that exhibited developmental stage-specific
      expression patterns during fruiting body formation. Also, we discovered that many
      lncRNAs were induced in parallel with their overlapping transcripts on the
      opposite DNA strand during sexual development. Finally, we found a subset of
      lncRNAs that were regulated by an RNA surveillance system during vegetative
      growth. This research provides fundamental genomic resources that will spur
      further investigations on lncRNAs that may play important roles in shaping fungal
      fruiting bodies.

PMID- 30108171
TI  - Inhibition of EGFR Signaling Protects from Mucormycosis.
AB  - Mucormycosis is a life-threatening, invasive fungal infection that is caused by
      various species belonging to the order Mucorales. Rhizopus species are the most
      common cause of the disease, responsible for approximately 70% of all cases of
      mucormycosis. During pulmonary mucormycosis, inhaled Rhizopus spores must adhere
      to and invade airway epithelial cells in order to establish infection. The
      molecular mechanisms that govern this interaction are poorly understood. We
      performed an unbiased survey of the host transcriptional response during early
      stages of Rhizopus arrhizus var. delemar (R. delemar) infection in a murine model
      of pulmonary mucormycosis using transcriptome sequencing (RNA-seq). Network
      analysis revealed activation of the host's epidermal growth factor receptor
      (EGFR) signaling. Consistent with the RNA-seq results, EGFR became phosphorylated
      upon in vitro infection of human alveolar epithelial cells with several members
      of the Mucorales, and this phosphorylated, activated form of EGFR colocalized
      with R. delemar spores. Inhibition of EGFR signaling with cetuximab or gefitinib,
      specific FDA-approved inhibitors of EGFR, significantly reduced the ability of R.
      delemar to invade and damage airway epithelial cells. Furthermore, gefitinib
      treatment significantly prolonged survival of mice with pulmonary mucormycosis,
      reduced tissue fungal burden, and attenuated the activation of EGFR in response
      to pulmonary mucormycosis. These results indicate EGFR represents a novel host
      target to block invasion of alveolar epithelial cells by R. delemar, and
      inhibition of EGFR signaling provides a novel approach for treating mucormycosis
      by repurposing an FDA-approved drug.IMPORTANCE Mucormycosis is an increasingly
      common, highly lethal fungal infection with very limited treatment options. Using
      a combination of in vivo animal models, transcriptomics, cell biology, and
      pharmacological approaches, we have demonstrated that Mucorales fungi activate
      EGFR signaling to induce fungal uptake into airway epithelial cells. Inhibition
      of EGFR signaling with existing FDA-approved drugs significantly increased
      survival following R. arrhizus var. delemar infection in mice. This study
      enhances our understanding of how Mucorales fungi invade host cells during the
      establishment of pulmonary mucormycosis and provides a proof-of-concept for the
      repurposing of FDA-approved drugs that target EGFR function.

PMID- 30108173
TI  - Elastin is heterogeneously cross-linked.
AB  - Elastin is an essential vertebrate protein responsible for the elasticity of
      force-bearing tissues such as those of the lungs, blood vessels, and skin. One of
      the key features required for the exceptional properties of this durable
      biopolymer is the extensive covalent cross-linking between domains of its monomer
      molecule tropoelastin. To date, elastin's exact molecular assembly and mechanical
      properties are poorly understood. Here, using bovine elastin, we investigated the
      different types of cross-links in mature elastin to gain insight into its
      structure. We purified and proteolytically cleaved elastin from a single tissue
      sample into soluble cross-linked and noncross-linked peptides that we studied by
      high-resolution MS. This analysis enabled the elucidation of cross-links and
      other elastin modifications. We found that the lysine residues within the
      tropoelastin sequence were simultaneously unmodified and involved in various
      types of cross-links with different other domains. The Lys-Pro domains were
      almost exclusively linked via lysinonorleucine, whereas Lys-Ala domains were
      found to be cross-linked via lysinonorleucine, allysine aldol, and desmosine.
      Unexpectedly, we identified a high number of intramolecular cross-links between
      lysine residues in close proximity. In summary, we show on the molecular level
      that elastin formation involves random cross-linking of tropoelastin monomers
      resulting in an unordered network, an unexpected finding compared with previous
      assumptions of an overall beaded structure.

PMID- 30108172
TI  - Exposure to Arsenite in CD-1 Mice during Juvenile and Adult Stages: Effects on
      Intestinal Microbiota and Gut-Associated Immune Status.
AB  - Intestinal microbiota composition and gut-associated immune response can
      contribute to the toxicity of arsenic. We investigated the potential toxicity of
      short-term arsenic exposure on gut microbiome composition, intestinal immune
      status, microbial arsenic resistance gene, and arsenic metabolic profiles in
      adult and developmental stages of CD-1 mice. The potential toxicity of arsenite
      [As(III)] was determined for two life stages: (i) adult animals at 24 or 48 h
      after single gavage (0.05 mg/kg body weight [b.w.] [low dose], 0.1 mg/kg b.w.
      [medium dose], and 0.2 mg/kg b.w. [high dose]) and repeated exposure at 1
      mg/liter for 8 days and (ii) postnatal day 10 (PND10) and PND21 after single
      gavage (0.05 mg/kg b.w.). Dose- and time-dependent responses in bacterial
      recovery/microbial composition were observed in adults after a single gavage.
      Repeated exposure caused a transient decrease in the recovery of intestinal
      bacteria, a shift in the bacterial population with abundance of arsenic
      resistance genes, and evidence for host metabolism of arsenite into less-reactive
      trivalent methylated species. Arsenic exposure in adult animals induced high
      levels of CC chemokines and of proinflammatory and anti-inflammatory cytokine
      secretion in intestine. Arsenic exposure at PND21 resulted in the development of
      distinct bacterial populations. Results of this study highlight significant
      changes in the intestinal microbiome and gut-associated immune status during a
      single or repeated exposure to arsenic in juvenile and adult animals. The data
      warrant investigation of the long-term effects of oral arsenic exposure on the
      microbiome and of immune system development and responses.IMPORTANCE
      Transformation of organic arsenic to toxic inorganic arsenic (iAs) is likely
      carried out by intestinal bacteria, and iAs may alter the viability of certain
      microbial populations. This study addressed the impact of arsenic exposure on
      intestinal microbiota diversity and host gut-associated immune mediators during
      early development or adulthood using scenarios of acute or repeated doses. During
      acute arsenic exposure, animals developed defense functions characterized by
      higher abundances of bacteria that are involved in arsenic resistance or
      detoxification mechanisms. Arsenite had a negative effect on the abundance of
      bacterial species that are involved in the conversion of protein to butyrate,
      which is an alternative energy source in the intestine. The intestinal mucosal
      immune cytokine profile reflected a mechanism of protection from arsenic
      toxicity.

PMID- 30108174
TI  - LEM domain-containing protein 3 antagonizes TGFbeta-SMAD2/3 signaling in a
      stiffness-dependent manner in both the nucleus and cytosol.
AB  - Transforming growth factor-beta (TGFbeta) signaling through SMAD2/3 is an
      important driver of pathological fibrosis in multiple organ systems. TGFbeta
      signaling and extracellular matrix (ECM) stiffness form an unvirtuous
      pathological circuit in which matrix stiffness drives activation of latent
      TGFbeta, and TGFbeta signaling then drives cellular stress and ECM synthesis.
      Moreover, ECM stiffness also appears to sensitize cells to exogenously activated
      TGFbeta through unknown mechanisms. Here, using human fibroblasts, we explored
      the effect of ECM stiffness on a putative inner nuclear membrane protein, LEM
      domain-containing protein 3 (LEMD3), which is physically connected to the cell's
      actin cytoskeleton and inhibits TGFbeta signaling. We showed that LEMD3-SMAD2/3
      interactions are inversely correlated with ECM stiffness and TGFbeta-driven
      luciferase activity and that LEMD3 expression is correlated with the mechanical
      response of the TGFbeta-driven luciferase reporter. We found that actin
      polymerization but not cellular stress or LEMD3-nuclear-cytoplasmic couplings
      were necessary for LEMD3-SMAD2/3 interactions. Intriguingly, LEMD3 and SMAD2/3
      frequently interacted in the cytosol, and we discovered LEMD3 was proteolytically
      cleaved into protein fragments. We confirmed that a consensus C-terminal LEMD3
      fragment binds SMAD2/3 in a stiffness-dependent manner throughout the cell and is
      sufficient for antagonizing SMAD2/3 signaling. Using human lung biopsies, we
      observed that these nuclear and cytosolic interactions are also present in tissue
      and found that fibrotic tissues exhibit locally diminished and cytoplasmically
      shifted LEMD3-SMAD2/3 interactions, as noted in vitro Our work reveals novel
      LEMD3 biology and stiffness-dependent regulation of TGFbeta by LEMD3, providing a
      novel target to antagonize pathological TGFbeta signaling.

PMID- 30108175
TI  - HGF-induced formation of the MET-AXL-ELMO2-DOCK180 complex promotes RAC1
      activation, receptor clustering, and cancer cell migration and invasion.
AB  - The MET proto-oncogene-encoded receptor tyrosine kinase (MET) and AXL receptor
      tyrosine kinase (AXL) are independently operating receptor tyrosine kinases
      (RTKs) that are functionally associated with aggressive and invasive cancer cell
      growth. However, how MET and AXL regulate the migratory properties of cancer
      cells remains largely unclear. We report here that the addition of hepatocyte
      growth factor (HGF), the natural ligand of MET, to serum-starved human
      glioblastoma cells induces the rapid activation of both MET and AXL and formation
      of highly polarized MET-AXL clusters on the plasma membrane. HGF also promoted
      the formation of the MET and AXL protein complexes and phosphorylation of AXL,
      independent of AXL's ligand, growth arrest-specific 6 (GAS6). The HGF-induced MET
      AXL complex stimulated rapid and dynamic cytoskeleton reorganization by
      activating the small GTPase RAC1, a process requiring both MET and AXL kinase
      activities. We further found that HGF also promotes the recruitment of ELMO2 and
      DOCK180, a bipartite guanine nucleotide exchange factor for RAC1, to the MET-AXL
      complex and thereby stimulates the RAC1-dependent cytoskeleton reorganization. We
      also demonstrated that the MET-AXL-ELMO2-DOCK180 complex is critical for HGF
      induced cell migration and invasion in glioblastoma or other cancer cells. Our
      findings uncover a critical HGF-dependent signaling pathway that involves the
      assembly of a large protein complex consisting of MET, AXL, ELMO2, and DOCK180 on
      the plasma membrane, leading to RAC1-dependent cell migration and invasion in
      various cancer cells.

PMID- 30108177
TI  - Effects of polyamines on protein synthesis and growth of Escherichia coli.
AB  - The polyamines (PA) putrescine, spermidine, and spermine have numerous roles in
      the growth of both prokaryotic and eukaryotic cells. For example, it is well
      known that putrescine and spermidine are strongly involved in proliferation and
      viability of Escherichia coli cells. Studies of polyamine functions and
      distributions in E. coli cells have revealed that polyamines mainly exist as an
      RNA-polyamine complex. Polyamines stimulate the assembly of 30S ribosomal
      subunits and thereby increase general protein synthesis 1.5- to 2.0-fold.
      Moreover, these studies have shown that polyamines stimulate synthesis of 20
      different proteins at the level of translation, which are strongly involved in
      cell growth and viability. The genes encoding these 20 different proteins were
      termed as the "polyamine modulon." We here review the mechanism of activation of
      30S ribosomal subunits and stimulation of specific proteins. Other functions of
      polyamines in E. coli are also described.

PMID- 30108176
TI  - Uropathogenic enterobacteria use the yersiniabactin metallophore system to
      acquire nickel.
AB  - Invasive Gram-negative bacteria often express multiple virulence-associated metal
      ion chelators to combat host-mediated metal deficiencies. Escherichia coli,
      Klebsiella, and Yersinia pestis isolates encoding the Yersinia high pathogenicity
      island (HPI) secrete yersiniabactin (Ybt), a metallophore originally shown to
      chelate iron ions during infection. However, our recent demonstration that Ybt
      also scavenges copper ions during infection led us to question whether it might
      be capable of retrieving other metals as well. Here, we find that uropathogenic
      E. coli also use Ybt to bind extracellular nickel ions. Using quantitative MS, we
      show that the canonical metal-Ybt import pathway internalizes the resulting Ni
      Ybt complexes, extracts the nickel, and releases metal-free Ybt back to the
      extracellular space. We find that E. coli and Klebsiella direct the nickel
      liberated from this pathway to intracellular nickel enzymes. Thus, Ybt may
      provide access to nickel that is inaccessible to the conserved NikABCDE permease
      system. Nickel should be considered alongside iron and copper as a plausible
      substrate for Ybt-mediated metal import by enterobacteria during human
      infections.

PMID- 30108178
TI  - Highly efficient cellular uptake of a cell-penetrating peptide (CPP) derived from
      the capsid protein of porcine circovirus type 2.
AB  - Porcine circovirus type 2 (PCV2) is one of the smallest, nonenveloped, single
      stranded DNA viruses. The PCV2 capsid protein (Cap) is the sole viral structural
      protein and main antigenic determinant. Previous sequence analysis has revealed
      that the N terminus of the PCV2 Cap contains a nuclear localization signal (NLS)
      enriched in positively charged residues. Here, we report that PCV2's NLS can
      function as a cell-penetrating peptide (CPP). We observed that this NLS can carry
      macromolecules, e.g. enhanced GFP (EGFP), into cells when they are fused to the
      NLS, indicating that it can function as a CPP, similar to the classical CPP
      derived from HIV type 1 transactivator of transcription protein (HIV TAT). We
      also found that the first 17 residues of the NLS (NLS-A) have a key role in
      cellular uptake. In addition to entering cells via multiple endocytic processes,
      NLS-A was also rapidly internalized via direct translocation enabled by increased
      membrane permeability and was evenly distributed throughout cells when its
      concentration in cell cultures was >=10 MUm Of note, cellular NLS-A uptake was
      ~10 times more efficient than that of HIV TAT. We inferred that the externalized
      NLS of the PCV2 Cap may accumulate to a high concentration (>=10 MUm) at a local
      membrane area, increasing membrane permeability to facilitate viral entry into
      the cell to release its genome into a viral DNA reproduction center. We conclude
      that NLS-A has potential as a versatile vehicle for shuttling foreign molecules
      into cells, including pharmaceuticals for therapeutic interventions.

PMID- 30108179
TI  - Human proteins that interact with RNA/DNA hybrids.
AB  - RNA/DNA hybrids form when RNA hybridizes with its template DNA generating a three
      stranded structure known as the R-loop. Knowledge of how they form and resolve,
      as well as their functional roles, is limited. Here, by pull-down assays followed
      by mass spectrometry, we identified 803 proteins that bind to RNA/DNA hybrids.
      Because these proteins were identified using in vitro assays, we confirmed that
      they bind to R-loops in vivo. They include proteins that are involved in a
      variety of functions, including most steps of RNA processing. The proteins are
      enriched for K homology (KH) and helicase domains. Among them, more than 300
      proteins preferred binding to hybrids than double-stranded DNA. These proteins
      serve as starting points for mechanistic studies to elucidate what RNA/DNA
      hybrids regulate and how they are regulated.

PMID- 30108180
TI  - Natural genetic variation in C. elegans identified genomic loci controlling
      metabolite levels.
AB  - Metabolic homeostasis is sustained by complex biological networks that respond to
      nutrient availability. Genetic and environmental factors may disrupt this
      equilibrium, leading to metabolic disorders, including obesity and type 2
      diabetes. To identify the genetic factors controlling metabolism, we performed
      quantitative genetic analysis using a population of 199 recombinant inbred lines
      (RILs) in the nematode Caenorhabditis elegans We focused on the genomic regions
      that control metabolite levels by measuring fatty acid (FA) and amino acid (AA)
      composition in the RILs using targeted metabolomics. The genetically diverse RILs
      showed a large variation in their FA and AA levels with a heritability ranging
      from 32% to 82%. We detected strongly co-correlated metabolite clusters and 36
      significant metabolite quantitative trait loci (mQTL). We focused on mQTL
      displaying highly significant linkage and heritability, including an mQTL for the
      FA C14:1 on Chromosome I, and another mQTL for the FA C18:2 on Chromosome IV.
      Using introgression lines (ILs), we were able to narrow down both mQTL to a 1.4
      Mbp and a 3.6-Mbp region, respectively. RNAi-based screening focusing on the
      Chromosome I mQTL identified several candidate genes for the C14:1 mQTL,
      including lagr-1, Y87G2A.2, nhr-265, nhr-276, and nhr-81 Overall, this systems
      approach provides us with a powerful platform to study the genetic basis of C.
      elegans metabolism. Furthermore, it allows us to investigate interventions such
      as nutrients and stresses that maintain or disturb the regulatory network
      controlling metabolic homeostasis, and identify gene-by-environment interactions.

PMID- 30108181
TI  - Identification of Toll-like receptor signaling inhibitors based on selective
      activation of hierarchically acting signaling proteins.
AB  - Toll-like receptors (TLRs) recognize various pathogen- and host tissue-derived
      molecules and initiate inflammatory immune responses. Exaggerated or prolonged
      TLR activation, however, can lead to etiologically diverse diseases, such as
      bacterial sepsis, metabolic and autoimmune diseases, or stroke. Despite the
      apparent medical need, no small-molecule drugs against TLR pathways are
      clinically available. This may be because of the complex signaling mechanisms of
      TLRs, which are governed by a series of protein-protein interactions initiated by
      Toll/interleukin-1 receptor homology domains (TIR) found in TLRs and the
      cytoplasmic adaptor proteins TIRAP and MyD88. Oligomerization of TLRs with MyD88
      or TIRAP leads to the recruitment of members of the IRAK family of kinases and
      the E3 ubiquitin ligase TRAF6. We developed a phenotypic drug screening system
      based on the inducible homodimerization of either TIRAP, MyD88, or TRAF6, that
      ranked hits according to their hierarchy of action. From a bioactive compound
      library, we identified methyl-piperidino-pyrazole (MPP) as a TLR-specific
      inhibitor. Structure-activity relationship analysis, quantitative proteomics,
      protein-protein interaction assays, and cellular thermal shift assays suggested
      that MPP targets the TIR domain of MyD88. Chemical evolution of the original MPP
      scaffold generated compounds with selectivity for distinct TLRs that interfered
      with specific TIR interactions. Administration of an MPP analog to mice protected
      them from TLR4-dependent inflammation. These results validate this phenotypic
      screening approach and suggest that the MPP scaffold could serve as a starting
      point for the development of anti-inflammatory drugs.

PMID- 30108183
TI  - Aurora-PLK1 cascades as key signaling modules in the regulation of mitosis.
AB  - Mitosis is controlled by reversible protein phosphorylation involving specific
      kinases and phosphatases. A handful of major mitotic protein kinases, such as the
      cyclin B-CDK1 complex, the Aurora kinases, and Polo-like kinase 1 (PLK1),
      cooperatively regulate distinct mitotic processes. Research has identified
      proteins and mechanisms that integrate these kinases into signaling cascades that
      guide essential mitotic events. These findings have important implications for
      our understanding of the mechanisms of mitotic regulation and may advance the
      development of novel antimitotic drugs. We review collected evidence that in
      vertebrates, the Aurora kinases serve as catalytic subunits of distinct complexes
      formed with the four scaffold proteins Bora, CEP192, INCENP, and TPX2, which we
      deem "core" Aurora cofactors. These complexes and the Aurora-PLK1 cascades
      organized by Bora, CEP192, and INCENP control crucial aspects of mitosis and all
      pathways of spindle assembly. We compare the mechanisms of Aurora activation in
      relation to the different spindle assembly pathways and draw a functional analogy
      between the CEP192 complex and the chromosomal passenger complex that may reflect
      the coevolution of centrosomes, kinetochores, and the actomyosin cleavage
      apparatus. We also analyze the roles and mechanisms of Aurora-PLK1 signaling in
      the cell and centrosome cycles and in the DNA damage response.

PMID- 30108182
TI  - Mitotic phosphorylation regulates Hsp72 spindle localization by uncoupling ATP
      binding from substrate release.
AB  - Hsp72 is a member of the 70-kDa heat shock family of molecular chaperones
      (Hsp70s) that comprise a nucleotide-binding domain (NBD) and a substrate-binding
      domain (SBD) connected by a linker that couples the exchange of adenosine
      diphosphate (ADP) for adenosine triphosphate (ATP) with the release of the
      protein substrate. Mitotic phosphorylation of Hsp72 by the kinase NEK6 at Thr66
      located in the NBD promotes the localization of Hsp72 to the mitotic spindle and
      is required for efficient spindle assembly and chromosome congression and
      segregation. We determined the crystal structure of the Hsp72 NBD containing a
      genetically encoded phosphoserine at position 66. This revealed structural
      changes that stabilized interactions between subdomains within the NBD. ATP
      binding to the NBD of unmodified Hsp72 resulted in the release of substrate from
      the SBD, but phosphorylated Hsp72 retained substrate in the presence of ATP.
      Mutations that prevented phosphorylation-dependent subdomain interactions
      restored the connection between ATP binding and substrate release. Thus,
      phosphorylation of Thr66 is a reversible mechanism that decouples the allosteric
      connection between nucleotide binding and substrate release, providing further
      insight into the regulation of the Hsp70 family. We propose that phosphorylation
      of Hsp72 on Thr66 by NEK6 during mitosis promotes its localization to the spindle
      by stabilizing its interactions with components of the mitotic spindle.

PMID- 30108185
TI  - Inner Workings: Safer opioids may be on the horizon, but mitigating addiction is
      a long shot.

PMID- 30108184
TI  - Functional coupling of GABAA/B receptors and the channel TRPV4 mediates rapid
      progesterone signaling in the oviduct.
AB  - The molecular mechanism by which progesterone (P4) modulates the transport of ova
      and embryos along the oviduct is not fully resolved. We report a rapid response
      to P4 and agonists of gamma-aminobutyric acid receptors A and B (GABAA/B) in the
      mouse oviduct that was characterized by oscillatory Ca2+ signals and increased
      ciliary beat frequency (CBF). Pharmacological manipulation, genetic ablation, and
      siRNA-mediated knockdown in oviductal cells, as well as overexpression
      experiments in HEK 293T cells, confirmed the participation of the cationic
      channel TRPV4, different subunits of GABAA (alpha1 to alpha3, beta2, and beta3),
      and GABAB1 in P4-induced responses. TRPV4-mediated Ca2+ entry in close proximity
      to the inositol trisphosphate receptor was required to initiate and maintain Ca2+
      oscillations after P4 binding to GABAA and transactivation of Gi/o protein
      coupled GABAB receptors. Coimmunoprecipitation experiments and imaging of native
      tissue and HEK 293T cells demonstrated the close association of GABAA and GABAB1
      receptors and the activation of Gi/o proteins in response to P4 and GABA receptor
      agonists, confirming a molecular mechanism in which P4 and GABAergic agonists
      cooperatively stimulate cilial beating.

PMID- 30108186
TI  - Core Concept: How does climate change influence extreme weather? Impact
      attribution research seeks answers.

PMID- 30108188
TI  - A Comparison of Image Quality Using Radial vs Femoral Approaches in Patients
      Undergoing Diagnostic Coronary Angiography.
AB  - INTRODUCTION: Radial access for diagnostic coronary angiography (CAG) has gained
      traction in recent years over the femoral artery approach, but difference in
      image quality has not been extensively studied. This study aims to compare image
      quality and diagnostic value in radial vs femoral access in patients undergoing
      invasive CAG. METHODS: This is a retrospective study of 200 patients (100 radial
      and 100 femoral) undergoing CAG at an experienced center from 2014 to 2015. The
      primary endpoint was angiographic image quality, and secondary endpoints were
      proportion of non-diagnostic images and patient radiation dose. Image quality was
      assessed by four experienced angiographers using a quantitative scale. Mean
      differences in scores were compared as well as proportion of non-diagnostic
      images produced. RESULTS: Radial access produced images that were significantly
      poorer than femoral access when viewing the left coronary artery (2.65 +/- 0.04
      vs 2.79 +/- 0.03; P<.01). This difference remained significant after adjusting
      for age, gender, and catheter size (P=.04). There was no significant difference
      in image quality between the radial and femoral group when viewing the right
      coronary artery (2.91 +/- 0.03 vs 2.84 +/- 0.04; P=.11). There was a higher
      proportion of non-diagnostic images produced by radial access than femoral (3.23%
      vs 2.02%; P<.01) and radial access resulted in higher patient radiation doses
      (832.81 +/- 49.59 mGy vs 645.69 +/- 35.46 mGy; P<.01). CONCLUSION: Radial access
      produces poorer angiographic image quality and exposes patients to greater
      radiation compared to femoral access in contemporary practice. An awareness of
      these limitations is important when selecting mode of access in patients
      undergoing diagnostic CAG.

PMID- 30108189
TI  - Treatment of Drug-Eluting Stent In-Stent Restenosis With Drug-Eluting Balloons: A
      Systematic Review and Meta-Analysis.
AB  - OBJECTIVE: To evaluate the efficacy of drug-coated balloon (DEB) for the
      treatment of drug-eluting stent (DES) in-stent restenosis (ISR). METHODS: A
      comprehensive literature search was performed. The primary outcome was the
      composite of death, myocardial infarction (MI), and target-lesion
      revascularization (TLR) at longest available follow-up (range, 12-36 months).
      Outcomes for DEB vs balloon angioplasty (BA) and DEB vs DES were analyzed
      separately using a random-effect Mantel-Haenszel model, as per an a priori
      protocol. RESULTS: The study cohort comprised 1526 patients (746 DEB, 537 DES,
      243 BA). DEB was associated with lower composite outcome compared with BA alone
      (19% vs 47%; risk ratio [RR], 0.31; 95% confidence interval [CI], 0.11-0.84;
      P=.02), driven primarily by lower TLR (17% vs 34%; RR, 0.66; 95% CI, 0.46-0.95;
      P=.03), with no difference in death or MI. There was no difference in the
      composite outcome between DEB and DES (20% vs 17%; RR, 1.2; 95% CI, 0.82-1.74;
      P=.35); DEB was associated with higher TLR (17.4% vs 11.3%; RR, 1.48; 95% CI,
      1.08-2.03; P=.01), but lower all-cause mortality (2.2% vs 5.7%; RR, 0.43; 95% CI,
      0.22-0.82; P=.01), with no difference in MI or stent thrombosis. CONCLUSIONS: DEB
      was associated with a lower TLR rate than BA alone, but associated with a higher
      TLR rate than implantation of another DES. However, additional DES use was
      associated with an increase in mortality, a finding that requires further
      investigation.

PMID- 30108190
TI  - Feasibility of Transradial Access for Coronary Interventions Via Percutaneous
      Angioplasty of the Radial Artery in Cases of Functional Radial Occlusion.
AB  - AIMS: Transradial access (TRA) has become a standard approach for cardiac
      catheterization. However, an obstacle to TRA is the risk of radial artery
      occlusion (RAO) after radial access in about 5%-10% of patients. We analyzed the
      safety and efficacy of getting vascular access after RAO by percutaneous
      transluminal angioplasty in cases of chronic radial occlusion. METHODS AND
      RESULTS: Chronic RAO was confirmed by Allen test and color Doppler in 8 patients.
      TRA was achieved by puncture in the distal tabatiere (anatomical snuffbox) using
      Seldinger's technique followed by insertion of a 5 Fr radial introducer sheath.
      Angiogram was obtained before percutaneous transluminal angioplasty with a 2.0 mm
      coronary balloon to reopen the artery. Puncture of the occluded radial artery,
      percutaneous transluminal angioplasty, and subsequent coronary catheterization
      and PCI were successful in all 8 patients. One complication was a dissection of
      the radial artery without further adverse events. No hemorrhage or compartment
      syndrome occurred. CONCLUSIONS: With increased application of TRA, the incidence
      of RAO is also rising. Some patients with RAO require repeat cardiac
      catheterization. Given the risk of damaging the contralateral radial artery in
      subsequent procedures, using the same access site is desirable. We demonstrate
      that it is feasible to get access to an occluded radial artery by percutaneous
      transluminal angioplasty.

PMID- 30108192
TI  - A new editor of the JCI.
AB  - This issue of the Journal of Clinical Investigation marks the transition of the
      position of editor from Gordon Tomaselli to me. It is with great humility that I
      begin my tenure as the editor of the flagship journal of the American Society for
      Clinical Investigation (ASCI). On behalf of the JCI editorial board and editorial
      staff, I wish Gordon Tomaselli all the best in his new position as the dean of
      the Albert Einstein College of Medicine.

PMID- 30108191
TI  - The role of non-resolving inflammation in atherosclerosis.
AB  - Non-resolving inflammation drives the development of clinically dangerous
      atherosclerotic lesions by promoting sustained plaque inflammation, large
      necrotic cores, thin fibrous caps, and thrombosis. Resolution of inflammation is
      not merely a passive return to homeostasis, but rather an active process mediated
      by specific molecules, including fatty acid-derived specialized pro-resolving
      mediators (SPMs). In advanced atherosclerosis, there is an imbalance between
      levels of SPMs and proinflammatory lipid mediators, which results in sustained
      leukocyte influx into lesions, inflammatory macrophage polarization, and impaired
      efferocytosis. In animal models of advanced atherosclerosis, restoration of SPMs
      limits plaque progression by suppressing inflammation, enhancing efferocytosis,
      and promoting an increase in collagen cap thickness. This Review discusses the
      roles of non-resolving inflammation in atherosclerosis and highlights the unique
      therapeutic potential of SPMs in blocking the progression of clinically dangerous
      plaques.

PMID- 30108194
TI  - A conversation with Cornelia Bargmann.

PMID- 30108193
TI  - Role of sphingolipids in senescence: implication in aging and age-related
      diseases.
AB  - Aging is defined as the progressive deterioration of physiological function with
      age. Incidence of many pathologies increases with age, including neurological and
      cardiovascular diseases and cancer. Aging tissues become less adaptable and
      renewable, and cells undergo senescence, a process by which they "irreversibly"
      stop dividing. Senescence has been shown to serve as a tumor suppression
      mechanism with clear desirable effects. However, senescence also has deleterious
      consequences, especially for cardiovascular, metabolic, and immune systems.
      Sphingolipids are a major class of lipids that regulate cell biology, owing to
      their structural and bioactive properties and diversity. Their involvement in the
      regulation of aging and senescence has been demonstrated and studied in multiple
      organisms and cell types, especially that of ceramide and sphingosine-1
      phosphate; ceramide induces cellular senescence and sphingosine-1-phosphate
      delays it. These discoveries could be very useful in the future to understand
      aging mechanisms and improve therapeutic interventions.

PMID- 30108197
TI  - The epithelial-to-mesenchymal transition activator ZEB1 initiates a prometastatic
      competing endogenous RNA network.

PMID- 30108196
TI  - Key roles for lipid mediators in the adaptive immune response.
AB  - Chronic inflammation is an underlying feature of many diseases, including chronic
      obstructive pulmonary disease, rheumatoid arthritis, asthma, and multiple
      sclerosis. There is an increasing appreciation of the dysregulation of adaptive
      immunity in chronic inflammatory and allergic diseases. The discovery of
      specialized pro-resolving lipid mediators (SPMs) that actively promote the
      resolution of inflammation has opened new avenues for the treatment of chronic
      inflammatory diseases. Much work has been done focusing on the impact of SPMs on
      innate immune cells. However, much less is known about the influence of SPMs on
      the development of antigen-specific adaptive immune responses. This Review
      highlights the important breakthroughs concerning the effects of SPMs on the key
      cell types involved in the development of adaptive immunity, namely dendritic
      cells, T cells, and B cells.

PMID- 30108195
TI  - Leukotriene biosynthetic enzymes as therapeutic targets.
AB  - Leukotrienes are powerful immune-regulating lipid mediators with established
      pathogenic roles in inflammatory allergic diseases of the respiratory tract - in
      particular, asthma and hay fever. More recent work indicates that these lipids
      also contribute to low-grade inflammation, a hallmark of cardiovascular,
      neurodegenerative, and metabolic diseases as well as cancer. Biosynthesis of
      leukotrienes involves oxidative metabolism of arachidonic acid and proceeds via a
      set of soluble and membrane enzymes that are primarily expressed by cells of
      myeloid origin. In activated immune cells, these enzymes assemble at the
      endoplasmic and perinuclear membrane, constituting a biosynthetic complex. This
      Review describes recent advances in our understanding of the components of the
      leukotriene-synthesizing enzyme machinery, emerging opportunities for
      pharmacological intervention, and the development of new medicines exploiting
      both antiinflammatory and pro-resolving mechanisms.

PMID- 30108198
TI  - Urgent Cesarean Delivery Following a Spontaneous Coronary Artery Dissection.
AB  - BACKGROUND Spontaneous coronary artery dissection is the most common etiology of
      pregnancy-associated myocardial infarction. It is characterized by high rates of
      maternal morbidity and mortality and may cause fetal complications and death as
      well. CASE REPORT A 44-year-old female (G2P1) suffered from pregnancy-related
      spontaneous coronary artery dissection with dissection of distal left anterior
      descending coronary artery. The patient was hemodynamically stable and did not
      required revascularization, but signs of fetal distress were detected and thus an
      urgent cesarean delivery was performed. This emergency procedure was undertaken
      in the catheterization laboratory (Cath-Lab) right after coronary angiography,
      thanks to a multidisciplinary team. Health conditions of the newborn were good.
      The patient instead suffered from a recurrence of spontaneous coronary artery
      dissection 6 days later, complicated by left ventricular apical thrombus and
      epistenocardial pericarditis. The dissection self-healed in 1 month. CONCLUSIONS
      Careful evaluation of pregnancy-related spontaneous coronary artery dissection is
      needed to assess and manage both maternal and fetal complications. Under specific
      circumstances, a cesarean delivery may be required and be even performed in the
      Cath-Lab after coronary catheterization.

PMID- 30108199
TI  - Deciphering Key Pharmacological Pathways of Qingdai Acting on Chronic Myeloid
      Leukemia Using a Network Pharmacology-Based Strategy.
AB  - Qingdai, a traditional Chinese medicine (TCM) used for the treatment of chronic
      myeloid leukemia (CML) with good efficacy, has been used in China for decades.
      However, due to the complexity of traditional Chinese medicinal compounds, the
      pharmacological mechanism of Qingdai needs further research. In this study, we
      investigated the pharmacological mechanisms of Qingdai in the treatment of CML
      using network pharmacology approaches. First, components in Qingdai that were
      selected by pharmacokinetic profiles and biological activity predicted putative
      targets based on a combination of 2D and 3D similarity measures with known
      ligands. Then, an interaction network of Qingdai putative targets and known
      therapeutic targets for the treatment of chronic myeloid leukemia was
      constructed. By calculating the 4 topological features (degree, betweenness,
      closeness, and coreness) of each node in the network, we identified the candidate
      Qingdai targets according to their network topological importance. The composite
      compounds of Qingdai and the corresponding candidate major targets were further
      validated by a molecular docking simulation. Seven components in Qingdai were
      selected and 32 candidate Qingdai targets were identified; these were more
      frequently involved in cytokine-cytokine receptor interaction, cell cycle, p53
      signaling pathway, MAPK signaling pathway, and immune system-related pathways,
      which all play important roles in the progression of CML. Finally, the molecular
      docking simulation showed that 23 pairs of chemical components and candidate
      Qingdai targets had effective binding. This network-based pharmacology study
      suggests that Qingdai acts through the regulation of candidate targets to
      interfere with CML and thus regulates the occurrence and development of CML.

PMID- 30108201
TI  - Seroprevalence of TBEV in bank voles from Poland-a long-term approach.
AB  - Rodents are known to play a significant role as reservoir hosts for TBEV. During
      three sequential expeditions at 4-year intervals to three ecologically similar
      study sites in NE Poland, we trapped bank voles (Myodes glareolus) and then
      tested their blood for the presence of specific antiviral antibodies to TBEV. The
      strongest effects on seroprevalence were the extrinsic factors, site of capture
      of voles and year of sampling. Seroprevalence increased markedly with increasing
      host age, and our analysis revealed significant interactions among these three
      factors. Seroprevalence did not differ between the sexes. Therefore, based on the
      seroprevalence results, the dynamics of TBEV infection differ significantly in
      time, between local sub-populations of bank voles and with increasing host age.
      To fully understand the circulation of the virus among these reservoir hosts and
      in the environment, long-term monitoring is required and should employ a multi
      site approach, such as the one adopted in the current study.

PMID- 30108202
TI  - SOX2 recruits KLF4 to regulate nasopharyngeal carcinoma proliferation via
      PI3K/AKT signaling.
AB  - ABSTACT: SOX2 is a transcription factor that contributes to transcription
      modification and cancer, but the mechanism by which SOX2 regulates nasopharyngeal
      carcinoma cell proliferation is not well understood. Here, we identify a SOX2
      signaling pathway that facilitates nasopharyngeal carcinoma, where it is
      upregulated. SOX2 expression was associated with nasopharyngeal carcinoma patient
      survival. SOX2 knockdown inhibited cell proliferation, colony formation, and
      tumorigenesis in an subcutaneous mouse xenograft model system. Six hundred and
      ninety-nine candidate SOX2 downstream dysregulated genes were identified in
      nasopharyngeal carcinoma cells through cDNA microarray analysis. SOX2 recruited
      the nuclear transcription factor KLF4 to bind to the PIK3CA promoter upregulate
      PIK3CA expression, acting to enhance PI3K/AKT signaling and tumorigenesis by
      upregulating PIK3CA expression. Besides, overexpressing activated AKT or PIK3CA
      rescued the growth inhibition of cells due to SOX2 knockdown. Together, our study
      suggest that SOX2 exhibits oncogenic properties and may be a reliable molecular
      biomarker in nasopharyngeal carcinoma. Targeting SOX2 might be a promising
      treatment strategy for nasopharyngeal carcinoma treatment.

PMID- 30108200
TI  - PSD95 and nNOS interaction as a novel molecular target to modulate conditioned
      fear: relevance to PTSD.
AB  - Stimulation of N-methyl-D-aspartic acid receptors (NMDARs) and the resulting
      increase of nitric oxide (NO) production are critical for fear memory formation.
      Following NMDAR activation, efficient production of NO requires linking the 95
      kDa postsynaptic density protein (PSD95), a scaffolding protein to neuronal
      nitric oxide synthase (nNOS). A variety of previously studied NMDAR antagonists
      and NOS inhibitors can disrupt fear conditioning, but they also affect many other
      CNS functions such as motor activity, anxiety, and learning. We hypothesized that
      disrupting nNOS and PSD95 interaction in the amygdala, a critical site for fear
      memory formation, will reduce conditioned fear. Our results show that systemic
      treatment with ZL006, a compound that disrupts PSD95/nNOS binding, attenuates
      fear memory compared to its inactive isomer ZL007. Co-immunoprecipitation after
      fear conditioning showed a robust increase in the amygdala PSD95/nNOS binding,
      which was blocked by systemic pre-administration of ZL006. Treatment of amygdala
      slices with ZL006 also impaired long-term potentiation (LTP), a cellular
      signature of synaptic plasticity. Direct intra-amygdala infusion of ZL006 also
      attenuated conditioned fear. Finally, unlike NMDAR antagonist MK-801, ZL006 does
      not affect locomotion, social interaction, object recognition memory, and spatial
      memory. These findings support the hypothesis that disrupting the PSD95/nNOS
      interaction downstream of NMDARs selectively reduces fear memory, and highlights
      PSD95/nNOS interaction as a novel target for fear-related disorders, such as
      posttraumatic stress disorder.

PMID- 30108204
TI  - Long-Term Outcome of Splanchnic Vein Thrombosis in Cirrhosis.
AB  - INTRODUCTION: Little is known about the long-term outcome of cirrhotic patients
      with splanchnic vein thrombosis (SVT). This prospective cohort study aimed to
      describe the clinical presentation, bleeding incidence, thrombotic events, and
      mortality in patients with SVT associated with cirrhosis. METHODS: Among 604
      consecutive patients with SVT enrolled over 2 years, 149 had cirrhosis. Major
      bleeding, thrombotic events, and all-cause mortality were recorded during a 2
      year follow-up. In a subgroup, the degree of recanalization with or without
      anticoagulation therapy, and the correlation between clinical events and liver
      disease severity were also investigated. RESULTS: The most common thrombosis
      sites were the portal (88%) and mesenteric veins (34%). At presentation, 50% of
      patients were asymptomatic. Anticoagulation was administered to 92/149 patients
      for a median of 6.5 months. Vessel recanalization was documented in 47/98
      patients with a radiological follow-up. Anticoagulation was associated with a
      3.33-fold higher of recanalization rate, and a lower recurrent thrombosis rate,
      while patients with and without anticoagulation experienced a similar rate of
      major bleeding episodes. Mortality rates were 6.8 per 100 patient-years for
      patients with thrombosis completely or partially resolving during the follow-up,
      and 15.4 per 100 patient-years for those with stable or progressing thrombosis.
      An impact of SVT on survival was only apparent in patients with more advanced
      liver disease (Child-Pugh B-C). CONCLUSIONS: Patients with SVT and cirrhosis have
      a substantial long-term risk of recurrent thrombotic events, which is reduced by
      anticoagulation therapy without any increase in bleeding risk. Anticoagulation
      can improve the likelihood of vessel recanalization, and is associated with a
      lower risk of death for decompensated patients.

PMID- 30108203
TI  - Absent sleep EEG spindle activity in GluA1 (Gria1) knockout mice: relevance to
      neuropsychiatric disorders.
AB  - Sleep EEG spindles have been implicated in attention, sensory processing,
      synaptic plasticity and memory consolidation. In humans, deficits in sleep
      spindles have been reported in a wide range of neurological and psychiatric
      disorders, including schizophrenia. Genome-wide association studies have
      suggested a link between schizophrenia and genes associated with synaptic
      plasticity, including the Gria1 gene which codes for the GluA1 subunit of alpha
      amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor. Gria1-/- mice
      exhibit a phenotype relevant for neuropsychiatric disorders, including reduced
      synaptic plasticity and, at the behavioural level, attentional deficits leading
      to aberrant salience. In this study we report a striking reduction of EEG power
      density including the spindle-frequency range (10-15 Hz) during sleep in Gria1-/-
      mice. The reduction of spindle-activity in Gria1-/- mice was accompanied by
      longer REM sleep episodes, increased EEG slow-wave activity in the occipital
      derivation during baseline sleep, and a reduced rate of decline of EEG slow wave
      activity (0.5-4 Hz) during NREM sleep after sleep deprivation. These data provide
      a novel link between glutamatergic dysfunction and sleep abnormalities in a
      schizophrenia-relevant mouse model.

PMID- 30108205
TI  - Riluzole reduces amyloid beta pathology, improves memory, and restores gene
      expression changes in a transgenic mouse model of early-onset Alzheimer's
      disease.
AB  - Alzheimer's disease (AD) represents a major healthcare burden with no effective
      treatment. The glutamate modulator, riluzole, was shown to reverse many AD
      related gene expression changes and improve cognition in aged rats. However,
      riluzole's effect on amyloid beta (Abeta) pathology, a major histopathological
      hallmark of AD, remains unclear. 5XFAD transgenic mice, which harbor amyloid beta
      precursor protein (APP) and presenilin mutations and exhibit early Abeta
      accumulation, were treated with riluzole from 1 to 6 months of age. Riluzole
      significantly enhanced cognition and reduced Abeta42, Abeta40, Abeta oligomers
      levels, and Abeta plaque load in 5XFAD mice. RNA-Sequencing showed that riluzole
      reversed many gene expression changes observed in the hippocampus of 5XFAD mice,
      predominantly in expression of canonical gene markers for microglia, specifically
      disease-associated microglia (DAM), as well as neurons and astrocytes. Central to
      the cognitive improvements observed, riluzole reversed alterations in NMDA
      receptor subunits gene expression, which are essential for learning and memory.
      These data demonstrate that riluzole exerts a disease modifying effect in an
      Abeta mouse model of early-onset familial AD.

PMID- 30108206
TI  - A risk score model of 30-day readmission in ulcerative colitis after colectomy or
      proctectomy.
AB  - INTRODUCTION: The Center for Medicare and Medicaid Services established 30-day
      readmission rate as a key metric in measuring high-value, cost-conscious care;
      therefore, our aim is to develop a risk score for 30-day readmission in
      ulcerative colitis (UC) patients undergoing colectomy or proctectomy. METHODS:
      This study used data from the American College of Surgeons National Surgical
      Quality Improvement Program (ACS NSQIP) participant user file (2011-2015).
      Patients with UC undergoing colectomy or proctectomy were identified using ICD-9,
      10, and CPT codes. Stepwise multivariate analyses were used to determine risk
      factors associated with readmission including pre-operative conditions,
      laboratory results, operative variables, and post-operative complications. For
      readmission risk score assessment, a weighted logistic regression model was built
      and validated using ACS NSQIP 2011-2014 and 2015 data, respectively. RESULTS: A
      total of 4797 patients were included with 963 (20%) patients readmitted within 30
      days. Potentially modifiable risk factors included deep vein thrombosis,
      pulmonary embolism, renal insufficiency, wound infection, urinary tract
      infection, sepsis/septic shock, and pre-existing congestive heart failure. Ten
      percent of patients with a risk score between 0 and 9 were readmitted, 18.5% with
      a score between 10 and 19, 52.2% with a score between 20 and 29, and 59.6% in
      patients with a risk score >29. CONCLUSIONS: Multiple potentially preventable
      risk factors are associated with 30-day readmission following colectomy or
      proctectomy in UC patients. Higher risk scores are associated with increased risk
      of unplanned readmission.

PMID- 30108207
TI  - Chromosomal instability-induced senescence potentiates cell non-autonomous
      tumourigenic effects.
AB  - Chromosomal instability (CIN), a high rate of chromosome loss or gain, is often
      associated with poor prognosis and drug resistance in cancers. Aneuploid,
      including near-polyploid, cells contain an abnormal number of chromosomes and
      exhibit CIN. The post-mitotic cell fates following generation of different
      degrees of chromosome mis-segregation and aneuploidy are unclear. Here we used
      aneuploidy inducers, nocodazole and reversine, to create different levels of
      aneuploidy. A higher extent of aneuploid and near-polyploid cells in a given
      population led to senescence. This was in contrast to cells with relatively lower
      levels of abnormal ploidy that continued to proliferate. Our findings revealed
      that senescence was accompanied by DNA damage and robust p53 activation. These
      senescent cells acquired the senescence-associated secretory phenotype (SASP).
      Depletion of p53 reduced the number of senescent cells with concomitant increase
      in cells undergoing DNA replication. Characterisation of these SASP factors
      demonstrated that they conferred paracrine pro-tumourigenic effects such as
      invasion, migration and angiogenesis both in vitro and in vivo. Finally, a
      correlation between increased aneuploidy and senescence was observed at the
      invasive front in breast carcinomas. Our findings demonstrate functional non
      equivalence of discernable aneuploidies on tumourigenesis and suggest a cell non
      autonomous mechanism by which aneuploidy-induced senescent cells and SASP can
      affect the tumour microenvironment to promote tumour progression.

PMID- 30108208
TI  - Association study and mutation sequencing of genes on chromosome 15q11-q13
      identified GABRG3 as a susceptibility gene for autism in Chinese Han population.
AB  - Cytogenetic studies suggested that chromosome 15q11-q13 might be a candidate
      region that increases the risk of autism. Previous association studies in
      Caucasian populations identified the risk variants of genes in this region.
      However, the association of these genes with autism in Chinese Han population
      remains unclear. Herein, 512 autism trios were utilized for a family-based
      association study of 41 tag single nucleotide polymorphisms (SNPs) in this region
      to explore the association between protein-coding genes on chromosome 15q11-q13
      and autism in Chinese Han population. Furthermore, we sequenced these autism
      related genes to detect rare variants in 512 autism trios and 575 healthy
      controls. Our results showed that the C allele of rs7180500 in GABRG3 was a risk
      variant for autism (p = 0.00057). The expression quantitative trait loci (eQTL)
      analysis revealed that the C allele of rs7180500 might be associated with the
      expression of GABRG3 in the cerebellum (Braineac: p = 0.0048; GTEx: p = 0.0010).
      Moreover, the sequencing identified two rare variants rs201602655 (p.Val233Met)
      and rs201427468 (p.Pro365Ser) in GABRG3 and six rare variants in GABRB3 in
      autistic patients. Among these variants, rs201602655 (p.Val233Met) in GABRG3 were
      observed in 9 of 512 autistic children and 2 of 575 healthy controls (Pearson
      chi2-test, chi2 = 5.375, p = 0.020). The functional prediction indicated that
      rs201602655 (p.Val233Met) might be deleterious. Thus, these findings demonstrated
      that GABRG3 might contribute to the pathogenesis of autism in Chinese Han
      population.

PMID- 30108210
TI  - Non-linear response of summertime marine productivity to increased meltwater
      discharge around Greenland.
AB  - Runoff from the Greenland Ice Sheet (GrIS) is thought to enhance marine
      productivity by adding bioessential iron and silicic acid to coastal waters.
      However, experimental data suggest nitrate is the main summertime growth-limiting
      resource in regions affected by meltwater around Greenland. While meltwater
      contains low nitrate concentrations, subglacial discharge plumes from marine
      terminating glaciers entrain large quantities of nitrate from deep seawater.
      Here, we characterize the nitrate fluxes that arise from entrainment of seawater
      within these plumes using a subglacial discharge plume model. The upwelled flux
      from 12 marine-terminating glaciers is estimated to be >1000% of the total
      nitrate flux from GrIS discharge. This plume upwelling effect is highly sensitive
      to the glacier grounding line depth. For a majority of Greenland's marine
      terminating glaciers nitrate fluxes will diminish as they retreat. This decline
      occurs even if discharge volume increases, resulting in a negative impact on
      nitrate availability and thus summertime marine productivity.

PMID- 30108209
TI  - Fast and powerful genome wide association of dense genetic data with high
      dimensional imaging phenotypes.
AB  - Genome wide association (GWA) analysis of brain imaging phenotypes can advance
      our understanding of the genetic basis of normal and disorder-related variation
      in the brain. GWA approaches typically use linear mixed effect models to account
      for non-independence amongst subjects due to factors, such as family relatedness
      and population structure. The use of these models with high-dimensional imaging
      phenotypes presents enormous challenges in terms of computational intensity and
      the need to account multiple testing in both the imaging and genetic domain. Here
      we present a method that makes mixed models practical with high-dimensional
      traits by a combination of a transformation applied to the data and model, and
      the use of a non-iterative variance component estimator. With such speed
      enhancements permutation tests are feasible, which allows inference on powerful
      spatial tests like the cluster size statistic.

PMID- 30108211
TI  - Revealing circadian mechanisms of integration and resilience by visualizing clock
      proteins working in real time.
AB  - The circadian clock proteins KaiA, KaiB, and KaiC reconstitute a remarkable circa
      24 h oscillation of KaiC phosphorylation that persists for many days in vitro.
      Here we use high-speed atomic force microscopy (HS-AFM) to visualize in real time
      and quantify the dynamic interactions of KaiA with KaiC on sub-second timescales.
      KaiA transiently interacts with KaiC, thereby stimulating KaiC autokinase
      activity. As KaiC becomes progressively more phosphorylated, KaiA's affinity for
      KaiC weakens, revealing a feedback of KaiC phosphostatus back onto the KaiA
      binding events. These non-equilibrium interactions integrate high-frequency
      binding and unbinding events, thereby refining the period of the longer term
      oscillations. Moreover, this differential affinity phenomenon broadens the range
      of Kai protein stoichiometries that allow rhythmicity, explaining how the
      oscillation is resilient in an in vivo milieu that includes noise. Therefore,
      robustness of rhythmicity on a 24-h scale is explainable by molecular events
      occurring on a scale of sub-seconds.

PMID- 30108212
TI  - Spin and orbital structure of the first six holes in a silicon metal-oxide
      semiconductor quantum dot.
AB  - Valence band holes confined in silicon quantum dots are attracting significant
      attention for use as spin qubits. However, experimental studies of single-hole
      spins have been hindered by challenges in fabrication and stability of devices
      capable of confining a single hole. To fully utilize hole spins as qubits, it is
      crucial to have a detailed understanding of the spin and orbital states. Here we
      show a planar silicon metal-oxide-semiconductor-based quantum dot device and
      demonstrate operation down to the last hole. Magneto-spectroscopy studies show
      magic number shell filling consistent with the Fock-Darwin states of a circular
      two-dimensional quantum dot, with the spin filling sequence of the first six
      holes consistent with Hund's rule. Next, we use pulse-bias spectroscopy to
      determine that the orbital spectrum is heavily influenced by the strong hole-hole
      interactions. These results provide a path towards scalable silicon hole-spin
      qubits.

PMID- 30108213
TI  - A novel probabilistic forecast system predicting anomalously warm 2018-2022
      reinforcing the long-term global warming trend.
AB  - In a changing climate, there is an ever-increasing societal demand for accurate
      and reliable interannual predictions. Accurate and reliable interannual
      predictions of global temperatures are key for determining the regional climate
      change impacts that scale with global temperature, such as precipitation
      extremes, severe droughts, or intense hurricane activity, for instance. However,
      the chaotic nature of the climate system limits prediction accuracy on such
      timescales. Here we develop a novel method to predict global-mean surface air
      temperature and sea surface temperature, based on transfer operators, which
      allows, by-design, probabilistic forecasts. The prediction accuracy is equivalent
      to operational forecasts and its reliability is high. The post-1998 global
      warming hiatus is well predicted. For 2018-2022, the probabilistic forecast
      indicates a warmer than normal period, with respect to the forced trend. This
      will temporarily reinforce the long-term global warming trend. The coming warm
      period is associated with an increased likelihood of intense to extreme
      temperatures. The important numerical efficiency of the method (a few hundredths
      of a second on a laptop) opens the possibility for real-time probabilistic
      predictions carried out on personal mobile devices.

PMID- 30108214
TI  - Chromatin regulates IL-33 release and extracellular cytokine activity.
AB  - IL-33 is an epithelium-derived, pro-inflammatory alarmin with enigmatic nuclear
      localization and chromatin binding. Here we report the functional properties of
      nuclear IL-33. Overexpression of IL-33 does not alter global gene expression in
      transduced epithelial cells. Fluorescence recovery after photobleaching data show
      that the intranuclear mobility of IL-33 is ~10-fold slower than IL-1alpha,
      whereas truncated IL-33 lacking chromatin-binding activity is more mobile. WT IL
      33 is more resistant to necrosis-induced release than truncated IL-33 and has a
      relatively slow, linear release over time after membrane dissolution as compared
      to truncated IL-33 or IL-1alpha. Lastly, IL-33 and histones are released as a
      high-molecular weight complex and synergistically activate receptor-mediated
      signaling. We thus propose that chromatin binding is a post-translational
      mechanism that regulates the releasability and ST2-mediated bioactivity of IL-33
      and provide a paradigm to further understand the enigmatic functions of nuclear
      cytokines.

PMID- 30108216
TI  - A possible candidate for triply degenerate point fermions in trigonal layered
      PtBi2.
AB  - Triply degenerate point (TP) fermions in tungsten-carbide-type materials (e.g.,
      MoP), which represent new topological states of quantum matter, have generated
      immense interest recently. However, the TPs in these materials are found to be
      far below the Fermi level, leading to the TP fermions having less contribution to
      low-energy quasiparticle excitations. Here, we theoretically predict the
      existence of TP fermions with TP points close to the Fermi level in trigonal
      layered PtBi2 by ab initio calculations, and experimentally verify the predicted
      band topology by magnetotransport measurements under high magnetic fields up to
      40 T. Analyses of both the pronounced Shubnikov-de Haas and de Haas-van Alphen
      oscillations reveal the existence of six principal Fermi pockets. Our
      experimental results, together with those from ab initio calculations, reveal the
      interplay between transport behaviors and unique electronic structures, and
      support the existence of TP fermions in trigonal layered PtBi2.

PMID- 30108215
TI  - The tyrosine phosphatase SHP2 controls TGFbeta-induced STAT3 signaling to
      regulate fibroblast activation and fibrosis.
AB  - Uncontrolled activation of TGFbeta signaling is a common denominator of fibrotic
      tissue remodeling. Here we characterize the tyrosine phosphatase SHP2 as a
      molecular checkpoint for TGFbeta-induced JAK2/STAT3 signaling and as a potential
      target for the treatment of fibrosis. TGFbeta stimulates the phosphatase activity
      of SHP2, although this effect is in part counterbalanced by inhibitory effects on
      SHP2 expression. Stimulation with TGFbeta promotes recruitment of SHP2 to JAK2 in
      fibroblasts with subsequent dephosphorylation of JAK2 at Y570 and activation of
      STAT3. The effects of SHP2 on STAT3 activation translate into major regulatory
      effects of SHP2 on fibroblast activation and tissue fibrosis. Genetic or
      pharmacologic inactivation of SHP2 promotes accumulation of JAK2 phosphorylated
      at Y570, reduces JAK2/STAT3 signaling, inhibits TGFbeta-induced fibroblast
      activation and ameliorates dermal and pulmonary fibrosis. Given the availability
      of potent SHP2 inhibitors, SHP2 might thus be a potential target for the
      treatment of fibrosis.

PMID- 30108217
TI  - Gating mechanism of the extracellular entry to the lipid pathway in a TMEM16
      scramblase.
AB  - Members of the TMEM16/ANO family of membrane proteins are Ca2+-activated
      phospholipid scramblases and/or Cl- channels. A membrane-exposed hydrophilic
      groove in these proteins serves as a shared translocation pathway for ions and
      lipids. However, the mechanism by which lipids gain access to and permeate
      through the groove remains poorly understood. Here, we combine quantitative
      scrambling assays and molecular dynamic simulations to identify the key steps
      regulating lipid movement through the groove. Lipid scrambling is limited by two
      constrictions defined by evolutionarily conserved charged and polar residues, one
      extracellular and the other near the membrane mid-point. The region between these
      constrictions is inaccessible to lipids and water molecules, suggesting that the
      groove is in a non-conductive conformation. A sequence of lipid-triggered
      reorganizations of interactions between these residues and the permeating lipids
      propagates from the extracellular entryway to the central constriction, allowing
      the groove to open and coordinate the headgroups of transiting lipids.

PMID- 30108219
TI  - A tutorial on how not to over-interpret STRUCTURE and ADMIXTURE bar plots.
AB  - Genetic clustering algorithms, implemented in programs such as STRUCTURE and
      ADMIXTURE, have been used extensively in the characterisation of individuals and
      populations based on genetic data. A successful example is the reconstruction of
      the genetic history of African Americans as a product of recent admixture between
      highly differentiated populations. Histories can also be reconstructed using the
      same procedure for groups that do not have admixture in their recent history,
      where recent genetic drift is strong or that deviate in other ways from the
      underlying inference model. Unfortunately, such histories can be misleading. We
      have implemented an approach, badMIXTURE, to assess the goodness of fit of the
      model using the ancestry "palettes" estimated by CHROMOPAINTER and apply it to
      both simulated data and real case studies. Combining these complementary analyses
      with additional methods that are designed to test specific hypotheses allows a
      richer and more robust analysis of recent demographic history.

PMID- 30108220
TI  - Publisher Correction: Achieving high permeability and enhanced selectivity for
      Angstrom-scale separations using artificial water channel membranes.
AB  - The original version of this Article contained an error in the spelling of the
      author Woochul Song, which was incorrectly given as Woochul C. Song. This has
      been corrected in both the PDF and HTML versions of the Article.

PMID- 30108218
TI  - Sleep loss causes social withdrawal and loneliness.
AB  - Loneliness and social isolation markedly increase mortality risk, and are linked
      to numerous mental and physical comorbidities, including sleep disruption. But
      does sleep loss causally trigger loneliness? Here, we demonstrate that a lack of
      sleep leads to a neural and behavioral phenotype of social withdrawal and
      loneliness; one that can be perceived by other members of society, and
      reciprocally, makes those societal members lonelier in return. We propose a model
      in which sleep loss instigates a propagating, self-reinforcing cycle of social
      separation and withdrawal.

PMID- 30108221
TI  - Engineering the spin couplings in atomically crafted spin chains on an elemental
      superconductor.
AB  - Magnetic atoms on a superconductor give rise to Yu-Shiba-Rusinov (YSR) states
      within the superconducting energy gap. A spin chain of magnetic adatoms on an s
      wave superconductor may lead to topological superconductivity accompanied by the
      emergence of Majorana modes at the chain ends. For their usage in quantum
      computation, it is a prerequisite to artificially assemble the chains and control
      the exchange couplings between the spins in the chain and in the substrate. Here,
      using a scanning tunneling microscope tip, we demonstrate engineering of the
      energy levels of the YSR states by placing interstitial Fe atoms in close
      proximity to adsorbed Fe atoms on an oxidized Ta surface. Based on this prototype
      platform, we show that the interaction within a long chain can be strengthened by
      linking the adsorbed Fe atoms with the interstitial ones. Our work adds an
      important step towards the controlled design and manipulation of Majorana end
      states.

PMID- 30108222
TI  - Charge carrier-selective contacts for nanowire solar cells.
AB  - Charge carrier-selective contacts transform a light-absorbing semiconductor into
      a photovoltaic device. Current record efficiency solar cells nearly all use
      advanced heterojunction contacts that simultaneously provide carrier selectivity
      and contact passivation. One remaining challenge with heterojunction contacts is
      the tradeoff between better carrier selectivity/contact passivation (thicker
      layers) and better carrier extraction (thinner layers). Here we demonstrate that
      the nanowire geometry can remove this tradeoff by utilizing a permanent local
      gate (molybdenum oxide surface layer) to control the carrier selectivity of an
      adjacent ohmic metal contact. We show an open-circuit voltage increase for single
      indium phosphide nanowire solar cells by up to 335 mV, ultimately reaching 835
      mV, and a reduction in open-circuit voltage spread from 303 to 105 mV after
      application of the surface gate. Importantly, reference experiments show that the
      carriers are not extracted via the molybdenum oxide but the ohmic metal contacts
      at the wire ends.

PMID- 30108223
TI  - Spatially similar surface energy flux perturbations due to greenhouse gases and
      aerosols.
AB  - Despite distinct geographic distributions of top-of-the-atmosphere radiative
      forcing, anthropogenic greenhouse gases and aerosols have been found to produce
      similar patterns of climate response in atmosphere-and-ocean coupled climate
      model simulations. Understanding surface energy flux changes, a crucial pathway
      by which atmospheric forcing is communicated to the ocean, is a vital bridge to
      explaining the similar full atmosphere-and-ocean responses to these disparate
      forcings. Here we analyze the fast, atmosphere-driven change in surface energy
      flux caused by present-day greenhouse gases vs aerosols to elucidate its role in
      shaping the subsequent slow, coupled response. We find that the surface energy
      flux response patterns achieve roughly two-thirds of the anti-correlation seen in
      the fully coupled response, driven by Rossby waves excited by symmetric changes
      to the land-sea contrast. Our results suggest that atmosphere and land surface
      processes are capable of achieving substantial within-hemisphere homogenization
      in the climate response to disparate forcers on fast, societally-relevant
      timescales.

PMID- 30108224
TI  - Exercise-induced bronchoconstriction: prevalence, pathophysiology, patient
      impact, diagnosis and management.
AB  - Exercise-induced bronchoconstriction (EIB) can occur in individuals with and
      without asthma, and is prevalent among athletes of all levels. In patients with
      asthma, symptoms of EIB significantly increase the proportion reporting feelings
      of fearfulness, frustration, isolation, depression and embarrassment compared
      with those without symptoms. EIB can also prevent patients with asthma from
      participating in exercise and negatively impact their quality of life. Diagnosis
      of EIB is based on symptoms and spirometry or bronchial provocation tests; owing
      to low awareness of EIB and lack of simple, standardised diagnostic methods,
      under-diagnosis and mis-diagnosis of EIB are common. To improve the rates of
      diagnosis of EIB in primary care, validated and widely accepted symptom-based
      questionnaires are needed that can accurately replicate the current diagnostic
      standards (forced expiratory volume in 1 s reductions observed following exercise
      or bronchoprovocation challenge) in patients with and without asthma. In patients
      without asthma, EIB can be managed by various non-pharmacological methods and the
      use of pre-exercise short-acting beta2-agonists (SABAs). In patients with asthma,
      EIB is often associated with poor asthma control but can also occur in
      individuals who have good control when not exercising. Inhaled corticosteroids
      are recommended when asthma control is suboptimal; however, pre-exercise SABAs
      are also widely used and are recommended as the first-line therapy. This review
      describes the burden, key features, diagnosis and current treatment approaches
      for EIB in patients with and without asthma and serves as a call to action for
      family physicians to be aware of EIB and consider it as a potential diagnosis.

PMID- 30108226
TI  - Confined small-sized cobalt catalysts stimulate carbon-chain growth reversely by
      modifying ASF law of Fischer-Tropsch synthesis.
AB  - Fischer-Tropsch synthesis (FTS) is a promising technology to convert syngas
      derived from non-petroleum-based resources to valuable chemicals or fuels.
      Selectively producing target products will bring great economic benefits, but
      unfortunately it is theoretically limited by Anderson-Schulz-Flory (ASF) law.
      Herein, we synthesize size-uniformed cobalt nanocrystals embedded into mesoporous
      SiO2 supports, which is likely the structure of water-melon seeds inside pulps.
      We successfully tune the selectivity of products from diesel-range hydrocarbons
      (66.2%) to gasoline-range hydrocarbons (62.4%) by controlling the crystallite
      sizes of confined cobalt from 7.2 to 11.4 nm, and modify the ASF law. Generally,
      larger Co crystallites increase carbon-chain growth, producing heavier
      hydrocarbons. But here, we interestingly observe a reverse phenomenon: the
      uniformly small-sized cobalt crystallites can strongly adsorb active C* species,
      and the confined structure will inhibit aggregation of cobalt crystallites and
      escape of reaction intermediates in FTS, inducing the higher selectivity towards
      heavier hydrocarbons.

PMID- 30108225
TI  - Two-dimensional type-II Dirac fermions in layered oxides.
AB  - Relativistic massless Dirac fermions can be probed with high-energy physics
      experiments, but appear also as low-energy quasi-particle excitations in
      electronic band structures. In condensed matter systems, their massless nature
      can be protected by crystal symmetries. Classification of such symmetry-protected
      relativistic band degeneracies has been fruitful, although many of the predicted
      quasi-particles still await their experimental discovery. Here we reveal, using
      angle-resolved photoemission spectroscopy, the existence of two-dimensional type
      II Dirac fermions in the high-temperature superconductor La1.77Sr0.23CuO4. The
      Dirac point, constituting the crossing of [Formula: see text] and [Formula: see
      text] bands, is found approximately one electronvolt below the Fermi level (EF)
      and is protected by mirror symmetry. If spin-orbit coupling is considered, the
      Dirac point degeneracy is lifted and the bands acquire a topologically non
      trivial character. In certain nickelate systems, band structure calculations
      suggest that the same type-II Dirac fermions can be realised near EF.

PMID- 30108227
TI  - A cancer vaccine approach for personalized treatment of Lynch Syndrome.
AB  - Lynch syndrome (LS) is a cancer predisposition disorder wherein patients have a
      70-80% lifetime risk of developing colorectal cancers (CRC). Finding germline
      mutations in predisposing genes allows for risk assessment of CRC development.
      Here we report a germline heterozygous frame-shift mutation in the mismatch
      repair MLH1 gene which was identified in members of two unrelated LS families.
      Since defects in DNA mismatch repair genes generate frame-shift mutations giving
      rise to highly immunogenic neoepitopes, we postulated that vaccination with these
      mutant peptide antigens could offer promising treatment options to LS patients.
      To this end we performed whole-exome and RNA seq analysis on the blood and tumour
      samples from an LS-CRC patient, and used our proprietary neoepitope
      prioritization pipeline OncoPeptVAC to select peptides, and confirm their
      immunogenicity in an ex vivo CD8+ T cell activation assay. Three neoepitopes
      derived from the tumour of this patient elicited a potent CD8+ T cell response.
      Furthermore, analysis of the tumour-associated immune infiltrate revealed CD8+ T
      cells expressing low levels of activation markers, suggesting mechanisms of
      immune suppression at play in this relapsed tumour. Taken together, our study
      paves the way towards development of a cancer vaccine to treat or delay the
      onset/relapse of LS-CRC.

PMID- 30108228
TI  - Mid-and long-term efficacy of endovascular-based procedures for Cockett syndrome.
AB  - To investigate the mid- and long-term results of endovascular-based procedures
      for Cockett syndrome. The clinical data of 412 patients with Cockett syndrome
      treated between January 2003 and September 2017 were retrospectively analyzed. In
      these patients, 231 cases were acute left iliac femoral vein thrombosis (group
      A), and 181 cases were chronic venous insufficiency (group B), and different
      endovascular procedures and/or hybrid procedures were performed. In group A, the
      technique success rate was 100% (231/231); the left iliac vein in 5 patients
      showed no stenosis or occlusion, and the incidence of pathological changes in the
      left iliac vein was 97.8% (226/231); a total of 182 stents were implanted. In
      group B, the technique success rate was 99.4% (180/181); the average pressure
      difference between the proximal and distal portion of the pathological left iliac
      veins decreased from preoperative (18 +/- 4.45) cmH2O to postoperative (4 +/-
      3.02) cmH2O (P < 0.01); 89 patients, complicated with valvular incompetence in
      the left superficial femoral vein, underwent a second-stage femoral valve repair.
      Follow-up ranged from 3 months to 8 years, with an average of 35.6 months, and
      intrastent thrombosis occurred in 15 cases of group A and in 2 cases of group B.
      Endovascular-based procedures offer favorable mid- and long-term results in
      treatment of Cockett syndrome, which in combination with Fogarty catheter
      thrombectomy or catheter-directed thrombolysis is a beneficial complementary
      treatment for patients with acute iliac femoral vein thrombosis.

PMID- 30108229
TI  - Studies on structure property relations of efficient decal substrates for
      industrial grade membrane electrode assembly development in pemfc.
AB  - Electrode fabrication and membrane electrode assembly (MEA) processes are
      critical steps in polymer electrolyte membrane fuel cell (PEMFC) technology. The
      properties of decal substrate material are important in decal coating technique
      for efficient transfer of catalyst layer. In the present study, MEAs are
      fabricated in decal method using 6 different decal substrates among which
      polypropylene (PP) is found ideal. Morphological, thermal, spectroscopic and
      sessile drop measurements are conducted for 6 decal substrates to evaluate the
      thermal and physicochemical properties. Studies indicate PP is thermally stable
      at hot-press conditions, having optimal hydrophobicity that hinders the
      coagulation of catalyst ink slurry cast. The pristine PP film has been identified
      to showcase 100% transfer yield onto the Nafion membrane without contamination
      and delamination of catalyst layer from membrane. The PP based MEAs are evaluated
      underconstant current mode in a hydrogen-oxygen fuel cell test fixture. The
      performance is found to be of 0.6 V at a constant current density of 1.2 A.cm-2.
      Besides, the cost of PP-film is only 7.5% of Kapton-film, and hence the current
      research work enables the high throughput electrode fabrication process for PEMFC
      commercialization.

PMID- 30108231
TI  - Seasonal variability of diet and trophic level of the gelatinous predator Pelagia
      noctiluca (Scyphozoa).
AB  - Jellyfish populations apparently have increased in some places around the world
      and human problems with them also have increased. However, effects of jellyfish
      outbreaks in the ecosystems remain poorly understood and little or no information
      is available on their dietary preferences - in relation to the seasonal shifts of
      prey abundance - and on the potential variability of their impact on marine food
      webs. The mauve stinger Pelagia noctiluca (Forsskal, 1775) is by far the most
      common outbreak-forming scyphozoan jellyfish in the Western Mediterranean. By use
      of a combination of stomach contents, stable isotope (SI) and fatty acid (FA)
      analyses, we tested the hypothesis that changes in the seasonal dietary sources
      of P. noctiluca parallel changes in the FA and SI composition. Stomach content
      and biomarker analyses suggested that P. noctiluca is not a selective predator,
      cyclically shifting between carnivory and omnivory depending on the seasonality
      of accessible prey. The combination of SI and FA analyses highlighted the
      importance of microzooplankton as prey. Specific FA biomarkers showed that the
      diet of P. noctiluca changed seasonally depending on the availability of living
      plankton or suspended detritus. This study also revealed significant biochemical
      differences between jellyfish somatic and gonadal tissues, with total fatty acid
      concentration in the gonads up to ten times higher than in the somatic tissues.

PMID- 30108230
TI  - Tmc2 expression partially restores auditory function in a mouse model of
      DFNB7/B11 deafness caused by loss of Tmc1 function.
AB  - Mouse Tmc1 and Tmc2 are required for sensory transduction in cochlear and
      vestibular hair cells. Homozygous Tmc1?/? mice are deaf, Tmc2?/? mice have normal
      hearing, and double homozygous Tmc1?/?; Tmc2?/? mice have deafness and profound
      vestibular dysfunction. These phenotypes are consistent with their different
      spatiotemporal expression patterns. Tmc1 expression is persistent in cochlear and
      vestibular hair cells, whereas Tmc2 expression is transient in cochlear hair
      cells but persistent in vestibular hair cells. On the basis of these findings, we
      hypothesized that persistent Tmc2 expression in mature cochlear hair cells could
      restore auditory function in Tmc1?/? mice. To express Tmc2 in mature cochlear
      hair cells, we generated a transgenic mouse line, Tg[PTmc1::Tmc2], in which Tmc2
      cDNA is expressed under the control of the Tmc1 promoter. The Tg[PTmc1::Tmc2]
      transgene slightly but significantly restored hearing in young Tmc1?/? mice,
      though hearing thresholds were elevated with age. The elevation of hearing
      thresholds was associated with deterioration of sensory transduction in inner
      hair cells and loss of outer hair cell function. Although sensory transduction
      was retained in outer hair cells, their stereocilia eventually degenerated. These
      results indicate distinct roles and requirements for Tmc1 and Tmc2 in mature
      cochlear hair cells.

PMID- 30108232
TI  - Facilitating CAD/CAM nasoalveolar molding therapy with a novel click-in system
      for nasal stents ensuring a quick and user-friendly chairside nasal stent
      exchange.
AB  - Nasoalveolar molding (NAM) aims to improve nasal symmetry with a nasal stent in
      cleft lip and palate (CLP) patients. When plates have to be exchanged because of
      dentoalveolar growth or cleft reduction, the nasal stent has to be mounted onto a
      new plate. This procedure elongates visiting hours for patients and parents or
      requires second treatment sessions. This study introduces a quick-lock additive
      manufacturing solution for chairside nasal stent exchange called RapidNAM. A
      novel taping retention pin has been designed that enables nasal stent insertion.
      Patients with unilateral CLP were included in this study. Plaster models were
      digitalized and measured by two independent observers. Two methods of CAD/CAM
      molding therapies were compared: (i) conventional adhesion of a nasal stent
      (CAD/CAM NAM); (ii) quick-lock system in which the nasal stent was transferred to
      another plate (RapidNAM). CAD/CAM NAM and its refinement RapidNAM significantly
      increased the cleft-side nasal height and tilted the nose towards symmetry. The
      quick-lock system minimizes wire adaptations, since the pre-existing stent can be
      reused. The new nasal stent development seems a feasible solution to minimize
      visiting hours but with clinically satisfactory results. This new nasal stent
      system combines traditional elements of NAM with CAD/CAM-technology.

PMID- 30108233
TI  - Laplace-domain diffuse optical measurement.
AB  - Time-domain diffuse optical measurement systems determine depth-resolved
      absorption changes by using the time of flight distribution of the detected
      photons. It is well known that certain feature data, such as the Laplace
      transform of the temporal point spread function, is sufficient for image
      reconstruction and diffuse optical sensing. Conventional time-domain systems
      require the acquisition of full temporal profiles of diffusive photons and then
      numerically compute the feature dataset, for example, Laplace transformed
      intensities for imaging applications. We have proposed a novel method for
      directly obtaining the Laplace transform data. Our approach can significantly
      improve the data acquisition speed for time-domain diffuse optical imaging. We
      also demonstrated that the use of negative Laplace parameters can provide
      enhanced sensitivity to perturbations located in deep regions.

PMID- 30108234
TI  - Electrochemical metallization cell with solid phase tunable Ge2Sb2Te5
      electrolyte.
AB  - Electrochemical metallization (ECM) cell kinetics are strongly determined by the
      electrolyte and can hardly be altered after the cell has been fabricated. Solid
      state property tunable electrolytes in response to external stimuli are therefore
      desirable to introduce additional operational degree of freedom to the ECM cells,
      enabling novel applications such as multistate memory and reconfigurable
      computation. In this work, we use Ge2Sb2Te5(GST) as the electrolyte material
      whose solid state is switched from the amorphous(a) to the crystalline(c) phase
      thermally. Electrical heating too is readily achievable. The resistive switching
      characteristics of the cells with different GST phases are examined. The
      magnitude of the high resistance, the SET voltage and the on/off ratio are found
      to be considerably affected by the solid phase of GST, whereas the magnitude of
      the low resistance is least affected. Moreover, a transition from volatile to
      nonvolatile SET switching is only observed for c-GST based cell under prolonged
      voltage sweep, but not for a-GST based cell. This work provides a springboard for
      more studies on the manipulation of the ECM cell kinetics by tunable electrolyte
      and the resulting unprecedented device functionalities.

PMID- 30108236
TI  - An experimentally-achieved information-driven Brownian motor shows maximum power
      at the relaxation time.
AB  - We present an experimental realization of an information-driven Brownian motor by
      periodically cooling a Brownian particle trapped in a harmonic potential
      connected to a single heat bath, where cooling is carried out by the information
      process consisting of measurement and feedback control. We show that the random
      motion of the particle is rectified by symmetry-broken feedback cooling where the
      particle is cooled only when it resides on the specific side of the potential
      center at the instant of measurement. Studying how the motor thermodynamics
      depends on cycle period tau relative to the relaxation time tauB of the Brownian
      particle, we find that the ratcheting of thermal noise produces the maximum work
      extraction when tau >= 5tauB, while the extracted power is maximum near tau =
      tauB, implying the optimal operating time for the ratcheting process. In
      addition, we find that the average transport velocity is monotonically decreased
      as tau increases and present the upper bound for the velocity.

PMID- 30108235
TI  - Trends in pulmonary embolism in patients infected with HIV during the combination
      antiretroviral therapy era in Spain: A nationwide population-based study.
AB  - Chronic infections are a major factor in the development of pulmonary embolism
      (PE). We aimed to evaluate the trends of PE-related hospitalizations and PE
      related deaths in people living with HIV (PLWH) during the era of combination
      antiretroviral therapy (cART) through a retrospective study in Spain. Data were
      collected from the Minimum Basic Data Set (MBDS) between 1997 and 2013. The study
      period was fragmented into four calendar periods (1997-1999, 2000-2003, 2004
      2007, and 2008-2013). The rate of PE-related hospitalizations remained stable in
      PLWH (P = 0.361). HIV-monoinfected patients had a higher incidence than HIV/HCV
      coinfected patients during all follow-up [(98.7 (95%CI = 92.2; 105.1); P <
      0.001], but PE incidence decreased in HIV-monoinfected patients (P < 0.001) and
      increased in HIV/HCV-coinfected patients (P < 0.001). Concretely, the rate of PE
      related hospitalizations decreased significantly in patients monoinfected with
      HIV [from 203.6 (95%CI = 175.7; 231.6) events per 100,000 patient-years in 1997
      1999 to 74.3 (95%CI = 66.1; 82.3) in 2008-2013; P < 0.001], while patients
      coinfected with HIV/HCV had a significant increase [from 16.3 (95%CI = 11; 21.6)
      in 1997-1999 to 53.3 (95%CI = 45.9; 60.6) in 2008-2013; P < 0.001]. The mortality
      rate of PE-related hospitalizations showed a similar trend as PE incidence. In
      conclusion, the epidemiological trends of PE in PLWH changed during the cART era,
      with decreases in incidence and mortality in HIV-monoinfected and increases in
      both variables in patients coinfected with HIV/HCV.

PMID- 30108237
TI  - Sedimentary signals of recent faulting along an old strand of the San Andreas
      Fault, USA.
AB  - Continental transform fault systems are fundamental features in plate tectonics.
      These complex systems often constitute multiple fault strands with variable
      spatio-temporal histories. Here, we re-evaluate the complex history of the San
      Andreas Fault along a restraining bend in southern California (USA). The Mission
      Creek strand of the San Andreas Fault is a major geologic structure with ~90 km
      of strike-slip displacement but is currently mapped as inactive. Quaternary
      deposits record sediment dispersal across the fault from upland catchments and
      yield key markers of the fault's displacement history. Our sediment provenance
      analysis from the Deformed Gravels of Whitewater and the Cabezon Fanglomerate
      provide detrital geochronologic and lithologic signatures of potential sources
      within the San Bernardino Mountains and Little San Bernardino Mountains.
      Statistical analysis shows that the Cabezon Fanglomerate is most compatible with
      the Mission Creek and Morongo Valley Canyon sources, rather than the Whitewater
      Canyon as previously suggested. We propose that displacement since deposition
      ~500-100 ka across the Mission Creek strand has separated these deposits from
      their original sources. These findings challenge the current paradigm that the
      Mission Creek strand is inactive and suggest that the fault continues to be a
      primary structure in accommodating deformation along the Pacific-North American
      plate boundary.

PMID- 30108240
TI  - Lake sediment fecal and biomass burning biomarkers provide direct evidence for
      prehistoric human-lit fires in New Zealand.
AB  - Deforestation associated with the initial settlement of New Zealand is a dramatic
      example of how humans can alter landscapes through fire. However, evidence
      linking early human presence and land-cover change is inferential in most
      continental sites. We employed a multi-proxy approach to reconstruct
      anthropogenic land use in New Zealand's South Island over the last millennium
      using fecal and plant sterols as indicators of human activity and monosaccharide
      anhydrides, polycyclic aromatic hydrocarbons, charcoal and pollen as tracers of
      fire and vegetation change in lake-sediment cores. Our data provide a direct
      record of local human presence in Lake Kirkpatrick and Lake Diamond watersheds at
      the time of deforestation and a new and stronger case of human agency linked with
      forest clearance. The first detection of human presence matches charcoal and
      biomarker evidence for initial burning at c. AD 1350. Sterols decreased shortly
      after to values suggesting the sporadic presence of people and then rose to
      unprecedented levels after the European settlement. Our results confirm that
      initial human arrival in New Zealand was associated with brief and intense
      burning activities. Testing our approach in a context of well-established fire
      history provides a new tool for understanding cause-effect relationships in more
      complex continental reconstructions.

PMID- 30108238
TI  - The Streptococcus pyogenes fibronectin/tenascin-binding protein PrtF.2
      contributes to virulence in an influenza superinfection.
AB  - Influenza A virus (IAV) and Streptococcus pyogenes (the group A Streptococcus;
      GAS) are important contributors to viral-bacterial superinfections, which result
      from incompletely defined mechanisms. We identified changes in gene expression
      following IAV infection of A549 cells. Changes included an increase in
      transcripts encoding proteins with fibronectin-type III (FnIII) domains, such as
      fibronectin (Fn), tenascin N (TNN), and tenascin C (TNC). We tested the idea that
      increased expression of TNC may affect the outcome of an IAV-GAS superinfection.
      To do so, we created a GAS strain that lacked the Fn-binding protein PrtF.2. We
      found that the wild-type GAS strain, but not the mutant, co-localized with TNC
      and bound to purified TNC. In addition, adherence of the wild-type strain to IAV
      infected A549 cells was greater compared to the prtF.2 mutant. The wild-type
      strain was also more abundant in the lungs of mice 24 hours after superinfection
      compared to the mutant strain. Finally, all mice infected with IAV and the prtF.2
      mutant strain survived superinfection compared to only 42% infected with IAV and
      the parental GAS strain, indicating that PrtF.2 contributes to virulence in a
      murine model of IAV-GAS superinfection.

PMID- 30108239
TI  - A Methodological Assessment and Characterization of Genetically-Driven Variation
      in Three Human Phosphoproteomes.
AB  - Phosphorylation of proteins on serine, threonine, and tyrosine residues is a
      ubiquitous post-translational modification that plays a key part of essentially
      every cell signaling process. It is reasonable to assume that inter-individual
      variation in protein phosphorylation may underlie phenotypic differences, as has
      been observed for practically any other molecular regulatory phenotype. However,
      we do not know much about the extent of inter-individual variation in
      phosphorylation because it is quite challenging to perform a quantitative high
      throughput study to assess inter-individual variation in any post-translational
      modification. To test our ability to address this challenge with SILAC-based mass
      spectrometry, we quantified phosphorylation levels for three genotyped human cell
      lines within a nested experimental framework, and found that genetic background
      is the primary determinant of phosphoproteome variation. We uncovered multiple
      functional, biophysical, and genetic associations with germline driven
      phosphopeptide variation. Variants affecting protein levels or structure were
      among these associations, with the latter presenting, on average, a stronger
      effect. Interestingly, we found evidence that is consistent with a phosphopeptide
      variability buffering effect endowed from properties enriched within longer
      proteins. Because the small sample size in this 'pilot' study may limit the
      applicability of our genetic observations, we also undertook a thorough technical
      assessment of our experimental workflow to aid further efforts. Taken together,
      these results provide the foundation for future work to characterize inter
      individual variation in post-translational modification levels and reveal novel
      insights into the nature of inter-individual variation in phosphorylation.

PMID- 30108241
TI  - Fundamental pharmacological expressions on ocular exposure to capsaicin, the
      principal constituent in pepper sprays.
AB  - Eye irritation assessment is compulsory to anticipate health risks in military
      personnel exposed to riot control agents such as capsaicin, the principal
      constituent of oleoresin capsicum, or pepper sprays. The present work
      investigates certain fundamental yet unaddressed pharmacological manifestations
      on ocular exposure to capsaicin. Ocular pharmacology of capsaicin was studied
      using acute eye irritation (AEI), bovine corneal opacity and permeability (BCOP)
      assay, corneal fluorescein staining and indirect ophthalmoscopy studies,
      transcorneal permeation, Schirmer tear secretion test, nerve conduction velocity
      study and enzyme-linked immunosorbent assay (ELISA). Additionally, histopathology
      and scanning electron microscopy (SEM) of bovine corneas and rat optic nerves
      were done to further estimate capsaicin induced morphological variations. Our
      findings demonstrated that AEI, BCOP, corneal fluorescein staining and indirect
      ophthalmoscopy were useful in assessing capsaicin induced ocular irritation; AEI
      and BCOP also contributed towards indicating the eye irritation potential of
      capsaicin as per the United Nations Globally Harmonized System of Classification
      and Labelling of Chemicals categorization. Additional experimental observations
      include considerable transcorneal permeation of capsaicin, capsaicin induced
      reduction in tear secretions and nerve conduction velocity and increased
      expression of proinflammatory cytokines by ELISA. Histopathology and SEM were
      favourable techniques for the detection of capsaicin induced ocular physiological
      modifications.

PMID- 30108243
TI  - Biochemical analysis of GTPase FlhF which controls the number and position of
      flagellar formation in marine Vibrio.
AB  - FlhF controls the number and position of the polar flagellar formation of Vibrio
      species. FlhF, is a paralog of FtsY, a GTPase acting in the Sec membrane
      transport system of bacteria, and localizes at the cell pole. Mutations in the
      conserved GTPase motif of FlhF lost polar localization capability and flagellar
      formation. Vibrio FlhF has not, until now, been purified as soluble protein.
      Here, we report that addition of MgCl2 and GTP or GDP at the step of cell lysis
      greatly improved the solubility of FlhF, allowing us to purify it in homogeneity.
      Purified FlhF showed GTPase activity only in the presence of FlhG. Of twelve FlhF
      GTPase motif mutants showing reduced function, eleven were recovered as
      precipitate after the cell disruption. The E440K substitution could be purified
      and showed no GTPase activity even in the presence of FlhG. Interestingly an FlhF
      substitution in the putative catalytic residue for GTP hydrolysis, R334A, allowed
      normal flagellar formation although GTPase activity of FlhF was completely
      abolished. Furthermore, size exclusion chromatography of purified FlhF revealed
      that it forms dimers in the presence of GTP but exists as monomer in the presence
      of GDP. We speculate that the GTP binding allows FlhF to dimerize and localize at
      the pole where it initiates flagellar formation, and the GDP-bound form diffuses
      as monomer.

PMID- 30108242
TI  - REST overexpression in mice causes deficits in spontaneous locomotion.
AB  - Overexpression of REST has been implicated in brain tumors, ischemic insults,
      epilepsy, and movement disorders such as Huntington's disease. However, owing to
      the lack of a conditional REST overexpression animal model, the mechanism of
      action of REST overexpression in these disorders has not been established in
      vivo. We created a REST overexpression mouse model using the human REST (hREST)
      gene. Our results using these mice confirm that hREST expression parallels
      endogenous REST expression in embryonic mouse brains. Further analyses indicate
      that REST represses the dopamine receptor 2 (Drd2) gene, which encodes a critical
      nigrostriatal receptor involved in regulating movement, in vivo. Overexpression
      of REST using Drd2-Cre in adult mice results in increased REST and decreased DRD2
      expression in the striatum, a major site of DRD2 expression, and phenocopies the
      spontaneous locomotion deficits seen upon global DRD2 deletion or specific DRD2
      deletion from indirect-pathway medium spiny neurons. Thus, our studies using this
      mouse model not only reveal a new function of REST in regulating spontaneous
      locomotion but also suggest that REST overexpression in DRD2-expressing cells
      results in spontaneous locomotion deficits.

PMID- 30108244
TI  - Statistical Evidence for the Role of Southwestern Indian Ocean Heat Content in
      the Indian Summer Monsoon Rainfall.
AB  - This study examines the benefit of using Ocean Mean Temperature (OMT) to aid in
      the prediction of the sign of Indian Summer Monsoon Rainfall (ISMR) anomalies.
      This is a statistical examination, rather than a process study. The thermal
      energy needed for maintaining and intensifying hurricanes and monsoons comes from
      the upper ocean, not just from the thin layer represented by sea surface
      temperature (SST) alone. Here, we show that the southwestern Indian OMT down to
      the depth of the 26  degrees C isotherm during January-March is a better
      qualitative predictor of the ISMR than SST. The success rate in predicting above-
      or below-average ISMR is 80% for OMT compared to 60% for SST. Other January-March
      mean climate indices (e.g., NINO3.4, Indian Ocean Dipole Mode Index, El Nino
      Southern Oscillation Modoki Index) have less predictability (52%, 48%, and 56%,
      respectively) than OMT percentage deviation (PD) (80%). Thus, OMT PD in the
      southwestern Indian Ocean provides a better qualitative prediction of ISMR by the
      end of March and indicates whether the ISMR will be above or below the
      climatological mean value.

PMID- 30108245
TI  - Understanding the Mechanism of Action of the Anti-Dandruff Agent Zinc Pyrithione
      against Malassezia restricta.
AB  - Dandruff is known to be associated with Malassezia restricta. Zinc pyrithione
      (ZPT) has been used as an ingredient in anti-dandruff treatments. The mechanism
      of ZPT has been investigated in several studies; however, a non-pathogenic model
      yeast, such as Saccharomyces cerevisiae was most often used. The aim of the
      present study was to understand how ZPT inhibits the growth of M. restricta. We
      analyzed the cellular metal content and transcriptome profile of ZPT-treated M.
      restricta cells and found that ZPT treatment dramatically increased cellular zinc
      levels, along with a small increase in cellular copper levels. Moreover, our
      transcriptome analysis showed that ZPT inhibits Fe-S cluster synthesis in M.
      restricta. We also observed that ZPT treatment significantly reduced the
      expression of lipases, whose activities contribute to the survival and virulence
      of M. restricta on human skin. Therefore, the results of our study suggest that
      at least three inhibitory mechanisms are associated with the action of ZPT
      against M. restricta: (i) an increase in cellular zinc levels, (ii) inhibition of
      mitochondrial function, and (iii) a decrease in lipase expression.

PMID- 30108246
TI  - The urinary microbiome associated with bladder cancer.
AB  - Recent findings suggest that human microbiome can influence the development of
      cancer, but the role of microorganisms in bladder cancer pathogenesis has not
      been explored yet. The aim of this study was to characterize and compare the
      urinary microbiome of bladder cancer patients with those of healthy controls.
      Bacterial communities present in urine specimens collected from 12 male patients
      diagnosed with bladder cancer, and from 11 healthy, age-matched individuals were
      analysed using 16S sequencing. Our results show that the most abundant phylum in
      both groups was Firmicutes, followed by Actinobacteria, Bacteroidetes and
      Proteobacteria. While microbial diversity and overall microbiome composition were
      not significantly different between groups, we could identify operational
      taxonomic units (OTUs) that were more abundant in either group. Among those that
      were significantly enriched in the bladder cancer group, we identified an OTU
      belonging to genus Fusobacterium, a possible protumorigenic pathogen. In an
      independent sample of 42 bladder cancer tissues, 11 had Fusobacterium nucleatum
      sequences detected by PCR. Three OTUs from genera Veillonella, Streptococcus and
      Corynebacterium were more abundant in healthy urines. However, due to the limited
      number of participants additional studies are needed to determine if urinary
      microbiome is associated with bladder cancer.

PMID- 30108247
TI  - Assessment of candidate elements for development of spectral photon-counting CT
      specific contrast agents.
AB  - Spectral photon-counting computed tomography (SPCCT) is a rapidly emerging
      imaging modality that provides energy-dependent information on individual x-ray
      photons, leading to accurate material decomposition and simultaneous
      quantification of multiple contrast generating materials. Development of SPCCT
      specific contrast agents is needed to overcome the issues with currently used
      iodinated contrast agents, such as difficulty in differentiation from calcified
      structures, and yield SPCCT's full promise. In this study, the contrast
      generation of different elements is investigated using a prototype SPCCT scanner
      based on a modified clinical CT system and suitable elements for novel contrast
      agent development for SPCCT imaging are identified. Furthermore, nanoparticles
      were synthesized from tantalum as a proof of concept spectral photon-counting CT
      agent and tested for their in vitro cytotoxicity and contrast generation to
      provide insight into the feasibility of nanoparticle contrast agent development
      from these elements. We found that gadolinium, ytterbium and tantalum generate
      high contrast in spectral photon-counting CT imaging and may be suitable elements
      for contrast agent development for this modality. Our proof of concept results
      with tantalum-based nanoparticles underscore this conclusion due to their
      detectability with spectral photon-counting CT, as well as their
      biocompatibility.

PMID- 30108249
TI  - Evidence Based Tailored Parotidectomy in Treating External Auditory Canal
      Carcinoma.
AB  - Carcinoma of the external auditory canal (EAC) is a rare tumor and little
      information is available regarding parotid gland in surgically treating EAC
      carcinomas. This study aimed to investigate the mode of parotid involvement in
      EAC carcinoma through staging and histopathological analysis, and to establish
      surgical guidelines for the parotid gland management when there is no clinical
      evidence of parotid involvement. Sixty-five patients with EAC carcinoma who
      underwent temporal bone resection and any type of parotidectomy simultaneously
      were retrospectively reviewed. The rate of direct parotid invasion and parotid
      nodal involvement was analyzed according to the stage and histopathological
      findings. Among the 65 patients, 39 were confirmed to have squamous cell
      carcinoma (SCC) and 26 were confirmed to have adenoid cystic carcinoma (ACC).
      Direct parotid invasion occurred in 7 of 39 patients with SCC, only in the
      advanced stages, and in 15 of 26 patients with ACC, regardless of stage.
      Metastasis to the parotid node was noted in 6 patients with advanced-stage SCC,
      whereas no patient with ACC showed parotid nodal metastasis. For adequate tumor
      control with low risk of surgical complications, evidence based tailored
      parotidectomy should be applied. With no evidence of parotid involvement, an
      elective parotidectomy can be excluded in early SCC, whereas a total
      parotidectomy is recommended for advanced SCC. In ACC, basal resection of the
      parotid gland rather than a superficial or total parotidectomy should be
      performed at all disease stages.

PMID- 30108248
TI  - Strong increase in the autofluorescence of cells signals struggle for survival.
AB  - Prokaryotic and eukaryotic cells exhibit an intrinsic natural fluorescence due to
      the presence of fluorescent cellular structural components and metabolites.
      Therefore, cellular autofluorescence (AF) is expected to vary with the metabolic
      states of cells. We examined how exposure to the different stressors changes the
      AF of Escherichia coli cells. We observed that bactericidal treatments increased
      green cellular AF, and that de novo protein synthesis was required for the
      observed AF increase. Excitation and emission spectra and increased expression of
      the genes from the flavin biosynthesis pathway, strongly suggested that flavins
      are major contributors to the increased AF. An increased expression of genes
      encoding diverse flavoproteins which are involved in energy production and ROS
      detoxification, indicates a cellular strategy to cope with severe stresses. An
      observed increase in AF under stress is an evolutionary conserved phenomenon as
      it occurs not only in cells from different bacterial species, but also in yeast
      and human cells.

PMID- 30108250
TI  - Revelation of early detection of co-seismic ionospheric perturbations in GPS-TEC
      from realistic modelling approach: Case study.
AB  - GPS-derived Total Electron Content (TEC) is an integrated quantity; hence it is
      difficult to relate the detection of ionospheric perturbations in TEC to a
      precise altitude. As TEC is weighted by the maximum ionospheric density, the
      corresponding altitude (hmF2) is, generally, assumed as the perturbation
      detection altitude. To investigate the validity of this assumption in detail, we
      conduct an accurate analysis of the GPS-TEC measured early ionospheric signatures
      related to the vertical surface displacement of the Mw 7.4 Sanriku-Oki earthquake
      (Sanriku-Oki Tohoku foreshock). Using 3D acoustic ray tracing model to describe
      the evolution of the propagating seismo-acoustic wave in space and time, we
      demonstrate how to infer the detection altitude of these early signatures in TEC.
      We determine that the signatures can be detected at altitudes up to ~130 km below
      the hmF2. This peculiar behaviour is attributed to the satellite line of sight
      (LOS) geometry and station location with respect to the source, which allows one
      to sound the co-seismic ionospheric signatures directly above the rupture area.
      We show that the early onset times correspond to crossing of the LOS with the
      acoustic wavefront at lower ionospheric altitudes. To support the proposed
      approach, we further reconstruct the seismo-acoustic induced ionospheric
      signatures for a moving satellite in the presence of a geomagnetic field. Both
      the 3D acoustic ray tracing model and the synthetic waveforms from the 3D coupled
      model substantiate the observed onset time of the ionospheric signatures.
      Moreover, our simple 3D acoustic ray tracing approach allows one to extend this
      analysis to azimuths different than that of the station-source line.

PMID- 30108251
TI  - The role of Prefrontal Cortex in a Battle of the Sexes Dilemma involving a
      Conflict between Tribal and Romantic love.
AB  - The neural basis of dilemmas involving decisions with profound affective impact,
      such as in romantic life, remains to be understood. The "Battle of the Sexes" is
      a paradigm from Game Theory that can be used to experimentally address such
      dilemmas. A form of in-group love, tribal love in football fans, provides the
      opportunity to study strong affective dilemmas when tribal and romantic love
      compete for hedonic decision-making. Here, we used for the first time a "Battle
      of the Sexes" dilemma using fMRI. We investigated, in 44 male football fans, the
      neural correlates of cooperative behaviour under conflicting choices in the
      context of romantic versus tribal love. We identified a critical functional
      segregation of prefrontal regions in affective decision-making. The orbitofrontal
      cortex signalled emotional appraisal of the dilemma. The medial anterolateral and
      the ventromedial prefrontal cortices reflected reciprocal cooperation instead of
      selfish engagement in football-related activities. The lateral portion of
      anterolateral prefrontal cortex was recruited during ultimate deliberation. In
      sum, emotional appraisal and rational choice reflected a contiguous functional
      parcellation in anterolateral prefrontal cortex: appraisal (medial) vs. choice
      (lateral region).

PMID- 30108252
TI  - Cross-sectional and longitudinal analyses of outdoor air pollution exposure and
      cognitive function in UK Biobank.
AB  - Observational studies have shown consistently increased likelihood of dementia or
      mild cognitive impairment diagnoses in people with higher air pollution exposure
      history, but evidence has been less consistent for associations with cognitive
      test performance. We estimated the association between baseline neighbourhood
      level exposure to airborne pollutants (particulate matter and nitrogen oxides)
      and (1) cognitive test performance at baseline and (2) cognitive score change
      between baseline and 2.8-year follow-up, in 86,759 middle- to older-aged adults
      from the UK Biobank general population cohort. Unadjusted regression analyses
      indicated small but consistent negative associations between air pollutant
      exposure and baseline cognitive performance. Following adjustment for a range of
      key confounders, associations were inconsistent in direction and of very small
      magnitude. The largest of these indicated that 1 interquartile range higher air
      pollutant exposure was associated on average with 0.35% slower reaction time (95%
      CI: 0.13, 0.57), a 2.92% higher error rate on a visuospatial memory test (95% CI:
      1.24, 4.62), and numeric memory scores that were 0.58 points lower (95% CI: 
      0.96, -0.19). Follow-up analyses of cognitive change scores did not show evidence
      of associations. The findings indicate that in this sample, which is five-fold
      larger than any previous cross-sectional study, the association between air
      pollution exposure and cognitive performance was weak. Ongoing follow-up of the
      UK Biobank cohort will allow investigation of longer-term associations into old
      age, including longitudinal tracking of cognitive performance and incident
      dementia outcomes.

PMID- 30108253
TI  - Keap1-MCM3 interaction is a potential coordinator of molecular machineries of
      antioxidant response and genomic DNA replication in metazoa.
AB  - Coordination of DNA replication and cellular redox homeostasis mechanisms is
      essential for the sustained genome stability due to the sensitivity of
      replicating DNA to oxidation. However, substantial gaps remain in our knowledge
      of underlying molecular pathways. In this study, we characterise the interaction
      of Keap1, a central antioxidant response regulator in Metazoa, with the
      replicative helicase subunit protein MCM3. Our analysis suggests that structural
      determinants of the interaction of Keap1 with its critical downstream target -
      Nrf2 master transactivator of oxidative stress response genes - may have evolved
      in evolution to mimic the conserved helix-2-insert motif of MCM3. We show that
      this has led to a competition between MCM3 and Nrf2 proteins for Keap1 binding,
      and likely recruited MCM3 for the competitive binding dependent modulation of
      Keap1 controlled Nrf2 activities. We hypothesise that such mechanism could help
      to adjust the Keap1-Nrf2 antioxidant response pathway according to the
      proliferative and replicative status of the cell, with possible reciprocal
      implications also for the regulation of cellular functions of MCM3. Altogether
      this suggests about important role of Keap1-MCM3 interaction in the cross-talk
      between replisome and redox homeostasis machineries in metazoan cells.

PMID- 30108254
TI  - Transgenic Tmc2 expression preserves inner ear hair cells and vestibular function
      in mice lacking Tmc1.
AB  - Recent work has demonstrated that transmembrane channel-like 1 protein (TMC1) is
      an essential component of the sensory transduction complex in hair cells of the
      inner ear. A closely related homolog, TMC2, is expressed transiently in the
      neonatal mouse cochlea and can enable sensory transduction in Tmc1-null mice
      during the first postnatal week. Both TMC1 and TMC2 are expressed at adult stages
      in mouse vestibular hair cells. The extent to which TMC1 and TMC2 can substitute
      for each other is unknown. Several biophysical differences between TMC1 and TMC2
      suggest these proteins perform similar but not identical functions. To
      investigate these differences, and whether TMC2 can substitute for TMC1 in mature
      hair cells, we generated a knock-in mouse model allowing Cre-inducible expression
      of Tmc2. We assayed for changes in hair cell sensory transduction and auditory
      and vestibular function in Tmc2 knockin mice (Tm[Tmc2]) in the presence or
      absence of endogenous Tmc1, Tmc2 or both. Our results show that expression of
      Tm[TMC2] restores sensory transduction in vestibular hair cells and transiently
      in cochlear hair cells in the absence of TMC1. The cellular rescue leads to
      recovery of balance but not auditory function. We conclude that TMC1 provides
      some additional necessary function, not provided by TMC2.

PMID- 30108255
TI  - Impact of herbivory and competition on lake ecosystem structure: underwater
      experimental manipulation.
AB  - Two basic ecological relationships, herbivory and competition, distinctively
      influence terrestrial ecosystem characteristics, such as plant cover, species
      richness and species composition. We conducted a cage experiment under natural
      conditions in an aquatic ecosystem to test the impacts of two treatments combined
      in a factorial manner: (i) a pulse treatment - removal of dominant competitors
      among primary producers (macroalgae Chara sp. and Vaucheria sp.), and (ii) a
      press treatment - preventing herbivore (fish, crayfish) access to caged plots.
      The plots were sampled once before the treatments were established and four more
      times within two years. Both treatments had a significantly positive impact on
      macrophyte cover and species richness and changed the macrophyte species
      composition. The effect of the macroalgae removal was immediate with the highest
      species richness occurrence during the first post-treatment monitoring, but the
      positive effect vanished with time. In contrast, preventing herbivore access had
      a gradual but long-lasting effect and reached a more steady-state over time. Two
      of the most common species showed contrasting responses, the palatable
      Potamogeton pectinatus was most supported by caging, while the distasteful
      Myriophyllum spicatum preferred open plots. Our findings may be applicable during
      the revitalisation of aquatic ecosystems that aims to increase macrophyte
      biodiversity.

PMID- 30108256
TI  - Multi-marker metabarcoding approach to study mesozooplankton at basin scale.
AB  - Zooplankton plays a pivotal role in marine ecosystems and the characterisation of
      its biodiversity still represents a challenge for marine ecologists. In this
      study, mesozooplankton composition from 46 samples collected in summer along the
      western Adriatic Sea, was retrieved by DNA metabarcoding analysis. For the first
      time, the highly variable fragments of the mtDNA COI and the V9 region of 18S
      rRNA genes were used in a combined matrix to compile an inventory of
      mesozooplankton at basin scale. The number of sequences retrieved after quality
      filtering were 824,148 and 223,273 for COI and 18S (V9), respectively. The
      taxonomical assignment against reference sequences, using 95% (for COI) and 97%
      (for 18S) similarity thresholds, recovered 234 taxa. NMDS plots and cluster
      analysis divided coastal from offshore samples and the most representative
      species of these clusters were distributed according to the dominant surface
      current pattern of the Adriatic for the summer period. For selected sampling
      sites, mesozooplankton species were also identified under a stereo microscope
      providing insights on the strength and weakness of the two approaches. In
      addition, DNA metabarcoding was shown to be helpful for the monitoring of non
      indigenous marine metazoans and spawning areas of commercial fish species. We
      defined pros and cons of applying this approach at basin scale and the benefits
      of combining the datasets from two genetic markers.

PMID- 30108257
TI  - Isoform-Specific Compensation of Cyclooxygenase (Ptgs) Genes during Implantation
      and Late-Stage Pregnancy.
AB  - The participation of cyclooxygenase (COX) in embryo implantation and parturition
      has been studied extensively. However, the distinct role of the two COX isoforms
      in these processes still remains unclear. Using three characterized mouse lines
      where the Ptgs1 and Ptgs2 genes substitute for one another, this study focused on
      the reproductive significance of their distinct roles and potential biological
      substitution. In both non-gravid and gravid uteri, the knock-in COX-2 is
      expressed constitutively, whereas the knock-in COX-1 is slightly induced in early
      implantation. The delayed onset of parturition previously found in COX-1 null
      mice was corrected by COX-2 exchange in COX-2>COX-1 mice, with normal term
      pregnancy, gestation length and litter size. In contrast, loss of native COX-2 in
      COX-1>COX-2 mice resulted in severely impaired reproductive functions. Knock-in
      COX-1 failed to substitute for the loss of COX-2 in COX-1>COX-2 mice during
      implantation, indicating that COX-1 may be replaced by COX-2, but not vice versa.
      A panel of prostaglandins detected in uterus and ovary demonstrates that
      prostaglandin biosynthesis preferentially depends on native COX-1, but not COX-2.
      More interestingly, preferential compensations by the COX isoforms were sustained
      despite weak dependency on their role in prostaglandin biosynthesis in the uterus
      and ovary.

PMID- 30108258
TI  - Repeatability and reliability of exploratory behavior in proactive and reactive
      zebrafish, Danio rerio.
AB  - Behavioral responses to novel situations often vary and can belong to a suite of
      correlated behaviors. Characteristic behaviors of different personality types
      (e.g. stress coping styles) are generally consistent across contexts and time.
      Here, we compare the repeatability and reliability of exploratory behaviors
      between zebrafish strains selectively bred to display contrasting behavioral
      responses to stressors that represent the proactive-reactive axis. Specifically,
      we measure exploratory behavior of individual fish in an open field test over
      five weeks. We quantified the stationary time, average swimming speed and time
      spent by a fish in the center area. We found a number of strain differences for
      each behavioral measure. Stationary time was the most repeatable and reliable
      measure for assessing proactive-reactive behavioral differences. Reactive
      zebrafish generally showed the highest reliability and repeatability of
      exploratory behavior compared to proactive zebrafish and a separate wild caught
      strain. Given the increased interest in the evolutionary consequences and
      proximate mechanisms of consistent individual differences, it will be important
      to continue to investigate how different selective pressures may influence
      expression of stress coping styles and their effects on the consistency of an
      animal's behavior.

PMID- 30108259
TI  - Targeting proinflammatory cytokines ameliorates calcifying phenotype conversion
      of vascular progenitors under uremic conditions in vitro.
AB  - Severe vascular calcification develops almost invariably in chronic kidney
      patients posing a substantial risk to quality of life and survival. This unmet
      medical need demands identification of novel therapeutic modalities. We aimed to
      pinpoint components of the uremic microenvironment triggering differentiation of
      vascular progenitors to calcifying osteoblast-like cells. In an unbiased
      approach, assessing the individual potency of 63 uremic retention solutes to
      enhance calcific phenotype conversion of vascular progenitor cells, the pro
      inflammatory cytokines IL-1beta and TNF-alpha were identified as the strongest
      inducers followed by FGF-2, and PTH. Pharmacologic targeting of these molecules
      alone or in combination additively antagonized pro-calcifying properties of sera
      from uremic patients. Our findings stress the importance of pro-inflammatory
      cytokines above other characteristic components of the uremic microenvironment as
      key mediators of calcifying osteoblastic differentiation in vascular progenitors.
      Belonging to the group of "middle-sized molecules", they are neither effectively
      removed by conventional dialysis nor influenced by established supportive
      therapies. Specific pharmacologic interventions or novel extracorporeal
      approaches may help preserve regenerative capacity and control vascular
      calcification due to uremic environment.

PMID- 30108260
TI  - Automated fluorescence intensity and gradient analysis enables detection of rare
      fluorescent mutant cells deep within the tissue of RaDR mice.
AB  - Homologous recombination (HR) events are key drivers of cancer-promoting
      mutations, and the ability to visualize these events in situ provides important
      information regarding mutant cell type, location, and clonal expansion. We have
      previously created the Rosa26 Direct Repeat (RaDR) mouse model wherein HR at an
      integrated substrate gives rise to a fluorescent cell. To fully leverage this in
      situ approach, we need better ways to quantify rare fluorescent cells deep within
      tissues. Here, we present a robust, automated event quantification algorithm that
      uses image intensity and gradient features to detect fluorescent cells in deep
      tissue specimens. To analyze the performance of our algorithm, we simulate
      fluorescence behavior in tissue using Monte Carlo methods. Importantly, this
      approach reduces the potential for bias in manual counting and enables
      quantification of samples with highly dense HR events. Using this approach, we
      measured the relative frequency of HR within a chromosome and between chromosomes
      and found that HR within a chromosome is more frequent, which is consistent with
      the close proximity of sister chromatids. Our approach is both objective and
      highly rapid, providing a powerful tool, not only to researchers interested in
      HR, but also to many other researchers who are similarly using fluorescence as a
      marker for understanding mammalian biology in tissues.

PMID- 30108262
TI  - Gene Ontology Enrichment Improves Performances of Functional Similarity of Genes.
AB  - There exists a plethora of measures to evaluate functional similarity (FS)
      between genes, which is a widely used in many bioinformatics applications
      including detecting molecular pathways, identifying co-expressed genes,
      predicting protein-protein interactions, and prioritization of disease genes.
      Measures of FS between genes are mostly derived from Information Contents (IC) of
      Gene Ontology (GO) terms annotating the genes. However, existing measures
      evaluating IC of terms based either on the representations of terms in the
      annotating corpus or on the knowledge embedded in the GO hierarchy do not
      consider the enrichment of GO terms by the querying pair of genes. The enrichment
      of a GO term by a pair of gene is dependent on whether the term is annotated by
      one gene (i.e., partial annotation) or by both genes (i.e. complete annotation)
      in the pair. In this paper, we propose a method that incorporate enrichment of GO
      terms by a gene pair in computing their FS and show that GO enrichment improves
      the performances of 46 existing FS measures in the prediction of sequence
      homologies, gene expression correlations, protein-protein interactions, and
      disease associated genes.

PMID- 30108261
TI  - Integrated analysis of lncRNA and mRNA expression in rainbow trout families
      showing variation in muscle growth and fillet quality traits.
AB  - Muscle yield and quality traits are important for the aquaculture industry and
      consumers. Genetic selection for these traits is difficult because they are
      polygenic and result from multifactorial interactions. To study the genetic
      architecture of these traits, phenotypic characterization of whole body weight
      (WBW), muscle yield, fat content, shear force and whiteness were measured in ~500
      fish representing 98 families from a growth-selected line. RNA-Seq was used to
      sequence the muscle transcriptome of different families exhibiting divergent
      phenotypes for each trait. We have identified 240 and 1,280 differentially
      expressed (DE) protein-coding genes and long noncoding RNAs (lncRNAs),
      respectively, in fish families exhibiting contrasting phenotypes. Expression of
      many DE lncRNAs (n = 229) was positively correlated with overlapping, neighboring
      or distantly located protein-coding genes (n = 1,030), resulting in 3,392
      interactions. Three DE antisense lncRNAs were co-expressed with sense genes known
      to impact muscle quality traits. Forty-four DE lncRNAs had potential sponge
      functions to miRNAs that affect muscle quality traits. This study (1) defines
      muscle quality associated protein-coding and noncoding genes and (2) provides
      insight into non-coding RNAs involvement in regulating growth and fillet quality
      traits in rainbow trout.

PMID- 30108263
TI  - Gingerol suppresses sepsis-induced acute kidney injury by modulating
      methylsulfonylmethane and dimethylamine production.
AB  - Acute kidney injury (AKI) and metabolic dysfunction are critical complications in
      sepsis syndrome; however, their pathophysiological mechanisms remain poorly
      understood. Therefore, we evaluated whether the pharmacological properties of 6
      gingerol (6G) and 10-gingerol (10G) could modulate AKI and metabolic disruption
      in a rat model of sepsis (faecal peritonitis). Animals from the sham and AKI
      groups were intraperitoneally injected with 6G or 10G (25 mg/kg). Septic AKI
      decreased creatinine clearance and renal antioxidant activity, but enhanced
      oxidative stress and the renal mRNA levels of tumour necrosis factor-alpha,
      interleukin-1beta, and transforming growth factor-beta. Both phenol compounds
      repaired kidney function through antioxidant activity related to decreased
      oxidative/nitrosative stress and proinflammatory cytokines. Metabolomics analysis
      indicated different metabolic profiles for the sham surgery group, caecal
      ligation and puncture model alone group, and sepsis groups treated with
      gingerols. 1H nuclear magnetic resonance analysis detected important increases in
      urinary creatine, allantoin, and dimethylglycine levels in septic rats. However,
      dimethylamine and methylsulfonylmethane metabolites were more frequently detected
      in septic animals treated with 6G or 10G, and were associated with increased
      survival of septic animals. Gingerols attenuated septic AKI by decreasing renal
      disturbances, oxidative stress, and inflammatory response through a mechanism
      possibly correlated with increased production of dimethylamine and
      methylsulfonylmethane.

PMID- 30108264
TI  - Quantitative analysis of retinal and choroidal microvascular changes in patients
      with diabetes.
AB  - The relationship between choroidal and retinal microvascular changes has not yet
      been well described, and there were limited data on diagnostic ability of optical
      coherence tomography (OCT)-derived vascular parameters for determining diabetic
      retinopathy (DR) progression. We quantitatively analyzed OCT-derived vascular
      parameters at superficial (SCP) and deep retinal capillary plexus (DCP), and
      choroid. We assessed foveal avascular zone (FAZ), vessel density, vessel length
      density, and choroidal vascularity index in conjunction with DR stage. In this
      study, patients with diabetes and healthy controls were retrospectively analyzed.
      One-hundred seventy-four eyes were divided into six groups as follows: Healthy
      controls, no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR,
      and proliferative DR. There were significant quantitative changes in retinal and
      choroidal vascular parameters with DR progression. The FAZ area and perimeter
      correlated positively with worsening DR severity; the FAZ circularity index,
      retinal vessel density, retinal vessel length density, and choroidal vascularity
      index correlated negatively with worsening severity. Among these, FAZ circulatory
      index demonstrated good diagnostic performance for DR. Our results cautiously
      suggest that functional circulatory disturbances in retinal and choroidal
      vasculatures occur before DR presents. As DR progresses, DCP retinal
      microvasculature changes precede SCP changes.

PMID- 30108265
TI  - In vitro performances of novel co-spray-dried azithromycin/rifampicin
      microparticles for Rhodococcus equi disease treatment.
AB  - This work was aimed at providing clues on the in vitro performances of novel
      azithromycin/rifampicin combinations, in the form of co-spray-dried
      microparticles (AZM/RIF MP), against Rhodococcus equi, an animal and emerging
      human pathogen found responsible for worrying zoonosis. Various AZM/RIF
      combinations were spray-dried and characterized for their morphology and size.
      Susceptibility studies included determination of MIC, MBC, Fractional
      Inhibitory/Bactericidal Concentration Indexes and intracellular activity in R.
      equi-infected THP-1 cells. Cytotoxicity was tested on BEAS-2B cells through MTT
      assay and combination index assessment for drug interaction. Spray-dried MP were
      collapsed and 3-10 times smaller than commercial powders. Drug combinations
      showed an enhancement of in vitro antibacterial activity with a remarkable
      synergistic bactericidal effect. Azithromycin MP and AZM/RIF MP 2:1 led to a CFU
      reduction of >90% up to 4 days after treatment at all tested concentrations (p =
      0.001) but AZM/RIF MP 2:1 were at least four-fold more potent than AZM MP alone.
      IC50 values of >100 mg/L supported low cytotoxicity of drug combinations and the
      combination index suggested an antagonistic toxic effect. Co-spray-drying
      enhanced powder dispersibility and solubility, which may improve bioavailability
      as well as provide administration alternatives. The novel AZM/RIF MP combinations
      could result a valid platform to develop new treatment strategies against R. equi
      infections in animals and humans.

PMID- 30108267
TI  - Strong beaming of microwave surface waves with complementary split-ring-resonator
      arrays.
AB  - A thin copper sheet, populated by an array of complementary split ring
      resonators, presents strong surface wave beaming in orthogonal directions at two
      distinct frequencies. This simple array is significantly thinner than existing
      single frequency beaming surfaces. The observed beaming frequencies are
      associated with the two lowest resonance modes of the split rings, and the beams
      are subwavelength in width and approximately non-diverging. The beaming is
      analysed through comparison of near-field scans of the surface-normal electric
      fields with numerical simulations.

PMID- 30108266
TI  - Lateralization influences contest behaviour in domestic pigs.
AB  - Cerebral lateralization, i.e. hemispheric asymmetries in structure and function,
      relates in many species to a preference to attack from their left. Lateralization
      increases cognitive capacity, enabling the simultaneous processing of multiple
      sources of information. Therefore, lateralization may constitute a component of
      fighting ability (Resource Holding Potential), and/or influence the efficiency of
      information-gathering during a contest. We hypothesized that lateralization will
      affect contest outcome and duration, with an advantage for more strongly
      lateralized individuals. In 52 dyadic contests between weight-matched pigs (Sus
      scrofa; n = 104; 10 wk age), the direction of orientation towards the opponent
      was scan sampled every 10 s. Laterality indexes (LI) were calculated for the
      direction and strength of lateralization. Up to 12.5% of the individuals showed
      significant lateralization towards either the right or left but lateralization
      was absent at the population level. In line with our hypothesis, animals showing
      strong lateralization (irrespective of direction) had a shorter contest duration
      than animals showing weak lateralization. Winners did not differ from losers in
      their strength or direction of lateralization. Overall the results suggest that
      cerebral lateralization may aid in conflict resolution, but does not directly
      contribute to fighting ability, and will be of value in the study of animal
      contests.

PMID- 30108268
TI  - A Mixture of Atropisomers Enhances Neutral Lipid Degradation in Mammalian Cells
      with Autophagy Induction.
AB  - Atropisomers with a biaryl dihydronaphthopyranone structure, dinapinones A1
      (DPA1) (M position) and A2 (DPA2) (P position), were isolated from the fungus
      culture broth of Talaromyces pinophilus FKI-3864 as inhibitors of [14C]neutral
      lipid ([14C]triacylglycerol (TG) and [14C]cholesteryl ester (CE)) synthesis from
      [14C]oleic acid in Chinese hamster ovary-K1 (CHO-K1) cells. DPA2 inhibited
      [14C]TG and [14C]CE synthesis (IC50s, 0.65 and 5.6 MUM, respectively), but DPA1
      had no inhibitory activity on [14C]TG and [14C]CE synthesis even at 12 MUM.
      However, a 1:1 mixture of DPA1 and DPA2 (DPAmix) had the most potent inhibitory
      activity on [14C]TG and [14C]CE synthesis (IC50s, 0.054 and 0.18 MUM,
      respectively). The mechanism of action of DPAmix was investigated. DPAmix had no
      effects on the enzymes involved in neutral lipid synthesis, while DPAmix enhanced
      the degradation of [14C]neutral lipids with concomitant decrease in cytosolic
      lipid droplets accumulated in CHO-K1 cells. From analysis of autophagy marker
      proteins, DPAmix caused dose-dependent induction of microtubule-associated
      protein light chain 3-II (LC3-II) and degradation of p62. In the autophagic flux
      assay using bafilomycin A1, DPAmix upregulated autophagosome turnover. These
      results reveal that DPAmix enhances neutral lipid degradation together with
      induction of autophagy.

PMID- 30108270
TI  - Non-linear longitudinal associations between moderate-to-vigorous physical
      activity and adiposity across the adiposity distribution during childhood and
      adolescence: Gateshead Millennium Study.
AB  - OBJECTIVE: Insufficient moderate-to-vigorous intensity physical activity (MVPA)
      is harmful for youth; however, the evidence for differential effects by weight
      status is limited. The study aimed to examine associations between MVPA and
      adiposity by weight status across childhood and adolescence. METHODS:
      Participants were from the Gateshead Millennium Study. Physical activity and body
      composition measures were taken at age 7 y (n = 502; measures taken between
      October 2006 and December 2007), 9 y (n = 506; October 2008-September 2009), 12 y
      (n = 420; October 2011-September 2012), and 15 y (n = 306; September 2014
      September 2015). Participants wore an ActiGraph GT1M and epochs were classified
      as MVPA when accelerometer counts were >=574 counts/15 s. Weight and height were
      measured using standardized methods and fat mass using bioelectrical impedance.
      Associations between MVPA and changes in BMI and FMI were examined by weight
      status using quantile regression. RESULTS: Higher MVPA was associated with lower
      FMI for the 25th, 50th, 75th, and 90th percentile and lower BMI at the 50th,
      75th, and 90th percentile, independent of accelerometer wear time, sex, and
      sedentary time. The association between MVPA and change in adiposity was stronger
      in the higher than lower FMI and BMI percentiles (e.g., 1 h/day more MVPA was
      associated with a 1.5 kg/m2 and 2.7 kg/m2 lower FMI at the 50th and 90th FMI
      percentiles, respectively). CONCLUSIONS: The effect of MVPA on adiposity in the
      higher adiposity percentiles is stronger than reported to date. Given overweight
      and obese children are the highest risk group for later obesity, targeting MVPA
      might be a particularly effective obesity prevention strategy.

PMID- 30108269
TI  - Do worse baseline risk factors explain the association of healthy obesity with
      increased mortality risk? Whitehall II Study.
AB  - OBJECTIVE: To describe 20-year risk factor trajectories according to initial
      weight/health status and investigate the extent to which baseline differences
      explain greater mortality among metabolically healthy obese (MHO) individuals
      than healthy non-obese individuals. METHODS: The sample comprised 6529
      participants in the Whitehall II study who were measured serially between 1991
      1994 and 2012-2013. Baseline weight (non-obese or obese; body mass index (BMI)
      >=30 kg/m2) and health status (healthy or unhealthy; two or more of hypertension,
      low high-density lipoprotein cholesterol (HDL-C), high triglycerides, high
      glucose, and high homeostatic model assessment of insulin resistance (HOMA-IR))
      were defined. The relationships of baseline weight/health status with 20-year
      trajectories summarizing ~25,000 observations of systolic and diastolic blood
      pressures, HDL-C, triglycerides, glucose, and HOMA-IR were investigated using
      multilevel models. Relationships of baseline weight/health status with all-cause
      mortality up until July 2015 were investigated using Cox proportional hazards
      regression. RESULTS: Trajectories tended to be consistently worse for the MHO
      group compared to the healthy non-obese group (e.g., glucose by 0.21 (95% CI
      0.09, 0.33; p < 0.001) mmol/L at 20-years of follow-up). Consequently, the MHO
      group had a greater risk of mortality (hazard ratio 2.11 (1.24, 3.58; p = 0.006))
      when the referent group comprised a random sample of healthy non-obese
      individuals. This estimate, however, attenuated (1.34 (0.85, 2.13; p = 0.209))
      when the referent group was matched to the MHO group on baseline risk factors.
      CONCLUSIONS: Worse baseline risk factors may explain any difference in mortality
      risk between obese and non-obese groups both labelled as healthy, further
      challenging the concept of MHO.

PMID- 30108273
TI  - In vivo delivery of pPERDBY to BALB/c mice by LacVax(r) DNA-I and comparison of
      elicited immune response with conventional immunization methods.
AB  - The non-invasive food grade Lactococcus lactis (L. lactis) represents a safe and
      attractive alternative to invasive pathogens for the delivery of plasmid DNA at
      mucosal sites. We have earlier shown the DNA delivery potential of r-L. lactis
      harboring DNA vaccine reporter plasmid; pPERDBY in vitro. In the present work, we
      examined in vivo delivery potential of food grade non-invasive r-L.
      lactis::pPERDBY (LacVax(r) DNA-I) in BALB/c mice. Moreover, using EGFP as a model
      antigen, we also characterized and compared the immune response elicited by
      LacVax(r) DNA-I with other conventional vaccination approaches using protein and
      naked DNA immunization. The presence of antigen-specific serum IgG and fecal
      secretory IgA (sIgA) antibodies demonstrated in vivo DNA delivery and immune
      elicitation potential of the developed LacVax(r) DNA-I. As compared with
      intramuscular injection, oral delivery of pPERDBY via L. lactis resulted in a
      significantly rapid increase in IgG and higher sIgA titers, indicating the
      immunogenic and immunostimulatory properties of the LacVax(r) DNA-I. The needle
      free immunization with LacVax(r) DNA-I led to increased production of IL-4, an
      indicator of Th2 screwed response. To the best of our knowledge, this report for
      the first time outlines comparison of orally administered LacVax(r) DNA-I with
      other conventional vaccination approaches.

PMID- 30108272
TI  - Dual action of the Galphaq-PLCbeta-PI(4,5)P2 pathway on TRPC1/4 and TRPC1/5
      heterotetramers.
AB  - The transient receptor potential canonical (TRPC) 1 channel is widely distributed
      in mammalian cells and is involved in many physiological processes. TRPC1 is
      primarily considered a regulatory subunit that forms heterotetrameric channels
      with either TRPC4 or TRPC5 subunits. Here, we suggest that the regulation of
      TRPC1/4 and TRPC1/5 heterotetrameric channels by the Galphaq-PLCbeta pathway is
      self-limited and dynamically mediated by Galphaq and PI(4,5)P2. We provide
      evidence indicating that Galphaq protein directly interacts with either TRPC4 or
      TRPC5 of the heterotetrameric channels to permit activation. Simultaneously,
      Galphaq-coupled PLCbeta activation leads to the breakdown of PI(4,5)P2, which
      inhibits activity of TRPC1/4 and 1/5 channels.

PMID- 30108271
TI  - A Swath Label-Free Proteomics insight into the Faah-/- Mouse Liver.
AB  - Fatty acid amide hydrolase (FAAH) is an important enzyme for lipid metabolism and
      an interesting pharmacological target, given its role in anandamide breakdown.
      The FAAH-/- genotype is the most widely used mouse model to investigate the
      effects of a complete pharmacological inhibition of this enzyme. In this paper,
      we explore, by means of label-free SWATH proteomics, the changes in protein
      expression occurring in the liver of FAAH-/- knockout (KO) mice. We identified
      several altered biological processes and pathways, like fatty acid synthesis and
      glycolysis, which explain the observed phenotype of this mouse. We also observed
      the alteration of other proteins, like carboxylesterases and S
      methyltransferases, apparently not immediately related to FAAH, but known to have
      important biological roles. Our study, reporting more than 3000 quantified
      proteins, offers an in-depth analysis of the liver proteome of this model.

PMID- 30108274
TI  - Oxidative stress decreases the redox ratio and folate content in the gut microbe,
      Enterococcus durans (MTCC 3031).
AB  - Gut microbiome plays an important role in determining the effectiveness of cancer
      therapy. The composition of the microbiome is crucial to maintain good digestive
      health in the host, and to prevent and treat colorectal cancers. Most cancer
      therapies employ oxidative stress, which disturbs the redox status of the cell,
      and consequently affect growth, reductive biosynthesis and cell death. Therefore,
      oxidative stress can undesirably affect the gut microbiome. Hence, it is
      important to understand the impact of oxidative stress on gut bacteria to devise
      effective treatment strategies. The current study induces oxidative stress in the
      model gut bacterium Enterococcus durans (MTCC 3031) with menadione and H2O2.
      Oxidative stress considerably decreased the redox ratio (NADPH/NADP), an
      indicator of the redox status, by 55% (menadione) and 28% (H2O2). In addition, an
      oxidative stress induced decrease in redox ratio decreased folate synthesis by
      the bacteria, which is an undesirable consequence for the host, since folate
      deficiency can induce colorectal cancer. Further, oxidative stress considerably
      decreased growth and the biomass density by 61% (menadione) and 21% (H2O2). Thus,
      maintenance of the cellular redox status and management of oxidative stress in
      the gut microbiome may be crucial to the effectiveness of cancer treatment
      strategies.

PMID- 30108275
TI  - Integrative metagenomic and biochemical studies on rifamycin ADP
      ribosyltransferases discovered in the sediment microbiome.
AB  - Antibiotic resistance is a serious and growing threat to human health. The
      environmental microbiome is a rich reservoir of resistomes, offering
      opportunities to discover new antibiotic resistance genes. Here we demonstrate an
      integrative approach of utilizing gene sequence and protein structural
      information to characterize unidentified genes that are responsible for the
      resistance to the action of rifamycin antibiotic rifampin, a first-line
      antimicrobial agent to treat tuberculosis. Biochemical characterization of four
      environmental metagenomic proteins indicates that they are adenosine diphosphate
      (ADP)-ribosyltransferases and effective in the development of resistance to FDA
      approved rifamycins. Our analysis suggests that even a single residue with low
      sequence conservation plays an important role in regulating the degrees of
      antibiotic resistance. In addition to advancing our understanding of antibiotic
      resistomes, this work demonstrates the importance of an integrative approach to
      discover new metagenomic genes and decipher their biochemical functions.

PMID- 30108277
TI  - Nanohydroxyapatite/polyamide 66 strut subsidence after one-level corpectomy:
      underlying mechanism and effect on cervical neurological function.
AB  - The aim of this study was to investigate n-HA/PA66 strut subsidence after one
      level in Anterior cervical corpectomy decompression and fusion (ACCF) and its
      effect on treatment outcomes to better understand the underlying mechanism and
      related risk factors. In total, 56 patients undergoing ACCF using n-HA/PA66
      struts were analysed retrospectively. After a 12-month follow-up, the height of
      the fused segments and fused intervertebral heights were measured, the
      neurological findings were evaluated using the Japanese Orthopedic Association
      (JOA) and axial pain was assessed using a Visual Analogue Scale(VAS). Subsidence
      was defined as a decrease in the height of the fused segments or the fused
      intervertebral body greater than 3 mm compared with that on postoperative day
      one, and all patients were assigned to the n-HA/PA66 strut subsidence and control
      groups. In total, 45 patients experienced n-HA/PA66 strut subsidence during the
      postoperative (3 +/- 2.42/3.11 +/- 2.01) months. No significant differences were
      observed in sex, age, hospitalization time, surgical haemorrhage,bone mineral
      density (BMD), or height in the n-HA/PA66 strut group. The JOA and VAS of neck
      pain in the control group improved more than those in the subsidence group,
      suggesting that subsidence might be correlated with poor improvement of
      neurological function. In conclusion, n-HA/PA66 strut subsidence is a common
      complication after ACCF, and the reduced height of the postoperative fused
      segments and the height reduction in the postoperative fused intervertebral
      bodies are independent risk factors of n-HA/PA66 strut subsidence.

PMID- 30108276
TI  - Effectiveness of Z-score of log-transformed A Body Shape Index (LBSIZ) in
      predicting cardiovascular disease in Korea: the Korean Genome and Epidemiology
      Study.
AB  - Body mass index (BMI) and waist circumference (WC) have limitations in
      stratifying cardio-metabolic risks. Another obesity measure, A Body Shape Index
      (ABSI), has been introduced but its applicability remains limited. To address
      this, the z-score of the log-transformed ABSI (LBSIZ) was recently developed.
      This study aimed to examine the ability of LBSIZ, compared to that of WC and BMI,
      to predict cardiovascular disease (CVD) risk. The study included 8,485
      participants aged 40-69 years (mean age = 52.1) who were followed for 10 years
      and recruited from the Korean Genome and Epidemiology Study, a population-based
      cohort study. The area under the curve was 0.635 (95% confidence interval [CI]:
      0.614-0.657) for LBSIZ, 0.604 (95%CI: 0.580-0.627) for WC, and 0.538 (95%CI:
      0.514-0.562) for BMI. The AUC of the Framingham risk score (FRS) was 0.680
      (95%CI: 0.659-0.701) in comparison. When we added LBSIZ to the model, the
      integrated AUC significantly improved from 0.680 to 0.692 (95%CI: 0.672-0.713; p
      value, 0.033), whereas there were no changes with BMI (AUC, 0.678; 95%CI: 0.656
      0.699) or WC (AUC, 0.679; 95%CI: 0.658-0.701). In the multivariate Cox regression
      analysis, LBSIZ but not BMI or WC showed a significant hazard ratio of CVD event
      compared to 1st decile of each parameter. In the restricted cubic spline
      regression, BMI and WC showed an overall J-shaped relationship with CVD events
      whereas LBSIZ showed a linear relationship. LBSIZ is strongly associated with CVD
      risk and should predict CVD risk better than BMI and WC in the general
      population.

PMID- 30108279
TI  - Mechanisms of insulin resistance.

PMID- 30108280
TI  - Ketogenic diet, a potentially valuable therapeutic option for the management of
      refractory epilepsy in classical neonatal nonketotic hyperglycinemia: a case
      report.
AB  - Nonketotic hyperglycinemia (NKH) is a devastating inborn error of glycine
      metabolism caused by deficient activity of the glycine cleavage enzyme.
      Classically, patients present with lethargy, hypotonia, myoclonic jerks,
      transient respiratory depression in the first week of life and often progress to
      death. Surviving infants have profound psychomotor retardation, refractory
      epilepsy and poor quality of life. Currently, no effective therapeutic avenues
      exist for severe NKH. Ketogenic diet (KD) has been trialled only in a small group
      of patients with neonatal NKH and early myoclonic encephalopathy, in whom
      significant improvements in seizure control were reported. We describe an infant
      with classical neonatal NKH who presented on the third day of life with
      hypotonia, poor feeding, respiratory insufficiency resulting in ventilatory
      support and seizures with burst-suppression pattern on electroencephalogram
      (EEG). KD initiated at age 6 months for intractable seizures, lead to a dramatic
      decrease in seizure frequency, EEG improvements, normalisation of plasma glycine
      levels, reduced spasticity and improved quality of life. KD may be a valuable
      treatment modality for refractory seizure control in classical NKH.

PMID- 30108278
TI  - The complete methylome of an entomopathogenic bacterium reveals the existence of
      loci with unmethylated Adenines.
AB  - DNA methylation can serve to control diverse phenomena in eukaryotes and
      prokaryotes, including gene regulation leading to cell differentiation. In
      bacteria, DNA methylomes (i.e., methylation state of each base of the whole
      genome) have been described for several species, but methylome profile variation
      during the lifecycle has rarely been studied, and only in a few model organisms.
      Moreover, major phenotypic changes have been reported in several bacterial
      strains with a deregulated methyltransferase, but the corresponding methylome has
      rarely been described. Here we report the first methylome description of an
      entomopathogenic bacterium, Photorhabdus luminescens. Eight motifs displaying a
      high rate of methylation (>94%) were identified. The methylome was strikingly
      stable over course of growth, but also in a subpopulation responsible for a
      critical step in the bacterium's lifecycle: successful survival and proliferation
      in insects. The rare unmethylated GATC motifs were preferentially located in
      putative promoter regions, and most of them were methylated after Dam
      methyltransferase overexpression, suggesting that DNA methylation is involved in
      gene regulation. Our findings bring key insight into bacterial methylomes and
      encourage further research to decipher the role of loci protected from DNA
      methylation in gene regulation.

PMID- 30108281
TI  - EXploring practice gaps to improve PERIoperativE Nutrition CarE (EXPERIENCE
      Study): a qualitative analysis of barriers to implementation of evidence-based
      practice guidelines.
AB  - BACKGROUND/OBJECTIVES: Aligning care with best practice-such as Enhanced Recovery
      After Surgery (ERAS) guidelines-may improve patient outcomes. However,
      translating research into practice is challenging and implementation science
      literature emphasises the importance of understanding barriers and enablers
      specific to the local context and clinicians. This study aimed to explore staff
      perceptions about barriers and enablers to practice change aligning with
      nutrition-related recommendations from ERAS guidelines. SUBJECTS/METHODS: A
      qualitative study using a maximum variation sampling method. Clinicians involved
      in care of patients admitted to two general surgical wards consented to
      participate in semi-structured interviews. Framework analysis was undertaken
      using the integrated Promoting Action on Research Implementation in Health
      Services framework to identify a priori and emergent themes. RESULTS: From
      interviews with 13 clinicians (two surgical consultants, one registrar, one
      intern; one anaesthetist; two nurse unit managers, one surgical nurse
      coordinator, three nurses; two dietitians), three major themes were identified:
      (a) complexity of the context (e.g., unpredictable theatre times, requirement for
      flexibility and large, multidisciplinary workforce); (b) strong decision-making
      hierarchy, combined with lack of knowledge, confidence or authority of junior and
      non-surgical staff to implement change; and (c) poor communication and teamwork
      (within and between disciplines). These barriers culminate in practice where
      default behaviours are habit, and the view that achieving clinical consensus is
      challenging. CONCLUSIONS: This study highlights the necessity for a multifaceted
      implementation approach that simplifies the process, flattens the power
      differential and facilitates communication and teamwork. Other facilities may
      consider these findings when implementing similar practice change interventions.

PMID- 30108282
TI  - Linear isoforms of the long noncoding RNA CDKN2B-AS1 regulate the c-myc-enhancer
      binding factor RBMS1.
AB  - Variants in the long noncoding RNA (lncRNA) gene CDKN2B-AS1 (CDKN2B antisense RNA
      1; ANRIL) are genome-wide associated with type 2 diabetes (T2D), atherosclerosis,
      and several forms of cancer. However, it is currently not understood how CDKN2B
      AS1 transcripts translate into diabetes. We previously demonstrated trans
      regulation of the proximal polyadenylated transcripts on several genes with
      functions in glucose and lipid metabolism. However, information on specific genes
      that are regulated at physiological concentrations by the distal polyadenylated
      CDKN2B-AS1 transcripts is lacking. To identify target genes of CDKN2B-AS1 trans
      regulation, we designed inducible short hairpin RNA constructs and integrated
      them into the genome of T-Rex HEK293 cells. Changes of gene expression after
      induction were determined at defined time points by genome-wide mRNA expression
      analysis. We confirmed downregulation of RBMS1, located on chromosome 2 (RNA
      binding motif, single-stranded interacting protein 1) at the transcript and
      protein level in stable-transfected, inducible HeLa cells, and demonstrated that
      the effect was independent of the cell type, known cis-regulatory effects, and
      regulation of the proximal polyadenylated CDKN2B-AS1 isoforms. Direct binding of
      CDKN2B-AS1 transcripts to RBMS1 was shown by RNA immunoprecipitation. RBMS1
      encodes a cell cycle suppressor. We conclude that the distal and proximal
      polyadenylated CDKN2B-AS1 transcripts have separate functions in gene regulation,
      which are independent of the circular CDKN2B-AS1 isoforms and of the genes
      CDKN2A/2B.

PMID- 30108283
TI  - A study of Kibbutzim in Israel reveals risk factors for cardiometabolic traits
      and subtle population structure.
AB  - Genetic studies in isolated populations often increase power for identifying loci
      associated with complex diseases and traits. We present here the Kibbutzim Family
      Study (KFS), aimed at investigating the genetic basis of cardiometabolic traits
      in extended Israeli families characterized by long-term social stability and a
      homogeneous environment. Extensive information on cardiometabolic traits, as well
      as genome-wide genotypes, were collected on 901 individuals. We observed that
      most KFS participants were of Ashkenazi Jewish (AJ) genetic origin, confirmed a
      recent severe bottleneck in the AJ recent history, and detected a subtle within
      AJ population structure. Focusing on genetic variants relatively common in the
      KFS but very rare in Europeans, we observed that AJ-enriched variants appear in
      cancer-related pathways more than expected by chance. We conducted an association
      study of the AJ-enriched variants against 16 cardiometabolic traits, and found
      seven loci (24 variants) to be significantly associated. The strongest
      association, which we also replicated in an independent study, was between a
      variant upstream of MSRA (frequency ~1% in the KFS and nearly absent in
      Europeans) and weight (P = 3.6?10-8). In conclusion, the KFS is a valuable
      resource for the study of the population genetics of Israel as well as the
      genetics of cardiometabolic traits.

PMID- 30108284
TI  - Palaeozoic giant dragonflies were hawker predators.
AB  - The largest insects to have ever lived were the giant meganeurids of the Late
      Palaeozoic, ancient stem relatives of our modern dragonflies. With wingspans up
      to 71 cm, these iconic insects have been the subject of varied documentaries on
      Palaeozoic life, depicting them as patrolling for prey through coal swamp forests
      amid giant lycopsids, and cordaites. Such reconstructions are speculative as few
      definitive details of giant dragonfly biology are known. Most specimens of giant
      dragonflies are known from wings or isolated elements, but Meganeurites
      gracilipes preserves critical body structures, most notably those of the head.
      Here we show that it is unlikely it thrived in densely forested environments
      where its elongate wings would have become easily damaged. Instead, the species
      lived in more open habitats and possessed greatly enlarged compound eyes. These
      were dorsally hypertrophied, a specialization for long-distance vision above the
      animal in flight, a trait convergent with modern hawker dragonflies. Sturdy
      mandibles with acute teeth, strong spines on tibiae and tarsi, and a pronounced
      thoracic skewness are identical to those specializations used by dragonflies in
      capturing prey while in flight. The Palaeozoic Odonatoptera thus exhibited
      considerable morphological specializations associated with behaviours
      attributable to 'hawkers' or 'perchers' among extant Odonata.

PMID- 30108285
TI  - A manganese porphyrin-based T1 contrast agent for cellular MR imaging of human
      embryonic stem cells.
AB  - MRI for non-invasive cell tracking is recognized for enabling pre-clinical
      research on stem cell therapy. Yet, adoption of cellular imaging in stem cell
      research has been restricted to sites with experience in MR contrast agent
      synthesis and to small animal models that do not require scaled-up synthesis. In
      this study, we demonstrate the use of a gadolinium-free T1 contrast agent for
      tracking human embryonic stem cells. The agent, MnPNH2, is an easily synthesized
      manganese porphyrin that can be scaled for large cell numbers. MRI was performed
      on a 3 T clinical scanner. Cell pellets labeled at different MnPNH2
      concentrations for 24 hours demonstrated a decrease in T1 relaxation time of
      nearly two-fold (P < 0.05), and cellular contrast was maintained for 24 hours (P
      < 0.05). Cell viability (Trypan blue) and differentiation (embryoid body
      formation) were unaffected. Cell uptake of Mn on inductively coupled plasma
      atomic emission spectroscopy corroborated MRI findings, and fluorescence
      microscopy revealed the agent localized mainly in cell-cell boundaries and cell
      nuclei. Labeled cells transplanted in rats demonstrated the superior sensitivity
      of MnPNH2 for in-vivo cell tracking.

PMID- 30108286
TI  - Micro-CT 3D imaging reveals the internal structure of three abyssal xenophyophore
      species (Protista, Foraminifera) from the eastern equatorial Pacific Ocean.
AB  - Xenophyophores, giant foraminifera, are distinctive members of the deep-sea
      megafauna that accumulate large masses of waste material ('stercomare') within
      their agglutinated tests, and organise their cells as branching strands enclosed
      within an organic tube (the 'granellare' system). Using non-destructive, three
      dimensional micro-CT imaging we explored these structures in three species from
      the abyssal eastern Pacific Clarion-Clipperton Zone (CCZ). In Psammina spp., the
      low-density stercomare occupied much of the test interior, while high-density
      granellare strands branched throughout the structure. In Galatheammina sp. the
      test comprised a mixture of stercomare and test particles, with the granellare
      forming a web-like system of filaments. The granellare occupied 2.8-5.1%, the
      stercomare 72.4-82.4%, and test particles 14.7-22.5%, of the 'body' volume in the
      two Psammina species. The corresponding proportions in Galatheammina sp. were
      1.7% (granellare), 39.5% (stercomare) and 58.8% (test particles). These data
      provide a potential basis for estimating the contribution of xenophyophores to
      seafloor biomass in areas like the CCZ where they dominate the megafauna. As in
      most xenophyophore species, the granellare hosted huge numbers of tiny barite
      crystals. We speculate that these help to support the extensive granellare
      system, as well as reducing the cell volume and lightening the metabolic burden
      required to maintain it.

PMID- 30108288
TI  - Antisense treatment alleviates ALS in animals.

PMID- 30108287
TI  - The establishment of a marine focused biorefinery for bioethanol production using
      seawater and a novel marine yeast strain.
AB  - Current technologies for bioethanol production rely on the use of freshwater for
      preparing the fermentation media and use yeasts of a terrestrial origin. Life
      cycle assessment has suggested that between 1,388 to 9,812 litres of freshwater
      are consumed for every litre of bioethanol produced. Hence, bioethanol is
      considered a product with a high-water footprint. This paper investigated the use
      of seawater-based media and a novel marine yeast strain 'Saccharomyces cerevisiae
      AZ65' to reduce the water footprint of bioethanol. Results revealed that S.
      cerevisiae AZ65 had a significantly higher osmotic tolerance when compared with
      the terrestrial reference strain. Using 15-L bioreactors, S. cerevisiae AZ65
      produced 93.50 g/L ethanol with a yield of 83.33% (of the theoretical yield) and
      a maximum productivity of 2.49 g/L/h when using seawater-YPD media. This approach
      was successfully applied using an industrial fermentation substrate (sugarcane
      molasses). S. cerevisiae AZ65 produced 52.23 g/L ethanol using molasses media
      prepared in seawater with a yield of 73.80% (of the theoretical yield) and a
      maximum productivity of 1.43 g/L/h. These results demonstrated that seawater can
      substitute freshwater for bioethanol production without compromising production
      efficiency. Results also revealed that marine yeast is a potential candidate for
      use in the bioethanol industry especially when using seawater or high salt based
      fermentation media.

PMID- 30108289
TI  - Topographic aspect affects the vegetation restoration and artificial soil quality
      of rock-cut slopes restored by external-soil spray seeding.
AB  - External-soil spray seeding (ESSS), a technique of spraying artificial soil
      materials onto bare slopes for vegetation cover construction, has been widely
      used to restore rock-cut slopes. However, studies on the effect of the practical
      application of this technique on different topographic aspects have been rarely
      performed. In this study, two topographic aspects, namely, north-facing versus
      south-facing, were investigated under two railway lines, and two local natural
      slopes (north-facing versus south-facing) were selected as references. Vegetation
      and soil conditions, which are paramount aspects of ecological restoration
      assessment, were characterized in terms of the richness and diversity indices,
      vegetation canopy cover, basic soil physico-chemical properties, and structural
      characteristics of these slopes. Results showed that (1) the topographic aspect
      significantly affected the vegetation restoration and artificial soil quality of
      rock-cut slopes restored by ESSS; (2) the ecological restoration effect of north
      facing slopes were better than that of south-facing slopes; and (3) the
      vegetation and soil conditions of natural slopes were better than those of rock
      cut slopes. Therefore, additional scientific management measures should be
      implemented to promote the ecological restoration of rock-cut slopes, especially
      for south-facing slopes.

PMID- 30108292
TI  - Persistent inequalities in unplanned hospitalisation among colon cancer patients
      across critical phases of their care pathway, England, 2011-13.
AB  - BACKGROUND: Reducing hospital emergency admissions is a key target for all modern
      health systems. METHODS: We analysed colon cancer patients diagnosed in 2011-13
      in England. We screened their individual Hospital Episode Statistics records in
      the 90 days pre-diagnosis, the 90 days post-diagnosis, and the 90 days pre-death
      (in the year following diagnosis), for the occurrence of hospital emergency
      admissions (HEAs). RESULTS: Between a quarter and two thirds of patients
      experience HEA in the three 90-day periods examined: pre-diagnosis, post
      diagnosis and before death. Patients with tumour stage I-III from more deprived
      backgrounds had higher proportions of HEAs than less deprived patients during all
      studied periods. This remains even after adjusting for differing distributions of
      risk factors such as age, sex, comorbidity and stage at diagnosis. CONCLUSIONS:
      Although in some cases HEAs might be unavoidable or even appropriate, the
      proportion of HEAs varies by socioeconomic status, even after controlling for the
      usual patient factors, suggestive of remediable causes of excess emergency
      healthcare utilisation in patients belonging to higher deprivation groups. Future
      inquiries should address the potential role of clinical complications, sub
      optimal healthcare administration, premature discharge or a lack of social
      support as potential explanations for these patterns of inequality.

PMID- 30108291
TI  - Diagnosing orthostatic hypotension with continuous and interval blood pressure
      measurement devices.
AB  - Orthostatic hypotension (OH) is defined as a drop in systolic blood pressure
      (SBP) of >=20 mm Hg and/or a drop in diastolic blood pressure (DBP) of >=10 mm Hg
      within 3 min of standing. The international guidelines recommend ideally
      diagnosing OH with a continuous blood pressure (BP) measurement device, although
      in daily practice interval BP measurement devices are used more often. We aimed
      to investigate the difference in observed prevalence of OH between an interval
      and a continuous BP measurement device. A total of 104 patients with a mean age
      of 69 years were included. The prevalence of OH was 35.6% (95% CI: 26.4-44.8)
      with the interval BP measurement and 45.2% (95% CI: 35.6-54.8) with the
      continuous BP measurement device (P = .121). Lin's coefficient of concordance
      ranged from 0.47 to 0.59 for the drop in systolic blood pressure and from 0.33 to
      0.42 for the drop in diastolic blood pressure. The positive proportion of
      agreement in diagnosis of OH between the interval and continuous measure was
      59.5% and the negative proportion of agreement was 72.5%. Although the prevalence
      of OH was not significantly different between the continuous and the interval BP
      measurement devices using a similar amount of measurement, the concordance
      between interval and continuous measure is low resulting in low positive and
      negative proportions of agreement in the diagnosis of OH. We conclude that
      continuous BP measurement cannot be substituted by an interval BP measurement to
      diagnose OH.

PMID- 30108293
TI  - The growing importance of radiation worker studies.
AB  - Large radiation worker studies have the potential to provide precise risk
      estimates for protracted exposure to low-level ionising radiation. Recent worker
      studies have reported statistically discernible dose-related increased risks of
      cancer; however, results must be interpreted with care, and occupational
      radiation doses need to be treated with particular attention.

PMID- 30108294
TI  - Cancer mortality and incidence following external occupational radiation
      exposure: an update of the 3rd analysis of the UK national registry for radiation
      workers.
AB  - BACKGROUND: This study provides direct evidence of cancer risk from low dose and
      dose rate occupational external radiation exposures. METHODS: Cancer mortality
      and incidence were studied in relation to external radiation exposure in the
      National Registry for Radiation Workers. A cohort of 167,003 workers followed for
      an average of 32 years was analysed using Poisson regression methods. RESULTS:
      Mortality and incidence risks were significantly raised for the group of all
      malignant neoplasms excluding leukaemia (ERR/Sv mortality = 0.28; 90%CI: 0.06,
      0.53, ERR/Sv incidence = 0.28; 90%CI: 0.10, 0.48) but with narrower confidence
      bounds compared with the previous analysis of this cohort reflecting the
      increased statistical power from the additional 10 years of follow-up
      information. The linear trends in relative risk for both mortality and incidence
      of these cancers remained statistically significantly raised when information
      relating to cumulative doses above 100 mSv was excluded (ERR/Sv mortality = 1.42;
      90%CI: 0.51, 2.38 and ERR/Sv incidence = 1.18; 90%CI: 0.47, 1.92). CONCLUSIONS:
      This study improved the precision of the cancer risk estimates seen in the third
      analysis of the NRRW cohort. The overall results remain consistent with the risk
      estimates from the Life Span Study and those adopted in the current ICRP
      recommendations.

PMID- 30108295
TI  - Plant diversity drives global patterns of insect invasions.
AB  - During the last two centuries, thousands of insect species have been transported
      (largely inadvertently) and established outside of their native ranges worldwide,
      some with catastrophic ecological and economic impacts. Global variation in
      numbers of invading species depends on geographic variation in propagule pressure
      and heterogeneity of environmental resistance to invasions. Elton's diversity
      invasibility hypothesis, proposed over sixty years ago, has been widely explored
      for plants but little is known on how biodiversity affects insect invasions. Here
      we use species inventories from 44 land areas, ranging from small oceanic islands
      to entire continents in various world regions, to show that numbers of
      established insect species are primarily driven by diversity of plants, with both
      native and non-native plant species richness being the strongest predictor of
      insect invasions. We find that at large spatial scales, plant diversity directly
      explains variation in non-native insect species richness among world regions,
      while geographic factors such as land area, climate and insularity largely affect
      insect invasions indirectly via their effects on local plant richness.

PMID- 30108296
TI  - The induction of the fibroblast extracellular senescence metabolome is a dynamic
      process.
AB  - Cellular senescence is often associated with irreparable DNA double strand breaks
      (IrrDSBs) which accumulate with chronological age (IrrDSBsen). The removal of
      senescent cells ameliorates several age-related diseases in mice but the
      translation of these findings into a clinical setting would be aided by the
      characterisation of non-invasive biomarkers of senescent cells. Several serum
      metabolites are independent indicators of chronological age and some of these
      accumulate outside senescent fibroblasts independently of cell cycle arrest,
      repairable DNA breaks and cell size (the extracellular senescence metabolome, or
      ESM). The post-mitotic phase of senescence is dynamic, making the detection of
      senescent cells in vivo difficult. An unbiased metabolomic screen of the
      IrrDSBsen fibroblast ESM also showed differences in the times of initiation and
      maintenance of different metabolites but generally the ESM altered progressively
      over the 20 day study period unlike the reported transcriptional profiles. This
      more detailed analysis of IrrDSBsen identified several new ESM metabolites that
      are associated with chronological ageing. Targeted analysis of citrate confirmed
      the dynamic nature of this metabolite in two cell lines and revealed its
      independence from the senescence effector p16INK4A. These data will aid our
      understanding of metabolic signatures of ageing and their relationship to
      cellular senescence and IrrDSBs.

PMID- 30108298
TI  - Publisher Correction: The SERK3 elongated allele defines a role for BIR
      ectodomains in brassinosteroid signalling.
AB  - In the version of this Letter originally published, there were errors in the x
      axis labels of Figs 1, 2 and 4: in Fig. 1b, the label Col-0 should not have been
      included on the axis; in Fig. 2b BIR should have read BIR2, and DN221 should have
      read D122N; in Fig. 4f, pSEK3 should have read pSERK3. These figures have now
      been amended in all versions of the Letter.

PMID- 30108297
TI  - Publisher Correction: Core microbiomes for sustainable agroecosystems.
AB  - Owing to a technical error, this Perspective was originally published without its
      received and accepted dates; the dates "Received: 31 December 2017; Accepted: 23
      March 2018" have now been included in all versions.

PMID- 30108300
TI  - Can neocortical feedback alter the sign of plasticity?

PMID- 30108290
TI  - Skeletal muscle mitochondrial remodeling in exercise and diseases.
AB  - Skeletal muscle fitness and plasticity is an important determinant of human
      health and disease. Mitochondria are essential for maintaining skeletal muscle
      energy homeostasis by adaptive re-programming to meet the demands imposed by a
      myriad of physiologic or pathophysiological stresses. Skeletal muscle
      mitochondrial dysfunction has been implicated in the pathogenesis of many
      diseases, including muscular dystrophy, atrophy, type 2 diabetes, and aging
      related sarcopenia. Notably, exercise counteracts the effects of many chronic
      diseases on skeletal muscle mitochondrial function. Recent studies have revealed
      a finely tuned regulatory network that orchestrates skeletal muscle mitochondrial
      biogenesis and function in response to exercise and in disease states. In
      addition, increasing evidence suggests that mitochondria also serve to
      "communicate" with the nucleus and mediate adaptive genomic re-programming. Here
      we review the current state of knowledge relevant to the dynamic remodeling of
      skeletal muscle mitochondria in response to exercise and in disease states.

PMID- 30108301
TI  - Reply to 'Can neocortical feedback alter the sign of plasticity?'

PMID- 30108299
TI  - Role of the Macrophage Migration Inhibitory Factor (MIF) in the survival of first
      trimester human placenta under induced stress conditions.
AB  - Macrophage Migration Inhibitory Factor (MIF) is a multifunctional molecule highly
      secreted by human placenta mainly in the early phases of pregnancy. Studies in
      different cells show that MIF is a pro-survival factor by binding to its receptor
      CD74. By using the in vitro model of placental explants from first trimester
      pregnancy, we investigated the role of MIF in the survival of placental cells
      under induced stress conditions that promote apoptosis or mimic the hypoxia/re
      oxygenation (H/R) injury that placenta could suffer in vivo. We demonstrated that
      recombinant MIF (rMIF) treatment was able to reduce caspase-3 activation when
      cultures were challenged with the apoptosis-inducer Carbonyl cyanide 4
      (trifluoromethoxy)phenylhydrazone (FCCP) while, in the cultures exposed to H/R,
      the treatment with rMIF did not show any effect. However, a significant increase
      in caspase-3 and caspase-8 activation was found when H/R-exposed cultures, were
      treated with anti-MIF or anti-CD74 antibody. We also observed that under H/R, a
      significant amount of endogenous MIF was released into the medium, which could
      account for the lack of effect of rMIF added to the cultures. Our results
      demonstrate for the first time that the MIF/CD74 axis contributes to maintain
      trophoblast homeostasis, by preventing abnormal apoptotic death.

PMID- 30108302
TI  - Impact on predictability of tropical and mid-latitude cyclones by extra Arctic
      observations.
AB  - Recent research has demonstrated that additional winter radiosonde observations
      in Arctic regions enhance the predictability of mid-latitude weather extremes by
      reducing uncertainty in the flow of localised tropopause polar vortices. The
      impacts of additional Arctic observations during summer are usually confined to
      high latitudes and they are difficult to realize at mid-latitudes because of the
      limited scale of localised tropopause polar vortices. However, in certain
      climatic states, the jet stream can intrude remarkably into the mid-latitudes,
      even in summer; thus, additional Arctic observations might improve analysis
      validity and forecast skill for summer atmospheric circulations over the Northern
      Hemisphere. This study examined such cases that occurred in 2016 by focusing on
      the prediction of the intensity and track of tropical cyclones (TCs) over the
      North Atlantic and North Pacific, because TCs are representative of extreme
      weather in summer. The predictabilities of three TCs were found influenced by
      additional Arctic observations. Comparisons with ensemble reanalysis data
      revealed that large errors propagate from the data-sparse Arctic into the mid
      latitudes, together with high-potential-vorticity air. Ensemble forecast
      experiments with different reanalysis data confirmed that additional Arctic
      observations sometimes improve the initial conditions of upper-level troposphere
      circulations.

PMID- 30108304
TI  - The cost of toxin production in phytoplankton: the case of PST producing
      dinoflagellates.
AB  - Many species of phytoplankton produce toxins that may provide protection from
      grazing. In that case one would expect toxin production to be costly; else all
      species would evolve toxicity. However, experiments have consistently failed to
      show any costs. Here, we show that costs of toxin production are environment
      dependent but can be high. We develop a fitness optimization model to estimate
      rate, costs, and benefits of toxin production, using PST (paralytic shellfish
      toxin) producing dinoflagellates as an example. Costs include energy and material
      (nitrogen) costs estimated from well-established biochemistry of PSTs, and
      benefits are estimated from relationship between toxin content and grazing
      mortality. The model reproduces all known features of PST production:
      inducibility in the presence of grazer cues, low toxicity of nitrogen-starved
      cells, but high toxicity of P-limited and light-limited cells. The model predicts
      negligible reduction in cell division rate in nitrogen replete cells, consistent
      with observations, but >20% reduction when nitrogen is limiting and abundance of
      grazers high. Such situation is characteristic of coastal and oceanic waters
      during summer when blooms of toxic algae typically develop. The investment in
      defense is warranted, since the net growth rate is always higher in defended than
      in undefended cells.

PMID- 30108305
TI  - Terrestriality and bacterial transfer: a comparative study of gut microbiomes in
      sympatric Malagasy mammals.
AB  - The gut microbiomes of mammals appear to mirror their hosts' phylogeny,
      suggesting host-driven microbial community assembly. Yet, much of this evidence
      stems from comparative studies of distinct wild or captive populations that lack
      data for disentangling the relative influences of shared phylogeny and
      environment. Here, we present phylogenetic and multivariate analyses of gut
      microbiomes from six sympatric (i.e., co-occurring) mammal species inhabiting a 1
      km2 area in western Madagascar-three lemur and three non-primate species-that
      consider genetic, dietary, and ecological predictors of microbiome functionality
      and composition. Host evolutionary history, indeed, appears to shape gut
      microbial patterns among both closely and distantly related species. However, we
      also find that diet-reliance on leaves versus fruit-is the best predictor of
      microbiome similarity among closely related lemur species, and that host
      substrate use-ground versus tree-constrains horizontal transmission via
      incidental contact with feces, with arboreal species harboring far more distinct
      communities than those of their terrestrial and semi-terrestrial counterparts.

PMID- 30108303
TI  - Following the terrestrial tracks of Caulobacter - redefining the ecology of a
      reputed aquatic oligotroph.
AB  - For the past 60 years Caulobacter spp. have been commonly attributed an aquatic
      and oligotrophic lifestyle yet are not uncommon in nutrient-rich or soil
      environments. This study evaluates the environmental and ecological associations
      of Caulobacter to reconcile past evidence, largely limited to culturing and
      microscopy, with currently available metagenomic and genomic data. The
      distribution of Caulobacter species and their characteristic adhesion-conferring
      genes, holdfast (hfaAB), were determined using collections of 10,641 16S rRNA
      gene libraries (196 studies) and 2625 shotgun metagenomes (190 studies) from a
      range of terrestrial and aquatic environments. Evidence for ecotypic variation
      was tested in 26 genomes sourced from soil, rhizosphere, plant, groundwater, and
      water. Caulobacter were, on average, fourfold more relatively abundant in soil
      than in aquatic environments, and abundant in decomposing wood, compost, and
      particulate matter (in air and water). Caulobacter holdfast genes were 35-fold
      more abundant in soils than aquatic environments. Ecotypic differences between
      soil and aquatic Caulobacter were evident in the environmental associations of
      several species and differences in genome size and content among isolates.
      However, most abundant species were common to both environments, suggesting
      populations exist in a continuum that was evident in the re-analysis of studies
      on the temporal dynamics of, and sources of bacterioplankton to, lakes and
      rivers. This study provides a new perspective on the ecological profile of
      Caulobacter, demonstrating that members of this genus are predominantly soil
      borne, possess an overlooked role in plant matter decomposition and a dependency
      on water-mediated dispersal.

PMID- 30108306
TI  - Elucidation of glutamine lipid biosynthesis in marine bacteria reveals its
      importance under phosphorus deplete growth in Rhodobacteraceae.
AB  - Marine microorganisms employ multiple strategies to cope with transient and
      persistent nutrient limitation, one of which, for alleviating phosphorus (P)
      stress, is to substitute membrane glycerophospholipids with non-P containing
      surrogate lipids. Such a membrane lipid remodelling strategy enables the most
      abundant marine phytoplankton and heterotrophic bacteria to adapt successfully to
      nutrient scarcity in marine surface waters. An important group of non-P lipids,
      the aminolipids which lack a diacylglycerol backbone, are poorly studied in
      marine microbes. Here, using a combination of genetic, lipidomics and
      metagenomics approaches, we reveal for the first time the genes (glsB, olsA)
      required for the formation of the glutamine-containing aminolipid. Construction
      of a knockout mutant in either glsB or olsA in the model marine bacterium
      Ruegeria pomeroyi DSS-3 completely abolished glutamine lipid production.
      Moreover, both mutants showed a considerable growth cost under P-deplete
      conditions and the olsA mutant, that is unable to produce the glutamine and
      ornithine aminolipids, ceased to grow under P-deplete conditions. Analysis of
      sequenced microbial genomes show that glsB is primarily confined to the
      Rhodobacteraceae family, which includes the ecologically important marine
      Roseobacter clade that are key players in the marine sulphur and nitrogen cycles.
      Analysis of the genes involved in glutamine lipid biosynthesis in the Tara ocean
      metagenome dataset revealed the global occurrence of glsB in marine surface
      waters and a positive correlation between glsB abundance and N* (a measure of the
      deviation from the canonical Redfield ratio), suggesting glutamine lipid plays an
      important role in the adaptation of marine Rhodobacteraceae to P limitation.

PMID- 30108307
TI  - A rock physics modelling algorithm for simulating the elastic parameters of shale
      using well logging data.
AB  - As a high-resolution geophysical method employed by the oil and gas industry,
      well logging can be used to accurately investigate reservoirs. Challenges
      associated with shale gas reservoir exploration increase the importance of
      applying elastic parameters or velocity at the logging scale. An efficient shale
      rock physics model is the foundation for the successful application of this
      method. We propose a procedure for modelling shale rock physics in which an
      appropriate modelling method is applied for different compositions of shale rock.
      The stiffnesses of the kerogen and fluid (oil, gas or water) mixture are obtained
      with the Kuster-Toksoz model, which assumes that the fluid is included in the
      kerogen matrix. A self-consistent approximation method is used to model clay,
      where the clay pores are filled with formation water. The Backus averaging model
      is then used to simulate the influence of laminated clay and laminated kerogen.
      Elastic parameter simulations using well logging data show the importance of
      treating the volume fractions of laminated clay and kerogen carefully. A
      comparison of the measured compressional slowness and modelled compressional
      slowness shows the efficiency of the proposed modelling procedure.

PMID- 30108308
TI  - Avalanche precursors of failure in hierarchical fuse networks.
AB  - We study precursors of failure in hierarchical random fuse network models which
      can be considered as idealizations of hierarchical (bio)materials where fibrous
      assemblies are held together by multi-level (hierarchical) cross-links. When such
      structures are loaded towards failure, the patterns of precursory avalanche
      activity exhibit generic scale invariance: irrespective of load, precursor
      activity is characterized by power-law avalanche size distributions without
      apparent cut-off, with power-law exponents that decrease continuously with
      increasing load. This failure behavior and the ensuing super-rough crack
      morphology differ significantly from the findings in non-hierarchical structures.

PMID- 30108310
TI  - TiOxNy Modified TiO2 Powders Prepared by Plasma Enhanced Atomic Layer Deposition
      for Highly Visible Light Photocatalysis.
AB  - In this work, TiN film deposited by plasma enhanced atomic layer deposition
      (PEALD) is adopted to modify the commercial anatase TiO2 powders. A series of
      analyses indicate that the surface modification of 20, 50 and 100 cycles of TiN
      by PEALD does not change the morphology, crystal size, lattice parameters, and
      surface area of TiO2 nano powders, but forms an ultrathin amorphous layer of
      nitrogen doped TiO2 (TiOxNy) on the powder surfaces. This ultrathin TiOxNy can
      facilitate the absorption of TiO2 in visible light spectrum. As a result, TiOxNy
      coated TiO2 powders exhibit excellent photocatalytic degradation towards methyl
      orange under the visible light with good photocatalytic stability compared to
      pristine TiO2 powders. TiOxNy (100 cycles PEALD TiN) coated TiO2 powders exhibit
      the excellent photocatalytic activity with the degradation efficiency of 96.5% in
      2 hours, much higher than that of pristine TiO2 powder of only 4.4%. These
      results clearly demonstrate that only an ultrathin surface modification layer can
      dramatically improve the visible light photocatalytic activity of commercial TiO2
      powders. Therefore, this surface modification using ALD is an extremely promising
      route to prepare visible light active photocatalysts.

PMID- 30108309
TI  - Sensitivity of Colorectal Cancer to Arginine Deprivation Therapy is Shaped by
      Differential Expression of Urea Cycle Enzymes.
AB  - Tumors deficient in the urea cycle enzymes argininosuccinate synthase-1 (ASS1)
      and ornithine transcarbamylase (OTC) are unable to synthesize arginine and can be
      targeted using arginine-deprivation therapy. Here, we show that colorectal
      cancers (CRCs) display negligible expression of OTC and, in subset of cases, ASS1
      proteins. CRC cells fail to grow in arginine-free medium and dietary arginine
      deprivation slows growth of cancer cells implanted into immunocompromised mice.
      Moreover, we report that clinically-formulated arginine-degrading enzymes are
      effective anticancer drugs in CRC. Pegylated arginine deiminase (ADI-PEG20),
      which degrades arginine to citrulline and ammonia, affects growth of ASS1
      negative cells, whereas recombinant human arginase-1 (rhArg1peg5000), which
      degrades arginine into urea and ornithine, is effective against a broad spectrum
      of OTC-negative CRC cell lines. This reflects the inability of CRC cells to
      recycle citrulline and ornithine into the urea cycle. Finally, we show that
      arginase antagonizes chemotherapeutic drugs oxaliplatin and 5-fluorouracil (5
      FU), whereas ADI-PEG20 synergizes with oxaliplatin in ASS1-negative cell lines
      and appears to interact with 5-fluorouracil independently of ASS1 status.
      Overall, we conclude that CRC is amenable to arginine-deprivation therapy, but we
      warrant caution when combining arginine deprivation with standard chemotherapy.

PMID- 30108312
TI  - Differential effects of Foxp2 disruption in distinct motor circuits.
AB  - Disruptions of the FOXP2 gene cause a speech and language disorder involving
      difficulties in sequencing orofacial movements. FOXP2 is expressed in cortico
      striatal and cortico-cerebellar circuits important for fine motor skills, and
      affected individuals show abnormalities in these brain regions. We selectively
      disrupted Foxp2 in the cerebellar Purkinje cells, striatum or cortex of mice and
      assessed the effects on skilled motor behaviour using an operant lever-pressing
      task. Foxp2 loss in each region impacted behaviour differently, with striatal and
      Purkinje cell disruptions affecting the variability and the speed of lever-press
      sequences, respectively. Mice lacking Foxp2 in Purkinje cells showed a prominent
      phenotype involving slowed lever pressing as well as deficits in skilled
      locomotion. In vivo recordings from Purkinje cells uncovered an increased simple
      spike firing rate and decreased modulation of firing during limb movements. This
      was caused by increased intrinsic excitability rather than changes in excitatory
      or inhibitory inputs. Our findings show that Foxp2 can modulate different aspects
      of motor behaviour in distinct brain regions, and uncover an unknown role for
      Foxp2 in the modulation of Purkinje cell activity that severely impacts skilled
      movements.

PMID- 30108314
TI  - Panic results in unique molecular and network changes in the amygdala that
      facilitate fear responses.
AB  - Recurrent panic attacks (PAs) are a common feature of panic disorder (PD) and
      post-traumatic stress disorder (PTSD). Several distinct brain regions are
      involved in the regulation of panic responses, such as perifornical hypothalamus
      (PeF), periaqueductal gray, amygdala and frontal cortex. We have previously shown
      that inhibition of GABA synthesis in the PeF produces panic-vulnerable rats.
      Here, we investigate the mechanisms by which a panic-vulnerable state could lead
      to persistent fear. We first show that optogenetic activation of glutamatergic
      terminals from the PeF to the basolateral amygdala (BLA) enhanced the
      acquisition, delayed the extinction and induced the persistence of fear responses
      3 weeks later, confirming a functional PeF-amygdala pathway involved in fear
      learning. Similar to optogenetic activation of PeF, panic-prone rats also
      exhibited delayed extinction. Next, we demonstrate that panic-prone rats had
      altered inhibitory and enhanced excitatory synaptic transmission of the principal
      neurons, and reduced protein levels of metabotropic glutamate type 2 receptor
      (mGluR2) in the BLA. Application of an mGluR2-positive allosteric modulator (PAM)
      reduced glutamate neurotransmission in the BLA slices from panic-prone rats.
      Treating panic-prone rats with mGluR2 PAM blocked sodium lactate (NaLac)-induced
      panic responses and normalized fear extinction deficits. Finally, in a subset of
      patients with comorbid PD, treatment with mGluR2 PAM resulted in complete
      remission of panic symptoms. These data demonstrate that a panic-prone state
      leads to specific reduction in mGluR2 function within the amygdala network and
      facilitates fear, and mGluR2 PAMs could be a targeted treatment for panic
      symptoms in PD and PTSD patients.

PMID- 30108315
TI  - Cell encapsulation enhances antidepressant effect of the mesenchymal stem cells
      and counteracts depressive-like behavior of treatment-resistant depressed rats.
AB  - Despite the advances in pharmacological therapies, only the half of depressed
      patients respond to currently available treatment. Thus, the need for further
      investigation and development of effective therapies, especially those designed
      for treatment-resistant depression, has been sorely needed. Although
      antidepressant effects of mesenchymal stem cells (MSCs) have been reported, the
      potential benefit of this cell therapy on treatment-resistant depression is
      unknown. Cell encapsulation may enhance the survival rate of grafted cells, but
      the therapeutic effects and mechanisms mediating encapsulation of MSCs remain
      unexplored. Here, we showed that encapsulation enhanced the antidepressant
      effects of MSCs by attenuating depressive-like behavior of Wistar Kyoto (WKY)
      rats, which are considered as a promising animal model of treatment-resistant
      depression. The implantation of encapsulated MSCs (eMSCs) into the lateral
      ventricle counteracted depressive-like behavior and enhanced the endogenous
      neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of the
      hippocampus, whereas the implantation of MSCs without encapsulation or the
      implantation of eMSCs into the striatum did not show such ameliorative effects.
      eMSCs displayed robust and stable secretion of vascular endothelial growth factor
      (VEGF), brain-derived neurotrophic factor, fibroblast growth factor-2, and
      ciliary neurotrophic factor (CNTF), and the implantation of eMSCs into the
      lateral ventricle activated relevant pathways associated with these growth
      factors. Additionally, eMSCs upregulated intrinsic expression of VEGF and CNTF
      and their receptors. This study suggests that the implantation of eMSCs into the
      lateral ventricle exerted antidepressant effects likely acting via neurogenic
      pathways, supporting their utility for depression treatment.

PMID- 30108313
TI  - Distinct brain structure and behavior related to ADHD and conduct disorder
      traits.
AB  - Attention-Deficit/Hyperactivity Disorder (ADHD) and conduct disorder (CD)
      exemplify top-down dysregulation conditions that show a large comorbidity and
      shared genetics. At the same time, they entail two different types of
      symptomology involving mainly non-emotional or emotional dysregulation. Few
      studies have tried to separate the specific biology underlying these two
      dimensions. It has also been suggested that both types of conditions consist of
      extreme cases in the general population where the symptoms are widely
      distributed. Here we test whether brain structure is specifically associated to
      ADHD or CD symptoms in a general population of adolescents (n = 1093) being part
      of the IMAGEN project. Both ADHD symptoms and CD symptoms were related to similar
      and overlapping MRI findings of a smaller structure in prefrontal and anterior
      cingulate cortex. However, our regions of interest (ROI) approach indicated that
      gray matter volume (GMV) and surface area (SA) in dorsolateral/dorsomedial
      prefrontal cortex and caudal anterior cingulate cortex were negatively associated
      to ADHD symptoms when controlling for CD symptoms while rostral anterior
      cingulate cortex GMV was negatively associated to CD symptoms when controlling
      for ADHD symptoms. The structural findings were mirrored in performance of
      neuropsychological tests dependent on prefrontal and anterior cingulate regions,
      showing that while performance on the Stop Signal test was specifically related
      to the ADHD trait, delayed discounting and working memory were related to both
      ADHD and CD traits. These results point towards a partially domain specific and
      dimensional capacity in different top-down regulatory systems associated with
      ADHD and CD symptoms.

PMID- 30108311
TI  - Whole exome sequencing study identifies novel rare and common Alzheimer's
      Associated variants involved in immune response and transcriptional regulation.
AB  - The Alzheimer's Disease Sequencing Project (ADSP) undertook whole exome
      sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively
      normal controls primarily of European ancestry (EA), among whom 218 cases and 177
      controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score
      and family history were used to select cases most likely to harbor novel AD risk
      variants and controls least likely to develop AD by age 85 years. We tested ~1.5
      million single nucleotide variants (SNVs) and 50,000 insertion-deletion
      polymorphisms (indels) for association to AD, using multiple models considering
      individual variants as well as gene-based tests aggregating rare, predicted
      functional, and loss of function variants. Sixteen single variants and 19 genes
      that met criteria for significant or suggestive associations after multiple
      testing correction were evaluated for replication in four independent samples;
      three with whole exome sequencing (2,778 cases, 7,262 controls) and one with
      genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343
      cases, 11,527 controls). The top findings in the discovery sample were also
      followed-up in the ADSP whole-genome sequenced family-based dataset (197 members
      of 42 EA families and 501 members of 157 CH families). We identified novel and
      predicted functional genetic variants in genes previously associated with AD. We
      also detected associations in three novel genes: IGHG3 (p = 9.8 * 10-7), an
      immunoglobulin gene whose antibodies interact with beta-amyloid, a long non
      coding RNA AC099552.4 (p = 1.2 * 10-7), and a zinc-finger protein ZNF655 (gene
      based p = 5.0 * 10-6). The latter two suggest an important role for
      transcriptional regulation in AD pathogenesis.

PMID- 30108318
TI  - Natural regulatory plasma cells.

PMID- 30108316
TI  - Immunoproteomic Identification and Characterization of Leishmania Membrane
      Proteins as Non-Invasive Diagnostic Candidates for Clinical Visceral
      Leishmaniasis.
AB  - Visceral leishmaniasis (VL), a potentially fatal disease is an outcome of
      infection caused by the parasite Leishmania donovani. The clinical diagnostic
      tests for this disease are still related to invasive tissue aspiration or
      serological immunochromatography. Advancements in immunoproteomics such as two
      dimensional gel electrophoresis, mass spectrometry, B cell epitope prediction,
      and peptide synthesis have enabled researchers to discover newer biomarkers for
      disease diagnosis. In this study, we have screened several urine-reactive
      leishmanial membrane proteins as potential biomarker candidates. In the
      immunoblot assay, three proteins 51, 55 and 63 kDa showed 100% reactivity to the
      urine of 47 VL patients and nonreactive to 18 healthy and other diseases. Mass
      spectrometry revealed the identity of 51, 55 and 63 kDa proteins as elongation
      factor 1alpha (EF1-alpha), alpha-tubulin, and glycoprotein 63, respectively. B
      cell reactive epitopes of these proteins were mapped through bioinformatic tools
      and one epitope from each protein that had the highest score were synthesized.
      All the three native electroeluted proteins and their corresponding synthetic
      peptides were tested through ELISA for reactivity with VL and control urine
      samples. While all three demonstrated good reactivity, the diagnostic performance
      of EF1-alpha was the best. Our findings illustrate the use of urine-based
      proteomic approach for biomarker discovery in non-invasive clinical diagnosis of
      VL.

PMID- 30108317
TI  - Lily Pollen Tubes Pulse According to a Simple Spatial Oscillator.
AB  - Polar growth is a fundamental mode of cell morphogenesis observed in nearly all
      major groups of organisms. Among polarly growing cells, the angiosperm pollen
      tubes have emerged as powerful experimental systems in large part because of
      their oscillatory growth, which provides a window into the network of
      interactions regulating morphogenesis. Empirical studies of oscillatory pollen
      tubes have sought to uncover the temporal sequence of cellular and molecular
      events that constitutes an oscillatory cycle. Here we show that in lily pollen
      tubes the distance or wavelength (lambda = 6.3 +/- 1.7 MUm) over which an
      oscillatory cycle unfolds is more robust than the period of oscillation (tau =
      39.1 +/- 17.6 s) (n = 159 cells). Moreover, the oscillatory cycle is divided into
      slow and fast phases, with each phase unfolding over precisely one half of the
      wavelength. Using these observations, we show that a simple spatial bi-oscillator
      predicts the most common modes of oscillation observed in pollen tubes. These
      results call into question the traditional view of pollen tube morphogenesis as a
      temporal succession of cellular events. Space, not time, may be the most natural
      metric to inteprete the morphogenetic dynamics of these cells.

PMID- 30108319
TI  - Familial total anomalous pulmonary venous return with 15q11.2 (BP1-BP2)
      microdeletion.
AB  - A 15q11.2 microdeletion (BP1-BP2) is associated with congenital heart diseases
      (CHDs), developmental delay, and epilepsy. This deletion co-occurs with CHD in 20
      30% patients, but a familial case of CHD and a 15q11.2 deletion has not been
      identified. Here we report the first familial (three siblings) case of total
      anomalous pulmonary venous return associated with 15q11.2 deletion. Array
      comparative genomic hybridization identified a ~395 kb deletion at 15q11.2 in
      patient 1. This deletion was confirmed by fluorescence in situ hybridization in
      patients 1 and 3 and their asymptomatic father. No deleterious mutation was
      identified by proband-only exome sequencing of patient 1. One healthy sibling and
      their mother did not carry the deletion. This deletion is often inherited from
      asymptomatic parents with an estimated low penetrance of 10.4%. Conversely, we
      observed high penetrance of this deletion, but secondary copy-number variants or
      pathogenic variants were not detected in this family.

PMID- 30108320
TI  - Japanese beetles' feeding on milkweed flowers may compromise efforts to restore
      monarch butterfly habitat.
AB  - The eastern North American migratory population of monarch butterflies (Danaus
      plexippus) is in serious decline. Habitat restoration, including adding millions
      of host plants to compensate for loss of milkweed in US cropland, is a key part
      of the international conservation strategy to return this iconic butterfly to
      sustainable status. We report here that Popillia japonica, a polyphagous,
      invasive beetle, aggregates and feeds on flowers of Asclepias syriaca, the
      monarch's most important larval food plant, reducing fruiting and seed set by
      >90% and extensively damaging milkweed umbels in the field. The beetle's ongoing
      incursion into the monarch's key breeding grounds in the US Midwest is likely to
      limit pollination and outcrossing of wild and planted milkweeds, reducing their
      capacity to colonize new areas via seeds. Popillia japonica represents a
      previously undocumented threat to milkweeds that should be considered in models
      for monarch habitat restoration.

PMID- 30108322
TI  - Maximal concentration of intravenous busulfan as a determinant of veno-occlusive
      disease: a pharmacokinetic-pharmacodynamic analysis in 293 hematopoietic stem
      cell transplanted children.
AB  - Veno-occlusive disease (VOD) is a severe adverse reaction to busulfan-containing
      regimens used in the preparation of children for hematopoietic stem cell
      transplantation (HSCT). We conducted a retrospective analysis of data to examine
      determinants of VOD in children who received IV busulfan for HSCT conditioning.
      Busulfan PK parameters as well as various indices (maximal concentration-Cmax,
      area under the concentration-time curve-AUC) were estimated using a validated
      Bayesian approach. The influence of available PK, demographic, and clinical
      variables on the incidence of VOD was evaluated by using logistic regression and
      classification and regression tree (CART) analyses. Among the 293 patients
      included, the mean age was 6.5 years and the mean actual body weight was 26.3 kg.
      The incidence of VOD was 25.6%. Busulfan Cmax as well as weight <9 kg or age <3
      years were identified as independent predictors of VOD in logistic regression
      analysis. CART analysis identified busulfan Cmax over the entire regimen as the
      strongest predictor of VOD. This study suggests that busulfan-associated VOD is
      in part a concentration-dependent reaction. In addition, the youngest children
      showed the highest risk of VOD. These findings may have important implications
      for busulfan dosing and therapeutic drug monitoring practice in HSCT children.

PMID- 30108321
TI  - Characterizing pearls structures using X-ray phase-contrast and neutron imaging:
      a pilot study.
AB  - Some cultured and natural pearls can be reliably distinguished by visual
      inspection and by the use of lens and microscope. However, assessing the origin
      of the pearls could be not straightforward since many different production
      techniques can now be found in the pearl market, for example in salt or
      freshwater environments, with or without a rigid nucleus. This wide range of
      products requires the use of new effective scientific techniques. Indeed, X-ray
      radiography has been used by gemologists since last century as the only safe and
      non-destructive way to visually inspect the interior of a pearl, and recently,
      also X-ray computed micro-tomography was used to better visualize the inner parts
      of the gems. In this study we analyzed samples of natural and cultured pearls by
      means of two non-destructive techniques: the X-ray Phase-Contrast Imaging (PCI)
      and the Neutron Imaging (NI). PCI and NI results will be combined for the first
      time, to better visualize the pearls internal morphology, thus giving relevant
      indications on the pearl formation process.

PMID- 30108324
TI  - Derek Nigel John Hart (1952-2017).

PMID- 30108325
TI  - Cryopreserved versus non-cryopreserved peripheral blood stem cells for autologous
      transplantation after high-dose Melphalan in multiple myeloma: comparative
      analysis.

PMID- 30108323
TI  - High mortality in hematopoietic stem cell transplant-associated thrombotic
      microangiopathy with and without concomitant acute graft-versus-host disease.
AB  - Transplant-associated thrombotic microangiopathy (TA-TMA) remains a major
      complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT).
      We hypothesized that TA-TMA correlates with steroid-refractory acute graft-vs.
      host disease (aGvHD) and assessed 660 patients suffering from either AML n = 248,
      ALL n = 79, CML n = 23, CLL n = 36, lymphoma/myeloma n = 127, MDS/MPN n = 124 or
      bone marrow failure n = 22, who met the study inclusion criteria and had
      undergone myeloablative (78%) and non-myeloablative (22%) allo-HSCT between 2006
      and 2016. Sixty-five (9.8%) of these patients matched the established diagnostic
      criteria for TA-TMA, and TA-TMA was shown to be a relevant independent risk
      factor for mortality (RR 3.27; 95% CI 2.07-5.16). Patients with TA-TMA and
      concomitant aGvHD had a markedly reduced OS compared to patients with TA-TMA or
      aGvHD alone (median 5.6 months vs. 7.6 months vs. 55.4 months, respectively; p <
      0.0001). Risk factors for development of TA-TMA were aGvHD >= grade 2, higher
      aGvHD grade, steroid-refractory aGvHD, CMV reactivation/end-organ disease, but
      not the conditioning regimen (RIC or MAC), usage of TBI or TBI dose, underlying
      disease, donor type, age or sex. TA-TMA, with or without concomitant aGvHD, is a
      significant complication after allo-HSCT and a high-risk factor for a poor
      survival outcome. Thus, allo-HSCT recipients with grade 2-4 aGvHD or CMV viremia
      should be closely monitored for the presence of TA-TMA.

PMID- 30108326
TI  - Anti-thymocyte globulin's activity against acute myeloid leukemia stem cells.
AB  - Rabbit anti-thymocyte globulin (ATG (Thymoglobulin)) kills T cells in vitro and
      probably also in vivo as it prevents graft-vs-host disease (GvHD) in patients.
      Recently we demonstrated that ATG at a clinically relevant concentration (10-50
      mg/L) kills in vitro not only T cells but also leukemic blasts. In the present
      study, we investigated whether ATG kills not only leukemic blasts but also
      leukemic stem cells (LSCs). We used a flow cytometric assay of complement
      mediated cytotoxicity (CDC). ATG-induced death of acute myeloid leukemia (AML)
      cells from patients newly diagnosed with AML was measured among blasts as well as
      LSCs. At 10 mg/L ATG, blasts but not LSCs were killed. At 50 mg/L ATG, both
      blasts and LSCs were killed. We also measured ATG-mediated killing of healthy
      individuals' hematopoietic stem cells (HSCs). Median 2% HSCs from blood and 15%
      HSCs from filgrastim-mobilized grafts were killed with 50 mg/L ATG, compared to
      30% LSCs from the blood of AML patients (p = 0.001 and 0.022, respectively). In
      conclusion, LSCs are sensitive to ATG, however, only at a relatively high ATG
      concentration. At that concentration, LSCs are killed to a higher degree than
      HSCs.

PMID- 30108327
TI  - Audits of collection and apheresis centers: guidelines by the World Marrow Donor
      Association Working Group Quality and Regulation.
AB  - According to the Standards of the World Marrow Donor Association (WMDA),
      unrelated stem cell donor registries and donor centers are responsible for
      compliance of their collection and apheresis centers with these Standards. To
      ensure high stem cell product quality and high standards for safety and
      satisfaction of voluntary unrelated stem cell donors, we here present guidelines
      for audits of collection and apheresis centers that can be used by new and
      established donor registries, as well as by collection centers in preparation of
      audits. We define the general requirements and recommendations for collaboration
      with the collection and apheresis centers and define critical procedures for the
      collection of the stem cell product, such as information session, medical
      assessment, product collection, quality controls, product handover for
      transportation, and donor follow-up. The specific guidelines are accompanied by
      detailed checklists and forms that can be found in Supplementary Information and
      may be used during an initial or follow-up on-site or paper-based audit.

PMID- 30108328
TI  - Retrospective analysis on transient recurrence of steroid-sensitive acute graft
      versus-host disease.

PMID- 30108329
TI  - Baseline calprotectin fails to predict incidence of acute gastrointestinal graft
      vs. host disease: a prospective study.

PMID- 30108330
TI  - Patients with acute myeloid leukemia undergoing allogeneic hematopoietic cell
      transplantation: trends in survival during the past two decades.
AB  - It remains unclear how specific innovations in allogeneic hematopoietic cell
      transplantation (HCT) attained over the past decades have contributed to
      improvement in transplantation outcomes. To address this question, we conducted a
      registry-based study of adults with acute myeloid leukemia in first or second
      complete remission who underwent allogeneic HCT between 1994 and 2013 from a
      sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for
      HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between
      the 1994-2006 and 2007-2013 periods. Significant improvement in survival was
      observed in the later cohort compared to the earlier cohort for unrelated HCT (P
      = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT
      was solely due to diminished non-relapse mortality (P = 0.001), while incidence
      of relapse did not change over time (P = 0.934). The percentage of patients
      receiving transplants from 8/8-matched unrelated donors was significantly higher
      in the later cohort (P < 0.001), and their survival was significantly better than
      that of those undergoing mismatched unrelated HCT (P = 0.022). These findings
      suggest that advances in HLA-typing technology have been vital for improvement in
      transplantation outcomes.

PMID- 30108331
TI  - Correction: ZFPM2-AS1, a novel lncRNA, attenuates the p53 pathway and promotes
      gastric carcinogenesis by stabilizing MIF.
AB  - Since the online publication of the above article, the authors have noted errors
      in the affiliations. The authors apologise for any inconvenience caused by this
      error. The html and online pdf versions have now been rectified and carry the
      corrected paper.

PMID- 30108333
TI  - Post-injection endophthalmitis in eyes receiving vs. not receiving topical
      antibiotic prophylaxis in Northern Thailand.

PMID- 30108332
TI  - Unbiased shRNA screening, using a combination of FACS and high-throughput
      sequencing, enables identification of novel modifiers of Polycomb silencing.
AB  - Polycomb silencing is an important and rapidly growing field that is relevant to
      a broad range of aspects of human health, including cancer and stem cell biology.
      To date, the regulatory mechanisms for the fine-tuning of Polycomb silencing
      remain unclear, but it is likely that there is a series of unidentified factors
      that functionally modify or balance the silencing. However, a practical gene
      screening strategy for identifying such factors has not yet been developed. The
      failure of screening strategies used thus far is probably due to the effect of
      the loss-of-function phenotypes of these factors on cell cycle progression. Here,
      by applying fluorescence-activated cell sorter (FACS) and high-throughput
      sequencing (HTS) technology in a large-scale lentivirus-mediated shRNA screening,
      we obtained a consecutive dataset from all shRNAs tested, which highlighted a
      substantial number of genes that may control Polycomb silencing. We consider that
      this unbiased strategy can readily be applied to a wide range of studies to
      uncover novel regulatory layers for expression of genes of interest.

PMID- 30108334
TI  - PyMT-1099, a versatile murine cell model for EMT in breast cancer.
AB  - An epithelial-mesenchymal transition (EMT) has been implicated in cancer
      metastasis, drug resistance, and in conferring stem cell-like traits to cancer
      cells. Most studies investigating EMT in cancer have either utilized immortalized
      or cancer cell lines that are already primed to undergo an EMT and do not
      adequately represent a fully differentiated epithelial state in the absence of an
      EMT induction. Hence, model systems are required which recapitulate all stages of
      EMT in cancer cells. Here, we report the derivation and characterization of
      epithelial PyMT-1099 cancer cells from the MMTV-PyMT mouse model of breast
      cancer. We demonstrate that PyMT-1099 cells undergo an EMT upon TGFbeta
      treatment, while upon TGFbeta withdrawal they go through a mesenchymal-epithelial
      transition (MET), as assessed by changes in cell morphology and marker expression
      and comparable to normal murine mammary gland NMuMG cells. However, in contrast
      to NMuMG cells, PyMT-1099 cells show an increase in cell migration and are highly
      tumorigenic and metastatic when transplanted into immunocompromised mice.
      Finally, we report cancer cell-specific changes in gene expression during EMT of
      PyMT-1099 cells not found in non-transformed NMuMG cells. Thus, PyMT-1099 cells
      are a versatile tool to study breast cancer-associated EMT and MET in vitro and
      in vivo.

PMID- 30108335
TI  - Regulation of microRNA function in animals.
AB  - Since their serendipitous discovery in nematodes, microRNAs (miRNAs) have emerged
      as key regulators of biological processes in animals. These small RNAs form
      complex networks that regulate cell differentiation, development and homeostasis.
      Deregulation of miRNA function is associated with an increasing number of human
      diseases, particularly cancer. Recent discoveries have expanded our understanding
      of the control of miRNA function. Here, we review the mechanisms that modulate
      miRNA activity, stability and cellular localization through alternative
      processing and maturation, sequence editing, post-translational modifications of
      Argonaute proteins, viral factors, transport from the cytoplasm and regulation of
      miRNA-target interactions. We conclude by discussing intriguing, unresolved
      research questions.

PMID- 30108336
TI  - Variability in penile duplex ultrasound international practice patterns,
      technique, and interpretation: an anonymous survey of ISSM members.
AB  - Penile duplex ultrasound (PDU), combined with pharmacologic stimulation of
      erection, is the gold standard for the evaluation of multiple penile conditions.
      A 30-question electronic survey was distributed to members of the International
      Society for Sexual Medicine (ISSM). The survey assessed the variability in
      current PDU practice patterns, technique, and interpretation. Chi-square test was
      used to determine the association between categorical variables. Approximately
      9.5% of all 1996 current ISSM members completed the survey. Almost 80% of members
      surveyed reported using PDU, with more North American practitioners utilizing PDU
      than their European counterparts (94% vs 69%, p < 0.01). Approximately 62% of PDU
      studies were performed by a urologist and more than 76% were interpreted by a
      urologist. Although almost 90% of practitioners reported using their own
      protocol, extreme variation in the technique existed among respondents. Over ten
      different pharmacologic mixtures were used to generate erections, and 17% of
      respondents did not repeat dosing for insufficient erection. Urologists
      personally performing PDU were more likely to assess the cavernosal artery flow
      using recommended techniques with the probe at the proximal penile shaft (73% vs
      40%) and at a 60-degree angle or less (68% vs 36%) compared with non-urologists
      (p < 0.01). Large differences in PDU diagnostic thresholds were apparent. Only
      38% of respondents defined arterial insufficiency with a peak systolic velocity <
      25 cm/s, while 53% of respondents defined venous occlusive disease with an end
      diastolic velocity > 5 cm/s. This is the first study to assess the variability in
      the PDU protocol and practice patterns, and to pinpoint areas of improvement. As
      in other surveys, recall bias, generalizability, and response rate (9.5%) are
      inherent limitations to this study. Although most respondents report utilizing a
      standardized PDU protocol, widespread variation exists among practitioners in
      terms of both technique and interpretation, limiting accurate diagnosis and
      appropriate treatment of penile conditions.

PMID- 30108337
TI  - Low-intensity shockwave therapy for erectile dysfunction in kidney transplant
      recipients. A prospective, randomized, double blinded, sham-controlled study with
      evaluation by penile Doppler ultrasonography.
AB  - OBJECTIVES: To study the efficacy of Low intensity Extracorporeal Shockwave
      Therapy (Li- ESWT) for the treatment of erectile dysfunction (ED) in kidney
      transplanted men. METHODS: Twenty men (mean age = 53.7 years) were selected. This
      was a double-blinded, prospective, randomized, sham-controlled trial. The ESWT
      protocol was based in a 2 treatment sessions per week for 3 weeks. The sham
      treatment was performed using the same device replacing the effective probe for
      one that emits zero energy. Baseline and follow-up assessment was performed with
      International Index of Erectile Function Questionnaire (IIEF) score and Erection
      Hardness Score (EHS) after 1, 4 and 12 months. Penile Doppler was performed
      before and after treatment. RESULTS: A total of 20 patients were recruited, 10
      patients in each group. Baseline scores were similar. The mean EHS in after 1
      month were 2.5 +/- 0.85 (Li-EWST) and 2.4 +/- 0.7 (Sham therapy), p = 0.724 .
      After 4 months it was 2.4 +/- 0.7 and 2.6 +/- 0.84, p = 0,0004 (between the
      moments) . The baseline IIEF score was 14.9 +/- 3(Sham Theraphy) and 10.9 +/- 5.1
      (Li-EWST). The mean IIEF score after 1 month was 15.6 +/- 6.1 (Li-EWST) and 16.6
      +/- 5.4 (Sham therapy). The mean IIEF score after 4 months was 17.2 +/- 5.7 (Li
      EWST) and 16.5 +/- 5 (Sham therapy), p < 0.0001 (between the moments). IIEF score
      improvement was higher than 5 in 70% (ranged from 0-10) and in 10% (ranged from 1
      14) in Li-ESWT and Sham groups, respectively. The mean change in IIEF score after
      12 months was 4.8 in Li-ESWT group .Penile Doppler parameters were similar
      between groups and did not present improvements. CONCLUSIONS: Li-ESWT is a
      treatment with clinical efficacy. Despite evidences suggesting neoagiogenesis,
      our short protocol had no impact in penile Doppler parameters.

PMID- 30108338
TI  - Publisher Correction: Single-DNA electron spin resonance spectroscopy in aqueous
      solutions.
AB  - In the version of this paper originally published online, the ORCID ID for Peter
      Z. Qin was incorrectly assigned to Zhuoyang Qin. In addition, the ORCID for
      Fazhan Shi was omitted. These errors have been corrected in the print, PDF, and
      HTML versions of the paper.

PMID- 30108339
TI  - Organ memory: a key principle for understanding the pathophysiology of
      hypertension and other non-communicable diseases.
AB  - In recent years, several post-interventional analyses of large-scale randomized
      controlled clinical trials have given us a new concept regarding the risk
      management of hypertension and cardiovascular diseases. The beneficial effects of
      intensive treatments were extended even after the interventions ended. This
      phenomenon is known as "metabolic memory" or "legacy effect", and we recognized
      its clinical significance. A certain level of evidence in human and animal
      studies employing organ transplantation techniques has indicated that this type
      of "memory" resides in each organ and could be transferrable, erasable, and
      rewritable, which is similar to neuronal and immune "memory". In this review, we
      define this memory as "organ memory" and summarize the current picture and future
      direction of this concept. "Organ memory" can be observed in many clinical
      settings, including in the control of hypertension, diabetes mellitus, and
      dyslipidemia. Several intensive treatments were demonstrated to have the
      potential to rewrite "organ memory", leading to the curability of targeted
      diseases. "Organ memory" is the engraved phenotype of altered organ
      responsiveness acquired by a time-dependent accumulation of organ stress
      responses. Not only is the epigenetic change of key genes involved in the
      formation of "organ memory" but the alteration of multiple factors, including low
      molecular weight energy metabolites, immune mediators, and tissue structures, is
      involved as well. These factors intercommunicate during every stress response and
      carry out incessant remodeling in a certain direction in a spiral fashion through
      positive feedback mechanisms. Future studies should be directed toward the
      identification of the core unit of "organ memory" and its manipulation.

PMID- 30108340
TI  - Never give up correcting your lifestyle! The beginning is always the hardest!

PMID- 30108341
TI  - Calprotectin and necrotizing enterocolitis: it's not the assay, it's the
      definition.

PMID- 30108343
TI  - Vitamin D and associated perinatal-neonatal outcomes among extremely low-birth
      weight infants.
AB  - OBJECTIVE: To evaluate vitamin D inadequacy among extremely low-birth-weight
      (ELBW, <1000 g) infants and the association between circulating vitamin D
      concentrations and perinatal-neonatal outcomes. STUDY DESIGN: Prospective cohort
      study of ELBW infants in the neonatal ICU. Blood was collected within the first 3
      days after birth after obtaining informed consent. Circulating 25-hydroxyvitamin
      D concentrations (25(OH)D) were quantified using liquid chromatography-tandem
      mass spectroscopy and classified as vitamin D deficient, insufficient, or
      adequate ( < 20, 20-30, or > 30 ng/mL, respectively). Associations between
      25(OH)D and perinatal-neonatal outcomes were determined by multivariable
      regression, adjusted for covariates that differ in the bivariate analysis.
      RESULTS: Of the 60 ELBW infants enrolled, 13 (22%) were vitamin D deficient, 15
      (25%) were insufficient, and 32 (53%) were adequate. 25(OH)D levels were
      positively associated with fetal growth restriction and prolonged rupture of the
      membranes. CONCLUSIONS: Vitamin D inadequacy was frequent among ELBW infants.
      Circulating vitamin D concentrations were significantly associated with perinatal
      outcomes in this contemporary cohort.

PMID- 30108344
TI  - Stress during pregnancy, gestational weight gain, and body mass index.

PMID- 30108342
TI  - Whole-exome sequencing in fetuses with central nervous system abnormalities.
AB  - OBJECTIVE: We describe our experience with whole-exome sequencing (WES) in
      fetuses with central nervous system (CNS) abnormalities following a normal
      chromosomal microarray result. METHODS: During the study period (2014-2017) 7
      cases (9 fetuses) with prenatally diagnosed CNS abnormality, whose chromosomal
      microarray analysis was negative, were offered whole-exome sequencing analysis.
      RESULTS: A pathogenic or a likely pathogenic variant was found in 5 cases
      including a previously described, likely pathogenic de novo TUBA1A variant (Case
      #1); a previously described homozygous VRK1 variant (Case #2); an X-linked ARX
      variant (Case #3); a likely pathogenic heterozygous variant in the TUBB3 gene
      (Case #5). Finally, in two fetuses of the same couple (Case #6), a compound
      heterozygous state was detected, consisting of the NPHP1 gene deletion and a
      sequence variant of uncertain significance. Two additional cases had normal WES
      results. CONCLUSION: Whole-exome sequencing may improve prenatal diagnosis in
      fetuses with CNS abnormalities.

PMID- 30108346
TI  - Advancing micro-scale cooling by utilizing liquid-liquid phase separation.
AB  - Achieving effective cooling within limited space is one of the key challenges for
      miniaturized product design. State-of-the-art micro-scale cooling enhancement
      techniques incorporate flow disturbances and boiling to reach high performance.
      However, these methods face the inherent issues of extra pressure drop, flow
      instability and dry-out that limits heat flux. Here we demonstrate that
      substantial cooling capability enhancement, up to 2.5 times, is realized by
      introducing the phase separation of a triethylamine (TEA)/water mixture at the
      micro-scale. Our experiments show that the enhancement behavior is closely
      related to the system's initial composition, temperature, and flow conditions.
      Moreover, the mixture system exhibits reduced pressure drop after separation,
      which makes it more promising in serving practical applications. The results
      reveal new possibilities for liquid coolant selection and provide the
      experimental foundation for further research in this area.

PMID- 30108347
TI  - War zone complicates roll-out of Ebola vaccine in latest outbreak.

PMID- 30108345
TI  - Engineering of Primary Human B cells with CRISPR/Cas9 Targeted Nuclease.
AB  - B cells offer unique opportunities for gene therapy because of their ability to
      secrete large amounts of protein in the form of antibody and persist for the life
      of the organism as plasma cells. Here, we report optimized CRISPR/Cas9 based
      genome engineering of primary human B cells. Our procedure involves enrichment of
      CD19+ B cells from PBMCs followed by activation, expansion, and electroporation
      of CRISPR/Cas9 reagents. We are able expand total B cells in culture 10-fold and
      outgrow the IgD+ IgM+ CD27- naive subset from 35% to over 80% of the culture. B
      cells are receptive to nucleic acid delivery via electroporation 3 days after
      stimulation, peaking at Day 7 post stimulation. We tested chemically modified
      sgRNAs and Alt-R gRNAs targeting CD19 with Cas9 mRNA or Cas9 protein. Using this
      system, we achieved genetic and protein knockout of CD19 at rates over 70%.
      Finally, we tested sgRNAs targeting the AAVS1 safe harbor site using Cas9 protein
      in combination with AAV6 to deliver donor template encoding a splice acceptor
      EGFP cassette, which yielded site-specific integration frequencies up to 25%. The
      development of methods for genetically engineered B cells opens the door to a
      myriad of applications in basic research, antibody production, and cellular
      therapeutics.

PMID- 30108348
TI  - G ene-silencing technology gets first drug approval after 20-year wait.

PMID- 30108350
TI  - Enzymes team up with light-activated catalysts.

PMID- 30108351
TI  - From the archive.

PMID- 30108352
TI  - How digital drug users could help to halt the US opioid epidemic.

PMID- 30108354
TI  - Speed up global ban on industrial trans fats in food.

PMID- 30108353
TI  - Biologists ignore ocean weather at their peril.

PMID- 30108355
TI  - Dilemma over AI and drug patenting already under debate.

PMID- 30108356
TI  - Bring training forward for undergraduate researchers.

PMID- 30108357
TI  - Engage more early-career scientists as peer reviewers.

PMID- 30108358
TI  - Funders must be wary of industry alliances.

PMID- 30108359
TI  - Industry trumps peer-reviewed science at US environment agency.

PMID- 30108360
TI  - LHC physicists embrace brute-force approach to particle hunt.

PMID- 30108361
TI  - Publisher Correction: Late-surviving stem mammal links the lowermost Cretaceous
      of North America and Gondwana.
AB  - The asterisked footnote to Extended Data Table 1 should state '*Including
      Thomasia and Haramiyavia'. This has been corrected online.

PMID- 30108362
TI  - Author Correction: Cryo-EM structure of a fungal mitochondrial calcium uniporter.
AB  - In this Article, ref. 15 has been replaced and references 32 to 50 have been
      renumbered online.

PMID- 30108363
TI  - Author Correction: Observation of half-integer thermal Hall conductance.
AB  - In this Article, the publication details for references 33, 34 and 40 have been
      corrected online.

PMID- 30108365
TI  - Taking the STING out of inflammation.

PMID- 30108366
TI  - HMGB1+ platelet microparticles damage the endothelium.

PMID- 30108367
TI  - B cell therapy in ANCA-associated vasculitis: current and emerging treatment
      options.
AB  - Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an
      organ-threatening and life-threatening multi-system autoimmune disease in which B
      cell-derived ANCAs cause neutrophil activation and endothelial damage, strongly
      implicating these autoantibodies in the pathogenesis of AAV. B cell depletion
      with rituximab combined with glucocorticoids is associated with a reduction in
      ANCA concentrations and with clinical remission in the majority of patients with
      AAV. However, the safety profile of rituximab is no better than that of
      conventional therapy with cyclophosphamide, and long-term glucocorticoid
      treatment is needed to achieve and maintain disease-free remission. A need for
      new therapies exists to reduce the time to remission, to spare the use of
      glucocorticoids and to promote long-lasting remission without the risk of
      relapse. Over the past 20 years, there has been great interest in therapeutically
      targeting B cell cytokines, such as B cell-activating factor (BAFF), in many
      autoimmune disease settings. Dual B cell-targeted immunotherapy that combines B
      cell depletion and BAFF blockade could potentially be more efficacious than
      targeting either mechanism alone. In this Review, the theoretical background for
      use of this combination approach in AAV is presented and discussed.

PMID- 30108364
TI  - Author Correction: Ancient hepatitis B viruses from the Bronze Age to the
      Medieval period.
AB  - In Fig. 2 of this Letter, the 'E' and 'G' clade labels were inadvertently
      reversed, and in Table 2 the genotype of DA27 was 'D1' instead of 'D5'. These
      have been corrected online.

PMID- 30108368
TI  - Tributyltin Inhibits Neural Induction of Human Induced Pluripotent Stem Cells.
AB  - Tributyltin (TBT), one of the organotin compounds, is a well-known environmental
      pollutant. In our recent study, we reported that TBT induces mitochondrial
      dysfunction, in human-induced pluripotent stem cells (iPSCs) through the
      degradation of mitofusin1 (Mfn1), which is a mitochondrial fusion factor.
      However, the effect of TBT toxicity on the developmental process of iPSCs was not
      clear. The present study examined the effect of TBT on the differentiation of
      iPSCs into the ectodermal, mesodermal, and endodermal germ layers. We found that
      exposure to nanomolar concentration of TBT (50 nM) selectively inhibited the
      induction of iPSCs into the ectoderm, which is the first step in neurogenesis. We
      further assessed the effect of TBT on neural differentiation and found that it
      reduced the expression of several neural differentiation marker genes, which were
      also downregulated by Mfn1 knockdown in iPSCs. Taken together, these results
      indicate that TBT induces developmental neurotoxicity via Mfn1-mediated
      mitochondrial dysfunction in iPSCs.

PMID- 30108370
TI  - Making the first move in EGFR-driven or ALK-driven NSCLC: first-generation or
      next-generation TKI?
AB  - The traditional approach to the treatment of patients with advanced-stage non
      small-cell lung carcinoma (NSCLC) harbouring ALK rearrangements or EGFR mutations
      has been the sequential administration of therapies (sequential treatment
      approach), in which patients first receive first-generation tyrosine-kinase
      inhibitors (TKIs), which are eventually replaced by next-generation TKIs and/or
      chemotherapy upon disease progression, in a decision optionally guided by tumour
      molecular profiling. In the past few years, this strategy has been challenged by
      clinical evidence showing improved progression-free survival, improved
      intracranial disease control and a generally favourable toxicity profile when
      next-generation EGFR and ALK TKIs are used in the first-line setting. In this
      Review, we describe the existing preclinical and clinical evidence supporting
      both treatment strategies - the 'historical' sequential treatment strategy and
      the use of next-generation TKIs - as frontline therapies and discuss the
      suitability of both strategies for patients with EGFR-driven or ALK-driven NSCLC.

PMID- 30108369
TI  - Snake fungal disease alters skin bacterial and fungal diversity in an endangered
      rattlesnake.
AB  - Snake Fungal Disease (SFD), caused by Ophidiomyces ophiodiicola, is the most
      recently described fungal disease afflicting wildlife populations across North
      America and Europe. It has been proposed as a significant conservation threat
      yielding high mortality and yet much its ecology is unknown. We collected 144
      skin swabs from Eastern Massasaugas (Sistrurus catenatus) in 2015 and 2016 to
      determine document ongoing prevalence and assess differences in microbial
      assemblages between positive and negative individuals. Alpha diversity of fungi
      was reduced in SFD positive animals, while beta diversity identified distinct
      assemblages of microbes between SFD-positive and -negative samples. Ophidiomyces
      was present on the skin of affected animals, even on body sites distant to
      lesions indicating that the microbiome on entire surface of the skin is altered.
      Ophidiomyces was not detected in any non-SFD snake. There were smaller, but
      significant, influences of year sampled. Bacterial genera Janthinobacterium and
      Serratia were significantly increased in SFD snakes, while Xylanimicrobium,
      Cellulosimicrobium, and Rhodococcus were the only bacterial taxa significantly
      reduced. The relative abundance of fungi within the orders Pleosporales and
      Canopdiales was reduced in SFD-positive samples, though Pyrenochaetopsis pratorum
      was the only species found to differ significantly. This is the first study to
      determine the impact that this fungal pathogen has on the skin microbiome.

PMID- 30108371
TI  - The molecular chaperon AKR2A increases the mulberry chilling-tolerant capacity by
      maintaining SOD activity and unsaturated fatty acids composition.
AB  - Chilling is common in nature and can damage most plant species, particularly
      young leaves and buds. Mulberry (Morus spp.) is an economically important food
      source for the domesticated silkworm (Bombyx mori). However, weather and climatic
      extremes, such as "late spring coldness", seriously damage mulberry buds and
      young leaves. The molecular mechanism involved in the differing mulberry chilling
      tolerance is unclear. In the present study, we found that mSOD1, mFADII, and
      mKCS1 interacted with mAKR2A and that the expression of mAKR2A, mSOD, mFAD, and
      mKCS1 in the chilling-tolerant mulberry variety was higher than that in the
      chilling-sensitive variety. Unsaturated fatty acids content and superoxide
      dismutase (SOD) activity in the chilling-tolerant variety was higher than that in
      the chilling-sensitive variety. After chilling treatment, mSOD1, mKCS1 and mAKR2A
      expression in the chilling-tolerant variety was reduced to lower than that in the
      chilling-sensitive variety, whereas mFADII expression increased in the chilling
      tolerant variety compared with that in the chilling-sensitive variety, suggesting
      that the increased expression of the molecular chaperon mAKR2A helped to maintain
      or prompted the chilling-related proteins in the chilling-tolerant variety.

PMID- 30108372
TI  - Hairs in old books isotopically reconstruct the eating habits of early modern
      Japan.
AB  - To complement literature-based historical knowledge of the eating habits of 17th-
      and 18th-century Japan, we analysed carbon and nitrogen isotope ratios (delta13C
      and delta15N, respectively) of human hairs embedded in cover paper of Japanese
      books printed during 1690s-1890s, taking regional and temporal variations into
      consideration. We purchased 24 book sets from second-hand book markets. Twenty
      three sets contained enough human hairs, which were non-destructively extracted
      from the thick, recycled paper of the book covers and used to measure the
      delta13C and delta15N values, found to be identical within each book set.
      Relatively low delta13C values and high delta15N values suggested that people
      depended on rice, C3 vegetables, and fish, more exclusively than contemporary
      Japanese people. The relatively high delta13C values found in Edo (Tokyo) might
      be associated with the preference for C4 millets by Edo people as a measure
      against beriberi (locally recognised as the Edo affliction). The delta15N values
      gradually increased over 200 years, indicating an increase in the contribution of
      marine fish both as food and fertiliser for rice fields as suggested by
      literature-based studies. Further collection of hairs from books will enable a
      thorough examination of regional and temporal variations to better understand the
      pre-globalised food culture.

PMID- 30108373
TI  - Prostate cancer risk factors in black and white men in the NIH-AARP Diet and
      Health Study.
AB  - BACKGROUND: There are few prospective studies comparing race-specific
      associations between diet, nutrients, and health-related parameters, and prostate
      cancer risk. METHODS: Race-specific prostate cancer risk associations were
      examined among men in the National Institutes of Health (NIH)-AARP Diet and
      Health Study. We identified 1417 cases among black men (209 advanced), and 28,845
      among white men (3898 advanced). Cox proportional hazards regression models
      estimated hazard ratios (HRs) and 95% confidence intervals (CIs). We also
      evaluated the cumulative change in the HR for black race following adjustment for
      each factor. RESULTS: Race-specific prostate cancer associations were similar in
      black and white men across disease subtypes only for history of diabetes (overall
      : HR = 0.77, 95% CI: 0.65-0.90 and HR = 0.72, 95% CI: 0.69-0.76, respectively;
      Pinteraction = 0.66). By contrast, there was a positive risk association with
      height for white men  and  inverse for black men (Pinteraction: non-advanced =
      0.01; advanced = 0.04). This difference remained among men with at least 2 years
      of follow-up for non-advanced (Pinteraction = 0.01), but not advanced disease
      (Pinteraction = 0.24); or after adjustment for prostate cancer screening (non
      advanced Pinteraction = 0.53, advanced Pinteraction = 0.31). The only other
      evidence of interaction with race was observed for dietary vitamin D intake and
      non-advanced disease, but only after adjustment for screening (Pinteraction =
      0.02). Cumulative adjustment for each factor increased the HR for black race by
      32.9% for overall cancer and 12.4% for advanced disease. CONCLUSIONS: Our data
      suggest few of the dietary, nutrient, and health-related factors associated with
      prostate cancer risk in predominantly non-Hispanic white men were associated with
      risk in black men, and adjustment for these factors widen the black-white
      difference in risk. Larger studies of black men, particularly with prospective
      data, are needed to help identify risk factors relevant to this population.

PMID- 30108374
TI  - Incidence and risk factors of suicide after a prostate cancer diagnosis: a meta
      analysis of observational studies.
AB  - BACKGROUND: Whether the diagnosis of prostate cancer is a contributory
      psychological stress that causes excess risk of suicide among affected men
      remains controversial. We performed a meta-analysis of previous studies to
      investigate suicide incidence and associated risk factors among men diagnosed
      with prostate cancer. METHODS: The MEDLINE, Embase, Cochrane Library, and
      PsycINFO databases were searched to identify eligible studies published before
      April 2018. The inverse variance method with random-effects modeling was used to
      calculate summary relative risks (RRs) and their associated 95% confidence
      intervals (CIs). RESULTS: Eight observational studies involving 1,281,393 men
      diagnosed with prostate cancer and 842,294 matched prostate cancer-free men were
      included. An overall increased RR of suicide of 2.01 (95% CI: 1.52-2.64; P <
      0.001; I2 = 91.8%) was observed among men diagnosed with prostate cancer compared
      with those without prostate cancer during the first year, especially during the
      first 6 months (RR = 2.24, 95% CI: 1.77-2.85; P < 0.001; I2 = 61.1%) after
      diagnosis. Moreover, prostate cancer patients were at an increased risk of
      suicide among men aged 75 years or older (RR = 1.51, 95% CI: 1.04-2.18; P =
      0.028; I2 = 91.5%) and treated with hormonal therapy (RR = 1.80, 95% CI: 1.54
      2.12; P < 0.001; I2 = 0%). Furthermore, marital status, race, disease risk
      category, and socioeconomic status were not associated with increased suicide
      risk in men with prostate cancer. CONCLUSIONS: Current evidence indicates that
      the risk of suicide is increased among men diagnosed with prostate cancer,
      particularly those aged 75 years or older, <12 months after diagnosis, and
      treated with hormonal therapy. Healthcare providers should be aware of these
      special populations considered at high risk of suicide. Hence, further research
      should be conducted to refine suicide risk assessment with detection tools and to
      develop the best practices for prevention.

PMID- 30108376
TI  - Accuracy of the magnetic resonance imaging pathway in the detection of prostate
      cancer: a systematic review and meta-analysis.
AB  - BACKGROUND: Although magnetic resonance imaging and subsequent targeted biopsy
      ('MRI pathway') have been widely adopted in routine clinical practice, it is
      still a common practice to perform systematic biopsy concurrently, because the
      accuracy of the MRI pathway is yet to be fully defined. This systematic review of
      the literature assessed the sensitivity of the MRI pathway for detecting
      clinically significant prostate cancer. METHODS: Multiple databases were searched
      up to May 2017 according to the Preferred Reporting Items for Systematic Review
      and Meta-analysis (PRISMA) statement for studies assessing the accuracy of MR
      guided biopsy (MRGB) compared to a reference standard which consisted of both
      MRGB and systematic biopsy with at least 20-cores. The primary outcome was the
      sensitivity of detecting clinically significant prostate cancer defined as
      Gleason >=7 disease. RESULTS: A total of 15 studies met the predefined inclusion
      criteria. Overall, studies were assessed to be of low quality with inadequate
      blinding of personnel, which could introduce performance and detection bias. The
      calculated summary sensitivity of the MRI pathway was 78.3% [95%CI 75.0-81.4%].
      There was moderate heterogeneity between the included studies (I2 = 36%).
      Subgroup analysis was performed based on clinical setting, the strength of MRI
      magnet and mode of image fusion as factors but no interaction was identified
      between any of the subgroups. No publication bias was identified. CONCLUSION: The
      MRI pathway cannot yet be solely relied upon to diagnose clinically significant
      disease and hence additional systematic sampling should still be performed during
      the biopsy procedure.

PMID- 30108375
TI  - Role of the 4Kscore test as a predictor of reclassification in prostate cancer
      active surveillance.
AB  - BACKGROUND: Management of active surveillance (AS) in low-risk prostate cancer
      (PCa) patients could be improved with new biomarkers, such as the 4Kscore test.
      We analyze its ability to predict tumor reclassification by upgrading at the
      confirmatory biopsy at 6 months. METHODS: Observational, prospective, blinded,
      and non-randomized study, within the Spanish National Registry on AS
      (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and
      inclusion criteria: PSA <=10 ng/mL, cT1c-T2a, Grade group 1, <=2 cores, and <=5
      mm/50% length core involved. Central pathological review of initial and
      confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6
      months after initial Bx and just before confirmatory Bx to determine 4Kscore
      result. In order to predict reclassification defined as Grade group >=2, we
      analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA
      density, family history, body mass index, initial Bx, total cores, initial Bx
      positive cores, initial Bx % of positive cores, initial Bx maximum cancer core
      length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non
      parametric trend test or Fisher's exact test, as appropriate established
      differences between groups of reclassification. RESULTS: A total of 137 patients
      met inclusion criteria. Eighteen patients (13.1%) were reclassified at
      confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the
      groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we
      found a sensitivity of 89% and a specificity of 29%, with no reclassifications to
      Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group
      2 reclassified patients. Using this threshold value there is a biopsy reduction
      of 27%. Additionally, 4Kscore was also associated with changes in tumor volume.
      CONCLUSIONS: Our preliminary findings suggest that the 4Kscore may be a useful
      tool in the decision-making process to perform a confirmatory Bx in active
      surveillance management.

PMID- 30108377
TI  - Contextualizing disability: a cross-sectional analysis of the association between
      the built environment and functioning among people living with spinal cord injury
      in the United States.
AB  - STUDY DESIGN: Secondary analysis of cross-sectional data from a multisite cohort
      study. OBJECTIVES: To analyze the association between the built environment and
      physical functioning reported by adults living with chronic spinal cord injury
      (SCI). SETTING: Four US Spinal Cord Injury Model Systems centers in New Jersey,
      Colorado, Illinois, and Michigan. METHODS: Participants were from the Spinal Cord
      Injury-Functional Index/Capacity (SCI-FI/C) development study. Survey data from N
      = 402 participants were geocoded for analysis. Geographic Information Systems
      (GIS) analysis was used to define five- and half-mile buffer areas around
      participants' residential addresses to represent the community and neighborhood
      environments, respectively, and to create measures of land use, residential
      density, destination density, and park space. The relationships between these
      built environment features and four domains of physical functioning-basic
      mobility, wheelchair mobility, self-care, and fine motor function-were modeled
      using ordinary least squares (OLS) regression. RESULTS: People with paraplegia
      living in neighborhoods with more destinations and a nearby park reported higher
      levels of self-care functioning. For people with tetraplegia, living in a
      community with more destinations was associated with better wheelchair mobility
      and fine motor functioning, and living in a neighborhood with high land use mix
      was associated with higher fine motor functioning scores. CONCLUSIONS: The
      association between the built environment and functioning after SCI is supported
      and in need of further investigation. Understanding the environmental context of
      disability may lead to community-based interventions and effective public policy
      that will attenuate the experience of limitations and promote accessibility on a
      larger scale.

PMID- 30108378
TI  - Pancreatitis in children: A diagnosis missed in Pakistan?

PMID- 30108379
TI  - Multiple dimensions of violence against healthcare providers in Karachi: Results
      from a multicenter study from Karachi.
AB  - OBJECTIVE: To investigate the causes, consequences and possible solutions for
      violence against healthcare. METHODS: The qualitative study was conducted in
      Karachi June 2015 to December 2015 using in-depth interviews and focus groups
      discussions with all stakeholders. Transcription was done verbatim using both
      audio and videotapes of all the sessions. First open coding was done using
      inductive analyses by 3 researchers. After consensus, these codes were used for
      thematic content analysis. Interviews and discussions were stopped after
      saturation was reached and no new codes were identified.. RESULTS: Overall, 42 in
      depth interviews and 17 focus groups discussions were held. Major forms of
      physical violence included beating, throwing things, abusive language, threats,
      harassment, damage to building, furniture, vehicles and equipment. The threshold
      of violence was very high for verbal violence and minor forms of physical
      violence. The causes were identified as behavioural (communication gap between
      providers and patients, attendants), institutional (capacity, resources and
      systems) and socio-political (growing illiteracy and intolerance). The sequelae
      of violence included guilt, night dreams, shame and 61.9 % (N=26/42 IDIs)% who
      faced violence did not report it officially. CONCLUSIONS: Violence faced by
      healthcare providers was multifaceted and needs interventions at varied levels,
      including training of healthcare staff in dealing with violence and its
      aftermaths, security measures at the healthcare institutions inclusive of
      ambulance services and policies at the national level to manage and de-escalate
      violence against healthcare.

PMID- 30108380
TI  - Urdu translation and validation of PHQ-9, a reliable identification, severity and
      treatment outcome tool for depression.
AB  - OBJECTIVE: To translate and validate the self-report brief version of Patient
      Health Questtionaire-9 in Urdu. METHODS: The descriptive study was carried out at
      the Combined Military Hospitals in Gilgit and Lahore, and Pakistan Naval Ship
      Shifa Hospital in Karachi, from February to May 2016, and comprised of patients
      recruited from primary healthcare centres of the three cities Standardised
      procedures including forward-translation, back-translation, expert panel
      discussion, face validation, pilot testing, and target population validation were
      done. SPSS 21 was used for statistical analysis. RESULTS: Of the 293 patients,
      164(56%) were males and 129(44%) were females. Exploratory factor analysis
      revealed a single factor solution with minimum factor loading being 0.63.
      Cronbach's alpha for the scale was 0.91 and split-half reliability was 0.77.
      Females were more likely to have depressive symptoms compared to male
      participants (p<0.01). Participants' area of dwelling also influenced their
      reported symptoms (p<0.01). CONCLUSIONS: Patient Health Questtionaire-9 Urdu
      scale was found to be a valid and reliable tool to screen, rate and monitor
      outcomes of depressive illness in primary healthcare settings in Pakistan.

PMID- 30108381
TI  - Prevalence of undiagnosed type 2 diabetes mellitus in Pakistan: Results of screen
      diabetes disease registry.
AB  - OBJECTIVE: To estimate the prevalence of undiagnosed diabetes in patients
      visiting the primary care physicians for any reason in urban outpatient settings.
      METHODS: This national, multicentre, non-interventional disease registry was
      conducted from October 2011 to August 2013 across Sindh and Punjab provinces of
      Pakistan and comprised randomly selected health centres with qualified general
      practitioners. Patients aged 45 years or more and willing to have a random blood
      sugar screening test were selected. They were screened on American Diabetes
      Association risk factors. Fasting blood glucose and glycated haemoglobin of
      patients with random blood sugar >200 mg/dL were checked and those with values
      >126 mg/dL or >6.5% respectively were considered newly-diagnosed type diabetics
      T2DM. They were followed up three months later. RESULTS: There were 8,250
      patients with a mean age of 53.2+/-8.1 years, and mean body mass index of 27.3+/
      5.3kg/m2. The prevalence of undiagnosed diabetes in patients visiting primary
      care physicians for any reason was 525(6.4%). Overall, 484(92.2%) of the newly
      diagnosed type 2 diabetics were advised lifestyle modification, 460(88.1%) were
      put on oral anti-diabetic drugs, and insulin was initiated in 50(9.5%) patients.
      There was a mean decrease of 1.6+/-1.6%in glycated haemoglobin and 41.9+/
      56.8mg/dL in fasting blood glucose from baseline to the three-month follow-up.
      CONCLUSIONS: The burden of undiagnosed diabetes in Pakistan was found to be
      considerable. With proper management, significant improvement was shown.

PMID- 30108382
TI  - Spectrum of renin angiotensin aldosterone system disorders in young
      hypertensives.
AB  - OBJECTIVE: To analyse the spectrum of renin angiotensin aldosterone system
      disorders in young hypertensive patients in hospital settings. METHODS: This
      cross-sectional study was conducted at the Department of Chemical Pathology and
      Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from
      January to December, 2016. It comprised hypertensive subjects aged 17-40 years of
      either gender presenting in the outpatient department. All subjects were having
      blood pressure more than 140/90mmHg and were not on any anti-hypertensive
      medicine. Blood sample was taken from each patient to analyse arterial blood
      gases, plasma renin, serum aldosterone and electrolytes. Association of
      qualitative variables like age, systolic and diastolic blood pressure with
      essential hypertension and primary hyperaldosteronism was explored. RESULTS: Of
      the 80 patients, 72(90%) were diagnosed with essential hypertension and 8(10%)
      with primary hyperaldosteronism. None of the patients had Liddle syndrome,
      apparent mineralocorticoid excess or Gordon syndrome. Mean age of patients having
      essential hypertension was 30.97+/-7.1 years, whereas, for those with primary
      hyperaldosteronism it was 29.25+/-7.1 years. Systolic blood pressure was
      significantly higher (p = 0.000) among all patients. No statistically significant
      association was found between age, systolic and diastolic blood pressure
      (p<0.05). CONCLUSIONS: Primary hyperaldosteronism as compared to other renin
      angiotensin aldosterone system disorders was found to be the leading cause of
      hypertension in young population.

PMID- 30108383
TI  - Perception of problem solving skills in cancer patients according to certain
      variables and control focus.
AB  - OBJECTIVE: To determine the perception of problem-solving skills in cancer
      patients related to control focus. METHODS: This cross-sectional descriptive
      study was conducted at the Manisa State Hospital, Manisa, Turkey, between May and
      December 2015, and comprised outpatients monitored by the Radiation Oncology
      department. Focus of control scale, problem solving inventory and a self
      generated socio-demographic form were used as data collection instruments. SPSS
      15 was used for data analysis. RESULTS: Of the 263 subjects, 133(50.6%) were
      women and 130(49.4%) were men with an overall mean age of 56.98+/-12.32 years.
      Personality characteristics and their type of control focus affected problem
      solving skill (p<0.05). Gender, education level, income level, and status of
      obtaining help from family-type health professionals had an effect on their
      control focus type and problem solving (p<0.05). CONCLUSIONS: Personality
      characteristics and their type of focus influenced perception of problem solving
      in cancer patients.

PMID- 30108384
TI  - Assessment of contamination on sterilised dental burs after being subjected to
      various pre-cleaning methods.
AB  - OBJECTIVE: To determine the effectiveness of different pre-cleaning methods by
      determining frequency and site of contamination on the sterilised dental burs
      using Phloxine B dye. METHODS: The in-vitro experimental study was conducted from
      June to August 2017 at dental clinics of Aga Khan University Hospital Karachi.
      Diamond dental burs were selected and divided into two control and four test
      groups. The two control groups were classified as Negative (new burs) and
      Positive (used contaminated). The four test groups were classified as Manual
      (Group-1), Ultrasonic (Group-2), Manual + Enzyme (Group-3) and Manual +
      Ultrasonic (Group-4). Phloxine B dye was used to determine the contamination. The
      images of the burs were taken and enlarged at 15X before subjected to visual
      assessment. Association between contamination and pre-cleaning methods were
      determined. Data was analysed using SPSS version 22. RESULTS: A total of 210 burs
      were selected for the study which were divided in 6 groups of 35(16.66%) each.
      One (2.8%) bur in negative control group and all burs in positive control group
      showed contamination. In test groups, 27(77.1%), 29(82.8%), 27(77.1%) and
      24(68.5%) burs showed contamination in groups 1, 2, 3 and 4, respectively. There
      was no association between type of pre-cleaning method with the frequency of
      contamination (p =0.57). The head of bur was the most frequently contaminated
      site (p < 0.003). CONCLUSIONS: None of the pre-cleaning method was found to be
      effective. Head of bur was the most frequently contaminated site.

PMID- 30108385
TI  - Oesophageal foreign bodies caused by meat consumed during the Sacrifice Feast:
      Our single-centre experience.
AB  - OBJECTIVE: To compare the frequency of oesophageal foreign bodies during the
      month of Eid-ul-Adha with other months. METHODS: This retrospective study was
      conducted at YuzuncuYil University Hospital, Van, Turkey, during 2012-16, and
      comprised individuals who were treated for bone and/or meat fragments lodged in
      the oesophagus. The number of hospital admissions with diagnosis of oesophageal
      foreign bodies during Eid-ul-Adha episodes were extricated and compares with
      similar date for the other months.Minitab 13 was used for statistical
      computations. RESULTS: Among the 289 cases in the study, a pronounced increase in
      the number of patients was observed during Eid-ul-Adha, with the most frequent
      symptoms in 263(91%) patients being dysphagia and odynophagia. The number of
      patients with oesophageal foreign bodies diagnosed during Eid-ul-Adha were
      significantly higher than the other months (p<0.05). CONCLUSIONS: An increase in
      cases of oesophageal foreign bodies was found during Eid-ul-Adha.

PMID- 30108386
TI  - Short-term outcome of clinical and histopathologic variants of mesangiocapillary
      glomerulonephritis in children: A retrospective analysis from a tertiary care
      center.
AB  - OBJECTIVE: To study the frequency, clinicopathological features and short-term
      outcome of mesangiocapillary glomerulonephritis (MCGN) in children at a tertiary
      care kidney center in Pakistan. METHODS: A descriptive, observational study was
      conducted at the Paediatric Nephrology Department, Sindh Institute of Urology and
      Transplantation, Karachi, from January 2011 till December 2015. A review of all
      paediatric (<18 years) renal biopsies during the study period was performed and
      cases of MCGN were enrolled. The clinical presentation, laboratory findings,
      histology and outcome were analyzed. RESULTS: During the study period, 890
      paediatric renal biopsies were performed. Of these, 63(7%) were MCGN. Among
      these, 34(54%) were males and 29 (46%) females. Mean age was 9.9 +/- 3.2years.
      Thirty four (54%) presented with nephrotic syndrome (NS), and29 (46%) with
      rapidly progressive glomerulonephritis (RPGN).Mean duration of follow-up was 1.66
      +/- 1.34 years. Outcome of patients with NS with renal failure (RF)was complete
      remission (CR) in 1(7.7%), persistent proteinuria with normal renal functions in
      1(7.7%),chronic kidney disease (CKD) in 3 (23%), end-stage renal disease (ESRD)
      in 4 (30.8%), while 4 (30.8%) children died, while in children with NS and normal
      renal functions, CR was obtained in 3(14.2%), partial remission (PR) in
      10(47.6%),CKD in 4(19%), and ESRD in 3 (14.3%).Outcome of cases presenting as
      RPGN was CR in 13 (44.8%), CKD in 2(6.9%) and ESRD in 7(24.1%) cases. Four
      children (13.8%) were lost to follow-up, while 3(10.3%) died. CONCLUSIONS:
      Children with MCGN presenting clinically with NS with impaired renal functions
      have worst outcome.

PMID- 30108387
TI  - Clinical variability of CYP1B1 gene variants in Pakistani primary congenital
      glaucoma families.
AB  - OBJECTIVE: To explore the spectrum of Cytochrome P450 1B1 gene variants and
      genotype-phenotype correlations in families affected with primary congenital
      glaucoma. METHODS: The cross-sectional study was performed at the Department of
      Biotechnology, Lahore College for Women University, Lahore, and the School of
      Biological Sciences, University of the Punjab, Lahore, Pakistan, from February
      2015 to October 2016. Six consanguineous families having individuals affected
      with primary congenital glaucoma were recruited from different hospitals of the
      city. Sanger sequencing of coding exon of Cytochrome P450 1B1 gene was performed
      in order to identify the variants segregating with the disorder. RESULTS: All six
      families had multiple individuals affected with primary congenital glaucoma. Five
      out of six families (83%, 5/6) showed CYP1B1 mutations upon Sanger sequencing.All
      eighteen patients of five families with homozygous Cytochrome P450 1B1 gene
      variants had different degrees of severity of the phenotypes. Clinical evaluation
      of the affected members revealed congenital glaucoma with a severe phenotype of
      corneal oedema, photophobia and corneal scarring. The onset of the phenotype was
      reported to be congenital but the clinical diagnosis was delayed in four cases
      since medical help was not sought by the families till much later. CONCLUSIONS:
      The different degrees of severe phenotypes even in individuals with the same
      Cytochrome P450 1B1 gene mutation suggested the involvement of modifiers in
      reducing or increasing the disease severity.

PMID- 30108388
TI  - Radiographic analysis of the lumbar and sacral region angles in young Turkish
      adults.
AB  - OBJECTIVE: To determine the normal angular ranges of the lateral spinal
      alignments in the lumbar and sacral regions. METHODS: This cross-sectional study
      was conducted at the Kilis State Hospital, Kahramanmaras Sutcu Imam University,
      Kahramanmaras, Turkey, from February to August 2017, and comprised patients aged
      18-27 years who underwent standardised standing lateral lumbar radiography to
      eliminate hip and low back disorders. All radiographs were obtained from the
      hospital database as well as the demographic and contact information of each
      subject. Patients were invited for an interview and physical examination.
      Standard standing lateral radiographs of the lumbar spine were obtained from
      those who had no complaint of back pain and/or lower back problems. Sacro
      horizontal angle, lumbosacral joint angle and sacral inclination angle were
      measured on the radiographic images. SPSS 22 was used to analyse data. RESULTS:
      Of the 150 subjects evaluated, 80(53.33%) were women and 70(46.77) were men.
      There was no statistically significant difference between women and men regarding
      lumbar lordosis angle, sacro-horizontal angle and lumbosacral angle (p>0.05).
      Sacral inclination angle and lower limb length in men were greater than in women
      (p<0.05). A positive correlation was observed between the lumbar lordosis angle,
      sacral inclination angle and sacro-horizontal angle values, while a negative
      correlation with the lumbosacral angle (p<0.05). There was no relationship
      observed between age, weight, height and body mass index, and sacral inclination,
      sacro-horizontal and lumbosacral angle values (p>0.05). Lumbar lordosis angle
      increased depending on the increase of the body mass index (p<0.05). CONCLUSIONS:
      Values identified can be considered as reference values for young healthy Turkish
      adults.

PMID- 30108389
TI  - Frequency of allergic asthma and common aeroallergens sensitization in Pakistani
      patients of bronchial asthma.
AB  - OBJECTIVE: To determine the frequency of allergic asthma and 18common causative
      aeroallergens sensitisation among patients of bronchial asthma. METHODS: This
      descriptive cross-sectional study was conducted at the Armed Forces Institute of
      Pathology, Rawalpindi, Pakistan, from March 2014 to March 2016, and comprised
      clinically-diagnosed adult patients of bronchial asthma referred from various
      hospitals of Rawalpindi and Islamabad. Detailed history of each patient was
      recorded. Serum total immunoglobulin E level was determined using enzyme-linked
      immunosorbent assay. Skin prick test for 18 common aeroallergens was performed.
      SPSS 20 was used for data analysis.. RESULTS: Of the 105 patients, 62 (59.05%)
      were males and 43(40.95%) were females. The overall mean age for males and
      females was 29.9+/-10.2 years and 28.7+/-7.0 years respectively. Overall mean
      serum total immunoglobulin E was 285.01+/-241.39IU/ml. Frequency of
      atopy/allergic asthma was 59(56.2%) and patients with raised total immunoglobulin
      E had more chance of developing allergic asthma than those having normal
      immunoglobulin E(p <0.05). Frequency of allergen sensitisation was the highest
      with house dust mite 35(33.3%), followed by paper mulberry 33(31.4%) and grass
      28(26.7%) cases.s. CONCLUSIONS: Prevalence of allergic asthma was high and the
      most common allergen causing highest sensitisation was house dust mite.

PMID- 30108390
TI  - T cell reactivity to Collagen II as a possible prognostic marker in patients with
      rheumatoid arthritis.
AB  - OBJECTIVE: To compare the frequency and the functional state of the collagen II
      reactive T cells with disease activity in rheumatoid arthritis patients and
      healthy controls. METHODS: This case-control cross-sectional study was carried
      out at the Department of Immunology; Armed Forces Institute of Pathology,
      Rawalpindi, Pakistan, from June to October 2014. Rheumatologist from Rehmat Noor
      Rheumatology Clinic, a private health facility of the city, was requested to send
      in patients with clinical diagnosis of rheumatoid arthritis. Samples were
      obtained and relevant investigations were carried out. Data were compared with a
      group of age and gender-matched healthy subjects. T cell proliferative response
      was assessed against bovine collagen II by measuring incorporation of
      bromodeoxyuridine into deoxyribonucleic acid of proliferating cells and by
      expression of CD25 on proliferating cells as percentage of
      CD3+/bromodeoxyuridine+ and CD3+/CD25+ T-cells, respectively. Among the patients,
      the frequency of T cells with disease activity was compared. Patients were
      classified into groups of mild, moderate and severe disease and frequency of
      CD3+/bromodeoxyuridine+, frequency of CD3+/CD25+ cells, mean fluorescent
      intensity of bromodeoxyuridine-fluorescein isothiocyanate and mean fluorescent
      intensity of CD25-fluorescein isothiocyanate were compared in the groups.
      RESULTS: Of the 60 subjects, 30(50%)were patients and 30(50%) were controls. Of
      the patients, 5(16.66%) were males and 25(83.33%) were females with an overall
      mean age of 42+/-12 years. The mean age of the controls was 41+/-9.28 years. Mean
      disease duration of the patients was 10.5 +/- 4.2 years. Percentage of CD3+/CD25+
      cells and CD3+/bromodeoxyuridine+ cells stimulated with collagen II, in patients
      was much higher than the controls(p<0.05).Statistically significant differences
      were observed when frequency of CD3+/bromodeoxyuridine+ cells and CD3+/CD25+
      cells was compared among the mild, moderate and severe patient groups (p<0.05).
      CONCLUSIONS: Collagen II was found to be an important auto antigen in joints of
      rheumatoid arthritis patients.

PMID- 30108391
TI  - Why do medical students forget anatomy later on? A qualitative study.
AB  - OBJECTIVE: To explore medical students' perceptions of the factors contributing
      to retention of anatomy and its relevance to their clinical practice. METHODS:
      The qualitative study was conducted at Al Nafees Medical College, Islamabad,
      Pakistan, in February 2017, and comprised final year students who appeared in a
      test of anatomy based on multiple choice questions. Six high achievers and six
      low achievers of the test were selected for in-depth one-on-one semi-structured
      interviews. All interviews were audio recorded, transcribed and analysed using
      NVivo software version 11.The reasons why medical students forget anatomy later
      on were found by thematic analysis. RESULTS: Of the final year batch of 100
      students, 64 students volunteered to take the test. A total of 8 themes were
      identified. Some factors were uniformly distributed among the high and low
      achievers, but teaching with clinical context, use of learning strategies,
      teaching core anatomy concepts, and reinforcement was demonstrated more by the
      high achievers. (70%) Majority of low achievers (55%) showed the lack of use of
      metacognitive strategies and strategic learning strategies for retention of
      anatomy. CONCLUSIONS: The factors responsible for retaining anatomy were found to
      be teaching with clinical context, teaching core content of anatomy,
      reinforcement and the integration of anatomy in the clinical years.

PMID- 30108392
TI  - Role of melatonin in management of hypoxic ischaemic encephalopathy in newborns:
      A randomized control trial.
AB  - OBJECTIVE: To find out the effect of melatonin as adjunct therapy on outcome of
      admitted newborns presenting with hypoxic ischaemic encephalopathy. METHODS: This
      randomized controlled trial was conducted at King Edward Medical University,
      Lahore, Pakistan, from October 2016 to March 2017, and comprised newborns with
      gestational age of 34 weeks or higher who fulfilled the definition of hypoxic
      ischaemic encephalopathy and presented within 12 hours of birth. The severity of
      hypoxic ischaemic encephalopathy was assessed by Thompson score. The subjects
      were randomised into standard treatment group and intervention group which
      received melatonin 10mg orally via nasogastric tube at admission. Newborns were
      followed for 28 days to see the effect of melatonin in terms of survival rate.
      Data was analyzed using SPSS 20. RESULTS: There were 80 newborns with overall
      mean gestational age of 36.81+/-1.7 weeks and mean birth weight of 2578.75+/-536
      grams. Each of the two groups had 40(50%) subjects. In the intervention group,
      35(87%) subjects and 26(65%) cases in the standard treatment group survived
      (p=0.03). CONCLUSIONS: Administration of melatonin as an adjunct therapy in the
      management of newborns with hypoxic ischaemic encephalopathy led to improved
      survival rate.

PMID- 30108393
TI  - The effect of personal space on blood pressure in the Turkish woman.
AB  - OBJECTIVE: To explore the effect of personal space on blood pressure using the
      Giger and Davidhizar transcultural assessment model. METHODS: The quasi
      experimental study was carried out in a maternity hospital located in Isparta,
      Turkey, from March to July 2014, and comprised all the women hospitalised in the
      obstetrics and gynaecology clinic. The blood pressure measurements were performed
      by two nursing students; one male and one female. The questionnaire was composed
      by the researchers in reference to the sub-dimensions of the Giger and Davidhizar
      transcultural assessment model. RESULTS: There were 115 women with a mean age of
      26.50+/-4.86 years. Overall, 81(70.4%) patients were members of a nuclear family,
      and 43(37.4%) were primary school graduates. There was no significant difference
      in the diastolic blood pressure values measured by female and male students
      (p>0.05), but systolic blood pressure values measured by the female and male
      students were significantly different (p<0.05).. CONCLUSIONS: Female patients had
      increased systolic blood pressure values when they were measured by male nursing
      students and the increase was correlated with ethnicity and income level.

PMID- 30108394
TI  - Frequency of bacterial contamination in platelet concentrates in a tertiary care
      cardiac hospital in Rawalpindi, Pakistan.
AB  - Bacterial contamination of platelets concentrates (PCs) can result in transfusion
      transmissible infection. Storage temperature for platelets provides favourable
      environment for the bacterial growth. This study was conducted at Rawalpindi
      Institute of Cardiology, Rawalpindi, Pakistan from May, 2016 to July 2016. A
      total of 200 (48 hours stored) whole blood derived PCs collected were selected
      for the study. Sample were inoculated into Oxoid Signal blood culture bottles and
      incubated at 36+/-1 degrees C for 07 days. Signal culture bottle with positive
      signals and visual appearance of turbidity were sub-cultured. Bacterial growth
      identification was carried out by standard reference methods. Out of 200
      platelets concentrates, 63 suspected turbid and 02 with positive signal culture
      device were sub-cultured and identified. Staphylococcus aureus was identified in
      02 bottles. The overall frequency of bacterial contamination in PCs was found to
      be 1%. The frequency of bacterial contamination in PCs found is very high as
      compared to developed counties. There is need of strict adherence to standard
      protocols for the prevention, early detection, and reporting of bacterial
      contamination in the PCs in Pakistan.

PMID- 30108395
TI  - When three emergency physicians flew together.

PMID- 30108396
TI  - Spatial distribution of under five year olds being sick or injured in the past
      two weeks by district in Pakistan.
AB  - Use of GIS to visualize the pattern and distribution of health indices in
      Pakistan would help in better choreographing of health policy and resource
      allocation decisions. In this study, district-wise spatial distribution of under
      five-year old children who got sick or injured in the past two weeks, and health
      consultation pattern was studied using the Pakistan Social and Living Standards
      Survey 2014-2015. Sex, urban/rural residency status, and province-based
      differences in the district-wise distribution of under-five year old children who
      fell sick/injured in the past two weeks and their having received health
      consultation for it, were observed. For male children, southwestern districts of
      Sindh, southeastern districts of Balochistan, central districts of KPK, and one
      southeastern of Punjab reported the highest percent of children who were sick or
      injured in the past two weeks. For females the pattern was similar with few
      exceptions.

PMID- 30108397
TI  - Aorto-caval fistula resulting from an abdominal aortic aneurysm: A case report
      from the Emergency Department of Izmir Bozyaka Training and Research Hospital,
      Turkey.
AB  - The rupture of an abdominal aortic aneurysm into the inferior vena cava with
      fistula formation is a rare condition but is associated with high mortality.
      Classical symptoms and findings vary in a wide range, and early diagnosis and
      intervention can be life-saving. In this study, we present a case of abdominal
      aortic aneurysm associated with aorto-caval fistula formation accompanied by
      mortality.

PMID- 30108398
TI  - Perirenal haemorrhage after successful stent placement in a patient with
      atherosclerotic renal artery stenosis: A case report.
AB  - Atherosclerotic renal artery stenosis is a potentially correctable cause of
      secondary hypertension. Most patients with renal artery stenosis are managed with
      medical therapy alone. However, percutaneous renal angioplasty could be more
      effective than conventional medical therapy in several specific conditions.
      Common complications following renal angioplasty include puncture site haematoma,
      branch vessel occlusion, and renal artery dissection. However, late perirenal
      haemorrhage following the procedure is rarely reported. We report a case of
      perirenal haemorrhage after successful percutaneous renal artery stent placement
      in a patient diagnosed with unilateral atherosclerotic renal artery stenosis.

PMID- 30108399
TI  - Allgrove syndrome: case report of 7 years old boy from Bahawalpur.
AB  - Allgrove syndrome is a rare autosomal recessive syndrome of unknown prevalence.
      The first case of Allgrove syndrome was reported in 1978 by Allgrove. It is
      characterized by triad of achalasia, alacrima and adrenal hypoplasia. There are
      also associated autonomic and neurological manifestations. We report the case of
      a 7 years old boy being treated for achalasia cardia, presented with fits and
      altered sensorium which on further investigations was found to be due to adrenal
      insensitivity (Raised ACTH level, low Cortisol level, and normal Aldosterone and
      Renin ratio). He also had undiagnosed alacrima since birth, mild degree of
      hearing loss and autonomic instability in the form of episodic hypertension.

PMID- 30108400
TI  - Low grade Mullerian adenosarcoma of pouch of Douglas recurring as bilateral
      ovarian high grade Mullerian adenosarcoma with rhabdomyosarcomatous overgrowth
      after 11 years.
AB  - Mullerian adenosarcoma (MA) of ovary with sarcomatous (rhabdomyoblastic)
      overgrowth is an extremely rare malignant type of female genital tract neoplasm.
      These tumours are highly aggressive and presence of heterologous elements is
      associated with worse prognosis. A 44 year old female presented with lower
      abdominal pain and distension. She had history of removal of tumour from pouch of
      Douglas in 2006 for which she did not receive any additional treatment nor did
      she keep continuous follow up. Current preoperative radiological examination
      revealed bilateral ovarian masses. She underwent abdominal hysterectomy with
      bilateral oophorectomy. Microscopic examination revealed biphasic tumours
      exhibiting sarcomatous overgrowth with rhabdomyoblastic differentiation. Review
      of the previous biopsy revealed low grade Mullerian adenosarcoma without
      sarcomatous overgrowth. Hence the current tumour was considered recurrent. This
      report highlights the aggressive nature of MA even with low grade morphological
      features and emphasizes the importance of continuous follow up and additional
      treatment.

PMID- 30108401
TI  - A case of Avascular Necrosis in a patient with Adrenocortical Carcinoma and
      Disseminated Metastasis.
AB  - 28 years old, male patient was diagnosed with Metastatic Adrenocortical Carcinoma
      after extensive investigation. Patient's primary concern was only his right hip
      and right shoulder pain. On imaging investigations, the patient was diagnosed
      with Avascular Necrosis of the right hip joint. Further laboratory work-up for
      avascular necrosis showed Primary Hypercortisolism and eventually patient was
      found to have Adrenocortical Carcinoma base on CT and bone scan results,
      Avascular Necrosis usually presents with pain in the affected area, mostly
      involving shoulder, knee or hip joint. Among many of the causes of Avascular
      necrosis, one rare cause is hormone secreting Adreno cortical Carcinoma, a rare
      and a highly malignant tumour. Patients can present with Cushing's syndrome or
      can have atypical presentation like this patient. This patient did not have any
      symptoms related to malignancy such as loss of appetite and weight loss.

PMID- 30108402
TI  - Paediatric insulin injection technique: The softer side.
AB  - This communication highlights the unique features of insulin injection technique
      in the paediatric age group. It describes the anatomical, neurodevelopmental and
      psychosocial characteristics of children and adolescents of various age groups.
      These are correlated to highlight 'best practices' or 'injection manner' which
      diabetes care providers and care givers should observe, in order to achieve a
      'happy' and healthy insulin injection experience for the child. The softer side
      of paediatric insulin injection technique adds to existing guidelines on insulin
      delivery. It encourages research on the special needs and challenges of children
      and adolescents living with diabetes.

PMID- 30108403
TI  - Biological characteristics and outcomes of Gliosarcoma.
AB  - Gliosarcoma is a highly aggressive primary brain tumour. It is a relatively rare
      tumour and comprises of two histological components, glial and sarcomatous.
      Gliosarcomas carry a poorer prognosis than that of Glioblastoma Multiforme (GBM).
      The current review highlights important histological and radiological features of
      gliosarcoma in the light of recent literature, and also touches upon the
      treatment options and outcomes of various types of gliosarcoma.

PMID- 30108404
TI  - Physiological Uptake of F18-FDG in breast parenchyma.
AB  - Increased F18-FDG uptake is on PET-CT images should always be assessed carefully
      for physiological and pathological causes. Breast uptake may be focal or diffuse.
      Although propensity of tumours increase in focal uptake; diffuse involvement may
      be seen in lymphoma and some types of breast cancer. Frequently, diffuse breast
      uptake is non-pathologic due to infection, physiological uptake or lactation. We
      describe the case of a 27-years old female who underwent 18F FDGPET-CT scan for
      staging workup of diffuse large B-cell lymphoma (DLBCL). The scan demonstrated
      bilateral F18-FDG breast uptake, due to ongoing lactation.

PMID- 30108406
TI  - Response to Comments on Suhail Anwar (J Pak Med Assoc. 68: 692-693, 2018) The
      role of a cancer registry in a health-care system.

PMID- 30108405
TI  - Comments on Suhail Anwar (J Pak Med Assoc. 68: 692-693, 2018) The role of a
      cancer registry in a health-care system.

PMID- 30108407
TI  - Student's opinion regarding teaching methods: A survey amongst MBBS and BDS
      students of a private Medical University in Karachi - Short Communication.
AB  - A cross sectional study was conducted in a private medical university among
      undergraduate MBBS and BDS students, to ascertain their opinion regarding various
      teaching methods. Convenience sampling technique was utilized with data
      collection spanning over March to August 2015 on a sample of 398 students. A self
      administered questionnaire was used for the purpose. Descriptive analysis was
      applied for numerical data while chi square was used for categorical data. P
      value under 0.05 was considered significant. Our results showed that around 120
      (30%) of the participants supported PBL as the most effective teaching method
      while 64(16%) considered clinical rotations, and 60(15%) voted for lectures.
      According to undergraduate students Problem-based Learning is the most
      significant tool for learning. Integrated method of teaching was endorsed by both
      MBBS and BDS students.

PMID- 30108409
TI  - Groundwater contamination and the risk of arsenic poisoning in Pakistan.

PMID- 30108408
TI  - Penetrating cardiac trauma: A retrospective case series from Karachi.
AB  - Penetrating cardiac trauma is a medical emergency that commonly affects young men
      throughout the world. A retrospective review of the records of all patients
      presenting with cardiac injury was done from January 2000 to December 2015 at our
      institute. There were 10 cases of such trauma, all of whom were males, 17 to 48
      years of age. The most common mechanism of injury was gunshot wounds followed by
      stab wounds. The Mean Revised Trauma Score was 7.23+/-0.855. Only 2 out of the
      total 10 patients died (20% mortality). The Right Ventricle followed by the Left
      Ventricle was the most common site of injury. Median Sternotomy was the surgical
      procedure of choice in managing these patients. Pericardial tamponade and
      Haemothorax were common intra-operative findings. Patients having penetrating
      cardiac injury presenting with detectable signs of life on arrival to the
      hospital can be rescued by early surgical intervention.

PMID- 30108410
TI  - A void yet to fill the lack of effective patient counseling.

PMID- 30108411
TI  - Chikungunya virus: Reared its head in Karachi-Pakistan.

PMID- 30108413
TI  - Design of peptide epitope from the neuraminidase protein of influenza A and
      influenza B towards short peptide vaccine development.
AB  - Influenza viruses A and B are important human respiratory pathogens causing
      seasonal, endemic and pandemic infections in several parts of the globe with high
      morbidity and considerable mortality. The current inactivated and live attenuated
      vaccines are not effective. Therefore, it is of interest to design universal
      influenza virus vaccines with high efficacy. The peptide GQSVVSVKLAGNSSL of
      pandemic influenza, the peptide DKTSVTLAGNSSLCS of seasonal influenza and the
      peptide DILLKFSPTEITAPT of influenza B were identified as potential linear cell
      mediated epitopes. The epitopes predicted by BepiPred (B-cell epitope designer)
      program was subjected to docking experiment-using HexDock and CABS dock programs.
      The epitopes of pandemic H1N1 influenza A gave similar score of high affinity in
      docking. The epitope DKTSVTLAGNSSLCS of seasonal influenza A and epitope
      DILLKFSPTEITAPT of influenza B had high binding energy. It is further observed
      that the peptides GQSVVSVKLAGNSSL (pandemic influenza), DKTSVTLAGNSSLCS (seasonal
      influenza) DILLKFSPTEITAPT (influenza B) are found to interact with some known
      MHC class II alleles. These peptides have high-affinity binding with known MHC
      class II alleles. Thus, they have the potential to elicit cell immune response.
      These vaccines have to be further evaluated in animal models and human
      volunteers. These findings have application in the development of peptide B-cell
      epitope vaccines against influenza viruses.

PMID- 30108414
TI  - PROPAB: Computation of Propensities and Other Properties from Segments of 3D
      structure of Proteins.
AB  - : Residues in allelic positions, in the local segment of aligned sequences of
      proteins show wide variations. Here, we describe PROPAB that computes the
      propensity tables for helix, strand and coil types from multiple 3D structure
      files following ab initio statistical procedure. It also classifies them in range
      specific and chain specific manners. It further computes percentage composition
      and physicochemical properties along with residues propensities. It also prepares
      FASTA files for different segments (helix, strand and coil) in the exact order
      that they follow in the sequence. Representative analyses on orthologous
      (homologous across species) proteins demonstrate wide segmental variations of
      physicochemical properties. Such variations provide insights to relate the
      adaptation of these proteins in a given functional constraint under diverse
      environmental conditions. Thus, the program finds applications in the structural
      and evolutionary analysis of proteins. Availability: PROPAB is freely available
      at http://sourceforge.net/projects/propab/for worldwide user.

PMID- 30108416
TI  - Future Innovations in Viral Immune Surveillance: A Novel Place for Bioinformation
      and Artificial Intelligence in the Administration of Health Care.
AB  - Novel developments in bioinformation, bioinformatics and biostatistics, including
      artificial intelligence (AI), play a timely and critical role in translational
      care. Case in point, the extent to which viral immune surveillance is regulated
      by immune cells and soluble factors, and by non-immune factors informs the
      administration of health care. The events by which health is regained following
      viral infection is an allostatic process, which can be modeled using Hilbert's
      and Volterra's mathematical biology criteria, and biostatistical methodologies
      such as linear multiple regression. Health regained following viral infection can
      be given as Y being the sum-total of the positive factors and events (?) that
      inherently push allostasis forward (i.e., the orderly process of immune
      activation and maturation) and the negative (N) factors and events that,
      allostatically speaking, interfere with regaining health. Any gaps in knowledge
      are filled by AI-aided immune tweening. Proof of concept can be tested with the
      fast-gaining infection using tick-borne Bunyavirus that cause severe fever with
      thrombocytopenia syndrome (SFTS).

PMID- 30108415
TI  - Insights from the sequence similarity of Zika virus proteins with the Human nerve
      proteins.
AB  - Massive peptide sharing between the Zika virus polyprotein and host tissue
      proteins could elicit significant host-pathogen interactions and cross-reactions
      leading to autoimmune diseases. This study found similarities in the Zika V
      proteins and human nerve tissue proteins. 63 human nerve proteins were screened
      for similarities with the Zika V of which Neuromodulin, Nestin, Galanin,
      Bombesin, Calcium-binding protein were found to have similarities to the Zika V
      poly protein C at different sequence regions. These sequence similarities could
      be significant in regulating pathogenic interactions/autoimmunity, as Polyprotein
      C is known to be a virulent factor.

PMID- 30108412
TI  - Taxonomy of Aspergillus section Flavi and their production of aflatoxins,
      ochratoxins and other mycotoxins.
AB  - Aflatoxins and ochratoxins are among the most important mycotoxins of all and
      producers of both types of mycotoxins are present in Aspergillus section Flavi,
      albeit never in the same species. Some of the most efficient producers of
      aflatoxins and ochratoxins have not been described yet. Using a polyphasic
      approach combining phenotype, physiology, sequence and extrolite data, we
      describe here eight new species in section Flavi. Phylogenetically, section Flavi
      is split in eight clades and the section currently contains 33 species. Two
      species only produce aflatoxin B1 and B2 (A. pseudotamarii and A. togoensis), and
      14 species are able to produce aflatoxin B1, B2, G1 and G2: three newly described
      species A. aflatoxiformans, A. austwickii and A. cerealis in addition to A.
      arachidicola, A. minisclerotigenes, A. mottae, A. luteovirescens (formerly A.
      bombycis), A. nomius, A. novoparasiticus, A. parasiticus, A. pseudocaelatus, A.
      pseudonomius, A. sergii and A. transmontanensis. It is generally accepted that A.
      flavus is unable to produce type G aflatoxins, but here we report on Korean
      strains that also produce aflatoxin G1 and G2. One strain of A. bertholletius can
      produce the immediate aflatoxin precursor 3-O-methylsterigmatocystin, and one
      strain of Aspergillus sojae and two strains of Aspergillus alliaceus produced
      versicolorins. Strains of the domesticated forms of A. flavus and A. parasiticus,
      A. oryzae and A. sojae, respectively, lost their ability to produce aflatoxins,
      and from the remaining phylogenetically closely related species (belonging to the
      A. flavus-, A. tamarii-, A. bertholletius- and A. nomius-clades), only A.
      caelatus, A. subflavus and A. tamarii are unable to produce aflatoxins. With
      exception of A. togoensis in the A. coremiiformis-clade, all species in the
      phylogenetically more distant clades (A. alliaceus-, A. coremiiformis-, A.
      leporis- and A. avenaceus-clade) are unable to produce aflatoxins. Three out of
      the four species in the A. alliaceus-clade can produce the mycotoxin ochratoxin
      A: A. alliaceus s. str. and two new species described here as A. neoalliaceus and
      A. vandermerwei. Eight species produced the mycotoxin tenuazonic acid: A.
      bertholletius, A. caelatus, A. luteovirescens, A. nomius, A. pseudocaelatus, A.
      pseudonomius, A. pseudotamarii and A. tamarii while the related mycotoxin
      cyclopiazonic acid was produced by 13 species: A. aflatoxiformans, A. austwickii,
      A. bertholletius, A. cerealis, A. flavus, A. minisclerotigenes, A. mottae, A.
      oryzae, A. pipericola, A. pseudocaelatus, A. pseudotamarii, A. sergii and A.
      tamarii. Furthermore, A. hancockii produced speradine A, a compound related to
      cyclopiazonic acid. Selected A. aflatoxiformans, A. austwickii, A. cerealis, A.
      flavus, A. minisclerotigenes, A. pipericola and A. sergii strains produced small
      sclerotia containing the mycotoxin aflatrem. Kojic acid has been found in all
      species in section Flavi, except A. avenaceus and A. coremiiformis. Only six
      species in the section did not produce any known mycotoxins: A. aspearensis, A.
      coremiiformis, A. lanosus, A. leporis, A. sojae and A. subflavus. An overview of
      other small molecule extrolites produced in Aspergillus section Flavi is given.

PMID- 30108417
TI  - Structure modeling to function prediction of Uncharacterized Human Protein
      C15orf41.
AB  - The dyserythropoietic anemia disease is a genetic disorder of erythropoiesis
      characterized by morphological abnormalities of erythroblasts. This is caused by
      human gene C15orf41 mutation. The uncharacterized C15orf41 protein is involved in
      the formation of a functional complex structure. The uncharacterized C15orf41
      protein is thermostable, unstable and acidic. This is associated with TPD
      (Treponema Pallidum) domain (135 to 265 residue position) and three PTM sites
      such as K50 (Acetylation), T114 (Phosphorylation) and K176 (Ubiquitination).
      C15orf41 is paralogous to isoform-1 (gi|194018542|) and open reading frame
      isoform-CRA_c (gi|119612744|) of Homo sapiens located at chromosome 15. It
      interacts with the human ATP (Adenosine Triphosphate) binding domain 4 (ATPBD4)
      having similarity score 0.725 as per protein-protein interaction (PPI) network
      analysis. This data provides valuable insights towards the functional
      characterization of human gene C15orf41.

PMID- 30108418
TI  - Prediction of Protein Acetylation Sites using Kernel Naive Bayes Classifier Based
      on Protein Sequences Profiling.
AB  - Lysine acetylation is one of the decisive categories of protein post
      translational modification (PTM), it is convoluted in many significant cellular
      developments and severe diseases in the biological system. The experimental
      identification of protein-acetylated sites is painstaking, time-consuming and
      expensive. Hence, there is significant interest in the development of
      computational approaches for consistent prediction of acetylation sites using
      protein sequences. Features selection from protein sequences plays a significant
      role for acetylation sites prediction. We describe an improved feature selection
      approach for acetylation sites prediction based on kernel naive Bayes classifier
      (KNBC). We have shown that KNBC generated from selected features by a new feature
      selection method outperforms than the existing methods for identification of
      acetylation sites. The sensitivity, specificity, ACC (Accuracy), MCC (Matthews
      Correlation Coefficient) and AUC (Area under Curve of ROC) in our proposed method
      are as follows 80.71%, 93.39%, 76.73%, 41.37% and 83.0% with the optimum window
      size is 47. Thus the kernel naive Bayes classifier finds application in
      acetylation site prediction.

PMID- 30108420
TI  - Molecular Docking Analysis of Pyrimethamine Derivatives with Plasmodium
      falciparum Dihydrofolate Reductase.
AB  - DHFR from Pf is a known target for malaria. There is a continued effort for the
      design and development of the potent inhibitor for PfDHFR in the control of
      malaria. Therefore it is of interest to screen PfDHFR with the derivatives of
      Pyrimethamine. The results show that the compound CID 10476801 has lowest docked
      energy (-11.48 kcal/mol) with protein likely to be a drug candidate, probably
      inhibiting PfDHFR structure. Residues of PfDHFR protein involved in the formation
      of hydrogen bonds with compound CID 10476801 are confirmed to be ASP54. The
      findings provide new insights into development of potent chemotherapeutic drug
      for combating malaria.

PMID- 30108419
TI  - Insights from the Molecular modeling, docking analysis of illicit drugs and Bomb
      Compounds with Honey Bee Odorant Binding Proteins (OBPs).
AB  - Analysis of honeybee PBPs is of interest in the development of Biosensor
      applications. We described the predicted binding of 19 such compounds with 43
      honey bee OBPs using molecular modeling, docking and phylogenetic analysis.
      Therefore, training the honeybees using preferred compounds formulate the bees to
      identify the illicit drugs and bomb compounds. Consequently, high docking score
      produced complex such OBP16-N-Phenyl-2-Napthalamine (-12.25k/mol), 3BJH-Crack
      Cocaine (-11.75k/mol), OBP10-Methadone (- 11.71k/mol), 1TUJ-Dronobinal Cannabis (
      11.66k/mol), OBP13-Plasticizer (-11.27k/mol) and OBP24-Ecstasy (-10.89 k/mol) can
      be used to identify the compounds using biosensor application. The chemical
      reaction of the compounds for olfactory sensory was analyzed using DFT (Density
      Functional Theory) studies. Some of these compounds show high binding OBPs across
      distant phylogeny.

PMID- 30108421
TI  - Comparative evaluation of anti-angiogenic effects of noscapine derivatives.
AB  - Angiogenesis, the formation of new capillaries from pre-existing vessels, is
      essential for tumor progression. Synthetic derivatives of anti-cancer compound,
      noscapine (an opium alkaloid) such as Cl-noscapine, Br-noscapine and Folate
      noscapine along with two of the reference compounds, TNP-470 and paclitaxel were
      examined for anti-angiogenic activities by using human umbilical vein endothelial
      cells (HUVECs). The noscapine derivatives showed anti-angiogenic activity albeit
      at high concentration compared to the reference compounds. All the tested
      compounds inhibited angiogenesis in a dose-dependent manner; the drug
      concentration causing 50% inhibition of cell survival was 11.87 MUM for Cl
      noscapine, 6.9 MUM for Br-noscapine and 6.79 MUM for folate-noscapine. Besides,
      all the noscapine derivatives significantly inhibited cord formation (IC50 for Cl
      noscapine is 50.76 MUM, for Br-noscapine is 90.08 MUM and for folate-noscapine is
      18.44 MUM) as well as migration and invasion (IC50 value of Cl-noscapine is 28.01
      MUM, for Br-noscapine is 19.78 MUM and for folate-noscapine is 10.76 MUM) of
      endothelial cells. Based on these results, we speculated that the inhibitory
      effects on human endothelial cell proliferation of noscapine derivatives might be
      important for anti-angiogenesis.

PMID- 30108422
TI  - Selection of Luteolin as a potential antagonist from molecular docking analysis
      of EGFR mutant.
AB  - The life-threatening sides effect of the current EGFR mutant inhibitors (drugs)
      such as the eruption of rash which can be seen on the face, chest, back and even
      the trunk, diarrhea, nausea, vomiting, anorexia and stomatitis, necessitates the
      discovery of new potent and safe compounds as a chemo-therapeutic measure against
      lung cancer. Approximately about 10% of patients with Non-small cell lung cancer
      (NSCLC) in the US and about 35% in East Asia have tumor associated EGFR. These
      mutations occur within EGFR exon 18-21, which encodes a portion of the EGFR
      kinase domain and enables researchers to identify compounds that only recognizes
      and binds to the cancer cells. Thus, mutations in EGFR play a role as both
      biomarkers and rational targets for targeted therapy. In view of this, we out
      source for the best-in -class inhibitor for this druggable target via
      computational tools. The purpose of this study was to analyze the inhibitory
      potential of luteolin by computational docking studies. For this, three (3)
      flavone chemical compounds (phytochemicals) retrieved from literatures were
      screened for their inhibitory effects on the epidermal growth factor receptor
      (EGFR). Luteolin was the lead compound with a binding energy of -7.7 kcal/mol.
      Computational docking analysis was performed using PyRx, AutoDock Vina option
      based on scoring functions and the target was validated so as to ensure that the
      right target and appropriate docking protocol was used for this analysis.

PMID- 30108423
TI  - Study on Regulation of Low Density Lipoprotein Cholesterol Metabolism using PCSK9
      Gene Silencing: A computational Approach.
AB  - Combating and preventing abnormality in lipid metabolism becomes a pivotal
      criterion for research. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is
      a circulating protein; it promotes the degradation of low-density lipoprotein
      receptors (LDL-R) and hence increases LDL-C levels. Silencing the gene PCSK9 at
      post-transcriptional level with the help of small interfering Ribo nucleic acid
      (siRNA) gives a new insight and a novel therapeutic way to regulate LDL-C
      metabolism. Designing and selecting an efficient siRNA for silencing PCSK9 at
      post transcriptional level through computational approach. We have designed three
      siRNAs to silence each mRNA of PCSK9 through computational analysis using
      software Invivogen. Their minimum free energy of hybridization along with their
      secondary structure was obtained using bioinformatics tool BIBISERV2-RNAHYBRID.
      Further factors like GC content, structural linearity and h-b index of mRNA-siRNA
      complex was calculated to assess their knockdown efficiency. The minimum free
      energy of hybridization of the three designed siRNA1, siRNA2 and siRNA3 for
      target mRNA is as follows -27.1kcal/mol, -25.7kcal/mol and - 28.8 kcal/mol.
      siRNA1 having the least minimum free energy of hybridization i.e. -27.1 kcal/mol
      are predicted to be the most efficient towards the PCSK9 gene silencing.

PMID- 30108424
TI  - Polymorphism studies on microRNA targetome of thalassemia.
AB  - Thalassemia is one of the most prevalent hemoglobin disorders. It is caused by
      the decreased or absent synthesis of one globin chain that leads to moderate to
      severe hemolytic anemia in clinical complications. Some genetic factors cause
      these phenotypic variations by the alteration of gene expression. MicroRNAs
      (miRNAs) are post-transcriptional regulators in gene expression. Therefore,
      variations in 3'-untranslated region (3'-UTR) of target genes may affect gene
      expression. It is of interest to evaluate the impact of noncoding SNPs in
      thalassemia related genes on miRNA: mRNA interactions in the severity of
      thalassemia. Polymorphisms that alter miRNA: mRNA interactions were predicted
      using PolymiRTS and Mirsnpscore tools. Then, the effect of predicted target SNPs
      on thermodynamic stability, local RNA structure and regulatory elements was
      investigated using RNAhybrid, RNAsnp and RegulomeDB, respectively. The molecular
      functions and the Biological process of candidate genes were extracted and
      interaction network was created. Forty-six SNPs were predicted to affect 188
      miRNA interactions. These results suggest that 3'-UTR SNP may affect gene
      expression and cause phenotypic variation in thalassemia patients.

PMID- 30108425
TI  - Detection of severity in Alzheimer's disease (AD) using computational modeling.
AB  - The prevalent cause of dementia - Alzheimer's disease (AD) is characterized by an
      early cholinergic deficit that is in part responsible for the cognitive deficits
      (especially memory and attention defects). Prolonged AD leads to moderate-to
      severe AD, which is one of the leading causes of death. Placebo-controlled,
      randomized clinical trials have shown significant effects of Acetyl cholin
      esterase inhibitors (ChEIs) on function, cognition, activities of daily living
      (ADL) and behavioral symptoms in patients. Studies have shown comparable effects
      for ChEIs in patients with moderate-to-severe or mild AD. Setting a fixed
      measurement (e.g. a Mini-Mental State Examination score, as a 'when to stop
      treatment limit) for the disease is not clinically rational. Detection of changed
      regional cerebral blood flow in mild cognitive impairment and early AD by
      perfusion-weighted magnetic resonance imaging has been a challenge. The utility
      of perfusion-weighted magnetic resonance imaging (PW-MRI) for detecting changes
      in regional cerebral blood flow (rCBF) in patients with mild cognitive impairment
      (MCI) and early AD was evaluated. We describe a computer aided prediction model
      to determine the severity of AD using known data in literature. We designed an
      automated system for the determination of AD severity. It is used to predict the
      clinical cases and conditions with disagreements from specialist. The model
      described is useful in clinical practice to validate diagnosis.

PMID- 30108427
TI  - First survey of Interstitial molluscs from Cayo Nuevo, Campeche Bank, Gulf of
      Mexico.
AB  - Six sediment samples weighing between 224-735 g were collected in June of 2016
      from Cayo Nuevo reef, located at the Campeche Bank, southern Gulf of Mexico.
      Samples were collected by SCUBA diving, from were two stations at depths of 7.6
      and 18.2 m. Sediment was sieved and molluscs (adults and micromolluscs <= 10 mm)
      were sorted, examined, and identified to the lowest taxonomic level. A total of
      1,347 specimens was found, of which 224 shells were dead and 1,123 were alive.
      Thirty-four families, 53 genera, and 67 species were identified. The most
      abundant families were Chamidae and Arcidae for the Bivalvia class, and Caecidae
      and Tornidae for the Gastropoda class. The vertical range of Bentharca sp. was
      extended.

PMID- 30108426
TI  - Updates on transcatheter aortic valve replacement: Techniques, complications,
      outcome, and prognosis.
AB  - Transcatheter aortic valve replacement (TAVR) initially emerged as a therapeutic
      option for high-risk patients with severe aortic stenosis. Advancement in
      technologies since the first era of TAVRs, experience from previous obstacles,
      and lessons learned from complications have allowed the evolution of this
      procedure to the current state. This review focuses on the updates on the most
      current devices, complications, and outcomes of TAVR.

PMID- 30108428
TI  - First report of Trichogrammadanausicida and Trichogrammacacaeciae reared from
      Thaumatotibialeucotreta eggs in Israel.
AB  - The egg parasitpoids Trichogrammadanausicida (Nagaraja) and Trichogrammacacaeciae
      (Marchal) (Hymenoptera: Trichogrammatidae), are reported for the first time in
      Israel. Moreover, our discovery of T.danausicida is the first report of this
      parasitoid species outside of India. The occurrence of those trichogrammatids was
      first discovered and documented in May 2016 during a survey of egg parasitoids of
      the False codling moth Thaumatotibialeucotreta (Lepidoptera: Tortricidae). The
      field survey was conducted on castor bean fruits (Ricinuscommunis) in the Israeli
      central coastal plain. The identity of the parasitoids was revealed by means of
      sequencing a portion of the cytochrome oxidase I gene (COI) of the studied
      parasitoids.

PMID- 30108429
TI  - Tapping into technology and the biodiversity informatics revolution: updated
      terrestrial mammal list of Angola, with new records from the Okavango Basin.
AB  - Using various sources, including the Global Biodiversity Information Facility
      (GBIF), published literature, recent (2015-2017) collections, as well as bat
      detector and camera trap surveys with opportunistic sightings and live capture in
      the upper Okavango catchment in central Angola, we present an updated mammal
      checklist of 275 species from 15 different orders for Angola (including the
      Cabinda region). Recent surveys (captures and bat detectors) of small mammals
      from the upper Okavango catchment yielded 46 species (33 species of bats, ten
      species of rodents and three species of shrews). One bat (Pipistrellusrusticus,
      rusty pipistrelle); two rodents (Mussetzeri, Setzer's mouse and
      Zelotomyswoosnami, Woosnam's broad-faced mouse) and one shrew (Suncusvarilla,
      lesser dwarf shrew) were captured for the first time, in Angola. While our
      species lists of bats conformed to predicted totals, terrestrial small mammals
      were under sampled, with only 13 species recorded by our trapping survey compared
      to a total of 42 shrew and rodent species expected based on GBIF records for the
      central Angolan highlands. Seven terrestrial small mammal species (one shrew and
      six rodents) are endemic to the central and western Angolan highlands but none of
      these were captured in our survey. The bat detector surveys added three further
      bat species to the country list: Pipistrellushesperidus, Kerivoulaargentata, and
      Mopsmidas. Camera trap surveys and opportunistic sightings in the upper Okavango
      catchment in 2016 yielded a total of 35 species of medium-large mammals, from 17
      families, although all of these had been reported previously in Angola. GBIF
      proved to be an excellent source of biodiversity data for Angolan mammals, most
      importantly for documenting dramatic historical range changes of larger mammals
      such as the sable (Hippotragusnigerniger), Kirk's sable (H.nigerkirkii) and the
      giant sable (H.nigervariani).

PMID- 30108430
TI  - Phylogeny of hydrothermal vent Iphionidae, with the description of a new species
      (Aphroditiformia, Annelida).
AB  - The scale-worm family Iphionidae consists of four genera. Of these, Thermiphione
      has two accepted species, both native to hydrothermal vents in the Pacific Ocean;
      T.fijiensis Miura, 1994 (West Pacific) and T.tufari Hartmann-Schroder, 1992 (East
      Pacific Rise). Iphionella is also known from the Pacific, and has two recognized
      species; Iphionellarisensis Pettibone, 1986 (East Pacific Rise, hydrothermal
      vents) and I.philippinensis Pettibone, 1986 (West Pacific, deep sea). In this
      study, phylogenetic analyses of Iphionidae from various hydrothermal vent systems
      of the Pacific Ocean were conducted utilizing morphology and mitochondrial (COI
      and 16S rRNA) and nuclear (18S and 28S rRNA) genes. The results revealed a new
      iphionid species, described here as Thermiphionerapanuisp. n. The analyses also
      demonstrated the paraphyly of Thermiphione, requiring Iphionellarisensis to be
      referred to the genus, as Thermiphionerisensis (Pettibone, 1986).

PMID- 30108431
TI  - Irisin protects macrophages from oxidized low density lipoprotein-induced
      apoptosis by inhibiting the endoplasmic reticulum stress pathway.
AB  - Irisin is a newly discovered myokine which can relieve metabolic disorders and
      resist atherosclerosis. The effects of irisin on ox-LDL-induced macrophage
      apoptosis and endoplasmic reticulum stress-related pathways were observed in
      vitro. RAW264.7 macrophages were cultured in vitro and pretreated with irisin at
      20, 40 and 80 ng/ml for 30 min, followed by culture with 100 mg/L ox-LDL and 5
      mg/L tunicamycin (TM) for 12 h. The cell viability and apoptosis were detected by
      MTT assay and annexin V-FITC double staining. The nuclear translocation of
      activating transcription factor 6 (ATF6) was detected by immunofluorescence
      assay. Western blot was used to detect the expressions of p-PERK, p-eIF2alpha,
      C/EBP homologous protein (CHOP) and Bcl-2. Irisin reduced lipid accumulation in
      macrophages in a concentration-dependent pattern and significantly inhibited
      apoptosis induced by ox-LDL and TM. Compared with ox-LDL and TM groups, the
      expressions of CHOP, p-PERK and p-eIF2alpha in the irisin group significantly
      decreased, the translocation of ATF6 from cytoplasm to nucleus was significantly
      weakened, and Bcl-2 expression significantly increased. Irisin can alleviate the
      apoptosis of macrophages induced by ox-LDL, which may be achieved by inhibiting
      the PERK/eIF2alpha/CHOP and ATF6/CHOP endoplasmic reticulum stress signaling
      pathways.

PMID- 30108432
TI  - DUSP1 is involved in the progression of small cell carcinoma of the prostate.
AB  - Small cell carcinoma of the prostate (SCCP) is a rare and the most aggressive
      variant of prostate cancer. There is no effective cure or treatment for SCCP.
      Therefore, there is an urgent need for new therapy to improve the prognosis of
      patients with SCCP. DUSP1 is a dual specific phosphatase with an increasingly
      recognized in tumor biology. Altered expression of DUSP1 induced changes in the
      expression of genes involved in various biological pathways, including cell-cell
      signaling and angiogenesis. To understand more about the role of DUSP1 in SCCP,
      we evaluated the biological function and associated regulatory mechanism of
      DUSP1. In this study, DUSP1 was significantly down-regulated in human SCCP
      compared with the non-carcinoma tissues (P < 0.05). Overexpression of DUSP1 was
      found to suppress MAPK signaling and cell proliferation in PC-3 cells.
      Additionally, silencing of DUSP1 enhanced MAPK signaling and PC-3 cell
      proliferation. Moreover, it was observed that DUSP1 blocked the phosphorylation
      of p38 MAPK induced by anisomycin. Taken together, this investigation suggests
      that DUSP1 is involved in the progression of SCCP and may provide a new
      therapeutic target for SCCP treatment.

PMID- 30108433
TI  - MiR-96 enhances cellular proliferation and tumorigenicity of human cervical
      carcinoma cells through PTPN9.
AB  - Up to date, the cervical cancer remains to be one of the leading gynecological
      malignancies worldwide. MicroRNAs (miRNAs) play critical roles in the process of
      tumor initiation and progression. However, miR-96 has rarely been investigated in
      human cervical carcinoma. We aimed to investigate the biological function and
      underlying molecular mechanism of miR-96 in human cervical carcinoma. MiR-96
      levels were determined by qRT-PCR. Protein tyrosine phosphatase, non-receptor
      type 9 (PTPN9) mRNA and protein levels were investigated by qRT-PCR and western
      blotting. The cellular proliferation in cervical cells was monitored by CyQuant
      assay. Soft agar assay was employed to determine the tumorigenicity. 3' UTR
      luciferase assay was used to validate the target gene of miR-96. SPSS was used to
      analyze statistical significance in different treatment. MiR-96 was dramatically
      upregulated in human cervical tumor tissues. Overexpression of miR-96 was found
      to significantly promote the cellular proliferation and tumorigenicity of
      cervical cells. Furthermore, we showed that PTPN9 was a direct target gene of miR
      96 and had opposite effect to those of miR-96 on cervical cells. MiR-96 may
      promote the cellular proliferation and tumorigenicity of cervical cells by
      silencing PTPN9. Our study highlights an importantly regulatory role of miR-96
      and suggests that an appropriate manipulation of miR-96 may be a new treatment of
      human cervical carcinoma in the future.

PMID- 30108434
TI  - Mycoflora isolation and molecular characterization of Aspergillus and Fusarium
      species in Tunisian cereals.
AB  - Wheat, barley and maize are the mainly consumed cereals in Tunisia. This study
      aimed to determine the mycoflora of these cereals with special focus on the
      mycotoxigenic Aspergillus and Fusarium species. Freshly harvested samples and
      other stored samples of each type of cereal (31 and 34 samples, respectively)
      were collected in Tunisia and cultured for fungal isolation and identification.
      Identification of fungal genera was based on morphological features. Aspergillus
      and Fusarium species were identified by species specific PCR assays complemented
      with DNA sequencing. Alternaria (70.83%), Eurotium (62.50%), Aspergillus (54.17%)
      and Penicillium (41.67%) were the most frequent fungi isolated from wheat.
      Penicillium (75%), Aspergillus (70%), Eurotium (65%) and Alternaria (65%) were
      the most frequently recovered genera from barley. The predominant genera in maize
      were Aspergillus (76.19%), Eurotium (42.86%), and Penicillium (38.09%).
      Aspergilllus, Penicillium, Fusarium and Alternaria were detected in both stored
      and freshly harvested grain samples. The frequencies of contamination with
      Aspergillus, Fusarium and Alternaria were higher in freshly harvested samples,
      whereas Penicillium species were more frequent in stored samples. The predominant
      Aspergillus species detected were A. flavus and A. niger. The Fusarium species
      detected were F. equiseti, F. verticillioides, F. nygamai, and F. oxysporum. This
      study suggested the potential risk for Aflatoxins and, to a lesser extent, for
      Ochratoxin A in Tunisian cereals. This is the first survey about mycoflora
      associated with wheat, barley and maize in Tunisia.

PMID- 30108435
TI  - Early-life gut microbiome and cow's milk allergy- a prospective case - control 6
      month follow-up study.
AB  - Increasing evidence suggests that perturbations in the intestinal microbiota in
      early infancy are implicated in the pathogenesis of food allergy (FA); existing
      evidence on the structure and composition of the intestinal microbiota in human
      beings with FA is limited and conflicting. The main object of the study was to
      compare the faecal microbiota between healthy and cow's milk allergy (CMA)
      infants at the baseline immediately after the diagnosis, and to evaluate the
      changes in the faecal microbiota after 6 months of treatment of CMA infants with
      hypoallergenic formula (HF), compared with healthy children fed on standard milk
      formulae. Sixty infants younger than 4 months of age with challenge-proven CMA
      and 60 healthy age-matched children were investigated in this prospective case -
      control follow-up study. Faecal samples were collected at baseline and at 6
      months of follow-up, microbial diversity and composition were characterized by
      high-throughput 16S rRNA sequencing. The average age (+/-SD) of the infants at
      inclusion was 2.9 +/- 1.0 months. Children with CMA have lower gut microbiota
      diversity and an elevated Enterobacteriaceae to Bacteroidaceae (E/B ratio) in
      early infancy compared with healthy children (115.8 vs. 0.8, P = 0.0002). After 6
      months of treatment with HF, CMA infants had a higher Lactobacillaceae (6.3% vs.
      0.5%, P = 0.04) and lower Bifidobacteriaceae (0.3% vs. 8.2%, P = 0.03) and
      Ruminococcaceae (1.5% vs. 10.5%, P = 0.03) abundance compared with control
      children. Conclusion: Low gut microbiota diversity and an elevated E/B ratio in
      early infancy may contribute to the development of FA, including CMA. A strict
      elimination diet may weaken FA by reducing E/B ratio and promoting a gut
      microbiota that would benefit the acquisition of oral tolerance.

PMID- 30108437
TI  - Apatinib for heavily treated patients with non-small cell lung cancer: Report of
      a case series and literature review.
AB  - Although many strategies have been developed for non-small cell lung cancer
      (NSCLC), more secondary and further treatments are needed due to drug resistance
      or tumor recurrence. Apatinib is a novel oral antiangiogenic agent and in this
      study, we aim to investigate the clinical value of apatinib in heavily pretreated
      NSCLC. Here, we reported the characteristics, efficacy and adverse events of
      three patients treated with apatinib (500 mg/day). We also summarized the
      currently available evidence and ongoing clinical trials regarding the use of
      apatinib in NSCLC. Two cases of adenocarcinoma and one case of squamous cell
      carcinoma were treated with apatinib due to disease progression after previous
      treatments of chemotherapy and epidermal growth factor receptor-tyrosine kinase
      inhibitor (EGFR-TKI). All patients responded to apatinib rapidly and underwent
      drug resistance shortly afterwards. The patient with squamous cell carcinoma died
      of hemoptysis. Other adverse events were acceptable. All previous relevant
      studies were compared and showed similar results but a longer progression-free
      survival. Additionally, ongoing clinical trials were systematically searched and
      listed. In conclusion, apatinib shows some efficacy in heavily treated NSCLC and
      generally tolerable toxicity in non-squamous NSCLC. More solid evidence will be
      accessible in near future.

PMID- 30108436
TI  - Autosomal single-gene disorders involved in human infertility.
AB  - Human infertility, defined as the inability to conceive after 1 year of
      unprotected intercourse, is a healthcare problem that has a worldwide impact.
      Genetic causes of human infertility are manifold. In addition to the chromosomal
      aneuploidies and rearrangements, single-gene defects can interfere with human
      fertility. This paper provides a review of the most common autosomal recessive
      and autosomal dominant single-gene disorders involved in human infertility. The
      genes reviewed are CFTR, SPATA16, AURKC, CATSPER1, GNRHR, MTHFR, SYCP3, SOX9, WT1
      and NR5A1 genes. These genes may be expressed throughout the hypothalamic
      pituitary-gonadal-outflow tract axis, and the phenotype of affected individuals
      varies considerably from varying degrees of spermatogenic dysfunction leading to
      various degrees of reduced sperm parameters, through hypogonadotropic
      hypogonadism reslting in pubertal deficiencies, until gonadal dysgenesis and XY
      and XX sex reversal. Furthermore, congenital bilateral absence of the vas
      deferens, as well as premature ovarian failure, have been reported to be
      associated with some single-gene defects.

PMID- 30108438
TI  - Co-ABC: Correlation artificial bee colony algorithm for biomarker gene discovery
      using gene expression profile.
AB  - In this paper, we propose a new hybrid method based on Correlation-based feature
      selection method and Artificial Bee Colony algorithm,namely Co-ABC to select a
      small number of relevant genes for accurate classification of gene expression
      profile. The Co-ABC consists of three stages which are fully cooperated: The
      first stage aims to filter noisy and redundant genes in high dimensionality
      domains by applying Correlation-based feature Selection (CFS) filter method. In
      the second stage, Artificial Bee Colony (ABC) algorithm is used to select the
      informative and meaningful genes. In the third stage, we adopt a Support Vector
      Machine (SVM) algorithm as classifier using the preselected genes form second
      stage. The overall performance of our proposed Co-ABC algorithm was evaluated
      using six gene expression profile for binary and multi-class cancer datasets. In
      addition, in order to proof the efficiency of our proposed Co-ABC algorithm, we
      compare it with previously known related methods. Two of these methods was re
      implemented for the sake of a fair comparison using the same parameters. These
      two methods are: Co-GA, which is CFS combined with a genetic algorithm GA. The
      second one named Co-PSO, which is CFS combined with a particle swarm optimization
      algorithm PSO. The experimental results shows that the proposed Co-ABC algorithm
      acquire the accurate classification performance using small number of predictive
      genes. This proofs that Co-ABC is a efficient approach for biomarker gene
      discovery using cancer gene expression profile.

PMID- 30108439
TI  - Overexpression of leucine-rich repeat-containing G protein-coupled receptor 5
      predicts poor prognosis in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most common malignancies and the
      fifth leading cause of cancer-related death worldwide. Novel prognostic
      biomarkers are urgently needed for patients with HCC. Leucine-rich repeat
      containing G-protein coupled receptor 5 (LGR5) overexpression may promote tumor
      metastasis in HCC. However, few studies investigate the prognosis predictive role
      of LGR5 in patients with HCC. Herein, we aimed to examine the expression level of
      LGR5 in tumors and its correlation with clinical characteristics and survivals of
      patients with HCC. LGR5 expression in tumor specimens and adjacent tissue
      resected from 66 patients were detected by immunohistochemistry. The results
      showed that the expression of LGR5 was markedly higher in HCC than in normal
      adjacent tissues (P = .006). High expression of LGR5 was significantly correlated
      with later disease stage (P = .009). In addition, high LGR5 expression was
      remarkably correlated with short overall survival than those with low LGR5
      expression (P < .05). The median overall survival of patients with high LGR5
      expression was 12 months, whereas that of patients with low LGR5 expression was
      still not reached (longer than 70 months). Notably, in our limited cases, we did
      not detect any difference in tumor size, lymphatic invasion, or metastasis in
      patients with high or low expression of LGR5. In conclusion, high protein level
      of LGR5 was associated with poor prognosis of these patients. LGR5 appears to be
      a valuable prognostic predictor clinically and a potential target in HCC therapy.

PMID- 30108440
TI  - Lobaplatin-based regimens outperform cisplatin for metastatic breast cancer after
      anthracyclines and taxanes treatment.
AB  - The goal of this study was to assess the antitumor efficacy and safety of
      lobaplatin-based regimens as the second line of treatment in patients with
      metastatic breast cancer (MBC) resistant to anthracyclines and taxanes, compared
      with that of cisplatin-based regimens. During August 2012 to April 2015, 87
      patients who received lobaplatin-based regimens or cisplatin-based regimens were
      included. Medical records of the patients noted that lobaplatin (30 mg/m2) or
      cisplatin (25 mg/m2), combined with another chemotherapeutic agent such as
      Gemcitabine (1000 mg/m2) or Vinorelbine (25 mg/m2), was intravenously given to
      the patients on a basis of twenty-one days as one treatment cycle. All the
      patients were followed until August 2017. The endpoint of this study was
      progression-free survival (PFS), overall survival (OS), and estimated objective
      response rate (RR). Safety and drug tolerability data were also obtained.
      Lobaplatin-based regimens prolonged PFS compared to cisplatin-based regimens
      (median 13.2 vs 4.7 months, hazard ratio = 0.37, 95% confidence intervals: 0.21
      0.67, P = .0007), while OS was not significantly different between the two groups
      (hazard ratio = 0.72, 95% confidence intervals: 0.40-1.30, P = .2767), as was
      objective RR (37.8% vs 33.4%, x2 = 0.19, P = .6653). Nausea/vomiting and renal
      injury were more frequent with cisplatin-based regimens. Our results show that
      lobaplatin-based regimens are superior to cisplatin in terms of efficacy and are
      better tolerated.

PMID- 30108441
TI  - Functional mechanism of Ginsenosides on tumor growth and metastasis.
AB  - Ginsengs, has long been used as one medicinal herb in China for more than two
      thousand years. Many studies have shown that ginsengs have preventive and
      therapeutic roles for cancer, and play a good complementary role in cancer
      treatment. Ginsenosides, as most important constituents of ginseng, have been
      extensively investigated and emphasized in cancer chemoprevention and
      therapeutics. However, the functional mechanism of Ginsenosides on cancer is not
      well known. This review will focus on introducing the functional mechanisms of
      ginsenosides and their metabolites, which regulate signaling pathways related
      with tumor growth and metastasis. Ginsenosides inhibit tumor growth via
      upregulating tumor apoptosis, inducing tumor cell differentiation and targeting
      cancer stem cells. In addition, Ginsenosides regulate tumor microenvironment via
      suppressing tumor angiogenesis-related proteins and pathways. Structural
      modification of ginsenosides and their administration alone or combinations with
      other Chinese medicines or chemical medicines have recently been developed to be
      a new therapeutic strategy for cancer.

PMID- 30108443
TI  - Molecular characterization of antibiotic resistant Escherichia coli isolates
      recovered from food samples and outpatient Clinics, KSA.
AB  - Multidrug-resistant Escherichia coli is one of the most important public health
      concern worldwide that can be transferred through the food of animal origin to
      human being causing serious infection. The genetic responsibility of such
      resistant genes (Plasmids, integrons, and transposons) can be easily transmitted
      from the resistant strain to another. Therefore, the main objectives of the study
      is the molecular characterization of the resistant Escherichia coli isolates
      recovered from food samples and human isolates collected from outpatient clinics,
      KSA especially the resistance strains against aminoglycoside resistance genes
      which are responsible for the resistance against gentamicin and the resistance
      caused beta-lactamases genes. Examination of food samples revealed 120
      Escherichia coli isolates (22.22%) (30 strains O26: K60, 28 strains O128: K67, 20
      strains O111: K58, 18 strains O126: K58, 10 strains O55: K59, 9 strains O86: K61
      and 5 strains O157: H7). All the strains were highly resistance to penicillin,
      amoxicillin-clavulanic and erythromycin with a percentage of 100%, while the
      resistance to gentamicin, ampicillin, oxytetracycline, chloramphenicol,
      norfloxacin, trimethoprim, and nalidixic acid were 83%, 75%, 65.3%, 55.8%, 36.5%,
      30.7% and 26.9% respectively. On the other hand, 59.6% of tested strains were
      sensitive to ciprofloxacin. Positive amplification of 896 bp fragments specific
      for aacC2 genes were observed by PCR designated for the detection of the
      aminoglycoside resistance genes. Meanwhile, multiplex PCR designed to detect the
      ampicillin and amoxicillin-clavulanic acid resistant E. coli isolates revealed
      positive amplification of 516 bp fragments specific for BlaTEM gene with all the
      resistant strains to ampicillin and amoxicillin-clavulanic acid. Moreover,
      positive amplification of 392 bp fragments specific for BlaSHV resistant gene
      were observed with (60.52%) of E. coli isolate. While all the tested strains were
      negative for amplification of BlaOXA_1.

PMID- 30108442
TI  - microRNA-1297 involves in the progression of oral squamous cell carcinoma through
      PTEN.
AB  - Background: Oral squamous cell carcinoma (OSCC) oncogenic mechanisms still remain
      elusive. Herein, we proposed to understand the biological role of a newly
      discovered OSCC miRNA. Methods: MiR-1297 related to OSCC was selected for this
      study. TaqMan qRT- PCR assay was used to profile miRNA and gene expression in 16
      tumors with matched adjacent non-tumor tissues. CCK-8 assay and colony formation
      assay were used to demonstrate cell proliferation. Protein level was determined
      by western blotting. SPSS was used for statistical analyses. Results: MiR-1297 is
      repressed and PTEN activated in OSCC. Moreover, the miR-1297 overexpressing cell
      lines displayed a decrease in cell growth rate. And, suppression of miR-1297
      reversed the cell growth rate. In addition, PTEN silencing display the similar
      pattern as miRNA-1297 overexpression to enhance OSCC cell growth. Conclusions:
      MiRNA and gene expression changes are common event in OSCC. Our results suggest
      miR-1297 may drive tumor progression through PTEN. And, miR-1297 could be a
      promising candidate for future investigation.

PMID- 30108444
TI  - DQB: A novel dynamic quantitive classification model using artificial bee colony
      algorithm with application on gene expression profiles.
AB  - In the medical domain, it is very significant to develop a rule-based
      classification model. This is because it has the ability to produce a
      comprehensible and understandable model that accounts for the predictions.
      Moreover, it is desirable to know not only the classification decisions but also
      what leads to these decisions. In this paper, we propose a novel dynamic
      quantitative rule-based classification model, namely DQB, which integrates
      quantitative association rule mining and the Artificial Bee Colony (ABC)
      algorithm to provide users with more convenience in terms of understandability
      and interpretability via an accurate class quantitative association rule-based
      classifier model. As far as we know, this is the first attempt to apply the ABC
      algorithm in mining for quantitative rule-based classifier models. In addition,
      this is the first attempt to use quantitative rule-based classification models
      for classifying microarray gene expression profiles. Also, in this research we
      developed a new dynamic local search strategy named DLS, which is improved the
      local search for artificial bee colony (ABC) algorithm. The performance of the
      proposed model has been compared with well-known quantitative-based
      classification methods and bio-inspired meta-heuristic classification algorithms,
      using six gene expression profiles for binary and multi-class cancer datasets.
      From the results, it can be concludes that a considerable increase in
      classification accuracy is obtained for the DQB when compared to other available
      algorithms in the literature, and it is able to provide an interpretable model
      for biologists. This confirms the significance of the proposed algorithm in the
      constructing a classifier rule-based model, and accordingly proofs that these
      rules obtain a highly qualified and meaningful knowledge extracted from the
      training set, where all subset of quantitive rules report close to 100%
      classification accuracy with a minimum number of genes. It is remarkable that
      apparently (to the best of our knowledge) several new genes were discovered that
      have not been seen in any past studies. For the applicability demand, based on
      the results acqured from microarray gene expression analysis, we can conclude
      that DQB can be adopted in a different real world applications with some
      modifications.

PMID- 30108445
TI  - MiR-30b-5p modulates glioma cell proliferation by direct targeting MTDH.
AB  - Malignant glioma is the most common and lethal type of primary tumor of the
      central nervous system. The incidence of glioma is increasing year by year. In
      recent years, a variety of new treatment methods have emerged, among which gene
      therapy has become a hotspot. MicroRNAs (miRNAs) are a class of small non-coding
      single-strand RNAs that negatively regulate gene expression at the post
      transcriptional and/or translational level by binding loosely complimentary
      sequences in the 3' untranslated regions (UTRs) of target mRNAs. Several miRNAs
      have been reported to modulate glioma progression. This study aimed to determine
      the function of miR-30b-5p in glioma and its underlying molecular mechanism. miR
      30b-5p expression was significantly lower in gliomas than the normal brain
      tissues. Overexpression of miR-30b-5p was found to significantly inhibit glioma
      cell proliferation in vitro. Further, MTDH expression was significantly higher in
      the gliomas compared with the normal brain tissues. In addition, MTDH was
      validated as direct target of miR-30b-5p. Moreover, cellular proliferation was
      increased after MTDH overexpression in the glioma cells, which reversed the
      effects of miR-30b-5p. Taken together, these results reveal miR-30b-5p impacts
      glioma cell proliferation via direct targeting MTDH and could be a potential
      novel therapeutic target for the treatment of glioma.

PMID- 30108446
TI  - Let-7b contributes to hepatocellular cancer progression through Wnt/beta-catenin
      signaling.
AB  - Elevated evidences show that microRNAs (miRNAs) play vital roles in tumor
      progression regulation. However, the functional role of let-7b in hepatocellular
      carcinoma (HCC) is still largely unknown. In this study, we try to investigate
      the biological activity of let-7b in human HCC cells and try to find the
      potential regulatory signaling pathway. Our results indicate that let- 7b was
      remarkably down-regulated in human HCC tissues by qRT-PCR. In addition, let-7b
      overexpression decreased the expression of beta-catenin and c-Myc, while
      upregulated E-cadherin expression in HCC cells which was verified by quantitative
      real-time PCR (qRT-PCR) and western blotting. Furthermore, Wnt/beta-catenin was
      involved in let-7b biological activity which was revealed by luciferase assay.
      Moreover, Wnt/beta-catenin signaling inhibitor blocks HCC cell proliferation
      which is as the same pattern as let-7b overexpression inhibits in HCC cells
      proliferation. In conclusion, down-regulated let-7b promotes HCC cell
      proliferation through Wnt/beta-catenin signaling in HCC cells. These results
      suggested that appropriate manipulation of let-7b might be a new treatment of
      human HCC in the future.

PMID- 30108448
TI  - Upregulation of miR-582-5p regulates cell proliferation and apoptosis by
      targeting AKT3 in human endometrial carcinoma.
AB  - The human endometrial carcinoma is one of the most common female malignancies,
      and there is an urgent requirement to explore new therapeutic strategies. There
      is accumulating evidence that microRNAs (miRNAs) can serve as potential
      diagnostic and prognostic biomarkers for various types of cancer, but the
      significance of miR-582-5p still remains largely unknown in the endometrial
      carcinoma. The aims of this study were to understand and identify the influence
      of miR-582-5p on the proliferation and apoptosis of human endometrial carcinoma
      and its relevant mechanism. First, quantitative real-time PCR (qRT-PCR) was used
      to detect miR-582-5p and AKT3 expression in human tissue samples and cells. Then,
      CyQuant assay and 2D colony assay were employed to evaluate cell proliferation.
      Western blotting was used to determine protein expression. Subsequently, the
      luciferase reporter assay was used to identify the target of miR-582-5p. Finally,
      Annexin V assay was used to detect cell apoptosis. We found that miR-582-5p
      expression was significantly decreased in human endometrial carcinoma tissues,
      and miR-582-5p upregulation in human endometrial carcinoma cells inhibit cell
      proliferation and promote apoptosis. Moreover, AKT3 was validated as a target of
      miR-582-5p and AKT3 expression was inversely correlated with miR-582-5p
      expression. Besides, AKT3 upregulation efficiently abrogates the effect of miR
      582-5p on the cells. These results demonstrated that miR-582-5p regulates cell
      proliferation and apoptosis in human endometrial carcinoma via AKT3. Thus, miR
      582-5p represents a potential therapeutic target in human endometrial carcinoma
      meriting further investigation.

PMID- 30108447
TI  - Intervention of integrative medicine treatment has impact on serum levels of ET
      1, TNF-alpha, MLT in RA-CVD.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease that can destroy
      peripheral joints. However, very little is known regarding specific biological
      marker for RA in Chinese patients. In this study, we determined the serum
      biomarkers and clinical features of RA-CVD. We also evaluated the short-term
      efficacy of routine RA treatment combined with integrative medicine treatment on
      RA-CVD. We found that anti-cyclic citrullinated peptide (CCP) and disease
      activity score in 28 joints (DAS28) are associated with risks of cardiovascular
      disease (CVD) in RA. And, melatonin (MLT) may play a negative regulatory role in
      cardiovascular damage in patients with RA. Furthermore, endothelin (ET-1) and
      inflammatory markers may be subclinical cardiovascular damages in RA. Moreover,
      of the 17 patients with RA-CVD, test results of ET-1, TNF-alpha and OSCAR after
      integrative medicine treatment were significantly decreased than before
      treatment. Collectively, our results provide a therapeutic potential of
      integrative medicine to the treatment of RA-CVD.

PMID- 30108449
TI  - Bilateral synchronous multiple lung nodules: Surgical experience from two cases.
AB  - Synchronous multiple lung cancer (SMPLC) has been increasingly detected as a
      result of improved imaging techniques, though the incidence of SMPLC is rare.
      Surgery is currently the only treatment offering potential cure and long-term
      survival in patients with SMPLC, and complete resection is widely accepted as the
      first choice of procedure for this type. However, due to the rarity of this
      clinical scenario, many surgeons lack experience in surgical treatment of SMPLC.
      Here, we present two cases whose SMPLC was successfully managed with aggressive
      surgical therapy through video-assisted thoracoscopic surgery.

PMID- 30108450
TI  - Metadherin is an apoptotic modulator in prostate cancer through miR-342-3p
      regulation.
AB  - Prostate cancer is the second most common cancer in men worldwide. This study
      focused to clarify the roles of Metadherin (MTDH) and miR-342-3p in prostate
      cancer. We identified that MTDH was up-regulated and miR-342-3p was down
      regulated in the prostate tissues, and there is an inverse correlation between
      MTDH and miR-342-3p. Functional studies revealed that miR-342-3p directly targets
      MTDH via binding to the 3' untranslated regions (UTRs) in the prostate cancer
      cells. Moreover, we also found MTDH overexpression in DU145 and PC3 cells
      inhibited apoptosis. Subsequently, miR-342-3p has been revealed to reverse the
      MTDH effect on the cellular apoptosis in the further studies. Our results
      indicate that MTDH repress apoptosis of prostate cancer in vitro and provides a
      new strategy for human prostate cancer therapy in the future.

PMID- 30108451
TI  - MicroRNA-4728 serves as a suppressor and antagonist of oncogenic MAPK in Burkitt
      lymphoma.
AB  - Objective: This study identified the biological role of miR-4728 in Burkitt
      lymphoma (BL) process. Methods: Ramos cells were used to analyze MicroRNA-4728
      (miR-4728) biological functions. MiR-4728 expression was investigated in 14
      randomly chosen tumor tissues and 12 noncancerous tissues by qRT-PCR. Cyquant
      assay was used to monitor cell proliferation. Colony formation assay was
      performed to study the effectiveness of miR-4728 on the proliferation of cells.
      The effects of miR-4728 on MAPK signaling pathway were detected by luciferase
      reporter assay. The significance of differences between groups were evaluated by
      SPSS. Results: In this study, MiRNA-4728 was observed to down-regulated in BL
      tissues compared to the noncancerous tissues. Additionally, miR-4728 inhibited
      Ramos cell proliferation. Moreover, miR-4728 overexpression also decreased the
      MAPK signaling activity. Conclusion: Our results suggested that miR-4728 serves
      as a suppressor and antagonist of oncogenic MAPK in Burkitt lymphoma. The
      appropriate regulation of miR-4728 might be vital to improve BL treatment.

PMID- 30108452
TI  - MicroRNA-4728 mediated regulation of MAPK oncogenic signaling in papillary
      thyroid carcinoma.
AB  - Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer that
      accounts for 85% of thyroid cancers. MicroRNAs (miRNAs) have been reported to
      play important roles in the biological processes in cancer. In this study, we
      analyzed the biological role of miR-4728 in human PTC process in human PTC cell
      lines in vitro. MiRNA-4728 was observed to down-regulated in human PTC tissues
      and PTC cell lines. Additionally, miR-4728 inhibited PTC cell proliferation.
      Further study demonstrated SOS1 was repressed by miR-4728 and overexpression of
      miR-4728 down-regulated both the mRNA and protein levels of SOS1. Moreover, miR
      4728 overexpression also decreased the MAPK signaling activity. These
      observations suggested that miR-4728 could inhibit the process of human PTC
      through regulating MAPK signaling pathway. And, appropriate regulation of miR
      4728 might be vital to improve human PTC treatment.

PMID- 30108453
TI  - Anti-tumor and anti-metastatic roles of cordycepin, one bioactive compound of
      Cordyceps militaris.
AB  - Public interest in complementary and alternative medicine has been increased
      worldwide, due to its wide applications in cancer prevention and treatment.
      Cordycepin is one of the most common and crucial types of complementary and
      alternative medicine. Cordycepin (3'-deoxyadenosine), a derivative of adenosine,
      was first isolated from medicine drug Cordyceps militaris. Cordycepin has been
      widely used as one compound for antitumor, which has been found to exert
      antiangiogenic, anti-metastatic, and antiproliferative effects, as well as
      inducing apoptosis. However, the mechanism of its anti-tumor activity is not well
      known. This review will clarify anti-tumor mechanisms of Cordycepin, which
      regulate signaling pathways related with tumor growth and metastasis. Cordycepin
      inhibit tumor growth via upregulating tumor apoptosis, inducing cell cycle arrest
      and targeting cancer stem cells (CSCs). Cordycepin regulates tumor
      microenvironment via suppressing tumor metastasis-related pathways. Thus,
      Cordycepins may be one of important supplement or substitute medicine drug for
      cancer treatment.

PMID- 30108454
TI  - Integrative computational evaluation of genetic markers for Alzheimer's disease.
AB  - Recent studies have reported hundreds of genes linked to Alzheimer's Disease
      (AD). However, many of these candidate genes may be not identified in different
      studies when analyses were replicated. Moreover, results could be controversial.
      Here, we proposed a computational workflow to curate and evaluate AD related
      genes. The method integrates large scale literature knowledge data and gene
      expression data that were acquired from postmortem human brain regions (AD
      case/control: 31/32 and 22/8). Pathway Enrichment, Sub-Network Enrichment, and
      Gene-Gene Interaction analysis were conducted to study the pathogenic profile of
      the candidate genes, with 4 metrics proposed and validated for each gene. By
      using our approach, a scalable AD genetic database was developed, including AD
      related genes, pathways, diseases and info of supporting references. The AD
      case/control classification supported the effectiveness of the 4 proposed
      metrics, which successfully identified 21 well-studied AD genes (i.g. TGFB1,
      CTNNB1, APP, IL1B, PSEN1, PTGS2, IL6, VEGFA, SOD1, AKT1, CDK5, TNF, GSK3B, TP53,
      CCL2, BDNF, NGF, IGF1, SIRT1, AGER and TLR) and highlighted one recently reported
      AD gene (i.g. ITGB1). The computational biology approach and the AD database
      developed in this study provide a valuable resource which may facilitate the
      understanding of the AD genetic profile.

PMID- 30108455
TI  - Survival analysis in Caucasian pulmonary adenocarcinoma patients based on
      differential targets between Caucasian and Asian population.
AB  - Ethnicity differences may contribute to the variety of overall survival in
      pulmonary adenocarcinoma, while the influence of ethnicity relevant somatic
      driver mutations (ERSDM) profile on Caucasian survival is not well investigated.
      In this study, we studied epidermal growth factor receptor (EGFR), tumor protein
      p53 (TP53), Kirsten rat sarcoma 2 viral oncogene homolog (KRAS), and
      Serine/Threonine Kinase 11 (STK11) to construct the ERSDM profile. Those genes
      were selected as harboring somatic driver mutations with >10% prevalence and with
      different occurrence between Caucasian and Asian ethnicity. Clinical information
      and transcriptome sequencing of 173 Caucasian pulmonary adenocarcinoma patients
      with matched mutation data are retrieved from TCGA, Kaplan-Meier analyses and Cox
      proportional-hazards regression models are further used to analyze the effect of
      the ERSDM profile on overall survival. There is no significant correlation
      between single gene mutation and overall survival, while patients with less than
      two mutated genes have a better overall survival compared with those with at
      least two mutated genes (p = 0.034). All of these indicate that multiple
      mutations in the ERSDM profile may be a negative prognostic factor for overall
      survival in Caucasian pulmonary adenocarcinoma patients.

PMID- 30108456
TI  - Large numbers of explanatory variables: a probabilistic assessment.
AB  - Recently, Cox and Battey (2017 Proc. Natl Acad. Sci. USA114, 8592-8595
      (doi:10.1073/pnas.1703764114)) outlined a procedure for regression analysis when
      there are a small number of study individuals and a large number of potential
      explanatory variables, but relatively few of the latter have a real effect. The
      present paper reports more formal statistical properties. The results are
      intended primarily to guide the choice of key tuning parameters.

PMID- 30108457
TI  - Determination of macro-scale soil properties from pore scale structures: image
      based modelling of poroelastic structures.
AB  - We show how a combination of X-ray computed tomography (X-CT) and image-based
      modelling can be used to calculate the effect of moisture content and compaction
      on the macroscopic structural properties of soil. Our method is based on the
      equations derived in Daly & Roose (2018 Proc. R. Soc. A474, 20170141.
      (doi:10.1098/rspa.2017.0141)), which we have extended so they can be directly
      applied to the segmented images obtained from X-CT. We assume that the soils are
      composed of air-filled pore space, solid mineral grains and a mixed phase
      composed of both clay particles and water. We considered three different initial
      soil treatments, composed of two different compaction levels and two different
      moisture contents. We found that the effective properties of the soils were
      unaffected by compaction over the range tested in this paper. However, changing
      the moisture content significantly altered the hydraulic and mechanical
      properties of the soils. A key strength of this method is that it enables the
      optimization or even design of soils composed from different constituents, with
      specific mechanical and hydraulic properties.

PMID- 30108458
TI  - EPID-based daily verification of reproducibility of patients' irradiation with
      IMRT plans.
AB  - Aim: The aim of the work was to catch potential errors with daily EPID
      measurements of repeatability of the dose distribution during irradiation of IMRT
      patients. Materials and methods: In the first stage, measurements were made using
      an anthropomorphic phantom in which the method of collecting data with an EPID
      device and the possibility of detecting errors in positioning were developed.
      Next, for 23 patients, the pelvis (P) and head and neck (H&N) regions, images
      were collected with an EPID device for each IMRT subfield daily and compared to
      reference images using the gamma method (DTA 3 mm, DD 3%). Finally, the
      dependencies between treatment plan parameters, pre-verification results and
      repeatability of collected images were evaluated. Results: The anthropomorphic
      phantom study has shown what kind of effects we can expect with EPID measured at
      potential shifts during radiotherapy. For the clinical case, score results were
      obtained for individual tumor regions as below: (P) 0.786 +/- 1.046, (H&N) 0.720
      +/- 1.552. For most evaluated cases, score values were below 1%: (P) 75.5% and
      (H&N) 83.9% of analyzed fields. 95% of all evaluated data was with the score
      below: (P) 2.86% and (H&N) 3.40%. The relationship between the results of the
      analysis of daily collected images and the results of pre-verification, field
      size and irradiation time was shown. Conclusions: The EPID-based daily
      verification can provide extra information about day-to-day repeatability of
      treatment, without additional dose.

PMID- 30108460
TI  - Mitochondrial DNA Mutations Induced by Carbon Ions Radiation: A Preliminary
      Study.
AB  - Heavy-ion irradiation-induced nuclear DNA damage and mutations have been studied
      comprehensively. However, there is no information about the deleterious effect of
      heavy-ion irradiation on mitochondrial DNA (mtDNA). In this study, 2 typical
      mtDNA mutations were examined, including 4977 deletions and D310 point mutations.
      The 4977 deletions were quantified by real-time polymerase chain reaction, and
      D310 point mutations were analyzed by direct sequencing and a specific enzyme
      digestion genotyping method. Results showed that carbon ions radiation can induce
      temporal fluctuation of mtDNA 4977 deletions in 72 hours after irradiation, while
      survived clones were free from this deletion. Carbon ions induced more D310
      mutations than X-rays, and the single-cell heteroplasmy was eliminated. This is
      the first study investigating mtDNA mutations induced by carbon ions irradiation
      in vitro. These findings would provide fundamental information for further
      investigation of radiation-induced mitochondrial biogenesis.

PMID- 30108459
TI  - Dose-Dependent Antifibrotic Effect of Chrysin on Regression of Liver Fibrosis:
      The Role in Extracellular Matrix Remodeling.
AB  - Liver fibrosis represents an overaccumulation of extracellular matrix (ECM). This
      study was designed to investigate the effect of chrysin on established ECM
      overproduction in carbon tetrachloride (CCl4) mouse liver fibrosis. Experimental
      fibrosis was induced by intraperitoneal injection of 2 mL/kg CCl4 twice a week,
      for 7 weeks. Mice were orally treated with 3 doses of chrysin (5,7
      dihydroxyflavone). For the assessment of the spontaneous reversion of fibrosis,
      CCl4-treated mice were investigated after 2 weeks of recovery time. Silymarin was
      used as a standard of liver protection. In fibrotic livers, the results showed
      the upregulation of collagen I (Col I) and tissue inhibitors of metalloproteinase
      1 (TIMP-1) and modulation of matrix metalloproteinases (MMPs), which led to an
      altered ECM enriched in Col, confirmed as well by electron microscopy
      investigations. Treatment with chrysin significantly reduced ultrastructural
      changes, downregulated Col I, and restored TIMP-1/MMP balance, whereas in the
      group observed for the spontaneous regression of fibrosis, they remained in the
      same pattern with fibrotic livers. In this study, we have shown chrysin efficacy
      to attenuate dose-dependent CCl4-stimulated liver ECM accumulation by regulation
      of MMP/TIMP imbalance and inhibition of Col production. We have shown the dose
      dependent chrysin efficiency in attenuation of CCl4-induced liver ECM
      accumulation by regulation of MMP/TIMP imbalance and inhibition of Col
      production. Our findings suggest that chrysin oral administration may introduce a
      new strategy for treating liver fibrosis in humans.

PMID- 30108461
TI  - Role of febuxostat in retarding progression of diabetic kidney disease with
      asymptomatic hyperuricemia: A 6-months open-label, randomized controlled trial.
AB  - Introduction: Hyperuricemia is associated with chronic kidney disease (CKD)
      progression and poor cardiovascular outcomes. We studied the effect of febuxostat
      on estimated glomerular filtration rate (eGFR), proteinuria and monitored the
      safety profile of the medication. Material and Methods: This is a prospective
      open-label, randomized study in CKD stage 3 and 4 patients with diabetic
      nephropathy and asymptomatic hyperuricemia. Patients were randomized into
      febuxostat 40 mg daily and no treatment group using block randomization method
      and were followed up for 6 months. Their usual care for diabetes mellitus,
      hypertension and dyslipidemia were continued in the study. Blood and urine
      investigations were monitored at baseline, 3 months and 6 months. Results: The
      eGFR in febuxostat group was stabilized at 6 months with no significant reduction
      [26.2 (IQR 14.30) at baseline to 26.3 (IQR 15.2) ml/min/1.73 m2]. Whereas, there
      was a significant reduction of the eGFR in no treatment group from 28.2 (IQR
      17.9) to 27.6 (IQR 19.3) ml/min/1.73 m2 (p value < 0.01). We found the HbA1c
      (glycosylated hemoglobin) was significantly increased in febuxostat group from
      7.2 +/- 0.5 % at baseline to 7.6 +/- 1.4 at 6 months (p value 0.04) but no
      significant change of HbA1c in the no treatment group. Proteinuria level was
      unchanged in both groups. The commonest adverse event was joint pain.
      Conclusions: Febuxostat was able to preserve eGFR in CKD patients with diabetic
      nephropathy and this effect was beyond glycemic control. Increment of HbA1c level
      in febuxostat group needs further larger trials.

PMID- 30108462
TI  - Ectopic microRNAs used to preserve human mesenchymal stem cell potency and
      epigenetics.
AB  - Human mesenchymal stem cells (hMSCs) have remarkable potential for use in
      regenerative medicine. However, one of the great challenges is preserving their
      potency for long time. This study investigated the effect of miRNA ectopic
      expression on their proliferation and also on the expression level of Parp1 as an
      epigenetic switch preserving pluripotency in hMSCs. A cationic liposome was
      prepared as an efficient carrier for miRNA delivery. The miRNA loading efficiency
      and physical stability of vesicles were measured, and their scanning electron
      microscopic shapes determined. hMSCs were transfected with miR-302a and miR-34a
      followed by assessment of their proliferation potency with MTT assay and
      measurement of the expression of Parp1 by quantitative polymerase chain reaction
      (QPCR). Cell transfection with miR-302a and miR-34a efficiently and
      differentially affects the proliferation potency of hMSCs and the expression
      level of Parp1 as the key epigenetic factor involved in pluripotency. While miR
      302a increases Parp1 expression, miR-34a suppresses it significantly, showing
      differential effects. Our results demonstrated that miRNA-based treatments
      represent efficient therapeutic systems and hold a great promise for future use
      in regenerative medicine through modification of hMSC pluripotency and epigenome.

PMID- 30108463
TI  - A-NGR fusion protein induces apoptosis in human cancer cells.
AB  - The NGR peptide is one of the well-known peptides for targeting tumor cells. It
      has the ability to target aminopeptidase N (CD13) on tumor cells or the tumor
      vascular endothelium. In this study, the NGR peptide was used for targeting A
      subunit of the Shiga toxin to cancer cells. The cytotoxic effect of the A-NGR
      fusion protein was assessed on HT1080, U937, HT29 cancer cells and MRC-5 normal
      cells. For this purpose, cells were treated with different concentrations of A
      NGR (0.5-40 ug/ml). The evaluation of cell viability was achieved by MTT assay.
      Apoptosis was determined by annexin-V/PI double staining flow cytometry.
      Alterations in the mRNA expression of apoptosis - related genes were assessed by
      real time RT- PCR. The results showed that A-NGR fusion protein effectively
      inhibited the growth of HT1080 and U937 cancer cells in comparison to negative
      control (PBS) but for CD13-negative HT-29 cancer cells, only at high
      concentrations of fusion protein was inhibited growth recorded. On the other
      hand, A-NGR had little cytotoxic effect on MRC-5 normal cells. The flow cytometry
      results showed that A-NGR induces apoptosis. Furthermore, the results of real
      time RT-PCR revealed that A-NGR significantly increases the mRNA expression of
      caspase 3 and caspase 9. Conclusively, A-NGR fusion protein has the ability of
      targeting CD13-positive cancer cells, the cytotoxic effect on CD13-positive
      cancer cells as well as has low cytotoxic effect on normal cells.

PMID- 30108464
TI  - Targeting PPAR-gamma to design and synthesize antidiabetic thiazolidines.
AB  - A series of thiazolidine derivatives were designed by docking into PPAR-gamma
      active site. The structure of target was obtained from the protein data bank (PDB
      ID P37231). A library of 200 molecules was prepared on random basis. Molecular
      docking studies were performed using VLife MDS 4.3 software. After molecular
      docking studies, the 4-substituted-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimidine
      5-carboxylic acid N-[4-(2,4-dioxo-thiazolidin-5-ylidenemethyl)-phenyl]-hydrazides
      (4a-4h) were selected for synthesis. The progress of reaction and purity of the
      synthesized compounds were monitored by TLC and melting point. Structures of
      title compounds were confirmed by elemental analysis, IR, 1H NMR and mass
      spectral data. The antidiabetic activity of title compounds was performed using
      the Wistar rats by alloxan-induced method. The compounds have shown antidiabetic
      activity comparable with the standard drug pioglitazone. These findings suggest
      that potent antidiabetics can be generated by substituting nonpolar, electron
      withdrawing substituents at the fourth position of pyrimidine skeleton and
      hydrogen bond acceptor at the nitrogen of the thiazolidine nucleus, to inhibit
      peroxisome proliferator-activated receptor-gamma.

PMID- 30108465
TI  - Association between miR-124-1 rs531564 polymorphism and risk of cancer: An
      updated meta-analysis of case-control studies.
AB  - Many studies examined the association between miR-124-1 rs531564 polymorphism and
      the risk of some human cancers, but the findings remain controversial. This
      update meta-analysis aimed to validate the association between rs531564
      polymorphism of miR-124-1 and cancer risk. Eligible studies including 6,502
      cancer cases and 7,213 controls were documented by searching Web of Science,
      PubMed, Scopus, and Google scholar databases. Pooled odds ratios (ORs) with 95 %
      confidence intervals (CIs) were estimated to quantitatively evaluate the
      association between rs531564 variant and cancer risk. The results indicated that
      rs531564 variant significantly decreased the risk of cancer in homozygous
      codominant (OR=0.54, 95 % CI=0.43-0.69, p<0.00001, GG vs CC), dominant (OR=0.84,
      95 % CI=0.72-0.99, p=0.03, CG+GG vs CC), recessive (OR=0.65, 95 % CI=0.54-0.78,
      p<0.00001, GG vs CG+CC), and allele (OR=0.84, 95 % CI=0.73-0.96, p=0.008, G vs C)
      genetic model. Stratified analysis by cancer type revealed that rs531564 variant
      was associated with gastric cancer, cervical cancer, esophageal squamous cell
      carcinoma and colorectal cancer risk. In summary, the findings of this meta
      analysis support an association between miR-124-1 rs531564 polymorphism and
      cancer risk. Larger and well-designed studies are required to estimate this
      association in detail.

PMID- 30108466
TI  - Association of stressful life events and psychological problems profile: Results
      from a large-scale cross-sectional study among Iranian industrial employees using
      Bayesian quantile structural equation model.
AB  - Objectives: The current study aimed at evaluating the major domains of stressful
      life events and their association with psychological problems profile in a large
      sample of Iranian industrial manufacturing employees. Methods: In a cross
      sectional study, 3,063 participants were randomly selected from 16,000 employees
      working in a big industrial company in Isfahan, Iran. Three common psychological
      problems i.e. depression, anxiety and psychological distress were evaluated using
      Persian validated version of Hospital Anxiety and Depression Scale (HADS) and 12
      item General Health Questionnaire (GHQ-12), respectively. Self-perceived
      frequency and intensity of stressful life events were measured by stressful life
      event (SLE) questionnaire. Bayesian quantile structural equation model in R free
      statistical software (version 3.4) was used for evaluating the association of
      stressful life events and levels of psychological problems profile. Results:
      Using factor analysis, two major domains i.e. socioeconomic and personal
      stressors were derived from 11 life stressors and a unified measure i.e.
      psychological problem profile was extracted from three common psychological
      problems. Financial and daily life stressors had the highest and sexual problems
      showed lowest intensity. Quantile structural equation model revealed that the
      psychological problems profile scores had stronger association with personal
      (beta: ranging from 0.45, 1.87) than socioeconomics stressors (beta: ranging from
      0.11, 0.27). The association of socioeconomic stressors was fairly uniform across
      quantiles of psychological problems scores, while personal stressors showed
      stronger association in higher quantiles, meaning that employees with higher
      mental health problems more experienced personal stressors. Conclusions: Life
      stressors particularly personal showed direct association with intensity of
      psychological problems in manufacturing employees. Life stressors are more
      perceived by employees with higher intensity of psychological problems. The
      results of current study can be useful in planning occupational health programs
      in order to improve psychological health and job productivity.

PMID- 30108467
TI  - Long-term administration of melatonin attenuates neuroinflammation in the aged
      mouse brain.
AB  - Aging is often accompanied by a decline in cognitive function in conjunction with
      a variety of neurobiological changes, including neuroinflammation. Melatonin is a
      key endogenous indoleamine secreted by the pineal gland that plays a crucial role
      in the regulation of circadian rhythms, is a potent free radical scavenger, has
      anti-inflammatory activity and serves numerous other functions. However, the role
      of melatonin in sterile inflammation in the brain has not been fully
      investigated. In the present study, we investigated the neuroinflammation status
      in aged mouse brains. The results showed that the protein levels of integrin
      alphaM (CD11b), glial fibrillary acidic protein (GFAP), the major pro
      inflammatory cytokines (interleukin-1 beta [IL-1beta], interleukin-6 [IL-6], and
      tumor necrosis factor alpha [TNF-alpha]) and phosphor-nuclear factor kappa B
      (pNFkappaB) were significantly increased, while N-methyl-D-aspartate (NMDA)
      receptor subunits NR2A and NR2B, Ca2+/calmodulin-dependent protein kinase II
      (CaMKII), and brain-derived neurotrophic factor (BDNF) were down-regulated in the
      hippocampus and prefrontal cortex (PFC) of 22-months-old (aged) mice compared
      with 2-months-old (young adult) mice. Melatonin was administered in the drinking
      water to a cohort of the aged mice at a dose of 10 mg/kg/day, beginning at an age
      of 16 months for 6 months. Our results revealed that melatonin significantly
      attenuated the alterations in these protein levels. The present study suggests an
      advantageous role for melatonin in anti-inflammation, and this may lead to the
      prevention of memory impairment in aging.

PMID- 30108469
TI  - Hair histology as a tool for forensic identification of some domestic animal
      species.
AB  - Animal hair examination at a criminal scene may provide valuable information in
      forensic investigations. However, local reference databases for animal hair
      identification are rare. In the present study, we provide differential
      histological analysis of hair of some domestic animals in Upper Egypt. For this
      purpose, guard hair of large ruminants (buffalo, camel and cow), small ruminants
      (sheep and goat), equine (horse and donkey) and canine (dog and cat) were
      collected and comparative analysis was performed by light microscopy. Based on
      the hair cuticle scale pattern, type and diameter of the medulla, and the
      pigmentation, characteristic differential features of each animal species were
      identified. The cuticle scale pattern was imbricate in all tested animals except
      in donkey, in which coronal scales were identified. The cuticle scale margin
      type, shape and the distance in between were characteristic for each animal
      species. The hair medulla was continuous in most of the tested animal species
      with the exception of sheep, in which fragmental medulla was detected. The
      diameter of the hair medulla and the margins differ according to the animal
      species. Hair shaft pigmentation were not detected in all tested animals with the
      exception of camel and buffalo, in which granules and streak-like pigmentation
      were detected. In conclusion, the present study provides a first-step towards
      preparation of a complete local reference database for animal hair identification
      that can be used in forensic investigations.

PMID- 30108468
TI  - New role of hypoxia in pathophysiology of multiple myeloma through miR-210.
AB  - Bone is one of the most common sites of complication in multiple myeloma (MM)
      progression and bone remodeling gets definitively perturbed during disease
      progression. Hypoxia and miR-210 play an important role in hematological
      malignancies. In an attempt to elucidate the specificity of the pathways of
      hypoxia and miR-210 in suppression of osteoblastic differentiation in MM
      patients, we examined the effect of miR-210 and hypoxia on expression of
      important cytokines and genes of myeloma cells. Differentiation of BM-MSCs
      towards osteoblastic cells in response to microvesicles (MVs) was also
      investigated. Finally, we proposed a molecular model on how HIF-1alpha may
      promote bone lesions in MM patients. To validate the effect of miR-210 and HIF
      1alpha on targeted genes, the shRNA of HIF-1alpha and off-hsa-miR-210 were
      transfected into RPMI-8226 cells. BM-MSCs were cultured in osteoblastic inducer
      and 50 ug/mL of MVs derived from both hypoxic and normoxic myeloma cells. We
      designed an in vitro study to establish the effects of HIF-1alpha and miR-210 on
      the crosstalk between MM and osteoblasts. We here showed that hypoxia-induced miR
      210 increased the mRNA expression of VLA-4, CXCR4, IL-6 and TGF-beta in myeloma
      cells. MiR-210 is mandatory for the hypoxia-increased resistance of MM cells to
      melphalan. Moreover, MVs derived from hypoxic myeloma cells substantially
      decreased osteoblast differentiation. Considered comprehensively, our findings
      explain one of the reasons of bone loss that occurs at the sites of MM and a
      nascent crosstalk model in MM pathogenesis.

PMID- 30108470
TI  - Exploiting in vitro potential and characterization of surface modified Zinc oxide
      nanoparticles of Isodon rugosus extract: Their clinical potential towards HepG2
      cell line and human pathogenic bacteria.
AB  - Little is known about biogenically synthesized Zinc oxide nanoparticles (ZnONPs)
      from Isodon rugosus. Synthesis of metal oxide NPs from essential oil producing
      medicinal plants results in less harmful side effects to the human population as
      compared to chemically synthesized NPs. In this article, we report biogenic
      synthesis of ZnONPs from in vitro derived plantlets and thidiazuron (TDZ) induced
      callus culture of Isodon rugosus. Synthesized NPs were characterized using UV
      spectra, XRD, FTIR, SEM and EDX. Furthermore, the NPs were evaluated for their
      potential cytotoxic (against HepG2 cell line) and antimicrobial (against drug
      resistant Staphylococcus epidermidis, Bacillus subtilis, Klebsiella pneumoniae
      and Pseudomonas aeruginosa) activities. Pure crystalline ZnONPs with hexagonal
      and triangular shapes were obtained as a result of callus extract (CE) and whole
      plant extract (WPE), respectively. ZnONPs showed potent cytotoxic and
      antimicrobial potential. The antimicrobial and cytotoxic activities of ZnONPs
      were found to be shape and surface bound phytochemicals dependent. CE mediated
      hexagonal ZnONPs showed superior anti-cancer and antimicrobial activities as
      compared to WPE mediated triangular shaped ZnONPs. It is concluded that biogenic
      ZnONPs have incredible potential as theranostic agents and can be adopted as
      useful drug delivery system in next generation treatment strategies.

PMID- 30108471
TI  - Pre-pregnancy and early pregnancy dietary behavior in relation to maternal and
      newborn health in the Norwegian Fit for Delivery study - a post hoc observational
      analysis.
AB  - Background: Randomized controlled trials targeting maternal dietary and physical
      activity behaviors during pregnancy have generally failed to accomplish
      reductions in the prevalence of adverse maternal and neonatal outcomes.
      Interventions carried out during pregnancy could thus be missing the mark in
      maximizing intervention health benefit. Objective: To investigate whether pre
      pregnancy and early pregnancy dietary behavior as reported at inclusion into the
      Norwegian Fit for Delivery (NFFD) trial was associated with maternal and neonatal
      outcomes irrespective of subsequent randomization assignment. Design: The study
      is a post-hoc observational analysis of data from a randomized controlled
      lifestyle intervention. We constructed two diet scores from participant responses
      to a 43-item questionnaire that addressed dietary behavior in retrospect (pre
      pregnancy diet score) and dietary behavior at inclusion (early pregnancy diet
      score), respectively. The diet scores ranged from 0 to 10, with higher score
      reflecting healthier dietary behavior. Associations between diet scores and
      maternal and neonatal health outcomes were estimated in multivariate logistic
      regression models. Results: A total of 591 women were eligible for analysis. A
      one-point increase in pre-pregnancy diet score was associated with lower odds of
      excessive gestational weight gain (GWG) (odds ratio [OR]adj: 0.92; 95% confidence
      interval [CI]: 0.84-1.00, p = 0.050), preterm delivery (ORadj: 0.81; 95% CI: 0.68
      0.97, p = 0.019), and birthweight >= 4,000 g (ORadj: 0.88; 95% CI: 0.78-0.99, p =
      0.038). A one-point increase in early pregnancy diet score was associated with
      lower odds of excessive GWG (ORadj: 0.88; 95% CI: 0.79-0.97, p = 0.009), preterm
      delivery (ORadj: 0.82; 95% CI: 0.67-0.99, p = 0.038), and preeclampsia (ORadj:
      0.78; 95% CI: 0.62-0.99, p = 0.038). Discussion: Higher diet score either pre
      pregnancy or in early pregnancy was protectively associated with excessive GWG
      and preterm delivery, whereas the protective association with high birthweight
      was confined to pre-pregnancy diet and with preeclampsia to early pregnancy diet.
      Conclusions: Both pre-pregnancy and early pregnancy dietary behavior was
      associated with important maternal and neonatal health outcomes in the NFFD
      dataset.

PMID- 30108472
TI  - Expanding Brain-Computer Interfaces for Controlling Epilepsy Networks: Novel
      Thalamic Responsive Neurostimulation in Refractory Epilepsy.
AB  - Seizures have traditionally been considered hypersynchronous excitatory events
      and epilepsy has been separated into focal and generalized epilepsy based largely
      on the spatial distribution of brain regions involved at seizure onset. Epilepsy,
      however, is increasingly recognized as a complex network disorder that may be
      distributed and dynamic. Responsive neurostimulation (RNS) is a recent technology
      that utilizes intracranial electroencephalography (EEG) to detect seizures and
      delivers stimulation to cortical and subcortical brain structures for seizure
      control. RNS has particular significance in the clinical treatment of medically
      refractory epilepsy and brain-computer interfaces in epilepsy. Closed loop RNS
      represents an important step forward to understand and target nodes in the
      seizure network. The thalamus is a central network node within several functional
      networks and regulates input to the cortex; clinically, several thalamic nuclei
      are safe and feasible targets. We highlight the network theory of epilepsy,
      potential targets for neuromodulation in epilepsy and the first reported use of
      RNS as a first generation brain-computer interface to detect and stimulate the
      centromedian intralaminar thalamic nucleus in a patient with bilateral cortical
      onset of seizures. We propose that advances in network analysis and
      neuromodulatory techniques using brain-computer interfaces will significantly
      improve outcomes in patients with epilepsy. There are numerous avenues of future
      direction in brain-computer interface devices including multi-modal sensors,
      flexible electrode arrays, multi-site targeting, and wireless communication.

PMID- 30108474
TI  - Visualization of the Membranous Labyrinth and Nerve Fiber Pathways in Human and
      Animal Inner Ears Using MicroCT Imaging.
AB  - Design and implantation of bionic implants for restoring impaired hair cell
      function relies on accurate knowledge about the microanatomy and nerve fiber
      pathways of the human inner ear and its variation. Non-destructive isotropic
      imaging of soft tissues of the inner ear with lab-based microscopic X-ray
      computed tomography (microCT) offers high resolution but requires contrast
      enhancement using compounds with high X-ray attenuation. We evaluated different
      contrast enhancement techniques in mice, cat, and human temporal bones to
      differentially visualize the membranous labyrinth, sensory epithelia, and their
      innervating nerves together with the facial nerve and middle ear. Lugol's iodine
      potassium iodine (I2KI) gave high soft tissue contrast in ossified specimens but
      failed to provide unambiguous identification of smaller nerve fiber bundles
      inside small bony canals. Fixation or post-fixation with osmium tetroxide
      followed by decalcification in EDTA provided superior contrast for nerve fibers
      and membranous structures. We processed 50 human temporal bones and acquired
      microCT scans with 15 MUm voxel size. Subsequently we segmented sensorineural
      structures and the endolymphatic compartment for 3D representations to serve for
      morphometric variation analysis. We tested higher resolution image acquisition
      down to 3.0 MUm voxel size in human and 0.5 MUm in mice, which provided a unique
      level of detail and enabled us to visualize single neurons and hair cells in the
      mouse inner ear, which could offer an alternative quantitative analysis of cell
      numbers in smaller animals. Bigger ossified human temporal bones comprising the
      middle ear and mastoid bone can be contrasted with I2KI and imaged in toto at 25
      MUm voxel size. These data are suitable for surgical planning for electrode
      prototype placements. A preliminary assessment of geometric changes through
      tissue processing resulted in 1.6% volume increase caused during decalcification
      by EDTA and 0.5% volume increase caused by partial dehydration to 70% ethanol,
      which proved to be the best mounting medium for microCT image acquisition.

PMID- 30108473
TI  - Inhibition of Diacylglycerol Lipase Impairs Fear Extinction in Mice.
AB  - Elucidating the underlying molecular mechanisms regulating fear and extinction
      learning may offer insights that can lead to novel treatments for debilitating
      anxiety and trauma-related disorders including posttraumatic stress disorder. The
      endocannabinoid (eCB) system is a retrograde inhibitory signaling pathway
      involved in regulating central responses to stress. The eCB 2
      arachidonoylglycerol (2-AG) has recently been proposed to serve as a homeostatic
      signal mitigating adverse effects of stress exposure, however, less well
      understood is 2-AG's role in fear learning and fear extinction. In this study, we
      have sought to explore 2-AG's role in fear conditioning and fear extinction by
      disrupting 2-AG synthesis utilizing the DAGL inhibitor (DO34) and DAGLalpha knock
      out mice (DAGLalpha-/-). We found that DAGLalpha-/- mice, and male and female
      C57B6/J mice treated with DO34, exhibited impairment in extinction learning in an
      auditory cue fear-conditioning paradigm. DO34 did not increase unconditioned
      freezing. Interestingly, inhibition of fatty-acid amide hydrolase was not able to
      restore normal fear extinction in DO34-treated mice suggesting increased
      Anandamide cannot compensate for deficient 2-AG signaling in the regulation of
      fear extinction. Moreover, augmentation of CB1R signaling with
      tetrahydrocannabinol also failed to restore normal fear extinction in DO34
      treated mice. Overall, these data support the hypothesis that DAGLalpha plays an
      important role in fear extinction learning. Although genetic and pharmacological
      disruption of DAGL activity causes widespread lipidomic remodeling, these data
      combined with previous studies putatively suggest that deficient 2-AG signaling
      could be a susceptibility endophenotype for the development of trauma-related
      psychiatric disorders.

PMID- 30108476
TI  - Performance Differences Using a Vibro-Tactile P300 BCI in LIS-Patients Diagnosed
      With Stroke and ALS.
AB  - Patients with locked-in syndrome (LIS) are typically unable to move or
      communicate and can be misdiagnosed as patients with disorders of consciousness
      (DOC). Behavioral assessment scales are limited in their ability to detect signs
      of consciousness in this population. Recent research has shown that brain
      computer interface (BCI) technology could supplement behavioral scales and allows
      to establish communication with these severely disabled patients. In this study,
      we compared the vibro-tactile P300 based BCI performance in two groups of
      patients with LIS of different etiologies: stroke (n = 6) and amyotrophic lateral
      sclerosis (ALS) (n = 9). Two vibro-tactile paradigms were administered to the
      patients to assess conscious function and command following. The first paradigm
      is called vibrotactile evoked potentials (EPs) with two tactors (VT2), where two
      stimulators were placed on the patient's left and right wrist, respectively. The
      patients were asked to count the rare stimuli presented to one wrist to elicit a
      P300 complex to target stimuli only. In the second paradigm, namely vibrotactile
      EPs with three tactors (VT3), two stimulators were placed on the wrists as done
      in VT2, and one additional stimulator was placed on his/her back. The task was to
      count the rare stimuli presented to one wrist, to elicit the event-related
      potentials (ERPs). The VT3 paradigm could also be used for communication. For
      this purpose, the patient had to count the stimuli presented to the left hand to
      answer "yes" and to count the stimuli presented to the right hand to answer "no."
      All patients except one performed above chance level in at least one run in the
      VT2 paradigm. In the VT3 paradigm, all 6 stroke patients and 8/9 ALS patients
      showed at least one run above chance. Overall, patients achieved higher
      accuracies in VT2 than VT3. LIS patients due to ALS exhibited higher accuracies
      that LIS patients due to stroke, in both the VT2 and VT3 paradigms. These initial
      data suggest that controlling this type of BCI requires specific cognitive
      abilities that may be impaired in certain sub-groups of severely motor-impaired
      patients. Future studies on a larger cohort of patients are needed to better
      identify and understand the underlying cortical mechanisms of these differences.

PMID- 30108475
TI  - Oxytocin Enhancement of Emotional Empathy: Generalization Across Cultures and
      Effects on Amygdala Activity.
AB  - Accumulating evidence suggests that the neuropeptide oxytocin (OXT) can enhance
      empathy although it is unclear which specific behavioral and neural aspects are
      influenced, and whether the effects are modulated by culture, sex, and trait
      autism. Based on previous findings in Caucasian men, we hypothesized that a
      single intranasal dose of OXT would specifically enhance emotional empathy (EE)
      via modulatory effects on the amygdala in an Asian (Chinese) population and
      explored the modulatory role of sex and trait autism on the effects. We first
      conducted a double-blind, randomized between-subject design experiment using a
      modified version of the multifaceted empathy task to determine whether OXT's
      facilitation of EE can be replicated in Chinese men (n = 60). To further explore
      neural mechanisms behind and potential sex differences, functional MRI and skin
      conductance measures were acquired in an independent experiment incorporating men
      and women (n = 72). OXT enhanced EE across experiments and sex, an effect that
      was accompanied by reduced amygdala activity and increased skin conductance
      responses. On the network level OXT enhanced functional coupling of the right
      amygdala with the insula and posterior cingulate cortex for positive valence
      stimuli but attenuated coupling for negative valence stimuli. The effect of OXT
      on amygdala functional connectivity with the insula was modulated by trait
      autism. Overall, our findings provide further support for the role of OXT in
      facilitating EE and demonstrate that effects are independent of culture and sex
      and involve modulatory effects on the amygdala and its interactions with other
      key empathy regions.

PMID- 30108477
TI  - Diet Can Impact Microbiota Composition in Children With Autism Spectrum Disorder.
AB  - Diet is one of the most influential environmental factors in determining the
      composition of the gastrointestinal microbiota. Microbial dysbiosis in children
      with Autism Spectrum Disorder (ASD) and the impact of some bacterial taxa on
      symptoms of ASD has been recognized. Children with ASD are often described as
      picky eaters with low intake of fiber-rich foods, including fruits and
      vegetables. However, the impact of diet on the microbiota composition in children
      with ASD is largely unknown. Herein, fecal samples, 3 day food diaries and the
      Youth and Adolescence Food Frequency questionnaire (YAQ) were collected from
      children with ASD (ASD; n = 26) and unaffected controls (CONT; n = 32).
      Children's ASD symptoms were determined using the Pervasive Developmental
      Disorder Behavior Inventory Screening Version (PDDBI-SV). Differences in the
      microbiota composition at the phyla, order, family, and genus level between ASD
      and CONT were observed. Microbiota composition of children with ASD was
      investigated in relation to feeding behavior, nutrient and food group intake as
      well as dietary patterns derived from the YAQ. In children with ASD, two distinct
      dietary patterns (DP) were associated with unique microbial profiles. DP1,
      characterized by higher intakes of vegetables, legumes, nuts and seeds, fruit,
      refined carbohydrates, and starchy vegetables, but lower intakes of sweets, was
      associated with lower abundance of Enterobacteriaceae, Lactococcus, Roseburia,
      Leuconostoc, and Ruminococcus. DP2, characterized by low intakes of vegetables,
      legumes, nuts and seeds and starchy vegetables, was associated with higher
      Barnesiellaceae and Alistipes and lower Streptophyta, as well as higher levels of
      propionate, isobutyrate, valerate, and isovalerate. Peptostreptococcaceae and
      Faecalibacterium predicted social deficit scores in children with ASD as measured
      by the PDDBI-SV. Diet-associated microbial profiles were related to GI symptoms,
      but no significant interaction between nutrition and microbiota in predicting
      social deficit scores were observed. In conclusion, dietary patterns associated
      with fecal microbiota composition and VFA concentrations in children with ASD
      were identified. Future studies using a larger sample size and measuring other
      behaviors associated with ASD are needed to investigate whether dietary intake
      may be a modifiable moderator of ASD symptoms.

PMID- 30108478
TI  - Distinction Between Variability-Based Modulation and Mean-Based Activation
      Revealed by BOLD-fMRI and Eyes-Open/Eyes-Closed Contrast.
AB  - Recent BOLD-fMRI studies have revealed spatial distinction between variability-
      and mean-based between-condition differences, suggesting that BOLD variability
      could offer complementary and even orthogonal views of brain function with
      traditional activation. However, these findings were mainly observed in block
      designed fMRI studies. As block design may not be appreciate for characterizing
      the low-frequency dynamics of BOLD signal, the evidences suggesting the
      distinction between BOLD variability and mean are less convincing. Based on the
      high reproducibility of signal variability modulation between continuous eyes
      open (EO) and eyes-closed (EC) states, here we employed EO/EC paradigm and BOLD
      fMRI to compare variability- and mean-based EO/EC differences while the subjects
      were in light. The comparisons were made both on block-designed and continuous
      EO/EC data. Our results demonstrated that the spatial patterns of variability-
      and mean-based EO/EC differences were largely distinct with each other, both for
      block-designed and continuous data. For continuous data, increases of BOLD
      variability were found in secondary visual cortex and decreases were mainly in
      primary auditory cortex, primary sensorimotor cortex and medial nuclei of
      thalamus, whereas no significant mean-based differences were observed. For the
      block-designed data, the pattern of increased variability resembled that of
      continuous data and the negative regions were restricted to medial thalamus and a
      few clusters in auditory and sensorimotor networks, whereas activation regions
      were mainly located in primary visual cortex and lateral nuclei of thalamus.
      Furthermore, with the expanding window analyses we found variability results of
      continuous data exhibited a rather slower dynamical process than typically
      considered for task activation, suggesting block design is less optimal than
      continuous design in characterizing BOLD variability. In sum, we provided more
      solid evidences that variability-based modulation could represent orthogonal
      views of brain function with traditional mean-based activation.

PMID- 30108479
TI  - Repeated Bout Rate Enhancement Is Elicited by Various Forms of Finger Tapping.
AB  - Voluntary rhythmic movements, such as, for example, locomotion and other cyclic
      tasks, are fundamental during everyday life. Patients with impaired neural or
      motor function often take part in rehabilitation programs, which include rhythmic
      movements. Therefore, it is imperative to have the best possible understanding of
      control and behaviour of human voluntary rhythmic movements. A behavioural
      phenomenon termed repeated bout rate enhancement has been established as an
      increase of the freely chosen index finger tapping frequency during the second of
      two consecutive tapping bouts. The present study investigated whether the
      phenomenon would be elicited when the first bout consisted of imposed passive
      finger tapping or air tapping. These two forms of tapping were applied since they
      can be performed without descending drive (passive tapping) and without afferent
      feedback related to impact (air tapping) - as compared to tapping on a surface.
      Healthy individuals (n = 33) performed 3-min tapping bouts separated by 10 min
      rest. Surface electromyographic, kinetic, and kinematic data were recorded.
      Supportive experiments were made to measure, for example, the cortical sensory
      evoked potential (SEP) response during the three different forms of tapping.
      Results showed that tapping frequencies in the second of two consecutive bouts
      increased by 12.9 +/- 14.8% (p < 0.001), 9.9 +/- 6.0% (p = 0.001), and 16.8 +/-
      13.6% (p = 0.005) when the first bout had consisted of tapping, passive tapping,
      and air tapping, respectively. Rate enhancement occurred without increase in
      muscle activation. Besides, the rate enhancements occurred despite that tapping,
      as compared with passive tapping and air tapping, resulted in different cortical
      SEP responses. Based on the present findings, it can be suggested that sensory
      feedback in an initial bout increases the excitability of the spinal central
      pattern generators involved in finger tapping. This can eventually explain the
      phenomenon of repeated bout rate enhancement seen after a consecutive bout of
      finger tapping.

PMID- 30108481
TI  - New Insights Into Permeation of Large Cations Through ATP-Gated P2X Receptors.
AB  - The permeability of large cations through the P2X pore has remained arguably the
      most controversial and complicated topic in P2X-related research, with the
      emergence of conflicting studies on the existence, mechanism and physiological
      relevance of a so-called "dilated" state. Due to the important role of several
      "dilating" P2X subtypes in numerous diseases, a clear and detailed understanding
      of this phenomenon represents a research priority. Recent advances, however, have
      challenged the existence of a progressive, ATP-induced pore dilation, by
      demonstrating that this phenomenon is an artifact of the method employed. Here,
      we discuss briefly the history of this controversial and enigmatic dilated state,
      from its initial discovery to its recent reconsideration. We will discuss the
      literature in which mechanistic pathways to a large cation-permeable state are
      proposed, as well as important advances in the methodology employed to study this
      elusive state. Considering recent literature, we will also open the discussion as
      to whether an intrinsically dilating P2X pore exists, as well as the
      physiological relevance of such a large cation-permeable pore and its potential
      use as therapeutic pathway.

PMID- 30108482
TI  - Sex Differences in Synaptic Plasticity: Hormones and Beyond.
AB  - Notable sex-differences exist between neural structures that regulate sexually
      dimorphic behaviors such as reproduction and parenting. While anatomical
      differences have been well-characterized, advancements in neuroimaging and
      pharmacology techniques have allowed researchers to identify differences between
      males and females down to the level of the synapse. Disparate mechanisms at the
      synaptic level contribute to sex-specific neuroplasticity that is reflected in
      sex-dependent behaviors. Many of these synaptic differences are driven by the
      endocrine system and its impact on molecular signaling and physiology. While sex
      dependent modifications exist at baseline, further differences emerge in response
      to stimuli such as stressors. While some of these mechanisms are unifying between
      sexes, they often have directly opposing consequences in males and females. This
      variability is tied to gonadal steroids and their interactions with intra- and
      extra-cellular signaling mechanisms. This review article focuses on the various
      mechanisms by which sex can alter synaptic plasticity, both directly and
      indirectly, through steroid hormones such as estrogen and testosterone. That sex
      can drive neuroplasticity throughout the brain, highlights the importance of
      understanding sex-dependent neural mechanisms of the changing brain to enhance
      interpretation of results regarding males and females. As mood and stress
      responsivity are characterized by significant sex-differences, understanding the
      molecular mechanisms that may be altering structure and function can improve our
      understanding of these behavioral and mental characteristics.

PMID- 30108480
TI  - An Oral Combination of Vitamins A, C, E, and Mg++ Improves Auditory Thresholds in
      Age-Related Hearing Loss.
AB  - The increasing rate of age-related hearing loss (ARHL), with its subsequent
      reduction in quality of life and increase in health care costs, requires new
      therapeutic strategies to reduce and delay its impact. The goal of this study was
      to determine if ARHL could be reduced in a rat model by administering a
      combination of antioxidant vitamins A, C, and E acting as free radical scavengers
      along with Mg++, a known powerful cochlear vasodilator (ACEMg). Toward this goal,
      young adult, 3 month-old Wistar rats were divided into two groups: one was fed
      with a diet composed of regular chow ("normal diet," ND); the other received a
      diet based on chow enriched in ACEMg ("enhanced diet," ED). The ED feeding began
      10 days before the noise stimulation. Auditory brainstem recordings (ABR) were
      performed at 0.5, 1, 2, 4, 8, 16, and 32 kHz at 3, 6-8, and 12-14 months of age.
      No differences were observed at 3 months of age, in both ND and ED animals. At 6
      8 and 12-14 months of age there were significant increases in auditory thresholds
      and a reduction in the wave amplitudes at all frequencies tested, compatible with
      progressive development of ARHL. However, at 6-8 months threshold shifts in ED
      rats were significantly lower in low and medium frequencies, and wave amplitudes
      were significantly larger at all frequencies when compared to ND rats. In the
      oldest animals, differences in the threshold shift persisted, as well as in the
      amplitude of the wave II, suggesting a protective effect of ACEMg on auditory
      function during aging. These findings indicate that oral ACEMg may provide an
      effective adjuvant therapeutic intervention for the treatment of ARHL, delaying
      the progression of hearing impairment associated with age.

PMID- 30108483
TI  - Human Mesenchymal Stem Cells Expressing Erythropoietin Enhance Survivability of
      Retinal Neurons Against Oxidative Stress: An In Vitro Study.
AB  - Retinal degeneration is a prominent feature in ocular disorders. In exploring
      possible treatments, Mesenchymal Stem Cells (MSCs) have been recognized to yield
      therapeutic role for retinal degenerative diseases. Studies have also displayed
      that erythropoietin (EPO) administration into degenerative retina models confers
      significant neuroprotective actions in limiting pathological cell death. In this
      study, we aimed to use MSCs to deliver EPO and to evaluate the ability of EPO to
      rescue retinal neurons from dying upon reactive oxidative stress induction. We
      derived human MSCs from Wharton's jelly (hWJMSCs) of the umbilical cord and cells
      were transduced with lentivirus particles encoding EPO and a reporter gene of
      green fluorescent protein (GFP). The supernatants of both transduced and non
      transduced cells were collected and used as a pre-conditioning medium for Y79
      retinoblastoma cells (retinal neuron cell line) following exposure to glutamate
      induction. Retinal cells exposed to glutamate showed reduced mitochondrial
      depolarization and enhanced improvement in cell viability when incubated with pre
      conditioned media of transduced cells. Our results established a proof-of-concept
      that MSCs could be used as a candidate for the delivery of EPO therapeutic gene
      in the treatment of retinal degenerations.

PMID- 30108484
TI  - PolyQ Tract Toxicity in SCA1 is Length Dependent in the Absence of CAG Repeat
      Interruption.
AB  - Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative
      disorder caused by an expansion of a polyglutamine tract within the ATXN1 gene.
      Normal alleles have been reported to range from 6 to 35 repeats, intermediate
      alleles from 36 to 38 repeats and fully penetrant pathogenic alleles have at
      least 39 repeats. This distribution was based on relatively few samples and the
      narrow intermediate range makes the accuracy of the repeat sizing crucial for
      interpreting and reporting diagnostic tests, which can vary between laboratories.
      Here, we examine the distribution of 6378 SCA1 chromosomes and identify a very
      late onset SCA1 family with a fully penetrant uninterrupted pathogenic allele
      containing 38 repeats. This finding supports the theory that polyQ toxicity is
      related to the increase of the length of the inherited tracts and not as
      previously hypothesized to the structural transition occurring above a specific
      threshold. In addition, the threshold of toxicity shifts to a shorter polyQ
      length with the increase of the lifespan in SCA1. Furthermore, we show that SCA1
      intermediate alleles have a different behavior compared to the other
      polyglutamine disorders as they do not show reduced penetrance when
      uninterrupted. Therefore, the pathogenic mechanism in SCA1 is distinct from other
      cytosine-adenine-guanine (CAG) repeat disorders. Accurately sizing repeats is
      paramount in precision medicine and can be challenging particularly with
      borderline alleles. We examined plasmids containing cloned CAG repeat tracts
      alongside a triplet repeat primed polymerase chain reaction (TP PCR) CAG repeat
      ladder to improve accuracy in repeat sizing by fragment analysis. This method
      accurately sizes the repeats irrespective of repeat composition or length. We
      also improved the model for calculating repeat length from fragment analysis
      sizing by fragment analyzing 100 cloned repeats of known size. Therefore, we
      recommend these methods for accurately sizing repeat lengths and restriction
      enzyme digestion to identify interruptions for interpretation of a given allele's
      pathogenicity.

PMID- 30108486
TI  - Sex Differences in the Physiological Response to Ethanol of Rat Basolateral
      Amygdala Neurons Following Single-Prolonged Stress.
AB  - Females are more likely to develop post-traumatic stress disorder (PTSD) than
      males. Also, symptoms of PTSD frequently precede alcohol abuse in females.
      Stressful, threat-related stimuli are evaluated by the amygdala, which is
      critical for establishing the emotional salience of environmental stimuli.
      Ethanol and stress have been shown to modify amygdala excitability, but effects
      of acute ethanol on neurons of the basolateral amygdala (BLA) in both males and
      females exposed to stress is unknown. The purpose of this study is to determine
      stress-induced changes in membrane properties of BLA neurons and to determine how
      ethanol modulates these changes in male and female rats. Whole-cell recordings
      were obtained from BLA neurons of both male and female rats exposed to single
      prolonged stress (SPS). Neuronal excitability, quantified as the number of action
      potentials, was determined in current clamp mode by applying a series of
      depolarizing current steps. Hyperpolarization-activated current (Ih) was elicited
      in voltage clamp. Excitability and Ih amplitude were determined before and during
      the superfusion of ethanol (EtOH; 30 mM) in BLA neurons from SPS-treated male and
      female rats. SPS alone did not alter the firing properties of BLA neurons from
      either males or females. However, following SPS, BLA neurons from males and
      females respond differently to ethanol. Superfusion of EtOH (30 mM) inhibited
      spike firing in BLA neurons from rats exposed to SPS, and EtOH-induced inhibition
      was greater in females than in males exposed to stress. Also, EtOH (30 mM)
      selectively decreased Ih amplitude in BLA neurons from SPS-treated male rats from
      171 +/- 46 pA in (pre-EtOH) control to 53 +/- 51 pA in the presence of EtOH (30
      mM). EtOH did not reduce Ih in BLA neurons from SPS-treated females. Together,
      these suggest important sex differences in the physiological responses to EtOH in
      stress disorders such as PTSD, that have high comorbidity with alcohol use
      disorders.

PMID- 30108485
TI  - Intracellular Dynamics in Cuneate Nucleus Neurons Support Self-Stabilizing
      Learning of Generalizable Tactile Representations.
AB  - How the brain represents the external world is an unresolved issue for
      neuroscience, which could provide fundamental insights into brain circuitry
      operation and solutions for artificial intelligence and robotics. The neurons of
      the cuneate nucleus form the first interface for the sense of touch in the brain.
      They were previously shown to have a highly skewed synaptic weight distribution
      for tactile primary afferent inputs, suggesting that their connectivity is
      strongly shaped by learning. Here we first characterized the intracellular
      dynamics and inhibitory synaptic inputs of cuneate neurons in vivo and modeled
      their integration of tactile sensory inputs. We then replaced the tactile inputs
      with input from a sensorized bionic fingertip and modeled the learning-induced
      representations that emerged from varied sensory experiences. The model
      reproduced both the intrinsic membrane dynamics and the synaptic weight
      distributions observed in cuneate neurons in vivo. In terms of higher level model
      properties, individual cuneate neurons learnt to identify specific sets of
      correlated sensors, which at the population level resulted in a decomposition of
      the sensor space into its recurring high-dimensional components. Such vector
      components could be applied to identify both past and novel sensory experiences
      and likely correspond to the fundamental haptic input features these neurons
      encode in vivo. In addition, we show that the cuneate learning architecture is
      robust to a wide range of intrinsic parameter settings due to the neuronal
      intrinsic dynamics. Therefore, the architecture is a potentially generic solution
      for forming versatile representations of the external world in different sensor
      systems.

PMID- 30108489
TI  - SBEMimage: Versatile Acquisition Control Software for Serial Block-Face Electron
      Microscopy.
AB  - We present SBEMimage, an open-source Python-based application to operate serial
      block-face electron microscopy (SBEM) systems. SBEMimage is designed for complex,
      challenging acquisition tasks, such as large-scale volume imaging of neuronal
      tissue or other biological ultrastructure. Advanced monitoring, process control,
      and error handling capabilities improve reliability, speed, and quality of
      acquisitions. Debris detection, autofocus, real-time image inspection, and
      various other quality control features minimize the risk of data loss during long
      term acquisitions. Adaptive tile selection allows for efficient imaging of large
      tissue volumes of arbitrary shape. The software's graphical user interface is
      optimized for remote operation. In its user-friendly viewport, tile grids
      covering the region of interest to be acquired are overlaid on previously
      acquired overview images of the sample surface. Images from other sources, e.g.,
      light microscopes, can be imported and superimposed. SBEMimage complements
      existing DigitalMicrograph (Gatan Microscopy Suite) installations on 3View
      systems but permits higher acquisition rates by interacting directly with the
      microscope's control software. Its modular architecture and the use of
      Python/PyQt make SBEMimage highly customizable and extensible, which allows for
      fast prototyping and will permit adaptation to a wide range of SBEM systems and
      applications.

PMID- 30108490
TI  - Early Life Stress in Rodents: Animal Models of Illness or Resilience?

PMID- 30108488
TI  - Eligibility Traces and Plasticity on Behavioral Time Scales: Experimental Support
      of NeoHebbian Three-Factor Learning Rules.
AB  - Most elementary behaviors such as moving the arm to grasp an object or walking
      into the next room to explore a museum evolve on the time scale of seconds; in
      contrast, neuronal action potentials occur on the time scale of a few
      milliseconds. Learning rules of the brain must therefore bridge the gap between
      these two different time scales. Modern theories of synaptic plasticity have
      postulated that the co-activation of pre- and postsynaptic neurons sets a flag at
      the synapse, called an eligibility trace, that leads to a weight change only if
      an additional factor is present while the flag is set. This third factor,
      signaling reward, punishment, surprise, or novelty, could be implemented by the
      phasic activity of neuromodulators or specific neuronal inputs signaling special
      events. While the theoretical framework has been developed over the last decades,
      experimental evidence in support of eligibility traces on the time scale of
      seconds has been collected only during the last few years. Here we review, in the
      context of three-factor rules of synaptic plasticity, four key experiments that
      support the role of synaptic eligibility traces in combination with a third
      factor as a biological implementation of neoHebbian three-factor learning rules.

PMID- 30108491
TI  - tDCS Modulatory Effect on Reading Processes: A Review of Studies on Typical
      Readers and Individuals With Dyslexia.
AB  - The possibility to use non-invasive brain stimulation to modulate reading
      performance in individuals with developmental dyslexia (DD) has been recently
      explored by few empirical investigations. The present systematic review includes
      nine studies which have employed transcranial direct current stimulation (tDCS)
      aiming at improving reading abilities in both typical readers and individuals
      with DD. Anodal tDCS over the left temporo-parietal cortex-a region which is
      typically involved in phonological and orthographic processing during reading
      tasks and underactive in individuals with DD-was the most frequently used
      montage. The majority of studies employing such stimulation protocol showed
      significant improvement in differential reading subprocesses. More precisely,
      word decoding was improved in adult readers, whereas non-word and low-frequency
      word reading in younger individuals. Furthermore, tDCS was found to be
      specifically effective in poor readers and individuals with DD rather than
      typical readers, in spite of the specific brain region targeted by the
      stimulation; Left frontal, left temporo-parietal, and right cerebellar tDCS
      failed to modulate reading in already proficient readers. Overall, tDCS appears
      to be a promising remedial tool for reading difficulties, even when applied to
      younger populations with reading problems. Further empirical evidence is needed
      to confirm the potential of neuromodulation as a successful intervention method
      for DD.

PMID- 30108487
TI  - Revisiting Netrin-1: One Who Guides (Axons).
AB  - Proper patterning of the nervous system requires that developing axons find
      appropriate postsynaptic partners; this entails microns to meters of extension
      through an extracellular milieu exhibiting a wide range of mechanical and
      chemical properties. Thus, the elaborate networks of fiber tracts and non
      fasciculated axons evident in mature organisms are formed via complex
      pathfinding. The macroscopic structures of axon projections are highly
      stereotyped across members of the same species, indicating precise mechanisms
      guide their formation. The developing axon exhibits directionally biased growth
      toward or away from external guidance cues. One of the most studied guidance cues
      is netrin-1, however, its presentation in vivo remains debated. Guidance cues can
      be secreted to form soluble or chemotactic gradients or presented bound to cells
      or the extracellular matrix to form haptotactic gradients. The growth cone, a
      highly specialized dynamic structure at the end of the extending axon, detects
      these guidance cues via transmembrane receptors, such as the netrin-1 receptors
      deleted in colorectal cancer (DCC) and UNC5. These receptors orchestrate
      remodeling of the cytoskeleton and cell membrane through both chemical and
      mechanotransductive pathways, which result in traction forces generated by the
      cytoskeleton against the extracellular environment and translocation of the
      growth cone. Through intracellular signaling responses, netrin-1 can trigger
      either attraction or repulsion of the axon. Here we review the mechanisms by
      which the classical guidance cue netrin-1 regulates intracellular effectors to
      respond to the extracellular environment in the context of axon guidance during
      development of the central nervous system and discuss recent findings that
      demonstrate the critical importance of mechanical forces in this process.

PMID- 30108494
TI  - Factorized Computation: What the Neocortex Can Tell Us About the Future of
      Computing.

PMID- 30108493
TI  - Empathic Neural Responses Predict Group Allegiance.
AB  - Watching another person in pain activates brain areas involved in the sensation
      of our own pain. Importantly, this neural mirroring is not constant; rather, it
      is modulated by our beliefs about their intentions, circumstances, and group
      allegiances. We investigated if the neural empathic response is modulated by
      minimally-differentiating information (e.g., a simple text label indicating
      another's religious belief), and if neural activity changes predict ingroups and
      outgroups across independent paradigms. We found that the empathic response was
      larger when participants viewed a painful event occurring to a hand labeled with
      their own religion (ingroup) than to a hand labeled with a different religion
      (outgroup). Counterintuitively, the magnitude of this bias correlated positively
      with the magnitude of participants' self-reported empathy. A multivariate
      classifier, using mean activity in empathy-related brain regions as features,
      discriminated ingroup from outgroup with 72% accuracy; the classifier's
      confidence correlated with belief certainty. This classifier generalized
      successfully to validation experiments in which the ingroup condition was based
      on an arbitrary group assignment. Empathy networks thus allow for the
      classification of long-held, newly-modified and arbitrarily-formed ingroups and
      outgroups. This is the first report of a single machine learning model on neural
      activation that generalizes to multiple representations of ingroup and outgroup.
      The current findings may prove useful as an objective diagnostic tool to measure
      the magnitude of one's group affiliations, and the effectiveness of interventions
      to reduce ingroup biases.

PMID- 30108492
TI  - Subjective Vividness of Kinesthetic Motor Imagery Is Associated With the
      Similarity in Magnitude of Sensorimotor Event-Related Desynchronization Between
      Motor Execution and Motor Imagery.
AB  - In the field of psychology, it has been well established that there are two types
      of motor imagery such as kinesthetic motor imagery (KMI) and visual motor imagery
      (VMI), and the subjective evaluation for vividness of motor imagery each differs
      across individuals. This study aimed to examine how the motor imagery ability
      assessed by the psychological scores is associated with the physiological measure
      using electroencephalogram (EEG) sensorimotor rhythm during KMI task. First, 20
      healthy young individuals evaluated subjectively how vividly they can perform
      each of KMI and VMI by using the Kinesthetic and Visual Imagery Questionnaire
      (KVIQ). We assessed their motor imagery abilities by summing each of KMI and VMI
      scores in KVIQ (KMItotal and VMItotal). Second, in physiological experiments,
      they repeated two strengths (10 and 40% of maximal effort) of isometric voluntary
      wrist-dorsiflexion. Right after each contraction, they also performed its KMI.
      The scalp EEGs over the sensorimotor cortex were recorded during the tasks. The
      EEG power is known to decrease in the alpha-and-beta band (7-35 Hz) from resting
      state to performing state of voluntary contraction (VC) or motor imagery. This
      phenomenon is referred to as event-related desynchronization (ERD). For each
      strength of the tasks, we calculated the maximal peak of ERD during VC, and that
      during its KMI, and measured the degree of similarity (ERDsim) between them. The
      results showed significant negative correlations between KMItotal and ERDsim for
      both strengths (p < 0.05) (i.e., the higher the KMItotal, the smaller the
      ERDsim). These findings suggest that in healthy individuals with higher motor
      imagery ability from a first-person perspective, KMI efficiently engages the
      shared cortical circuits corresponding with motor execution, including the
      sensorimotor cortex, with high compliance.

PMID- 30108496
TI  - Spatiotemporal Analysis of Developing Brain Networks.
AB  - Recent advances in MRI have made it easier to collect data for studying human
      structural and functional connectivity networks. Computational methods can reveal
      complex spatiotemporal dynamics of the human developing brain. In this paper, we
      propose a Developmental Meta-network Decomposition (DMD) method to decompose a
      series of developmental networks into a set of Developmental Meta-networks (DMs),
      which reveal the underlying changes in connectivity over development. DMD
      circumvents the limitations of traditional static network decomposition methods
      by providing a novel exploratory approach to capture the spatiotemporal dynamics
      of developmental networks. We apply this method to structural correlation
      networks of cortical thickness across subjects at 3-20 years of age, and identify
      four DMs that smoothly evolve over three stages, i.e., 3-6, 7-12, and 13-20 years
      of age. We analyze and highlight the characteristic connections of each DM in
      relation to brain development.

PMID- 30108495
TI  - Parameter Optimization Using Covariance Matrix Adaptation-Evolutionary Strategy
      (CMA-ES), an Approach to Investigate Differences in Channel Properties Between
      Neuron Subtypes.
AB  - Computational models in neuroscience can be used to predict causal relationships
      between biological mechanisms in neurons and networks, such as the effect of
      blocking an ion channel or synaptic connection on neuron activity. Since
      developing a biophysically realistic, single neuron model is exceedingly
      difficult, software has been developed for automatically adjusting parameters of
      computational neuronal models. The ideal optimization software should work with
      commonly used neural simulation software; thus, we present software which works
      with models specified in declarative format for the MOOSE simulator. Experimental
      data can be specified using one of two different file formats. The fitness
      function is customizable as a weighted combination of feature differences. The
      optimization itself uses the covariance matrix adaptation-evolutionary strategy,
      because it is robust in the face of local fluctuations of the fitness function,
      and deals well with a high-dimensional and discontinuous fitness landscape. We
      demonstrate the versatility of the software by creating several model examples of
      each of four types of neurons (two subtypes of spiny projection neurons and two
      subtypes of globus pallidus neurons) by tuning to current clamp data.
      Optimizations reached convergence within 1,600-4,000 model evaluations (200-500
      generations * population size of 8). Analysis of the parameters of the best
      fitting models revealed differences between neuron subtypes, which are consistent
      with prior experimental results. Overall our results suggest that this easy-to
      use, automatic approach for finding neuron channel parameters may be applied to
      current clamp recordings from neurons exhibiting different biochemical markers to
      help characterize ionic differences between other neuron subtypes.

PMID- 30108497
TI  - Differentially Altered NMDAR Dependent and Independent Long-Term Potentiation in
      the CA3 Subfield in a Model of Anti-NMDAR Encephalitis.
AB  - Purpose: Autoantibodies against NMDA receptors (NMDAR) in the cerebrospinal fluid
      (CSF) from anti-NMDAR encephalitis patients have been suggested to be pathogenic
      since in previous studies using patient CSF, NMDAR-dependent processes such as
      long-term potentiation (LTP) were compromised. However, autoantibodies may
      represent a family of antibodies targeted against different epitopes, and CSF may
      contain further autoantibodies. Here, we tested the specificity of the
      autoantibody by comparing NMDAR-dependent and NMDAR-independent LTP within the
      same hippocampal subfield, CA3, using CSF samples from four anti-NMDAR
      encephalitis patients and three control patients. Methods: We performed a
      stereotactic injection of patient-derived cell-free CSF with proven presence or
      absence of NMDAR-antibodies into the rat hippocampus in vivo. Hippocampal brain
      slices were prepared 1-8 days after intrahippocampal injection, and NMDAR
      dependent LTP at the associational-commissural (A/C) fiber-CA3 synapse was
      compared to NMDAR-independent LTP at the mossy fiber (MF)-CA3 synapse. Results:
      The LTP magnitude at A/C fiber-CA3 synapses in slices from control-CSF-treated
      animals (168 +/- 8% n = 54) was significantly higher than LTP in slices from
      NMDAR-CSF-treated animals (139 +/- 9%, n = 40; P = 0.015), although there was
      some variation between the individual CSF samples. We found residual LTP in NMDAR
      CSF-treated tissue which could be abolished by the NMDAR inhibitor D-AP5.
      Moreover, the CA3 field excitatory postsynaptic potential (fEPSP) was followed by
      epileptiform afterpotentials in 5% of slices (4/78) from control-CSF-treated
      animals, but in 26% of slices (12/46) from NMDAR-CSF-treated animals (P = 0.002).
      Application of the LTP-inducing paradigm increased the proportion of slices with
      epileptiform afterpotentials, but D-AP5 significantly reduced the occurrence of
      epileptiform afterpotentials only in NMDAR-CSF-treated, but not in control
      tissue. At the MF synapse, no significant difference in LTP values of control-CSF
      and in NMDAR-CSF-treated tissue was observed indicating that NMDAR-independent MF
      LTP is intact in NMDAR-CSF-treated tissue. Conclusion: These findings indicate
      that anti-NMDAR containing CSF impairs LTP at the A/C fiber-CA3 synapse, although
      there is substantial variation among CSF samples suggesting different epitopes
      among patient-derived antibodies. The differential inhibition of LTP at this
      synapse in contrast to the MF-CA3 synapse suggests the specificity and underlines
      the pathophysiological role of the NMDAR-antibody.

PMID- 30108499
TI  - Commentary: Metformin reverses TRAP1 mutation-associated alterations in
      mitochondrial function in Parkinson's disease.

PMID- 30108500
TI  - Clustering Analysis of FDG-PET Imaging in Primary Progressive Aphasia.
AB  - Background: Primary progressive aphasia (PPA) is a clinical syndrome
      characterized by the neurodegeneration of language brain systems. Three main
      clinical forms (non-fluent, semantic, and logopenic PPA) have been recognized,
      but applicability of the classification and the capacity to predict the
      underlying pathology is controversial. We aimed to study FDG-PET imaging data in
      a large consecutive case series of patients with PPA to cluster them into
      different subtypes according to regional brain metabolism. Methods: 122 FDG-PET
      imaging studies belonging to 91 PPA patients and 28 healthy controls were
      included. We developed a hierarchical agglomerative cluster analysis with Ward's
      linkage method, an unsupervised clustering algorithm. We conducted voxel-based
      brain mapping analysis to evaluate the patterns of hypometabolism of each
      identified cluster. Results: Cluster analysis confirmed the three current PPA
      variants, but the optimal number of clusters according to Davies-Bouldin index
      was 6 subtypes of PPA. This classification resulted from splitting non-fluent
      variant into three subtypes, while logopenic PPA was split into two subtypes.
      Voxel-brain mapping analysis displayed different patterns of hypometabolism for
      each PPA group. New subtypes also showed a different clinical course and were
      predictive of amyloid imaging results. Conclusion: Our study found that there are
      more than the three already recognized subtypes of PPA. These new subtypes were
      more predictive of clinical course and showed different neuroimaging patterns.
      Our results support the usefulness of FDG-PET in evaluating PPA, and the
      applicability of computational methods in the analysis of brain metabolism for
      improving the classification of neurodegenerative disorders.

PMID- 30108498
TI  - The Abeta Containing Brain Extracts Having Different Effects in Alzheimer's
      Disease Transgenic Caenorhabditis elegans and Mice.
AB  - Background: The deposition of beta-sheet rich amyloid in senile plaques is a
      pathological hallmark of Alzheimer's disease (AD), which is thought to cause
      neuronal dysfunction. Previous studies have strongly implicated that
      intracerebral infusion of brain extract containing aggregated beta-amyloid
      (Abeta) is able to induce cerebral amyloidosis thus causing neuronal damage and
      clinical abnormalities in rodents and nonhuman primates, which are reminiscent of
      a prion-like mechanism. Prion disease has been documented in cases of prion
      contaminated food consumption. Methods: We investigated whether cerebral
      transmission of Abeta was possible via oral administration of Abeta-rich brain
      extract in non-susceptible and susceptible host mice by immunohistochemistry,
      western blotting and behavior tests. Also brain extracts were supplied to AD
      transgenic Caenorhabditis elegans, and paralysis curve were conducted, following
      detection of Abeta amyloid. RNA sequencing of nematodes was applied then
      inhibitors for relevant dysregulated genes were used in the paralysis induction.
      Results: The oral treatment of AD brain extract or normal brain extract neither
      aggravated nor mitigated the Abeta load, glial activation or the abnormal
      behaviors in recipient Amyloid precursor protein/presenilin 1 (APP/PS1) mice.
      Whereas, a significant improvement of AD pathology was detected in worms treated
      with Abeta-rich or normal brain extracts, which was attributable to the heat
      sensitive components of brain extracts. Transcriptome sequencing of CL4176
      nematodes suggested that brain extracts could delay worm paralysis through
      multiple pathways, including ubiquitin mediated proteolysis and Transforming
      growth factor beta (TGF-beta) signaling pathway. Inhibitors of the ubiquitin
      proteasome system and the TGF-beta signaling pathway significantly blocked the
      suppressive effects of brain extracts on worm paralysis. Conclusions: Our results
      suggest that systemic transmissible mechanisms of prion proteopathy may not apply
      to beta amyloid, at least in terms of oral administration. However, brain
      extracts strongly ameliorated AD pathology in AD transgenic nematodes partially
      through TGF-beta signaling pathway and ubiquitin mediated proteolysis, which
      indicated that some natural endogenous components in the mammalian tissues could
      resist Abeta toxicity.

PMID- 30108501
TI  - Fisetin Inhibited Growth and Metastasis of Triple-Negative Breast Cancer by
      Reversing Epithelial-to-Mesenchymal Transition via PTEN/Akt/GSK3beta Signal
      Pathway.
AB  - Triple negative breast cancer (TNBC), characterized by its highly aggressive and
      metastatic features, is associated with poor prognosis and high mortality partly
      due to lack of effective treatment. Fisetin, a natural flavonoid compound, has
      been demonstrated to possess anti-cancer effects in various cancers. However, the
      effects and mechanisms of fisetin on metastasis of TNBC remain uncovered. In this
      study, we found that fisetin dose-dependently inhibited cell proliferation,
      migration and invasion in TNBC cell lines MDA-MB-231 and BT549 cells. In
      addition, fisetin reversed epithelial to mesenchymal transition (EMT) as
      evaluated by cell morphology and EMT markers in MDA-MB-231 and BT549 cells.
      Furthermore, fisetin suppressed phosphoinositol 3-kinase (PI3K)-Akt-GSK-3beta
      signaling pathway but upregulated the expression of PTEN mRNA and protein in a
      concentration-dependent manner. Further, silence of PTEN by siRNA abolished these
      benefits of fisetin on proliferation and metastasis of TNBCs. In vivo, using the
      metastatic breast cancer xenograft model bearing MDA-MB-231 cells, we found that
      fisetin dramatically inhibited growth of primary breast tumor and reduced lung
      metastasis, meanwhile, the expression of EMT molecules and PTEN/Akt/GSK-3beta in
      primary and metastatic tissues changed in the same way as those in vitro
      experiments. In conclusion, all these results indicated that fisetin could
      effectively suppress proliferation and metastasis of TNBC and reverse EMT
      process, which might be mediated by PTEN/Akt/GSK-3beta signaling pathway.

PMID- 30108502
TI  - Correction of Anemia in Chronic Kidney Disease With Angelica sinensis
      Polysaccharide via Restoring EPO Production and Improving Iron Availability.
AB  - Given the limited efficacy and potential disadvantages of erythropoiesis
      stimulating agents (ESAs) in treating anemia of chronic kidney disease (CKD), the
      development of better alternative therapies has become a priority. The primary
      purpose of this study is to investigate the effects of Angelica sinensis
      polysaccharide (ASP) and its underlying mechanism in the treatment of renal
      anemia. In the present study, we found that ASP could enhance hypoxic induction
      of EPO in Hep3B cells, with a mechanism that involved the stabilization of HIF
      2alpha protein. In parallel, ASP rescued the inhibition of EPO, induced by
      proinflammatory factor TNF-alpha through blocking GATA2 and NF-kappaB activation.
      In a rat model of adenine-induced anemia of CKD, oral administration of ASP
      corrected anemia and alleviated renal damage and inflammation. By increasing the
      accumulation of HIF-2alpha protein and reducing the expression of NF-kappaB and
      GATA2 as well as pro-inflammatory cytokines, ASP stimulated both renal and
      hepatic EPO production, and resulted in an elevation of serum EPO. The
      restoration of EPO production and EPOR mRNA expression with ASP treatment
      activated EPOR downstream JAK2/STAT5 and PI3K/Akt signaling, induced their target
      genes, such as Bcl-xL, Fam132b and Tfrc, and increased Bcl-2/Bax ratio in bone
      marrow-derived mononuclear cells of CKD rats. Furthermore, we found that ASP
      suppressed hepatic hepcidin expression, mobilized iron from spleen and liver and
      increased serum iron. These findings demonstrate that ASP elicits anti-anemic
      action by restoring EPO production and improving iron availability in the setting
      of CKD in rats.

PMID- 30108503
TI  - In Vivo Non-radioactive Assessment of mGlu5 Receptor-Activated
      Polyphosphoinositide Hydrolysis in Response to Systemic Administration of a
      Positive Allosteric Modulator.
AB  - mGlu5 receptor-mediated polyphosphoinositide (PI) hydrolysis is classically
      measured by determining the amount of radioactivity incorporated in
      inositolmonophosphate (InsP) after labeling of membrane phospholipids with
      radioactive inositol. Although this method is historically linked to the study of
      mGlu receptors, it is inappropriate for the assessment of mGlu5 receptor
      signaling in vivo. Using a new ELISA kit we showed that systemic treatment with
      the selective positive allosteric modulator (PAM) of mGlu5 receptors VU0360172
      enhanced InsP formation in different brain regions of CD1 or C57Black mice. The
      action of VU0360172 was sensitive to the mGlu5 receptor, negative allosteric
      modulator (NAM), MTEP, and was abolished in mice lacking mGlu5 receptors. In
      addition, we could demonstrate that endogenous activation of mGlu5 receptors
      largely accounted for the basal PI hydrolysis particularly in the prefrontal
      cortex. This method offers opportunity for investigation of mGlu5 receptor
      signaling in physiology and pathology, and could be used for the functional
      screening of mGlu5 receptor PAMs in living animals.

PMID- 30108504
TI  - Nrf2 Activation Provides Atheroprotection in Diabetic Mice Through Concerted
      Upregulation of Antioxidant, Anti-inflammatory, and Autophagy Mechanisms.
AB  - Interactive relationships between metabolism, inflammation, oxidative stress, and
      autophagy in the vascular system play a key role in the pathogenesis of diabetic
      cardiovascular disease. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a
      stress-sensitive guarantor of cellular homeostasis, which cytoprotective
      contributions extend beyond the antioxidant defense. We investigated the
      beneficial effects and underlying mechanisms of the Nrf2 inducer tert-butyl
      hydroquinone (tBHQ) on diabetes-driven atherosclerosis. In the experimental model
      of streptozotocin-induced diabetes in apolipoprotein E-deficient mice, treatment
      with tBHQ increased Nrf2 activity in macrophages and vascular smooth muscle cells
      within atherosclerotic lesions. Moreover, tBHQ significantly decreased the size,
      extension and lipid content of atheroma plaques, and attenuated inflammation by
      reducing lesional macrophages (total number and M1/M2 phenotype balance), foam
      cell size and chemokine expression. Atheroprotection was accompanied by both
      systemic and local antioxidant effects, characterized by lower levels of
      superoxide anion and oxidative DNA marker 8-hydroxy-2'-deoxyguanosine, reduced
      expression of NADPH oxidase subunits, and increased antioxidant capacity.
      Interestingly, tBHQ treatment upregulated the gene and protein expression of
      autophagy-related molecules and also enhanced autophagic flux in diabetic mouse
      aorta. In vitro, Nrf2 activation by tBHQ suppressed cytokine-induced expression
      of pro-inflammatory and oxidative stress genes, altered macrophage phenotypes,
      and promoted autophagic activity. Our results reinforce pharmacological Nrf2
      activation as a promising atheroprotective approach in diabetes, according to the
      plethora of cytoprotective mechanisms involved in the resolution of inflammation
      and oxidative stress, and restoring autophagy.

PMID- 30108506
TI  - Lico A Causes ER Stress and Apoptosis via Up-Regulating miR-144-3p in Human Lung
      Cancer Cell Line H292.
AB  - During our study on the bioactivities of natural flavonoids, we found that the
      total flavonoids (TFs) and the main constituent of it, licochalcone A (lico A),
      activated unfolded protein response (UPR) and induced autophagy and thereby
      apoptosis in H292 cells. MicroRNAs, such as the tumor repressor miR-144-3p, were
      reported to be differentially expressed in lung cancer cells and were linked to
      ER stress, autophagy, and apoptosis. However, the underlying miRNA-based
      mechanism for lico A modulating proliferation, autophagy and apoptosis in lung
      cancer cells is elusive. In this study, we found that miR-144-3p was down
      regulated in H292 cells comparing to normal embryonic lung cells WI-38, and lico
      A (10 MUM) could increase miR-144-3p level in H292 cells. Knockdown of miR-144-3p
      significantly abrogated the apoptosis and proliferation-inhibiting effects of
      lico A, and lico A could enhance the proliferation-inhibiting effect and
      apoptosis induced by miR-144-3p overexpression. Moreover, overexpression miR-144
      3p could induce ER stress by down-regulating Nrf2, and lico A enhanced the Nrf2
      down-regulation caused by miR-144-3p overexpression. Co-transfection experiments
      showed that lico A potentially increased the dicing of pre-miR-144 so as to
      increase the mature miR-144-3p level. Interestingly, high level of lico A (40
      MUM) up-regulated CHOP protein, but failed to increase the downstream genes
      levels of CHOP, including Bim and Bcl-2 in H292 cells. Docking studies indicated
      that CHOP-mediated pathway was potentially blocked by high dose of lico A. Our
      results suggested that lico A could cause UPR, autophagy and apoptosis, and the
      underlying mechanism involved up-regulation of miR-144-3p, and increased lico A
      level would also increase the potential for lico A inhibiting CHOP-dependent
      apoptosis in H292 cells.

PMID- 30108505
TI  - Investigating the Mechanism of Action of Diketopiperazines Inhibitors of the
      Burkholderia cenocepacia Quorum Sensing Synthase CepI: A Site-Directed
      Mutagenesis Study.
AB  - Quorum sensing (QS) is a bacterial intercellular communication process which
      controls the production of major virulence factors, such as proteases,
      siderophores, and toxins, as well as biofilm formation. Since the inhibition of
      this pathway reduces bacterial virulence, QS is considered a valuable candidate
      drug target, particularly for the treatment of opportunistic infections, such as
      those caused by Burkholderia cenocepacia in cystic fibrosis patients.
      Diketopiperazine inhibitors of the acyl homoserine lactone synthase CepI have
      been recently described. These compounds are able to impair the ability of B.
      cenocepacia to produce proteases, siderophores, and to form biofilm, being also
      active in a Caenorhabditis elegans infection model. However, the precise
      mechanism of action of the compounds, as well as their effect on the cell
      metabolism, fundamental for candidate drug optimization, are still not completely
      defined. Here, we performed a proteomic analysis of B. cenocepacia cells treated
      with one of these inhibitors, and compared it with a cepI deleted strain. Our
      results demonstrate that the effects of the compound are similar to the deletion
      of cepI, clearly confirming that these molecules function as inhibitors of the
      acyl homoserine lactone synthase. Moreover, to deepen our knowledge about the
      binding mechanisms of the compound to CepI, we exploited previously published in
      silico structural insights about this enzyme structure and validated different
      candidate binding pockets on the enzyme surface using site-directed mutagenesis
      and biochemical analyses. Our experiments identified a region near the predicted
      S-adenosylmethionine binding site critically involved in interactions with the
      inhibitor. These results could be useful for future structure-based optimization
      of these CepI inhibitors.

PMID- 30108508
TI  - Influence of the KCNQ1 S140G Mutation on Human Ventricular Arrhythmogenesis and
      Pumping Performance: Simulation Study.
AB  - The KCNQ1 S140G mutation, which is involved in IKs current, affects atrial
      fibrillation. However, little is known about its effect on the mechanical
      behavior of the heart. Therefore, we assessed the influence of the KCNQ1 S140G
      mutation on ventricular electrophysiological stability and mechanical pumping
      performance using a multi-scale model of cardiac electromechanics. An image-based
      electromechanical model was used to assess the effect on electrical propagation
      and arrhythmogenesis of the KCNQ1 S140G mutation. In addition, it was used to
      compare the mechanical response under the wild-type (WT) and S140G mutation
      conditions. The intracellular calcium transient obtained from the
      electrophysiological model was applied as an input parameter to a mechanical
      model to implement excitation-contraction coupling. The IKs current equation was
      modified to account for expression of the KCNQ1 S140G mutation, and it included a
      scaling factor (phi) for mutant expressivity. The WT and S140G mutation
      conditions were compared at the single-cell and three-dimensional (3D) tissue
      levels. The action potential duration (APD) was reduced by 60% by the augmented
      IKs current under the S140G mutation condition, which resulted in shorter QT
      interval. This reduced the 3D sinus rhythm wavelength by 60% and the sustained re
      entry by 56%. However, pumping efficiency of mutant ventricles was superior in
      sinus rhythm condition. In addition, the shortened wavelength in cardiac tissue
      allowed a re-entrant circuit to form and increased the probability of sustaining
      ventricular tachycardia and ventricular fibrillation. In contrast, under the WT
      condition, a normal wavelength (20.8 cm) was unlikely to initiate and sustain re
      entry in the cardiac tissue. Subsequently, the S140G mutant ventricles developed
      a higher dominant frequency distribution range (2.0-5.3 Hz) than the WT condition
      (2.8-3.7 Hz). In addition, stroke volume of mutant ventricles was reduced by 65%
      in sustained re-entry compared to the WT condition. In conclusion, signs of the
      S140G mutation might be difficult to identify in sinus rhythm even though the
      mutant ventricles show shortened QT interval. This suggests that the KCNQ1 S140G
      mutation increases the risk of death by sudden cardiac arrest. In addition, the
      KCNQ1 S140G mutation can induce ventricular arrhythmia and lessen ventricular
      contractility under re-entrant conditions.

PMID- 30108507
TI  - Vascular Smooth Muscle Contractile Function Declines With Age in Skeletal Muscle
      Feed Arteries.
AB  - Aging induces a progressive decline in vasoconstrictor responses in central and
      peripheral arteries. This study investigated the hypothesis that vascular smooth
      muscle (VSM) contractile function declines with age in soleus muscle feed
      arteries (SFA). Contractile function of cannulated SFA isolated from young (4
      months) and old (24 months) Fischer 344 rats was assessed by measuring
      constrictor responses of denuded (endothelium removed) SFA to norepinephrine
      (NE), phenylephrine (PE), and angiotensin II (Ang II). In addition, we
      investigated the role of RhoA signaling in modulation of VSM contractile
      function. Structural and functional characteristics of VSM cells were evaluated
      by fluorescence imaging and atomic force microscopy (AFM). Results indicated that
      constrictor responses to PE and Ang II were significantly impaired in old SFA,
      whereas constrictor responses to NE were preserved. In the presence of a Rho
      kinase inhibitor (Y27632), constrictor responses to NE, Ang II, and PE were
      significantly reduced in young and old SFA. In addition, the age-group difference
      in constrictor responses to Ang II was eliminated. ROCK1 and ROCK2 content was
      similar in young and old VSM cells, whereas pROCK1 and pROCK2 were significantly
      elevated in old VSM cells. Aging was associated with a reduction in smooth muscle
      alpha-actin stress fibers and recruitment of proteins to cell-matrix adhesions.
      Old VSM cells presented an increase in integrin adhesion to the matrix and smooth
      muscle gamma-actin fibers that was associated with increased cell stiffness. In
      conclusion, our results indicate that VSM contractile function declined with age
      in SFA. The decrement in contractile function was mediated in part by RhoA/ROCK
      signaling. Upregulation of pROCK in old VSM cells was not able to rescue
      contractility in old SFA. Collectively, these results indicate that changes at
      the VSM cell level play a central role in the reduced contractile function of
      aged SFA.

PMID- 30108509
TI  - Cisatracurium Retards Cell Migration and Invasion Upon Upregulation of p53 and
      Inhibits the Aggressiveness of Colorectal Cancer.
AB  - Colorectal cancer (CRC) is reported to be the third and fourth, most diagnosed
      and cause of cancer associated deaths respectively. In 2012 for instance, about
      1.4 million new cases were reported, and approximately 700,000 deaths recorded.
      Survival from CRC is dependent on the stage at which it is diagnosed coupled with
      appropriate surgical and medical intervention. Cisatracurium is widely used for
      skeletal muscle relaxation during abdominal surgeries, including bowel and colon
      surgeries. Recent studies reported that cisatracurium inhibits progression of
      human cancer cells, however, the mechanisms leading to the inhibition are yet to
      be completely understood. To elucidate mechanisms resulting particularly in tumor
      cell growth and metastasis, we developed ex vivo and in in vivo xenograft models
      of CRC. Cisatracurium caused upregulation of p53 and its down-stream genes and
      proteins known to regulate proliferation and metastasis in vitro and in vivo.
      Genomic analyses of CRC following cisatracurium treatment revealed moderate to
      high DNA damage, while functional analyses demonstrated significant tumor cells
      growth regression, as well as repression of migration and invasion. Importantly,
      cisatracurium increased E-Cadherin and CALD-1 but decreased SNAI-1 and SLUG
      levels in vitro and in vivo. Together, the findings demonstrate that elevation of
      p53 upon cisatracurium-induced genomic injury, represent a potential mechanism by
      which cisatracurium result in the suppression of CRC progression and metastasis.

PMID- 30108510
TI  - In Vivo Calcium Imaging of Cardiomyocytes in the Beating Mouse Heart With
      Multiphoton Microscopy.
AB  - Background: Understanding the microscopic dynamics of the beating heart has been
      challenging due to the technical nature of imaging with micrometer resolution
      while the heart moves. The development of multiphoton microscopy has made in
      vivo, cell-resolved measurements of calcium dynamics and vascular function
      possible in motionless organs such as the brain. In heart, however, studies of in
      vivo interactions between cells and the native microenvironment are behind other
      organ systems. Our goal was to develop methods for intravital imaging of cardiac
      structural and calcium dynamics with microscopic resolution. Methods: Ventilated
      mice expressing GCaMP6f, a genetically encoded calcium indicator, received a
      thoracotomy to provide optical access to the heart. Vasculature was labeled with
      an injection of dextran-labeled dye. The heart was partially stabilized by a
      titanium probe with a glass window. Images were acquired at 30 frames per second
      with spontaneous heartbeat and continuously running, ventilated breathing. The
      data were reconstructed into three-dimensional volumes showing tissue structure,
      vasculature, and GCaMP6f signal in cardiomyocytes as a function of both the
      cardiac and respiratory cycle. Results: We demonstrated the capability to
      simultaneously measure calcium transients, vessel size, and tissue displacement
      in three dimensions with micrometer resolution. Reconstruction at various
      combinations of cardiac and respiratory phase enabled measurement of regional and
      single-cell cardiomyocyte calcium transients (GCaMP6f fluorescence). GCaMP6f
      fluorescence transients in individual, aberrantly firing cardiomyocytes were also
      quantified. Comparisons of calcium dynamics (rise-time and tau) at varying
      positions within the ventricle wall showed no significant depth dependence.
      Conclusion: This method enables studies of coupling between contraction and
      excitation during physiological blood perfusion and breathing at high
      spatiotemporal resolution. These capabilities could lead to a new understanding
      of normal and disease function of cardiac cells.

PMID- 30108511
TI  - Exergaming in a Moving Virtual World to Train Vestibular Functions and Gait; a
      Proof-of-Concept-Study With Older Adults.
AB  - Background: The use of Exergames designed to improve physical and cognitive
      functioning is relatively new in rehabilitation. Exergaming allows the training
      of skills, the handling of tools, and procedures; however, often, the potential
      of these aspects are not assessed before they are adopted in clinical settings.
      This study aimed at exploring the effects of exergaming on vestibular functions
      and gait in healthy community dwelling older adults using a proof-of-concept
      study design registered under ClinicalTrials.gov NCT03160352. Methods: A pre-test
      post-test one-group study design comprising 10 older adults (mean age of 73.5 +/-
      7.6 years, four males) investigated the feasibility of eight exergaming training
      sessions (for 160 min) and the effects on dynamic visual acuity (DVA), functional
      gait assessment (FGA), and extended timed get-up-and-go (ETGUG). The simulator
      sickness questionnaire (SSQ) and the game scores were evaluated for the
      feasibility of the intervention. Wilcoxon test and Cohen's d (d) were chosen to
      test for differences and for effect size estimation. Results: Exergaming led to a
      significantly improved DVA (z = -2.50, p = 0.01, d = 1.35) with improvements in 9
      out of 10 participants. In addition, the FGA significantly improved with a large
      effect size (z = -2.25, p = 0.02, d = 1.17). Specifically, component tasks such
      as walking with horizontal head turns (p = 0.03), gait with a narrow base of
      support (p = 0.03), ambulating backward (p = 0.05) significantly improved. The
      ETGUG component task Gait initiation significantly improved (p = 0.04). No change
      was found in gait speed and SSQ. The game scores of the participants improved
      continuously during the course of the intervention for every game. Discussion:
      This proof-of-concept study suggests that the use of exergaming that requires
      active stepping movements and that contains moving game projection is feasible
      and facilitates gaze stability during head movements in healthy community
      dwelling older adults. Aspects of functional gait and gait initiation also
      improved. Future research aimed at testing this exergaming intervention in
      patients suffering from vestibular impairments is warranted.

PMID- 30108512
TI  - Are Nutrition-Related Knowledge and Attitudes Reflected in Lifestyle and Health
      Among Elderly People? A Study Across Five European Countries.
AB  - Background: Nutrition-related knowledge (NRK) and nutrition-related attitudes
      (NRAs) are necessary for dietary changes toward healthier dietary patterns. In
      turn, healthier dietary patterns can be beneficial in maintaining health of older
      adults. Therefore, the aim of this cross-sectional study was to investigate
      whether NRK and NRAs were associated with lifestyle and health features among
      older adults (65+ years) from five European countries (France, Italy, Poland, the
      Netherlands and United Kingdom). Methods: Within the European project NU-AGE,
      1,144 healthy elderly volunteers (65-79 years) were randomly assigned to two
      groups: intervention (NU-AGE diet) or control. After 1-year of follow-up, both
      NRK and NRAs were assessed during exit interviews, in combination with a number
      of lifestyle and health variables (e.g., physical activity, smoking, alcohol use,
      BMI, self-assessed health status). Multivariable linear regression models were
      used in data analysis. Results: In the NU-AGE study sample, good NRK was
      associated with lower BMI and higher physical activity. More positive NRAs were
      related to lower BMI and self-reported very good or good appetite. Moreover, both
      NRK and NRAs were associated with some socio-economic determinants, like
      financial situation, age, education, living area (for NRK), and country (for
      NRAs). Participants in the intervention group showed a better NRK (beta = 0.367
      [95% CI: 0.117; 0.617], p = 0.004) and more positive NRAs (beta = 0.838 [95% CI:
      0.318; 1.358], p = 0.002) than those in the control group. Higher self-evaluated
      knowledge was also significantly related to more positive NRAs (p < 0.001). The
      most popular sources of nutrition information were food labels, books and
      magazines on health, the dietitian and the doctor's office, although their
      importance varied significantly among countries, and, to a lesser extent, between
      women and men and between intervention and control group. Conclusion: Higher NRK
      and NRA scores were associated with lower BMI and higher physical activity level.
      Therefore, a good nutrition-related knowledge and positive nutrition-related
      attitudes can strongly and positively influence the health status and quality of
      life among the older population. These results offer a great opportunity for
      policy makers to implement educational programs in order to counteract the
      epidemic of obesity and to improve the health span of European population.

PMID- 30108513
TI  - Effects of Inducible Nitric Oxide Synthase Inhibition on Cardiovascular Risk of
      Adult Endotoxemic Female Rats: Role of Estrogen.
AB  - Aim: Autonomic modulation responds to ovarian hormones and estrogen increases
      nitric oxide bioavailability. Also, females have minor susceptibility to sepsis
      and a higher survival rate. However, few studies have evaluated the role of
      estrogen in cardiovascular, autonomic, and oxidative parameters during initial
      endotoxemia and under inducible nitric oxide synthase (iNOS) inhibition in female
      rats. Methods: Female wistar rats were subjected to ovariectomy and divided into
      three groups: OVX (ovariectomized), OVX+E (OVX plus daily estradiol) and SHAM
      (false surgery). After 8 weeks, mean arterial pressure (MAP) and heart rate (HR)
      were recorded in non-anesthetized catheterized rats, before and after intravenous
      LPS injection, preceded by S-methylisothiourea sulfate (SMT) injection, or
      sterile saline. Cardiovascular recordings underwent spectral analysis for
      evaluation of autonomic modulation. Two hours after LPS, plasma was collected to
      assess total radical-trapping antioxidant (TRAP), nitrite levels (NO2),
      lipoperoxidation (LOOH), and paraoxonase 1 (PON1) activity. Results: Two hours
      after LPS, females treated with SMT presented a decrease of MAP, when compared to
      saline-LPS groups. At this same time, all SMT+LPS groups presented an increase of
      sympathetic and a decrease of parasympathetic modulation of HR. Two hours after
      saline+LPS, OVX presented decreased total radical-trapping antioxidant (TRAP)
      compared to SHAM. When treated with SMT+LPS, OVX did not altered TRAP, while
      estradiol reduced LOOH levels. Conclusion: iNOS would be responsible for
      sympathetic inhibition and consumption of antioxidant reserves of females during
      endotoxemia, since iNOS is inhibited, treatment with estradiol could be
      protective in inflammatory challenges.

PMID- 30108514
TI  - Epigenetic Alterations in Anesthesia-Induced Neurotoxicity in the Developing
      Brain.
AB  - Before birth and early in life, the developing brain is particularly sensitive to
      environmental and pharmacological influences. Increasing experimental evidence
      suggests that an association exists between exposure to anesthesia during a
      vulnerable period of brain development and subsequent poor neurodevelopmental
      outcomes. However, the mechanisms underlying this association are not fully
      understood. Epigenetics, broadly defined as the regulation of gene expression
      without alterations of DNA sequence, has become a field of tremendous interest in
      neuroscience. In recent years, a growing body of literature suggests that
      anesthesia-induced long-term changes in gene transcription and functional
      deficits in learning and behavior later in life are mediated via epigenetic
      modifications. This brief review provides an overview of epigenetic mechanisms
      and highlights the emerging roles played by epigenetic dysfunctions in the
      processes of anesthesia-induced neurotoxicity in the developing brain. Epigenetic
      targeting of DNA methyltransferases and/or histone deacetylases may have some
      therapeutic value. Epigenetics may lead to the identification of novel markers
      that contribute toward considerable translational significance in the field of
      neuroprotection.

PMID- 30108515
TI  - Microgravity-Induced Alterations of Inflammation-Related Mechanotransduction in
      Endothelial Cells on Board SJ-10 Satellite.
AB  - Endothelial cells (ECs) are mechanosensitive cells undergoing morphological and
      functional changes in space. Ground-based study has provided a body of evidences
      about how ECs can respond to the effect of simulated microgravity, however, these
      results need to be confirmed by spaceflight experiments in real microgravity. In
      this work, we cultured EA.hy926 ECs on board the SJ-10 Recoverable Scientific
      Satellite for 3 and 10 days, and analyzed the effects of space microgravity on
      the ECs. Space microgravity suppressed the glucose metabolism, modulated the
      expression of cellular adhesive molecules such as ICAM-1, VCAM-1, and CD44, and
      depressed the pro-angiogenesis and pro-inflammation cytokine secretion.
      Meanwhile, it also induced the depolymerization of actin filaments and
      microtubules, promoted the vimentin accumulation, restrained the collagen I and
      fibronectin deposition, regulated the mechanotransduction through focal adhesion
      kinase and Rho GTPases, and enhanced the exosome-mediated mRNA transfer. Unlike
      the effect of simulated microgravity, neither three-dimensional growth nor
      enhanced nitric oxide production was observed in our experimental settings. This
      work furthers the understandings in the effects and mechanisms of space
      microgravity on ECs, and provides useful information for future spaceflight
      experimental design.

PMID- 30108518
TI  - Slipstreaming in Gravity Powered Sports: Application to Racing Strategy in Ski
      Cross.
AB  - The principles of slipstreaming or drafting are very well known in muscle-powered
      sports, but unknown in gravity-powered sports. Typical examples of gravity
      powered sports, where several athletes are racing against each other, are ski
      cross and snowboard-cross. The aim of this research is to investigate the
      effectiveness and practical applicability of slipstreaming in ski-cross. A glide
      model consisting of leading and trailing skiers was developed and used with
      existing aerodynamic drag and lift data sets from wind tunnel tests. Different
      scenarios were tested as to their effect on slipstreaming, such as variation of
      speed, skiers' mass, slope angle, air density, and racing posture (high/low
      tucked position). The higher the trailing skier's inertial force and acceleration
      is compared to the leading one, the quicker the trailing skier can catch up.
      Making more ground up on the racing track is related to higher speed, less body
      mass (of both skiers), flatter slope angle, denser air, and higher racing posture
      (high tucked position of both skiers). The glide model presented in this research
      can be used in the future for testing of slope track design, provided that
      precise dimensions of terrain features are available.

PMID- 30108516
TI  - Inhalation of Hydrogen Attenuates Progression of Chronic Heart Failure via
      Suppression of Oxidative Stress and P53 Related to Apoptosis Pathway in Rats.
AB  - Background: Continuous damage from oxidative stress and apoptosis are the
      important mechanisms that facilitate chronic heart failure (CHF). Molecular
      hydrogen (H2) has potentiality in the aspects of anti-oxidation. The objectives
      of this study were to investigate the possible mechanism of H2 inhalation in
      delaying the progress of CHF. Methods and Results: A total of 60 Sprague-Dawley
      (SD) rats were randomly divided into four groups: Sham, Sham treated with H2, CHF
      and CHF treated with H2. Rats from CHF and CHF treated with H2 groups were
      injected isoprenaline subcutaneously to establish the rat CHF model. One month
      later, the rat with CHF was identified by the echocardiography. After inhalation
      of H2, cardiac function was improved vs. CHF (p < 0.05), whereas oxidative stress
      damage and apoptosis were significantly attenuated (p < 0.05). In this study, the
      mild oxidative stress was induced in primary cardiomyocytes of rats, and H2
      treatments significantly reduced oxidative stress damage and apoptosis in
      cardiomyocytes (p < 0.05 or p < 0.01). Finally, as a pivotal transcription factor
      in reactive oxygen species (ROS)-apoptosis signaling pathway, the expression and
      phosphorylation of p53 were significantly reduced by H2 treatment in this rat
      model and H9c2 cells (p < 0.05 or p < 0.01). Conclusion: As a safe antioxidant,
      molecular hydrogen mitigates the progression of CHF via inhibiting apoptosis
      modulated by p53. Therefore, from the translational point of view and
      speculation, H2 is equipped with potential therapeutic application as a novel
      antioxidant in protecting CHF in the future.

PMID- 30108517
TI  - Gender-Specific Cardiovascular Reactions to +Gz Interval Training on a Short Arm
      Human Centrifuge.
AB  - Cardiovascular deconditioning occurs in astronauts during microgravity exposure,
      and may lead to post-flight orthostatic intolerance, which is more prevalent in
      women than men. Intermittent artificial gravity is a potential countermeasure,
      which can effectively train the cardiovascular mechanisms responsible for
      maintaining orthostatic integrity. Since cardiovascular responses may differ
      between women and men during gravitational challenges, information regarding
      gender specific responses during intermittent artificial gravity exposure plays a
      crucial role in countermeasure strategies. This study implemented a +Gz interval
      training protocol using a ground based short arm human centrifuge, in order to
      assess its effectiveness in stimulating the components of orthostatic integrity,
      such as diastolic blood pressure, heart rate and vascular resistance amongst both
      genders. Twenty-eight participants (12 men/16 women) underwent a two-round graded
      +1/2/1 Gz profile, with each +Gz phase lasting 4 min. Cardiovascular parameters
      from each phase (averaged last 60 sec) were analyzed for significant changes with
      respect to baseline values. Twelve men and eleven women completed the session
      without interruption, while five women experienced an orthostatic event. These
      women had a significantly greater height and baseline mean arterial pressure than
      their counterparts. Throughout the +Gz interval session, women who completed the
      session exhibited significant increases in heart rate and systemic vascular
      resistance index throughout all +Gz phases, while exhibiting increases in
      diastolic blood pressure during several +Gz phases. Men expressed significant
      increases from baseline in diastolic blood pressure throughout the session with
      heart rate increases during the +2Gz phases, while no significant changes in
      vascular resistance were recorded. Furthermore, women exhibited non-significantly
      higher heart rates over men during all phases of +Gz. Based on these findings,
      this protocol proved to consistently stimulate the cardiovascular systems
      involved in orthostatic integrity to a larger extent amongst women than men. Thus
      the +Gz gradients used for this interval protocol may be beneficial for women as
      a countermeasure against microgravity induced cardiovascular deconditioning,
      whereas men may require higher +Gz gradients. Lastly, this study indicates that
      gender specific cardiovascular reactions are apparent during graded +Gz exposure
      while no significant differences regarding cardiovascular responses were found
      between women and men during intermittent artificial gravity training.

PMID- 30108520
TI  - Regular Muscle Electrical Stimulation Could Act Favorably On Bone Mineral Density
      in Healthy Aged Subjects.

PMID- 30108519
TI  - A "Blood Relationship" Between the Overlooked Minimum Lactate Equivalent and
      Maximal Lactate Steady State in Trained Runners. Back to the Old Days?
AB  - Maximal Lactate Steady State (MLSS) and Lactate Threshold (LT) are
      physiologically-related and fundamental concepts within the sports and exercise
      sciences. Literature supporting their relationship, however, is scarce. Among the
      recognized LTs, we were particularly interested in the disused "Minimum Lactate
      Equivalent" (LEmin), first described in the early 1980s. We hypothesized that
      velocity at LT, conceptually comprehended as in the old days (LEmin), could
      predict velocity at MLSS (VMLSS) more accurate than some other blood lactate
      related thresholds (BLRTs) routinely used nowadays by many sport science
      practitioners. Thirteen male endurance-trained [VMLSS 15.0 +/- 1.1 km.h-1;
      maximal oxygen uptake ( V.O2max ) 67.6 +/- 4.1 ml.kg-1.min-1] homogeneous
      (coefficient of variation: ~7%) runners conducted 1) a submaximal discontinuous
      incremental running test to determine several BLRTs followed by a maximal ramp
      incremental running test for V.O2max  determination, and 2) several (4-5)
      constant velocity running tests to determine VMLSS with a precision of 0.20 km.h
      1. Determined BLRTs include LEmin and LEmin-related LEmin plus 1 (LEmin+1mM) and
      1.5 mmol.L-1 (LEmin+1.5mM), along with well-established BLRTs such as
      conventionally-calculated LT, Dmax and fixed blood lactate concentration
      thresholds. LEmin did not differ from LT (P = 0.71; ES: 0.08) and was 27% lower
      than MLSS (P < 0.001; ES: 3.54). LEmin+1mM was not different from MLSS (P = 0.47;
      ES: 0.09). LEmin was the best predictor of VMLSS (r = 0.91; P < 0.001; SEE = 0.47
      km.h-1), followed by LEmin+1mM (r = 0.86; P < 0.001; SEE = 0.58 km.h-1) and
      LEmin+1.5mM (r = 0.84; P < 0.001; SEE = 0.86 km.h-1). There was no statistical
      difference between MLSS and estimated MLSS using LEmin prediction formula (P =
      0.99; ES: 0.001). Mean bias and limits of agreement were 0.00 +/- 0.45 km.h-1 and
      +/-0.89 km.h-1. Additionally, LEmin, LEmin+1mM and LEmin+1.5mM were the best
      predictors of V.O2max (r = 0.72-0.79; P < 0.001). These results support LEmin, an
      objective submaximal overlooked and underused BLRT, to be one of the best single
      MLSS predictors in endurance trained runners. Our study advocates factors
      controlling LEmin to be shared, at least partly, with those controlling MLSS.

PMID- 30108521
TI  - Combining Chronic Ischemic Preconditioning and Inspiratory Muscle Warm-Up to
      Enhance On-Ice Time-Trial Performance in Elite Speed Skaters.
AB  - Elite athletes in varied sports typically combine ergogenic strategies in the
      hope of enhancing physiological responses and competitive performance, but the
      scientific evidence for such practices is very scarce. The peculiar
      characteristics of speed skating contribute to impede blood flow and exacerbate
      deoxygenation in the lower limbs (especially the right leg). We investigated
      whether combining preconditioning strategies could modify muscular oxygenation
      and improve performance in that sport. Using a randomized, single-blind, placebo
      controlled, crossover design, seven male elite long-track speed skaters performed
      on-ice 600-m time trials, preceded by either a combination of preconditioning
      strategies (COMBO) or a placebo condition (SHAM). COMBO involved performing
      remote ischemic preconditioning (RIPC) of the upper limbs (3 * 5-min compression
      at 180 mmHg and 5-min reperfusion) over 3 days (including an acute treatment
      before trials), with the addition of an inspiratory muscle warm-up [IMW: 2 * 30
      inspirations at 40% maximal inspiratory pressure (MIP)] on the day of testing.
      SHAM followed the same protocol with lower intensities (10 mmHg for RIPC and 15%
      MIP). Changes in tissue saturation index (TSI), oxyhemoglobin-oxymyoglobin
      ([O2HbMb]), deoxyhemoglobin-deoxymyoglobin ([HHbMb]), and total hemoglobin
      myoglobin ([THbMb]) in the right vastus lateralis muscle were monitored by near
      infrared spectroscopy (NIRS). Differences between COMBO and SHAM were analyzed
      using Cohen's effect size (ES) and magnitude-based inferences. Compared with
      SHAM, COMBO had no worthwhile effect on performance time while mean Delta[HHbMb]
      (2.7%, ES 0.48; -0.07, 1.03) and peak Delta[HHbMb] (1.8%, ES 0.23; -0.10, 0.57)
      were respectively likely and possibly higher in the last section of the race.
      These results indicate that combining ischemic preconditioning and IMW has no
      practical ergogenic impact on 600-m speed-skating performance in elite skaters.
      The low-sitting position in this sport might render difficult enhancing these
      physiological responses.

PMID- 30108522
TI  - The Dominant Role of Visual Motion Cues in Bumblebee Flight Control Revealed
      Through Virtual Reality.
AB  - Flying bees make extensive use of optic flow: the apparent motion in the visual
      scene generated by their own movement. Much of what is known about bees' visually
      guided flight comes from experiments employing real physical objects, which
      constrains the types of cues that can be presented. Here we implement a virtual
      reality system allowing us to create the visual illusion of objects in 3D space.
      We trained bumblebees, Bombus ignitus, to feed from a static target displayed on
      the floor of a flight arena, and then observed their responses to various
      interposing virtual objects. When a virtual floor was presented above the
      physical floor, bees were reluctant to descend through it, indicating that they
      perceived the virtual floor as a real surface. To reach a target at ground level,
      they flew through a hole in a virtual surface above the ground, and around an
      elevated virtual platform, despite receiving no reward for avoiding the virtual
      obstacles. These behaviors persisted even when the target was made
      (unrealistically) visible through the obstructing object. Finally, we challenged
      the bees with physically impossible ambiguous stimuli, which give conflicting
      motion and occlusion cues. In such cases, they behaved in accordance with the
      motion information, seemingly ignoring occlusion.

PMID- 30108524
TI  - Genome-Wide Identification, Characterization and Expression Analyses of Heat
      Shock Protein-Related Genes in a Highly Invasive Ascidian Ciona savignyi.
AB  - Biological response to rapid changing environments is an outstanding research
      question in ecology and evolution. Biological invasions provide excellent
      "natural" experiments to study such a complex response process, as invaders often
      encounter rapidly changing environments during biological invasions. The
      regulation of heat shock proteins (Hsp) is a common pathway responsible for
      various environmental stresses; however, the comprehensive study on Hsp system
      across the whole genome and potential roles in determining invasion success are
      still largely unexplored. Here, we used a marine invasive model ascidian, Ciona
      savignyi, to investigate transcriptional response of Hsp-related genes to harsh
      environments. We identified 32 genes, including three Hsp20, six Hsp40, ten
      Hsp60, eight Hsp70, three Hsp90, one Hsp100, and one heat shock transcription
      factor (Hsf), across the whole genome of C. savignyi. We further characterized
      gene structure and protein motifs, and identified potential heat shock elements
      (HSEs) in promoters of Hsp genes. The expression analysis showed that most Hsp
      genes, but not all, were involved in transcriptional response to temperature and
      salinity challenges in a duration- and stress-specific pattern, and the maximum
      amplitude of induction occurred in Hsp70-4 after 1-h of high temperature
      treatment. However, the Hsf gene was scarcely induced and limited interactions
      were predicted between Hsp and Hsf genes. Our study provide the first systematic
      genome-wide analysis of Hsp and Hsf family in the marine invasive model ascidian,
      and our results are expected to dissect Hsp-based molecular mechanisms
      responsible for extreme environmental adaptation using Ciona as a model system.

PMID- 30108523
TI  - Molecular Mechanisms of Metformin for Diabetes and Cancer Treatment.
AB  - Metformin has been the first-line drug treatment for hyperglycemia and insulin
      resistance for over 50 years. However, the molecular basis of its therapeutic
      role remained incompletely understood. Recent advances demonstrate that metformin
      could exert its glucose-lowering effect by multiple mechanisms, including
      activation of 5'-AMP-activated protein kinase, decreasing production of cyclic
      AMP, suppressing mitochondrial complex I of the electron transport chain,
      targeting glycerophosphate dehydrogenase, and altering the gut microbiome. In
      addition, epidemiological and clinical observation studies suggest that metformin
      reduced cancer risk in patients with type 2 diabetes and improved survival
      outcome of human cancers. Experimental studies have shown that this drug can
      inhibit cancer cell viability, growth, and proliferation through inhibiting
      mTORC1 signaling and mitochondrial complex I, suggesting that it may be a
      promising drug candidate for malignancy. Here, we summarize recent progress in
      studies of metformin in type 2 diabetes and tumorigenesis, which provides novel
      insight on the therapeutic development of human diseases.

PMID- 30108525
TI  - Borderline Personality Disorder With Cocaine Dependence: Impulsivity, Emotional
      Dysregulation and Amygdala Functional Connectivity.
AB  - Background: Borderline personality disorder is present in 19% of cocaine
      dependence cases; however, this dual pathology is poorly understood. We wished to
      characterize the dual pathology and find its functional connectivity correlates
      to better understand it. Methods: We recruited 69 participants divided into 4
      groups: dual pathology (n = 20), cocaine dependence without borderline
      personality disorder (n = 19), borderline personality without cocaine dependence
      (n = 10) and healthy controls (n = 20). We used self-reported instruments to
      measure impulsivity and emotional dysregulation. We acquired resting state fMRI
      and performed seed-based analyses of the functional connectivity of bilateral
      amygdala. Results: Borderline personality disorder and cocaine dependence as
      factors had opposing effects in impulsivity and emotional dysregulation, as well
      as on functional connectivity between left amygdala and medial prefrontal cortex.
      On the other hand, in the functional connectivity between right amygdala and left
      insula, the effect of having both disorders was instead additive, reducing
      functional connectivity strength. The significant functional connectivity
      clusters were correlated with impulsivity and emotional dysregulation.
      Conclusions: In this study, we found that clinical scores of dual pathology
      patients were closer to those of borderline personality disorder without cocaine
      dependence than to those of cocaine dependence without borderline personality
      disorder, while amygdala-medial prefrontal cortex functional connectivity
      patterns in dual pathology patients were closer to healthy controls than
      expected.

PMID- 30108527
TI  - Prevalence Rates and Predictors of Generalized Anxiety Disorder Symptoms in
      Residents of Fort McMurray Six Months After a Wildfire.
AB  - The Fort McMurray wildfire was the costliest disaster in Canadian history, with
      far-reaching impacts. The purpose of this paper is to examine the prevalence and
      risk factors of elevated generalized anxiety disorder (GAD) symptomatology in
      residents of Fort McMurray 6 months after the wildfire. Data were collected via
      random selection procedures from 486 participants. Generalized anxiety disorder
      symptoms were measured via the GAD-7. The 1-month prevalence rate for GAD
      symptomatology 6 months after the disaster was 19.8% overall, regression analyses
      revealed six variables with significant unique contributions to prediction of GAD
      symptomatology. Significant predictors were: pre-existing anxiety disorder,
      witnessing of homes being destroyed by the wildfire, living in a different home
      after the wildfire, receiving limited governmental support or limited family
      support, and receiving counseling after the wildfire. Participants with these
      risk factors were between two to nearly seven times more likely to present with
      GAD symptomatology. In addition, participants who presented with elevated
      symptomatology were more likely to increase use or problematically use substances
      post-disaster. This study extends the literature on mental health conditions and
      risk factors following disasters, specifically in the area of generalized
      anxiety. Findings and implications are discussed.

PMID- 30108526
TI  - Aberrant Dynamic Functional Network Connectivity and Graph Properties in Major
      Depressive Disorder.
AB  - Major depressive disorder (MDD) is a complex mood disorder characterized by
      persistent and overwhelming depression. Previous studies have identified
      abnormalities in large scale functional brain networks in MDD, yet most of them
      were based on static functional connectivity. In contrast, here we explored
      disrupted topological organization of dynamic functional network connectivity
      (dFNC) in MDD based on graph theory. One hundred and eighty-two MDD patients and
      218 healthy controls were included in this study, all Chinese Han people. By
      applying group information guided independent component analysis (GIG-ICA) to
      resting-state functional magnetic resonance imaging (fMRI) data, the dFNCs of
      each subject were estimated using a sliding window method and k-means clustering.
      Network properties including global efficiency, local efficiency, node strength
      and harmonic centrality, were calculated for each subject. Five dynamic
      functional states were identified, three of which demonstrated significant group
      differences in their percentage of state occurrence. Interestingly, MDD patients
      spent much more time in a weakly-connected State 2, which includes regions
      previously associated with self-focused thinking, a representative feature of
      depression. In addition, the FNCs in MDD were connected differently in different
      states, especially among prefrontal, sensorimotor, and cerebellum networks. MDD
      patients exhibited significantly reduced harmonic centrality primarily involving
      parietal lobule, lingual gyrus and thalamus. Moreover, three dFNCs with disrupted
      node properties were commonly identified in different states, and also correlated
      with depressive symptom severity and cognitive performance. This study is the
      first attempt to investigate the dynamic functional abnormalities in MDD in a
      Chinese population using a relatively large sample size, which provides new
      evidence on aberrant time-varying brain activity and its network disruptions in
      MDD, which might underscore the impaired cognitive functions in this mental
      disorder.

PMID- 30108528
TI  - Differential Noradrenergic Modulation of Monetary Reward and Visual Erotic
      Stimulus Processing.
AB  - We recently investigated the effects of the noradrenergic antidepressant
      reboxetine and the antipsychotic amisulpride compared to placebo on neural
      correlates of primary reinforcers by visual erotic stimulation in healthy
      subjects. Whereas, amisulpride left subjective sexual functions and corresponding
      neural activations unimpaired, attenuated neural activations were observed under
      reboxetine within the nucleus accumbens (Nacc) along with diminished behavioral
      sexual functioning. However, a global dampening of the reward system under
      reboxetine seemed not intuitive considering the complementary role of the
      noradrenergic to the dopamine system in reward-related learning mediated by
      prediction error processing. We therefore investigated the sample of 17 healthy
      males in a mean age of 23.8 years again by functional magnetic resonance imaging
      (fMRI), to explore the noradrenergic effects on neural reward prediction error
      signaling. Participants took reboxetine (4 mg/d), amisulpride (200 mg/d), and
      placebo each for 7 days within a randomized, double-blind, within-subject cross
      over design. During fMRI, we used an established monetary incentive task to
      assess neural reward expectation and prediction error signals within the
      bilateral Nacc using an independent anatomical mask for a region of interest
      (ROI) analysis. Activations within the same ROI were also assessed for the erotic
      picture paradigm. We confirmed our previous results from the whole brain analysis
      for the selected ROI by significant (p < 0.05 FWE-corrected) attenuated
      activations within the Nacc during visual sexual stimulation under reboxetine
      compared to placebo. However, activations in the Nacc concerning prediction error
      processing and monetary reward expectation were unimpaired under reboxetine
      compared to placebo, along with unimpaired reaction times in the reward task. For
      both tasks, neural activations and behavioral processing were not altered by
      amisulpride compared to placebo. The observed attenuated neural activations
      within the Nacc during visual erotic stimulation along with unimpaired neural
      prediction error and monetary reward expectation processing provide evidence for
      a differential modulation of the neural reward system by the noradrenergic agent
      reboxetine depending on the presence of primary reinforcers such as erotic
      stimuli in contrast to secondary such as monetary rewards.

PMID- 30108530
TI  - Psychosocial Predictors of Postpartum Posttraumatic Stress Disorder in Women With
      a Traumatic Childbirth Experience.
AB  - Objective: To analyze the predictive value of antepartum vulnerability factors,
      such as social support, coping, history of psychiatric disease, and fear of
      childbirth, and intrapartum events on the development of symptoms of postpartum
      posttraumatic stress disorder (PP-PTSD) in women with a traumatic childbirth
      experience. Materials and methods: Women with at least one self-reported
      traumatic childbirth experience in or after 2005 were invited to participate
      through various social media platforms in March 2016. They completed a 35-item
      questionnaire including validated screening instruments for PTSD (PTSD Symptom
      Checklist, PCL-5), social support (Oslo social support scale, OSS-3), and coping
      (Antonovsky's sense of coherence scale, SoC). Results: Of the 1,599 women who
      completed the questionnaire, 17.4% met the diagnostic criteria for current PTSD
      according to the DSM-5, and another 26.0% recognized the symptoms from a previous
      period, related to giving birth. Twenty-six percent of the participating women
      had received one or more psychiatric diagnoses at some point in their life, and
      five percent of all women had been diagnosed with PTSD prior to their traumatic
      childbirth experience. Women with poor (OR = 15.320, CI = 8.001-29.336), or
      moderate (OR = 3.208, CI = 1.625-6.333) coping skills were more likely to report
      PP-PTSD symptoms than women with good coping skills. Low social support was
      significantly predictive for current PP-PTSD symptoms compared to high social
      support (OR = 5.557, CI = 2.967-7.785). A predictive model which could
      differentiate between women fulfilling vs. not fulfilling the symptom criteria
      for PTSD had a sensitivity of 80.8% and specificity of 62.6% with an accuracy of
      66.5%. Conclusions: Low social support, poor coping, experiencing "threatened
      death" and experiencing "actual or threatened injury to the baby" were the four
      significant factors in the predictive model for women with a traumatic childbirth
      experience to be at risk of developing PP-PTSD. Further research should
      investigate the effects of interventions aimed at the prevention of PP-PTSD by
      strengthening coping skills and increasing social support, especially in women at
      increased risk of unfavorable obstetrical outcomes.

PMID- 30108529
TI  - Auditory Verbal Hallucinations in Borderline Personality Disorder and the
      Efficacy of Antipsychotics: A Systematic Review.
AB  - Background: Auditory verbal hallucinations (AVH) are experienced more frequently
      by patients with borderline personality disorder (BPD) than previously assumed.
      However, consensus is lacking on how to treat them. Objective: To provide a
      systematic review of studies reporting on AVH in patients with BPD, with a focus
      on the efficacy of treatment of psychotic symptoms. Methods: For this review a
      systematic search was made in the PubMed and Ovid databases, and mean weighted
      prevalence rates, adjusted for sample size, were computed. Results: The search
      yielded 36 studies describing a total of 1,263 patients. Auditory hallucinations
      (including AVH) were reported in 27% of hospitalized BPD patients; AVH were
      reported in 25% of all patients and in 24% of outpatients. Of the hallucinating
      patients, 78% experienced AVH at least once per day, for a duration of several
      days to many years. On the whole, patients with BPD regarded their voices as
      malevolent and omnipotent in nature. Compared to patients with schizophrenia, the
      phenomenological characteristics of AVH were similar and the ensuing distress was
      equal or even higher, whereas scores for other positive symptoms were lower. The
      presence of AVH in BPD was associated with an increase of suicide plans and
      attempts, and more frequent hospitalization. Moreover, AVH in the context of BPD
      were associated with higher prevalence rates for post-traumatic stress disorder
      and emotional abuse. The efficacy of antipsychotics was investigated in 21
      studies. Based on these studies, we conclude that both typical and atypical
      antipsychotics tend to have positive effects on AVH experienced in the context of
      BPD. The efficacy of cognitive-behavioral therapy and non-invasive brain
      stimulation has not yet been systematically assessed. Conclusions: These findings
      indicate that AVH experienced in the context of BPD are in need of proper
      diagnosis and treatment, and that antipsychotics tend to be beneficial in
      treating these (and other psychotic) symptoms.There is an urgent need for studies
      assessing the efficacy of cognitive-behavioral therapy and non-invasive brain
      stimulation in this underdiagnosed and undertreated group.

PMID- 30108531
TI  - Email Overload? Brain and Behavioral Responses to Common Messaging Alerts Are
      Heightened for Email Alerts and Are Associated With Job Involvement.
AB  - We tested brain and behavioral responses to two common messaging alerts (Outlook
      and Android whistle) using an oddball paradigm, where participants had to detect
      the two alerts among a background of white noise and occasional matched,
      distractor stimuli. Twenty-nine participants were tested using a behavioral
      target detection task and a subset of 14 were tested both with event-related
      potential (ERP) and behavioral oddball detection. For the ERP recordings,
      participants were instructed to attend to a distractor DVD in one condition and
      in the other, to actively attend to the stimuli. We measured mismatch negativity
      (MMN) and P3a components and questionnaire responses to job involvement,
      rumination and work-life balance. There were significantly larger MMN responses
      to target alert signals, but only in the ignore condition. In both ignore and
      attend conditions, MMN was larger for the Android stimuli, probably as a result
      of the larger physical discriminability for the Android tone. On the other hand,
      there was a significant P3a for Outlook tones, but not for Android tones in the
      ignore condition. Neither alert showed significant P3a activity within the attend
      condition, but instead later frontal positivity, which was larger for the Outlook
      alert (in comparison to its matched distractor) and this effect was not seen for
      the Android tones. This was despite the Outlook alert being less perceptually
      discriminable compared to the Android alert. These findings suggest that the
      indices of attentional processing are more affected by the significance of the
      alert than the physical qualities. These effects were coupled with the finding
      that the faster reaction times to the Outlook sounds were correlated with greater
      job involvement. These data suggest that work-related messages might signal
      greater attentional switch and effort which in turn may feed into greater job
      involvement.

PMID- 30108532
TI  - Creating Images With the Stroke of a Hand: Depiction of Size and Shape in Sign
      Language.
AB  - In everyday communication, not only do speakers describe, but they also depict.
      When depicting, speakers take on the role of other people and quote their speech
      or imitate their actions. In previous work, we developed a paradigm to elicit
      depictions in speakers. Here we apply this paradigm to signers to explore
      depiction in the manual modality, with a focus on depiction of the size and shape
      of objects. We asked signers to describe two objects that could easily be
      characterized using lexical signs (Descriptive Elicitation), and objects that
      were more difficult to distinguish using lexical signs, thus encouraging the
      signers to depict (Depictive Elicitation). We found that signers used two types
      of depicting constructions (DCs), conventional DCs and embellished DCs. Both
      conventional and embellished DCs make use of categorical handshapes to identify
      objects. But embellished DCs also capture imagistic aspects of the objects,
      either by adding a tracing movement to gradiently depict the contours of the
      object, or by adding a second handshape to depict the configuration of the
      object. Embellished DCs were more frequent in the Depictive Elicitation context
      than in the Descriptive Elicitation context; lexical signs showed the reverse
      pattern; and conventional DCs were equally like in the two contexts. In addition,
      signers produced iconic mouth movements, which are temporally and semantically
      integrated with the signs they accompany and depict the size and shape of
      objects, more often with embellished DCs than with either lexical signs or
      conventional DCs. Embellished DCs share a number of properties with embedded
      depictions, constructed action, and constructed dialog in signed and spoken
      languages. We discuss linguistic constraints on these gradient depictions,
      focusing on how handshape constrains the type of depictions that can be formed,
      and the function of depiction in everyday discourse.

PMID- 30108534
TI  - Linking Empowering Leadership and Employee Work Engagement: The Effects of Person
      Job Fit, Person-Group Fit, and Proactive Personality.
AB  - Based on person-environment fit theory, this study examined the effects of
      empowering leadership on employee work engagement. We also investigated the
      mediating mechanism of person-job fit and person-group fit. In addition, we
      explored employee proactive personality's moderating role between empowering
      leadership and the above two kinds of fit, and then the set of indirect effects.
      Using a survey sample of 6179 employees from a technology company in China, we
      found that empowering leadership has a positively indirect influence on employees
      work engagement though person-job fit and person-group fit. Further, moderated
      mediation analysis revealed proactive personality augmented empowering leadership
      direct effect on person-job fit and person-group fit and indirect effect on work
      engagement. Theoretical and practical implications were also discussed.

PMID- 30108533
TI  - Is Parent-Child Disagreement on Child Anxiety Explained by Differences in
      Measurement Properties? An Examination of Measurement Invariance Across
      Informants and Time.
AB  - There are numerous empirical studies demonstrating that agreement between parent
      reports of youth and youth self-reports of internalizing behavior problems is
      modest at best. This has spurred much research on factors that influence the
      magnitude of associations between informants, including individual difference
      characteristics of the informants and contexts through which individuals interact
      with the child. There is also tremendous interest in understanding symptom
      trajectories longitudinally. However, each of these lines of work are predicated
      on the assumptions that the psychometric construct that is being assessed from
      each informant and at each measurement occasion is the same. This study examined
      measurement invariance between maternal and child reports and longitudinally
      across ages 9 and 12 on five dimensions of anxiety using the Screen for Child
      Anxiety and Related Disorders (SCARED; Birmaher et al., 1999). No cross-informant
      models for anxiety dimensions achieved acceptable fit and at least partial metric
      and scalar invariance. Moreover, few longitudinal models demonstrated acceptable
      fit and at least partial metric and scalar invariance. Thus, using the SCARED as
      an example, these results show that inter-informant agreement may be compromised
      by different item functioning, and highlight the need for testing invariance
      before using measures for longitudinal tracking of symptoms.

PMID- 30108536
TI  - Who Is the Rightful Owner? Young Children's Ownership Judgments in Different
      Transfer Contexts.
AB  - This study aimed to examine whether Chinese preschoolers understand that
      ownership can be transferred in different contexts. The study participants were 3
      to 5-year-old Chinese children (n = 96) and adults (n = 34). With four scenarios
      that contained different transfer types (giving, stealing, losing, and
      abandoning), participants were asked four questions about ownership. The results
      indicated that preschoolers' ability to distinguish legitimate ownership
      transfers from illegitimate ownership transfers improved with age. Three-year
      olds understood that ownership cannot be transferred in a stealing context, but
      the appropriate understanding of ownership was not attained until 4 years old in
      a giving context and 5 years old in losing and abandoning contexts, which is
      similar to the adults' performance. In addition to the first possessor bias (a
      tendency to judge the first possessor as the owner) found in previous studies, 3
      year-olds also displayed a loan bias (a tendency to believe everything that is
      transferred should be returned) in the study. The findings suggest that the
      developmental trajectories of preschoolers' understanding of ownership transfers
      varied across different contexts, which may relate to children's ability to
      consider the role of intent in determining ownership and parents' disciplinary
      behavior. Both cross-cultural similarities and differences are discussed.

PMID- 30108535
TI  - Does Holistic Processing Require a Large Brain? Insights From Honeybees and Wasps
      in Fine Visual Recognition Tasks.
AB  - The expertise of humans for recognizing faces is largely based on holistic
      processing mechanism, a sophisticated cognitive process that develops with visual
      experience. The various visual features of a face are thus glued together and
      treated by the brain as a unique stimulus, facilitating robust recognition.
      Holistic processing is known to facilitate fine discrimination of highly similar
      visual stimuli, and involves specialized brain areas in humans and other
      primates. Although holistic processing is most typically employed with face
      stimuli, subjects can also learn to apply similar image analysis mechanisms when
      gaining expertise in discriminating novel visual objects, like becoming experts
      in recognizing birds or cars. Here, we ask if holistic processing with expertise
      might be a mechanism employed by the comparatively miniature brains of insects.
      We thus test whether honeybees (Apis mellifera) and/or wasps (Vespula vulgaris)
      can use holistic-like processing with experience to recognize images of human
      faces, or Navon-like parameterized-stimuli. These insect species are excellent
      visual learners and have previously shown ability to discriminate human face
      stimuli using configural type processing. Freely flying bees and wasps were
      consequently confronted with classical tests for holistic processing, the part
      whole effect and the composite-face effect. Both species could learn similar
      faces from a standard face recognition test used for humans, and their
      performance in transfer tests was consistent with holistic processing as defined
      for studies on humans. Tests with parameterized stimuli also revealed a capacity
      of honeybees, but not wasps, to process complex visual information in a holistic
      way, suggesting that such sophisticated visual processing may be far more spread
      within the animal kingdom than previously thought, although may depend on
      ecological constraints.

PMID- 30108537
TI  - Eye-Closure Enhances Creative Performance on Divergent and Convergent Creativity
      Tasks.
AB  - In today's world of rapid changes and increasing complexity, understanding and
      enhancing creativity is of critical importance. Studies investigating EEG
      correlates of creativity linked power in the alpha frequency band to creativity,
      and alpha-power has been interpreted as reflecting attention on internal mental
      representations and inhibition of external sensory input. Thus far, however,
      there is no direct evidence for the idea that internally directed attention
      facilitates creativity. The aim of the current study was to experimentally
      investigate the relationship between eye-closure-a simple and effective means to
      stimulate internally directed attention-and creativity. Moreover, to test whether
      the potential beneficial effect of eye-closure is specific for creativity, or
      whether it improves general cognitive functioning, the current study tested the
      effect of eye-closure on creativity and on working memory (WM). Participants
      completed four tasks to measure divergent and convergent creativity (Adapted
      Alternative Uses (AAU) Test, Remote Associates Test (RAT), Sentence Construction
      Test, and Word Construction Test), and one task to measure WM (Digit Span Test).
      For each task, participants had to perform two versions, one version with eyes
      open and one version with eyes closed. Eye-closure facilitated creative
      performance on the classical divergent and convergent creativity tasks (AAU Test
      and RAT). No effect of eye-closure was observed on the WM task. These findings
      provide a novel and easily applicable means to enhance divergent and convergent
      creativity through eye-closure.

PMID- 30108540
TI  - Linking Transformational Leadership and Knowledge Sharing: The Mediating Roles of
      Perceived Team Goal Commitment and Perceived Team Identification.
AB  - It is widely assumed that transformational leadership can effectively facilitate
      the sharing of knowledge among followers, but most investigations of the
      underlying mechanisms were based on the social exchange perspective. Based on a
      sensegiving theory perspective, this article attempts to uncover the mechanisms
      by which transformational leadership has its impact on employee knowledge sharing
      behavior by proposing two team-directed mediating mechanisms: perceived team goal
      commitment and perceived team identification. Results of multi-source and time
      lagged data from 186 leader-follower pairs supported the proposed mediating
      effects. Implications and limitations are discussed.

PMID- 30108538
TI  - No Differential Effects of Neural and Psychological Explanations of Psychopathy
      on Moral Behavior.
AB  - Research in neurocriminology has explored the link between neural functions and
      structures and the psychopathic disposition. This online experiment aimed to
      assess the effect of communicating the neuroscience of psychopathy on the degree
      to which lay people exhibited attitudes characteristic of psychopathy in
      particular in terms of moral behavior. If psychopathy is blamed on the brain,
      people may feel less morally responsible for their own psychopathic tendencies.
      In the study, participants read false feedback about their own psychopathic
      traits supposedly inferred from their Facebook likes, described either in
      neurobiological or cognitive terms. Participants were randomly allocated to read
      that they either had above-average or below-average psychopathic traits. We found
      no support for the hypothesis that the neuroscientific explanation of psychopathy
      influences moral behavior. This casts doubt on the fear that communicating the
      neuroscience of psychopathy will promote psychopathic attitudes.

PMID- 30108539
TI  - Maternal Odor Exposure Modulates Acceptance of a Bitter Taste in Newborn and
      Infant Rats.
AB  - The acceptance of bitter, aversive, substances during early life is enhanced by
      stimulation with familiar, pre-exposed odors. Newborn rats exhibited heightened
      grasp responses toward an artificial nipple dispensing quinine, and drank more of
      this bitter solution, if concurrently stimulated with a lemon odor they had been
      exposed to shortly after birth. It yet unknown, however, if odors made familiar
      via normative developmental milestones also acquire modulatory influence upon
      seeking and intake of basic tastants. The current study assessed the influence of
      exposure to maternal odor on intake and grasp responses toward a surrogate nipple
      providing quinine, in 3-day (Experiment 1) or 12-day (Experiment 2) old, Wistar
      rat pups. The results revealed enhanced seeking and intake of the bitter
      solution, but not of water, in animals tested in the presence of the mother (and
      hence exposed to its odor cues), at both ages, compared to counterparts given
      either no explicit odor stimulation or stimulation to the odor of an unrelated
      dam. These results, obtained with a biologically relevant odor, are consistent
      with those previously found with a neutral, arbitrary odor. It seems that during
      the early stages of development, familiar odors regulate the acceptance of non
      palatable, otherwise rejected, flavors.

PMID- 30108541
TI  - Relationship Between Theory of Mind, Emotion Recognition, and Social Synchrony in
      Adolescents With and Without Autism.
AB  - Difficulty in social communication and interaction is a primary diagnostic
      feature of ASD. Research has found that adolescents with ASD display various
      impairments in social behavior such as theory of mind (ToM), emotion recognition,
      and social synchrony. However, not much is known about the relationships among
      these dimensions of social behavior. Adolescents with and without ASD
      participated in the study. ToM ability was measured by viewing social animations
      of geometric shapes, recognition of facial emotions was measured by viewing
      pictures of faces, and synchrony ability was measured with a spontaneously
      arising interpersonal movement task completed with a caregiver and an intentional
      interpersonal task. Attention and social responsiveness were measured using
      parent reports. We then examined the relationship between ToM, emotion
      recognition, clinical measures of attention and social responsiveness, and social
      synchronization that arises either spontaneously or intentionally. Results
      indicate that spontaneous synchrony was related to ToM and intentional synchrony
      was related to clinical measures of attention and social responsiveness. Facial
      emotion recognition was not related to either ToM or social synchrony. Our
      findings highlight the importance of biological motion perception and production
      and attention for more fully understanding the social behavior characteristic of
      ASD. The findings suggest that the processes underlying difficulties in
      spontaneous synchrony in ASD are different than the processes underlying
      difficulties in intentional synchronization.

PMID- 30108542
TI  - Mathematically Gifted Accelerated Students Participating in an Ability Group: A
      Qualitative Interview Study.
AB  - Schools in Norway often emphasize heterogeneous groups in education. The
      postulated negative effects of homogeneous ability groups on motivation and
      academic self-concept have long been debated. This study uses semi-structured
      interviews to investigate how a group of 11 accelerated and ability-grouped high
      ability students (gifted) in math have experienced school. All students were
      interviewed individually. This study explores categories connected to the
      students' motivation for the subject, challenges in school, peer and teacher
      relationships, and academic self-concept. The aim of the study is to investigate
      whether the school system is able to provide an adequate learning environment for
      high-ability students, both in ordinary class and in ability groups. The findings
      show that although some of the needs of high-ability students in Norway are being
      met, there is much work to be done before an optimal learning environment is
      established for these students. For example, students do not receive sufficient
      challenges in math. Furthermore, teachers in the early years of school lack
      sufficient mathematical knowledge to challenge and support mathematically gifted
      students, students' motivation for the subject is lower than expected, and boys'
      self-concept seems to be higher than that of girls.

PMID- 30108545
TI  - Novel TBC1D24 Mutations in a Case of Nonconvulsive Status Epilepticus.
AB  - Objective: Nonconvulsive status epilepticus (NCSE) is an uncommon clinical
      manifestation in patients with TBC1D24 mutations. In addition, NCSE has not been
      reported as a syndrome together with cerebellar ataxia and ophthalmoplegia.
      Methods: We herein report the clinical and genetic features of a four-year-old
      patient with NCSE, cerebellar ataxia, and ophthalmoplegia caused by hitherto
      unidentified TBC1D24 mutations. We performed 24-h video electroencephalogram
      (EEG), magnetic resonance imaging, and gene sequencing on the patient and her
      parents to determine the diagnosis. Results: We identified a novel c.1416_1437del
      (p.Ser473Argfs*43) mutation, as well as the previously identified c.1499C>T
      (p.Ala500Val) mutation in TBC1D24, by using targeted next-generation sequencing.
      The novel mutation (inherited from the mother) is the first reported deletion
      mutation longer than 20 bp in TBC1D24. The p.Ala500Val mutation inherited from
      father has been reported in a German patient with infantile myoclonic, for whom
      results from the EEG and neuroimaging were normal. These two mutations resulted
      in the severe phenotypes observed in our patient Conclusions: The identification
      of the novel TBC1D24 mutation and consequent complicated clinical manifestations
      suggest that patients with NCSE and ataxia demand more attention. We further
      recommend that genetic test should be administered to these patients to avoid
      genetic inheritance of this mutation.

PMID- 30108544
TI  - Neuroprotective Effect of Artesunate in Experimental Model of Traumatic Brain
      Injury.
AB  - Traumatic brain injuries (TBI) are an important public health challenge. In
      addition, subsequent events at TBI can compromise the quality of life of these
      patients. In fact, TBI is associated with several complications for both long and
      short term, some evidence shows how TBI is associated with a decline in cognitive
      functions such as the risk of developing dementia, cerebral atrophy, and
      Parkinson disease. After the direct damage from TBI, a key role in TBI injury is
      played by the inflammatory response and oxidative stress, that contributes to
      tissue damage and to neurodegenerative processes, typical of secondary injury,
      after TBI. Given the complex series of events that are involved after TBI injury,
      a multitarget pharmacological approach is needed. Artesunate is a more stable
      derivative of its precursor artemisin, a sesquiterpene lactone obtained from a
      Chinese plant Artemisia annua, a plant used for centuries in traditional Chinese
      medicine. artesunate has been shown to be a pluripotent agent with different
      pharmacological actions. therefore, in this experimental model of TBI we
      evaluated whether the treatment with artesunate at the dose of 30 mg?Kg, had an
      efficacy in reducing the neuroinflammatory process after TBI injury, and in
      inhibiting the NLRP3 inflammasome pathway, which plays a key role in the
      inflammatory process. We also assessed whether treatment with artesunate was able
      to exert a neuroprotective action by modulating the release of neurotrophic
      factors. our results show that artesunate was able to reduce the TBI-induced
      lesion, it also showed an anti-inflammatory action through the inhibition of Nf
      kb, release of proinflammatory cytokines IL-1beta and TNF-alpha and through the
      inhibition NLRP3 inflammasome complex, furthermore was able to reduce the
      activation of astrocytes and microglia (GFAP, Iba-1). Finally, our results show
      that the protective effects of artesunate also occur through the modulation of
      neurotrophic factors (BDNF, GDNF, NT-3) that play a key role in neuronal
      survival.

PMID- 30108543
TI  - Deep Brain Stimulation in Moroccan Patients With Parkinson's Disease: The
      Experience of Neurology Department of Rabat.
AB  - Introduction: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is
      known as a therapy of choice of advanced Parkinson's disease. The present study
      aimed to assess the beneficial and side effects of STN DBS in Moroccan
      Parkinsonian patients. Material and Methods: Thirty five patients underwent
      bilateral STN DBS from 2008 to 2016 in the Rabat University Hospital. Patients
      were assessed preoperatively and followed up for 6 to 12 months using the Unified
      Parkinson's Disease Rating Scale in four conditions (stimulation OFF and ON and
      medication OFF and ON), the levodopa-equivalent daily dose (LEDD), dyskinesia and
      fluctuation scores and PDQ39 scale for quality of life (QOL). Postoperative side
      effects were also recorded. Results: The mean age at disease onset was 42.31 +/-
      7.29 years [28-58] and the mean age at surgery was 54.66 +/- 8.51 years [34-70].
      The median disease duration was 11.95 +/- 4.28 years [5-22]. Sixty-three
      percentage of patients were male. 11.4% of patients were tremor dominant while
      45.71 showed akinetic-rigid form and 42.90 were classified as mixed phenotype.
      The LEDD before surgery was 1200 mg/day [800-1500]. All patients had motor
      fluctuations whereas non-motor fluctuations were present in 61.80% of cases. STN
      DBS decreased the LEDD by 51.72%, as the mean LEDD post-surgery was 450 [188
      800]. The UPDRS-III was improved by 52.27%, dyskinesia score by 66.70% and motor
      fluctuations by 50%, whereas QOL improved by 27.12%. Post-operative side effects
      were hypophonia (2 cases), infection (3 cases), and pneumocephalus (2 cases).
      Conclusion: Our results showed that STN DBS is an effective treatment in Moroccan
      Parkinsonian patients leading to a major improvement of the most disabling
      symptoms (dyskinesia, motor fluctuation) and a better QOL.

PMID- 30108546
TI  - Contribution of Neurochemical Inputs to the Decrease of Motoneuron Excitability
      During Non-REM and REM Sleep: A Systematic Review.
AB  - The sleep-related depression of excitability of upper airway motoneurons is a
      major neurological cause of obstructive sleep apnea whereas a disruption in the
      inhibition of spinal motoneurons during rapid eye movement (REM) sleep causes the
      REM sleep behavioral disorder. The large amount of experimental data has been
      obtained that deal with neurochemical mechanisms that are responsible for sleep
      related depression of various motoneuron groups. However, there is a disagreement
      regarding the outcome of these studies primarily due to the use of different
      animal models and approaches, as well as due to differences in quantification and
      interpretation of obtained results. In this study, we sought to apply the same
      calculation methodology in order to uniformly quantify and compare the relative
      contribution of excitatory or inhibitory inputs to the decrease of excitability
      of different motoneuronal pools during REM and/or non-REM sleep. We analyzed only
      published quantitative data that were obtained by using receptor antagonists or
      chemogenetic approach to block receptors or silence neuronal populations. The
      outcomes of this analysis highlight the differences in the neurotransmitter
      mechanisms of sleep-related motoneuron depression between different motoneuronal
      pools and demonstrate the consistency of these mechanisms for hypoglossal
      motoneurons among various animal models.

PMID- 30108549
TI  - Depression and Obesity: Integrating the Role of Stress, Neuroendocrine
      Dysfunction and Inflammatory Pathways.
AB  - Literature on depression and obesity describes the relevance of the hypothalamic
      pituitary adrenal axis dysfunction, sympathetic nervous system (SNS) activation,
      and inflammatory processes as well as the interaction of genetic and
      environmental factors. Recent investigation in obesity highlights the involvement
      of several regulation systems, particularly in white adipose tissue. The
      hypothalamic pituitary adrenal axis, gonadal, growth hormone, leptin, sympathetic
      nervous system and adrenergic, dopaminergic, and serotoninergic central pathways,
      all seem interconnected and involved in obesity. From another perspective, the
      role of psychosocial chronic stressors, determining poor mental and physical
      health, is well documented. Empirical data can support biologically conceivable
      theories describing how perceptions of the external social environment are
      transduced into cellular inflammation and depression. Although in neurobiological
      models of depression, stress responses are associated with neuroendocrine and
      neuro-inflammatory processes, concerning similar pathways to those described in
      obesity, an integrating model is still lacking. The aim of this mini-review is to
      offer a reflexion on the interplay between the neuroendocrine dysfunctions
      related to chronic stress and the nature of the shared biologic mechanisms in the
      pathophysiology of both clinical entities, depression and obesity. We highlight
      dysfunctional answers of mind body systems that are usually activated to promote
      regulation and adaptation. Stress response, as a mediator between different level
      phenomena, may undertake the role of a plausible link between psychological and
      biological determinants of disease. Depression and obesity are major public
      health issues, urging for new insights and novel interventions and this
      discussion points to the need of a more in-depth approach.

PMID- 30108550
TI  - Combinational Inhibitory Action of Hedychium spicatum L. Essential Oil and gamma
      Radiation on Growth Rate and Mycotoxins Content of Fusarium graminearum in Maize:
      Response Surface Methodology.
AB  - Nowadays, contamination of agricultural commodities with fungi and their
      mycotoxins is one of the most annoying with regard to food safety and pose
      serious health risk. Therefore, there is a requisite to propose suitable
      mitigation strategies to reduce the contamination of fungi and mycotoxins in
      agricultural commodities. In the present study, combinational inhibitory effect
      of Hedychium spicatum L. essential oil (HSEO) and radiation was established on
      growth rate, production of deoxynivalenol (DON) and zearalenone (ZEA) by Fusarium
      graminearum in maize grains. The HSEO was obtained from rhizomes by
      hydrodistillation technique and chemical composition was revealed by GC-MS
      analysis. A total of 48 compounds were identified and major compounds were 1,8
      cineole (23.15%), linalool (12.82%), and beta-pinene (10.06%). The discrete
      treatments of HSEO and radiation were effective in reducing the fungal growth
      rate and mycotoxins content, and the complete reduction was noticed at 3.15 mg/g
      of HSEO and 6 kGy of radiation. Response surface methodology (RSM) was applied to
      evaluate the combinational inhibitory effect of HSEO and radiation treatments on
      fungal growth rate and mycotoxins content. A total of 13 experiments were
      designed with distinct doses of HSEO and radiation by central composite design
      (CCD) of Stat-Ease Design-Expert software. In combinational approach, complete
      reductions of fungal growth, DON, and ZEA content were noticed at 1.89 mg/g of
      HSEO and 4.12 kGy of radiation treatments. The optimized design concluded that
      combinational treatments of HSEO and radiation were much more effective in
      reducing the fungal growth and mycotoxins content compared to their discrete
      treatments (p < 0.05). Responses of the design were assessed by second-order
      polynomial regression analysis and found that quadratic model was well fitted.
      The optimized design has larger F-value and adequate precision, smaller p-value,
      decent regression coefficients (R2 ) and found statistically significant (p <
      0.05). In addition, correlation matrix, normal plot residuals, Box-Cox, and
      actual vs. predicted plots were endorsed that optimized design was accurate and
      appropriate. The proposed combinational decontamination technique could be highly
      applicable in agriculture and food industry to safeguard the food and feed
      products from fungi and mycotoxins.

PMID- 30108551
TI  - Comparative Transcriptomics of Cold Growth and Adaptive Features of a Eury- and
      Steno-Psychrophile.
AB  - Permafrost subzero environments harbor diverse, active communities of
      microorganisms. However, our understanding of the subzero growth, metabolisms,
      and adaptive properties of these microbes remains very limited. We performed
      transcriptomic analyses on two subzero-growing permafrost isolates with different
      growth profiles in order to characterize and compare their cold temperature
      growth and cold-adaptive strategies. The two organisms, Rhodococcus sp. JG3 (-5
      to 30 degrees C) and Polaromonas sp. Eur3 1.2.1 (-5 to 22 degrees C), shared
      several common responses during low temperature growth, including induction of
      translation and ribosomal processes, upregulation of nutrient transport,
      increased oxidative and osmotic stress responses, and stimulation of
      polysaccharide capsule synthesis. Recombination appeared to be an important
      adaptive strategy for both isolates at low temperatures, likely as a mechanism to
      increase genetic diversity and the potential for survival in cold systems. While
      Rhodococcus sp. JG3 favored upregulating iron and amino acid transport,
      sustaining redox potential, and modulating fatty acid synthesis and composition
      during growth at -5 degrees C compared to 25 degrees C, Polaromonas sp. Eur3
      1.2.1 increased the relative abundance of transcripts involved in primary energy
      metabolism and the electron transport chain, in addition to signal transduction
      and peptidoglycan synthesis at 0 degrees C compared to 20 degrees C. The increase
      in energy metabolism may explain why Polaromonas sp. Eur3 1.2.1 is able to
      sustain growth rates at 0 degrees C comparable to those at higher temperatures.
      For Rhodococcus sp. JG3, flexibility in use of carbon sources, iron acquisition,
      control of membrane fatty acid composition, and modulating redox and co-factor
      potential may be ways in which this organism is able to sustain growth over a
      wider range of temperatures. Increasing our understanding of the microbes in
      these habitats helps us better understand active pathways and metabolisms in
      extreme environments. Identifying novel, thermolabile, and cold-active enzymes
      from studies such as this is also of great interest to the biotechnology and food
      industries.

PMID- 30108552
TI  - Microscale Heterogeneity of the Spatial Distribution of Organic Matter Can
      Promote Bacterial Biodiversity in Soils: Insights From Computer Simulations.
AB  - There is still no satisfactory understanding of the factors that enable soil
      microbial populations to be as highly biodiverse as they are. The present article
      explores in silico the hypothesis that the heterogeneous distribution of soil
      organic matter, in addition to the spatial connectivity of the soil moisture,
      might account for the observed microbial biodiversity in soils. A multi-species,
      individual-based, pore-scale model is developed and parameterized with data from
      3 Arthrobacter sp. strains, known to be, respectively, competitive, versatile,
      and poorly competitive. In the simulations, bacteria of each strain are
      distributed in a 3D computed tomography (CT) image of a real soil and three water
      saturation levels (100, 50, and 25%) and spatial heterogeneity levels (high,
      intermediate, and low) in the distribution of the soil organic matter are
      considered. High and intermediate heterogeneity levels assume, respectively, an
      amount of particulate organic matter (POM) distributed in a single (high
      heterogeneity) or in four (intermediate heterogeneity) randomly placed fragments.
      POM is hydrolyzed at a constant rate following a first-order kinetic, and
      continuously delivers dissolved organic carbon (DOC) into the liquid phase, where
      it is then taken up by bacteria. The low heterogeneity level assumes that the
      food source is available from the start as DOC. Unlike the relative abundances of
      the 3 strains, the total bacterial biomass and respiration are similar under the
      high and intermediate resource heterogeneity schemes. The key result of the
      simulations is that spatial heterogeneity in the distribution of organic matter
      influences the maintenance of bacterial biodiversity. The least competing strain,
      which does not reach noticeable growth for the low and intermediate spatial
      heterogeneities of resource distribution, can grow appreciably and even become
      more abundant than the other strains in the absence of direct competition, if the
      placement of the resource is favorable. For geodesic distances exceeding 5 mm,
      microbial colonies cannot grow. These conclusions are conditioned by assumptions
      made in the model, yet they suggest that microscale factors need to be considered
      to better understand the root causes of the high biodiversity of soils.

PMID- 30108548
TI  - Involvement of TRPV1 Channels in Energy Homeostasis.
AB  - The ion channel TRPV1 is involved in a wide range of processes including
      nociception, thermosensation and, more recently discovered, energy homeostasis.
      Tightly controlling energy homeostasis is important to maintain a healthy body
      weight, or to aid in weight loss by expending more energy than energy intake.
      TRPV1 may be involved in energy homeostasis, both in the control of food intake
      and energy expenditure. In the periphery, it is possible that TRPV1 can impact on
      appetite through control of appetite hormone levels or via modulation of
      gastrointestinal vagal afferent signaling. Further, TRPV1 may increase energy
      expenditure via heat production. Dietary supplementation with TRPV1 agonists,
      such as capsaicin, has yielded conflicting results with some studies indicating a
      reduction in food intake and increase in energy expenditure, and other studies
      indicating the converse. Nonetheless, it is increasingly apparent that TRPV1 may
      be dysregulated in obesity and contributing to the development of this disease.
      The mechanisms behind this dysregulation are currently unknown but interactions
      with other systems, such as the endocannabinoid systems, could be altered and
      therefore play a role in this dysregulation. Further, TRPV1 channels appear to be
      involved in pancreatic insulin secretion. Therefore, given its plausible
      involvement in regulation of energy and glucose homeostasis and its dysregulation
      in obesity, TRPV1 may be a target for weight loss therapy and diabetes. However,
      further research is required too fully elucidate TRPV1s role in these processes.
      The review provides an overview of current knowledge in this field and potential
      areas for development.

PMID- 30108547
TI  - Biomarkers for Macrosomia Prediction in Pregnancies Affected by Diabetes.
AB  - Large birthweight, or macrosomia, is one of the commonest complications for
      pregnancies affected by diabetes. As macrosomia is associated with an increased
      risk of a number of adverse outcomes for both the mother and offspring, accurate
      antenatal prediction of fetal macrosomia could be beneficial in guiding
      appropriate models of care and interventions that may avoid or reduce these
      associated risks. However, current prediction strategies which include physical
      examination and ultrasound assessment, are imprecise. Biomarkers are proving
      useful in various specialties and may offer a new avenue for improved prediction
      of macrosomia. Prime biomarker candidates in pregnancies with diabetes include
      maternal glycaemic markers (glucose, 1,5-anhydroglucitol, glycosylated
      hemoglobin) and hormones proposed implicated in placental nutrient transfer
      (adiponectin and insulin-like growth factor-1). There is some support for an
      association of these biomarkers with birthweight and/or macrosomia, although
      current evidence in this emerging field is still limited. Thus, although
      biomarkers hold promise, further investigation is needed to elucidate the
      potential clinical utility of biomarkers for macrosomia prediction for
      pregnancies affected by diabetes.

PMID- 30108554
TI  - Enhancing Production of Pinene in Escherichia coli by Using a Combination of
      Tolerance, Evolution, and Modular Co-culture Engineering.
AB  - alpha-Pinene is a natural and active monoterpene, which is widely used as a
      flavoring agent and in fragrances, pharmaceuticals, and biofuels. Although it has
      been successfully produced by genetically engineered microorganisms, the
      production level of pinene is much lower than that of hemiterpene (isoprene) and
      sesquiterpenes (farnesene) to date. We first improved pinene tolerance to 2.0%
      and pinene production by adaptive laboratory evolution after atmospheric and room
      temperature plasma (ARTP) mutagenesis and overexpression of the efflux pump to
      obtain the pinene tolerant strain Escherichia coli YZFP, which is resistant to
      fosmidomycin. Through error-prone PCR and DNA shuffling, we isolated an Abies
      grandis geranyl pyrophosphate synthase variant that outperformed the wild-type
      enzyme. To balance the expression of multiple genes, a tunable intergenic region
      (TIGR) was inserted between A. grandis GPPSD90G/L175P and Pinus taeda Pt1Q457L .
      In an effort to improve the production, an E. coli-E. coli modular co-culture
      system was engineered to modularize the heterologous mevalonate (MEV) pathway and
      the TIGR-mediated gene cluster of A. grandis GPPSD90G/L175P and P. taeda Pt1Q457L
      . Specifically, the MEV pathway and the TIGR-mediated gene cluster were
      integrated into the chromosome of the pinene tolerance strain E. coli YZFP and
      then evolved to a higher gene copy number by chemically induced chromosomal
      evolution, respectively. The best E. coli-E. coli co-culture system of
      fermentation was found to improve pinene production by 1.9-fold compared to the
      mono-culture approach. The E. coli-E. coli modular co-culture system of whole
      cell biocatalysis further improved pinene production to 166.5 mg/L.

PMID- 30108553
TI  - Soil Microbial Resources for Improving Fertilizers Efficiency in an Integrated
      Plant Nutrient Management System.
AB  - Tomorrow's agriculture, challenged by increasing global demand for food, scarcity
      of arable lands, and resources alongside multiple environment pressures, needs to
      be managed smartly through sustainable and eco-efficient approaches. Modern
      agriculture has to be more productive, sustainable, and environmentally friendly.
      While macronutrients such as nitrogen (N), phosphorus (P), potassium (K), and
      sulfur (S) supplied by mineral fertilizers are vital to crop production,
      agriculturally beneficial microorganisms may also contribute directly (i.e.,
      biological N2 fixation, P solubilization, and phytohormone production, etc.) or
      indirectly (i.e., antimicrobial compounds biosynthesis and elicitation of induced
      systemic resistance, etc.) to crop improvement and fertilizers efficiency.
      Microbial-based bioformulations that increase plant performance are greatly
      needed, and in particular bioformulations that exhibit complementary and
      synergistic effects with mineral fertilization. Such an integrated soil fertility
      management strategy has been demonstrated through several controlled and non
      controlled experiments, but more efforts have to be made in order to thoroughly
      understand the multiple functions of beneficial microorganisms within the soil
      microbial community itself and in interaction with plants and mineral resources.
      In fact, the combined usage of microbial [i.e., beneficial microorganisms: N2
      fixing (NF), P-solubilizing, and P mobilizing, etc.] and mineral resources is an
      emerging research area that aims to design and develop efficient microbial
      formulations which are highly compatible with mineral inputs, with positive
      impacts on both crops and environment. This novel approach is likely to be of a
      global interest, especially in most N- and P-deficient agro-ecosystems. In this
      review, we report on the importance of NF bacteria and P solubilizing/mobilizing
      microbes as well as their interactions with mineral P fertilization in improving
      crop productivity and fertilizers efficiency. In addition, we shed light on the
      interactive and synergistic effects that may occur within multi-trophic
      interactions involving those two microbial groups and positive consequences on
      plant mineral uptake, crop productivity, and resiliency to environmental
      constraints. Improving use of mineral nutrients is a must to securing higher
      yield and productivity in a sustainable manner, therefore continuously designing,
      developing and testing innovative integrated plant nutrient management systems
      based on relevant biological resources (crops and microorganisms) is highly
      required.

PMID- 30108556
TI  - A Hypothetical Bottleneck in the Plant Microbiome.
AB  - The plant microbiome may be bottlenecked at the level of endophytes of individual
      seeds. Strong defense of developing seeds is predicted by optimal defense theory,
      and we have experimentally demonstrated exclusionary interactions among
      endophytic microbes infecting individual seeds of Centaurea stoebe. Having found
      a single, PDA-culturable microbe per seed or none in an exploratory study with
      Centaurea stoebe, we completed a more extensive survey of an additional 98 plant
      species representing 39 families. We again found that individual, surface
      sterilized seeds of all species hosted only one PDA-culturable bacterial or
      fungal endophyte per seed, or none. PDA-unculturables were not determined but we
      expect them to also be bottlenecked in individual seeds, as they too should be
      governed by exclusionary interactions. If the bottleneck were confirmed with high
      throughput sequencing of individual seeds then it would make sense to further
      investigate the Primary Symbiont Hypothesis (PSH). This includes the prediction
      that primary symbionts (i.e., the winners of the exclusionary battles among seed
      endophytes) have strong effects on seedlings depending on symbiont identity.

PMID- 30108555
TI  - Molecular Identification of Multidrug-Resistant Campylobacter Species From
      Diarrheal Patients and Poultry Meat in Shanghai, China.
AB  - Emerging resistance to the antimicrobial agents of choice for treatment of
      thermophilic Campylobacter infections is becoming a serious threat to public
      health. In this study, 548 Campylobacter (372 C. jejuni and 176 C. coli) isolates
      from diarrheal patients and poultry meat were subjected for antibiotic
      susceptibility analysis to ciprofloxacin, tetracycline, gentamicin, erythromycin
      and clindamycin. Among them, 151 Campylobacter (32 C. jejuni and 119 C. coli)
      were identified as multidrug resistant isolates. PFGE analysis was performed on
      the 151 multidrug resistant isolates to determine their genetic relatedness, and
      103 PFGE genotypes were determined. Some isolates from both human and chicken
      belonged to identical genotypes, indicating these clones might be able to spread
      between human and chicken. Antibiotic resistant genes of the 151 isolates were
      identified. The numbers of isolates carried tet (O), aadE, ermB, and aadE-sat4
      aphA were 148 (98%), 89 (58.9%), 31 (20.5%), and 10 (6.6%), respectively. Almost
      all (n = 150, 99.3%) had gyrA mutation at codon 86. And the 23s rRNA A2075G point
      mutation was found in 56 (37.1%) isolates. Gene mutations at the cmeR-cmeABC
      intergenic region may lead to the activation of CmeABC multidrug efflux pump, and
      in this study novel sequence types of the intergenic region were identified in
      both C. jejuni and C. coli. This study determined the genetic prerequisites for
      antibiotic resistance of multidrug resistant Campylobacter isolates from
      diarrheal patients and poultry meat in Shanghai, China.

PMID- 30108557
TI  - Type M Resistance to Macrolides Is Due to a Two-Gene Efflux Transport System of
      the ATP-Binding Cassette (ABC) Superfamily.
AB  - The mef(A) gene was originally identified as the resistance determinant
      responsible for type M resistance to macrolides, a phenotype frequently found in
      clinical isolates of Streptococcus pneumoniae and Streptococcus pyogenes. MefA
      was defined as a secondary transporter of the major facilitator superfamily
      driven by proton-motive force. However, when characterizing the mef(A)-carrying
      elements Tn1207.1 and Phi1207.3, another macrolide resistance gene, msr(D), was
      found adjacent to mef(A). To define the respective contribution of mef(A) and
      msr(D) to macrolide resistance, three isogenic deletion mutants were constructed
      by transformation of a S. pneumoniae strain carrying Phi1207.3: (i) Deltamef(A)
      Deltamsr(D); (ii) Deltamef(A)-msr(D); and (iii) mef(A)-Deltamsr(D).
      Susceptibility testing of mutants clearly showed that msr(D) is required for
      macrolide resistance, while deletion of mef(A) produced only a twofold reduction
      in the minimal inhibitory concentration (MIC) for erythromycin. The contribution
      of msr(D) to macrolide resistance was also studied in S. pyogenes, which is the
      original host of Phi1207.3. Two isogenic strains of S. pyogenes were constructed:
      (i) FR156, carrying Phi1207.3, and (ii) FR155, carrying Phi1207.3/Deltamsr(D).
      FR155 was susceptible to erythromycin, whereas FR156 was resistant, with an MIC
      value of 8 MUg/ml. Complementation experiments showed that reintroduction of the
      msr(D) gene could restore macrolide resistance in Deltamsr(D) mutants.
      Radiolabeled erythromycin was retained by strains lacking msr(D), while msr(D)
      carrying strains showed erythromycin efflux. Deletion of mef(A) did not affect
      erythromycin efflux. This data suggest that type M resistance to macrolides in
      streptococci is due to an efflux transport system of the ATP-binding cassette
      (ABC) superfamily, in which mef(A) encodes the transmembrane channel, and msr(D)
      the two ATP-binding domains.

PMID- 30108558
TI  - The Role of Lipoproteins in Mycoplasma-Mediated Immunomodulation.
AB  - Mycoplasma infections, such as walking pneumonia or pelvic inflammatory diseases,
      are a major threat to public health. Despite their relatively small physical and
      genomic size, mycoplasmas are known to elicit strong host immune responses,
      generally inflammatory, while also being able to evade the immune system. The
      mycoplasma membrane is composed of approximately two-thirds protein and one-third
      lipid and contains several lipoproteins that are known to regulate host immune
      responses. Herein, the immunomodulatory effects of mycoplasma lipoproteins are
      reviewed. A better understanding of the immunomodulatory effects, both activating
      and evasive, of Mycoplasma surface lipoproteins will contribute to understanding
      mechanisms potentially relevant to mycoplasma disease vaccine development and
      treatment.

PMID- 30108559
TI  - A Review of Dynamic Modeling Approaches and Their Application in Computational
      Strain Optimization for Metabolic Engineering.
AB  - Mathematical modeling is a key process to describe the behavior of biological
      networks. One of the most difficult challenges is to build models that allow
      quantitative predictions of the cells' states along time. Recently, this issue
      started to be tackled through novel in silico approaches, such as the
      reconstruction of dynamic models, the use of phenotype prediction methods, and
      pathway design via efficient strain optimization algorithms. The use of dynamic
      models, which include detailed kinetic information of the biological systems,
      potentially increases the scope of the applications and the accuracy of the
      phenotype predictions. New efforts in metabolic engineering aim at bridging the
      gap between this approach and other different paradigms of mathematical modeling,
      as constraint-based approaches. These strategies take advantage of the best
      features of each method, and deal with the most remarkable limitation-the lack of
      available experimental information-which affects the accuracy and feasibility of
      solutions. Parameter estimation helps to solve this problem, but adding more
      computational cost to the overall process. Moreover, the existing approaches
      include limitations such as their scalability, flexibility, convergence time of
      the simulations, among others. The aim is to establish a trade-off between the
      size of the model and the level of accuracy of the solutions. In this work, we
      review the state of the art of dynamic modeling and related methods used for
      metabolic engineering applications, including approaches based on hybrid
      modeling. We describe approaches developed to undertake issues regarding the
      mathematical formulation and the underlying optimization algorithms, and that
      address the phenotype prediction by including available kinetic rate laws of
      metabolic processes. Then, we discuss how these have been used and combined as
      the basis to build computational strain optimization methods for metabolic
      engineering purposes, how they lead to bi-level schemes that can be used in the
      industry, including a consideration of their limitations.

PMID- 30108560
TI  - Contrasting Soil Bacterial Community, Diversity, and Function in Two Forests in
      China.
AB  - Bacteria are the highest abundant microorganisms in the soil. To investigate
      bacteria community structures, diversity, and functions, contrasting them in four
      different seasons all the year round with/within two different forest type soils
      of China. We analyzed soil bacterial community based on 16S rRNA gene sequencing
      via Illumina HiSeq platform at a temperate deciduous broad-leaved forest
      (Baotianman, BTM) and a tropical rainforest (Jianfengling, JFL). We obtained
      51,137 operational taxonomic units (OTUs) and classified them into 44 phyla and
      556 known genera, 18.2% of which had a relative abundance >1%. The composition in
      each phylum was similar between the two forest sites. Proteobacteria and
      Acidobacteria were the most abundant phyla in the soil samples between the two
      forest sites. The Shannon index did not significantly differ among the four
      seasons at BTM or JFL and was higher at BTM than JFL in each season. The bacteria
      community at both BTM and JFL showed two significant (P < 0.05) predicted
      functions related to carbon cycle (anoxygenic photoautotrophy sulfur oxidizing
      and anoxygenic photoautotrophy) and three significant (P < 0.05) predicted
      functions related to nitrogen cycle (nitrous denitrificaton, nitrite
      denitrification, and nitrous oxide denitrification). We provide the basis on how
      changes in bacterial community composition and diversity leading to differences
      in carbon and nitrogen cycles at the two forests.

PMID- 30108561
TI  - Sublethal Photodynamic Treatment Does Not Lead to Development of Resistance.
AB  - A promising new alternative approach for eradication of antibiotic-resistant
      strains is to expose microbes to photosensitizers, which upon illumination
      generate reactive oxygen species. Among the requirements for a potent, medically
      applicable photosensitizer, are high efficacy in killing microbes and low
      toxicity to the host. Since photodynamic treatment is based on production of
      reactive species which are potentially DNA damaging and mutagenic, it might be
      expected that under selective pressure, microbes would develop resistance. The
      aim of this study was to determine if antibacterial photodynamic treatment with a
      highly photoefficient photosensitizer, Zn(II) meso-tetrakis(N-n-hexylpyridinium-2
      yl)porphyrin would lead to development of resistance. To answer that question,
      bacterial cultures were subjected to multiple cycles of sublethal photodynamic
      stress and regrowth, and to continuous growth under photodynamic exposure.
      Antibiotic-resistant Staphylococcus aureus and Escherichia coli clinical isolates
      were also tested for susceptibility to photodynamic inactivation and for
      development of resistance. Results demonstrated that multiple photodynamic
      exposures and regrowth of surviving cells or continuous growth under sublethal
      photodynamic conditions, did not lead to development of resistance to
      photosensitizers or to antibiotics. Antibiotic-resistant E. coli and S. aureus
      were as sensitive to photodynamic killing as were their antibiotic-sensitive
      counterparts and no changes in their sensitivity to antibiotics or to
      photodynamic inactivation after multiple cycles of photodynamic treatment and
      regrowth were observed. In conclusion, photosensitizers with high photodynamic
      antimicrobial efficiency can be used successfully for eradication of antibiotic
      resistant bacterial strains without causing development of resistance.

PMID- 30108562
TI  - Characterization of Bacteriophages Infecting Clinical Isolates of Clostridium
      difficile.
AB  - Clostridium difficile is recognized as a problematic pathogen, causing severe
      enteric diseases including antibiotic-associated diarrhea and pseudomembranous
      colitis. The emergence of antibiotic resistant C. difficile has driven a search
      for alternative anti-infection modalities. A promising strategy for controlling
      bacterial infection includes the use of bacteriophages and their gene products.
      Currently, knowledge of phages active against C. difficile is still relatively
      limited by the fact that the isolation of phages for this organism is a
      technically demanding method since bacterial host themselves are difficult to
      culture. To isolate and characterize phages specific to C. difficile, a genotoxic
      agent, mitomycin C, was used to induce temperate phages from 12 clinical isolates
      of C. difficile. Five temperate phages consisting of PhiHR24, PhiHN10, PhiHN16-1,
      PhiHN16-2, and PhiHN50 were successfully induced and isolated. Spotting assays
      were performed against a panel of 92 C. difficile isolates to screen for
      susceptible bacterial hosts. The results revealed that all the C. difficile
      phages obtained in this work displayed a relatively narrow host range of 0-6.5%
      of the tested isolates. Electron microscopic characterization revealed that all
      isolated phages contained an icosahedral head connected to a long contractile
      tail, suggesting that they belonged to the Myoviridae family. Restriction enzyme
      analysis indicated that these phages possess unique double-stranded DNA genome.
      Further electron microscopic characterization revealed that the PhiHN10 absorbed
      to the bacterial surface via attachment to cell wall, potentially interacting
      with S-layer protein. Bacteriophages isolated from this study could lead to
      development of novel therapeutic agents and detection strategies for C.
      difficile.

PMID- 30108563
TI  - Mixotrophy in Chlorophytes and Haptophytes-Effect of Irradiance, Macronutrient,
      Micronutrient and Vitamin Limitation.
AB  - Chlorophytes and haptophytes are key contributors to global phytoplankton biomass
      and productivity. Mixotrophic bacterivory has been detected for both groups, but
      a shortage of studies with cultured representatives hinders a consistent picture
      of the ecological relevance and regulation of this trophic strategy. Here, the
      growth, primary production, fraction of feeding cells (acidotropic probes) and
      bacterivory rates (surrogate prey) are tested for two species of the chlorophyte
      genus Nephroselmis and the haptophyte Isochrysis galbana under contrasting
      regimes of light (high vs. low) and nutrients (non-limited and macronutrient-,
      micronutrient- and vitamin-limited), at low bacterial concentrations (<107
      bacteria mL-1). All three species were obligate phototrophs, unable to compensate
      for low light conditions through feeding. Under nutrient limitation, N. rotunda
      and I. galbana fed, but growth ceased or was significantly lower than in the
      control. Thus, mixotrophic bacterivory could be a survival rather than a growth
      strategy for certain species. In contrast, nutrient-limited N. pyriformis
      achieved growth rates equivalent to the control through feeding. This strikingly
      differs with the classical view of chlorophytes as primarily non-feeders and
      indicates mixotrophic bacterivory can be a significant trophic strategy for green
      algae, even at the low bacterial concentrations found in oligotrophic open
      oceans.

PMID- 30108564
TI  - Listeria monocytogenes Colonizes Pseudomonas fluorescens Biofilms and Induces
      Matrix Over-Production.
AB  - In food facilities, biofilms or their debris might act as helpers for attracting
      free floating microorganisms. In this sense, Pseudomonas fluorescens, a dense
      biofilm producer frequently isolated from food contact surfaces, could be a good
      candidate for sheltering other microorganisms, such as Listeria monocytogenes.
      The main objective of this work was to evaluate the ability of L. monocytogenes
      to colonize pre-established Pseudomonas biofilms. For this, the movement
      throughout mature Pseudomonas biofilms of a green fluorescent protein (GFP) -
      tagged strain of L. monocytogenes was tracked for 24 h by confocal laser scanning
      microscopy (CLSM). Moreover, in order to check the effect of the incorporation of
      Listeria on the overall matrix production, attached populations of both
      microorganisms and total biomass (cells + matrix) of the resulting biofilms were
      measured over time. Planktonic cells of L. monocytogenes efficiently migrated to
      preformed P. fluorescens biofilms. Moreover, they moved preferentially toward the
      bottom layers of these structures, suggesting some kind of tropism. When
      preformed P. fluorescens biofilms were conditioning the surfaces, the L.
      monocytogenes attached population was on average, 1-2 Log higher than when this
      organism grew on bare coupons. Furthermore, the arrival of L. monocytogenes to
      the already established P. fluorescens biofilms led to a matrix over-production.
      Indeed, biomass values [optical density (OD595nm)] of the resulting biofilms were
      double those of the ordinary L. monocytogenes-P. fluorescens mixed biofilms (1.40
      vs. 0.6). The fact that L. monocytogenes cells accumulate in the bottom layers of
      preformed biofilms provides this microorganism an extra protection toward
      physical-chemical damages. This might partly explain why this microorganism can
      persist in food industry environments.

PMID- 30108565
TI  - Cronobacter sakazakii and Microbiological Parameters in Dairy Formulas Associated
      With a Food Alert in Chile.
AB  - The objective of this study was to evaluate the presence of Cronobacter sakazakii
      and microbiological parameters in dairy products associated with a food alert.
      Ninety dairy product samples were analyzed, including seven commercial brands and
      two product types (liquid and powdered) from four countries. Aerobic plate count
      (APC) and Enterobacteriaceae count were performed according to Chilean standards.
      Cronobacter spp. and C. sakazakii were identified by polymerase chain reaction
      real time amplification of rpoB and cgcA genes and the genotype by multilocus
      sequence typing. Eighty-eight percent of dairy products showed APC higher than
      the detection limit. Fifty percent of liquid commercial brand samples contained
      APC: 2.6, 2.3, 1.1, and 2.9 CFU/mL in brands A, C, E, and G, respectively.
      Results for powdered commercial brands were 3.0, 3.6, and 5.7 CFU/g in brands B,
      D, and F, respectively. Maximum count (5.7 CFU/g) occurred in brand F dairy
      product manufactured in Chile. Enterobacteriaceae were found in 55% of the
      samples, 64% in liquid and 51% in powdered commercial brands. In 50% of brands B,
      D, and E, samples contained 2.9, 2.8, and 2.7 log CFU/g, respectively. Only
      liquid commercial brands from the United States had Enterobacteriaceae values
      between 0.1 and 4.5 CFU/mL. Seventeen suspicious strains were isolated and nine
      were identified as Enterobacter spp. Only eight suspicious strains from four
      powdered commercial brands (Chile and Singapore) were confirmed as C. sakazakii
      by rpoB and cgcA gene amplification and fusA sequencing. C. sakazakii prevalence
      in the analyzed samples was 8.8%. There were 11% of powdered milk brands that
      contained APC between 4.0 and 4.7 log CFU/g and 55% of the samples contained
      Enterobacteriaceae. C. sakazakii was found in dairy products manufactured in
      Chile and Singapore. On the basis of this information, the Chilean Ministry of
      Health (RSA) decreed a national and international food alert and recalled all the
      product batches that resulted positive in the present study from supermarkets and
      pharmacies.

PMID- 30108567
TI  - Detection of New Quorum Sensing N-Acyl Homoserine Lactones From Aeromonas
      veronii.
AB  - Sturgeon is an important fresh water-culture fish in China. A problem with
      sturgeon is its high susceptibility to spoilage. Food spoilage is reported to be
      regulated by quorum sensing (QS). To identify the QS signals acetylated
      homoserine lactones (AHLs) in sturgeon and test whether QS plays a role in the
      spoilage of sturgeon, we investigated the specific spoilage organisms (SSOs) in
      vacuum packaged sturgeon stored at 4 degrees C and the production of AHLs by
      sturgeon SSOs. 16S rDNA sequencing and spoilage capabilities analysis revealed
      that Aeromonas veronii LP-11, Citrobacter freundii LPJ-2, and Raoultella
      ornithinolytica LPC-3 were the SSOs in sturgeon. Among the three SSOs, only A.
      veronii LP-11 induced the QS biosensors Agrobacterium tumefaciens KYC55 and
      Chromobacterium violaceum CV026, suggesting that it produced AHLs. Analysis by
      thin layer chromatography, high-performance liquid chromatography-triple
      quadrupole tandem mass spectrometry, and high-performance liquid chromatography
      quadrupole time-of-flight mass spectrometry (HPLC/qTOF-MS) identified that the
      AHLs produced by A. veronii were C6-SHL, C8-HSL, 3-oxo-C8-HSL, and 3-OH-C8-HSL.
      Our study revealed that QS system was probably involved in the regulation of
      sturgeon spoilage and for the first time reported the production of C8-HSL and 3
      OH-C8-HSL by genus Aeromonas. As only HPLC/qTOF-MS effectively and accurately
      identified all the four AHLs produced by A. veronii LP-11, this study also showed
      that HPLC/qTOF-MS was the most efficient method for rapid analysis of AHLs in
      complex microbial sample. The study provides new insight into the microbiology of
      sturgeon spoilage which may be helpful for better sturgeon preservation.

PMID- 30108566
TI  - Do Ruminal Ciliates Select Their Preys and Prokaryotic Symbionts?
AB  - Ruminal ciliates both preys on and form symbiotic relationships with other
      members of the ruminal microbiota for their survival. However, it remains elusive
      if they have selectivity over their preys or symbionts. In the present study, we
      investigated the above selectivity by identifying and comparing the free-living
      prokaryotes (FLP) and the ciliate-associated prokaryotes (CAP) using Illumina
      MiSeq sequencing of 16S rRNA gene amplicons. We used single ciliates cells of
      both monocultures of Entodinium caudatum and Epidinium caudatum and eight
      different ciliate genera isolated from fresh rumen fluid of dairy cows.
      Irrespective of the source (laboratory monocultures vs. fresh isolates) of the
      single ciliate cells, the CAP significantly differed from the FLP in microbiota
      community profiles. Many bacterial taxa were either enriched or almost
      exclusively found in the CAP across most of the ciliate genera. A number of
      bacteria were also found for the first time as ruminal bacteria in the CAP.
      However, no clear difference was found in methanogens between the CAP and the
      FLP, which was confirmed using methanogen-specific qPCR. These results suggest
      that ruminal ciliates probably select their preys and symbionts, the latter of
      which has rarely been found among the free-living ruminal prokaryotes. The
      bacteria enriched or exclusively found in the CAP can be target bacteria to
      detect and localize using specific probes designed from their 16S rRNA sequences,
      to characterize using single-cell genomics, or to isolate using new media
      designed based on genomic information.

PMID- 30108568
TI  - Resistance and Recovery of Methane-Oxidizing Communities Depends on Stress Regime
      and History; A Microcosm Study.
AB  - Although soil microbes are responsible for important ecosystem functions, and
      soils are under increasing environmental pressure, little is known about their
      resistance and resilience to multiple stressors. Here, we test resistance and
      recovery of soil methane-oxidizing communities to two different, repeated,
      perturbations: soil drying, ammonium addition and their combination. In
      replicated soil microcosms we measured methane oxidation before and after
      perturbations, while monitoring microbial abundance and community composition
      using quantitative PCR assays for the bacterial 16S rRNA and pmoA gene, and
      sequencing of the bacterial 16S rRNA gene. Although microbial community
      composition changed after soil drying, methane oxidation rates recovered, even
      after four desiccation events. Moreover, microcosms subjected to soil drying
      recovered significantly better from ammonium addition compared to microcosms not
      subjected to soil drying. Our results show the flexibility of microbial
      communities, even if abundances of dominant populations drop, ecosystem functions
      can recover. In addition, a history of stress may induce changes in community
      composition and functioning, which may in turn affect its future tolerance to
      different stressors.

PMID- 30108569
TI  - Dietary l-arginine Supplementation Alleviates the Intestinal Injury and Modulates
      the Gut Microbiota in Broiler Chickens Challenged by Clostridium perfringens.
AB  - Our previous reports suggested that Dietary l-arginine supplementation attenuated
      gut injury of broiler chickens infected with Clostridium perfringens by enhancing
      intestinal immune responses, absorption and barrier function, but its effect on
      the gut microbiome of broiler chickens remains unclear. This experiment aimed at
      evaluating the effects of Dietary l-arginine supplementation on the gut bacterial
      community composition and function of broiler chickens challenged with C.
      perfringens. In total, 105 1-day-old male Arbor Acres broiler chickens were
      assigned to three groups: Control (CTL), C. perfringens-challenged (CP), and C.
      perfringens-challenged and fed diet supplemented with 0.3% l-arginine (ARGCP)
      groups. The challenge led to macroscopic and histomorphological gut lesions,
      decreased villus height and increased the number of Observed species, Shannon,
      Chao1 and ACE indices of ileal microbiota, whereas l-arginine addition reversed
      these changes. Moreover, the three treatments harbored distinct microbial
      communities (ANOSIM, P < 0.05). At the genus level, 24 taxa (e.g., Nitrosomonas
      spp., Coxiella spp., Ruegeria spp., and Thauera spp.) were significantly more
      abundant in CP group than in CTL group (P < 0.05), whereas the levels of 23
      genera of them were significantly decreased by l-arginine supplementation (P <
      0.05). The abundances of only 3 genera were different between CTL and ARGCP
      groups (P < 0.05). At the species level, the challenge promoted the relative
      abundance of Nitrospira sp. enrichment culture clone M1-9, Bradyrhizobium
      elkanii, Nitrospira bacterium SG8-3, and Pseudomonas veronii, which was reversed
      by l-arginine supplementation (P < 0.05). Furthermore, the challenge decreased
      the levels of Lactobacillus gasseri (P < 0.05). Predictive functional profiling
      of microbial communities by PICRUSt showed that compared with CP group, ARGCP
      group had enriched pathways relating to membrane transport, replication and
      repair, translation and nucleotide metabolism and suppressed functions
      corresponding to amino acid and lipid metabolisms (P < 0.05). The relative
      abundances of KEGG pathways in l-arginine-fed broilers were almost equal to those
      of the controls. In conclusion, l-arginine alleviated the gut injury and
      normalized the ileal microbiota of C. perfringens-challenged chickens to resemble
      that of unchallenged controls in terms of microbial composition and
      functionality.

PMID- 30108571
TI  - Identification and Discrimination of Salmonella enterica Serovar Gallinarum
      Biovars Pullorum and Gallinarum Based on a One-Step Multiplex PCR Assay.
AB  - Salmonella enterica serovar Gallinarum biovars Pullorum (S. Pullorum) and
      Gallinarum (S. Gallinarum) can result in pullorum disease and fowl typhoid in
      avian species, respectively, and cause considerable economic losses in poultry in
      many developing countries. Conventional Salmonella serotyping is a time
      consuming, labor-intensive and expensive process, and the two biovars cannot be
      distinguished using the traditional serological method. In this study, we
      developed a rapid and reliable one-step multiplex polymerase chain reaction (PCR)
      assay to simultaneously identify and discriminate the biovars Pullorum and
      Gallinarum. The multiplex PCR method focused on three specific genes, stn,
      I137_08605 and ratA. Based on bioinformatics analysis, we found that gene
      I137_08605 was present only in S. Pullorum and S. Gallinarum, and a region of
      difference in ratA was deleted only in S. Pullorum after comparison with that of
      S. Gallinarum and other Salmonella serovars. Three pairs of primers specific for
      the three genes were designed for the multiplex PCR system and their selectivity
      and sensitivity were determined. The multiplex PCR results showed that S.
      Pullorum and S. Gallinarum could be identified and discriminated accurately from
      all tested strains including 124 strains of various Salmonella serovars and 42
      strains of different non-Salmonella pathogens. In addition, this multiplex PCR
      assay could detect a minimum genomic DNA concentration of 67.4 pg/MUL, and 100
      colony forming units. The efficiency of the multiplex PCR was evaluated by
      detecting natural-occurring Salmonella isolates from a chicken farm. The results
      demonstrated that the established multiplex PCR was able to identify S.
      Gallinarum and S. Pullorum individually, with results being consistent with
      traditional serotyping and biochemical testing. These results demonstrated that a
      highly accurate and simple biovar-specific multiplex PCR assay could be performed
      for the rapid identification and discrimination of Salmonella biovars Gallinarum
      and Pullorum, which will be useful, particularly under massive screening
      situations.

PMID- 30108572
TI  - Quantitative Analysis of the Bacteria in Blepharitis With Demodex Infestation.
AB  - Bacterial infection or Demodex infestation has been reported to contribute to
      chronic blepharitis. The association between Demodex mites and bacterial flora in
      this disease remains to be elucidated. Fifty-six consecutive patients diagnosed
      with chronic blepharitis and 46 healthy volunteers were recruited for this study.
      Using specimens of three epilated eyelashes and lid margin swabs, Demodex were
      identified microscopically and bacteria were determined by cultures, followed by
      colony counting and mass spectrometry. We found 191 Demodex mites, 161 D.
      folliculorum and 30 D. brevis, in 45 patients. Correspondingly, 101 Demodex, 63
      D. folliculorum and 38 D. brevis, were found in 21 controls (p < 0.05, both).
      Bacterial culture-positivity was obtained in samples (eyelashes, lid margins, or
      both) from 54 patients and in eyelashes from 37 controls. The total colony counts
      and the incidences and colony counts of Propinibacterium acnes and Staphylococcus
      aureus from patients' eyelashes were significantly higher than that of the
      controls. Furthermore, bacterial colony counts in blepharitis patients' eyelashes
      with D. folliculorum were higher than that of controls with D. folliculorum (p <
      0.01). Similarly, P. acnes colonies increased significantly in patients'
      eyelashes with D. folliculorum (p < 0.05). These results suggest that D.
      folliculorum and P. acnes have a role in the occurrence of the chronic
      blepharitis. Further studies are required to reveal the relationship between
      these two organisms in blepharitis.

PMID- 30108570
TI  - Metagenomic Analysis of Bacteria, Fungi, Bacteriophages, and Helminths in the Gut
      of Giant Pandas.
AB  - To obtain full details of gut microbiota, including bacteria, fungi,
      bacteriophages, and helminths, in giant pandas (GPs), we created a comprehensive
      microbial genome database and used metagenomic sequences to align against the
      database. We delineated a detailed and different gut microbiota structures of
      GPs. A total of 680 species of bacteria, 198 fungi, 185 bacteriophages, and 45
      helminths were found. Compared with 16S rRNA sequencing, the dominant bacterium
      phyla not only included Proteobacteria, Firmicutes, Bacteroidetes, and
      Actinobacteria but also Cyanobacteria and other eight phyla. Aside from
      Ascomycota, Basidiomycota, and Glomeromycota, Mucoromycota, and Microsporidia
      were the dominant fungi phyla. The bacteriophages were predominantly dsDNA
      Myoviridae, Siphoviridae, Podoviridae, ssDNA Inoviridae, and Microviridae. For
      helminths, phylum Nematoda was the dominant. In addition to previously described
      parasites, another 44 species of helminths were found in GPs. Also, differences
      in abundance of microbiota were found between the captive, semiwild, and wild
      GPs. A total of 1,739 genes encoding cellulase, beta-glucosidase, and cellulose
      beta-1,4-cellobiosidase were responsible for the metabolism of cellulose, and
      128,707 putative glycoside hydrolase genes were found in bacteria/fungi. Taken
      together, the results indicated not only bacteria but also fungi, bacteriophages,
      and helminths were diverse in gut of giant pandas, which provided basis for the
      further identification of role of gut microbiota. Besides, metagenomics revealed
      that the bacteria/fungi in gut of GPs harbor the ability of cellulose and
      hemicellulose degradation.

PMID- 30108575
TI  - Environmental Variability and Cyanobacterial Blooms in a Subtropical Coastal
      Lagoon: Searching for a Sign of Climate Change Effects.
AB  - Cyanobacterial blooms in marine and freshwater environments may be favored by
      shifts in physical water column parameters due to warming under climate change.
      The Patos Lagoon (PL), a subtropical coastal environment in southern Brazil, is
      known for recurrent blooms of Microcystis aeruginosa complex (MAC). Here, we
      analyze the variability of these blooms and their relation to changes in wind
      direction and speed, rainfall and freshwater run-off from 2000 to 2017. Also, we
      discuss both longer time-series of air temperature and rainfall and a review of
      local studies with microcystins produced by these noxious species. Since the
      1980s, MAC blooms were associated to negative anomalies in annual precipitation
      that occur during La Nina periods and, in the last years (2001-2014), accompanied
      by a trend in low river discharge. MAC blooms were conspicuous from December to
      March, i.e., austral summer, with massive patches seen in satellite images as for
      2017. We suggest that low rainfall and run-off years under NE wind-driven
      hydrodynamics might accumulate MAC biomass in the west margin of the PL system.
      In contrast, a positive, long-term trend in precipitation (from 1950 to 2016;
      slope = 3.9868 mm/yr, p < 0.05) should imply in high river discharge and,
      consequently, advection of this biomass to the adjacent coastal region. Due to
      the proximity to urban areas, the blooms can represent recreational and economic
      hazards to the region.

PMID- 30108573
TI  - Infection Kinetics and Tropism of Borrelia burgdorferi sensu lato in Mouse After
      Natural (via Ticks) or Artificial (Needle) Infection Depends on the Bacterial
      Strain.
AB  - Borrelia burgdorferi sl is a complex of pathogen bacteria transmitted to the host
      by Ixodes ticks. European Ixodes ricinus ticks transmit different B. burgdorferi
      species, pathogenic to human. Bacteria are principally present in unfed tick
      midgut, then migrate to salivary glands during blood meal and infect a new host
      via saliva. In this study, efficiency of transmission in a mouse model of three
      pathogen species belonging to the B. burgdorferi sl complex, B. burgdorferi sensu
      stricto (B31, N40, and BRE-13), B. afzelii (IBS-5), and B. bavariensis (PBi) is
      examined in order to evaluate infection risk after tick bite. We compared the
      dissemination of the Borrelia species in mice after tick bite and needle
      injection. Location in the ticks and transmission to mice were also determined
      for the three species by following infection kinetics. After inoculation, we
      found a significant prevalence in the brain for PBi and BRE-13, in the heart, for
      PBi, in the skin where B31 was more prevalent than PBi and in the ankle where
      both B31 and N40 were more present than PBi. After tick bite, statistical
      analyses showed that BRE-13 was more prevalent than N40 in the brain, in the
      bladder and in the inguinal lymph node. When Borrelia dissemination was compared
      after inoculation and tick bite, we observed heart infection only after tick
      inoculation of BRE-13, and PBi was only detected after tick bite in the skin. For
      N40, a higher number of positive organs was found after inoculation compared to
      tick bite. All European B. burgdorferi sl strains studied were detected in female
      salivary glands before blood meal and infected mice within 24 h of tick bite.
      Moreover, Borrelia-infected nymphs were able to infect mice as early as 12 h of
      tick attachment. Our study shows the need to remove ticks as early as possible
      after attachment. Moreover, Borrelia tropism varied according to the strain as
      well as between ticks bite and needle inoculation, confirming the association
      between some strains and clinical manifestation of Lyme borreliosis, as well as
      the role played by tick saliva in the efficiency of Borrelia infection and
      dissemination in vertebrates.

PMID- 30108574
TI  - Chestnut Honey and Bacteriophage Application to Control Pseudomonas aeruginosa
      and Escherichia coli Biofilms: Evaluation in an ex vivo Wound Model.
AB  - Chronic skin wounds represent a major burn both economically and socially.
      Pseudomonas aeruginosa and Escherichia coli are among the most common colonizers
      of infected wounds and are prolific biofilm formers. Biofilms are a major problem
      in infections due to their increasingly difficult control and eradication, and
      tolerance to multiple prescribed drugs. As so, alternative methods are necessary.
      Bacteriophages (phages) and honey are both seen as a promising approach for
      biofilm related infections. Phages have specificity toward a bacterial genus,
      species or even strain, self-replicating nature, and avoid dysbiosis. Honey has
      gained acknowledgment due to its antibacterial, antioxidant and anti-inflammatory
      and wound healing properties. In this work, the effect of E. coli and P.
      aeruginosa phages vB_EcoS_CEB_EC3a and vB_PaeP_PAO1-D and chestnut honey, alone
      and combined, were tested using in vitro (polystyrene) and ex vivo (porcine skin)
      models and against mono and dual-species biofilms of these bacteria. In general,
      colonization was higher in the porcine skins and the presence of a second
      microorganism in a consortium of species did not affect the effectiveness of the
      treatments. The antibacterial effect of combined therapy against dual-species
      biofilms led to bacterial reductions that were greater for biofilms formed on
      polystyrene than on skin. Monospecies biofilms of E. coli were better destroyed
      with phages and honey than P. aeruginosa monospecies biofilms. Overall, the
      combined phage-honey formulations resulted in higher efficacies possibly due to
      honey's capacity to damage the bacterial cell membrane and also to its ability to
      penetrate the biofilm matrix, promoting and enhancing the subsequent phage
      infection.

PMID- 30108576
TI  - The HIV-1 Subtype B Epidemic in French Guiana and Suriname Is Driven by Ongoing
      Transmissions of Pandemic and Non-pandemic Lineages.
AB  - The HIV-1 subtype B epidemic in French Guiana and Suriname is characterized by
      the co-circulation of the globally disseminated "BPANDEMIC" lineage and of non
      pandemic subtype B lineages of Caribbean origin (BCAR). To reconstruct the
      spatiotemporal pattern of spread of those viral lineages circulating in these two
      countries, a total of 361 HIV-1 subtype B pol sequences recovered from treatment
      naive adult patients from French Guiana and Suriname between 2006 and 2012 were
      combined with BPANDEMIC and BCAR reference sequences. Major Guianese/Surinamese
      BPANDEMIC and BCAR lineages were identified by Maximum Likelihood phylogenetic
      analysis and the spatiotemporal and demographic parameters estimated using a
      Bayesian coalescent-based method. We detected four BCAR and three BPANDEMIC
      transmission chains of large size that together comprise most pandemic and non
      pandemic subtype B sequences from French Guiana (>=52%) and Suriname (>=70%) here
      analyzed. These major lineages were probably introduced into French Guiana and
      Suriname from the Caribbean (BCAR) and North/South America (BPANDEMIC) between
      the middle 1970s and the late 1980s and spread among populations from both
      countries with roughly comparable demographic growth rates. We detected a
      significant trend for higher viral loads and higher proportion of
      homosexual/bisexual men among subjects infected with BPANDEMIC relative to BCAR
      strains in French Guiana. These results show that the HIV subtype B epidemic in
      French Guiana and Suriname has been driven by multiple active BCAR and BPANDEMIC
      transmission chains that arose since the middle 1970s onward and operate in both
      countries simultaneously. Although no significant differences in the epidemic
      potential of major BCAR and BPANDEMIC lineages were observed, relevant
      associations between the infecting subtype B lineage and epidemiological and
      clinical characteristics were detected in French Guiana.

PMID- 30108577
TI  - New Insights Into Functions and Possible Applications of Clostridium difficile
      CRISPR-Cas System.
AB  - Over the last decades the enteric bacterium Clostridium difficile (novel name
      Clostridioides difficile) - has emerged as an important human nosocomial
      pathogen. It is a leading cause of hospital-acquired diarrhea and represents a
      major challenge for healthcare providers. Many aspects of C. difficile
      pathogenesis and its evolution remain poorly understood. Efficient defense
      systems against phages and other genetic elements could have contributed to the
      success of this enteropathogen in the phage-rich gut communities. Recent studies
      demonstrated the presence of an active CRISPR (clustered regularly interspaced
      short palindromic repeats)-Cas (CRISPR-associated) subtype I-B system in C.
      difficile. In this mini-review, we will discuss the recent advances in
      characterization of original features of the C. difficile CRISPR-Cas system in
      laboratory and clinical strains, as well as interesting perspectives for our
      understanding of this defense system function and regulation in this important
      enteropathogen. This knowledge will pave the way for the development of promising
      biotechnological and therapeutic tools in the future. Possible applications for
      the C. difficile strain monitoring and genotyping, as well as for CRISPR-based
      genome editing and antimicrobials are also discussed.

PMID- 30108578
TI  - Concentration and Community of Airborne Bacteria in Response to Cyclical Haze
      Events During the Fall and Midwinter in Beijing, China.
AB  - Since 2013, severe haze events frequently have occurred in Beijing between
      October and March, which have created a significant public health threat.
      Although variations in the chemical composition of these haze events have been
      studied widely, information pertaining to airborne bacteria in such haze events
      remains limited. In this study, we characterized the concentration, community
      structure, and composition of the airborne bacteria in response to nine haze
      events that occurred between October 1, 2015, and January 5, 2016. We also
      analyzed the correlations of airborne bacteria (concentration, community
      structure, and composition) with pollution levels and meteorological factors. The
      results indicated that airborne bacterial concentration showed a positive
      cyclical correlation with the haze events, but the bacterial concentration
      plateaued at the yellow pollution level. In addition, we found particulate matter
      (PM10) and relative humidity to be key factors that significantly affected the
      airborne bacterial concentration and community structure. Moreover, Halomonas and
      Shewanella were enriched on haze days for all nine of the haze events. Finally,
      the correlations between haze pollution and airborne bacteria in midwinter were
      weaker than those in fall and early winter, indicating an obvious staged
      distinction among the effects of haze on airborne bacteria. Our study illuminated
      the dynamic variation of bioaerosols corresponding to the cyclical haze events
      and revealed the interactions among air pollution, climate factors (mainly
      relative humidity), and airborne bacteria. These results imply that different
      strategies should be applied to deal with the potential threat of airborne
      bacteria during haze events in different seasons.

PMID- 30108579
TI  - Gut Microbiota in Tibetan Herdsmen Reflects the Degree of Urbanization.
AB  - Urbanization is associated with shifts in human lifestyles, thus possibly
      influencing the diversity, interaction and assembly of gut microbiota. However,
      the question regarding how human gut microbiota adapts to varying lifestyles
      remains elusive. To understand the relationship between gut microbiota and
      urbanization, we compared the diversity, interaction and assembly of gut
      microbial communities of herdsmen from three regions with different levels of
      urbanization, namely traditional herdsmen (TH), semi-urban herdsmen (SUH) and
      urban herdsmen (UH). The relative abundance of Prevotella decreased with the
      degree of urbanization (from TH to UH), whereas that of Bacteroides,
      Faecalibacterium, and Blautia showed an opposite trend. Although the alpha
      diversity measures (observed OTUs and phylogenetic diversity) of gut microbiota
      were unaffected by urbanization, the beta diversity (Jaccard or Bray-Curtis
      distances) was significantly influenced by urbanization. Metagenome prediction
      revealed that the gene functions associated with metabolism (i.e., carbohydrate
      and lipid metabolism) had significant differences between TH and UH. Network
      analysis showed that the modularity increased with the degree of urbanization,
      indicating a high extent of niche differentiation in UH. Meanwhile the trend of
      network density was opposite, indicating a more complex network in TH. Notably,
      the relative importance of environmental filtering that governed the community
      assembly increased with the degree of urbanization, which indicated that
      deterministic factors (e.g., low-fiber diet) play more important roles than
      stochastic factors (e.g., stochastic dispersal) in shaping the gut microbiota. A
      quantification of ecological processes showed a stronger signal of variable
      selection in UH than TH, implying that different selective pressures cause
      divergent gut community compositions due to urban lifestyles. Our results suggest
      that beta diversity, network interactions and ecological processes of gut
      microbiota may reflect the degree of urbanization, and highlight the adaptation
      of human gut microbiota to lifestyle changes.

PMID- 30108580
TI  - Plant and Microbial Responses to Repeated Cu(OH)2 Nanopesticide Exposures Under
      Different Fertilization Levels in an Agro-Ecosystem.
AB  - The environmental fate and potential impacts of nanopesticides on agroecosystems
      under realistic agricultural conditions are poorly understood. As a result, the
      benefits and risks of these novel formulations compared to the conventional
      products are currently unclear. Here, we examined the effects of repeated
      realistic exposures of the Cu(OH)2 nanopesticide, Kocide 3000, on simulated
      agricultural pastureland in an outdoor mesocosm experiment over 1 year. The
      Kocide applications were performed alongside three different mineral
      fertilization levels (Ambient, Low, and High) to assess the environmental impacts
      of this nanopesticide under low-input or conventional farming scenarios. The
      effects of Kocide over time were monitored on forage biomass, plant mineral
      nutrient content, plant-associated non-target microorganisms (i.e., N-fixing
      bacteria or mycorrhizal fungi) and six soil microbial enzyme activities. We
      observed that three sequential Kocide applications had no negative effects on
      forage biomass, root mycorrhizal colonization or soil nitrogen fixation rates. In
      the Low and High fertilization treatments, we observed a significant increase in
      aboveground plant biomass after the second Kocide exposure (+14% and +27%,
      respectively). Soil microbial enzyme activities were significantly reduced in the
      short-term after the first exposure (day 15) in the Ambient (-28% to -82%) and
      Low fertilization (-25% to -47%) but not in the High fertilization treatment.
      However, 2 months later, enzyme activities were similar across treatments and
      were either unresponsive or responded positively to subsequent Kocide additions.
      There appeared to be some long-term effects of Kocide exposure, as 6 months after
      the last Kocide exposure (day 365), both beta-glucosidase (-57% in Ambient and 
      40% in High fertilization) and phosphatase activities (-47% in Ambient
      fertilization) were significantly reduced in the mesocosms exposed to the
      nanopesticide. These results suggest that when used in conventional farming with
      high fertilization rates, Kocide applications did not lead to marked adverse
      effects on forage biomass production and key plant-microorganism interactions
      over a growing season. However, in the context of low-input organic farming for
      which this nanopesticide is approved, Kocide applications may have some
      unintended detrimental effects on microbially mediated soil processes involved in
      carbon and phosphorus cycling.

PMID- 30108581
TI  - Excision and Circularization of Integrative Conjugative Element Tn5253 of
      Streptococcus pneumoniae.
AB  - The integrative conjugative element (ICE) Tn5253 of Streptococcus pneumoniae,
      conferring resistance to tetracycline and chloramphenicol, was found integrated
      at a 83-bp specific target site (attB) located in the rbgA gene of the
      pneumococcal chromosome. PCR analysis of Tn5253-carrying strains showed evidence
      of precise excision of Tn5253 from the pneumococcal chromosome with production of
      (i) circular forms of the ICE in which the ends were joined by a 84-bp sequence
      (attTn), and (ii) reconstituted chromosomal attB. When integrated into the
      chromosome, Tn5253 was flanked by attL, identical to attB, and attR, identical to
      attTn. Circular forms of Tn5253 were present at a concentration of 3.8 * 10-4
      copies per chromosome, whereas reconstituted attB sites were at 3.0 * 10-4 copies
      per chromosome. Deletion of int-xis of Tn5253 abolished production of circular
      forms (<7.1 * 10-6 copies per chromosome) and was associated to the lack of
      Tn5253 conjugal transfer suggesting, as expected, that Tn5253 circular form acts
      as a conjugation intermediate.

PMID- 30108582
TI  - The Therapeutic and Pathogenic Role of Autophagy in Autoimmune Diseases.
AB  - Autophagy is a complicated cellular mechanism that maintains cellular and tissue
      homeostasis and integrity via degradation of senescent, defective subcellular
      organelles, infectious agents, and misfolded proteins. Accumulating evidence has
      shown that autophagy is involved in numerous immune processes, such as removal of
      intracellular bacteria, cytokine production, autoantigen presentation, and
      survival of lymphocytes, indicating an apparent and important role in innate and
      adaptive immune responses. Indeed, in genome-wide association studies, autophagy
      related gene polymorphisms have been suggested to be associated with the
      pathogenesis of several autoimmune and inflammatory disorders, such as systemic
      lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory bowel disease,
      and multiple sclerosis. In addition, conditional knockdown of autophagy-related
      genes in mice displayed therapeutic effects on several autoimmune disease models
      by reducing levels of inflammatory cytokines and autoreactive immune cells.
      However, the inhibition of autophagy accelerates the progress of some
      inflammatory and autoimmune diseases via promotion of inflammatory cytokine
      production. Therefore, this review will summarize the current knowledge of
      autophagy in immune regulation and discuss the therapeutic and pathogenic role of
      autophagy in autoimmune diseases to broaden our understanding of the
      etiopathogenesis of autoimmune diseases and shed light on autophagy-mediated
      therapies.

PMID- 30108583
TI  - Galectin-3 and Galectin-9 May Differently Regulate the Expressions of Microglial
      M1/M2 Markers and T Helper 1/Th2 Cytokines in the Brains of Genetically
      Susceptible C57BL/6 and Resistant BALB/c Mice Following Peroral Infection With
      Toxoplasma gondii.
AB  - Toxoplasmic encephalitis (TE), an opportunistic infection, is a severe health
      problem in immunocompromised patients. Previous studies have revealed that
      C57BL/6 mice are susceptible and BALB/c mice are resistant to TE. To investigate
      the mechanisms involved in the immunopathogenesis of TE in susceptible C57BL/6
      and resistant BALB/c mice, both strains of mice were perorally infected with the
      Prugniuad (Pru) strain of Toxoplasma gondii. Our results showed that compared
      with BALB/c mice, C57BL/6 mice infected with T. gondii Pru strain had more severe
      brain histopathological damage, and higher mRNA expression levels of tachyzoite
      specific surface antigen 1, bradyzoite-specific antigen 1, interferon gamma
      (IFNgamma), interleukin (IL)-10, arginase1 (Arg1) (M2 marker), galectin (Gal)-3,
      Gal-9, T. gondii microneme protein 1 (TgMIC1), TgMIC4, and TgMIC6 during the
      course of infection by using quantitative real-time reverse transcription
      polymerase chain reaction. Further analysis displayed that BALB/c mice showed
      higher numbers of microglial cells and higher levels of IL-1beta, inducible
      nitric oxide synthase (iNOS) (M1 marker), and chitinase-3-like protein 3 (Ym1)
      (M2 marker) in the early infective stage [at day 14 or 35 post infection (p.i.)]
      compared with C57BL/6 mice, whereas C57BL/6 mice showed higher numbers of
      microglial cells and higher levels of IL-10, iNOS (M1 marker), and Ym1 (M2
      marker) at days 35, 50, or 70 p.i. compared with BALB/c mice. Correlation
      analysis showed that significant positive correlations existed between Gal-3 and
      IL-4/IL-10/iNOS/Ym1 and between Gal-9 and IL-4/Ym1 in C57BL/6 mice; between Gal-3
      and IFNgamma/Arg1 and between Gal-9 and IFNgamma/Arg1 in BALB/c mice. Together,
      our data demonstrated that different Gal-3 and Gal-9 expressions as well as
      different positive correlations were found between Gal-3 and T helper 1
      (Th1)/Th2/M1/M2 cytokines or between Gal-9 and Th1/Th2/M2 cytokines in the brains
      of T. gondii Pru strain-infected C57BL/6 and BALB/c mice.

PMID- 30108584
TI  - Immune Cell Hacking: Challenges and Clinical Approaches to Create Smarter
      Generations of Chimeric Antigen Receptor T Cells.
AB  - T cells equipped with chimeric antigen receptors (CAR T cells) have recently
      provided promising advances as a novel immunotherapeutic approach for cancer
      treatment. CAR T cell therapy has shown stunning results especially in B-cell
      malignancies; however, it has shown less success against solid tumors, which is
      more supposed to be related to the specific characteristics of the tumor
      microenvironment. In this review, we discuss the structure of the CAR, current
      clinical advantages from finished and ongoing trials, adverse effects, challenges
      and controversies, new engineering methods of CAR, and clinical considerations
      that are associated with CAR T cell therapy both in hematological malignancies
      and solid tumors. Also, we provide a comprehensive description of recently
      introduced modifications for designing smarter models of CAR T cells. Specific
      hurdles and problems that limit the optimal function of CAR T cells, especially
      on solid tumors, and possible solutions according to new modifications and
      generations of CAR T cells have been introduced here. We also provide information
      of the future directions on how to enhance engineering the next smarter
      generations of CAR T cells in order to decrease the adverse effects and increase
      the potency and efficacy of CAR T cells against cancer.

PMID- 30108585
TI  - Genealogy, Dendritic Cell Priming, and Differentiation of Tissue-Resident Memory
      CD8+ T Cells.
AB  - Tissue-resident memory CD8+ T (Trm) cells define a distinct non-recirculating
      subset. Trm cells constitute a first line of defense against local infections in
      barrier tissues, but they are also found in non-barrier tissues and play a role
      in antitumor immunity. Their differentiation in tissues and their phenotypical,
      transcriptional, and functional characteristics are the object of active
      research. Herein, we will discuss the potential existence of committed CD8+ Trm
      precursors and the genealogy of memory CD8+ T cell subsets. In addition to the
      priming of naive T cells, there is some plasticity of antigen-experienced
      effector and memory T cell subsets to generate Trm precursors. Local
      inflammation, antigen presentation, and cytokines drive Trm differentiation. It
      is of prime interest how specific dendritic cell subsets modulate priming and
      differentiation of Trm cells, as well as their reactivation within tissues.
      Research on how we can manipulate generation of memory T cells subsets is key for
      improved vaccination strategies.

PMID- 30108587
TI  - CL-L1 and CL-K1 Exhibit Widespread Tissue Distribution With High and Co-Localized
      Expression in Secretory Epithelia and Mucosa.
AB  - Collectin liver 1 (CL-L1, alias collectin 10) and collectin kidney 1 (CL-K1,
      alias collectin 11) are oligomeric pattern recognition molecules associated with
      the complement system, and mutations in either of their genes may lead to
      deficiency and developmental defects. The two collectins are reportedly localized
      and synthesized in the liver, kidneys, and adrenals, and can be found in the
      circulation as heteromeric complexes (CL-LK), which upon binding to microbial
      high mannose-like glycoconjugates activates the complement system via the lectin
      activation pathway. The tissue distribution of homo- vs. heteromeric CL-L1 and 
      K1 complexes, the mechanism of heteromeric complex formation and in which tissues
      this occurs, is hitherto incompletely described. We have by immunohistochemistry
      using monoclonal antibodies addressed the precise cellular localization of the
      two collectins in the main human tissues. We find that the two collectins have
      widespread and almost identical tissue distribution with a high expression in
      epithelial cells in endo-/exocrine secretory tissues and mucosa. There is also
      accordance between localization of mRNA transcripts and detection of proteins,
      showing that local synthesis likely is responsible for peripheral localization
      and eventual formation of the CL-LK complexes. The functional implications of the
      high expression in endo-/exocrine secretory tissue and mucosa is unknown but
      might be associated with the activity of MASP-3, which has a similar pattern of
      expression and is known to potentiate the activity of the alternative complement
      activation pathway.

PMID- 30108586
TI  - The Kaleidoscope of Microglial Phenotypes.
AB  - Gene expression analyses of microglia, the tissue-resident macrophages of the
      central nervous system (CNS), led to the identification of homeostatic as well as
      neurological disease-specific gene signatures of microglial phenotypes. Upon
      alterations in the neural microenvironment, either caused by local insults from
      within the CNS (during neurodegenerative diseases) or by macroenvironmental
      incidents, such as social stress, microglia can switch phenotypes-generally
      referred to as "microglial activation." The interplay between the
      microenvironment and its influence on microglial phenotypes, regulated by
      (epi)genetic mechanisms, can be imagined as the different colorful crystal
      formations (microglial phenotypes) that change upon rotation (microenvironmental
      changes) of a kaleidoscope. In this review, we will discuss microglial phenotypes
      in relation to neurodevelopment, homeostasis, in vitro conditions, aging, and
      neurodegenerative diseases based on transcriptome studies. By overlaying these
      disease-specific microglial signatures, recent publications have identified a
      specific set of genes that is differentially expressed in all investigated
      diseases, called a microglial core gene signature with multiple diseases. We will
      conclude this review with a discussion about the complexity of this microglial
      core gene signature associated with multiple diseases.

PMID- 30108589
TI  - Antitumor Activity of Extract From the Sporoderm-Breaking Spore of Ganoderma
      lucidum: Restoration on Exhausted Cytotoxic T Cell With Gut Microbiota
      Remodeling.
AB  - As breast cancer is the leading cause of cancer-related deaths in women
      population worldwide, ongoing endeavor has been made for alternative regimens
      with improved efficacy but fewer adverse effects. Recently, active components
      from the spores of Ganoderma lucidum have attracted much attention for their
      versatile biological activities owing to the advance in sporoderm-breaking
      technology. Here, anticancer potential of an extract derived from the sporoderm
      breaking spores of G. lucidum (ESG) was explored in a 4T1-breast cancer xenograft
      mice model. Results showed that ESG was able to suppress 4T1 tumor growth in vivo
      rather than in vitro. Flowcytometry analysis revealed that ESG could
      significantly increase both cytotoxic T cell (Tc) population and the ratio of Tc
      to helper T cell (Th) in peripheral blood of the tumor-bearing mouse; similar
      promotion on Tc was also found in tumor-infiltrating lymphocyte. Moreover, ESG
      evidently downregulated the two immune checkpoints, programmed cell death protein
      1 (PD-1, in the spleen) and cytotoxic T lymphocyte antigen-4 (CTLA-4, in the
      tumor), suggesting that ESG could effectively restore the T cell paradigm by
      recovering the exhaustion status via suppressing the co-inhibitory checkpoints.
      By 16S rRNA gene sequence analysis on the fecal microbiota, it was found that ESG
      would remodeling the overall structure of the samples from tumor-bearing mice
      toward that of the normal counterparts, including 18 genera in 5 phyla, together
      with regulations on several genes that are responsible for signaling pathways
      involved in metabolism, cellular processes, and environmental information
      processing. Collectively, this study demonstrated that ESG would serve as a
      natural anticancer adjuvant via a restoration on the exhausted Tc, highlighting
      important clinical implications for the treatment of breast cancer.

PMID- 30108590
TI  - Squamous Cell Carcinomas of the Head and Neck Cancer Response to Programmed Cell
      Death Protein-1 Targeting and Differential Expression of Immunological Markers: A
      Case Report.
AB  - Targeting the programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-L1) pathway
      has been shown to enhance T cell-mediated antitumor immunity. Clinical responses
      are limited to subgroups of patients. The search for biomarkers of response is a
      strategy to predict response and outcome of PD-1/PD-L1 checkpoint intervention.
      The NY-ESO-1 cancer testis antigen has been considered as a biomarker in head and
      neck squamous cell carcinoma (HNSCC) patients and can induce both specific NY-ESO
      1 antibody and T cells responses. Here, we correlated clinical responsiveness to
      anti-PD-1 (nivolumab) treatment with immunity to NY-ESO-1 in a patient with
      recurrent HNSCC. The patient was treated with second-line treatment of nivolumab
      and had a stable disease for over 7 months. His NY-ESO-1 antibody was found to be
      lower after the third (****p < 0.0001) and the fifth (****p < 0.0001) cycles of
      treatment compared to base line, and this was in line with the stability of the
      disease. The NY-ESO-1-specific T cells response of the patient was found to be
      increased after the third and the fifth (**p = 0.002) cycles of treatment but had
      a significant decline after progression (**p = 0.0028). The PD-1 expression by
      the patient's T cells was reduced 15-folds after nivolumab treatment and was
      uniquely restricted to the CD8+ T cells population. Several cytokines/chemokines
      involved in immune activation were upregulated after nivolumab treatment; two
      biomarkers were reduced at progression [interleukin (IL)-10: ****p < 0.0001 and
      CX3CL1: ****p < 0.0001]. On the other hand, some cytokines/chemokines
      contributing to immune inhibition were downregulated after nivolumab treatment;
      two biomarkers were increased at progression (IL-6: ****p < 0.0001 and IL-8:
      ****p < 0.0001). This data support the notion that the presence of anti-NY-ESO-1
      integrated immunity and some cytokines/chemokines profile may potentially
      identify a response to PD-1 blockade in HNSCC patients.

PMID- 30108591
TI  - Anti-Tumor Necrosis Factor alpha Therapeutics Differentially Affect Leishmania
      Infection of Human Macrophages.
AB  - Tumor necrosis factor alpha (TNFalpha) drives the pathophysiology of human
      autoimmune diseases and consequently, neutralizing antibodies (Abs) or Ab-derived
      molecules directed against TNFalpha are essential therapeutics. As treatment with
      several TNFalpha blockers has been reported to entail a higher risk of infectious
      diseases such as leishmaniasis, we established an in vitro model based on
      Leishmania-infected human macrophages, co-cultured with autologous T-cells, for
      the analysis and comparison of anti-TNFalpha therapeutics. We demonstrate that
      neutralization of soluble TNFalpha (sTNFalpha) by the anti-TNFalpha Abs
      Humira(r), Remicade(r), and its biosimilar Remsima(r) negatively affects
      infection as treatment with these agents significantly reduces Leishmania-induced
      T-cell proliferation and increases the number of infected macrophages. By
      contrast, we show that blockade of sTNFalpha by Cimzia(r) does not affect T-cell
      proliferation and infection rates. Moreover, compared to Remicade(r), treatment
      with Cimzia(r) does not impair the expression of cytolytic effector proteins in
      proliferating T-cells. Our data demonstrate that Cimzia(r) supports parasite
      control through its conjugated polyethylene glycol (PEG) moiety as PEGylation of
      Remicade(r) improves the clearance of intracellular Leishmania. This effect can
      be linked to complement activation, with levels of complement component C5a being
      increased upon treatment with Cimzia(r) or a PEGylated form of Remicade(r). Taken
      together, we provide an in vitro model of human leishmaniasis that allows direct
      comparison of different anti-TNFalpha agents. Our results enhance the
      understanding of the efficacy and adverse effects of TNFalpha blockers and they
      contribute to evaluate anti-TNFalpha therapy for patients living in countries
      with a high prevalence of leishmaniasis.

PMID- 30108592
TI  - Alveolar Macrophages in the Resolution of Inflammation, Tissue Repair, and
      Tolerance to Infection.
AB  - Pathogen persistence in the respiratory tract is an important preoccupation, and
      of particular relevance to infectious diseases such as tuberculosis. The
      equilibrium between elimination of pathogens and the magnitude of the host
      response is a sword of Damocles for susceptible patients. The alveolar macrophage
      is the first sentinel of the respiratory tree and constitutes the dominant immune
      cell in the steady state. This immune cell is a key player in the balance between
      defense against pathogens and tolerance toward innocuous stimuli. This review
      focuses on the role of alveolar macrophages in limiting lung tissue damage from
      potentially innocuous stimuli and from infections, processes that are relevant to
      appropriate tolerance of potential causes of lung disease. Notably, the different
      anti-inflammatory strategies employed by alveolar macrophages and lung tissue
      damage control are explored. These two properties, in addition to macrophage
      manipulation by pathogens, are discussed to explain how alveolar macrophages may
      drive pathogen persistence in the airways.

PMID- 30108588
TI  - A Role for Epitope Networking in Immunomodulation by Helminths.
AB  - Helminth infections, by nematodes, trematodes, or cestodes, can lead to the
      modulation of host immune responses. This allows long-duration parasite
      infections and also impacts responses to co-infections. Surface, secreted,
      excreted, and shed proteins are thought to play a major role in modulation. A
      commonly reported feature of such immune modulation is the role of T regulatory
      (Treg) cells and IL-10. Efforts to identify helminth proteins, which cause
      immunomodulation, have identified candidates but not provided clarity as to a
      uniform mechanism driving modulation. In this study, we applied a bioinformatics
      systems approach, allowing us to analyze predicted T-cell epitopes of 17 helminth
      species and the responses to their surface proteins. In addition to major
      histocompatibility complex (MHC) binding, we analyzed amino acid motifs that
      would be recognized by T-cell receptors [T-cell-exposed motifs (TCEMs)]. All the
      helminth species examined have, within their surface proteins, peptides, which
      combine very common TCEMs with predicted high affinity binding to many human MHC
      alleles. This combination of features would result in large cognate T cell and a
      high probability of eliciting Treg responses. The TCEMs, which determine
      recognition by responding T-cell clones, are shared to a high degree between
      helminth species and with Plasmodium falciparum and Mycobacterium tuberculosis,
      both common co-infecting organisms. The implication of our observations is not
      only that Treg cells play a significant role in helminth-induced immune
      modulation but also that the epitope specificities of Treg responses are shared
      across species and genera of helminth. Hence, the immune response to a given
      helminth cannot be considered in isolation but rather forms part of an epitope
      ecosystem, or microenvironment, in which potentially immunosuppressive peptides
      in the helminth network via their common T-cell receptor recognition signals with
      T-cell epitopes in self proteins, microbiome, other helminths, and taxonomically
      unrelated pathogens. Such a systems approach provides a high-level view of the
      antigen-immune system signaling dynamics that may bias a host's immune response
      to helminth infections toward immune modulation. It may indicate how helminths
      have evolved to select for peptides that favor long-term parasite host
      coexistence.

PMID- 30108593
TI  - PIP-EL: A New Ensemble Learning Method for Improved Proinflammatory Peptide
      Predictions.
AB  - Proinflammatory cytokines have the capacity to increase inflammatory reaction and
      play a central role in first line of defence against invading pathogens.
      Proinflammatory inducing peptides (PIPs) have been used as an antineoplastic
      agent, an antibacterial agent and a vaccine in immunization therapies. Due to the
      advancement in sequence technologies that resulted an avalanche of protein
      sequence data. Therefore, it is necessary to develop an automated computational
      method to enable fast and accurate identification of novel PIPs within the vast
      number of candidate proteins and peptides. To address this, we proposed a new
      predictor, PIP-EL, for predicting PIPs using the strategy of ensemble learning
      (EL). Our benchmarking dataset is imbalanced. Thus, we applied a random under
      sampling technique to generate 10 balanced models for each composition.
      Technically, PIP-EL is the fusion of 50 independent random forest (RF) models,
      where each of the five different compositions, including amino acid, dipeptide,
      composition-transition-distribution, physicochemical properties, and amino acid
      index contains 10 RF models. PIP-EL achieves the Matthews' correlation
      coefficient (MCC) of 0.435 in a 5-fold cross-validation test, which is ~2-5%
      higher than that of the individual classifiers and hybrid feature-based
      classifier. Furthermore, we evaluate the performance of PIP-EL on the independent
      dataset, showing that our method outperforms the existing method and two
      different machine learning methods developed in this study, with an MCC of 0.454.
      These results indicate that PIP-EL will be a useful tool for predicting PIPs and
      for researchers working in the field of peptide therapeutics and immunotherapy.
      The user-friendly web server, PIP-EL, is freely accessible.

PMID- 30108594
TI  - Immune Checkpoint-Mediated Interactions Between Cancer and Immune Cells in
      Prostate Adenocarcinoma and Melanoma.
AB  - Prostate adenocarcinoma (PCa) and melanoma are paradigmatic examples of tumors
      that are either poorly or highly sensitive to therapies based on monoclonal
      antibodies directed against regulatory pathways in T lymphocytes [i.e., immune
      checkpoint blockade (ICB)]. Yet, approximately 40% of melanoma patients are
      resistant or acquire resistance to ICB. What characterize the microenvironment of
      PCa and ICB-resistant melanoma are a scanty cytotoxic T cell infiltrate and a
      strong immune suppression, respectively. Here, we compare the tumor
      microenvironment in these two subgroups of cancer patients, focusing on some
      among the most represented immune checkpoint molecules: cytotoxic T lymphocyte
      associated antigen-4, programmed death-1, lymphocyte activation gene-3, and T
      cell immunoglobulin and mucin-domain containing-3. We also report on several
      examples of crosstalk between cancer and immune cells that are mediated by
      inhibitory immune checkpoints and identify promising strategies aimed at
      overcoming ICB resistance both in PCa and melanoma.

PMID- 30108595
TI  - Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy
      by Dectin-1-Activated Dendritic Cells.
AB  - We recently discovered that dectin-1-activated dendritic cells (DCs) drive potent
      T helper (Th) 9 cell responses and antitumor immunity. However, the underlying
      mechanisms need to be further defined. The cytokine microenvironment is critical
      for Th cell differentiation. Here, we show that dectin-1 activation enhances
      interleukin (IL)-33 expression in DCs. We found that blocking IL-33/ST2 inhibits
      dectin-1-activated DC-induced Th9 cell differentiation. More importantly, the
      addition of IL-33 further promotes Th9 cell priming and antitumor efficacy
      induced by dectin-1-activated DCs. Mechanistically, in addition to the promotion
      of Th9 and Th1 cells, dectin-1-activated DCs combined with IL-33 abolish the
      activity of IL-33 in the induction of regulatory T cells. Furthermore, the
      combined treatment of dectin-1-activated DCs and IL-33 increases the frequencies
      of CD4+ T cells by fostering their proliferation and inhibiting their exhaustive
      differentiation. Thus, our results demonstrate the important role of IL-33 in
      dectin-1-activated DC-induced Th9 cell differentiation and antitumor efficacy,
      and suggest that the combination of dectin-1-activated DCs and IL-33 may present
      a new effective modality of DC-based vaccines in tumor immunotherapy.

PMID- 30108597
TI  - Functional Specialization of Duplicated AGAMOUS Homologs in Regulating Floral
      Organ Development of Medicago truncatula.
AB  - The C function gene AGAMOUS (AG) encodes for a MADS-box transcription factor
      required for floral organ identity and floral meristem (FM) determinacy in
      angiosperms. Unlike Arabidopsis, most legume plants possess two AG homologs arose
      by an ancient genome duplication event. Recently, two euAGAMOUS genes, MtAGa and
      MtAGb, were characterized and shown to fulfill the C function activity in the
      model legume Medicago truncatula. Here, we reported the isolation and
      characterization of a new mtaga allele by screening the Medicago Tnt1 insertion
      mutant collection. We found that MtAGa was not only required for controlling the
      stamen and carpel identity but also affected pod and seed development. Genetic
      analysis indicated that MtAGa and MtAGb redundantly control Medicago floral organ
      identity, but have minimal distinct functions in regulating stamen and carpel
      development in a dose-dependent manner. Interestingly, the stamens and carpels
      are mostly converted to numerous vexillum-like petals in the double mutant of
      mtaga mtagb, which is distinguished from Arabidopsis ag. Further qRT-PCR analysis
      in different mtag mutants revealed that MtAGa and MtAGb can repress the
      expression of putative A and B function genes as well as MtWUS, but promote
      putative D function genes expression in M. truncatula. In addition, we found that
      the abnormal dorsal petal phenotype observed in the mtaga mtagb double mutant is
      associated with the upregulation of CYCLOIDEA (CYC)-like TCP genes. Taken
      together, our data suggest that the redundant MtAGa and MtAGb genes of M.
      truncatula employ a conserved mechanism of action similar to Arabidopsis in
      determining floral organ identity and FM determinacy but may have evolved
      distinct function in regulating floral symmetry by coordinating with specific
      floral dorsoventral identity factors.

PMID- 30108598
TI  - Arabidopsis Serine Decarboxylase 1 (SDC1) in Phospholipid and Amino Acid
      Metabolism.
AB  - Arabidopsis thaliana serine decarboxylase 1 (SDC1) catalyzes conversion of serine
      to ethanolamine, the first reaction step of phosphatidylcholine and
      phosphatidylethanolamine biosynthesis. However, an involvement of SDC1 in amino
      acid metabolism remains elusive despite that serine is the substrate of SDC1.
      Here, we showed that SDC1 localizes in mitochondria although phosphatidylcholine
      and phosphatidylethanolamine are known to be produced in the endoplasmic
      reticulum (ER). Moreover, we found that overexpression of SDC1 decreased levels
      of amino acid compounds derived from mitochondrial tricarboxylic acid cycle.
      These results suggest that mitochondria-localized SDC1 plays an important role in
      both phospholipid and amino acid metabolism in A. thaliana.

PMID- 30108596
TI  - Posttranscriptional Gene Regulation of T Follicular Helper Cells by RNA-Binding
      Proteins and microRNAs.
AB  - T follicular helper (Tfh) cells are critically involved in the establishment of
      potent antibody responses against infectious pathogens, such as viruses and
      bacteria, but their dysregulation may also result in aberrant antibody responses
      that frequently coincide with autoimmune diseases or allergies. The fate and
      identity of Tfh cells is tightly controlled by gene regulation on the
      transcriptional and posttranscriptional level. Here, we provide deeper insights
      into the posttranscriptional mechanisms that regulate Tfh cell differentiation,
      function, and plasticity through the actions of RNA-binding proteins (RBPs) and
      small endogenously expressed regulatory RNAs called microRNAs (miRNAs). The
      Roquin family of RBPs has been shown to dampen spontaneous activation and
      differentiation of naive CD4+ T cells into Tfh cells, since CD4+ T cells with
      Roquin mutations accumulate as Tfh cells and provide inappropriate B cell help in
      the production of autoantibodies. Moreover, Regnase-1, an endoribonuclease that
      regulates a set of targets, which strongly overlaps with that of Roquin, is
      crucial for the prevention of autoantibody production. Interestingly, both Roquin
      and Regnase-1 proteins are cleaved and inactivated after TCR stimulation by the
      paracaspase MALT1. miRNAs are expressed in naive CD4+ T cells and help preventing
      spontaneous differentiation into effector cells. While most miRNAs are
      downregulated upon T cell activation, several miRNAs have been shown to regulate
      the fate of these cells by either promoting (e.g., miR-17-92 and miR-155) or
      inhibiting (e.g., miR-146a) Tfh cell differentiation. Together, these different
      aspects highlight a complex and dynamic regulatory network of posttranscriptional
      gene regulation in Tfh cells that may also be active in other T helper cell
      populations, including Th1, Th2, Th17, and Treg.

PMID- 30108599
TI  - Canopy and Ear Traits Associated With Avoidance of Fusarium Head Blight in Wheat.
AB  - Doubled haploid and elite wheat genotypes were ground inoculated in three field
      experiments and head spray inoculated in two glasshouse experiments, using mixed
      Fusarium and Microdochium species, to identify crop canopy and ear traits
      associated with Fusarium head blight (FHB) disease. In all experiments, flag leaf
      length and tiller number were consistently identified as the most significant
      canopy traits contributing to progression of FHB caused by Fusarium graminearum,
      F. culmorum, and F. avenaceum. The influence of ear traits was greater for F.
      poae that may possess more diverse routes for transmission and spread.
      Consistently, spikelet density was associated with increased disease severity in
      the field. F. graminearum, F. culmorum, and F. langsethiae were the main
      mycotoxin producers and their respective toxins were significantly related to
      fungal biomass and number of spikelets per ear. Genotypes with lower tiller
      numbers, shorter flag leaves and less dense ears may be able to avoid FHB disease
      caused by F. graminearum, F. culmorum, F. avenaceum, or Microdochium species
      however selection for these canopy and ear architectural traits to enable disease
      avoidance in wheat is likely to result in a potential trade-off with grain yield
      and therefore only moderately advantageous in susceptible genotypes.

PMID- 30108600
TI  - Integration of Genetic and Cytogenetic Maps and Identification of Sex Chromosome
      in Garden Asparagus (Asparagus officinalis L.).
AB  - A genetic linkage map of dioecious garden asparagus (Asparagus officinalis L., 2n
      = 2x = 20) was constructed using F1 population, simple sequence repeat (SSR) and
      single nucleotide polymorphism (SNP) markers. In total, 1376 SNPs and 27 SSRs
      were used for genetic mapping. Two resulting parental maps contained 907 and 678
      markers spanning 1947 and 1814 cM, for female and male parent, respectively, over
      ten linkage groups representing ten haploid chromosomes of the species. With the
      aim to anchor the ten genetic linkage groups to individual chromosomes and
      develop a tool to facilitate genome analysis and gene cloning, we have optimized
      a protocol for flow cytometric chromosome analysis and sorting in asparagus. The
      analysis of DAPI-stained suspensions of intact mitotic chromosomes by flow
      cytometry resulted in histograms of relative fluorescence intensity (flow
      karyotypes) comprising eight major peaks. The analysis of chromosome morphology
      and localization of 5S and 45S rDNA by FISH on flow-sorted chromosomes, revealed
      that four chromosomes (IV, V, VI, VIII) could be discriminated and sorted.
      Seventy-two SSR markers were used to characterize chromosome content of
      individual peaks on the flow karyotype. Out of them, 27 were included in the
      genetic linkage map and anchored genetic linkage groups to chromosomes. The sex
      determining locus was located on LG5, which was associated with peak V
      representing a chromosome with 5S rDNA locus. The results obtained in this study
      will support asparagus improvement by facilitating targeted marker development
      and gene isolation using flow-sorted chromosomes.

PMID- 30108601
TI  - Nocturnal Bee Pollinators Are Attracted to Guarana Flowers by Their Scents.
AB  - Floral scent is an important component of the trait repertoire of flowering
      plants, which is used to attract and manipulate pollinators. Despite advances
      during the last decades about the chemicals released by flowers, there is still a
      large gap in our understanding of chemical communication between flowering plants
      and their pollinators. We analyzed floral scents of guarana (Paullinia cupana,
      Sapindaceae), an economically important plant of the Amazon, using chemical
      analytical approaches, and determined the attractiveness of the scent to its
      nocturnal bee pollinators using behavioral assays in the field. Pollen loads of
      attracted bees were also analyzed. Inflorescences of guarana emit strong scents,
      both during day and at night, with some semi-quantitative differences between day
      and night-time scents. Synthetic scent mixtures containing some of the
      identified floral scent components, including the most abundant ones, i.e.,
      linalool and (E)-beta-ocimene, successfully attracted the nocturnal Megalopta bee
      pollinators. Pollen analyses revealed that many of the attracted bees had pollen
      grains from previous visits to guarana flowers on their bodies. Overall, our data
      show that guarana flowers attract nocturnal bee visitors by their strong scents
      and suggest that the chemical communication between this plant and its
      pollinators is a key component in crop production of this economically important
      plant species.

PMID- 30108603
TI  - Altitudinal Patterns of Leaf Traits and Leaf Allometry in Bamboo Pleioblastus
      amarus.
AB  - Awareness of local-scale variation in leaf traits for a single species and the
      relationships between these traits and their dependence on altitude might be
      essential for extrapolating ecophysiological processes from the leaf to the
      ecosystem level. While altitudinal patterns of leaf traits have been extensively
      studied in a number of species, little is known about such patterns in bamboos.
      We analyzed leaf functional traits and leaf allometric relationships of
      Pleioblastus amarus at three different altitudes (200, 400, and 800 m). With
      increasing altitude, most functional traits, including leaf length, width,
      perimeter, area, dry weight, and water content, decreased significantly, while
      the leaf length:width ratio exhibited a marked increase, resulting in a tendency
      toward narrow leaves. Specific leaf area first increased, and then decreased,
      while the change in leaf dry matter content showed the opposite trend. Leaf area
      was positively correlated with leaf length, leaf width and leaf perimeter, but
      negatively correlated with the leaf length:width ratio. With increasing altitude,
      the slopes of these relationships for leaf area first increased, and then
      decreased. Leaf biomass was positively correlated with leaf length, width,
      perimeter, and area, with the slopes of the relationships being the same at all
      altitudes. Thus, the leaves of this bamboo species at middle altitude have the
      highest specific leaf area and lowest leaf dry matter content. Our findings
      suggest that this bamboo species has a big potential of growth and morphological
      plasticity.

PMID- 30108602
TI  - The Functional Change and Deletion of FLC Homologs Contribute to the Evolution of
      Rapid Flowering in Boechera stricta.
AB  - Differences in the timing of vegetative-to-reproductive phase transition have
      evolved independently and repeatedly in different plant species. Due to their
      specific biological functions and positions in pathways, some genes are important
      targets of repeated evolution - independent mutations on these genes caused the
      evolution of similar phenotypes in distantly related organisms. While many
      studies have investigated these genes, it remains unclear how gene duplications
      influence repeated phenotypic evolution. Here we characterized the genetic
      architecture underlying a novel rapid-flowering phenotype in Boechera stricta and
      investigated the candidate genes BsFLC1 and BsFLC2. The expression patterns of
      BsFLC1 suggested its function in flowering time suppression, and the deletion of
      BsFLC1 is associated with rapid flowering and loss of vernalization requirement.
      In contrast, BsFLC2 did not appear to be associated with flowering and had
      accumulated multiple amino acid substitutions in the relatively short
      evolutionary timeframe after gene duplication. These non-synonymous substitutions
      greatly changed the physicochemical properties of the original amino acids,
      concentrated non-randomly near a protein-interacting domain, and had greater
      substitution rate than synonymous changes. Here we suggested that, after recent
      gene duplication of the FLC gene, the evolution of rapid phenology was made
      possible by the change of BsFLC2 expression pattern or protein sequences and the
      deletion of BsFLC1.

PMID- 30108604
TI  - Low Nitrogen Application Enhances Starch-Metabolizing Enzyme Activity and
      Improves Accumulation and Translocation of Non-structural Carbohydrates in Rice
      Stems.
AB  - More than 4 billion inhabitants in Asia depend on rice for 35-60% of the calories
      consumed in their diets, but new rice cultivars frequently do not reach expected
      yields because of poor rice grain filling. Here, we quantified the activities of
      enzymes involved in starch metabolization in rice to investigate the mechanisms
      regulating the accumulation and translocation of stem non-structural
      carbohydrates (NSC) under different levels of nitrogen fertilizer application. A
      pot experiment was conducted using two rice cultivars, Liangyoupeijiu (LYPJ) and
      Shanyou63 (SY63), under high and low nitrogen applications. Compared with high
      nitrogen application (HN), low nitrogen application (LN) increased stem NSC
      concentration before the heading stage and NSC translocation during the grain
      filling stage; concomitantly, LN significantly shortened the active grain filling
      period and increased the grain filling rate in superior spikelets. Compared with
      the LYPJ cultivar, SY63 exhibited a higher grain weight, higher grain filling
      percentage, and higher stem NSC concentration before heading and greater NSC
      translocation after heading. During the period between panicle initiation and
      heading, the activities of adenosine diphosphate-glucose pyrophosphorylase (AGP),
      starch synthase (StS), and starch branching enzyme (SBE), all enzymes involved in
      starch synthesis, increased under the LN treatment and positively correlated with
      increases in stem NSC. During grain filling, the activities of enzymes involved
      in starch-to-sucrose conversion [alpha-amylase, beta-amylase, and sucrose
      phosphate synthase (SPS)] increased under the LN treatment and positively
      correlated with stem NSC remobilization. Overall, the investigated enzymes
      exhibited higher activities in SY63 than in LYPJ. Our results suggest that low
      nitrogen increases the activities of AGP, StS, SBE, alpha-amylase, beta-amylase,
      and SPS, leading to increased accumulation and remobilization of stem starch and
      NSC in SY63. We conclude that calculated reductions in nitrogen application and
      the choice of an appropriate cultivar may improve rice grain yields via enhanced
      stem NSC accumulation and translocation, thereby reducing the costs and
      increasing the sustainability of rice production.

PMID- 30108605
TI  - Snowmelt Timing Regulates Community Composition, Phenology, and Physiological
      Performance of Alpine Plants.
AB  - The spatial patterning of alpine plant communities is strongly influenced by the
      variation in physical factors such as temperature and moisture, which are
      strongly affected by snow depth and snowmelt patterns. Earlier snowmelt timing
      and greater soil-moisture limitations may favor wide-ranging species adapted to a
      broader set of ecohydrological conditions than alpine-restricted species. We
      asked how plant community composition, phenology, plant water relations, and
      photosynthetic gas exchange of alpine-restricted and wide-ranging species differ
      in their responses to a ca. 40-day snowmelt gradient in the Colorado Rocky
      Mountains (Lewisia pygmaea, Sibbaldia procumbens, and Hymenoxys grandiflora were
      alpine-restricted and Artemisia scopulorum, Carex rupestris, and Geum rossii were
      wide-ranging species). As hypothesized, species richness and foliar cover
      increased with earlier snowmelt, due to a greater abundance of wide-ranging
      species present in earlier melting plots. Flowering initiation occurred earlier
      with earlier snowmelt for 12 out of 19 species analyzed, while flowering duration
      was shortened with later snowmelt for six species (all but one were wide-ranging
      species). We observed >50% declines in net photosynthesis from July to September
      as soil moisture and plant water potentials declined. Early-season stomatal
      conductance was higher in wide-ranging species, indicating a more competitive
      strategy for water acquisition when soil moisture is high. Even so, there were no
      associated differences in photosynthesis or transpiration, suggesting no strong
      differences between these groups in physiology. Our findings reveal that plant
      species with different ranges (alpine-restricted vs. wide-ranging) could have
      differential phenological and physiological responses to snowmelt timing and
      associated soil moisture dry-down, and that alpine-restricted species'
      performance is more sensitive to snowmelt. As a result, alpine-restricted species
      may serve as better indicator species than their wide-ranging heterospecifics.
      Overall, alpine community composition and peak % cover are strongly structured by
      spatio-temporal patterns in snowmelt timing. Thus, near-term, community-wide
      changes (or variation) in phenology and physiology in response to shifts in
      snowmelt timing or rates of soil dry down are likely to be contingent on the
      legacy of past climate on community structure.

PMID- 30108606
TI  - Prediction of Drug-Gene Interaction by Using Metapath2vec.
AB  - Heterogeneous information networks (HINs) currently play an important role in
      daily life. HINs are applied in many fields, such as science research, e
      commerce, recommendation systems, and bioinformatics. Particularly, HINs have
      been used in biomedical research. Algorithms have been proposed to calculate the
      correlations between drugs and targets and between diseases and genes. Recently,
      the interaction between drugs and human genes has become an important subject in
      the research on drug efficacy and human genomics. In previous studies, numerous
      prediction methods using machine learning and statistical prediction models were
      proposed to explore this interaction on the biological network. In the current
      work, we introduce a representation learning method into the biological
      heterogeneous network and use the representation learning models metapath2vec and
      metapath2vec++ on our dataset. We combine the adverse drug reaction (ADR) data in
      the drug-gene network with causal relationship between drugs and ADRs. This
      article first presents an analysis of the importance of predicting drug-gene
      relationships and discusses the existing prediction methods. Second, the skip
      gram model commonly used in representation learning for natural language
      processing tasks is explained. Third, the metapath2vec and metapath2vec++ models
      for the example of drug-gene-ADR network are described. Next, the kernelized
      Bayesian matrix factorization algorithm is used to complete the prediction.
      Finally, the experimental results of both models are compared with Katz,
      CATAPULT, and matrix factorization, the prediction visualized using the receiver
      operating characteristic curves are presented, and the area under the receiver
      operating characteristic values for three varying algorithm parameters are
      calculated.

PMID- 30108608
TI  - Zearalenone Exposure Enhanced the Expression of Tumorigenesis Genes in Donkey
      Granulosa Cells via the PTEN/PI3K/AKT Signaling Pathway.
AB  - Zearalenone (ZEA) is a natural contaminant existing in food and feed products
      that exhibits a negative effect on domestic animals' reproduction. Donkeys
      possess high economic value in China and are at risk of exposure to ZEA. However,
      few information is available on ZEA-induced toxicity and no report on toxicity in
      donkeys can be found in scientific literature. We investigated the biological
      effects of ZEA exposure on donkey granulosa cells (dGCs) by using RNA-seq
      analysis. ZEA at 10 and 30 MUM were administered to GCs within 72 h of in vitro
      culture. ZEA at 10 MUM significantly altered the tumorigenesis associated genes
      in dGCs. Exposure to 10 and 30 MUM ZEA treatment significantly reduced mRNA
      expression of PTEN, TGFbeta, ATM, and CDK2 genes, particularly, the ZEA treatment
      significantly increased the expression of PI3K and AKT genes. Furthermore,
      immunofluorescence, RT-qPCR, and Western blot analysis verified the gene
      expression of ZEA-exposed GCs. Collectively, these results demonstrated the
      deleterious effect of ZEA exposure on the induction of ovarian cancer related
      genes via the PTEN/PI3K/AKT signaling pathway in dGCs in vitro.

PMID- 30108609
TI  - Early mortality and safety after transcatheter aortic valve replacement using the
      SAPIEN 3 in nonagenarians.
AB  - Background: Transcatheter aortic valve replacement (TAVR) has been performed for
      many elderly patients with severe aortic stenosis (AS). The SAPIEN 3 is one of
      the latest balloon-expandable prosthesis. This study aimed to investigate the
      early clinical outcomes after TAVR using the SAPIEN 3 in nonagenarians. Methods:
      A total of 97 consecutive patients underwent TAVR for severe AS between December
      2015 and December 2016. Of these, 85 consecutive patients who underwent TAVR
      using the SAPIEN 3 were included. According to the age, patients were classified
      into age >= 90 years group (17 patients) or age < 90 years group (68 patients).
      The clinical outcomes including all-cause mortality and composite endpoint of
      early safety at 30 days were evaluated. Results: The Society of Thoracic Surgeons
      score in age >= 90 years group was higher than age < 90 years group (12.3 +/-
      6.1% vs. 8.5 +/- 5.1%, P < 0.01). There was no significant difference in 30-day
      mortality between the two groups. However, the life-threatening bleeding and
      major vascular complications in age >= 90 years group were greater than age < 90
      years group (11.8% vs. 1.5%, P = 0.04 and 11.8% vs. 1.5%, P = 0.04,
      respectively). The composite endpoint of early safety at 30 days was similar
      between the two groups. Multivariate logistic regression analysis showed that
      prior myocardial infarction was an independent predictor of the composite
      endpoint of early safety (odds ratio: 4.76, 95% confidence interval: 1.02-22.21,
      P = 0.047). Conclusions: The early mortality and safety after TAVR using the
      SAPIEN 3 in nonagenarians were similar and acceptable despite of higher operative
      risk.

PMID- 30108607
TI  - COMT Val158Met Polymorphism and Social Impairment Interactively Affect Attention
      Deficit Hyperactivity Symptoms in Healthy Adolescents.
AB  - The dopaminergic system has been shown to have substantial effects on the
      etiology of attention-deficit hyperactivity disorder (ADHD). However, while some
      studies found a significant direct effect, others did not. In this context,
      social behavior might play an important role as a factor that is related both to
      the dopaminergic system and ADHD. In a large epidemiological sample of
      adolescents (N = 462; 16-17 years), we assessed the level of ADHD symptoms using
      the Strengths and Difficulties Questionnaire, social behavior using the Social
      Responsiveness Scale, and the allelic distribution of the dopaminergic catechol-O
      methyltransferase (COMT) Val158Met polymorphism. We found a significant
      association between COMT and social impairment, insofar as Met-allele carriers
      showed increased levels of social impairment. Moreover, social impairment
      significantly determined an association between COMT and ADHD (explained
      variance: 19.09%). This effect did not significantly differ between males and
      females. COMT and social impairment might interactively affect ADHD
      symptomatology, and could thus represent significant gene-phenotypic risk factors
      for ADHD symptomatology. This might have interesting implications for prevention
      and intervention strategies with a focus on social behavior in genetically at
      risk individuals.

PMID- 30108610
TI  - Impact of gender on outcomes after transcatheter aortic valve implantation.
AB  - Backgound: The influence of gender on clinical outcomes following transcatheter
      aortic valve implantation (TAVI) was considerably discrepant in previous studies.
      We aimed to investigate the impact of gender in our registry. Methods: The study
      is a retrospective observational analysis of a prospectively designed cohort (546
      consecutive patients treated at the University Hospital Zurich who were enrolled
      in Swiss TAVI Cohort from May 2008 to April 2014). The Study took place in
      University Heart Centre at University Hospital Zurich, Switzerland. Results: Both
      genders were equally represented with 51.5 % (n = 281) of the populations being
      females, who were significantly older and had a more pronounced history of
      hypertension (P < 0.001). Males on the other hand showed a higher incidence of
      diabetes (P = 0.004), coronary artery disease (P < 0.001), chronic obstructive
      pulmonary disease (P < 0.001) and renal failure requiring renal replacement
      therapy (P = 0.018). Patients were followed up for a median of 391 days with a
      100% complete follow-up at one year. The primary outcome (all-cause mortality)
      occurred in 6.8% (n = 37) and 15% (n = 82) of patients at 30 days and one year,
      respectively. The 30-day all-cause mortality outcome did not significantly differ
      between females (7.5%) and males (6.0%) (P = 0.619), but one year all-cause
      mortality occurred significantly more in males than in females (18.7% vs. 11.7%,
      P < 0.037). Conclusion: After TAVI implantation for severe aortic stenosis, males
      have a less favorable long-term (one year) mortality outcome than females.

PMID- 30108611
TI  - Low dose oral haloperidol does not prolong QTc interval in older acutely
      hospitalised adults: a subanalysis of a randomised double-blind placebo
      controlled study.
AB  - Background: Haloperidol is the most frequently prescribed antipsychotic for
      delirium symptoms. The risk of QTc prolongation often raises concerns, although
      the effect of haloperidol on QTc interval has not yet been investigated in a
      randomised placebo-controlled fixed-dose study. Methods: A subanalysis of a
      randomised double-blind placebo-controlled study was conducted to evaluate the
      effect of prophylactic haloperidol 1 mg or placebo 1 mg orally twice-daily
      (maximum of 14 doses) on QTc interval in patients aged 70 years and over.
      Bedside, 12-lead ECGs were recorded before, during and after the one-week
      intervention period. Automatic QTc measurements were obtained in addition to
      manual measurements of QT and RR intervals, blinded for treatment status. Manual
      measurements were corrected (QTc) using Bazett (QTc-B), Framingham (QTc-Fa),
      Fridericia (QTc-Fi) and Hodges (QTc-H) methods. Mixed model analyses were used to
      test for differences in longitudinal course of QTc between patients receiving
      haloperidol and placebo. Results: ECG recordings of 72 patients (haloperidol n =
      38) were analysed, 45.8% male. Median (range) haloperidol serum concentration on
      day 4 was 0.71 (0.32-1.82) ug/L (n = 23). Longitudinal course of mean QTc did not
      significantly differ between treatment arms for any of the automatic or manually
      derived QTc values. Conclusions: Low dose oral haloperidol did not result in QTc
      prolongation in older acutely hospitalised patients. Results may not be
      generalizable to patients with existing ECG abnormalities such as atrial
      fibrillation.

PMID- 30108612
TI  - Predictive value of red cell distribution width on left atrial thrombus or left
      atrial spontaneous echo contrast in patients with non-valvular atrial
      fibrillation.
AB  - Objective: To evaluate the predictive value of red cell distribution width (RDW)
      on left atrial thrombus (LAT) or left atrial spontaneous echo contrast (LASEC) in
      patients with non-valvular atrial fibrillation (AF). Methods: We reviewed 692
      patients who were diagnosed as non-valvular AF and underwent transesophageal
      echocardiography (TEE) in Guangdong Cardiovascular Institute from April 2014 to
      December 2015. The baseline clinical characteristics, laboratory test of blood
      routine, electrocardiograph measurements were analyzed. Results: Eighty-four
      patients were examined with LAT/LASEC under TEE. The mean RDW level was
      significantly higher in LAT/LASEC patients compared with the non-LAT/LASEC
      patients (13.59% +/- 1.07% vs. 14.34% +/- 1.34%; P < 0.001). Receiver-operating
      characteristic curve analysis was performed and indicated the best RDW cut point
      was 13.16%. Furthermore, multivariate logistic regression analysis indicated that
      RDW level > 13.16% could be an independent risk factor for LAT/LASEC in patients
      with AF. Conclusion: Elevated RDW level is associated with the presence of
      LAT/LASEC and could be with moderate predictive value for LAT/LASEC in patients
      with non-valvular AF.

PMID- 30108613
TI  - Influenza vaccination in acute coronary syndromes patients in Thailand: the cost
      effectiveness analysis of the prevention for cardiovascular events and pneumonia.
AB  - Background: Influenza vaccination has been clinically shown to reduce adverse
      cardiovascular outcomes in acute coronary syndrome (ACS) patients, but the
      economic perspectives can provide important data to make informed decisions. This
      study aimed to perform the economic evaluation of lifelong annual influenza
      vaccination for cardiovascular events and well-established pneumonia prevention.
      Methods: Lifetime costs, life-expectancy, and quality-adjusted live years (QALYs)
      were estimated beyond one-year cycle length of a six-health states Markov model
      condition on whether a hospitalization for ACS, stroke, heart failure, pneumonia,
      no hospitalizations occurred, or death. The comparison of three age-groups of 40
      49, 50-65, and > 65 years scenario was performed. Incremental cost-effectiveness
      ratio (ICER) and net monetary benefit (NMB) were presented as a societal
      perspective in 2016. The model robustness was determined by one-way and
      probabilistic sensitivity analyses. Results: The influenza vaccination was cost
      effective in all age-groups, by dominant ICERs (lower cost with higher
      effectiveness) which was completely lower than acceptable willingness-to-pay
      threshold of Thailand [160,000 THB (4,466.8 USD) per QALYs], with a great
      incremental value of NMB. Especially, the 50-year-old-and-above scenario was
      shown as the most benefit at 129,092 THB (3,603.9 USD) for each patient.
      Conclusions: The annually additional influenza vaccination to standard treatment
      in ACS was cost-effective in all age-groups, which should be considered in
      clinical practice and health-policy making process.

PMID- 30108614
TI  - Obesity, metabolic abnormalities, and mortality in older men.
AB  - Background: Older adults are prone to obesity and metabolic abnormalities and
      recommended to pursue a normal weight especially when obesity and metabolic
      abnormalities are co-existed. However, few studies have reported the possible
      differences in the effect of obesity on outcomes between older adults with
      metabolic abnormalities and those without metabolic abnormalities. Methods: A
      total of 3485 older men were included from 2000 to 2014. All-cause mortality and
      cardiovascular mortality were obtained during a mean follow-up of five years.
      Metabolic abnormalities were defined as having established hypertension,
      diabetes, or dyslipidemia and taking the disease-related medications. All
      participants were stratified by the presence or absence of metabolic
      abnormalities. Results: In the non-metabolic abnormalities group, all-cause and
      cardiovascular deaths were lowest in overweight participants and highest in obese
      participants. In the metabolic abnormalities group, mortality was also lowest in
      overweight participants but highest in participants with normal weight. After
      adjustment for covariates, hazard ratios (95% CI) for all-cause death and
      cardiovascular death were 0.68 (0.51, 0.92) and 0.59 (0.37, 0.93), respectively,
      in overweight participants with metabolic abnormalities. Furthermore, obesity was
      not associated with mortality risk in both groups. These findings were unchanged
      in stratified analyses. Conclusions: Overweight was negatively associated with
      mortality risk in older men with metabolic abnormalities but not in those without
      metabolic abnormalities. Obesity did not increase death risk regardless of
      metabolic abnormalities. These findings suggest that the recommendation of
      pursuing a normal weight may be wrong in overweight/obese older men, especially
      for those with metabolic abnormalities.

PMID- 30108615
TI  - Clinical features and treatment options for mitral regurgitation in elderly
      inpatients.
AB  - Objective: To summarize clinical characteristics and treatment strategy of
      Chinese elderly mitral regurgitation (MR) inpatients under the current
      guidelines, and to identify factors related to treatment options in them.
      Methods: A single center retrospective study was conducted in which patients
      hospitalized in Fuwai hospital from May 1st of 2014 to April 30 of 2015 with
      moderate to severe MR assessed by transthoracic echocardiography were enrolled
      consecutively (n = 1741). Patients > 60 years old were grouped as elderly group
      (n = 680) and patients < 60 years were grouped as control group (n = 1061). The
      elderly group was categorized into two subgroups based on surgical status.
      Result: s The mean age of the elderly group was 66.98 +/- 5.94 years. The most
      common reason of MR in elderly group was degenerative MR (41.18%).
      Atherosclerotic risk factors such as hypertension, diabetes or hyperlipidaemia
      were more commonly observed in elderly group than the control group (45.44% vs.
      25.17%, P < 0.001; 19.56% vs. 8.48%, P < 0.001; 35.29% vs. 19.51%, P < 0.001).
      Elderly group had higher EuroscoreIIscore (5.54 +/- 2.42 vs. 3.15 +/- 1.66),
      greater left ventricular end diastolic diameter (LVEDD) (57.72 +/- 12.3 vs. 57.33
      +/- 10.19 mm) and a lower surgery rate (54.71% vs. 63.91%); P < 0.05. Age, left
      ventricular ejection fraction (LVEF), regurgitation grade, EuroScore-II high risk
      stratification and having diabetes were identified as factors associated with
      therapy decisions in elderly MR patients. Conclusions: Valve surgery was denied
      in 45.29% of elderly MR inpatients. Older age, impaired LVEF, lower regurgitation
      grade, EuroScore-II high risk stratification, and having diabetes were factors
      most significantly associated with surgery denial among elderly Chinese
      inpatients with MR.

PMID- 30108616
TI  - Genetically confirmed familial hypercholesterolemia in outpatients with
      hypercholesterolemia.
AB  - Background: Familial hypercholesterolemia (FH) is an autosomal dominant disorder
      of lipoprotein metabolism which can lead to premature coronary heart disease
      (pCHD). There are about 3.8 million potential FH patients in China, whereas the
      clinical and genetic data of FH are limited. Methods: Dutch Lipid Clinic Network
      (DLCN) criteria was used to diagnose FH in outpatients with hypercholesterolemia.
      Resequencing chip analysis combined with Sanger sequencing validation were used
      to identify mutations in the definite FH patients according to DLCN criteria. In
      silico analysis was conducted in mutations with previously unknown pathogenicity.
      Then, the novel mutant receptors were transfected into human embryo kidney 293
      (HEK-293) cells. The binding and the internalization activities of the mutant
      receptors were analyzed by flow cytometry. Results: The prevalence of definite FH
      in outpatients with hypercholesterolemia in this study is 3.2%. Using genetic
      testing, one homozygous FH (HoFH), one heterozygous FH (HeFH) and three compound
      heterozygous FH patients were confirmed. Eight mutations in low-density
      lipoprotein receptor (LDLR) gene were identified, in which c.357delG was a novel
      mutation and co-segregated with the FH phenotype. Bioinformatic analysis
      confirmed that c.357delG was a pathogenic mutation. Furthermore, when compared
      with the wild-type LDLRs by flow cytometry analysis, the binding and
      internalization activities of c.357delG mutant LDLRs were reduced by 35% and 49%,
      respectively. Conclusions: This study identified eight LDLR gene mutations in
      five patients with definite FH, in which c.357delG is a novel pathogenic
      mutation. These findings increase our understanding of the genetic spectrum of FH
      in China.

PMID- 30108617
TI  - The trend of change in catheter ablation versus antiarrhythmic drugs for the
      management of atrial fibrillation over time: a meta-analysis and meta-regression.
AB  - Objective: To evaluate the trend of change in the efficacy and safety of catheter
      ablation compared with antiarrhythmic drug therapy (ADT) for rhythm control in
      patients with atrial fibrillation (AF) over time. Methods: The online databases
      PubMed and EMBASE were searched for relevant studies. STATA software (version
      12.0) was used to perform the meta-analysis and meta-regression. Results: Fifteen
      randomized controlled trials including 2249 patients with AF were identified. The
      pooled results showed that catheter ablation was associated with a 52% reduction
      in the risk of AF recurrence compared with ADT [risk ratio (RR) = 0.48, 95%
      confidence interval (CI): 0.40-0.57, I2 = 70.7%). Subgroup analyses showed that
      catheter ablation exhibited less efficacy in studies after 2011 compared to
      studies before 2011 (RR = 0.61, 95% CI: 0.54-0.68, I2 = 9.3% and RR = 0.34, 95%
      CI: 0.24-0.47, I2 = 69.9%, respectively), and the safety outcome showed a 1.08
      fold higher incidence of adverse events (14.2% vs. 7.3%; RR = 1.08, 95% CI: 1.04
      1.13) in studies after 2011. Conclusions: Catheter ablation appears to be
      superior to ADT for rhythm control. However, less efficacy and a higher rate of
      adverse events were observed in studies after 2011 compared to studies before
      2011.

PMID- 30108619
TI  - CIED implantation in elderly patients: a single-center experience.

PMID- 30108618
TI  - Depression and chronic heart failure in the elderly: an intriguing relationship.
AB  - Chronic heart failure and depressive disorders have a high prevalence and
      incidence in the elderly. Several studies have shown how depression tends to
      exacerbate coexisting chronic heart failure and its clinical outcomes and vice
      versa, especially in the elderly. The negative synergism between chronic heart
      failure and depression in the elderly may be approached only taking into account
      the multifaceted pathophysiological characteristics underlying both these
      conditions, such as behavioural factors, neurohormonal activation, inflammatory
      mediators, hypercoagulability and vascular damage. Nevertheless, the
      pathophysiological link between these two conditions is not well established yet.
      Despite the high prevalence of depression in chronic heart failure elderly
      patients and its negative prognostic value, it is often unrecognized especially
      because of shared symptoms. So the screening of mood disorders, using reliable
      questionnaires, is recommended in elderly patients with chronic heart failure,
      even if cannot substitute a diagnostic interview by mental health professionals.
      In this setting, treatment of depression requires a multidisciplinary approach
      including: psychotherapy, antidepressants, exercise training and
      electroconvulsive therapy. Pharmacological therapy with selective serotonin
      reuptake inhibitors, despite conflicting results, improves quality of life but
      does not guarantee better outcomes. Exercise training is effective in improving
      quality of life and prognosis but at the same time cardiac rehabilitation
      services are vastly underutilized.

PMID- 30108620
TI  - Use of the reported Edmonton frail scale in the assessment of patients for
      transcatheter aortic valve replacement: a possible selection tool in very high
      risk patients?

PMID- 30108621
TI  - "Malignant" right coronary artery presenting as an ST-segment elevation
      myocardial infarction-a case report.

PMID- 30108623
TI  - Cane toads beneath bird rookeries: utilization of a natural disturbance by an
      invasive species.
AB  - Many invasive species exploit anthropogenically disturbed habitats, but most of
      those taxa evolved long before humans. Presumably, then, an ability to use
      natural (non-anthropogenic) disturbances pre-adapted invaders to a world later
      degraded by people. Studies on invasive species in naturally disturbed habitats
      thus can clarify the ancestral niche of invaders. In the Australian tropics,
      metallic starlings Aplonis metallica nest communally in emergent rainforest trees
      during the wet-season, and invasive cane toads Rhinella marina join other
      predators (mammals, birds, reptiles, and other anurans) to exploit the food
      resources beneath those trees. Compared to conspecifics found along nearby roads
      through the forest, cane toads beneath bird-nesting trees occur at higher
      densities, and are smaller in body size. The sex ratio is female-biased, and
      recapture records suggest that females may be philopatric at these sites (whereas
      recaptures were rare for both sexes found along the roads). Some toads were found
      under the same trees in successive wet-seasons. Spooling showed that distances
      moved per night were similar along the road versus under the trees, but toads
      under trees showed lower net displacements. Diets also differed (based upon scat
      analysis), with tree toads feeding more on beetles and less on ants. These
      nutrient-rich hotspots are exploited primarily by adult females and juvenile
      toads, whereas adult males congregate at breeding sites. By magnifying pre
      existing intraspecific divergences in habitat use, bird rookeries may enhance
      population viability of cane toads by enabling critical age and sex classes to
      exploit food-rich patches that are rarely used by adult males.

PMID- 30108622
TI  - Foraging, feeding, and physiological stress responses of wild wood mice to
      increased illumination and common genet cues.
AB  - In nature, animals are exposed to a broad range of threats imposed by predators,
      which may strongly influence the ecology of prey species directly or indirectly
      by affecting their behavior via fear of predation. Here, we studied wood mice
      Apodemus sylvaticus behavioral and physiological responses to simulated predation
      risk. Risk avoidance was analyzed by live trapping with control traps and traps
      treated with feces of common genet Genetta genetta (direct cue of risk) under new
      moon nights and following by simulated full moon conditions (indirect cue). The
      time devoted to foraging behavior and capture time were analyzed by video
      recording mice activity around traps. Food intake was calculated based on the
      amount of bait remaining in each trap. Fecal corticosterone metabolites (FCMs)
      were measured by enzyme-immunoassay as indicators of physiological stress
      responses. Fewer wood mice were captured during full moon, yet only non-breeding
      adult males clearly avoided common genet odor. Mice were captured sooner at night
      during the simulated full moon conditions and later in predator-treated traps.
      Foraging activity was lower when individuals faced predator's feces, but neither
      food intake nor FCM levels were affected by predation risk cues. Direct and
      indirect cues of predation risk selectively affected wood mice behavior, although
      behavioral responses seem to be modulated by different costs-benefit balances
      related to the individual's perception of risk. The lack of physiological
      responses to predation risk cues suggests that wood mice did not perceive them as
      reliable stressors or the response was too small or transient to be measured by
      FCM.

PMID- 30108624
TI  - Kinship promotes affiliative behaviors in a monkey.
AB  - In social mammals, kinship is an important factor that often affects the
      interactions among individuals within groups. In primates that live in a
      multilevel society, kinship may affect affiliative patterns between individuals
      at different scales within the larger group. For this study, we use field
      observations and molecular methods to reveal the profiles of how kinship affects
      affiliative behaviors between individuals in a breeding band of wild golden snub
      nosed monkeys (Rhinopithecus roxellana). We use a novel nonparametric test, the
      partition Mantel test, to measure independently the correlation between kinship
      and each of three affiliative behaviors. Our results show that more closely
      related females are more likely to groom each other. Average relatedness between
      adult females within the same one-male unit (OMU) is higher than that between
      adult females from different OMUs. We suggest that closely related females may
      reside in the same OMU in order to attain inclusive fitness benefits, and that
      kinship plays an important role in maintaining the social structure of this
      species.

PMID- 30108625
TI  - Morph-specific assortative mating in common wall lizard females.
AB  - Color polymorphism often is associated with alternative reproductive strategies
      and may reflect different adaptive optima that coexist within populations. The
      equilibrium among morph frequencies is maintained by the occurrence of opposite
      selective pressures (disruptive vs. stabilizing), which promote polymorphism
      while preserving gene flow. Sexual selection may contribute on both sides,
      particularly when morphs do not mate randomly. Reptiles offer a good model,
      notably lizards. Nevertheless, previous studies on mate choice in polymorphic
      lizards have generated contrasting results, with some studies suggesting that
      female morphs might tune their preference depending on environmental/social
      conditions such as crowding. We experimentally manipulated the number of
      individuals a female common wall lizard Podarcis muralis perceives around her, to
      test if females of different morphs (white or yellow) tune their choice for white
      and yellow males in order to maximize the probability that hatchlings follow the
      strategy best adapted to the population density. Results showed that crowding
      experienced by females did not affect mate choice, arguing against a flexible
      choice strategy by females. However, white females significantly associated with
      white males, whereas yellow females did not significantly associate with yellow
      males. Thus, sexual selection could contribute to the maintenance of color
      polymorphism in this species by a mix of assortative and non-assortative mating
      strategies, which could maintain the equilibrium between gene divergence and gene
      flow among morphs.

PMID- 30108626
TI  - Elevational divergence in the great tit complex revealed by major hemoglobin
      genes.
AB  - Gene flow and demographic history can play important roles in the adaptive
      genetic differentiation of species, which is rarely understood in the high
      altitude adaptive evolution of birds. To elucidate genetic divergence of
      populations in the great tit complex (Parus major, P. minor and P. cinereus) at
      different elevations, we compared the genetic structure and gene flow in
      hemoglobin genes with neutral loci. Our results revealed the elevationally
      divergent structure of alpha A -globin gene, distinctive from that of the beta A 
      globin gene and neutral loci. We further investigated gene flow patterns among
      the populations in the central-northern (> 1,000 m a.s.l.), south-eastern (<
      1,000 m a.s.l.) regions and the Southwest Mountains (> 2,000 m a.s.l.) in China.
      The high-altitude (> 1,000 m a.s.l.) diverged alpha A -globin genetic structure
      coincided with higher alpha A -globin gene flow between highland populations, in
      contrast to restricted neutral gene flow concordant with the phylogeny. The
      higher alpha A -globin gene flow suggests the possibility of adaptive evolution
      during population divergence, contrary to the lower alpha A -globin gene flow
      homogenized by neutral loci during population expansion. In concordance with
      patterns of historical gene flow, genotypic and allelic profiles provide
      distinctive patterns of fixation in different high-altitude populations. The
      fixation of alleles at contrasting elevations may primarily due to highland
      standing variants alpha A 49Asn/72Asn/108Ala originating from the south-western
      population. Our findings demonstrate a pattern of genetic divergence with gene
      flow in major hemoglobin genes depending on population demographic history.

PMID- 30108627
TI  - A perspective on sensory drive.

PMID- 30108629
TI  - Evaluation and hedonic value in mate choice.
AB  - Mating preferences can show extreme variation within and among individuals even
      when sensory inputs are conserved. This variation is a result of changes
      associated with evaluative mechanisms that assign positive, neutral, or negative
      hedonic value to stimuli-that is, label them as attractive, uninteresting, or
      unattractive. There is widespread behavioral evidence for differences in genes,
      environmental cues, or social experience leading to marked changes in the hedonic
      value of stimuli. Evaluation is accomplished through an array of mechanisms that
      are readily modifiable through genetic changes or environmental inputs, and that
      may often result in the rapid acquisition or loss of behavioral preferences.
      Reversals in preference arising from "flips" in hedonic value may be quite
      common. Incorporating such discontinuous changes into models of preference
      evolution may illuminate our understanding of processes like trait
      diversification, sexual conflict, and sympatric speciation.

PMID- 30108630
TI  - Visual "playback" of colorful signals in the field supports sensory drive for
      signal detectability.
AB  - Colorful visual signals are important systems for investigating the effects of
      signaling environments and receiver physiology on signal evolution as predicted
      by the sensory drive hypothesis. Support for the sensory drive hypothesis on
      color signal evolution is mostly based on documenting correlations between the
      properties of signals and habitat conditions under which the signals are given
      (i.e., a correlational approach) and less commonly on the use of mathematical
      models that integrate representations of visual environments, signal properties,
      and sensory systems (i.e., a functional approach). Here, we used an experimental
      approach in the field to evaluate signal efficacy of colorful lizard throat fans
      called dewlaps that show geographic variation in the lizard Anolis cristatellus.
      We used a remote controlled apparatus to display "fake dewlaps" to wild lizards
      to test for adaptive divergence in dewlap brightness (i.e., perceived intensity)
      among populations in situ. We found evidence of local adaptation in dewlap
      brightness consistent with the sensory drive hypothesis. Specifically, dewlaps
      that had the brightness characteristics of local lizards were more likely to be
      detected than those with the brightness characteristics of non-local lizards. Our
      findings indicate that simplified mathematical representations of visual
      environments may allow robust estimates of relative detectability or
      conspicuousness in natural habitats. We have shown the feasibility of evaluating
      color signal efficacy experimentally under natural conditions and demonstrate the
      potential advantages of presenting isolated components of signals to an intended
      receiver to measure their contribution to signal function.

PMID- 30108628
TI  - 25 Years of sensory drive: the evidence and its watery bias.
AB  - It has been 25 years since the formalization of the Sensory Drive hypothesis was
      published in the American Naturalist (1992). Since then, there has been an
      explosion of research identifying its utility in contributing to our
      understanding of inter- and intra-specific variation in sensory systems and
      signaling properties. The main tenet of Sensory Drive is that environmental
      characteristics will influence the evolutionary trajectory of both sensory
      (detecting capabilities) and signaling (detectable features and behaviors) traits
      in predictable directions. We review the accumulating evidence in 154 studies
      addressing these questions and categorized their approach in terms of testing for
      environmental influence on sensory tuning, signal characteristics, or both. For
      the subset of studies that examined sensory tuning, there was greater support for
      Sensory Drive processes shaping visual than auditory tuning, and it was more
      prevalent in aquatic than terrestrial habitats. Terrestrial habitats and visual
      traits were the prevalent habitat and sensory modality in the 104 studies showing
      support for environmental influence on signaling properties. An additional 19
      studies that found no supporting evidence for environmental influence on
      signaling traits were all based in terrestrial ecosystems and almost exclusively
      involved auditory signals. Only 29 studies examined the complete coevolutionary
      process between sensory and signaling traits and were dominated by fish visual
      communication. We discuss biophysical factors that may contribute to the visual
      and aquatic bias for Sensory Drive evidence, as well as biotic factors that may
      contribute to the lack of Sensory Drive processes in terrestrial acoustic
      signaling systems.

PMID- 30108632
TI  - A different view: sensory drive in the polarized-light realm.
AB  - Sensory drive, the concept that sensory systems primarily evolve under the
      influence of environmental features and that animal signals are evolutionarily
      shaped and tuned by these previously existing sensory systems, has been
      thoroughly studied regarding visual signals across many animals. Much of this
      work has focused on spectral aspects of vision and signals. Here, I review work
      on polarized-light signals of animals and relate these to what is known of
      polarization visual systems, polarized-light aspects of visual scenes, and
      polarization-related behavior (e.g., orientation, habitat-finding, contrast
      enhancement). Other than the broad patterns of scattered polarized light in the
      sky, most polarization in both terrestrial and aquatic environments results from
      either reflection or scattering in the horizontal plane. With overhead
      illumination, horizontal features such as the surfaces of many leaves or of air:
      water interfaces reflect horizontal polarization, and water scatters horizontally
      polarized light under most conditions. Several animal species have been
      demonstrated to use horizontally polarized light fields or features in critical
      aspects of their biology. Significantly, most biological signals are also
      horizontally polarized. Here, I present relevant polarization-related behavior
      and discuss the hypothesis that sensory drive has evolutionarily influenced the
      structure of polarization signals. The paper also considers the evolutionary
      origin of circular polarization vision and circularly polarized signals. It
      appears that this class of signals did not evolve under the influence of sensory
      drive. The study of signals based on polarized light is becoming a mature field
      of research.

PMID- 30108631
TI  - The pervasive effects of lighting environments on sensory drive in bluefin
      killifish: an investigation into male/male competition, female choice, and
      predation.
AB  - Sensory drive predicts that the conditions under which signaling takes place have
      large effects on signals, sensory systems, and behavior. The coupling of an
      ecological genetics approach with sensory drive has been fruitful. An ecological
      genetics approach compares populations that experience different environments and
      asks whether population differences are adaptive and are the result of genetic
      and/or environmental variation. The multi-faceted effects of signaling
      environments are well-exemplified by the bluefin killifish. In this system, males
      with blue anal fins are abundant in tannin-stained swamps that lack UV/blue light
      but are absent in clear springs where UV/blue light is abundant. Past work
      indicates that lighting environments shape genetic and environmental variation in
      color patterns, visual systems, and behavior. Less is known about the selective
      forces creating the across population correlations between UV/blue light and the
      abundance of blue males. Here, we present three new experiments that investigate
      the roles of lighting environments on male competition, female mate choice, and
      predation. We found strong effects of lighting environments on male competition
      where blue males were more likely to emerge as dominant in tea-stained water than
      in clear water. Our preliminary study on predation indicated that blue males may
      be less susceptible to predation in tea-stained water than in clear water.
      However, there was little evidence for female preferences favoring blue males.
      The resulting pattern is one where the effects of lighting environments on
      genetic variation and phenotypic plasticity match the direction of selection and
      favor the expression of blue males in swamps.

PMID- 30108635
TI  - The effect of different digoxin concentrations on heart tissue and antioxidant
      status in iron-overloaded rats.
AB  - BACKGROUND: Thalassaemia is a hereditary disorder and has an economic burden on
      patients and the government. The most prevalent complication in these patients is
      iron overload which is followed by cardiomyopathy. Digoxin is considered as a
      treatment against heart failure in thalassaemia. The present study evaluated the
      effect of two digoxin concentrations on iron content and antioxidative defense in
      cardiac tissue of iron-overloaded rats. METHODS: The study was conducted on 48
      rats which were divided into 6 groups. Group 1 was the control group and did not
      receive any treatment and group 2 was the iron overload group. In addition groups
      3 and 4 were the digoxin control groups which received 1 and 5 mg/kg/day of
      digoxin, respectively. Groups 5 and 6 received 1 and 5 mg/kg/day of digoxin plus
      iron-dextran, respectively. After 1 month, malondialdehyde (MDA), superoxide
      dismutase (SOD), glutathione peroxidase (GPX), and total antioxidant status (TAS)
      were assessed in cardiac tissues. RESULTS: Co-administration of iron-dextran and
      digoxin (1 and 5 mg/kg/day) significantly increased SOD and TAS levels (P <
      0.0010) and reduced MDA (P < 0.0010) in heart tissue compared to control and iron
      overload groups. GPX levels significantly reduced in groups 5 and 6 (iron +
      digoxin 1 (P < 0.0500) and iron + digoxin 5) (P < 0.0010) compared to the iron
      control group. CONCLUSION: Digoxin remarkably facilitates iron uptake by
      cardiomyocytes by affecting other channels such as L-type and T-type Ca2+
      channels (LTCC and TTCC). Digoxin administration in the iron-overloaded rat model
      deteriorated antioxidative parameters and increased iron entry into heart tissue
      at higher doses. Therefore, in patients with beta thalassaemia major, digoxin
      must be administered with great care and serum iron and ferritin must be
      regularly monitored.

PMID- 30108633
TI  - Evolutionary ecology of chemosensation and its role in sensory drive.
AB  - All behaviors of an organism are rooted in sensory processing of signals from its
      environment, and natural selection shapes sensory adaptations to ensure
      successful detection of cues that maximize fitness. Sensory drive, or divergent
      selection for efficient signal transmission among heterogeneous environments, has
      been a useful hypothesis for describing sensory adaptations, but its current
      scope has primarily focused on visual and acoustic sensory modalities.
      Chemosensation, the most widespread sensory modality in animals that includes the
      senses of smell and taste, is characterized by rapid evolution and has been
      linked to sensory adaptations to new environments in numerous lineages. Yet,
      olfaction and gustation have been largely underappreciated in light of the
      sensory drive hypothesis. Here, we examine why chemosensory systems have been
      overlooked and discuss the potential of chemosensation to shed new insight on the
      sensory drive hypothesis and vice versa. We provide suggestions for developing a
      framework to better incorporate studies of chemosensory adaptation that have the
      potential to shape a more complete, coherent, and holistic interpretation of the
      sensory drive.

PMID- 30108636
TI  - Periopathogens in atherosclerotic plaques of patients with both cardiovascular
      disease and chronic periodontitis.
AB  - BACKGROUND: Atherosclerosis and periodontitis are both chronic inflammatory
      diseases. Although a strong relationship between the two has already been
      established, the underlying mechanism is unknown. The present study was conducted
      aiming to detect the deoxyribonucleic acid (DNA) of Aggregatibacter
      actinomycetemcomitans (A.a), Campylobacter rectus (C.r), and Porphyromonas
      gingivalis (P.g) in subgingival and atherosclerotic plaques of patients with both
      chronic periodontitis and cardiovascular disease (CVD). METHODS: In this cross
      sectional study, patients with coronary artery disease (CAD) and moderate to
      severe periodontitis which were scheduled for coronary artery bypass grafting
      (CABG) were enrolled in the study. The subgingival plaques were collected before
      surgery. All samples were examined for the detection of selected periopathogens
      using polymerase chain reaction (PCR). RESULTS: The subgingival and
      atherosclerotic plaque samples of 23 patients were examined. The DNA of P.g, A.a,
      and C.r were found to be positive in 43.47%, 43.47%, and 78.26% of subgingival
      plaques, and 13.04%, 17.39%, and 8.69% of atherosclerotic plaques, respectively.
      In all cases, the bacterial species found in atherosclerotic plaques were also
      found in the subgingival plaques of the same patient. CONCLUSION: This study
      demonstrated the presence of periopathogens in atherosclerotic plaques of
      patients with chronic periodontitis. More studies are required to ascertain the
      exact role of these periopathogens in atherosclerotic plaque formation.

PMID- 30108634
TI  - Reviewing guppy color vision: integrating the molecular and physiological
      variation in visual tuning of a classic system for sensory drive.
AB  - Sensory drive predicts coevolution of mate choice signals with the sensory
      systems detecting those signals. Guppies are a classic model for sensory drive as
      mate preferences based on coloration differ across individuals and populations. A
      large body of work has identified variation in color vision, yet we lack a direct
      tie between how such variation in color vision influences variation in color
      preference. Here we bring together studies that have investigated guppy vision
      over the past 40 years to: (1) highlight our current understanding of where
      variation occurs in the guppy color vision pathway and (2) suggest future avenues
      of research into sources of visual system variation that could influence guppy
      color preference. This will allow researchers to design careful studies that
      couple measures of color preference with measures of visual system variation from
      the same individual or population. Such studies will finally provide important
      answers as to what sets the direction and speed of mate preference evolution via
      sensory drive.

PMID- 30108637
TI  - Methods of sampling and sample size determination of a comprehensive integrated
      community-based interventional trial: Isfahan Healthy Heart Program.
AB  - BACKGROUND: The aim of this study was describing the sampling methods and sample
      size of the Isfahan Healthy Heart Program (IHHP) and its sub-studies in focus.
      METHODS: The IHHP was carried out between 2000 and 2007 in urban and rural areas
      in 3 districts, namely Isfahan and Najafabad (as the intervention areas), and
      Arak (as the reference area), Iran. It consisted of the 3 phases of baseline
      surveys during 2000-2001, interventions between 2002 and 2005, and post
      intervention surveys during 2006-2007 on 4 target groups (adults, health
      professionals, cardiac patients, children, and adolescents). During 2002 to 2005,
      4 evaluation studies were conducted to evaluate short-term results. An ongoing
      cohort study entitled the Isfahan Cohort Study was performed on those aged >= 35
      years at baseline in 2001 to access the risk of cardiovascular disease (CVD)
      occurrence. RESULTS: Using stratified random cluster methods, 12514, 5891, 4793,
      6096, 3012, and 9572 adults and 1946, 1999, 1427, 1223, 389, and 1992 adolescents
      were chosen in the 1st to 3rd phases. Furthermore, simple random sampling was
      used for selecting 923, 694, 1000, and 2015 health professionals and 814, 452,
      420, and 502 cardiac patients. A multistage sampling method was adopted for the
      collection of samples from parents of preschoolers and primary school children
      aged 2-10 years, adolescents' parents, and some teachers. A prospective cohort
      study was started on 6504 eligible individuals. CONCLUSION: The IHHP, as a
      comprehensive community-based interventional trial in Iran, among the few
      population-based studies around the world, has reasonable sampling methods and
      sample size.

PMID- 30108638
TI  - Cardiac and renal fibrosis and oxidative stress balance in lipopolysaccharide
      induced inflammation in male rats.
AB  - BACKGROUND: Subclinical inflammation induced by persistent exposure to
      lipopolysaccharide (LPS) is found in some clinical conditions such as obesity or
      diabetes. This study aimed to investigate the effect of recurrent LPS exposure on
      inflammatory markers, oxidative stress balance and cardiac and renal fibrosis in
      male rats. METHODS: Male Wistar rats were divided into control and LPS-treated.
      LPS (10 mg/kg/week) was injected intraperitoneally. After 4 weeks, left
      ventricles and kidneys were homogenized and stained with hematoxylin and eosin
      (H&E) and Masson trichrome for histological examination. Serum levels of nitrite,
      interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were measured
      and total thiol, malondialdehyde (MDA), superoxide dismutase (SOD) and catalase
      were evaluated in the heart and kidney homogenates. RESULTS: Serum inflammatory
      markers were higher in LPS group than control (nitrite: 37.0 +/- 2.2 vs. 25.5 +/-
      1.9 umol/l; IL-6: 84 +/- 3 vs. 98.0 +/- 4.4 pg/ml; TNF-alpha: 75.5 +/- 4.9 vs.
      85.3 +/- 4.7 pg/ml; respectively, P < 0.050). Evaluation of total thiol
      concentration (heart: 10.0 +/- 0.9 vs. 22.5 +/- 1.2; kidney: 7.0 +/- 0.5 vs. 27.8
      +/- 3.1 nmol/g tissue, respectively), catalase (heart: 0.18 +/- 0.03 vs. 0.66 +/-
      0.04; kidney: 0.17 +/- 0.03 vs. 0.73 +/- 0.03, U/g tissue, respectively) and SOD
      (heart: 8.01 +/- 0.70 vs. 12.3 +/- 0.4; kidney: 7.02 +/- 0.60 vs. 12.0 +/- 0.2,
      U/g tissue, respectively) showed lower levels in LPS-treated group compared to
      control; while MDA concentration in LPS group was higher than control (P < 0.05).
      Histopathological examination in LPS-treated group indicated infiltration of
      inflammatory cells and more collagen deposition in left ventricle wall and kidney
      compared to control group. CONCLUSION: We concluded that in clinical conditions
      with chronic LPS, cardiac and renal fibrosis occurs even in absence of preceding
      tissue injury due to imbalances in oxidative stress.

PMID- 30108639
TI  - Right ventricular (RV) echocardiographic parameters in patients with pulmonary
      thromboembolism (PTE).
AB  - BACKGROUND: Acute pulmonary thromboembolism (PTE) is a common disease with a high
      mortality rate, and a variable and nonspecific clinical presentation. To detect
      the nonspecific signs and symptoms associated with this condition, several right
      ventricular (RV) echocardiographic parameters have been proposed as practical
      marker. METHODS: This cross-sectional study was performed on 93 patients with PTE
      diagnosed by computed tomography (CT) angiography, and 57 patients with negative
      PTE based on CT angiography. During the experiment, all patients underwent both
      transthoracic echocardiography (TTE) and multi-slice CT pulmonary angiography.
      Transthoracic echocardiography measurements were obtained as patients went
      through both experimental procedures. These measurements were later compared
      between the patients with and without PTE. RESULTS: Tricuspid annulus plain
      systolic excursion (TAPSE) (1.65 +/- 0.09 vs. 2.00 +/- 0.08 cm, P < 0.001) and
      left ventricular (LV) end-diastolic diameter (4.54 +/- 0.26 vs. 5.40 +/- 0.24 cm,
      P < 0.001) were significantly lower in patients with PTE as compared to patients
      without it. Whereas, RV end-diastolic and end-systolic diameters at the papillary
      muscle levels (3.41 +/- 0.09 vs. 3.02 +/- 0.12 cm, and 2.48 +/- 0.08 vs. 2.16 +/-
      0.06 cm, respectively, P < 0.001 for both), and tricuspid valve (TV) annulus
      tissue Doppler imaging (TDI) measurements (6.02 +/- 0.10 vs. 5.78 +/- 0.14, P <
      0.001) were significantly greater in patients with PTE. On the other hand, no
      significant difference was found between the two groups of patients regarding
      pulmonary artery pressure (PAP) (P = 0.416), and RV fractional shortening (P =
      0.157). Moreover, our results indicated that RV/LV (cut-off point: 0.6898) had
      high sensitivity (93.5%), specificity (100%), positive predicting value (PPV)
      (100%), and negative predicting value (NPV) (90.4%) in diagnosing PTE.
      CONCLUSION: TTE may be valuable as a substitute diagnostic method for patients
      with PTE. This technique may also assist in detecting the severity of the
      illness, by evaluating RV/LV in cut-off point of 0.6898.

PMID- 30108640
TI  - Effect of cardiac rehabilitation on inflammation: A systematic review and meta
      analysis of controlled clinical trials.
AB  - BACKGROUND: This systematic review and meta-analysis aimed to assess the effect
      of cardiac rehabilitation (CR) on serum C-reactive protein (CRP) as an indicator
      of the inflammatory state and predictor of recurrent cardiovascular events.
      METHODS: PubMed, SCOPUS, Cochrane library, and Google Scholar databases were
      searched up to January 2014 for original articles which investigated the effect
      of CR on CRP among adult patients with previous cardiovascular events. The random
      effects model was used to assess the overall effect of CR on the variation in
      serum CRP levels. RESULTS: In the present systematic review and meta-analysis, 15
      studies were included. The analysis showed that CR might significantly reduce
      high-sensitivity CRP (hs-CRP) levels [Difference in means (DM) = -1.81 mg/l, 95%
      confidence interval (CI): -2.65, -0.98; P = 0.004). However, the heterogeneity
      between studies was significant (Cochran's Q test, P < 0.001, I-squared = 84.9%).
      To find the source of variation, the studies were categorized based on study
      design (quality) and duration. The negative effect was higher among studies which
      followed their participants for 3 weeks or less (DM = -2.75 mg/l, 95% CI: -3.86, 
      1.64; P < 0.001) compared to studies which investigated the effect of CR for 3-8
      weeks (DM = -0.89 mg/l, 95% CI: -1.35, -0.44; P < 0.001) and those which lasted
      more than 8 weeks (DM = -1.71 mg/l, 95% CI: -2.53, -0.89; P < 0.001). There was
      no evidence of heterogeneity when the categorization was based on the follow-up
      period. CONCLUSION: Both short- and long-term CR have resulted in improvement in
      serum hs-CRP levels. CR can be perceived as a beneficial tool to reduce
      inflammatory markers among patients with previous cardiac events.

PMID- 30108642
TI  - Trifascicular block as primary presentation of the cardiac amyloidosis; A rare
      case report.
AB  - BACKGROUND: Amyloidosis is a severe systemic disorder produces by the
      accumulation of inappropriately amyloid deposition in tissues. Cardiac
      involvement, as a main type of amyloidosis, has a major impact on prognosis. We
      describe a biopsy-proven cardiac amyloidosis in an old man with unexpected
      presentation. CASE REPORT: A 70-year-old man, with a complaint of severe
      weakness, lightheadedness, and lower limb paresthesia, was admitted to the
      emergency department. Electrocardiography revealed right bundle branch block and
      Trifascicular block. Echocardiography study showed a moderately increased
      thickness of left ventricular wall with concentric pattern as well. Laboratory
      investigations including serum and urine electrophoresis, and serum free light
      chain examination as immunofixation assay revealed that kappa chains predominated
      over lambda chains in a ratio of 3:2. Our patient with final diagnosis of amyloid
      light-chain (AL) amyloidosis underwent chemotherapy with melphalan combined with
      high-dose dexamethasone, CPHPC and monoclonal antibodies for 2 weeks. CONCLUSION:
      It shows that rapid diagnosis of AL amyloidosis can enhance the prognosis.
      Applying an optimal strategy for the treatment leads to effective therapy, too.

PMID- 30108641
TI  - Distal accesses in the hand (two novel techniques) for percutaneous coronary
      angiography and intervention.
AB  - BACKGROUND: Trans-radial and trans-ulnar accesses have been practiced and
      recommended as default and alternative techniques for coronary angiography and
      angioplasty in recent years. In this study, we present new innovative approaches
      using more distal access points, i.e. trans-snuff box and trans-palmar
      approaches. METHODS: We conducted dorsal hand access (trans-snuff box) for
      angiography and/or angioplasty on 235 patients, and trans-palmar access
      (superficial palmar branch of ulnar artery) on 175 patients in 3 hospitals in
      Isfahan City, Iran. RESULTS: In 221 patients out of 235 ones (94.1%) [men: 76.5%,
      age: 57.4 +/- 10.4 (years); women: 23.5%, age: 62.4 +/- 9.5 (years)], our
      procedure through snuff box (dorsal hand) was successfully performed. In 159
      patients out of 175 ones (90.8%) [men: 76.0%, age: 58.1 +/- 10.5 (years); women:
      24.0%, age: 61.2 +/- 9.6 (years)], our procedure through palmar artery was
      successfully performed. In total, the evaluated patients had mild pain (3.4% for
      snuff box, and 4.5% for palmar), ecchymosis in distal forearm (5.1% for snuff
      box, and 2.8% for palmar), with no major complications even one (amputation,
      infection, thrombosis, need for surgery, hand dysfunction, nerve palsy, and so
      forth). In addition, percutaneous coronary intervention (PCI) was done in 28.9%
      and 18.2% of cases via snuff box and palmar approaches, respectively. Meanwhile,
      hemostasis was very fast and easy with discharge time equivalent to other upper
      limb accesses. CONCLUSION: Although our procedures are at their early stages with
      about a follow-up period of 3-15 months, more researches are recommended to be
      conducted in forthcoming months and years, and this new innovative approaches
      could be suggested safe, feasible, and reliable with low complications.

PMID- 30108643
TI  - Retracted: Mechanism of Hepatoprotective Effect of Boesenbergia rotunda in
      Thioacetamide-Induced Liver Damage in Rats.
AB  - [This retracts the article DOI: 10.1155/2013/157456.].

PMID- 30108644
TI  - The Bioavailability and Pharmacokinetics of Silymarin SMEDDS Formulation Study in
      Healthy Thai Volunteers.
AB  - The present study aimed to determine the pharmacokinetic parameters and
      bioavailability of silymarin 140 mg SMEDDS formulation. An open-label, single
      dose pharmacokinetic study was conducted. Twelve healthy volunteers were included
      in the study. After the volunteers had fasted overnight for 10 h, a single-dose
      generic silymarin 140 mg SMEDDS soft capsule was administered. Then 10 ml blood
      samples were taken at 0.0, 0.25, 0.50, 0.75, 1.0, 1.33, 1.67, 2.0, 2.5, 3.0, 4.0,
      6.0, 8.0, 10.0, and 12.0 h. The plasma silybin concentrations were analyzed using
      validated LC-MS/MS. The pharmacokinetic parameters were analyzed and calculated.
      The pharmacokinetic parameters were calculated after silymarin had been
      administered as a single capsule. The mean (range) Cmax was 812.43 (259.47
      1505.47) ng/ml at 0.80 (0.25-1.67) h (tmax). The mean (range) AUC0-t and AUC0-inf
      were 658.80 (268.29-1045.01) ng.h/ml and 676.98 (274.10-1050.96) ng.h/ml,
      respectively. The mean ke and t1/2 were 0.5386 h-1 and 1.91 h, respectively. The
      silymarin SMEDDS formulation soft capsule showed rapid absorption and high oral
      bioavailability.

PMID- 30108645
TI  - ETAS(r)50 Attenuates Ultraviolet-B-Induced Interleukin-6 Expression by
      Suppressing Akt Phosphorylation in Normal Human Dermal Fibroblasts.
AB  - We recently reported that ETAS 50, a standardized extract from the Asparagus
      officinalis stem, exerted anti-inflammatory effects on ultraviolet-B- (UV-B-)
      irradiated normal human dermal fibroblasts (NHDFs) by inhibiting nuclear factor
      kappaB p65 nuclear import and the resulting interleukin-1beta (IL-1beta)
      expression. To further elucidate the antiphotoaging potency of ETAS 50, we
      examined the anti-inflammatory effects on UV-B-irradiated NHDFs by focusing on
      the stress-activated mitogen-activated protein kinase (MAPK) and Akt signaling
      pathways. NHDFs were treated with 1 mg/mL of ETAS 50 or dextrin (vehicle control)
      after UV-B irradiation (20 mJ/cm2) for different time periods. Phosphorylation
      levels of c-Jun N-terminal kinase (JNK), p38 MAPK, and Akt were analyzed by
      western blotting. IL-6 mRNA levels were analyzed by real-time polymerase chain
      reaction. UV-B-irradiated NHDFs showed increased phosphorylation levels of JNK,
      p38 MAPK, and Akt, as well as increased mRNA levels of IL-6. ETAS 50 treatment
      after UV-B irradiation suppressed the increased phosphorylation levels of Akt
      without affecting those of JNK and p38 MAPK. ETAS 50 as well as Akt inhibitor
      Perifosine repressed UV-B irradiation-induced IL-6 mRNA expression. These results
      suggest that ETAS 50 treatment represses UV-B irradiation-induced IL-6 expression
      by suppressing Akt phosphorylation. The present findings demonstrate the
      potential of ETAS 50 to prevent photoaging by attenuating UV-B irradiation
      induced proinflammatory responses in skin fibroblasts.

PMID- 30108646
TI  - Effects of Tiaozhi Granule on Regulation of Autophagy Levels in HUVECs.
AB  - Sera from the rats with Tiaozhi granule treatment were collected. Human umbilical
      vein endothelial cells (HUVECs) were incubated with different dosage of sera with
      Tiaozhi granule for 48 hours. Rapamycin or angiotensin II was applied to activate
      autophagy in HUVECs with or without different dosages of sera of Tiaozhi granule.
      The mRNA expressions of Atg5, Atg7, Beclin-1, and mammal target of rapamycin
      (mTOR) were detected by real-time PCR. Autophagic flux markers (protein
      expression of LC3, Beclin-1, and p62) were examined by western blot analyses. The
      number of autophagosomes was visualized by immunofluorescence analysis with LC3
      II labelling. Results showed that Tiaozhi granule sera increase cell autophagic
      levels by increase of mRNA of Atg5, Atg7, Beclin-1, and mTOR and increase of
      autophagic flux and also number of autophagosomes. However, in response to
      rapamycin or Ang II stimulation, activated autophagic levels were alleviated by
      Tiaozhi granule sera by reduction of mRNA of Atg5, Atg7, Beclin-1, mTOR,
      autophagic flux, and also number of autophagosomes. Our present data demonstrate
      that Tiaozhi granule plays a dual role in response to different cell conditions,
      which is to increase cell autophagy under physiological condition and to suppress
      cell excessive autophagy under pathological condition.

PMID- 30108647
TI  - Exploring the Therapeutic Ability of Fenugreek against Type 2 Diabetes and Breast
      Cancer Employing Molecular Docking and Molecular Dynamics Simulations.
AB  - Fenugreek (Trigonella foenum-graecum) is used as a spice throughout the world. It
      is known for its medicinal properties such as antidiabetic, anticarcinogenic, and
      immunological activities. The present study shows the properties and the
      nutritional quality of fenugreek seed extract and focuses on screening of active
      compounds in drug designing for type 2 diabetes and breast cancer. Quantitative
      analysis was used to calculate the percentages of protein, carbohydrates
      moisture, fatty acid, galactomannan, oil, and amino acid. Phytochemical analysis
      revealed the presence of flavonoids, terpenoids, phenols, proteins, saponins, and
      tannins in fenugreek seed extracts. Molecular docking and molecular dynamics
      simulation-based computational drug discovery methods were employed to address
      the role of fenugreek seed constituents against type 2 diabetes and breast
      cancer. The computational results reveal that the compound galactomannan can be
      ascribed as potential drug candidate against breast cancer and type 2 diabetes
      rendered by higher molecular dock scores, stable molecular dynamics (MD)
      simulations results, and lower binding energy calculations.

PMID- 30108648
TI  - In Vitro Inhibition of alpha-Amylase and alpha-Glucosidase by Extracts from
      Psiadia punctulata and Meriandra bengalensis.
AB  - Background: This research assessed the in vitro antidiabetic activity and
      phytochemical constituents of the traditionally used medicinal plants, Psiadia
      punctulata and Meriandra bengalensis. Method: The leaves of both plants were
      subjected to cold extraction method using 70% ethanol and hot Soxhlet extraction
      using n-hexane, chloroform, methanol, and distilled water. The extracts were
      studied for their effect on glucose transport across yeast cells and inhibition
      of alpha-amylase and alpha-glucosidase enzyme activities. Thin-layer
      chromatographic analysis of ethanol extract was also undertaken. Results: The
      results of yeast glucose uptake assay revealed that extracts from both plants had
      a maximum increase in glucose uptake at the 25mM glucose concentration with a
      maximum dose of 2000MUg/ml plant extract. The ethanol extract of P. punctulata
      and aqueous extract of M. bengalensis showed a high activity of 68% and 96%,
      respectively, at 25mM and 2000MUg/ml of glucose and extract concentration. P.
      punctulata exerted peak inhibition activity of alpha-amylase of 37.5 +/- 3% mg/dl
      (IC50 = 0.523 mg/dl) for methanol and distilled water extract at 0.5 mg/dl,
      respectively. M. bengalensis methanol extract exhibited the highest inhibition
      activity of 38 +/- 8 % mg/dl (IC50 = 0.543 mg/dl) at 0.5 mg/dl. In the alpha
      glucosidase inhibition assay, the methanolic extract of P. punctulata exhibited
      the highest inhibitory activity of 17.29 +/- 9% mg/dl (IC50 = 0.761 mg/dl) at
      0.5mg/dl. The chloroform extract of M. bengalensis had the highest inhibitory
      activity of 30 +/- 5% mg/dl (IC50 = 0.6mg/dl) at 0.5 mg/dL. Phytochemical
      analysis of the different extracts of P. punctulata and M. bengalensis revealed
      the presence of flavonoids, alkaloids, tannins, saponins, phytosterols, and
      carbohydrates. Thin-layer chromatography analysis of ethanolic extract of both
      plants indicated presence of 15 and 17 spots for P. punctulata and M. bengalensis
      respectively. Conclusion: P. punctulata and M. bengalensis extracts have moderate
      inhibitory activity against pancreatic alpha-amylase and relatively low
      inhibitory activities against alpha-glucosidase. The observed effects may be
      associated with the presence of flavonoids, saponins, and alkaloids. Additional
      in vivo analysis, toxicological studies, isolation, and structural
      characterization of the phytomolecules identified in this study and molecular
      docking studies should be undertaken.

PMID- 30108649
TI  - Plants Used by Bapedi Traditional Healers to Treat Asthma and Related Symptoms in
      Limpopo Province, South Africa.
AB  - To the best of our knowledge there are presently no ethnobotanical surveys
      focusing on the utilisation of herbal remedies for asthma in South Africa. The
      present study is therefore an attempt to fill this gap in knowledge. A total of
      140 Bapedi traditional healers (THs) practicing in the Capricorn, Sekhukhune, and
      Waterberg districts of the Limpopo Province (South Africa) were queried using
      semistructured questionnaires, supplemented by field observations during face-to
      face interview. A total of 104 medicinal plant species (92 indigenous and 12
      exotics) belonging to 92 genera, distributed across 54 botanical families, mostly
      the Asteraceae and Fabaceae (18.5%, for each) as well as Malvaceae (12.9%), were
      used as antiasthmatics and related symptoms by these THs. Most of the plants were
      trees and herbs (37.5%, for each), with root (57%), leaf (15.8%), and bark
      (7.5%), respectively, being the saliently used parts for preparation of remedies.
      Clerodendrum ternatum, Cryptocarya transvaalensis, Lasiosiphon caffer, Enicostema
      axillare, Mimusops obovata, Sclerocarya birrea, and Stylochaeton natalensis were
      widely used and valued by all THs across the surveyed districts. Furthermore,
      these taxa also scored both the highest use value and fidelity level indexes as
      asthma therapies. Overall, the larger number of species documented in the present
      study is recorded for the first time in literature as asthma and/or related
      symptoms remedies. Our study finding generally contributes towards an
      establishment of South African database of herbal therapies used traditionally
      against these conditions.

PMID- 30108650
TI  - Traditional Mongolian, Traditional Chinese, and Western Medicine Hospitals:
      System Review and Patient Survey on Expectations and Perceptions of Quality of
      Healthcare in Inner Mongolia, China.
AB  - Background: In Inner Mongolia of China, traditional Mongolian medicine (TMM),
      traditional Chinese medicine (TCM), and western medicine (WM) are all supported
      by the government. This study compares the background and performance of these
      three types of medicines. Methods: The World Health Organization's Six Building
      Blocks framework was used for the system review. Data were collected from
      literature review and key informant interviews. A cross-sectional survey was
      conducted in three types of hospitals at the provincial, municipal (city), and
      prefectural (county) levels from April to August, 2016. Eight hospitals were
      included and, within each one, patients from four outpatient departments were
      selected. A total of 1,322 patients were interviewed about their expectations and
      perceptions of the health service. Results: Government support for TMM includes
      higher budget allocation and a higher reimbursement rate. TMM is preferred by
      Mongolian people, those living in pasturing areas, and those seeking treatment
      for musculoskeletal problems/injuries. Patients attending TMM hospitals had the
      highest expectations and perceptions of the health service in general. However,
      human resources and research capacity of TMM are relatively limited. Conclusion:
      To further enhance the role of the popular TMM for local minority's health, human
      resources and research capacity strengthening are essential.

PMID- 30108651
TI  - Bufadienolides from Venenum Bufonis Inhibit mTOR-Mediated Cyclin D1 and
      Retinoblastoma Protein Leading to Arrest of Cell Cycle in Cancer Cells.
AB  - Objective: Bufadienolides, the main components in Venenum Bufonis secreted from
      toads, have been proved to be with significant anticancer activity aside from the
      positive inotropic action as cardenolides. Here an underlying anticancer
      mechanism was further elucidated for an injection made from Venenum Bufonis
      containing nine bufadienolides. Methods: One solution reagent and cell cycle
      analyses were for determining effect of bufadienolides on cancer cells. Western
      blotting was used for protein expression. Results: Bufadienolides inhibit cell
      proliferation and arrest cells in G1 phase. Bufadienolides also inhibit the
      mammalian target of rapamycin (mTOR) signaling pathway, which is evidenced by the
      data that bufadienolides inhibit type I insulin-like growth factor- (IGF-1-)
      activated phosphorylation of mTOR by a concentration- and time-dependent way, as
      well as phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation
      factor 4E (eIF4E) binding protein 1 (4E-BP1). Subsequent results indicated that
      cyclin D1 expression and phosphorylation of retinoblastoma protein (Rb)-two
      characterized regulators in cell cycle of G1-are also inhibited and the process
      is dependent on mTOR pathway. Conclusion: Bufadienolides inhibit proliferation
      partially due to arresting cell cycle in G1 phase, which is mediated by
      inhibiting mTOR-cyclin D1/Rb signal pathway.

PMID- 30108652
TI  - The Relationship between Compound Danshen Dripping Pills with Isosorbide
      Mononitrate in the Treatment of Elderly Patients with Unstable Angina Pectoris.
AB  - Objective: To evaluate the clinical efficacy and safety of Compound Danshen
      Dripping Pill (CDDP) and Isosorbide Mononitrate (ISMN) in the treatment of
      unstable angina pectoris (UAP) in the elderly. Materials and Methods: CNKI,
      Wanfang, VIP, CBM, and PubMed databases were searched for appropriate articles
      without language limitations on keywords. RevMan 5.3 software was used to perform
      the meta-analysis. Results: This analysis compared CDDP with ISMN of 21
      randomized controlled trials (RCTs) that involved a total of 2356 patients with
      UAP. When the treatment lasted for four weeks, the clinical effective rate was OR
      = 3.97, 95% CI = 2.97, 5.30, and P < 0.00001, the ECG efficiency was OR = 3.43,
      95% CI = 2.13, 5.53, and P < 0.00001, and incidence of adverse reactions was OR =
      0.73, 95% CI = 0.52, 1.04, and P = 0.08 > 0.05. When the treatment lasted for
      eight weeks, clinical efficiency rate was OR = 4.22, 95% CI = 2.37, 3.79, and P <
      0.00001, incidence of adverse reactions was OR = 0.58, 95% CI = 0.26, 1.27, and P
      = 0.17 > 0.05, whole blood low-cut blood viscosity was SMD = -0.61 and 95% CI 
      1.60, 0.38, whole blood high-cut blood viscosity was SMD = -0.38 and 95% CI 
      0.97, 0.21, and blood cells specific volume was SMD = -0.80 and 95% CI -2.61,
      1.01. Conclusion: Based on this meta-analysis, the CDDP was superior to ISMN with
      UAP in the elderly. However, there is still a need to further verify the clinical
      efficacy and safety of CDDP with more strictly designed RCTs with large sample
      and multiple centers in the future.

PMID- 30108653
TI  - Development of a Traditional Chinese Medicine Syndrome-Specific Scale for
      Ulcerative Colitis: The Large Intestine Dampness-Heat Syndrome Questionnaire.
AB  - The aim of this study was to develop and validate the large intestine dampness
      heat syndrome questionnaire (LIDHSQ) for patients with ulcerative colitis (UC).
      The domains and items of the LIDHSQ were developed according to standard
      procedures, namely, construct definition, item generation, language testing,
      content validity, pilot study, and validation study. At first, a total of 20
      items in 3 domains were generated based on literature review and expert
      consultation. After the item selection, the LIDHSQ contains 11 items in three
      domains: disease-related domain (diarrhoea, abdominal pain, bloody purulent
      stool, and mucus stool), heat domain (fever, dry mouth, red tongue, yellow fur,
      and anal burning), and dampness domain (greasy fur and defecation disorder). The
      Cronbach's alphas of all domains were greater than 0.6. All of the intraclass
      correlation coefficients were greater than 0.8. The LIDHSQ and domain scores of
      the patients with LIDHS were higher than those of the patients with other
      syndromes (P < 0.001). The area under the receiver operating characteristic curve
      of the LIDHSQ was 0.900, with a 95% confidence interval of 0.872-0.928. When the
      cut-off value of the LIDHSQ was >= 7, the sensitivity and specificity were 0.867
      and 0.854, respectively. The LIDHSQ is valid and reliable for measuring LIDHS in
      UC patients with good diagnostic efficacy. We recommend the use of the LIDHSQ in
      Chinese UC patients.

PMID- 30108654
TI  - The Effect of Pluchea indica (L.) Less. Tea on Adipogenesis in 3T3-L1 Adipocytes
      and Lipase Activity.
AB  - Obesity and hyperlipidemia are a major problem in the world. Pluchea indica (L.)
      Less. tea (PIT) is a beverage that has various indications. This study focused on
      the effect of the PIT on inhibiting adipogenesis of 3T3-L1 cells and pancreatic
      lipase enzyme activity. The viability of 3T3-L1 cells was not significantly
      decreased after exposure to 200 to 1000 MUg mL-1 PIT compared to controls (p >
      0.05). The PIT at 750 to 1000 MUg mL-1 exhibited a significantly reduced lipid
      accumulation compared to the control (p < 0.05). The inhibitory effects of the
      PIT at 250 to 1000 MUg mL-1 on lipase activity were significantly increased
      compared to control (p < 0.05). The FTIR results showed that the integrated areas
      of lipids, proteins, nucleic acids, glycogen, and carbohydrates of the PIT
      treated 3T3-L1 adipocytes were significantly lower than the untreated 3T3-L1
      adipocytes (p < 0.05). These findings may indicate that the PIT is not only
      capable of inhibiting lipids and carbohydrate accumulation in adipocytes but also
      has a potential to inhibit pancreatic lipase activity. So, the PIT may be further
      developed to the novel lipid-lowering herbal supplement for the management of
      overweight or obesity.

PMID- 30108655
TI  - In Vitro Antidiabetic Activity and Mechanism of Action of Brachylaena elliptica
      (Thunb.) DC.
AB  - In South Africa, the number of people suffering from diabetes is believed to be
      rising steadily and the current antidiabetic therapies are frequently reported to
      have adverse side effects. Ethnomedicinal plant use has shown promise for the
      development of cheaper, cost-effective antidiabetic agents with fewer side
      effects. The aim of this study was to investigate the antidiabetic activity and
      mechanism of action of aqueous leaf extract prepared from Brachylaena elliptica.
      The potential of the extract for cytotoxicity was evaluated using MTT assay in
      HepG2 cells. The effects of the plant extract on glucose utilization in HepG2
      cells and L6 myotubes, triglyceride accumulation in 3T3-L1, INS-1 proliferation,
      glucose metabolism in INS-1 cells, and NO production in RAW macrophages were also
      investigated using cell culture procedures. The inhibitory effects of the extract
      on the activities of different enzymes including alpha-amylase, alpha
      glucosidase, pancreatic lipase, dipeptidyl peptidase IV (DPP-IV), collagenase,
      and CYP3A4 enzymes were evaluated. The extract also tested against protein
      glycation using standard published procedure. The plant extract displayed low
      level of toxicity, where both concentrations tested did not induce 50% cell
      death. The extract caused a significant increase in glucose uptake in HepG2 liver
      cells, with efficacy significantly higher than the positive control, berberine.
      The crude extract also displayed no significant effect on muscle glucose uptake,
      triglyceride accumulation in 3T3-L1, glucose metabolism in INS-1 cells, alpha
      amylase, alpha-glucosidase, DPP-IV, lipase, protein glycation, and collagenase
      compared to the respective positive controls. The extract displayed a
      proliferative effect on INS-1 cells at 25 MUg/ml when compared to the negative
      control. The plant also produced a concentration-dependent reduction in NO
      production in RAW macrophages and also demonstrated weak significant inhibition
      on CYP3A4 activity. The findings provide evidence that B. elliptica possess
      antidiabetic activity and appear to exact its hypoglycemic effect independent of
      insulin.

PMID- 30108656
TI  - Danggui Sini Decoction Protected Islet Endothelial Cell Survival from Hypoxic
      Damage via PI3K/Akt/eNOS Pathway.
AB  - Danggui Sini decoction (DSD) is a traditional Chinese decoction, which is wildly
      applied and showed to be effective in ameliorating ischemia-related symptoms.
      However, the mechanisms of DSD action in ischemic damage remain to be fully
      clarified. Pancreatic islet endothelial cells are pivotal constituent of islet
      microvasculature, with high vulnerability to hypoxic injuries. Here, using MST1
      cell, a pancreatic islet endothelial cell-line, as a model, we investigated the
      effects of DSD on hypoxia-stimulated endothelial cell lesions and its underlying
      mechanisms. We found that DSD-Containing Serum (DSD-CS), collected from DSD
      treated rats, could efficiently protect MST1 survival and proliferation from
      Cobalt chloride (CoCl2) induced damage, including cell viability, proliferation,
      and tube formation. Furthermore, DSD-CS restored the activity of PI3K/Akt/eNOS
      signaling inhibited by CoCl2 in MST1 cells. The protective effect of DSD-CS could
      be blocked by the specific PI3K/Akt/eNOS inhibitor LY294002, suggesting that DSD
      CS protection of MST1 cell survival from hypoxia was mediated by PI3K/Akt/eNOS
      pathway. In conclusion, DSD treatment protected MST1 survival from hypoxic
      injuries via PI3K/Akt/eNOS pathway, indicating its role in protecting
      microvascular endothelial cells.

PMID- 30108657
TI  - Combination of Epicatechin 3-Gallate from Euphorbia hirta and Cefepime Promotes
      Potential Synergistic Eradication Action against Resistant Clinical Isolate of
      Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is naturally resistant to many classes of antipseudomonal
      antibiotics due to the species ability to easily acquire resistance. Plant-based
      antibacterial agent in combination with the existing antibiotic proposes an
      alternative treatment regimen for the eradication of resistant bacterial
      infections. The antibacterial effects of the isolated epicatechin 3-gallate
      compound from Euphorbia hirta in combination with cefepime were investigated in
      vitro against resistant P. aeruginosa. The fractional inhibitory concentration
      index of the combination was determined using checkerboard broth microdilution
      method. Epicatechin 3-gallate combined with cefepime had produced synergistic
      effect against P. aeruginosa (with average FIC index of 0.24). The MIC of
      epicatechin 3-gallate was effectively reduced to MIC/4, MIC/8, MIC/16, and MIC/32
      in the presence of cefepime. Time-kill study of epicatechin 3-gallate combined
      with cefepime exhibited remarkable bactericidal activity where the eradication of
      P. aeruginosa occurred within 4 h of treatment. Scanning electron micrographs
      revealed apparent cell membrane damage and leakage of cytoplasmic contents from
      P. aeruginosa cells which eventually led to the cell lysis after the combination
      treatment of epicatechin 3-gallate and cefepime. The potential of epicatechin 3
      gallate to act synergistically with cefepime against clinically resistant P.
      aeruginosa strain possibly will maximize the successful outcomes when choosing
      empirical antibiotic treatment in hospitals or health care institutions.

PMID- 30108658
TI  - Gut Microbiota Play an Essential Role in the Antidiabetic Effects of Rhein.
AB  - It is clear that the gut microbiota can affect host metabolism and alterations of
      the gut microbiota can link with metabolic disease. Rhein has been used in
      traditional Chinese medicine with putative antidiabetic effects. Here we show
      that oral administration of rhein for 6 weeks can significantly reduce fasting
      blood glucose (FBG) level (8.30 +/- 4.52 mmol/l versus 18.89 +/- 6.06 mmol/l, p <
      0.01), elevate the active glucagon-like peptide 1 (GLP-1) level (22.21 +/- 2.61
      pmol/l verss 14.46 +/- 5.22 pmol/l, p < 0.05), and increase the number of L-cells
      in the terminal ileum. The antidiabetic effect of rhein is abrogated in db/db
      mice treated with rhein in combination with broad-spectrum antibiotics. We
      observed that the abundance of the Bacteroidetes is increased in mice treated
      with rhein (0.361+/-0.022 versus 0.185 +/- 0.055, p < 0.05,). In addition, there
      is no significant difference in diversity between rhein-treated groups and the
      controls (Shannon index: p = 0.88; Simpson index: p = 0.86). Taken together, our
      results indicate that modulation of the gut microbiota may play an essential role
      in the antidiabetic effects of rhein.

PMID- 30108659
TI  - Vasorelaxant and Hypotensive Effects of Cheonwangbosimdan in SD and SHR Rats.
AB  - Historically, traditional herbal medicines (THMs) have been the conventional
      treatment strategy in the Korean medical system for treating many diseases.
      However, THMs have rarely been used to treat hypertension, and moreover few
      studies have investigated the interaction of blood pressure with the
      coadministration of synthetic antihypertensives. We aimed to evaluate the
      vasorelaxant and hypotensive effects of the traditional herbal prescription
      Cheonwangbosimdan (CWBSD; "Tianwangbuxindan" in Chinese) and the combination of
      CWBSD with amlodipine. CWBSD was extracted with distilled water at 100 degrees C
      for 2 h. To investigate vasorelaxant activities, CWBSD with amlodipine (10
      MUg/ml) was added cumulatively (10-1,000 MUg/ml) to isolated rat aortic rings
      precontracted using phenylephrine or potassium chloride in organ chambers. To
      investigate hypotensive effects, CWBSD (2,476 mg/kg) was orally administered with
      or without amlodipine (5 mg/kg) to spontaneously hypertensive rats (SHRs). CWBSD
      increased the relaxation of rat aortic rings induced by amlodipine (P < 0.01). In
      vivo, CWBSD coadministration with amlodipine also significantly decreased the
      blood pressure of SHRs compared to the amlodipine-treated group. These results
      suggested that CWBSD could be a useful herbal prescription to treat hypertension
      and we recommend establishing guidelines for the use of herbal medicines in
      conjunction with antihypertensive drugs, including amlodipine.

PMID- 30108660
TI  - Effectiveness and Safety of Compound Chinese Medicine plus Routine Western
      Medicine in In-Stent Restenosis: A Meta-Analysis and Systematic Review.
AB  - Objective: To examine the effects and safety of oral compound Chinese medicine
      (CCM) plus routine western medicine (RWM) in in-stent restenosis (ISR). Methods:
      Various electronic databases (CBM, CNKI, VIP, Wanfang, PubMed, EMBASE, and
      Cochrane Library) were searched until April 2017. The quality of the included
      studies was evaluated, and meta-analyses were performed using RevMan5.3 and STATA
      12.0 software. Moreover, funnel plot and Egger's publication bias plots were
      analysed to identify publication bias and adverse reactions were reported. A
      sensitive analysis was carried out according to the quality score. Results: In
      all, 40 RCTs involving 4536 patients were selected for this review. The pooled
      estimates of three studies showed that the benefit to the number of ISRs (NoR)
      was more substantial for CCM plus RWM than for RWM alone (RR 0.24, 95% CI 0.10 to
      0.57, P = 0.001; I2 = 0%, P = 0.81). The rate of ISR was significantly lower for
      CCM plus RWM than for the same RWM alone (RR 0.44, 95% CI 0.37 to 0.53, P <
      0.00001; I2 = 0%, P = 0.95). CCM plus RWM benefitted the rate of ISR when a CM
      placebo plus RWM was used as the control intervention (RR 0.34, 95% CI 0.20 to
      0.57, P < 0.0001; I2 = 0%, P = 0.95). The difference of adverse reactions was not
      significant. For secondary outcomes, the CCM plus RWM group did not reduce the
      rates of revascularization and cardiac death, but it did reduce the rate of
      recurrent angina over the results observed in the RWM alone group. In addition,
      funnel plot and Egger's publication bias plot indicated that there was
      publication bias. The association between the use of CCM plus RWM and RWM alone
      remained significant after the sensitivity analysis excluding studies with low
      quality score (quality score ? 4) with a pooled RR of 0.41 (95% CI, 0.34-0.50).
      Conclusion: Oral CCM plus RWM clearly benefitted patients with percutaneous
      coronary intervention (PCI) because it prevented and treated ISR better than was
      observed for either RWM alone or a CM placebo plus RWM.

PMID- 30108661
TI  - A New Strategy to Uncover the Anticancer Mechanism of Chinese Compound Formula by
      Integrating Systems Pharmacology and Bioinformatics.
AB  - Currently, cancer has become one of the major refractory diseases threatening
      human health. Complementary and alternative medicine (CAM) has gradually become
      an alternative choice for patients, which can be attributed to the high cost of
      leading cancer treatments (including surgery, radiotherapy, and chemotherapy) and
      the severe related adverse effects. As a critical component of CAM, traditional
      Chinese medicine (TCM) has increasing application in preventing and treating
      cancer over the past few decades. Huanglian Jiedu Decoction (HJD), a classical
      Chinese compound formula, has been recognized to exert a beneficial effect on
      cancer treatment, with few adverse effects reported. Nevertheless, the precise
      molecular mechanism remains unclear yet. In this study, we had integrated systems
      pharmacology and bioinformatics to explore the major active ingredients against
      cancer, targets for cancer treatment, and the related mechanisms of action. These
      targets were scrutinized using web-based Gene SeT Analysis Toolkit (WebGestalt),
      and 10 KEGG pathways were identified by enrichment analysis. Refined analysis of
      the KEGG pathways indicated that the anticancer effect of HJD showed a functional
      correlation with the p53 signaling pathway; moreover, HJD had potential
      therapeutic effect on prostate cancer (PCa) and small cell lung cancer (SCLC).
      Afterwards, genetic alterations and survival analysis of key targets for cancer
      treatment were examined in both PCa and SCLC. Our results suggested that such
      integrated research strategy might serve as a new paradigm to guide future
      research on Chinese compound formula. Importantly, such strategy contributes to
      studying the anticancer effect and the mechanisms of action of Chinese compound
      formula, which has also laid down the foundation for clinical application.

PMID- 30108662
TI  - Jian-Pi-Yi-Shen Formula Regulates Inflammatory Cytokines Production in 5/6
      Nephrectomized Rats via Suppression of NF-kappaB Activation.
AB  - Jian-Pi-Yi-Shen formula (JPYSF) is a Chinese herbal decoction used for treating
      chronic kidney disease (CKD) for over 20 years with good efficiency. However, the
      mechanism lacks solid evidence. In the present study, we tested the hypothesis
      that JPYSF may retard CKD progression via inhibition of inflammation in 5/6
      nephrectomy (5/6 Nx) rat model. The 5/6 Nx rats were randomly divided into 2
      groups: 5/6 Nx group and JPYSF group. Sham-operated rats served as control. JPYSF
      (2.06 g/kg/d) were administrated by gavage to 5/6 Nx rats daily for 6 weeks.
      Results showed that JPYSF treatment significantly improved kidney function and
      pathological injury in 5/6 Nx rats. Multiplex analysis of cytokines revealed that
      JPYSF reduced proinflammatory cytokines and increased anti-inflammatory cytokine
      production. Furthermore, JPYSF inhibited the activation of nuclear factor-kappa B
      (NF-kappaB) signaling pathway. In conclusion, our data demonstrated that JPYSF
      remarkably retards development and progression of CKD in a 5/6 Nx rat model,
      which may be associated with inhibition of inflammation via NF-kappaB signaling
      pathway.

PMID- 30108664
TI  - Focus on advanced materials for energy harvesting: prospects and approaches of
      energy harvesting technologies.

PMID- 30108663
TI  - Tualang Honey Reduced Neuroinflammation and Caspase-3 Activity in Rat Brain after
      Kainic Acid-Induced Status Epilepticus.
AB  - The protective effect of tualang honey (TH) on neuroinflammation and caspase-3
      activity in rat cerebral cortex, cerebellum, and brainstem after kainic acid- (KA
      ) induced status epilepticus was investigated. Male Sprague-Dawley rats were
      pretreated orally with TH (1.0 g/kg body weight) five times at 12 h intervals. KA
      (15 mg/kg body weight) was injected subcutaneously 30 min after last oral
      treatment. Rats were sacrificed at 2 h, 24 h, and 48 h after KA administration.
      Neuroinflammation markers and caspase-3 activity were analyzed in different brain
      regions 2 h, 24 h, and 48 h after KA administration. Administration of KA induced
      epileptic seizures. KA caused significant (p < 0.05) increase in the level of
      tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), glial
      fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF-1), and
      cyclooxygenase-2 (COX-2) and increase in the caspase-3 activity in the rat
      cerebral cortex, cerebellum, and brainstem at multiple time points. Pretreatment
      with TH significantly (p < 0.05) reduced the elevation of TNF-alpha, IL-1beta,
      GFAP, AIF-1, and COX-2 level in those brain regions at multiple time points and
      attenuated the increased caspase-3 activity in the cerebral cortex. In
      conclusion, TH reduced neuroinflammation and caspase-3 activity after kainic acid
      (KA-) induced status epilepticus.

PMID- 30108666
TI  - Celebrating the 10th Anniversary of the International Journal of Therapeutic
      Massage and Bodywork.
AB  - From an informal conversation to a peer reviewed, open-access, indexed journal,
      we are now celebrating the 10th anniversary of the International Journal of
      Therapeutic Massage and Bodywork: Research, Education, and Practice. We celebrate
      the uniqueness of the Journal as the only fully open-access journal that
      addresses massage therapy and bodywork. Scholarly open-access journals have
      changed the face of scientific publishing in recent years: providing wider
      dissemination, allowing findings from taxpayer supported research to be available
      for free, and providing an avenue for researchers in the developing world to
      connect with researchers in developed countries. The editors of the Journal are
      regularly looking and soliciting articles from massage therapy researchers. This
      editorial describes the progress of the last ten years- from an article and
      readership standpoint-including changes in partnerships and increased visibility
      through social media.

PMID- 30108665
TI  - Mechanochemically assisted hydrothermal synthesis of Sn-substituted MFI-type
      silicates.
AB  - Substitution of Al atoms in a zeolite framework by catalytic metal atoms has
      attracted considerable attention because the catalytic behavior can be tuned by
      the substituted atoms. In the present study, Sn-substituted MFI-type silicates
      were synthesized using a hydrothermal reaction of an amorphous Si-O-Sn precursor
      prepared by mechanochemical grinding of SiO2 and Sn(OH)4. The mechanochemical
      treatment was found to be a key technique for obtaining the amorphous Si-O-Sn
      precursor, where tetrahedral Sn4+ species were incorporated into the amorphous
      matrix. The Sn content in the framework of the MFI-type silicates was
      successfully controlled by the initial HCl/Si molar ratio of the hydrothermal
      procedures. Optical reflectance measurements revealed that the Sn4+ ions were
      dispersedly incorporated into the silicate framework while preserving the initial
      tetrahedrally coordinated species. Infrared results imply that the resulting Sn
      substituted MFI-type silicate has Bronsted acid character. Precise control of the
      Bronsted and Lewis acid properties by Sn doping is a promising approach to the
      development of novel types of zeolite-based catalytic materials.

PMID- 30108668
TI  - Developing Capability: Transforming Massage Therapy Education through Inquiry
      based Learning.
AB  - Massage therapy education programs are responsible for preparing graduates for
      complex professional environments, while also ensuring graduates can access the
      profession by passing the regulatory body's standardized certification or
      licensing examination. Massage therapists are regulated health care professionals
      in four Canadian provinces. They are autonomous practitioners and an integral
      part of the health care regime for patients with complicated health
      presentations. As such, they must think critically about patients' presentations
      and determine the most appropriate care. This article describes the process
      undertaken by the faculty team of Humber College's Massage Therapy Program in an
      effort to transform the existing teaching and learning strategies by
      incorporating principles of inquiry-based learning (IBL).

PMID- 30108667
TI  - Myofascial Massage for Chronic Pain and Decreased Upper Extremity Mobility After
      Breast Cancer Surgery.
AB  - Background: Chronic localized pain and decreased upper extremity mobility
      commonly occur following breast cancer surgery and may persist despite use of
      pain medication and physical therapy. Purpose: We sought to determine the value
      of myofascial massage to address these pain and mobility limitations. Setting:
      The study took place at a clinical massage spa in the U.S. Midwest. The research
      was overseen by MetroHealth Medical Center's Institutional Review Board and Case
      Center for Reducing Health Disparities research staff. Participants: 21 women
      with persistent pain and mobility limitations 3-18 months following breast
      surgery. Research Design: We conducted a pilot randomized controlled trial where
      intervention patients received myofascial massages and control patients received
      relaxation massages. Intervention: Intervention participants received 16
      myofascial massage sessions over eight weeks that focused on the affected breast,
      chest, and shoulder areas. Control participants received 16 relaxation massage
      sessions over eight weeks that avoided the affected breast, chest, and shoulder
      areas. Participants completed a validated questionnaire at the beginning and end
      of the study that asked about pain, mobility, and quality of life. Main Outcome
      Measures: Outcome measures include change in self-reported pain, self-reported
      mobility, and three quality-of-life questions. Results: At baseline, intervention
      and control participants were similar in demographic and medical characteristics,
      pain and mobility ratings, and quality of life. Compared to control participants,
      intervention participants had more favorable changes in pain (-10.7 vs. +0.4, p <
      .001), mobility (-14.5 vs. -0.8, p < .001), and general health (+29.5 vs. -2.5, p
      = .002) after eight weeks. All intervention and control participants reported
      that receiving massage treatments was a positive experience. Conclusions:
      Myofascial massage is a promising treatment to address chronic pain and mobility
      limitations following breast cancer surgery. Further work in several areas is
      needed to confirm and expand on our study findings.

PMID- 30108669
TI  - The Potential Utility for Massage Therapy During Pregnancy to Decrease Stress and
      Tobacco Use.
AB  - Background: A significant number of women continue to smoke tobacco during
      pregnancy despite the increased risk of complications to fetal and infant
      development. Therefore, effective interventions are needed to assist pregnant
      women with the process of tobacco cessation. Traditional counseling programs have
      demonstrated some success; however, novel approaches that target stress as a
      mechanism in the maintenance of addiction would be valuable. Objective: To
      examine the role of stress in addiction and the utility of massage therapy to
      decrease stress during pregnancy. Conclusion: Preliminary evidence suggests
      massage therapy may be beneficial to decreasing tobacco use, and research in
      pregnant populations is needed.

PMID- 30108670
TI  - Molybdenum cofactor deficiency: Neuroimaging findings.
AB  - Molybdenum cofactor deficiency is an extremely rare and fatal metabolic disorder
      that should be considered in the differential diagnosis of hypoxic-ischemic
      encephalopathy. Magnetic resonance imaging findings are useful in diagnosis. The
      short-echo-time magnetic resonance spectrum was characterized by a total loss of
      signal and lipid and lactate peaks. In this case, conventional magnetic resonance
      imaging and magnetic resonance spectroscopy findings of this extremely rare
      disease whose pathophysiology was not known were presented.

PMID- 30108671
TI  - A rare manifestation of clinical T1 renal tumor with parasitic arterial supply
      from the superior mesenteric artery.
AB  - A 50-year-old man with von Hippel-Lindau syndrome who had undergone repeated
      tumor enucleation and transcatheter arterial embolization for multiple renal cell
      carcinomas (RCC) was referred to our hospital for percutaneous cryoablation (PCA)
      of an RCC of 42 mm in the midpole region of the right kidney. Transcatheter
      arterial embolization was planned prior to devascularize the RCC and selective
      angiography revealed parasitic arterial supply to the tumor by the ileocecal
      artery. Parasitic arterial supply to RCCs, particularly in patients with history
      of nephron-sparing treatment, can originate even from an intraperitoneal source
      and may lead to unexpected embolization.

PMID- 30108672
TI  - Adrenocortical adenoma manifesting as false-positive iodine accumulation in a
      patient with history of thyroid carcinoma.
AB  - A 47-year-old female diagnosed with well-differentiated papillary thyroid
      carcinoma was referred to our center for a 131Iodine whole body scintigraphy as
      follow-up. The patient had been previously treated with total thyroidectomy and
      ablative dose of 175mCi 131I three years ago. Diagnostic 131I scan showed a zone
      of radioiodine uptake in posterior aspect of the left upper quadrant of the
      abdomen. Spiral abdominal and pelvic CT scan showed an enhancing solid mass in
      superior aspect of the left adrenal gland, which was in favor of metastasis to
      the lymph node or an adrenal tumor. A biopsy was performed from the lesion.
      Histological examination of the surgical specimen was consistent with
      adrenocortical adenoma. Even though rare, adrenocortical adenoma should be
      included in the potential causes of false-positive results of radioiodine scans.

PMID- 30108673
TI  - Acute synchronous appendicitis and obstructing ureterolithiasis.
AB  - This is an unusual case of a patient presenting to the Emergency Room with right
      sided abdominal pain and subsequently 2 acute diagnoses were made. The patient
      had both acute appendicitis and acute ureterolithiasis.

PMID- 30108674
TI  - Urachal mucinous adenocarcinoma in the pelvic wall mimicking endometriosis.
AB  - We report the case of a 30-year-old woman who complained of a painful palpable
      mass. Magnetic resonance imaging revealed an ill-defined mass approximately 8 cm
      in diameter with internal microcytic components. The mass diffusely involved the
      subcutaneous tissues, the muscles of the pelvic wall, and urinary bladder via a
      postoperative scar and resembled endometriosis. The histopathologic diagnosis was
      mucinous adenocarcinoma arisen from the urachal remnant. This is a very rare case
      of urachal adenocarcinoma arising mainly in the pelvic wall and mimicking
      endometriosis on MRI.

PMID- 30108675
TI  - Multinodular and vacuolating neuronal tumor incidentally discovered in a young
      man: Conventional and advanced MRI features.
AB  - Multinodular and Vacuolating Neuronal Tumor (MVNT) has been included in the most
      recent (2016) World Health Organization Classification of Tumors of the Central
      Nervous System as unique cytoarchitectural pattern of gangliocytoma. We present a
      case of a MVNT incidentally discovered in a 22-year old male, who presented with
      seizures after a head injury. Conventional MRI revealed a left parietal lesion
      with characteristic tiny, coalescent, well-defined, non-enhancing nodules,
      located in the juxtacortical white matter with partial involvement of an
      otherwise normal adjacent cortex and characterized by slight relative increase of
      the cerebral blood volume (CBV), compared to the contralateral white matter
      (lesional CBV/contralateral CBV = 1.112) and mild increase of choline and
      reduction of NAA (lesional choline/creatine ratio =1.36 and choline/NAA
      ratio=0.77, compared to 0.87 and 0.51, respectively). The patient fully responded
      to treatment with phenytoin and a follow-up MRI, six months later, showed the
      lesion without any substantial difference.

PMID- 30108676
TI  - Diffuse periostitis as the primary presenting radiological finding in an AML
      patient with disease relapse.
AB  - Acute myelogenous leukemia is a hematologic malignancy defined by the presence of
      myeloid blasts causing bone marrow infiltration. Evaluation and workup of acute
      myelogenous leukemia is based on comprehensive medical history, physical
      examination, laboratory evaluation, and bone marrow sampling. Magnetic resonance
      (MR) imaging is the study of choice in the evaluation of this disease including
      the initial evaluation, treatment follow-up, and complications. Herein, we report
      a case of relapse of the acute myelogenic leukemia in an adult patient who
      presented with diffuse periostitis in his lower extremities diagnosed on MR
      imaging and confirmed on Technetium bone scan, which also showed periostitis
      along the bilateral humeri. To our knowledge, this was not previously reported in
      the English literature.

PMID- 30108677
TI  - A rapid caliber change in the inferior vena cava during multiphasic contrast
      enhanced computed tomography may signal an acute anaphylactic reaction to
      nonionic contrast medium.
AB  - Severe anaphylactic reactions to an intravenous nonionic iodine contrast medium
      (NICM) are uncommon but can result in permanent morbidity or death if not managed
      appropriately. An anaphylactic reaction to an NICM typically manifests as
      clinical symptoms that include an itchy nose, sneezing, and skin redness. To our
      knowledge, a rapid change in the caliber of the inferior vena cava (IVC) during
      multiphasic contrast-enhanced computed tomography (CT) has not been reported.
      Here, we report the computed tomographic findings in three cases of hypovolemic
      shock caused by an anaphylactic reaction to an NICM. We suspect that a decrease
      in caliber of the IVC during multiphasic contrast-enhanced CT may be a predictor
      of an allergic-like reaction to an NICM. Patients in whom physicians and
      radiographers detect a rapid caliber change in the IVC during multiphasic
      contrast-enhanced CT should be managed carefully.

PMID- 30108678
TI  - Embolization of hemorrhagic renal angiomyolipoma complicated by arteriovenous
      shunting: A case report.
AB  - Arteriovenous shunting associated with angiomyolipoma is an unusual entity, which
      carries important implications to embolization approach. We present a distinctive
      case involving a 41-year-old woman who presented with retroperitoneal hemorrhage
      relating to renal angiomyolipoma. During angiography for urgent embolization, a
      complex vascular supply with arteriovenous shunting was encountered.
      Superselective embolization using alcohol or small particles is the standard
      approach to definitive treatment of symptomatic angiomyolipoma; however; their
      use is precluded in the setting of arteriovenous shunt hemodynamics. In this
      case, a 2-step approach was employed by which the initial hemorrhage was treated
      with proximal embolization using large gelatin foam and metallic coils. This
      resulted in decreased flow through the arteriovenous shunt, allowing the use high
      viscosity ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide for
      definitive treatment.

PMID- 30108679
TI  - Desmoplasia in pancreatic ductal adenocarcinoma: insight into pathological
      function and therapeutic potential.
AB  - Extensive desmoplasia is a prominent feature of the pancreatic ductal
      adenocarcinoma (PDAC) microenvironment. Initially, studies demonstrated that
      desmoplasia promotes proliferation, invasion and chemoresistance in PDAC cells.
      While these findings suggested the therapeutic potential of targeting desmoplasia
      in PDAC, more recent studies utilizing genetically-engineered mouse models of
      PDAC, which lack key components of desmoplasia, demonstrated accelerated
      progression of PDAC. This contrast calls into question the paradigm that
      desmoplasia unilaterally promotes PDAC progression and the premise of desmoplasia
      targeted therapy. This review briefly examines the major reports of the tumor
      promoting and -restraining roles of desmoplasia in PDAC with commentary on the
      gaps in our current understanding of desmoplasia in PDAC. Additionally, we
      discuss the studies demonstrating the heterogeneous and multifaceted nature of
      desmoplasia in PDAC and advocate for future areas of research to thoroughly
      address the various facets of desmoplasia in PDAC, reconcile seemingly
      contradictory reports of the role of desmoplasia in PDAC progression, and
      discover aspects of desmoplasia that are therapeutically actionable.

PMID- 30108681
TI  - Identification of a panel of MYC and Tip60 co-regulated genes functioning
      primarily in cell cycle and DNA replication.
AB  - We recently reported that adenovirus E1A enhances MYC association with the
      NuA4/Tip60 histone acetyltransferase (HAT) complex to activate a panel of genes
      enriched for DNA replication and cell cycle. Genes from this panel are highly
      expressed in examined cancer cell lines when compared to normal fibroblasts. To
      further understand gene regulation in cancer by MYC and the NuA4 complex, we
      performed RNA-seq analysis of MD-MB231 breast cancer cells following knockdown of
      MYC or Tip60 - the HAT enzyme of the NuA4 complex. We identify here a panel of
      424 genes, referred to as MYC-Tip60 co-regulated panel (MTcoR), that are
      dependent on both MYC and Tip60 for expression and likely co-regulated by MYC and
      the NuA4 complex. The MTcoR panel is most significantly enriched in genes
      involved in cell cycle and/or DNA replication. In contrast, genes repressed by
      shMYC but not by shTip60 (224 genes) have a low significance of enrichment in
      identifiable biological processes other than cell cycle and DNA replication.
      Genes repressed by shTip60 but not by shMYC (102 genes) have no significant
      identifiable gene enrichment. We propose that MYC cooperates with the NuA4
      complex to activate the MTcoR panel of genes to promote DNA replication and cell
      cycle.

PMID- 30108680
TI  - Exosomes derived from cancerous and non-cancerous cells regulate the anti-tumor
      response in the tumor microenvironment.
AB  - The tumor microenvironment (TME) is a unique platform of cancer biology that
      considers the local cellular environment in which a tumor exists. Increasing
      evidence points to the TME as crucial for either promoting immune tumor rejection
      or protecting the tumor. The TME includes surrounding blood vessels, the
      extracellular matrix (ECM), a variety of immune and regulatory cells, and
      signaling factors. Exosomes have emerged to be molecular contributors in cancer
      biology, and to modulate and affect the constituents of the TME. Exosomes are
      small (40-150 nm) membrane vesicles that are derived from an endocytic nature and
      are later excreted by cells. Depending on the cells from which they originate,
      exosomes can play a role in tumor suppression or tumor progression. Tumor-derived
      exosomes (TDEs) have their own unique phenotypic functions. Evidence points to
      TDEs as key players involved in tumor growth, tumorigenesis, angiogenesis,
      dysregulation of immune cells and immune escape, metastasis, and resistance to
      therapies, as well as in promoting anti-tumor response. General exosomes, TDEs,
      and their influence on the TME are an area of promising research that may provide
      potential biomarkers for therapy, potentiation of anti-tumor response,
      development of exosome-based vaccines, and exosome-derived nanocarriers for
      drugs.

PMID- 30108682
TI  - The expression of genes contributing to pancreatic adenocarcinoma progression is
      influenced by the respective environment.
AB  - Pancreatic adenocarcinoma is a highly aggressive malignancy with dismal prognosis
      and limited curative options. We investigated the influence of organ environments
      on gene expression in RNU rats by orthotopic and intraportal infusion of Suit2
      007luc cells into the pancreas, liver and lung respectively. Tumor tissues from
      these sites were analyzed by chip array and histopathology. Generated data was
      analyzed by Chipster and Ingenuity Pathway Analysis (+/-1.5 expression fold
      change and p<0.05). Further analysis of functional annotations derived from IPA,
      was based on selected genes with significant modulation of expression. Comparison
      of groups was performed by creating ratios from the mean expression values
      derived from pancreas and respective in vitro values, whereas those from liver
      and lung were related to pancreas, respectively. Genes of interest from three
      functional annotations for respective organs were identified by exclusion-overlap
      analyses. From the resulting six genes, transglutaminase2 (TGM2) was further
      investigated by various assays. Its knockdown with siRNA induced dose dependent
      inhibitory and stimulatory effects on cell proliferation and cell migration,
      respectively. DNA fragmentation indicated apoptotic cell death in response to
      TGM2 knockdown. Cell cycle analysis by FACS showed that TGM2 knockdown induced
      G1/S blockade. Therefore, TGM2 and its associated genes may be promising
      therapeutic targets.

PMID- 30108683
TI  - Viral tumor antigen expression is no longer required in radiation-resistant
      subpopulation of JCV induced mouse medulloblastoma cells.
AB  - The human neurotropic polyomavirus JC, JC virus (JCV), infects the majority of
      human population during early childhood and establishes a latent/persistent
      infection for the rest of the life. JCV is the etiologic agent of the fatal
      demyelinating disease of the central nervous system, progressive multifocal
      leukoencephalopathy (PML) that is seen primarily in immunocompromised
      individuals. In addition to the PML, JCV has also been shown to transform cells
      in culture systems and cause a variety of tumors in experimental animals.
      Moreover, JCV genomic DNA and tumor antigen expression have been shown in a
      variety of human tumors with CNS origin. Similar to all polyomaviruses, JCV
      encodes for several tumor antigens from a single transcript of early coding
      region via alternative splicing. There is little known regarding the
      characteristics of JCV induced tumors and impact of DNA damage induced by
      radiation on viral tumor antigen expression and growth of these cells. Here we
      analyzed the possible impact of ionizing radiation on transformed phenotype and
      tumor antigen expression by utilizing a mouse medulloblastoma cell line (BSB8)
      obtained from a mouse transgenic for JCV tumor antigens. Our results suggest that
      a small subset of BSB8 cells survives and shows radiation resistance. Further
      analysis of the transformed phenotype of radiation resistant BSB8 cells (BSB8-RR)
      have revealed that they are capable of forming significantly higher numbers and
      sizes of colonies under anchorage dependent and independent conditions with
      reduced viral tumor antigen expression. Moreover, BSB8-RR cells show an increased
      rate of double-strand DNA break repair by homologous recombination (HR). More
      interestingly, knockout studies of JCV tumor antigens by utilizing CRISPR/Cas9
      gene editing reveal that unlike parental BSB8 cells, BSB8-RR cells are no longer
      required the expression of viral tumor antigens in order to maintain transformed
      phenotype.

PMID- 30108684
TI  - Mismatch repair gene mutations lead to lynch syndrome colorectal cancer in rhesus
      macaques.
AB  - Colorectal cancer accounts for a substantial number of deaths each year
      worldwide. Lynch Syndrome is a genetic form of colorectal cancer (CRC) caused by
      inherited mutations in DNA mismatch repair (MMR) genes. Although researchers have
      developed mouse models of Lynch Syndrome through targeted mutagenesis of MMR
      genes, the tumors that result differ in important ways from those in Lynch
      Syndrome patients. We identified 60 cases of CRC in rhesus macaques (Macaca
      mulatta) at our facility since 2001. The tumors occur at the ileocecal junction,
      cecum and proximal colon and display clinicopathologic features similar to human
      Lynch Syndrome. We conducted immunohistochemical analysis of CRC tumors from
      several rhesus macaques, finding they frequently lack expression of MLH1 and PMS2
      proteins, both critical MMR proteins involved in Lynch Syndrome. We also found
      that most macaque cases we tested exhibit microsatellite instability, a defining
      feature of Lynch Syndrome. Whole genome sequencing of rhesus macaque CRC cases
      identified mutations in MLH1 and/or MSH6 that are predicted to disrupt protein
      function. We conclude that this population of rhesus macaques constitutes a
      spontaneous model of Lynch Syndrome, matching the human disease in several
      significant characteristics, including genetic risk factors that parallel human
      Lynch Syndrome.

PMID- 30108685
TI  - FHIRChain: Applying Blockchain to Securely and Scalably Share Clinical Data.
AB  - Secure and scalable data sharing is essential for collaborative clinical decision
      making. Conventional clinical data efforts are often siloed, however, which
      creates barriers to efficient information exchange and impedes effective
      treatment decision made for patients. This paper provides four contributions to
      the study of applying blockchain technology to clinical data sharing in the
      context of technical requirements defined in the "Shared Nationwide
      Interoperability Roadmap" from the Office of the National Coordinator for Health
      Information Technology (ONC). First, we analyze the ONC requirements and their
      implications for blockchain-based systems. Second, we present FHIRChain, which is
      a blockchain-based architecture designed to meet ONC requirements by
      encapsulating the HL7 Fast Healthcare Interoperability Resources (FHIR) standard
      for shared clinical data. Third, we demonstrate a FHIRChain-based decentralized
      app using digital health identities to authenticate participants in a case study
      of collaborative decision making for remote cancer care. Fourth, we highlight key
      lessons learned from our case study.

PMID- 30108687
TI  - Putting chemistry back in biology.
AB  - The chemical nature of biomolecular interactions can no longer be ignored.

PMID- 30108686
TI  - Large extracellular vesicles carry most of the tumour DNA circulating in prostate
      cancer patient plasma.
AB  - Cancer-derived extracellular vesicles (EVs) are membrane-enclosed structures of
      highly variable size. EVs contain a myriad of substances (proteins, lipid, RNA,
      DNA) that provide a reservoir of circulating molecules, thus offering a good
      source of biomarkers. We demonstrate here that large EVs (L-EV) (large oncosomes)
      isolated from prostate cancer (PCa) cells and patient plasma are an EV population
      that is enriched in chromosomal DNA, including large fragments up to 2 million
      base pair long. While L-EVs and small EVs (S-EV) (exosomes) isolated from the
      same cells contained similar amounts of protein, the DNA was more abundant in L
      EV, despite S-EVs being more numerous. Consistent with in vitro observations, the
      abundance of DNA in L-EV obtained from PCa patient plasma was variable but
      frequently high. Conversely, negligible amounts of DNA were present in the S-EVs
      from the same patients. Controlled experimental conditions, with spike-ins of L
      EVs and S-EVs from cancer cells in human plasma from healthy subjects, showed
      that circulating DNA is almost exclusively enclosed in L-EVs. Whole genome
      sequencing revealed that the DNA in L-EVs reflects genetic aberrations of the
      cell of origin, including copy number variations of genes frequently altered in
      metastatic PCa (i.e. MYC, AKT1, PTK2, KLF10 and PTEN). These results demonstrate
      that L-EV-derived DNA reflects the genomic make-up of the tumour of origin. They
      also support the conclusion that L-EVs are the fraction of plasma EVs with DNA
      content that should be interrogated for tumour-derived genomic alterations.

PMID- 30108688
TI  - Antimalarial drug discovery targeting apical membrane antigen 1.
AB  - Malaria continues to frustrate humanity's attempts to eradicate this deadly
      disease. Although gains have been made over the last 15 years, drug resistance to
      malaria continues to be a major concern. The lack of new antimalarials with novel
      mechanisms of action continues to challenge the scientific community to find
      innovative targets to combat this persistent disease. One such target, apical
      membrane antigen 1 (AMA1), is an essential protein that helps the parasite invade
      host erythrocytes. Recently, a number of efforts have focused on the druggability
      of this target, aiming to block the interactions of AMA1 that mediate invasion of
      host cells. This review covers recent progress in drug discovery targeting this
      crucial protein-protein interaction in malaria.

PMID- 30108689
TI  - Hypoxia inducible factor down-regulation, cancer and cancer stem cells (CSCs):
      ongoing success stories.
AB  - In cancers, hypoxia inducible factor 1 (HIF-1) is an over-expressed transcription
      factor, which regulates a large set of genes involved in tumour vascularization,
      metastases, and cancer stem cells (CSCs) formation and self-renewal. This protein
      has been identified as a relevant target in oncology and several HIF-1 modulators
      are now marketed or in advanced clinical trials. The purpose of this review is to
      summarize the advances in the understanding of its regulation and its inhibition,
      from the medicinal chemist point of view. To this end, we selected in the recent
      literature relevant examples of "hit" compounds, including small-sized organic
      molecules, pseudopeptides and nano-drugs, exhibiting in vitro and/or in vivo both
      anti-HIF-1 and anti-tumour activities. Whenever possible, a particular emphasis
      has been dedicated to compounds that selectively target CSCs.

PMID- 30108692
TI  - Development of small molecular compounds targeting cancer stem cells.
AB  - Cancer stem cells (CSCs) are indicated to play critical roles in drug resistance,
      recurrence, and metastasis of cancer. Although molecular targeted therapies have
      contributed to the improvement of cancer treatments by targeting vulnerable
      pathways indispensable to the proliferation and survival of cancer cells, no
      relevant therapeutic modalities targeting CSCs have been developed yet. This
      review focuses on MELK (maternal embryonic leucine zipper kinase), TOPK (T
      lymphokine-activated killer cell-originated protein kinase), and TTK (tyrosine
      threonine kinase), which are over-expressed frequently in human cancers and play
      indispensable roles in the development and maintenance of cancer stem cells. In
      addition, we will discuss recently developed small molecules for these protein
      targets, which have shown remarkable anti-tumor efficacies in several preclinical
      studies.

PMID- 30108691
TI  - Boron-containing delocalised lipophilic cations for the selective targeting of
      cancer cells.
AB  - To limit the incidence of relapse, cancer treatments must not promote the
      emergence of drug resistance in tumour and cancer stem cells. Under the proviso
      that a therapeutic amount of boron is selectively delivered to cancer cells,
      Boron Neutron Capture Therapy (BNCT) may represent one approach that meets this
      requirement. To this end, we report the synthesis and pharmacology of several
      chemical entities, based on boron-rich carborane moieties that are functionalised
      with Delocalized Lipophilic Cations (DLCs), which selectively target the
      mitochondria of tumour cells. The treatment of tumour and cancer stem cells
      (CSCs) with such DLC-functionalized carboranes (DLC-carboranes) induces cell
      growth arrest that is both highly cancer-cell-selective and permanent.
      Experiments involving cultures of normal and cancer cells show that only normal
      cells exhibit recapitulation of their proliferation potential upon removal of the
      DLC-carborane treatment. At the molecular level, the pharmacological effect of
      DLC-carboranes is exerted through activation of the p53/p21 axis.

PMID- 30108693
TI  - Quinoides and VEGFR2 TKIs influence the fate of hepatocellular carcinoma and its
      cancer stem cells.
AB  - Bioactivities of quinoides 1-5 and VEGFR2 TKIs 6-10 in hepatocellular cancer
      (HCC) and cancer stem cells (HCSCs) were studied. The compounds exhibited IC50
      values in MUM concentrations in HCC cells. Quinoide 3 was able to eradicate
      cancer stem cells, similar to the action of the stem cell inhibitor DAPT.
      However, the more cytotoxic VEFGR TKIs (IC50: 0.4-3.0 MUM) including sorafenib,
      which is the only FDA approved drug for the treatment of HCC, enriched the
      hepatocellular cancer stem cell population by 2-3 fold after treatment. An
      aggressiveness factor (AF) was proposed to quantify the characteristics of drug
      candidates for their ability to eradicate the CSC subpopulation. Considering the
      tumour heterogeneity and marker positive cancer stem cell like subpopulation
      enrichment upon treatments in patients, this study emphasises the importance of
      the chemotherapeutic agent choice acting differentially on all the subpopulations
      including marker-positive CSCs.

PMID- 30108694
TI  - Tumor cell resistance against targeted therapeutics: the density of cultured
      glioma tumor cells enhances Stat3 activity and offers protection against the
      tyrosine kinase inhibitor canertinib.
AB  - Tumor cell resistance to drug treatment severely limits the therapeutic success
      of treatment. Tumor cells, exposed to chemotherapeutic drugs, have developed
      intricate strategies to escape the cytotoxic effects and adapt to adverse
      conditions. The molecular mechanisms causing drug resistance can be based upon
      modifications of drug transport or metabolism, structural alterations of drug
      targets or adaptation of cellular signaling. An important component in the
      transformation of cells and the emergence of drug resistance is the activation of
      the transcription factor Stat3. The persistent, inappropriate activation of Stat3
      causes the expression of target genes which promote tumor cell proliferation,
      survival, invasion and immune suppression, and it is instrumental in the process
      of the emergence of resistance to both conventional chemotherapeutic agents and
      novel targeted compounds. For these reasons, Stat3 inhibition is being pursued as
      a promising therapeutic strategy. We have investigated the effects of the
      tyrosine kinase inhibitor canertinib on the glioma cell line Tu-2449. In these
      cells Stat3 is persistently phosphorylated and activated downstream of the
      oncogenic driver v-Src and its effector, the cytoplasmic tyrosine kinase Bmx.
      Canertinib exposure of Tu-2449 cells rapidly caused the inhibition of the Bmx
      kinase and the deactivation of Stat3. Prolonged exposure of the cells to
      canertinib caused the death of the large majority of the cells. Only a few cells
      became resistant to canertinib and survived in tight clusters. These cells have
      become drug resistant. When the canertinib resistant cells were expanded and
      cultured at lower cell densities, they regained their sensitivity towards
      canertinib. We measured the extent of Stat3 activation as a function of cell
      density and found that higher cell densities are accompanied by increased Stat3
      activation and a higher expression of Stat3 target genes. We suggest that Stat3
      induction through tight cell-cell interactions, most likely through the
      engagement of cadherins, can counteract the inhibitory effects exerted by
      canertinib on Bmx. Cell-cell interactions induced Stat3 and compensated for the
      suppression of Stat3 by canertinib, thus transiently protecting the cells from
      the cytotoxic effects of the inhibitor.

PMID- 30108690
TI  - Adaptive mechanisms of resistance to anti-neoplastic agents.
AB  - Intrinsic and acquired resistance to conventional and targeted therapeutics is a
      fundamental reason for treatment failure in many cancer patients. Targeted
      approaches to overcome chemoresistance as well as resistance to targeted
      approaches require in depth understanding of the underlying molecular mechanisms.
      The anti-cancer activity of a drug can be limited by a broad variety of molecular
      events at different levels of drug action in a cell-autonomous and non-cell
      autonomous manner. This review summarizes recent insights into the adaptive
      mechanisms used by tumours to resist therapy including cellular phenotypic
      plasticity, dynamic alterations of the tumour microenvironment, activation of
      redundant signal transduction pathways, modulation of drug target expression
      levels, and exploitation of pro-survival responses.

PMID- 30108695
TI  - (Chalcogen)semicarbazones and their cobalt complexes differentiate HL-60 myeloid
      leukaemia cells and are cytotoxic towards tumor cell lines.
AB  - Cobalt complexes with semi- and thiosemicarbazones of 8-quinolinecarboxaldehyde
      have been synthesized and characterized by X-ray diffraction analysis. These
      novel complexes and a previously synthesized cobalt complex with a selenium-based
      selenosemicarbazone ligand showed myeloid differentiation activity on all trans
      retinoic acid resistant HL-60 acute myeloid leukaemia cells. They also showed
      varying levels of cytotoxicity on five human tumor cell lines: cervix carcinoma
      cells (HeLa), lung adenocarcinoma cells (A549), colorectal adenocarcinoma cells
      (LS-174), breast carcinoma cells (MDA-MB-361), and chronic myeloid leukaemia
      (K562) as well as one normal human cell line: fetal lung fibroblast cells (MRC
      5). Leukaemia differentiation was most strongly induced by a metal-free oxygen
      ligand and the selenium ligand, whilst the latter and the cobalt(ii) complex with
      an oxygen ligand showed the strongest dose-dependent cytotoxic activity. In four
      out of five investigated tumor cell lines, it was of the same order of magnitude
      as cisplatin. These best compounds, however, had lower toxicity on non
      transformed MRC-5 cells than cisplatin.

PMID- 30108696
TI  - Withaferin A induces cell death and differentiation in multiple myeloma cancer
      stem cells.
AB  - Multiple myeloma (MM) remains an incurable malignancy despite the development of
      novel therapeutics. This is believed to be due to a subset of rare chemotherapy
      resistant cancer stem cells (CSCs). Differentiation therapy represents one
      strategy aimed at reducing the stemness of CSCs. The anticancer effect of
      withaferin A (WFA) was studied in MM-CSCs and RPMI 8226 MM tumoral plasma cells
      (RPMIs). WFA exhibited growth inhibitory effects in both MM-CSCs and RPMIs, with
      IC50 values of 649 and 224 nM, respectively. WFA also induced a G2 cell cycle
      arrest, as well as cell death and apoptosis. Although, WFA did not exhibit a
      direct anti-migratory effect, a remarkable morphological change was observed in
      MM-CSCs in response to WFA treatment. Using qPCR gene expression analyses, WFA
      caused a reduction in stemness markers, and a promotion of differentiation
      markers in MM-CSCs. These results warrant further investigation of WFA in
      relevant MM animal models.

PMID- 30108698
TI  - Exploring inhibitor structural features required to engage the 216-loop of human
      parainfluenza virus type-3 hemagglutinin-neuraminidase.
AB  - Human parainfluenza virus type-3 is a leading cause of acute respiratory
      infection in infants and children. There is currently neither vaccine nor
      clinically effective treatment for parainfluenza virus infection. Hemagglutinin
      neuraminidase glycoprotein is a key protein in viral infection, and its
      inhibition has been a target for inhibitor development. In this study, we explore
      the structural features required for Neu2en derivatives to efficiently lock-open
      the 216-loop of the human parainfluenza virus type-3 hemagglutinin-neuraminidase
      protein.

PMID- 30108697
TI  - Evaluation of intoxicating effects of liquor products on drunken mice.
AB  - Consumption of alcoholic beverages increases the risk of human health problems
      such as liver, heart and blood vessel diseases. In the present study, the concept
      of intoxicating degree (ID) is proposed as an index to demonstrate the degree of
      intoxicating activity for consuming liquor products. A mice model was designed
      for the evaluation of liquor product IDs. The intoxicating effects of liquor
      products were investigated by blood alcohol concentrations (BAC) and behaviour
      abilities of mice including righting reflex, running and forced-swim abilities. A
      linear regression model between comprehensive drunkenness degree (CD), calculated
      by integrating BAC and the behaviour abilities, and alcohol-feeding dosages (W),
      was established (with R2 > 0.9) with a slope factor of K. The ratio of the K
      values of liquor products to that of purified alcohol could be used to express
      the ID. For ID values less than 1, the liquor product would have a lower
      intoxicating effect when the same amount of alcohol content was consumed and vice
      versa.

PMID- 30108699
TI  - Synthesis and biological evaluation of memantine nitrates as a potential
      treatment for neurodegenerative diseases.
AB  - A series of memantine nitrate derivatives, as dual functional compounds with
      neuroprotective and vasodilatory activity for neurodegenerative diseases, was
      designed and synthesized. These compounds combined the memantine skeleton and a
      nitrate moiety, and thus inhibited the N-methyl-d-aspartic acid receptor and
      released NO in the central nervous system. The biological evaluation results
      revealed that the new memantine nitrates were effective in protecting neurons
      against glutamate-induced injury in vitro. Moreover, memantine nitrates dilated
      aortic rings against phenylephrine-induced contraction. The structure-activity
      relationships of neuroprotection and vasodilation were both analyzed. In further
      studies, compound MN-05 significantly protected cortical neurons by inhibiting
      Ca2+ influx, reducing free radical production and maintaining the mitochondrial
      membrane potential. Further research on MN-05 is warranted.

PMID- 30108701
TI  - 67Ga-metalloprobes: monitoring the impact of geometrical isomers on accumulation
      profiles in rat cardiomyoblasts and human breast carcinoma cells.
AB  - Geometrically similar monocationic gallium(iii) complexes and their radiolabeled
      SPECT counterparts were obtained from Schiff base precursor ligands using ligand
      exchange reactions to evaluate the impact of cis and trans-isomers on their
      cellular accumulation profiles in rat cardiomyoblasts (H9c2(2-1)) and human
      breast carcinoma (MCF-7neo) cells. 67Ga-metalloprobes comprising trans-phenolates
      showing an overall octahedral geometry and exhibiting uniform spatial
      distribution of positive charges on their molecular surface show steady-state
      accumulation in H9c2(2-1) and MCF-7neo cells, and localize in the mitochondria of
      the cells. Importantly, the surrogate geometrically similar and monocationic
      metalloprobe counterparts possessing the cis arrangement of phenolates do not
      show cellular uptake in H9c2(2-1) and MCF-7neo cells. Exploiting their modest
      fluorescent traits, live cell imaging indicates that trans-isomers of
      metalloprobes localize within the mitochondria of cells following their
      penetration, thereby indicating the excellent correlation of radiotracer data and
      live-cell microscopy results. Overall, these results indicate that the cell
      uptake profiles of metalloprobes within this class are mediated by the spatial
      distribution of charges over their molecular surface and hydrophobicity.

PMID- 30108700
TI  - Synthesis and biological activity evaluation of novel peroxo-bridged derivatives
      as potential anti-hepatitis B virus agents.
AB  - Previous studies have demonstrated that natural steroid compounds containing a
      peroxide bridge exhibited potential anti-hepatitis B virus activity. To continue
      our research, a simple and regioselective methodology, using Eosin Y as a clean
      photosensitized oxidation catalyst, was developed for the synthesis of a peroxide
      bridge in steroids. The method that using Eosin Y as the catalyst was exposed to
      visible light and furbished in high yields, did not involve tedious work-up or
      purification, and avoided using environmentally hazardous solvents. It can be
      regarded as a green protocol. Moreover, a series of cholesterol and beta
      sitosterol derivatives containing a peroxide bridge were synthesized using this
      method and screened for their anti-HBV activity. Among the compounds synthesized
      in this research, 5alpha,8alpha-cyclicobioxygen-6-vinyl-3-oxo-cholesterone (1f,
      3.13 MUg ml-1) had the most potent activity with inhibition rates of 77.45% +/-
      6.01% and 58.73% +/- 8.64% on the secretion of HBsAg and HBeAg antigens,
      respectively, after 8 days. Further acute toxicity test showed that the LD50
      value of compound 1f was 362.46 mg kg-1 after an intraperitoneal injection in
      mice. Moreover, structure-activity relationships of cholesterol and beta
      sitosterol derivatives were briefly discussed.

PMID- 30108702
TI  - Towards the rational design of novel drugs based on solubility,
      partitioning/distribution, biomimetic permeability and biological activity
      exemplified by 1,2,4-thiadiazole derivatives.
AB  - Novel 1,2,4-thiadiazole derivatives as potent neuroprotectors were synthesized
      and identified. Their ability to inhibit the glutamate stimulated Ca2+ uptake was
      investigated. The solubility of thiadiazoles was measured in a buffer solution
      (pH 7.4) at 298 K. The distribution coefficients in 1-octanol/buffer (pH 7.4) and
      1-hexane/buffer (pH 7.4) immiscible phases as model systems imitating the
      gastrointestinal tract epithelium and the blood-brain barrier were determined.
      Permeation experiments the new PermeapadTM barrier using Franz diffusion cells
      were conducted and the apparent permeability coefficients were obtained. The
      influence of the compound structure on the physicochemical properties determining
      the bioavailability of drug-like substances was revealed. Solubility-permeability
      interplay has been assessed to evaluate potential bioavailability of the
      compounds studied.

PMID- 30108703
TI  - Design, synthesis, anticancer activity and docking studies of theophylline
      containing 1,2,3-triazoles with variant amide derivatives.
AB  - A new series of theophylline analogues containing 1,2,3-triazoles with different
      amide groups (22-41) has been designed and synthesized, and their biological
      activities have been evaluated as potential anticancer agents. The anticancer
      activities of the synthesized compounds were studied in four cancer cell lines
      viz. lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375). Furthermore,
      these compounds were screened for computational ADME and Lipinski's analysis
      followed by molecular docking and binding energy calculations against the various
      therapeutic targets involved in cell proliferation. The in vitro results
      demonstrate that compounds 22, 27, 36 and 40 have pivotal anticancer activity.
      Among these, compounds 22 and 27 have significant cytotoxic activity in all three
      cell lines; the in silico docking studies also reveal that compounds 22, 27 and
      36 have good dock scores, binding affinities and binding energies towards human
      epidermal growth factor receptor 2. This is the first report to demonstrate
      theophylline hybrids containing 1,2,3-triazoles as potential anticancer agents.

PMID- 30108705
TI  - Discovery of selective cystathionine beta-synthase inhibitors by high-throughput
      screening with a fluorescent thiol probe.
AB  - A high-throughput assay was developed to identify inhibitors of cystathionine
      beta-synthase (CBS), which is one of three key enzymes involved in H2S
      biosynthesis. Screening of 6491 natural compounds identified several selective
      CBS inhibitors, which suppressed the proliferation of HT29 cancer cells, with
      IC50 values of less than 10 MUM.

PMID- 30108704
TI  - Synthesis, crystal structure, cytotoxicity and action mechanism of a Rh(iii)
      complex with 8-hydroxy-2-methylquinoline as a ligand.
AB  - A rhodium(iii) complex, [Rh(MQ)(DMSO)2Cl2] (1), with 8-hydroxy-2-methylquinoline
      as the ligand was synthesized and characterized. Complex 1 exhibited cytotoxicity
      against BEL-7404, Hep-G2, NCI-H460, T-24, and A549 cell lines with IC50 values in
      the micromolar range (6.52-17.86 MUM). Various experiments on the Hep-G2 cells
      showed that complex 1 caused cell cycle arrest at the S phase, downregulation of
      cdc25 A, cyclin A, cyclin B and CDK2, and upregulation of p21, p27 and p53.
      Furthermore, cytotoxicity mechanism studies suggested that complex 1-induced
      apoptosis was achieved via disruption of the mitochondrial function, which led to
      a significant loss of the mitochondrial membrane potential, an increase in the
      cellular levels of reactive oxygen species, cytochrome c, and apaf-1, and a
      fluctuation of the intracellular Ca2+ concentration. Taken altogether, complex 1
      can trigger cancer cell death by inducing apoptosis through a mitochondrial
      dysfunction pathway.

PMID- 30108706
TI  - Determination and reduction of translocator protein (TSPO) ligand rs6971
      discrimination.
AB  - The 18 kDa translocator protein (TSPO) is a target for development of diagnostic
      imaging agents for glioblastoma and neuroinflammation. Clinical translation of
      TSPO imaging agents has been hindered by the presence of a polymorphism, rs6971,
      which causes a non-conservative substitution of alanine for threonine at amino
      acid residue 147 (TSPO A147T). Disclosed brain-permeant second-generation TSPO
      ligands bind TSPO A147T with reduced affinity compared to the wild type protein
      (TSPO WT). Efforts to develop a TSPO ligand that binds TSPO WT and TSPO A147T
      with similarly high affinity have been hampered by a lack of knowledge about how
      ligand structure differentially influences interaction with the two forms of
      TSPO. To gain insight, we have established human embryonic kidney cell lines
      stably over-expressing human TSPO WT and TSPO A147T, and tested how modifications
      of a novel N-alkylated carbazole scaffold influence affinity to both TSPO
      isoforms. Most of the new analogues developed in this study showed high affinity
      to TSPO WT and a 5-6-fold lower affinity to TSPO A147T. Addition of electron
      withdrawing substituents yielded analogues with highest affinity for TSPO A147T
      without decreasing affinity for TSPO WT. This knowledge can be used to inform
      further development of non-discriminating TSPO ligands for use as diagnostic
      markers for glioblastoma and neuroinflammation irrespective of rs6971.

PMID- 30108707
TI  - T- and B-cell immunosuppressive activity of novel alpha-santonin analogs with
      humoral and cellular immune response in Balb/c mice.
AB  - In continuation of our endeavours to synthesize immunosuppressive agents from
      alpha-santonin, we report herein the design and synthesis of a new series of
      alpha-santonin derived O-aryl/aliphatic ether, ester and amide analogs and the
      evaluation of their immunosuppressive activities. The in vitro studies led to
      several analogs with significant immunosuppressive effects by inhibiting ConA and
      LPS stimulated T- and B-cell proliferation in a dose dependent manner. The more
      significant compounds 4d, 4e, 4f, 4h, 6a and 6b displayed potent inhibitory
      activity on the mitogen-induced T- and B-cell proliferation in comparison to
      alpha-santonin 1. Compound 4e displayed stupendous in vitro immunosuppressive
      effects with ~80% suppression of B and ~75% suppression of T lymphocyte
      proliferation, respectively. The in vivo investigation on BALB/c mice revealed
      that non-cytotoxic compound 4e suppresses both humoral and cellular immunity.

PMID- 30108708
TI  - Design, synthesis and anticonvulsant-analgesic activity of new N-[(phenoxy)alkyl]
      and N-[(phenoxy)ethoxyethyl]aminoalkanols.
AB  - New derivatives of N-[(phenoxy)alkyl]- and N-[(phenoxy)ethoxyethyl]aminoalkanols
      have been synthesized and evaluated for their anticonvulsant activity in maximal
      electroshock (MES), maximal electroshock seizure threshold (MEST), and
      pentylenetetrazol (PTZ) tests. Their neurotoxicity was evaluated via rotarod and
      chimney tests. The compounds exhibiting the most beneficial activity and
      protection indices were evaluated for analgesic activity using the formalin test
      for neurogenic pain. They were also evaluated for their influence on cytotoxic
      activity using in vitro cellular models (HepG2 and CRL-2534 cell lines).
      Experiments performed using MTT and neutral red cytotoxicity assays showed that
      all evaluated compounds were safe for normal, glial cells (astrocytes) and did
      not induce hepatotoxic effects. Based on the results from the in vitro studies,
      the safety of the evaluated compounds was inferred. The most promising compound
      in this research was 1-{2-[2-(2,3-dimethylphenoxy)ethoxy]ethyl}piperidin-3-ol
      hydrochloride. Additionally, in silico metabolism prediction for the compound has
      been performed.

PMID- 30108709
TI  - Design and synthesis of novel selective estrogen receptor degradation inducers
      based on the diphenylheptane skeleton.
AB  - Estrogen receptors (ERs) are a family of nuclear receptors (NRs) that regulate
      physiological effects such as reproduction and bone homeostasis. It has been
      reported that approximately 70% of human breast cancers are hormone-dependent and
      ERalpha-positive. Recently, novel anti-breast cancer drugs based on different
      mechanisms of action have received significant attention. In this article, we
      have designed and synthesized a selective ER degradation inducer based on the
      diphenylheptane skeleton. Western blotting analysis revealed that PBP-NC10
      degraded ERalpha through the ubiquitin-proteasome system. We also performed
      computational docking analysis to predict the binding mode of PBP-NC10 to
      ERalpha.

PMID- 30108710
TI  - Novel lead compounds in pre-clinical development against African sleeping
      sickness.
AB  - Human African trypanosomiasis (HAT), also known as African sleeping sickness, is
      caused by parasitic protozoa of the genus Trypanosoma. As the disease progresses,
      the parasites cross the blood brain barrier and are lethal for the patients if
      the disease is left untreated. Current therapies suffer from several drawbacks
      due to e.g. toxicity of the respective compounds or resistance to approved
      antitrypanosomal drugs. In this review, the different strategies of drug
      development against HAT are considered, namely the target-based approach, the
      phenotypic high throughput screening and the drug repurposing strategy. The most
      promising compounds emerging from these approaches entering an in vivo evaluation
      are mentioned herein. Of note, it may turn out to be difficult to confirm in
      vitro activity in an animal model of infection; however, possible reasons for the
      missing efficacy in unsuccessful in vivo studies are discussed.

PMID- 30108711
TI  - New application of tiplaxtinin as an effective FtsZ-targeting chemotype for an
      antimicrobial study.
AB  - The filamenting temperature-sensitive mutant Z (FtsZ) protein is generally
      recognized as a promising antimicrobial drug target. In the present study, a
      small organic molecule (tiplaxtinin) was identified for the first time as an
      excellent cell division inhibitor by using a cell-based screening approach from a
      library with 250 compounds. Tiplaxtinin possesses potent antibacterial activity
      against Gram-positive pathogens. Both in vitro and in vivo results reveal that
      the compound is able to disrupt dynamic assembly of FtsZ and Z-ring formation
      effectively through the mechanism of stimulating FtsZ polymerization and
      impairing GTPase activity.

PMID- 30108712
TI  - Identification of a potent kinase inhibitor targeting EML4-ALK fusion protein in
      non-small cell lung cancer.
AB  - ALK-fusion proteins play a fundamental role in the development of about 5% of non
      small cell lung cancers. Herein, we identified the compound 5067-0952 as a potent
      ALK inhibitor, which inhibited cell growth, induced apoptosis, and suppressed the
      phosphorylation of ALK, subsequently blocking its downstream signaling pathway.

PMID- 30108713
TI  - Tetrahydroquinolinone derivatives as potent P-glycoprotein inhibitors: design,
      synthesis, biological evaluation and molecular docking analysis.
AB  - P-glycoprotein (P-gp) is a transmembrane efflux pump that has been associated
      with ineffective cancer chemotherapy and multidrug resistance (MDR). Chemical
      inhibitors of P-gp could have potential cancer therapeutic applications by
      preventing or reversing MDR. To exploit this, we designed twenty-five
      tetrahydroquinolinone analogs bearing pyridyl methyl carboxylate at C3 and
      different substituents at C4 as MDR reversal agents. The inhibitory effects of
      the synthesized compounds against P-gp were assessed by flow cytometric
      determination of rhodamine 123 accumulation in P-gp over-expressing MES-SA/DX5
      cells. Fluorescence imaging of intracellular rhodamine 123 accumulation in MES
      SA/DX5 cells was also performed. Furthermore, the effect of active derivatives on
      the reduction of doxorubicin's IC50 in MES-SA/DX5 cells was evaluated using MTT
      assay. Molecular docking was used to confirm the binding mode of some of the
      synthesized compounds. Five compounds in group A, bearing a 2-pyridyl methyl
      ester substituent at the C3 position, significantly increased rhodamine
      accumulation at 25 MUM comparable to verapamil, a well-established P-gp
      inhibitor, while only 2 compounds in group B bearing 3-pyridyl methyl ester at
      the same position had this effect. This study shows that tetrahydroquinolinones
      containing methyl pyridine esters could represent an attractive scaffold for the
      discovery of P-gp inhibitors as MDR reversal agents in cancer cells.

PMID- 30108714
TI  - Mitochondria-targeted betulinic and ursolic acid derivatives: synthesis and
      anticancer activity.
AB  - A series of new betulinic and ursolic acid conjugates with a lipophilic
      triphenylphosphonium cation, meant to enhance the bioavailability and
      mitochondriotropic action of natural triterpenes, have been synthesized. The in
      vitro experiments on three human cancer cell lines (MCF-7, HCT-116 and TET21N)
      revealed that all the obtained triphenylphosphonium triterpene acid derivatives
      not only showed higher cytotoxicity as compared to betulinic acid but were also
      markedly superior in triggering mitochondria-dependent apoptosis, as assessed
      using a range of apoptosis markers such as cytochrome c release, stimulation of
      caspase-3 activity, and cleavage of poly(ADP-ribose) polymerase, which is one of
      the targets of caspase 3. The IC50 was much lower for all triphenylphosphonium
      derivatives when compared to betulinic acid. Out of the tested group of
      conjugates, the most potent toxicity was exhibited by the betulinic acid
      conjugate 9 (for 9, the IC50 values against MCF-7 and TET21N cells were 0.70 MUM
      and 0.74 MUM; for betulinic acid (BA), IC50 > 25 MUM against MCF-7 cells).

PMID- 30108715
TI  - An agent for optical imaging of TrkC-expressing, breast cancer.
AB  - Tropomyosin receptor kinases receptor C is expressed at high levels on the
      surface of tumors from metastatic breast cancer, metastatic melanoma,
      glioblastoma, and neuroblastoma. Previous studies have shown synthetic TrkC
      ligands bearing agents for photodynamic therapy could be used to completely
      ablate 4T1 metastatic breast tumors and suppress metastatic spread in vivo.
      Modification of these probes (A in the text) to make them suitable for near
      infrared optical imaging in vivo would require a substantial increase in
      molecular mass (and hence increased vulnerability to undesirable absorption,
      metabolism and immunogenicity effects), or significant changes to the probe
      design which might compromise binding to TrkC in histochemical studies and on
      live cells. The research featured here was undertaken to investigate if the
      second strategy could be achieved without compromising binding to TrkC-expressing
      tissues. Specifically, an "aza-BODIPY" probe was synthesized to replace a spacer
      fragment in the original probe A. In the event, this new probe design (1a in the
      text) binds TrkC+ breast cancer in live cell cultures, in histochemical studies
      and in an in vivo murine model. Probe 1a binds TrkC+ tissues with good contrast
      with respect to healthy tissues, and much more strongly than an isomeric, non
      TrkC binding, probe (1b) prepared as a negative control.

PMID- 30108716
TI  - Cu(ii) immobilized on Fe3O4@APTMS-DFX nanoparticles: an efficient catalyst for
      the synthesis of 5-substituted 1H-tetrazoles with cytotoxic activity.
AB  - Cu(ii) immobilized on deferasirox loaded amine functionalized magnetic
      nanoparticles (Cu(ii)/Fe3O4@APTMS-DFX) as a novel magnetically recyclable
      heterogeneous catalyst is able to catalyze the [3 + 2] cycloaddition reactions of
      various organic nitriles with sodium azide. Using this method, a series of 5
      substituted-1H-tetrazoles under mild conditions in DMSO were prepared. The
      reaction involves mild reaction conditions with efficient transformation
      capability. The developed catalyst could be easily separated by applying an
      external magnetic field. Furthermore, it could be recycled for 5 runs with
      negligible leaching of copper from the surface of the catalyst. The catalyst was
      characterized by various techniques such as FT-IR, TGA, VSM, SEM-EDX, and ICP
      OES. Several derivatives of 1H-tetrazoles were prepared using this catalyst, and
      their structures were confirmed using different techniques. Then, the synthesized
      anthraquinones were evaluated for their cytotoxicity against several cell lines
      including MCF-7, MAD-MD-231, HT-29, HeLa, neuro-2a and L-929. The results
      obtained from the MTT assay revealed that the 6 derivatives exhibited a high
      level of cytotoxicity. In order to determine the cytotoxicity mechanism, 2
      derivatives with the highest cytotoxic activity were selected, and an apoptosis
      assay was carried out by flow cytometry, which supported that apoptosis is the
      major mechanism.

PMID- 30108717
TI  - Small molecule piperazinyl-benzimidazole antagonists of the gonadotropin
      releasing hormone (GnRH) receptor.
AB  - In this communication, we report the synthesis and characterization of a library
      of small molecule antagonists of the human gonadotropin releasing hormone
      receptor based upon the 2-(4-tert-butylphenyl)-4-piperazinyl-benzimidazole
      scaffold via Cu-catalysed azide alkyne cycloaddition. Our main purpose was to
      find a more soluble compound based on the WAY207024 lead with nanomolar potency
      to inhibit the GnRH receptor. A late stage diversification by the use of click
      chemistry was, furthermore developed to allow for expansion of the library in
      future optimisations. All compounds were tested in a functional assay to
      determine the individual potency of inhibiting stimulation of the receptor by the
      endogenous agonist GnRH. In conclusion, we found that compound 8a showed improved
      solubility compared to WAY207024 and nanomolar affinity to GnRH receptor.

PMID- 30108718
TI  - Encapsulation of nor-beta-lapachone into poly(d,l)-lactide-co-glycolide (PLGA)
      microcapsules: full characterization, computational details and cytotoxic
      activity against human cancer cell lines.
AB  - In this work, we characterize nor-beta-lapachone-loaded (NbetaL-loaded)
      microcapsules prepared using an emulsification/solvent extraction technique.
      Features such as surface morphology, particle size distribution, zeta potential,
      optical absorption, Raman and Fourier transform infrared spectra, thermal
      analysis data, drug encapsulation efficiency, drug release kinetics and in vitro
      cytotoxicity were studied. Spherical microcapsules with a size of 1.03 +/- 0.46
      MUm were produced with an encapsulation efficiency of approximately 19%. Quantum
      DFT calculations were also performed to estimate typical interaction energies
      between a single nor-beta-lapachone molecule and the surface of the
      microparticles. The NbetaL-loaded PLGA microcapsules exhibited a pronounced
      initial burst release. After the in vitro treatment with NbetaL-loaded
      microcapsules, a clear phagocytosis of the spheres was observed in a few minutes.
      The cytotoxic activity against a set of cancer cell lines was investigated.

PMID- 30108719
TI  - Development of highly active anti-Pneumocystis bisbenzamidines: insight into the
      influence of selected substituents on the in vitro activity.
AB  - Here we describe the potency of 21 pentamidine analogues against the fungal
      pathogen, Pneumocystis carinii, in an ATP bioluminescent assay with toxicity
      profiles in 2 mammalian cell lines. Reduction of two 5-methyl-1,2,4-oxadiazole
      rings was applied to the synthesis of acid-labile bisamidines. Anti-Pneumocystis
      activity is discussed in the context of 3 groups of compounds depending on the
      main structural changes of the pentamidine lead structure. The groups include: 1)
      1,4-bis(methylene)piperazine derivatives 1-5; 2) alkanediamide derivatives 6-10;
      3) alkane-derived bisbenzamidines 11-21. IC50 values of 18 compounds were lower
      than the IC50 of pentamidine. Four bisamidines were active at nanogram
      concentrations. Introduction of sulfur atoms in the alkane bridge, replacement of
      the amidino groups with imidazoline rings, or attachment of nitro or amino groups
      to the benzene rings is responsible for remarkable activity of the new leading
      structures. The vast majority of compounds, including four highly active ones,
      can be classified as mild or nontoxic to host cells. These compounds show promise
      as candidates for new anti-Pneumocystis agents.

PMID- 30108721
TI  - Orthoester functionalized N-guanidino derivatives of 1,5-dideoxy-1,5-imino-d
      xylitol as pH-responsive inhibitors of beta-glucocerebrosidase.
AB  - Alkylated guanidino derivatives of 1,5-dideoxy-1,5-imino-d-xylitol bearing an
      orthoester moiety were prepared using a concise synthetic protocol. Inhibition
      assays with a panel of glycosidases revealed that one of the compounds prepared
      displays potent inhibition against human beta-glucocerebrosidase (GBA) at pH 7.0
      with IC50 values in the low nanomolar range. Notably, a significant drop in
      inhibitory activity is observed when the same compound is tested at pH 5.2. This
      pH sensitive activity is due to degradation of the orthoester functionality at
      lower pH accompanied by loss of the alkyl group. This approach provides a degree
      of control in tuning enzyme inhibition based on the local pH. Compounds like
      those here described may serve as tools for studying various lysosomal storage
      disorders such as Gaucher disease. In this regard, the most active compound was
      also evaluated as a potential pharmacological chaperone by assessing its effect
      on GBA activity in an assay employing fibroblasts from Gaucher patients.

PMID- 30108720
TI  - Benzisoxazole: a privileged scaffold for medicinal chemistry.
AB  - The benzisoxazole analogs represent one of the privileged structures in medicinal
      chemistry and there has been an increasing number of studies on benzisoxazole
      containing compounds. The unique benzisoxazole scaffold also exhibits an
      impressive potential as antimicrobial, anticancer, anti-inflammatory, anti
      glycation agents and so on. This review examines the state of the art in
      medicinal chemistry as it relates to the comprehensive and general summary of the
      different benzisoxazole analogs, their use as starting building blocks of
      multifarious architectures on scales sufficient to drive human drug trials. The
      number of reports describing benzisoxazole-containing highly active compounds
      leads to the expectation that this scaffold will further emerge as a potential
      candidate in the field of drug discovery.

PMID- 30108722
TI  - Cancer nanomedicine: from PDGF targeted drug delivery.
AB  - An innovative approach for the distinctively efficient action of smart targeted
      drug delivery to a specific cell type is obtained through the modification of the
      surface of nanoparticles. Specifically, the work identifies a cell surface
      receptor targeting drug delivery nanosystem based on mesoporous silica loaded
      with the anticancer drug cisplatin (cis-DDP) and poly-acrylic acid (PAA). A
      specific target is the PDGF receptors expressed in cervical cancer cells, thus
      making the PAA functionalized nanocomposite a suitable and promising nano
      medicine for the targeting of PDGF-overexpressing cancers in the near future.

PMID- 30108723
TI  - Synergism of fused bicyclic 2-aminothiazolyl compounds with polymyxin B against
      Klebsiella pneumoniae.
AB  - A series of fused bicyclic 2-aminothiazolyl compounds were synthesized and
      evaluated for their synergistic effects with polymyxin B (PB) against Klebsiella
      pneumoniae (SIPI-KPN-1712). Some of the synthesized compounds exhibited
      synergistic activity. When 4 MUg ml-1 compound B1 was combined with PB, it showed
      potent antibacterial activity, achieving 64-fold reduction of the MIC of PB.
      Furthermore, compound B1 showed prominent synergistic efficacy in both
      concentration gradient and time-kill curves in vitro. In addition, B1 combined
      with PB also exhibited synergistic and partial synergistic effect against E. coli
      (ATCC25922 and its clinical isolates), Acinetobacter baumannii (ATCC19606 and its
      clinical isolates), and Pseudomonas aeruginosa (Pae-1399).

PMID- 30108724
TI  - The use of matched molecular series networks for cross target structure activity
      relationship translation and potency prediction.
AB  - Matched molecular series (MMS) analysis is an extension of matched molecular pair
      (MMP) analysis where all of the MMPs belong to the same chemical series. An MMS
      within a biological assay is able to capture specific structure activity
      relationships resulting from chemical substitution at a single location in the
      molecule. Under this convention, an MMS has the ability to capture one specific
      interaction vector between the compounds in a series and their therapeutic
      target. MMS analysis has the potential to translate the SAR from one series to
      another even across different protein targets or assays. A significant limitation
      of this approach is the lack of chemical series with a sufficient number of
      overlapping fragments to establish a statistically strong SAR in most databases.
      This results in either an inability to perform MMS analysis altogether or a
      potentially high proportion of spurious matches from chance correlations when the
      MMS compound count is low. This paper presents the novel concept of an MMS
      Network, which captures the SAR relationships between a set of related MMSs and
      significantly enhances the performance of MMS analysis by reducing the number of
      spurious matches leading to the identification of unexpected and potentially
      transferable SAR across assays. The results of a full retrospective leave-one-out
      analysis and randomization simulation are provided, and examples of
      pharmaceutically relevant programs will be presented to demonstrate the potential
      of this method.

PMID- 30108727
TI  - Dark chemical matter in public screening assays and derivation of target
      hypotheses.
AB  - Compounds that are consistently inactive in many screening assays, so-called dark
      chemical matter (DCM), have recently experienced increasing attention. One of the
      reasons is that many DCM compounds may not be fully inert biologically, but may
      provide interesting leads for obtaining compounds that are highly selective or
      active against unusual targets. In this study, we have systematically identified
      DCM among extensively assayed screening compounds and searched for analogs of
      these compounds that have known bioactivities. Analog series containing DCM and
      known bioactive compounds were generated on a large scale, making it possible to
      derive target hypotheses for more than 8000 extensively assayed DCM molecules.

PMID- 30108726
TI  - Triazolopyrimidines identified as reversible myeloperoxidase inhibitors.
AB  - Myeloperoxidase, a mammalian peroxidase involved in the immune system as an anti
      microbial first responder, can produce hypochlorous acid in response to invading
      pathogens. Myeloperoxidase has been implicated in several chronic pathological
      diseases due to the chronic production of hypochlorous acid, as well as other
      reactive radical species. A high throughput screen and triaging protocol was
      developed to identify a reversible inhibitor of myeloperoxidase toward the
      potential treatment of chronic diseases such as atherosclerosis. The
      identification and characterization of a reversible myeloperoxidase inhibitor, 7
      (benzyloxy)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine is described.

PMID- 30108725
TI  - Study on the interaction between the 1,4,5,8-naphthalene diimide-spermine
      conjugate (NDIS) and DNA using a spectroscopic approach and molecular docking.
AB  - The interaction of herring sperm DNA with the 1,4,5,8-naphthalene diimide
      spermine conjugate (NDIS) was studied by UV/vis absorption, fluorescence and CD
      spectroscopic methods. Compared with the 1,8-naphthalimide-spermidine conjugate
      (NIS), the values of KSV (quenching constant) and Kb (binding constant) of NDIS
      were larger, and the hypochromic effect in the UV/vis spectra and the quenching
      effect in the fluorescence of NDIS were more significant. The interaction mode
      between NDIS and DNA was mainly groove binding. The fluorescence experiments at
      varying temperatures showed that the binding process of NDIS and DNA was static,
      as both hydrogen bonds and hydrophobic forces played a major role in the binding
      of NDIS and DNA. The CD spectrum indicated that NDIS caused a conformational
      change, like the B to A-DNA transition, and the tests using KI and NaCl and 1H
      NMR spectroscopy indicated that NDIS was not a classical DNA inserter. All the
      results demonstrated that both the polyamine side chain and the aromatic rings
      affect the process of NDIS binding to DNA, which is thus obviously different from
      that of NIS. The conclusion was confirmed by the in silico molecular docking
      experiments.

PMID- 30108728
TI  - Antiproliferative activities of alkaloid-like compounds.
AB  - Tricyclic alkaloid-like compounds were synthesised in a few steps, via the
      bridging Ritter reaction. The compounds were evaluated for their
      antiproliferative activity against the MCF-7 and the aggressive MDA-MB-231 breast
      cancer cells. The anti-cancer activities of 2c were found to be selective towards
      the aggressive and more challenging to treat triple negative (MDA-MB-231) cell
      line while exhibiting no antiproliferative activities towards the MCF-7 cells at
      the highest concentration tested (50 MUM). The IC50 of compound 2c was determined
      to be 7.9 MUM for the MDA-MB-231 cell line. Furthermore, 2c arrested cell cycle
      at the G2/M phase and induced apoptosis in a dose-dependent manner. Besides in
      house anti-cancer screening, compound 3 was selected for anti-cancer screening by
      the National Cancer Institute and was found to have broad anti-cancer activity
      with selectivity against particular leukaemia, colon, melanoma, and breast cancer
      cell lines. Cytotoxicities of compounds 2c and 3 were also tested against
      noncancerous mammalian cells (VERO cell line), and found to be selective towards
      cancerous cells. The facile synthetic route, unique chemical structures and the
      biological data make these alkaloid-like compounds worthwhile lead compounds for
      further anti-cancer drug development.

PMID- 30108730
TI  - Cu(ii), Ga(iii) and In(iii) complexes of 2-acetylpyridine N(4)
      phenylthiosemicarbazone: synthesis, spectral characterization and biological
      activities.
AB  - In this paper, synthesis and characterization of metal complexes [Cu2(L)3]ClO4
      (1), [Ga(L)2]NO3.2H2O (2) and [In(L)2]NO3.H2O (3) (HL = 2-acetylpyridine N(4)
      phenylthiosemicarbazone) was carried out, including elemental analysis, spectral
      analysis (IR, UV-vis, NMR), and X-ray crystallography. Complex 1 contains one S
      bridged binuclear [Cu2(L)3]+ unit, where two Cu atoms display diverse
      coordination geometries: one being square planar geometry and the other
      octahedral geometry. Both 2 and 3 are mononuclear complexes, and the metal
      centers in 2 and 3 are chelated by two NNS tridentate ligands possessing a
      distorted octahedral geometry. Biological studies show that all the complexes
      possess a wide spectrum of modest to effective antibacterial activities and
      remarkable cytotoxicities against HepG2 cells, and 1, in particular, with an IC50
      value of 0.19 +/- 0.06 MUM, is 113-fold and 28-fold more cytotoxic than HL and
      the antitumor drug mitoxantrone, respectively. In addition, 3 exhibits excellent
      photoluminescence properties. Upon the addition of 1 equiv of In3+ ions, a
      remarkable fluorescence intensity of HL and fluorescent color change (from
      transparent to light-green) could be observed with 365 nm light, indicating that
      this ligand may be used as a promising colorimetric and fluorescent probe for
      In3+ detection.

PMID- 30108729
TI  - Alkyne-azide cycloaddition analogues of dehydrozingerone as potential anti
      prostate cancer inhibitors via the PI3K/Akt/NF-kB pathway.
AB  - Herein, we report the isolation and synthetic modification of dehydrozingerone
      (DHZ, 1), a secondary metabolite present in the rhizome of Zingiber officinale.
      We synthesized O-propargylated dehydrozingerone, which was subsequently coupled
      by alkyne-azide cycloaddition (3-20) using click chemistry. The compounds (1-20)
      were evaluated for their in vitro cytotoxic activity in a panel of three cancer
      cell lines. Among all the DHZ derivatives, 3, 6, 7, 8, 9 and 15 displayed potent
      cytotoxic potential with an IC50 value ranging from 1.8-3.0 MUM in MCF-7, PC-3
      and HCT-116 cell lines. Furthermore, compound 7 has proven to be the most potent
      cytotoxic compound in all the three distinct cancer cell lines and also
      demonstrated significant anti-invasive potential in prostate cancer. The
      mechanistic study of compound 7 showed that it not only suppressed the AKT/mTOR
      signalling which regulates nuclear transcription factor-NF-kB but also augmented
      the expression of anti-invasive markers E-cadherin and TIMP. Compound 7
      significantly decreased the expression of pro-invasive markers vimentin, MMP-2
      and MMP-9, respectively. This study underscores an efficient synthetic approach
      employed to evaluate the structure-activity relationship of dehydrozingerone (1)
      in search of potential new anticancer agents.

PMID- 30108731
TI  - The synthesis, biological evaluation and structure-activity relationship of 2
      phenylaminomethylene-cyclohexane-1,3-diones as specific anti-tuberculosis agents.
AB  - The present study utilised whole cell based phenotypic screening of thousands of
      diverse small molecules against Mycobacterium tuberculosis H37Rv (M.
      tuberculosis) and identified the cyclohexane-1,3-dione-based structures 5 and 6
      as hits. The selected hit molecules were used for further synthesis and a library
      of 37 compounds under four families was synthesized for lead generation.
      Evaluation of the library against M. tuberculosis lead to the identification of
      three lead antituberculosis agents (37, 39 and 41). The most potential compound,
      2-(((2-hydroxyphenyl)amino)methylene)-5,5-dimethylcyclohexane-1,3-dione (39)
      showed an MIC of 2.5 MUg mL-1, which falls in the range of MICs values found for
      the known antituberculosis drugs ethambutol, streptomycin and levofloxacin.
      Additionally, this compound proved to be non-toxic (<20% inhibition at 50 MUM
      concentration) against four human cell lines. Like first line antituberculosis
      drugs (isoniazid, rifampicin and pyrazinamide) this compound lacks activity
      against general Gram positive and Gram negative bacteria and even against M.
      smegmatis; thereby reflecting its highly specific antituberculosis activity.

PMID- 30108732
TI  - New N-(2-phenyl-4-oxo-1,3-thiazolidin-3-yl)-1,2-benzothiazole-3-carboxamides and
      acetamides as antimicrobial agents.
AB  - A series of 21 novel N-[2-phenyl-4-oxo-1,3-thiazolidin-3-yl]-1,2-benzothiazole-3
      carboxamides/acetamides (4a-4p) as well as a series of N'-(halophenylmethylidene)
      1,2-benzothiazole-3-acetohydrazides (3h-3p) have been synthesized and evaluated
      for their antimicrobial activity against eight bacterial and eight fungal
      species, among them plant, animal and human pathogens and food contaminating
      species. All compounds appeared to be potent and the best activity was exhibited
      by compound 4d with MIC in the range of 10.7-21.4 MUmol mL-1 * 10-2 and MBC of
      21.4-40.2 MUmol mL-1 * 10-2. The best antifungal activity was observed for
      compounds 4p and 3h. Elucidation of the relationship between the antimicrobial
      activity and molecular properties of the synthesized compounds was also
      performed. Synthetic intermediates were also tested with several exhibiting good
      antimicrobial activities. Docking studies for some compounds were performed.

PMID- 30108733
TI  - Development of NMR and thermal shift assays for the evaluation of Mycobacterium
      tuberculosis isocitrate lyase inhibitors.
AB  - The enzymes isocitrate lyase (ICL) isoforms 1 and 2 are essential for
      Mycobacterium tuberculosis survival within macrophages during latent tuberculosis
      (TB). As such, ICLs are attractive therapeutic targets for the treatment of
      tuberculosis. However, there are few biophysical assays that are available for
      accurate kinetic and inhibition studies of ICL in vitro. Herein we report the
      development of a combined NMR spectroscopy and thermal shift assay to study ICL
      inhibitors for both screening and inhibition constant (IC50) measurement.
      Operating this new assay in tandem with virtual high-throughput screening has led
      to the discovery of several new ICL1 inhibitors.

PMID- 30108734
TI  - Thiosemicarbazone-based selective proliferation inactivators inhibit gastric
      cancer cell growth, invasion, and migration.
AB  - A series of novel thiosemicarbazone derivatives were synthesized and evaluated
      for their antiproliferative activity against several selected tumor cell lines of
      different origins using the MTT assay. The preliminary results indicated that the
      MGC-803 cell line was remarkably sensitive to all the synthesized compounds.
      Among this series, compound 5n showed the best inhibitory activity with an IC50
      value of 0.93 MUM (about 10-fold more potent than 3-AP) against MGC-803. Further
      mechanism studies revealed that compound 5n could obviously inhibit the
      proliferation of MGC-803 cells by inducing apoptosis and arresting the cell cycle
      at the S phase. Compound 5n also showed marked inhibition of cell migration and
      invasion, without significant cytotoxicity against gastric epithelial
      immortalized GES-1 cells.

PMID- 30108735
TI  - Novel T-C@AgNPs mediated biocidal mechanism against biofilm associated
      methicillin-resistant Staphylococcus aureus (Bap-MRSA) 090, cytotoxicity and its
      molecular docking studies.
AB  - Staphylococcus aureus is a commonly found pathogen that can cause food-spoilage
      and life threatening infections. However, the potential molecular effects of
      natural active thymol molecules and chitosan silver nanoparticles (C@AgNPs) in
      bacteria remain unclear. This gap in the literature has prompted us to study the
      effects of thymol loaded chitosan silver nanoparticles (T-C@AgNPs) against
      biofilm associated proteins in methicillin-resistant S. aureus (Bap-MRSA) 090 and
      also their toxicity, anti-cancer activity, and validation of their in silico
      molecular docking. The results showed excellent antibacterial activity of T
      C@AgNPs against Bap-MRSA 090, having a minimum inhibitory concentration of 100
      MUg mL-1 and a 10.08 +/- 0.06 mm zone of inhibition (ZOI). The cyclic
      voltammogram (CV) analysis clearly showed pore forming of T-C@AgNPs at 300 MUg mL
      1 concentration, and evidence of the interruption of the electron transport chain
      was clearly seen. The 200 MUg mL-1 concentration exhibited a 52.60 +/- 0.25% anti
      biofilm property by T-C@AgNPs against Bap-MRSA 090. The T-C@AgNPs showed no
      toxicity to peripheral blood mononuclear cells (PBMC) (IC50 = 221 +/- 0.71 MUg mL
      1) compared to the control, and anti-cancer activity against human triple
      negative breast cancer cell line (MDA-MB-231) (IC50 110 +/- 1.0 MUg mL-1)
      compared to the standard drug Doxorubicin (IC50 = 19 +/- 1.0). The excellent
      properties of T-C@AgNPs were validated by in silico molecular docking studies and
      showed best match scoring to target proteins compared to standards. These
      excellent properties of T-C@AgNPs highlight for the first time its pharmacology
      and potential in medicinal drug development applications for future research.

PMID- 30108737
TI  - Bioimaging of multiple piRNAs in a single breast cancer cell using molecular
      beacons.
AB  - Simultaneous bioimaging of piR-36026 and piR-36743 using molecular beacons
      successfully visualized 4 different subtypes of breast cancer.

PMID- 30108736
TI  - Synergistic antifungal effect of cyclized chalcone derivatives and fluconazole
      against Candida albicans.
AB  - The occurrence of invasive fungal diseases, particularly in immunocompromised
      patients, is life-threatening and increases the economic burden. The rising
      problem of multi-drug resistance is becoming a major concern for clinicians. In
      addition, a repertoire of antifungal agents is far less in number than
      antibacterial drugs. To combat these problems, combination therapy has gained a
      lot of interest. We previously reported the synergistic interaction of some mono-
      and bis-dihydropyrimidinone and thione derivatives with fluconazole and
      amphotericin B for combination antifungal therapy. In this study we used the same
      approach and synthesized different azole and non-azole derivatives of mono-(M)
      and bis-(B) chalcones and evaluated their antifungal activity profile alone and
      in combination with the most commonly used antifungal drug - fluconazole (FLC) -
      against seven FLC susceptible and three FLC resistant clinically isolated Candida
      albicans strains. Based on the minimum inhibitory concentration results, the bis
      derivatives showed lower MIC values compared to their mono-analogues. Both
      fractional inhibitory concentration index and isobologram results revealed mostly
      synergistic, additive or indifferent interactions between the tested compounds
      and FLC against different Candida isolates. None of the tested compounds showed
      any effect on energy dependent R6G efflux, revealing that they do not reverse the
      mechanism of drug efflux. However, surprisingly, these compounds profoundly
      decreased ergosterol biosynthesis and showed down regulation of ERG11 gene
      expression, which is the possible mechanism of reversal of azole drug resistance
      by these compounds. These results provide a platform for further research to
      develop pyrimidinone/thione ring containing compounds as promising new antifungal
      agents, which could be used in antifungal combination therapy.

PMID- 30108738
TI  - N-Heterocyclic borneol derivatives as inhibitors of Marburg virus glycoprotein
      mediated VSIV pseudotype entry.
AB  - There is currently no approved antiviral therapy for treatment of Marburg virus
      disease (MVD). Although filovirus infection outbreaks are quite rare, the high
      mortality rates in such outbreaks make the development of anti-filoviral drugs an
      important goal of medical chemistry and virology. Here, we performed screening of
      a large library of natural derivatives for their virus entry inhibition activity
      using pseudotype systems. The bornyl ester derivatives containing saturated N
      heterocycles exhibited the highest antiviral activity. It is supposed that
      compounds with specific inhibitory activity toward MarV-GP-dependent virus entry
      will inhibit the rVSIV-DeltaG-MarV-GP pseudotype much more efficiently than the
      control rVSIV-DeltaG-G pseudotype. At the same time, the compounds similarly
      inhibiting both pseudotypes will likely affect rVSIV capsid replication or the
      cellular mechanisms common to the entry of both viruses. Borneol itself is not
      active against both pseudotypes and is nontoxic, whereas its derivatives have
      varying toxicity and antiviral activity. Among low-toxic borneol derivatives, six
      compounds turned out to be relatively specific inhibitors of MarV-GP-mediated
      infection (SC > 10). Of them, compound 6 containing a methylpiperidine moiety
      exhibited the highest virus-specific activity. Notably, the virus-specific
      activity of this compound is twice as high as that of the reference.

PMID- 30108739
TI  - Identification of novel N-acetylcysteine derivatives for the treatment of
      hepatocellular injury.
AB  - New anti-hepatocellular injury drugs with better curative effects and fewer side
      effects are urgently needed at present. In this study, a series of novel N
      acetylcysteine (NAC) derivatives were designed, synthesized and biologically
      evaluated for their anti-hepatocellular injury activities against two different
      cell models. In the biological evaluation against hydrogen peroxide (H2O2)
      induced LO2 hepatocytes, half of the target compounds exhibited moderate to
      potent activities in improving the model cell viability, and two compounds (6a
      and 6b) displayed more potent activities in decreasing malondialdehyde (MDA)
      levels than the positive control NAC. In further 4-acetamidophenol (APAP)-induced
      LO2 cell experiment, compounds 6a and 6b could not only improve the cell
      viability but also significantly reduce the secretion of MDA. Additionally,
      compound 6a displayed excellent Caco-2 permeability and oral bioavailability in
      rats. All these experimental results suggested that compounds 6a and 6b could
      serve as potential lead molecules for further development of anti-hepatocellular
      injury drugs.

PMID- 30108740
TI  - Deciphering the role of hydrophobic and hydrophilic bile acids in angiogenesis
      using in vitro and in vivo model systems.
AB  - Bile acids have emerged as strong signaling molecules capable of influencing
      various biological processes like inflammation, apoptosis, cancer progression and
      atherosclerosis depending on their chemistry. In the present study, we
      investigated the effect of major hydrophobic bile acids lithocholic acid (LCA)
      and deoxycholic acid (DCA) and hydrophilic bile acids cholic acid (CA) and
      chenodeoxycholic acid (CDCA) on angiogenesis. We employed human umbilical vein
      endothelial cells (HUVECs) and zebrafish embryos as model systems for studying
      the role of bile acids in angiogenesis. Our studies revealed that the hydrophilic
      CDCA enhanced ectopic vessel formation as observed by the increase in the number
      of sub-intestinal vessels (SIVs) in the zebrafish embryos. The pro-angiogenic
      role of CDCA was further corroborated by in vitro vessel formation studies
      performed with human umbilical vein endothelial cells (HUVECs), whereas the
      hydrophobic LCA reduced tubulogenesis and was toxic to the zebrafish embryos. We
      validated that CDCA enhances angiogenesis by increasing the expression of
      vascular growth factor receptors (VEGFR1 and VEGFR2) and matrix
      metalloproteinases (MMP9) and by decreasing the expression of adhesion protein
      vascular endothelial cadherin (VE-cadherin). Our work implicates that the nature
      of bile acids plays a critical role in dictating their biological functions and
      in regulating angiogenesis.

PMID- 30108741
TI  - Synthesis and antifungal activity of novel oxazolidin-2-one-linked 1,2,3-triazole
      derivatives.
AB  - Novel oxazolidin-2-one-linked 1,2,3-triazole derivatives (4a-k) were synthesized
      by straightforward and versatile azide-enolate (3 + 2) cycloaddition. The series
      of compounds was screened for antifungal activity against four filamentous fungi
      as well as six yeast species of Candida spp. According to their efficiency and
      breadth of scope, they can be ordered as 4k > 4d > 4h > 4a, especially in
      relation to the activity displayed against Candida glabrata ATCC-34138,
      Trichosporon cutaneum ATCC-28592 and Mucor hiemalis ATCC-8690, i.e. compounds 4d,
      4h and 4k showed excellent activity against C. glabrata (MIC 0.12, 0.25 and 0.12
      MUg mL-1, respectively), better than that of itraconazole (MIC 1 MUg ml-1). The
      activity of compound 4d (MIC = 2 MUg mL-1) was higher than that observed for the
      standard antifungal drug (MIC = 8 MUg mL-1) against Trichosporon cutaneum, while
      compound 4k displayed an excellent antimycotic activity against Mucor hiemalis
      (MIC = 2 MUg mL-1vs. 4 MUg mL-1 for itraconazole). In addition, we describe
      herein a novel mild and eco-friendly synthetic protocol for obtaining beta
      ketosulfones (adducts to afford compounds 4a-k) from alpha-brominated carbonyls
      in an aqueous nanomicellar medium at room temperature.

PMID- 30108742
TI  - Recent advancements in the discovery of protein-protein interaction inhibitors of
      replication protein A.
AB  - Due to the relatively high rate of DNA damage that can occur during cell cycle
      progression, the DNA damage response (DDR) pathway is critical for the survival
      of eukaryotic cells. Replication protein A (RPA) is an essential cell cycle
      checkpoint protein that mediates the initiation of the DDR by binding to single
      stranded DNA (ssDNA) and recruiting response partners via protein-protein
      interactions (PPIs). This important role of RPA in initiating the DDR and cell
      survival has led to interest within the scientific community to investigate RPA
      as a potential cancer drug discovery target. To this end, RPA inhibitors have
      been explored via a variety of methods. This review summarizes the structure and
      function of RPA and highlights recent efforts to discover inhibitors of RPA
      protein interactions.

PMID- 30108743
TI  - Targeting Twist expression with small molecules.
AB  - Twist, as one of the important embryonic transcription factors, regulates
      epithelial-mesenchymal transition (EMT) and migration in embryo formation and
      cancer development. Both Twist-1 and Twist-2 are rarely detectable in healthy
      adult tissues, but are frequently overexpressed in multiple kinds of human cancer
      tissues, such as breast, prostate, uterus, liver, melanoma, etc. Twist is
      considered as a crucial EMT inductor and correlated with carcinoma aggression,
      invasion and metastasis. In the past decades, in-depth investigation has been
      reported in terms of the role of Twist in cancers; in addition, several kinds of
      small molecules have played important roles in studying the effect of Twist on
      cancer development, suggesting that Twist can be regarded as one of the important
      potential targets for cancer treatment. Hence we provide a brief overview of
      Twist and several small molecules targeting its expression, highlighting the
      biological features that make it a charming target for cancer therapy.

PMID- 30108744
TI  - Structural features of many circular and leaderless bacteriocins are similar to
      those in saposins and saposin-like peptides.
AB  - Bacteriocins are potent antimicrobial peptides that are ribosomally produced and
      exported by bacteria, presumably to aid elimination of competing microorganisms.
      Many circular and linear leaderless bacteriocins have a recuring three
      dimensional structural motif known as a saposin-like fold. Although these
      bacteriocin sizes and sequences are often quite different, and their mechanisms
      of action vary, this conserved motif of multiple helices appears critical for
      activity and may enable peptide-lipid and peptide-receptor interactions in target
      bacterial cell membranes. Comparisons between electrostatic surfaces and
      hydrophobic surface maps of different bacteriocins are discussed emphasizing
      similarities and differences in the context of proposed modes of action.

PMID- 30108745
TI  - Small molecules inhibiting Keap1-Nrf2 protein-protein interactions: a novel
      approach to activate Nrf2 function.
AB  - Oxidative stress is well recognized to contribute to the cause of a wide range of
      diseases, such as cancer, diabetes, Alzheimer's disease, arteriosclerosis, and
      inflammation. The Keap1-Nrf2-ARE pathway plays a critical regulatory role and can
      protect cells from oxidative stress through activating Nrf2 to induce its
      downstream phase II enzymes. Nrf2 activation through the covalent inactivation of
      Keap1 may cause unpredictable side effects. Non-covalent disruption of the Keap1
      Nrf2 protein-protein interactions is an alternative strategy for Nrf2 activation,
      potentially with reduced risk of toxicity. Efforts have been made in recent years
      to develop peptide- and small molecule-based Keap1-Nrf2 PPI inhibitors via
      different approaches, including high-throughput screening, target-based virtual
      screening, structure-based optimization, and fragment-based drug design. This
      review aims to highlight the recently discovered small-molecule inhibitors as
      well as their therapeutic potential.

PMID- 30108747
TI  - Novel bivalent securinine mimetics as topoisomerase I inhibitors.
AB  - A series of novel bivalent securinine mimetics incorporating different linkers
      between C-15 and C-15' were synthesized and their topoisomerase I (Topo I)
      inhibitory activities evaluated. It was thus revealed that mimetic R2
      incorporating a rigid m-substituted benzene linker exhibits Topo I inhibitory
      activity three times that of parent securinine. Comprehensive structure-activity
      relationship analyses in combination with docking studies were used to
      rationalize the potent activity of these bivalent mimetics. Mechanistic studies
      served to confirm the deductions arising from docking studies that the active
      bivalent mimetics not only inhibited complexation between Topo I and DNA but also
      stabilized the Topo I-DNA complex itself.

PMID- 30108749
TI  - Development of new scaffolds as reversible tissue transglutaminase inhibitors,
      with improved potency or resistance to glutathione addition.
AB  - Previous studies within our group have yielded a class of cinnamoyl-based
      competitive reversible inhibitors for tissue transglutaminase (TG2), with Ki
      values as low as 1.0 MUM (compound CP4d). However, due to the electrophilic
      nature of their alkene moiety, this class of inhibitors is susceptible to
      nucleophilic attack by glutathione, a key element in cellular metabolism and
      toxicity response. To address this issue, we made several modifications to the
      inhibitor scaffold, ultimately showing that a bis(triazole) scaffold increased
      resistance to nucleophilic attack, with compound 27d being the most potent (Ki =
      10 MUM). In the process of reducing reactivity, we also prepared a new class of
      inhibitors, replacing the alkene of CP4d with an alkyne, leading to a significant
      increase in potency for compound 22b (Ki = 420 nM).

PMID- 30108748
TI  - Synthesis of substituted 2H-benzo[e]indazole-9-carboxylate as a potent
      antihyperglycemic agent that may act through IRS-1, Akt and GSK-3beta pathways.
AB  - Based on high throughput screening of our chemical library, we identified two 4,5
      dihydro-2H-benzo[e]indazole derivatives (5d and 5g), which displayed a
      significant effect on glucose uptake in L6 skeletal muscle cells. Based on these
      lead molecules, a series of benzo[e]indazole derivatives were prepared. Among all
      the synthesized dihydro-2H-benzo[e]indazoles, 8-(methylthio)-2-phenyl-6-p-tolyl
      4,5-dihydro-2H-benzo[e]indazole-9-carboxylate (5e) showed significant glucose
      uptake stimulation in L6 skeletal muscle cells, even better than lead compounds.
      Additionally, 5e decreased glucagon-induced glucose release in HepG2 hepatoma
      cells. The 2H-benzo[e]indazole 5e exerted an antihyperglycemic effect in normal,
      sucrose challenged streptozotocin-induced diabetic rats and type 2 diabetic db/db
      mice. Treatment with 5e at a dose of 30 mg kg-1 in db/db mice caused a
      significant decrease in triglyceride and total cholesterol levels and increased
      the HDL-C level in a significant manner. The mechanistic studies revealed that
      the 2H-benzo[e]indazole 5e significantly stimulated insulin-induced signaling at
      the level of IRS-1, Akt and GSK-3beta in L6 skeletal muscle cells, possibly by
      inhibiting protein tyrosine phosphatase-1B. This new 2H-benzo[e]indazole
      derivative has potential for the treatment of diabetes with improved lipid
      profile.

PMID- 30108750
TI  - Toxicity of tryptophan manganese(i) carbonyl (Trypto-CORM), against Neisseria
      gonorrhoeae.
AB  - The potential for carbon monoxide-releasing molecules (CO-RMs) as antimicrobials
      represents an exciting prospective in the fight against antibiotic resistance.
      Trypto-CORM, a tryptophan-containing manganese(i) carbonyl, is toxic against E.
      coli following photo-activation. Here, we demonstrate that Trypto-CORM is toxic
      against Neisseria gonorrhoeae in the absence of photoactivation. Trypto-CORM
      toxicity was reversed by the high CO affinity globin leg-haemoglobin (Leg-Hb),
      indicating that the toxicity is due to CO release. Release of CO from Trypto-CORM
      in the dark was also detected with Leg-Hb (but not myoglobin) in vitro. N.
      gonorrhoeae is more sensitive to CO-based toxicity than other model bacterial
      pathogens, and may serve as a viable candidate for antimicrobial therapy using CO
      RMs.

PMID- 30108751
TI  - Synthesis, characterization, solubilization, cytotoxicity and antioxidant
      activity of aminomethylated dihydroquercetin.
AB  - A dihydroquercetin derivative (DHQA) was prepared through aminomethylation to
      overcome the low water solubility and bioavailability of dihydroquercetin (DHQ).
      DHQA was characterized through HPLC, nuclear magnetic resonance, scanning
      electron microscopy, X-ray diffraction, and thermogravimetric analyses. DHQA was
      converted into the amorphous form, but the major structure of DHQ remained
      unchanged. Solubilization and dissolution tests were also performed. Results
      showed that the solubility and dissolution rates of DHQA were approximately 16.28
      and 6.31 times higher than those of DHQ, respectively. The MTT assay of DHQA
      showed a non-toxic effect against non-cancerous HEK-293T cells (EC50 = 820.00
      MUM), and potent inhibitory activity against cancerous Hela cells (EC50 = 138.17
      MUM). Finally, the antioxidant activity of DHQA was confirmed in vitro through
      DPPH and ABTS radical scavenging activity assays. DHQA displayed high antioxidant
      activities with low IC50 values (0.043 and 0.042 mM, respectively). Reducing Fe3+
      power assay indicated that DHQA exhibited higher reducing power than DHQ and
      ascorbic acid.

PMID- 30108746
TI  - ATM, ATR, CHK1, CHK2 and WEE1 inhibitors in cancer and cancer stem cells.
AB  - DNA inevitably undergoes a high number of damages throughout the cell cycle. To
      preserve the integrity of the genome, cells have developed a complex enzymatic
      machinery aimed at sensing and repairing DNA lesions, pausing the cell cycle to
      provide more time to repair, or induce apoptosis if damages are too severe. This
      so-called DNA-damage response (DDR) is yet considered as a major source of
      resistance to DNA-damaging treatments in oncology. Recently, it has been
      hypothesized that cancer stem cells (CSC), a sub-population of cancer cells
      particularly resistant and with tumour-initiating ability, allow tumour re-growth
      and cancer relapse. Therefore, DDR appears as a relevant target to sensitize
      cancer cells and cancer stem cells to classical radio- and chemotherapies as well
      as to overcome resistances. Moreover, the concept of synthetic lethality could be
      particularly efficiently exploited in DDR. Five kinases play pivotal roles in the
      DDR: ATM, ATR, CHK1, CHK2 and WEE1. Herein, we review the drugs targeting these
      proteins and the inhibitors used in the specific case of CSC. We also suggest
      molecules that may be of interest for preclinical and clinical researchers
      studying checkpoint inhibition to sensitize cancer and cancer stem cells to DNA
      damaging treatments.

PMID- 30108752
TI  - Evaluation of chemical modification effects on DNA plasmid transfection
      efficiency of single-walled carbon nanotube-succinate- polyethylenimine
      conjugates as non-viral gene carriers.
AB  - Polyethylenimine (PEI) is a widely used non-viral vector for DNA delivery. One
      major obstacle of higher molecular weight PEIs is the increased cytotoxicity
      despite the improved transfection efficiency and numerous chemical modifications
      that have been reported to overcome this problem. Carbon nanotubes (CNT) are
      carbon nanomaterials capable of penetrating into cell membranes with no cytotoxic
      effects. Covalent and noncovalent functionalization methods have been used to
      improve their solubility in aqueous media. The idea of conjugating PEIs and CNT
      through different chemical bonds and linkers seems promising as it may result in
      highly effective carriers due to combination of the transfection ability of PEI
      with cell internalization of CNT. In this study, six different water-soluble PEI
      conjugates of single-walled carbon nanotubes (SWNTs) were prepared by grafting
      PEI with one of three molecular weights (1.8, 10 and 25 kDa) through succinate as
      a linker which refers to "an organic moiety through which a SWNT is conjugated to
      PEI." The succinate linker was introduced to the surface of SWNTs through two
      different chemical strategies: a) ester and b) acyl linkages. The resulting SWNT
      PEI vectors were characterized by IR spectroscopy, thermogravimetric analysis
      (TGA) and SEM imaging. All synthesized carriers were evaluated and compared for
      their cytotoxicity and transfection efficiency in murine neuroblastoma cells as
      polyplexes with plasmid DNA for luciferase and green fluorescent protein (GFP).
      The most efficient carriers were prepared by attaching PEI with the lowest
      molecular weight (1.8 kDa) through acyl linkage, which gave a transfection
      efficiency 190-fold greater than that of the corresponding free PEI. Transfection
      efficiency was the highest in polyplexes prepared with acyl-linked conjugates in
      all the plasmid/vector ratios studied.

PMID- 30108753
TI  - Tracing compound pathways using chemical space networks.
AB  - Similarity-based compound networks are used as coordinate-free representations of
      chemical space. In so-called chemical space networks (CSNs), nodes represent
      compounds and edges pairwise similarity relationships. Nodes can be annotated
      with activity information, which enables visualization of structure-activity
      relationship (SAR) patterns. A major determinant of CSN structure and topology is
      the way in which similarity relationships are determined. Using different
      similarity measures, a number of CSN variants have been generated previously.
      Herein, we report a new type of CSN with an asymmetric similarity metric based
      upon the maximum common substructure of compound pairs. While CSNs have thus far
      mostly been used for SAR visualization, the new CSN variant was designed for
      another medicinal chemistry application, i.e. the identification of compound
      pathways in data sets. In this CSN, pathways consisting of structurally related
      compounds with increasing size can be systematically traced, which represent
      models of compound optimization paths. Compound series forming such paths can be
      extracted from the CSN. The network-based identification of hit-to-lead or lead
      optimization series in compound data sets is intuitive and thought to provide
      valuable information for medicinal chemistry.

PMID- 30108754
TI  - Synthesis and DNA/RNA complementation studies of peptide nucleic acids containing
      5-halouracils.
AB  - The monomers of peptide nucleic acids containing 5-halouracils (5-XU-PNA),
      incorporated into heptameric PNA in the middle position, have been synthesized.
      Thermodynamic analyses revealed that the heptameric PNA oligomer with DNA and RNA
      showed higher duplex stability compared to the unmodified PNA counterpart. NMR
      studies suggested that the electron withdrawing effect of the halogen atom
      increased the strength of the XU-A hydrogen bond.

PMID- 30108755
TI  - A histone H1-binding-aptide-based apoptosis imaging probe for monitoring tumor
      responses to cancer therapy.
AB  - Here we report the feasibility of using a high-affinity histone H1-binding
      peptide as a potential molecular apoptosis imaging probe. The Cy5.5-labeled
      peptide showed high selectivity for drug-treated apoptotic tumors compared with
      non-apoptotic tumors in various in vivo settings, enabling detection of tumor
      responses to both docetaxel chemotherapy and Herceptin antibody therapy as early
      as 12 hours after treatment with a high signal-to-background ratio, even at
      extremely low doses.

PMID- 30108756
TI  - Synthesis and biological evaluation of (-)-kunstleramide and its derivatives.
AB  - Stereoselective total synthesis of (-)-kunstleramide, a cytotoxic dienamide from
      the bark of Beilschmiedia kunstleri gamble, has been accomplished by using Keck's
      asymmetric allylation and Trost isomerization as key reactions. Application of
      the developed strategy for the synthesis of a series of amide analogues (8-22)
      was also reported. Furthermore, the synthesized compounds were evaluated for
      their in vitro anti-proliferative activities against human epithelial lung
      carcinoma (A549), human epithelial cervical cancer (HeLa), human breast
      adenocarcinoma (MCF7) and human neuroblastoma (IMR32) cell lines using the SRB
      assay. All the compounds show moderate anti-proliferative activity against all
      cell lines. Some of the piperazine derivatives (17-22) strongly inhibit the
      growth of breast cancer cells with IC50 values of 8-20 MUM.

PMID- 30108757
TI  - Light-responsive CO2 bubble-generating polymeric micelles for tumor cell
      ablation.
AB  - We report a novel UV-responsive polymeric micelle system based on coumarin ester
      for tumor treatment. The micelle itself can generate CO2 under UV exposure owing
      to the photolysis of (7-diethylaminocoumarin-4-yl)methyl (DEACM). Without loading
      any drugs, the micelle causes significant cell death under 8 s UV irradiation in
      vitro. This is the first time to use light to decompose the nano-carrier itself
      into CO2 bubbles for tumor cell ablation.

PMID- 30108758
TI  - Synthesis, antioxidant and antitumoral activities of 5'-arylchalcogeno-3
      aminothymidine (ACAT) derivatives.
AB  - This article presents the preparation and in vitro biological activities of new
      5'-arylchalcogeno-3-aminothymidine derivatives as antioxidants (inhibition of
      lipid peroxidation, scavenging of the free radical 2,2-diphenylpicrylhydrazyl and
      demonstration of a thiol peroxidase-like activity) as well as antitumoral agents
      against bladder carcinoma 5637. The chalcogeno-aminothymidines presented
      prominent activity in the tests for both biological properties, showing a direct
      relation with the chalcogenium atom.

PMID- 30108759
TI  - Encapsulation of a nitric oxide donor into a liposome to boost the enhanced
      permeation and retention (EPR) effect.
AB  - We propose a method to improve the enhanced permeability and retention (EPR)
      effect of nanomedicines based on tumor-specific vasodilation using a nitric oxide
      (NO) donor-containing liposome. NONOate, a typical NO donor, was incorporated
      into a PEGylated liposome to retard the protonation-induced release of NO from
      NONOate by the protecting lipid bilayer membrane. The NONOate-containing liposome
      (NONOate-LP) showed similar blood retention to an empty PEGylated liposome but
      almost twice the amount accumulated within the tumor. This improvement in the EPR
      effect is thought to have been caused by specific vasodilation in the tumor
      tissue by NO released from the NONOate-LP accumulated in the tumor. The improved
      EPR effect by NONOate-LP will be useful for the accumulation of co-administered
      nanomedicines.

PMID- 30108760
TI  - Diazabicyclo analogues of maraviroc: synthesis, modeling, NMR studies and
      antiviral activity.
AB  - Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is
      replaced by diazabicyclooctane or diazabicyclononane, were synthesized and
      tested, through a viral neutralization assay, on a panel of six pseudoviruses.
      The diazabicyclooctane derivative maintained a significant infectivity reduction
      power, whereas the diazabicyclononane was less effective. Biological data were
      rationalized through a computational study that allowed the conformational
      preferences of the compounds to be determined and a correlation between the
      inhibitory activity, the bridge length of the bicycle, and the rotational barrier
      around dihedral angle tau7 to be hypothesized. A high-field NMR analysis
      supported the modeling results.

PMID- 30108761
TI  - Aryl-alkyl-lysines: small molecular membrane-active antiplasmodial agents.
AB  - Due to emerging resistance there is a steady need for new antimalarial drugs.
      Here, we report a new class of water soluble, non-toxic compounds, aryl-alkyl
      lysines, with promising activity against the ring stage of Plasmodium falciparum.
      The optimal compound perturbed the plasma membrane potential and the digestive
      vacuole of parasites. In the murine model of malaria (Plasmodium berghei ANKA)
      the compound was able to increase the survival of mice by at least 5 days by an
      intra-peritoneal route. Further, the compounds showed no apparent toxicity to
      mice at the concentration tested.

PMID- 30108763
TI  - Pyrazolobenzothiazine-based carbothioamides as new structural leads for the
      inhibition of monoamine oxidases: design, synthesis, in vitro bioevaluation and
      molecular docking studies.
AB  - Two new series of pyrazolobenzothiazine-based carbothioamides (3a-o and 4a-o)
      were synthesized using saccharin as the starting material. The synthesized
      derivatives were investigated for their ability to inhibit monoamine oxidases
      (MAO). Compound 3b was found to be a very potent MAO-A inhibitor with an IC50
      value of 0.003 +/- 0.0007 MUM, while compound 4d was the most effective inhibitor
      of MAO-B having an IC50 value of 0.02 +/- 0.001 MUM. Molecular docking studies
      were performed to identify the probable binding modes in the active site of the
      monoamine oxidase enzymes. The synthetic and computational investigations in the
      current work suggested that these newly identified inhibitors may serve as a
      powerful starting point for the exploration and optimization of potential
      therapeutic agents targeting Parkinson's disease.

PMID- 30108762
TI  - Design, synthesis and cytotoxicity of bengamide analogues and their epimers.
AB  - Starting from d-glycero-d-gulo-heptonic acid gamma-lactone and amino acids, a
      number of diastereoisomeric bengamide analogues were synthesized. Optimization of
      the reaction conditions revealed that microwave irradiation assistance is a
      powerful method for the preparation of aminolactams, as well as for the coupling
      reactions of the lactone 5 with aminolactams. Cytotoxic activity evaluation
      against six cancer cell lines (KB, HepG2, LU1, MCF7, HL60, and Hela) demonstrated
      that the configuration of C-2' seems to be critical for the cytotoxic activity of
      compounds 8b (2'R) and 8a (2'S). Additionally, comparison of cytotoxicity of the
      protected acetonide compounds with that of their corresponding deprotected
      bengamide analogues suggested that the flexibility of the ketide side chain
      should be required for their cytotoxic activity.

PMID- 30108764
TI  - Synthesis and biological evaluation of 8-hydroxy-2,7-naphthyridin-2-ium salts as
      novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE).
AB  - By analogy with the natural product chelerythrine, which has been identified as
      an inhibitor of both acetylcholinesterase (AChE) and butyrylcholinesterase
      (BChE), we prepared a small series of 8-hydroxy-2,7-naphthyridin-2-ium salts.
      Spectroscopic analyses allowed us to elucidate the zwitterionic nature of 2,7
      naphthyridin-1(7H)-ones, the neutral state of 8-hydroxy-2,7-naphthyridin-2-ium
      salts. Among the tested compounds, we identified dual inhibitors of AChE and BChE
      as well as an inhibitor showing a preferential inhibition of AChE over BChE. By
      in vitro characterization in combination with docking studies, we were able to
      identify structural features that influence the biological activity of 8-hydroxy
      2,7-naphthyridin-2-ium salts.

PMID- 30108765
TI  - Synthesis and evaluation of small molecules bearing a benzyloxy substituent as
      novel and potent monoamine oxidase inhibitors.
AB  - A new series of small molecules bearing a benzyloxy substituent have been
      designed, synthesized and evaluated for hMAO inhibitory activity in vitro. Most
      of the compounds were potent and selective MAO-B inhibitors, and were weak
      inhibitors of MAO-A. In particular, compounds 9e (IC50 = 0.35 MUM) and 10e (IC50
      = 0.19 MUM) were the most potent MAO-B inhibitors, and exhibited the highest
      selectivity for MAO-B (9e, SI > 285.7-fold and 10e, SI = 146.8-fold). In
      addition, the structure-activity relationships for MAO-B inhibition indicated
      that electron-withdrawing groups in the open small molecules were more suitable
      for MAO-B inhibition, and substitutions at the benzyloxy of the open small
      molecules, particularly with the halogen substituted benzyloxy, were more
      favorable for MAO-B inhibition. Molecular docking studies have been done to
      explain the potent MAO-B inhibition of the open small molecules. Furthermore, the
      representative compounds 9e and 10e showed low neurotoxicity in SH-SY5Y cells in
      vitro. So the small molecules bearing the benzyloxy substituent could be used to
      develop promising drug candidates for the therapy of neurodegenerative diseases.

PMID- 30108766
TI  - Outstanding Reviewers for MedChemComm in 2016.
AB  - We would like to take this opportunity to highlight the Outstanding Reviewers for
      MedChemComm in 2016, as selected by the editorial team for their significant
      contribution to the journal.

PMID- 30108767
TI  - Structure-activity relationships for the synthesis of selective cyclooxygenase 2
      inhibitors: an overview (2009-2016).
AB  - Most drugs used to treat pain and inflammation act through inhibition of the
      enzymes prostaglandin G/H synthase, commonly known as cyclooxygenase (COX). Among
      these, the simultaneous inhibition of cyclooxygenase 1 (COX-1) would explain the
      unwanted side effects in the gastrointestinal tract and many adverse
      cardiovascular effects, such as high blood pressure, myocardial infarction and
      thrombosis. These side effects led in time to the development of NSAIDs that
      behave as selective COX-2 inhibitors. This manuscript highlights the structure
      activity relationships which characterize the chemical scaffolds endowed with
      selective COX-2 inhibition. Additionally, the role of COX-2 inhibitors in the
      pain phenomenon and cancer is discussed.

PMID- 30108768
TI  - Recent advances in the medicinal chemistry of group II and group III mGlu
      receptors.
AB  - Metabotropic glutamate receptors (mGlu receptors) belong to the G-protein-coupled
      receptors superfamily. They are divided into three groups, in which group II and
      group III belong to presynaptic receptors that negatively modulate glutamate and
      gamma-aminobutyric acid (GABA) release when activated. In this review, we
      introduce not only the functions of mGlu receptors, but also the group II and
      group III allosteric modulators and agonists/antagonists reported over the past
      five years according to a classification of their structures, with a specific
      focus on their biological activity and selectivity. In particular, the structure
      of these compounds and the future directions of ideal candidates are highlighted.

PMID- 30108773
TI  - Designing safer oral drugs.
AB  - Designing an oral drug such that its estimated dose to humans is both efficacious
      and safe is challenging. During the early design stage, where in vitro or
      preclinical species in vivo safety data are limited, heuristic-based criteria
      often related to physicochemical properties are used for guidance. The causal
      relationship between a compound's log P and its human in vivo toxicity is
      considered. With respect to designing efficacious oral drugs that potentially
      have reduced toxicity liabilities, an alternative heuristic-based criterion is
      proposed based on the amount of compound in the body at steady state. In humans,
      a threshold for the amount of compound in the body at steady state of 0.5 mg kg-1
      is suggested. The criterion is based on the minimum toxic blood-plasma
      concentration that produces clinically relevant side effects or symptoms in
      humans for 242 oral drugs. It can be used to estimate a therapeutic window
      against which a compound's estimated in vivo plasma levels for a particular dose
      size and frequency can be assessed. The relationship between this criterion and
      acceptable oral dose sizes for different charge types with different in vivo
      plasma clearances is discussed.

PMID- 30108771
TI  - N-tert-Prenylation of the indole ring improves the cytotoxicity of a short
      antagonist G analogue against small cell lung cancer.
AB  - Natural prenylated indoles have been proposed as potential anticancer agents. To
      exploit this discovery for developing new peptide therapeutics, we report the
      first studies whereby incorporation of prenylated indoles into primary sequences
      has been achieved. We developed a route to synthesise Nalpha-Fmoc-protected
      tryptophan derivatives in which the prenyl group is linked to the N-indole core,
      using Pd(ii)-mediated C-H functionalisation of 2-methyl-2-butene. Based on the
      Substance P antagonist G (SPG), a well-known Small Cell Lung Cancer (SCLC)
      anticancer agent, we designed a new penta-peptide sequence to include a prenyl
      moiety on one of the tryptophan residues. The N-tert-prenylated tryptophan
      analogue was assembled into the pentameric peptide using standard solid phase
      peptide synthesis or liquid phase synthesis by fragment coupling. In vitro
      screening showed that the N-tert-prenylation of the indole ring on the tryptophan
      residue located near the C-terminal of the penta-peptide enhanced the
      cytotoxicity against H69 (IC50 = 2.84 +/- 0.14 MUM) and DMS79 (IC50 = 4.37 +/-
      0.44 MUM) SCLC cell lines when compared with the unmodified penta-peptide (H69,
      IC50 = 30.74 +/- 0.30 MUM and DMS79, IC50 = 23.00 +/- 2.07 MUM) or the parent SPG
      sequence (IC50 > 30 MUM, both cell lines). SCLC almost invariably relapses with
      therapy-resistant disease. The DMS79 cell line was established from a patient
      following treatment with a number of chemotherapeutics (cytoxan, vincristine and
      methotrexate) and radiation therapy. Treating DMS79 tumour-bearing nude mice
      provided a human xenograft model of drug resistance to test the efficacy of the
      prenylated peptide. A low dose (1.5 mg kg-1) of the prenylated peptide was found
      to reduce tumour growth by ~30% (P < 0.05) at day 7, relative to the control
      group receiving vehicle only. We conclude that the availability of the Fmoc-Trp(N
      tert-prenyl)-OH amino acid facilitates the synthesis of prenylated-tryptophan
      containing peptides to explore their therapeutic potential.

PMID- 30108769
TI  - A review on cell wall synthesis inhibitors with an emphasis on glycopeptide
      antibiotics.
AB  - Cell wall biosynthesis inhibitors (CBIs) have historically been one of the most
      effective classes of antibiotics. They are the most extensively used class of
      antibiotics and their importance is exemplified by the beta-lactams and
      glycopeptide antibiotics. However, this class of antibiotics has not received
      impunity from resistance development. In the wake of this predicament, this
      review presents the progress of CBIs, especially glycopeptide derivatives as
      antibiotics to confront antibacterial resistance. The various strategies used for
      the development of CBIs, their clinical status and possible directions in which
      this field can evolve have also been discussed.

PMID- 30108772
TI  - Design, synthesis, molecular-docking and antimycobacterial evaluation of some
      novel 1,2,3-triazolyl xanthenones.
AB  - As part of an ongoing effort to develop new antitubercular and antimicrobial
      agents, a series of substituted xanthenone derivatives (7a-p) were synthesized.
      Xanthenone derivatives (7a-p) were prepared via a one-pot three-component thermal
      cyclization reaction of beta-naphthol (5), substituted 1-aryl-1H-[1,2,3]triazole
      4-carbaldehydes (4a-h), and cyclic-1,3-diones (6a, b) in the presence of a
      catalytic amount of iodine. The newly synthesized compounds were characterized by
      IR, NMR, mass spectral data, and elemental analysis. These compounds (4a-h and 7a
      p) were screened for in vitro antitubercular activity against the M. tuberculosis
      H37Rv (ATCC 27294) strain, for antibacterial activity against Gram-positive and
      Gram-negative strains, and for antifungal activity against a pathogenic strain of
      fungi. Among the compounds tested, most of them showed good to excellent
      antimicrobial and antitubercular activity. The active compounds displaying good
      potency in the MTB were further examined for toxicity in a HEK cell line. In
      addition, the structure and antitubercular activity relationship were further
      supported by in silico molecular-docking studies of the active compounds against
      the pantothenate synthetase (PS) enzyme of M. tuberculosis.

PMID- 30108775
TI  - Discovery of potent human lactate dehydrogenase A (LDHA) inhibitors with
      antiproliferative activity against lung cancer cells: virtual screening and
      biological evaluation.
AB  - Human lactate dehydrogenase A (LDHA) plays a crucial role in the promotion of
      glycolysis in invasive tumor cells, and recently, it has been considered as a
      vital therapeutic target in the field of oncology. Herein, by combining docking
      based virtual screening with in vitro biochemical evaluation, we report the
      discovery of a potent LDHA inhibitor with antiproliferative activity. The
      enzymatic assay suggested that the identified compound 7 has a good inhibitory
      activity (IC50 = 0.36 MUM) against LDHA. The in vitro cytotoxicity assay
      demonstrated that compound 7 reduces the growth of A549 and NCI-H1975 lung cancer
      cells, with EC50 values of 5.5 and 3.0 MUM, respectively. These findings indicate
      that compound 7 could be employed as a useful probe to explore the pharmacology
      of LDHA.

PMID- 30108770
TI  - Protein-ligand (un)binding kinetics as a new paradigm for drug discovery at the
      crossroad between experiments and modelling.
AB  - In the last three decades, protein and nucleic acid structure determination and
      comprehension of the mechanisms, leading to their physiological and pathological
      functions, have become a cornerstone of biomedical sciences. A deep understanding
      of the principles governing the fates of cells and tissue at the molecular level
      has been gained over the years, offering a solid basis for the rational design of
      drugs aimed at the pharmacological treatment of numerous diseases. Historically,
      affinity indicators (i.e. Kd and IC50/EC50) have been assumed to be valid
      indicators of the in vivo efficacy of a drug. However, recent studies pointed out
      that the kinetics of the drug-receptor binding process could be as important or
      even more important than affinity in determining the drug efficacy. This
      eventually led to a growing interest in the characterisation and prediction of
      the rate constants of protein-ligand association and dissociation. For instance,
      a drug with a longer residence time can kinetically select a given receptor over
      another, even if the affinity for both receptors is comparable, thus increasing
      its therapeutic index. Therefore, understanding the molecular features underlying
      binding and unbinding processes is of central interest towards the rational
      control of drug binding kinetics. In this review, we report the theoretical
      framework behind protein-ligand association and highlight the latest advances in
      the experimental and computational approaches exploited to investigate the
      binding kinetics.

PMID- 30108774
TI  - The molecular basis of the interactions between synthetic retinoic acid analogues
      and the retinoic acid receptors.
AB  - All-trans-retinoic acid (ATRA) and its synthetic analogues EC23 and EC19 direct
      cellular differentiation by interacting as ligands for the retinoic acid receptor
      (RARalpha, beta and gamma) family of nuclear receptor proteins. To date, a number
      of crystal structures of natural and synthetic ligands complexed to their target
      proteins have been solved, providing molecular level snap-shots of ligand
      binding. However, a deeper understanding of receptor and ligand flexibility and
      conformational freedom is required to develop stable and effective ATRA analogues
      for clinical use. Therefore, we have used molecular modelling techniques to
      define RAR interactions with ATRA and two synthetic analogues, EC19 and EC23, and
      compared their predicted biochemical activities to experimental measurements of
      relative ligand affinity and recruitment of coactivator proteins. A comprehensive
      molecular docking approach that explored the conformational space of the ligands
      indicated that ATRA is able to bind the three RAR proteins in a number of
      conformations with one extended structure being favoured. In contrast the
      biologically-distinct isomer, 9-cis-retinoic acid (; 9CRA), showed significantly
      less conformational flexibility in the RAR binding pockets. These findings were
      used to inform docking studies of the synthetic retinoids EC23 and EC19, and
      their respective methyl esters. EC23 was found to be an excellent mimic for ATRA,
      and occupied similar binding modes to ATRA in all three target RAR proteins. In
      comparison, EC19 exhibited an alternative binding mode which reduces the strength
      of key polar interactions in RARalpha/gamma but is well-suited to the larger
      RARbeta binding pocket. In contrast, docking of the corresponding esters revealed
      the loss of key polar interactions which may explain the much reduced biological
      activity. Our computational results were complemented using an in vitro binding
      assay based on FRET measurements, which showed that EC23 was a strongly binding,
      pan-agonist of the RARs, while EC19 exhibited specificity for RARbeta, as
      predicted by the docking studies. These findings can account for the distinct
      behaviour of EC23 and EC19 in cellular differentiation assays, and additionally,
      the methods described herein can be further applied to the understanding of the
      molecular basis for the selectivity of different retinoids to RARalpha, beta and
      gamma.

PMID- 30108776
TI  - Comparison of free-radical inhibiting antioxidant properties of carvedilol and
      its phenolic metabolites.
AB  - Carvedilol is a widely prescribed drug for the treatment of heart failure and the
      prevention of associated ventricular arrhythmias. It has also been reported to
      function as a biological antioxidant via hydrogen atom transfer from its
      carbazole N-H moiety to chain-propagating radicals. Metabolites of the drug
      include phenolic derivatives, such as 3-hydroxy-, 4'-hydroxy- and 5'
      hydroxycarvedilol, which are also potential antioxidants. A comparison of the
      radical-inhibiting activities of the parent drug and the three metabolites was
      carried out in two separate assays. In the first, hydrogen atom transfer from
      these four compounds to the stable radical DPPH was measured by the decrease in
      the UV-visible absorption at 515 nm of the latter. The known radical inhibitors
      BHT, 4-hydroxycarbazole and alpha-tocopherol were employed as benchmarks in
      parallel experiments. In the second assay, inhibition of the photoinduced free
      radical 1,2-addition of Se-phenyl p-tolueneselenosulfonate to
      cyclopropylacetylene, along with competing ring-opening of the cyclopropane ring,
      was monitored by 1H NMR spectroscopy in the presence of the carvedilol-based and
      benchmark antioxidants. In both assays, carvedilol displayed negligible
      antioxidant activity, while the three metabolites all proved superior radical
      inhibitors to BHT, with radical-quenching abilities in the order 3-hydroxy- > 5'
      hydroxy > 4'-hydroxycarvedilol. Among the metabolites, 3-hydroxycarvedilol
      displayed even stronger activity in both assays than alpha-tocopherol, the best
      of the benchmark antioxidants. These results suggest that the radical-inhibiting
      antioxidant properties that have been attributed to carvedilol are largely or
      exclusively due to its metabolites and not to the parent drug itself.

PMID- 30108778
TI  - Identification of mitoxantrone as a new inhibitor of ROS1 fusion protein in non
      small cell lung cancer cells.
AB  - Mitoxantrone, an FDA-approved drug for multiple sclerosis and hormone refractory
      prostate cancer, is identified as a potent inhibitor of ROS1 fusion protein by in
      silico screening in non-small cell lung cancer cells. Mitoxantrone can suppress
      the phosphorylation of ROS1 and subsequently inhibit its downstream signaling
      pathway and thus induce cell apoptosis.

PMID- 30108777
TI  - (Indolylalkyl)piperidine carbamates as inhibitors of fatty acid amide hydrolase
      (FAAH).
AB  - A series of phenyl 4-[(indol-1-yl)alkyl]piperidine carbamates was synthesized and
      tested for inhibition of the endocannabinoid degrading enzyme fatty acid amide
      hydrolase (FAAH) and for metabolic stability in rat liver S9 fractions and
      porcine blood plasma. Structure-activity relationship studies revealed that
      variation of the length of the alkyl spacer connecting the indole and the
      piperidine heterocycle, introduction of substituents into the indole ring,
      replacement of the piperidine by a piperazine scaffold as well as opening of the
      piperidine ring system affect activity significantly. The metabolic stability of
      this compound class proved to be significantly higher than that of corresponding
      phenyl N-(indol-1-ylalkyl)carbamates.

PMID- 30108779
TI  - Neuroprotective effect of single-wall carbon nanotubes with built-in peroxidase
      like activity against beta-amyloid-induced neurotoxicity.
AB  - Carbon nanotubes (CNTs) have emerged as a leading nanomaterial for biomedical
      applications because of their extraordinary properties, which make them useful as
      delivery vehicles for drugs, proteins, and DNA into cells. However, the numerous
      applications of carbon nanotubes inevitably increase the potential risk of this
      nanomaterial. To address this issue, it is necessary to develop protocols for the
      effective and safe degradation of CNTs. In this study, we demonstrate a self
      degradation route for single-wall carbon nanotubes mediated by the built-in
      peroxidase-like activity of bacterial magnetic nanoparticles (BMPs).
      Biocompatible BMPs which originated from Magnetospirillum sp. AMB-1 were directly
      conjugated through covalent bonding to functionalized SWNTs (f-SWNTs) without any
      additional functionalization processes. This SWNT-BMP hybrid was proven to
      exhibit highly synergetic peroxidase-like activity, and BMPs act as a highly
      effective intrinsic peroxidase for the self-degradation of BMP-decorated SWNTs.
      Moreover, it was shown to be an inhibitor that reduces the formation of beta
      amyloid (Abeta) fibrils, which are considered a key element in Alzheimer's
      disease. Thereby the SWNT-BMP hybrid exerts neuroprotective effects against beta
      amyloid (Abeta) fibrillation-induced neurotoxicity in SH-SY5Y human neuroblastoma
      cells. These results suggest that the SWNT-BMP hybrid could offer a new approach
      for treating or preventing neurodegenerative diseases.

PMID- 30108780
TI  - Synthesis and antitumor mechanism of a new iron(iii) complex with 5,7-dichloro-2
      methyl-8-quinolinol as ligands.
AB  - A new iron(iii) complex with 5,7-dichloro-2-methyl-8-quinolinol (HClMQ) as
      ligands, i.e., [Fe(ClMQ)2Cl] (1), was synthesized and evaluated for its
      anticancer activity. Compared to the HClMQ ligand, complex 1 showed a higher
      cytotoxicity towards a series of tumor cell lines, including Hep-G2, BEL-7404,
      NCI-H460, A549, and T-24, with IC50 values in the range of 5.04-14.35 MUM.
      Notably, the Hep-G2 cell line was the most sensitive to complex 1. Mechanistic
      studies indicated that complex 1 is a telomerase inhibitor targeting c-myc G
      quadruplex DNA and can trigger cell apoptosis via inducing cell cycle arrest and
      DNA damage.

PMID- 30108781
TI  - Multivalent ligands for the serotonin 5-HT4 receptor.
AB  - 5-HT4 receptors are known to form constitutive dimers in membranes. To explore
      whether multivalency can enhance ligand interactions and/or efficacy in 5-HT4
      receptors, the structure of the partial agonist ML10302 was modified with
      oligo(ethylene glycol) chains, thus generating, by a gradual approach, short and
      long tethered bivalent or tetravalent ligands and the corresponding spanner
      linked monovalent controls. Both bivalent and tetravalent ligands displayed a 10
      20-fold increase in binding affinity compared to appropriate controls, but no
      multivalent ligand showed greater binding energy than ML10302 itself.
      Furthermore, the direct assessment of receptor-Gs interaction and studies of cAMP
      signalling indicated that multivalency does not enhance the efficacy of ML10302.

PMID- 30108782
TI  - Design, synthesis and evaluation of new ligustrazine derivatives as potential
      plasma-stable neuroprotective agents.
AB  - A series of ligustrazine-phenolic acid esters which exhibited promising
      neuroprotective activities have previously been reported. Nevertheless, we found
      that these ester compounds (like T-VA) were not stable in plasma by further in
      vivo studies. To investigate plasma-stable neuroprotective agents, a series of
      new ligustrazine derivatives were synthesized by conjoining ligustrazine and
      phenols with ester, ether and amide bonds. Most of the compounds exhibited higher
      protective effects against CoCl2-induced neurotoxicity in differentiated PC12
      cells than ligustrazine. Structure-activity relationships were also briefly
      discussed. We found that compound 2c (2-((2-methoxy-4-(((3,5,6-trimethylpyrazin-2
      yl)methoxy) methyl)phenoxy)methyl)-3,5,6-trimethylpyrazine) displayed the highest
      protective effect on the PC12 cells damaged by CoCl2 (EC50 = 1.07 MUM).
      Preliminary stability investigation in rat plasma was verified in vitro and
      better plasma stability was observed with 2c in comparison to T-VA.

PMID- 30108783
TI  - Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a
      novel, highly potent and specific inhibitor of mitochondrial complex I.
AB  - By probing the quinone substrate binding site of mitochondrial complex I with a
      focused set of quinazoline-based compounds, we identified substitution patterns
      as being critical for the observed inhibition. The structure activity
      relationship study also resulted in the discovery of the quinazoline 4-N-[2-(4
      phenoxyphenyl)ethyl]quinazoline-4,6-diamine (EVP4593) as a highly potent
      inhibitor of the multisubunit membrane protein. EVP4593 specifically and
      effectively reduces the mitochondrial complex I-dependent respiration with no
      effect on the respiratory chain complexes II-IV. Similar to established Q-site
      inhibitors, EVP4593 elicits the release of reactive oxygen species at the flavin
      site of mitochondrial complex I. Recently, EVP4593 was nominated as a lead
      compound for the treatment of Huntingtons disease. Our results challenge the
      postulated primary mode-of-action of EVP4593 as an inhibitor of NF-kappaB pathway
      activation and/or store-operated calcium influx.

PMID- 30108784
TI  - Design, synthesis and cytotoxic activity of water-soluble quinones with dibromo-p
      benzoquinone cores and amino oligo(ethylene glycol) side chains against MCF-7
      breast cancer cells.
AB  - A series of novel quinones was synthesized by reacting tetrabromo-p-benzoquinone
      with amino oligo(ethylene glycol) dendrons of generation numbers g = 0-2.
      According to the performed shake-flask experiments, their aqueous solubility (S =
      18 mg l-1-1.6 g ml-1) and partition coefficients (log Poct/wat = 2.53-0.21) can
      be tuned in a wide range as a function of g. In vitro cytotoxicity assays of
      tetrabromo-p-benzoquinone and its derivatives against MCF-7 human breast cancer
      cells showed a concentration- and generation-specific biological activity with
      IC50-values as low as 0.8 MUM. Further investigations revealed a considerable
      selectivity against cancer cells, as indicated by a weak cytotoxicity against
      human skin fibroblast cells (>80% survival) within the studied range of
      concentrations. The results demonstrate that these novel amino oligo(ethylene
      glycol) dendrons depict versatile tools to ameliorate physical and
      pharmacological characteristics of extremely hydrophobic molecules and make them
      susceptible to biological applications.

PMID- 30108785
TI  - 68Ga-Chelation and comparative evaluation of N,N'-bis-[2-hydroxy-5
      (carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC) conjugated NGR
      and RGD peptides as tumor targeted molecular imaging probes.
AB  - Peptides containing RGD and NGR motifs display high affinity towards tumor
      vasculature molecular markers, integrin alphavbeta3 and CD13 receptors,
      respectively. In the present study, RGD and NGR peptides were conjugated with the
      novel acyclic chelator N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine
      N,N'-diacetic acid (HBED-CC) for radiolabeling with 68Ga. The radiotracers [68Ga
      HBED-CC-c(NGR)] and [68Ga-HBED-CC-c(RGD)] were quite hydrophilic with respective
      log P values being -2.8 +/- 0.14 and -2.1 +/- 0.17. 68Ga-HBED-CC-c(RGD) displayed
      a significantly higher (p < 0.05) uptake in murine melanoma B16F10 tumors as
      compared to 68Ga-HBED-CC-c(NGR) indicating its higher specificity towards
      integrin alphavbeta3-positive tumors. The two radiotracers showed similar uptake
      in CD13-positive human fibrosarcoma HT-1080 tumor xenografts (~1.5 +/- 0.2% ID g
      1). The tumor uptake of the two radiotracers was significantly reduced (p < 0.05)
      in both animal models during blocking studies. The tumor-to-blood ratio was
      observed to be ~2-2.5 for the two radiotracers, whereas the tumor-to-muscle ratio
      was significantly higher (p < 0.005) for 68Ga-HBED-CC-c(RGD) in the two animal
      models. The two radiotracers 68Ga-HBED-CC-c(NGR) and 68Ga-HBED-CC-c(RGD)
      exhibited renal excretion with rapid clearance from blood and other non-target
      organs. Thus, 68Ga-chelated HBED-CC conjugated NGR and RGD peptides expressed
      features conducive towards development as tumor targeted molecular imaging
      probes. This study further opens avenues for the successful conjugation of
      different peptides with the acyclic chelator HBED-CC and expansion of 68Ga-based
      radiopharmaceuticals.

PMID- 30108787
TI  - Contributors to 'New Talent: Americas'.
AB  - MedChemComm profiles the contributors to the 'New Talent: Americas' themed issue.

PMID- 30108786
TI  - Cholecystokinin-2/gastrin antagonists: 5-hydroxy-5-aryl-pyrrol-2-ones as anti
      inflammatory analgesics for the treatment of inflammatory bowel disease.
AB  - Arylated 5-hydroxy-pyrrol-2-ones were prepared in 2 synthetic steps from
      mucochloric acid and optimised as CCK2-selective ligands using radiolabelled
      binding assays. CCK antagonism was confirmed for the ligands in isolated tissue
      preparations. DSS (dextran sulfate sodium)-induced inflammation was analysed for
      derivative 7 and PNB-001 with L-365,260 as a standard. The IC50 of PNB-001 was
      determined to be 10 nM. Subsequent in vivo evaluation confirmed anti-inflammatory
      activity with respect to IBD assays. The best molecule, PNB-001, showed analgesic
      activity in the formalin test and in the hotplate assay, in which the analgesic
      effect of 1.5 mg kg-1 PNB-001 was equivalent to 40 mg kg-1 tramadol. The CCK2
      selective antagonist PNB-001 protected rats against indomethacin-induced
      ulceration at similar doses. The GI protection activity was found to be more
      potent than that of the 10 mg kg-1 dose of prednisolone, which served as a
      standard.

PMID- 30108788
TI  - Identification of imidazo[1,2-b]pyridazine TYK2 pseudokinase ligands as potent
      and selective allosteric inhibitors of TYK2 signalling.
AB  - As a member of the Janus (JAK) family of non-receptor tyrosine kinases, TYK2
      mediates the signaling of pro-inflammatory cytokines including IL-12, IL-23 and
      type 1 interferon (IFN), and therefore represents an attractive potential target
      for treating the various immuno-inflammatory diseases in which these cytokines
      have been shown to play a role. Following up on our previous report that ligands
      to the pseudokinase domain (JH2) of TYK2 suppress cytokine-mediated receptor
      activation of the catalytic (JH1) domain, the imidazo[1,2-b]pyridazine (IZP) 7
      was identified as a promising hit compound. Through iterative modification of
      each of the substituents of the IZP scaffold, the cellular potency was improved
      while maintaining selectivity over the JH1 domain. These studies led to the
      discovery of the JH2-selective TYK2 inhibitor 29, which provided encouraging
      systemic exposures after oral dosing in mice. Phosphodiesterase 4 (PDE4) was
      identified as an off-target and potential liability of the IZP ligands, and
      selectivity for TYK2 JH2 over this enzyme was obtained by elaborating along
      selectivity vectors determined from analyses of X-ray co-crystal structures of
      representative ligands of the IZP class bound to both proteins.

PMID- 30108789
TI  - Chitosan nanoparticles for nitric oxide delivery in human skin.
AB  - The use of nanoparticle-based transdermal delivery systems is a promising
      approach to efficiently carry and deliver therapeutic agents for dermal and
      systemic administration. Nitric oxide (NO) is a key molecule that plays important
      roles in human skin such as the control of skin homeostasis, skin defense,
      control of dermal blood flow, and wound healing. In addition, human skin contains
      stores of NO derivatives that can be mobilized and release free NO upon UV
      irradiation with beneficial cardiovascular effects, for instance the control of
      blood pressure. In this work, the NO donor precursor glutathione (GSH) was
      encapsulated (encapsulation efficiency of 99.60%) into ultra-small chitosan
      nanoparticles (CS NPs) (hydrodynamic size of 30.65 +/- 11.90 nm). GSH-CS NPs have
      a core-shell structure, as revealed by atomic force microscopy and X-ray
      photoelectron spectroscopy, in which GSH is protected in the nanoparticle core.
      Nitrosation of GSH by nitrous acid led to the formation of the NO donor S
      nitrosogluthathione (GSNO) into CS NPs. The GSNO release from the CS NPs followed
      a Fickian diffusion described by the Higuchi mathematical model. Topical
      application of GSNO-CS NPs in intact human skin significantly increased the
      levels of NO and its derivatives in the epidermis, as assayed by confocal
      microscopy, and this effect was further enhanced by skin irradiation with UV
      light. Therefore, NO-releasing CS NPs are suitable materials for transdermal NO
      delivery to local and/or systemic therapies.

PMID- 30108790
TI  - Microwave-enhanced Friedlander synthesis for the rapid assembly of halogenated
      quinolines with antibacterial and biofilm eradication activities against drug
      resistant and tolerant bacteria.
AB  - Herein, we disclose the development of a catalyst- and protecting-group-free
      microwave-enhanced Friedlander synthesis which permits the single-step,
      convergent assembly of diverse 8-hydroxyquinolines with greatly improved reaction
      yields over traditional oil bath heating (increased from 34% to 72%). This rapid
      synthesis permitted the discovery of novel biofilm-eradicating halogenated
      quinolines (MBECs = 1.0-23.5 MUM) active against MRSA, MRSE, and VRE. These small
      molecules exhibit activity through mechanisms independent of membrane lysis,
      further demonstrating their potential as a clinically useful treatment option
      against persistent biofilm-associated infections.

PMID- 30108792
TI  - Discovery of cyclopropyl chromane-derived pyridopyrazine-1,6-dione gamma
      secretase modulators with robust central efficacy.
AB  - Herein we describe the discovery of a novel series of cyclopropyl chromane
      derived pyridopyrazine-1,6-dione gamma-secretase modulators for the treatment of
      Alzheimer's disease (AD). Using ligand-based design tactics such as
      conformational analysis and molecular modeling, a cyclopropyl chromane unit was
      identified as a suitable heterocyclic replacement for a naphthyl moiety that was
      present in the preliminary lead 4. The optimized lead molecule 44 achieved good
      central exposure resulting in robust and sustained reduction of brain amyloid
      beta42 (Abeta42) when dosed orally at 10 mg kg-1 in a rat time-course study.
      Application of the unpaced isolated heart Langendorff model enabled efficient
      differentiation of compounds with respect to cardiovascular safety, highlighting
      how minor structural changes can greatly impact the safety profile within a
      series of compounds.

PMID- 30108791
TI  - Identification of potent tricyclic prodrug S1P1 receptor modulators.
AB  - Recently, our research group reported the identification of prodrug amino-alcohol
      2 as a potent and efficacious S1P1 receptor modulator. This molecule is
      differentiated preclinically over the marketed drug fingolimod (Gilenya 1), whose
      active phosphate metabolite is an S1P1 full agonist, in terms of pulmonary and
      cardiovascular safety. S1P1 partial agonist 2, however, has a long half-life in
      rodents and was projected to have a long half-life in humans. The purpose of this
      communication is to disclose highly potent partial agonists of S1P1 with shorter
      half-lives relative to the clinical compound 2. PK/PD relationships as well as
      their preclinical pulmonary and cardiovascular safety assessment are discussed.

PMID- 30108793
TI  - Discovery and hit-to-lead evaluation of piperazine amides as selective, state
      dependent NaV1.7 inhibitors.
AB  - NaV1.7 is a particularly compelling target for the treatment of pain. Herein, we
      report the discovery and evaluation of a series of piperazine amides that exhibit
      state-dependent inhibition of NaV1.7. After demonstrating significant
      pharmacodynamic activity with early lead compound 14 in a NaV1.7-dependent
      behavioural mouse model, we systematically established SAR trends throughout each
      sector of the scaffold. The information gleaned from this modular analysis was
      then applied additively to quickly access analogues that encompass an optimal
      balance of properties, including NaV1.7 potency, selectivity over NaV1.5, aqueous
      solubility, and microsomal stability.

PMID- 30108794
TI  - Design and synthesis of cenocladamide analogues and their evaluation against
      breast cancer cell lines.
AB  - This work describes the total synthesis of the alkaloid cenocladamide and a
      concise library of nine structural analogues aiming at their evaluation against
      the breast cancer cell line MDA-MB-231. The most promising compound (3; IC50 =
      6.6 MUM) was also evaluated in a panel of seven breast cancer cell lines and two
      non-tumorigenic cell lines. We further conducted an initial investigation on the
      mechanism of action of analogue 3, which lacks the endocyclic double bond when
      compared to cenocladamide. The present study presents the discovery of a
      cenocladamide analogue with interesting cytotoxic activity, which could be useful
      for further optimization towards new chemotherapeutic agents for breast cancer
      treatment.

PMID- 30108795
TI  - Quantitative measurement of intracellular HDAC1/2 drug occupancy using a trans
      cyclooctene largazole thiol probe.
AB  - Histone deacetylases (HDACs) regulate diverse cellular processes, and are
      promising targets for a number of diseases. Here we describe the design and
      utilization of a largazole-based chemical probe to quantitatively measure the
      intracellular occupancy of HDAC1 and HDAC2 by dacinostat. Surprisingly, the probe
      was unable to enrich HDAC3 despite its nanomolar potency in a biochemical assay,
      further proving the necessity of cell-based target occupancy assays to understand
      compound potency in physiologically-relevant settings. This occupancy assay has
      the potential to aid the development of novel HDAC1/2 inhibitors in drug
      discovery.

PMID- 30108797
TI  - Development of inverse electron demand Diels-Alder ligation and TR-FRET assays
      for the determination of ligand-protein target occupancy in live cells.
AB  - Determination of target engagement following drug administration under
      physiological conditions is essential for understanding clinical outcomes of
      therapeutic candidates. While the list of potential techniques that enable
      studies of target engagement is continuously expanding, identification of the
      best method to evaluate interactions between a ligand and its cellular binding
      partner(s) remains far from straightforward. We developed and compared the
      applicability of two label-based techniques; inverse electron demand Diels-Alder
      (IED-DA) ligation-based pull-down and TR-FRET assays for in-cell determination of
      target occupancy of c-Src kinase and p38-alpha kinase by the reversible inhibitor
      Dasatinib. Significantly, none of the assays required engineering proteins-of
      interest. Moreover, cellular TR-FRET assay emerged as a very promising platform
      for the determination of target occupancy of specific protein in a high
      throughput manner. Our studies suggest that both IED-DA assay and TR-FRET assay
      should be considered as methods of choice for the determination of target
      engagement of small molecule protein binders in live cells.

PMID- 30108796
TI  - Small structural changes of the imidazopyridine diacylglycerol acyltransferase 2
      (DGAT2) inhibitors produce an improved safety profile.
AB  - Small molecule DGAT2 inhibitors have shown promise for the treatment of metabolic
      diseases in preclinical models. Herein, we report the first toxicological
      evaluation of imidazopyridine-based DGAT2 inhibitors and show that the
      arteriopathy associated with imidazopyridine 1 can be mitigated with small
      structural modifications, and is thus not mechanism related.

PMID- 30108799
TI  - The structure-guided discovery of osimertinib: the first U.S. FDA approved mutant
      selective inhibitor of EGFR T790M.
AB  - The winners of the Malcolm Campbell Memorial Prize for 2017 discuss the structure
      guided discovery of Osimertinib and the difficulties associated with discovering
      a new drug.

PMID- 30108798
TI  - The discovery of a pan-genotypic, primer grip inhibitor of HCV NS5B polymerase.
AB  - The development of a series of novel 7-azabenzofurans exhibiting pan-genotype
      inhibition of HCV NS5B polymerase via binding to the primer grip site is
      presented. Many challenges, including poor oral bioavailability, high clearance,
      bioactivation, high human serum shift, and metabolic stability were encountered
      and overcome through SAR studies. This work culminated in the selection of BMS
      986139 (43) as a preclinical candidate.

PMID- 30108800
TI  - Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) and its inhibitors.
AB  - Ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1, EC 3.1.4.1) is a
      metalloenzyme that belongs to the NPP family, which comprises seven subtypes
      (NPP1-7). NPP1 hydrolyzes a wide range of phosphodiester bonds, e.g. in
      nucleoside triphosphates, (cyclic) dinucleotides, and nucleotide sugars yielding
      nucleoside 5'-monophosphates as products. Its main substrate is ATP which is
      cleaved to AMP and diphosphate. The enzyme is involved in various biological
      processes including bone mineralization, soft-tissue calcification, insulin
      receptor signalling, cancer cell proliferation and immune modulation. Therefore,
      NPP1 inhibitors have potential as novel drugs, e.g. for (immuno)oncology. In the
      last two decades several inhibitors of NPP1 derived from nucleotide- or non
      nucleotide scaffolds have been developed. The most potent and selective NPP1
      inhibitory substrate analog is adenosine 5'-alpha,beta-methylene-gamma
      thiotriphosphate (Ki = 20 nM vs. p-Nph-5'-TMP, human membrane-bound NPP1). Non
      nucleotide-derived NPP1 inhibitors comprise polysulfonates, polysaccharides,
      polyoxometalates and small heterocyclic compounds. The polyoxometalate
      [TiW11CoO40]8- (PSB-POM141) is the most potent and selective NPP1 inhibitor
      described to date (Ki = 1.46 nM vs. ATP, human soluble NPP1); it displays an
      allosteric mechanism of inhibition and represents a useful pharmacological tool
      for evaluating the potential of NPP1 as a novel drug target.

PMID- 30108801
TI  - New tricks for human farnesyltransferase inhibitor: cancer and beyond.
AB  - Human protein farnesyltransferase (FTase) catalyzes the addition of a C15
      farnesyl lipid group to the cysteine residue located in the COOH-terminal
      tetrapeptide motif of a variety of important substrate proteins, including well
      known Ras protein superfamily. The farnesylation of Ras protein is required both
      for its normal physiological function, and for the transforming capacity of its
      oncogenic mutants. Over the last several decades, FTase inhibitors (FTIs) were
      developed to disrupt the farnesylation of oncogenic Ras as anti-cancer agents,
      and some of them have entered cancer clinical investigation. On the other hand,
      some substrates of FTase were demonstrated to be related with other human
      diseases, including Hutchinson-Gilford progeria syndrome, chronic hepatitis D,
      and cardiovascular diseases. In this review, we summarize the roles of FTase in
      malignant transformation, proliferation, apoptosis, angiogenesis, and metastasis
      of tumor cells, and the recently anticancer clinical research advances of FTIs.
      The therapeutic prospect of FTIs on several other human diseases is also
      discussed.

PMID- 30108802
TI  - Mapping neuroreceptors with metal-labeled radiopharmaceuticals.
AB  - The growing epidemiological and economic burden of neurological diseases on
      society is tremendous. A correct and timely diagnosis can help in lowering the
      burden and improving the life quality of both the diseased person and the
      caretaker. Imaging of the brain (neuroimaging) using CT, MRI, and nuclear imaging
      methods can provide anatomical and functional information. Neuroreceptors are
      central to neurotransmission and neuromodulation in the CNS. In vivo imaging of
      receptors in the brain provides powerful tools for the functional study of the
      central nervous system (CNS) in normal or diseased states. Presently, PET imaging
      using non-metallic radiotracers dominates the imaging of neuroreceptors. Metal
      based probes for SPECT and PET can be economical and logistically easier to use
      without compromising the information. This review focuses on the development of
      metallic radiotracers for (99mTc) SPECT and (68Ga) PET along with future
      directions based on the metallic probes developed for other imaging modalities
      namely MRI.

PMID- 30108804
TI  - Exploring the links between peptoid antibacterial activity and toxicity.
AB  - Peptoids are a promising class of antimicrobial agents with reported activities
      against a range of both Gram-positive and Gram-negative bacteria, fungi and most
      recently parasites. However, at present the available toxicity data is somewhat
      limited and as such rationally designing effective antimicrobial peptoids can be
      challenging. Herein, we present the toxicity profiling of a series of linear
      peptoids against mammalian cell lines (HaCaT and HepG2). The cytotoxicity of the
      peptoid library has then been correlated with their antibacterial properties
      against Gram-positive and Gram-negative bacteria and also to the hydrophobicity
      of the peptoid sequences. The work presented provides valuable data to aid in the
      future rational design of antimicrobial peptoids.

PMID- 30108805
TI  - Recent trends in smart and flexible three-dimensional cross-linked polymers:
      synthesis of chitosan-ZnO nanocomposite hydrogels for insulin drug delivery.
AB  - One set of major challenges and significant progress is attributed to the
      discovery of novel pharmaceuticals from the exoskeleton of marine crustacean
      wastes to minimize the environmental pollutants. In this strategy, high molecular
      weight chitosan was subsequently used in the synthesis of smart three-dimensional
      cross-linked network polymers. Super absorbent chitosan-ZnO nanocomposite
      hydrogels were synthesized via a terminated diisocyanate compound, a chitosan
      sample (NH2/NCO), and ZnO nanoparticles in different concentrations (1-7%). The
      discovered intelligent drugs were confirmed by spectral analyses such as FTIR,
      XRD, DLS, TGA and morphological analyses such as AFM, SEM, and TEM. The unique
      physical properties of chitosan-ZnO nanocomposite hydrogels towards environmental
      stimuli and the porosity of their structures have gained particular interest in
      fluorescence isothiocyanate-labeled insulin-loaded hydrogel nanocomposites for in
      vivo drug delivery into the rat nasal cavity. Confocal laser scanning microscopy
      (CLSM) was used to prove the absorption enhancement of fluorescein isothiocyanate
      (FITC)-labeled insulin-loaded hydrogels in the rat nasal cavity by this
      formulation. The formulation of hydrogels apparently decreased the blood glucose
      concentration (50-65% of initial blood glucose concentration) for at least 4-5.5
      h after administration, and no apparent cytotoxicity was found after
      administration.

PMID- 30108803
TI  - An insight into the therapeutic potential of quinazoline derivatives as
      anticancer agents.
AB  - Cancer is one of the major causes of worldwide human mortality. A wide range of
      cytotoxic drugs are available on the market, and several compounds are in
      different phases of clinical trials. Many studies suggest that these cytotoxic
      molecules are also associated with different types of adverse side effects;
      therefore researchers around the globe are involved in the development of more
      efficient and safer anticancer drugs. In recent years, quinazoline and its
      derivatives have been considered as a novel class of cancer chemotherapeutic
      agents that show promising activity against different tumors. The aim of this
      article is to comprehensively review and highlight the recent developments
      concerning the anticancer activity of quinazoline derivatives as well as offer
      perspectives on the development of novel quinazoline derivatives as anticancer
      agents in the near future.

PMID- 30108807
TI  - Protection effect of intracellular melanin from Lachnum YM156 and Haikunshenxi
      capsule combination on adenine-induced chronic renal failure in mice.
AB  - This study aimed to elucidate the therapeutic effects of oral administration of
      intracellular melanin from Lachnum YM156 (LIM) on chronic renal failure (CRF) in
      mice. The cytotoxicity of LIM was evaluated using the 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) assay. CRF was induced in mice by
      chronic dietary adenine intake. We have used this intervention to explore the
      effects of oral treatment with LIM (100 and 200 mg kg-1) in CRF mice. The
      treatment with LIM alone and a combination of Haikunshenxi capsule (HC) add LIM
      increased the concentration levels of superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GSH-PX), and glutathione reductase (GSH), reduced
      malonaldehyde (MDA) in the nephridial tissues and also reduced the nephridial
      levels of tumor necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), and
      interleukin (IL)-6, and the activities of inducible nitric oxide synthase (iNOS).
      Interestingly, the HC and LIM combination produced a higher therapeutic effect
      than HC alone. The mechanism of the reported salutary effects of LIM in adenine
      induced CRF is associated with amelioration of the adenine induced inflammation
      and oxidative stress. The present findings recommend that LIM is a useful natural
      product which can be used to enhance the protection function of HC in CRF mice.

PMID- 30108808
TI  - 2-Arylaminobenzothiazole-arylpropenone conjugates as tubulin polymerization
      inhibitors.
AB  - A new series of 2-arylaminobenzothiazole-arylpropenone conjugates 5-6(a-r) was
      designed, synthesized and investigated for their cytotoxic potency against the
      various human cancer cell lines. Most of these conjugates exhibited cytotoxic
      activity and inhibited in vitro tubulin polymerization effectively. Conjugates 5d
      and 6d cause cell cycle blocks in the G2/M phase in HeLa cells and treatments
      with 5d and 6d manifested increased mRNA and protein levels of the G2/M marker,
      cyclin B1. Immunocytochemistry revealed loss of intact microtubule structure in
      cells treated with 5d and 6d. Western blot analysis revealed that these
      conjugates accumulate more tubulin in the soluble fraction. Moreover, the
      triggering of apoptotic cell death after mitotic arrest was investigated by
      studying their effect on Hoechst staining, mitochondrial membrane potential, ROS
      generation.

PMID- 30108806
TI  - Design, synthesis and biological evaluation of novel Schiff base-bridged
      tetrahydroprotoberberine triazoles as a new type of potential antimicrobial
      agents.
AB  - A series of novel Schiff base-bridged tetrahydroprotoberberine (THPB) triazoles
      were designed, synthesized and characterized for the first time. Antimicrobial
      assay showed that some of the prepared compounds exerted stronger antibacterial
      and antifungal activities than the reference drugs. Especially, THPB triazole 7a
      gave low MIC values of 0.5, 1 and 2 MUg mL-1 against B. yeast, M. luteus and
      MRSA, respectively. Further experiments indicated that the highly active molecule
      7a was able to rapidly kill the MRSA strain and did not trigger the development
      of bacterial resistance even after 14 passages. The preliminary exploration for
      the antimicrobial mechanism revealed that compound 7a could effectively
      intercalate into calf thymus DNA to form a 7a-DNA supramolecular complex, and its
      Zn2+ complex had the ability to directly cleave pUC19 DNA, which suggested that
      compound 7a might be a potentially dual-targeting antibacterial molecule. It was
      also found that compound 7a could be efficiently stored and carried by human
      serum albumin (HSA), and the hydrophobic interactions and hydrogen bonds played
      important roles in the transportation of HSA to the active molecule 7a.

PMID- 30108809
TI  - Synthesis and biological evaluation of N-alkyl naphthoimidazoles derived from
      beta-lapachone against Trypanosoma cruzi bloodstream trypomastigotes.
AB  - The QSAR study of 34 2-aryl-naphthoimidazoles screened so far revealed that
      sigmai is the most important factor for their lytic activity on the bloodstream
      trypomastigote forms of T. cruzi, the etiologic agent of Chagas disease. Based on
      this result, 16 new N-alkyl-naphthoimidazoles derived from 6,6-dimethyl-3,4,5,6
      tetrahydrobenzo[7,8]chromene[5,6-d]imidazole (the product of the reaction of beta
      lapachone with paraformaldehyde) by its reaction with halo-alkanes were prepared
      and evaluated against the parasite and peritoneal macrophages. The N1-n-hexyl and
      N3-n-hexyl naphthoimidazoles were 2.2 and 3.2 times more active than the standard
      drug benznidazole with selectivity indices of 2.7 and 13.4, respectively.

PMID- 30108810
TI  - Synthesis and in vitro study of novel borneol derivatives as potent inhibitors of
      the influenza A virus.
AB  - Herein, we present the design and synthesis of a series of novel heterocyclic
      derivatives of (-)-borneol and (-)-isoborneol as potent inhibitors of the
      influenza A virus. All compounds were tested for their toxicity against MDCK
      cells and for virus-inhibiting activity against the influenza virus A/Puerto
      Rico/8/34 (H1N1). Compounds 7, 16 and 26 containing a morpholine fragment
      exhibited the highest efficiency as agents inhibiting the replication of the
      influenza virus A(H1N1) with selectivity indices of 82, 45 and 65,
      correspondingly. Derivatives 9 (SI = 23) and 18 (SI = 25) containing a 1
      methylpiperazine motif showed moderate antiviral activity. Structure-activity
      analysis of this new series of borneol derivatives revealed that a 1,7,7
      trimethylbicyclo[2.2.1]heptan scaffold is required for the antiviral activity.

PMID- 30108811
TI  - Hypoglycemic and hypolipidemic effects of a polysaccharide from Lachnum YM240 and
      its derivatives in mice, induced by a high fat diet and low dose STZ.
AB  - Carboxymethylated and sulfated polysaccharides (CLEP and SLEP) were prepared from
      an exopolysaccharide previously obtained from Lachnum YM240 (LEP) by chemical
      modifications. Two doses (50 mg kg-1 and 200 mg kg-1 b. w.) of LEP, CLEP and SLEP
      were orally administered to normal mice and type 2 diabetic mice (T2DM) that were
      induced by streptozotocin (STZ) and a high fat diet, respectively. The
      hypoglycemic effect was evaluated by testing the oral glucose tolerance, fasting
      blood glucose (FBG) levels, fasting serum insulin (FINS), glycosylated hemoglobin
      A1c (HbA1c), and the hypolipidemic effect was evaluated by the body, spleen,
      pancreas, liver and kidney weights, as well as serum triglycerides (TG),
      cholesterol (TC) and free fatty acids (FFA). After four weeks of administration,
      LEP, CLEP and SLEP showed a marked FBG fall rate of 11.2%, 44.0% and 42.5% for
      the high-dose and 7.43%, 38.5% and 33.1% for the low-dose, respectively, as
      compared to the DC group. Moreover, compared with DC mice, TC concentrations in
      the high-dose groups of LEP, CLEP and SLEP were significantly decreased by 29.6%,
      38.7% (P < 0.05), 33.0% (P < 0.05), and TG concentrations decreased by 18.9%,
      43.9% (P < 0.01), 29.0% (P < 0.05), respectively. In addition, LEP and the
      derivatives significantly upregulated the expression of glucokinase (GK) and
      adenosine monophosphate-activated protein kinase (AMPK) in the liver, AMPK and
      glucose transporter 4 (Glut4) in skeletal muscle and peroxysome proliferator
      activated receptor (PPAR-gamma) in adipose tissue, whereas downregulated the
      expression of glucose-6-phosphatase (G6P) in the liver; these were examined using
      ELISA detection kits. These results for FBG and serum lipids indicate that LEP
      and its derivatives possess significant hypoglycemic and hypolipidemic effects
      and carboxymethylation improved the hypoglycemic and hypolipidemic effects more
      effectively than sulfation. Therefore, the carboxymethylated and sulfated
      modifications were effective ways to enhance the hypoglycemic and hypolipidemic
      activities of polysaccharides.

PMID- 30108812
TI  - Do GluN2B subunit containing NMDA receptors tolerate a fluorine atom in the
      phenylalkyl side chain?
AB  - The influence of an F-atom in the side chain of benzo[7]annulen-7-amines on the
      affinity towards GluN2B subunit containing NMDA receptors and the selectivity
      over related receptors was investigated. The synthesis of 5a and 5b was performed
      by reductive amination of the ketone 6 with primary alkanamines 14a and 14b
      bearing an F-atom in beta-position. The GluN2B affinities of non-fluorinated and
      fluorinated ligands 4 and 5 are almost identical. The low impact of the F-atom on
      GluN2B affinity was unexpected, as it influences several chemical and
      physicochemical properties of the ligands. However, introduction of the F-atom
      led to reduced selectivity over sigma receptors. Whereas 5a and 5b display still
      a 2-3-fold preference for GluN2B over sigma1 receptors, they show almost the same
      affinity to GluN2B and sigma2 receptors.

PMID- 30108813
TI  - Chiral disubstituted piperidinyl ureas: a class of dual diacylglycerol lipase
      alpha and ABHD6 inhibitors.
AB  - Inhibitors of diacylglycerol lipases and alpha,beta-hydrolase domain containing
      protein 6 (ABHD6) are potential leads for the development of therapeutic agents
      for metabolic and neurodegenerative disorders. Here, we report the
      enantioselective synthesis and structure activity relationships of triazole ureas
      featuring chiral, hydroxylated 2-benzylpiperidines as dual inhibitors of
      DAGLalpha and ABHD6. The chirality of the carbon bearing the C2 substituent, as
      well as the position of the hydroxyl (tolerated at C5, but not at C3) has
      profound influence on the inhibitory activity of both DAGLalpha and ABHD6, as
      established using biochemical assays and competitive activity-based protein
      profiling on mouse brain extracts.

PMID- 30108814
TI  - Novel 1,2,3-triazolium-based dicationic amphiphiles synthesized using click
      chemistry approach for efficient plasmid delivery.
AB  - Herein, we report the synthesis, characterization and evaluation of the
      transfection efficiencies of a series of dicationic amphiphiles designed to
      construct quaternary ammonium ion-based cationic lipids varying in chain length
      of the hydrophobic back bone connected individually through head group to a 1,2,3
      triazolium cation consisting of 2-hydroxy ethyl chain as substitution.
      Accordingly, three dicationic amphiphiles were synthesized by "click chemistry"
      approach and formulated to bilayered vesicles using DOPE as a co-lipid. The
      transfection efficacies of these novel lipid formulations were measured and
      correlated with the results obtained from various physicochemical techniques.
      Importantly, the observed gradient in the activity profile, where the
      transfection potential increased with decreasing chain length of the lipid
      hydrophobic back bone, highlights the synergistic interplay of the lipid alkyl
      chain length in coordination with charge delocalization in modulating the
      transfection potency of these 1,2,3-triazolium-based lipids.

PMID- 30108815
TI  - Design, synthesis and biological evaluation of imidazopyridine-propenone
      conjugates as potent tubulin inhibitors.
AB  - A library of imidazopyridine-propenone conjugates (8a-8u) were synthesized and
      evaluated for their antitumor activity against four human cancer cell lines,
      namely, prostate (DU-145), lung (A549), cervical (Hela) and breast (MCF-7) cancer
      cell lines. These conjugates showed good to moderate activity against the tested
      cell lines. Among them, two conjugates (8m and 8q) showed significant
      antiproliferative activity against the human lung cancer cell line (A549) with
      IC50 values of 0.86 MUM and 0.93 MUM, respectively. Flow cytometry analysis
      revealed that these compounds arrested the cell cycle at the G2/M phase in the
      human lung cancer cell line (A549), inhibiting tubulin polymerization leading to
      apoptosis. Further, Hoechst staining, decrease in mitochondrial membrane
      potential and Annexin V-FITC assay suggested that the cell death was due to
      apoptosis induction. Overall, the present investigation demonstrated that the
      synthesized imidazopyridine-propenone conjugates are promising tubulin inhibitors
      and apoptotic inducers.

PMID- 30108816
TI  - Design, synthesis, crystal structure and fungicidal activity of (E)-5
      (methoxyimino)-3,5-dihydrobenzo[e][1,2]oxazepin-4(1H)-one analogues.
AB  - A practical method of four-step synthesis towards novel (E)-5-(methoxyimino)-3,5
      dihydrobenzo[e][1,2]oxazepin-4(1H)-one antifungals is presented, where a
      commercially available pesticide and pharmacology intermediate, (E)-methyl 2-(2
      (bromomethyl)phenyl)-2-(methoxyimino)acetate (1), was used as starting material.
      These compounds were confirmed by 1H NMR, 13C NMR, high-resolution mass
      spectroscopy and X-ray crystal structure. Via in vitro fungicidal evaluation, the
      moderate to high activities of several compounds against eight phytopathogenic
      fungi were demonstrated. Especially, the fungicidal activities of compounds 5-03
      and 5-09 were comparable to those of the controls azoxystrobin and
      trifloxystrobin in precise virulence measurements for four fungi. These results
      suggested that dihydrobenzo[e][1,2]oxazepin-4(1H)-one analogues could be
      considered as potential fungicidal candidates for crop protection.

PMID- 30108817
TI  - 3D proteochemometrics: using three-dimensional information of proteins and
      ligands to address aspects of the selectivity of serine proteases.
AB  - The high similarity between certain sub-pockets of serine proteases may lead to
      low selectivity of protease inhibitors. Therefore the application of
      proteochemometrics (PCM), which quantifies the relationship between
      protein/ligand descriptors and affinity for multiple ligands and targets
      simultaneously, is useful to understand and improve the selectivity profiles of
      potential inhibitors. In this study, protein field-based PCM that uses knowledge
      based and WaterMap derived fields to describe proteins in combination with 2D
      (RDKit and MOE fingerprints) and 3D (4 point pharmacophoric fingerprints and
      GRIND) ligand descriptors was used to model the bioactivities of 24 homologous
      serine proteases and 5863 inhibitors in an integrated fashion. Of the multiple
      field-based PCM models generated based on different ligand descriptors, RDKit
      fingerprints showed the best performance in terms of external prediction with
      Rtest2 of 0.72 and RMSEP of 0.81. Further, visual interpretation of the models
      highlights sub-pocket specific regions that influence affinity and selectivity of
      serine protease inhibitors.

PMID- 30108818
TI  - Upconversion fluorescent and X-ray-sensitive bifunctional nanoprobes for
      assessing the penetrability of inorganic nanoparticles in the digestive system.
AB  - Nanotechnology is receiving increasing attention due to its fantastic advantages
      and potential applications in nanofood and nanomedicine. However, the safety of
      touching manufactured nanoparticles is still uncertain for human beings. Here, we
      track inorganic nanoparticles in the digestive system of the mouse through
      upconversion fluorescence and X-ray imaging, and try to demonstrate whether or
      not the inorganic nanoparticles will penetrate the digestive system to enter the
      blood system. Lanthanide-doped upconversion nanoparticles, which can convert
      infrared light to visible light and are simultaneously sensitive to X-rays, were
      selected as model inorganic nanoparticles. The investigation clarifies that even
      the ultrathin nanoparticles (~5 nm) could not penetrate the digestive tract to
      enter the bloodstream or surrounding tissues, but were gradually excreted out.
      Our results help assess the safety of inorganic nanoparticles potentially used in
      nanofood and nanomedicine.

PMID- 30108819
TI  - Synthesis, characterization, and radioprotective activity of alpha,beta
      unsaturated aryl sulfone analogs and their Tempol conjugates.
AB  - Some novel alpha,beta-unsaturated aromatic sulfone analogs (5a-5m) and their
      Tempol conjugates (6a-6e) have been synthetically prepared, characterized and
      evaluated for their radioprotective activity under gamma-ray radiation. The
      Tempol conjugates were characterized by X-ray single crystal diffraction. In
      vitro studies showed that 5a, 5b and 6b had superior activities to Ex-Rad pre
      treated before 5 Gy irradiation, and 5a, 6a and 6b had better activities than Ex
      Rad after 5 Gy irradiation, while 5a, 6a and 6b exhibited both prophylactic and
      mitigation effects, indicating the advantage of combining alpha,beta-unsaturated
      aromatic sulfones with Tempol nitroxide. Both p53 and phospho-p53 levels were
      significantly lower in compound-treated cells than those in untreated irradiated
      cells. The conjugates offer an improved radioprotective ability, which is an
      advantage in the treatment protocol.

PMID- 30108820
TI  - Synthesis and synergistic antifungal effects of monoketone derivatives of
      curcumin against fluconazole-resistant Candida spp.
AB  - Twenty-three monoketone derivatives of curcumin were synthesized to investigate
      the synergy with fluconazole against fluconazole-resistant Candida spp. The
      minimal inhibitory concentration (MIC80) and the fractional inhibitory
      concentration index (FICI) of the antifungal synergist fluconazole were measured
      against fluconazole-resistant C. albicans, C. tropicalis and C. krusei in vitro.
      Most of these compounds showed good synergistic activities against C. tropicalis.
      Among them, compound 9 exhibited significant synergistic activities against
      Candida spp. SARs were also discussed. In particular, a cell growth test
      exhibited that a combination of 1 MUg ml-1 fluconazole and 64 MUg ml-1 or 128 MUg
      ml-1 compound 9 showed the most potent fungicidal effect against C. tropicalis.
      The synergistic effect may be associated with the changes of the intracellular
      ATP content and cell membrane permeability. Our results provided a basis for
      future evaluation and development of these compounds as leads for therapeutics
      for fluconazole-resistant candidiasis.

PMID- 30108821
TI  - Regression of murine Ehrlich ascites carcinoma using synthesized cobalt complex.
AB  - Cisplatin as a chief chemotherapy has nephro-toxicity and so we have tried to
      develop a novel antitumor drug based on a combination of cobalt metal ion with an
      organic moiety. The antitumor activity of the complex was tested in vitro and in
      vivo against murine Ehrlich ascites carcinoma (EAC). Antioxidant capacity and
      nucleic acids content were determined. Cobalt(ii) diacetyl monoxime-2
      hydrazinopyridine complex significantly diminished tumor load. It decreased the
      tumor proliferation rate and obviously increased the life span of EAC-bearing
      mice. It reversed the haematological parameters back towards normal, reduced
      liver enzymes and urea, and increased albumin and total protein. Antioxidant
      parameters levels were reversed towards normal. An assessment was conducted by
      comparing these results with those obtained using the standard drug, cisplatin.
      The results suggest that the cobalt complex can be considered as a potent
      anticancer agent as it showed appreciable antitumor activity in EAC-bearing mice
      that was almost analogous to that of the reference standard, cisplatin.

PMID- 30108822
TI  - Effects of guanidino modified aminoglycosides on mammalian membranes studied
      using a quartz crystal microbalance.
AB  - The increase in bacterial and viral resistance to current therapeutics has led to
      intensive research for new antibacterial and antiviral agents. Among these,
      aminoglycosides and their guanidino derivatives are potent candidates targeting
      specific RNA sequences. It is necessary that these substances can pass across
      mammalian membranes in order to reach their intracellular targets. This study
      investigated the effects of the aminoglycosides kanamycin A and neomycin B and
      their guanidino derivatives on mammalian mimetic membranes using a quartz crystal
      microbalance with dissipation monitoring (QCM-D). Lipid bilayers as membrane
      models were deposited onto gold coated quartz crystals and aminoglycosides added
      afterwards. Notably, the guanidino derivatives exhibited an initial stiffening of
      the membrane layer indicating a quick insertion of the planar guanidino groups
      into the membrane. The guanidino derivatives also reached their maximum binding
      to the membrane at lower concentrations than the native compounds. Therefore,
      these modified aminoglycosides are promising agents for the development of new
      antimicrobial treatments.

PMID- 30108823
TI  - Insight into the complete substrate-binding pocket of ThiT by chemical and
      genetic mutations.
AB  - Energy-coupling factor (ECF) transporters are involved in the uptake of
      micronutrients in bacteria. The transporters capture the substrate by high
      affinity binding proteins, the so-called S-components. Here, we present the
      analysis of two regions of the substrate-binding pocket of the thiamine-specific
      S-component in Lactococcus lactis, ThiT. First, interaction of the thiazolium
      ring of thiamine with residues Trp34, His125 and Glu84 by pi-pi-stacking and
      cation-pi is studied, and second, the part of the binding pocket that extends
      from the hydroxyl group. We mutated either the transported ligand (chemically) or
      the protein (genetically). Surprisingly, modifications in the thiazolium ring by
      introducing substituents with opposite electronic effects had similar effects on
      the binding affinity. We hypothesize that the electronic effects are superseeded
      by steric effects of the added substituents, which renders the study of isolated
      interactions difficult. Amino acid substitutions in ThiT indicate that the
      electrostatic interaction facilitated by residue Glu84 of ThiT and thiamine is
      necessary for picomolar affinity. Deazathiamine derivatives that explore the
      subpocket of the binding site extending from the hydroxyl group of thiamine bind
      with high affinity to ThiT and may be developed into selective inhibitors of
      thiamine transport by ECF transporters. Molecular-dynamics simulations suggest
      that two of these derivatives may not only bind to ThiT, but could also be
      transported.

PMID- 30108825
TI  - Identification of steroid-like natural products as antiplasmodial agents by 2D
      and 3D similarity-based virtual screening.
AB  - The emergence of drug resistance in Plasmodium falciparum to available
      antimalarial drugs has challenged current antimalarial treatments. New
      antimalarials, particularly those with novel mechanisms of action and no cross
      resistance to current drugs, are therefore urgently needed. To identify new
      growth inhibitors of Plasmodium falciparum, 2D and 3D similarity-based virtual
      screening methods were employed in parallel with an in-house database of steroid
      type natural products using fusidic acid as a search query. The resulting hit
      compounds were further filtered based on the predicted partition coefficient, log
      P. The virtual screening strategy resulted in the identification of nine new
      compounds that inhibited parasite growth with IC50 values of <20 MUM. Four
      compounds exhibited IC50 values in the range of 1.39-3.45 MUM and three of which
      showed a promising selectivity index. Further, the predicted ADME properties of
      the four most active compounds were found to be comparable to fusidic acid. These
      compounds can be further explored using structural modifications in the
      identification and development of more potent parasite growth inhibitors with
      improved selectivity.

PMID- 30108824
TI  - High throughput methods to measure the propensity of compounds to form
      intramolecular hydrogen bonding.
AB  - Implementation of IMHB considerations in drug discovery needs robust and
      validated descriptors to experimentally verify the propensity of compounds to
      exhibit IMHBs. The first part of the paper presents an overview of the most
      common techniques to measure the propensity of compounds to form IMHBs. Then we
      review and discuss recently proposed high throughput (HT) physicochemical
      descriptors (i.e. Deltalog Poct-tol, EPSA and log k'80 PLRP-S) which provide the
      same information. Analysis of the available data enabled us to extract guidelines
      for the application of these descriptors in drug discovery programs.

PMID- 30108826
TI  - Design, synthesis and pharmacological evaluation of new 2-oxo-quinoline
      derivatives containing alpha-aminophosphonates as potential antitumor agents.
AB  - A series of novel 2-oxo-quinoline derivatives containing alpha-aminophosphonates
      were designed and synthesized as antitumor agents. MTT (3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide) assay results demonstrated that some
      compounds exhibited moderate to high inhibitory activity against HepG2, SK-OV-3
      and NCI-H460 tumor cell lines, and most compounds showed much lower cytotoxicity
      against HL-7702 normal cells than 5-FU and cisplatin. The action mechanism of
      representative compound 5b was investigated by fluorescence staining assay, flow
      cytometric analysis and western blot (WB) assay, which indicated that this
      compound induced apoptosis and G2/M phase arrest accompanied by an increase in
      the production of intracellular Ca2+ and reactive oxygen species (ROS) and
      affecting associated enzymes and genes.

PMID- 30108827
TI  - Synthesis of benzo[d]thiazole-hydrazone analogues: molecular docking and SAR
      studies of potential H+/K+ ATPase inhibitors and anti-inflammatory agents.
AB  - A series of new benzo[d]thiazole-hydrazones were synthesized and characterized by
      analytical and spectroscopic techniques. All the compounds were screened for
      their in vitro inhibition of H+/K+ ATPase and anti-inflammatory effects. The
      results revealed that compounds 6-8, 13-15, 18-20, 22, 23 and 27-30 displayed
      excellent inhibitory activity against H+/K+ ATPase, and their IC50 values were
      lower than those of the standard compound omeprazole. Compounds 2-5, 9-12, 28 and
      30 exhibited better anti-inflammatory activity in comparison to the standard
      compound indomethacin. Studies of the structure-activity relationship (SAR)
      showed that electron-donating groups (OH and OCH3) favored inhibitory activity
      against H+/K+ ATPase, whereas electron-withdrawing groups (F, Cl, Br and NO2)
      favored anti-inflammatory activity, and derivatives with both electron-donating
      (OH and OCH3) and electron-withdrawing (Br) groups (16-18) displayed reasonable
      activity, whereas aliphatic analogues (24-26) exhibited less activity and
      heterocyclic analogues (27-30) displayed moderate activity in both biological
      studies. Molecular docking studies were performed for all the synthesized
      compounds, among which compounds 19 and 20 exhibited the highest docking scores
      for inhibitory activity against H+/K+ ATPase, whereas compounds 10 and 12
      displayed the highest docking scores for anti-inflammatory activity.

PMID- 30108828
TI  - Design of a ligand for cancer imaging with long blood circulation and an enhanced
      accumulation ability in tumors.
AB  - The use of imaging agents to visualize tumor cells is an advantageous technique
      to achieve a more efficient intraoperative diagnosis and effective debulking
      operations. Targeting of these agents to certain receptors that are overexpressed
      in cancer cells, such as the folate receptor, aids in tumor targeting. Several
      imaging probes have been developed using this strategy. However, these ligand
      targeting cancer imaging probes are rapidly cleared during systemic delivery due
      to their small size, which compromises their biodistribution and circulation.
      Improving the detection of cancer requires higher accumulation and effective
      retention activities of imaging probes. Here we developed a new design for a
      folate-fluorophore conjugate that is modified with palmitoyl. Palmitic acid has a
      strong binding affinity with human serum albumin (HSA), which has the ability to
      form non-covalent host-guest complexes and has a blood half-life of 19 days. In
      this strategy, HSA is expected to serve as an endogenous nanocarrier for the
      designed probe in blood circulation. We hypothesized that via a reversible
      interaction with HSA, this simple palmitoyl modification on a folate-fluorophore
      conjugate can induce long blood circulation of the probe. Our folate-targeted
      probe could show longer blood circulation compared to the probe which lacks
      palmitoyl.

PMID- 30108830
TI  - Facilitating the presentation of antigen peptides on dendritic cells for cancer
      immunotherapy using a polymer-based synthetic receptor.
AB  - The introduction of proteins into dendritic cells (DCs) ex vivo is a critical
      step for the DC-based immunotherapy of cancer. Here, we developed a biotin
      modified polymer with multiple hydrophobic membrane anchors for cells that
      functions as a synthetic receptor for an antigen protein, ovalbumin (OVA), to
      introduce it efficiently into DCs compared with the conventional pulsing method.
      Our method showed significant advantages, including the rapid incorporation of
      OVA and the activation of antigen-specific T cells in a MHC-restricted manner.
      When mice were immunized by DCs treated with our method, tumor growth was
      completely suppressed, indicating that our method can be used to prepare adjuvant
      DCs.

PMID- 30108829
TI  - Development of 2-aminooxazoline 3-azaxanthene beta-amyloid cleaving enzyme (BACE)
      inhibitors with improved selectivity against Cathepsin D.
AB  - As part of an ongoing effort at Amgen to develop a disease-modifying therapy for
      Alzheimer's disease, we have previously used the aminooxazoline xanthene (AOX)
      scaffold to generate potent and orally efficacious BACE1 inhibitors. While AOX
      BACE1 inhibitors demonstrated acceptable cardiovascular safety margins, a retinal
      pathological finding in rat toxicological studies demanded further investigation.
      It has been widely postulated that such retinal toxicity might be related to off
      target inhibition of Cathepsin D (CatD), a closely related aspartyl protease. We
      report the development of AOX-BACE1 inhibitors with improved selectivity against
      CatD by following a structure- and property-based approach. Our efforts
      culminated in the discovery of a picolinamide-substituted 3-aza-AOX-BACE1
      inhibitor absent of retinal effects in an early screening rat toxicology study.

PMID- 30108832
TI  - PAIN-less identification and evaluation of small molecule inhibitors against
      protein tyrosine phosphatase 1B.
AB  - A highly miniaturized biochemical assay was set up to test a focused set of
      natural products against the enzymatic activity of protein tyrosine phosphatase
      1B (PTP1B). The screen resulted in the identification of the natural product
      alkaloids, berberine and palmatine as well as alpha-tocopheryl succinate (alpha
      TOS) as potential inhibitors of PTP1B. In a second step, several read-out and
      counter assays were applied to confirm the observed inhibitory activity of the
      identified hits and to remove false positives which target the enzymatic activity
      of PTP1B by a non-specific mechanism, also known as PAINS (pan-assay interference
      compounds). Both, berberine and palmatine were identified as false positives
      which interfered with the assay read-out. Using NMR spectroscopy, self
      association via stacking interactions was detected for berberine in aqueous
      media, which may also contribute to the non-specific inhibition of PTP1B. alpha
      TOS was confirmed as a novel reversible and competitive inhibitor of PTP1B. A
      concise structure-activity relationship study identified the carboxyl group and
      the saturated phytyl-side chain as being critical for PTP1B inhibition.

PMID- 30108831
TI  - Development of novel beta-carboline-based hydroxamate derivatives as HDAC
      inhibitors with DNA damage and apoptosis inducing abilities.
AB  - A series of novel beta-carboline-based hydroxamate derivatives (8a-n) as HDAC
      inhibitors have been designed and synthesized. Most of these compounds displayed
      potent histone deacetylase inhibitory effects and good antiproliferative activity
      with IC50s in the low micromolar range. One of the most potent compounds (8k)
      showed the strongest inhibition of the proliferation of human hepatocellular
      carcinoma (HCC) cells in vitro, with IC50 values lower than that of the currently
      approved HDAC inhibitor SAHA. Compound 8k also increased acetylation of histone
      H3 and alpha-tubulin, consistent with its potent HDAC inhibition. Importantly, 8k
      induced hypochromism by electrostatic interactions with CT-DNA, suggesting
      potential induction of DNA damage. Finally, 8k significantly induced HepG2 cell
      apoptosis by regulating apoptotic relative proteins expression. Together, our
      findings suggest that these novel beta-carboline-based hydroxamate derivatives
      may provide a new framework for the discovery of novel antitumor agents for the
      intervention of human carcinoma cells.

PMID- 30108833
TI  - In silico prediction of chemical subcellular localization via multi
      classification methods.
AB  - Chemical subcellular localization is closely related to drug distribution in the
      body and hence important in drug discovery and design. Although many in vivo and
      in vitro methods have been developed, in silico methods play key roles in the
      prediction of chemical subcellular localization due to their low costs and high
      performance. For that purpose, machine learning-based methods were developed
      here. At first, 614 unique compounds localized in the lysosome, mitochondria,
      nucleus and plasma membrane were collected from the literature. 80% of the
      compounds were used to build the models and the rest as the external validation
      set. Both fingerprints and molecular descriptors were used to describe the
      molecules, and six machine learning methods were applied to build the multi
      classification models. The performance of the models was measured by 5-fold cross
      validation and external validation. We further detected key substructures for
      each localization and analyzed potential structure-localization relationships,
      which could be very helpful for molecular design and modification. The key
      substructures can also be used as features complementary to fingerprints to
      improve the performance of the models.

PMID- 30108834
TI  - Pyrazolo[3,4-d]pyrimidines as sigma-1 receptor ligands for the treatment of pain.
      Part 1: 4-acylamino derivatives.
AB  - The synthesis of a new series of 4-acylaminopyrazolo[3,4-d]pyrimidines active on
      the sigma-1 receptor (sigma1R) is reported. Compounds were efficiently prepared
      using a two to three step process starting from commercially available 1H
      pyrazolo[3,4-d]pyrimidin-4-amine. A SAR study shows that the sigma1R requires the
      presence of relatively highly lipophilic substituents at opposite sides of the
      central scaffold, while selectivity versus the sigma2R can be improved by
      shortening the distance of the basic nitrogen to it. Compound 9a was among the
      most active and selective in vitro derivatives and exhibited potent
      antinociceptive properties in several pain models in mice, indicating its
      antagonistic behaviour.

PMID- 30108835
TI  - Pyrazolo[3,4-d]pyrimidines as sigma-1 receptor ligands for the treatment of pain.
      Part 2: Introduction of cyclic substituents in position 4.
AB  - The replacement of acylamino by cyclic substituents in the position 4 of the
      pyrazolo[3,4-d]pyrimidine scaffold, led to highly active sigma-1 receptor
      (sigma1R) ligands. Phenyl or pyrazolyl groups were the best in terms of affinity
      for the sigma1R and the 4-(1-methylpyrazol-5-yl) derivative, 12f, was the most
      selective. Compound 12f is also one of the best sigma1R ligands ever described in
      terms of lipophilic ligand efficiency, which translates into a good
      physicochemical and ADMET profile. In addition, 12f was identified as an
      antagonist of the sigma1R in view of its potent antinociceptive profile in
      several pain models in mice.

PMID- 30108836
TI  - The discovery of a potent Nav1.3 inhibitor with good oral pharmacokinetics.
AB  - In this article, we describe the discovery of an aryl ether series of potent and
      selective Nav1.3 inhibitors. Based on structural analogy to a similar series of
      compounds we have previously shown bind to the domain IV voltage sensor region of
      Nav channels, we propose this series binds in the same location. We describe the
      development of this series from a published starting point, highlighting key
      selectivity and potency data, and several studies designed to validate Nav1.3 as
      a target for pain.

PMID- 30108837
TI  - Synthesis of thioether andrographolide derivatives and their inhibitory effect
      against cancer cells.
AB  - A series of novel thioether andrographolide derivatives were synthesized by
      incorporating various aromatic (or heteroaromatic) substituents into C-12 or 14
      OH. A total of 38 andrographolide derivatives were prepared and evaluated for
      their in vitro inhibitory activity against cancer cells. All the derivatives
      exhibited better activity against prostate cancer cells (PC-3) than the parent
      compound. Among these, compounds 6a, 8, 9, 17, 19, 31, and 32 demonstrated good
      activity. These compounds were further evaluated for their anticancer activities
      against other cancer cell lines including MCF-7, MDA-MB-231, and A549. Compounds
      31 and 32 showed excellent activity against MCF-7 with an IC50 value of 0.7 and
      0.6 MUM, respectively. The absolute configuration of 15a was determined via
      single-crystal X-ray diffraction. The activity of 6a (12S), which was the
      precursor of 15a, was better than that of the diastereoisomer 6b (12R). Moreover,
      the preliminary structure-activity relationship has been summarized. The results
      obtained herein are very important for further optimization of andrographolide.

PMID- 30108838
TI  - Ring-opened aminothienopyridazines as novel tau aggregation inhibitors.
AB  - Aminothienopyridazines (ATPZs) have demonstrated efficacy, in vitro, as tau
      protein aggregation inhibitors. Modifications were made to the ATPZ scaffold to
      determine the importance of certain structural features for activity. More
      specifically, ring-opened analogues detached at the nitrogen-nitrogen bond of the
      pyridazine, were synthesized and their inhibitory activity evaluated. Preliminary
      data suggests that the ring-opened structures retain inhibitory activity,
      independent of tau oxidation. The structures detailed represent the beginnings of
      a deconstruction-reconstruction-elaboration study, with the aim of identifying
      simpler scaffolds, which retain activity and can be optimized in terms of
      physiochemical properties.

PMID- 30108839
TI  - Interaction of indomethacin with calf thymus DNA: a multi-spectroscopic,
      thermodynamic and molecular modelling approach.
AB  - Indomethacin belongs to the acetic acid derivative class of non-steroidal anti
      inflammatory drugs with diverse pharmacological and biological activities.
      Understanding the mechanism of interaction of drugs with possible target and off
      target biomolecules can prove useful in the development of a rational drug
      designing system. In this paper, we have attempted to ascertain the mode of
      binding of indomethacin with calf thymus DNA (Ct-DNA) through various biophysical
      techniques and in silico molecular docking. Analysis of the UV-visible absorbance
      spectra and fluorescence emission profile of indomethacin upon addition of Ct-DNA
      indicates the formation of a drug-DNA complex. UV-visible absorbance and steady
      state fluorescence experiments revealed a binding constant on the order of 103 L
      mol-1, which is consistent with those of well-known groove binders. Competitive
      displacement studies with ethidium bromide, acridine orange and Hoechst 33258
      further suggested that indomethacin binds to the minor groove of the Ct-DNA. The
      above observations were further confirmed by KI induced quenching experiments,
      DNA melting studies, CD spectral analysis and viscosity measurements. The
      thermodynamic parameters like spontaneous free energy (DeltaG < 0) and large
      favourable enthalpy (DeltaH < 0) obtained from isothermal calorimetry indicated
      the involvement of hydrogen bonding and van der Waals forces in the binding
      process. Molecular docking further corroborated the experimental results.

PMID- 30108840
TI  - Synthesis, structure-activity relationship and binding mode analysis of 4
      thiazolidinone derivatives as novel inhibitors of human dihydroorotate
      dehydrogenase.
AB  - A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel
      human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31
      displayed IC50 values of 1.75 and 1.12 MUM, respectively. The structure-activity
      relationship was summarized. Further binding mode analysis revealed that compound
      31 could form a hydrogen bond with Tyr38 and a water-mediated hydrogen bond with
      Ala55, which may be necessary for maintaining the bioactivities of the compounds
      in this series. Further structural optimization of the para- or meta-position of
      the phenyl group at R will lead to the identification of more potent hDHODH
      inhibitors.

PMID- 30108841
TI  - Benzylsulfanyl benzo-heterocycle amides and hydrazones as new agents against drug
      susceptible and resistant Mycobacterium tuberculosis.
AB  - A series of benzylsulfanyl benzo-heterocycle amides and hydrazones were
      synthesized and evaluated for anti-tubercular activities. The isonicotinyl
      hydrazone derivatives 12d, 12e and 12f exhibited good anti-tubercular activity
      against Mycobacterium tuberculosis H37Rv (ATCC #27294) with MIC values of 0.23,
      0.24 and 0.24 MUM, respectively, and were also active against SDR-TB, MDR-TB and
      XDR-TB. More importantly, compound 12e also showed low cytotoxicity and good
      metabolic stability, and could significantly reduce the mycobacterial burden in a
      mouse model infected with autoluminescent H37Ra strain, which may serve as a lead
      compound for further development.

PMID- 30108843
TI  - Dichloro-naphthoquinone as a non-classical inhibitor of the mycobacterial
      carbonic anhydrase Rv3588c.
AB  - The soluble mycobacterial carbonic anhydrases Rv3588c and Rv1284 belong to a
      different class of carbonic anhydrases than those found in humans, making them
      attractive drug targets by using the inherent differences in the folds of the
      different classes. By screening a natural product library, we identified
      naphthoquinone derivatives as a novel non-classical inhibitor scaffold of
      mycobacterial carbonic anhydrases that lack the sulfonamide/sulfamate group and
      thus did not affect human carbonic anhydrase II.

PMID- 30108842
TI  - 5-Methyl-N-(8-(5,6,7,8-tetrahydroacridin-9-ylamino)octyl)-5H-indolo[2,3
      b]quinolin-11-amine: a highly potent human cholinesterase inhibitor.
AB  - The synthesis, cholinesterase inhibition, molecular modelling and ADME properties
      of novel tacrine-neocryptolepine heterodimers are described. Compound 3 [5-methyl
      N-(8-(5,6,7,8-tetrahydroacridin-9-ylamino)octyl)-5H-indolo[2,3-b]quinolin-11
      amine], showing a moderate inhibition of the Abeta1-42 self-aggregation (26.5% at
      a 1 : 5 ratio with Abeta1-42), and a calculated log BB value (0.27) indicating
      excellent potential BBB penetration, is a highly potent human cholinesterase
      inhibitor [IC50 (hAChE) = 0.95 +/- 0.04 nM; IC50 (hBuChE) = 2.29 +/- 0.14 nM]
      which can be listed among the most potent hAChE inhibitors so far identified, and
      is not hepatotoxic in vitro at the concentrations at which the ChEs are
      inhibited. A molecular modeling study was also undertaken in order to elucidate
      the AChE and the BuChE bind modes of all the new compounds. The docking results
      show that all of them bind to AChE in extended conformations and to BuChE in
      folded conformations. Moreover, these studies revealed that the length of the
      linker is crucial to binding both the catalytic anionic site and the peripheral
      anionic site.

PMID- 30108844
TI  - Discovery of novel trimethoxy-ring BRD4 bromodomain inhibitors: AlphaScreen
      assay, crystallography and cell-based assay.
AB  - As a member of the bromodomain and extra terminal domain (BET) protein family,
      BRD4 is closely related to cancers and other diseases. Small-molecule BRD4
      inhibitors have already demonstrated promising potential for the therapy of BRD4
      related cancers. In this study, we report the discovery and evaluation of a novel
      category of BRD4 inhibitors, which share a trimethoxy ring and target the first
      bromodomain of the human BRD4 protein. The IC50 value of the most potent
      compound, DC-BD-03, is 2.01 MUM. In addition, a high-resolution crystal structure
      of the compound DC-BD-29 with the first bromodomain of BRD4 was determined, which
      revealed the binding mode and facilitated further structure-based optimization.
      These compounds exhibited anti-proliferation activity, caused cell cycle arrest,
      and induced apoptosis in human leukemia MV4-11 cells. Thus, the results presented
      in this study indicated the potential of this series of compounds as drug
      candidates for the therapy of BRD4-related cancers.

PMID- 30108845
TI  - A structurally guided dissection-then-evolution strategy for ligand optimization
      of smoothened receptor.
AB  - We present herein a novel dissection-then-evolution strategy for ligand
      optimization. Using the co-crystal structure of the smoothened receptor (SMO) as
      a guide, we studied the modular contribution of LY2940680 by systematically
      "silencing" the specific interaction between the individual residue(s) and the
      fragment in the ligand. Following evolution by focusing on the benzoyl part
      finally yielded an improved ligand 21.

PMID- 30108846
TI  - Maltodextrin modified liposomes for drug delivery through the blood-brain
      barrier.
AB  - Central nervous system acting drugs, when administered intravenously, cannot show
      their effect in the brain due to the difficulty in crossing the blood-brain
      barrier (BBB). Levodopa is one of those drugs that are used to treat Parkinson's
      disease. In this study, a new liposomal levodopa delivery system that is modified
      with maltodextrin was developed in order to target and enhance transport through
      the BBB. An antioxidant, glutathione, was co-loaded in liposomes as a supportive
      agent and its effect on liposome stability and delivery was investigated.
      Glutathione co-loading had a positive effect on the viabilities of 3T3 and SH
      SY5Y cells. Maltodextrin targeted liposomes showed high in vitro levodopa passage
      in the parallel artificial membrane permeability assay and had superior binding
      to MDCK cells. Results suggest that maltodextrin modification of liposomes is an
      effective way of targeting the BBB and the developed liposomal formulation would
      improve brain delivery of central nervous system agents.

PMID- 30108848
TI  - Succinct synthesis of saturated hydroxy fatty acids and in vitro evaluation of
      all hydroxylauric acids on FFA1, FFA4 and GPR84.
AB  - Saturated hydroxy fatty acids make up a class of underexplored lipids with
      potentially interesting biological activities. We report a succinct and general
      synthetic route to saturated hydroxy fatty acids hydroxylated at position 6 or
      higher, and exemplify this with the synthesis of hydroxylauric acids. All
      regioisomers of hydroxylauric acids were tested on free fatty acid receptors
      FFA1, FFA4 and GPR84. The results show that the introduction of a hydroxy group
      and its position have a high impact on receptor activity.

PMID- 30108847
TI  - Novel bipharmacophoric inhibitors of the cholinesterases with affinity to the
      muscarinic receptors M1 and M2.
AB  - A set of hybrid compounds composed of the fragment of allosteric modulators of
      the muscarinic receptor, i.e. W84 and naphmethonium, and the well-known AChE
      inhibitor tacrine on the one hand, and the skeletons of the orthosteric
      muscarinic agonists, iperoxo and isox, on the other hand, were synthesized. The
      two molecular moieties were connected via a polymethylene linker of varying
      length. These bipharmacophoric compounds were investigated for inhibition of AChE
      (from electric eel) and BChE (from equine serum) as well as human ChEs in vitro
      and compared to previously synthesized dimeric inhibitors. Among the studied
      hybrids, compound 10-C10, characterized by a 10 carbon alkylene linker connecting
      tacrine and iperoxo, proved to be the most potent inhibitor with the highest
      pIC50 values of 9.81 (AChE from electric eel) and 8.75 (BChE from equine serum).
      Docking experiments with compounds 10-C10, 7b-C10, and 7a-C10 helped to interpret
      the experimental inhibitory power against AChE, which is affected by the nature
      of the allosteric molecular moiety, with the tacrine-containing hybrid being much
      more active than the naphthalimido- and phthalimido-containing analogs.
      Furthermore, the most active AChE inhibitors were found to have affinity to M1
      and M2 muscarinic receptors. Since 10-C10 showed almost no cytotoxicity, it
      emerged as a promising lead structure for the development of an anti-Alzheimer
      drug.

PMID- 30108849
TI  - Advances in indoleamine 2,3-dioxygenase 1 medicinal chemistry.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) mediates multiple immunoregulatory processes
      including the induction of regulatory T cell differentiation and activation,
      suppression of T cell immune responses and inhibition of dendritic cell function,
      which impair immune recognition of cancer cells and promote tumor growth. On this
      basis, this enzyme is widely recognized as a valuable drug target for the
      development of immunotherapeutic small molecules in oncology. Although medicinal
      chemistry has made a substantial contribution to the discovery of numerous
      chemical classes of potent IDO1 inhibitors in the past 20 years, only very few
      compounds have progressed in clinical trials. In this review, we provide an
      overview of the current understanding of structure-function relationships of the
      enzyme, and discuss structure-activity relationships of selected classes of
      inhibitors that have shaped the hitherto few successes of IDO1 medicinal
      chemistry. An outlook opinion is also given on trends in the design of next
      generation inhibitors of the enzyme.

PMID- 30108851
TI  - Adaptation of a bacterial membrane permeabilization assay for quantitative
      evaluation of benzalkonium chloride as a membrane-disrupting agent.
AB  - We describe the use of the ortho-nitrophenyl-beta-galactoside (ONPG) assay
      developed by Lehrer et al. to which a new mathematical data treatment was
      applied. In this simplified assay, only one enzymatic assay is needed to provide
      direct evidence of the kinetics of Escherichia coli membrane permeabilization
      induced by different concentrations of benzalkonium chloride (BAC). Analysis of
      the data obtained from the revised ONPG assay with our adapted mathematical
      formula indicates that BAC induces permeabilization of the bacterial outer and
      inner membranes in a two-step process. The two effective concentration (EC50)
      values obtained in this study, combined with the results from an outer membrane
      permeabilization assay, suggest that the two steps observed in the
      permeabilization process are related to the two different bacterial membranes. We
      show that membrane permeabilization occurs very fast upon the addition of
      bacterial cells to the BAC solutions and demonstrate that sub-lethal
      concentrations of BAC disturb the integrity of the Gram-negative bacterial
      membranes. Overall, our work broadens our knowledge on the mode of action of BAC
      on bacterial cells and emphasizes that BAC, and quaternary ammonium compounds in
      general, should not be used at sub-lethal concentrations in order to lower the
      risk of bacterial tolerance and resistance to antibiotics.

PMID- 30108852
TI  - Rational design and synthesis of novel phenylsulfonyl-benzamides as anti-prostate
      cancer agents.
AB  - Prostate cancer is a major cause of male death worldwide and the identification
      of new efficient treatments is constantly needed. Different non-steroidal
      androgen receptor antagonists are approved also in the case of castration
      resistant cancer forms. Using a rational approach and molecular modelling studies
      to modify the structure of antiandrogen drug bicalutamide, a new series of
      phenylsulfonyl-benzamide derivatives was designed and synthesised. Their
      antiproliferative activities were evaluated in four different human prostate
      cancer cell lines and several new compounds showed significantly improved IC50
      values in the low MUM range. The cytotoxicity profile was also evaluated for the
      novel structures in the HEK293 cell line.

PMID- 30108850
TI  - Recent progress in the development of metal complexes as beta-amyloid imaging
      probes in the brain.
AB  - In this review, we have focused on the recent progress in metal complexes that
      are able to bind to beta-amyloid (Abeta) species. We have discussed various
      radioactive complexes of 99mTc, 68Ga, 64Cu, 89Zr, and 111In, which were designed
      as Abeta imaging agents for positron emission tomography (PET) and single photon
      emission computed tomography (SPECT) imaging, non-radioactive Re and Ru complexes
      as Abeta sensors using luminescence methods, and Gd3+ complexes as contrast
      agents for magnetic resonance imaging (MRI).

PMID- 30108853
TI  - Side chain-functionalized aniline-derived ursolic acid derivatives as multidrug
      resistance reversers that block the nuclear factor-kappa B (NF-kappaB) pathway
      and cell proliferation.
AB  - A series of inhibitors of NF-kappaB based on ursolic acid (UA) derivatives
      containing functionalized aniline or amide side chains were synthesized and
      evaluated for inhibition of NF-kappaB as well as their antitumor effects. These
      compounds exhibited significant inhibition activity toward NF-kappaB with IC50
      values at micromolar concentrations in the NCI-H460 lung adenocarcinoma cell
      line. A docking study of the most active compound 5Y8 revealed key interactions
      between 5Y8 and the active site of NF-kappaB in which the functionalized amide
      moiety at the C-28 position and an ester group at the C-3 position were important
      for improving the activity. In particular, compound 5Y8 appeared to be the most
      potent compound against the NCI-H460 cell line, and displayed similar efficiency
      in drug-sensitive versus drug-resistant cancer cell lines, at least partly, by
      blocking the NF-kappaB signaling pathway and inducing apoptosis. Mechanistically,
      compound 5Y8 might trigger the apoptotic signaling pathway. Thus, the rational
      design of UA derivatives with functionalized aniline or amide side chains offers
      significant potential for the discovery of a new class of NF-kappaB inhibitors
      with the ability to induce apoptosis and reverse multidrug resistance in the NCI
      H460 lung adenocarcinoma cell line.

PMID- 30108854
TI  - Peptide-fluorophore/AuNP conjugate-based two-photon excited fluorescent
      nanosensor for caspase-3 activity imaging assay in living cells and tissue.
AB  - In the present study, a novel fluorescence resonance energy transfer (FRET)
      strategy-based two-photon excited nanosensor via the assembly of two-photon dye
      labeled peptides on the gold nanoparticle's surface has been developed and
      successfully applied in the caspase-3 imaging assay in living cells and ischemia
      reperfusion surgery-treated rat liver tissue slices.

PMID- 30108855
TI  - Design, facile synthesis and anthelmintic activity of new O-substituted 6
      methoxybenzothiazole-2-carbamates. Part II.
AB  - In the framework of pursuing the design and synthesis of a new series of
      substituted 6-methoxybenzothiazole-2-carbamates as potential anthelmintics, and
      as a continuation of the expended efforts in part I, we have set out to develop
      novel compounds with enhanced anthelmintic activity by blocking the 6-position of
      benzothiazole with side chains of different polarities. Guided by the findings in
      part I, and reporting the paramphistomicidal activity of oxadiazoline derivatives
      V and VI, we aimed to synthesize target benzothiazoles designed to comprise some
      planar heterocyclic ring systems, namely, 1,3,4-oxadiazoles and 1,2,4-triazoles,
      bearing a variety of hydrophobic and hydrophilic components. The synthesis of the
      desired compounds was primarily achieved by cyclization of 6-acetohydrazide, 1.
      The in vitro paramphistomicidal activity of all synthesized carbamates was
      evaluated. Four synthesized carbamates exhibited notable activity. Compound 24,
      methyl 6-[(5-(4-bromophenacylsulfanyl)-[1,3,4]-oxadiazol-2
      yl)methoxy]benzothiazole-2-carbamate, displayed an equipotent effect to the
      reference drug oxyclozanide at a concentration of 80 MUg mL-1; compounds 9, 10
      and 23 showed high orders of anthelmintic effect. A structural computational
      study on the polar nature and hydrophilic-lipophilic properties of the
      synthesized carbamates was undertaken to discuss their structure-activity
      relationship (SAR). Besides, pharmacophore mapping was performed using eight
      active compounds as a training set. The generated pharmacophore model revealed
      five common features and was validated using fenbendazole, triclabendazole and
      triclabendazole sulfoxide.

PMID- 30108856
TI  - Assessing the performance of docking scoring function, FEP, MM-GBSA, and QM/MM
      GBSA approaches on a series of PLK1 inhibitors.
AB  - Over-expressed polo-like kinases 1, a key regulator of cell mitosis, is
      associated with carcinogenesis and poor prognosis. It is very necessary to
      develop a reliable computational affinity prediction protocol targeting PLK1. In
      this study, the performance of different docking scoring function, free energy
      perturbation, MM-GBSA and QM/MM-GBSA were evaluated. The ranking capability of
      FEP is the best with rs = 0.854. However, the rs obtained from MM-GBSA can reach
      0.767, which requires only about one-eighth of the simulation time of FEP. As for
      the sampling method, single long molecular dynamics (SLMD) surpass the multiple
      short molecular dynamics (MSMD) in ranking of the 20 congeneric compounds by
      about 0.1 in rs. In addition, ligands treated by QM can significantly improve the
      ranking performance. As for the docking scoring functions, a force field-based
      scoring function is more suitable for ranking congeneric compounds.

PMID- 30108857
TI  - Synthesis and pharmacological evaluation of multi-functional homoisoflavonoid
      derivatives as potent inhibitors of monoamine oxidase B and cholinesterase for
      the treatment of Alzheimer's disease.
AB  - A series of homoisoflavonoid derivatives was designed, synthesized and evaluated
      as potential multi-functional anti-Alzheimer's agents for their inhibitory
      activity on cholinesterase and monoamine oxidase. Among them, compound 16 showed
      moderate acetylcholinesterase (AChE) inhibitory activity (eeAChE IC50 = 0.89 +/-
      0.02 MUM; hAChE IC50 = 0.657 +/- 0.002 MUM) and significant monoamine oxidase B
      (MAO-B) inhibitory activity (hMAO-B IC50 = 0.0372 +/- 0.0002 MUM). Kinetic
      analysis of AChE, MAO-B inhibition and molecular modeling studies revealed that
      compound 16 is a dual binding site inhibitor of AChE and noncompetitive inhibitor
      of MAO-B. Furthermore, 16 could penetrate through the blood-brain barrier (BBB)
      in vitro. Most importantly, oral administration of 16 demonstrated no marked
      signs of acute toxicity and it could significantly reverse scopolamine-induced
      memory impairment in mice. These results suggested that compound 16 is a
      promising multifunctional drug candidate with potential effect for the treatment
      of Alzheimer's disease.

PMID- 30108858
TI  - Synthesis of novel inhibitors of alpha-amylase based on the thiazolidine-4-one
      skeleton containing a pyrazole moiety and their configurational studies.
AB  - Postprandial hyperglycemia can be controlled by delaying the absorption of
      glucose resulting from carbohydrate digestion. alpha-Amylase is the initiator of
      the hydrolysis of polysaccharides, and therefore developing alpha-amylase
      inhibitors can lead to development of new treatments for metabolic disorders like
      diabetes mellitus. In the present work, we set out to rationally develop alpha
      amylase inhibitors based on the thiazolidine-4-one scaffold. The structures of
      all these newly synthesized hybrids were confirmed by spectroscopic analysis (IR,
      1H-NMR, MS). The appearance of two sets of signals for some protons in 1H NMR
      revealed the existence of a mixture of 2E,5Z (37.1-42.0%) and 2Z,5Z isomers (58.4
      62.8%), which was further supported by DFT studies. All the newly synthesized
      compounds have potential inhibitory properties as revealed through in vitro alpha
      amylase inhibition activity. Compound 5a at 100 MUg mL-1 concentration showed a
      remarkable inhibition of 90.04%. In vitro alpha-amylase inhibition was further
      supported by docking studies of compound 5a against the active site of human
      pancreatic alpha-amylase (PDB ID: ; 2QV4). The docking studies revealed that the
      bonding interactions found between 5a and human pancreatic alpha-amylase are
      similar to those responsible for alpha-amylase inhibition by acarbose.

PMID- 30108859
TI  - Synthesis, alpha-glucosidase inhibition and molecular docking studies of novel
      thiazolidine-2,4-dione or rhodanine derivatives.
AB  - A series of novel thiazolidine-2,4-dione or rhodanine derivatives (5a-5k, 6a-6k)
      were synthesized and evaluated for their alpha-glucosidase inhibitory activity.
      The majority of compounds exhibited potent inhibitory activity in the range of
      5.44 +/- 0.13 to 50.45 +/- 0.39 MUM, when compared to the standard drug acarbose
      (IC50 = 817.38 +/- 6.27 MUM). Among the compounds in the series, compounds 5k,
      6a, 6b, 6e, 6h and 6k showed potent inhibitory potential with IC50 values of
      20.95 +/- 0.21, 16.11 +/- 0.19, 7.72 +/- 0.16, 7.91 +/- 0.17, 6.59 +/- 0.15 and
      5.44 +/- 0.13 MUM, respectively. Compound 6k (IC50 = 5.44 +/- 0.13 MUM),
      containing chloro and rhodanine groups at the 2- and 4-positions of the phenyl
      ring respectively, was found to be the most active compound that inhibits alpha
      glucosidase activity. Furthermore, molecular docking studies were performed to
      understand the binding interactions between the molecule and enzyme.

PMID- 30108860
TI  - Rational design and optimization of selenophenes with basic side chains as novel
      potent selective estrogen receptor modulators (SERMs) for breast cancer therapy.
AB  - To increase the diversity of estrogen receptor (ER) ligands having novel
      structures and activities, series of selenophene derivatives with a basic side
      chain (BSC) were synthesized and their biological activity as subtype-selective
      antagonists for the ER was explored. Compared with the selenophenes without a
      BSC, most compounds showed an increase in binding affinity, and several compounds
      displayed enhanced antagonist potency and antiproliferative activity. Especially,
      compound 16c exhibited excellent transcriptional activity for ERalpha (IC50 = 13
      nM) which made this compound the most potent antagonist for ERalpha of the whole
      series and is 66-fold better than the best selenophene compound without a BSC.
      Moreover, several compounds showed values of IC50 better than that of 4
      hydroxytamoxifen in breast cancer MCF-7 cells. The modeling study indicated that
      the basic side chain might contribute to their increased antagonist potency and
      antiproliferative activity. These new ligands have the potential to be further
      developed as novel agents to improve therapeutics that target the estrogen
      receptor.

PMID- 30108861
TI  - 18alpha-Glycyrrhetinic acid monoglucuronide as an anti-inflammatory agent through
      suppression of the NF-kappaB and MAPK signaling pathway.
AB  - Based on the SAR analysis of glycyrrhizin, 18alpha-glycyrrhetinic acid
      monoglucuronide (18alpha-GAMG) with strong inhibition against LPS-induced NO and
      IL-6 production in RAW264.7 cells was discovered. Western blotting and
      immunofluorescence results showed that 18alpha-GAMG reduced the expression of
      iNOS, COX-2, and MAPKs, as well as activation of NF-kappaB in the LPS-stimulated
      RAW264.7 cells. Further in vivo results showed that 18alpha-GAMG could
      significantly improve the pathological changes of CCl4-induced hepatic fibrosis.

PMID- 30108863
TI  - Synergic modulation of the inflammatory state of macrophages utilizing anti
      oxidant and phosphatidylserine-containing polymer-lipid hybrid nanoparticles.
AB  - Inflammatory activation of macrophages is a key factor in chronic inflammatory
      diseases such as ulcerative colitis. The excessive production of reactive oxygen
      species (ROS)/reactive nitrogen species (RNS) by macrophages causes oxidative
      stress during the inflammatory response and exaggerates inflammatory lesions in
      ulcerative colitis. Inhibition of the inflammatory activation of macrophages is a
      promising treatment for chronic inflammatory diseases. Here, we prepared self
      filling polymer-lipid hybrid nanoparticles (PST-PLNPs) consisting of poly dl
      lactic acid as a hydrophobic biodegradable polymer core encapsulating alpha
      tocopherol (T) and phosphatidylserine (PS) both on the surface and interior of
      the particle. We confirmed the anti-inflammatory response of these hybrid
      nanoparticles in activated murine macrophages. PS has anti-inflammatory effects
      on macrophages by modulating the macrophage phenotype, while alpha-tocopherol is
      an antioxidant that neutralizes ROS. We found that PS-containing (PS-PLNPs) and
      PS plus alpha-tocopherol-containing (PST-PLNPs) polymer-lipid hybrid
      nanoparticles significantly increased the viability of lipopolysaccharide (LPS)
      treated macrophages compared with phosphatidylcholine-containing PLNPs. PST-PLNPs
      had a better effect than PS-PLNPs, which was attributed to the synergy between PS
      and alpha-tocopherol. This synergic action of PST-PLNPs reduced NO and pro
      inflammatory cytokine (IL-6) production and increased anti-inflammatory cytokine
      (TGF-beta1) production when incubated with activated macrophages. Thus, these
      self-filling biodegradable polymer-lipid hybrid nanoparticles (PST-PLNPs)
      containing anti-oxidant and anti-inflammatory molecules might be potential
      alternative drug carriers to liposomes and polymeric nanoparticles for the
      treatment of chronic inflammatory diseases such as ulcerative colitis.

PMID- 30108862
TI  - Synthesis and chemical characterization of several perfluorinated sialic acid
      glycals and evaluation of their in vitro antiviral activity against Newcastle
      disease virus.
AB  - Newcastle Disease Virus (NDV), belonging to the Paramyxoviridae family, causes a
      serious infectious disease in birds, resulting in severe losses in the poultry
      industry every year. Haemagglutinin neuraminidase glycoprotein (HN) has been
      recognized as a key protein in the viral infection mechanism, and its inhibition
      represents an attractive target for the development of new drugs based on sialic
      acid glycals, with the 2-deoxy-2,3-didehydro-d-N-acetylneuraminic acid
      (Neu5Ac2en) as their backbone. Herein we report the synthesis of several
      Neu5Ac2en glycals and of their perfluorinated C-5 modified derivatives, including
      their respective stereoisomers at C-4, together with evaluation of their in vitro
      antiviral activity. While all synthesized compounds were found to be active HN
      inhibitors in the micromolar range, we found that their potency was influenced by
      the chain-length of the C-5 perfluorinated acetamido functionality. Thus, the
      binding modes of the inhibitors were also investigated by performing a docking
      study. Moreover, the perfluorinated glycals were found to be more active than the
      corresponding normal C-5 acylic derivatives. Finally, cell-cell fusion assays on
      NDV infected cells revealed that the addition of a newly synthesized C-4alpha
      heptafluorobutyryl derivative almost completely inhibited NDV-induced syncytium
      formation.

PMID- 30108865
TI  - Synthesis of novel pentacyclic triterpene-Neu5Ac2en derivatives and investigation
      of their in vitro anti-influenza entry activity.
AB  - Sialic acid derivatives, analogs, and their conjugates are important
      pharmacophores. Modification of the C-4 hydroxyl group of sialic acid can lead to
      derivatives, such as zanamivir, with potent anti-influenza activities. Herein, we
      described the synthesis of C-4-modified sialic acid derivatives via conjugation
      with naturally derived pentacyclic triterpenes, which are active ingredients of
      traditional Chinese medicine, and the evaluation of their in vitro anti-influenza
      virus activity in MDCK cells. Interestingly, a set of configurational isomers was
      obtained during the de-O-acetylation reaction of two pentacyclic triterpene
      sialic acid conjugates under Zemplen conditions, and a mechanism was proposed.
      Owing to the attachment of the Neu5Ac2en moiety, all synthesized conjugates
      displayed lower hydrophobicity than their parent compounds. In comparison with
      ursane- and lupane-type triterpenes, oleanane-type triterpene-functionalized
      Neu5Ac2en conjugates were most promising. The insertion of a (1,2,3-triazol-4-yl)
      methyl between the amide bond and Neu5Ac2en caused a substantial decrease in
      activity. Compound 15a exhibited the highest inhibitory activity (IC50 = 8.3 MUM)
      and selectivity index (SI = 22.7). Further studies involving hemagglutination
      inhibition and neuraminidase inhibition suggested that compound 15a inhibited
      virus-induced hemagglutination with no effect on the enzymatic activity of
      neuraminidase, indicating that the antiviral activity appeared to be mediated via
      interaction with hemagglutinin at the initial stage of viral infection.

PMID- 30108864
TI  - Characterization and lymphocyte proliferation activity of an oligosaccharide
      degraded from Astragalus polysaccharide.
AB  - An Astragalus oligosaccharide (AOS) degraded from Astragalus polysaccharide (APS)
      and purified by membrane dialysis and silicon gel chromatography is studied in
      this paper. The structural features of AOS were investigated by a combination of
      chemical and instrumental analysis, such as monosaccharide analysis, periodate
      oxidation-Smith degradation, methylation analysis, electrospray ionization mass
      spectrometry (ESI-MS), Fourier transform infrared (FT-IR) spectrometry and
      nuclear magnetic resonance (NMR). The results indicated that AOS is an
      octasaccharide that consists of (3->)-linked-Rha, (1->3)-linked-Rha, (1->3,4)
      linked-Araf, (1->3)-linked-Gal, terminal-linked-Gal and terminal-linked-Glc. The
      effects of AOS on cyclophosphamide-induced immunosuppression were determined by
      various studies, such as the proliferation of nucleated marrow, red blood cell
      (RBC) and white blood cell (WBC) populations, growth of the spleen and thymus,
      and increases in hemoglobin (HGB) concentration and granulocyte-macrophage colony
      stimulating factor (GM-CSF) level. The results indicated that AOS can restore
      cyclophosphamide-induced immunosuppression by stimulating the secretion of GM
      CSF, which promoted the differentiation of progenitor cells after proliferation.

PMID- 30108866
TI  - Deciphering the origins of molecular toxicity of combretastatin A4 and its
      glycoconjugates: interactions with major drug transporters and their safety
      profiles in vitro and in vivo.
AB  - Cellular uptake and transport mechanisms directly correlate with the drug-like
      profiles of lead compounds. To decipher the molecular origin of the toxicity of
      combretastatin A4 (CA4), an important microtubule targeting agent, we
      investigated the interactions between CA4 and six key drug transporters, namely
      hOAT1, hOAT3, hOCT1, hOCT2, hOATP1B3, and hOATP2B1. Three combretastatin-based
      glycoconjugates, namely Glu-CA4, Man-CA4, and Gal-CA4 with glucose, mannose, and
      galactose respectively, were synthesized and their in vitro and in vivo
      biological characteristics were evaluated. CA4 exhibited significant inhibition
      against hOAT3 and hOATP2B1, moderate inhibition of hOAT1 and hOCT2, and weak
      inhibitory effects on hOCT1 and hOATP1B3. Compared to CA4, the inhibitory
      activities of Glu-CA4 on the six transporters were minimal. The glycoconjugates
      were found to have a superior safety profile with their maximum tolerated dose
      (MTD) values exhibiting a 16-34-fold increase compared to CA4. Given the
      drawbacks of CA4, the enhanced solubility and safety profiles of CA4
      glycoconjugates augur well for further investigation into these intriguing
      candidates' in vivo efficacy.

PMID- 30108867
TI  - Structure-metabolism-relationships in the microsomal clearance of piperazin-1
      ylpyridazines.
AB  - In this study, we provide insight into the metabolic profile of a series of
      piperazin-1-ylpyridazines suffering from rapid in vitro intrinsic clearance in a
      metabolic stability assay using liver microsomes (e.g. compound 1 MLM/HLM t1/2 =
      2/3 min). Aided by empirical metabolite identification and computational
      predictive models, we designed the structural modifications required to improve
      in vitro intrinsic clearance by more than 50-fold (e.g. compound 29 MLM/HLM t1/2
      = 113/105 min).

PMID- 30108869
TI  - Developments of bioorthogonal handle-containing photo-crosslinkers for
      photoaffinity labeling.
AB  - Photoaffinity labeling (PAL) has been widely applied in various research areas
      such as medicinal chemistry, chemical biology and structural biology, owing to
      its capability of investigating non-covalent ligand-protein interactions under
      native environments and elucidating protein structures, functions etc. One
      important application of this technique is to use affinity-based proteome
      profiling (AfBP) coupled with bioimaging for profiling drug-target interactions
      in situ. In order to accurately report drug-target interactions via these
      approaches, several considerations as follows need to be made: (1) maximally
      retaining bioactivities of photoprobes upon functionalization with a
      photoreactive group and a reporter tag from a parental compound; (2) performing
      proteome profiling and imaging in situ simultaneously, to monitor drug-target
      interactions in different manners; and (3) developing excellent photo
      crosslinkers capable of photo-crosslinking and fluorescence turn-on at the same
      time. With these considerations in mind, we have developed three versions of
      "minimalist" bioorthogonal handle-containing photo-crosslinkers (L3-L6) during
      the years and successfully applied them in all kinds of small bioactive molecules
      for protein labeling and cellular imaging studies. In this mini-review, the
      features and functions of these linkers are specifically highlighted and
      summarized.

PMID- 30108868
TI  - Identification of potent cholecystokinin-B receptor antagonists: synthesis,
      molecular modeling and anti-cancer activity against pancreatic cancer cells.
AB  - Advanced malignant stages of pancreatic cancer have poor prognosis and very few
      treatment strategies are available. Pancreatic cancer is known to possess unique
      growth-related receptors that when activated, stimulate tumour proliferation.
      Gastrin and its related peptide cholecystokinin (CCK) are also significantly
      involved in the growth of this cancer type as well as other malignancies through
      activation of the cholecystokinin-B receptor (CCK-BR). New treatment strategies
      with CCK-BR antagonists are being suggested that suppress the growth promoting
      effects of gastrin. In this paper, we report the development of two series of
      quinazolinone derivatives incorporating hydrazinecarbothioamide (compounds 3a-g)
      and the hydrazino group (compounds 4a-e) as linkers for developing CCK-BR
      antagonists. The affinities of the compounds were determined using docking into
      the CCK-BR homology modeled structure. The compounds were tested for in vitro CCK
      BR binding and gastric acid secretion in an isolated lumen-perfused mouse stomach
      assay. The compounds exhibited CCK-BR binding activity (IC50) in the range of 0.2
      975 nM and showed good gastric acid secretion inhibitory activity. Molecular
      modeling of the compounds was done and pharmacophore mapping results showed good
      prediction of in vitro activity which correlated well with the experimental
      antagonistic activity. The compounds were further tested for their cytotoxicity
      on CCK-BR expressing pancreatic cancer cells. The results of the study provided
      two potent CCK-BR antagonists which also possess good to moderate growth
      inhibitory activities against pancreatic cancer cells.

PMID- 30108871
TI  - Approaches to selective fibroblast growth factor receptor 4 inhibition through
      targeting the ATP-pocket middle-hinge region.
AB  - A diverse range of selective FGFR4 inhibitor hit series were identified using
      unbiased screening approaches and by the modification of known kinase inhibitor
      scaffolds. In each case the origin of the selectivity was consistent with an
      interaction with a poorly conserved cysteine residue within the middle-hinge
      region of the kinase domain of FGFR4, at position 552. Targeting this region
      identified a non-covalent diaminopyrimidine series differentiating by size, an
      irreversible-covalent inhibitor in which Cys552 undergoes an SNAr reaction with a
      2-chloropyridine, and a reversible-covalent inhibitor series in which Cys552
      forms a hemithioacetal adduct with a 2-formyl naphthalene. In addition, the
      introduction of an acrylamide into a known FGFR scaffold identified a pan-FGFR
      inhibitor which reacted with both Cys552 and a second poorly conserved cysteine
      on the P-loop of FGFR4 at position 477 which is present in all four FGFR family
      members.

PMID- 30108872
TI  - On-DNA Pd and Cu promoted C-N cross-coupling reactions.
AB  - Encoded library technology (ELT) is a novel hit identification platform
      synergistic with HTS, fragment hit ID and focused screening. It provides both an
      ultra high-throughput and a cost-efficient tool for the discovery of small
      molecules that bind to protein targets of pharmaceutical interest. The success of
      ELT relies heavily on the chemical diversity accessed through DNA-encoded library
      (DEL) synthesis. We developed unprecedented Pd and Cu(i) promoted C-N cross
      coupling reactions between a DNA-conjugated aryl iodide and primary amines. These
      reported reactions have strong potential for application in DNA-encoded library
      (DEL) synthesis.

PMID- 30108870
TI  - Recent advances in combretastatin based derivatives and prodrugs as antimitotic
      agents.
AB  - The dynamic and crucial role of tubulin in different cellular functions rendered
      it a promising target in anticancer drug development. Combretastatin A-4 (CA-4),
      an inhibitor of tubulin polymerization isolated from natural sources, is a lead
      molecule with significant cytotoxicity against tumour cells. Owing to its non
      polar nature it exhibits low solubility in natural biological fluids, thereby
      prompting the development of new CA-4 based derivatives. The modification of this
      lead molecule was mostly carried out by keeping the crucial cis-orientation of
      the double bond intact, along with a trimethoxyphenyl aromatic ring, by employing
      different approaches. The issue of solubility was also addressed by the
      development of water soluble prodrugs of CA-4. The present review highlights the
      investigations into the parallel development of both new CA-4 based derivatives
      and prodrugs in the past few years.

PMID- 30108874
TI  - Discovery of potential antifungal triazoles: design, synthesis, biological
      evaluation, and preliminary antifungal mechanism exploration.
AB  - A series of triazoles as miconazole analogues was designed, synthesized and
      characterized by IR, NMR, MS and HRMS. All the newly prepared compounds were
      screened for their antifungal activities against five kinds of fungi. The
      bioactive assay showed that most of the synthesized compounds exhibited good or
      even stronger antifungal activities in comparison with the reference drugs
      miconazole and fluconazole. In particular, the 3,4-dichlorobenzyl derivative 5b
      showed a comparable or superior activity against all the tested fungal strains to
      standard drugs, and formed a supramolecular complex with CYP51 via the hydrogen
      bond between the 4-nitrogen of the triazole nucleus and the histidine residue.
      Preliminary experiments revealed that both of the active molecules 5b and 9c
      could intercalate into calf thymus DNAs, which might block DNA replication to
      exhibit their powerful antifungal abilities. Further studies indicated that
      compound 5b might be stored and transported by human serum albumin through
      hydrophobic interactions, specific electrostatic interactions and hydrogen bonds.
      These results strongly suggested that compound 5b could serve as a promising
      antifungal candidate.

PMID- 30108873
TI  - Synthesis, molecular modeling and biological evaluation of aza-flavanones as
      alpha-glucosidase inhibitors.
AB  - An efficient acid catalyzed methodology has been employed to synthesize a variety
      of aza-flavanones and their alpha-glucosidase inhibitory activity is evaluated
      using acarbose, miglitol and voglibose as reference standards. Molecular modeling
      studies were performed for all compounds to identify the important binding modes
      responsible for the inhibition activity of alpha-glucosidase which helped find
      key interactions between the enzyme and the active compounds. Among all the
      compounds 5g, 5r and 5w have shown high alpha-glucosidase inhibition activity
      compared to standard reference drugs and have been identified as promising
      potential antidiabetic agents. This study is the first biological evaluation of
      aza-flavanones as alpha-glucosidase inhibitors.

PMID- 30108876
TI  - Design, synthesis, and biological evaluation of new thiazolo[5,4-d]pyrimidine
      derivatives as potent antiproliferative agents.
AB  - A series of thiazolo[5,4-d]pyrimidine derivatives were synthesized and evaluated
      for their antiproliferative activities against several human cancer cell lines.
      Structure-activity relationship studies were carried out, showing that most of
      the target compounds had good inhibition against the tested cell lines. Among
      them, compound 7i exhibited potent inhibition against human gastric cancer cells
      MGC-803 and HGC-27 with IC50 values of 4.64 and 5.07 MUM, respectively and around
      12-fold selectivity between MGC-803 and GES-1, indicating a relatively low
      toxicity to normal cells. The potency and low toxicity of compound 7i make the
      thiazolo[5,4-d]pyrimidine an attractive scaffold for designing new derivatives
      selectively targeting MGC-803 cells.

PMID- 30108877
TI  - Environment-sensitive turn-on fluorescent probes for p53-MDM2 protein-protein
      interaction.
AB  - A series of probes with a turn-on switch for the p53-MDM2 protein-protein
      interaction were developed. After careful evaluation, these small molecule
      fluorescent probes exhibited high practical activity and selectivity in vitro and
      in cellulo. In particular probe 10, which had a Ki value of 0.03 MUM, displayed
      much better binding affinity compared to the positive control Nutlin-3, which had
      a Ki value of 0.23 MUM. These no-wash environment-sensitive turn-on fluorescent
      probes have been successfully applied to imaging p53-MDM2 interaction in the
      human lung cancer cell line A549 (wild-type p53) at the micromolar level.
      Therefore, these fluorescent probes are expected to be used in drug screening and
      cell staining in p53-MDM2 fields, as well as in pathological and physiological
      studies of the p53-MDM2 interaction.

PMID- 30108875
TI  - Synthesis and evaluation of oxindoles as promising inhibitors of the
      immunosuppressive enzyme indoleamine 2,3-dioxygenase 1.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as an important therapeutic
      target for the treatment of cancer, chronic infections and other diseases that
      are associated with immune suppression. Recent developments in understanding the
      catalytic mechanism of the IDO1 enzyme revealed that conversion of l-tryptophan
      (l-Trp) to N-formylkynurenine proceeded through an epoxide intermediate state.
      Accordingly, we synthesized a series of 3-substituted oxindoles from l-Trp,
      tryptamine and isatin. Compounds with C3-substituted oxindole moieties showed
      moderate inhibitory activity against the purified human IDO1 enzyme. Their
      optimization led to the identification of potent compounds, 6, 22, 23 and 25
      (IC50 = 0.19 to 0.62 MUM), which are competitive inhibitors of IDO1 with respect
      to l-Trp. These potent compounds also showed IDO1 inhibition potencies in the low
      micromolar range (IC50 = 0.33-0.49 MUM) in MDA-MB-231 cells. The cytotoxicity of
      these potent compounds was trivial in different model cancer (MDA-MB-231, A549
      and HeLa) cells and macrophage (J774A.1) cells. Stronger selectivity for the IDO1
      enzyme (124 to 210-fold) over the tryptophan 2,3-dioxygenase (TDO) enzyme was
      also observed for these compounds. These results suggest that the oxindole moiety
      of the compounds could mimic the epoxide intermediate state of l-Trp. Therefore,
      the structural simplicity and low-micromolar inhibition potencies of these 3
      substituted oxindoles make them quite attractive for further investigation of
      IDO1 function and immunotherapeutic applications.

PMID- 30108878
TI  - Extraction of antioxidant and antiproliferative ingredients from fruits of Rubus
      chingii Hu by active tracking guidance.
AB  - Rubus chingii Hu, namely "Fu-pen-zi" in Chinese, has been used as a functional
      food in China for a long time. This study aims to identify its bioactive
      constituents with antioxidant and anti-tumor properties. R. chingii was extracted
      with 95% ethanol and then partitioned into four fractions: petroleum ether
      fraction, ethyl acetate fraction, n-butanol fraction, and water fraction. Results
      showed that the ethyl acetate fraction had the strongest antioxidant activity and
      cytotoxicity against human cancer cell lines (HepG-2, Bel-7402, A549 and MCF-7).
      Therefore, four compounds were isolated from the ethyl acetate fraction, and they
      were identified as ent-16alpha,17-dihydroxy-kauran-19-oic acid, tormentic acid,
      oleanolic acid and beta-daucosterol, the first two of which were isolated and
      identified from R. chingii for the first time. In particular, tormentic acid
      exhibited excellent cytotoxicity activities against human tumor cell lines. The
      results obtained in this work might contribute to the understanding of biological
      activities of R. chingii and further investigation on its potential application
      is valued for food and drugs.

PMID- 30108879
TI  - Biscarbene gold(i) complexes: structure-activity-relationships regarding
      antibacterial effects, cytotoxicity, TrxR inhibition and cellular
      bioavailability.
AB  - A series of gold(i) complexes with two N-heterocyclic carbene ligands (biscarbene
      gold complexes) were prepared and evaluated for their effects against cancer
      cells and pathogenic bacteria. Proliferation inhibition was observed in cancer
      cells and in Gram-positive bacteria, whereas Gram-negative bacteria were less
      sensitive towards the compounds. The protein binding and cellular uptake were
      quantified and the combined results indicated a strong correlation between
      cellular bioavailability and antiproliferative effects. The biscarbene gold
      complexes inhibited bacterial and mammalian TrxRs with low to moderate potency.
      However, based on the obtained structure-activity-relationships and the high
      cellular accumulation levels, TrxR inhibition can be considered as a relevant
      contributor to the cellular pharmacology of biscarbene gold(i) complexes.

PMID- 30108880
TI  - Development of selective agents targeting serotonin 5HT1A receptors with
      subnanomolar activities based on a coumarin core.
AB  - A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from
      the corresponding bromoalkyl derivatives have been designed and synthesized by us
      using a microwave-assisted protocol. Radioligand binding assays of this series of
      compounds as well as a previously synthesized series of 17 structurally-similar
      compounds showed that six systems have very high affinities to the 5-HT1A
      receptor (0.3-1.0 nM) and good selectivity against the 5-HT2A receptor. Molecular
      docking, structural studies and structure-activity relationship studies were used
      to gain more insight into the atomistic details of ligand binding and rationalize
      the obtained results.

PMID- 30108881
TI  - Bioisosteric replacement of central 1,2,4-oxadiazole ring of high affinity CB2
      ligands by regioisomeric 1,3,4-oxadiazole ring.
AB  - It has been reported that bioisosteric replacement of an 1,2,4-oxadiazole ring by
      an 1,3,4-oxadiazole ring leads to higher polarity, reduced metabolic degradation
      by human liver microsomes and reduced interaction with hERG channels. In a seven
      to eight step synthesis 1,3,4-oxadiazles 9a-c were synthesized as bioisosteric
      analogs of high-affinity but rather lipophilic CB2 ligands 1a-c containing an
      1,2,4-oxadiazole ring. The 1,3,4-oxadiazole derivatives 9a and 9b show 10- and 50
      fold reduced CB2 affinity compared to the 1,2,4-oxadiazole derivatives 1a and 1b,
      respectively. However, the 1,3,4-oxadiazole 9a has high CB2 affinity (Ki = 25 nM)
      and high selectivity over the CB1 receptor.

PMID- 30108884
TI  - There's room for a little randomness in drug development.
AB  - Setting free the dark horses sometimes beats the most rational planning.

PMID- 30108882
TI  - Synthesis and molecular docking studies of xanthone attached amino acids as
      potential antimicrobial and anti-inflammatory agents.
AB  - A series of novel xanthone conjugated amino acids were synthesised and
      characterised by analytical and spectroscopic methods. All the synthesized
      analogues (2-23) were screened for their in vitro antimicrobial and anti
      inflammatory activities. Compounds 7, 8, 9, 12, 18, 19, 20, 21 and 23 showed
      excellent antimicrobial activities compared to antibacterial and antifungal
      reference drugs gentamicin and bavistin, respectively. Compounds 7-12 and 18-23
      showed good anti-inflammatory activity compared to a standard drug, indomethacin.
      The preliminary structure-activity relationship revealed that tryptophan,
      tyrosine, phenylalanine, proline and cysteine conjugated compounds showed
      excellent antimicrobial and anti-inflammatory activities. This may be explained
      by the contribution of aromaticity and hydrophobicity of amino acids. Molecular
      docking studies were performed for all the synthesised compounds, among which
      compounds 20, 21 and 23 showed the highest docking scores for antimicrobial
      activity while compounds 9, 20 and 22 showed the highest docking scores for anti
      inflammatory activity. Different amino acids conjugated xanthone derivatives were
      synthesized and evaluated for their in vitro biological activities. The
      conjugation was found to play a major role in improving the biological activities
      of those compounds.

PMID- 30108883
TI  - Discovery of human lactate dehydrogenase A (LDHA) inhibitors as anticancer agents
      to inhibit the proliferation of MG-63 osteosarcoma cells.
AB  - Human lactate dehydrogenase A (LDHA) has been identified as a potential
      therapeutic target in the area of cancer metabolism. Herein, we report the
      discovery of novel LDHA inhibitors through docking-based virtual screening and
      biological assays. The primary enzymatic assay suggested that compound 11
      targeted LDHA with an IC50 value of 0.33 MUM. The in vitro cytotoxic assay
      demonstrated that compound 11 reduced the growth of MG-63 cancer cells with an
      EC50 value of 3.35 MUM. Finally, we found that compound 11 induced the apoptosis
      of MG-63 cancer cells in a dose dependent manner, upregulated the oxygen
      consumption rate (OCR), and decreased the lactate formation and extracellular
      acidification rate (ECAR) in MG-63 cancer cells. Collectively, our data suggested
      that compound 11 could be a promising lead for the development of potent LDHA
      inhibitors.

PMID- 30108885
TI  - What is medicinal chemistry? - Demystifying a rapidly evolving discipline!
AB  - Medicinal chemistry is a scientific discipline that has progressed rapidly over
      the last few decades. Facilitated by the technological advancement, the early
      understanding of medicinal chemistry as "synthesizing bioactive molecules" has
      become the connecting bridge of a variety of related scientific disciplines. This
      opinion article will guide you through a brief evolution of this discipline and
      discuss what medicinal chemistry has evolved to be in this era.

PMID- 30108887
TI  - Polyhydroxyalkanoates as biomaterials.
AB  - Polyhydroxyalkanoates (PHAs) are biopolymers synthesized by bacteria under
      unbalanced growth conditions. These biopolymers are considered as potential
      biomaterials for future applications because they are biocompatible,
      biodegradable, and easy to produce and functionalize with strong mechanical
      strength. Currently, PHAs are being extensively innovated for biomedical
      applications due to their prerequisite properties. The wide range of biomedical
      applications includes drug delivery systems, implants, tissue engineering,
      scaffolds, artificial organ constructs, etc. In this article we review the
      utility of PHAs in various forms (bulk/nano) for biomedical applications so as to
      bring about the future vision for PHAs as biomaterials for the advancement of
      research and technology.

PMID- 30108888
TI  - MAO inhibitory activity of bromo-2-phenylbenzofurans: synthesis, in vitro study,
      and docking calculations.
AB  - Monoamine oxidase (MAO) is an enzyme responsible for metabolism of monoamine
      neurotransmitters which play an important role in brain development and function.
      This enzyme exists in two isoforms, and it has been demonstrated that MAO-B
      activity, but not MAO-A activity, increases with aging. MAO inhibitors show
      clinical value because besides the monoamine level regulation they reduce the
      formation of by-products of the MAO catalytic cycle, which are toxic to the
      brain. A series of 2-phenylbenzofuran derivatives was designed, synthesized and
      evaluated against hMAO-A and hMAO-B enzymes. A bromine substituent was introduced
      in the 2-phenyl ring, whereas position 5 or 7 of the benzofuran moiety was
      substituted with a methyl group. Most of the tested compounds inhibited
      preferentially MAO-B in a reversible manner, with IC50 values in the low micro or
      nanomolar range. The 2-(2'-bromophenyl)-5-methylbenzofuran (5) was the most
      active compound identified (IC50 = 0.20 MUM). In addition, none of the studied
      compounds showed cytotoxic activity against the human neuroblastoma cell line SH
      SY5Y. Molecular docking simulations were used to explain the observed hMAO-B
      structure-activity relationship for this type of compounds.

PMID- 30108889
TI  - Synthesis of surface capped mesoporous silica nanoparticles for pH-stimuli
      responsive drug delivery applications.
AB  - Mesoporous silica-based drug delivery carriers mostly require appropriate surface
      modifications to improve their drug delivery efficiency and to reduce their
      adverse side effects. In the present work, we have synthesised mesoporous silica
      nanoparticles and their surface was covered by using capping units such as
      tetrathio-maleimide (TTM) via a "host-guest" complexation mechanism for pH
      responsive drug delivery applications. The surface-functionalised melamine (Mela)
      groups on the outer surface of the mesoporous silica nanoparticles act as "hosts"
      and the surface capped TTM units act as "guests" during the surface capping of
      the mesoporous silica nanoparticles via the "host-guest" complexation approach.
      After the encapsulation of cargoes into the mesopore channels, the melamine
      functional groups were covalently immobilised onto the outer surface of the cargo
      loaded MSNs and then the TTM units were introduced onto the outer surface of the
      silica nanoparticles as "gatekeepers" to obtain surface capped mesoporous silica
      (MSN@Mela@TTM/RhB) NPs to protect the loaded cargo molecules inside the mesopore
      channels and to prevent their premature leakage. The surface-capped TTM units
      controlled the drug release behavior with respect to the pH of the release
      medium. In this study, we used rhodamine B (RhB) as a model cargo to study the
      loading and pH-responsive release behavior of the MSN@Mela@TTM NPs. The
      encapsulated RhB molecules were retained inside the mesopore channels at
      physiological pH (pH 7.4) conditions while an enhanced release occurred at acidic
      pH (pH 5.0 and 4.0) conditions, respectively. Furthermore, the in vitro
      biocompatibility and the intracellular uptake efficiency of the synthesised
      MSNs@Mela@TTM NPs were examined by using the MDA-MB-231 cell line. The
      experimental results suggest that the MSNs@Mela@TTM nanoparticles are
      biocompatible and could be utilised for pH-stimuli responsive drug delivery
      applications.

PMID- 30108886
TI  - Imidazoles as potential anticancer agents.
AB  - Cancer is a black spot on the face of humanity in this era of science and
      technology. Presently, several classes of anticancer drugs are available in the
      market, but issues such as toxicity, low efficacy and solubility have decreased
      the overall therapeutic indices. Thus, the search for new promising anticancer
      agents continues, and the battle against cancer is far from over. Imidazole is an
      aromatic diazole and alkaloid with anticancer properties. There is considerable
      interest among scientists in developing imidazoles as safe alternatives to
      anticancer chemotherapy. The present article describes the structural, chemical,
      and biological features of imidazoles. Several classes of imidazoles as
      anticancer agents based on their mode of action have been critically discussed. A
      careful observation has been made into pharmacologically active imidazoles with
      better or equal therapeutic effects compared to well-known imidazole-based
      anticancer drugs, which are available on the market. A brief discussion of the
      toxicities of imidazoles has been made. Finally, the current challenges and
      future perspectives of imidazole based anticancer drug development are conferred.

PMID- 30108890
TI  - Structure-optimized dihydropyranoindole derivative GIBH-LRA002 potentially
      reactivated viral latency in primary CD4+ T lymphocytes of chronic HIV-1
      patients.
AB  - Based on structure modification and a high-throughput Jurkat-Lat cell screening
      model, we found that GIBH-LRA002, ethyl-2-amino-3-cyano-9-methyl-4
      (trifluoromethyl)-4,9-dihydropyrano[2,3-b]indole-4-carboxylate, effectively
      reactivated the latent proviruses in a Jurkat-Lat cell line and primary CD4+ T
      cells from both chronic SIV-infected rhesus macaques and HIV-1 patients but
      without inducing systemic activation, making this compound attractive for
      potentially treating HIV-1 infection.

PMID- 30108891
TI  - Synthesis and biological evaluation of chalcone-linked pyrazolo[1,5-a]pyrimidines
      as potential anticancer agents.
AB  - A series of pyrazolo[1,5-a]pyrimidines substituted at C5 with 1-phenylprop-2-en-1
      one (6a-q) and 3-phenylprop-2-en-1-one (7a-k) was synthesized and evaluated for
      antiproliferative activity. Among them, 6h was found to be the most active
      compound against the MDA-MB-231 cell line with an IC50 of 2.6 MUM . The
      antiproliferative activity of this series of compounds ranged from 2.6 to 34.9
      MUM against A549 (lung cancer), MDA-MB-231 (breast cancer) and DU-145 (prostate
      cancer) cell lines. FACS analysis revealed that these hybrids arrest the cell
      cycle at the subG1 phase. Western blot analysis and an immunofluorescence assay
      showed the inhibition of the EGFR and STAT3 axis, which plays an important role
      in cell survival and apoptosis. Western blot and RT-PCR analyses that displayed
      an increase in apoptotic proteins such as p53, p21 and Bax and a decrease in the
      anti-apoptotic proteins Bcl-2 and procaspase-9 confirmed the ability of these
      hybrids to trigger cell death by apoptosis. Molecular docking studies described
      the binding of these hybrids to the ATP binding site of EGFR.

PMID- 30108892
TI  - Click chemistry-assisted synthesis of triazolo linked podophyllotoxin conjugates
      as tubulin polymerization inhibitors.
AB  - A series of new triazolo linked 4beta-amidopodophyllotoxin conjugates (9a-l) were
      synthesized using click chemistry and evaluated for their antitumor activity
      against four human cancer cell lines. Among them, two compounds (9c and 9j)
      showed significant anticancer activity with IC50 values of 0.9 and 0.07 MUM,
      respectively. Biological studies are conducted into the cell-cycle distribution
      of these conjugates inducing G2/M-phase arrest, apart from an increase in the
      levels of caspase-3 proteins, followed by apoptotic cell death. A tubulin
      polymerization assay analysis showed that these compounds effectively inhibit
      microtubule assembly in HeLa cells and, moreover, Hoechst 33258 and
      Immunohistochemistry staining suggest that these compounds induce cell death by
      apoptosis. The docking studies showed that compounds 9c and 9j interact and bind
      efficiently with the tubulin protein at the colchicine site.

PMID- 30108893
TI  - An insight into tetrahydro-beta-carboline-tetrazole hybrids: synthesis and
      bioevaluation as potent antileishmanial agents.
AB  - A series of 2,3,4,9-tetrahydro-beta-carboline tetrazole derivatives (14a-u) have
      been synthesized utilizing the Ugi multicomponent reaction and were identified as
      potential antileishmanial chemotypes. Most of the screened derivatives exhibited
      significant in vitro activity against the promastigote (IC50 from 0.59 +/- 0.35
      to 31 +/- 1.27 MUM) and intracellular amastigote forms (IC50 from 1.57 +/- 0.12
      to 17.6 +/- 0.2 MUM) of L. donovani, and their activity is comparable with
      standard drugs miltefosine and sodium stibogluconate. The most active compound
      14t was further studied in vivo against the L. donovani/golden hamster model at a
      dose of 50 mg kg-1 through the intraperitoneal route for 5 consecutive days,
      which displayed 75.04 +/- 7.28% inhibition of splenic parasite burden.
      Pharmacokinetics of compound 14t was studied in the golden Syrian hamster, and
      following a 50 mg kg-1 oral dose, the compound was detected in hamster serum for
      up to 24 h. It exhibited a large volume of distribution (651.8 L kg-1), high
      clearance (43.2 L h-1 kg-1) and long mean residence time (10 h).

PMID- 30108894
TI  - Integrating docking scores and key interaction profiles to improve the accuracy
      of molecular docking: towards novel B-RafV600E inhibitors.
AB  - A set of ninety-eight B-RafV600E inhibitors was used for the development of a
      molecular docking based QSAR model using linear and non-linear regression models.
      The integration of docking scores and key interaction profiles significantly
      improved the accuracy of the QSAR models, providing reasonable statistical
      parameters (Rtrain2 = 0.935, Rtest2 = 0.728 and QCV2 = 0.905). The established MD
      SVR (molecular docking based SMV regression) model as well as model screening of
      a natural product database was carried out and two natural products (quercetin
      and myricetin) with good prediction activities were biologically evaluated. Both
      compounds exhibited promising B-RafV600E inhibitory activities (ICQuercetin50 =
      7.59 MUM and ICMyricetin50 = 1.56 MUM), suggesting a high reliability and good
      applicability of the established MD-SVR model in the future development of B
      RafV600E inhibitors with high efficacy.

PMID- 30108895
TI  - One-pot synthesis, anti-tumor evaluation and structure-activity relationships of
      novel 25-OCH3-PPD derivatives.
AB  - Based on the fact that 25-OCH3-PPD, a natural ginsengenin isolated from the
      leaves of Panax ginseng, is a promising lead compound, novel 25-OCH3-PPD
      derivatives were synthesized to find more potent anti-tumor agents by a simple
      and facile synthetic method. These derivatives were classified into three types
      and screened for their cytotoxic activities against seven human cancer cell
      lines. Compared with 25-OCH3-PPD, compounds a5, a7, b5 and b7 exhibited higher
      anti-tumor activities on all tested cell lines with almost 5-fold to 15-fold
      increases. In particular, compound a7 showed the greatest cytotoxic activity
      against alpha-2 cells (IC50 = 2.4 +/- 0.4 MUM). The preliminary study on the
      mechanisms indicated that compound a7 could induce alpha-2 cell apoptosis.
      Structure-activity relationships demonstrated that the carbon-carbon double bond
      at the C-20 position could enhance the antiproliferative activity. In conclusion,
      the novel derivatives a5, a7, b5 and b7 could be further studied as potential
      candidates for the treatment of cancer. This research provides a theoretical
      reference for the exploration of new antiproliferative agents.

PMID- 30108896
TI  - 4-Hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3-carboxamide: a
      novel inhibitor of the canonical NF-kappaB cascade.
AB  - The NF-kappaB signaling pathway is a validated oncological target. Here, we
      applied scaffold hopping to IMD-0354, a presumed IKKbeta inhibitor, and
      identified 4-hydroxy-N-[3,5-bis(trifluoromethyl)phenyl]-1,2,5-thiadiazole-3
      carboxamide (4) as a nM-inhibitor of the NF-kappaB pathway. However, both 4 and
      IMD-0354, being potent inhibitors of the canonical NF-kappaB pathway, were found
      to be inactive in human IKKbeta enzyme assays.

PMID- 30108898
TI  - Rise of the biologics.
AB  - Antibodies, RNA and gene therapy don't necessarily compete with small molecule
      drugs - and they all rely on chemistry as well.

PMID- 30108897
TI  - Sugar modified pyrimido[4,5-b]indole nucleosides: synthesis and antiviral
      activity.
AB  - Three types of sugar modified pyrimido[4,5-b]indole nucleosides (2'-deoxy-2'
      fluororibo-, 2'-deoxy-2'-fluoroarabino- and arabinonucleosides) were synthesized
      by glycosylation of 4,6-dichloropyrimido[4,5-b]indole followed by modification of
      sugar moiety and introduction of substituents into position 4 by cross-coupling
      reactions or nucleophilic substitutions. Some 2'-fluororibo- and 2'
      fluoroarabinonucleosides displayed interesting anti-HCV activities (IC50 = 1.6-20
      MUM) and the latter compounds also some anti-dengue activities (IC50 = 10.8-40
      MUM).

PMID- 30108902
TI  - Studies on enantioselectivity of chiral 4-acetylamino-6-alkyloxy-2
      alkylthiopyrimidines acting as antagonists of the human A3 adenosine receptor.
AB  - Three A3 adenosine receptor (AR) antagonists (1-3) selected from 4-acylamino-6
      alkyloxy-2-alkylthiopyrimidines previously investigated by us were modified by
      inserting a methyl group on their ether or thioether side chains. These compounds
      gave us the chance to evaluate whether their higher lipophilicity, reduced
      conformational freedom and chirality might improve the potency towards the A3 AR.
      Racemic mixtures of 1-3 were resolved using chiral HPLC methods and the absolute
      configurations of the enantiomers were assigned by chiroptical spectroscopy and
      density functional theory calculations. We measured the affinity for human A1,
      A2A, A2B and A3 ARs of the racemic mixtures and the pure enantiomers of 1-3 by
      radioligand competition binding experiments. Cell-based assays of the most potent
      enantiomers confirmed their A3 AR antagonist profiles. Our research led to the
      identification of (S)-1 with high potency (0.5 nM) and selectivity as an A3 AR
      antagonist. Moreover we built a docking-model useful to design new pyrimidine
      derivatives.

PMID- 30108901
TI  - Synthesis and pharmaceutical characterization of site specific mycophenolic acid
      modified Xenopus glucagon-like peptide-1 analogs.
AB  - To develop novel long-acting antidiabetic agents, mycophenolic acid (MPA) was
      used to modify Xenopus glucagon-like peptide-1 analog (GLP-1) (1) at three Lys
      residues through a gamma-glutamyl linker. Similarly, 6-aminocaproic acid and 12
      aminolauric acid with different lengths of fatty chain were used as MPA
      derivatives which were then conjugated with 1. By using proper protection and
      deprotection strategies, the synthetic process was completed directly on the
      resin to minimize the side reactions, and nine MPA-modified 1 derivatives (2a-2i)
      were obtained. Compounds 2b and 2c, which showed high GLP-1 receptor activation
      potencies and glucose lowering activities, were selected for further C-terminal
      modification to improve their stabilities and bioactivities, giving compounds 3a
      3d. The receptor activation potencies and hypoglycemic activities of 3a-3d were
      comparable to that of liraglutide. Physicochemical and in vitro stability tests
      revealed that MPA conjugation led to enhanced albumin binding abilities as
      reflected by the improved stabilities of 3a-3d. In particular, at a dose of 25
      nmol kg-1, the in vivo antidiabetic and insulinotropic activities of 3d were
      comparable to those of semaglutide. Finally, long-term administration of 3d
      achieved beneficial effects on glucose tolerance normalization and glycated
      hemoglobin (HbA1c) lowering, and no hepatotoxicity was observed. In conclusion,
      this research demonstrated that MPA derivatization was a practical way to develop
      long-acting antidiabetic peptides.

PMID- 30108899
TI  - Synthesis and biological evaluation of rapamycin-derived, next generation small
      molecules.
AB  - Over the years, rapamycin has attracted serious attention due to its remarkable
      biological properties and as a potent inhibitor of the mammalian target of
      rapamycin (mTOR) protein through its binding with FKBP-12. Several efficient
      strategies that utilize synthetic and biosynthetic approaches have been utilized
      to develop small molecule rapamycin analogs or for synthesizing hybrid compounds
      containing a partial rapamycin structure to improve pharmacokinetic properties.
      Herein, we report selected case studies related to the synthesis of rapamycin
      derived compounds and hybrid molecules to explore their biological properties.

PMID- 30108900
TI  - In depth analysis of kinase cross screening data to identify chemical starting
      points for inhibition of the Nek family of kinases.
AB  - Potent, selective, and cell active small molecule kinase inhibitors are useful
      tools to help unravel the complexities of kinase signaling. As the biological
      functions of individual kinases become better understood, they can become targets
      of drug discovery efforts. The small molecules used to shed light on function can
      also then serve as chemical starting points in these drug discovery efforts. The
      Nek family of kinases has received very little attention, as judged by number of
      citations in PubMed, yet they appear to play many key roles and have been
      implicated in disease. Here we present our work to identify high quality chemical
      starting points that have emerged due to the increased incidence of broad kinome
      screening. We anticipate that this analysis will allow the community to progress
      towards the generation of chemical probes and eventually drugs that target
      members of the Nek family.

PMID- 30108904
TI  - Highly efficient antibody purification with controlled orientation of protein A
      on magnetic nanoparticles.
AB  - In this study, we prepared protein A grafted magnetic nanoparticles for the
      industrial large-scale purification of antibodies with enhancement of binding
      capacity and immobilization by controlled orientation with chlorophenylsilane
      (CPTMS) on the surface. For site-specific immobilization of protein A,
      genetically modified protein A with a cysteine residue was expressed in E. coli
      and purified by affinity chromatography. To improve the surface area to volume
      ratio and increase the immobilization amount of protein A, chlorophenylsilane
      functionalized magnetic nanoparticles (CPTMS@MNPs) were prepared, which are
      smaller nanoparticles with an average diameter of 20 nm compared to commercial
      magnetic microparticles (Dynabeads) with an average size of 2.8 MUm. The
      CPTMS@MNPs showed the enhancement of protein A immobilization and binding
      capacity to antibodies, being 11.5-fold and 7-fold higher than those of
      commercial Dynabeads, respectively. In addition, the CPTMS@MNPs retained about
      80% of the initial protein binding capacity until the third stage of recycling.
      Therefore, protein A grafted CPTMS@MNPs may be useful for the industrial large
      scale purification of antibodies.

PMID- 30108903
TI  - A beta-carboline derivative-based nickel(ii) complex as a potential antitumor
      agent: synthesis, characterization, and cytotoxicity.
AB  - A novel nickel(ii) complex of 6-methoxy-1-pyridine-beta-carboline (4a) was
      synthesized and characterized. The cytotoxicities of the complex towards six
      cancer cell lines, including MGC-803, Hep G2, T24, OS-RC-2, NCI-H460, and SK-OV
      3, and human normal liver cell line HL-7702 were investigated. The IC50 values
      for MGC-803, Hep G2, T24, OS-RC-2, NCI-H460 and SK-OV-3 were generally in the
      micromolar range (3.77-15.10 MUM), lower than those of ligand 4 and cisplatin.
      Furthermore, 4a (6 MUM) significantly induced cell cycle arrest at the S phase,
      and caused the down-regulation of p-AKT, cyclin E, cyclin A and CDK2 and the up
      regulation of p27. Various experiments showed that 4a induced apoptosis,
      activated caspase-3, increased the levels of reactive oxygen species (ROS) and
      enhanced the intracellular [Ca2+]c levels in MGC-803. In addition, the expression
      of intrinsic apoptotic proteins, including cytochrome c and apaf-1, increased.
      Further intrinsic apoptosis was triggered via executive molecular caspase-9 and
      caspase-3. In short, 4a exerted its cytotoxic activity primarily through inducing
      cell cycle arrest at the S phase and intrinsic apoptosis.

PMID- 30108907
TI  - Identification of non-substrate-like glycosyltransferase inhibitors from library
      screening: pitfalls & hits.
AB  - Bacterial glycosyltransferases are potential targets for the development of novel
      antibiotics and anti-virulence agents. Most existing glycosyltransferase
      inhibitors are substrate analogues with limited potential for drug development.
      The identification of alternative inhibitor chemotypes is therefore of great
      interest for medicinal chemistry, drug discovery and chemical glycobiology. We
      describe the application of a biochemical glycosyltransferase assay to screen a
      small compound library containing three distinct chemical scaffolds (nucleosides,
      steroids and 5-methyl pyrazol-3-ones) against the retaining alpha-1,4
      galactosyltransferase LgtC from Neisseria meningitidis. While no genuine LgtC
      inhibitory activity was observed in the nucleoside and steroid series, the best
      hit compounds in the 5-methyl pyrazol-3-one series showed low micromolar
      activity. We adapted our assay protocol to develop initial structure-activity
      relationships in this series, and to establish the target selectivity of the most
      potent inhibitor over two other glycosyltransferases. Our results provide
      insights into the activity of this class of non-substrate-like
      glycosyltransferase inhibitors, and highlight important general pitfalls for
      inhibitor screening against this enzyme family. Key elements of our experimental
      design, including a validated single-concentration protocol for inhibitor
      screening, and our process for elimination of false positives, are, in principle,
      directly transferable to many other sugar-nucleotide-dependent
      glycosyltransferases.

PMID- 30108905
TI  - Antitumor effect of sikokianin C, a selective cystathionine beta-synthase
      inhibitor, against human colon cancer in vitro and in vivo.
AB  - Cystathionine beta-synthase (CBS) overexpression is related to the proliferation
      and migration of human colon cancers. Targeted therapy that inhibits CBS has
      achieved promising effects in colon cancer treatments, but no selective inhibitor
      of CBS is available. In our previous study, a natural biflavonoid compound,
      sikokianin C, was identified as a potent and selective inhibitor of CBS. However,
      the mode of action of this compound and its antitumor efficacy in vivo remain
      unknown. In the present study, we have demonstrated that sikokianin C selectively
      inhibits CBS activity in a competitive manner, and the five key residues involved
      in the binding of sikokianin C to the substrate channel of CBS protein were
      identified via a combination of molecular docking and site-directed mutagenesis.
      Additionally, we analyzed the antitumor efficacy of sikokianin C against human
      colon cancer cells in vitro and in vivo. Sikokianin C greatly suppressed the
      proliferation of HT29 colon cancer cells with an IC50 value of 1.6 MUM, and CBS
      is the target of sikokianin C in mammalian cells, as evidenced by CBS knockdown
      analyses. Moreover, sikokianin C induced the apoptosis of HT29 cancer cells in a
      dose dependent manner. Treating mice with sikokianin C dramatically reduced the
      tumor volume and the weight of the colon cancer xenograft in vivo. These results
      indicate that the selective CBS inhibitor sikokianin C can potentially be used
      for the treatment of colon cancer.

PMID- 30108906
TI  - Novel cell-penetrating-amyloid peptide conjugates preferentially kill cancer
      cells.
AB  - The goal of this study was to develop a peptide which could use the toxic effects
      of amyloid, a substance which is the hallmark of over 25 known human diseases, to
      selectively kill cancer cells. Here we demonstrate that two separate amyloid
      forming hexapeptides, one from the microtubule associated protein Tau involved in
      formation of paired helical filaments of Alzheimer's disease, and the other an
      amyloid forming sequence from apolipoprotein A1, when conjugated to a cell
      penetrating peptide (CPP) sequence, form toxic oligomers which are stable for up
      to 14 h and able to enter cells by a combination of endocytosis and transduction.
      The amyloid peptide conjugates showed selective cytotoxicity to breast cancer,
      neuroblastoma and cervical cancer cells in culture compared to normal cells.
      Fluorescence imaging experiments showed the CPP-amyloid peptide oligomers formed
      intracellular fibrous amyloid, visible in the endosomes/lysosomes, cytosol and
      nucleus with thioflavin S (ThS) staining. Further experiments with rhodamine
      conjugated Dextran, propidium iodide (PI), and acridine orange (AO) suggested the
      mechanism of cell death was the permeability of the lysosomal membrane brought
      about by the formation of amyloid pores. Cytotoxicity could be abrogated by
      inhibitors of lysosomal hydrolases, consistent with a model where lysosomal
      hydrolases leak into the cytosol and induce cytotoxicity in subsequent downstream
      steps. Taken together, our data suggest that CPP-amyloid peptide conjugates show
      potential as a new class of anti-cancer peptides (ACPs).

PMID- 30108908
TI  - Design, synthesis and biological evaluation of tacrine-1,2,3-triazole derivatives
      as potent cholinesterase inhibitors.
AB  - We report herein the design and synthesis of a series of 11 novel tacrine-1,2,3
      triazole derivatives via a Cu(i)-catalyzed alkyne-azide 1,3-dipolar cycloaddition
      (CuAAC) reaction. The newly synthesized compounds were evaluated for their
      inhibition activity against Electrophorus electricus acetylcholinesterase (AChE)
      and horse serum butyrylcholinesterase (BChE) as potential drug targets for
      Alzheimer's disease (AD). Among the designed compounds, compound 8a2 exhibited
      potent inhibition against AChE and BChE with IC50 values of 4.89 MUM and 3.61
      MUM, respectively. Further structure-activity relationship (SAR) and molecular
      modeling studies may provide valuable insights into the design of better tacrine
      triazole analogues with potential therapeutic applications for AD.

PMID- 30108909
TI  - Design, synthesis and antibacterial evaluation of a polycationic calix[4]arene
      derivative alone and in combination with antibiotics.
AB  - The growing antibiotic resistance phenomenon continues to stimulate the search
      for new compounds and strategies to combat bacterial infections. In this study,
      we designed and synthesized a new polycationic macrocyclic compound (2) bearing
      four N-methyldiethanol ammonium groups clustered and circularly organized by a
      calix[4]arene scaffold. The in vitro activity of compound 2, alone and in
      combination with known antibiotics (ofloxacin, chloramphenicol or tetracycline),
      was assessed against strains of Staphylococcus aureus (ATCC 6538 and methicillin
      resistant isolate 15), S. epidermidis (ATCC 35984 and methicillin-resistant
      isolate 57), and Pseudomonas aeruginosa (ATCC 9027 and antibiotic-resistant
      isolate 1). Calix[4]arene derivative 2 showed significant antibacterial activity
      against ATCC and methicillin-resistant Gram positive Staphylococci, improved the
      stability of tetracycline in water, and in combination with antibiotics enhanced
      the antibiotic efficacy against Gram negative P. aeruginosa by an additive
      effect.

PMID- 30108911
TI  - Resistance-breaking profiling and gene expression analysis on an organometallic
      ReI-phenanthridine complex reveal parallel activation of two apoptotic pathways.
AB  - Emerging resistances of tumors against multiple anti-cancer agents are a major
      concern in the chemotherapeutical treatment of various cancers. Clearly, this
      raises the need for novel therapeutics with new modes of action. Herein, we
      report on the favorable in vitro anti-proliferative properties of a
      phenanthridine-containing ReI(CO)3 complex (compound 1, also abbreviated LR-166)
      and identify major contributions to its mode of action. The complex induces
      apoptosis in low micromolar concentrations even in drug-resistant Burkitt-like
      lymphoma (BJAB) and leukemia (Nalm-6) cell lines with known overexpression of p
      glycoproteins as was confirmed by measuring the amount of hypodiploid DNA via
      FACS Scan analysis. Importantly, a gene expression analysis in combination with
      toxicity studies on a number of modified cell lines (leukemia: NALM-6, lymphoma:
      BJAB, melanoma: MelHO) and the reduction of mitochondrial membrane potential
      (determined by adding JC-1 dye, followed by FACS analysis) confirmed the
      activation of both, the extrinsic and the intrinsic apoptotic pathway. Finally,
      the mechanism of action was shown not to be influenced by overexpression of the
      anti-apoptotic factor Bcl-2 in Mel-HO cells which are known to be resistant to a
      variety of drugs. All taken together, our experiments underscore the unique
      opportunities inherent in this novel lead structure of Re complexes to act as an
      effective chemotherapeutic agent in a combination therapy to overcome documented
      drug resistances in tumors.

PMID- 30108913
TI  - Targeting rare diseases.
AB  - Is working on genetic mutations that affect only a few in every thousand people a
      risky strategy?

PMID- 30108910
TI  - Synthesis and in vitro evaluation of substituted 3-cinnamoyl-4-hydroxy-pyran-2
      one (CHP) in pursuit of new potential antituberculosis agents.
AB  - Tuberculosis is an ever-evolving infectious disease that urgently needs new
      drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4
      hydroxy-6-methyl-2H-pyran-2-ones (CHPs) (2a-2y) was synthesized and evaluated
      against a standard virulent laboratory strain of Mycobacterium tuberculosis
      H37Rv. Out of 25 compounds, 11, 5, 7 and 2 (2a and 2u) showed least, moderate,
      good and appreciable activities, respectively, based on minimum inhibitory
      concentrations (MICs). Both 2a and 2u exhibited an MIC value of 4 MUg ml-1, which
      was close to those of standard antituberculosis drugs ethambutol, streptomycin
      and levofloxacin. Neither 2a nor 2u showed any activity against Gram-positive or
      Gram-negative bacteria and even against non-tuberculous mycobacterium, i.e.
      Mycobacterium smegmatis. Thus, like the antituberculosis drugs rifampicin,
      isoniazid and pretomanid, they are highly TB specific. All the pyrone-based
      chalcones showed no recognizable level of cytotoxicity against normal human
      kidney cell line (HEK-293) up to 80 MUM concentration and 11 exhibited an IC50 <=
      100 MUM (highest tested concentration). On further investigation, both 2a and 2u
      proved to be nontoxic against four human cell lines but 2a proved to be a better
      choice as it did not reach IC50 even at 100 MUM (highest tested concentration)
      while the IC50 of 2u was around 80 MUM. In conclusion, our results demonstrate
      that 2a is specific against M. tuberculosis with no appreciable toxicity; its
      activity matches that of some clinically approved antituberculosis drugs and it
      therefore merits further evaluation.

PMID- 30108912
TI  - Strigolactones: a plant phytohormone as novel anti-inflammatory agents.
AB  - Strigolactones (SLs) are a novel class of plant hormones with enormous potential
      for the prevention and treatment of inflammation. To further investigate the anti
      inflammatory activities of SLs, a representative SL, GR24, and the reductive
      products of its D-ring were synthesized and their anti-inflammatory activities
      were fully evaluated on both in vitro and in vivo models. Among these compounds,
      the two most active optical isomers (2a and 6a) demonstrated strong inhibitory
      activity on the release of inflammatory cytokines, including nitric oxide (NO),
      tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) by blocking the
      nuclear factor kappa B (NF-kappaB) and mitogen-activated protein kinase (MAPK)
      signaling pathways; they also greatly inhibited the migration of neutrophils and
      macrophages in fluorescent protein labeled zebrafish larvae. These results
      identified the promising anti-inflammatory effects of SLs, and suggested that
      both the absolute configuration of SL and the alpha,beta-unsaturated D-ring
      structure are essential for the observed anti-inflammatory activity.

PMID- 30108914
TI  - Synthesis of biologically active boron-containing compounds.
AB  - Boron-containing compounds which possess unique and attractive properties have
      received increasing attention from the pharmaceutical industry and academia
      recently. They have shown interesting and useful biological activities, including
      antibacterial, antifungal, antiparasitic, antiviral, and anti-inflammatory
      activities. In this review, the synthetic strategies for various boron-containing
      compounds, including peptidyl boronic acids, benzoxaboroles, benzoxaborines,
      benzodiazaborines, amine carboxyboranes, and amine cyanoboranes are summarized.
      Representative structures of each structural class and recently developed
      biologically active boron-containing compounds are used as examples in this
      review.

PMID- 30108917
TI  - A novel allosteric inhibitor that prevents IKKbeta activation.
AB  - I kappa B kinase beta (IKKbeta) is one of the primary targets to regulate
      canonical NF-kappaB activity. The misregulation of NF-kappaB is associated with
      various diseases, including chronic inflammation and cancers. Most of the known
      IKKbeta inhibitors target its active form and suffer from poor selectivity. In
      the present study, we aim to design inhibitors that can bind to the IKKbeta
      inactive form and block its activation. We identified a potential allosteric site
      between the kinase domain (KD) and ubiquitin-like domain (ULD) of human IKKbeta
      and used it to virtually screen a chemical library for allosteric inhibitors.
      Among the 133 compounds tested, 16 inhibited NF-kappaB activity by over 50% at 50
      MUM in a reporter gene assay. Further quantitative measurements and cytotoxicity
      study gave one compound 124 (3,4-dichloro-2-ethoxy-N-(2,2,6,6
      tetramethylpiperidin-4-yl)benzenesulfonamide) which specifically targets the
      IKKbeta inactive form. In cells, 124 inhibited IkappaBalpha phosphorylation and
      NF-kappaB transcriptional activity for the reporter gene with an IC50 of 35 MUM
      by decreasing the phosphorylation level of Ser177/181 on IKKbeta and blocking its
      activation upon TNFalpha stimulation. Molecular dynamics simulations demonstrated
      that 124 binds to the pocket between KD and ULD in the inactive conformation of
      IKKbeta rather than the active conformation. As the first allosteric inhibitor
      that prevents IKKbeta activation, 124 provides a good starting point for further
      inhibitor discovery and a probe for IKKbeta enzyme cycle and regulatory mechanism
      study.

PMID- 30108915
TI  - Recent development of lipoxygenase inhibitors as anti-inflammatory agents.
AB  - Inflammation is favorable in most cases, because it is a kind of body defensive
      response to external stimuli; sometimes, inflammation is also harmful, such as
      attacks on the body's own tissues. It could be that inflammation is a unified
      process of injury and resistance to injury. Inflammation brings extreme pain to
      patients, showing symptoms of rubor, swelling, fever, pain and dysfunction. As
      the specific mechanism is not clear yet, the current anti-inflammatory agents are
      given priority for relieving suffering of patients. Thus it is emergent to find
      new anti-inflammatory agents with rapid effect. Lipoxygenase (LOX) is a kind of
      rate-limiting enzyme in the process of arachidonic acid metabolism into
      leukotriene (LT) which mediates the occurrence of inflammation. The inhibition of
      LOX can reduce LT, thereby producing an anti-inflammatory effect. In this review,
      the LOX inhibitors reported in recent years are summarized, and, in particular,
      their activities, structure-activity relationships and molecular docking studies
      are emphasized, which will provide new ideas to design novel LOX inhibitors.

PMID- 30108918
TI  - Allenamide as a bioisostere of acrylamide in the design and synthesis of targeted
      covalent inhibitors.
AB  - The success of acrylamide-containing drugs in treating cancers has spurred a
      passion to search for acrylamide bioisosteres. In our endeavour, we have
      identified that an allenamide group can be a reactive bioisostere of the
      acrylamide group. In our development of allenamide-containing compounds, we found
      that the most potent compound, 14, inhibited the kinase activities of both
      T790M/L858R double mutant and wild type EGFR in a low nM range. 14 also inhibited
      the growth of NCI-H1975 lung cancer cells at IC50 = 33 nM, which is comparable to
      that of acrylamide-containing osimertinib. The western blot analysis showed that
      the phosphorylation of EGFR, AKT, and ERK1/2 was simultaneously inhibited in a
      dose-dependent manner when NCI-H1975 cells were treated with 14. By measuring the
      conjugate addition product formed by 14 and GSH, we obtained a reaction rate
      constant of 302.5 * 10-3 min-1, which is about 30-fold higher than that of
      osimertinib. Taken together, our data suggest that the allenamide-containing
      compounds inhibited EGFR kinases through covalent modifications. Our study
      indicates that the allenamide group could serve as an alternative electrophilic
      warhead in the design of targeted covalent inhibitors, and this bioisostere
      replacement may have broad applications in medicinal chemistry.

PMID- 30108916
TI  - Applications and perspectives of nanomaterials in novel vaccine development.
AB  - Vaccines show great potential for both prophylactic and therapeutic use in
      infections, cancer, and other diseases. With the rapid development of bio
      technologies and materials sciences, nanomaterials are playing essential roles in
      novel vaccine formulations and can boost antigen effectiveness by operating as
      delivery systems to enhance antigen processing and/or as immune-potentiating
      adjuvants to induce or potentiate immune responses. The effect of nanoparticles
      in vaccinology showed enhanced antigen stability and immunogenicity as well as
      targeted delivery and slow release. However, obstacles remain due to the lack of
      fundamental knowledge on the detailed molecular working mechanism and in vivo bio
      effects of nanoparticles. This review provides a broad overview of the current
      improvements in nanoparticles in vaccinology. Modern nanoparticle vaccines are
      classified by the nanoparticles' action based on either delivery system or immune
      potentiator approaches. The mechanisms of interaction of nanoparticles with the
      antigens and the immune system are discussed. Nanoparticle vaccines approved for
      use are also listed. A fundamental understanding of the in vivo bio-distribution
      and the fate of nanoparticles will accelerate the rational design of new
      nanoparticles comprising vaccines in the future.

PMID- 30108919
TI  - Polyphenols from Ilex latifolia Thunb. (a Chinese bitter tea) exert anti
      atherosclerotic activity through suppressing NF-kappaB activation and
      phosphorylation of ERK1/2 in macrophages.
AB  - Ilex latifolia Thunb is a kind of herbal tea and widely consumed as a functional
      tea beverage in Asian countries. In this study, polyphenols were extracted from
      I. latifolia and the major compounds were identified by liquid chromatography
      mass spectrometry (LC-MS), then the effect on oxidized low-density lipoprotein
      (ox-LDL)-induced macrophage foam cell formation was investigated. Results showed
      that the polyphenols could significantly inhibit ox-LDL-induced macrophage foam
      cell formation and suppress lipid droplet accumulation and cholesterol uptake in
      RAW 264.7 cells. Additionally, the secretion of pro-inflammatory cytokines, such
      as tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta, IL-6 and inducible
      nitric oxide synthase (iNOS), was significantly inhibited. Moreover, the
      polyphenols could suppress the expression of lectin-like oxidized low-density
      lipoprotein receptor-1 (LOX-1) and clusters of differentiation 36 (CD 36), which
      were receptors for ox-LDL. Mechanistically, I. latifolia polyphenols could
      inhibit macrophage foam cell formation by suppressing NF-kappaB activation and
      phosphorylation of ERK1/2.

PMID- 30108920
TI  - Hepatocellular targeted alpha-tocopherol based pH sensitive galactosylated
      lipids: design, synthesis and transfection studies.
AB  - Receptor mediated gene delivery to the liver offers advantages in treating
      genetic disorders such as hemophilia and hereditary tyrosinemia type I (HTI).
      Prior findings demonstrated that tethering the d-galactose head group to cationic
      lipids directs genes to the liver via asialoglycoprotein receptors (ASGPRs). In
      our continued efforts to develop safer and efficient lipofectins, we demonstrated
      that cationic lipids bearing alpha-tocopherol, an antioxidant, as a hydrophobic
      domain could deliver genes efficiently with high safety profiles in multiple cell
      lines. Towards developing ASGPR targeted pH sensitive cationic lipids, we have
      designed a galactosylated cationic lipid (Toc-Gal) with alpha-tocopherol as the
      hydrophobic core covalently connected with a pH responsive triazole moiety and a
      non-targeting control lipid (Toc-OH) without the galactose head group. In this
      study, we present the design and synthesis of a pH sensitive galactosylated
      cationic lipid (Toc-Gal), its comparative transfection biology, cellular uptake
      studies, serum stability and cytotoxicity profiles in both ASGPR positive and
      negative liver cells, i.e. HepG2 and SK-Hep-1, respectively.

PMID- 30108921
TI  - New (3-(1H-benzo[d]imidazol-2-yl))/(3-(3H-imidazo[4,5-b]pyridin-2-yl))-(1H-indol
      5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization
      inhibitors.
AB  - A series of new (3-(1H-benzo[d]imidazol-2-yl))/(3-(3H-imidazo[4,5-b]pyridin-2
      yl))-(1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates 4-6(a-i) were
      synthesized and evaluated for their antiproliferative activity on selected human
      cancer cell lines such as prostate (DU-145), lung (A549), cervical (HeLa) and
      breast (MCF-7). Most of these conjugates showed considerable cytotoxicity with
      IC50 values ranging from 0.54 to 31.86 MUM. Among them, compounds 5g and 6f
      showed significant activity against human prostate cancer cell line DU-145 with
      IC50 values of 0.68 MUM and 0.54 MUM, respectively. Tubulin polymerization assay
      and immunofluorescence analysis results suggest that these compounds effectively
      inhibit microtubule assembly formation in DU-145. Further, the apoptosis-inducing
      ability of these derivatives (5g and 6f) was confirmed by Hoechst staining,
      measurement of mitochondrial membrane potential and ROS generation and annexin V
      FITC assays.

PMID- 30108922
TI  - Synthesis, characterization and biological application of 5-quinoline 1,3,5
      trisubstituted pyrazole based platinum(ii) complexes.
AB  - Square planar mononuclear platinum(ii) complexes were synthesized in the presence
      of neutral bidentate heterocyclic (5-quinoline 1,3,5-tri-substituted pyrazole
      scaffold) ligands and K2PtCl4 salt. The synthesized compounds were characterized
      by micro-elemental analysis, FT-IR, UV-vis, 1H NMR, 13C NMR, TGA, mass
      spectrometry and molar conductivity. Their biological activities were
      investigated by in vitro brine shrimp lethality bioassay, in vitro antimicrobial
      study against five different pathogens, in vivo cellular level cytotoxicity
      against Schizosaccharomyces pombe cells, and in vitro anti-proliferation assay.
      The binding constant Ksv, Kb, Ka values of the complexes were determined by DNA
      interaction studies. The gel electrophoresis assay was carried out to examine the
      effect of the complexes on the DNA nuclease of pUC19 plasmid DNA. The docking
      energies of the ligands (L1-L5 ) and complexes (I-V) were observed in the range
      of -265.14 to -284.33 kJ mol-1. The synthesized Pt(ii) complexes (I-V) were
      screened against the MCF-7 (human breast adenocarcinoma) and HCT-116 (human colon
      carcinoma) cancer cell lines.

PMID- 30108923
TI  - Antiproliferative activity of novel isatinyl/indanyl nitrones (INs) as potential
      spin trapping agents of free radical intermediates.
AB  - A series of ketonitrones derived from isatin and indanone (INs) were synthesized
      and evaluated for their antiproliferative activities against several human cancer
      cell lines. Then, the antioxidant properties of these substrates were measured by
      the DPPH test to report their biological activity in terms of their spin trapping
      action. In particular, one substrate has showed very high biological and
      scavenging activity, probably due to the strong correlation between its spin
      trapping activity and structure.

PMID- 30108924
TI  - Design, synthesis and biological evaluation of 3',4',5'-trimethoxy flavonoid
      benzimidazole derivatives as potential anti-tumor agents.
AB  - A series of 3',4',5'-trimethoxy flavonoids with benzimidazole linked by different
      chain alkanes have been designed and synthesized. The potential activity of these
      compounds as anti-tumor agents was evaluated by cytotoxicity assay in MGC-803
      (human gastric cancer), MCF-7 (human breast cancer), HepG-2 (human hepatoma) and
      MFC (mouse gastric cancer) tumor cell lines. Among them, compound 15 7-(3-(2
      chloro-1H-benzo[d]imidazol-1-yl)propoxy)-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4
      one displayed the most potent antiproliferative activity, with IC50 values of
      20.47 +/- 2.07, 43.42 +/- 3.56, 35.45 +/- 2.03 MUM and 23.47 +/- 3.59 MUM,
      respectively. The flow cytometry (FCM) results showed that compound 15 caused the
      cell cycle to be arrested in G1 phase and induced apoptosis of MFC cells in a
      dose-dependent manner. In addition, compound 15 exhibited a significant
      inhibitory effect on tumor growth in vivo. All the results outlined the great
      potential of compound 15 for further exploitation as anti-tumor agent.

PMID- 30108925
TI  - Molecular modeling study, synthesis and biological evaluation of combretastatin A
      4 analogues as anticancer agents and tubulin inhibitors.
AB  - As the major structural component of microtubules, tubulin is an interesting
      target for the development of anticancer agents. In this study, 64 tubulin
      polymerization inhibitors of five-membered heterocycle-based combretastatin A-4
      analogues were studied by a combination of molecular modeling techniques
      including 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation. The
      CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular
      similarity indices analysis) models were established with desirable statistical
      parameters and excellent predictive ability. 20 ns MD simulations were
      successfully performed to confirm the detailed binding mode and validate the
      rationality of docking results. Combining the binding free energy calculations
      and 3D-QSAR results, some new heterocycle-based combretastatin A-4 analogues were
      designed. Three of them were synthesized and biologically evaluated. Compound 13a
      displayed potent antiproliferative activity (IC50 value of 1.31 MUM against HepG2
      cells, IC50 value of 1.37 MUM against A549 cells) and inhibition of tubulin
      polymerization activity (IC50 value of 0.86 MUM). Compound 13b also presented
      good activity against HepG2 cells (IC50 value of 4.75 MUM). The experimental
      results demonstrated that the built models were effective for the development of
      novel anticancer agents and tubulin inhibitors.

PMID- 30108926
TI  - Design, synthesis and bioactivities of phenithionate analogues or derivatives for
      anti-schistosomiasis.
AB  - A novel series of phenithionate analogues or derivatives were designed and
      synthesized using phenithionate as the lead compound, and their bioactivities
      were studied. Their structures were confirmed by 1H NMR, 13C NMR, HR-ESI-MS, and
      elemental analysis, respectively. The results of in vitro inhibitory activity
      measurement proved that compounds 5a, 5c, 5g, 5i, 5m and 5o had a better
      inhibitory effect on larva and imago schistosoma. Among them, the inhibitory
      activity of compound 5i for larva schistosoma was IC50 = 5.21 +/- 0.04 MUg mL-1,
      and for imago schistosoma it was IC50 = 6.35 +/- 0.08 MUg mL-1. Moreover, the
      experimental results of in vivo anti-schistosomiasis activity measurement showed
      that they had good anti-schistosomiasis activity. Therefore, these compounds had
      better drugability.

PMID- 30108927
TI  - DNA interactions and in vitro anticancer evaluations of pyridine-benzimidazole
      based Cu complexes.
AB  - Copper is an essential element and has redox potential, thus copper complexes
      have been developed rapidly with the hope of curing cancer. To further develop
      anticancer agents and investigate their anticancer mechanisms, two Cu complexes,
      [Cu(bpbb)0.5.Cl.SCN].(CH3OH) (1) and [Cu2(bpbb).Br3.(OH)] n (2), were synthesized
      and characterized using 4,4'-bis((2-(pyridin-2-yl)-1H-benzo[d]imidazol-1
      yl)methyl)biphenyl (bpbb), with associated Cu(ii) salts. Complex 1 is a binuclear
      structure, whereas 2 is a one-dimensional complex. Compared with 2, complex 1
      exhibited potent in vitro cytotoxicity toward four cell lines (HCT116, BGC823,
      HT29, and SMMC7721), and was most effective against HCT116 cells. Therefore,
      further in-depth investigation was carried out using complex 1. Absorption
      spectral titration experiments, ethidium bromide displacement assays, and
      circular dichroism spectroscopic studies suggested that complex 1 binds strongly
      to DNA by intercalation. Complex 1 exhibited a clear concentration-dependent
      pBR322 DNA cleavage activity. Inductively coupled plasma mass spectrometry
      testing implied that complex 1 could enter cells and that DNA was one important
      target. Cellular level assays suggested that complex 1 activates the generation
      of intracellular reactive oxygen species, causing DNA damage, promoting cell
      cycle arrest and mitochondria dysfunction, and inducing cellular apoptosis.

PMID- 30108928
TI  - Rational design and characterization of a DNA/HDAC dual-targeting inhibitor
      containing nitrogen mustard and 2-aminobenzamide moieties.
AB  - Histone deacetylases (HDACs) play a key role not only in gene expression but also
      in DNA repair. Herein, we report the rational design and characterization of a
      compound named chlordinaline containing nitrogen mustard and 2-aminobenzamide
      moieties as a DNA/HDAC dual-targeting inhibitor. Chlordinaline exhibited moderate
      total HDAC inhibitory activity. The HDAC isoform selectivity assay indicated that
      chlordinaline mostly inhibits HDAC3. Chlordinaline exhibited both DNA and HDAC
      inhibitory activities and showed potent antiproliferative activity against all
      the six test cancer cell lines with IC50 values of as low as 3.1-14.2 MUM, which
      is significantly more potent than reference drugs chlorambucil and tacedinaline.
      Chlordinaline could induce the apoptosis and G2/M phase cell cycle arrest of A375
      cancer cells. This study demonstrates that combining nitrogen mustard and 2
      aminobenzamide moieties into one molecule is an effective method to obtain
      DNA/HDAC dual-targeting inhibitors as potent antitumor agents. Chlordinaline as
      the first example of such DNA/HDAC dual-targeting inhibitors could be a promising
      candidate for cancer therapy and could also be a lead compound for further
      optimization.

PMID- 30108929
TI  - Discovery of 7-hydroxyaporphines as conformationally restricted ligands for beta
      1 and beta-2 adrenergic receptors.
AB  - A series of (-)-nornuciferidine derivatives was synthesized and the non-natural
      enantiomer of the aporphine alkaloid was discovered to be a potent beta1- and
      beta2-adrenergic receptor ligand that antagonized isoproterenol and procaterol
      induced cyclic AMP increases from adenylyl cyclase, respectively. Progressive
      deconstruction of the tetracyclic scaffold to less complex cyclic and acyclic
      analogues revealed that the conformationally restricted (6a-R,7-R)-7
      hydroxyaporphine 2 (AK-2-202) was necessary for efficient receptor binding and
      antagonism.

PMID- 30108930
TI  - Design, synthesis and evaluation of indole derivatives as multifunctional agents
      against Alzheimer's disease.
AB  - A series of indole derivatives was designed and synthesised to improve on
      activity and circumvent pharmacokinetic limitations experienced with the
      structurally related compound, ladostigil. The compounds consisted of a
      propargylamine moiety (a known MAO inhibitor and neuroprotector) at the N1
      position and a ChE inhibiting diethyl-carbamate/urea moiety at the 5 or 6
      position of the indole ring. In order to prevent or slow down the in vivo
      hydrolysis and deactivation associated with the carbamate function of ladostigil,
      a urea moeity was incorporated into selected compounds to obtain more
      metabolically stable structures. The majority of the synthesised compounds showed
      improved MAO-A inhibitory activity compared to ladostigil. The compounds
      possessing the propargylamine moiety showed good MAO-B inhibitory activity with 6
      and 8 portraying IC50 values between 14-20 fold better than ladostigil. The ChE
      assay results indicated that the compounds have non-selective inhibitory
      activities on eeAChE and eqBuChE regardless of the type or position of
      substitution (IC50: 2-5 MUM). MAO-A and MAO-B docking results showed that the
      propargylamine moiety was positioned in close proximity to the FAD cofactor
      suggesting that the good inhibitory activity may be attributed to the
      propargylamine moiety and irreversible inhibition as confirmed in the
      reversibility studies. Docking results also indicated that the compounds have
      interactions with important amino acids in the AChE and BuChE catalytic sites.
      Compound 6 was the most potent multifunctional agent showing better inhibitory
      activity than ladostigil in vitro on all enzymes tested (hMAO-A IC50 = 4.31 MUM,
      hMAO-B IC50 = 2.62 MUM, eeAChE IC50 = 3.70 MUM, eqBuChE IC50 = 2.82 MUM).
      Chemical stability tests confirmed the diethyl-urea containing compound 6 to be
      more stable than its diethyl-carbamate containing counterpart compound 8.
      Compound 6 also exerted significant neuroprotection (52.62% at 1 MUM) against
      MPP+ insult to SH-SY5Y neural cells and has good in silico predicted ADMET
      properties. The favourable neuronal enzyme inhibitory activity, likely improved
      pharmacokinetic properties in vivo and the potent neuroprotective ability of
      compound 6 make it a promising compound for further development.

PMID- 30108931
TI  - Identification of karanjin isolated from the Indian beech tree as a potent CYP1
      enzyme inhibitor with cellular efficacy via screening of a natural product
      repository.
AB  - CYP1A1 is thought to mediate carcinogenesis in oral, lung and epithelial cancers.
      In order to identify a CYP1A1 inhibitor from an edible plant, 394 natural
      products in the IIIM's natural product repository were screened, at 10 MUM
      concentration, using CYP1A1-SacchrosomesTM (i.e. microsomal enzyme isolated from
      recombinant baker's yeast). Twenty-seven natural products were identified that
      inhibited 40-97% of CYP1A1's 7-ethoxyresorufin-O-deethylase activity. The IC50
      values of the 'hits', belonging to different chemical scaffolds, were determined.
      Their selectivity was studied against a panel of 8 CYP-SacchrosomesTM. In order
      to assess cellular efficacy, the 'hits' were screened for their capability to
      inhibit CYP enzymes expressed within live recombinant human embryonic kidney
      (HEK293) cells from plasmids encoding specific CYP genes (1A2, 1B1, 2C9, 2C19,
      2D6, 3A4). Isopimpinellin (IN-475; IC50, 20 nM) and karanjin (IN-195; IC50, 30
      nM) showed the most potent inhibition of CYP1A1 in human cells. Isopimpinellin is
      found in celery, parsnip, fruits and in the rind and pulp of limes whereas
      different parts of the Indian beech tree, which contain karanjin, have been used
      in traditional medicine. Both isopimpinellin and karanjin negate the cellular
      toxicity of CYP1A1-mediated benzo[a]pyrene. Molecular docking and molecular
      dynamic simulations with CYP isoforms rationalize the observed trends in the
      potency and selectivity of isopimpinellin and karanjin.

PMID- 30108932
TI  - MicroRNAs as novel endogenous targets for regulation and therapeutic treatments.
AB  - MicroRNAs (miRNAs) are small non-coding RNAs that have been identified as key
      endogenous biomolecules that are able to regulate gene expression at the post
      transcriptional level. The abnormal expression or function of miRNAs has been
      demonstrated to be closely related to the occurrence or development of various
      human diseases, including cancers. Regulation of these abnormal miRNAs thus holds
      great promise for therapeutic treatments. In this review, we summarize exogenous
      molecules that are able to regulate endogenous miRNAs, including small molecule
      regulators of miRNAs and synthetic oligonucleotides. Strategies for screening
      small molecule regulators of miRNAs and recently reported small molecules are
      introduced and summarized. Synthetic oligonucleotides including antisense miRNA
      oligonucleotides and miRNA mimics, as well as delivery systems for these
      synthetic oligonucleotides to enter cells, that regulate endogenous miRNAs are
      also summarized. In addition, we discuss recent applications of these small
      molecules and synthetic oligonucleotides in therapeutic treatments. Overall, this
      review aims to provide a brief synopsis of recent achievements of using both
      small molecule regulators and synthetic oligonucleotides to regulate endogenous
      miRNAs and achieve therapeutic outcomes. We envision that these regulators of
      endogenous miRNAs will ultimately contribute to the development of new therapies
      in the future.

PMID- 30108933
TI  - Heterocyclic Schiff base transition metal complexes in antimicrobial and
      anticancer chemotherapy.
AB  - In recent years, the number of people suffering from cancer and multidrug
      resistant infections has sharply increased, leaving humanity without any choice
      but to search for new treatment options and strategies. Although cancer is
      considered the leading cause of death worldwide, it also paves the way many
      microbial infections and thus increases this burden manifold. Development of
      small molecules as anticancer and anti-microbial agents has great potential and a
      plethora of drugs are already available to combat these diseases. However, the
      wide occurrence of multidrug resistance in both cancer and microbial infections
      necessitates the development of new and potential molecules with desired
      properties that could circumvent the multidrug resistance problem. A successful
      strategy in anticancer chemotherapy has been the use of metallo-drugs and this
      strategy has the potential to be used for treating multidrug-resistant infections
      more efficiently. As a class of molecules, Schiff bases have been the topic of
      considerable interest, owing to their versatile metal chelating properties,
      inherent biological activities and flexibility to modify the structure to fine
      tune it for a particular biological application. Schiff base-based metallo-drugs
      are being researched to develop new anticancer and anti-microbial chemotherapies
      and because both anticancer and anti-microbial targets are different,
      heterocyclic Schiff bases can be structurally modified to achieve the desired
      molecule, targeting a particular disease. In this review, we collect the most
      recent and relevant literature concerning the synthesis of heterocyclic Schiff
      base metal complexes as anticancer and anti-microbial agents and discuss the
      potential and future of this class of metallo-drugs as either anticancer or anti
      microbial agents.

PMID- 30108934
TI  - Recent updates in the discovery and development of novel antimalarial drug
      candidates.
AB  - Though morbidity and mortality due to malaria have declined in the last 15 years,
      emerging resistance to first-line artemisinin-based antimalarials, absence of
      efficacious vaccines and limited chemotherapeutic alternatives imperil the
      consolidation of these gains. As a blueprint to steer future designs of new
      medicines, malaria drug discovery recently adopted a descriptive proposal for the
      ideal candidate molecules and drugs likely to successfully progress into the
      final stages of clinical development. As an audit of recent developments in the
      chemotherapy of malaria in the last five years, this review captures a landscape
      of diverse molecules at various stages of drug development and discusses their
      progress. In brief, we also discuss how omics data on Plasmodium has been
      extensively leveraged to identify potential vaccine candidates and putative
      targets of molecules in development and clinical use as well as map loci implicit
      in their modes of resistance. Future perspective on malaria drug development
      should involve a reconciliation of some of the challenges of the target candidate
      profiles (TCPs), specifically TCP3, with the promise of effective anti-hypnozoite
      medicines. Similarly, with the recent development of a humanized mouse model that
      can evaluate the prophylactic potential of candidate drugs, we argue for
      increased effort at identifying more liver-stage molecules, which are often only
      secondarily prioritized in conventional screening programs.

PMID- 30108936
TI  - Oral drug suitability parameters.
AB  - Assessing the oral drug suitability of compounds as early as possible within drug
      discovery is an important objective. This study describes a methodology that
      attempts to simplify the evaluation of compounds based on their in vivo quantity
      levels within a mammalian body, represented using a mathematical model that
      imposes a time limitation on oral absorption and assumes non-instantaneous drug
      distribution between plasma and tissue. This simplification results in two new
      oral drug suitability parameters that can quantitatively relate oral dose to in
      vivo exposure for compounds with vastly different tendencies in terms of
      absorption into, and elimination from, the body. Consequently, the complexities
      associated with evaluating a compound's oral drug suitability are simplified to
      an assessment of these two new parameters. Application of this methodology at the
      virtual design stage is discussed, along with functionality that accounts for
      uncertainty related to a compound's distribution kinetics and errors associated
      to in silico QSAR predictions for the required input data.

PMID- 30108935
TI  - Automated synthesis of [68Ga]oxine, improved preparation of 68Ga-labeled
      erythrocytes for blood-pool imaging, and preclinical evaluation in rodents.
AB  - Radiolabeled erythrocytes have multiple applications in nuclear medicine,
      including blood pool imaging. Historically they have been labeled with SPECT
      radionuclides. A PET blood pool imaging agent is highly desirable as it would
      improve clinical applications with better image quality and resolution, higher
      sensitivity, and dynamic scanning capabilities. With the coming of age of modern
      68Ge/68Ga generator systems, gallium-68 is now widely accessible. In this paper
      we describe an updated method for the preparation of 68Ga-labeled erythrocytes
      and their preliminary use in rodent blood pool imaging. A novel automated
      synthesis of [68Ga]oxine using a 68Ga/68Ge generator and automated synthesis
      module is reported. [68Ga]Oxine was synthesized in 50 +/- 5% (n = 3) non-decay
      corrected radiochemical yield and >99% radiochemical purity. Rat and human
      erythrocytes were successfully labeled with the complex in 42% RCY, and the 68Ga
      labeled erythrocytes have been shown to clearly image the blood pool in a healthy
      rat. Human erythrocytes labelled with [68Ga]oxine were shown to be viable up to 2
      hours post-labelling, and washout of the radiolabel was minimal up to 1 hour post
      labelling. Further optimization of the labeling method to translate for use in
      human cardiac and oncologic blood pool PET imaging studies, is underway.

PMID- 30108937
TI  - Design, synthesis and biological evaluation of novel 5-hydroxy-2-methyl-4H-pyran
      4-one derivatives as antiglioma agents.
AB  - d-2-Hydroxyglutarate (d-2HG) is frequently found in human brain cancers.
      Approximately 50-80% of grade II glioma patients have a high level of d-2HG
      production, which can lead to cancer initiation. In this study, a series of novel
      5-hydroxy-2-methyl-4H-pyran-4-one derivatives were designed and synthesized as
      antiglioma agents, and their related structure-activity relationships are
      discussed. Among these novel compounds, 4a exhibited promising anti-proliferative
      activity against glioma HT1080 cells and U87 cells with an IC50 of 1.43 MUM and
      4.6 MUM, respectively. Further studies found that the most active compound (4a)
      shows an 86.3% inhibitory rate against the intracellular production of d-2HG at 1
      MUM, and dramatic inhibitory effects, even at 1 MUM on the colony formation and
      migration of U87 and HT1080 cells.

PMID- 30108938
TI  - Design, synthesis and evaluation of (R)-3-(7-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4
      yl)amino)-5-azaspiro[2.4]heptan-5-yl)-3-oxopropanenitrile as a JAK1-selective
      inhibitor.
AB  - Based on (R)-N-methyl-N-(5-azaspiro[2.4]heptan-7-yl)-7H-pyrrolo[2,3-d]pyrimidin-4
      amine as a core scaffold, we identified (R)-3-(7-(methyl(7H-pyrrolo[2,3
      d]pyrimidin-4-yl)amino)-5-azaspiro[2.4]heptan-5-yl)-3-oxopropanenitrile [(R)-6c]
      as a JAK1 selective inhibitor. The structural design was based on the combination
      of tofacitinib's 7-deazapurine and 5-azaspiro[2.4]heptan-7-amine. Compound (R)-6c
      exhibited an IC50 value of 8.5 nM against JAK1 with a selectivity index of 48
      over JAK2. To optimize (R)-6c as a lead compound, we performed in vitro ADME,
      hERG, kinase profiling, and pharmacokinetic tests. Mouse and rat in vivo studies
      verified that (R)-6c exhibited desired efficacies in CIA and AIA models.

PMID- 30108939
TI  - 5,6-Benzoflavones as cholesterol esterase inhibitors: synthesis, biological
      evaluation and docking studies.
AB  - In a continued effort to develop potent cholesterol esterase (CEase) inhibitors,
      a series of 5,6-benzoflavone derivatives was rationally designed and synthesized
      by changing the position of the benzene ring attached to the flavone skeleton in
      previously reported 7,8-benzoflavones. All the synthesized compounds were checked
      for their inhibitory potential against cholesterol esterase (CEase) using a
      spectrophotometric assay. Among the series of forty compounds, seven derivatives
      (B-10 to B-16) exhibited above 90 percent inhibition against CEase in an in vitro
      enzymatic assay. Compound B-16 showed the most promising activity with an IC50
      value of 0.73 nM against cholesterol esterase. To determine the type of
      inhibition, enzyme kinetic studies were carried out for B-16, which revealed its
      mixed-type inhibition approach. Moreover, to figure out the key binding
      interactions of B-16 with the amino acid residues of the enzyme's active site,
      molecular protein-ligand docking studies were also performed. B-16 completely
      blocks the catalytic assembly of CEase and prevents it from participating in the
      ester hydrolysis mechanism. The favorable binding conformation of B-16 suggests
      its prevailing role as a CEase inhibitor. Overall, the study showed that the cis
      orientation of ring A with respect to the carbonyl group of ring C is responsible
      for the potent CEase inhibitory activity of the newly synthesized compounds.

PMID- 30108940
TI  - Exploring eukaryotic versus prokaryotic ribosomal RNA recognition with
      aminoglycoside derivatives.
AB  - New derivatives of aminoglycosides containing 6'-carboxylic acid or 6'-amide on
      their ring I were designed, synthesized and their ability to readthrough nonsense
      mutations was examined in vitro, along with the protein translation inhibition in
      prokaryotic and eukaryotic systems. The observed structure-activity
      relationships, along with the comparative molecular dynamics simulations within
      the eukaryotic rRNA decoding site, showed high sensitivity of 6'-position to
      substitution, indicating that the rational design of potent stop-codon read
      through inducers requires consideration of not only the structure and energetics
      of the drug-RNA interaction but also the dynamics associated with that
      interaction.

PMID- 30108941
TI  - Membrane-active antimicrobial poly(amino-modified alkyl) beta-cyclodextrins
      synthesized via click reactions.
AB  - The emergence of drug-resistant bacteria has led to the high demand for new
      antibiotics. In this report, we investigated membrane-active antimicrobial beta
      cyclodextrins. These contain seven amino-modified alkyl groups on a molecule,
      which act as functional moieties to permeabilize bacterial cell membranes. The
      polyfunctionalization of cyclodextrins was achieved through a click reaction
      assisted by microwave irradiation. A survey using derivatives with systematically
      varied functionalities clarified the unique correlation of the antimicrobial
      activity of these compounds with their molecular structure and
      hydrophobicity/hydrophilicity balances. The optimum hydrophobicity for the
      compounds being membrane-active was specific to bacterial strains and animal
      cells; this led to specific compounds having selective toxicity against bacteria
      including multidrug-resistant pathogens. The results demonstrate that
      cyclodextrin is a versatile molecular scaffold for rationally designed structures
      and can be used for the development of new antibiotics.

PMID- 30108942
TI  - Structure-guided design of a potent peptide inhibitor targeting the interaction
      between CRK and ABL kinase.
AB  - CT-10 regulator of kinase (CRK) proteins play important roles in human cancer
      metastasis and invasion. Moreover, CRK proteins are the major phosphorylation
      substrates of ABL kinase and its oncogenic mutant BCR-ABL kinase. The interaction
      between CRK and BCR-ABL plays important roles in chronic myeloid leukemia. Hence,
      inhibiting the interaction of CRK with BCR-ABL is an attractive way to attenuate
      cancer metastasis. Herein, we report the development of a peptide inhibitor, PRM
      3, targeting the interaction between CRK-II and ABL kinase. PRM-3 binds to the N
      terminal SH3 (nSH3) domain in CRK-II with a 10 nM affinity and prevents the
      interaction between CRK-II and ABL kinase. An in vitro biochemical assay
      demonstrated that PRM-3 inhibits the ABL-dependent phosphorylation of CRK-II more
      effectively than imatinib. Remarkably, PRM-3 also inhibited the CRK
      phosphorylation by T315I-ABL kinase, which is resistant to all first- and second
      generation tyrosine kinase inhibitors. Our study provides a promising alternative
      approach to overcome the drug resistance of ABL kinase.

PMID- 30108944
TI  - Novel valdecoxib derivatives by ruthenium(ii)-promoted 1,3-dipolar cycloaddition
      of nitrile oxides with alkynes - synthesis and COX-2 inhibition activity.
AB  - Novel valdecoxib-based cyclooxygenase-2 inhibitors were synthesized in one step
      via 1,3-dipolar cycloaddition of nitrile oxides with a series of eleven aryl
      alkynes, six of them described for the first time. Application of Ru(ii)
      catalysis leads preferably to the formation of the 3,4-diaryl-substituted
      isoxazoles, while under thermal heating with base the 3,5-diaryl substitution
      pattern is favoured. The new the 3,4-diaryl-substituted isoxazoles possessing a
      small substituent (H and Me) displayed high COX-2 inhibition affinity (IC50 =
      0.042-0.073 MUM) and excellent selectivity (COX-2 SI > 2000). In contrast, the
      3,5-diaryl substituted compounds displayed almost no COX activity. The
      introduction of a 4-fluorophenyl substituent resulted in retained high COX-2
      affinity, making these compounds together with the feasible one step reaction
      promising candidates for the development of fluorine-18 labelled radiotracers.

PMID- 30108945
TI  - Synthesis and growth-inhibitory activities of imidazo[5,1-d]-1,2,3,5-tetrazine-8
      carboxamides related to the anti-tumour drug temozolomide, with appended silicon,
      benzyl and heteromethyl groups at the 3-position.
AB  - A series of 3-(benzyl-substituted)-imidazo[5,1-d]-1,2,3,5-tetrazines (13) and
      related derivatives with 3-heteromethyl groups has been synthesised and screened
      for growth-inhibitory activity in vitro against two pairs of glioma cell lines
      with temozolomide-sensitive and -resistant phenotypes dependent on the
      absence/presence of the DNA repair protein O6-methylguanine-DNA methyltransferase
      (MGMT). In general the compounds had low inhibitory activity with GI50 values >50
      MUM against both sets of cell lines. Two silicon-containing derivatives, the TMS
      methylimidazotetrazine (9) and the SEM-analogue (10), showed interesting
      differences: compound (9) had a profile very similar to that of temozolomide with
      the MGMT+ cell lines being 5 to 10-fold more resistant than MGMT- isogenic
      partners; the SEM-substituted compound (10) showed potency across all cell lines
      irrespective of their MGMT status.

PMID- 30108943
TI  - Synthesis, characterization and biological evaluation of six highly cytotoxic
      ruthenium(ii) complexes with 4'-substituted-2,2':6',2''-terpyridine.
AB  - Herein, six ruthenium(ii) terpyridine complexes, i.e. [RuCl2(4-EtN-Phtpy)(DMSO)]
      (Ru1), [RuCl2(4-MeO-Phtpy)(DMSO)] (Ru2), [RuCl2(2-MeO-Phtpy)(DMSO)] (Ru3),
      [RuCl2(3-MeO-Phtpy)(DMSO)] (Ru4), [RuCl2(1-Bip-Phtpy)(DMSO)] (Ru5), and [RuCl2(1
      Pyr-Phtpy)(DMSO)] (Ru6) with 4'-(4-diethylaminophenyl)-2,2':6',2''-terpyridine (4
      EtN-Phtpy), 4'-(4-methoxyphenyl)-2,2':6',2''-terpyridine (4-MeO-Phtpy), 4'-(2
      methoxyphenyl)-2,2':6',2''-terpyridine (2-MeO-Phtpy), 4'-(3-methoxyphenyl)
      2,2':6',2''-terpyridine (3-MeO-Phtpy), 4'-(1-biphenylene)-2,2':6',2''-terpyridine
      (1-Bip-Phtpy), and 4'-(1-pyrene)-2,2':6',2''-terpyridine (1-Pyr-Phtpy),
      respectively, were synthesized and fully characterized. The MTT assay
      demonstrates that the in vitro anticancer activity of Ru1 is higher than that of
      Ru2-Ru6 and more selective for Hep-G2 cells than for normal HL-7702 cells. In
      addition, various biological assays show that Ru1 and Ru6, especially the Ru1
      complex, are telomerase inhibitors targeting c-myc G4 DNA and also cause
      apoptosis of Hep-G2 cells. With the same Ru center, the in vitro antitumor
      activity and cellular uptake ability of the 4-EtN-Phtpy and 1-Bip-Phtpy ligands
      follow the order 4-EtN-Phtpy > 1-Bip-Phtpy.

PMID- 30108946
TI  - Membrane activity profiling of small molecule B. subtilis growth inhibitors
      utilizing novel duel-dye fluorescence assay.
AB  - Small molecule disruption of the bacterial membrane is both a challenge and
      interest for drug development. While some avoid membrane activity due to toxicity
      issues, others are interested in leveraging the effects for new treatments.
      Existing assays are available for measuring disruption of membrane potential or
      membrane permeability, two key characteristics of the bacterial membrane, however
      they are limited in their ability to distinguish between these properties. Here,
      we demonstrate a high throughput assay for detection and characterization of
      membrane active compounds. The assay distinguishes the effect of small molecules
      on either the membrane potential or membrane permeability using the fluorescent
      dyes TO-PRO-3 iodide and DiOC2(3) without the need for secondary assays. We then
      applied this assay to a library of 3520 synthetic molecules previously shown to
      inhibit growth of B. subtilis in order to determine the frequency of membrane
      activity within such a biologically active library. From the library, we found
      249 compounds that demonstrated significant membrane activity, suggesting that
      synthetic libraries of this kind do not contain a plurality of membrane active
      molecules.

PMID- 30108947
TI  - Structure-guided approach identifies a novel class of HIV-1 ribonuclease H
      inhibitors: binding mode insights through magnesium complexation and site
      directed mutagenesis studies.
AB  - Persistent HIV infection requires lifelong treatment and among the 2.1 million
      new HIV infections that occur every year there is an increased rate of
      transmitted drug-resistant mutations. This fact requires a constant and timely
      effort in order to identify and develop new HIV inhibitors with innovative
      mechanisms. The HIV-1 reverse transcriptase (RT) associated ribonuclease H (RNase
      H) is the only viral encoded enzyme that still lacks an efficient inhibitor
      despite the fact that it is a well-validated target whose functional abrogation
      compromises viral infectivity. Identification of new drugs is a long and
      expensive process that can be speeded up by in silico methods. In the present
      study, a structure-guided screening is coupled with a similarity-based search on
      the Specs database to identify a new class of HIV-1 RNase H inhibitors. Out of
      the 45 compounds selected for experimental testing, 15 inhibited the RNase H
      function below 100 MUM with three hits exhibiting IC50 values <10 MUM. The most
      active compound, AA, inhibits HIV-1 RNase H with an IC50 of 5.1 MUM and exhibits
      a Mg-independent mode of inhibition. Site-directed mutagenesis studies provide
      valuable insight into the binding mode of newly identified compounds; for
      instance, compound AA involves extensive interactions with a lipophilic pocket
      formed by Ala502, Lys503, and Trp (406, 426 and 535) and polar interactions with
      Arg557 and the highly conserved RNase H primer-grip residue Asn474. The
      structural insights obtained from this work provide the bases for further lead
      optimization.

PMID- 30108950
TI  - Outstanding Reviewers for MedChemComm in 2017.
AB  - We would like to take this opportunity to highlight the Outstanding Reviewers for
      MedChemComm in 2017, as selected by the editorial team for their significant
      contribution to the journal.

PMID- 30108948
TI  - Synthesis and evaluation of nuciferine and roemerine enantiomers as 5-HT2 and
      alpha1 receptor antagonists.
AB  - In this study, the (S)-enantiomers of the aporphine alkaloids, nuciferine and
      roemerine, were prepared via a synthetic route involving catalytic asymmetric
      hydrogenation and both stereoisomers were evaluated in vitro for functional
      activity at human 5-HT2 and adrenergic alpha1 receptor subtypes using a
      transforming growth factor-alpha shedding assay. Both enantiomers of each of the
      compounds were found to act as antagonists at 5-HT2 and alpha1 receptors. (R)
      roemerine was the most potent compound at 5-HT2A and 5-HT2C receptors (pKb = 7.8
      7.9) with good selectivity compared to (S)-roemerine at these two receptors and
      compared to its activity at 5-HT2B, alpha1A, alpha1B and alpha1D receptors.

PMID- 30108949
TI  - Conformationally restricted benzothienoazepine respiratory syncytial virus
      inhibitors: their synthesis, structural analysis and biological activities.
AB  - Atropisomeric drug substances are known to have different biological properties.
      Compounds containing the N-benzoylbenzazepine motif have been shown to exhibit
      energetically restricted rotation around the Ar(CO)N axis. Herein we report, for
      the first time, the synthesis, physical characterisation and anti-viral profiles
      of a series of C-4 and C-5 methylated thieno-benzazepines. NMR analysis reveals
      that incorporation of a single additional substituent at either of these loci
      influences the conformational dynamics of the azepine ring system. In the case of
      the C-5 alkyl analogues, the influence of the new stereocentre is so pronounced
      that its absolute configuration determines which unique atropisomer is obtained
      following the generation of the benzazepine nucleus. Screening of the alkylated
      derivatives for their anti-respiratory syncytial virus (RSV) activity indicates
      that the desired viral pathogenicity is strongly associated with the conformation
      adopted by the modified tricyclic scaffolds. This is particularly evident in the
      case of the C-5 homologues in which one atropisomer was found to be potently
      active and the other essentially inert. These results provide compelling evidence
      that we have determined the bioactive conformation shared by RSV inhibitors that
      employ the thienobenazapine nucleus as their core molecular architecture.
      Furthermore, the understanding obtained from these studies may make it possible
      to design improved agents against RSV infection in the future.

PMID- 30108951
TI  - Approaches to target tractability assessment - a practical perspective.
AB  - The assessment of the suitability of novel targets to intervention by different
      modalities, e.g. small molecules or antibodies, is increasingly seen as important
      in helping to select the most progressable targets at the outset of a drug
      discovery project. This perspective considers differing aspects of tractability
      and how it can be assessed using in silico and experimental approaches. We also
      share some of our experiences in using these approaches.

PMID- 30108953
TI  - Synthesis and radioprotective effects of novel benzyl naphthyl sulfoxide
      (sulfone) derivatives transformed from Ex-RAD.
AB  - In this work, a series of novel benzyl naphthyl sulfoxides (sulfones) derived
      from Ex-RAD were designed and synthesized as potential radioprotective agents.
      Some of the compounds considerably protected HUVECs against 60Co gamma
      irradiation, accompanied by the absence of cytotoxicity. Compared to Ex-RAD,
      compound 8n not only exhibited a significant protective effect on cell survival
      and radiation-induced DNA damage, but also remarkably enhanced the survival
      (100%) of mice in 30 days after being exposed to irradiation. The results
      suggested that some target compounds are valuable for further research as
      promising radioprotectors.

PMID- 30108952
TI  - Revisiting amino acids and peptides as anti-glycation agents.
AB  - The importance of controlling or preventing protein glycation cannot be
      overstated and is of prime importance in the treatment of diabetes and associated
      complications including Alzheimer's disease, cataracts, atherosclerosis, kidney
      aliments among others. In this respect, simple molecules such as amino acids and
      peptides hold much promise both in terms of ease and scale-up of synthesis as
      well as in relation to negligible/low associated toxicity. In view of this, a
      comprehensive account of literature reports is presented, that documents the anti
      glycation activity of natural and non-natural amino acids and peptides. This
      review also discusses the chemical reactions involved in glycation and the
      formation of advanced glycation end-products (AGEs) and possible/probable
      intervention sites and mechanism of action of the reported amino acids/peptides.
      This aspect of amino acids/peptides adds to their growing importance in medicinal
      and therapeutic applications.

PMID- 30108955
TI  - The critical role of novel benzophenone analogs on tumor growth inhibition
      targeting angiogenesis and apoptosis.
AB  - In modern biology, one of the major topics of importance is progress in anti
      cancer drugs with specific targets. The angiopreventive and in vitro tumor
      inhibition activities of novel synthetic benzophenone analogs have been
      investigated intensively and explored in a very systematic way. Novel
      benzophenone analogs (9a-d and 10a-d) substituted with methyl, chloro and fluoro
      groups at different positions on an identical chemical backbone and incorporating
      variations in the number of substituents have been synthesized in a multistep
      process and characterized. In this study, we further evaluate the newly
      synthesized compounds for their cytotoxic and anti-proliferative effects against
      A549, HeLa and MCF-7 cells. The potent lead compound was further assessed for
      anti-angiogenic effects. Through the structure-activity relationship, we found
      that an increase in the number of methyl, chloro and fluoro groups in a
      benzophenone ring on compound 9d resulted in higher potency compared to other
      compounds. Tumor inhibition was notably promoted, and this was reflected in
      effects on neovessel formation in in vivo systems, such as the CAM. Compound 9d
      interacts with rVEGF through hydrogen bonds in silico, thereby down-regulating
      the expression of VEGF in angiogenesis. From our investigation, it is suggested
      on the basis of clonogenesis and cell migration assays that compound 9d has the
      potency to exhibit prolonged activity against cancer progression, through cell
      cycle arrest at the G2/M phase. In addition, compound 9d inhibits A549 cells
      through caspase-activated DNase-mediated apoptosis.

PMID- 30108954
TI  - Anti-cancer effect of a novel 2,3-didithiocarbamate-substituted naphthoquinone as
      a tumor metabolic suppressor in vitro and in vivo.
AB  - Tumor cells reprogram their cellular metabolism by switching from oxidative
      phosphorylation to aerobic glycolysis to support aberrant cell proliferation.
      Suppressing tumor cell metabolism has become an attractive strategy for treating
      cancer patients. In this study, we identified a 2,3-didithiocarbamate-substituted
      naphthoquinone 3i that inhibited the proliferation of tumor cells by disturbing
      their metabolism. Compound 3i reduced cancer cell viability with IC50 values from
      50 nM to 150 nM against HCT116, MCF7, MDA-MB231, HeLa, H1299 and B16 cells.
      Further, compound 3i was found to suppress ATP production in cultured cancer
      cells, inhibit the M2 isoform of pyruvate kinase (PKM2) which is a rate-limiting
      enzyme in the glycolytic pathway and block the subsequent transcription of the
      downstream genes GLUT1, LDH and CCND1. In addition, exposure to compound 3i
      significantly suppressed tumor growth in a B16 melanoma transplantation mouse
      model and a spontaneous breast carcinoma mouse model in vivo. The identification
      of compound 3i as a tumor metabolic suppressor not only offers a candidate
      compound for cancer therapy, but also provides a tool for an in-depth study of
      tumor metabolism.

PMID- 30108956
TI  - Studies towards elucidating the potential of 5,10,15,20-tetrakis(p-carboxy
      methyleneoxyphenyl)porphyrin as a theranostic agent for applications in PET and
      PDT.
AB  - Porphyrins, owing to their inherent tendency to accumulate in tumorous lesions,
      are considered suitable for developing agents for theranostic applications
      involving tumor diagnosis and targeted tumor therapy. The aim of the present work
      is to study the potential of a porphyrin derivative namely, 5,10,15,20-tetrakis(p
      carboxymethyleneoxyphenyl)porphyrin (SPTA) as a theranostic agent for
      applications in positron emission tomography (PET) and photodynamic therapy
      (PDT). SPTA was synthesized in-house following a three-step reaction process and
      characterized by using spectroscopic techniques, viz. UV-vis, FT-IR, 1H-NMR and
      13C-NMR spectroscopy, as well as by mass spectrometry. SPTA was labeled with
      68Ga, a generator produced PET radioisotope, and the radiolabeled product was
      characterized by HPLC. The 68Ga-SPTA complex was prepared with a radiochemical
      purity of >95% under optimized conditions. The diagnostic potential of 68Ga-SPTA
      was evaluated by cell uptake studies in two different tumor cell lines (HT1080
      and A549) which revealed the affinity of 68Ga-SPTA towards the cancer cells.
      Biodistribution studies carried out in Swiss mice bearing fibrosarcoma tumors
      exhibited the accumulation of the radiotracer in the tumor. The therapeutic
      potential of SPTA was evaluated by determining its photo-cytotoxicity employing
      the MTT assay in HT1080 and A549 cell lines using three different light doses,
      which indicated the significant cytotoxicity of SPTA in the presence of light.
      The present study indicates the possible potential of SPTA in radionuclide
      imaging as well as in photodynamic therapy (PDT) thus confirming the promising
      theranostic nature of this porphyrin derivative.

PMID- 30108957
TI  - Crystallomycin revisited after 60 years: aspartocins B and C.
AB  - The study of an archived sample of crystallomycin complex using HPLC, ESI HRMS,
      and 2D NMR showed that two major components of the antibiotic, compounds 1 and 2,
      are lipopeptides having the same peptide core, Asp1-cyclo(Dab2-Pip3-MeAsp4-Asp5
      Gly6-Asp7-Gly8-Dab9-Val10-Pro11-), N-acylated either with Delta3-iso
      tetradecenoyl or Delta3-anteiso-pentadecenoyl that are identical to aspartocins C
      and B, respectively. According to the 2D NMR study, compound 2 in DMSO solution
      exists as a mixture of four conformers. The producing strain was identified as
      Streptomyces griseorubens. Compounds 1 and 2 have considerable Ca2+-dependent
      activity against Gram-positive bacteria including five MRSA strains.

PMID- 30108958
TI  - Discovery of 2-aminoimidazole and 2-amino imidazolyl-thiazoles as non-xanthine
      human adenosine A3 receptor antagonists: SAR and molecular modeling studies.
AB  - A small-molecule combinatorial library of 24 compounds with 2-aminoimidazole and
      2-aminoimidazolyl-thiazole derivatives was synthesized using a 2-chloro trityl
      resin. The generated compound library was tested against all the human adenosine
      receptors subtypes. The 2-aminoimidazole derivatives (6a-6l) showed weak to
      moderate affinity towards the human adenosine receptors. Further modification to
      2-aminoimidazolyl-thiazole derivatives (12a-12l) resulted in an improvement of
      affinity at adenosine A1, A2A and A3 receptor subtypes. Compound 12b was the most
      potent and selective non-xanthine human adenosine A3 receptor antagonist of this
      series. A receptor-based modeling study was performed to explore the possible
      binding mode of these novel 2-aminoimidazole and 2-aminoimidazolyl-thiazole
      derivatives into human adenosine A1, A2A and A3 receptor subtypes.

PMID- 30108959
TI  - Design, synthesis and antimycobacterial activity of hybrid molecules combining
      pyrazinamide with a 4-phenylthiazol-2-amine scaffold.
AB  - Hybrid compounds based on a combination of the first-line antitubercular
      pyrazinamide (PZA) and a formerly identified antimycobacterial scaffold of 4
      arylthiazol-2-amine were designed. Eighteen compounds were prepared,
      characterized and tested for in vitro growth inhibition activity against M.
      tuberculosis H37Rv, M. kansasii, M. avium and M. smegmatis by Microplate Alamar
      Blue Assay at neutral pH. Active compounds were tested for in vitro cytotoxicity
      in the human hepatocellular carcinoma cell line (HepG2). The most active 6-chloro
      N-[4-(4-fluorophenyl)thiazol-2-yl]pyrazine-2-carboxamide (9b) also had the
      broadest spectrum of activity and inhibited M. tuberculosis, M. kansasii, and M.
      avium with MIC = 0.78 MUg mL-1 (2.3 MUM) and a selectivity index related to HepG2
      cells of SI > 20. Structure-activity relationships within the series are
      discussed. Based on its structural similarity to known inhibitors and the results
      of a molecular docking study, we suggest mycobacterial beta-ketoacyl-(acyl
      carrier-protein) synthase III (FabH) as a potential target.

PMID- 30108961
TI  - Novel 99mTc-labelled complexes with thymidine isocyanide: radiosynthesis and
      evaluation as potential tumor imaging tracers.
AB  - A novel thymidine isocyanide (CN-TdR) functionalized at the N3 position of
      thymidine was synthesized and then radiolabelled with 99mTc(i) and
      [99mTc(i)(CO)3]+ cores to produce [99mTc(CN-TdR)6]+ and [99mTc(CO)3(CN-TdR)3]+,
      respectively. Both of them were prepared with high radiochemical purity and were
      stable over 6 h in saline at ambient temperature and in serum at 37  degrees C.
      The partition coefficient results demonstrated that they were hydrophilic. The
      cell internalization studies showed that their uptake might be mediated by
      nucleoside transporters. Biodistribution of these complexes in mice bearing the
      S180 tumor showed that they accumulated in the tumor with high uptake and cleared
      rapidly from blood and muscles, producing high tumor/blood and tumor/muscle
      ratios. Between them, [99mTc(CN-TdR)6]+ exhibited advantages concerning a higher
      tumor uptake, tumor/blood ratio and tumor/muscle ratio at 60 min post-injection.
      Single photon emission computed tomography imaging studies showed that there was
      a clear accumulation in tumor sites, suggesting that [99mTc(CN-TdR)6]+ could be a
      promising candidate for tumor imaging.

PMID- 30108962
TI  - Development of piperazine-1-carbothioamide chitosan silver nanoparticles (P1C
      Tit*CAgNPs) as a promising anti-inflammatory candidate: a molecular docking
      validation.
AB  - Natural products are important leads in drug discovery. The search for effective
      plant-derived agents or their synthetic analogues has continued to be of interest
      to biologists and chemists for a long time. Herein, we have synthesized a novel
      compound, P1C, and P1C-Tit*CAgNPs from chitosan; P1C is a precursor and an anti
      inflammatory candidate, which has been validated by molecular docking studies.
      The synthesized P1C-Tit*CAgNPs showed monodisperse, spherical, and cationic
      nature and antioxidant properties, protecting destabilization of the erythrocyte
      membrane by the azo compound 2,2'-azobis(2-amidinopropane)dihydrochloride (AAPH);
      the involvement of NPs as a protective agent for biomolecules, such as DNA and
      protein, followed by the treatment of NPs with AAPH was confirmed. The inhibition
      of cellular damage and leakage of cellular inflammatory agents was confirmed by
      AFM, SEM, TEM, SDS-PAGE, LDH, and PLA2 enzyme inhibition via in vitro studies.
      The anti-inflammatory property of P1C was further validated by in silico
      molecular docking studies and showed that, the P1C best pose aligned to PLA2
      compared to standard drug. The significant anticancer property of P1C-Tit*CAgNPs
      was confirmed against MCF7, U373, and C6 cancer cell lines. Thus, the present
      study highlights the synthesized P1C in P1C-Tit*CAgNPs as a target PLA2-specific
      anti-inflammatory candidate, and further tuning of small and development
      functionalized nanoparticles has a great future in medicine; hence, their
      clinical applications are warranted.

PMID- 30108960
TI  - Discovery and biological evaluation of N5-substituted 6,7-dioxo-6,7
      dihydropteridine derivatives as potent Bruton's tyrosine kinase inhibitors.
AB  - Bruton's tyrosine kinase (BTK) plays a critical role in B cell receptor (BCR)
      mediated signaling pathways responsible for the development and function of B
      cells, which makes it an attractive target for the treatment of many types of B
      cell malignancies. Herein, a series of N5-substituted 6,7-dioxo-6,7
      dihydropteridine-based, irreversible BTK inhibitors were reported with IC50
      values ranging from 1.9 to 236.6 nM in the enzymatic inhibition assay. Compounds
      6 and 7 significantly inhibited the proliferation of Ramos cells which
      overexpress the BTK enzyme, as well as the autophosphorylation of BTK at Tyr223
      and the activation of its downstream signaling molecule PLCgamma2. Overall, this
      series of compounds could provide a promising starting point for further
      development of potent BTK inhibitors for B-cell malignancy treatment.

PMID- 30108963
TI  - Saponin from sea cucumber exhibited more significant effects than ginsenoside on
      ameliorating high fat diet-induced obesity in C57BL/6 mice.
AB  - Obesity and its comorbidities are considered to be a severe public health
      problem. Many natural compounds found in food have been proved to ameliorate the
      metabolic abnormalities induced by obesity. The purpose of this study was to
      compare the effects of saponin from sea cucumber (SSC) and ginsenoside (SG) on
      improving the lipid metabolism in C57BL/6 mice fed with a high fat diet. The mice
      were randomly divided into six groups including a low fat diet group (LF), a high
      fat diet group (HF), and four dietary intervention groups. The administration of
      SSC for 8 weeks exhibited a more significant reduction in HF induced fat mass,
      weight gain, lipid levels in the liver and serum, and serum glucose and insulin
      levels than SG. Further research indicated that SSC ameliorated high fat diet
      induced obesity in C57BL/6 mice mainly through inhibiting lipid synthesis and
      accelerating lipid beta-oxidation and glycolysis in the liver. These results
      suggested that saponin from sea cucumber might be applied as a food supplement
      and/or functional ingredient to relieve metabolic disorders induced by obesity.

PMID- 30108964
TI  - Effect of isouronium/guanidinium substitution on the efficacy of a series of
      novel anti-cancer agents.
AB  - Considering our hypothesis that the guanidinium moiety in the protein kinase type
      III inhibitor 1 interacts with a phosphate of ATP within the hinge region, the
      nature of the interactions established between a model isouronium and the
      phosphate groups of ATP was computationally analysed indicating that an
      isouronium derivative of 1 will interact in a similar manner with ATP. Thus, a
      number of compounds were prepared to assess the effect of the
      guanidinium/isouronium substitution on cancer cell growth; additionally, the
      molecular shortening and conformational change induced by replacing the di
      substituted guanidine-linker of 1 by an amide was explored. The effect of these
      compounds on cell viability was tested in human leukaemia, breast cancer and
      cervical cancer cell lines and the resulting IC50 values were compared with those
      of the lead compound 1. Replacement of the di-substituted guanidine-linker by an
      amide results in the loss of cytotoxicity; however, substitution of the mono
      substituted guanidinium by an isouronium cation seems to be beneficial for cell
      growth inhibition. Additionally, the effect of these compounds on the MAPK/ERK
      pathway was studied by means of Western blotting and the results indicate that
      the isouronium derivative 2 decreases the levels of phosphorylated, and thus
      activated, ERK (pERK) both in leukaemia and breast cancer cells, whereas lead
      compound 1 only shows an effect on pERK levels in breast cancer cells. This
      confirms that both compounds could interfere with the MAPK/ERK pathway although
      other targets cannot be ruled out.

PMID- 30108965
TI  - What are the drugs of the future?
AB  - Are small molecules or biologics the drugs of the future? Small-molecule drugs
      have historically been the pillars of traditional medicine. However, recently, we
      seem to be amidst a scientific revolution with the rise of many FDA-approved
      biologic drugs. This opinion article looks at the current state of small
      molecules and biologics and assesses what the future holds for these two broad
      classes of drugs.

PMID- 30108967
TI  - A peptide inhibitor of antibody-dependent cell-mediated cytotoxicity against
      EGFR/folate receptor-alpha double positive cells.
AB  - Antibody-dependent cell-mediated cytotoxicity (ADCC) is caused by natural killer
      (NK) cells upon recognition of antigen-bound IgG via FcgammaRIIIa. This mechanism
      is crucial for cytolysis of pathogen-infected cells and monoclonal antibody (mAb)
      mediated elimination of cancer cells. However, there is concern that mAb-based
      cancer therapy induces ADCC against non-target cells expressing antigens. To
      date, no strategy has been reported to enhance the selectivity of ADCC to protect
      non-target cells expressing antigens. Here, we introduce a model inhibitor which
      specifically blocks ADCC of anti-EGFR mAbs towards EGFR/folate receptor alpha
      (FRalpha) double positive cells. This inhibitor recruits mAbs on the FRalpha of
      the cell surface independent of Fab antigen recognition. The resulting ternary
      and/or quaternary complexes formed on the cell surface suppress signal
      transduction of FcgammaRIIIa in NK cells, consequently leading to more specific
      ADCC.

PMID- 30108966
TI  - Schizophrenia: synthetic strategies and recent advances in drug design.
AB  - Schizophrenia is a complex and unpredictable mental disorder which affects
      several domains of cognition and behaviour. It is a heterogeneous illness
      characterised by positive, negative, and cognitive symptoms, often accompanied by
      signs of depression. In this tutorial review, we discuss recent progress in
      understanding the target sites and mechanisms of action of second-generation
      antipsychotic drugs. Progress in identifying and defining target sites has been
      accelerated recently by advances in neuroscience, and newly developed agents that
      regulate signalling by the main excitatory neurotransmitters in the brain are
      surveyed. Examples of novel molecules for the treatment of schizophrenia in
      preclinical and clinical development and their industrial sponsors are
      highlighted.

PMID- 30108968
TI  - The semi-synthesis, biological evaluation and docking analysis of the oxime,
      hydrazine and hydrazide derivatives of platensimycin.
AB  - A dozen oxime, hydrazine and hydrazide derivatives of platensimycin (PTM)
      analogues were synthesized, some of which showed strong antibacterial activities
      and were shown to be stable under the bioassay conditions. Docking analysis
      revealed that they have certain new interactions with beta-ketoacyl-[acyl carrier
      protein] synthase II (FabF), suggesting that Schiff base formation on its terpene
      scaffold is an effective strategy to diversify PTM structure.

PMID- 30108969
TI  - Design, synthesis and biological evaluation of novel 1,3-diarylpyrazoles as
      cyclooxygenase inhibitors, antiplatelet and anticancer agents.
AB  - With the aim of achieving new compounds possessing both anti-inflammatory and
      antiplatelet activities, we synthesized (E)-3-[3-(pyridin-3/4-yl)-1
      (phenyl/sulfonylmethylphenyl)-1H-pyrazol-4-yl]acrylamides, and evaluated their
      COX-1 and COX-2 inhibitory and antiplatelet activities. Since COX-2 inhibitory
      and antiplatelet compounds have anticancer potential, we also screened their
      antiproliferative effects against three human cancer cell lines. Compounds 5n,
      5p, 5s, 10d, 10g and 10i were determined as dual COX-2 inhibitor/antiplatelet
      compounds. Compound 10h appeared to be a compound that exhibited antiplatelet
      activity without inhibiting the COX enzyme. Compounds 5h, 10a and 10i were the
      most effective derivatives which displayed antiproliferative activity against
      Huh7, MCF7 and HCT116 cells. Particularly, compound 10i, as the compound
      exhibiting the highest cytotoxic, antiplatelet and COX-2 inhibitory activity, was
      remarkable.

PMID- 30108970
TI  - Development of a peptide-based bifunctional chelator conjugated to a cytotoxic
      drug for the treatment of melanotic melanoma.
AB  - The cytotoxic drug gemcitabine (GEM) has been conjugated to receptor-binding
      peptides to target melanoma tumors. A hexapeptide having a Lys-Gly-His-Lys
      sequence (pep-1), an octapeptide with an Arg-Gly-Asp-Lys-Gly-His-Lys sequence
      (pep-2), a GEM-conjugated Lys-Gly-His-Lys peptide (GEM-pep-3) and a GEM
      conjugated Asp-Gly-Arg peptide (GEM-pep-4) were synthesized and characterized. In
      vitro uptake of fluorescently labeled GEM-pep-3 and GEM-pep-4 on B16F10 cells was
      investigated. Fluorescence microscopy studies demonstrated significant uptake of
      GEM-pep-3 in the B16F10 mouse melanoma cell line. The peptides and GEM-coupled
      peptides were radiolabeled with [99mTc(CO)3(H2O)3]+ and examined for in vitro
      cell binding in the B16F10 melanoma cell line and in vivo biodistribution and
      scintigraphic studies in a B16F10 melanoma tumor-bearing mice model. In vitro
      cellular uptake studies and biological evaluation confirmed significant
      deposition of GEM-pep-3 at the melanoma tumor site. The MTT assay depicted higher
      cytotoxic behaviour of GEM-pep-3 than free GEM. A considerable amount of cell
      apoptosis was also observed in B16F10 cells. Finally, the in vivo therapeutic
      efficacy study revealed a significant decrease in tumor growth in the GEM-pep-3
      treated animal model. These studies reveal enough potentiality of GEM-pep-3 to
      treat melanoma and underline the need for further evaluation.

PMID- 30108971
TI  - Reduction-rebridging strategy for the preparation of ADPN-based antibody-drug
      conjugates.
AB  - The reduction-rebridging strategy is a powerful method for the preparation of
      stable and homogeneous antibody-drug conjugates (ADCs). In this communication, we
      describe the development of the arylene-dipropiolonitrile (ADPN) functional group
      for the rebridging of reduced disulphide bonds and its application in the
      preparation of potent and selective ADCs.

PMID- 30108973
TI  - Synthesis and biological evaluation of new 3-amino-2-azetidinone derivatives as
      anti-colorectal cancer agents.
AB  - Several synthetic combretastatin A4 (CA-4) derivatives were recently prepared to
      increase the drug efficacy and stability of the natural product isolated from the
      South African tree Combretum caffrum. A group of ten 3-amino-2-azetidinone
      derivatives, as combretastatin A4 analogues, was selected through docking
      experiments, synthesized and tested for their anti-proliferative activity against
      the colon cancer SW48 cell line. These molecules, through the formation of amide
      bonds in position 3, allow the synthesis of various derivatives that can modulate
      the activity with great resistance to hydrolytic conditions. The cyclization to
      obtain the 3-aminoazetidinone ring is highly diastereoselective and provides a
      trans biologically active isomer under mild reaction conditions with better
      yields than the 3-hydroxy-2-azetidinone synthesis. All compounds showed IC50
      values ranging between 14.0 and 564.2 nM, and the most active compound showed
      inhibitory activity against tubulin polymerization in vitro, being a potential
      therapeutic agent against colon cancer.

PMID- 30108972
TI  - Synthesis, characterization and biological evaluation of Pd(ii), Cu(ii), Re(i)
      and 99mTc(i) thiazole-based complexes.
AB  - A new thiazole-containing multidentate ligand 2-((2-phenylthiazol-4
      yl)methylthio)ethanamine, L, was synthesized and used to prepare new complexes of
      the formula PdIILCl2 (Pd-L), CuIIL2Cl2 (Cu-L) and fac-[Re/99mTcI(CO)3(L)]+
      (Re/99mTc-L). The ligand L and the metal complexes were characterized
      spectroscopically. Furthermore, the structures of Re-L and Cu-L were elucidated
      by X-ray crystallography. Ligand L acts as a bidentate (Nth, S) chelator in Pd-L,
      as a bidentate (N, S) chelator in Cu-L and as a tridentate (Nth, S, N) chelator
      in Re-L. The radiotracer 99mTc-L was synthesized in high yield and characterised
      by HPLC comparison with the Re-L analog. The synthesized compounds were evaluated
      for their anti-inflammatory and cytotoxic properties. The compounds exhibited low
      anti-inflammatory activity with Pd-L showing the highest activity among them. The
      cytotoxic activity of the ligand and the complexes against several human cancer
      cell lines (cervical adenocarcinoma HeLa, colorectal adenocarcinoma LS-174T, lung
      adenocarcinoma A549, breast adenocarcinoma MDA-MB-231 and normal human lung
      fibroblast cell line MRC-5) was examined using the MTT assay. The complex Cu-L
      exhibited the highest cytotoxicity and the complex Pd-L showed the best tumor
      selectivity. The changes in the cell cycle phase distribution were determined by
      flow cytometry and it was found that ligand L shows the highest apoptotic
      activity. The biodistribution studies of 99mTc-L in mice showed fast tissue
      clearance. Of all the thiazole-containing compounds, the palladium complex
      appears to be more promising for future efforts.

PMID- 30108974
TI  - Design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom
      tyrosinase inhibitors.
AB  - Tyrosinase is a key enzyme in melanin biosynthesis, and is also involved in the
      enzymatic browning of plant-derived foods. Tyrosinase inhibitors are very
      important in medicine, cosmetics and agriculture. In order to develop more active
      and safer tyrosinase inhibitors, an efficient approach is to modify natural
      product scaffolds. In this work, two series of novel tyrosinase inhibitors were
      designed and synthesized by the esterification of cinnamic acid derivatives with
      paeonol or thymol. Their inhibitory effects on mushroom tyrosinase were
      evaluated. Most of these compounds (IC50: 2.0 to 163.8 MUM) are found to be
      better inhibitors than their parent compounds (IC50: 121.4 to 5925.0 MUM). Among
      them, (E)-2-acetyl-5-methoxyphenyl-3-(4-hydroxyphenyl)acrylate (5a), (E)-2-acetyl
      5-methoxyphenyl-3-(4-methoxyphenyl)acrylate (5g) and (E)-2-isopropyl-5
      methylphenyl-3-(4-hydroxyphenyl)acrylate (6a) showed strong inhibitory
      activities; the IC50 values were 2.0 MUM, 8.3 MUM and 10.6 MUM, respectively,
      compared to the positive control, kojic acid (IC50: 32.2 MUM). Analysis of the
      inhibition mechanism of 5a, 5g and 6a demonstrated that their inhibitory effects
      on tyrosinase are reversible. The inhibition kinetics, analyzed by Lineweaver
      Burk plots, revealed that 5a acts as a non-competitive inhibitor while 5g and 6a
      are mixed-type inhibitors. Furthermore, docking experiments were carried out to
      study the interactions between 6a and mushroom tyrosinase.

PMID- 30108975
TI  - New tetrahydroisoquinoline-based P-glycoprotein modulators: decoration of the
      biphenyl core gives selective ligands.
AB  - P-glycoprotein (P-gp, MDR1) is a membrane transporter expressed in several
      regions of our body. It plays a crucial defense role as it mediates the efflux of
      hundreds of potentially toxic substances. However, P-gp is one of the main causes
      of failure in cancer chemotherapy, as a number of chemotherapeutic agents are P
      gp substrates. Another interesting implication concerns the correlation between P
      gp expression impairment and the onset of several central nervous system
      pathologies such as Alzheimer's and Parkinson's diseases. In view of these
      considerations, in the present study, a new series of P-gp modulators have been
      designed, synthesized and evaluated for their activity towards P-gp and two other
      sister proteins (BCRP and MRP1). The compounds, structurally correlated to the
      potent but non-selective P-gp inhibitor MC70 [4'-(6,7-dimethoxy-3,4-dihydro-1H
      isoquinolin-2-ylmethyl)biphenyl-4-ol], proved fairly selective towards P-gp, with
      a potency in the micromolar range. Compounds 5a, 5d and 12d proved capable of
      restoring doxorubicin toxicity in resistant cancer cells.

PMID- 30108976
TI  - Design, synthesis and antimicrobial activity of usnic acid derivatives.
AB  - Usnic acid, a dibenzofuran, was originally isolated from lichens producing
      secondary metabolites, and is well known as an antibiotic, but is also endowed
      with several other interesting properties. Thus, the goal of this paper is the
      design of new usnic acid derivatives and evaluation of their antimicrobial
      activity. All newly synthesized compounds possess good antibacterial activity
      with MIC ranging from 1.02-50.93 * 10-2 mmol mL-1 and MBC from 2.05-70.57 * 10-2
      mmol mL-1. The most sensitive bacterial species was Staphylococcus aureus, while
      Pseudomonas aeruginosa and Escherichia coli were the most resistant among the
      ATCC strains, and MRSA was the most resistant among all tested bacteria (ATCC and
      clinical isolates). Their antifungal activity was very strong (MIC = 0.35-7.53 *
      10-2 mmol mL-1 and MFC = 0.70-15.05 * 10-2 mmol mL-1) - better than those of
      reference compounds and usnic acid itself. The most sensitive fungal species was
      Trichoderma viride, while Penicillium versicolor var. cyclopium appeared to be
      the most resistant. It should be mentioned that in general most of the compounds
      showed weaker antibacterial activity, but better antifungal properties than usnic
      acid itself. The results allow us to conclude that the title compounds are good
      lead compounds for novel more active antibacterial drugs. On the other hand,
      these compounds are very promising as antifungals.

PMID- 30108977
TI  - Inhibition of O-GlcNAc transferase (OGT) by peptidic hybrids.
AB  - O-GlcNAc transferase (OGT) attaches a GlcNAc moiety on specific substrate
      proteins using UDP-GlcNAc as the sugar donor. This modification can alter protein
      function by regulating cellular signaling and transcription pathways in response
      to altered nutrient availability and stress. Specific inhibitors of OGT would be
      valuable tools for biological studies and lead structures for therapeutics. The
      existing OGT inhibitors are mainly derived from the sugar donor substrate, but
      poor cell permeability and off-target effects limit their use. Here, we describe
      our progress on OGT inhibition based on substrate peptides identified by array
      screening. Subsequently, bisubstrate inhibitors were prepared by conjugating
      these peptides to uridine in various ways. In parallel, an in silico fragment
      screening was conducted to obtain small molecules targeting the UDP binding
      pocket. After evaluation of the initial hits, one of these small molecules was
      elaborated into a novel OGT hybrid inhibitor, as the replacement of uridine. The
      novel compounds inhibit OGT activity with IC50 values in the micromolar range.

PMID- 30108978
TI  - Isolation, expression and biochemical characterization of recombinant hyoscyamine
      6beta-hydroxylase from Brugmansia sanguinea - tuning the scopolamine production.
AB  - Hyoscyamine-6beta-hydroxylase (H6H, EC 1.14.11.11) is a plant enzyme that
      catalyses the last two steps in the biosynthesis of the anticholinergic drug
      scopolamine, i.e. the hydroxylation of hyoscyamine to 6beta-hydroxyhyoscyamine
      (anisodamine) and subsequent oxidative ring-closure to the 6,7-beta-epoxide. A
      H6H gene homologue was isolated from the plant Brugmansia sanguinea (BsH6H) and
      recombinantly cloned into Escherichia coli, expressed and purified using an
      effective SUMO-fusion procedure. Enzymatic activity is approximately 40-fold
      higher for the first reaction step and the substrate affinity is comparable to
      other characterized H6H homologues (Km ~ 60 MUM). Truncation of an H6H enzyme
      flexible N-terminal region yields an active and stable yet more compact enzyme
      version.

PMID- 30108979
TI  - Elucidation of fluorine's impact on pKa and in vitro Pgp-mediated efflux for a
      series of PDE9 inhibitors.
AB  - P-Glycoprotein (Pgp)-mediated cellular efflux is recognized as a common challenge
      in CNS drug discovery. In this study, the influence of replacing a hydrogen atom
      with fluorine on the pKa and Pgp-mediated efflux is elucidated for a series of
      PDE9 inhibitors. The PDE9 inhibitors with and without fluorine were synthesized
      using a novel condensation-oxidation approach, providing access to several
      analogues, all from the same stereoenriched aldehyde building block. The
      incorporation of fluorine was found to influence two acid-base functionalities
      concomitantly, both of which were involved in Pgp-recognition. By methylating the
      acidic functionality, it was possible to isolate the effect responsible for
      lowering the Pgp-mediated efflux.

PMID- 30108980
TI  - Antifungal amphiphilic kanamycins: new life for an old drug.
AB  - Classical aminoglycoside antibiotics are obsolete or hampered by the emergence of
      drug resistant bacteria. Recent discoveries of antifungal amphiphilic kanamycins
      offer new strategies for reviving and repurposing these old drugs. A simple
      structural modification turns the clinically obsolete antibacterial kanamycin
      into an antifungal agent. Structure-activity relationship studies have led to the
      production of K20, an antifungal kanamycin that can be mass-produced for uses in
      agriculture as well as in animals. This review delineates the path to the
      discovery of K20 and other related antifungal amphiphilic kanamycins,
      determination of its mode of action, and findings in greenhouse and field trials
      with K20 that could lead to crop disease protection strategies.

PMID- 30108983
TI  - Live-cell fluorescence imaging: assessment of thioflavin T uptake in human
      epidermal carcinoma cells.
AB  - Thioflavin T (ThT), a positively charged heterocyclic small molecule, is a widely
      used fluorescent marker of amyloid pathophysiology to confirm the cause of death
      in post mortem brain tissue of Alzheimer's disease (AD) patients. Literature
      precedents indicate that current positron emission tomography (PET) agents, such
      as 11C-PIB and 18F-flutemetamol, share significant structural similarity with
      ThT, a lipophilic dye which does not traverse the blood-brain barrier (BBB) to
      enable the detection of Abeta plaques in vivo. While vital for maintaining normal
      physiology and healthy brain function, the BBB comprises brain endothelial cells
      sealed via paracellular protein complexes, bound by an extracellular matrix
      forming tight junctions thus controlling the delivery of molecules into the
      brain. The human P-glycoprotein (Pgp/ABCB1, 170 kD plasma membrane protein),
      belonging to the ABC family of efflux transporter proteins, also lines the
      luminal surface of brain endothelial cells thus poised to secrete its recognized
      substrates into the blood. Herein, we postulate that thioflavin T (ThT), due to
      its physico-chemical attributes, such as moderate lipophilicity and protonated
      nitrogen, could very well be recognized as a transport substrate of Pgp (P
      glycoprotein, ABCB1) thus restricting its permeation into the brain. To evaluate
      whether or not ThT is indeed recognized by Pgp as its transport substrate thus
      limiting its BBB permeability, herein, we evaluate cellular accumulation profiles
      of ThT and PiB (a similar structural uncharged mimetic) in human epidermal
      carcinoma KB-3-1 (Pgp-) and MDR KB-8-5 (Pgp+) cells, using live-cell fluorescence
      imaging. While ThT penetrates KB-3-1 cells, it gets excluded from KB-8-5 cells,
      and also indicates LY335979-induced uptake in Pgp-expressing cells. Furthermore,
      the cellular uptake profiles of PiB are not impacted by the expression of Pgp
      under identical conditions. These data show that uptake profiles of ThT have been
      modified by the expression of Pgp in these cells, and are inversely proportional
      to the expression of the transporter protein located on the plasma membrane of
      these cells. Combined data demonstrate that ThT is efficiently recognized by Pgp
      as its transport substrate.

PMID- 30108982
TI  - Discovery of indoleamine 2,3-dioxygenase inhibitors using machine learning based
      virtual screening.
AB  - Indoleamine 2,3-dioxygenase (IDO), an immune checkpoint, is a promising target
      for cancer immunotherapy. However, current IDO inhibitors are not approved for
      clinical use yet; therefore, new IDO inhibitors are still demanded. To identify
      new IDO inhibitors, we have built naive Bayesian (NB) and recursive partitioning
      (RP) models from a library of known IDO inhibitors derived from recent
      publications. Thirteen molecular fingerprints were used as descriptors for the
      models to predict IDO inhibitors. An in-house compound library was virtually
      screened using the best machine learning model, which resulted in 50 hits for
      further enzyme-based IDO inhibitory assays. Consequently, we identified three new
      IDO inhibitors with IC50 values of 1.30, 4.10, and 4.68 MUM. These active
      compounds also showed IDO inhibitory activities in cell-based assays. The
      compounds belong to the tanshinone family, a typical scaffold family derived from
      Danshen (a Chinese herb), the dried root of Salvia miltiorrhiza, which has been
      widely used in China, Japan, the United States, and other European countries for
      the treatment of cardiovascular and cerebrovascular diseases. Thus, we discovered
      a new use for Danshen using machine learning methods. Surface plasmon resonance
      (SPR) experiments proved that the inhibitors interacted with the IDO target.
      Molecular dynamic simulations demonstrated the binding modes of the IDO
      inhibitors.

PMID- 30108981
TI  - An overview of recent molecular dynamics applications as medicinal chemistry
      tools for the undruggable site challenge.
AB  - Molecular dynamics (MD) has become increasingly popular due to the development of
      hardware and software solutions and the improvement in algorithms, which allowed
      researchers to scale up calculations in order to speed them up. MD simulations
      are usually used to address protein folding issues or protein-ligand complex
      stability through energy profile analysis over time. In recent years, the
      development of new tools able to deeply explore a potential energy surface (PES)
      has allowed researchers to focus on the dynamic nature of the binding recognition
      process and binding-induced protein conformational changes. Moreover, modern
      approaches have been demonstrated to be effective and reliable in calculating
      some kinetic and thermodynamic parameters behind the host-guest recognition
      process. Starting from all of these considerations, several efforts have been
      made in order to integrate MD within the virtual screening process in drug
      discovery. Knowledge retrieved from MD can, in fact, be exploited as a starting
      point to build pharmacophores or docking constraints in the early stage of the
      screening campaign as well as to define key features, in order to unravel hidden
      binding modes and help the optimisation of the molecular structure of a lead
      compound. Based on these outcomes, researchers are nowadays using MD as an
      invaluable tool to discover and target previously considered undruggable binding
      sites, including protein-protein interactions and allosteric sites on a protein
      surface. As a matter of fact, the use of MD has been recognised as vital to the
      discovery of selective protein-protein interaction modulators. The use of a
      dynamic overview on how the host-guest recognition occurs and of the relative
      conformational modifications induced allows researchers to optimise small
      molecules and small peptides capable of tightly interacting within the cleft
      between two proteins. In this review, we aim to present the most recent
      applications of MD as an integrated tool to be used in the rational design of
      small molecules or small peptides able to modulate undruggable targets, such as
      allosteric sites and protein-protein interactions.

PMID- 30108985
TI  - N-Acetyl-3-aminopyrazoles block the non-canonical NF-kB cascade by selectively
      inhibiting NIK.
AB  - NF-kappaB-inducing kinase (NIK), an oncogenic drug target that is associated with
      various cancers, is a central signalling component of the non-canonical pathway.
      A blind screening process, which established that amino pyrazole related
      scaffolds have an effect on IKKbeta, led to a hit-to-lead optimization process
      that identified the aminopyrazole 3a as a low MUM selective NIK inhibitor.
      Compound 3a effectively inhibited the NIK-dependent activation of the NF-kappaB
      pathway in tumour cells, confirming its selective inhibitory profile.

PMID- 30108984
TI  - Tricyclic xanthine derivatives containing a basic substituent: adenosine receptor
      affinity and drug-related properties.
AB  - A library of 27 novel amide derivatives of annelated xanthines was designed and
      synthesized. The new compounds represent 1,3-dipropyl- and 1,3-dibutyl
      pyrimido[2,1-f]purinedione-9-ethylphenoxy derivatives including a CH2CONH linker
      between the (CH2)2-amino group and the phenoxy moiety. A synthetic strategy to
      obtain the final products was developed involving solvent-free microwave
      irradiation. The new compounds were evaluated for their adenosine receptor (AR)
      affinities. The most potent derivatives contained a terminal tertiary amino
      function. Compounds with nanomolar AR affinities and at the same time high water
      solubility were obtained (A1 (Ki = 24-605 nM), A2A (Ki = 242-1250 nM), A2B (Ki =
      66-911 nM) and A3 (Ki = 155-1000 nM)). 2-(4-(2-(1,3-Dibutyl-2,4-dioxo-1,2,3,4,7,8
      hexahydropyrimido[2,1-f]purin-9(6H)-yl)ethyl)phenoxy)-N-(3
      (diethylamino)propyl)acetamide (27) and the corresponding N-(2-(pyrrolidin-1
      yl)ethyl)acetamide (36) were found to be the most potent antagonists of the
      present series. While 27 showed CYP inhibition and moderate metabolic stability,
      36 was found to possess suitable properties for in vivo applications. In an
      attempt to explain the affinity data for the synthesized compounds, molecular
      modeling and docking studies were performed using homology models of A1 and A2A
      adenosine receptors. The potent compound 36 was used as an example for discussion
      of the possible ligand-protein interactions. Moreover, the compounds showed high
      water-solubility indicating that the approach of introducing a basic side chain
      was successful for the class of generally poorly soluble AR antagonists.

PMID- 30108987
TI  - Synthesis and cellular penetration properties of new phosphonium based cationic
      amphiphilic peptides.
AB  - A new category of phosphonium based cationic amphiphilic peptides has been
      developed and evaluated as potential antimicrobial peptides and cell penetrating
      peptides. The required building blocks were conveniently accessible from cysteine
      and could be applied in a solid phase peptide synthesis protocol for
      incorporation into peptide sequences. Evaluation of the antimicrobial properties
      and cellular toxicity of these phosphonium based peptides showed that these
      "soft" cationic side-chain containing peptides have poor antimicrobial properties
      and most of them were virtually non toxic (on HEK cells tested at 256 and 512
      MUM) and non-haemolytic (on horse erythrocytes tested at 512 MUM), hinting at an
      interesting potential application as cell penetrating peptides. This possibility
      was evaluated using fluorescent peptide derivatives and showed that these
      phosphonium based peptide derivatives were capable of entering HEK cells and
      depending on the sequence confined to specific cellular areas.

PMID- 30108986
TI  - Evaluation of A-ring fused pyridine d-modified androstane derivatives for
      antiproliferative and aldo-keto reductase 1C3 inhibitory activity.
AB  - New A-ring pyridine fused androstanes in 17a-homo-17-oxa (d-homo lactone),
      17alpha-picolyl or 17(E)-picolinylidene series were synthesized and validated by
      X-ray crystallography, HRMS, IR and NMR spectroscopy. Novel compounds 3, 5, 8 and
      12 were prepared by treatment of 4-en-3-one or 4-ene-3,6-dione d-modified
      androstane derivatives with propargylamine catalyzed by Cu(ii), and evaluated for
      potential anticancer activity in vitro using human cancer cell lines and
      recombinant targets of steroidal anti-cancer drugs. Pyridine fusion to position
      3,4 of the A-ring may dramatically enhance affinity of 17alpha-picolyl compounds
      for CYP17 while conferring selective antiproliferative activity against PC-3
      cells. Similarly, pyridine fusion to the A-ring of steroidal d-homo lactones led
      to identification of new inhibitors of aldo-keto reductase 1C3, an enzyme
      targeted in acute myeloid leukemia, breast and prostate cancers. One A-pyridine d
      lactone steroid 5 also has selective submicromolar antiproliferative activity
      against HT-29 colon cancer cells. None of the new derivatives have affinity for
      estrogen or androgen receptors in a yeast screen, suggesting negligible
      estrogenicity and androgenicity. Combined, our results suggest that A-ring
      pyridine fusions have potential in modulating the anticancer activity of
      steroidal compounds.

PMID- 30108988
TI  - Novel 99mTc labelled complexes with 2-nitroimidazole isocyanide: design,
      synthesis and evaluation as potential tumor hypoxia imaging agents.
AB  - Radiolabelled 2-nitroimidazoles have been used for imaging hypoxia. With the aim
      of developing novel 99mTc radiotracers for imaging hypoxia, four novel 2
      nitroimidazole isocyanide derivatives (2a, 2b, 2c, and 2d) were synthesized and
      radiolabelling was carried out for preparing their corresponding 99mTc complexes.
      These 99mTc complexes were stable in vitro and could exhibit good hypoxic
      selectivity. The partition coefficient results indicated that they were
      hydrophilic, and an evaluation of biodistribution in mice bearing S180 tumors
      indicated that all of the complexes could accumulate in the tumors. Among them,
      99mTc-2c exhibited the highest tumor uptake and tumor/blood and tumor/muscle
      ratios at 2 h post-injection. Further, single photon emission computed tomography
      (SPECT) imaging studies indicated clear accumulation in tumors, suggesting that
      99mTc-2c was a promising candidate for hypoxia imaging.

PMID- 30108989
TI  - Effect of N-1 arylation of monastrol on kinesin Eg5 inhibition in glioma cell
      lines.
AB  - An original and focused library of two sets of dihydropyrimidin-2-thiones (DHPMs)
      substituted with N-1 aryl groups derived from monastrol was designed and
      synthesized in order to discover a more effective Eg5 ligand than the template.
      Based on molecular docking studies, four ligands were selected to perform
      pharmacological investigations against two glioma cell lines. The results led to
      the discovery of two original compounds, called 20h and 20e, with an anti
      proliferative effects, achieving IC50 values of about half that of the IC50 of
      monastrol in both cell lines. As with monastrol, flow cytometry analyses showed
      that the 20e and 20h compounds induced cell cycle arrest in the G2/M phase, and
      immunocytochemistry essays revealed the formation of monopolar spindles due to
      Eg5 inhibition without any toxicity to Caenorhabditis elegans.

PMID- 30108990
TI  - Assessment of the trifluoromethyl ketone functionality as an alternative zinc
      binding group for selective HDAC6 inhibition.
AB  - Recent studies point towards the possible disadvantages of using hydroxamic acid
      based zinc-binding groups in HDAC inhibitors due to e.g. mutagenicity issues. In
      this work, we elaborated on our previously developed Tubathian series, a class of
      highly selective thiaheterocyclic HDAC6 inhibitors, by replacing the
      benzohydroxamic acid function by an alternative zinc chelator, i.e., an aromatic
      trifluoromethyl ketone. Unfortunately, these compounds showed a reduced potency
      to inhibit HDAC6 as compared to their hydroxamic acid counterparts. In agreement,
      the most active trifluoromethyl ketone was unable to influence the growth of SK
      OV-3 ovarian cancer cells nor to alter the acetylation status of tubulin and
      histone H3. These data suggest that replacement of the zinc-binding hydroxamic
      acid function with a trifluoromethyl ketone zinc-binding moiety within reported
      benzohydroxamic HDAC6 inhibitors should not be considered as a standard strategy
      in HDAC inhibitor development.

PMID- 30108991
TI  - Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some
      diflunisal aza-analogs.
AB  - Our aim was to identify new multi-target compounds endowed with both anti
      inflammatory and anti-bacterial activities for treatment of human infections.
      Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed
      for its anti-virulence properties against methicillin-resistant Staphylococcus
      aureus. Effective synthesis of some aza-analogs of the anti-inflammatory drug
      diflunisal was carried out following the route involving key oxazole
      intermediates to obtain o- and m-hydroxypyridinecarboxylic acid derivatives. The
      newly synthesized diflunisal aza-analogs did not exhibit cytotoxic activity up to
      80 MUM and some of them exhibited anti-inflammatory activities, decreasing the
      levels of pro-inflammatory cytokines and prostaglandins induced by bacterial
      lipopolysaccharide in human primary macrophages. Ten of the diflunisal aza
      analogs were found to have interesting antibacterial activity, sensitizing S.
      aureus, Streptococcus pyogenes, Enterococcus faecium, and Pseudomonas aeruginosa
      to the antibacterial effects of beta-lactam antibiotics and protein synthesis
      inhibitors.

PMID- 30108993
TI  - Design and synthesis of conformationally constraint Dyrk1A inhibitors by creating
      an intramolecular H-bond involving a benzothiazole core.
AB  - We present the development of conformationally pre-organised Dyrk1A inhibitors
      based on the hydroxybenzothiazole urea scaffold. The modifications introduced to
      the discovered hit (AHS-211) proved the crucial role of the urea linker to
      preserve the bioactive conformation and led to the development of compound b5 as
      a promising selective Dyrk1A inhibitor.

PMID- 30108994
TI  - Discovery of novel picolinamide-based derivatives as novel VEGFR-2 kinase
      inhibitors: synthesis, in vitro biological evaluation and molecular docking.
AB  - Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a crucial role in
      tumor angiogenesis, and inhibition of the VEGFR-2 signaling pathway has emerged
      as an attractive target for cancer therapy. In our effort, a novel series of
      picolinamide-based derivatives were designed and synthesized as potent and
      effective VEGFR-2 inhibitors. All the newly prepared compounds were evaluated in
      vitro for their antiproliferative activity against A549 and HepG2 cell lines.
      Among the new compounds, 8j and 8l exhibited better activity against both A549
      and HepG2 cell lines. Molecular docking was performed to investigate the binding
      capacity and binding mode with VEGFR-2 (PDB code: ; 4ASD).

PMID- 30108992
TI  - The role of aryl-topology in balancing between selective and dual 5-HT7R/5-HT1A
      actions of 3,5-substituted hydantoins.
AB  - In order to search for active and selective serotonin 5-HT7R antagonists among
      3,5-disubstituted arylpiperazine-imidazolidine-2,4-diones, the role of the
      introduction/deletion and the mutual orientation of aromatic rings was analyzed.
      Chemical modifications of 2nd generation lead structure of 3-(3-(4
      (diphenylmethyl)piperazin-1-yl)-2-hydroxypropyl)-5-(4-fluorophenyl)-5
      methylimidazolidine-2,4-dione (2, KKB16) were performed. New derivatives (4-18)
      were designed and synthesized. X-ray crystallographic analysis of the
      representative compound 5-(4-fluorophenyl)-3-[2-hydroxy-3-(4-phenylpiperazin-1
      yl)propyl]-5-methylimidazolidine-2,4-dione (3) was performed to support molecular
      modeling and SAR studies. The affinity for 5-HT7R, D2R and 5-HT1AR in radioligand
      binding assays for the entire series and ADME-Tox parameters in vitro for
      selected compounds (7, 10, and 13) were evaluated. Molecular docking and
      pharmacophore model assessment were performed. According to the obtained results,
      5-methyl-5-naphthylhydantoin derivatives were found to be the new highly active 5
      HT7R agents (Ki <= 5 nM) with significant selectivity over 5-HT1AR and D2R. On
      the contrary, the (1-naphthyl)piperazine moiety was gained with the potent dual 5
      HT7R/5-HT1AR action (Ki: 11 nM/19 nM).

PMID- 30108995
TI  - Antitumor effects of melanin from Lachnum YM226 and its derivative in H22 tumor
      bearing mice.
AB  - In the present study, we investigated the anti-tumor activities of the
      intracellular homogeneous melanin (LM) of Lachnum YM226 and its derivative (ALM)
      on liver cancer using murine H22 hepatocarcinoma model. The results showed that
      LM and ALM (50 and 200 mg kg-1) could effectively inhibit tumor growth of H22
      tumour-bearing mice. The body weight, liver, spleen and thymus indices also
      improved in the LM and ALM treated groups. Moreover, the levels of alanine
      aminotransferase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase
      (ALP), creatinine (CRE), blood urea nitrogen (BUN) and uric acid (UA) were
      lowered. Serum cytokines of interleukin-2 (IL-2), interleukin-6 (IL-6), tumor
      necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were increased
      on LM and ALM administration, while LM and ALM significantly decreased the
      vascular endothelial growth factor (VEGF) and basic fibroblast growth factor
      (bFGF) levels. The H&E staining indicated that LM and ALM exhibited antitumor
      activity in vivo by promoting apoptosis and inhibiting angiogenesis. The anti
      tumor effect of ALM was more significant than that of LM for the same dose. In
      summary, the findings demonstrated that LM and ALM might be promising candidates
      for the prevention and treatment of HCC.

PMID- 30108996
TI  - Pharmacophore-based tailoring of biphenyl amide derivatives as selective 5
      hydroxytryptamine 2B receptor antagonists.
AB  - We designed and synthesized a new biphenyl amide-tryptamine hybrid molecule 7
      utilizing a pharmacophore-based approach as a 5-HT2B antagonist. The hybrid
      compound 7 was evaluated for its affinity to a panel of seven 5-HT receptors,
      demonstrating high selectivity for the 5-HT2B receptor. Functional assays
      revealed potent antagonism of 5-HT2B by 7 with an IC50 value of 14.1 nM.
      Moreover, compound 7 possessed a desirable in vitro pharmacokinetic profile and
      maintained its antagonistic potency in the presence of physiological
      concentrations of serum proteins. The design approach implemented in this
      investigation would facilitate the development of a second generation of highly
      selective and potent 5-HT2B antagonists.

PMID- 30108997
TI  - Design and synthesis of novel 1,3,5-triphenyl pyrazolines as potential anti
      inflammatory agents through allosteric inhibition of protein kinase Czeta
      (PKCzeta).
AB  - Much light has been shed on the vital role of protein kinase Czeta (PKCzeta) in
      NF-kappaB activation and the potential use of PKCzeta inhibitors as anti
      inflammatory agents. We previously reported a series of 1,3,5-trisubstituted
      pyrazolines as potent and selective allosteric inhibitors of PKCzeta; in that
      series of compounds, the phenolic OH at the 5-phenyl was essential for binding to
      the PKCzeta PIF pocket. In the present study, we surprisingly found that
      replacing it by a halogen and at the same time moving the OH to the 3-phenyl
      still resulted in active compounds. An extension of this class of compounds with
      a new focused library is presented herein, where the phenolic OH at the 5-phenyl,
      which was reported to be an irreplaceable feature for activity, was moved to the
      3-phenyl and replaced by halogen. The new set of compounds maintained the same
      level of potency against PKCzeta and selectivity against PKC isoforms, and showed
      reduced potency against the PIF pocket mutant PKCzeta[Val297Leu]. Of note, the
      repositioning of the key functional groups resulted in a marked enhancement of
      cellular potency. One of the most potent new PKCzeta inhibitors, 2h, was able to
      suppress NO production in RAW 264.7 macrophage cells with 8 times higher efficacy
      than the previous series, and inhibited the NF-kappaB transcriptional activity in
      U937 cells with a sub-micromolar IC50.

PMID- 30108999
TI  - Triazole-diindolylmethane conjugates as new antitubercular agents: synthesis,
      bioevaluation, and molecular docking.
AB  - We describe the synthesis of novel triazole-incorporated diindolylmethanes (DIMs)
      using a molecular hybridization approach. The in vitro antitubercular activity of
      the DIMs against Mycobacterium tuberculosis H37Ra (ATCC 25177) was tested in the
      active and dormant state. Among all the synthesized conjugates, the compounds 6b,
      6f, 6l, 6n, 6q, 6r, and 6s displayed good antitubercular activity against both
      the active and dormant Mtb H37Ra strain. The compound 6l exhibited good
      antitubercular activity against dormant Mtb H37Ra with an IC50 value of 1 MUg mL
      1 and IC90 (MIC) value of 3 MUg mL-1. The compounds 6b, 6l, and 6r displayed good
      antitubercular activity against active Mtb H37Ra with IC50 values of 2.19, 1.52,
      and 0.22 MUg mL-1, respectively. The compounds 6b, 6h, 6l, and 6s displayed more
      than 70% inhibition against the Gram-positive Bacillus subtilus strain at 3 MUg
      mL-1. The molecular docking study showed the binding modes of the titled
      compounds in the active site of the DprE1 enzyme and assisted with elucidating a
      structural basis for the inhibition of Mycobacteria.

PMID- 30109001
TI  - Identification of potent catalytic inhibitors of human DNA topoisomerase II by
      structure-based virtual screening.
AB  - Human DNA topoisomerase II (Top2) is a promising target for cancer treatment. To
      overcome the limitations of known Top2 inhibitors, novel Top2 catalytic
      inhibitors with new scaffolds were identified by structure-based virtual
      screening. In particular, compound 8 showed good in vitro antiproliferative
      activity with a broad spectrum. Top2-mediated cleavage assay and molecular
      modeling rationalized the mode of action. The new Top2 inhibitors are considered
      as good starting points for further hit-to-lead optimization in anticancer drug
      discovery.

PMID- 30108998
TI  - Chemical probes of Skp2-mediated p27 ubiquitylation and degradation.
AB  - Skp2 is a member of the F-box family of proteins that serve as substrate-specific
      adaptors in Skp1-CUL1-ROC1-F-box (SCF) E3 ubiquitin ligases. Skp2 (Fbxl1)
      directly binds to the tumor suppressor p27 in the context of the SCFSkp2 E3
      ubiquitin ligase to ubiquitylate and target-phosphorylated p27 for proteasomal
      degradation. As p27 is a powerful suppressor of growth in a variety of cells, and
      as Skp2 is also overexpressed in many human cancers, Skp2 is considered an
      oncogene and an intriguing drug target. However, despite 20 years of
      investigation, a valid chemical inhibitor of Skp2-mediated degradation of p27 has
      not been identified. Recently, an increasing number of compounds designed to have
      this bioactivity have been reported. Here, we conduct a meta-analysis of the
      evidence regarding bioactivity, structure, and medicinal chemistry in order to
      evaluate and compare these Skp2 inhibitor compounds. Despite chemically diverse
      compounds with a wide array of Skp2-mediated p27 ubiquitylation inhibition
      properties reported by several independent groups, no current chemical probe
      formally qualifies as a validated pharmaceutical hit compound. This finding
      suggests that our knowledge of the structural biochemistry of the Skp2-p27
      complex remains incomplete and highlights the need for novel modes of inquiry.

PMID- 30109000
TI  - Design, synthesis and bioactivity investigation of tetrandrine derivatives as
      potential anti-cancer agents.
AB  - Twenty-four 14-sulfonamide-tetrandrine derivatives as potential anti-cancer
      agents were synthesized. The synthetic derivatives were investigated for their
      cytotoxic activity against human cancer cell lines MDA-MB-231, PC3, WM9, HEL and
      K562. Initially, the IC50 values (50% inhibitory concentrations) of all of the
      compounds were determined. These derivatives exhibited potent, but distinct,
      inhibitory effects on the above-mentioned cell lines. Among them, compound 23,
      which was modified with a 2-naphthalenesulfonyl group at the 14-amino position,
      showed impressive inhibition of all five cancer cell lines, and especially of MDA
      MB-231 cells with an IC50 value of 1.18 +/- 0.14 MUM. Further mechanism
      exploration showed that 23 induced potent apoptotic cell death on MDA-MB-231
      cancer cells in a concentration-dependent manner. The results revealed that 23
      might be a potential anti-cancer drug candidate.

PMID- 30109003
TI  - Structure and properties of DOTA-chelated radiopharmaceuticals within the 225Ac
      decay pathway.
AB  - The successful delivery of toxic cargo directly to tumor cells is of primary
      importance in targeted (alpha) particle therapy. Complexes of radioactive atoms
      with the 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)
      chelating agent are considered as effective materials for such delivery
      processes. The DOTA chelator displays high affinity to radioactive metal isotopes
      and retains this capability after conjugation to tumor targeting moieties.
      Although the alpha-decay chains are well defined for many isotopes, the stability
      of chelations during the decay process and the impact of released energy on their
      structures remain unknown. The radioactive isotope 225Ac is an alpha-particle
      emitter that can be easily chelated by DOTA. However, 225Ac has a complex decay
      chain with four alpha-particle emissions during decay of each radionuclide. To
      advance our fundamental understanding of the consequences of alpha-decay on the
      stability of tumor-targeted 225Ac-DOTA conjugate radiopharmaceuticals, we
      performed first principles calculations of the structure, stability, and
      electronic properties of the DOTA chelator to the 225Ac radioactive isotope, and
      the initial daughters in the decay chain, 225Ac, 221Fr, 217At and 213Bi. Our
      calculations show that the atomic positions, binding energies, and electron
      localization functions are affected by the interplay between spin-orbit coupling,
      weak dispersive interactions, and environmental factors. Future empirical
      measurements may be guided and interpreted in light of these results.

PMID- 30109002
TI  - Targeting miRNA by tunable small molecule binders: peptidic aminosugar mediated
      interference in miR-21 biogenesis reverts epithelial to mesenchymal transition.
AB  - Epithelial to mesenchymal transition (EMT) is a process in which epithelial cells
      lose cell polarity and cell-cell adhesion and gain migratory and invasive
      properties to become mesenchymal cells that are very vital for development, wound
      healing and stem cell behavior and contribute pathologically to fibrosis and
      cancer progression. miR21, a potent regulator of the tumor suppressor gene PTEN,
      can be silenced to reverse EMT, thereby providing an attractive target for
      abrogating the malignant behavior of breast cancer. Here, we report the design,
      synthesis and binding of a peptidic-aminoglycoside (PA) based chemical library
      against pre-miR21 that led to the identification of a group of small molecules
      that bind to pre-miR21 with high affinities and antagonize miR-21 maturation and
      function, thereby reversing EMT. The approach described here offers a promising
      miRNA targeting platform where such aminosugar conjugates can be similarly used
      to target other oncogenic miRNAs. Minor changes in the amino acid sequence allow
      us to tailor the binding effectiveness and downstream biological effects, thus
      making this approach a potentially tunable method of regulation of miRNA
      function.

PMID- 30109005
TI  - Mercaptoacetate thioesters and their hydrolysate mercaptoacetic acids jointly
      inhibit metallo-beta-lactamase L1.
AB  - The 'superbug' infection caused by metallo-beta-lactamases (MbetaLs) including L1
      has grown into an emerging threat. To probe whether mercaptoacetate thioesters
      inhibiting L1 is a contribution of the thioester itself or its hydrolysate, ten
      mercaptoacetate thioesters 1-10 were synthesized, which specifically inhibited
      L1, exhibiting IC50 values ranging from 0.17 to 1.2 MUM, and 8 was found to be
      the best inhibitor (IC50 = 0.17 MUM). These thioesters restored the antimicrobial
      activity of cefazolin against E. coli expressing L1 by 2-4-fold. UV-vis
      monitoring showed that 1, 8 and 9 were unhydrolyzed in Tris buffer (pH 6.0-8.5),
      but hydrolyzed by L1; further HPLC monitoring indicated that 1/3 of the thioester
      9 was converted to mercaptoacetic acid. STD-NMR monitoring suggested that both
      the thioester and its hydrolysate mercaptoacetic acid jointly inhibited L1.

PMID- 30109004
TI  - Curcumin-based pyrazoline analogues as selective inhibitors of human monoamine
      oxidase A.
AB  - A series of 2-methoxy-4-(5-phenyl-4,5-dihydro-1H-pyrazol-3-yl)phenol (pyrazoline)
      derivatives (2-6) have been synthesized and tested for human monoamine oxidase
      (hMAO) inhibitory activity. The most active derivative (2) behaved as a
      competitive hMAO-A inhibitor, with an inhibition constant value of 0.08 MUM and a
      strong hMAO-A selectivity (Ki(hMAO-B)/Ki(hMAO-A) > 1751). In addition, 2
      exhibited little to no cytotoxic effects up to a 25 MUM concentration and
      provided the best blood-brain barrier permeability among the derivatives
      synthesized. Molecular dynamics simulations revealed that a chlorine substituent
      at the para-position of the phenyl ring in 2 enabled a pi-pi stacking interaction
      with Tyr407 and Tyr444 that resulted in the formation of an "aromatic sandwich"
      structure. Consequently, this tight-binding aromatic cage culminated in a
      dramatically reduced active site volume that is believed to be the origin of the
      observed selectivity between the hMAO-A and hMAO-B isozymes. Removal of the
      chlorine from 2 disrupted the favorable intermolecular interactions and resulted
      in a selectivity change towards hMAO-B.

PMID- 30109006
TI  - Structure-based virtual screening and ADME/T-based prediction analysis for the
      discovery of novel antifungal CYP51 inhibitors.
AB  - With the increasing incidence of pathogenic fungi and drug-resistant fungi in
      clinic, it has become very important to develop the novel rate-limiting enzyme
      14alpha-demethylase (CYP51) as an antifungal inhibitor. In this study, a method
      involving structure-based virtual screening was employed. First, a publicly
      available database was obtained from the Dow Chemical Company, and the database
      was screened by the designed pharmacophore model of CYP51 inhibitors. Then, the
      pharmacophore search hits were docked into the CYP51 crystal structure. Finally,
      sixteen compounds were selected for in vitro antifungal inhibition assay, and
      most of the compounds showed a certain degree of antifungal activity. In
      particular, compounds 3, 4, and 9 exhibited significant antifungal and anti-drug
      resistance activities by blocking the synthesis of ergosterol. The molecular
      docking and ADME/T properties of the compounds 3, 4, and 9 were further
      predicted, and the results indicated that they can form hydrophobic and
      coordination interactions with the active sites of CYP51. At the same time,
      compounds 4 and 9 showed promising drug-like properties. This study reveals that
      the compounds can be further optimized and developed as lead compounds.

PMID- 30109007
TI  - Efficient copper-catalyzed amination of DNA-conjugated aryl iodides under mild
      aqueous conditions.
AB  - Herein, we describe the development of copper-catalyzed cross-coupling of DNA
      conjugated aryl iodides with aliphatic amines. This protocol leverages a novel
      ligand, 2-((2,6-dimethoxyphenyl)amino)-2-oxoacetic acid, to effect the
      transformation in aqueous DMSO, under mild conditions and in air, making it an
      ideal candidate for the synthesis of DNA-encoded libraries.

PMID- 30109009
TI  - DIBI, a 3-hydroxypyridin-4-one chelator iron-binding polymer with enhanced
      antimicrobial activity.
AB  - Depriving microorganisms of bioavailable iron is a promising strategy for new
      anti-infective agents. The new, highly water-soluble, low molecular weight co
      polymer DIBI was developed to selectively bind iron(iii) ions as a tris chelate
      and acts as a standalone anti-infective. Minimum inhibitory concentration (MIC)
      studies show DIBI is effective against representative reference strains for Gram
      positive and Gram-negative bacteria S. aureus and A. baumannii, and the fungus C.
      albicans. Compared to the small molecule iron chelators, deferiprone and
      deferoxamine, DIBI outclassed these by factors of 100 to 1000 for inhibition of
      initial growth. DIBI and a series of related co-polymers (Mw of 2-9 kDa) were
      synthesized via reversible addition-fragmentation chain transfer (RAFT)
      polymerization of a chelating 3-hydroxypyridin-4-one (HPO) methacrylamide monomer
      and N-vinylpyrrolidone (NVP). Full incorporation of the HPO monomer into the co
      polymers from the reaction solution was determined by 1H NMR spectroscopy and
      ranged from 4.6 to 25.6 mol%. UV-vis spectroscopy showed that all the HPO in DIBI
      binds readily to iron(iii) in a tris chelate mode to the maximum theoretical
      iron(iii) binding capacity of the co-polymer. Chemical characterization including
      single crystal X-ray diffraction analyses of the O-benzyl protected and the
      functional HPO monomer are discussed. By design, DIBI is highly water soluble;
      the highest mass fraction in water tested was 70% w/w, without the need of
      organic co-solvents.

PMID- 30109008
TI  - Design, synthesis and biological evaluation of benzimidazole-rhodanine conjugates
      as potent topoisomerase II inhibitors.
AB  - In this study, a series of benzimidazole-rhodanine conjugates were designed,
      synthesized and investigated for their topoisomerase II (Topo II) inhibitory and
      cytotoxic activities. The results from Topo II-mediated pBR322 DNA relaxation and
      cleavage assays showed that the synthesized compounds might act as Topo II
      catalytic inhibitors. Certain compounds displayed potent Topo II inhibition at 10
      MUM. The cytotoxic activities of these compounds against HeLa, A549, Raji, PC-3,
      MDA-MB-201, and HL-60 cancer cell lines were evaluated. The results indicated
      that these compounds exhibited strong antiproliferative activity. A good
      relationship was observed between the Topo II inhibitory potency and the
      cytotoxicity of these compounds. The structure-activity relationship revealed
      that the electronic effects, the phenyl group, and the rhodanine moiety were
      particularly important for the Topo II inhibitory potency and cytotoxicity.

PMID- 30109011
TI  - Generation of a long-acting fusion inhibitor against HIV-1.
AB  - AIDS has evolved from a fatal infectious disease to a manageable chronic disease
      under the treatment of anti-AIDS medications. HIV fusion inhibitors with high
      activity, low side effects and strong selectivity are promising drugs against
      HIV. Only one fusion inhibitor is currently approved, thereby highly active long
      acting fusion inhibitors need to be developed for long-term AIDS treatment. Here,
      we synthesised MT-SC22EK (a small HIV fusion inhibitor) derivatives containing 1
      2 staples to improve its stability. Antiviral activity studies showed that MT
      SC22EK-2 with two staples exhibited potent inhibitory activity against HIV-1
      standard strains and Chinese epidemic strains, and at the same time, MT-SC22EK-2
      presented strong anti-T20 resistance. Surprisingly, MT-SC22EK-2 possessed
      excellent protease stability with a half-life of 3665 min. MT-SC22EK-2 is a
      potential HIV fusion inhibitor considered as a long-acting anti-HIV drug
      candidate.

PMID- 30109010
TI  - Discovery of a tetrazolyl beta-carboline with in vitro and in vivo
      osteoprotective activity under estrogen-deficient conditions.
AB  - beta-Carbolines have been assessed for osteoclastogenesis. However, their effect
      on osteoblasts during estrogen deficiency is still unclear. Here, a series of
      novel piperazine and tetrazole tag beta-carbolines have been synthesized and
      examined for osteoblast differentiation in vitro. In vitro data suggest that
      compound 8g is the most promising osteoblast differentiating agent that was
      evaluated for in vivo studies. Compound 8g promoted osteoblast mineralization,
      stimulated Runx2, BMP-2 and OCN expression levels, increased BrdU incorporation
      and inhibited generation of free radicals as well as nitric oxide. Since a
      piperazine group is involved in bone repair activity and beta-carboline in
      IkappaB kinase (IKK) inhibition, compound 8g inhibited tumor necrosis factor
      alpha (TNFalpha) directed IkappaBalpha phosphorylation, preventing nuclear
      translocation of NF-kappaB thereby alleviating osteoblast apoptosis. In vivo
      studies show that compound 8g was able to restore estrogen deficiency-induced
      bone loss in ovariectomized rats without any toxicity, thus signifying its
      potential in bone-protection chemotherapy under postmenopausal conditions.

PMID- 30109012
TI  - Synthesis and antiplasmodial activity of purine-based C-nucleoside analogues.
AB  - A series of homologous C-nucleoside mimics have been synthesized via an efficient
      and facile synthetic protocol involving the conjugate addition of purine to sugar
      derived olefinic ester in good yields. The synthesized compounds were evaluated
      for their antiplasmodial activity in vitro against both the CQ-sensitive and
      resistant strains of P. falciparum. Interestingly, all the synthesized nucleoside
      analogs exhibited an IC50 of <5 MUM, while compounds 22a, 23a, and 23b showed
      promising antiplasmodial activity with an IC50 of 1.61, 0.88, and 1.01 MUM
      against the CQ-sensitive Pf3D7 strain and 1.14, 1.01, and 2.57 MUM against the CQ
      resistant PfK1 strain, respectively.

PMID- 30109013
TI  - Phenotypic plasticity in response to temperature fluctuations is genetically
      variable, and relates to climatic variability of origin, in Arabidopsis thaliana.
AB  - Under current climate change, increasing mean temperatures are not only causing
      hotter summers, but temperature variability is increasing as well. Phenotypic
      plasticity can help plants to overcome negative effects of temperature
      variability and allow them to rapidly adjust traits to adverse conditions.
      Moreover, genetic variation in such plasticity could provide potential for
      adaptive evolution in response to changing climate variability. Here, we
      conducted an experiment with 11 Arabidopsis thaliana genotypes to investigate
      intraspecific variation in plant responses to two aspects of variable temperature
      stress: timing and frequency. We found that the timing but not frequency of
      temperature stress affected the phenology, growth, reproduction and allocation
      strategy of plants, and that genotypes differed substantially in their responses.
      Moreover, trait plasticity was positively related to precipitation variability of
      origin, suggesting an adaptive role of plasticity. Our results indicate that the
      developmental stage of a plant during heat stress is a key determinant of its
      response, and that plasticity to temperature variability is an evolving and
      possibly adaptive trait in natural populations of A. thaliana. More generally,
      our study demonstrates the usefulness of studying plant responses to climatic
      variability per se, given that climatic variability is predicted to increase in
      the future.

PMID- 30109014
TI  - The Importance of Amodal Completion in Everyday Perception.
AB  - Amodal completion is the representation of those parts of the perceived object
      that we get no sensory stimulation from. In the case of vision, it is the
      representation of occluded parts of objects we see: When we see a cat behind a
      picket fence, our perceptual system represents those parts of the cat that are
      occluded by the picket fence. The aim of this piece is to argue that amodal
      completion plays a constitutive role in our everyday perception and trace the
      theoretical consequences of this claim.

PMID- 30109016
TI  - Fibrous dysplasia and Klippel-Trenaunay syndrome: a rare association.
AB  - Fibrous dysplasia is a rare congenital disorder, with abnormal hypertrophy of
      affected bone. A 17-year-old girl with a protrusion on her right forehead
      presented and was diagnosed as craniofacial fibrous dysplasia. Although she had
      no gait problem, her right leg was longer than the other. She had vascular
      malformation on the right leg. The condition was diagnosed as Klippel-Trenaunay
      syndrome, which also is a rare disorder. As the prevalence of these disorders is
      scarce, the probability of coincidental association of them is extremely low. No
      previous report about the association of fibrous dysplasia and Klippel-Trenaunay
      syndrome could be found. We concluded that, those two rare congenital disorders
      arose coincidentally in this patient.

PMID- 30109015
TI  - Assumed Lighting Direction in the Interpretation of Cast Shadows.
AB  - Assumed lighting direction in cast-shadow interpretation was investigated.
      Experiment 1 used an ambiguous object-shadow-matching task to measure bias in
      shadow-matching direction. The shadow-matching bias was largest when the lighting
      direction was on average 38.3 degrees  left from above (a median of 25.1 degrees
      ). Experiment 2 tested the effect of body posture (head orientation) on cast
      shadow interpretation using stimuli aligned in a head-centrically vertical or
      horizontal orientation. The below-shadow (light-from-above) bias in the head
      centric frame was robust across the sitting upright, reclining-on-the-left-side,
      reclining-on-the-right-side, and supine conditions. A right-shadow (light-from
      left) bias in the head-centric frame was found for the sitting upright and
      reclining-on-the-right-side conditions. In the reclining-on-the-left-side
      condition, shadow biases to the gravitational below direction and head-centric
      right direction may have cancelled each other out. These results are consistent
      with findings from previous shape-from-shading studies, suggesting that the same
      light-source assumption is applied to shading and shadow interpretations.

PMID- 30109018
TI  - Laboratory growth of denitrifying water column microbial consortia from deep-sea
      shipwrecks in the northern Gulf of Mexico.
AB  - BACKGROUND: Shipwrecks serve as a rich source for novel microbial populations
      that have largely remained undiscovered. Low temperatures, lack of sunlight, and
      the availability of substrates derived from the shipwreck's hull and cargo may
      provide an environment in which microbes can develop unique metabolic
      adaptations.   Methods: To test our hypothesis that shipwrecks could influence
      the microbial population involved in denitrification when a consortium is grown
      in the laboratory, we collected samples proximate to two steel shipwrecks in the
      northern Gulf of Mexico. Then under laboratory conditions, we grew two
      independent denitrifying microbial consortia. Each consortium was grown by using
      the BART assay system and analyzed based on growth kinetics, ion chromatography
      and 16S amplicon sequencing. RESULTS: Both denitrifying consortia were different
      from each other based on varied growth profiles, rates of nitrate utilization and
      16S amplicon sequencing. CONCLUSIONS: Our observations conclude that the
      laboratory grown water column microbial consortia from deep-sea shipwrecks in the
      Gulf of Mexico are able to undergo aggressive denitrification.

PMID- 30109017
TI  - Best practice data life cycle approaches for the life sciences.
AB  - Throughout history, the life sciences have been revolutionised by technological
      advances; in our era this is manifested by advances in instrumentation for data
      generation, and consequently researchers now routinely handle large amounts of
      heterogeneous data in digital formats. The simultaneous transitions towards
      biology as a data science and towards a 'life cycle' view of research data pose
      new challenges. Researchers face a bewildering landscape of data management
      requirements, recommendations and regulations, without necessarily being able to
      access data management training or possessing a clear understanding of practical
      approaches that can assist in data management in their particular research
      domain. Here we provide an overview of best practice data life cycle approaches
      for researchers in the life sciences/bioinformatics space with a particular focus
      on 'omics' datasets and computer-based data processing and analysis. We discuss
      the different stages of the data life cycle and provide practical suggestions for
      useful tools and resources to improve data management practices.

PMID- 30109020
TI  - Current overview and treatment of mantle cell lymphoma.
AB  - Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with historically
      poor long-term survival compared with other B-cell malignancies. Treatment
      strategies for this disease are variable and dependent on symptoms and patient
      fitness. Despite recent advances, MCL remains incurable and patients with high
      risk disease have particularly poor outcomes. This review focuses on recent
      developments that enhance our understanding of the biology of MCL and new
      treatment approaches that have led to substantial improvements in clinical
      outcomes. We will outline induction immuno-chemotherapy and maintenance
      strategies in transplant-eligible patients. In addition, effective strategies for
      patients unfit for intensive induction will be discussed, with a particular focus
      on novel molecular therapies with activity in MCL. Lastly, a number of ongoing
      clinical trials will be presented; the data from these trials are anticipated to
      redefine standards of care in the near future.

PMID- 30109019
TI  - Recent advances in understanding bile duct remodeling and fibrosis.
AB  - Cholestatic liver disease encompasses a detrimental group of diseases that are
      non-discriminatory in nature. These diseases occur over every age range from
      infancy (biliary atresia) to geriatrics (hepatitis). They also cover both genders
      in the form of primary sclerosing cholangitis in men and primary biliary
      cholangitis in women. Oftentimes, owing to the disease progression and extensive
      scarring, the treatment of last resort becomes a liver transplant. In this
      review, we will briefly discuss and explore new avenues of understanding in the
      progression of cholestatic liver disease and possible therapeutic targets for
      intervention. The greater our understanding into the idiopathic nature of
      cholestatic liver disease, the better our chances of discovering treatment
      options to halt or reverse the progression, reducing or eliminating the need for
      expensive and risky transplants.

PMID- 30109021
TI  - Recent advances in the management of malignant pheochromocytoma and
      paraganglioma: focus on tyrosine kinase and hypoxia-inducible factor inhibitors.
AB  - Inactivating mutations of the succinate dehydrogenase subunit B ( SDHB) gene and
      the subsequent stabilization and activation of the hypoxia-inducible factor 2
      alpha (HIF2alpha) unit are recognized hallmarks associated with the development
      of metastatic pheochromocytomas and paragangliomas (MPPG). Despite this
      discovery, the development of systemic therapies for patients with MPPG has been
      very slow. The rarity of the disease, the lack of preclinical animal models, and
      the impracticable development of large clinical trials has hindered the
      therapeutic progress for MPPG. Chemotherapy and low-specific activity 131meta
      iodo-benzyl-guanidine (MIBG) (manufactured by simple isotope exchange
      methodology) led to positive clinical responses in about a third of patients.
      Molecular targeted therapies were introduced into oncological clinical practice
      at the beginning of the 21st century. These therapies have been demonstrated to
      be effective for patients with cancers that previously exhibited limited
      responses to systemic chemotherapy, such as kidney and thyroid carcinomas and
      pancreatic neuroendocrine tumors. The pathogenesis of MPPG overlaps in some way
      with the pathogenesis of kidney, medullary thyroid, and pancreatic neuroendocrine
      carcinomas, providing scientific support to explore molecular targeted therapies
      such as tyrosine kinase and HIF inhibitors.

PMID- 30109023
TI  - The unique role of cardiovascular magnetic resonance imaging in acute
      myocarditis.
AB  - This article addresses the specific diagnostic information provided by
      cardiovascular magnetic resonance (CMR) in patients with suspected acute
      myocarditis. It gives an overview of the current evidence of the ability of CMR
      to detect myocardial inflammation and discusses the added value as well as its
      limitations in clinical settings. Because of the large variety of symptoms and
      the limited specificity of other non-invasive procedures, the identification of
      myocardial inflammation is of paramount importance. Because of its accuracy in
      imaging ventricular volumes and function and its unique ability to visualize
      myocardial edema, scar, and other tissue abnormalities, CMR has emerged as the
      prime non-invasive diagnostic tool in patients with acute myocarditis. The
      presence of myocardial inflammation is not specific to viral myocarditis or other
      forms of acute myocardial injury, and the regional distribution within the
      myocardium helps differentiate acute myocarditis from other diseases. The
      currently recommended diagnostic criteria (Lake Louise Criteria) include markers
      for hyperemia/capillary leak, edema, and inflammatory scarring. Their diagnostic
      accuracy of close to 80% is satisfactory to rule in myocarditis, yet the negative
      predictive value is less than 70%. Novel CMR techniques, especially T1 and T2
      mapping, have been shown to further improve the diagnostic utility.

PMID- 30109022
TI  - Advances in risk stratification of bladder cancer to guide personalized medicine.
AB  - Bladder cancer is a heterogeneous disease that poses unique challenges to the
      treating clinician. It can be limited to a relatively indolent papillary tumor
      with low potential for progression beyond this stage to muscle-invasive disease
      prone to distant metastasis. The former is best treated as conservatively as
      possible, whereas the latter requires aggressive surgical intervention with
      adjuvant therapies in order to provide the best clinical outcomes. Risk
      stratification traditionally uses clinicopathologic features of the disease to
      provide prognostic information that assists in choosing the best therapy for each
      individual patient. For bladder cancer, this informs decisions regarding the type
      of intravesical therapy that is most appropriate for non-muscle-invasive disease
      or whether or not to administer neoadjuvant chemotherapy prior to radical
      cystectomy. More recently, tumor genetic sequencing data have been married to
      clinical outcomes data to add further sophistication and personalization. In the
      next generation of risk classification, we are likely to see the inclusion of
      molecular subtyping with specific treatment considerations based on a tumor's
      mutational profile.

PMID- 30109025
TI  - UTAUT for HSS: initial framework to study health IT adoption in the developing
      countries.
AB  - Unified Theory of Acceptance and Use of Technology (UTAUT) is an integrative
      concept that has been used widely to measure IT adoption. However, a recent study
      in a developing country concluded that UTAUT is not adequate in predicting IT
      adoption within the context of health system strengthening (HSS). It has been
      suggested that context-specific dimensions to modify UTAUT should be considered.
      The objective of this paper is to propose an extension of the theory, called
      UTAUT for HSS, as a reference for contextualizing health system variables for
      health IT adoption studies in the developing countries. We combined the multi
      level framework of UTAUT with WHO health system building blocks. Modification of
      the original multi-level framework was performed on the 3 levels. i.e:  the
      higher-level contextual factors, middle-level, and individual-level contextual
      factors. Based on this, we propose a modified multi-level framework of technology
      acceptance and use for health system strengthening setting (UTAUT for HSS). 
      Given the complexities of health systems, more thoughts regarding the
      methodologies will be useful to enrich this initial framework.  Commentaries and
      discussions are invited for improvement, before implementation to obtain more
      complete story of health IT adoption in the low resources setting.

PMID- 30109024
TI  - Recent advances in understanding the mechanisms of cerebellar granule cell
      development and function and their contribution to behavior.
AB  - The cerebellum is the focus of an emergent series of debates because its
      circuitry is now thought to encode an unexpected level of functional diversity.
      The flexibility that is built into the cerebellar circuit allows it to
      participate not only in motor behaviors involving coordination, learning, and
      balance but also in non-motor behaviors such as cognition, emotion, and spatial
      navigation. In accordance with the cerebellum's diverse functional roles, when
      these circuits are altered because of disease or injury, the behavioral outcomes
      range from neurological conditions such as ataxia, dystonia, and tremor to
      neuropsychiatric conditions, including autism spectrum disorders, schizophrenia,
      and attention-deficit/hyperactivity disorder. Two major questions arise: what
      types of cells mediate these normal and abnormal processes, and how might they
      accomplish these seemingly disparate functions? The tiny but numerous cerebellar
      granule cells may hold answers to these questions. Here, we discuss recent
      advances in understanding how the granule cell lineage arises in the embryo and
      how a stem cell niche that replenishes granule cells influences wiring when the
      postnatal cerebellum is injured. We discuss how precisely coordinated
      developmental programs, gene expression patterns, and epigenetic mechanisms
      determine the formation of synapses that integrate multi-modal inputs onto single
      granule cells. These data lead us to consider how granule cell synaptic
      heterogeneity promotes sensorimotor and non-sensorimotor signals in behaving
      animals. We discuss evidence that granule cells use ultrafast neurotransmission
      that can operate at kilohertz frequencies. Together, these data inspire an
      emerging view for how granule cells contribute to the shaping of complex animal
      behaviors.

PMID- 30109027
TI  - Morphology and performance of polyvinyl chloride membrane modified with Pluronic
      F127.
AB  - Background: Attempts to modify the morphology of membrane for application in
      industrial separation are being undertaken by many researchers. The present study
      discusses the morphological modification of polyvinyl chloride (PVC) membrane by
      combining the hydrophilic surfactant Pluronic F127 (PF127) in a polymer solution
      to improve the performance of the membrane.  Method: The membrane is formed using
      the non-solvent induced-phase separation (NIPS) method. PF127 is added to the
      membrane solution as a membrane modifying agent. The effects of the surfactant
      concentration in the dope solution on the permeability of pure water, solute
      rejection, hydrophilic characteristics, and membrane morphology are investigated.
      Results: Higher concentrations of PF127 had a significant effect on the
      permeability of pure water. The highest membrane permeation was 45.65 l/m
      2.hr.atm with the addition of 7% PF127 additive. Conclusion: PF127 is
      successfully proposed as a membrane pore-forming agent in this work; the blending
      of this additive in appropriate amounts in the polymer solution is adequate to
      improve the performance of the PVC membrane.

PMID- 30109026
TI  - Challenges in the use of atomistic simulations to predict solubilities of drug
      like molecules.
AB  - Background: Solubility is a physical property of high importance to the
      pharmaceutical industry, the prediction of which for potential drugs has so far
      been a hard task. We attempted to predict the solubility of acetylsalicylic acid
      (ASA) by estimating the absolute chemical potentials of its most stable polymorph
      and of solutions with different concentrations of the drug molecule. Methods:
      Chemical potentials were estimated from all-atom molecular dynamics simulations. 
      We used the Einstein molecule method (EMM) to predict the absolute chemical
      potential of the solid and solvation free energy calculations to predict the
      excess chemical potentials of the liquid-phase systems. Results: Reliable
      estimations of the chemical potentials for the solid and for a single ASA
      molecule using the EMM required an extremely large number of intermediate states
      for the free energy calculations, meaning that the calculations were extremely
      demanding computationally. Despite the computational cost, however, the computed
      value did not agree well with the experimental value, potentially due to
      limitations with the underlying energy model. Perhaps better values could be
      obtained with a better energy model; however, it seems likely computational cost
      may remain a limiting factor for use of this particular approach to solubility
      estimation.    Conclusions: Solubility prediction of drug-like solids remains
      computationally challenging, and it appears that both the underlying energy model
      and the computational approach applied may need improvement before the approach
      is suitable for routine use.

PMID- 30109028
TI  - PDZD8 is not the 'functional ortholog' of Mmm1, it is a paralog.
AB  - Authors of a recent paper demonstrate that, like ERMES (ER-mitochondria encounter
      structure) in fungal cells, PDZD8 (PDZ domain containing 8) tethers mitochondria
      to the ER in mammalian cells. However, identifying PDZD8 as a "functional
      ortholog" of yeast Mmm1 (maintenance of mitochondrial morphology protein 1) is at
      odds with the phylogenetic data. PDZD8 and Mmm1 are paralogs, not orthologs,
      which affects the interpretation of the data with respect to the evolution of ER
      mitochondria tethering. Our phylogenetic analyses show that PDZD8 co-occurs with
      ERMES components in lineages closely related to animals solidifying its identity
      as a paralog of Mmm1. Additionally, we identify two related paralogs, one
      specific to flagellated fungi, and one present only in unicellular relatives of
      animals. These results point to a complex evolutionary history of ER-mitochondria
      tethering involving multiple gene gains and losses in the lineage leading to
      animals and fungi.

PMID- 30109029
TI  - Antimicrobial resistance of Pasteurella multocida strains isolated from pigs
      between 2010 and 2016.
AB  - Pasteurella multocida is one of the significant causes of respiratory infection
      outbreaks in the Korean pig industry. Although antimicrobial treatment is an
      effective strategy for controlling respiratory diseases, limited information is
      available regarding the antimicrobial susceptibility of the pathogens infecting
      Korean pigs. Therefore, in this study, we evaluated the antimicrobial resistance
      of P multocida against widely used antimicrobials in order to enable the
      selection of appropriate drugs and to evaluate any trends in resistance. A total
      of 454 isolates of P multocida were collected from all provinces in Korea between
      2010 and 2016. Antimicrobial susceptibility of all isolates was determined using
      a broth microdilution method. The most frequently observed resistance was to
      sulphadimethoxine (76.0 per cent), followed by oxytetracycline (66.5 per cent),
      chlortetracycline (36.8 per cent) and florfenicol (18.5 per cent). Although no
      consistent increase or decrease in resistance was observed for most
      antimicrobials, resistance to fluoroquinolones tended to increase over the study
      period. A variety of resistance patterns were observed, most frequently for
      tetracyclines and sulphonamides. These findings could provide information
      enabling the selection of optimal antimicrobials for efficient treatment of
      pneumoniae pasteurellosis in pig farms, which would impede the emergence of
      antimicrobial resistance.

PMID- 30109031
TI  - The encaged lung: rapidly progressive idiopathic pleurisy.
AB  - A 56-year-old, non-smoker male with no exposure, presented with right chest pain
      and a huge loss in forced vital capacity due to right lung volume reduction with
      consensual pleural thickening on high-resolution computed tomography. All
      serological and microbiological tests were negative. The surgical lung biopsy
      showed fibrinous pleurisy while the search for neoplastic cells resulted
      negative. Because of symptoms worsening he started low dose steroids without
      benefits until he died 3 months later for cardiac ischemic attack. We reviewed
      the literature to identify possible etiologies and a rapidly progressive
      idiopathic pleurisy revealed to be the most probable diagnosis.

PMID- 30109030
TI  - Post-transplant lymphoproliferative disorder presenting on post-transplant Day 35
      as a pulmonary parenchymal infiltrate-a case report.
AB  - Post-transplant lymphoproliferative disorder (PTLD), a rare but serious
      complication of solid organ transplantation, is classified into early-onset and
      late-onset subtypes. Early-onset PTLD occurs a median of 4-11 months after lung
      transplantation. It rarely presents in the first 2 months post-transplant. Early
      onset PTLD usually presents as a solitary pulmonary nodule. We present a unique
      case of early-onset PTLD that was diagnosed on post-operative Day 35 and
      presented as a pulmonary parenchymal infiltrate. This case is also exceptional in
      that the patient had a significant clinical response to only a single dose of
      rituximab.

PMID- 30109032
TI  - 'Balanced ischaemia' on ECG in dual territory STEMI.
AB  - Culprit lesion identification in ST elevation myocardial infarction (STEMI) is
      often guided by electrocardiogram (ECG) changes. However, in the setting of multi
      vessel coronary artery occlusion, this can be challenging. We describe an
      interesting case of dual territory STEMI with unanticipated ECG changes that
      bring forth the concept of 'balanced ischaemia'. These seemingly bizarre findings
      are well explained using the fundamentals of electrocardiography reinstating its
      relevance in modern day cardiology.

PMID- 30109033
TI  - A novel acid catalyst based on super/subcritical CO2-enriched water for the
      efficient esterification of rosin.
AB  - Rosin esters are widely applied as masticatory substances and beverage
      stabilizers, while classical acid-catalysed processes will lead to metal residue
      or environmental issues. Super/subcritical CO2-enriched high temperature liquid
      water (HTLW) as a green acid catalyst in the esterification reaction of rosin
      with glycerol was investigated. The pH of CO2-H2O binary system, as calculated
      based on gas-liquid equilibrium, charge balance and chemical equilibrium
      equations, ranged from 3.49 to 3.70 depending on the reaction conditions,
      indicating effective acid catalysis. Response surface methodology experiments
      showed the optimum conditions were 3.5 h, 3.9 MPa CO2 pressure, a rosin-to
      glycerol molar ratio of 1.32 and 269 degrees C, and an enhanced esterification
      yield of 94.74% was achieved, which was superior to that obtained using a ZnO
      catalyst. It was found that the esterification kinetics was a pseudo first-order
      reaction, and the enthalpy and entropy of activation were calculated using the
      Arrhenius-Polanyi equation. The presence of super/subcritical CO2-enriched HTLW
      catalyst can decrease the activation energy and significantly accelerate the
      reaction rate.

PMID- 30109034
TI  - Simultaneous inpainting and denoising by directional global three-part
      decomposition: connecting variational and Fourier domain-based image processing.
AB  - We consider the very challenging task of restoring images (i) that have a large
      number of missing pixels, (ii) whose existing pixels are corrupted by noise, and
      (iii) that ideally contain both cartoon and texture elements. The combination of
      these three properties makes this inverse problem a very difficult one. The
      solution proposed in this manuscript is based on directional global three-part
      decomposition (DG3PD) (Thai, Gottschlich. 2016 EURASIP. J. Image Video
      Process.2016, 1-20 (doi:10.1186/s13640-015-0097-y)) with a directional total
      variation norm, directional G-norm and linfinity-norm in the curvelet domain as
      key ingredients of the model. Image decomposition by DG3PD enables a decoupled
      inpainting and denoising of the cartoon and texture components. A comparison with
      existing approaches for inpainting and denoising shows the advantages of the
      proposed method. Moreover, we regard the image restoration problem from the
      viewpoint of a Bayesian framework and we discuss the connections between the
      proposed solution by function space and related image representation by harmonic
      analysis and pyramid decomposition.

PMID- 30109036
TI  - Defining the risk landscape in the context of pathogen pollution: Toxoplasma
      gondii in sea otters along the Pacific Rim.
AB  - Pathogens entering the marine environment as pollutants exhibit a spatial
      signature driven by their transport mechanisms. The sea otter (Enhydra lutris), a
      marine animal which lives much of its life within sight of land, presents a
      unique opportunity to understand land-sea pathogen transmission. Using a dataset
      on Toxoplasma gondii prevalence across sea otter range from Alaska to California,
      we found that the dominant drivers of infection risk vary depending upon the
      spatial scale of analysis. At the population level, regions with high T. gondii
      prevalence had higher human population density and a greater proportion of human
      dominated land uses, suggesting a strong role for population density of the felid
      definitive host of this parasite. This relationship persisted when a subset of
      data were analysed at the individual level: large-scale patterns in sea otter T.
      gondii infection prevalence were largely explained by individual exposure to
      areas of high human housing unit density, and other landscape features associated
      with anthropogenic land use, such as impervious surfaces and cropping land. These
      results contrast with the small-scale, within-region analysis, in which age, sex
      and prey choice accounted for most of the variation in infection risk, and
      terrestrial environmental features provided little variation to help in
      explaining observed patterns. These results underscore the importance of spatial
      scale in study design when quantifying both individual-level risk factors and
      landscape-scale variation in infection risk.

PMID- 30109035
TI  - Mapping movement, mood, motivation and mentation in the subthalamic nucleus.
AB  - The anatomical connections of the subthalamic nucleus (STN) have driven
      hypotheses about its functional anatomy, including the hypothesis that the
      precise anatomical location of STN deep brain stimulation (DBS) contributes to
      the variability of motor and non-motor responses across patients with Parkinson's
      disease (PD). We previously tested the hypothesis using a three-dimensional (3D)
      statistical method to interpret the acute effects of unilateral DBS at each
      patient's clinically optimized DBS settings and active contact. Here, we report a
      similar analysis from a new study in which DBS parameters were standardized and
      DBS locations were chosen blind to clinical response. In 74 individuals with PD
      and STN DBS, STN contacts were selected near the dorsal and ventral borders of
      the STN contralateral to the more affected side of the body. Participants were
      tested off PD medications in each of three unilateral DBS conditions (ventral STN
      DBS, dorsal STN DBS and DBS off) for acute effects on mood, apathy, working
      memory, response inhibition and motor function. Voltage, frequency and pulse
      width were standardized, and participants and raters were blind to condition. In
      a categorical analysis, both dorsal and ventral STN DBS improved mean motor
      function without affecting cognitive measures. Ventral STN DBS induced greater
      improvement in rigidity and anxiety than dorsal STN DBS. In the 3D analysis,
      contact location was significant for body hypokinesia, rigidity and resting
      tremor, with the greatest improvement occurring with DBS in dorsal STN and zona
      incerta. The 3D results provide new, direct functional evidence for the
      anatomically derived model of STN, in which motor function is best represented in
      dorsal STN. However, our data suggest that functional segregation between motor
      and non-motor areas of the STN is limited, because locations that induced
      improvements in motor function and mood overlapped substantially.

PMID- 30109038
TI  - Femtosecond laser-assisted synthesis of silver nanoparticles and reduced graphene
      oxide hybrid for optical limiting.
AB  - Reduced graphene oxide (rGO) functionalized with silver nanoparticles (Ag NPs) is
      prepared using a femtosecond laser ablation in liquids method. By ablating the
      mixed aqueous solutions of silver nitrate and graphene oxide (GO) using
      femtosecond laser pulses, Ag ions and GO are simultaneously reduced and well
      dispersed Ag NPs supported on rGO are obtained. The effect of laser power,
      irritation time and Ag ion concentration on the optical property and morphology
      of the products are systematically studied. The nonlinear optical responses of
      the functionalized graphene are studied using a nanosecond Z-scan technique. The
      rGO hybrid shows an enhanced nonlinear absorption (NLA) effect compared with GO
      and rGO, and thus exhibits an excellent optical limiting (OL) property with very
      low activating threshold, which is estimated to be about 0.38 J cm-2. The
      enhanced NLA effect in rGO hybrids makes it possible to fabricate solid-state
      optical limiter, improving the practicality of graphene materials in the OL area.

PMID- 30109037
TI  - New sporopollenin-based beta-cyclodextrin functionalized magnetic hybrid
      adsorbent for magnetic solid-phase extraction of nonsteroidal anti-inflammatory
      drugs from water samples.
AB  - A magnetic solid-phase extraction (MSPE) procedure on the newly synthesized
      magnetic beta-cyclodextrin functionalized with toluene diisocyanate (TDI) as a
      linker and further modified with bio-polymeric spores of sporopollenin (MSp-TDI
      betaCD), was developed for the extraction of nonsteroidal anti-inflammatory drugs
      (NSAIDs), namely, indoprofen (INP), ketoprofen (KTP), ibuprofen (IBP) and
      fenoprofen (FNP) from water samples prior to their HPLC-DAD determination. The
      newly synthesized MSp-TDI-betaCD was comprehensibly characterized using FT-IR,
      XRD, SEM-EDX, BET and VSM analyses. The separation of selected NSAIDs on MSp-TDI
      betaCD from aqueous solution was simply achieved by applying an external magnetic
      field via a permanent magnet. The MSPE parameters affecting extraction
      performance, i.e. sorbent dosage, sample volume, extraction and desorption time,
      type of organic eluent and volume and solution pH were investigated and
      optimized. The proposed method showed linear range between 0.5 and 500 ng ml-1,
      low limit of detection at S/N = 3 (0.16-0.37 ng ml-1) and limit of quantification
      at S/N = 10 (0.53-1.22 ng ml-1). The inter-day (n = 15) and intra-day (n = 5)
      precision for the proposed methods given by relative standard deviation (RSD%)
      was in the range of 2.5-4.0 and 2.1-5.5, respectively. The extraction recoveries
      of NSAIDs from environmental samples (tap, drinking and river water) ranged from
      92.5% to 123.6%, with satisfactory precision (RSD% less than 12.4%).

PMID- 30109039
TI  - Causal reasoning in rats' behaviour systems.
AB  - Conceiving of stimuli and responses as causes and effects, and assuming that rats
      acquire representational models of causal relations from Pavlovian procedures,
      previous work by causal model theory proponents attempted to train rat subjects
      to represent stimulus A as a cause of both stimulus B and food. By these
      assumptions, with formal help from Bayesian networks, self-production of stimulus
      B should reduce expectation of alternative causes, including stimulus A, and
      their effects, including food. Reduced feeder-directed responding to stimulus B
      when self-produced has been taken as evidence for a general causal reasoning
      capacity among rats involving mental maps of causal relations. Critics have
      rejoined that response competition can explain these effects. The present
      research replicates the key effect, but uses continuous and finer-grained
      measurement of a broader range of behaviours. Behaviours not recorded in previous
      studies contradict both prior explanations. Even results cited in support of
      these explanations, when measured in finer detail and continuously over longer
      periods, show patterns not expected by either view, but supportive of a specific
      process approach with attention to motivational factors. Still, the abstract
      prediction from Bayesian networks holds, providing a potentially complementary
      normative analysis. Behaviour systems theory provides firmer framing for such
      theories than representational-map alternatives.

PMID- 30109040
TI  - A new insight into the evolution and functional divergence of FRK genes in Pyrus
      bretschneideri.
AB  - In plants, plant fructokinases (FRKs) are considered to be the main gateway of
      fructose metabolism as they can phosphorylate fructose to fructose-6-phosphate.
      Chinese white pears (Pyrus bretschneideri) are one of the popular fruits in the
      world market; sugar content is an important factor affecting the quality of the
      fruit. We identified 49 FRKs from four Rosaceae species; 20 of these sequences
      were from Chinese white pear. Subsequently, phylogenic relationship, gene
      structure and micro-collinearity were analysed. Phylogenetic and exon-intron
      analysis classified these FRKs into 10 subfamilies, and it was aimed to further
      reveal the variation of the gene structure and the evolutionary relationship of
      this gene family. Remarkably, gene expression patterns in different tissues or
      different development stages of the pear fruit suggested functional redundancy
      for PbFRKs derived from segmental duplication or genome-wide duplication and sub
      functionalization for some of them. Additionally, PbFRK11, PbFRK13 and PbFRK16
      were found to play important roles in regulating the sugar content in the fruit.
      Overall, this study provided important insights into the evolution of the FRK
      gene family in four Rosaceae species, and highlighted its roles in both pear
      tissue and fruits. Results presented here provide the appropriate candidate of
      PbFRKs that might contribute to fructose efflux in the pear fruit.

PMID- 30109042
TI  - Optimizing the route for production of activated carbon from Casuarina
      equisetifolia fruit waste.
AB  - This work deals with optimizing the conditions of pyrolysis and type of activator
      to upgrade the use of Casuarina equisetifolia fruit waste (CFW) as available and
      a potential precursor, in production of activated carbon (AC). In this respect,
      the route of activation was carried out through one- and two-step pyrolysis
      processes, using different chemical activating agents, such as H3PO4, KOH and
      ZnCl2. The performance of the CFW-based ACs is assessed by estimating the physico
      chemical characteristics (pH, electrical conductivity, bulk density and
      hardness), surface morphology and scanning electron microscopy, together with
      carbon yield, surface area and adsorption performance of pollutants in aqueous
      medium (methylene blue, iodine and molasses colour removal efficiencies). The
      results show that the two-step activation process was more effective than one
      step activation for providing high adsorption performance CFW-based ACs. The
      maximum Brunauer-Emmett-Teller surface area 547.89 m2 g-1 was produced by using
      H3PO4 activating agents, and applied two-step pyrolysis. According to the
      American Water Work Association and based on bulk density of the investigated
      ACs, we recommend that most of produced ACs are suitable for treating waste
      water.

PMID- 30109041
TI  - The effect of domestication on post-conflict management: wolves reconcile while
      dogs avoid each other.
AB  - Highly cooperative social species are expected to engage in frequent
      reconciliation following conflicts in order to maintain pack cohesiveness and
      preserve future cooperation. By contrast, in social species with low reliance on
      cooperation, reconciliation is expected to be less frequent. Here, we investigate
      the pattern of reconciliation in four captive wolf packs and four captive dog
      packs. We provide evidence for reconciliation in captive wolves, which are highly
      dependent on cooperation between pack members, while domestic dogs, which rely on
      conspecific cooperation less than wolves, avoided interacting with their partners
      after conflicts. Occurrence, intensity, latency, duration and initiation of wolf
      reconciliations appeared to vary as a consequence of a compromise between the
      costs (e.g. risk of further aggression) and the benefits (e.g. restoring
      relationship with opponents) of such interactions. Our results are in line with
      previous findings on various wolf packs living under different social and
      ecological conditions, suggesting that reconciliation is an important strategy
      for maintaining functional relationships and pack cohesiveness. However, current
      results on dogs are in contrast to the only other study showing that
      reconciliation can occur also in this species. Therefore, the occurrence of
      reconciliation in dogs may be influenced by social and environmental conditions
      more than in wolves. Which factors promote and modulate reconciliation in dogs
      needs to be further investigated.

PMID- 30109043
TI  - BNPd single-atom catalysts for selective hydrogenation of acetylene to ethylene:
      a density functional theory study.
AB  - The mechanisms of selective hydrogenation of acetylene to ethylene on B11N12Pd
      single-atom catalyst were investigated through the density functional theory by
      using the 6-31++G** basis set. We studied the adsorption characteristics of H2
      and C2H2, and simulated the reaction mechanism. We discovered that H2 underwent
      absolute dissociative chemisorption on single-atom Pd, forming the B11N12Pd(2H)
      dihydride complex, and then the hydrogenation reaction with C2H2 proceeded. The
      hydrogenation reaction of acetylene on the B11N12Pd complex complies with the
      Horiuti-Polanyi mechanism, and the energy barrier was as low as 26.55 kcal mol-1.
      Meanwhile, it also has a higher selectivity than many bimetallic alloy single
      atom catalysts.

PMID- 30109044
TI  - NMR-based metabolomic profiling of Peganum harmala L. reveals dynamic variations
      between different growth stages.
AB  - Xerophytes play an active role in preventing soil denudation and desertification
      in arid and semi-arid areas. Peganum harmala L. (Zygophyllaceae family), a
      seasonally growing, poisonous and drought-tolerant plant, is widely distributed
      in the Xinjiang Uygur Autonomous Region and used as a traditional herbal medicine
      as well as, in winter, a fodder source. Previous research has focused on the
      pharmacological activity of isolated compounds and stress responses to growth
      environments. However, the metabolic profile of P. harmala and variations in its
      metabolites, including medicinally active and stress resistance components, have
      not been illustrated during different growth stages. Here, we collected plant
      samples in May, August, October and December. We determined the metabolic
      composition of methanol extracts using NMR spectroscopy, and comparisons of four
      growth stages were accomplished by applying statistical analysis. The results
      showed that vasicine, choline and sucrose were significantly elevated in samples
      harvested in May. Significantly higher amounts of betaine, lysine, 4
      hydroxyisoleucine and proline were found in samples collected in August than in
      samples collected in other months, and the concentrations of phosphorylcholine,
      glucose, acetic acid and vasicinone were highest in December. The relationships
      between differential biomarkers and plant physiological states affected by
      diverse growth environmental factors were discussed. Our result deepened the
      understanding of metabolic mechanisms in plant development and confirmed the
      advantage of using NMR-based metabolomic treatments in quality evaluation when P.
      harmala is used for different purposes.

PMID- 30109046
TI  - Bistable fully developed mixed convection flow with viscous dissipation in a
      vertical channel.
AB  - It is shown that unstable dual solutions in fully developed mixed convection flow
      in a vertical channel disappear in the presence of relatively strong thermal
      radiation. In this case, we have a unique stable flow at each pressure gradient.
      When the effect of thermal radiation is weak another branch of stable solutions
      is created, resulting in bistable flows. In this case, the flow exhibits
      hysteresis with variation of the pressure gradient. Optically, a thin radiation
      model is used.

PMID- 30109045
TI  - Impact of the springtail's cuticle nanotopography on bioadhesion and biofilm
      formation in vitro and in the oral cavity.
AB  - Springtails (Collembola) have a nanostructured cuticle. To evaluate and to
      understand anti-biofouling properties of springtail cuticles' morphology under
      different conditions, springtails, shed cuticles and cuticle replicates were
      studied after incubation with protein solutions and bacterial cultures using
      common in vitro models. In a second step, they were exposed to human oral
      environment in situ in order to explore potential application in dentistry. In
      vitro, the cuticular structures were found to resist wetting by albumin solutions
      for up to 3 h and colonization by Staphylococcus epidermidis was inhibited. When
      exposed in the oral cavity, initial pellicle formation was of high heterogeneity:
      parts of the surface were coated by adsorbed proteins, others remained uncoated
      but exhibited locally attached, 'bridging', proteinaceous membranes spanning
      across cavities of the cuticle surface; this unique phenomenon was observed for
      the first time. Also the degree of bacterial colonization varied considerably. In
      conclusion, the springtail cuticle partially modulates bioadhesion in the oral
      cavity in a unique and specific manner, but it has no universal effect.
      Especially after longer exposure, the nanotextured surface of springtails is
      masked by the pellicle, resulting in subsequent bacterial colonization, and,
      thus, cannot effectively avoid bioadhesion in the oral cavity comprehensively.
      Nevertheless, the observed phenomena offer valuable information and new
      perspectives for the development of antifouling surfaces applicable in the oral
      cavity.

PMID- 30109048
TI  - Compilation and evaluation of gas phase diffusion coefficients of halogenated
      organic compounds.
AB  - Organic halogens are of great environmental and climatic concern. In this work,
      we have compiled their gas phase diffusivities (pressure-normalized diffusion
      coefficients) in a variety of bath gases experimentally measured by previous
      studies. It is found that diffusivities estimated using Fuller's semi-empirical
      method agree very well with measured values for organic halogens. In addition, we
      find that at a given temperature and pressure, different molecules exhibit very
      similar mean free paths in the same bath gas, and then propose a method to
      estimate mean free paths in different bath gases. For example, the pressure
      normalized mean free paths are estimated to be 90, 350, 90, 80, 120 nm atm in air
      (and N2/O2), He, argon, CO2 and CH4, respectively, with estimated errors of
      around +/-25%. A generic method, which requires less input parameter than
      Fuller's method, is proposed to calculate gas phase diffusivities. We find that
      gas phase diffusivities in He (and air as well) calculated using our method show
      fairly good agreement with those measured experimentally and estimated using
      Fuller's method. Our method is particularly useful for the estimation of gas
      phase diffusivities when the trace gas contains atoms whose diffusion volumes are
      not known.

PMID- 30109047
TI  - Intra-individual variation in performance on novel variants of similar tasks
      influences single factor explanations of general cognitive processes.
AB  - Intra-individual variation in performance within and across cognitive domains may
      confound interpretations of both domain-general and domain-specific abilities.
      Such variation is rarely considered in animal test batteries. We investigate
      individual consistency in performance by presenting pheasant chicks (n = 31),
      raised under standardized conditions, with nine different cognitive tasks. Among
      these tasks were two replicated novel variants of colour learning and colour
      reversal problems, tests of positional learning and memory, as well as two
      different tasks that captured multiple putative measures of inhibitory control
      and motor-related performance. These task variants were also used to compare
      subjects' performance on alternative test batteries comprised of different task
      combinations. Subjects' performance improved with experience, yet we found
      relatively little consistency in their performance, both within similar tasks
      using different paradigms and across different tasks. Parallel analysis revealed
      non-significant factors when all nine tasks were included in a principal axis
      factor analysis. However, when different combinations of six of the nine tasks
      were included in principal axis factoring, 14 of 84 combinations revealed
      significant main factors, explaining between 28 and 35% of the variance in task
      performance. While comparable findings have been suggested to reflect domain
      general intelligence in other species, we found no evidence to suggest that a
      single factor encompassed a diverse range of cognitive abilities in pheasants.
      Instead, we reveal how single factor explanations of cognitive processes can be
      influenced by test battery composition and intra-individual variation in
      performance across tasks. Our findings highlight the importance of conducting
      multiple tests within specific domains to ensure robust cognitive measures are
      obtained.

PMID- 30109049
TI  - Frequency dispersion reveals chromophore diversity and colour-tuning mechanism in
      parrot feathers.
AB  - Variation in animal coloration is often viewed as the result of chemically
      distinct pigments conferring different hues. The role of molecular environment on
      hue tends to be overlooked as analyses are mostly performed on free pigments
      extracted from the integument. Here we analysed psittacofulvin pigments within
      parrot feathers to explore whether the in situ organization of pigments may have
      an effect on hue. Resonance Raman spectra from a red region of a yellow-naped
      amazon Amazona auropalliata tail feather show frequency dispersion, a phenomenon
      that is related to the presence of a range of molecular conformations (and
      multiple chromophores) in the pigment, whereas spectra from a yellow region on
      the same feather do not show the same evidence for multiple chromophores. Our
      findings are consistent with non-isomeric psittacofulvin pigments behaving as a
      single chromophore in yellow feather barbs, which implies that psittacofulvins
      are dispersed into a structurally disordered mixture in yellow feathers compared
      with red feathers. Frequency dispersion in red barbs may instead indicate that
      pigments are structurally organized through molecule-molecule interactions. Major
      differences in the hues of parrot feathers are thus associated with differences
      in the organization of pigments within feathers.

PMID- 30109050
TI  - Comprehensive diagnosis of PCDD/F emission from three hazardous waste
      incinerators.
AB  - Comprehensive diagnosis of polychlorinated dibenzo-p-dioxin and dibenzofuran
      (PCDD/F) emissions was systematically conducted on three hazardous waste
      incinerators (HWIs). Results indicated that PCDD/F mainly existed in the solid
      phase before the bag filter. This was especially true for higher chlorinated
      dioxin and furan congeners (hexa-, hepta- and octa-). The aged bag filters tended
      to increase the gas-phase PCDD/F. Emissions also increased due to PCDD/F
      desorption from circulated scrubbing solution and plastic packing media used in
      the wet scrubber. The PCDD/F concentrations were elevated during the start-up
      process, reaching up to 5.4 times higher than those measured during the normal
      operating period. The ratios of PCDFs/PCDDs revealed that the surface-catalysed
      de novo synthesis was the dominant pathway of PCDD/F formation. Installation of
      more efficient fabric filters, intermittent replacement of circulated scrubbing
      solution will result in reduced PCDD/F emission. Additionally, 2,3,4,7,8-PeCDF
      correlated well with the international toxic equivalent quantity (I-TEQ) value,
      which suggests that 2,3,4,7,8-PeCDF could act as an I-TEQ indicator.

PMID- 30109051
TI  - Appetitive information seeking behaviour reveals robust daily rhythmicity for
      Internet-based food-related keyword searches.
AB  - There has been an exponential growth of information seeking behaviour (ISB) via
      Internet-based programs over the past decade. The availability of software that
      record ISB temporal patterns has provided a valuable opportunity to examine
      biological rhythms in human behaviour. Internet search repositories, such as
      Google Trends, permit the analyses of large datasets that can be used to track
      ISB on a domestic and international scale. We examined daily and seasonal Google
      Trends search patterns for keywords related to food intake, using the most
      relevant search terms for the USA, UK, Canada, India and Australia. Daily and
      seasonal ISB rhythmicity were analysed using CircWave v. 1.4. Daily ISB data
      revealed a robust and significant sine waveform for general terms (e.g. 'pizza
      delivery') and country-specific search terms (e.g. 'just eat'). The pattern
      revealed clear evening double-peaks, occurring every day at 19.00 and 02.00. The
      patterns were consistent across search terms, days of the week and geographical
      locations, suggesting a common ISB rhythm that is not necessarily culture
      dependent. Then, we conducted Cosinor v. 2.4 analyses to examine the daily
      amplitudes in ISB. The results indicated a non-significant linear increased from
      Monday to Sunday. Seasonal data did not show consistent significant ISB patterns.
      It is likely that two different human populations are responsible for the daily
      'early' and 'late' evening ISB peaks. We propose that the major factor that
      contributes to the bimodal evening peak is age-dependent (e.g. adolescent, early
      adulthood versus midlife and mature adulthood) and a minor role for human
      chronotypes (e.g. late versus early). Overall, we present novel human appetitive
      behaviour for information seeking of food resources and propose that Internet
      based search patterns reflect a biological rhythm of motivation for energy
      balance.

PMID- 30109052
TI  - Students' learning style detection using tree augmented naive Bayes.
AB  - Students are characterized according to their own distinct learning styles.
      Discovering students' learning style is significant in the educational system in
      order to provide adaptivity. Past researches have proposed various approaches to
      detect the students' learning styles. Among all, the Bayesian network has emerged
      as a widely used method to automatically detect students' learning styles. On the
      other hand, tree augmented naive Bayesian network has the ability to improve the
      naive Bayesian network in terms of better classification accuracy. In this paper,
      we evaluate the performance of the tree augmented naive Bayesian in automatically
      detecting students' learning style in the online learning environment. The
      experimental results are promising as the tree augmented naive Bayes network is
      shown to achieve higher detection accuracy when compared to the Bayesian network.

PMID- 30109053
TI  - Flexible decision-making in grooming partner choice in sooty mangabeys and
      chimpanzees.
AB  - Living in permanent social groups forces animals to make decisions about when,
      how and with whom to interact, requiring decisions to be made that integrate
      multiple sources of information. Changing social environments can influence this
      decision-making process by constraining choice or altering the likelihood of a
      positive outcome. Here, we conceptualized grooming as a choice situation where an
      individual chooses one of a number of potential partners. Studying two wild
      populations of sympatric primate species, sooty mangabeys (Cercocebus atys atys)
      and western chimpanzees (Pan troglodytes verus), we tested what properties of
      potential partners influenced grooming decisions, including their relative value
      based on available alternatives and the social relationships of potential
      partners with bystanders who could observe the outcome of the decision. Across
      1529 decision events, multiple partner attributes (e.g. dominance ranks, social
      relationship quality, reproductive state, partner sex) influenced choice.
      Individuals preferred to initiate grooming with partners of similar global rank,
      but this effect was driven by a bias towards partners with a high rank compared
      to other locally available options. Individuals also avoided grooming partners
      who had strong social relationships with at least one bystander. Results
      indicated flexible decision-making in grooming interactions in both species,
      based on a partner's value given the local social environment. Viewing partner
      choice as a value-based decision-making process allows researchers to compare how
      different species solve similar social problems.

PMID- 30109055
TI  - Intercomparison of photogrammetry software for three-dimensional vegetation
      modelling.
AB  - Photogrammetry-based three-dimensional reconstruction of objects is becoming
      increasingly appealing in research areas unrelated to computer vision. It has the
      potential to facilitate the assessment of forest inventory-related parameters by
      enabling or expediting resource measurements in the field. We hereby compare
      several implementations of photogrammetric algorithms (CMVS/PMVS, CMPMVS, MVE,
      OpenMVS, SURE and Agisoft PhotoScan) with respect to their performance in
      vegetation assessment. The evaluation is based on (i) a virtual scene where the
      precise location and dimensionality of objects is known a priori and is thus
      conducive to a quantitative comparison and (ii) using series of in situ acquired
      photographs of vegetation with overlapping field of view where the
      photogrammetric outcomes are compared qualitatively. Performance is quantified by
      computing receiver operating characteristic curves that summarize the type-I and
      type-II errors between the reference and reconstructed tree models. Similar
      artefacts are observed in synthetic- and in situ-based reconstructions.

PMID- 30109054
TI  - Synergistic effect of eicosapentaenoic acid-enriched phospholipids and sea
      cucumber saponin on orotic acid-induced non-alcoholic fatty liver disease in
      rats.
AB  - Non-alcoholic fatty liver disease (NAFLD) is becoming an increasingly prevalent
      chronic liver disease all over the world. The present study was undertaken to
      explore the synergistic effects of sea cucumber saponins (SCS) and
      eicosapentaenoic acid-enriched phospholipids (EPA-PL) at ratios of 0.5 : 0.5 and
      1 : 1 on NAFLD and demonstrate possible protective mechanisms. It was found that
      the combination of EPA-PL and SCS at half dose exhibited better effects than EPA
      PL or SCS alone and the combination of EPA-PL and SCS at full dose in alleviating
      orotic acid (OA)-induced symptoms including growth parameters, serum parameters
      and liver function. Further evaluation of the mechanism illustrated that EPA-PL
      and SCS combination at the ratio of 0.5 : 0.5 could markedly reduce the mRNA
      expressions of fatty acid synthase, acetyl-CoA carboxylase, glucose-6-phosphate
      dehydrogenase and malic enzyme genes and significantly increase expression of
      genes relevant to fatty acid beta-oxidation including peroxisome proliferator
      activated receptor and its target genes (CPT1, CPT2 and ACOX1), suggesting that
      the protection of the EPA-PL and SCS combination at the ratio of 0.5 : 0.5
      against OA-induced NAFLD might be mainly via lipogenesis inhibition and beta
      oxidation enhancement in the liver. The synergistic effects of EPA-PL and SCS
      make it possible to reduce the doses of EPA-PL or SCS to avoid side effects,
      which is of value for the development of dietary supplements or functional foods
      for preventing or treating NAFLD.

PMID- 30109056
TI  - The leading-edge vortex on a rotating wing changes markedly beyond a certain
      central body size.
AB  - Stable attachment of a leading-edge vortex (LEV) plays a key role in generating
      the high lift on rotating wings with a central body. The central body size can
      affect the LEV structure broadly in two ways. First, an overall change in the
      size changes the Reynolds number, which is known to have an influence on the LEV
      structure. Second, it may affect the Coriolis acceleration acting across the
      wing, depending on the wing-offset from the axis of rotation. To investigate
      this, the effects of Reynolds number and the wing-offset are independently
      studied for a rotating wing. The three-dimensional LEV structure is mapped using
      a scanning particle image velocimetry technique. The rapid acquisition of images
      and their correlation are carefully validated. The results presented in this
      paper show that the LEV structure changes mainly with the Reynolds number. The
      LEV-split is found to be only minimally affected by changing the central body
      radius in the range of small offsets, which interestingly includes the range for
      most insects. However, beyond this small offset range, the LEV-split is found to
      change dramatically.

PMID- 30109057
TI  - First-principles calculations of structural, electronic, magnetic and elastic
      properties of Mo2FeB2 under high pressure.
AB  - The structural, electronic, magnetic and elastic properties of Mo2FeB2 under high
      pressure have been investigated with first-principles calculations. Furthermore,
      the thermal dynamic properties of Mo2FeB2 were also studied with the quasi
      harmonic Debye model. The volume of Mo2FeB2 decreases with the increase in
      pressure. Using the analysis of the density of the states, atom population and
      Mulliken overlap population, it is observed that as the pressure increases, the B
      B bonds are strengthened and the B-Mo covalency decreases. Moreover, for all
      pressures, Mo2FeB2 is detected in the anti-ferromagnetic phase and the magnetic
      moments decrease with the increase in pressure. The calculated bulk modulus,
      shear modulus, Young's modulus, Poisson's ratio and universal anisotropy index
      all increase with the increase in pressure. From thermal expansion coefficient
      analysis, it is found that Mo2FeB2 shows good volume invariance under high
      pressure and temperature. The examination of the dependence of heat capacity on
      the temperature and pressure shows that heat capacity is more sensitive to
      temperature than to pressure.

PMID- 30109058
TI  - Growth profiling, kinetics and substrate utilization of low-cost dairy waste for
      production of beta-cryptoxanthin by Kocuria marina DAGII.
AB  - The dairy industry produces enormous amount of cheese whey containing the major
      milk nutrients, but this remains unutilized all over the globe. The present study
      investigates the production of beta-cryptoxanthin (beta-CRX) by Kocuria marina
      DAGII using cheese whey as substrate. Response surface methodology (RSM) and an
      artificial neural network (ANN) approach were implemented to obtain the maximum
      beta-CRX yield. Significant factors, i.e. yeast extract, peptone, cheese whey and
      initial pH, were the input variables in both the optimizing studies, and beta-CRX
      yield and biomass were taken as output variables. The ANN topology of 4-9-2 was
      found to be optimum when trained with a feed-forward back-propagation algorithm.
      Experimental values of beta-CRX yield (17.14 mg l-1) and biomass (5.35 g l-1)
      were compared and ANN predicted values (16.99 mg l-1 and 5.33 g l-1,
      respectively) were found to be more accurate compared with RSM predicted values
      (16.95 mg l-1 and 5.23 g l-1, respectively). Detailed kinetic analysis of
      cellular growth, substrate consumption and product formation revealed that growth
      inhibition took place at substrate concentrations higher than 12% (v/v) of cheese
      whey. The Han and Levenspiel model was the best fitted substrate inhibition model
      that described the cell growth in cheese whey with an R2 and MSE of 0.9982% and
      0.00477%, respectively. The potential importance of this study lies in the
      development, optimization and modelling of a suitable cheese whey supplemented
      medium for increased beta-CRX production.

PMID- 30109059
TI  - The effect of cathodal transcranial direct current stimulation during rapid eye
      movement sleep on neutral and emotional memory.
AB  - Sleep-dependent memory consolidation has been extensively studied. Neutral
      declarative memories and serial reaction time task (SRTT) performance can benefit
      from slow-wave activity, characterized by less than 1 Hz frequency cortical slow
      oscillations (SO). Emotional memories can benefit from theta activity,
      characterized by 4-8 Hz frequency cortical oscillations. Applying transcranial
      direct current stimulation (tDCS) during sleep entrains specific frequencies to
      alter sleep architecture. When applying cathodal tDCS (CtDCS), neural inhibition
      or excitation may depend on the waveform at the applied frequency. A double
      dissociation was predicted, with CtDCS at SO frequency improving neutral
      declarative memory and SRTT performance, and theta frequency CtDCS inhibiting
      negative emotional memory. Participants completed three CtDCS conditions (Theta:
      5 Hz, SO: 0.75 Hz and control: sham) and completed an SRTT and word recognition
      task pre- and post-sleep, comprising emotional and neutral words to assess
      memory. In line with predictions, CtDCS improved neutral declarative memory when
      applied at SO frequency. When applied at theta frequency, no negative emotional
      word memory impairment was found but a positive association was found between
      post-stimulation theta power and emotional word recognition. SRTT performance was
      also not altered by either CtDCS frequency. Future studies should investigate
      overnight theta CtDCS and examine the effects of CtDCS during and after
      stimulation.

PMID- 30109060
TI  - Towards hydrophobic carminic acid derivatives and their incorporation in
      polyacrylates.
AB  - Carminic acid, a natural hydrophilic dye extensively used in the food and
      cosmetic industries, is converted in hydrophobic dyes by acetylation or
      pivaloylation. These derivatives are successfully used as biocolourants for
      rubber objects. In this paper, spectroscopic properties of the carminic acid
      derivatives in dimethyl sulfoxide and in polybutylacrylate are studied by means
      of photoluminescence and time-resolved photoluminescence decays, revealing a
      hypsochromic effect due to the presence of bulky substituents as the acetyl or
      pivaloyl groups. Molecular mechanics and density functional theory calculations
      confirm the disruption of planarity between the sugar ring and the anthraquinoid
      system determined by the esterification.

PMID- 30109061
TI  - Filtration-induced production of conductive/robust Cu films on cellulose paper by
      low-temperature sintering in air.
AB  - Cellulose paper is an attractive substrate for paper electronics because of its
      advantages of flexibility, biodegradability, easy incorporation into composites,
      low cost and eco-friendliness. However, the micrometre-sized pores of cellulose
      paper make robust/conductive films difficult to deposit onto its surface from
      metal-nanoparticle-based inks. We developed a Cu-based composite ink to deposit
      conductive Cu films onto cellulose paper via low-temperature sintering in air.
      The Cu-based inks consisted of a metallo-organic decomposition ink and formic
      acid-treated Cu flakes. The composite ink was heated in air at 100 degrees C for
      only 15 s to give a conductive Cu film (7 * 10-5 Omega cm) on the cellulose
      paper. Filtration of the Cu-based composite ink accumulated Cu flakes on the
      paper, which enabled formation of a sintered Cu film with few defects. A strategy
      was developed to enhance the bending stability of the sintered Cu films on paper
      substrates using polyvinylpyrrolidone-modified Cu flakes and amine-modified
      paper. The resistance of the Cu films increased only 1.3-fold and 1.1-fold after
      1000 bending cycles at bending radii of 5 mm and 15 mm, respectively. The results
      of this study provide an approach to increasing the bending stability of Cu films
      on cellulose paper.

PMID- 30109063
TI  - Influence of silicon on growth mechanism of micro-arc oxidation coating on cast
      Al-Si alloy.
AB  - Micro-arc oxidation (MAO) is a plasma-assisted electrochemistry method to prepare
      protective ceramic coatings on aluminium alloys. Alloy elements of the Al-alloy
      substrate, such as Si, Cu, Mg and Li, have effects on the microstructure and
      composition of the MAO coatings. Usually, silicon distributes in the cast Al-Si
      alloy substrate as small laths and they cover approximately 10% of the substrate
      surface. Therefore, their effects on the growth process and microstructure of the
      MAO coatings are worthy of notice. In the present study, oxide coatings with a
      thickness of 15-18 um were prepared on the ZL109 Al-Si alloy by MAO. The phase
      content, surface morphology and element distribution of the coatings were
      investigated by X-ray diffraction, grazing incidence X-ray diffraction, scanning
      electron microscope, and electron probe micro-analysis respectively. The average
      hardness of the coatings was 622.3 +/- 10.2 HV0.05. The adhesive strength of the
      coatings is 40.55 +/- 2.55 N, and the adhesion of the coatings could be rated as
      5B by tape test according to ASTM D3359-17 standard test methods, which indicated
      a high adhesive strength between the MAO coating and substrate. The effects of
      silicon laths on surface morphology and composition of the coatings were
      discussed, and a model was put forward to describe the growth process of the MAO
      coatings on cast Al-Si alloys. The authors believe that the high silicon content
      of the substrate has no adverse influence on the structure and properties of the
      MAO coating on the ZL109 alloy.

PMID- 30109062
TI  - Peptidomics of potato protein hydrolysates: implications of post-translational
      modifications in food peptide structure and behaviour.
AB  - Post-translational modifications (PTMs) often occur in proteins and play a
      regulatory role in protein function. There is an increasing interest in the
      bioactivity of food protein-derived peptides, but the occurrence of PTMs and
      their influence on food peptide structure and behaviour remain largely unknown.
      In this study, the shotgun-based peptidomics strategy was used to identify the
      occurrence of PTMs in peptides generated from potato protein hydrolysis using
      digestive proteases. Diverse PTMs were found in the potato peptides, including
      acetylation of lysine, N-terminal of proteins and peptides, C-terminal amidation,
      de-amidation of asparagine/glutamine, methylation and trimethylation, methionine
      oxidation and N-terminal pyro-glutamyl residue formation. The modifications may
      have been formed naturally or as a result of chemical reactions during isolation
      and enzymatic processing of the potato proteins. Most of the PTMs were calculated
      to decrease the isoelectric point and increase molecular hydrophobicity of the
      peptides, which will influence their bioactivity while also potentially altering
      their solubility in an aqueous environment. This is the first study to unravel
      that food-derived peptides can be widely modified by PTMs associated with notable
      changes in peptide chemical properties. The findings have broader implications on
      the bioavailability, biomolecular interactions and biological activities of food
      peptides.

PMID- 30109064
TI  - A long-forgotten 'dinosaur' bone from a museum cabinet, uncovered to be a Japan's
      iconic extinct mammal, Paleoparadoxia (Desmostylia, Mammalia).
AB  - Here, we report a new 'discovery' of a desmostylian fossil in the geological
      collection at a national university in Japan. This fossil was unearthed over 60
      years ago and donated to the university. Owing to the original hand-written note
      kept with the fossil in combination with interview investigation, we were able to
      reach two equally possible fossil sites in the town of Tsuchiyu Onsen, Fukushima.
      Through the interviews, we learned that the fossil was discovered during
      construction of a debris flow barrier and that it was recognized as a 'dinosaur'
      bone among the locals and displayed in the Village Hall before/until the town
      experienced a fire disaster in 1954. As scientific findings, the fossil was
      identified to be a right femur of Paleoparadoxia (Desmostylia), which shows well
      preserved muscle scars on the surface. The age was estimated to be 15.9 Ma or
      younger in zircon-dating. This study shows an excellent case that historical and
      scientific significances could be extracted from long-forgotten uncatalogued
      specimens as long as the original information is retained with the specimens.

PMID- 30109065
TI  - Origin of the trochophora larva.
AB  - The trochophora larva, which is so well known from the marine plankton, is
      central to our understanding of the evolution of a large branch of the
      bilaterians. Two theories for this larval type have been prevalent, the trochaea
      theory and the theory proposed by Ivanova-Kazas. The embryology, or more
      precisely the cell-lineage, of these larvae seems to be central for our
      understanding of their origin, but important details have been missing. According
      to the trochaea theory, a circumblastoporal ring of blastomeres differentiates to
      follow the convoluted shape of the conspicuous ciliary bands of the larvae, with
      prototroch and metatroch around the mouth, forming a filtering system, and
      telotroch around the anus. According to the Ivanova-Kazas theory, the blastomeres
      with the ciliary bands develop through specialization of rings of cells of the
      general ciliation in a lecithotrophic larva. Now, a new cell-lineage study of the
      gastropod Crepidula has shown that the ring of cells at the edge of the
      blastopore develops into the band of cells carrying prototroch and metatroch,
      characteristic of the trochophora. This gives strong support to the trochaea
      theory.

PMID- 30109066
TI  - Formulation of chelating agent with surfactant in cloud point extraction of
      methylphenol in water.
AB  - Cloud point extraction (CPE) is a separation and preconcentration of non-ionic
      surfactant from one liquid phase to another. In this study, Sylgard 309 and three
      different types of additives for CPE, namely CPE-Sylgard, CPE-Sylgard-BMIMBr and
      CPE-Sylgard-GLDA, are investigated to extract methylphenol from water samples.
      The methylphenols are well separated by reversed-phase high-performance liquid
      chromatography (HPLC) with isocratic elution of acetonitrile : water; 60 : 40
      (v/v) and detection at 260 nm. The optimized parameters for the effect of salt,
      surfactant, temperature, time of extraction, pH, interference study and the
      performance of different additives on methylphenol extraction are investigated.
      CPE-Sylgard-GLDA is chosen because it gives us a high peak and good peak area
      compared with CPE-Sylgard and CPE-Sylgard-BMIMBr. The recovery extractions of CPE
      Sylgard-GLDA are obtained in the range of 80-99% as the percentage of relative
      standard deviation (RSD) is less than 10. The LOD and LOQ are 0.05 ppm and 0.18
      ppm, respectively. The method developed for CPE-Sylgard-GLDA coupled with HPLC is
      feasible for the determination of methylphenol because it is simple, effective,
      cheap, and produces a high percentage of recovery.

PMID- 30109067
TI  - Bayesian inference of antigenic and non-antigenic variables from
      haemagglutination inhibition assays for influenza surveillance.
AB  - Haemagglutination inhibition (HI) assays are typically used for comparing and
      characterizing influenza viruses. Data obtained from the assays (titres) are used
      quantitatively to determine antigenic differences between influenza strains.
      However, the use of these titres has been criticized as they sometimes fail to
      capture accurate antigenic differences between strains. Our previous analytical
      work revealed how antigenic and non-antigenic variables contribute to the titres.
      Building on this previous work, we have developed a Bayesian method for
      decoupling antigenic and non-antigenic contributions to the titres in this paper.
      We apply this method to a compendium of HI titres of influenza A (H3N2) viruses
      curated from 1968 to 2016. Remarkably, the results of this fit indicate that the
      non-antigenic variable, which is inversely correlated with viral avidity for the
      red blood cells used in HI assays, oscillates during the course of influenza
      virus evolution, with a period that corresponds roughly to the timescale on which
      antigenic variants replace each other. Together, the results suggest that the new
      Bayesian method is applicable to the analysis of long-term dynamics of both
      antigenic and non-antigenic properties of influenza virus.

PMID- 30109069
TI  - Effect of high-frequency electric field on the tissue sticking of minimally
      invasive electrosurgical devices.
AB  - Generally minimally invasive surgery is performed using an endoscope and other
      instruments including electrosurgical units (ESUs), and the adhesion of tissue to
      electrodes is a major concern. The mechanism governing this tissue sticking,
      especially the influence of high-frequency electric field, is still unclear. In
      this study, the effect of high-frequency electric field on the tissue sticking
      upon electrodes was investigated. The electrosurgical cutting test was performed
      on ex vivo fresh porcine liver under blend mode using a monopolar ESU. A heat
      adherence test without electric field was used as a control. For the control
      group, the electrode was heated and maintained at a certain temperature and
      directly in contact with porcine liver. Both sticking tissues obtained from these
      two tests are partially carbonized porcine liver tissue, but their microstructure
      and bonding with electrode are obviously different. The sticking tissue formed
      just under heat is composed of biggish nanoparticles of different sizes which are
      loosely aggregated and has a weak bonding with the electrode, while the sticking
      tissue from the electrosurgical cutting test consists of tightly packed fine
      nanoparticles of equable size as a result of thermo-electric coupling and has a
      strong bonding with the electrode. Obviously, high-frequency electric field plays
      an extremely important role in the formation of the sticking tissue. It is the
      thermo-electric coupling that underlies the function of minimally invasive
      electrosurgical devices, and the effect of high-frequency electric field cannot
      be ignored in the tissue sticking study and anti-sticking strategies.

PMID- 30109068
TI  - Population dynamics of synthetic terraformation motifs.
AB  - Ecosystems are complex systems, currently experiencing several threats associated
      with global warming, intensive exploitation and human-driven habitat degradation.
      Because of a general presence of multiple stable states, including states
      involving population extinction, and due to the intrinsic nonlinearities
      associated with feedback loops, collapse in ecosystems could occur in a
      catastrophic manner. It has been recently suggested that a potential path to
      prevent or modify the outcome of these transitions would involve designing
      synthetic organisms and synthetic ecological interactions that could push these
      endangered systems out of the critical boundaries. In this paper, we investigate
      the dynamics of the simplest mathematical models associated with four classes of
      ecological engineering designs, named Terraformation motifs (TMs). These TMs put
      in a nutshell different ecological strategies. In this context, some fundamental
      types of bifurcations pervade the systems' dynamics. Mutualistic interactions can
      enhance persistence of the systems by means of saddle-node bifurcations. The
      models without cooperative interactions show that ecosystems achieve restoration
      through transcritical bifurcations. Thus, our analysis of the models allows us to
      define the stability conditions and parameter domains where these TMs must work.

PMID- 30109071
TI  - Digital trade coin: towards a more stable digital currency.
AB  - We study the evolution of ideas related to creation of asset-backed currencies
      over the last 200 years and argue that recent developments related to distributed
      ledger technologies and blockchains give asset-backed currencies a new lease of
      life. We propose a practical mechanism combining novel technological
      breakthroughs with well-established hedging techniques for building an asset
      backed transactional oriented cryptocurrency, which we call the digital trade
      coin (DTC). We show that in its mature state, the DTC can serve as a much-needed
      counterpoint to fiat reserve currencies of today.

PMID- 30109070
TI  - Separation of the main flavonoids and essential oil from seabuckthorn leaves by
      ultrasonic/microwave-assisted simultaneous distillation extraction.
AB  - Volatile essential oils (EOs), non-volatile rutin (RU), quercetin (QU),
      kaempferol (KA) and isorhamnetin (IS) were effectively extracted and isolated
      from seabuckthorn (Hippophae rhamnoides L.) leaves by ionic liquid-based
      ultrasound/microwave-assisted simultaneous distillation extraction (ILUMASDE).
      After optimization by response surface methodology, EOs, RU, QU, KA and IS were
      separated under the following optimum conditions: an ionic liquid of 1.0 M 1
      butyl-3-methyl imidazole bromine salt ([C4mim]), liquid/solid ratio of 12 ml g-1,
      extraction time of 34 min, microwave power of 540 W and a fixed ultrasonic power
      of 50 W. Under the optimized conditions of ILUMASDE, the extraction yields of RU,
      QU, KA, IS and EOs were 9.18 +/- 0.35, 5.52 +/- 0.23, 3.03 +/- 0.11, 5.64 +/-
      0.24 mg g-1 and 0.095 +/- 0.004%, respectively. The yield of EOs obtained using
      ILUMASDE was 1.07-fold higher than that obtained by conventional
      hydrodistillation extraction (HDE). In addition, the components of the EOs
      obtained using ILUMASDE and HDE were similar. The extraction yields of RU, QU,
      KA, IS obtained by ILUMASDE were 1.03-1.35-fold higher than that obtained by the
      ethanol ultrasonic-assisted extraction (EUAE), ionic liquid-based ultrasonic
      assisted extraction (ILUAE) and ionic liquid-based microwave-assisted extraction
      (ILMAE). And the extraction time used by ILUMASDE was 34 min, which is 14.17%,
      56.67%, 56.67% and 85.00% less than those used by HDE, EUAE, ILUAE and ILMAE,
      respectively. Therefore, ILUMASDE can be considered a rapid and efficient method
      for extracting flavonoids and EO from seabuckthorn (Hippophae rhamnoids L.)
      leaves.

PMID- 30109073
TI  - Walking together: behavioural signatures of psychological crowds.
AB  - Research in crowd psychology has demonstrated key differences between the
      behaviour of physical crowds where members are in the same place at the same
      time, and the collective behaviour of psychological crowds where the entire crowd
      perceive themselves to be part of the same group through a shared social
      identity. As yet, no research has investigated the behavioural effects that a
      shared social identity has on crowd movement at a pedestrian level. To
      investigate the direction and extent to which social identity influences the
      movement of crowds, 280 trajectories were tracked as participants walked in one
      of two conditions: (1) a psychological crowd primed to share a social identity;
      (2) a naturally occurring physical crowd. Behaviour was compared both within and
      between the conditions. In comparison to the physical crowd, members of the
      psychological crowd (i) walked slower, (ii) walked further, and (iii) maintained
      closer proximity. In addition, pedestrians who had to manoeuvre around the
      psychological crowd behaved differently to pedestrians who had to manoeuvre past
      the naturally occurring crowd. We conclude that the behavioural differences
      between physical and psychological crowds must be taken into account when
      considering crowd behaviour in event safety management and computer models of
      crowds.

PMID- 30109072
TI  - Site-specific structural order in Alzheimer's Abeta42 fibrils.
AB  - Deposition of amyloid fibrils is a pathological hallmark of Alzheimer's disease.
      Abeta42 is the major protein whose aggregation leads to the formation of these
      fibrils. Understanding the detailed structure of Abeta42 fibrils is of particular
      importance for delineating the mechanism of Abeta42 aggregation and developing
      specific amyloid-targeting drugs. Here, we use site-directed spin labelling and
      electron paramagnetic resonance spectroscopy to study the site-specific
      structural order at each and every residue position in Abeta42 fibrils. Strong
      interactions between spin labels indicate highly ordered protein backbone at the
      labelling site, while weak interactions suggest disordered local structure. Our
      results show that Abeta42 consists of five beta-strands (residues 2-7, 10-13, 17
      20, 31-36, 39-41), three turns (residues 7-8, 14-16, 37-38) and one ordered loop
      (residues 21-30). Spin labels introduced at beta-strand sites show strong spin
      spin interactions, while spin labels at turn or loop sites show weak
      interactions. However, residues 24, 25 and 28 also show strong interactions
      between spin labels, suggesting that the loop 21-30 is partly ordered. In the
      context of recent structural work using solid-state NMR and cryoEM, the site
      specific structural order revealed in this study provides a different perspective
      on backbone and side chain dynamics of Abeta42 fibrils.

PMID- 30109074
TI  - Ligand-based pharmacophore model for the discovery of novel CXCR2 antagonists as
      anti-cancer metastatic agents.
AB  - Metastatic cancer is considered a fatal progression of cancer worldwide. It has
      been shown that a key player in this scenario is the CXC chemokine receptor 2
      (CXCR2). To identify novel CXCR2 antagonists, a pharmacophore model was built
      with the HipHop program by screening a database containing compounds which were
      designed based on the known structure-activity relationship (SAR) of the
      diarylurea series CXCR2 antagonists. Compound 1a bearing the novel skeleton was
      selected from database screening and subjected to the in vitro biological test
      which showed a moderate CXCR2 antagonist potential. With further modification and
      exploration of SAR, compound 1e demonstrated improved CXCR2 antagonist activity
      with an IC50 value of 14.8 uM. Furthermore, wound healing assay using the NCI
      H1299 cell line indicated that 1e showed an excellent anti-cancer metastatic
      effect (72% inhibition in cell migration at 50 ug ml-1).

PMID- 30109076
TI  - Safety assessment of petrochemical enterprise using the cloud model, PHA-LOPA and
      the bow-tie model.
AB  - Safe production is the foundation of the normal operations of petrochemical
      enterprises, and it helps maintain social stability. The main purpose of this
      study is to prevent petrochemical enterprise accidents by proposing a composite
      safety assessment approach based on the cloud model, preliminary hazard analysis
      layer of protection analysis (PHA-LOPA) and the bow-tie model. First, the
      petrochemical enterprise and its relevant indicators were evaluated based on the
      cloud model. Second, the quantitative effect of the uncertainty transformation on
      the evaluation result of the cloud model was further analysed. This mainly
      includes the error analysis of the numerical characteristics under the conditions
      of few samples and small values. Third, the critical indicators such as shock and
      noise can be weakened and prevented by corresponding safety measures based on PHA
      LOPA and the bow-tie model. After adopting two independent protection layers, the
      risk levels of shock and noise decrease from 3 to 2. Then, shock and noise were
      analysed in depth with the bow-tie model, and the causes and consequences were
      identified. Moreover, corresponding safety measures were taken to prevent
      accidents. The case study validated the validity and feasibility of the composite
      safety assessment approach proposed here.

PMID- 30109075
TI  - Donor-acceptor Stenhouse adduct-grafted polycarbonate surfaces: selectivity of
      the reaction for secondary amine on surface.
AB  - Donor-acceptor Stenhouse adducts (DASAs) are gaining attention from organic and
      material chemists due to their visible light-stimulated photochromic properties.
      In this report, we present a facile method for grafting coloured triene on
      polycarbonate surface, without involving any pre-treatments like plasma
      activation, etc. The chemoselectivity of carbonate with a primary amine and
      Meldrum's activated furan (MAF) with polymer bound secondary amine has been
      exploited to graft photoswitchable DASA on the polymer surface. Primary,
      secondary and tertiary amine-functionalized polycarbonate surfaces have been
      prepared to evaluate the reactivity of amine with MAF.

PMID- 30109077
TI  - Process optimization of ultrasound-assisted treatment for soya bean protein
      isolate/polyacrylamide composite film.
AB  - In this paper, composite films composed of soya bean protein isolate (SPI) and
      polyacrylamide (PAM) were prepared under variations of ultrasonic power,
      treatment time and heating temperature. The effects of the major processing
      parameters related to ultrasonic-assisted treatment were evaluated and optimized
      through the single-factor analysis and Box-Behnken design (BBD), respectively,
      when the tensile strength of composite films was considered as the response
      value. The single-factor analysis was carried out to study the effects of
      ultrasonic power, treatment time and heating temperature on the viscosity and
      cohesion of the slurry and the tensile strength of SPI/PAM composite films, which
      also provided a reasonable data range of each factor for further optimization.
      Experiment results indicated that these three factors play a significant role in
      the tensile strength of films. Then BBD was applied to optimize the treatment
      conditions of these three factors, using the tensile strength of films as the
      response value. According to the interactive second-order polynomial model of
      three factors and the three-dimensional response surface, the maximum tensile
      strength of films was obtained under the optimal condition. To verify the
      reliability of the model, the experiment with the optimal condition was
      conducted, and results demonstrated that the observed tensile strength was in
      agreement with the predicated one. Also, the morphology and water solubility of
      the films showed that the film can be coated on the yarns evenly and removed
      clearly.

PMID- 30109078
TI  - Imaging of nuclear magnetic resonance spin-lattice relaxation activation energy
      in cartilage.
AB  - Samples of human and bovine cartilage have been examined using magnetic resonance
      imaging to determine the proton nuclear magnetic resonance spin-lattice
      relaxation time, T1, as a function of depth within through the cartilage tissue.
      T1 was measured at five to seven temperatures between 8 and 38 degrees C. From
      this, it is shown that the T1 relaxation time is well described by Arrhenius-type
      behaviour and the activation energy of the relaxation process is quantified. The
      activation energy within the cartilage is approximately 11 +/- 2 kJ mol-1 with
      this notably being less than that for both pure water (16.6 +/- 0.4 kJ mol-1) and
      the phosphate-buffered solution in which the cartilage was immersed (14.7 +/- 1.0
      kJ mol-1). It is shown that this activation energy increases as a function of
      depth in the cartilage. It is known that cartilage composition varies with depth,
      and hence, these results have been interpreted in terms of the structure within
      the cartilage tissue and the association of the water with the macromolecular
      constituents of the cartilage.

PMID- 30109079
TI  - The impact of nutritional quality and gut bacteria on the fitness of Bactrocera
      minax (Diptera: Tephritidae).
AB  - To examine how nutritional quality and resident gut bacteria interplay in
      improving the fitness of an oligophagous fruit fly, Bactrocera minax, artificial
      sucrose diets and full diets (sucrose, tryptone and yeast extract) were fed to
      flies with and without antibiotic supplementation. Furthermore, Klebsiella
      oxytoca and Citrobacter freundii were supplemented to sucrose-only diets. Flies
      were maintained in the laboratory and the fitness parameters, male and female
      longevity, number of copulations and female fecundity, were recorded. Full diet
      without bacterial depletion significantly increased fecundity and copulation. In
      the absence of gut bacteria, flies fed with full diets had significantly
      decreased mean fecundity and copulation rate. Flies that were fed with sucrose
      diet had a very low copulation rate and produced no eggs. Diet type and the
      presence of bacteria did not have any effect on the average longevity of male and
      female flies. Bacterial supplementation in sucrose diets did not improve any of
      the measured parameters. The results demonstrate that gut bacteria interact with
      diet to influence mating and reproduction in B. minax. Symbiotic bacteria
      significantly and positively impact reproduction in B. minax; however, their
      impact can only be fully realized when the flies are fed with a nutritionally
      complete diet.

PMID- 30109080
TI  - A rapid microwave synthesis of green-emissive carbon dots with solid-state
      fluorescence and pH-sensitive properties.
AB  - The emerging carbon quantum dots (CQDs) have been attracting significant
      attention for their prominent fluorescence, excellent stability and outstanding
      biocompatibility. Here, we report a facile one-step synthesis of highly
      fluorescent CQDs by using phthalic acid and triethylenediamine hexahydrate as
      precursors through a simple microwave-assisted method. The reaction time needed
      is only 60 s, which is less time-consuming than most previous reports. The
      phthalic acid with a benzene ring can improve the photoluminescence properties of
      CQDs as it can provide foreign sp2 conjugating units, and then finally result in
      long-wavelength emission. The synthesized CQDs were fully characterized by
      transmission electron microscopy, X-ray photoelectron spectroscopy and Fourier
      transform infrared spectroscopy. Besides, the impacts of different freed ratio on
      physical and chemical properties of CQDs were investigated in detail. The
      prepared CQDs exhibited strong green fluorescence with a broad maximum emission
      wavelength. The quantum yields of the CQDs can reach 16.1% in aqueous solution
      and they were successfully used in cell imaging with good biocompatibility.
      Moreover, in solid state, the CQDs with the feed ratio of 1 : 0.5 showed a strong
      green-yellow fluorescence which may have great potential to fabricate
      optoelectronic devices. Furthermore, the prepared CQDs also showed high pH
      sensitivity and can act as a fluorescence nanosensor for pH sensing.

PMID- 30109081
TI  - Illuminating gillnets to save seabirds and the potential for multi-taxa bycatch
      mitigation.
AB  - Bycatch in net fisheries is recognized as a major source of mortality for many
      marine species, including seabirds. Few mitigation solutions, however, have been
      identified. We assessed the effectiveness of illuminating fishing nets with green
      light emitting diodes (LEDs) to reduce the incidental capture of seabirds.
      Experiments were conducted in the demersal, set gillnet fishery of Constante,
      Peru and compared 114 pairs of control and illuminated nets. We observed captures
      of a total of 45 guanay cormorants (Phalacrocorax bougainvillii), with 39 caught
      in control nets and six caught in illuminated nets. Seabird bycatch in terms of
      catch-per-unit-effort was significantly (p < 0.05) higher in control nets than in
      illuminated nets, representing an 85.1% decline in the cormorant bycatch rate.
      This study, showing that net illumination reduces seabird bycatch and previous
      studies showing reductions in sea turtle bycatch without reducing target catch,
      indicates that net illumination can be an effective multi-taxa bycatch mitigation
      technique. This finding has broad implications for bycatch mitigation in net
      fisheries given LED technology's relatively low cost, the global ubiquity of net
      fisheries and the current paucity of bycatch mitigation solutions.

PMID- 30109082
TI  - Impact of soil contamination on the growth and shape of ant nests.
AB  - As entomopathogens are detrimental to the development or even survival of insect
      societies, ant colonies should avoid digging into a substrate that is
      contaminated by fungal spores. Here, we test the hypotheses that Myrmica rubra
      ant workers (i) detect and avoid fungus-infected substrates and (ii) excavate
      nest patterns that minimize their exposure to entomopathogenic spores. Small
      groups of M. rubra workers were allowed to dig their nest in a two-dimensional
      sand plate of which one half of the substrate contained fungal spores of
      Metarhizium brunneum, while the other half was spore-free. We found that the
      overall digging dynamics of M. rubra nests was not altered by the presence of
      fungus spores. By contrast, the shape of the excavated areas markedly differed:
      control nests showed rather isotropic patterns, whereas nests that were partially
      dug into a fungus-contaminated substrate markedly deviated from a circular shape.
      This demonstrates that the sanitary risks associated with a digging substrate are
      key factors in nest morphogenesis. We also found that M. rubra colonies were able
      to discriminate between the two substrates (fungus-infected or not). Furthermore,
      some colonies unexpectedly showed a high consistency in excavating mainly the
      infected substrate. This seemingly suboptimal preference for a contaminated soil
      suggests that non-lethal doses of fungal spores could help ant colonies to
      trigger 'immune priming'. The presence of fungi may also indicate favourable
      ecological conditions, such as humid and humus-rich soil, that ants use as a cue
      for selecting suitable nesting sites.

PMID- 30109083
TI  - Antioxidant and angiotensin I-converting enzyme inhibitory activities of Xuanwei
      ham before and after cooking and in vitro simulated gastrointestinal digestion.
AB  - Xuanwei ham is especially rich in a large amount of peptides and free amino acids
      under the action of protein degradation. Some of these peptides can potentially
      exert bioactivities of interest for human health. Traditionally, Xuanwei ham
      should undergo Chinese household cooking treatments before eating. However, it
      has not been known how its bioactivity changes after cooking and gastrointestinal
      digestion. Herein, Xuanwei ham is analysed before and after cooking, as well as
      gastrointestinal digestion being simulated so as to evaluate and compare its
      effect on antioxidant and angiotensin I-converting enzyme (ACE) inhibitory
      activities. The antioxidant activity is analysed using five different methods,
      and results demonstrate that cooking has some negative effects on antioxidative
      capacity when determined using different antioxidant methods except for a
      significant increment in 1,1'-diphenyl-2-picrylhydrazyl radical-scavenging
      activity, while ACE inhibitory activity increases significantly after cooking
      compared with control samples. After gastrointestinal digestion of samples, there
      is a significant increment of the antioxidant and ACE inhibitory activities in
      comparison with control and cooked samples. Particularly, after gastrointestinal
      digestion, free thiols content and 2,2'-azino-bis(3-ethylbenzothiazoline-6
      sulfonic acid) radical-cation-scavenging activity of Xuanwei ham, respectively,
      increase about twice and fourfold, while ACE inhibitory activity increases about
      twice compared to cooked samples, reaching the value of 83.73%. Therefore,
      through cooking the antioxidant activity and ACE inhibitory activity of Xuanwei
      ham are not completely lost and a part of them is still maintained, while
      gastrointestinal digestion produces a significant enhancement in both
      bioactivities, highlighting a greater potential for a beneficial physiological
      effect on human health after eating it.

PMID- 30109085
TI  - Finite-element analysis of microwave scattering from a three-dimensional human
      head model for brain stroke detection.
AB  - In this paper, a detailed analysis of microwave (MW) scattering from a three
      dimensional (3D) anthropomorphic human head model is presented. It is the first
      time that the finite-element method (FEM) has been deployed to study the MW
      scattering phenomenon of a 3D realistic head model for brain stroke detection. A
      major contribution of this paper is to add anatomically more realistic details to
      the human head model compared with the literature available to date. Using the
      MRI database, a 3D numerical head model was developed and segmented into 21
      different types through a novel tissue-mapping scheme and a mixed-model approach.
      The heterogeneous and frequency-dispersive dielectric properties were assigned to
      brain tissues using the same mapping technique. To mimic the simulation set-up,
      an eight-elements antenna array around the head model was designed using dipole
      antennae. Two types of brain stroke (haemorrhagic and ischaemic) at various
      locations inside the head model were then analysed for possible detection and
      classification. The transmitted and backscattered signals were calculated by
      finding out the solution of the Helmholtz wave equation in the frequency domain
      using the FEM. FE mesh convergence analysis for electric field values and
      comparison between different types of iterative solver were also performed to
      obtain error-free results in minimal computational time. At the end, specific
      absorption rate analysis was conducted to examine the ionization effects of MW
      signals to a 3D human head model. Through computer simulations, it is foreseen
      that MW imaging may efficiently be exploited to locate and differentiate two
      types of brain stroke by detecting abnormal tissues' dielectric properties. A
      significant contrast between electric field values of the normal and stroke
      affected brain tissues was observed at the stroke location. This is a step
      towards generating MW scattering information for the development of an efficient
      image reconstruction algorithm.

PMID- 30109084
TI  - Nanostructured carbon black for simultaneous electrochemical determination of
      trace lead and cadmium by differential pulse stripping voltammetry.
AB  - Nanostructured carbon black (CB) was first employed directly in this paper for
      the simultaneous electrochemical determination of trace Pb(II) and Cd(II) using
      differential pulse anodic stripping voltammetry. The morphology and surface
      properties of conductive CB were characterized by transmission electron
      microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, ultraviolet
      visible spectroscopy and Raman spectroscopy. Special pore structures, as well as
      surface chemical functional groups, endow CB with excellent catalytic and
      adsorption properties. Some parameters affecting electrical analysis performance
      were investigated systematically including deposition time and potential, pH
      value of solution, volume of suspension, amount of Bi(III) and Nafion solution.
      CB-Nafion-glassy carbon electrode sensor linear response ranges from 6 to 1000 nM
      for selective and simultaneous determination. The detection limits were
      calculated to be 8 nM (0.9 ug l-1) for Cd(II) and 5 nM (1.0 ug l-1) for Pb(II)
      (S/N = 3) for the electrocatalytic determination under optimized conditions. The
      method was successfully used to the determination of actual samples and good
      recovery was achieved from different spiked samples. Low detection limits and
      good stability of the modified electrode demonstrated a promising perspective for
      the detection of trace metal ions in practical application.

PMID- 30109087
TI  - Comparison of electron injection and recombination on TiO2 nanoparticles and ZnO
      nanorods photosensitized by phthalocyanine.
AB  - Titanium dioxide (TiO2) and zinc oxide (ZnO) semiconductors have similar band gap
      positions but TiO2 performs better as an anode material in dye-sensitized solar
      cell applications. We compared two electrodes made of TiO2 nanoparticles and ZnO
      nanorods sensitized by an aggregation-protected phthalocyanine derivative using
      ultrafast transient absorption spectroscopy. In agreement with previous studies,
      the primary electron injection is two times faster on TiO2, but contrary to the
      previous results the charge recombination is slower on ZnO. The latter could be
      due to morphology differences and the ability of the injected electrons to travel
      much further from the sensitizer cation in ZnO nanorods.

PMID- 30109086
TI  - Primary biocompatibility tests of poly(lactide-co-glycolide)-(poly-L
      orithine/fucoidan) core-shell nanocarriers.
AB  - Layer-by-layer (LbL) self-assembly is the technology used in intermolecular
      static electricity, hydrogen bonds, covalent bonds and other polymer interactions
      during film assembling. This technology has been widely studied in the drug
      carrier field. Given their use in drug delivery systems, the biocompatibility of
      these potential compounds should be addressed. In this work, the primary
      biocompatibility of poly(lactide-co-glycolide)-(poly-L-orithine/fucoidan) [PLGA
      (PLO/fucoidan)] core-shell nanoparticles (NPs) was investigated. Atomic force
      microscopy revealed the PLGA-(PLO/Fucoidan)4 NPs to be spherical, with a uniform
      size distribution and a smooth surface, and the NPs were stable in physiological
      saline. The residual amount of methylene chloride was further determined by
      headspace gas chromatography, in which the organic solvent can be volatilized
      during preparation. Furthermore, cell viability, acridine orange/ethidium bromide
      staining, haemolysis and mouse systemic toxicity were all assessed to show that
      PLGA-(PLO/fucoidan)4 NPs were biocompatible with cells and mice. Therefore, these
      NPs are expected to have potential applications in future drug delivery systems.

PMID- 30109089
TI  - A porphyrin-centred fullerene tetramer containing an N@C60 substituent.
AB  - An N@C60-containing C60 tetramer was synthesized by quadruple 1,3-dipolar
      cycloaddition (Prato) reaction. This molecule demonstrates the N@C60 qubit's
      ability to form covalently linked arrays. Furthermore, it provides a promising
      scaffold with which to measure multiple qubit-qubit interactions; which must be
      well characterized for a functioning quantum information processing architecture.

PMID- 30109088
TI  - Structure of [60]fullerene with a mobile lithium cation inside.
AB  - The structure of crystalline [60]fullerene with a lithium cation inside (Li+@C60)
      was determined by synchrotron radiation X-ray diffraction measurements to
      understand the electrostatic and thermal properties of the encapsulated Li+
      cation. Although the C60 cages show severe orientation disorder in [Li+@C60](TFPB
      ).C4H10O and [Li+@C60](TFSI-).CH2Cl2, the Li+ cations are rather ordered at
      specific positions by electrostatic interactions with coordinated anions outside
      the C60 cage. The Li+@C60 molecules in [Li+@C60](ClO4-) with a rock-salt-type
      cubic structure are fully disordered with almost uniform spherical shell charge
      densities even at 100 K by octahedral coordination of ClO4- tetrahedra and show
      no orientation ordering, unlike [Li+@C60](PF6-) and pristine C60. Single-bonded
      (Li+@C60-)2 dimers in [Li+@C60-](NiOEP)?CH2Cl2 are thermally stable even at 400 K
      and form Li+-C bonds which are shorter than Li+-C bonds in [Li+@C60](PF6-) and
      suppress the rotational motion of the Li+ cations.

PMID- 30109090
TI  - Rheological properties and damage-control mechanism of oil-based drilling fluid
      with different types of weighting agents.
AB  - The great amount of solid particles contained in a weighting agent is a major
      cause of the problems in both rheology properties and damage control mechanism of
      an oil-based drilling fluid (OBM). Therefore, a proper type of weighting agent
      can be a solution for the application of OBM. In this study, three weighting
      agents that have been commonly used with OBM, namely, standard barite, submicron
      barite and superfine manganese ore, are studied. Rheological properties of OBM
      and the degree of formation damage are assessed with regard to the three
      weighting agents. The agents are also studied in aspects of particle size,
      micromorphology, filtration loss and wall-building property, acid dissolution
      efficiency of mud cake, lubricity and sedimentation stability to analyse the
      effects of the agents on rheological properties and the degree of damage as well
      as to figure out the mechanism of rheology control and damage control. For the
      OBM, there is a mutual effect between rheological stability and the degree of
      damage. In consideration of the agents' properties, we can enhance the
      rheological stability of the OBM and control the degree of formation damage by
      properly selecting particle size, using acid-soluble materials and forming the
      mud cake with ultra-low permeability that can easily be cleared away.

PMID- 30109091
TI  - N,N-chelated nickel catalysts for highly branched polyolefin elastomers: a
      survey.
AB  - The physical properties and end applications of polyolefin materials are defined
      by their chain architectures and topologies. These properties can, in part, be
      controlled by a judicious choice of the steric and electronic properties of the
      catalyst and, in particular, the ligand framework. One major achievement in this
      field is the discovery of thermoplastic polyolefin elastomers that combine the
      processing and recyclable characteristics of thermoplastics with the flexibility
      and ductility of elastomers. These polymers are highly sought after as
      alternative materials to thermoset elastomers. In this perspective, works in the
      literature related to the development of nickel catalysts as well as their
      implementations for the synthesis of polyolefin elastomers are summarized in
      detail. Throughout the perspective, attention has been focused on developing the
      relationship between catalyst structure and performance, on strategies for the
      synthesis of polyolefin elastomer using nickel catalysts, on properties of the
      resultant polyolefin, such as degree of branching and crystallinity, as well as
      on their effects on mechanical properties. The future perspective regarding the
      most recent developments in single-step production of polyethylene elastomers
      will also be presented.

PMID- 30109093
TI  - High-density polyethylene crystals with double melting peaks induced by ultra
      high-molecular-weight polyethylene fibre.
AB  - High-density polyethylene (HDPE)/ultra-high-molecular-weight polyethylene
      (UHMWPE) fibre composites were prepared via solution crystallization to
      investigate the components of epitaxial crystal growth on a highly oriented
      substrate. Scanning electron microscopy morphologies of HDPE crystals on UHMWPE
      fibres revealed that the edge-on ribbon pattern crystals that were formed
      initially on UHMWPE fibres converted afterwards to a sheet shape as
      crystallization progressed. Wide-angle X-ray diffraction confirmed that the
      polymer chain oriented along the fibre axis and the orthorhombic crystal form of
      HDPE remained unchanged in HDPE/UHMWPE fibre composite systems. The thermal
      behaviour of the fibre composites measured by differential scanning calorimetry
      showed double melting peaks, the nature of which, as disclosed by partial melting
      experiments, is ascribed to bilayer components existing in the induced crystals:
      the inner layer is composed of more regularly folded chain crystals induced by
      UHMWPE fibres, and the outer layer formed on the inner one with a thinner and
      lower ordered crystal structure.

PMID- 30109092
TI  - Social behaviour in bees influences the abundance of Sodalis (Enterobacteriaceae)
      symbionts.
AB  - Social interactions can facilitate transmission of microbes between individuals,
      reducing variation in gut communities within social groups. Thus, the evolution
      of social behaviours and symbiont community composition have the potential to be
      tightly linked. We explored this connection by characterizing the diversity of
      bacteria associated with both eusocial and solitary bee species within the
      behaviourally variable family Halictidae using 16S amplicon sequencing. Contrary
      to expectations, we found few differences in bacterial abundance or variation
      between social forms; most halictid species appear to share similar gut bacterial
      communities. However, several strains of Sodalis, a genus described as a symbiont
      in a variety of insects but yet to be characterized in bees, differ in abundance
      between eusocial and solitary bees. Phylogenetic reconstructions based on whole
      genome alignments indicate that Sodalis has independently colonized halictids at
      least three times. These strains appear to be mutually exclusive within
      individual bees, although they are not host-species-specific and no signatures of
      vertical transmission were observed, suggesting that Sodalis strains compete for
      access to hosts. The symbiosis between halictids and Sodalis therefore appears to
      be in its early stages.

PMID- 30109095
TI  - Cavitating flow-induced unsteady pressure pulsations in a low specific speed
      centrifugal pump.
AB  - With the development of cavitation, the high-energy pressure wave from a
      cavitation bubble collapsing is detrimental to the stable operation of
      centrifugal pumps. The present paper concentrates on pressure pulsations under
      cavitation conditions, and pressure amplitudes at the blade-passing frequency
      (fBPF) and RMS values in the 0-500 Hz frequency band are combined to investigate
      cavitation-induced pressure pulsations. The results show that components at fBPF
      always dominate the pressure spectrum even at the full cavitation stage. For
      points P1-P7 on the volute side wall, with a decreasing cavitation number, the
      pressure energy first remains unchanged and then it rises rapidly after the
      critical point. For point In1 in a volute suction pipe located close to the
      cavitation region, the pressure energy changes slightly at high cavitation
      numbers; then for a particular cavitation number range, the pressure energy
      decreases, and finally increases again. For different flow rates, the pressure
      energy at the critical point is much lower than the initial amplitude at the non
      cavitation condition for In1. This demonstrates that the cavitation cloud in the
      typical stage is partially compressible, and the emitted pressure wave from a
      collapsing cavitation bubble is absorbed and attenuated significantly. Finally,
      this leads to the pressure energy decreasing rapidly for the measuring point In1
      near the cavitation region.

PMID- 30109094
TI  - Corrosion-resistant systems of formate packer fluid for G3/N80/TP110SS pipes at
      high temperature, high pressure and high H2S/CO2 ratios.
AB  - A series of corrosion problems caused by high-temperature, high-pressure and high
      acid gas environments has been an issue in oil and gas production for a long
      time. During the development of a high-acid gas field, the petroleum pipe is
      subjected to many aspects of corrosion, and the corrosion mechanism is
      complicated by the condition of the coexistence of H2S/CO2. Based on the study of
      the corrosion problem associated with the formate packer fluid in Southwest
      China, three kinds of steels were studied for corrosion prevention in the alloy
      G3/N80 steel/TP110SS steel. The study shows that the corrosion rate of the
      formate packer fluid is low, but corrosion is severe in environments
      characterized by high temperatures, high pressures and high-acid gas contents.
      Based on the consideration of cost and the difficulty of realization, an anti
      corrosion system was constructed based on the existing packer fluid, mainly
      through the introduction of a variety of anti-corrosion additives. Through the
      selection of various additives and corrosion experiments, a corrosion protection
      system of formate packer fluid was developed. Corrosion tests show that the
      corrosion rate of the system must be less than 0.076 mm yr-1 to achieve the
      purpose of corrosion protection. The formate packer fluid with corrosion
      protection can meet the needs of the current application.

PMID- 30109096
TI  - Identification and characterization of circular RNAs in Qinchuan cattle testis.
AB  - Circular RNA (circRNA) is a new class of non-coding RNA that has recently
      attracted researchers' interest. Studies have demonstrated that circRNA can
      function as microRNA sponges or competing endogenous RNAs. Although circRNA has
      been explored in some species and tissues, the genetic basis of testis
      development and spermatogenesis in cattle remains unknown. We performed ribo
      depleted total RNA-Seq to detect circRNA expression profiles of neonatal (one
      week old) and adult (4 years old) Qinchuan cattle testes. We obtained 91 112 596
      and 80 485 868 clean reads and detected 21 753 circRNAs. A total of 4248 circRNAs
      were significantly differentially expressed between neonatal and adult cattle
      testes. Among these circRNAs, 2225 were upregulated, and 2023 were downregulated
      in adult cattle testis. Genomic feature, length distribution and other
      characteristics of the circRNAs in cattle testis were studied. Moreover, Gene
      Ontology and KEGG pathway analyses were performed for source genes of circRNAs.
      These source genes were mainly involved in tight junction, adherens junction,
      TGFbeta signalling pathway and reproduction, such as PIWIL1, DPY19L2, SLC26A8,
      IFT81, SMC1B, IQCG and TTLL5. CircRNA expression patterns were validated by RT
      qPCR. Our discoveries provide a solid foundation for the identification and
      characterization of key circRNAs involved in testis development or
      spermatogenesis.

PMID- 30109097
TI  - Unexpected formation of polymeric silver(I) complexes of azine-type ligand via
      self-assembly of Ag-salts with isatin oxamohydrazide.
AB  - Isatin oxamohydrazide (L) reacted with the aqueous solution of silver nitrate at
      room temperature afforded the polymeric silver(I) nitrato complex, [Ag2L'(NO3)2]
      n , (1) of the azine ligand (L'). Similarly, the reaction of L with silver(I)
      perchlorate gave the [Ag2L'2(ClO4)2] n , (2) coordination polymer. Careful
      inspection of the crystals from the nitrato complex preparation showed the
      presence of another crystalline product which is found to be [Ag(Isatin-3
      hydrazone)NO3], (3) suggesting that the reaction between silver(I) nitrate and L
      proceeds first by the hydrolysis of L to the isatin hydrazone which attacks
      another molecule of L to afford L'. Testing metal salts such as Ni2+, Co2+, Mn2+,
      Cu2+ and Cd2+ did not undergo any reaction with L either under the same reaction
      conditions or with heating under reflux up to 24 h. Treatment of the warm
      alcoholic solution of L with few drops of 1 : 1 (v/v) hydrochloric acid gave the
      free ligand (L') in good yield. The [Ag2L'(NO3)2] n complex forms a two
      dimensional infinite coordination polymer, while the [Ag2L'2(ClO4)2] n forms one
      dimensional infinite chains with an alternating silver-azine backbone.
      Quantitative analysis of the intermolecular interactions in their crystals is
      made using Hirshfeld surface analysis. Density functional theory studies were
      performed to investigate the coordination bonding in the studied complexes.

PMID- 30109099
TI  - Thermal effect on the compression coefficient of heavy oil reservoir rocks.
AB  - The ever-decreasing oil resources receive more and more attention for the
      exploration and development of heavy oil reservoirs. Owing to the high viscosity
      and poor fluidity of heavy oil, it is necessary to use the method of injecting
      high-temperature fluid in the development process. But, this will cause a
      significant increase in the temperature in oil reservoir, and thus the
      compression coefficient of reservoir rock has a greater impact. The compression
      coefficient of heavy oil reservoirs at different temperatures was tested. The
      results show that the compression coefficient of rock is closely related to the
      nature of rock itself and its stress and temperature environment: the compression
      coefficient increases with the increase in rock porosity; the compression
      coefficient decreases with the increase in the effective confining pressure and
      increases with the increase in temperature. When the temperature is low, the
      increase in the compression coefficient is larger. As the temperature increases,
      the increase in the compression coefficient tends to decrease gradually. Because
      the temperature of the reservoir is higher than that of the ground, the influence
      of the temperature on the reservoir compression coefficient should be taken into
      account when carrying out the production forecast.

PMID- 30109098
TI  - Mammalian chromosome-telomere length dynamics.
AB  - Individual chromosome arms have specific individual telomere lengths (TLs). Past
      studies within species have shown strong positive correlations between individual
      chromosome length and TL at that chromosome. While the reasons for these
      associations are unclear, the strength and consistency of the associations across
      disparate taxa suggest that this is important to telomere biology and should be
      explored further. If TL is primarily determined by chromosome length, then
      chromosome length should be considered and controlled for in cross-species
      analyses of TL. Here, we employ a cross-species approach to explore whether the
      chromosome length-TL association observed intraspecifically is a determinant of
      mean TL across species. Data were compiled from two studies characterizing TL
      across a range of mammalian taxa and analysed in a phylogenetic framework. We
      found no significant relationship between TL and chromosome size across mammals
      or within mammalians orders. The pattern trends in the expected direction and we
      suggest may be masked by evolutionary lag effects.

PMID- 30109100
TI  - Synthesis and structure/properties characterizations of four polyurethane model
      hard segments.
AB  - Four model polyurethane (PU) hard segments were synthesized by reaction of
      butanol with four typical diisocyanates. The four diisocyanates were aromatic
      4,4'-diphenylmethane diisocyanate (4,4'-MDI) and MDI-50 (50% mixture of 2,4'-MDI
      and 4,4'-MDI), cycloaliphatic 4,4'-dicyclohexylmethane diisocyanate (HMDI) and
      linear aliphatic 1,6-hexamethylene diisocyanate (HDI). FTIR, 1H NMR, 13C NMR, MS,
      X-ray and DSC methods were employed to determine their structures and to analyse
      their crystallization behaviours and hydrogen bonding interactions. Each of the
      four PU compounds prepared in the present work displays unique spectral
      characteristics. The FTIR bands and NMR resonance peaks assigned in the four
      samples thus provide a reliable database and starting point for investigating the
      relationship between hard segment structure and the crystallization and hydrogen
      bonding behaviour in more complex-segmented PU compositions.

PMID- 30109102
TI  - Aerofoil optimization for improving the power performance of a vertical axis wind
      turbine using multiple streamtube model and genetic algorithm.
AB  - This paper reports on the optimization of the NACA0015 aerofoil for improving the
      power performance of a vertical axis wind turbine (VAWT). The target range of the
      chord Re is 3 * 105-106, the tip speed ratio (TSR) is 2-6 and the solidity is 0.2
      0.6. This aerofoil is widely applied in small-scale VAWTs. In the optimization
      process, in which the class and shape function transformation parametrization
      method was used to perturb the aerofoil geometry, the thickness and camber of the
      aerofoil were selected as the constraints and the value of the maximum tangential
      force coefficient was chosen as the objective function. The aerodynamic
      performance of the aerofoil was calculated by combining the XFOIL program and
      Viterna-Corrigan post-stall model, while the aerofoil's performance was validated
      with computational fluid dynamic simulations. The results illustrated that,
      compared to an unoptimized NACA0015 aerofoil, the optimized aerofoil's lift to
      drag ratio was improved over a wide range of attack angles and the stall
      performance was gentler. The maximum lift coefficient, the maximum lift to drag
      ratio and the maximum tangential force coefficient were increased by 7.5%, 9% and
      8.87%, respectively. Finally, this paper predicted the rotor efficiency with both
      the unoptimized and optimized NACA0015 aerofoils for different TSRs and different
      solidities using the multiple streamtube model. The results showed that the rotor
      with the optimized aerofoil has a higher efficiency.

PMID- 30109101
TI  - Parental and offspring larval diets interact to influence life-history traits and
      infection with dengue virus in Aedes aegypti.
AB  - The environmental conditions experienced by parents can influence offspring
      phenotype along with the conditions experienced by offspring. These parental
      effects are clear in organisms that display parental care and are less clear in
      other organisms. Here, we consider effects of parental and offspring larval
      nutrition on offspring development time, survivorship and infection with dengue
      virus in Aedes aegypti, the mosquito vector of dengue, chikungunya, yellow fever
      and Zika. Parents were raised on either high or low larval detritus inputs with
      subsequent offspring being divided into two groups, one receiving high nutrients
      and the other low. Low nutrient females from low nutrient parents (LL) developed
      significantly slower than those from high nutrient parents (HL). Females from all
      parent by offspring nutrient treatment groups were equally likely to become
      infected with dengue virus at 24 h, 3 days and 14 days. After 14 days, high
      nutrient females from low nutrient parents (LH) had 11 times higher viral titres
      and more disseminated infections than high nutrient females from high nutrient
      parents (HH). These results suggest that carry-over environmental stress from the
      parental generation can influence life histories and arbovirus infection in Ae.
      aegypti females. We found males to be robust to the life-history parameters
      measured, suggesting sex-specific differences which may relate to their lower
      nutrient requirements for metamorphosis.

PMID- 30109103
TI  - Experimental study on permeability characteristics of gas-containing raw coal
      under different stress conditions.
AB  - The present experimental study on permeability characteristics for raw coal under
      different stress states is implemented by applying the triaxial self-made 'THM
      coupled with servo-controlled seepage apparatus for gas-containing coal'; the
      result indicates that the flow rate of gas in the coal sample gradually decreases
      with the nonlinear loading of axial pressure and increases with the nonlinear
      unloading of axial stress and confining pressure. The flow rate, axial stress and
      confining pressure curves all satisfy the negative exponential function relation.
      When the sample reaches the peak intensity, the sample will be destroyed and the
      stress will drop rapidly; then the flow rate of the sample will increase rapidly.
      At this stage, the flow rate and axial strain show an oblique 'v' pattern. The
      flow rate of the coal sample increases nonlinearly with the increase of gas
      pressure; the relation curve between flow rate and gas pressure satisfies the
      power function relation. Under the same confining pressure and gas pressure
      conditions, the larger the axial stress, the smaller the flow rate of the coal
      sample. Under the same axial stress and gas pressure conditions, the flow rate of
      the coal sample will first decrease, but then increase as the confining pressure
      decreases. During the post-peak loading and unloading process, the flow rate of
      the coal sample will decrease with the loading of confining pressure but increase
      with the unloading of confining pressure, and there will be an increase in wave
      shape with the increase in axial strain. The flow rate of each loading and
      unloading confining pressure is higher than that of the previous loading and
      unloading confining pressure. At the post-peak stage, the relation curve between
      the flow rate of the coal sample and the confining pressure satisfies the power
      function relation in the process of loading and unloading confining pressure.

PMID- 30109104
TI  - Reintroducing apex predators: the perils of muddling guilds and taxocenoses.

PMID- 30109105
TI  - Fabrication of superhydrophobic composite coating based on fluorosilicone resin
      and silica nanoparticles.
AB  - Composite superhydrophobic coating built with film former and filler is
      attracting much attention for its facile and convenient fabrication, but
      significant limitations and disadvantages still remain. In this paper, a
      composite superhydrophobic coating is introduced which can be cured at room
      temperature and made by dispersing modified silica nanoparticles with 1H, 1H, 2H,
      2H-perfluorooctyltriethoxysilane in fluorosilicone resin. Silica content and
      dispersion time showed obvious influences on the morphology and topography of
      composite coating by reuniting dispersed nanoparticles to form peaks on the
      surface. Excessively large distances between these peaks would decrease water
      contact angle value. Increasing slope of peaks, appropriate distance between
      peaks and decreasing diameter size of peaks would diminish sliding angle value.
      Formation mechanism of the composite coating based on fluorosilicone resin and
      modified nanoparticles was explained using interpenetrating polymer model.

PMID- 30109107
TI  - Analytical solution for bending vibration of a thin-walled cylinder rolling on a
      time-varying force.
AB  - This paper presents the analytical solution of radial vibration of a rolling
      cylinder submitted to a time-varying point force. In the simplest situation of
      simply supported edges and zero in-plane vibration, the cylinder is equivalent to
      an orthotropic pre-stressed plate resting on a visco-elastic foundation. We give
      the closed-form solution of vibration as a series of normal modes whose
      coefficients are explicitly calculated. Cases of both deterministic and random
      forces are examined. We analyse the effect of rolling speed on merging of
      vibrational energy induced by Doppler's effect for the example of rolling tyre.

PMID- 30109106
TI  - Design and implementation of levee project information management system based on
      WebGIS.
AB  - The China Levee Project Information Management System (CLPIMS) is an information
      management platform that was established for levee project management within the
      seven major river basins in China. The system was developed on the basis of the
      VS.NET and ArcGIS Server and was combined with the database theory and key
      techniques of WebGIS, which has the features of real-time display, enquiry,
      statistics and management of spatial data under browser/server mode. Moreover,
      additional applications, such as real-time monitoring, safety assessment, early
      warning and danger forecasting and online analysis, can be further explored
      through reserved modules. The CLPIMS can serve not only as a scientific,
      systematic, visual tool for analysis and decision management in levee projects in
      China but also as a technical platform for flood control practice. Furthermore,
      the system is capable of unified management and sharing of the levee project
      information for the seven major river basins in China, and it is important for
      the improvement of office automation, E-government applications and the level of
      flood control operations.

PMID- 30109108
TI  - On relativistic multipole moments of stationary space-times.
AB  - Among the known exact solutions of Einstein's vacuum field equations the Manko
      Novikov and the Quevedo-Mashhoon metrics might be suitable ones for the
      description of the exterior gravitational field of some real non-collapsed body.
      A new proposal to represent such exterior field is the stationary q-metric. In
      this contribution, we computed by means of the Fodor-Hoenselaers-Perjes formalism
      the lowest 10 relativistic multipole moments of these metrics. Corresponding
      moments were derived for the static vacuum solutions of Gutsunayev-Manko and
      Hernandez-Martin. A direct comparison between the multipole moments of these non
      isometric space-times is given.

PMID- 30109109
TI  - Novel acridine-based thiosemicarbazones as 'turn-on' chemosensors for selective
      recognition of fluoride anion: a spectroscopic and theoretical study.
AB  - New thiosemicarbazide-linked acridines 3a-c were prepared and investigated as
      chemosensors for the detection of biologically and environmentally important
      anions. The compounds 3a-c were found selective for fluoride (F-) with no
      affinity for other anions, i.e. -OAc, Br-, I-, HSO4-, SO42-, PO43-, ClO3-, ClO4-,
      CN- and SCN-. Further, upon the gradual addition of a fluoride anion (F-) source
      (tetrabutylammonium fluoride), a well-defined change in colour of the solution of
      probes 3a-c was observed. The anion-sensing process was studied in detail via UV
      visible absorption, fluorescence and 1H-NMR experiments. Moreover, during the
      synthesis of acridine probes 3a-c nickel fluoride (NiF2), a rarely explored
      transition metal fluoride salt, was used as the catalyst. Theoretical studies via
      density functional theory were also carried out to further investigate the
      sensing and anion (F-) selectivity pattern of these probes.

PMID- 30109110
TI  - Highly efficient triazolone/metal ion/polydopamine/MCM-41 sustained release
      system with pH sensitivity for pesticide delivery.
AB  - MCM-41 was prepared through the sol-gel method and encapsulated by polydopamine
      (PDA) before being coordinated with metal ions to form a highly efficient
      sustained release system (M-PDA-MCM-41) for triazolone delivery. The
      characterization results confirmed the existence of the coordination bond between
      the PDA layer and triazolone through the bridge effect from metal ions, which
      enhanced the interaction between PDA-MCM-41 and triazolone. The adsorption
      capacity of Fe-PDA-MCM-41 increased up to 173 mg g-1, which was 160% more than
      that of MCM-41. The sustained release performance of M-PDA-MCM-41 in different pH
      values was investigated. Under the conditions of pH <=7, the release speed of
      triazolone increased with pH decreasing, whereas its release speed in the weak
      base condition was slower than in the neutral condition. Therefore, the as
      synthesized system showed significant pH-sensitivity in the sustained release
      process, indicating that the sustained release system can be well stored in the
      neutral or basic environment and activated in the acid environment. Their
      sustained release curves described by the Korsmeyer-Peppas equation at pH 7
      showed the same behaviour, indicating that PDA decoration or metal ion
      coordination only increases the steric hindrance and the interaction between
      carrier and triazolone instead of changing the original structure of the pure MCM
      material in accordance with X-ray diffraction and Brunauer-Emmett-Teller analysis
      results.

PMID- 30109111
TI  - Zinc recovery from metallurgical slag and dust by coordination leaching in NH3
      CH3COONH4-H2O system.
AB  - Metallurgical slag and dust (MSD) from lead and zinc smelting, steel dust and
      galvanized steel scrap are important secondary sources of zinc and other valuable
      metals. This paper describes the production feasibility and rationality of a
      cleaner zinc recovery process using MSD and a hydrometallurgical method. It was
      found that the addition of CH3COONH4 to a NH3-H2O system promotes zinc
      extraction, and 83.76% of zinc could be dissolved and recovered from the MSD
      under the following conditions: total ammonia concentration of 5 mol l-1,
      stirring speed of 300 r.p.m., ammonia/ammonium ratio of 1 : 1, solid/liquid ratio
      of 1 : 5, leaching temperature of 25 degrees C and a leaching time of 60 min. A
      leaching kinetic study indicates that the leaching process is controlled by the
      diffusion and interface transfer and that the reaction apparent activation energy
      is 22.66 kJ mol-1. Fourier transform infrared spectroscopy and electrospray
      ionization mass spectrometry analysis showed that zinc can combine with the
      carboxylate anion to form Zn complexes such as [Zn2(Ac)3(NH3)2]+. Zn2SiO4, ZnS
      and ZnFe2O4 in NH3-CH3COONH4-H2O system did not disappear according to X-ray
      diffraction analysis for leaching residue.

PMID- 30109112
TI  - Plant-animal worms round themselves up in circular mills on the beach.
AB  - Collective motion is a fascinating and intensely studied manifestation of
      collective behaviour. Circular milling is an impressive example. It occurs in
      fishes, processionary caterpillars and army ants, among others. Its adaptive
      significance, however, is not yet well understood. Recently, we demonstrated
      experimentally circular milling in the marine plant-animal worm Symsagittifera
      roscoffensis. We hypothesized that its function is to gather the worms and
      facilitate the dense films they form on the beach to promote the photosynthesis
      of their symbiotic algae. Here, we report for the first time, to our knowledge,
      the occurrence of S. roscoffensis circular mills in nature and show that it is by
      no means rare. The size and behaviour of circular mills in their natural
      environment is compatible with our earlier experimental results. This makes S.
      roscoffensis a good study system for understanding the proximate and ultimate
      mechanisms of circular milling.

PMID- 30109113
TI  - Structural, elastic, mechanical and thermodynamic properties of HfB4 under high
      pressure.
AB  - The present work aims to study the structural, elastic, mechanical and
      thermodynamic properties of the newly discovered orthorhombic Cmcm structure HfB4
      (denoted as Cmcm-HfB4 hereafter) under pressure by the first-principles
      calculations. The obtained equilibrium structure parameters and ground-state
      mechanical properties were in excellent agreement with the other theoretical
      results. The calculated elastic constants and phonon dispersion spectra show that
      Cmcm-HfB4 is mechanically and dynamically stable up to 100 GPa and no phase
      transition was observed. An analysis of the elastic modulus indicates that Cmcm
      HfB4 possesses a large bulk modulus, shear modulus and Young's modulus. The
      superior mechanical properties identify this compound as a possible candidate for
      a superhard material. Further hardness calculation confirmed that this compound
      is a superhard material with high hardness (45.5 GPa for GGA); and the relatively
      strong B-B covalent bonds' interaction and the planar six-membered ring boron
      network in Cmcm-HfB4 are crucial for the high hardness. Additionally, the
      pressure-induced elastic anisotropy behaviour has been analysed by several
      different anisotropic indexes. By calculating the B/G and Poisson's ratio, it is
      predicted that Cmcm-HfB4 possesses brittle behaviour in the range of pressure
      from 0 to 100 GPa, and higher pressures can reduce its brittleness. Finally, the
      thermodynamic properties, including enthalpy (DeltaH), free energy (DeltaG),
      entropy (DeltaS), heat capacity (CV ) and Debye temperature (ThetaD ) are
      obtained under pressure and temperature, and the results are also interpreted.

PMID- 30109115
TI  - Storage stability of organophosphorus pesticide residues in peanut and soya bean
      extracted solutions.
AB  - This study was performed to determine the storage stability of organophosphorus
      pesticide residues in high oil content commodity matrices, peanut and soya bean.
      The storage conditions included different types of solvents (ethyl acetate,
      acetone and hexane) and corresponding extracted matrix solutions, light and
      temperature. It was found that three pesticides degraded quickly especially in
      ethyl acetate solvent. They decreased greater than 30% when stored for 3 days at 
      20 degrees C in ethyl acetate; the results showed that the stability could be
      improved in the extracted matrix solutions. Light had a slight effect for
      stability of phorate and fenthion, while it played an important effect for
      disulfoton with the exception of ethyl acetate as solvent. Even at -20 degrees C,
      exposure to solvents or extracted matrix solution resulted in 40.67, 96.33 and
      35.07% loss of phorate, disulfoton and fenthion. Hence, it could be assumed that
      these three residues could be more stable at lower temperature, in the dark and
      in acetone or hexane extracted peanut and soya bean solutions.

PMID- 30109116
TI  - Correction to 'Synergestic effect of acidity and extraframework position in
      faujasite on renewable p-xylene production'.
AB  - [This corrects the article DOI: 10.1098/rsos.172471.].

PMID- 30109114
TI  - Decomposing the effects of ocean environments on predator-prey body-size
      relationships in food webs.
AB  - Body-size relationships between predators and their prey are important in
      ecological studies because they reflect the structure and function of food webs.
      Inspired by studies on the impact of global warming on food webs, the effects of
      temperature on body-size relationships have been widely investigated; however,
      the impact of environmental factors on body-size relationships has not been fully
      evaluated because climate warming affects various ocean environments. Thus, here,
      we comprehensively investigated the effects of ocean environments and predator
      prey body-size relationships by integrating a large-scale dataset of predator
      prey body-size relationships in marine food webs with global oceanographic data.
      We showed that various oceanographic parameters influence prey size selection. In
      particular, oxygen concentration, primary production and salinity, in addition to
      temperature, significantly alter body-size relationships. Furthermore, we
      demonstrated that variability (seasonality) of ocean environments significantly
      affects body-size relationships. The effects of ocean environments on body-size
      relationships were generally remarkable for small body sizes, but were also
      significant for large body sizes and were relatively weak for intermediate body
      sizes, in the cases of temperature seasonality, oxygen concentration and salinity
      variability. These findings break down the complex effects of ocean environments
      on body-size relationships, advancing our understanding of how ocean environments
      influence the structure and functioning of food webs.

PMID- 30109117
TI  - Acquired urea cycle amino acid deficiency and hyperammonaemic encephalopathy in a
      cat with inflammatory bowel disease and chronic kidney disease.
AB  - Case summary: A 5-year-old male neutered Persian cat was referred for
      investigation of a 4 week history of weight loss, inappetence and intermittent
      vomiting. Chronic kidney disease (CKD) and inflammatory bowel disease were
      diagnosed, and despite immunosuppressive therapy and assisted enteral nutrition,
      the cat experienced persistent anorexia, vomiting and severe weight loss. After 2
      additional weeks of treatment, the cat developed acute-onset neurological signs
      associated with severe hyperammonaemia and was euthanased. Plasma amino acid
      assessment revealed deficiency of several amino acids involved in the urea cycle,
      including arginine. Relevance and novel information: To our knowledge, this is
      the first reported case of an acquired urea cycle amino acid deficiency without
      nutritional deprivation in a cat. Several contributing factors were suspected,
      including intestinal malabsorption and CKD. This case demonstrates the importance
      of urea cycle amino acids in feline metabolism and possible necessity for
      parenteral supplementation, particularly in the context of persistent weight loss
      despite adequate enteral nutrition.

PMID- 30109118
TI  - Erratum: Author Correction: Redox-active conducting polymers modulate Salmonella
      biofilm formation by controlling availability of electron acceptors.
AB  - [This corrects the article DOI: 10.1038/s41522-017-0027-0.].

PMID- 30109119
TI  - Impact of active and passive social facilitation on self-paced endurance and
      sprint exercise: encouragement augments performance and motivation to exercise.
AB  - Objective: The positive effect of an audience on performance is anecdotally well
      known, but the impact of such social facilitation to both performance and the
      motivation to exercise have not been thoroughly explored. The aim of this study
      was therefore to investigate verbal encouragement as a means to promote positive
      behavioural adherence to exercise and augmented performance. Methods: Twelve
      untrained but active individuals (seven female), age 24+/-3 years participated in
      this study. Exercise conditions with external verbal encouragement (EVE) and
      without external verbal encouragement (WEVE) were compared in both endurance (20
      min) and sprint (2 * 30 s Wingate) cycling tasks in a randomised crossover
      design. Results were analysed by separate 2 (EVE/WEVE) * 2 (sprint/endurance)
      within-subjects analyses of variance for each dependent variable. Statistical
      significance was set at p<=0.05. Results: EVE resulted in a significant increase,
      F(1,11)=15.37, p=0.002, etap2=0.58 in the average power generated by participants
      in each exercise bout on the cycle ergometer. EVE also had a significant effect
      on reported motivation to exercise the next day, F(1,11)=5.5, p=0.04, etap2
      =0.33, which did not differ between type of exercise. Conclusion: External
      encouragement in both sprint and endurance activities resulted in large
      improvements in performance and motivation to continue an exercise regimen the
      next day, which has important implications for health, adherence and maximising
      physical performance using a practical intervention.

PMID- 30109120
TI  - DNA methylation reprogramming of functional elements during mammalian embryonic
      development.
AB  - DNA methylation plays important roles during development. However, the DNA
      methylation reprogramming of functional elements has not been fully investigated
      during mammalian embryonic development. Herein, using our modified MethylC-Seq
      library generation method and published post-bisulphite adapter-tagging (PBAT)
      method, we generated genome-wide DNA methylomes of human gametes and early
      embryos at single-base resolution and compared them with mouse methylomes. We
      showed that the dynamics of DNA methylation in functional elements are conserved
      between humans and mice during early embryogenesis, except for satellite repeats.
      We further found that oocyte-specific hypomethylated promoters usually exhibit
      low CpG densities. Genes with oocyte-specific hypomethylated promoters generally
      show oocyte-specific hypomethylated genic and intergenic regions, and these
      hypomethylated regions contribute to the hypomethylation pattern of mammalian
      oocytes. Furthermore, hypomethylated genic regions with low CG densities
      correlate with gene silencing in oocytes, whereas hypomethylated genic regions
      with high CG densities correspond to high gene expression. We further show that
      methylation reprogramming of enhancers during early embryogenesis is highly
      associated with the development of almost all human organs. Our data support the
      hypothesis that DNA methylation plays important roles during mammalian
      development.

PMID- 30109122
TI  - Supramolecular assembly of KAT2A with succinyl-CoA for histone succinylation.

PMID- 30109123
TI  - Exome sequencing for paediatric-onset diseases: impact of the extensive
      involvement of medical geneticists in the diagnostic odyssey.
AB  - Currently, offering whole-exome sequencing (WES) via collaboration with an
      external laboratory is increasingly common. However, the receipt of a WES report
      can be merely the beginning of a continuing exploration process rather than the
      end of the diagnostic odyssey. The laboratory often does not have the information
      the physician has, and any discrepancies in variant interpretation must be
      addressed by a medical geneticist. In this study, we performed diagnostic WES of
      104 patients with paediatric-onset genetic diseases. The post-exome review of WES
      reports by the clinical geneticist led to a more comprehensive assessment of
      variant pathogenicity in 16 cases. The overall diagnostic yield was 41% (n = 43).
      Among these 43 diagnoses, 51% (22/43) of the pathogenic variants were nucleotide
      changes that have not been previously reported. The time required for the post
      exome review of the WES reports varied, and 26% (n = 27) of the reports required
      an extensive amount of time (>3 h) for the geneticist to review. In this
      predominantly Chinese cohort, we highlight the importance of discrepancies
      between global and ethnic-specific frequencies of a genetic variant that
      complicate variant interpretation and the significance of post-exome diagnostic
      modalities in genetic diagnosis using WES. The challenges faced by geneticists in
      interpreting WES reports are also discussed.

PMID- 30109121
TI  - Merge and separation of NuA4 and SWR1 complexes control cell fate plasticity in
      Candida albicans.
AB  - Phenotypic plasticity is common in development. Candida albicans, a polymorphic
      fungal pathogen of humans, possesses the unique ability to achieve rapid and
      reversible cell fate between unicellular form (yeast) and multicellular form
      (hypha) in response to environmental cues. The NuA4 histone acetyltransferase
      activity and Hda1 histone deacetylase activity have been reported to be required
      for hyphal initiation and maintenance. However, how Hda1 and NuA4 regulate hyphal
      elongation is not clear. NuA4 histone acetyltransferase and SWR1 chromatin
      remodeling complexes are conserved from yeast to human, which may have merged
      together to form a larger TIP60 complex since the origin of metazoan. In this
      study, we show a dynamic merge and separation of NuA4 and SWR1 complexes in C.
      albicans. NuA4 and SWR1 merge together in yeast state and separate into two
      distinct complexes in hyphal state. We demonstrate that acetylation of Eaf1 K173
      controls the interaction between the two complexes. The YEATS domain of Yaf9 in
      C. albicans can recognize an acetyl-lysine of the Eaf1 and mediate the Yaf9-Eaf1
      interaction. The reversible acetylation and deacetylation of Eaf1 by Esa1 and
      Hda1 control the merge and separation of NuA4 and SWR1, and this regulation is
      triggered by Brg1 recruitment of Hda1 to chromatin in response nutritional
      signals that sustain hyphal elongation. We have also observed an orchestrated
      promoter association of Esa1, Hda1, Swr1, and H2A.Z during the reversible yeast
      hyphae transitions. This is the first discovery of a regulated merge of the NuA4
      and SWR1 complexes that controls cell fate determination and this regulation may
      be conserved in polymorphic fungi.

PMID- 30109124
TI  - Whole-genome analysis for effective clinical diagnosis and gene discovery in
      early infantile epileptic encephalopathy.
AB  - Early infantile epileptic encephalopathy (EIEE) is a devastating epilepsy
      syndrome with onset in the first months of life. Although mutations in more than
      50 different genes are known to cause EIEE, current diagnostic yields with gene
      panel tests or whole-exome sequencing are below 60%. We applied whole-genome
      analysis (WGA) consisting of whole-genome sequencing and comprehensive variant
      discovery approaches to a cohort of 14 EIEE subjects for whom prior genetic tests
      had not yielded a diagnosis. We identified both de novo point and INDEL mutations
      and de novo structural rearrangements in known EIEE genes, as well as mutations
      in genes not previously associated with EIEE. The detection of a pathogenic or
      likely pathogenic mutation in all 14 subjects demonstrates the utility of WGA to
      reduce the time and costs of clinical diagnosis of EIEE. While exome sequencing
      may have detected 12 of the 14 causal mutations, 3 of the 12 patients received
      non-diagnostic exome panel tests prior to genome sequencing. Thus, given the
      continued decline of sequencing costs, our results support the use of WGA with
      comprehensive variant discovery as an efficient strategy for the clinical
      diagnosis of EIEE and other genetic conditions.

PMID- 30109125
TI  - Early effects of previous experience on conscious perception.
AB  - Constructive theories of brain function such as predictive coding posit that
      prior knowledge affects our experience of the world quickly and directly.
      However, it is yet unknown how swiftly prior knowledge impacts the neural
      processes giving rise to conscious experience. Here we used an experimental
      paradigm where prior knowledge augmented perception and measured the timing of
      this effect with magnetoencephalography (MEG). By correlating the perceptual
      benefits of prior knowledge with the MEG activity, we found that prior knowledge
      took effect in the time-window 80-95 ms after stimulus onset, thus reflecting an
      early influence on conscious perception. The sources of this effect were
      localized to occipital and posterior parietal regions. These results are in line
      with the predictive coding framework.

PMID- 30109128
TI  - Is conscious awareness needed for all working memory processes?
AB  - Stein and colleagues argue there is no yet conclusive evidence for nonconscious
      working memory (WM) and that is critical to probe WM while ensuring null
      sensitivity to memory cues. While this stringent approach reduces the likelihood
      of nonconscious signaling for WM, we discuss existing work meeting this null
      sensitivity criteria, and, related work on nonconscious cognition in keeping with
      WM/awareness dissociations on the basis of a functional operational definition of
      WM. Further, because it is likely that WM is a nonunitary functional construct
      and visual awareness a gradual phenomenon, we propose that delineating the neural
      mechanisms for distinct WM types across different levels of awareness may prove
      the most fruitful approach for understanding the interplay between WM and
      consciousness.

PMID- 30109126
TI  - Dual-process theories and consciousness: the case for 'Type Zero' cognition.
AB  - A step towards a theory of consciousness would be to characterize the effect of
      consciousness on information processing. One set of results suggests that the
      effect of consciousness is to interfere with computations that are optimally
      performed non-consciously. Another set of results suggests that conscious, system
      2 processing is the home of norm-compliant computation. This is contrasted with
      system 1 processing, thought to be typically unconscious, which operates with
      useful but error-prone heuristics. These results can be reconciled by separating
      out two different distinctions: between conscious and non-conscious
      representations, on the one hand, and between automatic and deliberate processes,
      on the other. This pair of distinctions is used to illuminate some existing
      experimental results and to resolve the puzzle about whether consciousness helps
      or hinders accurate information processing. This way of resolving the puzzle
      shows the importance of another category, which we label 'type 0 cognition',
      characterized by automatic computational processes operating on non-conscious
      representations.

PMID- 30109127
TI  - Visual gravity contributes to subjective first-person perspective.
AB  - A fundamental component of conscious experience involves a first-person
      perspective (1PP), characterized by the experience of being a subject and of
      being directed at the world. Extending earlier work on multisensory perceptual
      mechanisms of 1PP, we here asked whether the experienced direction of the 1PP
      (i.e. the spatial direction of subjective experience of the world) depends on
      visual-tactile-vestibular conflicts, including the direction of gravity. Sixteen
      healthy subjects in supine position received visuo-tactile synchronous or
      asynchronous stroking to induce a full-body illusion. In the critical
      manipulation, we presented gravitational visual object motion directed toward or
      away from the participant's body and thus congruent or incongruent with respect
      to the direction of vestibular and somatosensory gravitational cues. The results
      showed that multisensory gravitational conflict induced within-subject changes of
      the experienced direction of the 1PP that depended on the direction of visual
      gravitational cues. Participants experienced more often a downward direction of
      their 1PP (incongruent with respect to the participant's physical body posture)
      when visual object motion was directed away rather than towards the participant's
      body. These downward-directed 1PP experiences positively correlated with measures
      of elevated self-location. Together, these results show that visual gravitational
      cues contribute to the experienced direction of the 1PP, defining the subjective
      location and perspective from where humans experience to perceive the world.

PMID- 30109130
TI  - The temporal advantage for reloading vs. uploading conscious representations
      decays over time.
AB  - In motion-induced blindness (MIB), a static target superimposed on a global
      moving pattern frequently disappears and reappears into consciousness. We
      previously reported an intriguing illusory temporal reversal whereby a new
      stimulus onset (e.g. a dot flash) presented during MIB triggers an early
      reappearance of the target, yet is systematically perceived as occurring after
      the target reappearance. This illusion implies that the unconscious target
      representation can be quickly reactivated, with a temporal advantage for its
      conscious reloading as compared to the conscious uploading of a newly presented
      visual stimulus. However, it remains unclear whether the temporal advantage for
      conscious representation reloading strengthens, decays, or remains constant over
      time after we lose the initial conscious access to the stimulus. To address this
      question, we examined the relation between the duration of MIB and the percentage
      of illusory temporal reversals, and we found a negative correlation between the
      two measures, both between and within observers. The results suggest that
      although the unconscious target representation retains a certain level of
      activation during MIB, the temporal advantage for reloading its preexisting
      representation into consciousness decays over time.

PMID- 30109129
TI  - Unconscious semantic processing of polysemous words is not automatic.
AB  - Semantic processing of visually presented words can be identified both on
      behavioral and neurophysiological evidence. One of the major discoveries of the
      last decades is the demonstration that these signatures of semantic processing,
      initially observed for consciously perceived words, can also be detected for
      masked words inaccessible to conscious reports. In this context, the distinction
      between conscious and unconscious verbal semantic processing constitutes a
      challenging scientific issue. A prominent view considered that while conscious
      representations are subject to executive control, unconscious ones would operate
      automatically in a modular way, independent from control and top-down influences.
      Recent findings challenged this view by revealing that endogenous attention and
      task-setting can have a strong influence on unconscious processing. However, one
      of the major arguments supporting the automaticity of unconscious semantic
      processing still stands, stemming from a seminal observation reported by Marcel
      in 1980 about polysemous words. In the present study we reexamined this evidence.
      We present a combination of behavioral and event-related-potentials (ERPs)
      results that refute this view by showing that the current conscious semantic
      context has a major and similar influence on the semantic processing of both
      visible and masked polysemous words. In a classical lexical decision task, a
      polysemous word was preceded by a word which defined the current semantic
      context. Crucially, this context was associated with only one of the two meanings
      of the polysemous word, and was followed by a word/pseudo-word target. Behavioral
      and electrophysiological evidence of semantic priming of target words by masked
      polysemous words was strongly dependent on the conscious context. Moreover, we
      describe a new type of influence related to the response-code used to answer for
      target words in the lexical decision task: unconscious semantic priming
      constrained by the conscious context was present both in behavior and ERPs
      exclusively when right-handed subjects were instructed to respond to words with
      their right hand. The strong and respective influences of conscious context and
      response-code on semantic processing of masked polysemous words demonstrate that
      unconscious verbal semantic representations are not automatic.

PMID- 30109131
TI  - Task relevance differentially shapes ventral visual stream sensitivity to visible
      and invisible faces.
AB  - Top-down modulations of the visual cortex can be driven by task relevance. Yet,
      several accounts propose that the perceptual inferences underlying conscious
      recognition involve similar top-down modulations of sensory responses. Studying
      the pure impact of task relevance on sensory responses requires dissociating it
      from the top-down influences underlying conscious recognition. Here, using visual
      masking to abolish perceptual consciousness in humans, we report that functional
      magnetic resonance imaging (fMRI) responses to invisible faces in the fusiform
      gyrus are enhanced when they are task-relevant, but suppressed when they are task
      irrelevant compared to other object categories. Under conscious perceptual
      conditions, task-related modulations were also present but drastically reduced,
      with visible faces always eliciting greater activity in the fusiform gyrus
      compared to other object categories. Thus, task relevance crucially shapes the
      sensitivity of fusiform regions to face stimuli, leading from enhancement to
      suppression of neural activity when the top-down influences accruing from
      conscious recognition are prevented.

PMID- 30109134
TI  - The enigma of cannabis use in spinal cord injury.
AB  - Cannabis use in medicine continues to confound practitioners. There is confusing
      interpretation of the efficacy and adverse event data, highlighting the
      complexity of this unique plant. Cannabis may have a neuroprotective role in SCI.

PMID- 30109133
TI  - Cannabis shenanigans: advocating for the restoration of an effective treatment of
      pain following spinal cord injury.
AB  - Cannabis is an effective treatment for pain following spinal cord injury that
      should be available to patients and researchers. The major argument against the
      rescheduling of cannabis is that the published research is not convincing. This
      argument is disingenuous at best, given that the evidence has been presented and
      rejected at many points during the political dialog. Moreover, the original
      decision to criminalize cannabis did not utilize scientific or medical data.
      There is tension between the needs of a society to protect the vulnerable by
      restricting the rights of others to live well and with less pain. It is clear
      that this 70-year war on cannabis has had little effect in controlling the supply
      of cannabis. Prohibition can never succeed; "it is a tyranny from which every
      independent mind revolts." People living with chronic pain should not have to
      risk addiction, social stigma, restrictions on employment and even criminal
      prosecution in order to deal with their pain. It is time to end the shenanigans
      and have an open, transparent discussion of the true benefits of this much
      beleaguered medicine.

PMID- 30109132
TI  - Pre-reproductive stress and fluoxetine treatment in rats affect offspring A-to-I
      RNA editing, gene expression and social behavior.
AB  - Adenosine to inosine RNA editing is an epigenetic process that entails site
      specific modifications in double-stranded RNA molecules, catalyzed by adenosine
      deaminases acting on RNA (ADARs). Using the multiplex microfluidic PCR and deep
      sequencing technique, we recently showed that exposing adolescent female rats to
      chronic unpredictable stress before reproduction affects editing in the
      prefrontal cortex and amygdala of their newborn offspring, particularly at the
      serotonin receptor 5-HT2c (encoded by Htr2c). Here, we used the same technique to
      determine whether post-stress, pre-reproductive maternal treatment with
      fluoxetine (5 mg/kg, 7 days) reverses the effects of stress on editing. We also
      examined the mRNA expression of ADAR enzymes in these regions, and asked whether
      social behavior in adult offspring would be altered by maternal exposure to
      stress and/or fluoxetine. Maternal treatment with fluoxetine altered Htr2c
      editing in offspring amygdala at birth, enhanced the expression of Htr2c mRNA and
      RNA editing enzymes in the prefrontal cortex, and reversed the effects of pre
      reproductive stress on Htr2c editing in this region. Furthermore, maternal
      fluoxetine treatment enhanced differences in editing of glutamate receptors
      between offspring of control and stress-exposed rats, and led to enhanced social
      preference in adult offspring. Our findings indicate that pre-gestational
      fluoxetine treatment affects patterns of RNA editing and editing enzyme
      expression in neonatal offspring brain in a region-specific manner, in
      interaction with pre-reproductive stress. Overall, these findings imply that
      fluoxetine treatment affects serotonergic signaling in offspring brain even when
      treatment is discontinued before gestation, and its effects may depend upon prior
      exposure to stress.

PMID- 30109135
TI  - Electronic medical record: data collection and reporting for spinal cord injury.
AB  - Study design: Presentation of implementation of International Spinal Cord Injury
      (SCI) Data Sets, International Standards for Neurological Classification of SCI
      (ISNCSCI), and other structured SCI tools in to the Electronic Medical Record
      (EMR) Epic. Objectives: To describe the implementation of SCI tools in Epic at
      Rigshospitalet, University of Hospital, Capital Region of Denmark, and the
      ambitions for the future development of SCI related structured data and their
      reporting in the Epic EMR to be able to standardize data collection to facilitate
      research within institutions and collaboratively with other institutions locally
      and globally. Setting: Denmark and United States of America. Methods: The general
      content of the EMR Epic and the SCI-specific structured data implemented are
      described as well as the tools for reporting. Results: The ISNCSCI is made
      available via access to http://isncscialgorithm.azurewebsites.net/. After filling
      in the test data on the website, one can save the completed form as an image
      within the patient's chart. The International SCI Core Data Set and 13
      International SCI Basic Data Sets (Table 1) are nearly completely implemented in
      the Danish version of Epic as SmartForms. In addition, 14 functional measures,
      including the Spinal Cord Independence Measure III, are implemented as flowsheets
      (Table 2). Conclusions: The possibility of entering international recognized
      structured data into the EMR gives better possibility for data sharing across SCI
      centers worldwide. Sponsorship: Gianna Maria Rodriguez, Stacey Cohen, and Fin
      Biering-Sorensen are users of Epic, but have no economic relationship with Epic.
      Kelly Tausk and Josh Martin are employees of Epic.

PMID- 30109136
TI  - Predicting quality of life among family caregivers of people with spinal cord
      injury having chronic low back pain in Nepal: a cross-sectional pilot study.
AB  - Study design: Descriptive cross-sectional study. Objective: This study aims to
      determine the factors predicting quality of life among Nepalese family caregivers
      of people with spinal cord injury (SCI) having low back pain. Setting: Eight
      districts of the Bagmati Zone of Nepal. Methods: Sixty-five family caregivers of
      people with SCI having chronic low back pain were recruited from January to March
      2017. The factors examined as independent variables included monthly household
      income, daily caregiving hours, functional independence of people with SCI, low
      back pain intensity, and functional disability of family caregivers. The measures
      were the Family Caregivers' and Spinal Cord Injury Patients' Demographic Form,
      the Modified Barthel Index, the Pain Intensity Scale, the Oswestry Disability
      Index, and the World Health Organization Quality of Life-BREF Nepali version. A
      hierarchical multiple regression analysis was used to predict quality of life.
      Results: Functional independence of people with SCI, monthly household income,
      and functional disability of family caregivers with chronic low back pain could
      significantly predict quality of life at 41% (adjusted R2 = 0.41, Fchange (3,59)
      = 11.02, p < 0.01). The functional dependence of persons with SCI was the most
      powerful factor contributing to QoL of caregivers (beta = 0.36, p < 0.01)
      followed by monthly household income (beta = 0.30, p < 0.01) and caregivers'
      functional disability (beta = -0.28, p < 0.01). Conclusion: The findings
      suggested that in order to improve the quality of life of family caregivers who
      have chronic low back pain while providing care for people with SCI during a long
      period, health professionals should strengthen the functional independence of the
      patients after discharge to reduce the functional disability of the caregivers.
      Financial support is needed for caregivers who have a low income.

PMID- 30109137
TI  - Infected charcot spine arthropathy.
AB  - Background: Charcot spinal arthropathy (CSA), a destructive spinal pathology, is
      seen in patients with impaired sensation. Superimposed infection in the affected
      spinal segments can lead to a challenge in the diagnosis and management. Spinal
      cord injury (SCI) is the leading cause of CSA as persons with SCI have
      significantly impaired sensation. Though infection of the CSA is rare, SCI
      persons are prone to superimposed infection of the Charcot spine. We report
      atypical presentations of three cases of CSA with superimposed infection. Case
      descriptions: A 47-year-old male with complete T7-8 SCI developed symptoms
      suggestive of infection and CSA. He was managed with a posterior vertebral column
      resection (PVCR) of T12 and intravenous antibiotics as the intraoperative culture
      showed the growth of E. coli and Pseudomonas. A 26-year-old male with T12
      complete paraplegia, post status post open reduction and internal fixation with
      subsequent implants removal developed infection and CSA over the pseudo-arthrotic
      lesion with destruction of T12 and L1 vertebrae and an external fistulous track.
      He was managed with debridement and anterior column T11-L1 reconstruction with a
      Titanium cage and four-rod pedicle screw stabilization construct. A 25-year-old
      male with complete paraplegia with CSA at L4-S1. He underwent PVCR of L5 and L3
      S2 posterior stabilization. The intraoperative culture and histopathology were
      suggestive of tuberculous infection. Conclusion: Pyogenic or tubercular infection
      of CSA should be considered as a diagnostic possibility in persons with SCI who
      are more prone to infections. The management includes aggressive debridement and
      circumferential fusion along with appropriate medications to control the
      infection.

PMID- 30109138
TI  - Epidemiology of spinal fractures and associated spinal cord injuries in Iceland.
AB  - Study design: A retrospective epidemiological study. Setting: Landspitali
      University Hospital, Iceland. Objectives: Assessment of epidemiological data and
      risk factors for traumatic spinal fractures (SFs) and associated spinal cord
      injury (SCI). Methods: A retrospective review of hospital admissions due to
      traumatic SFs during a 5-year period, with analysis of epidemiological parameters
      and occurrence of concomitant SCI. Patients with asymptomatic SFs and non
      traumatic SCI were excluded. Results: A total of 487 patients were diagnosed with
      a SF or 310 PMI (per million inhabitants), 42 of them (9%, 27 PMI) with an
      associated SCI. The mean age was 56 years, males were 57%. Falls were the leading
      cause of both SFs (49%) and SCIs (43%). Low falls (<1 m) caused SFs more often in
      elderly women (67%, mean age 77 years) and more than 96% were without SCI. Road
      traffic accidents (RTA) caused 31% of SFs and 26% of SCIs. Seat belts were not
      used in 20% of car accidents, but information was missing in 27%. Sports/leisure
      related accidents caused SFs in 12% of cases, whereof horseback riding accidents
      were the most common (36%). Conclusions: SFs led to SCI in 9% of patients.
      Several risk factors were common for SFs and SCIs but two major differences were
      seen: SFs without SCI were most common in older women due to low falls, while the
      risk of a concomitant SCI increased in young patients, in males, in falls from
      high levels and when driving without using seat belts. Preventive efforts should
      therefore be directed towards these risk factors.

PMID- 30109139
TI  - Symptomatic spinal epidural lipomatosis after combined hormonal and steroidal
      palliative therapy of prostate cancer.
AB  - Introduction: Spinal epidural lipomatosis (SLE) is an abnormal accumulation of
      unencapsulated fat. The association of chronic steroid therapy is described as
      well as obesity and Cushing's syndrome. SLE has a range of neurological
      presentations such as back pain, myelopathy, and cauda equina syndrome. Surgical
      decompression is known to improve symptomatic cases and prevent further
      deterioration. Case presentation: An elderly male patient with background history
      of high-risk metastatic prostate cancer and long-term treatment with steroids and
      hormonal therapy presented with acute on chronic back pain and neurological
      symptoms. Spinal cord compression was excluded on the subsequent MRI. However, a
      spinal epidural lipomatosis causing significant central canal stenosis and
      compression of the cauda equine was revealed. Discussion: With the increasing
      role of MRI in assessing back pain, asymptomatic spinal epidural lipomatosis has
      been frequently noticed. However, symptomatic presentation after long term
      combined treatment of steroids and hormonal therapy has not been reported in the
      literature.

PMID- 30109140
TI  - Downregulated circulating microRNAs after surgery: potential noninvasive
      biomarkers for diagnosis and prognosis of early breast cancer.
AB  - Success in curing breast cancer largely depends on the stage at diagnosis.
      Circulating microRNAs are becoming a promising noninvasive biomarker. We
      postulate that a postoperative decline in circulating microRNAs might have
      diagnostic and prognostic value. Applying high-throughput microarrays, we
      screened the dysregulated microRNAs in paired serum samples before and after
      surgery. The relative concentrations of putative markers between the early breast
      cancer and cancer-free groups were evaluated in the training set and verified in
      the validation set. Sensitivity, specificity, and receiver operating
      characteristic (ROC) curves were used to assess diagnostic value. Survival
      analysis was performed using Kaplan-Meier estimates and a Cox proportional
      hazards model. Five microRNAs significantly reduced after surgery were selected
      for the training set. We found that miR-130b-5p, miR-151a-5p, miR-206, and miR
      222-3p were significantly higher in the breast cancer group. Each of the four
      microRNAs had potential diagnostic value. The combined four microRNAs (training
      set: area under the curve (AUC) 0.8457; validation set: AUC 0.9309) had better
      diagnostic value than each single microRNA. MiR-222-3p was an independent
      prognostic factor for disease-free survival (HR = 13.19; 95% CI, 1.06-163.59; P =
      0.045). Patients with no fewer than three highly expressed miRNAs had shorter DFS
      than patients with 0-2 highly expressed miRNAs (HR = 2.293; 95% CI, 1.128-0.662;
      P = 0.022). Our findings indicate that postoperatively downregulated circulating
      miR-130b-5p, miR-151a-5p, miR-206, and miR-222-3p may be potential biomarkers for
      breast cancer diagnosis and prognosis.

PMID- 30109141
TI  - Notch3/VEGF-A axis is involved in TAT-mediated proliferation of pulmonary artery
      smooth muscle cells: Implications for HIV-associated PAH.
AB  - The incidence of pulmonary arterial hypertension (PAH) is a significant co
      morbidity observed in HIV (+) individuals. Pulmonary artery smooth muscle cells
      (PASMCs)-key components of the arterial vessel wall that regulate vessel
      diameter, demonstrate increased proliferation and hypertrophy in the lungs of HIV
      infected individuals, underscoring the role of these cells in the pathogenesis of
      HIV-associated PAH. While several pathways have been implicated in enhanced
      proliferation of PASMCs, detailed molecular mechanism(s) underlying HIV
      associated PASMC proliferation still remain elusive. In the current study, we
      sought to investigate the effects HIV protein transactivator of transcription
      (TAT)-mediated proliferation on PASMCs. In agreement with earlier findings, our
      results also demonstrated TAT-mediated proliferation of human PASMCs. We
      identified activation of a novel Notch3 signaling pathway in TAT-mediated
      proliferation of PASMCs. Further validation of the Notch 3 pathway was
      demonstrated using both pharmacological (gamma-secretase inhibitor, DAPT), as
      well as genetic approaches (Notch3 siRNA). Vascular endothelial growth factor A
      (VEGF-A) was identified as a novel downstream molecule that was induced following
      Notch activation. Findings from in vitro studies were further validated in
      archived simian immunodeficiency virus (SIV)-infected monkey lung tissues. There
      was increased activation of Notch3 signaling as well as enhanced expression of
      VEGF-A in the lungs of SIV-infected macaques compared with the lungs of SIV(-)
      controls. Taken together, we demonstrated that HIV-TAT increased the
      proliferation of PASMCs via the Notch3/VEGF-A axis. Targeting the Notch3/VEGF-A
      axis could thus be considered a potential therapeutic approach for the treatment
      of HIV-associated PAH.

PMID- 30109142
TI  - Increased Kruppel-like factor 12 impairs embryo attachment via downregulation of
      leukemia inhibitory factor in women with recurrent implantation failure.
AB  - Recurrent implantation failure (RIF) caused by various etiological factors
      remains a challenge for fertility clinicians using assisted reproductive
      technology (ART) worldwide. Dysregulation of leukemia inhibitory factor (LIF) in
      the endometria of women with RIF is involved in impaired endometrial receptivity
      and embryo adhesion. However, the mechanism through which LIF expression is
      regulated in women with RIF is still poorly understood. Our previous study noted
      that the abnormally increased endometrial Kruppel-like factor 12 (KLF12) in RIF
      women led to impaired decidualization and embryo implantation. Here, we further
      found that KLF12 inhibited embryo adhesion in vivo and in vitro by repressing LIF
      expression. Mechanistically, KLF12 bound to conserved sites (CAGTGGG, -6771 to 
      6765 and -7115 to -7109) within the LIF promoter region and repressed LIF
      transcription directly. Exogenous LIF significantly reversed the KLF12-mediated
      repression of BeWo spheroid adhesion. KLF12 expression was reduced significantly
      in Ishikawa cells treated with progestogen, which was due to the activation of
      Akt signaling. These findings may provide novel potential therapeutic regimens
      for patients with RIF and disrupted endometrial receptivity.

PMID- 30109143
TI  - Increased glutamine anabolism sensitizes non-small cell lung cancer to gefitinib
      treatment.
AB  - To better understand the resistance mechanism of non-small cell lung cancers
      (NSCLCs) to gefitinib, the metabolic profiles of gefitinib-resistant A549 cells
      and gefitinib-sensitive PC-9 cells were analyzed with a metabolomics analytical
      platform. A549 and PC-9 cells exhibited significant differences in the levels of
      glutamine-related metabolites. After gefitinib treatment, the glutamine level
      decreased in A549 cells but showed no change in PC-9 cells. The glutamine
      consumed by A549 cells was used to generate ATP and glutathione (GSH). As
      glutamine utilization was suppressed in gefitinib-treated PC-9 cells, the
      resulting ATP shortage and ROS accumulation led to cell death. The difference in
      glutamine metabolism was caused by differential changes in the levels of
      glutamine synthetase (GS, encoded by glutamate-ammonia ligase (GLUL)). GLUL
      expression was upregulated in gefitinib-sensitive cells, but it was either absent
      from gefitinib-resistant cells or no significant change was observed in the
      gefitinib-treated cells. GLUL overexpression in A549 cells significant sensitized
      them to gefitinib and decreased their invasive capacity. Conversely, knockout GS
      in PC-9 cells reduced gefitinib sensitivity and enhanced metastasis. Furthermore,
      the continuous exposure of gefitinib-sensitive HCC827 cells to gefitinib created
      gefitinib-resistant (GR) HCC827 cells, which exhibited a GLUL deletion and
      resistance to gefitinib. Thus, GLUL plays a vital role in determining the
      sensitivity of NSCLCs to gefitinib. Elevated GS levels mediate increased
      glutamine anabolism, and this novel mechanism sensitizes NSCLCs to gefitinib. The
      inhibition of glutamine utilization may serve as a potential therapeutic strategy
      to overcome gefitinib resistance in the clinic.

PMID- 30109144
TI  - Two novel SHP-1 agonists, SC-43 and SC-78, are more potent than regorafenib in
      suppressing the in vitro stemness of human colorectal cancer cells.
AB  - Signal transducer and activator of transcription 3 (STAT3) has been shown to play
      a critical role in the maintenance of cancer stem cells (CSCs). Hence, the
      inhibition of STAT3 signaling has been suggested to be a viable therapeutic
      approach for cancers. Moreover, the efficacy of combinations of chemotherapeutic
      drugs and napabucasin, a small-molecule STAT3 inhibitor, have been assessed in
      various clinical trials, including those involving patients with metastatic
      colorectal cancer (CRC). Two recently developed small-molecule STAT3 inhibitors,
      SC-43 and SC-78, which can stimulate SHP-1 to inactivate STAT3, were found to
      have anti-tumor activity. In this study, the inhibitory effects of SC-43, SC-78,
      and regorafenib (a reference drug) on cell viability, STAT3 phosphorylation, and
      various stemness properties [e.g., sphere-forming and soft agar colony-forming
      abilities, CD133+/CD44+ (stem cell-like) subpopulations, and the expression of
      several CSC markers] were examined for both HCT-116 and HT-29 human CRC cells. We
      found that SC-43 and SC-78 but not regorafenib inhibited constitutive and IL-6
      induced STAT3 phosphorylation in HCT-116 and HT-29 cells, respectively. Moreover,
      SC-43 and SC-78 were more potent than regorafenib in suppressing the stemness
      properties (except stem cell-like subpopulations) of these cells. As expected,
      SHP-1 knockdown almost completely abolished the suppressive effects of SC-43 and
      SC-78 on the sphere formation in both cell lines. Furthermore, SC-43 and SC-78
      showed synergistic inhibitory effects with oxaliplatin and/or irinotecan on
      sphere formation. Overall, our results suggest that SC-43 and SC-78 are potent
      STAT3 inhibitors that may potentially be used in combination therapy for CRC.

PMID- 30109145
TI  - Selection and evaluation of an efficient method for the recovery of viral nucleic
      acid extraction from complex biologicals.
AB  - There is a need for a broad and efficient testing strategy for the detection of
      both known and novel viral adventitious agents in vaccines and biologicals. High
      throughput sequencing (HTS) is an approach for such testing; however, an
      optimized testing method is one with a sample-processing pipeline that can help
      detect any viral adventitious agent that may be present. In this study, 11
      commercial methods were assessed for efficient extraction of nucleic acids from a
      panel of viruses. An extraction strategy with two parallel arms, consisting of
      both the Invitrogen PureLinkTM Virus RNA/DNA kit for total nucleic acid
      extraction and the Wako DNA Extractor(r) kit with an RNase A digestion for
      enrichment of double-stranded nucleic acid, was selected as the strategy for the
      extraction of all viral nucleic acid types (ssRNA, dsRNA, and dsDNA). Downstream
      processes, such as double-strand DNA synthesis and whole-genome amplification
      (WGA), were also assessed for the retrieval of viral sequences. Double-stranded
      DNA synthesis yielded larger numbers of viral reads, whereas WGA exhibited a
      strong bias toward amplification of double-stranded DNA, including host cellular
      DNA. The final sample-processing strategy consisted of the dual extraction
      approach followed by double-stranded DNA synthesis, which yielded a viral
      population with increased detection of some viruses by 8600-fold. Here we
      describe an efficient extraction procedure to support viral adventitious agent
      detection in cell substrates used for biological products using HTS.

PMID- 30109146
TI  - Nocturnal penile erections: A retrospective study of the role of RigiScan in
      predicting the response to sildenafil in erectile dysfunction patients.
AB  - Sildenafil enhances the nitric oxide-cGMP pathway of erection, which is claimed
      to have a role in nocturnal penile tumescence and rigidity (NPTR). This study
      aimed to find whether RigiScan can predict the response to sildenafil among
      erectile dysfunction (ED) patients and to find which RigiScan parameter produces
      the best prediction. Medical records of 172 ED patients were revised regarding
      their full sexual history, standard andrology examination, NPTR monitoring by the
      RigiScan device, and the degree of response to sildenafil. Of 172 ED patients, 94
      patients (54.7%) were sildenafil responders. All RigiScan parameters were higher
      in the sildenafil responder group. The RigiScan parameters with the most
      differentiating power between both sildenafil responders and non-responders were
      base rigidity (AUC 0.860) and then tip rigidity (AUC 0.831). The cut-off value of
      base and tip rigidity with the highest diagnostic accuracy was 42.5%. This
      finding was found to be more specific than the sensitivity in predicting a
      positive response to sildenafil (85.9% vs. 70.2% and 92.3% vs. 59.6%, for base
      and tip rigidity, respectively). Sildenafil response in ED cases can be predicted
      through NPTR monitoring using the RigiScan device and ED patients with RigiScan
      base or tip rigidity less than 42% are not expected to respond well to
      sildenafil.

PMID- 30109148
TI  - Use of Robots as a Creative Approach in Healthcare ICT.

PMID- 30109149
TI  - Safety and Usability Guidelines of Clinical Information Systems Integrating
      Clinical Workflow: A Systematic Review.
AB  - Objectives: The usability of clinical information systems (CISs) is known to be
      an essential consideration in ensuring patient safety as well as integrating
      clinical flow. This study aimed to determine how usability and safety guidelines
      of CIS consider clinical workflow through a systematic review in terms of the
      target systems, methodology, and guideline components of relevant articles.
      Methods: A literature search was conducted for articles published from 2000 to
      2015 in PubMed, Cochrane, EMBASE, Web of Science, and CINAHL. The Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement
      method was employed. Articles containing recommendations, principles, and
      evaluation items for CIS usability and safety were included. The selected
      articles were classified according to article type, methodology, and target
      systems. Taking clinical workflow into consideration, the components of
      guidelines were extracted and classified. Results: A total of 7,401 articles were
      identified by keyword search. From the 76 articles remaining after abstract
      screening, 15 were selected through full-text review. Literature review (n = 7)
      was the most common methodology, followed by expert opinions (n = 6).
      Computerized physician order entry (n = 6) was the most frequent system. Four
      articles considered the entire process of clinical tasks, and two articles
      considered the principles of the entire process of user interface affecting
      clinical workflow. Only two articles performed heuristic evaluations of CISs.
      Conclusions: The usability and safety guidelines of CISs need improvement in
      guideline development methodology and with consideration of clinical workflow.

PMID- 30109150
TI  - Fast Convolutional Method for Automatic Sleep Stage Classification.
AB  - Objectives: Polysomnography is essential to diagnose sleep disorders. It is used
      to identify a patient's sleep pattern during sleep. This pattern is obtained by a
      doctor or health practitioner by using a scoring process, which is time
      consuming. To overcome this problem, we developed a system that can automatically
      classify sleep stages. Methods: This paper proposes a new method for sleep stage
      classification, called the fast convolutional method. The proposed method was
      evaluated against two sleep datasets. The first dataset was obtained from
      physionet.org, a physiologic signals data centers. Twenty-five patients who had a
      sleep disorder participated in this data collection. The second dataset was
      collected in Mitra Keluarga Kemayoran Hospital, Indonesia. Data was recorded from
      ten healthy respondents. Results: The proposed method reached 73.50% and 56.32%
      of the F-measures for the PhysioNet and Mitra Keluarga Kemayoran Hospital data,
      respectively. Both values were the highest among all the machine learning methods
      considered in this study. The proposed method also had an efficient running time.
      The fast convolutional models of the PhysioNet and Mitra Keluarga Kemayoran
      Hospital data needed 42.60 and 0.06 seconds, respectively. Conclusions: The fast
      convolutional method worked well on the tested datasets. It achieved a high F
      measure result and an efficient running time. Thus, it can be considered a
      promising tool for sleep stage classification.

PMID- 30109147
TI  - A review on the use of magnetic fields and ultrasound for non-invasive cancer
      treatment.
AB  - Current popular cancer treatment options, include tumor surgery, chemotherapy,
      and hormonal treatment. These treatments are often associated with some inherent
      limitations. For instances, tumor surgery is not effective in mitigating
      metastases; the anticancer drugs used for chemotherapy can quickly spread
      throughout the body and is ineffective in killing metastatic cancer cells.
      Therefore, several drug delivery systems (DDS) have been developed to target
      tumor cells, and release active biomolecule at specific site to eliminate the
      side effects of anticancer drugs. However, common challenges of DDS used for
      cancer treatment, include poor site-specific accumulation, difficulties in
      entering the tumor microenvironment, poor metastases and treatment efficiency. In
      this context, non-invasive cancer treatment approaches, with or without DDS,
      involving the use of light, heat, magnetic field, electrical field and ultrasound
      appears to be very attractive. These approaches can potentially improve treatment
      efficiency, reduce recovery time, eliminate infections and scar formation. In
      this review we focus on the effects of magnetic fields and ultrasound on cancer
      cells and their application for cancer treatment in the presence of drugs or DDS.

PMID- 30109151
TI  - Temporal Segmentation for Capturing Snapshots of Patient Histories in Korean
      Clinical Narrative.
AB  - Objectives: Clinical discharge summaries provide valuable information about
      patients' clinical history, which is helpful for the realization of intelligent
      healthcare applications. The documents tend to take the form of separate segments
      based on temporal or topical information. If a patient's clinical history can be
      seen as a consecutive sequence of clinical events, then each temporal segment can
      be seen as a snapshot, providing a certain clinical context at a specific moment.
      This study aimed to demonstrate a temporal segmentation method of Korean clinical
      narratives for identifying textual snapshots of patient history as a proof-of-a
      concept. Methods: Our method uses pattern-based segmentation to approximate human
      recognition of the temporal or topical shifts in clinical documents. We utilized
      rheumatic patients' discharge summaries and transformed them into sequences of
      constituent chunks. We built 97 single pattern functions to denote whether a
      certain chunk has attributes that indicate that it can be a segment boundary. We
      manually defined the relationships between the pattern functions to resolve
      multiple pattern matchings and to make a final decision. Results: The algorithm
      segmented 30 discharge summaries and processed 1,849 decision points. Three human
      judges were asked whether they agreed with the algorithm's prediction, and the
      agreement percentage on the judges' majority opinion was 89.61%. Conclusions:
      Although this method is based on manually constructed rules, our findings
      demonstrate that the proposed algorithm can achieve fairly good segmentation
      results, and it may be the basis for methodological improvement in the future.

PMID- 30109152
TI  - Self-management of Chronic Conditions Using mHealth Interventions in Korea: A
      Systematic Review.
AB  - Objectives: Population aging has increased the burden of chronic diseases
      globally. mHealth is often cited as a viable solution to enhance the management
      of chronic conditions. In this study, we conducted a systematic review of mHealth
      interventions for the self-management of chronic diseases in Korea, a highly
      connected country with a high chronic care burden. Methods: Five databases were
      searched for relevant empirical studies that employed randomized controlled trial
      (RCT) or quasi-experimental methods published in English or Korean from the years
      2008 to 2018. The selected studies were reviewed according to the PRISMA
      guidelines. The selected studies were classified using the Individual and Family
      Self-Management Theory conceptual framework. Results: Sixteen studies met the
      inclusion criteria, 9 of which were targeted towards diabetes management, and 7
      of which were RCTs. Other target diseases included hypertension, stroke, asthma,
      and others. mHealth interventions were primarily delivered through smartphone
      applications, mobile phones connected to a monitoring device, and short message
      services (SMS). Various self-management processes were applied, including
      providing social influence and support, and facilitating self-monitoring and goal
      setting. Eleven studies showed mHealth interventions to be effective in improving
      self-management behaviors, biomarkers, or patient-reported outcome measures
      associated with chronic diseases. Conclusions: While the number of identified
      studies was not large, none reported negative impacts of mHealth on selected
      outcomes. Future studies on mHealth should design interventions with a greater
      variety of targeted functions and should adopt more rigorous methodologies to
      strengthen the evidence for its effectiveness in chronic disease management.

PMID- 30109153
TI  - Electrocardiogram Sampling Frequency Range Acceptable for Heart Rate Variability
      Analysis.
AB  - Objectives: Heart rate variability (HRV) has gained recognition as a noninvasive
      marker of autonomic activity. HRV is considered a promising tool in various
      clinical scenarios. The optimal electrocardiogram (ECG) sampling frequency
      required to ensure sufficient precision of R-R intervals for HRV analysis has not
      yet been determined. Here, we aimed to determine the acceptable ECG sampling
      frequency range by analyzing ECG signals from patients who visited an emergency
      department with the chief complaint of acute intoxication or overdose. Methods:
      The study included 83 adult patients who visited an emergency department with the
      chief complaint of acute poisoning. The original 1,000-Hz ECG signals were down
      sampled to 500-, 250-, 100-, and 50-Hz sampling frequencies with linear
      interpolation. R-R interval data were analyzed for time-domain, frequency-domain,
      and nonlinear HRV parameters. Parameters derived from the data on down-sampled
      frequencies were compared with those derived from the data on 1,000-Hz signals,
      and Lin's concordance correlation coefficients were calculated. Results: Down
      sampling to 500 or 250 Hz resulted in excellent concordance. Signals down-sampled
      to 100 Hz produced acceptable results for time-domain analysis and Poincare
      plots, but not for frequency-domain analysis. Down-sampling to 50 Hz proved to be
      unacceptable for both time- and frequency-domain analyses. At 50 Hz, the root
      mean-squared successive differences and the power of high frequency tended to
      have high values and random errors. Conclusions: A 250-Hz sampling frequency
      would be acceptable for HRV analysis. When frequency-domain analysis is not
      required, a 100-Hz sampling frequency would also be acceptable.

PMID- 30109154
TI  - Effectiveness of Mobile Health Application Use to Improve Health Behavior
      Changes: A Systematic Review of Randomized Controlled Trials.
AB  - Objectives: The purpose of this study was to examine the effectiveness of mobile
      health applications in changing health-related behaviors and clinical health
      outcomes. Methods: A systematic review was conducted in this study. We conducted
      a comprehensive bibliographic search of articles on health behavior changes
      related to the use of mobile health applications in peer-reviewed journals
      published between January 1, 2000 and May 31, 2017. We used databases including
      CHINAHL, Ovid-Medline, EMBASE, and PubMed. The risk of bias assessment of the
      retrieved articles was examined using the Scottish Intercollegiate Guidelines
      Network. Results: A total of 20 articles met the inclusion criteria. Sixteen
      among 20 studies reported that applications have a positive impact on the
      targeted health behaviors or clinical health outcomes. In addition, most of the
      studies, which examined the satisfaction of participants, showed health app users
      have a statistically significant higher satisfaction. Conclusions: Despite the
      high risk of bias, such as selection, performance, and detection, this systematic
      review found that the use of mobile health applications has a positive impact on
      health-related behaviors and clinical health outcomes. Application users were
      more satisfied with using mobile health applications to manage their health in
      comparison to users of conventional care.

PMID- 30109155
TI  - Classification of Iris Colors and Patterns in Koreans.
AB  - Objectives: The iris is the part of the eye that is colored, and it is an
      important feature in making an artificial eye. To address the lack of information
      about the brown Korean irises, we classified the colors and patterns of the
      irises of 100 Korean eyes. Methods: The iris colors were extracted from 100
      different digital photographs of each eye using K-mean clustering image analysis.
      The RGB data of the extracted colors were converted to CIELAB color space data
      and analyzed to determine the representative color of the iris in each
      photograph. The color differences were calculated to form groups of similar
      colors by matching the 100 samples into several groups with minimum color
      differences among them. The average hue value for each group was calculated, and
      the corresponding representative color was selected from 2 to 3 colors in one
      group. Results: The iris colors were classified into seven brown color groups
      with 2 to 3 colors in each group. The coloration of Koreans' eyes appears to vary
      in a similar hue with differences in chroma and lightness. In addition, the iris
      patterns were classified into three basic patterns, namely, crown, sunshine, and
      flower, as well as three complex patterns that are mixtures of two basic
      patterns. Conclusions: We classified Korean iris colors and patterns for
      application in the design of artificial eyes.

PMID- 30109156
TI  - Application of Convolutional Neural Network in the Diagnosis of Jaw Tumors.
AB  - Objectives: Ameloblastomas and keratocystic odontogenic tumors (KCOTs) are
      important odontogenic tumors of the jaw. While their radiological findings are
      similar, the behaviors of these two types of tumors are different. Precise
      preoperative diagnosis of these tumors can help oral and maxillofacial surgeons
      plan appropriate treatment. In this study, we created a convolutional neural
      network (CNN) for the detection of ameloblastomas and KCOTs. Methods: Five
      hundred digital panoramic images of ameloblastomas and KCOTs were retrospectively
      collected from a hospital information system, whose patient information could not
      be identified, and preprocessed by inverse logarithm and histogram equalization.
      To overcome the imbalance of data entry, we focused our study on 2 tumors with
      equal distributions of input data. We implemented a transfer learning strategy to
      overcome the problem of limited patient data. Transfer learning used a 16-layer
      CNN (VGG-16) of the large sample dataset and was refined with our secondary
      training dataset comprising 400 images. A separate test dataset comprising 100
      images was evaluated to compare the performance of CNN with diagnosis results
      produced by oral and maxillofacial specialists. Results: The sensitivity,
      specificity, accuracy, and diagnostic time were 81.8%, 83.3%, 83.0%, and 38
      seconds, respectively, for the CNN. These values for the oral and maxillofacial
      specialist were 81.1%, 83.2%, 82.9%, and 23.1 minutes, respectively. Conclusions:
      Ameloblastomas and KCOTs could be detected based on digital panoramic
      radiographic images using CNN with accuracy comparable to that of manual
      diagnosis by oral maxillofacial specialists. These results demonstrate that CNN
      may aid in screening for ameloblastomas and KCOTs in a substantially shorter
      time.

PMID- 30109157
TI  - Construction of an Electrocardiogram Database Including 12 Lead Waveforms.
AB  - Objectives: Electrocardiogram (ECG) data are important for the study of
      cardiovascular disease and adverse drug reactions. Although the development of
      analytical techniques such as machine learning has improved our ability to
      extract useful information from ECGs, there is a lack of easily available ECG
      data for research purposes. We previously published an article on a database of
      ECG parameters and related clinical data (ECG-ViEW), which we have now updated
      with additional 12-lead waveform information. Methods: All ECGs stored in
      portable document format (PDF) were collected from a tertiary teaching hospital
      in Korea over a 23-year study period. We developed software which can extract all
      ECG parameters and waveform information from the ECG reports in PDF format and
      stored it in a database (meta data) and a text file (raw waveform). Results: Our
      database includes all parameters (ventricular rate, PR interval, QRS duration,
      QT/QTc interval, P-R-T axes, and interpretations) and 12-lead waveforms (for
      leads I, II, III, aVR, aVL, aVF, V1, V2, V3, V4, V5, and V6) from 1,039,550 ECGs
      (from 447,445 patients). Demographics, drug exposure data, diagnosis history, and
      laboratory test results (serum calcium, magnesium, and potassium levels) were
      also extracted from electronic medical records and linked to the ECG information.
      Conclusions: Electrocardiogram information that includes 12 lead waveforms was
      extracted and transformed into a form that can be analyzed. The description and
      programming codes in this case report could be a reference for other researchers
      to build ECG databases using their own local ECG repository.

PMID- 30109158
TI  - National Healthcare Service and Its Big Data Analytics.

PMID- 30109159
TI  - Correction: Using Statistical and Machine Learning Methods to Evaluate the
      Prognostic Accuracy of SIRS and qSOFA.
AB  - [This corrects the article on p. 139 in vol. 24, PMID: 29770247.].

PMID- 30109160
TI  - A peptide containing the receptor binding site of insulin-like growth factor
      binding protein-2 enhances bone mass in ovariectomized rats.
AB  - Male Igfbp2-/- mice have a significant reduction in bone mass and administration
      of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP
      2) receptor-binding domain stimulates bone formation in these animals. Female
      Igfbp2-/- mice do not have this phenotype but following ovariectomy (OVX) lose
      more bone than OVX wild-type mice. This suggests that in the absence of estrogen,
      IGFBP-2 is required to maintain bone mass. Therefore these studies were
      undertaken to determine if this peptide could stimulate bone acquisition in OVX
      rats. OVX rats were divided into seven treatment groups: sham animals, OVX
      animals, OVX animals receiving a control scrambled peptide, or one of three doses
      of the active peptide termed PEG-HBD-1 (0.7, 2, and 6 mg.kg-1) and an OVX group
      receiving parathyroid hormone (PTH) (50 ug.kg-1 per day). The peptides were
      administered for 8 weeks. DXA revealed a significant reduction in femoral and
      tibial areal bone mineral density (aBMD) after OVX, whereas treatment with the
      high-dose peptide increased aBMD by 6.2% +/- 2.4% (P < 0.01) compared to control
      peptide; similar to the increase noted with PTH (5.6% +/- 3.0%, P < 0.01).
      Similar increases were noted with two lower doses of the peptide (3.8% +/- 1.5%,
      P < 0.05 for low dose; 3.1% +/- 1.6%, P = 0.07 for middle dose). Micro CT showed
      that the OVX control peptide animals had reductions of 41% and 64% in femoral
      trabecular BV/TV and trabecular number, respectively. All three doses of the
      peptide increased bone volume/total volume (BV/TV) significantly, while the low
      and middle doses increased trabecular number. Cortical BV/TV and thickness at the
      midshaft increased significantly with each dose of peptide (18.9% +/- 9.8%, P <
      0.01 and 14.2% +/- 7.9%, P < 0.01 for low dose; 23.7% +/- 10.7%, P < 0.001 and
      15.8% +/- 6.1%, P < 0.001 for middle dose; 19.0% +/- 6.9%, P < 0.01 and 16.2% +/-
      9.7%, P < 0.001 for high dose) and with PTH (25.8% +/- 9.2%, P < 0.001 and 19.4%
      +/- 8.8%, P < 0.001). Histomorphometry showed that the lowest dose of peptide
      stimulated BV/TV, trabecular thickness, mineral apposition rate (MAR), bone
      formation rate/bone surface (BFR/BS), number of osteoblasts/bone perimeter
      (N.ob/B.pm), and decreased osteoclast surface/bone perimeter (Oc.S/B.Pm). The
      highest dose stimulated each of these parameters except MAR and BFR/BS. Thus, the
      heparin-binding domain receptor region of IGFBP-2 accounts for its anabolic
      activity in bone. Importantly, this peptide enhances bone mass in estrogen
      deficient animals.

PMID- 30109162
TI  - Malignant Pleural Mesothelioma, Biphasic Type: An Unusual and Insidious Case of
      Rapidly Progressive Small Blue Cell Tumor.
AB  - Malignant pleural mesothelioma (MPM) is a rare neoplasm. It predominantly affects
      elderly individuals aged over 70 years presenting with a unilateral pleural tumor
      usually associated with previous asbestos exposure. The respiratory symptoms are
      associated with ipsilateral pleural involvement with concomitant pleural
      effusions. The diagnosis of MPM is established by the morphologic and
      immunohistochemical features of a cytologic specimen. MPM can present as three
      histologic subtypes: epithelioid, sarcomatoid, or biphasic. We present a case of
      an 85-year-old Caucasian female with a history of occupational asbestos exposure.
      She complained of 1-week history of progressive sharp right flank and scapular
      pain with mild shortness of breath, dry cough and pleuritic chest pain. CT of the
      chest showed a large loculated right pleural effusion with adjacent pleural
      thickening. CT abdomen and pelvis was negative for other neoplastic findings. CT
      guided core biopsy of the right pleural-based mass was positive for a spindle to
      plasmacytoid small blue cell tumor. An extensive immunohistochemical panel was
      non-specific. A focal OSCAR keratin and WT-1 expression in the absence of
      carcinoma markers, a malignant mesothelioma, biphasic type was diagnosed. Further
      workup with PET-CT and cytotoxic chemotherapy combined with immunotherapy or
      tyrosine kinase inhibitors was recommended by oncology. The patient refused
      further imaging and treatment, and palliative care was consulted.

PMID- 30109161
TI  - Measuring Geographic and Wealth Inequalities in Health Distribution as Tools for
      Identifying Priority Health Inequalities and the Underprivileged Populations.
AB  - Background: Currently, there is no consensus on standard measure that can be
      routinely part of the health information systems to alert countries to
      inequalities in health and identify the priority health inequality conditions.
      Objectives: To identify the health inequality measures relevant for assessing
      geographic and wealth inequalities; use the measures as a demonstration to what
      can happen in practice to recognize the geographic and wealth-related priority
      health inequalities within a country; and identify the geographic and wealth
      underprivileged populations. Method: Egypt data were used as demonstration.
      Pearson coefficient of correlation was calculated to compare the various
      geographic and wealth health inequality measures. T test was used to identify
      significant correlations. The relevant inequality measures were used to rank
      geographic and wealth health inequalities and identify the underprivileged
      populations. Results: The wealth inequalities in health measured by the
      concentration index provide a familiar and perform adequately in identifying
      economic inequalities in health. However, the geographic health inequalities
      identified by the index of dissimilarity appear to provide a more comprehensive
      profile of health inequalities within a country. Conclusion: There is a need for
      a feasible inequality measure in the health information systems. A country's
      geographic health distribution measured by the index of dissimilarity appears to
      provide a feasible first-step alarm to inform and guide the uptake of equity
      sensitive policies.

PMID- 30109163
TI  - Can Overuse of Kambo Cause Psychosis?
AB  - Kambo is an emerging ritual, which involves the application of the toxin produced
      by Phyllomedusa bicolor to a freshly burnt area to heal chronic diseases of the
      mind and body. Due to the widespread use of kambo, more cases of symptomatic
      health conditions are being discovered. In this case study, we report a patient
      with psychosis potentially due to the kambo ritual.

PMID- 30109164
TI  - Non-traumatic Retinal Detachment Diagnosed via Bedside Ultrasonography.
AB  - The authors report a case of an elderly patient with left eye retinal detachment
      who presented to the emergency department (ED). Bedside ultrasonography of the
      retina revealed a hyperechoic, smooth, folded membrane within the vitreous,
      consistent with a diagnosis of retinal detachment. Ophthalmological consultation
      was obtained, and the patient healed well after surgical repair.

PMID- 30109165
TI  - Diabetic Hand: A Neglected Complication of Diabetes Mellitus.
AB  - Diabetes mellitus is associated with a variety of musculoskeletal (MSK)
      manifestations affecting the hand, which can significantly affect a patient's
      quality of life. While a great deal of attention is paid to the chronic
      microvascular complications of diabetes, the MSK complications are often ignored
      in clinical practice. It is important to diagnose them as their presence has been
      found to correlate with chronic microvascular complications of diabetes
      especially retinopathy. We describe a case of a young male with long-standing
      type 1 diabetes mellitus and chronic microvascular complications, who presented
      to us with several manifestations of diabetic hand syndrome.

PMID- 30109166
TI  - Evaluation of Information Sources in Plastic Surgery Decision-making.
AB  - Background Today, patients can access a myriad of information sources regarding
      plastic surgery procedures prior to meeting with a surgeon. Despite their
      widespread use, the role of these sources in a patient's decision-making remains
      undefined. We hypothesized that the physician remains the key information source
      for patients making surgical decisions in plastic surgery, but that other sources
      may deliver important insights and prove helpful to varying degrees. We also
      explored motivations for this outside information search and any differences in
      perceived value among patients. Methods We administered a survey regarding
      various information sources to our breast reconstruction, reduction, and
      abdominoplasty patients. Responses were compared between surgery groups and
      demographic groups. Ordinal logistic regression analysis was used to determine
      the impact of patient characteristics on helpfulness rank of different sources.
      Results Survey results were obtained from 58 patients, of whom 10 (17.2%) had
      abdominoplasty, 35 (60.3%) breast reconstruction, and 13 (22.4%) breast
      reduction. The most popular information sources prior to the first surgical
      appointment were Internet searches (56.9%) and family/friends/other patients
      (39.7%). After the initial appointment, the most useful sources were plastic
      surgeons (84.5%), and the Internet (36.2%). Most patients (73.5%) still sought
      outside information after their appointment. On a Likert-type scale of
      helpfulness, plastic surgeons ranked 4.28/5, followed by the web-based patient
      education platform, 3.73 and the Internet, 3.6. A total of 63% of participants
      listed plastic surgeons as their single most important source of information. In
      ordinal logistic regression analysis, non-white race was significantly associated
      with higher rank of surgeon helpfulness (p < 0.05). Relative to low-income
      patients, income $50-100k (p < 0.05) and $100k+ (p < 0.05) were associated with
      lower rank of surgeon helpfulness. Conclusions Most patients seek outside
      information prior to visiting with a surgeon from the Internet, social media, or
      family and friends. Patients consider plastic surgeons their most valuable
      information source overall, though still in need of supplementation for varying
      reasons. Additionally, certain demographic differences affect patient perception
      of information sources, and this is an important factor for surgeons to consider
      as they approach educating patients.

PMID- 30109167
TI  - An Unusual Variation of the Accessory Nerve.
AB  - The accessory nerve is an important nerve in the head and neck regions. Some
      variants of this nerve's anatomy have been reported. Herein, we present an
      unusual report and review the extant medical literature regarding other more
      commonly found derailments of this nerve's anatomy.

PMID- 30109168
TI  - Pelvic Kidney: A Review of the Literature.
AB  - Kidney development is a complex process that begins during the sixth to eighth
      weeks of life. Failure of ascent of the kidney will cause the kidney to remain in
      the pelvis i.e., pelvic kidney. Here, we review this entity in detail and
      illustrate such embryological derailment. In most cases, a pelvic kidney is an
      incidental finding and is usually asymptomatic. Anatomic variations of the renal
      vasculature have been reported in cases of pelvic kidneys and these are
      highlighted in this review. Clinicians who treat patients for renal or pelvic
      disease or interpret images of the pelvis should be well informed of the anatomy
      and embryology of the pelvic kidney.

PMID- 30109169
TI  - Characterisation of the Morphological, Functional and Molecular Changes in
      Sunitinib-Resistant Renal Cell Carcinoma Cells.
AB  - Sunitinib resistance is a major clinical problem hampering the treatment of renal
      cell carcinoma (RCC). Studies on the comprehensive characterisation of
      morphological, functional and molecular changes in sunitinib-resistant RCC cells
      are lacking. The aim of the current study was to develop sunitinib resistance in
      four human RCC cell lines (786-0, Caki-1, Caki-2 and SN12K1), and to characterise
      the changed cell biology with sunitinib resistance. RCC cells were made resistant
      by continuous, chronic exposure to 10 MUM of sunitinib over a period of 12
      months. Cell proliferation, morphology, transmigration, and gene expression for
      interleukin-6 (IL-6), interleukin-8 (IL-8), vascular endothelial growth factor
      (VEGF), Bcl-2 and Bax were studied. There was no significant difference in growth
      rate or transmigration between the parental and resistant cells. Sunitinib
      resistant cells were significantly hypertrophic compared with parental cells as
      evidenced by increases in the surface areas of the whole cells and the nuclei. IL
      6 was significantly increased in all resistant cells. IL-8 was increased in
      sunitinib-resistant Caki-2 and SN12K1 cells and decreased in 786-0 without any
      significant changes in Caki-1. VEGF was increased in resistant Caki-2 and SN12K1
      cells but not in 786-0 and Caki-1. The Bcl2/Bax ratio was increased in Caki-1,
      Caki-2 and SN12K1 cells but decreased in 786-0 cells. The increased IL-6 may
      contribute to sunitinib resistance either via VEGF-mediated angiogenesis or
      through shifting of the Bcl2/Bax balance in favour of anti-apoptosis.

PMID- 30109171
TI  - Age restriction warning label efficacy and high school student consumption of
      highly-caffeinated products.
AB  - Age restriction warning labels (ARLs) are placed on highly-caffeinated food and
      drinks, such as Red Bull, to deter consumption by minors who are especially
      vulnerable to the risks of excessive caffeine consumption. Previous studies have
      shown that ARLs on media like TV programs and video games fail to discourage
      minors. However, it is unclear how ARLs on food and drink packages affect minors'
      purchasing behavior. High school students aged 14 to 17 years (n = 150, Mage =
      15.2, 51% male) were asked to choose between seven novel product dyads (three
      food/drink dyads, two movie dyads, and two video game dyads); each dyad contained
      one product with an ARL and one without. Participants were then asked how ARLs
      and parental permissiveness of ARL products influenced their decision. Roughly
      half of the participants selected food and drink products with ARLs. Over two
      thirds (69%) of the students reported that they were not discouraged by ARLs on
      highly caffeinated food and drinks. Participants reported their parents as
      significantly less permissive of age-restricted food and drink products than of
      age-restricted media merchandise (p < .01). Perceived parental permissiveness was
      not correlated with minors' perception of ARL or simulated product choice.
      Current ARLs on highly caffeinated food and drink items may be ineffective for
      adolescents and may actually increase product appeal. Pediatricians should
      educate patients and parents regarding the health risks of excessive caffeine
      consumption.

PMID- 30109173
TI  - Editor Profiles: Guest Editor of Special Column on Targeted Cancer Therapy.

PMID- 30109172
TI  - Predicting which type of push notification content motivates users to engage in a
      self-monitoring app.
AB  - Despite the unprecedented access to self-monitoring health apps, lack of optimal
      user engagement remains a significant challenge. Push notification prompts with
      contextually tailored messages offers a promising strategy to improve engagement.
      To increase the efficacy of push-notifications on engaging individuals with
      health apps, greater attention to the modifiable components of push notifications
      that influence responsiveness is needed. This study examines the effect of
      message content and frequency of push notifications, along with past app usage on
      responding to notifications within 24 h, and engaging with self-monitoring in
      JOOL Health smartphone app. Mixed models were applied on a de-identified data set
      of 18,000 contextually tailored push notifications sent by JOOL Health App to
      1414 participants. The content in sent messages on behavioural topics were mapped
      into either tailored suggestions or tailored insights. Our findings suggest that
      push notifications with tailored suggestions were more effective overall in
      encouraging self-monitoring, but amongst frequent app users, push-notifications
      containing insights was associated with greater self-monitoring. People who were
      not using the app as frequently were less likely to respond to a prompt. This
      study suggests that push-notification content does have an impact on subsequent
      use of key app features, and app developers should consider what content is
      likely to work best for who, and under what circumstances. Secondary data
      analysis of commercial apps presents a unique opportunity to elucidate and
      optimize health behaviors.

PMID- 30109170
TI  - Adiposity, fitness, health-related quality of life and the reallocation of time
      between children's school day activity behaviours: A compositional data analysis.
AB  - : Sedentary time (ST), light (LPA), and moderate-to-vigorous physical activity
      (MVPA) constitute the range of school day activity behaviours. This study
      investigated whether the composition of school activity behaviours was associated
      with health indicators, and the predicted changes in health when time was
      reallocated between activity behaviours. Accelerometers were worn for 7-days
      between October and December 2010 by 318 UK children aged 10-11, to provide
      estimates of school day ST, LPA, and MVPA. BMI z-scores and percent waist-to
      height ratio were calculated as indicators of adiposity. Cardiorespiratory
      fitness (CRF) was assessed using the 20-m shuttle run test. The PedsQLTM
      questionnaire was completed to assess psychosocial and physical health-related
      quality of life (HRQL). Log-ratio multiple linear regression models predicted
      health indicators for the mean school day activity composition, and for new
      compositions where fixed durations of time were reallocated from one activity
      behaviour to another, while the remaining behaviours were unchanged. The school
      day activity composition significantly predicted adiposity and CRF (p = 0.04
      0.002), but not HRQL. Replacing MVPA with ST or LPA around the mean activity
      composition predicted higher adiposity and lower CRF. When ST or LPA were
      substituted with MVPA, the relationships with adiposity and CRF were asymmetrical
      with favourable, but smaller predicted changes in adiposity and CRF than when
      MVPA was replaced. Predicted changes in HRQL were negligible. The school day
      activity composition significantly predicted adiposity and CRF but not HRQL.
      Reallocating time from ST and LPA to MVPA is advocated through comprehensive
      school physical activity promotion approaches. Trial registration:
      ISRCTN03863885.

PMID- 30109174
TI  - Editorial Preface for Targeted Cancer Therapy.

PMID- 30109176
TI  - Targeting an oncogenic kinase/phosphatase signaling network for cancer therapy.
AB  - Protein kinases and phosphatases signal by phosphorylation and dephosphorylation
      to precisely control the activities of their individual and common substrates for
      a coordinated cellular outcome. In many situations, a kinase/phosphatase complex
      signals dynamically in time and space through their reciprocal regulations and
      their cooperative actions on a substrate. This complex may be essential for
      malignant transformation and progression and can therefore be considered as a
      target for therapeutic intervention. p38gamma is a unique MAPK family member that
      contains a PDZ motif at its C-terminus and interacts with a PDZ domain-containing
      protein tyrosine phosphatase PTPH1. This PDZ-coupled binding is required for both
      PTPH1 dephosphorylation and inactivation of p38gamma and for p38gamma
      phosphorylation and activation of PTPH1. Moreover, the p38gamma/PTPH1 complex can
      further regulate their substrates phosphorylation and dephosphorylation, which
      impacts Ras transformation, malignant growth and progression, and therapeutic
      response. This review will use the p38gamma/PTPH1 signaling network as an example
      to discuss the potential of targeting the kinase/phosphatase signaling complex
      for development of novel targeted cancer therapy.

PMID- 30109175
TI  - Understanding the biology of HER3 receptor as a therapeutic target in human
      cancer.
AB  - HER3 belongs to the human epidermal growth factor receptor (HER) family which
      also includes HER1/EGFR/erbB1, HER2/erbB2, and HER4/erbB4. As a unique member of
      the HER family, HER3 lacks or has little intrinsic tyrosine kinase activity. It
      frequently co-expresses and forms heterodimers with other receptor tyrosine
      kinases (RTKs) in cancer cells to activate oncogenic signaling, especially the PI
      3K/Akt pathway and Src kinase. Elevated expression of HER3 has been observed in a
      wide variety of human cancers and associates with a worse survival in cancer
      patients with solid tumors. Studies on the underlying mechanism implicate HER3
      expression as a major cause of treatment failure in cancer therapy. Activation of
      HER3 signaling has also been shown to promote cancer metastasis. These data
      strongly support the notion that therapeutic inactivation of HER3 and/or its
      downstream signaling is required to overcome treatment resistance and improve the
      outcomes of cancer patients.

PMID- 30109177
TI  - Taxane resistance in castration-resistant prostate cancer: mechanisms and
      therapeutic strategies.
AB  - Despite its good initial response and significant survival benefit in patients
      with castration-resistant prostate cancer (CRPC), taxane therapy inevitably
      encounters drug resistance in all patients. Deep understandings of taxane
      resistant mechanisms can significantly facilitate the development of new
      therapeutic strategies to overcome taxane resistance and improve CRPC patient
      survival. Multiple pathways of resistance have been identified as potentially
      crucial areas of intervention. First, taxane resistant tumor cells typically have
      mutated microtubule binding sites, varying tubulin isotype expression, and
      upregulation of efflux transporters. These mechanisms contribute to reducing
      binding affinity and availability of taxanes. Second, taxane resistant tumors
      have increased stem cell like characteristics, indicating higher potential for
      further mutation in response to therapy. Third, the androgen receptor pathway is
      instrumental in the proliferation of CRPC and multiple hypotheses leading to this
      pathway reactivation have been reported. The connection of this pathway to the
      AKT pathway has received significant attention due to the upregulation of
      phosphorylated AKT in CRPC. This review highlights recent advances in elucidating
      taxane resistant mechanisms and summarizes potential therapeutic strategies for
      improved treatment of CRPC.

PMID- 30109178
TI  - Personalized medicine in non-small cell lung cancer: a review from a
      pharmacogenomics perspective.
AB  - Non-small cell lung cancer is a prevalent and rapidly-expanding challenge to
      modern medicine. While generalized medicine with traditional chemotherapy yielded
      comparatively poor response rates and treatment results, the cornerstone of
      personalized medicine using genetic profiling to direct treatment has exalted the
      successes seen in the field and raised the standard for patient treatment in lung
      and other cancers. Here, we discuss the current state and advances in the field
      of personalized medicine for lung cancer, reviewing several of the mutation
      targeting strategies that are approved for clinical use and how they are guided
      by patient genetic information. These classes include inhibitors of tyrosine
      kinase (TKI), anaplastic lymphoma kinase (ALK), and monoclonal antibodies.
      Selecting from these treatment plans and determining the optimal dosage requires
      in-depth genetic guidance with consideration towards not only the underlying
      target genes but also other factors such as individual metabolic capability and
      presence of resistance-conferring mutations both directly on the target gene and
      along its cascade(s). Finally, we provide our viewpoints on the future of
      personalized medicine in lung cancer, including target-based drug combination,
      mutation-guided drug design and the necessity for data of population genetics, to
      provide rough guidance on treating patients who are unable to get genetic
      testing.

PMID- 30109180
TI  - Targeting ERK, an Achilles' Heel of the MAPK pathway, in cancer therapy.
AB  - The mitogen-activated protein kinases (MAPK) pathway, often known as the RAS-RAF
      MEK-ERK signal cascade, functions to transmit upstream signals to its downstream
      effectors to regulate physiological process such as cell proliferation,
      differentiation, survival and death. As the most frequently mutated signaling
      pathway in human cancer, targeting the MAPK pathway has long been considered a
      promising strategy for cancer therapy. Substantial efforts in the past decades
      have led to the clinical success of BRAF and MEK inhibitors. However, the
      clinical benefits of these inhibitors are compromised by the frequently occurring
      acquired resistance due to cancer heterogeneity and genomic instability. This
      review briefly introduces the key protein kinases involved in this pathway as
      well as their activation mechanisms. We also generalize the correlations between
      mutations of MAPK members and human cancers, followed by a summarization of
      progress made on the development of small molecule MAPK kinases inhibitors. In
      particular, this review highlights the potential advantages of ERK inhibitors in
      overcoming resistance to upstream targets and proposes that targeting ERK kinase
      may hold a promising prospect for cancer therapy.

PMID- 30109179
TI  - The application of CAR-T cell therapy in hematological malignancies: advantages
      and challenges.
AB  - Chimeric antigen receptor T cell (CAR-T cell) therapy is a novel adoptive
      immunotherapy where T lymphocytes are engineered with synthetic receptors known
      as chimeric antigen receptors (CAR). The CAR-T cell is an effector T cell that
      recognizes and eliminates specific cancer cells, independent of major
      histocompatibility complex molecules. The whole procedure of CAR-T cell
      production is not well understood. The CAR-T cell has been used predominantly in
      the treatment of hematological malignancies, including acute lymphoblastic
      leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid
      tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T
      cell research and development. CD19 CAR-T cell is most commonly used, and other
      targets, including CD20, CD30, CD38 and CD138 are being studied. Although this
      novel therapy is promising, there are several disadvantages. In this review we
      discuss the applications of CAR-T cells in different hematological malignancies,
      and pave a way for future improvement on the effectiveness and persistence of
      these adoptive cell therapies.

PMID- 30109181
TI  - Olmutinib (HM61713) reversed multidrug resistance by inhibiting the activity of
      ATP-binding cassette subfamily G member 2 in vitro and in vivo.
AB  - Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause
      of multidrug resistance (MDR), which is a significant hurdle to the success of
      chemotherapy in many cancers. Therefore, inhibiting the activity of ABC
      transporters may be a logical approach to circumvent MDR. Olmutinib is an
      epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which
      has been approved in South Korea for advanced EGFR T790M-positive non-small cell
      lung cancer (NSCLC). Here, we found that olmutinib significantly increased the
      sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore,
      olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine
      123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing
      cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit
      photolabeling of ABCG2 with [125I]-iodoarylazidoprazosin (IAAP). However,
      olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked
      EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced
      the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth.
      All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to
      ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug
      accumulation. Our findings encouraged to further clinical investigation on
      combination therapy of olmutinib with conventional chemotherapeutic drugs in
      ABCG2-overexpressing cancer patients.

PMID- 30109182
TI  - Garlic-derived compound S-allylmercaptocysteine inhibits hepatocarcinogenesis
      through targeting LRP6/Wnt pathway.
AB  - Whether and how garlic-derived S-allylmercaptocysteine (SAMC) inhibits
      hepatocellular carcinoma (HCC) is largely unknown. In the current study, the role
      of low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) in HCC
      progression and the anti-HCC mechanism of SAMC was examined in clinical sample,
      cell model and xenograft/orthotopic mouse models. We demonstrated that SAMC
      inhibited cell proliferation and tumorigenesis, while induced apoptosis of human
      HCC cells without influencing normal hepatocytes. SAMC directly interacted with
      Wnt-pathway co-receptor LRP6 on the cell membrane. LRP6 was frequently over
      expressed in the tumor tissue of human HCC patients (66.7% of 48 patients) and
      its over-expression only correlated with the over-expression of beta-catenin, but
      not with age, gender, tumor size, stage and metastasis. Deficiency or over
      expression of LRP6 in hepatoma cells could partly mimic or counteract the anti
      tumor properties of SAMC, respectively. In vivo administration of SAMC
      significantly suppressed the growth of Huh-7 xenograft/orthotopic HCC tumor
      without causing undesirable side effects. In addition, stable down-regulation of
      LRP6 in Huh-7 facilitated the anti-HCC effects of SAMC. In conclusion, LRP6 can
      be a potential therapeutic target of HCC. SAMC is a promising specific anti-tumor
      agent for treating HCC subtypes with Wnt activation at the hepatoma cell surface.

PMID- 30109183
TI  - Gold nanorods together with HSP inhibitor-VER-155008 micelles for colon cancer
      mild-temperature photothermal therapy.
AB  - Enhancing the heat-sensitivity of tumor cells provides an alternative solution to
      maintaining the therapeutic outcome of photothermal therapy (PTT). In this study,
      we constructed a therapeutic system, which was composed of methoxy-polyethylene
      glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the
      effect of VER-155008 on the sensitivity of tumor cells to heat, and further
      investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER
      155008- micelles. VER-155008- micelles down-regulate the expression of heat shock
      proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116
      cells treated with VER-155008- micelles under 45  degrees C is equal to that
      treated with high temperature hyperthermia (55  degrees C) in vitro. Furthermore,
      we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the
      tumor site by photoacoustic imaging and fluorescent imaging. In vivo anti-cancer
      evaluation showed that tumor size remarkably decreased (smaller than 100 mm3 or
      vanished) when treated with combing 45  degrees C mild PTT system, which
      contrasted to the tumor size when treated with individual 45  degrees C mild PTT
      (around 500 nm3) or normal saline as control (larger than 2000 nm3). These
      results proved that the VER-155008- micelles can attenuate the heat-resistance of
      tumor cells and enhance the therapeutic outcome of mild-temperature photothermal
      therapy.

PMID- 30109184
TI  - Development of polyvinylpyrrolidone/paclitaxel self-assemblies for breast cancer.
AB  - The goal of this investigation was to develop and demonstrate a
      polymer/paclitaxel self-assembly (PTX-SA) formulation. Polymer/PTX-SAs were
      screened based on smaller size of formulation using dynamic light scattering
      analysis. Additionally, fluorescence microscopy and flow cytometry studies
      exhibited that polyvinylpyrrolidone (PVP)-based PTX-SAs (PVP/PTX-SAs) had
      superior cellular internalization capability in MCF7 and MDA-MB-231 breast cancer
      cells. The optimized PVP/PTX-SAs exhibited less toxicity to human red blood cells
      indicating a suitable formulation for reducing systemic toxicity. The formation
      of PVP and PTX self-assemblies was confirmed using fluorescence quenching and
      transmission electron microscopy which indicated that the PVP/PTX-SAs were
      spherical in shape with an average size range of 53.81 nm as detected by
      transmission electron microscopy (TEM). FTIR spectral analysis demonstrates
      incorporation of polymer and paclitaxel functional groups in PVP/PTX-SAs. Both
      proliferation (MTS) and clonogenic (colony formation) assays were used to
      validate superior anticancer activity of PVP/PTX-SAs in breast cancer cells over
      paclitaxel. Such superior anticancer activity was also demonstrated by
      downregulation of the expression of pro-survival protein (Bcl-xL), upregulation
      of apoptosis-associated proteins (Bid, Bax, cleaved caspase 7, and cleaved PARP)
      and beta-tubulin stabilization. These results support the hypothesis that PVP/PTX
      SAs improved paclitaxel delivery to cancer cells.

PMID- 30109185
TI  - Structure-based design, synthesis, and biological evaluation of novel
      pyrimidinone derivatives as PDE9 inhibitors.
AB  - The pathological processes of Alzheimer's disease and type 2 diabetes mellitus
      have been demonstrated to be linked together. Both PDE9 inhibitors and PPARgamma
      agonists such as rosiglitazone exhibited remarkable preclinical and clinical
      treatment effects for these two diseases. In this study, a series of PDE9
      inhibitors combining the pharmacophore of rosiglitazone were discovered. All the
      compounds possessed remarkable affinities towards PDE9 and four of them have the
      IC50 values <5 nmol/L. In addition, these four compounds showed low cell toxicity
      in human SH-SY5Y neuroblastoma cells. Compound 11a, the most effective one, gave
      the IC50 of 1.1 nmol/L towards PDE9, which is significantly better than the
      reference compounds PF-04447943 and BAY 73-6691. The analysis of putative binding
      patterns and binding free energy of the designed compounds with PDE9 may explain
      the structure-activity relationships and provide evidence for further structural
      modifications.

PMID- 30109186
TI  - Synthesis and biological evaluation of novel tricyclic matrinic derivatives as
      potential anti-filovirus agents.
AB  - Twenty-six novel tricyclic sophoridinic and matrinic derivatives containing a
      common chlorinated benzene fragment were designed, synthesized and evaluated for
      their anti-ebolavirus (EBOV) activities. Structure-activity relationship analysis
      indicated: (i) 12N-dichlorobenzyl motif was beneficial for the activity; (ii) the
      chiral configuration at C5 atom might not affect the activity much. Among the
      target compounds, compound 7d exhibited the most potent potency against EBOV with
      an IC50 value of 5.29 MUmol/L and an SI value of over 37.8. Further in vivo anti
      EBOV assay of 7d identified its high effectiveness, and in vivo anti-MARV assay
      of 7d suggested its inspiring broad-spectrum anti-filovirus activity. The results
      provided powerful information on further strategic optimization and development
      of this kind of compounds against filoviruses.

PMID- 30109187
TI  - Limonoids from seeds of Azadirachta indica A. Juss. and their cytotoxic activity.
AB  - Four new limonoid-type nortriterpenoids, 1-detigloyl-1-O-methacryloylsalannin
      (1), 28-deoxo-2,3-dihydronimbolide (2), 12-acetoxy-3-O-acetyl-7-O
      tigloylvilasinin (3) and 12-acetoxy-3-O-acetyl-7-O-methacryloylvilasinin (4),
      along with five known ones, were isolated from seeds of Azadirachta indica A.
      Juss. Their structures were elucidated by various spectroscopic methods,
      including UV, IR, MS, NMR, X-ray crystallography, quantum chemical calculation,
      as well as by comparison of their spectroscopic data with those reported. In the
      in vitro cytotoxic assay, 2 showed inhibitory activity against human breast
      cancer MDA-MB-231 cell line with IC50 value of 7.68+/-1.74 MUmol/L, and 5
      inhibited growth of human cervical cancer Hela cell line, melanoma A375 cell line
      and promyelocytic leukemia HL-60 cell line, with IC50 12.00+/-2.08, 17.44+/-2.11,
      and 13.95+/-5.74 MUmol/L, respectively.

PMID- 30109188
TI  - Authentic compound-free strategy for simultaneous determination of primary
      coumarins in Peucedani Radix using offline high performance liquid chromatography
      nuclear magnetic resonance spectroscopy-tandem mass spectrometry.
AB  - Herein, a strategy is proposed for the simultaneous determination of primary
      coumarins in Peucedani Radix (Chinese name: Qianhu). The methodology consists of
      three consecutive steps: 1) Semi-preparative LC in combination with a home-made
      automated fraction collection module to fragment the universal metabolome
      standard into ten fractions (Frs. I-X); 2) LC-accurate MS/MS and quantitative 1H
      NMR spectroscopy conducted in parallel to acquire the qualitative and
      quantitative data of each fraction; 3) Robust identification and quantification
      of components by use of LC coupled to multiple reaction monitoring. In this final
      step, the most significant fractions (Frs. III-X) were pooled to serve as the
      pseudo-mixed standard solution. Meticulous online parameter optimization was
      performed to obtain the optimal parameters, including ion transitions and
      collision energies. Concerns were particularly paid onto pursuing the parameters
      being capable of monitoring regio-specific isomers, notably praeruptorin E vs. 3'
      isovaleryl-4'-angeloylkhellactone. The quantitative performance of the method was
      validated according to diverse assays. Eleven primary coumarins (1-11) were
      unambiguously identified and absolutely quantified, even though no external
      reference compound was used. Above all, the integrated strategy not only provides
      a feasible pipeline for the quality assessment of Peucedani Radix, but more
      importantly, shows the potential for authentic compound-free quantitative
      evaluation of traditional Chinese medicines.

PMID- 30109189
TI  - In situ monitoring of the structural change of microemulsions in simulated
      gastrointestinal conditions by SAXS and FRET.
AB  - Microemulsions are promising drug delivery systems for the oral administration of
      poorly water-soluble drugs. However, the evolution of microemulsions in the
      gastrointestinal tract is still poorly characterized, especially the structural
      change of microemulsions under the effect of lipase and mucus. To better
      understand the fate of microemulsions in the gastrointestinal tract, we applied
      small-angle X-ray scattering (SAXS) and fluorescence resonance energy transfer
      (FRET) to monitor the structural change of microemulsions under the effect of
      lipolysis and mucus. First, the effect of lipolysis on microemulsions was studied
      by SAXS, which found the generation of liquid crystalline phases. Meanwhile, FRET
      spectra indicated micelles with smaller particle sizes were generated during
      lipolysis, which could be affected by CaCl2, bile salts and lecithin. Then, the
      effect of mucus on the structural change of lipolysed microemulsions was studied.
      The results of SAXS and FRET indicated that the liquid crystalline phases
      disappeared, and more micelles were generated. In summary, we studied the
      structural change of microemulsions in simulated gastrointestinal conditions by
      SAXS and FRET, and successfully monitored the appearance and disappearance of the
      liquid crystalline phases and micelles.

PMID- 30109190
TI  - Genome-wide characterization and analysis of bHLH transcription factors in Panax
      ginseng.
AB  - Ginseng (Panax ginseng C.A. Meyer) is one of the best-selling herbal medicines,
      with ginsenosides as its main pharmacologically active constituents. Although
      extensive chemical and pharmaceutical studies of these compounds have been
      performed, genome-wide studies of the basic helix-loop-helix (bHLH) transcription
      factors of ginseng are still limited. The bHLH transcription factor family is one
      of the largest transcription factor families found in eukaryotic organisms, and
      these proteins are involved in a myriad of regulatory processes. In our study,
      169 bHLH transcription factor genes were identified in the genome of P. ginseng,
      and phylogenetic analysis indicated that these PGbHLHs could be classified into
      24 subfamilies. A total of 21 RNA-seq data sets, including two sequencing
      libraries for jasmonate (JA)-responsive and 19 reported libraries for organ
      specific expression analyses were constructed. Through a combination of gene
      specific expression patterns and chemical contents, 6 PGbHLH genes from 4
      subfamilies were revealed to be potentially involved in the regulation of
      ginsenoside biosynthesis. These 6 PGbHLHs, which had distinct target genes, were
      further divided into two groups depending on the absence of MYC-N structure. Our
      results would provide a foundation for understanding the molecular basis and
      regulatory mechanisms of bHLH transcription factor action in P. ginseng.

PMID- 30109191
TI  - Biocatalytic access to diverse prenylflavonoids by combining a regiospecific C
      prenyltransferase and a stereospecific chalcone isomerase.
AB  - Prenylflavonoids are valuable natural products that have diverse biological
      properties, and are usually generated biologically by multiple metabolic enzymes
      in nature. In this study, structurally diverse prenylflavonoids were conveniently
      synthesized by enzymatic catalysis by combining GuILDT, a regiospecific chalcone
      prenyltransferase, and GuCHI, a stereospecific chalcone isomerase that has
      promiscuous activity for both chalcones and prenylchalcones as substrates. Our
      findings provided a new approach for the synthesis of natural/unnatural bioactive
      prenylflavonoids, including prenylchalcones and optical prenylflavanones with
      chalcone origins.

PMID- 30109192
TI  - Epigenetic modification in histone deacetylase deletion strain of Calcarisporium
      arbuscula leads to diverse diterpenoids.
AB  - Epigenetic modifications have been proved to be a powerful way to activate silent
      gene clusters and lead to diverse secondary metabolites in fungi. Previously,
      inactivation of a histone H3 deacetylase in Calcarisporium arbuscula had led to
      pleiotropic activation and overexpression of more than 75% of the biosynthetic
      genes and isolation of ten compounds. Further investigation of the crude extract
      of C. arbuscula DeltahdaA strain resulted in the isolation of twelve new
      diterpenoids including three cassanes (1-3), one cleistanthane (4), six pimaranes
      (5-10), and two isopimaranes (11 and 12) along with two know cleistanthane
      analogues. Their structures were elucidated by extensive NMR spectroscopic data
      analysis. Compounds 2 and 4 showed potent inhibitory effects on the expression of
      MMP1 and MMP2 (matrix metalloproteinases family) in human breast cancer (MCF-7)
      cells.

PMID- 30109193
TI  - Partial anomalous pulmonary venous return with dual drainage to the superior vena
      cava and left atrium with pulmonary hypertension.
AB  - Partial anomalous pulmonary venous return (PAPVR) is a rare congenital
      cardiovascular anomaly. A 68-year-old woman was referred to our hospital for
      detailed examination for pulmonary hypertension (PH). She had been diagnosed as
      having pulmonary artery dilation and suspected to have PH during a health check
      seven years prior. A contrast computed tomography showed that the right upper
      pulmonary vein (RUPV) returned to the superior vena cava (SVC) with a preserved
      normal connection to the left atrium (LA). Surgical repair was performed. We
      reported an extremely rare case of isolated PAPVR with PH showing dual drainage
      into the SVC and LA.

PMID- 30109194
TI  - Connecting occipital alpha band peak frequency, visual temporal resolution, and
      occipital GABA levels in healthy participants and hepatic encephalopathy
      patients.
AB  - Recent studies have proposed a connection between the individual alpha band peak
      frequency and the temporal resolution of visual perception in healthy human
      participants. This connection rests on animal studies describing oscillations in
      the alpha band as a mode of phasic thalamocortical information transfer for low
      level visual stimuli, which critically relies on GABAergic interneurons. Here, we
      investigated the interplay of these parameters by measuring occipital alpha band
      peak frequency by means of magnetoencephalography, visual temporal resolution by
      means of behavioral testing, and occipital GABA levels by means of magnetic
      resonance spectroscopy. Importantly, we investigated a sample of healthy
      participants and patients with varying grades of hepatic encephalopathy, which
      are known to exhibit decreases in the investigated parameters, thus providing an
      increased parameter space. We found that occipital alpha band peak frequency and
      visual temporal resolution were positively correlated, i.e., higher occipital
      alpha band peak frequencies were on average related to a higher temporal
      resolution. Likewise, occipital alpha band peak frequency correlated positively
      with occipital GABA levels. However, correlations were significant only when both
      healthy participants and patients were included in the analysis, thereby
      indicating a connection of the measures on group level (instead of the individual
      level). These findings provide new insights into neurophysiological and
      neurochemical underpinnings of visual perception.

PMID- 30109197
TI  - Multi-residue pesticides analysis in water samples using reverse phase high
      performance liquid chromatography (RP-HPLC).
AB  - India is one of the leading suppliers of agrochemicals and has the largest
      pesticide industry in Asia. Among various Indian states, Punjab is the primary
      user of pesticides. Presence of pesticide residue in water and food products of
      Punjab is well documented. The present study was designed to envisage the level
      of pesticide contamination in pond water of eleven villages of Amritsar district
      of Punjab, India. A rapid and concurrent method for the identification and
      quantification of pesticides in water samples was developed and validated. The
      method validation parameters exhibited high sensitivity of the developed method
      and the proficiency for the identification and quantification of pesticide
      residues in water samples. The RP-HPLC method described here *is a novel method
      which is applicable for simple, rapid and precise detection of pesticides.*40.02%
      of water samples were found contaminated with multi-residue
      pesticides.*carbofuran was the most abundant pesticide which was present in
      18.18% samples.

PMID- 30109195
TI  - Photoacoustic tomography of intact human prostates and vascular texture analysis
      identify prostate cancer biopsy targets.
AB  - Prostate cancer is poorly visualized on ultrasonography (US) so that current
      biopsy requires either a templated technique or guidance after fusion of US with
      magnetic resonance imaging. Here we determined the ability for photoacoustic
      tomography (PAT) and US followed by texture-based image processing to identify
      prostate biopsy targets. K-means clustering feature learning and testing was
      performed on separate datasets comprised of 1064 and 1197 nm PAT and US images of
      intact, ex vivo human prostates. 1197 nm PAT was found to not contribute to the
      feature learning, and thus, only 1064 nm PAT and US images were used for final
      feature testing. Biopsy targets, determined by the tumor-assigned pixels' center
      of mass, located 100% of the primary lesions and 67% of the secondary lesions. In
      conclusion, 1064 nm PAT and US texture-based feature analysis provided successful
      prostate biopsy targets.

PMID- 30109198
TI  - Method to extract an enhanced cervical vertebrae area from a digital X-ray image.
AB  - Combination of digital X-ray with image processing techniques has the potential
      to extract useful information for healthcare professionals (physicians). From all
      the information that can be extracted from X-ray images, information concerning
      the human cervical vertebrae is relevant for the medical area. Therefore, in this
      work we present a simple enhanced region of interest (ROI) selection tool to
      select automatically the region that contains most of the information concerning
      to cervical vertebrae. The ROI-selection method reduces the size of a lateral or
      frontal digital X-ray by 30-60% without losing significance in the resulting
      image. This is achieved by an adjustment of dimensions in the image while the
      cervical area is preserved. Moreover, the visual quality is improved by
      performing a contrast enhancement in the region of interest. *Automatic threshold
      selection is computationally more efficient than traditional image segmentation
      techniques.*Reduce size in comparison with original image (enhancing
      ROI).*Independence of depth gray scale space.

PMID- 30109199
TI  - An erosion control and soil conservation method for agrarian uses based on
      determining the erosion threshold.
AB  - We present a practical method to control erosion and soil conservation for
      agrarian activity. The method consists of four steps: (1) analyse the erosive
      state (as a percentage of the area affected) and soil losses (in m3 ha-1) by
      means of visual indicators (physical features on the soil surface that have been
      formed by erosion) and analyse environmental factors (as possible erodibility
      factors); (2) determine the factors of erodibility; (3) calculate the erosion
      threshold (value of the erodibility factor beyond which effective control of
      erosion is achieved), by statistical analysis of the databases collected in the
      field; (4) verify this result by applying a qualitative assessment of erosive
      intensity, using visual indicators. The erosion threshold is of particular
      interest for practical purposes because it can be used to improve the planning of
      agricultural activity, from the standpoint of soil conservation, thus promoting
      sustainable land use. This study makes the following main contributions to
      knowledge in this field: *It presents a new method to address erosion control,
      based on determining the erosion threshold.*Appropriate environmental and
      management conditions for effective erosion control are identified.*The method is
      simple to apply, which facilitates its implementation.

PMID- 30109200
TI  - Guidelines for Transcatheter Aortic Valve Replacement in Korea: Past Obstacles
      and Future Perspectives.
AB  - Background: Analyses of the efficacy and safety of transcatheter aortic valve
      replacement (TAVR) in most countries have been based on outcomes obtained in
      accordance with national practice guidelines and monitoring protocols. The
      purpose of this study is to share our experience regarding the process for
      establishing guidelines and monitoring protocols for the use of TAVR in Korea, in
      the hopes that it may be helpful to others undergoing a similar process in their
      own country. Methods: The Korean guidelines for TAVR were established on June 1,
      2015 in through a tri-party agreement involving the Department of Health and
      Welfare, the Korean Society of Thoracic and Cardiovascular Surgery and the Korean
      Society of Cardiology. We agreed to monitor the guidelines transparently and to
      exchange opinions regarding amendments or continuation of its contents after 3
      years of monitoring. Results: The monitoring meetings were not held as regularly
      as agreed, and monitoring was also made difficult by insufficient and incomplete
      data. Nevertheless, during the meetings, measures to improve the monitoring
      process were discussed, and accordingly, an agreement was made to continue the
      monitoring process, with the aim of completing data collection by 2018.
      Conclusion: Compliance with guidelines is critical for assessing the efficacy and
      safety of TAVR. Moreover, the TAVR monitoring process must be properly conducted
      for an accurate evaluation to be made. Any country planning to introduce TAVR may
      encounter difficulties with regards to the optimal initiation strategy and
      subsequent monitoring. Nevertheless, continued efforts should be made to persuade
      the government and the corresponding medical societies to facilitate the optimal
      application of TAVR.

PMID- 30109196
TI  - Retroviral nucleocapsid proteins and DNA strand transfers.
AB  - An infectious retroviral particle contains 1000-1500 molecules of the
      nucleocapsid protein (NC) that cover the diploid RNA genome. NC is a small zinc
      finger protein that possesses nucleic acid chaperone activity that enables NC to
      rearrange DNA and RNA molecules into the most thermodynamically stable structures
      usually those containing the maximum number of base pairs. Thanks to the
      chaperone activity, NC plays an essential role in reverse transcription of the
      retroviral genome by facilitating the strand transfer reactions of this process.
      In addition, these reactions are involved in recombination events that can
      generate multiple drug resistance mutations in the presence of anti-HIV-1 drugs.
      The strand transfer reactions rely on base pairing of folded DNA/RNA structures.
      The molecular mechanisms responsible for NC-mediated strand transfer reactions
      are presented and discussed in this review. Antiretroviral strategies targeting
      the NC-mediated strand transfer events are also discussed.

PMID- 30109201
TI  - Alexander the Great's Life-Threatening Thoracic Trauma.
AB  - Alexander the Great was a world-class leader with tremendous courage. He paid no
      heed to the dangers of the battlefield, so he was always in the front lines.
      However, his excessive courage put his life in danger. Herein, we present an
      analysis of the information contained in the chronicles about a very severe, life
      threatening thoracic trauma that nearly killed the great stratelates. The
      detailed descriptions made by Arrianus allow us to conclude that Alexander the
      Great experienced a nearly fatal case of tension pneumothorax. Information on how
      he was managed is also presented.

PMID- 30109202
TI  - Early Experiences with Ultra-Fast-Track Extubation after Surgery for Congenital
      Heart Disease at a Single Center.
AB  - Background: Early extubation after cardiovascular surgery has some clinical
      advantages, including reduced hospitalization costs. Herein, we review the
      results of ultra-fast-track (UFT) extubation, which refers to extubation
      performed on the operating table just after the operation, or within 1-2 hours
      after surgery, in patients with congenital cardiac disease. Methods: We performed
      UFT extubation in patients (n=72) with a relatively simple congenital cardiac
      defect or who underwent a simple operation starting in September 2016. To
      evaluate the feasibility and effectiveness of our recently introduced UFT
      extubation strategy, we retrospectively reviewed 195 patients who underwent
      similar operations for similar diseases from September 2015 to September 2017,
      including the 1-year periods immediately before and after the introduction of the
      UFT extubation protocol. Propensity scores were used to assess the effects of UFT
      extubation on length of stay (LOS) in the intensive care unit (ICU), hospital
      LOS, and medical costs. Results: After propensity-score matching using logistic
      regression analysis, 47 patients were matched in each group. The mean ICU LOS
      (16.3+/-28.6 [UFT] vs. 28.0+/-16.8 [non-UFT] hours, p=0.018) was significantly
      shorter in the UFT group. The total medical costs (182.6+/-3.5 [UFT] vs. 187.1+/
      55.6 [non-UFT] *100,000 Korean won [KRW], p=0.639) and hospital stay expenses
      (48.3+/-13.6 [UFT] vs. 54.8+/-29.0 [non-UFT] *100,000 KRW, p=0.164) did not
      significantly differ between the groups. Conclusion: UFT extubation decreased the
      ICU LOS and mechanical ventilation time, but was not associated with
      postoperative hospital LOS or medical expenses in patients with simple congenital
      cardiac disease.

PMID- 30109203
TI  - Thoracic Scoliosis in Patients with Primary Spontaneous Pneumothorax.
AB  - Background: Primary spontaneous pneumothorax (PSP) affects patients without
      clinically apparent lung disorder found in tall and thin young male. Scoliosis
      refers to curves exceeding 10 degrees  Cobb angle observed through chest X-ray
      and affects 2% to 4% of adolescents. Both conditions are commonly encountered in
      primary health care setting. The aim of this study is to access the correlation
      of thoracic scoliosis and PSP in adolescent. Methods: A retrospective analysis
      was conducted for patients diagnosed for PSP in Konyang University Hospital
      between January 2010 and March 2017. Chest X-rays of 222 patients and 155 normal
      control (NC) cases were reviewed to measure the Cobb angle. Greater than 10
      degrees  of Cobb angle is diagnosed as scoliosis. Results: Scoliosis in patient
      with PSP has higher incidence than that of NC group (p<0.001). Median value of
      Cobb angle is 12.9 degrees  in PSP group and 14.7 degrees  in NC group.
      Directional relationship between scoliosis and pneumothorax in PSP group is also
      observed; 40.5% cases are ipsilateral and 59.5% are contralateral. Conclusion:
      PSP patients tend to have thoracic scoliosis more commonly compared with normal
      healthy adolescent. Scoliosis may contribute to heterogeneity of alveolar
      pressure which exacerbates subpleural bleb formation that can cause pneumothorax.
      The causal relationship is unclear and further studies are needed in the future.

PMID- 30109204
TI  - Feasibility and Safety of a New Chest Drain Wound Closure Method with Knotless
      Sutures.
AB  - Background: A method of wound closure using knotless suture material in the chest
      tube site has been introduced at our center, and is now widely used as the
      primary method of closing chest tube wounds in video- assisted thoracic surgery
      (VATS) because it provides cosmetic benefits and causes less pain. Methods: We
      included 109 patients who underwent VATS pulmonary resection at Samsung Medical
      Center from October 1 to October 31, 2016. Eighty-five patients underwent VATS
      pulmonary resection with chest drain wound closure utilizing knotless suture
      material, and 24 patients underwent VATS pulmonary resection with chest drain
      wound closure by the conventional method. Complications related to the chest
      drain wound were compared between the 2 groups. Results: There were 2 cases of
      pneumothorax after chest tube removal in both groups (8.3% in the conventional
      group, 2.3% in the knotless suture group; p=0.172) and there was 1 case of wound
      discharge due to wound dehiscence in the knotless suture group (0% in the
      conventional group, 1.2% in the knotless suture group; p=0.453). There was no
      reported case of chest tube dislodgement in either group. The complication rates
      were non-significantly different between the 2 groups. Conclusion: The results
      for the complication rates of this new chest drain wound closure method suggest
      that this method is not inferior to the conventional method. Chest drain wound
      closure using knotless suture material is feasible based on the short-term
      results of the complication rate.

PMID- 30109205
TI  - Comparison of Radiofrequency Ablation and Cryoablation for the Recovery of Atrial
      Contractility and Survival.
AB  - Background: Limited comparative data are available on the efficacy of
      cryoablation versus radiofrequency ablation in patients with atrial fibrillation.
      This study aimed to compare radiofrequency ablation and cryoablation with regard
      to clinical outcomes and the restoration of sinus rhythm or atrial contractility.
      Methods: A total of 239 patients who underwent surgical ablation between August
      2003 and December 2016 at our institution were included. The patients were
      divided into 2 groups according to the energy device that was used (group A:
      n=140, radiofrequency ablator; group B: n=99, cryoablator). Echocardiographic
      data, overall survival, and major cardiovascular and cerebrovascular event
      (MACCE)-free survival were compared between the 2 groups. Results: At 1 year of
      follow-up, the atrial contractility recovery rate was 32.2% (19 of 59) in group A
      and 48.8% (21 of 44) in group B. In addition, cryoablation was found to be a
      predictive factor for the recovery of atrial contractility (cryoablation vs.
      radiofrequency ablation: odds ratio, 2.540; 95% confidence interval, 1.063-6.071;
      p=0.036). The left ventricular ejection fraction was significantly higher in
      group B (53.1%+/-11.5% vs. 59.1%+/-6.3%, p=0.001). The median follow-up duration
      was 36 months. The 5-year overall survival rate was 80.1%+/-3.6% in group A and
      92.1%+/-2.9% in group B (p=0.400). The 5-year MACCE-free survival rate was
      70.3%+/-4.0% in group A and 70.9%+/-5.6% in group B (p=0.818). Conclusion:
      Cryoablation was associated with a higher atrial contractility restoration rate
      and better left ventricular function than radiofrequency ablation. However, no
      significant relationship was observed between the energy source and overall or
      MACCE-free survival.

PMID- 30109206
TI  - Treatment of Fungal Empyema Combined with Osteoradionecrosis by Thoracoplasty and
      Myocutaneous Flap Transposition.
AB  - We report the rare case of a 58-year-old woman who was diagnosed with fungal
      empyema thoracis combined with osteoradionecrosis. After 32 months of home care
      followed by open window thoracostomy, thoracoplasty with serratus anterior muscle
      transposition and a latissimus dorsi myocutaneous flap was performed
      successfully. Although thoracoplasty is now rarely indicated, it is still the
      treatment of choice for the complete obliteration of thoracic spaces.

PMID- 30109207
TI  - Iatrogenic Tracheal Posterior Wall Perforation Repaired with Bronchoscope-Guided
      Knotless Sutures Through Tracheostomy.
AB  - A 68-year-old man presented with a posterior tracheal wall injury caused by
      percutaneous dilatational tracheostomy. The wound was immediately covered with an
      absorbable polyglycolic acid sheet. Ten days after the injury, the perforation
      was closed with knotless sutures using a Castroviejo needle-holder through the
      tracheostomy. The successful repair in this case indicates the feasibility of the
      knotless suture technique for perforations. The technique is described in detail
      in this report. The patient was weaned from the mechanical ventilator on
      postoperative day 25. In cases of posterior tracheal posterior wall perforation,
      every effort should be made to repair the perforation through an existing
      opening.

PMID- 30109208
TI  - Isolated Unilateral Absence of Pulmonary Artery Associated with Contralateral
      Lung Cancer.
AB  - Unilateral absence of a pulmonary artery (UAPA) is a rare congenital anomaly that
      may present with various symptoms, depending on the nature and severity of other
      cardiovascular anomalies. Furthermore, contralateral lung surgery in patients
      with UAPA is extremely rare, and clinical experience is limited. This report
      describes a case of surgical treatment of contralateral primary lung cancer in a
      patient with isolated UAPA. A 56-year-old man was diagnosed with primary lung
      cancer accompanied by isolated UAPA on the contralateral side. He underwent
      meticulous cardiorespiratory function tests preoperatively. We performed a right
      lower lobectomy. Although in the immediate postoperative period, the patient
      suffered from a mild decline in his respiratory function, he recovered
      uneventfully. The present case shows that preoperative awareness of UAPA and
      meticulous perioperative management enable contralateral lung surgery to be
      performed safely.

PMID- 30109209
TI  - Minimally Invasive Redo Mitral Valve Replacement under Fibrillatory Arrest in a
      Patient with a Calcified Aorta and Patent Previous Bypass Grafts.
AB  - A 73-year-old woman who underwent combined bioprosthetic mitral valve
      replacement, tricuspid ring annuloplasty, and coronary artery bypass grafting 12
      years previously visited our clinic due to aggravated dyspnea caused by
      structural valve deterioration of the mitral prosthesis. Because aortic or
      femoral artery cannulation and cross-clamping would have a high risk of stroke
      owing to severe calcification of the ascending aorta and ilio-femoral vessels,
      and because there was a risk of redo sternotomy due to the patent bypass grafts,
      a comprehensive approach including axillary artery cannulation, a minimally
      invasive right thoracotomy approach, and a clampless hypothermic fibrillatory
      arrest technique was used during redo mitral valve replacement.

PMID- 30109210
TI  - Favorable Aortic Remodeling Following Serial False Lumen Procedures in a Case of
      Chronic Type IIIb Dissection.
AB  - We report a case of acute type I aortic dissection in which an emergency graft
      replacement of the ascending aorta and innominate artery was performed. We
      performed false lumen thrombosis through hybrid thoracic endovascular aortic
      repair to seal the primary entry tear, followed by false lumen obliteration at
      the level of the descending thoracic aorta, abdominal aorta, and right common
      iliac artery. Over a period of 4.5 years, we used Amplatzer vascular plugs and
      coils based on our computed tomography angiography follow-up protocol.

PMID- 30109211
TI  - Lobectomy due to Pulmonary Vein Occlusion after Radiofrequency Ablation for
      Atrial Fibrillation.
AB  - Radiofrequency ablation is an effective treatment for atrial fibrillation.
      Pulmonary vein stenosis/occlusion is one of its rare complications. Herein, the
      case of a 50-year-old man with hemoptysis and migratory pulmonary infiltrations
      after transcatheter radiofrequency ablation for atrial fibrillation is presented.
      Initially, pneumonia, interstitial pulmonary disease, or lung cancer was
      suspected, but wedge resection revealed hemorrhagic infiltrations. Chest computed
      tomography pulmonary angiography detected no left superior pulmonary vein due to
      its total occlusion, and left upper lobectomy was performed. Post-ablation
      pulmonary vein occlusion must be strongly suspected in cases of migratory
      pulmonary infiltrations and/or hemoptysis.

PMID- 30109212
TI  - Editorial: Targeting Phosphorylation and Glycosylation of Membrane-Bound
      Oncogenic Drivers, Receptors and Adhesion Molecules to Control Constitutive
      Proliferation of Human Carcinoma Cells.

PMID- 30109214
TI  - Nucleotide Excision Repair Factor XPC Ameliorates Prognosis by Increasing the
      Susceptibility of Human Colorectal Cancer to Chemotherapy and Ionizing Radiation.
AB  - Nucleotide excision repair (NER) is a DNA damage repair mechanism in mammals, but
      the relationship between NER and human colorectal cancer (HRC) progression has
      not been clarified yet. In this study, the expression of the NER genes XPA, XPC,
      XPF, XPG, ERCC1, and XPD was measured in normal and cancerous human colorectal
      tissue. Among them, only the XPC gene expression was significantly increased in
      colorectal cancer tissue. To establish the role of XPC in colorectal cancer,
      small interference RNA (siRNA) targeting XPC was used to knockdown the expression
      of XPC in HRC cell lines. In addition, an expression vector plasmid containing
      the XPC cDNA was constructed and stably transfected into HRC cell lines to
      overexpress the XPC gene. Interestingly, MTT and apoptosis assay demonstrated
      that XPC gene overexpression significantly increased the susceptibility of HRC
      cell lines to cisplatin and X-ray radiation. In order to study the relationship
      between XPC expression and the progression of HRC, XPC expression was measured in
      167 patients with colorectal cancer. The results showed that patients with high
      XPC expression had longer survival time. Cox regression analysis showed that high
      XPC expression might be a potential predictive factor for colorectal cancer. In
      conclusion, XPC plays a key role in the susceptibility of colorectal cancer to
      chemotherapy and ionizing radiation and is associated with a good patients'
      prognosis.

PMID- 30109215
TI  - Evaluation of Radiomics to Predict the Accuracy of Markerless Motion Tracking of
      Lung Tumors: A Preliminary Study.
AB  - Template-based matching algorithms are currently being considered for markerless
      motion tracking of lung tumors. These algorithms use tumor templates derived from
      the planning CT scan, and track the motion of the tumor on single energy
      fluoroscopic images obtained at the time of treatment. In cases where bone may
      obstruct the view of the tumor, dual energy fluoroscopy may be used to enhance
      soft tissue contrast. The goal of this study is to predict which tumors will have
      a high degree of accuracy for markerless motion tracking based on radiomic
      features obtained from the planning CT scan, using peak-to-sidelobe ratio (PSR)
      as a surrogate of tracking accuracy. In this study, CT imaging data of 8 lung
      cancer patients were obtained and analyzed through the open source IBEX program
      to generate 2,287 radiomic features. Agglomerative hierarchical clustering was
      used to narrow down these features into 145 clusters comprised of the highest
      correlation to PSR. The features among the clusters with the least inter
      correlation were then chosen to limit redundancy in the data. The results of this
      study demonstrated a number of radiomic features that are positively correlated
      to PSR. The features with the highest degree of correlation included complexity,
      orientation and range. This approach may be used to determine patients for whom
      markerless motion tracking would be beneficial.

PMID- 30109216
TI  - Phylogenetic Lineages of Francisella tularensis in Animals.
AB  - Tularemia is a zoonotic disease caused by the facultative intracellular bacterium
      Francisella tularensis. This microorganism can infect a plethora of animal
      species and its ecology is particularly complex. Much research was performed to
      understand its biology but many questions are still open, especially concerning
      the life cycle of this bacterium in the environment related to physical and
      biological parameters. Numerous animals are major hosts of F. tularensis but
      precise reservoir species are not yet well defined. Moreover, the exact range of
      species susceptible to tularemia is not clear and is complicated by the
      differences in virulence and ecology observed among the subspecies of F.
      tularensis. Indeed, different life cycles in nature, including the animal species
      concerned, were previously described for F. tularensis subsp. tularensis and F.
      tularensis subsp. holarctica. Recently, molecular techniques showing adequate
      discrimination between strains were developed, leading to the possibility to
      investigate links between phylogenetic lineages and infection in animals. New
      perspectives in research are now possible thanks to the information available and
      the simplicity of the molecular procedures. Current studies are unfolding the
      evolution of F. tularensis and these developments will lead to the elucidation of
      geographical and ecological differences observed by veterinarians,
      microbiologists and conservation biologists. However, systematic, coordinated
      collection of data and extensive sampling are important to efficiently assemble
      the findings of future research.

PMID- 30109219
TI  - Editorial: Pediatric Hypertension: Update.

PMID- 30109218
TI  - Cellular Events of Multinucleated Giant Cells Formation During the Encystation of
      Entamoeba invadens.
AB  - Entamoeba histolytica, the causative agent of amoebiasis, does not form cysts in
      vitro, so reptilian pathogen Entamoeba invadens is used as an Entamoeba
      encystation model. During the in vitro encystation of E. invadens, a few
      multinucleated giant cells (MGC) were also appeared in the culture along with
      cysts. Like the cyst, these MGC's were also formed in the multicellular
      aggregates found in the encystation culture. Time-lapse live cell imaging
      revealed that MGC's were the result of repeated cellular fusion with fusion
      competent trophozoites as a starting point. The early MGC were non-adherent, and
      they moved slowly and randomly in the media, but under confinement, MGC became
      highly motile and directionally persistent. The increased motility resulted in
      rapid cytoplasmic fissions, which indicated the possibility of continuous cell
      fusion and division taking place inside the compact multicellular aggregates.
      Following cell fusion, each nucleus obtained from the fusion-competent
      trophozoites gave rise to four nuclei with half genomic content. All the haploid
      nuclei in MGC later aggregated and fused to form a polyploid nucleus. These
      observations have important implications on Entamoeba biology as they point
      toward the possibility of E. invadens undergoing sexual or parasexual
      reproduction.

PMID- 30109217
TI  - Type VI Secretion Systems Present New Insights on Pathogenic Yersinia.
AB  - The type VI secretion system (T6SS) is a versatile secretion system widely
      distributed in Gram-negative bacteria that delivers multiple effector proteins
      into either prokaryotic or eukaryotic cells, or into the extracellular milieu.
      T6SS participates in various physiological processes including bacterial
      competition, host infection, and stress response. Three pathogenic Yersinia
      species, namely Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia
      enterocolitica, possess different copies of T6SSs with distinct biological
      functions. This review summarizes the pathogenic, antibacterial, and stress
      resistant roles of T6SS in Yersinia and the ion-transporting ability in Y.
      pseudotuberculosis. In addition, the T6SS-related effectors and regulators
      identified in Yersinia are discussed.

PMID- 30109213
TI  - "Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway.
AB  - Janus tyrosine kinase (JAK) family of proteins have been identified as crucial
      proteins in signal transduction initiated by a wide range of membrane receptors.
      Among the proteins in this family JAK2 has been associated with important
      downstream proteins, including signal transducers and activators of transcription
      (STATs), which in turn regulate the expression of a variety of proteins involved
      in induction or prevention of apoptosis. Therefore, the JAK/STAT signaling axis
      plays a major role in the proliferation and survival of different cancer cells,
      and may even be involved in resistance mechanisms against molecularly targeted
      drugs. Despite extensive research focused on the protein structure and mechanisms
      of activation of JAKs, and signal transduction through these proteins, their
      importance in cancer initiation and progression seem to be underestimated. This
      manuscript is an attempt to highlight the role of JAK proteins in cancer biology,
      the most recent developments in targeting JAKs, and the central role they play in
      intracellular cross-talks with other signaling cascades.

PMID- 30109220
TI  - Carbonic Anhydrase II Deficiency: A Rare Case of Severe Obstructive Sleep Apnea.
AB  - The term osteopetrosis describes a group of rare hereditary diseases of the
      skeleton, characterized by an increase in bone density, caused by a defect in the
      development or function of osteoclasts. It comprises a clinically and genetically
      heterogeneous conditions ranging from infantile onset life-threatening forms to
      mildest adult onset forms. "Malignant" osteopetrosis is characterized by bone
      fragility, short stature, compressive neuropathies, hypocalcaemia, pancytopaenia.
      The deficiency of carbonic anhydrase II causes a moderate form, presenting
      classically as a triad of osteopetrosis, renal tubular acidosis (RTA), and
      cerebral calcification. This condition leads to specific craniofacial
      dysmorphisms associated with upper airway obstruction that may result in
      obstructive sleep apnea. Herein we report a case of osteopetrosis with RTA
      associated with severe OSAS successfully treated with continuous positive airway
      pressure (CPAP).

PMID- 30109221
TI  - The Influence of Diet on Fertility and the Implications for Public Health
      Nutrition in the United States.
AB  - Despite growing evidence of the impact of diet on human fertility, few studies
      have examined the public health implications of this association in the United
      States (U.S.). This narrative review summarizes current scientific evidence on
      associations between dietary intake and fertility, discusses challenges in the
      public health landscape surrounding infertility, and proposes evidence-based
      recommendations to address these issues. Diets high in unsaturated fats, whole
      grains, vegetables, and fish have been associated with improved fertility in both
      women and men. While current evidence on the role of dairy, alcohol, and caffeine
      is inconsistent, saturated fats, and sugar have been associated with poorer
      fertility outcomes in women and men. Furthermore, women and men with obesity
      [body mass index (BMI) >= 30 kg/m2] have a higher risk of infertility. This risk
      is extended to women who are underweight (BMI <20 kg/m2). Diet and BMI influence
      outcomes during clinical treatment for infertility. Further, women in the U.S.
      who belong to an underrepresented minority group, have low income, or have low
      educational attainment, have significantly higher rates of infertility outcomes
      as compared to women who are non-Hispanic white, have high income, or have high
      educational attainment. Given this, it may be prudent to integrate nutrition
      counseling into both clinical guidelines for infertility as well as national
      dietary guidelines for individuals of reproductive age. Further studies on diet
      and reproductive health may enhance our ability to improve existing fertility
      programs across the U.S. and to deliver tailored care to women and men within at
      risk groups.

PMID- 30109222
TI  - Behind Closed Doors: The Priorities of the Alcohol Industry as Communicated in a
      Trade Magazine.
AB  - Background: Efforts to reduce alcohol-related harm face strong resistance from
      the alcohol industry. It is important to monitor industry actions over time to
      assist in developing appropriate responses to this resistance. Monitoring can
      enable public health to identify industry positions on alcohol policy issues,
      stay abreast of current and emerging marketing tactics, and inform the
      development of possible counter-actions. One form of monitoring is the
      examination of industry trade publications where the industry converses with
      itself. The aim of this study was to assess industry strategic approaches as
      communicated in articles published in a leading Australian alcohol trade magazine
      to provide insights for policy makers and advocacy groups. Methods: Thematic
      analysis of 362 articles published in a trade magazine over a one-year period.
      Results: Three primary themes were evident in the articles: (1) the
      legitimization of alcohol as an important social and economic product, (2) the
      portrayal of the industry as trustworthy and benign, and (3) the strategic
      embedding of alcohol in various facets of everyday life. Conclusions: There was a
      general failure to acknowledge the substantial burden of disease caused by
      alcohol products, and instead much effort was expended on legitimizing the
      product and the companies responsible for its production, distribution, and
      promotion. The level of denial exhibited shows that additional regulation of the
      industry and its tactics will need to proceed without industry acceptance. Clear
      resistance to increasing consumer protections also points to the futility of
      inviting industry members to the policy table.

PMID- 30109223
TI  - Two New Fluorinated Phenol Derivatives Pyridine Schiff Bases: Synthesis,
      Spectral, Theoretical Characterization, Inclusion in Epichlorohydrin-beta
      Cyclodextrin Polymer, and Antifungal Effect.
AB  - It has been reported that the structure of the Schiff bases is fundamental for
      their function in biomedical applications. Pyridine Schiff bases are
      characterized by the presence of a pyridine and a phenolic ring, connected by an
      azomethine group. In this case, the nitrogen present in the pyridine is
      responsible for antifungal effects, where the phenolic ring may be also
      participating in this bioactivity. In this study, we synthesized two new pyridine
      Schiff Bases: (E)-2-[(3-Amino-pyridin-4-ylimino)-methyl]-4,6-difluoro-phenol (F1)
      and (E)- 2-[(3-Amino-pyridin-4-ylimino)-methyl]-6-fluoro-phenol (F2), which only
      differ in the fluorine substitutions in the phenolic ring. We fully characterized
      both F1 and F2 by FTIR, UV-vis, 1H; 13C; 19F-NMR, DEPT, HHCOSY, TOCSY, and cyclic
      voltammetry, as well as by computational studies (DFT), and NBO analysis. In
      addition, we assessed the antifungal activity of both F1 (two fluorine
      substitution at positions 4 and 6 in the phenolic ring) and F2 (one fluorine
      substitution at position 6 in the phenolic ring) against yeasts. We found that
      only F1 exerted a clear antifungal activity, showing that, for these kind of
      Schiff bases, the phenolic ring substitutions can modulate biological properties.
      In addition, we included F1 and F2 into in epichlorohydrin-beta-cyclodextrin
      polymer (betaCD), where the Schiff bases remained inside the betaCD as determined
      by the ki , TGA, DSC, and SBET. We found that the inclusion in betaCD improved
      the solubility in aqueous media and the antifungal activity of both F1 and F2,
      revealing antimicrobial effects normally hidden by the presence of common
      solvents (e.g., DMSO) with some cellular inhibitory activity. The study of
      structural prerequisites for antimicrobial activity, and the inclusion in
      polymers to improve solubility, is important for the design of new drugs.

PMID- 30109224
TI  - Water-Soluble and Insoluble Polymers, Nanoparticles, Nanocomposites and Hybrids
      With Ability to Remove Hazardous Inorganic Pollutants in Water.
AB  - The polymeric materials have presented a great development in adsorption
      processes for the treatment of polluted waters. The aim of the current review is
      to present the recent developments in this field of study by examining research
      of systems like functional water-soluble polymers and water-soluble polymer-metal
      complexes coupled to ultrafiltration membranes for decontamination processes in
      liquid-liquid phase. Noticing that a water-soluble polymer can be turned into
      insoluble compounds by setting a crosslinking point, connecting the polymer
      chains leading to polymer resins suitable for solid-liquid extraction processes.
      Moreover, these crosslinked polymers can be used to develop more complex systems
      such as (nano)composite and hybrid adsorbents, combining the polymers with
      inorganic moieties such as metal oxides. This combination results in novel
      materials that overcome some drawbacks of each separated components and enhance
      the sorption performance. In addition, new trends in hybrid methods combining of
      water-soluble polymers, membranes, and electrocatalysis/photocatalysis to remove
      inorganic pollutants have been discussed in this review.

PMID- 30109225
TI  - Luminescent Polynuclear Zn- and Cd-Ln Square-Like Nanoclusters With a Flexible
      Long-Chain Schiff Base Ligand.
AB  - Two series of Zn-Ln and Cd-Ln nanoclusters [Ln4Zn8L2(OAc)20(OH)4] [Ln = Nd (1),
      Yb (2), and Sm (3)] and [Ln2Cd2L2(OAc)2(OH)2(OCH3)2] [Ln = Nd (4), Yb (5), and Sm
      (6)] were prepared using a long-chain Schiff base ligand with a flexible
      (CH2)2O(CH2)2O(CH2)2 chain. All these clusters show square-like structures. The
      Schiff base ligands show "linear" configurations in the structures of 1-6, and
      the metric dimensions of Zn-Ln and Cd-Ln clusters measure ~8 * 14 * 21 and 8 * 12
      * 12 A, respectively. The study of luminescence properties shows that the Zn/L
      and Cd/L chromophores can effectively transfer energy to the lanthanide ions, and
      1-6 show visible and NIR emissions.

PMID- 30109226
TI  - Spectroscopic Studies as a Toolbox for Biophysical and Chemical Characterization
      of Lipid-Based Nanotherapeutics.
AB  - The goal of this study is to provide tools to minimize trial-and-error in the
      development of novel lipid-based nanotherapeutics, in favor of a rational design
      process. For this purpose, we present case-study examples of biophysical assays
      that help addressing issues of lipid-based nanotherapeutics' profiling and assist
      in the design of lipid nanocarriers for therapeutic usage. The assays presented
      are rooted in spectroscopic methods (steady-state and time-resolved fluorescence;
      UV-Vis derivative spectroscopy; fluorescence anisotropy and fluorescence lifetime
      image microscopy) and allow accessing physical-chemical interactions between
      drugs and lipid nanocarriers, as well as studying interactions between lipid
      based nanotherapeutics and membranes and/or proteins, as this is a key factor in
      predicting their therapeutic and off target effects. Derivative spectroscopy
      revealed Naproxen's high distribution (LogD ~ 3) in different lipid-based
      nanocarriers (micelles and unilamellar or multilamellar vesicles) confirming the
      adequacy of such systems for encapsulating this anti-inflammatory drug.
      Fluorescence quenching studies revealed that the anti-inflammatory drugs
      Acemetacin and Indomethacin can reach an inner location at the lipid nanocarrier
      while being anchored with its carboxylic moiety at the polar headgroup. The least
      observed quenching effect suggested that Tolmetin is probably located at the
      polar headgroup region of the lipid nanocarriers and this superficial location
      may translate in a fast drug release from the nanocarriers. Fluorescent
      anisotropy measurements indicated that the drugs deeply buried within the lipid
      nanocarrier where the ones that had a greater fluidizing effect which can also
      translate in a faster drug release. The drug binding strength to serum albumin
      was also compared for a free drug (Clonixin) or for the same drug after
      encapsulation in a lipid nanocarrier DSPC:DODAP (2:1). Under both conditions
      there is a strong binding to serum albumin, at one binding site, suggesting the
      need to produce a stealth nanosystem. Finally the cellular uptake of lipid
      nanocarriers loaded with Daunorubicin was investigated in cancer cells using
      fluorescence lifetime imaging microscopy. From the images obtained it was
      possible to conclude that even at short incubation times (15 min) there was a
      distribution of the drug in the cytoplasm, whereas for longer incubation periods
      (4 h) the drug has reached the nucleus.

PMID- 30109227
TI  - Real-Time Analysis of Potassium in Infant Formula Powder by Data-Driven Laser
      Induced Breakdown Spectroscopy.
AB  - Potassium represents one of the most crucial minerals in infant formula that
      supports healthy growth and development of infants. Here, a novel strategy for
      the real-time quantification of potassium in infant formula samples is
      introduced. Using laser-induced breakdown spectroscopy (LIBS) in a data-driven
      approach, a modified random frog algorithm (MRFA) is adopted in a higher-density
      discrete wavelet transform (HDWT) domain for the selection of the most important
      features related to potassium, which is named as DD-LIBS. In DD-LIBS, the HDWT
      oversamples the LIBS signals in both time and frequency domains by a factor of
      two, enhancing the spectral expandability in an approximately shift-invariant
      way. The MRFA is thus capable of isolating the features of potassium with
      experience accumulated from the collected LIBS data. Such pretreatment combined
      with a partial least squared (PLS) model can significantly suppress the
      uncontrolled shift and broadening effects on multivariate calibration, improving
      the capability of LIBS for accurate quantification of potassium. The present work
      demonstrates the feasibility of DD-LIBS for the quantification of potassium
      content of 90 commercial infant formula samples. A satisfactory result
      illustrates DD-LIBS as a feasible tool for real-time analysis of potassium
      content with little sample preparation. This strategy may be well extended to
      other element detection in the presence of uncontrolled interference.

PMID- 30109229
TI  - Bioethanol Production From Hydrolyzed Lignocellulosic After Detoxification Via
      Adsorption With Activated Carbon and Dried Air Stripping.
AB  - Bioethanol production has been presented as an alternative for supplying energy
      demand and minimizing greenhouse gases effects. However, due to abrasively
      conditions employed on the biomass during pretreatment and hydrolysis processes,
      inhibitors for fermentation phase such as acetic acid and others can be
      generated. Based on this problem, the aim of this work was to evaluate the
      adsorption of acetic acid on microporous activated carbon and investigate the
      stripping of the same component with dried air. For adsorption process, three
      concentrations of acetic acid (5, 10, and 20%) were analyzed by adsorption
      kinetics and adsorption isotherms (Langmuir and Freundlich models). Pseudo-second
      order model showed to fit better when compared to Pseudo-first order model. The
      Intraparticle Diffusion model presented the first phase of the adsorption as the
      regulating step of the adsorption process. The Langmuir model showed the best
      fitting, and the maximum capacity of adsorption was found as 128.66 mg.g-1. For
      stripping procedure an apparatus was set in order to insert dried air by a
      diffusor within the solution in study. Increasing temperature showed to be
      determinant on augmenting acetic acid evaporation in 2.14 and 6.22 times for 40
      and 60 degrees C when comparing it to 20 degrees C. The application of the
      pickling process for removal of fermentation inhibitors in sugarcane bagasse
      hydrolyzed allowed the production 8.3 g.L-1 of ethanol.

PMID- 30109230
TI  - Potential Roles of the Retinoblastoma Protein in Regulating Genome Editing.
AB  - Genome editing is an important tool for modifying genomic DNA through introducing
      DNA insertion or deletion at specific locations of a genome. Recently CRISPR/Cas9
      has been widely employed to improve the efficiency of genome editing. The Cas9
      nuclease creates site-specific double strand breaks (DSBs) at targeted loci in
      the genome. Subsequently, the DSBs are repaired by two pathways: Homologous
      Recombination (HR) and Non-Homologous End-Joining (NHEJ). HR has been considered
      as "error-free" because it repairs DSBs by copying DNA sequences from a
      homologous DNA template, while NHEJ is "error-prone" as there are base deletions
      or insertions at the breakage site. Recently, RB1, a gene that is commonly
      mutated in retinoblastoma, has been reported to affect the repair efficiencies of
      HR and NHEJ. This review focuses on the roles of RB1 in repairing DNA DSBs, which
      have impacts on the precision and consequences of the genome editing, both at the
      targeted loci and the overall genome.

PMID- 30109231
TI  - Healthy Singleton Pregnancies From Restorative Reproductive Medicine (RRM) After
      Failed IVF.
AB  - Objectives: To determine the live birth rate for patients who chose to undergo
      treatment with Restorative Reproductive Medicine (RRM) after previous IVF
      (includes ICSI). To look at birth outcomes with RRM after IVF, particularly rates
      of twin and higher order pregnancies, premature birth, low birth weight, and
      potential cost savings achieved with RRM. Setting: Two outpatient clinics in
      Ireland providing advanced RRM treatment of infertility. Materials and methods:
      All patients presenting between January 2004 and January 2010, with a history of
      infertility and previous IVF treatment were included if they proceeded beyond the
      initial consultation and began treatment. Main outcome is live birth per couple
      calculated using life table analysis. Results: 403 patients met the study
      criteria, among which 74 had a subsequent live birth. These women had significant
      negative predictive characteristics for healthy live birth including: advanced
      reproductive age (average 37.2 years), an average of 5.8 years of infertility
      with 2.1 (range 1-9) previous IVF attempts, with only 5% having previously had a
      live birth from IVF. Despite these undesirable prognostic indicators, the overall
      RRM live birth rate was 32.1% (crude 18.4%). Women aged 35-38 had a live birth
      rate of 37.5% (crude 23.6%) and older women over 40 had a live birth rate of
      27.4% (crude 16.0%). The average birth weight was 3374g (7lb 7oz) with 92% being
      born at 37+ weeks and no very low birth weight babies. There was only one twin
      pregnancy in the study population; the potential health care savings for
      avoidable multiple pregnancies in these patients was estimated at L205 672
      (USD$284 915). Conclusions: Patients who have already tried IVF can achieve
      comparable live birth outcomes with RRM compared to another cycle of IVF. RRM has
      a low risk of twin or multiple births, and very good neonatal outcomes with a
      potential cost savings to the health care system.

PMID- 30109233
TI  - Trends in Microalgae Incorporation Into Innovative Food Products With Potential
      Health Benefits.
AB  - Microalgae have demonstrated potential to meet the population's need for a more
      sustainable food supply, specifically with respect to protein demand. These
      promising protein sources present several advantages over other currently used
      raw materials from an environmental point of view. Additionally, one of the main
      characteristics of microalgae is the production of bioactive compounds with
      potential benefits for human health. Microalgae exploitation as a source of
      protein (bulk protein) and other valuable products within the food industry still
      presents some drawbacks, mainly because of the underdeveloped technologies and
      processes currently available for microalgae processing. The systematic
      improvement of the technology readiness level (TRL) could help change the current
      situation if applied to microalgae cultivation and processing. High maturity in
      microalgae cultivation and processing technologies also requires improvement of
      the economy of scale and investment of resources in new facilities and research.
      Antioxidative, antihypertensive, immunomodulatory, anticancerogenic, hepato
      protective, and anticoagulant activities have been attributed to some microalgae
      derived compounds such as peptides. Nevertheless, research on this topic is
      scarce and the evidence on potential health benefits is not strong. In the last
      years, the possibility of using microalgae-derived compounds for innovative
      functional food products has become of great interest, but the literature
      available mainly focuses more on the addition of the whole cells or some compound
      already available on the market. This review describes the status of utilising
      microalgae as an ingredient in innovative food products with potential health
      benefits.

PMID- 30109228
TI  - Tissue Engineering and Cell-Based Therapies for Fractures and Bone Defects.
AB  - Bone fractures and segmental bone defects are a significant source of patient
      morbidity and place a staggering economic burden on the healthcare system. The
      annual cost of treating bone defects in the US has been estimated to be $5
      billion, while enormous costs are spent on bone grafts for bone injuries, tumors,
      and other pathologies associated with defective fracture healing. Autologous bone
      grafts represent the gold standard for the treatment of bone defects. However,
      they are associated with variable clinical outcomes, postsurgical morbidity,
      especially at the donor site, and increased surgical costs. In an effort to
      circumvent these limitations, tissue engineering and cell-based therapies have
      been proposed as alternatives to induce and promote bone repair. This review
      focuses on the recent advances in bone tissue engineering (BTE), specifically
      looking at its role in treating delayed fracture healing (non-unions) and the
      resulting segmental bone defects. Herein we discuss: (1) the processes of
      endochondral and intramembranous bone formation; (2) the role of stem cells,
      looking specifically at mesenchymal (MSC), embryonic (ESC), and induced
      pluripotent (iPSC) stem cells as viable building blocks to engineer bone
      implants; (3) the biomaterials used to direct tissue growth, with a focus on
      ceramic, biodegradable polymers, and composite materials; (4) the growth factors
      and molecular signals used to induce differentiation of stem cells into the
      osteoblastic lineage, which ultimately leads to active bone formation; and (5)
      the mechanical stimulation protocols used to maintain the integrity of the bone
      repair and their role in successful cell engraftment. Finally, a couple clinical
      scenarios are presented (non-unions and avascular necrosis-AVN), to illustrate
      how novel cell-based therapy approaches can be used. A thorough understanding of
      tissue engineering and cell-based therapies may allow for better incorporation of
      these potential therapeutic approaches in bone defects allowing for proper bone
      repair and regeneration.

PMID- 30109234
TI  - Network Architecture and Mutational Sensitivity of the C. elegans Metabolome.
AB  - A fundamental issue in evolutionary systems biology is understanding the
      relationship between the topological architecture of a biological network, such
      as a metabolic network, and the evolution of the network. The rate at which an
      element in a metabolic network accumulates genetic variation via new mutations
      depends on both the size of the mutational target it presents and its robustness
      to mutational perturbation. Quantifying the relationship between topological
      properties of network elements and the mutability of those elements will
      facilitate understanding the variation in and evolution of networks at the level
      of populations and higher taxa. We report an investigation into the relationship
      between two topological properties of 29 metabolites in the C. elegans metabolic
      network and the sensitivity of those metabolites to the cumulative effects of
      spontaneous mutation. The correlations between measures of network centrality and
      mutability are not statistically significant, but several trends point toward a
      weak positive association between network centrality and mutational sensitivity.
      There is a small but significant negative association between the mutational
      correlation of a pair of metabolites (rM ) and the shortest path length between
      those metabolites. Positive association between the centrality of a metabolite
      and its mutational heritability is consistent with centrally-positioned
      metabolites presenting a larger mutational target than peripheral ones, and is
      inconsistent with centrality conferring mutational robustness, at least in toto.
      The weakness of the correlation between rM and the shortest path length between
      pairs of metabolites suggests that network locality is an important but not
      overwhelming factor governing mutational pleiotropy. These findings provide
      necessary background against which the effects of other evolutionary forces, most
      importantly natural selection, can be interpreted.

PMID- 30109232
TI  - Mineral and Bone Disorders After Kidney Transplantation.
AB  - The risk of mineral and bone disorders among patients with chronic kidney disease
      is substantially elevated, owing largely to alterations in calcium, phosphorus,
      vitamin D, parathyroid hormone, and fibroblast growth factor 23. The interwoven
      relationship among these minerals and hormones results in maladaptive responses
      that are differentially affected by the process of kidney transplantation.
      Interpretation of conventional labs, imaging, and other fracture risk assessment
      tools are not standardized in the post-transplant setting. Post-transplant bone
      disease is not uniformly improved and considerable variation exists in monitoring
      and treatment practices. A spectrum of abnormalities such as hypophosphatemia,
      hypercalcemia, hyperparathyroidism, osteomalacia, osteopenia, and osteoporosis
      are commonly encountered in the post-transplant period. Thus, reducing fracture
      risk and other bone-related complications requires recognition of these
      abnormalities along with the risk incurred by concomitant immunosuppression use.
      As kidney transplant recipients continue to age, the drivers of bone disease vary
      throughout the post-transplant period among persistent hyperparathyroidism, de
      novo hyperparathyroidism, and osteoporosis. The use of anti-resorptive therapies
      require understanding of different options and the clinical scenarios that
      warrant their use. With limited studies underscoring clinical events such as
      fractures, expert understanding of MBD physiology, and surrogate marker
      interpretation is needed to determine ideal and individualized therapy.

PMID- 30109235
TI  - Cerebrovascular Events After Transcatheter Aortic Valve Implantation.
AB  - Transcatheter aortic valve implantation (TAVI) has emerged as an alternative less
      invasive treatment for patients with symptomatic severe aortic stenosis. Despite
      the technological development and knowledge improvement in recent years,
      neurological complications remain a concern, especially with the expansion of the
      technique toward younger and lower risk patients. Clinical cerebrovascular events
      have an important impact on patients' morbidity and mortality with a
      multifactorial origin. While cerebral microembolizations during TAVI is a
      universal phenomenon and embolic protection devices have been developed in an
      attempt to reduce them, their clinical utility remains unclear. We review the
      current evidence on cerebrovascular events associated with TAVI and potential
      preventive strategies.

PMID- 30109236
TI  - Effects of Edible Treats Containing Ascophyllum nodosum on the Oral Health of
      Dogs: A Double-Blind, Randomized, Placebo-Controlled Single-Center Study.
AB  - The objective of this placebo-controlled, double-blind, randomized study
      (designed according to evidence based medicine standards) was to determine the
      effect of 90-day administration of edible treats containing the brown algae,
      Ascophyllum nodosum, on plaque and dental calculus accumulation on the teeth of
      dogs, as well as on other parameters characterizing canine oral health status,
      including: plaque index (PI), calculus index (CI), oral health index (OHI),
      gingival bleeding index (GBI), and volatile sulfur compound (VSC) concentration.
      Sixty client-owned dogs, including Japanese chin, miniature Schnauzer, Chihuahua,
      Pomeranian, and West Highland White Terrier (WHWT) breeds, underwent professional
      dental cleaning and were randomly subdivided into two groups receiving daily
      edible treats containing the brown algae A. nodosum, or placebo, adjusted to
      their bodyweight. After a comprehensive oral health assessment, including a
      professional dental cleaning, which were both performed under general anesthesia,
      clinical assessments of PI, CI, OHI, GBI, and VSC concentration were performed
      under sedation after 30, 60, and 90 days of treatment. Oral administration of
      edible treats containing A. nodosum significantly improved PI, CI, and VSC
      concentration, compared with the placebo-treated group. The consumption of edible
      treats containing A. nodosum efficiently decreased plaque and calculus
      accumulation in the investigated dogs. Dogs treated with A. nodosum also
      exhibited significantly lower concentrations of VSC and better oral health status
      (e.g., OHI and GBI) than those in the placebo-control group.

PMID- 30109237
TI  - Return to Play Among Elite Basketball Players After Osteochondral Allograft
      Transplantation of Full-Thickness Cartilage Lesions.
AB  - Background: Osteochondral allograft transplantation (OCA) is a recognized option
      for full-thickness articular cartilage defects of the knee, especially in the
      setting of large lesions or those involving the subchondral bone. Previous
      heterogenous studies of athletes have shown a 75% to 79% rate of return to play
      after the procedure. Purpose: To define return-to-play rates in a cohort of elite
      collegiate and professional basketball players following osteochondral allograft
      of the knee. Study Design: Case series; Level of evidence, 4. Methods:
      Prospectively collected data from an institutional cartilage repair registry were
      retrospectively reviewed. Patients were eligible for inclusion if they were
      collegiate or professional basketball players at the time of surgery. Patient
      demographics, lesion size and location, and surgical details were collected.
      Postoperative magnetic resonance imaging scans were scored with the OCAMRISS
      system. Time to return to play and pre- versus postoperative player performance
      were determined with publicly available internet resources. Results: Eleven
      athletes (4 professional, 7 collegiate) with a total of 14 treated lesions (1 to
      the medial femoral condyle, 6 to the lateral femoral condyle, 5 to the trochlea,
      and 2 to the patella) were eligible for study inclusion. Mean lesion size was 509
      mm2. All patients underwent OCA through an arthrotomy, with fresh grafts. The
      overall rate of return to play at the same level of competition was 80%. Median
      time to return to play was 14 months (range, 6-26 months). Among players with
      available statistics, there was no significant reduction in any performance
      category. Conclusion: OCA in elite basketball players results in an 80% return to
      previous level of competition, which is consistent with previous reports of
      athletes playing other sports. Osteochondral allografting is a reasonable option
      to consider for full-thickness cartilage lesions of the knee, even for elite
      jumping athletes.

PMID- 30109238
TI  - Bone Bruises in Children and Adolescents Are Not Associated With Ligament
      Ruptures.
AB  - Background: Clinical characteristics of uncomplicated bone bruises (ie, not
      associated with a ligament rupture, meniscal tear, or fracture of the knee) in
      young athletes have scarcely been reported. Purpose: To identify mechanisms of
      injury, characterize bone bruise patterns, and identify clinical factors relating
      to recovery in young patients suffering uncomplicated bone bruises about the
      knee. Study Design: Case series; Level of evidence, 4. Methods: A review of
      clinical records and magnetic resonance imaging (MRI) findings of patients seen
      at a single institution was completed. Results: We identified 62 children and
      teenagers (mean age, 13.9 years; range, 8-18 years) who had a total of 101 bone
      bruises on MRI. The injuries occurred during a variety of organized and
      recreational sporting activities, the most common being football, basketball, and
      soccer. The majority (61.4%) of bone bruises occurred as a result of noncontact
      mechanisms. Patients reported a mean pain scale score of 6.3 of 10 (range, 2-10)
      on presentation. Frequent clinical findings included non-joint-line tenderness
      (64.5%), limited range of motion (58.1%), joint-line tenderness (54.8%), and
      positive meniscal signs (50.0%). The majority of bone bruises (61.4%) were
      located medially, and the most common bone bruise type was subcortical (58.4%),
      followed by medullary/reticular (35.6%) and articular impaction (5.9%). The only
      factor related to time to recovery was mechanism of injury; patients reporting a
      noncontact mechanism required significantly more time to recover than those
      reporting a contact mechanism (mean, 99.7 +/- 74.8 vs 65.7 +/- 38.8 days,
      respectively; F = 3.753, P = .049). Conclusion: In this case series of 62
      pediatric patients with non-anterior cruciate ligament (ACL) bone bruises, the
      majority occurred in the medial compartment, suggesting that these bone bruises
      result from a mechanism distinct from the pivot-shift mechanism, classically
      thought to cause ACL injuries.

PMID- 30109239
TI  - Prevalence of Posttraumatic Stress Disorder Symptoms Among Young Athletes After
      Anterior Cruciate Ligament Rupture.
AB  - Background: The risk of depression and the fear of reinjury were documented in
      recent investigations of patients after anterior cruciate ligament (ACL)
      ruptures. The extent of psychological trauma accompanying these injuries among
      young athletes, however, has never been assessed. Hypothesis: Posttraumatic
      stress disorder (PTSD) symptoms after ACL injury are present among young athletes
      with high athletic identities. Study Design: Case series; Level of evidence, 4.
      Methods: Patients <=21 years of age who had suffered an acute ACL rupture were
      consecutively recruited at a tertiary care center. Patients completed the
      Horowitz Impact of Event Scale - Revised (IES-R) to analyze for PTSD
      symptomatology, the Athletic Identity Measurement Scale, and an athlete
      specialization instrument created at the authors' institution. Results: A total
      of 24 patients were consecutively recruited. The mean patient age was 14.5 +/-
      2.7 years, and 50% of patients were male. More than 87.5% of patients experienced
      avoidance symptoms, 83.3% acknowledged symptoms of intrusion, and 75% had
      symptoms of hyperarousal. Patients aged 15 to 21 years incurred a higher severity
      of PTSD symptoms than younger patients (P = .033). Female patients experienced
      greater emotional trauma than male patients (P = .017). Finally, patients with
      high athletic identities experienced greater emotional trauma than those with
      lesser athletic identities, but this finding was not statistically significant (P
      = .14). Conclusion: Following ACL rupture, young athletes experience significant
      emotional trauma, including symptoms of avoidance, intrusion, and hyperarousal.
      High school and college athletes, female athletes, and patients with high
      athletic identities may be most susceptible.

PMID- 30109240
TI  - Hyperflexion and Femoral Interference Screw Insertion in ACL Reconstruction.
AB  - Background: In anatomic anterior cruciate ligament (ACL) reconstructions produced
      with flexible reamers and no knee hyperflexion, it is unknown whether knee
      hyperflexion is necessary for femoral interference screw insertion. Purpose: To
      compare femoral screw-graft divergence in anatomic ACL reconstructions with
      endoscopic interference screws placed without knee hyperflexion and with the use
      of flexible versus rigid screwdrivers. Study Design: Controlled laboratory study.
      Methods: Ten matched pairs of cadaveric knees had bone-tendon-bone graft ACL
      reconstructions with anatomic femoral tunnels. The knees were flexed to 90
      degrees . Femoral interference screws (7 * 20 mm) were placed in pairs of knees:
      in 1 knee with a flexible screwdriver and in the opposite knee with a rigid
      screwdriver. Graft-screw divergence was imaged with computed tomography scans and
      tested with cyclic and static biomechanical tests. Results: The mean screw-graft
      divergence was 12.07 degrees  +/- 4.04 degrees  with the rigid screwdriver and
      10.68 degrees  +/- 3.23 degrees  with the flexible screwdriver (P = .35). The
      cyclic tests with screws placed by a rigid screwdriver had a mean increase in
      displacement of 0.56 +/- 0.20 mm. For screws placed with the flexible
      screwdriver, the mean increase in displacement was 0.58 +/- 0.32 mm (P = .66).
      Yield load was 393.3 +/- 95.1 N for screws placed by a rigid screwdriver and
      408.2 +/- 119.0 N for screws inserted with the flexible screwdriver (P = .78).
      Maximum load was 523.1 +/- 88.7 N for screws placed by a rigid screwdriver and
      467.1 +/- 107.3 N for screws inserted with the flexible screwdriver (P = .09).
      Conclusion: With either a rigid or a flexible screwdriver, there were no
      significant effects on screw divergence or fixation strength. Clinical Relevance:
      Knees can be kept at 90 degrees  during endoscopic femoral interference screw
      insertion. The use of a traditional rigid or flexible screwdriver will not affect
      screw-graft divergence or fixation strength.

PMID- 30109241
TI  - Increasing Rates of Invasive Group A Streptococcal Disease in Alberta, Canada;
      2003-2017.
AB  - Background: We present an analysis of increasing rates of invasive group A
      streptococci (iGAS) over a 15-year period in Alberta, Canada. Methods: From 2003
      to 2017, the emm type of iGAS isolates was identified from patients with iGAS
      disease in Alberta. Demographic, clinical, and risk factor data were collected.
      Results: A total of 3551 cases of iGAS were identified in Alberta by isolation of
      a GAS isolate from a sterile site. The age-standardized incidence rates of iGAS
      increased from 4.24/100 000 in 2003 to 10.24 in 2017. Rates (SD) were highest in
      those age <1 (9.69) years and 60+ (11.15) years; 57.79% of the cases were male.
      Commonly identified risk factors included diabetes, hepatitis C, nonsurgical
      wounds, addiction, alcohol abuse, drug use, and homelessness. The overall age
      standardized case fatality rate was 5.11%. The most common clinical presentation
      was septicemia/bacteremia (41.84%), followed by cellulitis (17.25%). The top 4
      emm types from 2003-2017 were emm1, 28, 59, and 12. In 2017, the top 4 emm types
      (emm1, 74, 101, and 59) accounted for 46.60% of cases. Conclusions: The incidence
      of iGAS disease in Alberta, Canada, has increased from 2003 to 2017. This
      increase has been driven not by a single emm type, but rather what has been
      observed is a collection of common and emerging emm types associated with
      disease. In addition, it is also likely that societal factors are playing
      important roles in this increase as risk factors associated with marginalized
      populations (addiction, alcohol abuse, and drug use) were found to have increased
      during the survey period.

PMID- 30109243
TI  - Vascularized bone graft from the second metacarpal base for trapeziometacarpal
      joint arthrodesis.
AB  - Three female patients underwent TMC joint arthrodesis using a vascularized bone
      graft from the second metacarpal base. Surgical indications were nonunion after
      failed TMC joint arthrodesis and osteoarthritis and severe osteoporosis. All
      cases achieved early bone union, and marked postoperative improvement in the VAS
      and DASH scores.

PMID- 30109244
TI  - Management of second metacarpal chronic osteomyelitis by induced membrane
      technique.
AB  - Management of chronic osteoarticular infection of the hand is a true challenge.
      Several methods of treatment are described in the literature to eradicate the
      infection. We present a case in which chronic osteomyelitis of the second
      metacarpal was treated by induced membrane technique, with successful outcome and
      complete hand recovery.

PMID- 30109242
TI  - Efficient Gene Transfer to the Central Nervous System by Single-Stranded
      Anc80L65.
AB  - Adeno-associated viral vectors (AAVs) have demonstrated potential in applications
      for neurologic disorders, and the discovery that some AAVs can cross the blood
      brain barrier (BBB) after intravenous injection has further expanded these
      opportunities for non-invasive brain delivery. Anc80L65, a novel AAV capsid
      designed from in silico reconstruction of the viral evolutionary lineage, has
      previously demonstrated robust transduction capabilities after local delivery in
      various tissues such as liver, retina, or cochlea, compared with conventional
      AAVs. Here, we compared the transduction efficacy of Anc80L65 with conventional
      AAV9 in the CNS after intravenous, intracerebroventricular (i.c.v.), or
      intraparenchymal injections. Anc80L65 was more potent at targeting the brain and
      spinal cord after intravenous injection than AAV9, and mostly transduced
      astrocytes and a wide range of neuronal subpopulations. Although the efficacy of
      Anc80L65 and AAV9 is similar after direct intraparenchymal injection in the
      striatum, Anc80L65's diffusion throughout the CNS was more extensive than AAV9
      after i.c.v. infusion, leading to widespread EGFP expression in the cerebellum.
      These findings demonstrate that Anc80L65 is a highly efficient gene transfer
      vector for the murine CNS. Systemic injection of Anc80L65 leads to notable
      expression in the CNS that does not rely on a self-complementary genome. These
      data warrant further testing in larger animal models.

PMID- 30109245
TI  - Breast biopsy navigation system with an assisted needle holder tool and 2D
      graphical user interface.
AB  - Objective: This paper proposes the development of a breast biopsy navigation
      system with an assisted needle holder tool for a coaxial needle and a graphical
      user interface, which utilizes an optical tracking device to localize the needle
      position relative to the ultrasound image with the aim to improve performance
      especially for a new radiologist or an inexperienced group. Materials and
      methods: The system consists of an assisted needle holder tool, which as an
      attachment for the 2D ultrasound transducer and the graphical user interface
      (GUI) that shows the needle pathway, needle line and warning signs. An optical
      tracking system is used to track the needle motion, ultrasound image and
      transform all information to with respect to the technique. The system is
      evaluated using a phantom made from gel candle. There were nine experienced and
      eight inexperienced participants who performed the breast biopsy intervention,
      using three methods: the freehand method, only the needle holder tool guidance,
      and the whole navigation guidance (GUI + assisted needle holder). Results: The
      results demonstrate a success rate of over 90% using only assisted needle holder
      and the whole system to perform breast biopsy for the experienced and
      inexperienced groups, whereas for the inexperienced group a success rate of 57.5%
      was achieved using the freehand method. The use of only assisted needle holder
      for breast biopsy reduces the time for a procedure in the inexperienced group by
      6 s when compared to the freehand method. Conclusion: The authors believe that
      this navigation system can be applied in a clinical setting and give an advantage
      to inexperienced radiologists who must successfully perform clinical breast
      biopsy.

PMID- 30109247
TI  - Data on entrepreneurship education and entrepreneurial performance of aspiring
      entrepreneurs in selected Nigerian universities.
AB  - Entrepreneurs are individuals who have a constant feeling of desperation that is
      from time to time seen in organizations. While the number of entrepreneurship
      education programmes are increasing, their impact is under-researched and studies
      paint an unclear picture of the impact of entrepreneurship education. This
      present study presents data on the extent to which university entrepreneurship
      education programmes stimulate the entrepreneurial performance of aspiring
      entrepreneurs in Nigeria. Data was collected using a descriptive cross-sectional
      quantitative survey conducted among university students (N = 540) of selected
      institutions in Nigeria. Regression Analysis was used in confirming the
      hypotheses proposed in the study using the Statistical Package for Social
      Sciences (SPSS) version 22. University entrepreneurship education is confirmed to
      be a major source of inspirational triggers that positively impact on
      entrepreneurial performance of aspiring entrepreneurs in the selected
      universities in Nigeria. The field data set is made widely accessible to allow
      for critical inquiry.

PMID- 30109246
TI  - Survey dataset on the types, prevalence and causes of deviant behavior among
      secondary school adolescents in some selected schools in Benin City, Edo State,
      Nigeria.
AB  - This data article contains the exploratory analysis of data obtained from a field
      survey done to determine the types, prevalence and likely causes of deviant
      behaviors among secondary schools' adolescents in some selected schools in Benin
      City. The data presents the findings in tables and will be helpful in childcare
      guidance, counseling, education management and for education policy makers.

PMID- 30109248
TI  - Callus and etiolation induction data from explants of Solanecio biafrae (Olive &
      Hierne) C. Jeffrey cultured in the dark.
AB  - Different types of explant (leaf, nodal and petiole explant) from in vitro grown
      plant maintained on Murashige and Skoog (MS) medium, were cultured on MS medium
      supplemented with various concentrations of 2, 4-Dichlorophenoxy acetic acid(2, 4
      D) (0, 0.5, 1.0, 1.5 and 2.0 mg/l) in dark condition. Data on callus formation
      was recorded on 10 days after culture. Number of explants forming callus, callus
      colour and type were recorded. The plant growth regulator-free media which served
      as the control induced etiolation resulting in long hypocotyls from the nodal
      explants.

PMID- 30109249
TI  - Survey dataset on factors that influence satisfaction of clients with
      architectural services in Lagos State, Nigeria.
AB  - The retention of clients of professional service practitioners is often dependent
      on their satisfaction with the services they obtain. This article presents data
      on the factors that influence the satisfaction of clients with architectural
      services in Lagos State, Nigeria. Data were obtained from a cross-sectional
      survey research, which adopted random sampling of clients from six estates in the
      State. The questionnaire was used as an instrument for the survey. The response
      rate was 81.3%. The dataset is made available in tables and charts of frequencies
      and means. The data are of interest to researchers in the professional service
      organisation, management and those in the decision sciences. The data could also
      be of interest to practitioners who may further analyse the data to develop
      business strategies to satisfy their clients.

PMID- 30109250
TI  - Effects on tumor growth and immunosuppression of a modified Talpha1 peptide along
      with its circular dichroism spectroscopy data.
AB  - The data presented in this article are related to the research article entitled
      "Immunomodulatory and Enhanced Antitumor Activity of a Modified Thymosin alpha1
      in Melanoma and Lung Cancer" (Wang et al., 2018). Talpha1 has been evaluated as
      effective in cancer treatment. In order to make it capable to target tumor, a
      peptide iRGD was introduced to Talpha1. The anti-tumor activity was accessed by
      constructing in vivo melanoma and human non-small-cell lung cancer models treated
      with Talpha1-iRGD to measure the tumor volume over time and tumor weight at the
      last day. The concentration of IFN-gamma and IL-2 in C57BL/6 mice peripheral
      blood was determined by ELISA. And the immunomodulatory ability of Talpha1-iRGD
      was evaluated in vivo by thymus index and spleen index. Those functions this
      paper was aimed at may have relationship with its secondary structure, so the
      circular dichroism spectra of Talpha1, iRGD and Talpha1-iRGD was performed.

PMID- 30109251
TI  - Development and optimisation data of a tissue digestion method for the isolation
      of orthopaedic wear particles.
AB  - The data contained within this article relate to several enzymatic tissue
      digestion experiments which were performed to produce an optimised protocol for
      the digestion of tissue samples. The digestion experiments involved a total of
      four different digestion protocols. The first protocol involved digestion with
      proteinase K, without the use of glycine. The second protocol involved digestion
      with proteinase K in the presence of glycine. The third protocol consisted of
      proteinase K digestion in the presence of glycine, with more frequent enzyme
      replenishment. The final protocol was similar to the third protocol but included
      a papain digestion stage prior to digestion with proteinase K. The data contained
      within this article are photographs of tissue samples which were captured at key
      stages of the four protocols and written descriptions based on visual observation
      of the tissue samples, which document the appearance of the tissue digests.

PMID- 30109252
TI  - Gankyrin Promotes Tumor-Suppressor Protein Degradation to Drive Hepatocyte
      Proliferation.
AB  - Background & Aims: Uncontrolled liver proliferation is a key characteristic of
      liver cancer; however, the mechanisms by which this occurs are not well
      understood. Elucidation of these mechanisms is necessary for the development of
      better therapy. The oncogene Gankyrin (Gank) is overexpressed in both
      hepatocellular carcinoma and hepatoblastoma. The aim of this work was to
      determine the role of Gank in liver proliferation and elucidate the mechanism by
      which Gank promotes liver proliferation. Methods: We generated Gank liver
      specific knock-out (GLKO) mice and examined liver biology and proliferation after
      surgical resection and liver injury. Results: Global profiling of gene expression
      in GLKO mice showed significant changes in pathways involved in liver cancer and
      proliferation. Investigations of liver proliferation after partial hepatectomy
      and CCl4 treatment showed that GLKO mice have dramatically inhibited
      proliferation of hepatocytes at early stages after surgery and injury. In control
      LoxP mice, liver proliferation was characterized by Gank-mediated reduction of
      tumor-suppressor proteins (TSPs). The failure of GLKO hepatocytes to proliferate
      is associated with a lack of down-regulation of these proteins. Surprisingly, we
      found that hepatic progenitor cells of GLKO mice start proliferation at later
      stages and restore the original size of the liver at 14 days after partial
      hepatectomy. To examine the proliferative activities of Gank in cancer cells, we
      used a small molecule, cjoc42, to inhibit interactions of Gank with the 26S
      proteasome. These studies showed that Gank triggers degradation of TSPs and that
      cjoc42-mediated inhibition of Gank increases levels of TSPs and inhibits
      proliferation of cancer cells. Conclusions: These studies show that Gank promotes
      hepatocyte proliferation by elimination of TSPs. This work provides background
      for the development of Gank-mediated therapy for the treatment of liver cancer.
      RNA sequencing data can be accessed in the NCBI Gene Expression Omnibus:
      GSE104395.

PMID- 30109254
TI  - The use of a suture retention device to enhance tissue expansion and healing in
      the repair of scalp and lower leg wounds.

PMID- 30109255
TI  - Infantile-onset palmo-plantar basal cell carcinomas and pits in Gorlin syndrome.

PMID- 30109253
TI  - Epithelial Smad4 Deletion Up-Regulates Inflammation and Promotes Inflammation
      Associated Cancer.
AB  - Background & Aims: Chronic inflammation is a predisposing condition for
      colorectal cancer. Many studies to date have focused on proinflammatory signaling
      pathways in the colon. Understanding the mechanisms that suppress inflammation,
      particularly in epithelial cells, is critical for developing therapeutic
      interventions. Here, we explored the roles of transforming growth factor beta
      (TGFbeta) family signaling through SMAD4 in colonic epithelial cells. Methods:
      The Smad4 gene was deleted specifically in adult murine intestinal epithelium.
      Colitis was induced by 3 rounds of dextran sodium sulfate in drinking water,
      after which mice were observed for up to 3 months. Nontransformed mouse
      colonocyte cell lines and colonoid cultures and human colorectal cancer cell
      lines were analyzed for responses to TGFbeta1 and bone morphogenetic protein 2.
      Results: Dextran sodium sulfate treatment was sufficient to drive carcinogenesis
      in mice lacking colonic Smad4 expression, with resulting tumors bearing striking
      resemblance to human colitis-associated carcinoma. Loss of SMAD4 protein was
      observed in 48% of human colitis-associated carcinoma samples as compared with
      19% of sporadic colorectal carcinomas. Loss of Smad4 increased the expression of
      inflammatory mediators within nontransformed mouse colon epithelial cells in
      vivo. In vitro analysis of mouse and human colonic epithelial cell lines and
      organoids indicated that much of this regulation was cell autonomous.
      Furthermore, TGFbeta signaling inhibited the epithelial inflammatory response to
      proinflammatory cytokines. Conclusions: TGFbeta suppresses the expression of
      proinflammatory genes in the colon epithelium, and loss of its downstream
      mediator, SMAD4, is sufficient to initiate inflammation-driven colon cancer.
      Transcript profiling: GSE100082.

PMID- 30109256
TI  - Standard and optimal cut-off values of serum ca-125, HE4 and ROMA in preoperative
      prediction of ovarian cancer in Vietnam.
AB  - Objectives: To evaluate the validity of serum CA-125, Human Epididymis protein 4
      (HE4) and Risk of Malignancy Algorithm (ROMA) at standard and optimal cut-offs,
      in preoperative prediction of epithelial ovarian carcinoma (EOC) in Vietnam.
      Subjects and methods: Cross-sectional, descriptive study on 277 patients with
      ovarian masses hospitalized at the OBGYN Departments, Hue University Hospital and
      Hue Central Hospital, Vietnam, from 01/2016 to 11/2017. All patients had
      measurements of serum CA-125 by Elecsys 2010 system and HE4 by immunoassay
      ARCHITECT(r) HE4 kits; ROMA calculated, and preoperative malignancy risk
      estimated. Matching these values to postoperative histopathology resulted in the
      preoperative prediction values. Results: There were 30 (10.8%) cases of EOC.
      Median values of CA 125, HE4, and ROMA of EOC and benign tumors were 214.20 U/ml,
      18.91 U/ml; 90.00 pmol/l, 39.80 pmol/l; and 55.20%, 4.80%, respectively. The
      sensitivities and specificity of CA125, HE4, and ROMA to distinguish between
      malignant and benign tumors at standard cut-offs were 83.3% and 78.5%; 50% and
      98.38%; 80.0% and 84,6%, and those at optimal cut-offs were 83.3% and 86.6%;
      80.0% and 91.5%, 86.7% and 88.7%, respectively. AUCs of CA-125, HE4, and ROMA
      were 0.872, 0.894, 0.912; and those for the post-menopausal group were 0.900,
      0.894 and 0.924, respectively. Conclusion: Serum CA 125 and HE4 levels and ROMA
      have good validity in the diagnosis of EOC, of which ROMA gives the best result.
      The ROMA index should be applied in clinical practice to help in the assessment
      and management of patients with suspected ovarian cancer.

PMID- 30109257
TI  - All-cause mortality, age at arrival, and duration of residence among adult
      migrants in Sweden: A population-based longitudinal study.
AB  - Background: A mortality advantage has been observed among recently arrived
      immigrants in multiple national contexts, even though many immigrants experience
      more social disadvantage compared to natives. This is the first study to
      investigate the combined influence of duration of residence and age at arrival on
      the association between region of origin and all-cause mortality among the adult
      immigrant population in Sweden. Methods: Using population-based registers, we
      conducted a follow-up study of 1,363,429 individuals aged 25-64 years from 1990
      to 2008. Gompertz parametric survival models were fitted to derive hazard ratios
      (HR) for all-cause mortality. Results: Compared to native Swedes, we observed a
      health advantage in all group of immigrants, with the exception of individuals
      from Finland. However, when information on age at arrival and duration of
      residence was combined, an excess mortality risk was found among immigrants who
      arrived before age 18, which largely disappeared after 15 years of residence in
      Sweden. Non-European immigrants over age 18 showed similar or lower mortality
      risks than natives in all categories of age at arrival, regardless of duration of
      residence. Conclusions: The findings suggest that the mortality advantage
      commonly observed among immigrants is not universal. Combined information on age
      at arrival and duration of residence can be used to identify sensitive periods
      and to identify possible selection bias. The study also suggests that young
      immigrants are a vulnerable subpopulation. Given the increased number of
      unaccompanied minors arriving in Europe, targeted health or integration policies
      should be developed or reviewed.

PMID- 30109258
TI  - A psychometric evaluation of the Protective Behavioral Strategies Scale-20 among
      internet samples of adult drinkers.
AB  - Protective behavioral strategies (PBS) are most commonly defined as behaviors
      that are used while drinking to reduce alcohol use and/or limit alcohol-related
      problems. Few studies have examined and quantified PBS use among non-college
      student populations. The purpose of the present two studies was to evaluate the
      psychometric properties of the Protective Behavioral Strategies Scale-20 (PBSS
      20; Treloar, Martens, & McCarthy, 2015) among internet samples of adult drinkers.
      In the first study, we conducted an exploratory factor analysis of the PBSS-20
      with a sample (n = 360) of adult drinkers who were recruited from Mechanical
      Turk. We then conducted a second study that recruited adult drinkers from
      Mechanical Turk and randomly split the data in half. With the first split-half
      sample (n = 339), we conducted a confirmatory factor analysis of the PBSS-20 and
      assessed the internal consistency and concurrent validity of the subscales. With
      the second split-half sample (n = 338), we tested measurement invariance across
      gender. The results support a three-factor structure of the PBSS-20 that is
      similar to what has been found among college students. However, six items were
      dropped and two Serious Harm Reduction items loaded best onto the Manner of
      Drinking factor. Furthermore, two subscales demonstrated adequate internal
      consistency and all three subscale were negatively associated with alcohol
      related outcomes. Similar to college students, there was lack of measurement
      invariance across gender. We discuss the implications of the present findings in
      extending research on PBS to the more general population of U.S. adult drinkers.

PMID- 30109259
TI  - Overexpression of microRNA-34a Attenuates Proliferation and Induces Apoptosis in
      Pituitary Adenoma Cells via SOX7.
AB  - Pituitary adenomas constitute one of the most common intracranial tumors and are
      typically benign. However, the role of the tumor suppressor microRNA-34a (miR
      34a), which is implicated in other cancers, in pituitary adenoma pathogenesis
      remains largely unknown. miR-34a expression was compared between GH4C1 cancer
      cells and normal cells derived from the pituitary gland of Rattus norvegicus, and
      the effects of miR-34a on GH4C1 cell proliferation and apoptosis were examined.
      miR-34a target genes were identified and analyzed computationally. The mRNA
      levels of the miR-34a target genes were measured using qRT-PCR, and the protein
      levels of the differentially expressed targets were assessed by western blotting.
      miR-34a expression was significantly lower in GH4C1 cells, whereas miR-34a
      overexpression significantly inhibited GH4C1 cell proliferation and promoted cell
      apoptosis though SRY-box 7 (SOX7). Our data facilitate the development of a
      better understanding of the pathogenesis and treatment of pituitary adenomas by
      elucidating the crucial role of miR-34a in the development of pituitary adenomas.

PMID- 30109261
TI  - Acceleration profiles and processing methods for parabolic flight.
AB  - Parabolic flights provide cost-effective, time-limited access to "weightless" or
      reduced gravity conditions, facilitating research and validation activities that
      complement infrequent and costly access to space. Although parabolic flights have
      been conducted for decades, reference acceleration profiles and processing
      methods are not widely available. Here we present a solution for collecting,
      analyzing, and classifying the altered gravity environments experienced during
      parabolic flights, which we validated during a Boeing 727-200F flight with 20
      parabolas. All data and analysis code are freely available. Our solution can be
      integrated with diverse experimental designs, does not depend upon accelerometer
      orientation, and allows unsupervised classification of all phases of flight,
      providing a consistent and open-source approach to quantifying gravito-inertial
      accelerations (GIA), or g levels. As academic, governmental, and commercial use
      of space advances, data availability and validated processing methods will enable
      better planning, execution, and analysis of parabolic flight experiments, and
      thus facilitate future space activities.

PMID- 30109264
TI  - These violent repeats have violent extends.

PMID- 30109260
TI  - Microstructural White Matter Abnormalities in the Dorsal Cingulum of Adolescents
      with IBS.
AB  - Alterations in fractional anisotropy (FA) have been considered to reflect
      microstructural white matter (WM) changes in disease conditions; however, no
      study to date has examined WM changes using diffusion tensor imaging (DTI) in
      adolescents with irritable bowel syndrome (IBS). The objective of the present
      study was two-fold: (1) to determine whether differences in FA, and other non-FA
      metrics, were present in adolescents with IBS compared to healthy controls using
      whole-brain, region of interest (ROI)-restricted tract-based spatial statistics
      (TBSS) and canonical ROI DTI analyses for the cingulum bundle, and (2) to
      determine whether these metrics were related to clinical measures of disease
      duration and pain intensity in the IBS group. A total of 16 adolescents with a
      Rome III diagnosis of IBS (females = 12; mean age = 16.29, age range: 11.96-18.5
      years) and 16 age- and gender-matched healthy controls (females = 12; mean age =
      16.24; age range: 11.71-20.32 years) participated in this study. Diffusion
      weighted images were acquired using a Siemens 3-T Trio Tim Syngo MRI scanner with
      a 32-channel head coil. The ROI-restricted TBSS and canonical ROI-based DTI
      analyses revealed that adolescents with IBS showed decreased FA in the right
      dorsal cingulum bundle compared to controls. No relationship between FA and
      disease severity measures was found. Microstructural WM alterations in the right
      dorsal cingulum bundle in adolescents with IBS may reflect a premorbid brain
      state or the emergence of a disease-driven process that results from complex
      changes in pain- and affect-related processing via spinothalamic and
      corticolimbic pathways.

PMID- 30109262
TI  - MiR-221/222 promote epithelial-mesenchymal transition by targeting Notch3 in
      breast cancer cell lines.
AB  - Basal-like breast cancer (BLBC) is an aggressive subtype with a strong tendency
      to metastasize. Due to the lack of effective chemotherapy, BLBC has a poor
      prognosis compared with luminal subtype breast cancer. MicroRNA-221 and -222 (miR
      221/222) are overexpressed in BLBC and associate with metastasis as well as poor
      prognosis; however, the mechanisms by which miR-221/222 function as oncomiRs
      remain unknown. Here, we report that miR-221/222 expression is inversely
      correlated with Notch3 expression in breast cancer cell lines. Notch3 is known to
      be overexpressed in luminal breast cancer cells and inhibits epithelial to
      mesenchymal transition (EMT). We demonstrate that miR-221/222 target Notch3 by
      binding to its 3' untranslated region and suppressing protein translation.
      Ectopic expression of miR-221/222 significantly promotes EMT, whereas
      overexpression of Notch3 intracellular domain attenuates the oncogenic function
      of miR-221/222, suggesting that miR-221/222 exerts its oncogenic role by
      negatively regulating Notch3. Taken together, our results elucidated that miR
      221/222 promote EMT via targeting Notch3 in breast cancer cell lines suggesting
      that miR-221/222 can serve as a potential therapeutic target in BLBC.

PMID- 30109263
TI  - Breast cancer diagnosed during pregnancy is associated with enrichment of non
      silent mutations, mismatch repair deficiency signature and mucin mutations.
AB  - Breast cancer diagnosed during pregnancy (BCP) is a rare and highly challenging
      disease. To investigate the impact of pregnancy on the biology of breast cancer,
      we conducted a comparative analysis of a cohort of BCP patients and non-pregnant
      control patients by integrating gene expression, copy number alterations and
      whole genome sequencing data. We showed that BCP exhibit unique molecular
      characteristics including an enrichment of non-silent mutations, a higher
      frequency of mutations in mucin gene family and an enrichment of mismatch repair
      deficiency mutational signature. This provides important insights into the
      biology of BCP and suggests that these features may be implicated in promoting
      tumor progression during pregnancy. In addition, it provides an unprecedented
      resource for further understanding the biology of breast cancer in young women
      and how pregnancy could modulate tumor biology.

PMID- 30109265
TI  - Population genealogy resource shows evidence of familial clustering for Alzheimer
      disease.
AB  - Objective: To show the potential of a resource consisting of a genealogy of the
      US record linked to National Veterans Health Administration (VHA) patient data
      for investigation of the genetic contribution to health-related phenotypes, we
      present an analysis of familial clustering of VHA patients diagnosed with
      Alzheimer disease (AD). Methods: Patients with AD were identified by the
      International Classification of Diseases code. The Genealogical Index of
      Familiality method was used to compare the average relatedness of VHA patients
      with AD with expected relatedness. Relative risks for AD were estimated in first-
      to fifth- degree relatives of patients with AD using population rates for AD.
      Results: Evidence for significant excess relatedness and significantly elevated
      risks for AD in relatives was observed; multiple pedigrees with a significant
      excess of VHA patients with AD were identified. Conclusions: This analysis of AD
      shows the nascent power of the US Veterans Genealogy Resource, in early stages,
      to provide evidence for familial clustering of multiple phenotypes, and shows the
      utility of this VHA genealogic resource for future genetic studies.

PMID- 30109266
TI  - Axon reflex-mediated vasodilation is reduced in proportion to disease severity in
      TTR-FAP.
AB  - Objective: To evaluate the area of the vascular flare in familial amyloid
      polyneuropathy (FAP). Methods: Healthy controls and patients with genetically
      confirmed FAP were prospectively examined, on the upper and lower limbs, for
      thermal sensitivity (Medoc TSA-II thermal analyzer) and for axon reflex-mediated
      flare. The latter was induced by iontophoresis of histamine on the forearm and
      leg on 2 different visits. We used laser Doppler imaging (LDI) to measure the
      flare area (LDIflare). Results: Six patients had FAP of variable severity; 1 had
      generalized analgesia secondary to leprosy (used as a positive control). The
      median Neurological Impairment Score-Lower Limbs (NIS-LLs) was 6 (0-27). The
      warmth detection thresholds in the feet were higher in patients (median 43
      degrees , interquartile range 39.0 degrees -47.6 degrees ) compared with controls
      (37.4 degrees , 35.3 degrees -39.2 degrees ), indicating small fiber impairment.
      On the leg, LDIflare was smaller in the patients on 2 consecutive visits
      (controls: median 13.0 and 13.3 cm2, IQR 9.7-22.8 and 8.3-16.9; patients 6.9 and
      8.0 cm2, 2.6-10.8 and 6.4-12.1; p = 0.011). LDIflare on the leg was correlated
      with NIS-LL (Spearman rank correlation 0.73, p = 0.09 on the first visit;
      Spearman rank correlation 0.85, p = 0.03 on the second visit). Conclusions: Our
      study underscores that histamine-induced axon reflex-mediated vascular flare on
      the leg is reduced in proportion to disease severity in patients with FAP.

PMID- 30109267
TI  - Noncoding repeat expansions for ALS in Japan are associated with the ATXN8OS
      gene.
AB  - Objective: To assess the contribution of noncoding repeat expansions in Japanese
      patients with amyotrophic lateral sclerosis (ALS). Methods: Sporadic ALS in
      Western countries is frequently associated with noncoding repeat expansions in
      the C9ORF72 gene. Spinocerebellar ataxia type 8 (SCA8) is another noncoding
      repeat disease caused by expanded CTA/CTG repeats in the ATXN8OS gene. Although
      the involvement of upper and lower motor neurons in SCA8 has been reported, a
      positive association between SCA8 and ALS remains unestablished. Spinocerebellar
      ataxia type 36 is a recently identified disease caused by noncoding repeat
      expansions in the NOP56 gene and is characterized by motor neuron involvement. We
      collected blood samples from 102 Japanese patients with sporadic ALS and analyzed
      the ATXN8OS gene by the PCR-Sanger sequencing method and the C9ORF72 and NOP56
      genes by repeat-primed PCR assay. Results: Three patients with ALS (3%) had
      mutations in the ATXN8OS gene, whereas no patient had a mutation in the C9ORF72
      or NOP56 gene. The mutation-positive patients were clinically characterized by
      neck weakness or bulbar-predominant symptoms. None of our patients had apparent
      cerebellar atrophy on MRI, but 2 had nonsymptomatic abnormalities in the white
      matter or putamen. Conclusions: Our finding reveals the importance of noncoding
      repeat expansions in Japanese patients with ALS and extends the clinical
      phenotype of SCA8. Three percent seems small but is still relatively large for
      Japan, considering that the most commonly mutated genes, including the SOD1 and
      SQSTM1 genes, only account for 2%-3% of sporadic patients each.

PMID- 30109269
TI  - Association study between multiple system atrophy and TREM2 p.R47H.
AB  - Objective: The triggering receptor expressed on myeloid cells 2 (TREM2) p.R47H
      substitution (rs75932628) is a risk factor for Alzheimer disease (AD) but has not
      been well studied in relation to the risk of multiple system atrophy (MSA); the
      aim of this study was to evaluate the association between the TREM2 p.R47H
      variant and the risk of MSA. Methods: A total of 168 patients with pathologically
      confirmed MSA, 89 patients with clinically diagnosed MSA, and 1,695 controls were
      included. TREM2 p.R47H was genotyped and assessed for association with MSA.
      Positive results in the Taqman genotyping assay were confirmed by Sanger
      sequencing. The primary comparison involved patients with pathologically
      confirmed MSA and controls due to the definitive MSA diagnosis in the
      pathologically confirmed series. Results: We identified TREM2 p.R47H in 3
      patients with pathologically confirmed MSA (1.79%), 1 patient with clinically
      diagnosed MSA (1.12%), and 7 controls (0.41%). Minimal AD pathology was observed
      for the pathologically confirmed MSA p.R47H carriers. For the primary comparison
      of patients with pathologically confirmed MSA and controls, risk of disease was
      significantly higher for p.R47H carriers (odds ratio [OR]: 4.39, p = 0.033). When
      supplementing the 168 pathologically confirmed patients with the 89 clinically
      diagnosed and examining the combined MSA series, the association with TREM2
      p.R47H remained significant (OR: 3.81, p = 0.034). Conclusions: Our preliminary
      results suggest that the TREM2 p.R47H substitution may be a risk factor for MSA,
      implying a link to neuroinflammatory processes, especially microglial activation.
      Validation of this finding will be important, given our relatively small sample
      size; meta-analytic approaches will be needed to better define the role of this
      variant in MSA.

PMID- 30109270
TI  - De novo DNM1L mutation associated with mitochondrial epilepsy syndrome with fever
      sensitivity.

PMID- 30109268
TI  - Impaired transmissibility of atypical prions from genetic CJDG114V.
AB  - Objective: To describe the clinicopathologic, molecular, and transmissible
      characteristics of genetic prion disease in a young man carrying the PRNP-G114V
      variant. Methods: We performed genetic, histologic, and molecular studies,
      combined with in vivo transmission studies and in vitro replication studies, to
      characterize this genetic prion disease. Results: A 24-year-old American man of
      Polish descent developed progressive dementia, aphasia, and ataxia, leading to
      his death 5 years later. Histologic features included widespread spongiform
      degeneration, gliosis, and infrequent PrP plaque-like deposits within the
      cerebellum and putamen, best classifying this as a Creutzfeldt-Jakob disease
      (CJD) subtype. Molecular typing of proteinase K-resistant PrP (resPrPSc) revealed
      a mixture of type 1 (~21 kDa) and type 2 (~19 kDa) conformations with only 2,
      rather than the usual 3, PrPSc glycoforms. Brain homogenates from the proband
      failed to transmit prion disease to transgenic Tg(HuPrP) mice that overexpress
      human PrP and are typically susceptible to sporadic and genetic forms of CJD.
      When subjected to protein misfolding cyclic amplification, the PrPSc type 2 (~19
      kDa) was selectively amplified. Conclusions: The features of genetic CJDG114V
      suggest that residue 114 within the highly conserved palindromic region (113
      AGAAAAGA-120) plays an important role in prion conformation and propagation.

PMID- 30109271
TI  - GLRA1 mutation and long-term follow-up of the first hyperekplexia family.

PMID- 30109272
TI  - Confirming TDP2 mutation in spinocerebellar ataxia autosomal recessive 23
      (SCAR23).
AB  - Objective: To address the relationship between mutations in the DNA strand break
      repair protein tyrosyl DNA phosphodiesterase 2 (TDP2) and spinocerebellar ataxia
      autosomal recessive 23 (SCAR23) and to characterize the cellular phenotype of
      primary fibroblasts from this disease. Methods: We have used exome sequencing,
      Sanger sequencing, gene editing and cell biology, biochemistry, and subcellular
      mitochondrial analyses for this study. Results: We have identified a patient in
      the United States with SCAR23 harboring the same homozygous TDP2 mutation as
      previously reported in 3 Irish siblings (c.425+1G>A). The current and Irish
      patients share the same disease haplotype, but the current patient lacks a
      homozygous variant present in the Irish siblings in the closely linked gene
      ZNF193, eliminating this as a contributor to the disease. The current patient
      also displays symptoms consistent with mitochondrial dysfunction, although levels
      of mitochondrial function in patient primary skin fibroblasts are normal.
      However, we demonstrate an inability in patient primary fibroblasts to rapidly
      repair topoisomerase-induced DNA double-strand breaks (DSBs) in the nucleus and
      profound hypersensitivity to this type of DNA damage. Conclusions: These data
      confirm the TDP2 mutation as causative for SCAR23 and highlight the link between
      defects in nuclear DNA DSB repair, developmental delay, epilepsy, and ataxia.

PMID- 30109273
TI  - The Role of High-Fidelity Team-Based Simulation in Acute Care Settings: A
      Systematic Review.
AB  - Introduction  High-fidelity team-based simulation has been identified as an
      effective way of teaching and evaluating both technical and nontechnical skills.
      Several studies have described the benefits of this modality in a variety of
      acute care settings, but a lack of standardized methodologies has resulted in
      heterogeneous findings. Few studies have characterized high fidelity simulation
      across a broad range of acute care settings and integrated the latest evidence on
      its educational and patient impact. Methods  The MEDLINE, EMBASE, Cochrane
      Library, and PsycINFO databases were searched for empirical studies from the last
      10 years, investigating high fidelity team-based simulation in surgical, trauma,
      and critical care training curricula. Results  Seventeen studies were included.
      Interventions and evaluations were comprehensively characterized for each study
      and were discussed in the context of four overarching acute care settings: the
      emergency department/trauma bay, the operating room, the intensive care unit, and
      inpatient ad hoc resuscitation teams. Conclusions  The use of high-fidelity team
      based simulation has expanded in acute care and is feasible and effective in a
      wide variety of specialized acute settings, including the emergency
      department/trauma bay, the operating room, the intensive care unit, and inpatient
      ad hoc resuscitation teams. Training programs have evolved to emphasize team
      based, multidisciplinary education models and are often conducted in situ to
      maximize authenticity. In situ simulations have also provided the opportunity for
      system-level improvement and discussions of complex topics such as social
      hierarchy. There is limited evidence supporting the impact of simulation on
      patient outcomes, sustainability of simulation efforts, or cost-effectiveness of
      training programs. These areas warrant further research now that the scope of
      utilization across acute care settings has been characterized.

PMID- 30109274
TI  - Point-of-care biliary ultrasound in the emergency department (BUSED):
      implications for surgical referral and emergency department wait times.
AB  - Background: Patients with uncomplicated biliary disease frequently present to the
      emergency department for assessment. To improve bedside clinical decision making,
      biliary point-of-care ultrasound (POCUS) in the emergency department has emerged
      as a diagnostic tool. The purpose of this study is to analyze the usefulness of
      POCUS in predicting the need for surgical intervention in biliary disease.
      Methods: A retrospective study of patients visiting the emergency department who
      received a biliary POCUS from December 1, 2016 to July 15, 2017 was performed.
      The physician interpretations of the biliary POCUS scans were collected, as well
      as data from the electronic health records including lab values, the subsequent
      use of diagnostic imaging, surgical consultation or intervention, and 28 days
      follow-up for representation or complication. Results: Two hundred and eighty
      three patients were identified as having received biliary POCUS. Of the patients
      referred to general surgery who received biliary POCUS 43% received a
      cholecystectomy. For the outcome of cholecystectomy, the finding of gallstones on
      POCUS was 55% sensitive (95% CI 40% to 70%) and 92% specific (95% CI 87% to 95%).
      A sonographic Murphy's sign was 16% sensitive (95% CI 7% to 30%) but 95% specific
      (95% CI 92% to 97%) and, gallbladder wall thickness was 18% sensitive (95% CI 9%
      to 33%) and 98% specific (95% CI 95% to 99%). Patients who received POCUS but did
      not proceed to confirmatory radiology department imaging had a shorter length of
      stay (433 min +/- 50 min vs. 309 min +/- 30 min, P<0.001). Discussion: Point-of
      care biliary ultrasound performed by emergency physicians provides timely access
      to diagnostic information. Positive findings of gallstones and increased
      gallbladder wall thickness are highly predictive of the need for surgical
      intervention, and use of POCUS is associated with shorter ER visits. Level of
      evidence: Retrospective cohort study, level III.

PMID- 30109275
TI  - Introducing high-flow nasal cannula oxygen therapy at the intermediate care unit:
      expanding the range of supportive pulmonary care.
AB  - Background: Non-invasive respiratory support is a frequent indication for
      intermediate care unit (IMCU) admission. Extending the possibilities of
      respiratory support at the IMCU with high-flow nasal cannula oxygen therapy
      (HFNC) may prevent intensive care unit (ICU) transfer and invasive ventilation.
      However, the safety and limitations of HFNC administration in the stand-alone
      IMCU setting are not yet studied. This study therefore aims to investigate to
      what extent and in which patients HFNC can safely be administered at a stand
      alone mixed surgical IMCU. Methods: A case series, using retrospectively
      collected data, was performed after the first year of introducing HFNC at a stand
      alone IMCU. The following variables were collected: indication to start HFNC,
      vital parameters and arterial blood gas measurements. Primary outcome was 30-day
      mortality. Secondary outcome was transfer to the ICU. Results: A total of 96
      admissions were included. The indications to start HFNC at the IMCU were
      predominantly pathologies of pulmonary origin (n=67, 69.8%). Less frequent
      indications were prolonged support postweaning (n=15), non-pulmonary sepsis (n=7)
      and post-trauma resuscitation (n=6). The average PaO2/FiO2ratio at start of HFNC
      was 152 (95% CI 139 to 165). 30-day mortality was 7, of which 5 were admitted
      with treatment restrictions (no ICU policy) and 2 deaths were unrelated to HFNC.
      Transfer to the ICU occurred in 18 (18.8%) admissions, of which 12 received
      invasive mechanical ventilation. Reason for ICU transfer was mainly PaO2/FiO2
      ratio<100 under maximum non-invasive treatment (n=12, 66.7%). Application of HFNC
      at the IMCU prevented 162 days of ICU admission. Discussion: Administration of
      HFNC at a stand-alone surgical IMCU may be safe as it expands the range of
      supportive possibilities and thereby reduces the need for ICU admissions.
      Pulmonary indications to start HFNC increase the risk of ICU transfer and
      mechanical ventilation. Level of evidence: Level VI.

PMID- 30109277
TI  - Hierarchical Clustering based optimal PMU placement for power system fault
      observability.
AB  - Optimal number and location of phasor measurement units (PMUs) in the power
      system networks faces challenges for achieving the full network observability
      during fault conditions. Achieving fault observability approach requires more
      constraints than normal system observability and consequently suffers from
      complex analysis and heavy computational burden for the large-scale networks. A
      new algorithm for determining the optimal PMU placement considering the network
      fault observability is introduced. The proposed algorithm is achieved through
      four stages. The first stage is achieved through the network fault simulation to
      obtain the post fault change in voltage (DeltaV) at each bus. Then, the post
      fault change in voltage (DeltaV) is used to build the network connectivity matrix
      (CM) and forming a new developed Faulted Connectivity Matrix (FCM) that describes
      the power system topology during the fault conditions. The correlation between
      the buses is obtained, in the second stage, by applying Pearson correlation
      coefficient. Hierarchical Clustering technique is given, in the third stage, to
      cluster the network into coherent zones to find the most correlated buses.
      Finally, the optimal location of the PMUs is identified within each zone based on
      simple proposed placement rules. The proposed algorithm is tested under a variety
      of fault events applied on different standard test systems. The results show the
      simplicity and the effectiveness of the proposed algorithm.

PMID- 30109276
TI  - Adaptive metabolic pattern biomarker for disease monitoring and staging of lung
      cancer with liquid biopsy.
AB  - In this manuscript, we demonstrate the applicability of a metabolic liquid biopsy
      for the monitoring and staging of patients with lung cancer. This method provides
      an unbiased detection strategy to establish a more precise correlation between
      CTC quantification and the actual burden of disease, therefore improving the
      accuracy of staging based on current imaging techniques. Also, by applying
      statistical analysis techniques and probabilistic models to the metabolic status
      and distribution of peripheral blood mononuclear cell (PBMC) populations
      "perturbed" by the presence of CTCs, a new category of adaptive metabolic pattern
      biomarker (AMPB) is described and unambiguously correlated to the different
      clinical stages of the patients. In fact, this strategy allows for classification
      of different categories of disease within a single stage (stage IV) before
      computed tomography (CT) and positron emission tomography (PET) scans and with
      lower uncertainty.

PMID- 30109278
TI  - Operating room staff and surgeon documentation curriculum improves wound
      classification accuracy.
AB  - Background: Misclassification of wounds in the operating room (OR) can adversely
      affect surgical site infection (SSI) reporting and reimbursement. This study
      aimed to measure the effects of a curriculum on documentation of surgical wound
      classification (SWC) for operating room staff and surgeons. Methods: Accuracy of
      SWC was determined by comparing SWC documented by OR staff during the original
      operation to SWC determined by in-depth chart review. Patients 18 years or older
      undergoing inpatient surgical procedures were included. Two plan-do-act-study
      (PDSA) cycles were implemented over the course of 9 months. A total of 747 charts
      were reviewed. Accuracy of SWC documentation was retrospectively assessed across
      248 randomly selected surgeries during a 5-week period prior to interventions and
      compared to 244 cases and 255 cases of post-intervention data from PDSA1 and
      PDSA2, respectively. Changes in SWC accuracy were assessed pre- and post
      intervention using the kappa coefficient. A p-value for change in agreement was
      computed by comparing pre- and post-intervention kappa. Results: Inaccurate
      documentation of surgical wound class decreased significantly following
      curriculum implementation (kappa improved from 0.553 to 0.739 and 0.757; p =
      0.001). Classification accuracy improved across all wound classes; however, class
      III and IV wounds were more frequently misclassified than class I and II wounds,
      both before and after the intervention. Conclusion: Implementation of a
      multidisciplinary documentation curriculum resulted in a significant decrease in
      SWC documentation error. Improved accuracy of SWC reporting may facilitate a
      better assessment of SSI risk in a complex patient population.

PMID- 30109279
TI  - DETECTION OF WATER-BORNE PARASITES IN DRINKING WATER OF BAGHDAD, IRAQ.
AB  - Background: Within the past few decades, there has been an increase in the number
      of water-borne disease outbreaks and emergence of newly recognized waterborne
      parasites. Several factors which contribute to the spread of these diseases
      include: water, heavy rains and agricultural residues which transfer the
      parasites to water surface from the soil. The aim of this study was to detect the
      presence of parasites in the river and drinking water of Al-Wahdaa and Al-Rasheed
      Drinking Project and household water tanks from some regions of Baghdad. Method:
      Forty samples were collected from river and drinking water of Drinking Project.
      Fifty four samples of household water tanks were collected from some regions of
      Baghdad. Results: Cryptosporidium oocyst, which was founded in river water
      samples are more than those in drinking water. Furthermore, it was existed in
      Diyala Bridge &Taha Mosque from April - August and oocyst was diagnosed by using
      of Zheil-Neelson. Wet mount slide method was applied to detect cysts of free
      living amoeba Acanthomoeba, Naegleria. The number of cysts in July and August
      were higher than other months for Drinking Project and the water tanks for all
      regions. Conclusion: These results emphasize the importance screening of the
      water to prevent possible of the spread of parasitic protozoan and that the
      cracks occurrence in drinking water pipes between the stations and houses led to
      contamination of water with the infective stage of parasites, especially in the
      areas that are near agricultural fields which polluted with the cows' waste.

PMID- 30109281
TI  - CARRIAGE OF MULTI-DRUG RESISTANT UROBACTERIA BY ASYMPTOMATIC PREGNANT WOMEN IN
      YENAGOA, BAYELSA STATE, NIGERIA.
AB  - Background: Urinary Tract Infections (UTIs) in pregnancy are associated with
      significant morbidity for both mother and baby but its early detection and
      treatments can prevent unfavorable complications in pregnancy. This study
      therefore determined the prevalence of asymptomatic bacteriuria and antimicrobial
      resistance profile of the urinary bacteria among pregnant women in Yenagoa,
      Bayelsa State, Nigeria. Materials and Methods: Mid-stream urine samples were
      collected from 201 apparently healthy pregnant women attending antenatal clinics
      in Yenagoa. The samples were analyzed and the organisms identified using standard
      microbiological methods. Haemolysin production by the organisms was screened and
      their antimicrobial susceptibility was performed using standard assay methods.
      Results: A high significant bacteriuria of 119 (59.2%) was predominantly
      recovered from the pregnant women in their second and third trimesters. The
      bacteria isolated; Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia
      coli and Staphylococcus species had 36 - 67% of haemolysin producers. The
      bacteria exhibited a very high resistance to most of the antibiotics tested but
      the resistance to ceftazidime, gentamicin and ciprofloxacin was 28 - 67%. All the
      Staphylococcus species exhibited 90% and 85% resistance to cefoxitin (methicillin
      resistant) and vancomycin respectively. An 89 - 100% of the bacteria exhibited
      multiple antibiotic resistance and 72.3% of the screened bacteria phenotypically
      expressed Extended-Spectrum Beta-lactamase production. Conclusion: The high
      prevalence of significant bacteriuria with high multi-drug resistance among the
      study pregnant women call for regular education on proper personal hygiene and
      the need for early screening for UTIs during antenatal clinics as means of
      controlling the spread of antibiotic resistant organisms and complications in
      pregnancy.

PMID- 30109280
TI  - PREVALENCE OF CRYPTOSPORIDIUM SPP. AMONG ASYMPTOMATIC HEALTHY EXPATRIATE WORKERS
      IN SHARJAH, UNITED ARAB EMIRATES.
AB  - Background: Epidemiological data on Cryptosporidium infections in the United Arab
      Emirates (UAE) is scarce. Therefore, the main objective of this study was to
      determine the prevalence of Cryptosporidium species among a community of
      expatriates in Sharjah, UAE working in different sectors, including the food
      industry, house maids and other domestic occupations. Materials and Methods: One
      hundred and thirty four stool samples were collected from asymptomatic
      individuals presenting to the Sharjah Municipality Public Health Clinic (SMPHC)
      for screening of intestinal parasites for work permission purposes between 2009
      and 2011. Demographic information such as age, sex, and country of origin was
      collected. Genomic DNA extracted from the stool samples were tested for
      Cryptosporidium species using real-time PCR (qPCR). Results: Twenty-six
      individuals (19.4%) were positive for Cryptosporidium sp. by PCR. The infection
      rate was found to be highest in Afghan nationals (33%; 3/9) compared with the
      rest of the study population; yet, no significant association existed between
      nationality and infection rate. Moreover, no association was observed between
      infection rate and gender (chi2 = 2.439; P = 0.118), nor infection rate and age
      group (chi2 = 1.219; P = 0.544). Conclusion: Infection by Cryptosporidium sp. was
      common in the study group, and further studies are needed within the native
      Emirati population before any conclusions can be made about foreigners
      potentially transmitting the parasite. Furthermore, data provided in this study
      could help determine its public and veterinary significance particularly in
      outbreaks in the country.

PMID- 30109282
TI  - INTESTINAL PARASITES, NUTRITIONAL STATUS AND COGNITIVE FUNCTION AMONG PRIMARY
      SCHOOL PUPILS IN ILE-IFE, OSUN STATE, NIGERIA.
AB  - Background: Intestinal parasites are a cause of morbidity and mortality
      throughout the world particularly in developing countries and they are common
      health problems of children. This study determined the prevalence of intestinal
      parasites among primary school children, assessed risk factors predisposing to
      infection and the nutritional status with cognitive function of the pupils.
      Materials and Methods: It was a cross sectional study and 384 pupils from six
      public primary schools in Ile-Ife were enrolled. Anthropometric measurements were
      obtained using standard procedures. The intelligence quotients of the pupils were
      assessed using the Draw-a-person- test. Stool samples were collected and
      examined. Data was processed using SPSS Inc USA version 17. Statistical analysis
      was done using frequency, percentages, tables and Pearson's chi-square was used
      to determine the association between intestinal parasites, nutritional status and
      cognitive function. Results: The prevalence of intestinal parasites in the study
      population was 24% with double infection occurring in 3.2%. Ascaris lumbricoides
      most prevalent 22.1%, Hookworm 3.4%, Hymenolepis nana 0.3%. Intestinal parasites
      were present in those that use bush and refuse dump for defeacation. The
      nutritional status of the pupils showed 95.8% normal weight, 3.6% underweight and
      0.5% overweight. In terms of cognition, 65.4% mentally deficient, 14.3% mentally
      dull and 20.3% average. Conclusion: Intestinal parasites were prevalent among
      primary school children and use of bush or refuse dump for defeacation was a risk
      factor. There was no association between intestinal parasites, nutritional status
      and cognition.

PMID- 30109283
TI  - CLINICAL PRESENTATION OF HIV-INFECTED PATIENTS IN A PSYCHIATRIC HOSPITAL IN SOUTH
      AFRICA.
AB  - Background: Africa is profoundly stricken by the HIV pandemic. People living with
      HIV/AIDS are more likely to be diagnosed with psychiatric disorders than the
      general population. We describe the prevalence of different mood and psychiatric
      disorders in HIV/AIDS infected patients with serious mental illness. Materials
      and Methods: We retrospectively sourced data from 105 patient files, at
      Weskoppies Hospital, between January 2012 and December 2016. Results: 56 patients
      had a psychotic disorder; 27 patients had a mood disorder and three patients had
      a cognitive disorder. Multiple diagnoses were observed in seven patients with a
      mood and psychotic disorder; ten patients with a psychotic and cognitive disorder
      and one patient with a mood and cognitive disorder. One patient had all three
      diagnoses. The most common medical co-morbidities were hypertension (15.24%) and
      tuberculosis (13.33%). Conclusion: Mentally ill patients who are HIV positive
      mostly present with mood and psychotic disorders. Clinicians need to be vigilant
      to detect neuropsychiatric manifestations of HIV infection to effectively manage
      and optimise treatment. This study highlights the need for further intervention
      in these vulnerable patients.

PMID- 30109284
TI  - SINGLE NUCLEOTIDE POLYMORPHISM OF ECCB5 GENE OF MYCOBACTERIUM TUBERCULOSIS
      COMPLEX ISOLATES FROM SUSPECTED PULMONARY TB PATIENTS IN SURABAYA INDONESIA.
AB  - Background: Mycobacterium tuberculosis Complex (MTBC) is a group of Mycobacterium
      that causes tuberculosis (TB). TB is an infectious disease that remains a global
      health problem. Indonesia is one of the five countries in the world where TB is
      the most prevalent and became the country with tle second largest rate of TB in
      2014 and 2015. MTBC has high pathogenicity that can cause infections in animals
      and humans. The most common route of transmission is via airborne droplet nuclei
      and contact with animals or humans infected with TB. MTBC has many virulence
      factors. One of these factors is EccB5 that is encoded by eccB5 gene. EccB5 is a
      transmembrane protein-conserved membrane protein and could play a role in
      inducing damage in host cells, macrophage infection, and may correlate with
      active disease. The characterization of eccB5 gene needs to be studied to
      determine the nucleotide sequences, which may be associated with active disease.
      The aim of this research was to analyze the nuclotide sequences of eccB5 gene of
      MTBC from suspected pulmonary tuberculosis patients, SNPs of eccB5 gene and
      possible correlation with the disease, especially in Indonesia. Materials and
      Methods: Samples were collected from the Tuberculosis Laboratory, Clinical
      Microbiology of Dr. Soetomo Hospital Surabaya Indonesia. DNA extraction used
      boiling extraction method and continued nucleic acid amplification using PCR
      techniques. Primer pairs used eccB5 SK.. The positivity of DNA specific revealed
      amplicon in 1592 bp. PCR product was sequenced by 1st Base (First BASE
      Laboratories Sdn Bhd, Selangor, Malaysia). The sequence analysis used Genetyx-Win
      version 10.0 (Genetyx Corporation, Tokyo, Japan). Results: Total isolates of
      Mycobacterium spp. were 28 and those that showed positive MTBC were 24 isolates
      and 4 nontuberculosis mycobacteria (NTM) using immunochromatographic test (ICT).
      The amount of homology from MTBC using blast NCBI was 99%-100%. Two SNPs were
      found in position c.1277 which revealed replacement of amino acid in 426 of codon
      position. Conclusion: The sequence of eccB5 gene of MTBC showed high significant
      homology, while proposed non-synoymous single nucleotide polymorphisms (nsSNP)
      may associated with clinical outcomes.

PMID- 30109285
TI  - DETECTION OF HUMAN HERPESVIRUS-8 ANTIGEN IN HIV-INFECTED PATIENTS IN EAST JAVA,
      INDONESIA.
AB  - Background: Co-infection of human herpesvirus-8 (HHV-8) in HIV-positive people
      might cause Kaposi's sarcoma. Early detection of HHV-8 may prevent the onset of
      clinical manifestations. In Indonesia, detection of HHV-8 antigen in HIV-positive
      patients has yet to be reported. The intention of this research was to examine
      the presence of HHV-8 antigen in HIV-positive patients in East Java, Indonesia.
      Material and Methods: 103 serum samples were collected from HIV-positive patients
      in Surabaya and Tulungagung, East Java, Indonesia. Serums were then tested for
      the presence of HHV-8 antigen by using sandwich ELISA. Results: Human Herpesvirus
      8 antigen was detected in 15 samples (14.5%). The presence of HHV-8 infection in
      HIV-positive patients did not present differently in males and females and among
      different age groups. Human immunodeficiency virus-positive serum samples were
      collected from 23 homosexual men, 25 intravenous drug users (IVDUs) and 52
      heterosexuals. In the male homosexual group, HHV-8 antigen was detected in 21.7%
      (5/23) of the samples, while in the intravenous drug user group (IVDUs), 16%
      (4/25) of the samples were found to have HHV-8 antigen. Conclusion: This research
      found the presence of HHV-8 antigen in 14.5% of patients in East Java, Indonesia.
      It is recommended that patients with a positive result should receive further
      examination to detect any clinical manifestations related to HHV-8 infection,
      especially in the form of Kaposi's sarcoma lesions, so that the illness can be
      appropriately managed.

PMID- 30109286
TI  - BIOIMPEDANCE MARKERS AND TUBERCULOSIS OUTCOME AMONG HIV-INFECTED PATIENTS.
AB  - Background: The changes in body composition markers (weight, fat mass, lean mass,
      and BMI) over time can be associated with TB treatment outcome among HIV-infected
      patients. The aim of this study was to investigate whether changes in fat mass
      and lean mass were associated with the treatment response among patients with HIV
      infection and pulmonary tuberculosis. Materials and Methods: This was a
      prospective cohort study. Data from HIV-infected patients commencing TB therapy
      were analyzed. This included body weight measurement using bioimpedance equipment
      at baseline, one month, and two months after starting TB treatment. Results: The
      study was conducted in 125 patients, 17 patients (13.6%) died during treatment,
      of which 5 died during the first month of treatment, 4 during the second month
      and 8 after the second month. The group of patients with good response, increased
      their weight by 1.3 kg (p <0.001) at the end of the first month of TB treatment
      and 2.6 kg in the second month (p <0.001), and body fat increase was 1.2 Kg (p
      <0.001) and 2.3 kg (p <0.001), the first and second month respectively. The group
      of patients who died had lost 2.1 kg fat mass after the first month (p <0.001)
      and 3.7 kg in the second month (p <0.001). Conclusions: Our results show that the
      weight change during TB treatment (increased fat mass) helps us predict
      therapeutic response. Weight loss during the first month of starting therapy
      should be evaluated thoroughly to identify the probable cause of treatment
      failure.

PMID- 30109287
TI  - PROPOSED GUIDELINES TO MINIMISE MULTI-DRUG RESISTANT TUBERCULOSIS TREATMENT
      DEFAULT IN A MULTI-DRUG RESISTANT UNIT OF LIMPOPO PROVINCE, SOUTH AFRICA.
AB  - Background: The increasing prevalence and incidence of Multi Drug Resistant
      Tuberculosis (MDR-TB) is as a result of the defaulting of treatment by patients.
      Worldwide, several factors that contribute to patients defaulting to tuberculosis
      treatment protocol have been identified. This paper aims to develop guidelines to
      minimise the defaulting rate of MDR-TB patients in MDR unit of Limpopo Province.
      Materials and Methods: The study was conducted using a qualitative approach.
      Tesch's open coding method of data analysis was adopted to analyse the data
      obtained. Reasoning strategies were employed in the development of the
      guidelines. These include analysis, synthesis, deductive reasoning and inductive
      reasoning. Synthesis strategy was used to construct relational statements.
      Results: The factors contributing to patients' default from MDR-TB treatment were
      identified and organized into four themes. Guidelines were developed to address
      each factor and give recommendations on possible solutions. Conclusion: The
      guidelines that were developed concluded that co-operation amongst the Department
      of Health, health practitioners, patient, and family members can help in
      preventing the defaulting of treatment.

PMID- 30109288
TI  - T CELL EPITOPES OF THE ESXA FULL GENE OF MYCOBACTERIUM TUBERCULOSIS FROM SPUTUM
      OF MDR-TB PATIENTS.
AB  - Background: In 2015, World Health Organization (WHO) discovered 10.4 million
      tuberculosis (TB) cases around the world. Multidrug-resistant tuberculosis (MDR
      TB) became a threat because it has high mortality number. There were 480,000 new
      MDR-TB cases in 2015. Based on those problems, diagnostic development to detect
      M. tuberculosis rapidly and accurately is needed. The importance of detecting
      epitope expression of esxA full gene because there was a potential of complexity
      over the protein structure and might affect the protein concentration. By knowing
      epitope prediction, there's an expectation that it can help the development of TB
      diagnostic. This research was aimed to determine the T cell epitope prediction of
      esxA full gene from MDR-TB patients. Material and Methods: Total of 24 MDR-TB
      sputum isolate from TB patients at Dr. Soetomo Hospital were collected from
      September to December 2016. Samples were confirmed as MDR-TB using GeneXpert and
      Bactec MGIT 960. Those samples tested using PCR targeted 580 bp of esxA gene and
      sequencing. Gene sequence was aligned against wild type using Bioedit program
      version 7.2.5 and NCBI BLAST. T cell epitope prediction was analyzed by GENETYX
      version 10. Results: Epitope predictions that could be obtained were IEAAAS,
      ASAIQG, VTSIHS, TKLAAA, VTGMFA based IAd Pattern Position and EAAAS based
      Rothbard/Taylor Pattern Position. Those prediction epitopes can determine the
      severity of disease, therefore full gene of esxA could be used as diagnostic
      target. Conclusion: This research discovered five specific T cell epitope
      prediction based on IAd Pattern Position and one epitope prediction according to
      Rothbard/Taylor Pattern Position.

PMID- 30109289
TI  - ERRATA.
AB  - [This corrects the article on p. 20 in vol. 12, PMID: 29302646.].

PMID- 30109290
TI  - RABIES IN A SET OF EIGHT-WEEK OLD PUPPIES IN NIGERIA: THE NEED FOR REVIEW OF
      CURRENT DOG ANTIRABIES VACCINATION SCHEDULE.
AB  - Background: Rabies is endemic in Nigeria with clinical cases reported mainly in
      dogs and occasionally in livestock from all the geo-ecological zones of the
      country. Detection of rabies virus antigen in puppies at the age of five to ten
      weeks and in apparently healthy dogs shedding the virus in their saliva have been
      reported in some parts of Nigeria. Material and Method: This report describes a
      clinical rabies in a set of eight weeks old puppies confirmed by antigen
      detection using the direct fluorescent antibody test (DFAT), the direct rapid
      immunohistochemical test (DRIT), and RT-PCR. Results: it was positive for all
      test used including the RT-PCR which amplified at 750 bp from the gel
      electrophoresis. Conclusion: Occurrence of rabies in puppies of this age, within
      which they are acquired and owned by other unsuspecting members of the public, is
      of grave public health consequences. People that love puppies, especially
      children, who are fond of carrying and playing with them, are also faced with the
      risk of exposure to rabies. Consequently, review of the existing dog antirabies
      vaccination schedule at twelve weeks of age in Nigeria, is recommended to ensure
      effective immunization of this age group of dogs and for the overall safety of
      the vulnerable members of the public.

PMID- 30109293
TI  - Guest Editorial: The Foundation for Oral Rehabilitation (FOR) as the basis for
      this consensus conference.

PMID- 30109292
TI  - Editorial.

PMID- 30109291
TI  - DETECTION OF NON-INFLUENZA VIRUSES IN ACUTE RESPIRATORY INFECTIONS IN CHILDREN
      UNDER FIVE-YEAR-OLD IN COTE D'IVOIRE (JANUARY - DECEMBER 2013).
AB  - Background: Influenza sentinel surveillance in Cote d'Ivoire showed that 70% of
      Acute Respiratory Infections (ARI) cases remained without etiology. This work
      aims to describe the epidemiological, clinical, and virological pattern of ARI
      that tested negative for influenza virus, in children under five years old.
      Materials and Methods: one thousand and fifty nine samples of patients presenting
      influenza Like Illness (ILI) or Severe Acute Respiratory Infections (SARI)
      symptoms were tested for other respiratory viruses using multiplex RT-PCR assays
      targeting 10 respiratory viruses. Results: The following pathogens were detected
      as follows, hRV 31,92% (98/307), hRSV 24.4% (75/329), PIV 20.5% (63/307), HCoV
      229E 12,05% (37/307), hMPV 6.2% (19/307), HCoVOC43 1.0% (3/307) and EnV 1.0%
      (3/307). Among the 1,059 specimens analyzed, 917 (86.6%) were ILI samples and 142
      (23.4%) were SARI samples. The proportion of children infected with at least one
      virus was 29.8% (273/917) in ILI cases and 23.9% (34/142) in SARI cases. The most
      prevalent viruses, responsible for ILI cases were hRV with 35.89% (98/273) and
      hRSV in SARI cases with 41.2% (14/34) of cases. Among the 1,059 patients, only 22
      (2.1%) children presented risk factors related to the severity of influenza virus
      infection. Conclusion: This study showed that respiratory viruses play an
      important role in the etiology of ARI in children. For a better understanding of
      the epidemiology of ARI and improved case management, it would be interesting in
      this context to expand the surveillance of influenza to other respiratory
      viruses.

PMID- 30109294
TI  - FOR Consensus Conference - November 16 & 17, 2017.

PMID- 30109295
TI  - Diagnosis, avoidance and management of complications of implant-based treatments.
AB  - "If terms be incorrect, then statements do not accord with facts". (Confucius)
      "Words form the thread on which we string our experiences". (Aldous Huxley)
      Semantics is a term coined by Michel Breal (1832 to 1915) a Jewish German-French
      linguist referring to the Greek semantikos (= meaning) in his 1897 book, "Essai
      de semantique". He was a very gifted man: for example, he was the one who
      suggested to Pierre de Coubertin to include the marathon in the Olympic Games and
      who also, with the help of a Francophile American dental practitioner, Thomas
      William Evans, created the "Doctorat d'Universite", finally allowing American
      students to pursue their doctorate at a French university.

PMID- 30109296
TI  - Diagnosis, avoidance and management of complications of implant-based treatments.
AB  - This review provides an overview of review and consensus articles of the past 5
      years regarding surgical complications in implant dentistry. The focus in this
      article is on surgical complications occurring after implant insertion and on
      risk factors that compromise oral implant osseointegration.

PMID- 30109297
TI  - Prosthetic complications with implant prostheses (2001-2017).
AB  - AIM: To present recent data regarding prosthetic complications with implant
      prostheses and crowns as well as compare this data with data presented in a 2003
      publication. MATERIAL AND METHODS: An electronic Medline (PubMed) with MeSH terms
      search was performed, focussing on clinical studies that reported data on
      prosthetic complications associated with implant fixed complete dentures, implant
      overdentures, implant fixed partial dentures, and implant single crowns. RESULTS:
      There were nine prosthetic complications reported with implant fixed complete
      dentures, 17 with implant overdentures, four with implant fixed partial dentures,
      and six with implant single crowns. The greatest number of complications and the
      largest incidence of percentages occurred with implant overdentures. The lowest
      incidence percentages were recorded for implant single crowns. These findings are
      in agreement with the previous 2003 publication. It is of interest to note that
      some of the complications reported previously were not reported in this review,
      and some complications reported in this review were not listed in the 2003
      publication, thereby limiting the number of direct comparisons between this paper
      and the earlier report. A surprising finding was that some complications
      associated with implant overdentures from the current data exceeded the incidence
      in 2003 (reactivation of the retentive attachment; mucosal hyperplasia; and the
      need for overdenture relines). CONCLUSIONS: Implant overdentures are associated
      with more complications than implant fixed complete dentures, implant fixed
      partial dentures, and implant single crowns. The lowest incidence of
      complications was reported with implant single crowns. The most common
      complication reported with implant fixed complete dentures was denture tooth
      fracture. The most common complication associated with implant overdentures was
      the need for adjustments. Porcelain veneer fracture/chipping was the most common
      complication identified in the studies of implant fixed partial dentures. The
      most common complication reported with implant single crowns was abutment screw
      loosening.

PMID- 30109298
TI  - Foreign body reactions, marginal bone loss and allergies in relation to titanium
      implants.
AB  - AIM: To describe general observations of immunological reactions to foreign
      materials and to realize that CP titanium gives rise to a foreign body reaction
      with subsequent bone embedment when placed as oral implants. To analyse the
      possibility of titanium allergy. MATERIALS AND METHODS: The present paper is of a
      narrative review type. Hand and Medline searches were performed to evaluate
      marginal bone loss of oral implants and the potential of titanium allergy.
      RESULTS: Immunological reactions to foreign substances include Type I
      hypersensitivity reactions such as allergy, Type II hypersensitivity reactions
      characterised by IgM or IgG antibodies that may react with blood group antigens
      at transfusion, and Type III hypersensitivity caused by antigen-antibody immune
      complexes exemplified by acute serum sickness. There is also Type IV
      hypersensitivity, or delayed hypersensitivity, which is typically found in drug
      and foreign body reactions. It proved very difficult to find a universally
      acceptable definition of reasons for marginal bone loss around oral implants,
      which lead to most varying figures of so-called peri-implantitis being 1% to 2%
      in some 10-year follow-up papers to between 28% and 56% of all placed implants in
      other papers. It was recognised that bone resorption to oral as well as
      orthopaedic implants may be due to immunological reactions. Today,
      osseointegration is seen as an immune-modulated inflammatory process where the
      immune system is locally either up- or downregulated. Titanium implant allergy is
      a rare condition, if it exists. The authors found only two papers presenting
      strong evidence of allergy to CP titanium, but with the lack of universally
      accepted and tested patch tests, the precise diagnosis is difficult. CONCLUSIONS:
      CP titanium acts as a foreign body when placed in live tissues. There may be
      immunological reasons behind marginal bone loss. Titanium allergy may exist in
      rare cases, but there is a lack of properly designed and analysed patch tests at
      present.

PMID- 30109299
TI  - A review of the outcome of dental implant provision in individuals with movement
      disorders.
AB  - : Movement disorders encompass a wide range of medical conditions that
      demonstrate changes to muscle function and tone which present with orofacial
      dyskinesia and dystonia. The most common conditions exhibiting these features are
      Parkinson's disease, Down syndrome, chorea and epilepsy. AIM: To establish
      whether implant success in patients suffering from movement disorders is similar
      to the general population, identifying risk factors and noting recommendations
      that may aid maintenance programmes. METHOD: PubMed and Medline searches,
      combined with a manual search of the reference lists of identified full text
      studies. In total, 19 patient case reports and 11 patient case series were
      identified for inclusion in the review. RESULTS: Implant survival in patients may
      be less than expected in patients with movement disorders, but evidence points to
      early rather than late failures. Oral hygiene control was widely reported as an
      issue, although there was insufficient evidence to imply that a lack of oral care
      will cause more rapid deterioration in implant patients with movement disorders.
      Maintenance requirements were low for fixed restorations, but more frequently
      reported in patients treated with overdentures, with the attachment mechanism and
      the prostheses requiring replacement. Chewing and quality of life in relation to
      prosthesis wear were improved. CONCLUSION: Provision of implant-supported
      prostheses improves chewing and quality of life for patients with movement
      disorders and should be considered as an option in the treatment planning for
      tooth loss in this group of patients. However, straightforward designs that lend
      themselves to easier long-term maintenance should be adopted.

PMID- 30109300
TI  - Patients' expectations of oral implants: a systematic review.
AB  - AIM: Nowadays, oral implants are a leading concept in oral rehabilitation.
      Patient satisfaction with this treatment is high, but are the expectations of the
      patients met? The aim of this review was to systematically screen the literature
      on patients' expectations of implant-based therapy before treatment and to assess
      whether these expectations were being met. MATERIALS AND METHODS: A search
      strategy was developed for manuscripts dealing with patients' expectations of
      implant-based therapy to support different types of prosthodontics. Patients had
      an indication for implants, were seeking implants or had received implants.
      PubMed/MEDLINE, Ovid/EMBASE and Cochrane/CENTRAL were searched to identify
      eligible studies. Two reviewers independently assessed the articles. RESULTS: In
      total, 16 out of 3312 studies assessing patients' expectations of patients before
      implant-based therapy matched the inclusion criteria. A variety of methods were
      used in the studies. Patients had high expectations, with function followed by
      aesthetics being the most important expected improvements. Women had higher
      expectations than men. Costs were a major factor against implant-based therapy.
      The expectations that implants will last a lifetime and require no special needs
      of oral hygiene were of concern. CONCLUSION: Prior to treatment, patients have
      high expectations of implant therapy. In general, these expectations are met.
      Most studies revealed that women have higher expectations than men. The variety
      of applied study designs impaired comparability of results. Thus, standardised
      methods for measuring expectations of implant-based therapy are eagerly needed.

PMID- 30109301
TI  - CBCT vs other imaging modalities to assess peri-implant bone and diagnose
      complications: a systematic review.
AB  - AIM: The objective of this systematic review was to evaluate the diagnostic value
      of CBCT compared with 2D imaging and clinical gold standard techniques in peri
      implant bone defect detection and measurement. MATERIALS AND METHODS: Literature
      search was performed using MEDLINE, Embase and Web of Science databases up to
      July 2017. Clinical, ex vivo, in vitro and animal studies that assessed and
      measured peri-implant bone defects using different imaging modalities were
      included in this review. Two reviewers performed data extraction and qualitative
      analysis. The methodological quality of each study was reviewed using the QUADAS
      2 tool. RESULTS: The initial search revealed 2849 unique papers. Full-text
      analysis was performed on 60 articles. For the present review, nine studies were
      considered eligible to be included for qualitative analysis. CBCT performed
      similar to intraoral radiography in mesiodistal defect detection and
      measurements. Additional buccolingual visualisation and volumetric and
      morphological assessment of peri-implant bone defects are major advantages of 3D
      visualisation with CBCT. Nevertheless, one must be aware of metal artefacts
      masking osseointegration, shallow bony defects and other peri-implant
      radiolucencies, thus impeding early diagnosis of intrabony lesions. CONCLUSIONS:
      The present review did not provide evidence to support the use of CBCT as
      standard postoperative procedure to evaluate peri-implant bone. Up to date, we
      are clinically forced to remain with intraoral radiography, notwithstanding the
      inherent limitations related to restricted field of view and two-dimensional
      overlap. A 3D imaging approach for postoperative implant evaluation is crucial,
      making further development of an optimised and artefact-free CBCT protocol
      indispensable.

PMID- 30109302
TI  - Oral implant survival in patients with bisphosphonate (BP)/antiresorptive and
      radiation therapy and their impact on osteonecrosis of the jaws. A systematic
      review.
AB  - AIM: In this systematic review, we aimed to assess the impact of endosseous
      implants on the formation of an osteonecrosis of the jaw, as well as implant
      survival rates for patients under bisphosphonate (BP), antiresorptive and
      radiation therapy. MATERIALS AND METHODS: An electronic search was performed
      using PubMed, Embase, and Medline databases with the logical operators: "dental
      implant", "antiresorptive", "bisphosphonate", "irradiation", "radiotherapy",
      "radiation", "necrosis" and "survival". The search was limited to articles
      published up to 15 December 2016. Recent publications were also searched manually
      to find any relevant studies that might have been missed using the search
      criteria noted above. The outcome variables were the implant survival rate and
      the frequency of osteonecrosis of the jaws. RESULTS: In total, 18 studies
      addressing oral implants in patients with BP or antiresorptive therapy and 23
      with radiation therapy met the inclusion criteria and were included in this
      systematic review. Most of the studies had a retrospective design with a level of
      evidence (LoE) of III (moderately high risk of bias). Implant survival rate
      ranged from 92.86% to 100% in patients with BP/antiresorptive therapy (all due to
      osteoporosis) and 38.5% to 97.9% in patients with radiation therapy. For BP
      patients, osteonecrosis in relation to oral implants more frequently occurred in
      patients taking BPs due to malignant diseases. In patients with radiation
      therapy, an "implant triggered" necrosis is also a potential complication. The
      lack of data in the current literature concerning this issue does not allow a
      proper risk assessment to date. CONCLUSIONS: Within the limits of this systematic
      review, implant treatment concepts seem to be a valuable approach in patients
      with radiation therapy and patients with BP therapy due to an osteoporosis. In
      patients taking BPs due to a malignant disease, implant treatments are not
      recommended due to the high number of reported implant-related necrosis in this
      patient cohort. Outcomes of this review should, however, be regarded with caution
      due to the low level of evidence of the currently existing data.

PMID- 30109303
TI  - Impact of asepsis technique on implant success. A review.
AB  - Asepsis is described as a state free from microorganisms. In medicine, an aseptic
      environment is necessary and expected to avoid the spread of infection through
      contact between persons, sprays and splashes, inhalation, and sharps. Most dental
      procedures are performed in a "clean "environment with the common use of personal
      protective equipment (PPE) such as disposable gloves, masks and protective
      eyewear with disinfection of surfaces and sterilization of instruments. For
      surgical procedure such as the insertion of endosseous implants, the
      recommendations are not clear. The use of antimicrobials and antibiotics before
      and after the procedure remains a controversial issue The purpose of this
      literature review is to evaluate the current evidence as to what is generally
      expected and widely accepted in the use of aseptic techniques for the surgical
      placement of endosseous implants, and the impact on implant survival and overall
      success.

PMID- 30109304
TI  - Long-term clinical outcome of implants with different surface modifications.
AB  - The aim of the present systematic review was to evaluate reported survival rate
      and marginal bone (MBL) loss of implants with different surface roughness and
      followed up for 10 years or longer. For the majority of the 62 included clinical
      studies, no direct comparison between different surfaces was made, thus our
      report is mainly based on reported survival rates and marginal bone loss for
      individual implant brands with known surface roughness. The survival rate was
      82.9 to 100% for all implants after 10 or more years in function and the marginal
      bone loss was, on average, less than 2.0 mm for all implant surfaces included,
      i.e. turned, titanium plasma sprayed (TPS), blasted, anodised, blasted and acid
      etched but the turned surface in general demonstrated the smallest MBL. However,
      the survival rates were in general higher for moderately rough surfaces. The
      roughest TPS surface demonstrated the highest probability for failure, while the
      anodised showed the lowest probability. In conclusion, the present systematic
      review demonstrates that it is possible to achieve very good long-term results
      with all types of included surfaces.

PMID- 30109305
TI  - Extra-short (< 7 mm) and extra-narrow diameter (< 3.5 mm) implants: a meta
      analytic literature review.
AB  - AIM: To review available evidence in scientific literature on oral implants of
      severely reduced length or diameter. MATERIALS AND METHODS: Electronic and hand
      searches up to May 2017 were performed in order to identify clinical
      investigations providing implant survival and/or marginal bone resorption data
      for extra-short implants < 7.0 mm in length and extra-narrow implants < 3.5 mm in
      diameter (excluding one-piece mini-implants). RESULTS: A total of 2929 extra
      short implants and 3048 extra-narrow diameter implants were investigated in 53
      and 29 clinical studies, respectively. Shorter implants between 4.0 mm and 5.4 mm
      in length showed comparable results to implant lengths of 5.5 mm to 6.5 mm (95.1%
      vs. 96.4%, P = 0.121) and no difference regarding marginal bone resorption (0.7
      mm vs 0.5 mm, P = 0.086). Implant lengths of 5.5 mm to 6.5 mm, however, performed
      significantly better in the mandible compared with the maxilla (P = 0.010).
      Smaller diameters between 3.0 mm and 3.25 mm yielded a significantly lower
      survival rate of 94.3% than wider implants of 3.3 mm to 3.4 mm diameter (97.7%, P
      < 0.001), while marginal bone resorption did not differ (0.4 mm vs 0.5 mm, P =
      0.447). CONCLUSIONS: The results of the present literature review suggest that
      extra-short and extra-narrow-diameter implants show satisfactory survival rates
      of around 95% and little marginal bone resorption of around 0.5 mm after a mean
      follow-up of 3 years. However, implant lengths < 7 mm in the maxilla and < 5.5 mm
      in the mandible as well as diameters < 3.3 mm may increase early failure rates.

PMID- 30109306
TI  - Material-related complications in implant-supported fixed dental restorations. A
      systematic review.
AB  - AIM: A large variety of dental materials are available for the production of
      implant-supported fixed restorations. Materials with different properties are
      likely to behave differently during clinical function, which may result in
      different prevalence and types of complications. The aim of the present review
      was to summarise, analyse and discuss the prevalence and types of complications
      or failures related to dental materials in implant-supported restorations.
      MATERIALS AND METHODS: A strategy was set up using the PICO format and the search
      was performed using the PubMed database, including a hand search of reference
      lists. Two independent reviewers selected papers based on a set of criteria. The
      number of events of complications was summarised. RESULTS: The initial search
      produced 2764 titles. After application of criteria, 47 publications were
      selected for analysis. Seventeen studies reported on 1447 single crowns and 30
      studies reported on 2190 fixed dental prostheses. The most common complications
      were fracture or chipping of the veneer material, loss of retention and lost
      access hole fillings. Due to the heterogeneity of studies, and large variation in
      number of restorations per material group, no conclusive correlation between type
      of material and type of technical complication and/or failure could be
      established. CONCLUSIONS: The review did not succeed in providing convincing
      evidence to answer the question concerning a possible relationship between
      restoration materials and prevalence of technical complications in implant
      supported restorations.

PMID- 30109307
TI  - Surgical experience, workload and learning curve vs postoperative outcome.
AB  - AIM: In this review, we look at the factor of the surgical experience and
      surgical workload in a variety of surgical disciplines and its effect on the
      intraoperative and postoperative complications rate. MATERIALS AND METHODS: An
      extensive systematic electronic search was carried out on the relevant databases.
      Two independent reviewers were engaged in selecting appropriate articles in line
      with the protocol. RESULTS: It was very interesting to see that only 52 studies
      could be identified as per the inclusion criteria and search keywords. This
      included studies from 1990 onwards, spanning all surgical disciplines. Six
      studies were identified in third molar surgery, one of the most common surgeries
      practiced across all surgical disciplines. Seven appropriate oral implant surgery
      studies were identified, covering two-stage implants and immediately loaded
      implants. The evidence was overwhelming that the surgeon's experience positively
      correlates with the level of osseointegration and implant success. An interesting
      study from general surgery highlighted the fact it is not unusual to see senior
      surgeons selected to operate on complex patients or carry out complex surgical
      procedures than their junior colleagues. In face, this may explain why a number
      of studies identified no difference in the surgical complications between seniors
      and juniors. CONCLUSIONS: Despite the fact that experience matters, many factors
      can influence the outcome of the surgery. If the surgeon, despite his/her lack of
      seniority, manages to utilise experience appropriately then there will be a
      beneficial outcome for the patient.

PMID- 30109308
TI  - Editorial: Placebo analgesia in dentistry.

PMID- 30109309
TI  - Controversy regarding the need for prophylactic removal of impacted third molars:
      An overview.
AB  - OBJECTIVE: Removal of third molars (3Ms) is one of the most common surgical
      procedures performed by dental surgeons. 3Ms that are associated with pathologic
      changes such as infection, nonrestorable caries lesions, cysts, tumors, and
      destruction of adjacent teeth and bone are under consensus for their removal.
      However, debate exists regarding the prophylactic removal of asymptomatic
      impacted 3Ms. This review attempts to establish indications for prophylactic
      extraction of 3Ms. METHOD AND MATERIALS: Clinical experience and a summary of the
      literature are presented concerning the effects of retained 3Ms in relation to
      caries and periodontal disease, dental arch changes and anterior crowding, cysts
      and other etiologies, mandibular fractures, temporomandibular pain, and aging of
      bone. RESULTS: Nearly half of impacted 3Ms are associated with some form of
      pathology, most frequently caries (20%) and periodontal disease (17%). They
      increase the probability of fractures and their presence results in difficult
      fracture reduction and a higher rate of complication. The number of 3Ms decreases
      rapidly with age, with only 31% remaining at 38 years of age. CONCLUSION:
      Preventive removal of 3Ms at a young age is justified because retained 3Ms are at
      high risk of developing various pathologies. In addition, at older ages
      extraction of 3Ms becomes more complex, with an increased rate of complication
      due to deteriorated systemic physiologic conditions and changes in bone
      physiology.

PMID- 30109311
TI  - Resolving the halogen vs. hydrogen bonding dichotomy in solutions: intermolecular
      complexes of trihalomethanes with halide and pseudohalide anions.
AB  - Halogen- and hydrogen-bonded complexes between trihalomethanes, CHX3, and (pseudo
      )halide anions, A-, co-existing in acetonitrile solutions were identified and
      characterized via a combination of UV-vis and NMR spectral measurements with the
      results of X-ray structural and computational analyses. Halogen-bonded [CHX3, A-]
      complexes displayed strong absorption bands in the UV range (showing Mulliken
      correlations with the frontier orbital energies of the interacting species) and a
      decreased shift of the NMR signal of trihalomethanes' protons. Hydrogen bonding
      led to the opposite (increased) NMR signal shift and the UV-vis absorption bands
      of the hydrogen-bonded [CHX3, A-] complexes were similar in intensity to those of
      the separate CHX3 molecules. The simultaneous multivariable treatment of the
      results of UV-vis and NMR titrations of CHX3 with A- anions afforded formation
      constants of both halogen- and hydrogen-bonded complexes between these species,
      which existed side-by-side in the acetonitrile solutions. The relative values of
      the formation constants were consistent with the magnitudes of the positive
      potentials on the surfaces of the halogen or hydrogen atoms if the effects of the
      polarization of the trihalomethanes due to the presence of the anions were taken
      into account.

PMID- 30109310
TI  - MMP-2-responsive fluorescent nanoprobes for enhanced selectivity of tumor cell
      uptake and imaging.
AB  - It is difficult to develop highly selective substrate-based fluorescent
      nanoprobes for specific matrix metalloproteinases (MMPs) due to overlapping
      substrate specificities among the family of MMP enzymes. To resolve this issue,
      we have developed novel fluorescent nanoprobes that are highly selective for
      soluble MMP-2. Herein, MMP-2-responsive nanoprobes were prepared by immobilizing
      fluorescent fusion proteins on nickel ferrite nanoparticles via the His-tag
      nickel chelation mechanism. The fusion protein consisted of a fluorescent mCherry
      protein with a cell penetrating peptide (CPP) moiety. An MMP-2 cleavage site was
      also introduced within the fusion protein, which was directly linked to the
      nickel ferrite nanoparticles. The selectivity of nanoprobes was modulated by
      hiding the cleavage site of MMP-2 substrates deeply inside the system, which
      could result in strong steric hindrance between the nanoprobes and MMPs,
      especially for membrane-tethered MMPs such as MMP-14. A cell-based assay
      demonstrated that the nanoprobes could only be activated by tumor cells secreting
      soluble MMP-2, but not membrane-tethered MMP-14. To further evaluate the
      contribution of the steric hindrance effect on the nanoprobes, a truncated
      recombinant MMP-14 was employed to confer their cleavage activity as compared to
      native membrane-tethered MMP-14. Furthermore, a designed probe with a diminished
      steric hindrance effect was proved to be activated by membrane-tethered type MMP
      14. The results indicated that the design of fluorescent nanoprobes employing the
      steric hindrance effect can greatly enhance the selectivity of MMP-responsive
      nanoprobes realizing the specific detection of soluble MMP-2 in a tumor
      microenvironment. We believe that highly selective MMP-2-responsive fluorescent
      nanoprobes have broad impacts on biomedical applications including molecular
      imaging and labeling for tumor detection.

PMID- 30109312
TI  - Methanol as a hydrate inhibitor and hydrate activator.
AB  - During their transport to processing plants, produced hydrocarbon streams are
      always accompanied by water appearing as a separate phase in contact with the
      hydrocarbons. Dramatic temperature and pressure changes during processing can
      lead to condensation of water and possibly hazardous formation of ice and
      hydrates. Historically, methanol has been the dominating chemical agent added to
      prevent the formation of solid water phases. In this work, the technique of
      molecular dynamics simulation has been utilized to investigate and illustrate the
      impact of methanol as a surfactant in a water-methane system. We have found that
      adding 5% of methanol boosted the diffusion of methane through the interface by
      more than 40% compared to the reference system. The amount of methane accumulated
      in the aqueous phase was also significantly higher. This effect will likely also
      result in a significant increase in homogeneous and heterogeneous hydrate
      formation in these regions in the case of the methanol-stimulated system, and
      thus necessitate the application of classical nucleation theory. In particular,
      our analysis emphasised the fact that several different hydrates may form in this
      scenario. In case of the homogeneous hydrate formation, there will theoretically
      exist an infinite number of hydrate phases corresponding to concentrations
      spanning the range between methane's solubility and its hydrate stability limit.

PMID- 30109313
TI  - Evolving mechanism of organotemplate-free hierarchical FAU zeolites with house-of
      card-like structures.
AB  - Hierarchical FAU zeolites with house-of-card-like (HCL) structures were
      synthesized through a one-pot organotemplate-free route in the Na2O-Al2O3-SiO2
      H2O system. The structure details and formation mechanism of HCL zeolites were
      determined by the combination of electron crystallography and synthesis
      chemistry. The results revealed that the unique HCL morphology was attributed to
      large solution viscosity, and the evolution process obeyed a skeleton crystal
      growth model due to the limited vortexing effect, which was different from those
      of the HCL zeolites obtained using organic templates.

PMID- 30109314
TI  - Abrupt spin transition in a modified-terpyridine cobalt(ii) complex with a highly
      distorted [CoN6] core.
AB  - The cobalt(ii) complex incorporating pi-conjugated substituent, [Co(Naph-C2
      terpy)2](BF4)2 (1; Naph-C2-terpy = 4'-(2-naphthoxy(ethoxy))-2,2':6',2''
      terpyridine), exhibits an abrupt spin transition (ST) behavior (cooperative
      factor C = 0.91) while its solvated product, 1.2MeOH, shows gradual spin
      crossover (SCO) behavior (C = 0.49). Single crystal X-ray structural analyses
      demonstrated that the octahedral coordination core [CoN6] in 1 shows larger
      distortion in both high-spin and low-spin states than solvated 1.2MeOH or another
      two derivatives, [Co(R-terpy)2](BF4)2 (R = 2-naphthyl (2), 9-anthracenyl (3)).
      The respective distortion parameters (Sigma) are compared with those for
      previously reported SCO cobalt(ii) compounds. The highly-distorted [CoN6] core in
      1 (Sigma = 126 in the HS state and 101.6 in the LS state) was stabilized by
      strong intermolecular interactions and observed an abrupt ST behaviour.

PMID- 30109315
TI  - Thermal-exfoliated synthesis of N-rich carbon-based nanosheets from layered bulk
      crystals of a metal-hexamine framework.
AB  - We develop a general strategy for the design of a series of 2D N-rich carbon
      based nanomaterials through the thermal exfoliation of layered metal-hexamine
      framework microcrystals. By a facile pyrolysis, the sharply generated gases
      escape from the layered precursors, leading to the exfoliation of the layers and
      successful preparation of 2D carbon-based nanomaterials. This strategy can
      readily skip the complicated morphology engineering process of 2D metal-organic
      frameworks to produce 2D N-rich carbon-based nanomaterials on a large scale.

PMID- 30109317
TI  - Solvent effects on the decarboxylation of trichloroacetic acid: insights from ab
      initio molecular dynamics simulations.
AB  - The kinetics of trichloroacetic acid (TCA) decarboxylation strongly depends on
      the solvent in which it occurs, proceeding faster in polar aprotic solvents
      compared to protic solvents. In particular, the reaction is known to be fast in
      DMSO even at room temperature and is rather slow in water even at higher
      temperatures. In order to understand the role of the solvent in the kinetics of
      TCA decarboxylation, the present study investigates this reaction using both ab
      initio molecular dynamics (AIMD) simulations in explicit solvents and static
      electronic structure calculations with the SMD polarizable continuum model,
      considering DMSO and water as solvents. Both methodologies yield activation free
      energies in good agreement with experimental data, however they differ with
      respect to the reaction profile for the process occurring in water. The
      simulations suggest that DMSO does not participate chemically in the reaction and
      that the high reaction rate in DMSO can be explained by differential solvation of
      the reactant and transition state. In water, a protonation step was observed
      along the simulation trajectory, indicating chemical participation of the solvent
      in this case. Moreover, the continuum model has shown to be useful to predict the
      reaction rates in other solvents, suggesting that reaction rates increase upon
      decreasing solvent polarity up to the point where the apolar solvents are not
      able to efficiently screen the strong electrostatic interactions to form the
      required isolated ionic species.

PMID- 30109316
TI  - Interdigitated microelectronic bandage augments hemostasis and clot formation at
      low applied voltage in vitro and in vivo.
AB  - Hemorrhage or uncontrolled bleeding can arise either due to a medical condition
      or from a traumatic injury and are typically controlled with the application of a
      hemostatic agent. Hemostatic agents are currently derived from animal or human
      products, which carry risks of blood borne infections and immune dysregulation.
      Therefore, the need exists for novel biomedical therapies not derived from animal
      or human products to achieve hemostasis. Accordingly, we created an
      interdigitated microelectronic bandage that applies low voltage electrical
      stimulation to an injury site, resulting in faster clot formation without
      excessive heating, accelerated fibrin formation, and hemostasis overall. Our
      interdigitated microelectronic bandage found fibrin formed 1.5* faster in vitro.
      In vivo, total cessation of bleeding was 2.5* faster, resulting in 2* less blood
      loss. Electricity has been used in medical applications such as defibrillation,
      cauterization, and electrosurgery, but scant research has focused on hemostasis.
      Here we report a novel surface treatment using an interdigitated microelectronic
      device that creates rapid hemostasis in both in vitro and in vivo bleeding models
      with low applied voltages, representing a new and novel class of hemostatic
      agents that are electrically-based.

PMID- 30109318
TI  - Block copolymer self-assembly in ionic liquids.
AB  - Ionic liquids (ILs), solely composed of cations and anions, are regarded as a
      novel class of promising liquids, potentially applicable to energy devices,
      reaction media, separation materials, etc. ILs have also attracted great
      attention as new media for molecular self-assembly, capable of producing novel
      soft materials with unique features never observed for conventional soft
      materials containing organic and aqueous solvents. In this review, we focus on
      recent developments in block copolymer (BCP) self-assembly in ILs. Self-assembled
      structures formed by dilute and concentrated BCP solutions in ILs are discussed
      in detail. Ion gels formed by BCP self-assembly have received special interest
      because they exhibit excellent physical properties of tunable viscoelasticity and
      solution processability without impairing the intrinsic properties of ILs, such
      as nonvolatility, nonflammability, and high ionic conductivity. Applications of
      ion gels based on BCP self-assembly for electric double layer capacitors, lithium
      ion batteries, and electroactive soft actuators are also addressed.

PMID- 30109319
TI  - Design and synthesis of tailored human caseinolytic protease P inhibitors.
AB  - Human caseinolytic protease P (hClpP) is important for degradation of misfolded
      proteins in the mitochondrial unfolded protein response. We here introduce
      tailored hClpP inhibitors that utilize a steric discrimination in their core
      naphthofuran scaffold to selectively address the human enzyme. This novel
      inhibitor generation exhibited superior activity compared to previously
      introduced beta-lactones, optimized for bacterial ClpP. Further insights into the
      bioactivity and binding to cellular targets were obtained via chemical proteomics
      as well as proliferation- and migration studies in cancer cells.

PMID- 30109320
TI  - A supramolecular hybrid material constructed from pillar[6]arene-based host-guest
      complexation and ZIF-8 for targeted drug delivery.
AB  - A novel supramolecular hybrid material ZIF-8@DOX@WP6@G constructed from the host
      guest complexation between carboxylated pillar[6]arene (WP6) and a galactose
      derivative (G), and doxorubicin (DOX)-loaded ZIF-8 has been synthesized for
      targeted drug delivery. The results showed that ZIF-8@DOX@WP6@G not only
      maintained the pH-sensitive drug release properties of ZIF-8 but also exhibited
      excellent water dispersibility and selective toxicity for hepatoma cancer cells
      due to the assembly of WP6 and G. The strategy used in this study opens up a new
      avenue for constructing multifunctional supramolecular hybrid materials for
      therapeutic applications in cancer treatment.

PMID- 30109321
TI  - Trends in the valence band electronic structures of mixed uranium oxides.
AB  - The valence band electronic structures of mixed uranium oxides (UO2, U4O9, U3O7,
      U3O8, and beta-UO3) have been studied using the resonant inelastic X-ray
      scattering (RIXS) technique at the U M5 edge and computational methods. We show
      here that the RIXS technique and recorded U 5f-O 2p charge transfer excitations
      can be used to test the validity of theoretical approximations.

PMID- 30109322
TI  - Native defects and impurity band behavior in half-Heusler thermoelectric NbFeSb.
AB  - To investigate the electronic behavior and magnetic properties of NbFeSb, we have
      performed 93Nb NMR, specific heat and magnetic measurements on NbFeSb samples
      heat treated at high temperatures. Magnetic measurements combined with an
      observed Schottky anomaly and changes in the NMR line width indicate the presence
      of a 0.2% concentrated native magnetic defect in stoichiometric NbFeSb samples.
      The origin of these native defects is believed to be due to Fe antisites on Nb
      sites. In addition, NMR shift and spin-lattice relaxation results below 200 K
      reveal a Korringa-like response indicating heavily-doped p-type behavior due to
      native defects. Above 280 K, this converts to an activated behavior, indicating
      the presence of an impurity band, empty at low temperatures, which is located
      around 0.03 eV above the valence band maximum.

PMID- 30109326
TI  - Highly efficient fluorescence sensing of phosphate by dual-emissive lanthanide
      MOFs.
AB  - The detection of phosphate (Pi) under physiological conditions is a very
      important issue in environmental and biological sciences. Herein, a unique
      fluorescent probe {[EuL(H2O)1.35(DMF)0.65].1.9DMF}n (1) was prepared through the
      organic-inorganic hybridization between asymmetrical tricarboxylate ligands and
      Eu2O2 clusters under solvothermal conditions. The as-prepared sample 1 exhibited
      excellent fluorescence properties and could be designed as a self-calibrating
      fluorescent probe for sensitively and selectively detecting Pi which served as an
      essential substance in aquatic ecosystems and biological systems. The different
      responses of the two emission peaks caused by the addition of Pi resulted in a
      continuous fluorescence color change, which could be clearly observed with the
      naked eye under UV light lamp illumination at 302 nm. Typically, a good linearity
      existed between the ratio of dual fluorescence intensities and the Pi contents
      ranging from 0.1 MUM to 15 MUM with a low detection limit of 52 nM (S/N = 3). It
      is noteworthy that the prepared self-calibrating fluorescent probe displayed
      specific recognition towards Pi anions with satisfactory recovery ranging from
      92.8% to 100.6% in water samples and biological fluids. Thus, we can envision
      that this work may open a new avenue for the detection of many other bioactive
      ions in environmental and biological samples.

PMID- 30109325
TI  - The influence of ortho-methyl substitution in organometallic self-assembly - a
      comparative study on Cu(111) vs. Ag(111).
AB  - Metal surface-induced dehalogenation of precursors is known to initiate self
      assembly of organometallic networks, where tectons are connected via carbon-metal
      carbon (C-M-C) bonds. Even though reversibility of the C-M-C bonds facilitates
      structural equilibration, defects associated with highly bent organometallic
      linkages are still commonly observed. By introducing a steric hindrance to reduce
      the C-M-C bond angle flexibility, we find well ordered organometallic networks of
      an ortho-methyl substituted 1,3,5-tris(p-bromophenyl)benzene analogue on Cu(111)
      after room-temperature (RT) deposition and on Ag(111) after annealing.

PMID- 30109327
TI  - Integrated production of bio-jet fuel containing lignin-derived arenes via lipid
      deoxygenation.
AB  - We report an integrated production of bio-jet fuel, from dehydrogenation of
      lignin-derived cycloalkanes and deoxygenation of lipid over PtIr/gamma-Al2O3 at
      400  degrees C in the absence of hydrogen. The CO generated in situ via lipid
      decarbonylation is strongly adsorbed by Ir and subsequently undergoes
      methanation, with the remaining Pt sites catalyzing cycloalkane dehydrogenation.

PMID- 30109328
TI  - Photochemical activation of SF6 by N-heterocyclic carbenes to provide a
      deoxyfluorinating reagent.
AB  - The activation of the greenhouse gas SF6 using electron-rich N-heterocyclic
      carbenes gave 2,2-difluoroimidazolines or 2,2-difluoroimidazolidines as well as 2
      thio derivatives of the carbene precursors. The N-heterocyclic carbenes can also
      convert SF4 to give similar products. The difluoroimidazolidine derivatives were
      applied in deoxyfluorination reactions. Furthermore, the activation of SF6 and
      the fluorination can be coupled in a one-pot process to convert 1-octanol into 1
      fluorooctane.

PMID- 30109330
TI  - Optimizing edges and defects of supported MoS2 catalysts for hydrogen evolution
      via an external electric field.
AB  - As a fascinating non-precious catalyst for hydrogen evolution reaction (HER), two
      dimensional (2D) molybdenum disulphide (MoS2) has attracted ever-growing
      interest. While the pristine basal plane of MoS2 is chemically inactive, certain
      edges and defects have been recognized to be catalytically active for HER.
      Nevertheless, the per-site activity of MoS2 is still much lower than that of Pt.
      Therefore, further optimization of active sites becomes highly desirable to
      enhance the overall catalytic activity of MoS2. In this work, we propose to use
      an electric field to engineer the electronic structure of edges and defects of
      MoS2, aiming to optimize its catalytic performance. Via systematic density
      functional theory based first-principles calculations, we investigated the
      adsorption of H atoms on different edges of free-standing and supported MoS2,
      revealing the critical role of S p-resonance states near the Fermi level in
      determining H adsorption, which offers an excellent descriptor for the catalytic
      activity associated with the electronic structure. Remarkably, by introducing an
      external electric field, we demonstrate the ability to fine tune the position of
      S p-resonance states, which can give an optimal H adsorption strength on MoS2 for
      HER. We also explored field effects on S vacancies in the basal plane, which show
      a different behavior for H adsorption due to the presence of Mo d states that are
      insensitive to the electric field. We expect these findings to shed new light on
      the design and control of MoS2-based catalysts for industrial applications.

PMID- 30109329
TI  - Microfluidic-enabled quantitative measurements of insulin release dynamics from
      single islets of Langerhans in response to 5-palmitic acid hydroxy stearic acid.
AB  - Proper release of insulin from pancreatic islets of Langerhans is essential for
      maintaining glucose homeostasis. For full efficacy, both the pattern and the
      amount of hormone release are critical. It is therefore important to understand
      how insulin levels are secreted from single islets in both a quantitative fashion
      and in a manner that resolves temporal dynamics. In this study, we describe a
      microfluidic analytical system that can both quantitatively monitor insulin
      secretion from single islets while simultaneously maintaining high temporal
      sampling to resolve dynamics of release. We have applied this system to determine
      the acute and chronic effects of a recently-identified lipid, 5-palmitic acid
      hydroxy stearic acid (5-PAHSA), which is a member of the fatty acid hydroxy fatty
      acid class of lipids that are upregulated in healthy individuals. Chronic
      incubation (48 h) with 5-PAHSA significantly increased glucose-stimulated insulin
      secretion (GSIS) in murine islets compared to chronic incubation without the
      lipid or in the presence of palmitic acid (PA). The studies were continued in
      human islets from both healthy donors and donors diagnosed with type 2 diabetes
      mellitus (T2DM). Total amounts of GSIS were not only augmented in islets that
      were chronically incubated with 5-PAHSA, but the dynamic insulin release profiles
      also improved as noted by more pronounced insulin oscillations. With this
      quantitative microfluidic system, we have corroborated the anti-diabetic effects
      of 5-PAHSA by demonstrating improved islet function after chronic incubation with
      this lipid via improved oscillatory dynamics along with higher basal and peak
      release rates.

PMID- 30109332
TI  - Fluorescence behaviour of 2-, 3- and 4-amino-1,8-naphthalimides: effects of the
      substitution positions of the amino functionality on the photophysical
      properties.
AB  - The absorption and fluorescence spectra of a series of 1,8-naphthalimide
      derivatives incorporating the amino functionality at the 2-, 3- and 4-positions
      of the naphthalene ring (2APNI, 3APNI and 4APNI, respectively) were
      systematically investigated in various solvents and in the solid state. The
      fluorescence spectra of 2APNI were insensitive to solvent polarity and
      intermolecular hydrogen-bonding even in a protic medium such as methanol. Thus,
      2APNI displayed blue fluorescence with a moderate fluorescence quantum yield
      (lambdaFmax = 420-445 nm, PhiF 0.2-0.3) in the solvents investigated. In
      contrast, the fluorescence spectra of 3APNI and 4APNI were strongly solvent
      dependent showing positive solvatofluorochromism with large Stokes shifts. Upon
      increasing the solvent polarity, the fluorescence colours changed from blue in
      hexane (lambdaFmax = 429 nm) to orange-yellow in methanol (lambdaFmax = 564 nm)
      for 3APNI, and from blue in hexane (lambdaFmax = 460 nm) to yellow in methanol
      (lambdaFmax = 538 nm) for 4APNI. The fluorescence quantum yields of 3APNI and
      4APNI decreased with increasing solvent polarity. In the solid state, APNIs
      displayed red-shifted fluorescence emission compared to that in solution
      (lambdaFmax = 541 nm for 2APNI, 575 nm for 3APNI, and 561 nm for 4APNI) and the
      fluorescence quantum yields in the solid state were lower than those in solution.

PMID- 30109333
TI  - Functionalization of diazotetronic acid and application in a stereoselective
      modular synthesis of pulvinone, aspulvinones A-E, G, Q and their analogues.
AB  - A modular synthesis of aspulvinones A, B, C, D, E, G and the recently isolated
      aspulvinone Q was developed. The methodology features a highly stereoselective
      aldol condensation of diazotetronic acid with aldehydes to provide 5-arylidene
      diazotetronates. Subsequent catalytic intermolecular C-H insertion reactions of
      the arylidene tetronates with arenes provide a series of naturally occurring
      aspulvinones including aspulvinones C, D and Q which have not been synthesized
      before. Variation of the aldehyde and the arene components furnishes synthetic
      analogues of the aspulvinones.

PMID- 30109334
TI  - One-step fabrication of bimetallic PtNi mesoporous nanospheres as an efficient
      catalyst for the oxygen reduction reaction.
AB  - The controlled synthesis of Pt-based bimetallic porous nanostructures is highly
      important for the design of electrocatalysts with high performance. Herein, we
      report a one-step method for the direct synthesis of well-dispersed bimetallic
      PtNi mesoporous nanospheres (PtNi MNs) at high yield. Benefitting from the
      synergistic effect of composition (bimetallic PtNi) and structure (mesoporous and
      highly open structure), the as-obtained PtNi MNs exhibit superior catalytic
      activity and stability for the oxygen reduction reaction.

PMID- 30109335
TI  - Stretchable thin-film transistors with molybdenum disulfide channels and graphene
      electrodes.
AB  - Two-dimensional (2D) materials including graphene and transition metal
      dichalcogenides (TMDCs) have attracted great interest as new electronic
      materials, given their superior properties such as optical transparency,
      mechanical flexibility, and stretchability, especially for application in next
      generation displays. In particular, the integration of graphene and TMDCs enables
      the implementation of 2D materials-based thin-film transistors (TFTs) in
      stretchable displays, given that TFTs are the fundamental element of various
      modern devices. In the present study, we demonstrate chemical-vapor-deposited
      molybdenum disulfide and graphene-based TFTs on a polymer substrate and
      investigate the electrical characteristics of TFTs under mechanical deformation
      to determine the stretchability of our devices. Furthermore, the mechanisms
      leading to TFT performance degradation are investigated, as they relate to the
      change in the contact resistance that is closely associated with the relative
      deformation of 2D materials under mechanical stress. Therefore, the synergetic
      integration of 2D materials with versatile electrical properties provides an
      important strategy for creating 2D materials-based stretchable TFTs, thus
      extending the excellent potential of 2D materials as innovative materials for
      stretchable active-matrix displays.

PMID- 30109336
TI  - Phosphite-catalyzed alkoxycarbonylation of aryl diazonium salts.
AB  - In this communication, an interesting phosphite-catalyzed alkoxycarbonylation of
      aryl diazonium salts has been reported. At room temperature and under CO
      pressure, moderate to good yields of the desired esters can be produced in the
      absence of bases or any other additives.

PMID- 30109337
TI  - Elucidation of the catalytic mechanism of 6-hydroxymethyl-7,8-dihydropterin
      pyrophosphokinase using QM/MM calculations.
AB  - The folate pathway is a recognized intervention point for treating parasitic and
      bacterial infections in humans. However, the efficacy of treatments targeting
      dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) has reduced
      due to disease-related mutations. This has prompted interest in other enzyme
      targets on this clinically validated pathway, including 6-hydroxymethyl-7,8
      dihydropterin pyrophosphokinase (HPPK). A challenge in the design of molecules to
      target this enzyme is that the precise mechanism of the reaction and the role of
      the active site residues are not fully understood. In this study, we report the
      first theoretical analysis of the catalytic pathway of the natural substrate
      using hybrid quantum mechanical/molecular mechanical (QM/MM) methods. The
      reaction profiles associated with three proposed general bases have been
      investigated, as well as the profile for two mutant enzymes, namely R92A and
      R82A. We identified R92 as the general base in the wildtype reaction. The
      predicted barriers are in good agreement with the observed experimental kcat
      values obtained for wildtype and mutant proteins.

PMID- 30109338
TI  - Surfactant controlled zwitterionic cellulose nanofibril dispersions.
AB  - Zwitterionic cellulose nanofibrils (ZCNFs) with an isoelectric point of 3.4 were
      obtained by grafting glycidyltrimethylammonium chloride onto TEMPO/NaBr/NaOCl
      oxidised cellulose nanofibrils. The ZCNF aqueous dispersions were characterized
      via transmission electron microscopy, rheology and small angle neutron
      scattering, revealing a fibril-bundle structure with pronounced aggregation at pH
      7. Surfactants were successfully employed to tune the stability of the ZCNF
      dispersions. Upon addition of the anionic surfactant, sodium dodecyl sulfate, the
      ZCNF dispersion shows individualized fibrils due to electrostatic stabilization.
      In contrast, upon addition of the cationic species dodecyltrimethylammonium
      bromide, the dispersion undergoes charge neutralization, leading to more
      pronounced flocculation.

PMID- 30109339
TI  - Bending nematic liquid crystal membranes with phospholipids.
AB  - The interactions of phospholipids with liquid crystals have formed the basis for
      attractive biosensor technologies, but many questions remain concerning the basic
      physics and chemistry of these interactions. Phospholipids such as 1,2-dilauroyl
      sn-glycero-3-phosphocholine (DLPC), at sufficiently high (~1 MUM) concentrations
      and/or sufficiently long times, turn the liquid crystal director perpendicular to
      the LC/water interface. If the other side of the LC film is in contact with a
      surface that prefers perpendicular alignment, the LC film appears completely dark
      between crossed polarizers. Recently, however, Popov et al. (J. Mater. Chem. B,
      2017, 5, 5061) noted that at even higher (~10 MUM) DLPC concentrations, the
      liquid crystal texture brightens again between crossed polarizers. To explain
      this surprising observation, it was suggested that the LC interface might bend.
      In this paper we show by optical surface profiler measurements that indeed the
      interface of the LC film of 4-cyano-4'-octylbiphenyl (8CB) suspended in a
      transmission electron microscopy (TEM) grid with openings of ~0.5 mm in diameter
      bends towards the lipid-coated interface. We demonstrate that where the bending
      occurs, the bent interface exhibits extreme sensitivity to air pressure
      variations, producing an optical response with acoustic stimulation. Finally, we
      suggest a physical mechanism for this astonishing result.

PMID- 30109340
TI  - Material gradients in fibrillar insect attachment systems: the role of joint-like
      elements.
AB  - Insects have developed elaborate fibrillar (or hairy) attachment systems that
      allow them to attach reliably on a variety of different and unpredictable
      surfaces. These hairy adhesive pads consist of fine and long surface outgrowths
      (setae), terminated by thin plate-like tips of different shapes. Besides
      structural adaptations, recent work revealed material gradients along the length
      of the setae with spatula-shaped and pointed tip structures. It was shown that
      these setae have a rigid base and soft setal tips, which is assumed to enhance
      the adaptability to rough surfaces and prevent clustering of the setae. Here, we
      show a not yet described type of material gradient found in discoidal (or
      mushroom-shaped) setae of male leaf beetles. In contrast to the previously shown
      gradient, the setal tips and the basal and central seta sections are composed of
      relatively stiff chitinous materials, whereas the transition zones between the
      central seta sections and the setal tips contain large proportions of the rather
      soft and elastic protein resilin, forming a joint-like element. Having performed
      adhesion measurements with artificial macroscopic mushroom-shaped adhesive
      structures with different implemented joint-like elements, we show that the main
      functional role of these joint-like elements is to facilitate the adaptability to
      uneven and non-parallel substrates, rather than to provide detachment tolerance
      towards pull-off forces applied under various tilt angles.

PMID- 30109341
TI  - Salt-dependent properties of a coacervate-like, self-assembled DNA liquid.
AB  - Liquid-liquid phase separation of a polymer-rich phase from a polymer-dilute
      solution, known generally as coacervation, has been observed in a variety of
      biomolecular systems. Understanding of this process, and the properties of the
      resulting liquid, has been hampered in typical systems by the complexity of the
      components and of the intermolecular interactions. Here, we examine a single
      component system comprised entirely of DNA, in which tetravalent DNA nanostar
      particles condense into liquids through attractive bonds formed from basepairing
      interactions. We measure the density, viscosity, particle self-diffusion, and
      surface tension of NS-liquid droplets. The sequence- and salt-dependent
      thermodynamics of basepairing accounts for most properties, particularly
      indicating that particle transport is an activated process whose barrier is the
      breaking of a single bond, and that very few bonds are broken at the surface.
      However, more complex effects are also seen. The relation of density to salt
      shows that electrostatic screening compacts the NS particles. Further, the
      interrelation of the transport properties indicates a breakdown of the Stokes
      Einstein relation. This observation, in concert with the low surface tension and
      single-bond transport barrier, suggests this DNA liquid has a heterogeneous,
      clustered structure that is likely enabled by internal NS particle flexibility.
      We discuss these results in comparison to other coacervate systems.

PMID- 30109343
TI  - 3-D manipulation of a single nano-droplet on graphene with an electrowetting
      driving scheme: critical condition and tunability.
AB  - The next generation of micro/nano-fluidic systems, featuring manipulation of a
      single nanoliter volume of a chemical reactant or bio-substance, is greatly
      dependent on the accurate manipulation of a single nano-droplet. In this paper,
      to resolve the lack of efficient methods for 3-D actuation of nano-droplets with
      high tunability, we proposed an electro-wetting-on-dielectric (EWOD) driving
      scheme on a graphene surface. The droplet could be actuated when the EWOD
      saturated contact angle was reached, which determined the critical magnitude of
      the E-field. The droplet velocity agreed well with the vcom ~ E1/2C-O law due to
      the film-detachment mechanism, which indicated the low viscous dissipation and
      good tunability of the proposed technique. The droplet velocity could also be
      tuned by changing the initial wettability of the graphene surface. Detailed
      examination of the liquid-solid interface revealed significant penetration of
      water molecules into the inner Helmholtz plane (IHP) before the induction of
      droplet detachment when the electric energy was converted into surface energy.
      For all the studied cases, the saturated contact angle served as a sufficient
      condition for the actuation of droplets.

PMID- 30109344
TI  - Band offsets in new BN/BX (X = P, As, Sb) lateral heterostructures based on bond
      orbital theory.
AB  - Identifying heterostructures with tunable band alignments remains a difficult
      challenge. Here, based on bond-orbital theory, we propose a series of new BN/BX
      (X = P, As, Sb) lateral heterostructures (LHS). Our first principles calculations
      reveal that the LHS interlines have a substantial impact on the electronic
      properties. Importantly, we start with the chemical concepts, such as bond length
      and strength as well as orbital overlap interaction, in an attempt to thoroughly
      investigate the electronic properties, namely the band offset, the band gap (Eg)
      and the state of the energy level. We demonstrate that the newly designed BN/BX
      LHS have profound implications for developing advanced optoelectronics, such as
      high-performance light-emitting diodes and lasers. Furthermore, the new BN/BX LHS
      designed from the chemical viewpoint can shed new light on overcoming the
      enormous hurdle of ineffective and laborious material design.

PMID- 30109345
TI  - Recent developments in functionalization of acyclic alpha-keto amides.
AB  - alpha-Keto amides are a key frame in biology, medicinal chemistry and synthetic
      chemistry as drug molecules and key intermediates. Based on the structural
      aspect, an acyclic alpha-keto amide has multiple reactive centres which have
      electrophilic and nucleophilic characters. In this review, we focus on the recent
      developments of both asymmetric and achiral reactions involving acyclic alpha
      keto amides as the reactants for the synthesis of cyclic and acyclic molecules
      through the formation of C-C, C-O, C-N and C-H bonds. Based on the reactivity of
      alpha-keto amides, this article is divided into three major classes: 1. mono
      functionalization, 2. dual functionalization, and 3. triple functionalization of
      alpha-keto amides, which are further divided into sub-classes as well. Over 50
      examples including our own work have been demonstrated for the functionalization
      of acyclic alpha-keto amides since 1992. Moreover, the usefulness of alpha-keto
      amides is shown for the synthesis of biologically active molecules, synthetic
      intermediates, heterocycles, valuable compounds, building blocks and metal
      complexes.

PMID- 30109346
TI  - Synthesis of next generation dual-responsive cross-linked nanoparticles and their
      application to anti-cancer drug delivery.
AB  - Rare earth metal-mediated group transfer polymerisation enables the synthesis of
      previously inaccessible block copolymers of 2-vinylpyridine, diethyl
      vinylphosphonate and the new diallyl vinylphosphonate monomer. This precision
      polymerisation and the selective cross-linking of allyl side groups via thiol-ene
      click chemistry leads to the formation of well-defined dual-responsive
      nanoparticles. We demonstrate that these next generation nanocarriers are pH- and
      temperature-responsive and are capable of efficiently delivering doxorubicin into
      the nucleus of cancer cells. High anti-cancer activity could be demonstrated via
      cytotoxicity tests on breast cancer (MCF-7) and cervical cancer (HeLa) cells.
      These results validate this modular synthesis route as an ideal platform for the
      development of sophisticated nanocarriers for future drug delivery applications.

PMID- 30109347
TI  - Some activities of PorphyChem illustrated by the applications of porphyrinoids in
      PDT, PIT and PDI.
AB  - Photodynamic therapy is an innovative approach to treat diverse cancers and
      diseases that involves the use of photosensitizing agents along with light of an
      appropriate wavelength to generate cytotoxic reactive oxygen species. Among the
      collection of potential dye candidates, porphyrinoids (i.e. porphyrins, chlorins,
      and phthalocyanines) are probably the most promising photosensitizers for PDT
      applications. This review shows the great potential of these derivatives for
      their industrial development in the field of health through different
      applications in photodynamic therapy (PDT), photoimmunotherapy (PIT),
      ophthalmology, dermatology and photodynamic inactivation (PDI). The purpose of
      this survey is also to show the new trends and evolutions in these fields.

PMID- 30109348
TI  - Increase in impact factor for the SMJ.

PMID- 30109349
TI  - High-grade atrioventricular block.
AB  - Atrioventricular (AV) block is an AV conduction disorder that can manifest in
      various settings, with varying symptomaticity and severity. The electrocardiogram
      is a key diagnostic tool for management, and careful interpretation is necessary
      to institute the correct management. We described two cases of patients with
      bradycardia due to AV blocks and discussed the electrocardiogram interpretation
      and management.

PMID- 30109351
TI  - Associate Professor Khim Nian Sin Fai Lam (1949-2018).

PMID- 30109350
TI  - Extreme exigency in the extremity: an illustrative case of diffuse large B-cell
      lymphoma occurring in the arm.

PMID- 30109352
TI  - Virginia Apgar (1909-1974): Apgar score innovator.

PMID- 30109353
TI  - Clinics in diagnostic imaging (188). Transient global amnesia (TGA).
AB  - A 60-year-old woman was travelling on a plane with her spouse when she suddenly
      developed acute-onset disorientation to time and space. According to her husband,
      she repetitively questioned her whereabouts and complained of a minor headache.
      Upon landing, she was immediately brought to the emergency room and subsequent
      magnetic resonance imaging was performed, which showed multiple punctate 2-3 mm
      regions of diffusion-weighted imaging hyperintensity in the medial aspects of
      both temporal lobes. The conglomeration of clinical history and radiological
      findings was most suggestive of transient global amnesia. This article discussed
      the background, proposed mechanisms, diagnosis, radiological characteristics and
      management of transient global amnesia.

PMID- 30109354
TI  - Isolated thrombocytopenia in childhood: what if it is not immune
      thrombocytopenia?
AB  - INTRODUCTION: Childhood immune thrombocytopenia (ITP) remains a diagnosis of
      exclusion when isolated thrombocytopenia is not part of another disease process.
      In practice, the diagnosis of ITP can only be confirmed when thrombocytopenia
      resolves or is excluded after the recognition of a primary cause. METHODS: The
      records of 87 consecutive children with isolated thrombocytopenia seen over a
      nine-year period in a private paediatric haematology practice were reviewed
      retrospectively. Children in whom a primary cause was eventually found were the
      subjects of a further descriptive study. RESULTS: 9 (10%) children with isolated
      thrombocytopenia were not diagnosed with ITP because a primary disease was found.
      Of these nine cases, four had thrombocytopenia recognised during the neonatal
      period, consisting of perinatal cytomegalovirus infection (n = 2), meconium
      aspiration pneumonia (n = 1) and transient abnormal myelopoiesis associated with
      Down syndrome (n = 1). The remaining five children were each found to have
      familial thrombocytopenia, portal hypertension, cutaneous mastocytosis, May
      Hegglin anomaly and systemic lupus erythematosus. Two of them had a history of
      failure of response to corticosteroid therapy. CONCLUSION: Secondary
      thrombocytopenia is not uncommon in a tertiary paediatric specialty practice with
      adequate evaluation. Thrombocytopenia occurring during the newborn period and
      failure of steroid therapy are predictive of secondary cases.

PMID- 30109355
TI  - Comparison of outcomes following laparoscopic and open hysterectomy with pelvic
      lymphadenectomy for early stage endometrial carcinoma.
AB  - INTRODUCTION: Endometrial carcinoma is the most common gynaecological malignancy.
      Studies have shown that laparoscopic total hysterectomy, bilateral salpingo
      oophorectomy and pelvic lymph node dissection was advantageous compared to
      laparotomy in reducing length of stay and intraoperative blood loss. However,
      these studies had a predominantly Caucasian population. A comparison study was
      conducted among the Singapore population to investigate the differences in
      oncological and surgical outcomes between these two methods. METHODS: A
      retrospective, single-centre cohort study was conducted. Records of hospitalised
      patients with Stage 1 endometrioid carcinoma from 2008 to 2014 were extracted for
      review. Demographic data and study-specific parameters, including operative time,
      length of hospitalisation, intraoperative and postoperative complications, pain
      scores, final staging and recurrence rates, were compared between the two groups.
      RESULTS: 475 endometrioid carcinoma patients were admitted for surgical staging,
      among whom 374 fulfilled our inclusion criteria. Out of these patients, 229
      underwent laparotomy and 145 underwent laparoscopy. The race, parity and body
      mass index of both groups were comparable. Patients who underwent laparoscopic
      surgery reported reduced pain score within two hours postoperatively (p = 0.007)
      and at Postoperative Days 1, 2 and 3 (p < 0.001). Laparoscopic surgery also
      illustrated better outcomes such as reduced length of stay (p < 0.001) and
      reduced intraoperative blood loss (p < 0.001). The operative time, recurrence
      rate and disease-free intervals were comparable between both groups. CONCLUSION:
      Laparoscopy offered similar oncological outcomes with superior surgical outcomes
      compared to laparotomy. It provides a suitable alternative in the surgical
      staging of endometrioid carcinoma.

PMID- 30109358
TI  - [What is Practical in Mathematical Knowledge? : The Positions of Mining Master J.
      A. Scheidhauer and Building Master C. F. Steiner Around 1800].
AB  - This article investigates the notion of 'practical mathematics' and its evolution
      over the last third of the eighteenth and first third of the nineteenth century.
      Two detailed case studies, taken together, give a sense of both the richness and
      the difficulties of what practical knowledge could mean at the turn of the
      nineteenth century. After some preliminary remarks about the institutional
      context and the social status of practical mathematicians (actually mathematical
      practitioners) in the German regions the first case study is dedicated to the
      mining master Johann Andreas Scheidhauer (1718-1784). The biography of this
      previously unknown mathematical practitioner leads to an analysis of his writings
      and their reception, after which we analyze the diffusion of his work, most
      prominently through J. F. Lempe, professor of mathematics at the Freiberg mining
      academy. The second case study deals with a practitioner from the following
      generation: the architect Carl Friedrich Steiner (1774-1840), who lived in Weimar
      as a contemporary of Goethe. In a certain sense his textbook on Geometry
      descriptive reflects the consequences of the ongoing mathematisation, the status
      of mathematical knowledge for the training of young artisans and artists. Both
      case studies provide information about the historical understanding of practical
      mathematics.

PMID- 30109359
TI  - [Avascular femoral head necrosis].

PMID- 30109356
TI  - Quetiapine ameliorates collagen-induced arthritis in mice via the suppression of
      the AKT and ERK signaling pathways.
AB  - OBJECTIVE AND DESIGN: To investigate the amelioration effects of quetiapine on
      rheumatoid arthritis with RAW 264.7 macrophage and collagen-induced arthritis
      (CIA) DBA/1J mouse model. SUBJECTS: RAW 264.7 macrophage and DBA/1J mice.
      TREATMENT: Lipopolysaccharide and collagen. METHODS: RAW 264.7 macrophages
      stimulated by lipopolysaccharide (LPS) followed by quetiapine treatments were
      investigated. Activations of CD80 and CD86 were analyzed by flow cytometry. Pro
      inflammatory cytokines such as IL-6, TNF-alpha and IL-1beta were analyzed by
      ELISA. Proteins involved in signaling pathways related to the formation of
      rheumatoid arthritis were assayed by Western blotting. Therapeutic efficacy of
      quetiapine in CIA mouse model was also assayed. 18F-FDG/micro-PET was used to
      monitor the inflammation status in the joints, and the severity of bone erosion
      was evaluated with micro-CT and H&E staining. RESULTS: The inhibition of pro
      inflammatory cytokines by quetiapine was found through the ERK and AKT
      phosphorylation and subsequent NF-kappaB and CREB signaling pathways. Pro
      inflammatory cytokines such as IL-17, IL-6 and IL-1beta were decreased, while
      immunosuppressive factors such as TGF-beta and IL-10 were increased in CIA mice
      treated with quetiapine. Notably, no uptake of 18F-FDG and bone erosion was found
      with micro-PET images on days 32 and 43 in the quetiapine-treated and normal
      control groups. However, significant uptake of 18F-FDG could be observed in the
      CIA group during the same time course. Similar results were further verified with
      ex vivo autoradiography. CONCLUSION: Taken together, these results suggest that
      quetiapine is a potential anti-inflammatory drug, and may be used as an adjuvant
      for the treatment of rheumatoid arthritis.

PMID- 30109357
TI  - PHAB toxins: a unique family of predatory sea anemone toxins evolving via intra
      gene concerted evolution defines a new peptide fold.
AB  - Sea anemone venoms have long been recognized as a rich source of peptides with
      interesting pharmacological and structural properties, but they still contain
      many uncharacterized bioactive compounds. Here we report the discovery, three
      dimensional structure, activity, tissue localization, and putative function of a
      novel sea anemone peptide toxin that constitutes a new, sixth type of voltage
      gated potassium channel (KV) toxin from sea anemones. Comprised of just 17
      residues, kappa-actitoxin-Ate1a (Ate1a) is the shortest sea anemone toxin
      reported to date, and it adopts a novel three-dimensional structure that we have
      named the Proline-Hinged Asymmetric beta-hairpin (PHAB) fold. Mass spectrometry
      imaging and bioassays suggest that Ate1a serves a primarily predatory function by
      immobilising prey, and we show this is achieved through inhibition of Shaker-type
      KV channels. Ate1a is encoded as a multi-domain precursor protein that yields
      multiple identical mature peptides, which likely evolved by multiple domain
      duplication events in an actinioidean ancestor. Despite this ancient evolutionary
      history, the PHAB-encoding gene family exhibits remarkable sequence conservation
      in the mature peptide domains. We demonstrate that this conservation is likely
      due to intra-gene concerted evolution, which has to our knowledge not previously
      been reported for toxin genes. We propose that the concerted evolution of toxin
      domains provides a hitherto unrecognised way to circumvent the effects of the
      costly evolutionary arms race considered to drive toxin gene evolution by
      ensuring efficient secretion of ecologically important predatory toxins.

PMID- 30109360
TI  - [Palliative care].
AB  - Improvement in the quality of life of patients with life-threatening illnesses or
      incurable progressive diseases, including patients with cancer and also several
      internal medical diseases, represents the major aim of palliative care. Basic
      principles are to also address the needs of the family caregiver and a
      comprehensive understanding of physical symptoms and psychosocial as well as
      spiritual aspects. Treatment planning for physical symptoms, e.g., pain, dyspnea
      and nausea, in patients in need of palliative care has to include the subjective
      symptom distress of the patient, factors that can be treated causally and the
      treatment limitations resulting from the underlying life-threatening or incurable
      disease. During terminal care all treatment measures should only focus on relief
      of symptom burden and fulfilling the patient's will.

PMID- 30109362
TI  - [Erratum to: Ethics, evidence and electroconvulsive therapy].

PMID- 30109361
TI  - Unilateral cochlea sparing in locoregionally advanced head and neck cancer: a
      planning study.
AB  - BACKGROUND: Cochlea sparing can reduce late ototoxicity in head and neck cancer
      patients treated with cisplatin-based radiochemotherapy. In this situation, a
      mean cochlear dose (MCD) constraint of 10 Gy has been suggested by others based
      on the dose-effect relationship of clinical data. We aimed to investigate whether
      this is feasible for primary and postoperative radiochemotherapy in
      locoregionally advanced tumors without compromising target coverage. PATIENTS AND
      METHODS: Ten patients treated with definitive and ten patients treated with
      adjuvant intensity-modulated radiotherapy (IMRT) and concurrent chemotherapy were
      investigated. The cochleae and a planning risk volume (PRV) with a 3 mm margin
      were newly delineated, whereas target volumes and other organs at risk were not
      changed. The initial plan was recalculated with a constraint of 10 Gy (MCD) on
      the low-risk side. The quality of the resulting plan was evaluated using the
      difference in the equivalent uniform dose (EUD). RESULTS: A unilateral MCD of
      below 10 Gy could be achieved in every patient. The mean MCD was 6.8 Gy in the
      adjuvant cohort and 7.6 Gy in the definitive cohort, while the non-spared side
      showed a mean MCD of 18.7 and 30.3 Gy, respectively. The mean PRV doses were 7.8
      and 8.4 Gy for the spared side and 18.5 and 29.8 Gy for the non-spared side,
      respectively. The mean EUD values of the initial and recalculated plans were
      identical. Target volume was not compromised. CONCLUSION: Unilateral cochlea
      sparing with an MCD of less than 10 Gy is feasible without compromising the
      target volume or dose coverage in locoregionally advanced head and neck cancer
      patients treated with IMRT. A prospective evaluation of the clinical benefit of
      this approach as well as further investigation of the dose-response relationship
      for future treatment modification appears promising.

PMID- 30109364
TI  - [Drug Therapy Safety: Digital and interprofessional for and with patients].

PMID- 30109363
TI  - [3-year course after successful therapy of extreme anorexia nervosa].
AB  - Anorexia nervosa is a common psychiatric disorder in adolescents and young adults
      and is often associated with high rates of comorbidities and a chronic course of
      the disease. Additionally, it still shows the highest rates of mortality among
      all psychiatric disorders. The case presented describes a female patient with
      severe and enduring anorexia nervosa who achieved remission after strict
      adherence to inpatient treatment and showed a full recovery in the 3-year follow
      up. Shortly after achieving a minimum weight of 25 kg (171 cm, body mass index
      8.5 kg/m2) the 21-year-old, chronically ill patient was admitted to an intensive
      care unit. After a phase of stabilization and achieving a BMI of 10 kg/m2, she
      was transferred to a hospital specialized in treating eating disorders. It came
      to a full recovery of the patient including full weight restoration during
      regular follow-ups (BMI 20.0 kg/m2) and normalization of the psychopathology of
      the eating disorder. In a 3-year follow-up, the patient presented with an
      enduring and complete remission of all symptoms, which were extremely expressed
      during the illness.

PMID- 30109365
TI  - Effect of screening for type 1 diabetes on early metabolic control: the DiPiS
      study.
AB  - AIMS/HYPOTHESIS: It has been shown that children previously enrolled in follow-up
      studies have better glycaemic control during the early period after diabetes
      diagnosis. The aim of this study was to analyse glycaemic control over a longer
      period, past the period of partial remission, after diagnosis in children
      followed before diagnosis in the Swedish Diabetes Prediction in Skane (DiPiS)
      study compared with children of equal age not enrolled in pre-diabetes follow-up,
      receiving equivalent diabetes care. METHODS: HbA1c from diagnosis and for the
      following 5 years, as well as differences in insulin dosage, BMI, pump use,
      partial remission according to insulin dose-adjusted HbA1c and baseline
      demographics were compared between children who were enrolled in follow-up and
      had received information on diabetes risk (n = 51) and children not enrolled in
      follow-up (n = 78). RESULTS: The group followed before diagnosis had a higher
      proportion of first-degree relatives (FDRs) with diabetes (28% vs 5.6%; p =
      0.001) and a higher proportion of participants with mothers born in Sweden (100%
      vs 89%; p = 0.02). No significant differences in total daily insulin dose, pump
      use or other baseline sociodemographic factors were detected between the groups.
      Median HbA1c at diagnosis and at 1, 2, 3, 4 and 5 years after diabetes diagnosis
      was significantly lower in children followed before diagnosis (all p < 0.05), and
      was not related to FDR status. CONCLUSIONS/INTERPRETATION: Compared with controls
      not previously enrolled in follow-up, our study shows that children enrolled in
      longitudinal follow-up before the diagnosis of diabetes have better glycaemic
      control, measured by HbA1c, up to 5 years after diagnosis and during the initial
      period of partial remission. Improved glycaemic control in the initial years of
      living with type 1 diabetes could affect long-term outcome and complications and
      might also improve study enrolment in future longitudinal studies.

PMID- 30109366
TI  - More work is needed to better understand diabetes distress as a predictor of all
      cause mortality in type 2 diabetes.

PMID- 30109369
TI  - The negative effect of joint line elevation after total knee arthroplasty on
      outcome.
AB  - PURPOSE: Total knee arthroplasty (TKA) is widely used as a treatment for knee
      osteoarthritis. However, still up to 20% of the patients are dissatisfied. Joint
      line elevation after TKA might be a contributing factor as it alters knee
      kinematics. The aim of this study was to investigate the effect of joint line
      elevation on outcome. METHODS: A systematic review of the literature was
      performed to select studies that reported on joint line alterations after primary
      or revision TKA and outcome. Studies with comparable outcome parameters were
      included in a correlation analysis. RESULTS: In total, 396 studies were
      identified, of which 27 met the inclusion criteria. 8 studies could be included
      in the correlation analysis. Mean joint line elevation after primary TKA was 3.0
      mm and after revision TKA this was 3.6 mm. A statistically significant negative
      correlation was found between joint line elevation and the postoperative Knee
      Society Score (KSS) function score (rho = - 0.496, p < 0.001). In a pooled
      analysis, the maintained joint line revision TKA group had statistically
      significant better postoperative KSS total scores compared to an elevated joint
      line group (p < 0.001). CONCLUSION: In this systematic review, a negative
      correlation between joint line elevation and outcome was found. Furthermore,
      revision TKAs with a maintained joint line have statistically significant better
      postoperative KSS scores compared to an elevated joint line group. To achieve
      optimal outcome after TKA, restoration of the joint line is one of the parameters
      that should be pursued and introduced elevation should not exceed 4 mm. LEVEL OF
      EVIDENCE: IV.

PMID- 30109368
TI  - Post-traumatic stress disorder, anxiety and depression symptoms among adolescent
      earthquake victims: comorbidity and associated sleep-disturbing factors.
AB  - PURPOSE: Our study aimed to examine the prevalence of psychiatric symptoms and
      their comorbidity and correlation with sleep problems among adolescent survivors
      3 years after the 2013 Ya'an earthquake. METHODS: A representative sample of 6132
      adolescent students was analysed from 11 primary and high schools in the three
      counties most severely affected by the earthquake. Students were invited to
      complete the Pittsburgh Sleep Quality Index, Children's Revised Impact of Event
      Scale-13, Short Mood and Feelings Questionnaire, the Adolescent Self-Rating Life
      Events Checklist, and Screen for Child Anxiety-Related Emotional Disorders.
      RESULTS: Three years after this major earthquake, 1-month prevalence of mental
      health problems was 13.1% for PTSD, 37.3% for anxiety, and 19.8% for depression.
      Among the participants who reported PTSD, 71.5% also reported anxiety, and 49.7%
      also reported depression. At least half of those with any type of mental health
      problem reported concurrent sleeping problems. Specific sleep risk factors were
      independently associated with increased risk of PTSD, depression or anxiety.
      Girls were more likely than boys to exhibit symptoms of PTSD, depression or
      anxiety. Older adolescents were more likely to have depression and anxiety.
      CONCLUSIONS: Mental health problems are prevalent with high comorbidity and are
      associated with sleep-related problems among adolescent survivors, even years
      after the occurrence of a major earthquake. Nightmares and difficulty initiating
      sleep are independently associated with PTSD. Insufficient sleep is independently
      associated with anxiety and depression. Sleep-related problems may be effective
      targets of preventive interventions, which may need to be optimised for gender
      and age.

PMID- 30109370
TI  - Arthroscopic versus open repair of lateral ankle ligament for chronic lateral
      ankle instability: a meta-analysis.
AB  - PURPOSE: The purpose of this meta-analysis was to analyze the current comparative
      studies of arthroscopic and open techniques for lateral ankle ligament repair to
      treat chronic lateral ankle instability. METHODS: A systematic search of MEDLINE,
      EMBASE and Cochrane Library databases was performed during February 2018.
      Included studies were evaluated with regard to level of evidence and quality of
      evidence using the Modified Coleman Methodology Score. Total number of patients,
      patient age, follow-up time, gender ratio, surgical technique, surgical
      complications, complication rate, recurrent instability or revision rate,
      clinical outcome measures and percentage of patients who returned to sport at
      previous level were also evaluated. Statistical analysis was performed using
      RevMan, and a p value of < 0.05 was considered to be statistically significant.
      RESULTS: Four comparative studies for a total of 207 ankles were included. There
      was a significant difference in favor of arthroscopic repair with regard to AOFAS
      score, and there was no significant difference with regard to Karlsson score.
      There was a statistically significant difference in AOFAS score in favor of the
      arthroscopic repair (MD; 1.41, 95% CI 0.29-2.52, I2 = 0%, p < 0.05). There was no
      statistically significant difference in Karlsson score (MD; 0.00, 95% CI - 3.51
      to 3.51, I2 = 0%, n.s.). There was no statistically significant difference in
      total, nerve, or wound complications. CONCLUSIONS: The current meta-analysis
      found that short-term AOFAS functional outcome scores were significantly improved
      with arthroscopic lateral ankle repair compared to open repair. There was no
      significant difference between arthroscopic and open repair with regards to
      Karlsson functional outcome score, total complication rate, or the nerve and
      wound complication subsets with the included studies with at least 12 months of
      follow-up. However, the current evidence is still limited, and further
      prospective trials with longer follow-up are needed. LEVEL OF EVIDENCE: III.

PMID- 30109367
TI  - Regulation of IL-1 signaling by the decoy receptor IL-1R2.
AB  - The pleiotropic cytokine IL-1 mediates its biological functions via association
      with the signaling receptor IL-1R1. Despite an apparent simplicity in IL-1
      signaling activation, multiple negative regulators have been identified. The
      decoy receptor IL-1R2 (also known as CD121b) can suppress IL-1 maturation,
      sequester its active forms or hinder the signaling complex assembly. IL-1R2 is
      differentially expressed among numerous cell types and displays cis- and trans-
      modes of action. In this review, we link different forms of IL-1R2 (membrane
      bound (mIL-1R2), secreted (sIL-1R2), shedded (shIL-1R2), cytoplasmic, and
      intracellular domain (IL-1R2ICD) restricted) with their ability to interfere with
      IL-1, thereby regulating immune responses. We also discuss the intriguing
      possible function of IL-1R2 as a transcriptional regulator. Finally, we summarize
      the known impact of IL-1R2 in disease pathogenesis and discuss its potential role
      in treatment of inflammatory conditions.

PMID- 30109371
TI  - Commentary to: The urinary microbiome in patients with refractory urge
      incontinence and recurrent urinary tract infection : (Zhuoran Chen, Minh-Duy
      Phan, Lucy J Bates, Kate M Peters, Chinmoy Mukerjee, Kate H Moore, Mark
      Schembri).

PMID- 30109372
TI  - The influence of surface microbial diversity and succession on microbiologically
      influenced corrosion of steel in a simulated marine environment.
AB  - To explore how a succession of bacteria grown on steel coupons in a marine
      environment can influence their corrosion process, we designed a microcosm in
      laboratory to evaluate corrosion kinetics and microbial diversity over 30 days.
      The results described a clear influence of corrosion by a succession of different
      bacterial groups. During the initial period, 2-7 days, a sharp increase in the
      rate of corrosion was detected accompanied by the presence of Alteromonadaceae,
      Vibrionaceae, Oceanospirillaceae, Rhodobacteraceae, Rhodospirillaceae and
      Flavobacteriaceae bacteria families. After 15 days, representatives of families
      Piscirickettsiaceae and Pseudomonadaceae were also described, accompanied by a
      continuous corrosion process over the coupons. After 30 days, there was a sudden
      change in the profile of the bacteria present on the steel coupons, with a
      prevalence of Halomonadaceae family species, and establishment and continuity of
      the corrosion process by the biofilm grown on the coupons. The results describe
      differences in microbial diversity over the time, highlighting certain bacterial
      lithotrophic species that persisted for most of the experiment, through a complex
      association between bacteria and metal surfaces, which can be a new starting
      point for development and maintenance of a favorable microenvironment to
      accelerate corrosion processes.

PMID- 30109373
TI  - Cannabinoid receptor-1 signaling contributions to sign-tracking and conditioned
      reinforcement in rats.
AB  - RATIONALE: Endocannabinoids (eCBs) are critical gatekeepers of dopaminergic
      signaling, and disrupting cannabinoid receptor-1 (CB1) signaling alters DA
      dynamics to attenuate cue-motivated behaviors. Prior studies suggest that
      dopamine (DA) release plays a critical role in driving sign-tracking. OBJECTIVES:
      Here, we determine whether systemic injections of rimonabant, a CB1 receptor
      inverse agonist, during Pavlovian lever autoshaping impair the expression of sign
      tracking. We next examine whether rimonabant blocks the reinforcing properties of
      the Pavlovian lever cue in a conditioned reinforcement test. METHODS: In Exp. 1,
      we trained rats in Pavlovian lever autoshaping prior to systemic rimonabant
      injections (0, 1, 3 mg/kg) during early and late Pavlovian lever autoshaping
      sessions. In Exp. 2, we trained rats in Pavlovian lever autoshaping prior to
      systemic rimonabant injections (0, 1 mg/kg) during a conditioned reinforcement
      test. RESULTS: Rimonabant dose-dependently decreased lever contact and
      probability, and increased sign-tracker's latency to approach the lever cue early
      in Pavlovian training. With extended training, many previously goal-tracking and
      intermediate rats shifted to lever approach, which remained dose-dependently
      sensitive to rimonabant. Rimonabant attenuated cue-evoked food cup approach
      early, but not late, in conditioning, and did not affect pellet retrieval or
      consumption. The inserted lever cue served as a robust conditioned reinforcer
      after Pavlovian lever autoshaping, and 1 mg/kg rimonabant blocked conditioned
      reinforcement. CONCLUSIONS: Together, our results suggest that CB1 signaling
      mediates two critical properties of incentive stimuli; their ability to attract
      (Exp. 1) and their ability to reinforce (Exp. 2) behavior.

PMID- 30109374
TI  - [Treatment of hepatocellular carcinoma in the cirrhotic and non-cirrhotic liver].
AB  - BACKGROUND AND OBJECTIVES: The treatment of hepatocellular carcinoma (HCC)
      includes surgical, interventional and systemic approaches. This review highlights
      the importance of surgical treatment approaches in the multimodal treatment of
      HCC, based on the currently available literature, corresponding German guidelines
      as well as current developments in organ donation in Germany. RESULTS: Curative
      treatment options for HCC include liver transplantation, partial liver resection,
      and local ablative procedures depending on the lesion size. In the case of an
      early HCC in a cirrhotic liver fulfilling the Milan criteria, liver
      transplantation is the treatment of choice. In view of the organ shortage in
      Germany and improved results after partial liver resection, surgery can
      alternatively be performed in patients with a sufficient liver function. In
      selected patients with multinodular HCC, regional lymph node metastases or
      macrovascular invasion, the possibility of liver resection must be decided on an
      individual basis; however, the latter two criteria are contraindications for
      transplantation. Local ablative procedures can be considered as an alternative to
      resection in selected patients with early solitary HCC. Surgery of HCC in the non
      cirrhotic liver with a curative intent is guided by the general principles of
      oncological liver surgery. DISCUSSION: Curative treatment options for HCC include
      liver transplantation, partial liver resection and local ablative procedures.
      Current developments in the area of organ donation and technical advances in
      minimally invasive liver surgery should be included in decision-making in tumor
      boards.

PMID- 30109375
TI  - The somatosensory temporal discrimination threshold changes after a placebo
      procedure.
AB  - In a recent study, we showed that tactile perception can be enhanced by applying
      a placebo manipulation consisting of verbal suggestion and conditioning (Fiorio
      et al., Neuroscience 217:96-104, 2012). Whether this change in perception is
      related to a better tactile functioning is still unknown. Aim of this study is to
      investigate whether placebo-induced enhancement of tactile perception results in
      better somatosensory temporal discrimination threshold (STDT), as a proxy of
      tactile acuity. To this purpose, a group of subjects (experimental group) was
      verbally influenced and conditioned about the effect of an inert cream in
      enhancing tactile perception, while a control group was informed about the real
      nature of the cream. In both groups, we measured STDT before and after cream
      application, by means of pairs of electrical stimuli delivered on the index
      fingertip and separated by ascending inter-stimulus intervals. STDT was defined
      as the shortest time interval at which the two stimuli were perceived as
      separated. Results revealed an increase in subjective perception of stimulus
      intensity and a reduction of STDT only in the experimental group. This study
      proves that a placebo procedure, consisting of verbal suggestion and a short
      conditioning, can reduce the temporal discrimination threshold.

PMID- 30109377
TI  - Comparison of contrast-enhanced and diffusion-weighted MRI in assessment of the
      terminal ileum in Crohn's disease patients.
AB  - PURPOSE: The purpose of the study was to compare the performance of contrast
      enhanced (CE)-MRI and diffusion-weighted imaging (DW)-MRI in grading Crohn's
      disease activity of the terminal ileum. METHODS: Three readers evaluated CE-MRI,
      DW-MRI, and their combinations (CE/DW-MRI and DW/CE-MRI, depending on which
      protocol was used at the start of evaluation). Disease severity grading scores
      were correlated to the Crohn's Disease Endoscopic Index of Severity (CDEIS).
      Diagnostic accuracy, severity grading, and levels of confidence were compared
      between imaging protocols and interobserver agreement was calculated. RESULTS:
      Sixty-one patients were included (30 female, median age 36). Diagnostic accuracy
      for active disease for CE-MRI, DW-MRI, CE/DW-MRI, and DW/CE-MRI ranged between
      0.82 and 0.85, 0.75 and 0.83, 0.79 and 0.84, and 0.74 and 0.82, respectively.
      Severity grading correlation to CDEIS ranged between 0.70 and 0.74, 0.66 and
      0.70, 0.69 and 0.75, and 0.67 and 0.74, respectively. For each reader, CE-MRI
      values were consistently higher than DW-MRI, albeit not significantly. Confidence
      levels for all readers were significantly higher for CE-MRI compared to DW-MRI (P
      < 0.001). Further increased confidence was seen when using combined imaging
      protocols. CONCLUSIONS: There was no significant difference of CE-MRI and DW-MRI
      in determining disease activity, but the higher confidence levels may favor CE
      MRI. DW-MRI is a good alternative in cases with relative contraindications for
      the use of intravenous contrast medium.

PMID- 30109378
TI  - The "cup and ball" sign of appendico-colic intussusception.

PMID- 30109376
TI  - Mechanical Loading Differentially Affects Osteocytes in Fibulae from Lactating
      Mice Compared to Osteocytes in Virgin Mice: Possible Role for Lacuna Size.
AB  - Hormonal changes during lactation are associated with profound changes in bone
      cell biology, such as osteocytic osteolysis, resulting in larger lacunae. Larger
      lacuna shape theoretically enhances the transmission of mechanical signals to
      osteocytes. We aimed to provide experimental evidence supporting this theory by
      comparing the mechanoresponse of osteocytes in the bone of lactating mice, which
      have enlarged lacunae due to osteocytic osteolysis, with the response of
      osteocytes in bone from age-matched virgin mice. The osteocyte mechanoresponse
      was measured in excised fibulae that were cultured in hormone-free medium for 24
      h and cyclically loaded for 10 min (sinusoidal compressive load, 3000 uepsilon, 5
      Hz) by quantifying loading-related changes in Sost mRNA expression (qPCR) and
      sclerostin and beta-catenin protein expression (immunohistochemistry). Loading
      decreased Sost expression by ~ threefold in fibulae of lactating mice. The
      loading-induced decrease in sclerostin protein expression by osteocytes was
      larger in lactating mice (55% decrease +/- 14 (+/- SD), n = 8) than virgin mice
      (33% decrease +/- 15, n = 7). Mechanical loading upregulated beta-catenin
      expression in osteocytes in lactating mice by 3.5-fold (+/- 0.2, n = 6) which is
      significantly (p < 0.01) higher than the 1.6-fold increase in beta-catenin
      expression by osteocytes in fibulae from virgin mice (+/- 0.12, n = 4). These
      results suggest that osteocytes in fibulae from lactating mice with large lacunae
      may respond stronger to mechanical loading than those from virgin mice. This
      could indicate that osteocytes residing in larger lacuna show a stronger response
      to mechanical loading.

PMID- 30109379
TI  - Another point of view on 2017 PRETEXT.

PMID- 30109381
TI  - Gold nanoparticles as labels for immunochemical analysis using laser ablation
      inductively coupled plasma mass spectrometry.
AB  - In this paper, we describe the labelling of antibodies by gold nanoparticles
      (AuNPs) with diameters of 10 and 60 nm with detection by laser ablation
      inductively coupled plasma mass spectrometry (LA-ICP-MS). Additionally, the AuNPs
      labelling strategy is compared with commercially available labelling reagents
      based on MeCAT (metal coded affinity tagging). Proof of principle experiments
      based on dot blot experiments were performed. The two labelling methods
      investigated were compared by sensitivity and limit of detection (LOD). The
      absolute LODs achieved were in the range of tens of picograms for AuNP labelling
      compared to a few hundred picograms by the MeCAT labelling.

PMID- 30109380
TI  - Evolution of intramural duodenal hematomas on magnetic resonance imaging.
AB  - BACKGROUND: The magnetic resonance imaging (MRI) characteristics of evolving
      duodenal hematomas in children are unknown. OBJECTIVE: To describe the MRI
      changes exhibited by evolving duodenal hematomas and the likely mechanisms behind
      these changes. MATERIALS AND METHODS: We retrospectively reviewed the MR features
      of intramural duodenal hematomas (6 lesions, 10 examinations) studied on a 1.5-T
      MR unit. All patients had clinical histories of blunt abdominal trauma or
      endoscopic procedures and we were able to determine the time interval between the
      onset and MR imaging. We evaluated and analyzed the appearance and signal
      intensity patterns of hematomas of varying ages and we compared the results with
      those in previously reported intracranial hematomas. RESULTS: The imaging
      appearances on five examinations were consistent with presence of
      deoxyhemoglobin. Two of these lesions were hypointense on T2-weighted images and
      iso- to hyperintense on T1-weighted images. Three had heterogeneous appearances
      on both T1- and T2-weighted images, and the bulk of the hematoma progressively
      increased in size and signal intensity on T2-weighted images. On the remaining
      five examinations, one lesion was hyperintense on T1-weighted images and iso- to
      hyperintense on T2-weighted images, consistent with intracellular methemoglobin,
      and four lesions were hyperintense on both T1- and T2-weighted images, consistent
      with the presence of extracellular methemoglobin. Duodenal hematoma stages were
      slower than those of intracranial hematomas; the acute stage spanned 2-7 days,
      and early and late subacute stages occurred 10-17 days after the injury.
      CONCLUSION: Duodenal hematomas evolve like intracranial hematomas, but slower.
      Signal heterogeneity is common in the acute stage.

PMID- 30109382
TI  - New grading system for the clinical evaluation of patients with spinal vascular
      lesions.
AB  - PURPOSE: Neurointerventional approaches have improved myelopathy in patients with
      spinal vascular lesions by providing effective management, particularly when
      surgical approaches are difficult. However, there have been challenges in
      describing and comparing recovery status during the post-treatment period.
      METHODS: We evaluated 43 patients with venous congestive myelopathy (VCM) using
      Aminoff-Logue Disability Scale for gait (AL-G) and micturition (AL-M) scores.
      These results were compared with our new PSMS grading system that evaluates four
      categories (grades 0-3): pain, sensory symptoms, motor deficit, and sphincter
      change. Simple linear regression was used to identify the association or trend
      among the scales. We also calculated an overall area under the receiver operating
      characteristic curve to compare the predictive ability of the PSMS system with
      that of the previous grading system (AL-G and AL-M). RESULTS: Compared with other
      grading system, the PSMS system was more sensitively correlated with patient
      status and the results were easy to compare with previous clinical statuses
      during follow-up. The PSMS system also measured pain, which is commonly
      associated with spinal dural arteriovenous fistula and not precisely evaluated by
      other grading system. CONCLUSIONS: The new PSMS grading system for patients with
      VCM correlated well with the previously used systems and included pain
      evaluation. This new grading system is an easy tool for the evaluation and
      comparison of outcomes before and after endovascular treatment.

PMID- 30109384
TI  - ?

PMID- 30109383
TI  - Endovascular aspiration of a symptomatic free-floating common carotid artery
      thrombus.
AB  - Free-floating thrombi of the common carotid artery (CCA) are a very rare cause of
      ischemic stroke. To date, only a few reports have been described in the academic
      literature. Revascularization is indicated due to the risk of thromboembolic
      disease and hemodynamic-related stroke syndromes. Medical treatment typically
      includes anticoagulation and, in some circumstances, open surgical thrombectomy
      is an additional option. Although rarely described in the literature,
      endovascular thrombectomy is a viable treatment alternative in these patients.

PMID- 30109385
TI  - ?

PMID- 30109386
TI  - ?

PMID- 30109387
TI  - The Predictive Value of Pulse Wave Velocity for Anastomotic Leakage After
      Colorectal Surgery.
AB  - BACKGROUND: Arterial perfusion defects are a risk factor for anastomotic leakage
      (AL) following colorectal surgery. Measuring arterial stiffness using pulse wave
      velocity (PWV) is known to reflect the performance of the arterial network. The
      objective of this study was to assess the predictive value of PWV for AL after
      colorectal surgery. METHODS: A prospective monocentric study was conducted on all
      consecutive patients who underwent colorectal surgery scheduled between March 1,
      2016 and May 1, 2017. Patients were divided into two groups according to the PWV
      which was measured preoperatively using the pOpmetre(r) device: PWV+ (PWV > 10
      m/s) and PWV- (PWV <= 10 m/s). We then compared the PWV+ and PWV- groups. The
      primary endpoint was the AL rate. RESULTS: A total of 96 patients were studied,
      including 60 in the PWV- group and 36 in the PWV+ group. Patients in the PWV+
      group were more at risk of presenting with AL than those in the PWV- group (6.25
      vs 0%) (p = 0.002). There was no difference in immediate postoperative
      complications between the two groups apart from the length of hospital stay. PWV
      predicted the appearance of AL with a sensitivity of and a negative predictive
      value of 100%. CONCLUSION: Measuring PWV could be a used as a predictive
      examination in the early detection of AL after colorectal surgery.

PMID- 30109388
TI  - Safety Culture and Perioperative Quality at the Volta River Authority Hospital in
      Akosombo, Ghana.
AB  - BACKGROUND: The Volta River Authority Hospital (VRAH) is a district hospital
      associated with a large public works project in Akosombo, Ghana, that has
      developed a reputation for high-quality care. We hypothesized that this stems
      from a culture of safety and standardized processes typical of high-risk
      engineering environments. To investigate this, we evaluated staff and patient
      perceptions of safety and quality, as well as perioperative process variability.
      MATERIALS AND METHODS: The Safety Attitudes Questionnaire (SAQ) and Hospital
      Consumer Assessment of Healthcare Providers and Systems (HCAHPS) surveys were
      used to evaluate staff and patient perceptions of safety. Perioperative general
      surgery and obstetrical procedure observations generated process maps, which were
      analyzed for variability and waste. RESULTS: Thirty-one SAQs were administered.
      83% of workers held a positive perception of teamwork, and 77.4% held a positive
      perception of safety culture. Fifteen HCAHPS surveys of surgical inpatients
      showed a median hospital rating of 10 [IQR 8.5-10] on a ten-point scale. 90% gave
      maximal scores for pain management and 84.4% for nurse communication. Ten general
      surgery and obstetrical procedures were observed for which process map analysis
      was notable for no consistent waste steps and 100% adherence to the World Health
      Organization Safe Surgery Checklist. CONCLUSIONS: Surveys suggest an
      institutional commitment to safety with strong teamwork culture and patient
      communication. Perioperative process mapping supports this culture, with low
      levels of variability and waste, and is useful for evaluating standardization of
      care. VRAH demonstrates the feasibility of delivering high standards of
      perioperative care in a low-resource setting.

PMID- 30109389
TI  - Ten Years and Counting: Sustaining Effectiveness of the Surgical Safety Checklist
      Through Ongoing Implementation Efforts.

PMID- 30109390
TI  - Time to Readmission and Mortality Among Patients Undergoing Liver and Pancreatic
      Surgery.
AB  - BACKGROUND: The impact of time to readmission (TTR) on post-discharge mortality
      has not been well examined. We sought to define the impact of TTR on
      postoperative mortality after liver or pancreas surgery. METHODS: A retrospective
      cohort analysis of liver and pancreas surgical patients was conducted using 2013
      2015 Medicare Provider Analysis and Review database. Patients were subdivided
      into TTR groups: 1-5 days, 6-15, 15-30, 31-60, 61-90, and no readmission. The
      association of index complication, readmission causes, TTR, and mortality was
      assessed. RESULTS: Among 18,177 patients, a total of 4485 (24.7%) patients were
      readmitted within 90 days of discharge. Major causes for readmission differed
      across TTR groups. Patients readmitted within 1-15 days were more likely to be
      readmitted for postoperative infection compared with patients who had a late
      readmission (1-5 days: 63.1% vs. 6-15 days: 65.0% vs. 61-90 days: 39.3%; P <
      0.001). In contrast, causes of late readmissions were more likely related to
      gastrointestinal complications (1-5 days: 28.9% vs. 61-90 days: 39.7%; P <
      0.001). Compared with no readmission, 180-day mortality was highest among
      patients readmitted within 16-30 days (aOR 3.60; 95% CI 2.94-4.41). Among
      patients with index complications, patients who were readmitted within 1-5 days
      had a higher risk-adjusted 180-day mortality than late readmission (1-5 days:
      37.3% vs. 61-90 days: 27.1%) (P < 0.001). CONCLUSIONS: Among patients who were
      readmitted, the incidence of mortality increased with TTR up to 60 days after
      discharge yet decreased thereafter. The relation of TTR and mortality was
      particularly pronounced among those patients who had an index complication.
      Future efforts should consider TTR when identifying specific approaches to
      decrease readmission.

PMID- 30109391
TI  - Mapping adult plant stem rust resistance in barley accessions Hietpas-5 and GAW
      79.
AB  - Key message Major stem rust resistance QTLs proposed to be Rpg2 from Hietpas-5
      and Rpg3 from GAW-79 were identified in chromosomes 2H and 5H, respectively, and
      will enhance the diversity of stem rust resistance in barley improvement
      programs. Stem rust is a devastating disease of cereal crops worldwide. In barley
      (Hordeum vulgare ssp. vulgare), the disease is caused by two pathogens: Puccinia
      graminis f. sp. secalis (Pgs) and Puccinia graminis f. sp. tritici (Pgt). In
      North America, the stem rust resistance gene Rpg1 has protected barley from
      serious losses for more than 60 years; however, widely virulent Pgt races from
      Africa in the Ug99 group threaten the crop. The accessions Hietpas-5 (CIho 7124)
      and GAW-79 (PI 382313) both possess moderate-to-high levels of adult plant
      resistance to stem rust and are the sources of the resistance genes Rpg2 and
      Rpg3, respectively. To identify quantitative trait loci (QTL) for stem rust
      resistance in Hietpas-5 and GAW-79, two biparental populations were developed
      with Hiproly (PI 60693), a stem rust-susceptible accession. Both populations were
      phenotyped to the North American Pgt races of MCCFC, QCCJB, and HKHJC in St.
      Paul, Minnesota, and to African Pgt races (predominately TTKSK in the Ug99 group)
      in Njoro, Kenya. In the Hietpas-5/Hiproly population, a major effect QTL was
      identified in chromosome 2H, which is proposed as the location for Rpg2. In the
      GAW-79/Hiproly population, a major effect QTL was identified in chromosome 5H and
      is the proposed location for Rpg3. These QTLs will enhance the diversity of stem
      rust resistance in barley improvement programs.

PMID- 30109393
TI  - Meiotic homoeologous recombination-based mapping of wheat chromosome 2B and its
      homoeologues in Aegilops speltoides and Thinopyrum elongatum.
AB  - KEY MESSAGE: We physically dissected and mapped wheat chromosome 2B and its
      homoeologues in Aegilops speltoides and Thinopyrum elongatum based on meiotic
      homoeologous recombination, providing a unique physical framework for genome
      studies. Common wheat has a large and complex genome with narrow genetic
      diversity and various degrees of recombination between the A, B, and D
      subgenomes. This has limited the homologous recombination-based genome studies in
      wheat. Here, we exploited meiotic homoeologous recombination for molecular
      mapping of wheat chromosome 2B and its homoeologue 2S from Aegilops speltoides
      and 2E from Thinopyrum elongatum. The 2B-2S and 2B-2E recombination was induced
      by the ph1b mutant, and recovered using molecular markers and fluorescent genomic
      in situ hybridization (FGISH). A total of 112 2B-2S and 87 2B-2E recombinants
      involving different chromosome regions were developed and physically delineated
      by FGISH. The 2B-2S and 2B-2E recombination hotspots mapped to the subterminal
      regions on both arms. Recombination hotspots with the highest recombination rates
      mapped to the short arms. Eighty-three 2B-2S and 67 2B-2E recombinants were
      genotyped using the wheat 90 K SNP arrays. Based on the genotyping results and
      FGISH patterns of the recombinants, chromosomes 2B, 2S, and 2E were partitioned
      into 93, 66, and 46 bins, respectively. In total, 1037 SNPs physically mapped
      onto distinct bins of these three homoeologous chromosomes. A homoeologous
      recombination-based bin map was constructed for chromosome 2B, providing a unique
      physical framework for genome studies in wheat and its relatives. Meiotic
      homoeologous recombination also facilitates gene introgression to diversify the
      wheat genome for germplasm development. Therefore, homoeologous recombination
      based studies enhance understanding of the wheat genome and its homoeologous
      counterparts from wild grasses, and expand the genetic variability of the wheat
      genome.

PMID- 30109392
TI  - A 55 K SNP array-based genetic map and its utilization in QTL mapping for
      productive tiller number in common wheat.
AB  - KEY MESSAGE: A high-density genetic map constructed with a wheat 55 K SNP array
      was highly consistent with the physical map of this species and it facilitated
      the identification of a novel major QTL for productive tiller number. Productive
      tiller number (PTN) plays a key role in wheat grain yield. In this study, a
      recombinant inbred line population with 199 lines derived from a cross between
      '20828' and 'Chuannong16' was used to construct a high-density genetic map using
      wheat 55 K single nucleotide polymorphism (SNP) array. The constructed genetic
      map contains 12,109 SNP markers spanning 3021.04 cM across the 21 wheat
      chromosomes. The orders of the genetic and physical positions of these markers
      are generally in agreement, and they also match well with those based on the 660
      K SNP array from which the one used in this study was derived. The ratios of SNPs
      located in each of the wheat deletion bins were similar among the wheat 9 K, 55
      K, 90 K, 660 K and 820 K SNP arrays. Based on the constructed maps, a novel major
      quantitative trait locus QPtn.sau-4B for PTN was detected across multi
      environments in a 0.55 cM interval on 4B and it explained 17.23-45.46% of the
      phenotypic variance. Twenty common genes in the physical interval between the
      flanking markers were identified on chromosome 4B of 'Chinese Spring' and wild
      emmer. These results indicate that wheat 55 K SNP array could be an ideal tool in
      primary mapping of target genes and the identification of QPtn.sau-4B laid a
      foundation for the following fine mapping and cloning work.

PMID- 30109394
TI  - Impact of disulfide bonds on the folding and refolding capability of a novel
      thermostable GH45 cellulase.
AB  - A new cellulase (TaCel45) of glycoside hydrolase family 45 was identified in the
      thermophilic fungus Thielavia arenaria XZ7 and was successfully expressed in
      Pichia pastoris. The specific activities of TaCel45 towards lichenin, sodium
      carboxymethylcellulose (CMC-Na), and barley beta-glucan were 769, 498, and 486
      U/mg protein, respectively, which are higher than the values for all other
      reported GH45 cellulases. TaCel45 had maximum activity at pH 5.0-6.0 and 60-65 
      degrees C with barley beta-glucan and CMC-Na as substrates and had a melting
      temperature (Tm) of 68.4  degrees C. However, TaCel45 exhibited extraordinary
      thermostability at 90 and 100  degrees C, retaining more than 70 and 45% of its
      activity after a 1-h incubation, respectively. Seven mutants (C11S, C12S, C16S,
      C31S, C171S, C193S, and C203S) were then constructed to investigate the effects
      of each disulfide bond on the structure, activity, and stability of TaCel45. As a
      result, six disulfide bonds (C11-C136, C16-C87, C31-C57, C88-C203, C90-C193, and
      C160-Cy171) were found to be indispensable for the folding, secretion, and
      activity of TaCel45, while C12-C48 was critical for thermal adaptation and
      refolding. The mutant C12S showed decreased optimal temperature and Tm values of
      50 and 60.2  degrees C, respectively, and retained less than 50% of the thermal
      refolding ability of the wild type. Overall, this study demonstrated that
      disulfide bonds play a vital role in the folding and refolding capability and
      thermostability of this GH45 cellulase.

PMID- 30109396
TI  - Rational protein design for thermostabilization of glycoside hydrolases based on
      structural analysis.
AB  - Glycosidases are used in the food, chemical, and energy industries. These
      proteins are some of the most frequently used such enzymes, and their
      thermostability is essential for long-term and/or repeated use. In addition to
      thermostability, modification of the substrate selectivity and improvement of the
      glycosidase activities are also important. Thermostabilization of enzymes can be
      performed by directed evolution via random mutagenesis or by rational design via
      site-directed mutagenesis; each approach has advantages and disadvantages. In
      this paper, we introduce thermostabilization of glycoside hydrolases by rational
      protein design using site-directed mutagenesis along with X-ray crystallography
      and simulation modeling. We focus on the methods of thermostabilization of
      glycoside hydrolases by linking the N- and C-terminal ends, introducing disulfide
      bridges, and optimizing beta-turn structures to promote hydrophobic interactions.

PMID- 30109395
TI  - Characteristics and molecular determinants of a highly selective and efficient
      glycyrrhizin-hydrolyzing beta-glucuronidase from Staphylococcus pasteuri 3I10.
AB  - Glycyrrhizin (GL), the principal sweet-tasting bioactive ingredient of licorice
      (root of Glycyrrhiza glabra), shows poor oral absorption and gut microbial
      transformation of GL to glycyrrhetinic acid (GA) plays a major role for its
      multiple pharmacological effects. Co-administration of GL-hydrolyzing bacteria
      appears to be a feasible strategy to enhance GA exposure. This study reported a
      gut bacterial strain Staphylococcus pasteuri 3I10 which exhibited moderate p
      nitrophenyl-beta-D-glucuronide (PNPG)-hydrolyzing activity but low GL
      deglucuronidation activity in its crude lysate. The gus gene encoding S. pasteuri
      3I10 beta-glucuronidase was successfully cloned and overexpressed in Escherichia
      coli BL21(DE3). The purified beta-glucuronidase (SpasGUS) was 71 kDa and showed
      optimal pH and temperature at 6.0 and 50  degrees C, respectively. Comparing to
      E. coli beta-glucuronidase (EcoGUS), SpasGUS displayed lower velocity and
      affinity to PNPG hydrolysis (Vmax 16.1 +/- 0.9 vs 140.0 +/- 4.1 MUmolmin-1 mg-1;
      Km 469.4 +/- 73.4 vs 268.0 +/- 25.8 MUM), but could selectively convert GL to GA
      at much higher efficiency (Vmax 0.41 +/- 0.011 vs 0.005 +/- 0.002 MUmolmin-1 mg
      1; Km 116.9 +/- 15.4 vs 53.4 +/- 34.8 MUM). Molecular docking studies suggested
      SpasGUS formed hydrogen bond interactions with the glucuronic acids at Asn414,
      Glu415 and Leu450, and Val159, Tyr475, Ala368, and Phe367 provided a hydrophobic
      environment for enhanced activity. Two special substrate interaction loops near
      the binding pocket of SpasGUS (loop 1 beta-glucuronidase) may account for the
      selective and efficient bioconversion of GL to GA, predicting that loop 1 beta
      glucuronidases show high possibility in processing GL than mini-loop 1 and loop 2
      beta-glucuronidases. These findings support potential applications of SpasGUS in
      cleaving GL to facilitate GA production in vivo or in pharmaceutical industry.

PMID- 30109397
TI  - Recent advances in metabolic engineering of Corynebacterium glutamicum for
      bioproduction of value-added aromatic chemicals and natural products.
AB  - Recent progress in synthetic and systems metabolic engineering technologies has
      explored the potential of microbial cell factories for the production of
      industrially relevant bulk and fine chemicals from renewable biomass resources in
      an eco-friendly manner. Corynebacterium glutamicum, a workhorse for industrial
      amino acid production, has currently evolved into a promising microbial platform
      for bioproduction of various natural and non-natural chemicals from renewable
      feedstocks. Notably, it has been recently demonstrated that metabolically
      engineered C. glutamicum can overproduce several commercially valuable aromatic
      and related chemicals such as shikimate, 4-hydroxybenzoate, and 4-aminobenzoate
      from sugars at remarkably high titer suitable to commercial application. On the
      other hand, overexpression and/or extension of its endogenous metabolic pathways
      by integrating heterologous metabolic pathways enabled production of structurally
      intricate and valuable natural chemicals like plant polyphenols, carotenoids, and
      fatty acids. In this review, we summarize recent advances in metabolic
      engineering of C. glutamicum for production of those value-added aromatics and
      other natural products, which highlights high potential and the versatility of
      this microbe for bioproduction of diverse chemicals.

PMID- 30109398
TI  - Solvent production from xylose.
AB  - Xylose is the second most abundant sugar derived from lignocellulose; it is
      considered less desirable than glucose for fermentation, and strategies that
      specifically increase xylose utilization in wild type or engineered cells are
      goals for biofuel production. Issues arise with xylose utilization because of
      carbohydrate catabolite repression, which is the preferential utilization of
      glucose relative to xylose in fermentations with both pure and mixed cultures.
      Taken together the low substrate utilization rates and solvent yields with xylose
      compared to glucose, many industrial fermentations ignore the xylolytic portion
      of the reaction in lieu of methods to maintain high glucose. This is shortsighted
      given the massive potential for xylose generation from a number of sustainable
      biomass feedstocks, based on utilization of the hemicellulose fraction(s) that
      enter pretreatment. A number of strategies have been developed in recent years to
      address xylose utilization and solvent production from xylose in systems with
      just xylose, or in systems with mixtures of glucose plus xylose, which are more
      typical of pretreated lignocellulose. The approaches vary in terms of complexity,
      stability, and ease of introduction to existing fermentation infrastructure
      (i.e., so-called drop-in fermentation strategies). Some approaches can be
      considered traditional engineering approaches (e.g., change the reaction
      conditions), while others are more subtle cellular approaches to eliminate the
      impacts of catabolite repression. Finally, genetic engineering has been used to
      increase xylose utilization, although this can be considered a relatively nascent
      approach compared to manipulations completed to date for glucose utilization.

PMID- 30109400
TI  - Delivering PET imaging results to cancer patients: steps for handling ethical
      issues.

PMID- 30109399
TI  - Enhancing L-malate production of Aspergillus oryzae FMME218-37 by improving
      inorganic nitrogen utilization.
AB  - Microbial L-malate production from renewable feedstock is a promising alternative
      to petroleum-based chemical synthesis. However, high L-malate production of
      Aspergillus oryzae was achieved to date using organic nitrogen, with inorganic
      nitrogen still unable to meet industrial applications. In the current study, we
      constructed a screening system and nitrogen supply strategy to improve L-malate
      production with ammonium sulphate [(NH4)2SO4] as the sole nitrogen source. First,
      we generated and identified a high-producing mutant FMME218-37, which stably
      boosted L-malate production from 30.73 to 78.12 g/L, using a combined screening
      system with morphological characteristics. Then, by analyzing the fermentation
      parameters and physiological characteristics, we further speculated the key
      factor was the unbalance of carbon and nitrogen absorption. Finally, the titer
      and productivity of L-malate was increased to 95.2 g/L and 0.57 g/(L h) by
      regulating the nitrogen supply module to balance carbon and nitrogen absorption,
      which represented the highest level in A. oryzae with (NH4)2SO4 as nitrogen
      source achieved to date. Moreover, our findings using a low-cost substrate may
      lead to building an economical cell factory of A. oryzae for L-malate production.

PMID- 30109401
TI  - Region-by-region analysis of PET, MRI, and histology in en bloc-resected
      oligodendrogliomas reveals intra-tumoral heterogeneity.
AB  - PURPOSE: Oligodendrogliomas are heterogeneous tumors in terms of imaging
      appearance, and a deeper understanding of the histopathological tumor
      characteristics in correlation to imaging parameters is needed. We used PET-to
      MRI-to-histology co-registration with the aim of studying intra-tumoral 11C
      methionine (MET) uptake in relation to tumor perfusion and the protein expression
      of histological cell markers in corresponding areas. METHODS: Consecutive
      histological sections of four tumors covering the entire en bloc-removed tumor
      were immunostained with antibodies against IDH1-mutated protein (tumor cells),
      Ki67 (proliferating cells), and CD34 (blood vessels). Software was developed for
      anatomical landmarks-based co-registration of subsequent histological images,
      which were overlaid on corresponding MET PET scans and MRI perfusion maps.
      Regions of interest (ROIs) on PET were selected throughout the entire tumor
      volume, covering hot spot areas, areas adjacent to hot spots, and tumor borders
      with infiltrating zone. Tumor-to-normal tissue (T/N) ratios of MET uptake and
      mean relative cerebral blood volume (rCBV) were measured in the ROIs and protein
      expression of histological cell markers was quantified in corresponding regions.
      Statistical correlations were calculated between MET uptake, rCBV, and quantified
      protein expression. RESULTS: A total of 84 ROIs were selected in four
      oligodendrogliomas. A significant correlation (p < 0.05) between MET uptake and
      tumor cell density was demonstrated in all tumors separately. In two tumors, MET
      correlated with the density of proliferating cells and vessel cell density. There
      were no significant correlations between MET uptake and rCBV, and between rCBV
      and histological cell markers. CONCLUSIONS: The MET uptake in hot spots, outside
      hotspots, and in infiltrating tumor edges unanimously reflects tumor cell
      density. The correlation between MET uptake and vessel density and density of
      proliferating cells is less stringent in infiltrating tumor edges and is probably
      more susceptible to artifacts caused by larger blood vessels surrounding the
      tumor. Although based on a limited number of samples, this study provides
      histological proof for MET as an indicator of tumor cell density and for the lack
      of statistically significant correlations between rCBV and histological cell
      markers in oligodendrogliomas.

PMID- 30109402
TI  - Differences in gray and white matter 18F-THK5351 uptake between behavioral
      variant frontotemporal dementia and other dementias.
AB  - PURPOSE: We investigated the regional distribution of 18F-THK5351 uptake in gray
      (GM) and white matter (WM) in patients with behavioral-variant frontotemporal
      dementia (bvFTD) and compared it with that in patients with Alzheimer's disease
      (AD) or semantic dementia (SD). METHODS: 18F-THK-5351 positron emission
      tomography (PET), 18F-florbetaben PET, magnetic resonance imaging, and
      neuropsychological testing were performed in 103 subjects including 30, 24, 9,
      and 8 patients with mild cognitive impairment, AD, bvFTD, and SD, respectively,
      and 32 normal subjects. Standardized uptake value ratios (SUVRs) of 18F-THK-5351
      PET images were measured from six GM and WM regions using cerebellar GM as
      reference. GM and WM SUVRs and WM/GM ratios, the relationship between GM SUVR and
      WM/GM ratio, and correlation between SUVR and cognitive function were compared.
      RESULTS: In AD, both parietal GM (p < 0.001) and WM (p < 0.001) SUVRs were higher
      than in bvFTD. In AD and SD, the WM/GM ratio decreased as the GM SUVR increased,
      regardless of lobar region. In AD, memory function correlated with parietal GM
      (rho = -0.74, p < 0.001) and WM (rho = -0.53, p < 0.001) SUVR. In SD, language
      function correlated with temporal GM SUVR (rho = -0.69, p = 0.006). The frontal
      WM SUVR was higher in bvFTD than in AD (p = 0.003) or SD (p = 0.017). The frontal
      WM/GM ratio was higher in bvFTD than in AD (p < 0.001). In bvFTD, the WM/GM ratio
      increased more prominently than the GM SUVR only in the frontal lobe (R2 =
      0.026). In bvFTD, executive function correlated with frontal WM SUVR (rho = 
      0.64, p = 0.014). CONCLUSIONS: Frontal WM 18F-THK5351 uptake was higher in bvFTD
      than in other dementias. The increase in frontal WM uptake was greater than the
      increase in GM uptake and correlated with executive function. This suggests that
      frontal lobe WM 18F-THK5351 uptake reflects neuropathological differences between
      bvFTD and other dementias.

PMID- 30109403
TI  - Femoral anteversion does not predict redislocation in children with hip dysplasia
      treated by closed reduction.
AB  - PURPOSE: Increased femoral anteversion can be associated with hip instability,
      redislocation after closed reduction, and subsequent early degenerative
      arthritis. Our study compared proximal femoral anteversion of affected and
      unaffected sides of patients with unilateral developmental dysplasia of the hip
      (DDH) on two-dimensional computed tomography. The primary aim was to evaluate
      whether femoral anteversion at the time of treatment affected the outcome of
      patients with unilateral DDH treated by closed reduction. METHODS: A
      retrospective review of 89 patients (82 females; 53 left; mean age: 26.6 months)
      with unilateral DDH was performed. Anteversion angle (AA) of the femur and
      acetabular index (AI) of both affected (AAa; AIa) and unaffected (AAu; AIu) hips
      were measured on two-dimensional CT scan performed no more than seven days prior
      to the index surgical procedure. RESULTS: Among the 89 patients, 50 underwent
      closed reduction (56.2%), 38 underwent open reduction with or without pelvic
      osteotomy (42.7%), and one patient refused treatment (1.1%). Overall, the mean
      AAa was 28.1 degrees  +/- 10.2 degrees  (range: 6.3 degrees -54 degrees ) and
      mean AAu was 25.2 degrees  +/- 9.9 degrees  (range: 1.9 degrees -52.5 degrees )
      (t = 3.2, p = 0.002). Tonnis type 2 hips did not show any statistically
      significant difference between AAa and AAu (p = 0.386), while Tonnis types 3 and
      4 hips had significantly higher AAa than did AAu (t = 3.7, p = 0.001). There were
      significant correlations between age and AAa (coefficient = 0.4; p < 0.001) and
      AAu (coefficient = 0.304; p = 0.004). Correlation analysis showed that AIa did
      not improve with age in any Tonnis group (r: - 0.24, p = 0.823; F = 0.039, p =
      0.962). AAa, AIa, AAD, AID, and Tonnis grade distribution were similar in
      patients with good (no redislocation) and poor outcomes (redislocation) (p >
      0.05). CONCLUSION: In patients with unilateral DDH, anteversion angle (AA) was
      found to be significantly different between affected and unaffected sides.
      However, the difference had very limited or no clinical significance, as
      redislocation/sub-luxation was not influenced by AA values.

PMID- 30109404
TI  - Intra-articular injection of autologous adipose-derived stromal vascular
      fractions for knee osteoarthritis: a double-blind randomized self-controlled
      trial.
AB  - OBJECTIVE: The purpose of this study was to compare the clinical and radiological
      efficacy of autologous adipose-derived stromal vascular fraction (SVF) versus
      hyaluronic acid in patients with bilateral knee osteoarthritis. METHODS: Sixteen
      patients with bilateral symptomatic knee osteoarthritis (K-L grade II to III;
      initial pain evaluated at four or greater on a ten-point VAS score) were enrolled
      in this study, which were randomized into two groups. Each patient received 4-ml
      autologous adipose-derived SVF treatment (group test, n = 16) in one side of knee
      joints and a single dose of 4-ml hyaluronic acid treatment (group control, n =
      16) in the other side. The clinical evaluations were performed pre-operatively
      and post-operatively at one month, three months, six months, and 12-months follow
      up visit, using the ten-point visual analog scale (VAS), the Western Ontario and
      McMaster Universities Osteoarthritis Index (WOMAC), and the knee range of motion
      (ROM). The whole-organ assessment of the knees was performed with whole-organ
      magnetic resonance imaging score (WORMS) based on MRI at baseline, six months and
      12-months follow-up. The articular repair tissue was assessed quantitatively and
      qualitatively by magnetic resonance observation of cartilage repair tissue
      (MOCART) score based on follow-up MRI at six months and 12 months. RESULTS: No
      significant baseline differences were found between two groups. Safety was
      confirmed with no severe adverse events observed during 12-months follow-up. The
      SVF-treated knees showed significantly improvement in the mean VAS, WOMAC scores,
      and ROM at 12-months follow-up visit compared with the baseline. In contrast, the
      mean VAS, WOMAC scores, and ROM of the control group became even worse but not
      significant from baseline to the last follow-up visit. WORMS and MOCART
      measurements revealed a significant improvement of articular cartilage repair in
      SVF-treated knees compared with hyaluronic acid-treated knees. CONCLUSION: The
      results of this study suggest that autologous adipose-derived SVF treatment is
      safe and can effectively relief pain, improve function, and repair cartilage
      defects in patients with knee osteoarthritis.

PMID- 30109405
TI  - Influence of the post-operative axis on the clinical results of total knee
      replacement for severe varus deformities: does a slight residual varus improve
      the results?
AB  - PURPOSE: Some recent articles have suggested that in the case of large varus
      deformity, it may be advantageous to leave some residual post-operative varus as
      a means of improving functional outcome. The objective of this study is to
      compare the results of total knee replacement (TKR) performed for significant
      varus deformity (HKA < 170 degrees ) where there is a residual post-operative
      varus (HKA < 180 degrees ) to the results of TKR for significant varus deformity
      with either neutral post-operative (HKA = 180 degrees ) or mild valgus post
      operative alignment (HKA > 180 degrees ). METHODS: This series was made up of 208
      knees. The mean pre-operative HKA angle was 166 +/- 3 degrees  (154-169 degrees
      ), of which 150 were followed up for a mean 8.5 years (58 lost to follow-up).
      Based on post-operative radiographs, two groups were formed: group 1 (88 knees)
      in which post-operative alignment was 177.8 +/- 1 degrees  (175-179 degrees ) and
      group 2 (62 knees) in which post-operative alignment was 181 +/- 1 degrees  (180
      184 degrees ). RESULTS: The mean international knee society (IKS) score for group
      1 was 178.8 +/- 22 points (113-200) and 181.7 +/- 22 points (95-200) for group 2.
      Oxford knee score was 20.4 +/- 9 points (12-45) in group 1 and 19.2 +/- 9 (12-50)
      in group 2. The results were slightly better in group 2 (in slight valgus) but
      this difference was not statistically significant (p = 0.44 and 0.4). CONCLUSION:
      The results of knee replacement performed for severe varus deformity are not
      adversely affected by post-operative valgus alignment. There is in fact a trend
      towards superior results for neutral or valgus alignment than slight residual
      varus, but this difference was not statistically significant.

PMID- 30109408
TI  - Trans-Catheter Aspiration of Systemic Air Embolism Causing Cardiac Compromise
      During CT-Guided Lung Biopsy, a Potentially Lifesaving Maneuver.
AB  - Systemic artery embolism is a rare complication of CT-guided lung biopsy.
      Immediate clinical and radiological recognitions are crucial for rapid
      intervention and prevention of fatal outcome. Although hyperbaric oxygen is the
      suggested treatment of mildly symptomatic systemic artery embolization,
      aspiration of air should be considered as part of the management in cases of
      cardiac arrest.

PMID- 30109407
TI  - Anatomy, development, and plasticity of the neurosecretory hypothalamus in
      zebrafish.
AB  - The paraventricular nucleus (PVN) of the hypothalamus harbors diverse
      neurosecretory cells with critical physiological roles for the homeostasis.
      Decades of research in rodents have provided a large amount of information on the
      anatomy, development, and function of this important hypothalamic nucleus.
      However, since the hypothalamus lies deep within the brain in mammals and is
      difficult to access, many questions regarding development and plasticity of this
      nucleus still remain. In particular, how different environmental conditions,
      including stress exposure, shape the development of this important nucleus has
      been difficult to address in animals that develop in utero. To address these open
      questions, the transparent larval zebrafish with its rapid external development
      and excellent genetic toolbox offers exciting opportunities. In this review, we
      summarize recent information on the anatomy and development of the neurosecretory
      preoptic area (NPO), which represents a similar structure to the mammalian PVN in
      zebrafish. We will then review recent studies on the development of different
      cell types in the neurosecretory hypothalamus both in mouse and in fish. Lastly,
      we discuss stress-induced plasticity of the PVN mainly discussing the data
      obtained in rodents, but pointing out tools and approaches available in zebrafish
      for future studies. This review serves as a primer for the currently available
      information relevant for studying the development and plasticity of this
      important brain region using zebrafish.

PMID- 30109406
TI  - Spontaneous nasal cerebrospinal fluid leaks: management of 24 patients over 11
      years.
AB  - PURPOSE: Most cases of non-traumatic nasal cerebrospinal fluid (CSF) leaks occur
      spontaneously without any obvious reason. Severe and life-threatening
      complications are possible consequences. Endoscopic repair is considered the gold
      standard; however, diagnosis and therapy of these CSF leaks stay challenging.
      METHODS: In this retrospective analysis, patients who presented with spontaneous
      nasal CSF leaks from 2006 to 2017 were included. Symptoms, diagnostics,
      localization of the skull base defect, surgical method, outcome, and
      postoperative treatment were recorded. RESULTS: Twenty four patients were
      included. 8 patients presented with symptoms of meningitis. The skull base
      defects were most commonly located in the anterior ethmoid roof-especially in the
      cribriform plate-and in the lateral part of the sphenoid sinus. 21 patients had a
      BMI above 25. In only 13 cases the defect could be detected preoperatively via
      computed tomography or additional magnetic resonance imaging. In all patients
      intraoperative visualization of the CSF leak was possible using intrathecal
      application of sodium-fluorescein. Endoscopic repair was the initial surgical
      method for all patients and proved to be successful in 80% of the cases. In most
      cases surgical revision was performed endoscopically; however, in two patients an
      open transpterygoidal approach was necessary. CONCLUSIONS: Spontaneous nasal CSF
      leaks often initially present with symptomatic meningitis. Imaging does not
      always clearly identify the skull base defect. Common localizations are the
      anterior ethmoid roof and the lateral sphenoid sinus. Obesity seems to be a
      predisposing factor. In most cases, endoscopic repair with low morbidity is
      possible; however, an individualized approach is necessary.

PMID- 30109410
TI  - Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology,
      clinical presentation, diagnosis and therapy.
AB  - Hereditary hypophosphatemic rickets with hypercalciuria (HHRH; OMIM: 241530) is a
      rare autosomal recessive disorder with an estimated prevalence of 1:250,000 that
      was originally described by Tieder et al. Individuals with HHRH carry compound
      heterozygous or homozygous (comp/hom) loss-of-function mutations in the sodium
      phosphate co-transporter NPT2c. These mutations result in the development of
      urinary phosphate (Pi) wasting and hypophosphatemic rickets, bowing, and short
      stature, as well as appropriately elevated 1,25(OH)2D levels, which sets this
      fibroblast growth factor 23 (FGF23)-independent disorder apart from the more
      common X-linked hypophosphatemia. The elevated 1,25(OH)2D levels in turn result
      in hypercalciuria due to enhanced intestinal calcium absorption and reduced
      parathyroid hormone (PTH)-dependent calcium-reabsorption in the distal renal
      tubules, leading to the development of kidney stones and/or nephrocalcinosis in
      approximately half of the individuals with HHRH. Even heterozygous NPT2c
      mutations are frequently associated with isolated hypercalciuria (IH), which
      increases the risk of kidney stones or nephrocalcinosis threefold in affected
      individuals compared with the general population. Bone disease is generally
      absent in individuals with IH, in contrast to those with HHRH. Treatment of HHRH
      and IH consists of monotherapy with oral Pi supplements, while active vitamin D
      analogs are contraindicated, mainly because the endogenous 1,25(OH)2D levels are
      already elevated but also to prevent further worsening of the hypercalciuria.
      Long-term studies to determine whether oral Pi supplementation alone is
      sufficient to prevent renal calcifications and bone loss, however, are lacking.
      It is also unknown how therapy should be monitored, whether secondary
      hyperparathyroidism can develop, and whether Pi requirements decrease with age,
      as observed in some FGF23-dependent hypophosphatemic disorders, or whether this
      can lead to osteoporosis.

PMID- 30109409
TI  - Piriformospora indica cell wall modulates gene expression and metabolite profile
      in Linum album hairy roots.
AB  - MAIN CONCLUSION: Elicitation of Linum album hairy roots by Piriformospora indica
      cell wall induced the target genes and specific metabolites in phenylpropanoid
      pathway and shifted the amino acid metabolism toward the phenolic compound
      production. Plants have evolved complex mechanisms to defend themselves against
      various biotic stresses. One of these responses is the production of metabolites
      that act as defense compounds. Manipulation of plant cell cultures by biotic
      elicitors is a useful strategy for improving the production of valuable secondary
      metabolites. This study focused on hairy root culture of Linum album, an
      important source for lignans. The effects of cell wall elicitor extracted from
      Piriformospora indica on phenylpropanoid derivatives were evaluated to identify
      metabolic traits related to biotic stress tolerance. Significant increases in
      lignin, lignans; lariciresinol, podophyllotoxin, and 6-methoxy podophyllotoxin;
      phenolic acids: cinnamic acid, ferulic acid, and salicylic acid; flavonoids:
      myricetin, kaempferol, and diosmin were observed in response to the fungal
      elicitor. In addition, the gene expression levels of phenylalanine ammonia-lyase,
      cinnamyl alcohol dehydrogenase, cinnamoyl-CoA reductase, and pinoresinol
      lariciresinol reductase significantly increased after elicitation. The
      composition of free amino acids was altered under the elicitation. Phenylalanine
      and tyrosine, as precursors of phenylpropanoid metabolites, were increased, but
      alanine, serine, and glutamic acid significantly decreased in response to the
      fungal elicitor, suggesting that the amino acid pathway may be shifted toward
      biosynthesis of aromatic amino acids and precursors of the phenylpropanoid
      pathway. These results provided evidence that up-regulation of genes involved in
      the phenylpropanoid pathway in response to the fungal elicitor resulted in
      enhanced metabolic responses associated with the protection in L. album. This
      approach can also be applied to improve lignan production.

PMID- 30109411
TI  - Untying the knot: protein quality control in inherited cardiomyopathies.
AB  - Mutations in genes encoding sarcomeric proteins are the most important causes of
      inherited cardiomyopathies, which are a major cause of mortality and morbidity
      worldwide. Although genetic screening procedures for early disease detection have
      been improved significantly, treatment to prevent or delay mutation-induced
      cardiac disease onset is lacking. Recent findings indicate that loss of protein
      quality control (PQC) is a central factor in the disease pathology leading to
      derailment of cellular protein homeostasis. Loss of PQC includes impairment of
      heat shock proteins, the ubiquitin-proteasome system, and autophagy. This may
      result in accumulation of misfolded and aggregation-prone mutant proteins, loss
      of sarcomeric and cytoskeletal proteins, and, ultimately, loss of cardiac
      function. PQC derailment can be a direct effect of the mutation-induced
      activation, a compensatory mechanism due to mutation-induced cellular dysfunction
      or a consequence of the simultaneous occurrence of the mutation and a secondary
      hit. In this review, we discuss recent mechanistic findings on the role of
      proteostasis derailment in inherited cardiomyopathies, with special focus on
      sarcomeric gene mutations and possible therapeutic applications.

PMID- 30109412
TI  - The effect of the broad-spectrum antibiotics for prevention of postoperative
      intra-abdominal abscess in pediatric acute appendicitis.
AB  - BACKGROUND: We investigated the efficacy of broad-spectrum antibiotics for
      prevention of postoperative intra-abdominal abscess in pediatric acute
      appendicitis with our 3 risk factors:-WBC > 16.5 (* 103/ul), CRP > 3.1 (mg/dl)
      and appendix maximum short diameter on diagnostic imaging > 11.4 mm. METHODS:
      Four hundred twenty-two patients were reviewed. Patients with 0-1 risk factors
      were assessed as low-risk and those with 2-3 were high-risk. In the low-risk
      group, Group A (n = 66) patients received broad-spectrum antibiotics and Group B
      patients (n = 265) received narrow-spectrum monotherapy. In the high-risk group,
      Group C patients (n = 63) received broad-spectrum antibiotics and Group D
      patients (n = 28), narrow-spectrum antibiotics. The outcomes were the incidence
      of postoperative abscess and the total duration of intravenous (IV) antibiotics.
      RESULTS: The incidence of intra-abdominal abscess was 6.06% in Group A versus
      1.89% in Group B (p = 0.08), and 19.05% in Group C versus 3.57% in Group D (p =
      0.06). Total IV antibiotic duration (days) were 6.12 +/- 2.87 in Group A versus
      3.83 +/- 0.69 in Group B (p < 0.01), and 7.84 +/- 4.57 in Group C versus 4.00 +/-
      0.82 in Group D (p < 0.01). CONCLUSION: Broad-spectrum antibiotics did not
      prevent postoperative intra-abdominal abscess in either low or high-risk groups.

PMID- 30109414
TI  - Osteochondral flap fracture of the coronoid in pediatric elbow dislocation: a
      case report and literature review.
AB  - Osteochondral flap fractures of the coronoid are rare occult fractures, often
      diagnosed in delay, in pediatric patients who underwent elbow dislocations. Only
      11 pediatric cases of osteochondral flap fractures of the coronoid are described
      in the literature. We describe a pediatric case treated in our institution for an
      elbow dislocation accompanied by a triad of elbow fractures, including the
      osteochondral flap fracture of the coronoid, and review available literature on
      the osteochondral flap fracture of the coronoid in pediatric patients.

PMID- 30109413
TI  - Neonates undergoing gastrointestinal surgery have a higher incidence of non-IgE
      mediated gastrointestinal food allergies.
AB  - PURPOSE: We aimed at investigating the incidence and risk factors of non-IgE
      mediated gastrointestinal food allergies (non-IgE-GI-FAs) in neonates and
      infants. METHODS: A total of 126 infants who underwent neonatal gastrointestinal
      surgeries were grouped into those with (n = 13) and those without an onset of non
      IgE-GI-FAs (n = 113). The characteristics of the two groups (e.g., birth weight,
      delivery type, small intestinal surgeries, and pre-/postoperative nutrition) were
      compared. Small intestinal surgeries were classified into those with and those
      without full-layer invasion of the small intestine. For the statistical analysis,
      postoperative nutrition was classified into breast milk only, formula milk, and
      elemental diet only. RESULTS: Except for full-layer surgical invasion of the
      small intestine and the period of parenteral nutrition, no significant
      differences were found between the two groups. Surgery with full-layer invasion
      was a risk factor of non-IgE-GI-FAs (odds ratio (OR) 10.70, 95% confidence
      interval (95% CI) 2.11-54.20; p = 0.004). Formula milk after surgery was a risk
      factor of non-IgE-GI-FAs when compared to breast milk (OR 5.65, 95% CI 1.33
      24.00; p = 0.019). CONCLUSION: Neonates undergoing gastrointestinal surgery have
      a higher incidence of non-IgE mediated gastrointestinal food allergies. We
      recommend that formula milk should not be administered to newborns who underwent
      neonatal gastrointestinal surgeries with full-layer invasion of the small
      intestine.

PMID- 30109415
TI  - Various factors affect erythrocyte blood transfusions in hip fracture patients.

PMID- 30109418
TI  - Development and validation of a web-based questionnaire to identify environmental
      risk factors for inflammatory bowel disease: the Groningen IBD Environmental
      Questionnaire (GIEQ).
AB  - BACKGROUND: In the complex etiology of inflammatory bowel disease (IBD), the
      exposome is a major contributor. Though many environmental exposures have been
      identified, quality of evidence varies greatly and overall evidence for the
      exposome is inconclusive. A universal, precise, and reproducible measurement tool
      is needed to study the exposome in IBD. METHODS: We built the web-based Groningen
      IBD Environmental Questionnaire (GIEQ), an extensive and structured questionnaire
      measuring potentially involved environmental exposures, consisting of 848 items,
      subdivided into 15 categories. For validation, 76 IBD patients completed the GIEQ
      twice (2-month interval). Cohen's kappa and correlation coefficients were used to
      compare both fills. Internal consistency was evaluated using Cronbach's alpha
      tests. Proportional bias was examined using Bland-Altman plots. RESULTS: In
      general, we obtained a mean kappa coefficient of 0.78 (standard deviation 0.17)
      for categorical questions and a mean intraclass correlation coefficient of 0.88
      (0.15) for numeric questions. Cronbach's alpha ranged from 0.64 to 1.0 with a
      mean of 0.79 (0.14). Bland-Altman plots showed proportional bias only for current
      physical activity score. CONCLUSIONS: The GIEQ is a reliable measurement tool to
      study the exposome in IBD, enabling consistent measurement of an extended number
      of environmental factors and their interactions. Use of the GIEQ across IBD
      cohorts will lead to more standardized, generalizable, and comparable results.
      Also, the GIEQ can be used for calculation of an exposome risk score, applicable
      for secondary prevention by identifying high-risk patients as well as to analyze
      interactions between the exposome and other aspects of IBD etiology.

PMID- 30109417
TI  - Toxoplasma gondii infection and behavioral outcomes in humans: a systematic
      review.
AB  - Studies suggest that the protozoan Toxoplasma gondii can disturb human behavior.
      This study aimed to systematically review the scientific literature on the
      possible associations between Toxoplasma gondii infection and neurobehavioral
      abnormalities in humans. We reviewed and summarized the studies published since
      1990. The descriptors used were related to T. gondii infection and behavioral
      outcomes in humans; the main databases of the medical literature were accessed.
      The results of eight original articles published between 1994 and 2016 were
      evaluated and described. The most common serological method was the enzyme
      immunoassay. Most of the researchers used validated instruments for behavioral
      evaluation. Seven studies reported some association between the prevalence of
      anti-T. gondii antibodies and some altered behavioral aspects in adult humans;
      these studies focused on adult population in Europe and the USA. The most
      reported behavioral deviations are related to greater impulsivity and
      aggressiveness. There are very few studies on this subject, which present some
      limitations for inference and conclusions: most were cross-sectional studies,
      with a small sample size and in similar populations. Investigations with a larger
      sample size of different population groups should be performed to evaluate
      multiple factors.

PMID- 30109419
TI  - Metabolic alterations associated with maternal undernutrition during the first
      half of gestation lead to a diabetogenic state in the rat.
AB  - BACKGROUND: Although recent studies have investigated the effect of maternal
      nutrition on metabolic programming of the offspring, the question whether a
      nutritional insult during early gestation favours an altered metabolic state of
      the mother that persists during the remainder period of pregnancy, when foetal
      growth is maximal, remains to be answered. METHODS: To address this issue, we
      analysed the effect of 40% food restriction during the first 12 days of gestation
      on glucose tolerance, as well as on liver and adipose tissue metabolism, in
      Sprague-Dawley pregnant rats. RESULTS: We found that undernutrition at early
      gestation blocks pregnancy-associated accumulation of fat, leading to a net
      breakdown of lipids that may account for an increased delivery of fatty acids and
      glycerol to the liver. Together with altered expression of hepatic enzymes, this
      creates a catabolic state, characterized by decreased lipogenesis and increased
      beta-oxidation, which contributes to the ketonemia of underfed mothers.
      Furthermore, we observed that undernutrition during early pregnancy impairs
      insulin sensitivity at this stage and, importantly, exacerbates insulin
      resistance at late gestation, contributing to a diabetogenic state. CONCLUSION:
      Undernutrition during the first half of pregnancy not only alters liver and
      adipose tissue metabolism, but also exacerbates the maternal insulin resistance
      at late gestation, which may increase their risk of gestational diabetes. GENERAL
      SIGNIFICANCE: Together, these findings highlight the persistent impact of
      maternal nutrition during early gestation on the metabolism of the mother during
      late pregnancy.

PMID- 30109416
TI  - A Leishmania-specific gene upregulated at the amastigote stage is crucial for
      parasite survival.
AB  - The morphological and biochemical alterations between the two life stages of
      Leishmania are governed by stage-regulated expression of several genes.
      Amastigote-specific genes are believed to have a role in the survival and
      replication of the parasite in the hostile environment of the mammalian host.
      Previously, we have reported the upregulated expression of A1 gene (LdA1) at the
      amastigote stage at RNA level. In the present study, we have further
      characterized LdA1, in order to understand its role in Leishmania. Sequence
      homology search revealed that LdA1 is unique to the Leishmania genus. Sequence-
      and structure-level functional annotations predicted the involvement of LdA1 in a
      range of biological processes critical for survival of the parasites. Western
      blot confirmed the upregulated expression of LdA1 at the protein level at the
      amastigote stage. Overexpression of LdA1 in Leishmania did not affect its growth,
      phenotype, or infectivity. Attempts to generate null mutants of LdA1 by
      homologous recombination were not successful. Repeated inability to create null
      mutants of LdA1 was suggestive of gene essentiality. Mutant parasites with a
      single allele deletion of LdA1 (LdA1+/-) showed reduction in motility, size, and
      growth rate at both the life stages in vitro, which was restored following gene
      add-back by episomal expression of LdA1 in mutant parasites. Although LdA1+/-
      parasites were able to infect macrophages ex vivo, their capacity to survive
      inside macrophages was reduced significantly (P < 0.01) beyond 72 h of infection.
      In conclusion, LdA1 is a Leishmania-specific gene having upregulated expression
      at the amastigote stage and is important for survival of Leishmania parasite.

PMID- 30109422
TI  - Vertebral artery dissection caused by atlantoaxial dislocation: a case report and
      review of literature.
AB  - BACKGROUND: Atlantoaxial dislocation (AAD) is the most common craniovertebral
      junction malformation (CVJm) which are anomalies of the bones and soft tissues
      surrounding the foramen magnum. It usually leads to neurologic abnormalities
      because of instability of this mobile area. But vertebral artery dissection (VAD)
      caused by AAD is uncommon. CASE REPORT: We report a 15-year-old boy who presented
      with acute onset of bilateral VAD leading to posterior circulation ischemic
      stroke (PCIS). Computed tomography angiography (CTA) indicated dissection and
      occlusion of bilateral intracranial vertebral arteries and AAD with os
      odontoideum. After antithrombotic treatment for 3 months, the patient got
      complete revascularization and received posterior C1-C2 fusion. DISCUSSION: There
      have only been tens of cases of PCIS caused by CVJm. We reviewed these relevant
      literatures and suggested that more attention should be paid to vascular
      impairment for patients with CVJm.

PMID- 30109421
TI  - Species-specific plant-soil feedbacks alter herbivore-induced gene expression and
      defense chemistry in Plantago lanceolata.
AB  - Plants actively interact with antagonists and beneficial organisms occurring in
      the above- and belowground domains of terrestrial ecosystems. In the past decade,
      studies have focused on the role of plant-soil feedbacks (PSF) in a broad range
      of ecological processes. However, PSF and its legacy effects on plant defense
      traits, such as induction of defense-related genes and production of defensive
      secondary metabolites, have not received much attention. Here, we study soil
      legacy effects created by twelve common grassland plant species on the induction
      of four defense-related genes, involved in jasmonic acid signaling, related to
      chewing herbivore defense (LOX2, PPO7), and in salicylic acid signaling, related
      to pathogen defense (PR1 and PR2) in Plantago lanceolata in response to
      aboveground herbivory by Mamestra brassicae. We also assessed soil legacy and
      herbivory effects on the production of terpenoid defense compounds (the iridoid
      glycosides aucubin and catalpol) in P. lanceolata. Our results show that both
      soil legacy and herbivory influence phenotypes of P. lanceolata in terms of
      induction of Pl PPO7 and Pl LOX2, whereas the expression of Pl PR1 and Pl PR2-1
      is not affected by soil legacies, nor by herbivory. We also find species-specific
      soil legacy effects on the production of aucubin. Moreover, P. lanceolata
      accumulates more catalpol when they are grown in soils conditioned by grass
      species. Our study highlights that PSF can influence aboveground plant-insect
      interactions through the impacts on plant defense traits and suggests that
      aboveground plant defense responses can be determined, at least partly, by plant
      specific legacy effects induced by belowground organisms.

PMID- 30109423
TI  - [Diseases of the schizophrenia spectrum disorder in old age : Diagnostic and
      therapeutic challenges].
AB  - BACKGROUND: The number of people with diseases of the schizophrenia spectrum in
      old age will increase significantly in the coming years. In the literature the
      topics of schizophrenia and delusional disorders in older and old people are
      inadequately represented. AIM: This article gives an overview of the most
      important diagnostic and differential diagnostic characteristics. Another
      important aspect is the pharmacological and non-pharmacological treatment options
      in old age. MATERIAL AND METHODS: The S3 guidelines of the German Association for
      Psychiatry, Psychotherapy and Psychosomatics (DGPPN) from 2006, the guidelines of
      the World Federation of Societies of Biological Psychiatry (WFSBP) from 2012,
      2013, 2015 and the consensus statement of the Austrian Association for Neuro
      Psychopharmacology and Biological Psychiatry (OGPB) from 2016 formed the basic
      literature for this review. In addition, a targeted search in the databases
      PubMed, PubPsych and Cochrane Library as well as in German Journals, such as
      DerNervenarzt, Neuropsychiatrie, Psychiatrische Praxis and Zeitschrift fur
      Gerontologie und Geriatrie concerning the keywords schizophrenia, delusional
      disorder, diagnostics, therapy and older people was carried out. RESULTS: Besides
      aspects on epidemiology, clinical manifestation, diagnostics, differential
      diagnostics and course of the illness, pharmacological and non-pharmacological
      treatment options are presented. CONCLUSION/DISCUSSION: In clinical practice a
      clear diagnostic assignment is often a challenge in older and very old people
      with psychotic symptoms, The necessary pharmacological treatment is available but
      is limited by tolerability, comorbidities and polypharmacy. Non-pharmacological
      treatment options have hardly been investigated.

PMID- 30109425
TI  - Be careful of the masquerades: differentiating secondary myelodysplasia from
      myelodysplastic syndromes in clinical practice.
AB  - In patients suspected to have myelodysplastic syndrome (MDS), especially in those
      patients without cytogenetic abnormalities or blast excess, accurate morphologic
      review by an expert hematopathologist and meticulous exclusion of other secondary
      causes of myelodysplasia are vital to establish the diagnosis. Errors in
      diagnosis can lead to dangerous consequences such as the administration of
      hypomethylating agents, lenalidomide, or even the use of intensive chemotherapy
      or allogeneic hematopoietic cell transplantation in patients who do not have an
      underlying MDS or even a malignant hematopoietic process. Additionally, beyond
      the possible harm and lack of efficacy of such therapies if the diagnosis of MDS
      is erroneous, the secondary myelodysplasia and resultant cytopenias are not
      likely to resolve unless the underlying etiology is identified and addressed.
      Discriminating a malignant process such as MDS from non-malignant secondary
      myelodysplasia can be quite challenging, and community hematologists/oncologists
      should consider referral to specialized physicians (both clinical experts and
      experienced hematopathologists) if there is any doubt regarding the diagnosis. In
      this article, we present a representative case series of patients from our own
      practice who posed diagnostic dilemmas and propose a systematic approach for
      assessment for secondary causes of myelodysplasia.

PMID- 30109424
TI  - Transient adrenal insufficiency in diffuse large B cell lymphoma patients after
      chemotherapy with short-course, high-dose corticosteroids.
AB  - Data on the rate of adrenal insufficiency (AI) in patients receiving short-course
      and high-dose corticosteroids are limited. In this study, we aimed to determine
      the incidence of AI in newly diagnosed, diffuse large B cell lymphoma (DLBCL)
      patients after receiving rituximab, cyclophosphamide, doxorubicin, vincristine,
      and prednisone [or prednisolone] (R-CHOP/CHOP) regimen. We enrolled newly
      diagnosed DLBCL patients who were scheduled to receive 6-8 cycles of R-CHOP/CHOP
      regimen. One-microgram adrenocorticotropic hormone (ACTH) stimulation tests were
      performed at the study entry and 3 weeks after each cycle of chemotherapy (CMT).
      AI was defined by a peak-stimulated serum cortisol of less than 18 MUg/dL. For
      patients who had AI after completing a course of CMT, 1-MUg ACTH stimulation
      tests were carried out at 60 and 90 days after the last CMT cycle to assess the
      duration of hypothalamic-pituitary-adrenal (HPA) axis recovery. Ten DLBCL
      patients were included in this study, with a total of 84 1-MUg ACTH stimulation
      tests. Their mean age was 52 years. AI occurred in 3 out of the 10 patients
      (30%). The first occurrence of AI was after the third CMT cycle, and the
      incidence was highest after the fifth cycle. Adrenal function recovered
      completely 3 to 5 weeks after completing the course of CMT, except for 1 patient,
      whose HPA axis suppression persisted 90 days after the last CMT cycle. Receiver
      operating characteristic (ROC) analysis revealed that a basal cortisol level of <
      8.7 MUg/dL was predictive of AI, with a sensitivity and specificity of 80% and
      72.2%, respectively. Transient HPA axis suppression can occur in DLBCL patients
      receiving R-CHOP/CHOP regimen. We strongly encourage careful observation and
      examination for potential adrenal insufficiency in such patients, particularly
      after the fifth cycle of chemotherapy.

PMID- 30109427
TI  - ?

PMID- 30109426
TI  - [Panuveitis of infectious genesis].
AB  - In a patient with sub-acute loss of vision a panuveitis with papillitis and
      chorioretinitis was diagnosed within an initial diagnosis of lues and human
      immunodeficiency virus (HIV). Epidemiological data show an increasing incidence
      of HIV and lues infections in recent years. Therefore, ophthalmologists need to
      bear an infectious etiology of inflammation of the eye in mind.

PMID- 30109429
TI  - Do 3D-calculated volume distribution of a stone in pelvicalyceal system affect
      complications of percutaneous nephrolithotomy?
AB  - In our study, we examined the effect of the three-dimensional (3D) stone
      segmentation volume and its ratio to the renal collecting system on complication
      rates. Data from141 patients who underwent PCNL surgery were analyzed
      retrospectively. Volume segmentation of both the renal collecting system and
      stones was obtained from 3D segmentation software with the images on CT data.
      After creation of a 3D surface volume rendering of renal stones and the
      collecting system, segmentation of the renal collecting system volume (RCSV) and
      analyzed stone volume (ASV) was analyzed and the ASV-to-RCSV ratio was
      calculated. Univariate analysis and multivariate logistic regression model were
      used to determine factors that affected complication status. Diagnostic value for
      the prediction of complication rates was analyzed using receiver operating
      characteristic (ROC) incline. Overall, there were 141 (92 male and 49 female)
      eligible patients included in the current study. The overall complication rate
      for PCNL monotherapy was 31.9%. Multivariate regression analysis (forward
      stepwise) revealed that the ASV-to-RCSV ratio and number of tracts were
      independent risk factors for developing complications (OR 1.17, p < 0.001; OR
      7.87, p = 0.002; respectively). The ROC analysis revealed a cut-off value of
      16.23% (AUC 0.869, p < 0.001, sensitivity 93.3%, specificity 78.1%) for the ASV
      to-RCSV ratio. The distribution of stone burden volume in the pelvicalyceal
      system, which is calculated as a numerical value using the 3D volume segmentation
      method, is an important predictor of the complication rate before PCNL. The ASV
      to-RCSV ratio as a quantitative value may be an instrument for urologists before
      surgery to help preoperative planning.

PMID- 30109430
TI  - Physico-chemical parameters and levels of polycyclic aromatic hydrocarbons in
      water, sediments and soil in River Nzoia, Kakamega county-Kenya.
AB  - The River Nzoia basin is the main source of water for domestic, agricultural, and
      industrial activities. The levels of the priority polycyclic aromatic
      hydrocarbons (PAHs) in water, soil, and sediments of River Nzoia during two
      seasons are reported. The physico-chemical parameters gave levels that were
      within the maximum allowable limit but with significant differences between the
      wet and dry seasons (p < 0.005). In water (max: 0.092 +/- 0.003 ng/L) and soils
      (max 9.74 +/- 1.97 ng/g), levels were significantly higher in the wet season
      unlike in sediment (8.94 +/- 3.33 ng/g). Although all levels were below the
      recommended limits, the results form a need basis for continuous monitoring as
      recommended by WHO and USEPA.

PMID- 30109428
TI  - Essential Gene Clusters Identified in Stenotrophomonas MB339 for Multiple
      Metal/Antibiotic Resistance and Xenobiotic Degradation.
AB  - Stenotrophomonas MB339, a bacterium, which could potentially utilize aromatic
      compounds and tolerate different heavy metals was isolated from industrial
      wastewater. Subsequent experiments revealed strains ability to resist antibiotics
      ofloxacin, streptomycin, rifampicillin, erythromycin, ampicillin, clindamycin,
      and toxicants including As2+, Hg2+, Cu2+, Ni2+, Pb2+. The shotgun sequencing
      strategy, genome assembly and annotation uncovered specific features, which make
      this strain MB339 effectively promising to cope with highly contaminated
      conditions. This report presents isolate's assembled genome and its functional
      annotation identifying a set of protein coding genes (4711), tRNA (69 genes), and
      rRNA (9 genes). More than 2900 genes were assigned to various Clusters of
      Orthologous Groups (COGs) and 1114 genes attributed to 37 different Koyoto
      Encyclopedia of Genes and Genomes (KEGGs) pathways. Among these annotated genes,
      eighteen were for key enzymes taking part in xenobiotic degradation. Furthermore,
      149 genes have been assigned to virulence, disease, and defense mechanisms
      responsible for multidrug and metal resistance including mercury, copper, and
      arsenic operons. These determinants comprised genes for membrane proteins, efflux
      pumps, and metal reductases, suggesting its potential applications in
      bioremediation.

PMID- 30109431
TI  - Aggression and its association with suicidality in migraine patients: a case
      control study.
AB  - BACKGROUND: To identify aggression and its association with suicidality in
      migraine patients. METHODS: We enrolled 144 migraine patients who made their
      first visit to our headache clinic. We collected data regarding their clinical
      characteristics and the patients completes the Aggression Questionnaire (AQ) and
      other questionnaires. We also interviewed patients with the Mini International
      Neuropsychiatric Interview-Plus Version 5.0.0 (MINI) to identify their
      suicidality. The degree of aggression in migraine patients was compared to the
      degree of aggression in healthy controls. Major determinants for aggression and
      its association with suicidality were also examined. RESULTS: The overall AQ
      score and anger and hostility subscale scores were higher in migraine patients
      than controls. For migraine chronicity, patients with chronic migraine (CM) had a
      higher overall AQ score and physical aggression, anger, and hostility subscale
      scores than controls. On the other hand, all AQ scores in patients with episodic
      migraine were not different from the scores of the controls. Although several
      factors were associated with the overall AQ score, major determinants were
      anxiety (beta = 0.395, p < 0.001), headache intensity (beta = 0.180, p = 0.016),
      and CM (beta = - 0.165, p = 0.037). Patients who had suicidality based on the
      MINI showed a higher overall AQ score than patients without suicidality (p <
      0.001). CONCLUSIONS: Aggression is likely to be a common feature in CM. Comorbid
      aggression may help to identify suicidality in migraine patients.

PMID- 30109432
TI  - Dysmobility syndrome is associated with prevalent morphometric vertebral fracture
      in older adults: the Korean Urban-Rural Elderly (KURE) study.
AB  - : In a community-dwelling elderly cohort, dysmobility syndrome was associated
      with elevated odds of morphometric vertebral fracture or any prevalent fracture,
      independent of age and covariates. Dysmobility syndrome improved discrimination
      for fracture when added to the FRAX score. INTRODUCTION: Dysmobility syndrome was
      coined to indicate patients with impaired musculoskeletal health. Data on the
      association of dysmobility syndrome with prevalent morphometric vertebral
      fracture (VF) in elderly persons are limited. METHODS: A total of 1369 community
      dwelling elderly subjects (mean age 71.6 years; women 66%) were analyzed.
      Dysmobility syndrome was defined as >= 3 components among falls, low lean mass,
      high fat mass, osteoporosis, low grip strength, and low timed get-up-and-go
      performance. VF was defined as a >= 25% reduction in the height of vertebral
      bodies in plain radiographs. Modified cutpoints of each component at which
      elevate the odds of fracture were investigated using receiver-operating
      characteristics analysis. Net reclassification improvement (NRI) and integrated
      discrimination index (IDI) were calculated to assess additive discriminatory
      value of dysmobility syndrome over FRAX. RESULTS: The prevalence of VF and any
      fracture composite of VF and non-VF was 16% and 25%, respectively, increasing
      according to number of dysmobility components (from 0 to 5; VF 10-35%; any
      fracture 16-45%). Dysmobility syndrome was associated with elevated odds of VF
      (adjusted OR [aOR] 1.52, 95% CI 1.08-2.15) or any fracture (aOR 1.46, 95% CI 1.07
      1.98) but no longer with non-VF (aOR 1.31, 95% CI 0.86-1.98) in multivariate
      model, whereas modified definition showed robust association with non-VF (aOR
      1.79, 95% CI 1.23-2.60). Dysmobility syndrome improved discrimination for
      prevalent fracture when added to FRAX (NRI 0.25, 95% CI 0.13-0.37; IDI 0.020, 95%
      CI 0.014-0.026). CONCLUSIONS: Dysmobility syndrome was associated with elevated
      odds of morphometric VF in community-dwelling older adults, independent of age
      and covariates.

PMID- 30109433
TI  - Mineralocorticoids and Cardiovascular Disease in Females with Insulin Resistance
      and Obesity.
AB  - PURPOSE OF THE REVIEW: In the present review, we will discuss the evidence and
      the mechanisms underlying the complex interplay between obesity,
      mineralocorticoid receptor activation, and cardiovascular dysfunction with
      special emphasis on the pathogenesis of cardiovascular disease (CVD) in obese and
      insulin-resistant females. RECENT FINDINGS: Since the initial isolation of
      aldosterone in 1953 and the cloning of the mineralocorticoid receptor (MR)
      decades later, our understanding has expanded tremendously regarding their
      involvement in the pathogenesis of CVD. Recent results from both pre-clinical and
      clinical studies support a close correlation between increase adiposity and
      enhanced aldosterone production (MR activation). Importantly, insulin resistance
      and obese females are more prone to the deleterious cardiovascular effects of MR
      activation, and enhanced MR activation in females has emerged as an important
      causative event in the genesis of a more severe CVD in diabetic women. Different
      clinical trials have been completed examining the effect of MR blockade in
      subjects with CVD. Despite its important beneficial mortality impact, side
      effects are frequent and a newer MR antagonist, finerenone, with less risk of
      hyperkalemia is currently being tested in large clinical trials.

PMID- 30109434
TI  - Evaluation of thermal indices for their applicability in obstacle-resolving
      meteorology models.
AB  - A thermally comfortable design of outdoor spaces favors social interaction and
      outdoor activities and thus contributes to the overall well-being of urban
      dwellers. To assess such a design, obstacle-resolving models (ORM) combined with
      thermal indices may be used. This paper reviews existing thermal indices to
      identify those suitable for thermal comfort assessment with ORMs. For the
      identification, 11 criteria and six index features are derived from literature
      analysis focusing on the characteristics of human environmental heat exchange, of
      outdoor urban environments, and of ORMs. An air temperature weighted world
      population distribution is calculated to derive the minimal air temperature
      range; a thermal index should cover to be applicable to 95% of the world
      population. The criteria are applied to 165 thermal indices by reviewing their
      original publications. Results show that only four thermal indices are suitable
      to be applied globally in their current form to various outdoor urban
      environments and also fulfill the requirements of ORMs. The evaluation of the
      index features shows that they differ with respect to the comprehensiveness of
      the thermophysiological model, the assessed human response, the treatment of
      clothing and activity, and the computational costs. Furthermore, they differ in
      their total application frequency in past ORM studies and in their application
      frequency for different climatic zones, as a systematic literature analysis of
      thermal comfort studies employing ORMs showed. By depicting the differences of
      the thermal indices, this paper provides guidance to select an appropriate
      thermal index for thermal comfort studies with ORMs.

PMID- 30109435
TI  - P2Rank: machine learning based tool for rapid and accurate prediction of ligand
      binding sites from protein structure.
AB  - BACKGROUND: Ligand binding site prediction from protein structure has many
      applications related to elucidation of protein function and structure based drug
      discovery. It often represents only one step of many in complex computational
      drug design efforts. Although many methods have been published to date, only few
      of them are suitable for use in automated pipelines or for processing large
      datasets. These use cases require stability and speed, which disqualifies many of
      the recently introduced tools that are either template based or available only as
      web servers. RESULTS: We present P2Rank, a stand-alone template-free tool for
      prediction of ligand binding sites based on machine learning. It is based on
      prediction of ligandability of local chemical neighbourhoods that are centered on
      points placed on the solvent accessible surface of a protein. We show that P2Rank
      outperforms several existing tools, which include two widely used stand-alone
      tools (Fpocket, SiteHound), a comprehensive consensus based tool (MetaPocket
      2.0), and a recent deep learning based method (DeepSite). P2Rank belongs to the
      fastest available tools (requires under 1 s for prediction on one protein), with
      additional advantage of multi-threaded implementation. CONCLUSIONS: P2Rank is a
      new open source software package for ligand binding site prediction from protein
      structure. It is available as a user-friendly stand-alone command line program
      and a Java library. P2Rank has a lightweight installation and does not depend on
      other bioinformatics tools or large structural or sequence databases. Thanks to
      its speed and ability to make fully automated predictions, it is particularly
      well suited for processing large datasets or as a component of scalable
      structural bioinformatics pipelines.

PMID- 30109436
TI  - What role does metal allergy sensitization play in total knee arthroplasty
      revision?
AB  - BACKGROUND: Clinicians are often faced with the decision whether to revise a
      painful total knee replacement in patients who have chronic vague pain with no
      apparent explanation. A sensitive metal testing assay called the lymphocyte
      stimulation test has been used to detect nickel sensitization in patients with
      orthopedic implants. We hypothesize that nickel sensitization plays a role in the
      pathology of failed joint arthroplasty in patients with unexplained
      dissatisfaction. METHODS: 32 patients with symptomatic total knee arthroplasty
      without obvious mechanical findings were tested prior to revision surgery. 19
      nickel-sensitized and 13 non-sensitized patients were compared by cell counts of
      synovium surgical specimens for CD4+ and CD8+ cell lines. Patients were then
      revised with ceramic-coated implants. Secondary evaluation of functional
      outcomes, range of motion, and pain relief were assessed. RESULTS: Nickel
      sensitive patients showed a statistical increase in CD4+ reactivity compared to
      CD8+ reactivity. The ratio of CD4+/CD8+ T lymphocytes was 1.28 in nickel
      sensitive patients versus 0.76 in the control (p = 0.009). There was no
      difference in functional scores, clinical scores, or range of motion after
      revision. CONCLUSIONS: This study provides objective data via histological
      analysis in support of a nickel allergic sensitization in failed arthroplasties
      where clinical and/or radiographic abnormalities may not be apparent. Biopsy for
      CD4+/CD8+ cell counts may provide further proof of the existence of nickel
      sensitization in lymphocyte stimulation test positive patients, and more
      importantly, may implore the surgeon to consider low nickel implant design in
      these patients.

PMID- 30109437
TI  - Latest clinical recommendations on valproate use for migraine prophylaxis in
      women of childbearing age: overview from European Medicines Agency and European
      Headache Federation.
AB  - Migraine is a common and burdensome neurological condition which affects mainly
      female patients during their childbearing years. Valproate has been widely used
      for the prophylaxis of migraine attacks and is also included in the main European
      Guidelines. Previous (2014) European recommendations on limiting the use of
      valproate in women of childbearing age did not achieve their objective in terms
      of limiting the use of valproate in women of childbearing age and raising
      awareness regarding the hazardous effect of valproate to children exposed in
      utero. The teratogenic and foetotoxic effects of valproate are well documented,
      and more recent studies show that there is an even greater neurodevelopmental
      risk to children exposed to valproate in the womb. The latest 2018 European
      review from the European Medicines Agency, with the active participation of the
      European Headache Federation, concluded that not enough has been done to mitigate
      the risks associated with in utero exposure to valproate. The review called for
      more extensive restrictions to the conditions for prescribing, better public
      awareness, and a more effective education campaign in migrainous women.

PMID- 30109438
TI  - Fremanezumab blocks CGRP induced dilatation in human cerebral, middle meningeal
      and abdominal arteries.
AB  - BACKGROUND: Fremanezumab (TEV-48125) is a fully humanized anti-calcitonin gene
      related peptide (CGRP) monoclonal antibody (mAb) that has shown positive results
      in the prevention of episodic migraine and chronic migraine. Previous preclinical
      studies have revealed CGRP antagonistic effects on intracranial arteries (ICA).
      The aim of the study was to evaluate the in vitro antagonistic effects of
      fremanezumab on human arteries. METHODS: Arteries were removed in conjunction
      with neurosurgery (cerebral, CA, and middle meningeal artery, MMA, n = 7) or
      reconstructive abdominal surgery (abdominal artery, AA, n = 6). Ring segments of
      the vessels were mounted in a sensitive myograph, the functional responses of
      vasoactive intestinal peptide (VIP), substance P and CGRP in increasing
      concentrations (10- 10-10- 7 M) were studied using pre-contraction with 30 mM
      potassium chloride (KCl). The concentrations of fremanezumab or isotype control
      antibody (66.7 nM, 0.33 MUM, 0.67 MUM) were given 30 min prior to CGRP
      administration. RESULTS: All included arteries responded with a strong stable
      contraction to the application of 30 mM KCl. During this pre-contraction, CGRP
      caused a concentration-dependent relaxation which differed slightly in maximum
      effect (Imax) between the types of arteries (ICA = 100%; AA 80%). Fremanezumab
      (66.7 nM) showed a shift in the IC50 value of CGRP, but no significant change in
      Imax. At higher doses there was also a reduction of Imax. For AA, the Imax
      decreased from 71% at 66.7 nM, to 4.5% with 0.33 MUM of fremanezumab. Isotype
      control antibody did not modify the responses. There was no effect on
      concentration-dependent relaxation with VIP with 66.7 nM of fremanezumab or
      isotype control. CONCLUSION: CGRP relaxes pre-contracted human arteries by 80
      100%, but with different IC50; the potency range was ICA < AA. The antagonistic
      effect and potency of fremanezumab was similar, suggesting that there are
      vasodilatory CGRP receptors present in all studied arteries and that the antibody
      may have effect in all studied vessels.

PMID- 30109439
TI  - Characteristics of air quality and sources affecting high levels of PM10 and
      PM2.5 in Poland, Upper Silesia urban area.
AB  - The reports concerning air quality published by WHO and EEA showed that 33 out of
      50 cities with highest concentration of particulate matter (PM)2.5 in UE are
      located in Poland. Various investigations identify main health outcomes to be
      consistently related to PM10 and PM2.5. Increased concentration of PM is
      responsible for 47.3 thousands of premature deaths every year in Poland. The
      objective of this study was the measurement-based assessment for determining
      whether the concentrations of PM10 and PM2.5 are within admissible limits or
      exceeded in Silesia Province. The data provided by the Voivodship Inspectorate
      for Environmental Protection in Katowice was used in the analysis. The
      measurements were made in years 2009-2016 for PM2.5 and 2014-2017 for PM10 in
      three measurement stations: two in Katowice (capital of Silesia Province) and one
      in Zory. The increase in the number of excessive levels of average daily PM10
      concentration in year 2017 were observed in all three measurement stations, both
      for the acceptable level, information and alarm level, with lack or singular
      excessive levels in the previous years. The increase in average annual PM2.5
      concentrations in year 2016 was also observed, as compared to the previous year
      in all three measurement stations. The highest pollution is observed in winter.
      The main cause of exceeded acceptable PM concentrations in Poland is household
      heating systems, boilers and furnaces burnt with coal or wood, and chimneys. In
      Silesian Province, the air quality is poor and has deteriorated over the last
      year.

PMID- 30109441
TI  - High-temperature superconductivity as viewed from the maximum hardness principle.
AB  - The Maximum Hardness Principle - and its reformulation by Chattaraj as the
      Minimum Polarizability Principle - is an immensely useful concept which works in
      support of a chemical intuition. As we show here, it may also be used to
      rationalize the scarcity of high-temperature superconductors, which stems - inter
      alia - from rarity of high-density of state metals in Nature. It is suggested
      that the high-temperature oxocuprate superconductors as well as their iron
      analogues - are energetically metastable at T ? 0 K and p ? 0 atm conditions, and
      their tendency for disproportionation is hindered only by the substantial
      rigidity of the crystal lattice, while the phase separation and/or superstructure
      formation is frequently observed in these systems. This hypothesis is
      corroborated by hybrid density functional theory theoretical calculations for Na-
      (thus: hole) or La- (thus: electron) doped CaCu(II)O2 precursor. Non-equilibrium
      synthetic methods are suggested to be necessary for fabrication of high
      temperature superconductors of any sort. Graphical abstract Doped oxocuprate
      superconductors are shown to be unstable with respect to phase separation
      (disproportionation) in accordance with the Maximum Hardness Principle; their
      metastability is mostly due to rigidity of [CuO2] sheets and preparation using
      high-temperature conditions.

PMID- 30109443
TI  - An 18-month clinical evaluation of three different universal adhesives used with
      a universal flowable composite resin in the restoration of non-carious cervical
      lesions.
AB  - OBJECTIVE: The aim of this randomized, controlled prospective clinical trial was
      to evaluate and compare the performances of three different universal adhesives
      using a flowable universal composite resin in the restoration of non-carious
      cervical lesions (NCCLs) over an 18-month period. MATERIALS AND METHODS: Eighteen
      participants recieved 99 restorations from a single operator. NCCLs were divided
      into three groups according to adhesive systems used: Clearfil Universal Bond
      (CU), iBOND Universal (IU), and G-Premio Bond (GP). No enamel bevel was placed
      and no mechanical retention was created for the NCCLs. Prior to adhesive
      procedures, selective etching was performed with 37% phosphoric acid. Adhesive
      systems were applied following manufacturers' instructions and the lesions were
      restored with a flowable composite resin (G-aenial Universal Flo). Restorations
      were finished and polished immediately after placement and scored with regard to
      retention, marginal discoloration, marginal adaptation, sensitivity, surface
      texture, and color match using modified USPHS criteria after a week (baseline)
      and 6, 12, and 18 months. Descriptive statistics were performed using chi-square
      tests. RESULTS: The 18-month recall rate was 88.8% and retention rates for CU,
      IU, and GP were 100%, 96.8%, and 100%, respectively. No restorations exhibited
      post-operative sensitivity and secondary caries. After 18 months, CU, IU, and GP
      groups showed similar alpha rates for marginal adaptation (CU 93.1%, IU 90%, GP
      81.8%) and marginal discoloration (CU 100%, IU 90%, GP 87.9%). A total of ten (CU
      2, IU 3, GP 5) restorations exhibited bravo scores for surface texture and three
      (CU 2, GP 1) restorations showed bravo score for color match. No statistical
      differences were found among the tested adhesives for any criteria evaluated (p >
      0.05). CONCLUSION: The three adhesive systems demonstrated similar performances
      during the 18-month follow-up in the restoration of NCCLs. CLINICAL RELEVANCE:
      Universal adhesives could be used successfully in the restoration of NCCLs.

PMID- 30109440
TI  - In silico identification of inhibitors against Plasmodium falciparum histone
      deacetylase 1 (PfHDAC-1).
AB  - In erythrocytes, actively multiplying Plasmodium falciparum parasites exhibit a
      unique signature of virulence associated histone modifications, thereby
      epigenetically regulating the expression of the majority of genes. Histone
      acetylation is one such modification, effectuated and maintained by the dynamic
      interplay of two functionally antagonist enzymes, histone acetyltransferases
      (HATs) and histone deacetylases (HDACs). Their inhibition leads to
      hypo/hyperacetylation and is known to be deleterious for P. falciparum, and hence
      they have become attractive molecular targets to design novel antimalarials. Many
      compounds, including four Food and Drug Administration (FDA) approved drugs, have
      been developed so far to inhibit HDAC activity but are not suitable to treat
      malaria as they lack selectivity and cause cytotoxicity in mammalian cells. In
      this study, we used comparative modeling and molecular docking to establish
      different binding modes of nonselective and selective compounds in the PfHDAC-1
      (a class I HDAC protein in P. falciparum) active site and identified the
      involvement of active site nonidentical residues in binding of selective
      compounds. Further, we have applied virtual screening with precise selection
      criteria and molecular dynamics simulation to identify novel potential inhibitors
      against PfHDAC-1. We report 20 compounds (10 from ChEMBL and 10 from analogues
      compound library) bearing seven scaffolds having better affinity toward PfHDAC-1.
      Sixteen of these compounds are known antimalarials with 14 having activity in the
      nanomolar range against various drug resistant and sensitive strains of P.
      falciparum. The cytotoxicity of these compounds against various human cell lines
      are reported at relatively higher concentration and hence can be used as
      potential PfHDAC-1 inhibitors in P. falciparum. These findings indeed show great
      potential for using the above molecules as prospective antimalarials.

PMID- 30109442
TI  - Nephrotoxicity and Kidney Transport Assessment on 3D Perfused Proximal Tubules.
AB  - Proximal tubules in the kidney play a crucial role in reabsorbing and eliminating
      substrates from the body into the urine, leading to high local concentrations of
      xenobiotics. This makes the proximal tubule a major target for drug toxicity that
      needs to be evaluated during the drug development process. Here, we describe an
      advanced in vitro model consisting of fully polarized renal proximal tubular
      epithelial cells cultured in a microfluidic system. Up to 40 leak-tight tubules
      were cultured on this platform that provides access to the basolateral as well as
      the apical side of the epithelial cells. Exposure to the nephrotoxicant cisplatin
      caused a dose-dependent disruption of the epithelial barrier, a decrease in
      viability, an increase in effluent LDH activity, and changes in expression of
      tight-junction marker zona-occludence 1, actin, and DNA-damage marker H2A.X, as
      detected by immunostaining. Activity and inhibition of the efflux pumps P
      glycoprotein (P-gp) and multidrug resistance protein (MRP) were demonstrated
      using fluorescence-based transporter assays. In addition, the transepithelial
      transport function from the basolateral to the apical side of the proximal tubule
      was studied. The apparent permeability of the fluorescent P-gp substrate
      rhodamine 123 was decreased by 35% by co-incubation with cyclosporin A.
      Furthermore, the activity of the glucose transporter SGLT2 was demonstrated using
      the fluorescent glucose analog 6-NBDG which was sensitive to inhibition by
      phlorizin. Our results demonstrate that we developed a functional 3D perfused
      proximal tubule model with advanced renal epithelial characteristics that can be
      used for drug screening studies.

PMID- 30109445
TI  - Extra-renal manifestations of atypical hemolytic uremic syndrome.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a rare and complex disease resulting
      from abnormal alternative complement activation with a wide range of clinical
      presentations. Extra-renal manifestations of aHUS can involve many organ systems,
      including the peripheral and central nervous, gastrointestinal, cardiovascular,
      integumentary, pulmonary, as well as the eye. While some of these extra-renal
      manifestations occur in the acute phase of aHUS, some can also occur as long-term
      sequelae of unopposed complement activation. Extra-renal symptoms are observed in
      approximately 20% of patients with aHUS, with the incidence of specific organ
      system complications ranging from a few case reports to 50% of described
      patients. Careful monitoring for extra-renal involvement is critical in patients
      with aHUS, as prompt evaluation and management may decrease the risk of high
      morbidity and mortality associated with aHUS.

PMID- 30109446
TI  - Writing a paper for publication.

PMID- 30109444
TI  - Surviving in hot and cold: psychrophiles and thermophiles from Deception Island
      volcano, Antarctica.
AB  - Polar volcanoes harbor unique conditions of extreme temperature gradients capable
      of selecting different types of extremophiles. Deception Island is a marine
      stratovolcano located at Maritime Antarctica that is notable for its pronounced
      temperature gradients over very short distances, reaching values up to 100 
      degrees C in the fumaroles, and subzero temperatures next to the glaciers. Due to
      these characteristics, Deception can be considered an interesting analogue of
      extraterrestrial environments. Our main goal in this study was to isolate
      thermophilic and psychrophilic bacteria from sediments associated with fumaroles
      and glaciers from two geothermal sites in Deception Island, comprising
      temperatures between 0 and 98  degrees C, and to evaluate their survivability to
      desiccation and UV-C radiation. Our results revealed that culturable thermophiles
      and psychrophiles were recovered among the extreme temperature gradient in
      Deception volcano, which indicates that these extremophiles remain alive even
      when the conditions do not comprise their growth range. The viability of
      culturable psychrophiles in hyperthermophilic environments is still poorly
      understood and our work showed the importance of future studies about their
      survival strategies in high temperatures. Finally, the spore-forming thermophilic
      isolates which we found have displayed good survival to desiccation and UV-C
      irradiation, which suggests their potential to be further explored in
      astrobiological studies.

PMID- 30109447
TI  - Effect of different rituximab regimens on B cell depletion and time to relapse in
      children with steroid-dependent nephrotic syndrome.
AB  - BACKGROUND: Several studies have demonstrated that rituximab (RTX) improves
      relapse-free survival in patients with steroid-dependent nephrotic syndrome
      (SDNS). However, these studies used various RTX regimens and there are few data
      comparing these regimens in children with SDNS. In this retrospective study, we
      assessed the effect of three different initial RTX regimens on both time to B
      cell reconstitution and to first relapse. METHODS: Sixty-one SDNS patients
      receiving a first course of RTX were included. Group 1 received one injection of
      100 mg/m2, group 2 received one injection of 375 mg/m2, and group 3 received two
      injections of 375 mg/m2 at day 0 and day 7. Time to B cell reconstitution and
      time to first relapse and respective risk factors were studied. RESULTS: Median
      time to B cell reconstitution was 2.5 [1.8-3.5], 5.0 [3.9-6.0], and 6.6 [4.6-7.8]
      months in groups 1, 2, and 3, respectively. RTX regimen was associated with time
      to B cell reconstitution (HRs group 2 vs. 3, 4.07 [1.96-8.48]; group 1 vs. 3,
      11.13 [4.04-30.67]). One-year relapse-free survival was 50% [58-77], 59% [42-76],
      and 72% [46-87] in groups 1, 2, and 3, respectively. RTX regimen was associated
      with risk of relapse (HRs group 2 vs. 3, 1.55 [0.51-4.65]; group 1 vs. 3, 4.98
      [1.15-21.60]). CONCLUSIONS: The initial dose of rituximab impacts time to B cell
      reconstitution and the probability of relapse. Risk of relapse is also associated
      with patient characteristics, suggesting that RTX regimen could be modified for
      each patient to balance efficacy, cost, and side effects.

PMID- 30109448
TI  - Age- and sex-dependent variation in the activity of antioxidant enzymes in the
      brown trout (Salmo trutta).
AB  - Oxidative stress is defined as the imbalance between pro-oxidant and antioxidant
      molecules in favor of the former and it represents one of the main driving forces
      of aging. To counteract the harmful effects of oxidative stress, organisms
      evolved a complex antioxidant system. According to the free radical theory of
      aging, while the production of reactive oxygen species (ROS) increases with age,
      the antioxidant defenses decline. Although this relationship has been
      investigated in diverse vertebrate taxa, the information in fish is scant and
      inconsistent, particularly for wild populations. Thus, the aim of the present
      study was the investigation of age- and sex-related changes of the antioxidant
      enzymes activity in free-living individuals of the brown trout (Salmo trutta). We
      measured the activity of the main enzymes involved in antioxidant protection,
      namely superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),
      and glutathione S-transferase (GST), as well as lipid peroxidation, in the gills
      and the liver dissected from brown trout (1+- to 5+-year-old). A significant age
      dependent variation in the activity of antioxidant enzymes was noted, with the
      exception of CAT. GPx activity followed a significant increasing trend with age
      in both the organs, while SOD decreased in the liver. Increased GST activity was
      found in the gills only. Lipid peroxidation levels significantly decreased with
      age in both the organs. SOD and CAT showed sex-dependent differences in the liver
      of brown trout, with males showing lower enzymatic activity than females. Our
      data contribute to improve the knowledge on the relationship between antioxidant
      enzyme activity, aging, and sex in fish.

PMID- 30109449
TI  - Maternal care, larviparous and oviparous reproduction of Hypoaspis larvicolus
      (Acari: Laelapidae) feeding on astigmatid mites.
AB  - Hypoaspis larvicolus (Acari: Laelapidae) (first report from Turkey) occurred
      together with Sancassania polyphyllae (Acari: Acaridae) on the larvae of the
      scarab beetle, Polyphylla fullo (Coleoptera: Scarabaeidae), that were feeding on
      the roots of strawberry in Aydin, Turkey. Laboratory studies were conducted to
      (1) observe whether H. larvicolus feeds and completes its life cycle on the
      various stages of S. polyphyllae or other astigmatid mites, such as Acarus siro,
      Carpoglyphus lactis and Tyrophagus putrescentiae (Acaridae), and to determine its
      population growth when feeding on these prey, and (2) to determine development
      periods, longevity and fecundity of H. larvicolus feeding on C. lactis. Hypoaspis
      larvicolus females did not feed on S. polyphyllae, but fed, developed and
      reproduced when A. siro, C. lactis or T. putrescentiae were provided as prey.
      Hypoaspis larvicolus is larviparous as well as oviparous. The female lays eggs or
      gives birth to larvae. If a female gives birth to a larva, it is attached under
      the female's venter for 1-2 days, a phenomenon recorded for the first time in
      Hypoaspis; in fact, for the first time in mites. The results of the population
      growth experiments revealed that H. larvicolus feeding on C. lactis produced the
      highest number of eggs, juveniles and adults. The developmental periods of H.
      larvicolus feeding on C. lactis at life-cycle path I (larva to adult) and II (egg
      to adult) were 12.2 +/- 0.3 and 15.6 +/- 0.6 days (females) and 19.5 +/- 0.2 and
      20.9 +/- 0.4 days (males), respectively. Longevity of females versus males of H.
      larvicolus was 120.6 +/- 7.2 versus 91.6 +/- 13.1 days (life cycle I) and 110.0
      +/- 27.7 versus 118.3 +/- 10.9 days (life cycle II), respectively.

PMID- 30109450
TI  - Assessing Shared Decision-Making Clinical Behaviors Among Genetic Counsellors.
AB  - Shared decision-making (SDM) is a collaborative approach in which clinicians
      educate, support, and guide patients as they make informed, value-congruent
      decisions. SDM improves patients' health-related outcomes through increasing
      knowledge, reducing decisional conflict, and enhancing experience of care. We
      measured SDM in genetic counselling appointments with 27 pregnant women who were
      at increased risk to have a baby with a genetic abnormality. The eight
      experienced genetic counsellors who participated had no specific SDM training and
      were unaware that SDM was being assessed. Audio transcripts of appointments were
      scored using 'Observing Patient Involvement in Decision Making' (OPTION12).
      Patients' anxiety and decisional conflict were also assessed. The genetic
      counsellors' mean OPTION12 score was 42.4% (SD 9.0%; possible range 0-100%).
      Specific SDM behaviours that scored highest included introducing the concept of
      equipoise and listing all options with their pros and cons. Behaviours that
      scored lowest included eliciting patients' preferred approach to receiving
      information and desired degree of involvement in decision-making. Patients'
      levels of anxiety and decisional conflict were unassociated with genetic
      counsellors' OPTION12 scores. Some SDM behaviours were better demonstrated in
      this prenatal genetic counselling study than others. Formal training of genetic
      counsellors in SDM may enhance use of this approach in their professional
      practice.

PMID- 30109451
TI  - Risk Communication in Families of Children with Familial Hypercholesterolemia:
      Identifying Motivators and Barriers to Cascade Screening to Improve Diagnosis at
      a Single Medical Center.
AB  - Familial hypercholesterolemia (FH) is severely underdiagnosed in the USA; yet,
      factors influencing family notification about risk for FH in the US pediatric
      setting have not been well elucidated. Most previous research on these factors
      has occurred in adult patient populations in European countries with organized
      cascade screening programs; therefore, we sought to characterize parent
      experiences with cascade screening in the US pediatric setting. A quantitative
      survey measuring family notification of FH risk information was administered to
      38 parents of children with FH identified within a pediatric cardiology clinic.
      Participants were also asked if family notification was impacted by
      intrapersonal, interpersonal, institutional, community, and public policy factors
      identified previously in other populations. Notification of at least one of the
      proband's living grandparents or aunts/uncles was reported by 76% (n = 25/33) and
      71% (n = 24/34) of participants, respectively. The most common reason for
      notification was to protect relatives from heart disease. Two of the most common
      reasons participants did not notify relatives were a lack of information about FH
      and concern that the relative would have difficulty understanding the
      information. Yet, only a minority of participants (39%) accessed institutional
      resources such as educational materials to share with relatives or assistance
      drafting a family letter that could address these barriers. Based on the
      identified barriers and motivators for family communication, we suggest
      facilitators to improve implementation of cascade screening.

PMID- 30109453
TI  - Basal leaflet thickening and color paucity in the echocardiographic evaluation of
      subclinical leaflet thrombosis after transcatheter aortic valve replacement.

PMID- 30109454
TI  - The association of right ventricular dysfunction with in-hospital and 1-year
      outcomes in anterior myocardial infarction.
AB  - In anterior ST-segment elevation myocardial infarction (STEMI), attention paid
      mainly to the left ventricle. The predictive significance of right ventricular
      (RV) dysfunction in patients with anterior STEMI has been frequently neglected.
      In this study, we evaluated the prognostic effect of RV dysfunction on in
      hospital and long-term outcomes in patients with first anterior STEMI. A total of
      350 patients without known coronary artery disease with first anterior STEMI and
      treated with primary percutaneous coronary intervention were prospectively
      enrolled in this study. In-hospital and long-term outcomes were compared between
      two groups of with or without RV dysfunction. In-hospital mortality was
      significantly higher in the RV dysfunction group (26.7% vs. 1.6%, P < 0.001). The
      RV dysfunction group also had a higher incidence of cardiogenic shock, recurrent
      myocardial infarction, target lesion revascularization and stent thrombosis. The
      1-year overall survival in patients with and without RV dysfunction was 62.2% and
      95.0% respectively. After multivariable analysis, RV dysfunction remained as an
      independent predictor for in-hospital and long-term mortality. RV dysfunction is
      an independent predictor of cardiogenic shock, recurrent myocardial infarction,
      and, in-hospital and long-term mortality in anterior STEMI. Therefore, attention
      should be paid to the function of right ventricle as in the left ventricle after
      anterior STEMI.

PMID- 30109455
TI  - The implementation of a longitudinal POCUS curriculum for physicians working at
      rural outpatient clinics in Chiapas, Mexico.
AB  - BACKGROUND: Medical care in resource limited settings is challenging,
      particularly with limited access to diagnostic and imaging studies. The most
      portable and cost effective diagnostic imaging in these areas is ultrasound.
      Ultrasound is a very teachable skill with a short, single intensive training
      course and hands-on teaching; however, there are limited data on a longitudinal
      point-of-care ultrasound (POCUS) curriculum in resource limited settings. The
      goal of this intervention is to develop an effective longitudinal POCUS
      curriculum for local physicians working in rural clinics in the state of Chiapas,
      Mexico, and evaluate its effectiveness on patient care. METHODS: This is a 12
      month longitudinal ultrasound educational curriculum for local supervising
      physicians working in rural clinics in Chiapas, Mexico. The 10 clinics are a
      collaboration of the Mexican government and Companeros En Salud with limited
      access to any diagnostic imaging or laboratory studies. The investigators
      assisted in obtaining four portable ultrasound machines for use in the clinics.
      Next, they organized four point-of-care ultrasound (POCUS) teaching sessions over
      a year, each session focusing on several distinct concepts. The sessions included
      lectures and hands-on teaching with both healthy volunteers and with patients in
      the various communities. Over the 12 months, the POCUS were logged and the
      majority of images saved. The logs were analyzed to determine if POCUS affected
      the medical management of the patients. The primary investigator reviewed 35.2%
      of the total ultrasounds completed, which was 52.2% of the save images, for
      quality assurance and feedback. RESULTS: Over the 12 months, there were 584
      ultrasound studies documented. The most common study was a transabdominal
      obstetric examination (45.5%) followed by abdomen/pelvis (26.6%) and
      musculoskeletal (5.7%) and skin and soft tissue (5.7%). The use of POCUS changed
      the patient diagnosis after 194 scans (34%) and changed the clinical management
      for the patient encounter in 171 (30%) scans. In the 194 scans in which POCUS
      changed the diagnosis, the clinical management was changed, as a direct result of
      the scan results, in 152 (78.4%) of those patient encounters. CONCLUSION: A
      longitudinal POCUS educational curriculum is an effective way to equip local
      physicians in resource limited countries with a tool to improve their clinical
      management of patients.

PMID- 30109456
TI  - A Randomized Controlled Trial to Increase HIV Testing Demand Among Female Sex
      Workers in Kenya Through Announcing the Availability of HIV Self-testing Via Text
      Message.
AB  - We assessed whether informing female sex workers about the availability of HIV
      self-testing at clinics in Kenya using text messages would increase HIV testing
      rates. We selected a sample of 2196 female sex workers registered in an
      electronic health record system who were irregular HIV testers and randomized
      them to be sent a text message announcing the availability of (1) HIV self-test
      kits sent three times (intervention), (2) general HIV testing sent three times
      (enhanced standard of care [SOC]), or (3) general HIV testing sent one time
      (traditional SOC). Participants in the intervention arm were significantly more
      likely to test for HIV during 2-month follow-up compared to those in the enhanced
      SOC (OR 1.9, p = 0.001). There was no difference in HIV testing between those in
      the enhanced SOC and the traditional SOC arms. Announcing the availability of HIV
      self-testing via text message increased HIV testing among this high-risk group.

PMID- 30109457
TI  - HIV Testing, Risk Behaviors, and Fear: A Comparison of Documented and
      Undocumented Latino Immigrants.
AB  - Latino immigrants in the United States are at elevated risk for HIV infection and
      delayed HIV diagnosis. Immigration documentation status and its contribution to
      fears are important barriers to accessing health services including HIV testing.
      A currently changing political climate within the United States may have
      increased the complexity of the intersection of documentation status and health
      care access. This study used an anonymous survey conducted in March and April
      2017 in New York City to compare: sociodemographic characteristics, HIV testing
      behaviors, HIV risk behaviors, and perceptions of fear around HIV testing among
      documented and undocumented Latino immigrants (N = 301). We found that
      undocumented immigrants reported lower levels of education, income, and health
      insurance than did documented immigrants. However, groups did not differ in
      having tested for HIV in the last 12 months, in future intentions to test for
      HIV, or in emotional/cognitive perceptions of fear around HIV testing.
      Undocumented immigrants reported lower rates of having ever tested for HIV in
      their lifetime (68.6%) than documented immigrants (80.5%) (p = 0.027). In
      conclusion, we found that despite sociodemographic challenges, undocumented
      immigrants had similar HIV testing behaviors as their documented counterparts in
      our study community. Further understanding of the mitigating factors that
      resulted in seemingly equal access to HIV testing in this community for
      undocumented immigrants is warranted.

PMID- 30109452
TI  - Tetracycline repurposing in neurodegeneration: focus on Parkinson's disease.
AB  - The prevalence of Parkinson's disease, which affects millions of people
      worldwide, is increasing due to the aging population. In addition to the classic
      motor symptoms caused by the death of dopaminergic neurons, Parkinson's disease
      encompasses a wide range of nonmotor symptoms. Although novel disease-modifying
      medications that slow or stop Parkinson's disease progression are being
      developed, drug repurposing, which is the use of existing drugs that have passed
      numerous toxicity and clinical safety tests for new indications, can be used to
      identify treatment compounds. This strategy has revealed that tetracyclines are
      promising candidates for the treatment of Parkinson's disease. Tetracyclines,
      which are neuroprotective, inhibit proinflammatory molecule production, matrix
      metalloproteinase activity, mitochondrial dysfunction, protein
      misfolding/aggregation, and microglial activation. Two commonly used
      semisynthetic second-generation tetracycline derivatives, minocycline and
      doxycycline, exhibit effective neuroprotective activity in experimental models of
      neurodegenerative/ neuropsychiatric diseases and no substantial toxicity.
      Moreover, novel synthetic tetracyclines with different biological properties due
      to chemical tuning are now available. In this review, we discuss the multiple
      effects and clinical properties of tetracyclines and their potential use in
      Parkinson's disease treatment. In addition, we examine the hypothesis that the
      anti-inflammatory activities of tetracyclines regulate inflammasome signaling.
      Based on their excellent safety profiles in humans from their use for over 50
      years as antibiotics, we propose the repurposing of tetracyclines, a multitarget
      antibiotic, to treat Parkinson's disease.

PMID- 30109458
TI  - Clonal Saplings of Trembling Aspen Do Not Coordinate Defense Induction.
AB  - Induction of plant chemical defenses in response to insect feeding may be
      localized to the site of damage or expressed systemically, mediated by signal
      transduction throughout the plant. Such systemic induction processes have been
      widely investigated in plants with single stems, but rarely in clonal plants
      comprised of multiple ramets with vascular connections. For a clonal tree species
      such as trembling aspen (Populus tremuloides Michx), integration of induced
      defense within clones could be adaptive, as clones are spatially extensive and
      susceptible to outbreak herbivores. We used pairs of aspen saplings with shared
      roots, replicated from three genotypes, to determine whether defense-induction
      signals are communicated within clones. One ramet in each pair was subjected to a
      damage treatment (feeding by Lymantria dispar, followed by mechanical damage),
      and subsequent changes in leaf defensive chemistry were measured in both ramets.
      Responses to damage varied by defense type: condensed tannins (CTs) increased in
      damaged ramets but not in connected undamaged ramets, whereas salicinoid phenolic
      glycosides (SPGs) were not induced in any ramets. Genotypes varied in their
      levels of CTs, but not in their levels of SPGs, and responded similarly to damage
      treatment. These results suggest that, even with both vascular and volatile
      information available, young aspen ramets do not induce defenses based on signals
      or metabolites from other ramets. Thus, unlike other clonal plant species, aspen
      do not appear to coordinate defense induction within clones. Lack of coordinated
      early induction in aspen may be related to the function of CTs in tolerance,
      rather than resistance.

PMID- 30109459
TI  - Liquified Petroleum Gas (LPG) Supply and Demand for Cooking in Northern Ghana.
AB  - Like many other countries, Ghana relies on biomass (mainly wood and charcoal) for
      most of its cooking needs. A national action plan aims to expand liquefied
      petroleum gas (LPG) access to 50% of the country's population by 2020. While the
      country's southern urban areas have made progress toward this goal, LPG use for
      cooking remains low in the north. The aim of this cross-sectional study was to
      characterize the current state of the LPG market in this area and examine
      opportunities and barriers to scale up LPG adoption. We interviewed 16 LPG
      suppliers (stove, cylinder, and fuel vendors) as well as 592 households in the
      Kassena-Nankana Districts (KND) of Ghana. We find large rural-urban differences
      in LPG uptake: less than 10% of rural households own LPG stoves compared with
      over half of urban households. Awareness of LPG is high across the region, but
      accessibility of fuel supply is highly limited, with just one refilling station
      located in the KND. Affordability is perceived as the main barrier to LPG
      adoption, and acceptability is also limited by widespread concerns about the
      safety of cooking with LPG. Transitioning to a cylinder recirculation model, and
      providing more targeted subsidies and credit options, should be explored to
      expand access to cleaner cooking in this region.

PMID- 30109460
TI  - Today's advanced is tomorrow's basic.

PMID- 30109461
TI  - Persistence in Stochastic Lotka-Volterra Food Chains with Intraspecific
      Competition.
AB  - This paper is devoted to the analysis of a simple Lotka-Volterra food chain
      evolving in a stochastic environment. It can be seen as the companion paper of
      Hening and Nguyen (J Math Biol 76:697-754, 2018b) where we have characterized the
      persistence and extinction of such a food chain under the assumption that there
      is no intraspecific competition among predators. In the current paper, we focus
      on the case when all the species experience intracompetition. The food chain we
      analyze consists of one prey and [Formula: see text] predators. The jth predator
      eats the [Formula: see text]st species and is eaten by the [Formula: see text]st
      predator; this way each species only interacts with at most two other species-the
      ones that are immediately above or below it in the trophic chain. We show that
      one can classify, based on the invasion rates of the predators (which we can
      determine from the interaction coefficients of the system via an algorithm),
      which species go extinct and which converge to their unique invariant probability
      measure. We obtain stronger results than in the case with no intraspecific
      competition because in this setting we can make use of the general results of
      Hening and Nguyen (Ann Appl Probab 28:1893-1942, 2018a). Unlike most of the
      results available in the literature, we provide an in-depth analysis for both non
      degenerate and degenerate noise. We exhibit our general results by analyzing
      trophic cascades in a plant-herbivore-predator system and providing
      persistence/extinction criteria for food chains of length [Formula: see text].

PMID- 30109462
TI  - NMR assignments for monomeric phage L decoration protein.
AB  - Phage L encodes a trimeric 43 kDa decoration protein (Dec) that noncovalently
      binds and stabilizes the capsids of the homologous phages L and P22 in vitro. At
      physiological pH Dec was unsuitable for NMR. We were able to obtain samples
      amenable for NMR spectroscopy by unfolding Dec to pH 2 and refolding it to pH 4.
      Our unfolding/refolding protocol converted trimeric Dec to a folded 14.4 kDa
      monomer. We verified that the acid-unfolding protocol did not perturb the
      secondary structure, or the capsid-binding function of refolded Dec. We were able
      to obtain complete 1H, 15N, and 13C assignments for the Dec monomer, as well as
      information on its secondary structure and dynamics based on chemical shift
      assignments. The assigned NMR spectrum is being used to determine the three
      dimensional structure of Dec, which is important for understanding how the trimer
      binds phage capsids and for the use of the protein as a platform for phage
      display nanotechnology.

PMID- 30109464
TI  - Interview with Prof. Marion Smits, President of the 41st Annual Meeting of the
      ESNR : The 41st ESNR Annual Meeting will take place in Rotterdam, the
      Netherlands, from 19 to 23 September 2018.

PMID- 30109463
TI  - End of Life Care for Older Russian Immigrants - Perspectives of Russian
      Immigrants and Hospice Staff.
AB  - This pilot study examined immigrant Russian seniors and adult children's views on
      end-of-life care, and hospice staff members' experiences providing care to
      diverse immigrant clients, in areas of North Carolina with a high proportion of
      immigrants. Data were collected through individual in-depth interviews with
      informants, including Russian immigrant seniors, Russian adult children, and
      hospice staff, and analyzed by qualitative techniques. Findings indicate that
      there is little awareness of end-of-life care options among the Russian immigrant
      community in North Carolina. End-of-life care is rarely discussed within the
      family of first generation Russian immigrants but second-generation families are
      more open to doing so. First generation immigrant Russian seniors in our study do
      not seem to want any specialized end-of-life care often due to lack of awareness,
      and prefer family care. Second generation seniors' attitudes are more accepting
      of this type of care. Hospice staff serve all those who seek care, receive
      training to serve diverse clients, and prioritize professional policies. There is
      sometimes potential for a gap between hospice policies regarding care and
      immigrant families' expectations for care. Results suggest a great need for
      community outreach to immigrant groups to raise awareness of end-of-life care,
      including advance directives and hospice care and the role of interpreters in
      health care settings.

PMID- 30109465
TI  - Anti-GABAB receptor encephalitis in a patient with gastric adenocarcinoma.
AB  - Anti-gamma-aminobutyric acid-B (GABAB) receptor encephalitis is an autoimmune
      encephalitis associated with antibodies against neuronal cell surface antigens,
      which are primarily observed with small-cell lung cancer, melanoma, and thymoma.
      Here, we first report a case on the association between a relatively frequent
      cancer, gastric adenocarcinoma (GAC), and a rare GABAB receptor antibody limbic
      encephalitis. The patient was treated with immunotherapy and combined-drug
      chemotherapy, which were partially effective in terms of stabilizing the tumor
      and relieving neurological symptoms. This report indicates that, when patients
      present with GABAB receptor antibody limbic encephalitis, regular and broad
      screening for tumors including gastric adenocarcinoma should also be considered.

PMID- 30109467
TI  - Restoration of fertility in a young patient with spinal cord injury: is there a
      place for noninvasive neurostimulation?

PMID- 30109466
TI  - Disease progression in Parkinson subtypes: the PPMI dataset.
AB  - INTRODUCTION: Discrete patterns of progression have been suggested for patients
      with Parkinson disease and presenting tremor dominant (TD) or postural
      instability gait disorders (PIGD). However, longitudinal prospective assessments
      need to take into consideration the variability in clinical manifestations and
      the evidence that only 40% of initially classified PIGD remain in this subtype at
      subsequent visits. METHODS: We analyzed clinical progression of PIGD compared to
      TD using longitudinal clinical data from the PPMI. Given the reported instability
      of such clinical classification, we only included patients who were reported as
      PIGD/TD at each visit during the 4-year observation. We used linear mixed-effects
      models to test differences in progression in these subgroups in 51 dependent
      variables. RESULTS: There were 254 patients with yearly assessment. The number of
      PIGD was 36/254 vs 144/254 TD. PIGD had more severe motor disease at baseline but
      progressed faster than TD only in three non-motor items of the MDS-UPDRS:
      cognitive impairment, hallucinations, and psychosis plus features of DDS. Our
      analysis also showed in PIGD faster increase in the average time with dyskinesia.
      CONCLUSIONS: PIGD are characterized by more severe disease manifestations at
      diagnosis and greater cognitive progression, more frequent hallucinations,
      psychosis as well as features of DDS than TD patients. We interpret these
      findings as expression of greater cortical and subcortical involvement in PIGD
      already at onset. Since PIGD/TD classification is very unstable at onset, our
      analysis based on stricter definition criteria provides important insight for
      clinical trial stratification and definition of related outcome measures.

PMID- 30109469
TI  - Current Approaches in the Management of Hepatic Adenomas.
AB  - INTRODUCTION: Hepatic adenomas (HAs) are a benign and relatively rare type of
      liver neoplasms. We review the diagnosis, evaluation, and potential therapeutic
      management options for patients with HA. METHODS: A comprehensive review of the
      English literature was performed utilizing MEDLINE/PubMed and Web of Science
      databases with end of search date the 30th April of 2018. In PubMed, the terms
      "hepatocellular," "hepatic," "liver," and "adenoma," "adenomatosis" were searched
      in the title and/or abstract. RESULTS: Recent advances in molecular
      classification of HA have determined distinct subtypes with specific clinical,
      pathological, and imaging characteristics. In general, cessation of exogenous
      hormonal administration or weight loss may lead to HA regression. Surgical
      resection, either open or laparoscopic, should be considered in patients with
      symptoms and risk factors for hemorrhage or malignant transformation. These risk
      factors include tumor diameter greater than 5 cm, beta-catenin activated subtype,
      and/or male gender. The management of acute hemorrhage should primarily aim at
      achieving hemodynamic stability via angioembolization followed by elective
      resection, whereas malignant transformation is treated according to oncologic
      resection principles. Although pregnancy is one of the known risk factors for
      tumor growth and associated complications, the presence of an HA per se should
      not be considered a contradiction to pregnancy. CONCLUSION: Future genomic-based
      multicenter studies are required to provide a strong basis for formulating an
      evidence-based risk-adapted model that guides individualized management
      strategies for patients with HA.

PMID- 30109470
TI  - The 5-HT4 Receptor Agonist Prucalopride Stimulates Mucosal Growth and Enhances
      Carbohydrate Absorption in the Ileum of the Mouse.
AB  - BACKGROUND: Enteric serotonin may function as a mucosal growth factor. Previous
      work demonstrated increased crypt cell proliferation and intestinal mucosal
      surface area with potentiation of serotonin. While an indirect mechanism was
      postulated to explain these effects, the presence of 5-HT4 receptors on
      enterocytes raises the possibility of a direct action of serotonin. We
      hypothesized that a 5-HT4 specific agonist, prucalopride, would stimulate
      intestinal mucosal growth and enhance absorptive function in the murine small
      intestine. METHODS: Adult wild-type mice were treated parenterally with
      prucalopride for 14 days via surgically implanted osmotic pumps. In vivo D-xylose
      absorption was assessed by oral gavage and serum D-xylose measurements. On day
      14, glucose absorption was assessed by instilling a glucose solution into
      isolated segments of small intestine. The bowel was harvested and examined for
      morphologic parameters and crypt cell proliferation. RESULTS: Villus height,
      crypt depth, and crypt proliferation were significantly increased in the distal
      small bowel of prucalopride-treated mice compared with control animals. Crypt
      depth was also increased in the proximal and middle small intestine in treated
      mice. There was no difference in D-xylose absorption throughout the study period;
      however, glucose absorption was significantly increased in the distal small
      intestine of prucalopride-treated mice. CONCLUSION: Parenteral administration of
      the 5-HT4 receptor specific agonist, prucalopride, results in morphologic and
      functional changes in the murine small intestine that are most prominent in the
      distal small bowel. While further studies are necessary to delineate the
      mechanism, it is plausible that the effects are mediated by 5-HT4 receptors on
      enterocytes.

PMID- 30109468
TI  - Pharmacological Comparisons Between Cannabidiol and KLS-13019.
AB  - Cannabidiol (CBD) exhibits neuroprotective properties in many experimental
      systems. However, development of CBD as a drug has been confounded by the
      following: (1) low potency; (2) a large number of molecular targets; (3) marginal
      pharmacokinetic properties; and (4) designation as a schedule 1 controlled
      substance. The present work compared the properties of CBD with a novel molecule
      (KLS-13019) that has structural similarities to CBD. The design strategy for KLS
      13019 was to increase hydrophilicity while optimizing neuroprotective potency
      against oxidative stress toxicity relevant to hepatic encephalopathy. The
      protective responses of CBD and KLS-13019 were compared in dissociated rat
      hippocampal cultures co-treated with toxic levels of ethanol and ammonium
      acetate. This comparison revealed that KLS-13019 was 31-fold more potent than CBD
      in preventing neuronal toxicity from the combined toxin treatment, while both
      compounds exhibited complete protective efficacy back to control values. In
      addition, treatment with KLS-13019 alone was 5-fold less toxic (TC50) than CBD.
      Previous studies suggested that CBD targeted the Na+-Ca2+ exchanger in
      mitochondria (mNCX) to regulate intracellular calcium levels, an important
      determinant of neuronal survival. After treatment with an inhibitor of mNCX (CGP
      37157), no detectable neuroprotection from ethanol toxicity was observed for
      either CBD or KLS-13019. Furthermore, AM630 (CB2 antagonist) significantly
      attenuated CBD-mediated neuroprotection, while having no detectable effect on
      neuroprotection from KLS-13019. Our studies indicated KLS-13019 was more potent
      and less toxic than CBD. Both compounds can act through mNCX. KLS-13019 may
      provide an alternative to CBD as a therapeutic candidate to treat diseases
      associated with oxidative stress.

PMID- 30109471
TI  - A qualitative study of patients' perceptions of the utility of patient-reported
      outcome measures of symptoms in primary care clinics.
AB  - PURPOSE: Sleep, pain, anxiety, depression, and low energy/fatigue (SPADE pentad)
      symptoms are common, but often unrecognized and undertreated in primary care. In
      an effort to improve symptom outcomes, primary care clinics are integrating
      patient-reported outcome measures (PROs), such as the Patient-Reported Outcome
      Measurement Information System (PROMIS), into practice. Whether patients with
      SPADE symptoms perceive these measures as useful is unknown. The purpose of this
      qualitative study was to explore patients' perceptions of the utility of symptom
      based PROs in primary care. METHODS: As part of a mixed-methods study, 23
      patients (age 24-77 years) with one or more SPADE symptoms participated in one-on
      one interviews about the use, implementation and visual display of PROMIS. All
      interviews were audio-recorded, transcribed, and analyzed using thematic
      analysis. RESULTS: Five themes emerged: (1) PROs may foster communication about
      symptoms; (2) data from PROs may prompt clinical actions; (3) the visual display
      of symptom scores could be useful for patients and providers, though
      modifications may enhance interpretation; (4) implementation may vary according
      to patients' perception of PRO features (e.g., length); and (5) PROs may be
      useful, but only to the extent that they are valued, prioritized, and used.
      CONCLUSIONS: According to patients, the use of PROs to measure symptoms in
      primary care clinics has the potential to be useful. However, patients are
      reluctant to complete PROs if they perceive that clinicians do not use the
      measures to improve care. Barriers to implementation in primary care (e.g.,
      duration of visit) should be addressed to enhance the utility of PROs. Clinical
      trial registration ClinicalTrials.gov ID: NCT02383862.

PMID- 30109472
TI  - Ectomycorrhizae formed by three Japanese truffle species (Tuber japonicum, T.
      longispinosum, and T. himalayense) on indigenous oak and pine species.
AB  - Modern truffle cultivation systems started in Europe in the early 1970s and are
      now successfully used for several European truffles throughout the world.
      However, systems for indigenous novel truffle species need to be developed in
      several regions, especially where truffle cultivation has not been attempted so
      far, such as in Japan. Recently, two new and one known truffle species that are
      expected to be edible were reported from Japan: Tuber japonicum, T.
      longispinosum, and T. himalayense. Here, we conducted mycorrhization trials
      between these three truffle species and four native tree species in Japan
      (Quercus acutissima, Q. phillyraeoides, Q. serrata, and Pinus densiflora) using
      spore suspension and trap-plant seedling techniques under axenic pot culture
      conditions to understand their potential host ranges and mycorrhizal morphologies
      and to determine whether these inoculation methods are applicable for
      mycorrhization of Japanese truffles with native host plants. Of the 12
      combinations, nine were successful for mycorrhization, including both oak and
      pine trees. The T. japonicum mycorrhiza was characterized by short, needle-shaped
      cystidia without septa, whereas the two black truffles, T. longispinosum and T.
      himalayense, were indistinguishable from each other because they shared the same
      morphological and anatomical characters such as brownish, long cystidia with
      right angle ramification. These features were similar to related black truffle
      species. The results of the present study indicate that the inoculation method
      used for European truffles can also be applied for mycorrhization between
      Japanese truffle species and compatible native pine and/or oak hosts in Japan.

PMID- 30109474
TI  - A Randomized, Placebo-Controlled, Blinded, Crossover, Pilot Study of the Effects
      of Dextromethorphan/Quinidine for the Treatment of Neurobehavioral Symptoms in
      Adults with Autism.
AB  - Prior studies have demonstrated successful irritability treatment using
      dopaminergic antagonists in autistic patients. The purpose of this pilot study
      was to assess the effect of dextromethorphan/quinidine (DM/Q) in autistic adults
      (18-60 years of age). This was a randomized, blinded, crossover, study of 14
      patients randomized to DM/Q or a placebo for 8 weeks, washed out for 4 weeks,
      then crossed over to the opposite treatment. There were no serious adverse
      events. Subjects were significantly lower on the Aberrant Behavioral Checklist
      for Irritability (ABC-IR) (F1,10 = 7.42; p = 0.021). Improvements in aggression
      and Clinical Global Impression were also seen. The findings suggest that DM/Q is
      well-tolerated and associated with improvements in irritability and aggression in
      adults with autism.

PMID- 30109473
TI  - Plant host habitat and root exudates shape fungal diversity.
AB  - The rhizospheric microbiome is clearly affected by plant species and certain of
      their functional traits. These functional traits allow plants to adapt to their
      environmental conditions by acquiring or conserving nutrients, thus defining
      different ecological resource-use plant strategies. In the present study, we
      investigated whether plants with one of the two nutrient-use strategies
      (conservative versus exploitative) could influence fungal communities involved in
      soil organic matter degradation and root exudate assimilation, as well as those
      colonizing root tissues. We applied a DNA-based, stable-isotope probing (DNA-SIP)
      approach to four grass species distributed along a gradient of plant nutrient
      resource strategies, ranging from conservative to exploitative species, and
      analyzed their associated mycobiota composition using a fungal internal
      transcribed spacer (ITS) and Glomeromycotina 18S rRNA gene metabarcoding
      approach. Our results demonstrated that fungal taxa associated with exploitative
      and conservative plants could be separated into two general categories according
      to their location: generalists, which are broadly distributed among plants from
      each strategy and represent the core mycobiota of soil organic matter degraders,
      root exudate consumers in the root-adhering soil, and root colonizers; and
      specialists, which are locally abundant in one species and more specifically
      involved in soil organic matter degradation or root exudate assimilation on the
      root-adhering soil and the root tissues. Interestingly, for arbuscular
      mycorrhizal fungi analysis, all plant roots were mainly colonized by Glomus
      species, whereas an increased diversity of Glomeromycotina genera was observed
      for the exploitative plant species Dactylis glomerata.

PMID- 30109476
TI  - Abstract 2018.

PMID- 30109477
TI  - Context Matters: Examining Perceived Health and Fitness Outcomes of Physical
      Activity Participation Among South Korean Adults and Youth.
AB  - PURPOSE: To examine associations between physical activity contexts and health
      and fitness perceptions among Korean adults and youth. METHOD: Data were from the
      Korean Survey on Citizens' Sports Participation in 2015. Korean youth (N = 832;
      Mage = 14.7) and adults (N = 6719; Mage = 41.3) were included in the hierarchical
      logistic and linear regressions. Youth physical activity was examined in school
      based (i.e., school-based and after-school/Saturday school sports) and out of
      school (i.e., organized sports) settings. Adults who met the World Health
      Organization (WHO) physical activity guidelines or not, and participated in
      structured (e.g., sport) and unstructured (e.g., walking) physical activity were
      compared. The outcome variables were self-reported health and fitness. Gender
      interactions between physical activity and all outcomes were examined for the
      adult sample only. RESULTS: No associations existed between physical activity and
      perceived health or fitness among youth. Adults who met the WHO guidelines, or
      participated in structured physical activity showed higher odds of reporting good
      health. Unstructured physical activity was associated with lower odds of
      reporting good health. Positive perceptions of fitness were more likely to be
      reported by males who met physical activity guidelines compared to females.
      CONCLUSIONS: For youth, the potential benefit of physical activity, regardless of
      contexts, may be more apparent for psychological health than perceived physical
      health, and school should be used as a venue to promote physical activity. For
      adults, structured physical activity and achieving the WHO physical activity
      guidelines may be suggested for perceptions of overall health.

PMID- 30109475
TI  - Biphenotypic sinonasal sarcoma: demographics, clinicopathological
      characteristics, molecular features, and prognosis of a recently described
      entity.
AB  - Biphenotypic sinonasal sarcoma (BSNS) is a recently recognized type of sarcoma
      arising exclusively in the sinonasal tract displaying unique clinical course,
      histopathology, and genetics. Due to its rarity, only case series and case
      reports are available. In order to provide an overview of the current
      understanding of this disease, we present a comprehensive review of the
      literature and present three previously unreported cases of BSNS. A total of 55
      genetically characterized and 41 cases without molecular data were identified in
      the literature. Two-thirds of patients were female and the peak incidence was in
      the fifth decade. Fatal outcome was rare (two cases with intracranial extension)
      and local recurrence occurred in 31.6%, all occurring within 5 years after
      initial treatment. Histologically, BSNS is highly cellular in the majority of
      cases and composed of fascicles of spindle cells, with entrapped hyperplastic
      surface epithelium being a frequent finding. The immunohistochemical profile is
      characteristic due to the biphasic nature of this lesion, with shared features of
      both myogenic and neural origin. Rhabdomyoblastic differentiation is apparent in
      a subset of cases. The most common genetic event is the PAX3-MAML3 fusion (58.6%)
      but isolated PAX3 rearrangement (19.2%), absence of rearrangements (9.1%), PAX3
      FOXO1 (8.1%), PAX3-NCOA1 (4%), and isolated MAML3 rearrangement (2%) have also
      been reported. In conclusion, the recognition of BSNS is crucial due to its
      relatively indolent clinical course. A selected immunohistochemical panel and/or
      molecular confirmation can be used to aid in appropriate diagnosis and
      consequently in prognostication and to avoid overtreatment with chemotherapy
      regimens used in its mimics.

PMID- 30109479
TI  - Clinical, imaging, and histological presentations and outcomes of stroke related
      to sarcoidosis.
AB  - OBJECTIVES: Clinical involvement of the nervous system is uncommon during
      sarcoidosis. Cerebrovascular events are rarely reported during sarcoidosis and
      may be confused with primary angiitis of the central nervous system. The
      characteristics and outcomes of cerebrovascular events during sarcoidosis have
      not been well-evaluated. PATIENTS AND METHODS: We conducted a retrospective case
      series in our institution with an updated review of the literature from 1962 to
      2017 to characterize the clinical presentation, imaging, histology and outcomes
      of stroke that were thought to be causally related to sarcoidosis. RESULTS: Fifty
      one patients (31 men, median age at stroke diagnosis of 41 years) receiving a
      diagnosis of stroke and sarcoidosis, including 8 new cases from our institution
      and 43 from the literature review, were included. Stroke was the first
      manifestation of sarcoidosis in 64%. The stroke was ischemic in 69% and
      hemorrhagic in 31%. A total of 31% experienced a transient ischemic attack before
      ischemic stroke. A total of 36% of patients had multiple infarcts or hemorrhages.
      The median number of cardiovascular risk factors was 0. Concerning histological
      presentation, vascular or perivascular involvement was present in all cases.
      After a median follow-up of 12 months (after stroke), up to 50% of patients had
      developed a permanent neurological impairment, 16% had a recurrence of stroke,
      and 23% died. CONCLUSIONS: Cerebrovascular events may be the first manifestation
      of neurosarcoidosis, and have a prognosis impact in such patients, leading to
      death and permanent neurological impairment.

PMID- 30109478
TI  - Impaired brain response to odors in patients with varied severity of olfactory
      loss after traumatic brain injury.
AB  - Traumatic brain injury (TBI) as a major public health problem may lead to
      olfactory dysfunction. However, little is known about brain responses to odors in
      TBI olfactory loss patients. Nineteen healthy controls and forty TBI olfactory
      dysfunctional patients (19 with hyposmia and 21 with anosmia) underwent a
      functional magnetic resonance imaging scan when two odors (peach and coffee) were
      presented intranasally using a computerized olfactometer. Olfactory performance
      was measured using the "Sniffin' Sticks" test. TBI patients with hyposmia or
      anosmia showed decreased odor-induced brain activations in the primary olfactory
      area and insular cortex as compared to healthy controls (FWE-corrected peak p <
      0.05). In addition, negative correlations were found between the time since
      injury (in month) and odor-induced brain responses in the right primary olfactory
      area for patients with hyposmia. Similar correlations were seen in the insula and
      orbitofrontal cortex for patients with anosmia. In conclusion, results from the
      current study are evidences for the impairment of central nervous processing of
      odor perception at all levels of the olfactory system among TBI patients with
      olfactory loss. In addition, the duration after the initial injury may have an
      impact on the severity of olfactory dysfunction.

PMID- 30109480
TI  - Anti-JC virus antibody index changes in rituximab-treated multiple sclerosis
      patients.
AB  - Rituximab, a monoclonal antibody to CD20, is an effective treatment for relapsing
      remitting multiple sclerosis (MS) reducing relapse rate by at least 50% over
      time. Although the mechanism for this clinical benefit is unclear, rituximab
      depletes circulating B cells, which can perform antigen presentation and
      stimulation of T cells. Another anti-CD20 drug, ocrelizumab, has recently been
      FDA approved to treat both relapsing remitting and progressive forms of MS. While
      long-term effects of ocrelizumab use are essentially unknown, long-term use of
      rituximab has been associated with the development of progressive multifocal
      leukoencephalopathy (PML) at an incidence of approximately 1/25,000 in non-MS
      conditions. Serostatus for JC virus (JCV), the causative agent for PML, is an
      important risk stratification tool for natalizumab, but its utility in other MS
      treatments is uncertain. We found that rituximab use was associated with a
      reduction in JCV antibody index values in MS patients. Reductions in
      immunoglobulins, IgM in particular, are seen in concert with JCV antibody
      reductions. Physicians should exercise caution when using JCV antibody indices to
      assess any risk of PML for patients on rituximab.

PMID- 30109482
TI  - Fecal diverting device for the substitution of defunctioning stoma: preliminary
      clinical study.
AB  - BACKGROUND: A novel fecal diverting device (FDD) made for the prevention of
      sepsis resulting from anastomotic leakage (AL) was tested successfully in an
      animal study. This study was undertaken to evaluate the clinical safety and
      effectiveness of the FDD. METHODS: A prospective observation trial was
      implemented in a tertiary referral university hospital. The study enrolled
      patients who needed a defunctioning stoma to preserve low-lying rectal
      anastomosis. The FDD was fixed to the proximal colon 15 cm from the anastomosis
      and scheduled to divert feces for 3 weeks. The duration could be extended for
      more than 3 weeks if AL was noted. Postoperative evaluations of AL were performed
      by obtaining a computed tomography (CT) scan after 1 week and a contrast study
      after 3 weeks. The outcomes were FDD-related complications, and the capacity of
      the FDD to preserve the anastomosis. The median follow-up period was 10 (range 5
      40) months. RESULTS: Thirty-one patients, including 5 benign cases, were
      evaluated. There was no case of stoma conversion or surgical re-intervention.
      Evidence of AL was identified in 10 (32%) patients using the CT scan at 1 week
      after surgery. However, in the contrast study at 3 weeks after surgery, only 5
      cases of AL sinus were noted. Conservative treatments including 1-3 weeks
      prolongation of FDD maintenance were enough to preserve the anastomosis. There
      were 3 cases of partial colonic wall erosions at the FDD attachment area. All of
      these patients showed improvement with conservative treatment. The limitations
      were that the study was performed in a single institute and without a control
      group. CONCLUSIONS: The FDD showed a sufficient capacity of fecal diversion and
      maintenance duration that prevented aggravation of sepsis in the case of AL
      without significant complications.

PMID- 30109484
TI  - Perioperative antibiotic prophylaxis in renal transplantation: a single-center
      comparison between two regimens and a brief survey among the Eurotransplant renal
      transplantation centers.
AB  - BACKGROUND: Perioperative antibiotic prophylaxis (PAP) is an integral part of
      kidney transplantation to prevent surgical site infections (SSI). In July 2015,
      we changed our standard from a multiple-dose to a single-dose (SD) prophylaxis.
      Here, we report on results with both regimens and a related survey among
      Eurotransplant renal transplantation centers. METHODS: From July 2015, all kidney
      graft recipients of our center were scheduled to receive SD i.v. cefazolin (group
      SD, n = 107). They were compared to patients, transplanted since January 2014,
      receiving our previous standard (i.v. piperacillin/flucloxacillin) until
      postoperative day (POD) 7, plus oral sultamicillin until POD 10 (group MD, n =
      105). The primary endpoint was the number of SSIs during a 3-month observational
      period. RESULTS: The frequency of SSI episodes was generally low (group SD vs.
      MD: 2 vs. 4, p = 0.40). Of note, urinary tract infections occurred in 40 SD vs.
      36 MD patients, respectively (p = 0.60). Urinary tract infections were caused by
      Escherichia coli in 36.8%. Female gender was the only independent risk factor on
      multivariate analysis (p = 0.002). In addition, 12 episodes of urosepsis in both
      groups occurred. All-cause infection with multi-resistant bacteria occurred less
      frequently in SD vs. MD patients (3.7% vs. 8.6%, p = 0.16). A majority of
      Eurotransplant centers used i.v. single-dose cephalosporins (36.9%), although
      substances and duration varied remarkably. CONCLUSION: Single-dose cefazolin was
      equally effective and less expensive compared to our previous MD regimen. Based
      on these findings, we conclude that future prospective studies should be designed
      to confirm the non-inferiority of single-dose antibiotic regimens.

PMID- 30109483
TI  - ICUD-SIU International Consultation on Bladder Cancer 2017: management of non
      muscle invasive bladder cancer.
AB  - PURPOSE: To provide a summary of the Third International Consultation on Bladder
      Cancer recommendations for the management of non-muscle invasive bladder cancer
      (NMIBC). METHODS: A detailed review of the literature was performed focusing on
      original articles for the management of NMIBC. An international committee
      assessed and graded the articles based on the Oxford Centre for Evidence-based
      Medicine system. The entire spectrum of NMIBC was covered such as prognostic
      factors of recurrence and progression, risk stratification, staging, management
      of positive urine cytology with negative white light cystoscopy, indications of
      bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high
      risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG
      strain and host on outcomes, management of complications of intravesical therapy,
      role of alternative therapies, indications for early cystectomy, surveillance
      strategies, and new treatments. The working group provides several
      recommendations on the management of NMIBC. RESULTS: Recommendations were
      summarized with regard to staging; management of primary and recurrent LG Ta and
      high risk disease, positive urine cytology with negative white light cystoscopy
      and prostatic urethral involvement; indications for timely cystectomy; and
      surveillance strategies. CONCLUSION: NMIBC remains a common and challenging
      malignancy to manage. Accurate staging, grading, and risk stratification are
      critical determinants of the management and outcomes of these patients. Current
      tools for risk stratification are limited but informative, and should be used in
      clinical practice when determining diagnosis, surveillance, and treatment of
      NMIBC.

PMID- 30109485
TI  - Limited sensitivity and size over measurements of ultrasound affect medical
      decisions for ureteral stone compared to non-contrasted computed tomography.
AB  - PURPOSE: To evaluate the limited sensitivity and size over measurements of
      ultrasound (US) for ureteral stone, and demonstrate how this influenced medical
      decisions. PATIENTS AND METHODS: Retrospectively, we analyzed the data of
      patients with ureterolithiasis estimated by US and non-contrasted computed
      tomography (NCCT) within 48 h at our institution from January 1st 2014 to June
      1st 2017. Stone size was grouped by the longest axis diameter on NCCT: < 5, 5-10,
      and > 10 mm. Then, US and NCCT results were compared for the sensitivity and
      measurements. RESULTS: A total of 614 cases of ureterolithiasis were visible on
      NCCT. The sensitivity of US for ureterolithiasis < 5, 5-10, and > 10 mm were
      63.49, 79.06, and 84.67%, respectively (P = 0.001). US overestimated the size in
      63.49 and 50.54% of patients with ureterolithiasis < 5 and 5-10 mm compared to
      NCCT, respectively (P < 0.001). Under the assumptions that patients with ureteral
      stone < 5, 5-10, and > 10 mm would be simply observed, received medical expulsive
      therapy (MET), and surgical interventions, 20.94 and 15.33% of patients with
      stone sized 5-10 and > 10 mm might be improperly observed due to negative US
      reports. Besides, 63.49 and 50.54% of cases with stone < 5 and 5-10 mm might
      receive more aggressive interventions ascribed to over measurements of US.
      CONCLUSIONS: Limited sensitivity and size over measurements of US might
      significantly influence medical decisions for ureteral stone. Inaccurate
      evaluation of US should be taken in consideration for appropriate counseling
      options.

PMID- 30109481
TI  - The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis.
AB  - Psoriasis is a chronic, immune-mediated, inflammatory disease that is
      pathogenically driven by proinflammatory cytokines. This article reviews the
      immunologic role of interleukin (IL)-17, the major effector cytokine in the
      pathogenesis of psoriatic disease, along with the rationale for targeting the IL
      17 cytokine family (IL-17A, IL-17F, and IL-17 receptor A) in the treatment of
      psoriasis and psoriatic arthritis. Emerging evidence indicates that major sources
      of IL-17A in patients with psoriatic disease are mast cells, gammadelta T cells,
      alphabeta T cells, and innate lymphoid cells in lesional skin and synovial fluid.
      Within the skin and joints, IL-17A acts on cellular targets, including
      keratinocytes, neutrophils, endothelial cells, fibroblasts, osteoclasts,
      chondrocytes, and osteoblasts, to stimulate production of various antimicrobial
      peptides, chemokines, and proinflammatory and proliferative cytokines, which, in
      turn, promote tissue inflammation and bone remodeling. The critical importance of
      the IL-23/IL-17A axis to the pathogenesis of psoriatic disease has resulted in
      many new biologic treatments targeting these cytokines. These biologics
      dramatically improve skin and joint symptoms in patients with moderate-to-severe
      psoriasis and psoriatic arthritis.

PMID- 30109486
TI  - In their own words: patient navigator roles in culturally sensitive cancer care.
AB  - PURPOSE: Patient navigation has emerged as a promising strategy in reducing
      disparities among diverse cancer patients. However, little is known about
      navigators' own perspectives on their roles in providing culturally competent
      care. The purpose of the present study is to describe these self-identified
      roles. METHODS: Data were collected from an online survey with a convenience
      sample of cancer patient navigators. Using NVivo 10, qualitative content analysis
      was conducted on free text responses to the question: "In your opinion, what is
      the role of a patient navigator or nurse navigator in the provision of culturally
      sensitive care to patients?" Frequencies of each navigator-identified role
      mentioned were tabulated. RESULTS: Of 294 respondents, 50.7% (n = 149) provided a
      response to the question of interest. Respondents described the following 11
      interrelated navigator roles in the provision of culturally competent care: (1)
      assess and understand patient needs, (2) tailor care to patient, (3) build
      rapport/open communication, (4) facilitate communication between patient and
      health care team, (5) educate/provide resources to the patient, (6) advocate, (7)
      self-motivated learning, (8) address barriers to care, (9) involve/meet the needs
      of family or support people, (10) educate/support health care team, and (11)
      support patient empowerment in care. CONCLUSIONS: Patient navigators are uniquely
      well-positioned to improve cultural competence of cancer care given their role as
      liaison to patients and providers. Cancer care settings should use navigators
      with direct knowledge of patient culture whenever possible; however,
      communication and cultural competence training is highly recommended for all
      navigators given the diversity of patient needs.

PMID- 30109487
TI  - Criterion for trismus in head and neck cancer patients: a verification study.
AB  - PURPOSE: Several cut-off points for trismus in head and neck cancer patients have
      been used. A mouth opening of 35 mm or less is most frequently used as cut-off
      point. Due to the variation in cut-off points, prevalence, risk factors and
      treatment outcomes of trismus cannot be studied in a uniform manner. To provide
      uniformity, we aimed to verify the cut-off point of 35 mm or less. Additionally,
      we aimed to determine associated covariates with reported difficulties when
      opening the mouth. METHODS: In a cross-sectional design, we measured the mouth
      opening in 671 head and neck cancer patients at the Department of Oral and
      Maxillofacial Surgery, at the University Medical Center Groningen. The cut-off
      point was determined using the receiver operating characteristic curve and Youden
      index, with reported difficulties when opening the mouth as criterion for
      trismus. Cut-off points for significant covariates were also determined. RESULTS:
      The Youden index was highest at 35 mm, with a sensitivity of 0.71 and a
      specificity of 0.86. Of the covariates analysed, type of treatment modality was
      significantly associated with reported difficulties when opening the mouth. The
      highest Youden index for patients treated with surgery alone was 37 mm and for
      patients treated with radiotherapy alone 33 mm. CONCLUSIONS: The cut-off point of
      35 mm or less for trismus was confirmed in a head and neck cancer population and
      is recommended to be used in future studies. Patients receiving different
      treatment modalities experience difficulty when opening the mouth differently.

PMID- 30109488
TI  - Retrospective study of the digestive tract mucositis derived from myeloablative
      and non-myeloablative/reduced-intensity conditionings with busulfan in
      hematopoietic cell transplantation patient.
AB  - Busulfan is a major component of chemotherapy conditioning in hematopoietic cell
      transplantation (HCT). This alkylating agent is highly toxic at myeloablative
      doses, exposing HCT patients to risks of mortality. Non-myeloablative (NMA) and
      reduced-intensity conditioning (RIC) using busulfan have shown impaired toxicity.
      However, the toxicity of NMA/RIC in the digestive tract is poorly described. This
      study aimed to characterize the mucositis in the oral cavity (OM),
      oropharynx/esophagus, and gastrointestinal tract derived from conditionings with
      myeloablative and non-myeloablative doses of busulfan. We retrospectively
      retrieved clinical data of HCT patients (n = 100) who underwent myeloablative
      conditioning (MAC) or NMA/RIC with busulfan. Frequency and time duration of
      mucositis in the oral cavity and oropharynx/esophagus, diarrhea, and prescription
      of total parenteral nutrition (TPN) and opioids were also collected. OM severity
      (p = 0.009) and time duration of mucositis in oropharynx/esophagus (p = 0.022)
      were frequently higher in MAC than NMA/RIC. A myeloablative dose of busulfan was
      a risk factor for OM grade >= 2 (OR = 4.8, p = 0.002) and for mucositis in
      oropharynx/esophagus >= 5 days (OR = 2.64, p = 0.035). A longer duration of
      mucositis in the oropharynx/esophagus was also associated with an increase in the
      prescription of opioids (OR = 7.10, p < 0.001).Overall survival (OS) in MAC was
      significantly higher than that in NMA/RIC (p = 0.017). No variables related to
      mucositis interfere significantly in OS. In conclusion, myelosuppression in
      busulfan-based regimens are predisposed to a high risk for severe OM and to
      prolonged mucositis in the oropharynx/esophagus.

PMID- 30109489
TI  - Sexual health in cancer: the results of a survey exploring practices, attitudes,
      knowledge, communication, and professional interactions in oncology healthcare
      providers.
AB  - PURPOSE: To assess, focusing on population of healthcare professionals providing
      oncosexology care to men with cancer, clinical practice, attitudes, knowledge,
      communication, and professional interaction. METHODS: We performed a descriptive
      cross-sectional study with an online self-administered e-questionnaire addressed
      to all medical, paramedical, or administrative professionals attending the 4th
      "Cancer, Sexuality and Fertility" Meeting in Toulouse, France. Their
      participation was voluntary and totally anonymous. RESULTS: The 165 respondents
      comprised 44% of physicians, 47% of paramedics, and 9% of other health
      professionals in oncology, from all French regions. Paramedics were significantly
      younger than physicians (p = .006). One third of respondents were degreed in
      sexology, but 75.8% were in demand of oncosexology-specific trainings,
      particularly paramedics (p = .029). Regarding the oncosexology network,
      respondents declared being linked to organ specialists (56.8%), psychologists
      (49.5%), oncologists (47.4%), nurses (31.5%), radiation therapists (27.4%), and
      general practitioners (25.3%). Compared to paramedics, physicians were more
      likely to be engaged in oncosexology care (p = .039) and couple counseling (p =
      .005), but the proportions of counseled patients or couple were identical (p =
      .430 and p = .252, respectively). Overall, 90% of respondents reported discussing
      sexuality issues with patients. Regarding the time for discussion, physicians
      reported communicating more at cancer announcement (p = .004) or after treatments
      (p = .015), while more paramedics reported discussing at another time (p = .005).
      Regarding the place for discussion, paramedics more frequently reported talking
      about sexuality in the hospital room (p = .001) or during a specific consult (p =
      .007). CONCLUSIONS: Results emphasize various levels for improving existing
      oncosexology care, such as developing oncosexology-specific educational and
      practical training programs, particularly for paramedics; consolidating
      information, counseling, and therapeutic education with formal procedures like
      implementing medical and paramedical "oncosexology moments," or strengthening the
      community-hospital networks, from diagnosis to survivorship.

PMID- 30109491
TI  - Single-axon tracing of the corticosubthalamic hyperdirect pathway in primates.
AB  - Individual axons that form the hyperdirect pathway in Macaca fascicularis were
      visualized following microiontophoretic injections of biotinylated dextran amine
      in layer V of the primary motor cortex (M1). Twenty-eight singly labeled axons
      were reconstructed in 3D from serial sections. The M1 innervation of the
      subthalamic nucleus (STN) arises essentially from collaterals of long-ranged
      corticofugal axons en route to lower brainstem regions. Typically, after leaving
      M1, these large caliber axons (2-3 um) enter the internal capsule and travel
      between caudate nucleus and putamen without providing any collateral to the
      striatum. More ventrally, they emit a thin collateral (0.5-1.5 um) that runs
      lateromedially within the dorsal region of the STN, providing boutons en passant
      in the sensorimotor territory of the nucleus. In some cases, the medial tip of
      the collateral enters the lenticular fasciculus dorsally and yields a few beaded
      axonal branches in the zona incerta. In other cases, the collateral runs caudally
      and innervates the ventrolateral region of the red nucleus where large axon
      varicosities (up to 1.7 um in diameter) are observed, many displaying perisomatic
      arrangements. Our ultrastructural analysis reveals a high synaptic incidence
      (141%) of cortical VGluT1-immunoreactive axon varicosities on distal dendrites of
      STN neurons, and on various afferent axons. Our single-axon reconstructions
      demonstrate that the so-called hyperdirect pathway derives essentially from
      collaterals of long-ranged corticofugal axons that are rarely exclusively devoted
      to the STN, as they also innervate the red nucleus and/or the zona incerta.

PMID- 30109492
TI  - Immediate early gene expression related to learning and retention of a visual
      discrimination task in bamboo sharks (Chiloscyllium griseum).
AB  - Using the expression of the immediate early gene (IEG) egr-1 as a neuronal
      activity marker, brain regions potentially involved in learning and long-term
      memory functions in the grey bamboo shark were assessed with respect to selected
      visual discrimination abilities. Immunocytochemistry revealed a significant up
      regulation of egr-1 expression levels in a small region of the telencephalon of
      all trained sharks (i.e., 'early' and 'late learners', 'recallers') when compared
      to three control groups (i.e., 'controls', 'undisturbed swimmers', 'constant
      movers'). There was also a well-defined difference in egr-1 expression patterns
      between the three control groups. Additionally, some staining was observed in
      diencephalic and mesencephalic sections; however, staining here was weak and
      occurred only irregularly within and between groups. Therefore, it could have
      either resulted from unintentional cognitive or non-cognitive inducements (i.e.,
      relating to the mental processes of perception, learning, memory, and judgment,
      as contrasted with emotional and volitional processes) rather than being a
      training effect. Present findings emphasize a relationship between the training
      conditions and the corresponding egr-1 expression levels found in the
      telencephalon of Chiloscyllium griseum. Results suggest important similarities in
      the neuronal plasticity and activity-dependent IEG expression of the elasmobranch
      brain with other vertebrate groups. The presence of the egr-1 gene seems to be
      evolutionarily conserved and may therefore be particularly useful for identifying
      functional neural responses within this group.

PMID- 30109490
TI  - Claustrum circuit components for top-down input processing and cortical
      broadcast.
AB  - Anterior cingulate cortex (ACC) input to the claustrum is required for top-down
      cognitive control of action. By virtue of its widespread cortical connectivity,
      the claustrum is anatomically situated to process and broadcast top-down signals
      from ACC to downstream cortices. To gain a deeper understanding of claustrum
      processing mechanisms, it is first critical to identify the projection neuron
      subtypes within claustrum, the intrinsic and extrinsic components regulating
      their firing, and the differential innervation of cortex by projection neuron
      subtypes. To this end, we used whole-cell patch-clamp electrophysiology in adult
      mouse brain slices to distinguish two spiny projection neuron subtypes in
      claustrum, referred to as type I and II neurons, and three aspiny interneuron
      subtypes, referred to as type III, IV, and V neurons. In response to optogenetic
      ACC afferent stimulation, type II neurons preferentially burst fire relative to
      type I neurons. This burst firing is calcium-dependent and is optimized by
      voltage-gated potassium channels. Finally, we find that visual cortices, parietal
      association cortex, and ACC receive input from type I and II neurons in differing
      proportions. These data reveal the diversity of claustrum neurons and mechanisms
      by which claustrum processes ACC command for spatiotemporal coordination of the
      cerebral cortex.

PMID- 30109493
TI  - The Use of Two Bifidobacterium Strains Enhanced Growth Performance and Nutrient
      Utilization of Rainbow Trout (Oncorhynchus mykiss) Fry.
AB  - This study aims to evaluate the effects of Bifidobacterium animalis PTCC-1631 and
      Bifidobacterium lactis PTCC-1736 on growth, nutrient digestibility, carcass
      composition, and intestinal microbiota of Oncorhynchus mykiss fry, which had
      initial body weights of 0.58 +/- 0.19 g. Four iso-nitrogenous diets with
      probiotics, namely T1 (1 * 107 CFU g-1), T2 (2 * 107 CFU g-1), T3 (3 * 107 CFU g
      1), and control without probiotics were obtained. Total 480 fish were randomly
      divided in four treatments (three experimental treatments and a control), each
      with 4 replicates including 16 tanks each filled with 15 L-1 of water (water
      exchange rate of 2 L min-1 and aerated with air stone) with a density of 2 fry L
      1. The water mean temperature was 17.66 +/- 1.33  degrees C, and the mean pH
      value was 7.63 +/- 0.08. After eight weeks of the experiment T1 that fed with a
      diet contained the lowest bacterial concentration showed higher growth, nutrient
      utilization, digestibility, and lower feed conversion ratio (P < 0.05) in
      comparison with T2, T3, and the control. Also, the highest count of lactobacillus
      bacteria was observed in T1 that was fed with a diet containing the lowest
      probiotic. The lowest concentration of Bifidobacterium strains in this study
      induced better growth and increased digestion and nutrient utilization in trout
      fry.

PMID- 30109494
TI  - Targeting the organ-specific adiposity.

PMID- 30109495
TI  - Precision/personalized aneurysm treatment in era of increasing options.

PMID- 30109496
TI  - Robotics assistance in neurosurgery-improving the outcome for our patients.

PMID- 30109497
TI  - One-year outcome of patients with posttraumatic hydrocephalus treated by
      lumboperitoneal shunt: an observational study from China.
AB  - BACKGROUND: Lumboperitoneal shunt (LPS) attracts increasing number of research
      interest in the treatment of hydrocephalus due to minimal invasiveness. However,
      the outcome of LPS-treated posttraumatic hydrocephalus (PTH) is poorly learnt,
      remaining unknown to date. METHODS: We retrospectively analyzed adult patients
      with PTH treated by LPS in our department between May 2013 and Apr 2017. Baseline
      characteristics, preoperative clinical features, symptomatic and imageologic
      improvement, and postoperative complications were synchronously investigated. All
      patients were followed up to 1 year after LPS to determine the shunt outcome and
      quality of life. Furthermore, the Kaplan-Meier curve was drawn and binary
      logistic regression analysis was used to identify the possible predictive factors
      of shunt failure. RESULTS: Thirty-eight eligible patients were included in our
      study. Five days after LPS, chronic hydrocephalus scores (CHS; 10.26 +/- 5.17 vs
      5.21 +/- 3.75; P < 0.001) and Evans index (0.36 +/- 0.06 vs 0.28 +/- 0.06; P <
      0.001) were significantly improved with statistical difference. The overall
      incidence of complications was 50% (19 patients) while hydrocephalus-associated
      death or shunt failure was not observed immediately after LPS. According to the 1
      year follow-up, most of the patients obtained good prognosis while 16 patients
      (42.1%) were failed, including 15 patients (39.5%) underwent shunt revision and
      one patient (2.6%) was dead ascribing to shunt malfunction. However, we failed to
      screen out any factors contributing to LPS failure. CONCLUSION: To sum up, we
      have, for the first time, demonstrated that LPS could be a potential option to
      treat PTH.

PMID- 30109498
TI  - Mixed gangliocytoma-pituitary adenoma in the sellar region: a large-scale single
      center experience.
AB  - BACKGROUND: Mixed gangliocytoma-pituitary adenoma is an extremely rare tumor
      occurring in the sellar region, histologically composed of both gangliocytic and
      pituitary adenomatous architectures. The histogenesis of these tumors remains
      unknown, and the diagnosis, treatment, and prognosis are yet to be fully
      understood. METHODS: We retrospectively reviewed the clinical, radiological, and
      histopathological profiles from a series of 20 patients with sellar mixed
      gangliocytoma-pituitary adenomas. All patients underwent surgical tumorectomy via
      an endoscopic or microscopic transsphenoidal approach. Perioperative magnetic
      resonance imaging (MRI) and computed tomography (CT) data were reviewed.
      Immunohistochemical stains and electron microscopy examination were performed.
      Follow-up outcomes were presented. RESULTS: This case series consisted of 13
      females and seven males (age range, 20-59 years; mean age, 42.3 +/- 11.2 years).
      Preoperative endocrine examination showed elevated growth hormone (GH) in nine
      patients and hyperprolactinemia in eight patients. The tumors were positive for
      GH in 15 cases, prolactin in 13 cases, adrenocorticotropic hormone in three
      cases, and thyroid-stimulating hormone in one case. Gross total resection was
      achieved in 15 patients, and subtotal resection in five patients. During an
      average follow-up period of 42.5 +/- 29.0 months, no recurrence was noted.
      CONCLUSIONS: The clinical and neuroimaging features of sellar mixed gangliocytoma
      pituitary adenomas are non-specific, and invasion into the cavernous sinus is
      common. Surgical resection via a transsphenoidal approach is the preferred
      treatment, and the surgical outcomes are favorable. Moreover, our
      histopathological findings are more likely to support the theory that mixed
      gangliocytoma-pituitary adenoma originates from the neuronal transdifferentiation
      of adenomatous cells.

PMID- 30109499
TI  - Self-harm and suicidal behaviour among incarcerated adults in the Australian
      Capital Territory.
AB  - BACKGROUND: Suicide is the leading cause of death in prisons worldwide. Improved
      understanding of the factors associated with suicide is necessary to inform
      targeted suicide prevention and interventions. Here we aim to (a) document the
      prevalence of suicide attempts, suicidal ideation, self-harm, and mental
      disorder; and (b) identify demographic, mental health, and criminal justice
      correlates of suicidal ideation, in a sample of incarcerated adults in Australia.
      METHODS: Data were obtained from the 2016 Detainee Health and Wellbeing Survey
      conducted in the Alexander Maconochie Centre, the Australian Capital Territory's
      only adult prison. Interviews with 98 incarcerated adults were conducted in
      October 2016. Descriptive statistics were calculated for all measures. Crude
      differences between participants who reported experiencing suicidal ideation in
      their lifetime and those who did not were compared using Fisher's exact test.
      RESULTS: Nearly half of the participants (48%, n = 47) reported lifetime suicidal
      ideation and 31% (n = 30) reported attempting suicide at some point in their
      lives. Eighteen participants (18%) reported a lifetime history of having engaged
      in self-harm. Factors significantly associated with suicidal ideation included
      lifetime history of mental disorder, self-harm, experiencing a drug overdose, and
      being hospitalized in the past 12 months. CONCLUSION: The burden of suicidal
      ideation and prior suicide attempts among people in prison is substantial.
      Incarceration is a pivotal opportunity to identify people with a history of
      mental health problems and target interventions aimed at reducing adverse
      outcomes including suicide mortality.

PMID- 30109500
TI  - MiRNAs and their interplay with PI3K/AKT/mTOR pathway in ovarian cancer cells: a
      potential role in platinum resistance.
AB  - Ovarian cancer is a leading cause of death among gynecologic malignancies. This
      disappointing prognosis is closely related to intrinsic or acquired resistance to
      conventional platinum-based chemotherapy, which can affect a third of patients.
      As such, investigating relevant molecular targets is crucial in the fight against
      this disease. So far, many mutations involved in ovarian cancer pathogenesis have
      been identified. Among them, a few pathways were implicated. One such pathway is
      the P13K/AKT/mTOR with abnormalities found in many cases. This pathway is
      considered to have an instrumental role in proliferation, migration, invasion
      and, more recently, in chemotherapy resistance. Many miRNAs have been found to
      influence P13K/AKT/mTOR pathway with different potential role in tumor genesis
      and ovarian cancer behaviour. In particular, their biological function was
      recently investigated as regards chemoresistance, therefore, leading to the
      identification of potential specific indirect biomarker of platinum sensitivity
      in ovarian cancer.

PMID- 30109502
TI  - A Contemporary Perspective on the Management of Post-Craniotomy Headache and
      Pain.
AB  - PURPOSE OF REVIEW: This article discusses the etiology and management of post
      craniotomy headache and pain. A review of available as well as investigatory
      treatment modalities is offered, followed by suggestions for optimal management
      of post-craniotomy headache. RECENT FINDINGS: There is a dearth of evidence-based
      practice regarding the differential diagnosis, natural history, and management of
      post-craniotomy headache. The etiology of post-craniotomy headache is typically
      multifactorial, with patients' medical history, type of craniotomy, and
      perioperative management all playing a role. Post-craniotomy headaches are often
      undertreated, yet available evidence supports a multimodal approach for both
      prophylaxis and management. Many therapeutic techniques that aim to treat or
      prevent post-craniotomy headache require more robust validation than clinical
      evidence currently imparts. Pre- and intraoperative locoregional anesthesia
      should be the mainstay of prophylaxis; the role of opiates co-administered with
      analgesics, corticosteroids, and antiepileptic therapy in the acute perioperative
      phase is of paramount importance. Treatment of chronic PCH is less well-defined
      but should involve trials of analgesic, antineuropathic, and antiepileptic
      medications before enlisting experimental treatments. Comorbid psychiatric,
      musculoskeletal, or seizure disorders should be managed distinctly from post
      craniotomy headaches. In patients failing all extant therapies, experimental
      approaches should be considered. These include subanesthetic ketamine infusion or
      surgical site injection with local anesthetics, corticosteroids, or botulinum
      toxin. Post-craniotomy headache is a complex phenomenon with many underutilized
      treatment options available, and many more under investigation. Nonetheless,
      further research is required to differentiate the efficacy of contemporary
      treatment strategies and to elucidate the applicability of novel therapies.

PMID- 30109501
TI  - Platinum-based concurrent chemotherapy remains the optimal regimen for
      nasopharyngeal carcinoma: a large institutional-based cohort study from an
      endemic area.
AB  - PURPOSE: To retrospectively investigate the optimal regimen of concurrent
      chemotherapy for nasopharyngeal carcinoma (NPC) by comparing clinical outcomes of
      patients who received platinum-based and non-platinum-based concurrent
      chemoradiotherapy (CCRT) regimens. METHODS: Based on a prospectively maintained
      database from 1998 to 2013 in an endemic area, a total of 4608 newly diagnosed,
      biopsy-proven, and non-disseminated NPC patients were identified and allocated
      into three cohorts based on concurrent chemotherapy regimens: cisplatin-based
      (CP) chemotherapy cohort, other platinum-based (OP) chemotherapy cohort, and non
      platinum-based (NP) chemotherapy cohort. Overall survival (OS) and disease-free
      survival (DFS) were estimated using the Cox proportional hazards model and
      propensity score analysis of treatment using an inverse probability weighting
      model (PSA/IPTW). Finally, sensitivity analysis estimated the effects of
      potential unmeasured confounders. RESULTS: The median follow-up time was 68.5
      months (range 2-194 months). The multivariate Cox model showed that NP regimens
      were significantly related with worse survival compared with CP or OP regimens
      (OS: HR 1.51, 95% CI 1.16-2.00, P = 0.002; HR 1.68, 95% CI 1.24-2.27, P = 0.001;
      DFS: HR 1.31, 95% CI 1.03-1.66, P = 0.031; HR 1.50, 95% CI 1.14-1.97, P = 0.004,
      respectively). Meanwhile, no significant survival difference was found between OP
      and CP regimens. The PSA/IPTW method, CCRT-specific and III-IVB NPC cohort
      subgroup analysis showed similar results. Sensitivity analysis confirmed the
      robustness of our results. CONCLUSIONS: Platinum-based concurrent chemotherapy,
      including both CP and OP regimens, yields better survival benefits for non
      metastatic NPC patients than the NP regimen and remains the optimal regimen for
      these patients.

PMID- 30109503
TI  - Hamstring stiffness pattern during contraction in healthy individuals: analysis
      by ultrasound-based shear wave elastography.
AB  - PURPOSE: To assess the stiffness of hamstring muscles during isometric
      contractions in healthy individuals, using ultrasound-based shear wave
      elastography to (1) determine the intra- and inter-day assessment repeatability,
      (2) characterize the stiffness of semitendinosus (ST) and biceps femoris long
      head (BFlh) along the contraction intensity, and (3) characterize stiffness
      distribution among the hamstring muscles and inter-limb symmetry. METHODS: Two
      experiments were conducted. In experiment I (n = 12), the intra-day repeatability
      in assessing the BFlh and ST stiffness were determined at intensities between 10
      60% of maximal voluntary isometric contraction (MVIC) in a single session. In
      experiment II (n = 11), the stiffness of the hamstring muscles of both thighs was
      assessed at 20% of MVIC in the first session; and retested (for one randomly
      chosen thigh) in a second session. Isometric contraction of knee flexors was
      performed with the knee flexed at 30 degrees  and with the hip in a neutral
      position. RESULTS: Moderate-to-very-high intra- and inter-day repeatability was
      found (ICC = 0.69-0.93). The BFlh/ST stiffness ratio increased with contraction
      intensity. At 20% of MVIC, the ST showed the highest stiffness among the
      hamstring muscles (p < 0.02), with no differences between the remaining hamstring
      muscles (p > 0.474). No differences were found between limbs (p = 0.12).
      CONCLUSIONS: The stiffness distribution among the hamstring muscles during
      submaximal isometric contractions is heterogeneous, but symmetric between limbs,
      and changes depending on the contraction intensity. Shear wave elastography is a
      reliable tool to assess the stiffness of hamstring muscles during contraction.

PMID- 30109504
TI  - The value of radiography in the follow-up of extremity fractures: a systematic
      review.
AB  - BACKGROUND: The added value of routine radiography in the follow-up of extremity
      fractures is unclear. The aim of this systematic review was to create an overview
      of radiography use in extremity fracture care and the consequences of these
      radiographs for the treatment of patients with these fractures. MATERIALS AND
      METHODS: Studies were included if they reported on the use of radiography in the
      follow-up of extremity fractures and on its influence on treatment strategy,
      clinical outcome, or complications. A comprehensive search of electronic
      databases (i.e., PubMed, Embase, and Cochrane) was performed to identify relevant
      studies. Methodological quality was assessed with the Newcastle-Ottawa scale for
      cohort studies. Level of evidence was assessed using GRADE. The search, quality
      appraisal, and data extraction were performed independently by two researchers.
      RESULTS: Eleven studies were included. All studies were retrospective cohorts. Of
      these, only two used a comparative design. Two of the included studies described
      fractures of both the upper and lower extremities, four studies concerned
      fractures of the lower extremity only, and five studies focused on fractures of
      the upper extremity. Pooling of data was not performed because of clinical
      heterogeneity. Eight studies reported on a change in treatment strategy related
      to radiography. Percentages ranged from 0 to 2.6%. The overall results indicated
      that radiographs in the follow-up of extremity fractures seldom alter treatment
      strategy, that the vast majority of follow-up radiographs are obtained without a
      clinical indication and that detection of a complication on a radiograph, in the
      absence of clinical symptoms, is unlikely. All included studies were regarded of
      a 'very low' level using GRADE. CONCLUSIONS: Based on current literature, the
      added value of routine radiography in the follow-up of extremity fractures seems
      limited. Results, however, should be interpreted with care, considering that
      available evidence is of a low level.

PMID- 30109505
TI  - Variation and relationship of THMs between tap water and finished water in
      Yancheng City, China.
AB  - In this paper, spatial and temporal variations of trihalomethane (THM)
      concentrations were analyzed including chloroform trichloromethane (TCM),
      bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane
      (TBM) in Yancheng City in Jiangsu Province, China. The water samples were
      collected monthly from January 2014 to January 2017 from four tap water sampling
      sites (S1, S2, S3, and S4) and two finished water sampling sites (WTP1 and WTP2)
      for THM analysis. The results showed that the mean concentrations during the
      study period for TCM, BDCM, DBCM, and TBM were 7, 15.9, 21, and 10.4 MUg/L in tap
      water samples and 3.2, 17.2, 22.7, and 10 MUg/L in finished water samples, which
      indicated that brominated THM concentrations were higher than chlorinated THM
      concentrations. The results of spatial analysis showed that THM concentrations in
      WTP1 were related to those in S1 and S4 and THM concentrations in WTP2 were
      related to those in S2 and S3. The concentrations of TCM, BDCM, and TBM have
      significant spatial variance, while DBCM and THM concentrations do not. The
      temporal analysis revealed that the highest THM concentration occurred in April,
      both in tap water and in finished water, which was also shown by temporal cluster
      analysis. The lowest THM concentration occurred in seasons with relatively lower
      temperature in all sampling sites. The results provide important information for
      environmental protection agencies and health care centers with emphasis on months
      with higher THM risk.

PMID- 30109506
TI  - Trend and Outcomes of Direct Transcatheter Aortic Valve Replacement from a Single
      Center Experience.
AB  - INTRODUCTION: When transcatheter aortic valve replacement (TAVR) was introduced,
      pre-implantation balloon aortic valvuloplasty (BAV) was a routine part of the
      procedure. Smaller device profiles have resulted in selective use of BAV;
      however, there is a paucity of data about the trend in use of direct TAVR and the
      safety of this strategy. METHODS: All patients who underwent TAVR at a Veterans
      Affairs Medical Center from September 2013 to November 2016 were included in this
      retrospective analysis. We reviewed angiography films and verified with procedure
      reports to assess if direct TAVR was performed. Troponin T was assessed within 72
      h after the TAVR. Multivariate analysis examined the association between direct
      TAVR and periprocedural myocardial infarction (MI) or 1-year mortality. RESULTS:
      Overall, 207 patients were available for analysis. The mean follow-up was 13.3
      months. A balloon-expandable valve was used 93.2% of the time, and 35.3% of
      patients were treated with conscious sedation. Periprocedural MI or 1-year
      mortality occurred in 12.5% of the direct TAVR group versus 18.3% of the pre
      implantation BAV group (p = 0.30). After controlling for potential confounding
      variables, direct TAVR was not associated with periprocedural MI or 1-year
      mortality. CONCLUSIONS: Direct TAVR appears to be safe and is not associated with
      periprocedural MI or 1-year mortality. With current generation devices, this
      strategy can be considered for most patients undergoing TAVR.

PMID- 30109507
TI  - Adherent Intrapericardial Teratoma: A Case Report.
AB  - Intrapericardial teratomas are rare tumours arising from all three germinal
      layers. They are mostly benign, but can lead to life-threatening complications
      such as cardiac tamponade in newborns, so surgical excision of the tumour should
      be done as early as possible once the diagnosis is made. We report a neonate
      diagnosed with a large intrapericardial teratoma, managed surgically with the
      help of cardiopulmonary bypass.

PMID- 30109508
TI  - An Intelligent Model for Blood Vessel Segmentation in Diagnosing DR Using CNN.
AB  - Diabetic retinopathy (DR) is an eye disease, which affects the people who are all
      having the diabetes for more than 10 years. The ophthalmologist identifies when
      the dilated eye exam causes severe in any one of the following deviations in the
      retina: changes in blood vessels, leaking blood vessels, newly grown blood
      vessels, swelling of the macula, changes in the lens, and damages to the nerve
      tissue. It can eventually lead to vision loss. The early detection of DR prevents
      the cause of blindness. In this paper, we propose the retinal image segmentation
      and extraction of blood vessels by morphological processing, thresholding, edge
      detection, and adaptive histogram equalization. For the automatic diagnosis of DR
      from the fundus image, we also developed a network with the convolutional neural
      network architecture for accurately classifying its severity. By using high-end
      graphical processor unit (GPU), we trained this network on the publicly available
      dataset such as DRIVE, DIARETDB0, and DIARETDB1_v1, and the images collected from
      the Aravind Eye Hospital, Coimbatore, India. Our proposed CNN achieves a
      sensitivity of 98%, a specificity of 93%, and an accuracy of 96.9% containing a
      database of 854 images.

PMID- 30109510
TI  - Is it best to reFOCUS on basic echocardiography in the emergency department?

PMID- 30109509
TI  - Inflammatory dietary pattern and risk of developing rheumatoid arthritis in
      women.
AB  - Our objective was to investigate whether a dietary pattern derived using
      inflammatory biomarkers is associated with rheumatoid arthritis (RA) risk. We
      prospectively followed 79,988 women in the Nurses' Health Study (NHS, 1984-2014)
      and 93,572 women in the NHSII (1991-2013); incident RA was confirmed by medical
      records. Food frequency questionnaires (FFQ) were completed at baseline and
      approximately every 4 years. Inflammatory dietary pattern was assessed from FFQ
      data using the Empirical Dietary Inflammatory Pattern (EDIP), including 18 anti
      /pro-inflammatory food/beverage groups weighted by correlations with plasma
      inflammatory biomarkers (interleukin-6, C-reactive protein, and tumor necrosis
      factor-alpha receptor 2). We investigated associations between EDIP and RA using
      Cox regression. We identified 1185 incident RA cases over 4,425,434 person-years.
      EDIP was not associated with overall RA risk (p trend = 0.21 across EDIP
      quartiles). Among women <= 55 years, increasing EDIP was associated with
      increased overall RA risk; HRs (95% CIs) across EDIP quartiles were 1.00
      (reference), 1.14 (0.86-1.51), 1.35 (1.03-1.77), and 1.38 (1.05-1.83; p for trend
      = 0.01). Adjusting for BMI attenuated this association. Increasing EDIP was
      associated with increased seropositive RA risk among women <= 55 years (p for
      trend = 0.04). There was no association between EDIP and RA among women > 55
      years (EDIP-age interaction, p = 0.03). An inflammatory dietary pattern was
      associated with increased seropositive RA risk with onset <= 55 years old, and
      this association may be partially mediated through BMI.

PMID- 30109512
TI  - Natural speciation of nickel at the micrometer scale in serpentine (ultramafic)
      topsoils using microfocused X-ray fluorescence, diffraction, and absorption.
AB  - Serpentine soils and ultramafic laterites develop over ultramafic bedrock and are
      important geological materials from environmental, geochemical, and industrial
      standpoints. They have naturally elevated concentrations of trace metals, such as
      Ni, Cr, and Co, and also high levels of Fe and Mg. Minerals host these trace
      metals and influence metal mobility. Ni in particular is an important trace metal
      in these soils, and the objective of this research was to use microscale (u)
      techniques to identify naturally occurring minerals that contain Ni and Ni
      correlations with other trace metals, such as Fe, Mn, and Cr. Synchrotron based u
      XRF, u-XRD, and u-XAS were used. Ni was often located in the octahedral layer of
      serpentine minerals, such as lizardite, and in other layered phyllosilicate
      minerals with similar octahedral structure, such as chlorite group minerals
      including clinochlore and chamosite. Ni was also present in goethite, hematite,
      magnetite, and ferrihydrite. Goethite was present with lizardite and antigorite
      on the micrometer scale. Lizardite integrated both Ni and Mn simultaneously in
      its octahedral layer. Enstatite, pargasite, chamosite, phlogopite, and forsterite
      incorporated various amounts of Ni and Fe over the micrometer spatial scale. Ni
      content increased six to seven times within the same 500 um u-XRD transect on
      chamosite and phlogopite. Data are shown down to an 8 um spatial scale. Ni was
      not associated with chromite or zincochromite particles. Ni often correlated with
      Fe and Mn, and generally did not correlate with Cr, Zn, Ca, or K in u-XRF maps. A
      split shoulder feature in the u-XAS data at 8400 eV (3.7 A-1 in k-space) is
      highly correlated (94% of averaged LCF results) to Ni located in the octahedral
      sheet of layered phyllosilicate minerals, such as serpentine and chlorite-group
      minerals. A comparison of bulk-XAS LCF to averaged u-XAS LCF results showed good
      representation of the bulk soil via the u-XAS technique for two of the three
      soils. In the locations analyzed by u-XAS, average Ni speciation was dominated by
      layered phyllosilicate and serpentine minerals (76%), iron oxides (18%), and
      manganese oxides (9%). In the locations analyzed by u-XRD, average Ni speciation
      was dominated by layered phyllosilicate, serpentine, and ultramafic-related
      minerals (71%) and iron oxides (17%), illustrating the complementary nature of
      these two methods.

PMID- 30109511
TI  - Induction Therapy for Lupus Nephritis: the Highlights.
AB  - PURPOSE OF REVIEW: Lupus nephritis is a frequent complication of systemic lupus
      erythematosus and is more common and severe in children. This is a disease of the
      immune system characterized by T cell, B cell, and complement activation, as well
      as immune complex formation and deposition. The introduction of steroids and
      later cyclophosphamide transformed lupus nephritis from a fatal to a treatable
      condition. However, the standard therapies currently used for treatment carry
      significant toxicity and chronic kidney disease still remains a far too frequent
      outcome. To address these issues, we will review current and emerging induction
      therapies in LN. RECENT FINDINGS: Several clinical trials have been undertaken to
      test more effective and safer drugs, often targeting mechanistic disease
      pathways. At present, it is difficult to identify an induction regimen that is
      more effective and less toxic than the standard of care; however, we believe
      continuing efforts in drug development will bring breakthrough agents to clinics.

PMID- 30109513
TI  - 8-Hydroxyquinoline Functionalized Graphene Oxide: an Efficient Fluorescent
      Nanosensor for Zn2+ in Aqueous Media.
AB  - A nanosensor, based on 8-hydroxyquinoline functionalized graphene oxide, was
      developed for the fluorescence detection of Zn2+. It showed high selectivity and
      sensitivity for Zn2+ion in aqueous solution over other metal ions such as Li+,
      Na+, Ca2+, Mg2+, Al3+, Cd2+, Co2+, Cu2+, Hg2+, Ni2+, Pb2+, Fe2+, Fe3+and Cr3+.
      Due to the linearity of the emission intensity toward Zn2+ concentration,
      fluorescent technique could be used for the detection of Zn2+ ion even at very
      low concentrations.

PMID- 30109514
TI  - Rheumatic Manifestations of Haemoglobinopathies.
AB  - PURPOSE OF THE REVIEW: To provide a clinically useful literature review on the
      rheumatic manifestations of haemoglobinopathies, critically analysing the
      literature from the past 5 years. RECENT FINDINGS: There are limited new data to
      guide the management of rheumatic manifestations of haemoglobinopathies. Data
      further confirm the wide spectrum of potential rheumatic/MSK involvement in
      haemoglobinopathies, which poses both a diagnostic and therapeutic challenge.
      Inflammatory arthritis may be more common than previously believed. Steroid
      therapy by any route of administration can provocate a potential life-threatening
      vaso-occlusive crisis. Vitamin D deficiency is common. There are limited data to
      guide the drug treatment of reduced bone density in haemoglobinopathies. There
      have been a number of studies examining pain in sickle cell anaemia. Plasma
      levels of Klotho may represent a novel biomarker in patients with beta
      Thalassemia. There are little new data on the rheumatic manifestations in
      haemoglobinopathies and future high-quality research is needed.

PMID- 30109515
TI  - Neuroactive Steroids and Sex-Dimorphic Nervous Damage Induced by Diabetes
      Mellitus.
AB  - Diabetes mellitus is a metabolic disease where improper glycaemic control may
      induce severe complications in different organs. In this review, we will discuss
      alterations occurring in peripheral and central nervous system of patients with
      type 1 (i.e., insulin dependent diabetes mellitus,) or type 2 diabetes (i.e., non
      insulin dependent diabetes mellitus), as well as related experimental models. A
      particular focus will be on the role exerted by neuroactive steroids (i.e.,
      important regulators of nervous functions) in the nervous damage induced by
      diabetes. Indeed, the nervous levels of these molecules are affected by the
      pathology and, in agreement, their neuroprotective effects have been reported.
      Interestingly, the sex is another important variable. As discussed, nervous
      diabetic complications show sex dimorphic features in term of incidence,
      functional outcomes and neuroactive steroid levels. Therefore, these features
      represent an interesting background for possible sex-oriented therapies with
      neuroactive steroids aimed to counteract nervous damage observed in diabetic
      pathology.

PMID- 30109518
TI  - Evolving connectionist systems (ECoSs): a new approach for modeling daily
      reference evapotranspiration (ET0).
AB  - Over the last few years, the uses of artificial intelligence techniques (AI) for
      modeling daily reference evapotranspiration (ET0) have become more popular and a
      considerable amount of models were successfully applied to the problem.
      Therefore, in the present paper, we propose a new evolving connectionist (ECoS)
      approaches for modeling daily reference evapotranspiration (ET0) in the
      Mediterranean region of Algeria. Three ECoS models, namely, (i) the off-line
      dynamic evolving neural-fuzzy inference system called DEFNIS_OF, (ii) the on-line
      dynamic evolving neural-fuzzy inference system called DEFNIS_ON, and (iii) the
      evolving fuzzy neural network called (EFuNN), were statistically compared using
      the root mean square error (RMSE), the mean absolute error (MAE), the coefficient
      of correlation (R), and the Nash-Sutcliffe efficiency (NSE) indexes. The proposed
      approaches were applied for modeling daily ET0 using climatic variables from two
      weather stations: Algiers and Skikda, Algeria. Five well-known climatic variables
      were selected as inputs: daily maximum and minimum air temperatures (Tmax and
      Tmin), daily wind speed (WS), daily relative humidity (RH), and daily sunshine
      hours (SH). The effect of combining several climatic variables as inputs was
      evaluated, and at least six scenarios were developed and compared. The proposed
      ECoS models were compared against the reference Penman-Monteith model referred as
      "FAO-56 PM". According to the results obtained, the DEFNIS_OF1 model having Tmax,
      Tmin, WS, RH, and SH as inputs, is the best model, followed by the DEFNIS_ON1,
      and the EFuNN1 is the worst model. The R and NSE value calculated for the testing
      dataset for the Algiers and Skikda stations were (0.954, 0.910) and (0.954,
      0.905), respectively. While both DEFNIS_OF1 and DEFNIS_ON1 showed good accuracy
      and high performances, the EFuNN1 was less accurate.

PMID- 30109516
TI  - Physiological Concentrations of Zinc Have Dual Effects on P2X Myenteric Receptors
      of Guinea Pig.
AB  - We, hereby, characterize the pharmacological effects of physiological
      concentrations of Zinc on native myenteric P2X receptors from guinea-pig small
      intestine and on P2X2 isoforms present in most myenteric neurons. This is the
      first study describing opposite effects of Zinc on these P2X receptors. It was
      not possible to determine whether both effects were concentration dependent, yet
      the inhibitory effect was mediated by competitive antagonism and was
      concentration dependent. The potentiating effect appears to be mediated by
      allosteric changes induced by Zinc on P2X myenteric channels, which is more
      frequently observed in myenteric neurons with low zinc concentrations. In P2X2-1
      and P2X2-2 variants, the inhibitory effect is more common than in P2X myenteric
      channels. However, in the variants, the potentiatory effect is of equal magnitude
      as the inhibitory effect. Inhibitory and potentiatory effects are likely mediated
      by different binding sites that appear to be present on both P2X2 variants. In
      conclusion, in myenteric native P2X receptors, Zinc has quantitatively different
      pharmacological effects compared to those observed on homomeric channels: P2X2-1
      and P2X2-2. Potentiatory and inhibitory Zinc effects upon these receptors are
      mediated by two different binding sites. All our data suggest that myenteric P2X
      receptors have a more complex pharmacology than those of the recombinant P2X2
      receptors, which is likely related to other subunits known to be expressed in
      myenteric neurons. Because these dual effects occur at Zinc physiological
      concentrations, we suggest that they could be involved in physiological and
      pathological processes.

PMID- 30109519
TI  - The prognostic value of androgen receptors in breast cancer subtypes.
AB  - PURPOSE: Androgen receptor (AR) expression is frequent in breast cancer and has
      been associated with good prognosis in several studies. The present study
      investigates AR-expression in relation to molecular subtypes, clinicopathological
      features and prognosis in 1297 primary tumours and 336 paired axillary lymph node
      metastases (LNM) from two cohorts of Norwegian patients. METHODS:
      Immunohistochemistry for AR was performed on tumours previously reclassified into
      molecular subtypes using immunohistochemistry and in situ hybridisation.
      Associations between AR-expression and clinical features were studied using Chi
      square tests. Cumulative incidence of breast cancer death and Cox regression
      analyses were used to assess prognosis. RESULTS: AR-positivity was found in 78.0%
      of all cases, 84.9% of luminal and 45.1% of non-luminal tumours. The highest
      proportion of AR-positivity was found in Luminal B tumours, and the lowest in the
      Basal phenotype. Discordance in AR-status between primary tumours and lymph node
      metastases was observed in 21.4% of cases. A switch from AR- primary tumour to
      AR+ lymph node metastasis was seen in 60/72 discrepant cases. AR-expression in
      primary tumours was an independent and favourable prognostic marker (HR 0.70, 95%
      CI 0.55-0.90), particularly in the Luminal A subtype, and in grade 3 tumours.
      CONCLUSIONS: AR is an independent predictor of good prognosis in BC, particularly
      in grade 3 and Luminal A tumours. Discordant AR-expression between primary tumour
      and LNM was observed in 21.4% of cases and most often there was a switch from AR-
      primary tumour to AR+ axillary LNM.

PMID- 30109521
TI  - Synchronization and Alignment of Follow-up Examinations: a Practical and
      Educational Approach Using the DICOM Reference Coordinate System.
AB  - This work presents an approach for synchronization and alignment of Digital
      Imaging and Communications in Medicine (DICOM) series from different studies that
      allows, e.g., easier reading of follow-up examinations. The proposed concept
      developed within the DICOM's patient-based reference coordinate system allows to
      synchronize all image data of two different studies/examinations based on a
      single registration. The most suitable DICOM series for registration could be set
      as default per protocol. Necessary basics regarding the DICOM standard and the
      used mathematical transformations are presented in an educative way to allow
      straightforward implementation in Picture Archiving And Communications Systems
      (PACS) and other DICOM tools. The proposed method for alignment of DICOM images
      is potentially also useful for various scientific tasks and machine-learning
      applications.

PMID- 30109517
TI  - The degradative activity and adaptation potential of the litter-decomposing
      fungus Stropharia rugosoannulata.
AB  - The ability of the litter-decomposing basidiomycete Stropharia rugosoannulata DSM
      11372 to degrade a wide range of structurally different environmental pollutants
      such as polycyclic aromatic hydrocarbons (PAHs: phenanthrene, anthracene,
      fluorene, pyrene, and fluoranthene), synthetic anthraquinone dyes containing
      condensed aromatic rings, environmentally relevant alkylphenol and oxyethylated
      alkylphenol representatives, and oil was demonstrated within the present study.
      9,10-Anthraquinone, phenanthrene-9,10-quinone, and 9-fluorenone were identified
      as products of anthracene, phenanthrene, and fluorene degradation, respectively.
      Fungal degradation was accompanied by the production of the ligninolytic enzymes:
      laccase and Mn peroxidase, suggesting their involvement in pollutant degradation.
      Extracellular polysaccharide(s) (EPS) and emulsifying compound(s) were
      concomitantly produced. EPS composed of mannose, glucose, and galactose was
      isolated from the cultivation medium, and its effects on catalytic properties of
      purified laccase from S. rugosoannulata (the dominating ligninolytic enzyme under
      the applied conditions) were studied. A simultaneous decrease of KM and Vmax
      values observed for the enzymatic oxidation of non-phenolic (2,2-azino-bis-(3
      ethylbenzthiazoline-6-sulphonic acid) diammonium salt; ABTS) and phenolic
      compounds (2,6-dimethoxyphenol) in presence of EPS suggest an interaction of EPS
      and laccase resulting in a modulation of the catalytic performance of the enzyme,
      which has, to the best of our knowledge, not been reported before. In line with
      such a modulation, the laccase-catalyzed oxidation of natural aromatic compounds
      (veratryl alcohol, adlerol) and environmental pollutants (the alkylphenol
      representative nonylphenol, the diphenylmethane derivative bisphenol A, and the
      PAH representative anthracene) was found to be enhanced in presence of EPS. The
      relevance of such effects for real environmental processes and their implications
      remain to be investigated.

PMID- 30109522
TI  - Correction to: Cortisol Predicts Performance During Competition: Preliminary
      Results of a Field Study with Elite Adolescent Taekwondo Athletes.
AB  - The original version of this article unfortunately contained a mistake in text
      under "Subject" section. The text portions masked for peer review were
      erroneously overlooked during the later stage "[country deleted to maintain the
      integrity of the review process]" and "[organization deleted to maintain the
      integrity of the review process]" should be replaced with "German" and
      "Bundesinstitut fur Sportwissenschaft" respectively.

PMID- 30109520
TI  - Double unilateral, bilateral, and multiple mandibular fractures: an observational
      study.
AB  - PURPOSE: Double and multiple mandibular fractures are associated to high
      morbidity and functional damage. This study aimed to evaluate the characteristics
      and outcomes of double unilateral, bilateral, and multiple mandibular fractures.
      METHODS: A 7-year observational retrospective analysis was performed, and the
      injury-related data were collected from the medical records. Statistical analysis
      was performed using Fisher's exact test (p < 0.05). RESULTS: In this period, 283
      patients showed mandibular fractures. Of them, 83 (29.7%) had double or multiple
      mandibular fractures and were included in the study. Double bilateral fractures
      were more prevalent than multiple or double unilateral. Multiple fractures
      presented significant association with the combination of load-bearing and load
      sharing fixation protocols. Most cases (94.0%) applied at least one type of
      internal fixation system. However, there was a positive association between
      condylar fractures and non-surgical treatment (p < 0.01). Moreover, mandibular
      body fractures were associated with load-bearing fixation (p < 0.01). In 56
      cases, no complications were observed (67.5%). Complications were divided into
      treatment failure (10.8%) and transitory or minor complications (21.7%). There
      was no statistical association between complications and fracture pattern,
      fracture-tooth relation, and treatment modality. CONCLUSION: Double and multiple
      mandibular fractures represented almost one third of all mandibular fractures,
      and regardless to treatment protocol, there was no difference about
      complications. Moreover, although a considerable complication rate was found,
      most of them were minor or transitory.

PMID- 30109523
TI  - Tauhe multiple temporalities of deep brain stimulation (DBS) in Greece.
AB  - This contribution intends to explore patients' lived experience, with a focus on
      the temporal dimension. On the basis of a qualitative study that led me to
      interview persons with Parkinson's disease (PD), caregivers, and medical
      professionals, I develop an empirical and philosophical investigation of the
      temporalities surrounding the implementation of deep brain stimulation (DBS) in
      Greece. I raise the issue of access to DBS medical care, and show how distinct
      temporalities are implied when the patients face such a matter: that of linear
      time, linked with the medical discourse, the bureaucratic time linked to
      administrative and financial hurdles in the implementation and maintenance of
      DBS, and the technological time of the body/technology fusion. I consider
      initially the impact of technology and health care settings on the lived
      experience of patients and the enactment of multiple bodies which are
      interrelated with the social world. I then expand my analysis in order to show
      that this experience cannot be a solipsistic one, or specific to one
      physician/patient relationship. It is fully socially shaped.

PMID- 30109524
TI  - Correction to: first epicardial mapping of the left ventricle using the advisor
      TM HD grid catheter.
AB  - Figure 1 as originally published was incorrect-on the published fig. 1C there is
      no RVA catheter and the wrong figure caption was used. Figure 1 has been
      corrected along with the figure caption.

PMID- 30109526
TI  - Estimates of potential childhood lead exposure from contaminated soil using the
      USEPA IEUBK model in Melbourne, Australia.
AB  - Soils in inner city areas internationally and in Australia have been contaminated
      with lead (Pb) primarily from past emissions of Pb in petrol, deteriorating
      exterior Pb-based paints and from industry. Children can be exposed to Pb in soil
      dust through ingestion and inhalation leading to elevated blood lead levels
      (BLLs). Currently, the contribution of soil Pb to the spatial distribution of
      children's BLLs is unknown in the Melbourne metropolitan area. In this study,
      children's potential BLLs were estimated from surface soil (0-2 cm) samples
      collected at 250 locations across the Melbourne metropolitan area using the
      United States Environmental Protection Agency (USEPA) Integrated Exposure Uptake
      Biokinetic (IEUBK) model. A dataset of 250 surface soil Pb concentrations
      indicate that soil Pb concentrations are highly variable but are generally
      elevated in the central and western portions of the Melbourne metropolitan area.
      The mean, median and geometric soil Pb concentrations were 193, 110 and 108
      mg/kg, respectively. Approximately 20 and 4% of the soil samples exceeded the
      Australian HIL-A residential and HIL-C recreational soil Pb guidelines of 300 and
      600 mg/kg, respectively. The IEUBK model predicted a geometric mean BLL of 2.5 +/
      2.1 ug/dL (range: 1.3-22.5 ug/dL) in a hypothetical 24-month-old child with BLLs
      exceeding 5 and 10 ug/dL at 11.6 and 0.8% of the sampling locations,
      respectively. This study suggests children's exposure to Pb contaminated surface
      soil could potentially be associated with low-level BLLs in some locations in the
      Melbourne metropolitan area.

PMID- 30109525
TI  - Contact force-sensing catheters: performance in an ex vivo porcine heart model.
AB  - PURPOSE: Contact force (CF) catheters are useful to address proper contact during
      ablation. However, interactions between the ablation process, or its associated
      irrigation flow changes, with the CF sensing may translate into unexpected CF
      value fluctuations. We aimed to test for unintentional CF value variations during
      radiofrequency applications at a fixed applied force, with two commercially
      available catheters (TactiCathTM and SmartTouchTM), and to evaluate its
      theoretical clinical significance by correlating CF-derived automatic ablation
      algorithms (force-time integral and lesion index) and actual lesion size at two
      standard CF values. METHODS: Four series of 20 perpendicular epicardial ablations
      (20 W, 60 s, 17 ml/min) were performed on porcine left ventricle submerged in 37 
      degrees C saline. Catheters were mechanically fixed at a constant position and
      evaluated at 10 and 20 g. CF values were digitally analysed before each
      application changing irrigation rate (2-17-30 ml/min), and during ablation.
      Finally, lesions were quantified. RESULTS: Increasing irrigation before ablation
      led to a slight but significant CF decrease. During ablation, CF showed a
      reproducible pattern: fast initial decrease, subsequent increase until higher
      than-initial values and final plateau phase (CF variation up to 69% at 10 g). CF
      variability was significantly higher at 10 g and using TactiCathTM. There were no
      major differences in lesion size between catheters at the same initial CF. CF
      only correlated mildly to lesion measures, and automatic algorithms globally
      failed to predict lesion size. CONCLUSIONS: CF measured values spontaneously vary
      during ablation following a predictable pattern (initial decrease, subsequent
      increase and final plateau). This is especially remarkable applying lower CF.

PMID- 30109527
TI  - Analysis of spatial distribution of trace metals, PCB, and PAH and their
      potential impact on human health in Virginian Counties and independent cities,
      USA.
AB  - Increasing anthropogenic alteration has resulted in increased exposure to both
      point and nonpoint source pollution. These exposures are increasingly studied for
      their role in human diseases, including diseases with known genetic or lifestyle
      risk factors. This study analyzed associations between a variety of human
      diseases and trace metals, PCBs, and PAHs in soil, groundwater, sediment, and
      fish. Contaminant spatial data at the county level from Virginia were used in
      ArcGIS to identify these associations among socially vulnerable populations. The
      neurologic and psychiatric disorders and cognitive markers were associated with
      numerous metals in groundwater/soil and/or aquatic system contaminants. Cancer
      death rates, fetal deaths, and infant deaths were also related to multiple
      environmental exposures from both categories of exposure. In contrast, many of
      the chronic diseases which are primarily attributed to lifestyle showed little
      association with these exposures with the exception of COPD which did appear to
      be associated with multiple metal exposures. Asthma showed similar associations
      compared to COPD. Our data suggest that within the context of socially vulnerable
      populations, where disease burden is often highest, exposures to metals, PAHs,
      and PCBs may play a role in the development or exacerbation of several highly
      prevalent categories of disease. These environmental exposures likely act through
      a variety of pathways all generally leading to increased oxidative stress,
      inflammation, or interference with biological systems and a subsequent role in
      disease development.

PMID- 30109528
TI  - Fluoridation and county-level secondary bone cancer among cancer patients 18
      years or older in New York State.
AB  - The decision whether to fluoridate drinking water continues to be controversial
      in some communities. Dental and skeletal fluorosis in response to chronic
      fluoride overexposure are cited as reasons to avoid community water fluoridation
      in spite of evidence of the oral and skeletal health benefits fluoridation
      confers. Community fluoridation of ~ 1 mg/L fluoride has not been found to be
      associated with primary bone cancer but is associated with improved bone
      strength. No studies have examined fluoride exposure and secondary bone cancer, a
      common metastasis with significant morbidity. We hypothesize that fluoridation
      could diminish the likelihood of secondary bone cancer due to its role in bone
      fortification. We examined the association between community water fluoridation
      category and prevalence of secondary bone cancer from 2008 to 2010 among cancer
      patients of 18 years of age or older in counties in New York State. Relative to
      counties with less than 25% of the water supply fluoridated, we report no
      association between secondary bone cancer among cancer patients in counties with
      25-75% of the water supply fluoridated (beta = 0.02, p = 0.96) and among those in
      counties with > 75% fluoridated (beta = 0.02, p = 0.97). We found no evidence of
      an association between community water fluoridation category and secondary bone
      cancer from 2008 to 2010 at the county level in New York State.

PMID- 30109530
TI  - The optokinetic response is effective to assess objective visual acuity in
      patients with cataract and age-related macular degeneration.
AB  - PURPOSE: To estimate objective visual acuity in subjects suffering from cataract
      and age-related macular degeneration via the optokinetic response evoked by a non
      conventional induction method (oktotype); in addition, to compare such objective
      outcome with the subjective acuity based on the ETDRS charts. METHODS: Patients
      were presented with 13 sequences of symbols arranged horizontally to form a
      serial pattern, moving from left to right at a constant rate. In each sequence,
      the size of the stimuli was reduced progressively, while the operator checked for
      the disappearance of the optokinetic response via a small video camera mounted on
      the test lens frame. The minimum angular size of the serial pattern able to evoke
      the optokinetic response (MAER) was referred to as the objective visual acuity of
      the subject. RESULTS: Correlation between logMAER and logMAR was significant in
      the cataract and macular degeneration group ([Formula: see text] = 0.70, p <
      .0001; [Formula: see text] = 0.63, p < .0007). In the two samples, the
      correspondence between subjective and objective visual acuity (as, respectively,
      decimal units and arbitrary decimal units) was satisfactory (concordance
      correlation coefficient: cataract group = 0.91 and AMD group = 0.93). Test-retest
      reliability of the oktotype was good for the cataract group and moderate for the
      AMD sample (Kappa 0.81 and 0.59, respectively). CONCLUSION: The oktotype seems a
      promising tool to objectively assess visual acuity in noncooperating subjects
      with cataract or macular degeneration. Further research on other clinical
      conditions is needed to clarify the suitability of the procedure in the clinical
      setting.

PMID- 30109529
TI  - Corneal endothelial decompensation due to airbag injury.
AB  - PURPOSE: We report a case of localized endothelial decompensation due to airbag
      deployment during a motor vehicle accident. CASE REPORT: A middle-aged woman
      involved in a motor vehicle accident presented with diminution of vision in left
      eye. Initial ocular examination revealed corneal abrasion, localized central
      corneal edema and mild anterior chamber reaction. An anterior-segment ocular
      coherence tomography (AS-OCT) revealed focal paracentral corneal edema. Patient
      was managed with lubricating eye drops and antibiotic steroid combination.
      Significant endothelial cell loss compared to right eye was noted on specular
      examination. At one- month follow-up, visual acuity recovered to 6/6 but the
      pleomorphism and polymegathism persisted. CONCLUSION: Airbag-related localized
      corneal endothelial decompensation is a less known occurrence. This case
      emphasizes on the fact that serial monitoring of endothelial counts and
      conservative management can prove beneficial in such scenarios.

PMID- 30109532
TI  - Cultural Orientation and Psychosocial Adjustment Among Immigrant Adolescents in
      South Korea.
AB  - The present study primarily uses Berry's theoretical model to examine national
      identity, acculturation (to South Korea), ethnic identity, and enculturation (to
      country-of-origin), and how they are linked to immigrant adolescents' aggression
      and depression in South Korea. Data were collected from 120 immigrant youths
      (i.e., those born in South Korea and those born in their country-of-origin) in
      eight middle schools. Analyses include multivariate regression and cluster
      analyses. Findings indicate that South Korean identity (m = 48, F = 77.0, p <
      .001), acculturation to South Korean culture (m = 44.9, F = 52.3, p < .01), and
      mother's Korean proficiency (m = 3.6, F = 10.9, p < .001) were higher among Korea
      born adolescents. Enculturation (m = 35.5, F = 13.7, p < .001) and depression (m
      = 36.4, F = 15.3, p < .001) were higher among foreign-born adolescents.
      Aggression (r = - .26, p < .01) and depression (r = - .46, p < .01) were lower
      among native-born Korean adolescents. South Korean identity (B = - .27, p = .02)
      and acculturation (B = - .28, p = .01) were negatively associated with
      aggression. South Korean identity (B = - .22, p = .04), acculturation (B = - .21,
      p = .03), and ethnic identity (B = - .17, p = .02) were negatively associated
      with depression. Integration youth (M = 12.7) and assimilation youth (M = 11.5)
      reported lower aggression than marginalization youth (M = 15.8, F = 5.48, p <
      .01). Assimilation type had better outcomes than separation and marginalization
      types.

PMID- 30109533
TI  - Food Insecurity and the Double Burden of Malnutrition of Indigenous Refugee Epera
      Siapidara.
AB  - The goal of this paper is to assess food and nutritional security status of an
      indigenous population who migrated from Colombia to Ecuador. We collected data
      about the perception of food insecurity, anthropometric and food intake (n =
      104). An analysis multivariate (Generalized Linear Model) we used to know the
      adequacy to the Dietary Reference Intake (DRI). All the households were food
      insecure, stunting affected 45.1% of children and adolescents and the 60% were
      overweight or obese women. Significant differences were observed by gender for
      energy, lipid, carbohydrate, fiber, and iron (p < 0.001). No age group meets the
      DRI for fiber, calcium and potassium (except in children 24-59 months) and iron.
      There was a deficiency in vitamins A, D, folic acid and thiamine. The Epera
      Siapidara people in Ecuador experience acute food insecurity and a double burden
      of malnutrition, which may seriously affect their health and general progress.

PMID- 30109534
TI  - Mental Health Status and Service Assessment for Adult Syrian Refugees Resettled
      in Metropolitan Atlanta: A Cross-Sectional Survey.
AB  - Because little is known about the mental health status of Syrian refugees in the
      United States, we conducted a survey among a convenience sample of those
      resettled in Atlanta between March 2011 and 2017. Though home visits, we
      delivered a questionnaire including standardized instruments (HSCL25 and PTSD-8)
      to assess symptoms of anxiety, depression and Posttraumatic Stress Disorder. We
      found high rates of anxiety (60%), depression (44%) and Posttraumatic Stress
      Disorder (84%) symptoms; however, only 20% of participants had seen a mental
      health professional. Reported reasons for not seeking professional help were lack
      of transportation and access to information. Findings of this survey indicate the
      high burden of mental health symptoms and the need for services to the study
      population. A longitudinal study with a larger sample size would improve the
      understanding of mental health needs and resilience factors of Syrian refugees
      resettled in the US.

PMID- 30109531
TI  - Childhood diet and growth in boys in relation to timing of puberty and adult
      height: the Longitudinal Studies of Child Health and Development.
AB  - PURPOSE: To begin to explore the possible roles of childhood diet and growth in
      prostate cancer (PCa) development, we investigated these exposures in relation to
      two known/suspected PCa risk factors, earlier pubertal timing and greater
      attained height, in the Longitudinal Studies of Child Health and Development.
      METHODS: We used biannual/annual height, weight, and dietary history data to
      investigate childhood diet, body mass index (BMI), birth length, and childhood
      height in relation to PCa risk factors (age at peak height velocity (APHV),
      height at age 13, and adult height) for 64 Caucasian American boys. RESULTS: In
      adjusted models, childhood fat and animal protein intake was positively
      associated with height at age 13 and adult height (P < 0.05). A childhood diet
      high in fat and animal protein and low in vegetable protein was also associated
      with earlier APHV (P < 0.05), whereas no associations were observed for childhood
      energy intake or BMI. Birth length and childhood height were positively
      associated with height at age 13 and adult height, and childhood height was
      inversely associated with APHV (P < 0.05). CONCLUSION: Our findings suggest that
      both childhood diet and growth potential/growth contribute to earlier pubertal
      timing and taller attained height in males, supporting roles of these factors in
      PCa development.

PMID- 30109535
TI  - Transurethral thulium laser enucleation versus resection of the prostate for
      treating benign prostatic hyperplasia: a retrospective study.
AB  - This study aimed to compare the clinical outcomes between transurethral thulium
      laser enucleation of the prostate (ThuLEP) and transurethral thulium laser
      resection of the prostate (ThuLRP) for treating benign prostatic hyperplasia
      (BPH). From May 2014 to August 2015, 212 patients underwent ThuLRP and 188
      patients underwent ThuLEP. The ThuLEP group was further divided into two
      subgroups according to the ways the prostate was taken out. The perioperative
      parameters were recorded and analyzed. The international prostate symptom score
      (IPSS), quality-of-life (QoL) score, maximum flow rate (Qmax), and postvoid
      residual urine volume (PVR) in both groups were estimated and compared 3, 6, and
      12 months after surgery. No significant difference was observed between the
      groups in terms of irrigated time, irrigated volume, catheterization time, and
      hospital stay. However, the significantly lower hemoglobin drop was observed in
      the ThuLRP group compared with the ThuLEP group. The ThuLEP group with a
      morcellator required a shorter operation time for patients with large prostate
      volume (> 60 mL) compared with the ThuLRP and ThuLEP groups without a
      morcellator. During 12 months of follow-up, IPSS, Qmax, QoL, and PVR improved
      significantly without significant differences between the groups. No severe
      complications were reported; however, the occurrence of transient urge
      incontinence was higher after ThuLEP compared with ThuLRP, and the proportion of
      urinary tract infection after surgery was higher in ThuLRP than in ThuLEP. ThuLRP
      and ThuLEP are safe and efficient for treating patients with symptomatic BPH.
      ThuLRP offers advantages in terms of minimal blood loss.

PMID- 30109536
TI  - Effects of the extracorporeal shock wave therapy on the skin: an experimental
      study.
AB  - Extracorporeal shock wave therapy (ESWT) has been extensively studied for its
      multiple biological properties, and although it is widely applied in esthetical
      procedures, little is known about its effects on the epidermis and dermis. In
      this study, a histological and immunohistochemical study of the effects of ESWT
      was performed on rat skin. Forty-five female rats were treated with one or two
      sessions of ESWT and sacrificed on days 1, 7, 14, and 21 after treatment. The
      samples were histologically processed and then morphometric analyses were
      performed to assess the epidermis, dermis, and subcutaneous fat tissue thickness.
      Immunohistochemical reactions were also performed against the antibodies: basic
      fibroblastic growth factor (FGF2), its receptor (FGFR1), and alpha-smooth muscle
      actin. Slides were scanned and digitally assessed, to determine the microvessel
      density (MVD) and digital scoring of the immunohistochemical staining. The
      results showed that ESWT produced a significantly higher collagen content, MVD,
      and epidermis and dermis thickness than the control, non-treated group. Both in
      epidermis and dermis, FGF2 was overexpressed in the ESWT-treated groups, whereas
      FGFR1 was increased only in the group treated with two ESWT sessions at 21-days
      post-treatment. The ESWT-treated groups have also shown diminished thickness of
      subcutaneous fat tissue. In conclusion, ESWT induces neocollagenesis and
      neoangiogenesis, and upregulates the FGF2 expression, particularly in the groups
      treated with two sessions. Furthermore, it was demonstrated that overexpression
      of FGF2 on skins treated with ESWT seems to be a key role on its mechanism of
      action.

PMID- 30109537
TI  - Robotic Nipple-Sparing Mastectomy and Immediate Breast Reconstruction with Gel
      Implant: Technique, Preliminary Results and Patient-Reported Cosmetic Outcome.
AB  - BACKGROUND: Experience with application of a robotic surgery platform in the
      management of breast cancer is limited. The preliminary results of the robotic
      nipple-sparing mastectomy (R-NSM) and immediate breast reconstruction (IBR) with
      Gel implant procedure are reported. METHODS: The medical records of patients from
      a single institution who underwent an R-NSM and IBR with Gel implant procedure
      for breast cancer during the period March 2017 to February 2018 were assessed.
      Data on clinicopathologic characteristics, type of surgery, complications, and
      recurrence were analyzed to determine the effectiveness and oncologic safety of R
      NSM. Patient-reported cosmetic outcome results were obtained. RESULTS: A total of
      22 patients who received 23 R-NSM and IBR with Gel implant procedures were
      analyzed. The mean operation time for R-NSM was 118.8 +/- 50.6 min, and 74.5 +/-
      26.6 min for Gel implant reconstruction. Docking time quickly dropped from 20 to
      6-8 min, and the time needed to complete R-NSM was usually completed within 100
      min after accumulation of case experience. Mean blood loss was 37 +/- 38.2 mL,
      and the positive surgical margin rate was 0%. Three (13%) patients had transit
      nipple ischemia change, and no total nipple-areolar complex necrosis cases were
      observed. No local recurrence or mortality was found during a mean 6.9 +/- 3.5
      months of follow-up. All 22 patients were satisfied with the postoperative
      aesthetic outcome. CONCLUSION: From our preliminary experience, R-NSM and IBR
      with Gel implant is a safe procedure, with good cosmetic results, and could be a
      promising new technique for breast cancer patients indicated for mastectomy.

PMID- 30109538
TI  - Reconstruction in the Metastatic Breast Cancer Patient: Results from the National
      Cancer Database.
AB  - PURPOSE: Modern treatments are prolonging life for metastatic breast cancer
      patients. Reconstruction in these patients is controversial. The purpose of this
      study was to characterize de novo metastatic breast cancer patients who undergo
      mastectomy and reconstruction and to report complication and survival rates.
      METHODS: We queried the National Cancer Database for de novo metastatic breast
      cancer patients, who underwent systemic therapy and mastectomy with
      reconstruction (R) or without reconstruction (NR) between 2004 and 2013. Patient
      tumor characteristics, mortality, and readmissions were compared. Propensity
      score matched analysis was performed, and survival was calculated using the
      Kaplan-Meier method. RESULTS: A total of 8554 patients fulfilled study criteria
      (n = 980/11.5% R vs. n = 7574/88.5% NR). There was a significant increase in
      reconstruction rates by year: 5.2% in 2004, 14.3% in 2013 (p < 0.0001). Compared
      with the NR patients, R patients were younger (mean age 49 vs. 58 years, p <
      0.0001), more hormone receptor-positive (76.1% vs. 70.5%, p = 0.0004), had lower
      grade disease (p = 0.0082), and fewer sites of metastases (85.7% had 1
      metastasis; 14.3% had >= 2 R vs. 79% had 1; 21% had >= 2 NR, p = 0.0002). R
      patients received more hormonal and chemotherapy than NR but equally received
      radiation. Median overall survival of the total cohort was 45 months, and median
      overall survivals of R and NR groups by matched analysis were 56.7 and 55.3
      months respectively (p = 0.86). Thirty-day mortality (0.2%-R, 0.3%-NR, p = 0.56)
      and readmissions (5.9%-R, 5.8%-NR, p = 0.81) were similar; 90-day mortality also
      was similar (1.1%-R vs. 1.6%-NR, p = 0.796). CONCLUSIONS: There is an increasing
      trend to reconstruct metastatic breast cancer patients with low complication
      rates, without survival compromise. Impact on quality of life warrants further
      assessment.

PMID- 30109541
TI  - Letter to the editor.

PMID- 30109540
TI  - Correction to: Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts
      Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide
      Receptor Radionuclide Therapy.
AB  - The article "Pre-therapy Somatostatin Receptor-Based Heterogeneity Predicts
      Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide
      Receptor Radionuclide Therapy," was originally published electronically on the
      publisher's internet portal without open access.

PMID- 30109539
TI  - Females in the forefront: time-based intervention effects on impulsive choice and
      interval timing in female rats.
AB  - Impulsive choice has been implicated in substance abuse, gambling, obesity, and
      other maladaptive behaviors. Deficits in interval timing may increase impulsive
      choices, and therefore, could serve as an avenue through which suboptimal
      impulsive choices can be moderated. Temporal interventions have successfully
      attenuated impulsive choices in male rats, but the efficacy of a temporal
      intervention has yet to be assessed in female rats. As such, this experiment
      examined timing and choice behavior in female rats, and evaluated the ability of
      a temporal intervention to mitigate impulsive choice behavior. The temporal
      intervention administered in this study was successful in reducing impulsive
      choices compared to a control group. Results of a temporal bisection task
      indicated that the temporal intervention increased long responses at the shorter
      durations. Further, results from the peak trials within the choice task combined
      with the progressive interval task suggest that the intervention increased
      sensitivity to delay and enhanced timing confidence. Overall, these results
      indicate that a temporal intervention can be a successful avenue for reducing
      impulsive choice behavior in female rats, and could contribute to the development
      of behavioral interventions to prevent impulsive choice and maladaptive behaviors
      that can be applied to both sexes.

PMID- 30109542
TI  - Somatostatin analogue, Octreotide, improves restraint stress-induced liver injury
      by ameliorating oxidative stress, inflammatory response, and activation of
      hepatic stellate cells.
AB  - The aim of this study is to investigate the effect of somatostatin (SST)
      analogue, Octreotide, on some features of liver injury induced by immobilization
      stress (IS) in adult male albino rats. Eighteen adult male albino rats were
      randomly divided into three equal groups: control, IS, and Octreotide-treated
      stressed groups. Octreotide (40 MUg/kg body weight, subcutaneously) was
      administrated twice daily for 8 days during the exposure to IS. Octreotide was
      found to reduce the IS significantly and induce elevations in the plasma level of
      corticosterone, liver transaminases, and tumor necrosis factor alpha (TNF-alpha)
      as compared with IS group. Furthermore, Octreotide administration has
      significantly elevated the decline in the total antioxidant capacities (TAC) and
      lowered the elevated malondialdehyde (MDA) levels observed with IS in the hepatic
      tissue. Additionally, Octreotide treatment provided protection against the
      histopathological changes in the stressed liver in the form of significant
      reduction in the mean number of degenerated hepatocytes, the area % of collagen
      fibers, and glial fibrillary acid protein (GFAP) immunostaining with a
      significant increase in the mean number of normal hepatocytes. In conclusion,
      stressed rats showed disturbed liver functions and its oxidant-antioxidant status
      with highly expression hepatic stellate cells (HSCs), which were all improved by
      Octreotide administration, SST analogue.

PMID- 30109543
TI  - Prognostic significance of neutrophil/lymphocyte ratio (NLR) and correlation with
      PET-CT metabolic parameters in small cell lung cancer (SCLC).
AB  - PURPOSE: The aim of this study is to detect the prognostic significance of
      neutrophil/lymphocyte ratio (NLR) in SCLC and to evaluate the relation with 18F
      FDG PET-CT metabolic parameters (PET-CT MPs). METHODS: Demographic parameters,
      laboratory values including NLR and other clinical variables were analyzed in 112
      patients with small cell lung cancer (SCLC) and 54 of these patients had results
      of metabolic parameters detected with 18 FDG PET-CT [including SUVmax, SUVmean,
      metabolic tumor volume (MTV), whole body MTV (WBMTV), TLG (total lesion
      glycolysis), whole body TLG (WBTLG)] were evaluated for survival analyses.
      RESULTS: Mean and median overall survival (OS) and progression-free survival
      (PFS) were found to be significantly longer in cases with NLR < 4 compared with
      NLR > 4 in totally. Also stage, performance status, response to first-line
      therapy, LDH, and lymphocyte count were found to be prognostic for OS and PFS.
      MTV, WBMTV and WBTLG were found to be prognostic for both OS and PFS, while
      SUVmax found to be significant for OS. Patients with NLR >= 4, MTV >= 60.1, WBMTV
      >= 120 and WBTLG >= 1000 points had lower OS and PFS. A moderate positive
      correlation was found between NLR and SUVmean (r: 0.36), SUVmax (r: 0.34), TLG
      (r: 0.39), MTV (r: 0.51), WBMTV (r: 0.40), and WBTLG (r: 0.46). CONCLUSION: There
      is relationship between PET-CT metabolic parameters and NLR in SCLC. Highest
      correlation was found with NLR and MTV, WBMTV, and WBTLG, and evaluation of NLR
      together with these parameters predicts survival times and tumor biology more
      clearly in SCLC.

PMID- 30109544
TI  - Phase II feasibility study of preoperative concurrent chemoradiotherapy with
      cisplatin plus 5-fluorouracil and elective lymph node irradiation for clinical
      stage II/III esophageal squamous cell carcinoma.
AB  - BACKGROUND: Preoperative chemoradiotherapy (CRT) is a standard treatment for
      stage II/III esophageal cancer. Preoperative chemotherapy is also considered a
      standard treatment for stage II/III esophageal squamous cell carcinoma (ESCC) in
      patients who undergo radical lymph node dissection. We conducted a feasibility
      study of preoperative CRT with cisplatin plus 5-fluorouracil (CF) and elective
      lymph node irradiation followed by esophagectomy with radical lymph node
      dissection in patients with stage II/III ESCC. METHODS: Patients with clinical
      stage II/III, excluding T4, ESCC (International Union Against Cancer TNM
      classification system, 6th edition) were eligible. Chemotherapy comprised two
      courses of CF infusion repeated after 4-weeks. Radiation therapy was concurrently
      administered to the primary tumor, metastatic lymph nodes, and regional lymph
      nodes at a dose of 41.4 Gy. After the completion of CRT, transthoracic
      esophagectomy with 2-3 fields lymphadenectomy was performed. The primary endpoint
      was the completion rate of protocol treatment with R0 resection. RESULTS: Thirty
      one eligible patients were enrolled. During CRT, the most common grade 3 or 4
      toxicities were leukopenia (65%), neutropenia (65%), anemia (13%),
      thrombocytopenia (13%), febrile neutropenia (13%), anorexia (16%), esophagitis
      (16%) and hyponatremia (16%). Thirty patients (96.8%) underwent surgery. One
      patient received palliative chemotherapy because of appearance of lung metastasis
      during CRT. The completion rate of protocol treatment was 93.5% (29/31). There
      was one treatment-related death after surgery. Pathological complete response was
      achieved in 42% (13/30). CONCLUSION: Preoperative CRT with CF and elective lymph
      node irradiation showed an acceptable toxicity and promising activity especially
      in ESCC.

PMID- 30109545
TI  - A Survival Guide to Low-Resource Peer-Reviewed Creative Scholarship for Aspiring
      Clinician-Educators.

PMID- 30109546
TI  - Biodiesel synthesis from Chlorella vulgaris under effect of nitrogen limitation,
      intensity and quality light: estimation on the based fatty acids profiles.
AB  - Cultures under nitrogen limitation for Chlorella vulgaris were kept under
      different light quality (white, blue, yellow and violet) at 70 and 140 uE m-2 s
      1; to evaluate the effect on fatty acids profiles and biodiesel quality. The
      results showed a maximum biomass and cell density at 140 uE m-2 s-1 of: white
      light (0.69 g L-1 and 6.5 * 106 cells mL-1, respectively) and blue light (0.65 g
      L-1 and 8.0 * 106 cells mL-1, respectively); compared to violet and yellow light.
      The chlorophyll concentration (ug mg-1 biomass dry weight) at 70 uE m-2 s-1 were
      in the order of light: white (25.61) > violet (17.10) > yellow (11.68) > blue
      (11.40) and, at 140 uE m-2 s-1 were: violet (23.64) > white (10.20) > yellow
      (9.66) > blue (7.99), suggesting the violet light stimulates the increase of
      chlorophyll a at higher intensity. The maximum lipid content (% w/w) were present
      under blue light (43.11), yellow (70.92) and violet (83.87) at 140 uE m-2 s-1.
      The different wavelengths did not have a negative effect on the quality of the
      biodiesel, however; violet light presented greater productivity and the
      indicators such as CFPP were related to the oxidative stability value and low
      PUFA content, leading biodiesel to good oxidative stability.

PMID- 30109549
TI  - A Comparative Study of Iodized Salt Programs: Shanghai and Switzerland.

PMID- 30109547
TI  - Response of Lablab purpureus L. to high temperature stress and role of exogenous
      protectants in mitigating high temperature induced oxidative damages.
AB  - Present study was conducted to explore the role of exogenous salicylic acid (SA),
      sodium nitroprusside (SNP), abscisic acid (ABA) and proline (PRO) in mitigating
      high-temperature (HT) induced oxidative stress in different Lablab purpureus L.
      cultivars. The attempt was made to examine whether these phytohormones, when
      applied exogenously, were able to regulate plant morpho-physiological behavior by
      modulating genes and proteins involved in antioxidant defense system. The HT
      stress induced membrane damage, degraded chlorophyll, generated redox metabolites
      and significantly reduced growth and biomass in all the cultivars. Among all the
      four treatments, foliar application of SA and SNP were most effective in the
      regulation of growth and physiological processes of the cultivars compared to ABA
      and PRO applications. Thus, signifying the protective role of SA and SNP in
      mitigation of HT induced oxidative stress and conferring HT stress tolerance in
      the cultivars. Gene expression and leaf proteome analysis revealed that these
      phytohormones were also involved in regulation of defense related gene
      expression, stress inducible proteins and de novo synthesis of specific proteins
      under HT stress. The experimental findings depict that foliar applications of SA
      and SNP enhances HT stress tolerance in lablab cultivars by modulating
      antioxidant defense system and by regulating bio-physical growth more effectively
      as compared to ABA and PRO application.

PMID- 30109550
TI  - Chronic Oral Arsenic Exposure and Its Correlation with Serum S100B Concentration.
AB  - Arsenic is one of the most important environmental pollutants especially in
      drinking water. The S100B protein is presented as a sensitive biomarker for
      assessment of the blood-brain barrier integrity previously. The objective of this
      study was to determine the impact of chronic arsenic exposure in drinking water
      and serum S100B correlation. Fifty-four male BALB/c mice were randomly divided
      into three groups. Group I and II subjects were treated with arsenic trioxide (1
      ppm and 10 ppm, respectively), while the rest received normal drinking water.
      Arsenic concentration in serum and brain was measured by an atomic absorption
      spectrometer (Varian model 220-Z) conjugated with a graphite furnace atomizer
      (GTA-110). Also, a serum S100B protein concentration was determined using
      commercial ELISA kit during different times of exposure. It was observed that
      body weight gain was significantly lower from the 10th week onwards in arsenic
      treated subjects. However, it did not induce any visible clinical signs of
      toxicity. Measured arsenic level in serum and brain was higher in espoused groups
      as compared to the control subjects (p < 0.001 and p < 0.0001, respectively). In
      addition, serum S100B content was increased over a period of 3 months and had
      significant differences as compared to the control and 1-ppm group especially
      after 3 months of exposure in the 10-ppm group (p < 0.0001). In conclusion, it
      could be inferred that long-term arsenic exposure via drinking water leads to
      brain arsenic accumulation with serum S100B elevated concentration as a probable
      BBB disruption consequence.

PMID- 30109548
TI  - Rapid, simple and potentially universal method for DNA extraction from Opuntia
      spp. fresh cladode tissues suitable for PCR amplification.
AB  - In Opuntia spp., the cladode tissues contain many polysaccharides and secondary
      metabolites that interfere with obtaining high-quality deoxyribonucleic acid
      (DNA), using currently available methods. To circumvent this problem, three
      commercial kits, three modified versions of the conventional
      cetyltrimethylammonium bromide method (CTAB) method and one combined method were
      tested in Opuntia ficus-indica, O. robusta, O. dillenii and O. elata species. We
      obtained a rapid and simple protocol that allows the extraction of DNA from all
      the tested species with good DNA yield and purity, namely, the combined method.
      With this method (DNeasy(r) Plant Mini Kit combined with the CTAB method), DNA
      yields from 13.2 +/- 7.8 to 15.9 +/- 11.3 ug g-1 of fresh tissue were obtained in
      the four Opuntia species. The purity, evaluated by the ratio A260/A280 ratio,
      ranged from 1.67 +/- 0.12 to 2.01 +/- 0.25, revealing low levels of problematic
      metabolites. The extracted DNA quality was confirmed by amplifying a set of
      nuclear microsatellites obtained for the genus. Reliable reproducible bands and
      electropherogram profiles were obtained. The combined method has potential to be
      universal for good-quality DNA extraction in cacti, particularly in the Opuntia
      genus and other difficult-to-extract species.

PMID- 30109551
TI  - Long-Term Effects of Unmodified 50 nm ZnO in Mice.
AB  - Nanometer zinc oxide (nano-ZnO) is widely used in many kinds of fields. However,
      information about the toxicity and toxic mechanism of nano-ZnO is limited. The
      aims of this study were to investigate the long-term toxic effects of unmodified
      50 nm ZnO administered by gavage in mice. After 90 days, hematological
      parameters, hepatic and renal functions, and oxidative and anti-oxidative status
      were measured. Pathological damages in livers, kidneys, and other tissues were
      also examined by hematoxylin and eosin (H&E) staining. The results showed that
      oral nano-ZnO exposure induced anemia and damages to liver and kidney, influenced
      the antioxidant system, and impacted functions of liver and kidney in mice after
      a 90-day exposure. The main cause for oxidative stress in vivo induced by nano
      ZnO might be hydroxyl free radical. The lowest observed adverse effect level
      (LOAEL) was 40 mg/kg.bw, and the livers, kidneys, lungs, pancreas, and
      gastrointestinal tracts are the target organs.

PMID- 30109552
TI  - Correction to: Ultrasound-guided transversus abdominis plane block (US-TAPb) for
      robot-assisted radical prostatectomy: a novel '4-point' technique-results of a
      prospective, randomized study.
AB  - The author would like to correct the errors in the publication of the original
      article due to multiple small errors in scientific content of article due to
      author oversight. Errors do not change or invalidate conclusion of article.

PMID- 30109554
TI  - Phase I clinical trial of percutaneous cryoablation for osteoid osteoma.
AB  - PURPOSE: This prospective phase I trial was conducted to evaluate the safety of
      percutaneous cryoablation for osteoid osteoma (OO). MATERIALS AND METHODS: Nine
      patients with OO (mean tumor size: 5.9 mm; tibia, n = 5; femur, n = 2; lumbar
      spine, n = 2) were enrolled and treated with percutaneous cryoablation. The
      primary endpoint was the evaluation of the treatment safety as determined using
      step-by-step registration. The secondary endpoints were the incidence and grade
      of adverse events by CTCAE version 4.0, and the short-term efficacy of this
      treatment. Based on a decrease in the numerical rating scale (NRS) score,
      efficacy was classified as significantly effective (SE >= 5 or reached 0-2),
      moderately effective (ME 2-4), or not effective (NE < 2 or increase). RESULTS:
      Cryoablation procedures were completed in all patients. Major adverse events (>=
      grade 3) related to the procedure were not observed. Minor adverse events (<=
      grade2) were observed in 22-67%. The mean NRS score was 7 before treatment, 0.6
      at 4-week, 0.1 at 6-month, and 0 at 1-year post-treatment. All procedures were
      classified as SE. CONCLUSION: Percutaneous cryoablation is a safe treatment for
      OO. Future phase II trials with large patient cohorts are warranted.

PMID- 30109553
TI  - Multicenter investigation of the incidence of inferior vena cava filter fracture.
AB  - PURPOSE: Inferior vena cava filter fracture (FF) may cause life-threatening
      complications, including cardiac tamponade, although the actual prevalence
      remains unclear. Therefore, we investigated the incidence of FF. MATERIALS AND
      METHODS: Data on fracture incidence with filter brands, filter positions
      [suprarenal (SR) vs. infrarenal (IR)], and follow-up durations were collected
      from the databases of eight hospitals. RESULTS: Of 532 patients, Gunther Tulip
      (GT), Trap/OptEase (TE/OE), ALN and VenaTech (VT) were implanted in 345, 147, 38
      and 2 patients, respectively. Of these, filter retrieval was attempted in 110
      (21.7%) patients and was successful in 106 (96.4%). Of the remaining 426
      patients, FFs were observed in two (0.7%) of 270 GT filters and 19 (14.1%) of 135
      TE/OE filters. Fragment embolization occurred in one patient with a GT filter
      (50.0%) and three with a TE/OE filter (15.8%) with a total follow-up interval of
      718.0 +/- 1019.4 days. FF occurred more frequently in TE/OE than in GT filters (p
      < 0.001). Kaplan-Meier estimates showed significantly higher fracture-free rates
      for GT than TE/OE (p < 0.001) and IR-TE/OE than SR-TE/OE (p < 0.05). CONCLUSIONS:
      TE/OE filters are not suitable for permanent implantation due to the relatively
      early and high fracture rates.

PMID- 30109555
TI  - Non-calcifying Langerhans Cell-Rich Variant of Calcifying Epithelial Odontogenic
      Tumor: A Distinct Entity with Predilection for Anterior Maxilla.
AB  - Calcifying epithelial odontogenic tumor (CEOT) is an uncommon locally invasive
      epithelial odontogenic tumor of the jaws associated with amyloid production.
      Intraosseous presentations are most common and they frequently occur in the
      posterior mandible. A non-calcifying Langerhans cell-rich variant of CEOT (NCLC
      CEOT) has been described with predilection for the anterior maxilla.
      Interestingly, all reported cases of NCLC CEOT have occurred in Asian population.
      We present a case of a 43-year old Caucasian female with a large radiolucent
      lesion involving the left anterior maxilla with histologic features of NCLC CEOT.
      This is the first reported case of this rare variant of CEOT in a Caucasian
      individual.

PMID- 30109556
TI  - NMDA Receptor Dependent Long-term Potentiation in Chronic Pain.
AB  - Since the discovery of NMDA receptor (NMDAR) dependent long-term potentiation
      (LTP) in the hippocampus, many studies have demonstrated that NMDAR dependent LTP
      exists throughout central synapses, including those involved in sensory
      transmission and perception. NMDAR LTP has been reported in spinal cord dorsal
      horn synapses, anterior cingulate cortex and insular cortex. Behavioral, genetic
      and pharmacological studies show that inhibiting or reducing NMDAR LTP produced
      analgesic effects in animal models of chronic pain. Investigation of signalling
      mechanisms for NMDAR LTP may provide novel targets for future treatment of
      chronic pain.

PMID- 30109557
TI  - Synthesis of aminouracil-tethered tri-substituted methanes in water by iodine
      catalyzed multicomponent reactions.
AB  - An efficient, mild and environmentally benign protocol has been developed for the
      synthesis of aminouracil-tethered tri-substituted methane derivatives. The three
      component reaction of 2-hydroxy-1,4-naphthaquinone, 6-amino-1,3-dimethyluracil
      and aldehydes in the presence of molecular iodine as catalyst under reflux
      conditions resulted in aminouracil-tethered tri-substituted methane derivatives 4
      in aqueous medium. Similarly, the four-component reaction of 2-hydroxy-1,4
      naphthaquinone, o-phenylenediamine, aldehydes and aminouracil derivatives
      resulted in aminouracil-tethered tri-substituted methane derivatives 6 under the
      same reaction conditions. The notable features of this protocol are simple
      experimental procedure, cheap catalyst, readily available starting materials,
      moderate-to-good yields of the products having biologically active important
      moieties such as aminouracil, hydroxy-naphthaquinone/benzophenazine.

PMID- 30109558
TI  - The association between autosomal dominant polycystic kidney disease and cancer.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is considered as a tumor
      like disease because there are many biological similarities between ADPKD and
      cancer. However, the commonalities between them are provocative, particularly
      under the conditions of recent clinical studies. In this paper, we review
      clinical studies about the association between cancer and ADPKD, and compare the
      biological characteristics between them, with focusing on cell proliferation,
      differentiation, migration, apoptosis, and polarity. With detailed literature
      reviewing, we believe that ADPKD patients have a higher risk of tumorigenesis and
      thus highly recommend being aware of tumorigenesis during follow-up in patients
      with ADPKD.

PMID- 30109560
TI  - The Role of kguT Gene in 2-Ketogluconate-Producing Pseudomonas plecoglossicida
      JUIM01.
AB  - Pseudomonas are ubiquitous bacteria that can live under a wide range of
      environmental conditions; some species are successfully used in the fermentation
      industry. Pseudomonas plecoglossicida JUIM01 strain is an important industrial 2
      ketogluconate (2KGA) producer. In Pseudomonas, kguT gene encodes a putative 2KGA
      transporter KguT, and there is no detailed research on the role of KguT. In this
      work, the role of KguT in P. plecoglossicida JUIM01 was investigated. The results
      showed that the KguT of P. plecoglossicida JUIM01 plays an essential role in the
      transport of 2KGA into cells; inactivation of KguT could prevent the assimilation
      of 2KGA as carbon source by the cells and had no negative effect on 2KGA
      biosynthesis. Under fermentation conditions, the kguT deletion strain had the
      same capability of 2KGA production with P. plecoglossicida JUIM01 and avoided the
      assimilation of the product 2KGA by cells after the depletion of glucose. These
      results can provide references for Pseudomonas study and fermentation production
      of 2KGA.

PMID- 30109559
TI  - Association between MCP-1 2518 A>G gene polymorphism and chronic kidney disease.
AB  - Monocyte chemoattractant protein-1 (MCP-1) is involved in the pathogenesis of
      chronic kidney diseases (CKD). MCP-1 2518 A>G gene polymorphism is associated
      with MCP-1 status. We performed a meta-analysis to assess the association between
      MCP-1 2518 A>G gene polymorphism and CKD risk. The eligible studies regarding the
      relationship between MCP-1 2518 A>G gene polymorphism and CKD risk were searched
      through electronic databases. The pooled odds ratios (ORs) and its 95% confidence
      intervals (CIs) were calculated by using a fixed-effects model, or in the
      presence of heterogeneity, a random-effects model. A total of 2415 cases and 2011
      controls were recruited in our investigation. A allele/GG genotype was not
      associated with CKD risk in overall populations, Asians, Caucasians, and
      Africans. AA/AG genotype was not associated with the risk of CKD in overall
      populations, Asians, Caucasians, and Africans. AA genotype was associated with a
      lower risk of CKD in Caucasians (OR 0.816, 95% CI 0.703-0.947). AG genotype was
      associated with a higher risk of CKD in Caucasians (OR 1.230, 95% CI 1.042
      1.452). There was no marked publication bias. In conclusion, AA genotype may be a
      protective factor against CKD susceptibility in Caucasians. AG genotype may be a
      risk factor for CKD risk in Caucasians. However, more studies are needed in the
      future.

PMID- 30109561
TI  - A Comparison Between Full-COLD PCR/HRM and PCR Sequencing for Detection of
      Mutations in Exon 9 of PIK3CA in Breast Cancer Patients.
AB  - One of the most common somatic mutations in breast cancer is found in PIK3CA with
      a prevalence rate of 18-45%. Different variants of this gene are considered as
      resistance markers for treatment with HER2-targeted medicines. Conventional
      molecular methods such as Sanger sequencing are not able to detect mutations with
      low abundance in a mixture of wild-type DNA, especially in the early stages of
      cancer development. In this study, two methods of co-amplification at lower
      denaturation temperature PCR (COLD-PCR) and high-resolution melting (HRM) were
      combined for detection of mutations in exon 9 of PIK3CA; DNA, therefore, was
      extracted from MCF-7 and BT-474 as mutant and wild-type cell lines respectively.
      Thereafter, serial dilutions of extracted DNA were used to determine sensitivity
      of full-COLD PCR/HRM in comparison with conventional PCR sequencing as the gold
      standard method. Cell line experiments resulted in almost 30 fold increase in
      sensitivity by use of full-COLD PCR/HRM. In addition, 40 patients with primary
      breast cancer were investigated with the mentioned methods. As a result of this
      part of study, four mutations were detected by conventional PCR sequencing
      including E542K and E545K mutations in three and one samples respectively.
      Whereas, full-COLD PCR/HRM was able to detect one E542K mutation more than gold
      standard method which caused the percentage of sensitivity to get improved by
      2.5% (10 to 12.5%). Our results clearly demonstrated that full-COLD PCR/HRM could
      detect lower levels of mutations in wild-type background as a sensitive method
      with simple and cost-effective procedure; therefore, it can prospectively be used
      in screening of patients with early-stage breast cancers.

PMID- 30109565
TI  - A case of fatal osteolytic hypercalcemia complicated with IgG4-related ophthalmic
      disease leading to renal failure.
AB  - A 40-year-old male was hospitalized with renal impairment and severe
      hypercalcemia. His concentration of serum IgG4 was high, but serum whole PTH, 1
      25(OH)2 vitamin D3 and PTHrP were not elevated. Computed tomography showed
      swelling of the bilateral lacrimal glands and systemic lymphadenopathy. The
      histological findings of lacrimal gland biopsy fulfilled the diagnostic criteria
      of IgG4-related ophthalmic disease (IgG4ROD). Bone scintigraphy showed increased
      ectopic uptake in the stomach, heart, lungs, and kidneys. He died on day 16 of
      admission, although the therapies for hypercalcemia were continued. Autopsy
      results showed an increase of osteoclasts in the bone marrow and metastatic
      calcification in multiple organs, and excluded from the differential diagnosis
      other disorders which present lymph-node swelling and hypercalcemia such as
      cancer, lymphoma, Castleman's disease, and sarcoidosis. He was given a diagnosis
      of IgG4ROD with osteolytic hypercalcemia.

PMID- 30109564
TI  - Identification of pathways and genes associated with cerebral palsy.
AB  - Cerebral palsy (CP) is a non-progressive neurological disease, of which
      susceptibility is linked to genetic and environmental risk factors. More and more
      studies have shown that CP might be caused by multiple genetic factors, similar
      to other neurodevelopmental disorders. Due to the high genetic heterogeneity of
      CP, we focused on investigating related molecular pathways. Ten children with CP
      were collected for whole-exome sequencing by next-generation sequencing (NGS)
      technology. Customized processes were used to identify potential pathogenic
      pathways and variants. Three pathways (axon guidance, transmission across
      chemical synapses, protein-protein interactions at synapses) with twenty-three
      genes were identified to be highly correlated with CP. This study showed that the
      three pathways associated with CP might be the molecular mechanism of
      pathogenesis. These findings could provide useful clues for developing pathway
      based pharmacotherapies. Further studies are required to confirm potential roles
      for these pathways in the pathogenesis of CP.

PMID- 30109566
TI  - Letter to the editor: medical physics workforce modelling: do we need what we
      want?

PMID- 30109567
TI  - Prevalence of wormian bones in dried adult human skulls: an osteo-morphometric
      study in Nepal.
AB  - The purpose of this study was to determine the incidence of wormian bones (WBs)
      in different head shapes of Nepalese skulls along with their distribution at
      various sites. This study was conducted on 70 Nepalese skulls obtained from the
      Department of Anatomy, Nepal Medical College, and the Institute of Medicine from
      September 2017 to January 2018. The skulls were examined for the presence and
      topographic distribution of WBs. The occurrence of WBs at various sites was
      correlated among different head shapes. The incidence of skulls showing WBs was
      88.57%. The WBs were observed at the lambdoid (61.43%), parietomastoid (41.43%),
      occipitomastoid (27.14%), pterion (25.71%), asterion (24.29%), lambda (11.43%),
      sagittal (7.14%) and coronal sutures (4.28%). The dominant head type was
      dolichocephalic (44.29%) and the least dominant was brachycephalic (10%). The
      maximum number of WBs was shown on brachycephalic (mean 8.86 +/- 7.13) then
      hyperdolichocephalic (mean 8.33 +/- 9.15), mesaticephalic (mean 5.10 +/- 4.45)
      and dolichocephalic heads (mean 4.16 +/- 5.30). Brachycephalic heads frequently
      exhibited WBs at the pterion (57.14%) and at different sutures: lambdoid
      (71.42%), parietomastoid (57.14%), sagittal (28.57%) and squamous (14.28%).
      Hyperdolichocephalic heads displayed more lambda (33.33%) and coronal (8.33%)
      WBs. Similarly, dolichocephalic and mesaticephalic heads showed WBs at the
      occipitomastoid (35.48%) and asterion (30%), respectively. Inca bones were only
      identified in three dolichocephalic skulls. Neurosurgeons, radiologists and
      orthopedists should be careful when doing clinical and surgical procedures on
      different head shapes of the Nepalese population.

PMID- 30109562
TI  - Molecular imaging reporting and data systems (MI-RADS): a generalizable framework
      for targeted radiotracers with theranostic implications.
AB  - Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)
      targeted positron emission tomography (PET)-based imaging agents for prostate
      carcinoma and neuroendocrine tumors, respectively, are seeing rapidly expanding
      use. In addition to diagnostic applications, both classes of radiotracers can be
      used to triage patients for theranostic endoradiotherapy. While interpreting PSMA
      or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware
      of certain pitfalls. Adding to the complexity of the interpretation of those
      imaging agents, both normal biodistribution, and also false-positive and 
      negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein
      summarized under the umbrella term molecular imaging reporting and data systems
      (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging
      are described (PSMA- and SSTR-RADS). Notably, PSMA- and SSTR-RADS are structured
      in a reciprocal fashion, i.e., if the reader is familiar with one system, the
      other system can readily be applied, as well. In the present review, we will
      discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly
      introduce PSMA- and SSTR-RADS, and define a potential future role of the umbrella
      framework MI-RADS compared to other classification systems.

PMID- 30109568
TI  - Chronic Hyperglycaemia Induced Alterations of Hepatic Stellate Cells Differ from
      the Effect of TGFB1, and Point toward Metabolic Stress.
AB  - The deleterious effect of hyperglycemia on the biology of the liver is supported
      by clinical evidence. It can promote the development of fatty liver, liver
      fibrosis, even liver cancer as complication of diabetes mellitus. As liver
      fibrosis is the consequence of hepatic stellate cell (HSC) activation, the
      questions were addressed whether alterations induced by high glucose
      concentration are directly related to TGFB1 effect, or other mechanisms are
      activated. In order to obtain information on the response of HSC for high
      glucose, LX-2 cells (an immortalized human HSC cell lineage) were cultured in
      15.3 mM glucose containing medium for 21 days. The effect of glucose was compared
      to that of TGFB1. Our data revealed that chronic exposure of high glucose
      concentration initiated profound alteration of LX-2 cells and the effect is
      different from those observed upon interaction with TGFB1. Whereas TGFB1 induced
      the production of extracellular matrix proteins, high glucose exposure resulted
      in decreased MMP2 activity, retardation of type I collagen in the endoplasmic
      reticulum, with decreased pS6 expression, pointing to development of endoplasmic
      stress and sequestration of p21CIP1/WAF1 in the cytoplasm which can promote the
      proliferation of LX2 cells.

PMID- 30109569
TI  - A highly efficient electrophoretic method for discrimination between two
      Neoscytalidium species using a specific fungal internal transcribed spacer (ITS)
      fragment.
AB  - Neoscytalidium (or N.) dimidiatum and N. novaehollandiae are two aggressive plant
      pathogenic species that affect several agricultural crops. Early detection and
      identification of these fungi are of critical importance to bring about the
      effective minimization to the threat they pose to the infected plants. Herein,
      two species of Neoscytalidium were rapidly discriminated by utilizing the rRNA
      internal transcribed (ITS4-5.8S-ITS5) PCR primers. A total of 100 isolates of
      Neoscytalidium species, which were isolated from Iraqi canker-infected fig trees,
      were included in this study. Two discrete electrophoretic PCR bands were observed
      in Neoscytalidium isolates-A-variants were about 546 bp, while B-variants were
      about 993 bp in length. The comprehensive phylogenetic analysis of both DNA
      variants revealed that A-variants resided between N. novaehollandiae and N.
      hyalinum, while B-variants were closely related to N. dimidiatum. Furthermore,
      the highly specific re-constructed tree of both electrophoretic variants
      demonstrated that B-variants share a high similarity with N. novaehollandiae.
      Additionally, the secondary structures for both variants were predicted
      computationally to reveal the structural patterns that each variant follows. In
      conclusion, a small rRNA locus comprising 22 nucleotides that differs in the two
      variants is potentially responsible for this species-specific classification. The
      main divergence in the amplified loci led to the classification of these fungal
      variants into two main species, namely N. dimidiatum and N. novaehollandiae,
      demonstrating that the amplification by ITS4-ITS5 rRNA fragment is a beneficial
      strategy that can be employed for the assessment of Neoscytalidium diversity in
      the natural ecosystems.

PMID- 30109563
TI  - Transcriptional regulation of osmotic stress tolerance in wheat (Triticum
      aestivum L.).
AB  - KEY MESSAGE: The current review provides an updated, new insights into the
      regulation of transcription mediated underlying mechanisms of wheat plants to
      osmotic stress perturbations. Osmotic stress tolerance mechanisms being complex
      are governed by multiple factors at physiological, biochemical and at the
      molecular level, hence approaches like "OMICS" that can underpin mechanisms
      behind osmotic tolerance in wheat is of paramount importance. The transcription
      factors (TFs) are a class of molecular proteins, which are involved in
      regulation, modulation and orchestrating the responses of plants to a variety of
      environmental stresses. Recent reports have provided novel insights on the role
      of TFs in osmotic stress tolerance via direct molecular links. However, our
      knowledge on the regulatory role TFs during osmotic stress tolerance in wheat
      remains limited. The present review in its first part sheds light on the
      importance of studying the role of osmotic stress tolerance in wheat plants and
      second aims to decipher molecular mechanisms of TFs belonging to several classes,
      including DREB, NAC, MYB, WRKY and bHLH, which have been reported to engage in
      osmotic stress mediated gene expression in wheat and third part covers the
      systems biology approaches to understand the transcriptional regulation of
      osmotic stress and the role of long non-coding RNAs in response to osmotic stress
      with special emphasis on wheat. The current concept may lead to an understanding
      in molecular regulation and signalling interaction of TFs under osmotic stress to
      clarify challenges and problems for devising potential strategies to improve
      complex regulatory events involved in plant tolerance to osmotic stress adaptive
      pathways in wheat.

PMID- 30109570
TI  - A resected case of gallbladder metastasis with symptoms of acute cholecystitis in
      multiple metastatic ductal carcinoma of the breast.
AB  - Gallbladder metastasis from breast cancer, especially from ductal carcinoma, is
      rare. Herein, we report a rare case of gallbladder metastasis from ductal
      carcinoma of the breast that was diagnosed after laparoscopic cholecystectomy
      (LC) for acute cholecystitis. A 78-year-old woman presented with right upper
      abdominal tenderness and positive Murphy's sign during chemotherapy for advanced
      multiple metastases of the breast cancer. Abdominal ultrasonography and computed
      tomography showed a slightly thickened gallbladder wall and two calculi. After a
      diagnosis of acute calculous cholecystitis was established, LC was performed.
      Pathological examination revealed poorly differentiated adenocarcinoma
      infiltrating the submucosal and subserosal layer over the entire gallbladder, and
      a lymph node metastasis in the gallbladder neck. Immunohistochemical examination
      revealed that the tumor cells tested positive for estrogen receptor and negative
      for progesterone receptor, which was consistent with primary breast cancer. The
      patient was uneventfully discharged without abdominal pain 7 days later. Although
      she subsequently underwent several chemotherapies, she died 16 months later. In
      conclusion, gallbladder metastasis should be considered in patients with multiple
      metastatic breast cancer who present with signs or symptoms of cholecystitis.
      Moreover, LC should be considered to relieve the symptoms of cholecystitis for
      improved prognosis, even in a patient with multiple metastases.

PMID- 30109571
TI  - A case of early colorectal cancer with rectal varices treated with endoscopic
      variceal ligation.
AB  - Rectal varices are ectopic varices that occur in patients with portal
      hypertension and cause abrupt gastrointestinal bleeding. Endoscopic variceal
      ligation is a minimally invasive treatment used for patients with bleeding from
      rectal varices. Endoscopic treatment of colorectal tumors accompanied by rectal
      varices has been rarely reported. It is very important to control bleeding during
      treatment. The patient was a 76-year-old man who had a chief complaint of bloody
      stools. A flat-elevated-type neoplastic lesion measuring about 20 mm was found
      above the rectal varices. After performing endoscopic variceal ligation for
      rectal varices around the lesion, the lesion was resected en bloc by endoscopic
      submucosal dissection. Bleeding was controlled during the procedure; the patient
      was discharged 7 days after the endoscopic treatment, and there was no
      postoperative bleeding. Colonoscopy performed 90 days after the procedure showed
      scar formation in the wound area and no remnant lesion. The implementation of
      preoperative endoscopic variceal ligation enabled us to control bleeding during
      endoscopic treatment in a case of early colorectal cancer accompanied by rectal
      varices.

PMID- 30109573
TI  - Experience-guided attention: Uniform and implicit.
AB  - Frequently finding a visual search target in one region of space induces a
      spatial attentional bias toward that region. Past studies on this effect
      typically tested fewer than 20 participants. The small sample prevents an
      investigation of two properties of learning: visual field uniformity and role of
      explicit awareness. Pooling data from multiple studies, here we examined location
      probability learning from ~120,000 visual search trials across 420 participants.
      Participants performed a serial search task. Unbeknownst to them, the target was
      disproportionately likely to appear in one visual quadrant. Location probability
      learning (LPL) was measured as the difference in reaction time to targets in the
      high-probability "rich" quadrant and the low-probability "sparse" quadrants.
      Results showed a lack of visual field effect. LPL was equivalent for "rich"
      quadrant in the upper left, upper right, lower left, and lower right. Learning
      did not induce a hotspot diagonal to the "rich" quadrant. To the contrary, RT was
      the longest in the diagonal quadrant. Recognition rate of the "rich" quadrant was
      above chance. However, recognition accuracy was unrelated to the size of LPL.
      Implicit learning induces visual-field-independent changes in spatial attention.

PMID- 30109572
TI  - Automated prediction of dosimetric eligibility of patients with prostate cancer
      undergoing intensity-modulated radiation therapy using a convolutional neural
      network.
AB  - The quality of radiotherapy has greatly improved due to the high precision
      achieved by intensity-modulated radiation therapy (IMRT). Studies have been
      conducted to increase the quality of planning and reduce the costs associated
      with planning through automated planning method; however, few studies have used
      the deep learning method for optimization of planning. The purpose of this study
      was to propose an automated method based on a convolutional neural network (CNN)
      for predicting the dosimetric eligibility of patients with prostate cancer
      undergoing IMRT. Sixty patients with prostate cancer who underwent IMRT were
      included in the study. Treatment strategy involved division of the patients into
      two groups, namely, meeting all dose constraints and not meeting all dose
      constraints, by experienced medical physicists. We used AlexNet (i.e., one of
      common CNN architectures) for CNN-based methods to predict the two groups. An
      AlexNet CNN pre-trained on ImageNet was fine-tuned. Two dataset formats were used
      as input data: planning computed tomography (CT) images and structure labels.
      Five-fold cross-validation was used, and performance metrics included
      sensitivity, specificity, and prediction accuracy. Class activation mapping was
      used to visualize the internal representation learned by the CNN. Prediction
      accuracies of the model with the planning CT image dataset and that with the
      structure label dataset were 56.7 +/- 9.7% and 70.0 +/- 11.3%, respectively.
      Moreover, the model with structure labels focused on areas associated with dose
      constraints. These results revealed the potential applicability of deep learning
      to the treatment planning of patients with prostate cancer undergoing IMRT.

PMID- 30109574
TI  - Bioactivity evaluations of betulin identified from the bark of Betula platyphylla
      var. japonica for cancer therapy.
AB  - Identification of bioactive natural products with anticancer activity as well as
      alleviating effects on chemotherapy-induced side effects has significant
      implications for cancer treatment. Betula platyphylla var. japonica, commonly
      known as Asian white birch, has been used in Chinese traditional medicine for a
      variety of purposes. In this study, the medicinal properties of betulin from B.
      platyphylla var. japonica useful for cancer management were investigated. LC/MS
      analysis revealed that betulin is a main chemical component of the EtOH extract
      of B. platyphylla var. japonica bark, and betulin was isolated from EtOH extract
      using an LC/MS-guided isolation method. Its structure was identified with 1H and
      13C NMR spectroscopic data and LC/MS analysis and then compared to the previously
      reported spectroscopic and physical data. We first verified the cytotoxicity of
      betulin against three human lung adenocarcinoma cell lines, A549, H1264, and Calu
      6, with IC50 values ranging from 18.7 to 39.6 MUM. Regarding alleviation of side
      effects associated with anticancer chemotherapy, betulin ameliorated cisplatin
      induced renal cell damage to 80% of the control value from the concentration of 5
      MUM. In addition, betulin showed anti-gastritis activity against ethanol-induced
      gastric damage in rats and notably reduced the gastric damage index compared to
      control in a concentration-dependent manner. These findings provide the first
      experimental evidence for potential use of B. platyphylla var. japonica as a
      functional food for cancer treatment that simultaneously alleviates the side
      effects of chemotherapy.

PMID- 30109575
TI  - Cytoprotective effect of eupatilin against indomethacin-induced damage in feline
      esophageal epithelial cells: relevance of HSP27 and HSP70.
AB  - Indomethacin is a non-steroidal anti-inflammatory drug with clearly known side
      effects on the gastrointestinal tract. The purpose of the present study was to
      investigate whether eupatilin inhibit cell injury induced by indomethacin in
      cultured feline esophageal epithelial cells (EECs). EECs were used to investigate
      the ability of eupatilin to induce the expression of heat shock proteins (HSP27
      and HSP70) and analyze its cytoprotective effect against indomethacin-induced
      damage. The treatment of EECs with indomethacin for 8 h decreased cell viability.
      Western blot analysis showed that the levels of HSPs gradually decreased in cells
      treated with indomethacin, while eupatilin treatment increased the levels of
      HSPs. When treated with both indomethacin and eupatilin, the levels of HSPs
      increased rapidly, and were maintained at 130-140%. In addition, treatment with
      the specific inhibitors of PTK, PKC, PLC, p38 MAPK, JNKs, and PI3K attenuated the
      eupatilin-induced expression of HSPs. Pretreatment of EECs with the inhibitors of
      protein synthesis, actinomycin D or cycloheximide, attenuated the cytoprotective
      effect of eupatilin on indomethacin-induced cell damage. Reactive oxygen species
      production was upregulated by indomethacin, but downregulated by eupatilin. Taken
      together, it was suggested that HSPs were partly responsible for the eupatilin
      mediated cytoprotective activity against the indomethacin-induced damage in EECs.

PMID- 30109576
TI  - Fecal microbiota transplantation in a kidney transplant recipient with recurrent
      urinary tract infection.
AB  - PURPOSE: We report on a kidney transplant recipient treated with fecal microbiota
      transplantation (FMT) for recurrent urinary tract infections. METHODS: FMT was
      administered via frozen capsulized microbiota. Before and after FMT, urinary,
      fecal and vaginal microbiota compositions were analyzed. RESULTS: The patient
      remained without symptoms after FMT. CONCLUSIONS: Underlying mechanisms of action
      need to be addressed in depth by future research.

PMID- 30109577
TI  - A Simple Pre-endoscopy Score for Predicting Risk of Malignancy in Patients with
      Dyspepsia: A 5-Year Prospective Study.
AB  - BACKGROUND: The guidelines for performing endoscopy in dyspeptic patients based
      on clinical parameters alone have shown variable performance, and there is a need
      for better prediction tools. AIM: We aimed to prospectively develop and validate
      a simple clinical-cum-laboratory test-based scoring model to identify dyspeptic
      patients with high risk of upper gastrointestinal malignancy (UGIM). METHODS:
      Adult patients with dyspeptic symptoms were prospectively recruited over 5 years.
      Clinical details including alarm features were recorded, and blood tests for
      hemoglobin and albumin were done before endoscopy. The presence of UGIM was the
      primary outcome. Risk factors for UGIM were assessed, and based on the OR of
      significant factors, a predictive scoring model was constructed. ROC curve was
      plotted to identify optimal cutoff score. The model was validated using
      bootstrapping technique. RESULTS: The study included 2324 patients (41.9 +/- 12.8
      years; 33.4% females). UGIM was noted in 6.8% patients. The final model had
      following five positive predictors for UGIM-age > 40 years (OR 3.3, score 1);
      albumin <= 3.5 g% (OR 3.4, score 1); Hb <= 11 g% (OR 3.3, score 1); alarm
      features (OR 5.98, score 2); recent onset of symptoms (OR 8.7, score 3). ROC
      curve had an impressive AUC of 0.9 (0.88-0.93), and a score of 2 had 92.5%
      sensitivity in predicting UGIM. Validation by bootstrapping showed zero bias,
      which further strengthened our model. CONCLUSION: This simple clinical-cum
      laboratory test-based model performed very well in identifying dyspeptic patients
      at risk of UGIM. This can serve as a useful decision-making tool for referral for
      endoscopy.

PMID- 30109578
TI  - Survival Disparities by Race and Ethnicity in Early Esophageal Cancer.
AB  - BACKGROUND: Survival outcome disparities among esophageal cancer patients exist,
      but are not fully understood. AIMS: We used the Surveillance, Epidemiology, and
      End Results (SEER)-Medicare linked database to determine whether survival
      differences among racial/ethnic patient populations persist after adjusting for
      demographic and clinical characteristics. METHODS: Our study included T1-3N0M0
      adenocarcinoma and squamous cell cancer patients diagnosed between 2003 and 2011.
      We compared survival among two racial/ethnic patient subgroups using Cox
      proportional hazards methods, adjusting for age, sex, histology, marital status,
      socioeconomics, SEER region, comorbidities, T stage, tumor location, diagnosis
      year, and treatment received. RESULTS: Among 2025 patients, 87.9% were White and
      12.1% were Nonwhite. Median survival was 18.7 months for Whites vs 13.8 months
      for Nonwhites (p = 0.01). In the unadjusted model, Nonwhite patients had higher
      risk of mortality (HR = 1.29, 95% CI 1.11-1.49, p < 0.0001) when compared to
      White patients; however, in the Cox regression adjusted model there was no
      significant difference (HR = 0.94, 95% CI 0.80-1.10, p = 0.44). Surgery,
      chemotherapy, younger age, lower T stage, and lower Charlson comorbidity score
      were significant predictors in the full adjusted model. CONCLUSIONS: Differences
      in mortality risk by race/ethnicity appear to be largely explained by additional
      factors. In particular, associations were seen in surgery and T stage. Further
      research is needed to understand potential mechanisms underlying the differences
      and to better target patients who can benefit from treatment options.

PMID- 30109579
TI  - Prior Diagnosis of Barrett's Esophagus Is Infrequent, but Associated with
      Improved Esophageal Adenocarcinoma Survival.
AB  - BACKGROUND: Efforts to reduce mortality from esophageal adenocarcinoma (EA) have
      focused on screening and surveillance of Barrett's esophagus (BE). AIMS: We
      sought to determine the frequency of prior diagnosis of BE in patients with EA
      and to evaluate the impact of a prior BE diagnosis on mortality in EA patients.
      METHODS: This was a retrospective cohort study of patients diagnosed with EA in
      the VA during 2002-2016. We compared the distributions of EA stage and receipt of
      treatment between EA patients with and without a prior BE diagnosis and used Cox
      proportional hazards models to compare mortality risk (all-cause and cancer
      specific) unadjusted and adjusted for stage and treatment to assess their impact
      on any survival differences. RESULTS: Among 8564 EA patients, only 4.9% had a
      prior BE diagnosis. The proportion with prior BE diagnosis increased from 3.2% in
      EA patients diagnosed during 2005-2007 to 7.0% in those diagnosed during 2014
      2016. EA patients with a prior BE diagnosis were more likely to have stage 1
      disease and receive any treatment. A prior BE diagnosis was associated with lower
      all-cause mortality risk (hazard ratio [HR] unadjusted for stage, 0.69; 95% CI,
      0.61-0.80), which was largely explained by the earlier stage of EA at the time of
      diagnosis (HR adjusted for stage, 0.87; 95% CI, 0.75-0.99). There was no evidence
      of lead time bias or length time bias. CONCLUSIONS: Prior diagnosis of BE was
      associated with better survival, largely due to earlier EA stage at diagnosis.

PMID- 30109580
TI  - A Mismatch of Paradigms Disrupts the Introduction of Psycho-Educative
      Interventions for Families of Persons with SMI: An Interview Study with Staff
      from Community Services.
AB  - Treatment and support of people diagnosed with severe mental illness in Sweden
      takes place in out-patient psychiatric services or municipality services. Most of
      the responsibility for support in daily life are provided by the close family.
      One crucial matter is how to support these families. This research project aimed
      to investigate the Swedish construction with shared responsibility between county
      psychiatric care and municipality social care for consumers with severe mental
      illness affects actions in municipalities in relation to family support. Ten
      representatives from five municipality settings were interviewed. Five semi
      structured interviews were analysed using a thematic analysis. The following
      themes emerged; One overarching theme, "a mismatch of paradigms", and sub-themes:
      (a) "accentuating differences", (b) "doubts about including the entire family in
      the same session" and (c) "lack of a uniform family support policy". We conclude
      that a shared mandate needs a dialogue between psychiatric and municipality
      services concerning this mismatch.

PMID- 30109581
TI  - Development and Validation of the Therapist Barriers to Engaging Parents (TBEP)
      Measure.
AB  - Parent engagement is a well-documented challenge when delivering child and
      adolescent mental health treatments. Therapists' internal experiences, and how
      they respond to parents, may create a barrier to the parent engagement process.
      The current study developed the 13-item Therapist Barriers to Engaging Parents
      measure (TBEP) to assess providers' internal and external experiences that
      operate as barriers to parent engagement. The TBEP was completed by 148 child and
      family therapists across the United States. The TBEP demonstrated strong internal
      reliability (Cronbach alpha = .86), and was negatively correlated with counselor
      efficacy, and significantly positively correlated with burnout, indicating
      convergent validity. Incremental validity of the subscales of the TBEP was also
      demonstrated. The TBEP appears to be a psychometrically sound measure of the
      internal barriers mental health providers experience when trying to engage
      parents.

PMID- 30109582
TI  - From Physical Wellness to Cultural Brokering: Unpacking the Roles of Peer
      Providers in Integrated Health Care Settings.
AB  - This qualitative study explored peer provider experiences working in newly
      integrated mental health and primary care pilot programs within a large public
      mental health system. Nineteen peer providers participated in semistructured
      interviews that focused on experiences delivering care within integrated teams.
      Interviews were analyzed using constant comparative methods informed by grounded
      theory. Findings were organized into three themes that speak to variation in the
      definition and function of peers; lack of clarity in the peer role; and relating
      to other providers. Integrated settings need ongoing support to ensure clarity in
      the peer role and an inclusive work environment.

PMID- 30109583
TI  - Development and Implementation of Psychiatric Services in a Student-Operated
      Clinic.
AB  - This article chronicles the development and implementation of Monday Psychiatry
      Clinic, a psychiatry component of a medical student-operated free clinic (The
      Monday Clinic) in Dallas, Texas, providing assessment data systematically
      collected in the clinic. The established clinical purpose of Monday Psychiatry
      Clinic is to assess common psychiatric disorders and refer patients in need to
      appropriate sources of care. This clinic provided leadership education and
      volunteering opportunities to medical students who learned to interact with
      patients with psychiatric concerns, established clinical interviewing skills, and
      became familiar with psychiatric diagnostic criteria. More than one-third of the
      patients screened positive for depression, alcohol, or drug problems, and one
      fourth of the patients with a positive screen were diagnosed with one of these
      disorders. All patients with identified problems were referred for the
      appropriate level of care.

PMID- 30109584
TI  - Detection of Chlamydia trachomatis mRNA using digital PCR as a more accurate
      marker of viable organism.
AB  - Spontaneous resolution of urogenital Chlamydia trachomatis (CT) without treatment
      has previously been described, but a limitation of these reports is that DNA or
      RNA-based amplification tests used do not differentiate between viable infection
      and non-viable DNA. We modified a previously published CT mRNA detection (omp2)
      method to differentiate between viable infection and non-viable DNA in a sample
      of CT DNA PCR positive women. We modified a CT mRNA detection (omp2) method from
      reverse transcriptase qPCR (RTqPCR) to digital PCR (dPCR) and evaluated it in
      samples from CT DNA positive women. Firstly, CT infected McCoy B cells treated
      with azithromycin in vitro identified detectable mRNA levels disappeared <2 days,
      while DNA persisted up to 6 days. We used 55 self-collected vaginal swabs from a
      cohort of women diagnosed as DNA positive for chlamydia obtained pre- and 7 days
      of post-azithromycin treatment. Concordance with DNA results was higher for dPCR
      than RTqPCR (74.5% versus 65.5%). At visit 1, there was a strong linear
      relationship between DNA and mRNA (r = 0.9, p < 0.000); 24 samples had both mRNA
      and DNA detected (82.8%) and 5 had only DNA detected with a potential false
      positive proportion of 17.2% (95%CI: 5.8, 35.8). At visit 2, there was poor
      correlation between DNA and mRNA (r = 0.14, p = 0.55); eight specimens had only
      DNA detected (42.1%; 95%CI: 20.25, 66.50) and one had mRNA detected. DNA
      detection methods alone may detect non-viable DNA. Consideration should be given
      to further develop mRNA assays as ancillary tests to improve detection of viable
      chlamydia.

PMID- 30109585
TI  - Aiming to Improve Readmissions Through InteGrated Hospital Transitions
      (AIRTIGHT): a Pragmatic Randomized Controlled Trial.
AB  - BACKGROUND: Despite years of intense focus, inpatient and observation readmission
      rates remain high and largely unchanged. Hospitals have little, robust evidence
      to guide the selection of interventions effective at reducing 30-day readmissions
      in real-world settings. OBJECTIVE: To evaluate if implementation of recent
      recommendations for hospital transition programs is effective at reducing 30-day
      readmissions in a population discharged to home and at high-risk for readmission.
      DESIGN: A non-blinded, pragmatic randomized controlled trial ( Clinicaltrials.gov
      : NCT02763202) conducted at two hospitals in Charlotte, North Carolina. PATIENTS:
      A total of 1876 adult patients, under the care of a hospitalist, and at high risk
      for readmissions. INTERVENTION: Random allocation to a Transition Services (TS)
      program (n = 935) that bridges inpatient, outpatient, and home settings,
      providing patients virtual and in-person access to a dedicated multidisciplinary
      team for 30-days, or usual care (n = 941). MAIN MEASURE: Thirty-day, unplanned,
      inpatient, or observation readmission rate. KEY RESULTS: The 30-day readmission
      rate was 15.2% in the TS group and 16.3% in the usual care group (RR 0.93; 95%
      [CI, 0.76 to 1.15]; P = 0.52). There were no significant differences in
      readmissions at 60 and 90 days or in 30-day Emergency Department visit rates.
      Patients, who were referred to TS and readmitted, had less Intensive Care Unit
      admissions 15.5% vs. 26.8% (RR 0.74; 95% [CI, 0.59 to 0.93]; P = 0.02).
      CONCLUSIONS: An intervention inclusive of contemporary recommendations does not
      reduce a high-risk population's 30-day readmission rate. The high crossover to
      usual care (74.8%) reflects the challenge of non-participation that is ubiquitous
      in the real-world implementation of population health interventions. TRIAL
      REGISTRY: ClinicalTrials.gov ; registration ID number: NCT02763202, URL:
      https://clinicaltrials.gov/ct2/show/NCT02763202.

PMID- 30109587
TI  - Performance of Internists and Medicine Specialists in Medicare Quality Metrics:
      Variation by Specialty and Other Physician Characteristics.

PMID- 30109588
TI  - Effect and Safety of Huannao Yicong Formula () on Patients with Mild-to-Moderate
      Alzheimer's Disease: A Randomized, Double-Blinded, Donepezil-Controlled Trial.
AB  - OBJECTIVE: To assess the effect and safety of Huannao Yicong Formula (, HYF) in
      the treatment of patients with mild-to-moderate Alzheimer's disease (AD).
      METHODS: Sixty patients with mild-tomoderate AD were evenly randomized into HYF
      group and donepezil group with the random number method. Patients in the HYF
      group took 5 g of HYF granules twice daily and 5 mg placebo of donepezil once
      daily. Patients in the donepezil group took 5 mg donepezil once daily and 5 g
      placebo of HYF granules twice daily. The intervention lasted for 6 months.
      Clinical researchers, participants and statisticians were blinded to the
      treatment assignment throughout the study. The primary outcomes were scores of
      Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) and Chinese
      Medicine Symptom Scale (CM-SS). The secondary outcomes were scores of Montreal
      Cognitive Assessment (MoCA) test and Mini-Mental State Exam (MMSE). The serum
      levels of acetylcholinesterase (AchE) and amyloid-beta protein 42 (Abeta42) were
      detected with enzymelinked immunosorbent assay kits. The scale assessments were
      conducted at baseline, the 3rd and 6th months of treatment, respectively.
      Biochemistry tests were conducted at baseline and the 6th month of treatment.
      RESULTS: A total of 52 patients completed the trial, 28 in HYF group and 24 in
      donepezil group. Compared with the baseline, HYF and donepezil signifificantly
      decreased the total scores of ADAS-Cog and CM-SS, and signifificantly increased
      the scores of MoCA and MMSE after 6-month treatment (all P<0.01). Both treatments
      remarkably reduced the serum levels of AchE and Abeta42 (both P<0.05). The CM-SS
      total effective rate of HYF was signifificantly higher than donepezil [75.00%
      (21/28) vs. 54.17% (13/24), P<0.05]. No severe adverse events were observed in
      both groups. CONCLUSION: HYF is effective and safe for improving the cognitive
      function in mildto-moderate AD patients. [Trial registration: Chinese Clinical
      Trial Registry (Reg No. ChiCTR-IOR-17011746)].

PMID- 30109589
TI  - Whether Syndrome Differentiation Affects Treatment Result: Study Protocol of
      MaZiRenWan () for Functional Constipation in A Randomized Controlled Trial.
AB  - BACKGROUND: Syndrome is one of the most important concepts in Chinese medicine
      (CM) theory. However, it was not well accounted in most of randomized controlled
      trials (RCTs). OBJECTIVE: To determine whether CM syndrome differentiation
      affects the treatment results, functional constipation (FC) was selected as a
      target disease, and MaZiRenWan (, MZRW), a classic CM formula commonly used for
      constipation with excessive heat syndrome, was selected for study. METHODS: It is
      an 18-week prospective double-blinded, doubledummy RCT, including 2-week run-in,
      8-week treatment and 8-week post treatment follow-up. A total of 120 FC patients
      diagnosed as excessive heat syndrome will be recruited from the First Teaching
      Hospital of Tianjin University of Traditional Chinese Medicine and the Baokang
      Affifiliated Hospital of Tianjin University of Traditional Chinese Medicine.
      Patients will be randomly allocated into fixed MZRW (f_MZRW) granule group,
      modified MZRW (m_MZRW) granule group or bisacodyl group. For m_MZRW group, no
      more than two herbal granules can be added according to the syndrome
      differentiation for individual participants. The primary end point is the mean of
      complete spontaneous bowel movements (CSBMs) per week during the treatment
      period. Secondary end points include mean of CSBMs per week during follow-up,
      stool form, global symptom improvement, constipation and constipation-related
      symptoms assessment, CM syndrome change, and reported adverse events. DISCUSSION:
      This trial is designed to evaluate the effectiveness of these three interventions
      for FC patients with the CM syndrome of excessive heat, and to determine the
      change of CM syndrome and the progress of disease during the treatment course.
      The results are important to explore whether syndrome differentiation is
      important for the therapeutic effect of a formula on a disease. [Trial
      registration: Chinese Clinical Trial Registry (Reg No. ChiCTR-TRC-13003742);
      protocol version: MZRW/NSFC-81173363 (2015.05.04)].

PMID- 30109586
TI  - Interventions to Increase Depression Treatment Initiation in Primary Care
      Patients: a Systematic Review.
AB  - INTRODUCTION: Nearly 50% of depressed primary care patients referred to mental
      health services do not initiate mental health treatment. The most promising
      interventions for increasing depression treatment initiation in primary care
      settings remain unclear. METHODS: We performed a systematic search of publicly
      available databases from inception through August 2017 to identify interventions
      designed to increase depression treatment initiation. Two authors independently
      selected, extracted data, and rated risk of bias from included studies. Eligible
      studies used a randomized or pre-post design and assessed depression treatment
      initiation (i.e., >= 1 mental health visit or antidepressant fill) among adults,
      the majority of whom met criteria for depression. Interventions were classified
      as simple or complex and sub-classified into intervention strategies that were
      graded for strength of evidence. RESULTS: Of 9516 articles identified, we
      included 14 unique studies representing 16 (4 simple and 12 complex)
      interventions and 8 treatment initiation strategies. We found low to moderate
      strength of evidence for collaborative/integrated care (3 studies), treatment
      preference matching (2 studies), and case management (2 studies) strategies.
      However, there was insufficient evidence to determine the benefit of cultural
      tailoring (2 studies), motivation (alone, with reminders or with cultural
      tailoring (5 studies)), education (1 study), and shared decision-making
      strategies (1 study). Overall, we found moderate strength of evidence for complex
      interventions (8 of 12 complex interventions demonstrated statistically
      significant effects on treatment initiation). DISCUSSION:
      Collaborative/integrated care, preference treatment matching, and case management
      strategies had the best evidence for improving depression treatment initiation,
      but none of the strategies had high strength of evidence. While primary care
      settings can consider using some of these strategies when referring depressed
      patients to treatment, our review highlights the need for further rigorous
      research in this area.

PMID- 30109591
TI  - Joseph P. Kriss, MD (1915-1989).

PMID- 30109590
TI  - Aflatoxin M1 levels in different marketed milk products in Nairobi, Kenya.
AB  - Milk is an important source of energy and nutrients, especially for children, and
      in Kenya, milk consumption is higher than other countries in the region. One
      major concern with milk is the risks of chemical contaminants, and reports of
      high levels of aflatoxin M1 (AFM1) in milk in Kenya has been causing public
      health concerns. This study collected marketed milk products every month during 1
      year, just as a consumer would purchase them from retailers and traders in a low
      income area, and a major supermarket in a middle/high-income area. In total, 291
      sampled milk products (raw, pasteurised, UHT milk, yoghurt and lala) were
      collected and analysed for AFM1 using a commercial ELISA kit. More than 50% of
      the samples exceeded 50 ng/kg (the level allowed in the EU), but only three
      samples exceeded 500 ng/kg (the level allowed in the USA). Geometric mean AFM1
      level was 61.9 ng/kg in the 135 samples from the low-income area while it was
      36.1 ng/kg in the 156 from the higher income area (p < 0.001). The levels varied
      significantly depending on the time of year, with lowest levels of milk in
      January. There were also differences between manufacturers and products, with UHT
      milk having lower levels. There was no difference depending on the price for all
      dairy products, but when only including milk, higher price was associated with
      lower levels of AFM1. In conclusion, this study shows that milk purchased by a
      consumer is likely to contain AFM1 above 50 ng/kg, and that further research is
      needed to find ways to mitigate AFM1 contamination through working with farmers
      and milk processors both in the formal and informal sectors.

PMID- 30109592
TI  - "Apical thinning": Relations between myocardial wall thickness and apical left
      ventricular tracer uptake as assessed with positron emission tomography
      myocardial perfusion imaging.
AB  - BACKGROUND: A reduction in left ventricular apical tracer uptake (apical
      thinning) is frequently observed in myocardial perfusion imaging (MPI), yet its
      cause remains a matter of debate, particularly in perfusion emission tomography
      (PET). This analysis sought to determine whether apical thinning in PET-MPI is
      attributable to true anatomical thinning of the left ventricular apical
      myocardium. METHODS AND RESULTS: We retrospectively analyzed 57 patients without
      any history or signs of apical myocardial infarction who underwent rest PET-MPI
      with 13N-ammonia and contrast-enhanced cardiac computed tomography (CT). Semi
      quantitative normalized percent apical 13N-ammonia uptake at rest, myocardial
      blood flow (MBF), and k2 wash-out rate constants were compared to apical
      myocardial wall thickness measurements derived from CT and base-to-apex gradients
      were calculated. Apical thinning was found in 93% of patients and in 74% when
      analysis of normalized apical tracer uptake was confined to end-systole. No
      significant correlation was found between apical myocardial thickness and apical
      tracer uptake (r = - 0.080, P = .553), MBF (r = - 0.211, P = .115), or k2 wash
      out rate (r = - 0.023, P = .872), nor between apical myocardial thickness and any
      gradients. A statistically significant but small difference in apical myocardial
      thickness was observed in patients with moderately to severely reduced apical
      tracer uptake vs patients with normal to mildly reduced uptake (4.3 +/- 0.7 mm vs
      4.7 +/- 0.7 mm; P = .043). CONCLUSIONS: Apical thinning is a highly prevalent
      finding during 13N-ammonia PET-MPI that is not solely attributable to true
      anatomical apical wall thickness or the partial volume effect. Other factors that
      yet need to be identified seem to have a more prominent impact.

PMID- 30109593
TI  - Clinical significance of quantitative assessment of glucose utilization in
      patients with ischemic cardiomyopathy.
AB  - BACKGROUND: The aim of this study was to prospectively quantify the rate of
      myocardial glucose uptake (MRGlu) in myocardium with different perfusion
      metabolism patterns and determine its prognostic value in patients with ischemic
      cardiomyopathy. METHODS AND RESULTS: 79 patients with ischemic cardiomyopathy
      were prospectively enrolled for dynamic cardiac FDG PET, and then followed for at
      least 6 months. Perfusion-metabolism patterns were determined based on visual
      score analysis of 201Tl SPECT and FDG PET. MRGlu was analyzed using the Patlak
      kinetic model. The primary end-point was cardiovascular mortality. Significantly
      higher MRGlu was observed in viable compared with non-viable areas. Negative
      correlations were found between MRGlu in transmural match and a history of
      hyperlipidemia, statin usage, and triglyceride levels. Diabetic patients
      receiving dipeptidyl peptidase-4 inhibitors (DPP4i) had a significantly lower
      MRGlu in transmural match, mismatch, and reverse mismatch. Patients with MRGlu in
      transmural match >= 23.40 or reverse mismatch >= 36.90 had a worse outcome.
      CONCLUSIONS: Myocardial glucose utilization was influenced by substrates and
      medications, including statins and DPP4i. MRGlu could discriminate between viable
      and non-viable myocardium, and MRGlu in transmural match and reverse mismatch may
      be prognostic predictors of cardiovascular death in patients with ischemic
      cardiomyopathy.

PMID- 30109594
TI  - FDG PET/CT for the diagnosis and management of infective endocarditis: Expert
      consensus vs evidence-based practice.

PMID- 30109595
TI  - Rosai-Dorfman disease and left ventricular noncompaction cardiomyopathy: A heart
      failure conundrum.

PMID- 30109596
TI  - A quick glance at selected topics in this issue.
AB  - "A quick glance at selected topics in this issue" aims to highlight contents of
      the Journal and provide a quick review to the readers.

PMID- 30109597
TI  - Striato-nigro-striatal tract dispersion abnormalities in patients with chronic
      schizophrenia.
AB  - The white matter connections between the midbrain dopamine neurons and the
      striatum are part of a neural system involved in reward-based learning, a process
      that is impaired in patients with schizophrenia. The striato-nigro-striatal (SNS)
      tract, which participates in this process, has not as yet been explored. The
      present study aimed to use diffusion MRI (dMRI) to delineate the SNS tract, and
      to compare the application of two dMRI measures, Tract Dispersion (TD), an index
      of white matter morphology, and Fractional Anisotropy (FA), an index of white
      matter integrity, to detect group differences between patients with chronic
      schizophrenia (CSZ) and healthy controls (HC). dMRI scans were acquired in 22
      male patients with CSZ and 23 age-matched HC. Two-tensor tractography was used in
      addition to manually-delineated regions of interest to extract the SNS tract. A
      mixed-model analysis of variance was used to investigate differences in TD and FA
      between CSZ patients and HC. The associations between TD and behavioral measures
      were also explored. Patients and controls differed significantly in TD (P =
      0.04), but not in FA (P = 0.69). The group differences in TD were driven by a
      higher TD in the right hemisphere in the CSZ group. Higher TD correlated
      significantly with poorer performance in the Iowa Gambling Task (IGT) when
      combining the scores of both groups. The findings suggest that dysconnectiviy of
      the SNS tract which is associated with schizophrenia, could arise from
      abnormalities in white matter morphology. These abnormalities may potentially
      reflect irregularities in brain development.

PMID- 30109598
TI  - Improving communication, teamwork, and action during a "cannot intubate cannot
      oxygenate (CICO)" emergency: employing CICO as a cognitive aid mnemonic.

PMID- 30109599
TI  - A rare cause of reversible gastric outlet obstruction.

PMID- 30109601
TI  - Common Genetic Variants Link the Abnormalities in the Gut-Brain Axis in
      Prematurity and Autism.
AB  - This review considers a link between prematurity and autism by comparing
      symptoms, physiological abnormalities, and behavior. It focuses on the
      bidirectional signaling between the microbiota and the brain, here defined as the
      microbiota-gut-vagus-heart-brain (MGVHB) axis and its systemic disruption
      accompanying altered neurodevelopment. Data derived from clinical and animal
      studies document increased prevalence of gastrointestinal, cardiovascular,
      cognitive, and behavioral symptoms in both premature and autistic children and
      suggest an incomplete maturation of the gut-blood barrier resulting in a "leaky
      gut," dysbiosis, abnormalities in vagal regulation of the heart, altered
      development of specific brain regions, and behavior. Furthermore, this review
      posits the hypothesis that common genetic variants link the abnormalities in the
      MGVHB axis in premature and autistic pathologies. This hypothesis is based on the
      recently identified common genetic variants: early B cell factor 1 (EBF1),
      selenocysteine tRNA-specific eukaryotic elongation factor (EEFSEC), and
      angiotensin II receptor type 2 (AGTR2), in the maternal and infant DNA samples,
      associated with risk of preterm birth and independently implicated in a risk of
      autism. We predict that the AGTR2 variants involved in the brain maturation and
      oxytocin-arginine-vasopressin (OXT-AVP) pathways, related to social behavior,
      will contribute to our understanding of the link between prematurity and autism
      paving a way to new therapies.

PMID- 30109602
TI  - Determination of the 3D Genome Organization of Bacteria Using Hi-C.
AB  - The spatial organization of genomes is based on their hierarchical
      compartmentalization in topological domains. There is growing evidence that
      bacterial genomes are organized into insulated domains similar to the
      Topologically Associating Domains (TADs) detected in eukaryotic cells. Chromosome
      conformation capture (3C) technologies are used to analyze in vivo DNA proximity
      based on ligation of distal DNA segments crossed-linked by bridging proteins. By
      combining 3C and high-throughput sequencing, the Hi-C method reveals genome-wide
      interactions within topological domains and global genome structure as a whole.
      This chapter provides detailed guidelines for the preparation of Hi-C sequencing
      libraries for bacteria.

PMID- 30109600
TI  - A study of association between regulatory polymorphism in the IL-10 gene promoter
      region and acute viral hepatitis, and acute liver failure.
AB  - BACKGROUND: The level of inflammatory cytokine Interleukin (IL)-10 is increased
      in patients infected with hepatitis-related acute liver failure (ALF), and this
      was thought to be because of the regulatory polymorphism in the IL-10 gene
      promoter region. The present study was designed to analyze the possible
      association between IL-10 gene promoter polymorphism and acute viral hepatitis
      (AVH), and ALF. An attempt was made to quantify IL-10 levels at admission, during
      the hospital stay, and at the final outcome to study its relationship with liver
      injury among patients with AVH, ALF, and controls. METHODS: The study included 40
      patients each with ALF and AVH. IL-10 gene promoter polymorphism was detected by
      the PCR-RFLP method. Quantification of IL-10 was done using commercially
      available ELISA kits. RESULTS: The individuals with -592 AC, -819 TC, -1082 AA
      genotypes were found to have a significantly higher risk of ALF whereas those
      with -592 AA and - 819 CC polymorphism were found to be less susceptible.
      Individuals with - 819 CC were found to be more susceptible to AVH while those
      with -592 AA and -819 TT were less susceptible as compared to controls. Mean
      serum IL-10 at admission was significantly elevated in patients with ALF (38.4+/
      11.3 pg/mL) as compared to patients with AVH (16.7+/-5.4 pg/mL) and control
      population (8.3+/-3.6 pg/mL, p < 0.05). CONCLUSION: Regulatory polymorphism in
      the IL-10 gene promoter has a possible and significant association with severity
      and outcome in patients with AVH and ALF. Raised levels of IL-10 could be
      predictive of prognosis in patients with ALF.

PMID- 30109603
TI  - Processing and Analysis of Hi-C Data on Bacteria.
AB  - The study of three-dimensional genome organization has recently gained much
      attention in the context of novel techniques for detecting genome-wide contacts
      using next-generation sequencing. These genome-wide chromosome conformation
      capture-based methods, such as Hi-C, give a deep topological insight into the
      architecture of the genome inside the cell. This chapter reviews the steps to
      process next-generation Hi-C sequencing data to generate a final contact
      probability map. We describe these steps using publicly available Hi-C datasets
      of different bacteria. We also present strategies to assess the quality of Hi-C
      datasets.

PMID- 30109604
TI  - GeF-seq: A Simple Procedure for Base Pair Resolution ChIP-seq.
AB  - Nucleotide sequences recognized and bound by DNA-binding proteins (DBPs) are
      critical to control and maintain gene expression, replication, chromosome
      segregation, cell division, and nucleoid structure in bacterial cells. Therefore,
      determination of the binding sequences of DBPs is important not only to study DBP
      recognition mechanisms, but also to understand the fundamentals of cell
      homeostasis. While ChIP-seq analysis appears to be an effective way to determine
      DBP-binding sites on the genome, the resolution is sometimes not sufficient to
      identify the sites precisely. Here, we introduce a simple and effective method
      named Genome footprinting with high-throughput sequencing (GeF-seq) to determine
      binding sites of DBPs at single base-pair resolution. GeF-seq detects binding
      sites of DBPs as sharp peaks and thus makes it possible to identify the
      recognition sequence in each "binding peak" more easily and accurately than using
      ChIP-seq.

PMID- 30109605
TI  - Genomic SELEX Screening of Regulatory Targets of Escherichia coli Transcription
      Factors.
AB  - The genome of Escherichia coli K-12 is transcribed by a single species of RNA
      polymerase. The selectivity of its transcriptional targets is modulated via two
      steps of protein-protein interaction: at the first step, seven species of the
      sigma subunit are involved, at the second step, a total of approximately 300
      species of transcription factor (TFs). For the identification of the regulatory
      targets of these two groups of regulatory proteins, we developed two in vitro
      approaches, "Genomic SELEX" (currently designated as gSELEX) and "PS (promoter
      specific)-TF" screenings. Here, we describe a detailed protocol of the genomic
      SELEX screening system which uses purified regulatory proteins and fragments of
      genomic DNA from E. coli.

PMID- 30109606
TI  - Modular Assembly of Synthetic Secondary Chromosomes.
AB  - The development of novel DNA assembly methods in recent years has paved the way
      for the construction of synthetic replicons to be used for basic research and
      biotechnological applications. Questions of how chromosomes need to be
      constructed to maintain the genetic information can now be answered by a learning
      by-building approach. Here, we describe an efficient pipeline for the design and
      assembly of synthetic, secondary chromosomes in Escherichia coli based on the
      popular Modular Cloning system (MoClo).

PMID- 30109607
TI  - High-Resolution Characterization of DNA/Protein Complexes in Living Bacteria.
AB  - The occurrence of DNA looping is ubiquitous. This process plays a well-documented
      role in the regulation of prokaryotic gene expression, such as the Escherichia
      coli lactose (lac) operon. Here, we present two complementary methods for high
      resolution in vivo detection of DNA/protein binding within the bacterial nucleoid
      by using either chromatin immunoprecipitation combined with phage lambda
      exonuclease digestion (ChIP-exo) or chromatin endogenous cleavage (ChEC), coupled
      with ligation-mediated polymerase chain reaction (LM-PCR) and Southern blot
      analysis. As an example we apply these in vivo protein-mapping methods to E. coli
      to show direct binding of architectural proteins in the Lac repressor-mediated
      DNA repression loop.

PMID- 30109609
TI  - Genetic Approaches to Study the Interplay Between Transcription and Nucleoid
      Associated Proteins in Escherichia coli.
AB  - Bacterial nucleoid-associated proteins are important in nucleoid-structuring,
      homeostasis of DNA supercoiling, and in regulation of transcription. Vice versa,
      transcription influences DNA supercoiling and possibly DNA-binding of nucleoid
      associated proteins. Here, I describe genetic tools to study the interplay
      between transcription and nucleoid-associated proteins such as H-NS in
      Escherichia coli. These standard methods include construction of genomic promoter
      reporter gene fusions to study regulation of promoters, genome insertion of
      promoter cassettes to drive expression of a gene of interest, and construction of
      isogenic hns mutants and precautions when doing so.

PMID- 30109608
TI  - Imaging of Transcription and Replication in the Bacterial Chromosome with
      Multicolor Three-Dimensional Superresolution Structured Illumination Microscopy.
AB  - Superresolution imaging technology has contributed to our understanding of the
      subnucleoid organization in E. coli cells. Multicolor superresolution images
      revealing "bacterial nucleolus-like structure or organization," "nucleolus-like
      compartmentalization of the transcription factories," and "spatial segregation of
      the transcription and replication machineries" have enhanced our understanding of
      the dynamic landscape of the bacterial chromatin. This chapter provides a brief
      introduction into multicolor three-dimensional superresolution structured
      illumination microscopy (3D-SIM) used to study the spatial organization of the
      transcription machinery and its spatial relationship with replisomes from a
      microbiological research perspective. In addition to a detailed protocol,
      practical considerations are discussed in relation to (1) sampling and treatment
      of cells containing fluorescent fusion proteins, (2) imaging the transcription
      and replication machineries at single-cell levels, (3) performing imaging
      experiments to capture the spatial organization of the transcription machinery
      and the nucleoid, and (4) image acquisition and analysis.

PMID- 30109610
TI  - Atomic Force Microscopy Imaging and Analysis of Prokaryotic Genome Organization.
AB  - This protocol describes the application of atomic force microscopy for structural
      analysis of the prokaryotic and organellar nucleoids. It is based on a simple
      cell manipulation procedure that enables step-wise dissection of the nucleoid.
      The procedure includes (1) on-substrate-lysis of cells, and (2) enzyme treatment,
      followed by atomic force microscopy. This type of dissection analysis permits
      analysis of nucleoid structure ranging from the fundamental units assembled on
      DNA to higher order levels of organization. The combination with molecular
      genetic and biochemical techniques further permits analysis of the functions of
      key nucleoid factors relevant to signal-induced structural re-organization or
      building up of basic structures, as seen for Dps in Escherichia coli, and TrmBL2
      in Thermococcus kodakarensis. These systems are described here as examples of the
      successful application of AFM for this purpose. Moreover, we describe the
      procedures needed for quantitative analysis of the data.

PMID- 30109611
TI  - Dynamic Light Scattering of DNA-Ligand Complexes.
AB  - Dynamic Light Scattering ( DLS ) enables the characterization of sizes and
      electrokinetic properties of colloids, polymers, macromolecules. DNA is a charged
      semiflexible polyelectrolyte, which is condensed or compacted by counterions,
      proteins, and other condensing agents in processes such as chromosome compaction
      and gene therapeutic applications. DNA condensation is closely related to charge
      screening, since packaging requires effective neutralization of its surface
      negative charges. In this chapter, we describe in detail the protocol for DLS of
      DNA-ligand complexes. As an example, we describe data for condensation of DNA by
      chitosan and the measurement of size, zeta potential, and electrophoretic
      mobility of the DNA-ligand complex by DLS.

PMID- 30109612
TI  - Microscale Thermophoresis Analysis of Chromatin Interactions.
AB  - Architectural DNA-binding proteins are key to the organization and compaction of
      genomic DNA inside cells. The activity of architectural proteins is often subject
      to further modulation and regulation through the interaction with a diverse array
      of other protein factors. Detailed knowledge on the binding modes involved is
      crucial for our understanding of how these protein-protein and protein-DNA
      interactions shape the functional landscape of chromatin in all kingdoms of life:
      bacteria, archaea, and eukarya.Microscale thermophoresis (MST) is a biophysical
      technique that has seen increasing application in the study of biomolecular
      interactions thanks to its solution-based nature, its rapid application, modest
      sample demand, and the sensitivity of the thermophoresis effect to binding
      events. Here, we describe the use of MST in the study of chromatin interactions,
      with emphasis on the wide range of ways in which these experiments are set up and
      the diverse types of information they reveal. These aspects are illustrated with
      four very different systems: the sequence-dependent DNA compaction by
      architectural protein HMfB; the sequential binding of core histone complexes to
      histone chaperone APLF; the impact of the nucleosomal context on the recognition
      of histone modifications; and the binding of a LANA-derived peptide to nucleosome
      core. Special emphasis is given to the key steps in the design, execution, and
      analysis of MST experiments in the context of the provided examples.

PMID- 30109613
TI  - Quantitative Determination of DNA Bridging Efficiency of Chromatin Proteins.
AB  - DNA looping is important for genome organization in all domains of life. The
      basis of DNA loop formation is the bridging of two separate DNA double helices.
      Detecting DNA bridge formation generally involves the use of complex single
      molecule techniques (atomic force microscopy, magnetic, or optical tweezers).
      Although DNA bridging can be qualitatively described, quantification of DNA
      bridging and bridging dynamics using these techniques is challenging. Here, we
      describe a novel biochemical assay capable of not only detecting DNA bridge
      formation, but also allowing for quantification of DNA bridging efficiency and
      the effects of physico-chemical conditions on DNA bridge formation.

PMID- 30109614
TI  - Approaches for Determining DNA Persistence Length Using Atomic Force Microscopy.
AB  - Atomic force microscopy (AFM) is widely used to image and study biological
      molecules. As an example, we have utilized AFM to investigate how the mechanical
      properties of DNA polymers depend on electrostatics and the strength of DNA base
      stacking by studying double-stranded DNA molecules incorporating several
      different neutral and charged base modifications. Here, we describe ten
      complementary approaches for determining DNA persistence length by AFM imaging.
      The combination of different approaches provides increased confidence and
      statistical reliability over existing methods utilizing only a single approach.

PMID- 30109615
TI  - Quantitation of DNA-Binding Affinity Using Tethered Particle Motion.
AB  - The binding constant is an important characteristic of a DNA-binding protein. A
      large number of methods exist to measure the binding constant, but many of those
      methods have intrinsic flaws that influence the outcome of the characterization.
      Tethered Particle Motion (TPM) is a simple, cheap, and high-throughput single
      molecule method that can be used to reliably measure binding constants of
      proteins binding to DNA, provided that they distort DNA. In TPM, the motion of a
      bead tethered to a surface by DNA is tracked using light microscopy. A protein
      binding to the DNA will alter bead motion. This makes it possible to measure
      binding properties. We use the bacterial protein Integration Host Factor (IHF) as
      an example to show how specific binding to DNA can be measured. Moreover, we show
      a new intuitive quantitative approach to displaying data obtained via TPM.

PMID- 30109617
TI  - Unraveling the Biophysical Properties of Chromatin Proteins and DNA Using
      Acoustic Force Spectroscopy.
AB  - Acoustic Force Spectroscopy (AFS) is a single-molecule micromanipulation
      technique that uses sound waves to exert force on surface-tethered DNA molecules
      in a microfluidic chamber. As large numbers of individual protein-DNA complexes
      are tracked in parallel, AFS provides insight into the individual properties of
      such complexes as well as their population averages. In this chapter, we describe
      in detail how to perform AFS experiments specifically on bare DNA, protein-DNA
      complexes, and how to extract their (effective) persistence length and contour
      length from force-extension relations.

PMID- 30109616
TI  - Observing Bacterial Chromatin Protein-DNA Interactions by Combining DNA Flow
      Stretching with Single-Molecule Imaging.
AB  - Nucleoid-associated proteins bind to DNA specifically and nonspecifically to
      perform various roles in chromosome organization and segregation. In this
      chapter, we describe how the interaction between nucleoid-associated proteins and
      flow-stretched DNAs can be visualized on the single-molecule level. We describe
      three different experimental schemes that allow one to directly observe how these
      proteins that make up bacterial chromatin, associate with and act on DNAs. First,
      we describe how to visualize the diffusion of fluorescently labeled proteins on
      flow stretched DNAs. Second, we describe how the binding of bacterial chromatin
      proteins can be correlated with DNA condensation. Lastly, we describe the DNA
      motion capture assay, which allows one to probe the mechanism of DNA condensation
      by tracking how different segments of a flow stretched DNA are compacted by
      bacterial chromatin proteins.

PMID- 30109618
TI  - Unraveling DNA Organization with Single-Molecule Force Spectroscopy Using
      Magnetic Tweezers.
AB  - Genomes carry the genetic blueprint of all living organisms. Their organization
      requires strong condensation as well as carefully regulated accessibility to
      specific genes for proper functioning of their hosts. The study of the structure
      and dynamics of the proteins that organize the genome has benefited tremendously
      from the development of single-molecule force spectroscopy techniques that allow
      for real-time, nanometer accuracy measurements of the compaction of DNA and
      manipulation with pico-Newton scale forces. Magnetic tweezers in particular have
      the unique ability to complement such force spectroscopy with the control over
      the linking number of the DNA molecule, which plays an important role when DNA
      organizing proteins form or release wraps, loops, and bends in DNA. Here, we
      describe all the necessary steps to prepare DNA substrates for magnetic tweezers
      experiments, assemble flow cells, tether DNA to magnetics bead inside flow cell,
      and manipulate and record the extension of such DNA tethers. Furthermore, we
      explain how mechanical parameters of nucleo-protein filaments can be extracted
      from the data.

PMID- 30109619
TI  - In Vitro Transcription Assay to Quantify Effects of H-NS Filaments on RNA Chain
      Elongation by RNA Polymerase.
AB  - While structuring of the bacterial nucleoid by nucleoid-associated proteins
      (NAPs) is critical for proper chromosomal organization and compaction, DNA
      dependent RNA polymerase (RNAP) must frequently interact with and overcome the
      barriers these NAPs impose upon transcription. One particular NAP in Escherichia
      coli that influences transcription is the histone-like nucleoid structuring
      protein, H-NS, that binds to DNA and forms nucleoprotein filaments. To
      specifically investigate the effect that H-NS filaments have on RNAP elongation,
      we developed an in vitro transcription assay to assess transcript elongation by
      RNAP when transcribing DNA bound by an H-NS filament. In this method, initiation
      and elongation by RNAP are uncoupled by initiating transcription in the presence
      of three rNTPs to halt elongation just downstream of the promoter. Before
      elongation is restarted, an H-NS filament is formed so that elongation occurs on
      an H-NS nucleoprotein filament template. We also describe visualization and
      analysis of the transcription products from the nucleoprotein template which
      provides insight into how H-NS and RNAP interact. This method is a starting point
      to determine effects of NAPs on RNAP elongation in a variety of conditions.

PMID- 30109620
TI  - Deciphering 3D Organization of Chromosomes Using Hi-C Data.
AB  - In order to interpret data from Hi-C studies genome-wide contact probability maps
      need to be translated into models of functional 3D genome organization. Here, we
      first present an overview of computational methods to analyze contact probability
      maps in terms of features such as the level and shape of compartmentalization.
      Next, we describe approaches to modeling 3D genome organization based on Hi-C
      data.

PMID- 30109621
TI  - Molecular Dynamics Simulation of a Feather-Boa Model of a Bacterial Chromosome.
AB  - The chromosome of a bacterium consists of a mega-base pair long circular DNA,
      which self-organizes within the micron-sized bacterial cell volume, compacting
      itself by three orders of magnitude. Unlike in eukaryotes, it lacks a nuclear
      membrane, and freely floats in the cytosol confined by the cell membrane. It is
      believed that strong confinement, cross-linking by associated proteins, and
      molecular crowding all contribute to determine chromosome size and morphology.
      Modeling the chromosome simply as a circular polymer decorated with closed side
      loops in a cylindrical confining volume, has been shown to already recapture some
      of the salient properties observed experimentally. Here, we describe how a
      computer simulation can be set up to study structure and dynamics of bacterial
      chromosomes using this model.

PMID- 30109622
TI  - Advancement of Biotechnology by Genetic Modifications.
AB  - One of the greatest sources of metabolic and enzymatic diversity are
      microorganisms. In recent years, emerging recombinant DNA and genomic techniques
      have facilitated the development of new efficient expression systems,
      modification of biosynthetic pathways leading to new metabolites by metabolic
      engineering, and enhancement of catalytic properties of enzymes by directed
      evolution. Complete sequencing of industrially important microbial genomes is
      taking place very rapidly, and there are already hundreds of genomes sequenced.
      Functional genomics and proteomics are major tools used in the search for new
      molecules and development of higher-producing strains.

PMID- 30109624
TI  - Carotenoids: From Plants to Food and Feed Industries.
AB  - In this review, carotenoids from plants are described, and their natural
      existence is addressed. Carotenoids are 40-carbon isoprenoid molecules that
      produce the red, yellow, and orange pigmentation found in nature. Various plants,
      microalgae, bacteria, and fungi are natural sources of carotenoids and are
      presented in detail. The chemistry of carotenoids and their classification is
      also described along with the effect of carotenoids on human health which is
      explained with focus on lutein-zeaxanthin, astaxanthin, canthaxanthin,
      capsanthin, and lycopene. Clinical studies suggest that carotenoid consumption is
      associated with lower risk of cardiovascular disease, cancer, and eye disease.
      Finally, another issue discussed is the role of carotenoids in animals and their
      feed with focus on birds, fish and crustaceans, livestock, and poultry.

PMID- 30109623
TI  - Carotenoids Production: A Healthy and Profitable Industry.
AB  - Carotenoids relevance as natural pigments is mainly due to their uses as
      colorants, feed supplements, nutraceuticals and for medical, cosmetic, and
      biotechnological purposes. Since they have putative health beneficial effects,
      the demand and market of carotenoids are growing significantly. There is a
      diversity of natural and synthetic carotenoids, but only a few of them are
      commercially produced, including carotenes (beta-carotene and lycopene) and
      xanthophylls (astaxanthin, canthaxanthin, lutein, zeaxanthin, and capsanthin).
      Some biotechnological processes for carotenoids production were established some
      years ago, but new strains and technologies are being developed nowadays for
      carotenoids widely in demand. This chapter shows a revision of the main
      carotenoids from a commercial point of view.

PMID- 30109625
TI  - Express Analysis of Microalgal Secondary Carotenoids by TLC and UV-Vis
      Spectroscopy.
AB  - We elucidate the peculiarities of express analysis of secondary carotenoids from
      microalgae and their preliminary identification using TLC and UV-Vis spectroscopy
      with emphasis on biotechnologically significant producers of the value-added
      pigment astaxanthin. Advantages and limitations of the method are described to
      underline the value of TLC as a potential companion method to mainstream
      separation techniques such as HPLC. Special attention is paid to common errors
      and pitfalls of the method and possible work-arounds, as well as to overall
      strategy of the analysis, sample preparation, and material selection.

PMID- 30109626
TI  - Batch Cultivation for Astaxanthin Analysis Using the Green Microalga Chlorella
      zofingiensis Under Multitrophic Growth Conditions.
AB  - Astaxanthin represents a high-value ketocarotenoid that has been gaining great
      attention from both the science and public communities in recent years.
      Microalgae are the primary source of natural astaxanthin. Chlorella zofingiensis,
      a freshwater and oleaginous green microalga, is capable of growing well
      photoautotrophically, heterotrophically, and mixotrophically for high-density
      biomass and astaxanthin production. Here we describe the astaxanthin production
      pipeline using C. zofingiensis as cell factories under different trophic
      conditions, including strain preparation, inoculation, and cultivation, biomass
      harvest and dewatering, and astaxanthin extraction, determination, and
      quantification.

PMID- 30109627
TI  - Preparative Recovery of Carotenoids from Microalgal Biomass.
AB  - Carotenoids are widespread substances with important physiological roles, and
      some of them, such as lutein, astaxanthin, or vaucherioxanthin, are high-value
      products that can be used as high-quality food color and antioxidants, and some
      have an alleged role in the prevention of disorders such as AMD. Carotenoid
      extracts are currently obtained from plant sources, but microalgae have been
      demonstrated to be a competitive source likely to become an alternative. The
      extraction of carotenoids from microalgae possesses specific problems that arise
      from the different structure and composition of the source biomass. Here is
      presented a method for the recovery of carotenoid extracts from microalgal
      biomass in the kilogram scale.

PMID- 30109628
TI  - Adaptive Laboratory Evolution for Enhanced Carotenoid Production in Microalgae.
AB  - In order to produce natural pigments with competitive prices, algal strains
      employed in industrial production need to be improved for increasing the
      productivity of valuable metabolites, thereby reducing the overall production
      cost. Adaptive laboratory evolution (ALE) is a traditional method for strain
      improvement, which has been effectively utilized in bacteria and fungi. With the
      growing interest in algal biotechnology, attempts have recently been put forward
      to improve microalgal strains with ALE approach. This chapter describes a
      stepwise adaptive evolution strategy that enhances carotenoid yield from
      microalgae.

PMID- 30109629
TI  - Carotenoid Production by Recombinant Corynebacterium glutamicum: Strain
      Construction, Cultivation, Extraction, and Quantification of Carotenoids and
      Terpenes.
AB  - Corynebacterium glutamicum is a workhorse of industrial amino acid production
      employed for more than five decades for the million-ton-scale production of L
      glutamate and L-lysine. This bacterium is pigmented due to the biosynthesis of
      the carotenoid decaprenoxanthin. Decaprenoxanthin is a carotenoid with 50 carbon
      atoms, and, thus, C. glutamicum belongs to the rare group of bacteria that
      produce long-chain C50 carotenoids. C50 carotenoids have been mainly isolated
      from extremely halophilic archaea (Kelly and Jensen, Acta Chem Scand 21:2578,
      1967; Pfander, Pure Appl Chem 66:2369-2374, 1994) and from Gram-positive bacteria
      of the order Actinomycetales (Netzer et al., J Bacteriol 192:5688-5699, 2010).
      The characteristic yellow phenotype of C. glutamicum is due to the cyclic C50
      carotenoid decaprenoxanthin and its glycosides. Decaprenoxanthin production has
      been improved by plasmid-borne overexpression of endogenous genes of
      carotenogenesis. Gene deletion resulted in the production of the C40 carotenoid
      lycopene, an intermediate of decaprenoxanthin biosynthesis. Heterologous gene
      expression was required to develop strains overproducing nonnative carotenoids
      and terpenes, such as astaxanthin (Henke et al., Mar Drugs 14:E124, 2016) and (+)
      valencene (Frohwitter et al., J Biotechnol 191:205-213, 2014). Integration of
      additional copies of endogenous genes expressed from strong promoters improved
      isoprenoid biosynthesis. Here, we describe C. glutamicum strains, plasmids, and
      methods for overexpression of endogenous and heterologous genes, gene deletion,
      replacement, and genomic integration. Moreover, strain cultivation as well as
      extraction, identification, and quantitative determination of terpenes and
      carotenoids produced by C. glutamicum is detailed.

PMID- 30109630
TI  - Rapid and Selective Screening Method for Isolation and Identification of
      Carotenoid-Producing Bacteria.
AB  - Carotenoids are naturally occurring yellow to red pigments with many biological
      activities including antioxidant, anticancer, anti-inflammatory, membrane
      stabilizers, and precursors for vitamin A. These biological activities are linked
      with many health benefits (e.g., anticarcinogenic activity, prevention of chronic
      diseases, etc.), which grew the interest of several industrial sectors especially
      in food, feed, nutraceuticals, cosmetics, and pharmaceutical industries. The
      production of natural carotenoids from microbial sources such as bacteria can
      help meet the growing global market of carotenoids estimated at $1.5 billion in
      2014 and is expected to reach 1.8 billion in 2019. This chapter demonstrates,
      step-by-step, the development of a rapid and selective screening method for
      isolation and identification of carotenoid-producing microorganisms and their
      carotenoid analysis. This method involves three main procedures: UV treatment,
      sequencing analysis of 16S rRNA genes, and carotenoids analysis using rapid and
      effective HPLC-diode array-MS methods.

PMID- 30109631
TI  - Purification and Identification of Astaxanthin and Its Novel Derivative Produced
      by Radio-tolerant Sphingomonas astaxanthinifaciens.
AB  - The red diketocarotenoid, astaxanthin, exhibits extraordinary health-promoting
      activities such as antioxidant, anti-inflammatory, antitumor, and immune booster,
      which may potentially protect against many degenerative diseases such as cancers,
      heart diseases, and exercise-induced fatigue. These numerous health benefits and
      consumer interest in natural products have therefore increased the market demand
      of astaxanthin as a nutraceutical and medicinal ingredient in food, aquaculture
      feed, and pharmaceutical industries. Consequently, many research efforts have
      been made to discover novel microbial sources with effective biotechnological
      production of astaxanthin. Using a rapid screening method based on 16S rRNA gene,
      and effective HPLC-Diode array-MS methods for carotenoids analysis, we isolated a
      novel astaxanthin-producing bacterium (strain TDMA-17T) that belongs to the
      family Sphingomonadaceae (Asker et al., FEMS Microbiol Lett 273:140-148, 2007).In
      this chapter, we provide a comprehensive description of the methods used for the
      analysis and identification of carotenoids produced by strain TDMA-17T. We will
      also describe the methods of isolation and identification for a novel bacterial
      carotenoid (an astaxanthin derivative), a major carotenoid that is produced by
      the novel strain. Finally, the identification methods of the novel strain will be
      summarized.

PMID- 30109632
TI  - Screening, Isolation, and Identification of Zeaxanthin-Producing Bacteria.
AB  - Zeaxanthin is a yellow xanthophyll, dihydroxy-carotenoid, that is naturally found
      in some of the green, orange, and yellow vegetables and fruits and has a powerful
      antioxidant activity. Epidemiological evidences suggest that increasing the
      consumption of zeaxanthin in the diet is associated with a lower risk of age
      related macular degeneration (ARMD) and cataracts, two of the leading causes of
      blindness in the world. Zeaxanthin is a promising nutraceutical/colorant with
      many applications in feed, food, and pharmaceutical industries. Currently, the
      commercial production of zeaxanthin is dependent on synthetic routes with
      limitation in production from biological sources. However, the biotechnological
      production of natural zeaxanthin is favored due to its safety, potential large
      scale production and consumers' preference for natural additives. In this
      chapter, we describe a rapid screening method based on 16S rRNA gene sequencing
      and effective HPLC with diode array detector/MS methods for the isolation and
      identification of zeaxanthin-producing bacteria and their carotenoid analysis.

PMID- 30109633
TI  - Synthesis of Carotenoids of Industrial Interest in the Photosynthetic Bacterium
      Rhodopseudomonas palustris : Bioengineering and Growth Conditions.
AB  - Rhodopseudomonas palustris is a purple photosynthetic bacterium that accumulates
      in the inner membrane the photosynthetic pigment spirilloxanthin, formed from
      lycopene. Here, we describe the procedures used to successfully engineer Rps.
      palustris strains to reroute the production of lycopene toward the synthesis of
      beta-carotene or canthaxanthin. The crtCD genes specifically involved in
      spirilloxanthin were replaced by crtY and crtW genes from Bradyrhizobium ORS278
      to synthesize beta-carotene and (or) canthaxanthin, two pigments of industrial
      interest. Since the synthesis of canthaxanthin depends on the presence of oxygen,
      the procedure to optimize their production is also proposed. By modulating the
      light and oxygen during the growth process, a single species of photosynthetic
      bacteria, with an efficient growth rate, produces various carotenoids of
      economical interest.

PMID- 30109634
TI  - Molecular Tools for Carotenogenesis Analysis in the Mucoral Mucor circinelloides.
AB  - The carotene producer Mucor circinelloides is the fungus within the Mucoromycota
      phylum with the widest repertoire of molecular tools to manipulate its genome.
      The initial development of an effective procedure for genetic transformation and
      later improvements have resulted in an expansion of available tools, which
      include gene replacement, inactivation of gene expression by RNA silencing, gene
      overexpression, and functional genomics. Moreover, sequencing of its genome has
      given a definitive boost to these techniques making attainable the study of genes
      involved in many physiological or developmental processes, including carotenoid
      biosynthesis. Here, we describe in detail the latest molecular techniques
      currently used in M. circinelloides that have made it a valuable model for
      studying gene function within its phylum.

PMID- 30109635
TI  - Expression Vectors and Gene Fusions for the Directed Modification of the
      Carotenoid Biosynthesis Pathway in Mucor circinelloides.
AB  - Several fungal species, particularly some included in the Mucoromycotina, have
      been used to develop fermentation processes for the production of beta-carotene.
      Oxygenated derivatives of beta-carotene (xanthophylls) are desirable value-added
      products, and the preference by the market of carotenoids from biological sources
      has increased the research in different carotenoid-producing organisms. We
      currently use Mucor circinelloides f. lusitanicus as a model organism to develop
      strains with an increased content of new and more valuable carotenoids. The main
      carotenoid accumulated by M. circinelloides is beta-carotene, although it has
      some hydroxylase activity and produces low amounts of zeaxanthin. On the other
      hand, in astaxanthin-producing organisms two enzymatic activities are required
      for the production of astaxanthin from beta-carotene: a hydroxylase and a
      ketolase. In this chapter, we delineate part of our efforts to construct
      genetically modified strains that could advance in the improvement of carotenoid
      accumulation by this fungus and the diversification of its carotenoid content.
      Accordingly, we describe detailed and empirically tested protocols for the
      construction of functional expression vectors and gene fusions.

PMID- 30109636
TI  - Lycopene Production by Mated Fermentation of Blakeslea trispora.
AB  - Lycopene is a carotenoid mainly present in red-colored fruits and vegetables. Its
      value in the pharmaceutical and food industry is linked to its benefits for the
      human health, including properties against cancer and cardiovascular diseases,
      and its use as a food colorant. Lycopene can be produced either by synthetic or
      natural means, but there is a preference for the second, since it is considered a
      more eco-friendly and less harmful process. Among natural methods for obtaining
      lycopene, microbial fermentation is a good alternative to extraction from plants
      that naturally contain lycopene, since it implies obtaining higher and more
      specific amounts of this carotenoid. This chapter describes lycopene production
      by fermentation of the fungus Blakeslea trispora, a naturally carotenoid
      producer, at 30 L scale. This procedure involves separated growth of the two
      sexual mating types of B. trispora during the vegetative stages and the use of a
      lycopene cyclase inhibitor to achieve lycopene accumulation during the production
      stage.

PMID- 30109637
TI  - HPLC Analysis of Carotenoids in Neurosporaxanthin-Producing Fungi.
AB  - The ascomycetous fungi Fusarium fujikuroi and Neurospora crassa are widely used
      as research models in the study of secondary metabolism and photobiology,
      respectively. Both fungi exhibit a similar carotenoid pathway, for which all the
      genes and enzymes have been identified. Under standard laboratory conditions,
      either F. fujikuroi or N. crassa accumulate a mixture of neurosporaxanthin, a
      carboxylic apocarotenoid acid, and several of its carotene precursors. We
      formerly described methods for the identification and quantification of
      neurosporaxanthin. However, the differences in polarity between this acidic
      xanthophyll and neutral carotenes make their global analysis cumbersome. Here we
      propose a simple HPLC methodology for the efficient separation of
      neurosporaxanthin and earlier pathway intermediates in a single HPLC run. This
      method should be useful to check the abundance of neurosporaxanthin under
      different experimental conditions and to evaluate the relative proportions of
      their different carotene precursors. To assess the validity of the method, we
      have compared the carotenoid profiles in samples of mycelia of F. fujikuroi and
      conidia of N. crassa, in both cases obtained from surface cultures of a wild
      strain of each species.

PMID- 30109638
TI  - Extraction and Analysis of Carotenes and Xanthophylls Produced by
      Xanthophyllomyces dendrorhous.
AB  - Xanthophyllomyces dendrorhous, a heterobasidiomycetous yeast that represents the
      teleomorphic state of Phaffia rhodozyma, is used as a natural source of several
      carotenoids, such as the xanthophyll astaxanthin. Here, we describe the culture
      procedure for the production of carotenoids in X. dendrorhous and a simple and
      rapid analytical method for the optimized extraction and HPLC determination of
      intracellular beta-carotene, astaxanthin, canthaxanthin, and zeaxanthin.

PMID- 30109639
TI  - Isolation and Selection of New Astaxanthin-Producing Strains of Phaffia
      rhodozyma.
AB  - Astaxanthin is a xanthophyll pigment of high economic value for its use as a
      feeding component in aquaculture. Phaffia rhodozyma (Xanthophyllomyces
      dendrorhous) is a basidiomycetous fungi able to synthesize astaxanthin as its
      major carotenoid, the only known yeast species bearing the capability to produce
      this type of carotenoid and the only tremellomycetes with biotechnological
      application. Recently, the habitat and intraspecific variability of this species
      have been found to be wider than previously expected, encouraging the search for
      new wild strains with potential biotechnological applications. Here we describe
      effective procedures for isolation of P. rhodozyma from environmental samples,
      accurate identification of the strains, analysis of their astaxanthin content,
      and proper conservation of the isolates.

PMID- 30109640
TI  - Engineering Pichia pastoris for the Production of Carotenoids.
AB  - Carotenoids are one of the most diverse and widely distributed classes of
      pigments in the biosphere and exhibit a variety of functions in the nature. Their
      importance and biotechnological applications are higher and higher, but their
      sources are not increasing in the same exponential way. Here we describe the
      process of bioengineering the yeast Pichia pastoris by sequential transformation
      to get an astaxanthin producer.

PMID- 30109641
TI  - Isolation and Characterization of Extrachromosomal Double-Stranded RNA Elements
      from Carotenogenic Yeasts.
AB  - Double-stranded RNA (dsRNA) molecules are widely found in yeasts and filamentous
      fungi. It has been suggested that these molecules may play an important role in
      the evolution of eukaryote genomes and could be a valuable tool in yeast typing.
      The characterization of these extrachromosomal genetic elements is usually a
      laborious process, especially when trying to analyze a large number of samples.
      In this chapter, we describe a simple method to isolate dsRNA elements from
      yeasts using low amounts of starting material and their application to different
      Xanthophyllomyces dendrorhous strains and other psychrotolerant carotenogenic
      yeasts. Furthermore, the methodologies for enzymatic and hybridization
      characterizations and quantification of relative dsRNA abundance are detailed.

PMID- 30109642
TI  - Cannabinoid-Based Therapies and Brain Development: Potential Harmful Effect of
      Early Modulation of the Endocannabinoid System.
AB  - The endocannabinoid retrograde signaling pathway is widely expressed in the
      central nervous system, where it plays major roles in regulating synaptic
      plasticity (excitatory and inhibitory) through long-term potentiation and long
      term depression. The endocannabinoid system (ECS) components-cannabinoid
      receptors, endocannabinoids and synthesis/degradation enzymes-are expressed and
      are functional from early developmental stages and throughout adolescent cortical
      development, regulating progenitor cell fate, neural differentiation, migration
      and survival. This may potentially confer increased vulnerability to adverse
      outcomes from early cannabinoid exposure. Cannabidiol (CBD) is one of the most
      studied exogenous cannabinoids, and CBD-enriched Cannabis extracts have been
      widely (and successfully) used as adjuvants to treat children with refractory
      epilepsy, and there is even a Food and Drug Administration (FDA)-approved drug
      with purified CBD derived from Cannabis. However, there is insufficient
      information on possible long-term changes in the central nervous system caused by
      cannabinoid treatments during early childhood. Like the majority of cannabinoids,
      CBD is able to exert its effects directly and indirectly through the ECS, which
      can perturb the regulatory processes mediated by this system. In addition, CBD
      has a large number of non-endocannabinoid targets, which can explain CBD's
      effects. Here, we review the current knowledge about CBD-based therapies-pure and
      CBD-enriched Cannabis extracts-in studies with pediatric patients, their side
      effects, and their mechanisms of action regarding the central nervous system and
      neurodevelopment aspects. Since Cannabis extracts contain Delta9
      tetrahydrocannabinol (Delta9-THC), we consider that pure CBD is possibly safer
      for young patients. Nevertheless, CBD, as well as other natural and/or synthetic
      cannabinoids, should be studied in more detail as a therapeutic alternative to
      CBD-enriched Cannabis extracts for young patients.

PMID- 30109644
TI  - Lipases: An Overview.
AB  - Lipases are ubiquitous enzymes, widespread in nature. They were first isolated
      from bacteria in the early nineteenth century, and the associated research
      continuously increased due to the characteristics of these enzymes. This chapter
      reviews the main sources, structural properties, and industrial applications of
      these highly studied enzymes.

PMID- 30109646
TI  - Phospholipases: An Overview.
AB  - Phospholipases are lipolytic enzymes that hydrolyze phospholipid substrates at
      specific ester bonds. Phospholipases are widespread in nature and play very
      diverse roles from aggression in snake venom to signal transduction, lipid
      mediator production, and metabolite digestion in humans. Phospholipases vary
      considerably in structure, function, regulation, and mode of action. Tremendous
      advances in understanding the structure and function of phospholipases have
      occurred in the last decades. This introductory chapter is aimed at providing a
      general framework of the current understanding of phospholipases and a discussion
      of their mechanisms of action and emerging biological functions.

PMID- 30109643
TI  - Rare single gene disorders: estimating baseline prevalence and outcomes
      worldwide.
AB  - As child mortality rates overall are decreasing, non-communicable conditions,
      such as genetic disorders, constitute an increasing proportion of child
      mortality, morbidity and disability. To date, policy and public health programmes
      have focused on common genetic disorders. Rare single gene disorders are an
      important source of morbidity and premature mortality for affected families. When
      considered collectively, they account for an important public health burden,
      which is frequently under-recognised. To document the collective frequency and
      health burden of rare single gene disorders, it is necessary to aggregate them
      into large manageable groupings and take account of their family implications,
      effective interventions and service needs. Here, we present an approach to
      estimate the burden of these conditions up to 5 years of age in settings without
      empirical data. This approaches uses population-level demographic data, combined
      with assumptions based on empirical data from settings with data available, to
      provide population-level estimates which programmes and policy-makers when
      planning services can use.

PMID- 30109645
TI  - Carbohydrate Esterases: An Overview.
AB  - Carbohydrate esterases are a group of enzymes which release acyl or alkyl groups
      attached by ester linkage to carbohydrates. The CAZy database, which classifies
      enzymes that assemble, modify, and break down carbohydrates and glycoconjugates,
      classifies all carbohydrate esterases into 16 families. This chapter is an
      overview of the research for nearly 50 years around the main groups of
      carbohydrate esterases dealing with the degradation of polysaccharides, their
      main biochemical and molecular traits, as well as its application for the
      synthesis of high added value esters.

PMID- 30109647
TI  - Functional-Based Screening Methods for Detecting Esterase and Lipase Activity
      Against Multiple Substrates.
AB  - Functional screens have been extensively used for searching native enzymes or
      mutant variants in clone libraries. Esterases and lipases are the most retrieved
      enzymes, because they are within the more demanded industrial enzymes and because
      a number of simple and generic screening methods can be applied for their screen.
      Here, we describe the use of a generic pH indicator assay protocol which
      unambiguously allows detecting in high-throughput manner esterase and lipase
      activity and quantifying specific activities using an ester concentration above
      0.5 mM. The described method is simple and generic to allow the selection of
      esterases and lipases targeting desired esters.

PMID- 30109648
TI  - A Continuous and Sensitive Spectrophotometric Assay for Lipase and Phospholipase
      A Activities Using alpha-Eleostearic Acid-Containing Substrates.
AB  - To date, several sensitive methods, based on radiolabeled elements or sterically
      hindered fluorochrome groups, are usually employed to screen lipase and
      phospholipase A (PLA) activities. Here, a new ultraviolet spectrophotometric
      assay for lipase or PLA was developed using natural triglycerides or synthetic
      glycerophosphatidylcholines containing alpha-eleostearic acid (9Z, 11E, 13E
      octadecatrienoic acid) purified from Aleurites fordii seed oil. The conjugated
      triene present in alpha-eleostearic acid constitutes an intrinsic chromophore and
      consequently confers strong UV absorption properties of this free fatty acid as
      well as of lipid substrates harboring it. The substrate was coated into the wells
      of a microplate, and the lipolytic activities were measured by the absorbance
      increase at 272 nm due to the transition of alpha-eleostearic acid moiety from
      the adsorbed to the soluble state. This continuous assay is compatible with a
      high-throughput screening method and can be applied specifically to the screening
      of new potential lipase, PLA1 and PLA2 inhibitors.

PMID- 30109649
TI  - Direct and Continuous Measurement of Phospholipase D Activities Using the
      Chelation-Enhanced Fluorescence Property of 8-Hydroxyquinoline.
AB  - Phospholipase D (PLD) hydrolyzes phospholipids to form phosphatidic acid (PA) and
      the corresponding headgroup. To date, PLD has been linked to several pathologies,
      such as cancer, making this enzyme an important therapeutic target. However, most
      PLD assays developed so far are either discontinuous or based on the indirect
      determination of choline released upon phosphatidylcholine (PC) hydrolysis.
      Therefore, we designed a PLD assay that is based on the chelation-enhanced
      fluorescence property of 8-hydroxyquinoline. This assay exhibits a strong
      fluorescence signal upon Ca2+ complexation with the PLD-generated PA and is not
      limited to PC as the substrate but allows the use of natural phospholipids with
      various headgroups. Besides, this easy-to-handle assay allows to monitor
      prokaryotic and eukaryotic PLD activities in a continuous way and on a microplate
      scale.

PMID- 30109650
TI  - Lipase and Phospholipase Activity Methods for Marine Organisms.
AB  - Lipases are very important enzymes having a role in fat digestion and lipid
      metabolism in marine animals, plants, and microorganisms. The methods for
      measuring lipase and phospholipase activity have been applied in several studies;
      however, considering that lipases are water-soluble molecules and their
      substrates are generally water-insoluble molecules, several steps are required
      for measuring their digestion products. After a general review of the main type
      of methods used in marine lipase studies, and experimental procedures, a proposal
      of new or improved methods is described in order to facilitate the lipase
      activity measurements in marine organisms.

PMID- 30109651
TI  - Functional Expression of Plant Lipases: The Case of CpLip1 from Carica papaya.
AB  - Carica papaya latex is one of the most studied sources of plant lipases. However,
      the complexity of the matrix composition makes it difficult to isolate and purify
      the lipolytic enzymes present in Carica papaya latex. Therefore, diverse
      strategies have been developed to study the catalytic properties of these
      enzymes.Recently the first lipase from Carica papaya latex (CpLip1) has been
      successfully cloned and expressed in order to study their catalytic properties.
      In order to improve the catalytic properties and increase the potential for its
      use at industrial scale.In this chapter, a practical protocol to recombinant
      CpLip1 lipase is given.

PMID- 30109652
TI  - Heterologous Expression and Functional Characterization of Sparidae Fish
      Digestive Phospholipase A2.
AB  - In this study, we have produced for the first time a fish phospholipase (PLA2) in
      heterologous system (E. coli). The Diplodus annularis PLA2 (DaPLA2) was then
      refolded from inclusion bodies and purified by Ni-affinity chromatography. We
      used the pH-stat method (with emulsified phosphatidylcholine as substrate) and
      the monomolecular film technique (using various glycerophospholipids substrates
      spread in the form of monomolecular films at the air-water interface) to access
      the biochemical and kinetic properties of the recombinant DaPLA2. The DaPLA2 was
      found to be active and stable at higher temperatures (37-50  degrees C) than
      expected. Interestingly, DaPLA2 hydrolyzes efficiently both purified
      phosphatidylglycerol and phosphatidylethanolamine at 20 mN/m. These analytical
      results corroborate with the fact that the catalytic activity of DaPLA2, measured
      with the pH-stat using egg yolk as substrate, is mainly due to the hydrolysis of
      the PE fraction present in egg yolk, whereas the phosphatidylglycerol is a
      hallmark substrate for the most secreted PLA2-IB.

PMID- 30109653
TI  - Expression and Purification of Recombinant Vigna unguiculata Phospholipase D in
      Pichia pastoris for Structural Studies.
AB  - The production of pure enzymes in high quantities is a proven strategy to study
      the catalytic mechanism as well as the solving of structure at the atomic scale
      for therapeutic or industrial purposes. Phospholipase D (PLD, EC 3.1.4.4) is
      found in a wide majority of living organisms and has been shown to be involved in
      signal transduction, vesicle trafficking, and membrane metabolism processes.
      Located at the membrane-cytoplasm interface, plant PLDs are soluble but also bear
      an evident hydrophobic aspect making challenging its expression and its
      purification in large quantity. So far there is no high-resolution three
      dimensional structure for a eukaryotic PLD. The protocols herein describe the
      cloning of the eukaryotic recombinant PLDalpha of Vigna unguiculata (cowpea) into
      the yeast expression system Pichia pastoris and its two-step purification
      process. This allowed us to purify to homogeneity hundreds of micrograms of
      highly pure protein to conduct in fine structural studies.

PMID- 30109654
TI  - Recent Advances in Pichia pastoris as Host for Heterologous Expression System for
      Lipases: A Review.
AB  - The production of heterologous lipases is one of the most promising strategies to
      increase the productivity of the bioprocesses and to reduce costs, with the final
      objective that more industrial lipase applications could be implemented.In this
      chapter, an overview of the new success in synthetic biology, with traditional
      molecular genetic techniques and bioprocess engineering in the last 5 years in
      the cell factory Pichia pastoris, the most promising host system for heterologous
      lipase production, is presented.The goals get on heterologous Candida antarctica,
      Rhizopus oryzae, and Candida rugosa lipases, three of the most common lipases
      used in biocatalysis, are showed. Finally, new cell factories producing
      heterologous lipases are presented.

PMID- 30109655
TI  - Solid-State Fermentation as an Economic Production Method of Lipases.
AB  - Solid-state fermentation (SSF) has been largely employed during the last three
      decades to produce different biomolecules of industrial interest, particularly
      enzymes. Through the use of agroindustrial wastes as SSF substrates, an economic
      process of lipases production can be achieved. In this chapter we describe a
      comprehensive SSF method for producing an economical preparation of Rhizomucor
      miehei lipase, employing sugarcane bagasse and used vegetal oil as substrates. To
      demonstrate the usefulness of the lipase produced by this method, we utilized
      directly the dried fermented solid, as a heterogeneous biocatalyst for the
      ethanolysis of different fats and oils. Final ethyl ester conversions (>90%, 24
      h) were similar with those obtained using a commercial immobilized Rhizomucor
      miehei lipase at our best conditions. In this work we demonstrated that SSF is an
      easy and economical method for the production of lipases that can be used
      directly as heterogeneous biocatalysts for biodiesel production, employing low
      cost feedstocks.

PMID- 30109656
TI  - Synthetic Biology to Improve the Production of Lipases and Esterases (Review).
AB  - Synthetic biology is an emergent field of research whose aim is to make biology
      an engineering discipline, thus permitting to design, control, and standardize
      biological processes. Synthetic biology is therefore expected to boost the
      development of biotechnological processes such as protein production and enzyme
      engineering, which can be significantly relevant for lipases and esterases.

PMID- 30109657
TI  - Rational Design Strategy as a Novel Immobilization Methodology Applied to Lipases
      and Phospholipases.
AB  - Immobilization of lipases and phospholipases, mainly on water-insoluble carriers,
      helps in their economic reusing and in the development of continuous
      bioprocesses. Design of efficient lipase and phospholipase-immobilized systems is
      rather a difficult task. A lot of research work has been done in order to
      optimize immobilization techniques and procedures and to develop efficient
      immobilized systems. We conceived a new strategy for the rational design of
      immobilized derivatives (RDID) in favor of the successful synthesis of optimal
      lipase and phospholipase-immobilized derivatives, aiming the prediction of the
      immobilized derivative's functionality and the optimization of load studies. The
      RDID strategy begins with the knowledge of structural and functional features of
      synthesis components (protein and carrier) and the practical goal of the
      immobilized product. The RDID strategy was implemented in a software named
      RDID1.0. The employment of RDID allows selecting the most appropriate way to
      prepare immobilized derivatives more efficient in enzymatic bioconversion
      processes and racemic mixture resolution.

PMID- 30109658
TI  - Lipase-Catalyzed Synthesis of Fatty Acid Esters of Trisaccharides.
AB  - Carbohydrate fatty acid esters have a broad spectrum of applications in the food,
      cosmetic, and pharmaceutical industries. The enzyme-catalyzed acylation is
      significantly more selective than the chemical process and is carried out at
      milder conditions. Compared with mono- and disaccharides, the acylation of
      trisaccharides has been less studied. However, trisaccharide esters display
      notable bioactive properties, probably due to the higher hydrophilicity of the
      sugar head group. In this chapter, we describe the acylation of two
      trisaccharides, maltotriose and 1-kestose, catalyzed by different immobilized
      lipases, using vinyl esters as acyl donors. To illustrate the potential of such
      compounds, the antitumor activity of 6"-O-palmitoyl-maltotriose is shown.

PMID- 30109659
TI  - Targeting Phospholipase D Genetically and Pharmacologically for Studying
      Leukocyte Function.
AB  - Phospholipase D (PLD), is a protein that breaks down phospholipids, maintaining
      structural integrity and remodeling of cellular or intracellular membranes, as
      well as mediating protein trafficking and cytoskeletal dynamics during cell
      motility. One of the reaction products of PLD action is phosphatidic acid (PA).
      PA is a mitogen involved in a large variety of physiological cellular functions,
      such as cell growth, cell cycle progression, and cell motility. We have chosen as
      cell models the leukocyte polymorphonuclear neutrophil and the macrophage as
      examples of cell motility. We provide a three-part method for targeting PLD
      genetically and pharmacologically to study its role in cell migration. In the
      first part, we begin with genetically deficient mice PLD1-KO and PLD2-KO. We
      describe bone marrow neutrophil (BMN) isolation; BMN is labeled fluorescently and
      can be used for studying tissue-damaging neutrophilia in ischemia-reperfusion
      injury (IRI). In the second part, we begin also with PLD1-KO and PLD2-KO and
      prepare bone marrow-derived macrophages (BMDM), first from monocytes and then
      inducing macrophage differentiation in culture with continuous incubation of
      cytokines. We use BMDM to find experimentally if PLD woul play a role in
      cholesterol phagocytosis, which is the first step in atherosclerosis progression.
      In the third part, we study PLD function in BMN and BMDM with PLD enzyme
      pharmacological inhibitors instead of genetically deficient mice, to ascertain
      the particular contributions of isoforms PLD1 and PLD2 on leukocyte function. By
      using the three-step thorough approach, we could understand the molecular
      underpinning of PLD in the pathological conditions indicated above, IRI
      neutrophilia and atherosclerosis.

PMID- 30109660
TI  - Lipase-Catalyzed Synthesis of Structured Lipids at Laboratory Scale.
AB  - In this chapter, some examples of laboratory protocols to produce functional
      structured lipids, namely, human milk fat substitutes, dietetic triacylglycerols,
      and interesterified fat blends with improved nutritional and rheological
      properties, catalyzed either by immobilized commercial or noncommercial lipase
      preparations, are presented. In addition to batch synthesis, the continuous
      production in packed- or fluidized-bed bioreactors is addressed, as well as the
      evaluation of operational stability of the biocatalysts used (either in batch
      reuses or in continuous mode).

PMID- 30109661
TI  - Lipase-Catalyzed Acetylation and Esterification of Bile Acids.
AB  - In this chapter we describe the application of lipases as catalysts in reactions
      on a relevant family of steroids: the bile acids. Twenty three monoacetyl,
      diacetyl, and ester derivatives of deoxycholic, chenodeoxycholic, lithocholic,
      and cholic acids, 15 of them new compounds, were obtained through lipase
      catalyzed acetylation, esterification, and alcoholysis reactions in very good to
      excellent yield and a highly regioselective way. Among them, acetylated ester
      products, in which the lipase catalyzed both reactions in one pot, were obtained.
      The influence of various reaction parameters in the enzymatic reactions, such as
      enzyme source, nucleophile/substrate ratio, enzyme/substrate ratio, solvent, and
      temperature, was studied. Some of the reported products are novel, and it is not
      possible to obtain them satisfactorily by following traditional synthetic
      procedures. Due to its singular structure containing three hydroxyl groups,
      cholic acid showed a different behavior in the enzymatic reactions, from that
      observed for the other three bile acids studied. In order to shed light to
      different behaviors of bile acids in the enzymatic reactions, molecular modeling
      was applied to substrates and some derivatives.

PMID- 30109662
TI  - Lipases in Green Chemistry: Deep Eutectic Solvents (DES) as New Green Solvents.
AB  - Deep eutectic solvents (DES) may become important alternatives as versatile,
      biodegradable, and cost-effective solvents for biocatalysis. Especially for
      reactions where substrates and products of different polarities are combined, the
      design of a tailored solvent that may dissolve all compounds-while being enzyme
      compatible at the same time-appears to be a strong ally in sustainable chemistry.
      Herein it is shown that the combination of DES with "water as cosolvent" (in a
      range from 5% to 20% water, v/v) leads to non-conventional solvents with
      significantly reduced viscosity. In these media, lipases and proteases can
      perform synthetic reactions efficiently, and hydrolytic side reactions remain
      suppressed (even at 20% water, v/v). The use of these less viscous non
      conventional media could also provide options for hydrolase-catalyzed synthetic
      reactions even in continuous fashion.

PMID- 30109663
TI  - Chemoenzymatic Synthesis of Nitrogen Polymers with Biomedical Applications
      Catalyzed by Lipases.
AB  - The application of Candida antarctica lipase B as catalyst in the synthesis of
      two examples of nitrogen polymers is described. Firstly, we report a novel linear
      polyamidoamine oligomer, obtained by polymerization of ethyl acrylate and N
      methyl-1,3-diaminopropane, catalyzed by Candida antarctica lipase B immobilized
      on polypropylene. The second part of the chapter describes an efficient route for
      the synthesis of a novel beta-peptoid oligomer with hydroxyalkyl pendant groups
      in the nitrogen atom, through the polymerization of ethyl N-(2-hydroxyethyl)-beta
      alaninate catalyzed by Candida antarctica lipase B physically adsorbed within a
      macroporous poly(methyl methacrylate-co-butyl methacrylate) resin. Moreover, two
      derivatives of the beta-peptoid oligomer were prepared: by acetylation and by
      grafting polycaprolactone. This last process was performed through ring-opening
      polymerization of caprolactone from the beta-peptoid pendant hydroxyl groups and
      afforded a brush copolymer. The products were blended with polycaprolactone to
      make films by solvent casting. The inclusion of the acyl derivatives of the beta
      peptoid to polycaprolactone affected the morphology of the film yielding micro-
      and nanostructured patterns. The obtained products showed biomedical
      applications.

PMID- 30109664
TI  - Lipases as Biocatalyst for Biodiesel Production.
AB  - Global shortages of fossil fuels, significant rise in the price of crude oil, and
      increased environmental concerns have stimulated the rapid growth of biodiesel
      production. Biodiesel is generally produced through transesterification reaction
      catalyzed either chemically or enzymatically. Enzymatic transesterification is of
      interest since it shows advantages over the chemical process and, in addition, is
      considered a "green" process. This chapter reviews the current status of
      biodiesel production with a lipase biocatalysis approach, including sources of
      lipases, kinetics, lipase immobilization techniques, and lipase reaction
      mechanism for biodiesel production. Factors affecting biodiesel production and
      the economic feasibility of lipase biodiesel production are also covered.

PMID- 30109665
TI  - Lipase, Phospholipase, and Esterase Biosensors (Review).
AB  - A biosensor is a device composed by a biological recognition element and a
      transducer that delivers selective information about a specific analyte.
      Technological and scientific advances in the area of biology, bioengineering,
      catalysts, electrochemistry, nanomaterials, microelectronics, and microfluidics
      have improved the design and performance of better biosensors. Enzymatic
      biosensors based on lipases, esterases, and phospholipases are valuable
      analytical apparatus which have been applied in food industry, oleochemical
      industry, biodegradable polymers, environmental science, and overall the medical
      area as diagnostic tools to detect cholesterol and triglyceride levels in blood
      samples. This chapter reviews recent developments and applications of lipase-,
      esterase-, and phospholipase-based biosensors.

PMID- 30109666
TI  - The Reduction of Visceral Adipose Tissue after Roux-en-Y Gastric Bypass Is more
      Pronounced in Patients with Impaired Glucose Metabolism.
AB  - PURPOSE: Visceral adipose tissue (VAT) is associated with cardiometabolic risk
      factors and insulin resistance. The physiological mechanisms underlying the
      benefits of Roux-en-Y gastric bypass surgery (RYGB) on glucose metabolism remain
      incompletely understood. The impact of RYGB on VAT was assessed among three
      groups of patients stratified by their glucose tolerance before surgery. METHODS:
      Forty-four obese women were categorized into normoglycemia (n = 21), impaired
      glucose tolerance (IGT, n = 18) and diabetes (n = 5) before surgery. Body
      composition measured by dual-energy X-ray absorptiometry (DXA) was performed
      before surgery, 6 months and 12 months after. RESULTS: The three groups had
      comparable mean age (mean 38.6 +/- SD 9.9) and BMI at baseline (41.9 +/- 4.3
      kg/m2). After 12 months, total weight loss (mean 35.1% +/- 7.5) and excess weight
      loss (91.1% +/- 25.1) were similar between groups. Pre-surgery mean VAT was
      significantly higher in diabetes (mean 2495 +/- 616 g) than in normoglycemia
      (1750 +/- 617 g, p = 0.02). The percentage of VAT to total body fat was
      significantly higher in diabetes (mean 4.4% +/- 0.9) compared to normoglycemia
      (2.9% +/- 0.8, p = 0.003). Twelve months after surgery, VAT loss was
      significantly greater among patients with diabetes (mean 1927 +/- 413 g) compared
      to normoglycemia (1202 +/- 450, p = 0.009). CONCLUSIONS: RYGB leads to important
      VAT loss, and this loss is greater in patients with diabetes prior to surgery. As
      VAT is associated with insulin resistance, this reduction may account for the
      profound impact of this surgery on glucose metabolism.

PMID- 30109668
TI  - Postoperative Care Fragmentation Is Associated with Increased 30-Day Mortality
      after Bariatric Surgery.
AB  - BACKGROUND: Compromised access following bariatric centers-or-excellence
      designations may have led to increased incidence of non-index readmissions and
      worsened care fragmentation. We seek to evaluate risk factors and impact of non
      index readmissions on short-term mortality during readmission using a national
      bariatric registry data from 2015. METHODS: A retrospective cohort study was
      performed using a national clinical database. Multivariate logistic regression
      models were developed to quantify association between non-index readmissions and
      30-day mortality among bariatric patients with 30-day readmissions. RESULTS: A
      total of 4704 patients were identified as undergoing bariatric surgery and
      readmitted within 30 days. Of these, 325 (6.9%) patients were readmitted to a non
      index facility while the rest were hospitalized at the original hospital. Patient
      characteristics were largely similar between the two comparison groups, although
      patients with in-hospital complications and non-home disposition during the
      initial stay were more likely to experience non-index readmissions. Multivariate
      regression demonstrated that non-index readmission was associated with an
      adjusted odds ratio of 4.4 for 30-day mortality (95% confidence interval 2.6-9.2,
      p < 0.01). The most common reason for mortality for both index and non-index
      readmissions was pulmonary embolism. CONCLUSIONS: Care fragmentation may lead to
      increased 30-day mortality during readmissions following bariatric surgery.
      Heightened vigilance and longitudinal follow-up planning is recommended for
      patients with elevated risk for venous thromboembolism.

PMID- 30109667
TI  - Bariatric Surgery in Patients with Cirrhosis and Portal Hypertension.
AB  - INTRODUCTION: Studies on bariatric patients with cirrhosis and portal
      hypertension are limited. The aim of this study was to review our experience in
      cirrhotic patients with portal hypertension who had bariatric surgery. METHOD:
      All cirrhotic patients with portal hypertension who underwent laparoscopic
      bariatric surgery, from 2007 to 2017, were retrospectively reviewed. RESULTS:
      Thirteen patients were included; eight (62%) were female. The median age was 54
      years (interquartile range, IQR 49-60) and median BMI was 48 kg/m2 (IQR 43-55).
      Portal hypertension was diagnosed based on endoscopy (n = 5), imaging studies (n
      = 3), intraoperative increased collateral circulation (n = 2), and endoscopy and
      imaging studies (n = 3). The bariatric procedures included sleeve gastrectomy (n
      = 10, 77%) and Roux-en-Y gastric bypass (n = 3, 23%). The median length of
      hospital stay was 3 days (IQR 2-4). Three 30-day complications occurred including
      wound infection (n = 1), intra-abdominal hematoma (n = 1), and subcutaneous
      hematoma (n = 1). No intraoperative or 30-day mortalities. There were 11 patients
      (85%) at 1-year follow-up and 9 patients (69%) at 2-year follow-up. At 2 years,
      the median percentage of excess weight loss (EWL) and total weight loss (TWL)
      were 49 and 25%, respectively. There was significant improvement in diabetes
      (100%), dyslipidemia (100%), and hypertension (50%) at 2 years after surgery.
      CONCLUSION: Bariatric surgery in selected cirrhotic patients with portal
      hypertension is relatively safe and effective.

PMID- 30109669
TI  - Effects of Two Preoperatory Weight Loss Diets on Hepatic Volume, Metabolic
      Parameters, and Surgical Complications in Morbid Obese Bariatric Surgery
      Candidates: a Randomized Clinical Trial.
AB  - OBJECTIVE: To assess which type of preoperative dietary strategy is most
      effective in reducing liver volume and assessing its influence on different
      biochemical parameters and on surgical complications in individuals undergoing
      bariatric surgery. METHODS: Parallel randomized trial comparing the effect of a
      very low calorie diet (VLCD) and a low calorie diet (LCD) for a period of 21 days
      before surgery on hepatic volume, anthropometric and biochemical parameters.
      Compliance and tolerance to the diets, surgical complications, and hospital stay
      were also determined. RESULTS: Eighty-six morbid obese participants undergoing
      bariatric surgery were randomized. The hepatic volume was significantly reduced
      in both intervention groups, but no differences in changes between groups were
      detected. The reduction in the hepatic volume was higher in those patients with a
      baseline hepatic volume > 3 L compared to those with < 3 L (adjusted P value <
      0.001). The percentages of total weight lost were 5.8 and 4.2% (adjusted P value
      = 0.004) for participants on the VLCD and LCD, respectively. There were no
      differences between groups for any of the biochemical parameters analyzed, nor in
      the number of surgical complications nor the length of hospital stay. Adherence
      to the diet was good; nevertheless, participants in the VLCD intervention showed
      worse tolerance. CONCLUSIONS: In subjects with morbid obesity undergoing
      bariatric surgery, compared to a LCD, a preoperative 21-day intervention with
      VLCD is more effective in terms of reducing total body weight but not in terms of
      reducing the liver volume. Both types of preoperative diets have similar effects
      on clinical biochemical parameters, rate of surgical complications, and hospital
      length stay.

PMID- 30109671
TI  - Apical sparing of longitudinal strain in speckle-tracking echocardiography : A
      sensitive and specific finding in cardiac amyloidosis.

PMID- 30109670
TI  - Comparison of Great Curvature Plication with Duodenal-Jejunal Bypass (GCP-DJB)
      and Sleeve Gastrectomy (SG) on Metabolic Indices and Gut Hormones in Type 2
      Diabetes Mellitus Rats.
AB  - OBJECTIVE: The present study compared the therapeutic effects of great curvature
      plication with duodenal-jejunal bypass (GCP-DJB) and the commonly used sleeve
      gastrectomy (SG) in rats with type 2 diabetes mellitus (T2DM). METHODS: The rats
      were randomly divided into three groups: Control group (n = 6), SG group (n = 6),
      and GCP-DJB group (n = 6). Body weight, daily food intake, fasting blood glucose
      level, fasting insulin level, insulin resistance index, and fasting serum
      concentrations of glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine
      (PYY), and bile acid were measured. In addition, postoperative changes in body
      weight and daily food intake at 2, 4, 6, 8, 10, and 12 weeks were also recorded.
      At week 12, an oral glucose tolerance test (OGTT) and insulin release test were
      performed to determine glucose tolerance. The insulin resistance index (IRI) was
      also measured. The postprandial secretion curves and area under the curve (AUC)
      of GLP-1, gastric inhibitory polypeptide (GIP), PYY, and bile acid were also
      calculated. RESULTS: Before surgery, no significant differences in body weight,
      daily food intake, fasting blood glucose, fasting insulin, insulin resistance
      index, fasting GLP-1, PYY, and bile acid were found among the three groups (P >
      0.05). At postoperative week 12, body weight and food intake in the SG and GCP
      DJB groups were lower than those in the Control group (P < 0.05), and body weight
      in the GCP-DJB group was lowest (P < 0.05). Glucose tolerance, postprandial serum
      insulin (INS), GLP-1, PYY, and bile acid were significantly higher in the SG and
      GCP-DJB groups than in the Control group (P < 0.05). The parameters related to
      glucose metabolism in the GCP-DJB group were higher than those in the SG group
      with the exception of serum insulin (P < 0.05). In addition, IRI and GIP
      secretion were significantly lower in the SG and GCP-DJB groups than in the
      Control group (P < 0.05) and were lowest in the GCP-DJB group (P < 0.05).
      CONCLUSION: Both GCP-DJB and SG are surgical options for the treatment of T2DM.
      The underlying mechanism of these treatments may be related to the decrease in
      body weight, food intake, GIP, IRI, and the increase in INS, GLP-1, PYY, and bile
      acid. According to the various metabolic indicators related to the hypoglycemic
      effects in T2DM, GCP-DJB was superior to SG.

PMID- 30109674
TI  - Percutaneous closure of patent foramen ovale for paradoxical embolism in acute
      limb ischemia.

PMID- 30109672
TI  - Fotemustine, teniposide and dexamethasone versus high-dose methotrexate plus
      cytarabine in newly diagnosed primary CNS lymphoma: a randomised phase 2 trial.
AB  - OBJECTIVE: This prospective, randomized, controlled and open-label clinical trial
      sought to evaluate the tolerability and efficacy of the FTD regimen (fotemustine,
      teniposide and dexamethasone) compared to HD-MA therapy (high-dose methotrexate
      plus cytarabine) and to elucidate some biomarkers that influence outcomes in
      patients with newly diagnosed primary CNS lymphoma. METHODS: Participants were
      stratified by IELSG risk score (low versus intermediate versus high) and randomly
      assigned (1:1) to receive four cycles of FTD or HD-MA regimen. Both regimens were
      administered every 3 weeks and were followed by whole-brain radiotherapy. The
      primary endpoints were overall response rate (ORR), progression-free survival
      (PFS) and overall survival (OS). RESULTS: Between June 2012, and June 2015, 52
      patients were enrolled, of whom 49 patients were randomly assigned and analyzed.
      Of the 49 eligible patients, no significant difference was observed in terms of
      ORR between FTD (n = 24) and HD-MA (n = 25) groups (88% versus 84%, respectively,
      P = 0.628). Neither the 2-year PFS nor the 3-year OS rate differed significantly
      between FTD and HD-MA groups (37% versus 39% for 2-year PFS, P = 0.984; 51%
      versus 46% for 3-year OS, P = 0.509; respectively). The HD-MA group showed more
      serious neutropenia (P = 0.009) than the FTD group. High Bcl-6 expression
      correlated with longer OS (P = 0.038). CONCLUSIONS: FTD chemotherapy appeared to
      be safe and effective for PCNSL patients. High Bcl-6 expression correlated with
      longer survival.

PMID- 30109675
TI  - Solid Form of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for
      Minimization of Diacerein Adverse Effects: Development and Bioequivalence
      Evaluation in Albino Rabbits.
AB  - This work aimed to enhance the oral bioavailability of diacerein. The drug was
      incorporated in self-nanoemulsifying drug delivery system. Ternary phase diagrams
      were constructed using CapryolTM90, Miglyol(r)812 and isopropyl myristate as
      oils, Tween(r)80 and Tween(r)20 as surfactants and PEG 200 and PEG 300 as co
      surfactants. Among a total of 432 formulae, 17 formulae were clear. They were
      assessed for mean droplet size, polydispersity index (PDI), saturation solubility
      and transmission electron microscopy. Solid granules were obtained by adsorption
      on Aeroperl(r)300. Results for DSC, PXRD, and SEM of prepared granules revealed
      that diacerein was molecularly dispersed within the formula. Desirability factor
      was adopted to find the granules with maximum solubility, maximum dissolution
      efficiency, maximum dissolution rate and percentage of drug dissolved at 5 min
      and minimum dissolution time and Carr's index. The optimized formula consisted of
      10% Miglyol(r)812, 70% Tween(r)80 and 20% PEG 200 adsorbed to Aeroperl(r) 300
      with a ratio of 2:1 preconcentrate:carrier. It recorded a 3.77-fold increase in
      bioavailability, compared to the marketed product. Such enhancement means lower
      doses and less gastrointestinal side effects.

PMID- 30109673
TI  - Pediatric intracranial ependymoma: correlating signs and symptoms at recurrence
      with outcome in the second prospective AIEOP protocol follow-up.
AB  - PURPOSE: The aims of patients' radiological surveillance are to: ascertain
      relapse; apply second-line therapy; accrue patients in phase 1/2 protocols if
      second-line therapy is not standardized/curative; and assess/treat iatrogenic
      effects. To lessen the emotional and socioeconomic burdens for patients and
      families, we ideally need to establish whether scheduled radiological
      surveillance gives patients a better outcome than waiting for symptoms and signs
      to appear. METHODS: We analyzed a prospective series of 160 newly-diagnosed and
      treated pediatric/adolescent patients with intracranial ependymoma, comparing
      patients with recurrent disease identified on scheduled MRI (the RECPT group; 34
      cases) with those showing signs/symptoms of recurrent disease (the SYMPPT group;
      16 cases). The median follow-up was 67 months. RESULTS: No significant
      differences emerged between the two groups in terms of gender, age, tumor
      grade/site, shunting, residual disease, or type of relapse (local, distant, or
      concomitant). The time to relapse (median 19 months; range 5-104) and the MRI
      follow-up intervals did not differ between the SYMPPT and RECPT groups. The
      presence of signs/symptoms was an unfavorable factor for overall survival (OS)
      after recurrence (5-year OS: 8% vs. 37%, p = 0.001). On multivariable analysis,
      an adjusted model confirmed a significantly worse OS in the SYMPPT than in the
      RECPT patients. CONCLUSIONS: Symptomatic relapses carried a significantly worse
      survival for ependymoma patients than recurrences detected by MRI alone. It would
      therefore be desirable to identify recurrences before symptoms develop.
      Radiological follow-up should be retained in ependymoma patient surveillance
      because there is a chance of salvage treatment for relapses found on MRI.

PMID- 30109676
TI  - Comparative study of the direct black removal by Fe, Cu, and Fe/Cu nanoparticles.
AB  - In this study, direct black dye removal was investigated using iron nanoparticles
      (Fe NPs), copper (Cu NPs), and Fe/Cu (Fe/Cu NPs). NPs were characterized by
      transmission electron microscopy (TEM) and X-ray diffraction (XRD). Using a dose
      of 0.25 g L-1 of Fe, Cu, and Fe/Cu NPs, a degradation efficiency of 13, 26, and
      43% respectively was obtained. For the 1.00 g L-1 dose, the efficiency increased
      to 100, 43, and 100%, respectively. Studies in anoxic and oxic conditions
      presented degradation rates, respectively, of 100 and 30% for Fe NPs, 90 and 50%
      for Fe/Cu NPs, and 40% in both reactions for Cu NPs, indicating that the
      mechanism of dye degradation by NPs is predominantly reducing under the
      conditions studied. The addition of EDTA decreased the dye removal rate for Fe,
      Cu, and Fe/Cu NPs at 27, 10, and 35%, respectively. In addition to the
      degradation, the adsorption phenomena of the by-products formed during the
      reaction were confirmed by the Fourier transform infrared (FTIR) analysis and
      verified by the desorption tests. Fe and Fe/Cu NPs showed the highest efficiency
      in direct black dye reductive degradation and adsorption of by-products, removing
      100% of the dye at a dose of 1 g L-1 within 10 min of reaction. Graphical
      abstracts ?.

PMID- 30109677
TI  - Cellular and compositional insight into the sludge dewatering process using
      enzyme treatment.
AB  - Removal of intracellular water in microbial cells remains a key issue for sludge
      disposal, and here, a novel method of enzymatic treatment with two enzymes,
      lysozyme and protease, was employed. Total internal reflection fluorescence
      microscope (TIRF) was applied to image the bacteria in sludge and quantify the
      evolution of sludge bacteria for the first time. The ratio of dead/live bacterial
      cells was always higher in the presence of lysozyme than in the presence of
      protease, indicating that lysozyme has higher activity in inducing bacterial cell
      degradation and releasing intracellular water. The compositions of extracellular
      polymeric substances (EPS) were further measured, and the results show that the
      dewatering performance of sludge is correlated both to the release of cell
      contents and the variations in EPS composition during cell degradation. Moreover,
      kinetic analysis demonstrated that the enzyme-catalyzed reaction was
      substantially completed within 1 h, i.e., the reaction was quite rapid during the
      first 1 h, and thereafter, it gradually reduced to stability. The mechanism of
      enzymatic treatment of sludge explored in this study thus not only enhanced the
      understanding of sludge deep dewatering but also provided significant
      methodological clues for the disposal of sludge.

PMID- 30109678
TI  - Leachable lead and cadmium in microwave-heated ceramic cups: possible health
      hazard to human.
AB  - In this study, we assessed the leachability as well as health risk associated
      with the consumption from glazed, colourful, ceramic cups, containing lead and
      cadmium. Both metals leached into the 2.5-min microwave-heated (convection mode,
      at 140  degrees C) double-distilled water in concentrations above 0.5 mg/L, the
      permissible limits of leachable Pb and Cd in ceramic mugs set by United States
      Food and Drug Administration (US FDA). On an average, significantly higher Pb
      leached in new cups, 7.69 +/- 0.56 mg/L, compared to that in old cups, 3.15 +/-
      0.15 mg/L. Cd leached similarly in both old (1.97 +/- 0.14 mg/L) and new cups
      (1.57 +/- 0.005 mg/L). The chronic daily intake of Pb by children and adults,
      respectively, consuming from new cups were 1.3-5* and 1.28-6* more than that from
      old cups. In both the cases, intake values far exceeded WHO reference dose of
      0.0006 mg Pb/kg bw/day in children (< 11 years) and 0.0013 mg Pb/kg bw/day in
      adults. Such levels of Pb consumption in children might be predicted to be
      associated with decrement in IQ by at least 1 point and adverse effects in
      adults, especially, women of childbearing age. The daily intake of Cd from these
      cups ranged from 0.002-0.049 mg/kg bw/day, which was also above permissible
      limit. Consequently, high hazard quotient and hazard index (both more than 1)
      were observed for these metals, which might impart individual as well as
      cumulative effects on the health. Thus, apart from other dietary as well as
      inhalation sources of contaminants (which were not studied here), regular
      consumption of beverages alone in glazed, ceramic cups increased chances of Pb-
      and Cd-related health risks to humans.

PMID- 30109679
TI  - The impact of wetland on neutral mine drainage from mining wastes at Luanshya in
      the Zambian Copperbelt in the framework of climate change.
AB  - The impact of a natural wetland ("dambo" in Zambia) on neutral mine drainage at
      Luanshya in the Zambian Copperbelt has been investigated during an intermediate
      discharge period (July) using a multi-method characterization of solid phase
      samples, sequential extraction analysis, X-ray diffraction, Mossbauer
      spectroscopy, and scanning electron microscopy combined with water analyses,
      isotopic analyses, and geochemical modeling. In the wetland, the principal
      identified solid phases in sediments were carbonates, gypsum, and ferric
      oxyhydroxides. A significant portion of the ochres was present as insoluble
      hematite. Mine drainage pH values decrease, and log [Formula: see text] values
      increase after inflow of water into the wetland; dissolved and suspended
      concentrations of Fe, Mn, Cu, and Co also decrease. Based on speciation
      calculations, there is no precipitation of secondary Cu and Co minerals in the
      period of sampling, but it can occur later in dry period when the flow rate is
      reduced. Concentrations of sulfate decrease, and values of delta34S(SO4) in the
      wetland increase in parallel, suggesting sulfate reduction is occurring. In more
      advanced dry period, the discharge in mine drainage stream is probably much lower
      and water can reach supersaturation with respect to minerals such as gypsum,
      which has been found in sediments. Wetlands have a positive impact on mine
      drainage water quality due to the removal of metals by adsorption, co
      precipitation, and filtration of colloids. However, there can also be a rebound
      of contamination by seepage inflow downstream from the wetland. Ongoing climate
      change with extreme hydrologic events may enhance differences between dry and
      rainy seasons with resulting faster mobilization of contaminants.

PMID- 30109680
TI  - Statistical physics modeling of synthetic dyes adsorption onto Spirulina
      platensis nanoparticles.
AB  - Experimental adsorption of synthetic dyes, FD&C red no. 40 and Tartrazine, onto
      Spirulina platensis has been analyzed using a statistical physics treatment at
      different temperatures (298, 308, 318, and 328 K) and at different values of pH
      (4, 6, and 8). The statistical physics formalism was used to develop the
      analytical expressions of models. The interpretation of the adsorption of these
      dyes on Spirulina platensis was achieved by choosing the adequate model and by
      presenting the evolution of the parameters involved in the analytical expression
      of this model such as the number of adsorbed dye molecules per site (nd), the
      receptor sites density (Dr), the adsorbed quantity at saturation (qs), and the
      molar adsorption energy (DeltaE). Thus, several interpretations and results
      describing the adsorption of dyes on Spirulina platensis are extracted regarding
      the behaviors of these parameters at different temperatures and different values
      of pH. Thermodynamic functions such as the Gibbs free energy, the internal
      energy, and the entropy are studied at different values of pH.

PMID- 30109681
TI  - Forecasting CO2 emissions in Hebei, China, through moth-flame optimization based
      on the random forest and extreme learning machine.
AB  - The surge of carbon dioxide emission plays a dominant role in global warming and
      climate change, posing an enormous threat to the development of human being and a
      profound impact on the global ecosystem. Thus, it is essential to analyze the
      carbon dioxide emission change trend through an accurate prediction to inform
      reasonable energy-saving emission reduction measures and effectively control the
      carbon dioxide emission from the source. This paper proposed a hybrid model by
      combining the random forest and extreme learning machine together for the carbon
      dioxide emission forecasting in this paper; the random forest is applied for
      influential factors analysis and the extreme learning machine for the prediction.
      To improve the performance of the prediction model, moth-flame optimization is
      adopted to optimize initial weight and bias in extreme learning machine. A case
      study whose data is derived from Hebei Province, China, during the period 1995
      2015 is conducted to verify the effectiveness of the proposed model. Results show
      that the novel model outperforms the compared parallel models in carbon dioxide
      emission prediction and has the potential to improve the accuracy of CO2 emission
      forecasting.

PMID- 30109682
TI  - Thylacospermum caespitosum population structure and cushion species community
      diversity along an altitudinal gradient.
AB  - As alpine plants, cushion species are particularly susceptible to environment
      changes. Thus, understanding population structure and community diversity
      variation of cushion plants along elevational gradients is crucial for estimating
      their response to predicted climate changes. In this study, Thylacospermum
      caespitosum populations from three elevations (low, medium, and high) in three
      climate zones of China (the Kunlun, Qilian, and Tianshan Mountains) were selected
      to evaluate the effect of elevation on the structure of T. caespitosum
      populations and species diversity of cushion communities. Results showed that
      elevation substantially influenced T. caespitosum populations (size structure,
      density, and death rate), as well as richness (alpha-diversity) and microhabitat
      species pool (species pool) of cushion communities. In the low elevations, T.
      caespitosum populations were in decline due to a lower ratio of small plants and
      higher mortality compared with populations at medium and high elevations. The
      alpha-diversity and species pool in cushion communities were significantly
      increased with decreased elevation, but the importance value of T. caespitosum
      decreased accordingly. Moreover, there was a significant positive correlation
      between elevation and relative importance value (the importance of one species in
      the community) of T. caespitosum (r = 0.883; P < 0.01). Elevation was
      significantly negatively correlated with the mortality rate of T. caespitosum (r
      = - 0.855; P < 0.01), alpha-diversity (r = - 0.933; P < 0.001), and species pool
      (r = - 0.885; P < 0.01). The declining characters of T. caespitosum population
      structure were obvious in low elevation populations. This decline may directly or
      indirectly relate to environmental change. Effects of elevation can provide an
      early indication of range contractions and population declines of cushion species
      with future climate warming. We call for more mechanistic studies of climate
      change impacts on cushion populations, particularly in alpine systems near the
      snow line.

PMID- 30109683
TI  - Wastewater-based epidemiology in low Human Development Index states: bias in
      consumption monitoring of illicit drugs.
AB  - Wastewater-based epidemiology is a promising approach worldwide, and its
      application is currently being developed in non-advanced economies. This
      technology, based on known toxicokinetic data initially used to detect illicit
      drugs in well-managed and maintained local sewer networks, has been extended to
      assess other products such as pesticides, alcohol, flame retardants, nicotine,
      and other substances. This technology is also used in countries with non-advanced
      economies. The present review aims to support future wastewater-based
      epidemiology in such countries by providing toxicokinetic data for locally used
      narcotic drugs that are expected or known to be emerging in developed countries,
      outlining the excretion differences due to human polymorphism, and summarising
      the practical obstacles due to the coverage, maintenance efficiency, or type of
      local sewage network.Case study feedback from Martinique is presented as an
      example; the Martinique field study complies with the Organisation for Economic
      Co-operation and Development standards for health issues, but not with regard to
      population and urban dynamics.

PMID- 30109684
TI  - Diagnosis and ecotoxicological risk assessment of 49 elements in sludge from
      wastewater treatment plants of Chongqing and Xiamen cities, China.
AB  - Limited information about the sludge quality is a major constraint for its usage
      and proper disposal. This study investigated the occurrence of 49 elements in
      sludge from 11 wastewater treatment plants (WWTPs) in Chongqing and Xiamen cities
      of China. The concentration of 46-detected elements ranged from 16.2 MUg kg-1
      (Pt) to 55.0 g kg-1 (Al) on dry solid basis in the sludge. The enrichment factor
      of most of the elements was > 1.5, indicating their possible anthropogenic
      origin. The precious metals had considerably higher enrichment factor ranging
      from 56.3 to 200,000. Principal component analysis clustered the samples from
      Chongqing and Xiamen separately to suggest strong spatial variations.
      Contamination factor, pollution loading index, and integrated pollution degree
      were calculated to evaluate the elemental pollution risk. The pollution loading
      index indicated unpolluted to highly polluted levels of the elements in the
      sludge. In addition, results from the ecotoxicological risk index showed an
      individual low to very high ecotoxicological risk posed by eight metal(loid)s
      (As, Cd, Cr, Cu, Mn, Ni, Pb, and Zn) in the WWTPs.

PMID- 30109685
TI  - Environmental photochemical fate and UVC degradation of sodium levothyroxine in
      aqueous medium.
AB  - The synthetic hormone sodium levothyroxine (LTX) is one of the most prescribed
      drugs in the world and the most effective in hypothyroidism treatment. The
      presence of LTX in the environment has become a matter of major concern due to
      the widespread use of this hormone and by the fact that it is only partially
      removed in conventional water and sewage treatment plants. However, information
      regarding the photochemical fate of this hormone in environmental or engineered
      systems is scarce in the literature. In this work, the sunlight-driven direct and
      indirect LTX degradation was investigated by determining the photolysis quantum
      yield, PhiLTX = 3.80 (+/- 0.02) * 10-5, as well as the second-order kinetic
      constants of the reactions with hydroxyl radicals, kLTX,*OH = 1.50 (+/- 0.01) *
      1010 L mol-1 s-1 and singlet oxygen, kLTX,1O2 = 1.47 (+/- 0.66) * 108 L mol-1 s
      1. Mathematical simulations indicate that LTX photodegradation is favored in
      shallow, nitrite-rich, and dissolved organic matter (DOM)-poor environments, with
      LTX half-life times varying from less than 10 days to about 80 days. LTX removals
      of 85 and 95% were achieved by UVC photolysis and UVC/H2O2 after 120 min,
      respectively. Three transformation products, triiodothyronine, diiodothyronine,
      and diiodotyrosine, were identified during LTX degradation by the UVC-based
      processes studied. The results herein regarding photo-induced kinetics coupled
      with environmental fate simulations may help evaluate LTX persistence and also
      the design of water and wastewater treatment processes.

PMID- 30109686
TI  - Removal mechanism of sulfamethazine and its intermediates from water by a
      rotating advanced oxidation contactor equipped with TiO2-high-silica zeolite
      composite sheets.
AB  - The removal of antibiotic sulfamethazine (SMT) and its intermediates from water
      was investigated using a rotating advanced oxidation contactor (RAOC) equipped
      with TiO2-high-silica zeolite composite sheets. SMT was readily removed from
      water through adsorption onto high-silica zeolite and photocatalytic
      decomposition by TiO2 inside the composite sheet. Some degradation intermediates
      were retained and photocatalytically decomposed inside the composite sheet.
      Relatively hydrophobic intermediates such as hydroxylated SMT were captured
      inside the sheets, whereas hydrophilic intermediates were distributed in water.
      This was attributed to the hydrophobic interactions in the adsorption mechanism
      of high-silica zeolite. The time courses of the NH4+, NO3-, and SO42- ion
      concentration during the RAOC treatment of SMT were evaluated. After treatment by
      RAOC for 24 h, approximately 94% of nitrogen derived from the amino and
      sulfanilamide groups and 39% of sulfur from the sulfanilamide group were
      mineralized, which indicated that the mineralization behavior of SMT treated by
      RAOC was different from that treated by TiO2 powder. These results strongly
      suggested that the dissociation of the amino group and cleavage of the
      sulfonamide group and subsequent dissociation of the amino group preferentially
      proceeded inside the composite sheets.

PMID- 30109687
TI  - Vermicompost addition influences symbiotic fungi communities associated with leek
      cultivated in metal-rich soils.
AB  - In the context of urban agriculture, where soils are frequently contaminated with
      metal(loid)s (TM), we studied the influence of vermicompost amendments on
      symbiotic fungal communities associated with plants grown in two metal-rich
      soils. Leek (Allium porrum L.) plants were grown with or without vermicompost in
      two metal-rich soils characterized by either geogenic or anthropogenic TM
      sources, to assess the influence of pollutant origin on soil-plant transfer.
      Fungal communities associated with the leek roots were identified by high
      throughput Illumina MiSeq and TM contents were measured using mass spectrometry.
      Vermicompost addition led to a dramatic change in the fungal community with a
      loss of diversity in the two tested soils. This effect could partially explain
      the changes in metal transfer at the soil-AMF-plant interface. Our results
      suggest being careful while using composts when growing edibles in contaminated
      soils. More generally, this study highlights the need for further research in the
      field of fungal communities to refine practical recommendations to gardeners.
      Graphical abstract.

PMID- 30109688
TI  - Microplastics in Talitrus saltator (Crustacea, Amphipoda): new evidence of
      ingestion from natural contexts.
AB  - Using Fourier transform infrared spectroscopy (FT-IR) measurements and comparing
      the spectrum peaks (range 4000-600 cm-1) with reference spectra database and
      instrument libraries, we observed new evidence of the ingestion of microplastic
      particles analyzing the digestive tracts of Talitrus saltator. Specimens, sampled
      in central Italy, probably ingested the particles with natural detritus. Since
      worldwide many species of invertebrates and vertebrates (e.g., birds) feed on
      Amphipoda along coastal ecosystems, we hypothesized that microplastic in these
      crustaceans can be accumulated along the food chain.

PMID- 30109689
TI  - Cd and Pb accumulation characteristics of phytostabilizer Athyrium wardii (Hook.)
      grown in soils contaminated with Cd and Pb.
AB  - Interactions between heavy metals in soil could affect soil heavy metal
      availability and plant uptake. Thus, in this study, Cd and Pb accumulation as
      well as plant growth of the mining ecotype (ME) and non-mining ecotype (NME) of
      Athyrium wardii (Hook.) in response to the exposure of Cd and Pb was investigated
      by a pot experiment. Although the exposure of Cd in combination with Pb further
      inhibited the growth of the two ecotypes in comparison with the exposure of
      single Cd or Pb, the ME presented lower biomass decline for the whole plant
      (22.0%-70.0%) than the NME among most treatments. The presence of Pb promoted Cd
      accumulation both in above-ground and under-ground parts of the ME. Cd
      concentrations in under-ground parts of the ME decreased when exposed to higher
      concentrations of Pb (> 600 mg kg-1). Meanwhile, the presence of Cd inhibited Pb
      accumulation in above-ground parts of the ME and promoted Pb accumulation in
      under-ground parts of the ME. Pb concentrations in under-ground parts of the ME
      decreased when soil Cd concentrations were more than 25 mg kg-1. The partial
      correlation analysis further demonstrated that the interactions between Cd and Pb
      stimulated Cd accumulation both in above-ground and under-ground parts of the ME
      and Pb accumulation in under-ground parts of the ME, while inhibited Pb
      accumulation in above-ground parts of the ME, showing great benefit for Pb
      phytostabilization by the ME. Among treatments, the bioaccumulation coefficients
      for Cd and Pb of the ME, varying from 2.71-31.05 and 20.09-78.06, were much
      higher than those of the NME. The translocation factors for Cd and Pb of the ME,
      varying from 0.26-0.52 and 0.01-0.10, were lower than those of the NME. These
      results indicate that the ME presented greater potential for the
      phytostabilization of soil contamination with Cd and Pb, especially for Pb.

PMID- 30109690
TI  - Eliminating redundant spatial variation to better understand the variance of
      interest of soil potentially toxic elements at different sampling scales in
      different soil types south of Nanjing, China.
AB  - Sampling scale and prediction of spatial distribution are essential in surveys of
      soil metal pollution. Sufficient sampling density encompassing the principal
      spatial sources of variance and prediction of polluted areas with the help of
      soil maps makes pollution evaluation more reliable and subsequent soil
      remediation assessment more efficient. Two soil sampling schemes, using 232
      points at 2-km intervals in 2002 for sampling at county scale and 109 points at
      200-1000-m intervals in 2012 at town scale, were used to study the potentially
      toxic metals Cu, Cd, Cr, Hg, Ni, Pb, Zn, and the metalloid As in an urban-rural
      hinge area. We focused on finding characteristics of the explanatory power of
      soil type toward different sampling scales from 200 to 2000 m, a routine sampling
      scale in practice for remediation of soil potentially toxic elements (PTEs). We
      also attempted to eliminate the redundant spatial variation to better understand
      the variance of soil PTEs. Spatial variation of PTEs at different scales was
      compared and estimated using soil map units based on geostatistical methods. The
      explanatory power of the soil map units selected at different scales was
      significantly different at P < 0.01 and the smaller scales better explained the
      spatial variance. Anthropic activities profoundly affected the contents of PTEs
      in soils and the amounts of anthropogenic pollutants released often exceed the
      contribution from natural sources. Variances of interest of Cr and Cu were
      underestimated by 72.4 and 32.8%, respectively, due to soil type as a factor but
      were overestimated for other elements by percentages following the sequence Zn
      (45.4%) > Hg (28.6%) > Pb (28.8%) > Ni (26.73%) > As (13.7%) > Cd (10.5%).
      Eliminating variances of zero interest would be helpful in increasing the
      effectiveness of remediation of metal-contaminated soils.

PMID- 30109691
TI  - Facile and environmental benign in situ synthesis of silver nanoparticles for
      multifunctionalization of wool fibers.
AB  - In this manuscript, we report the simple method to multifunctional wool fiber
      surfaces. The multifunctional wool fibers were devised with brilliant coloration,
      antimicrobial activity, and UV-protection property. These multifunctional
      properties were progressed by in situ assemble of silver nanoparticles (Ag NPs)
      into the wool fiber surface using green cleaner one-pot route. The proteins
      existing in the wool fibers acted being a redox active bio-template, facilitating
      the reduction of Ag+ to Ag0, with simultaneous binding of the produced Ag NPs
      both on the surface and within the center of the wool fibers. The entire results
      showed that the Ag NP in situ-incorporated wool fibers can be used as colorant
      wool fibers effectively, and these colored fibers also exhibit an improvement for
      multi-functionality properties.

PMID- 30109693
TI  - Evaluation of the disintegration of linen fabric under composting conditions.
AB  - In recent years, about 10% of the total wastes generated around the world were
      fabric wastes and, due to the large volume of these wastes, should be well
      managed. Among the various types of fabrics, some have greater biodegradability
      and can be decomposed at the acceptable rates under controlled conditions. In
      this study, the disintegration of linen fabric was investigated under composting
      conditions. During the composting process, temperature, moisture, and aeration
      were controlled. According to FTIR spectra of linen fabrics during the composting
      process, the disintegration of linen fibers was identified as the breakdown of
      carbonyl groups and hydrogen bonds of cellulosic chains. Regarding the SEM images
      of linen fabrics, the composting process in the first 45 days led to the
      breakdown of the fibers, and in the second 45 days of the process, most of the
      fibers were degraded. Since in the second 45 days of the process, the compost
      pile temperature is always between 39 and 44  degrees C and 65-70  degrees C, it
      can be concluded that the rate of microbial disintegration of the linen fabric is
      higher at these temperatures. At the end of the test, the disintegration value of
      the linen fabric was 55% and the weight loss due to organic matter conversion was
      61%. The samples weight loss showed that linen fabric has high biodegradability
      under composting conditions. The germination index (GI) of the resulting compost
      was 73.88%, which indicates the produced compost is mature.

PMID- 30109694
TI  - Is the informal economic activity a determinant of environmental quality?
AB  - This study aims to investigate whether the size of the informal economic activity
      is a determinant of the environmental quality in the case of Turkey. First, the
      MIMIC model approach will be used to estimate the size of the informal economic
      activity. Second, time series analysis will be conducted for the period from 1970
      to 2014, in order to examine the effect of the size of the informal economic
      activity on the environmental quality by conducting Carrion-i-Silvestre et al.
      (Economet Theor 25:1754, 2009) unit root tests, Bound test and Maki (Econ Model
      29:2011-2015, 2012) cointegration tests that allow structural breaks will be
      employed prior to the DOLS, FMOLS, and ARDL approaches for long-run and short-run
      models. The results suggest that informal economic activity is a positively
      significant determinant on the environmental quality. Moreover, this paper
      suggests that both formal and informal economies have significant impact on
      environmental quality. However, formal economy exerts positively higher effects
      on the environmental quality compared to informal economy. Turkish authorities
      need to pay more attention on both formal and informal economic activities to
      prevent environmental degradation in Turkey.

PMID- 30109692
TI  - Effects of microplastics on trophic parameters, abundance and metabolic
      activities of seawater and fish gut bacteria in mesocosm conditions.
AB  - Plastic pollution is an emerging threat with severe implications on animals' and
      environmental health. Nevertheless, interactions of plastic particles with both
      microbial structure and metabolism are a new research challenge that needs to be
      elucidated yet. To improve knowledge on the effects played by microplastics on
      free-living and fish gut-associated microbial community in aquatic environments,
      a 90-day study was performed in three replicated mesocosms (control-CTRL, native
      polyvinyl chloride-MPV and weathered polyvinyl chloride-MPI), where sea bass
      specimens were hosted. In CTRL mesocosm, fish was fed with no-plastic-added food,
      whilst in MPV and MPI food was supplemented with native or exposed to polluted
      waters polyvinylchloride pellets, respectively. Particulate organic carbon (POC)
      and nitrogen, total and culturable bacteria, extracellular enzymatic activities,
      and microbial community substrate utilization profiles were analyzed. POC values
      were lower in MPI than MPV and CRTL mesocosms. Microplastics did not affect
      severely bacterial metabolism, although enzymatic activities decreased and
      microbes utilized a lower number of carbon substrates in MPI than MPV and CTRL.
      No shifts in the bacterial community composition of fish gut microflora were
      observed by denaturing gradient gel electrophoresis fingerprinting analysis.

PMID- 30109695
TI  - TYRP1:c.555T>G is a recurrent mutation found in Australian Shepherd and Miniature
      American Shepherd dogs.

PMID- 30109696
TI  - Genome-wide association mapping and examination of possible maternal effect for
      the pace trait of horses.
AB  - Previously, a single nucleotide polymorphism (SNP) related to gait type was
      identified at position 22 999 655 of chromosome 23 in the coding region of DMRT3
      (DMRT3:Ser301Ter) by showing that a cytosine (C) to adenine (A) mutation of this
      SNP induced pace in the Icelandic horse. We investigated the effect of
      DMRT3:Ser301Ter on the gait of Hokkaido Native Horses, a Japanese native breed,
      and examined genetic factors other than DMRT3 by exploring genome-wide SNPs
      related to gait determination. All animals exhibiting pace were AA for
      DMRT3:Ser301Ter, confirming the association of DMRT3:Ser301Ter with gait
      determination; however, 14.3% of the animals exhibiting trot also had AA for
      DMRT3:Ser301Ter, suggesting the presence of another factor(s) cooperatively
      working with DMRT3:Ser301Ter for gait determination. SNPs on chromosomes 13 and
      23 were detected by genome-wide association analysis (false discovery rate
      <0.05), although SNPs on chromosome 23 were all located in the vicinity of
      DMRT3:Ser301Ter, confirming the association with DMRT3. A genome-wide association
      study targeting only animals with AA for DMRT3:Ser301Ter to examine genetic
      factors cooperatively working with DMRT3:Ser301Ter for gait determination
      suggested associations of 23 SNPs on six chromosomes. In a series of analyses of
      the effect of a maternal factor (dam's gait) on gait determination, the effect
      was suggested in comparison of the frequencies of exhibiting pace in gait checks
      in only two animal groups having dams with different DMRT3:Ser301Ter genotypes (P
      < 0.05), suggesting that the gait of the dam does not have a major effect on
      whether progeny homozygous for the DMRT3:Ser301Ter mutation will preferentially
      pace or trot.

PMID- 30109698
TI  - Use of antimicrobial agent pocket irrigation for cardiovascular implantable
      electronic device infection prophylaxis: Results from an international survey.
AB  - PURPOSE: Survey the usage and application protocol of antimicrobial agent pocket
      irrigation for cardiovascular implantable electronic device (CIED) infection
      prophylaxis. BACKGROUND: Local antibiotic usage for CIED infection prophylaxis,
      in particular pocket irrigation, is a well-known strategy but with little data on
      its clinical effectiveness. METHODS: An anonymous voluntary online survey was
      sent to a total of 2,092 arrhythmia-oriented cardiologists in 51 countries (1,490
      from the United States). RESULTS: There were 487 responses (response rate 23.3%:
      U.S. 28.2%, outside of the U.S. 11.1%). Eighty-seven percent of respondents use
      intraoperative antimicrobial agent pocket irrigation and/or an antimicrobial
      eluting pouch to reduce CIED infection. Fifty-four percent of respondents believe
      that it is effective to use an antimicrobial agent pocket irrigation to reduce
      CIED infection; 33% of respondents are uncertain; a few consider this strategy
      ineffective (13%) or offered no opinion. Significant differences exist in the
      practice patterns and beliefs between the U.S. and non-U.S. countries (P < 0.05).
      Ninety-eight percent of respondents report using the same pocket irrigation
      protocol for permanent pacemaker versus implantable cardioverter defibrillator.
      Bacitracin (48%), vancomycin (39%), and a cephalosporin (29%) are the most
      commonly chosen antibiotics. A majority of the respondents are unaware of the
      cost of using antimicrobial agent pocket irrigation (69%) and neither are they
      concerned (67%). CONCLUSION: This international survey suggests that, while there
      are little clinical data to support or discourage such practice, the usage of
      antimicrobial agent pocket irrigation for CIED infection prophylaxis is widely
      used in current practice.

PMID- 30109697
TI  - Prior exercise training improves cold tolerance independent of indices associated
      with non-shivering thermogenesis.
AB  - KEY POINTS: Mammals defend against cold-induced reductions in body temperature
      through both shivering and non-shivering thermogenesis. The activation of non
      shivering thermogenesis is primarily driven by uncoupling protein-1 in brown
      adipose tissue and to a lesser degree by the browning of white adipose tissue.
      Endurance exercise has also been shown to increase markers of white adipose
      tissue browning. This study aimed to determine whether prior exercise training
      would alter the response to a cold challenge and if this would be associated with
      differences in indices of non-shivering thermogenesis. It is shown that exercise
      training protects against cold-induced weight loss by increasing food intake.
      Exercise-trained mice were better able to maintain their core temperature,
      independent of differences in markers of non-shivering thermogenesis. ABSTRACT:
      Shivering is one of the first defences against cold, and as skeletal muscle
      fatigues there is an increased reliance on non-shivering thermogenesis. Brown and
      beige adipose tissues are the primary thermogenic tissues regulating this
      process. Exercise has also been shown to increase the thermogenic capacity of
      subcutaneous white adipose tissue. Whether exercise has an effect on the
      adaptations to cold stress within adipose tissue and skeletal muscle remains to
      be shown. Male C57BL/6 mice were either subjected to voluntary wheel running or
      remained sedentary for 12 days. Exercise led to decreased body weight and
      increased glucose tolerance. Mice were then divided into groups kept at 25
      degrees C room temperature or a cold challenge of 4 degrees C for 48 h. Exercised
      mice were protected against cold-induced reductions in weight and in parallel
      with increased food intake. Providing exercised mice with the same amount of food
      as sedentary mice eliminated the protection against cold-induced weight loss.
      Cold exposure led to greater reductions in rectal temperature in sedentary
      compared to exercised mice. This protective effect was not explained by
      differences in the browning of white adipose tissue or brown adipose tissue mass.
      Similarly, the ability of the beta3 -adrenergic agonist CL 316,243 to increase
      energy expenditure was attenuated in previously exercised mice, suggesting that
      the activation of uncoupling protein-1 in brown and/or beige adipocytes is not
      the source of protective effects. We speculate that the protection against cold
      induced reductions in rectal temperature could potentially be linked to exercise
      induced alterations in skeletal muscle.

PMID- 30109699
TI  - Predictors of survival after resection of primary sarcomas of the chest wall-A
      large, single-institution series.
AB  - BACKGROUND AND OBJECTIVES: Chest wall sarcomas are rare and may demonstrate
      heterogeneous features. Surgery remains the mainstay of treatment with
      chemotherapy and radiotherapy used as adjuncts. Herein, we report outcomes of a
      large cohort of patients with primary chest wall sarcoma who underwent resection.
      METHODS: Records of 121 patients who underwent resection for primary chest wall
      sarcoma between 1998 and 2013 were reviewed. A thoracic pathologist reexamined
      all tumors and categorized them according to grade. Univariable and multivariable
      Cox analyses were conducted to identify predictors of overall survival (OS).
      RESULTS: The median age was 45.0 (range, 11-81) years, and most tumors (63.6%,
      77) were high grade. The median tumor size was 7 cm (range, 1-21 cm). Fifty-nine
      (48.8%) patients received neoadjuvant chemotherapy and 12 (9.9%) received
      neoadjuvant radiotherapy. A complete resection was achieved in 103 (85.1%)
      patients. Neoadjuvant chemotherapy (P = 0.532) and radiation ( P = 1.000) were
      not associated with a complete resection. Five-year OS among patients undergoing
      R0 and R1 resections was 61.9% and 27.8%, respectively. Multivariable analysis
      identified high grade (HR, 15.21; CI, 3.57-64.87; P < 0.001), R1 (HR, 3.10; CI,
      1.40-6.86; P = 0.005), R2 resection (HR, 5.18; CI, 1.91-14.01; P = 0.001), and
      age (HR, 1.02; CI, 1.01-1.03; P = 0.002) as predictors of OS. CONCLUSIONS: In
      this series of resected chest wall sarcomas, complete resection and tumor grade
      remain the most important survival predictors. Individual decisions are required
      for the utilization of neoadjuvant therapy.

PMID- 30109700
TI  - Valproate-associated foetal malformations-Rates of occurrence, risks in attempted
      avoidance.
AB  - OBJECTIVES: To gain insight into the main advantages and disadvantages that might
      result from valproate being unavailable for women who intend to become pregnant.
      MATERIALS AND METHODS: Analysis of data from the Australian Pregnancy Register
      concerning pregnancies exposed to valproate (N = 501) and pregnancies where
      previous valproate intake had been ceased before pregnancy (N = 101). RESULTS:
      The risk of foetal malformation associated with valproate exposure during
      pregnancy was dose-related, and there was a tendency for the more major
      malformations, including those often managed by therapeutic abortion, for example
      spina bifida, to occur at higher valproate doses. Had there been no exposure to
      valproate during pregnancy, some 80% of the foetal malformations that occurred
      might have been avoided. Cessation of previous valproate therapy before pregnancy
      was associated with an increased hazard of seizure-affected pregnancy. This was
      particularly the case for women with generalized epilepsies, in whom the
      incidence of seizure-affected pregnancy was increased by 50% to nearly 100%.
      CONCLUSIONS: Avoiding valproate intake during pregnancy is likely to reduce the
      incidence of foetal malformation, but at a cost of worsened maternal epilepsy
      control. Individualization of treatment is particularly important in considering
      withdrawal of valproate in the light of the fact that it is much more widely used
      in generalized epilepsy, there being fewer alternative drugs than for focal
      epilepsy and withdrawal is not without risk for both mother and baby. This study
      may provide a quantitative basis for assessing the balance between benefit and
      disadvantage for individual women with valproate-treated epilepsy who are
      considering pregnancy.

PMID- 30109701
TI  - Transabdominal ultrasound and endoscopic ultrasound for diagnosis of gallbladder
      polyps.
AB  - BACKGROUND: Approximately 0.6% to 4% of cholecystectomies are performed because
      of gallbladder polyps. The decision to perform cholecystectomy is based on
      presence of gallbladder polyp(s) on transabdominal ultrasound (TAUS) or
      endoscopic ultrasound (EUS), or both. These polyps are currently considered for
      surgery if they grow more than 1 cm. However, non-neoplastic polyps (pseudo
      polyps) do not need surgery, even when they are larger than 1 cm. True polyps are
      neoplastic, either benign (adenomas) or (pre)malignant (dysplastic
      polyps/carcinomas). True polyps need surgery, especially if they are premalignant
      or malignant. There has been no systematic review and meta-analysis on the
      accuracy of TAUS and EUS in the diagnosis of gallbladder polyps, true gallbladder
      polyps, and (pre)malignant polyps. OBJECTIVES: To summarise and compare the
      accuracy of transabdominal ultrasound (TAUS) and endoscopic ultrasound (EUS) for
      the detection of gallbladder polyps, for differentiating between true and pseudo
      gallbladder polyps, and for differentiating between dysplastic polyps/carcinomas
      and adenomas/pseudo polyps of the gallbladder in adults. SEARCH METHODS: We
      searched the Cochrane Library, MEDLINE, Embase, Science Citation Index Expanded,
      and trial registrations (last date of search 09 July 2018). We had no
      restrictions regarding language, publication status, or prospective or
      retrospective nature of the studies. SELECTION CRITERIA: Studies reporting on the
      diagnostic accuracy data (true positive, false positive, false negative and true
      negative) of the index test (TAUS or EUS or both) for detection of gallbladder
      polyps, differentiation between true and pseudo polyps, or differentiation
      between dysplastic polyps/carcinomas and adenomas/pseudo polyps. We only accepted
      histopathology after cholecystectomy as the reference standard, except for
      studies on diagnosis of gallbladder polyp. For the latter studies, we also
      accepted repeated imaging up to six months by TAUS or EUS as the reference
      standard. DATA COLLECTION AND ANALYSIS: Two authors independently screened
      abstracts, selected studies for inclusion, and collected data from each study.
      The quality of the studies was evaluated using the QUADAS-2 tool. The bivariate
      random-effects model was used to obtain summary estimates of sensitivity and
      specificity, to compare diagnostic performance of the index tests, and to assess
      heterogeneity. MAIN RESULTS: A total of 16 studies were included. All studies
      reported on TAUS and EUS as separate tests and not as a combination of tests. All
      studies were at high or unclear risk of bias, ten studies had high applicability
      concerns in participant selection (because of inappropriate participant
      exclusions) or reference standards (because of lack of follow-up for non-operated
      polyps), and three studies had unclear applicability concerns in participant
      selection (because of high prevalence of gallbladder polyps) or index tests
      (because of lack of details on ultrasound equipment and performance). A meta
      analysis directly comparing results of TAUS and EUS in the same population could
      not be performed because only limited studies executed both tests in the same
      participants. Therefore, the results below were obtained only from indirect test
      comparisons. There was significant heterogeneity amongst all comparisons (target
      conditions) on TAUS and amongst studies on EUS for differentiating true and
      pseudo polyps.Detection of gallbladder polyps: Six studies (16,260 participants)
      used TAUS. We found no studies on EUS. The summary sensitivity and specificity of
      TAUS for the detection of gallbladder polyps was 0.84 (95% CI 0.59 to 0.95) and
      0.96 (95% CI 0.92 to 0.98), respectively. In a cohort of 1000 people, with a 6.4%
      prevalence of gallbladder polyps, this would result in 37 overdiagnosed and seven
      missed gallbladder polyps.Differentiation between true polyp and pseudo
      gallbladder polyp: Six studies (1078 participants) used TAUS; the summary
      sensitivity was 0.68 (95% CI 0.44 to 0.85) and the summary specificity was 0.79
      (95% CI 0.57 to 0.91). Three studies (209 participants) used EUS; the summary
      sensitivity was 0.85 (95% CI 0.46 to 0.97) and the summary specificity was 0.90
      (95% CI 0.78 to 0.96). In a cohort of 1000 participants with gallbladder polyps,
      with 10% having true polyps, this would result in 189 overdiagnosed and 32 missed
      true polyps by TAUS, and 90 overdiagnosed and 15 missed true polyps by EUS. There
      was no evidence of a difference between the diagnostic accuracy of TAUS and EUS
      (relative sensitivity 1.06, P = 0.70, relative specificity 1.15, P =
      0.12).Differentiation between dysplastic polyps/carcinomas and adenomas/pseudo
      polyps of the gallbladder: Four studies (1,009 participants) used TAUS; the
      summary sensitivity was 0.79 (95% CI 0.62 to 0.90) and the summary specificity
      was 0.89 (95% CI 0.68 to 0.97). Three studies (351 participants) used EUS; the
      summary sensitivity was 0.86 (95% CI 0.76 to 0.92) and the summary specificity
      was 0.92 (95% CI 0.85 to 0.95). In a cohort of 1000 participants with gallbladder
      polyps, with 5% having a dysplastic polyp/carcinoma, this would result in 105
      overdiagnosed and 11 missed dysplastic polyps/carcinomas by TAUS and 76
      overdiagnosed and seven missed dysplastic polyps/carcinomas by EUS. There was no
      evidence of a difference between the diagnostic accuracy of TAUS and EUS (log
      likelihood test P = 0.74). AUTHORS' CONCLUSIONS: Although TAUS seems quite good
      at discriminating between gallbladder polyps and no polyps, it is less accurate
      in detecting whether the polyp is a true or pseudo polyp and dysplastic
      polyp/carcinoma or adenoma/pseudo polyp. In practice, this would lead to both
      unnecessary surgeries for pseudo polyps and missed cases of true polyps,
      dysplastic polyps, and carcinomas. There was insufficient evidence that EUS is
      better compared to TAUS in differentiating between true and pseudo polyps and
      between dysplastic polyps/carcinomas and adenomas/pseudo polyps. The conclusions
      are based on heterogeneous studies with unclear criteria for diagnosis of the
      target conditions and studies at high or unclear risk of bias. Therefore, results
      should be interpreted with caution. Further studies of high methodological
      quality, with clearly stated criteria for diagnosis of gallbladder polyps, true
      polyps, and dysplastic polyps/carcinomas are needed to accurately determine
      diagnostic accuracy of EUS and TAUS.

PMID- 30109702
TI  - Cutaneous anaesthesia of hip surgery incisions with iliohypogastric and subcostal
      nerve blockade: A randomised trial.
AB  - BACKGROUND: Cutaneous nerve blockade may improve analgesia after hip surgery.
      Anaesthesia after the lateral femoral cutaneous (LFC) nerve block is too distal
      for complete coverage of most hip surgery incisions, which requires additional
      anaesthesia of the adjacent, proximal area. The transversalis fascia plane (TFP)
      block potentially anaesthetises the iliohypogastric and subcostal nerves. The
      primary aim of the present study was to investigate, if the TFP block provides
      cutaneous anaesthesia adjacent to the LFC nerve block. METHODS: Active vs placebo
      TFP blocks were compared in a paired randomised controlled trial (RCT) in 20
      volunteers, who all had bilateral LFC nerve blocks. The day preceding the RCT,
      the area anaesthetised by a novel selective ultrasound guided subcostal nerve
      block was identified bilaterally in order to assess the contribution of the
      subcostal nerve to the area anaesthesia by the TFP block. RESULTS: Anaesthesia of
      the lateral hip region after TFP block was 80%. The cutaneous anaesthesia after
      active TFP block was in continuity with the LFC nerve block in 65%. Combined TFP
      and LFC nerve blockade significantly increased the coverage of hip surgery
      incisions compared to LFC nerve block alone. The success rate of blocking the
      subcostal nerve was 50% with the TFP block. CONCLUSION: The TFP block
      anaesthetises the skin proximal to the LFC nerve block by anaesthetising the
      iliohypogastric and subcostal nerves. TFP block as a supplement to LFC nerve
      block improves the coverage of the proximal surgical incisions used for hip
      surgery.

PMID- 30109703
TI  - Changes in tissue oxygen tension, venous saturation, and Fick-based assessments
      of cardiac output during hyperoxia.
AB  - BACKGROUND: Hyperoxemia (arterial oxygen tension >100 mm Hg) may occur in
      critically ill patients and have effects on mixed venous saturation (SvO2 ) and
      on Fick-based estimates of cardiac output (CO). We investigated the effect of
      hyperoxemia on SvO2 and on assessments of CO using the Fick equation. METHODS:
      Yorkshire swine (n = 14) were anesthetized, intubated, and paralyzed for
      instrumentation. SvO2 (co-oximetry) and tissue oxygen tension (tPO2 , implantable
      electrodes) in brain and myocardium were measured during systematic manipulation
      of arterial oxygen tension (PaO2 ) using graded hyperoxia (fraction of inspired
      oxygen 0.21 -> 0.8). Secondarily, oxygen- and carbon dioxide-based estimates of
      CO (FickO2 and FickCO 2 , respectively) were compared with measurements from a
      flow probe placed on the aortic root. RESULTS: Independent of changes in measured
      oxygen delivery, cerebral and myocardial tPO2 increased in proportion to PaO2 ,
      as did SvO2 (P < 0.001 for all). Based on mixed model analysis, each 100 mm Hg
      increase in PaO2 resulted in a 4.8 +/- 0.9% increase in SvO2 under the conditions
      tested. Because neither measured oxygen consumption, arterial oxyhemoglobin
      saturation or cardiac output varied significantly during hyperoxia, changes in
      SvO2 resulted in successively increasing errors in FickO2 during hyperoxia (34%
      during normoxia, 72% during FiO2 0.8). FickCO 2 lacked the progressively
      worsening errors present in FickO2 , but correlated poorly with CO. CONCLUSION:
      SvO2 acutely changes following changes in PaO2 even absent changes in measured
      DO2 . This may lead to errors in FickO2 estimates of CI. Further work is
      necessary to understand the impact of this phenomenon in disease states.

PMID- 30109705
TI  - AKI - biomarkers - neonatal cardiac surgery. No answer yet.

PMID- 30109704
TI  - Optical coherence tomography in acute optic neuritis: A population-based study.
AB  - OBJECTIVES: To measure early structural damage caused by autoimmune inflammatory
      optic neuritis (ON) by optical coherence tomography (OCT) in a population-based
      cohort. METHODS: In a prospective population-based study over 24 months in
      Southern Denmark, patients diagnosed with acute ON and without prior diagnosis of
      a chronic neuroinflammatory disorder were included and examined with OCT, visual
      evoked potentials (VEP), visual fields, high contrast visual acuity (HCVA), and
      low contrast letter acuity (LCLA). Structural and functional outcomes were
      determined at 6-month follow-up based on interocular differences. RESULTS: The 50
      included patients had on average 16.9 MUm peripapillary retinal nerve fiber layer
      loss, 10.6 MUm ganglion cell and inner plexiform layer (GCIP) loss, and an
      average HCVA decrease of 0.22 dec. Based on a linear regression model, average
      GCIP loss amounted to -0.2 MUm per day and started 8 days after onset. OCT
      outcomes but not VEP correlated well with all visual function measurements at
      follow-up. Structural and functional damage in 20 patients (40%) diagnosed de
      novo with multiple sclerosis (MS) and in 2 patients (4%) with positive myelin
      oligodendrocyte glycoprotein antibodies (MOG-IgG) test did not differ from
      patients with idiopathic ON. CONCLUSIONS: Optic neuritis causes substantial
      retinal damage and vision loss independent of the underlying disease. Our study
      supports that GCIP damage starts closely to clinical onset. Good structure
      function correlations between OCT and vision support the importance of OCT in
      monitoring acute ON.

PMID- 30109706
TI  - Asymmetric evolutionary responses to sex-specific selection in a hermaphrodite.
AB  - Sex allocation theory predicts that simultaneous hermaphrodites evolve to an
      evolutionary stable resource allocation, whereby any increase in investment to
      male reproduction leads to a disproportionate cost on female reproduction and
      vice versa. However, empirical evidence for sexual trade-offs in hermaphroditic
      animals is still limited. Here, we tested how male and female reproductive traits
      evolved under conditions of reduced selection on either male or female
      reproduction for 40 generations in a hermaphroditic snail. This selection favors
      a reinvestment of resources from the sex function under relaxed selection toward
      the other function. We found no such evolutionary response. Instead, juvenile
      survival and male reproductive success significantly decreased in lines where
      selection on the male function (i.e., sexual selection) was relaxed, while
      relaxing selection on the female function had no effect. Our results suggest that
      most polymorphisms under selection in these lines were not sex-antagonistic.
      Rather, they were deleterious mutations affecting juvenile survival (thus
      reducing both male and female fitness) with strong pleiotropic effects on male
      success in a sexual selection context. These mutations accumulated when sexual
      selection was relaxed, which supports the idea that sexual selection in
      hermaphrodites contributes to purge the mutation load from the genome as in
      separate-sex organisms.

PMID- 30109707
TI  - Electroclinical features of epilepsy monosomy 1p36 syndrome and their
      implications.
AB  - OBJECTIVIES: Monosomy 1p36 syndrome is a recognized syndrome with multiple
      congenital anomalies; medical problems of this syndrome include developmental
      delay, facial dysmorphisms, hearing loss, short stature, brain anomalies,
      congenital heart defects. Epilepsy can be another feature but there are few data
      about the types of seizures and long term prognosis. The aim of this work was to
      analyse the electroclinical phenotype and the long-term outcome in patients with
      monosomy 1p36 syndrome and epilepsy. MATERIALS AND METHODS: Data of 22 patients
      with monosomy 1p36 syndrome and epilepsy were reconstructed by reviewing medical
      records. For each patient we analysed age at time of diagnosis, first signs of
      the syndrome, age at seizure onset, seizure type and its frequency, EEG and
      neuroimaging findings, the response to antiepileptic drugs treatment and clinical
      outcome up to the last follow-up assessment. RESULTS: Infantile Spasm (IS)
      represents the most frequent type at epilepsy onset, which occurs in 36.4% of
      children, and a half of these were associated with hypsarrhythmic
      electroencephalogram. All patients with IS had persistence of seizures, unlike
      other patients with different seizures onset. Children with abnormal brain
      neuroimaging have a greater chance to develop pharmacoresistant epilepsy.
      CONCLUSION: This syndrome represents a significant cause of IS: these patients,
      who develop IS, can suffer from pharmacoresistent epilepsy, that is more frequent
      in children with brain abnormalities.

PMID- 30109708
TI  - Health benefits of an adverse events reporting system for chronic pain patients
      using long-term opioids.
AB  - BACKGROUND: Safety data from long-term opioid therapy in the real world has been
      poorly studied in chronic non-cancer pain (CNCP). The aim was to design a
      pharmacovigilance data recording system and assess whether participation in this
      recording system improves pain management, enhancing patient's health status.
      METHODS: A pharmacovigilance data recording system was conducted during 24
      months. Data were self-reported by patients (pain, adverse events [AEs] and
      healthcare resources use) and physicians (morphine equivalent daily dose [MEDD]
      prescribed and suspected adverse drug reaction [ADRs]). Outcomes from patients
      with (case) or without (controls) suspected ADRs and cases follow-up were also
      compared with Spanish Pharmacovigilance System data. RESULTS: A total of 753
      patients were recruited in 897 visits. Fentanyl and tramadol were the most
      prescribed opioids, 89% with concomitant drugs, pregabalin being the one with the
      most potential drug interactions. Cases presented significantly higher pain
      intensity (VAS 67 +/- 26 vs 59 +/- 30 mm, P < 0.05), number of AEs (8 +/- 6 vs 5
      +/- 3 AEs/patient, P < 0.01), polypharmacy related to pain (65% vs 34%, P < 0.01)
      and MEDD (139 +/- 130 vs 106 +/- 99 mg/d, P < 0.01) than controls. Furthermore,
      cases presented significant higher changes in pharmacological pain therapy due to
      pain, unplanned emergency visits and hospital admission than controls. Physicians
      notified 168 suspected ADRs mostly related to neurological or psychiatric events
      and 8% of them were previously unknown. CONCLUSIONS: This data recording system
      provided important information to achieve a better control of CNCP
      pharmacological pain therapy, improving patient's health status and reducing
      costs to the Health System.

PMID- 30109709
TI  - Development of a simple HPLC-DAD multi-analyte procedure and its application in
      cases evaluated by the Poison Control Center of Sao Paulo, Brazil.
AB  - This work describes a simple approach to overcome challenges in emergency
      toxicological analysis, using liquid-liquid extraction and high-performance
      liquid chromatography coupled with a diode-array detector (HPLC-DAD). A rapid
      procedure has been developed, for the extraction and detection of 19 analytes
      from the following drug classes: analgesics, benzodiazepines, antidepressants,
      anticonvulsants and drugs of abuse. These substances are relevant in the context
      of emergency toxicology in Brazil. The method has been validated according to
      international guidelines by establishing parameters such as lower limit of
      quantification, sensitivity, linearity, accuracy and precision. The intra and
      inter-day precision values, at the lowest concentration levels, have always been
      less than 20% considering its relative standard deviation. As for accuracy
      values, these have also been satisfactory (above 81.3%). This method was
      successfully applied in 201 blood samples from patients with suspected poisoning
      of the Poison Control Center of Sao Paulo (PCC-SP), Brazil. Finally, the
      developed method has shown to be relevant for emergency toxicology due to its
      high sensitivity and it could be also very useful in both fields of clinical and
      forensic toxicology.

PMID- 30109711
TI  - Are guidelines for measurement of quality of life contrary to patient-centred
      care?
AB  - AIMS: A discussion of how quality-adjusted life years are used to inform resource
      allocation decisions and highlight how assumptions underpinning the measurement
      of quality of life are contrary to the principles of patient-centred care.
      BACKGROUND: Cost-effectiveness analyses (CEAs) can provide influential guidance
      for health resource allocation, particularly in the context of a budget
      constrained public health insurance plan. Most national economic guideline bodies
      recommend that quality-adjusted life year weights for CEA be elicited indirectly
      (public preferences). This has potentially important implications for healthcare
      provision and research, as it discounts the ability of a person experiencing an
      illness to describe how it affects their quality of life. DESIGN: Discussion
      paper. DATA SOURCES: Guidelines for the conduct of health economic evaluations,
      influential methodological and theoretical texts, and a review of PubMed
      conducted in April 2017. IMPLICATIONS FOR NURSING: Nurses are increasingly
      interested in leveraging methods from health economics to aid in decision-making
      and advocacy. In this analysis, we highlight how taken-for-granted approaches to
      the measurement of quality of life may discount the experience of patients and
      lead to decisions that are contrary to the principles of patient-centred care.
      Nurses conducting or reading research using these methods should consider whether
      the approach used to measure the quality of life are appropriate for the
      population under consideration. CONCLUSION: Since patient and public health
      preferences can differ in both magnitude and direction, guideline bodies should
      re-evaluate their partiality for public preferences in the reference case.

PMID- 30109712
TI  - Preparation of a radiolabeled GnRH-I analogue derivative with 111 In as a new
      anti-proliferative agent.
AB  - The new GnRH-Iotaanalogue developed in this paper was based on the D-Trp6 -GnRH
      Iota-scaffold, and its potency was increased by the replacement Gly-NH2 by NH-NH2
      binding to the Gly at position 10. Triptorelin-Hydrazide analogue was synthesized
      using solid phase. For 111 In labeling, synthesized peptide was followed by
      conjugation with DOTA using pSCN-Bn-DOTA. The conjugated Triptorelin-Hydrazide
      was labeled with 500-550 MBq of 111 In-chloride (in 0.2 M HCl). At optimized
      conditions after labeling, radio-chromatography showed radiochemical purity of
      approximately equal to 98% (RTLC) and greater than 95% (HPLC). The serum
      stability of the tracer was determined up to 24 hr. Binding affinities of
      Triptorelin-Hydrazide analogue were determined in a binding assay for both human
      and rat GnRH receptors. For in vivo studies, 111 In-peptide was injected
      intravenously via the tail vein into rats and significant ovaries uptake consist
      with reported GnRH receptor mappings. In vitro radioligand binding assays
      performed with GnRHR-expressing human cell lines using 125 I-Triptorelin as the
      standard radioligand. The quantities of internalization efficiency and receptor
      affinity of the new radioligand were IC50  = 0.20 +/- 0.04 nM vs 0.13 +/- 0.08 nM
      for Triptorelin and internalization: 3.5 +/- 0.9% at 1 hr and 12.8 +/- 1.8% at 4
      hr of the internal reference.

PMID- 30109710
TI  - Genetic dissection of bull fertility in US Jersey dairy cattle.
AB  - The service sire has been recognized as an important factor affecting herd
      fertility in dairy cattle. Recent studies suggest that genetic factors explain
      part of the difference in fertility among Holstein sires. The main objective of
      this study was to dissect the genetic architecture of sire fertility in US Jersey
      cattle. The dataset included 1.5 K Jersey bulls with sire conception rate (SCR)
      records and 96 K single nucleotide polymorphism (SNP) markers spanning the whole
      genome. The analysis included whole-genome scans for both additive and non
      additive effects and subsequent functional enrichment analyses using KEGG
      Pathway, Gene Ontology (GO) and Medical Subject Headings (MeSH) databases. Ten
      genomic regions located on eight different chromosomes explained more than 0.5%
      of the additive genetic variance for SCR. These regions harbor genes, such as
      PKDREJ, EPB41L2, PDGFD, STX2, SLC25A20 and IP6K1, that are directly implicated in
      testis development and spermatogenesis, sperm motility and the acrosome reaction.
      In addition, the genomic scan for non-additive effects identified two regions on
      BTA11 and BTA25 with marked recessive effects. These regions harbor three genes
      FER1L5, CNNM4 and DNAH3-with known roles in sperm biology. Moreover, the gene-set
      analysis revealed terms associated with calcium regulation and signaling,
      membrane fusion, sperm cell energy metabolism, GTPase activity and MAPK
      signaling. These gene sets are directly implicated in sperm physiology and male
      fertility. Overall, this integrative genomic study unravels genetic variants and
      pathways affecting Jersey bull fertility. These findings may contribute to the
      development of novel genomic strategies for improving sire fertility in Jersey
      cattle.

PMID- 30109713
TI  - Efficiency and robustness of causal effect estimators when noncompliance is
      measured with error.
AB  - Estimating causal effects from randomized controlled trials is often complicated
      due to participant noncompliance to randomized treatment. Although there are a
      variety of methods to estimate causal effects in the presence of noncompliance,
      they generally make the assumption that noncompliance is measured without error.
      This is frequently an untenable assumption, particularly when noncompliance is
      based on participant self-report. To overcome this issue, we treat compliance as
      an unobserved variable and show how to estimate the probability of compliance
      given a biomarker of treatment and the other observed data. We present inverse
      probability weighted estimators, regression-based estimators, and a doubly-robust
      augmented estimator that rely on the estimated probability of compliance rather
      than an indicator of compliance. We investigate the finite-sample properties of
      the estimators and their efficiency and robustness under correctly specified or
      misspecified models, and we apply the estimators to a recently completed trial of
      very low nicotine content cigarettes.

PMID- 30109714
TI  - Symptom clustering in patients with childhood-onset systemic lupus erythematosus.
AB  - AIMS: To: (a) explore the prevalence of the symptoms perceived by patients with
      childhood-onset systemic lupus erythematosus; (b) identify the symptom clusters
      occurring in patients with childhood-onset Systemic lupus erythematosus; and (c)
      examine the association of the burden of each symptom cluster with sleep quality
      and depression. BACKGROUND: Systemic lupus erythematosus is an inflammatory
      autoimmune disease that may result in patients' perception of various symptoms,
      with possible negative effects on their quality of life. Understanding the
      prevalence of symptoms perceived by childhood-onset Systemic lupus erythematosus
      patients and the disease's symptom clusters may be helpful in managing such
      burdensome symptoms. DESIGN: A correlational study design was used for this study
      in 2016. METHODS: Self-reported data from the Systemic lupus erythematosus
      symptom checklist were used to assess the symptoms perceived by patients. Symptom
      clusters were analysed using cluster analysis. RESULTS: Seventy-five patients
      were included in this study. The most prevalent and burdensome symptom perceived
      by patients was fatigue. Five clusters were derived, including symptoms related
      to pain and itching; bruises and stomach complaints; weight gain; body image and
      circulatory problems; and fatigue. A poor sleeper may perceive a greater symptom
      burden in all five of the symptom clusters, except for cluster #3, which refers
      to symptoms related to weight gain. CONCLUSION: Five symptom clusters were
      identified. It is hoped that this study will give useful knowledge for
      understanding the symptom clusters for patients with Systemic lupus erythematosus
      and for improving nursing care quality.

PMID- 30109715
TI  - Is there still a role for mechanical aortic valve prostheses in the TAVR era?

PMID- 30109716
TI  - Simultaneous ultraperformance liquid chromatography/tandem mass spectrometry
      determination of four antihypertensive drugs in human plasma using hydrophilic
      lipophilic balanced reversed-phase sorbents sample preparation protocol.
AB  - Therapeutic drug monitoring of angiotensin-converting enzyme inhibitors has a
      great impact on blood pressure control in patients with heart failure and hepatic
      and renal impairment. To provide an efficient tool for drug assessment in plasma,
      a UPLC-MS/MS method was developed for simultaneous determination of benazepril
      hydrochloride, fosinopril sodium, captopril and hydrochlorothiazide in human
      plasma samples. Solid phase extraction was applied for sample preparation using
      OASIS(r) hydrophilic-lipophilic balanced reversed-phase sorbents cartridges.
      Chromatographic separation was performed using an Agilent SB-C18 column and
      methanol-0.1% formic acid in water (95:5, v/v) as mobile phase, at flow rate 0.3
      mL/min. Detection was accomplished using a tandem mass spectrometer. The method
      was validated according to US Food and Drug Administration guidelines. It showed
      good linearity over concentration ranges 5-400 ng/mL for benazepril
      hydrochloride, fosinopril sodium and hydrochlorothiazide and 100-3500 ng/mL for
      captopril. CV% values were <13.92% whereas the mean accuracy ranged from 94.50 to
      113.82% for quality control samples and their extraction recoveries ranged from
      90.60 to 99.38%. In conclusion, the present study revealed method selectivity and
      sensitivity; it can be applied for estimation of angiotensin converting enzyme
      inhibitors and hydrochlorothiazide in human plasma for dose adjustment and
      therapeutic drug monitoring.

PMID- 30109717
TI  - Exploring patients' and healthcare professionals' experiences of patient
      witnessed resuscitation: A qualitative study protocol.
AB  - AIM: The aim of this study was to explore the experiences of patients and
      healthcare professionals regarding patients witnessing resuscitation on another
      patient in hospital clinical wards. DESIGN: Phenomenological qualitative study.
      METHODS: Participants will be recruited from nine wards in a university hospital
      in England. Data collection will include two in-depth interviews with patients
      who witnessed resuscitation: the first interview one week after witnessing
      resuscitation and the second interview after one month. Individual and focus
      group interviews with healthcare professionals will be also conducted. Data will
      be transcribed, managed in NVivo 11 and analysed using phenomenological analysis.
      The National Health Service, Health Research Authority and University Ethics
      Committee approved the study (May 2018). The study is funded by Resuscitation
      Council UK (December 2017) and will be conducted between May 2018-March 2019.
      CONCLUSION: While witnessed resuscitation is a major topic of interest in
      nursing, specific research on the impact of patients who witness resuscitation on
      fellow patients is limited. This study will use qualitative methodology to inform
      the evidence base of a clinical problem with limited understanding. The findings
      of this study will contribute to the framework of witnessed resuscitation and to
      identifying the barriers and enablers towards a greater support of patients who
      witness resuscitation in hospital. This new acquired knowledge will be beneficial
      to the improvement of future nursing care. IMPACT: The evidence gained from this
      study can support the development and implementation of guidelines and inform
      hospital policies to support patients witnessing resuscitation to optimize the
      quality of nursing care provided.

PMID- 30109718
TI  - Incorporation of frailties into a cure rate regression model and its diagnostics
      and application to melanoma data.
AB  - Cure rate models have been widely studied to analyze time-to-event data with a
      cured fraction of patients. Our proposal consists of incorporating frailty into a
      cure rate model, as an alternative to the existing models to describe this type
      of data, based on the Birnbaum-Saunders distribution. Such a distribution has
      theoretical arguments to model medical data and has shown empirically to be a
      good option for their analysis. An advantage of the proposed model is the
      possibility to jointly consider the heterogeneity among patients by their
      frailties and the presence of a cured fraction of them. In addition, the number
      of competing causes is described by the negative binomial distribution, which
      absorbs several particular cases. We consider likelihood-based methods to
      estimate the model parameters and to derive influence diagnostics for this model.
      We assess local influence on the parameter estimates under different perturbation
      schemes. Deriving diagnostic tools is needed in all statistical modeling, which
      is another novel aspect of our proposal. Numerical evaluation of the considered
      model is performed by Monte Carlo simulations and by an illustration with
      melanoma data, both of which show its good performance and its potential
      applications. Particularly, the illustration confirms the importance of
      statistical diagnostics in the modeling.

PMID- 30109719
TI  - Nursing Organizations' Health Policy Content on Facebook and Twitter Preceding
      the 2016 United States Presidential Election.
AB  - AIM: The aim of this study was to describe and analyse Facebook and Twitter
      content associated with three United States national nursing organizations during
      the month preceding the 2016 United States presidential election. BACKGROUND:
      Social media is increasingly significant in political and civil society dialogue.
      Many professional nursing organizations have an explicit commitment to advancing
      health policy and have established a presence on social media platforms; yet,
      little is known about what policy topics professional nursing organizations
      choose to disseminate. DESIGN: Descriptive study of qualitative data from three
      national nursing organizations' social media posts 1 month prior to the 2016
      United States presidential election. METHODS: Content analysis of social media
      content was guided by the Conceptual Module of Nursing and Health Policy and the
      Culture of Health Action Framework. RESULTS: A total of 2,137 social media units
      were collected. National Nurses United shared more policy-related content on
      Facebook and Twitter than the American Nurses Association and the American
      Academy of Nursing. Two policy issues relevant in the 2016 national election
      expanded use and regulation of marijuana and containing the cost of prescription
      drugs-received considerable attention on the nursing organizations' social media
      feeds, while a substantial percentage of analysed content was not related to
      health policy. CONCLUSION: Professional nursing organizations often represent the
      voice of nurses in policy discussions. Organization leaders and members should
      consider how social media content could enhance nurses' policy participation and
      advance dialogue about health and well-being in the context of high-stakes
      healthcare debates.

PMID- 30109720
TI  - The fear of needles: A systematic review and meta-analysis.
AB  - AIMS: The aim of this study was to evaluate the prevalence of needle fear and
      summarize the characteristics of individuals who exhibit this fear. BACKGROUND:
      Injections are among the most common medical procedures, yet fear of needles can
      result in avoidance of preventive measures and treatment. DESIGN: Systematic
      review and meta-analysis. DATA SOURCES: MEDLINE (1966-2017), Embase (1947-2017),
      PsycINFO (1967-2017), and CINAHL (1961-2017) were searched, with no restrictions
      by age, gender, race, language, or country. REVIEW METHODS: The prevalence of
      needle fear was calculated and restricted maximum likelihood random effects
      models were used for meta-analysis and meta-regression. RESULTS: The search
      yielded 119 original research articles which are included in this review, of
      which 35 contained sufficient information for meta-analysis. The majority of
      children exhibited needle fear, while prevalence estimates for needle fear ranged
      from 20-50% in adolescents and 20-30% in young adults. In general, needle fear
      decreased with increasing age. Both needle fear and needle phobia were more
      prevalent in females than males. Avoidance of influenza vaccination because of
      needle fear occurred in 16% of adult patients, 27% of hospital employees, 18% of
      workers at long-term care facilities, and 8% of healthcare workers at hospitals.
      Needle fear was common when undergoing venipuncture, blood donation, and in those
      with chronic conditions requiring injection. CONCLUSIONS: Fear of needles is
      common in patients requiring preventive care and in those undergoing treatment.
      Greater attention should be directed to interventions which alleviate fear in
      high-risk groups.

PMID- 30109721
TI  - A qualitative evaluation of the STOMA psychosocial intervention programme for
      colorectal cancer patients with stoma.
AB  - AIMS: To explore the experiences of patients who underwent a Support
      availability, Thinking positively with acceptance, Overcoming social stigma,
      Minimizing negative feelings, Analyzing self-efficacy in stoma care (STOMA)
      psychosocial intervention programme for people with colorectal cancer with stoma.
      BACKGROUND: The STOMA psychosocial intervention programme was developed to
      improve stoma-related health outcomes for patients with colorectal cancer and
      stoma. Evaluation was carried out to explore their experiences. DESIGN: A
      qualitative exploratory approach was adopted. METHODS: A total of 13 people with
      colorectal cancer, who were: (a) scheduled for surgery that resulted in a
      surgical formation of stoma at a tertiary public hospital in Singapore, and (b)
      were allocated to the intervention group and received the STOMA psychosocial
      intervention programme, were recruited for the qualitative evaluation study
      (September to November 2016). Participants were asked to comment on the contents
      and delivery methods of the intervention, and the effect of the presence of
      family members during the sessions. Thematic analysis was used to analyse the
      data. FINDINGS: Four themes were generated: (a) individual attitudes towards
      stoma, (b) benefits of the STOMA psychosocial intervention programme, (c)
      strengths of the STOMA psychosocial intervention programme, and (d)
      recommendations for future programmes. CONCLUSION: The qualitative evaluation
      reflected the benefits of the intervention programme in improving the outcome of
      people with colorectal cancer with stoma with its multimodal and multidimensional
      approach. TRIAL REGISTRATION NUMBER: ISRCTN41915584.

PMID- 30109722
TI  - Effectiveness of reflexology on anxiety of patients undergoing cardiovascular
      interventional procedures: A systematic review and meta-analysis of randomized
      controlled trials.
AB  - AIM: To appraise the evidence concerning the effect of reflexology on the anxiety
      in patients undergoing cardiovascular interventional procedures. BACKGROUND:
      Anxiety, fear, and other unpleasant emotional experiences are common among
      patients before and after cardiovascular interventional procedures. The higher
      anxiety may affect prognosis and recovery of patients. DESIGN: A systematic
      review and meta-analysis. DATA SOURCES: The MEDLINE, CINAHL (Cumulative Index to
      Nursing and Allied Health Literature), Cochrane Central Register of Controlled
      Trials (Cochrane Library), EMBASE, PsycINFO, and Web of Science were searched
      between 2001-2017. REVIEW METHODS: Randomized controlled trials evaluated the
      effectiveness of reflexology on anxiety among patients undergoing cardiovascular
      interventional procedures were included. Meta-analysis was done using Revman 5.3.
      RESULTS: Ten trials, representing 760 patients with the mean age of 59, fulfilled
      the inclusion criteria. Reflexology significantly decreased the anxiety of
      patients undergoing cardiovascular interventional procedures in the treatment
      group compared with the control group. CONCLUSION: Reflexology has some positive
      effects on anxiety among patients undergoing cardiovascular procedures. It may be
      a useful complementary therapy and further research is necessary to create
      reliable evidence.

PMID- 30109723
TI  - A longitudinal investigation of trust beliefs in physicians by children with
      asthma and their mothers: Relations with children's adherence to medical regimes
      and quality of life.
AB  - OBJECTIVE: The study examined the relations between trust beliefs in physicians,
      adherence to prescribed medical regimes, and quality of life for children with
      asthma and their mothers. METHODS: One hundred forty-three children with asthma
      (116 males, M = 12 years-7 months) and their mothers were tested twice (Time 1/T1
      and Time 2/T2) across a 1-year period. Standardized measures were administered
      that assessed the children's and mothers' trust beliefs in physicians, the
      children's quality of life, and children's adherence to prescribed medical
      regimes (adherence). RESULTS: Correlations were found between children's trust
      beliefs in physicians, mothers' trust beliefs in physicians, adherence, and
      quality of life. Structural equation modelling analyses confirmed that (a)
      children's trust beliefs in physicians predicted their adherence and quality of
      life and (b) there were reciprocal predictive relations between the children's
      and mothers' trust beliefs in physicians. CONCLUSIONS: The findings yield support
      for the conclusions that (a) trust beliefs in physicians by children with asthma
      promote their adherence and quality of life and (b) socialization of trust
      beliefs in physicians is a mutual mother-child process.

PMID- 30109724
TI  - Supportive clinical supervision: Supported at last.

PMID- 30109725
TI  - Implementation and evaluation of an education programme for nursing staff on
      recognising, reporting and managing resident-to-resident elder mistreatment in
      aged care facilities.
AB  - AIM: To implement an educational programme for nursing staff on recognising,
      reporting and managing resident-to-resident elder mistreatment in aged care
      facilities. BACKGROUND: The phenomenon of a growing ageing population increases
      the demand of optimum care for older people living in aged care facilities.
      Caring for older people is complex, but should include the management of
      aggressive interaction between them. Nursing staff play a vital role in
      identifying and managing those behaviours. However, many nurses may not recognise
      these aggressive interactions as abuse. Therefore, this study aims to manage and
      reduce this abuse through an educational programme. DESIGN: Cluster randomised
      trial registered on the Australia New Zealand Clinical Trial Registry (ACTRN
      12617001618347). METHODS: This trial was undertaken in an aged care facility
      located in Melbourne, Australia and was funded in January 2017. Wards were
      randomly allocated (as the intervention and control group) by using sealed opaque
      envelopes. Nursing staff, who met eligibility, were consecutively recruited and
      supplied their informed consent. Nurses from the intervention group received an
      educational programme, while nurses from the control group continued with the
      usual standard care. Main outcomes included recognising, managing and reporting
      the abuse before and after the intervention and will be evaluated on an intention
      to-treat analysis. DISCUSSION: It is vital to manage and reduce resident-to
      resident elder mistreatment. This educational programme may assist nursing staff
      to protect vulnerable older people experiencing this abuse and may improve
      comprehensive evidence-based care for older people residing in aged care
      facilities.

PMID- 30109726
TI  - Between inflammation and melanoma: The 4th ADF Round Table.

PMID- 30109727
TI  - What are the beliefs and perceptions of practice nurses' influence about the
      uptake of the measles, mumps, and rubella vaccine?: An integrative literature
      review.
AB  - AIM: The aim of this study was to ascertain the beliefs and perceptions of
      practice nurses' influence about the uptake of the measles, mumps, and rubella
      vaccine. BACKGROUND: Immunization decision-making for parents is a complex
      process. Principle health professionals involved in immunization programmes are
      health visitors, general practitioners, and practice nurses. There is evidence
      that health visitors and general practitioners influence parental immunization
      decision-making. However, there is a lack of evidence about the influence of the
      practice nurse despite their well-documented role in immunization. DESIGN:
      Integrative literature review. DATA SOURCES: A systematic search of electronic
      databases, including CINAHL; Medline; PubMed; Google Scholar; ScienceDirect; and
      Scopus from February 1998 - April 2017. Hand searching and reviewing of secondary
      references were also undertaken. REVIEW METHODS: Two reviewers independently
      screened records on title and abstract. Studies where the beliefs and perceptions
      of practice nurses about the measles, mumps, and rubella vaccine were explored
      and were published in English were included. The data were analysed using the
      integrative review processes. RESULTS: Twelve studies were included; these
      studies were principally descriptive and were of variable methodological quality.
      Four themes were identified: parental immunization influencing factors, practice
      nurse characteristics, information and communication, and personal views and
      concerns. While this review provides an excellent baseline for this information,
      more recent research conducted in the current policy environment is urgently
      needed to determine if these views persist. CONCLUSION: Immunization training and
      annual updates are essential for practice nurses to keep abreast with the
      evidence base underpinning national immunization programmes.

PMID- 30109728
TI  - A theory-based hybrid II implementation intervention to improve pain management
      in Swiss nursing homes: A mixed-methods study protocol.
AB  - AIM: To present a protocol for evaluating an implementation intervention to
      improve pain management in nursing homes by addressing behaviour change of the
      care workers. BACKGROUND: Pain management in nursing homes often is inadequate
      despite the availability of evidence-based pain management guidelines. Barriers
      to pain management in nursing homes occur on several levels including lack of
      knowledge and negative beliefs towards pain of care workers. A comprehensive
      approach incorporating contextual and behavioural factors is needed to
      sustainably improve pain management practice. DESIGN: A hybrid type II
      effectiveness-implementation design comprising an incomplete non-randomized
      stepped-wedge design and concurrent focus groups is proposed. METHODS: A
      convenience sample of six nursing homes will be included. Implementation of a
      facility pain management policy will be facilitated by introduction of a facility
      pain champion and training of all care workers in pain assessment and management.
      Quantitative outcomes assessed at baseline, after 3 and 6 months include self
      efficacy in pain management and attitudes to pain of care workers and functional
      interference from pain and pain intensity in residents. Feasibility and
      acceptability of the intervention and implementation strategies and potential
      barriers to implementation will be explored in focus groups and interviews.
      (Protocol approved in October 2017). CONCLUSION: The proposed intervention
      implementation has been developed in a participatory approach involving relevant
      stakeholders. To further improve the contextual fit, development of
      implementation strategies was guided by the consolidated framework of
      implementation research. Findings of this research are expected to inform
      adaptions to the implementation of the intervention. TRIAL REGISTRATION NUMBER:
      ClinicalTrials.gov: NCT03471390.

PMID- 30109729
TI  - Compound Words Reflect Cross-Culturally Shared Bodily Metaphors.
AB  - Parts of the body are often embedded in the structure of compound words, such as
      heartbreak and brainchild. We explored the relationships between the semantics of
      compounds and their constituent body parts, asking whether these relationships
      are largely arbitrary or instead reflect deeper metaphorical mappings shared
      across languages and cultures. In three studies, we found that U.S. English
      speakers associated the English translation equivalents of Chinese compounds with
      their constituent body parts at rates well above chance, even for compounds with
      highly abstract meanings and even when accounting for the semantic relatedness of
      the compounds and body parts. English speakers in India and Chinese speakers in
      Hong Kong showed similar intuitions about these associations. Our results suggest
      that the structure of compound words can provide insight into cross-culturally
      shared ways of connecting meaning to the body.

PMID- 30109730
TI  - Individualization process of the standardized care plan in acute care
      hospitalization units: Study protocol.
AB  - AIM: To understand the individualization process of the standardized care plan
      (SCP) that nurses design for hospitalized patients. BACKGROUND: To apply the
      nursing process, it is advisable to use SCP to standardize the diagnosis,
      planning and evaluation stages. However, the fundamental element of this
      methodology is the individualization of the care plan. DESIGN: A qualitative
      study, framed within the constructivist paradigm and applying the Grounded Theory
      method, in accordance with Strauss and Corbin's approach. METHODS: Multicentre
      study. Theoretical sampling with maximum variation will be used. The data
      collection will consist of: in-depth individual interviews, participant
      observation, document analysis, focus group, and the questionnaires for Critical
      Thinking Assessment in relation to clinical practice and Nursing Competency
      Assessment for hospital nurses. The qualitative data will be analysed according
      to the constant comparative method of Strauss and Corbin's Grounded Theory, which
      involves performing open, axial and selective coding. The questionnaire results
      will be used to make a qualitative analysis that will consist of a triangulation
      between the level of critical thinking, level of expertise and record of the
      individualization process performed by the nurses. This protocol was approved in
      July 2015. DISCUSSION: By knowing the possible stages used in the
      individualization of a SCP, together with the elements that facilitate or hinder
      said individualization and nurses' attitudes and experiences regarding this
      phenomenon, it could help direct improvement strategies in the standardization
      and individualization process. In addition to recommendations for teaching and
      research.

PMID- 30109731
TI  - Design of experiments for the optimization of electrospray ionization in the LC
      MS/MS analysis of ciguatoxins.
AB  - Liquid chromatography (LC) coupled to mass spectrometry (MS) is being widely
      applied as an analytical tool in the field of marine biotoxins both for regulated
      and for new and emerging compounds. LC-MS/MS recently became the reference method
      for the control of lipophilic toxins in the European Union, and new methods are
      being developed and optimized to extend the applicability of this technique to
      other toxin groups. In this work, conditions for the analysis of ciguatoxins
      (CTXs) by LC-MS/MS were investigated using standard solutions of CTX1B and CTX3C,
      which are structurally representative compounds for the rest of the main
      congeners of Pacific group toxins (P-CTXs). Preliminary studies were carried out
      for the selection of precursor and product ions used for multiple reaction
      monitoring. Two transitions based on the chemical structures of CTXs were set up,
      and mass spectrometer parameters were adjusted for selected reactions monitored.
      The electrospray ionization source has been carefully optimized through a design
      of experiments that consisted of a two-level fractional factorial design of
      resolution IV for the screening of adequate source conditions and of response
      surface designs for optimization of the main interactions between factors. The
      statistical approach allowed maximizing the sensitivity on the MS analyzer that
      provides a good specificity in P-CTX detection, which can be also used for
      confirmation purposes.

PMID- 30109732
TI  - How do new molecular tools apply to my clinical practice?

PMID- 30109733
TI  - Clinical and histopathological features of Burkholderia cepacia complex
      dermatitis in dogs: a series of four cases.
AB  - BACKGROUND: The Burkholderia cepacia complex (Bcc) is an emerging cause of
      opportunistic infections. Deep pyoderma associated with Bcc infection has been
      reported previously in dogs receiving ciclosporin. OBJECTIVE: To report the
      clinical and histopathological features of four additional cases of Bcc
      dermatitis in dogs, one of which progressed to septicaemia. ANIMALS: Four dogs
      with a skin culture yielding growth of Bcc and skin biopsies for
      histopathological investigation. METHODS AND MATERIALS: Retrospective review of
      medical records and skin biopsies and PCR for Burkholderia on DNA extracted from
      paraffin-embedded skin and liver to confirm Bcc sepsis. RESULTS: Three different
      breeds and one mixed breed dog were represented. Two dogs were receiving
      ciclosporin and one was receiving oclacitinib. One dog had no evidence of
      immunosuppression. One dog was bathed two days prior to onset of skin lesions.
      Three dogs presented with dorsally orientated ulcers, crusts and draining tracts;
      one dog had infection localized to a surgical site. The main histological feature
      from skin biopsies was severe neutrophilic folliculitis and furunculosis with
      marked neutrophilic to pyogranulomatous dermatitis. Intracellular Gram-negative
      and Warthin-Starry positive rods were present in three of four cases. Three dogs
      were successfully treated with systemic fluoroquinolones or trimethoprim
      sulfamethoxazole. The Bcc isolate in one dog was resistant to all tested systemic
      antimicrobials. This dog developed septicaemia and was euthanized. CONCLUSIONS
      AND CLINICAL IMPORTANCE: Bcc skin infections can occur in immunocompetent and
      immunocompromised dogs. Bcc isolates may be extensively antimicrobial resistant,
      presenting a challenge for clinical management. Cutaneous infection may progress
      to life-threatening sepsis.

PMID- 30109734
TI  - Polymorphisms in TH1-TH2 cytokine and receptor genes associated with risk of
      vertical HIV transmission, in Mumbai, India.
AB  - BACKGROUND: Vertical HIV transmission does not occur in all exposed infants. Many
      infants remain HIV uninfected even after exposure. This is partly attributed to
      the host genes involving cytokine production, which is rarely documented in
      vertical transmission. METHODS: Here, an observational cohort study evaluated
      whether polymorphisms in cytokine, receptor and antagonist genes are associated
      with perinatal HIV transmission. Single nucleotide polymorphism (SNP) genotyping
      was performed via the polymerase chain reaction with sequence-specific primers
      method. Haplotype block structure was determined and statistical analysis was
      performed using appropriate software in each case. RESULTS: Twenty-two SNPs were
      analysed in 30 seropositive and 61 seronegative children. Confounding factors
      such as mother's viral load, treatment regimen, breast feeding options, etc.,
      were documented. Analysis revealed the association of two SNPs: IL1R1 (rs2234650)
      and TNFA (rs1800629) with vertical HIV transmission. CT genotype at IL1R1 was
      observed at a higher frequency in positive children (76.66% versus 42.62%, p =
      0.002), whereas the CC genotype was significantly increased in exposed uninfected
      children (47.54% versus 16.66%, p = 0.004). Similarly, the GG genotype of TNFA
      was significantly higher in uninfected children compared to infected ones (76.66%
      versus 46.66%, p = 0.005), whereas the GA genotype frequency was higher among
      infected children (53.33% versus 21.66%, p = 0.003). The frequency of the 'G'
      allele of TNFA and 'C' allele of IL1R1 was significant (p = 0.018) in negative
      children. Haplotypes of SNPs belonging to IL1, TNFA and IL4 were also found to
      associate with transmission. CONCLUSIONS: The present study confirms the
      association of SNPs IL1R1 (rs2234650) and TNFA (rs1800629) with the risk of
      vertical transmission. These SNPs can be exploited as possible predictive markers
      of HIV transmission.

PMID- 30109735
TI  - Short-medium-long-term efficacy of interdisciplinary intervention against
      overweight and obesity: Randomized controlled clinical trial.
AB  - AIM: The aim of the study is to evaluate the efficacy of a nurse-led
      interdisciplinary programme based on healthy eating, physical exercise, and
      cognitive behavioural therapy applied to anthropometric and cardiovascular
      measures, which are related to obesity in short, medium, and long term. METHODS:
      We conducted a randomised controlled clinical trial with 74 obese and overweight
      participants (experimental group, n = 37; control group, n = 37). An
      interdisciplinary programme of 12 months was applied and coordinated by a nurse.
      Anthropometric and cardiovascular measures were taken at the pretest stage, every
      6 months during the programme, and 1 year after it finished. RESULTS: A
      beneficial effect was found regarding all anthropometric parameters. Tests for
      weight (F3;207  = 93.27; P < .001) and body mass index (F3;207  = 89.95; P <
      .001) indicate efficacy of intervention: The experimental group had a weight loss
      of 7.2 kg (-8.3%) compared to a 0.9 kg (+1.0%) gained in the control group.
      Systolic (F3;207  = 37.06; P < .001) and diastolic (F3;216  = 57.31; P < .001)
      blood pressure improved greatly in the experimental group. Forced vital capacity
      was also increased (F2;138  = 15.51; P < .001). CONCLUSION: The interdisciplinary
      programme coordinated by nurses improved the health of participants, maintaining
      long-term effects.

PMID- 30109736
TI  - 3D Microstructured Scaffolds to Support Photoreceptor Polarization and
      Maturation.
AB  - Blinding disorders of the outer retina involve dysfunction and degeneration of
      photoreceptors. One potential approach to treat these forms of blindness is to
      repopulate the outer retina via a simple bolus injection of donor photoreceptors.
      However, this may not be ideal due to the highly polarized organization of
      photoreceptors that include apical light sensing photopigments and basal axon
      terminals. Furthermore, bolus injections create uncertainty with regard to the
      area, density, and retention of donor cells. Here, a novel and robust
      microfabrication process is developed to create 3D, micrometer-sized complex
      structures in ultrathin and biocompatible elastomer films (nonbiodegradable
      polydimethylsiloxane and biodegradable poly(glycerol-sebacate)) that can serve as
      polarizable photoreceptor delivery scaffolds, consisting of an array of cup
      shaped photoreceptor capture wells that funnel into a microchannel. This "wine
      glass" scaffold design promotes efficient capture of human pluripotent stem-cell
      derived photoreceptor cell bodies and guidance of basal axon extensions,
      ultimately achieving a uniform level of organization and polarization that is not
      possible with bolus injections or previously described scaffolds. In addition to
      future therapeutic applications, our scaffold design and materials provide a
      platform to generate reproducible and scalable in vitro models of photoreceptor
      based diseases.

PMID- 30109737
TI  - Amorphous/Crystalline Hetero-Phase Pd Nanosheets: One-Pot Synthesis and Highly
      Selective Hydrogenation Reaction.
AB  - Similar to heterostructures composed of different materials, possessing unique
      properties due to the synergistic effect between different components, the
      crystal-phase heterostructures, one variety of hetero-phase structures, composed
      of different crystal phases in monometallic nanomaterials are herein developed,
      in order to explore crystal-phase-based applications. As novel hetero-phase
      structures, amorphous/crystalline heterostructures are highly desired, since they
      often exhibit unique properties, and hold promise in various applications, but
      these structures have rarely been studied in noble metals. Herein, via a one-pot
      wet-chemical method, a series of amorphous/crystalline hetero-phase Pd nanosheets
      is synthesized with different crystallinities for the catalytic 4-nitrostyrene
      hydrogenation. The chemoselectivity and activity can be fine-tuned by controlling
      the crystallinity of the as-synthesized Pd nanosheets. This work might pave the
      way to preparing various hetero-phase nanostructures for promising applications.

PMID- 30109739
TI  - Oral administration of powdered dried rhizomes of Curcuma longa L. (turmeric,
      Zingiberaceae) is effective in the treatment of doxorubicin-induced kidney injury
      in rats.
AB  - Curcumin is a polyphenol present in the rhizomes of the species Curcuma longa L.
      ("turmeric," Zingiberaceae), which has been used for centuries as an anti
      inflammatory. We aimed to evaluate the anti-inflammatory effects of C. longa in
      renal injury induced by doxorubicin (DOX, 3.5 mg.kg-1 IV). We studied four groups
      of Wistar rats: two groups with DOX-induced kidney injury, one fed with standard
      food and another with standard food mixed with C. longa (5 mg.g-1 ). Two other
      control groups without kidney injury were fed with the same foods. We measured
      albuminuria, body weight, and food intake every 2 weeks. After 8 weeks, treatment
      with C. longa did not change albuminuria, but it significantly attenuated the
      excretion of urinary inflammatory markers monocyte chemoattractant protein-1 (MCP
      1) and transforming growth factor-beta (TGF-beta) and significantly attenuated
      immunostaining for desmin, vimentin, and ED-1+ cells in renal tissues of rats
      with DOX-induced kidney injury. In addition, treatment with C. longa resulted in
      significantly lower glomerular and tubule interstitial injury scores, compared
      with that in the DOX-STD group. In conclusion, administration of powdered
      rhizomes of C. longa for 8 weeks to rats with DOX-induced kidney injury did not
      reduce albuminuria but led to a significant decrease in urinary inflammatory
      markers MCP-1 and TGF-beta and decreased histopathological alterations and
      immunostaining for desmin, vimentin, and ED-1+ cells kidneys tissues.

PMID- 30109740
TI  - RhIII -Catalyzed Functionalization of closo-Dodecaborates by Selective B-H
      Activation: Bypassing Competitive C-H Activation.
AB  - The closo-dodecaborate dianion is a fundamental icosahedral boron cage with 12
      identical B-H vertices. The chemistry and applications of boron clusters have
      inspired researchers ever since their discovery several decades ago, and the
      selective modification of the cage positions has remained a major synthetic
      challenge. A rhodium(III)-catalyzed B-H functionalization-cyclization cascade of
      closo-dodecaborate amides is reported. The transformations occur chemoselectively
      at B-H positions in the presence of C-H bonds prone to competitive
      cyclometalation. Previously inaccessible cage derivatives with B-C(sp2 ) and B
      C(sp3 ) bonds as well as a fused diboraoxazole ring are obtained in a one-pot
      process. The reactions proceed under mild conditions and exhibit complete cage
      regioselectivity with broad functional group tolerance. These cluster derivatives
      enable a largely extended investigation of the application of anionic boron
      clusters in research areas such as photoluminescent materials and medicinal
      chemistry.

PMID- 30109738
TI  - Adolescent and young adult cancer survivors' memory and future thinking processes
      place them at risk for poor mental health.
AB  - OBJECTIVE: Identity formation is a key developmental milestone for adolescents
      and young adults (AYAs). Autobiographical memory and future-thinking are crucial
      cognitive processes underpinning this, which may be impacted by cancer
      experiences. We know little about how these processes might be related to AYAs'
      adjustment to cancer, quality of life (QoL), and mental health outcomes. METHODS:
      We examined autobiographical memory and future-thinking processes, and their
      relationship with mental health outcomes, among 77 AYA cancer survivors (Mage  =
      22.3 years, 59.7% female), compared with 62 community-based controls (Mage  =
      23.3 years, 50% female). Participants completed the Life Narratives Interview,
      Future Imaginings Task, measures assessing depression, anxiety, QoL, and cancer
      related identity. We coded two facets of autobiographical thinking: thematic
      content and specificity. RESULTS: Relative to controls, survivors recounted more
      negative life narratives (P = .000). Survivors' memories and future lives were
      more health/illness-focused (P = .000) and they remembered past events with
      greater specificity (P = .007) than controls. In contrast, survivors imagined
      their future lives with less specificity than controls (P = .000). Regression
      analyses highlighted that being female, greater identification as a "cancer
      survivor," worse depression, and recent cancer treatment-completion significantly
      predicted maladaptive autobiographical thinking processes. CONCLUSIONS: These
      findings point to key modifiable cognitive processes relevant to AYAs' cancer
      related adjustment and future mental health. To bolster resilience into longer
      term survivorship, clinicians could adapt existing evidence-based, cognitive
      behavioural interventions to assist AYAs to imagine future events in greater
      detail.

PMID- 30109741
TI  - Fetal alcohol spectrum disorder in Australia: What is the current state of
      affairs?
AB  - The term fetal alcohol spectrum disorder (FASD) is used to describe a wide range
      of difficulties that individuals who are exposed to alcohol prenatally can face.
      FASD is a significant public health concern that is currently under-recognised
      and consequently, under-diagnosed in Australia. A new Commonwealth FASD Strategy
      (2018-2028) is being developed and the Australian Government has announced
      significant funding for the expansion of FASD prevention, diagnostic and
      intervention services around Australia. Therefore, it is timely to consider what
      the current state of affairs regarding FASD in Australia is and describe areas
      for future research and service delivery.

PMID- 30109742
TI  - Comparison of two ear cytological collection techniques in dogs with otitis
      externa.
AB  - BACKGROUND: Canine otitis externa is a common disease. Cytological evaluation of
      otic exudate is a useful diagnostic test to direct and monitor treatment for
      otitis externa. One method of collecting ear cytological specimens utilizes a
      cotton-tipped swab inserted into the vertical ear canal. A proposed alternative
      method is to aspirate exudate from the deep horizontal canal using a rubber tube.
      HYPOTHESIS/OBJECTIVES: To compare cytological findings between two different
      collection techniques by evaluating the numbers of bacteria, Malassezia yeast and
      inflammatory cells. ANIMALS: Thirty client-owned dogs with otitis externa.
      METHODS AND MATERIALS: A prospective, randomized, blinded comparison study. Ear
      canals from each dog were sampled using cotton swab and rubber tube. Ear
      cytological preparations were evaluated independently by two investigators for
      polymorphonuclear leucocytes (PMN), monocytes/lymphocytes, macrophages, yeast,
      intracellular (IC) cocci, extracellular (EC) cocci, IC bacilli and EC bacilli.
      RESULTS: A paired Student's t-test was used to compare the two techniques. The
      inter-investigator reliability for PMN, EC bacilli and yeast was good, and for EC
      cocci was moderate. There were significantly higher numbers of PMNs obtained by
      the tube method (P = 0.0024) than by the cotton swab method. There were no
      statistically significant differences between cotton swab and rubber tube methods
      for monocytes/lymphocytes (P = 0.7780), macrophages (P = 0.1751), EC cocci (P =
      0.1262), EC bacilli (P = 0.1162), yeast (P = 0.5371), IC cocci (P = 0.6606) or IC
      bacilli (P = 0.6761). The technique was well tolerated. CONCLUSION: An
      alternative ear cytological collection technique was identified which enables
      sampling of the deep horizontal canal.

PMID- 30109743
TI  - Current natural therapies in the treatment against glioblastoma.
AB  - Glioblastoma (GBM) is the most common and aggressive brain tumor, which causes
      the highest number of deaths worldwide. It is a highly vascularized tumor,
      infiltrative, and its tumorigenic capacity is exacerbated. All these hallmarks
      are therapeutic targets in GBM treatment, including surgical removal followed by
      radiotherapy and chemotherapy. Current therapies have not been sufficient for the
      effective patient's management, so the classic therapies have had to expand and
      incorporate new alternative treatments, including natural compounds. This review
      summarizes natural products and their physiological effects in in vitro and in
      vivo models of GBM, specifically by modulating signaling pathways involved in
      angiogenesis, cell migration/invasion, cell viability, apoptosis, and
      chemoresistance. The most important aspects of natural products and their
      derivatives were described in relation to its antitumoral effects. As a final
      result, it can be obtained that within the compounds with more evidence that
      supports or suggests its clinical use are the cannabinoids, terpenes, and
      curcumin, because many have been shown to have a significant effect in decreasing
      the progress of GBM through known mechanisms, such as chemo-sensitization or
      decrease migration and cell invasion. Natural compounds emerge as promising
      therapies to attack the progress of GBM.

PMID- 30109744
TI  - Modelling opportunity: An examination of quadratic effects of adolescent
      Venezuelan substance use.
AB  - INTRODUCTION AND AIMS: Numerous studies have found a linear relationship between
      an exposure opportunity and age of first drug use. This study further tests this
      relationship by exploring whether a quadratic exposure opportunity best fits the
      data on age of first use and whether gender moderates this relationship. That is,
      is there a peak age in which the transition to use occurs for male compared to
      female adolescents? DESIGN AND METHODS: A sample of 1716 adolescents from 14
      public and private schools, representative of two school districts in Caracas,
      Venezuela, was examined using a zero-inflated Poisson modelling approach to test
      for quadratic effects. A series of models were tested for each set of substances
      (alcohol, tobacco and other drugs) to assess whether a quadratic model has better
      predictive ability than linear models and to test whether gender moderates the
      quadratic relationship. RESULTS: After controlling for common covariates, the
      quadratic models for alcohol indicated the peak age of transition from an
      exposure opportunity to use was 10-years of age in this Venezuelan sample. Gender
      did not moderate these models suggesting an important move toward gender equality
      in substance use. DISCUSSION AND CONCLUSIONS: Focused efforts on preventing
      exposure to alcohol use during these windows of rapid transition is likely to
      have the greatest impact on delaying age of onset, which will reduce the overall
      prevalence of alcohol related problems among adolescents.

PMID- 30109746
TI  - Extremely stable high molecular mass soluble multiprotein complex from eggs of
      sea urchin Strongylocentrotus intermedius with phosphatase activity.
AB  - It was proposed that most biological processes are performed by different protein
      complexes. In contrast to individual proteins and enzymes, their complexes
      usually have other biological functions, and their formation may be important
      system process for the expansion of diversity and biological functions of
      different molecules. Identification and characterization of embryonic components
      including proteins and their multiprotein complexes seem to be very important for
      an understanding of embryo function. We have isolated and analyzed for the first
      time a very stable multiprotein complex (SPC; approximately 1100 kDa) from the
      soluble fraction of extracts of the sea urchin embryos. By fast protein liquid
      chromatography (FPLC) gel filtration the SPC was well separated from other
      extract proteins. Stable multiprotein complex is stable in different drastic
      conditions but dissociates moderately in the presence of 8M urea + 1.0M NaCl.
      According to sodium dodecyl sulfate polyacrylamide gel electrophoresis data, this
      complex contains many major, moderate and minor proteins with molecular masses
      from 10 to 95 kDa. The SPC was destroyed by 8M urea or SDS, and its components
      were separated using thin layer chromatography, ion-exchange chromatography, gel
      filtration, and reverse phase chromatography. Using matrix-assisted laser
      desorption/ionization mass spectrometry of partially dissociated SPC, it was
      shown that the complex contains not only proteins (10-95 kDa) but also few dozens
      of peptides with molecular masses from 2 to 9.5 kDa. Short peptides form very
      strong complexes, which at the treatment of SPC with urea or SDS can be partially
      break down into smaller complexes having different peptide compositions. Reverse
      phase chromatography of these complexes after all type of abovementioned
      chromatographies led to detection from 6 to 11 distinct peaks corresponding to
      new complexes containing up to a few dozens of peptides. The SPCs possess
      alkaline phosphatase activity. Progress in the study of embryos protein complexes
      can help to understand their biological functions.

PMID- 30109748
TI  - A cross-sectional study of show English bulldogs in the United States: evaluating
      paw lesions, cytological findings, pruritic behaviours and gastrointestinal
      signs.
AB  - BACKGROUND: English bulldogs (EBDs) are considered to commonly show signs of
      pododermatitis and gastrointestinal (GI) disease. HYPOTHESIS/OBJECTIVES: To
      describe a population of presumed healthy EBDs: (i) evaluate dogs according to
      published criteria for health, (ii) describe paw lesions, if present, (iii)
      report pruritic behaviours and GI signs and compare to normal values, (iv) report
      pedal cytological findings, and (v) determine correlation between lesions,
      cytological results and pruritic behaviours. ANIMALS: Thirty four EBDs
      participating in a dog show. METHODS AND MATERIALS: Dogs were examined, and pedal
      cytological samples were collected. Pruritic behaviours, GI signs and medical
      history were assessed. Owners completed questionnaires regarding history and
      assessed pruritus. RESULTS: No dog met criteria for being healthy. All dogs had
      an abnormal dermatological examination, 22 of 34 had a history of recent drug
      administration and 16 of 34 had a history of dermatological disease. Every dog
      had at least one erythematous paw. Compared to values for a healthy dog
      population, facial rubbing was the only increased pruritic behaviour, and GI
      signs differed in belching, flatulence and regurgitation. Mean cytological
      evaluation values were within normal ranges except for inflammation. Lesions did
      not correlate with cytological findings or pruritic behaviours, with the
      exception of white coloured exudation with inflammation and cocci. CONCLUSIONS
      AND CLINICAL IMPORTANCE: This study supports that show EBDs have frequent pedal
      lesions and history of dermatological disease, with over half receiving
      medication, as well as increased frequency of belching, flatulence and facial
      rubbing. Pedal cytological findings were not predictive of lesions, with the
      exception of white coloured exudation.

PMID- 30109747
TI  - Artichoke leaf extract, as AKR1B1 inhibitor, decreases sorbitol level in the rat
      eye lenses under high glucose conditions ex vivo.
AB  - In the previous study, the artichoke leaf extract showed effective inhibition of
      AKR1B1, the first enzyme of polyol pathway, which reduces high level of glucose
      to osmotically active sorbitol, important for development of chronic diabetic
      complications. In the present study, the effect of artichoke leaf extract and of
      several participating phenols (caffeic acid, chlorogenic acid, quinic acid, and
      luteolin) was tested on sorbitol level in rat lenses exposed to high glucose ex
      vivo, on cytotoxicity as well as on oxidative stress in C2C12 muscle cell line
      induced by high glucose in vitro. The concentration of sorbitol was determined by
      enzymatic analysis, the cytotoxicity was provided by WST-1 test and intracellular
      content of reactive oxygen species was determined by fluorescence of 2'-7'
      dichlorofluorescein probe. The extract and the compounds tested showed
      significant protection against toxic effects of high concentration of glucose in
      both models. On balance, the artichoke leaf extract thus represents a prospective
      preventive agent of development of chronic diabetic complications, probably due
      to phenols content, concerning preclinical and clinical studies.

PMID- 30109745
TI  - Antiinflammation constituents from Curcuma zedoaroides.
AB  - Curcuma zedoaroides, a Zingiberaceae species, has been used for snake bite
      antidote and wound care in Thailand. Seven compounds were isolated from the
      bioactive chloroform extract consisted of one new guaiane sesquiterpene lactone,
      5-epiphaeocaulisin A (4) and one new diarylheptanoid, 1,2,3,5-tetrahydroxy-1-(4
      hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl) heptane (7), together with five
      known guaiane-type sesquiterpene lactones including gweicurculactone (1),
      zedoalactone B (2), phaeocaulisin C (3), zedoalactone H (5), and zedoalactone E
      (6). The antiinflammation was investigated on NO and TNF-alpha production using
      RAW264.7 cells. In addition, the expressions of genes involved in inflammation
      including iNOS, COX-2, and TNF-alpha were assessed. The results found that
      Compounds 1-7 presented their antiinflammation against NO production. The most
      potential effects were demonstrated on Compounds 1 and 7 with IC50 of 27.3 and
      32.6 MUM, respectively. Although, Compounds 1 and 7 did not inhibit TNF-alpha
      production, their suppression on iNOS and COX-2 mRNA expression were revealed.
      These results support the ability of chloroform fraction, Compounds 1 and 7 on
      antiinflammation, whereas others exhibited moderate and mild effect.

PMID- 30109750
TI  - Effect of midwife-led care on birth outcomes of primiparas.
AB  - BACKGROUND: The high caesarean section rate is a prominent public health problem
      in China. AIM: This study aimed to determine the effects of midwife-led care
      during labour on birth outcomes for healthy primiparas. DESIGN: Randomized
      controlled trial. SETTING: The Obstetrics Department of Fujian Provincial
      Maternity and Child Health Hospital. METHODS: A total of 666 primiparas in labour
      were randomly divided into an intervention and control group (333 in each group).
      The intervention group received a midwife-led model of care during labour.
      RESULTS: Data from 648 cases (331 intervention group and 317 control group) were
      analysed. The intervention group was less likely to experience caesarean section,
      postpartum haemorrhage, opiate analgesia, vaginal examinations, neonatal
      asphyxia, and neonatal hospitalization and was more likely to experience shorter
      length of labour and vaginal birth than the control group (all, P < 0.05). No
      differences were found in the number of artificial rupture of membranes and
      oxytocin use (P > 0.05). CONCLUSIONS: Midwife-led care can reduce the caesarean
      section rate, promote normal birth, improve birth outcomes, and promote maternal
      and child health.

PMID- 30109751
TI  - Supermacrocyclic Assemblies by Hydrogen-Bond Codes of C7-Phenol Pyrazolo and
      Pyrrolo Derivatives of Adenine.
AB  - Hydrogen bond (HB) mediated base pair motifs are versatile scaffolds of diverse
      supramolecular constructs. Here, we report that two new four- and six-membered
      supermacrocyclic assemblies with intriguing geometries could self-assemble from
      two new adenine derivatives, APN (1) and APC (2). The conversion of a
      conventional HB acceptor, N8 of 1, to a non-conventional HB donor, C8-H of 2, had
      a pronounced impact on the overall intricate HB network and self-assembly
      patterns, epitomizing the subtleties in design and exploitation of such base-pair
      motifs as promising tectons for building supramolecular architectures.

PMID- 30109753
TI  - Low-Temperature Thermal Rate Constants for the Water Formation Reaction H2 +OH
      from Rigorous Quantum Dynamics Calculations.
AB  - Thermal rate constants for the prototypical water-forming reaction H2 +OH->H+H2 O
      were obtained for temperatures between 150 K and 600 K by rigorous quantum
      dynamics calculations including all degrees of freedom. Results are reported for
      a recent, highly accurate neural network potential (NN1) and compared to results
      obtained on a previous, semi-empirical potential (SE). The rate constants
      computed on both potentials significantly differ in their temperature dependence,
      and differences of over one order of magnitude in the rates were found. The rate
      constants computed for the NN1 potential compare very well to experimental work.
      Furthermore, the influence of overall rotation is discussed for the title
      reaction. While previous close-coupling simulations were limited to thermal rate
      constants above room temperature, we report rate constants for temperatures as
      low as 250 K. The high-level results reported here provide an accurate benchmark
      for the development of approximate methods for the calculation of thermal as well
      as microcanonical rate constants.

PMID- 30109752
TI  - Longitudinal associations between food insecurity and substance use in a cohort
      of women with or at risk for HIV in the United States.
AB  - BACKGROUND AND AIMS: Few longitudinal studies have examined the relationship
      between food insecurity and substance use. We aimed to investigate this
      relationship using longitudinal data among women with or at risk for HIV in the
      United States. DESIGN: Women's Interagency HIV Study (WIHS), a prospective cohort
      study. SETTING: Nine sites across the United States. PARTICIPANTS: A total of
      2553 women with or at risk for HIV. MEASUREMENTS: Semi-annual structured
      interviews were conducted during April 2013-March 2016. Food security (FS) was
      the primary predictor, measured using the Household Food Security Survey Module.
      Outcomes were: any illicit substance use except cannabis; licit or illicit
      cannabis use; stimulant use (crack, cocaine, or methamphetamine); opioid use
      (heroin or methadone in a non-prescribed way); and prescription drug misuse
      (prescription narcotics, amphetamines, or tranquilizers in a non-prescribed way)
      since the last visit. We used multivariable logistic regression with random
      effects to examine longitudinal associations of current and previous FS with the
      outcomes simultaneously, adjusting for socio-demographic factors, HIV serostatus,
      physical health and health insurance. FINDINGS: Average number of visits was 4.6.
      At baseline, 71% of participants were HIV-seropositive, 44% reported marginal,
      low, or very low FS, and 13% were using illicit substances. In adjusted analyses,
      current low and very low FS were significantly associated with 1.59 [95%
      confidence interval (CI) = 1.02, 2.46; P = 0.039] and 2.48 (95% CI = 1.52, 4.04;
      P < 0.001) higher odds of any illicit substance use, compared to high FS, and
      also with higher odds of cannabis, stimulant and opioid use, exhibiting a
      consistent dose-response relationship. Marginal, low, and very low FS at the
      previous visit were associated with 1.66 (95% CI = 1.08, 2.54; P = 0.020), 1.77
      (95% CI = 1.14, 2.74; P = 0.011), and 2.28 (95% CI = 1.43, 3.64; P < 0.001)
      higher odds of current illicit substance use. CONCLUSIONS: Food insecurity
      appears to be longitudinally associated with substance use among US women with or
      at risk for HIV.

PMID- 30109754
TI  - Optical coherence tomography and molecular analysis of sudden acquired retinal
      degeneration syndrome (SARDS) eyes suggests the immune-mediated nature of retinal
      damage.
AB  - OBJECTIVE: To perform detailed analysis of retinal changes in dogs with SARDS
      using optical coherence tomography (OCT), funduscopy, and molecular analysis.
      ANIMALS: Subjects were 29 dogs from 12 US states and Canada diagnosed with SARDS
      by 8 ophthalmologists. An additional 7 eyes from 5 deceased SARDS dogs were used
      for molecular and histological analysis. PROCEDURES: Dogs were evaluated using
      chromatic pupil light reflex testing (cPLR), and electroretinography (ERG);
      subjects underwent complete ophthalmic examination, including funduscopy, retinal
      photography, and OCT, in addition to complete laboratory analysis, blood pressure
      evaluation, abdominal and thoracic radiographs, and computerized tomography (CT)
      imaging to assess possible systemic abnormalities. Histology and
      immunohistochemistry analysis was performed in 2 SARDS eyes. Microarray analysis
      was performed in 5 SARDS retinas. RESULTS: Thirty-eight percent of patients had
      <1-mm wide retinal detachments (RD) on OCT analysis, which could not be detected
      by funduscopy or retinal photographs. Systemic hypertension did not seem to be a
      contributing factor (RD 22.2%; ND 20%, Odds ratio = 1.1). No dogs showed
      neoplastic changes by thoracic or abdominal radiography, or CT imaging. There was
      no statistically significant difference in age (RD 7.9 +/- 1.9 years (mean +/-
      SD); ND 7.6 +/- 1.7 years, p = 0.69) or duration of blindness prior to
      presentation (RD 18 +/- 7 days (mean+/-SD); ND 21 +/- 12 days, p = 0.28).
      Microarray and histology analysis of SARDS eyes revealed molecular changes
      suggestive of immune-mediated damage. CONCLUSIONS: Observed histological,
      molecular, and OCT changes are highly suggestive of immune-mediated damage in
      SARDS eyes.

PMID- 30109755
TI  - Corneal collagen cross-linking following superficial keratectomy as treatment for
      corneal endothelial cell dystrophy in dogs: Preliminary clinical study.
AB  - OBJECTIVE: To describe the outcome of corneal collagen cross-linking (CXL)
      combined with superficial keratectomy (SK) as treatment for corneal edema due to
      corneal endothelial dystrophy (CED) in dogs. ANIMALS STUDIED: Four eyes of four
      dogs (3 Shih Tzus and 1 English Cocker Spaniel) with corneal edema due to CED
      were treated with SK and CXL. Two were males, and two were females. PROCEDURE:
      Depending on corneal thickness, 500-700 MUm of edematous cornea was removed by
      SK. Next, CXL was performed by irradiating the cornea with UVA (365 nm) at 3
      mW/cm2 irradiance for 30 min after soaking with 0.1% riboflavin in 20% dextran
      every three minutes for 30 minutes. One drop of riboflavin was instilled every
      three minutes during irradiation. Slit lamp biomicroscopy and optical coherence
      tomography were used to examine the cornea during the follow-up period. RESULTS:
      The corneas had focal to diffuse edema, and the average corneal thickness was
      1553 (1282-1900) MUm. All corneas showed a significantly reduced corneal
      thickness and regained marked transparency immediately after treatment; however,
      the opacity increased as the corneal thickness increased during the follow-up
      period. Corneal vascularization (n = 4) disappeared within a month. Corneal
      pigmentation (n = 1) and bullae (n = 1) were observed. All cases showed marked
      reduction in corneal thickness; however, transparency was improved in only one
      case. CONCLUSION: Collagen cross-linking with SK has the potential to reduce the
      corneal thickness in CED cases; however, a lasting clinically significant
      improvement of corneal transparency seems unlikely. As the added benefit of CXL
      to the SK procedure is unclear based on the results of this study, combined
      treatment of CXL and SK for the treatment of corneal edema caused by CED is
      currently not recommended in dogs.

PMID- 30109749
TI  - The nuclear receptor superfamily: A structural perspective.
AB  - Nuclear receptors (NRs) are a family of transcription factors that regulate
      numerous physiological processes such as metabolism, reproduction, inflammation,
      as well as the circadian rhythm. NRs sense changes in lipid metabolite levels to
      drive differential gene expression, producing distinct physiologic effects. This
      is an allosteric process whereby binding a cognate ligand and specific DNA
      sequences drives the recruitment of diverse transcriptional co-regulators at
      chromatin and ultimately transactivation or transrepression of target genes.
      Dysregulation of NR signaling leads to various malignances, metabolic disorders,
      and inflammatory disease. Given their important role in physiology and ability to
      respond to small lipophilic ligands, NRs have emerged as valuable therapeutic
      targets. Here, we summarize and discuss the recent progress on understanding the
      complex mechanism of action of NRs, primarily from a structural perspective.
      Finally, we suggest future studies to improve our understanding of NR signaling
      and better design drugs by integrating multiple structural and biophysical
      approaches.

PMID- 30109756
TI  - The use of sulfur hexafluoride microbubbles for contrast-enhanced ocular
      ultrasonography of the pecten oculi in birds.
AB  - BACKGROUND: The pecten oculi is a vascular and pigmented structure localized
      within the posterior segment of all avian eyes. Its primary function is not fully
      understood yet. OBJECTIVE: As ultrasonography (US) is a useful imaging modality
      for evaluation of the pecten oculi, the objective of this study was to
      investigate the utility of an intravenous contrast solution of sulfur
      hexafluoride (SF6) microbubbles as a means of enhancing visualization of the
      pecten oculi in normal birds. ANIMALS STUDIED: Ten adult individuals of the
      following avian species were evaluated: 1 roadside hawk (Rupornis magnirostris),
      1 stygian owl (Asio stygius), 2 striped owls (Asio clamator), 2 burrowing owls
      (Athene cunicularia), 2 ring-necked parakeet (Psittacula krameri), and 2 domestic
      chickens (Gallus gallus domesticus). PROCEDURE(S): After baseline ocular
      sonograms were obtained in sedated animals, 4.5 MUg/kg of a contrast solution
      containing SF6 microbubbles was administered intravenously and US of the right
      eye was immediately performed. US was continued during injection to provide real
      time imaging of the pecten oculi during vascular perfusion of contrast material.
      RESULTS: Within 2-3 seconds following intravenous contrast administration,
      microbubbles reached the pecten oculi of all birds investigated and provided
      significant ultrasonographic contrast enhancement. CONCLUSIONS: SF6 microbubble
      contrast ultrasonography in birds is a safe and easy procedure that provides
      increased contrast and enhanced visualization of the pecten oculi. Future use may
      enable further discovery of its physiologic functions and aid in the development
      of therapeutic plans for avian intraocular disease.

PMID- 30109757
TI  - Distinct biogeographic patterns of bacterioplankton composition and single-cell
      activity between the subtropics and Antarctica.
AB  - Bacterial biogeography and activity in the Southern Ocean are poorly understood
      to date. Here, we applied CARD-FISH to quantify bacterial community structure
      from the subtropics to Antarctica between 10 degrees W and 10 degrees E, covering
      four biogeographic provinces with distinct environmental properties. In addition,
      incorporation of radiolabeled glucose, amino acids and leucine via MAR-FISH
      served to quantify the contribution to substrate turnover by selected bacterial
      groups. SAR11, Bacteroidetes, Gammaproteobacteria and the Roseobacter group
      accounted for the majority of the bacterial community (52%-88% of DAPI-stained
      cells) but showed little distributional variation between provinces. In contrast,
      taxonomic subclades Polaribacter, NS5, NS2b (Bacteroidetes) as well as RCA
      (Roseobacter group) featured marked geographic variation, illustrated by NMDS and
      coefficients of variation. Roseobacter (specifically RCA) and Gammaproteobacteria
      constituted considerable fractions of cells incorporating glucose and amino acids
      respectively. Bacteroidetes had generally lower activities, but Polaribacter
      accounted for a major fraction of biomass production at one station near the
      Antarctic ice shelf. In conclusion, distributional patterns at finer taxonomic
      level and highest substrate turnover by less abundant taxa highlight the
      importance of taxonomic subclades in marine carbon fluxes, contributing to the
      understanding of functional bacterial biogeography in the Southern Ocean.

PMID- 30109758
TI  - Aspartate metabolism is involved in the maintenance of enterohaemorrhagic
      Escherichia coli O157:H7 in bovine intestinal content.
AB  - The gastrointestinal tract (GIT) of healthy cattle is the main reservoir of
      enterohaemorrhagic Escherichia coli (EHEC). Therefore, it is crucial to better
      understand the physiology of EHEC in the bovine GIT. In this study, we
      demonstrate that aspartate present in bovine small intestine content (BSIC), was
      exhausted after incubation of the reference EHEC strain EDL933 but was poorly
      assimilated by the endogenous microbiota. Furthermore, the bovine commensal E.
      coli strain BG1 appeared less efficient than EDL933 in aspartate assimilation
      suggesting a competitive ability of EHEC to assimilate this amino acid. Our
      results strongly suggest that aspartate, internalized via the DcuA aspartate:
      succinate antiporting system, is then converted to fumarate and carbamoyl
      aspartate, the precursor for UMP biosynthesis. Aspartate assimilation by these
      two pathways conferred a competitive growth advantage to EHEC in BSIC. In
      summary, supply of intracellular fumarate due to aspartate deamination and used
      as an electron acceptor for anaerobic fumarate respiration, as well as de novo
      synthesis of pyrimidine from aspartate appear to be important pathways favouring
      EHEC persistence in the bovine gut. Aspartate probably represents an ecological
      niche for EHEC in the bovine small intestine.

PMID- 30109759
TI  - Rapamycin for refractory discoid lupus erythematosus.
AB  - Generalized discoid lupus erythematosus can pose a therapeutic challenge for
      dermatologists. Current treatment emphasizes photoprotection, topical and
      systemic steroids, and steroid-sparing immunosuppressive agents if necessary.
      Rapamycin, also known as sirolimus, selectively inhibits mammalian target of
      rapamycin, a regulatory kinase responsible for multiple signal transduction
      pathways. Mammalian target of rapamycin inhibition reduces cell division,
      lymphocyte proliferation, cytokine release, and downstream pathways unique from
      other classes of immunomodulatory drugs. Herein, we present a case of generalized
      discoid lupus erythematosus resistant to topical steroids, prednisone,
      azathioprine, mycophenolate mofetil, hydroxychloroquine, and thalidomide. The
      addition of rapamycin led to a positive treatment response within 6 weeks, with
      good tolerance of the medication and no adverse effects. The current literature
      supporting the use of rapamycin in the treatment of autoimmune connective tissue
      diseases is also briefly reviewed. For patients with severe or generalized
      discoid lupus erythematosus refractory to conventional treatment, rapamycin may
      be a useful therapeutic consideration.

PMID- 30109760
TI  - From MARS to MAGIC: The remarkable journey through time and space of the Grading
      of Recommendations Assessment, Development and Evaluation initiative.
AB  - For over 30 years, "evidence-based" clinical guidelines remained entrenched in an
      oversimplified, design-based, framework for rating the strength of evidence
      supporting clinical recommendations. The approach frequently equated the rating
      of evidence with that of the recommendations themselves. "Grading Recommendations
      Assessment, Development and Evaluation (GRADE)" has emerged as a proposed
      antidote to obsolete guideline methodology. GRADE sponsors and collaborators are
      in the process of attempting to amplify and extend the framework to encompass
      implementation and adaptation of guidelines, above and beyond the evaluation and
      rating of clinical research. Alternative schemes and models for such extensions
      are beginning to appear. This commentary reviews the strengths and weaknesses of
      GRADE with reference to other recent critiques. It considers the GRADE Working
      Group's "evidence-to-decision" extension of the evidence rating framework,
      together with proposed alternatives. It identifies pitfalls of the GRADE system's
      cooptation of relational processes necessary to the interpretation and uptake of
      recommendations that properly belong to end-users. It also identifies dangers
      inherent in blurring important boundaries between clinical and policy
      applications of guidelines. Finally, it addresses criticisms regarding the lack
      of a theoretical framework supporting the different facets of the GRADE approach
      and proposes a social constructivist orientation to clinical guideline
      development and use. Recommendations are offered to potential guideline
      developers and users regarding how to draw upon the strengths of the GRADE
      framework without succumbing to its pitfalls.

PMID- 30109761
TI  - Rationally Designed Fluorescence . OH Probe with High Sensitivity and Selectivity
      for Monitoring the Generation of . OH in Iron Autoxidation without Addition of H2
      O2.
AB  - The first sensitive fluorescence . OH probe (1) that is capable of monitoring the
      generation of trace . OH in iron autoxidation is presented. The probe 1 was
      designed by utilizing both the unique aromatic hydroxylation and the
      electrophilicity of . OH, and prepared by incorporating a strong electron
      donating methoxy group into a cyanine fluorochrome to enhance the trapping
      ability for . OH. Reaction of 1 with . OH leads to a larger pi-conjugation
      formation and near-infrared fluorescence off-on response. The capability of probe
      1 has been demonstrated by imaging . OH generated in living cells under iron
      autoxidation as well as various stimuli, which reveals that the basal level of .
      OH in RAW 264.7 cells is lower than that in HeLa cells. The superior analytical
      performance of probe 1 makes it useful for detecting trace . OH in some critical
      physiological and pathological processes associated with iron autoxidation.

PMID- 30109762
TI  - Health-e mums: Evaluating a smartphone app design for diabetes prevention in
      women with previous gestational diabetes.
AB  - AIM: Women with prior gestational diabetes have increased risk for developing
      type 2 diabetes postpartum. While diabetes prevention programs are effective in
      reducing a woman's risk, the reach of traditional face-to-face programs is poor
      in this population and using a mHealth approach appears to be promising. We aimed
      to evaluate a pilot smartphone app developed from an evidence-based diabetes
      prevention program specifically for women with previous gestational diabetes
      mellitus using a series of focus groups to explore the app functionality and
      messaging. METHODS: The Health-e Mums app underwent an iterative, three-phase
      development: initial development, wireframe development and pilot testing. Twenty
      six women participated in four focus groups during the pilot-testing phase. The
      focus group transcripts were analysed thematically to evaluate the app
      functionality and user-experience. RESULTS: Focus group participants identified
      diabetes screening confusion and a need for personalisation as sub-themes within
      the app functionality theme. The user-experience exploration found generally
      positive findings but participants had mixed responses to the utility of video
      segments and applying milestones relating to diabetes prevention guidelines.
      CONCLUSIONS: A user-centred approach was taken to develop a diabetes prevention
      program app for women with prior gestational diabetes. Women were predominantly
      satisfied with the overall app design, how it functioned and what the user
      experience would be like when fully developed.

PMID- 30109763
TI  - MicroPulseTM transscleral cyclophotocoagulation in the treatment of canine
      glaucoma: Preliminary results (12 dogs).
AB  - OBJECTIVE: To describe the clinical application and effect of MicroPulseTM
      transscleral cyclophotocoagulation (MP-TSCPC) in dogs with glaucoma. ANIMALS
      STUDIED: Twelve dogs with primary (n = 8) or secondary (n = 4) glaucoma, aged 2
      13 years (mean +/- SD, 7.2 +/- 3.8 years). PROCEDURES: MP-TSCPC was performed
      under sedation or general anesthesia. Laser duty cycle was 31.3%, laser power
      varied from 2000-2800 mW, and each hemisphere was treated for 90-180 seconds. The
      probe was applied to each quadrant in a "sweeping motion," sparing the 3 and 9
      o'clock positions. RESULTS: The number of MP-TSCPC procedures per eye varied from
      1 to 3 (1.4 +/- 0.7). Intraocular pressure (IOP) was controlled (<25 mm Hg) in
      11/12 dogs (92%) within 1-15 days post-operatively. The IOP control at 1 month
      and the duration between repeated procedures were significantly greater in eyes
      treated with high energy laser (2800 mW) compared to 2000-2500 mW. Long-term
      follow-up (315.3 +/- 100.7 days) showed controlled IOP in 5/12 (42%) and vision
      retention in 4/8 (50%) dogs. In unsuccessful cases, loss of IOP control or vision
      loss occurred within 3-245 days (109.1 +/- 93.7 days) and 28-261 days (114 +/-
      101.6 days), respectively, resulting in a salvage procedure in 6 dogs.
      Complications were as follows: corneal hypoesthesia (92%), anterior uveitis
      (67%), post-operative ocular hypertension (50%), neurotrophic corneal ulcer
      (25%), keratoconjunctivitis sicca (8%), and rubeosis iridis (8%). CONCLUSIONS: MP
      TSCPC is a viable tool for managing canine glaucoma, although further studies are
      required to improve the long-term effect and reduce the complication rate.

PMID- 30109765
TI  - Ionic Modulation of the Interfacial Magnetism in a Bilayer System Comprising a
      Heavy Metal and a Magnetic Insulator for Voltage-Tunable Spintronic Devices.
AB  - The voltage modulation of yttrium iron garnet (YIG) is of practical and
      theoretical significance; due to its advantages of compactness, high-speed
      response, and energy efficiency, it can be used for various spintronic
      applications, including spin-Hall, spin-pumping, and spin-Seebeck effects. In
      this study, a significant ferromagnetic resonance change is achieved within the
      YIG/Pt bilayer heterostructures uisng ionic modulation, which is accomplished by
      modifying the interfacial magnetism in the deposited "capping" platinum layer.
      With a small voltage bias of 4.5 V, a large ferromagnetic field shift of 690 Oe
      is achieved in heterostructures of YIG (13 nm)/Pt (3 nm)/(ionic liquid, IL)/(Au
      capacitor). The remarkable magnetoelectric (ME) tunability comes from the
      additional and voltage-induced ferromagnetic ordering, caused by uncompensated d
      orbital electrons in the Pt metal layer. Confirmed by first-principle
      calculations, this finding paves the way for novel voltage-tunable YIG-based
      spintronics.

PMID- 30109764
TI  - Are component endpoints equal? A preference study into the practice of composite
      endpoints in clinical trials.
AB  - OBJECTIVES: To examine patients' perspectives regarding composite endpoints and
      the utility patients put on possible adverse outcomes of revascularization
      procedures. DESIGN: In the PRECORE study, a stated preference elicitation method
      Best-Worst Scaling (BWS) was used to determine patient preference for 8 component
      endpoints (CEs): need for redo percutaneous coronary intervention (PCI) within 1
      year, minor stroke with symptoms <24 hours, minor myocardial infarction (MI) with
      symptoms <3 months, recurrent angina pectoris, need for redo coronary artery
      bypass grafting (CABG) within 1 year, major MI causing permanent disability,
      major stroke causing permanent disability and death within 24 hours. SETTING: A
      tertiary PCI/CABG centre. PARTICIPANTS: One hundred and sixty patients with
      coronary artery disease who underwent PCI or CABG. MAIN OUTCOME MEASURES:
      Importance weights (IWs). RESULTS: Patients considered need for redo PCI within 1
      year (IW: 0.008), minor stroke with symptoms <24 hours (IW: 0.017), minor MI with
      symptoms <3 months (IW: 0.027), need for redo CABG within 1 year (IW: 0.119),
      recurrent angina pectoris (IW: 0.300) and major MI causing permanent disability
      (IW: 0.726) less severe than death within 24 hours (IW: 1.000). Major stroke
      causing permanent disability was considered worse than death within 24 hours (IW:
      1.209). Ranking of CEs and the relative values attributed to the CEs differed
      among subgroups based on gender, age and educational level. CONCLUSION: Patients
      attribute different weight to individual CEs. This has significant implications
      for the interpretation of clinical trial data.

PMID- 30109766
TI  - No pancreatic safety concern following glucagon-like peptide-1 receptor agonist
      therapies: A pooled analysis of cardiovascular outcome trials.
AB  - AIMS: Evidence on the pancreatic safety of glucagon-like peptide-1 receptor
      agonist therapy has been limited. The objective of the study was to investigate
      this issue by pooling data on the incidence of acute pancreatitis and pancreatic
      cancer from four large-scale cardiovascular outcome trials of glucagon-like
      peptide-1 receptor agonists. MATERIALS AND METHODS: Data were extracted from four
      published cardiovascular outcome trials of glucagon-like peptide-1 receptor
      agonists in patients with type 2 diabetes, and pooled analysis was performed to
      evaluate the risk of acute pancreatitis and pancreatic cancer associated with
      glucagon-like peptide-1 receptor agonist treatment. Peto OR with 95% CI was used
      for risk evaluation. RESULTS: The four cardiovascular outcome trials enrolled a
      total of 33 457 patients with type 2 diabetes and reported 123 patients with
      acute pancreatitis and 70 patients with pancreatic cancer during the median
      follow-ups of 2.1 to 3.8 years. There was no increased risk of either acute
      pancreatitis (Peto OR 0.89 [95% CI 0.63, 1.27]) or pancreatic cancer (Peto OR
      0.84 [95% CI 0.53, 1.35]) associated with glucagon-like peptide-1 receptor
      agonists compared with placebo when added to standard care. CONCLUSIONS: Combined
      analysis of the four cardiovascular outcome trials showed that treatment with
      glucagon-like peptide-1 receptor agonists was not associated with an increased
      risk of either acute pancreatitis or pancreatic cancer in patients with type 2
      diabetes. Our new analysis further supports the previously reported results.

PMID- 30109768
TI  - Bacteria inhabiting deadwood of 13 tree species are heterogeneously distributed
      between sapwood and heartwood.
AB  - Deadwood represents an important structural component of forest ecosystems, where
      it provides diverse niches for saproxylic biota. Although wood-inhabiting
      prokaryotes are involved in its degradation, knowledge about their diversity and
      the drivers of community structure is scarce. To explore the effect of deadwood
      substrate on microbial distribution, the present study focuses on the microbial
      communities of deadwood logs from 13 different tree species investigated using an
      amplicon based deep-sequencing analysis. Sapwood and heartwood communities were
      analysed separately and linked to various relevant wood physico-chemical
      parameters. Overall, Proteobacteria, Acidobacteria and Actinobacteria represented
      the most dominant phyla. Microbial OTU richness and community structure differed
      significantly between tree species and between sapwood and heartwood. These
      differences were more pronounced for heartwood than for sapwood. The pH value and
      water content were the most important drivers in both wood compartments. Overall,
      investigating numerous tree species and two compartments provided a remarkably
      comprehensive view of microbial diversity in deadwood.

PMID- 30109769
TI  - Stereoselective Solid-State Synthesis of Substituted Cyclobutanes Assisted by
      Pseudorotaxane-like MOFs.
AB  - Regioselective photodimerization of trans-4-styrylpyridine (4-spy) derivatives is
      performed using pseudorotaxane-like Zn-based metal organic frameworks MOFs as
      templates. The formation of rctt-HT (head-to-tail) dimers is achieved by
      confining pairs of coordinated 4-spy derivative ligands within hexagonal windows
      and then irradiating them with UV light. It is also possible to achieve a
      photodimerization reaction where two different substituted 4-spy ligands are
      included in such a MOF material. The ether bond formation is employed to protect
      the sensitive -OH group of HO-spy and the methyl group of CH3 O-spy is
      subsequently removed after the formation of cyclobutane derivative in the CH3 O
      spy-based MOF. Introducing substituents at the 2- or 3-position of the phenyl
      group of 4-spy does not significantly affect the rate of the dimerization process
      except in the case of the strongly electron-withdrawing nitro group where the
      rate is significantly decreased. These results are in striking contrast to the
      mixtures of photoproducts and low yields obtained by untemplated
      photodimerization in organic solvents.

PMID- 30109770
TI  - High Performance Flexible Organic Electrochemical Transistors for Monitoring
      Cardiac Action Potential.
AB  - Flexible and transparent electronic devices possess crucial advantages over
      conventional silicon based systems for bioelectronic applications since they are
      able to adapt to nonplanar surfaces, cause less chronic immunoreactivity, and
      facilitate easy optical inspection. Here, organic electrochemical transistors
      (OECTs) are embedded in a flexible matrix of polyimide to record cardiac action
      potentials. The wafer-scale fabricated devices exhibit transconductances (12 mS V
      1 ) and drain-source on-to-off current ratios (~105 ) comparable to state of the
      art nonflexible and superior to other reported flexible OECTs. The transfer
      characteristics of the devices are preserved even after experiencing extremely
      high bending strain and harsh crumpling. A sub-micrometer poly(3,4
      ethylenedioxythiophene) doped with poly(styrenesulfonate) layer results in a fast
      transport of ions between the electrolyte and the polymer channel characterized
      by a cut-off frequency of 1200 Hz. Excellent device performance is proved by
      mapping the propagation of cardiac action potentials with high signal-to-noise
      ratio. These results demonstrate that the electrical performance of flexible
      OECTs can compete with hard-material-based OECTs and thus potentially be used for
      in vivo applications.

PMID- 30109767
TI  - Altered modulation of lamin A/C-HDAC2 interaction and p21 expression during
      oxidative stress response in HGPS.
AB  - Defects in stress response are main determinants of cellular senescence and
      organism aging. In fibroblasts from patients affected by Hutchinson-Gilford
      progeria, a severe LMNA-linked syndrome associated with bone resorption,
      cardiovascular disorders, and premature aging, we found altered modulation of
      CDKN1A, encoding p21, upon oxidative stress induction, and accumulation of
      senescence markers during stress recovery. In this context, we unraveled a
      dynamic interaction of lamin A/C with HDAC2, an histone deacetylase that
      regulates CDKN1A expression. In control skin fibroblasts, lamin A/C is part of a
      protein complex including HDAC2 and its histone substrates; protein interaction
      is reduced at the onset of DNA damage response and recovered after completion of
      DNA repair. This interplay parallels modulation of p21 expression and global
      histone acetylation, and it is disrupted by LMNAmutations leading to progeroid
      phenotypes. In fact, HGPS cells show impaired lamin A/C-HDAC2 interplay and
      accumulation of p21 upon stress recovery. Collectively, these results link
      altered physical interaction between lamin A/C and HDAC2 to cellular and organism
      aging. The lamin A/C-HDAC2 complex may be a novel therapeutic target to slow down
      progression of progeria symptoms.

PMID- 30109771
TI  - Constituents of "teabacco": A forensic analysis of cigarettes made from diverted
      nicotine replacement therapy lozenges in smoke-free prisons.
AB  - Following the implementation of prison smoke-free policies, there have been
      reports of prisoners creating substitute cigarettes made from nicotine
      replacement therapy patches or lozenges infused with tea leaves ("teabacco"). No
      studies have analyzed the chemical constituents of teabacco made from nicotine
      lozenges, so as to document any potential related health hazards. Teabacco
      samples were made by a participant who reported creating teabacco while
      incarcerated in a smoke-free prison in Queensland, Australia, and the process was
      video-recorded for replication in a laboratory. A simple linear smoking system
      captured the teabacco smoke for analysis. Inductively coupled plasma optical
      emission spectroscopy (ICP-OES) was used to analyze elemental composition and gas
      chromatography coupled with a mass spectrometer (GC-MS) analyzed the captured
      smoke using the National Institute of Standards and Technology mass spectral
      library. Analyses determined that quantities of copper, aluminum, and lead
      concentrations, and levels of inhaled total particulate matter, were above
      recommended guidelines for safe ingestion. Analysis of teabacco smoke using GC-MS
      identified potentially toxic compounds catechol and nicotine. However, our
      findings show that smoking this form of teabacco is less harmful than smoking
      teabacco made from nicotine patches, or smoking traditional tobacco cigarettes.
      Considering the limited potential health harm of smoking teabacco made from
      lozenges, and that nicotine lozenges represent the only form of smoking cessation
      support for individuals entering smoke-free prisons, we caution against the
      removal of nicotine lozenges from Queensland's prisons, at least until further
      research directly establishes health harms associated with this form of teabacco.

PMID- 30109772
TI  - Semiconducting Polymer Nanobiocatalysts for Photoactivation of Intracellular
      Redox Reactions.
AB  - An organic semiconducting polymer nanobiocatalyst (SPNB) composed of a
      semiconducting polymer core conjugated with microsomal cytochrome P450 (CYP) has
      been developed for photoactivation of intracellular redox. The core serves as the
      light-harvesting unit to initiate photoinduced electron transfer (PET) and
      facilitate the regeneration of dihydronicotinamide adenine dinucleotide phosphate
      (NADPH), while CYP is the catalytic center for intracellular redox. Under light
      irradiation, the semiconducting core can efficiently catalyze the generation of
      NADPH with a turnover frequency (TOF) 75 times higher than the reported
      nanosystems, ensuring the supply of the cofactor for intracellular redox. SPNB
      mediated intracellular redox thus can be efficiently activated by light in living
      cells to convert the model substrate and also to trigger the bioactivation of
      anticancer drugs. This study provides an organic nanobiocatalytic system that
      allows light to remotely control intracellular redox in living systems.

PMID- 30109773
TI  - Crystalline Ru0.33 Se Nanoparticles-Decorated TiO2 Nanotube Arrays for Enhanced
      Hydrogen Evolution Reaction.
AB  - Nowadays, the state-of-the-art electrocatalysts for hydrogen evolution reaction
      (HER) are platinum group metals. Nonetheless, Pt-based catalysts show decreased
      HER activity in alkaline media compared with that in acidic media due to the
      sluggish dissociation process of H2 O on the surface of Pt. With a cost 1/25 that
      of Pt, Ru demonstrates a favorable dissociation kinetics of absorbed H2 O.
      Herein, crystalline Ru0.33 Se nanoparticles are decorated onto TiO2 nanotube
      arrays (TNAs) to fabricate Ru0.33 Se @ TNA hybrid for HER. Owing to the large
      specific surface area, Ru0.33 Se nanoparticles are freely distributed and the
      particle aggregation is eliminated, providing more active sites. The contracted
      electron transport pathway rendered by TiO2 nanotubes and the synergistic effect
      at the interface significantly improve the charge transfer efficiency in the
      hybrid catalyst. Compared with Ru0.33 Se nanoparticles deposited directly on the
      Ti foil (Ru0.33 Se/Ti) or carbon cloth (Ru0.33 Se/CC), Ru0.33 Se @ TNA shows an
      enhanced catalytic activity with an overpotential of 57 mV to afford a current
      density of 10 mA cm-2 , a Tafel slope of 50.0 mV dec-1 . Furthermore, the hybrid
      catalyst also exhibits an outstanding catalytic stability. The strategy here
      opens up a new synthetic avenue to the design of highly efficient hybrid
      electrocatalysts for hydrogen production.

PMID- 30109774
TI  - The Authors reply: "Dual energy X-ray absorptiometry: gold standard for muscle
      mass?" by Scafoglieri et al.

PMID- 30109775
TI  - Detection of the designer benzodiazepine flunitrazolam in urine and preliminary
      data on its metabolism.
AB  - Designer benzodiazepines have emerged as recreational drugs. They are available
      via the Internet without control and are found in the form of falsified (fake)
      medicines. For some of them, limited information concerning their effects, their
      toxicity, and their detection in bio fluids is available in the literature. For
      others, nothing has been published, as in the case of flunitrazolam (FNTZ). To
      gain preliminary data on its elimination parameters in urine and to investigate
      its metabolism, one of the authors ingested one pink tablet bought on the
      Internet, after confirming the absence of other compounds and agreement with the
      labeled dosage (0.25 mg) by nuclear magnetic resonance (NMR). A software
      algorithm (MetaboLynx, Waters, Milford, MA, USA) was used to predict FNTZ
      biotransformation and four potential metabolites were proposed: 4-hydroxy-FNTZ,
      desnitro-FNTZ, 7-amino-FNTZ, and 7-acetamido-FNTZ. Urine samples were collected
      over 72 hours following oral administration of one tablet. After liquid/liquid
      extraction at pH 9.5, FNTZ concentrations were determined using ultra performance
      liquid chromatography-triple quadrupole-mass spectrometry (UPLC-QqQ-MS/MS). FNTZ
      remained detectable in hydrolyzed urine for 21 hours after ingestion, with
      concentrations ranging between 1 and 18 ng/mL. About 3% of the initial dose was
      excreted in urine as total unchanged FNTZ during this period. In vitro
      experiments (HLM incubations) were performed using ultra performance liquid
      chromatography-quadrupole time of flight-mass spectrometry (UPLC-QTOF-MS) in
      order to investigate the potential CYP- and UGT-dependent metabolites where only
      7-amino-FNTZ was detected as the only metabolite. However, in the urine
      specimens, desnitro-FNTZ, 7-acetamido-FNTZ and 7-amino-FNTZ were the main
      detected compounds. The identification of FNTZ metabolites dramatically improves
      the detection windows of the drug up to 37 hours.

PMID- 30109776
TI  - Folic Acid Derived Bimetallic-Doped Hollow Carbon Nanostructures for Efficient
      Electrocatalytic Oxygen Evolution.
AB  - Hydrogen production is one of the most effective methods for combating the global
      energy crisis. However, improving the electrochemical performance of oxygen
      evolution catalysts is a significant challenge. In this paper, exceptionally
      active electrocatalysts for oxygen-evolution reactions (OERs) were successfully
      developed and characterized by using SEM, TEM, XRD, BET, and X-ray photoelectron
      spectroscopy. The nitrogen-doped hollow-carbon-encapsulated bimetallic
      nanoparticles (MM'-NHCNPs) were prepared by using folic acid coordination
      polymerization. The hollow structure and the synergistic effect of bimetallic
      doping exhibited remarkable catalytic performance and outstanding stability for
      the OER in a 1.0 m KOH alkaline electrolyte. For the OER, the overpotential of
      the best catalyst was only 350 mV at a current density of 10 mA cm-2 with a small
      Tafel slope of 58 mV dec-1 . High durability was also demonstrated by the MM'
      NHCNPs. Such an MM'-NHCNP catalyst with excellent electrochemical properties
      provides a promising material for OERs.

PMID- 30109777
TI  - Efficacy of icotinib in advanced lung squamous cell carcinoma.
AB  - BACKGROUND: There are controversial data supporting the efficacy of epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in patients with
      advanced lung squamous cell carcinoma (SCC). In this study, the efficacy of
      icotinib in unselected and EGFR-mutated patients with lung SCC was assessed.
      METHODS: We retrospectively analyzed the survival time of unselected advanced
      lung SCC patients treated with icotinib for at least 5 months between June 2013
      and June 2016, and selected appropriate EGFR-mutated advanced lung ADC patients
      to have 1:1 ratio of propensity score matching with EGFR-mutated advanced lung
      SCC patients, and matching factors were age, sex, clinical stage, Karnofsky
      performance status (KPS), smoking history, EGFR mutation type, and treatment
      lines. RESULTS: A total of 487 unselected advanced lung SCC patients were
      available for analysis of icotinib treatment efficacy. The progression-free
      survival (PFS) was 13.0 months (95% CI 12.2-13.8), the overall survival (OS) was
      16.0 months (95% CI 14.7-17.3), and the objective response rate (ORR) was 41.3%.
      After propensity score matching, 78 EGFR-mutated lung SCC and 78 EGFR-mutated
      lung ADC patients were selected and compared. Although no statistical difference
      was found, ADC patients were associated with a longer PFS (15.8 months vs 12.7
      months, P = 0.275) and OS (24.2 months vs 18.5 months, P = 0.150), and a better
      ORR (59.0% vs 48.7%, P = 0.199) than compared with SCC patients when treated with
      icotinib. CONCLUSION: Icotinib has a modest therapeutic effect in patients with
      advanced lung SCC, especially for the population with EGFR mutations.

PMID- 30109778
TI  - Aging-related anorexia and its association with disability and frailty.
AB  - BACKGROUND: Anorexia of ageing may be a precursor to various geriatric syndromes.
      We elucidated whether anorexia of ageing had a significant impact on incident
      disability and investigated whether anorexia of ageing had a direct association
      with future disability or an indirect association with disability via frailty.
      METHODS: This study employed an observational, longitudinal, cohort design in a
      community setting. Participants were 4393 older adults (75.9 +/- 4.3 years).
      Anorexia of ageing was assessed by a simplified nutritional appetite
      questionnaire. Frailty was operationalized as slowness, weakness, exhaustion, low
      physical activity, and weight loss. Participants who had none of these
      characteristics were considered robust, those with one or two characteristics
      were considered pre-frail, and those with three or more characteristics were
      considered frail. We examined sociodemographic variables (age, sex, and
      education), medical history (medication and chronic disease history), lifestyle
      factors (smoking and drinking habits and living arrangement), body mass index,
      blood nutrition data, depressive symptoms, physical functioning, and cognitive
      functioning. RESULTS: The prevalence of anorexia of ageing was 10.7% (n = 468).
      The proportion of physical frailty, pre-frailty, and robustness were 8.4, 52.0,
      and 39.6%, respectively, in the without anorexia of ageing group, and 20.3, 57.7,
      and 22.0%, respectively, in the anorexia of ageing group (P < 0.001). During a 2
      year follow-up, the prevalence proportion of disability was 5.6% in the without
      anorexia of ageing group and 10.7% in the anorexia of ageing group (P < 0.001).
      Adjusted for covariates (except for frailty status), the participants with
      anorexia of ageing had an independently associated higher risk of incident
      disability compared with those without anorexia of ageing (hazard ratio: 1.43,
      95% confidence interval: 1.04-1.95, P = 0.03). However, adjusted for covariates
      (including frailty status), anorexia of ageing was not significantly associated
      with incident disability (P = 0.09). Structural equation models revealed that
      anorexia of ageing had no direct effect on disability; however, anorexia of
      ageing was associated with frailty. CONCLUSIONS: Older adults with anorexia of
      ageing had a higher proportion of frailty and a higher prevalence proportion of
      disability compared with those without anorexia of ageing. Although anorexia of
      ageing may not have a direct effect on incident disability, the structural
      equation model suggests an indirect relationship between anorexia of ageing and
      incident disability via frailty status.

PMID- 30109779
TI  - Room-Temperature Synthesis of Covalent Organic Framework (COF-LZU1) Nanobars in
      CO2 /Water Solvent.
AB  - The development of facile, rapid, low-energy, environmentally benign routes for
      the synthesis of covalent organic frameworks (COFs) is of great interest. This
      study concerns the utilization of water containing dissolved CO2 as a solvent for
      the room-temperature synthesis of COF. The as-synthesized particles, denoted COF
      LZU1, combine advantages of good crystallinity, nanoscale size, and high surface
      area, which suggests promising application as a support for heterogeneous
      catalysts. Moreover, this versatile CO2 -assisted method is also applicable for
      the room-temperature synthesis of Cu-COF-LZU1. This method gives rise to new
      opportunities for fabricating COFs and COF-based materials with different
      compositions and structures.

PMID- 30109780
TI  - Apatinib targets both tumor and endothelial cells in hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed malignancies
      worldwide with poor prognosis and tends to be hypervascular. Aberrant expression
      of the vascular endothelial growth factor 2 (VEGFR-2) has been implicated in the
      progression of HCC and represents a valid target for anticancer therapy.
      Apatinib, a small molecule inhibitor of VEGFR-2 tyrosine kinase, shows strong
      antitumor activity in various tumors. This study is designed to evaluate the
      activity of apatinib on both human umbilical vein vascular endothelial cells
      (HUVECs) and HCC cell lines (in vitro and in vivo), and also to investigate the
      characteristics and possible mechanisms underlying these effects by molecular
      biology methods. Following the results in our study, apatinib inhibited
      phosphorylation of VEGFR-2 in HUVECs and blocked in vitro endothelial cell
      migration and tube formation. Concentration-dependent antiproliferative effects
      of apatinib were also observed in all 6 HCC cell lines including SK-Hep-1, HepG2,
      Hep3B, Huh-7, PLC/PRF/5, SMMC-7721. Moreover, response to apatinib of HCC cell
      lines was significantly correlated with VEGFR-2 expression level. Additionally,
      apatinib significantly inhibit VEGF-triggered VEGFR-2 phosphorylation and
      activation of downstream signaling molecules such as Akt and ERK1/2 in HCCs.
      Apatinib can also induce a cell cycle arrest at G2/M phase and promote HCC
      apoptosis tested in vitro. In vivo data showed that apatinib can effectively
      inhibit tumor growth, decreased angiogenesis, as well as induced HCC apoptosis
      (in some tumors), and thus prolonged animal survival in a mouse xenograft model
      of human HCC. Our findings suggested that apatinib is a highly potent, oral
      active anti-angiogenic, and anti-HCC agent. The results from current study
      provide a clear biological rationale to evaluate apatinib as a new agent in HCC
      in clinical setting, especially for the VEGFR-2 overexpression ones.

PMID- 30109781
TI  - Impact of coexistent chronic obstructive pulmonary disease on the survival of
      patients with small cell lung cancer receiving chemotherapy.
AB  - BACKGROUND: While there is growing interest in the correlation between chronic
      obstructive pulmonary disease (COPD) and non-small cell lung cancer, very few
      studies have examined the interaction between COPD and small cell lung cancer
      (SCLC). Therefore, the aim of this study was to examine the impact of COPD on the
      survival of patients with SCLC. METHODS: The medical records of 110 patients with
      SCLC who received chemotherapy from July 2006 until April 2014 were
      retrospectively examined. The overall survival (OS) and progression-free survival
      (PFS) rates of spirometry-diagnosed COPD and non-COPD groups were compared.
      Predictors for poorer survival were analyzed using Cox proportional hazards
      regression. RESULTS: Of the 110 SCLC patients, 57 (51.8%) had coexistent COPD.
      The median OS for the COPD group was 11.6 months and for the non-COPD group was
      11.2 months (log-rank test, P = 0.581), whereas the median PFS rates were 6.65
      and 6.57 months, respectively (log-rank test, P = 0.559). Multivariate analysis
      identified Eastern Cooperative Oncology Group performance status >= 2 and
      extensive-stage SCLC as independent risk factors for shorter OS; however,
      coexisting COPD was not a predictor of survival. CONCLUSIONS: Although over half
      of the SCLC patients receiving chemotherapy had COPD, coexisting COPD had no
      impact on the survival of patients with SCLC.

PMID- 30109782
TI  - The regulatory role of APE1 in epithelial-to-mesenchymal transition and in
      determining EGFR-TKI responsiveness in non-small-cell lung cancer.
AB  - BACKGROUND: Epithelial-to-mesenchymal transition (EMT) plays a pivotal role in
      resistance to EGFR tyrosine kinase inhibitors (TKIs) in non-small-cell lung
      cancer (NSCLC). Our previous study revealed that in osteosarcoma, human
      apurinic/apyrimidinic endonuclease 1 (APE1) regulates transforming growth factor
      beta (TGF-beta), an important player in EMT. We therefore hypothesized a link
      between APE1 and EGFR-TKI responsiveness in NSCLC. METHODS: The protein levels of
      APE1 were analyzed in tumors of NSCLC patients receiving EGFR-TKI treatment. The
      correlation between APE1 expression and progression-free survival (PFS), overall
      survival (OS), or response rate were analyzed. The impact of APE1 on the response
      to EGFR-TKIs was measured by exogenous manipulation of APE1 in EGFR-TKI-sensitive
      and EGFR-TKI-resistant cells. RESULTS: We indicate that low expression of APE1 in
      tumors is associated with a significantly longer PFS (20.8 months vs 8.4 months,
      P = 0.008) and a preferential OS (39.0 months vs 17.0 months, P = 0.001), with no
      difference in initial response rate to EGFR-TKIs. We observed that APE1 protein
      level was significantly increased in EGFR-TKI-resistant cells and was associated
      with downregulated E-cadherin and upregulated vimentin. The EMT phenotype, as
      well as the levels of TGF-beta, was suppressed in APE1 knockdown HCC827/IR and PC
      9/ER cells, while the EMT phenotype was promoted in APE1-overexpressed HCC827 and
      PC-9 cells. Furthermore, a specific APE1 redox inhibitor (ie, E3330) effectively
      reversed the EMT phenotype and further sensitized the cells to EGFR-TKIs.
      CONCLUSION: This study revealed a significant role of APE1 in EGFR-TKI resistance
      via novel regulatory effects on the EMT phenotype in NSCLC.

PMID- 30109784
TI  - Calcium-Polystyrene Sulfonate Decreases Inter-Dialytic Hyperkalemia in Patients
      Undergoing Maintenance Hemodialysis: A Prospective, Randomized, Crossover Study.
AB  - Hyperkalemia is a life-threatening emergency in maintenance hemodialysis (MHD)
      patients. This clinical trial investigated the efficacy and safety of calcium
      polystyrene sulfonate (Ca-PS) in MHD patients with interdialytic hyperkalemia. A
      total of 58 hemodialysis patients with hyperkalemia (>=5.5 mol/L) were selected
      and administered either a 3-week Ca-PS (3 * 5 g/day) or a blank control following
      the model of a prospective, randomized, crossover clinical trial with a 1-week
      washout period. All patients were followed up for another 3 weeks for safety
      evaluations. The primary outcome was the magnitude of the change in serum
      potassium levels. The secondary outcomes were electrocardiography (ECG) changes
      and treatment safety (volume overload, electrolyte imbalance). Compared with the
      control group, Ca-PS treatment significantly reduced serum potassium levels (P
      <0.01). More patients in the Ca-PS group had lower serum potassium levels than
      the safety level of <5.5 mmol/L (32% for control vs. 61% for Ca-PS, P <0.01).
      Peaked T-wave occurred less frequently in patients in the Ca-PS group (13.8% for
      Ca-PS vs. 31.03% for control, P <0.01). In addition, Ca-PS reduced serum
      phosphorus levels with no effects on serum levels of calcium and sodium, fluid
      volume, blood pressure, or interdialytic weight gain. Ca-PS treatment decreases
      serum levels of potassium and phosphorus in MHD patients with interdialytic
      hyperkalemia. Ca-PS does not induce volume overload or disrupt electrolyte
      balance.

PMID- 30109785
TI  - Bioluminescence and chemiluminescence abilities of trans-3-hydroxyhispidin on the
      luminous fungus Mycena chlorophos.
AB  - The fungus Mycena chlorophos emits green light from its pileus gills but not from
      its stipes. The chemical mechanisms underlying its bioluminescence are unclear.
      Trans-3-hydroxyhispidin has been known to be a luminescence substrate for the
      bioluminescent mycelia of Neonothopanus nambi and N. gardneri. In the present
      study, the bioluminescence and chemiluminescence abilities of trans-3
      hydroxyhispidin on pileus gills and originally non-bioluminescent stipes of M.
      chlorophos were demonstrated. Trans-3-hydroxyhispidin induced bioluminescence of
      living gills and stipes. The bioluminescence spectra of living gills and stipes
      measured after the addition of trans-3-hydroxyhispidin were consistent with the
      original bioluminescence spectrum of gills. Frozen-thawed (dead) gills and stipes
      maintained trans-3-hydroxyhispidin luminescence activity, and the luminescence
      active enzyme (luciferase) was partially purified in the water-insoluble state
      from both tissues using gel filtration followed by ultracentrifugation. The
      optimum temperature of the chemiluminescence reactions of trans-3-hydroxyhispidin
      in the presence of partially purified gill or stipe luciferase was 25 degrees C.
      The chemiluminescence quantum yields of trans-3-hydroxyhispidin for gill
      luciferase and stipe luciferase in 20 mM phosphate buffer at 25 degrees C were
      0.017 and 0.00096, respectively and the chemiluminescence spectra were almost
      consistent with the bioluminescence spectrum of living gills. These results
      indicate that trans-3-hydroxyhispidin can be a candidate as a substrate for M.
      chlorophos bioluminescence.

PMID- 30109783
TI  - Characterization and drug sensitivity of a novel human ovarian clear cell
      carcinoma cell line genomically and phenotypically similar to the original tumor.
AB  - NUCOLL43 is a novel ovarian clear cell carcinoma (O-CCC) cell line that arose
      from a primary culture of a patient's malignant ascites. The cells grow reliably
      in cell culture with a doubling time of approx. 45 hours and form colonies at
      high efficiency. They have a very high degree of loss of heterozygosity (LOH)
      affecting approximately 85% of the genome, mostly copy neutral and almost
      identical to the original tumor. The cells express epithelial (pan-cytokeratin)
      and mesenchymal (vimentin) characteristics, CA125 and p16, like the original
      tumor. They also express ARID1A but not HNF-1beta and, like the original tumor,
      and are negative for p53 expression, with no evidence of p53 function. NUCOLL43
      cells express all other DNA damage response proteins investigated and have
      functional homologous recombination DNA repair. They are insensitive to
      cisplatin, the PARP inhibitor rucaparib, and MDM2 inhibitors but are sensitive to
      camptothecin, paclitaxel, and NVP-BEZ235. The NUCOLL43 cell line represents a
      distinct subtype of O-CCC that is p53 and HNF-1beta null but expresses ARID1A.
      Its high degree of similarity with the original tumor genomically and
      proteomically, as well as the high level of LOH, make this an interesting cell
      line for O-CCC research. It has been deposited with Ximbio.

PMID- 30109786
TI  - Correlations Between Core Needle Biopsy and Excisional Biopsy Findings in
      Suspected Breast Lesions: A Single Center Study.
AB  - BACKGROUND: When a breast lesion is suspected based on a physical exam,
      mammography, or ultrasound, a stereotactic core needle biopsy (CNB) is usually
      performed to help establish a definitive diagnosis. CNBs are far less invasive
      than excisional biopsies, with no need for general anesthetics or
      hospitalization, and no recovery period. However, since only samples of the mass
      are removed in a CNB and not the whole mass, sampling errors can occur.
      OBJECTIVES: To compare the degree of agreement between the pathological data from
      CNBs and excisional biopsies from a single tertiary referral hospital. METHODS:
      The concordance of pathological data was compared in patients who underwent CNBs
      and had their surgical procedures at the same medical center. RESULTS: From the
      894 patients who underwent CNBs, 254 (28.4%) underwent subsequent excisional
      biopsies at our medical center. From the total of 894 patients, 227 (25.3%) who
      underwent a CNB were diagnosed with a malignancy, with the rest of the CNBs being
      diagnosed as benign pathologies. The pathological findings in the CNBs and in the
      excisional biopsies concurred in 232/254 (91.3%) of the cases. CONCLUSIONS: A CNB
      to confirm mammographic or clinical findings of breast lesions is an accurate
      method to establish a pathological diagnosis of breast lesions. The accuracy is
      higher for invasive carcinomas than for non-invasive cancers. Excisional biopsies
      are necessary for lesions with anticipated sampling errors or when the core
      needle biopsy findings are discordant with clinical or mammographic findings.

PMID- 30109787
TI  - Anemia Management among Hemodialysis Patients with High Ferritin Levels.
AB  - BACKGROUND: Anemia management strategies among chronic hemodialysis patients with
      high ferritin levels remains challenging for nephrologists. OBJECTIVES: To
      compare anemia management in stable hemodialysis patients with high (>= 500
      ng/ml) vs. low (< 500 ng/ml) ferritin levels. METHODS: In a single center, record
      review, cohort study of stable hemodialysis patients who were followed for 24
      months, an anemia management policy was amended to discontinue intravenous (IV)
      iron therapy for stable hemodialysis patients with hemoglobin > 10 g/dl and
      ferritin >= 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses,
      and laboratory parameters were compared among patients with high vs. low baseline
      ferritin levels before and after IV iron cessation. RESULTS: Among 87 patients,
      73.6% had baseline ferritin >= 500 ng/ml. Weekly ESA dose was greater among
      patients with high vs. low ferritin (6788.8 +/- 4727.8 IU/week vs. 3305.0 +/-
      2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were
      significantly lower (1628.2 +/- 1491.1 mg vs. 2557.4 +/- 1398.9 mg, P = 0.011,
      and 82.9 +/- 85 vs. 140.7 +/- 63.9 mg, P = 0.004). Among patients with high
      ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%)
      and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change
      significantly during this period. CONCLUSIONS: Iron cessation in chronic
      hemodialysis patients with high ferritin levels did not affect hemoglobin level
      or ESA dose and can be considered as a safe policy for attenuating the risk of
      chronic iron overload.

PMID- 30109788
TI  - Achieving the Recommended Gestational Weight Gain in High-Risk Versus Low-Risk
      Pregnancies.
AB  - BACKGROUND: Abnormal gestational weight gain (GWG) has been associated with
      adverse outcomes for mothers and their offspring. OBJECTIVES: To compare the
      achievement of recommended GWG and lifestyle factors in women with high-risk
      versus normal-risk pregnancies. METHODS: Pregnant women hospitalized in a
      gynecological and obstetrics department and pregnant women who arrived at a
      community clinic for a routine checkup were interviewed and completed
      questionnaires relating to weight gain and lifestyle factors (e.g., smoking,
      diet, exercise). Recommended GWG was defined by the American Congress of
      Obstetricians and Gynecologists (ACOG). RESULTS: GWG higher than ACOG
      recommendations was reported by 52/92 women (57%) with normal pregnancies and by
      43/86 (50%) with high-risk pregnancies. On univariate analysis, characteristics
      associated with greater GWG were: current or past smoking, age > 40 years, pre
      gestational body mass index (BMI) > 25 kg/m2, low fruit intake, and high snack
      intake. High-risk pregnancies were associated with pre-gestational BMI > 25 kg/m2
      (48% vs. 27%, P = 0.012), consumption of vitamins (84% vs. 63%, P = 0.001),
      avoidance of certain foods (54% vs. 21%, P = 0.015), receiving professional
      nutritionist consultation (65% vs. 11%, P = 0.001), and less physical activity
      (9% vs. 24%, P = 0.01). CONCLUSIONS: A minority of pregnant women met the
      recommended GWG. No difference was noted between normal and high-risk
      pregnancies. High-risk population tended to have a less healthy lifestyle.
      Counseling to follow a healthy, balanced diet should be recommended, regardless
      of pregnancy risk, with particular attention to women at high risk of extra
      weight gain.

PMID- 30109789
TI  - Volumetric Modulated Arc Therapy as an Example of the Advanced Capability of
      Modern Radiotherapy.
AB  - BACKGROUND: Family physicians and internal medicine specialists play an essential
      role in treating cancer patients. Modern technological advances in radiotherapy
      are not widely appreciated by primary care physicians. Bone metastases are a
      frequent complication of cancer. Palliative radiation therapy, as a component of
      modern advances in radiation treatments, should not subject normal bodily
      structures to excessive doses of irradiation. The sacrum is a common destination
      site for bone metastases, yet its concave shape along with its proximity to the
      rectum, intestines, and femoral heads creates treatment-planning challenges.
      OBJECTIVES: To investigated whether the volumetric modulated arc therapy (VMAT)
      technique is preferable to more conventional radiation strategies. METHODS: The
      study comprised 22 patients with sacral metastases who were consecutively treated
      between 2013 and 2014. Two plans were generated for the comparison: three
      dimensional (3D) and VMAT. RESULTS: The planning target volume (PTV) coverage of
      the sacrum was identical in VMAT and 3D planning. The median values for the
      rectal dose for 3D and VMAT were 11.34 +/- 5.14 Gy and 7.7 +/- 2.76 Gy,
      respectively. Distal sacral involvement (S4 and S5) was observed in only 2 of 22
      cases, while the upper pole of the rectum ended at the level above S3 in just 3
      cases. CONCLUSIONS: Radiation therapy continues to be an integral component of
      the palliative armamentarium against painful metastases. Radiation oncologist, in
      conjunction with referral physicians, can tailor treatment plans to reflect the
      needs of a given patient.

PMID- 30109791
TI  - Clinical and Echocardiographic Outcomes after Aortic Valve Repair in Patients
      with Bicuspid or Unicuspid Aortic Valve.
AB  - BACKGROUND: Unicuspid and bicuspid aortic valve (BAV) are congenital cardiac
      anomalies associated with valvular dysfunction and aortopathies occurring at a
      young age. OBJECTIVES: To evaluate our experience with aortic valve repair (AVr)
      in patients with bicuspid or unicuspid aortic valves. METHODS: Eighty patients
      with BAV or unicuspid aortic valve (UAV) underwent AVr. Mean patient age was 42
      +/- 14 years and 94% were male. Surgical technique included: aortic root
      replacement with or without cusp repair in 43 patients (53%), replacement of the
      ascending aorta at the height of the sino-tubular junction with or without cusp
      repair in 15 patients (19%), and isolated cusp repair in 22 patients (28%).
      RESULTS: The anatomical structure of the aortic valve was bicuspid in 68 (85%)
      and unicuspid in 12 patients (15%). Survival rate was 100% at 5 years of follow
      up. Eleven patients (13.7%) underwent reoperation, 8 of whom presented with
      recurrent symptomatic aortic insufficiency (AI). Late echocardiography in the
      remaining 69 patients revealed mild AI in 63 patients, moderate recurrent AI in
      4, and severe recurrent AI in 2. Relief from recurrent severe AI or reoperations
      was significantly lower in patients who underwent cusp repair compared with those
      who did not (P = 0.05). Furthermore, the use of pericardial patch augmentation
      for the repair was a predictor for recurrence (P = 0.05). CONCLUSIONS: AVr in
      patients with BAV or UAV is a safe procedure with low morbidity and mortality
      rates. The use of a pericardial patch augmentation was associated with higher
      repair failure.

PMID- 30109790
TI  - The Association Between the Risk Scores for Cardiovascular Disease and Long-Term
      Mortality Following an Acute Coronary Event.
AB  - BACKGROUND: A patient's individual chance of being diagnosed with cardiovascular
      disease can be determined by risk scores. OBJECTIVES: To determine the risk score
      profiles of patients presenting with a first acute coronary event according to
      pre-admission risk factors and to evaluate its association with long-term
      mortality. METHODS: The research was based on a retrospective study of a cohort
      from the 2010 and 2013 Acute Coronary Syndrome Israeli Surveys (ACSIS). Inclusion
      criteria included first event and no history of coronary heart disease or
      cardiovascular disease risk equivalent. The Framingham Risk Score, the European
      Systematic COronary Risk Evaluation (SCORE), and the American College of
      Cardiology/American Heart Association/ (ACC/AHA) risk calculator were computed
      for each patient. The risk profile of each patients was determined by the three
      scores. The prognostic value of each score for 5 year survival was evaluated.
      RESULTS: The study population comprised 1338 patients enrolled in the prospective
      ACSIS survey. The ACC/AHA score was the most accurate in identifying patients as
      high risk based on pre-admission risk factors (73% of the subjects). The
      Framingham algorithm identified 53%, whereas SCORE recognized only 4%. After
      multivariate adjustment for clinical factors at presentation, we found that no
      scores were independently associated with 5 year mortality following the first
      acute coronary event. CONCLUSIONS: Patients with first acute coronary event had a
      higher pre-admission risk scores according to the ACC/AHA risk algorithm. No risk
      scores were independently associated with 5 year survival after an event.

PMID- 30109792
TI  - Successful Treatment of Extremely Severe Obstructive Sleep Apnea with a Dental
      Appliance.
AB  - BACKGROUND: A dental appliance for obstructive sleep apnea (OSA) is recommended
      for patients who cannot adjust to continuous positive airway pressure (CPAP)
      treatments. OBJECTIVES: To describe patients with extremely severe OSA who were
      successfully treated with a dental appliance and to compare their characteristics
      with the relevant literature to identify clinical features associated with a good
      outcome. METHODS: The clinical, management, and outcome data of three patients
      with an apnea-hypopnea index (AHI) of > 80 who showed clinical improvement
      following treatment with a dental appliance were collected retrospectively from
      sleep laboratory reports in Israel over a period of 3 years. RESULTS: The
      patients included one man and two women, aged 33, 56, and 61 years, respectively.
      The diagnosis of OSA was based on clinical examination and polysomnography. AHI
      values at presentation were 83, 81, and 84, respectively. Treatment with a dental
      appliance (Herbst(r) or MDSA(r)) was proposed due to patient noncompliance with
      CPAP. Follow-up polysomnography with the dental appliance revealed a reduction in
      the AHI to 1.7, 10.7, and 11, respectively. All patients had supine OSA and a
      retrognathic mandible, both of which have been found to be associated with a good
      prognosis for treatment with a dental appliance. CONCLUSIONS: Dental appliances
      may be considered an appropriate second-choice option to treat severe OSA in
      patients who are noncompliant with CPAP. This study helps physicians identify
      patients with extremely severe OSA who are suitable for dental appliance
      treatment. Well-designed large-scale studies are needed to reach definitive
      conclusions.

PMID- 30109793
TI  - Bloodstream Infections Caused by Contaminants: Epidemiology and Risk Factors: A
      10-Year Surveillance.
AB  - BACKGROUND: Skin colonization of microorganisms in blood cultures (BCs) are
      generally considered clinically non-significant and can be the source of a true
      infection, particularly in immunosuppressed patients. OBJECTIVES: To study the
      epidemiology and risk factors for bacteremia caused by contaminants. METHODS:
      This retrospective, descriptive study is based on adult BCs collected (2004-2013)
      and categorized as positive (True bacteremia [TrueB] or contamination) or
      negative. Clinical, demographic, and laboratory characteristics of BCs positive
      for the six most common potential contaminant pathogens (PCPs) that can cause
      TrueB and contamination (Coagulase-negative Staphylococcus [CoNS], Streptococcus
      viridans, Propionibacterium acnes, Corynebacterium spp., Bacillus spp.,
      Clostridium spp.) were assessed. Ninety-two TrueB were identified vs. 196
      contaminations (1:2 ratio). RESULTS: From 74,014 BCs, PCPs were found in 3735
      samples, of which 3643 (97.5%) were contaminations and 92 (2.5%) were TrueB. The
      overall rate of BC contamination decreased during the study period from 6.7% to
      3.8%. CoNS was the most common PCP. Bacillus spp. were only contaminants.
      Clostridium spp. and Streptococcus viridans were more often TrueB. In a
      multivariate model, predictors of TrueB included high creatinine levels,
      Streptococcus viridans in BC, and multiple positive BCs. A single culture of CoNS
      was strongly predictive of contamination. CONCLUSIONS: Ten years of data on BCs,
      focusing on six PCPs, demonstrates a significant, yet insufficient reduction in
      the rate of contamination. High creatinine level, isolation of Streptococcus
      viridans, and multiple positive BCs were predictors of TrueB, while growth of
      CoNS was strongly predictive of contamination. This model could assist in
      diagnostic and therapeutic decision making.

PMID- 30109794
TI  - Prompt Clinical Response to Secukinumab in Patients with Axial Spondyloarthritis:
      Real Life Observational Data from Three Italian Referral Centers.
AB  - BACKGROUND: Clinical research is needed to identify patients with axial
      spondyloarthritis (axSpA) who are more likely to be responsive to interleukin
      (IL)-17 inhibition. OBJECTIVES: To evaluate short-term efficacy of secukinumab in
      the management of axSpA. METHODS: Twenty-one patients (7 males, 14 females) with
      axSpA were consecutively treated with secukinumab. Laboratory and clinical
      assessments were based on erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, and
      Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Data were recorded
      at baseline and at a 3 month follow-up visit. RESULTS: The study was comprised of
      21 patients. Both BASDAI and ASDAS-CRP showed a statistically significant
      reduction between the baseline and the 3 month visit (P < 0.0001 and P = 0.0005,
      respectively). During the laboratory assessment, ESR showed a significant
      decrease (P = 0.008) while CRP improvement did not reach statistical significance
      (P = 0.213). No statistical significance was observed between patients treated
      with secukinumab 150 mg vs. 300 mg in BASDAI (P=0.99), ASDAS-CRP (P = 0.69), ESR
      (P = 0.54), and CRP (P = 0.56). No significant differences emerged between the
      BASDAI (P = 0.15), ASDAS-CRP (P = 0.09), and CRP (P = 0.15) rates in biologic
      naive patients and those previously failing tumor necrosis factor-alpha
      inhibition. Conversely, ESR decrease was significantly higher in the biologic
      naive subgroup (P = 0.01). No adverse events were reported. CONCLUSIONS:
      Secukinumab has proven remarkable short-term effectiveness, regardless of the
      biologic treatment line. A dosage of 150 mg proved to be appropriate in the
      clinical and laboratory management of axSpA.

PMID- 30109795
TI  - Outcomes of French's Corrective Osteotomy of the Humerus for Cubitus Varus
      Deformity in Children.
AB  - BACKGROUND: Supracondylar humerus fractures are the most common elbow fractures
      in the pediatric population. OBJECTIVES: To evaluate the outcomes of French's
      corrective osteotomy for correction of post-traumatic cubitus varus deformity in
      children. METHODS: We conducted a retrospective review of medical charts of all
      patients who had undergone French's corrective osteotomy in our institution from
      1998 to 2012. We recorded range of motion, cosmetic deformity, carrying angle,
      lateral cortex prominence index, hyperextension, and lateral cortex step before
      and after the surgery. RESULTS: Seven patients were enrolled the study. Average
      follow-up time was 4.6 years (range 2-9 years). An average of 18.3o of limited
      flexion (range 5o-35o) compared to the healthy elbow was recorded in three
      patients. Lateral condylar prominence was recorded in one patient. The average
      preoperative carrying angle was -20.5o (range -15o-30o) and postoperative angle
      was 9.6o (range 7o-13o). In comparison, the average carrying angle in the healthy
      elbow was 8.5o (range 4o-13o). No lateral cortex prominence was recorded. An
      average of 27.5o (range 15o-35o) of hyperextension of the distal fragment was
      recorded immediately postoperatively in four patients; however, during
      postoperative follow-up, the hyperextension was corrected spontaneously in all
      patients. CONCLUSIONS: As described by French, osteotomy has the ability to
      correct the varus deformity only in the coronal plane. However, our research
      supports the assumption that hyperextension in the sagittal plane might be
      corrected spontaneously.

PMID- 30109796
TI  - Digital Ischemia in a Patient with Recent Influenza A Infection.

PMID- 30109797
TI  - Lemierre's Syndrome in an Aseptic Patient with Systemic Lupus Erythematosus.

PMID- 30109798
TI  - Balloon Expandable Covered Stent in a Child with Traumatic Aortic Rupture.

PMID- 30109799
TI  - Childhood Limb Poliomyelitis as a Suspected Etiology for a Contra-Lateral Femoral
      Arteriomegaly and Aneurysm Formation.

PMID- 30109800
TI  - Delusional Parasitosis: Diagnosis and Treatment.
AB  - BACKGROUND: Delusional parasitosis (DP) is a somatic type of delusional disorder,
      usually mono-symptomatic, in which the patients are convinced they are being
      infested with animal parasites while no objective evidence exists to support this
      belief. The complaints are usually about skin infestation, but involvement of the
      gastrointestinal tract has also been described. Numerous samples are brought for
      examination from skin, clothes, and environmental sources, while a detailed
      description of the "parasite" is given. In primary DP, the delusion arises
      spontaneously as a mono-delusional disorder, while in secondary DP, the
      delusional disorder arises secondary to another major medical, neurological, or
      psychiatric disorder. Practically all patients refuse psychiatric help. Shared
      psychotic disorder - folie a deux - is a known mode of presentation in delusional
      parasitosis. More than one member within a family may experience the same
      delusional state. For diagnosis and treatment of DP, a close collaboration among
      dermatologists, psychiatrists, and parasitologists is essential. Patients whose
      delusion of parasitosis is not severe can sometimes be relieved of their symptoms
      by establishing a reliable and meaningful therapeutic relationship. Symptomatic
      medication may be prescribed for the relief of pruritus, pain, and other
      symptoms. In more severe cases, such patients should be treated with
      psychopharmacological agents.

PMID- 30109801
TI  - Combined Gastric and Pancreatic Tissue Inside a Meckel's Diverticulum.

PMID- 30109802
TI  - Reconstruction method for fluorescence molecular tomography based on L1-norm
      primal accelerated proximal gradient.
AB  - Fluorescence molecular tomography (FMT) has been widely used in preclinical tumor
      imaging, which enables three-dimensional imaging of the distribution of
      fluorescent probes in small animal bodies via image reconstruction method.
      However, the reconstruction results are usually unsatisfactory in the term of
      robustness and efficiency because of the ill-posed and ill-conditioned of FMT
      problem. In this study, an FMT reconstruction method based on primal accelerated
      proximal gradient (PAPG) descent and L1-norm regularized projection (L1RP) is
      proposed. The proposed method utilizes the current and previous iterations to
      obtain a search point at each iteration. To achieve fast convergence, the PAPG
      method is applied to efficiently solve the search point, and then L1RP is
      performed to obtain the robust and accurate reconstruction. To verify the
      performance of the proposed method, simulation experiments are conducted. The
      comparative results revealed that it held advantages of robustness, accuracy, and
      efficiency in FMT reconstructions. Furthermore, a phantom experiment and an in
      vivo mouse experiment were also performed, which proved the potential and
      feasibility of the proposed method for practical applications.

PMID- 30109803
TI  - Anti-inflammatory Potential of Flavonoids from the Aerial Parts of Corispermum
      marschallii.
AB  - The isolation of phenolics from aerial parts of Corispermum marschallii yielded a
      total of 13 compounds including nine previously undescribed patuletin and
      spinacetin glycosides. These were identified as patuletin 3- O-beta-d
      galactopyranosyl-7- O-beta-d-glucopyranoside (1), spinacetin 3- O-beta-d
      galactopyranosyl-7- O-beta-d-glucopyranoside (2), patuletin 3- O-(6"- O-beta-d
      glucopyranosyl)-beta-d-galactopyranoside (3), patuletin 3- O-(6"- O-alpha-l
      arabinopyranosyl)-beta-d-galactopyranoside (4), patuletin 3- O-(2"- O-(5'''- O
      alpha-l-arabinopyranosyl)-beta-d-apiofuranosyl)-beta-d-galactopyranoside (5),
      patuletin 3- O-(2"- O-beta-d-apiofuranosyl)-beta-d-galactopyranoside (6),
      spinacetin 3- O-beta-d-galactopyranoside (7), patuletin 3- O-beta-d
      galactopyranosyl-7- O-(6'''- O-feruloyl)-beta-d-glucopyranoside (8), and
      spinacetin 3- O-beta-d-galactopyranosyl-7- O-(6'''- O-feruloyl)-beta-d
      glucopyranoside (9). Structure elucidation was based on UV-visible, multistage
      MS, and 1D and 2D NMR spectroscopy and chemical derivatization, which allowed the
      identification on the glycosides with two different hexose moieties occurring at
      different positions of the aglycones. Most of the compounds tested inhibited the
      production of pro-inflammatory factors such as ROS, IL-8, and TNF-alpha in
      stimulated neutrophils.

PMID- 30109804
TI  - In Situ Strain Tuning of the Dirac Surface States in Bi2Se3 Films.
AB  - Elastic strain has the potential for a controlled manipulation of the band gap
      and spin-polarized Dirac states of topological materials, which can lead to
      pseudomagnetic field effects, helical flat bands, and topological phase
      transitions. However, practical realization of these exotic phenomena is
      challenging and yet to be achieved. Here we show that the Dirac surface states of
      the topological insulator Bi2Se3 can be reversibly tuned by an externally applied
      elastic strain. Performing in situ X-ray diffraction and in situ angle-resolved
      photoemission spectroscopy measurements during tensile testing of epitaxial
      Bi2Se3 films bonded onto a flexible substrate, we demonstrate elastic strains of
      up to 2.1% and quantify the resulting changes in the topological surface state.
      Our study establishes the functional relationship between the lattice and
      electronic structures of Bi2Se3 and, more generally, demonstrates a new route
      toward momentum-resolved mapping of strain-induced band structure changes.

PMID- 30109805
TI  - Electrochemical Tuning of Metal Insulator Transition and Nonvolatile Resistive
      Switching in Superconducting Films.
AB  - Modulation of carrier concentration in strongly correlated oxides offers the
      unique opportunity to induce different phases in the same material, which
      dramatically change their physical properties, providing novel concepts in oxide
      electronic devices with engineered functionalities. This work reports on the
      electric manipulation of the superconducting to insulator phase transition in
      YBa2Cu3O7-delta thin films by electrochemical oxygen doping. Both normal state
      resistance and the superconducting critical temperature can be reversibly
      manipulated in confined active volumes of the film by gate-tunable oxygen
      diffusion. Vertical and lateral oxygen mobility may be finely modulated, at the
      micro- and nano-scale, by tuning the applied bias voltage and operating
      temperature thus providing the basis for the design of homogeneous and flexible
      transistor-like devices with loss-less superconducting drain-source channels. We
      analyze the experimental results in light of a theoretical model, which
      incorporates thermally activated and electrically driven volume oxygen diffusion.

PMID- 30109806
TI  - Nanoserpents: Graphene Nanoribbon Motion on Two-Dimensional Hexagonal Materials.
AB  - We demonstrate snake-like motion of graphene nanoribbons atop graphene and
      hexagonal boron nitride ( h-BN) substrates using fully atomistic nonequilibrium
      molecular dynamics simulations. The sliding dynamics of the edge-pulled
      nanoribbons is found to be determined by the interplay between in-plane ribbon
      elasticity and interfacial lattice mismatch. This results in an unusual
      dependence of the friction-force on the ribbon's length, exhibiting an initial
      linear rise that levels-off above a junction-dependent threshold value dictated
      by the pre-slip stress distribution within the slider. As part of this letter, we
      present the LAMMPS implementation of the registry-dependent interlayer potentials
      for graphene, h-BN, and their heterojunctions that were used herein, which
      provides enhanced performance and accuracy.

PMID- 30109807
TI  - Proteomics Goes to Court: A Statistical Foundation for Forensic Toxin/Organism
      Identification Using Bottom-Up Proteomics.
AB  - Bottom-up proteomics is increasingly being used to characterize unknown
      environmental, clinical, and forensic samples. Proteomics-based bacterial
      identification typically proceeds by tabulating peptide "hits" (i.e., confidently
      identified peptides) associated with the organisms in a database; those organisms
      with enough hits are declared present in the sample. This approach has proven to
      be successful in laboratory studies; however, important research gaps remain.
      First, the common-practice reliance on unique peptides for identification is
      susceptible to a phenomenon known as signal erosion. Second, no general
      guidelines are available for determining how many hits are needed to make a
      confident identification. These gaps inhibit the transition of this approach to
      real-world forensic samples where conditions vary and large databases may be
      needed. In this work, we propose statistical criteria that overcome the problem
      of signal erosion and can be applied regardless of the sample quality or data
      analysis pipeline. These criteria are straightforward, producing a p-value on the
      result of an organism or toxin identification. We test the proposed criteria on
      919 LC-MS/MS data sets originating from 2 toxins and 32 bacterial strains
      acquired using multiple data collection platforms. Results reveal a > 95% correct
      species-level identification rate, demonstrating the effectiveness and robustness
      of proteomics-based organism/toxin identification.

PMID- 30109809
TI  - The upregulation of hypoxia-related miRNA 210 in primary tumor of lymphogenic
      metastatic prostate cancer.
AB  - AIM: To show the association between the expression level of hsa-miR-210 (miR
      210) and tumor progression in prostate cancer (PCa). METHODS: Quantitative PCR
      was performed to measure miR-210 on 55 subjects with different tumor stages; our
      results were then validated using three external datasets. ANOVA and Tukey's post
      hoc analysis were performed for comparative analyses between different tumor
      stages. Using the transcriptome data from The Cancer Genome Atlas for CaP, the
      gene expression analyses were performed on experimentally validated target genes
      of miR-210 identified in Tarbase and miRWalk datasets. RESULTS & CONCLUSION: miR
      210 was significantly higher in N1 PCa compared with nonmetastatic PCa, whereas
      the metastatic tumor revealed a lower expression level of miR-210 than the
      primary tumor.

PMID- 30109808
TI  - Nanoscale Functionalized Particles with Rotation-Controlled Capture in Shear
      Flow.
AB  - Important processes in nature and technology involve the adhesive capture of
      flowing particles or cells on the walls of a conduit. This paper introduces
      engineered spherical microparticles whose capture rates are limited by their near
      surface motions in flow. Specifically, these microparticles are sparsely
      functionalized with nanoscopic regions ("patches") of adhesive functionality,
      without which they would be nonadhesive. Not only is particle capture on the wall
      of a shear-chamber limited by surface chemistry as opposed to transport, but also
      the capture rates depend specifically on particle rotations that result from the
      vorticity of the shear flow field. These particle rotations continually expose
      new particle surface to the opposing chamber wall, sampling the particle surface
      for an adhesive region and controlling the capture rate. Control studies with the
      same patchy functionality on the chamber wall rather than the particles reveal a
      related signature of particle capture but substantially faster (still surface
      limited) particle capture rates. Thus, when the same functionality is placed on
      the wall rather than the particles, the capture is faster because it depends on
      the particle translation past a functionalized wall rather than on the particle
      rotations. The dependence of particle capture on functionalization of the
      particles versus the wall is consistent with the faster near-wall particle
      translation in shearing flow compared with the velocity of the rotating particle
      surface near the wall. These findings, in addition to providing a new class of
      nanoscopically patchy engineered particles, provide insight into the capture and
      detection of cells presenting sparse distinguishing surface features and the
      design of delivery packages for highly targeted pharmaceutical delivery.

PMID- 30109810
TI  - Fitting an Optical Fiber Background with a Weighted Savitzky-Golay Smoothing
      Filter for Raman Spectroscopy.
AB  - The Raman background arising from optical fiber materials poses a critical
      problem for fiber optic surface-enhanced Raman spectroscopy (SERS). A novel
      filter is developed to fit the optical fiber background from the measured SERS
      spectrum of the target sample. The general model of the filter is built by
      incorporating a weighted term of matching the similarity between the estimated
      background spectrum and the measured background spectrum into the classic
      Savitzky-Golay (SG) smoothing filter model. Through respectively selecting
      Euclidean cosine coefficient (ECos) and Pearson correlation coefficient (PCor) as
      the similarity index, two different models of the weighted SG smoothing filter
      are derived and named as SG-ECos and SG-PCor accordingly. Furthermore, the
      algorithm is presented, implemented, successfully applied to experimentally
      measured SERS spectra of rhodamine 6G and crystal violet, and validated with
      mathematically simulated Raman spectra. Experimental and simulation results show
      that the SG-ECos filter is effective, fast, flexible, and of certain anti-noise
      capability in background fitting. It is suggested that the proposed filter may be
      also applicable for other Raman spectra measurements to remove spectral
      contaminants originated from sampling substrates such as glass slides.

PMID- 30109811
TI  - The pro-oxidant adaptor p66SHC promotes B cell mitophagy by disrupting
      mitochondrial integrity and recruiting LC3-II.
AB  - Macroautophagy/autophagy has emerged as a central process in lymphocyte
      homeostasis, activation and differentiation. Based on our finding that the p66
      isoform of SHC1 (p66SHC) pro-apoptotic ROS-elevating SHC family adaptor inhibits
      MTOR signaling in these cells, here we investigated the role of p66SHC in B-cell
      autophagy. We show that p66SHC disrupts mitochondrial function through its CYCS
      (cytochrome c, somatic) binding domain, thereby impairing ATP production, which
      results in AMPK activation and enhanced autophagic flux. While p66SHC binding to
      CYCS is sufficient for triggering apoptosis, p66SHC-mediated autophagy
      additionally depends on its ability to interact with membrane-associated LC3-II
      through a specific binding motif within its N terminus. Importantly, p66SHC also
      has an impact on mitochondria homeostasis by inducing mitochondrial
      depolarization, protein ubiquitination at the outer mitochondrial membrane, and
      local recruitment of active AMPK. These events initiate mitophagy, whose full
      execution relies on the role of p66SHC as an LC3-II receptor which brings
      phagophore membranes to mitochondria. Importantly, p66SHC also promotes hypoxia
      induced mitophagy in B cells. Moreover, p66SHC deficiency enhances B cell
      differentiation to plasma cells, which is controlled by intracellular ROS levels
      and the hypoxic germinal center environment. The results identify mitochondrial
      p66SHC as a novel regulator of autophagy and mitophagy in B cells and implicate
      p66SHC-mediated coordination of autophagy and apoptosis in B cell survival and
      differentiation. Abbreviations: ACTB: actin beta; AMPK: AMP-activated protein
      kinase; ATP: adenosine triphosphate; ATG: autophagy-related; CYCS: cytochrome c,
      somatic; CLQ: chloroquine; COX: cyclooxygenase; CTR: control; GFP: green
      fluorescent protein; HIFIA/Hif alpha: hypoxia inducible factor 1 subunit alpha;
      IMS: intermembrane space; LIR: LC3 interacting region; MAP1LC3B/LC3B: microtubule
      associated protein 1 light chain 3 beta; MTOR/mTOR: mechanistic target of
      rapamycin kinase; OA: oligomycin and antimycin A; OMM: outer mitochondrial
      membrane; PHB: prohibitin; PBS: phosphate-buffered saline; PINK1: PTEN induced
      putative kinase 1; RFP: red fluorescent protein; ROS: reactive oxygen species;
      SHC: src Homology 2 domain-containing transforming protein; TMRM:
      tetramethylrhodamine, methyl ester; TOMM: translocase of outer mitochondrial
      membrane; ULK1: unc-51 like autophagy activating kinase 1; WT: wild-type.

PMID- 30109814
TI  - Therapeutic hypothermia for moderate and severe hypoxic ischaemic encephalopathy
      in newborns using low-cost devices - ice packs and phase changing material.
AB  - BACKGROUND: Different methods have been used for therapeutic hypothermia for
      neonates with moderate-to-severe hypoxic ischaemic encephalopathy (HIE). As
      standard cooling devices are expensive, there is a need to establish the safety
      and efficacy of low-cost devices such as ice packs (IP) and phase changing
      material (PCM). AIM: To assess the efficacy and safety of therapeutic hypothermia
      (TH) and the clinico-laboratory profile of neonates who underwent cooling with IP
      or PCM. METHODS: The study was retrospective. TH for moderate-to-severe HIE was
      initiated with IP between 2012 and 2014 and with PCM (MiraCradleTM) from
      September 2014. A standard protocol for inclusion and management during TH was
      used for all newborns. All data were collected by means of a local cooling
      registry. RESULTS: Sixty-two cooled newborns (IP 29, PCM 33) were included in the
      study. Mean gestational age was 38.6 (1.7) weeks and mean birthweight 2920.6 g
      (450.7); 66.1% were inborn and 91.9% had moderate encephalopathy. Mean (SD) core
      temperature during cooling was 33.47 degrees C (0.33) for PCM and 33.44 degrees C
      (0.34) for IP. Adverse events observed during TH were thrombocytopenia (54.8%),
      coagulopathy (30.6%), shock (30.6%), skin changes (12.9%) and persistent
      pulmonary hypertension (8.1%). Forty-nine infants were discharged, two died and
      11 were discharged against medical advice. TH was prematurely stopped in seven
      newborns with serious adverse events such as disseminated intravascular
      coagulation (DIC), gangrene and arrhythmia (IP 5, PCM 2). CONCLUSION: Low-cost
      devices are safe and effective alternatives for maintaining TH in low-resource
      settings with adequate monitoring. ABBREVIATIONS: DAMA, discharged against
      medical advice; DIC, disseminated intravascular coagulation; HELIX, Hypothermia
      for Encephalopathy in Low- and Middle-Income Countries Trial; HIE, hypoxic
      ischaemic encephalopathy; IP, ice packs; LMIC, low- and middle-income countries;
      NICHD, National Institute of Child Health and Human Development; PCM, phase
      changing; TH, therapeutic hypothermia (TH); TOBY, total body hypothermia for
      neonatal encephalopathy.

PMID- 30109812
TI  - Novel isatin-derived molecules activate p53 via interference with Mdm2 to promote
      apoptosis.
AB  - The p53 protein is a key tumor suppressor in mammals. In response to various
      forms of genotoxic stress p53 stimulates expression of genes whose products
      induce cell cycle arrest and/or apoptosis. An E3-ubiquitin ligase, Mdm2 (mouse
      double-minute 2) and its human ortholog Hdm2, physically interact with the amino
      terminus of p53 to mediate its ubiquitin-mediated degradation via the proteasome.
      Thus, pharmacological inhibition of the p53-Mdm2 interaction leads to overall
      stabilization of p53 and stimulation of its anti-tumorigenic activity. In this
      study we characterize the biological effects of a novel class of non-genotoxic
      isatin Schiff and Mannich base derivatives (ISMBDs) that stabilize p53 on the
      protein level. The likely mechanism behind their positive effect on p53 is
      mediated via the competitive interaction with Mdm2. Importantly, unlike Nutlin,
      these compounds selectively promoted p53-mediated cell death. These novel
      pharmacological activators of p53 can serve as valuable molecular tools for
      probing p53-positive tumors and set up the stage for development of new anti
      cancer drugs.

PMID- 30109813
TI  - Regulation of IRE1 RNase activity by the Ribonuclease inhibitor 1 (RNH1).
AB  - Adaptation to endoplasmic reticulum (ER) stress depends on the activation of the
      sensor inositol-requiring enzyme 1alpha (IRE1), an endoribonuclease that splices
      the mRNA of the transcription factor XBP1 (X-box-binding protein 1). To better
      understand the protein network that regulates the activity of the IRE1 pathway,
      we systematically screened the proteins that interact with IRE1 and identified a
      ribonuclease inhibitor called ribonuclease/angiogenin inhibitor 1 (RNH1). RNH1 is
      a leucine-rich repeat domains-containing protein that binds to and inhibits
      ribonucleases. Immunoprecipitation experiments confirmed this interaction.
      Docking experiments indicated that RNH1 physically interacts with IRE1 through
      its cytosolic RNase domain. Upon ER stress, the interaction of RNH1 with IRE1 in
      the ER increased at the expense of the nuclear pool of RNH1. Inhibition of RNH1
      expression using siRNA mediated RNA interference upon ER stress led to an
      increased splicing activity of XBP1. Modulation of IRE1 RNase activity by RNH1
      was recapitulated in a cell-free system, suggesting direct regulation of IRE1 by
      RNH. We conclude that RNH1 attenuates the activity of IRE1 by interacting with
      its ribonuclease domain. These findings have implications for understanding the
      molecular mechanism by which IRE1 signaling is attenuated upon ER stress.

PMID- 30109815
TI  - PAM identification by CRISPR-Cas effector complexes: diversified mechanisms and
      structures.
AB  - Adaptive immunity of prokaryotes is mediated by CRISPR-Cas systems that employ a
      large variety of Cas protein effectors to identify and destroy foreign genetic
      material. The different targeting mechanisms of Cas proteins rely on the proper
      protection of the host genome sequence while allowing for efficient detection of
      target sequences, termed protospacers. A short DNA sequence, the protospacer
      adjacent motif (PAM), is frequently used to mark proper target sites. Cas
      proteins have evolved a multitude of PAM-interacting domains, which enables them
      to cope with viral anti-CRISPR measures that alter the sequence or accessibility
      of PAM elements. In this review, we summarize known PAM recognition strategies
      for all CRISPR-Cas types. Available structures of target bound Cas protein
      effector complexes highlight the diversity of mechanisms and domain architectures
      that are employed to guarantee target specificity.

PMID- 30109816
TI  - The Corticotropin-Releasing Factor Family: Physiology of the Stress Response.
AB  - The physiological stress response is responsible for the maintenance of
      homeostasis in the presence of real or perceived challenges. In this function,
      the brain activates adaptive responses that involve numerous neural circuits and
      effector molecules to adapt to the current and future demands. A maladaptive
      stress response has been linked to the etiology of a variety of disorders, such
      as anxiety and mood disorders, eating disorders, and the metabolic syndrome. The
      neuropeptide corticotropin-releasing factor (CRF) and its relatives, the
      urocortins 1-3, in concert with their receptors (CRFR1, CRFR2), have emerged as
      central components of the physiological stress response. This central peptidergic
      system impinges on a broad spectrum of physiological processes that are the basis
      for successful adaptation and concomitantly integrate autonomic, neuroendocrine,
      and behavioral stress responses. This review focuses on the physiology of CRF
      related peptides and their cognate receptors with the aim of providing a
      comprehensive up-to-date overview of the field. We describe the major molecular
      features covering aspects of gene expression and regulation, structural
      properties, and molecular interactions, as well as mechanisms of signal
      transduction and their surveillance. In addition, we discuss the large body of
      published experimental studies focusing on state-of-the-art genetic approaches
      with high temporal and spatial precision, which collectively aimed to dissect the
      contribution of CRF-related ligands and receptors to different levels of the
      stress response. We discuss the controversies in the field and unravel knowledge
      gaps that might pave the way for future research directions and open up novel
      opportunities for therapeutic intervention.

PMID- 30109818
TI  - Phosphate as a Signaling Molecule and Its Sensing Mechanism.
AB  - In mammals, phosphate balance is maintained by influx and efflux via the
      intestines, kidneys, bone, and soft tissue, which involves multiple
      sodium/phosphate (Na+/Pi) cotransporters, as well as regulation by several
      hormones. Alterations in the levels of extracellular phosphate exert effects on
      both skeletal and extra-skeletal tissues, and accumulating evidence has suggested
      that phosphate itself evokes signal transduction to regulate gene expression and
      cell behavior. Several in vitro studies have demonstrated that an elevation in
      extracellular Pi activates fibroblast growth factor receptor, Raf/MEK (mitogen
      activated protein kinase/ERK kinase)/ERK (extracellular signal-regulated kinase)
      pathway and Akt pathway, which might involve the type III Na+/Pi cotransporter
      PiT-1. Excessive phosphate loading can lead to various harmful effects by
      accelerating ectopic calcification, enhancing oxidative stress, and dysregulating
      signal transduction. The responsiveness of mammalian cells to altered
      extracellular phosphate levels suggests that they may sense and adapt to
      phosphate availability, although the precise mechanism for phosphate sensing in
      mammals remains unclear. Unicellular organisms, such as bacteria and yeast, use
      some types of Pi transporters and other molecules, such as kinases, to sense the
      environmental Pi availability. Multicellular animals may need to integrate
      signals from various organs to sense the phosphate levels as a whole organism,
      similarly to higher plants. Clarification of the phosphate-sensing mechanism in
      humans may lead to the development of new therapeutic strategies to prevent and
      treat diseases caused by phosphate imbalance.

PMID- 30109820
TI  - Physiology in Perspective: The Breath of Life.

PMID- 30109822
TI  - Monogenic Intestinal Epithelium Defects and the Development of Inflammatory Bowel
      Disease.
AB  - The incidence of inflammatory bowel disease (IBD) is increasing worldwide, most
      notably in young children. The development of disease is a combination of several
      factors, including genetics, environment, the microbiota, and immune system.
      Recently, next-generation sequencing has allowed for the identification of novel
      genetic causes for intestinal disease, including pediatric inflammatory bowel
      disease (IBD). These IBD genes can generally be grouped into genes causing either
      primary immunodeficiency or intestinal epithelial defects (the focus of this
      review). Most of these genes have been functionally validated with in vitro
      and/or animal models, and have been demonstrated to cause intestinal disease.
      Intestinal epithelial IBD genes are of particular interest since they are the
      least amenable to current therapies; therefore, further research is warranted to
      develop potential therapies. A number of cellular pathways are impacted with
      intestinal epithelial IBD genes, including intestinal epithelial cell adhesion
      and generation of reactive oxygen species. Here, we describe the currently known
      IBD risk alleles and monogenic causal intestinal epithelial genes, their putative
      roles in preserving intestinal epithelial cell homeostasis, and their
      implications for IBD pathophysiology.

PMID- 30109821
TI  - Oxidative Stress, Intrauterine Growth Restriction, and Developmental Programming
      of Type 2 Diabetes.
AB  - Intrauterine growth restriction (IUGR) leads to reduced birth weight and the
      development of metabolic diseases such as Type 2 diabetes in adulthood.
      Mitochondria dysfunction and oxidative stress are commonly found in key tissues
      (pancreatic islets, liver, and skeletal muscle) of IUGR individuals. In this
      review, we explore the role of oxidative stress in IUGR-associated diabetes
      etiology.

PMID- 30109819
TI  - Neuroimmune Communication in Health and Disease.
AB  - The immune and nervous systems are tightly integrated, with each system capable
      of influencing the other to respond to infectious or inflammatory perturbations
      of homeostasis. Recent studies demonstrating the ability of neural stimulation to
      significantly reduce the severity of immunopathology and consequently reduce
      mortality have led to a resurgence in the field of neuroimmunology. Highlighting
      the tight integration of the nervous and immune systems, afferent neurons can be
      activated by a diverse range of substances from bacterial-derived products to
      cytokines released by host cells. While activation of vagal afferents by these
      substances dominates the literature, additional sensory neurons are responsive as
      well. It is becoming increasingly clear that although the cholinergic anti
      inflammatory pathway has become the predominant model, a multitude of functional
      circuits exist through which neuronal messengers can influence immunological
      outcomes. These include pathways whereby efferent signaling occurs independent of
      the vagus nerve through sympathetic neurons. To receive input from the nervous
      system, immune cells including B and T cells, macrophages, and professional
      antigen presenting cells express specific neurotransmitter receptors that affect
      immune cell function. Specialized immune cell populations not only express
      neurotransmitter receptors, but express the enzymatic machinery required to
      produce neurotransmitters, such as acetylcholine, allowing them to act as
      signaling intermediaries. Although elegant experiments have begun to decipher
      some of these interactions, integration of these molecules, cells, and anatomy
      into defined neuroimmune circuits in health and disease is in its infancy. This
      review describes these circuits and highlights continued challenges and
      opportunities for the field.

PMID- 30109823
TI  - Defining the Rhythmogenic Elements of Mammalian Breathing.
AB  - Breathing's remarkable ability to adapt to changes in metabolic, environmental,
      and behavioral demands stems from a complex integration of its rhythm-generating
      network within the wider nervous system. Yet, this integration complicates
      identification of its specific rhythmogenic elements. Based on principles learned
      from smaller rhythmic networks of invertebrates, we define criteria that identify
      rhythmogenic elements of the mammalian breathing network and discuss how they
      interact to produce robust, dynamic breathing.

PMID- 30109824
TI  - The Neurobiological Basis of Sleep and Sleep Disorders.
AB  - The functions of sleep remain a mystery. Yet they must be important since sleep
      is highly conserved, and its chronic disruption is associated with various
      metabolic, psychiatric, and neurodegenerative disorders. This review will cover
      our evolving understanding of the mechanisms by which sleep is controlled and the
      complex relationship between sleep and disease states.

PMID- 30109825
TI  - Hypoxia Signaling in Vascular Homeostasis.
AB  - Hypoxia signaling in the vasculature controls vascular permeability,
      inflammation, vascular growth, and repair of vascular injury. In this review, we
      summarize recent insights in this burgeoning field and highlight the importance
      of studying the heterogeneity of hypoxia responses among individual patients,
      distinct vascular beds, and even individual vascular cells.

PMID- 30109827
TI  - Prevention of Cardiovascular Diseases with Anti-Inflammatory and Anti- Oxidant
      Nutraceuticals and Herbal Products: An Overview of Pre-Clinical and Clinical
      Studies.
AB  - BACKGROUND: Inflammation-induced endothelial abnormalities, dietary habits, and
      tobacco smoking are considered to be the primary risk factors for causing
      atherosclerosis and Cardiovascular Diseases (CVDs), including Coronary Heart
      Disease (CHD), cerebrovascular disorders, peripheral arterial disease, rheumatic
      heart disease, congenital heart defects, deep vein thrombosis and pulmonary
      embolism. Prevention of CVDs with anti-inflammatory and anti-oxidant agents has
      been a challenging task for decades. Currently, CVDs have taken a top position
      among the health-related issues and are considered the foremost cause of
      mortality and morbidity around the globe. OBJECTIVE: Emerging evidence from
      several sources indicates that nutraceuticals and plant products may be a cost
      effective approach for the prevention of CVDs. A limited number of clinical
      studies done with nutraceuticals have shown positive effects for promoting health
      and well-being as well as reduction of CVDs in humans. Some plants from which
      nutraceutical ingredients are isolated and will be discussed in this review are:
      Murraya koenigii, Curcuma longa, Beta vulgaris, Allium sativum, Allium cepa,
      Lagenaria siceraria Stand, Trigonella foenum-graecum. METHODS: Literature
      searches were done using keywords for plants, nutraceuticals, and plant products
      that have revealed beneficial effects in the prevention of CVDs. The anti-oxidant
      and anti-inflammatory actions of nutraceuticeuticals and plant ingredients play a
      significant role in capturing free radicals and reducing endothelial risk factors
      associated with the occurrence CVDs. RESULTS: This review has explored the
      usefulness of animal studies performed with nutraceuticals and herbal products
      and to understand their mode of action in the prevention of CVDs. Also, we have
      referred to patents for different nutraceuticals for better understanding their
      quantitative effects and dosage forms. CONCLUSION: It is concluded that
      nutraceuticals possess enormous health benefits and their interventions can be
      highly beneficial in the prevention/reduction of CVDs and related disorders such
      as atherosclerosis, hypertension, heart attack and stroke. The findings of this
      review provide an update on the emerging uses of nutraceuticals, functional
      foods, and herbal remedies in humans. Nevertheless, large-scale randomized,
      placebo-controlled, double-blind clinical trials are needed to confirm the health
      benefit claims about nutraceuticals and herbal products to establish their long
      term safety and to resolve the controversy about the role of clinical nutrition
      in curing lifestyle diseases.

PMID- 30109828
TI  - Review: Livestock production increasingly influences wildlife across the globe.
AB  - With the growing human population, and their improving wealth, it is predicted
      that there will be significant increases in demand for livestock products (mainly
      meat and milk). Recent years have demonstrated that the growth in livestock
      production has generally had significant impacts on wildlife worldwide; and these
      are, usually, negative. Here I review the interactions between livestock and
      wildlife and assess the mechanisms through which these interactions occur. The
      review is framed within the context of the socio-ecological system whereby people
      are as much a part of the interaction between livestock and wildlife as the
      animal species themselves. I highlight areas of interaction that are mediated
      through effects on the forage supply (vegetation) - neutral, positive and
      negative - however, the review broadly analyses the impacts of livestock
      production activities. The evidence suggests that it is not the interaction
      between the species themselves but the ancillary activities associated with
      livestock production (e.g. land use change, removal of predators, provision of
      water points) that are the major factors affecting the outcome for wildlife. So
      in future, there are two key issues that need to be addressed - first, we need to
      intensify livestock production in areas of 'intensive' livestock production in
      order to reduce the pressure for land use change to meet the demand for meat
      (land sparing). And second, if wildlife is to survive in areas where livestock
      production dominates, it will have to be the people part of the socio-ecological
      system that sees the benefits of having wildlife co-exist with livestock on
      farming lands (land sharing and win-win).

PMID- 30109829
TI  - Illustrating natural history: images, periodicals, and the making of nineteenth
      century scientific communities.
AB  - This paper examines how communities of naturalists in mid-nineteenth-century
      Britain were formed and solidified around the shared practices of public
      meetings, the publication and reading of periodicals, and the making and printing
      of images. By focusing on communities of naturalists and the sites of their
      communication, this article undermines the distinction between amateur and
      professional scientific practice. Building on the notion of imagined communities,
      this paper also shows that in some cases the editors and illustrators utilized
      imagery to construct a specifically British naturalist community. Following three
      'amateur' natural-history periodicals (Science Gossip, Midland Naturalist and the
      Journal of the Quekett Microscopical Club) the article demonstrates how the
      production and reproduction of natural history in the nineteenth century was
      contingent on community debate - and that this debate both was highly visual and
      moved across printed and geographical boundaries. This paper investigates images
      both for their purported success and for their ascribed value to natural history.
      Additionally, it considers the debates over their limitations and alleged
      failures of printing. Altogether, the article argues that investigating the
      communal practices of observation, writing, drawing and engraving allows for a
      better understanding of the shared practices of nineteenth-century natural
      history.

PMID- 30109826
TI  - Physiological Consequences of Coronary Arteriolar Dysfunction and Its Influence
      on Cardiovascular Disease.
AB  - To date, the major focus of diagnostic modalities and interventions to treat
      coronary artery disease has been the large epicardial vessels. Despite
      substantial data showing that microcirculatory dysfunction is a strong predictor
      of future adverse cardiovascular events, very little research has gone into
      developing techniques for in vivo diagnosis and therapeutic interventions to
      improve microcirculatory function. In this review, we will discuss the
      pathophysiology of coronary arteriolar dysfunction, define its prognostic
      implications, evaluate the diagnostic modalities available, and provide
      speculation on current and potential therapeutic opportunities.

PMID- 30109830
TI  - Awareness and documentation of the teratogenic effects of valproate among women
      of child-bearing potential.
AB  - Aims and methodWe aimed to evaluate clinical note documentation of valproate
      prescribing and establish the level of knowledge among women of child-bearing
      potential regarding valproate-associated adverse effects, including
      teratogenesis, in a regional Irish mental health service. RESULTS: Of the 42
      women prescribed sodium valproate, 21.4% (n = 9) had some documentation in
      relation to associated risks and 33.3% (n = 14) described an awareness of these
      risks from consultation with their treating mental health team. On clinical
      interview, 9.5% (n = 4) of individuals with clear documentation of the risks of
      teratogenesis described no such awareness. Augmentation with lithium was
      associated with greater awareness of the teratogenic risks of valproate (P =
      0.011).Clinical implicationsA clear description of the teratogenic risks of
      valproate and potential management strategies, including advice regarding
      contraception and supplementation with folic acid, should be clearly documented
      and provided repeatedly and in context to all women of child-bearing age who are
      prescribed valproate.Declaration of interestNone.

PMID- 30109831
TI  - Review: Individual variability in feeding behaviour of domesticated ruminants.
AB  - Individual animals behave differently from one another, especially when
      confronting challenges such as changes in diet (e.g. weaning), environment (e.g.
      moving from pasture to feedlot) and social grouping (e.g. movement to lactating
      group after parturition). Each of these challenges involves some element of
      novelty, impacting the welfare and productivity of the animal. Indeed, the large
      individual variability in the development and expression of feeding behaviour
      cannot be fully explained by differences in genetics, management practices, body
      size or growth rate. In this review we outline evidence that individual
      variability in feeding behaviour is associated with the personality of the
      individual. We focus on three key personality traits: exploration, fear or
      reactivity and sociability. Individuals differ in how much they explore their
      feeding environment, with more exploratory individuals being less reactive to
      novel situations. Feeding behaviour can be impaired in individuals that are
      especially reactive to a change in their environment, change in diet or handling
      or restraint by humans. The social environment is also a major factor affecting
      how individuals express their behaviour. Sociability of the individual, including
      dominant-subordinate and affiliative relationships, affects how individuals make
      foraging decisions, gain access to feed and adopt particular social strategies to
      maintain or adjust feeding patterns when the social environment changes.
      Personality traits such as exploration, boldness and sociability also affect the
      use of social information when learning where, how or what to eat. Our review
      highlights the implications of feeding behaviour variability for the welfare and
      productivity of the individual, and how an understanding of personality can help
      tailor management to the needs of the individual.

PMID- 30109832
TI  - Large outbreak of multiple gastrointestinal pathogens associated with fresh curry
      leaves in North East England, 2013.
AB  - A total of 592 people reported gastrointestinal illness following attendance at
      Street Spice, a food festival held in Newcastle-upon-Tyne, North East England in
      February/March 2013. Epidemiological, microbiological and environmental
      investigations were undertaken to identify the source and prevent further cases.
      Several epidemiological analyses were conducted; a cohort study; a follow-up
      survey of cases and capture re-capture to estimate the true burden of cases.
      Indistinguishable isolates of Salmonella Agona phage type 40 were identified in
      cases and on fresh curry leaves used in one of the accompaniments served at the
      event. Molecular testing indicated entero-aggregative Escherichia coli and
      Shigella also contributed to the burden of illness. Analytical studies found
      strong associations between illness and eating food from a particular stall and
      with food items including coconut chutney which contained fresh curry leaves.
      Further investigation of the food supply chain and food preparation techniques
      identified a lack of clear instruction on the use of fresh uncooked curry leaves
      in finished dishes and uncertainty about their status as a ready-to-eat product.
      We describe the investigation of one of the largest outbreaks of food poisoning
      in England, involving several gastrointestinal pathogens including a strain of
      Salmonella Agona not previously seen in the UK.

PMID- 30109833
TI  - Depressive, anxiety, and distress symptoms among cancer patients who endorse
      appearance problems.
AB  - OBJECTIVE: Body image is a vital and complex issue in cancer patients, but not
      well recognized. In the ambulatory psychiatric-oncology clinic, we assessed what
      portion of cancer patients endorsed appearance problems and if they differed in
      terms of depression, anxiety, or distress scores when compared with those who did
      not endorse appearance problems. METHOD: All adult patients with active cancer
      diagnosis seen in the outpatient psychiatry oncology clinic (June 2014-January
      2016) who provided informed consent were included (N = 1,939) in the cross
      sectional study design. "Appearance problems" were assessed as a categorical,
      binomial variable (yes/no) using the National Comprehensive Cancer Network
      Distress Thermometer checklist. Other assessments included the Patient Health
      Questionnaire-9, Patient Health Questionnaire-2, Generalized Anxiety Disorder-7,
      Distress Thermometer, and Edmonton Symptom Assessment Scale.ResultThe overall
      prevalence rate of individuals who endorsed appearance problems was approximately
      36%; they were more likely to be younger, female, Black or Hispanic, and not in a
      committed relationship (all results for demographic variables were statistically
      significant; all p < .001). Importantly, those patients who endorsed appearance
      problems exhibited higher scores for depression (p < .0001), anxiety (p < .0001),
      and distress (p < .0001), and these differences were of medium effect size
      (Cohen's d = 0.5-0.6).Significance of resultsThe current results underscore the
      need to identify patients with body image problems early given that they are
      likely to exhibit higher magnitude of anxiety, depression and distress symptoms
      while undergoing cancer care. The results highlight the importance of body image
      issues and the need to evaluate them in cancer patients.

PMID- 30109834
TI  - Assessing the severity of influenza: a role for longitudinal telephone surveys?
AB  - During the 2009 influenza pandemic, a rapid assessment of disease severity was a
      challenge as a significant proportion of cases did not seek medical care; care
      seeking behaviour changed and the proportion asymptomatic was unknown. A random
      digit-dialling telephone survey was undertaken during the 2011/12 winter season
      in England and Wales to address the feasibility of answering these questions. A
      proportional quota sampling strategy was employed based on gender, age group,
      geographical location, employment status and level of education. Households were
      recruited pre-season and re-contacted immediately following peak seasonal
      influenza activity. The pre-peak survey was undertaken in October 2011 with 1061
      individuals recruited and the post-peak telephone survey in March 2012. Eight
      hundred and thirty-four of the 1061 (78.6%) participants were successfully re
      contacted. Their demographic characteristics compared well to national census
      data. In total, 8.4% of participants self-reported an influenza-like illness
      (ILI) in the previous 2 weeks, with 3.2% conforming to the World Health
      Organization (WHO) ILI case definition. In total, 29.6% of the cases reported
      consulting their general practitioner. 54.1% of the 1061 participants agreed to
      be re-contacted about providing biological samples. A population-based cohort was
      successfully recruited and followed up. Longitudinal survey methodology provides
      a practical tool to assess disease severity during future pandemics.

PMID- 30109817
TI  - Neuroanatomical Framework of the Metabolic Control of Reproduction.
AB  - A minimum amount of energy is required for basic physiological processes, such as
      protein biosynthesis, thermoregulation, locomotion, cardiovascular function, and
      digestion. However, for reproductive function and survival of the species, extra
      energy stores are necessary. Production of sex hormones and gametes, pubertal
      development, pregnancy, lactation, and parental care all require energy reserves.
      Thus the physiological systems that control energy homeostasis and reproductive
      function coevolved in mammals to support both individual health and species
      subsistence. In this review, we aim to gather scientific knowledge produced by
      laboratories around the world on the role of the brain in integrating metabolism
      and reproduction. We describe essential neuronal networks, highlighting key nodes
      and potential downstream targets. Novel animal models and genetic tools have
      produced substantial advances, but critical gaps remain. In times of soaring
      worldwide obesity and metabolic dysfunction, understanding the mechanisms by
      which metabolic stress alters reproductive physiology has become crucial for
      human health.

PMID- 30109835
TI  - Calcium-sensing receptor in nutrient sensing: an insight into the modulation of
      intestinal homoeostasis.
AB  - The animal gut effectively prevents the entry of hazardous substances and
      microbes while permitting the transfer of nutrients, such as water, electrolytes,
      vitamins, proteins, lipids, carbohydrates, minerals and microbial metabolites,
      which are intimately associated with intestinal homoeostasis. The gut maintains
      biological functions through its nutrient-sensing receptors, including the Ca
      sensing receptor (CaSR), which activates a variety of signalling pathways,
      depending on cellular context. CaSR coordinates food digestion and nutrient
      absorption, promotes cell proliferation and differentiation, regulates energy
      metabolism and immune response, stimulates hormone secretion, mitigates secretory
      diarrhoea and enhances intestinal barrier function. Thus, CaSR is crucial to the
      maintenance of gut homoeostasis and protection of intestinal health. In this
      review, we focused on the emerging roles of CaSR in the modulation of intestinal
      homoeostasis including related underlying mechanisms. By elucidating the
      relationship between CaSR and animal gut homoeostasis, effective and inexpensive
      methods for treating intestinal health imbalance through nutritional manipulation
      can be developed. This article is expected to provide experimental data of the
      effects of CaSR on animal or human health.

PMID- 30109837
TI  - Nutritional quality of meals offered to children (kids' meals) at chain
      restaurants in Japan.
AB  - OBJECTIVE: To evaluate the nutritional quality, particularly the fat and salt
      contents, of meals offered to children (kids' meals) at chain restaurants in
      Japan. DESIGN: A web-based content analysis was conducted to evaluate the type of
      restaurant, type of meal, incentives, health claims and nutrition data of kids'
      meals. The nutritional appropriateness of kids' meals was assessed with the
      Standard for the School Lunch Program, which regulates energy (<=2218 kJ),
      protein (20-30 g), fat (<=30 % of energy (E%)) and salt (<2 g) contents of the
      school lunch in Japan. Linear mixed models were employed for evaluating the
      relationship between the characteristics of kids' meals and their fat (E%) or
      salt (g) content. SETTING: Restaurant websites providing nutritional data of
      kids' meals in Japan. SUBJECTS: A total of 438 kids' meals offered by forty-two
      chain restaurant brands from across twenty food-service companies. RESULTS:
      Overall, 58.9, 40.6 and 34.5 % of the kids' meals were determined to be
      appropriate regarding their energy (<=2218 kJ), fat (<=30 E%) and salt content
      (<2 g). In addition, 15.5 % of kids' meals met the multiple standards of energy,
      fat and salt contents. 'Japanese-style' (restaurant-level characteristic) was
      associated with a decrease in the fat E% of kids' meals (beta=-6.2; 95 % CI 
      11.0, -1.4) and an increase in the salt content (beta=0.7; 95 % CI 0.06, 1.3).
      CONCLUSIONS: The characteristics of the restaurant-served kids' meals in Japan
      were high fat E% and high salt content from different cultural contexts of the
      Western and the Japanese diet.

PMID- 30109836
TI  - Staphylococcus lugdunensis sepsis and endocarditis in a newborn following lotus
      birth.
AB  - A term newborn, who underwent lotus birth, developed Staphylococcus lugdunensis
      sepsis and endocarditis on the 1st day of life. This case reports an uncommon
      pathogen known to cause destructive endocarditis in the adult and paediatric
      populations, causing endocarditis in a neonate. We speculate that lotus birth, an
      atypical birthing practice, may have contributed to the development of this
      infection.

PMID- 30109839
TI  - Rapid Triage of Mental Health Risk in Emergency Medical Workers: Findings From
      Typhoon Haiyan - CORRIGENDUM.

PMID- 30109838
TI  - Outcome of Patients With Inherited Neurotransmitter Disorders.
AB  - We report the outcome of 12 patients with inherited neurotransmitter disorders of
      monoamine, tetrahydrobiopterin and gamma amino butyric acid metabolisms from a
      single Inherited Neurotransmitter Disorder Clinic including tyrosine hydroxylase
      (n=2), aromatic l-amino acid decarboxylase (n=1), 6-pyruvoyltetrahydropterin
      synthase, dihydropteridine reductase and succinic semialdehyde dehydrogenase
      deficiencies. Six patients (with 6-pyruvoyltetrahydropterin synthase,
      dihydropteridine reductase and tyrosine hydroxylase deficiencies) had normal
      neurodevelopmental outcome on treatment. Tetrahydrobiopterin loading test in
      newborns with positive newborn screening for phenylketonuria will identify
      patients with 6-pyruvoyltetrahydropterin synthase and dihydropteridine reductase
      deficiencies resulting in abnormal neurotransmitter synthesis in the central
      nervous system in the neonatal period to initiate disease-specific treatment to
      improve neurodevelopmental outcome.

PMID- 30109840
TI  - The fall and rise of Group A Streptococcus diseases.
AB  - Streptococcus pyogenes (or Group A Streptococcus, GAS) is a Gram-positive human
      pathogen responsible for a diverse array of superficial, invasive and immune
      related diseases. GAS infections have historically been diseases of poverty and
      overcrowding, and remain a significant problem in the developing world and in
      disadvantaged populations within developed countries. With improved living
      conditions and access to antibiotics, the rates of GAS diseases in developed
      societies have gradually declined during the 20th century. However, genetic
      changes in circulating GAS strains and/or changes in host susceptibility to
      infection can lead to dramatic increases in the rates of specific diseases. No
      situations exemplify this more than the global upsurge of invasive GAS disease
      that originated in the 1980s and the regional increases in scarlet fever in north
      east Asia and the UK. In each case, increased disease rates have been associated
      with the emergence of new GAS strains with increased disease-causing capability.
      Global surveillance for new GAS strains with increased virulence is important and
      determining why certain populations suddenly become susceptible to circulating
      strains remains a research priority. Here, we overview the changing epidemiology
      of GAS infections and the genetic alterations that accompany the emergence of GAS
      strains with increased capacity to cause disease.

PMID- 30109841
TI  - Whole-exome sequencing reveals doubly novel heterozygous Myosin Binding Protein C
      and Titin mutations in a Chinese patient with severe dilated cardiomyopathy.
AB  - BACKGROUND: Dilated Cardiomyopathy is a serious heart disorder that may induce
      sudden cardiac death and heart failure. Significant progress has been made in
      understanding the molecular basis of dilated cardiomyopathy. In previous studies,
      mutations in more than fifty genes have been identified in dilated cardiomyopathy
      patients. The purpose of this study was to detect the genetic lesion in a family
      from the central south of China affected by severe dilated cardiomyopathy.
      METHODS: Whole-exome sequencing combined with cardiomyopathy-related genes list
      were used to analyse the mutations of the proband. Co-segregation analysis was
      performed by Sanger sequencing.Results and conclusionsTwo novel heterozygous
      mutations - Myosin Binding Protein C: p.L1014RfsX6 and Titin: p.R9793X - were
      identified in the proband. The deletion mutation c.3041delT/p.L1014RfsX6 caused a
      premature stop codon at position 1020 in exon 28 of the Myosin Binding Protein C.
      The nonsense mutation, c.29377 C>T/ p. R9793X, of Titin was located in the highly
      evolutionarily conserved domain, resulting in truncation of the Titin protein as
      well. Co-segregation analysis further revealed that the Myosin Binding Protein C
      mutation came from his mother and the Titin mutation came from his father. Both
      mutations are reported in dilated cardiomyopathy patients for the first time. Our
      study not only provides a unique example of the genes and molecular mechanisms
      involved in dilated cardiomyopathy but also expands the spectrum of Myosin
      Binding Protein C and Titin mutations and contributes to the genetic diagnosis
      and counselling of dilated cardiomyopathy patients.

PMID- 30109842
TI  - Complex lipid globules in early-life nutrition improve long-term metabolic
      phenotype in intra-uterine growth-restricted rats.
AB  - Intra-uterine growth restriction (IUGR) is associated with adverse metabolic
      outcome later in life. Healthy mice challenged with a Western-style diet (WSD)
      accumulated less body fat when previously fed a diet containing large lipid
      globules (complex lipid matrix (CLM)). This study was designed to clarify whether
      an early-life CLM diet mitigates 'programmed' visceral adiposity and associated
      metabolic sequelae after IUGR. In rats, IUGR was induced either by bilateral
      uterine vessel ligation (LIG) or sham operation (i.e. intra-uterine stress) of
      the dam on gestational day 19. Offspring from non-operated (NOP) dams served as
      controls. Male offspring of all groups were either fed CLM or 'normal matrix'
      control diet (CTRL) from postnatal days (PND) 15 to 42. Thereafter, animals were
      challenged with a mild WSD until dissection (PND 98). Fat mass (micro computer
      tomograph scan; weight of fat compartments), circulating metabolic markers and
      expression of 'metabolic' genes (quantitative real-time PCR) were assessed. CLM
      diet significantly reduced visceral fat mass in LIG at PND 40. At dissection,
      visceral fat mass, fasted blood glucose, TAG and leptin concentrations were
      significantly increased in LIG-CTRL v. NOP-CTRL, and significantly decreased in
      LIG-CLM v. LIG-CTRL. Gene expression levels of leptin (mesenteric fat) and
      insulin-like growth factor 1 (liver) were significantly reduced in LIG-CLM v. LIG
      CTRL. In conclusion, early-life CLM diet mitigated the adverse metabolic
      phenotype after utero-placental insufficiency. The supramolecular structure of
      dietary lipids may be a novel aspect of nutrient quality that has to be
      considered in the context of primary prevention of obesity and metabolic disease
      in at-risk populations.

PMID- 30109844
TI  - The influence of a community-level breast-feeding promotion intervention
      programme on breast-feeding practices in Myanmar.
AB  - OBJECTIVE: Breast-feeding in the first 6 months of life is critical for ensuring
      both child health and well-being. Despite efforts to improve breast-feeding
      practices, recent studies have reported that Myanmar continues to have low rates
      of exclusive breast-feeding.Design/Setting/SubjectsA community-based breast
      feeding promotion programme using trained community members was implemented for 1
      year in hard-to-reach townships of Myanmar. The present study assessed the breast
      feeding practices using a cross-sectional survey of 610 mothers of children under
      2 years old: specifically, breast-feeding within 24 h, exclusive breast-feeding
      up to 6 months and breast-feeding duration. RESULTS: Using Cox models for breast
      feeding duration before 24 months, the hazard of breast-feeding cessation was
      lower in programme v. non-programme townships (hazard ratio (HR)=0.55; 95 % CI
      0.32, 0.95). Mothers who worked as shop owners or ran a family business had lower
      hazard of breast-feeding cessation (HR=0.13, P<0.05) v. those who worked as
      supervisors, managers, self-employed and businesswomen. The hazard of breast
      feeding cessation was higher in women in higher wealth quintiles v. those in the
      lowest quintile (lower quintile, HR=3.49, P<0.1; higher quintile, HR=3.50, P<0.1;
      highest quintile, HR=3.47, P<0.1). CONCLUSIONS: The intervention did not affect
      exclusive breast-feeding practices or breast-feeding within the first 24 h.
      Potential reasons include existing high levels of early initiation of breast
      feeding due to ongoing government-led maternal and child health activities, and
      social and traditional practices related to complementary feeding. Community
      based breast-feeding programmes should continue to promote exclusive breast
      feeding and develop strategies to support working mothers.

PMID- 30109843
TI  - Hypophosphataemia in infants with CHD treated with amino acid infant formula.
AB  - OBJECTIVE: Growth among infants with CHD is poor, and is multifactorial with
      multiple contributing factors. Unexplained hypophosphataemia has been reported
      among infants and children with complex medical needs consuming amino acid infant
      formula as the sole source of nutrition. The aim of this audit was therefore to
      review the incidence of hypophosphataemia among infants with CHD. METHODS: The
      use of an electronic patient record search for "amino acid infant formula",
      "CHD", and "cardiac" yielded 136 infants 1 year of age (n=11) and infants with a
      structurally normal heart (n=31) were excluded from the study. The remaining 66
      infants with CHD were given amino acid infant formula.Measurements and main
      resultsIn all, 1059 serum phosphate measures were available. After the
      introduction of amino acid infant formula, significantly more infants with CHD
      had episodes of hypophosphataemia: 15% (n=10/66) before treatment versus 29%
      (n=19/66) after treatment (p=0.049). Mean serum phosphate levels were
      significantly lower in infants with CHD following consumption of amino acid
      infant formula (2.0+/-0.5 versus 1.5+/-0.5 mmol/L following treatment
      (p<0.0001)). Infants with CHD and hypophosphataemia, associated with amino acid
      infant formula, use demonstrated significantly lower weight gain compared with
      those with normal phosphate levels (weight-for-age z scores -2.1+/-1.4 versus 
      0.9+/-1.5; p<0.0001). CONCLUSION: After the introduction of an amino acid
      formula, weight gain was significantly lower among those infants with low
      phosphate levels. There was a significantly higher prevalence of
      hypophosphataemia among infants with CHD after the introduction of amino acid
      infant formula. Lower phosphate levels were associated with lower weight-for-age
      z scores. Infants with CHD are susceptible to poor weight gain; it is therefore,
      crucial the nutritional status of infants prescribed amino acid infant formula is
      more closely monitored to ensure adequate growth.

PMID- 30109845
TI  - Long-term safety and tolerability of aripiprazole lauroxil in patients with
      schizophrenia.
AB  - OBJECTIVE: Safety and tolerability of long-term treatment with the long-acting
      antipsychotic aripiprazole lauroxil (AL) were evaluated in patients with
      schizophrenia. METHODS: This was an international, multicenter, phase 3, 52-week
      safety study of 2 fixed doses of AL (441 mg or 882 mg intramuscular every 4
      weeks). Safety endpoints included adverse events (AEs) and extrapyramidal
      symptoms (EPS) including akathisia, injection-site reactions (ISRs), and
      clinically relevant changes in metabolic and endocrine values. RESULTS: Of 478
      patients entering this study, 236 (49%) continued from a previous 12-week, phase
      3 efficacy study of AL, and 242 (51%) were newly enrolled. Overall, 77% and 23%
      of patients received AL 882 mg (N=368) and 441 mg (N=110), respectively. AEs
      occurred in 50.4% of patients; most were mild (28.7%) or moderate (18.2%). The
      most common AEs were insomnia (8.4%) and increased weight (5.0%). Akathisia was
      reported as an AE in 3.8% of the overall population, with higher rates in
      patients initiating AL on study entry than those continuing on AL. EPS-related
      AEs occurred in 9.4% of patients, and AEs related to metabolic parameters were
      reported in 4.6% of patients. Weight gain was minimal (0.8 kg), and no clinically
      relevant changes were observed for metabolic parameters. The overall incidence of
      ISRs was 3.8%; most were associated with the initial injections in patients
      receiving their first injection in this study. CONCLUSION: Long-term treatment
      with AL is generally well tolerated, with a safety profile consistent with that
      of oral aripiprazole. It is a suitable option for patients with schizophrenia.

PMID- 30109846
TI  - An Introduction to the Structure and Function of the Catalytic Core Enzyme of
      Escherichia coli RNA Polymerase.
AB  - RNA polymerase (RNAP) is the essential enzyme responsible for transcribing
      genetic information stored in DNA to RNA. Understanding the structure and
      function of RNAP is important for those who study basic principles in gene
      expression, such as the mechanism of transcription and its regulation, as well as
      translational sciences such as antibiotic development. With over a half-century
      of investigations, there is a wealth of information available on the structure
      and function of Escherichia coli RNAP. This review introduces the structural
      features of E. coli RNAP, organized by subunit, giving information on the
      function, location, and conservation of these features to early stage
      investigators who have just started their research of E. coli RNAP.

PMID- 30109847
TI  - Continuous subcutaneous insulin infusion versus multiple daily injections in
      children and young people at diagnosis of type 1 diabetes: the SCIPI RCT.
AB  - BACKGROUND: The risk of developing long-term complications of type 1 diabetes
      (T1D) is related to glycaemic control and is reduced by the use of intensive
      insulin treatment regimens: multiple daily injections (MDI) (>= 4) and continuous
      subcutaneous insulin infusion (CSII). Despite a lack of evidence that the more
      expensive treatment with CSII is superior to MDI, both treatments are used widely
      within the NHS. OBJECTIVES: (1) To compare glycaemic control during treatment
      with CSII and MDI and (2) to determine safety and cost-effectiveness of the
      treatment, and quality of life (QoL) of the patients. DESIGN: A pragmatic, open
      label randomised controlled trial with an internal pilot and 12-month follow-up
      with 1 : 1 web-based block randomisation stratified by age and centre. SETTING:
      Fifteen diabetes clinics in hospitals in England and Wales. PARTICIPANTS:
      Patients aged 7 months to 15 years. INTERVENTIONS: Continuous subsutaneous
      insulin infusion or MDI initiated within 14 days of diagnosis of T1D. DATA
      SOURCES: Data were collected at baseline and at 3, 6, 9 and 12 months using paper
      forms and were entered centrally. Data from glucometers and CSII were downloaded.
      The Health Utilities Index Mark 2 was completed at each visit and the Pediatric
      Quality of Life Inventory (PedsQL, diabetes module) was completed at 6 and 12
      months. Costs were estimated from hospital patient administration system data.
      OUTCOMES: The primary outcome was glycosylated haemoglobin (HbA1c) concentration
      at 12 months. The secondary outcomes were (1) HbA1c concentrations of < 48
      mmol/mol, (2) severe hypoglycaemia, (3) diabetic ketoacidosis (DKA), (4) T1D- or
      treatment-related adverse events (AEs), (5) change in body mass index and height
      standard deviation score, (6) insulin requirements, (7) QoL and (8) partial
      remission rate. The economic outcome was the incremental cost per quality
      adjusted life-year (QALY) gained. RESULTS: A total of 293 participants, with a
      median age of 9.8 years (minimum 0.7 years, maximum 16 years), were randomised
      (CSII, n = 149; MDI, n = 144) between May 2011 and January 2015. Primary outcome
      data were available for 97% of participants (CSII, n = 143; MDI, n = 142). At 12
      months, age-adjusted least mean squares HbA1c concentrations were comparable
      between groups: CSII, 60.9 mmol/mol [95% confidence interval (CI) 58.5 to 63.3
      mmol/mol]; MDI, 58.5 mmol/mol (95% CI 56.1 to 60.9 mmol/mol); and the difference
      of CSII - MDI, 2.4 mmol/mol (95% CI -0.4 to 5.3 mmol/mol). For HbA1c
      concentrations of < 48 mmol/mol (CSII, 22/143 participants; MDI, 29/142
      participants), the relative risk was 0.75 (95% CI 0.46 to 1.25), and for partial
      remission rates (CSII, 21/86 participants; MDI, 21/64), the relative risk was
      0.74 (95% CI 0.45 to 1.24). The incidences of severe hypoglycaemia (CSII, 6/144;
      MDI, 2/149 participants) and DKA (CSII, 2/144 participants; MDI, 0/149
      participants) were low. In total, 68 AEs (14 serious) were reported during CSII
      treatment and 25 AEs (eight serious) were reported during MDI treatment. Growth
      outcomes did not differ. The reported insulin use was higher with CSII (mean
      difference 0.1 unit/kg/day, 95% CI 0.0 to 0.2 unit/kg/day; p = 0.01). QoL was
      slightly higher for those randomised to CSII. From a NHS perspective, CSII was
      more expensive than MDI mean total cost (L1863, 95% CI L1620 to L2137) with no
      additional QALY gains (-0.006 QALYs, 95% CI -0.031 to 0.018 QALYs). LIMITATIONS:
      Generalisability beyond 12 months is uncertain. CONCLUSIONS: No clinical benefit
      of CSII over MDI was identified. CSII is not a cost-effective treatment in
      patients representative of the study population. FUTURE WORK: Longer-term follow
      up is required to determine if clinical outcomes diverge after 1 year. A
      qualitative exploration of patient and professional experiences of MDI and CSII
      should be considered. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN29255275 and EudraCT 2010-023792-25. FUNDING: This project was funded by
      the National Institute for Health Research (NIHR) Health Technology Assessment
      programme and will be published in full in Health Technology Assessment; Vol. 22,
      No. 42. See the NIHR Journals Library website for further project information.
      The cost of insulin pumps and consumables supplied by F. Hoffman-La Roche AG
      (Basel, Switzerland) for the purpose of the study were subject to a 25% discount
      on standard NHS costs.

PMID- 30109850
TI  - HIV and Malaria Infections and Associated Risk Factors Among Febrile Illness
      Patients in Northwest Ethiopia.
AB  - OBJECTIVE: Malaria and human immunodeficiency virus (HIV)/acquired
      immunodeficiency syndrome (AIDS) are the major medical challenges of priority
      faced by the sub-Saharan African countries in general and Ethiopia in particular.
      Thus, the aim of this study was to determine the prevalence and associated risk
      factors of HIV and malaria infections among febrile illness patients. METHODS: A
      cross-sectional study was conducted from November 1, 2014 to May 30, 2015 at
      Kolla-Diba Health Center, Northwest Ethiopia. After obtaining informed consent,
      blood samples were collected from each febrile patient for the laboratory
      determination of HIV and malaria infections. Sociodemographic data and other
      associated factors for HIV and malaria infections were collected using a
      structured questionnaire. RESULTS: Of the total of 384 febrile illness patients,
      23.7% (91/384) were positive for Plasmodium species. Of these, the most prevalent
      was P. falciparum, 56.0% (51/91), followed by Plasmodium vivax infection, 38.5%
      (35/91). In this study, 13.8% (53/384) of the participants were positive for HIV.
      Furthermore, 3.13% (12/91) of the participants were coinfected with HIV and
      malaria. According to the findings of the present study, genital ulcer patients
      and those who do not use bed net were significantly associated with HIV and
      malaria infections, respectively. CONCLUSION: Malaria and HIV are still common
      challenges independently occurring in the study area. The coexistence of the two
      diseases cannot be underestimated. Hence, health professionals should strengthen
      the provider initiative counseling and testing (PICT) program as a means of
      HIV/AIDS prevention and control strategy. Furthermore, approaching the febrile
      illness patients for both malaria and HIV diagnoses may help in having a joint
      HIV and malaria prevention and control strategy.

PMID- 30109848
TI  - Constraints on neural redundancy.
AB  - Millions of neurons drive the activity of hundreds of muscles, meaning many
      different neural population activity patterns could generate the same movement.
      Studies have suggested that these redundant (i.e. behaviorally equivalent)
      activity patterns may be beneficial for neural computation. However, it is
      unknown what constraints may limit the selection of different redundant activity
      patterns. We leveraged a brain-computer interface, allowing us to define
      precisely which neural activity patterns were redundant. Rhesus monkeys made
      cursor movements by modulating neural activity in primary motor cortex. We
      attempted to predict the observed distribution of redundant neural activity.
      Principles inspired by work on muscular redundancy did not accurately predict
      these distributions. Surprisingly, the distributions of redundant neural activity
      and task-relevant activity were coupled, which enabled accurate predictions of
      the distributions of redundant activity. This suggests limits on the extent to
      which redundancy may be exploited by the brain for computation.

PMID- 30109849
TI  - The Peptidisc, a simple method for stabilizing membrane proteins in detergent
      free solution.
AB  - Membrane proteins are difficult to work with due to their insolubility in aqueous
      solution and quite often their poor stability in detergent micelles. Here, we
      present the peptidisc for their facile capture into water-soluble particles.
      Unlike the nanodisc, which requires scaffold proteins of different lengths and
      precise amounts of matching lipids, reconstitution of detergent solubilized
      proteins in peptidisc only requires a short amphipathic bi-helical peptide (NSPr)
      and no extra lipids. Multiple copies of the peptide wrap around to shield the
      membrane-exposed part of the target protein. We demonstrate the effectiveness of
      this 'one size fits all' method using five different membrane protein assemblies
      (MalFGK2, FhuA, SecYEG, OmpF, BRC) during 'on-column', 'in-gel', and 'on-bead'
      reconstitution embedded within the membrane protein purification protocol. The
      peptidisc method is rapid and cost-effective, and it may emerge as a universal
      tool for high-throughput stabilization of membrane proteins to advance modern
      biological studies.

PMID- 30109851
TI  - [A proposal for the implementation of Early Intervention in Psychosis (EIP)
      services in Greece: If not now, when?]
AB  - The disorders of the psychosis spectrum, with the most severe being
      schizophrenia, are prevalent and have a great impact on the patients' quality of
      life. The purpose of this article is to highlight the need for a novel national
      strategic approach to the management of psychotic disorders in accordance with
      the international principles of early intervention. Even though outpatient
      treatment is considered adequate, there is an urgent need to adopt an early and
      more comprehensive and effective intervention strategy for young patients with
      psychosis and their families whose clinical and personal needs are clearly not
      met by the existing infrastructure of our mental health services. This can be
      accomplished by the legislation and implementation within the national health
      system of EIP services which on the one hand actively engage community
      organizations with the purpose of early identification of cases, reduction of the
      duration of untreated psychosis and on the other, offer assertive community-based
      support and treatment, based on a multi-disciplinary community team model. The
      effectiveness of early intervention in psychosis is supported by evidence
      provided by 9 international RCTs. The results of these programs indicate a
      superior effect in indexes of quality of life, retention in treatment,
      psychopathology, judicious use of medication and return to work/school as well as
      the patient's effective recovery. International experience (Denmark, Norway,
      Australia, UK, USA, Canada and Italy) and the corresponding prevention programs
      emphasize the effectiveness of EIP services and thus the patients' reintegration.
      However, in contrast to Northern European countries, Southern European countries
      have not yet incorporated EIP services in their national health system. From a
      financial perspective, EIP services seem to be cost-effective for the national
      health system, since the economic burden is compensated in the long term through
      their qualitative benefits. In Greece, specialized services for those young
      afflicted for the first time by the most serious of mental disorders are non
      existent and no local information exists for the patient's outcome and social
      integration after a first psychotic-episode nor for the financial burden, placed
      on mental health services. Overall, the implementation of EIP services is
      expected to have long-term benefits for our country's National Health System as
      well as for the patients and their families.

PMID- 30109852
TI  - [Clinical guidelines for the management of schizophrenia (IotaIota): Community
      service-level interventions and the role of Primary Care].
AB  - Schizophrenia is one of the most disabling disorders globally, with a significant
      impact on the professional, social and personal functioning of those affected.
      Mortality rates are estimated to be 2-2.5 times greater than in the general
      population attributable to not only suicide but also physical illnesses, such as
      cardiovascular, metabolic and infectious diseases. Patients with schizophrenia
      have increased needs for health services which vary according to the stage of the
      illness and the way the disorder affects the patient. A significant part of the
      costs of treating patients with schizophrenia is attributed to the health service
      costs, both to address the disorder itself and its wider effects. In 2015 the
      National Clinical Guidelines for the management of schizophrenia were formulated
      by a Working Group that was set up by the Greek Ministry of Health. In this
      article, a summary of the recommendations (as included in the National Clinical
      Guidelines) is presented, describing the role of primary care and community
      mental health services in the management of schizophrenia. The NICE Guideline
      (National Institute of Clinical Excellence, 2010, 2014) for the management of
      Psychosis & Schizophrenia was utilized as the main guide to develop the Greek
      National Guidelines . In addition the American Psychiatric Association (APA)
      Practice Guideline for the Treatment of Patients with Schizophrenia (APA, 2004),
      the Royal Australian and New Zealand College of Psychiatrists clinical practice
      guidelines for the treatment of schizophrenia and related disorders (Royal
      Australian and New Zealand College of Psychiatrists, 2005), as well as other
      relevant sources were also used. The Working Group also took into consideration
      the available Greek bibliography as well as the external evaluations of the Greek
      psychiatric reform programs. Special effort was made to adapt the international
      experience to the current Greek landscape with its constraints resulting from the
      uneven dispersion of mental health services, the lack of coordination between
      services, the incomplete sectorization of mental health services provided as part
      of the National Health System, the still underdeveloped Primary Care Health
      Service, and last but not least the difficult economic situation in Greece. The
      proposals aim to contribute to the efficient implementation of the provision of
      community mental health services for patients suffering from psychotic disorders,
      focusing in particular on: (a) the role of primary health care services and the
      role of family physician in the treatment of schizophrenia; (b) the cooperation
      and coordination between mental health services and primary care services in
      order to ensure continuity of care (c) designing services that deliver evidence
      based interventions,thus ensuring that a larger proportion of the population
      receives interventions with documented effectiveness in the treatment of
      schizophrenia, in the least restrictive environment. A particular emphasis is
      placed on services that are expected to reduce the need for hospitalization, such
      as crisis intervention services, community interventions aimed at maintaining and
      continuing the treatment of difficult patients who tend to be lost to follow up
      from services and early intervention services in psychosis.

PMID- 30109853
TI  - [Psychosomatic disorders in ancient Greek medicine].
AB  - The concept of psychosomatic disorders, as defined by modern medicine, was
      difficult to be perceived by the ancient Greek physicians. Two main reasons
      contributed to this. One was that physicians in Greek antiquity had formed the
      idea that the mental illnesses that were recognized at that time, namely mania,
      melancholy, frenzy, caros, lethargy, apoplexy, but even epilepsy, was the result
      of a disturbance of the essential elements of the body, the balance of them
      contributed to the preservation of health. Thus, depending on the school of
      medical thought of each physician in antiquity, mental and corporal illnesses
      were the result of various disorders such as the dyscrasia of humors for the
      physicians of the Dogmatic school that followed the Hippocratic principles or the
      disorder of the qualitative characteristics of the humor and the pneuma (air), as
      the physicians of the Pneumatic School considered, but also of the stenosis or
      the expansion of the pores as the physicians of the Methodic school thought.
      Although there was the perception that the diseases were the result of various
      combinations of the previous theories, as concluded by the physicians who
      constituted the Eclectic school. The second reason was that ancient physicians
      could not perceive the autonomy of man's psychic world as an element of human
      nature in which emotional distress and irrational mental processing of stimuli
      from the social, cultural and natural environment of the individual would be
      aggravating to the challenge of mental imbalance. Nevertheless, many physicians
      such as physicians who wrote various work of Corpus Hippocraticum, Soranus of
      Ephesus (1st - 2nd c. AD) Galen (1st - 2nd c. AD), Aretaeus of Cappadocia (1st -
      2nd or 4th c. AD) and Caelius Aurelianus (5th c. AD) did not forget to describe
      in their works psychosomatic disorders as they are defined by modern medicine. In
      their works there are the observations about intense sweating, tremor, eating
      disorders, hysteria and even death as a result of an intense and long
      psychological unrest. These corporal symptoms, although were onset due to a
      psychological unequilibrium they could not been listed by the ancient Greek
      physicians in any of the mental diseases as they were defined in antiquity. The
      psychological disturbance which could provoke the above corporal disorders arose
      by various phobias, shame, sorrow, anger, envy, excessive drinks and food,
      excessive sexual desire, passion for gambling and anxiety of everyday life.

PMID- 30109854
TI  - [Prisoners in Greek prisons: Correlation of demographic and psychosocial data
      with committed crimes].
AB  - Previous literature shows an association between several psychosocial factors or
      life events in general and delinquency. Factors such as gender, cannabis and
      drugs use are firmly connected to delinquency. Similarly, interpersonal violent
      behavior appears to be more frequent in people with lower socioeconomic status
      and people with lower education. The association of these factors with the
      violent or non-violent crimes, especially in Greek research literature, is very
      limited. The present study is an attempt to examine in a Greek prison population
      the correlation of demographic and psychosocial factors with violent and non
      violent crime. The prison population sample comprised of 308 males from a total
      of 1300 prisoners, aged between 18 and 77 years old. The survey was conducted
      from January 2012 until August 2013 in Korydallos and Domokos prisons. In our
      prison population sample most of the crimes were non-violent. The prisoners were
      urban dwellers, of young age, were not married and were in short-term
      relationships on average. They had completed their military obligations, were not
      live alone, and have been working in the last six months before being imprisoned,
      in manual labor. They had low-grade education and poor school achievements, had
      been brawling with classmates and had history of antisocial behavior (liked to
      "put fire" and abuse animals). They report good relationships with their parents;
      however, they had experienced violence in parental relationships and some kind of
      violence, mainly by the father and secondarily by the mother. They have not been
      involved in gangs necessarily and have a history from a young age, of alcohol,
      cannabis and drugs use. Cannabis use history was reported by 208 prisoners
      (67.5%) and 133 (63.9%) of them started using at the age of 10-15 years old. A
      total of 179 prisoners (58.5%) reported a history of drug use, about half of them
      (50.3%) reported being addicted to a combination of drugs. For 40.8% (n=73) drug
      use was initiated in the age of 10-15 years old, while the largest percentage
      (46.4%) of prisoners mentioned as starting age 16-20 years old. Although the
      above features underline the great differences between prison population and the
      general population, there are no significant associations of these factors with
      violent or non-violent crime. However, the prisoners with drug use history were
      65% less likely to have been sentenced for violent crime. Also, the prisoners
      exempted from their military duties, were 49% less likely to have committed
      violent crime.

PMID- 30109856
TI  - [The relationship of internet addiction with anxiety and depressive
      symptomatology].
AB  - Internet stimulates the user's senses causing a variety of subjective experiences
      and sensations, even though it has no inherent addictive quality. These
      experiences could be positive, as the improvement of education, or adverse, as
      the development of internet addiction. There are many people who prefer to invest
      their time and energy in the virtual world of the internet. They choose to
      withdraw their emotional investments from face to face communication, while in
      some cases the internet connection signifies the user's disconnection from the
      real life, as the person is isolated from the surrounding and lives in a virtual
      environment. Under these conditions the excessive use of internet may lead to
      addiction. The purpose of the present study was to investigate the relationship
      between internet addiction and anxiety and depressive symptomatology of the user.
      Participants were 203 internet users aged between 17 and 58 years (Mean=26.03,
      SD=7.92) who approached the Department For Problematic Use Of Internet, Addiction
      Unit "18ANO" in Psychiatric Hospital Of Attica to receive specialized help for
      their pathological internet use. Internet Addiction Test (IAT) was used for the
      assessment of internet addiction and Symptom Checklist- 90-R (SCL-90-R) was
      administered for the evaluation of anxiety and depressive symptomatology. The
      analysis of the survey data showed that gender difference is not observed as to
      the intensity internet dependence. Younger users are more likely to develop
      addictive behaviour (in relation to internet use). At this point it should be
      noted that although positive, this association does not present to be
      statistically significant. Finally, regarding the relationship between
      psychopathology and internet addiction, anxiety symptomatology, which was
      moderately correlated with the overall score at IAT, was found to predict in
      regression analysis the internet addiction. There was no statistically
      significant association between internet addiction and depressive symptomatology,
      with women however, who presented with depressive symptoms to appear more
      vulnerable than men (who requested therapy from the department). Exploration of
      the effects of sex and age on internet addiction is expected contribute to the
      design of the appropriate preventive and therapeutic programs, whereas the study
      of the relationship between internet addiction and other psychiatric disorders
      would contribute the understanding of the mechanisms underpinning the development
      and onset of the addiction.

PMID- 30109855
TI  - [Betaullying and the mental health of schoolchildren with special educational
      needs in primary education].
AB  - The purpose of this study was to investigate the relationship between bullying
      and mental Health in schoolchildren with special educational needs (SEN). Random
      sampling was used to select two groups of children aged 11-12 years, attending
      the fifth and sixth grades of primary school and integration classes in urban and
      rural locations in Greece. The final sample comprised a group of 80 children with
      SEN and a control group of 81 children. The participants completed The Revised
      Olweus Bullying Victim Questionnaire and The Strengths and Difficulties
      Questionnaire (SDQ). The children in the SEN group scored significantly higher on
      both the "Victimization" dimension and the "Intimidation" dimension of the Olweus
      questionnaire than the children in the control group. On the SDQ, the SEN group
      scored significantly higher overall, and in the dimensions "Emotional Symptoms",
      "Hyperactivity" and "Peer Problems", and significantly lower in the dimension
      "Promicron- social Behavior", indicating more mental health problems in
      comparison to the children in the control group. In addition, significant
      correlation was demonstrated between the dimensions "Victimization" and
      "Intimidation" of the Olweus questionnaire and almost all the SDQ dimensions.
      Multifactorial linear regression analysis showed that the SDQ scores were
      independently associated with the Olweus dimensions "Victimization" and
      "Bullying". In addition, higher scores in emotional symptoms and conduct problems
      were associated with higher scores in the dimensions 'Victimization' and
      Intimidation'. Higher scores in "Victimization" were recorded by children with
      SEN, but also by those who had not been born in Greece. Children with SEN and
      those with conduct problems scored higher in the dimension "Bullying" than
      children whose native language was not Greek. In conclusion, this study showed
      that in the fifth and sixth grades of primary school, a group of schoolchildren
      with SEN reported higher levels than a control group of victimization and
      bullying. These findings suggest that there is a great need for raising the
      awareness of this situation among the school staff through the provision of
      special training. Mental health preventive and promotive programs can enable
      school staff to identify students who are at higher risk of becoming victims of
      bullying and victimization. It is also recommended that children with SEN should
      be taught coping strategies against school bullying in the classroom and the
      wider school community.

PMID- 30109857
TI  - [The role of the family in adolescents' subjective well-being].
AB  - The goal of this research is to study the relation between adolescents'
      subjective well-being with: (a) their perceptions regarding their relationship
      with their parents, (b) the corresponding perceptions of their parents and (c)
      parents' subjective well-being. The participants of this study were 714
      adolescents attending the two last grades of Junior High School (Gymnasium) and
      the two last grades of High School (Lyceum) as well as their parents from schools
      of the broader area of Athens randomly selected. The following questionnaires
      were used for data collection from the adolescents who participated in the study:
      (a) The assessment of subjective well-being was based on the Berne Questionnaire
      of Subjective Well-Being/ Youth Form that provides the following factors:
      Positive attitude towards life, Self-esteem, Satisfaction from life, Problems,
      Somatic complaints and Depressive mood. The first three factors are included in a
      general factor called Satisfaction which is the positive aspect of subjective
      well-being (according to the suggested structure of the concept in the relevant
      literature) while the remaining three are included in a second general factor
      called Ill-being which is the negative aspect of subjective well-being, and (b)
      the assessment of family relationships was based on the "Affectual solidarity in
      the family scale" (which was also administered to parents). In addition, parents
      completed the questionnaires "Satisfaction from Life scale" and the "Assessment
      of the emotional satisfaction from life-Keyes scale" for assessing their level of
      subjective well-being. Finally, information on demographics was also collected.
      Statistical analysis of the data included descriptive and deductive methods in
      order to examine the relationship and the interaction of the variables under
      research. Findings revealed several interesting relationships. In particular the
      results showed that the better the relationships are perceived by the adolescents
      the more satisfied they feel from their lives. In particular, the good
      relationships with the mother strengthen the positive dimension of subjective
      well-being while the good relationships with the father decrease the negative
      dimension of subjective well-being. Findings also suggest no significant relation
      among parents' perceptions and their subjective well-being with the well-being of
      the adolescents. The results of the research provide the guidelines for further
      research on the role of the family in adolescents' subjective well-being while
      they also allow for a better understanding of the way adolescents' subjective
      well-being is related to various variables in order to further enhance it through
      appropriate interventions.

PMID- 30109858
TI  - Special issue on emergent collective behaviour from groups of cells.

PMID- 30109859
TI  - Pneumatospinning of collagen microfibers from benign solvents.
AB  - INTRODUCTION: Current collagen fiber manufacturing methods for biomedical
      applications, such as electrospinning and extrusion, have had limited success in
      clinical translation, partially due to scalability, cost, and complexity
      challenges. Here we explore an alternative, simplified and scalable collagen
      fiber formation method, termed 'pneumatospinning,' to generate submicron collagen
      fibers from benign solvents. METHODS AND RESULTS: Clinical grade type I
      atelocollagen from calf corium was electrospun or pneumatospun as sheets of
      aligned and isotropic fibrous scaffolds. Following crosslinking with genipin, the
      collagen scaffolds were stable in media for over a month. Pneumatospun collagen
      samples were characterized using Fourier-transform infrared spectroscopy,
      circular dichroism, mechanical testing, and scanning electron microscopy showed
      consistent fiber size and no deleterious chemical changes to the collagen were
      detected. Pneumatospun collagen had significantly higher tensile strength
      relative to electrospun collagen, with both processed from acetic acid. Stem
      cells cultured on pneumatospun collagen showed robust cell attachment and high
      cytocompatibility. Using DMSO as a solvent, collagen was further co-pneumatospun
      with poly(d,l-lactide) to produce a blended microfibrous biomaterial.
      CONCLUSIONS: Collagen microfibers are shown for the first time to be formed using
      pneumatospinning, which can be collected as anisotropic or isotropic fibrous
      grafts. Pneumatospun collagen can be made with higher output, lower cost and less
      complexity relative to electrospinning. As a robust and rapid method of collagen
      microfiber synthesis, this manufacturing method has many applications in medical
      device manufacturing, including those benefiting from anisotropic
      microstructures, such as ligament, tendon and nerve repair, or for applying
      microfibrous collagen-based coatings to other materials.

PMID- 30109860
TI  - Walking with perturbations: a guide for biped humans and robots.
AB  - This paper provides an update on the neural control of bipedal walking in
      relation to bioinspired models and robots. It is argued that most current models
      or robots are based on the construct of a symmetrical central pattern generator
      (CPG). However, new evidence suggests that CPG functioning is basically
      asymmetrical with its flexor half linked more tightly to the rhythm generator.
      The stability of bipedal gait, which is an important problem for robots and
      biological systems, is also addressed. While it is not possible to determine how
      biological biped systems guarantee stability, robot solutions can be useful to
      propose new hypotheses for biology. In the second part of this review, the focus
      is on gait perturbations, which is an important topic in robotics in view of the
      frequent falls of robots when faced with perturbations. From the human physiology
      it is known that the initial reaction often consists of a brief interruption
      followed by an adequate response. For instance, the successful recovery from a
      trip is achieved using some basic reactions (termed elevating and lowering
      strategies), that depend on the phase of the step cycle of the trip occurrence.
      Reactions to stepping unexpectedly in a hole depend on comparing expected and
      real feedback. Implementation of these ideas in models and robotics starts to
      emerge, with the most advanced robots being able to learn how to fall safely and
      how to deal with complicated disturbances such as provided by walking on a split
      belt.

PMID- 30109861
TI  - Extended stability range of the non-Fermi liquid phase in UCoAl.
AB  - High pressure was used to investigate the stability of the non-Fermi liquid (NFL)
      state, observed in electrical resistivity of uranium-based band metamagnet UCoAl
      in a pure form (paramagnet) or with Fe substitution (ferromagnetic ground state),
      both in a single-crystal form. By combining the pressure variations of
      magnetization and resitivity in these materials the phase diagram for UCoAl had
      been constructed. The band metamagnet transforms into the ferromagnetic state as
      the critical metamagnetic field is reduced to zero by the lattice expansion
      analogous to the negative pressure. Within the same diagram, the increasing
      hydrostatic pressure drives the critical metamagnetic field upwards while
      reducing the magnetization increment at the transition. The NFL state persists to
      about 4-5 GPa. Although spin fluctuations play an important role in the character
      of UCoAl, they do not exhibit any criticality in the sense of divergence of
      parameters describing the resistivity around the Ferro-NFL phase transition,
      which is of the first order type.

PMID- 30109862
TI  - Pressure-induced enhancement in the superconductivity of ZrTe3.
AB  - We report the superconductivity enhancement of ZrTe3 on compression up to 33 GPa.
      The superconducting transition occurs above 4.1 GPa and the superconducting
      temperature (T C) increases with pressure in further compression, reaching a
      maximum of 7.1 K at ~28 GPa. An anomalous change of superconducting temperature
      is seen in the compression above 21 GPa. No structural phase transition is
      observed in the whole compression up to 36 GPa, but a subtle change in structural
      parameter is seen between 17-19 GPa, which seems relevant to the anomalous
      increase in the superconducting temperature. First-principle calculations reveal
      that the density of states at the Fermi level increases with pressure, which
      explains the enhancement of T C in ZrTe3 under compression.

PMID- 30109863
TI  - The utility of high-sensitivity C-reactive protein levels in patients with
      moderate coronary lesions and gray-zone fractional flow reserve.
AB  - OBJECTIVE: It remains controversial whether patients with fractional flow reserve
      (FFR) values of 0.75-0.80 (gray-zone) should be treated with percutaneous
      coronary intervention (PCI). This study aimed to evaluate the prediction of high
      sensitivity C-reactive protein (hs-CRP) levels to guide treatment selection in
      gray-zone patients. METHODS: This prospective interventional trial was conducted
      between January 2015 and March 2016. A total of 785 patients with stable angina
      and single-vessel stenosis with moderate coronary lesions were admitted to
      hospital in this period. After measurement of hs-CRP levels, coronary
      angiography, and FFR, gray-zone patients (n=308) were included in the study and
      were divided into four groups on the basis of a cutoff hs-CRP level of 3 mg/L and
      then on the basis of whether they underwent PCI or not. Patients in groups I (>=3
      mg/L, n=70) and III (<3 mg/L, n=84) underwent PCI, whereas those in groups II
      (>=3 mg/L, n=70) and IV (<3 mg/L, n=84) were administered only drugs. Major
      adverse clinical events (MACEs) included cardiac death, nonfatal myocardial
      infarction (MI), target vessel revascularization (TVR), and PCI or coronary
      artery bypass grafting (CABG). These parameters were also evaluated during follow
      up. RESULTS: The total Kaplan-Meier curves showed macrodistribution differences
      among the four groups (p<0.05). There was a significantly increased MACE
      incidence in group II compared with group I or IV (p=0.039 or 0.006,
      respectively), and an increased incidence in group I compared with group III
      (p=0.028). However, there were no differences in MACE incidence between groups
      III and IV (p=0.095) despite the fact that these patients received different
      treatments. CONCLUSION: Among FFR gray-zone patients, hs-CRP level was a
      predictor of MACE and risk stratification could guide treatment selection.
      Increased hs-CRP levels (>=3 mg/L) are an indication for urgent PCI whereas
      normal levels (<3 mg/L) are an indication for delayed PCI treatment. Patients
      with identical FFR values could require different treatment.

PMID- 30109865
TI  - Correction: Environment-sensitive turn-on fluorescent probes for p53-MDM2 protein
      protein interaction.
AB  - [This corrects the article DOI: 10.1039/C7MD00287D.].

PMID- 30109866
TI  - Correction: Boron-containing delocalised lipophilic cations for the selective
      targeting of cancer cells.
AB  - [This corrects the article DOI: 10.1039/C6MD00383D.].

PMID- 30109864
TI  - Interaction Between Environmental Risk Factors and Catechol-O-Methyltransferase
      (COMT) and X-Ray Repair Cross-Complementing Protein 1 (XRCC1) Gene Polymorphisms
      in Risk of Lung Cancer Among Non-Smoking Chinese Women: A Case-Control Study.
AB  - BACKGROUND Various studies have highlighted the link between polymorphisms in the
      XRCC1 gene (encoding X-ray repair cross-complementing group 1) with the incidence
      of decreased DNA repair capacity and an increased predisposition to cancer.
      Catechol-O-methyltransferase (COMT) plays a crucial role in estrogen-induced
      cancers. In the present study was analyzed the potential influence of XRCC1 and
      COMT gene polymorphisms as predisposing factors from a lung cancer perspective,
      in addition to conducting an investigation into their interaction with
      environmental risk factors in relation to lung cancer among non-smoking Chinese
      women. MATERIAL AND METHODS The XRCC1 gene T-77C, Arg194Trp, Arg280His,
      Arg399Gln, COMT gene 186C>T, and Val158Met mutations were evaluated in peripheral
      blood collected from 261 non-smoking female patients diagnosed with primary lung
      cancer and 265 female patients with benign lung disease. RESULTS The results
      obtained from this study demonstrated that XRCC1-77TC + CC, XRCC1 399Gln/Gln,
      COMT 186CT + TT, COMT 158Val/Met genotypes, type of occupation, cooking-oil
      fumes, and soot exposures were all independent risk factors involved with the
      occurrence of lung cancer among non-smoking women. Moreover, interactions between
      environmental exposure factors as well as XRCC1 and COMT gene polymorphisms were
      determined to play significant contributory roles regarding susceptibility of non
      smoking females to lung cancer. CONCLUSIONS Taken together, T-77C and Arg399Gln
      polymorphisms of the XRCC1 gene, as well as the 186C>T and Val158Met
      polymorphisms of the COMT gene, increased the risk of lung cancer in non-smoking
      women, with the factors of occupation type, cooking-oil fumes, and soot exposures
      representing key contributing factors.

PMID- 30109867
TI  - Correction: Design, synthesis, crystal structure and fungicidal activity of (E)-5
      (methoxyimino)-3,5-dihydrobenzo[e][1,2]oxazepin-4(1H)-one analogues.
AB  - [This corrects the article DOI: 10.1039/C7MD00025A.].

PMID- 30109868
TI  - Correction: Synthesis, characterization and biological application of 5-quinoline
      1,3,5-trisubstituted pyrazole based platinum(ii) complexes.
AB  - [This corrects the article DOI: 10.1039/C7MD00472A.].

PMID- 30109869
TI  - Correction to 'Intramolecular hydrogen bonds in 1,4-dihydropyridine derivatives'.
AB  - [This corrects the article DOI: 10.1098/rsos.180088.].

PMID- 30109871
TI  - Erratum: Moose at their bioclimatic edge alter their behavior based on weather,
      landscape, and predators.
AB  - [This corrects the article DOI: 10.1093/cz/zox047.][This corrects the article
      DOI: 10.1093/cz/zox047.].

PMID- 30109870
TI  - Correction: Chiral ruthenium polypyridyl complexes as mitochondria-targeted
      apoptosis inducers.
AB  - [This corrects the article DOI: 10.1039/C0MD00060D.].

PMID- 30109873
TI  - Spectroscopy-based characterization of Hb-NO adducts in human red blood cells
      exposed to NO-donor and endothelium-derived NO.
AB  - The work presents the complementary approach to characterize the formation of
      various Hb species inside isolated human RBCs exposed to NO, with a focus on the
      formed Hb-NO adducts. This work presents a complementary approach based on
      Resonance Raman Spectroscopy (RRS) supported by Blood Gas Analysis, Electron
      Paramagnetic Resonance Spectroscopy, UV-Vis Absorption Spectroscopy and Mossbauer
      Spectroscopy to characterize the formation of various Hb species, with a focus on
      the Hb-NO adducts formed inside isolated human RBCs exposed to NO, under the
      experimental conditions of low and high levels of oxygen Hb saturation. In the
      present work, we induced Hb-NO adducts using PAPA-NONOate, a NO-donor with known
      chemistry and kinetics of NO release, and confirmed the formation of Hb-NO
      adducts in RBCs incubated with Human Aortic Endothelial Cells (HAECs) stimulated
      to produce NO. Our results provide a new insight into the formation of Hb-NO
      adducts after the exposure of RBCs with high oxyHb content to exogenous NO with
      special attention to the formation of LSHbIIINO in addition to LSHbIINO and metHb
      (HS/LSHbIIIH2O). We also point out that reliable characterization of Hb-NO
      adducts requires complementary techniques. Among them, RRS, as a label-free and
      non-destructive tool, appears to be an important discrimination technique in the
      studies of Hb-NO adducts inside intact RBCs.

PMID- 30109872
TI  - Moose at their bioclimatic edge alter their behavior based on weather, landscape,
      and predators.
AB  - Populations inhabiting the bioclimatic edges of a species' geographic range face
      an increasing amount of stress from alterations to their environment associated
      with climate change. Moose Alces alces are large-bodied ungulates that are
      sensitive to heat stress and have exhibited population declines and range
      contractions along their southern geographic extent. Using a hidden Markov model
      to analyze movement and accelerometer data, we assigned behaviors (rest, forage,
      or travel) to all locations of global positioning system-collared moose (n = 13,
      moose-years = 19) living near the southern edge of the species' range in and
      around Voyageurs National Park, MN, USA. We assessed how moose behavior changed
      relative to weather, landscape, and the presence of predators. Moose
      significantly reduced travel and increased resting behaviors at ambient
      temperatures as low as 15  degrees C and 24  degrees C during the spring and
      summer, respectively. In general, moose behavior changed seasonally in
      association with distance to lakes and ponds. Moose used wetlands for travel
      throughout the year, rested in conifer forests, and foraged in shrublands. The
      influence of wolves Canis lupus varied among individual moose and season, but the
      largest influence was a reduction in travel during spring when near a wolf home
      range core, primarily by pregnant females. Our analysis goes beyond habitat
      selection to capture how moose alter their activities based on their environment.
      Our findings, along with climate change forecasts, suggest that moose in this
      area will be required to further alter their activity patterns and space use in
      order to find sufficient forage and avoid heat stress.

PMID- 30109874
TI  - Chiral Lewis acid-catalyzed enantioselective cyclopropanation and C-H insertion
      reactions of vinyl ketones with alpha-diazoesters.
AB  - Enantioselective cyclopropanation and C-H insertion reactions of alpha
      substituted vinyl ketones with alpha-diazoesters have been accomplished using a
      N,N'-dioxide-scandium(iii) complex catalyst. Various tetrasubstituted
      cyclopropanes and E-enone derivatives bearing a chiral ester substituent were
      obtained simultaneously with good yields and excellent enantioselectivities.

PMID- 30109875
TI  - An injectable and physical levan-based hydrogel as a dermal filler for soft
      tissue augmentation.
AB  - The use of injectable materials as a biofiller for soft tissue augmentation has
      been increasing worldwide. Levan is a biocompatible and inexpensive
      polysaccharide with great potential in biomaterial applications, but it has not
      been extensively studied. In this study, we evaluated the potential of levan as a
      new material for dermal fillers and prepared an injectable and physical levan
      based hydrogel by combining levan with Pluronic and carboxymethyl cellulose
      (CMC). A sol state was prepared by mixing the polymers in a specific ratio at 4 
      degrees C for 2 days and the hydrogel was formed by increasing the temperature to
      37  degrees C. The elastic modulus of the levan hydrogel was higher than that of
      a hyaluronic acid (HA)-based hydrogel. The SEM images of the levan hydrogel
      showed an interconnected porous structure, similar to the HA hydrogel. Levan
      showed non-cytotoxicity, enhanced cell proliferation, and higher amount of
      collagen synthesis in human dermal fibroblast cells compared to HA. The injected
      levan hydrogel was biocompatible and stable over 2 weeks in vivo, longer than the
      Pluronic F127 hydrogel or HA hydrogel. Also, the levan hydrogel showed a higher
      amount of collagen production than the HA hydrogel in vivo. More importantly, the
      levan hydrogel showed enhanced anti-wrinkle efficacy compared to the HA hydrogel
      in a wrinkle model mouse. Thus, the levan hydrogel with injectability,
      biocompatibility, and an anti-wrinkle effect has high potential as an alternative
      to existing commercial dermal fillers.

PMID- 30109878
TI  - Single gold bipyramids on a silanized substrate as robust plasmonic sensors for
      liquid environments.
AB  - Sensitive, robust and stable sensors are required to bring biosensing techniques
      from the forefront of research to clinical and commercial settings. To this end,
      we report on the development of new robust plasmonic sensors consisting of gold
      nano-bipyramids (BPs) grafted to a glass substrate via silanization, associated
      with a novel setup based on Spatial Modulation Spectroscopy allowing the
      measurement of the optical response of individual nano-objects in a liquid
      environment. We thereby show that changes in the refractive index of the medium
      around individual silanized BPs can be detected by measuring their plasmonic
      shift with sensitivities comparable to values reported elsewhere and in good
      agreement with theoretical calculations. The optical response is furthermore
      shown to be stable and robust allowing for repeated measurements in different
      media and storage over many months. This work opens up new perspectives in the
      field of plasmonic bio-sensing as our setup is readily adaptable to dynamic
      liquid measurements and a wide range of applications such as the detection of
      clinically important analytes or pollutants in water.

PMID- 30109880
TI  - Borophene's tryst with stability: exploring 2D hydrogen boride as an electrode
      for rechargeable batteries.
AB  - Graphene's emergence can be viewed as a positive upheaval in 2D materials
      research. Along the same line, the realization of a related elemental 2D
      material, borophene, is another breakthrough. To circumvent the stability issues
      of borophene, which is reported to have been synthesized on metallic substrates
      under extreme conditions, hydrogenation of borophene (otherwise called as
      borophane or hydrogen boride or boron hydride) has been a plausible solution, but
      only proposed computationally. A recent report (H. Nishino, T. Fujita, N. T.
      Cuong, S. Tominaka, M. Miyauchi, S. Iimura, A. Hirata, N. Umezawa, S. Okada, E.
      Nishibori, A. Fujino, T. Fujimori, S. Ito, J. Nakamura, H. Hosono and T. Kondo,
      J. Am. Chem. Soc., 2017, 139(39), 13761-13769) brings to fore its experimental
      realization. Our current study delves into the possibilities of employing this
      intriguing 2D hydrogen boride as anodes in Li/Na ion batteries. Using first
      principles density functional theory methods, we computed relevant properties
      such as the ion (Li/Na) adsorption behavior, the possible pathways of ionic
      diffusion with the estimation of barriers as well as the theoretical specific
      capacities and average voltages to uniquely demonstrate that this material is of
      particular significance for battery applications. It is noted that the use of
      hydrogen boride leads to a high specific capacity of 861.78 mA h g-1 for Li ions,
      which is remarkably higher than the value reported in relation to its
      computationally predicted structure. Furthermore, Na ion intercalation leads to
      negative voltage profiles, implying the unsuitability of 2D hydrogen boride for
      this particular ion. Our findings are timely and pertinent towards adding
      insightful details relevant to the progress of applications of 2D materials for
      energy storage.

PMID- 30109884
TI  - Tailored topography: a novel fabrication technique using an elasticity gradient.
AB  - A facile methodology to create a wrinkled surface with a tailored topography is
      presented herein. The dependency of the elasticity of poly(dimethyl)siloxane
      (PDMS) on the curing temperature has been exploited to obtain a substrate with an
      elasticity gradient. The temperature gradient across the length of PDMS is
      created by a novel set-up consisting of a metal and insulator connected to a
      heater and the highest usable (no degradation of PDMS) temperature gradient is
      used. The time-dependent temperature distributions along the substrate are
      measured and the underlying physics of the dependence of the PDMS elasticity on
      the curing temperature is addressed. The PDMS substrate with the elasticity
      gradient is first stretched and subsequently oxidized by oxygen plasma. Upon
      relaxation, an ordered wrinkled surface with continuously varying wavelength and
      amplitude along the length of PDMS is obtained. The extent of hydrophobicity
      recovery of this plasma oxidized PDMS with varying elasticity has been studied.
      The change in the wavelength and amplitude of the regular patterns on the
      substrate can be controlled by varying operational parameters like applied pre
      strain, plasma power and the heater temperature. It has been found that the
      spatial distributions of the topography and the hydrophobicity collectively
      decide the resultant wettability of the substrate. Such surfaces with gradients
      in the substructure dimensions demonstrate different wetting characteristics that
      may lead to a wide gamut of applications including droplet movement, cell
      adhesion and proliferation, diffraction grating etc.

PMID- 30109890
TI  - Subungual Bowen disease. Complete remission 14 years post-photodynamic therapy
      (PDT).

PMID- 30109889
TI  - Influence of early adalimumab serum levels on immunogenicity and long-term
      outcome of anti-TNF naive Crohn's disease patients: the usefulness of rapid
      testing.
AB  - BACKGROUND: Proactive testing of adalimumab serum levels is debated. AIM: To
      study the association between adalimumab serum levels at week 4 and the
      development of anti-adalimumab drug antibodies and long-term outcome in anti-TNF
      naive Crohn's disease patients. METHODS: Serum samples from 116 biologically
      naive Crohn's disease patients with active disease were prospectively collected
      at baseline, and weeks 4 and 12. Adalimumab serum levels were measured using the
      RIDA(r) QUICK adalimumab lateral flow assay and anti-adalimumab drug antibodies
      were determined using a drug-resistant assay. Pharmacokinetic data were studied
      in relation to clinical outcome. Patients who stopped adalimumab by week 12 due
      to persisting symptoms were considered primary non-responders, whereas initial
      improvement with increasing symptoms after week 12 was considered loss of
      response. Adalimumab continuation until the end of follow-up was considered
      sustained clinical benefit. RESULTS: Patients with low serum levels at week 4
      (<8.3 MUg/mL) were at significantly higher risk of being anti-adalimumab positive
      by week 12 (46.7% vs 13.0%, P = 0.009). After a median follow-up of 89 weeks,
      dose-escalation and sustained clinical benefit were observed in 37.1% and 48.3%
      of patients. The 21.4% of patients who were anti-adalimumab drug antibody
      positive by week 12, had a significantly higher need of dose escalation (P <
      0.001), and experienced sustained clinical benefit less frequently due to primary
      non-response or secondary loss of response (P = 0.02). CONCLUSIONS: Our findings
      support early monitoring of adalimumab serum levels to guide dose optimisation,
      which may prevent immunogenicity and influence long-term outcome. We validated a
      novel lateral flow assay for quantitative determination of adalimumab levels,
      facilitating physicians to optimise therapy immediately at the outpatient clinic.

PMID- 30109892
TI  - A prospective diagnostic study on povidone-iodine retention in lesions suspected
      to be squamous cell carcinoma or keratoacanthoma.
AB  - BACKGROUND AND OBJECTIVES: While dermatoscopy improves diagnostic accuracy for
      raised nonpigmented lesions, those with white surface keratin can be
      problematical. We investigated whether retention of povidone-iodine by surface
      keratin provides a clue to benignity. METHODS: We performed a retrospective pilot
      study (n = 57) followed by a prospective study (n = 117) on raised nonpigmented
      lesions with white surface keratin. An initial dermatoscopic image was taken of
      each lesion, povidone-iodine was applied and another image taken. Following
      lavage with 70% ethanol, a third image was acquired. The percentage surface area
      of residual povidone-iodine staining after lavage was recorded, and the results
      analysed. RESULTS: The optimal cut-off point of residual staining was 80%, where
      values of <=80% pointed to malignancy. At this cut-off, the OR for lesions with
      values <=80% to be truly malignant in the retrospective set was 4.03 (95% CI: 2.1
      7.6) and the AUC was 0.7 (95% CI: 0.62-0.78). For the prospective set, the
      corresponding OR was 2.3 (95% CI: 1.4-3.7) and the AUC was 0.62 (95% CI: 0.55
      0.68). CONCLUSIONS: This study presents evidence that povidone-iodine retention
      may have a degree of efficacy in distinguishing benign from malignant keratotic
      lesions. Further study is warranted.

PMID- 30109891
TI  - Biochemical efficacy of tioguanine in autoimmune hepatitis: a retrospective
      review of practice in the Netherlands.
AB  - BACKGROUND: Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of
      steroid-sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients
      do not tolerate or respond to these regimens. AIM: To evaluate retrospectively
      the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in
      selected patients with AIH and AIH variant syndromes. METHODS: Records of 52
      patients who received TG therapy were retrieved from nine hospitals in the
      Netherlands. Indications for TG treatment were intolerable side effects on AZA or
      MP (n = 38), insufficient response (n = 11) or first-line treatment (n = 3).
      Treatment efficacy was defined as normalisation of serum aminotransferases and
      serum immunoglobulin G. RESULTS: No serious adverse events occurred in patients
      treated with TG during a median follow-up of 18 months (range 1-194). Treatment
      was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and
      seven (13%) intolerable side effects. Thirty-eight patients were treated with TG
      after intolerable side effects on AZA or MP; 29 patients continued TG therapy of
      whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete
      and one (3%) had no response; nine discontinued treatment. Seven of 11 patients
      with insufficient response to AZA or MP were responsive to TG, three with
      complete and four with incomplete biochemical remission; four discontinued due to
      intolerance (n = 2) and non-response (n = 2). TG was effective in all AIH
      patients as first-line maintenance treatment. CONCLUSION: In our retrospective
      review of TG therapy in selected patients with AIH or AIH variants who previously
      failed on AZA or MP, TG appeared tolerable with biochemical efficacy.

PMID- 30109893
TI  - Complete resolution and periodic recurrence of multiple postradiation atypical
      vascular lesions.

PMID- 30109894
TI  - International variations in trust in health care systems.
AB  - Public trust in health care systems has been measured in many countries, but
      there have been few studies of the intercountry variability in trust, or the
      degree to which such variability is because of population or structural
      characteristics. We used data from the health care survey conducted by the
      International Social Survey Program from 2011 to 2013 in 31 countries to assess
      whether intercountry variability was significantly greater than intracountry
      variability using general linear models in which country was treated as a fixed
      factor. We also assessed the extent to which intercountry variability was because
      of respondent and economic circumstances (gross national income per capita).
      Public trust in the health care system varied significantly across countries (P <
      .001), even after adjustment for 8 within-country predictors and gross national
      income per capita. One of the strongest predictors of trust was the respondents'
      most recent health care experience. Higher respondent education, urban residence,
      and a lower country's gross national income predicted less trust in the health
      care system. After countries with the 10% highest health expenditures per capita
      (United States) and the 10% lowest health care expenditures per capita (China and
      the Philippines) were removed, public trust in the health care system was
      positively associated with the remaining countries' health care expenditures per
      capita (Pearson correlation coefficient, 0.490; P = .008) and gross national
      income per capita (Pearson correlation coefficient, 0.495; P = .007). There is
      significant variation in public trust in health care across the countries
      studied. The intercountry differences are due, in part to economic circumstances.

PMID- 30109895
TI  - Knowledge and behaviours related to oral health among underserved older adults.
AB  - OBJECTIVE: To examine the mouth and body knowledge, beliefs and behaviours of
      Dominican, Puerto Rican and African American older adults, and their
      relationships to oral and general health and health care. BACKGROUND: In his
      seminal framework, Handwerker posited that the norms, attitudes and behaviours
      related to the experience of disease and treatment reflect where patients live
      and have lived and are seeking and have sought care, along with their webs of
      social and health relations. This framework guides the analysis for the present
      study, wherein qualitative data are used to understand mouth and body knowledge,
      beliefs and behaviours among racial/ethnic minority older adults, ie, why
      individuals do what they do and what it means to them. MATERIALS AND METHODS:
      Focus groups were conducted in Spanish or English with 194 racial/ethnic minority
      older adults living in northern Manhattan who participated in one of 24 focus
      group sessions about improving oral health. All groups were digitally audio
      recorded, transcribed and translated into English from Spanish, where apt.
      Analysis involved the classification of evidence from all datasets, organised to
      identify patterns and relationships. RESULTS: Four themes were manifest in the
      data regarding cultural understandings of the mouth, the body and health: (a) the
      ageing mouth and its components; (b) the mouth in relation to the body, health
      and disease; (c) social meanings of the mouth; and (d) care of the ageing mouth.
      CONCLUSION: Underserved older adults from diverse cultural backgrounds understand
      the importance of their mouths to both their overall health and social lives.

PMID- 30109896
TI  - Asymmetric Reactions involving Lewis Base Catalyst Tethered Dearomatized
      Intermediates.
AB  - Numerous protocols have been developed for the functionalization of aromatic
      substances. Among them, the strategy by which aromatic substrates are activated
      in situ to generate dearomatized intermediates is highly efficient but
      challenging, especially in the field of asymmetric catalysis. In this Concept
      article, the application of some well-established chiral Lewis base catalysis,
      including primary/secondary amines and N-heterocyclic carbenes, that can
      covalently form catalyst-tethered dearomatized ortho/para-quinodimethane species
      with diverse heteroaryl and aryl carbonyl substrates is summarized in a number of
      asymmetric cycloaddition and addition reactions with diverse reagents generally
      having electrophilic properties. As a result, a variety of enantioenriched
      aromatic products with higher molecular complexity are constructed effectively
      through a rearomatization process.

PMID- 30109897
TI  - The effect of the latest health care reforms on the quality of community health
      services in China.
AB  - The Chinese government initiated a new round health care reform in 2009 to
      provide universal primary health care to the country's population. The aim of
      this study was to evaluate and compare the quality of community health services
      before and after the latest health care reforms in China. A series of nationwide
      surveys were conducted in 2008 and in 2011to assess the development of the
      community health services. A total of 2274 and 2501 community health centers, 38
      200 and 42 200 prescriptions, and 12 163 and 12 386 outpatients visited community
      health centers (CHCs) were investigated in 2008 and in 2011, respectively.
      Multivariable regressions and Kruskal-Wallis tests were applied to analyze the
      differences before and after health care reforms. Quality of community health
      services has been improved significantly at the first stage of health care
      reforms in China. CHCs were larger and better equipped after health care reforms
      in terms of average building area and average number of medical equipment.
      Patient satisfaction increased, and patient payments per visit decreased after
      health care reforms. But there was no significant improvement in health human
      resource, and overuse of injections remains prevalent, pointing to the need for
      further reforms to improve quality of community health services, such as general
      practitioner cultivation and supervision over prescribing behaviors.

PMID- 30109898
TI  - Success factors for universal access to antiretroviral treatments in South
      Africa.
AB  - This article studies the epidemiological and economic impacts of a universal
      testing and treatment policy of Human Immunodeficiency Virus (HIV) in South
      Africa. A model of disease transmission is built to simulate several
      implementation scenarios of the policy. Different behavioral responses in the
      general population are considered. The results show that the success of a large
      scale HIV testing and treatment program in South Africa depends on its
      implementation conditions. The policy can lead to a reduction of the HIV
      epidemic, even in the case of a large relapse in preventive behaviors in the
      general population, if implementation conditions are favorable. This is the case
      if the number of infected individuals who are infectious is greatly reduced. From
      an economic point of view, taking into account the positive externality of
      antiretroviral (ARV) treatments changes the traditional framework of cost-benefit
      analyses. A large-scale testing and treatment program would be cost-saving in the
      case of favorable implementation conditions, even following a large increase in
      risk behaviors after the scaling up of ARV treatments. By contrast, the analysis
      stresses out the potential perverse effects of scaling up ARV treatments in South
      Africa if the intervention is set up without ensuring enough resources for
      patients' monitoring and the availability of effective ARV drugs. Indeed, if the
      number of treated patients rises while adherence of patients to treatments
      decreases and the rate of loss to follow-up increases, the policy could extend
      the pool of infectious patients and lead to a long-term amplification of the
      epidemic.

PMID- 30109899
TI  - Pt9 Ni Wavelike Nanowires with High Activity for Oxygen Reduction Reactions.
AB  - Platinum (Pt)-based nanostructures are the most efficient catalysts for the
      oxygen reduction reaction (ORR) in acid media. Here, Pt9 Ni wavelike nanowires (W
      NWs) have been synthesized by etching Pt3 Ni@PtNi2 core-shell nanowires with 2,5
      dihydroxyterephthalic acid for 24 hours. Compared to the commercial Pt/C
      catalyst, the free-standing Pt9 Ni W-NWs show improvements of up to 9.3 times for
      mass activity and 12.6 times for specific activity, respectively.

PMID- 30109900
TI  - The health care reform in Portugal: Outcomes from both the New Public Management
      and the economic crisis.
AB  - The Portuguese health system concentrates most of its activity in a National
      Health Service, created in 1979 to promote universal and general access. The
      National Health Service should ensure equity, efficiency, and quality of all
      health care delivered services. This study assesses the impact of health care
      policies between 2002 and 2017, focusing on 3 timeframes: the adoption and
      adaptation of New Public Management principles to the health care sector (2002 to
      2010), the economic and financial crisis period (2011-2015), and the postcrisis
      recovery period (2016-2017). The current study evaluates the main policy measures
      in the health sector, presenting their impacts in terms of access, efficiency,
      accountability, and costs over those 3 economic periods. It was verified that not
      all the measures implemented by the successive governments obtained the desired
      outcomes, generating even costs increase, apart from the austerity period in
      which health expenditure showed a significant reduction because of the financial
      constraints.

PMID- 30109901
TI  - Costs and efficiency of gatekeeping under varying numbers of general
      practitioners.
AB  - We study the relationship between gatekeeping on one hand and costs as well as
      efficiency on the other hand. We do this with special focus on the relative
      amount of general practitioners in the system when compared with all
      practitioners. Data collected between 2002 and 2011 by The Organization for
      Economic Co-operation and Development on 34 countries were analyzed. Of those, 18
      countries have gatekeeping systems while 16 do not. The association between
      gatekeeping and health care costs was examined with regression analysis.
      Efficiency was assessed with data envelopment analysis. Finally, the efficiency
      assessments were analyzed with regression techniques to examine if gatekeeping
      and/or the ratio of GPs to all practitioners was associated with efficiency.
      Point estimates indicate that total costs tend to be lower in systems where GPs
      act as gatekeepers. However, efficiency is slightly lower where gatekeeping
      exists. Neither of these results is statistically significant at the 95%
      confidence level. There is also indication that the efficiency of a gatekeeping
      system increases with increased amount of GPs. When GPs are over 30% of
      practitioners, gatekeeping countries have more efficient health care systems than
      their counterparts. Consistent with other studies, we estimate income elasticity
      of health care demand to be 1.12, suggesting that those societies consider health
      care to be a luxury good.

PMID- 30109902
TI  - Comparing costs of a senior wellness care redesign in group and independent
      physician practices of an accountable care organization.
AB  - Primary care redesign for older adult patients is currently ongoing in countries
      with aging populations. One of the main challenges of this type of
      transformations is how to estimate implementation costs in different types of
      health care delivery organizations. This study compares start-up and incremental
      expenses of implementing a primary care redesign across 2 organization types:
      integrated group (n = 31) practices and independent practice association (IPA)
      sites (n = 213). Administrators involved with implementing the redesign completed
      a cost capture template to quantifying expenses. The potential impact of
      measurement error, recollection bias, and implementation models across sites and
      geographic regions was examined in sensitivity analyses. Marginal start-up and
      incremental expenses were higher for Group sites ($122-$328) compared to IPA
      sites ($31-$227). Group and IPA sites, however, implemented the redesign with
      different intensities. According to our analyses, if IPA sites implemented the
      redesign with the same intensity as Group sites, marginal costs would have been
      $5 to $13 higher for IPA sites than for Group sites. This study shows how a
      flexible approach to estimate the cost of a wellness care redesign is needed when
      the intensity of the transformation differs across 2 different types of health
      care organizations.

PMID- 30109904
TI  - Exploring pyloric dynamics in stenting using a distensibility technique.
AB  - BACKGROUND: Perforated duodenal ulcers can be treated with a covered stent. Stent
      migration is a severe complication, sometimes requiring surgery. Pyloric
      physiology during stent treatment has not been studied and mechanisms for
      migration are unknown. The aim of this study was to investigate the pyloric
      response to distention, mimicking stent treatment, using the EndoFLIP. METHODS: A
      nonsurvival study in five pigs was carried out, followed by a pilot study in one
      volunteer. Animals were gastroscoped during anaesthesia and the EndoFLIP was
      placed straddling the pylorus. Baseline distensibility readings were performed at
      stepwise balloon distentions to 20, 30, 40, and 50 mL, measuring pyloric cross
      sectional area and pressure. Measurements were repeated after administration of a
      prokinetic drug and after a liquid meal. In the human study, readings were
      performed in conscious sedation at baseline and after stimulation with
      metoclopramide. KEY RESULTS: During baseline readings, the pylorus was shown to
      open more with increasing distention together with higher amplitude motility
      waves. Reaching maximum distention-volume (50 mL), pyloric pressure increased
      significantly (P = 0.016), and motility waves disappeared. After prokinetic
      stimulation, the pressure decreased and the motility waves increased in frequency
      and amplitude. After food stimulation, the pressure stayed low and the motility
      showed increase in amplitude. During both tests, the pylorus showed higher
      pressure and lack of motility waves at maximum probe distention. CONCLUSIONS AND
      INFERENCES: The pylorus seems to act as a sphincter at low distention but when
      further dilated starts acting as a pump. Fully distended the pyloric motility
      disappears and the pressure remains high, suggesting that a stent with high
      radial force might show less migration.

PMID- 30109903
TI  - Enzymatic Amide Tailoring Promotes Retro-Aldol Amino Acid Conversion To Form the
      Antifungal Agent Aspirochlorine.
AB  - Aspirochlorine is an unusual antifungal cyclopeptide produced by Aspergillus
      oryzae, an important mold used for food fermentation. Whereas its structure
      suggested that a non-ribosomal peptide synthetase assembles the cyclopeptide from
      phenylalanine and glycine building blocks, labeling studies indicated that one
      Phe moiety is transformed into Gly after peptide formation. By means of genetic
      engineering, heterologous expression, biotransformations, and in vitro assays, we
      dissected and reconstituted four crucial steps in aspirochlorine biosynthesis,
      which involve two cytochrome P450 monooxygenases, (AclL and AclO), a
      methyltransferase (AclU), and a halogenase (AclH). We found that the installation
      of the N-methoxylation of the peptide bond sets the stage for a retro-aldol
      reaction that leads to the Phe-to-Gly conversion. The substrate scopes of the
      dedicated enzymes as well as bioassays revealed that the peptide editing has
      evolved to optimize the antifungal action of the natural product.

PMID- 30109906
TI  - Chemically induced inflammation and nerve damage affect the distribution of
      vasoactive intestinal polypeptide-like immunoreactive (VIP-LI) nervous structures
      in the descending colon of the domestic pig.
AB  - BACKGROUND: The enteric nervous system (ENS), situated in the wall of the
      gastrointestinal tract, regulates the majority of intestinal activities in
      physiological conditions and during pathological processes. Enteric neurons are
      diversified in terms of active substance expression. One of the most important
      neuropeptides within the ENS is vasoactive intestinal polypeptide (VIP). It seems
      to be one among the important inhibitory peptides in addition to neuropeptide Y
      (NPY), nitric oxide (NO), and adenosine triphosphate (ATP) of the intestinal
      motility and secretion, however, many issues connected with distribution and
      roles of VIP in the large intestine, especially during pathological states, still
      remain unknown. METHODS: Changes in the VIP-like immunoreactivity of the enteric
      nervous structures under experimental pathological states, including chemically
      induced inflammation and nerve damage was examined using the double
      immunofluorescence technique with commercial antibodies. KEY RESULTS: Generally,
      both pathological factors studied caused an increase in the number of VIP-like
      immunoreactive (VIP-LI) neurons and nerve fibers, but the intensity of
      fluctuations depended on both the acting factor and the part of the ENS studied.
      CONCLUSIONS AND INFERENCES: The obtained results suggest that VIP participates in
      pathological processes concerning the digestive tract, and its exact functions
      probably depend on the type of damaging factor acting on the intestine.

PMID- 30109905
TI  - Inactive individuals with chronic neck pain have changes in range of motion and
      functional performance of the shoulder.
AB  - OBJECTIVE: To correlate the range of movement and functional performance of the
      shoulder with pain measures in inactive individuals with and without neck pain.
      In addition, comparisons were made between the groups. METHODS: The sample
      comprised two groups of inactive adults, aged 18-45 years: chronic neck pain (n =
      30) and healthy subjects (n = 30). All participants had no clinical dysfunction
      in the shoulder joint. Aspects related to neck pain were evaluated with the
      Numerical Rating Scale, Neck Disability Index, and the Catastrophic Thoughts
      about Pain Scale. Range of motion and shoulder functionality was evaluated by
      means of goniometry and the Closed Kinetic Chain Upper Extremity Stability
      (CKCUES) test, respectively. RESULTS: Individuals with neck pain presented
      reduction in CKCUES test (absolute score, mean difference [MD] = -1.50, 95%
      confidence interval [CI] [-2.87, -0.12]) and in abduction (MD = -7.36 degrees ,
      95% CI [-13.84, -0.89]) and lateral rotation (MD = -8.61 degrees , CI [-15.94, 
      1.28]) range of motion. Moreover, weak, significant, and negative association (p
      < 0.05, r = -0.262 to -0.384) was observed between the CKCUES test and pain
      intensity at rest and during active cervical movements, as well as
      catastrophizing. A weak, significant, and negative association (p < 0.05, r = 
      0.256 to -0.389) was also observed between the lateral rotation range of motion
      and catastrophizing, as well as pain intensity both at rest and during active
      movements. CONCLUSION: The greater the neck pain intensity and catastrophizing,
      the lower the functional performance and lateral rotation range of motion of the
      shoulder.

PMID- 30109907
TI  - Auto-regulated Protein Assembly on a Supramolecular Scaffold.
AB  - Controlled protein assembly provides a means to regulate function. Supramolecular
      building blocks, including rigid macrocycles, are versatile triggers of protein
      assembly. Now it is shown that sulfonato-calix[8]arene (sclx8 ) mediates the
      formation of cytochrome c tetramers in solution. This tetramer spontaneously
      disassembles at >=2 equivalents of sclx8 , providing a remarkable example of auto
      regulation. Using X-ray crystallography the sclx8 binding sites on cytochrome c
      were characterized. Crystal structures at different protein-ligand ratios reveal
      varying degrees (up to 35 %) of protein surface coverage by the flexible
      calixarene and suggest a mechanism for oligomer disassembly. The solution
      structure of the oligomer was characterized by small-angle X-ray scattering.
      Overall, the data indicate calixarene-controlled protein assembly and disassembly
      without the requirement for a competitive inhibitor, and point to protein
      encapsulation by a flexible macrocycle.

PMID- 30109908
TI  - Effect of a prebiotic galactooligosaccharide mixture (B-GOS(r)) on
      gastrointestinal symptoms in adults selected from a general population who suffer
      with bloating, abdominal pain, or flatulence.
AB  - BACKGROUND: Prebiotics exert beneficial effects upon gastrointestinal (GI)
      environment, but this is not always accompanied with a positive effect on GI
      symptoms. B-GOS(r) is a prebiotic with high selectivity toward bifidobacteria and
      a variety of other beneficial effects in humans. Here, we investigated its effect
      on GI symptoms in adults who suffer with bloating, abdominal pain, and
      flatulence. METHODS: In a double-blind, placebo-controlled, crossover study, 83
      subjects from the general population who presented with GI symptoms during
      screening period and had a predicted probability of functional bowel disorder of
      more than 75% were randomized to receive either a placebo or the B-GOS(r)
      treatment (2.75 g/d). Subjects were screened for the presence of GI symptoms for
      1 week, they consumed the treatments for 2 weeks, and then went through a 2-week
      washout period, before switching to the other treatment for the final 2 weeks. GI
      symptoms, bowel movements, and stool consistency were assessed in daily and
      weekly questionnaires. Quality of life was assessed weekly and depression and
      anxiety at the end of each treatment period. RESULTS: B-GOS(r) resulted in
      significantly (P < 0.001) lower scores for bloating, flatulence, and abdominal
      pain both from baseline and placebo at the end of first week. The effect was
      sustained at the end of second week. It had no effect on the number of bowel
      movements, consistency of stools, quality of life, or mood throughout the study.
      CONCLUSION: Results suggest that B-GOS(r) could possibly be used in the
      management of bloating, flatulence, or abdominal pain and warrant further
      investigation.

PMID- 30109909
TI  - Modern medicine and the one-size-fits-all approach: A clinician's comment to
      Alexandra Parvan's "Mind Electric" article.
AB  - As a clinician, I can easily agree with the author that a person's own reality of
      being healthy is independent of physical evidence or clinical categories and that
      this perspective should be considered to improve clinical care. However, I cannot
      follow the assumptions about the nature and working of modern medicine and
      psychiatry as typically using "black box" and one-size-fits-all treatments in
      daily practice. I outline several working contexts of doctors where this
      criticism does only marginally apply or not at all and wonder whether the author
      might wish, if possible at all from a philosophical viewpoint, to differentiate
      her concepts with regard to these different contexts. In addition, I think that
      ill health in the field of psychiatry might have to be dealt with differently
      than physical ill health.

PMID- 30109910
TI  - Pyrrole-Based Zwitterionic pi-Electronic Systems That Form Self-Assembled Dimers.
AB  - Pyrrole-based zwitterionic pi-electronic systems including a phenylcarboxylate
      (benzoate) anionic site and an N-methyl pyridinium cation unit were synthesized.
      Spectroscopic and theoretical examinations revealed the intermolecular hydrogen
      bonding interactions of the pyrrole NH group and the 3-pyridinium and 3-benzoate
      ortho-CH moieties of zwitterions with a carboxylate anion to form self-assembled
      dimers. The self-assembled dimers were found to exist in equilibrium with the
      corresponding monomers in DMSO, whose dimerization ability was examined by
      concentration-dependent measurements.

PMID- 30109911
TI  - The Next Generation of Anticancer Metallopharmaceuticals: Cancer Stem Cell-Active
      Inorganics.
AB  - Cancer stem cells (CSCs) are heavily linked to fatal incidences of cancer relapse
      and metastasis. Conventional cancer therapies such as surgery, chemotherapy and
      radiation are largely futile against CSCs. Therefore, highly original approaches
      are needed to overcome CSCs and to provide durable, long-term clinical outcomes.
      Many academia- and pharmaceutical-led studies aimed at developing chemical or
      biological anti-CSC agents are ongoing; however, the application of inorganic
      compounds is rare. In this minireview, we discuss how the chemical diversity and
      versatility offered by metals has been harnessed to develop an unprecedented,
      emerging class of metallopharmaceuticals: CSC-active inorganics. A detailed
      account of their mechanism(s) of action is provided, and possible future
      directions for exploration are also put forward.

PMID- 30109912
TI  - Vibrational Coupling between Organic and Inorganic Sublattices of Hybrid
      Perovskites.
AB  - The interplay of electronic and nuclear degrees of freedom in semiconductor
      hybrid organic-inorganic perovskites determines many of their fundamental
      photophysical properties. For instance, charge carriers are dressed with phonons,
      that is, form polarons, and combination modes composed of strongly mixed
      localized vibrations and delocalized phonons can provide pathways for electronic
      energy relaxation and dissipation. Mixing of the different types of nuclear
      motion in vibrational combination modes requires their strong coupling. The
      direct measurement of coupling between the high-frequency N-H stretch modes of
      the organic methylammonium and formamidinium ions and low-frequency Pb-I phonon
      modes of the inorganic sub-lattice in hybrid organic-inorganic perovskites is
      presented. The results reveal direct and substantial coupling between the non
      covalently interacting organic and inorganic sub-lattices.

PMID- 30109913
TI  - Total Synthesis of Asperchalasines A, D, E, and H.
AB  - The first total syntheses of the cytochalasan dimers asperchalasines A, D, E, and
      H have been accomplished. The key steps of the synthesis include a highly
      stereoselective intermolecular Diels-Alder reaction and a Horner-Wadsworth-Emmons
      macrocyclization to establish the key monomer aspochalasin B, and an
      intermolecular Diels-Alder reaction followed by a biomimetic oxidative
      heterodimerization by 5+2 cycloaddition to furnish asperchalasine A. The
      synthetic efforts provide insight into the biosynthetic pathway of cytochalasan
      dimers and enables the further study of their biological properties.

PMID- 30109914
TI  - Dengue hemophagocytic syndrome: A systematic review and meta-analysis on
      epidemiology, clinical signs, outcomes, and risk factors.
AB  - We systematically searched and meta-analyzed the epidemiological characteristics,
      frequency of clinical signs, and outcomes of dengue-associated hemophagocytic
      lymphohistiocytosis. Ten electronic databases were searched systematically plus
      manual search of reference lists to identify relevant articles published until
      May 2017. The highest number of reported cases were from South-East Asia region
      (62 cases), followed by Western Pacific region (20 cases), and America (31
      cases). The term "dengue hemorrhagic fever" predominated in studies that used the
      World Health Organization 1997 definition (59.7%), whereas "severe dengue"
      predominated in studies using the World Health Organization 2009 definition
      (76.8%). Among 122 cases, fever, splenomegaly, hepatomegaly, anemia,
      thrombocytopenia, and serum ferritin >=500 MUg/L were likely to report by
      articles representing by large sample size. The pooled proportion of these
      findings were as follows: fever 97.2%, hepatomegaly 70.2%, splenomegaly 78.4%,
      thrombocytopenia 90.1%, anemia 76.0%, and serum ferritin >=500 MUg/L 97.1%. This
      study highlighted a high case fatality rate (14.6%) and co-infection among dengue
      hemophagocytic lymphohistiocytosis patients. We suggest that long fever duration,
      persistent thrombocytopenia, elevated serum ferritin, and lactate dehydrogenase
      levels could be good diagnostic indicators for dengue-associated hemophagocytic
      syndrome. Bone marrow aspiration could be used as one criterion for diagnosis but
      is not obligatory. Further research is needed to examine the possible risk
      difference for development of hemophagocytic syndrome and to explore potential
      relationships between specific dengue classifications and dengue-associated
      hemophagocytic syndrome.

PMID- 30109915
TI  - Ambient Electrochemical Synthesis of Ammonia from Nitrogen and Water Catalyzed by
      Flower-Like Gold Microstructures.
AB  - Electrochemical nitrogen reduction to ammonia is proposed as a promising
      alternative to the Haber-Bosch process because it can be driven by renewable
      electricity at ambient conditions. Currently, the development of such a process
      is hampered by the lack of efficient electrocatalysts for the nitrogen reduction
      reaction (NRR). Herein, we report a super-rapid approach for the synthesis of
      flower-like Au microstructures (Au flowers) within 5 s. The obtained Au
      structures are assembled by staggered nanoplates as building blocks, which
      provide abundant electrocatalytically active sites for the NRR. The Au flowers
      achieve a high performance (NH3 yield: 25.57 MUg h-1  mgcat. -1 ; faradaic
      efficiency: 6.05 %), 100 % selectivity (no N2 H4 production), and long-term
      durability toward the electrochemical ammonia production. The work is highly
      valuable for the rapid synthesis of active catalysts for the NRR.

PMID- 30109916
TI  - Origin of Nb2 O5 Lewis Acid Catalysis for Activation of Carboxylic Acids in the
      Presence of a Hard Base.
AB  - The Nb2 O5 surface catalyzes the amidation of carboxylic acids with amines
      through Nb5+ Lewis acid activation of the C=O group. In this work, DFT
      calculations were applied to theoretically investigate the C=O bond activation of
      a model carboxylic acid (acetic acid) on theta-Al2 O3 (110), anatase TiO2 (101),
      and T-Nb2 O5 (100) surfaces. The adsorption sites, adsorption energies, reaction
      energy barriers, electronic properties, and vibrational frequency of acetic acid
      were examined in detail. It was found that the bond activation of the carbonyl
      group is most efficient on Nb2 O5 , although the adsorption energy is larger on
      Al2 O3 and TiO2 . The most efficient C=O bond activation on Nb2 O5 results in the
      lowest energy barrier of C-N bond formation during amidation. The Nb2 O5 surface
      also shows larger tolerance to methylamine and water molecules than Al2 O3 and
      TiO2 surfaces. These crucial factors contribute to the highest amidation
      catalytic reactivity on Nb2 O5 . Furthermore, the position of the mean density of
      states of the d-conduction band of the active metal site relative to the Fermi
      energy level correlates well with the efficiency in the C=O bond activation and,
      consequently, the catalytic activity for amidation. These results suggest that,
      unlike a classical understanding of strong acid sites of metal oxide surfaces,
      interaction of a carbonyl HOMO with an unoccupied metal d-orbital, or, in other
      words, covalent-like interaction between a carbonyl group and metal adsorption
      site, is relevant to the present system.

PMID- 30109917
TI  - An evaluation of diagnostic agreement rates between advanced practice
      physiotherapists and paediatric orthopaedic consultants for children with
      musculoskeletal complaints.
AB  - PURPOSE: The purpose of the present study was to establish diagnostic agreement
      rates between orthopaedic consultants and advanced practice physiotherapists
      (APPs) for paediatric orthopaedic patients, examine the appropriateness of
      referrals by APPs to consultants and report on the surgical conversion rate
      (SCR). METHODS: A retrospective review of all patients referred from an APP
      clinic to orthopaedic consultants was conducted for 2013, with a 3-year
      longitudinal follow-up through to the end of 2016. Study participants were two
      APPs and four orthopaedic consultants at a single site. Descriptive statistics
      report the proportion of appropriate onward referrals and SCRs. Raw proportion
      agreement and kappa coefficients were used to evaluate diagnostic agreement
      rates. RESULTS: The mean raw agreement was 82% (95% confidence interval = 73 to
      87), with 12 of the 15 individual codes demonstrating agreement rates >=90%
      (range 57-100). Good to excellent agreement was demonstrated in almost all
      categories based on the kappa coefficient. Eighty-seven per cent of referrals
      from APPs were deemed to be appropriate by the orthopaedic consultants. The SCR
      was 23%. CONCLUSIONS: This was the first study to evaluate diagnostic agreement
      rates between APPs and orthopaedic consultants, the appropriateness of onward
      referral by APPs and the SCR for paediatric musculoskeletal patients referred
      from an APP clinic. Good to excellent diagnostic agreement was observed for
      routine elective paediatric orthopaedic patients, in tandem with agreement levels
      reported in the adult literature. The study demonstrates that APPs are clinically
      effective in the diagnosis and onward referral of paediatric orthopaedic patients
      in a triage setting.

PMID- 30109918
TI  - Regulation of cytoplasmic RNA stability: Lessons from Drosophila.
AB  - The process of RNA degradation is a critical level of regulation contributing to
      the control of gene expression. In the last two decades a number of studies have
      shown the specific and targeted nature of RNA decay and its importance in
      maintaining homeostasis. The key players within the pathways of RNA decay are
      well conserved with their mutation or disruption resulting in distinct phenotypes
      as well as human disease. Model organisms including Drosophila melanogaster have
      played a substantial role in elucidating the mechanisms conferring control over
      RNA stability. A particular advantage of this model organism is that the
      functions of ribonucleases can be assessed in the context of natural cells within
      tissues in addition to individual immortalized cells in culture. Drosophila RNA
      stability research has demonstrated how the cytoplasmic decay machines, such as
      the exosome, Dis3L2 and Xrn1, are responsible for regulating specific processes
      including apoptosis, proliferation, wound healing and fertility. The work
      discussed here has begun to identify specific mRNA transcripts that appear
      sensitive to specific decay pathways representing mechanisms through which the
      ribonucleases control mRNA stability. Drosophila research has also contributed to
      our knowledge of how specific RNAs are targeted to the ribonucleases including AU
      rich elements, miRNA targeting and 3' tailing. Increased understanding of these
      mechanisms is critical to elucidating the control elicited by the cytoplasmic
      ribonucleases which is relevant to human disease. This article is categorized
      under: RNA in Disease and Development > RNA in Development RNA Turnover and
      Surveillance > Regulation of RNA Stability RNA Turnover and Surveillance >
      Turnover/Surveillance Mechanisms.

PMID- 30109919
TI  - Does use of the LUCAS device improve mortality in adult patients with out-of
      hospital cardiac arrest?
AB  - Out-of-hospital cardiac arrest (OHCA) is a common occurrence in the UK, with
      60,000 cases reported annually. To improve outcomes among these patients it is
      necessary to improve links in the cardiac arrest chain of survival.
      Cardiopulmonary resuscitation (CPR) is one of the main elements of this chain
      because it reduces further ischaemic insult in the brain and heart by
      contributing to blood flow. However, even the best manual CPR provides only 20%
      30% of the normal cardiac output. Despite the emphasis on timely CPR at the
      correct rate and depth, delivery of compressions is suboptimal for many patients
      and mechanical devices may improve outcomes. This article critically appraises
      two important papers on the use of mechanical CPR for OHCA. It also suggests
      potential uses for this treatment option and areas for future research.

PMID- 30109920
TI  - Could Probiotics Be Used to Mitigate Neuroinflammation?
AB  - Neuroinflammatory processes promote a constellation of neurochemical and hormonal
      changes resulting in profound effects on motivational states (anhedonia), mood
      (depression and anxiety disorders), and cognitive function (decrements in
      learning and memory). The enhancement of immunoregulatory processes, such as
      increasing anti-inflammatory cytokines in the CNS, is a highly effective strategy
      for curtailing neuroinflammation. Here, we explore recent evidence that probiotic
      treatment approaches might be an effective strategy to induce long-lasting
      immunoregulation in the CNS and thus mitigate the neural and behavioral effects
      of neuroinflammation.

PMID- 30109921
TI  - Nature-Inspired, 3D Origami Solar Steam Generator toward Near Full Utilization of
      Solar Energy.
AB  - Solar steam generation, due to its capability of producing clean water directly
      by solar energy, is emerging as a promising eco-friendly and energy-efficient
      technology to address global challenges of water crisis and energy shortage.
      Although diverse materials and architectures have been explored to improve solar
      energy utilization, high efficiency in solar steam generation could be
      accomplished only with external optical and thermal management. For the first
      time, we report a deployable, three-dimensional (3D) origami-based solar steam
      generator capable of near full utilization of solar energy. This auxetic platform
      is designed based on Miura-ori tessellation and is able to efficiently recover
      radiative and convective heat loss as well as to trap solar energy via its
      periodic concavity pattern. The 3D solar steam generator device with a nanocarbon
      composite of graphene oxide and carbon nanotubes being photothermal component in
      this work shows a very strong dependence between its solar energy efficiency and
      surface areal density. The device yields an extraordinary solar energy efficiency
      close to 100% under 1 sun illumination at a highly folded configuration. The 3D
      origami device can withstand a great number of folding and unfolding cycles and
      shows unimpaired solar steam generation performances. The unique structural
      feature of the 3D origami structure offers a new insight into the future
      development of highly efficient and easily deployable solar steam generator.

PMID- 30109922
TI  - Amino-Substituted Benzamide Derivatives as Promising Antioxidant Agents: A
      Combined Experimental and Computational Study.
AB  - We prepared a range of N-arylbenzamides with a variable number of methoxy and
      hydroxy groups, bearing either amino or amino-protonated moieties, and used DPPH
      and FRAP assays to evaluate their antioxidant capacity. Most of the systems
      exhibit improved antioxidative properties relative to the reference BHT molecule
      in both assays. Combining results from both sets of experiments, the most
      promising antioxidative potential was displayed by the trihydroxy derivative 26,
      which we propose as a lead compound for a further optimization of the benzamide
      scaffold. Computational analysis helped in interpreting the observed trends and
      demonstrated that protonated systems are better antioxidants than their neutral
      counterparts, while underlying the positive influence of the electron-donating
      methoxy group on the antioxidant properties, thus confirming the experiments. It
      also revealed that the introduction of the hydroxy groups shifts the reactivity
      from both amide and amine groups toward this moiety and additionally enhances
      antioxidative features. This is particularly evident in 26H*+, which owes its
      pronounced reactivity to the stabilizing [O*...H-O] hydrogen bonding between the
      created phenoxyl radical and the two neighboring hydroxy groups. We demonstrated
      that its antioxidative activities are more favorable than those for analogous
      trihydroxy derivatives without the N-phenyl group or without the amide moiety,
      which strongly justifies the employed strategy in utilizing bisphenylamides in
      designing potent antioxidants.

PMID- 30109923
TI  - Palladium-Catalyzed ( Z)-Selective Allylation of Nitroalkanes: Access to Highly
      Functionalized Homoallylic Scaffolds.
AB  - Nitroalkanes undergo decarboxylative allylation in the presence of vinyl
      substituted cyclic carbonates, providing a wide variety of functionalized
      homoallylated compounds with exquisite stereocontrol. This Pd-mediated procedure
      features operational simplicity, versatile substrate combinations, and also
      allows for the sequential introduction of different allyl groups in the
      nitroalkane scaffolds with high levels of stereocontrol through the intermediacy
      of a ( Z)-configured palladacyclic intermediate. As far as we know, the developed
      protocol is the first general Pd-mediated methodology toward ( Z)-configured
      homoallylic nitroalkanes with attractive functional group diversity.

PMID- 30109924
TI  - Infrared-Driven Charge-Transfer in Transition Metal-Containing B12X122- (X = H,
      F) Clusters.
AB  - Density functional theory (DFT) calculations and infrared multiple photon
      dissociation (IRMPD) spectroscopy are employed to probe [TM.(B12H12)]- and
      [TM.(B12H12)2]2- clusters [TM = Ag(I), Cu(I), Co(II), Ni(II), Zn(II), Cd(II)]. A
      comparison is made between the charge-transfer properties of the clusters
      containing the hydrogenated dodecaborate dianions, B12H122-, and the fluorinated
      analogues, B12F122-, for clusters containing Cd(II), Co(II), Ni(II), and Zn(II).
      IRMPD of the [TM.(B12H12)]- and [TM.(B12H12)2]2- species yields B12H11- via
      hydride abstraction and B12H12- in all cases. To further explore the IR-induced
      charge-transfer properties of the B12X122- (X = H, F) cages, mixed-cage
      [TM(B12H12)(B12F12)]2- [TM = Co(II), Ni(II), Zn(II), Cd(II)] clusters were
      investigated. IRMPD of the mixed-cage species yielded appreciable amounts of
      B12F12- and B12H12- in most cases, indicating that charge-transfer to the central
      TM cation is a favorable process; formation of B12F12- is the dominant process
      for the Co(II) and Ni(II) mixed-cage complexes. In contrast, the Zn(II) and
      Cd(II) mixed-cage complexes preferentially produced fragments of the form B xH yF
      z-/2-, suggesting that H/F scrambling and/or fusion of the boron cages occurs
      along the IRMPD pathway.

PMID- 30109925
TI  - Important Role of Intermolecular Interaction in Cobalt(II) Single-Ion Magnet from
      Single Slow Relaxation to Double Slow Relaxation.
AB  - Two cobalt complexes with similar structures were synthesized using quinoline-2
      carboxylic acid (HL) as the ligand. Both complexes are six-coordinated in
      antitriangular prism coordination geometries. There are one and four molecule
      units per cell for 1 and 2, respectively, with nearest Co-Co distances of 7.129
      and 5.855 A, respectively, which lead to their intermolecular interactions zj'.
      Both complexes are field-induced single-ion magnets. Complex 1 shows single slow
      relaxation under Hdc = 1.5 kOe attributed to the moment reversal, while complex 2
      shows double slow relaxation resulting from intermolecular dipolar interaction
      and moment reversal, respectively.

PMID- 30109926
TI  - On-Demand Degradation of Metal-Organic Framework Based on Photocleavable
      Dianthracene-Based Ligand.
AB  - We have designed a rigid photocleavable dianthracene-based ligand that reacts
      with ytterbium as coordination metal ion for the creation of a class of
      tridimensional light-degradable metal-organic framework (MOF). We demonstrated
      that we can obtain a high level of control on the disassembly of the MOF formed
      with this ligand which can be triggered either through light irradiation or
      temperature increase. The reversible 4pi-4pi photodimerization is the intrinsic
      chemical mechanism ruling the ligand and MOF cleavage. In the fields of biology
      and medicine, MOFs have sparked a strong interest as highly porous vehicles for
      drug release but have only been explored so far through the passive leakage of
      their payloads. The designed light-degradable MOFs can potentially overcome this
      limitation and serve as prototypes for drug delivery and corresponding
      therapeutic applications.

PMID- 30109927
TI  - Machine Learning in Drug Discovery.

PMID- 30109928
TI  - Reactions of Auranofin and Its Pseudohalide Derivatives with Serum Albumin
      Investigated through ESI-Q-TOF MS.
AB  - The reactions of auranofin and three pseudohalide derivatives with bovine serum
      albumin were explored by ESI-Q-TOF mass spectrometry; a detailed molecular
      description of the resulting adducts is achieved revealing even subtle
      differences in reactivity within this series of gold(I) complexes. Our study
      shows that this kind of investigative approach, formerly applied to the
      interactions of metal-based drugs with small model proteins of MW 10-15 kDa,
      e.g., cytochrome c and lysozyme, may now be extended with success to far larger
      proteins such as serum albumin (MW 66 kDa).

PMID- 30109929
TI  - R-Domain Phosphorylation by Protein Kinase A Stimulates Dissociation of
      Unhydrolyzed ATP from the First Nucleotide-Binding Site of the Cystic Fibrosis
      Transmembrane Conductance Regulator.
AB  - The cystic fibrosis transmembrane conductance regulator (CFTR) is an asymmetric
      ATP-binding cassette transporter in which ATP hydrolysis occurs only at the
      second of the two composite nucleotide-binding sites whereas there are
      noncanonical substitutions of key catalytic residues in the first site.
      Therefore, in widely accepted models of CFTR function, ATP is depicted as
      remaining bound at the first site while it is hydrolyzed at the second site.
      However, the long lifetime of ATP at nucleotide-binding domain 1 (NBD1) had been
      measured under conditions where the channel had not been activated by
      phosphorylation. Here we show that phosphorylation by protein kinase A (PKA),
      obligatory for channel activation, strongly accelerates dissociation of the
      unhydrolyzed ATP from NBD1 of both full-length and NBD2-deleted CFTR. This
      stimulation of nucleotide release results from phosphorylation of the CFTR
      regulatory domain (residues 634-835) (R-domain). Mimicking phosphorylation by
      mutating the eight phosphorylation sites in the R-domain (8SE) has the same
      robust effect on accelerating the dissociation of ATP from NBD1. These findings
      provide new insight into relationships between R-domain phosphorylation and ATP
      binding and hydrolysis, the two main CFTR regulatory pathways.

PMID- 30109930
TI  - Fully-Zwitterionic Polymer-Supported Ionogel Electrolytes Featuring a Hydrophobic
      Ionic Liquid.
AB  - In this report, fully-zwitterionic (ZI) copolymer scaffolds for ionogel
      electrolytes have been synthesized via in situ photopolymerization using various
      molar ratios of 2-methacryloyloxyethyl phosphorylcholine (MPC) and sulfobetaine
      vinylimidazole (SBVI) within the hydrophobic ionic liquid 1-ethyl-3
      methylimidazolium bis(trifluoromethylsulfonyl)imide (EMI TFSI). Depending on the
      chemical composition of the ZI scaffold, ionogel room temperature ionic
      conductivities are found to vary between 2.5 and 6.7 mS cm-1 at a fixed 20 mol %
      total polymer content. Compressive elastic moduli also exhibit a strong
      dependence on the co-monomer ratio, with values between 23 kPa and 11 MPa
      observed because of different degrees of ZI physical cross-linking. These
      results, together with NMR chemical shift analysis, suggest that the
      phosphorylcholine ZI group of MPC interacts more strongly with EMI TFSI, while
      SBVI prefers to self-aggregate and form dipole-dipole cross-links in the ionic
      liquid (IL). Self-diffusivity measurements of the EMI+ cations and TFSI- anions
      in both ionogel and ZI solution samples confirm that slower ion diffusion in MPC
      containing systems is due to attractive zwitterion/IL interactions, and not
      merely reduced mobility in the presence of a polymeric scaffold. This work
      highlights the importance of relative zwitterion/IL and ZI dipole-dipole
      interactions on the properties of a novel class of fully-ZI polymer-supported
      ionogel electrolytes containing a hydrophobic IL suitable for future electrical
      energy storage applications.

PMID- 30109931
TI  - Charged Carbon Nanomaterials: Redox Chemistries of Fullerenes, Carbon Nanotubes,
      and Graphenes.
AB  - Since the discovery of buckminsterfullerene over 30 years ago, sp2-hybridised
      carbon nanomaterials (including fullerenes, carbon nanotubes, and graphene) have
      stimulated new science and technology across a huge range of fields. Despite the
      impressive intrinsic properties, challenges in processing and chemical
      modification continue to hinder applications. Charged carbon nanomaterials
      (CCNs), formed via the reduction or oxidation of these carbon nanomaterials,
      facilitate dissolution, purification, separation, chemical modification, and
      assembly. This approach provides a compelling alternative to traditional damaging
      and restrictive liquid phase exfoliation routes. The broad chemistry of CCNs not
      only provides a versatile and potent means to modify the properties of the parent
      nanomaterial but also raises interesting scientific issues. This review focuses
      on the fundamental structural forms: buckminsterfullerene, single-walled carbon
      nanotubes, and single-layer graphene, describing the generation of their
      respective charged nanocarbon species, their interactions with solvents, chemical
      reactivity, specific (opto)electronic properties, and emerging applications.

PMID- 30109933
TI  - Mechanism of Time-Dependent Adsorption for Dilauroyl Phosphatidylcholine onto a
      Clean Air-Water Interface from a Dispersion of Vesicles.
AB  - This study focused on mechanisms of adsorption for dilauroyl phosphatidylcholine
      (DLPC) from a dispersion of large, unilamellar vesicles (LUVs) onto a clean air
      water interface. The adsorption kinetics were tracked using dynamic surface
      tension measurements for 0.01-10 mM concentrations of DLPC, contained within
      monodisperse LUVs with mean diameters between 100 and 300 nm. Any lipid in excess
      of the solubility limit, determined to be 1.1(+/-0.7) * 10-5 mM (1.1 * 10-8 M),
      was assumed to be in vesicle form. The adsorption rate was found to increase with
      increasing lipid concentration and decreasing vesicle diameter, indicating a
      clear mechanistic role for the vesicles. An induction regime was observed, during
      which lipid adsorption occurred without significantly changing the surface
      tension. Pressure-area isotherm data suggested that the surface concentration at
      the end of this induction period was ~50% of the concentration at saturation,
      with the latter estimated as 4.2(+/-0.7) * 10-6 mol/m2. Convection was also
      introduced into these experiments to probe the importance of bulk transport
      mechanisms to the overall kinetics. Theoretical expressions for possible
      contributing mechanisms and pathways, via molecular and/or vesicle transport,
      were developed and used to predict associated transport time scales for different
      scenarios. These theoretical time scales were compared to experimentally measured
      characteristic times for a variety of DLPC concentrations, vesicle diameters, and
      convection rates. For DLPC concentrations >=0.25 mM, our results were consistent
      with the monolayer formation arising from a molecular transport mechanism that is
      enhanced by vesicle-to-monomer exchange beneath the interface. At lower
      concentrations, experimental rates of adsorption increased with increasing
      convection, and a strong effect of lipid concentration was also observed. For
      DLPC <=0.25 mM, transport controlled by direct interfacial vesicle adsorption
      reasonably captured the observed effect of lipid concentration; however, neither
      monomer nor vesicle pathway mechanisms captured the influence of convection.
      Understanding the adsorption kinetics for such nearly insoluble surfactant
      systems is important in several areas, including food emulsification, foam or
      microbubble formulation, spray drying techniques, and therapeutics.

PMID- 30109932
TI  - Absolute Quantification of RNA Molecules Using Fluorescence Correlation
      Spectroscopy with Certified Reference Materials.
AB  - The accuracy and precision of quantification values of biomolecules, such as
      nucleic acids, are critical for the reliability of biomedical research and
      clinical examinations. To obtain an accurate quantitative value, it is necessary
      to use a measurement standard that has the same sequence and length as the target
      gene. The absence of an appropriate measurement standard leads to uncertain
      results. The development of a wide variety of different kinds of measurement
      standards, which have different sequences and lengths, is time-consuming and
      troublesome. We employed fluorescence correlation spectroscopy (FCS), which can
      be used to count the molecular number (absolute concentration) regardless of the
      molecular size and shape, without a standard curve. The confocal volume (i.e.,
      the volume of excitation laser focus) of the FCS system was calibrated by
      measuring the primary standard of the fluorescent material. Furthermore, we
      investigated how to avoid artifacts originating from systematic aberrations or
      sample conditions. We validated the RNA concentration obtained from our FCS
      measurements using another primary standard RNA solution as a sample. Here, we
      describe an FCS calibration procedure with fluorescein solution standard
      reference material (SRM) 1932 as a primary standard and cross-validation of FCS
      values using RNA solutions certified reference material (CRM) 6204-a. The
      established method was applied to determine the concentrations of RNA samples
      that can be used as a laboratory working standards. The FCS method with a
      characterized SRM and CRM should serve as a universal method for absolute
      quantification of the number of biomolecules.

PMID- 30109934
TI  - Long-Range Modulations of Electric Fields in Proteins.
AB  - Electrostatic interactions are essential for controlling the protein structure
      and function. Whereas so far experimental and theoretical efforts focused on the
      effect of local electrostatics, this work aims at elucidating the long-range
      modulation of electric fields in proteins upon binding to charged surfaces. The
      study is based on cytochrome c (Cytc) variants carrying nitrile reporters for the
      vibrational Stark effect that are incorporated into the protein via genetic
      engineering and chemical modification. The Cytc variants were thoroughly
      characterized with respect to possible structural perturbations due to labeling.
      For the proteins in solution, the relative hydrogen bond occupancy and the
      calculated electric fields, both obtained from molecular dynamics (MD)
      simulations, and the experimental nitrile stretching frequencies were used to
      develop a relationship for separating hydrogen-bonding and non-hydrogen-bonding
      electric field effects. This relationship provides an excellent description for
      the stable Cytc variants in solution. For the proteins bound to Au electrodes
      coated with charged self-assembled monolayers (SAMs), the underlying MD
      simulations can only account for the electric field changes Delta Eads due to the
      formation of the electrostatic SAM-Cytc complexes but not for the additional
      contribution, Delta Eint, representing the consequences of the potential drops
      over the electrode/SAM/protein interfaces. Both Delta Eads and Delta Eint,
      determined at distances between 20 and 30 A with respect to the SAM surface, are
      comparable in magnitude to the non-hydrogen-bonding electric field in the unbound
      protein. This long-range modulation of the internal electric field may be of
      functional relevance for proteins in complexes with partner proteins (Delta Eads)
      and attached to membranes (Delta Eads + Delta Eint).

PMID- 30109935
TI  - Global Analysis of Lysine 2-Hydroxyisobutyrylome upon SAHA Treatment and Its
      Relationship with Acetylation and Crotonylation.
AB  - Lysine 2-hydroxyisobutyrylation is a newly discovered protein acylation and was
      reported to share acyltransferases and deacylases with the widely studied lysine
      acetylation. The well-known acetyltransferase Tip60 and histone deacetylases HDAC
      2 and HDAC 3 were discovered to be "writer" and "eraser" of this new PTM on
      histones. However, the acyltransferases and deacylases for nonhistone proteins
      are still unclear. In this work, lysine 2-hydroxyisobutyrylome on both histones
      and nonhistone proteins upon SAHA treatment were intensively studied and 8765
      lysine 2-hydroxyisobutyrylation sites on 2484 proteins were identified in A549
      cells. This is the largest data set of lysine 2-hydroxyisobutyrylome in mammalian
      cells to date. It was found that lysine 2-hydroxyisobutyrylation participates in
      varieties of biological functions and processes including ribosome,
      glycolysis/gluconeogenesis, and transcription. More importantly, it was found
      that most quantified sites on core histones were up-regulated upon SAHA treatment
      for all 2-hydroxyisobutyrylation, crotonylation, and acetylation and the fold
      changes upon SAHA of 2-hydroxyisobutyrylation and crotonylation on nonhistone
      proteins were highly correlated, while their fold changes have little
      correlations with acetylation on nonhistone proteins.

PMID- 30109936
TI  - Interactions of Silver Nanoparticles Formed in Situ on AFM Tips with Supported
      Lipid Bilayers.
AB  - A facile approach for functionalizing atomic force microscopy (AFM) tips with
      nanoparticles (NPs) will provide exciting opportunities in the field of tip
      enhanced vibrational spectroscopy and in probing the interactions between NPs and
      biological systems. In this study, through successive exposure to polydopamine
      and AgNO3 solutions, the apex of AFM tips was functionalized with silver
      nanoparticles (AgNPs). The AgNP-modified AFM tips were used to measure the
      interaction forces between AgNPs and supported lipid bilayers (SLBs) formed on
      mica, as well as to probe the penetration of SLBs by AgNPs, with an emphasis on
      the effect of human serum albumin (HSA) proteins. AgNPs experienced predominantly
      repulsive forces when approaching SLBs. The presence of HSA resulted in an
      enhancement in the repulsive interactions between AgNPs and SLBs, likely through
      steric repulsion. Finally, the forces required for AgNPs to penetrate SLBs were
      higher in the presence of HSA probably due to the increase in the effective size
      of the nanoscale protuberances on the AFM tip stemming from the formation of
      protein coronas around the AgNPs.

PMID- 30109937
TI  - Examination of the Statistical Effects Associated with Tracking Propulsive
      Particles.
AB  - Particle tracking of active colloidal particles can be used to compute mean
      squared displacements that are fit to extract properties of the particles
      including the propulsive speed. Statistical errors in the mean-squared
      displacement leads to errors in the extracted properties especially for more
      weakly propelling particles. Brownian dynamics simulations in which the particle
      parameters are prescribed were used to examine the statistics of tracking self
      propelling objects. It was found that the manner in which tracking data is
      analyzed has a profound impact on the precision and accuracy of measurements. To
      properly extract particle parameters, it was necessary to apply a nonlinear fit
      of the mean-squared displacement over a time region that includes transition
      behavior from ballistic to diffusive. The dependence of the statistics on the
      number of particles tracked and the length of movies was examined, showing how
      and why weakly propelling particles are difficult to analyze.

PMID- 30109938
TI  - Meloxicam Improves Cognitive Impairment of Diabetic Rats through COX2-PGE2-EPs
      cAMP/pPKA Pathway.
AB  - Diabetics often face greater risk of cognitive impairment than nondiabetics.
      However, how to prevent this disease is still unconfirmed. In this study, we
      investigated the potential protection and mechanism of meloxicam on cognitive
      impairment in diabetic rats. The diabetic rat model was established with a high
      fat diet and a small dose of streptozotocin (40 mg/kg). The changes of spatial
      learning and memory, histopathology, and the protein expressions of amyloid
      protein precursor (APP) and beta-amyloid (Abeta) indicated that diabetic rats had
      neuronal injury and cognitive impairment. Tumor necrosis factor alpha (TNFalpha),
      interleukin 6 (IL-6), C reactive protein (CRP) and prostaglandin E2 (PGE2)
      levels, and microglial cell number were significantly increased in the diabetic
      rat brain. Meanwhile, the protein expressions of APP, Abeta, cyclooxygenases2
      (COX2), E-type prostanoid recptors 1 (EP1) and EP2, and the level of cyclic
      adenosine monophosphate (cAMP) were significantly increased, while the protein
      expressions of EP3 and phosphorylated protein kinase A (pPKA) were significantly
      decreased in the diabetic rat hippocampus and cortex. However, the EP4 protein
      expression had no significant changes. Meloxicam significantly improved neuronal
      injury and cognitive impairment, and significantly decreased inflammatory
      cytokines levels. Meloxicam also significantly decreased the protein expressions
      of APP, Abeta, COX2, EP1 and EP2, and the level of cAMP and significantly
      increased the EP3 and pPKA protein expressions in rat hippocampus and cortex.
      However, meloxicam did not significantly influence the levels of blood glucose,
      lipids, and insulin of rats. Our results suggest that meloxicam could
      significantly protect diabetic rats from cognitive impairment via a mechanism
      that may be associated with rebalancing the COX2-PGE2-EPs-cAMP/PKA pathway.

PMID- 30109939
TI  - Transformation of N, N-Dimethylaniline N-Oxides into Diverse Tetrahydroquinoline
      Scaffolds via Formal Povarov Reactions.
AB  - A one-pot protocol for the assembly of diversely functionalized tetrahydro-,
      hexahydrofuro-, hexahydropyrano-, and tetrahydrobenzofuroquinolines from N, N
      dimethylaniline N-oxides and various electron-rich olefins in a tandem Polonovski
      Povarov sequence is reported. Following activation of the N-O bond with Boc2O, an
      exocyclic iminium ion is unveiled upon exposure to tin(IV) chloride. A formal
      inverse-electron-demand aza-Diels-Alder cyclization generates the
      tetrahydroquinoline core of 29 examples in up to 92% yield.

PMID- 30109940
TI  - Fourth-Generation Antibiotic Gatifloxacin Encapsulated by Microemulsions:
      Structural and Probing Dynamics.
AB  - To overcome the increased disease rate, utilization of the versatile broad
      spectrum antibiotic drugs in controlled drug-delivery systems has been a
      challenging and complex consignment. However, with the development of
      microemulsion (MUE)-based formulations, drugs can be effectively encapsulated and
      transferred to the target source. Herein, two biocompatible oil-in-water (o/w)
      MUE formulations comprising clove oil/Tween 20/ethylene glycol/water (formulation
      A) and clove oil/Tween 20/1-butanol/water (formulation B) were developed for
      encapsulating the gatifloxacin (GTF), a fourth-generation antibiotic. The
      pseudoternary phase diagrams were mapped at a constant surfactant/co-surfactant
      (1:1) ratio to bound the existence of a monophasic isotropic region for as
      formulated MUEs. Multiple complementary characterization techniques, namely,
      conductivity (sigma), viscosity (eta), and optical microscopy analyses, were used
      to study the gradual changes that occurred in the microstructure of the as
      formulated MUEs, indicating the presence of a percolation transformation to a
      bicontinuous permeate flow. GTF showed good solubility, 3.2 wt % at pH 6.2 and
      4.0 wt % at pH 6.8, in optimum MUE of formulation A and formulation B,
      respectively. Each loaded MUE formulation showed long-term stability over 8
      months of storage. Moreover, no observable aggregation of GTF was found, as
      revealed by scanning transmission electron microscopy and peak-to-peak
      correlation of IR analysis, indicating the stability of GTF inside the
      formulation. The average particle size of each MUE, measured by dynamic light
      scattering, increased upon loading GTF, intending the accretion of drug in the
      interfacial layers of microdomains. Likewise, fluorescence probing sense an
      interfacial hydrophobic environment to GTF molecules in any of the examined
      formulations, which may be of significant interest for understanding the kinetics
      of drug release.

PMID- 30109941
TI  - Perspective: SBI2 at Its Fifth Annual Meeting.

PMID- 30109942
TI  - Preliminary Validation of the Montreal Cognitive Assessment Tool among Sepsis
      Survivors: A Prospective Pilot Study.

PMID- 30109943
TI  - Risk Factors for and Prediction of Hypoxemia during Tracheal Intubation of
      Critically Ill Adults.
AB  - RATIONALE: Hypoxemia is a common complication during tracheal intubation of
      critically ill adults and is a frequently used endpoint in airway management
      research. Identifying patients likely to experience low oxygen saturations during
      tracheal intubation may be useful for clinical practice and clinical trials.
      OBJECTIVES: To identify risk factors for lower oxygen saturations and severe
      hypoxemia during tracheal intubation of critically ill adults and develop
      prediction models for lowest oxygen saturation and hypoxemia. METHODS: Using data
      on 433 intubations from two randomized trials, we developed linear and logistic
      regression models to identify preprocedural risk factors for lower arterial
      oxygen saturations and severe hypoxemia between induction and 2 minutes after
      intubation. Penalized regression was used to develop prediction models for lowest
      oxygen saturation after induction and severe hypoxemia. A simplified six-point
      score was derived to predict severe hypoxemia. RESULTS: Among the 433
      intubations, 426 had complete data and were included in the model. The mean
      (standard deviation) lowest oxygen saturation was 88% (14%); median
      (interquartile range) was 93% (83-98%). Independent predictors of severe
      hypoxemia included hypoxemic respiratory failure as the indication for intubation
      (odds ratio [OR], 2.70; 95% confidence interval [CI], 1.58-4.60), lower oxygen
      saturation at induction (OR, 0.92 per 1% increase; 95% CI, 0.89-0.96 per 1%
      increase), younger age (OR, 0.97 per 1-year increase; 95% CI, 0.95-0.99 per 1
      year increase), higher body mass index (OR, 1.03 per 1 kg/m2; 95% CI, 1.00-1.06
      per 1 kg/m2), race (OR, 4.58 for white vs. black; 95% CI, 1.97-10.67; OR, 4.47
      for other vs. black; 95% CI, 1.19-16.84), and operator with fewer than 100 prior
      intubations (OR, 2.83; 95% CI, 1.37-5.85). A six-point score using the identified
      risk factors predicted severe hypoxemia with an area under the receiver operating
      curve of 0.714 (95% CI, 0.653 to 0.778). CONCLUSIONS: Lowest oxygen saturation
      and severe hypoxemia during tracheal intubation in the intensive care unit can be
      accurately predicted using routinely available preprocedure clinical data, with
      saturation at induction and hypoxemic respiratory failure being the strongest
      predictors. A simple bedside score may identify patients at risk for hypoxemia
      during intubation to help target preventative interventions and facilitate
      enrichment in clinical trials.

PMID- 30109945
TI  - The Neutrophilic Response to Pseudomonas Damages the Airway Barrier, Promoting
      Infection by Klebsiella pneumoniae.
AB  - Pseudomonas aeruginosa and Klebsiella pneumoniae are two common gram-negative
      pathogens that are associated with bacterial pneumonia and can often be isolated
      from the same patient. We used a mixed-pathogen pneumonia infection model in
      which mice were infected with sublethal concentrations of P. aeruginosa and K.
      pneumoniae, resulting in significant lethality, outgrowth of both bacteria in the
      lung, and systemic dissemination of K. pneumoniae. Inflammation, induced by P.
      aeruginosa activation of Toll-like receptor 5, results in prolonged neutrophil
      recruitment to the lung and increased levels of neutrophil elastase in the
      airway, resulting in lung damage and epithelial barrier dysfunction. Live P.
      aeruginosa was not required to potentiate K. pneumoniae infection, and flagellin
      alone was sufficient to induce lethality when delivered along with Klebsiella.
      Prophylaxis with an anti-Toll-like receptor 5 antibody or Sivelestat, a
      neutrophil elastase inhibitor, reduced neutrophil influx, inflammation, and
      mortality. Furthermore, pathogen-specific monoclonal antibodies targeting P.
      aeruginosa or K. pneumoniae prevented the outgrowth of both bacteria and reduced
      host inflammation and lethality. These findings suggest that coinfection with P.
      aeruginosa may enable the outgrowth and dissemination of K. pneumoniae, and that
      a pathogen- or host-specific prophylactic approach targeting P. aeruginosa may
      prevent or limit the severity of such infections by reducing neutrophil-induced
      lung damage.

PMID- 30109946
TI  - Quercetin Enhances Ligand-induced Apoptosis in Senescent IPF Fibroblasts and
      Reduces Lung Fibrosis In Vivo.
AB  - While cellular senescence may be a protective mechanism in modulating
      proliferative capacity, fibroblast senescence is now recognized as a key
      pathogenic mechanism in Idiopathic Pulmonary Fibrosis (IPF). In aged mice,
      abundance and persistence of apoptosis-resistant senescent fibroblasts play a
      central role in non-resolving lung fibrosis after bleomycin challenge. Therefore,
      we investigated whether quercetin can restore the susceptibility of senescent IPF
      fibroblasts to pro-apoptotic stimuli and mitigate bleomycin-induced pulmonary
      fibrosis in aged mice. Unlike senescent normal lung (NL) fibroblasts, IPF lung
      fibroblasts from patients with stable and rapidly progressing disease were highly
      resistant to Fas ligand (FasL) and tumor necrosis factor (TNF)-related apoptosis
      inducing ligand (TRAIL)-induced apoptosis. Senescent IPF fibroblasts exhibited
      decreased expression of FasL and TRAIL receptors and caveolin-1, as well as
      increased AKT activation compared with senescent NL fibroblasts. Although,
      quercetin alone was not pro-apoptotic, it abolished the resistance to FasL- or
      TRAIL-induced apoptosis in IPF fibroblasts. Mechanistically, quercetin up
      regulated Fas and caveolin-1 expression, and modulated AKT activation. In vivo,
      quercetin reversed bleomycin-induced pulmonary fibrosis and attenuated lethality,
      weight loss, and the expression of pulmonary senescence markers p21 and p19-ARF
      and senescence-associated secretory phenotype (SASP) in aged mice. Collectively
      these data indicate that quercetin reverses the resistance to death ligand
      induced apoptosis, by promoting FasL receptor and caveolin-1 expression, and
      inhibiting AKT activation, thus mitigating the progression of established
      pulmonary fibrosis in aged mice. Therefore, quercetin may be a viable therapeutic
      option for IPF and other age-related diseases that progress with the accumulation
      of senescent fibroblasts.

PMID- 30109944
TI  - High-Content Screening Campaign to Identify Compounds That Inhibit or Disrupt
      Androgen Receptor-Transcriptional Intermediary Factor 2 Protein-Protein
      Interactions for the Treatment of Prostate Cancer.
AB  - Twenty percent of prostate cancer (PCa) patients develop a noncurable drug
      resistant form of the disease termed castration-resistant prostate cancer (CRPC).
      Overexpression of Androgen Receptor (AR) coactivators such as transcriptional
      intermediary factor 2 (TIF2) is associated with poor CRPC patient outcomes. We
      describe the implementation of the AR-TIF2 protein-protein interaction biosensor
      (PPIB) assay in a high-content screening (HCS) campaign of 143,535 compounds. The
      assay performed robustly and reproducibly and enabled us to identify compounds
      that inhibited dihydrotestosterone (DHT)-induced AR-TIF2 protein-protein
      interaction (PPI) formation or disrupted preexisting AR-TIF2 PPIs. We used
      multiparameter HCS data z-scores to identify and deprioritize cytotoxic or
      autofluorescent outliers and confirmed the resulting qualified actives in
      triplicate. None of the confirmed AR-TIF2 PPIB inhibitors/disruptors exhibited
      activity in a p53-hDM2 PPIB counter screen, indicating that they were unlikely to
      be either nonselective PPI inhibitors or to interfere with the biosensor assay
      format. However, eight confirmed AR-TIF2 PPIB actives also inhibited the
      glucocorticoid receptor (GR) nuclear translocation counter screen by >50%. These
      compounds were deprioritized because they either lacked AR
      specificity/selectivity, or they inhibited a shared component of the AR and GR
      signaling pathways. Twenty-nine confirmed AR-TIF2 PPIB actives also inhibited the
      AR nuclear localization counter screen, suggesting that they might indirectly
      inhibit the AR-TIF2 PPIB assay rather than directly blocking/disrupting PPIs. A
      total of 62.2% of the confirmed actives inhibited the DHT-induced AR-TIF2 PPI
      formation in a concentration-dependent manner with IC50s < 40 MUM, and 59.4% also
      disrupted preexisting AR-TIF2 PPI complexes. Overall, the hit rate for the AR
      TIF2 PPIB HCS campaign was 0.12%, and most hits inhibited AR-TIF2 PPI formation
      and disrupted preexisting AR-TIF2 complexes with similar AR-red fluorescent
      protein distribution phenotypes. Further secondary and tertiary hit
      characterization assays are underway to select AR-TIF2 PPI inhibitor/disruptor
      hits suitable for medicinal chemistry lead optimization and development into
      novel PCa/CRPC therapeutics.

PMID- 30109949
TI  - Lymphangioleiomyomatosis (LAM).

PMID- 30109947
TI  - Countermovement Jump and Isokinetic Dynamometry as Measures of Rehabilitation
      Status After Anterior Cruciate Ligament Reconstruction.
AB  - CONTEXT:   Despite an increase in the literature, few definitive guidelines are
      available to determine when an athlete has been fully rehabilitated after
      anterior cruciate ligament reconstruction (ACLR). OBJECTIVE:   To examine
      countermovement jump and isokinetic dynamometry measures to (1) identify which
      measures can best distinguish between ACLR and control participants and (2)
      provide normative values for identified measures in young adult male
      multidirectional field-sport athletes. DESIGN:   Cross-sectional study. SETTING: 
      Orthopaedic hospital. PATIENTS OR OTHER PARTICIPANTS:   Young adult male
      multidirectional field-sport athletes (n = 118) who had undergone unilateral
      patellar-tendon graft ACLR at least 6 months earlier and healthy male
      participants (n = 44) with no previous knee injury. INTERVENTION(S):   Single
      legged countermovement jump (SL CMJ). MAIN OUTCOME MEASURE(S):   Three
      dimensional biomechanical analysis of the SL CMJ and mean peak concentric knee
      extension and -flexion torque using isokinetic dynamometry (ISO) were compared in
      the 2 groups. A stepwise logistic regression was carried out to identify the best
      predictors of ACLR- or control-group membership (SL CMJ height, limb symmetry
      index, peak power, joint power contribution, ISO peak torque, limb symmetry index
      variables). RESULTS:   The control group differed strongly from the ACLR group in
      isokinetic knee-extension peak torque (d = -1.33), SL CMJ performance (d > 0.4),
      and limb symmetry measures in both ISO and jump outcomes (d > 1.1). The
      combination of measures from both ISO and SL CMJ identified group membership with
      an accuracy of 89%. CONCLUSIONS:   Rehabilitation of ACLR patients may be
      complete when they achieve isokinetic knee-extension peak torque of 260% (+/-40%)
      body mass, SL CMJ performance of >17 cm (+/-4 cm), and reach-limb symmetry
      measures of >90% in both strength and jump outcomes. The outcomes in the control
      group can inform return-to-play criteria for young adult male multidirectional
      field-sport athletes after ACLR.

PMID- 30109948
TI  - Normative Performance on the Balance Error Scoring System by Youth, High School,
      and Collegiate Athletes.
AB  - CONTEXT:   Annually, more than 1 million youth athletes in the United States
      receive or are suspected of receiving a concussion. The Balance Error Scoring
      System (BESS) is the most commonly used clinical balance evaluation designed to
      provide a better understanding of the motor-control processes of individuals with
      concussion. Despite the widespread use of the BESS, a fundamental gap exists in
      applying this tool to young athletes, as normative values are lacking for this
      population. OBJECTIVE:   To determine age- and sex-specific normative values for
      the BESS in youth, high school, and collegiate athletes. DESIGN:   Cross
      sectional study. SETTING:   Local youth sport organizations, high schools, and
      colleges. PATIENTS OR OTHER PARTICIPANTS:   Student-athletes (N = 6762) completed
      preseason baseline concussion testing as part of a comprehensive concussion
      management program. Groups were youth males aged 5 to 13 years (n = 360), high
      school males aged 14 to 18 years (n = 3743), collegiate males aged 19 to 23 years
      (n = 497), youth females aged 5 to 13 years (n = 246), high school females aged
      14 to 18 years (n = 1673), and collegiate females aged 19 to 23 years (n = 243).
      MAIN OUTCOME MEASURE(S):   Errors according to the BESS specifications. RESULTS: 
      Performance on the BESS was worse ( P < .01) in youth athletes than in high
      school and collegiate athletes. In the youth and high school cohorts, females
      exhibited better scores than males ( P < .05). Sex was not a factor for
      collegiate athletes. Data from the youth cohort were further subdivided into 4
      year bins to evaluate potential motor-development differences. The error count
      was highest for 5- to 9-year-old males and decreased with age. CONCLUSIONS:  
      Performance on the BESS depended on sex and age, particularly in youth athletes.
      These sex- and age-specific normative values provide a reference to facilitate
      and unify clinical decision making across multiple providers caring for youth
      athletes with concussions.

PMID- 30109950
TI  - Assessment of Right Ventricular Function in the Research Setting: Knowledge Gaps
      and Pathways Forward. An Official American Thoracic Society Research Statement.
AB  - BACKGROUND: Right ventricular (RV) adaptation to acute and chronic pulmonary
      hypertensive syndromes is a significant determinant of short- and long-term
      outcomes. Although remarkable progress has been made in the understanding of RV
      function and failure since the meeting of the NIH Working Group on Cellular and
      Molecular Mechanisms of Right Heart Failure in 2005, significant gaps remain at
      many levels in the understanding of cellular and molecular mechanisms of RV
      responses to pressure and volume overload, in the validation of diagnostic
      modalities, and in the development of evidence-based therapies. METHODS: A
      multidisciplinary working group of 20 international experts from the American
      Thoracic Society Assemblies on Pulmonary Circulation and Critical Care, as well
      as external content experts, reviewed the literature, identified important
      knowledge gaps, and provided recommendations. RESULTS: This document reviews the
      knowledge in the field of RV failure, identifies and prioritizes the most
      pertinent research gaps, and provides a prioritized pathway for addressing these
      preclinical and clinical questions. The group identified knowledge gaps and
      research opportunities in three major topic areas: 1) optimizing the methodology
      to assess RV function in acute and chronic conditions in preclinical models,
      human studies, and clinical trials; 2) analyzing advanced RV hemodynamic
      parameters at rest and in response to exercise; and 3) deciphering the underlying
      molecular and pathogenic mechanisms of RV function and failure in diverse
      pulmonary hypertension syndromes. CONCLUSIONS: This statement provides a roadmap
      to further advance the state of knowledge, with the ultimate goal of developing
      RV-targeted therapies for patients with RV failure of any etiology.

PMID- 30109951
TI  - Need for fixed combination therapy in type-2 diabetes: Findings from the SMART
      study.

PMID- 30109952
TI  - Adipokine profile as a novel screening method for cardiometabolic disease: Help
      or hindrance?

PMID- 30109953
TI  - Application of the Medical Neighborhood to Children with Severe Obesity.
AB  - BACKGROUND: Growth in the prevalence of severe pediatric obesity and tertiary
      care pediatric weight management programs supports the application of chronic
      disease management models to the care of children with severe obesity. One such
      model, the medical neighborhood, aims to optimize care coordination between
      primary and tertiary care by applying principles of the Patient-Centered Medical
      Home to all providers. METHODS: An exploration of the literature was performed
      describing effective programs, approaches, and coordinated care models applied to
      pediatric weight management and other chronic conditions. RESULTS: Though there
      was a paucity of literature discovered with applications specific to pediatric
      weight management, relevant disease management and care coordination approaches
      were found. Proposed applications to the care of children with severe obesity can
      be made. CONCLUSION: The application of the medical neighborhood framework, with
      its inclusion of healthcare and community partners, may optimize the management
      of children with severe obesity.

PMID- 30109954
TI  - Hepatocellular Carcinoma: In Vivo Evaluation of Water Percentage as a Prognostic
      Biomarker Using Magnetic Resonance Imaging 3D-VIBE Multiecho Dixon.
AB  - INTRODUCTION: It is urgent to find an effective method to diagnose and prognose
      early hepatocellular carcinoma (HCC). The purpose of this study was to
      investigate the correlation between HCC histological degree and water percentage
      (WP) obtained from magnetic resonance imaging 3D-VIBE multiecho Dixon, and to
      evaluate the feasibility of WP in the postoperative prediction of early HCC
      recurrence. METHODS AND MATERIALS: From June 2016 to July 2017, 76 patients with
      diagnostic HCC all underwent 3D-VIBE Multiecho Dixon and ultrahigh b value
      diffusion-weighted imaging (DWI) examination. Freehand regions of interests were
      placed to measure the WP and apparent diffusion coefficient (ADC) value. The
      Edmondson-Steiner (E-S) grades proved by histopathological results were acquired
      from all patients. Comparisons between mean WP and ADC with E-S grades I-IV were
      performed using Kruskal-Wallis test and one-way ANOVA. Least Significant
      Difference t-test (LSD-t test) was applied to compare particular pairs of mean
      ADC value between every two E-S groups. Correlations between WP, ADC, and E-S
      grades were assessed by Spearman's rank correlation test. The Mann-Whitney U test
      was utilized to compare the difference of mean WP between recurrence and
      nonrecurrence group. The receiver operating characteristic (ROC) curves were
      calculated to estimate the diagnostic effect of 3D-VIBE Multiecho Dixon and
      ultrahigh b value DWI to HCC. Kaplan-Meier method was used to evaluate the
      recurrence free survival (RFS) after surgical resection. RESULTS: Mean WP values
      among groups E-S I to IV were 91.8%, 95.2%, 96.4%, and 97.7%, respectively. A
      positive correlation was exhibited between the WP and histopathological E-S
      grades (r = 0.480, p < 0.01). The ADC values based on E-S grades were 0.93, 0.82,
      0.74, and 0.62 * 10-3 mm2/s, respectively. Significant differences were found
      between every two E-S groups (p < 0.01), and a negative correlation between ADC
      and E-S grades (r = -0.784, p = 0.000) was observed. Mean value of WP was 97.2%
      in recurrence group and 94.6% in nonrecurrence group (p < 0.01). The optimal
      cutoff value was 95.7%. The maximal area under the ROC curve was 0.747 +/- 0.06
      for WP, 0.631 +/- 0.07 for ADC, and 0.753 +/- 0.06 for the combination of WP and
      ADC. Mean RFS was 18.1 months in the lower WP and 10.7 months in higher WP group
      (p < 0.01). CONCLUSIONS: WP can be used as a potential biomarker for the
      diagnosis and prognosis of HCC. A lower value of WP may imply a better outcome in
      patients after surgical resection.

PMID- 30109955
TI  - Inclusion of Sleep Promotion in Family-Based Interventions To Prevent Childhood
      Obesity.
AB  - Sleep promotion in childhood may reduce the risk of obesity, but little is known
      of its inclusion in family-based interventions. This study examines the
      proportion and context of family-based interventions to prevent childhood obesity
      that promote child sleep. We drew on data from a recent systematic review and
      content analysis of family-based interventions for childhood obesity prevention
      published between 2008 and 2015, coupled with new data on sleep promotion
      strategies, designs, and measures. Out of 119 eligible family-based interventions
      to prevent childhood obesity, 24 (20%) promoted child sleep. In contrast, 106
      (89%) interventions targeted diet, 97 (82%) targeted physical activity, and 63
      (53%) targeted media use in children. Most interventions that promoted sleep were
      implemented in clinics (50%) and home-based settings (38%), conducted in the
      United States (57%), and included children 2-5 years of age (75%). While most
      interventions utilized a randomized controlled design (70%), only two examined
      the promotion of sleep independent of other energy-balance behaviors in a
      separate study arm. Sleep was predominately promoted by educating parents on
      sleep hygiene (e.g., age-appropriate sleep duration), followed by instructing
      parents on responsive feeding practices and limiting media use. One intervention
      promoted sleep by way of physical activity. A large number promoted sleep by way
      of bedtime routines. Most interventions measured children's sleep by parent
      report. Results demonstrate that sleep promotion is underrepresented and variable
      in family-based childhood obesity interventions. While opportunities exist for
      increasing its integration, researchers should consider harmonizing and being
      more explicit about their approach to sleep promotion.

PMID- 30109956
TI  - Angelica sinensis Supercritical Fluid CO2 Extract Attenuates D-Galactose-Induced
      Liver and Kidney Impairment in Mice by Suppressing Oxidative Stress and
      Inflammation.
AB  - Angelica sinensis (AS, Danggui in Chinese) is an important herbal component of
      various traditional formulae for the management of asthenia and its tonic
      effects. Although AS has been shown to ameliorate cognitive damage and nerve
      toxicity in D-galactose (D-gal)-elicited senescent mice brain, its effects on
      liver and kidney injury have not yet been explored. In this work, mice were
      subjected to hypodermic injection with D-gal (200 mg/kg) and orally gavaged with
      AS (20, 40, or 80 mg/kg) once a day for 8 successive weeks. Results revealed that
      AS significantly improved liver and kidney function as assessed by organ index
      and functional parameters. In addition, AS pretreatment effectively ameliorated
      the histological deterioration. AS attenuated the MDA level and markedly enhanced
      the activities and gene expressions of antioxidative enzymes, namely Cu, Zn-SOD,
      CAT, and GPx. Furthermore, AS markedly inhibited the D-gal-mediated increment of
      expressions of inflammatory cytokines iNOS, COX-2, IkappaBalpha, p-IkappaBalpha,
      and p65 and promoted the IkappaBalpha expression level in both hepatic and renal
      tissues. In sum, AS pretreatment could effectively guard the liver and kidney of
      mice from D-gal-induced injury, and the underlying mechanism was deemed to be
      intimately related to attenuating oxidative response and inflammatory stress.

PMID- 30109957
TI  - Effects of In-Feed Chlortetracycline Prophylaxis in Beef Cattle on Antimicrobial
      Resistance Genes.
AB  - Approximately 20% of U.S. beef cattle receive prophylactic in-feed administration
      of chlortetracycline (CTC) to reduce bovine respiratory disease (BRD) incidence
      during the transition into feedlots. To determine the impact of prophylaxis on
      selected antimicrobial resistance genes (ARGs), 300 beef cattle were placed into
      10 pens (30 head/pen). Five "CTC group" pens received in-feed CTC (10 mg/lb of
      body weight/d) from the fifth to ninth day after feedlot arrival, whereas the
      five "Control group" pens received no CTC. Fecal swabs and pen surface materials
      were collected for metagenomic DNA isolation on five sample occasions: arrival at
      the feedlot, 5 d posttreatment (dpt), and 27, 75, and 117 dpt. For each sample
      occasion, fecal samples and pen surface material samples were pooled by pen.
      Quantitative polymerase chain reaction was used to determine the abundances of 10
      ARGs. Due to low detection percentages (%D) and quantification percentages (%Q),
      the abundances of five ARGs were not analyzed: aac(6')-Ie-aph(2'') (%D = 43%, %Q
      = 4%), blaCMY-2 (%D = 41%, %Q = 0%), blaCTX-M (%D = 0%, %Q = 0%), blaKPC-2 (%D =
      21%, %Q = 16%), and mecA (%D = 4%, %Q = 0%). The %D and %Q for the ARGs aadA1,
      erm(B), tet(A), tet(B), and tet(M) were >=98% and >=90%, respectively. The
      abundances of aadA1, erm(B), tet(A), tet(B), and tet(M) resistance genes did not
      differ (p > 0.05) between the CTC and control groups at any sampling time for
      feces or pen surface material. Although only 10 ARGs were examined in this study,
      the results suggest that a single 5-d in-feed CTC prophylaxis of beef cattle to
      prevent BRD has a negligible impact on the abundances of ARGs.

PMID- 30109959
TI  - The efficacy of oral acyclovir during early course of pityriasis rosea: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Acyclovir has been reported as a potential therapy for pityriasis
      rosea (PR) in several clinical trials on the basis of evidence of the involvement
      of human herpes viruses 6 and 7. OBJECTIVE: We evaluated the efficacy of
      acyclovir for abating PR skin lesions within a fixed period. METHODS: We searched
      4 databases for clinical trials that used oral acyclovir to treat PR and
      performed systematic review and meta-analysis to determine oral acyclovir's
      effect on skin lesions on the 14th day after commencing treatment. RESULTS: Five
      clinical trials including four randomized controlled trials were identified that
      compared the effects of oral acyclovir (n = 133) and nonacyclovir (n = 140) in
      patients with PR. Oral acyclovir significantly reduced erythema (odds ratio [OR]
      11.30; 95% CI = 5.70-22.41; p < .01) and limited lesion formation (OR 8.67; 95%
      CI = 3.29-22.81; p < .01) compared with nonacyclovir treatment on the 14th day.
      These results were in agreement with the results of subgroup analysis of only
      high-dose oral acyclovir treatment and randomized controlled trials. CONCLUSION:
      Oral acyclovir may be a relatively safe and effective treatment in the early
      course of PR, and patients with PR may achieve faster symptoms control with
      acyclovir.

PMID- 30109960
TI  - The use of methotrexate for treating childhood atopic dermatitis: a multicenter
      retrospective study.
AB  - BACKGROUND: Atopic dermatitis is a chronic inflammatory skin disease.
      Methotrexate is an off-label systemic agent for treating uncontrolled atopic
      dermatitis. OBJECTIVE: This study assessed the safety and efficacy of
      methotrexate in pediatric patients with atopic dermatitis. METHODS: This
      multicenter, retrospective study assessed pediatric patients with atopic
      dermatitis who were treated with methotrexate. RESULTS: Medical records of 26
      pediatric patients with atopic dermatitis were reviewed. All the patients had
      Investigator Global Assessment (IGA) scores of 3-4 and had received systemic
      therapy before receiving methotrexate. In all, 53.85% patients showed clinical
      improvement at 3 and 6 months after methotrexate initiation. The IGA scores of
      the patients decreased significantly at 3 months after methotrexate initiation
      compared with those at baseline; moreover, the IGA scores of the patients at 6
      months after methotrexate initiation were lower than those at 3 months after
      methotrexate initiation. In all, 54% study patients are still undergoing
      methotrexate treatment. Median satisfaction rate with methotrexate was 7.5/10.
      However, 10.35% patients developed adverse events, of which only one patient
      discontinued the treatment. CONCLUSIONS: Our results indicate that methotrexate
      is a tolerable and effective agent for treating refractory childhood atopic
      dermatitis.

PMID- 30109958
TI  - Foodborne and Food-Handler Norovirus Outbreaks: A Systematic Review.
AB  - Norovirus (NoV) is the commonest cause of gastrointestinal disease in the United
      Kingdom and in many developed countries, causing diarrhea and vomiting in
      millions of cases worldwide annually. Transmission is most often mediated from
      person to person. NoV infection has, however, additionally been associated with
      the consumption of food, either through the consumption of food contaminated at
      source such as seafood, berries, and salad, or as a consequence of the foodstuff
      being contaminated in some way by a food handler during processing or serving. A
      systematic review of outbreaks attributed to NoV between January 2003 and July
      2017 was conducted to assess the contribution of food handlers to the burden of
      NoV, and to identify foods commonly associated with NoV outbreaks. A total of
      3021 articles were screened, of which 27 met the definition of confirmed
      foodborne outbreaks and 47 met the criteria for definite food-handler NoV
      outbreaks. Of all food types, shellfish were implicated in the greatest number of
      definite foodborne outbreaks. Food handlers contributed to definite food-handler
      outbreaks involving a diverse range of foodstuffs and in a wide variety of
      settings, including weddings and military establishments. More genotypes of NoV
      were found in people who were ill than in samples from food and food handlers.
      The potential for both food products and food handlers to contribute to the
      burden of NoV infection is demonstrated conclusively.

PMID- 30109961
TI  - Women Need Less Judgment and More Support to Access Contraception.

PMID- 30109962
TI  - USP14 inhibitors as potential anticancer agents.

PMID- 30109963
TI  - The Association Between Cyberbullying, School Bullying, and Suicidality Among
      Adolescents.
AB  - BACKGROUND: Bullying and suicidality are serious worldwide problems with negative
      effects on the young population and therefore international comparisons in this
      field are of paramount importance. AIMS: To analyze the prevalence of bullying
      and cyberbullying and their association with suicidal behavior among school-aged
      children in Israel, Lithuania, and Luxembourg. METHOD: In total, 3,814 15-year
      olds from schools in Israel, Lithuania, and Luxembourg were surveyed in the
      Health Behavior in School-Aged Children (HBSC) cross-national survey in 2013/2014
      using standardized anonymous questionnaires. Data analysis employed logistic
      regression and structural equation modeling (SEM). RESULTS: In all, 6.5% of the
      adolescents reported being cyberbullied, 15.6% reported being bullied at school.
      In the previous 12 months, 38.6% reported experiencing emotions that stopped them
      from doing their usual activities, 17.8% considered attempting suicide, 12.0%
      made a suicide plan, and 9.5% attempted suicide. Victims of cyberbullying and
      school bullying had a significantly higher risk of suicidal ideations, plans, and
      attempts. The SEM analysis confirmed a significant overall effect of bullying on
      adolescent suicidality. The strongest effect was seen among Israeli students.
      LIMITATIONS: The prevalence estimates were obtained by self-report. CONCLUSION:
      The prevalence of adolescent cyberbullying, school bullying, and suicidal
      behavior is relatively high in Israel, Lithuania, and Luxembourg. Cyberbullying
      is a strong predictor of adolescent suicidality.

PMID- 30109964
TI  - Rethinking Suicidal Behavior Disorder.
AB  - BACKGROUND: It is a peculiar fact that the deadliest psychiatric disturbance -
      suicidality - cannot be formally diagnosed. Suicidal behavior disorder (SBD), a
      condition for further study in the DSM-5, is the field's first attempt to capture
      suicidality in a diagnosis. AIMS: To provoke discussion about the standing of
      suicidality as a diagnosable psychiatric condition. METHOD: I present pragmatic
      and conceptual rationales for why a diagnosis of suicidality is clinically useful
      but conclude that SBD does little to aid clinicians in assessing suicidality's
      symptoms, planning treatment, or monitoring progress. RESULTS: To improve the
      clinical utility of SBD, I re-conceptualize it from the vantage point of
      descriptive psychiatry. I hypothesize that this revised SBD is an independent,
      episodic, and frequently co-occurring condition and propose new cognitive,
      affective, and behavioral criteria that more completely capture the phenomenology
      of suicidality. CONCLUSION: The revised SBD is a starting place for dialogue
      about whether a clinically significant presentation of suicidality is a mental
      illness and, if it is, what its defining features should be.

PMID- 30109965
TI  - Is There a Need for LGBT-Specific Suicide Crisis Services?
AB  - BACKGROUND: Lesbian, gay, bisexual, and transgender (LGBT) youth are more than
      twice as likely to attempt suicide than their peers. Although LGBT-specific
      crisis services have been developed, little is known about the need for these
      services beyond that of general lifeline services. AIMS: The present study sought
      to (a) describe the primary reasons for calling a specialized provider as opposed
      to another and (b) examine sociodemographic differences in the primary reason by
      race, ethnicity, gender, age, and sexual orientation. METHOD: Data from 657 youth
      who sought crisis services from an LGBT-specific national service provider in the
      United States were assessed. Logistic regression models assessed demographic
      differences. Thematic analysis of open-ended responses regarding reasons for
      choosing this LGBT-specific crisis service provider followed a consensus model.
      RESULTS: Most respondents indicated they either would not have contacted another
      helpline (26%) or were not sure (48%). Nearly half (42%) indicated they called
      specifically because of LGBT-affirming counselors, a reason more commonly
      reported by gender minority (transgender and gender nonbinary) and queer or
      pansexual youth than cisgender, gay, or lesbian youth. CONCLUSION: LGBT-specific
      crisis services appear to play an important role in suicide prevention. Further
      research is needed to understand the use of culturally tailored suicide
      prevention approaches.

PMID- 30109966
TI  - Comparing Indicators of Suicidality Among Users in Different Types of
      Nonprofessional Suicide Message Boards.
AB  - BACKGROUND: Little is known about linguistic differences between nonprofessional
      suicide message boards that differ in regard to their predominant attitude to
      suicide. AIMS: To compare linguistic indicators potentially related to
      suicidality between anti-suicide, neutral, and pro-suicide message boards, and
      between the types of posters (primary posters, who initiate the thread, and the
      respective respondents). METHOD: In all, 1,200 threads from seven German-language
      nonprofessional suicide message boards were analyzed using the software
      Linguistic Inquiry and Word Count (LIWC) with regard to wording related to
      suicidal fantasies, aggression, and indicators of so-called suicidal
      constriction. Data were analyzed with ANOVA. RESULTS: There were fewer words
      related to affective, social, cognitive, and communicative processes in pro
      suicide message boards than in other boards. Death-related wording and aggression
      as well as tentative wording appeared more prevalent in pro-suicide boards.
      LIMITATIONS: Complex language structures cannot be analyzed with LIWC.
      CONCLUSION: The results suggest fewer emotion words and wording related to social
      circumstances among primary posters and respondents in pro-suicide boards as
      compared with other boards, and a higher use of death- and aggression-related
      words. These findings might signal a higher degree of suicidality or sheer
      differences in matters of interest or social desirability. The differences
      require attention in practice and research.

PMID- 30109967
TI  - Comparing the Effectiveness of Brief Versus In-Depth Gatekeeper Training on
      Behavioral Outcomes for Trainees.
AB  - BACKGROUND: A common suicide prevention strategy is training gatekeepers to
      identify at-risk individuals and refer them to services. AIMS: The study aimed to
      examine whether differences in training outcomes were observed for brief versus
      in-depth gatekeeper trainings for trainees from varied professional settings
      while controlling for differences in trainee characteristics and community
      context. METHOD: Trainees' identification and referral behavior 3 months after
      gatekeeper training was compared with a sample of respondents matched on
      individual- and community-level variables using propensity score-based
      techniques. The value was estimated, in terms of additional identification and
      associated costs, of adopting in-depth training. RESULTS: A higher proportion of
      trainees who participated in in-depth trainings from K-12 and community settings
      identified at-risk youth, and a higher proportion of in-depth trainees from
      mental health settings referred youth to services compared with participants of
      brief trainings from the same setting and with similar characteristics. The
      effect of training type on outcomes varied by professional role and community
      context. LIMITATIONS: Self-report measures were used to assess outcomes. Similar
      measures are used in other studies; their validity has not been conclusively
      established. CONCLUSION: Findings suggest certain individuals may benefit from in
      depth training more than others, which favors targeting this intervention to
      particular gatekeepers.

PMID- 30109968
TI  - Editorial.

PMID- 30109969
TI  - Antimicrobial Treatment of Escherichia coli and Staphylococcus aureus in Herbal
      Tea Using Low-Temperature Plasma.
AB  - A low-pressure capacitively coupled discharge was used to study antimicrobial
      treatment in herbal tea. Ambient air with a relative humidity of 40% was used as
      a precursor gas and fed into the chamber via a perforated power electrode. An
      electrical discharge plasma was produced at a radio frequency of 10 kHz and power
      of 80 W. The operating pressure during treatment was kept constant at 260 Pa. The
      target microorganisms, Escherichia coli and Staphylococcus aureus, isolated from
      the herbal tea were inoculated on nutrient agar petri dishes and exposed to the
      plasma for 0.5, 1.0, 1.5, and 2.0 min. All treatments were carried out in
      triplicate for different exposure times to calculate the D-value by the
      enumeration method. D-values of 0.73 and 0.67 min were obtained corresponding to
      E. coli and S. aureus reduction, respectively.

PMID- 30109970
TI  - Navel Orange Peel Essential Oil To Control Food Spoilage Molds in Potato Slices.
AB  - The aim of this study was to investigate the efficacy of navel orange, Citrus
      sinensis (L.) Osbeck, peel essential oil (NOPEO) for inhibiting spoilage fungi in
      potato slices. Sixteen different components accounting for 99.79% of the
      headspace components of NOPEO were identified by gas chromatography-mass
      spectrometry. d-Limonene was the major component of NOPEO. Antifungal activity of
      NOPEO was tested in vitro and in vivo against four foodborne fungi. A MIC of
      NOPEO against the four fungal species was 9.40 MUL/mLair. NOPEO provided about
      74, 74, 73, and 69% protection against Aspergillus niger, Mucor wutungkiao,
      Penicillium funiculosum, and Rhizopus oryzae at 2.00 MUL/mLair concentration,
      respectively. NOPEO has been demonstrated to significantly improve the
      microbiological quality of potato slices.

PMID- 30109971
TI  - Effect of Succinic Acid on Elimination of Salmonella in Chicken Meat.
AB  - The aim of this study was to determine the effect of selected concentrations of
      succinic acid on the survival of Salmonella on microbiological media and on the
      surfaces of chicken carcasses. Samples were inoculated with Salmonella serovars
      Enteritidis, Typhimurium, Hadar, Infantis, and Virchow. Each strain from each
      dilution was plated on nutrient agar without chemical substances (pH 6.75,
      control) or with 0.02% (pH 5.73), 0.05% (pH 4.77), 0.1% (pH 4.42), or 0.25% (pH
      3.90) succinic acid. The addition of 0.25% succinic acid in agar medium
      completely inhibited the growth of all Salmonella strains tested. The 150 samples
      of broiler chicken breasts were immersed for 2 min in 80 mL of a 107 CFU/mL
      Salmonella cocktail. The samples were then transferred to sterile beakers with
      250 mL of 2 and 5% succinic acid for 5 min. With 2% succinic acid, Salmonella
      reductions (compared with the control) were 1.27 to 1.47 log CFU/g. With 5%
      succinic acid, reductions were 2.00 to 3.20 log CFU/g. The results indicate that
      it is possible to reduce the level of Salmonella on broiler chicken carcasses by
      immersing them in a 2% succinic acid solution.

PMID- 30109972
TI  - A Comparative Study of the Susceptibility of Listeria Species to Sanitizer
      Treatments When Grown under Planktonic and Biofilm Conditions.
AB  - Listeria species are ubiquitous in nature and can adapt to survive in a variety
      of niches, including food processing environments. Listeria species that colonize
      these environments may also have the potential to persist. Food safety strategies
      designed to manage these niches include regular cleaning and disinfection with
      proven sanitizers containing biocide-active compounds. Typically, these
      sanitizers are effective against bacteria growing under planktonic conditions,
      but their efficacy may be compromised when bacteria are contained in biofilms.
      The susceptibility of persistent Listeria isolates, i.e., those capable of
      forming biofilms, to a selection of sanitizers was investigated. A quaternary
      ammonium compound-based sanitizer was the biocide most effective against
      planktonic bacteria, with a MIC of 0.0015 to 0.006%. In contrast, ethanol-based
      sanitizers were the least effective. Although, no triclosan tolerance was
      observed for planktonic Listeria isolates, triclosan was the only biocide that
      resulted in a significant biomass reduction. Differences between Listeria species
      were observed; L. monocytogenes and L. welshimeri biofilms were more tolerant to
      quaternary ammonium compound-based sanitizers than were L. innocua biofilms.
      These findings extend our understanding of the application of commonly used
      sanitizers in the food industry and the efficacy of these sanitizers against
      Listeria species and their associated biofilms.

PMID- 30109973
TI  - Effect of Age and Comorbidities on Short- and Long-Term Results in Patients
      Undergoing Laparoscopic Curative Resection for Rectal Cancer.
AB  - BACKGROUND AND AIM: Conflicting findings have been reported in older patients
      undergoing laparoscopic surgery for rectal cancer. The aim of this study was to
      evaluate the effects of age and comorbidities on short- and long-term results of
      patients undergoing laparoscopic curative resection for rectal cancer (LCRRC).
      MATERIALS AND METHODS: We retrospectively evaluated all 173 consecutive patients
      undergoing LCRRC at our unit (June 2005-September 2015). They were divided into
      two age groups as follows: <75 (n = 122) and >=75 (n = 51) years. Comorbidities
      were evaluated using American Society of Anesthesiologists (ASA) score, Charlson
      Comorbidity Index (CCI), and age-related Charlson Comorbidity Index (ACCI).
      RESULTS: Tumor characteristics were similar in the two groups. Comorbidity status
      (ASA, CCI, ACCI) was worse in elderly patients. Type of surgery performed was
      similar in the two groups. Medical complications were significantly higher in
      elderly (10.7% versus 29.4%, P = .006), while surgical complications were
      similar. Postoperative stay was longer in older patients (13 days versus 9 days,
      P = .0007). Multivariable analysis identified older age, higher CCI, and longer
      operative time as independent predictors of morbidity. Five years overall
      survival and disease-free survival were 49% and 43% in older and 84% and 77% in
      younger group (P < .0001). Multivariable analysis identified age, CCI, tumor,
      node, metastasis stage, and postoperative morbidity as independent risk factors
      for overall and disease-free survival. CONCLUSIONS: LCRRC achieves excellent
      short- and long-term results, but age and comorbidities may significantly affect
      postoperative morbidity and survival.

PMID- 30109974
TI  - Evaluation of Epworth Sleepiness Scale to Predict Obstructive Sleep Apnea in
      Morbidly Obese Patients and Increasing Its Utility.
AB  - INTRODUCTION: Studies have shown that Epworth sleepiness scale (ESS) is not a
      good tool to predict obstructive sleep apnea (OSA). However, data regarding the
      accuracy of ESS in the prediction of OSA among morbidly obese patients are
      scarce. METHODS: The study involved a retrospective review of the charts of the
      consecutive patients who underwent bariatric surgery at a tertiary care teaching
      hospital. All the patients underwent polysomnography (PSG) and undertook the ESS
      questionnaire. The sensitivity and specificity of ESS were calculated based on
      its correlation with the PSG findings. Furthermore, a new score was devised to
      improve the utility of ESS to predict OSA. RESULTS: A total of 232 consecutive
      patients from January 2014 to July 2017 were included in the study. The mean age
      and body mass index (BMI) were 40.5 +/- 11.8 years and 47.6 +/- 7.3 kg/m2,
      respectively. Among the 162 patients who had an ESS <10, 57.4% had moderate-to
      severe OSA. The sensitivity of ESS to predict moderate-to-severe OSA was found to
      be 38.8% and the positive predictive value was 84.2% (positive likelihood ratio
      2.82, 95% confidence interval = 1.57-5.06). A predictive score was identified as
      0.031Age (years) +0.039BMI (kg/m2) + 0.038ESS + Gender (1 for male, 0 for
      female). The score had a sensitivity of 80% at a cutoff of 3.3. CONCLUSIONS:
      Among the morbidly obese, ESS is a poor predictor of OSA. Its utility as a tool
      for prediction of moderate-to-severe OSA can be improved by use of a new formula
      incorporating age, gender, and BMI beside ESS.

PMID- 30109975
TI  - In Vitro Bactericidal Activity of Trimethoprim-Sulfamethoxazole/Colistin
      Combination Against Carbapenem-Resistant Klebsiella pneumoniae Clinical Isolates.
AB  - Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as a formidable
      health challenge in recent years owing to the shortage of effective antibiotics.
      Colistin is the last and sometimes the only therapeutic option for CRKP
      infections. Unfortunately, resistance to colistin monotherapy is likely to
      develop. CRKP in China reportedly exhibit low rates of resistance to trimethoprim
      sulfamethoxazole. The aim of this study was to evaluate the in vitro efficacy of
      trimethoprim-sulfamethoxazole in combination with colistin against four CRKP
      clinical isolates. The trimethoprim-sulfamethoxazole/colistin combination rapidly
      killed all four of the tested isolates after 2 h up to 24 h. Trimethoprim
      sulfamethoxazole is one of the few remaining antimicrobials with some activity
      against CRKP. In particular, combined with colistin, trimethoprim
      sulfamethoxazole might be promising for the treatment of CRKP infections.

PMID- 30109976
TI  - Verticillium Wilt Caused by Verticillium dahliae and V. nonalfalfae in Potato in
      Northern China.
AB  - Potato (Solanum tuberosum L.) is one of the most important staple foods in many
      parts of the world including China. In recent years, Verticillium wilt has become
      a severe threat to potato production in China. During 2015 to 2016, 287 samples
      of symptomatic potato plants were collected from 15 counties in five provinces
      from northern China. One hundred and eighty-seven Verticillium-like colonies were
      isolated from these samples and identified to species based on cultural and
      morphological characteristics, and multigene phylogeny based on the partial
      sequences of actin (ACT), elongation factor 1-alpha (EF1alpha), glyceraldehyde-3
      phosphate dehydrogenase (GPD), and tryptophan synthase (TS) genes. A consensus
      rooted most parsimonious phylogenetic tree was generated from the data. One
      hundred and fifteen isolates comprising 61.5% of the total were identified as
      Verticillium dahliae, and the remaining 38.5% of the isolates were identified as
      V. nonalfalfae. V. dahliae was widely distributed in Shaanxi (84.1%), Inner
      Mongolia (76.7%), Gansu (12.8%), and Qinghai (100%, representing a single
      isolate). V. dahliae was not recovered from the samples in Ningxia. V.
      nonalfalfae dominated the collections from Gansu (87.2%) and Ningxia (100%) but
      was also recovered from Shaanxi (15.9%) and Inner Mongolia (23.3%) at lower
      frequencies. Neither V. albo-atrum nor V. alfalfae was recovered from the sampled
      areas. The V. nonalfalfae isolates were predominantly isolated from the samples
      collected from altitudes above 1,800 m, and in contrast, V. dahliae isolates were
      mainly recovered from fields sampled below 1,800 m. The optimum temperature for
      the colony growth of V. nonalfalfae was lower (20 degrees C) than that for V.
      dahliae (25 degrees C). Pathogenicity tests demonstrated that V. dahliae and V.
      nonalfalfae were both pathogens of potato Verticillium wilt, with V. dahliae
      isolates exhibiting higher virulence than V. nonalfalfae isolates regardless of
      the collection area of the species. This is the first documentation of V.
      nonalfalfae infecting S. tuberosum in China and the higher altitudes associated
      with infections of V. nonalfalfae anywhere in the world.

PMID- 30109977
TI  - Virological and Serological Responses of Sheep and Cattle to Experimental
      Schmallenberg Virus Infection.
AB  - Schmallenberg virus (SBV) is an orthobunyavirus in the Simbu serogroup that
      emerged in Germany in late 2011 and was mostly associated with a mild transient
      disease of sheep and cattle. SBV is transmitted by biting midges (Culicoides
      species) and causes abortions, stillbirths, and congenital defects in naive
      pregnant ruminants. Two separate studies were conducted with a primary objective
      of better understanding the virological and serological responses of sheep and
      cattle to different SBV isolates after experimental infection. The second
      objective was to produce immunoreagents and challenge materials for use in future
      vaccine and diagnostics research. These studies were carried out using the
      following infectious inocula: (i) infectious serum (IS) (ii) cell culture-grown
      virus, and (iii) infectious lamb brain homogenate. The responses were assessed in
      both species throughout the course of the experiment. SBV RNA in serum (RNAemia)
      was detected as early as 2 (in sheep) and 3 (in cattle) days postinfection (dpi)
      and peaked on 3 and 4 dpi in cattle and sheep, respectively. Cattle had higher
      levels of RNAemia compared with sheep. Experimental infection with IS resulted in
      the highest level of RNAemia in both species followed by cell culture-grown
      virus. A delayed, low level RNAemia was detected in cattle inoculated with
      infectious sheep brain. Isolation of SBV was only possible from 4 dpi sera from
      all cattle inoculated with IS and one sheep inoculated with cell culture-derived
      virus. SBV neutralizing antibodies were first detected on 14 dpi in both species.
      No specific gross and microscopic lesions were observed in either study. In
      conclusion, these studies highlight not only the difference in viremia and anti
      SBV antibody level against the different SBV isolates, but also the extent of the
      response in the two host species.

PMID- 30109978
TI  - Transcriptomic analysis with the progress of symbiosis in 'crack-entry' legume
      Arachis hypogaea highlights its contrast with 'infection thread' adapted legumes.
AB  - In root-nodule symbiosis, rhizobial invasion and nodule organogenesis is host
      controlled. In most legumes, rhizobia enter through infection-threads and nodule
      primordium in the cortex is induced from a distance. But in dalbergoid legumes
      like Arachis hypogaea, rhizobia directly invade cortical cells through epidermal
      cracks to generate the primordia. Herein we report the transcriptional dynamics
      with the progress of symbiosis in A. hypogaea at 1dpi: invasion; 4dpi: nodule
      primordia; 8dpi: spread of infection in nodule-like structure; 12dpi: immature
      nodules containing rod-shaped rhizobia; and 21dpi: mature nodules with spherical
      symbiosomes. Expression of putative orthologue of symbiotic genes in 'crack
      entry' legume A. hypogaea was compared with infection thread adapted model
      legumes. The contrasting features were (i) higher expression of receptors like
      LYR3, EPR3 as compared to canonical NFRs (ii) late induction of transcription
      factors like NIN, NSP2 and constitutive high expression of ERF1, EIN2, bHLH476
      and (iii) induction of divergent pathogenesis responsive PR-1 genes.
      Additionally, symbiotic orthologues of SymCRK, ROP6, RR9, SEN1 and DNF2 were not
      detectable and microsynteny analysis indicated the absence of RPG homologue in
      diploid parental genomes of A. hypogaea. The implications are discussed and a
      molecular framework that guide 'crack-entry' symbiosis in A. hypogaea is
      proposed.

PMID- 30109980
TI  - AAID Foundation-Caring for Those Who Have Given and Sacrificed for Our Country.

PMID- 30109979
TI  - Chemokine CXCL10 and Coronavirus-Induced Neurologic Disease.
AB  - Chemokines (chemotactic cytokines) are involved in a wide variety of biological
      processes. Following microbial infection, there is often robust chemokine
      signaling elicited from infected cells, which contributes to both innate and
      adaptive immune responses that control growth of the invading pathogen. Infection
      of the central nervous system (CNS) by the neuroadapted John Howard Mueller (JHM)
      strain of mouse hepatitis virus (JHMV) provides an excellent example of how
      chemokines aid in host defense as well as contribute to disease. Intracranial
      inoculation of the CNS of susceptible mice with JHMV results in an acute
      encephalomyelitis characterized by widespread dissemination of virus throughout
      the parenchyma. Virus-specific T cells are recruited to the CNS, and control
      viral replication through release of antiviral cytokines and cytolytic activity.
      Sterile immunity is not acquired, and virus will persist primarily in white
      matter tracts leading to chronic neuroinflammation and demyelination. Chemokines
      are expressed and contribute to defense as well as chronic disease by attracting
      targeted populations of leukocytes to the CNS. The T cell chemoattractant
      chemokine CXCL10 (interferon-inducible protein 10 kDa, IP-10) is prominently
      expressed in both stages of disease, and serves to attract activated T and B
      lymphocytes expressing CXC chemokine receptor 3 (CXCR3), the receptor for CXCL10.
      Functional studies that have blocked expression of either CXCL10 or CXCR3
      illuminate the important role of this signaling pathway in host defense and
      neurodegeneration in a model of viral-induced neurologic disease.

PMID- 30109981
TI  - Molecular survey of coccidian infections of the side-blotched lizard Uta
      stansburiana on San Benito Oeste Island, Mexico.
AB  - Blood parasites are found in many vertebrates, but the research on blood
      parasites of lizards is still at its onset. We analyzed blood samples from side
      blotched lizards Uta stansburiana from San Benito Oeste Island, Mexico, to test
      for the presence of hemoparasites. We found a high prevalence (23 out of 27
      samples) of a blood parasite of the genus Lankesterella (Coccidia, Eimeriorina,
      Lankesterellidae) according to phylogenetic analyses of the parasite 18S rRNA
      gene. Similar parasites (97-99% similarity) have recently been described for Uta
      stansburiana from California. The parasite 18S rRNA gene showed high variability,
      both within San Benito and compared to California. The next closest matches of
      the parasite DNA with 97-98% similarity included a range of different genera
      (Lankesterella, Schellackia, Eimeria, Isospora and Caryospora). A high
      uncertainty in the deeper branches of the phylogenetic trees, and many missing
      links in genetic network analysis, were in line with previous suggestions that
      the coccidians are an understudied group with large knowledge gaps in terms of
      their diversity and taxonomy. Further studies are needed to resolve the
      evolutionary relationships within the Eimeriorina.

PMID- 30109982
TI  - Structural basis for Scc3-dependent cohesin recruitment to chromatin.
AB  - The cohesin ring complex is required for numerous chromosomal transactions
      including sister chromatid cohesion, DNA damage repair and transcriptional
      regulation. How cohesin engages its chromatin substrate has remained an
      unresolved question. We show here, by determining a crystal structure of the
      budding yeast cohesin HEAT-repeat subunit Scc3 bound to a fragment of the Scc1
      kleisin subunit and DNA, that Scc3 and Scc1 form a composite DNA interaction
      module. The Scc3-Scc1 subcomplex engages double-stranded DNA through a conserved,
      positively charged surface. We demonstrate that this conserved domain is required
      for DNA binding by Scc3-Scc1 in vitro, as well as for the enrichment of cohesin
      on chromosomes and for cell viability. These findings suggest that the Scc3-Scc1
      DNA-binding interface plays a central role in the recruitment of cohesin
      complexes to chromosomes and therefore for cohesin to faithfully execute its
      functions during cell division.

PMID- 30109983
TI  - Acute control of the sleep switch in Drosophila reveals a role for gap junctions
      in regulating behavioral responsiveness.
AB  - Sleep is a dynamic process in most animals, involving distinct stages that
      probably perform multiple functions for the brain. Before sleep functions can be
      initiated, it is likely that behavioral responsiveness to the outside world needs
      to be reduced, even while the animal is still awake. Recent work in Drosophila
      has uncovered a sleep switch in the dorsal fan-shaped body (dFB) of the fly's
      central brain, but it is not known whether these sleep-promoting neurons also
      govern the acute need to ignore salient stimuli in the environment during sleep
      transitions. We found that optogenetic activation of the sleep switch suppressed
      behavioral responsiveness to mechanical stimuli, even in awake flies, indicating
      a broader role for these neurons in regulating arousal. The dFB-mediated
      suppression mechanism and its associated neural correlates requires innexin6
      expression, suggesting that the acute need to reduce sensory perception when
      flies fall asleep is mediated in part by electrical synapses.

PMID- 30109987
TI  - WSe2/Au vertical Schottky junction photodetector with low dark current and fast
      photoresponse.
AB  - Atomically thin two-dimensional materials including graphene, transition metal
      dichalcogenides, black phosphorus and so forth have been considered as promising
      channel medias for electronic and optoelectronic devices in the past few years.
      However, the poor photoresponse time and the large dark current are the two major
      issues which greatly block their applications. Here, we report a vertical Au-WSe2
      ITO (indium tin oxide) Schottky junction photodetector with a broadband
      photoresponse from 550-950 nm and a stable photovoltaic responsivity of ~0.1 A W
      1. The fast photoresponse of ~50 MUs and low dark current of ~1 pA are achieved
      at the vertical Au-WSe2-ITO photodetector. These results indicate that metal
      contact to a 2D material-based vertical Schottky junction can achieve an
      excellent photoelectric response.

PMID- 30109984
TI  - Optogenetic dissection of mitotic spindle positioning in vivo.
AB  - The position of the mitotic spindle determines the plane of cell cleavage, and
      thereby daughter cell location, size, and content. Spindle positioning is driven
      by dynein-mediated pulling forces exerted on astral microtubules, which requires
      an evolutionarily conserved complex of Galpha?GDP, GPR-1/2Pins/LGN, and LIN
      5Mud/NuMA proteins. To examine individual functions of the complex components, we
      developed a genetic strategy for light-controlled localization of endogenous
      proteins in C. elegans embryos. By replacing Galpha and GPR-1/2 with a light
      inducible membrane anchor, we demonstrate that Galpha?GDP, Galpha?GTP, and GPR
      1/2 are not required for pulling-force generation. In the absence of Galpha and
      GPR-1/2, cortical recruitment of LIN-5, but not dynein itself, induced high
      pulling forces. The light-controlled localization of LIN-5 overruled normal cell
      cycle and polarity regulation and provided experimental control over the spindle
      and cell-cleavage plane. Our results define Galpha?GDP-GPR-1/2Pins/LGN as a
      regulatable membrane anchor, and LIN-5Mud/NuMA as a potent activator of dynein
      dependent spindle-positioning forces.

PMID- 30109986
TI  - Cascaded atrous convolution and spatial pyramid pooling for more accurate tumor
      target segmentation for rectal cancer radiotherapy.
AB  - Convolutional neural networks (CNNs) have become the state-of-the-art method for
      medical segmentation. However, repeated pooling and striding operations reduce
      the feature resolution, causing loss of detailed information. Additionally,
      tumors of different patients are of different sizes. Thus, small tumors may be
      ignored while big tumors may exceed the receptive fields of convolutions. The
      purpose of this study is to further improve the segmentation accuracy using a
      novel CNN (named CAC-SPP) with cascaded atrous convolution (CAC) and a spatial
      pyramid pooling (SPP) module. This work is the first attempt at applying SPP for
      segmentation in radiotherapy. We improved the network based on ResNet-101
      yielding accuracy gains from a greatly increased depth. We added CAC to extract a
      high-resolution feature map while maintaining large receptive fields. We also
      adopted a parallel SPP module with different atrous rates to capture the multi
      scale features. The performance was compared with the widely adopted U-Net and
      ResNet-101 with independent segmentation of rectal tumors for two image sets,
      separately: (1) 70 T2-weighted MR images and (2) 100 planning CT images. The
      results show that the proposed CAC-SPP outperformed the U-Net and ResNet-101 for
      both image sets. The Dice similarity coefficient values of CAC-SPP were 0.78  +/-
      0.08 and 0.85  +/-  0.03, respectively, which were higher than those of U-Net
      (0.70  +/-  0.11 and 0.82  +/-  0.04) and ResNet-101 (0.76  +/-  0.10 and 0.84 
      +/-  0.03). The segmentation speed of CAC-SPP was comparable with ResNet-101, but
      about 36% faster than U-Net. In conclusion, the proposed CAC-SPP, which could
      extract high-resolution features with large receptive fields and capture multi
      scale context yields, improves the accuracy of segmentation performance for
      rectal tumors.

PMID- 30109985
TI  - Single-particle cryo-EM structure of a voltage-activated potassium channel in
      lipid nanodiscs.
AB  - Voltage-activated potassium (Kv) channels open to conduct K+ ions in response to
      membrane depolarization, and subsequently enter non-conducting states through
      distinct mechanisms of inactivation. X-ray structures of detergent-solubilized Kv
      channels appear to have captured an open state even though a non-conducting C
      type inactivated state would predominate in membranes in the absence of a
      transmembrane voltage. However, structures for a voltage-activated ion channel in
      a lipid bilayer environment have not yet been reported. Here we report the
      structure of the Kv1.2-2.1 paddle chimera channel reconstituted into lipid
      nanodiscs using single-particle cryo-electron microscopy. At a resolution of ~3 A
      for the cytosolic domain and ~4 A for the transmembrane domain, the structure
      determined in nanodiscs is similar to the previously determined X-ray structure.
      Our findings show that large differences in structure between detergent and lipid
      bilayer environments are unlikely, and enable us to propose possible structural
      mechanisms for C-type inactivation.

PMID- 30109988
TI  - Synthesis of ZnO nanowires with supercritical carbon dioxide and post heat
      treatment.
AB  - Zinc oxide (ZnO) nanowires are used in applications such as gas sensors and solar
      cells. This work presents a novel synthesis route for ZnO nanowires using
      supercritical carbon dioxide (scCO2) and post heat treatment. The method used
      scCO2 and a precursor solution as reactants to form nanowires on a galvanized
      surface. After the scCO2 treatment, the substrate was heat-treated. The surfaces
      were characterized with SEM, TEM, EDS, FTIR, XRD and optical spectroscopy. The
      FTIR results showed that the surface structure had changed from zinc
      hydroxycarbonate to ZnO during the heat treatment. The nanowires were slightly
      bent due to the heat treatment according to the SEM images. The presence of ZnO
      was further confirmed with XRD. The bandgap of the structure was determined by
      reflectance measurements and showed a value of 3.23 eV. The synthesis method
      presented in this study offers a unique approach into the formation of ZnO
      nanowires in a facile, rapid and environmentally friendly process.

PMID- 30109989
TI  - Dose evaluation of fast synthetic-CT generation using a generative adversarial
      network for general pelvis MR-only radiotherapy.
AB  - To enable magnetic resonance (MR)-only radiotherapy and facilitate modelling of
      radiation attenuation in humans, synthetic CT (sCT) images need to be generated.
      Considering the application of MR-guided radiotherapy and online adaptive
      replanning, sCT generation should occur within minutes. This work aims at
      assessing whether an existing deep learning network can rapidly generate sCT
      images for accurate MR-based dose calculations in the entire pelvis. A study was
      conducted on data of 91 patients with prostate (59), rectal (18) and cervical
      (14) cancer who underwent external beam radiotherapy acquiring both CT and MRI
      for patients' simulation. Dixon reconstructed water, fat and in-phase images
      obtained from a conventional dual gradient-recalled echo sequence were used to
      generate sCT images. A conditional generative adversarial network (cGAN) was
      trained in a paired fashion on 2D transverse slices of 32 prostate cancer
      patients. The trained network was tested on the remaining patients to generate
      sCT images. For 30 patients in the test set, dose recalculations of the clinical
      plan were performed on sCT images. Dose distributions were evaluated comparing
      voxel-based dose differences, gamma and dose-volume histogram (DVH) analysis. The
      sCT generation required 5.6 s and 21 s for a single patient volume on a GPU and
      CPU, respectively. On average, sCT images resulted in a higher dose to the target
      of maximum 0.3%. The average gamma pass rates using the 3%, 3 mm and 2%, 2 mm
      criteria were above 97 and 91%, respectively, for all volumes of interests
      considered. All DVH points calculated on sCT differed less than  +/-2.5% from the
      corresponding points on CT. Results suggest that accurate MR-based dose
      calculation using sCT images generated with a cGAN trained on prostate cancer
      patients is feasible for the entire pelvis. The sCT generation was sufficiently
      fast for integration in an MR-guided radiotherapy workflow.

PMID- 30109990
TI  - Electromagnetic energy harvesting based on HfZrO tunneling junctions.
AB  - HfZrO ferroelectrics with a thickness of 6 nm were grown directly on Si using
      atomic layer deposition, top and bottom metallic electrodes being subsequently
      deposited by electron-beam metallization techniques. Depending on the polarity of
      the +/-10 V poling voltages, the current-voltage dependence of these tunneling
      diodes shows a rectifying behavior for different polarizations, the ON-OFF ratio
      being about 104. Because the currents are at mA level, the HfZrO tunneling diodes
      coupled to an antenna array can harvest electromagnetic energy at 26 GHz (a
      bandwidth designated for internet of things), with a responsivity of 63 V W-1 and
      a NEP of 4 nW/Hz0.5.

PMID- 30109991
TI  - Pre-ejection period, the reason why the electrocardiogram Q-wave is an unreliable
      indicator of pulse wave initialization.
AB  - OBJECTIVE: Pulse wave velocity measurements are an indicator of arterial
      stiffness and possible cardiovascular dysfunction. It is usually calculated by
      measuring the pulse transit time (PTT) over a known distance through the
      arteries. In animal studies, reliable PTT measures can be obtained using two
      pressure catheters. However, such direct, invasive methods are undesirable in
      clinical settings. A less invasive alternative measure of PTT is pulse arrival
      time (PAT), the time between the Q-wave of an electrocardiogram (ECG) and the
      arrival of the foot of the beats pressure waveform at one pressure catheter.
      Since the Q-wave signifies the start of ventricular contraction, PAT includes the
      pre-ejection period (PEP), a time where no blood is ejected. Thus, inter- or
      intra- subject variation in PEP could result in poor correlation between pulse
      arrival time (PAT) and the desired pulse transit time (PTT). APPROACH: This study
      looks at the relationship between PAT and PTT, over a range of common critical
      care therapies and determines the effect of PEP on PAT as a possible surrogate of
      PTT in a critical care environment. The analysis uses data from five porcine
      experiments, where ECG, aortic arch and abdominal aortic pressure were measured
      simultaneously, over a range of induced hemodynamic conditions. RESULTS: The
      resulting correlations of PAT verse PTT varied within pigs and across
      interventions (r 2  =  0.32-0.69), and across pigs (r 2  =  0.05-0.60).
      Variability was due to three main causes. First, the interventions themselves
      effect PEP and PTT differently, second, pig specific response to the
      interventions, and third, inter- and intra- pig variability in PEP, independent
      of PTT. SIGNIFICANCE: The overall analysis shows PAT is an unreliable measure of
      PTT and a poor surrogate under clinical interventions common in a critical care
      setting, due to intra- and inter- subject variability in PEP.

PMID- 30109992
TI  - Brownian dynamics simulations of the ionic current traces for a neutral
      nanoparticle translocating through a nanopore.
AB  - In this work, the ionic current blockades due to the translocation of a neutral
      spherical nanoparticle through a nanopore in a solid state membrane are computed.
      We use a Brownian dynamics approach, in conjunction with a full three-dimensional
      self-consistent solution of the Poisson-Nernst-Planck and Navier-Stockes system
      of equations to describe realistic ionic current response arising due to the
      random motion of a nanoparticle through a nanopore. We find that in addition to
      the usual geometric blockade, the variations of the current along the axis of the
      pore are largely caused by a concentration polarization induced by the presence
      of the translocating nanoparticle in the nanopore while the current changes in
      the radial (perpendicular to the axis) direction occur because of the local build
      up of the ionic charge between the particle and the nanopore surface. By
      performing statistical analysis of the current traces, we also observe that, in
      general, smaller current blockade values correspond to faster translocation
      times, while increased dwell times result in a larger current decrease.

PMID- 30109993
TI  - Comparison of pressure, volume and gas washout characteristics between PCV and
      HFPV in healthy and formalin fixed ex vivo porcine lungs.
AB  - OBJECTIVE: This study employs a recently developed experimental technique for
      comparison of the flow characteristics and the effectiveness of gas washout
      between pressure control ventilation (PCV) and high-frequency percussive
      ventilation (HFPV) in high-compliance and low-compliance ex vivo porcine
      respiratory tracts. APPROACH: The ex vivo porcine lungs are filled with nitrogen
      prior to ventilating with atmospheric gas using either PCV or HFPV to investigate
      the flow characteristics and gas washout characteristics. The study considered
      freshly removed lungs from porcine carcasses that were humanely harvested for
      human consumption. Subsequently, the porcine lungs were exposed externally to
      formalin to simulate low-compliance conditions. The first order models of
      respiratory mechanics were employed to predict the lung compliance and resistance
      in normal and formalin exposed lungs. HFPV was operated in two different modes
      based upon the set pressures, namely HFPV-Low and HFPV-High. The peak pressures
      of HFPV and PCV were matched in HFPV-Low and the peak pressures are increased to
      about 20-30% in the HFPV-High mode. MAIN RESULTS: Both HFPV-Low and HFPV-High
      mode deliver smaller tidal volume (V T) as compared to PCV in high and compliance
      states (about 70% and 40% for healthy and formalin treated lungs, repsectively).
      Although the tidal volume delivered by HFPV-High and HFPV-Low are comparable,
      they reveal a substantial difference in washout time as well as total ventilation
      volumes. In a high compliant lung (healthy lung), HFPV-High washes out the
      nitrogen within the lung more rapidly, whereas HFPV-Low washes out the inert gas
      more slowly as compared to PCV. In a low-compliance lung, HFPV-Low delivers
      similar washout rates as PCV at a much smaller V T and lower mean airway
      pressure. SIGNIFICANCE: The ex vivo study supports the hypothesis that in low
      compliant lungs HFPV provides effective washout with a protective ventilation.

PMID- 30109994
TI  - Size-tunable Ag nanoparticles sensitized porous ZnO nanobelts: controllably
      partial cation-exchange synthesis and selective sensing toward acetic acid.
AB  - Porous ZnO nanobelts sensitized with Ag nanoparticles have been prepared via a
      partial cation-exchange reaction assisted by a thermal oxidation treatment,
      employing ZnSe.0.5N2H4 nanobelts as precursors. After partially exchanged with
      Ag+ cations, the belt-like morphology of the precursors is still preserved.
      Continuously calcined in air, they are in situ transformed into Ag nanoparticles
      sensitized porous ZnO nanobelts. The size of the Ag nanoparticles can be tuned
      through manipulating the amount of exchanging Ag+ cations. Considering the porous
      and belt-like nanostructure, sensing characteristics of ZnO and the catalytic
      activity of Ag nanoparticles, the gas sensing performances of the as-prepared Ag
      nanoparticles sensitized porous ZnO nanobelts have been carefully investigated.
      The results indicate that Ag nanoparticles significantly enhance the sensing
      performances of porous ZnO nanobelts toward typical volatile organic compounds.
      Especially, a good selectivity has been demonstrated toward acetic acid gas with
      a low detection limit less than 1 ppm. Furthermore, they also display a good
      reproducibility with a short response/recovery time due to the thin, uniform and
      porous sensing film, which is fabricated with the assembled technique and in situ
      calcined approach. Finally, their sensing mechanism has been further discussed.

PMID- 30109995
TI  - A key-point based real-time tracking of lung tumor in x-ray image sequence by
      using difference of Gaussians filtering and optical flow.
AB  - In radiation therapy, for accurate radiation dose delivery to a target tumor and
      reduction of the extra exposure of normal tissues, real-time tumor tracking is
      typically an important technique in lung cancer treatment since lung tumors move
      with patients' respiration. To observe a tumor motion in real time, x-ray
      fluoroscopic devices can be employed, and various tracking techniques have been
      proposed to track tumors. However, development of a fast and accurate tracking
      method for clinical use is still a challenging task since the obscured image of
      the tumor can cause decreased tracking accuracy and can result in additional
      processing time for remedying the accuracy. In this study, a new key-point-based
      tumor tracking method, which is sufficiently fast and accurate, is presented.
      Given an x-ray image sequence, the proposed method employs a difference-of
      Gaussians filtering technique to detect key points in the tumor region of the
      first frame which are robust against noise and outliers in the subsequent frames.
      In the subsequent frames, these key points are tracked using a fast optical flow
      technique, and tumor motion is estimated via their movement. To evaluate the
      performance, the proposed method has been tested on several clinical kV and MV x
      ray image sequences. The experimental results showed that the average of the root
      mean square errors of tracking were [Formula: see text] and [Formula: see text]
      for kV and MV x-ray image sequences, respectively. This tracking performance was
      more accurate than previous tracking methods. In addition, the average processing
      times for each frame were [Formula: see text] and [Formula: see text] for kV and
      MV image sequences, respectively, and the proposed method was faster than
      previous methods as well as shorter than frame acquisition interval. Therefore,
      the proposed method has the potential for both highly accurate and fast tumor
      tracking in clinical applications.

PMID- 30109996
TI  - An unsupervised convolutional neural network-based algorithm for deformable image
      registration.
AB  - The purpose of the work is to develop a deep unsupervised learning strategy for
      cone-beam CT (CBCT) to CT deformable image registration (DIR). This technique
      uses a deep convolutional inverse graphics network (DCIGN) based DIR algorithm
      implemented on 2 Nvidia 1080 Ti graphics processing units. The model is comprised
      of an encoding and decoding stage. The fully-convolutional encoding stage learns
      hierarchical features and simultaneously forms an information bottleneck, while
      the decoding stage restores the original dimensionality of the input image.
      Activations from the encoding stage are used as the input channels to a sparse
      DIR algorithm. DCIGN was trained using a distributive learning-based
      convolutional neural network architecture and used 285 head and neck patients to
      train, validate, and test the algorithm. The accuracy of the DCIGN algorithm was
      evaluated on 100 synthetic cases and 12 hold out test patient cases. The results
      indicate that DCIGN performed better than rigid registration, intensity corrected
      Demons, and landmark-guided deformable image registration for all evaluation
      metrics. DCIGN required ~14 h to train, and ~3.5 s to make a prediction on a 512 
      *  512  *  120 voxel image. In conclusion, DCIGN is able to maintain high
      accuracy in the presence of CBCT noise contamination, while simultaneously
      preserving high computational efficiency.

PMID- 30109997
TI  - [Mutations of G38R and D40G cause amyotrophic lateral sclerosis by reducing
      Annexin A11 protein stability].
AB  - OBJECTIVE: To explore the role of the mutations G38R and D40G of Annexin A11
      (ANXA11) in the onset of amyotrophic lateral sclerosis (ALS).? Methods: The
      plasmids expressing ANXA11 wild type protein, ANXA11 G38R protein and ANXA11 D40G
      protein were constructed, respectively. The recombinant plasmids were then
      transfected into HEK293 cells respectively followed by cycloheximide (CHX)
      treatment for 0, 2, 4 and 8 h. The protein expressions of ANXA11 wild type,
      ANXA11 G38R and ANXA11 D40G mutations were determined by Western blot. Gray
      analysis by Image J was performed to compare the half-life of each protein. The
      NSC-34 cell lines constantly expressing ANXA11 wild type protein, ANXA11 G38R
      protein and ANXA11 D40G protein were established. The cells were treated with NP
      40 lysis buffer to examine the protein solubility by Western blot.? Results: Both
      ANXA11 G38R protein and ANXA11 D40G protein showed a shorter half-life than
      ANXA11 wild type protein (P<0.05), while there was no difference between ANXA11
      G38R protein and ANXA11 D40G protein (P>0.05). There was no visible insoluble
      substance in the NP-40 lysates for ANXA11 wild type protein, ANXA11 G38R protein
      and ANXA11 D40G protein.? Conclusion: G38R and D40G mutations reduce the
      stability of ANXA11 protein. G38R and D40G mutations do not alter ANXA11
      solubility.

PMID- 30109998
TI  - [Effects of MnSOD silence on in vitro tumorigenicity in NCI-H446 cells].
AB  - OBJECTIVE: To investigate the effect of manganese superoxide dismutase (MnSOD)
      silence on the in vitro tumorigenicity in human small cell lung cancer NCI-H446
      cells and the underlying mechanisms.? Methods: Sphere formation cells from NCI
      H446 cells were obtained by suspension culture, while the expression of MnSOD and
      urokinase type plasminogen activator (uPAR) was analyzed by Western blot. Silence
      of MnSOD was performed by adenovirus infection in the second passage formation
      cells, and the effect of MnSOD silence on tumorigenicity in NCI-H446 cells was
      evaluated by sphere formation assay and soft-agar colony formation assay, while
      the expression of uPAR was analyzed by Western blot.? Results: Compared with NCI
      H446 cells, the sphere formation rate, colony formation rate, and the expression
      of MnSOD and uPAR were significantly increased in the second passage sphere
      formation cells in NCI-H446 cells (P<0.05). Silence of MnSOD inhibited the sphere
      formation rate, colony formation rate, and the expression level of uPAR in the
      second passage sphere formation cells in NCI-H446 cells.? Conclusion: MnSOD may
      promote tumorigenicity in NCI-H446 cells by up-regulation of uPAR expression in
      vitro.

PMID- 30109999
TI  - [Role of p38MAPK signaling pathway in rats with phantom limb pain].
AB  - OBJECTIVE: To investigate the role of p38MAPK signal pathway in spinal cord and
      dorsal root ganglion (DRG) in rats with phantom limb pain and the effects of
      specific inhibitors.? Methods: Healthy adult male SD rats (n=48) were cut off one
      side of the sciatic under anesthesia to establish a model of phantom limb pain.
      In addition, the healthy rats were taken as a sham group (group S, n=24). The
      animals were scored by observing the action of chewing (0=no chewing, 13=the
      worst chewing) after the operation and were sacrificed on the following day after
      the operation. The successful model of phantom limb pain were randomly divided
      into 2 groups: a phantom limb pain group (group P, n=24) and a phantom limb pain
      plus inhibitor group (group P+I, n=24). SB203580 was given to the rat at 0.8
      mg/kg on every Monday until the rats were sacrificed, the rest of the rats
      received an equal amount of saline. Eight rats from each group were randomly
      taken for the determination of levels of P-p38MAPK in spinal cord and DRG before
      administration and on the 4th, 6th, 8th weekend following the administration,
      respectively.? Results: In the sham group, no animal developed chewing.
      Meanwhile, rats in successful model of phantom limb pain group began chewing from
      the 2nd day after operation with scores at eight to eleven. The chewing scores in
      the P+I group were reduced after the treatment. Compared with group S, P-p38MAPK
      levels were elevated in groups of P and P+I (P<0.05 or P<0.01). Compared with
      group P, P-p38MAPK level was decreased in the group P+I (P<0.05 or P<0.01).?
      Conclusion: P38MAPK signal pathway involves in the development of phantom limb
      pain.

PMID- 30110000
TI  - [Rs17042171 at chromosome 4q25 is associated with atrial fibrillation in the
      Chinese Han population from the central plains].
AB  - OBJECTIVE: To determine the correlations of single nucleotide polymorphisms
      (SNPs) with atrial fibrillation (AF) in the Chinese Han population from the
      central plains.? Methods: A total of 168 hospitalized patients, including 56 AF
      and 112 controls, were recruited in this case-control study. The clinical data
      were obtained from the medical records. All 5 SNPs, rs337711 in KCNN2, rs11264280
      near KCNN3, rs17042171 near PITX2, rs6771157 and rs6795970 in SCN10A, were
      genotyped using amplification refractory mutation system-polymerase chain
      reaction or direct sequencing. The chi2 test was used to compare categorical
      variables and preliminarily examine correlations between the genotype frequencies
      and AF. Subsequently, a logistic regression model was constructed to determine
      the associations between the SNPs and AF based on the above screened results.
      Odds ratios (ORs) and 95% confidence interval (CI) were calculated to assess the
      strength of the correlations. Moreover, we downloaded the genotype data from the
      HapMap Project for linkage disequilibrium analysis of rs17042171.? Results: AF
      patients were likely to be of older age and longer left atrial diameter and had
      more coronary artery disease and higher hypertension compared with the control
      group (P<0.05). Among the 5 SNPs, the frequency distribution of genotype AA for
      rs17042171 was significantly different between the AF and control groups
      (P<0.05). After adjusting for several covariates, there was still a high risk
      ratio in patients with the AA genotype compared with the AC+CC genotype (OR:
      5.591, 95%CI 2.176 to 14.365, P-B<0.008). Similarly, stratification analysis on
      the AA genotype demonstrated significant differences between rs17042171 and
      persistent AF. However, there were not significant correlations between AF and
      the control groups for the other 4 SNPs (P<0.05).? Conclusion: Rs17042171, near
      PITX2 on chromosome 4q25, is associated with AF susceptibility in the Chinese Han
      population from the central plains, suggesting that this SNP can provide a new
      strategy for clinical diagnosis in AF patients.

PMID- 30110001
TI  - [Ablation of paroxysmal supraventricular tachycardia guided by Carto Univu
      electroanatomic mapping system].
AB  - OBJECTIVE: To explore the safety and efficacy for radiofrequency ablation of
      paroxysmal supraventricular tachycardia (PSVT) guided by Carto Univu three
      dimensional mapping system.? Methods: A total of 99 patients with PSVT underwent
      radiofrequency catheter ablation (RFCA) were assigned to a Carto Univu group (51
      patients) and a two-dimensional X-ray group (48 patients) according to the
      mapping method. The operation time, X-ray exposure time, X-ray exposure dose,
      dose area product (DAP), operation success rate and complication rate were
      compared between the two groups.? Results: The Carto Univu group and the two
      dimensional X-ray group were not significant difference in the operation time,
      the X-ray exposure time of placing catheter, the X-ray DAP of placing catheter,
      the number of discharge, the discharge power, and the total discharge time
      (P>0.05). The mapping and ablation time, total exposure time, mapping and
      ablation DAP and total DAP in the Carto Univu group were significantly lower than
      those in the two-dimensional X-ray group (P<0.01). In the right accessory pathway
      cases, the mapping and ablation DAP and the total DAP in the Carto Univu group
      decreased compared with X-ray group (P<0.05), but it decreased more profound
      (P<0.01) in the left accessory pathway cases and the dual atrioventricular nodal
      pathways cases. Seven cases in the Carto Univu group achieved "zero X-ray",
      including 5 cases of the dual atrioventricular nodal pathways and 2 cases of the
      left accessory pathway. The immediate success rate for the two groups was 100%.
      After 3-12 months of follow-up, there was no recurrence in the Carto Univu group
      but 3 suspected recurrences in the two-dimensional X-ray group. In addition, no
      complications occurred in the two groups. ? Conclusion: Carto Univu
      electroanatomic mapping system can guide PSVT safely and effectively during
      radiofrequency ablation and reduce radiation exposure to both doctors and
      patients. It is especially suitable for dual atrioventricular nodal pathways,
      which may even achieve "zero X-ray". Perhaps Carto Univu will be the first choice
      for RFCA of dual atrioventricular nodal pathways.

PMID- 30110003
TI  - [Remineralization of demineralized dentin induced by bioactive glass NovaMin].
AB  - OBJECTIVE: To explore the remineralization effect of bioactive glass NovaMin on
      demineralized dentin specimens, and to study the physical and chemical properties
      of formed structure at dentin surface.? Methods: One mm-thickness coronal dentin
      slices were soaked in ethylene diamine tetraacetic acid (EDTA) for 48 h to
      prepare the completely demineralized dentin specimens and they were divided into
      2 groups: an artificial saliva group (control group) and a NovaMin powder group.
      The specimens were treated with artificial saliva or NovaMin powder for 2 min (2
      times every day), and the interval was 8 hours. Then, the specimens were soaked
      in the remineralization solution. After 7 days, the scanning electron microscope
      (SEM), energy dispersive X-ray (EDX), attenuated total reflectance Fourier
      transform infrared spectroscopy (ATR-FTIR) and X-ray diffraction (XRD) were used
      to detect dentin morphology, the physical and chemical properties of the formed
      structure at dentin surface.? Results: The results of SEM showed that a defined
      surface layer in the NovaMin powder group could be observed in the SEM imaging at
      the 7th day, which completely occluded dentinal tubules; the EDX, ATR-FTIR and
      XRD analysis found that the mineralized layer formed at dentin surface was mainly
      composed of calcium and phosphate elements, which was similar to the
      hydroxyapatite-like crystal. However, there were no materials formed at the
      dentin surface in the control group, and the dentinal tubules were still open.?
      Conclusion: NovaMin can remineralize the demineralized dentin specimens and
      occlude the dentinal tubules in hydroxyapatite-like crystal structure.

PMID- 30110002
TI  - [Development and evaluation of ultrasound contrast agents with AS1411-conjugated
      nanoparticles with liquid core].
AB  - OBJECTIVE: To prepare AS1411 targeted nano-ultrasonic contrast agent with liquid
      core, and to evaluate its ability for ultrasonic contrast enhancement and
      targeting MCF-7 cell in vitro.? Methods: The modified solvent evaporation, self
      synthesized membrane material and perfluorobrominane (PFOB) was used to form nano
      ultrasonic contrast agent with PFOB core (nanoparticles, NP); then N-(3
      dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride and N-hydroxysuccinimide
      (EDC/NHS) catalysis was used to connect AS1411 to the surface of NP to prepare NP
      AS1411. The transmission electron microscopy was chosen to check the morphology
      of NP-AS1411. The size, surface charge, encapsulation efficiency,
      biocompatibility, the contrast grey value and the stability of NP-AS1411 and NP
      were compared. Whether AS411 was attached to the surface of NP was checked by gel
      electrophoresis. Fluorescence microscopy and flow cytometry were performed to
      examine the targeting ability of AS1411.? Results: NP-AS1411 was a shell-nuclear
      structure under the electron microscope. Its size was at (245.4+/-16.5) nm, which
      was larger than that of NP (P=0.05). There was no significant difference in
      surface charge and encapsulation efficiency between NP-AS1411 and NP (P>0.05). In
      the MTT experiment, the cell viability decreased significantly at high
      concentration of NP-AS411 (25 mg/mL) after incubation for 24 h compared with the
      control group (0 mg/mL ) (P<0.05). The contrast gray value of NP-AS1411 was at
      86.1+ 6.7, which was significantly higher than that of deionized water (P<0.05),
      and equivalent to that of NP (P>0.05). The contrast grey value of AS1411-NP was
      80.1+/-9.2 after keeping at room temperature for 24 h, which showed no obviously
      change comparing with that before the treatment (P>0.05). The size of NP
      AS1411didn't change too (P>0.05). The results of gel electrophoresis demonstrated
      that the AS1411 connecting to the surface of NP was the most when the molar ratio
      of NP:AS1411 was at 40:1. Flow cytometry analysis confirmed that NP and NP-AS1411
      were combined with MCF-7 cells separately but the fluorescence produced by the
      combination of NP-AS1411 and MCF-7 was more intense.? Conclusion: The modified
      solvent evaporation and EDC/NHS catalysis could successfully prepare ultrasound
      contrast agents with aptamer-conjugated nanoparticles with liquid core. The
      targeted ultrasonic contrast agents with liquid core possess good ultrasonic
      contrast enhancement ability in vitro, stability and specificity as well.

PMID- 30110004
TI  - [Three-dimensional morphological features of temporomandibular joint in skeletal
      malocclusion Class III patients with different vertical skeletal facial types].
AB  - OBJECTIVE: To investigate three-dimensional morphological features of
      temporomandibular joint in skeletal malocclusion Class III with different
      vertical skeletal facial types.? Methods: A total of 46 adults with skeletal
      malocclusion Class III were enrolled and allocated into a normal-angle, a high
      angle and a low-angle groups. All patients were undergone cone beam computed
      tomography (CBCT). Images of temporomandibular joint were reconstructed and
      analyzed by Invivo 5. Nine measurements relevant to the positions and forms of
      condyle as well as joint spaces were performed.? Results: Significant differences
      were not observed between the 2 sides of each group among skeletal malocclusion
      Class III (P>0.05). Compared with the high-angle and normal-angle patients, the
      low-angle patients had larger superior spaces, bigger gradients of the articular
      tublecle, longer condyle, and larger internal spaces between the condyle and the
      fossa. Compared with the low-angle and normal-angle patients, the high-angle
      patients had smaller condylar antero-posterior diameters.? Conclusion: Class III
      malocclusion patients with different vertical skeletal patterns have different
      positions and forms of condyles, which should be paid attention to in clinic.

PMID- 30110005
TI  - [Clinical features and prognosis for anaplastic large cell lymphoma].
AB  - OBJECTIVE: To determine clinical and pathologic profiles for anaplastic large
      cell lymphoma (ALCL).? Methods: The clinical data of 22 patients with ALCL were
      analyzed retrospectively. Therapentie effect of different treatment strategies on
      ALCL was evaluated.? Results: The median age for these patients was 32(9-70)
      years old and the patients with positive ALK accounted for 68.2% (15/22). All
      patients underwent chemotherapy, including regiments of CHOP (cyclophosphamide,
      doxorubicin, vincristine, prednisone), CHOPE (CHOP plus etoposide) or BEACOP
      (CHOP plus etoposide and bleomycin). Fourteen (63.6%) patients achieved initial
      complete remission (CR) and the CR rate for patients with ALK+ was significantly
      higher than that of patients with ALK- (P<0.05), while the age, gender, stage,
      beta 2-microglobulin (2-MG) level, lactate dehydrogenase (LDH) level, B symptoms
      had no significant effect on the rate of CR (P>0.05). After a median follow-up of
      41 (2-150) months, 12 patients were overall survival, the median progression free
      time was 22.5 (2-150) months, and the age, gender, stage, IPI index, ALK
      expression level, beta 2-MG level, LDH level, and B symptoms had no significant
      effect on the rate of overall survival (P>0.05).? Conclusion: ALK-positive occurs
      mainly in ALCL patients. The chemotherapy is still the main treatment, and CHOPE
      regimen is a better initial treatment scheme because the most patients show good
      prognosis.

PMID- 30110006
TI  - Clinical outcomes after medial temporal lobe epilepsy surgery: Anterior temporal
      lobectomy versus selective amygdalohippocampectomy.
AB  - OBJECTIVE: To compare the anterior temporal lobectomy (ATL) with transsylvian
      selective amygdalohippocampectomy (SeAH) in 72 patients with medial temporal lobe
      epilepsy (MTLE) regarding the seizure control and neuropsychological outcomes.?
      Methods: Clinical data and follow-up data were collected and retrospectively
      analyzed. SeAH and ATL were used in 39 and 33 patients, respectively. All
      eligible patients were followed up at least one year. Wechsler Adult Intelligence
      Scale-Revised and the Wechsler Memory Scale-Revised were used to test the
      patients' neuropsychology before and after the surgery for one year.? Results:
      Fifty-nine patients (81.9%) achieved satisfactory seizure control (62.5% Engel
      Class I and 19.4% Class II). ATL obtained 84.8% satisfactory seizure control (28
      patients), and the success rate was 79.5% (31 patients) for SeAH. There was no
      significant difference in seizure control between SeAH and ATL (P=0.760). The
      postoperative verbal IQ of SeAH group increased significantly in both side
      surgery (P<0.05), while the increase was not significant in the group of ATL of
      both side surgery (P>0.05). Regarding left-side surgery, postoperative verbal
      memory and total memory were increased significantly in the group of SeAH
      (P<0.05), while the increases were not significant in the group of ATL (P>0.05).
      In the right-side surgery, postoperative verbal memory and total memory were
      increased significantly in the two surgery strategy groups (P<0.05), while no
      significant increases were seen in non-verbal memory of the two surgery strategy
      groups (P>0.05).? Conclusion: Microsurgery for the treatment of refractory MTLE
      is successful and safe, and should be encouraged. The seizure outcome is not
      different between ATL and SeAH, while regarding as verbal IQ and verbal memory
      outcomes, SeAH may be superior to ATL in dominant hemisphere surgery.

PMID- 30110007
TI  - [Effect of ulinastatin on perioperative glycocalyx and lung function in patients
      undergoing mitral valve replacement surgery].
AB  - OBJECTIVE: To explore the effect of ulinastatin on perioperative glycocalyx and
      lung function in patients undergoing mitral valve replacement surgery.? Methods:
      Fourty patients, undergoing mitral valve replacement, were randomly allocated
      into a control group and an ulinastatin group, which were administrated 50 mL
      normal saline or 2*104 U/kg ulinastatin at the beginning of cardiopulmonary
      bypass (CPB), respectively. The radical artery blood was collected at 4 time
      points: After induction of anesthesia (T0), at 10 min after the start of CPB
      (T1), 1 h after the end of CPB (T2), and 8 h after operation. The concentration
      of syndecan-1 and TNF-alpha in blood was measured. Moreover, the blood gas
      analysis was preformed and the oxygen index (OI) and difference in alveolar
      arterial oxygen partial pressure (PA-aO2) were calculated at T0, T2, and T3.?
      Results: There were no significant difference between the 2 groups in OI, PA-aO2,
      and the concentration of syndecan-1 and TNF-alpha at T0 (P>0.05). The
      concentration of syndecan-1 and TNF-alpha was significantly increased at T1 and
      T2 in the 2 groups, and reached peak at T2. Compared with the control group, the
      concentration of syndecan-1 and TNF-alpha was decreased in the ulinastatin group
      at T1, T2, and T3 (P<0.05). Compared with T0, OI was lower and PA-aO2 was higher
      at T2 and T3 in both groups, but the 2 indexes were improved in the ulinastatin
      group compared with those in the control group (P<0.05).? Conclusion: Ulinastatin
      can improve the post-operative pulmonary ventilation function in patients with
      mitral valve replacement. The mechanism may be associated with the inhibition of
      TNF-alpha release and the reduction of glycocalyx shedding induced by
      ulinastatin.

PMID- 30110008
TI  - [Effect of temperature for tumescence anesthesia solution on intraoperative and
      postoperative pain of endovenous laser ablation of lower extremity varicose
      vein].
AB  - OBJECTIVE: To compare the effect of cold or room temperature of tumescence
      anesthesia solution on pain perception during and after endovenous laser ablation
      (EVLA) for varicose veins of lower limb.? Methods: A total of 51 patients with
      lower extremity varicose vein were treated by EVLA with tumescence anesthesia
      solution. All patients were used for local anesthesia and randomly divided into 2
      groups according to the temperature of tumescence anesthesia solution: Group A
      (n=26) with room temperature (24 C) of tumescence anesthesia solution and Group B
      (n=25) with cold (4 C) tumescence anesthesia solution. Number rating scale (NRS)
      was recorded immediately after the procedure and postoperative 1, 2, 3 day.
      Patients were asked to register pain scores during the week.? Results: The mean
      linear endovenous energy density (LEED) in the 2 groups was not significantly
      different (P>0.05). The ratio of patients without pain during the operation in
      the Group A was lower than that in the Group B (30.8% vs 64%, P<0.05). On the day
      of operation and postoperative day 1, 2, 3, the average number rating scale (NRS)
      scores in the Group A were greater than those in the Group B (P<0.05).
      Postoperative day 1, only 30.8% of the patients in the Group A resumed daily
      activities, which was lower than that (68% of the patients) in the Group B.?
      Conclusion: In the process of EVLA for varicose veins of lower limb, there is
      less pain during operation and post-operation using cold tumescence anesthesia
      solution comparing room temperature tumescence anesthesia solution.

PMID- 30110009
TI  - [Effects of aroma therapy and music intervention on pain and anxious for breast
      cancer patients in the perioperative period].
AB  - OBJECTIVE: To investigate the effect of the aroma therapy and music intervention
      on anxious and pain for the breast cancer patients in the perioperative period
      and the potential mechanisms.? Methods: A total of 100 breast cancer patients who
      received surgical treatment in the comprehensive hospitals of Hunan province were
      recruited for this study. Patients were assigned randomly into a control group,
      an aroma therapy group, a music intervention group, and a joint-therapy group
      (n=25 per group). The patients in the control group received regular post
      surgical nursery, while the patients from other groups received aroma therapy,
      music intervention, or both in addition to the regular nursery. The scale of
      anxiety and pain were measured. The measurements were carried at three time
      points, namely 30 min before the surgery (T1), 30 min after the recovery period
      of anesthesia (T2), and 4 hours after the removal of anesthesia tubing (T3).
      Repeated ANOVA was used to perform statistic analysis.? Results: The scale of
      pain was significantly increased at the post-operation (T2, T3) compared to pre
      surgery (T1). The therapeutic group showed significant decrease in pain at post
      operation (T3) comparing with the control group (P<0.05). The scale of anxiety
      was the highest at pre-surgery (T1). During anaesthesia recovery, the anxiety of
      patients at post-operation T2 and T3 in the therapeutic groups significantly
      decreased compared with the control group (P<0.05).? Conclusion: Both the aroma
      therapy and the music therapy can decrease the stress-responsive anxiety and pain
      for the breast cancer patients in the perioperative period.

PMID- 30110010
TI  - [Postoperative anxiety and its relationship with life quality in patients with
      Meniere's diseases].
AB  - OBJECTIVE: To investigate the postoperative anxiety and its relationship with
      life quality in patients with Meniere's diseases.? Methods: A total of 68
      patients with Meniere's disease, who received the treatment of endolymphatic sac
      decompression from 2010 to 2016, were enrolled. They finished two scales (the
      self-rating anxiety scale and the quality of life questionnaire for endolymphatic
      sac decompression of Meniere's disease) by snail mail. The patients were divided
      into different groups based on their preoperative course, postoperative follow-up
      time, clinic stage and quality of life after endolymphatic sac decompression
      surgery, and their anxiety was analyzed. In addition, 109 gender and age-matched
      patients with other diseases of otorhinolaryngology served as the control group,
      and their anxiety was also analyzed.? Results: There was no statistical
      difference in the postoperative anxiety among the patients with preoperative
      course for less than 1 year, 1 to 5 years or more than 5 years (all P>0.05).
      There was no statistical difference in the patients with different duration of
      follow-up (P>0.05). There was no statistical difference in the patients with the
      different clinic stages (all P>0.05). There was no statistical difference in the
      patients with the improved life or non-improved life after surgery (P>0.05). The
      degree of the anxiety in the Meniere's group was more severe than that in the
      control group (P<0.01).? Conclusion: It needs to keep in mind that a certain
      degree of postoperative anxiety still keeps in patients with Meniere's disease.

PMID- 30110011
TI  - [Equity of outpatient service utilization for hypertensive patients in
      community].
AB  - OBJECTIVE: To analyze the equity of outpatient service utilization for
      hypertensive patients (HPs) under 3 kinds of social medical insurance, and to
      explore its influential factors.? Methods: A total of 8 670 HPs (aged at 15 years
      old from 28 sub-centers) in 14 provinces were selected. Indirectly standardized
      method and concentration index were used to analyze the equity of outpatient
      utilization in HPs, and decomposition analysis was used to explore the impact
      factors of outpatient treatment among the whole sample population, population
      with urban employees' basic medical insurance (UEBMI), and population with urban
      residents' basic medical insurance (URBMI) and new rural cooperative medical
      systems (NCMS).? Results: The overall concentration index (CI) for the whole
      sample population was 0.2378. After the standardizing "need" variable, horizontal
      inequity (HI) was 0.2360, indicating that the outpatient service of HPs was
      inequity and that the higher economic level, the more outpatient services
      received. The decomposition of overall CI results showed that the positive
      factors for contribution were gross domestic product (GDP) level, retired, UEBMI
      and URBMI, and the negative factors for contribution were NCMS. The CI of UEBMI,
      URBMI and NCMS was 0.2017, 0.1208 and 0.0288, respectively; the HI was 0.1889,
      0.1215 and 0.0219, respectively. The inequity in UEBMI is the most serious,
      followed by NRCMS and URBMI. The economic level was the main factor that caused
      inequity in the outpatient services utilization in three social medical
      insurance. In addition to the economic level, a common positive factor for the
      contribution to UEBMI and URBMI was district of residence, and the age was the
      positive factor to UEBMI as well.? Conclusion: There are different levels of
      inequity in the HPs covered by 3 kinds of social medical insurance, and the
      inequity of UEBMI is the highest one among 3 kinds social medical insurance. The
      economic level is the main factor that affects the equity of outpatient in the
      HPs under 3 kinds of social medical insurance.

PMID- 30110012
TI  - [Construction of the competency model for junior caregivers for the elderly based
      on the combination of medical and endowment model].
AB  - OBJECTIVE: To construct a competency model for junior caregivers for the elderly
      and to provide a reference for the selection, evaluation and training for the
      junior caregivers for the elderly.? Methods: Firstly, we drafted the primary
      competency model for junior caregivers for the elderly through literature review.
      Then, we used Delphi method to carry out 2 rounds of questionnaire survey for 20
      experts to optimize the indicators for primary model. The weight of each
      indicator is determined by analytic hierarchy process (AHP) and expert sequencing
      method.? Results: The effective recovery rates of the two-round questionnaire
      were 87% and 100%, respectively. The expert authority coefficient was 0.70-0.93,
      and the average authority coefficient was 0.80. The final version of the
      competency model for junior caregivers for the elderly included 4 first-grade
      indexes, 11 second-grade indexes and 37 third-grade indexes.? Conclusion: The
      competency model for the junior caregivers for the elderly is reliable and can be
      used as the reference standard for the selection, evaluation and training for the
      junior caregivers for the elderly.

PMID- 30110013
TI  - [Research progress in PRAS40].
AB  - Prolin-rich Akt substrate of 40 kD (PRAS40) is firstly identified as a partner of
      14-3-3 protein and a substrate of Akt kinase by Roth et al in 2003. Accumulated
      evidence shows that PRAS40 is mainly activated by phosphorylate modification at
      different sites. PRAS40 may be involved in various of signaling pathways, such as
      mammalian target of rapamycin complex 1 (mTORC1), protein kinase B (Akt), NF
      kappaB and ribosomal protein L11 (RPL11) etc, which can regulate cell
      proliferation, senescence, autophagy, apoptosis and exosome secretion.

PMID- 30110014
TI  - [Current status for animal models of intensive care unit acquired muscle
      weakness].
AB  - Intensive care unit acquired muscle weakness (ICU-AW) is a neuromuscular
      complication secondary to severe illness. The essence for this disease is
      skeletal muscle dysfunction. With the development of medical technology, the
      survival rate for severe patients has been significantly improved. The long term
      complications for the severe patients with ICU-AW are getting more and more
      common, and they seriously affect the quality of life and prognosis of patients.
      However, the current treatment is ineffective. Establishment of ICU-AW animal
      model is an important way to study the pathogenesis and intervention targets for
      this disease. There are many risk factors for this disease, and the principles
      for ICU-AW animal models are not the same at home and abroad, and the methods of
      preparation are different. The choice of a reasonable animal model is important
      for the reliability of the results.

PMID- 30110015
TI  - Erratum.

PMID- 30110016
TI  - Survival outcomes in patients with non-small-cell lung cancer treated with
      erlotinib.
AB  - Erlotinib is used to treat non-small-cell lung cancer (NSCLC). Erlotinib was
      subsidized on the Pharmaceutical Benefits Schedule in Australia for the treatment
      of advanced stage (IIIB or IV) NSCLC (August 2008). In the pivotal trial
      supporting initial subsidy, erlotinib increased overall survival (OS) by 2 months
      compared with placebo (adjusted hazard ratio, 0.70; 95% confidence interval: 0.58
      0.85). We examined the effectiveness of erlotinib in a 'real-world' setting by
      measuring survival outcomes in NSCLC patients treated in two tertiary
      metropolitan public hospitals in Queensland. We extracted data from the
      electronic oncology prescribing system (CHARM) for NSCLC patients prescribed
      erlotinib (1 September 2009 to 1 February 2015). Survival estimates and analyses
      were generated using Kaplan-Meier curves. 134 patients received at least one dose
      of erlotinib during the study period. At the date of data extraction 113 patients
      had died. The median patient age was 64 years and 55% were men. The median
      duration of treatment was 2.0 months. The median OS was 5.8 months. The median
      progression-free survival (time from start of erlotinib to disease progression or
      death from any cause) was 3.6 months. The use of erlotinib in the two Queensland
      sites was consistent with the pivotal trial used to support subsidy. The median
      OS was somewhat less than the trial (5.8 vs. 6.7 months), which could be because
      of the hospital cohort including frailer patients who were unsuitable for
      parenteral chemotherapy, and the mixed epidermal growth factor receptor mutation
      status of the hospital cohort.

PMID- 30110017
TI  - Promising effects of eribulin for cystic lung metastases of epithelioid sarcoma:
      a case report.
AB  - Epithelioid sarcoma (ES) is a rare and aggressive type of soft tissue sarcoma
      with resistance to systemic chemotherapy. Therefore, new treatment options are
      required for patients with advanced ES. Eribulin is a novel potential treatment
      option for patients with inoperative sarcoma. We herein report a case of a 27
      year-old Japanese man with cystic lung metastases from an ES in the left forearm,
      resulting in long-term stable disease. A solid, metastatic sarcomatous nodule
      appeared in the right lung, as shown by computed tomography, within the first 2
      months after surgery. After the lung metastasis was detected, he underwent a
      total of 37 cycles of chemotherapy in six regimens. However, multiple cystic lung
      metastases had progressed in segments S6 and S9/10; hence, eribulin treatment was
      initiated. After two courses of eribulin, the excess fluid density material in
      the cystic metastases was completely absorbed, and an additional four courses of
      treatment resulted in shrinkage of the cystic metastases. These effects lasted
      for 13 months without severe adverse effects. Cystic lung metastases are an
      extremely rare consequence of soft tissue sarcoma, and eribulin is one of the
      most promising options for the treatment of advanced ES.

PMID- 30110018
TI  - Use of pertuzumab and trastuzumab during pregnancy.
AB  - Trastuzumab and pertuzumab are monoclonal antibodies used for the treatment of
      breast cancer. Until now, there have been no reports on the use of pertuzumab
      during pregnancy and on its potential effects on the fetus. Herein, we present a
      breast cancer patient who received trastuzumab and pertuzumab treatment during
      the first 20 weeks of pregnancy. This 22-year-old patient initially diagnosed
      with invasive ductal carcinoma of the breast was found to be negative for
      estrogen receptor and progesterone receptor and positive for human epidermal
      growth factor receptor in the immunohistochemical examination. At the time of
      diagnosis, she had metastatic lesions and a protocol of docetaxel, trastuzumab,
      pertuzumab, q21, and zolendronic acid 4 mg every month was started. Following six
      courses of therapy, she had near-complete response, and, after administration of
      the same course of treatment for two additional cycles, treatment with pertuzumab
      plus trastuzumab was continued. While she was being followed-up with remission, a
      20-week pregnancy was detected. A fetal ultrasound examination showed
      oligohydramnios and right renal agenesis. Treatment was stopped, and the fetus
      was monitored. After 7 weeks of follow-up, fetal growth retardation and
      anhydramnios were detected. The pregnancy was terminated. Fetal autopsy showed no
      urinary system pathology, but macroscopic and microscopic hyperplasia of the
      right adrenal gland was identified. Concomitant use of pertuzumab and trastuzumab
      during pregnancy may be associated with an unresolved oligohydramnios and/or
      anhydramnios risk. Extreme caution should be used when these monoclonal
      antibodies are administered during pregnancy.

PMID- 30110019
TI  - Adverse Effects of the Medicare PSI-90 Hospital Penalty System on Revenue-Neutral
      Hospital-Acquired Conditions.
AB  - OBJECTIVE: Health systems are grappling with improving the quality and safety of
      health care. By setting clear expectations, there is an opportunity to configure
      care models to decrease the risk of adverse events and promote the quality of
      care. The US Centers for Medicare and Medicaid Services have used Patient Safety
      Indicator 90 (PSI90), a composite rate of hospital-acquired conditions (HACs), to
      adjust payments and score hospitals on quality since 2015. However, PSI90 may be
      associated with adverse prioritization for preventing some conditions over
      others.Our objective was to evaluate the time-dependent rates of HACs between
      2013 and 2016 to assess the association of funding models on adverse events,
      particularly pressure injury. METHODS: We analyzed a retrospective observational
      cohort of patients hospitalized in US Academic Medical Centers observed by the
      Vizient CDB/RM pre-post PSI90 implementation. Changes in HAC component rates of
      PSI90 between 2013 and 2016 were measured longitudinally using mixed-effects
      negative binomial regression modeling. RESULTS: Regardless of whether the
      composite measure of patient outcomes was PSI90 or all HACs, in general, there
      was significant decrease after PSI90 was implemented, reflecting an association
      between PSI90 and CMS reimbursement policy. However, pressure injury rates
      increased by 29.4% (SE = 0.08; P < 0.05) during this time frame, the only HAC
      observed to increase related to PSI90. CONCLUSIONS: Patient safety in hospitals
      will only thoroughly improve when hospitals are fully incentivized to practice
      prevention of all HACs rather than work around the harms that result from failed
      prevention efforts.This is an open-access article distributed under the terms of
      the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY
      NC-ND), where it is permissible to download and share the work provided it is
      properly cited. The work cannot be changed in any way or used commercially
      without permission from the journal.

PMID- 30110020
TI  - What Can Apologies in the Electronic Health Record Tell Us About Health Care
      Quality, Processes, and Safety?
AB  - INTRODUCTION: Apologizing to patients is an encouraged practice, yet little is
      known about how and why providers apologize and what insights apologies could
      provide in improving quality and safety. OBJECTIVE: The aim of the study was to
      determine whether provider apologies in the electronic health record could
      identify patient safety concerns and opportunities for improvement. METHODS:
      After performing a free-text search, we randomly selected 100 clinical notes from
      1685 available containing terminology related to apology. We categorized the
      reason for apology, presence and classification of medical error, level of
      patient harm, and practice improvement opportunities. We compared patient events
      discovered from apologies in the medical record to standard patient incident
      report logs. RESULTS: Of 100 randomly selected apologies, 37 were related to a
      delay in care, 14 to misunderstanding, 11 to access to care, and 8 to information
      technology. For apologies related to delay, the median delay was 6 days (mean =
      8.9, range = 0-41). Twenty-four (65%) of the 37 delays were related to diagnostic
      testing.Medical errors were associated with 46 (46%) of the 100 apologies. Sixty
      four (64%) of the 100 apologies were associated with actionable opportunities for
      improvement. These opportunities were classified into 37 discrete issues across 8
      broad categories. When apology review was compared with standard incident report
      logs, 27 (73%) of the 37 discrete issues identified by patient apology review
      were not found in incident reporting; both methods identified similar rates of
      patient harm. CONCLUSIONS: Review of apologies in the electronic health record
      can identify patient safety concerns and improvement opportunities not apparent
      through standard incident reporting.This is an open-access article distributed
      under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives
      License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work
      provided it is properly cited. The work cannot be changed in any way or used
      commercially without permission from the journal.

PMID- 30110021
TI  - Erratum.

PMID- 30110022
TI  - Erratum.

PMID- 30110023
TI  - Erratum.

PMID- 30110024
TI  - Erratum.

PMID- 30110026
TI  - Efficient and regioselective synthesis of gamma-lactone glycosides through a
      novel debenzylative cyclization reaction.
AB  - An efficient and regioselective approach for the construction of synthetically
      important gamma-lactone glycosides is reported from unprotected aldoses through a
      new debenzylative lactonization (DBL) reaction. The scope and limitations of this
      DBL reaction are described starting from a series of commercially available
      hexoses (l-fucose, d-galactose, d-glucose) and pentoses (d-arabinose, d-ribose, d
      lyxose, d-xylose) to afford the corresponding gamma-lactones in good yields and
      without concomitant delta-lactone formation.

PMID- 30110025
TI  - Enzyme-triggered self-assembly of gold nanoparticles for enhanced retention
      effects and photothermal therapy of prostate cancer.
AB  - A peptide-modified gold nanoparticle was developed for tumour-targeted therapy.
      Triggered by alkaline phosphatase, the CREKA-YPFFK(Nph) peptide can self-assemble
      and further result in accumulation of gold nanoparticles in tumour cells. The
      large-sized gold nanoparticle aggregates cannot escape from the tumour tissue,
      therefore realizing the goal of tumour-specific targeting, enhanced retention and
      photothermal effects.

PMID- 30110027
TI  - Improved model for the refractive index: application to potential components of
      ambient aerosol.
AB  - Understanding the impact of atmospheric aerosols on the global radiative balance
      requires knowing the refractive index (RI) of their components. Currently
      available methods to estimate this property from molecular structure are mostly
      empirical and exhibit significant errors (>10%). This work reports a more
      physically sound model leading to predictions within +/-5% from experiment. The
      root mean square relative error is <1% for general organic compounds, and <2% for
      oxygen-rich compounds of special interest in aerosol chemistry. In this approach,
      the RI is obtained from the Lorentz-Lorenz equation. The molar volume and
      polarizability required as input are obtained from the addition of a so-called
      geometrical fragment (GF) associated with every non-hydrogen atom in the
      molecule. The value of this GF method to the study of ambient aerosol is
      demonstrated through extensive validation and application to compounds that may
      be present in aerosol droplets. In so doing, insight is provided into the origin
      of significant errors previously noted using earlier methods. Moreover, it is
      demonstrated that reference values of the refractive index reported in widely
      used compilations should be considered with caution. Finally, a Python script is
      provided as supplementary information for easy use of the present model to
      estimate molar volume and refractive index for any molecule.

PMID- 30110028
TI  - State-of-the-art computation of the rotational and IR spectra of the methyl
      cyclopropyl cation: hints on its detection in space.
AB  - Recent measurements by the Cassini Ion Neutral Mass Spectrometer demonstrated the
      presence of numerous carbocations in Titan's upper atmosphere. In [Ali et al.,
      Planet. Space Sci., 2013, 87, 96], an analysis of these measurements revealed the
      formation of the three-membered cyclopropenyl cation and its methyl derivatives.
      As a starting point of a future coordinated effort of laboratory experiments,
      quantum-chemical calculations, and astronomical observations, in the present work
      the molecular structure and spectroscopic properties of the methyl-cyclopropenyl
      cation have been investigated by means of state-of-the-art computational
      approaches in order to simulate its rotational and infrared spectra. Rotational
      parameters have been predicted with an expected accuracy better than 0.1% for
      rotational constants and on the order of 1-2% for centrifugal-distortion terms.
      As for the infrared spectrum, despite the challenge of a large amplitude motion,
      fundamental transitions have been computed to a good accuracy, i.e., the
      uncertainties are expected to be smaller than 5-10 wavenumbers.

PMID- 30110032
TI  - Harnessing magnetic dipole resonance in novel dielectric nanomaterials.
AB  - Photonic manipulation with plasmonic materials is typically associated with high
      ohmic losses, which has triggered interest in alternative strategies based on low
      loss dielectric materials. Here we describe a novel dielectric nanomaterial
      capable of supporting strong Mie resonances from the visible to IR regimes. The
      fundamental block of this metamaterial is based on nanopillars in a core-shell
      configuration, with a large refractive index (RI) contrast between the (low RI)
      core and the (high RI) shell. The material showed strongly tunable optical
      resonances that varied from visible to near and mid IR as a function of shell
      thickness, core diameter and inter-pillar spacing. The numerical simulations,
      which are in good agreement with the experimental results, suggest the optical
      response to be dominated by magnetic dipole resonances. This versatile material
      platform is CMOS compatible, can be fabricated in a scalable manner as thin
      films, can act as strong scatterers in colloidal suspensions and thereby can
      provide several promising technological opportunities in nanophotonics.

PMID- 30110033
TI  - Biotransformation of organic selenium compounds in budding yeast, Saccharomyces
      cerevisiae.
AB  - Selenium (Se) is not essential for yeast growth, but it has a metabolic capacity
      to transform inorganic Se species to organic Se compounds such as
      selenomethionine (SeMet). Although the metabolism of inorganic Se species has
      been well discussed, there are no studies revealing how organic Se compounds are
      metabolized in yeast. The aim of this study was to show the specific metabolic
      pathway of organic Se species in yeast. We performed the speciation analysis of
      selenometabolites in budding yeast, Saccharomyces cerevisiae, exposed to
      selenometabolites produced by animals, plants, and microorganisms, such as methyl
      2-acetamido-2-deoxy-1-seleno-beta-d-galactopyranoside (SeSug1, selenosugar 1),
      methyl-2-acetamido-2-deoxy-1-seleno-beta-d-glucopyranoside (SeSug2, selenosugar
      2), trimethylselenonium ions (TMSe), Se-methylselenocysteine (MeSeCys), and
      SeMet. Four selenometabolites, SeSug1, SeSug2, SeMet, and MeSeCys, were commonly
      metabolized into SeMet in yeast. Yeast was able to incorporate TMSe but could not
      metabolize it. Since MeSeCys and selenosugars are the major selenometabolites in
      plants and animals, respectively, yeast is useful for recovering Se as SeMet from
      the selenometabolites produced by other organisms in the ecosystem.

PMID- 30110034
TI  - Microfluidic-based vascularized microphysiological systems.
AB  - Microphysiological systems have emerged in the last decade to provide an
      alternative to in vivo models in basic science and pharmaceutical research. In
      the field of vascular biology, in particular, there has been a lack of a suitable
      in vitro model exhibiting a three-dimensional structure and the physiological
      function of vasculature integrated with organ-on-a-chip models. The rapid
      development of organ-on-a-chip technology is well positioned to fulfill unmet
      needs. Recently, functional integration of vasculature with diverse
      microphysiological systems has been increasing. This recent trend corresponds to
      emerging research interest in how the vascular system contributes to various
      physiological and pathological conditions. This innovative platform has undergone
      significant development, but adoption of this technology by end-users and
      researchers in biology is still a work in progress. Therefore, it is critical to
      focus on simplification and standardization to promote the distribution and
      acceptance of this technology by the end-users. In this review, we will introduce
      the latest developments in vascularized microphysiological systems and summarize
      their outlook in basic research and drug screening applications.

PMID- 30110037
TI  - Divergent synthesis of new alpha-glucosidase inhibitors obtained through a vinyl
      Grignard-mediated carbocyclisation.
AB  - Four new alpha-glucosidase inhibitors have been synthesised through 5-8 synthetic
      steps from a common synthetic intermediate obtained through a recently developed
      carbocyclisation. The compounds were designed as hybrids of the known glucosidase
      inhibitors valienamine, voglibose and miglitol. All four compounds showed
      activity against rat intestinal sucrase with the most potent inhibitor acting at
      low micromolar concentration. The newly synthesised compounds were not as potent
      as miglitol against sucrase but showed greater selectivity towards the tested
      glycosidases. The most potent inhibitors were docked into a homology model built
      for this study of rat intestinal sucrase explaining the difference in potency
      between two diastereoisomers with varying orientation of a secondary amine.

PMID- 30110039
TI  - The New Impact Factor of the Arquivos Brasileiros de Cardiologia (ABC Cardiol),
      1.318: An Achievement of the SBC for Our Scientific Community.

PMID- 30110040
TI  - Executive Summary - Guidelines for Mechanical Circulatory Support of the
      Brazilian Society of Cardiology.

PMID- 30110041
TI  - Cohort of Patients Referred for Brugada Syndrome Investigation in an
      Electrophysiology Service - 19-Year Registry.

PMID- 30110042
TI  - The Economic Burden of Heart Conditions in Brazil.
AB  - BACKGROUND: Heart conditions impose physical, social, financial and health
      related quality of life limitations on individuals in Brazil. OBJECTIVES: This
      study assessed the economic burden of four main heart conditions in Brazil:
      hypertension, heart failure, myocardial infarction, and atrial fibrillation. In
      addition, the cost-effectiveness of telemedicine and structured telephone support
      for the management of heart failure was assessed. METHODS: A standard cost of
      illness framework was used to assess the costs associated with the four
      conditions in 2015. The analysis assessed the prevalence of the four conditions
      and, in the case of myocardial infarction, also its incidence. It further
      assessed the conditions' associated expenditures on healthcare treatment,
      productivity losses from reduced employment, costs of providing formal and
      informal care, and lost wellbeing. The analysis was informed by a targeted
      literature review, data scan and modelling. All inputs and methods were validated
      by consulting 15 clinicians and other stakeholders in Brazil. The cost
      effectiveness analysis was based on a meta-analysis and economic evaluation of
      post-discharge programs in patients with heart failure, assessed from the
      perspective of the Brazilian Unified Healthcare System (Sistema Unico de Saude).
      RESULTS: Myocardial infarction imposes the greatest financial cost (22.4 billion
      reais/6.9 billion USD), followed by heart failure (22.1 billion reais/6.8 billion
      USD), hypertension (8 billion reais/2.5 billion USD) and, finally, atrial
      fibrillation (3.9 billion reais/1.2 billion USD). Telemedicine and structured
      telephone support are cost-effective interventions for achieving improvements in
      the management of heart failure. CONCLUSIONS: Heart conditions impose substantial
      loss of wellbeing and financial costs in Brazil and should be a public health
      priority.

PMID- 30110043
TI  - Economic Burden of Cardiovascular Diseases in Brazil: Are Telemedicine and
      Structured Telephone Support the Solution?

PMID- 30110044
TI  - Adropin and Irisin in Patients with Cardiac Cachexia.

PMID- 30110045
TI  - Genetic Risk in Coronary Artery Disease.

PMID- 30110047
TI  - Heart Rate Variability in Coexisting Diabetes and Hypertension.

PMID- 30110046
TI  - Effects of Coexistence Hypertension and Type II Diabetes on Heart Rate
      Variability and Cardiorespiratory Fitness.
AB  - BACKGROUND: Type 2 diabetes Mellitus (T2DM) is associated with cardiac autonomic
      dysfunction, which is an independent predictor of mortality in chronic diseases.
      However, whether the coexistence of systemic arterial hypertension (HTN) with
      DMT2 alters cardiac autonomic modulation remains unknown. OBJECTIVE: To evaluate
      the influence of HTN on cardiac autonomic modulation and cardiorespiratory
      fitness in subjects with DMT2. METHODS: 60 patients of both genders were
      evaluated and allocated to two groups: DMT2 patients (n = 32; 51 +/- 7.5 years
      old) and DMT2 + HTN patients (n = 28; 51 +/- 6.9 years old). RR intervals were
      obtained during rest in supine position. Linear and nonlinear indices of heart
      rate variability (HRV) were computed using Kubios HRV software. Pulmonary gas
      exchange was measured breath-by-breath, using a portable telemetric system during
      maximal incremental exercise testing on a cycle ergometer. Statistical analysis
      included Shapiro-Wilk test followed by Student's t Test, Pearson correlation and
      linear regression. RESULTS: We found that patients in the DMT2+HTN group showed
      lower values of mean RR intervals (801.1 vs 871.5 ms), Shannon entropy (3 vs 3.2)
      and fractal dimension SD 1 (9.5 vs 14.5), when contrasted with patients in the
      DMT2 group. Negative correlations were found between some HRV nonlinear indices
      and exercise capacity indices. CONCLUSION: HTN negatively affects the cardiac
      autonomic function in diabetic patients, who are already prone to develop
      autonomic dysfunction. Strategies are need to improve cardiac autonomic
      functionality in this population.

PMID- 30110048
TI  - Right Ventricular Dysfunction in Lupus Patients With Pulmonary Hypertension.

PMID- 30110049
TI  - Carotid Sinus Massage in Syncope Evaluation: A Nonspecific and Dubious Diagnostic
      Method.
AB  - BACKGROUND: Carotid sinus hypersensitivity (CSH) is a frequent finding in the
      evaluation of syncope. However, its significance in the clinical setting is still
      dubious. A new criterion was proposed by Solari et al. with a symptomatic
      systolic blood pressure (SBP) cut-off value of <= 85 mmHg to refine the
      vasodepressor (VD) response diagnosis. OBJECTIVE: To determine and compare the
      response to carotid sinus massage (CSM) in patients with and without syncope
      according to standard and proposed criteria. METHODS: CSM was performed in 99
      patients with and 66 patients without syncope. CSH was defined as
      cardioinhibitory (CI) for asystole >= 3 seconds, or as VD for SBP decrease >= 50
      mmHg. RESULTS: No differences in the hemodynamic responses were observed during
      CSM between the groups, with 24.2% and 25.8% CI, and 8.1% and 13.6% VD in the
      symptomatic and asymptomatic groups, respectively (p = 0.466). A p value < 0.050
      was considered statistically significant. During the maneuvers, 45 (45.45%) and
      34 (51.5%) patients in the symptomatic and asymptomatic groups achieved SBP below
      <= 85 mmHg. Symptoms were reported especially in those patients in whom CSM
      caused a SBP decrease to below 90 mmHg and/or asystole > 2.5 seconds, regardless
      of the pattern of response or the presence of previous syncope. CONCLUSION: The
      response to CSM in patients with and without syncope was similar; therefore, CSH
      may be an unspecific condition. Clinical correlation and other methods of
      evaluation, such as long-lasting ECG monitoring, may be necessary to confirm CSH
      as the cause of syncope.

PMID- 30110050
TI  - Carotid Sinus Massage in Syncope Evaluation: A Nonspecific and Dubious Diagnostic
      Method.

PMID- 30110051
TI  - How to Evaluate Cardiac Autonomic Modulation.

PMID- 30110052
TI  - Indications of PCSK9 Inhibitors for Patients at High and Very High Cardiovascular
      Risk.

PMID- 30110053
TI  - Case 4/2018 - Important Mitral Valve Regurgitation Caused by Hammock Mitral Valve
      in 8 Year-Old Girl.

PMID- 30110054
TI  - Left Ventricular Assist Device as a Bridge to Candidacy in End-stage Chagas
      Cardiomyopathy.

PMID- 30110055
TI  - Challenging Evaluation of Aortic Regurgitation: More Than a Quadricuspid Valve.

PMID- 30110056
TI  - Challenges For Percutaneous Left Atrial Appendage Closure: Imaging And Residual
      FlowReply.

PMID- 30110057
TI  - Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB
      protein expressions in rats with severe acute pancreatitis1.
AB  - PURPOSE: To investigate the effects of baicalin on inflammatory reaction,
      oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF
      kappaB) protein expressions in severe acute pancreatitis (SAP) rats. METHODS:
      Sixty rats were divided into sham operation, model, and low-, medium- and high
      dose baicalin group. SAP model was established in later 4 groups. The later 3
      groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection,
      respectively. At 12 h, the serum SAP related indexes and inflammatory factors,
      peripheral blood CD3 and gammadeltaT cell percentages, wet/dry ratio and pancreas
      ascites volume, oxidative stress indexes and PKD1 and NF-kappaB protein
      expressions in pancreatic tissue were determined. RESULTS: Compared with model
      group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum
      amylase level, phospholipase A2 activity, TNF-alpha, IL-1 and IL-6 levels, and
      pancreatic malondialdehyde level and PKD1 and NF-kappaB protein expression were
      significantly decreased (P < 0.05), and peripheral blood CD3 and gammadeltaT cell
      percentages and pancreatic superoxide dismutase and glutathione peroxidase levels
      were significantly increased (P < 0.05). CONCLUSION: Baicalin can resist the
      inflammatory reaction and oxidative stress, and down-regulate protein kinase D1
      and nuclear factor-kappa B protein expressions, thus exerting the protective
      effects on severe acute pancreatitis in rats.

PMID- 30110058
TI  - Rectal application of argan oil improves healing of colorectal anastomosis in
      rats1.
AB  - PURPOSE: To investigate the possible effects of argan oil on the healing of
      colorectal anastomoses. METHODS: n Group 1 (sham), laparotomy was performed and
      the colon was mobilized. In the control (Group 2) and argan oil (Group 3) groups,
      colonic resection and anastomosis were applied. To the control and sham groups, 2
      mL of 0.9% NaCl was administred rectally, and in the argan oil group, 2 mL/day
      argan oil was applied rectally for 7 days. RESULTS: The mean bursting pressures
      of the argan oil and sham groups were significantly higher than the values in the
      control group. A significant difference was determined between the tissue
      hydroxyproline and prolidase levels of control group and other groups.
      Histopathologically, argan oil showed significant beneficial effects on colonic
      wound healing. In the argan oil and sham groups, the tissue malondialdehyde and
      fluorescent oxidation product levels were found to be lower and total sulfhydryl
      levels were higher than the control group. CONCLUSIONS: The rectally administered
      argan oil was observed to have significantly ameliorated wound healing parameters
      and exerted a significant antioxidant effect. This is the first study in the
      literature about the beneficial effects of argan oil on colorectal anastomoses.

PMID- 30110059
TI  - The effects of inhaled NO on plasma vasoactive factor and CTnI level in rabbits
      with acute massive pulmonary embolism1.
AB  - PURPOSE: To investigate changes in the plasma concentrations of cardiac troponin
      I (CTnI), thromboxane A2 (TXA2), prostaglandin I2 (PGI2) and endothelin-1 (ET-1)
      in rabbits with massive pulmonary embolism (AMPE) and the impact of nitric oxide
      inhalation (NOI) on these indices. METHODS: A total of 30 Japanese rabbits were
      used to construct an MPE model and were divided into 3 groups equally (n=10),
      including an EXP group (undergoing modeling alone), an NOI group (receiving NOI 2
      h post-modeling) and a CON group (receiving intravenous physiological saline).
      RESULTS: In the model group, plasma concentration of CTnI peaked at 16 h
      following modeling (0.46+/-0.10 ug/ml) and significantly decreased following NOI.
      Plasma levels of TXB2, PGI2 and ET-1 peaked at 12, 16 and 8 h following modeling,
      respectively, and significantly decreased at different time points (0, 2, 4, 8,
      12, 16, 20 and 24 h) following NOI. A significant correlation was observed
      between the peak plasma CTnI concentration and peak TXB2, 6-keto prostaglandin
      F1alpha and ET-1 concentrations in the model and NOI groups. CONCLUSION:
      Increases in plasma TXA2, PGI2 and ET-1 levels causes myocardial damage in a
      rabbit model of AMPE; however, NOI effectively down regulates the plasma
      concentration of these molecules to produce a myocardial-protective effect.

PMID- 30110060
TI  - Cardioprotective effect of preconditioning is more efficient than
      postconditioning in rats submitted to cardiac ischemia and reperfusion1.
AB  - PURPOSE: To investigate the cardioprotective effects of ischemic preconditioning
      (preIC) and postconditioning (postIC) in animal model of cardiac
      ischemia/reperfusion. METHODS: Adult rats were submitted to protocol of cardiac
      ischemia/reperfusion (I/R) and randomized into three experimental groups: cardiac
      I/R (n=33), preCI + cardiac I/R (n=7) and postCI + cardiac I/R (n=8). After this
      I/R protocol, the incidence of ventricular arrhythmia (VA), atrioventricular
      block (AVB) and lethality (LET) was evaluated using the electrocardiogram (ECG)
      analysis. RESULTS: After reestablishment of coronary blood flow, we observed
      variations of the ECG trace with increased incidence of ventricular arrhythmia
      (VA) (85%), atrioventricular block (AVB) (79%), and increase of lethality (70%)
      in cardiac I/R group. The comparison between I/R + preIC group with I/R group
      demonstrated significant reduction in VA incidence to 28%, AVB to 0% and
      lethality to 14%. The comparison of I/R + postIC group with I/R group was
      observed significance reduction in AVB incidence to 25% and lethality to 25%.
      CONCLUSION: The preconditioning strategies produce cardioprotection more
      efficient that postconditioning against myocardial dysfunctions and lethality by
      cardiac ischemia and reperfusion.

PMID- 30110062
TI  - Gastroprotective and antioxidant effects of Eremurus spectabilis Bieb. methanol
      extract and its isolated component isoorientin on indomethacin induced gastric
      ulcers in rats1.
AB  - PURPOSE: To investigate the gastroprotective effect of methanol extract of E.
      spectabilis and its major component isoorientin. METHODS: Effects of isoorientin
      and methanol extract of E. spectabilis were investigated in indomethacin-induced
      gastric damage model on rats. Famotidine was used as the standard antiulcer drug.
      Numerical density of ulcer areas and oxidative status were determined on stomach
      tissues of rats. RESULTS: All doses of isoorientin and methanol extract decreased
      MDA level and increased SOD activity and GSH levels in the stomach tissue of
      rats. When numerical density of ulcer areas were analized, the 500 mg/kg dose of
      methanol extract (84%) exhibited a similar effect to 20 mg/kg dose of standart
      drug famotidine (87%). CONCLUSIONS: The gastroprotective effects of E.
      spectabilis and its major constituent isoorientin in rats for the first time.
      Detailed analyses suggested that potential antioxidant activity of both plant
      extract and isoorientin mediates the gastroprotective effect.

PMID- 30110061
TI  - Is the early or delayed remote ischemic preconditioning the more effective from a
      microcirculatory and histological point of view in a rat model of partial liver
      ischemia-reperfusion?1.
AB  - PURPOSE: To compare early- and late-effect remote ischemic preconditioning (RIPC)
      by analysing the microcirculatory, hemodynamic and histological changes in
      partial liver ischemia-reperfusion of rats. METHODS: 60-minute partial liver
      ischemia followed by 120-minute reperfusion was performed without (Control group,
      n=7) or with preconditioning. In RIPC groups a tourniquet was applied around the
      left thigh using 3 cycles of 10-minute ischemia/10-minute reperfusion, one (RIPC
      1, n=7) or twenty-four hours (RIPC-24, n=7) before I/R. Hemodynamic and
      microcirculatory measurements were performed before and after ischemia and in
      30th, 60th and 120th minute of reperfusion and histological examination at the
      end of reperfusion. RESULTS: Blood pressure decreased in all groups followed by
      biphasic changes in Control group. In RIPC groups R120 values returned almost to
      normal. Heart rate increased in Control and RIPC-1 groups at R120, while RIPC-24
      did not show significant changes. Microcirculation of non-ischemic liver stayed
      constant in Control and showed significant changes in RIPC-24 group, while in
      ischemic liver elevated by R120 in all groups. RIPC didn't reduce histological
      alterations. CONCLUSION: Considering the survival and the results, both remote
      ischemic preconditioning protocols had beneficial effect in hepatic ischemia
      reperfusion, however the histopathological findings were controversial.

PMID- 30110063
TI  - NF-kB mediated CX3CL1 activation in the dorsal root ganglion contributes to the
      maintenance of neuropathic pain induced in adult male Sprague Dawley rats1.
AB  - PURPOSE: To evaluate the role of CX3CL1 and NF-kappaB in the lumbar disc
      herniation induced neuropathic pain. METHODS: After LDH induced by implantation
      of autologous nucleus pulposus (NP) on the left L5 nerve root was established,
      mechanical thresholds and thermal hyperalgesia were tested at relevant time
      points during an observation period of 28 days. Expression of CX3CL1 and NF
      kappaBin the dorsal root ganglion (DRG) were performed by using Western blotting
      and RT-PCR. RESULTS: Implantation of autologous nucleus pulposus (NP) induced
      neuropathic pain, associated with increased mRNA and protein expression of CX3CL1
      in the DRG. Moreover, intrathecal injection of neutralizing antibody against
      CX3CL1 could attenuates LDH-induced persistent pain hypersensitivity.
      Interestingly, NF-kappaB activation in the DRGs were found in LDH-induced
      neuropathic pain. Furthermore, NF-kappaB downregulation by p65 inhibitor PDTC
      markedly alleviated LDH-induced mechanical allodynia and thermal hyperalgesia in
      rat. Importantly, CX3CL1 neutralizing antibody (10 MUg/10 MUl, i.t.) reduces p
      p65 protein level in DRG. CONCLUSIONS: CX3XL1 could regulate LDH-induced
      neuropathic pain through NF-kappaB pathway. Targeting CX3CL1 and NF-kappaB may
      represent a potential treatment for neuropathic pain caused by LDH.

PMID- 30110064
TI  - Immunoexpression of vascular endothelial growth factor and B-cell lymphoma 2 in
      the uterine tissue of rats treated with melatonin in the estrus phase1.
AB  - PURPOSE: To investigate the effect of melatonin on uterine tissue in the
      ovariectomized rat model. METHODS: Fourty Wistar albino rats were divided into
      four groups for histologic and immunohistochemical examination. The rats were
      first numbered randomly and then randomly divided into 4 equal groups: control
      (group 1), torsion (group 2), torsion+detorsion (group 3) and
      torsion+detorsion+melatonin (group 4) groups. In addition, four Wistar albino
      rats were used for western blot analysis in each group. And also, malondialdehyde
      (MDA) levels were measured biochemically in all rats. RESULTS: The
      histopathological examination of the uterine tissue in rats ovarectomized showed
      a degeneration in uterine glands, dilation of blood vessels in the internal layer
      with a thrombosis and bleeding, abnormal nucleuses and vacuolated cytoplasm above
      and below the nucleus. In torsion group, the apoptotic cells increased in luminal
      epithelium and gland cells. In the melatonin group showed that the Bcl2 negative
      effect on the uterine epithelium and did not lead to apoptotic cells. CONCLUSION:
      The increase in vascular endothelial growth factor expression resulted in the
      rearrangement of endothelial cell growth and the induction of angiogenesis.

PMID- 30110066
TI  - Erratum.
AB  - [This corrects the article doi: 10.1590/s0102-865020180060000007].

PMID- 30110065
TI  - Immunhistochemical analysis of Nuclear Factor Kappa Beta expression in
      etiopathogenesis of ovarian tumors1.
AB  - PURPOSE: To investigate the place of the transcription factor nuclear kappa B (NF
      kB), which is a marker of chronic inflammation, in the etiology of the ovarian
      carcinoma. METHODS: NFkB analysis with the immunohistochemical method has been
      performed. To evaluate immunohistochemical NF-kB expression in the ovarian
      tissue, the H-score method. H-score = ? Pi (i+1), where ''Pi'' is the percentage
      of stained cells in each intensity category (0-100%) and ''i'' is the intensity
      indicating weak (i=1), moderate (i=2) or strong staining (i=3). RESULTS: It has
      been seen that, the mean H score is statistically significantly higher in the
      patient group with serous and musinous adenocarcinoma diagnosis than the two
      other patient groups (p<0.005). CONCLUSIONS: Factor nuclear kappa B is an
      important mediator that acts in the chronic inflammation. The highest expression
      rates are determined by the immunohistochemical method in the ovarian cancer
      group.

PMID- 30110067
TI  - Human papillomavirus infection and cervical cancer precursor lesions in women
      living by Amazon rivers: investigation of relations with markers of oxidative
      stress.
AB  - Objective To investigate the relation between oxidative stress markers, human
      papillomavirus infection and cervical cancer precursor lesions. Methods The study
      comprised women aged 14 to 60 years living in communities located by Amazon
      rivers in the state of Para (Itaituba, Limoeiro do Ajuru and Braganca, 126, 68
      and 43 women respectively). Papanicolau smears and polymerase chain reaction
      tests for human papillomavirus DNA detection were performed. Blood samples were
      collected to test malondialdehyde, total and oxidized glutathione levels. Results
      Malondialdehyde, total and oxidized glutathione concentrations did not differ
      significantly (p>0.05) between women with and without low-grade squamous
      intraepithelial lesions across communities. Malondialdehyde levels (8.02nmols/mL)
      were almost five times higher in human papillomavirus-positive compared to human
      papillomavirus-negative women (1.70nmols/mL) living in Itaituba (statistically
      significant difference; p<0.05). Malondialdehyde levels did not differ
      significantly (p>0.05) between human papillomavirus-positive and human
      papillomavirus-negative women living in remaining communities. Significant
      (p<0.05) differences in total glutathione levels between human papillomavirus
      positive and human papillomavirus-negative women (8.20MUg/mL and 1.47MUg/mL,
      respectively) were limited to those living in Braganca. Conclusion
      Malondialdehyde and total glutathione levels were significantly associated with
      human papillomavirus infection. However, lack of similar associations with
      squamous lesions suggest oxidative stress alone does not explain correlations
      with cervical carcinogenesis. Other factors may therefore be involved.

PMID- 30110068
TI  - Circumcision: postoperative complications that required reoperation.
AB  - Objective To evaluate post-operative complications of circumcision requiring
      surgical reintervention. Methods Retrospective analysis of medical records of
      patients submitted to circumcision from May 1st, 2015 to May 31st, 2016. Results
      A total of 2,441 circumcisions were performed; in that, 1,940 using Plastibell
      and 501 by the classic technique. Complications requiring surgical reintervention
      were found in 3.27% of patients. When separated by surgical technique, 3.4% of
      circumcisions using Plastibell device required reoperation, as compared to 3% of
      conventional technique (p=0.79). Preputial stenosis was most frequently found in
      classic circumcision, with statistical significance (p<0.001). Bleeding was more
      frequent when using Plastibell device, but the difference was not statistically
      different (p=0.37). Patients' age was also evaluated to investigate if this
      variable influenced on the postoperative outcome, but no significant difference
      was found. Conclusion There was no statistically significant difference when
      comparing complications between the different techniques performed at this
      hospital. Preputial stenosis was most frequently found in the classic
      circumcision, while bleeding was more prevalent when using Plastibell device.
      Patients' age did not influence in complications.

PMID- 30110069
TI  - Relationships between female infertility and female genital infections and pelvic
      inflammatory disease: a population-based nested controlled study.
AB  - OBJECTIVES: Our purpose was to examine the associations of female genital
      infections and certain comorbidities with infertility. METHODS: The Taiwan
      National Health Research Database was searched for women with a new diagnosis of
      infertility between 2000 and 2013. Women without a diagnosis of infertility
      served as a control group and were matched with the infertility cases by age (+/
      3 years) and index year. They were divided into two groups: <=40 years old and
      >40 years old. Univariate and multivariate conditional logistic regression models
      were employed to identify the risk factors associated with infertility. RESULTS:
      A total of 18,276 women with a new diagnosis of infertility and 73,104 matched
      controls (mean cohort age, 31+/-6.2 years) were included. According to the
      adjusted multivariate analysis, pelvic inflammatory disease involving the ovary,
      fallopian tube, pelvic cellular tissue, peritoneum (odds ratio (OR)=4.823), and
      uterus (OR=3.050) and cervical, vaginal, and vulvar inflammation (OR=7.788) were
      associated with an increased risk of infertility in women aged <=40 years. In
      women aged >40 years, pelvic inflammatory disease of the ovary, fallopian tube,
      pelvic cellular tissue, and peritoneum (OR=6.028) and cervical, vaginal, and
      vulvar inflammation (OR=6.648) were associated with infertility. Obesity, lipid
      metabolism disorders, dysthyroidism, abortion (spontaneous or induced), bacterial
      vaginosis, endometritis, and tubo-ovarian abscess were associated with an
      increased risk of infertility according to the univariate analysis but not the
      multivariate analysis. CONCLUSIONS: Female genital tract infections, but not the
      comorbidities studied here, are associated with an increased risk of infertility.

PMID- 30110070
TI  - ERRATUM: Structural insights into Plasmodium falciparum nicotinamide
      mononucleotide adenylyltransferase: oligomeric assembly".
AB  - [This corrects the article doi: 10.1590/0074-02760180073].

PMID- 30110071
TI  - Erratum: Psychosocial care network: adequacy of roles and functions performed by
      professionals.
AB  - [This corrects the article doi: 10.1590/1983-1447.2018.57448].

PMID- 30110073
TI  - Self-reported assessment of female sexual function among Brazilian undergraduate
      healthcare students: a cross-sectional study (survey).
AB  - BACKGROUND: The present study aimed to evaluate female sexual function among
      young undergraduate women. DESIGN AND SETTING: Cross-sectional survey conducted
      among Brazilian undergraduate students. METHODS: This study used online
      questionnaires to assess sociodemographic and health-related data and used the
      Brazilian version of the Female Sexual Function Index (FSFI) among female
      undergraduate students aged 18 to 25 years who were regularly enrolled in
      undergraduate healthcare courses. The FSFI is composed of 19 items that measure
      female sexual function over the last four weeks, in six domains: desire and
      subjective stimulation, sexual arousal, lubrication, orgasm, satisfaction and
      pain or discomfort. RESULTS: Among the 149 female undergraduate students
      evaluated, 43 (28.8%) presented sexual dysfunction (score < 26.55). Health
      conditions were not associated with female sexual dysfunction. Among the women
      with sexual dysfunction, all domains of the sexual response cycle were affected
      (P < 0.001). CONCLUSIONS: Sexual dysfunction was identified in at least a quarter
      of these young undergraduate women and it was not associated with gynecological
      problems, menstrual cycles, dysmenorrhea, contraceptive use or physical activity.

PMID- 30110072
TI  - Plasmodium falciparum parasites overexpressing farnesyl diphosphate
      synthase/geranylgeranyl diphosphate synthase are more resistant to risedronate.
AB  - Farnesyl diphosphate synthase/geranylgeranyl diphosphate synthase (FPPS/GGPPS) is
      a key enzyme in the synthesis of isoprenic chains. Risedronate, a bisphosphonate
      containing nitrogen (N-BP), is a potent inhibitor of blood stage Plasmodium.
      Here, we show that P. falciparum parasites overexpressing FPPS/GGPPS are more
      resistant to risedronate, suggesting that this enzyme is an important target, and
      bisphosphonate analogues can be used as potential antimalarial drugs.

PMID- 30110074
TI  - Prevalence of Entamoeba histolytica and other enteral parasitic diseases in the
      metropolitan region of Belo Horizonte, Brazil. A cross-sectional study.
AB  - BACKGROUND: Enteral parasitic diseases are a public health problem in nations
      with low economic development and in settings with poor sanitation. Amebiasis is
      the second most frequent form of parasitosis, with a high burden of disease.
      Knowledge of the prevalence of enteroparasitoses in a given region is useful for
      planning clinical decision-making. Thus, the aim of this study was to estimate
      the prevalence of enteral parasitic diseases, especially amebiasis, through
      analysis on stool samples from public and private laboratories in a metropolitan
      area in southeastern Brazil. DESIGN AND SETTING: Cross-sectional study conducted
      in the metropolitan region of Belo Horizonte, Brazil. METHODS: We evaluated 6,289
      fecal samples from one private and one public laboratory. The samples were
      concentrated by means of spontaneous sedimentation, and those that were positive
      for Entamoeba histolytica or Entamoeba dispar in optical microscopy analyses were
      processed to obtain deoxyribonucleic acid, with subsequent identification through
      the polymerase chain reaction. RESULTS: Among the stool samples, 942 (15.0%) had
      parasitic infections; 73 (1.2%) of these were helminthic infections and 847
      (13.5%) were protozoan infections, caused mainly by Escherichia coli (6.0%),
      Endolimax nana (5.2%) and Giardia lamblia (1.2%). Infections due to Entamoeba
      histolytica or Entamoeba dispar occurred in 36 samples (0.6%) and the polymerase
      chain reaction revealed five (13.9%) as Entamoeba histolytica. CONCLUSION: The
      prevalence of enteral parasitic diseases is high in the metropolitan region of
      Belo Horizonte, although amebiasis may not be a problem.

PMID- 30110075
TI  - Relationship between socioeconomic and nutritional status in the Serbian adult
      population: a cross-sectional study.
AB  - BACKGROUND: Socioeconomic status is a well-known risk factor for obesity. The aim
      of this study was to assess the relationship between socioeconomic and
      nutritional status in the Serbian adult population. DESIGN AND SETTING: Cross
      sectional study on data from the 2013 National Health Survey performed in Serbia.
      METHODS: The study population consisted of adults aged >= 20 years. Face-to-face
      interviews and anthropometric measurements were conducted by trained staff.
      Associations between body mass index and sociodemographic variables were analyzed
      using multivariable logistic regression analyses. RESULTS: Out of 12,461 subjects
      of both sexes, 36.4% were overweight and 22.4% were obese. The prevalences of
      overweight and obesity differed significantly between the sexes, regarding all
      sociodemographic characteristics. Among women, educational attainment was
      associated with lower risk of being overweight (odds ratio, OR = 0.82; 95%
      confidence interval, CI: 0.69-0.98 for medium-level and OR = 0.77; CI: 0.62-0.97
      for higher education) or obese (OR = 0.68; CI: 0.57-0.82 for medium-level and OR
      = 0.41; CI: 0.31-0.54 for higher education). In contrast, medium-level (OR =
      1.28; CI: 1.08-1.52) and highly educated men (OR = 1.39; CI: 1.11-1.74) were more
      frequently overweight than were those with low education. Among men, grade I
      obesity was positively related to the richest wealth index group (OR = 1.27),
      while the opposite was true for grade II obesity among women (OR = 0.61).
      CONCLUSION: This study showed significant socioeconomic inequalities in
      nutritional status between men and women. Continuous monitoring of socioeconomic
      patterns relating to weight is important, especially with further exploration of
      the link between education and obesity.

PMID- 30110076
TI  - Incorrect use of inhalation devices among patients with bronchial asthma. A
      hospital-based cross-sectional study in Rio de Janeiro, Brazil.
AB  - CONTEXT AND OBJECTIVE: Treatment of asthma implies inhalation of specific drugs
      to reach high concentrations in the respiratory tree and ensure low drug
      bioavailability and few adverse effects. This study aimed to evaluate the
      effectiveness of the inhalation technique among outpatients with asthma. DESIGN
      AND SETTING: Tertiary-care hospital-based cross-sectional study in Rio de
      Janeiro. METHODS: We evaluated inhalation practices in a convenience sample. A
      questionnaire was used to investigate sociodemographic data and assess disease
      control level, duration of use of the inhalation device, length of treatment and
      previous instructions provided by the prescribing physician. Patients
      demonstrated their inhalation technique using empty devices, and their technique
      was considered correct when all steps were appropriately performed or when errors
      did not interfere with the treatment outcome. RESULTS: Among the 71 participants,
      53 (74.7%) had been using the same inhaler device for at least two years and 41
      (57.8%) had been under treatment for two years or more. Twelve (17.1%) said that
      they had been taught once and 57 (81.4%) at least twice, while one (1.4%)
      reported not having received any guidance regarding use of inhaler devices.
      Eighteen patients (25.3%) presented controlled asthma and 28 (39.5%) performed
      the inhalation technique correctly. Incorrect technique was associated with fewer
      evaluations of the inhalation technique (P =0.04) and uncontrolled asthma (P =
      0.01). CONCLUSIONS: Less than half of the sample performed the inhalation
      technique correctly. Incorrect inhalation technique was related to lower number
      of evaluations of the use of the inhalation device and uncontrolled asthma.

PMID- 30110077
TI  - Relationship between premenstrual syndrome and basic personality traits: a cross
      sectional study.
AB  - BACKGROUND: Although many studies have investigated premenstrual syndrome and
      related factors, there is still only a limited number of studies investigating
      the relationship between premenstrual syndrome and basic personality traits. This
      study was conducted to investigate the association between premenstrual syndrome
      and basic personality traits among university students. DESIGN AND SETTING: Cross
      sectional analytical study conducted in a city in western Turkey. METHODS: The
      Premenstrual Syndrome Scale, the Basic Personality Traits Scale and a
      questionnaire on sociodemographic characteristics developed by the present
      researchers were applied to 490 female students at the College of Health Sciences
      of a state university. RESULTS: Premenstrual syndrome was more common among
      students living in rural areas (65.1%), students with chronic diseases (74.1%),
      students who suffered from menstrual cramps (61.1%), students who used cigarettes
      (72.1%) and students with alcohol intake (65.5%). In the final model of the
      logistic regression analysis, presence of pain during the menstrual period
      increased the risk of presence of PMS by a factor of 1.554 (95% confidence
      interval, CI: 1.033-2.336; P = 0.034) and high scores on the total basic
      personality traits scale increased it by a factor of 1.016 (95% CI: 1.002-1.030;
      P = 0.029). The prevalence of premenstrual syndrome was found to be higher among
      students who were less extrovert (P = 0.007) and less conscientious (P = 0.001);
      and among students with higher neuroticism (P = 0.000) and negative valance (P =
      0.000). CONCLUSION: This study demonstrates that personality may be associated
      with premenstrual syndrome.

PMID- 30110078
TI  - Sensitivity and specificity of ultrasonography in diagnosing supraspinatus
      lesions: a prospective accuracy diagnostic study.
AB  - BACKGROUND: This study was designed to define the accuracy of shoulder
      ultrasonography for diagnosing supraspinatus tendon tears. This examination is
      routinely used by orthopedists and may do away with the need for other
      examinations for diagnosing these tendon injuries. The aim of this study was to
      evaluate the sensitivity and specificity of shoulder ultrasonography for
      diagnosing supraspinatus tendon injuries, using magnetic resonance imaging as the
      reference. DESIGN AND SETTING: Prospective accuracy study at a single center: the
      Shoulder and Elbow Surgery Clinic of the Department of Orthopedics and
      Traumatology. METHODS: Shoulder ultrasonography was performed on 80 patients of
      both genders, over 18 years of age, with complaints of shoulder pain and
      clinically suspected supraspinatus tendon lesions. Jobe's test and a full can
      test were performed. In addition, they underwent magnetic resonance imaging in a
      3.0-tesla machine, as the reference standard. The examinations were performed and
      interpreted by radiologists. RESULTS: Ultrasonography showed sensitivity of 36.3%
      and specificity of 91.7% for supraspinatus tears overall: sensitivity of 25.8%
      and specificity of 91.8% for partial tears and sensitivity of 46.2% and
      specificity of 100% for full-thickness tears. Ultrasonography showed high
      accuracy for diagnosing full-thickness tears: 91.3%. The p-values were 0.003 for
      tears overall, 0.031 for partial tears and < 0.001 for full-thickness tears.
      CONCLUSIONS: Ultrasonography showed low sensitivity for detecting supraspinatus
      tears, but high specificity for both partial and full-thickness tears.

PMID- 30110079
TI  - Family functioning and quality of life among children with anxiety disorder and
      healthy controls. A cross-sectional study.
AB  - BACKGROUND: Studies have shown that children with anxiety disorders (ADs) present
      impaired family functioning and quality of life. We aimed to evaluate family
      functioning and quality of life among children with AD and healthy controls.
      DESIGN AND SETTING: Cross-sectional study (survey) at two centers in Turkey.
      METHODS: The study group comprised 42 children diagnosed with AD and 55 controls.
      The Screen for Child Anxiety-Related Emotional Disorders (SCARED) questionnaire
      was filled out by their parents to measure the severity of anxiety symptoms.
      Family functioning among the children was assessed using the Family Assessment
      Device (FAD) and Parental Attitude Research Instrument (PARI). The children's
      quality of life was assessed through the Pediatric Quality of Life Inventory
      (PedsQL). RESULTS: The children's average age was 10.00 +/- 0.21 years in the AD
      group and 9.98 +/- 1.53 years among the controls. There were higher scores on all
      FAD subscales in the AD group (2.15 +/- 0.52; 2.29 +/- 0.44; 2.44 +/- 0.55; 2.10
      +/- 0.61; 2.56 +/- 0.40; 2.32 +/- 0.33; and 2.29 +/- 0.47). On PARI subscales,
      there were significant differences favoring the AD group (p < 0.05), except for
      democratic attitude. All PedsQL subscales differed significantly between the
      groups, favoring the AD group. A statistically significant relationship was found
      between all PedsQL subscales and SCARED scores in the AD group. CONCLUSION: We
      found that both family functioning and quality of life among children with AD
      were negatively affected. However, further studies with larger sample sizes are
      required to reach stronger conclusions.

PMID- 30110080
TI  - Germination constraints of dicarpic cypselae of Bidens pilosa L.
AB  - Bidens pilosa L. is a heterocarpic weed species with two cypselae types that
      present morpho-physiological differences, being the peripheral type smaller and
      slower to germinate than the central one. We aimed to verify how the germination
      mechanism varied between types. We focused on two mechanisms: (1) pericarp
      constraints (physical and chemical) and (2) hormonal stimulation (Abcisic acid
      [ABA] and Gibberellin [GA]). Both cypselae types are physically constrained by
      the pericarp, for when it is excised both seed types increase their germination,
      but behavioral differences still remain. The pericarp of the peripheral type also
      has chemical inhibitors that effectively inhibited germination of the intact
      central cypsela. To test the hormonal effects, we focused on the ABA:GA control.
      Both cypselae responded to an exogenous ABA concentration gradient, however there
      is no variation between types on the sensitivity to it. Also, both cypselae types
      were indifferent to Fluridone (ABA inhibitor), which indicates that the dormancy
      is not maintained by de novo ABA synthesis. Cypselae types had different
      sensitivity to an exogenous GA3 gradient, the central type being more sensitive
      to the treatment than the peripheral one. But when the endogenous GA synthesis
      was blocked by Paclobutrazol, both types responded equally to same GA3
      concentrations. This indicates that endogenous GA synthesis may be related to
      differences observed on germination of cypselae types. To conclude, seed types
      differ on their growth potential to overcome the pericarp resistance: while the
      inhibitor in the peripheral pericarp reduces growth potential, GA increases it.

PMID- 30110081
TI  - Historical records of orchid bees (Apidae: Euglossini) in Belem Endemism Center:
      species list of 92 years sampling.
AB  - The distribution of most species occurs in delimited regions with unique
      characteristics called "centers of endemism". In Eastern Amazon is located the
      Belem Endemism Center (BEC), one of the most intensely deforested in Brazilian
      Amazon. Here, we show information about orchid bee assemblages based on
      historical records from entomological collections. For each species, we
      calculated occurrence frequency and dominance, and we classified them in 3
      statuses: common, intermediate or rare species. Curves of observed and estimated
      richness were built, based on Jackknife estimator. We found 1,257 specimens from
      56 species, constituting records from 1917 to 2009, and one species is a new
      record for BEC. Higher number of specimens and species was concentrated in a few
      locations and surveys increased from the 70's. The results suggest a high
      richness of orchid bees in the BEC, although this scenario is far from what is
      expected for the entire area. The high occurrence of rare species may be related
      to their low representativeness in the collections, and the proximity between the
      areas had favored samplings. Even so, the species list and the conservation
      status presented here may be useful information in studies comparing past and
      current orchid bee fauna, and, allied to data on bees' responses to land use
      changes occurred in BEC over the years, can fit as a basis for defining priority
      areas for conservation.

PMID- 30110082
TI  - Life-history traits of Farlowella hahni (Siluriformes, Loricariidae) in streams
      of the Ivinhema River Basin, Upper Parana Basin.
AB  - Brazilian laws allow the catch of some species as ornamental fish; however, in
      the absence of biological information, such catch can threaten species
      conservation. Therefore, this study aimed to offer population and reproductive
      information about Farlowella hahni in streams of the Ivinhema River Basin, Upper
      Parana Basin. To accomplish this, a total of 165 F. hahni individuals were
      analyzed, including 109 females and 48 males, resulting in an important sex ratio
      difference from 1:1 (chi 2=19.97; p<0.001), indicating a predominance of females
      throughout the year. Females reach higher standard length than males. Males
      presented isometric Length-Weight Relationships, while females have positive
      allometric growth. Gonadosomatic index presented higher values from October
      through December. The mean fecundity was 100.3+/-36.4 of vitellogenic oocytes and
      was positively correlated with standard length (r=0.51; p=0.01). The data
      presented herein are the first for this species and suggest a need to carefully
      manage the F. hahni population, considering its low abundance and fecundity.

PMID- 30110083
TI  - The South American lungfish Lepidosiren paradoxa as a new host for Trichodina
      quelenii.
AB  - Recently, the South American lungfish Lepidosiren paradoxa is being found inside
      aquaculture ponds, and even though there are a few studies on their parasite
      fauna, there is still much to be reported. Thus, the objective of this study is
      to report parasitism by trichodinids in L. paradoxa, as these ciliate protozoa
      are related to injuries and mortality in fish farming. The lungfish were
      collected from experimental tanks, had their tegument scraped and the resultant
      mucus was analyzed under an optical microscope for morphological and
      morphometrical analyses in Giemsa and silver nitrate stained slides. The species
      found was identified as Trichodina quelleni. This is the first report of this
      parasite in L. paradoxa, and the second report in cultivated fish in Brazil.

PMID- 30110084
TI  - Cytokines, cortisol, and nitric oxide as salivary biomarkers in oral lichen
      planus: a systematic review.
AB  - The etiopathogenesis of oral lichen planus (OLP) is still not fully elucidated,
      and it is believed that its development could involve a neuro-immune-endocrine
      profile. This systematic review investigated the relationship between cytokines,
      cortisol, and nitric oxide (NO) in the saliva of OLP patients. An electronic
      search was conducted in Pubmed/Medline, Scopus, LIVIVO, and Web of Science
      databases with no restriction of language to identify studies published up to
      December 2017. Data extraction was performed using the Preferred Reporting Items
      for Systematic Review and Meta-Analyses (PRISMA) guidelines. A total of 140
      articles were retrieved, and 32 articles fulfilled the inclusion criteria
      (cytokines = 17; cortisol = 9; NO = 6). The most studied cytokines in the saliva
      of OLP patients were interleukins IL-4, IL-6, IL-8, IFN-?, and TNF-alpha, which
      were higher in OLP patients than in healthy controls (HC). Salivary cortisol was
      found to be higher in OLP than in HC in most (55.5%) of the selected studies, and
      all studies related to NO found higher levels of this marker in OLP than in HC.
      Despite controversial results, our review suggests that OLP patients have an
      increased inflammatory response, as indicated by the proinflammatory profile of
      salivary cytokines. In addition, we conclude that salivary cytokine and NO
      measurements may have significant diagnostic and prognostic potential for
      monitoring disease activity and therapeutic responses in OLP.

PMID- 30110085
TI  - Enamel defects and tooth eruption disturbances in children with sickle cell
      anemia.
AB  - Sickle cell anemia, a genetic disease caused by a mutation in the beta-globin
      gene, can present oral manifestations such as delayed tooth eruption and
      hypomineralized enamel and dentin. The aim of the present study was to evaluate
      the prevalence and severity of developmental defects of enamel (DDE) and delayed
      tooth eruption in children with sickle cell anemia. The sample comprised 56 male
      and female children with sickle cell anemia aged 6 to 12 years and treated at the
      Hematology and Hemotherapy Center of Pernambuco, Brazil. The data were collected
      according to the WHO criteria for DDE and tooth eruption. The prevalence of DDE
      was 58.2% and increased with age, affecting 43.8% of children aged 6 to 8 years
      and 66.7% of those aged 10 to 12 years (p>0.05; Pearson's chi-square test). There
      was no significant association between DDE and sex; the most prevalent type of
      DDE was diffuse opacity (6.2%). Tooth eruption was delayed in 18 children
      (32.1%). The delay increased with age and was detected in 11.8% of children aged
      6 to 8 years, in 20.0% of those aged 8 to 10 years and in 54.2% of those aged 10
      to 12 years (p<0.05; Pearson's chi-square test). Delayed tooth eruption was
      higher in males (36.7%, p>0.05). The prevalence of DDE was high, increased with
      age and was similar between sexes, while delayed eruption was higher in males and
      showed a significant association with age.

PMID- 30110086
TI  - A novel ultrasonic tip for removal of filling material in flattened/oval-shaped
      root canals: a microCT study.
AB  - The aim of this study was to evaluate the influence of a novel ultrasonic tip as
      an auxiliary method for removing filling material from flattened/oval-shaped
      canals. The null hypothesis tested was that this method does not influence
      removing the filling material in flattened/oval-shaped canals. Forty-five
      mandibular incisors were selected and randomly divided into three experimental
      groups (n = 15) according to different protocols for removing root canal filling
      material. Group R: Reciproc R25/.08, Group RC: Reciproc R25/.08 + Clearsonic tip,
      and Group CR: Clearsonic tip + Reciproc R25/.08. The teeth were scanned pre and
      post-operatively by means of a micro-computed tomography system. Data were
      analyzed using non-parametric Kruskal-Wallis and Dunn tests (p < 0.05). The
      percentage of residual root canal filling material between the experimental
      groups was examined. Statistically significant differences between the
      experimental groups were found in the root canal. Group R had the highest
      percentage of residual root canal filling material when compared with Groups RC
      and CR. The lowest percentage of residual root canal filling material was
      observed in Group CR. In the apical third of the root canal, statistically
      significant differences were found between the different protocols. The use of
      the ClearSonic tip followed by the Reciproc 25/.08 file to remove filling
      material resulted in the lowest percentage of residuals in the whole root canal
      and in the apical third.

PMID- 30110087
TI  - Prevalence of and factors associated with enamel fracture and other traumas in
      Brazilian children 8-10 years old.
AB  - The aim of this study was to assess the prevalence and discriminate the
      associated factors between enamel fractures and other trauma/trauma sequelae in 8
      to 10-year-old Brazilian schoolchildren. A representative sample of 1,201
      children from public and private schools were enrolled in this cross-sectional
      study. Questionnaires about sociodemographic characteristics were answered by
      parents. The outcome variable (traumatic dental injury, TDI) was multi
      categorized. Independent individual variables were sex, age, number of residents
      in household, parents/caregivers' level of education, family income, dental
      caries, and overjet. Type of school was considered an independent contextual
      variable. Multilevel analysis, bivariate, and multivariate multinomial logistic
      regression models were performed. The prevalence of TDI was 14.0% (2.8% with
      other trauma/trauma sequelae). The multilevel analysis revealed no significant
      difference between the type of school and TDI. The multinomial logistic
      regression showed that boys (OR = 2.3; 95%CI: 1.1-4.8), older children (OR = 1.8;
      95%CI: 1.1-3.0) and individuals with an overjet > 3 mm (OR = 2.5; 95%CI: 1.0-6.2)
      were more likely to present other trauma/trauma sequelae. Enamel fracture was not
      significantly associated with any variables. The prevalence of TDI in 8 to 10
      year-old schoolchildren was 14% but only 2.8% of other trauma/trauma sequelae.
      Differences regarding the associated factors of TDI involving enamel fracture or
      other trauma/trauma sequelae were detected, suggesting that the different TDI
      classification cannot be evaluated as a single category.

PMID- 30110088
TI  - Short term histopathological effects of GaAlAs laser on experimentally induced
      TMJ osteoarthritis in rabbits.
AB  - The aim of this study was to evaluate the biostimulation (BS) effect of the
      gallium-aluminum-arsenide (GaAlAs) diode laser by histopathology with an
      experimental osteoarthritis (OA) model in the temporomandibular joints (TMJ) of
      rabbits, in the early period. GaAlAs diode laser is used for pain reduction in
      TMJ disorders. Twenty-four adult male New Zealand white rabbits were randomly
      divided into three equal groups: Control Group (CG), Study Group 1 (SG-1), and
      Study Group 2 (SG-2). Mono-iodoacetate (MIA) was administered to the right TMJs
      of all rabbits. The rabbits did not undergo any treatment for four weeks to allow
      the development of osteoarthritis. In SG-1, laser BS was applied to the rabbits
      at 940 nm, 5 W, and 15 J/cm2 in continuous wave mode at 48-hour intervals for 14
      sessions; and in SG-2, laser BS was applied with the same parameters at 24-hour
      intervals for 28 sessions. Laser BS was not applied to the rabbits in CG. All
      rabbits were sacrificed simultaneously. The TMJ cartilage, osteochondral
      junction, chondrocyte appearance, and subchondral ossification were evaluated
      histopathologically. There was no statistically significant difference between
      the groups in terms of cartilage, osteochondral junction, chondrocyte appearance,
      and subchondral ossification values (p > 0.05). The laser BS protocol used in the
      study had no positive histopathological effects on TMJ OA in the early period.

PMID- 30110089
TI  - Hypericum perforatum chronic treatment affects cognitive parameters and brain
      neurotrophic factor levels.
AB  - OBJECTIVE: To evaluate the effects of Hypericum perforatum (hypericum) on
      cognitive behavior and neurotrophic factor levels in the brain of male and female
      rats. METHODS: Male and female Wistar rats were treated with hypericum or water
      during 28 days by gavage. The animals were then subjected to the open-field test,
      novel object recognition and step-down inhibitory avoidance test. Nerve growth
      factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line
      derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and
      frontal cortex. RESULTS: Hypericum impaired the acquisition of short- and long
      term aversive memory in male rats, evaluated in the inhibitory avoidance test.
      Female rats had no immediate memory acquisition and decreased short-term memory
      acquisition in the inhibitory avoidance test. Hypericum also decreased the
      recognition index of male rats in the object recognition test. Female rats did
      not recognize the new object in either the short-term or the long-term memory
      tasks. Hypericum decreased BDNF in the hippocampus of male and female rats.
      Hypericum also decreased NGF in the hippocampus of female rats. CONCLUSIONS: The
      long-term administration of hypericum appears to cause significant cognitive
      impairment in rats, possibly through a reduction in the levels of neurotrophic
      factors. This effect was more expressive in females than in males.

PMID- 30110092
TI  - Patient safety culture in a university hospital.
AB  - OBJECTIVE: to assess patient safety culture in a university hospital. METHOD:
      cross-sectional study with data collection through the Hospital Survey on Patient
      Safety Culture applied in electronic device. A total of 381 employees were
      interviewed, corresponding to 46% of the sum of eligible professionals. Data were
      analyzed descriptively. the Cronbach's alpha was used to calculate the frequency
      and reliability. RESULTS: most were women (73%) from the nursing area (50%) and
      with direct contact with patients (82%). The composites related to "teamwork
      within units" (58%, alpha=0.68), "organizational learning - continuous
      improvement" (58%, alpha=0.63), "supervisor/manager expectations and actions
      promoting patient safety" (56%, alpha=0.73) had higher positive responses. Nine
      composites had low positive responses, with emphasis on "nonpunitive response to
      error" (18%, alpha=0.40). Only the item "in this unit, people treat each other
      with respect" had positive response above 70%. The patient safety assessment in
      the work unit was positive for 36% of employees, however only 22% reported events
      in past year. CONCLUSION: the findings revealed weaknesses in the safety culture
      at the hospital, with emphasis on culpability.

PMID- 30110090
TI  - Intermittent hypoxia, brain glyoxalase-1 and glutathione reductase-1, and anxiety
      like behavior in mice.
AB  - OBJECTIVE: Sleep apnea has been associated with anxiety, but the mechanisms of
      the sleep apnea-anxiety relationship are unresolved. Sleep apnea causes oxidative
      stress, which might enhance anxiety-like behavior in rodents. To clarify the
      apnea-anxiety connection, we tested the effect of intermittent hypoxia, a model
      of sleep apnea, on the anxiety behavior of mice. METHODS: The rodents were
      exposed daily to 480 one-minute cycles of intermittent hypoxia to a nadir of 7+/
      1% inspiratory oxygen fraction or to a sham procedure with room air. After 7
      days, the mice from both groups were placed in an elevated plus maze and were
      video recorded for 10 min to allow analysis of latency, frequency, and duration
      in open and closed arms. Glyoxalase-1 (Glo1) and glutathione reductase-1 (GR1)
      were measured in the cerebral cortex, hippocampus, and striatum by Western
      blotting. RESULTS: Compared to controls, the intermittent hypoxia group displayed
      less anxiety-like behavior, perceived by a statistically significant increase in
      the number of entries and total time spent in open arms. A higher expression of
      GR1 in the cortex was also observed. CONCLUSION: The lack of a clear anxiety
      response as an outcome of intermittent hypoxia exposure suggests the existence of
      additional layers in the anxiety mechanism in sleep apnea, possibly represented
      by sleepiness and irreversible neuronal damage.

PMID- 30110093
TI  - Planning pathways in the transfer of Directly Observed Treatment of Tuberculosis.
AB  - OBJECTIVE: to investigate the planning pathways in the transfer of Directly
      Observed Treatment of tuberculosis. METHOD: a qualitative study conducted using
      interviews and a semi-structured guide, administered to five subjects who were
      among the coordinators and managers of the tuberculosis control programs, and the
      secretary of health of a municipality in the south of Brazil. Situational
      Strategic Planning and Discourse Analysis of the French matrix were the
      theoretical and analytical references used, respectively. RESULTS: three
      reflexive axes were identified: weaknesses in the process of planning the
      Directly Observed Treatment transfer, antagonism between planning and daily
      requirements and formulation of planning and execution. Lack of systematization
      regarding the planning and execution for transfer the Directly Observed Treatment
      policy, demonstrates the fragility and incipience of this activity, and the
      possibility of its non-existence. CONCLUSION: the urgent need for managers and
      coordinators to better appropriate the theoretical framework for changing public
      policies, and the related planning mechanisms, includes a proposal for
      reorganization and qualification of the diffusion process, both practical
      operative and political-organization.

PMID- 30110091
TI  - Effectiveness of nursing intervention for increasing hope in patients with
      cancer: a meta-analysis.
AB  - OBJECTIVE: to evaluate the efficacy of nursing interventions to increase the
      level of hope in cancer patients, in a meta-analysis. METHODS: electronic
      databases were searched. Two of the authors independently extracted data from the
      eligible studies, and Stata 13.0 software was used to pool the data. RESULTS:
      nine randomized controlled trials were included, and methodological quality of
      each randomized controlled trial (RCT) was evaluated using Cochrane handbook
      recommendations. A random effects model was used to combine results from eligible
      studies. The pooled results using the fixed effects model showed that scores to
      first effects increase significantly after the use of nursing intervention
      between the groups. Heterogeneity was observed among the studies for posttest (df
      = 8, P = 0.000; I2 =76.1 %). The results indicated significant heterogeneity
      across the nine selected studies. The test for heterogeneity showed no
      homogeneity among studies for follow-up (df = 8, P = 0.328; I2 = 12.9 %), and
      there was no statistical significance. CONCLUSION: the current evidence suggests
      that nursing intervention has a positive effect on hope in cancer patients.
      However, more large-scale and high-quality randomized controlled trials are
      needed to confirm these results.

PMID- 30110095
TI  - Patient safety in nursing care during medication administration.
AB  - OBJECTIVE: to evaluate the conformity of care practices of the nursing team
      during the administration of drugs through central vascular catheter. METHOD: a
      descriptive, prospective, observational study conducted in an Intensive Care
      Unit. The non-probabilistic intentional sample consisted of 3402 observations of
      drug administrations in patients with central vascular catheters. The previously
      validated collection instrument was constructed based on the Guideline for
      Prevention of Intravascular catheter-related infections. Data was collected
      through direct observations of nursing practices performed by the nursing team.
      The analysis used analytical, descriptive and inferential statistics (Chi-square
      test and Fisher's exact test). RESULTS: a total of 3402 procedures of drug
      administrations were observed. Female nursing technicians performed the highest
      number of actions. In none of the procedures did the professional perform all
      necessary actions. 0.2% of drug administrations were preceded by hand hygiene and
      1.3% by disinfection of the multidose vial, ampoule or injectors. CONCLUSION: the
      practice evaluated was classified as undesirable. Failure to achieve the desired
      conformity was probably due to the low adherence of professionals to the practice
      of hand hygiene and disinfection of materials, injectors and connectors.

PMID- 30110094
TI  - Risk factors for fall occurrence in hospitalized adult patients: a case-control
      study.
AB  - OBJECTIVE: to identify risk factors for falls in hospitalized adult patients.
      METHODS: a matched case-control study (one control for each case). A quantitative
      study conducted in clinical and surgical units of a teaching hospital in Southern
      Brazil. The sample comprised 358 patients. Data were collected over 18 months
      between 2013-2014. Data analysis was performed with descriptive statistics and
      conditional logistic regression using Microsoft Excel and SPSS version 18.0.
      RESULTS: risk factors identified were: disorientation/confusion [OR 4.25 (1.99 to
      9.08), p<0.001]; frequent urination [OR 4.50 (1.86 to 10.87), p=0.001]; walking
      limitation [OR 4.34 (2.05 to 9.14), p<0.001]; absence of caregiver [OR 0.37 (0.22
      to 0.63), p<0.001]; postoperative period [OR 0.50 (0.26 to 0.94), p=0.03]; and
      number of medications administered within 72 hours prior the fall [OR 1.20 (1.04
      to 1.39) p=0.01]. CONCLUSION: risk for falls is multifactorial. However,
      understanding these factors provides support to clinical decision-making and
      positively influences patient safety.

PMID- 30110096
TI  - Attitudes towards interprofessional collaboration of Primary Care teams
      participating in the 'More Doctors' (Mais Medicos) program.
AB  - OBJECTIVES: to compare the attitudes regarding interprofessional collaboration of
      health professionals that make up the Family Health Strategy teams participating
      in the 'More Doctors' (Mais Medicos) program; and to identify factors associated
      with attitudes of interprofessional collaboration. METHOD: a descriptive,
      transversal and comparative study developed with 63 health professionals who
      responded to the Jefferson Scale of Attitudes Toward Interprofessional
      Collaboration. The data were statistically analyzed. RESULTS: the sum of the
      scale items ranged from 88 to 139 points. The analysis of all the Family Health
      teams indicated statistically significant differences between the scores of the
      scale and the professional category and between the scores and the education
      level, suggesting that nurses and professionals with higher education are more
      inclined towards collaborative practice. The analysis according to the profile of
      the doctor - Brazilian, Cuban or foreign exchange doctor - found no statistical
      differences regarding the physicians' scores, nor in the scores of the components
      of teams with different profiles. CONCLUSION: the profile did not suggest a
      statistically significant greater or lesser inclination of the doctors or teams
      toward interprofessional work. This study can support new studies which will
      contribute to the analysis of inter-professional collaboration and the impact of
      the Mais Medicos program.

PMID- 30110097
TI  - Syphilis in during pregnancy: association of maternal and perinatal
      characteristics in a region of southern Brazil.
AB  - OBJECTIVE: To analyze the prevalence of syphilis in during pregnancy and its
      association with socioeconomic characteristics, reproductive history, prenatal
      and labor care, and newborn characteristics. METHOD: A retrospective, cross
      sectional study based on gestational and congenital syphilis reports. A (records)
      linkage was performed in the Brazilian databases: "Information System for
      Notifiable Diseases" (Sistema de Informacao de Agravos de Notificacao - SINAN);
      "Live Births Information System" (Sistema de Informacao sobre Nascidos Vivos -
      SINASC); and "Mortality Information System" (Sistema de Informacao sobre
      Mortalidade - SIM). RESULTS: The prevalence of gestational syphilis was 0.57%.
      The following associations of syphilis in pregnancy were found: non-white skin
      color/ethnicity (PR=4.6, CI=3.62-5.76); low educational level (PR=15.4; CI=12.60
      18.86); and absence of prenatal care (PR=7.4, CI=3.68-14.9). The perinatal
      outcomes associated with gestational syphilis were prematurity (PR=1.6 CI=1.17
      2.21) and low birth weight (PR=1.6; CI=1.14-2.28). Two deaths from congenital
      syphilis, one death from another cause and five stillbirths were reported.
      CONCLUSION: The results signify a long way until reaching the World Health
      Organization's goal of eradicating congenital syphilis.

PMID- 30110098
TI  - Cross-cultural validation of the "DISABKIDS" questionnaire for quality of life
      among Colombian children with chronic diseases.
AB  - OBJECTIVE: to describe the cross-cultural validation process of the "DISABKIDS"
      questionnaire in Colombia, for both the children and adolescents' version and the
      parents' version, an instrument intended to measure the health-related quality of
      life of Colombian children and adolescents with chronic diseases. METHOD: the
      cross-cultural validation process was conducted according to an international
      consensual systematic methodology, called standardized linguistic validation, to
      ensure linguistic equivalence with the original questionnaire. RESULTS: the
      pretest's cognitive interviews revealed a need to adjust the questionnaire, which
      consisted of asking for "health condition" rather than only asking for
      "condition". Due to the cultural context, the word "condition" used in the
      original version, when translated to Spanish, refers to socioeconomic conditions
      rather than health conditions. For this reason, 11 items in the children's
      version and eight items in the parents' version were adjusted. CONCLUSIONS: the
      Colombian version of DISABKIDS-37 to measure health-related quality of life among
      children and adolescents with chronic diseases in both the children's and
      parents' versions is equivalent to the original version and is appropriate for
      use in Colombia. Future studies can assess the questionnaire's psychometric
      properties.

PMID- 30110099
TI  - Burnout Syndrome and shift work among the nursing staff.
AB  - OBJECTIVE: to analyze the factors associated with Burnout Syndrome among nursing
      workers according to work shift. METHOD: cross-sectional study addressing a
      representative sample of 502 nursing workers from a philanthropic hospital
      facility. Data were collected using a characterization instrument, the Maslach
      Burnout Inventory - Human Service Survey and the Demand-Control-Support
      Questionnaire. Data were analyzed using descriptive statistics and multiple
      binary logistic regression. RESULTS: levels of Burnout Syndrome were
      significantly higher among those working the day shift and associated factors
      included: high demand; low control; low social support; dissatisfaction with
      sleep and financial resources; being a nurse; and sedentariness. Professionals
      working the night shift, having low social support, being dissatisfied with
      sleep, having children, not having a religion, having worked for a short period
      in the institution, and being a nursing technician or aid were significantly more
      likely to experience high levels of the syndrome. CONCLUSION: psychosocial
      factors and factors from the work context, mainly low social support, were
      associated with the syndrome dimensions among nursing workers of both shifts.

PMID- 30110100
TI  - Alcohol consumption/dependence and resilience in older adults with high blood
      pressure.
AB  - OBJECTIVE: to evaluate alcohol consumption/dependence and resilience in older
      adults with high blood pressure and to analyze the factors associated with these
      variables. METHOD: a descriptive, cross-sectional, quantitative study developed
      with 300 older adult patients with high blood pressure from Family Health
      Strategy units in a municipality of Minas Gerais, Brazil. A semi-structured
      questionnaire called the Alcohol Use Disorder Identification Test and the
      Resilience Scale were used. Data were analyzed using the Pearson's chi-square
      test, Fisher's exact test, Cronbach's alpha, odds ratio and logistic regression.
      RESULTS: 89.3% of the interviewees were low-risk for consuming alcoholic
      beverages. The variables gender, age, smoking and disease duration were
      significantly associated with alcohol consumption/dependence. 36.7% of the people
      presented a low resilience. The variables family and individual monthly income,
      education level, physical activity and leisure had an association with
      resilience. No statistically significant association was observed between alcohol
      consumption/dependence and resilience. CONCLUSION: alcohol consumption and
      resilience can interfere with the physical and mental health of older adults with
      high blood pressure.

PMID- 30110101
TI  - Critical path of women in situations of intimate partner violence.
AB  - OBJECTIVE: To know and analyze the critical path followed by women subjected to
      intimate partner violence until reaching a Reference Center of a Brazilian city,
      from the perspective of these women. METHOD: Qualitative research, based on the
      concept of critical path. Participant observations of the support group of the
      Reference Center and interviews with ten women in situations of violence who were
      followed up in this service. RESULTS: the motivating factors for women to seek
      help were the increase in the severity of the aggressions, the impact of the
      violence on their children and support from their family. They go to several
      sectors and services before reaching the Reference Center, such as the police and
      legal counsel, health and social services. They find little effective responses
      from the services, and care is indicated as the most relevant response factor to
      face the situation. CONCLUSION: the assistance is fragmented and dependent on the
      posture of the professional. The Reference Center is recognized as an important
      place of support for women. In addition to governmental efforts to maintain the
      network structured, the permanent education of the working professionals is also
      fundamental.

PMID- 30110102
TI  - Effectiveness of an Evidence-Based Practice educational intervention with second
      year nursing students.
AB  - OBJECTIVES: to evaluate the effectiveness of an educational intervention on the
      knowledge, skills and attitudes of evidence-based practice among second-year
      nursing students. METHOD: a quasi-experimental before-and-after study. The study
      population consisted of 120 students enrolled in the Nursing Care in Healthcare
      Processes course. The educational intervention was based on theoretical and
      practical classes about the evidence-based practice process and the use of the
      critical incident technique during the clinical clerkship. Effectiveness was
      measured with the Evidence-Based Practice Competence Questionnaire in three
      paired measures using repeated-measures analysis of variance. RESULTS: the mean
      scores of the Evidence-Based Practice Competence Questionnaire were 79.83 (CI 95%
      78.63-81.03) for the basal measurement, 84.53 (CI 95% 83.23-85.83) for the
      intermediate measurement, and 84.91 (CI 95% 83.26-86.55) for the final
      measurement, with a statistically significant difference among the three paired
      measurements (p<0.001). There were statistically significant differences in
      Attitudes (p = 0.034) and Knowledge (p <0.001) but not in Skills (p = 0.137).
      CONCLUSION: this educational intervention based on theoretical and practical
      classes about the evidence-based practice process and the use of the critical
      incident technique during the clinical clerkship enhances evidence-based practice
      competence among second-year nursing degree students.

PMID- 30110103
TI  - The effect of therapeutic listening on anxiety and fear among surgical patients:
      randomized controlled trial.
AB  - OBJECTIVE: To investigate the effect of therapeutic listening on state anxiety
      and surgical fears in preoperative colorectal cancer patients. METHOD: A
      randomized controlled trial with 50 patients randomly allocated in the
      intervention group (therapeutic listening) (n = 25) or in the control group (n =
      25). The study evaluated the changes in the variables state anxiety, surgical
      fears and physiological variables (salivary alpha-amylase, salivary cortisol,
      heart rate, respiratory rate and blood pressure). RESULTS: In the comparison of
      the variables in the control and intervention groups in pre- and post
      intervention, differences between the two periods for the variables cortisol
      (p=0.043), heart rate (p=0.034) and surgical fears (p=0.030) were found in the
      control group, which presented reduction in the values of these variables.
      CONCLUSION: There was no reduction in the levels of the variables state anxiety
      and surgical fears resulting from the therapeutic listening intervention, either
      through the physiological or psychological indicators. However, the contact with
      the researcher during data collection, without stimulus to reflect on the
      situation, may have generated the results of the control group. Clinical Trial
      Registration: NCT02455128.

PMID- 30110105
TI  - Comfort level of caregivers of cancer patients receiving palliative care.
AB  - OBJECTIVE: To verify the association between the level of comfort of the
      caregiver and socio-demographic variables related to caregiving, and the
      patient's functional status and symptoms. METHOD: Cross-sectional study with non
      probabilistic intentional sample. The instruments Palliative Performance Scale
      (score 0 to 100%), Edmonton Symptom Assessment Scale (symptom scores from zero to
      ten) and Holistic Comfort Questionnaire (total score ranging from 49 to 294 and
      mean score from 1 to 6) were used. The relationship between comfort scores and
      independent variables was calculated by multiple linear regression. RESULTS:
      Fifty informal caregivers participated in the study - 80% were female, 32% were
      60 years old or older, 36% were children of the patient, 58% had paid work and
      60% did not have help in the care. The mean overall comfort was 4.52 points. A
      better functional status of the patients was associated with higher levels of
      comfort of the caregivers. Older caregivers who received helped in the care
      activities presented higher comfort scores. CONCLUSION: The level of comfort of
      caregivers of cancer patients receiving palliative care was associated with socio
      demographic variables and patients' functional status and symptoms.

PMID- 30110104
TI  - Social construction of the experience of living with chronic kidney disease.
AB  - OBJECTIVE: To understand the experience of people living with Chronic Kidney
      Disease who have been transplanted, from the meanings constructed based on the
      experienced phenomenon. METHOD: Hermeneutic-phenomenological study based on the
      five lifeworld existentials, according to Van Manen's theoretical framework.
      Eleven transplanted patients participated in the study and data collection was
      carried out through semi-structured interviews, after approval of the study by
      the Ethics Committee of the University of Antioquia. RESULTS: The theme of Living
      with Chronic Kidney Disease emerged, and the subthemes were grouped as lifeworld
      existentials of Temporality: something unexpected, being present and not seeing
      it, being young and sick. Relationality: support, feeling stuck and Terminal
      Chronic Renal Failure. Spatiality: changes in life, sadness and depression.
      Corporeality: body deterioration and changes in sex life. Materiality: effects on
      the economic status. CONCLUSIONS: The care provided to people must be oriented in
      order to recognize their individualities, understanding what the illness means
      for the individual and his family, how they live with it and what the changes
      are, leading them to modify their lives and start a long process, such as living
      with a chronic disease.

PMID- 30110106
TI  - Risks of illness in the work of the nursing team in a psychiatric hospital.
AB  - OBJECTIVE: To analyze the risks of illnesses related to the work context of
      nursing workers in a psychiatric hospital. METHOD: Cross-sectional and
      quantitative study, developed in a psychiatric hospital with 74 nursing workers.
      The Work Context Assessment Scale was used to measure the risks of illness at
      work. Descriptive analyzes were performed with mean and standard deviation. To
      test the reliability of the data, the Cronbach's alpha test was used. The
      correlation between the factors of the work context was tested using the Spearman
      correlation coefficient. RESULTS: The organization of work was considered
      serious, social-professional relationships were considered satisfactory and
      working conditions were considered severe for risks of illness at work. The
      repetitiveness of tasks, work conditions that pose risks to safety, inadequate
      furniture and physical structure of the workplace, and the existence of noise in
      the work environment were indicated as severe risks to workers' health.
      CONCLUSION: The factor working conditions is the one that contributes the most to
      illness among nursing workers.

PMID- 30110108
TI  - Comparative analysis of cognitive-linguistic evaluation in normal hearing
      schoolchildren and users of cochlear implants.
AB  - PURPOSE: When children becom cochlear implant users, they have already had the
      opportunity to develop phonological skills; however, it is possible that they
      miss sound information during speech and, consequently, present difficulties in
      competences associated with the learning of reading and writing. METHODS: The
      study sample consisted of 11 normal hearing children aged 7-10 years and a right
      ear cochlear implant user enrolled in the 3rd grade of Elementary School. The
      Cognitive-Linguistic Assessment protocol was used to evaluate the study
      participants. Data were transcribed and analyzed using descriptive statistics.
      RESULTS: The following sub-tests presented the highest percentage of children
      with superior performance: alphabet in sequence (82%), reading of pseudo-words
      (82%), syllable segmentation (73%), word repetition (82%), copying of shapes
      (72%), and rapid naming (100%).The cochlear implant user presented superior
      performance in all the sub-tests except for word repetition, in which average
      performance was observed. In the rhythm sub-test, none of the normal hearing
      children presented superior performance, and the cochlear implant user performed
      poorly. DISCUSSION: It was possible to observe that the condition of being a
      cochlear implant user is not the only determinant for a child's school failure.
      There are issues that go beyond auditory integrity, because some normal hearing
      children performed poorly in sub-tests such as repetition of pseudo-words,
      rhythm, and alliteration. CONCLUSION: The cochlear implant user presented a
      cognitive-linguistic profile very similar to those of his hearing peers.

PMID- 30110107
TI  - Instruments for the care of pressure injury in pediatrics and hebiatrics: an
      integrative review of the literature.
AB  - OBJECTIVE: to identify existing instruments in the scientific literature about
      the care of pressure injuries in pediatric and hebiatric patients. METHOD: an
      integrative review that selected 32 articles from the PubMed/Medline, LILACS,
      Scopus and CINAHL databases using the descriptors pressure ulcer, decubitus
      ulcer, pediatrics, adolescent and protocols and their equivalent terms in
      Portuguese and Spanish. Inclusion criteria: research articles in full, in
      Portuguese, English or Spanish without any temporal cut-off. The descriptive
      analysis was adopted to categorize the instruments found into the three domains
      of care: evaluative, preventive and curative. RESULTS: 25 instruments for the
      care of pressure injuries in pediatric and hebiatric patients were found, with an
      emphasis on the Braden Q Scale being the most commonly used to assess pressure
      injury risk, and the protocols containing pressure injury staging guidelines
      developed by the National Pressure Ulcer Advisory Panel (NPUAP) and the European
      Pressure Ulcer Advisory Panel (EPUAP). CONCLUSION: the scientific literature has
      valid and reliable instruments that can be used in nursing care practice aimed at
      the evaluative, preventive and curative care of pressure injuries in pediatric
      and hebiatric patients.

PMID- 30110109
TI  - Characterization of communication disorders according to the categories of the
      International Classification of Functioning, Disability and Health - Children and
      Youth (ICF-CY).
AB  - PURPOSE: Characterize the performance of outpatients regarding aspects of
      communication disorders according to the categories of the International
      Classification of Functioning, Disability and Health - Children and Youth Version
      (ICF-CY). METHODS: This is a descriptive, observational study based on a
      retrospective analysis of secondary data collected at a Speech-language Pathology
      outpatient clinic of the public health network, from records of patients aged 5
      16 years, evaluated between 2010 and 2014. Elements of anamnesis and assessment
      reports were analyzed with identification of ICF-CY categories related to the
      following components: Body Functions, Activities and Participation, and
      Environmental Factors. These categories were defined as the study variables,
      stored as categorical variables, and had their frequency distribution
      investigated by descriptive statistical analysis. RESULTS: One hundred eighty
      medical records were included in the study, and 65 of the 168 pre-selected
      categories were identified. As for the component Body Functions, 13 items were
      verified, with the category related to impairment in Mental functions of language
      as the most frequently mentioned. Of the 34 categories identified in the
      component Activities and Participation, Learning to read - Performance and Doing
      housework - Performance were the ones that most frequently presented
      difficulties. Of the 18 categories of the component Environmental Factors, the
      one described in most reports as Barrier was Individual attitudes of
      acquaintances, peers, colleagues, neighbors, and community members. CONCLUSION:
      Changes were found in categories of the three components of the ICF-CY analyzed,
      indicating the existence of issues that affected the functional performance
      regarding aspects of communication disorders of children and adolescents assisted
      at an outpatient environment.

PMID- 30110111
TI  - EVALUATION OF NUTRITIONAL STATUS IN PATIENTS WITH CYSTIC FIBROSIS ACCORDING TO
      AGE GROUP.
AB  - OBJECTIVE: To evaluate the nutritional profile of the population assisted at a
      reference center for cystic fibrosis treatment. METHODS: Cross-sectional study
      including patients with cystic fibrosis assisted at a pediatric reference center
      in Sao Paulo, Brazil, in 2014. All patients attending regular visits who agreed
      to participate in the study were included. A questionnaire on dietary habits (24
      hour diet recall) and socioeconomic characteristics was applied. Anthropometric
      data (compared with the reference from the World Health Organization, 2006 and
      2007) and pulmonary function data were collected from medical records. Patients
      were stratified into age groups for statistical analysis. RESULTS: A total of 101
      patients were included in the study (59.4% male, 86.4% Caucasian), with median
      age of 10 years old. Most patients (n=77; 75%) were classified as eutrophic, but
      lower values of body mass index (BMI) Z scores were observed in schoolchildren
      and adolescents. The proportion of underweight patients was 10% (n=2) among
      preschoolers and 35% (n=6) of the school age group. Dietary intake was adequate,
      and the use of only two supplements (medium chain triglycerides and complete
      powdered supplement) was associated with adequacy of macronutrient intake. The
      socioeconomic characteristics did not show any statistical association with the
      nutritional state or nutritional consumption. Lung function was not significantly
      different between neither adolescents nor individuals with worse nutritional
      status in this sample. CONCLUSIONS: Most of the patients presented adequate
      nutritional status and adequate consumption of calories and macronutrients,
      indicating appropriate nutritional management. New studies focusing on preschool
      children should be performed to assess if it is possible to reduce the
      nutritional risk of patients with cystic fibrosis at older ages.

PMID- 30110110
TI  - ERRATUM.
AB  - [This corrects the article doi: 10.1590/1984-0462/;2018;36;2;00011] [This
      corrects the article doi: 10.1590/1984-0462/;2018;36;2;00016].

PMID- 30110112
TI  - PERCEPTIONS ON THE IMPORTANCE OF VACCINATION AND VACCINE REFUSAL IN A MEDICAL
      SCHOOL.
AB  - OBJECTIVE: To identify the perception of medical students and physicians on the
      importance of vaccination and the risks of vaccine refusal. METHODS: Cross
      sectional study with application of questionnaires about vaccines, vaccine
      refusal and its repercussions on public and individual health. A sample of 92
      subjects was selected from a private medical school: group 1 (53 students from
      first to fourth grades) and group 2 (39 physicians). Data collected were
      tabulated in the Microsoft Excel Program and analyzed by Fisher's exact test.
      RESULTS: Both groups considered the National Immunization Program reliable and
      recognized the importance of vaccines, but 64.2% of students and 38.5% of
      physicians are unaware of the vaccine-preventable infectious diseases in the
      basic immunization schedule. Most of the interviewees had a personal vaccine
      registry, but not all had received the 2015 influenza vaccine. Both groups had
      known people who refused vaccines for themselves or for their children
      (respectively, 54.7 and 43.3% of students and 59.0 and 41.0% of physicians). The
      total of 48.7% of physicians had already assisted vaccine refusers. Appointed
      causes of vaccine refusal were: fear of adverse events, philosophical and
      religious reasons and lack of knowledge about severity and frequency of diseases.
      Ethical aspects of vaccine refusal and legal possibilities of vaccine
      requirements for children are not consensus. CONCLUSIONS: Medical students and
      doctors are not adequately vaccinated and have queries about the vaccination
      schedule, vaccine safety and vaccine refusal. Improving these professionals'
      knowledge is an important strategy to maintain vaccine coverage and address
      vaccine refusal ethically.

PMID- 30110113
TI  - SENSORY CHANGES IN MOUTH BREATHERS: SYSTEMATIC REVIEW BASED ON THE PRISMA METHOD.
AB  - OBJECTIVE: To review, in the literature, information regarding changes in the
      sensory systems of mouth breathers. DATA SOURCES: The search was conducted in the
      following databases PubMed, BIREME, LILACS, Web of Science and Scopus. The search
      was independently carried out by two researchers, following the selection
      criteria. Original articles that approached mouth breathing and changes in
      sensory systems published in Portuguese, English and Spanish were published.
      Literature review of articles, dissertations, book chapters, case studies and
      editorials were excluded. DATA SYNTHESIS: We found 719 articles. Among them, 663
      were excluded by the title and 22 by the summary. Among the 34 analyzed
      manuscripts, 23 were repeated and 8 were excluded by reading the full text. Thus,
      3 articles were selected for this review. CONCLUSIONS: Most studies presents the
      occurrence of changes in sensory systems in mouth breathing children. However,
      sensory reception is a matter of more concern. Besides, the evaluation of sensory
      systems was not standardized, which may have led to less precise results in the
      studied population.

PMID- 30110114
TI  - EFFECTIVENESS OF OBESITY INTERVENTION PROGRAMS BASED ON GUIDELINES FOR ADOLESCENT
      STUDENTS: SYSTEMATIC REVIEW.
AB  - OBJECTIVE: To verify the effectiveness of educational interventions based on
      guidance on physical activity and nutrition in schoolchildren. DATA SOURCES: A
      systematic search was carried out in four electronic databases containing
      articles published between October 2007 and January 2017 and addressing
      educational interventions with emphasis on both nutritional education and
      physical activity in schoolchildren and adolescents aged 10 to 19 years. DATA
      SYNTHESIS: Twelve articles were selected for this review, of which four included
      only educational interventions; four made and association between educational
      interventions, inclusion of healthy foods and physical activity; two made a
      relation between guidelines and physical activity; and finally, two associated
      guidelines with consumption of healthy foods. CONCLUSIONS: Interventions based on
      physical activity and/or nutrition counseling were efficient and showed superior
      results in studies that associated the practice of physical activity with
      counseling. However, the need for new studies on educational interventions among
      schoolchildren and adolescents was made evident.

PMID- 30110116
TI  - Efficacy and safety of intravenous chemotherapy during intensive treatment phase
      in patients with newly diagnosed pulmonary tuberculosis.
AB  - : The purpose of our study was to examine the efficacy and safety of intravenous
      chemotherapy during intensive treatment phase for patients with newly diagnosed
      pulmonary tuberculosis (pulmonary TB). MATERIALS AND METHODS: The study involved
      92 patients with newly diagnosed pulmonary TB aged between 20 years and 68 years.
      All patient with newly diagnosed pulmonary TB and chemosensitive tuberculosis
      were enrolled in this study. The patients were allocated to two groups. The first
      (control) group of 46 patients received standard chemotherapy orally. The second
      (main) group consisted of 46 patients who were prescribed isoniazid, rifampin,
      ethambutol by i / v transfusion, and pyrazinamide orally as a part of the
      standard treatment. RESULTS: Symptoms of intoxication in pulmonary TB patients
      from the second group were eliminated faster (1.42+/-0.35) of a month than the
      same symptoms of the group 1-(2.96+/-0.24) of the months,p < 0.05; disappearance
      of respiratory symptoms of the group 2-(1.34+/-0.29) of a month, group 1-(2.65+/
      0.43) of the months,p < 0.05. In the group 2, the bacterioexcretion time was
      reducing faster and up to 2 months it reached 37(80.43+/-5.85%) while the time
      for the control group reached 25(54.35+/-7.34%),p < 0.05. Destruction healing and
      healing frequency of destruction cavities up to 4 months amounted to 38(82.61+/
      5.59%) (in control group - 28(60.87+/-7.20%),p < 0.05) and residual changes were
      reducing (small changes or absence of even minimal radiological changes were
      found in 29(63.04 +/-7.12%) patients versus 18(39.13+/-7.20%) of the group 1, and
      large residual changes accordingly in 17(36.96+/-7.12%) and 28(60.87+/-7.20%),p <
      0.05. CONCLUSIONS: Thanks to i/v chemotherapy clinical manifestations of the in
      patients with pulmonary TB were eliminated faster, severe side effects to anti-TB
      drugs were not noticed, time of bacterial excretion and healing destruction
      reduced, healing frequency of destruction cavities increased and the residual
      changes decreased.

PMID- 30110117
TI  - The Prevalence and Predicting Factors of Pulmonary Thromboembolism in Patients
      with Exacerbated Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND AND AIMS: The risk of pulmonary thromboembolism (PTE) in patients with
      exacerbated chronic obstructive pulmonary disease (e-COPD) is higher than in non
      COPD states. This study aimed to evaluate the prevalence and the parameters that
      are critical for finding the incidence of PTE in patients with e-COPD. METHODS:
      This cross-sectional study was performed on 68 consecutive patients with the e
      COPD, referred to the Pulmonary Disease Department at the Shariati Hospital in
      Tehran between 2013 and 2014. In addition to collecting data on the history of
      disease and physical examination, arterial blood sampling, spirometry,
      electrocardiography and echocardiography were performed for all patients. All
      patients underwent the computed the tomography pulmonary angiography (CT-PA) as a
      method of choice for diagnosing PTE. RESULTS: Out of 68 cases (7.4%), five were
      had CT angiography findings suggesting PTE. These patients were all male and had
      a higher mean age (79 vs. 65 years), lower mean systolic blood pressure (88.36
      vs. 118.33 mmHg), and a higher mean heart rate (133.12 vs 90.33 beats/min),
      compared to e-COPD patients without PTE. Arterial blood gas analysis in patients
      with PTE demonstrated a lower HC03 (2.33 vs. 9.44 mEq/l) and PC02 (44.35 vs.
      51.43 mmHg) levels. The mean LVEF was lower in patients with PTE (34.14 +/-4.49%
      vs. 46.94 +/- 8.27%). CONCLUSION: The prevalence of PTE in our series of patients
      with e-COPD was 7.4%. According to the study results, male gender, advanced age,
      hypotension, tachycardia, and respiratory alkalosis are factors indicating
      possible PTE among patients with e-COPD.

PMID- 30110115
TI  - Sickness absence after carpal tunnel release: a systematic review of the
      literature.
AB  - Objectives The aim of this systematic review was to provide an overview of time
      to return to work (RTW) after carpal tunnel release (CTR), including return to
      different occupations and working patterns. Methods A systematic search from
      inception to 2016 was conducted using nine electronic databases, trial registries
      and grey literature repositories. Randomized controlled trials and observational
      studies reporting RTW times after CTR were included. Study risk of bias was
      assessed using Cochrane risk of bias assessment tools. Time to RTW was summarized
      using median and range. Results A total of 56 relevant studies were identified:
      18 randomized controlled trials and 38 observational studies. Only 4 studies were
      rated as having a low risk of bias. Reported RTW times ranged from 4-168 days.
      Few studies reported occupational information. Among 6 studies, median time to
      return to non-manual work was 21 days (range 7-41), compared with 39 days for
      manual work (range 18-101). Median time to return to modified or full duties was
      23 days (ranges 12-50 and 17-64, respectively), as reported by 3 studies. There
      was no common method of defining, collecting or reporting RTW data. Conclusions
      This review highlights wide variation in reported RTW times after CTR. Whilst
      occupational factors may play a role, these were poorly reported, and there is
      currently limited evidence to inform individual patients of their expected
      duration of work absence after CTR. A standardized definition of RTW is needed,
      as well as an agreed method of collecting and reporting related data.

PMID- 30110118
TI  - Study of Pulmonary function tests in Type 2 Diabetes Mellitus and their
      correlation with glycemic control and systemic inflammation.
AB  - Background - Reduced lung function in diabetes has been described for long but
      its clinical importance is not yet clear. Also, limited literature is available
      regarding its association with sugar control, and its correlation with
      inflammatory markers. Thus, we aimed to study the pulmonary function test
      abnormalities and systemic inflammation in type 2 diabetes mellitus. Methods 100
      patients of type 2 diabetes were divided into two groups depending on control of
      diabetes (group A-HbA1C<=7% and group B-HbA1C >7%). All the subjects selected
      underwent detailed evaluation including testing for HbA1C, HsCRP (high
      sensitivity C-reactive protein), serum ferritin and serum fibrinogen, along with
      pulmonary function testing. Results Percentage predicted FVC (forced vital
      capacity), FEV1 (forced expiratory volume in 1 second) and SVC (slow vital
      capacity) were significantly reduced, while mean values of inflammatory markers
      [fibrinogen (p <0.001) and hsCRP (p 0.002)] were significantly higher in
      uncontrolled diabetes group. There was a significant negative correlation between
      FEV1 (r = -0.739, p<0.001), FVC ( r = -0.370, p<0.001), SVC (r = -0.635, p<
      0.001) with HbA1C. HbA1C had a positive correlation with hsCRP (r = -0.308, p
      0.002) and fibrinogen (r = 0.388 ,p 0.001). Conclusion Pulmonary functions were
      decreased and inflammatory markers like hsCRP, fibrinogen, and ferritin
      significantly increased in uncontrolled diabetics. Also, a potential association
      was seen between higher values of inflammatory markers like hsCRP and fibrinogen
      and decrease in lung function. This information, requiring confirmation with
      larger multicentre studies, remains important because of potential
      epidemiological, clinical and therapeutic implications.

PMID- 30110119
TI  - Intrapericardial cisplatin combined with oral colchicine resulted in long term
      control of malignant pericardial effusion in the course of metastatic renal
      cancer.
AB  - Background Neoplastic pericardial effusion (NPE) represents a common cause of
      morbidity and mortality in patient with cancer. NPE presents frequently as
      cardiac tamponade, requiring urgent pericardiocentesis or pericardiotomy, with
      subsequent pericardial fluid drainage. Despite high effectiveness of such
      procedures, the recurrence of effusion is noted in 30- 60% of patients.
      Intrapericardial therapy with cisplatin was found to be effective in NPE due to
      lung and breast cancer. Its role in cardiac tamponade due to renal cancer is
      unknown. Case presentation We presented 82-year-old man with renal cancer who was
      admitted to the Intensive Care Unit because of threatening pericardial tamponade
      due to NPE . Urgent subxiphoid pericardiotomy was performed with subsequent
      evacuation of 1000ml of bloody fluid. On the inner surface of the pericardium
      several pink nodules were found. Histological examination revealed carcinoma
      clarocellulare. In view of the persistent high drainage of the pericardium,
      intrapericardial cisplatin therapy was performed. The first day after surgery
      colchicine 0.5 mg/day/po was also introduced. No side effects of this treatment
      were observed. The patient died 12- month later due to cancer progression and
      cachexia. No recurrence of pericardial effusion was observed. Conclusion This is
      the first case study demonstrating long-term efficacy and safety of
      intrapericardial cisplatin combined with oral colchicine in NPE due to metastatic
      renal cell carcinoma.

PMID- 30110120
TI  - 2-year follow-up of Lung transplantation as a treatment of Hereditary hemorrhagic
      telangiectasia (Osler-Weber-Rendu disease) - a case report.
AB  - : Hemorrhagic telangiectasia (HHT) is a disease of initially mild course -
      manifesting with recurrent nosebleeds and increased fatigue. Nevertheless, its
      progression can deteriorate patient's health. Solid organ transplantation becomes
      the only therapeutic option to save a life. Case series describes 19 years old
      female patient, who was diagnosed with HHT and qualified for lung
      transplantation. She meets Curacao criteria for HHT (3/4). Her health
      deteriorated significantly to the point of the referral to Covered for Blind
      Review. Due to her condition she was qualified for lung transplantation as one
      diagnosed with Pulmonary arteriovenous malformations and then transplanted at the
      age of 17. Direct postoperative period was complicated by HSV2 infection of the
      wound. 18 months after the procedure, patient underwent acute cholangitis.
      Presence of portal and systemic fistulas was noted and the final diagnosis of HHT
      was made. Despite the fact that proper diagnosis was made posttransplant, it was
      a good treatment. The patient is currently 2 years after the lung transplant and
      feels good. DISCUSSION: Lung transplantation is a viable therapeutic option for
      patients with HHT, as there are reports of other patients, who have benefited
      from lung transplantation after other therapeutic options were exhausted.

PMID- 30110122
TI  - Pleiotropic effect of vitamin D in cystic fibrosis.
AB  - Cystic fibrosis - CF - is the most common recessively autosomally and inherited
      disorder in the Caucasian population. It is incurable, multi-systemic disease
      with progressive course. CF is caused by CFTR gene mutation, the product of which
      is Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). CF patients are
      exposed to fat-soluble vitamins deficiency, including vitamin D. It is due to the
      fat malabsorption (caused by exacerbation exocrine pancreatic insufficiency),
      decreased sun exposure (caused by receiving antibiotics photophobia), reduction
      of adipose tissue and insufficient supply with food. The discovery of vitamin D
      receptor (VDR) presence outside the skeletal system allowed to conclude, that
      vitamin D is responsible not only for mineral economy, but also for immunological
      processes, respiratory status, intestial microflora and cystic fibrosis - related
      diabetes (CFRD) course. Based on literature data, it is suggested that vitamin D
      plays an important role in the prevention of diseases coexisting with CF. The
      right dosage of vitamin D allows to maintain a better lung function and prevent
      chronic pulmonary infections. It has also been shown that normal levels of
      vitamin D may be important in increasing the chances of successful lung
      transplant surgery. Taking the wide spectrum of vitamin D effect into account, it
      is recommended to maintain serum concentrations above the minimum in patients
      with CF. In summary, maintaining the proper vitamin D levels in patients with CF
      is important because of its pleiotropic effect. It can be achieved through
      regular monitoring of vitamin D levels and individual supplementary dose for each
      patients.

PMID- 30110121
TI  - Neprilysin inhibitors as a new approach in the treatment of right heart failure
      in the course of chronic obstructive pulmonary disease.
AB  - The aim of the study was to find out scientific evidence on the possible use of
      the combined angiotensin II receptor antagonist and neprilysin inhibitors (ARNI)
      in patients with right heart failure (RHF) in the course of chronic obstructive
      pulmonary disease (COPD). It has been proven that a lack of neprilysin or its
      reduced expression in hypoxia leads to exacerbation of pulmonary arterial
      remodelling (PAR) or pulmonary hypertension (PH) in the mechanism related to the
      platelet-derived growth factor (PDGF) resulting in the proliferation and
      migration of pulmonary artery smooth muscle cells and endothelial-to-mesenchymal
      transition. Such action in the course of COPD can lead to RHF, which would
      signify noxious effect of this group of drugs. However, the inhibition of
      neprilysin also inhibits natriuretic peptide metabolism. The representative of
      this group - brain natriuretic peptide (BNP) - acts as a vasodilator and also
      exerts an anti-proliferative activity through the cGMP-dependent protein kinase G
      pathway. Additionally, it causes bronchodilation by inducing the release of
      acetylcholine from bronchial epithelial cells. This suggests that natriuretic
      peptides may appear to be a potential treatment agent in patients with cardiac
      complications and COPD. Their effects associated with the immunosuppression
      capacity by reducing the release of inflammatory mediators - IL-6, IL-1beta, and
      TNF-alpha can bring benefits to patients with acute lung injury caused by
      pulmonary inflammation during COPD exacerbations. Considering the potentially
      positive effect of natriuretic peptides in this group of patients, further
      research is required in this area, which can provide strong scientific data
      demonstrating the need for introducing ARNI drugs to the treatment of patients
      with COPD.

PMID- 30110123
TI  - Antiretroviral considerations in HIV-infected patients undergoing bariatric
      surgery.
AB  - WHAT IS KNOWN AND OBJECTIVE: With the advent of antiretroviral therapy and the
      resultant decrease in mortality among adults living with human immunodeficiency
      virus (HIV), there is now an increased incidence of obesity and obesity-related
      comorbidities in these patients. Bariatric surgery is becoming an increasingly
      common treatment option for patients who are classified as clinically obese.
      There are limited data regarding the use of antiretroviral therapy in patients
      who have undergone bariatric surgery. The purpose of this review was to evaluate
      the available literature regarding antiretroviral therapy and pharmaceutical
      properties in this special population. METHODS: Literature review was performed
      through PubMed, utilizing search terms of bariatric surgery, sleeve gastrectomy,
      Roux-en-Y, HIV infection, obesity and antiretroviral. Direct medical information
      requests to antiretroviral pharmaceutical manufacturers were also completed.
      RESULTS: Several case series and case reports have been published which
      demonstrate minimal risk of complications and maintenance of virologic
      suppression in the vast majority of patients. Bariatric surgery appears to be an
      effective mechanism for assistance in controlling obesity in patients infected
      with HIV; however, numerous factors may impact the safe and effective use of
      antiretroviral therapy. WHAT IS NEW AND CONCLUSION: Due to the physiologic
      changes and postoperative management following bariatric surgery, evaluation of
      the patients' medication regimens must be considered and several factors should
      be taken into account when choosing the appropriate antiretroviral regimen for
      these patients. Furthermore, communication between the patients' surgeon, HIV
      provider and a clinical pharmacist should occur prior to surgery to ensure the
      patient is optimized to achieve the best outcome including maintaining virologic
      suppression.

PMID- 30110124
TI  - Antihypertensive drugs and prostate cancer survival after radical prostatectomy
      in Finland-A nationwide cohort study.
AB  - Antihypertensive (anti-HT) drugs targeting renin-angiotensin-aldosterone (RAA)-
      system have been associated with improved prostate cancer (PCa)-specific
      survival. Challenge is that often multiple drugs are used simultaneously. We
      evaluated the association between use of anti-HT drugs and PCa survival among
      14,422 surgically treated Finnish PCa patients. Information on drug purchases was
      obtained from a national prescription database. We used Cox regression to
      calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of
      PCa death and initiation of androgen deprivation therapy (ADT) with adjustment
      for age, tumor extent, use of statins and for Charlson Comorbidity Index.
      Angiotensin-converting enzyme (ACE)- inhibitors, angiotensin- receptor (ATR)
      blockers, diuretics, calcium-channel blockers, beta-blockers and other anti-HT
      drugs were analyzed as separate time-dependent variables to model simultaneous
      use. Overall anti-HT drugs were associated with an increased risk of PCa death.
      Conversely use of ATR-blockers was associated with decreased risk of PCa death
      (HR: 0.43, 95% CI: 0.26-0.72 and HR: 0.60, 95% CI 0.37-0.97 for pre- and post
      diagnostic use). Similar risk decrease was not observed in other drug groups.
      Anti-HT drugs were also associated with an increased risk of starting ADT, with
      the exception of ATR-blockers (HR: 0.81 CI:0.71-0.92). ATR- blockers differ from
      other anti-HT drugs as the survival is better in users of this drug group. The
      result partly supports the role of RAA system in PCa progression. Nevertheless,
      the risk decrease was not observed in ACE-inhibitor users. Further research is
      needed to elucidate the molecular mechanism for the potential anticancer effect
      of ATR- blockers.

PMID- 30110125
TI  - CYPOR is a novel and independent prognostic biomarker of recurrence-free survival
      in triple-negative breast cancer patients.
AB  - Prognostic and predictive biomarkers of disease and treatment outcome are needed
      to ensure optimal treatment of patients with triple-negative breast cancer
      (TNBC). In a mass spectrometry-based global proteomic study of 44 formalin-fixed,
      paraffin-embedded (FFPE) primary TNBC tumors and 10 corresponding metastases, we
      found that Cytochrome P450 reductase (CYPOR) expression correlated with patient
      outcome. The correlation between CYPOR expression and outcome was further
      evaluated in a Danish cohort of 113 TNBC patients using immunohistochemistry and
      publicly available gene expression data from two cohorts of TNBC and basal-like
      breast cancer patients, respectively (N = 249 and N = 580). A significant
      correlation between high CYPOR gene expression and shorter recurrence-free
      survival (RFS), but not overall survival, was found in the cohort of 249 TNBC
      patients (p = 0.018, HR = 1.77, 95% CI 1.1-2.85), and this correlation was
      recapitulated in a cohort of 580 basal-like breast cancer patients (p = 0.018, HR
      = 1.4, 95% CI 1.06-1.86). High CYPOR protein expression was also associated with
      shorter RFS in the cohort of 113 TNBC patients (p = 0.017, HR = 2.73, 95% CI 1.20
      6.19), particularly those who were lymph node tumor-negative (p = 0.029, HR =
      5.22). Multivariate Cox regression analysis identified CYPOR as an independent
      prognostic factor for shorter RFS in TNBC patients (p = 0.032, HR = 2.19, 95% CI
      1.07-4.47). Together, these data suggest high expression of CYPOR as an
      independent prognostic biomarker of shorter RFS, which could be used to identify
      patients who should receive more extensive adjuvant treatment and more aggressive
      surveillance.

PMID- 30110126
TI  - Toxic dinoflagellates produce true grazer deterrents.
AB  - Many phytoplankton species produce toxic substances, but their functional role is
      unclear. Specifically, it remains uncertain whether these compounds have a toxic
      or deterrent effect on grazers; only, the latter is consistent with toxins as
      defensive tools. Here, we show that 10 of 12 species or strains of toxic
      dinoflagellates were consumed at lower rates than a similarly sized nontoxic
      dinoflagellate by a copepod. Through video observations of individual prey-grazer
      interactions, we further demonstrate that the dominating mechanism is through
      capture, examination, and subsequent rejection of vital cells, that is, a true
      deterrent effect that offers a straightforward explanation to its evolution. We
      argue that the diversity of grazer responses to toxic phytoplankton reported in
      the literature, including toxic effects, and the high diversity of toxin profiles
      between strains of the same phytoplankton species reflect different stages of an
      ever-ongoing evolutionary arms race, facilitated by rapid adaptation of grazers
      to toxic substances. We further argue that defensive toxicity requires a chemical
      signal exterior to the cell that informs the grazer about the toxicity of the
      cell. The signal can be the toxin itself or just an aposematic signal of
      toxicity. In the former case, allelochemical effects may emerge at high cell
      concentrations as a nonadaptive side effect of a predator defenses.

PMID- 30110127
TI  - Extracellular vesicles from human liver stem cells inhibit tumor angiogenesis.
AB  - Human liver stem-like cells (HLSC) and derived extracellular vesicles (EVs) were
      previously shown to exhibit anti-tumor activity. In our study, we investigated
      whether HLSC-derived EVs (HLSC-EVs) were able to inhibit tumor angiogenesis in
      vitro and in vivo, in comparison with EVs derived from mesenchymal stem cells
      (MSC-EVs). The results obtained indicated that HLSC-EVs, but not MSC-EVs,
      inhibited the angiogenic properties of tumor-derived endothelial cells (TEC) both
      in vitro and in vivo in a model of subcutaneous implantation in Matrigel.
      Treatment of TEC with HLSC-EVs led to the down-regulation of pro-angiogenic
      genes. Since HLSC-EVs carry a specific set of microRNAs (miRNAs) that could
      target these genes, we investigated their potential role by transfecting TEC with
      HLSC-EV specific miRNAs. We observed that four miRNAs, namely miR-15a, miR-181b,
      miR-320c and miR-874, significantly inhibited the angiogenic properties of TEC in
      vitro, and decreased the expression of some predicted target genes (ITGB3, FGF1,
      EPHB4 and PLAU). In parallel, TEC treated with HLSC-EVs significantly enhanced
      expression of miR-15a, miR-181b, miR-320c and miR-874 associated with the down
      regulation of FGF1 and PLAU. In summary, HLSC-EVs possess an anti-tumorigenic
      effect, based on their ability to inhibit tumor angiogenesis.

PMID- 30110128
TI  - An Asymmetric Anion-Pillared Metal-Organic Framework as a Multisite Adsorbent
      Enables Simultaneous Removal of Propyne and Propadiene from Propylene.
AB  - The one-step removal of multi-component gases based on a single material will
      significantly improve the efficiency of separation processes but it is
      challenging, owing to the difficulty to precisely fabricate porous materials with
      multiple binding sites tailored for different guest molecules. Now a niobium
      oxide-fluoride anion-pillared interpenetrated material ZU-62 (NbOFFIVE-2-Cu-i,
      NbOFFIVE=NbOF52- ) is presented. It features asymmetric O/F node coordination for
      the simultaneous removal of trace propyne and propadiene from propylene. The
      narrow distribution nanospace (aperture of Site I 6.75 A, Site II 6.94 A, Site
      III 7.20 A) derived from the special coordination geometry within ZU-62
      customized the corresponding energy-favorable binding sites for the propyne and
      propadiene that enable propadiene uptake (1.74 mmol g-1 ) as well as excellent
      propyne uptake (1.87 mmol g-1 ) under ultra-low pressure (5000 ppm). The
      multisite capture mechanism was revealed by modeling studies.

PMID- 30110129
TI  - Conjugated Polymer Nanoparticles with Appended Photo-Responsive Units for
      Controlled Drug Delivery, Release, and Imaging.
AB  - Carriers that can afford tunable physical and structural changes are envisioned
      to address critical issues in controlled drug delivery applications. Herein,
      photo-responsive conjugated polymer nanoparticles (CPNs) functionalized with
      donor-acceptor Stenhouse adduct (DASA) and folic acid units for controlled drug
      delivery and imaging are reported. Upon visible-light (lambda=550 nm)
      irradiation, CPNs simultaneously undergo structure, color, and polarity changes
      that release encapsulated drugs into the cells. The backbone of CPNs favors FRET
      to DASA units boosting their fluorescence. Notably, drug-loaded CPNs exhibit
      excellent biocompatibility in the dark, indicating perfect control of the light
      trigger over drug release. Delivery of both hydrophilic and hydrophobic drugs
      with good loading efficiency was demonstrated. This strategy enables remotely
      controlled drug delivery with visible-light irradiation, which sets an example
      for designing delivery vehicles for non-invasive therapeutics.

PMID- 30110131
TI  - Effects of titanium oxide surface properties on bone-forming and soft tissue
      forming cells.
AB  - BACKGROUND: Previous studies have concluded that certain titanium oxide (TiO2 )
      surface properties promote bone-forming cell attachment. However, no
      comprehensive studies have investigated the effects of TiO2 surface and film
      morphology on hard and soft tissues. PURPOSE: The aim of this study is to
      understand the effects of TiO2 morphology on the proliferation and
      differentiation of murine preosteoblasts (MC3T3-E1) and proliferation of human
      gingival fibroblasts (HGF-1) using in vitro experiments. MATERIALS AND METHODS:
      Samples were fabricated with several TiO2 thickness and crystalline structure to
      mimic various dental implant surfaces. in vitro analysis was performed for 1, 3,
      and 7 days on these samples to assess the viability of MC3T3-E1 and HGF-1 cells
      in contact with the modified oxide surfaces. RESULTS: Results showed that HGF-1
      cells exhibited no significant difference in viability on modified oxide surfaces
      versus a titanium control across experiments. MC3T3-E1 cells exhibited a
      significantly higher viability for the modified oxide surface in 1 day
      experiments, but not in 3 or 7 day experiments. Alkaline phosphatase expression
      in MC3T3-E1 was not significantly different on modified oxide surfaces versus the
      control across all experiments. A slight positive trend in viability was observed
      for cells in contact with rougher modified oxide surfaces versus a titanium
      control in both cell types. CONCLUSIONS: These observations suggest that
      crystallinity and thickness do not affect the long-term viability of hard or soft
      tissue cells when compared to a cpTi surface. Therefore, treatments like
      anodization on implant components may not directly affect the attachment of hard
      or soft tissue cells in vivo.

PMID- 30110130
TI  - Calibration-free quantitative immunoassay by flow cytometry: Theoretical
      consideration and practical implementation for IgG antibody binding to CD14
      receptors on human leukocytes.
AB  - We propose a calibration-free method to determine the number of receptors per
      cell, as well as the direct and the reverse reaction rate constants for a single
      receptor. The method is based on the analysis of the temporal evolution of the
      cells mean fluorescent intensity measured by a flow cytometer during the ligand
      receptor (antigen-antibody) binding under the conditions of their comparable
      concentrations. We developed the kinetic approach accounting both for the delay
      between the dilution and the measurement and for the practical duration of the
      measurement itself. The method was applied to determine thenumber of CD14
      receptors on human blood mononuclear (granulocytes, monocytes, lymphocytes) cells
      of several donors. We also obtained the direct ( k+= (5.6 +/- 0.2) * 107 M-1 min
      1 ) and reverse ( k-= (1.3 +/- 0.2) * 10-2 min-1 ) rate constants of ligand
      receptor interaction, and estimated the size of the binding site as b = 0.5 nm.
      The latter allows one to recalculate the rate constants for a different ligand,
      fluorescent label, medium viscosity, and/or temperature. The knowledge of the
      rate constants is essential for the calibration-free determination of the number
      of receptors per cell from a single kinetic curve of the cells mean fluorescence
      intensity.

PMID- 30110132
TI  - Short-term report of an ongoing prospective cohort study evaluating the outcome
      of full-arch implant-supported fixed hybrid polyetheretherketone-acrylic resin
      prostheses and the All-on-Four concept.
AB  - BACKGROUND: More research is needed on the study of new materials for fixed
      prosthetic implant-supported rehabilitations. PURPOSE: The purpose of this study
      was to report the short-term outcome of full-arch implant-supported fixed hybrid
      polyetheretherketone (PEEK)-acrylic resin prostheses and the all-on-four concept.
      MATERIALS AND METHODS: This prospective cohort clinical study included 37
      patients (29 women, eight men) with an average age of 60 years (range: 38-78
      years) with 49 full-arch hybrid PEEK-acrylic resin prosthesis supported by
      implants through the all-on-four concept. Primary outcome measures were
      prosthetic survival. RESULTS: Two patients with two maxillary prostheses were
      lost to follow-up. One patient with a double full-arch rehabilitation fractured
      the mandibular PEEK framework, rendering a 98% prosthetic survival rate. No
      implants were lost. The average (SD) marginal bone remodeling after 1 year of
      follow-up was 0.37 mm (0.58 mm). Technical complications concerning the veneer
      adhesion occurred in six patients and were resolved in all patients (with
      exception of the patient with prosthetic failure) through the creation of
      mechanical retentions and changing the bonding primer. Mechanical complications
      occurred in three patients and five prostheses consisting in prosthetic screw
      loosening (n = 2 patients) and fracture of the acrylic resin teeth (the patient
      with a prosthetic failure). CONCLUSIONS: Within the limitations of this study,
      the results suggest that hybrid polymer (PEEK)-acrylic resin prostheses supported
      by implants for full-arch rehabilitation may represent a valid treatment option,
      still requiring longer-term validation.

PMID- 30110133
TI  - Flow cytometry in formamide treated cells.
AB  - The use of formamide for the study in flow cytometry of cell cycle phases, by DNA
      content measurement in human cancer cell lines, was recently published. In this
      manuscript, we verify the possibility of extending the procedure to simultaneous
      analysis of other parameters. The results obtained, here reported, show that the
      treatment of samples by formamide is compatible with the simultaneous detection
      of DNA content and surface phenotypes, with quantification of replicating DNA and
      with measurement of cells with fractional content of DNA. For each of these three
      applications, we have adapted the procedure to gain simple, reproducible and
      above all advantageous protocols. Regarding the simultaneous analysis of DNA
      content and phenotyping the use of formamide achieves optimal DNA stoichiometric
      staining (C.V. < 3; G2/G1 ratio = 2 +/- 0.05) and sufficient maintenance of
      physical parameters and membrane fluorescence. In the study of duplicating DNA
      labeled with click chemistry, our procedure eliminates paraformaldehyde (PFA)
      fixation improving the DNA stoichiometric staining and allows the use of 7
      aminoactinomycin D (7-AAD) preserving the Alexa Fluor 488 quantum efficiency.
      Concerning the detection of cells with fractional content of DNA,
      permeabilization and fixation by formamide gives the advantage of resolve on
      linear scale sub-G1 cells from debris and to allow optimal sample recovery (>90%)
      which is essential in the study of cell necrobiology. Cells treatment by
      formamide, suitably modified for different applications, can be used to prepare
      cell samples for flow cytometry analyses that go far beyond stoichiometric
      staining of DNA.

PMID- 30110134
TI  - Loss of neural crest-associated gene FOXD1 impairs melanoma invasion and
      migration via RAC1B downregulation.
AB  - Recent studies suggest that malignant melanoma heterogeneity includes
      subpopulations of cells with features of multipotent neural crest (NC) cells.
      Zebrafish and mouse models have shown that reactivation of neural crest-specific
      pathways during transformation determines the invasiveness of melanoma cells. In
      our study, we show that the neural crest-associated transcription factor FOXD1
      plays a key role in the invasion and the migration capacities of metastatic
      melanomas both in vivo and in vitro. Gene expression profiling analysis
      identified both an upregulation of FOXD1 in NC and melanoma cells, as well as a
      downregulation of several genes related to cell invasion in FOXD1 knockdown
      cells, including MMP9 and RAC1B. Furthermore, we demonstrate that knockdown of
      RAC1B a tumor-specific isoform of RAC1, significantly impaired melanoma cell
      migration and invasion and could abrogate enhanced invasiveness induced by FOXD1
      overexpression. We conclude that FOXD1 may influence invasion and migration via
      indirect regulation of MMP9 and RAC1B alternative splicing in melanoma cells.

PMID- 30110136
TI  - Long-term clinical outcome of single implants inserted flaplessly or
      conventionally.
AB  - BACKGROUND: Flapless implant surgery is mostly performed using guided surgical
      protocols, however, long-term studies on free-handed flapless surgery for single
      implants are lacking. PURPOSE: This prospective study evaluates bone level
      changes, peri-implant health, and complications of solitary implants placed using
      a conventional flap (F) or flaplessly (FL) after 6-9 years. MATERIALS AND
      METHODS: Fifty-three single TiUnite Branemark implants were originally inserted
      in 49 patients using an one-stage delayed loading protocol with flap (n = 27, F)
      or flaplessly (n = 26, FL) based on available bone volume and surgeon's decision
      making. Thirty-six patients with 37 implants participated in the prospective
      follow-up investigation 6-9 years later whereby survival, bone level changes,
      peri-implant health, and complications were assessed. RESULTS: After 88 months
      (range 76-107), all implants were survived. For F and FL combined, the overall
      average radiographic bone level was above the first implant thread, 1.26 mm
      apical of the implant-abutment junction (SD 1.08; 0-4.9) and statistically
      comparable. Bone loss from time of loading was 0.49 mm (SD 1.1; -1.3 to 2.8) for
      F and -0.89 mm (SD 1.0; -2.8 to 0.7) for FL (P < .01), suggesting regrowth of
      bone in FL due to initial countersinking. One implant (2.7%) had a probing depth
      above 5 mm. CONCLUSION: Free-handed flapless implant surgery for single implants
      with neighboring teeth is a predictable long-term treatment provided when there
      is sufficient bone volume.

PMID- 30110137
TI  - Lead-Free Solar Cells based on Tin Halide Perovskite Films with High Coverage and
      Improved Aggregation.
AB  - Two simple methods to improve tin halide perovskite film structure are
      introduced, aimed at increasing the power conversion efficiency of lead free
      perovskite solar cells. First, a hot antisolvent treatment (HAT) was found to
      increase the film coverage and prevent electrical shunting in the photovoltaic
      device. Second, it was discovered that annealing under a low partial pressure of
      dimethyl sulfoxide vapor increased the average crystallite size. The
      topographical and electrical qualities of the perovskite films are substantively
      improved as a result of the combined treatments, facilitating the fabrication of
      tin-based perovskite solar cell devices with power conversion efficiencies of
      over 7 %.

PMID- 30110139
TI  - Effect of different maintenance time of torque application on detorque values of
      abutment screws in full-arch implant-supported fixed prostheses.
AB  - BACKGROUND: The effect of different maintenance time of torque application and
      screw loosening in full-arch implant-supported prosthesis remains uninvestigated.
      PURPOSE: To examine the effect of different maintenance time of torque
      application on detorque values of implant abutment screw in full-arch implant
      supported fixed complete denture. MATERIALS AND METHODS: Passively fitting
      framework supported by four implants stabilized on resin model torqued to 35 N-cm
      and maintained for different times; instant torque application (protocol A), 10
      seconds (protocol B), and 30 seconds (protocol C) were used. Detorque values were
      recorded during removal of the screws. Comparison between mean torque and
      detorque values were made using paired sample t-test. The mean removal torque
      values of each protocol were compared using three-way analysis of variance
      (ANOVA). RESULTS: The mean removal torque values were lower than the applied
      torque for all the protocols. The highest mean removal torque value was found in
      the immediate protocol (A) (24.44 +/- 1.7), followed by the 30 seconds protocol
      (C) (23.37 +/- 1.75), and then by the 10 seconds protocol (B) (23.35 +/- 1.6).
      All these differences were found to be statistically significant between torque
      and detorque values (P = .001). However, the differences among detorque values
      were not statistically significant (P > .05). CONCLUSION: The application of 35 N
      cm for different maintenance time of torque application on implant abutment screw
      did not appear to affect the detorque value in a multiple implant-supported fixed
      prosthesis. Maintaining the torque for prolonged time (10 seconds or 30 seconds)
      was not significantly associated with higher preload than instant torque
      application in full-arch implant-supported prosthesis.

PMID- 30110138
TI  - flowIO: Flow cytometry standard conformance testing, editing, and export tool.
AB  - The Flow Cytometry Standard (FCS) format is a widely accepted norm for storing
      Flow Cytometry (FCM) data. Its goal as a standard is to allow FCM data sharing
      and re-analysis. Over more than three decades of its existence FCS has evolved
      into a well-defined, flexible file format reflecting technical changes in the FCM
      field. Its flexibility as well as rising numbers of instrument vendors leads to
      suboptimal implementations of FCS in some cases. Such situations compromise the
      primary goal of the standard and hinder the ability to reproduce FCM analyses. It
      is further underlined by rapid rise of advanced FCM analyses, often carried out
      outside traditional software tools and heavily relying on standard data storage
      and presentation. We have developed flowIO, an R package which tests FCS file
      conformance with the standard as defined by International Society for Advancement
      of Cytometry (ISAC) normative. Along with the package we provide a web based
      application (also at http://bioinformin.cesnet.cz/flowIO/) allowing user friendly
      access to the conformance testing as well as FCS file editing and export for
      further analysis.

PMID- 30110135
TI  - Circulating plasma phospholipid fatty acids and risk of pancreatic cancer in a
      large European cohort.
AB  - There are both limited and conflicting data on the role of dietary fat and
      specific fatty acids in the development of pancreatic cancer. In this study, we
      investigated the association between plasma phospholipid fatty acids and
      pancreatic cancer risk in the European Prospective Investigation into Cancer and
      Nutrition (EPIC) cohort. The fatty acid composition was measured by gas
      chromatography in plasma samples collected at recruitment from375 incident
      pancreatic cancer cases and375 matched controls. Associations of specific fatty
      acids with pancreatic cancer risk were evaluated using multivariable conditional
      logistic regression models with adjustment for established pancreatic cancer risk
      factors. Statistically significant inverse associations were found between
      pancreatic cancer incidence and levels of heptadecanoic acid (ORT3-T1 [odds ratio
      for highest versus lowest tertile] =0.63; 95%CI[confidence interval] = 0.41-0.98;
      ptrend = 0.036), n-3 polyunsaturated alpha-linolenic acid (ORT3-T1 = 0.60; 95%CI
      = 0.39-0.92; ptrend = 0.02) and docosapentaenoic acid (ORT3-T1 = 0.52; 95%CI =
      0.32-0.85; ptrend = 0.008). Industrial trans-fatty acids were positively
      associated with pancreatic cancer risk among men (ORT3-T1 = 3.00; 95%CI = 1.13
      7.99; ptrend = 0.029), while conjugated linoleic acids were inversely related to
      pancreatic cancer among women only (ORT3-T1 = 0.37; 95%CI = 0.17-0.81; ptrend =
      0.008). Among current smokers, the long-chain n-6/n-3 polyunsaturated fatty acids
      ratio was positively associated with pancreatic cancer risk (ORT3-T1 = 3.40;
      95%CI = 1.39-8.34; ptrend = 0.007). Results were robust to a range of sensitivity
      analyses. Our findings suggest that higher circulating levels of saturated fatty
      acids with an odd number of carbon atoms and n-3 polyunsaturated fatty acids may
      be related to lower risk of pancreatic cancer. The influence of some fatty acids
      on the development of pancreatic cancer may be sex-specific and modulated by
      smoking.

PMID- 30110144
TI  - Inkless Writing and Self-Erasing Security Feature of (Z)-1,2-Diarylacrylonitrile
      Based Materials: A Confidential Data Communication.
AB  - Development of a novel organic luminescent material for inkless writing, and self
      erasing application is a remarkable solution to reduce paper waste, recycling
      cost in the printing industry. These innovative materials also offer to reduce
      global warming due to the lower consumption of paper made from plants. To this
      endeavor, herein we report the design, synthesis and simple material fabrication
      of a donor-acceptor type (Z)-1,2-diarylacrylonitrile (1) compound, which in solid
      state displayed highly contrast and reversible vapochromism under the visible
      light as well as UV light. We found a unique multiphase luminescence switching
      from green (lambdamax = 535 nm) to yellow (lambdamax = 566 nm) and to orange-red
      (lambda = 580, 640 nm) in solid state. This multiphase switching is induced
      through the gradual exclusion of entrapped DMSO molecules from the crystalline
      rod-like materials. Utilizing this purely organic material, we have demonstrated
      reversible inkless writing/printing on a cellulose strip by employing
      photothermal effect of sunlight in which sunlight acts as an "inkless pen". We
      were able to print complex designs utilizing this technique, which is invisible
      in ambient light and brighter in UV light. To our delight, the writing is self
      erasable on keeping at sunlight for the prolonged period, upon keeping at ambient
      temperature, or instantly on warming. This remarkably smart function of our
      material offers cost-effective and environmentally benign technique for security
      data communication and confidential data printing.

PMID- 30110145
TI  - Using Magnetic Ions to Probe and Induce Magnetism of Pyrophosphates, Bacteria,
      and Mammalian Cells.
AB  - Magnetic isolation using magnetic nanoparticles (MNPs) as trapping probes have
      been widely used in sample pretreatment to shorten analysis time. Nevertheless,
      to generate MNPs is time-consuming. Furthermore, the generated MNPs have to be
      further functionalized to gain the capability of recognizing their target
      species. Thus, an alternative approach that can impose magnetism to nonmagnetic
      species by simply using magnetic ions as the probes is developed in this study.
      That is, we employ magnetic ions (Fe3+, Co2+, and Ni2+) that can interact with
      nonmagnetic species containing oxygen-containing functional groups as the probes.
      Pyrophosphate (PPi), bacteria, and mammalian cells were selected as the model
      samples. Our results show that the as-prepared magnetic ion-PPi conjugates gain
      sufficient magnetism and can be readily aggregated by applying an external
      magnetic field. Moreover, the magnetic trapping is reversible. The PPi-containing
      conjugates can lose their magnetic property simply using
      ethylenediaminetetraacetic acid or aluminum ions as competing agents to remove or
      to replace, respectively, the conjugated magnetic ions. In addition, bacteria and
      mammalian cells that possess abundant oxygen-containing functional groups on
      their cell surfaces can be selectively probed by magnetic ions and gain
      sufficient magnetism for magnetic isolation from complex serum samples.

PMID- 30110143
TI  - Oxygen Activation Switch in the Copper Amine Oxidase of Escherichia coli.
AB  - Copper amine oxidases (CuAOs) are metalloenzymes that reduce molecular oxygen to
      hydrogen peroxide during catalytic turnover of primary amines. In addition to
      Cu2+ in the active site, two peripheral calcium sites, ~32 A from the active
      site, have roles in Escherichia coli amine oxidase (ECAO). The buried Ca2+
      (Asp533, Leu534, Asp535, Asp678, and Ala679) is essential for full-length protein
      production, while the surface Ca2+ (Glu573, Tyr667, Asp670, and Glu672) modulates
      biogenesis of the 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor. The E573Q
      mutation at the surface site prevents calcium binding and TPQ biogenesis.
      However, TPQ biogenesis can be restored by a suppressor mutation (I342F) in the
      proposed oxygen delivery channel to the active site. While supporting TPQ
      biogenesis (~60% WTECAO TPQ), I342F/E573Q has almost no amine oxidase activity
      (~4.6% WTECAO activity). To understand how these long-range mutations have major
      effects on TPQ biogenesis and catalysis, we employed ultraviolet-visible
      spectroscopy, steady-state kinetics, inhibition assays, and X-ray
      crystallography. We show that the surface metal site controls the equilibrium
      (disproportionation) of the Cu2+-substrate reduced TPQ (TPQAMQ) Cu+-TPQ
      semiquinone (TPQSQ) couple. Removal of the calcium ion from this site by
      chelation or mutagenesis shifts the equilibrium to Cu2+-TPQAMQ or destabilizes
      Cu+-TPQSQ. Crystal structure analysis shows that TPQ biogenesis is stalled at
      deprotonation in the Cu2+-tyrosinate state. Our findings support WTECAO using the
      inner sphere electron transfer mechanism for oxygen reduction during catalysis,
      and while a Cu+-tyrosyl radical intermediate is not essential for TPQ biogenesis,
      it is required for efficient biogenesis.

PMID- 30110146
TI  - Versatile Bioconjugation Chemistries of ortho-Boronyl Aryl Ketones and Aldehydes.
AB  - Biocompatible and bioorthogonal conjugation reactions have proven to be powerful
      tools in biological research and medicine. While the advent of bioorthogonal
      conjugation chemistries greatly expands our capacity to interrogate specific
      biomolecules in situ, biocompatible reactions that target endogenous reactive
      groups have given rise to a number of covalent drugs as well as a battery of
      powerful research tools. Despite the impressive progress, limitations do exist
      with the current conjugation chemistries. For example, most known bioorthogonal
      conjugations suffer from slow reaction rates and imperfect bioorthogonality. On
      the other hand, covalent drugs often display high toxicity due to off-target
      labeling and immunogenicity. These limitations demand continued pursuit of
      conjugation chemistries with optimal characteristics for biological applications.
      A spate of papers appearing in recent literature report the conjugation
      chemistries of 2-formyl and 2-acetyl phenylboronic acids (abbreviated as 2-FPBA
      and 2-APBA, respectively). These simple reactants are found to undergo fast
      conjugation with various nucleophiles under physiological conditions, showing
      great promise for biological applications. The versatile reactivity of 2-FPBA and
      2-APBA manifests in dynamic conjugation with endogenous nucleophiles as well as
      conjugation with designer nucleophiles in a bioorthogonal manner. 2-FPBA/APBA
      conjugates with amines in biomolecules, such as lysine side chains and
      aminophospholipids, in a highly dynamic manner to give iminoboronates. In
      contrast to typical imines, iminoboronates enjoy much improved thermodynamic
      stability, yet are kinetically labile for hydrolysis due to imine activation by
      the boronic acid. Dynamic conjugations as such present a novel binding mechanism
      analogous to hydrogen bonding and electrostatic interactions. Implementation of
      this covalent binding mechanism has yielded reversible covalent probes of
      prevalent bacterial pathogens. It has also resulted in reversible covalent
      inhibitors of a therapeutically important protein Mcl-1. Such covalent
      probes/inhibitors with 2-FPBA/APBA warheads avoid permanent modification of their
      biological target, potentially able to mitigate off-target labeling and
      immunogenicity of covalent drugs. The dynamic conjugation of 2-FPBA/APBA has been
      recently extended to N-terminal cysteines, which can be selectively targeted via
      formation of a thiazolidino boronate (TzB) complex. The dynamic TzB formation
      expands the toolbox for site-specific protein labeling and the development of
      covalent drugs. On the front of bioorthogonal conjugation, 2-FPBA/APBA has been
      found to conjugate with alpha-nucleophiles under physiologic conditions with rate
      constant ( k2) over 1000 M-1 s-1, which overcomes the slow kinetics problems and
      rekindles the interest of using the conjugation of alpha-nucleophiles for
      biological studies. With fast kinetics being a shared feature, this family of
      conjugation chemistries gives remarkably diverse product structures depending on
      the choice of nucleophile. Importantly, both dynamic and irreversible
      conjugations have been developed, which we believe will enable a wide array of
      applications in biological research. In this Account, we collectively examine
      this rapidly expanding family of conjugation reactions, seeking to elucidate the
      unifying principles that would guide further development of novel conjugation
      reactions, as well as their applications in biology.

PMID- 30110147
TI  - Controlling Electrons and Protons through Theory: Molecular Electrocatalysts to
      Nanoparticles.
AB  - The development of renewable energy sources that are environmentally friendly and
      economical is of critical importance. The effective utilization of such energy
      sources relies on catalysts to facilitate the interconversion between electrical
      and chemical energy through multielectron, multiproton reactions. The design of
      effective catalysts for these types of energy conversion processes requires the
      ability to control the localization and movement of electrons and protons, as
      well as the coupling between them. Theoretical calculations, in conjunction with
      experimental validation and feedback, are playing a key role in these catalyst
      design efforts. A general theory has been developed for describing proton-coupled
      electron transfer (PCET) reactions, which encompass all reactions involving the
      coupled transfer of electrons and protons, including sequential and concerted
      mechanisms for multielectron, multiproton processes. In addition, computational
      methods have been devised to compute the input quantities for the PCET rate
      constant expressions and to generate free energy pathways for molecular
      electrocatalysts. These methods have been extended to heterogeneous PCET
      reactions to enable the modeling of PCET processes at electrode and nanoparticle
      surfaces. Three distinct theoretical studies of PCET reactions relevant to
      catalyst design for energy conversion processes are discussed. In the first
      application, theoretical calculations of hydrogen production catalyzed by hangman
      metalloporphyrins predicted that the porphyrin ligand is reduced, leading to
      dearomatization and proton transfer from the carboxylic acid hanging group to the
      meso carbon of the porphyrin rather than the metal center, producing a phlorin
      intermediate. Subsequent experiments isolated and characterized the phlorin
      intermediate, validating this theoretical prediction. These molecular
      electrocatalysts exemplify the potential use of noninnocent ligands to localize
      electrons and protons on different parts of the catalyst and to direct their
      motions accordingly. In the second application, theoretical calculations on
      substituted benzimidazole phenol molecules predicted that certain substituents
      would lead to multiple intramolecular proton transfer reactions upon oxidation.
      Subsequent experiments verified these multiproton reactions, as well as the
      predicted shifts in the redox potentials and kinetic isotope effects. These
      bioinspired molecular systems demonstrate the potential use of multiproton relays
      to enable the transport of protons over longer distances along specified
      pathways, as well as the tuning of redox potentials through this movement of
      positive charge. In the third application, theoretical studies of heterogeneous
      PCET in photoreduced ZnO nanoparticles illustrated the significance of proton
      diffusion through the bulk of the nanoparticle as well as interfacial PCET to an
      organic radical in solution at its surface. These theoretical calculations were
      consistent with prior experimental studies of this system, although theoretical
      methods for heterogeneous PCET have not yet attained the level of predictive
      capability highlighted for the molecular electrocatalysts. These examples suggest
      that theory will play a significant role in the design of both molecular and
      heterogeneous catalysts to control the movement and coupling of electrons and
      protons. The resulting catalysts will be essential for the development of
      renewable energy sources to address current energy challenges.

PMID- 30110148
TI  - Lactobionic/Folate Dual-Targeted Amphiphilic Maltodextrin-Based Micelles for
      Targeted Codelivery of Sulfasalazine and Resveratrol to Hepatocellular Carcinoma.
AB  - In this study, promising approaches of dual-targeted micelles and drug-polymer
      conjugation were combined to enable injection of poorly soluble anticancer drugs
      together with site-specific drug release. Ursodeoxycholic acid (UDCA) as a
      hepatoprotective agent was grafted to maltodextrin (MD) via carbodiimide coupling
      to develop amphiphilic maltodextrin-ursodeoxycholic acid (MDCA)-based micelles.
      Sulfasalazine (SSZ), as a novel anticancer agent, was conjugated via a tumor
      cleavable ester bond to MD backbone to obtain tumor-specific release, whereas
      resveratrol (RSV) was physically entrapped within the hydrophobic micellar core.
      For maximal tumor-targeting, both folic acid (FA) and lactobionic acid (LA) were
      coupled to the surface of micelles to obtain dual-targeted micelles. The decrease
      of critical micelle concentration (CMC) from 0.012 to 0.006 mg/mL declares the
      significance of a dual hydrophobicized core of micelles by both UDCA and SSZ. The
      dual-targeted micelles showed a great hemocompatibility, as well as enhanced
      cytotoxicity and internalization into HepG-2 liver cancer cells via binding to
      overexpressed folate and asialoglycoprotein receptors. In vivo, the micelles
      demonstrated superior antitumor effects revealed as reduction in the liver/body
      weight ratio, inhibition of angiogenesis, and enhanced apoptosis. Overall,
      combined strategies of dual active targeted micelles with bioresponsive drug
      conjugation could be utilized as a promising approach for tumor-targeted drug
      delivery.

PMID- 30110149
TI  - Functional Nanoparticles-Coated Nanomechanical Sensor Arrays for Machine Learning
      Based Quantitative Odor Analysis.
AB  - A sensing signal obtained by measuring an odor usually contains varied
      information that reflects an origin of the odor itself, while an effective
      approach is required to reasonably analyze informative data to derive the desired
      information. Herein, we demonstrate that quantitative odor analysis was achieved
      through systematic material design-based nanomechanical sensing combined with
      machine learning. A ternary mixture consisting of water, ethanol, and methanol
      was selected as a model system where a target molecule coexists with structurally
      similar species in a humidified condition. To predict the concentration of each
      species in the system via the data-driven approach, six types of nanoparticles
      functionalized with hydroxyl, aminopropyl, phenyl, and/or octadecyl groups were
      synthesized as a receptor coating of a nanomechanical sensor. Then, a machine
      learning model based on Gaussian process regression was trained with sensing data
      sets obtained from the samples with diverse concentrations. As a result, the
      octadecyl-modified nanoparticles enhanced prediction accuracy for water while the
      use of both octadecyl and aminopropyl groups was indicated to be a key for a
      better prediction accuracy for ethanol and methanol. As the prediction accuracy
      for ethanol and methanol was improved by introducing two additional nanoparticles
      with finely controlled octadecyl and aminopropyl amount, the feedback obtained by
      the present machine learning was effectively utilized to optimize material design
      for better performance. We demonstrate through this study that various
      information which was extracted from plenty of experimental data sets was
      successfully combined with our knowledge to produce wisdom for addressing a
      critical issue in gas phase sensing.

PMID- 30110150
TI  - Lanthanide Functionalized Metal-Organic Coordination Polymer: Toward Novel Turn
      On Fluorescent Sensing of Amyloid beta-Peptide.
AB  - Metal-organic coordination polymers (MOCPs) have been emerging as very attractive
      nanomaterials due to their tunable nature and diverse applications. Herein, using
      Tb3+ as the luminescence center, 1,3,5-benzenetricarboxylate (BTC) as building
      block and Cu2+ as the signal modulator as well as a recognition unit, we propose
      a novel and effective lanthanide functionalized MOCP (LMOCP) fluorescent sensor
      (Cu-BTC/Tb) for amyloid beta-peptide (Abeta) monomer, a biomarker for Alzheimer
      disease (AD). Specifically, Cu-BTC/Tb, created by postsynthesis modification
      strategy under room temperature, is almost nonemissive due to the quenching
      effect of Cu2+ in the MOCP, exhilaratingly, the presence of Abeta1-40 triggered a
      significant emission enhancement of Cu-BTC/Tb assay due to the high binding
      affinity of Abeta1-40 for Cu2+ and the subsequent suppression of the quenching
      effect. In the assay, this LMOCP sensor shows high sensitivity with detection
      limit of 0.3 nM. Due to its capability to eliminate autofluorescence, Cu-BTC/Tb
      was also applied to the time-gated detection of Abeta1-40 in human plasma with
      promising results. This work presents a novel strategy for the construction of
      functional luminescent LMOCP for sensitively turn-on fluorescent sensing of
      Abeta1-40. We believe the proposed strategy would inspire the development of
      various LMOCP-based fluorescent assays or medical imaging platforms for advanced
      biological implementations.

PMID- 30110151
TI  - Structural Properties of Al-O Monolayers in SiO2 on Silicon and the Maximization
      of Their Negative Fixed Charge Density.
AB  - Al2O3 on Si is known to form an ultrathin interfacial SiO2 during deposition and
      subsequent annealing, which creates a negative fixed charge ( Qfix) that enables
      field-effect passivation and low surface recombination velocities in Si solar
      cells. Various concepts were suggested to explain the origin of this negative
      Qfix. In this study, we investigate Al-O monolayers (MLs) from atomic layer
      deposition (ALD) sandwiched between deliberately grown/deposited SiO2 films. We
      show that the Al atoms have an ultralow diffusion coefficient (~4 * 10-18 cm2/s
      at 1000  degrees C), are deposited at a constant rate of ~5 * 1014 Al atoms/(cm2
      cycle) from the first ALD cycle, and are tetrahedral O-coordinated because the
      adjacent SiO2 imprints its tetrahedral near-order and bond length into the Al-O
      MLs. By variation in the tunnel-SiO2 thickness and the number of Al-O MLs, we
      demonstrate that the tetrahedral coordination alone is not sufficient for the
      formation of Qfix but that a SiO2/Al2O3 interface within a tunneling distance
      from the substrate must be present. The Al-induced acceptor states at these
      interfaces have energy levels slightly below the Si valence band edge and require
      charging by electrons from either the Si substrate or from Si/SiO2 dangling bonds
      to create a negative Qfix. Hence, tunneling imposes limitations for the SiO2 and
      Al2O3 layer thicknesses. In addition, Coulomb repulsion between the charged
      acceptor states results in an optimum number of Al-O MLs, i.e., separation of
      both interfaces. We achieve maximum negative Qfix of ~5 * 1012 cm-2 (comparable
      to thick ALD-Al2O3 on Si) with ~1.7 nm tunnel-SiO2 and just seven ALD-Al2O3
      cycles (~8 A) after optimized annealing at 850  degrees C for 30 s. The findings
      are discussed in the context of a passivating, hole-selective tunnel contact for
      high-efficiency Si solar cells.

PMID- 30110152
TI  - Human Skin-Like, Robust Waterproof, and Highly Breathable Fibrous Membranes with
      Short Perfluorobutyl Chains for Eco-Friendly Protective Textiles.
AB  - Flexible smart membranes with superior waterproofness and extreme breathability
      are highly desirable for wearable uses. However, present waterproof and
      breathable materials suffer from limited performance efficiency, alarming
      environmental risks, and complicated fabrication procedures. We report on eco
      friendly fibrous membranes with human skin-like, robust waterproof, and highly
      breathable capabilities that can be prepared via a facile electrospinning
      strategy. A novel polyurethane elastomer (C4FPU) possessing double-terminal short
      perfluorobutyl (-C4F9) chain is synthesized for the first time and incorporated
      into the polyurethane (PU) fiber matrix, endowing the membrane with mighty and
      durable hydrophobicity. Additionally, the employment of AgNO3 greatly decreased
      the maximum pore size ( dmax), contributing to the dramatically enhanced
      waterproofness. The resulting PU/C4FPU/AgNO3 fibrous membranes exhibit
      comprehensive properties of exceptional hydrostatic pressure (102.8 kPa),
      excellent water vapor transmission rate (12.9 kg m-2 d-1), high mechanical
      property (9.8 MPa), and significant antibacterial efficacy against Escherichia
      coli and Staphylococcus aureus. The successful synthesis of these intriguing
      membranes may provide a promising candidate for the new generation of key
      building blocks of the upscale protective garments.

PMID- 30110153
TI  - SERS-Based Quantification of Biomarker Expression at the Single Cell Level
      Enabled by Gold Nanostars and Truncated Aptamers.
AB  - Surface-enhanced Raman spectroscopy (SERS)-based biosensors have been used
      increasingly over the past few years for cancer detection and diagnosis. SERS
      based imaging offers excellent sensitivity and has advantages over other
      detection techniques such as fluorescence. In this study, we developed a novel
      biosensor to detect the cancer biomarker epithelial cell adhesion molecule
      (EpCAM) and quantify its expression at the single cell level. EpCAM is one of the
      most commonly expressed markers on a variety of cancer cells; importantly it has
      been suggested that reduction of its expression levels could be associated with
      the epithelial to mesenchymal transition (EMT) and thus to the onset of
      metastasis. Therefore, monitoring variations in expression levels of this
      membrane biomarker would improve our ability to monitor cancer progression. The
      described substrate-based biosensor was developed employing gold nanostars
      functionalized with EpCAM aptamer molecules and was able to quantify subnanomolar
      concentrations of EpCAM protein in solution. Importantly, we demonstrated its use
      to quantify EpCAM expression on the surface of two cancer cells, MCF-7 and PC-3.
      We also compared the binding efficiency of two EpCAM DNA aptamers of different
      lengths and observed a substantial improvement in the sensitivity of detection by
      employing the shorter aptamer sequence, probably due to the reduced number of
      conformations possible at room temperature with the truncated oligonucleotide.
      Detailed characterization of the substrates was carried out using both SERS maps
      and atomic force microscopy. These substrate-based diagnostic devices promise to
      be relevant for monitoring phenotype evolutions in cancer cells, blood, and other
      bodily fluids, thus improving our ability to follow in real time disease onset
      and progression.

PMID- 30110154
TI  - A YopH PTP1B Chimera Shows the Importance of the WPD-Loop Sequence to the
      Activity, Structure, and Dynamics of Protein Tyrosine Phosphatases.
AB  - To study factors that affect WPD-loop motion in protein tyrosine phosphatases
      (PTPs), a chimera of PTP1B and YopH was created by transposing the WPD loop from
      PTP1B to YopH. Several subsequent mutations proved to be necessary to obtain a
      soluble, active enzyme. That chimera, termed chimera 3, retains productive WPD
      loop motions and general acid catalysis with a pH dependency similar to that of
      the native enzymes. Kinetic isotope effects show the mechanism and transition
      state for phosphoryl transfer are unaltered. Catalysis of the chimera is slower
      than that of either of its parent enzymes, although its rate is comparable to
      those of most native PTPs. X-ray crystallography and nuclear magnetic resonance
      were used to probe the structure and dynamics of chimera 3. The chimera's
      structure was found to sample an unproductive hyper-open conformation of its WPD
      loop, a geometry that has not been observed in either of the parents or in other
      native PTPs. The reduced catalytic rate is attributed to the protein's sampling
      of this conformation in solution, reducing the fraction in the catalytically
      productive loop-closed conformation.

PMID- 30110156
TI  - Hierarchically Ordered Two-Dimensional Coordination Polymers Assembled from Redox
      Active Dimolybdenum Clusters.
AB  - Coordination polymers (CPs) supporting tunable through-framework conduction and
      responsive properties are of significant interest for enabling a new generation
      of active devices. However, such architectures are rare. We report a redox-active
      CP composed of two-dimensional (2D) lattices of coordinatively bonded Mo2(INA)4
      clusters (INA = isonicotinate). The 2D lattices are commensurately stacked and
      their ordering topology can be synthetically tuned. The material has a
      hierarchical pore structure (pore sizes distributed between 7 and 33 A) and
      exhibits unique CO2 adsorption (nominally Type VI) for an isotherm collected at
      195 K. Furthermore, cyclic voltammetry and electrokinetic analyses identify a
      quasi-reversible feature at E1/2 = -1.275 V versus ferrocene/ferrocenium that can
      be ascribed to the [Mo2(INA)4]0/-1 redox couple, with an associated standard
      heterogeneous electron transfer rate constant ks = 1.49 s-1. The tunable
      structure, porosity, and redox activity of our material may render it a promising
      platform for CPs with responsive properties.

PMID- 30110155
TI  - O2-Tolerant H2 Activation by an Isolated Large Subunit of a [NiFe] Hydrogenase.
AB  - The catalytic properties of hydrogenases are nature's answer to the seemingly
      simple reaction H2 ? 2H+ + 2e-. Members of the phylogenetically diverse subgroup
      of [NiFe] hydrogenases generally consist of at least two subunits, where the
      large subunit harbors the H2-activating [NiFe] site and the small subunit
      contains iron-sulfur clusters mediating e- transfer. Typically, [NiFe]
      hydrogenases are susceptible to inhibition by O2. Here, we conducted system
      minimization by isolating and analyzing the large subunit of one of the rare
      members of the group of O2-tolerant [NiFe] hydrogenases, namely the preHoxG
      protein of the membrane-bound hydrogenase from Ralstonia eutropha. Unlike
      previous assumptions, preHoxG was able to activate H2 as it clearly performed
      catalytic hydrogen/deuterium exchange. However, it did not execute the entire
      catalytic cycle described for [NiFe] hydrogenases. Remarkably, H2 activation was
      performed by preHoxG even in the presence of O2, although the unique [4Fe-3S]
      cluster located in the small subunit and described to be crucial for tolerance
      toward O2 was absent. These findings challenge the current understanding of O2
      tolerance of [NiFe] hydrogenases. The applicability of this minimal hydrogenase
      in basic and applied research is discussed.

PMID- 30110157
TI  - Accurate Spin-State Energetics for Aryl Carbenes.
AB  - A test set of 12 aryl carbenes (AC12) is compiled with the purpose of
      establishing their adiabatic singlet-triplet energy splittings using correlated
      wave function based methods. The set covers both singlet and triplet ground state
      aryl carbenes, as well as a range of magnitudes for the ground state to excited
      state gap. The performance of coupled cluster methods is examined with respect to
      the reference wave function, the basis set, and a number of additional
      methodological parameters that enter the calculation. Inclusion of perturbative
      triples and basis set extrapolation with a combination of triple and quadruple
      zeta basis sets are both required to ensure high accuracy. When canonical coupled
      cluster calculations become too expensive, the domain-based local pair natural
      orbital approach DLPNO-CCSD(T) can be used as a reliable method for larger
      systems, as it achieves a mean absolute error of only 0.2 kcal/mol for the
      singlet-triplet gaps in the present test set. Other first-principles wave
      function methods and selected density functional methods are also evaluated.
      Second-order Moller-Plesset perturbation theory approaches are only applicable in
      conjunction with orbital optimization (OO-MP2). Among the representative density
      functional methods tested, only double hybrid functionals perform sufficiently
      accurately to be considered useful for systems with small singlet-triplet gaps.
      On the basis of the reference coupled cluster results, projected gas-phase free
      energies are reported for all aryl carbenes. Finally, the treatment of singlet
      triplet gaps in solution is discussed in terms of both implicit and explicit
      solvation.

PMID- 30110158
TI  - Tunability of Biodegradable Poly(amine- co-ester) Polymers for Customized Nucleic
      Acid Delivery and Other Biomedical Applications.
AB  - Gene therapy promises to treat diseases that arise from genetic abnormalities by
      correcting the underlying cause of the disease rather than treating the
      associated symptoms. Successful transfer of nucleic acids into cells requires
      efficient delivery vehicles that protect the cargo and can penetrate the
      appropriate cellular barriers before releasing their contents. Many viral vectors
      and synthetic polycationic vectors for nucleic acid delivery do not translate
      well from in vitro to in vivo applications due to their instability and toxicity.
      We synthesized and characterized a library of biocompatible low charge density
      polymers from a family of poly(amine- co-ester) (PACE) terpolymers produced via
      enzyme catalyzed polymerization. PACE polymers are highly customizable; we found
      that the terpolymer composition can be optimized to produce efficient
      transfection of various nucleic acids-including DNA plasmids, mRNA, and siRNA-in
      specific cell types with low toxicity. Our findings suggest that the unique
      tunability of PACEs offers new tools for gene therapy and other biomedical
      applications.

PMID- 30110159
TI  - Indoxyl Sulfate Generates Free Radicals, Decreases Antioxidant Defense, and Leads
      to Damage to Mononuclear Blood Cells.
AB  - Indoxyl sulfate (IS) is a uremic toxin that has been associated with inflammation
      and oxidative stress as well as with the progression of chronic kidney disease
      (CKD). IS is a protein metabolite that is concentrated in the serum of CKD
      patients. IS is a well-known uremic toxin, but there are very few reports on the
      effect of IS on cells including mononuclear cells (MNCs). We hypothesized that a
      high concentration of IS in CKD patients may induce changes in redox balance in
      the in vitro cells exposed. In the present study, we investigated the effect of
      IS on free radical production, antioxidant capacity, and protein damage in the
      mononuclear blood cells. As already determined, the concentrations (0.2 or 1 mM)
      of IS used in this study do not affect the survival rate of MNCs. For both the
      concentrations of IS, there was an increase in superoxide and nitric oxide and a
      release of other reactive oxygen species (ROS) inside the cells, as measured
      using fluorescent probes. However, an increase in other ROS as indicated by H2DCF
      DA was found only for 1 mM of IS. Moreover, a decrease in the non-enzymatic
      antioxidant capacity and an increase in the superoxide dismutase activity after
      incubation of the cells with IS were observed. Furthermore, we found an increase
      in the levels of carbonyl compounds and peroxides in the cells treated with both
      the concentrations of IS. The obtained results show that IS induces oxidative
      stress and a decrease in antioxidant defense in cells leading to lipid and
      protein damage.

PMID- 30110160
TI  - Correction to Nanofertilizers: New Products for the Industry?

PMID- 30110161
TI  - Removal of A-Site Alkali and Alkaline Earth Metal Cations in KBe2BO3F2-Type
      Layered Structures To Enhance the Deep-Ultraviolet Nonlinear Optical Capability.
AB  - In order to generate deep-ultraviolet (DUV, lambda < 200 nm) coherent light, many
      DUV-transparent nonlinear optical (NLO) compounds have been synthesized
      experimentally over the past few decades, most of which contain alkali or/and
      alkaline earth metal cations. However, to date, practical DUV NLO materials
      beyond KBe2BO3F2 (KBBF) are still very scarce. In this work, based on analysis of
      the DUV NLO effect induced by the A-site alkali and alkaline earth metal cations,
      we attempt to expand the options for DUV NLO compounds from a molecular
      engineering point of view. Accordingly, a useful strategy is proposed to design
      densely stacked layered structures without A-site cations as new and promising
      DUV NLO materials. Along with the available experimental and first-principles
      calculation results, it is demonstrated that layered structures in which the A
      site cations are removed, such as Be2BO3F, Be2CO3F2, AlCO3F, SiCO3F2, AlNO3F2,
      PBO3F2, and PB3O6F2, whether real or hypothetical, exhibit excellent DUV NLO
      performances. Based on the findings, our strategy may open up new opportunities
      for the design and exploration of high-performance DUV NLO materials beyond KBBF.

PMID- 30110162
TI  - Resurrection Biology: Aged Acetylcholinesterase Brought Back to Life.
AB  - Organophosphorus agents such as sarin and soman that phosphylate the active site
      serine of the enzyme acetylcholinesterase are notorious and pernicious, not only
      because they have been used by tyrants to effect mass murder of their own
      populations but also because they are sought by terrorists to inflict mass
      casualties on civilian populations. These threats underscore the need to develop
      effective antidotes against such agents. Phosphylation of acetylcholinesterase
      produces two adducts, an initial neutral adduct that can be reactivated with
      oxime nucleophiles, and a subsequent monoanionic adduct (called aged
      acetylcholinesterase) which has proven over two generations to be impervious to
      reactivation. This Viewpoint discusses a recent article in the journal that
      describes the first successful efforts to resurrect the activity of aged
      acetylcholinesterase.

PMID- 30110164
TI  - Positron Emission Tomography (PET) Ligand Development for Ionotropic Glutamate
      Receptors: Challenges and Opportunities for Radiotracer Targeting N-Methyl-d
      aspartate (NMDA), alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
      (AMPA), and Kainate Receptors.
AB  - Ionotropic glutamate receptors (iGluRs) mediate excitatory neurotransmission
      within the mammalian central nervous system. iGluRs exist as three main groups: N
      methyl-d-aspartate receptors (NMDARs), alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid receptors (AMPARs), and kainate receptors. The past
      decades have witnessed a remarkable development of PET tracers targeting
      different iGluRs including NMDARs and AMPARs, and several of the tracers have
      advanced to clinical imaging studies. Here, we assess the recent development of
      iGluR PET probes, focusing on tracer design, brain kinetics, and performance in
      PET imaging studies. Furthermore, this review will not only present challenges in
      the tracer development but also provide novel approaches in conjunction with most
      recent drug discovery efforts on these iGluRs, including subtype-selective NMDAR
      and transmembrane AMPAR regulatory protein modulators and positive allosteric
      modulators (PAMs) of AMPARs. These approaches, if successful as PET tracers, may
      provide fundamental knowledge to understand the roles of iGluR receptors under
      physiological and pathological conditions.

PMID- 30110163
TI  - Crystal Structure of NaLuW2O8.2H2O and Down/Upconversion Luminescence of the
      Derived NaLu(WO4)2:Yb/Ln Phosphors (Ln = Ho, Er, Tm).
AB  - Hydrothermally reacting Lu(NO)3 and Na2WO4.2H2O at 200  degrees C and pH = 8
      produced the new compound NaLuW2O8.2H2O, which was analyzed via the Rietveld
      technique to crystallize in the orthorhombic system (space group: Cmmm) with cell
      parameters a = 21.655(1), b = 5.1352(3), and c = 3.6320(2) A and cell volume V =
      403.87(4) A3. The crystal structure presents -(NaO6)-(NaO6)- and -(LuO4(H2O)2WO5)
      (LuO4(H2O)2WO5)- alternating layers linked together by the O2- ion common to NaO6
      octahedron and WO5 triangle bipyramid. Tetragonal structured and phase-pure
      Na(Lu0.87Ln0.03Yb0.1)(WO4)2 phosphors (Ln = Ho, Er, and Tm) were directly
      produced by calcining their NaLuW2O8.2H2O analogous precursors at 600  degrees C
      for 2 h, followed by a detailed study of their downconversion/upconversion
      (DC/UC) photoluminescence. It was shown that the UC luminescence is dominated by
      a red band at ~650 nm for Ho3+ (5F5 -> 5I8 transition), green bands at ~500-575
      nm for Er3+ (2H11/2/4S3/2 -> 4I15/2 transitions) and a blue band at ~476 nm for
      Tm3+ (1G4 -> 3H6 transition), all via a three-photon process. DC luminescence of
      the phosphors is characterized by a ~545 nm green emission for Ho3+ (5F4/5S2 ->
      5I8 transition, lambdaex = 453 nm), ~500-575 nm green emissions for Er3+
      (2H11/2/4S3/2 -> 4I15/2 transitions, lambdaex = 380 nm), and a ~455 nm blue
      emission for Tm3+ (1D2 -> 3F4 transition, lambdaex = 360 nm), with CIE
      chromaticity coordinates of around (0.27, 0.71), (0.26, 0.72), and (0.15, 0.04),
      respectively.

PMID- 30110165
TI  - Chromium(III)-Catalyzed Addition of Water and Alcohol to alpha,beta-Unsaturated
      Ketones for the Synthesis of beta-Hydroxyl and beta-Alkoxyl Ketones in Aqueous
      Media.
AB  - An efficient chromium(III) chloride-catalyzed Michael-type reaction of water or
      alcohol with alpha,beta-unsaturated ketones is developed. A variety of alpha,beta
      unsaturated ketones effectively reacted with either water or alcohols to give the
      corresponding beta-hydroxyl ketones or beta-alkoxyl ketones in modest to high
      yields with excellent compatibility to various functional groups. The approach
      was further utilized for the preparation of synthetically useful compounds
      containing tetrahydrofuran skeleton.

PMID- 30110166
TI  - Benzylic Thio and Seleno Newman-Kwart Rearrangements.
AB  - The thermally induced OBn -> SBn and OBn -> SeBn migration reactions facilitate
      the rearrangement of O-benzyl thio- and selenocarbamates [BnOC(?X)NMe2] (X = S or
      Se) into their corresponding S-benzyl thio- and Se-benzyl selenocarbamates
      [BnXC(?O)NMe2] (X = S or Se). A series of substituted O-benzyl thio- and
      selenocarbamates were synthesized and rearranged in good yields of 33-88%. The
      reaction rates are higher for substrates with electron-donating groups in the 2
      or 4 position of the aromatic ring, but the rearrangement also proceeds with
      electron-withdrawing substituents. The rearrangement follows first-order reaction
      kinetics and proceeds via a tight ion pair intermediate consisting of the
      benzylic carbocation and the thio- or selenocarbamate moiety. Computational
      studies support these findings.

PMID- 30110168
TI  - Multienzyme One-Pot Cascade for the Stereoselective Hydroxyethyl
      Functionalization of Substituted Phenols.
AB  - The operability and substrate scope of a redesigned vinylphenol hydratase as a
      single biocatalyst or as part of multienzyme cascades using either substituted
      coumaric acids or phenols as stable, cheap, and readily available substrates are
      reported.

PMID- 30110169
TI  - Bronsted Base-Catalyzed Reductive Cyclization of Alkynyl alpha-Iminoesters
      through Auto-Tandem Catalysis.
AB  - A novel reductive cyclization of alkynyl alpha-iminoesters was developed through
      auto-tandem catalysis with a Bronsted base as the catalyst. The reaction system
      involves two mechanistically different elementary processes, both of which are
      efficiently catalyzed by an organosuperbase P2- tBu: the unprecedented reduction
      of alpha-iminoesters with 1-dodecanethiol as the reductant to provide alpha
      aminoesters and the following intramolecular addition of ester enolates to an
      alkyne. The operationally simple reaction under mild conditions provides new
      efficient access to N-H indoline derivatives, demonstrating the high potential of
      auto-tandem catalysis with a Bronsted base as a methodology for organic
      synthesis.

PMID- 30110167
TI  - Complete Genome of Micromonospora sp. Strain B006 Reveals Biosynthetic Potential
      of a Lake Michigan Actinomycete.
AB  - Actinomycete bacteria isolated from freshwater environments are an unexplored
      source of natural products. Here we report the complete genome of the Great Lakes
      derived Micromonospora sp. strain B006, revealing its potential for natural
      product biosynthesis. The 7-megabase pair chromosome of strain B006 was sequenced
      using Illumina and Oxford Nanopore technologies followed by Sanger sequencing to
      close remaining gaps. All identified biosynthetic gene clusters (BGCs) were
      manually curated. Five known BGCs were identified encoding desferrioxamine, alkyl
      O-dihydrogeranylmethoxyhydroquinone, a spore pigment, sioxanthin, and
      diazepinomicin, which is currently in phase II clinical trials to treat Phelan
      McDermid syndrome and co-morbid epilepsy. We report here that strain B006 is
      indeed a producer of diazepinomicin and at yields higher than previously
      reported. Moreover, 11 of the 16 identified BGCs are orphan, eight of which were
      transcriptionally active under the culture condition tested. Orphan BGCs include
      an enediyne polyketide synthase and an uncharacteristically large, 36-module
      polyketide synthase-nonribosomal peptide synthetase BGC. We developed a genetics
      system for Micromonospora sp. B006 that will contribute to deorphaning BGCs in
      the future. This study is one of the few attempts to report the biosynthetic
      capacity of a freshwater-derived actinomycete and highlights this resource as a
      potential reservoir for new natural products.

PMID- 30110171
TI  - Borinic Acid/Halide Co-catalyzed Semipinacol Rearrangements of 2,3-Epoxy
      Alcohols.
AB  - A new mode of catalysis of the semipinacol rearrangement of 2,3-epoxy alcohols is
      described. In combination with a halide salt additive, diarylborinic acids
      promote a Type II rearrangement that occurs with net retention of configuration.
      This unusual stereochemical outcome is consistent with a mechanism involving
      regioselective ring opening of the epoxy alcohol by halide, followed by
      rearrangement of the resulting halohydrin-derived borinic ester. The protocol is
      applicable to a range of substrates, enabling ring contractions and expansions as
      well as stereospecific syntheses of acyclic beta-hydroxycarbonyl compounds.

PMID- 30110170
TI  - N-Linked Glycan Branching and Fucosylation Are Increased Directly in Hcc Tissue
      As Determined through in Situ Glycan Imaging.
AB  - Hepatocellular carcinoma (HCC) remains as the fifth most common cancer in the
      world and accounts for more than 700,000 deaths annually. Changes in serum
      glycosylation have long been associated with this cancer but the source of that
      material is unknown and direct glycan analysis of HCC tissues has been limited.
      Our laboratory previously developed a method of in situ tissue based N-linked
      glycan imaging that bypasses the need for microdissection and solubilization of
      tissue prior to analysis. We used this methodology in the analysis of 138 HCC
      tissue samples and compared the N-linked glycans in cancer tissue with either
      adjacent untransformed or tissue from patients with liver cirrhosis but no
      cancer. Ten glycans were found significantly elevated in HCC tissues as compared
      to cirrhotic or adjacent tissue. These glycans fell into two major classes, those
      with increased levels of fucosylation and those with increased levels of
      branching with or without any fucose modifications. In addition, increased levels
      of fucosylated glycoforms were associated with a reduction in survival time. This
      work supports the hypothesis that the increased levels of fucosylated N-linked
      glycans in HCC serum are produced directly from the cancer tissue.

PMID- 30110172
TI  - Exploitation of Cyclopropane Carbaldehydes to Prins Cyclization: Quick Access to
      ( E)-Hexahydrooxonine and Octahydrocyclopenta[ b]pyran.
AB  - A single-step TiX4-mediated Prins-type cyclization of cyclopropane carbaldehydes
      with 3-buten-1-ol for the highly stereoselective construction of relatively
      strained ( E)-hexahydrooxonines is reported. Switching the alcohol to 3-butyn-1
      ol prompted a similar route, augmented by another cyclization within a nine
      membered ring to afford a bicyclized product (4,4-dihalo-5
      aryloctahydrocyclopenta[ b]pyran). Easy transformation of the resulting geminal
      dihalide to a vinyl halide and a ketone further supplemented the substance of
      this approach.

PMID- 30110173
TI  - Formal [1 + 2 + 3] Annulation: Domino Access to Carbazoles and Indolocarbazole
      Alkaloids.
AB  - A new formal [1 + 2 + 3] annulation of o-alkenyl arylisocyanides with alpha, beta
      unsaturated ketones under metal-, base-, and acid-free conditions is disclosed.
      This domino reaction provides a general protocol for the efficient and practical
      synthesis of a wide range of carbazole derivatives from readily available
      starting materials in a single operation. Furthermore, this methodology was used
      as the key step in a protecting-group-free synthesis of indolocarbazole alkaloids
      arcyriaflavin A and racemosin B.

PMID- 30110174
TI  - PP2A as a New Player in Chronic Obstructive Pulmonary Disease.

PMID- 30110175
TI  - Fetal undernutrition, placental insufficiency and pancreatic beta-cell
      development programming in utero.
AB  - The prevalence of obesity and type 2 (T2D) diabetes is a major health concern in
      the United States and around the world. T2D is a complex disease characterized by
      pancreatic beta-cell failure in association with obesity and insulin resistance
      in peripheral tissues. Although several genes associated with T2D have been
      identified, it is speculated that genetic variants account for only less than 10%
      of the risk for this disease. A strong body of data from both human
      epidemiological and animal studies shows that fetal nutrient factors in utero
      confer significant susceptibility to T2D. Numerous studies done in animals have
      shown that sub-optimal maternal environment or placental insufficiency causes
      intrauterine growth restriction (IUGR) in the fetus, a critical factor known to
      predispose offspring to obesity and T2D, in part by causing permanent
      consequences in total functional beta-cell mass. This mini-review will focus on
      the contribution of the placenta in fetal programming of obesity and T2D, and its
      likely impact on pancreatic beta-cell development and growth.

PMID- 30110176
TI  - Mechanism of Sodium Balance: Total Body Sodium, Surrogate Variables and Renal
      Sodium Excretion.
AB  - The classical concepts of human sodium balance include (i) a total pool of Na+ of
      ~4200 mmol (total body sodium, TBS) distributed primarily in the extracellular
      fluid (ECV) and bone, (ii) intake variations of 0.03 to ~6 mmol ? (kg body mass ?
      day)-1, (iii) asymptotic transitions between steady states with a halftime (T1/2)
      of 21h, (iii) changes in TBS driven by sodium intake measuring ~1.3 d
      (DeltaTBS/Delta(Na+ intake/d)), (iv) adjustment of Na+ excretion to match any
      diet thus providing metabolic steady state, and (v) regulation of TBS via
      controlled excretion (90-95% renal) mediated by surrogate variables. The present
      focus areas include (i) uneven, non-osmotic distribution of increments in TBS
      primarily in 'skin', (ii) long-term instability of TBS during constant Na+
      intake, and (iii) physiological regulation of renal Na+ excretion primarily by
      neurohumoral mechanisms dependent on ECV rather than arterial pressure. Under
      physiological conditions (i) the non-osmotic distribution of Na+ seems
      conceptually important, but quantitatively ill defined; (ii) long-term variations
      in TBS represent significant deviations from steady state, but the importance is
      undetermined; and (iii) the neurohumoral mechanisms of sodium homeostasis
      competing with pressure natriuresis are essential for systematic analysis of
      short-term and long-term regulation of TBS. Sodium homeostasis and blood pressure
      regulation are intimately related. Real progress is slow and will accelerate only
      through recognition of the present level of ignorance. Non-osmotic distribution
      of sodium, pressure natriuresis, and volume-mediated regulation of renal sodium
      excretion are essential intertwined concepts in need of clear definitions,
      conscious models, and future attention.

PMID- 30110178
TI  - Rapid Advances in PCD Research: A Brief Update for Pulmonologists.

PMID- 30110177
TI  - Mettl14 is required for mouse postimplantation development by facilitating
      epiblast maturation.
AB  - N6-methyladenosine (m6A) is the most prevalent and reversible internal
      modification of mammalian messenger and noncoding RNAs mediated by specific m6A
      writer, reader, and eraser proteins. As an m6A writer, the methyltransferase-like
      3-methyltransferase-like 14 (METTL14)-Wilms tumor 1-associated protein complex
      dynamically regulates m6A modification and plays important roles in diverse
      biologic processes. However, our knowledge about the complete functions of this
      RNA methyltransferase complex, the contributions of each component to the
      methylation, and their effects on different biologic pathways are still limited.
      By using both in vivo and in vitro models, we here report that METTL14 is
      indispensable for postimplantation embryonic development by facilitating the
      conversion from naive to primed state of the epiblast. Depletion of Mettl14 leads
      to conspicuous embryonic growth retardation from embryonic d 6.5, mainly as a
      result of resistance to differentiation, which further leads to embryonic
      lethality early in gestation. Our data highlight the critical function of METTL14
      as an m6A modification regulator in orchestrating early mouse embryogenesis.
      Meng, T.-G., Lu, X., Guo, L., Hou, G.-M., Ma, X.-S., Li, Q.-N., Huang, L., Fan,
      L.-H., Zhao, Z.-H., Ou, X.-H., OuYang, Y.-C., Schatten, H., Li, L., Wang, Z.-B.,
      Sun, Q.-Y. Mettl14 is required for mouse postimplantation development by
      facilitating epiblast maturation.

PMID- 30110179
TI  - Harsh Parenting and Violence Against Children: A Trial with Ultrapoor Families in
      Francophone West Africa.
AB  - Few culturally congruent interventions are available to reduce abusive practices
      in families living in abject poverty in francophone West Africa. This study tests
      the effects of economic intervention-alone and in combination with a family
      focused component-on parenting outcomes and children's reports of violence in
      rural Burkina Faso. Female caregivers and their 10- to 15-year-old children from
      360 ultrapoor families were recruited to participate in a parallel cluster
      randomized control trial with 3 study arms: the waitlist (control) group, the
      economic intervention group (Trickle Up [TU]), and the economic intervention plus
      family coaching group (TU+). Effects were tested using repeated-measures mixed
      effects regressions. At 12 months from baseline, caregivers from the TU+ group
      reported a reduced use of harsh discipline compared to the control group (Cohen's
      d = -0.57, p = .001) and the TU group (d = -0.48, p = .001). Changes were
      maintained at 24 months. TU+ caregivers also expressed more supportive parenting
      attitudes at 12 months compared to the control group (d = 0.39, p = .022) and the
      TU group (d = 0.55, p = .001). Compared to TU caregivers, caregivers in the TU+
      group also reported a better quality of child-parent relationship (d = 0.40, p =
      .041). At 24 months, children in the TU+ group had lower odds of experiencing
      physical (odds ratio = 0.35, p = .050), 95% confidence interval [0.12, 1.00], and
      emotional (odds ratio = 0.52, p = .033), 95% confidence interval [0.28, 0.95],
      violence at home, compared to the control group children. The evidence suggests
      that involving all family members in sessions on child protection in addition to
      economic strengthening strategies can foster supportive parenting environments
      and reduce family violence among children living in ultralevel poverty in West
      Africa.

PMID- 30110180
TI  - Bioenergetic Responses to Mycobacterium tuberculosis: A Step Closer to Developing
      a New Therapy to Treat Tuberculosis in Smokers?

PMID- 30110181
TI  - Firework-Related Eye Trauma in Germany.
AB  - PURPOSE: Firework devices cause high numbers of eye trauma cases each year
      worldwide. These can range from mild conjunctival irritation to devastating loss
      of all vision or the organ itself. A systematic 10-year retrospective monocentric
      case analysis was the main aim of this study. MATERIALS AND METHODS: All firework
      associated eye trauma patients treated in our clinic from 2007 to 2017 were
      grouped for trauma severity and analyzed for influencing factors like age,
      gender, laterality, final visual acuity, and ocular trauma score (OTS). RESULTS:
      Between 2007 and 2017, 165 eyes of 149 patients were treated due to firework
      associated eye trauma at our clinic. The mean patient age was 28.5 +/- 14.4, 116
      patients (78%) were male, 113 (75.8%) were bystanders, 94 right and 71 left eyes
      were treated, and final visual acuity was 0.26 +/- 0.54 logMAR. The causative
      device were bangers in 98 cases (59%), rockets in 54 cases (33%), and sparklers
      in 13 cases (8%). Patients were significantly older (p = 0.026), final visual
      acuity was significantly lower (p < 0.01), and OTS was significantly higher (p <
      0.01) in patients suffering from major eye trauma compared to minor trauma cases.
      CONCLUSIONS: Patients suffering from firework-associated eye trauma are mostly
      young, male, and bystanders. However, severe trauma is more frequent in higher
      age groups, leading to serious consequences. In Germany, more educational efforts
      and prophylaxis concerning eye trauma caused by firework devices are desirable.

PMID- 30110183
TI  - The Relevance of Aboriginal Peer-Led Parent Support: Strengthening the Child
      Environment in Remote Areas.
AB  - This participatory action research study was situated within a larger research
      study, which investigated the development of a peer-led Aboriginal parent support
      program in the remote setting of Halls Creek in Western Australia. The aim of
      this smaller research component was to explore the self-perceived role of home
      visiting peer support workers in this remote area. Participatory Action Research
      methodology was employed, within which eleven Action Learning Sets were used to
      facilitate participant collaboration (n = 8). All participant data was collected
      in focus groups during the Action Learning Sets where culturally appropriate home
      visiting parent support strategies were developed and examined in partnership
      with a child health nurse researcher. Data were analyzed using thematic analysis
      with three themes relating to the peer support workers' self-perceived role being
      identified: Helping parents be strong for their children; Strengthening culture;
      and Facilitating effective communication. These elements support peer support
      worker activities, helping parents to enhance their children's physical and
      psychosocial developmental environment. This research highlights the critical
      emerging role of peer support workers in home visiting family support in a remote
      area of Australia.

PMID- 30110182
TI  - Impact of Cigarette Smoke Exposure on the Lung Fibroblastic Response after
      Influenza Pneumonia.
AB  - Influenza viruses can result in significant lung injury with significant
      morbidity and mortality. In this study, we evaluated the impact of cigarette
      smoke (CS) exposure on the pulmonary fibroblastic response after influenza
      infection. We used a murine model in which animals were exposed to CS or room air
      and subsequently infected with H1N1 influenza virus. Inflammatory and fibrotic
      responses were measured at different time points after influenza infection.
      Primary fibroblasts were isolated from the lungs of mice and their
      characteristics were evaluated. Exposure to CS significantly increased the amount
      of collagen in the lungs of mice infected with influenza virus compared with the
      nonsmoking group at 30 days after infection. Furthermore, the presence of
      fibroblast-specific protein-positive cells increased in the lungs of influenza
      infected mice that were exposed to CS compared with the infection-alone group.
      The smoking group also showed delays in weight recovery and higher cell counts in
      BAL fluid after infection. Active transforming growth factor beta1 levels in BAL
      fluid increased in both groups; however, CS-exposed mice had a later surge in
      active transforming growth factor beta1 (Day 24). Ex vivo cultures of lung
      derived fibroblasts from CS-exposed mice with influenza infection showed rapid
      proliferation, increased expression of alpha-smooth muscle actin-stained stress
      fibers, and higher expression of growth factors compared with fibroblasts from
      room air-exposed lungs after infection. These results suggest that CS exposure
      changes the fibroblastic potential, leading to increased fibrosis after influenza
      infection.

PMID- 30110184
TI  - Application of plasma-combined regeneration technology in managing facial acne
      scars.
AB  - BACKGROUND AND OBJECTIVES: Plasma skin regeneration (PSR) and platelet-rich
      plasma(PRP) have gained popularity in the treatment of acne scars due to their
      efficacy and improved tolerability. The objective of this investigation was to
      evaluate the synergistic effect of PRP plus PSR (plasma-combined regeneration
      technology, PCRT) in managing facial acne scars. METHODS: From March 2015 to June
      2017,a total of 25 cases with facial atrophic acne scars were treated with PCRT
      treatment for three to five times. Treatments were repeated at an interval of 8
      weeks.Treatment parameters were titrated to an immediate end point of moderate
      erythema. The clinical end point for cessation of treatment was the attainment of
      satisfactory clinical results. Results were monitored photographically up to 6
      months after treatment. The efficacy and adverse effects were evaluated by using
      the following outcome parameters: the duration of edema,erythema and crusting;
      the degree of hyperpigmentation, hypopigmentation and scarformation; subjective
      effective rate was evaluated by patients and physicians. RESULTS: 22 of 25
      participants completed the study, and were followed up for 6-12 months. After
      three to five treatments, evaluation by patients showed that the total effective
      rate was 90.91%. Evaluation by two physicians showed that the total effective
      rate was 86.36%. Treatment was well tolerated by all participants. The total
      duration of side effects was 6.7 +/- 1.7 days of edema, 8.1 +/- 2.3 days of
      erythema,6.5 +/- 1.8 days of crusting, respectively. No hyperpigmentation,
      depigmentation, and worsening of scarring were observed by the conclusion of the
      follow-up period. Conclusion: These results provide initial evidence for the
      safety and effectiveness of PCRT as a well-tolerated modality for the treatment
      of acne scars. PCRT is an ideal treatment for facial acne scars with minimal side
      effect..

PMID- 30110185
TI  - Future Directions in Father Inclusion, Engagement, Retention, and Positive
      Outcomes in Child and Adolescent Research.
AB  - Fathers make important and unique contributions to positive child development. In
      spite of these findings, the research literature has lagged in the study of the
      role and impact of fathers on child development and in the development of
      effective approaches and interventions for fathers. Parameters for additional
      study include the inclusion of fathers in treatment outcome studies, the
      engagement of fathers within studies once included, the retention of fathers in
      interventions and studies once engaged, and the appropriate measurement of father
      related outcomes. A systematic review of 64 studies indicated that there is
      evidence that fathers have been included within multiple studies aimed at
      improving parenting but that there are relatively fewer studies of other targeted
      outcomes such as coparenting. A set of recommendations for future directions in
      the next generation of father-focused studies in the child and adolescent
      psychology literature is presented, with an emphasis on improving study of the
      parameters of inclusion, engagement, retention, and measurement of outcomes.

PMID- 30110186
TI  - Anabolic Medications for Muscle Wasting in COPD: Is the Evidence Getting
      Stronger?

PMID- 30110187
TI  - Blood Pressure and Heart Rate Variability in Primary Open-Angle Glaucoma and
      Normal Tension Glaucoma.
AB  - PURPOSE: Vascular dysfunction and ischemia are believed to play an important part
      in the pathogenesis of glaucoma and especially of normal tension glaucoma (NTG).
      The aim of the present study was to analyze the blood pressure (BP) and heart
      rate variability patterns in patients with primary open-angle glaucoma (POAG) and
      NTG compared with controls. METHODS: In total, 37 patients with POAG, 27 patients
      with NTG, and 82 control subjects were included in a prospective clinical
      validation study. Continuous BP and heart rate were simultaneously recorded over
      30 min (Glaucoscreen, aviant GmbH, Jena, Germany) under resting conditions. Time
      series of heart rate, systolic blood pressure (SBP) and diastolic blood pressure
      (DBP) were extracted and analyzed calculating univariate linear (time domain,
      frequency domain), nonlinear (symbolic dynamics), and bivariate (joint symbolic
      dynamics) indices. RESULTS: Overall, 12 parameters could be identified that were
      significantly different when comparing POAG patients and controls, whereas 80
      parameters were significantly different in NTG patients compared with controls.
      The optimum set consisting of three indices showed a sensitivity of 81.5% at a
      specificity of 86.6% for NTG patients compared with a sensitivity of 62.2% at a
      specificity of 82.9% for POAG patients. CONCLUSIONS: Alterations in BP
      variability and coupling with heart rate suggest impaired patterns of autonomic
      cardiovascular regulation in glaucoma patients especially in patients with NTG.

PMID- 30110188
TI  - The farm level economic and environmental contribution of Intacta soybeans in
      South America: the first five years.
AB  - This study assesses the economic and environmental impacts that have arisen from
      the adoption and use of genetically modified (GM) herbicide tolerant (HT) and
      insect resistant (IR) soybeans in South America in the five years since first
      planted in 2013/14. A total of 73.6 million hectares have been planted to
      soybeans containing these traits since 2013/14, with farmers benefiting from an
      increase in income of $7.64 billion. For every extra $1 spent on this seed
      relative to conventional seed, farmers have gained an additional $3.88 in extra
      income. These income gains have arisen from a combination of higher yields (+
      9.2% across the four countries using the technology) and lower costs of weed and
      pest control. The seed technology has reduced pesticide spraying by 10.44 million
      kg (-15.1%) and, as a result, decreased the environmental impact associated with
      herbicide and insecticide use on these crops (as measured by the indicator, the
      Environmental Impact Quotient (EIQ)) by 30.6%. The technology has also
      facilitated important cuts in fuel use and tillage changes, resulting in a
      significant reduction in the release of greenhouse gas emissions from the GM
      cropping area. In 2017/18, this was equivalent to removing 3.3 million cars from
      the roads.

PMID- 30110189
TI  - A Case of Neurologically Intact Survival after 2 hours and 50 minutes of
      Euthermic Cardiac Arrest Treated with Mechanical CPR and Intra-arrest
      Percutaneous Coronary Intervention.
AB  - We report a case of a 56 year old male in ventricular fibrillation (VF) cardiac
      arrest for a total of 2 hours and 50 minutes who was diagnosed with ST elevation
      myocardial infarction (STEMI) during a brief 10 min period of return of
      spontaneous circulation (ROSC). The patient underwent successful percutaneous
      coronary intervention (PCI) while receiving mechanical chest compressions for
      ongoing VF. Our case demonstrates the potential for neurologically intact
      survival in VF cardiac arrest patients despite prolonged periods of VF who are
      treated with mechanical CPR and intra-arrest PCI.

PMID- 30110190
TI  - Association between Skin Thickness Measurements with Corneal Biomechanical
      Properties and Dry Eye Tests in Systemic Sclerosis.
AB  - PURPOSE: To analyse the association between skin score with corneal biomechanics
      and dry eye tests in systemic sclerosis (SSc). METHODS: 112 cases (limited SSc
      (lcSSc), n=50; diffuse SSc  (dcSSc), n=32; controls, n=30) were included in the
      study. Corneal hysteresis (CH), corneal resistance factor (CRF), Schirmer 1, 2
      tests, OSDI score and modified Rodnan skin score (mRSS) were evaluated. RESULTS:
      There was correlation between the mRSS and CH (p = 0.004, r = -0.402; p < 0.001,
      r = -0.786, respectively) as well as correlation with the CRF (p < 0.001, r =
      0.709; p < 0.001, r = 0.848, respectively) and OSDI (p < 0.001, r = 0.74; p <
      0.001, r = 0.89, respectively) score in lcSSc and dcSSc. Also, the Schirmer 1 (p
      < 0.001, r = -0.802) and 2 (p < 0.001, r = -0.587) test values showed correlation
      with the mRSS in dcSSc. CONCLUSION: Skin score had clinically significant
      importance for predicting corneal biomechanical properties and dry eye tests in
      both lcSSc and dcSSc.

PMID- 30110191
TI  - Silence is golden: gene silencing of V. cholerae during intestinal colonization
      delivers new aspects to the acid tolerance response.
AB  - Bacterial pathogens of the gastrointestinal tract alter their expression profile
      upon ingestion by the host and activate a variety of factors enhancing
      colonization and virulence. However, gene silencing during infection might be as
      important as gene activation to achieve full colonization fitness. Thus, we
      developed and successfully applied a reporter technology to identify 101 in vivo
      repressed (ivr) genes of the bacterial pathogen Vibrio cholerae. In depth
      analysis of the in vivo repressed H+/Cl- transporter ClcA revealed an inverse
      requirement along gastrointestinal colonization. ClcA could be linked to acid
      tolerance response required during stomach passage, but ClcA expression is
      detrimental during subsequent colonization of the lower intestinal tract as it
      exploits the proton-motive force in alkaline environments. The study summarized
      in this addendum demonstrates that constitutive expression of ivr genes can
      reduce intestinal colonization fitness of V. cholerae, highlighting the necessity
      to downregulate these genes in vivo.

PMID- 30110192
TI  - Successful maintenance therapy with apatinib inplatinum-resistant advanced
      ovarian cancer and literature review.
AB  - Ovarian cancer is a most common lethal gynecological malignant tumor, with a
      gradual increasing incidence throughout the world. The mainstay treatment is
      cytoreductive surgery followed by platinum-based chemotherapy. However, a high
      percentage of patients recur, thus needing multiple treatments with a frequently
      poor prognosis. Apatinib is a novel and highly selective tyrosine kinase
      inhibitor of vascular endothelial growth factor receptor-2. Previous studies have
      suggested that apatinib is safe and effective in some solid tumors. We report one
      case with platinum-resistant advanced epithelial ovarian cancer, who had failed
      prior treatment with multiple chemotherapy reagents. She was negative for
      multiple driver genes including BRCA1/2,EGFR,KRAS/NRAS/BRAF, ALK, HER2 and cMET.
      Five courses of apatinib plus epirubicin were given. Due to the heavy
      leukothrombopenia, apatinib monotherapy, at 250 mg qd dose level, was used for
      maintenance therapy. The progression-free survival (PFS) time was 12.6 months.
      After that, the disease was slightly progressive during apatinib maintenance and
      then entered into a "stable" state until now. It indicated that apatinib may be a
      superior choice for advanced ovarian cancer patients, but further prospective
      studies are needed to optimize the treatment.

PMID- 30110193
TI  - Does fibrin(ogen) bind to monomeric or dimeric GPVI, or not at all?
AB  - GPVI is the major signalling receptor for collagen on platelets. Dimerization of
      GPVI is required for collagen binding and initiation of signalling through the
      associated FcR-gamma chain. Recently, fibrin and fibrinogen have been identified
      as ligands for GPVI and shown to induce signalling in support of thrombus
      formation and stabilization. Contrasting observations have been reported on
      whether fibrin binds to monomeric or dimeric GPVI, or to neither form. In this
      article, we discuss reasons for the contradictory results and how to reconcile
      these. We conclude that a lack of structural knowledge regarding the GPVI
      constructs that are being used, along with the use of non-standardized reagents,
      might be the main cause of the discrepant results. This article aims to highlight
      some of the key areas that need to be addressed.

PMID- 30110195
TI  - Cyber-Physical Systems: When the Embedded World Meets the Virtual World.

PMID- 30110194
TI  - CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus
      Ipilimumab in Patients With Metastatic Esophagogastric Cancer.
AB  - PURPOSE: Metastatic esophagogastric cancer treatments after failure of second
      line chemotherapy are limited. Nivolumab demonstrated superior overall survival
      (OS) versus placebo in Asian patients with advanced gastric or gastroesophageal
      junction cancers. We assessed the safety and efficacy of nivolumab and nivolumab
      plus ipilimumab in Western patients with chemotherapy-refractory esophagogastric
      cancers. PATIENTS AND METHODS: Patients with locally advanced or metastatic
      chemotherapy-refractory gastric, esophageal, or gastroesophageal junction cancer
      from centers in the United States and Europe received nivolumab or nivolumab plus
      ipilimumab. The primary end point was objective response rate. The association of
      tumor programmed death-ligand 1 status with response and survival was also
      evaluated. RESULTS: Of 160 treated patients (59 with nivolumab 3 mg/kg, 49 with
      nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, 52 with nivolumab 3 mg/kg plus
      ipilimumab 1 mg/kg), 79% had received two or more prior therapies. At the data
      cutoff, investigator-assessed objective response rates were 12% (95% CI, 5% to
      23%), 24% (95% CI, 13% to 39%), and 8% (95% CI, 2% to 19%) in the three groups,
      respectively. Responses were observed regardless of tumor programmed death-ligand
      1 status. With a median follow-up of 28, 24, and 22 months across the three
      groups, 12-month progression-free survival rates were 8%, 17%, and 10%,
      respectively; 12-month OS rates were 39%, 35%, and 24%, respectively. Treatment
      related grade 3/4 adverse events were reported in 17%, 47%, and 27% of patients
      in the three groups, respectively. CONCLUSION: Nivolumab and nivolumab plus
      ipilimumab demonstrated clinically meaningful antitumor activity, durable
      responses, encouraging long-term OS, and a manageable safety profile in patients
      with chemotherapy-refractory esophagogastric cancer. Phase III studies evaluating
      nivolumab or nivolumab plus ipilimumab in earlier lines of therapy for
      esophagogastric cancers are underway.

PMID- 30110196
TI  - Analyzing College Students' Social Media Communication Apprehension.
AB  - Research has shown that college students are heavy users of social media. Yet,
      very little has looked at the connection between college students' social media
      use and communication apprehension (CA). Due to the shortage of research
      concerning CA and social media, this study aims to test the relationship between
      social media CA and introversion in relationship to social media use and social
      media addiction. To test these relationships, 396 undergraduate students were
      surveyed. The survey consisted of instruments used to measure the individuals'
      levels of social media use, social media addiction, introversion, and CA. After
      conducting multiple linear regressions, it was determined that there was a
      negative relationship between social media CA and introversion with (1) social
      media use and (2) social media addiction. Results indicated that social media CA
      was significantly related to social media addiction. These findings suggest that
      college students might gravitate toward social media to communicate rather than
      face-to-face communication.

PMID- 30110197
TI  - MOVING BEYOND: Age-Related Motor Deficits.

PMID- 30110198
TI  - Problematic Video Gaming and Problematic Internet Use Among Polish Young Adults.
AB  - Technological advancements, on the one hand, facilitate everyday activities and,
      on the other hand, may lead to problematic behavior. These include problematic
      video gaming (PVG) and problematic Internet use. The purpose of this article is
      to present the specificity of these behavioral addictions in a group of Polish
      young adults and to determine their predictors and interrelatedness. The study
      involved a group of 1,493 young adults, aged from 18 to 30. The intensity of
      problematic Internet use was measured with the Problematic Internet Use Test (the
      Polish version of Internet Addiction Test developed by Kimberly Young), and
      intensity of PVG was measured with the Problem Video Game Playing Questionnaire.
      Based on the results, it can be shown that in the group of Polish young adults
      participating in the study, 0.3 percent of the individuals present very high
      problematic Internet use. On the contrary, 3.6 percent of the gamers show signs
      of PVG. Furthermore, analysis of structural equations showed that only the model
      assuming a correlation between the two types of behavioral addiction correctly
      fits the data set. Based on the developed model, it was established that the
      duration of social network usage is probably a predictor of problematic Internet
      use, while predictors of PVG include the amount of time dedicated to playing
      video games as well as engagement in action games. The present findings enable
      better understanding of the relationship between PVG and problematic Internet use
      among young adults. They also support other studies which suggest that, despite
      similarities between them, various types of behavioral addictions may be
      predicted by different factors.

PMID- 30110199
TI  - "Alexa, Are You My Mom?" The Role of Artificial Intelligence in Child
      Development.

PMID- 30110200
TI  - Psychometric Properties of the Internet Addiction Test: A Systematic Review and
      Meta-Analysis.
AB  - This article performs a systemic review of psychometric properties of Internet
      Addiction Test (IAT)-the most widely used tool for assessing Internet addiction
      in clinic and research field. Studies measuring psychometric properties of IAT
      (original version) were searched through MEDLINE, The Cumulative Index to Nursing
      and Allied Health Literature (CINAHL), PsycINFO, and Embase. A total of 25
      studies including 18,421 subjects were reviewed in our study. Based on meta
      analysis for internal consistency, the pooled Cronbach's alpha coefficient from
      college/university students with a single department subgroup was 0.90 (95percent
      confidence interval [CI], 0.89-0.91), and that from middle-/high-school students
      (older than 15 years) subgroup was 0.93 (95 percent CI, 0.92-0.93). According to
      test-retest analysis, the pooled Spearman's correlation coefficient from
      college/university students with a single department subgroup was high at 0.83
      (95 percent CI, 0.81-0.85), along with low publication bias. Convergent validity
      showed correlation coefficients of 0.62-0.84, as compared with major tools. For
      construct validity, the number of factors is believed to be 1-2, only considering
      studies that followed the guidelines. IAT appears to have acceptable internal
      consistency, test-retest reliability, and convergent validity in specific groups.
      To verify these values, well-designed evidence-based studies assessing
      psychometric properties of IAT across diverse populations are warranted.

PMID- 30110201
TI  - Economic models for sustainable interprofessional education.
AB  - Limited information exists on funding models for interprofessional education
      (IPE) course delivery, even though potential savings from IPE could be gained in
      healthcare delivery efficiencies and patient safety. Unanticipated economic
      barriers to implementing an IPE curriculum across programs and schools in
      University settings can stymie or even end movement toward collaboration and
      sustainable culture change. Clarity among stakeholders, including institutional
      leadership, faculty, and students, is necessary to avoid confusion about IPE
      tuition costs and funds flow, given that IPE involves multiple schools and
      programs sharing space, time, faculty, and tuition dollars. In this paper, we
      consider three funding models for IPE: (a) Centralized (b) Blended, and (c)
      Decentralized. The strengths and challenges associated with each of these models
      are discussed. Beginning such a discussion will move us toward understanding the
      return on investment of IPE.

PMID- 30110202
TI  - Direct comparison of the abilities of bone marrow mesenchymal versus
      hematopoietic stem cells to reverse hyperglycemia in diabetic NOD.SCID mice.
AB  - Both bone marrow-derived hematopoietic stem cells (HSC) and mesenchymal stem
      cells (MSC) improve glycemic control in diabetic mice, but their kinetics and
      associated changes in pancreatic morphology have not been directly compared. Our
      goal was to examine the time course of improvements in glucose tolerance and
      associated changes in beta-cell mass and proliferation following transplantation
      of equivalent numbers of HSC or MSC from the same bone marrow into diabetic non
      obese diabetic severe combined immune deficiency (NOD.SCID) mice. We used
      transgenic mice with a targeted expression of yellow fluorescent protein (YFP)
      driven by the Vav1 gene promoter to genetically tag HSC and progeny. HSC were
      separated from bone marrow by fluorescence-activated cell sorting and MSC
      following cell culture. Equivalent numbers of isolated HSC or MSC were
      transplanted directly into the pancreas of NOD.SCID mice previously made diabetic
      with streptozotocin. Glucose tolerance, serum insulin, beta-cell mass and beta
      cell proliferation were examined up to 28 days following transplant.
      Transplantation with MSC improved glucose tolerance within 7 days and serum
      insulin levels increased, but with no increase in beta-cell mass. Mice
      transplanted with HSC showed improved glucose tolerance only after 3 weeks
      associated with increased beta-cell proliferation and mass. We conclude that
      single injections of either MSC or HSC transiently improved glycemic control in
      diabetic NOD.SCID mice, but with different time courses. However, only HSC
      infiltrated the islets and were associated with an expanded beta-cell mass. This
      suggests that MSC and HSC have differing mechanisms of action.

PMID- 30110203
TI  - Erucamide from Radish Leaves Has an Inhibitory Effect Against
      Acetylcholinesterase and Prevents Memory Deficit Induced by Trimethyltin.
AB  - In this study, we investigated a potent acetylcholinesterase inhibitor that was
      isolated from radish leaf (Raphanus sativus L.) extracts. Through sequential
      fractionation of radish leaf extract, the active constituent was identified as
      cis-13-docosenamide (erucamide). To validate the potency, erucamide derived from
      radish leaves was supplemented in diets and then fed to trimethyltin (TMT)
      exposed mice. Specifically, mice had free access to a control diet or diets
      containing different concentrations of erucamide for 3 weeks, followed by an
      injection of TMT (2.5 mg/kg body weight). Our results showed that pretreatment of
      mice with erucamide (20 and 40 mg/kg body weight per day) significantly
      attenuated the TMT-induced learning and memory deficits that were assessed by Y
      maze and passive avoidance tests. These findings suggest that radish leaves, and
      possibly its isolated erucamide, may have preventive effects against memory
      deficits related to Alzheimer's disease by modulation of cholinergic functions.

PMID- 30110205
TI  - What Is Your Neurologic Diagnosis?

PMID- 30110204
TI  - Notoginseng Radix and Rehmanniae Radix Preparata Extract Combination (YH23537)
      Reduces Pain and Cartilage Degeneration in Rats with Monosodium Iodoacetate
      Induced Osteoarthritis.
AB  - Notoginseng Radix and Rehmanniae Radix Preparata have been widely used
      traditionally for treating inflammatory diseases. This research studies the
      therapeutic effects of YH23537, the extracts of Notoginseng Radix and Rehmanniae
      Radix Preparata, on pain and cartilage degeneration in an experimental
      osteoarthritis (OA) model. Male Wistar rats were inoculated intra-articularly
      with 3 mg of monosodium iodoacetate (MIA) in the right intra-articular. Four days
      later, the animals were administrated orally with YH23537 daily for 24 days.
      Tactile allodynia and weight bearing were measured. Macroscopic and microscopic
      observations for articular cartilage were performed at the end of the experiment.
      Protein expression in the joint was determined by immunohistochemistry. The
      effects of YH23537 on mRNA levels in chondrocytes stimulated with interleukin
      (IL)-1beta were analyzed using random polymerase chain reaction. OA induction was
      confirmed by significant decrease of paw withdrawal latency, paw withdrawal
      threshold, and weight bearing compared with the normal group at 3 days after MIA
      injection. The YH23537-treated groups displayed significant increases in pain
      thresholds and weight bearing throughout the observation period. The damage to
      articular cartilage was significantly lessened visually and histopathologically
      by YH23537 treatment. YH23537 suppressed the expression of metalloproteinase-3,
      nitrotyrosine, IL-1beta and IL-6 increased in OA joints. YH23537 upregulated
      tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3 in IL-1beta-stimulated
      human OA chondrocytes. The protein levels of the NF-kappaBp65 and HIF-2alpha in
      the joint tissues were reduced by YH23537. YH23537 exerted antinociceptive
      effects and cartilage protective effects in experimental OA rats by suppressing
      oxidative injury, inflammatory mediators, and inducing anabolic factors. We
      suggest that YH23537 may have efficacy for treating OA in humans.

PMID- 30110206
TI  - Cost of bovine respiratory disease in preweaned calves on US beef cow-calf
      operations (2011-2015).
AB  - OBJECTIVE To develop a partial budget analysis of direct costs associated with
      bovine respiratory disease (BRD) in preweaned calves on US beef cow-calf
      operations and identify factors that strongly influence those costs. DESIGN Risk
      analysis model. ANIMALS US preweaned beef calf inventory from 2011 through 2015.
      PROCEDURES A stochastic simulation model was developed by use of a computer
      spreadsheet and add-in software. Input data were obtained from the USDA, peer
      reviewed literature, and a survey of beef cow-calf producers. A simulation
      consisting of 10,000 iterations was used to account for either uncertainty or
      variability in model inputs. The median (90% confidence interval) was reported
      for each output variable. Global and local sensitivity analyses were performed to
      identify the most influential factors and quantitatively evaluate the effects of
      inputs on the estimated costs. RESULTS From 2011 through 2015, BRD in preweaned
      calves cost the US beef cow-calf industry approximately $165 million annually, of
      which costs associated with the death, treatment, and decreased weaning weight of
      BRD-affected calves were approximately $126, $25, and $15 million, respectively.
      CONCLUSIONS AND CLINICAL RELEVANCE Although BRD in preweaned calves may have a
      fairly small effect on the total gross income for the US beef cow-calf industry
      as a whole, it can have a substantial adverse effect on the net profit of BRD
      affected herds. The model developed provided important information regarding the
      cost of BRD in preweaned calves on US beef cow-calf operations and identified
      factors that had an import effect on those costs.

PMID- 30110207
TI  - Speaking up and making our voice heard.

PMID- 30110208
TI  - Assessment of the effects of gabapentin on activity levels and owner-perceived
      mobility impairment and quality of life in osteoarthritic geriatric cats.
AB  - OBJECTIVE Toevaluate effects of gabapentin on activity levels and owner-perceived
      mobility impairment and quality of life (QOL) in osteoarthritic geriatric cats.
      DESIGN Blinded, placebo-controlled, randomized crossover-design study. ANIMALS 20
      osteoarthritic cats (>= 10 years old). PROCEDURES Cats received gabapentin (10
      mg/kg [4.5 mg/lb]) or placebo treatment, PO, every 12 hours for 2 weeks, followed
      by the alternate treatment (with no washout period). Activity was assessed with a
      collar-mounted accelerometer. A client-specific outcome measure (CSOM)
      questionnaire was used weekly to collect owner assessments of 3 selected
      activities in which their cats had impaired mobility; QOL ratings (worse, the
      same, or improved) following crossover to each treatment and for the overall
      study period were collected at the end of the investigation. Activity counts,
      CSOM and QOL data, and deterioration in impaired activities (ie, decrease of >= 2
      points in CSOM scores) associated with treatment crossover were assessed
      statistically. Adverse events were recorded. RESULTS Gabapentin administration
      was associated with significantly lower mean daily activity counts (48,333 vs
      39,038 counts/d) and significantly greater odds (approx 3-fold change) of CSOM
      ratings indicating improvement in impaired activities, compared with results for
      the placebo treatment. A greater proportion of cats had deterioration in impaired
      activities after the crossover from gabapentin to placebo than when the opposite
      occurred, but the proportion of cats with worsened QOL did not differ between
      sequences. Adverse events were noted for 10 cats (9 that completed the study)
      during gabapentin treatment (sedation, ataxia, weakness, and muscle tremors) and
      1 cat during placebo treatment (lethargy). CONCLUSIONS AND CLINICAL RELEVANCE
      Gabapentin treatment was associated with improvement in owner-identified impaired
      activities of osteoarthritic cats. Activity levels were lower than those during
      placebo treatment, and sedation was the most common adverse effect.

PMID- 30110210
TI  - In This Issue * September 1, 2018.

PMID- 30110209
TI  - Pathology in Practice.

PMID- 30110211
TI  - Synostosis of the first and second ribs in six horses.
AB  - CASE DESCRIPTION Over a 2-year period, 6 horses (4 Selle Francais, 1 Hanoverian,
      and 1 Thoroughbred) were referred for evaluation of forelimb lameness. All horses
      had radiographic evidence of synostosis of the first and second ribs (SFSR).
      CLINICAL FINDINGS For 1 horse, the SFSR was considered the probable cause of the
      lameness (grade 3/5), with a shortening of the cranial phase of the stride in the
      affected limb. For 3 horses, it was considered a possible cause of the lameness
      (grade 1/5) for the same reason. For 2 horses, SFSR was considered an incidental
      finding unassociated with any clinical signs. The 4 horses with lameness
      suspected as attributable to SFSR had a moderate to severe amount of irregularly
      marginated new bone formation at the site of the SFSR, with a cranial
      displacement of the first rib, compared with findings for the 2 horses in which
      the SFSR was considered incidental. A likely congenital abnormality of the first
      rib was first suspected on nuclear scintigraphy in the 1 horse for which it was
      performed or on radiography of the caudal cervical portion of the vertebral
      column (3 horses) or shoulder joint (2 horses). TREATMENT AND OUTCOME The horse
      in which SFSR was considered the probable cause of the lameness was retired to
      the field and remained chronically lame. Two of the 3 horses in which SFSR was
      considered a possible cause of lameness received an IV infusion of tiludronate
      disodium and mesotherapy over the caudal cervical and cranial thoracic regions;
      both returned to competition but with poor results. One of the 2 horses with
      subclinical SFSR never developed lameness on the affected side. No follow-up
      information was available for the other 2 horses. CLINICAL RELEVANCE SFSR can be
      an incidental finding in horses, with or without clinical manifestations. This
      abnormality should be considered as a differential diagnosis for horses with
      forelimb lameness and associated shortening of the cranial phase of the stride
      that fails to improve with diagnostic analgesic techniques.

PMID- 30110212
TI  - Acute masticatory muscle compartmental syndrome in a dog.
AB  - CASE DESCRIPTION A5.5-year-old sexually intact male Bull Terrier was referred for
      evaluation because of sudden facial swelling and an inability to close its mouth.
      CLINICAL FINDINGS Physical examination revealed bilaterally elevated nictitating
      membranes, an inability to adduct the mandible without assistance, and severe,
      diffuse, firm masticatory muscle swelling. Computed tomographic examination of
      the head revealed symmetric bilateral enlargement of the temporalis, masseter,
      and pterygoid muscles with heterogeneous contrast enhancement. Intracompartmental
      pressures in the left and right temporalis muscles as measured with an invasive
      arterial blood pressure transducer were 72 and 96 mm Hg, respectively. TREATMENT
      AND OUTCOME Emergent fasciotomy of the temporalis and masseter muscles was
      performed, followed by medical management with corticosteroids and analgesics.
      The diffuse facial swelling resolved within 1 week after surgery. Results of
      serologic testing for antibody against masticatory 2M muscle fibers were
      negative. Results of histologic examination of temporalis muscle specimens were
      consistent with mild to moderate multifocal neutrophilic and histiocytic myositis
      with myofiber degeneration and necrosis. CLINICAL RELEVANCE Acute compartmental
      syndrome should be considered as a differential diagnosis for dogs with a sudden
      onset of severe skeletal muscle swelling, signs of pain, and dysfunction.
      Findings for this dog with acute compartmental syndrome isolated to the
      masticatory muscles suggested that emergent fasciotomy followed by medical
      management may be an effective technique for treatment of this rare disease in
      dogs.

PMID- 30110213
TI  - Beef producer survey of the cost to prevent and treat bovine respiratory disease
      in preweaned calves.
AB  - OBJECTIVE To estimate costs associated with prevention and treatment of bovine
      respiratory disease (BRD) in preweaned calves on US beef cow-calf operations.
      DESIGN Cross-sectional survey. SAMPLE 43 beef cow-calf producers whose operations
      had a history of BRD in preweaned calves. PROCEDURES Mail and electronic surveys
      were developed and administered to producers in Nebraska, North Dakota, and South
      Dakota to obtain information regarding costs of BRD prevention and treatment.
      Descriptive statistics were generated. Mixed linear regression models were used
      to assess factors associated with the costs of vaccines, medicine, and labor and
      percentage time spent on prevention and treatment of BRD in cows, replacement
      heifers, and preweaned calves. RESULTS 7 mail and 36 electronic surveys were
      completed. Median annual costs for BRD vaccines were $2.25, $4.00, and
      $6.25/animal, and median annual labor costs for vaccination were $4.58, $3.00,
      and $5.00/animal for cows, heifers, and preweaned calves, respectively. Median
      annual costs for medicine and labor to treat preweaned calves for BRD were $11.00
      and $15.00/ affected calf, respectively. Adjusted mean annual BRD vaccine cost
      for preweaned calves ($7.67/animal) was significantly greater than that for cows
      ($3.18/animal) and heifers ($4.48/animal). CONCLUSIONS AND CLINICAL RELEVANCE
      Results indicated that labor costs associated with BRD vaccination and treatment
      were similar to or exceeded the cost of vaccines and medicine, and most of those
      labor costs were associated with gathering and sorting cattle. Therefore, costs
      associated with labor as well as medicine and vaccines should be considered
      during the development of BRD prevention and treatment plans.

PMID- 30110215
TI  - Information for veterinarians on reporting suspected animal food issues.

PMID- 30110216
TI  - Nutritional management of chronic enteropathies in dogs and cats.

PMID- 30110217
TI  - What Is Your Diagnosis?

PMID- 30110218
TI  - Factors associated with survival to hospital discharge for cats treated
      surgically for thoracic trauma.
AB  - OBJECTIVE To determine the most common types of injuries in cats surgically
      treated for thoracic trauma, complications associated with surgical treatment,
      and factors associated with mortality rate and evaluate the effectiveness of the
      animal trauma triage (ATT) scoring system for predicting outcome. DESIGN
      Retrospective case series with nested observational study. ANIMALS 23 client
      owned cats surgically treated for thoracic trauma at 7 veterinary teaching
      hospitals between 1990 and 2014. PROCEDURES Medical records were reviewed to
      collect data on signalment, medical history, clinical signs and physical
      examination findings at initial evaluation, clinicopathologic findings, initial
      emergency treatments and diagnostic tests performed, type of trauma sustained,
      imaging findings, surgery details, postoperative complications, duration of
      hospitalization, and cause of death, if applicable. All variables were evaluated
      for associations with survival to hospital discharge. RESULTS Types of trauma
      that cats had sustained included dog bite or attack (n = 8 [35%]), motor vehicle
      accident (6 [26%]), other animal attack (2 [9%]), impalement injury or fall (2
      [9%]), projectile penetrating trauma (1 [4%]), or unknown origin (4 [17%]).
      Intrathoracic surgery was required for 65% (15/23) of cats. The overall
      perioperative mortality rate was 13% (3/23). Mean +/- SD ATT scores for surviving
      and nonsurviving cats were 6.4 +/- 2.2 and 10.0 +/- 1.7, respectively. Nineteen
      of 20 cats with no cardiopulmonary arrest survived to discharge, compared with 1
      of 3 cats with cardiopulmonary arrest. Only these 2 variables were significantly
      associated with outcome. CONCLUSIONS AND CLINICAL RELEVANCE The perioperative
      mortality rate was low in this series of cats with thoracic trauma; however,
      those with cardiopulmonary arrest were less likely to survive to hospital
      discharge than other cats. Cats with a low ATT score were more likely to survive
      than cats with a high ATT score.

PMID- 30110219
TI  - Results of a survey of Veterinary Orthopedic Society members on the preferred
      method for treating cranial cruciate ligament rupture in dogs weighing more than
      15 kilograms (33 pounds).
AB  - OBJECTIVE To determine which method (lateral fabellotibial suture [LFS], tibial
      plateau leveling osteotomy [TPLO], tibial tuberosity advancement [TTA], or
      tightrope-like braided multifilament suture secured with metallic buttons [TR])
      Veterinary Orthopedic Society (VOS) members preferred for treating cranial
      cruciate ligament rupture (CCLR) in dogs weighing > 15 kg (33 lb), identify
      factors associated with this preference, and assess concerns related to surgical
      implant material used. DESIGN Cross-sectional study. SAMPLE 187 VOS members.
      PROCEDURES All registered VOS members received an online survey from June to July
      2016. Responses were compiled and evaluated for associations with method
      preferences and perceived complications. RESULTS Overall response rate was 38.4%
      (221/575). Respondents had graduated from veterinary school a mean of 23 years
      prior to survey completion, and collectively they performed approximately 30,000
      CCLR surgeries annually. The most commonly preferred method was TPLO (147
      [78.6%]), followed by TTA (26 [13.9%]), the LFS procedure (11 [5.9%]), and the TR
      procedure (3 [1.6%]). The preference for TPLO was independent of board
      certification or college of training (American, European, or other College of
      Veterinary Surgeons). Non-board-certified surgeons, including general
      practitioners, also favored TPLO. The most common perceptions were that titanium
      implants (used for TTA) were associated with the lowest incidence of major
      complications, whereas braided multifilament suture (used for the TR procedure)
      was associated with the highest incidence of major complications. CONCLUSIONS AND
      CLINICAL RELEVANCE Results suggested that TPLO was preferred for treating CCLR in
      dogs weighing > 15 kg and that the TR procedure was perceived as having the
      highest complication rate. With results of this survey in mind, use of the TR
      procedure should be considered cautiously when treating CCLR.

PMID- 30110220
TI  - Pathology in Practice.

PMID- 30110222
TI  - Cancer Care After the 2017 Central Mexico Earthquake.

PMID- 30110223
TI  - ASCO Resource-Stratified Guidelines: Methods and Opportunities.
AB  - The objectives of this article are to describe the ASCO Resource-Stratified
      Guidelines and to provide background within the context of ASCO Guidelines and
      efforts to address the global cancer burden.

PMID- 30110224
TI  - Multiprofessional Ward Rounds for Inpatients With Advanced Cancers: Too Big to
      Succeed?

PMID- 30110221
TI  - Retrospective Validation and Clinical Implementation of Automated Contouring of
      Organs at Risk in the Head and Neck: A Step Toward Automated Radiation Treatment
      Planning for Low- and Middle-Income Countries.
AB  - Purpose We assessed automated contouring of normal structures for patients with
      head-and-neck cancer (HNC) using a multiatlas deformable-image-registration
      algorithm to better provide a fully automated radiation treatment planning
      solution for low- and middle-income countries, provide quantitative analysis, and
      determine acceptability worldwide. Methods Autocontours of eight normal
      structures (brain, brainstem, cochleae, eyes, lungs, mandible, parotid glands,
      and spinal cord) from 128 patients with HNC were retrospectively scored by a
      dedicated HNC radiation oncologist. Contours from a 10-patient subset were
      evaluated by five additional radiation oncologists from international partner
      institutions, and interphysician variability was assessed. Quantitative agreement
      of autocontours with independently physician-drawn structures was assessed using
      the Dice similarity coefficient and mean surface and Hausdorff distances.
      Automated contouring was then implemented clinically and has been used for 166
      patients, and contours were quantitatively compared with the physician-edited
      autocontours using the same metrics. Results Retrospectively, 87% of normal
      structure contours were rated as acceptable for use in dose-volume-histogram
      based planning without edit. Upon clinical implementation, 50% of contours were
      not edited for use in treatment planning. The mean (+/- standard deviation) Dice
      similarity coefficient of autocontours compared with physician-edited
      autocontours for parotid glands (0.92 +/- 0.10), brainstem (0.95 +/- 0.09), and
      spinal cord (0.92 +/- 0.12) indicate that only minor edits were performed. The
      average mean surface and Hausdorff distances for all structures were less than
      0.15 mm and 1.8 mm, respectively. Conclusion Automated contouring of normal
      structures generates reliable contours that require only minimal editing, as
      judged by retrospective ratings from multiple international centers and clinical
      integration. Autocontours are acceptable for treatment planning with no or, at
      most, minor edits, suggesting that automated contouring is feasible for clinical
      use and in the ongoing development of automated radiation treatment planning
      algorithms.

PMID- 30110225
TI  - Patient- and Hospital-Level Factors Associated With Readmission for Malignant
      Pleural Effusion.
AB  - PURPOSE: Readmission after hospitalization for malignant pleural effusion (MPE)
      may represent gaps in the quality of health care delivery. The goal of this study
      was to determine the frequency of 30-day readmission for MPE and identify
      clinical factors associated with rehospitalization. PATIENTS AND METHODS: A
      retrospective cohort of adults hospitalized for MPE from 2009 to 2011 was
      analyzed using an administrative database. The primary outcome was all-cause 30
      day readmission rate. Hierarchic mixed-effects logistic regression models were
      used to examine associations between patient- and hospital-level factors and 30
      day readmission and assess variation in readmission rates across hospitals.
      RESULTS: The 7-, 14-, 30-, 60-, and 90-day readmission rates for MPE were 16.1%,
      25.9%, 38.3%, 52.5%, and 63.8%, respectively. The most common primary diagnoses
      for 30-day readmission were MPE (69.5%) and other clinical issues related to
      malignancy (21.1%). Clinical factors associated with 30-day readmission were
      female sex (odds ratio [OR], 0.78; 95% CI, 0.63 to 0.95), greater number of
      medical comorbidities (OR, 1.51; 95% CI, 1.15 to 1.99), and having a do-not
      resuscitate order (OR, 1.37; 95% CI, 1.03 to 1.84). Hospitals in the 90th
      percentile were only 1.1 times more likely to have a 30-day readmission for MPE
      than those in the lowest 10th percentile (40.9% v 37%). CONCLUSION: Readmission
      for MPE is common and frequently results from progression of malignancy.
      Readmission rates were similar across all hospitals, suggesting they are unlikely
      to be mutable using conventional approaches to reduce rehospitalizations.
      Instead, interventions may need to focus on addressing care planning at the end
      of life.

PMID- 30110226
TI  - Root Cause Analysis of Oncology Adverse Events in the Veterans Health
      Administration.
AB  - PURPOSE: Oncology providers are leaders in patient safety. Despite their efforts,
      oncology-related medical errors still occur, sometimes resulting in patient
      injury or death. The Veterans Health Administration (VHA) National Center of
      Patient Safety used data obtained from root cause analysis (RCA) to determine how
      and why these adverse events occurred in the VHA, and how to prevent future
      reoccurrence. This study details the types of oncology adverse events reported in
      VHA hospitals and their root causes and suggests actions for prevention and
      improvement. METHODS: We searched the National Center for Patient Safety adverse
      event reporting database for RCA related to oncology care from October 1, 2013,
      to September 8, 2017, to identify event types, root causes, severity of outcomes,
      care processes, and suggested actions. Two independent reviewers coded these
      variables, and inter-rater agreement was calculated by kappa statistic. Variables
      were evaluated using descriptive statistics. RESULTS: We identified 48 RCA
      reports that specifically involved an oncology provider. Event types included
      care delays (39.5% [n = 19]), issues with chemotherapy (25% [n = 12]) and
      radiation (12.5% [n = 6]), other (12.5% [n = 6]), and suicide (10.5% [n = 5]). Of
      the 48 events, 27.1% (n = 13) resulted in death, 4.2% (n = 2) in severe harm,
      18.8% (n = 9) in temporary harm, 20.8% (n = 10) in minimal harm, and 2.1% (n = 1)
      in no harm. The majority of root causes identified a need to improve care
      processes and policies, interdisciplinary communication, and care coordination.
      CONCLUSION: This analysis highlights an opportunity to implement system-wide
      changes to prevent similar events from reoccurring. These actions include
      comprehensive cancer clinics, usability testing of medical equipment, and
      standardization of processes and policies. Additional studies are necessary to
      assess oncologic adverse events across specialties.

PMID- 30110228
TI  - Valuing and adequately reporting exploratory research.

PMID- 30110227
TI  - Using Rapid Cycle Improvement (Plan, Do, Study, Act) to Design a Scalable
      Appointment Scheduling System for Complex Oncology Clinical Trials at an Academic
      Cancer Center.
AB  - PURPOSE: This study's purpose was to optimize the efficiency of and to design a
      scalable research scheduling team to meet the growing demands of an academic
      cancer center with increasing clinical trial accruals. METHODS: The Plan, Do,
      Study, Act improvement methodology was deployed to increase the efficiency of
      research scheduling, to reduce non-value-added (NVA) activities, and to reduce
      cycle time to meet takt time. In the Plan phase, voice-of-the-customer interviews
      were conducted. In the Do phase, the baseline workflow was mapped and billing
      data were analyzed. In the Study phase, cycle time, takt time, and capacity
      analysis metrics were calculated at baseline. In the Act phase, interventions
      were implemented to increase efficiency by reducing NVA activities and increasing
      value-added activities, and metrics were reassessed after intervention. RESULTS:
      An 8% increase in appointment requests was noted from baseline to after
      intervention, and the cycle time for appointment scheduling decreased by 11%,
      demonstrating increased efficiency. Process steps decreased from 15 to 10,
      eliminating NVA activities and rework and waiting, two types of waste.
      CONCLUSION: Although efficiency increased, the number of total appointments
      scheduled weekly increased by 4%, resulting in a reduced takt time, or a shorter
      time to schedule each appointment to meet demand. A capacity analysis
      demonstrated that even after interventions, an additional 0.5 full-time employee
      is required to reduce cycle time to equal takt time. Capacity analysis creates a
      scalable framework for the scheduling team and facilitates movement from reactive
      to proactive staffing, which can be applied throughout the research enterprise.

PMID- 30110229
TI  - Nuance in statistical reporting: reply to Heroux.

PMID- 30110230
TI  - Refixation control in free viewing: a specialized mechanism divulged by eye
      movement related brain activity.
AB  - In free viewing, the eyes return to previously visited locations rather
      frequently, even though the attentional and memory-related processes controlling
      eye-movement show a strong anti-refixation bias. To overcome this bias, a special
      refixation triggering mechanism may have to be recruited. We probed the neural
      evidence for such a mechanism by combining eye tracking with EEG recording. A
      distinctive signal associated with refixation planning was observed in the EEG
      during the presaccadic interval: the presaccadic potential was reduced in
      amplitude prior to a refixation, compared to normal fixations. The result offers
      direct evidence for a special refixation mechanism that operates in the saccade
      planning stage of eye-movement control. Once the eyes have landed on the
      revisited location, acquisition of visual information proceeds indistinguishably
      from ordinary fixations.

PMID- 30110232
TI  - Pyramidal cell activity levels affect the polarity of gene transciption changes
      in interneurons.
AB  - Changes in gene expression are an important mechanism by which activity levels
      are regulated in the nervous system. It is not known, however, how network
      activity influences gene expression in interneurons: since they themselves
      provide negative feedback in the form of synaptic inhibition, there exists a
      potential conflict between their cellular homeostatic tendencies, and those of
      the network. We present a means of examining this issue, utilising simple in
      vitro models showing different patterns of intense network activity. We found
      that the degree of concurrent pyramidal activation changed the polarity of the
      induced gene transcription. When pyramidal cells were quiescent, interneuronal
      activation led to an upregulation of Pvalb and GAD1 transcription, mediated by
      activation of the Ras/ERK MAPK pathway. In contrast, co-activation of pyramidal
      cells led to a GluN2B-dependent decrease in transcription. Our results
      demonstrate a hitherto unrecognized complexity in how activity-dependent gene
      expression changes are manifest in cortical networks.

PMID- 30110231
TI  - Optogenetic manipulation of medullary neurons in the locust optic lobe.
AB  - The locust is a widely used animal model for studying sensory processing and its
      relation to behavior. Due to the lack of genomic information, genetic tools to
      manipulate neural circuits in locusts are not yet available. We examined whether
      Semliki Forest virus is suitable to mediate exogenous gene expression in neurons
      of the locust optic lobe. We subcloned a channelrhodopsin variant and the yellow
      fluorescent protein Venus into a Semliki Forest virus vector and injected the
      virus into the optic lobe of locusts ( Schistocerca americana). Fluorescence was
      observed in all injected optic lobes. Most neurons that expressed the recombinant
      proteins were located in the first two neuropils of the optic lobe, the lamina
      and medulla. Extracellular recordings demonstrated that laser illumination
      increased the firing rate of medullary neurons expressing channelrhodopsin. The
      optogenetic activation of the medullary neurons also triggered excitatory
      postsynaptic potentials and firing of a postsynaptic, looming-sensitive neuron,
      the lobula giant movement detector. These results indicate that Semliki Forest
      virus is efficient at mediating transient exogenous gene expression and provides
      a tool to manipulate neural circuits in the locust nervous system and likely
      other insects. NEW & NOTEWORTHY Using Semliki Forest virus, we efficiently
      delivered channelrhodopsin into neurons of the locust optic lobe. We demonstrate
      that laser illumination increases the firing of the medullary neurons expressing
      channelrhodopsin and elicits excitatory postsynaptic potentials and spiking in an
      identified postsynaptic target neuron, the lobula giant movement detector neuron.
      This technique allows the manipulation of neuronal activity in locust neural
      circuits using optogenetics.

PMID- 30110233
TI  - Neuronal population mechanisms of lightness perception.
AB  - The way that humans and animals perceive the lightness of an object depends on
      its physical luminance as well as its surrounding context. While neuronal
      responses throughout the visual pathway are modulated by context, the
      relationship between neuronal responses and lightness perception is poorly
      understood. We searched for a neuronal mechanism of lightness by recording
      responses of neuronal populations in monkey primary visual cortex (V1) and area
      V4 to stimuli that produce a lightness illusion in humans, in which the lightness
      of a disk depends on the context in which it is embedded. We found that the way
      individual units encode the luminance (or equivalently for our stimuli, contrast)
      of the disk and its context is extremely heterogeneous. This motivated us to ask
      whether the population representation in either V1 or V4 satisfies three
      criteria: 1) disk luminance is represented with high fidelity, 2) the context
      surrounding the disk is also represented, and 3) the representations of disk
      luminance and context interact to create a representation of lightness that
      depends on these factors in a manner consistent with human psychophysical
      judgments of disk lightness. We found that populations of units in both V1 and V4
      fulfill the first two criteria, but that we cannot conclude that the two types of
      information in either area interact in a manner that clearly predicts human
      psychophysical measurements: the interpretation of our population measurements
      depends on how subsequent areas read out lightness from the population responses.

PMID- 30110234
TI  - Activity of near response cells during disconjugate saccades in strabismic
      monkeys.
AB  - Infantile strabismus is a common disorder, characterized by a chronic
      misalignment of the eyes, impairment of binocular vision, and oculomotor
      abnormalities. Nonhuman primates with strabismus, induced in infancy, show a
      pattern of abnormalities similar to those of strabismic children. This allows
      strabismic nonhuman primates to serve as an ideal animal model to examine neural
      mechanisms associated with aberrant oculomotor behavior. Here, we test the
      hypothesis that impairment of disparity vergence and horizontal saccade
      disconjugacy in exotropia and esotropia are associated with disrupted tuning of
      near and far response neurons in the supraoculomotor area (SOA). In normal
      animals these neurons carry signals related to vergence position and/or velocity.
      We hypothesized that, in strabismus, these neurons modulate inappropriately in
      association with saccades between equidistant targets. We recorded from 62 SOA
      neurons from 4 strabismic animals (two esotropes and two exotropes) during
      visually guided saccades to a target that stepped to different locations on a
      tangent screen. Under these same conditions SOA neurons in normal animals show no
      detectable modulation. In our strabismic subjects we found that a subset of SOA
      neurons carry weak vergence velocity signals during saccades. In addition, a
      subset of SOA neurons showed clear modulation associated with slow fluctuations
      of horizontal strabismus angle in the absence of a saccade. We suggest that
      abnormal SOA activity contributes to fixation instability but plays only a minor
      role in the horizontal disconjugacy of saccades that do not switch fixation from
      one eye to the other.

PMID- 30110235
TI  - Neurophysiological analysis of the clinical pull test.
AB  - Postural reflexes are impaired in conditions such as Parkinson's disease, leading
      to difficulty walking and falls. In clinical practice, postural responses are
      assessed using the 'pull test', where an examiner tugs the pre-warned, standing
      patient backwards at the shoulders and grades the response. However, validity of
      the pull test is debated with issues including scaling and variability in
      administration and interpretation. It is unclear whether to assess the first
      trial or only subsequent repeated trials. The ecological relevance of a
      forewarned backwards challenge is also debated. We therefore developed an
      instrumented version of the pull test to characterize responses and clarify how
      the test should be performed and interpreted. In thirty-three healthy
      participants, 'pulls' were manually administered and pull force measured. Trunk
      and step responses were assessed with motion tracking. We probed for the
      StartReact phenomenon (where pre-prepared responses are released early by a
      startling stimulus) by delivering concurrent normal or 'startling' auditory
      stimuli. We found that the first pull triggers a different response, including a
      larger step size suggesting more destabilization. This is consistent with 'first
      trial effects', reported by platform translation studies, where movement
      execution appears confounded by startle reflex-like activity. Thus, first pull
      test trials have clinical relevance and should not be discarded as practice.
      Supportive of ecological relevance, responses to repeated pulls exhibited
      StartReact, as previously reported with a variety of other postural challenges
      including those delivered with unexpected timing and direction. Examiner pull
      force significantly affected the postural response particularly the size of
      stepping.

PMID- 30110236
TI  - Rapid homeostatic downregulation of LTP by extrasynaptic GluN2B receptors.
AB  - Although the activation of extrasynaptic GluN2B-containing NMDA receptors have
      been implicated in neurodegenerative diseases such as Alzheimer's and Hungtinton
      Disease, their physiological function remains unknown. In this study, we found
      that extrasynaptic GluN2B receptors play a homeostatic role by antagonizing LTP
      induction under conditions of prolonged synaptic stimulation. In particular, we
      have previously found that brief theta-pulse stimulation (5Hz for 30sec) triggers
      robust LTP whereas longer stimulation times (5Hz for 3min) have no effect on
      basal synaptic transmission in the hippocampal CA1 region. Here, we show that
      prolonged stimulation blocked LTP by activating extrasynaptic GluN2B receptors
      via glutamate spillover. In addition, we found that this homeostatic mechanism
      was absent in slices from the SAP102 knock-out providing evidence for a
      functional coupling between extrasynaptic GluN2B and the SAP102 scaffold protein.
      In conclusion, we uncovered a rapid homeostatic mechanism that antagonizes LTP
      induction via the activation of extrasynaptic GluN2B containing NMDA receptors.

PMID- 30110237
TI  - Inhibition failures and late errors in the antisaccade task: Influence of cue
      delay.
AB  - In the antisaccade task participants are required to saccade in the opposite
      direction of a peripheral visual cue (PVC). This paradigm is often used to
      investigate inhibition of reflexive responses as well as voluntary response
      generation. However, it is not clear to what extent different versions of this
      task probe the same underlying processes. Here, we explored with the Stochastic
      Early Reaction, Inhibition, and late Action (SERIA) model how the delay between
      task cue and PVC affects reaction time (RT) and error rate (ER) when pro- and
      antisaccade trials are randomly interleaved. Specifically, we contrasted a
      condition in which the task cue is presented prior to the PVC with a condition in
      which the PVC serves also as task cue. Summary statistics indicate that ER and
      RTs are reduced and contextual effects largely removed when the task is signaled
      before the PVC appears. The SERIA model accounts for RT and ER in both
      conditions, and better so than other candidate models. Modeling demonstrates that
      voluntary pro- and antisaccades are frequent in both conditions. Moreover, early
      task cue presentation results in better control of reflexive saccades leading to
      fewer fast antisaccade errors and more rapid correct prosaccades. Finally, high
      latency errors are shown to be prevalent in both conditions. In summary, SERIA
      provides an explanation for the differences in the delayed and non-delayed
      antisaccade task.

PMID- 30110238
TI  - Cerebellum and cognition in multiple sclerosis: the fall status matters.
AB  - Kalron et al. report people with Multiple Sclerosis (PwMS) who fall show a
      decreased cerebellar volume along with decreased overall cognition compared to
      non-fallers. While this paper focuses on cerebellar and cognitive alterations in
      PwMS, these findings may also be explained by additional factors such as aging
      and have the potential for broader impact in additional clinical populations who
      simultaneously experience cognitive and mobility dysfunction.

PMID- 30110239
TI  - Exercise-induced muscle damage: What is it, what causes it and what are the
      nutritional solutions?
AB  - Exercise-induced muscle damage (EIMD) is characterized by symptoms that present
      both immediately and for up to 14 days after the initial exercise bout. The main
      consequence of EIMD for the athlete is the loss of skeletal muscle function and
      soreness. As such, numerous nutrients and functional foods have been examined for
      their potential to ameliorate the effects of EIMD and accelerate recovery, which
      is the purpose of many nutritional strategies for the athlete. However, the trade
      off between recovery and adaptation is rarely considered. For example, many
      nutritional interventions described in this review target oxidative stress and
      inflammation, both thought to contribute to EIMD but are also crucial for the
      recovery and adaptation process. This calls into question whether long term
      administration of supplements and functional foods used to target EIMD is indeed
      best practice. This rapidly growing area of sports nutrition will benefit from
      careful consideration of the potential hormetic effect of long term use of
      nutritional aids that ameliorate muscle damage. This review provides a concise
      overview of what EIMD is, its causes and consequences and critically evaluates
      potential nutritional strategies to ameliorate EIMD. We present a pragmatic
      practical summary that can be adopted by practitioners and direct future
      research, with the purpose of pushing the field to better consider the fine
      balance between recovery and adaptation and the potential that nutritional
      interventions have in modulating this balance.

PMID- 30110240
TI  - Homology modeling and structure-based design improve hydrophobic interaction
      chromatography behavior of integrin binding antibodies.
AB  - Monoclonal antibody (mAb) candidates from high-throughput screening or binding
      affinity optimization often contain mutations leading to liabilities for further
      development of the antibody, such as aggregation-prone regions and lack of
      solubility. In this work, we optimized a candidate integrin alpha11-binding mAb
      for developability using molecular modeling, rational design, and hydrophobic
      interaction chromatography (HIC). A homology model of the parental mAb Fv region
      was built, and this revealed hydrophobic patches on the surface of the
      complementarity-determining region loops. A series of 97 variants of the residues
      primarily responsible for the hydrophobic patches were expressed and their HIC
      retention times (RT) were measured. As intended, many of the computationally
      designed variants reduced the HIC RT compared to the parental mAb, and mutating
      residues that contributed most to hydrophobic patches had the greatest effect on
      HIC RT. A retrospective analysis was then performed where 3-dimentional protein
      property descriptors were evaluated for their ability to predict HIC RT using the
      current series of mAbs. The same descriptors were used to train a simple multi
      parameter protein quantitative structure-property relationship model on this
      data, producing an improved correlation. We also extended this analysis to
      recently published HIC data for 137 clinical mAb candidates as well as 31
      adnectin variants, and found that the surface area of hydrophobic patches
      averaged over a molecular dynamics sample consistently correlated to the
      experimental data across a diverse set of biotherapeutics.

PMID- 30110241
TI  - The CMS Proposal to Reform Office-Visit Payments.

PMID- 30110242
TI  - The Next Phase of Human Gene-Therapy Oversight.

PMID- 30110243
TI  - NRC proteins - a critical node for pattern and effector mediated signaling.
AB  - Plants are constantly exposed to numerous diverse microbes and pests. They lack
      an adaptive immune system and rely on innate immunity to perceive and ward off
      potential pathogens. The plant immune system enables plants to overcome invading
      microorganisms, and can be defined as highly successful in this regard.
      Nevertheless, specialized pathogens are able to overcome structural barriers,
      preformed defenses, innate immunity and are a persistent threat to crop and food
      supplies worldwide. The rapidly growing world population results in massive
      demands for agricultural products and reliable crop yields. Therefore, the
      ability to precisely manipulate plant immunity to resist diverse diseases holds
      significant promise for enhancing crop production.

PMID- 30110244
TI  - Examining the influence of grip type on wrist and club head kinematics during the
      golf swing: Benefits of a local co-ordinate system.
AB  - Wrist movements have been identified as an important factor in producing a
      successful golf swing, with their complex motion influencing both club head
      velocity and orientation. However, a detailed analysis of wrist angles is lacking
      in the literature. The purpose of this study was to determine kinematics across
      wrists and club head characteristics during the golf swing under weak, neutral
      and strong grip conditions. Twelve professional male golfers executed 24 shots
      using a driver under three grip conditions. A six degrees of freedom analysis of
      the hand with respect to the distal forearm was performed using a 10-camera three
      dimensional motion capture system. Differences in joint angles were explored
      using repeated measures ANOVAs at key swing events (onset, top of backswing and
      impact), in addition club head velocity and clubface angle at impact were also
      explored. Main findings revealed significant differences in flexion/extension and
      internal/external rotation for both wrists at all swing events, whereas fewer
      significant interactions were found in ulnar/radial deviation across grips for
      both wrists at all events. Clubface angle only differed significantly between the
      weak and the strong and neural grips, presenting a more 'open' clubface to the
      intended hitting direction. This study is the first to explore tri-planar wrist
      movement and the effect of different grips, such analysis has implications for
      coaching knowledge and practice and should inform future research into different
      aspects of skill, technique analysis and may inform injury mechanisms/prevention.

PMID- 30110245
TI  - Downy Mildew: A Serious Disease Threat to Rose Health Worldwide.
AB  - Peronospora sparsa is a downy mildew-causing oomycete that can infect roses,
      blackberries, and other members of the rose family. During the last 70 years,
      this disease has become a serious problem for rose growers in the U.S. and
      worldwide. While much is known about the disease and its treatment, including
      significant research on molecular identification methods, as well as
      environmental conditions conducive to disease and the fungicides used to prevent
      it, significant knowledge gaps remain in our basic comprehension of the
      pathogen's biology. For example, the degree of genetic relatedness of pathogen
      isolates collected from rose, caneberries, and cherry laurel has never been
      examined, and the natural movement of genotypes from host to host is not known.
      Further work could be done to determine the differences in pathogen population
      structure over time (using herbarium specimens and fresh collections) or
      differences in pathogen population structure and pathogen environmental
      adaptation for specimens from different geographic regions. The oospore stage of
      the organism is poorly understood, both as to how it forms and whether it serves
      as an overwintering structure in nurseries and landscapes. In production
      greenhouses, the detection of the pathogen using infrared thermographic imaging
      and possible inhibition by ultraviolet light needs to be explored. Further work
      needs to be done on breeding using wild roses as new sources for resistance and
      using new methods such as marker assisted selection and RNAi technologies. As
      roses are one of the most economically important ornamental crops worldwide, a
      proper understanding of the disease cycle could allow for better use of cultural
      and chemical controls to manage rose downy mildew in landscapes and in greenhouse
      and nursery production areas.

PMID- 30110246
TI  - Characterization and Pathogenicity of Botryosphaeriaceae Fungi Associated with
      Declining Urban Stands of Coast Redwood in California.
AB  - Coast redwood (Sequoia sempervirens) is among the most widely planted landscape
      trees in California (CA) but is in decline outside its natural range due to
      factors including prolonged drought and plant pathogens. We investigated
      associations of Botryosphaeriaceae fungi with declining coast redwood trees
      throughout CA. More than 100 samples were collected from 11 coastal and inland
      locations in CA. Fifty-nine Botryosphaeria-like fungal strains were isolated and
      18 were selected for further study. Phylogenetic analysis of ITS and EF-1alpha
      sequence data confirmed the presence of Botryosphaeria dothidea, Neofusicoccum
      australe, N. luteum, N. mediterraneum, and N. parvum. Pathogenicity testing
      showed that although the Neofusicoccum species vary in virulence, all are more
      virulent that B. dothidea. N. australe caused the largest lesions, followed by N.
      luteum, N. parvum, and N. mediterraneum. Of the species recovered, only B.
      dothidea has been previously confirmed as a pathogen of coast redwood in CA.
      These results confirm that multiple Botryosphaeriaceae species are associated
      with branch decline and dieback on coast redwood in CA, which agrees with similar
      studies on woody agricultural crops. Accurate diagnosis of fungal pathogens of
      coast redwood is important for the development of disease management strategies
      and may help improve horticultural practices in maintenance of urban stands.

PMID- 30110247
TI  - First Report of Capsicum chlorosis orthotospovirus Infecting Zucchini (Cucurbita
      pepo) in China.

PMID- 30110248
TI  - First Report of Anthracnose on Michelia champaca Caused by Colletotrichum
      fioriniae in China.

PMID- 30110249
TI  - A design for external quality assessment for the analysis of thiopurine drugs:
      pitfalls and opportunities.

PMID- 30110250
TI  - High-sensitivity cardiac troponin-I analytical imprecisions evaluated by internal
      quality control or imprecision profile.

PMID- 30110251
TI  - Zataria multiflora extract and carvacrol affect cardiotoxicity induced by
      Adriamycin in rat.

PMID- 30110252
TI  - Antioxidant activity of carob seeds and chemical composition of their bean gum by
      products.

PMID- 30110253
TI  - A lower energetic, protein and uncooked cornstarch intake is associated with a
      more severe outcome in glycogen storage disease type III: an observational study
      of 50 patients.

PMID- 30110254
TI  - Regional differences of hypothermia on oxidative stress following hypoxia
      ischemia: a study of DHA and hypothermia on brain lipid peroxidation in newborn
      piglets.

PMID- 30110255
TI  - Strategies to Enhance the Intravenous Treatment Satisfaction and Drug Safety
      Awareness Among Patients with Multiple Sclerosis in Macedonia.

PMID- 30110256
TI  - Coping Styles Used for Mediation Dental Anxiety and Stress in School Children.

PMID- 30110257
TI  - The Impact of Glyco-Metabolic Status in Patients Treated for Acute Coronary
      Syndrome.

PMID- 30110258
TI  - Growth Hormone Treatment in Children Born Small for Gestational Age (SGA).

PMID- 30110259
TI  - Personality Typology in Patients with Traumatic Limb Fractures.

PMID- 30110260
TI  - Parameters of Metabolic Syndrome in Obese Children and Adolescents.

PMID- 30110261
TI  - Low Molecular Weight Proteinuria in Children with Distal Renal Tubular Acidosis.

PMID- 30110262
TI  - Four Year Results of Conservative Treatment of Benign Strictures of the Esophagus
      with Savary Gilliard Technique of Bougienage: Cross-Sectional Study Representing
      First Experiences in Republic of Macedonia.

PMID- 30110263
TI  - Effects of Short Term Alendronate Administration on Bone Mineral Density in
      Patients with Chronic Kidney Disease.

PMID- 30110264
TI  - Features of Parapneumonic Effusions.

PMID- 30110265
TI  - Epidemiology of Community-Acquired Sepsis in Adult Patients: A Six Year
      Observational Study.

PMID- 30110266
TI  - Lecturers from Macedonia Elected for the First Time to the Faculty of Medicine in
      Skopje in the Period 1961-63.

PMID- 30110267
TI  - Homeostasis Model Assessment - Insulin Resistance and Sensitivity (HOMA-IR and
      IS) Index in Overweight Children Born Small for Gestational Age (SGA).

PMID- 30110268
TI  - Nt-ProBNP Discriminatory Role Between Symptomatic and Asymptomatic Patients with
      Severe Valvular Aortic Stenosis.

PMID- 30110269
TI  - Efficacy of Intraperitoneal Bupivacaine on Pain Relief After Laparoscopic
      Cholecystectomy.

PMID- 30110270
TI  - Clinical Significance of Quantitative HBs Antigen in the Prediction of Liver
      Fibrosis in Patients with Chronic Hepatitis B.

PMID- 30110271
TI  - Analysis of Bone Metabolism in Children with Cystic Fibrosis.

PMID- 30110272
TI  - Originally Adapted Mobile Application Used for Neuropsychiatric Patients.

PMID- 30110273
TI  - Exposure to persistent organic pollutants: impact on women's health.

PMID- 30110275
TI  - Vectorial aberrations of biconic surfaces.
AB  - For non-rotationally symmetric systems, spherical surfaces provide a non
      sufficient effect in correcting aberrations. In anamorphic systems, biconic
      surfaces are used to provide different focal power in tangential and sagittal
      directions. The biconic surface shape is also used as the basic shape of the
      freeform surface representation. The different focal power in tangential and
      sagittal planes generates large field-constant astigmatism, which is decoupled
      from a coma generated by the biconic surface. In this paper, the biconic surface
      sag is expanded up to the fourth order and decomposed into the spherical part,
      the aspherical part, and the freeform part. The vectorial aberrations of the
      biconic surface are derived based on the extended nodal aberration theory. When
      biconic surfaces are used to obtain the initial setup of off-axis systems, it is
      beneficial due to the decoupling of astigmatism and coma. For instance, in the
      initial system design of reflective camera systems, biconic surfaces provide the
      possibility to obtain the nodal point in the center of the field of view, which
      is beneficial for systems with large field of view. This paper provides the
      insight of aberration analysis of biconic surfaces and the conversion of biconic
      surfaces into Zernike fringe freeform surfaces.

PMID- 30110274
TI  - Correlation Between Apolipoprotein M and Inflammatory Factors in Obese Patients.
AB  - BACKGROUND The aim of this study was to observe apolipoprotein M (ApoM) level in
      obese patients and to explore its correlation with inflammatory factors. MATERIAL
      AND METHODS A total number of 96 participants were recruited and divided into 2
      groups: the control group (or healthy group) whose participants had normal body
      weight (n=58), and the obese group with all its participants diagnosed with
      obesity (n=38). Data on blood pressure, body weight, height, body mass index,
      diastolic function of brachial artery endothelium, fasting venous blood glucose,
      blood lipids, plasmatic ApoM, interleukin-6 (IL-6), C-reactive protein (CRP),
      tumor necrosis factor-alpha (TNF-alpha), fasting insulin, and adiponectin levels
      were collected for both groups. RESULTS In the obese group, the levels of
      plasmatic ApoM, high-density lipoprotein cholesterol (HDL-C), and plasmatic
      adiponectin were significantly (p<0.05) decreased compared to the control group,
      and the levels of IL-6, TNF-alpha, CRP, and fasting insulin were significantly
      increased (p<0.05) compared to the control group. For the obese group, plasmatic
      ApoM level was positively correlated with HDL-C level and negatively correlated
      with levels of IL-6, TNF-alpha, CRP, insulin, and insulin resistance index.
      However, no significant correlations were revealed between plasmatic ApoM and the
      diastolic function of brachial artery endothelium, adiponectin level, blood
      pressure, and blood glucose level. CONCLUSIONS Obese patients showed
      significantly lower plasmatic ApoM levels than people with normal body weight,
      and ApoM level showed a strong correlation with CRP, TNF-alpha, and IL-6 levels,
      which indicated that ApoM might be regulated by these inflammatory factors.

PMID- 30110276
TI  - Evolution of near-ground optical turbulence over concrete runway throughout
      multiple days in summer and winter.
AB  - Experimental data are presented that demonstrate the evolution of the
      anisotropy/isotropy of atmospheric statistics throughout the course of four days
      (two winter, two summer) near the ground over a concrete runway in Florida. In
      late January and early February of 2017, a 532 nm near-plane-wave beam was
      propagated 1 and 2 km at a height of 2 m above the runway, and irradiance
      fluctuations were captured on a CCD array. In August of 2017, a 532 nm Gaussian
      beam was propagated 100 m at a height of near 2 m, and fluctuation data were
      captured on a CCD array. Winter data were processed to calculate the covariance
      of intensity and summer data processed to calculate the scintillation index. The
      resulting contours indicated a consistent pattern of anisotropy early in the day,
      evolving into isotropy midday, and returning to anisotropy in late afternoon.
      Accompanying atmospheric and wind data are presented throughout the measurement
      days.

PMID- 30110277
TI  - Scattering matrix of arbitrarily shaped objects: combining finite elements and
      vector partial waves.
AB  - We demonstrate the interest of combining finite element calculations with the
      vector partial wave formulation (used in T-matrix and Mie theory) in order to
      characterize the electromagnetic scattering properties of isolated individual
      scatterers. This method consists of individually feeding the finite element
      problem with incident vector partial waves in order to numerically determine the
      T-matrix elements of the scatterer. For a sphere and a spheroid, we demonstrate
      that this method determines the scattering matrix to high accuracy. Recurrence
      relations for a fast determination of the vector partial waves are given
      explicitly, and an open-source code allowing the retrieval of the presented
      numerical results is provided.

PMID- 30110278
TI  - Solving large-scale general phase retrieval problems via a sequence of convex
      relaxations.
AB  - We present a convex relaxation-based algorithm for large-scale general phase
      retrieval problems. General phase retrieval problems include, e.g., the
      estimation of the phase of the optical field in the pupil plane based on
      intensity measurements of a point source recorded in the image (focal) plane. The
      non-convex problem of finding the complex field that generates the correct
      intensity is reformulated into a rank constraint problem. The nuclear norm is
      used to obtain the convex relaxation of the phase retrieval problem. A new
      iterative method referred to as convex optimization-based phase retrieval (COPR)
      is presented, with each iteration consisting of solving a convex problem. In the
      noise-free case and for a class of phase retrieval problems, the solutions of the
      minimization problems converge linearly or faster towards a correct solution.
      Since the solutions to nuclear norm minimization problems can be computed using
      semidefinite programming, and this tends to be an expensive optimization in terms
      of scalability, we provide a fast algorithm called alternating direction method
      of multipliers (ADMM) that exploits the problem structure. The performance of the
      COPR algorithm is demonstrated in a realistic numerical simulation study,
      demonstrating its improvements in reliability and speed with respect to state-of
      the-art methods.

PMID- 30110279
TI  - Control of plasmon-polariton vortices on the surface of a metal layer.
AB  - Surface plasmon polaritons (SPPs) can be excited at the interface of a metal
      layer and a dielectric layer by various methods. If an inhomogeneity of
      permittivity with a curvilinear boundary is created in the metal layer by the
      external electric field, the incident SPPs and the reflected ones from this
      inhomogeneity interfere with one another. A nonrectangular vortex lattice appears
      when such SPP interference occurs, and the lattice configuration can be
      controlled by varying the external electric field. Based on control of the SPP
      vortex lattice and reading out of the vortex localization, the plasmon logic
      gates "AND," "OR," and "NOT" can be realized. These logic gates represent a
      functionally complete basis for logical operations in processors operating at
      optical frequencies.

PMID- 30110280
TI  - Scintillation and bit error rate analysis of a partially coherent flat-topped
      array laser beam in maritime and terrestrial non-Kolmogorov atmospheric
      environments on a slant path.
AB  - In this paper, on the basis of the extended Huygens-Fresnel principle, a semi
      analytical expression for describing the on-axis scintillation index of a
      partially coherent flat-topped laser beam through non-Kolmogorov maritime and
      terrestrial atmospheric environments on a slant path is derived. Consequently, by
      using the log-normal intensity probability density function, the bit error rate
      (BER) is evaluated. The effects of source factors (such as wavelength, order of
      flatness, and beam width) and the non-Kolmogorov turbulent atmosphere parameters
      (such as the Kolmogorov inner scale, the spectral power-law exponent, and the
      turbulence structure constant) on propagation behavior of the scintillation
      index, and hence on the BER, are studied in detail. Results indicate that an
      increase in the average SNR causes a greater influence of the power-law exponent
      on the BER. Also, it can be deduced that the mean BER increases while the power
      law exponent decreases. In addition, the scintillation index and BER as
      communication link parameters represent the fact that increasing the atmospheric
      refractive-index structure parameter on the ground and decreasing the inner scale
      of turbulence eddies causes an increase in these parameters.

PMID- 30110282
TI  - Optical performance of a dielectric-metal-dielectric antireflective absorber
      structure.
AB  - The absorption of electromagnetic radiation by a planar structure, consisting of
      a three-layer dielectric-metal-dielectric coating on a metal backreflector, is
      analyzed. The conditions for total absorption are derived. Our analysis shows
      that, in contrast with bi-layer structures, the calculated layer thicknesses are
      feasible to fabricate for any metal. The proposed absorber design is of potential
      use in infrared, terahertz, and longer wavelength detectors and for radiant
      energy harvesting devices.

PMID- 30110281
TI  - Three-dimensional single-pixel imaging of incoherent light with spatiotemporally
      modulated illumination.
AB  - We derive analytic expressions for the three-dimensional coherent transfer
      function (CTF) and coherent spread function (CSF) for coherent holographic image
      reconstruction by phase transfer (CHIRPT) microscopy with monochromatic and
      broadband illumination sources. The 3D CSF and CTF were used to simulate CHIRPT
      images, and the results show excellent agreement with experimental data. Finally,
      we show that the formalism presented here for computing the CSF/CTF pair in
      CHIRPT microscopy can be readily extended to other forms of single-pixel imaging,
      such as spatial-frequency-modulated imaging.

PMID- 30110283
TI  - Beam wander of a partially coherent Airy beam in oceanic turbulence.
AB  - The beam wander of a partially coherent Airy beam in oceanic turbulence is
      investigated with the help of the extended Huygens-Fresnel integral formula.
      Analytical expression for the second-order moment and the beam wander of a
      partially coherent Airy beam propagating in oceanic turbulence is derived. From
      the numerical results based on the analytical formula, we find that increasing
      the dissipation rate of turbulent kinetic energy or decreasing the dissipation
      rate of mean-square temperature and relative strength of temperature and salinity
      fluctuations of oceanic turbulence tends to decrease the wander effect of a
      partially coherent Airy beam. Moreover, it is found that increasing the
      transverse scale factor and wavelength or decreasing the coherent length and
      exponential truncation factor of a partially coherent Airy beam decreases beam
      wander in oceanic turbulence. Our results will be useful in optical underwater
      communications and laser defense.

PMID- 30110284
TI  - Linear controller error budget assessment for classical adaptive optics systems.
AB  - Understanding limitations of adaptive optics (AO) systems is crucial when
      designing new systems. In particular, analyzing the potential of different
      controllers is of great interest for the upcoming AO systems of the very large
      telescopes (VLTs) and extremely large telescopes (ELTs). This paper thus details
      a complete error budget assessment formalism, based on analytic formulas
      involving the disturbance temporal power spectral density (PSD) and the
      controller transfer function, and is applicable to any linear controller. This
      formalism is presented here for the special case of classical AO systems, but can
      be extended to any closed- or open-loop, single- or multi-conjugated AO
      configuration. Special attention is paid to the "control-dependent" errors, the
      importance of which is directly related to the type of control used in the AO
      system. The proposed method is applied to a NAOS/VLT-type single conjugated AO
      system, using disturbance PSD derived from a simulated turbulence trajectory or
      estimated from wavefront sensor measurements, enabling the construction of
      detailed error budgets for an integrator and different linear quadratic Gaussian
      controllers. Application to ELT-sized systems is discussed in the conclusion.

PMID- 30110285
TI  - Binocular holographic three-dimensional display using a single spatial light
      modulator and a grating.
AB  - In this paper, a binocular holographic three-dimensional (3D) display system
      combining a single spatial light modulator (SLM) and a grating is proposed and
      implemented. A synthetic phase-only hologram of the left and right 3D perspective
      images of an object is calculated by the layer-based Fresnel diffraction method
      according to the depth information, and uploaded onto the SLM for holographic 3D
      reconstruction with correct depth cues. The grating is designed and fabricated to
      guide the reconstructed left and right 3D perspective images to the corresponding
      eyes. Optical experiments demonstrate that the proposed system can successfully
      present binocular holographic 3D images with both the accommodation effect and
      binocular parallax, which enables observation free of the accommodation-vergence
      conflict and visual fatigue problem.

PMID- 30110286
TI  - Soleillet's formalism of coherence and partial polarization in 2D and 3D:
      application to fluorescence polarimetry.
AB  - We review here the pioneering research conducted by Paul Soleillet on the
      statistical properties of light in his doctoral thesis from 1929 [Ann. Phys.10,
      23 (1929)]. Soleillet's wide-reaching work on polarization, coherence,
      fluorescence scattering, and three-dimensional fields has remained largely
      unrecognized; yet, his original contributions rival the modern rediscoveries in
      both generality and form. Only now, 89 years after Soleillet's original
      publication and stimulated by our current research on fluorescence polarimetry,
      have we been able to fully understand and recognize the significance of his
      results.

PMID- 30110287
TI  - Photon momentum change of quasi-smooth solar sails.
AB  - The solar photon sail (SPS) allows space missions without propellant that would
      otherwise not be feasible. Thrust models frequently used in the literature for
      the calculation of trajectories often underestimate the effect that the surface
      roughness has on SPS dynamics. A small variation of the thrust vector can induce
      a large modification of sail flight. In this work, the variation of the photon
      momentum vector (PMV) is computed as resulting from the incident Sun radiation,
      taking into account the absorbed and reflected photons. The momentum resulting
      from diffuse light has been modeled by using vectorial scattering theories in the
      limit of a quasi-smooth sail where the first-order of Rayleigh-Rice can be
      applied. In particular, the momentum change resulting from diffuse radiation
      causes a PMV reduction as well as a deviation of its direction from what is
      foreseen in the case of an ideally smooth sail.

PMID- 30110288
TI  - Partially coherent microscope in phase space.
AB  - Explicit expressions are presented for different phase-space representations
      (mutual intensity, Wigner distribution function, and ambiguity function) of the
      partially coherent image wave field in a microscope system. These are separated
      into system- and object-dependent parts. The partially coherent image in phase
      space can be described in terms of different 6D system-dependent kernels, all
      Fourier transforms of the system mutual spectrum, the region of overlap of two
      displaced objective pupils and the effective source. The image intensity can be
      expressed in terms of a 4D kernel, the convolution in spatial frequency of the
      source, and the Wigner distribution function of the objective pupil, given by a
      marginal of, or a section through, the respective phase-space kernels.

PMID- 30110289
TI  - Parabolic-Gaussian Schell-model sources and their propagations.
AB  - In this work, a new class of partially coherent Schell-type sources is introduced
      by modifying its degree of coherence, which is a product of a parabolic function
      and a Gaussian function. Such sources are confirmed to be physically genuine and
      may be called parabolic-Gaussian Schell-model (PGSM) sources. The propagating
      expression of the cross-spectral density function of such PGSM sources is derived
      in a general linear optical system. In particular, the propagation properties of
      such PGSM beams in both free space and lens systems are discussed. The results
      show that such PGSM sources can produce dark-hollow intensity profiles in the
      regions of free space very near as well as far away from the source plane, or in
      the focal region of the lens system.

PMID- 30110291
TI  - Propagation and dynamical characteristics of a Bessel-Gaussian beam in a chiral
      medium.
AB  - Based on the ABCD transfer matrix and Collins formula, the analytical expressions
      of the complex amplitude of the Bessel-Gaussian beam in a chiral medium are
      derived. By introducing vector potential in the Lorentz gauge, the
      electromagnetic field components of the Bessel-Gaussian beam are determined under
      the paraxial approximation. Through numerical calculations, the propagation of
      the Bessel-Gaussian beam in a chiral medium is examined. Results show that Bessel
      Gaussian beams split into the left circularly polarized beam and the right
      circularly polarized beam with different propagation trajectories. The
      propagation trajectory of the Bessel-Gaussian beam can be controlled by varying
      half-cone angles of the Bessel-Gaussian beam and the chiral parameter of the
      medium. The dynamical characteristics, including energy, momentum, spin, and
      orbital angular momentum, of Bessel-Gaussian beams in a chiral medium are also
      simulated and discussed in detail. The results will be helpful to understand the
      interaction mechanism between structured light beams and a chiral medium.

PMID- 30110290
TI  - Calculation of light scattering of an elliptical Gaussian beam by a spherical
      particle.
AB  - The use of an elliptical Gaussian beam (EGB) for applications relying on light
      scattering depends much on the ability to evaluate the beam shape coefficients
      (BSC) effectively and accurately. Based on the angular spectrum decomposition
      (ASD) of the radial components of the beam field, we present the formulations of
      the BSCs for the EGB. Numerical calculations of the BSCs, the beam
      reconstruction, and light scattering are performed. The fidelity of the
      reconstructed field to the given one is discussed so as to examine the BSC
      calculation. A comparison of the ASD method with the quadrature and localized
      approximation methods leads to the conclusion that the ASD method is much faster
      than the quadrature method, and it is very powerful for acquiring reliable and
      accurate results of BSCs, even for far off-axis locations and high ellipticities
      of the EGB.

PMID- 30110292
TI  - Symmetries of scattering factors and diffraction efficiencies in grating theory.
AB  - This paper theoretically discusses basic topics on the reciprocity theorem and
      the optical theorem in the grating theory for plane wave reflection and
      transmission from a periodic rough interface between two-layered homogeneous
      media. Based on the shadow theory, symmetries of the scattering factors and
      diffraction efficiencies are newly presented in several formulas.

PMID- 30110293
TI  - Array tilt in the atmosphere and its effect on optical phased array performance.
AB  - This paper investigates atmospheric array tilt and its effect on target-in-the
      loop optical phased array (OPA) performance. Assuming a direct-solve, piston-only
      phase-compensation OPA, two expressions for the atmospheric array tilt variance
      are derived using Mellin transform techniques. The first-the "full" array tilt
      variance-is germane when the OPA is sensitive to atmospheric tilt and is shown to
      significantly impact OPA target-plane intensity. The second-the Zernike-tilt
      removed array tilt variance-is relevant when a separate system compensates for
      atmospheric tilt (the more likely scenario) and is shown to negligibly affect OPA
      performance. To show how atmospheric array tilt errors affect target-plane
      intensity, moments of the far-zone (or focused) array intensity, as functions of
      the array tilt variance, are derived and discussed. Lastly, Monte Carlo
      simulation results are presented to validate the theoretical array tilt variance
      expressions.

PMID- 30110294
TI  - Goos-Hanchen and Imbert-Fedorov shifts of higher-order Laguerre-Gaussian beams
      reflected from a dielectric slab.
AB  - We consider reflection of the Laguerre-Gaussian light beams by a dielectric slab.
      In view of the unified operator approach, the higher-order Laguerre-Gaussian
      beams represent a parametric family with the transverse beam profile given by an
      arbitrary generating parameter. Relying on the Fourier expansion in the focal
      plane of the beam, we compute the Goos-Hanchen and the Imbert-Fedorov shifts for
      light beams with non-zero order and azimuthal index. It is demonstrated that both
      shifts exhibit resonant behavior as functions of the angle of incidence due to
      the interference between the waves reflected from the upper and lower interfaces.
      The centroid shifts strongly depend on the order and azimuthal index of the beam.
      Most interestingly, it is found that the generating parameter of the higher-order
      beam families strongly affects the shifts. Thus, reshaping of the incident
      wavefront with fixed order and azimuthal index changes the linear Goos-Hanchen
      shift up to one half of the beam radius, both negative and positive.

PMID- 30110295
TI  - Fast iterative tomographic wavefront estimation with recursive Toeplitz
      reconstructor structure for large-scale systems.
AB  - Tomographic wavefront reconstruction is the main computational bottleneck to
      realize real-time correction for turbulence-induced wavefront aberrations in
      future laser-assisted tomographic adaptive-optics (AO) systems for ground-based
      giant segmented mirror telescopes because of its unprecedented number of degrees
      of freedom, N, i.e., the number of measurements from wavefront sensors. In this
      paper, we provide an efficient implementation of the minimum-mean-square error
      (MMSE) tomographic wavefront reconstruction, which is mainly useful for some
      classes of AO systems not requiring multi-conjugation, such as laser-tomographic
      AO, multi-object AO, and ground-layer AO systems, but is also applicable to multi
      conjugate AO systems. This work expands that by Conan [Proc. SPIE9148, 91480R
      (2014)PSISDG0277-786X10.1117/12.2054472] to the multi-wavefront tomographic case
      using natural and laser guide stars. The new implementation exploits the Toeplitz
      structure of covariance matrices used in an MMSE reconstructor, which leads to an
      overall O(N log N) real-time complexity compared with O(N2) of the original
      implementation using straight vector-matrix multiplication. We show that the
      Toeplitz-based algorithm leads to 60 nm rms wavefront error improvement for the
      European Extremely Large Telescope laser-tomography AO system over a well-known
      sparse-based tomographic reconstruction; however, the number of iterations
      required for suitable performance is still beyond what a real-time system can
      accommodate to keep up with the time-varying turbulence.

PMID- 30110296
TI  - Segmented fast linear canonical transform.
AB  - Investigation of the discrete and fast linear canonical transforms is becoming
      one of the hottest research topics in modern signal processing and optics. How to
      handle and obtain the linear canonical frequency spectrum of very large input
      data based on equipment with limited memory space is one of the key problems. To
      focus on this problem, a new kind of segmented fast linear canonical transform
      has been proposed in this paper. First, the large data is segmented into short
      data. Thereby, the proposed algorithms can calculate very large input data and
      simultaneously keep the ideal frequency resolution. Second, the complexity of the
      derived algorithms has been analyzed in detail for different kinds of signals.
      Their performance with regard to resolution and precision are compared with the
      existing fast linear canonical transforms. Finally, experimental results are
      presented to verify the correctness of the results obtained.

PMID- 30110297
TI  - Ray-based method for simulating cascaded diffraction in high-numerical-aperture
      systems.
AB  - The electric field at the output of an optical system is in general affected by
      both aberrations and diffraction. Many simulation techniques treat the two
      phenomena separately, using a geometrical propagator to calculate the effects of
      aberrations and a wave-optical propagator to simulate the effects of diffraction.
      We present a ray-based simulation method that accounts for the effects of both
      aberrations and diffraction within a single framework. The method is based on the
      Huygens-Fresnel principle, is entirely performed using Monte Carlo ray tracing,
      and, in contrast to our previously published work, is able to calculate the full
      electromagnetic field. The method can simulate the effects of multiple
      diffraction in systems with a high numerical aperture.

PMID- 30110298
TI  - 3rd-order spherochromatism surface contribution and its intrinsic and induced
      aberration parts.
AB  - An investigation of the chromatic effects in refracting optical systems naturally
      shows that all five Seidel aberrations vary in wavelength because they are all
      dependent on the refractive index. In general, the color variation of spherical
      aberration is denoted as spherochromatism. Besides the chromatic variation of 1st
      order paraxial parameters, e.g., focal length and magnification, described by
      axial and lateral color, spherochromatism can also strongly affect the color
      correction of an optical system. However, to the best of our knowledge, the
      literature shows no exact analytical formula available, specifying this effect.
      Actually, a general 3rd-order description based on the chromatic variation of
      Seidel's surface contribution for spherical aberration has not yet been
      considered. Therefore, this paper deals with this mentioned analytical gap and
      provides a description of a 3rd-order surface contribution for spherochromatism.
      Based on this, the result is analyzed and discussed concerning the
      differentiating between intrinsic and induced aberration parts. In the case of
      spherochromatism, its 3rd-order contribution shows induced effects caused by
      prior summed-up primary color aberrations of the system.

PMID- 30110299
TI  - Young's interference experiment with electromagnetic narrowband light.
AB  - We consider electromagnetic spectral spatial coherence of random stationary light
      beams of arbitrary spectral width. We demonstrate that the normalized spectral
      coherence (or two-point) Stokes parameters and the electromagnetic spectral
      degree of coherence can be measured by narrowband filtering the light and
      detecting the spectral density and the polarization-state fringes around the
      optical axis of Young's interferometer. It is also shown that the normalized
      spectral polarization (or one-point) and coherence Stokes parameters are
      unaffected by filtering, and that the filtered light is strictly cross-spectrally
      pure. We further prove theoretically and confirm experimentally that the (time
      domain) electromagnetic degree of spatial coherence of the filtered light at the
      pinholes does not increase when the passband of the filter is reduced.

PMID- 30110300
TI  - Discrete spherical harmonics method for radiative transfer in scalar planar
      inhomogeneous atmosphere.
AB  - The radiative transfer problems in a participating inhomogeneous scalar planar
      atmosphere, subjected to diffuse or collimated incidence, are investigated using
      the discrete spherical harmonics method. In developing the method, the radiative
      intensity is expanded in a finite series of Legendre polynomials and the
      resulting first-order coupled differential equations of radiance moments are
      expressed in a set of discrete polar directions. The method is applied to
      homogeneous/inhomogeneous atmospheres of various anisotropic scattering degrees
      and thicknesses, and reflective boundary conditions. The discrete spherical
      harmonics method albedo, transmittance, and radiative intensity predictions agree
      well with benchmark literature results. Additionally, numerical predictions show
      that the discrete spherical harmonics method using Mark boundary conditions are
      more efficient than using Marshak boundary conditions.

PMID- 30110301
TI  - Decomposition of a field with smooth wavefront into a set of Gaussian beams with
      non-zero curvatures.
AB  - Decomposition of a general arbitrary field into a set of Gaussian beams has been
      one of the challenges in the Gaussian beam decomposition method for field
      propagation through optical systems. The most commonly used method in this regard
      is the Gabor expansion, which decomposes initial fields into shifted and rotated
      Gaussian beams in a plane. Since the Gaussian beams used have zero initial
      curvatures, the Gabor expansion method does not utilize the ability of the
      Gaussian beams to represent the quadratic behavior of the local wavefront. In
      this paper, we describe an alternative method of decomposing an arbitrary field
      with smooth wavefront into a set of Gaussian beams with non-zero initial
      curvatures. The individual Gaussian beams are used to represent up to the
      quadratic term in the Taylor expansion of the local wavefront. This significantly
      reduces the number of Gaussian beams required for the decomposition of the field
      with smooth wavefront and gives more accurate decomposition results. The proposed
      method directly gives the five ray sets representing the parabasal Gaussian
      beams, which can then be directly used for propagation of the Gaussian beams
      through optical systems. To demonstrate the application of the method, we have
      presented results for the decomposition of fields with strongly curved spherical
      wavefronts, a cone shaped wavefront, and a wavefront with large spherical
      aberration. The numerical comparison of the input field with the field
      reconstructed after the decomposition shows very good agreement in both amplitude
      and phase profiles. We also show results for the far field intensity
      distributions of the decomposed wavefronts by propagating in free space using the
      Gaussian beam propagation method.

PMID- 30110302
TI  - Full-wave optimization of three-dimensional photonic-crystal structures involving
      dielectric rods.
AB  - We present rigorous optimization and design of three-dimensional photonic-crystal
      (PhC) structures involving finite dielectric rods. These types of PhCs are known
      to be useful in diverse applications, such as imaging, power focusing, filtering,
      and pattern shaping at optical frequencies. Without resorting to their two
      dimensional models, which are commonly used in the literature, we consider PhCs
      as three-dimensional structures, whose electromagnetic characteristics are
      optimized via genetic algorithms integrated with an efficient and accurate solver
      based on the multilevel fast multipole algorithm. In addition to the designs of
      PhCs that can provide desired output patterns, we present sensitivity tests to
      understand the critical geometric parameters, as well as to test and evaluate the
      tolerance of the proposed designs to possible fabrication errors.

PMID- 30110303
TI  - Geometrical ray tracing in uniaxial crystals: direct formulas and the equivalence
      between the electromagnetic wave method and Huygens' principle.
AB  - Using the electromagnetic wave method and Huygens' principle, we have studied
      light refraction and reflection on the boundary between two uniaxial crystals
      with arbitrary optic axis orientations. We provide a set of direct formulas that
      calculate the directions of the refracted and reflected extraordinary rays and
      their associated waves, as well as the ray indices and refractive indices. The
      formulas use only the initial input variables and do not require the calculation
      of intermediate quantities. Refraction and reflection are combined in one
      formula. We also prove that the electromagnetic wave method and Huygens'
      principle produce analytically equivalent results for geometrical ray tracing.

PMID- 30110304
TI  - Quantifying the effect of straylight on photopic contrast sensitivity.
AB  - The visual performance of a reference group (RG) using diffuser filters was
      compared to a cataract-diagnosed group (CatG). Measurements of straylight (SL)
      parameter, photopic contrast sensitivity (CS), and visual acuity (VA) were
      carried out in both groups. Before the analysis, the performance of the
      instruments used for this purpose was tested. The RG was comprised of three
      healthy, young eyes (25-30 years old) while 59 subjects (aged 50-80 years old)
      with lens opacities were recruited for the CatG. Six diffuser conditions were
      tested in the RG. To discriminate between light scattering levels, SL
      measurements proved to be most sensitive, VA did not discriminate at all, while
      CS showed intermediate sensitivity. VA was not correlated with SL, while the
      correlation between CS and SL was significant (p<0.05) in both groups. Since the
      correlation in the RG was particularly strong, parameters of a linear regression
      model are presented. The behavior of CS as a function of SL was comparable to
      some extent between RG and CatG.

PMID- 30110305
TI  - Experimental and theoretical investigation of the co-occurrence of linear and
      circular dichroisms for oblique incidence of light on chiral sculptured thin
      films.
AB  - Theory shows that a slab of a dielectric structurally chiral material (DSCM)
      exhibits both linear and circular dichroisms because of its anisotropy and
      structural chirality, for normal as well as oblique incidence. This conclusion
      was confirmed by fabricating a chiral sculptured thin film and measuring the
      spectra of its reflectances and transmittances, both linear and circular.
      Signatures of the circular Bragg phenomenon are evident in the spectra of all
      reflectances, transmittances, absorptances, and dichroisms. Reversal of the
      structural handedness of a DSCM and rotation of the projection of the direction
      of propagation of the incident light clockwise instead of counterclockwise about
      the axis of helicoidal nonhomogeneity simultaneously changes the sign of circular
      dichroism but has no effect on linear dichroism.

PMID- 30110306
TI  - Jacobi circle and annular polynomials: modal wavefront reconstruction from
      wavefront gradient.
AB  - Jacobi circle polynomials, which are orthogonal on the unit circle with
      orthogonal radial derivatives, have been developed previously. As the classical
      Zernike mode can be represented as a linear combination of Jacobi modes, Zernike
      wavefront modes can be reconstructed using Jacobi modes. Comparison of the Jacobi
      and Zernike modes for the modal approach indicates that a modal approach
      incorporating the Gram matrix with the Jacobi modes has potential application in
      high-sampling wavefront gradient sensors. The Gram matrix method using the Jacobi
      modes can be extended to annular pupils.

PMID- 30110307
TI  - Pixel-level alignment of facial images for high accuracy recognition using
      ensemble of patches.
AB  - The variation of pose, illumination, and expression continues to make face
      recognition a challenging problem. As a pre-processing step in holistic
      approaches, faces are usually aligned by eyes. The proposed method tries to
      perform a pixel alignment rather than eye alignment by mapping the geometry of
      faces to a reference face while keeping their own textures. The proposed geometry
      alignment not only creates a meaningful correspondence among every pixel of all
      faces, but also removes expression and pose variations effectively. The geometry
      alignment is performed pixel-wise, i.e., every pixel of the face is corresponded
      to a pixel of the reference face. In the proposed method, the information of
      intensity and geometry of faces is separated properly, trained by separate
      classifiers, and finally fused together to recognize human faces. Experimental
      results show a great improvement using the proposed method in comparison to eye
      aligned recognition. For instance, at the false acceptance rate (FAR) of 0.001,
      the recognition rates are respectively improved by 24% and 33% in the Yale and
      AT&T datasets. In the labeled faces in the wild dataset, which is a challenging,
      big dataset, improvement is 20% at a FAR of 0.1.

PMID- 30110308
TI  - Experimental demonstration of ray-rotation sheets.
AB  - We have built microstructured sheets that rotate, on transmission, the direction
      of light rays by an arbitrary, but fixed, angle around the sheet normal. These
      ray-rotation sheets comprise two pairs of confocal lenticular arrays. In addition
      to rotating the direction of transmitted light rays, our sheets also offset ray
      position sideways on the scale of the diameter of the lenticules. If this ray
      offset is sufficiently small so that it cannot be resolved, our ray-rotation
      sheets appear to perform generalized refraction.

PMID- 30110309
TI  - Propagation of annular cos-Gaussian beams through turbulence.
AB  - The propagation characteristics of annular cos-Gaussian beams and Bessel-Gaussian
      beams in turbulence have been widely investigated. However, the expression of the
      average intensity of Bessel-Gaussian beams involves a complex double integral,
      which requires large computational resources and does not easily ensure accuracy.
      Under this background, through the general cos-Gaussian beam rotation, a new
      annular cos-Gaussian beam is proposed which not only has some properties of the
      general cos-Gaussian beam, but also properties similar to those of the Bessel
      Gaussian beam. Moreover, the annular cos-Gaussian beam is simpler in form than
      the general one and much more time-saving in calculation than the Bessel-Gaussian
      beams. Based on the extended Huygens-Fresnel principle, the average intensity on
      a receiver plane of the annular cos-Gaussian beams can be simplified to a
      summation of several polynomials and it is in good agreement with that of low
      order Bessel Gaussian beams. The average radius and the power in the bucket are
      also derived. In summary, the annular cos-Gaussian beam has promising
      applications for its quick calculation and simple form among annular beams and
      hollow beams.

PMID- 30110310
TI  - Second-order moments of a twisted Gaussian Schell-model beam in anisotropic
      turbulence.
AB  - Analytical formulas for the Wigner distribution functions and the second-order
      moments (SOMs) of a twisted Gaussian Schell-model (TGSM) beam propagating through
      anisotropic turbulence have been derived by means of a tensor method. It is found
      that the propagation law for the SOMs of a TGSM beam spreading in turbulence can
      be described as a first-order optical systems propagation law with an additional
      turbulence-induced effect. Based on the SOMs, second-order statistics in terms of
      the effective beam width, the M2-factor, the orbital angular momentum flux, and
      the effective radius curvature are analyzed in detail. One finds that the
      anisotropic turbulence leads to an anisotropic spreading of light beams, and a
      TGSM beam is less affected by turbulence than a Gaussian Schell-model beam
      without the twist phase. For short distance propagation, the light beam is more
      sensitive to the initial beam parameters than turbulence parameters, while for
      sufficiently long transmission distance, the beam characteristics are determined
      at most by turbulence statistics. The method can be extended to study the
      propagation characteristics of various coherent and partially coherent complex
      Gaussian beams, such as flat-topped beams, dark hollow beams, and array beams in
      turbulence, and promotes important supports in free-space optical communications
      and remote sensing.

PMID- 30110311
TI  - Binocular system with asymmetric eyes.
AB  - I elaborate binocular geometry with a novel eye model that incorporates the
      fovea's temporalward displacement and the cornea and the lens' misalignment. The
      formulated binocular correspondence results in longitudinal horopters that are
      conic sections resembling empirical horopters. When the eye model's asymmetry
      parameters' range is that which is observed in healthy eyes, abathic distance
      also falls within its experimentally observed range. This range in abathic
      distance is similar to that of the vergence resting position distance. Further,
      the conic's orientation is specified by the eyes' version angle, integrating
      binocular geometry with eye movement. This integration presents the possibility
      for modeling 3D perceptual stability during physiological eye movements.

PMID- 30110312
TI  - Halo and subsurface scattering in the transparent coating on top of a diffusing
      material.
AB  - Strongly scattering supports coated with thick transparent medium display a
      bright halo with a characteristic ring shape when illuminated in one point by a
      thin pencil of light. The halo, whose size is related to the coating thickness,
      is due to the Fresnel internal reflections of the light scattered by the
      diffusing support at the coating-air interface. The angular distribution of the
      reflected light strongly varies over the halo according to the distance from the
      point initially illuminated, a fact that cannot be observed when a large area of
      the surface is illuminated as in usual reflectance and bidirectional reflectance
      distribution function measurements. By considering a Lambertian background and a
      transparent layer on top of it, both of them being possibly absorbing, we develop
      a bidirectional subsurface scattering reflectance distribution function model,
      based on analytical equations and matrix numerical computation, which enables a
      detailed description of the spatial and angular distribution of the scattered
      light including the multiple reflections between the background and the coating
      air interface. Some applications in which this subsurface scattering phenomenon
      can be an issue are addressed, such as the reflectance measurement, which can be
      undervalued when the geometry is not adapted to the coating thickness, or the
      impact of the phenomenon on heterogeneously colored surfaces such as coated or
      laminated halftone prints.

PMID- 30110313
TI  - Polarization coherent optical communications with adaptive polarization control
      over atmospheric turbulence.
AB  - In wireless optical communication systems, the coherent detection scheme suffers
      severe performance degradation due to the phase fluctuation and polarization
      offset. To deal with such challenges, we propose a polarization coherent optical
      communication scheme with adaptive polarization control (PCPC), where the
      transmitted continuous-wave light is split into two paths-the binary phase shift
      keying modulated signal light and the reference light-which are orthogonally
      polarized and combined before being sent to free space. In the receiving site,
      the interference between the two lights can effectively suppress the atmospheric
      turbulence-induced phase fluctuation. Furthermore, we propose an adaptive
      polarization control scheme for eliminating the polarization offset caused by the
      transceiver misalignment and the atmospheric turbulence. Performance evaluation
      of the PCPC scheme with analytical expressions and numerical simulations shows
      that the PCPC scheme can effectively suppress the phase fluctuation without phase
      locked loop and phase tracking algorithm; thus, the PCPC scheme outperforms the
      traditional coherent modulation in the turbulence channel. An elaborate designed
      indoor experiment was implemented to verify the scheme performance, where the
      measured residual phase fluctuation and measured residual polarization offset are
      both very small, and the experimental bit error rate performance can conform
      closely to the theory.

PMID- 30110314
TI  - Wavelet-based iterative perfect reconstruction in computational integral imaging.
AB  - We propose a new computational integral imaging (CII) method via the iterative
      perfect reconstruction technique to improve the visual quality of reconstructed
      3D scenes. As is well known, images reconstructed by CII suffer from artifacts
      and, as a result, degradation of visual quality. As solutions to this problem,
      the regularization and iterative back-projection (IBP)-based super-resolution
      (SR) reconstruction algorithms have been shown to be effective for high-visual
      quality reconstruction. However, computation of the regularization algorithm is
      very expensive, and the IBP algorithm is very sensitive to noise in the
      deblurring process. To address these challenges, we propose an iterative perfect
      reconstruction algorithm that addresses the issues of low visual quality and
      noise sensitivity. Experimental results indicate that our proposed method
      outperforms the conventional SR reconstruction-based CII methods.

PMID- 30110315
TI  - Probing spin density at the nanoscale using spin-orbital coupling in light
      scattering.
AB  - We propose a scattering-type nano-polarimeter for probing the local spin density
      with subwavelength spatial resolution via the spin-orbital interactions at the
      nanoscale. The nano-polarimeter is simple to operate and can be applied to a
      variety of asymmetric nanoprobes, allowing direct data retrieval using two point
      detectors. Moreover, this technique is not limited to the spin-density detection
      but can also be used for the measurement of any given polarization states of
      light, no matter whether it is a free-space propagating wave or nonpropagating
      wave bound in the near-field region of nanostructures.

PMID- 30110316
TI  - Expectation-maximization algorithm for amplitude estimation of saturated optical
      transient signals.
AB  - This paper addresses parameter estimation for an optical transient signal when
      the received data has been right-censored. We develop an expectation-maximization
      (EM) algorithm to estimate the amplitude of a Poisson intensity with a known
      shape in the presence of additive background counts, where the measurements are
      subject to saturation effects. We compare the results of our algorithm with those
      of an EM algorithm that is unaware of the censoring.

PMID- 30110317
TI  - Modal-based phase retrieval using Gaussian radial basis functions.
AB  - In this paper, we propose the use of Gaussian radial basis functions (GRBFs) to
      model the generalized pupil function for phase retrieval. The selection of the
      GRBF hyper-parameters is analyzed to achieve an increased accuracy of
      approximation. The performance of the GRBF-based method is compared in a
      simulation study with another modal-based approach considering extended Nijboer
      Zernike (ENZ) polynomials. The almost local character of the GRBFs makes them a
      much more flexible basis with respect to the pupil geometry. It has been shown
      that for aberrations containing higher spatial frequencies, the GRBFs outperform
      ENZ polynomials significantly, even on a circular pupil. Moreover, the
      flexibility has been demonstrated by considering the phase retrieval problem on
      an annular pupil.

PMID- 30110318
TI  - Petal-like zone plate: long depth bifocal diffractive lens and star-like beam
      generator.
AB  - This study introduces and examines the diffraction properties of a so-called
      petal-like zone plate, which comprises Fresnel zones analogous to petals. We show
      that the focusing behavior of this novel type of zone plate depends on the number
      of petals included in the element. For a small value of the petal frequency, we
      observe star-like diffraction patterns at the focal plane, whose number of star
      arms equals the petal frequency of the element when the frequency is an odd
      integer and is twice as large as the petal frequency when it is an even number.
      In addition, we have shown that the star-like pattern rotates when it passes
      through the focus. Moreover, it is demonstrated that the element acts as a long
      depth bifocal diffractive lens for a large value of the petal frequency. The
      spacing between the foci is simply controlled by a so-called shifting parameter.
      At the same time, an annular beam is observed in the middle of the line joining
      the two foci together. Consequently, an axial bottle-like beam is produced around
      the focus, whose size could be simply monitored. Simulation results are followed
      and verified by experimental works.

PMID- 30110319
TI  - Compositionality in animals and humans.
AB  - A key step in understanding the evolution of human language involves unravelling
      the origins of language's syntactic structure. One approach seeks to reduce the
      core of syntax in humans to a single principle of recursive combination, merge,
      for which there is no evidence in other species. We argue for an alternative
      approach. We review evidence that beneath the staggering complexity of human
      syntax, there is an extensive layer of nonproductive, nonhierarchical syntax that
      can be fruitfully compared to animal call combinations. This is the essential
      groundwork that must be explored and integrated before we can elucidate, with
      sufficient precision, what exactly made it possible for human language to explode
      its syntactic capacity, transitioning from simple nonproductive combinations to
      the unrivalled complexity that we now have.

PMID- 30110321
TI  - Call combinations in birds and the evolution of compositional syntax.
AB  - Syntax is the set of rules for combining words into phrases, providing the basis
      for the generative power of linguistic expressions. In human language, the
      principle of compositionality governs how words are combined into a larger unit,
      the meaning of which depends on both the meanings of the words and the way in
      which they are combined. This linguistic capability, i.e., compositional syntax,
      has long been considered a trait unique to human language. Here, we review recent
      studies on call combinations in a passerine bird, the Japanese tit (Parus minor),
      that provide the first firm evidence for compositional syntax in a nonhuman
      animal. While it has been suggested that the findings of these studies fail to
      provide evidence for compositionality in Japanese tits, this criticism is based
      on misunderstanding of experimental design, misrepresentation of the importance
      of word order in human syntax, and necessitating linguistic capabilities beyond
      those given by the standard definition of compositionality. We argue that
      research on avian call combinations has provided the first steps in elucidating
      how compositional expressions could have emerged in animal communication systems.

PMID- 30110320
TI  - Serial representation of items during working memory maintenance at letter
      selective cortical sites.
AB  - A key component of working memory is the ability to remember multiple items
      simultaneously. To understand how the human brain maintains multiple items in
      memory, we examined direct brain recordings of neural oscillations from
      neurosurgical patients as they performed a working memory task. We analyzed the
      data to identify the neural representations of individual memory items by
      identifying recording sites with broadband gamma activity that varied according
      to the identity of the letter a subject viewed. Next, we tested a previously
      proposed model of working memory, which had hypothesized that the neural
      representations of individual memory items sequentially occurred at different
      phases of the theta/alpha cycle. Consistent with this model, the phase of the
      theta/alpha oscillation when stimulus-related gamma activity occurred during
      maintenance reflected the order of list presentation. These results suggest that
      working memory is organized by a cortical phase code coordinated by coupled
      theta/alpha and gamma oscillations and, more broadly, provide support for the
      serial representation of items in working memory.

PMID- 30110324
TI  - Physicochemical characteristics and high sensory acceptability in cappuccinos
      made with jackfruit seeds replacing cocoa powder.
AB  - Jackfruit seeds are an under-utilized waste product in many tropical countries.
      In this work, we demonstrate the potential of roasted jackfruit seeds to
      substitute for cocoa powder in cappuccino formulations. Two different flours were
      produced from a hard variety jackfruit by drying or fermenting the seeds prior to
      roasting. Next, formulations were prepared with 50%, 75%, and 100% substitution
      of cocoa powder with jackfruit seed flours, totalizing seven with control
      formulation. The acceptance of cappuccinos by consumers (n = 126) and
      quantitative descriptive analysis (QDA(r)) were used to describe the
      preparations. Physicochemical properties were also evaluated. When 50% and 75%
      cocoa powder was replaced with dry jackfruit seed flour, there was no change in
      sensory acceptability or technological properties; however, it is possible to
      identify advantages tousing dry jackfruit seed flour, including moisture
      reduction and high wettability, solubility and sensory acceptation of the
      chocolate aroma. The principal component analysis of QDA explained90% variances;
      cluster analysis enabled the definition of four groups for six cappuccino
      preparations. In fact, dry jackfruit seed flour is an innovative cocoa powder
      substitute; it could be used in food preparations, consequently utilizing this
      tropical fruit waste by incorporating it as an ingredient in a common product of
      the human diet.

PMID- 30110322
TI  - Accounting for non-stationarity in epidemiology by embedding time-varying
      parameters in stochastic models.
AB  - The spread of disease through human populations is complex. The characteristics
      of disease propagation evolve with time, as a result of a multitude of
      environmental and anthropic factors, this non-stationarity is a key factor in
      this huge complexity. In the absence of appropriate external data sources, to
      correctly describe the disease propagation, we explore a flexible approach, based
      on stochastic models for the disease dynamics, and on diffusion processes for the
      parameter dynamics. Using such a diffusion process has the advantage of not
      requiring a specific mathematical function for the parameter dynamics. Coupled
      with particle MCMC, this approach allows us to reconstruct the time evolution of
      some key parameters (average transmission rate for instance). Thus, by capturing
      the time-varying nature of the different mechanisms involved in disease
      propagation, the epidemic can be described. Firstly we demonstrate the efficiency
      of this methodology on a toy model, where the parameters and the observation
      process are known. Applied then to real datasets, our methodology is able, based
      solely on simple stochastic models, to reconstruct complex epidemics, such as flu
      or dengue, over long time periods. Hence we demonstrate that time-varying
      parameters can improve the accuracy of model performances, and we suggest that
      our methodology can be used as a first step towards a better understanding of a
      complex epidemic, in situation where data is limited and/or uncertain.

PMID- 30110323
TI  - FMRFa receptor stimulated Ca2+ signals alter the activity of flight modulating
      central dopaminergic neurons in Drosophila melanogaster.
AB  - Neuropeptide signaling influences animal behavior by modulating neuronal activity
      and thus altering circuit dynamics. Insect flight is a key innate behavior that
      very likely requires robust neuromodulation. Cellular and molecular components
      that help modulate flight behavior are therefore of interest and require
      investigation. In a genetic RNAi screen for G-protein coupled receptors that
      regulate flight bout durations, we earlier identified several receptors,
      including the receptor for the neuropeptide FMRFa (FMRFaR). To further
      investigate modulation of insect flight by FMRFa we generated CRISPR-Cas9 mutants
      in the gene encoding the Drosophila FMRFaR. The mutants exhibit significant
      flight deficits with a focus in dopaminergic cells. Expression of a receptor
      specific RNAi in adult central dopaminergic neurons resulted in progressive loss
      of sustained flight. Further, genetic and cellular assays demonstrated that
      FMRFaR stimulates intracellular calcium signaling through the IP3R and helps
      maintain neuronal excitability in a subset of dopaminergic neurons for positive
      modulation of flight bout durations.

PMID- 30110325
TI  - Correction: Deletion of Nkx2-5 in trabecular myocardium reveals the developmental
      origins of pathological heterogeneity associated with ventricular non-compaction
      cardiomyopathy.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1007502.].

PMID- 30110326
TI  - The identification of cases of major hemorrhage during hospitalization in
      patients with acute leukemia using routinely recorded healthcare data.
AB  - INTRODUCTION: Electronic health care data offers the opportunity to study rare
      events, although detecting these events in large datasets remains difficult. We
      aimed to develop a model to identify leukemia patients with major hemorrhages
      within routinely recorded health records. METHODS: The model was developed using
      routinely recorded health records of a cohort of leukemia patients admitted to an
      academic hospital in the Netherlands between June 2011 and December 2015. Major
      hemorrhage was assessed by chart review. The model comprised CT-brain, hemoglobin
      drop, and transfusion need within 24 hours for which the best discriminating cut
      off values were taken. External validation was performed within a cohort of two
      other academic hospitals. RESULTS: The derivation cohort consisted of 255
      patients, 10,638 hospitalization days, of which chart review was performed for
      353 days. The incidence of major hemorrhage was 0.22 per 100 days in hospital.
      The model consisted of CT-brain (yes/no), hemoglobin drop of >=0.8 g/dl and
      transfusion of >=6 units. The C-statistic was 0.988 (CI 0.981-0.995). In the
      external validation cohort of 436 patients (19,188 days), the incidence of major
      hemorrhage was 0.46 per 100 hospitalization days and the C-statistic was 0.975
      (CI 0.970-0.980). Presence of at least one indicator had a sensitivity of 100%
      (CI 95.8-100) and a specificity of 90.7% (CI 90.2-91.1). The number of days to
      screen to find one case decreased from 217.4 to 23.6. INTERPRETATION: A model
      based on information on CT-brain, hemoglobin drop and need of transfusions can
      accurately identify cases of major hemorrhage within routinely recorded health
      records.

PMID- 30110327
TI  - The roles of SMYD4 in epigenetic regulation of cardiac development in zebrafish.
AB  - SMYD4 belongs to a family of lysine methyltransferases. We analyzed the role of
      smyd4 in zebrafish development by generating a smyd4 mutant zebrafish line
      (smyd4L544Efs*1) using the CRISPR/Cas9 technology. The maternal and zygotic
      smyd4L544Efs*1 mutants demonstrated severe cardiac malformations, including
      defects in left-right patterning and looping and hypoplastic ventricles,
      suggesting that smyd4 was critical for heart development. Importantly, we
      identified two rare SMYD4 genetic variants in a 208-patient cohort with
      congenital heart defects. Both biochemical and functional analyses indicated that
      SMYD4(G345D) was pathogenic. Our data suggested that smyd4 functions as a histone
      methyltransferase and, by interacting with HDAC1, also serves as a potential
      modulator for histone acetylation. Transcriptome and bioinformatics analyses of
      smyd4L544Efs*1 and wild-type developing hearts suggested that smyd4 is a key
      epigenetic regulator involved in regulating endoplasmic reticulum-mediated
      protein processing and several important metabolic pathways in developing
      zebrafish hearts.

PMID- 30110329
TI  - The effect of temperature increase on the development of Rhodnius prolixus and
      the course of Trypanosoma cruzi metacyclogenesis.
AB  - The increase in the global land temperature, expected under predictions of
      climate change, can directly affect the transmission of some infectious diseases,
      including Chagas disease, an anthropozoonosis caused by Trypanosoma cruzi and
      transmitted by arthropod vectors of the subfamily Triatominae. This work seeks to
      study the effects of temperature on the development of the life cycle, fertility
      and fecundity of the insect vector Rhodnius prolixus and on the metacyclogenesis
      of T. cruzi. All of the variables were subjected to 3 temperatures: 26 degrees C,
      28 degrees C and 30 degrees C. Hatching time was evaluated, along with time to
      fifth instar, time to adult, fecundity studied using the e-value, and egg
      viability during the first 3 reproductive cycles. In addition, the amounts of
      metacyclic trypomastigotes of the TcI and TcII DTUs in R. prolixus were evaluated
      from days 2 to 20 at two-day intervals and from weeks 6 to 8 post-infection.
      Decreases were observed in time to hatching (15-10 days on average) and in time
      to fifth instar (70-60 days on average) and transition to adult (100-85 days on
      average). No significant differences in egg viability were observed in any of the
      reproductive cycles evaluated, but an increase in fecundity was observed at 30
      degrees C during the third reproductive cycle. At 30 degrees C, there was also an
      increase in the number of infective forms and a decrease in the time at which
      metacyclic trypomastigotes were detected in the rectal ampulla of the insects for
      both TcI and TcII. According to these results, the expected temperature increase
      under climate change would cause an increase in the number of insects and a
      greater probability of infection of the parasite, which affects the transmission
      of Chagas disease.

PMID- 30110330
TI  - Comparing teacher and student perspectives on the interplay of cognitive and
      motivational-affective student characteristics.
AB  - For students, cognitive and motivational-affective characteristics are the most
      powerful prerequisites for successful learning. For teachers, judgments on their
      students' characteristics shape how they plan and implement instructional
      activities in order to offer individual learning support. On the student side,
      research is starting to find out more about the interplay of different
      characteristics within individual students. On the teacher side, studies still
      regard teacher judgment accuracy of only single characteristics. By taking a
      person-centered approach, regarding NS = 503 students and their NT = 41
      mathematics and languages arts teachers, our manuscript joined teacher and
      student perspectives on student characteristics interplay and suggests
      methodology to compare them. We found that student assessments suggested ample
      diversity regarding this interplay-and teachers did not perceive this. In their
      views, "homogeneous" sets of average characteristics were dominant. Findings
      suggest addressing students' views and the diagnosis of their characteristics in
      teacher education to enable individual support.

PMID- 30110328
TI  - The bithorax complex iab-7 Polycomb response element has a novel role in the
      functioning of the Fab-7 chromatin boundary.
AB  - Expression of the three bithorax complex homeotic genes is orchestrated by nine
      parasegment-specific regulatory domains. Autonomy of each domain is conferred by
      boundary elements (insulators). Here, we have used an in situ replacement
      strategy to reanalyze the sequences required for the functioning of one of the
      best-characterized fly boundaries, Fab-7. It was initially identified by a
      deletion, Fab-71, that transformed parasegment (PS) 11 into a duplicate copy of
      PS12. Fab-71 deleted four nuclease hypersensitive sites, HS*, HS1, HS2, and HS3,
      located between the iab-6 and iab-7 regulatory domains. Transgenic and P-element
      excision experiments mapped the boundary to HS*+HS1+HS2, while HS3 was shown to
      be the iab-7 Polycomb response element (PRE). Recent replacement experiments
      showed that HS1 is both necessary and sufficient for boundary activity when HS3
      is also present in the replacement construct. Surprisingly, while HS1+HS3
      combination has full boundary activity, we discovered that HS1 alone has only
      minimal function. Moreover, when combined with HS3, only the distal half of HS1,
      dHS1, is needed. A ~1,000 kD multiprotein complex containing the GAF protein,
      called the LBC, binds to the dHS1 sequence and we show that mutations in dHS1,
      that disrupt LBC binding in nuclear extracts, eliminate boundary activity and GAF
      binding in vivo. HS3 has binding sites for GAF and Pho proteins that are required
      for PRE silencing. In contrast, HS3 boundary activity only requires the GAF
      binding sites. LBC binding with HS3 in nuclear extracts, and GAF association in
      vivo, depend upon the HS3 GAF sites, but not the Pho sites. Consistent with a
      role for the LBC in HS3 boundary activity, the boundary function of the
      dHS1+HS3mPho combination is lost when the flies are heterozygous for a mutation
      in the GAF gene. Taken together, these results reveal a novel function for the
      iab-7 PREs in chromosome architecture.

PMID- 30110331
TI  - Evaluating the costs and benefits of marsh-management strategies while accounting
      for uncertain sea-level rise and ecosystem response.
AB  - Prioritization of marsh-management strategies is a difficult task as it requires
      a manager to evaluate the relative benefits of each strategy given uncertainty in
      future sea-level rise and in dynamic marsh response. A modeling framework to
      evaluate the costs and benefits of management strategies while accounting for
      both of these uncertainties has been developed. The base data for the tool are
      high-resolution uncertainty-analysis results from the SLAMM (Sea-Level Affecting
      Marshes Model) under different adaptive-management strategies. These results are
      combined with an ecosystem-valuation assessment from stakeholders. The SLAMM
      results and stakeholder values are linked together using "utility functions" that
      characterize the relationship between stakeholder values and geometric metrics
      such as "marsh area," marsh edge," or "marsh width." The expected-value of each
      site's ecosystem benefits can then be calculated and compared using estimated
      costs for each strategy. Estimates of optimal marsh-management strategies may
      then be produced, maximizing the "ecosystem benefits per estimated costs" ratio.

PMID- 30110332
TI  - Enhancing motor learning of young soccer players through preventing an internal
      focus of attention: The effect of shoes colour.
AB  - The purpose of this research was to assess how the motor learning skills in 7
      years old soccer players can be improved by preventing an internal focus of
      attention via the use coloured shoes. We painted the classic black soccer shoes
      in six areas corresponding to six regions of the foot with which it is possible
      to interact with the ball. Thirty-four 7-years-old soccer players were randomized
      to two groups (Coloured n = 17 and Black, n = 17) to perform four basic football
      manoeuvres/tasks: reception (RECP), passing (PASS), ball management (MAGT), and
      shooting (SHOT). We found highly significant differences (P<0.001) in all four
      performance tests: mean(sd) RECP: 0.82(0.07) vs. 0.45(0.12); PASS: 0.85(0.07) vs.
      0.47(0.09); MAGT: 0.91(0.09); SHOT: 1.00(1.00) vs. 0.44(0.16). Colored shoes
      appear to draw children's attention away from body centered cues without explicit
      verbal communications. We propose that this cognitive adaptation enhanced the
      technical gesture by preventing the negative processes associated with action
      constraining when adopting an internal focus attention (perhaps by allowing the
      foot to adapt to surfaces and movements more naturally than conditions that
      promote a focus on the body movement). Consequently, this type of coloured
      footwear could be used during childhood to allow children to enhance the
      performance of basic football exercises through preventing action constraining
      and promoting intuitive (non-body centered) action knowledge.

PMID- 30110334
TI  - Analysis of cognitive and attentional profiles in children with and without ADHD
      using an innovative virtual reality tool.
AB  - In previous studies, children with Attention-Deficit Hyperactivity Disorder
      (ADHD) have been found to have more difficulties with processing speed, working
      memory, and attentional tasks. The present study aimed to compare the cognitive
      variables (working memory and processing speed) and the attentional profiles of a
      sample of students with and without ADHD, using scales from the WISC-IV, and the
      virtual reality-based attentional test known as 'Aula Nesplora'; and determine
      the extent to which the aforementioned variables may predict student group
      membership. A total of 88 students took part in this study (66 males and 22
      females), aged from 6 to 16 years (M = 10.20; SD = 2.79). The sample was divided
      into two groups: an ADHD group (n = 50) and a Control group (n = 38). Students in
      the ADHD group obtained lower scores in working memory and in processing speed,
      as well as demonstrating poorer performance in Aula Nesplora than did their
      peers. Working memory, and the number of omissions, were both shown to be
      reliable predictors of group membership. This study revealed the importance of
      obtaining data from attentional variables differentiated by modality when
      considering cognitive variables, in order to better characterize the difficulties
      experienced by individuals diagnosed with ADHD.

PMID- 30110333
TI  - Prognostic factors for return to work and work disability among colorectal cancer
      survivors; A systematic review.
AB  - BACKGROUND: Colorectal cancer is diagnosed progressively in employed patients due
      to screening programs and increasing retirement age. The objective of this study
      was to identify prognostic factors for return to work and work disability in
      patients with colorectal cancer. METHODS: The research protocol was published at
      PROSPERO with registration number CRD42017049757. A systematic review of cohort
      and case-control studies in colorectal cancer patients above 18 years, who were
      employed when diagnosed, and who had a surgical resection with curative intent
      were included. The primary outcome was return to work or work disability.
      Potentially prognostic factors were included in the analysis if they were
      measured in at least three studies. Risk of bias was assessed according to the
      QUality In Prognosis Studies tool. A qualitative synthesis analysis was performed
      due to heterogeneity between studies. Quality of evidence was evaluated according
      to Grading of Recommendation Assessment, Development and Evaluation. RESULTS:
      Eight studies were included with a follow-up period of 26 up to 520 weeks.
      (Neo)adjuvant therapy, higher age, and more comorbidities had a significant
      negative influence on return to work. A previous period of unemployment,
      extensive surgical resection and postoperative complications significantly
      increased the risk of work disability. The quality of evidence for these
      prognostic factors was considered very low to moderate. CONCLUSION: Health care
      professionals need to be aware of these prognostic factors to select patients
      eligible for timely intensified rehabilitation in order to optimize the return to
      work process and prevent work disability.

PMID- 30110335
TI  - Researchers' attitudes to the 3Rs-An upturned hierarchy?
AB  - Animal use in biomedical research is generally justified by its potential
      benefits to the health of humans, or other animals, or the environment. However,
      ethical acceptability also requires scientists to limit harm to animals in their
      research. Training in laboratory animal science (LAS) helps scientists to do this
      by promoting best practice and the 3Rs. This study evaluated scientists'
      awareness and application of the 3Rs, and their approach to other ethical issues
      in animal research. It was based on an online survey of participants in LAS
      courses held in eight venues in four European countries: Portugal (Porto, Braga),
      Germany (Munich, Heidelberg), Switzerland (Basel, Lausanne, Zurich), and Denmark
      (Copenhagen). The survey questions were designed to assess general attitudes to
      animal use in biomedical research, Replacement alternatives, Reduction and
      Refinement conflicts, and harm-benefit analysis. The survey was conducted twice:
      immediately before the course ('BC', N = 310) and as a follow-up six months after
      the course ('AC', N = 127). While courses do appear to raise awareness of the
      3Rs, they had no measurable effect on the existing low level of belief that
      animal experimentation can be fully replaced by non-animal methods. Most
      researchers acknowledged ethical issues with their work and reported that they
      discussed these with their peers. The level of an animal's welfare, and
      especially the prevention of pain, was regarded as the most pressing ethical
      issue, and as more important than the number of animals used or the use of
      animals as such. Refinement was considered more feasible than Replacement, as
      well as more urgent, and was also favoured over Reduction. Respondents in the
      survey reversed the 'hierarchy' of the 3Rs proposed by their architects, Russell
      and Burch, prioritizing Refinement over Reduction, and Reduction over
      Replacement. This ordering may conflict with the expectations of the public and
      regulators.

PMID- 30110336
TI  - Validation of DIABSCORE in screening for Type 2 Diabetes and prediabetes in
      Tunisian population.
AB  - AIMS: To perform a validation of DIABSCORE in a sample of Tunisian adults and
      find out the optimal cut-off point for screening of Type 2 diabetes (T2D) and
      prediabetes. METHODS: 225 adults 18-75 years and a subgroup of 138 adults (18-54
      years), with undiagnosed T2D from the region of Cap-Bon, Tunisia were included in
      the present study. The DIABSCORE was calculated based on: age, waist/height
      ratio, family history of T2D and gestational diabetes. Receiver operating
      characteristics (ROC) curves and areas under curve (AUC) were obtained. The T2D
      and prediabetes prevalences odds ratios (OR) between patients exposed and not
      exposed to DIABSCORE>=90 and DIABSCORE>=80, respectively were calculated in both
      age ranges. RESULTS: For screening of T2D the best value was DIABSCORE = 90 with
      a highest sensitivity (Se), negative predictive value (NPV) and lower negative
      likelihood ratio in participants aged 18-75 yr (Se = 97%; NPV = 97%) when
      compared to participants aged 18-54 yr (Se = 95%; NPV = 97%); for prediabetes,
      the best Se and NPV were for DIABSCORE = 80 in both age groups, but it showed a
      disbalanced sensitivity-specificity. The ROC curves for T2D showed a similar AUC
      in both age ranges (AUC = 0.62 and AUC = 0.61 respectively). The ROC curves for
      prediabetes showed a highest AUC in those aged 18-54 years than the older ones
      (AUC = 0.62 and AUC = 0.57, respectively). The prevalences OR of T2D for
      DIABSCORE>=90 was higher than for DIABSCORE>=80 in both age ranges. Nevertheless,
      the prevalences OR of prediabetes for DIABSCORE>=90 was half of the detected for
      DIABSCORE>=80 in both age ranges. CONCLUSION: The DIABSCORE is a simple clinical
      tool and accurate method in screening for T2D and prediabetes in the adult
      Tunisian population.

PMID- 30110337
TI  - Herpes ICP8 protein stimulates homologous recombination in human cells.
AB  - Recombineering has transformed functional genomic analysis. Genome modification
      by recombineering using the phage lambda Red homologous recombination protein
      Beta in Escherichia coli has approached 100% efficiency. While highly efficient
      in E. coli, recombineering using the Red Synaptase/Exonuclease pair (SynExo) in
      other organisms declines in efficiency roughly correlating with phylogenetic
      distance from E. coli. SynExo recombinases are common to double-stranded DNA
      viruses infecting a variety of organisms, including humans. Human Herpes virus 1
      (HHV1) encodes a SynExo comprised of ICP8 synaptase and UL12 exonuclease. In a
      previous study, the Herpes SynExo was reconstituted in vitro and shown to
      catalyze a model recombination reaction. Here we describe stimulation of gene
      targeting to edit a novel fluorescent protein gene in the human genome using ICP8
      and compared its efficiency to that of a "humanized" version of Beta protein from
      phage lambda. ICP8 significantly enhanced gene targeting rates in HEK 293T cells
      while Beta was not only unable to catalyze recombineering but inhibited gene
      targeting using endogenous recombination functions, despite both synaptases being
      well-expressed and localized to the nucleus. This proof of concept encourages
      developing species-specific SynExo recombinases for genome engineering.

PMID- 30110338
TI  - The binding of Chp2's chromodomain to methylated H3K9 is essential for Chp2's
      role in heterochromatin assembly in fission yeast.
AB  - The binding of heterochromatin protein 1 (HP1) to lysine 9-methylated histone H3
      (H3K9me) is an essential step in heterochromatin assembly. Chp2, an HP1-family
      protein in the fission yeast Schizosaccharomyces pombe, is required for
      heterochromatic silencing. Chp2 recruits SHREC, a multifunctional protein complex
      containing the nucleosome remodeler Mit1 and the histone deacetylase Clr3.
      Although the targeting of SHREC to chromatin is thought to occur via two distinct
      modules regulated by the SHREC components Chp2 and Clr2, it is not clear how
      Chp2's chromatin binding regulates SHREC function. Here, we show that H3K9me
      binding by Chp2's chromodomain (CD) is essential for Chp2's silencing function
      and for SHREC's targeting to chromatin. Cells expressing a Chp2 mutant with
      defective H3K9me binding (Chp2-W199A) have a silencing defect, with a phenotype
      similar to that of chp2-null cells. Genetic analysis using a synthetic silencing
      system revealed that a Chp2 mutant and SHREC-component mutants had similar
      phenotypes, suggesting that Chp2's function also affects SHREC's chromatin
      binding. Size-exclusion chromatography of native protein complexes showed that
      Chp2-CD's binding of H3K9me3 ensures Clr3's chromatin binding, and suggested that
      SHREC's chromatin binding is mediated by separable functional modules.
      Interestingly, we found that the stability of the Chp2 protein depended on the
      Clr3 protein's histone deacetylase activity. Our findings demonstrate that Chp2's
      H3K9me binding is critical for SHREC function and that the two modules within the
      SHREC complex are interdependent.

PMID- 30110339
TI  - Characterization of natural bactericidal antibody against Haemophilus influenzae
      type a in Canadian First Nations: A Canadian Immunization Research Network (CIRN)
      Clinical Trials Network (CTN) study.
AB  - : During the last two decades, Haemophilus influenzae serotype a (Hia) emerged as
      an important cause of invasive disease in Canadian First Nations and Inuit, and
      Alaskan Native populations, with the highest rates reported in young children.
      Immunocompetent adults, in contrast to children, do not typically develop
      invasive Hia disease. To clarify factors responsible for an increased burden of
      invasive Hia disease in certain population groups we studied serum bactericidal
      activity (SBA) against Hia and quantified IgG and IgM specific to Hia capsular
      polysaccharide in healthy adult members of two First Nations communities: 1) with
      reported cases of invasive Hia disease (Northern Ontario, NO), and 2) without
      reported cases (Southern Ontario, SO), in comparison to non-First Nations living
      in proximity to the NO First Nations community, and non-First Nations elderly non
      frail Canadians from across the country (total of 110 First Nations and 76 non
      First Nations). To elucidate the specificity of bactericidal antibodies, sera
      were absorbed with various Hia antigens. Naturally acquired SBA against Hia was
      detected at higher rates in First Nations (NO, 80%; SO, 96%) than non-First
      Nations elderly Canadians (64%); the SBA titres in First Nations were higher than
      in non-First Nations elderly Canadians (P<0.001) and NO non-First Nations adults
      (P>0.05). Among First Nations, SBA was mediated predominantly by IgM, and by both
      antibodies specific to Hia capsular polysaccharide and lipooligosaccharide.
      CONCLUSIONS: The SBA against Hia is frequently present in sera of First Nations
      adults regardless of the burden of Hia disease observed in their community; it
      may represent part of the natural antibody repertoire, which is potentially
      formed in this population under the influence of certain epigenetic factors.
      Although the nature of these antibodies deserves further studies to understand
      their origin, the data suggest that they may represent important protective
      mechanism against invasive Hia disease.

PMID- 30110340
TI  - The fecal microbiome and metabolome differs between dogs fed Bones and Raw Food
      (BARF) diets and dogs fed commercial diets.
AB  - INTRODUCTION: Feeding a Bones and Raw Food (BARF) diet has become an increasing
      trend in canine nutrition. Bones and Raw Food diets contain a high amount of
      animal components like meat, offal, and raw meaty bones, combined with
      comparatively small amounts of plant ingredients like vegetables and fruits as
      well as different sorts of oil and supplements. While many studies have focused
      on transmission of pathogens via contaminated meat and on nutritional imbalances,
      only few studies have evaluated the effect of BARF diets on the fecal microbiome
      and metabolome. The aim of the study was to investigate differences in the fecal
      microbiome and the metabolome between dogs on a BARF diet and dogs on a
      commercial diet (canned and dry dog food). METHODS: Naturally passed fecal
      samples were obtained from 27 BARF and 19 commercially fed dogs. Differences in
      crude protein, fat, fiber, and NFE (Nitrogen-Free Extract) between diets were
      calculated with a scientific nutrient database. The fecal microbiota was analyzed
      by 16S rRNA gene sequencing and quantitative PCR assays. The fecal metabolome was
      analyzed in 10 BARF and 9 commercially fed dogs via untargeted metabolomics
      approach. RESULTS: Dogs in the BARF group were fed a significantly higher amount
      of protein and fat and significantly lower amount of NFE and fiber. There was no
      significant difference in alpha-diversity measures between diet groups. Analysis
      of similarity (ANOSIM) revealed a significant difference in beta-diversity (p <
      0.01) between both groups. Linear discriminant analysis effect size (LefSe)
      showed a higher abundance of Lactobacillales, Enterobacteriaceae, Fusobacterium
      and, Clostridium in the BARF group while conventionally fed dogs had a higher
      abundance of Clostridiaceae, Erysipelotrichaceae, Ruminococcaceae, and
      Lachnospiraceae. The qPCR assays revealed significantly higher abundance of
      Escherichia coli (E. coli) and Clostridium (C.). perfringens and an increased
      Dysbiosis Index in the BARF group. Principal component analysis (PCA) plots of
      metabolomics data showed clustering between diet groups. Random forest analysis
      showed differences in the abundance of various components, including increased 4
      hydroxybutryric acid (GBH) and 4-aminobutyric acid (GABA) in the BARF group.
      Based on univariate statistics, several metabolites were significantly different
      between diet groups, but lost significance after adjusting for multiple
      comparison. No differences were found in fecal bile acid concentrations, but the
      BARF group had a higher fecal concentration of cholesterol in their feces
      compared to conventionally fed dogs. CONCLUSION: Microbial communities and
      metabolome vary significantly between BARF and commercially fed dogs.

PMID- 30110342
TI  - Trypanosoma brucei triggers a marked immune response in male reproductive organs.
AB  - African trypanosomiasis is caused by the protozoan parasite Trypanosoma brucei,
      transmitted between mammals by the bite of a tsetse. It has been recently shown
      that parasites accumulate in large numbers in various organs and tissues,
      including the mouse testis. Whether parasites are protected from the immune
      system in the male reproductive organ or can be transmitted through sexual route
      remains unknown. Here we show that parasites can be detected by fine needle
      aspiration cytology of the male reproductive system in mice, and
      histopathological analysis revealed that T. brucei accumulates in the stroma of
      the epididymis, epididymal adipose tissue and fibrous tunics of the testis. No
      parasites were found in the lumen of intact epididymal ducts or seminiferous
      tubules of the testis, indicating that the large majority of the parasites are
      not located in immune-privileged sites. In fact, these parasites are associated
      with marked inflammatory cell infiltration, parasite degeneration, and severe
      tissue damage and rupture of epididymal ducts, which may be related with reduced
      fertility. Overall, we show that just like in the bloodstream and most other
      tissues, in the male reproductive organs, T. brucei are exposed to a strong
      immune response. The detection of a very high number of parasites in this organ
      and its accessibility opens the possibility of using fine needle aspiration
      cytology as a complementary diagnostic tool in Animal African Trypanosomiasis.

PMID- 30110343
TI  - Time-restricted feeding suppresses excess sucrose-induced plasma and liver lipid
      accumulation in rats.
AB  - The etiology of metabolic syndrome involves several complicated factors. One of
      the main factors contributing to metabolic syndrome has been proposed to be
      excessive intake of sucrose, which disturbs hepatic lipid metabolism, resulting
      in fatty liver. However, the mechanism by which sucrose induces fatty liver
      remains to be elucidated. Considering feeding behavior important for metabolism,
      we investigated whether time-restricted feeding of high sucrose diet (HSD), only
      in the active phase (the dark phase of the daily light/dark cycle), would
      ameliorate adverse effects of sucrose on lipid homeostasis in rats. Male Wistar
      rats, fed either an ad libitum (ad lib.) or time-restricted control starch diet
      (CD) or HSD were investigated. Rats fed ad lib. (CD and HSD) completed
      approximately 20% of food intake in the daytime. Time-restricted feeding did not
      significantly suppress total food intake of rats. However, time-restricted
      feeding of HSD significantly suppressed the increased plasma triglyceride levels.
      Moreover, time-restricted feeding also ameliorated HSD-induced liver lipid
      accumulation, whereas circadian oscillations of liver clock gene or
      transcriptional factor gene expression for lipid metabolism were not altered
      significantly. These results demonstrated that restricting sucrose intake only
      during the active phase in rats ameliorates the abnormal lipid metabolism caused
      by excess sucrose intake.

PMID- 30110341
TI  - Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet.
AB  - Annexin A6 (AnxA6) controls cholesterol and membrane transport in endo- and
      exocytosis, and modulates triglyceride accumulation and storage. In addition,
      AnxA6 acts as a scaffolding protein for negative regulators of growth factor
      receptors and their effector pathways in many different cell types. Here we
      investigated the role of AnxA6 in the regulation of whole body lipid metabolism
      and insulin-regulated glucose homeostasis. Therefore, wildtype (WT) and AnxA6
      knockout (KO) mice were fed a high-fat diet (HFD) for 17 weeks. During the course
      of HFD feeding, AnxA6-KO mice gained less weight compared to controls, which
      correlated with reduced adiposity. Systemic triglyceride and cholesterol levels
      of HFD-fed control and AnxA6-KO mice were comparable, with slightly elevated high
      density lipoprotein (HDL) and reduced triglyceride-rich lipoprotein (TRL) levels
      in AnxA6-KO mice. AnxA6-KO mice displayed a trend towards improved insulin
      sensitivity in oral glucose and insulin tolerance tests (OGTT, ITT), which
      correlated with increased insulin-inducible phosphorylation of protein kinase B
      (Akt) and ribosomal protein S6 kinase (S6) in liver extracts. However, HFD-fed
      AnxA6-KO mice failed to downregulate hepatic gluconeogenesis, despite similar
      insulin levels and insulin signaling activity, as well as expression profiles of
      insulin-sensitive transcription factors to controls. In addition, increased
      glycogen storage in livers of HFD- and chow-fed AnxA6-KO animals was observed.
      Together with an inability to reduce glucose production upon insulin exposure in
      AnxA6-depleted HuH7 hepatocytes, this implicates AnxA6 contributing to the fine
      tuning of hepatic glucose metabolism with potential consequences for the systemic
      control of glucose in health and disease.

PMID- 30110344
TI  - Outcomes of Trypanosoma cruzi and Trypanosoma evansi infections on health of
      Southern coati (Nasua nasua), crab-eating fox (Cerdocyon thous), and ocelot
      (Leopardus pardalis) in the Brazilian Pantanal.
AB  - The occurrence of Trypanosoma spp. in wild carnivore populations has been
      intensively investigated during the last decades. However, the impact of these
      parasites on the health of free-living infected animals has been largely
      neglected. The Pantanal biome is the world's largest seasonal wetland, harboring
      a great diversity of species and habitats. This includes 174 species of mammals,
      of which 20 belong to the order Carnivora. The present study aimed to investigate
      the effect of Trypanosoma evansi and Trypanosoma cruzi infections and
      coinfections on the health of the most abundant carnivores in the Pantanal: coati
      (Nasua nasua), crab-eating fox (Cerdocyon thous), and ocelot (Leopardus
      pardalis). We captured 39 coatis, 48 crab-eating foxes, and 19 ocelots.
      Diagnostic tests showed T. cruzi infection in 7 crab-eating foxes and 5 coatis.
      Additionally, 7 crab-eating foxes, 10 coatis, and 12 ocelots were positive for T.
      evansi. We observed coinfections in 9 crab-eating foxes, 8 coatis, and 2 ocelots.
      This is the first report of T. evansi and T. cruzi infection on the health of
      free-living ocelots and crab-eating foxes. We showed that single T. evansi or T.
      cruzi infection, as well as coinfection, caused some degree of anemia in all
      animals, as well as an indirect negative effect on body condition in coatis and
      crab-eating foxes via anemia indicators and immune investment, respectively.
      Furthermore, the vigorous immune investment observed in sampled coatis, crab
      eating foxes and ocelots infected by T. evansi, T. cruzi and coinfected can be
      highly harmful to their health. Overall, our results indicate that single and
      combined infection with T. evansi and T. cruzi represent a severe risk to the
      health of wild carnivores in the Pantanal region.

PMID- 30110345
TI  - Genome-driven evaluation and redesign of PCR tools for improving the detection of
      virulence-associated genes in aeromonads.
AB  - Many virulence factors have been described for opportunistic pathogens within the
      genus Aeromonas. Polymerase Chain Reactions (PCRs) are commonly used in
      population studies of aeromonads to detect virulence-associated genes in order to
      better understand the epidemiology and emergence of Aeromonas from the
      environment to host, but their performances have never been thoroughly evaluated.
      We aimed to determine diagnostic sensitivity and specificity of PCR assays for
      the detection of virulence-associated genes in a collection of Aeromonas isolates
      representative for the genetic diversity in the genus. Thirty-nine Aeromonas
      strains belonging to 27 recognized species were screened by published PCR assays
      for virulence-associated genes (act, aerA, aexT, alt, ascFG, ascV, ast, lafA,
      lip, ser, stx1, stx2A). In parallel, homologues of the 12 putative virulence
      genes were searched from the genomes of the 39 strains. Of the 12 published PCR
      assays for virulence factors, the comparison of PCR results and genome analysis
      estimated diagnostic sensitivities ranging from 34% to 100% and diagnostic
      specificities ranged from 71% to 100% depending upon the gene. To improve the
      detection of virulence-associated genes in aeromonads, we have designed new
      primer pairs for aerA/act, ser, lafA, ascFG and ascV, which showed excellent
      diagnostic sensitivity and specificity. Altogether, the analysis of high quality
      genomic data, which are more and more easy to obtain, provides significant
      improvements in the genetic detection of virulence factors in bacterial strains.

PMID- 30110346
TI  - Type 2 diabetic patients on renal replacement therapy: Probability to receive
      renal transplantation and survival after transplantation.
AB  - BACKGROUND: Type 2 diabetic (T2DM) patients on renal replacement therapy (RRT)
      seldom receive a kidney transplant, which is partly due to age and comorbidities.
      Adjusting for case mix, we investigated whether T2DM patients have equal
      opportunity for renal transplantation compared to other patients on dialysis, and
      whether survival after transplantation is comparable. METHODS: Patients who
      entered RRT in Finland in 2000-2010 (n = 5419) were identified from the Finnish
      Registry for Kidney Diseases and followed until the end of 2012. Of these, 20%
      had T2DM, 14% type 1 diabetes (T1DM) and 66% other than diabetes as the cause of
      ESRD. Uni-/multivariate survival analysis techniques were employed to assess the
      probability of kidney transplantation after the start of dialysis and survival
      after transplantation. RESULTS: T2DM patients had a relative probability of renal
      transplantation of 0.18 (95% CI 0.15-0.22, P<0.001) compared to T1DM patients:
      this increased to 0.51 (95% CI 0.36-0.72, P<0.001) after adjustment for case mix
      (age, gender, laboratory values and comorbidities). When T2DM patients were
      compared to non-diabetic patients, the corresponding relative probabilities were
      0.25 (95% CI 0.20-0.30, P<0.001) and 0.59 (95% CI 0.43-0.83, P = 0.002). After
      renal transplantation when adjusted for age and gender, relative risk of death
      was 1.25 (95% CI 0.64-2.44, P = 0.518) for T1DM patients and 0.72 (0.43-1.22, P =
      0.227) for other patients compared to T2DM patients. CONCLUSIONS: T2DM patients
      had a considerably lower probability of receiving a kidney transplant, which
      could not be fully explained by differences in the patient characteristics.
      Survival within 5 years after transplantation is comparably good in T2DM
      patients.

PMID- 30110347
TI  - Optimization of fluorophores for chemical tagging and immunohistochemistry of
      Drosophila neurons.
AB  - The use of genetically encoded 'self-labeling tags' with chemical fluorophore
      ligands enables rapid labeling of specific cells in neural tissue. To improve the
      chemical tagging of neurons, we synthesized and evaluated new fluorophore ligands
      based on Cy, Janelia Fluor, Alexa Fluor, and ATTO dyes and tested these with
      recently improved Drosophila melanogaster transgenes. We found that tissue
      clearing and mounting in DPX substantially improves signal quality when combined
      with specific non-cyanine fluorophores. We compared and combined this labeling
      technique with standard immunohistochemistry in the Drosophila brain.

PMID- 30110349
TI  - A supplier selection model in pharmaceutical supply chain using PCA, Z-TOPSIS and
      MILP: A case study.
AB  - Supplier selection is one of the critical processes in supplier chain management
      which is associated with the flow of goods and services from the supplier of raw
      material to the final consumer. The purpose of this paper is to present a novel
      approach and improves the supplier selection in a multi-item/multi-supplier
      environment, and provide the importance and the reliability of the criteria by
      handling vagueness and imperfection of information in decision making process.
      First, principal component analysis (PCA) method is used to reduce the number of
      supplier selection criteria in pharmaceutical companies. Next, using the most
      important criteria resulted from the PCA method, the importance and the
      reliability of the selected criteria are assessed by a group of decision-maker
      (DM). Then, the importance value of each supplier with respect to each product is
      obtained via the Technique for Order Performance by Similarity to Ideal Solution
      (TOPSIS) based on the concept of Z-numbers called Z-TOPSIS. Finally, these values
      are used as inputs in a mixed integer linear programming (MILP) to determine the
      suppliers and the amount of the products provided from the related suppliers. To
      validate the proposed methodology, an application is performed in a
      pharmaceutical company. The results show that the proposed method could provide
      promising results in decision making process more appropriately.

PMID- 30110348
TI  - Differences in clinical features and dengue severity between local and migrant
      Chinese with dengue infection in Singapore.
AB  - Dengue is endemic in Singapore but not China. We compared clinical features and
      disease severity of dengue between local and migrant Chinese, most of whom were
      construction workers, in Singapore. A retrospective study with all hospitalized
      dengue patients from 2005 to 2008 were performed, including 2609 local and 1195
      migrant Chinese. Compared with local Chinese, migrant Chinese were younger. There
      were more males, but fewer had comorbidities. Migrant Chinese had more headache,
      eye pain, nausea and myalgia. They had significantly lower median leukocyte
      count, ALT and AST, and higher platelet count nadir. Among warning signs, migrant
      Chinese had significantly less persistent vomiting, clinical fluid accumulation,
      hepatomegaly, hematocrit rise with rapid platelet drop, and more mucosal
      bleeding. Adjusted for age, gender and comorbidities, migrant Chinese were
      significantly at higher risk of dengue hemorrhagic fever (DHF) (adjusted odds
      ratio [aOR]: 1.20, 95% confidence interval [CI]: 1.03-1.41) and dengue shock
      syndrome (aOR: 1.49, 95% CI: 1.06-2.10), and had longer hospitalization (beta
      coefficient value: 0.27, 95%CI: 0.09-0.44, p = 0.003). There was 1 death among
      migrant Chinese and 2 deaths among local Chinese. We documented differences in
      clinical and laboratory features, and dengue severity between local and migrant
      Chinese in Singapore. Migrant Chinese may need more medical attention given
      higher risk of DHF.

PMID- 30110350
TI  - In spite of the system: A qualitatively-driven mixed methods analysis of the
      mental health services experiences of LGBTQ people living in poverty in Ontario,
      Canada.
AB  - Lesbian, gay, bisexual, trans, and/or queer (LGBTQ) people face barriers to
      accessing mental health care; however, we know little about service experiences
      of low income LGBTQ people. In this qualitatively-driven mixed methods study,
      over 700 women and/or trans people completed an internet survey, of whom 12 LGBTQ
      individuals living in poverty participated in interviews. Low income LGBTQ
      respondents saw more mental health professionals and had more unmet need for care
      than all other LGBTQ/income groups. Narrative analysis illustrated the work
      required to take care of oneself in the context of extreme financial constraints.
      These findings highlight the mechanisms through which inadequate public sector
      mental health services can serve to reproduce and sustain both poverty and health
      inequities.

PMID- 30110352
TI  - Warming in the Arctic Captured by productivity variability at an Arctic Fjord
      over the past two centuries.
AB  - Arctic fjords feature among some of the most climate-sensitive regions on the
      planet. The site of this study-Kongsfjorden-is one such fjord in which
      sedimentation and sediment geochemistry reflect climate-mediated changes in
      glacial melt and marine primary productivity. Here, we have shown that the fjord
      is particularly sensitive to the changing melt dynamics of the surrounding
      glaciers which are a direct consequence of warming/cooling in the region and is
      reflected in the productivity at the fjord. Warming increases meltwater influx
      into the fjord leading to enhanced turbidity which results in lower productivity.
      A multi-proxy study (sedimentary organic matter content, carbon and nitrogen
      isotope ratios, and microfossil abundance) using a 21 cm long sediment core from
      the Kongsfjorden helped us reconstruct warming driven melt-dynamics history for
      the past two centuries. Proxy data show a general decreasing trend in
      productivity along with a few excursions over the last two centuries. Warming
      driven glacial-melt dynamics appears to be the dominant control on productivity
      throughout the span of the core.

PMID- 30110351
TI  - Spatial and temporal trends in the fate of silver nanoparticles in a whole-lake
      addition study.
AB  - Studies of the fate and toxicity of nanoparticles, including nanosilver (AgNPs),
      have been primarily conducted using bench scale studies over relatively short
      periods of time. To better understand the fate of AgNPs in natural aquatic
      ecosystems over longer time scales and ecological settings, we released
      suspensions of AgNPs (30-50 nm, capped with polyvinylpyrrolidone) into a boreal
      lake at the Experimental Lakes Area in Canada. Approximately 9 kg of silver was
      added from a shoreline point source from June to October 2014, which resulted in
      total Ag (TAg) concentrations of about 10 MUg L-1 or less. In addition, dissolved
      Ag concentrations (DAg) were typically very low. Using single particle
      inductively coupled plasma mass spectrometry (sp-ICP-MS) analysis of grab
      samples, we found that the nanoparticles typically ranged in the 40-60 nm size
      class and were widely distributed throughout the lake, while larger aggregates
      (i.e. >100 nm) were infrequently detected. The highest occurrence of aggregates
      was found near the addition site; however, size distributions did not vary
      significantly among spatial locations or time suggesting rapid dispersal upon
      entry into the lake. Lake stratification at the thermocline was not a barrier to
      mobility of the AgNPs, as the particles were also detected in the hypolimnion.
      Environmental factors influenced Ag size distributions over sampling locations
      and time. Total dissolved phosphorus, bacterioplankton chlorophyll-a, and
      sampling time strongly correlated with aggregation and dissolution dynamics.
      AgNPs thus appear to be relatively mobile and persistent over the growing season
      in lake ecosystems.

PMID- 30110353
TI  - Automated quantification of low amplitude rhythmic contractions (LARC) during
      real-world urodynamics identifies a potential detrusor overactivity subgroup.
AB  - OBJECTIVES: Detrusor overactivity (DO) is characterized by non-voiding detrusor
      smooth muscle contractions during the bladder filling phase and often contributes
      to overactive bladder. In some patients DO is observed as isolated or sporadic
      contractions, while in others DO is manifested as low amplitude rhythmic
      contractions (LARC). The aim of this study was to develop an objective method to
      quantify LARC frequencies and amplitudes in urodynamic studies (UDS) and identify
      a subgroup DO of patients with LARC. METHODS: An automated Fast Fourier Transform
      (FFT) algorithm was developed to analyze a 205-second region of interest of
      retrospectively collected "real-world" UDS ending 30 seconds before voiding. The
      algorithm was designed to identify the three largest rhythmic amplitude peaks in
      vesical pressure (Pves) in the 1.75-6 cycle/minute frequency range. These peak
      Pves amplitudes were analyzed to determine whether they were 1) significant
      (above baseline Pves activity) and 2) independent (distinct from any in abdominal
      pressure (Pabd) rhythm). RESULTS: 95 UDS met criteria for inclusion and were
      analyzed with the FFT algorithm. During a blinded visual analysis, a
      neurourologist/urodynamicist identified 52/95 (55%) patients as having DO. The
      FFT algorithm identified significant and independent (S&I) LARC in 14/52 (27%)
      patients with DO and 0/43 patients (0%) without DO, resulting in 100% specificity
      and a significant association (Fischer's exact test, p<0.0001). The average
      slowest S&I LARC frequency in this DO subgroup was 3.20+/-0.34 cycles/min with an
      amplitude of 8.40+/-1.30 cm-H2O. This algorithm can analyze individual UDS in
      under 5 seconds, allowing real-time interpretation. CONCLUSIONS: An FFT algorithm
      can be applied to "real-world" UDS to automatically characterize the frequency
      and amplitude of underlying LARC. This algorithm identified a potential subgroup
      of DO patients with LARC.

PMID- 30110354
TI  - Antidepressive and anxiolytic effects of ostruthin, a TREK-1 channel activator.
AB  - We screened a library of botanical compounds purified from plants of Vietnam for
      modulators of the activity of a two-pore domain K+ channel, TREK-1, and we
      identified a hydroxycoumarin-related compound, ostruthin, as an activator of this
      channel. Ostruthin increased whole-cell TREK-1 channel currents in 293T cells at
      a low concentration (EC50 = 5.3 MUM), and also activity of the TREK-2 channel
      (EC50 = 3.7 mM). In contrast, ostruthin inhibited other K+ channels, e.g. human
      ether-a-go-go-related gene (HERG1), inward-rectifier (Kir2.1), voltage-gated
      (Kv1.4), and two-pore domain (TASK-1) at higher concentrations, without affecting
      voltage-gated potassium channel (KCNQ1 and 3). We tested the effect of this
      compound on mouse anxiety- and depression-like behaviors and found anxiolytic
      activity in the open-field, elevated plus maze, and light/dark box tests. Of
      note, ostruthin also showed antidepressive effects in the forced swim and tail
      suspension tests, although previous studies reported that inhibition of TREK-1
      channels resulted in an antidepressive effect. The anxiolytic and antidepressive
      effect was diminished by co-administration of a TREK-1 blocker, amlodipine,
      indicating the involvement of TREK-1 channels. Administration of ostruthin
      suppressed the stress-induced increase in anti-c-Fos immunoreactivity in the
      lateral septum, without affecting immunoreactivity in other mood disorder-related
      nuclei, e.g. the amygdala, paraventricular nuclei, and dorsal raphe nucleus.
      Ostruthin may exert its anxiolytic and antidepressive effects through a different
      mechanism from current drugs.

PMID- 30110356
TI  - A dynamic bid price approach for the seat inventory control problem in railway
      networks with consideration of passenger transfer.
AB  - Railway seat inventory control aims to maximize ticket sale profits by
      determining a selling policy on the reservation horizon. This paper introduces a
      dynamic bid price approach in railway seat inventory control problem. Multi
      dimensional demand is taken into consideration in modeling the problem, in which
      passenger transfer is our main focus. A new approximate approach is designed to
      this problem. Numerical examples are presented to evaluate the efficiency of this
      approach. Simulation experiments are conducted to verify the impact of transfer
      under different scenarios.

PMID- 30110355
TI  - Striatal transcriptome of a mouse model of ADHD reveals a pattern of synaptic
      remodeling.
AB  - Despite the prevalence and high heritability of Attention-Deficit/Hyperactivity
      Disorder (ADHD), genetic etiology remains elusive. Clinical evidence points in
      part to reduced function of the striatum, but which specific genes are
      differentially expressed and how they sculpt striatal physiology to predispose
      ADHD are not well understood. As an exploratory tool, a polygenic mouse model of
      ADHD was recently developed through selective breeding for high home cage
      activity. Relative to the Control line, the High-Active line displays
      hyperactivity and motor impulsivity which are ameliorated with amphetamine. This
      study compared gene expression in the striatum between Control and High-Active
      mice to develop a coherent hypothesis for how genes might affect striatal
      physiology and predispose ADHD-like symptoms. To this end, striatal
      transcriptomes of High-Active and Control mice were analyzed after mice were
      treated with saline or amphetamines. The pseudogene Gm6180 for n-cofilin (Cfl1)
      displayed 20-fold higher expression in High-Active mice corresponding with
      reduced Cfl1 expression suggesting synaptic actin dysregulation. Latrophilin 3
      (Lphn3), which is associated with ADHD in human populations and is involved in
      synapse structure, and its ligand fibronectin leucine rich transmembrane protein
      3 (Flrt3), were downregulated in High-Active mice. Multiple genes were altered in
      High-Active mice in a manner predicted to downregulate the canonical Wnt pathway.
      A smaller and different set of genes including glyoxalase (Glo1) were
      differentially regulated in High-Active as compared to Control in response to
      amphetamine. Together, results suggest genes involved in excitatory synapse
      regulation and maintenance are downregulated in ADHD-like mice. Consistent with
      the molecular prediction, stereological analysis of the striatum from a separate
      set of mice processed for imunohistochemical detection of synaptophysin revealed
      approximately a 46% reduction in synaptophysin immunoreactivity in High-Active
      relative to Control. Results provide a new set of molecular targets related to
      synapse maintenance for the next generation of ADHD medicines.

PMID- 30110359
TI  - Development and testing of a standardized method to estimate honeydew production.
AB  - Honeydew production by Hemiptera is an ecologically important process that
      facilitates mutualisms and increases nutrient cycling. Accurate estimates of the
      amount of honeydew available in a system are essential for quantifying food web
      dynamics, energy flow, and the potential growth of sooty mould that inhibits
      plant growth. Despite the importance of honeydew, there is no standardized method
      to estimate its production when intensive laboratory testing is not feasible. We
      developed two new models to predict honeydew production, one based on insect body
      mass and taxonomic family, and one based on body mass and life stage. We tested
      the accuracy of both models' predictions for a diverse range of honeydew
      producing hemipteran families (Aphididae, Pseudococcidae, Coccidae, Psyllidae,
      Aleyrodidae, Delphacidae, Cicadellidae). The method based on body mass and family
      provided more accurate estimates of honeydew production, due to large variation
      in honeydew production among families. We apply our methodology to a case study,
      the recalculation of honeydew available to invasive red imported fire ant
      (Solenopsis invicta) in the United States. We find that the amount of honeydew
      may be an order of magnitude lower than that previously estimated (2.16 versus
      21.6 grams of honeydew per day) and discuss possible reasons for the difference.
      We anticipate that being able to estimate honeydew production based on minimal
      biological information will have applications to agriculture, invasion biology,
      forestry, and carbon farming.

PMID- 30110358
TI  - Reducing violence by teachers using the preventative intervention Interaction
      Competencies with Children for Teachers (ICC-T): A cluster randomized controlled
      trial at public secondary schools in Tanzania.
AB  - The high global prevalence of school violence underlines the need for prevention.
      However, there are few scientifically evaluated intervention approaches that aim
      at preventing violence by teachers. We evaluated the feasibility and efficacy of
      the preventative intervention Interaction Competencies with Children for Teachers
      (ICC-T). In a cluster randomized controlled trial we assessed attitudes towards
      and use of violence by teachers (self-reported and reported by students) at eight
      schools in four regions in Tanzania. Two regions were randomly assigned as
      intervention regions. Data were assessed in the months before and three months
      after intervention. In total, 158 teachers (58% females; age: 32.08 years, SD =
      5.65) and 486 students (54% females; age: 15.61 years, SD = 0.89) participated in
      this study. The feasibility was very good: Participants' acceptance was high and
      they reported a good integration of the core elements in their working routine.
      The significantly stronger decrease in the use of emotional and physical violence
      reported both by teachers and students as well as the stronger decrease in
      positive attitudes of teachers towards physical and emotional violence in the
      intervention schools at follow-up provide initial evidence of the efficacy.
      However, further evidence for the sustainability of its effect is needed.

PMID- 30110357
TI  - Genomic characterization of NDM-1 and 5, and OXA-181 carbapenemases in
      uropathogenic Escherichia coli isolates from Riyadh, Saudi Arabia.
AB  - Urinary tract infections (UTIs) associated with Escherichia coli are a growing
      threat with an increase in the prevalence of multidrug resistant (MDR) strains,
      particularly beta-lactamase producers, occurring globally. We investigated the
      presence of carbapenem-resistant uropathogenic E. coli clones in community
      acquired UTIs in Riyadh, Kingdom of Saudi Arabia (KSA) to identify the virulence
      and resistance structures of the resistant clones and relate the isolates to
      those circulating globally. A combination of comparative genomics and phenotypic
      approaches were used to characterize ten MDR-uropathogenic Escherichia coli
      isolates recovered from UTI patients in Riyadh between November 2014 and January
      2015. We report the presence of NDM-1 and 5, and OXA-181 in carbapenem-resistant
      UPEC strains from Riyadh, KSA. Single nucleotide polymorphism analyses
      demonstrated that these ten isolates fell into four phylogenetically distinct
      clades within the UPEC phylogeny. Comparative genomic analyses indicate that
      these diverse clones could be distinguished according to their multilocus
      sequencing type (MLST), serology, and virulence and antimicrobial gene
      architectures. These clones include the blaNDM-1 carrying isolates of the
      globally predominant MDR ST131 and ST69 types, previously identified as one of
      the most common UPEC strains in KSA. This is in addition to clones of ST23Cplx
      (ST410) and ST448Cplx (ST448) that have likely evolved from common intestinal
      strains, carrying copies of beta-lactamase genes including blaNDM-5, blaCTX-M-15,
      blaTEM-1, blaCMY-42, blaOXA-1 and blaOXA-181. These data have identified an
      emerging public health concern and highlight the need to use comprehensive
      approaches to detect the structure of MDR E. coli populations associated with
      community-acquired UTIs in KSA.

PMID- 30110360
TI  - Foraging connections: Patterns of prey use linked to invasive predator diel
      movement.
AB  - Invasive predators can profoundly impact native communities, especially in
      insular ecosystems where functionally equivalent predators were evolutionarily
      absent. Beyond direct consumption, predators can affect communities indirectly by
      creating or altering food web linkages among existing species. Where invasive
      predators consume prey from multiple distinct resource channels, novel links may
      couple the dynamics of disjunct modules and create indirect interactions between
      them. Our study focuses on invasive populations of Eleutherodactylus coqui
      (Anura: Leptodactylidae) on Hawaii Island. Coqui actively forage in the
      understory and lower canopy at night but return to the forest floor and
      belowground retreats by day. Recent dietary studies using gut contents and
      naturally occurring stable isotopes indicate higher than expected consumption of
      litter arthropods, which in these Hawaiian forests are primarily non-native
      species. We used laboratory studies to observe diurnal and nocturnal foraging
      behavior, and experimental field additions of C4 vegetation as a litter tracer to
      distinguish epigaeic sources from food web pools in the C3 canopy. Lab trials
      revealed that prey consumption during diurnal foraging was half that consumed
      during nocturnal foraging. Analysis of delta13C isotopes showed incorporation of
      C4 carbon into litter arthropods within one month, and Bayesian mixing models
      estimated that 15-25% of the carbon in coqui tissue was derived from litter
      sources. These results support recent findings that E. coqui are not quiescent
      diurnally but instead actively forage. Such activity by a mobile invasive
      predator may introduce a novel linkage that integrates detrital and foliar
      resource pools, potentially distributing influences of invasive litter arthropods
      through the broader system to amplify impacts on native species.

PMID- 30110362
TI  - Osteology of the first skull of Aetosauroides scagliai Casamiquela 1960
      (Archosauria: Aetosauria) from the Upper Triassic of southern Brazil
      (Hyperodapedon Assemblage Zone) and its phylogenetic importance.
AB  - Aetosauria, which includes 30 species, is a diverse group of armored
      pseudosuchian archosaurs restricted to Upper Triassic beds. Three species occur
      in Brazil, and one of these, Aetosauroides scagliai Casamiquela, 1960, also
      occurs in Argentina. The specimen UFSM 11505, found at Faixa Nova-Cerrito I
      Outcrop, Santa Maria Formation (Hyperodapedon Assemblage Zone), Santa Maria, Rio
      Grande do Sul State, Brazil, is here referred to as Aetosauroides scagliai. This
      specimen preserves most of the skull with both hemimandibles in association with
      most of the postcranium, thus representing one of the most complete aetosaur
      skeletons found in Brazil. The premaxilla, one of the key elements of the cranial
      morphology of aetosaurs, along with the posterior portion of the mandible, was
      not described until now for A. scagliai. In contrast to the typothoracinae
      aetosaurs, the premaxilla of UFSM 11505 presents a shovel-shaped tip, but it is
      not as prominent as the lateral expansion of desmatosuchian aetosaurs, including
      both species of Stagonolepis, S. robertsoni Agassiz, 1844 and S. olenkae Sulej,
      2010. The retroarticular process of the mandible is elongate and not tall, as in
      Stenomity huangae Small & Martz, 2013 and other typothoracinae aetosaurs. Unlike
      previous descriptions of A. scagliai, the maxillary teeth are recurved ziphodont
      like with serrations on the entire length of both margins. Premaxillary teeth are
      also present, being less recurved than the maxillary teeth and cylindrical. We
      recovered Aetosauroides scagliai as the most basal taxon within Aetosauria, like
      previous phylogenetic analyses. Furthermore, our analyses reinforce that recurved
      and unconstricted maxillary teeth, the shovel-shaped premaxilla and the presence
      of a tuber on the surangular are plesiomorphic features of Aetosauria.

PMID- 30110361
TI  - Cellular reagents for diagnostics and synthetic biology.
AB  - We have found that the overproduction of enzymes in bacteria followed by their
      lyophilization leads to 'cellular reagents' that can be directly used to carry
      out numerous molecular biology reactions. We demonstrate the use of cellular
      reagents in a variety of molecular diagnostics, such as TaqMan qPCR with no
      diminution in sensitivity, and in synthetic biology cornerstones such as the
      Gibson assembly of DNA fragments, where new plasmids can be constructed solely
      based on adding cellular reagents. Cellular reagents have significantly reduced
      complexity and cost of production, storage and implementation, features that
      should facilitate accessibility and use in resource-poor conditions.

PMID- 30110363
TI  - Investigating the use of sensor-based IoET to facilitate learning for children in
      rural Thailand.
AB  - A novel sensor-based Internet of Educational Things (IoET) platform named OBSY
      was iteratively designed, developed and evaluated to support education in rural
      regions in Thailand. To assess the effectiveness of this platform, a study was
      carried out at four primary schools located near the Thai northern border with
      244 students and 8 teachers. Participants were asked to carry out three science
      based learning activities and were measured for improvements in learning outcome
      and learning engagement. Overall, the results showed that students in the IoET
      group who had used OBSY to learn showed significantly higher learning outcome and
      had better learning engagement than those in the control condition. In addition,
      for those in the IoET group, there was no significant effect regarding gender,
      home location (Urban or Rural), age, prior experience with technology and
      ethnicity on learning outcome. For learning engagement, only age was found to
      influence interest/enjoyment. The study demonstrated the potential of IoET
      technologies in underprivileged area, through a co-design approach with teachers
      and students, taking into account the local contexts.

PMID- 30110364
TI  - Effect of age at initiation of antiretroviral therapy on treatment outcomes; A
      retrospective cohort study at a large HIV clinic in southwestern Uganda.
AB  - BACKGROUND: The prevalence of HIV infection among older persons is increasing yet
      older age at initiation of antiretroviral therapy (ART) may be associated with
      poorer treatment outcomes including mortality. However, majority of these studies
      have been done in the western world and there is limited data in resource limited
      settings. Our study used routinely collected health facility data to assess
      trends in age at initiation of ART, the effect of age at ART initiation on
      mortality and immunological response at a large urban hospital in south western
      Uganda. METHODS: We conducted a retrospective records review of patients
      attending the HIV clinic at Mbarara Regional Referral Hospital in western Uganda.
      We retrieved records for 8,533 patients who started ART between January 2006 and
      December 2012. Their data had been collected and stored as part of the larger
      International Epidemiological Database for the Evaluation of AIDS (IeDEA). Age
      was stratified into three categories namely; 18-34 (young adults), 35-49 (mid
      age) and 50 years or older (older adults). Survival analysis procedures with
      Kaplan-Meier's plots were used to calculate the survival probability with
      mortality as the endpoint and Poisson regression analysis used to determine the
      adjusted relative risks (RR) of mortality. RESULTS: The proportion of young
      adults and patients at WHO stage I initiating ART increased steadily over the 7
      year period. Older age at ART initiation (> = 50 years) was associated with a
      higher risk of mortality with adjusted relative risk (RR) at 1.63, (95% CI 1.26
      2.11) compared to younger age. Male gender, WHO stages III and IV, lower CD4
      count and lower body mass index were also all independently and significantly
      associated with higher risk for mortality. Older adults also had a poorer
      immunological response RR = 1.79 (95% CI 0.89-3.58) but was not statistically
      significant. CONCLUSIONS: Following ART initiation, older adults compared to the
      young, have a higher risk of mortality. This age group should be targeted first
      for 'screen and treat' approach. Optimization of ART treatment regimens for this
      age group is also required to reduce mortality and improve immunological
      response.

PMID- 30110365
TI  - Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox
      control of 15-lipoxygenase.
AB  - Ferroptosis is a form of programmed cell death associated with inflammation,
      neurodegeneration, and ischemia. Vitamin E (alpha-tocopherol) has been reported
      to prevent ferroptosis, but the mechanism by which this occurs is controversial.
      To elucidate the biochemical mechanism of vitamin E activity, we systematically
      investigated the effects of its major vitamers and metabolites on lipid oxidation
      and ferroptosis in a striatal cell model. We found that a specific endogenous
      metabolite of vitamin E, alpha-tocopherol hydroquinone, was a dramatically more
      potent inhibitor of ferroptosis than its parent compound, and inhibits 15
      lipoxygenase via reduction of the enzyme's non-heme iron from its active Fe3+
      state to an inactive Fe2+ state. Furthermore, a non-metabolizable isosteric
      analog of vitamin E which retains antioxidant activity neither inhibited 15
      lipoxygenase nor prevented ferroptosis. These results call into question the
      prevailing model that vitamin E acts predominantly as a non-specific lipophilic
      antioxidant. We propose that, similar to the other lipophilic vitamins A, D and
      K, vitamin E is instead a pro-vitamin, with its quinone/hydroquinone metabolites
      responsible for its anti-ferroptotic cytoprotective activity.

PMID- 30110366
TI  - Nursing home admission after myocardial infarction in the elderly: A nationwide
      cohort study.
AB  - BACKGROUND: Data on nursing home admission after myocardial infarction (MI) in
      the elderly are scarce. We investigated nursing home admission within 6 months
      and 2 years after MI including predictors for nursing home admission in a
      nationwide cohort of elderly patients. METHODS: Using Danish nationwide
      registries, we identified all subjects 65 years or older residing at home who
      were discharged following first-time MI in the period 2008-2015. We determined
      sex- and age-stratified incidence rates per 1000 person years (IRs) and incidence
      rate ratios (IRRs) of nursing home admissions using Poisson regression models
      compared to the Danish population 65 years or older with no prior MI. Poisson
      regression models were also applied to identify predictors of nursing home
      admission. RESULTS: The 26,539 patients who were discharged after MI had a median
      age of 76 (quartile 1-quartile 3: 70-83) years. The IRs of nursing home admission
      after MI increased with increasing age and for 80-84-year-old women IRs after 6
      months and 2 years were 113.9 and 62.9, respectively, compared to 29.4 for women
      of the same age with no prior MI. The IRs for 80-84-year-old men after MI were
      56.0 and 36.2, respectively, compared to 24.3 for men of the same age with no
      prior MI. In adjusted analyses the 6 months and 2 years IRRs for 80-84-year-old
      subjects were 2.56 (95% CI 2.11-3.10) and 1.41 (95% CI 1.22-1.65) for women and
      1.74 (95% CI 1.34-2.25) and 1.05 (95% CI 0.88-1.26) for men, respectively.
      Predictors were advanced age, dementia, home care, Parkinson's disease,
      cerebrovascular disease, living alone, depression, and arrhythmia. CONCLUSION: In
      elderly patients discharged following first-time MI, the risk of subsequent
      nursing home admission within 6 months was 2-fold higher compared to an age
      stratified population with no prior MI. After 2 years this risk remained higher
      in women.

PMID- 30110367
TI  - Surveillance for respiratory syncytial virus and parainfluenza virus among
      patients hospitalized with pneumonia in Sarawak, Malaysia.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) and parainfluenza virus (PIV) are
      frequent causes of pneumonia and death among children at Sibu and Kapit Hospitals
      in Sarawak, Malaysia. OBJECTIVES: To determine the prevalence and risk factors
      for RSV subtypes A and B and PIV types 1-4 among patients hospitalized with
      pneumonia. METHODS: In a cross-sectional, pilot study nasopharyngeal swabs were
      studied with real-time reverse transcription polymerase chain reaction assays.
      Concurrently, we helped Sibu and Kapit Hospitals adapt their first molecular
      diagnostics for RSV and PIV. RESULTS: Of 129 specimens collected (June to July
      2017), 39 tested positive for RSV-A (30.2%), two were positive for RSV B (1.6%),
      one was positive for PIV-3 (0.8%) and one was positive for PIV-4 (0.8%). No
      samples were positive for PIV-1 or PIV-2. Of the 39 RSV-A positive specimens,
      46.2% were collected from children under one year of age and only 5.1% were from
      patients over the age of 18. A multivariable analysis found the odds of children
      <1 year of age testing positive for RSV-A were 32.7 (95% CI: 3.9, 276.2) times
      larger than >18 years of age, and the odds of patients hospitalized at Kapit
      Hospital testing positive for RSV-A were 3.2 (95% CI: 1.3, 7.8) times larger than
      patients hospitalized at Sibu Hospital. CONCLUSION: This study found an unusually
      high prevalence of RSV-A among pneumonia patients admitted to the two hospitals.
      Subsequently, Sibu Hospital adapted the molecular assays with the goal of
      providing more directed care for such pneumonia patients.

PMID- 30110368
TI  - Symptom severity and mindreading in narcissistic personality disorder.
AB  - BACKGROUND: Grandiose narcissism has been associated with poor ability to
      understand one's own mental states and the mental states of others. In
      particular, two manifestations of Narcissistic Personality Disorder (NPD) can be
      explained by poor mindreading abilities: absence of symptomatic subjective
      distress and lack of empathy. METHODS: We conducted two studies to investigate
      the relationships between mindreading capacity, symptomatic subjective distress
      and narcissistic personality. In the first study (N = 246), we compared
      mindreading capacities and symptomatic distress in three outpatient samples:
      narcissistic patients (NPD); patients with other Personality Disorders (PD);
      patients without PD. In the second study (N = 1357), we explored the
      relationships between symptomatic distress, mindreading and specific NPD
      criteria. RESULTS: In the first study, the NPD patients showed poorer mindreading
      than the patients without PD and comparable to patients with other PDs.
      Symptomatic subjective distress in the narcissistic group was less severe than in
      the other PDs group and comparable to the group without PDs. However, no
      relationship emerged between mindreading and symptomatic subjective distress. In
      the second study, taking the clinical sample as a whole, symptomatic distress
      appeared negatively linked to grandiosity traits, while mindreading scores were
      negatively linked to empathy. CONCLUSIONS: NPD showed specific mindreading
      impairments. However, mindreading capacity did not appear to be directly
      connected with subjective distress, but did appear to be connected with specific
      aspects of narcissistic pathology.

PMID- 30110369
TI  - Maternal and child characteristics and health practices affecting under-five
      mortality: A matched case control study in Gamo Gofa Zone, Southern Ethiopia.
AB  - BACKGROUND: Though Ethiopia has shown a considerable improvement in reducing
      under-five mortality rate since 1990, many children still continue to die
      prematurely. Mixed results have been reported about determinants of under-five
      mortality. Besides, there is paucity of mortality studies in the current study
      site. Therefore, this study was conducted to assess maternal and child health
      related predictors of under-five mortality in Southern Ethiopia. METHODS: A
      matched case control study was conducted in 2014 in Arba Minch Town and Arba
      Minch Zuria District of Gamo Gofa Zone, Southern Ethiopia. Conditional logistic
      regression was employed to identify the predictors of under-five mortality.
      Sampling weight was applied to account for the non-proportional allocation of
      sample to different clusters. Based on the Mosley & Chen's analytical framework
      for under-five and infant mortalities, the predictors were organized in to three
      groups: 1) personal illness control, 2) child feeding and newborn care and 3)
      other maternal and child related factors. RESULTS: Among personal illness control
      related factors: lack of post-natal care, immunization status of the child and
      lack of Vitamin A supplementation were significantly associated with higher rate
      of under-five mortality. Not breastfeeding and delaying first bath at least for
      24 hours were child feeding and newborn care related factors which were found to
      be significantly associated with under-five mortality. Among other maternal and
      child related factors, shorter previous birth interval, history of death of index
      child's older sibling, being multiple birth and live birth after the index child
      were significantly associated with under-five mortality. CONCLUSIONS: In order to
      maintain reduction of under-five mortality during the Sustainable Development
      Goals era, strengthening of maternal and child health interventions, such as post
      natal care, family planning, immunization, supplementation of Vitamin A for
      children older than six months, breastfeeding and delaying of first bath after
      delivery at least for 24 hours are recommended.

PMID- 30110372
TI  - Prediction of the caved rock zones' scope induced by caving mining method.
AB  - Critical medium column theory has typically been used to predict the scope of
      caved rock zone (CRZ) caused by caving mining method. It is essential to
      understand the distribution laws of lateral pressure induced by caving mining
      method with different dipping angles. In this study, a self-designed scaled
      physical model was used to investigate the distribution laws with angles ranging
      from 80 degrees  to 90 degrees , and ore drawing was employed in experiments to
      simulate caving mining method. The experimental results indicated that the
      distribution laws were divided into the reductive region and the extensive region
      during ore drawing. The reductive region was close to the drawing hole, and its
      scope was smaller than the other part. Moreover, decreasing the dipping angle was
      an effective way of controlling the maximum reduction rates and the scope of
      reductive region. By varying laws of lateral pressure, the predictive model of
      CRZs' scope was established. Additionally, the rock mass located outside the
      predictive CRZs' scope did not rupture based on the monitoring of Digital Optical
      Televiewing (OPTV), which was verified by the field test in Dabeishan Iron Mine,
      China. The results of the field test demonstrated that the prediction method used
      in this study was valid and could be used in practice.

PMID- 30110371
TI  - Poor statistical reporting, inadequate data presentation and spin persist despite
      editorial advice.
AB  - The Journal of Physiology and British Journal of Pharmacology jointly published
      an editorial series in 2011 to improve standards in statistical reporting and
      data analysis. It is not known whether reporting practices changed in response to
      the editorial advice. We conducted a cross-sectional analysis of reporting
      practices in a random sample of research papers published in these journals
      before (n = 202) and after (n = 199) publication of the editorial advice.
      Descriptive data are presented. There was no evidence that reporting practices
      improved following publication of the editorial advice. Overall, 76-84% of papers
      with written measures that summarized data variability used standard errors of
      the mean, and 90-96% of papers did not report exact p-values for primary analyses
      and post-hoc tests. 76-84% of papers that plotted measures to summarize data
      variability used standard errors of the mean, and only 2-4% of papers plotted raw
      data used to calculate variability. Of papers that reported p-values between 0.05
      and 0.1, 56-63% interpreted these as trends or statistically significant. Implied
      or gross spin was noted incidentally in papers before (n = 10) and after (n = 9)
      the editorial advice was published. Overall, poor statistical reporting,
      inadequate data presentation and spin were present before and after the editorial
      advice was published. While the scientific community continues to implement
      strategies for improving reporting practices, our results indicate stronger
      incentives or enforcements are needed.

PMID- 30110370
TI  - Zika might not be acting alone: Using an ecological study approach to investigate
      potential co-acting risk factors for an unusual pattern of microcephaly in
      Brazil.
AB  - Zika virus infections can cause a range of neurologic disorders including
      congenital microcephaly. However, while Zika infections have been notified across
      all regions in Brazil, there has been an unusual number of congenital
      microcephaly case notifications concentrated in the Northeast of the country. To
      address this observation, we investigated epidemiological data (2014-2016) on
      arbovirus co-distribution, environmental and socio-economic factors for each
      region in Brazil. Data on arbovirus reported cases and microcephaly were
      collected from several Brazilian Ministry of Health databases for each Federal
      unit. These were complemented by environmental management, social economic and
      Aedes aegypti infestation index data, extracted from multiple databases. Spatial
      time "ecological" analysis on the number of arboviruses transmitted by Aedes
      mosquitoes in Brazil show that the distribution of dengue and Zika was widespread
      in the whole country, with higher incidence in the West-Central region. However,
      reported chikungunya cases were higher in the Northeast, the region also with the
      highest number of microcephaly cases registered. Social economic factors (human
      development index and poverty index) and environmental management (water
      supply/storage and solid waste management) pointed the Northeast as the less
      wealthy region. The Northeast is also the region with the highest risk of Aedes
      aegypti house infestation due to the man-made larval habitats. In summary, the
      results of our ecological analysis support the hypothesis that the unusual
      distribution of microcephaly might not be due to Zika infection alone and could
      be accentuated by poverty and previous or co-infection with other pathogens. Our
      study reinforces the link between poverty and the risk of disease and the need to
      understand the effect on pathogenesis of sequential exposure to arboviruses and
      co-viral infections. Comprehensive large-scale cohort studies are required to
      corroborate our findings. We recommend that the list of infectious diseases
      screened, particularly during pregnancy, be regularly updated to include and
      effectively differentiate all viruses from ongoing outbreaks.

PMID- 30110373
TI  - Twenty-seven year surveillance of blood transfusion recipients infected with HIV
      1 in Hebei Province, China.
AB  - We conducted an investigation of blood management in which blood transfusion
      recipients underwent molecular biological analysis, to trace the possible source
      of HIV infection. Epidemiological investigation was carried out among HIV
      infected individuals. Blood transfusion recipients infected with HIV were tracked
      for the date of transfusion, reason for transfusion, hospital where transfusion
      was received, source of blood, components of transfusion, number of transfusions,
      and transfusion volume. A total of 285 blood transfusion recipients infected with
      HIV-1 were detected in Hebei over the study period, with 42.81% (122/285)
      detected through clinical diagnostic testing. These cases showed a concentrated
      distribution in southern Hebei, with local outbreak characteristics. A census of
      the population in Shahe County, which had a high concentration of cases, revealed
      that recipients of blood transfusions had an HIV infection rate of 15.54%
      (92/592). Post-transfusion infection frequently occurred among blood transfusion
      recipients at township medical institutions, with a peak in 1995. Owing to late
      detection of HIV infection among blood transfusion recipients, the rates of
      spousal transmission and mother-to-child transmission reached 20.87% and 28.05%,
      respectively. Around 1995, community medical institutions did not screen for HIV
      antibodies among paid blood donors, which was an important cause of the outbreak
      of HIV-1 infection among blood transfusion recipients. Our findings indicate that
      cases of blood transfusion-related infection decreased rapidly with gradual
      improvement in the HIV screening system for blood donors that began in 1995,
      particularly after full implementation of HIV nucleic acid testing of volunteer
      blood donors was begun in 2015.

PMID- 30110374
TI  - Effects of short-term in-season break detraining on repeated-sprint ability and
      intermittent endurance according to initial performance of soccer player.
AB  - To better understand the detraining effects in soccer, the purpose of the study
      was to analyse if performance level of soccer players modulate repeated-sprint
      ability (RSA) and intermittent endurance changes during 2-weeks of detraining
      (i.e., in-season break). Seventeen professional and sixteen young elite soccer
      players of two different teams performed, before and after 2-weeks of detraining,
      the RSA test and the Yo-Yo Intermittent Recovery Test, level 1 (YYIR1). Before
      detraining, professional players perform better (p < 0.05) RSA best time
      (RSAbest) than young players. A decrease (p < 0.05) in RSAbest, RSA total time
      (RSAtotal) and mean time (RSAmean) performance was observed in both teams,
      without changes in RSA fatigue index (Sdec). No significant changes in distance
      covered during YYIR1 was observed in any team. Before detraining, faster players
      from both teams (FG) (following the median split technique, soccer players with
      RSAbest <= 3.95 s) performed better (p < 0.01) in RSAtotal, RSAmean and RSAbest,
      but worse (p < 0.01) in Sdec. Although FG and the slower players (SG, RSAbest >
      3.95 s) showed a worse (p < 0.05) RSAtotal, RSAbest and RSAmean performance after
      detraining (ES = 1.5, 1.4 and 2.9; ES = 0.6, 1.2 and 0.6; for FG and SG,
      respectively), the deterioration was greater in the FG for RSAbest (p < 0.05) and
      RSAtotal (ES = 1.46). After detraining, FG improved (p < 0.05) Sdec performance.
      In conclusion, a 2-week in-season break (detraining) period induced a worse RSA,
      with no effect on intermittent endurance in professional and elite young soccer
      players, with greater detrimental effects on RSAtotal and RSAbest in FG. In
      addition, Sdec does not seem to be sensitive to changes in RSA after a 2-week in
      season break.

PMID- 30110375
TI  - A strong wink between verbal and emoji-based irony: How the brain processes
      ironic emojis during language comprehension.
AB  - Emojis are ideograms that are becoming ubiquitous in digital communication.
      However, no research has yet investigated how humans process semantic and
      pragmatic content of emojis in real time. We investigated neural responses to
      irony-producing emojis, the question being whether emoji-generated irony is
      processed similarly to word-generated irony. Previous ERP studies have routinely
      found P600 effects to verbal irony. Our research sought to identify whether the
      same neural responses could also be elicited by emoji-induced irony. In three
      experiments, participants read sentences that ended in either a congruent,
      incongruent, or ironic (wink) emoji. Results across all three experiments
      demonstrated clear P600 effects, the amplitudes of which were correlated with
      participants' tendency to treat the emoji as a marker of irony, as indicated by
      behavioral comprehension question responses. These ironic wink emojis also
      elicited a strong P200 effect, also found in studies of verbal irony processing.
      Moreover, unexpected emojis (both mismatch and ironic emoji) also elicited late
      frontal positivities, which have been implicated processing unpredicted words in
      context. These results are the first to identify how linguistically-relevant
      ideograms are processed in real-time at the neural level, and specifically draw
      parallels between the processing of word- and emoji-induced irony.

PMID- 30110376
TI  - The role of agriculture in women's nutrition: Empirical evidence from India.
AB  - In this paper, we establish a statistically important relationship between
      household agricultural income and women's BMI using a five-year panel dataset of
      rural households drawn from 18 villages across five Indian states. Using within
      household variation over time, we estimate both the extent to which short-term
      changes in agricultural income are associated with short-term changes in BMI, and
      the effect of agricultural income growth on BMI growth over a longer term. Over
      the longer term, and for the group of households that regularly farm, we find a
      10 percentage point agricultural income growth to be associated with a 0.10
      percentage point growth in BMI. Consistent with the literature, this effect is
      economically modest, but important considering that we do not find a
      corresponding effect for growth in non-agricultural income. We show that both the
      own-production and market purchase of food are associated with nutritional
      improvements. While women's BMI is associated with an increase in the consumption
      of own-produced cereals, the market plays an important role in facilitating
      access to more nutritious foods like pulses. Lastly, we also find that effects of
      agricultural income are driven by younger women, in the age-group 15-25 years,
      who face a particularly strong nutritional disadvantage in India.

PMID- 30110377
TI  - Estimating the cost of diagnosing HIV at birth in Lesotho.
AB  - BACKGROUND: Infants with HIV infection, particularly those infected in utero, who
      do not receive antiretroviral therapy (ART) have high mortality in the first year
      of life. Virologic diagnostic testing is recommended by the World Health
      Organization between ages 4 and 6 weeks after birth. However, adding very early
      infant diagnosis (VEID) testing at birth has been suggested to enable earlier
      diagnosis and rapid treatment of in utero infection. We assessed the costs of
      adding VEID to the standard 6-week testing in Lesotho where coverage of PMTCT
      services is nearly universal. METHODS: Retrospective cost data were collected at
      eight health-care facilities in three districts participating in an observational
      prospective study that included birth testing as well as at the National
      Reference Laboratory in Lesotho, to investigate the cost-per-infection
      identified. Extrapolating to the national level, it was possible to estimate the
      impact of VEID on the identification of HIV-infected infants. RESULTS: The unit
      cost-per-VEID test in Lesotho in 2015 was $40.50. Major cost drivers were
      supplies/commodities (46%) and clinical labor (22%). In 2015, 66.3% of cohort
      study infants born at study facilities underwent VEID; one out of 199 infants had
      a positive HIV DNA PCR test at birth (0.5% potential in utero infection),
      yielding a cost of $8,060 per HIV-positive infant identified. Sensitivity
      analysis showed costs based on Lesotho costing data ranged from $810 to $16,194
      per-infected child with varying in utero infection rates from 5% and 0.25%,
      respectively. With 11,157 HIV-exposed births nationally from pregnant women on
      PMTCT, 66.3% VEID coverage, and 0.5% in utero infection, 37 infants infected with
      HIV could have been identified at birth in 2015 and 8 early infant deaths
      potentially averted with immediate ART compared with waiting for 6-week testing.
      CONCLUSION: If Lesotho costing data from this pilot study were applied to
      different epidemic circumstances, the cost-per-infected child identified by
      adding VEID birth testing to standard 6-week testing was lowest when in utero
      infection rates were high (when HIV prevalence is high and PMTCT coverage is
      low).

PMID- 30110379
TI  - Correction: Clinicians' views of factors influencing decision-making for
      caesarean section: A systematic review and metasynthesis of qualitative,
      quantitative and mixed methods studies.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0200941.].

PMID- 30110378
TI  - Two-hour post-challenge hyperglycemia, but not fasting plasma glucose, associated
      with severity of coronary artery disease in patients with angina.
AB  - INTRODUCTION: Postprandial hyperglycemia plays a pivotal role in cardiovascular
      disease. However, few studies have investigated associations between the severity
      of coronary artery disease (CAD) and postprandial glucose levels in angina
      patients without known diabetes before coronary angiography. METHODS: Subjects
      who were admitted for coronary angiography due to angina and were in stable
      condition after discharge were recruited. A standard 75-g oral glucose tolerance
      test (OGTT) was performed at outpatient visits approximately 2-4 weeks after
      hospital discharge, and fasting and post-challenge blood glucose were measured.
      Twenty-six volunteers in our hospital staff served as the healthy group. CAD
      severity was graded using the SYNTAX and Jeopardy scoring systems. RESULTS: The
      subjects in the angina group had a higher body mass index, higher fasting
      glucose, and higher 2-h postprandial glucose than those in the healthy group. The
      SYNTAX and Jeopardy scores were significantly associated with 2-h postprandial
      blood glucose (correlation coefficients = 0.164 and 0.187, respectively) but not
      with fasting glucose. Linear regression analyses revealed that SYNTAX and
      Jeopardy scores were independently associated with glucose levels at 120 min
      after OGTT (SYNTAX 95%CI = 0.003-0.103; Jeopardy score 0.002-0.027) but not with
      fasting glucose. CONCLUSION: CAD severity is associated with blood glucose levels
      after oral glucose challenge in patients without known diabetes before coronary
      angiography, suggesting that CAD patients should be routinely screened for post
      challenge blood glucose.

PMID- 30110380
TI  - Multiple birth rates of Korea and fetal/neonatal/infant mortality in multiple
      gestation.
AB  - OBJECTIVE: This study was conducted to analyze recent trends of multiple birth
      rates (MBR) and fetal/neonatal/infant mortalities according to the number of
      gestations in Korea. METHODS: Data from 2009 to 2015 of live births, infant
      deaths and stillbirths were obtained from the Korean Vital Statistics. Neonatal
      mortality rate (NMR), infant mortality rate (IMR), and fetal mortality rate (FMR)
      in singleton, twin and triplet pregnancies were analyzed according to gestational
      period (GP; <= 23, 24-27, 28-31, and 32-36 weeks). RESULTS: From 2009 to 2015,
      twin and triplet birth rates increased 34.5% and 154.3%, respectively. In twin
      births, NMR and FMR have been decreased significantly (from 10.92 to 8.62, p =
      0.034 and from 41.00 to 30.55, p< 0.001, respectively), but IMR did not show
      significant decrease. There was no significant change of NMR, IMR, and FMR, in
      triplet births. Overall, in singleton, twin, and triplet births, NMR was 1.26 +/-
      0.09, 10.6 +/- 1.12, and 34.32 +/- 11.72, respectively, and IMR was 2.38 +/-
      0.26, 14.52 +/- 1.38, and 41.13 +/- 12.2, respectively. FMRs were 12 +/- 1.73,
      35.99 +/- 3.55, and 88.85 +/- 16.55, respectively, in singleton, twin, and
      triplet pregnancies. In spite of decreasing trends in overall mortalities, the
      odds ratios of NMRs and IMRs in 2015 were approximately 9-fold and 6-fold higher,
      respectively, in twin births, and approximately 37-fold and 20-fold higher,
      respectively, in triplet births, than those in singleton births. There were no
      significant differences in odds ratios of NMRs and IMRs at GP 32-36 among single,
      twin, and triplet births, although the odds ratios of FMR at GP 32-36 in triplet
      gestation was significantly higher than those in singleton and twin gestation.
      CONCLUSION: Neonatal/infant mortality in multiple births is still significantly
      high, which is mainly related with preterm birth. Close fetal monitoring is
      needed to prevent fetal death in triplet pregnancies, after 32 gestational weeks.

PMID- 30110381
TI  - Ruminal methane emissions, metabolic, and microbial profile of Holstein steers
      fed forage and concentrate, separately or as a total mixed ration.
AB  - Few studies have examined the effects of feeding total mixed ration (TMR) versus
      roughage and concentrate separately (SF) on ruminant methane production.
      Therefore, this study compared differences in methane production, ruminal
      characteristics, total tract digestibility of nutrients, and rumen microbiome
      between the two feeding methods in Holstein steers. A total six Holstein steers
      of initial bodyweights 540 +/- 34 kg were divided into two groups and assigned to
      a same experimental diet with two different feeding systems (TMR or SF) in a
      crossover design with 21 d periods. The experimental diet contained 73%
      concentrate and 27% forage and were fed twice a day. The total tract
      digestibility of crude protein, neutral detergent fibre, and organic matter were
      not affected by the two different feeding systems. Steers fed TMR emitted more
      methane (138.5 vs. 118.2 L/d; P < 0.05) and lost more gross energy as methane
      energy (4.0 vs. 3.5% gross energy intake; P = 0.005) compared to those fed SF.
      Steers fed TMR had greater (P < 0.05) total volatile fatty acid (VFA), ammonia-N
      concentrations and propionate proportion of total VFA at 1.5 h, whereas lower
      after that compared to steers fed SF. The greater (P < 0.05) acetate: propionate
      ratio at 4.5 h for steers fed TMR reflected the shift of H2 sink from propionate
      towards acetate synthesis. The lower (P < 0.05) isobutyrate and isovalerate
      proportions of total VFA observed in steers fed TMR implies decrease in net
      consumption of H2 for microbial protein synthesis compared to SF. There were no
      differences in both major bacterial and archaeal diversity between TMR and SF,
      unlike several minor bacterial abundances. The minor groups such as Coprococcus,
      Succiniclasticum, Butyrivibrio, and Succinivibrio were associated with the
      changes in ruminal VFA profiles or methanogenesis indirectly. Overall, these
      results indicate that SF reduces methane emissions from ruminants and increases
      propionate proportion of total VFA without affecting total tract digestion
      compared to TMR. There were no evidences that the response differed due to
      different major underlying microbial population.

PMID- 30110383
TI  - Moral growth mindset is associated with change in voluntary service engagement.
AB  - Incremental implicit theories are associated with a belief regarding it is
      possible to improve one's intelligence or ability through efforts. Previous
      studies have demonstrated that incremental implicit theories contributed to
      better academic achievement and positive youth development. Our study aimed to
      examine whether incremental implicit theories of morality significantly
      influenced change in students' engagement in voluntary service activities. In our
      study, 54 Korean college students for Study 1 and 180 Korean 8th graders for
      Study 2 were recruited to conduct two two-wave studies. We surveyed participants'
      implicit theories of morality and participation in voluntary service activities.
      The effect of implicit theories of morality on change in service engagement was
      analyzed through regression analysis. In Study 1, the moral growth mindset
      significantly moderated longitudinal change in service engagement. In Study 2,
      the moral growth mindset significantly influenced engagement in art-related
      activities, while it significantly moderated change in engagement in youth
      related activities.

PMID- 30110382
TI  - Multivariate analysis of genomics data to identify potential pleiotropic genes
      for type 2 diabetes, obesity and dyslipidemia using Meta-CCA and gene-based
      approach.
AB  - Previous studies have demonstrated the genetic correlations between type 2
      diabetes, obesity and dyslipidemia, and indicated that many genes have
      pleiotropic effects on them. However, these pleiotropic genes have not been well
      defined. It is essential to identify pleiotropic genes using systematic
      approaches because systematically analyzing correlated traits is an effective way
      to enhance their statistical power. To identify potential pleiotropic genes for
      these three disorders, we performed a systematic analysis by incorporating GWAS
      (genome-wide associated study) datasets of six correlated traits related to type
      2 diabetes, obesity and dyslipidemia using Meta-CCA (meta-analysis using
      canonical correlation analysis). Meta-CCA is an emerging method to systematically
      identify potential pleiotropic genes using GWAS summary statistics of multiple
      correlated traits. 2,720 genes were identified as significant genes after
      multiple testing (Bonferroni corrected p value < 0.05). Further, to refine the
      identified genes, we tested their relationship to the six correlated traits using
      VEGAS-2 (versatile gene-based association study-2). Only the genes significantly
      associated (Bonferroni corrected p value < 0.05) with more than one trait were
      kept. Finally, 25 genes (including two confirmed pleiotropic genes and eleven
      novel pleiotropic genes) were identified as potential pleiotropic genes. They
      were enriched in 5 pathways including the statin pathway and the PPAR (peroxisome
      proliferator-activated receptor) Alpha pathway. In summary, our study identified
      potential pleiotropic genes and pathways of type 2 diabetes, obesity and
      dyslipidemia, which may shed light on the common biological etiology and
      pathogenesis of these three disorders and provide promising insights for new
      therapies.

PMID- 30110384
TI  - Depressive and socially anxious symptoms, psychosocial maturity, and risk
      perception: Associations with risk-taking behaviour.
AB  - Risk-taking behaviour and onset of mental illness peak in adolescence and young
      adulthood. This study evaluated the interconnectedness of the domains of risk
      taking behaviour, mental health (symptoms of depression and social anxiety),
      psychosocial maturity, risk perception, age, and gender in a sample of 306
      adolescents and young adults. Participants between the ages of 16 and 35
      completed online self-report measures assessing risk-taking behaviour, depressive
      symptoms, socially anxious symptoms, psychosocial maturity and risk perception.
      Socially anxious symptoms, psychosocial maturity, and risk perception were
      directly associated with risk-taking behaviour. Correlations between depressive
      symptoms, socially anxious symptoms, and psychosocial maturity were found.
      Psychosocial maturity proved a better predictor of risk-taking behaviour than age
      in this cohort. The findings indicate that mental health impacts upon risk-taking
      behaviour and that consideration should be given to psychosocial maturity in
      attempts to reduce adolescent and young adult risk-taking behaviour.

PMID- 30110385
TI  - Reproducibility of isokinetic strength assessment of knee muscle actions in adult
      athletes: Torques and antagonist-agonist ratios derived at the same angle
      position.
AB  - The current study aimed to examine the reliability of the conventional and
      functional ratios derived from peak torques (PTs) and those obtained from the
      combination of knee flexors torque at the angle of knee extensors PT. Twenty-six
      male athletes (mean of 24.0+/-0.7 years) from different sports completed a test
      to-test variation in isokinetic strength (Biodex, System 3) within a period of
      one week. Anthropometry and body composition assessed by Dual Energy X-ray
      Absorptiometry were also measured. The proposed isokinetic strength ratio
      measurements appeared to be highly reliable: conventional ratio at PT angle
      (intra-class correlation, ICC = 0.98; 95% confidence interval; 95%CI: 0.95 to
      0.99); functional extension ratio at PT angle (ICC = 0.98; 95%CI: 0.96 to 0.99);
      and, functional flexion ratio at PT angle (ICC = 0.95; 95%CI: 0.89 to 0.98).
      Technical error of measurement (TEM) and associated percentage of the coefficient
      of variation (%CV) were as follows: conventional ratio at PT angle (TEM = 0.02;
      %CV = 4.1); functional extension ratio at PT angle (TEM = 0.02; %CV = 3.8); and,
      functional flexion ratio at PT angle (TEM = 0.03; %CV = 3.6). The current study
      demonstrated that the traditional and new obtained simple and combined isokinetic
      indicators seem highly reliable to assess muscle strength and function in adult
      male athletes. A single testing session seems to be sufficiently to obtain these
      isokinetic strength indicators.

PMID- 30110386
TI  - Topographical study of the trapezius muscle, greater occipital nerve, and
      occipital artery for facilitating blockade of the greater occipital nerve.
AB  - The aim of this study was to clarify the topographical relationships between the
      greater occipital nerve and the trapezius muscle and between the greater
      occipital nerve and the occipital artery in the occiput in order to increase the
      success rate of greater occipital nerve blockade. Fifty-six halved heads of 28
      cadavers were used in this study. The piercing points and the courses of the
      greater occipital nerve and occipital artery were analyzed by dividing a line
      connecting between the external occipital protuberance and mastoid process into
      three equal parts. A circle with a radius of 2 cm drawn at the medial trisection
      point of this line was divided into four equal sectors. The greater occipital
      nerve simply passed the lateral border of the trapezius muscle and then pierced
      the fascia connecting the cranial attachment of the trapezius muscle with the
      sternocleidomastoid muscle in 62.5% of the specimens, whereas it pierced the
      muscle itself in the other 37.5%. The greater occipital nerve and occipital
      artery pierced the fascia within the 2-cm-radius circle in 85.7% and 98.2% of the
      specimens, respectively. The piercing points of the greater occipital nerve and
      occipital artery were observed most frequently in the inferomedial (42.9%) and
      inferolateral (37.5%) sectors of the circle, respectively. The greater occipital
      nerve and occipital artery pierced the same sector of the circle and accompanied
      each other in 51.8% of the specimens. These results are expected to improve the
      understanding of the topographical relationships between the greater occipital
      nerve and trapezius muscle and between the greater occipital nerve and occipital
      artery in the occiput, and thus provide helpful information for the management of
      occipital neuralgia.

PMID- 30110387
TI  - Population structure, relatedness and ploidy levels in an apple gene bank
      revealed through genotyping-by-sequencing.
AB  - In recent years, new genome-wide marker systems have provided highly informative
      alternatives to low density marker systems for evaluating plant populations. To
      date, most apple germplasm collections have been genotyped using low-density
      markers such as simple sequence repeats (SSRs), whereas only a few have been
      explored using high-density genome-wide marker information. We explored the
      genetic diversity of the Pometum gene bank collection (University of Copenhagen,
      Denmark) of 349 apple accessions using over 15,000 genome-wide single nucleotide
      polymorphisms (SNPs) and 15 SSR markers, in order to compare the strength of the
      two approaches for describing population structure. We found that 119 accessions
      shared a putative clonal relationship with at least one other accession in the
      collection, resulting in the identification of 272 (78%) unique accessions. Of
      these unique accessions, over half (52%) share a first-degree relationship with
      at least one other accession. There is therefore a high degree of clonal and
      family relatedness in the Danish apple gene bank. We find significant genetic
      differentiation between Malus domestica and its supposed primary wild ancestor,
      M. sieversii, as well as between accessions of Danish origin and all others.
      Using the GBS approach allowed us to estimate ploidy levels, which were in
      accordance with flow cytometry results. Overall, we found strong concordance
      between analyses based on the genome-wide SNPs and the 15 SSR loci. However, we
      argue that GBS is superior to traditional SSR approaches because it allows
      detection of a much more detailed population structure and can be further
      exploited in genome-wide association studies (GWAS). Finally, we compare GBS with
      SSR for the purpose of identifying clones and pedigree relations in a diverse
      apple gene bank and discuss the advantages and constraints of the two approaches.

PMID- 30110388
TI  - Continuous nicotine exposure does not affect resurgence of alcohol seeking in
      rats.
AB  - Alcohol is the most commonly used drug in the United States and alcohol abuse can
      lead to alcohol use disorder. Alcohol use disorder is a persistent condition and
      relapse rates following successful remission are high. Many factors have been
      associated with relapse for alcohol use disorder, but identification of these
      factors has not been well translated into preventative utility. One potentially
      important factor, concurrent nicotine use, has not been well investigated as a
      causal factor in relapse for alcohol use disorder. Nicotine increases the value
      of other stimuli in the environment and may increase the value of alcohol. If
      nicotine increases the value of alcohol, then nicotine use during and after
      treatment may make relapse more probable. In the current study, we investigated
      the effect of continuous nicotine exposure (using osmotic minipumps to deliver
      nicotine or saline, depending on group, at a constant rate for 28 days) on
      resurgence of alcohol seeking in rats. Resurgence is a type of relapse
      preparation that consists of three phases: Baseline, Alternative Reinforcement,
      and Resurgence Testing. During Baseline, target responses produced a dipper of
      alcohol. During Alternative Reinforcement, target responses were extinguished and
      responses on a chain produced a chocolate pellet. During Resurgence Testing,
      responses on the chain were also extinguished and a return to responding on the
      target lever was indicative of resurgence. Multilevel modeling was used to
      analyze the effect of nicotine on resurgence. Both the nicotine and saline group
      showed resurgence of alcohol seeking, but there was no difference in the degree
      of resurgence across groups. Future directions could involve testing alternative
      drug delivery techniques.

PMID- 30110390
TI  - Retraction: Chaperonin CCT-Mediated AIB1 Folding Promotes the Growth of ERalpha
      Positive Breast Cancer Cells on Hard Substrates.

PMID- 30110389
TI  - To be funny or not to be funny: Gender differences in student perceptions of
      instructor humor in college science courses.
AB  - For over 50 years instructor humor has been recognized as a way to positively
      impact student cognitive and affective learning. However, no study has explored
      humor exclusively in the context of college science courses, which have the
      reputation of being difficult and boring. The majority of studies that explore
      humor have assumed that students perceive instructor humor to be funny, yet
      students likely perceive some instructor humor as unfunny or offensive. Further,
      evidence suggests that women perceive certain subjects to be more offensive than
      men, yet we do not know what impact this may have on the experience of women in
      the classroom. To address these gaps in the literature, we surveyed students
      across 25 different college science courses about their perceptions of instructor
      humor in college science classes, which yielded 1637 student responses. Open
      coding methods were used to analyze student responses to a question about why
      students appreciate humor. Multinomial regression was used to identify whether
      there are gender differences in the extent to which funny, unfunny, and offensive
      humor influenced student attention to course content, instructor relatability,
      and student sense of belonging. Logistic regression was used to examine gender
      differences in what subjects students find funny and offensive when joked about
      by college science instructors. Nearly 99% of students reported that they
      appreciate instructor humor and reported that it positively changes the classroom
      atmosphere, improves student experiences during class, and enhances the student
      instructor relationship. We found that funny humor tends to increase student
      attention to course content, instructor relatability, and student sense of
      belonging. Conversely, offensive humor tends to decrease instructor relatability
      and student sense of belonging. Lastly, we identified subjects that males were
      more likely to find funny and females were more likely to find offensive if a
      college science instructor were to joke about them.

PMID- 30110391
TI  - Wolbachia and host germline components compete for kinesin-mediated transport to
      the posterior pole of the Drosophila oocyte.
AB  - Widespread success of the intracellular bacterium Wolbachia across insects and
      nematodes is due to efficient vertical transmission and reproductive
      manipulations. Many strains, including wMel from Drosophila melanogaster, exhibit
      a specific concentration to the germplasm at the posterior pole of the mature
      oocyte, thereby ensuring high fidelity of parent-offspring transmission.
      Transport of Wolbachia to the pole relies on microtubules and the plus-end
      directed motor kinesin heavy chain (KHC). However, the mechanisms mediating
      Wolbachia's association with KHC remain unknown. Here we show that reduced levels
      of the host canonical linker protein KLC results in dramatically increased levels
      of Wolbachia at the oocyte's posterior, suggesting that KLC and some key
      associated host cargos outcompete Wolbachia for association with a limited amount
      of KHC motor proteins. Consistent with this interpretation, over-expression of
      KHC causes similarly increased levels of posteriorly localized Wolbachia.
      However, excess KHC has no effect on levels of Vasa, a germplasm component that
      also requires KHC for posterior localization. Thus, Wolbachia transport is
      uniquely KHC-limited because these bacteria are likely outcompeted for binding to
      KHC by some host cargo/linker complexes. These results reveal a novel host
      symbiont interaction that underscores the precise regulation required for an
      intracellular bacterium to co-opt, but not disrupt, vital host processes.

PMID- 30110392
TI  - Dialysis physicians' referral behaviors for hemodialysis patients suspected of
      having cancer: A vignette-based questionnaire study.
AB  - BACKGROUND: Although cancer management in dialysis patients has become a commonly
      encountered issue, known as "onco-nephrology", few evidence-based clinical
      recommendations have been proposed. Here, we examined the variation in referral
      behaviors adopted by dialysis physicians on encountering dialysis patients with
      signs/symptoms suggestive of cancer. METHODS: We conducted a vignette-based study
      in August 2015. We sent a 14-page questionnaire to 191 dialysis physicians,
      including the representative dialysis facilities participating in a Japanese
      dialysis cohort (the Japan Dialysis Outcomes and Practice Patterns Study). Using
      vignette scenarios for respiratory, digestive, and urological areas, we assessed
      the referral behaviors (expert referral or not) adopted by dialysis physicians on
      encountering dialysis patients with symptoms suggestive of cancer. Each scenario
      contained three patient functional factors: age (60 or 75 years), performance
      status (PS 0 or 1), and cognitive dysfunction (absence or presence). We examined
      the association between physician factors, patient factors, and referral
      behaviors. RESULTS: We obtained 94 replies (response rate: 49.2%). For the
      respiratory scenarios, 38.3% and 51.9% of physicians reported watchful waiting
      when encountering bilateral and unilateral pleural effusion, respectively. In
      digestive and urologic scenarios, most physicians (>85%) selected expert
      referral. We detected differences in referral behaviors between scenarios with
      different cancer biological factors. However, we found consistency in referral
      behaviors within the same scenario, even with different patient functional
      factors (intra-class correlation coefficients within each scenario all >0.7).
      CONCLUSIONS: Physicians' referral behaviors for dialysis patients suspected of
      having cancer vary for different cancer biological factors (probability of having
      cancer). However, the referral behaviors are similar for different patient
      functional factors (age, PS, and cognitive dysfunction).

PMID- 30110393
TI  - Correction: Pioneer farming in southeast Europe during the early sixth millennium
      BC: Climate-related adaptations in the exploitation of plants and animals.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0197225.].

PMID- 30110396
TI  - Nuclear magnetic resonance spectroscopy and infrared spectroscopy analysis of
      precipitate formed after mixing sodium hypochlorite and QMix 2in1.
AB  - BACKGROUND: Mixing sodium hypochlorite (NaOCl) with chlorhexidine (CHX) forms a
      brown precipitate. QMix-2in1 (QMix) was introduced as a final irrigant.
      Manufacturer recommends interim flushing with saline between the application of
      NaOCl and QMix to prevent formation of precipitation. This study assessed whether
      para-chloroaniline (PCA) is formed after mixing NaOCl with QMix. METHODS:
      Commercially available, 5.25% NaOCl solution, 2% CHX, QMix, 15%
      ethylenediaminetetraacetic acid (EDTA) and 98% PCA in powder form were used.
      Groups were prepared at room temperature. Group 1, 98% PCA in powder form; Group
      2, 2% chlorhexidine (CHX); Group 3, QMix; Group 4, 5.25% sodium hypochlorite
      (NaOCl) mixed with QMix; Group 5, 5.25% NaOCl mixed with CHX; Group 6, 15% EDTA
      mixed with CHX. The precipitates were extracted and analysed with Proton Nuclear
      Magnetic Resonance (1H-NMR) and Infrared (IR) Spectroscopy, using PCA as an
      internal standard. RESULTS: No PCA was found in any of the irrigant-mixture
      groups tested. CONCLUSIONS: This study used the interpretation of spectral
      results for the amino signals of precipitate formed after mixing QMix with 5.25%
      NaOCl using different nondestructive analysis methods, with PCA as an internal
      standard (control). We conclude that mixing QMix or 2%CHX with 5.25% NaOCl does
      not yield free PCA.

PMID- 30110394
TI  - Characterization of biochemical properties of an apurinic/apyrimidinic
      endonuclease from Helicobacter pylori.
AB  - Apurinic/apyrimidinic (AP) endonucleases play critical roles in the repair of
      abasic sites and strand breaks in DNA. Complete genome sequences of Helicobacter
      pylori reveal that this bacterial specie has a single AP endonuclease. An H.
      pylori homolog of Xth (HpXth) is a member of exonuclease III family, which is
      represented by Escherichia coli Xth. Currently, it remains unknown whether this
      single AP endonuclease has DNA repair activities similar to those of its
      counterpart in E. coli and other bacteria. We report that HpXth possesses
      efficient AP site cleavage, 3'-repair phosphodiesterase, and 3'-phosphatase
      activities but not the nucleotide incision repair function. Optimal reaction
      conditions for HpXth's AP endonuclease activity are low ionic strength, high Mg2+
      concentration, pH in the range 7-8, and temperature 30  degrees C. The kinetic
      parameters measured under steady-state conditions showed that HpXth removes the
      AP site, 3'-blocking sugar-phosphate, and 3'-terminal phosphate in DNA strand
      breaks with good efficiency (kcat/KM = 1240, 44, and 5,4 MUM-1.min-1,
      respectively), similar to that of E. coli Xth. As expected, the presence of HpXth
      protein in AP endonuclease-deficient E. coli xth nfo strain significantly reduced
      the sensitivity to an alkylating agent and H2O2. Mutation of active site residue
      D144 in HpXth predicted to be essential for catalysis resulted in a complete loss
      of enzyme activities. Several important structural features of HpXth were
      uncovered by homology modeling and phylogenetic analysis. Our data show the DNA
      substrate specificity of H. pylori AP endonuclease and suggest that HpXth
      counteracts the genotoxic effects of DNA damage generated by endogenous and host
      imposed factors.

PMID- 30110395
TI  - Association between cagA negative Helicobacter pylori status and nonalcoholic
      fatty liver disease among adults in the United States.
AB  - We investigated the relationship of H. pylori stratified by cytotoxin-associated
      gene A (cagA) status with nonalcoholic fatty liver disease (NAFLD) in the general
      population of the United States (US). We utilized the Third National Health and
      Nutrition Examination Survey from 1988 to 1994 in this study. NAFLD was defined
      by ultrasonographic detection of hepatic steatosis in the absence of other known
      causes of liver diseases and significant alcohol consumption. Hepatic steatosis
      was assessed by parenchymal brightness, liver to kidney contrast, deep beam
      attenuation, bright vessel walls and gallbladder wall definition. Antibodies to
      H. pylori and cagA of participants were measured using H. pylori IgG and anti
      cagA IgG enzyme-linked immunosorbent assays. Among 5,404 participants, the
      prevalence of NAFLD was higher in H. pylori positive subjects (33.5+/-1.8%)
      compared to H. pylori negative subjects (26.1+/-1.7%, p <0.001). In terms of cagA
      protein status stratification, while cagA positive H. pylori group did not
      demonstrate an association with NAFLD (OR: 1.05; 95% CI: 0.81-1.37), cagA
      negative H. pylori group was noted to have a significant association with NAFLD
      in a multivariable analysis (OR: 1.30; 95% CI: 1.01-1.67). In conclusion, our
      study demonstrated that cagA negative H. pylori infection was an independent
      predictor of NAFLD in the US general population.

PMID- 30110397
TI  - Compositionality in the language of emotion.
AB  - Emotions are signaled by complex arrays of face and body actions. The main point
      of contention in contemporary treatments is whether these arrays are discrete,
      holistic constellations reflecting emotion categories, or whether they are
      compositional-comprised of smaller components, each of which contributes some
      aspect of emotion to the complex whole. We address this question by investigating
      spontaneous face and body displays of athletes and place it in the wider context
      of human communicative signals and, in particular, of language. A defining
      property of human language is compositionality-the ability to combine and
      recombine a relatively small number of elements to create a vast number of
      complex meaningful expressions, and to interpret them. We ask whether this
      property of language can be discerned in a more ancient communicative system:
      intense emotional displays. In an experiment, participants interpreted a range of
      emotions and their strengths in pictures of athletes who had just won or lost a
      competition. By matching participants' judgements with minutely coded features of
      face and body, we find evidence for compositionality. The distribution of
      participants' responses indicates that most of the athletes' face and body
      features contribute to displays of dominance or submission. More particular
      emotional components related, for example, to positive valence (e.g. happy) or
      goal obstruction (e.g. frustrated), were also found to significantly correlate
      with certain face and body features. We propose that the combination of features
      linked to broader components (i.e, dominant or submissive) and to more particular
      emotions (e.g, happy or frustrated) reflects more complex emotional states. In
      sum, we find that the corporeal expression of intense, unfiltered emotion has
      compositional properties, potentially providing an ancient scaffolding upon
      which, millions of years later, the abstract and constrained compositional system
      of human language could build.

PMID- 30110398
TI  - Correction: A phase I study of niclosamide in combination with enzalutamide in
      men with castration-resistant prostate cancer.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198389.].

PMID- 30110399
TI  - Conservation genetics of two threatened frogs from the Mambilla highlands,
      Nigeria.
AB  - Amphibians are the vertebrate group with the highest number of species threatened
      with extinction, and habitat loss and fragmentation are considered to be among
      the leading causes of their declines and extinctions. Little is known of the
      population biology of amphibian species inhabiting montane forests in Central and
      West Africa, where anthropogenic activities such as farming and cattle raising
      are major threats to native biodiversity. We used Amplified Fragment Length
      Polymorphisms (AFLPs) to assess the population genetic structure of two poorly
      known species, Cardioglossa schioetzi and Leptodactylodon bicolor (both in the
      Arthroleptidae), in and around Ngel Nyaki Forest Reserve on the Mambilla Plateau
      in eastern Nigeria. The landscape comprises continuous forest on steep slopes and
      small riparian forest fragments in a grassland matrix. While increased
      fragmentation is well documented for these and other forests in the mountains of
      Cameroon and Nigeria over the past century, there are no previous assessments of
      the impact of forest fragmentation on montane amphibian populations in this
      region. Our estimates of genetic diversity are similar across populations within
      each species with levels of heterozygosity values consistent with local
      population declines. Except for a pair of populations (C. schioetzi) we did not
      observe genetic differentiation between forest and riparian forest fragment
      populations, nor across sites within continuous forest (L. bicolor). Our results
      demonstrate recent gene flow between forest fragments and the adjacent protected
      forests and suggest that small forest corridors connecting these may lessen the
      genetic consequences of at least 30 years of intense and severe fragmentation in
      Ngel Nyaki.

PMID- 30110400
TI  - Detection of pathogenic bacteria in the blood from sepsis patients using 16S rRNA
      gene amplicon sequencing analysis.
AB  - Prompt identification of causative pathogenic bacteria is imperative for the
      treatment of patients suffering from infectious diseases, including sepsis and
      pneumonia. However, current culture-based methodologies have several drawbacks
      including their limitation of use to culturable bacterial species. To circumvent
      these problems, we attempted to detect bacterial DNA in blood using next
      generation DNA sequencing (NGS) technology. We conducted metagenomic and 16S
      ribosomal RNA (rRNA) gene amplicon sequencing of DNA extracted from bacteria
      spiked blood using an Ion Personal Genome Machine. NGS data was analyzed using
      our in-house pipeline Genome Search Toolkit and database GenomeSync. The
      metagenomic sequencing analysis successfully detected three gram-positive and
      three gram-negative bacteria spiked in the blood, which was associated with a
      significant portion of non-bacterial reads, even though human blood cells were
      separated by low-speed centrifugation prior to DNA extraction. Sequencing
      analysis of seven variable regions of the 16S rRNA gene amplicon also
      successfully detected all six bacteria spiked in the blood. The methodology using
      16S rRNA gene amplicon analysis was verified using DNA from the blood of six
      patients with sepsis and four healthy volunteers with potential pathogenic
      bacteria in the blood being identified at the species level. These findings
      suggest that our system will be a potential platform for practical diagnosis in
      the future.

PMID- 30110402
TI  - Cerium promoted V-g-C3N4 as highly efficient heterogeneous catalysts for the
      direct benzene hydroxylation.
AB  - A series of Ce x -V-g-C3N4 catalysts with different cerium content were
      synthesized by a facile co-assembly method. Compared with pure V-g-C3N4 catalyst,
      the addition of cerium facilitated the high dispersion of vanadium species as
      well as the benzene adsorption ability of the corresponding catalysts. Also, the
      existence of cerium promoted the partial reduction of vanadium species, which
      improved the redox property of vanadium species as the active centres. The Ce x 
      V-g-C3N4 catalysts showed considerably improved activity in the benzene
      hydroxylation reaction compared with V-g-C3N4 catalyst. Among the catalysts
      studied, Ce0.07-0.07 V-g-C3N4 exhibited the best catalytic activity with a
      benzene conversion of 33.7% and a phenol yield of 32.3% with good structural and
      catalytic stability, while only 24.7% of benzene conversion and phenol yield of
      24.2% were obtained over 0.07 V-g-C3N4.

PMID- 30110401
TI  - Tramadol-induced hepato- and nephrotoxicity in rats: Role of Curcumin and Gallic
      acid as antioxidants.
AB  - Tramadol is an analgesic used to treat moderate to severe pain caused by cancer,
      osteoarthritis, and other musculoskeletal diseases. Cytochrome P450 system
      metabolizes tramadol and induces oxidative stress in different organs. Therefore,
      the present study aims at investigating the changes in the activities and the
      protein expressions of CYPs isozymes (2E1, 3A4, 2B1/2), antioxidants status, free
      radicals levels after pretreatment of rats with Curcumin and/or Gallic as single-
      and/or repeated-doses before administration of tramadol. In repeated-dose
      treatments of rats with tramadol, the activities of cytochrome P450, cytochrome
      b5, and NADPH-cytochrome-c-reductase, and the antioxidant enzymes including
      glutathione reductase, glutathione peroxidase, glutathione S-transferase,
      catalase, superoxide dismutase, and levels of glutathione were inhibited in the
      liver and the kidney of rats. Interestingly, such changes caused by tramadol
      restored to their normal levels after pretreatment of rats with either Curcumin
      and/or Gallic acid. On the other hand, repeated-dose treatment of rats with
      tramadol increased the activities of both dimethylnitrosamine N-demethylase I
      (DMN-dI), and aryl hydrocarbon hydroxylase (AHH) compared to the control group.
      However, pretreatment of rats with Curcumin and/or Gallic acid prior to
      administration of tramadol restored the inhibited DMN-dI activity and its protein
      expression (CYP 2E1) to their normal levels. On the other hand, tramadol
      inhibited the activity of ethoxycoumarin O-deethylase (ECOD) and suppressed its
      protein marker expression (CYP2B1/2), whereas Curcumin, Gallic acid and/or their
      mixture restored such changes to their normal levels. In conclusion, Curcumin
      and/or Gallic acid alleviated the adverse effects caused by tramadol. In
      addition, patients should be advice to take Curcumin and/or Gallic acid prior to
      tramadol treatment to alleviate the hepatic and renal toxicities caused by
      tramadol.

PMID- 30110404
TI  - Material composition of the mouthpart cuticle in a damselfly larva (Insecta:
      Odonata) and its biomechanical significance.
AB  - Odonata larvae are key predators in their habitats. They catch prey with a unique
      and highly efficient apparatus, the prehensile mask. The mandibles and maxillae,
      however, play the lead in handling and crushing the food. The material
      composition of the cuticle in the biomechanical system of the larval mouthparts
      has not been studied so far. We used confocal laser scanning microscopy (CLSM) to
      detect material gradients in the cuticle by differences in autofluorescence. Our
      results show variations of materials in different areas of the mouthparts: (i)
      resilin-dominated pads within the membranous transition between the labrum and
      the anteclypeus, which support mobility and might provide shock absorption, an
      adaptation against mechanical damage; (ii) high degrees of sclerotization in the
      incisivi of the mandibles, where high forces occur when crushing the prey's body
      wall. The interaction of the cuticle geometry, the material composition and the
      related musculature determine the complex concerted movements of the mouthparts.
      The material composition influences the strength, mobility and durability of the
      cuticular components of the mouthparts. Applying CLSM for extracting information
      about material composition and material properties of arthropod cuticles will
      considerably help improve finite-element modelling studies.

PMID- 30110403
TI  - Fast formation of a supramolecular ion gel/solvoplastic elastomer with excellent
      stretchability.
AB  - This study describes a simple yet efficient approach for the preparation of an
      ionic gel that is also elastomeric in its solid-state bulk form. A series of
      poly(2-(diethylamino)ethyl methacrylate-co-lauryl methacrylate) P(DMAEMA-co-LMA)
      copolymers were synthesized first by radical polymerization. Quaternization of
      the PDMAEMA component in tetrahydrofuran enables the formation of supramolecular
      network, giving rise to an ion gel. An elastomer with an elongation at break of
      over 600% was obtained from the gel. The elastomer, connected by supramolecular
      ionic cross-links, is solvoplastic in certain solvents. The simple yet efficient
      approach of the formation of ion-gel and the dried elastomer allows fast
      preparation of both gel-like and solid-state elastic materials for various
      applications where recyclability is required.

PMID- 30110405
TI  - Base-catalysed decomposition of polychlorinated biphenyls in transformer oils by
      mixture of sodium hydroxide, glycerol and iron.
AB  - In this research, a method based on base-catalysed decomposition (BCD) was
      developed using sodium hydroxide and glycerol for dechlorination of transformer
      oils with low levels of polychlorinated biphenyls (PCBs). PCB removal and
      dechlorination efficiencies were measured by gas chromatography and the silver
      nitrate titration method, respectively. PCB dechlorination and removal
      efficiencies after 4 h at 250 degrees C and in the presence of iron were 97.4%
      and 99.8%, respectively. However, in the absence of iron the same efficiencies
      were calculated to be 79.4 and 99.7%, respectively. The dielectric loss factor of
      oil refined at 250 degrees C was 0.0064 and did not meet the required standards
      to be reused in the transformers. However, that refined at 200 degrees C
      satisfied the standards with acceptable conversion rates. Use of iron, besides
      increasing conversion rates, changed the mechanism of the reaction from
      nucleophilic substitution to a combination of hydrodechlorination and
      nucleophilic substitution. In the presence of iron, highly chlorinated PCBs were
      converted to less chlorinated PCBs, and this caused the concentration of less
      chlorinated PCBs to reach a peak and then decline thereafter. The production of
      PCB 36 confirmed this. However, in the absence of iron particles, all changes in
      the PCB concentration curves were downward.

PMID- 30110406
TI  - Mice modulate ultrasonic calling bouts according to sociosexual context.
AB  - Mice produce various sounds within the ultrasonic range in social contexts.
      Although these sounds are often used as an index of sociability in biomedical
      research, their biological significance remains poorly understood. We previously
      showed that mice repeatedly produced calls in a sequence (i.e. calling bout),
      which can vary in their structure, such as Simple, Complex or Harmonics. In this
      study, we investigated the use of the three types of calling bouts in different
      sociosexual interactions, including both same- and opposite-sex contexts. In same
      sex contexts, males typically produced a Simple calling bout, whereas females
      mostly produced a Complex one. By contrast, in the opposite-sex context, they
      produced all the three types of calling bouts, but the use of each calling type
      varied according to the progress and mode of sociosexual interaction (e.g.
      Harmonic calling bout was specifically produced during reproductive behaviour).
      These results indicate that mice change the structure of calling bout according
      to sociosexual contexts, suggesting the presence of multiple functional signals
      in their ultrasonic communication.

PMID- 30110407
TI  - The mono(catecholamine) derivatives as iron chelators: synthesis, solution
      thermodynamic stability and antioxidant properties research.
AB  - There is a growing interest in the development of new iron chelators as novel
      promising therapeutic strategies for neurodegenerative disorders. In this
      article, a series of mono(catecholamine) derivatives, 2,3-bis(hydroxy)-N
      (hydroxyacyl)benzamide, containing a pendant hydroxy, have been synthesized and
      fully characterized by nuclear magnetic resonance, Fourier transform infrared
      spectroscopy and mass spectrum. The thermodynamic stability of the chelators with
      FeIII, MgII and ZnII ions was then investigated. The chelators enable formation
      of (3 : 1) FeIII complexes with high thermodynamic stability and exhibited
      improved selectivity to FeIII ion. Meanwhile, the results of 1,1-diphenyl-2
      picryl-hydrazyl assays of mono(catecholamine) derivatives indicated that they all
      possess excellent antioxidant properties. These results support the hypothesis
      that the mono(catecholamine) derivatives be used as high-affinity chelator for
      iron overload situations without depleting essential metal ions, such as MgII and
      ZnII ions.

PMID- 30110408
TI  - The behaviour of overweight dogs shows similarity with personality traits of
      overweight humans.
AB  - Excessive food intake and the resulting excess weight gain is a growing problem
      in human and canine populations. Dogs, due to their shared living environment
      with humans, may provide a beneficial model to study the causes and consequences
      of obesity. Here, we make use of two well-established research paradigms (two-way
      choice paradigm and cognitive bias test), previously applied with dogs, to
      investigate the role of obesity and obesity-prone breeds for food responsiveness.
      We found no evidence of breed differences in food responsiveness due to one breed
      being more prone to obesity than another. Breed differences found in this study,
      however, can be explained by working dog status, i.e. whether the dog works in
      cooperation with, or independently from, humans. Our results also confirm that
      overweight dogs, as opposed to normal weight dogs, tried to maximize food intake
      from the higher quality food and hesitated to do the task when the food reward
      was uncertain. These results are very similar to those expected from the parallel
      models that exist between certain personality traits and being overweight in
      humans, suggesting that dogs are indeed a promising model for experimentally
      investigating obesity in humans.

PMID- 30110409
TI  - Intramolecular hydrogen bonds in 1,4-dihydropyridine derivatives.
AB  - 1,4-Dihydropyridine (1,4-DHP) derivatives have been synthesized and characterized
      by 1H, 13C, 15N nuclear magnetic resonance (NMR) spectroscopy, secondary
      proton/deuterium 13C isotope shifts, variable temperature 1H NMR experiments and
      quantum-chemical calculation. The intramolecular hydrogen bonds NH?O=C and CH?O=C
      in these compounds were established by NMR and quantum-chemical studies The
      downfield shift of the NH proton, accompanied by the upfield shift of the 15N
      nuclear magnetic resonance signals, the shift to the higher wavenumbers of the NH
      stretching vibration in the infrared spectra and the increase of the 1J(15N,1H)
      values may indicate the shortening of the N-H bond length upon intramolecular
      NH?O=C hydrogen bond formation.

PMID- 30110410
TI  - A multi-functional chemosensor for highly selective ratiometric fluorescent
      detection of silver(I) ion and dual turn-on fluorescent and colorimetric
      detection of sulfide.
AB  - A multi-functional chemosensor 1 as silver and sulfide detector was synthesized
      by the combination of octopamine and 4-dimethylaminocinnamaldehyde. Sensor 1
      exhibited a ratiometric fluorescence emission for Ag+ from blue to sky. The
      binding mode of 1 and Ag+ turned out to be a 1 : 1 ratio as determined using Job
      plot and electrospray ionization (ESI) mass spectral analyses. The sensing
      mechanism of 1 with silver ion was unravelled by 1H NMR titrations and
      theoretical calculations. Sensor 1 also discerned sulfide by enhancing
      fluorescence intensity and changing colour from yellow to colourless in aqueous
      solution. The sensing properties of 1 toward S2- were investigated by using ESI
      mass analysis, Job plot and 1H NMR titrations. Moreover, 1 could be used as a
      detector for sulfide in a wide pH range.

PMID- 30110411
TI  - The effect of thermo-oxidative ageing on crystallization, dynamic and static
      mechanical properties of long glass fibre-reinforced polyamide 10T composites.
AB  - The performances and microstructure of long glass fibre-reinforced polyamide 10T
      (PA10T/LGF) composites that experienced different ageing temperatures (160 and
      200 degrees C) with increasing ageing time are characterized by differential
      scanning calorimetry (DSC), mechanical analysis, thermogravimetric analysis (TGA)
      and scanning electron microscopy to probe the correlation between properties of
      the composites and thermo-oxidative ageing. The DSC results show that PA10T/LGF
      composites occur on degradation, the fracture of molecular chains and the
      destruction of crystallization structure, which leads to the crystallization and
      melting peaks of PA10T/LGF composites to shift to high temperature. On the basis
      of dynamic mechanical analysis data, the reduction of the interfacial bonding
      between the glass fibre and PA10T matrix and the motion of molecular chain
      segments result in the thermo-oxidative ageing of composites. According to the
      calculation of activation energy (E), thermo-oxidative temperature and ageing
      time can bring about the decline of the E value, proving the deterioration in
      performance of PA10T/LGF composites. In view of TGA, the increase in the thermo
      oxidative temperature and ageing time promotes the degradation of PA10T/LGF
      composites. The tensile, flexural and notched impact strengths of PA10T/LGF
      composites decline with prolonging the ageing temperature and time. The surface
      of materials produces some microcracks and the cross-section surface of PA10T/LGF
      composites becomes rougher.

PMID- 30110412
TI  - Synthesis and characterization of Zr- and Hf-doped nano-TiO2 as internal
      standards for analytical quantification of nanomaterials in complex matrices.
AB  - The reliable quantification of nanomaterials (NMs) in complex matrices such as
      food, cosmetics and biological and environmental compartments can be challenging
      due to interactions with matrix components and analytical equipment (vials and
      tubing). The resulting losses along the analytical process (sampling, extraction,
      clean-up, separation and detection) hamper the quantification of the target NMs
      in these matrices as well as the compatibility of results and meaningful
      interpretations in safety assessments. These issues can be overcome by the
      addition of known amounts of internal/recovery standards to the sample prior to
      analysis. These standards need to replicate the behaviour of target analytes in
      the analytical process, which is mainly defined by the surface properties.
      Moreover, they need to carry a tag that can be quantified independently of the
      target analyte. As inductively coupled plasma mass spectrometry is used for the
      identification and quantification of NMs, doping with isotopes, target analytes
      or with chemically related rare elements is a promising approach. We present the
      synthesis of a library of TiO2 NMs doped with hafnium (Hf) and zirconium (Zr)
      (both low in environmental abundance). Zirconia NMs doped with Hf were also
      synthesized to complement the library. NMs were synthesized with morphological
      and size properties similar to commercially available TiO2. Characterization
      included: transmission electron microscopy coupled with energy-dispersive X-ray
      spectroscopy, X-ray diffraction spectroscopy, Brunauer-Emmett-Teller total
      specific surface area analysis, cryofixation scanning electron microscopy,
      inductively coupled plasma optical emission spectroscopy and UV-visible
      spectrometry. The Ti : Hf and Ti : Zr ratios were verified and calculated using
      Rietveld refinement. The labelled NMs can serve as internal standards to track
      the extraction efficiency from complex matrices, and increase method robustness
      and traceability of characterization/quantification.

PMID- 30110413
TI  - Analysis of the regulation networks in grapevine reveals response to waterlogging
      stress and candidate gene-marker selection for damage severity.
AB  - Owing to the climate change impacts, waterlogging is one of the most hazardous
      abiotic stresses to crops, which also can result in a serious reduction in the
      quantity and quality of grape berry and wine production during the rainy season.
      Therefore, the exploration of the response mechanism of grape to waterlogging is
      necessary, for which the analysis of the transcriptomic regulation networks of
      grapevine leaves in response to waterlogging stress was carried out. In this
      study, 12 634 genes were detected in both waterlogging stress and control
      grapevine plants, out of which 6837 genes were differentially expressed. A
      comparative analysis revealed that genes functioning in the antioxidant system,
      glycolysis and fermentation pathway, chlorophyll metabolism, amino acid
      metabolism and hormones were activated to reduce injury to grapes under the
      waterlogging stress. Meanwhile, genes encoding class-2 non-symbiotic haemoglobin
      were determined as important in waterlogging acclimation. Additionally, the
      expression variations of three marker genes were found to be informative and can
      be used to predict the viability of the grapevines subjected to waterlogging.
      This research not only probes the molecular mechanism underlying grapevine
      waterlogging tolerance but also puts forward an idea about the application of
      gene expression information to practical management.

PMID- 30110414
TI  - A new fossil marine lizard with soft tissues from the Late Cretaceous of southern
      Italy.
AB  - A new marine lizard showing exceptional soft tissue preservation was found in
      Late Cretaceous deposits of the Apulian Platform (Puglia, Italy). Primitivus
      manduriensis gen. et sp. nov. is not only the first evidence of the presence of
      dolichosaurs in a southern Italian Carbonate Platform, filling a palaeogeographic
      gap in the Mediterranean Tethys, but also extends the range of this group to the
      upper Campanian-lower Maastrichtian. Our parsimony analysis recovers a
      monophyletic non-ophidian pythonomorph clade, including Tetrapodophis amplectus
      at the stem of Mosasauroidea + Dolichosauridae, which together represent the
      sister group of Ophidia (modern and fossil snakes). Based on Bayesian inference
      instead, Pythonomorpha is monophyletic, with Ophidia representing the more deeply
      nested clade, and the new taxon as basal to all other pythonomorphs. Primitivus
      displays a fairly conservative morphology in terms of both axial elongation of
      the trunk and limb reduction, and the coexistence of aquatic adaptations with
      features hinting at the retention of the ability to move on land suggests a semi
      aquatic lifestyle. The exceptional preservation of mineralized muscles, portions
      of the integument, cartilages and gut content provides unique sources of
      information about this extinct group of lizards. The new specimen may represent
      local persistence of a relict dolichosaur population until almost the end of the
      Cretaceous in the Mediterranean Tethys, and demonstrates the incompleteness of
      our knowledge of dolichosaur temporal and spatial distributions.

PMID- 30110415
TI  - Phylogenomic history of enigmatic pygmy perches: implications for biogeography,
      taxonomy and conservation.
AB  - Pygmy perches (Percichthyidae) are a group of poorly dispersing freshwater fishes
      that have a puzzling biogeographic disjunction across southern Australia. Current
      understanding of pygmy perch phylogenetic relationships suggests past east-west
      migrations across a vast expanse of now arid habitat in central southern
      Australia, a region lacking contemporary rivers. Pygmy perches also represent a
      threatened group with confusing taxonomy and potentially cryptic species
      diversity. Here, we present the first study of the evolutionary history of pygmy
      perches based on genome-wide information. Data from 13 991 ddRAD loci and a
      concatenated sequence of 1 075 734 bp were generated for all currently described
      and potentially cryptic species. Phylogenetic relationships, biogeographic
      history and cryptic diversification were inferred using a framework that combines
      phylogenomics, species delimitation and estimation of divergence times. The
      genome-wide phylogeny clarified the biogeographic history of pygmy perches,
      demonstrating multiple east-west events of divergence within the group across the
      Australian continent. These results also resolved discordance between nuclear and
      mitochondrial data from a previous study. In addition, we propose three cryptic
      species within a southwestern species complex. The finding of potentially new
      species demonstrates that pygmy perches may be even more susceptible to
      ecological and demographic threats than previously thought. Our results have
      substantial implications for improving conservation legislation of pygmy perch
      lineages, especially in southwestern Western Australia.

PMID- 30110416
TI  - Thrifty phenotype versus cold adaptation: trade-offs in upper limb proportions of
      Himalayan populations of Nepal.
AB  - The multi-stress environment of high altitude has been associated with growth
      deficits in humans, particularly in zeugopod elements (forearm and lower leg).
      This is consistent with the thrifty phenotype hypothesis, which has been observed
      in Andeans, but has yet to be tested in other high-altitude populations. In
      Himalayan populations, other factors, such as cold stress, may shape limb
      proportions. The current study investigated whether relative upper limb
      proportions of Himalayan adults (n = 254) differ between highland and lowland
      populations, and whether cold adaptation or a thrifty phenotype mechanism may be
      acting here. Height, weight, humerus length, ulna length, hand length and hand
      width were measured using standard methods. Relative to height, total upper limb
      and ulna lengths were significantly shorter in highlanders compared with
      lowlanders in both sexes, while hand and humerus length were not. Hand width did
      not significantly differ between populations. These results support the thrifty
      phenotype hypothesis, as hand and humerus proportions are conserved at the
      expense of the ulna. The reduction in relative ulna length could be attributed to
      cold adaptation, but the lack of difference between populations in both hand
      length and width indicates that cold adaptation is not shaping hand proportions
      in this case.

PMID- 30110417
TI  - Making of a single solid-state nanopore on the wall of fused silica capillary.
AB  - A channel of nanometre size is an important platform for nanofluidic
      investigations. In this work, we show that a single solid nanopore can be
      generated by hydrogen fluoride etching of the outside wall of commercially
      available fused silica capillary. The geometry, size and the singleness were
      characterized by various means, including scanning electron microscope,
      electrolyte conductance measurement and a fluorescent microscope. The generation
      principle is also discussed. The nanopore thus generated features in low aspect
      ratio and exhibits typical nanofluidic effects such as ion concentration
      polarization, rectification and molecular translocation.

PMID- 30110418
TI  - Separate block-based parameter estimation method for Hammerstein systems.
AB  - Different from the output-input representation-based identification methods of
      two-block Hammerstein systems, this paper concerns a separate block-based
      parameter estimation method for each block of a two-block Hammerstein CARMA
      system, without combining the parameters of two parts together. The idea is to
      consider each block as a subsystem and to estimate the parameters of the
      nonlinear block and the linear block separately (interactively), by using two
      least-squares algorithms in one recursive step. The internal variable between the
      two blocks (the output of the nonlinear block, and also the input of the linear
      block) is replaced by different estimates: when estimating the parameters of the
      nonlinear part, the internal variable between the two blocks is computed by the
      linear function; when estimating the parameters of the linear part, the internal
      variable is computed by the nonlinear function. The proposed parameter estimation
      method possesses property of the higher computational efficiency compared with
      the previous over-parametrization method in which many redundant parameters need
      to be computed. The simulation results show the effectiveness of the proposed
      algorithm.

PMID- 30110420
TI  - Committing to quantum resistance: a slow defence for Bitcoin against a fast
      quantum computing attack.
AB  - Quantum computers are expected to have a dramatic impact on numerous fields due
      to their anticipated ability to solve classes of mathematical problems much more
      efficiently than their classical counterparts. This particularly applies to
      domains involving integer factorization and discrete logarithms, such as public
      key cryptography. In this paper, we consider the threats a quantum-capable
      adversary could impose on Bitcoin, which currently uses the Elliptic Curve
      Digital Signature Algorithm (ECDSA) to sign transactions. We then propose a
      simple but slow commit-delay-reveal protocol, which allows users to securely move
      their funds from old (non-quantum-resistant) outputs to those adhering to a
      quantum-resistant digital signature scheme. The transition protocol functions
      even if ECDSA has already been compromised. While our scheme requires
      modifications to the Bitcoin protocol, these can be implemented as a soft fork.

PMID- 30110419
TI  - Effects of dimming light-emitting diode street lights on light-opportunistic and
      light-averse bats in suburban habitats.
AB  - Emerging lighting technologies provide opportunities for reducing carbon
      footprints, and for biodiversity conservation. In addition to installing light
      emitting diode street lights, many local authorities are also dimming street
      lights. This might benefit light-averse bat species by creating dark refuges for
      these bats to forage and commute in human-dominated habitats. We conducted a
      field experiment to determine how light intensity affects the activity of the
      light-opportunistic Pipistrellus pipistrellus and light-averse bats in the genus
      Myotis. We used four lighting levels controlled under a central management system
      at existing street lights in a suburban environment (0, 25, 50 and 100% of the
      original output). Higher light intensities (50 and 100% of original output)
      increased the activity of light-opportunistic species but reduced the activity of
      light-averse bats. Compared to the unlit treatment, the 25% lighting level did
      not significantly affect either P. pipistrellus or Myotis spp. Our results
      suggest that it is possible to achieve a light intensity that provides both
      economic and ecological benefits by providing sufficient light for human
      requirements while not deterring light-averse bats.

PMID- 30110421
TI  - Effect of Hf-doping on electrochemical performance of anatase TiO2 as an anode
      material for lithium storage.
AB  - Hafnium-doped titania (Hf/Ti = 0.01; 0.03; 0.05) had been facilely synthesized
      via a template sol-gel method on carbon fibre. Physico-chemical properties of the
      as-synthesized materials were characterized by X-ray diffraction, Raman
      spectroscopy, scanning electron microscopy, energy-dispersive X-ray analysis,
      scanning transmission electron microscopy, X-ray photoelectron spectroscopy,
      thermogravimetry analysis and Brunauer-Emmett-Teller measurements. It was
      confirmed that Hf4+ substitute in the Ti4+ sites, forming Ti1-x Hf x O2 (x =
      0.01; 0.03; 0.05) solid solutions with an anatase crystal structure. The Ti1-x Hf
      x O2 materials are hollow microtubes (length of 10-100 um, outer diameter of 1-5
      um) composed of nanoparticles (average size of 15-20 nm) with a surface area of
      80-90 m2 g-1 and pore volume of 0.294-0.372 cm3 g-1. The effect of Hf ion
      incorporation on the electrochemical behaviour of anatase TiO2 in the Li-ion
      battery anode was investigated by galvanostatic charge/discharge and
      electrochemical impedance spectroscopy. It was established that Ti0.95Hf0.05O2
      shows significantly higher reversibility (154.2 mAh g-1) after 35-fold cycling at
      a C/10 rate in comparison with undoped titania (55.9 mAh g-1). The better
      performance offered by Hf4+ substitution of the Ti4+ into anatase TiO2 mainly
      results from a more open crystal structure, which has been achieved via the
      difference in ionic radius values of Ti4+ (0.604 A) and Hf4+ (0.71 A). The
      obtained results are in good accord with those for anatase TiO2 doped with Zr4+
      (0.72 A), published earlier. Furthermore, improved electrical conductivity of Hf
      doped anatase TiO2 materials owing to charge redistribution in the lattice and
      enhanced interfacial lithium storage owing to increased surface area directly
      depending on the Hf/Ti atomic ratio have a beneficial effect on electrochemical
      properties.

PMID- 30110422
TI  - Climate structuring of Batrachochytrium dendrobatidis infection in the threatened
      amphibians of the northern Western Ghats, India.
AB  - Batrachochytrium dendrobatidis (Bd) is a pathogen killing amphibians worldwide.
      Its impact across much of Asia is poorly characterized. This study systematically
      surveyed amphibians for Bd across rocky plateaus in the northern section of the
      Western Ghats biodiversity hotspot, India, including the first surveys of the
      plateaus in the coastal region. These ecosystems offer an epidemiological model
      system since they are characterized by differing levels of connectivity, edaphic
      and climatic conditions, and anthropogenic stressors. One hundred and eighteen
      individuals of 21 species of Anura and Apoda on 13 plateaus ranging from 67 to
      1179 m above sea level and 15.89 to 17.92 degrees  North latitude were sampled.
      Using qPCR protocols, 79% of species and 27% of individuals tested were positive
      for Bd. This is the first record of Bd in caecilians in India, the Critically
      Endangered Xanthophryne tigerina and Endangered Fejervarya cf. sahyadris. Mean
      site prevalence was 28.15%. Prevalence below the escarpment was 31.2% and 25.4%
      above. The intensity of infection (GE) showed the reverse pattern. Infection may
      be related to elevational temperature changes, thermal exclusion, inter-site
      connectivity and anthropogenic disturbance. Coastal plateaus may be thermal
      refuges from Bd. Infected amphibians represented a wide range of ecological
      traits posing interesting questions about transmission routes.

PMID- 30110423
TI  - Transition mechanism for a periodic bar-and-joint framework with limited degrees
      of freedom controlled by uniaxial load and internal stiffness.
AB  - A specific periodic bar-and-joint framework with limited degrees of freedom is
      shown to have a transition mechanism when subjected to an external force. The
      static nonlinear elasticity of this framework under a uniaxial load is modelled
      with the two angular variables specifying the rotation and distortion of the
      linked square components. Numerically exploring the equilibrium paths then
      reveals a transition state of the structure at a critical value of the internal
      stiffness. A simplified formulation of the model with weak nonlinear terms yields
      an exact solution of its transition state. Load-displacement behaviour and
      stability for the two systems with or without approximation are analysed and
      compared.

PMID- 30110424
TI  - High-performance single-walled carbon nanotube transparent conducting film
      fabricated by using low feeding rate of ethanol solution.
AB  - We report floating catalyst chemical vapour deposition synthesis of single-walled
      carbon nanotubes (SWCNTs) for high-performance transparent conducting films
      (TCFs) using low feeding rate of precursor solution. Herein, ethanol acts as
      carbon source, ferrocene and thiophene as catalyst precursor and growth promoter,
      respectively. By adopting a low feeding rate of 4 ul min-1, the fabricated TCFs
      present one of the lowest sheet resistances of ca 78 Omega sq.-1. at 90%
      transmittance. Optical characterizations demonstrate that the mean diameter of
      high-quality SWCNTs is up to 2 nm. Additionally, electron microcopy observations
      provide evidence that the mean length of SWCNT bundles is as long as 28.4 um
      while the mean bundle diameter is only 5.3 nm. Moreover, very few CNT loops can
      be found in the film. Remarkably, the fraction of individual SWCNTs reaches
      24.6%. All those morphology data account for the superior optoelectronic
      performance of our SWCNT TCFs.

PMID- 30110425
TI  - A lateral flow strip based on gold nanoparticles to detect 6-monoacetylmorphine
      in oral fluid.
AB  - We used lateral flow strips based on gold nanoparticles to detect 6
      monoacetylmorphine (6-MAM; heroin's unique metabolite) in oral fluid samples. In
      this competitive lateral chromatographic immunoassay, the 6-MAM was chemically
      synthesized and conjugated to bovine serum albumin. The results were
      qualitatively detected via the colour change of the test line. By using a proper
      sample pad, a suitable nitrocellulose membrane and a customized sponge device
      adsorbed the oral fluid directly from the mouth; the total test time was 3 min.
      The sensitivity of the assay was 4.0 ng ml-1 without any cross-reactivity with 10
      normal drugs, which are widely subject to abuse, including morphine and codeine.
      This test could be easily used on site to detect heroin in oral fluid, and it
      could be a promising product in the future including for driving under the
      influence.

PMID- 30110426
TI  - Solutions for the problems of silicon-carbon anode materials for lithium-ion
      batteries.
AB  - Lithium-ion batteries are widely used in various industries, such as portable
      electronic devices, mobile phones, new energy car batteries, etc., and show great
      potential for more demanding applications like electric vehicles. Among advanced
      anode materials applied to lithium-ion batteries, silicon-carbon anodes have been
      explored extensively due to their high capacity, good operation potential,
      environmental friendliness and high abundance. Silicon-carbon anodes have
      demonstrated great potential as an anode material for lithium-ion batteries
      because they have perfectly improved the problems that existed in silicon anodes,
      such as the particle pulverization, shedding and failures of electrochemical
      performance during lithiation and delithiation. However, there are still some
      problems, such as low first discharge efficiency, poor conductivity and poor
      cycling performance, which need to be improved. This paper mainly presents some
      methods for solving the existing problems of silicon-carbon anode materials
      through different perspectives.

PMID- 30110428
TI  - Individual performance in team-based online games.
AB  - Complex real-world challenges are often solved through teamwork. Of special
      interest are ad hoc teams assembled to complete some task. Many popular
      multiplayer online battle arena (MOBA) video-games adopt this team formation
      strategy and thus provide a natural environment to study ad hoc teams. Our work
      examines data from a popular MOBA game, League of Legends, to understand the
      evolution of individual performance within ad hoc teams. Our analysis of player
      performance in successive matches of a gaming session demonstrates that a
      player's success deteriorates over the course of the session, but this effect is
      mitigated by the player's experience. We also find no significant long-term
      improvement in the individual performance of most players. Modelling the short
      term performance dynamics allows us to accurately predict when players choose to
      continue to play or end the session. Our findings suggest possible directions for
      individualized incentives aimed at steering the player's behaviour and improving
      team performance.

PMID- 30110427
TI  - The high-level basis of body adaptation.
AB  - Prolonged visual exposure, or 'adaptation', to thin (wide) bodies causes a
      perceptual aftereffect such that subsequently seen bodies appear wider (thinner)
      than they actually are. Here, we conducted two experiments investigating the
      effect of rotating the orientation of the test stimuli by 90 degrees  from that
      of the adaptor. Aftereffects were maximal when adapting and test bodies had the
      same orientation. When they differed, the axis of the perceived distortion
      changed with the orientation of the body. Experiment 1 demonstrated a 58%
      transfer of the aftereffect across orientations. Experiment 2 demonstrated an
      even greater degree of aftereffect transfer when the influence of low-level
      mechanisms was reduced further by using adaptation and test stimuli with
      different sizes. These results indicate that the body aftereffect is mediated
      primarily by high-level object-based processes, with low-level retinotopic
      mechanisms playing only a minor role. The influence of these low-level processes
      is further reduced when test stimuli differ in size from adaptation stimuli.

PMID- 30110429
TI  - Optimized modelling and application of exhaust gas recirculation performance
      evaluation of turbocharged diesel engine.
AB  - Aimed at the problem of exhaust gas recirculation (EGR) performance evaluation
      and optimal EGR rate determination of turbocharged diesel engines, an optimized
      decision-making method, based on grey theory and entropy weight, was proposed.
      The internal combustion pressure, fuel consumption rate, NOX, CO and smoke were
      selected as the decision-making targets and the initial decision-making model was
      established based on the traditional grey decision-making theory. According to
      the characteristics and optimization requirements of EGR, the optimal compromise
      between combustion and emission performance is proposed to transform into
      decision-making target weighting problem, then an optimized subjective weighting
      method based on expert scoring and grey relational analysis is proposed. Finally,
      the entropy weight method was used to solve the objective weight and the
      optimized multi-objective grey decision-making model was established, which can
      not only weaken the human error of subjective empowerment, but also fully explore
      the intrinsic relationship of the evaluation indexes. At last, an optimization
      simulation platform for EGR performance evaluation based on MATLB/GUIDE was
      designed and established. The results show that the optimization simulation
      platform can effectively improve the efficiency of simulation calculation, which
      is more convenient for practical engineering applications. The optimized method
      can successfully realize EGR performance evaluation and optimal EGR rate
      determination under different working conditions. The decision-making result was
      consistent with the present EGR control strategies, which provide a new research
      idea for EGR performance optimization.

PMID- 30110430
TI  - The boundary of holistic processing in the appraisal of facial attractiveness.
AB  - Facial attractiveness is often studied on the basis of the internal facial
      features alone. This study investigated how this exclusion of the external
      features affects the perception of attractiveness. We studied the effects of two
      most commonly used methods of exclusion, where the shape of an occluding mask was
      defined by either the facial outline or an oval. Participants rated
      attractiveness of the same faces under these conditions. Results showed that
      faces were consistently rated more attractive when they were masked by an oval
      shape rather than by their outline (Experiment 1). Attractive faces were more
      strongly affected by this effect than were less attractive faces when
      participants were able to control the viewing time. However, unattractive faces
      benefited more from this effect when the same face stimuli were presented briefly
      for only 20 ms (Experiment 2). Further manipulation confirmed that the effect was
      mainly due to the occlusion of a larger area of the external features rather than
      the regular and symmetrical features of the oval shape (Experiment 3) or lacks
      contextual cues about the face boundary (Experiment 4). The effect was only
      relative to masked faces, with no advantage over unmasked faces (Experiment 5),
      and is likely a result of the interaction between the shape of a mask and the
      internal features of the face. This holistic effect in the appraisal of facial
      attractiveness is striking, because the oval shape of the mask is not a part of
      the face but is the edge of an occluding object.

PMID- 30110431
TI  - A periodic Markov model to formalize animal migration on a network.
AB  - Regular, long-distance migrations of thousands of animal species have
      consequences for the ecosystems that they visit, modifying trophic interactions
      and transporting many non-pathogenic and pathogenic organisms. The spatial
      structure and dynamic properties of animal migrations and population flyways
      largely determine those trophic and transport effects, but are yet poorly
      studied. As a basis, we propose a periodic Markov model on the spatial migration
      network of breeding, stopover and wintering sites to formally describe the
      process of animal migration on the population level. From seasonally changing
      transition rates we derived stable, seasonal densities of animals at the network
      nodes. We parametrized the model with high-quality GPS and satellite telemetry
      tracks of white storks (Ciconia ciconia) and greater white-fronted geese (Anser
      a. albifrons). Topological and network flow properties of the two derived
      networks conform to migration properties like seasonally changing connectivity
      and shared, directed movement. Thus, the model realistically describes the
      migration movement of complete populations and can become an important tool to
      study the effects of climate and habitat change and pathogen spread on migratory
      animals. Furthermore, the property of periodically changing transition rates
      makes it a new type of complex model and we need to understand its dynamic
      properties.

PMID- 30110432
TI  - Ratiometric fluorescent test paper based on silicon nanocrystals and carbon dots
      for sensitive determination of mercuric ions.
AB  - Classical dye absorption-based pH test papers are widely used to measure the
      degree of acidity of media for quantification or semi-quantification by the
      observation of the naked eye on the variation of colour. However, it remains a
      challenging task to extend portable and cheap methods to a wide range of analytes
      for accurate quantification. Here, we report a dosage-sensitive test paper for
      the assay of mercury ions (Hg2+) with wide colour evolution. The ratiometric
      fluorescent probe was prepared by mixing blue-emission silicon nanocrystals (Si
      NCs) and red-emission carbon dots (r-CDs). The Si NCs serve as the reaction site
      and the r-CDs as the internal reference. Upon the addition of Hg2+, the blue
      fluorescence of the Si NCs was quenched, while the red fluorescence of the r-CDs
      remained constant, resulting in the consecutive fluorescence colour changes from
      blue to orange red. The probe demonstrates high selectivity and sensitivity of
      the visualization assay of Hg2+ with a detection limit of 7.63 nM. Moreover, we
      printed the ratiometric fluorescence probe result onto a piece of filter paper to
      prepare a test paper, which represents an on-site, sensitive, rapid and cost
      effective method for the visual determination of Hg2+ by the naked eye.

PMID- 30110433
TI  - Effect of demonstrator reliability and recency of last demonstration on
      acquisition of a socially transmitted food preference.
AB  - In the social transmission of food preference paradigm, naive observer rats
      acquire safety information about novel food sources in the environment through
      social interaction with a demonstrator rat that has recently eaten said food.
      Research into the behavioural mechanisms governing this form of learning has
      found that observers show increased reliance on socially acquired information
      when the state of the environment makes personal examination of their
      surroundings risky. We aimed to (1) determine whether reliance on social
      information would decrease if previous reliance on social learning was
      unsuccessful, and (2) whether reliance on the specific demonstrator that had
      transmitted poor information would similarly decrease. By inducing illness in
      observers following consumption of a socially demonstrated food, we created an
      environmental situation in which reliance on socially acquired information was
      maladaptive. We found that under these conditions, observers showed no change in
      their reliance on a specific demonstrator or socially learned information in
      general. Our experiment also unexpectedly produced results showing that recent
      demonstrators were more influential in later transmissions than demonstrators
      that had been learned from less recently. Notably, this effect only emerged when
      the observer simultaneously interacted with both demonstrators, indicating that
      demonstrators must be in direct competition for this effect to manifest.

PMID- 30110434
TI  - Multi-scale investigation of the formation and properties of high-grade rutile
      TiO2 from titanium slags using microwave heating.
AB  - In this paper, the phase transition of titanium slag under microwave heating
      observed through electron microscopy was systematically investigated. The phase
      identification and transformation as well as the morphology of samples before and
      after each treatment were characterized using X-ray powder diffraction (XRD),
      Fourier-transform infrared spectroscopy, Raman spectroscopy and scanning electron
      microscopy (SEM). The XRD confirmed that sodium salt roasting could modify the
      phase composition of titanium slag. The microwave roasting in the presence of
      sodium salt increased the rutile TiO2 with high crystallinity after acid
      leaching. The Raman spectroscopy demonstrated the phase transition of titanium
      slag from anosovite to rutile TiO2 after a series of treatments, and the SEM
      analyses showed that the surface of calcined products grew plenty of rutile TiO2
      with typical characteristics. The results indicate a successful process for an
      effective and efficient way for the utilization of both titanium slag and
      preparation of rutile TiO2.

PMID- 30110435
TI  - Cracking the egg: the use of modern and fossil eggs for ecological, environmental
      and biological interpretation.
AB  - A myriad of extant and extinct vertebrates produce eggs. Eggs and eggshells
      provide a useful substrate for reconstructing environment, ecology and biology
      over a range of time scales from deep time to the present. In this review,
      methods for analysing and understanding records of diet, climate, environment and
      biology preserved in eggshells are presented. Topics covered include eggshell
      structure, assessing diagenesis, stable isotope geochemistry and morphological
      investigations of eggshell characteristics. This review emphasizes the use of
      eggshells in the modern and fossil record, as they allow for interpretation of
      characteristics of a wide variety of amniotes across geological history, uniquely
      informing environmental and ecological investigations.

PMID- 30110437
TI  - Thermal evolution of the crystal structure and phase transitions of KNbO3.
AB  - The thermal evolution of the crystal structure and phase transitions of KNbO3
      were investigated by high-temperature powder X-ray diffraction and Rietveld
      refinement of the diffraction data. Two phase transitions from orthorhombic
      (Amm2) to tetragonal (P4mm) and from tetragonal to cubic ( Pm3-m ) were
      confirmed, both on heating and cooling. Both phase transitions are first order
      based on the observed hysteresis. The mixed displacive and order-disorder nature
      of the tetragonal to cubic transition is argued based on symmetry and apparent
      divergence of the atomic positions from pseudo-cubic values. The transition
      between the orthorhombic and tetragonal phase shows no temperature-dependence for
      atomic positions and only thermal expansion of the unit cell parameters and is
      thus discussed in relation to a lattice dynamical instability.

PMID- 30110436
TI  - Molecular mechanism of viscoelastic polymer enhanced oil recovery in nanopores.
AB  - Polymer flooding is a promising chemical enhanced oil recovery (EOR) method,
      which realizes more efficient extraction in porous formations characterized with
      nanoscale porosity and complicated interfaces. Understanding the molecular
      mechanism of viscoelastic polymer EOR in nanopores is of great significance for
      the advancement of oil exploitation. Using molecular dynamics simulations, we
      investigated the detailed process of a viscoelastic polymer displacing oil at the
      atomic scale. We found that the interactions between polymer chains and oil
      provide an additional pulling effect on extracting the residual oil trapped in
      dead-end nanopores, which plays a key role in increasing the oil displacement
      efficiency. Our results also demonstrate that the oil displacement ability of
      polymer can be reinforced with the increasing chain length and viscoelasticity.
      In particular, a polymer with longer chain length exhibits stronger elastic
      property, which enhances the foregoing pulling effect. These findings can help to
      enrich our understanding on the molecular mechanism of polymer enhanced oil
      recovery and provide guidance for oil extraction engineering.

PMID- 30110438
TI  - Correlations between SIRT1 gene polymorphisms and diabetic kidney disease.
AB  - To investigate the correlations between SIRT1 gene polymorphisms and diabetic
      kidney disease (DKD). There were 150 patients with DKD in the observation group
      (urinary albumin excretion rate (UAER) >= 300 mg 24 h-1), and 160 patients with a
      more than 10 year history of type 2 diabetes but without retinopathy and DKD
      (UAER < 30 mg 24 h-1) in the control group. Genotypes of three tagged single
      nucleotide polymorphism loci (rs3818292, rs4746720 and rs10823108) in the SIRT1
      gene in the two groups were detected. Risks of DKD for patients with the GG and
      GG + AG genotype in the rs10823108 locus of the SIRT1 gene were 2.96 and 2.92
      times higher than that for AA genotype carriers, respectively. The risk of DKD
      for patients with the GG genotype in the rs3818292 locus was 0.23 times and 0.21
      times higher than that for AA and for AA + AG genotype carriers, respectively,
      and the risk of DKD for patients with allele G was 0.66 times higher than that
      for allele A carriers. There was no significant difference in genotype frequency
      of rs4746720 locus gene polymorphisms between the observation and control groups.
      The SIRT1 gene is a genetic susceptibility gene of DKD. Mutation genotype GG and
      GG + AG in the rs10823108 locus can increase the risk of DKD. Mutation genotype
      GG and allele G in the rs3818292 locus can decrease the risk of DKD.

PMID- 30110439
TI  - Forward and inverse problems in the mechanics of soft filaments.
AB  - Soft slender structures are ubiquitous in natural and artificial systems, in
      active and passive settings and across scales, from polymers and flagella, to
      snakes and space tethers. In this paper, we demonstrate the use of a simple and
      practical numerical implementation based on the Cosserat rod model to simulate
      the dynamics of filaments that can bend, twist, stretch and shear while
      interacting with complex environments via muscular activity, surface contact,
      friction and hydrodynamics. We validate our simulations by solving a number of
      forward problems involving the mechanics of passive filaments and comparing them
      with known analytical results, and extend them to study instabilities in
      stretched and twisted filaments that form solenoidal and plectonemic structures.
      We then study active filaments such as snakes and other slender organisms by
      solving inverse problems to identify optimal gaits for limbless locomotion on
      solid surfaces and in bulk liquids.

PMID- 30110440
TI  - Preparation of palladized carbon nanotubes encapsulated iron composites: highly
      efficient dechlorination for trichloroethylene and low corrosion of nanoiron.
AB  - A method developed based on the capillary effect and capillary condensation
      theory was used to synthesize an innovative Fe/C/Pd composite in this study. This
      composite (Fe@CNTs@Pd) consists of carbon nanotubes (CNTs) with nanoscale
      zerovalent iron (NZVI) on the inner surface and palladium nanoparticles supported
      on the outer surface of CNTs. This structure successfully addresses the problems
      of high iron corrosion rate and lower utilization rate of hydrogen in the
      application of bimetal nanoparticles for trichloroethylene (TCE) removal. TCE
      degradation experiments and electrochemical tests were conducted to investigate
      the material properties and reaction mechanisms of the composite. It is found
      that the prepared composite material contribute a high level of TCE
      dechlorination rate and substantially reduced hydrogen production during iron
      corrosion in water compared with the conventional CNTs-supported bimetal
      materials (Fe/Pd@CNTs). Hydrogen spillover effect helps the reactivity of
      Fe@CNTs@Pd for TCE degradation and suppressed the galvanic cell effect, which
      results in a stronger resistance to corrosion. Although the Kobs of Fe@CNTs@Pd
      was 16.87% lower than that of Fe/Pd@CNTs, the hydrogen production rate of
      Fe@CNTs@Pd was 10 times slower than that of Fe/Pd@CNTs. Therefore, Fe@CNTs@Pd
      shows a significant reduction in the corrosion rate at a cost of slightly slower
      degradation of TCE. In sum, the prepared composites demonstrate important
      characteristics, including alleviating NZVI agglomeration, maintaining high TCE
      removal efficiency and reducing the corrosion of NZVI.

PMID- 30110441
TI  - Missing the point: re-evaluating the earliest lithic technology in the Middle
      Orinoco.
AB  - The Culebra site, located in close proximity to the Atures Rapids, is one of the
      very few open-air occupations in the entire Orinoco valley that is thought to
      date to the early Holocene. Following renewed excavations in this location, we
      characterize the stone technology in unprecedented detail and perform both
      quantitative and qualitative analyses of the assemblage deposited in the first
      cultural layers. Additionally, we directly date the sediment forming the
      depositional context of the assemblage using stratigraphically stable components
      of soil organic matter. Coupled with our stratigraphic and paedological data, the
      deposit is, contrary to established estimates, shown to date to the late
      Holocene, well after the appearance of ceramics in the region. The toolkit
      identified through the lithic analysis, therefore, does not reflect an Archaic
      hunter-gatherer adaptation as previously assumed. Our findings are placed in the
      context of previous research in the Orinoco and lowland South America more
      broadly. More work is needed to understand the changing role of different stone
      tool reduction sequences with reference to adaptational strategies and
      bioclimatic variability.

PMID- 30110442
TI  - Computational modelling for decision-making: where, why, what, who and how.
AB  - In order to deal with an increasingly complex world, we need ever more
      sophisticated computational models that can help us make decisions wisely and
      understand the potential consequences of choices. But creating a model requires
      far more than just raw data and technical skills: it requires a close
      collaboration between model commissioners, developers, users and reviewers. Good
      modelling requires its users and commissioners to understand more about the whole
      process, including the different kinds of purpose a model can have and the
      different technical bases. This paper offers a guide to the process of
      commissioning, developing and deploying models across a wide range of domains
      from public policy to science and engineering. It provides two checklists to help
      potential modellers, commissioners and users ensure they have considered the most
      significant factors that will determine success. We conclude there is a need to
      reinforce modelling as a discipline, so that misconstruction is less likely; to
      increase understanding of modelling in all domains, so that the misuse of models
      is reduced; and to bring commissioners closer to modelling, so that the results
      are more useful.

PMID- 30110443
TI  - A phenomenological model for structural phase transitions in incommensurate
      alkane/urea inclusion compounds.
AB  - n-Alkane/urea inclusion compounds are crystalline materials in which n-alkane
      'guest' molecules are located within parallel one-dimensional 'host' tunnels
      formed by a helical hydrogen-bonded arrangement of urea molecules. The periodic
      repeat distance of the guest molecules along the host tunnels is incommensurate
      with the periodic repeat distance of the host substructure. The structural
      properties of the high-temperature phase of these materials (phase I), which
      exist at ambient temperature, are described by a (3 + 1)-dimensional superspace.
      Recent publications have suggested that, in the prototypical incommensurate
      composite systems, n-nonadecane/urea and n-hexadecane/urea, two low-temperature
      phases II and 'III' exist and that one or both of these phases are described by a
      (3 + 2)-dimensional superspace. We present a phenomenological model based on
      symmetry considerations and developed in the frame of a pseudo-spin-phonon
      coupling mechanism, which accounts for the mechanisms responsible for the I <->
      II <-> 'III' phase sequence. With reference to published experimental data, we
      demonstrate that, in all phases of these incommensurate materials, the structural
      properties are described by (3 + 1)-dimensional superspace groups. Around the
      temperature of the II <-> 'III' transition, the macroscopic properties of the
      material are not actually associated with a phase transition, but instead
      represent a 'crossover' between two regimes involving different couplings between
      relevant order parameters.

PMID- 30110444
TI  - Evaluation of polybenzimidazole-based polymers for the removal of uranium,
      thorium and palladium from aqueous medium.
AB  - Four types of polybenzimidazole (PBI)-based polymers (m-PBI, p-PBI, pyridine
      based m-PBI and alkylated m-PBI) have been prepared and characterized. Extraction
      behaviour of heavy metal ions, viz. U(VI), Th(IV) and Pd(II), with these polymers
      was investigated. Distribution ratios for the extraction of these metal ions were
      measured as a function of nitric acid concentration. Extraction data reveal that,
      in general, p-PBI exhibits a higher distribution ratio for U(VI), Th(IV) and
      Pd(II) compared with the other polymeric resins evaluated in the present study.
      Column chromatography experiments were carried out with a solution of U(VI),
      Th(IV) and Pd(II) in dilute nitric acid media using columns packed with m- and p
      PBI polymeric material for understanding the sorption and elution behaviour. The
      p-PBI-based resin has shown higher palladium sorption capacity (1.8 mmol g-1).
      The studies also established that p-PBI resin is a potential candidate material
      for the recovery of U(VI) and Th(IV) (capacity 0.22 mmol g-1 and 0.13 mmol g-1)
      from an aqueous stream, e.g. mine water samples.

PMID- 30110445
TI  - Synthesis and molecular docking studies of some novel Schiff bases incorporating
      6-butylquinolinedione moiety as potential topoisomerase IIbeta inhibitors.
AB  - A series of novel pyranoquinolinone-based Schiff's bases were designed and
      synthesized. They were evaluated for topoisomerase IIbeta (TOP2B) inhibitory
      activity, and cytotoxicity against breast cancer cell line (MCF-7) for the
      development of novel anticancer agents. A molecular docking study was employed to
      investigate their binding and functional properties as TOP2B inhibitors, using
      the Discovery Studio 2.5 software, where they showed very interesting ability to
      intercalate the DNA-topoisomerase complex. Compounds 2a, 2c and 2f showed high
      docking score values (82.36% -29.98 kcal mol-1 for compound 2a, 78.18% -26.98
      kcal mol-1 for compound 2c and 78.65, -28.11 kcal mol-1 for compound 2f) and
      revealed the highest enzyme inhibition activity. The best hit compounds exhibited
      highly potent TOP2B inhibitors with submicromolar IC50 at 5 uM compared to the
      reference doxorubicin.

PMID- 30110446
TI  - The effect of static versus dynamic stimuli on visual processing of sexual cues
      in androphilic women and gynephilic men.
AB  - Models of sexual response posit that attentional processing of sexual cues is
      requisite for sexual responding. Despite hypothesized similarities in the
      underlying processes resulting in sexual response, gender differences in sexual
      arousal patterns are abundant. One such gender difference relates to the stimulus
      features (e.g. gender cues, sexual activity cues) that elicit a response in men
      and women. In this study, we examined how stimulus modality (static visual images
      versus dynamic audiovisual films) and stimulus features (gender, sexual activity
      and nonsexual contextual cues) influences attentional (i.e. gaze) and elaborative
      (i.e. self-reported attraction (SRA), self-reported arousal) processing of sexual
      stimuli. Men's initial and controlled attention was consistently gender-specific
      (i.e. greater attention towards female targets), and this was not influenced by
      stimulus modality or the presence of sexual activity cues. By contrast, gender
      specificity of women's attention patterns differed as a function of attentional
      stage, stimulus modality and the features within the stimulus. Degree of
      specificity was positively predictive of SRA in both genders; however, it was not
      significantly predictive of self-reported arousal. These findings are discussed
      in the context of gendered processing of visual sexual information, including a
      discussion of implications for research designs.

PMID- 30110447
TI  - Benzothiazole heterogeneous photodegradation in nano alpha-Fe2O3/oxalate system
      under UV light irradiation.
AB  - The photodegradation of benzothiazole (BTH) in wastewater with the coexistence of
      iron oxides and oxalic acid under UV light irradiation was investigated. Results
      revealed that an effective heterogeneous photo-Fenton-like system could be set up
      for BTH abatement in wastewater under UV irradiation without additional H2O2, and
      88.1% BTH was removed with the addition of 2.0 mmol l-1 oxalic acid and 0.2 g l-1
      alpha-Fe2O3 using a 500 W high-pressure mercury lamp (365 nm). The degradation of
      BTH in the photo-Fenton-like system followed the first-order kinetic model. The
      photoproduction of hydroxyl radicals (.OH) in different systems was determined by
      high-performance liquid chromatography. Identification of transformation products
      by using liquid chromatography coupled with high resolution tandem mass
      spectrometry provided information about six transformation products formed during
      the photodegradation of BTH. Further insight was obtained by monitoring
      concentrations of the sulfate ion (SO42-) and nitrate ion (NO3-) , which
      demonstrated that the intermediate products of BTH could be decomposed
      ultimately. Based on the results, the potential photodegradation pathway of BTH
      was also proposed.

PMID- 30110448
TI  - A method for rapid testing of social learning in vampire bats.
AB  - Designing experiments on social learning using an untested behaviour or species
      requires baseline knowledge of how the animals will perform. We conducted a pilot
      study of a procedure for rapidly testing social learning in the highly social
      common vampire bat (Desmodus rotundus) using a simple maze. To create
      demonstrators, we allowed captive bats to learn to exit a three-dimensional maze,
      which reunited them with their colony as a reward. We then filmed naive bats in
      the same maze, comparing their ability to exit the maze before, during and after
      the addition of a trained demonstrator. The presence of a demonstrator increased
      the exit rates of naive bats, presumably by attracting the attention of the naive
      bats to the maze exit. Four of the five naive bats that exited in the presence of
      a demonstrator retained the ability to exit without the demonstrator. No naive
      bat exited during trials without a potential demonstrator present. This
      experimental procedure appears to be a promising approach for efficient tests of
      social learning in vampire bats because maze difficulty can be manipulated to
      adjust learning rates and each trial requires only 15 min.

PMID- 30110449
TI  - Functional materials based on molecules with hydrogen-bonding ability:
      applications to drug co-crystals and polymer complexes.
AB  - The design, synthesis and property characterization of new functional materials
      has garnered interest in a variety of fields. Materials that are capable of
      recognizing and binding with small molecules have applications in sensing,
      sequestration, delivery and property modification. Specifically, recognition of
      pharmaceutical compounds is of interest in each of the aforementioned application
      areas. Numerous pharmaceutical compounds comprise functional groups that are
      capable of engaging in hydrogen-bonding interactions; thus, materials that are
      able to act as hydrogen-bond receptors are of significant interest for these
      applications. In this review, we highlight some crystalline and polymeric
      materials that recognize and engage in hydrogen-bonding interactions with
      pharmaceuticals or small biomolecules. Moreover, as pharmaceuticals often exhibit
      multiple hydrogen-bonding sites, many donor/acceptor molecules have been
      specifically designed to interact with the drug via such multiple-point hydrogen
      bonds. The formation of multiple hydrogen bonds not only increases the strength
      of the interaction but also affords unique hydrogen-bonded architectures.

PMID- 30110450
TI  - Differential loss of components of traditional ecological knowledge following a
      primate extinction event.
AB  - Traditional ecological knowledge (TEK), an important component of the modern
      conservation toolkit, is being eroded in indigenous communities around the world.
      However, the dynamics of TEK loss in response to ecosystem change and disruption
      to social-ecological systems, and patterns of variation in vulnerability and
      resilience of different components of TEK, remain poorly understood. The Hainan
      gibbon (Nomascus hainanus), a culturally significant primate, was formerly
      distributed across Hainan Island, China, but became extinct across most of this
      range within living memory and is now restricted to a single landscape,
      Bawangling National Nature Reserve. Gibbon-specific TEK (including folktales,
      natural history information and methods of gibbon exploitation) is still present
      in indigenous communities across seven Hainanese landscapes, but statistically
      significant differences in TEK content exist between landscapes with different
      histories of gibbon persistence: respondents from Bawangling and most landscapes
      that have recently lost gibbons report more gibbon-related folktales compared
      with landscapes from which gibbons have been absent for several decades. Species
      specific folktales might have been lost more rapidly compared with other
      components of TEK because older community members are typically the 'cultural
      repositories' of stories, whereas knowledge about practical interactions with
      biodiversity might be shared more widely with younger community members.

PMID- 30110451
TI  - A new terrestrial palaeoenvironmental record from the Bering Land Bridge and
      context for human dispersal.
AB  - Palaeoenvironmental records from the now-submerged Bering Land Bridge (BLB)
      covering the Last Glacial Maximum (LGM) to the present are needed to document
      changing environments and connections with the dispersal of humans into North
      America. Moreover, terrestrially based records of environmental changes are
      needed in close proximity to the re-establishment of circulation between Pacific
      and Atlantic Oceans following the end of the last glaciation to test palaeo
      climate models for the high latitudes. We present the first terrestrial
      temperature and hydrologic reconstructions from the LGM to the present from the
      BLB's south-central margin. We find that the timing of the earliest unequivocal
      human dispersals into Alaska, based on archaeological evidence, corresponds with
      a shift to warmer/wetter conditions on the BLB between 14 700 and 13 500 years
      ago associated with the early Bolling/Allerod interstadial (BA). These
      environmental changes could have provided the impetus for eastward human
      dispersal at that time, from Western or central Beringia after a protracted human
      population standstill. Our data indicate substantial climate-induced
      environmental changes on the BLB since the LGM, which would potentially have had
      significant influences on megafaunal and human biogeography in the region.

PMID- 30110452
TI  - New information on Brindabellaspis stensioi Young, 1980, highlights morphological
      disparity in Early Devonian placoderms.
AB  - Acid-prepared specimens of the placoderm Brindabellaspis stensioi (Early Devonian
      of New South Wales, Australia) revealed placoderm endocranial anatomy in
      unprecedented detail. Brindabellaspis has become a key taxon in discussions of
      early gnathostome phylogeny, and the question of placoderm monophyly versus
      paraphyly. The anterior orientation of the facial nerve and related hyoid arch
      structures in this taxon resemble fossil osteostracans (jawless vertebrates)
      rather than other early gnathostomes. New specimens of Brindabellaspis now reveal
      the previously unknown anterior region of the skull, including an exceptionally
      elongate premedian bone forming a long rostrum, supported by a thin extension of
      the postethmo-occipital unit of the braincase. Lateral overlap surfaces indicate
      an unusual anterior position for the jaws. Digital rendering of a synchrotron
      radiation scan reveals a uniquely specialized ethmoid commissure sensory canal,
      doubled back and fused into a midline canal. The visceral surface of the
      premedian bone has a plexus of perichondral bone canals. An updated skull roof
      reconstruction of Brindabellaspis adds to the highly variable dermal skull
      patterns of the probably non-monophyletic 'acanthothoracids'. The unusual
      morphology revealed by the new specimens suggests that the earliest known reef
      fish fauna contained a diverse range of fishes with specialized ecological roles.

PMID- 30110454
TI  - Electronic structure, elasticity, Debye temperature and anisotropy of cubic WO3
      from first-principles calculation.
AB  - The electron structure, elastic constant, Debye temperature and anisotropy of
      elastic wave velocity for cubic WO3 are studied using CASTEP based on density
      functional theory. The optimized structure is consistent with previous work and
      the band gap is obtained by computing the electronic structure; the top of the
      valence band is not at the same point as the bottom of the conduction band, which
      is an indirect band-gap oxide. Electronic properties are studied from the
      calculation of band structure, densities of states and charge densities. The bulk
      and shear moduli, Young's modulus, hardness and Poisson's ratio for WO3 are
      studied by the elastic constants. We calculated acoustic wave velocities in
      different directions and estimated the Debye temperature from the acoustic
      velocity. The anisotropy of WO3 was analysed from the point of view of a pure
      wave and quasi wave.

PMID- 30110453
TI  - Response of Prochilodus nigricans to flood pulse variation in the central Amazon.
AB  - The influence of the flood pulse on fish populations has been posited, but
      infrequently tested or quantified. Here, we tested the effect of habitat on
      population size, using Prochilodus nigricans as a case study species. Floodplain
      habitat was based on the littoral zone area occupied by P. nigricans to feed. The
      magnitude of this habitat in each hydrological year, the moving littoral (ML),
      was expressed as the sum of daily littoral areas during the advancing flood
      pulse, using satellite-based passive microwave data. Annual population size was
      estimated by age class, using a dynamic age-structured model (MULTIFAN-CL) based
      on catches, effort and fish length frequencies from the Manaus-based fishery over
      12.75 years. The principal null hypothesis was that the ML, using three lag
      times, had no effect on population size of a single age class of P. nigricans.
      The population size at 29 months of age was positively related (p = 0.00030) to
      floodplain habitat (ML) earlier in the same year, when the fish were 21-27 months
      old. The result implies a density-dependent relationship for the population with
      respect to its feeding habitat. Potential mechanisms governed by flood pulse
      variation and habitat quality for this and other species using floodplain
      habitats are discussed.

PMID- 30110455
TI  - Development of low-cost non-contact structural health monitoring system for
      rotating machinery.
AB  - Condition monitoring systems are increasingly being employed in industrial
      applications to improve the availability of equipment to increase the overall
      equipment efficiency. Condition monitoring of gearboxes, a key element of
      rotating machines, ensures to continuously reduce and eliminate costs,
      unscheduled downtime and unexpected breakdowns. This study demonstrates a low
      cost microcontroller-based non-contact data acquisition system for condition
      monitoring of rotating machinery. Experimental validation of the proposed system
      was carried out by performing examination tests on a gearbox test rig. A user
      friendly graphical user interface was also developed which facilitates users to
      perform signal processing in both real-time and offline mode. The proposed system
      can perform most of the functions available in complex, stand-alone vibration
      analysers. The use of a general-purpose PC and standard programing language makes
      the system simple, economical and adaptable to a variety of problems. The tests
      show the developed system can perform properly as proposed.

PMID- 30110456
TI  - Analysing the effect of paddy rice variety on fluorescence characteristics for
      nitrogen application monitoring.
AB  - Paddy rice is one of the most important cereal crops worldwide, so it is very
      important to accurately monitor its growth status and photosynthetic efficiency.
      The nitrogen (N) level is a key factor closely related to crop growth. In this
      study, laser-induced fluorescence (LIF) technology combined with multi-variate
      analysis was applied to investigate the effect of paddy rice variety on N
      fertilizer level monitoring. Principal components analysis was conducted to
      extract the variables of the main fluorescence characteristics to identify N
      levels. Experimental results demonstrated that no nitrogen fertilizer can be
      completely identified for each paddy rice variety. In addition, other N levels
      can also be well classified based on the fluorescence characteristics. The
      relationship between the fluorescence ratio (F735/F685 : F735, and F685 denote
      the fluorescence intensity at 735 nm, and 685 nm, respectively) and leaf N
      content of different paddy rice varieties is also discussed. Experimental results
      revealed that LIF technology is an effective method of monitoring the N
      fertilizer and leaf biochemical components of paddy rice.

PMID- 30110457
TI  - Wake-induced oscillation behaviour of twin bundle conductor transmission lines.
AB  - A numerical method to simulate air flow around a bundle conductor line by means
      of the FLUENT software is presented and verified by a wind tunnel test for
      aerodynamic characteristics of a twin bundle conductor line. The lift and drag
      coefficients of the leeward sub-conductor of a twin bundle conductor varying with
      its relative position in the wake zone to the windward one under different wind
      velocities are numerically determined by the presented method. A user-defined
      subroutine of ABAQUS software is developed to apply the aerodynamic loads on each
      sub-conductor and the electromagnetic force between sub-conductors. The numerical
      simulation method for wake-induced oscillation of a bundle conductor line is
      proposed. By means of the numerical method, wake-induced oscillation processes of
      twin bundle conductor transmission lines under different parameters, including
      current intensity, spacer layout, span length and wind velocity, are numerically
      simulated. Moreover, the effects of those parameters on the oscillation
      characteristics of the lines, such as vibration mode, frequency, amplitude and
      motion trace, are discussed. The results obtained provide a fundamental basis for
      the understanding of wake-induced oscillation behaviour of twin bundle conductor
      transmission lines and the development of control technique for wake-induced
      oscillation.

PMID- 30110458
TI  - Facile synthesis of hierarchical CNF/SnO2/Ni nanostructures via self-assembly
      process as anode materials for lithium ion batteries.
AB  - Hierarchical carbon nanofibre (CNF)/SnO2/Ni nanostructures of graphitized carbon
      nanofibres and SnO2 nanocrystallines and Ni nanocrystallines have been prepared
      via divalent tin-alginate assembly on polyacrylonitrile (PAN) fibres, controlled
      pyrolysis and ball milling. Fabrication is implemented in three steps: (1)
      formation of a tin-alginate layer on PAN fibres by coating sodium alginate on PAN
      in a water medium followed by polycondensation in SnCl2 solution; (2) heat
      treatment at 450 degrees C in a nitrogen atmosphere; (3) ball milling the mixture
      of CNF/SnO2 fibres and Ni powder. The CNF/SnO2/Ni nanocomposite exhibits good
      lithium ion storage capacity and cyclability, providing a facile and low-cost
      approach for the large-scale preparation of anode materials for lithium ion
      batteries.

PMID- 30110459
TI  - The regio-selective synthesis of 10-hydroxy camptothecin norcantharidin
      conjugates and their biological activity evaluation in vitro.
AB  - A series of conjugates of 10-hydroxy camptothecin (HCPT) with functionalized
      norcantharidin derivatives were regio-selectively synthesized in the condition of
      (3-dimethylaminopropyl) ethyl-carbodiimide monohydrochloride in a moderate yield.
      The synthesized conjugate HCPT pro-drugs can also suppress cancer cell growth in
      vitro. These conjugated pro-drug constructs possess therapeutic potential as
      novel bi-functional conjugate platforms for cancer treatment.

PMID- 30110461
TI  - Characteristics of hydraulic fracture surface based on 3D scanning technology.
AB  - The surface characteristics of fractured specimens are important in hydraulic
      fracturing laboratory experiments. In this paper, we present a three-dimensional
      (3D) scanning device assembled to study these surface characteristics. Cube
      shaped rock specimens were produced in the laboratory and subjected to triaxial
      loading until the specimen split in two in a hydraulic fracturing experiment.
      Each fractured specimen was placed on a rotating platform and scanned to produce
      3D superficial coordinates of the surface of the fractured specimen. The scanned
      data were processed to produce high-precision digital images of the fractured
      model, a surface contour map and accurate values of the superficial area and
      specimen volume. The images produced by processing the 3D scanner data provided
      detailed information on the morphology of the fractured surface and mechanism of
      fracture propagation. High-precision 3D mapping of the fractured surfaces is
      essential for quantitative analysis of fractured specimens. The 3D scanning
      technology presented here is an important tool for the study of fracture
      characteristics in hydraulic fracturing experiments.

PMID- 30110460
TI  - Waptia fieldensis Walcott, a mandibulate arthropod from the middle Cambrian
      Burgess Shale.
AB  - Waptia fieldensis Walcott, 1912 is one of the iconic animals from the middle
      Cambrian Burgess Shale biota that had lacked a formal description since its
      discovery at the beginning of the twentieth century. This study, based on over
      1800 specimens, finds that W. fieldensis shares general characteristics with
      pancrustaceans, as previous authors had suggested based mostly on its overall
      aspect. The cephalothorax is covered by a flexible, bivalved carapace and houses
      a pair of long multisegmented antennules, palp-bearing mandibles, maxillules, and
      four pairs of appendages with five-segmented endopods-the anterior three pairs
      with long and robust enditic basipods, the fourth pair with proximal annulations
      and lamellae. The post-cephalothorax has six pairs of lamellate and fully
      annulated appendages which appear to be extensively modified basipods rather than
      exopods. The front part of the body bears a pair of stalked eyes with the first
      ommatidia preserved in a Burgess Shale arthropod, and a median 'labral' complex
      flanked by lobate projections with possible affinities to hemi-ellipsoid bodies.
      Waptia confirms the mandibulate affinity of hymenocarines, retrieved here as part
      of an expanded Pancrustacea, thereby providing a novel perspective on the
      evolutionary history of this hyperdiverse group. We construe that Waptia was an
      active swimming predator of soft prey items, using its anterior appendages for
      food capture and manipulation, and also potentially for clinging to epibenthic
      substrates.

PMID- 30110463
TI  - Oxidation kinetics of YBaCo4O7+delta and substituted oxygen carriers.
AB  - In this paper, the relaxation kinetics of the oxidation process of the
      YBaCo4O7+delta , Y0.95Ti0.05BaCo4O7+delta and Y0.5Dy0.5BaCo4O7+delta oxygen
      carriers is studied with isothermal reaction data. XRD analysis for fresh samples
      shows that all the samples have YBaCo4O7+delta structure. Scanning electron
      microscopy images of samples show that the samples consist of porous agglomerates
      of primary particles. Isothermal TG experiments are conducted with temperatures
      of 290 degrees C, 310 degrees C, 330 degrees C and 350 degrees C, respectively.
      It is found that the Avrami-Erofeev model describes solid-phase changes in the
      oxygen absorption process adequately. The results show that the distributed
      activation energies of the oxidation process obtained by the Avrami-Erofeev model
      are 42.079 kJ mol-1, 42.944 kJ mol-1 and 41.711 kJ mol-1 for the YBaCo4O7+delta ,
      Y0.95Ti0.05BaCo4O7+delta and Y0.5Dy0.5BaCo4O7+delta oxygen carriers,
      respectively. The kinetic model was obtained to predict the oxygen carrier
      conversion of oxygen absorption for different time durations. The kinetic
      parameters obtained here are quite vital when this material is used in reactors.

PMID- 30110462
TI  - Ceramide-transfer protein-mediated ceramide transfer is a structurally tunable
      flow-inducing mechanism with structural feed-forward loops.
AB  - This paper considers two models of ceramide-transfer protein (CERT)-mediated
      ceramide transfer at the trans-Golgi network proposed in the literature, short
      distance shuttle and neck swinging, and seeks structural (parameter-free)
      features of the two models, which rely exclusively on the peculiar interaction
      network and not on specific parameter values. In particular, it is shown that
      both models can be seen as flow-inducing systems, where the flows between pairs
      of species are tuned by the concentrations of other species, and suitable
      external inputs can structurally regulate ceramide transfer. In the short
      distance shuttle model, the amount of transferred ceramide is structurally tuned
      by active protein kinase D (PKD), both directly and indirectly, in a coherent
      feed-forward loop motif. In the neck-swinging model, the amount of transferred
      ceramide is structurally tuned by active PI4KIIIbeta, while active PKD has an
      ambivalent effect, due to the presence of an incoherent feed-forward loop motif
      that directly inhibits ceramide transfer and indirectly promotes it; the
      structural role of active PKD is to favour CERT mobility in the cytosol. It is
      also shown that the influences among key variables often have structurally
      determined steady-state signs, which can help falsify the models against
      experimental traces.

PMID- 30110465
TI  - Correction to 'An empirical measure of nonlinear strain for soft tissue
      indentation'.
AB  - [This corrects the article DOI: 10.1098/rsos.170894.].

PMID- 30110464
TI  - Novel amphiphilic polyvinylpyrrolidone functionalized silicone particles as
      carrier for low-cost lipase immobilization.
AB  - The high catalytic activity, specificity and stability of immobilized lipase have
      been attracting great interest. How to reduce the cost of support materials has
      always been a hot topic in this field. Herein, for the development of low-cost
      immobilized lipase, we demonstrate an amphiphilic polyvinylpyrrolidone (PVP)
      grafted on silicone particle (SP) surface materials (SP-PVP) with a rational
      design based on interfacial activation and solution polymerization. Meanwhile,
      hydrophilic pristine SP and hydrophobic polystyrene-corded silicone particles (SP
      Pst) were also prepared for lipase immobilization. SP-PVP was characterized by X
      ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy,
      Fourier transform infrared spectroscopy and thermogravimetry. Our results
      indicated that the lipase loading amount on the SP-PVP composites was about 215
      mg of protein per gram. In the activity assay, the immobilized lipase SP-PVP@CRL
      exhibited higher catalysis activity and better thermostability and reusability
      than SP@CRL and SP-Pst@CRL. The immobilized lipase retained more than 54% of its
      initial activity after 10 times of re-use and approximately trended to a steady
      rate in the following cycles. By introducing the interesting amphiphilic polymer
      to this cheap and easily obtained SP surface, the relative performance of the
      immobilized lipase can be significantly improved, facilitating interactions
      between the low-cost support materials and lipase.

PMID- 30110466
TI  - Dynamic analysis of liquid annular seals with herringbone grooves on the rotor
      based on the perturbation method.
AB  - Annular seals have significant effects on the hydraulic and rotordynamic
      performances of turbomachinery. In this paper, an analysis method for calculating
      the leakage flow rates and dynamic characteristics of liquid annular seals with
      herringbone grooves on the rotor is proposed and verified. Leakage flow rates and
      dynamic characteristics of the model seals under different operating conditions
      are theoretically analysed and compared with those of plain and spiral-grooved
      seals of the same size. In addition, the influence of geometric parameters such
      as spiral angle and the lengths of the constituent parts on the sealing and
      rotordynamic coefficients of seals with herringbone grooves are also discussed.
      The results show that seals with herringbone grooves have better sealing
      performance, while providing better support actions and damping characteristics
      than the other two seal types under the same operating conditions. The seal
      geometric parameters including spiral angle, the lengths of the constituent parts
      and the clearance value have a significant influence on the dynamic
      characteristics of seals with herringbone grooves.

PMID- 30110467
TI  - Analysis of crotonaldehyde puff-by-puff release in mainstream cigarette smoke
      under various smoking regimens by high-performance liquid chromatography with the
      modified QuEChERS method.
AB  - To study puff-by-puff release characteristics of crotonaldehyde in mainstream
      cigarette smoke under diverse intensive smoking regimens, we designed an RM20H
      smoking machine with a puff-by-puff smoke collection unit to automatically trap
      crotonaldehyde in the mainstream cigarette smoke. Using this process, we trapped,
      puff-by-puff, crotonaldehyde in mainstream smoke generated by different smoking
      regimens and quantitatively analysed the levels of crotonaldehyde using high
      performance liquid chromatography with a modified QuEChERS sample pretreatment
      method. On the basis of the crotonaldehyde in each puff, we determined
      crotonaldehyde's puff-by-puff release characteristics. The results showed that
      crotonaldehyde's puff-by-puff release remained nearly constant for the
      International Organization for Standardization mode while increased polynomial
      trend was seen (n >= 6) under the Massachusetts and Health Canada smoking
      regimens. The equation fit for various regimens was good (R2 > 0.9192). Release
      characteristics by puff were classified into four categories: (1) first, second
      and third puffs; (2) fourth and fifth puffs; (3) sixth puff; and (4) seventh and
      eighth puffs.

PMID- 30110468
TI  - Sensing study of quinoxaline analogues with theoretical calculation, single
      crystal X-ray structure and real application in commercial fruit juices.
AB  - Single-crystal X-ray structures of dimeric quinoxaline aldehyde (QA), quinoxaline
      dihydrazone (DHQ) and HQNM (Goswami S et al. 2013 Tetrahedron Lett.54, 5075-5077.
      (doi:10.1016/j.tetlet.2013.07.051); Goswami S et al. 2014 RSC Adv.4, 20 922-20
      926. (doi:10.1039/C4RA00594E); Goswami S et al. 2014 New J. Chem.38, 6230-6235.
      (doi:10.1039/C4NJ01498G)) are reported along with the theoretical study. Among
      them, QA is not acting as an active probe, but DHQ and HQNM are serving as
      selective and sensitive probe for the Fe3+ cation and the Ni2+ cation,
      respectively. DHQ can also detect the Fe3+ in commercial fruit juices (grape and
      pomegranate).

PMID- 30110469
TI  - Correction to 'Investigation on preferably oriented abnormal growth of CdSe
      nanorods along (0002) plane synthesized by henna leaf extract-mediated green
      synthesis'.
AB  - [This corrects the article DOI: 10.1098/rsos.171430.].

PMID- 30110470
TI  - A novel polyamine-type starch/glycidyl methacrylate copolymer for adsorption of
      Pb(II), Cu(II), Cd(II) and Cr(III) ions from aqueous solutions.
AB  - A novel polyamine-type starch/glycidyl methacrylate (GMA) copolymer with a high
      capacity for the adsorption of heavy metal ions was prepared via graft
      copolymerization of GMA and corn starch and a subsequent amination reaction
      between amino group of diethylenetriamine and epoxy group in GMA. The copolymers
      were characterized by Fourier transform infrared spectrometry, X-ray diffraction
      and scanning electron microscopy, and adsorption properties on modified starch of
      Cu(II), Pb(II), Cd(II) and Cr(III) were studied. By analysing the relationship
      between adsorption capacity and pH, adsorption isotherms and adsorption kinetics,
      it is proved that the adsorption of the four metal ions is mainly based on the
      chemical adsorption of coordination. The maximum adsorption capacities of the
      copolymer were up to 2.33, 1.25, 0.83 and 0.56 mmol g-1 for Cu(II), Pb(II),
      Cd(II) and Cr(III), respectively. The adsorption of the four concerned metal ions
      was hardly affected by common coexisting ions such as Na(I), K(I), Ca(II) and
      Mg(II), whereas it was slightly decreased when Fe(II) and Zn(II) coexisted in the
      solution, which illustrates the selective adsorption of Cu(II), Pb(II), Cd(II)
      and Cr(III) from wastewater. After 10 cycles of adsorption-desorption
      experiments, there was no significant change in the adsorption capacity,
      indicating that the polyamine-type starch/GMA copolymer has high adsorption
      capacity and good reusability.

PMID- 30110472
TI  - Correction to 'Speciation over the edge: gene flow among non-human primate
      species across a formidable biogeographic barrier'.
AB  - [This corrects the article DOI: 10.1098/rsos.170351.].

PMID- 30110471
TI  - The effect of alkali-soluble lignin on purified core cellulase and hemicellulase
      activities during hydrolysis of extractive ammonia-pretreated lignocellulosic
      biomass.
AB  - Removing alkali-soluble lignin using extractive ammonia (EA) pretreatment of corn
      stover (CS) is known to improve biomass conversion efficiency during enzymatic
      hydrolysis. In this study, we investigated the effect of alkali-soluble lignin on
      six purified core glycosyl hydrolases and their enzyme synergies, adopting 31
      enzyme combinations derived by a five-component simplex centroid model, during EA
      CS hydrolysis. Hydrolysis experiment was carried out using EA-CS(-) (approx. 40%
      lignin removed during EA pretreatment) and EA-CS(+) (where no lignin was
      extracted). Enzymatic hydrolysis experiments were done at three different enzyme
      mass loadings (7.5, 15 and 30 mg protein g-1 glucan), using a previously
      developed high-throughput microplate-based protocol, and the sugar yields of
      glucose and xylose were detected. The optimal enzyme combinations (based on %
      protein mass loading) of six core glycosyl hydrolases for EA-CS(-) and EA-CS(+)
      were determined that gave high sugar conversion. The inhibition of lignin on
      optimal enzyme ratios was studied, by adding fixed amount of alkali-soluble
      lignin fractions to EA-CS(-), and pure Avicel, beechwood xylan and evaluating
      their sugar conversion. The optimal enzyme ratios that gave higher sugar
      conversion for EA-CS(-) were CBH I: 27.2-28.2%, CBH II: 18.2-22.2%, EG I: 29.2
      34.3%, EX: 9.0-14.1%, betaX: 7.2-10.2%, betaG: 1.0-5.0% (at 7.5-30 mg g-1 protein
      mass loading). Endoglucanase was inhibited to a greater extent than other core
      cellulases and xylanases by lignin during enzyme hydrolysis. We also found that
      alkali-soluble lignin inhibits cellulase more strongly than hemicellulase during
      the course of enzyme hydrolysis.

PMID- 30110473
TI  - Synthesis of 1,8-naphthalimide-based probes with fluorescent switch triggered by
      flufenamic acid.
AB  - In this work, we report the synthesis of novel fluorescent molecules, based on
      1,8-naphthalimide thio- and amino-derivatives, designed to display an OFF-ON and
      ON-OFF photoelectron transfer fluorescence switch upon interaction with a proton
      donor drug. We have functionalized the new probes to allow easy formation of a
      covalent link to polymer matrices, for future applications as drug delivery
      sensors. We have investigated the fluorescent switch of the new probes using
      flufenamic acid (FA, pKa 3.65), a water insoluble, non-steroidal anti
      inflammatory drug, as a model drug and proton source. The rapid interaction of
      the new probes with FA resulted in fluorescence enhancement or decrease and a
      large Stokes shift, all of which allowed the detection of the drug in the
      nanomolar range. The new 1,8-naphthalimide fluorescent dyes reported in this work
      are interesting tools for the detection and quantification of acidic drugs and
      biomolecules.

PMID- 30110474
TI  - Tuberculosis-like respiratory infection in 245-million-year-old marine reptile
      suggested by bone pathologies.
AB  - An absence of ancient archaeological and palaeontological evidence of pneumonia
      contrasts with its recognition in the more recent archaeological record. We
      document an apparent infection-mediated periosteal reaction affecting the dorsal
      ribs in a Middle Triassic eosauropterygian historically referred to as
      'Proneusticosaurus' silesiacus. High-resolution X-ray microtomography and
      histological studies of the pathologically altered ribs revealed the presence of
      a continuous solid periosteal reaction with multiple superficial blebs
      (protrusions) on the visceral surfaces of several ribs. Increased vascularization
      and uneven lines of arrested growth document that the pathology was the result of
      a multi-seasonal disease. While visceral surface localization of this periosteal
      reaction represents the earliest identified evidence for pneumonia, the blebs may
      have an additional implication: they have only been previously recognized in
      humans with tuberculosis (TB). Along with this diagnosis is the presence of focal
      vertebral erosions, parsimoniously compared to vertebral manifestation of TB in
      humans.

PMID- 30110476
TI  - How silanization influences aggregation and moisture sorption behaviours of
      silanized silica: analysis of porosity and multilayer moisture adsorption.
AB  - Based on the results of nitrogen adsorption and dynamic vapour sorption as well
      as analysis by the Hailwood-Horrobin (H-H) model, the effects of gamma
      methacryloxypropyltrimethoxysilane (MPTS) on the agglomeration and moisture
      sorption properties of fumed silica particles were investigated. After adding
      various concentrations (2%, 4%, 6% and 8%) of MPTS, different degrees of
      silanization were obtained by showing various ?OH group contents on the silica
      surface, which resulted in silica agglomerates with different porous structures.
      The bigger mesopores in the unmodified silica agglomerates became smaller and
      finally disappeared after MPTS modification and the Bruanuer-Emmett-Teller
      surface area decreased more gradually with an increase in MPTS concentration. The
      H-H model fitted the sorption isotherms very well, and both hydrated water and
      dissolved water showed decreasing trends with the increase in MPTS concentration,
      showing reduced hygroscopicity. Up to 6% MPTS, the ?OH groups decreased with
      increasing MPTS concentration, as indicated by reduced Kh and W parameters, while
      at 8% MPTS an extensive self-condensation of MPTS occurred. Adsorption hysteresis
      appeared for moisture sorption on silanized silica, especially at low relative
      humidity values and at low MPTS concentrations, which could be explained by a
      synergistic effect of the surface ?OH group content and pore characteristics.
      These results could aid our understanding of the applications of silane-modified
      silica particles.

PMID- 30110475
TI  - Discrimination of volatiles in herbal formula Baizhu Shaoyao San before and after
      processing using needle trap device with multivariate data analysis.
AB  - To characterize the chemical differences of volatile components between crude and
      processed Baizhu Shaoyao San (BSS), a classical Chinese herbal formula that is
      widely applied in the treatment of gastrointestinal diseases, we developed a gas
      chromatography-mass spectrometry-based needle trap device combined with
      multivariate data analysis to globally profile volatile components and rapidly
      identify differentiating chemical markers. Using a triple-bed needle packed with
      Carbopack X, DVB and Carboxen 1000 sorbents, we identified 121 and 123 compounds,
      respectively, in crude and processed BSS. According to the results of principal
      component analysis and orthogonal partial least-squares discriminant analysis,
      crude and processed BSS were successfully distinguished into two groups with good
      fitting and predicting parameters. Furthermore, 21 compounds were identified and
      adopted as potential markers that could be employed to quickly differentiate
      these two types of samples using S-PLOT and variable importance in projection
      analyses. The established method can be applied to explain the chemical
      transformation of Chinese medicine processing in BSS and further control the
      quality and understand the processing mechanism of Chinese herbal formulae.
      Besides, the triple-bed needle selected and optimized in this study can provide a
      valuable reference for other plant researches with similar components.
      Furthermore, the systematic research on compound identification and marker
      discrimination of the complex components in crude and processed BSS could work as
      an example for other similar studies, such as composition changes in one plant
      during different growth periods, botanical characters of different medicinal
      parts in same kind of medicinal herbs and quality identification of one species
      of medicinal herb from different regions.

PMID- 30110477
TI  - Correction to 'Determination of carcinogenic herbicides in milk samples using
      green non-ionic silicone surfactant of cloud point extraction and
      spectrophotometry'.
AB  - [This corrects the article DOI: 10.1098/rsos.171500.].

PMID- 30110478
TI  - Metal-free selective mono-halodecarboxylation of heteroarenes under mild
      conditions.
AB  - The halodecarboxylation of heteroarene carboxylic acids by treatment with N
      bromosuccinimide or N-chlorosuccinimide was performed. This procedure provides a
      convenient route to synthetically useful mono-halogenated heteroarene
      intermediates such as halo-indoles, -aza-indoles, -indazoles and -aza-indazoles.
      The mild conditions employed and simple protocol provides an advantage over
      traditional halodecarboxylation procedures that require expensive and toxic metal
      catalysts, basic conditions, time-consuming intermediate isolation and elevated
      reaction temperatures.

PMID- 30110479
TI  - Thickness-dependent humidity sensing by poly(vinyl alcohol) stabilized Au-Ag and
      Ag-Au core-shell bimetallic nanomorph resistors.
AB  - We herein report a simple chemical route to prepare Au-Ag and Ag-Au core-shell
      bimetallic nanostructures by reduction of two kinds of noble metal ions in the
      presence of a water-soluble polymer such as poly(vinyl alcohol) (PVA). PVA was
      intentionally chosen as it can play a dual role of a supporting matrix as well as
      stabilizer. The simultaneous reduction of metal ions leads to an alloy type of
      structure. Ag(c)-Au(s) core-shell structures display tendency to form prismatic
      nanostructures in conjunction with nanocubes while Au(c)-Ag(s) core-shell
      structures show formation of merely nanocubes. Although UV-visible spectroscopy
      and X-ray photoelectron spectroscopy analyses of the samples typically suggest
      the formation of both Ag(c)-Au(s) and Au(c)-Ag(s) bimetallic nanostructures, the
      definitive evidence comes from high-resolution transmission electron microscopy
      high-angle annular dark field elemental mapping in the case of Au(c)-Ag(s)
      nanomorphs only. The resultant nanocomposite materials are used to fabricate
      resistors on ceramic rods having two electrodes by drop casting technique. These
      resistors are examined for their relative humidity (RH) response in the range (2
      93% RH) and both the bimetallic nanocomposite materials offer optimized
      sensitivity of about 20 Kohm/% RH and 300 ohm/% RH at low and higher humidity
      conditions, respectively, which is better than that of individual nanoparticles.

PMID- 30110480
TI  - Effects of thermal treatments on 10 major phenolics and their antioxidant
      contributions in Acer truncatum leaves and flowers.
AB  - This study aimed to investigate effects of thermal treatments on major phenolics
      and their antioxidant contributions in Acer truncatum leaves and flowers (ATL and
      ATF, respectively). With ultra performance liquid chromatography-diode array
      detector-quadrupole time-of-flight-mass spectrometer/mass spectrometer, phenolic
      compositions of ATF were first characterized and compared with those of ATL. An
      optimized high performance liquid chromatography fingerprint was then
      established, and 10 major phenolics existing in both ATL and ATF were quantified.
      Gallic acid derivatives and flavonol-3-O-glycosides were found to be their
      dominant phenolic constituents, with the former being key constituents which was
      affected by thermal treatments and further influencing the variations of total
      phenols. Moreover, the mechanism underlining the changes of phenolics in ATL and
      ATF by the treatments was characterized as a thermolhydrolysis process. During
      thermal treatments, polymerized gallotannins were hydrolysed to 1,2,3,4,6
      pentakis-O-galloyl-beta-d-glucose, ethyl gallate and gallic acid, resulting in
      more than fivefold and twofold increase of their contents in ATL and ATF,
      respectively. By contrast, contents and antioxidant contributions of flavonol-3-O
      glycosides gradually decreased during the process.?absbreak Overall, this is, to
      our knowledge, the first report on the effects of thermal treatments on phenolics
      and their antioxidant contributions in ATL and ATF, and the three gallic acid
      derivatives with potentially higher bioactivity could be efficiently achieved by
      thermal treatments.

PMID- 30110481
TI  - Surface chemical changes analysis of UV-light irradiated Moso bamboo
      (Phyllostachys pubescens Mazel).
AB  - Photodegradation is one of the key factors that affect bamboo material
      application in the exterior environment. Photo radiation will cause chemical
      degradation, discoloration and cracks on the bamboo surface, thus resulting in
      weakened strength. The study imitated the accelerated weathering effect of Moso
      bamboo in sunlight by using UV 313 light. Results showed that after UV
      irradiation, lignin content decreased sharply. Lignin degradation products are
      commonly rich in double bonds conjugated with benzene rings; they absorb UV light
      and shift surface spectral absorbency from the visible to the UV region and play
      an important role in the first stage of reddish-yellow discoloration. The
      photochemical reactions were very rapid at the beginning and then slowed down
      after one week. The degraded products covered the surface and protected the inner
      layer from further degradation. The surface colour turned grey and lighter with
      erosion of degradation products when the experimental time was extended.

PMID- 30110482
TI  - Technology networks: the autocatalytic origins of innovation.
AB  - We analyse the autocatalytic structure of technological networks and evaluate its
      significance for the dynamics of innovation patenting. To this aim, we define a
      directed network of technological fields based on the International Patents
      Classification, in which a source node is connected to a receiver node via a link
      if patenting activity in the source field anticipates patents in the receiver
      field in the same region more frequently than we would expect at random. We show
      that the evolution of the technology network is compatible with the presence of a
      growing autocatalytic structure, i.e. a portion of the network in which
      technological fields mutually benefit from being connected to one another. We
      further show that technological fields in the core of the autocatalytic set
      display greater fitness, i.e. they tend to appear in a greater number of patents,
      thus suggesting the presence of positive spillovers as well as positive
      reinforcement. Finally, we observe that core shifts take place whereby different
      groups of technology fields alternate within the autocatalytic structure; this
      points to the importance of recombinant innovation taking place between close as
      well as distant fields of the hierarchical classification of technological
      fields.

PMID- 30110483
TI  - Energetics and electronic structures of perylene confined in carbon nanotubes.
AB  - The energetics and geometries of perylene encapsulated in carbon nanotubes (CNTs)
      have been investigated employing density functional theory using the generalized
      gradient approximation combined with the van der Waals correction. Our
      calculations show that the encapsulated perylene molecules possess two metastable
      molecular conformations with respect to the CNT wall, which are almost degenerate
      with each other. A standing conformation, with respect to the CNT wall, is the
      ground state conformation for a semiconducting (19,0)CNT, while a lying
      conformation is the ground state for a metallic (11,11)CNT. Cooperation and
      competition between perylene-perylene and perylene-CNT interactions cause these
      possible perylene conformations inside CNTs. However, the electronic structure of
      the CNT encapsulating the perylene molecules is found to be insensitive to the
      molecular conformation.

PMID- 30110484
TI  - Forensic efficiency estimate and phylogenetic analysis for Chinese Kyrgyz ethnic
      group revealed by a panel of 21 short tandem repeats.
AB  - Short tandem repeats (STRs) with a high level of polymorphisms and convenient
      detection method play an indispensable role in human population and forensic
      genetics. Recently, we detected the 21 autosomal non-combined DNA index system
      (non-CODIS) STR loci in a Kyrgyz ethnic group, calculated their forensic
      parameters and analysed its genetic relationships with reference populations from
      China. In total, 168 alleles were observed at 21 non-CODIS STRs with
      corresponding allelic frequencies from 0.0016 to 0.4788. No significant
      deviations at these STRs were observed from the Hardy-Weinberg equilibrium. The
      values of cumulative power of discrimination and probability of exclusion for all
      the 21 non-CODIS STRs were 0.99999999999999999998835 and 0.9999994002,
      respectively. Furthermore, the analyses of phylogenetic trees, genetic distances
      and interpopulation differentiations demonstrated that the Kyrgyz group had
      relatively close genetic relationships with the Uygur and Kazak groups. These 21
      non-CODIS STRs were characterized by high genetic diversities in the Kyrgyz group
      and could be applied as a robust tool for individual identification and kinship
      testing in forensic sciences.

PMID- 30110485
TI  - Exploring the potential pharmacodynamic material basis and pharmacologic
      mechanism of the Fufang-Xialian-Capsule in chronic atrophic gastritis by network
      pharmacology approach based on the components absorbed into the blood.
AB  - In this study, a new network pharmacology approach based on the components
      absorbed into the blood was used to investigate the pharmacodynamic material
      basis and the pharmacologic mechanism of the Fufang-Xialian-Capsule (FXL) in
      treating chronic atrophic gastritis (CAG). Initially, we confirmed the components
      absorbed into the blood by ultra-high-performance liquid chromatography coupled
      with quadrupole time-of-flight mass spectrometry. Then, the network approach,
      which was based on the results of components absorbed into the blood, was used to
      analyse the pharmacodynamic material basis and the pharmacologic mechanism of FXL
      on treating CAG. As a result, 22 absorbed components were found in rat plasma.
      Given the results of the absorption analysis of the components, eight pathways
      associated with CAG development were found. The targets linked to these pathways
      are the drug targets of FXL in CAG treatment. The components associated with
      these targets are the potential pharmacodynamic material basis and exert synergy
      in regulating pathways during CAG treatment.

PMID- 30110486
TI  - One-step synthesis of OH-TiO2/TiOF2 nanohybrids and their enhanced solar light
      photocatalytic performance.
AB  - TiO2/TiOF2 nanohybrids were quickly synthesized through a hydrothermal process
      using titanium n-butoxide (TBOT), ethanol (C2H5OH) and hydrofluoric acid as
      precursors. The prepared nanohybrids underwent additional NaOH treatment (OH
      TiO2/TiOF2) to enhance their photocatalytic performance. In this paper, the
      mechanism of NaOH affecting the pathway of transformation from TBOT (Ti
      precursor) to TiO2 nanosheets was discussed. The synthesized TiO2/TiOF2 and OH
      TiO2/TiOF2 were characterized by field emission scanning electron microscopy (FE
      SEM), high-resolution transmission electron microscopy (HRTEM), X-ray diffraction
      pattern (XRD), Fourier infrared spectroscopic analysis (FT-IR), Photoluminescence
      (PL) emission spectra and UV-visible diffuse reflection spectra (UV-vis DRS). The
      photocatalytic activity and stability of synthesized samples were evaluated by
      degradation of methylene blue (MB) under the simulated solar light. The results
      showed that a larger ratio of TiO2 to TiOF2 in TiO2/TiOF2 and OH-TiO2/TiOF2
      nanohybrids could allow for even higher MB conversion compared with only TiO2
      nanosheets. NaOH treatment can wash off the F ions from TiOF2 and induce this
      larger ratio. The highest efficiency of MB removal was just above 90% in 1 h.
      Lower electron-hole pairs recombination rate is the dominant factor that induces
      the photocatalytic performance enhancement of TiO2/TiOF2 nanohybrids. The
      synthesized OH-TiO2/TiOF2 nanohybrids exhibit great potential in the abatement of
      organic pollutants.

PMID- 30110487
TI  - Carbon nanotube-based flexible electrothermal film heaters with a high heating
      rate.
AB  - High-performance, flexible film heaters with carbon nanotube transparent
      conducting films are easily fabricated by both a rod-coating method and a
      spraying method. The main conclusion we have reached is that the film
      demonstrates a heating rate of 6.1 degrees C s-1 at 35 V and sheet resistance as
      low as 94.7  Omega  sq-1 with 72.04% optical transmittance at a wavelength of 550
      nm by the spraying method after a series of post-treatment processes with acid
      and distilled water. Then, we adopt a mathematical method of nonlinear fitting to
      simulate the collected experimental data and the functions effectively.
      Furthermore, through analysis of the formula, the correlation between temperature
      and time is well explained. Therefore, carbon nanotube-based, flexible,
      transparent heaters exhibit high electrothermal performance and are expected to
      find different applications, e.g. various functional devices such as heating
      materials, heatable smart windows or dining tables.

PMID- 30110488
TI  - Rapid degradation of malachite green by CoFe2O4-SiC foam under microwave
      radiation.
AB  - This study demonstrated rapid degradation of malachite green (MG) by a microwave
      (MW)-induced enhanced catalytic process with CoFe2O4-SiC foam. The catalyst was
      synthesized from CoFe2O4 particles and SiC foam by the hydrothermal method. X-ray
      diffraction and scanning electron microscopy techniques were used to confirm that
      CoFe2O4 particles were settled on the surface of SiC foam. In this experiment, a
      novel fixed-bed reactor was set up with this catalyst for a continuous flow
      process in a MW oven. The different parameters that affect the MW-induced
      degradation rate of MG were explored. The MW irradiation leads to the effective
      catalytic degradation of MG, achieving 95.01% degradation within 5 min at pH 8.5.
      At the same time, the good stability and applicability of CoFe2O4-SiC foam for
      the degradation process were also discussed, as well as the underlying mechanism.
      In brief, these findings make the CoFe2O4-SiC foam an excellent catalyst that
      could be used in practical rapid degradation of MG.

PMID- 30110489
TI  - Divergent coevolutionary trajectories in parent-offspring interactions and
      discrimination against brood parasites revealed by interspecific cross-fostering.
AB  - In animal families, parents are expected to adapt to their offspring's traits,
      and offspring, in turn, are expected to adapt to the environment circumscribed by
      their parents. However, whether such coevolutionary trajectories differ between
      closely related species is poorly understood. Here, we employ interspecific cross
      fostering in three species of burying beetles, Nicrophorus orbicollis,
      Nicrophorus pustulatus and Nicrophorus vespilloides, to test for divergent co
      adaptation among species with different degrees of offspring dependency on
      parental care, and to test whether they are able to discriminate against
      interspecific parasites. We found that offspring survival was always higher when
      offspring were reared by conspecific rather than heterospecific parents. In the
      case of N. orbicollis raising N. pustulatus, none of the larvae survived.
      Overall, these results indicate that parent and offspring traits have diverged
      between species, and that the differential survival of conspecific and
      heterospecific larvae is because of improper matching of co-adapted traits, or,
      in the case of N. orbicollis with larval N. pustulatus, because of selection on
      parents to recognize and destroy interspecific brood parasites. We suggest that
      burying beetles experiencing a high risk of brood parasitism have evolved direct
      recognition mechanisms that enable them to selectively kill larvae of potential
      brood parasites.

PMID- 30110490
TI  - Muscle-tendon unit length changes differ between young and adult sprinters in the
      first stance phase of sprint running.
AB  - The aim of this study was to compare young and adult sprinters on several
      biomechanical parameters that were previously highlighted as performance-related
      and to determine the behaviour of several muscle-tendon units (MTU) in the first
      stance phase following a block start in sprint running. The ground reaction force
      (GRF) and kinematic data were collected from 16 adult and 21 young well-trained
      sprinters. No difference between the groups was found in some of the previously
      highlighted performance-related parameters (ankle joint stiffness, the range of
      dorsiflexion and plantar flexor moment). Interestingly, the young sprinters
      showed a greater maximal and mean ratio of horizontal to total GRF, which was
      mainly attributed to a greater horizontal GRF relative to body mass and resulted
      in a greater change in horizontal centre of mass (COM) velocity during the stance
      phase in the young compared with the adult sprinters. Results from the MTU length
      analyses showed that adult sprinters had more MTU shortening and higher maximal
      MTU shortening velocities in all plantar flexors and the rectus femoris. Although
      previously highlighted performance-related parameters could not explain the
      greater 100 m sprinting times in the adult sprinters, differences were found in
      the behaviour of the MTU of the plantar flexors and rectus femoris during the
      first stance phase. The pattern of length changes in these MTUs provides ideal
      conditions for the use of elastic energy storage and release for power
      enhancement.

PMID- 30110491
TI  - A new method of N to C sequential ligation using thioacid capture ligation and
      native chemical ligation.
AB  - Sequential peptide ligation strategy becomes more and more important in large
      protein or long peptides chemical synthesis due to the limited peptide/protein
      size obtained by solid phase synthesis of individual peptides or even one-step
      peptide ligation. Herein, we developed an alternative method which could perform
      the sequential peptide ligation of several segments from N to C direction based
      on the combined use of thioacid capture ligation and native chemical ligation.
      The sweet protein monellin was produced through this strategy on a scale of multi
      milligrams.

PMID- 30110493
TI  - A bright-not bleak-future for family medicine.

PMID- 30110492
TI  - A facile synthesis of cysteine-based diketopiperazine from thiol-protected
      precursor.
AB  - l-Cysteine is one of the most promising biomass-based building blocks with great
      potential applications. Herein, we report a versatile synthetic route to produce
      cysteine-based 2,5-diketopiperazine (DKP) with good yield from the thiol-ene
      click reaction of l-cysteine and commercially available acrylates, followed by
      dimerization of the amino acid intermediates. The achieved DKP diastereomers were
      successfully separated and fully characterized by spectroscopic methods.
      Moreover, the chiroptical property of DKP in the presence of various metal ions
      was investigated by circular dichroism spectroscopy. The potential application of
      the optically active cysteine-based DKP as a chiral probe for detection of silver
      ion in water has been demonstrated.

PMID- 30110494
TI  - Beat the heat: Identification and Tx of heat-related illness.
AB  - The prompt identification and treatment of heat-related illnesses and expedited
      transport to a higher level of care can be lifesaving. This article serves as a
      go-to guide.

PMID- 30110495
TI  - Standardizing your approach to dizziness and vertigo.
AB  - First, determine whether the sensation the patient is experiencing is dizziness
      or true vertigo. Then eliminate ominous causes from the array of benign ones.

PMID- 30110496
TI  - Combine these screening tools to detect bipolar depression.
AB  - Used together, brief assessment tools, such as the PDQ9 and MDQ, have greater
      sensitivity and accuracy than clinician assessment alone.

PMID- 30110497
TI  - Anterolateral hip pain . no specific injury . Dx?

PMID- 30110498
TI  - PURL: Time to switch to nonsterile gloves for these procedures?
AB  - Are sterile gloves worth the extra cost for common cutaneous surgeries? This
      systematic review and meta-analysis provides answers.

PMID- 30110499
TI  - Photo Rounds: Painful blisters on fingertips and toes.
AB  - Our patient had visited the emergency department for painful blisters on her
      fingertips and toes. A follow-up visit to our clinic unearthed the cause.

PMID- 30110500
TI  - Nonpharmacologic treatment of chronic pain: What works?
AB  - Which therapies should you recommend for chronic low back pain, osteoarthritis,
      or fibromyalgia? This review-with 3 handy tables-summarizes the evidence.

PMID- 30110501
TI  - TEAM approach reduced wait time, improved "face" time.
AB  - An experimental care delivery model shows how staffing and role adjustments can
      enrich the health care experience for patients, staff, and physicians.

PMID- 30110502
TI  - 13 weeks' gestation . heart palpitations . chest tightness . Dx?

PMID- 30110503
TI  - Clinical Inquiries: What's the best secondary treatment for patients who fail
      initial triple therapy for H pylori?
AB  - Treating patients with Helicobacter pylori infection who have failed
      clarithromycin-based triple therapy with either levofloxacin-based triple therapy
      (with amoxicillin and a proton pump inhibitor [PPI]) or a bismuth-based quadruple
      therapy produces cure rates of 75% to 81%. Ten-day regimens produce higher cure
      rates than 7-day regimens. Repeating the initial clarithromycin-based triple
      therapy cures fewer than half of patients (strength of recommendation [SOR]: A,
      meta-analyses of randomized controlled trials [RCTs]).

PMID- 30110507
TI  - Using data linkage to report surgical treatment of breast cancer in Canada.
AB  - BACKGROUND: National population information about the surgical treatment rate for
      primary cancers, including breast cancer, has remained a significant data gap in
      Canada. This gap has implications for cancer care planning and evaluating health
      system performance. New linkages between the Canadian Cancer Registry and
      hospital discharge records were conducted by Statistics Canada in 2016. Using
      already existing, routinely collected health administrative data, these linkages
      allow viable reporting of surgical cancer treatment for the first time for all
      provinces and territories (except Quebec). DATA AND METHODS: Hospital record
      information about type and date of surgical treatment of tumours was provided by
      information from linked data. These linked data reported 50,740 incident primary
      malignant breast tumours diagnosed between January 1, 2010, and December 31,
      2012, among females aged 19 years or older. The unadjusted treatment rate for
      primary surgical intervention within one year was calculated as the proportion of
      total tumours that were linkable to hospital records. RESULTS: For three combined
      years (2010, 2011 and 2012), 88.3% (N=44,780) of patients overall received at
      least one surgical treatment. Variations to the surgical rate occurred across
      jurisdictions, with the highest rate at 91-92% for Prince Edward Island,
      Newfoundland and Labrador, British Columbia and New Brunswick. Generally, there
      was an inverse gradient between surgical treatment rate and tumour stage.
      DISCUSSION: The surgical treatment rate of new primary breast cancers varied
      across provinces and territories from 2010 to 2012. New linked data could be used
      to further identify geographic and demographic inequities in terms of receiving
      surgical cancer treatment and contribute to the evaluation of cancer system
      performance and outcomes.

PMID- 30110508
TI  - Canadians vulnerable to workplace noise.
AB  - BACKGROUND: Health and safety legislation is designed to protect workers from
      hazards, including excessive noise. However, some workers are not required to use
      hearing protection when exposed to loud noise and may be vulnerable to adverse
      outcomes, including hearing difficulties and tinnitus. DATA AND METHODS: Data for
      19- to 79-year-olds (n=6,571) were collected from 2012 through 2015 as part of
      the Canadian Health Measures Survey. People exposed to loud workplace noise were
      defined as those who had to raise their voices to communicate at arm's length.
      Vulnerable workers were defined as those who were not required to use hearing
      protection when working in noisy environments and who only used hearing
      protection sometimes, rarely or never. RESULTS: An estimated 11 million Canadians
      (43%) have worked in noisy environments, and over 6 million of them (56%) were
      classified as vulnerable to workplace noise. Although the percentage of
      vulnerable women (72%) was greater than that of men (48%), men outnumbered women
      in these circumstances at 3.7 million, compared with 2.4 million. The self
      employed were more likely than employees to be vulnerable, as were those in white
      collar versus blue-collar occupations. Vulnerable workers were more likely to
      report hearing difficulties and tinnitus than those who had never worked in a
      noisy environment. DISCUSSION: A large percentage of workers exposed to noisy
      workplaces were vulnerable because hearing protection was neither required nor
      routinely used. Further work is required to assess whether this reflects gaps in
      health and safety legislation or its implementation.

PMID- 30110509
TI  - Brief periods of inactivity reduce leg microvascular, but not macrovascular,
      function in healthy young men.
AB  - NEW FINDINGS: What is the central question of this study? We aimed to examine leg
      vascular responses to brief periods of inactivity. What is the main finding and
      its importance? We demonstrate that a mere 10 min of sitting is sufficient to
      impair leg microvascular function (reactive hyperaemia). However, conduit artery
      vasodilatation (flow-mediated dilatation) was unaffected, indicating maintained
      macrovascular function. Interestingly, immobile supine rest also resulted in a
      reduction in microvascular function alone that was prevented when calf muscle
      contractions were performed. Collectively, these data highlight the
      susceptibility of the microcirculation to short periods of inactivity and the
      beneficial role of skeletal muscle contraction for vascular health. ABSTRACT:
      Prolonged sitting for 1-6 h has been shown to impair leg macrovascular [i.e.
      reduced flow-mediated dilatation (FMD)] and microvascular (i.e. reduced reactive
      hyperaemia) function. These impairments appear to be mediated through reductions
      in shear stress. Interestingly, a reduction in shear rate has been observed as
      early as 10 min into sitting. However, it is unknown whether this acute reduction
      in shear stress is sufficient to affect vascular function. Accordingly, we
      studied 18 young men and assessed popliteal artery FMD and reactive hyperaemia
      before (Baseline) and after (PostSit) a 10 min sitting period. Popliteal artery
      shear rate was significantly reduced during sitting (Baseline, 62 +/- 35 s-1 ; 10
      min sitting, 27 +/- 13 s-1 ; P < 0.001). Macrovascular function was unaffected by
      10 min of sitting (Baseline, 4.4 +/- 2.1%; PostSit, 4.3 +/- 2.3%; P = 0.97), but
      microvascular function was reduced (Baseline, 4852 +/- 2261 a.u.; PostSit, 3522
      +/- 1872 a.u.; P = 0.02). In a subset of individuals, we extended the recovery
      period after sitting and demonstrated that resting shear rate and reactive
      hyperaemia responses remained low up to 1 h post-sitting (P < 0.001), whereas FMD
      was unchanged throughout (P = 0.99). Additionally, time control experiments were
      performed with participants in an immobile supine position, which demonstrated no
      change in macrovascular function (P = 0.94) but, unexpectedly, a reduction in
      microvascular function (P = 0.008). Importantly, when calf muscle contractions
      were performed during supine rest, reactive hyperaemia responses were maintained
      (P = 0.76), along with FMD (P = 0.88). These findings suggest that the leg
      microcirculation might be more vulnerable to short periods of inactivity, whereas
      conduit artery vasodilatation appears well maintained. Moreover, intermittent
      skeletal muscle contractions are beneficial for microvascular function.

PMID- 30110510
TI  - Distance-independent Cross-correlated Relaxation and Isotropic Chemical Shift
      Modulation in Protein Dynamics Studies.
AB  - Cross-correlated relaxation (CCR) in multiple-quantum coherences differs from
      other relaxation phenomena in its theoretical ability to be mediated across an
      infinite distance. The two interfering relaxation mechanisms may be dipolar
      interactions, chemical shift anisotropies, chemical shift modulations or
      quadrupolar interactions. These properties make multiple-quantum CCR an
      attractive probe for structure and dynamics of biomacromolecules not accessible
      from other measurements. Here, we review the use of multiple-quantum CCR
      measurements in dynamics studies of proteins. We compile a list of all
      experiments proposed for CCR rate measurements, provide an overview of the theory
      with a focus on protein dynamics, and present applications to various protein
      systems.

PMID- 30110511
TI  - In Silico Prediction of Blood-Brain Barrier Permeability of Compounds by Machine
      Learning and Resampling Methods.
AB  - The blood-brain barrier (BBB) as a part of absorption protects the central
      nervous system by separating the brain tissue from the bloodstream. In recent
      years, BBB permeability has become a critical issue in chemical ADMET prediction,
      but almost all models were built using imbalanced data sets, which caused a high
      false-positive rate. Therefore, we tried to solve the problem of biased data sets
      and built a reliable classification model with 2358 compounds. Machine learning
      and resampling methods were used simultaneously for the refinement of models with
      both 2 D molecular descriptors and molecular fingerprints to represent the
      chemicals. Through a series of evaluation, we realized that resampling methods
      such as Synthetic Minority Oversampling Technique (SMOTE) and SMOTE+edited
      nearest neighbor could effectively solve the problem of imbalanced data sets and
      that MACCS fingerprint combined with support vector machine performed the best.
      After the final construction of a consensus model, the overall accuracy rate was
      increased to 0.966 for the final external data set. Also, the accuracy rate of
      the model for the test set was 0.919, with an excellent balanced capacity of
      0.925 (sensitivity) to predict BBB-positive compounds and of 0.899 (specificity)
      to predict BBB-negative compounds. Compared with other BBB classification models,
      our models reduced the rate of false positives and were more robust in prediction
      of BBB-positive as well as BBB-negative compounds, which would be quite helpful
      in early drug discovery.

PMID- 30110512
TI  - Tuning Gas Adsorption by Metal Node Blocking in Photoresponsive Metal-Organic
      Frameworks.
AB  - By combining first-principles calculations and classical molecular simulations,
      an atomistic-level of understanding was provided towards the notable change in
      CO2 adsorption upon light treatment in two recently reported photoactive metal
      organic frameworks, PCN-123 and Cu2 (AzoBPDC)2 (AzoBiPyB). It was demonstrated
      that the reversible decrease in gas adsorption upon isomerization can be
      primarily attributed to the blocking of the strong adsorbing sites at the metal
      nodes by azobenzene molecules in a cis configuration. The same mechanism was
      found to apply also to other molecules, for example, alkanes and toxic gases.
      Such understandings are instrumental to the future design of photoresponsive
      metal-organic frameworks. For example, the metal node-blocking mechanism can be
      leveraged to achieve optimal adsorption properties as a function of metal
      substitution and/or ligand functionalization. As a proof of concept, it was shown
      that the working capacity could be increased by a factor of two in PCN-123 by
      replacing the Zn4 O node with the more strongly adsorbing Mg4 O.

PMID- 30110513
TI  - Unified strategy for HPLC-MS evaluation of bioactive compounds for quality
      control of herbal products.
AB  - Evaluation of safety, quality and composition of herbal products and food
      supplements based on botanical ingredients is a matter of serious concern. For
      screening of botanicals in herbal products multitargeted and group-targeted
      approaches may be applied. In the group-targeted approach botanicals are
      characterized by means of an appropriate group of structurally related biomarkers
      compared with the multitargeted approach where a number of selected analytes are
      monitored based on a multiple reaction monitoring survey. In this study a unified
      strategy for quality control of herbal products was developed on the basis of
      fast ultrasound-assisted extraction, chromatographic separation and mass
      spectrometric quantification of bioactive compounds. A large list of unique
      biomarkers were monitored under almost identical chromatographic conditions,
      while an efficient strategy for HPLC-MS group-targeted analysis was also
      developed for comprehensive evaluation of chemical composition of botanicals
      intensively used for herbal product manufacturing. In the latter case,
      structurally close compounds were determined in a single ion monitoring mode for
      the characteristic group of fragment ions, allowing fast profiling and quality
      assessment of the plant material or complex food supplement. The sensitivity of
      the developed approaches was on the level of 1-50 ng/mL, which is higher than
      that of existing HPLC-UV quality control methods.

PMID- 30110515
TI  - Retrospective radiographic observational study of 1692 Straumann tissue-level
      dental implants over 10 years: I. Implant survival and loss pattern.
AB  - BACKGROUND: Implant dentistry is progressing based on extensive scientific
      results including preclinical and clinical studies. Researchers and clinicians
      have focused on implant designs and surface characteristics, which has resulted
      in various features being developed and introduced for enhancing osseointegration
      and reducing complications. PURPOSE: The purpose of this study was to determine
      the cumulative survival rates of Straumann tissue-level dental implants over a 10
      year period and identify the patterns of implant loss at a single research
      institution. MATERIALS AND METHODS: In total, 1692 implants were installed in 881
      patients who visited the Department of Periodontology, Dental Hospital, Yonsei
      University, Seoul from January 2003 to December 2009. Cases in which the implant
      was completely removed were defined as implant failures. Electronic or paper
      charts and radiographs were used to determine whether the implants failed. The
      survival rate of implants was analyzed using lifetime tables and Kaplan-Meier
      survival estimates. Log-rank test and Cox regression with shared frailty were
      used to analyze the risk factors and the types of implant failure. RESULTS: The
      10-year cumulative survival rates were 98.23% and 95.70% at the implant and
      patient levels, respectively. Before installing a prosthesis (defined as the
      early stage), 13 implants in 10 patients were removed, while eight implants in
      seven patients were removed after completing a prosthesis (defined as the late
      stage). The cumulative survival rate was related to the implant diameter, length,
      site, and insertion torque. Most implant failures within 1 year were attributable
      to osseointegration failure. There were several cases of failure in the late
      stage without apparent marginal bone loss. CONCLUSION: Straumann tissue-level
      dental implants showed low failure rates and can be considered a useful long-term
      treatment option. The length, placement site, and insertion torque might affect
      implant survival.

PMID- 30110516
TI  - Lightning Rods, Earthquakes, and Regional Identities: Towards a Multi-Scale
      Framework of Assessing Fracking Risk Perception.
AB  - Hydraulic fracturing has provided a persistent, polarizing, and highly
      politicized source of controversy internationally and in numerous national
      contexts for just under a decade. This research uses hydraulic fracturing (i.e.,
      fracking) operations in New Zealand as a vignette through which to understand the
      underlying causes of controversy and the appropriateness of attempts to address
      them. A multi-method approach using interviews (n = 25), diagrammatic analysis,
      and newsprint media was applied to evidence two major findings. First, previous
      attempts to explain fracking controversy based on social constructivist theory
      lack a multi-scalar approach to the assessment of factors that influence risk
      perceptions. It is found that risk perception surrounding fracking in New Zealand
      reflects intra-scalar interactions between factors originating at the
      international, national, regional, and local scale. Second, there is a concerning
      absence of critique pertaining to the concept of "social license to operate"
      (SLO), which has been advocated both internationally and nationally as an
      appropriate form of stakeholder engagement. This article contributes to the SLO
      outcomes literature by establishing a need to consider multi-scalar influences on
      risk perception when explaining diverse SLO outcomes in communities where
      fracking operations are prospective or already taking place.

PMID- 30110517
TI  - Recent Advances in Radical-Enabled Bicyclization and Annulation/1,n
      Bifunctionalization Reactions.
AB  - Over the past few years, the development of new radical reactions has gained
      considerable momentum. Most such radical transformations heavily depend on the in
      situ generation of reactive radical species, initiated by oxidants, metal salts,
      visible-light photocatalysis, or electrocatalysis. In this context, numerous
      radical-enabled bicyclization and annulation/1,n-bifunctionalization reactions
      have been developed, thereby providing efficient synthetic strategies for the
      assembly of functionalized cyclic rings that contain both heterocyclic and
      isocyclic skeletons. In this Focus Review, we highlight recent progress in this
      rapidly growing area by presenting a series of catalytic oxidative reactions,
      along with their reaction mechanisms and applications.

PMID- 30110518
TI  - Why Do Countries Regulate Environmental Health Risks Differently? A Theoretical
      Perspective.
AB  - Why do countries regulate, or prefer to regulate, environmental health risks such
      as radiofrequency electromagnetic fields and endocrine disruptors differently? A
      wide variety of theories, models, and frameworks can be used to help answer this
      question, though the resulting answer will strongly depend on the theoretical
      perspective that is applied. In this theoretical review, we will explore eight
      conceptual frameworks, from different areas of science, which will offer eight
      different potential explanations as to why international differences occur in
      environmental health risk management. We are particularly interested in
      frameworks that could shed light on the role of scientific expertise within risk
      management processes. The frameworks included in this review are the Risk
      Assessment Paradigm, research into the roles of experts as policy advisors, the
      Psychometric Paradigm, the Cultural Theory of Risk, participatory approaches to
      risk assessment and risk management, the Advocacy Coalition Framework, the Social
      Amplification of Risk Framework, and Hofstede's Model of National Cultures. We
      drew from our knowledge and experiences regarding a diverse set of academic
      disciplines to pragmatically assemble a multidisciplinary set of frameworks. From
      the ideas and concepts offered by the eight frameworks, we derive pertinent
      questions to be used in further empirical work and we present an overarching
      framework to depict the various links that could be drawn between the frameworks.

PMID- 30110519
TI  - Decline of meadow spittlebugs, a previously abundant insect, along the California
      coast.

PMID- 30110520
TI  - Greater lifetime stress exposure predicts blunted cortisol but heightened DHEA
      responses to acute stress.
AB  - Although prior research has examined how early adversity and chronic stress
      exposure relate to hypothalamic-pituitary-adrenal (HPA) axis responses to acute
      stress, to date, no studies have examined how stressors occurring over the entire
      lifespan predict such responses. To address this issue, we recruited 61 healthy
      young adults and measured their exposure to 55 different types of acute life
      events and chronic difficulties occurring over the lifespan. In addition, we
      characterized differences in participants' HPA axis responses to acute stress by
      measuring their salivary cortisol and DHEA responses to the Trier Social Stress
      Test for Groups. Greater cumulative stress exposure was associated with a blunted
      cortisol response, but a heightened DHEA response, to the acute stressor.
      Moreover, it was participants' exposure to these stressors (i.e., lifetime
      count), not their perceived severity, which predicted their cortisol and DHEA
      responses to acute stress. Furthermore, differential effects were observed by
      stress exposure domain. Notably, only adulthood and marital/partner stressors
      significantly predicted cortisol responses to acute stress, whereas stress was
      more uniformly associated with DHEA responses to the acute stressor. These
      results thus reveal how cumulative stress exposure is associated with HPA axis
      responsivity to acute stress, while highlighting the fact that different
      stressors may have substantially different associations with these biological
      outcomes.

PMID- 30110522
TI  - National Health Center Week - A Celebration of America's Community Health
      Centers.

PMID- 30110521
TI  - Endovascular coiling versus neurosurgical clipping for people with aneurysmal
      subarachnoid haemorrhage.
AB  - BACKGROUND: Around 30% of people who are admitted to hospital with aneurysmal
      subarachnoid haemorrhage (SAH) will rebleed in the initial month after the
      haemorrhage if the aneurysm is not treated. The two most commonly used methods to
      occlude the aneurysm for prevention of rebleeding are microsurgical clipping of
      the neck of the aneurysm and occlusion of the lumen of the aneurysm by means of
      endovascular coiling. This is an update of a systematic review that was
      previously published in 2005. OBJECTIVES: To compare the effects of endovascular
      coiling versus neurosurgical clipping in people with aneurysmal SAH on poor
      outcome, rebleeding, neurological deficit, and treatment complications. SEARCH
      METHODS: We searched the Cochrane Stroke Group Trials Register (March 2018). In
      addition, we searched CENTRAL (2018, Issue 2), MEDLINE (1966 to March 2018),
      Embase (1980 to March 2018), US National Institutes of Health Ongoing Trials
      Register (March 2018), and World Health Organization (WHO) International Clinical
      Trials Registry Platform (ICTRP) (last searched March 2018). We also contacted
      trialists. SELECTION CRITERIA: We included randomised trials comparing
      endovascular coiling with neurosurgical clipping in people with SAH from a
      ruptured aneurysm. DATA COLLECTION AND ANALYSIS: Two review authors independently
      extracted data, and assessed trial quality and risk of bias using the GRADE
      approach. We contacted trialists to obtain missing information. We defined poor
      outcome as death or dependence in daily activities (modified Rankin scale 3 to 6
      or Glasgow Outcome Scale (GOS) 1 to 3). In the special worst-case scenario
      analysis, we assumed all participants in the group with better outcome with
      missing follow-up information had a poor outcome and those in the other group
      with missing data a good outcome. MAIN RESULTS: We included four randomised
      trials involving 2458 participants (range per trial: 20 to 2143 participants).
      Evidence is mostly based on the largest trial. Most participants were in good
      clinical condition and had an aneurysm on the anterior circulation. None of the
      included trials was at low risk of bias in all domains. One trial was at unclear
      risk in one domain, two trials at unclear risk in three domains, and one trial at
      high risk in one domain.After one year of follow-up, 24% of participants
      randomised to endovascular treatment and 32% of participants randomised to the
      surgical treatment group had poor functional outcome. The risk ratio (RR) of poor
      outcome (death or dependency) for endovascular coiling versus neurosurgical
      clipping was 0.77 (95% confidence interval (CI) 0.67 to 0.87; 4 trials, 2429
      participants, moderate-quality evidence), and the absolute risk reduction was 7%
      (95% CI 4% to 11%). In the worst-case scenario analysis for poor outcome, the RR
      for endovascular coiling versus neurosurgical clipping was 0.80 (95% CI 0.71 to
      0.91), and the absolute risk reduction was 6% (95% CI 2% to 10%). The RR of death
      at 12 months was 0.80 (95% CI 0.63 to 1.02; 4 trials, 2429 participants, moderate
      quality evidence). In a subgroup analysis of participants with an anterior
      circulation aneurysm, the RR of poor outcome was 0.78 (95% CI 0.68 to 0.90; 2
      trials, 2157 participants, moderate-quality evidence), and the absolute risk
      decrease was 7% (95% CI 3% to 10%). In subgroup analysis of those with a
      posterior circulation aneurysm, the RR was 0.41 (95% CI 0.19 to 0.92; 2 trials,
      69 participants, low-quality evidence), and the absolute decrease in risk was 27%
      (95% CI 6% to 48%). At five years, 28% of participants randomised to endovascular
      treatment and 32% of participants randomised to surgical treatment had poor
      functional outcome. The RR of poor outcome for endovascular coiling versus
      neurosurgical clipping was 0.87 (95% CI 0.75 to 1.01, 1 trial, 1724 participants,
      low-quality evidence). At 10 years, 35% participants allocated to endovascular
      and 43% participants allocated to surgical treatment had poor functional outcome.
      At 10 years RR of poor outcome for endovascular coiling versus neurosurgical
      clipping was 0.81 (95% CI 0.70 to 0.92; 1 trial, 1316 participants, low-quality
      evidence). The RR of delayed cerebral ischaemia at two to three months for
      endovascular coiling versus neurosurgical clipping was 0.84 (95% CI 0.74 to 0.96;
      4 trials, 2450 participants, moderate-quality evidence). The RR of rebleeding for
      endovascular coiling versus neurosurgical clipping was 1.83 (95% CI 1.04 to 3.23;
      4 trials, 2458 participants, high-quality evidence) at one year, and 2.69 (95% CI
      1.50 to 4.81; 1 trial, 1323 participants, low-quality evidence) at 10 years. The
      RR of complications from intervention for endovascular coiling versus
      neurosurgical clipping was 1.05 (95% CI 0.44 to 2.53; 2 trials, 129 participants,
      low-quality evidence). AUTHORS' CONCLUSIONS: The evidence in this systematic
      review comes mainly from one large trial, and long-term follow-up is available
      only for a subgroup of participants within that trial. For people in good
      clinical condition with ruptured aneurysms of either the anterior or posterior
      circulation the data from randomised trials show that, if the aneurysm is
      considered suitable for both neurosurgical clipping and endovascular coiling,
      coiling is associated with a better outcome. There is no reliable trial evidence
      that can be used directly to guide treatment in people with a poor clinical
      condition.

PMID- 30110523
TI  - An Endoscopic Endonasal Repair of Spontaneous Skull Base Cerebrospinal Fluid
      Leak.
AB  - Idiopathic intracranial hypertension is a disease of elevated intracranial
      pressure that can lead to spontaneous cerebrospinal fluid leak at the skull base.
      We present a case of CSF leak in a young female with undiagnosed idiopathic
      intracranial hypertension that presented as clear rhinorrhea. The defect in the
      skull base was visualized with computerized tomography and repaired
      endoscopically with adjuvant placement of a lumboperitoneal shunt. This case
      outlines the important sequence of repair and postoperative care for spontaneous
      cerebrospinal fluid leak, and demonstrates the safety and efficacy of endoscopic
      endonasal repair.

PMID- 30110524
TI  - Recurrent Ischemic Stroke: A Manifestation of a Sinus of Valsalva Pseudoaneurysm.
AB  - An 83-year-old female presented to the emergency department with bilateral eye
      pain, dizziness, and acute shortness of breath. Her blood pressure (BP) at
      presentation was 184/93 mmHg. She was admitted for hypertensive emergency and her
      symptoms improved with BP control. However, during hospitalization, she developed
      left-sided paresthesia which on investigation was found to be secondary to
      ischemic stroke. She had two previous aortic mechanical valve replacements for
      aortic stenosis. Transthoracic echocardiogram revealed a large pseudoaneurysm of
      the non-coronary sinus of Valsalva that we believe was the cause of her recurrent
      stroke. A sinus of Valsalva pseudoaneurysm is an uncommon complication of aortic
      valve replacement surgery which in turn has been associated with aortic rupture,
      myocardial infarction, and stroke. Our case identifies a situation where sinus of
      Valsalva pseudoaneurysm predisposed our patient to recurrent ischemic strokes and
      this should be kept in mind when evaluating a patient with ischemic stroke.

PMID- 30110525
TI  - Sebaceous Carcinoma in Situ Masquerading Clinically and Histologically as Paget
      Disease of the Breast.
AB  - Sebaceous carcinoma in situ is a poorly understood and ill-defined entity. In
      situ sebaceous carcinoma exhibits a similar location pattern to its invasive
      counterpart in that most commonly has a periorbital distribution. Review of the
      literature found only seven cases of extraocular sebaceous carcinoma in situ. We
      present a unique and challenging case of sebaceous carcinoma in situ masquerading
      both clinically and histologically as Paget's disease of the breast. A 61-year
      old female presented to her dermatologist complaining of a 6 mm erythematous waxy
      papule on her medial right breast. The patient's past medical history was
      significant for Muir-Torre syndrome. Clinically, the differential diagnosis
      included Paget disease of the breast, squamous cell carcinoma, and sebaceous
      carcinoma. A shave biopsy revealed an atypical proliferation of large single
      cells limited to the epidermis infiltrating in a pagetoid pattern, as well as
      cohesive nests of round neoplastic cells with mild nuclear atypia, prominent
      nucleoli, and vacuolated cytoplasm. Histologically, the differential diagnosis
      included Paget's disease of the breast, squamous cell carcinoma in situ, melanoma
      in situ, and sebaceous carcinoma in situ. A battery of immunohistochemical stains
      was performed including CK7, EMA, CAM5.2, CK20, and MART-1. The lesional cells
      were positive for adipophilin, factor XIIIa, CK7, and EMA and were negative for
      CAM5.2, CK20, and MART-1 supporting a diagnosis of sebaceous carcinoma in situ.
      Multiple deeper sections were examined and invasion beyond the epidermis was not
      identified. This case adds to the paucity of information available regarding
      extraocular sebaceous carcinoma in situ and warns clinicians of this potential
      diagnostic pitfall especially in patients with Muir-Torre syndrome.

PMID- 30110526
TI  - Community Health Centers in the Dakotas, 2018.
AB  - Community health centers (CHCs) are a critical component of the healthcare safety
      network. The modern era of CHCs began in the mid-1960s although their origin can
      be traced back as far as the first two decades of the 20th century. Over 24
      million people receive their healthcare in CHCs. North and South Dakota are home
      to nine centers and provided care to nearly 110,000 medical and dental patients
      in 2017. All CHCs use a uniform data set to report annually on demographics,
      scope of practice, and clinical measures to assure that they remain true to their
      original mission to provide quality healthcare to the most vulnerable of our
      population.

PMID- 30110527
TI  - Pediatric Eosinophilic Esophagitis.
AB  - Eosinophilic esophagitis (EoE) is a chronic immune-mediated esophageal
      inflammatory disease that is becoming more widely recognized as a cause of
      feeding difficulties in infants and young children, as well as gastroesophageal
      reflux disease (GERD)-like symptoms, dysphagia, and food impaction in children
      and adolescents. The diagnosis of EoE is clinicopathologic, based on endoscopic,
      histologic, and clinical findings. Patients with suspected eosinophilic
      esophagitis require an endoscopy with biopsies. The diagnosis requires the
      presence of 15 or more intraepithelial eosinophils/HPF in at least one endoscopic
      esophageal mucosal biopsy. Histology will reveal mucosal eosinophilia isolated to
      the esophagus, which does not improve following Proton Pump Inhibitor (PPI)
      trial. Other disorders causing esophageal eosinophilia, such as GERD, celiac
      disease, Crohn's disease, infection, hypereosinophilic syndrome, achalasia, and
      drug hypersensitivity must be ruled out. The goals of treatment should include
      both histologic healing of the esophageal mucosa, as well as resolution of
      clinical symptoms. Treatment options include food elimination diets, topical
      steroids, and/or esophageal dilatation. While the understanding of EoE has
      evolved over the past twenty years, it continues to be a challenging diagnosis
      due to the clinical and histopathologic similarities to GERD. Much remains to be
      studied regarding the underlying pathology, as well as appropriate biomarkers to
      better evaluate response to therapy.

PMID- 30110529
TI  - Hypertension Management in Elderly Patients.

PMID- 30110528
TI  - The Patient as Reformation - Here We Stand Part Three - Legitimate Authority and
      True Reform.
AB  - Healthcare delivery in the U.S is in the midst of a social crisis and demands
      social reform. Physician-reformersmust understand that the roots of this dilemma
      lie in a loss of legitimate authority, as it extends to the patient.Legitimate
      authority in medicine exists when patient-centeredness leads - with self-less
      advocacy that strengthensthe patient bond, radical accountability that restores
      the public trust and extraordinary teamwork thataddresses exploding complexity.
      Absent these, authority is simply an exercise of power. Physician-reformers
      muststand on the ground of patient-centeredness and debate the truth-claims of
      patient-centered reform.

PMID- 30110530
TI  - Quality Focus: Immunization Awareness Striving to Improve Rates.

PMID- 30110531
TI  - Combined Glia Inhibition and Opioid Receptor Agonism Afford Highly Potent
      Analgesics without Tolerance.
AB  - Commonly prescribed opioid analgesics produce tolerance upon chronic use due in
      part to induction of hyperalgesia. Given that two reported bivalent ligands
      (MMG22 and MCC22) produce potent antinociception without tolerance only in
      inflamed mice, we have investigated the possible cellular and receptor targets of
      these ligands. The selective microglia inhibitors, minocycline and SB290157,
      antagonized intrathecal (i.t.) MCC22 antinociception orders of magnitude more
      potently than MMG22, suggesting that MCC22 selectively targets activated
      microglia. The astrocyte toxin, l-alpha-aminoadipic acid antagonized MMG22
      antinociception 126-fold without reducing the potency of MCC22, indicating that
      activated astrocytes are targets of MMG22. MK-801 and Ro25-6981 antagonism of
      MMG22 antinociception, but not MCC22, is consistent with selective inhibition of
      activated NMDAR in astrocytes. The antinociception produced by i.t. MMG22 or
      MCC22 were both antagonized by the selective mu opioid receptor antagonist, beta
      FNA, implicating interaction of these ligands with MOR in spinal afferent
      neurons. MCC22 antinociception was potently blocked by kainate or AMPA ion
      channel antagonists (LY382884; NBQX), in contrast to MMG22. It is concluded that
      i.t. MMG22 and MCC22 produce exceptional antinociception via potent inhibition of
      activated spinal glia, thereby leading to desensitization of spinal neurons and
      enhanced activation of neuronal MOR. Thus, the present study suggests a new
      approach to treatment of chronic inflammatory pain without tolerance through a
      single molecular entity that simultaneously inhibits activated glia and
      stimulates MOR in spinal neurons.

PMID- 30110532
TI  - Investigation of Anti-SOD1 Antibodies Yields New Structural Insight into SOD1
      Misfolding and Surprising Behavior of the Antibodies Themselves.
AB  - Mutations in Cu/Zn-superoxide dismutase (SOD1) gene are linked to 10-20% of
      familial amyotrophic lateral sclerosis (fALS) cases. The mutations cause
      misfolding and self-assembly of SOD1 into toxic oligomers and aggregates,
      resulting in motor neuron degeneration. The molecular mechanisms underlying SOD1
      aggregation and toxicity are unclear. Characterization of misfolded SOD1 is
      particularly challenging because of its metastable nature. Antibodies against
      misfolded SOD1 are useful tools for this purpose, provided their specificity and
      selectivity are well-characterized. Here, we characterized three recently
      introduced antimisfolded SOD1 antibodies and compared them with two commercial,
      antimisfolded SOD1 antibodies raised against the fALS-linked variant G93A-SOD1.
      As controls, we compared the reactivity of these antibodies to two polyclonal
      anti-SOD1 antibodies expected to be insensitive to misfolding. We asked to what
      extent the antibodies could distinguish between WT and variant SOD1 and between
      native and misfolded conformations. WT, G93A-SOD1, or E100K-SOD1 were incubated
      under aggregation-promoting conditions and monitored using thioflavin-T
      fluorescence, electron microscopy, and dot blots. WT and G93A-SOD1 also were
      analyzed using native-PAGE/Western blot. The new antimisfolded SOD1 and the
      commercial antibody B8H10 showed variable reactivity using dot blots but
      generally showed maximum reactivity at the time misfolded SOD1 oligomers were
      expected to be most abundant. In contrast, only B8H10 and the control antibodies
      were reactive in Western blots. Unexpectedly, the polyclonal antibodies showed
      strong preference for the misfolded form of G93A-SOD1 in dot blots. Surprisingly,
      antimisfolded SOD1 antibody C4F6 was specific for the apo form of G93A-SOD1 but
      insensitive to misfolding. Antibody 10C12 showed preference for early misfolded
      structures, whereas 3H1 bound preferentially to late structures. These new
      antibodies allow distinction between putative early- and late-forming
      prefibrillar SOD1 oligomers.

PMID- 30110534
TI  - C-H Activation and Proton Transfer Initiate Alkene Metathesis Activity of the
      Tungsten(IV)-Oxo Complex.
AB  - In alkene metathesis, while group 6 (Mo or W) high-oxidation state alkylidenes
      are accepted to be key reaction intermediates for both homogeneous and
      heterogeneous catalysts, it has been proposed that low valent species in their +4
      oxidation state can serve as precatalysts. However, the activation mechanism for
      these latter species-generating alkylidenes-is still an open question. Here, we
      report the syntheses of tungsten(IV)-oxo bisalkoxide molecular complexes
      stabilized by pyridine ligands, WO(OR)2py3 (R = CMe(CF3)2 (2a), R = Si(O tBu)3
      (2b), and R = C(CF3)3 (2c); py = pyridine), and show that upon activation with
      B(C6F5)3 they display alkene metathesis activities comparable to W(VI)-oxo
      alkylidenes. The initiation mechanism is examined by kinetic, isotope labeling
      and computational studies. Experimental evidence reveals that the presence of an
      allylic CH group in the alkene reactant is crucial for initiating alkene
      metathesis. Deuterium labeling of the allylic C-H group shows a primary kinetic
      isotope effect on the rate of initiation. DFT calculations support the formation
      of an allyl hydride intermediate via activation of the allylic C-H bond and show
      that formation of the metallacyclobutane from the allyl "hydride" involves a
      proton transfer facilitated by the coordination of a Lewis acid (B(C6F5)3) and
      assisted by a Lewis base (pyridine). This proton transfer step is rate
      determining and yields the metathesis active species.

PMID- 30110533
TI  - Structure-Based Design of Novel EphA2 Agonistic Agents with Nanomolar Affinity in
      Vitro and in Cell.
AB  - EphA2 overexpression is invariably associated with poor prognosis and development
      of aggressive metastatic cancers in pancreatic, prostate, lung, ovarian, and
      breast cancers and melanoma. Recent efforts from our laboratories identified a
      number of agonistic peptides targeting the ligand-binding domain of the EphA2
      receptor. The individual agents, however, were still relatively weak in
      affinities (micromolar range) that precluded detailed structural studies on the
      mode of action. Using a systematic optimization of the 12-mer peptide mimetic
      123B9, we were able to first derive an agent that displayed a submicromolar
      affinity for the receptor. This agent enabled cocrystallization with the EphA2
      ligand-binding domain providing for the first time the structural basis for their
      agonistic mechanism of action. In addition, the atomic coordinates of the complex
      enabled rapid iterations of structure-based optimizations that resulted in a
      novel agonistic agent, named 135H11, with a nanomolar affinity for the receptor,
      as demonstrated by in vitro binding assays (isothermal titration calorimetry
      measurements), and a biochemical displacement assay. As we have recently
      demonstrated, the cellular activity of these agents is further increased by
      synthesizing dimeric versions of the compounds. Hence, we report that a dimeric
      version of 135H11 is extremely effective at low nanomolar concentrations to
      induce cellular receptor activation, internalization, and inhibition of cell
      migration in a pancreatic cancer cell line. Given the pivotal role of EphA2 in
      tumor growth, angiogenesis, drug resistance, and metastasis, these agents, and
      the associated structural studies, provide significant advancements in the field
      for the development of novel EphA2-targeting therapeutics or diagnostics.

PMID- 30110535
TI  - Directing Neuronal Outgrowth and Network Formation of Rat Cortical Neurons by
      Cyclic Substrate Stretch.
AB  - Neuronal mechanobiology plays a vital function in brain development and
      homeostasis with an essential role in neuronal maturation, pathfinding, and
      differentiation but is also crucial for understanding brain pathology. In this
      study, we constructed an in vitro system to assess neuronal responses to cyclic
      strain as a mechanical signal. The selected strain amplitudes mimicked
      physiological as well as pathological conditions. By subjecting embryonic
      neuronal cells to cyclic uniaxial strain we could steer the direction of neuronal
      outgrowth perpendicular to strain direction for all applied amplitudes. A long
      term analysis proved maintained growth direction. Moreover, stretched neurons
      showed an enhanced length, growth, and formation of nascent side branches with
      most elevated growth rates subsequent to physiological straining. Application of
      cyclic strain to already formed neurites identified retraction bulbs with
      destabilized microtubule structures as spontaneous responses. Importantly,
      neurons were able to adapt to the mechanical signals without induction of cell
      death and showed a triggered growth behavior when compared to unstretched
      neurons. The data suggest that cyclic strain plays a critical role in neuronal
      development.

PMID- 30110536
TI  - Rational Design of Novel Selective Dual-Target Inhibitors of Acetylcholinesterase
      and Monoamine Oxidase B as Potential Anti-Alzheimer's Disease Agents.
AB  - Multifunctional agents aiming at cholinesterases (ChEs) and monoamine oxidases
      (MAOs) are promising therapy for Alzheimer's disease (AD). Herein, a series of
      novel propargylamine-modified pyrimidinylthiourea derivatives (1-4) were designed
      and synthesized as dual inhibitors of ChEs and MAOs with other functions against
      AD. Most of these derivatives inhibited ChEs and MAOs with IC50 values in the
      micro- or nanomolar ranges. Compound 1c displayed the dual functional profile of
      targeting the AChE (IC50 = 0.032 +/- 0.007 MUM) and MAO-B (IC50 = 2.117 +/- 0.061
      MUM), along with the improved blood-brain barrier (BBB) permeability, antioxidant
      ability, and good copper chelating property in vitro. Animal studies showed that
      compound 1c.HCl could inhibit the cerebral AChE/MAO-B activities and alleviate
      scopolamine-induced cognitive impairment in mice. Combined with good oral
      bioavailability ( F = 45.55%), these findings demonstrated that compound 1c may
      be a potent brain permeable multifunctional candidate for the treatment of AD.

PMID- 30110537
TI  - Phenylboronic Acid Functionalized Adsorbents for Selective and Reversible
      Adsorption of Lactulose from Syrup Mixtures.
AB  - Boronate affinity materials have been widely used for enrichment of cis-diol
      molecules. In this work, phenylboronic acid functionalized adsorbents were
      prepared via a simple and efficient procedure grafting phenylboronic acid groups
      onto amino macroporous resins. Elemental analysis has confirmed the successful
      functionalization of AR-1M and AR-2M with approximately 2.17% and 0.73% weight
      percentage of boron. Comparatively, AR-1M possessed higher lactulose adsorption
      capacity ( qe-Lu, 84.78 +/- 0.95 mg/g dry resin) under neutral conditions (pH =
      7), while the introduced glutaraldehyde spacer arms on AR-2M resulted in
      excellent adsorption selectivity (alpha ~ 23), high adsorption efficiency (pi ~
      22%), and fast adsorption/desorption rate. The purity of lactulose (PuDLu)
      through pH-driven adsorption (pH 7-8) and desorption (pH 1.5) can be effectively
      improved depending on the ratio of lactulose to lactose. When lactulose/lactose
      >= 1:1, PuDLu ~ 95% was achieved. No significant drop in qe-Lu (>90%) was
      observed after ten-consecutive repeats. Results demonstrated that the newly
      developed method may achieve satisfactory performance in lactulose purification.

PMID- 30110538
TI  - Synthesis of Double-Layer Nitrogen-Doped Microporous Hollow Carbon@MoS2/MoO2
      Nanospheres for Supercapacitors.
AB  - In this work, a double-layer nitrogen-doped microporous hollow carbon@MoS2/MoO2
      nanosphere (NCs@MoS2/MoO2) is prepared via a facile method utilizing Mo-mediated
      in situ growth on polyaniline-coated polystyrene spheres and carbonization
      process. Because of its unique structure, the as-obtained NCs@MoS2/MoO2 exhibits
      a high specific capacitance (569 F g-1 at 1 A g-1) and excellent rate performance
      (54.8% capacitance retention) from 1 A g-1 (569 F g-1) to 20 A g-1 (312 F g-1)
      when directly used as a supercapacitor electrode. In a two-electrode system, it
      exhibits 81% capacitance retention and 91.4% Coulombic efficiency even after 5000
      cycles at 5 A g-1. Therefore, the prepared NCs@MoS2/MoO2 shows to be an
      outstanding material for supercapacitor electrodes.

PMID- 30110539
TI  - Visible-Light-Triggered Generation of Ultrastable Radical Anion from Nitro
      substituted Perylenediimides.
AB  - An efficient method for visible-light-triggered generation of radicals from mono-
      and dinitro-substituted perylenediimide derivatives is developed. UV-vis-NIR and
      electron paramagnetic resonance measurements were carried out to confirm the
      formation of radicals. Most importantly, these radical anions were remarkably
      stable for several months. Subsequently, the reversible nature of anions was
      validated by both chemical and spectroelectrochemical methods for applications in
      electrochromic materials.

PMID- 30110540
TI  - Structural Dynamics of the PET-Degrading Cutinase-like Enzyme from
      Saccharomonospora viridis AHK190 in Substrate-Bound States Elucidates the Ca2+
      Driven Catalytic Cycle.
AB  - A cutinase-type polyesterase from Saccharomonospora viridis AHK190 (Cut190) has
      been shown to degrade the inner block of polyethylene terephthalate. A unique
      feature of Cut190 is that its function and stability are regulated by Ca2+
      binding. Our previous crystal structure analysis of Cut190S226P showed that one
      Ca2+ binds to the enzyme, which induces large conformational changes in several
      loop regions to stabilize an open conformation [Miyakawa, T., et al. (2015) Appl.
      Microbiol. Biotechnol. 99, 4297]. In this study, to analyze the substrate
      recognition mechanism of Cut190, we determined the crystal structure of the
      inactive form of a Cut190 mutant, Cut190*S176A, in complex with calcium ions
      and/or substrates. We found that three calcium ions bind to Cut190*S176A, which
      is supported by analysis using native mass spectrometry experiments and 3D
      Reference Interaction Site Model calculations. The complex structures with the
      two substrates, monoethyl succinate and monoethyl adipate (engaged and open
      forms), presumably correspond to the pre- and post-reaction states, as the ester
      bond is close to the active site and pointing outward from the active site,
      respectively, for the two complexes. Ca2+ binding induces the pocket to open,
      enabling the substrate to access the pocket more easily. Molecular dynamics
      simulations suggest that a post-reaction state in the engaged form presumably
      exists between the experimentally observed forms, indicating that the substrate
      would be cleaved in the engaged form and then requires the enzyme to change to
      the open form to release the product, a process that Ca2+ can greatly accelerate.

PMID- 30110541
TI  - Stabilizing Oil-in-Water Emulsion with Amorphous and Granular Octenyl Succinic
      Anhydride Modified Starches.
AB  - The effects of pre-gelatinization on the capacity of amorphous and granular
      octenyl succinic anhydride (OSA) starches as an emulsifier were compared. The
      full loss of the granular structure after gelatinization were confirmed by X-ray
      scattering measurements. The particle size of the emulsions prepared by granular
      starches with the degree of substitution of 0.021 and 0.045 was 717.8 and 391.5
      nm, respectively, whereas it was only 307.2 and 283.9 nm of the amorphous OSA
      starch emulsions, respectively. Furthermore, after 30 days of storage, the
      particle size of granular OSA starch emulsions increased to 910.1 and 520.9 nm,
      respectively. However, this value only increased to 376.6 and 335.2 nm in
      emulsions stabilized with the amorphous OSA starch, respectively. These were
      attributed to an increased interfacial thickness, rate of interfacial adsorption,
      and compact packing on the surface, resulting from the flexible assembly behavior
      of amorphous starch chains compared to granular OSA. In addition, emulsions
      stabilized via amorphous OSA starches displayed a higher elastic moduli,
      indicating a greater number of interactions between starch chains and adjacent
      droplets.

PMID- 30110542
TI  - Two-Dimensional versus Three-Dimensional Self-Assembly of a Series of 5
      Alkoxyisophthalic Acids.
AB  - Physisorbed self-assembled monolayers (SAMs) have been suggested as potential
      models for three-dimensional (3D) crystallization. This work studies the effect
      of altering the chain length of 5-alkoxyisophthalic acid (C nISA) on self
      assembled morphology in both two-dimensional (2D) and 3D to explore the extent
      comparisons can be drawn between dimensions. Previous studies of 5
      alkoxyisophthalic acid at solid-liquid interfaces (2D) reported different
      morphologies for C5ISA and C6ISA-alkoxy chains on the one hand and C10ISA and
      C18ISA on the other. Independently, also in 3D a dependence of morphology on
      chain length has been reported, including an unexpected inclusion of a solvent in
      the 3D morphology of C6ISA, while the previous reports of 2D self-assembly were
      driven only by molecule-molecule and molecule-substrate interactions. However, a
      complete set of data for comparison has been missing. Here, we report scanning
      tunneling microscopy (STM) and molecular dynamics simulations performed for C2ISA
      self-assembled monolayers (SAMs) and STM imaging of C6ISA-C9ISA SAMs, to further
      examine self-assembly behavior in 2D. In 3D, X-ray diffraction analysis of C2ISA
      single crystals was carried out to complete the data set. With a complete set of
      data, it was observed that regardless of the dimension, short-chain-length C
      nISAs formed H-bonding-dominated structures, mid-chain-length C nISAs exhibited
      solvent-dependent morphologies, and long-chain-length C nISAs displayed van der
      Waals-dominated solvent-independent structures. However, the transition point
      among morphologies occurred at different chain lengths in 2D and 3D regardless of
      the dominant interaction. The results of this study inform the design of 2D films
      and guide the application of knowledge from physisorbed SAMs to 3D systems,
      including mixed-dimensional (2D/3D) van der Waals heterostructures.

PMID- 30110543
TI  - Influence of Enantiomeric Inhibitors on the Dynamics of Acetylcholinesterase
      Measured by Elastic Incoherent Neutron Scattering.
AB  - The enzyme acetylcholinesterase (AChE) is essential in humans and animals because
      it catalyzes the breakdown of the nerve-signaling substance acetylcholine. Small
      molecules that inhibit the function of AChE are important for their use as drugs
      in the, for example, symptomatic treatment of Alzheimer's disease. New and
      improved inhibitors are warranted, mainly because of severe side effects of
      current drugs. In the present study, we have investigated if and how two
      enantiomeric inhibitors of AChE influence the overall dynamics of noncovalent
      complexes, using elastic incoherent neutron scattering. A fruitful combination of
      univariate models, including a newly developed non-Gaussian model for atomic
      fluctuations, and multivariate methods (principal component analysis and
      discriminant analysis) was crucial to analyze the fine details of the data. The
      study revealed a small but clear increase in the dynamics of the inhibited enzyme
      compared to that of the noninhibited enzyme and contributed to the fundamental
      knowledge of the mechanisms of AChE-inhibitor binding valuable for the future
      development of inhibitors.

PMID- 30110544
TI  - Adaptive Wetting-Adaptation in Wetting.
AB  - Many surfaces reversibly change their structure and interfacial energy upon being
      in contact with a liquid. Such surfaces adapt to a specific liquid. We propose
      the first order kinetic model to describe dynamic contact angles of such adaptive
      surfaces. The model is general and does not refer to a particular adaptation
      process. The aim of the proposed model is to provide a quantitative description
      of adaptive wetting and to link changes in contact angles to microscopic
      adaptation processes. By introducing exponentially relaxing interfacial energies
      and applying Young's equation locally, we predict a change of advancing and
      receding contact angles depending on the velocity of the contact line. Even for
      perfectly homogeneous and smooth surfaces, a dynamic contact angle hysteresis is
      obtained. As possible adaptations, we discuss changes and reconstruction of
      polymer surfaces or monolayers, diffusion and swelling, adsorption of
      surfactants, replacement of contaminants, reorientation of liquid molecules, or
      formation of an electric double layer.

PMID- 30110545
TI  - Polar Solvent Induced Lattice Distortion of Cubic CsPbI3 Nanocubes and
      Hierarchical Self-Assembly into Orthorhombic Single-Crystalline Nanowires.
AB  - Despite the recent surge of interest in inorganic lead halide perovskite
      nanocrystals, there are still significant gaps in their stability disturbance and
      the understanding of their destabilization, assembly, and growth processes. Here,
      we discover that polar solvent molecules can induce the lattice distortion of
      ligand-stabilized cubic CsPbI3, leading to the phase transition into orthorhombic
      phase, which is unfavorable for photovoltaic applications. Such lattice
      distortion triggers the dipole moment on CsPbI3 nanocubes, which subsequently
      initiates the hierarchical self-assembly of CsPbI3 nanocubes into single
      crystalline nanowires. The systematic investigations and in situ monitoring on
      the kinetics of the self-assembly process disclose that the more amount or the
      stronger polarity of solvent can induce the more rapid self-assembly and phase
      transition. These results not only elucidate the destabilization mechanism of
      cubic CsPbI3 nanocrystals, but also open up opportunities to synthesize and store
      cubic CsPbI3 for their practical applications in photovoltaics and
      optoelectronics.

PMID- 30110546
TI  - Noble Gas Inserted Metal Acetylides (Metal = Cu, Ag, Au).
AB  - Metal acetylides (MCCH, M = Cu, Ag, Au) were already experimentally detected in
      molecular form. Herein, we investigate the possibility of noble gas (Ng)
      insertion within the C-H bond of MCCH and their stability is compared with those
      of the reported MNgCCH and HCCNgH molecules. Our coupled-cluster-level
      computations show that MCCNgH (Ng = Kr, Xe, Rn) systems are local minima on the
      corresponding potential energy surfaces, whereas their lighter analogues do not
      remain in the chemically bound form. Further, their stability is analyzed with
      respect to all possible dissociation channels. The most favorable dissociation
      channel leads to the formation of free Ng and MCCH. However, there exists a high
      free energy barrier (29.3-46.9 kcal/mol) to hinder the dissociation. The other
      competitive processes against their stability include two-body and three-body
      neutral dissociation channels, MCCNgH -> MCC + NgH and MCCNgH -> MCC + Ng + H,
      respectively, which are slightly exergonic in nature at 298 K for Ng = Kr, Xe and
      M = Cu, Ag, and for AuCCKrH. However, the Xe analogues for Cu and Ag and AuCCKrH
      would be viable at a lower temperature. AuCCNgH (Ng = Kr-Rn) molecules are the
      best candidates for experimental realization, since they have higher dissociation
      energy values and higher kinetic protection in the case of feasible dissociation
      channels compared to the Cu and Ag systems. A detailed bonding analysis indicates
      that the Ng-H bonds are genuine covalent bonds and there is also a substantial
      covalent character in Ng-C contacts of these molecules. Moreover, the possibility
      of insertion of two Xe atoms in AuCCH resulting in AuXeCCXeH and the stability of
      XeAuXeCCXeH are also tested herein.

PMID- 30110547
TI  - Edge-Limited Valley-Preserved Transport in Quasi-1D Constriction of Bilayer
      Graphene.
AB  - We investigated the quantization of the conductance of quasi-one-dimensional
      (quasi-1D) constrictions in high-mobility bilayer graphene (BLG) with different
      geometrical aspect ratios. Ultrashort (a few tens of nanometers long)
      constrictions were fabricated by applying an under-cut etching technique.
      Conductance was quantized in steps of ~4 e2/ h (~2 e2/ h) in devices with aspect
      ratios smaller (larger) than 1. We argue that scattering at the edges of a quasi
      1D BLG constriction limits the intervalley scattering length, which causes valley
      preserved (valley-broken) quantum transport in devices with aspect ratios smaller
      (larger) than 1. The subband energy levels, analyzed in terms of the bias-voltage
      and temperature dependences of the quantized conductance, indicated that they
      corresponded well to the effective channel width of a physically defined
      conducting channel with a hard-wall confining potential. Our study in ultrashort
      high-mobility BLG nano constrictions with physically tailored edges clearly
      confirms that physical edges are the major source of intervalley scattering in
      graphene in the ballistic limit.

PMID- 30110549
TI  - The Sapphire (0001) Surface: A Transparent and Ultraflat Substrate for DNA
      Nanostructure Imaging.
AB  - Mica is the current substrate of choice for DNA nanostructure imaging, mainly due
      to its atomically flat surface. However, these mica substrates are often not
      optically clear. In this work, sapphire has been evaluated as an alternative
      substrate, with potential to enable parallel optical and AFM studies. Well known
      for its thermal and chemical properties, sapphire is a hard ionic material with
      excellent optical properties. Because sapphire lacks the excellent basal cleavage
      properties of the sheet silicate mica, a process to anneal it at high temperature
      in water vapor was developed to achieve near atomically smooth (average roughness
      = 0.141 nm) terraces. AFM imaging was used to determine the dimensions of these
      terraces and to characterize the morphology of the DNA nanostructures, revealing
      that their structures were preserved, indicating that annealed c-plane cut (0001)
      sapphire is a promising substitute for mica as a flat and transparent substrate
      for DNA nanostructure studies.

PMID- 30110548
TI  - Evaluation of Physicochemical and Antioxidant Properties of Yogurt Enriched by
      Olive Leaf Phenolics within Nanoliposomes.
AB  - Olive leaf extract is a rich source of phenolic compounds and oleuropein which is
      well-known regarding its antioxidant and antimicrobial attributes. However, the
      mentioned phenolic compounds will lose their beneficial properties during storage
      and induce undesirable aftertaste in food products. In this study, olive leaf
      extract-bearing nanoliposomes were produced via the ethanol injection method and
      using phosphatidyl choline plus cholesterol as the reagents for the wall
      material. Later, the prepared nanocarriers were examined in regard to their zeta
      potential, stability, encapsulation efficiency, and particle size. Moreover, the
      prepared nanoliposome-loaded yogurt samples were examined considering syneresis,
      antioxidant activity, pH, acidity, color, and sensorial properties. The mean
      particle size of the fabricated nanoliposomes was in the range of 25-158 nm.
      Also, the entire formulation had a negative charge. The encapsulation efficiency
      was between 70.7 to 88.2%. Besides, the application of nanoliposomes in yogurt
      improved the antioxidant activity, and unlike the yogurt with nonencapsulated
      olive extract, no significant changes in color and sensorial attributes were
      observed and even the syneresis rate was minimized. To conclude, olive leaf
      phenolics can be entrapped within nanoliposomes with a considerable encapsulation
      efficiency for application in food products like yogurt to increase their
      nutritional value and public acceptance.

PMID- 30110550
TI  - NMR Determination of the Binding Constant of Ionic Species: A Caveat.
AB  - Determination of the dissociation constant of ionic complexes with the standard
      NMR titration and NMR dilution techniques may yield a severely compromised
      result, due to the typically unconsidered chemical shift alteration induced by
      the gradual change of the ionic strength during the experiment. We show that the
      reliability of an NMR titration experiment is markedly improved upon keeping the
      overall ionic strength constant.

PMID- 30110551
TI  - Sialic-Acid-Anchored Micelles: A Hierarchical Targeting Device for Enhanced Tumor
      Tissue Accumulation and Cellular Internalization.
AB  - Targeted drug delivery systems (TDDS) have attracted wide attention for their
      reduced drug side effects and improved antitumor efficacy in comparison with
      traditional preparations. While targeting moieties in existing TDDS have
      principally focused on recognition of receptors on the surface of tumor cells,
      accumulation into tumor tissue only could be performed by enhanced permeability
      and retention effects and active transportation into tumor cells. Doxorubicin
      (DOX)-loaded sialic acid-dextran (Dex)-octadecanoic acid (OA) micelles (SA-Dex
      OA/DOX) were designed for targeting hepatocellular carcinoma effectively. The
      synthesized conjugates could self-aggregate to form micelles with a critical
      micelle concentration of 27.6 MUg.mL-1 and diameter of 54.53 +/- 3.23 nm. SA-Dex
      OA micelles incorporated with 4.36% DOX-loading content could prolong in vitro
      drug release to 96 h with 80% of final release. Cellular transportation studies
      revealed that SA-Dex-OA micelles mediated more efficient DOX delivery into Bel
      7402 cells than those without SA modification. In vivo biodistribution testing
      demonstrated that SA-Dex-OA/ICG micelles showed 3.05-fold higher accumulation
      into Bel-7402 tumors. The recognition of overexpressed E-selectin in inflammatory
      tumor vascular endothelial cells led to a large accumulation of SA-Dex-OA/ICG
      micelles into tumor tissue, and the E-selectin upregulated on the surface of
      tumor cells contributed to active cellular transportation into tumor cells.
      Accordingly, SA-Dex-OA/DOX exhibited prior suppression of Bel-7402 tumor growth
      greater than that of Dex-OA/DOX micelles and free DOX (the tumor inhibition:
      79.2% vs 61.0 and 51.3%). These results suggest that SA-functionalized micelles
      with dual targeting properties have high potential for liver cancer therapy.

PMID- 30110552
TI  - Absolute Quantification of ppGpp and pppGpp by Double-Spike Isotope Dilution Ion
      Chromatography-High-Resolution Mass Spectrometry.
AB  - Guanosine 5'-diphosphate 3'-diphosphate (ppGpp) and guanosine 5'-triphosphate 3'
      diphosphate (pppGpp) play a central role in the adaptation of bacterial and plant
      cells to nutritional and environmental stresses and in bacterial resistance to
      antibiotics. These compounds have historically been detected and quantified by
      two-dimensional thin-layer chromatography of 32P-radiolabeled nucleotides. We
      report a new method to quantify ppGpp and pppGpp in complex biochemical matrix
      using ion chromatography coupled to high-resolution mass spectrometry. The method
      is based on isotopic dilution mass spectrometry (IDMS) using 13C to accurately
      quantify the nucleotides. However, the loss of a phosphate group from pppGpp
      during the sample preparation process results in the erroneous quantification of
      ppGpp. This bias was corrected by adding an extra 15N isotope dilution dimension.
      This double-spike IDMS method was applied to quantify the ppGpp and pppGpp in
      Escherichia coli and in a mutant strain deleted for gppA (encoding the ppGpp
      phosphohydrolase) before and after exposure of both strains to serine
      hydroxamate, known to trigger the accumulation of these nucleotides.

PMID- 30110553
TI  - Optimizing the Toehold Strategy of On-Chip Nucleic Acid Hybridization Probe for
      the Discrimination of Single Nucleotide Polymorphism.
AB  - The synthetic DNA hybridization probe has proved its importance in biology and
      biotechnology. In this study, taking advantage of a novel analytical technique
      called dual polarization interferometry (DPI), the influence of the toehold
      strategy of on-chip DNA hybridization probe on the discrimination of single
      nucleotide polymorphism (SNP) was investigated. Through adjusting the toehold
      length, the toehold strategies of on-chip toehold exchange probe were thoroughly
      optimized. For the "6/5" probe, an optimal discrimination factor of 78% against
      the spurious target was achieved. Moreover, the ability of the on-chip probe in
      SNP discrimination was significantly enhanced compared to its pure solution
      counterpart. This simple and rapid detection method for SNP discrimination based
      on the on-chip toehold exchange probe will show great potential in disease
      diagnosis.

PMID- 30110554
TI  - Liver-Targeted Co-delivery of Entecavir and Glycyrrhetinic Acid Based on Albumin
      Nanoparticle To Enhance the Accumulation of Entecavir.
AB  - Hepatitis B, one of the most common contagious viral hepatitis with high
      infection rate, is challenging to treat. Although the treatment for hepatitis B
      has been improved over the years, many therapeutic drugs still have either severe
      adverse effects or insufficient effectiveness via systemic administration. In
      this study, we confirmed that glycyrrhetinic acid can enhance the accumulation of
      entecavir in HepaRG cell and liver. Then we constructed a novel albumin
      nanoparticle co-loading entecavir and glycyrrhetinic acid (ETV-GA-AN) to improve
      liver accumulation of entecavir and investigated its ability to deliver both
      drugs to liver. In vitro cellular uptake study and in vivo tissue distribution
      experiment showed that these negatively charged ETV-GA-AN (112 +/- 2 nm in
      diameter) can increase the accumulation of entecavir in hepatic HepaRG cells and
      improve entecavir distribution in liver. We also revealed the mechanism that
      glycyrrhetinic acid enhances intracellular accumulation of entecavir by
      inhibiting the activity of specific efflux transporters. Our delivery system is
      the first liver-targeted albumin nanoparticle that utilizes the site-specific co
      delivery strategy to delivery entecavir and glycyrrhetinic acid. As it combines
      high efficiency and low toxicity, it possess great potential for treating
      hepatitis B.

PMID- 30110556
TI  - Principles of Ubiquitin-Dependent Signaling.
AB  - Ubiquitylation is an essential posttranslational modification that controls cell
      division, differentiation, and survival in all eukaryotes. By combining multiple
      E3 ligases (writers), ubiquitin-binding effectors (readers), and de-ubiquitylases
      (erasers) with functionally distinct ubiquitylation tags, the ubiquitin system
      constitutes a powerful signaling network that is employed in similar ways from
      yeast to humans. Here, we discuss conserved principles of ubiquitin-dependent
      signaling that illustrate how this posttranslational modification shapes
      intracellular signaling networks to establish robust development and homeostasis
      throughout the eukaryotic kingdom.

PMID- 30110555
TI  - Frontier and remote paramedicine practitioner models.
AB  - INTRODUCTION: For the past 50 years paramedic services and paramedic roles in
      high-income nations have evolved in response to changes in community needs and
      expectations. The aim of this article is to review paramedic models of service
      delivery, with an emphasis on models that have the potential to improve the
      health and wellbeing of frontier and remote populations. METHODS: Paramedic
      models of relevance to rural and frontier settings were identified from searches
      of CINHAL and Medline, while key paramedic-specific journals were individualy
      searched in the event that they were not indexed. Search terms were ambulance,
      paramedic and EMS. These were then combined with model* and rural, remote and
      frontier. These findings were then synthesised. RESULTS: During the 1950s and
      1960s the volunteer transport model, based on the values of community informed
      self-determination, developed to meet local needs for transport to local
      hospitals and medical services. Somewhat later, the technological model,
      characterised by professionally staffed and managed paramedic systems providing
      prehospital using advanced technology and technically skilled staff, became the
      dominant model in metropolitan and regional settings. Paramedic practitioner
      models are now emerging that are part of integrated prehospital systems. These
      provide a range of services to prevent injury and illness, respond to emergencies
      and facilitate recovery, and contribute to efforts to produce a healthy
      community. CONCLUSIONS: Implementation of paramedic practitioner models in
      frontier and remote settings raises challenging policy and practice issues,
      including changes in scopes of practice, design of education programs, self
      regulation of paramedics, and reimbursement.

PMID- 30110557
TI  - Sortase A: A Model for Transpeptidation and Its Biological Applications.
AB  - Molecular biologists and chemists alike have long sought to modify proteins with
      substituents that cannot be installed by standard or even advanced genetic
      approaches. We here describe the use of transpeptidases to achieve these goals.
      Living systems encode a variety of transpeptidases and peptide ligases that allow
      for the enzyme-catalyzed formation of peptide bonds, and protein engineers have
      used directed evolution to enhance these enzymes for biological applications. We
      focus primarily on the transpeptidase sortase A, which has become popular over
      the past few years for its ability to perform a remarkably wide variety of
      protein modifications, both in vitro and in living cells.

PMID- 30110558
TI  - Trafficking of Adhesion and Growth Factor Receptors and Their Effector Kinases.
AB  - Cell adhesion to macromolecules in the microenvironment is essential for the
      development and maintenance of tissues, and its dysregulation can lead to a range
      of disease states, including inflammation, fibrosis, and cancer. The
      biomechanical and biochemical mechanisms that mediate cell adhesion rely on
      signaling by a range of effector proteins, including kinases and associated
      scaffolding proteins. The intracellular trafficking of these must be tightly
      controlled in space and time to enable effective cell adhesion and
      microenvironmental sensing and to integrate cell adhesion with, and
      compartmentalize it from, other cellular processes, such as gene transcription,
      protein degradation, and cell division. Delivery of adhesion receptors and
      signaling proteins from the plasma membrane to unanticipated subcellular locales
      is revealing novel biological functions. Here, we review the expected and
      unexpected trafficking, and sites of activity, of adhesion and growth factor
      receptors and intracellular kinase partners as we begin to appreciate the
      complexity and diversity of their spatial regulation.

PMID- 30110559
TI  - Total Ankle Replacement for Osteoarthritis Following Pilon Fracture of the Tibia.
AB  - BACKGROUND: Outcomes for total ankle replacement (TAR) performed for
      osteoarthritis following pilon fracture are underreported. We compared the
      outcomes between different indications for TAR. METHODS: Patient-reported outcome
      measures (PROMs) for TAR performed from 2006 to 2014 by a single surgeon were
      reviewed. Foot and Ankle Outcome Score (FAOS), SF-36, comorbidities, self
      reported body mass index (BMI), and patient satisfaction scores were reviewed.
      Data were collected preoperatively and at 1 and 2 years postoperatively. Clinical
      notes and radiographs highlighted the indication for TAR. The following subgroups
      were created: osteoarthritis (OA), rheumatoid arthritis (RA), pilon fracture
      (PF), ankle fracture (AF), and posttraumatic arthritis without previous fracture
      (PTOA). PROMs were available for 173 TARs: 89 (51.4%) for OA, 36 (20.8%) for AF,
      21 (12.1%) for RA, 15 (8.7%) for PF, and 12 (6.9%) for PTOA. The pilon fracture
      group were the youngest and had the highest BMI (mean, 56.5 years; mean BMI, 31.6
      kg/m2). No difference was found in number of reported comorbidities ( P > .05).
      RESULTS: Significant improvement in FAOS scores was seen in all subgroups from
      preoperatively to 1 year ( P = .01, .05, and .03). SF-36 had similar results for
      all subgroups with improvement in all parameters by 2 years. Significant
      improvement in role physical and role emotional domains was seen by 1 year
      following TAR ( P = .018 and P = .042). Patient satisfaction scores were similar
      in each group. There was no major difference in any of the reported outcomes
      between subgroups by 2 years postoperatively. CONCLUSION: We found similar
      outcomes for patients who underwent TAR after pilon fracture compared to other
      indications. LEVEL OF EVIDENCE: Level III, comparative study.

PMID- 30110560
TI  - MicroRNA-204-5p suppresses IL6-mediated inflammatory response and chemokine
      generation in HK-2 renal tubular epithelial cells by targeting IL6R.
AB  - During the pathogenetic process of varied kidney diseases, renal tubules are the
      major sites in response to detrimental insults, including pro-inflammatory
      stimuli. MicroRNA-204-5p (miR-204-5p) can be detected in the renal tubular
      epithelial cells in the normal kidney, its expression however is downregulated in
      the kidney with pathological changes. This study aimed to investigate the role of
      miR-204-5p in interleukin 6 (IL6)-mediated inflammatory response and chemokine
      production in HK-2 renal tubular cells. In HK-2 cells, the expression of miR-204
      5p was downregulated in response to exogenous pro-inflammatory stimulus, tumor
      necrosis factor alpha (TNFalpha) or IL1beta, while that of IL6 receptor alpha
      (IL6R) was upregulated. Dual-luciferase results confirmed that miRNA-204-5p
      directly targeted IL6R. In addition to suppressing IL6R expression, miRNA-204-5p
      agomir also inhibited the phosphorylation of signal transducer and activator of
      transcription 3 (STAT3) in HK-2 cells exposed to exogenous IL6. Further, miRNA
      204-5p suppressed the over-production of pro-inflammatory mediators
      (cyclooxygenase 2 and prostaglandin E2) and chemokines (C-C motif chemokine
      ligand 2 and C-X-C motif chemokine ligand 8). The anti-inflammatory effects of
      miRNA-204-5p were attenuated when IL6R was re-expressed in HK-2 cells.
      Collectively, our study reveals that miR-204-5p inhibits the inflammation and
      chemokine generation in renal tubular epithelial cells by modulating IL6/IL6R
      axis.

PMID- 30110561
TI  - Acute decompression following simulated dive conditions alters mitochondrial
      respiration and motility.
AB  - While barotrauma, decompression sickness and drowning-related injuries are common
      morbidities associated with diving and decompression from depth, it remains
      unclear what impact rapid decompression has on mitochondrial function. In vitro
      diving simulation was performed with human dermal fibroblast cells subjected to
      control, air, nitrogen and oxygen dive conditions. With the exception of gas
      mixture, all other related variables including absolute pressure exposure, dive
      and decompression rates, and temperature were held constant. High-resolution
      respirometry was used to examine key respiratory states. Mitochondrial dynamic
      function including net movement, number, and rates of fusion/fission events were
      obtained from fluorescence microscopy imaging. Effects of the dive conditions on
      cell cytoskeleton were assessed by imaging both actin and microtubules.
      Fibroblasts in the Air group had lower Max respiration when compared to both the
      Control and Nitrogen groups. The Oxygen group had overall lower respiration when
      compared to all other groups. All groups demonstrated lower mitochondrial
      motility when compared to the Control group. Rates of fusion and fission events
      were the same between all groups. There were visible differences in cell
      morphology consistent with the actin staining, however there were no appreciable
      changes to the microtubules. This is the first study to directly assess
      mitochondrial respiration and dynamics in a cell model of decompression. Both
      hyperbaric oxygen and air dive conditions produce deleterious effects on overall
      mitochondrial health in fibroblasts.

PMID- 30110562
TI  - Expansion capacity of human muscle progenitor cells differs by age, sex, and
      metabolic fuel preference.
AB  - Activation of satellite cells and expansion of the muscle progenitor cell (MPC)
      population is essential to generate a sufficient number of cells to repair
      damaged skeletal muscle. Proliferating MPCs have high energetic and biosynthetic
      material requirements, and the ability to utilize oxidative phosphorylation
      (OXPHOS) and/or glycolysis may affect expansion capacity of MPCs. In the present
      study, we investigated whether donor age and sex impact human MPC (hMPCs)
      expansion capacity and metabolic fuel preference. hMPCs from young and old males
      and females were grown for 408 h (17 days). Percent confluency, live nuclei
      count, and dead cell count were measured every 24 h. Metabolic phenotype was
      assessed using glucose uptake, expression of genes related to glycolysis and
      OXPHOS, and the Seahorse XF24 Phenotype Test Kit during the exponential phase of
      growth. hMPCs from old male donors had impaired expansion capacity secondary to
      heightened cell death early in expansion compared to hMPCs from young male
      donors, an effect not observed in female hMPCs. Age-related differences in
      metabolism were also sex-dependent; markers of OXPHOS were altered in old (vs.
      young) male hMPCs while markers of metabolism were largely unaffected by age in
      female hMPCs. For the first time, we identify sex-specific differences in cell
      death and OXPHOS that contribute to altered expansion capacity of hMPC cell
      populations with age.

PMID- 30110563
TI  - Pathophysiology of stroke: the many and varied contributions of brain
      microvasculature.

PMID- 30110564
TI  - Hydrogen sulfide alleviates hyperhomocysteinemia-mediated skeletal muscle atrophy
      via mitigation of oxidative and endoplasmic reticulum stress injury.
AB  - Although hyperhomocysteinemia (HHcy) occurs due to the deficiency in
      cystathionine-beta-synthase (CBS) causing skeletal muscle dysfunction, it is
      still unclear whether this effect is mediated through oxidative/endoplasmic
      reticulum (ER)-stress or both. Nevertheless, there is no treatment option
      available to improve HHcy-mediated muscle injury. Hydrogen sulfide (H2S) is an
      anti-oxidant compound and patients with CBS mutation do not produce H2S. In this
      study, we hypothesized that H2S mitigates HHcy-induced redox imbalance/ER-stress
      during skeletal muscle atrophy via JNK-phosphorylation. We used CBS+/- mice to
      study HHcy-mediated muscle atrophy and treated them with sodium hydrogen sulfide
      (NaHS, an H2S donor). Proteins and mRNAs were examined by Western blots and qPCR.
      Pro-inflammatory cytokines were also measured. Muscle mass and strength were
      studied via fatigue-susceptibility test. Our data revealed that HHcy was
      detrimental to skeletal mass, particularly gastrocnemius and quadriceps muscles
      weights. We noticed that oxidative-stress were reversed by NaHS in Hcy-treated
      C2C12 cells. Interestingly, ER-stress markers (GRP78, ATF6, pIRE1alpha, and pJNK)
      were elevated in-vivo and in-vitro, and NaHS mitigated these effects.
      Additionally, we observed that JNK-phosphorylation was upregulated in C2C12 after
      Hcy treatment, but NaHS could not reduce this effect. Furthermore, inflammatory
      cytokines IL-6 and TNF-alpha were higher in plasma from CBS+/- as compared to
      wild-type mice. FOXO1-mediated Atrogin-1 and MuRF-1 upregulation were attenuated
      by NaHS. Functional studies revealed that NaHS administration improved muscle
      fatigability in CBS+/- mice. In conclusion, our work provides evidence that NaHS
      is beneficial in mitigating HHcy-mediated skeletal injury incited by oxidative/ER
      stress responses.

PMID- 30110565
TI  - Epigenetic modification of intestinal smooth muscle cell phenotype during
      proliferation.
AB  - Inflammation causes proliferation of intestinal smooth muscle cells (ISMC), which
      contributes to a thickened intestinal wall, and also to stricture formation in
      Crohn's disease. Proliferation of ISMC both in vitro and in vivo caused decreased
      expression of marker proteins, but the underlying cause is unclear. Since
      epigenetic change is important in other systems, we examined this in cell lines
      from rat colon at either low passage or after extended growth, using
      immunocytochemistry, immunoblotting and qPCR to evaluate phenotype. Exposure to
      the HDAC inhibitor trichostatin A or 5-azacytidine, a DNMT inhibitor, reversed
      the characteristic loss of phenotypic markers among high passage cell lines of
      ISMC. Expression of smooth muscle actin and SM-22 were markedly increased, as
      well as functional expression of the neurotrophin GDNF. Increased expression of
      muscarinic receptor-3 and MLCK was correlated with an upregulated response to
      cholinergic stimulation. In human ISMC (hISMC) lines from terminal ileum,
      phenotype was similarly affected by extended proliferation. However, hISMC from
      resected Crohn's strictures at low passage already displayed a significantly
      reduced contractile phenotype, compared with patient-matched intrinsic controls,
      and was associated with increased, patient-specific expression of DNMT1, HDAC2,
      and HDAC5. Therefore, protracted growth causes epigenetic alterations that
      account for an altered phenotype of ISMC. A similar process may promote stricture
      formation in Crohn's disease, where the potential for halting progression or even
      reversal of disease through control of phenotypic modulation may become a novel
      treatment option.

PMID- 30110566
TI  - Absence of renal hypoxia in the subacute phase of severe renal ischemia
      reperfusion injury.
AB  - Tissue hypoxia has been proposed as an important event in renal ischemia
      reperfusion injury (IRI) particularly during the period of ischemia and in the
      immediate hours following reperfusion. However, little is known about renal
      oxygenation during the subacute phase of IRI. We employed four different methods
      to assess the temporal and spatial changes in tissue oxygenation during the
      subacute phase (24 h and 5 days after reperfusion) of a severe form of renal IRI
      in rats. We hypothesized that the kidney is hypoxic 24 h and 5 days after an hour
      of bilateral renal ischemia, driven by a disturbed balance between renal oxygen
      delivery (DO2) and oxygen consumption (VO2). Renal DO2 was not significantly
      reduced in the subacute phase of IRI. In contrast, renal VO2 was 55% less 24 h,
      and 49% less 5 days after reperfusion than after sham-ischemia. Inner medullary
      tissue PO2, measured by radiotelemetry was 25 {plus minus} 12% greater 24 h after
      ischemia than after sham-ischemia. By 5 days after reperfusion, tissue PO2 was
      similar to that in rats subjected to sham-ischemia. Tissue PO2 measured by Clark
      electrode was consistently greater 24 h, but not 5 days, after ischemia than
      after sham-ischemia. Cellular hypoxia, assessed by pimonidazole adduct
      immunohistochemistry, was largely absent at both time-points and tissue levels of
      hypoxia inducible factors were downregulated following renal ischemia. Thus, in
      this model of severe IRI, tissue hypoxia does not appear to be an obligatory
      event during the subacute phase, likely due to the markedly reduced oxygen
      consumption.

PMID- 30110567
TI  - MAGI-2 and scaffold proteins in glomerulopathy.
AB  - In many cells and tissues including the glomerular filtration barrier (GFB),
      scaffold proteins are critical in optimizing signal transduction by enhancing
      structural stability and functionality of their ligands. Recently, mutations in
      scaffold protein Membrane-Associated Guanylate Kinase Inverted 2 (MAGI-2)
      encoding gene were identified among the etiology of steroid-resistant nephrotic
      syndrome (SRNS). MAGI-2 interacts with core proteins of multiple pathways such as
      TGF-beta signaling, planar cell polarity pathway, and Wnt/beta-catenin signaling
      in podocyte and slit diaphragm. Through the interaction with its ligand, MAGI-2
      modulates the regulation of apoptosis, cytoskeletal reorganization, and
      glomerular development. This review aims to summarize recent findings on the role
      of MAGI-2 and some other scaffold proteins such as nephrin and synaptopodin in
      the underlying mechanisms of glomerulopathy.

PMID- 30110568
TI  - GLP-1 Receptor Agonists in Diabetic Kidney Disease: from the Patient-Side to the
      Bench-Side.
AB  - Diabetic kidney disease (DKD), one of the most common and severe microvascular
      complications of diabetes, is the leading cause of chronic kidney disease and end
      stage kidney disease worldwide. Since the development of renin-angiotensin system
      inhibition nearly three decades ago, no new therapeutic agents have received
      regulatory approval for treatment of DKD. Glucagon like peptide-1 (GLP-1)
      receptor agonists, a class of newer anti-hyperglycemic agents, have shown promise
      for prevention of DKD onset and progression. This perspective summarizes clinical
      and experimental observations to give insight into biological mechanisms beyond
      glycemic control, such as natriuresis and anti-inflammatory actions, for
      preservation of kidney function in patients with diabetes.

PMID- 30110569
TI  - Kidney Injury Molecule-1 Identifies Antemortem Injury in Postmortem Adult and
      Fetal Kidney.
AB  - There is currently no technique to unambiguously diagnose antemortem kidney
      injury on postmortem examination since postmortem tissue damage and autolysis are
      common. We assessed the ability to detect kidney injury molecule-1 (KIM-1)
      expression in adult and fetal kidneys examined at autopsy. In adult kidneys (n=52
      subjects), we found that the intensity of KIM-1 staining significantly correlated
      with the antemortem level of serum creatinine, and this was independent of the
      extent of tissue autolysis. Kidneys from a total of 52 fetal/neonatal subjects,
      30 stillborns and 22 liveborns, were assessed for KIM-1 staining. Given that
      serum creatinine is unreliable and often unavailable in fetuses and newborns, we
      assessed pre-terminal hypoxia in fetuses by the presence of squames in pulmonary
      alveoli and by required intubation. KIM-1 expression correlated with these
      clinical indices of hypoxia. The expression of KIM-1 was seen in a majority of
      the fetal and neonatal autopsy kidneys (77%, 40/52) as early as 16 weeks of
      gestation, even in the presence of autolysis. Thus, KIM-1 is a specific and
      stable marker of antemortem tubular injury in adult and fetuses, despite
      postmortem autolysis.

PMID- 30110570
TI  - VESICLES BEARING GIFTS: THE FUNCTIONAL IMPORTANCE OF MICRO-RNA TRANSFER IN
      EXTRACELLULAR VESICLES IN CHRONIC KIDNEY DISEASE.
AB  - Extracellular vesicles (EVs), including microparticles (MPs) and exosomes (EXOs),
      are derived from a wide range of mammalian cells including blood platelets,
      endothelial cells, and kidney cells and can be detected in body fluids including
      blood and urine. While EVs are well established as diagnostic markers under
      pathophysiological and stress conditions, there is also mounting evidence of
      their functional significance as vehicles for communication between cells
      mediated by the presence of nucleic acids, especially microRNAs (miRs),
      encapsulated in the EVs. miRs regulate gene expression, are transported both in
      MPs and EXOs, and exert profound effects in the kidney. Here we review current
      understanding of the links between EVs and miRs, discuss the importance of miRs
      in kidney disease, and shed light on the role of EVs in transferring miRs through
      the circulation between the renal, vascular and inflammatory cell populations
      that are functionally important in patients with CKD.

PMID- 30110571
TI  - Potassium Conservation is Impaired in Mice with Reduced Renal Expression of
      Kir4.1.
AB  - To better understand the role of the inward-rectifying K channel, Kir4.1
      (KCNJ10), in the distal nephron, we initially studied a global Kir4.1 knock out
      mouse (gKO) which demonstrated the hypokalemia and hypomagnesemia seen in
      SeSAME/EAST syndrome and was associated with reduced Na/Cl cotransporter (NCC)
      expression. Lethality by ~3 wks, however, limits the usefulness of this model, so
      we developed a kidney specific Kir4.1 "knock down" mouse (ksKD) using a cadherin
      16 promoter and Cre-loxP methodology. These mice appeared normal and survived to
      adulthood. Kir4.1 protein expression was decreased ~50% vs. WT mice by
      immunoblotting and immunofluorescence showed moderately reduced Kir4.1 staining
      in DCT that was minimal or absent in CNT and CCD. Under control conditions, the
      ksKD mice showed metabolic alkalosis and relative hypercalcemia but were
      normokalemic and mildly hypermagnesemic despite decreased NCC expression. In
      addition, the mice had a severe urinary concentrating defect associated with
      hypernatremia, enlarged kidneys with tubulocystic dilations and reduced aquaporin
      3 expression. On K/Mg-free diet x 1 wk however, ksKD mice showed marked
      hypokalemia (serum K 1.5 +/- 0.1 mEq/L vs. 3.0 +/- 0.1 for WT) which was
      associated with renal K wasting (transtubular K gradient 11.4 +/- 0.8 vs. 1.6 +/-
      0.4 in WT). Phosphorylated-NCC (pNCC) expression increased in WT but not ksKD
      mice on the K/Mg-free diet, suggesting that loss of NCC adaptation underlies the
      hypokalemia. In conclusion, even modest reduction in Kir4.1 expression results in
      impaired K conservation which appears to be mediated by reduced expression of
      activated NCC.

PMID- 30110573
TI  - Why until Just Now? Undiscovered Uniqueness of the Human Glomerulus!

PMID- 30110572
TI  - Superoxide via Sp3 mechanism increases renal renin activity, renal AT1 receptor
      function and blood pressure in rats.
AB  - We tested a hypothesis that superoxide, by inducing Sp3, increases renal renin
      activity, renal AT1 receptor (AT1R) function and blood pressure (BP) in rats.
      Group 1 rats were treated with vehicle, saline. Group 2 rats were treated with
      superoxide dismutase (SOD) inhibitor diethylthiocarbamate (DETC). Group 3 rats
      were treated with DETC and an SOD mimetic, tempol. Group 4 rats were treated with
      tempol only. All 4 groups of rats were treated for 2 weeks, anesthetized and BP
      recorded. Thereafter, diuresis and natriuresis in response to AT1R blocker
      candesartan were determined. Compared to vehicle-rats, BP increased in DETC-rats.
      The increased BP in DETC-rats decreased with tempol. Diuresis and natriuresis in
      response to candesartan increased in controls, which further increased in DETC
      rats and decreased with tempol. A second set of 4 groups of rats underwent the
      same treatment as above, anesthetized and kidneys obtained for biochemical
      studies. The levels of superoxide but not hydrogen peroxide increased while SOD
      activities decreased in the renal cortical tissues of DETC- than vehicle-rats.
      These effects were attenuated with tempol in DETC-rats. Moreover, tissue renin
      activity and abundance of membranous AT1R proteins increased in DETC- than
      vehicle-rats, and decreased with tempol in DETC-rats. Further, the levels of
      lysine-acetylated, but not serine-phosphorylated, Sp3 increased in the nuclei of
      DETC- than vehicle-rats. The increased levels of Sp3 lysine-acetylation decreased
      in DETC-rats with tempol. Taken together, our results suggest that superoxide
      activates renal Sp3 via lysine-acetylation increasing renin activity, AT1R
      function and BP in rats.

PMID- 30110574
TI  - Agency and Motivation in Adulthood and Old Age.
AB  - This review addresses conceptual and empirical research about how individual
      agency and motivation influences development during adulthood and old age. The
      major life-span approaches to individual agency and developmental regulation are
      discussed, with a focus on the motivational theory of life-span development.
      Developmental agency unfolds through action cycles of pursuing long-term goals
      for optimal development. Individuals differ in their capacity to regulate their
      goal engagements effectively within the age-graded structure of opportunities and
      constraints in their life courses. We discuss a set of research examples about
      specific developmental challenges, such as transition to adulthood, biological
      aging, illness, and societal transformation, and show how individuals, as agents
      in their own development, navigate change for better or worse. We conclude with
      suggestions for future research. Expected final online publication date for the
      Annual Review of Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30110575
TI  - Psychobiological Mechanisms of Placebo and Nocebo Effects: Pathways to Improve
      Treatments and Reduce Side Effects.
AB  - Placebo effects constitute a major part of treatment success in medical
      interventions. The nocebo effect also has a major impact, as it accounts for a
      significant proportion of the reported side effects for many treatments.
      Historically, clinical trials have aimed to reduce placebo effects; however,
      currently, there is interest in optimizing placebo effects to improve existing
      treatments and in examining ways to minimize nocebo effects to improve clinical
      outcome. To achieve these aims, a better understanding of the psychological and
      neurobiological mechanisms of the placebo and nocebo response is required. This
      review discusses the impact of the placebo and nocebo response in health care. We
      also examine the mechanisms involved in the placebo and nocebo effects, including
      the central mechanism of expectations. Finally, we examine ways to enhance
      placebo effects and reduce the impact of the nocebo response in clinical practice
      and suggest areas for future research. Expected final online publication date for
      the Annual Review of Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30110576
TI  - The Emotion Process: Event Appraisal and Component Differentiation.
AB  - Much emotion research has focused on the end result of the emotion process,
      categorical emotions, as reported by the protagonist or diagnosed by the
      researcher, with the aim of differentiating these discrete states. In contrast,
      this review concentrates on the emotion process itself by examining how (a)
      elicitation, or the appraisal of events, leads to (b) differentiation, in
      particular, action tendencies accompanied by physiological responses and
      manifested in facial, vocal, and gestural expressions, before (c) conscious
      representation or experience of these changes (feeling) and (d) categorizing and
      labeling these changes according to the semantic profiles of emotion words. The
      review focuses on empirical, particularly experimental, studies from emotion
      research and neighboring domains that contribute to a better understanding of the
      unfolding emotion process and the underlying mechanisms, including the
      interactions among emotion components. Expected final online publication date for
      the Annual Review of Psychology Volume 70 is January 4, 2019. Please see
      http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30110577
TI  - New Cell Cycle Inhibitors Target Aneuploidy in Cancer Therapy.
AB  - Aneuploidy is a hallmark of cancer. Defects in chromosome segregation result in
      aneuploidy. Multiple pathways are engaged in this process, including errors in
      kinetochore-microtubule attachments, supernumerary centrosomes, spindle assembly
      checkpoint (SAC) defects, and chromosome cohesion defects. Although aneuploidy
      provides an adaptation and proliferative advantage in affected cells, excessive
      aneuploidy beyond a critical level can be lethal to cancer cells. Given this,
      enhanced chromosome missegregation is hypothesized to limit survival of aneuploid
      cancer cells, especially when compared to diploid cells. Based on this concept,
      proteins and pathways engaged in chromosome segregation are being exploited as
      candidate therapeutic targets for aneuploid cancers. Agents that induce
      chromosome missegregation and aneuploidy now exist, including SAC inhibitors,
      those that alter centrosome fidelity and others that are under active study in
      preclinical and clinical contexts. This review explores the therapeutic
      potentials of such new agents, including the benefits of combining them with
      other antineoplastic agents. Expected final online publication date for the
      Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019. Please
      see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID- 30110578
TI  - National Coverage Analysis of CAR-T Therapies - Policy, Evidence, and Payment.

PMID- 30110580
TI  - Ibalizumab in Multidrug-Resistant HIV - Accepting Uncertainty.

PMID- 30110581
TI  - Lessons from an Angry Patient.

PMID- 30110579
TI  - Talazoparib in Patients with Advanced Breast Cancer and a Germline BRCA Mutation.
AB  - BACKGROUND: The poly(adenosine diphosphate-ribose) inhibitor talazoparib has
      shown antitumor activity in patients with advanced breast cancer and germline
      mutations in BRCA1 and BRCA2 ( BRCA1/2). METHODS: We conducted a randomized, open
      label, phase 3 trial in which patients with advanced breast cancer and a germline
      BRCA1/2 mutation were assigned, in a 2:1 ratio, to receive talazoparib (1 mg once
      daily) or standard single-agent therapy of the physician's choice (capecitabine,
      eribulin, gemcitabine, or vinorelbine in continuous 21-day cycles). The primary
      end point was progression-free survival, which was assessed by blinded
      independent central review. RESULTS: Of the 431 patients who underwent
      randomization, 287 were assigned to receive talazoparib and 144 were assigned to
      receive standard therapy. Median progression-free survival was significantly
      longer in the talazoparib group than in the standard-therapy group (8.6 months
      vs. 5.6 months; hazard ratio for disease progression or death, 0.54; 95%
      confidence interval [CI], 0.41 to 0.71; P<0.001). The interim median hazard ratio
      for death was 0.76 (95% CI, 0.55 to 1.06; P=0.11 [57% of projected events]). The
      objective response rate was higher in the talazoparib group than in the standard
      therapy group (62.6% vs. 27.2%; odds ratio, 5.0; 95% CI, 2.9 to 8.8; P<0.001).
      Hematologic grade 3-4 adverse events (primarily anemia) occurred in 55% of the
      patients who received talazoparib and in 38% of the patients who received
      standard therapy; nonhematologic grade 3 adverse events occurred in 32% and 38%
      of the patients, respectively. Patient-reported outcomes favored talazoparib;
      significant overall improvements and significant delays in the time to clinically
      meaningful deterioration according to both the global health status-quality-of
      life and breast symptoms scales were observed. CONCLUSIONS: Among patients with
      advanced breast cancer and a germline BRCA1/2 mutation, single-agent talazoparib
      provided a significant benefit over standard chemotherapy with respect to
      progression-free survival. Patient-reported outcomes were superior with
      talazoparib. (Funded by Medivation [Pfizer]; EMBRACA ClinicalTrials.gov number,
      NCT01945775 .).

PMID- 30110582
TI  - Uremic Frost in End-Stage Renal Disease.

PMID- 30110584
TI  - n-3 Fatty Acid Supplementation and Dry Eye Disease.

PMID- 30110583
TI  - Risk Factors, Mortality, and Cardiovascular Outcomes in Patients with Type 2
      Diabetes.
AB  - BACKGROUND: Patients with diabetes are at higher risk for death and
      cardiovascular outcomes than the general population. We investigated whether the
      excess risk of death and cardiovascular events among patients with type 2
      diabetes could be reduced or eliminated. METHODS: In a cohort study, we included
      271,174 patients with type 2 diabetes who were registered in the Swedish National
      Diabetes Register and matched them with 1,355,870 controls on the basis of age,
      sex, and county. We assessed patients with diabetes according to age categories
      and according to the presence of five risk factors (elevated glycated hemoglobin
      level, elevated low-density lipoprotein cholesterol level, albuminuria, smoking,
      and elevated blood pressure). Cox regression was used to study the excess risk of
      outcomes (death, acute myocardial infarction, stroke, and hospitalization for
      heart failure) associated with smoking and the number of variables outside target
      ranges. We also examined the relationship between various risk factors and
      cardiovascular outcomes. RESULTS: The median follow-up among all the study
      participants was 5.7 years, during which 175,345 deaths occurred. Among patients
      with type 2 diabetes, the excess risk of outcomes decreased stepwise for each
      risk-factor variable within the target range. Among patients with diabetes who
      had all five variables within target ranges, the hazard ratio for death from any
      cause, as compared with controls, was 1.06 (95% confidence interval [CI], 1.00 to
      1.12), the hazard ratio for acute myocardial infarction was 0.84 (95% CI, 0.75 to
      0.93), and the hazard ratio for stroke was 0.95 (95% CI, 0.84 to 1.07). The risk
      of hospitalization for heart failure was consistently higher among patients with
      diabetes than among controls (hazard ratio, 1.45; 95% CI, 1.34 to 1.57). In
      patients with type 2 diabetes, a glycated hemoglobin level outside the target
      range was the strongest predictor of stroke and acute myocardial infarction;
      smoking was the strongest predictor of death. CONCLUSIONS: Patients with type 2
      diabetes who had five risk-factor variables within the target ranges appeared to
      have little or no excess risk of death, myocardial infarction, or stroke, as
      compared with the general population. (Funded by the Swedish Association of Local
      Authorities and Regions and others.).

PMID- 30110585
TI  - Esophageal Atresia and Tracheoesophageal Fistula.

PMID- 30110586
TI  - Daratumumab in Primary Effusion Lymphoma.

PMID- 30110587
TI  - Rationale, Opportunities, and Reality of Biosimilar Medications.

PMID- 30110588
TI  - Clinical Course and Management of Hypertrophic Cardiomyopathy.

PMID- 30110589
TI  - Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1.
AB  - BACKGROUND: Ibalizumab, a humanized IgG4 monoclonal antibody, blocks the entry of
      human immunodeficiency virus type 1 (HIV-1) by noncompetitive binding to CD4.
      METHODS: In this single-group, open-label, phase 3 study, we enrolled 40 adults
      with multidrug-resistant (MDR) HIV-1 infection in whom multiple antiretroviral
      therapies had failed. All the patients had a viral load of more than 1000 copies
      of HIV-1 RNA per milliliter. After a 7-day control period in which patients
      continued to receive their current therapy, a loading dose of 2000 mg of
      ibalizumab was infused; the viral load was quantified 7 days later. Through week
      25 of the study, patients received 800 mg of ibalizumab every 14 days, combined
      with an individually optimized background regimen including at least one fully
      active agent. The primary end point was the proportion of patients with a
      decrease in viral load of at least 0.5 log10 copies per milliliter from baseline
      (day 7) to day 14. RESULTS: A total of 31 patients completed the study. The mean
      baseline viral load was 4.5 log10 copies per milliliter, and the mean CD4 count
      was 150 per microliter. Of the 40 patients in the intention-to-treat population,
      33 (83%) had a decrease in viral load of at least 0.5 log10 copies per milliliter
      from baseline (P<0.001 for the comparison with the control period). The mean
      viral-load decrease was 1.1 log10 copies per milliliter. During the control
      period, 1 patient, who received the optimized background regimen prematurely, had
      a decrease in viral load of 0.5 log10 copies per milliliter. At week 25, patients
      who had received ibalizumab plus an optimized background regimen had a mean
      decrease of 1.6 log10 copies per milliliter from baseline; 43% of the patients
      had a viral load of less than 50 copies per milliliter, and 50% had a viral load
      of less than 200 copies per milliliter. Among 10 patients who had virologic
      failure or rebound, in vitro testing identified 9 who had a lower degree of
      susceptibility to ibalizumab than at baseline. The most common adverse event was
      diarrhea (in 20% of patients). Four patients died from causes related to
      underlying illnesses; 1 had a serious adverse event (the immune reconstitution
      inflammatory syndrome) that was deemed to be related to ibalizumab therapy.
      CONCLUSIONS: In patients with MDR HIV-1 infection who had advanced disease and
      limited treatment options, ibalizumab had significant antiviral activity during a
      25-week study. Evidence of the emergence of diminished ibalizumab susceptibility
      was observed in vitro in patients who had virologic failure. (Funded by the
      Orphan Products Clinical Trials Grants Program of the Food and Drug
      Administration and TaiMed Biologics; TMB-301 ClinicalTrials.gov number,
      NCT02475629 .).

PMID- 30110590
TI  - PD-1 Inhibitor Therapy in Adult T-Cell Leukemia-Lymphoma.

PMID- 30110592
TI  - Case 25-2018: A 63-Year-Old Man with Syncope.

PMID- 30110591
TI  - Smoking Cessation, Weight Change, Type 2 Diabetes, and Mortality.
AB  - BACKGROUND: Whether weight gain after smoking cessation attenuates the health
      benefits of quitting is unclear. METHODS: In three cohort studies involving men
      and women in the United States, we identified those who had reported quitting
      smoking and we prospectively assessed changes in smoking status and body weight.
      We estimated risks of type 2 diabetes, death from cardiovascular disease, and
      death from any cause among those who had reported quitting smoking, according to
      weight changes after smoking cessation. RESULTS: The risk of type 2 diabetes was
      higher among recent quitters (2 to 6 years since smoking cessation) than among
      current smokers (hazard ratio, 1.22; 95% confidence interval [CI], 1.12 to 1.32).
      The risk peaked 5 to 7 years after quitting and then gradually decreased. The
      temporary increase in the risk of type 2 diabetes was directly proportional to
      weight gain, and the risk was not increased among quitters without weight gain
      (P<0.001 for interaction). In contrast, quitters did not have a temporary
      increase in mortality, regardless of weight change after quitting. As compared
      with current smokers, the hazard ratios for death from cardiovascular disease
      were 0.69 (95% CI, 0.54 to 0.88) among recent quitters without weight gain, 0.47
      (95% CI, 0.35 to 0.63) among those with weight gain of 0.1 to 5.0 kg, 0.25 (95%
      CI, 0.15 to 0.42) among those with weight gain of 5.1 to 10.0 kg, 0.33 (95% CI,
      0.18 to 0.60) among those with weight gain of more than 10.0 kg, and 0.50 (95%
      CI, 0.46 to 0.55) among longer-term quitters (>6 years since smoking cessation).
      Similar associations were observed for death from any cause. CONCLUSIONS: Smoking
      cessation that was accompanied by substantial weight gain was associated with an
      increased short-term risk of type 2 diabetes but did not mitigate the benefits of
      quitting smoking on reducing cardiovascular and all-cause mortality. (Funded by
      the National Institutes of Health.).

PMID- 30110593
TI  - Heavier but Healthier - Diabetes and Smoking Cessation.

PMID- 30110594
TI  - Improving the Supply and Quality of Deceased-Donor Organs for Transplantation.

PMID- 30110595
TI  - Digesting New Developments in Biosensors.

PMID- 30110596
TI  - Pseudo-"solid pseudopapillary neoplasms" of the testis: in reality Sertoli cell
      tumors.

PMID- 30110598
TI  - Dissecting executive control circuits with neuron types.
AB  - Executive control supports our ability to behave flexibly in accordance with a
      given situation. In order to fully understand how cortical circuits achieve this
      task, we need to determine the intrinsic physiological and connection profiles of
      neuron types and analyze their functional roles during behavior. This article
      introduces current knowledge regarding neuron type classification in the cortex
      and reviews our understanding of how each neuron type is incorporated in the
      functional cortical circuit to implement executive control. Recent work using
      neuron-type specific imaging/recording has begun to reveal significant functional
      organizations of pyramidal neurons and their subtypes depending on the layers and
      long-range projection targets. GABAergic interneurons also make crucial
      contributions to executive control in a subtype-specific manner. Vasoactive
      intestinal peptide (VIP)-positive interneurons are preferentially recruited by
      top-down inputs from higher-order cortical regions and amplify the signals in
      pyramidal neurons by inhibiting other interneuron subtypes. Particularly in the
      prefrontal cortex, one of the hierarchically highest cortices, executive control
      signals are regulated by the VIP neuron-mediated disinhibition and robustly
      maintained through recurrent connections at a long time scale. The differences
      and commonalities in the functional organization between sensory areas and the
      prefrontal cortex are discussed.

PMID- 30110597
TI  - Encapsulating genetically modified Saccharomyces cerevisiae cells in a flow
      through device towards the detection of diclofenac in wastewater.
AB  - Recently it has been proposed to use sensors based on genetically engineered
      reporter cells to perform continuous online water monitoring. Here we describe
      the design, assembly and performance of a novel flow-through device with
      immobilized genetically modified yeast cells that produce a fluorescent protein
      upon stimulation with diclofenac whose intensity is then detected by fluorescence
      microscopy. Although other devices employing immobilized cells for the detection
      of various analytes have already been described before, as novelty our system
      allows safe enclosure of the sensor cells, and thus, to obtain fluorescent
      signals that are not falsified by a loss of cells. Furthermore, the yeast cells
      are prevented from being released into the environment. Despite the safe
      containment, the immobilized reporter cells are accessible to nutrients and
      analytes. They thus have both the ability to grow and respond to the analyte.
      Both in cell culture medium and standardized synthetic wastewater, we are able to
      differentiate between diclofenac concentrations in a range from 10 to 100 MUM. As
      particularly interesting feature, we show that only the biologically active
      fraction of diclofenac is detected. Nowadays, contamination of wastewater with
      diclofenac and other pharmaceutical residues is becoming a severe problem. Our
      investigations may pave the way for an easy-to-use and cost-efficient wastewater
      monitoring method.

PMID- 30110599
TI  - Pathway-based gene-gene interaction network modelling to predict potential
      biomarkers of essential hypertension.
AB  - Essential hypertension (EH) is a major risk factor for cardiovascular disease.
      Despite considerable efforts to elucidate the pathogenesis of EH, there is an
      imperious need for novel indicators of EH. This study aimed to develop a method
      to predict potential biomarkers of EH from the point of view of network. A
      pathway-based gene-gene interaction (GGI) network model was constructed and
      analyzed, containing 116 nodes and 1272 connections. The nodes represented EH
      related genes, and that connections represented their interactions. The network
      showed a small-world property and uneven degree distribution, suggesting that a
      few highly interconnected hubs played a vital role in EH. An inherent hierarchy
      and assortative mixing pattern were also observed in the network. GNAS, GNB3, PF4
      and PPBP showed the highest values of degrees and centrality indices, and were
      chosen as potential biomarkers of EH. A two-mode network model based on the
      potential biomarkers demonstrated that hemostasis and GPCR ligand binding pathway
      were key pathways contributing to EH. Results of this study improve our current
      understanding of the molecular mechanisms driving EH. The selected genes and
      pathways have the potential to be used in the diagnosis and treatment of EH.
      Moreover, the combination of pathway analysis and complex network methodology
      provides a novel strategy for searching new genetic indicators of complex
      diseases.

PMID- 30110600
TI  - Multiple roles of Adenomatous Polyposis Coli gene in Wnt Signalling - a
      Computational Model.
AB  - The Adenomatous Polyposis Coli (APC) gene is a multifunctional gene that plays a
      major role in regulating the Wnt signalling pathway. The Wnt pathway, when
      activated by Wnt signalling molecules, initiates cell division. Mutation of APC
      disrupts the regulation and causes continuous activation of the Wnt pathway even
      in the absence of Wnt signals, thus causing uncontrolled cell proliferation. APC
      regulates the Wnt pathway by controlling the formation of the nuclear complex
      beta-catenin/TCF that initiates the transcription of the Wnt target genes. There
      are at least five mechanisms by which APC can regulate the formation of the beta
      catenin/TCF complex: This paper presents a computational model for the Wnt
      pathway that explicitly includes the above five roles of APC in regulating beta
      catenin/TCF formation. We use this computational model to perform in-silico
      experiments to study the effect of different functional losses of APC on the
      level of beta-catenin/TCF complex. The simulations also demonstrate the different
      outcomes that could be expected when the system is governed by different
      hypotheses.

PMID- 30110601
TI  - Quantification of bacteriuria caused by Hemolysin-positive Escherichia coli in
      human and mouse urine using quantitative polymerase chain reaction (qPCR)
      targeting hlyD.
AB  - Uropathogenic Escherichia coli (UPEC) cause the majority of community-acquired
      urinary tract infections (UTIs). Quantitation of bacteriuria (the number of
      bacteria in urine) is important for diagnostic approaches and in diverse research
      applications. Most UPEC strains express hemolysin, the expression of which has
      been correlated with the severity of UTI in murine models of infection. In this
      study, we sought to develop and optimise a quantitative Polymerase Chain Reaction
      (qPCR) assay for enumeration of hemolysin-positive UPEC in urine. Using
      recombinant plasmid pJET1.2::hlyD, which we termed pGU2470, the sensitivity range
      and linearity of amplification of qPCR was determined using primers and a probe
      targeting hlyD. Whole-cell preparations containing UPEC were quantified for hlyD
      copy number using CT values and compared to standards prepared with a known
      amount of pGU2470. We compared the efficiency of the assay for analysis of human
      and mouse urine because mouse models of human UTI are frequently used for
      investigating UPEC UTI. Urine samples were collected from healthy adults and
      mouse infection assays and used to assess any potential inhibitory effects of
      urine on the qPCR. The linear quantitative range of the qPCR (i.e. sensitivity)
      in detecting UPEC genomes was 103 copies/ml; qPCR-derived estimates of UPEC
      bacteriuria (based on number of genomes detected) were, on average, ten-fold
      higher that culture-based estimates. Finally, the frequencies of positive and
      negative predictions of UPEC in urine using the qPCR were equivalent to colony
      count methods. This assay provides an alternative to culture-based approaches for
      quantitation of UPEC bacteriuria in research studies.

PMID- 30110602
TI  - Fabrication, characterization and biocompatibility of collagen/oxidized
      regenerated cellulose-Ca composite scaffold for carrying Schwann cells.
AB  - Schwann cell (SC) is the primary structural and functional part of the peripheral
      nervous system, and it plays a key role in the repair and regeneration of
      peripheral nerve. In order to develop a suitable scaffold for SC nerve tissue
      engineering, three kinds of scaffolds, including pristine collagen, pure oxidized
      regenerated cellulose-Ca (ORCCa) and collagen/ORC-Ca composite scaffolds, have
      been fabricated for carrying SC in this study. SC is then seeded on the scaffolds
      to form SC-scaffold nerve tissue engineering composites and evaluate their
      biocompatibility. The chemical and physical structure of the scaffolds are
      investigated by FTIR, NMR and SEM. The wettability of the collagen/ORC-Ca
      composite scaffold is close to that of pristine collagen, and the tensile
      strength of the composite scaffold (0.58 MPa) is better than that of pristine
      collagen (0.36 MPa). Cytotoxicity, cell proliferation, cell adhesion and western
      blotting assays are conducted to evaluate the biocompatibility and properties of
      different scaffolds. The results show that the three scaffolds exhibit no
      toxicity, and the proliferation rate of SC on the collagen/ORC-Ca composite
      scaffold is significantly higher than that of the other scaffolds (p < 0.05). The
      number of the adhesion cells on the composite scaffold (244.67 +/- 13.02) is much
      more than that in the pure ORC-Ca group (p < 0.01). Furthermore, the expression
      of N-Cadheri and PMP22 proteins in the collagen/ORC-Ca composite scaffold is
      significantly superior to the other two scaffolds (both p < 0.01). Therefore, it
      could be concluded that the collagen/ORC-Ca composite is a promising candidate as
      a scaffold for carrying SC to form nerve tissue engineering composites in order
      to assist the peripheral nervous in the repair and regeneration.

PMID- 30110603
TI  - Novel electrospun chitosan/polyvinyl alcohol/zinc oxide nanofibrous mats with
      antibacterial and antioxidant properties for diabetic wound healing.
AB  - Non-healing wound is a serious complication of diabetes, associated with
      extremely slow wound closure, and a high rate of infection, resulting in
      amputation or losses of limbs, high health care cost and poor quality of
      patient's life. In the present study, we hypothesized that nanofiber mats
      composed of a combination of chitosan, polyvinyl alcohol (PVA) and Zinc oxide
      (ZnO) could be an effective option for faster healing of diabetic wounds due to
      the wound healing activities of chitosan-PVA nanofibers and antibacterial
      properties of ZnO. Nanofiber mats of chitosan, PVA and ZnO were synthesized using
      electrospinning technique. The developed nanofibrous mats were characterized by
      scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy
      (FTIR), X-ray diffraction (XRD), antibacterial and antioxidant assays as well as
      in vivo wound healing experiments in rabbits. The results revealed that
      chitosan/PVA/ZnO nanofibrous membranes possessed higher antibacterial potential
      against E. coli, P. aeruginosa, B. subtilis and S. aureus compared to
      chitosan/PVA nanofibrous membranes. Moreover, chitosan/PVA/ZnO nanofibrous
      membranes exhibited higher antioxidant potential compared to chitosan/PVA
      nanofibrous mats. The in vivo wound healing studies showed that chitosan/PVA/ZnO
      nanofibrous membranes resulted in accelerated wound healing as compared to
      chitosan/PVA nanofibers. The current study, thus, reveals that chitosan/PVA/ZnO
      electrospun scaffolds could be effectively helpful in dressings for diabetic
      wounds.

PMID- 30110604
TI  - Breastfeeding Support Experiences of Registered Nurses in a Large Children's
      Hospital System.
AB  - OBJECTIVE: To investigate the workplace breastfeeding support experiences of
      registered nurses (RNs) and how these experiences differed by type of unit.
      DESIGN: A cross-sectional descriptive design. SETTING: A large children's
      hospital health system in the Midwestern United States. PARTICIPANTS: Seventy
      eight RNs who were concurrently breastfeeding and working or who had done so
      within the past 12 months. METHODS: The Workplace Breastfeeding Support Scale was
      used to measure the degree of support that breastfeeding RNs experienced at work
      with four subscales: Break Time, Work Place Policy, Technical Support, and
      Environment (total Cronbach's alpha = .87). An invitation with a link to the
      online Workplace Breastfeeding Support Scale and demographic surveys was
      distributed to RNs via the hospital e-mail system. Descriptive statistics and
      analysis of variance were used to characterize support experiences and explore
      unit-based differences in support levels. RESULTS: Of the participants, 35% were
      first-time mothers, and 60% were currently breastfeeding. Overall, participants
      rated their support positively; scores on the Workplace Policy subscale were
      highest, and scores on the Break Time subscale were lowest among the four domains
      of support. Among RNs who had ceased breastfeeding, we found a positive, weak
      correlation between break time support and duration of breastfeeding (r = .34, p
      = .035). No significant differences in support levels were found among nursing
      unit types or inpatient versus outpatient settings. CONCLUSION: Overall,
      breastfeeding support in the workplace was positively rated, and adequate break
      time was positively related to duration of breastfeeding among participants. No
      evidence was found of different support by unit type in this hospital, which
      suggests that support is consistent across unit types. Future research is needed
      to appraise lactation support for nurses and other employees in different types
      of hospitals and geographic areas.

PMID- 30110606
TI  - Orexinergic neurons are involved in the chemosensory control of breathing during
      the dark phase in a Parkinson's disease model.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder characterized by loss of
      dopaminergic neurons in the substantia nigra compacta (SNpc) and the only risk
      factor is aging. We showed that in 6-hydroxydopamine (6-OHDA)-model of PD there
      is a reduction in the neuronal profile within the brainstem ventral respiratory
      column with a decrease in the hypercapnic ventilatory response. Here we tested
      the involvement of orexin cells from the lateral hypothalamus/perifornical area
      (LH/PeF) on breathing in a 6-OHDA PD model. In this model of PD, there is a
      reduction in the total number of orexinergic neurons and in the number of
      orexinergic neurons that project to the RTN, without changing the number of CO2
      activated orexinergic neurons during the dark phase. The ventilation at rest and
      in response to hypercapnia (7% CO2) was assessed in animals that received 6-OHDA
      or vehicle injections into the striatum and saporin anti-Orexin-B or IgG saporin
      into the LH/PeF during the sleep and awake states. The experiments showed a
      reduction of respiratory frequency (fR) at rest during the light phase in PD
      animals only during sleep. During the dark phase, there was an impaired fR
      response to hypercapnia in PD animals with depletion of orexinergic neurons in
      awake and sleeping rats. In conclusion, the degeneration of orexinergic neurons
      in this model of PD can be related to impaired chemoreceptor function in the dark
      phase.

PMID- 30110607
TI  - False positive screen test for mucopolysaccharidoses in healthy female newborns.
AB  - BACKGROUND: In total, 930 urine samples obtained on 2nd and 3rd day from birth
      have been analyzed for the early diagnosis of Mucopolysaccharidoses. METHODS:
      Dimethylmethylene blue (DMB) assay and one-dimensional electrophoresis were
      performed in all urine samples. Agarose gel electrophoresis, before and after
      treatment with chondroitinase ABC and heparinases, was used for a comprehensive
      characterization. RESULTS: Out of 930 urine samples 7 showed anomalous
      electrophoretic pattern; 5 of them had high GAG levels by DMB test. Atypical
      samples (n = 7) were analyzed by agarose gel electrophoresis. After enzymatic
      digestion, some slow bands were still visible. A second urine sample of the above
      7 newborns was analyzed at the age of 1 month, demonstrating both a normal
      pattern and normal GAG levels. Additional urine and vaginal mucus samples from 10
      term neonates with vaginal bleeding showed the same electrophoretic pattern
      observed in the 7 false positive samples. CONCLUSIONS: The altered
      electrophoretic pattern may be due to the presence of glycoproteins and not to
      specific GAGs, due to high levels of maternal hormones exposure during pregnancy.
      To our knowledge, this is the first time maternal estrogen hormones are proposed
      as a likely cause of false-positive urinary glycosaminoglycan screen test in
      healthy newborns.

PMID- 30110608
TI  - Ultrasensitive quantification of cardiac troponin I by a Single Molecule Counting
      method: analytical validation and biological features.
AB  - AIM: To evaluate analytical and biological characteristics of the Singulex
      Clarity(r) cTnI assay, based upon Single Molecule Counting technology. METHODS:
      Assay's analytical sensitivity, precision, linearity, hook effect, cross
      reactivity or interference by endogenous and exogenous substances, stability,
      99th reference percentile [p99th] in EDTA plasma were evaluated in single or
      multi-site studies. RESULTS: Detection limit was 0.12 ng/L. Sensitivity was 0.14
      ng/L at 20% CV (functional sensitivity) and 0.53 ng/L at 10% CV. Imprecision was
      3.16%-10.0% in a multi-lot, single-site study, and 5.5%-12.0% in a single-lot,
      multi-site study; assay was linear from 0.08 to 25,000 ng/L. No hook effect was
      observed; any cross-reactivity/interference exceeded the 10%. Healthy subjects
      were recruited using clinical history, normal NT-proBNP and eGFR (n = 560) or
      plasma creatinine (n = 535) as inclusion criteria. cTnI was detectable in 96.8%
      of healthy subjects. The p99th were 8.01 (eGFR used) and 8.15 ng/L (plasma
      creatinine); both were measured with <=5.7% CV. Median cTnI were significantly
      higher in older and male than in young and female subjects. CONCLUSIONS: The
      Singulex Clarity cTnI assay show analytical features and % detection in healthy
      subjects that improve the corresponding values of most of the existing high
      sensitivity cTnI assays.

PMID- 30110609
TI  - Strong host specialization in fungus genus Strongwellsea (Entomophthorales).
AB  - The genus Strongwellsea (Entomophthorales) has a unique pathobiology. Infected
      adult dipteran hosts develop a large hole in their abdomens, through which
      conidia are actively discharged while the hosts are still alive. We analyzed the
      IST II region of Strongwellsea from 29 infected hosts representing 15 dipteran
      species from Anthomyiidae, Fanniidae, Muscidae, and Scathophagidae. Each genotype
      was found on only one host species or a few closely related host species.
      Strongwellsea genotypes infecting flies from Anthomyiidae represented a
      monophyletic lineage, including the species Strongwellsea castrans, while
      genotypes infecting Muscidae were very diverse and clustered at different places.
      All three host species from Fanniidae were infected with the same Strongwellsea
      genotype, namely the species Strongwellsea magna. It appears that members of the
      genus Strongwellsea are strongly adapted to their host species and have co
      evolved.

PMID- 30110605
TI  - Prenatal alcohol exposure disrupts male adolescent social behavior and oxytocin
      receptor binding in rodents.
AB  - Social behavior deficits resulting from prenatal alcohol exposure (PAE) emerge
      early in life and become more pronounced across development. Maturational changes
      associated with adolescence, including pubertal onset, can have significant
      consequences for social behavior development, making adolescence a unique period
      of increased vulnerability to social behavior dysfunction. Unfortunately, little
      is known about the underlying neurobiology supporting PAE-related social behavior
      impairments, particularly in the context of adolescence, when the transition to a
      more complex social environment may exacerbate existing deficits in social
      behavior function. Here we perform a comprehensive evaluation of social behavior
      development in PAE animals during two different periods in adolescence using
      three separate but related tests of social behavior in increasingly complex
      social contexts: the social interaction test, the social recognition memory test
      (i.e. habituation-dishabituation test), and the social discrimination test.
      Additionally, we investigated the underlying neurobiology of the oxytocin (OT)
      and vasopressin (AVP) systems following PAE, given their well-documented role in
      mediating social behavior. Our results demonstrate that compared to controls,
      early adolescent PAE animals showed impairments on the social recognition memory
      test and increased OT receptor binding in limbic networks, while late adolescent
      PAE animals exhibited impairments on the social discrimination test and increased
      OTR binding in forebrain reward systems. Taken together, these data indicate that
      PAE impairs adolescent social behavior - especially with increasing complexity of
      the social context - and that impairments are associated with altered development
      of the OT but not the AVP system.

PMID- 30110610
TI  - Metabolic and immunological responses of male and female new Zealand GreenshellTM
      mussels (Perna canaliculus) infected with Vibrio sp.
AB  - Massive mortalities due to pathogens are routinely reported in bivalve
      cultivation that have significant economic consequences for the global
      aquaculture industry. However, host-pathogen interactions and infection
      mechanisms that mediate these interactions are poorly understood. In addition,
      gender-specific immunological responses have been reported for some species, but
      the reasons for such differences have not been elucidated. In this study, we used
      a GC/MS-based metabolomics platform and flow cytometry approach to characterize
      metabolic and immunological responses in haemolymph of male and female mussels
      (Perna canaliculus) experimentally infected with Vibrio sp. Sex-based differences
      in immunological responses were identified, with male mussels displaying higher
      mortality, oxidative stress and apoptosis after pathogen exposure. However,
      central metabolic processes appeared to be similar between sexes at 24 h post
      injection with Vibrio sp. DO1. Significant alterations in relative levels of 37
      metabolites were detected between infected and uninfected mussels. These
      metabolites are involved in major perturbations on the host's innate immune
      system. In addition, there were alterations of seven metabolites in profiles of
      mussels sampled on the second day and mussels that survived six days after
      exposure. These metabolites include itaconic acid, isoleucine, phenylalanine,
      creatinine, malonic acid, glutaric acid and hydroxyproline. Among these, itaconic
      acid has the potential to be an important biomarker for Vibrio sp. DO1 infection.
      These findings provide new insights on the mechanistic relationship between a
      bivalve host and a pathogenic bacterium and highlight the need to consider host
      sex as a biological variable in future immunological studies.

PMID- 30110611
TI  - The origin and early evolution of life in chemical composition space.
AB  - Life can be viewed as a localized chemical system that sits in the basin of
      attraction of a metastable dynamical attractor state that remains out of
      equilibrium with the environment. To explore the implications of this conception,
      I introduce an abstract coordinate system, chemical composition (CC Space), which
      summarizes the degree to which chemical systems are out of equilibrium with the
      bulk environment. A system's chemical disequilibrium (CD) is defined to be
      proportional to the Euclidean distance between the composition of a small region
      of physical space, a pixel, and the origin of CC space. Such a model implies that
      new living states arise through chance changes in local chemical concentration
      ("mutations") that cause chemical systems to move in CC space and enter the basin
      of attraction of a life state. The attractor of a life state comprises an
      autocatalytic set of chemicals whose essential ("keystone") species are produced
      at a higher rate than they are lost to the environment by diffusion, such that
      spatial growth of the life state is expected. This framework suggests that new
      life states are most likely to form at the interface between different physical
      phases, where the rate of diffusion of keystone species is tied to the low
      diffusion regime, whereas food and waste products are subject to the more
      diffusive regime. Once life nucleates, for example on a mineral surface, it will
      tend to grow and generate variants as a result of additional mutations that find
      alternative life states. By jumping from life state to life state, systems can
      eventually occupy areas of CC space that are too far out of equilibrium with the
      environment to ever arise in a single mutational step. Furthermore, I propose
      that variation in the capacity of different surface associated life states to
      persist and compete may systematically favor states that have higher chemical
      disequilibrium. The model also suggests a simple and predictable path from
      surface-associated life to cell-like individuation. This dynamical systems
      theoretical framework provides an integrated view of the origin and early
      evolution of life and supports novel empirical approaches.

PMID- 30110612
TI  - Mitochondrial genome characteristics of Somena scintillans (Lepidoptera:
      Erebidae) and comparation with other Noctuoidea insects.
AB  - In this study, mitogenome of Somena scintillans (Lepidoptera: Erebidae) were
      sequenced and compared with other Noctuoidea species. The mitogenome is 15,410
      base pairs in length. All 13 protein-coding genes (PCGs) are initiated by ATN
      codons except cox1 with CGA and all of PCGs terminate with TAA except nad4 with
      TAG. The codons ACG and CGC are absent. All the tRNA genes could be folded into
      the typical cloverleaf secondary structure except the trnS1 which not only loses
      dihydrouridine (DHU) arm but also mutates its anticodon into TCT. In the AT-rich
      region of the mitogenome the motif 'ATAGA' mutates to 'ATATA' and two copies of
      161 bp-tandem repeats and two 'TA' short tandem repeats are founded. Phylogenetic
      analyses showed that S. scintillans is clustered into subfamily Lymatriinae. The
      phylogenetic relationships within Noctuoidea is (((Nolidae + (Euteliidae +
      Noctuidae)) + Erebidae) + Notodontidae).

PMID- 30110613
TI  - Methylation status of the putative Pax6 promoter in olive ridley sea turtle
      embryos with eye defects: An initial approach.
AB  - Normal development involves the interplay of genetic and epigenetic regulatory
      mechanisms. Pax6 is an eye-selector factor responsible for initiating the
      regulatory cascade for the development of the eyes. For the olive ridley sea
      turtle (Lepidochelys olivacea), a threatened species, eye malformations have been
      reported. In order to study the DNA methylation status of the putative promoter
      of the Pax6 gene in embryos with ocular malformations, an exploratory study was
      carried out in which DNA was isolated from embryos with anophthalmia,
      microphthalmia, and cyclopia, as well as from their normal counterparts. The 5'
      flanking region from the Pax6 gene was isolated, showing two CpG islands (CGIs).
      The methylation status of CGIs in malformed embryos was compared with that of
      normal embryos by bisulfite sequencing. Putative transcription factor binding
      sites and regulatory features were identified. Methylation patterns were observed
      in both CpG and non-CpG contexts, and were unique for each malformed embryo; in
      the CpG context, an embryo with cyclopia showed a methylated cytosine upstream
      the CGI-1 not present in other embryos, an embryo with left anophthalmia
      presented two methylated cytosines in the CGI-1, whereas an embryo with left
      anophthalmia and right microphthalmia showed two methylated cytosines in the CGI
      2. Normal embryos did not show methylated cytosines in the CGI-1, but one of them
      showed one methylcytosine in the CGI-2. Methylated transcription factor-binding
      sites may affect Pax6 expression associated to the cellular response to
      environmental compounds and hypoxia, signal transduction, cell cycle, lens
      physiology and development, as well as the transcription rate. Although
      preliminary, these results suggest that embryos with ocular malformations present
      unique DNA methylation patterns in the putative promoter of the Pax6 gene in L.
      olivacea, and probably those subtle, random changes in the methylation status can
      cause (at least in part) the aberrant phenotypes observed in these embryos.

PMID- 30110614
TI  - The molecularly imprinted polymer essentials: curation of anticancer, ophthalmic,
      and projected gene therapy drug delivery systems.
AB  - The development of polymeric materials as drug delivery systems has advanced from
      systems that rely on classical passive targeting to carriers that can sustain the
      precisely controlled release of payloads upon physicochemical triggers in desired
      microenvironment. Molecularly imprinted polymers (MIP), materials designed to
      capture specific molecules based on their molecular shape and charge
      distribution, are attractive candidates for fulfilling these purposes. In
      particular, drug-imprinted polymers coupled with active targeting mechanisms have
      been explored as potential drug delivery systems. In this review, we have curated
      important recent efforts in the development of drug-imprinted polymers in a
      variety of clinical applications, especially oncology and ophthalmology. MIP
      possesses properties that may complement the traditional delivery systems of
      these two disciplines, such as passive enhanced permeability and retention effect
      (EPR) in cancer tumors, and passive drug diffusion in delivering ophthalmic
      therapeutics. Furthermore, the prospects of MIP integration with the emerging
      gene therapies will be discussed.

PMID- 30110615
TI  - Cationic lipids as one-component vaccine adjuvants: A promising alternative to
      alum.
AB  - Effective vaccine formulations consist of several components: an antigen carrier,
      the antigen, a stimulator of cellular immunity such as a Toll-like Receptors
      (TLRs) ligand, and a stimulator of humoral response such as an inflammasome
      activator. Here, we investigated the immunostimulatory and adjuvant properties of
      lipopolyamines, cationic lipids used as gene carriers. We identified new
      lipopolyamines able to activate both TLR2 and TLR4 and showed that lipopolyamines
      interact with TLRs via a mechanism different from the one used by bacterial
      ligands, activating a strong type-I IFN response, pro-inflammatory cytokines and
      IL-1beta secretion. The TLR and inflammasome stimulations, together with the
      antigen carrier properties of lipopolyamines, resulted in both humoral and
      cellular immunity in mice vaccinated against OVA and make lipopolyamines
      promising one-component vaccine adjuvants.

PMID- 30110616
TI  - Intradiscal delivery of celecoxib-loaded microspheres restores intervertebral
      disc integrity in a preclinical canine model.
AB  - Low back pain, related to degeneration of the intervertebral disc (IVD), affects
      millions of people worldwide. Clinical studies using oral cyclooxygenase-2 (COX
      2) inhibitors have shown beneficial effects, although side-effects were reported.
      Therefore, intradiscal delivery of nonsteroidal anti-inflammatory drugs can be an
      alternative treatment strategy to halt degeneration and address IVD-related pain.
      In the present study, the controlled release and biologic potency of celecoxib, a
      selective COX-2 inhibitor, from polyesteramide microspheres was investigated in
      vitro. In addition, safety and efficacy of injection of celecoxib-loaded
      microspheres were evaluated in vivo in a canine IVD degeneration model. In vitro,
      a sustained release of celecoxib was noted for over 28 days resulting in
      sustained inhibition of inflammation, as indicated by decreased prostaglandin E2
      (PGE2) production, and anti-catabolic effects in nucleus pulposus (NP) cells from
      degenerated IVDs on qPCR. In vivo, there was no evidence of adverse effects on
      computed tomography and magnetic resonance imaging or macroscopic evaluation of
      IVDs. Local and sustained delivery of celecoxib prevented progression of IVD
      degeneration corroborated by MRI, histology, and measurement of NP proteoglycan
      content. Furthermore, it seemed to harness inflammation as indicated by decreased
      PGE2 tissue levels and decreased neuronal growth factor immunopositivity,
      providing indirect evidence that local delivery of a COX-2 inhibitor could also
      address pain related to IVD degeneration. In conclusion, intradiscal controlled
      release of celecoxib from polyesteramide microspheres prevented progression of
      IVD degeneration both in vitro and in vivo. Follow-up studies are warranted to
      determine the clinical efficacy of celecoxib-loaded PEAMs in chronic back pain.

PMID- 30110617
TI  - Early embryonic modification of maternal hormones differs systematically among
      embryos of different laying order: A study in birds.
AB  - Vertebrate embryos are exposed to maternal hormones that can profoundly affect
      their later phenotype. Although it is known that the embryo can metabolize these
      maternal hormones, the metabolic outcomes, their quantitative dynamics and timing
      are poorly understood. Moreover, it is unknown whether embryos can adjust their
      metabolic activity to, for example, hormones or other maternal signals. We
      studied the dynamics of maternal steroids in fertilized and unfertilized rock
      pigeon eggs during early incubation. Embryos of this species are naturally
      exposed to different amounts of maternal steroids in the egg according to their
      laying position, which provides a natural context to study differential embryonic
      regulation of the maternal signals. We used mass spectrometric analyses to map
      changes in the androgen and estrogen pathways of conversion. We show that the
      active hormones are heavily metabolized only in fertilized eggs, with a
      corresponding increase in supposedly less potent metabolites already within one
      fourth of total incubation period. Interestingly, the rate of androgen metabolism
      was different between embryos in different laying positions. The results also
      warrant a re-interpretation of the timing of hormone mediated maternal effects
      and the role of the supposedly biologically inactive metabolites. Furthermore,
      the results also provide a potential solution as to how the embryo can prevent
      maternal steroids in the egg from interfering with its sexual differentiation
      processes as we show that the embryo can metabolize most of the maternal steroids
      before sexual differentiation starts.

PMID- 30110618
TI  - Do women want to talk about birth control at the time of a first-trimester
      abortion?
AB  - OBJECTIVE: To investigate if women desire talking to a counselor or physician
      about contraception when seeking first-trimester medical or surgical abortion.
      STUDY DESIGN: We conducted a cross-sectional study by distributing self
      administered anonymous surveys to women at three clinics in Sacramento,
      California; Chicago, Illinois; and Cleveland, Ohio, from October 2014 to February
      2015. Participants completed surveys after registration and before any in-office
      counseling. We asked whether women want to discuss contraception, specific topics
      they want to discuss, reasons why they may not want to talk about contraception
      and whether they want to receive contraception services as part of their abortion
      care. We conducted regression analyses to assess associations between patient
      characteristics and the desire for counseling. RESULTS: Among 3041 eligible
      women, 1959 (64.4%) completed surveys. Overall, 1208 (61.7%) did not want to
      discuss contraception prior to having an abortion, primarily citing that they
      already know which method they want. We found no association between the desire
      to discuss contraception and age, race, planned abortion method, clinic site and
      number of unplanned pregnancies. Among those who desired to talk about
      contraception, subjects preferred to discuss which contraceptive methods are
      easier to use and more effective as compared to previously used methods.
      Regardless of their desire for a discussion about contraception, 1386 (70.8%) of
      subjects wanted to leave the clinic with a specific method, including a long
      acting reversible method [intrauterine device or implant (190, 13.7%)] or other
      hormonal method [pills, patch, ring or injectable (680, 49.1%)]. CONCLUSIONS: The
      majority of women seeking first-trimester abortion do not come to the clinic
      wanting to discuss contraception, most commonly because they have a preferred
      method in mind. IMPLICATIONS: Providers should ask women presenting for abortion
      if they want to discuss contraception and not assume that they need or desire
      such information. Focused discussions, starting with the preferred method if
      known, may better satisfy women's preferences. Providers should account for such
      desires when allocating resources for contraception services during abortion
      care.

PMID- 30110619
TI  - Carcinoembryonic antigen-targeted nanoparticles potentiate the delivery of
      anticancer drugs to colorectal cancer cells.
AB  - Bioengineered functionalized nanoparticles have extensively been proposed in
      recent years to efficiently deliver anti-cancer drugs to the tumour site, by
      targeting the cancer cells and improving the therapeutic efficiency of active
      molecules. In this work, polymeric poly (lactic-co- glycolic)-polyethyleneglycol
      (PLGA-PEG) nanoparticles were produced by nanoprecipitation and loaded with
      paclitaxel, following surface-functionalized with a monoclonal antibody targeting
      the carcinoembryonic antigen (CEA) of intestinal epithelial cells.
      Physicochemical properties, cytotoxicity and targeting ability of the
      nanoparticles against two intestine epithelial carcinoma cell lines, CEA
      expressing Caco-2 clone and non-CEA-expressing SW480, were assessed. Results
      showed successful production of nanoparticles around 200 nm, and close to charge
      neutrality, encapsulating up to 99% of paclitaxel. Functionalized nanoparticles
      were further constructed, demonstrating to be non-cytotoxic against intestinal
      cells. The targeting ability of functionalized nanoparticles to Caco-2 CEA
      expressing cells was confirmed by flow cytometry, in opposite to SW480 cells.
      Overall, the surface-modified PLGA-PEG nanoparticles with the CEA-targeting
      antibody were successfully developed as nanocarriers for paclitaxel and
      interacted with CEA expressing cells. This specific interaction provide these
      particles ability to be used as targeted systems for colorectal cancer
      therapeutics.

PMID- 30110621
TI  - Residence time distribution of a continuously-operated capsule filling machine:
      Development of a measurement technique and comparison of three volume-reducing
      inserts.
AB  - This paper presents the measurement and analysis of the residence time
      distribution (RTD) of a tamping-pin capsule filling machine. The tamping speed
      and the amount of material inside the powder bowl proved to have a significant
      effect on the RTD. Various inserts into the powder bowl that reduce the volume
      and alter mixing and transport in the bowl were experimentally investigated. To
      obtain the RTD, a tracer-based measurement method was applied and a sophisticated
      data processing strategy was developed. The tracer-based method also allowed
      investigations of stagnant zones in the powder bowl, another important aspect in
      continuous manufacturing (CM). The suitability of tracer material was assessed
      based on a detailed characterization of bulk and tracer material. Characteristic
      parameters of the RTD were extracted and compared, proposing a systematic
      strategy for selection of a suitable insert.

PMID- 30110620
TI  - Identification of molecular-interaction sites between lowly hydrolyzed polyvinyl
      alcohols and indomethacin by NMR spectroscopy.
AB  - To evaluate the potency of hydrolyzed polyvinyl alcohols (PVAs) as matrices for
      solid dispersion (SD) formulations, we examined their inhibitory effects on
      precipitation of a poorly water-soluble drug, indomethacin (IND). Additionally,
      to clarify their mechanism, we investigated the intermolecular interaction of IND
      with PVAs in the supersaturated aqueous solution of IND. In the present study, we
      used five kinds of PVAs, i.e. JR-05 (70.0-74.0% hydrolyzed), JL-05E (80.0-84.0%
      hydrolyzed), JP-05 (87.0-89.0% hydrolyzed), JT-05 (93.5-94.5% hydrolyzed) and JF
      05 (98.0-99.0% hydrolyzed). Of various PVAs, the lowly hydrolyzed PVAs such as JR
      05 and JL-05E dramatically inhibited the precipitate formation of IND.
      Interestingly, the lowly hydrolyzed PVAs possessed micelle-forming ability, and
      inhibited the nucleation and crystal growth of IND. Moreover, strong hydrophobic
      interactions between vinyl acetate unit of lowly hydrolyzed PVA and hydrophobic
      moiety of IND were suggested based on the results of nuclear magnetic resonance
      (1H NMR) and nuclear overhauser effect spectroscopy (NOESY) in deuterium oxide.
      To the best of our knowledge, this is the first report describing the inhibitory
      effects of the hydrolyzed degree of PVAs on the precipitation of a drug, and
      demonstrating the intermolecular interaction between PVAs and a drug using NOESY
      in water.

PMID- 30110622
TI  - What's in a (Sub)strain?
AB  - C57BL/6J and C57BL/6N inbred mice are widely, and often interchangeably, used for
      stem cell research; yet, these substrains harbor discrete genetic differences
      that can cause phenotypic disparities. In this issue of Stem Cell Reports,
      Morales-Hernandez et al. identify one particular difference-disruption of
      Nicotinamide Nucleotide Transhydrogenase (Nnt)-that increases reactive oxygen
      exposure and impairs hematopoietic progenitor cell function in C57BL/6J, as
      compared to C57BL/6N, mice.

PMID- 30110623
TI  - Pluri-IQ: Quantification of Embryonic Stem Cell Pluripotency through an Image
      Based Analysis Software.

PMID- 30110624
TI  - Coding of Self and Other's Future Choices in Dorsal Premotor Cortex during Social
      Interaction.
AB  - Representing others' intentions is central to primate social life. We explored
      the role of dorsal premotor cortex (PMd) in discriminating between self and
      others' behavior while two male rhesus monkeys performed a non-match-to-goal task
      in a monkey-human paradigm. During each trial, two of four potential targets were
      randomly presented on the right and left parts of a screen, and the monkey or the
      human was required to choose the one that did not match the previously chosen
      target. Each agent had to monitor the other's action in order to select the
      correct target in that agent's own turn. We report neurons that selectively
      encoded the future choice of the monkey, the human agent, or both. Our findings
      suggest that PMd activity shows a high degree of self-other differentiation
      during face-to-face interactions, leading to an independent representation of
      what others will do instead of entailing self-centered mental rehearsal or mirror
      like activities.

PMID- 30110625
TI  - Three Distinct Sets of Connector Hubs Integrate Human Brain Function.
AB  - Control over behavior is enabled by the brain's control networks, which interact
      with lower-level sensory motor and default networks to regulate their functions.
      Such interactions are facilitated by specialized "connector hub" regions that
      interconnect discrete networks. Previous work has treated hubs as a single
      category of brain regions, although their unitary nature is dubious when examined
      in individual brains. Here we investigated the nature of hubs by using fMRI to
      characterize individual-specific hub regions in two independent datasets. We
      identified three separable sets of connector hubs that integrate information
      between specific brain networks. These three hub categories occupy different
      positions within the brain's network structure; they affect networks differently
      when artificially lesioned, and they are differentially engaged during cognitive
      and motor task performance. This work suggests a model of brain organization in
      which different connector hubs integrate control functions and enable top-down
      control of separate processing streams.

PMID- 30110626
TI  - Changes in Glutathione Redox Potential Are Linked to Abeta42-Induced
      Neurotoxicity.
AB  - Glutathione is the major low-molecular weight thiol of eukaryotic cells. It is
      central to one of the two major NADPH-dependent reducing systems and is likely to
      play a role in combating oxidative stress, a process suggested to play a key role
      in Alzheimer's disease (AD). However, the nature and relevance of redox changes
      in the onset and progression of AD are still uncertain. Here, we combine
      genetically encoded redox sensors with our Drosophila models of amyloid-beta
      (Abeta) aggregation. We find that changes in glutathione redox potential (EGSH)
      closely correlate with disease onset and progression. We observe this redox
      imbalance specifically in neurons, but not in glia cells. EGSH changes and
      Abeta42 deposition are also accompanied by increased JNK stress signaling.
      Furthermore, pharmacologic and genetic manipulation of glutathione synthesis
      modulates Abeta42-mediated neurotoxicity, suggesting a causal relationship
      between disturbed glutathione redox homeostasis and early AD pathology.

PMID- 30110627
TI  - Attenuated Codon Optimality Contributes to Neural-Specific mRNA Decay in
      Drosophila.
AB  - Tissue-specific mRNA stability is important for cell fate and physiology, but the
      mechanisms involved are not fully understood. We found that zygotic mRNA
      stability in Drosophila correlates with codon content: optimal codons are
      enriched in stable transcripts associated with metabolic functions like
      translation, while non-optimal codons are enriched in unstable transcripts,
      including those associated with neural development. Bioinformatic analyses and
      reporter assays revealed that similar codons stabilize or destabilize mRNAs in
      the nervous system and other tissues, but the link between codon content and
      stability is attenuated in the nervous system. We confirmed that optimal codons
      are decoded by abundant tRNAs while non-optimal codons are decoded by less
      abundant tRNAs in embryos and in the nervous system. We conclude that codon
      optimality is a general determinant of zygotic mRNA stability, and attenuation of
      codon optimality allows trans-acting factors to exert greater influence over mRNA
      decay in the nervous system.

PMID- 30110628
TI  - Stress-Induced Low Complexity RNA Activates Physiological Amyloidogenesis.
AB  - Amyloid bodies (A-bodies) are inducible membrane-less nuclear compartments
      composed of heterogeneous proteins that adopt an amyloid-like state. A-bodies are
      seeded by noncoding RNA derived from stimuli-specific loci of the rDNA intergenic
      spacer (rIGSRNA). This raises the question of how rIGSRNA recruits a large
      population of diverse proteins to confer A-body identity. Here, we show that long
      low-complexity dinucleotide repeats operate as the architectural determinants of
      rIGSRNA. On stimulus, clusters of rIGSRNA with simple cytosine/uracil (CU) or
      adenosine/guanine (AG) repeats spanning hundreds of nucleotides accumulate in the
      nucleolar area. The low-complexity sequences facilitate charge-based interactions
      with short cationic peptides to produce multiple nucleolar liquid-like foci.
      Local concentration of proteins with fibrillation propensity in these nucleolar
      foci induces the formation of an amyloidogenic liquid phase that seeds A-bodies.
      These results demonstrate the physiological importance of low-complexity RNA and
      repetitive regions of the genome often dismissed as "junk" DNA.

PMID- 30110629
TI  - Enhancer Activity Requires CBP/P300 Bromodomain-Dependent Histone H3K27
      Acetylation.
AB  - Acetylation of histone H3 at lysine 27 is a well-defined marker of enhancer
      activity. However, the functional impact of this modification at enhancers is
      poorly understood. Here, we use a chemical genetics approach to acutely block the
      function of the cAMP response element binding protein (CREB) binding protein
      (CBP)/P300 bromodomain in models of hematological malignancies and describe a
      consequent loss of H3K27Ac specifically from enhancers, despite the continued
      presence of CBP/P300 at chromatin. Using this approach to dissect the role of
      H3K27Ac at enhancers, we identify a critical role for this modification in the
      production of enhancer RNAs and transcription of enhancer-regulated gene
      networks.

PMID- 30110630
TI  - Adaptive Evolution of MERS-CoV to Species Variation in DPP4.
AB  - Middle East Respiratory Syndrome Coronavirus (MERS-CoV) likely originated in bats
      and passed to humans through dromedary camels; however, the genetic mechanisms
      underlying cross-species adaptation remain poorly understood. Variation in the
      host receptor, dipeptidyl peptidase 4 (DPP4), can block the interaction with the
      MERS-CoV spike protein and form a species barrier to infection. To better
      understand the species adaptability of MERS-CoV, we identified a suboptimal
      species-derived variant of DPP4 to study viral adaption. Passaging virus on cells
      expressing this DPP4 variant led to accumulation of mutations in the viral spike
      which increased replication. Parallel passages revealed distinct paths of viral
      adaptation to the same DPP4 variant. Structural analysis and functional assays
      showed that these mutations enhanced viral entry with suboptimal DPP4 by altering
      the surface charge of spike. These findings demonstrate that MERS-CoV spike can
      utilize multiple paths to rapidly adapt to novel species variation in DPP4.

PMID- 30110632
TI  - RUNX Poly(ADP-Ribosyl)ation and BLM Interaction Facilitate the Fanconi Anemia
      Pathway of DNA Repair.
AB  - The Fanconi anemia (FA) pathway is a pivotal genome maintenance network that
      orchestrates the repair of DNA interstrand crosslinks (ICLs). The tumor
      suppressors RUNX1 and RUNX3 were shown to regulate the FA pathway independent of
      their canonical transcription activities, by controlling the DNA damage-dependent
      chromatin association of FANCD2. Here, in further biochemical characterization,
      we demonstrate that RUNX3 is modified by PARP-dependent poly(ADP-ribosyl)ation
      (PARylation), which in turn allows RUNX binding to DNA repair structures lacking
      transcription-related RUNX consensus motifs. SILAC-based mass spectrometric
      analysis revealed significant association of RUNX3 with core DNA repair
      complexes, including PARP1, even in unstressed cells. After DNA damage, the
      increased interaction between RUNX3 and BLM facilitates efficient FANCD2
      chromatin localization. RUNX-Walker motif mutations from breast cancers are
      impaired for DNA damage-inducible PARylation, unveiling a potential mechanism for
      FA pathway inactivation in cancers. Our results reinforce the emerging paradigm
      that RUNX proteins are tumor suppressors with genome gatekeeper function.

PMID- 30110633
TI  - Resolving ESCRT-III Spirals at the Intercellular Bridge of Dividing Cells Using
      3D STORM.
AB  - The ESCRT machinery mediates membrane fission in a variety of processes in cells.
      According to current models, ESCRT-III proteins drive membrane fission by
      assembling into helical filaments on membranes. Here, we used 3D STORM imaging of
      endogenous ESCRT-III component IST1 to reveal the evolution of the structural
      organization of ESCRT-III in mammalian cytokinetic abscission. Using this
      approach, ESCRT-III ring and spiral assemblies were resolved and characterized at
      different stages of abscission. Visualization of IST1 structures in cells lacking
      the microtubule-severing enzyme spastin and in cells depleted of specific ESCRT
      III components or the ATPase VPS4 demonstrated the contribution of these
      components to the organization and function of ESCRTs in cells. This work
      provides direct evidence that ESCRT-III proteins form helical filaments to
      mediate their function in cells and raises new mechanistic scenarios for ESCRT
      driven cytokinetic abscission.

PMID- 30110631
TI  - Von Hippel-Lindau Protein Is Required for Optimal Alveolar Macrophage Terminal
      Differentiation, Self-Renewal, and Function.
AB  - The rapid transit from hypoxia to normoxia in the lung that follows the first
      breath in newborn mice coincides with alveolar macrophage (AM) differentiation.
      However, whether sensing of oxygen affects AM maturation and function has not
      been previously explored. We have generated mice whose AMs show a deficient
      ability to sense oxygen after birth by deleting Vhl, a negative regulator of HIF
      transcription factors, in the CD11c compartment (CD11cDeltaVhl mice). VHL
      deficient AMs show an immature-like phenotype and an impaired self-renewal
      capacity in vivo that persists upon culture ex vivo. VHL-deficient phenotype is
      intrinsic in AMs derived from monocyte precursors in mixed bone marrow chimeras.
      Moreover, unlike control Vhlfl/fl, AMs from CD11cDeltaVhl mice do not reverse
      pulmonary alveolar proteinosis when transplanted into Csf2rb-/- mice,
      demonstrating that VHL contributes to AM-mediated surfactant clearance. Thus, our
      results suggest that optimal AM terminal differentiation, self-renewal, and
      homeostatic function requires their intact oxygen-sensing capacity.

PMID- 30110634
TI  - A Zombie LIF Gene in Elephants Is Upregulated by TP53 to Induce Apoptosis in
      Response to DNA Damage.
AB  - Large-bodied organisms have more cells that can potentially turn cancerous than
      small-bodied organisms, imposing an increased risk of developing cancer. This
      expectation predicts a positive correlation between body size and cancer risk;
      however, there is no correlation between body size and cancer risk across species
      ("Peto's paradox"). Here, we show that elephants and their extinct relatives
      (proboscideans) may have resolved Peto's paradox in part through
      refunctionalizing a leukemia inhibitory factor pseudogene (LIF6) with pro
      apoptotic functions. LIF6 is transcriptionally upregulated by TP53 in response to
      DNA damage and translocates to the mitochondria where it induces apoptosis.
      Phylogenetic analyses of living and extinct proboscidean LIF6 genes indicates
      that its TP53 response element evolved coincident with the evolution of large
      body sizes in the proboscidean stem lineage. These results suggest that
      refunctionalizing of a pro-apoptotic LIF pseudogene may have been permissive
      (although not sufficient) for the evolution of large body sizes in proboscideans.

PMID- 30110635
TI  - Clonal Expansion and Diversification of Cancer-Associated Mutations in
      Endometriosis and Normal Endometrium.
AB  - Endometriosis is characterized by ectopic endometrial-like epithelium and stroma,
      of which molecular characteristics remain to be fully elucidated. We sequenced
      107 ovarian endometriotic and 82 normal uterine endometrial epithelium samples
      isolated by laser microdissection. In both endometriotic and normal epithelium
      samples, numerous somatic mutations were identified within genes frequently
      mutated in endometriosis-associated ovarian cancers. KRAS is frequently mutated
      in endometriotic epithelium, with a higher mutant allele frequency (MAF)
      accompanied by arm-level allelic imbalances. Analyses of MAF, combined with
      multiregional sequencing, illuminated spatiotemporal evolution of the
      endometriosis and uterine endometrium genomes. We sequenced 109 single
      endometrial glands and found that each gland carried distinct cancer-associated
      mutations, demonstrating the heterogeneity of the genomic architecture of
      endometrial epithelium. Remarkable increases in MAF of mutations in cancer
      associated genes in endometriotic epithelium suggest retrograde flow of
      endometrial cells already harboring cancer-associated mutations, with selective
      advantages at ectopic sites, leading to the development of endometriosis.

PMID- 30110636
TI  - Blocking the FSTL1-DIP2A Axis Improves Anti-tumor Immunity.
AB  - Immune dysfunction is a strong factor in the resistance of cancer to treatment.
      Blocking immune checkpoint pathways is a promising approach to improve anti-tumor
      immunity, but the clinical efficacies are still limited. We previously identified
      follistatin-like 1 (FSTL1) as a determinant of immune dysfunction mediated by
      mesenchymal stromal/stem cells (MSCs) and immunoregulatory cells. Here, we
      demonstrate that blocking FSTL1 but not immune checkpoint pathways significantly
      suppresses cancer progression and metastasis in several mouse tumor models with
      increased MSCs. Expression of DIP2A (the receptor of FSTL1) in tumor cells is
      critical for FSTL1-induced immunoresistance. FSTL1/DIP2A co-positivity in tumor
      tissues correlates with poor prognosis in NSCLC patients. Thus, breaking the
      FSTL1-DIP2A axis may be a useful strategy for successfully inducing anti-tumor
      immunity.

PMID- 30110637
TI  - Antibody-Dependent Enhancement of Ebola Virus Infection by Human Antibodies
      Isolated from Survivors.
AB  - Some monoclonal antibodies (mAbs) recovered from survivors of filovirus
      infections can protect against infection. It is currently unknown whether natural
      infection also induces some antibodies with the capacity for antibody-dependent
      enhancement (ADE). A panel of mAbs obtained from human survivors of filovirus
      infection caused by Ebola, Bundibugyo, or Marburg viruses was evaluated for their
      ability to facilitate ADE. ADE was observed readily with all mAbs examined at sub
      neutralizing concentrations, and this effect was not restricted to mAbs with a
      particular epitope specificity, neutralizing capacity, or subclass. Blocking of
      specific Fcgamma receptors reduced but did not abolish ADE that was associated
      with high-affinity binding antibodies, suggesting that lower-affinity
      interactions still cause ADE. Mutations of Fc fragments of an mAb that altered
      its interaction with Fc receptors rendered the antibody partially protective in
      vivo at a low dose, suggesting that ADE counteracts antibody-mediated protection
      and facilitates dissemination of filovirus infections.

PMID- 30110639
TI  - Lnk/Sh2b3 Regulates Adipose Inflammation and Glucose Tolerance through Group 1
      ILCs.
AB  - Lnk/Sh2b3 is an adaptor protein that negatively regulates cytokine signaling in
      lymphohematopoiesis. A missense variant within the LNK/SH2B3 gene has been
      reported to be a risk variant for several autoimmune diseases, including
      diabetes. We found that glucose tolerance and insulin responses were impaired in
      Lnk-/- mice. Moreover, immune cells such as group 1 innate lymphoid cells (G1
      ILCs), CD8+ T cells, and M1 macrophages accumulated in adipose tissue. When Lnk-/
      mice were crossed with Il15-/- mice or depleted of G1-ILCs but not CD8+ T cells,
      glucose intolerance and adipose inflammation were ameliorated. Lnk-/- G1-ILCs
      showed activated phenotypes as well as enhanced reactivity for IL-15, and
      administration of a JAK inhibitor improved glucose tolerance. Accordingly, a high
      fat diet greatly worsened glucose intolerance in Lnk-/- mice. Thus, Lnk/Sh2b3
      controls homeostasis in adipose tissue and reduces the risk of onset of diabetes
      by regulating the expansion and activation of IL-15-dependent adipose G1-ILCs.

PMID- 30110638
TI  - Antibody Repertoires to the Same Ebola Vaccine Antigen Are Differentially
      Affected by Vaccine Vectors.
AB  - Comparative immune response profiling is important for selecting next-generation
      vaccines. We comprehensively evaluated the antibody responses from a panel of
      nine respiratory vaccines against Ebola virus (EBOV) derived from human and avian
      paramyxoviruses expressing EBOV glycoprotein (GP). Most vaccines were protective
      in guinea pigs but yielded antibody repertoires that differed in proportion
      targeting key antigenic regions, avidity, neutralizing antibody specificities,
      and linear epitope preferences. Competition studies with monoclonal antibodies
      from human survivors revealed that some epitopes in GP targeted for
      neutralization were vector dependent, while EBOV-neutralizing titers correlated
      with the response magnitude toward the receptor-binding domain and GP1/GP2
      interface epitopes. While an immunogen determines the breadth of antibody
      response, distinct vaccine vectors can induce qualitatively different responses,
      affecting protective efficacy. These data suggest that immune correlates of
      vaccine protection cannot be generalized for all vaccines against the same
      pathogen, even if they use the exact same immunogen.

PMID- 30110640
TI  - Orthogonal Dietary Niche Enables Reversible Engraftment of a Gut Bacterial
      Commensal.
AB  - Interest in manipulating the gut microbiota to treat disease has led to a need
      for understanding how organisms can establish themselves when introduced into a
      host with an intact microbial community. Here, we employ the concept of
      orthogonal niche engineering: a resource typically absent from the diet, seaweed,
      creates a customized niche for an introduced organism. In the short term, co
      introduction of this resource at 1% in the diet along with an organism with
      exclusive access to this resource, Bacteroides plebeius DSM 17135, enables it to
      colonize at a median abundance of 1% and frequently up to 10 or more percent,
      both on pulsed and constant seaweed diets. In a two-month follow-up after the
      initial treatment period, B. plebeius stops responding to seaweed in mice
      initially on the constant seaweed diet, suggesting treatment regime will affect
      controllability. These results offer potential for diet-based intervention to
      introduce and control target organisms.

PMID- 30110643
TI  - The C. elegans BRCA2-ALP/Enigma Complex Regulates Axon Regeneration via a Rho
      GTPase-ROCK-MLC Phosphorylation Pathway.
AB  - The ability of specific neurons to regenerate their axons after injury is
      governed by cell-intrinsic regeneration pathways. However, the mechanisms
      regulating axon regeneration are not well understood. Here, we identify the brc-2
      gene encoding a homolog of the mammalian BRCA2 tumor suppressor as a regulator of
      axon regeneration in Caenorhabditis elegans motor neurons. We show that the RHO
      1/Rho GTPase-LET-502/ROCK (Rho-associated coiled-coil kinase)-regulatory non
      muscle myosin light-chain (MLC-4/MLC) phosphorylation signaling pathway regulates
      axon regeneration. BRC-2 functions between RHO-1 and LET-502, suggesting that BRC
      2 is required for the activation of LET-502 by RHO-1-GTP. We also find that one
      component that interacts with BRC-2, the ALP (alpha-actinin-associated LIM
      protein)/Enigma protein ALP-1, is required for regeneration and acts between LET
      502 and MLC-4 phosphorylation. Furthermore, we demonstrate that ALP-1 associates
      with LET-502 and MLC-4. Thus, ALP-1 serves as a platform to activate MLC-4
      phosphorylation mediated by the RHO-1-LET-502 signaling pathway.

PMID- 30110641
TI  - Maf1 and Repression of RNA Polymerase III-Mediated Transcription Drive Adipocyte
      Differentiation.
AB  - RNA polymerase (pol) III transcribes a variety of small untranslated RNAs
      involved in transcription, RNA processing, and translation. RNA pol III and its
      components are altered in various human developmental disorders, yet their roles
      in cell fate determination and development are poorly understood. Here we
      demonstrate that Maf1, a transcriptional repressor, promotes induction of mouse
      embryonic stem cells (mESCs) into mesoderm. Reduced Maf1 expression in mESCs and
      preadipocytes impairs adipogenesis, while ectopic Maf1 expression in Maf1
      deficient cells enhances differentiation. RNA pol III repression by chemical
      inhibition or knockdown of Brf1 promotes adipogenesis. Altered RNA pol III
      dependent transcription produces select changes in mRNAs with a significant
      enrichment of adipogenic gene signatures. Furthermore, RNA pol III-mediated
      transcription positively regulates long non-coding RNA H19 and Wnt6 expression,
      established adipogenesis inhibitors. Together, these studies reveal an important
      and unexpected function for RNA pol III-mediated transcription and Maf1 in
      mesoderm induction and adipocyte differentiation.

PMID- 30110644
TI  - Identification, Biosynthesis, and Decapping of NAD-Capped RNAs in B. subtilis.
AB  - The ubiquitous coenzyme nicotinamide adenine dinucleotide (NAD) decorates various
      RNAs in different organisms. In the proteobacterium Escherichia coli, the NAD-cap
      confers stability against RNA degradation. To date, NAD-RNAs have not been
      identified in any other bacterial microorganism. Here, we report the
      identification of NAD-RNA in the firmicute Bacillus subtilis. In the late
      exponential growth phase, predominantly mRNAs are NAD modified. NAD is
      incorporated de novo into RNA by the cellular RNA polymerase using non-canonical
      transcription initiation. The incorporation efficiency depends on the -1 position
      of the promoter but is independent of sigma factors or mutations in the
      rifampicin binding pocket. RNA pyrophosphohydrolase BsRppH is found to decap NAD
      RNA. In vitro, the decapping activity is facilitated by manganese ions and single
      stranded RNA 5' ends. Depletion of BsRppH influences the gene expression of ~13%
      of transcripts in B. subtilis. The NAD-cap stabilizes RNA against 5'-to-3'
      exonucleolytic decay by RNase J1.

PMID- 30110642
TI  - Neuronal-Specific TUBB3 Is Not Required for Normal Neuronal Function but Is
      Essential for Timely Axon Regeneration.
AB  - We generated a knockout mouse for the neuronal-specific beta-tubulin isoform
      Tubb3 to investigate its role in nervous system formation and maintenance. Tubb3
      /- mice have no detectable neurobehavioral or neuropathological deficits, and
      upregulation of mRNA and protein of the remaining beta-tubulin isotypes results
      in equivalent total beta-tubulin levels in Tubb3-/- and wild-type mice. Despite
      similar levels of total beta-tubulin, adult dorsal root ganglia lacking TUBB3
      have decreased growth cone microtubule dynamics and a decreased neurite outgrowth
      rate of 22% in vitro and in vivo. The effect of the 22% slower growth rate is
      exacerbated for sensory recovery, where fibers must reinnervate the full volume
      of the skin to recover touch function. Overall, these data reveal that, while
      TUBB3 is not required for formation of the nervous system, it has a specific role
      in the rate of peripheral axon regeneration that cannot be replaced by other beta
      tubulins.

PMID- 30110646
TI  - Proteomic Characterization of the Heart and Skeletal Muscle Reveals Widespread
      Arginine ADP-Ribosylation by the ARTC1 Ectoenzyme.
AB  - The clostridium-like ecto-ADP-ribosyltransferase ARTC1 is expressed in a highly
      restricted manner in skeletal muscle and heart tissue. Although ARTC1 is well
      studied, the identification of ARTC1 targets in vivo and subsequent
      characterization of ARTC1-regulated cellular processes on the proteome level have
      been challenging and only a few ARTC1-ADP-ribosylated targets are known. Applying
      our recently developed mass spectrometry-based workflow to C2C12 myotubes and to
      skeletal muscle and heart tissues from wild-type mice, we identify hundreds of
      ARTC1-ADP-ribosylated proteins whose modifications are absent in the ADP
      ribosylome of ARTC1-deficient mice. These proteins are ADP-ribosylated on
      arginine residues and mainly located on the cell surface or in the extracellular
      space. They are associated with signal transduction, transmembrane transport, and
      muscle function. Validation of hemopexin (HPX) as a ARTC1-target protein
      confirmed the functional importance of ARTC1-mediated extracellular arginine ADP
      ribosylation at the systems level.

PMID- 30110647
TI  - Differential HDAC6 Activity Modulates Ciliogenesis and Subsequent Mechanosensing
      of Endothelial Cells Derived from Pluripotent Stem Cells.

PMID- 30110645
TI  - Large-Scale Human Dendritic Cell Differentiation Revealing Notch-Dependent
      Lineage Bifurcation and Heterogeneity.
AB  - The ability to generate large numbers of distinct types of human dendritic cells
      (DCs) in vitro is critical for accelerating our understanding of DC biology and
      harnessing them clinically. We developed a DC differentiation method from human
      CD34+ precursors leading to high yields of plasmacytoid DCs (pDCs) and both types
      of conventional DCs (cDC1s and cDC2s). The identity of the cells generated in
      vitro and their strong homology to their blood counterparts were demonstrated by
      phenotypic, functional, and single-cell RNA-sequencing analyses. This culture
      system revealed a critical role of Notch signaling and GM-CSF for promoting cDC1
      generation. Moreover, we discovered a pre-terminal differentiation state for each
      DC type, characterized by high expression of cell-cycle genes and lack of XCR1 in
      the case of cDC1. Our culture system will greatly facilitate the simultaneous and
      comprehensive study of primary, otherwise rare human DC types, including their
      mutual interactions.

PMID- 30110649
TI  - Maternal dairy fat diet does not influence neurotrophin levels and cognitive
      performance in the rat offspring at adult age.
AB  - Cognitive development may be influenced by maternal nutrition especially fats.
      Indian population is vegetarian and main source of fat is dairy. This study
      investigates the effect of dairy fat consumption during pregnancy in an animal
      model on fatty acids, brain neurotrophins (brain derived neurotrophic factor:
      BDNF; and nerve growth factor: NGF) and cognitive performance in adult offspring.
      Pregnant Wistar rats were assigned to control (Control C) and four treatment
      groups: High fat diet (HFD); High fat diet supplemented with omega-3 fatty acids
      (HFDO); High fat diet deficient in vitamin B12 (HFBD); High fat deficient in
      vitamin B12 supplemented with omega-3 fatty acids (HFBDO). Half the dams were
      dissected on d20 of gestation, and the brains of their pups were collected. The
      remaining dams delivered on d22 of gestation and were assigned to a control diet.
      The cognitive performance of these adult offspring was assessed at 6 mo of age.
      Brain fatty acids were comparable to control in the pups at birth and offspring
      at 6 mo of age. The protein levels of BDNF in the pup brain at birth were lower
      in both the HFD (p < 0.01) and HFBD (p < 0.05) groups as compared to control. The
      mRNA levels of TrK B were lower (p < 0.05) in the pup brain at birth in the HFD
      as compared to control group. In the offspring at 6 mo of age the protein levels
      of BDNF and NGF in all the treatment groups were similar to that of control.
      However, the mRNA levels of only BDNF (p < 0.01 for both) were higher in the HFBD
      group as compared to both control and HFD groups. The cognitive performance of
      the adult offspring from various dietary groups was similar to control. In
      conclusion, consumption of a maternal high dairy fat diet although lowered the
      levels of brain BDNF in the pup at birth it does not affect the cognitive health
      of the adult offspring.

PMID- 30110648
TI  - Identification and expression profiling of all Hsp family member genes under
      salinity stress in different poplar clones.
AB  - Heat shock proteins (Hsps) play a key role for regulation of the changes during
      different stress conditions including salinity, drought, heavy metal and extreme
      temperature. Molecular based studies on the response mechanisms of forest trees
      to abiotic stresses started in 2006 when Populus trichocarpa genome sequence was
      completed as a model tree species. In recent years, bioinformatic analyzes have
      been carried out to determine functional gene regions of tree species. In this
      study, sHsp, Hsp40, Hsp60, Hsp90 and Hsp100 gene family members were identified
      in poplar genome. Some bioinformatics analyses were conducted, such as:
      identification of DNA/protein sequences, chromosomal localization, gene
      structure, calculation of genomic duplications, determination of phylogenetic
      groups, examination of protected motif regions, identification of gene ontology
      categories, modeling of protein 3D structure, determination of miRNA targeting
      genes, examination of sHsp, Hsp40, Hsp60, Hsp90 and Hsp100 gene family members in
      transcriptome data during salinity stress. As a result of bioinformatic analyzes
      made on P. trichocarpa genome; 60, 145, 49, 34, 12 and 90 genes belonging to
      members of sHsp, Hsp40, Hsp60, Hsp70, Hsp90 and Hsp100 protein families were
      firstly defined within the scope of this study. A total of 390 genes belonging to
      all Hsps gene families were characterized using different bioinformatics tools.
      In addition, salinity stress was applied to Populus tremula L. (Samsun) naturally
      grown in Turkey, Hybrid poplar species I-214 (Populus euramericana Dode. Guinier)
      and Black Poplar species (Populus nigra L.), Geyve and N.03.368.A clones. The
      expression levels of the selected Hsps genes were determined by the qRT-PCR
      method. After salt stress application in various poplar clones, expression levels
      of genes including PtsHsp-11, PtsHsp-21, PtsHsp-36, PtHsp40-113, PtHsp40-117,
      PtHsp60-31, PtHsp60-33, PtHsp60-38, PtHsp60-49, PtHsp70-09, PtHsp70-12, 33,
      PtHsp90-09, PtHsp90-12, PtHsp100-21, and PtHsp100-75 were increased. The role of
      the Hsps genes during salt stress has been revealed. Together with detailed
      bioinformatics analyses, gene expression analysis greatly contributes to
      understand functions of these gene family members. This research serves as a
      blueprint for future studies and offers a significant clue for the further study
      of the functions of this important gene family. Moreover, determined genes in
      this study can also be used for cloning studies in agricultural practices.

PMID- 30110650
TI  - Regional volumetric abnormalities in pediatric autism revealed by structural
      magnetic resonance imaging.
AB  - Autism is a group of complex neurodevelopmental disorders characterized by
      impaired social interaction, restricted and repetitive behavior. We performed a
      large-scale retrospective analysis of 1,996 structural magnetic resonance imaging
      (MRI) examinations of the brain from 1,769 autistic and neurologically typically
      developing patients (aged 0-32 years), and extracted regional volumetric
      measurements distributed across 463 brain regions of each patient. The youngest
      autistic patients (<2.5 years) were diagnosed after imaging and identified
      retrospectively. Our study demonstrates corpus callosum volumetric abnormalities
      among autistic patients that are associated with brain overgrowth in early
      childhood (0-5 years old), followed by a shift towards known decreased volumes in
      later ages. Results confirm known increases in ventricular volumes among autistic
      populations and extends those findings to increased volumes of the choroid
      plexus. Our study also demonstrates distributed volumetric abnormalities among
      autistic patients that affect a variety of key regional white and grey matter
      areas of the brain potentially associated with known symptoms of autism.

PMID- 30110651
TI  - AMP-activated protein kinase sparks the fire of cardioprotection against
      myocardial ischemia and cardiac ageing.
AB  - AMP-activated protein kinase (AMPK) is a pivotal regulator of some endogenous
      defensive molecules in various pathological processes, particularly myocardial
      ischemia (MI), a high risk of myocardial infarction. Thereby it is of great
      significance to explore the inherent mechanism between AMPK and myocardial
      infarction. In this review, we first introduce the structure and role of AMPK in
      the heart. Next, we introduce the mechanisms of AMPK in the heart; followed by
      the energy regulation of AMPK in MI. Lastly, the attention will be expanded to
      some potential directions and further perspectives. The information compiled here
      will be helpful for further research and drug design in the future before AMPK
      might be considered as a therapeutic target of MI.

PMID- 30110652
TI  - 15-Lipoxygenase-2/15(S)-hydroxyeicosatetraenoic acid regulates cell proliferation
      and metastasis via the STAT3 pathway in lung adenocarcinoma.
AB  - 15-Lipoxygenase-2 (15-LOX-2) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)
      have been considered as latent mediators of diverse biological processes
      including cancer. However, their functions in lung adenocarcinoma (LAC) are
      unclear. In this study, we aimed to determine whether 15-LOX-2/15(S)-HETE is
      involved in the proliferation and migration of A549 cells and to identify the
      signaling pathways that participate in this process. We used immunohistochemistry
      to identify the expression levels of 15-LOX-2 in lung cancer tissue samples. The
      effects of 15(S)-HETE on the proliferation and migration of A549 cells under
      hypoxic conditions were assessed by cell viability assays, immunofluorescence,
      western blotting, scratch wound assays and transwell assays. We found that the
      expression of 15-LOX-2 was significantly up-regulated in LAC tissue samples
      compared with adjacent normal tissue samples. The content of 15(S)-HETE in A549
      cells was increased under hypoxic conditions. Moreover, 15(S)-HETE could
      stimulate the expression of PCNA, cyclin A and cyclin D. In addition, siRNA of 15
      LOX-2 inhibited the proliferation and migration of A549 cells in vitro. Our data
      also provide novel evidence demonstrating that the STAT3 pathway participates in
      the 15(S)-HETE-induced proliferation and migration of A549 cells. This study may
      provide a greater understanding of LAC metastasis and shed new light on the
      mechanisms by which the 15(S)-HETE/STAT3 pathway is related to this disease.

PMID- 30110653
TI  - On the systematics of some marine haploporids (Trematoda) with the description of
      a new species of Megasolena Linton, 1910.
AB  - Megasolena mikra sp. nov. is described from the queen angelfish, Holacanthus
      ciliaris (Linnaeus), off Florida, USA. The new species can be differentiated from
      all other species of Megasolena Linton, 1910 except Megasolena littoralis Munoz,
      George-Nascimento, and Bray, 2017 in possessing testes that are smaller in
      diameter than the ovary. The new species can be differentiated from M. littoralis
      in lacking tegumental spines and possessing oral sucker papillae. Molecular data
      are provided for two species each of Cadenatella Dollfus, 1946, Hapladena Linton,
      1910, and Megasolena Linton, 1910. Bayesian inference analysis of concatenated
      internal transcribed spacer region-2 (ITS2) and partial 28S rDNA sequences of 50
      haploporoids revealed 1) a monophyletic Atractotrematidae Yamaguti, 1939 sister
      to the rest of the haploporoids tested; 2) a paraphyletic Megasoleninae Manter,
      1935 - if Hapladena is included; and 3) a monophyletic Cadenatellinae Gibson and
      Bray, 1982 sister to the 'mugilid' haploporids. The 'mugilid' haploporids formed
      a monophyletic clade consisting of the subfamilies Chalcinotrematinae Overstreet
      and Curran, 2005, Forticulcitinae Blasco-Costa, Balbuena, Kostadinova, and Olson,
      2009, Haploporinae Nicoll, 1914, and Waretrematinae Srivastava, 1937. Based on
      our analysis we restrict the Megasoleninae to include Megasolena, Vitellibaculum
      Montgomery, 1957, and Metamegasolena Yamaguti, 1970, all of which have species
      with two testes. To accommodate the former megasolenine taxa with a single
      testis, we erect the Hapladeninae subf. nov. for species in Hapladena and
      tentatively, Myodera Montgomery, 1957. Our results further support that
      haploporoids had a common marine ancestor with two testes, and that members of
      the Haploporoidea Nicoll, 1914 underwent diversification following a shift from a
      primarily marine life history with eupercarian hosts to a more euryhaline one
      with diadromous hosts (namely mullet).

PMID- 30110654
TI  - Seroprevalence of Cryptosporidium parvum and Neospora caninum in cattle in the
      southern Kyushu region of Japan.
AB  - Cryptosporidium parvum and Neospora caninum are common parasites in domesticated
      cattle worldwide, including in Japan. We carried out a serological survey to
      detect C. parvum and N. caninum infection among cattle in the southern Kyushu
      region of Japan-including the small islands-by indirect enzyme-linked
      immunosorbent assay based on recombinant antigens. We found that total
      seropositivity in 570 Japanese black cattle was 96.3% for C. parvum and 18.4% for
      N. caninum. Although seroprevalence was correlated with cattle age, differences
      in the seroprevalence of C. parvum among age groups were not statistically
      significant. On the other hand, N. caninum seroprevalence increased with age,
      suggesting horizontal transmission through ingestion of food or water
      contaminated with oocysts. These findings underscore the importance of monitoring
      C. parvum and N. caninum in cattle and implementing measures to prevent the
      spread of infection to other livestock and to humans.

PMID- 30110655
TI  - Enhanced transgene expression using cis-acting elements combined with the EF1
      promoter in a mammalian expression system.
AB  - Transgene expression in eukaryotic cells suffers from epigenetic effects that
      result in low or unstable transgene expression and high clonal variability. The
      use of epigenetic regulators is a promising approach to alleviating such unwanted
      effects. we investigated the effect of the strong human EF1-alpha promoter
      combined with six cis-acting elements on transgene expression in transfected
      Chinese hamster ovary (CHO) cells. The six elements included the human
      cytomegalovirus immediate early core promoter element (hCPE), three synthetic
      enhancer element (SEE1, SEE2, Syn1), human cytomegalovirus immediate early
      enhancer (hCMV-IEE), and a regulatory element isolated from CHO-K1 genomic DNA
      (C77). The respective vectors were transfected into CHO cells, and stably
      transfected cell pools were screened and analyzed for transgene expression. The
      results showed that SEE1 increased transient expression most strongly. However,
      hCPE enhanced eGFP transgene expression most significantly in stably transfected
      CHO cells, by about 2.45-fold. Erythropoietin expression analysis showed that
      hCPE induced the highest EPO productivity, followed by hCMV-IEE. We found that
      the enhancing effect of hCPE and hCMV-IEE was related with transgene copy number.
      In conclusion, we found that hCPE and hCMV-IEE cis-acting elements combine with
      EF1-alpha can increase recombinant protein expression in CHO cells.

PMID- 30110656
TI  - Molecular identification of Mesocestoides sp. metacestodes in a captive gold
      handed tamarin (Saguinus midas).
AB  - Mesocestoides spp. are tapeworms harbored in the intestine of many domestic and
      wild carnivores, birds of prey and, rarely, of humans. The life cycle is assumed
      to involve three hosts and the metacestode juvenile stage (tetrathyridium) may
      reproduce asexually, provoking severe systemic infections. In the present study,
      a case of a peritoneal infection by Mesocestoides sp. occurred in a captive gold
      handed tamarin (Saguinus midas) is described. Phylogenetic positions based on CO1
      and 12S loci were analysed to describe in details this unusual finding of
      Mesocestoides in a callitrichid monkey. The phylogenetic analyses has not clearly
      resolve relationships between the metacestode forms from the tamarin and any of
      the described Mesocestoides species available so far, including those described
      from non-human primates, thus supporting the hypothesis of a new taxon within the
      genus.

PMID- 30110657
TI  - The 3-D structure of VNG0258H/RosR - A haloarchaeal DNA-binding protein in its
      ionic shell.
AB  - Protein-DNA interactions are highly dependent on salt concentration. To gain
      insight into how such interactions are maintained in the highly saline cytoplasm
      of halophilic archaea, we determined the 3-D structure of VNG0258H/RosR, the
      first haloarchaeal DNA-binding protein from the extreme halophilic archaeon
      Halobactrium salinarum. It is a dimeric winged-helix-turn-helix (wHTH) protein
      with unique features due to adaptation to the halophilic environment. As ions are
      major players in DNA binding processes, particularly in halophilic environments,
      we investigated the solution structure of the ionic envelope and located anions
      in the first shell around the protein in the crystal using anomalous scattering.
      Anions that were found to be tightly bound to residues in the positively charged
      DNA-binding site would probably be released upon DNA binding and will thus make
      significant contribution to the driving force of the binding process.
      Unexpectedly, ions were also found in a buried internal cavity connected to the
      external medium by a tunnel. Our structure lays a solid groundwork for future
      structural, computational and biochemical studies on complexes of the protein
      with cognate DNA sequences, with implications to protein-DNA interactions in
      hyper-saline environments.

PMID- 30110658
TI  - Role of adipokinetic hormone during starvation in Drosophila.
AB  - The role of adipokinetic hormone (Drome-AKH) in maintaining the levels of basic
      nutrients, under starvation conditions, was studied using Drosophila melanogaster
      mutants with AKH deficiency (Akh1) and AKH abundance (EE-Akh). Our results showed
      lipids as the main energy reserve in Drosophila, and their physiological level
      and metabolism were shown to be under the control of AKH. AKH abundance in the
      body resulted in lower levels of triacylglycerols and diacylglycerols than in the
      controls, probably due to a more intensive metabolism; interestingly, there was a
      disproportional representation of fatty acids in triacylglycerols and
      diacylglycerols in Drosophila. Lower level of glycogen and its partial control by
      AKH suggest its lesser role as the storage substance. However, maintenance of
      free carbohydrate level in Drosophila seemed to be critical; when glycogen stores
      are exhausted, carbohydrates are synthesized from other sources. Protein levels
      and their alterations, under starvation, did not seem controlled by AKH. AKH
      deficient flies were more resistant while AKH-abundant flies were more sensitive
      to starvation; females were found to be more resistant than males, regardless of
      the AKH level, probably due to higher body mass and higher amount of nutrients.
      However, in accordance with the level of all nutrients, that of AKH also
      gradually decreased with prolonged starvation.

PMID- 30110660
TI  - The auditory cortex network in the posterior superior temporal area.
AB  - OBJECTIVE: This study investigated the function and networks of the auditory
      cortices in the posterior lateral superior temporal area (PLST) using a
      combination of electrical cortical stimulation and diffusion tensor imaging
      (DTI). METHODS: Seven patients with intractable focal epilepsy in which the PLST
      auditory cortices were identified during the electrical cortical stimulation were
      enrolled in this study (left side: four patients, right side: three patients).
      Electrical stimulation at 50 Hz was applied to the chronically implanted subdural
      electrodes to identify the PLST auditory cortices. DTI was used to identify the
      subcortical fibers originating from the PLST auditory cortices found by
      electrical stimulation. RESULTS: Electrical stimulation of the right PLST
      auditory cortices induced hearing impairment in three patients and left side
      stimulation elicited hearing illusory sounds in four patients. DTI detected the
      middle longitudinal fasciculus (MLF) in all patients, the superior longitudinal
      fasciculus (SLF) in six patients and the inferior fronto-occipital fasciculus
      (IFOF) in three patients, originating from the PLST auditory cortices.
      CONCLUSION: This study suggests different functional roles between the right and
      left PLST auditory cortices, and the networks originating from these areas.
      SIGNIFICANCE: MLF, SLF and IFOF might be associated with the auditory processing.

PMID- 30110659
TI  - Molecular cloning and functional expression of the 5-HT7 receptor in Chinese
      mitten crab (Eriocheir sinensis).
AB  - Serotonin (5-HT) regulates numerous physiological functions and processes, such
      as light adaptation, food intake and ovarian maturation, and plays the role
      through 5-HT receptors. To our knowledge, this is the first study to isolate and
      characterize the serotonin receptor 7 (5-HT7 receptor) cDNA encoded in Eriocheir
      sinensis, an economically important aquaculture species in China, by performing
      rapid-amplification of cDNA ends. The full-length of 5-HT7 receptor gene cDNA is
      2328 bp and encodes a polypeptide with 590 amino acids that are highly homologous
      with other crustaceans 5-HT7 receptor genes. Analysis of the deduced amino acid
      sequence of the 5-HT7, including 7 transmembrane domains and some common features
      of G protein-coupled receptors (GPCRs), indicated that 5-HT7 receptor was a
      member of GPCRs family. A gene expression analysis of the 5-HT7 receptor by RT
      PCR revealed that the 5-HT7 receptor transcripts were widely distributed in
      various tissues, in which high expression levels were observed in the cranial
      ganglia, thoracic ganglia and intestines. Further study about the effects of
      photoperiods on the 5-HT7 expression in the tissues showed that a significantly
      increasing expression of the 5-HT7 receptor was observed in the thoracic ganglia
      induced by constant light. In addition, in the eyestalks, the expression levels
      of 5-HT7 mRNA in constant darkness and constant light were lower than control
      treatment. Then, the expression levels of the 5-HT7 receptor in three feeding
      statuses displayed that there were significantly increasing expressions in the
      hepatopancreas and intestines after feeding, compared with before feeding and
      during the feeding period. Finally, the 5-HT7 mRNA expression levels in stage III
      and stage IV were higher than the levels in stage I of ovarian development. Our
      experimental results showed that the 5-HT7 receptor structurally belongs to
      GPCRs, and the thoracic ganglia and eyestalks are the important tissues of the 5
      HT7 receptor for light adaptation. The 5-HT7 receptor may also be involved in the
      physiological regulation of the hepatopancreas and intestines after ingestion in
      E. sinensis. In addition, the 5-HT7 receptor is involved in the process of
      ovarian maturation. The study provided a foundation for further research of light
      adaptation, digestive functions and ovarian maturation of the 5-HT7 receptor in
      Decapoda.

PMID- 30110661
TI  - Recent developments in green membrane-based extraction techniques for
      pharmaceutical and biomedical analysis.
AB  - Monitoring of target analytes (e.g., pharmaceuticals, endogenous compounds)
      present in biological samples usually requires a preliminary step toward analyte
      isolation from surrounding matrix and enrichment for trace analysis. Evident
      developments have been recently made to introduce novel "green" analytical
      approaches (which keep the requirements of Green Analytical Chemistry - GAC)
      being effective, economical, eco-friendly, and amenable to hyphenated analytical
      instrumentations. Modern membrane-based extraction techniques provide the smart
      options against classical sample preparations e.g., liquid-liquid extraction
      (LLE).These approaches are more stable and allow trace determination of analytes
      in complex matrices (e.g., biological samples), with high extraction recovery and
      selectivity. Simultaneously, drawbacks of LLE such as large consumption of
      organic solvents and the need for tedious handling are eliminated. This paper
      thoroughly overviews important features and applications of membrane- based
      extraction techniques with special focus on pharmaceutical and biomedical
      analysis since 2013. Different driving forces of mass transfer across the
      membrane were summarized and membrane-based extraction techniques were described
      along with their advantages/disadvantages as well.

PMID- 30110662
TI  - High-definition transcranial direct current simulation (HD-tDCS) for persistent
      auditory hallucinations in schizophrenia.
AB  - Conventional transcranial Direct Current Stimulation (tDCS) has been reported to
      alleviate persistent auditory hallucinations (AH) in schizophrenia as an add-on
      intervention. High-Definition tDCS (HD-tDCS), an optimized form of tDCS, has the
      potential for more focalized neuromodulation. In this study, add-on HD-tDCS (5
      days twice daily session with 2-mA cathodal current on left temporo-parietal
      junction) using 4 * 1 ring montage significantly reduced persistent AH (t = 3.6;p
      < 0.01) in schizophrenia patients (N = 19). Add-on HD-tDCS has promising
      potential to treat persisting AH in schizophrenia. This needs further systematic
      research.

PMID- 30110663
TI  - Anchored phylogenomics unravels the evolution of spider flies (Diptera,
      Acroceridae) and reveals discordance between nucleotides and amino acids.
AB  - The onset of phylogenomics has contributed to the resolution of numerous
      challenging evolutionary questions while offering new perspectives regarding
      biodiversity. However, in some instances, analyses of large genomic datasets can
      also result in conflicting estimates of phylogeny. Here, we present the first
      phylogenomic scale study of a dipteran parasitoid family, built upon anchored
      hybrid enrichment and transcriptomic data of 240 loci of 43 ingroup acrocerid
      taxa. A new hypothesis for the timing of spider fly evolution is proposed,
      wielding recent advances in divergence time dating, including the fossilized
      birth-death process to show that the origin of Acroceridae is younger than
      previously proposed. To test the robustness of our phylogenetic inferences, we
      analyzed our datasets using different phylogenetic estimation criteria, including
      supermatrix and coalescent-based approaches, maximum-likelihood and Bayesian
      methods, combined with other approaches such as permutations of the data,
      homogeneous versus heterogeneous models, and alternative data and taxon sets.
      Resulting topologies based on amino acids and nucleotides are both strongly
      supported but critically discordant, primarily in terms of the monophyly of
      Panopinae. Conflict was not resolved by controlling for compositional
      heterogeneity and saturation in third codon positions, which highlights the need
      for a better understanding of how different biases affect different data sources.
      In our study, results based on nucleotides were both more robust to alterations
      of the data and different analytical methods and more compatible with our current
      understanding of acrocerid morphology and patterns of host usage.

PMID- 30110664
TI  - Sediment in-situ bioremediation by immobilized microbial activated beads: Pilot
      scale study.
AB  - A field study was carried out to investigate the sediment in-situ bioremediation
      by adding microbial activated beads. In this work, Calcium carbonate, silicon
      dioxide, activated carbon powder, attapulgite powder, sodium alginate, microbial
      liquid and polyvinyl alcohol were utilized to make the immobilized microbial
      activated beads. Field experiment results showed that the removal rate of NH4+-N,
      TN and COD in overlying water reached about 61.8%, 87.5% and 87.1%, respectively.
      The initial concentration of NH4+-N, TN and COD was 159 mg/L, 6.24 mg/L and 7.28
      mg/L, whereas and the final concentration was 58 mg/L, 0.78 mg/L and 0.94 mg/L
      when water temperature, DO, pH and C/N ratio were 25-30  degrees C, 2-3 mg/L, 7.0
      8.0 and 10-15, respectively. Moreover, under optimal temperature condition (25-30
      degrees C), the removal rate of TOC, TN, heterotrophic bacteria and sulfur
      bacteria in the river sediment reached to 46.5%, 50.7%, 39.2% and 73.2%,
      respectively.

PMID- 30110665
TI  - What genome-wide association studies reveal about the association between
      intelligence and mental health.
AB  - Intelligence, as measured by standardised tests of cognitive function, such as IQ
      type tests, is predictive of psychiatric diagnosis and psychological wellbeing.
      Using genome-wide association study (GWAS) data, a measure of the shared genetic
      effect across traits, can be quantified; because this can be done across samples,
      the confounding effects of psychiatric diagnosis do not influence the magnitude
      of these relationships. It is now known that there are genetic effects that act
      across intelligence and psychiatric diagnoses, which provide a partial
      explanation for the phenotypic link between intelligence and mental health.
      Potential causal effects between intelligence and mental health have been
      identified, and the regions of the genome responsible for some of these cross
      trait associations have begun to be characterised.

PMID- 30110666
TI  - Bioaugmentation of membrane bioreactor with Achromobacter denitrificans strain
      PR1 for enhanced sulfamethoxazole removal in wastewater.
AB  - Achromobacter denitrificans strain PR1, previously found to harbour specific
      degradation pathways with high sulfamethoxazole (SMX) degradation rates, was
      bioaugmented into laboratory-scale membrane bioreactors (MBRs) operated under
      aerobic conditions to treat SMX-containing real domestic wastewater. Different
      hydraulic retention times (HRTs), which is related to reaction time and loading
      rates, were considered and found to affect the SMX removal efficiency. The
      availability of primary substrates was important in both bioaugmented and non
      bioaugmented activated sludge (AS) for cometabolism of SMX. High HRT (24 h)
      resulted in low food to microorganism ratio (F/M) and low SMX removal, due to
      substrate limitation. Decrease in HRT from 24 h to 12 h, 6 h and finally 4 h led
      to gradual increases in primary substrates availability, e.g. organic compounds
      and ammonia, resulted in increased SMX removal efficiency and degradation rate,
      and is more favorable for high-rate wastewater treatment processes. After
      inoculation into the MBRs, the bioaugmentation strain was sustained in the
      reactor for a maximum of 31 days even though a significant decrease in abundance
      was observed. The bioaugmented MBRs showed enhanced SMX removal, especially under
      SMX shock loads compared to the control MBRs. The results of this study indicate
      that re-inoculation is required regularly after a period of time to maintain the
      removal efficiency of the target compound.

PMID- 30110667
TI  - Towards a new model for the governance of the Weerribben-Wieden National Park.
AB  - The paper focuses on the governance of the Dutch national park Weerribben-Wieden
      and its ability to foster ecological resilience in the face of climate change and
      human disturbances. The study highlights the role of various characteristics of
      the institutional context of governance in which resilience-relevant decisions
      are prepared, taken and implemented as referenced by an assessment of the
      governance context. The relevance of such an assessment is found in the frequent
      institutional changes in nature policy. This paper examines how care for the
      resilience in an area is supported by the governance context, given the major
      recent restructurings. The drastic changes in nature policy in the Netherlands
      include national government withdrawing from their central role and
      decentralising the authority for nature tasks to the provinces. Subsequently, the
      province has also withdrawn itself in the Weerribben-Wieden case and
      decentralised nature tasks to the municipality. So, in our research case, the
      'take home message' relates to the impacts of decentralisation in different
      'sizes'. Institutional change by decentralisation does not come in 'one size',
      but rather in a multiform phenomenon of layers and aspects. The governance
      assessment tool was used to analyze the consequences of this decentralisation for
      the processes in which resilience measures are implemented in various degrees and
      interactions. Decentralisation without balanced problem perspectives and goals,
      without an integral approach towards the park's resilience, and without adequate
      strategies and instruments, most likely leads to a lengthy transition process
      with uncertain outcomes. The study concludes that institutional changes in this
      case restricted adaptiveness of governance towards resilience and has diminished
      a sense of responsibility for the maintenance of the national park resources.

PMID- 30110668
TI  - Pragmatic abilities in multiple sclerosis: The contribution of the temporo
      parietal junction.
AB  - Recent studies showed that multiple sclerosis (MS) patients might experience
      communicative deficits, specifically in pragmatics (i.e., the ability to
      integrate the context-dependent aspects of language). A crucial region for
      pragmatics is the temporo-parietal junction, in particular the so-called
      Geschwind's area (GA), which is involved in high-level language processes,
      including the comprehension of narratives, metaphor, and irony. We evaluated the
      relationship between pragmatic abilities, measured through the Assessment of
      Pragmatic Abilities and Cognitive Substrates (APACS) test, and the functional
      connectivity (FC) of the bilateral GAs, assessed through a seed-based analysis of
      Resting-State fMRI in patients with MS. A positive correlation was observed
      between APACS scores and the FC for both the right and the left GA and the
      paracingulate cortex. Our findings suggest that the brain FC for social
      communication involves connections extending over both hemispheres, including
      right and left GAs and right and left paracingulate cortex, possibly impaired in
      patients with MS. This study offers preliminary evidence for future researches
      enrolling also a control sample to explore the involvement of GA in pragmatics in
      neurological disorders as well as in healthy conditions.

PMID- 30110669
TI  - Impact of presence of excipients in drug analysis in fed-state gastric
      biorelevant media.
AB  - In this study, the influence of the presence of excipients in sample preparation
      and clean-up steps required prior to drug analysis in milk-based media which
      simulate the in vivo properties of the fed state stomach was investigated. 15
      excipients, normally present in solid dosage forms of five APIs tested (atenolol,
      paracetamol, furosemide, nifedipine and propafenone hydrochloride) were mixed
      (one at a time) with the active pharmaceutical ingredient of interest either via
      vortexing, co-grinding or shaking of the physical mixture and dissolved in Fed
      State Simulated Gastric Fluid (FeSSGF). The objective of the study was the
      assessment of the extraction efficiency of three protein precipitation protocols
      (using MeOH, AlphaCN and 10% w/v TCA), typically used in drug analysis, in milk
      based biorelevant media in the presence of the excipients. The mixing technique,
      fat content of the medium and excipient and solvent effects were investigated.
      The efficiency of three different protein precipitation reagents in drug
      extraction when dissolved as API:excipient mixtures in the fed-state medium was
      compared against the equivalent drug amount recovered in the absence of the
      excipient in FeSSGF. Most excipients had a significant negative effect (p < 0.05)
      on drug recovery in the milk-based medium as indicated by the multiple linear
      regression (MLR) analysis performed. For magnesium stearate and HPMC, the %
      recovery values were the lowest in four out of the five drugs studied, with a
      range of 10-100% depending on the API, mixing technique and protein precipitation
      protocol selected. The negative excipient-dependent effect was more profound in
      nifedipine and propafenone hydrochloride, the most lipophilic compounds of the
      study. Acetonitrile was the most effective extraction reagent for most drugs in
      the presence of excipients, followed by methanol and 10% w/v trichloroacetic
      acid. Data analysis also revealed a dependence of the extraction method
      efficiency on the medium lipid content. Application of the above extraction
      protocols in commercially available formulations highlighted the need for
      assessment of the effect of excipients in extraction efficiency, before
      transferring the method directly to dissolution studies of formulations in milk
      based fed gastric media. In conclusion, the presence of excipients and the
      selection of protein precipitation protocol are parameters which can affect
      significantly the efficiency of protein precipitation when FeSSGF is used as
      dissolution medium and need to be taken into consideration when developing a
      quantitative method based on the above sample clean-up technique.

PMID- 30110670
TI  - When to Stop Eculizumab in Complement-Mediated Thrombotic Microangiopathies.
AB  - The terminal complement-inhibitor eculizumab has dramatically changed the
      management of patients with atypical hemolytic uremic syndrome (aHUS), and has
      also shown promise for treating certain forms of secondary HUS (sHUS), including
      that caused by drugs and solid-organ/hematopoietic stem cell transplant. While
      effective, eculizumab is costly and inconvenient. In this review, we evaluate the
      literature on eculizumab cessation in these diseases to better inform clinicians
      who consider stopping therapy. Reported relapse rates in aHUS after stopping
      eculizumab are as high as 30%, suggesting indefinite therapy is reasonable and
      that patients who choose to stop should be closely monitored. In sHUS, relapse is
      rare, justifying short courses of eculizumab.

PMID- 30110671
TI  - Changes in Total Protein Concentration Due to Fluid Removal During and Shortly
      after Hemodialysis.
AB  - BACKGROUND: Changes in plasma volume during hemodialysis are complex and have
      been shown to depend on the rate of fluid removal and the degree of fluid
      overload. We examined changes in total protein concentration during and shortly
      after a dialysis treatment in archived data from the HEMO study. METHODS: During
      follow-up months 4 and 36 of the HEMO study, additional blood samples were
      obtained during a typical dialysis session at 30 and 60 min after dialysis. In
      315 studies from 282 patients where complete data were available, we calculated
      the concentration change in total protein and compared it to the modeled change
      in both total body water and extracellular fluid space as derived from 2-pool
      urea kinetic modeling. RESULTS: The mean postdialysis modeled urea volume (V) was
      31.1 +/- 6.18 L. Mean fluid removal was 2.76 +/- 1.27 kg, over a session length
      of 207 +/- 28 min. The ratio of predialysis V to postdialysis V averaged 1.090 +/
      0.040. The mean TP ratios (post/pre) at 0, 30, and 60 min postdialysis averaged
      1.121 +/- 0.070 (SD), 1.091 +/- 0.090, and 1.091 +/- 0.086. The dialysate to
      serum sodium gradient, studied in a different group of treatments where this
      information was available, had no impact on these findings, nor did the length of
      the interdialytic interval. CONCLUSIONS: On average, after equilibration, the
      change in plasma volume due to fluid removal is similar to the modeled change in
      total body water (urea space), irrespective of dialysate to serum sodium
      gradient. This supports previous observations that during dialysis with
      ultrafiltration, plasma volume contracts to a lesser degree than the interstitial
      volume and that some fluid may be removed from spaces other than the
      extracellular fluid.

PMID- 30110672
TI  - Clinic-Pathologic Features and Renal Outcome of Fabry Disease: Data from a
      Chinese Cohort.
AB  - BACKGROUND: Fabry disease (FD) with life-threatening complications occurs as a
      result of organ damage in kidneys, heart, and brain. Only a few studies,
      especially from Asia, report their long-term outcome. METHODS: In this
      monocentric study, patients with Fabry nephropathy confirmed by renal biopsy were
      clinically investigated in a comprehensive manner. The clinic-pathological
      features, progression, and risk factors for the outcome were analyzed. RESULTS:
      Thirty-one patients were recruited, after median 62 months (range 8-156 months)
      follow-up, 23 of them had stable renal function while 8 underwent renal function
      deterioration. Frequent presenting symptoms included acroparesthesia (58.1%),
      edema (51.6%), hypo- or anhidrosis (38.7%), and angiokeratoma (32.3%). Left
      ventricular hypertrophy was present in 62.5% patients with renal function
      deterioration and 17.4% patients with stable renal function (p = 0.03). The renal
      cumulative survival rate of all patients was 64.5% in 10 years. Mainz Severity
      Score Index (MSSI) and segmental sclerosis are independent predictive factors for
      a more rapid progression of Fabry nephropathy. The receiver operating
      characteristic analysis demonstrated that the area under the curve for the
      prediction of renal function progression on the basis of MSSI and segmental
      sclerosis levels in patients with FD was 0.845 and 0.780, respectively. MSSI
      score >=18 or segmental sclerosis >=3.9% in patients with FD positively
      correlated with poor renal prognosis. CONCLUSIONS: FD's clinical manifestations
      are heterogeneous and nonspecific. The -10-year cumulative renal survival rate
      was low in Chinese patients. MSSI score and segmental sclerosis levels predict
      the renal prognosis of patients with FD sensitively.

PMID- 30110673
TI  - Association between Atopic Dermatitis and the Metabolic Syndrome: A Systematic
      Review.
AB  - Atopic dermatitis (AD) may be associated with the metabolic syndrome and by that
      carry an increased risk of cardio-vascular disease. Our objective was to provide
      an update on current knowledge of the association between AD and metabolic
      syndrome, including each component of the metabolic syndrome. A systematic
      literature review was performed to identify studies investigating the association
      between metabolic syndrome and AD from PubMed, Embase, and the Cochrane Library
      in accordance with the Preferred Reporting Items for Systematic reviews and Meta
      Analyses (PRISMA) guidelines. A total of 14 studies, investigating the
      association between AD and the metabolic syndrome or AD and components of
      metabolic syndrome fulfilled the inclusion criteria and were included. It seems
      unlikely that the association between AD and metabolic syndrome is causal.
      However, women with AD tended to have components of metabolic syndrome more often
      than women without AD. There was a positive association between AD and central
      obesity measured as waist circumference, and this association was stronger for
      women than men. Despite conflicting results regarding hypertension, the
      association between hypertension and AD also appeared stronger for women. On the
      other hand, the association between AD and hyperglycemia appears unlikely, and
      the association between AD and cholesterol levels was inconsistent. In
      conclusion, it remains unclear whether AD is a risk factor for metabolic syndrome
      and its components. However, data indicate that central obesity is associated
      with AD and that the association is stronger for women than men.

PMID- 30110675
TI  - Obstructive Sleep Apnea Increases Sudden Cardiac Death in Incident Hemodialysis
      Patients.
AB  - BACKGROUND: Mortality in end-stage renal disease (ESRD) occurs predominantly from
      cardiovascular disease (CVD) and sudden cardiac death (SCD). Obstructive sleep
      apnea (OSA) is characterized by periodic airflow limitation associated with sleep
      arousal and oxygen desaturation and is prevalent in patients with ESRD. Whether
      OSA increases the risk for SCD, cardiovascular and all-cause mortality among
      hemodialysis patients remains unknown. METHODS: In a prospective cohort of 558
      incident hemodialysis patients, we examined the association of OSA with all-cause
      mortality, cardiovascular mortality, and SCD using Cox proportional hazards
      models controlling for traditional CVD risk factors. RESULTS: Sixty-six incident
      hemodialysis patients (12%) had OSA. Mean age (56 years) and percentage of males
      (56%) were identical in OSA and no-OSA groups. Fewer African Americans had OSA
      than non-African Americans (9 vs. 18%, respectively). Participants with OSA had
      higher body-mass index, Charlson comorbidity score, and left ventricular mass
      index and greater prevalence of diabetes and coronary artery disease. During
      1,080 person-years of follow-up, 104 deaths occurred, 29% of which were
      cardiovascular. OSA was associated with a higher risk of all-cause mortality (HR
      1.90 [95% CI 1.04-3.46]) and cardiovascular mortality (HR 3.62 [95% CI 1.36
      9.66]) after adjusting for demographics and body-mass index. OSA was associated
      with a higher risk of SCD after adjusting for demographics (HR 3.28 [95% CI 1.12
      9.57]) and multiple cardiovascular risk factors. CONCLUSIONS: Incident
      hemodialysis patients with OSA are at increased risk of all-cause and
      cardiovascular mortality and SCD. Future studies should assess the impact of
      screening for OSA and OSA-targeted interventions on mortality in ESRD.

PMID- 30110676
TI  - CD56 for Multiple Myeloma: Lack of CD56 May Be Associated with Worse Prognosis.

PMID- 30110674
TI  - Uric Acid as a Predictor of Immunoglobulin A Nephropathy Progression: A Cohort
      Study of 1965 Cases.
AB  - BACKGROUND: The role of serum uric acid (SUA) level in the progression of
      Immunoglobulin A nephropathy (IgAN) remains controversial. METHODS: In a cohort
      of 1,965 cases with biopsy-proven IgAN, we examined the associations of SUA
      concentration with the primary outcome of a composite of all-cause mortality or
      kidney failure (defined as a reduction of estimated glomerular filtration rate
      [eGFR] by 40% from baseline, requirements for dialysis and transplantation), or
      the outcome of kidney failure alone, assessed using Cox and logistic regression
      models, respectively, with adjustment for confounders. RESULTS: At baseline, the
      mean age was 33.37 +/- 11.07 years, eGFR was 101.30 +/- 30.49 mL/min/1.73 m2, and
      mean uric acid level was 5.32 +/- 1.76 mg/dL. During a median of 7-year follow
      up, 317 cases reached the composite outcome of all-cause mortality (5 deaths) or
      kidney failure (36 cases of dialysis, 5 cases of renal transplantation, and 271
      cases with reduction of eGFR by 40% from baseline). After adjustment for
      demographic and IgAN specific covariates and treatments, a higher quartile of
      uric acid was linearly associated with an increased risk of the primary outcome
      (highest versus lowest quartile, hazard ratio [HR] 2.39; 95% CI 1.52-3.75) and
      kidney failure (highest versus lowest quartile, HR 2.55; 95% CI 1.62-4.01) in the
      Cox proportional hazards regression models. In the continuous analysis, a 1 mg/dL
      greater uric acid level was associated with 16% increased risk of primary outcome
      (HR 1.16, 95% CI 1.07-1.25) and 17% increased risk of kidney failure (HR 1.17,
      95% CI 1.08-1.27), respectively, in the fully adjusted model. The multivariate 
      logistic regression analyses for the sensitive analyses drew consistent results.
      In the subgroup analyses, significant interactions were detected that patients
      with mean arterial pressure (MAP) < 90 mm Hg or mesangial hypercellularity had a
      higher association of SUA with the incidence of the primary outcome than those
      with MAP >=90 mm Hg or those without mesangial hypercellularity respectively.
      Hyperuricemia was not significantly associated with the risk of developing the
      primary outcome in elder patients (>=32 years old), patients with eGFR < 90
      mL/min or with tubular atrophy/interstitial fibrosis. CONCLUSIONS: SUA level may
      be positively associated with the progression of IgAN. It was noticeable that the
      association of hyperuricemia with IgAN progression was less significant in
      patients with elder age, lower eGFR, or tubular atrophy/interstitial fibrosis,
      which may be due to some more confounders in association with the IgA progression
      in these patients. Future prospective studies are warranted to confirm these
      findings and to investigate the underlying mechanisms.

PMID- 30110677
TI  - Kidney Protection Effect of Ginsenoside Re and Its Underlying Mechanisms on
      Cisplatin-Induced Kidney Injury.
AB  - BACKGROUND/AIMS: Cisplatin (CDDP) was the first platinum-containing anti-cancer
      drug. However, CDDP causes nephrotoxicity as a side effect, which limits its
      clinic application. The aim of this study was to investigate the renoprotective
      effect of ginsenoside Re (G-Re) in a murine model of CDDP-induced acute kidney
      injury. METHODS: Male ICR mice were divided into 4 groups. G-Re was administered
      to the mice by oral gavage once a day at a dose of 25 mg/kg for 10 days. On the
      7th day, a single injection of CDDP (25 mg/kg) was given at 1 h after G-Re
      treatment. RESULTS: CDDP administration resulted in renal dysfunction, as
      evidenced by an increase in the serum levels of creatinine and urea nitrogen.
      Oxidative stress in the CDDP group was reflected by an increase of
      malondialdehyde and a depletion of reduced glutathione and catalase in renal
      tissue. These findings were supported by increased 4-hydroxynonenal expression,
      which was significantly reduced by G-Re. Simultaneously, the overexpression of
      cytochrome P450 E1 was inhibited. G-Re inhibited the inflammatory response by the
      reduction of the protein expression of cyclooxygenase-2 and inducible nitric
      oxide synthase. Furthermore, CDDP increased the expression of Bax and decreased
      Bcl-2 expression in renal tissue. Hematoxylin and eosin, Hoechst 33258, and TUNEL
      staining also confirmed the presence of acute tubular necrosis and apoptosis. G
      Re significantly decreased the levels of indicators of renal dysfunction,
      inflammatory cytokines, apoptosis, and malondialdehyde in the kidney and also
      significantly attenuated the histopathological changes associated with acute
      renal failure. CONCLUSIONS: Collectively, the results of this study suggest that
      the nephroprotective potential of G-Re may, in part, be related to its anti
      oxidant, anti-inflammatory, and anti-apoptotic effects.

PMID- 30110681
TI  - Characterization and Outcomes of Disease Progression in 52 Patients Treated with
      BRAF-V600 + MEK Inhibitors for Advanced Melanoma.
AB  - BACKGROUND: Combined treatment with BRAF-V600 and MEK inhibitors has
      significantly improved progression-free and overall survival of patients with
      BRAF-mutated melanoma. Pattern of disease progression and outcomes in patients
      have not been fully characterized. METHODS: We conducted a single-center,
      retrospective, descriptive analysis of a cohort of 52 patients treated with BRAF
      V600 + MEK inhibitors for advanced melanoma over a 12-month period. The aim of
      this study was to characterize disease progression, defined as metastatic
      pattern, disease kinetics, and response to subsequent therapies, in melanoma
      patients treated with BRAF-V600 + MEK inhibitors. RESULTS: Disease progression
      was observed in 31/52 (59.6%) patients treated with BRAF-V600 + MEK inhibitors.
      Relapse of melanoma involved the CNS for 22/31 (70.9%) patients with disease
      progression, including 18/31 (58%) patients who had exclusive intracranial
      metastases. Sixteen patients died from disease progression. Among the 31 patients
      who had disease progression, the median time until a relapse was 8 months, and
      the median survival time after disease progression was 2 months. CONCLUSION: Our
      study shows that, for patients treated with BRAF-V600 + MEK inhibitors who lose
      response, disease progression was aggressive and had poor outcomes. Most patients
      had CNS metastases and low rates of therapeutic response to any subsequent
      therapy.

PMID- 30110678
TI  - HepaRG-Progenitor Cell Derived Hepatocytes Cultured in Bioartificial Livers Are
      Protected from Healthy- and Acute Liver Failure-Plasma Induced Toxicity.
AB  - BACKGROUND/AIMS: For applicability of cell-based therapies aimed at the treatment
      of liver failure, such as bioartificial livers (BALs) and hepatocyte
      transplantation, it is essential that the applied hepatocytes tolerate exposure
      to the patient plasma. However, plasma from both healthy donors and acute liver
      failure (ALF) patients is detrimental to hepatocytes and hepatic cell lines, such
      as HepaRG. We aimed to elucidate the underlying mechanisms of plasma-induced
      toxicity against HepaRG cells in order to ultimately develop methods to reduce
      this toxicity and render HepaRG-BAL treatment more effective. METHODS:
      Differentiated HepaRG cells cultured in monolayers and laboratory-scale BALs were
      exposed to culture medium, healthy human plasma, healthy porcine plasma and ALF
      porcine plasma. Healthy human plasma was fractionated based on size- and
      polarity, albumin depleted and heat treated to characterize the toxic fraction.
      The cells were assessed for viability by total protein content and trypan blue
      staining. Their hepatic differentiation was assessed on transcript level through
      qRT-PCR and microarray analysis, and on functional level for Cytochrome P450 3A4
      activity and ammonia elimination. Mitochondrial damage was assessed by JC-1
      staining and mitochondrial gene transcription. RESULTS: Sixteen hours of healthy
      human plasma exposure did not affect viability, however, hepatic gene-transcript
      levels decreased dramatically and dose-dependently within four hours of exposure.
      These changes were associated with early NF-kB signaling and a shift from
      mitochondrial energy metabolism towards glycolysis. Healthy human plasma-toxicity
      was associated with the dose-dependent presence of heat-resistant, albumin-bound
      and (partly) hydrophobic toxic compound(s). HepaRG cells cultured in BALs were
      partially protected from plasma-toxicity, which was mainly attributable to medium
      perfusion and/or 3D configuration applied during BAL culturing. The detrimental
      human plasma effects were reversible in BAL-cultured cells. Porcine ALF-plasma
      elicited mitotoxicity additional to the basal detrimental effect of porcine
      healthy plasma, which were only partially reversible. CONCLUSION: A specific
      fraction of human plasma reduces hepatic differentiation of HepaRG cultures, in
      association with early NF-kappaB activation. In addition, ALF-plasma elicits
      mitotoxic effects. These findings allow for a targeted approach in preventing
      plasma-induced cell damage.

PMID- 30110680
TI  - Serum Creatinine and Chronic Kidney Disease-Epidemiology Estimated Glomerular
      Filtration Rate: Independent Predictors of Renal Replacement Therapy following
      Cardiac Surgery.
AB  - BACKGROUND: Most studies evaluating predictors of renal replacement therapy (RRT)
      following cardiac surgery use arbitrary defined limits of preoperative serum
      creatinine. The aim of this study was to evaluate the effect of preoperative
      renal function using either estimated-glomerular filtration rate (eGFR) derived
      using Chronic Kidney Disease-Epidemiology (CKD-EPI) or serum creatinine alone as
      a predictor for RRT after cardiac surgery. METHODS: In this prospective cohort
      study, baseline, intraoperative, and postoperative data of all patients who
      underwent an elective, urgent, or emergency cardiac surgery between 2012 and 2016
      in a single center were analyzed in order to identify multivariate parameters
      determining the need for RRT after surgery. For preoperative renal function, we
      used serum creatinine levels and eGFR-derived CKD-EPI equation. We also divided
      our cohort into eGFR groups following the thresholds of the currently proposed
      CKD classification. RESULTS: From the 1,614 patients (mean age: 65.4 +/- 10.6
      years; male: 77.6%) that constituted the study population, 42 (2.6%) underwent
      RRT postoperatively. EUROSCORE II, cardiopulmonary bypass time, cross clamp time,
      red blood cell (RBC) units transfused, type and urgency of surgery, combined/non
      combined operation, peripheral vascular disease, heart failure, chronic
      obstructive pulmonary disease, dyslipidemia, and preoperative renal function were
      all univariately associated with RRT use. Multivariate regression with bootstrap
      utilization indicated that CKD-EPI eGFR (OR 0.979; 95% CI 0.956-0.998), heart
      failure with the New York Heart Association class >=2 (OR 4.695; 95% CI 1.756
      14.061) and RBC units transfused (OR 1.287; 95% CI 1.081-1.850) were
      independently associated with RRT need. When serum creatinine (OR 2.920, 95%
      CI1.056-8.074) was used in the model, the associations with RRT were also
      significant. CONCLUSION: Preoperative renal function, defined by serum creatinine
      or eGFR by CKD-EPI, NYHA class II-IV, and the number of blood units transfused
      were all independent predictors of RRT postoperatively.

PMID- 30110679
TI  - Increased Cellular Levels of MicroRNA-9 and MicroRNA-221 Correlate with Cancer
      Stemness and Predict Poor Outcome in Human Breast Cancer.
AB  - : Background /Aims: Recent studies of microRNA (miRNA) involvement in
      tumorigenesis have indicated the critical role of these non-coding small RNAs in
      malignant transformation, but the prognostic role, if any, of miRNAs in breast
      cancer remains undetermined. Therefore, we assessed the prognostic significance
      of microRNA-9 (miR-9) and miR-221 in breast cancer toward the goal of
      understanding the contribution(s) of these miRNAs to cancer cell stemness.
      METHODS: The level of each of miR-9 and miR-221 in 206 paired laser capture
      microdissected tumor cells and non-tumor cells was determined by quantitative
      reverse transcription-PCR (qRT-PCR). The relationship between the miRNA signature
      and clinicopathological data and prognosis of breast cancer was assessed.
      Identification of a stem cell-enriched side population was achieved with
      fluorescence-activated cell sorting and a sphere-forming assay. Wound healing,
      Boyden chamber assays, and western blotting were used to study the contribution
      of each miRNA to tumor cell migration and invasion. RESULTS: We found that
      induction of miR-9 and miR-221 mimics conferred side-population cells to form
      spheroidal tumor colonies in suspension culture that maintained the mesenchymal
      stem-cell potential in non-invasive MCF-7 breast cancer cells. In contrast,
      knockdown of both miR-9 and miR-221 in invasive MDA-MB-231 breast cancer cells
      dramatically decreased the number of side-population colonies with stem cell-like
      potency, which reduced the capacity for tumor-cell renewal, invasion, and
      migration. Clinically, the mean proportion of miR-9- or miR-221-overexpressing
      cells was significantly greater in tumor cells compared with non-tumor cells (P <
      0.05). Increased levels of miR-9 and miR-221 in breast tissue portended a
      significantly elevated risk of progression to malignancy with respect to larger
      tumor size, poor differentiation, late-stage evolution, lymph-node metastasis (P
      < 0.05), and lower overall survival (Ptrend = 0.017; eight-year follow-up).
      CONCLUSION: Our findings provide strong evidence that miR-9 and miR-221 can
      enhance the generation of cancer stem cells to yield an invasive phenotype and
      that overexpression of these miRNAs predicts a poor outcome for breast cancer
      patients.

PMID- 30110682
TI  - Identification of Competing Endogenous RNA Regulatory Networks in Vitamin A
      Deficiency-Induced Congenital Scoliosis by Transcriptome Sequencing Analysis.
AB  - BACKGROUND/AIMS: Congenital scoliosis (CS) is a result of anomalous development
      of vertebrae and is frequently associated with somitogenesis malformation.
      Although noncoding RNAs (ncRNAs) have been recently determined to be involved in
      the pathogenesis of CS, the competing endogenous RNA (ceRNA) regulatory networks
      in CS remain largely unknown. METHODS: Sequencing was conducted to explore the
      ncRNA expression profiles in rat embryos (gestation day 9) following vitamin A
      deficiency (VAD) (n = 9 for the vitamin A deficiency-induced congenital scoliosis
      (VAD-CS) group and n = 4 for the control group). Real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) was conducted to verify the expression levels
      of selected mRNAs, long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and
      microRNAs (miRNAs). Bioinformatics analysis was used to discover the possible
      relationships and functions of the ceRNAs. RESULTS: A total of 749 mRNAs, 56
      miRNAs, 685 lncRNAs, and 70 circRNAs were identified to have significantly
      different expression levels in the two groups. Wnt, PI3K-ATK, FoxO, EGFR, and
      mTOR were found to be the most significant pathways involved in VAD-CS
      pathogenesis. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of CS were
      built, and the gene expression mechanisms regulated by ncRNAs were unveiled via
      the ceRNA regulatory networks. CONCLUSION: We comprehensively identified ceRNA
      regulatory networks of embryonic somite development in VAD-CS as well as revealed
      the contribution of different ncRNA expression profiles. Our data demonstrate the
      association between mRNAs and ncRNAs in the pathogenic mechanism of CS.

PMID- 30110684
TI  - Tryptophan and Kynurenine Metabolites: Are They Related to Depression?
AB  - BACKGROUND: Some previous studies found decreased concentrations of L-tryptophan
      (TRY) and increased L-kynurenine (KYN), or its metabolites, in the body fluids of
      subjects with major depressive disorder (MDD), sometimes in association with
      suicidal behavior. Such changes might indicate a shift of TRY away from serotonin
      production, possibly via the effects of inflammatory peptides which activate
      indoleamine-2,3-dioxygenase. However, these findings have been inconsistent and
      require replication. METHODS: We used sensitive liquid-chromatography mass
      spectrometry methods to assay plasma concentrations of TRY, 5-hydroxyindoleacetic
      acid (5-HIAA), and KYN and its metabolites (anthranilic acid and xanthurenic
      acid). We compared 49 hospitalized, depressed subjects diagnosed with MDD (n =
      37) or bipolar disorder (BD, n = 12), with (n = 22) or without (n = 27) previous
      suicide attempts, to 78 healthy, ambulatory controls of similar age and sex
      (total n = 127). FINDINGS: Contrary to expectation, TRY plasma concentrations
      were higher, KYN plasma concentrations were lower, and their ratio much higher in
      depressed subjects, with no relationship to suicidal history. Concentrations of 5
      HIAA and the kynurenine metabolites did not differ between depressed and healthy
      subjects. CONCLUSIONS: These findings are opposite to expectations and not
      consistent with a hypothesized increased conversion from TRY to KYN in depressed
      subjects. In addition, we found no evidence of altered production of serotonin as
      5-HIAA concentration was unchanged. None of the observed changes was associated
      with a history of suicide attempt.

PMID- 30110683
TI  - Ghrelin as a Promising Therapeutic Option for Cancer Cachexia.
AB  - Cachexia is a devastating complication of cancer and an important cause of
      morbidity and mortality and can have a great effect on quality of life, and sense
      of self-esteem. Unfortunately; there is no standard cure available for cancer
      cachexia. Ghrelin; a 28 amino acid orexigenic gut hormone and its mimetics have
      shown potential benefits in reversing the breakdown of protein and weight loss in
      catabolic states like cancer cachexia. Ghrelin has effects on several vital
      pathways in the regulation of appetite, and composition of the body. It increases
      the secretion of growth hormone and reduces energy expenditure. It plays an
      important role in regulation of processes associated with cancer and antagonizing
      protein breakdown in catabolic conditions such as cancer cachexia. Additionally,
      ghrelin has anti-inflammatory, anti-apoptotic and anxiolytic effects.
      Administration of ghrelin for short-term has been found to be well-tolerated and
      safe. These versatile actions of ghrelin and its safety can render it as a
      potentially useful novel therapy for patients with cancer cachexia. However;
      there is a need to generate more evidence to support the use of ghrelin in the
      management of cancer cachexia.

PMID- 30110686
TI  - Whole-Body Plethysmography and Blood Gas Analysis in Patients with Acute
      Myocardial Infarction Undergoing Percutaneous Coronary Intervention.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) and coronary heart
      disease (CHD) often occur together. However, COPD is underdiagnosed among CHD
      patients. OBJECTIVES: This study investigated the prevalence of COPD and relevant
      pulmonary function test (PFT) impairments in patients with acute myocardial
      infarction (AMI). METHODS: Patients undergoing coronary angiography for AMI were
      prospectively included. Body plethysmography, lung diffusing capacity, blood gas
      analysis, and echocardiography were performed. The following patient subgroups
      were compared: with versus without COPD, ST elevation myocardial infarction
      (STEMI) versus non-STEMI (NSTEMI). The prevalence of PFT impairments was also
      recorded. RESULTS: A total of 100 patients (51 with NSTEMI, 49 with STEMI) were
      included. Twenty patients had diagnosed COPD, of whom 15 were diagnosed for the
      first time; 80% of all COPD patients were not receiving COPD therapy. Patients
      with COPD had higher maximum creatine kinase (p = 0.008) and troponin T (p =
      0.054) levels than those without COPD. Hypoxaemia was more common in COPD
      patients (lower oxygen saturation [p = 0.008] and partial pressure of oxygen
      [PaO2] [p = 0.005]). PaO2 was significantly lower in STEMI compared with NSTEMI
      (p = 0.017). Independent of a COPD diagnosis, 65 patients had relevant PFT
      impairments. CONCLUSIONS: The high prevalence of undiagnosed COPD and relevant
      pulmonary function impairments in this cohort of patients with AMI, and the fact
      that pulmonary disease was untreated in the majority of COPD patients, highlight
      the importance of a general pulmonary workup of patients with AMI. Furthermore,
      patients with CHD should undergo screening for COPD, given the fact that COPD
      patients had larger infarction size.

PMID- 30110685
TI  - A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and
      Biological Markers in the EMBARC Trial.
AB  - BACKGROUND: One in three clinical trial patients with major depressive disorder
      report symptomatic improvement with placebo. Strategies to mitigate the effect of
      placebo responses have focused on modifying study design with variable success.
      Identifying and excluding or controlling for individuals with a high likelihood
      of responding to placebo may improve clinical trial efficiency and avoid
      unnecessary medication trials. METHODS: Participants included those assigned to
      the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for
      Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used
      to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological
      variables to identify the most robust yet parsimonious features that predicted
      depression severity at the end of the double-blind 8-week trial. Variables
      retained in at least 50% of the 100 imputed data sets were used in a Bayesian
      multiple linear regression model to simultaneously predict the probabilities of
      response and remission. RESULTS: Lower baseline depression severity, younger age,
      absence of melancholic features or history of physical abuse, less anxious
      arousal, less anhedonia, less neuroticism, and higher average theta current
      density in the rostral anterior cingulate predicted a higher likelihood of
      improvement with placebo. The Bayesian model predicted remission and response
      with an actionable degree of accuracy (both AUC > 0.73). An interactive
      calculator was developed predicting the likelihood of placebo response at the
      individual level. CONCLUSION: Easy-to-measure clinical, behavioral, and
      electrophysiological assessments can be used to identify placebo responders with
      a high degree of accuracy. Development of this calculator based on these findings
      can be used to identify potential placebo responders.

PMID- 30110688
TI  - The Positive Effect of Sialendoscopy with Irrigation Lavage for Sialadenitis
      without Sialolithiasis or Stenosis.
AB  - AIMS: The aim of the study was to evaluate different irrigation solutions during
      sialendoscopy to reduce complaints caused by sialodochitis. METHODS: The
      investigators designed and implemented a retrospective study composed of 94
      patients with sialodochitis but no sialolithiasis or relevant stenosis of the
      salivary duct system. Three different irrigations (normal saline, cortisone
      single-shot, and cortisone) were used. After the sialendoscopy, the patients were
      asked about the current status of the affected salivary gland, and the quantity
      and quality of the gland swelling/inflammation over a follow-up period of 11.6
      months (6-24 months). RESULTS: At the time of follow-up, 41 patients (43.6%) no
      longer had any complaints with the salivary gland in question. In 75.5% of the
      patients, a satisfying result was achieved. In total, only 3 patients needed
      submandibulectomy in the course of the study due to persistent complaints. The
      outcome showed no statistical differences between the mean of the 3 groups (p =
      0.149). CONCLUSION: Sialendoscopy with flushing/lavage seems to be a good
      treatment option for patients with sialodochitis lacking sialolithiasis. The
      results of this study suggest that the type of irrigation used during
      sialendoscopy seems to be secondary.

PMID- 30110687
TI  - Synchronous Primary Central Nervous System and Pulmonary Lymphoma in a 7-Year-Old
      Female with Unspecified T-Cell Immunodeficiency.
AB  - Primary central nervous system lymphoma (PCNSL) is rare in children with
      immunocompromise as an important risk factor. A 7-year-old girl with unspecified
      T-cell immunodeficiency presented with left-sided weakness and was found to have
      a right-sided frontal lobe mass on imaging. The mass was resected; histopathology
      and molecular studies evidenced diffuse large B-cell lymphoma. Prior chest
      imaging had revealed left upper lobe mass, and repeat chest imaging revealed
      multiple pulmonary nodules, initially concerning for metastasis. Video-assisted
      thoracoscopic surgical wedge resection of the lung mass was performed; the
      molecular profile was distinct from the PCNSL, suggesting synchronous de novo
      lymphomagenesis of brain and pulmonary primaries.

PMID- 30110689
TI  - MR-Guided Laser Interstitial Thermal Therapy for Medically Refractory Lesional
      Epilepsy in Pediatric Patients: Experience and Outcomes.
AB  - INTRODUCTION: MR-guided laser interstitial thermal therapy (MRgLITT) has emerged
      as a safe and effective treatment option for the ablation of epileptic foci. Its
      minimally invasive nature makes it attractive due to decreased morbidity and
      hospital stay. OBJECTIVE: To report the efficacy and safety of MRgLITT as a
      minimally invasive procedure for the ablation of epileptic foci in the pediatric
      population of medically refractory lesional epilepsy. METHODS: A retrospective
      review of patients who underwent MRgLITT via Visualase laser ablation at a single
      pediatric center was performed. Demographic and outcome data were compiled and
      analyzed. RESULTS: Twelve pediatric patients with a total 18 lesions underwent
      MRgLITT procedures between December 2013 and September 2017. Mean age at surgery
      was 11.1 years. Surgical substrates included 4 hypothalamic hamartomas, 3
      periventricular heterotopias, 2 deep focal cortical dysplasias, 2 tuberous
      sclerosis, and 1 mesial temporal sclerosis. Methods of stereotaxis used included
      Leksell frame, BrainLab VarioGuide, ROSA robot guidance, and ClearPoint
      navigation. Mean procedure length was 250 min, and mean length of stay was 1.3
      days. After treatment, 8 patients were seizure free (Engel I, 66.7%), 2 patients
      demonstrated significant improvement (Engel II, 16.7%), and 2 patients showed
      worthwhile improvement (Engel III, 16.7%). One patient developed a left superior
      quadrantanopsia postoperatively. Mean follow-up duration was 10 months.
      CONCLUSION: This study contributes to the sparse literature in this field by
      demonstrating the high efficacy and low morbidity of MRgLITT as a minimally
      invasive method of ablation of epileptic foci in the pediatric population of
      medically refractory lesional epilepsy.

PMID- 30110690
TI  - Update on Endoscopic Third Ventriculostomy in Children.
AB  - Endoscopic third ventriculostomy (ETV) provides a physiological restoration of
      cerebrospinal fluid and a shunt-free option for hydrocephalus children.
      Continuous developments in techniques and instruments have improved ETV as the
      first-line treatment. This paper focuses on the recent advances in surgical
      techniques, instruments, predictive models, imaging tools, and new cohort
      studies. The efficacy, safety, indications, and remaining challenges of ETV are
      discussed. More patients undergo ETV with a better outcome, identifying a new era
      of hydrocephalus treatment. Deeper understanding of ETV will improve a better
      shunt-free survival for pediatric hydrocephalus patients.

PMID- 30110691
TI  - Bronchial Thermoplasty-Induced Acute Airway Effects Assessed with Optical
      Coherence Tomography in Severe Asthma.
AB  - BACKGROUND: Bronchial thermoplasty (BT) is an endoscopic treatment for severe
      asthma targeting airway smooth muscle (ASM) with radiofrequent energy. Although
      implemented worldwide, the effect of BT treatment on the airways is unclear.
      Optical coherence tomography (OCT) is a novel imaging technique, based on near
      infrared light, that generates high-resolution cross-sectional airway wall
      images. OBJECTIVE: To assess the safety and feasibility of OCT in severe asthma
      patients and determine acute airway effects of BT by OCT and compare these to the
      untreated right middle lobe (RML). METHODS: Severe asthma patients were treated
      with BT (TASMA trial). During the third BT procedure, OCT imaging was performed
      immediately following BT in the airways of the upper lobes, the right lower lobe
      treated 6 weeks prior, and the untreated RML. RESULTS: 57 airways were imaged in
      15 patients. No adverse events occurred. Three distinct OCT patterns were
      discriminated: low-intensity scattering pattern of (1) bronchial and (2)
      peribronchial edema and (3) high-intensity scattering pattern of epithelial
      sloughing. (Peri)bronchial edema was seen in all BT-treated airways, and less
      pronounced in only 1/3 of the RML airways. These effects extended beyond the ASM
      layer and more distal than the directly BT-treated areas and were reduced, but
      not resolved, after 6 weeks. Epithelial sloughing occurred in 11/14 of the BT
      treated airways and was absent in untreated RML airways. CONCLUSIONS: Acute BT
      effects can be safely assessed with OCT and 3 distinct patterns were identified.
      The acute effects extended beyond the targeted ASM layer and distal of directly
      BT-treated airway areas, suggesting that BT might also target smaller distal
      airways.

PMID- 30110692
TI  - Assessment of Placental Cortisol Pathway Gene Expression in Term Pregnant Women
      with Anxiety.
AB  - INTRODUCTION: The aim of this study was to expand on this field of work by
      examining, within a cohort of pregnant women with diagnosed clinical anxiety, the
      mRNA expression of a panel of genes associated with the cortisol pathway and
      comparing them to controls. METHODS: Placental samples were obtained from 24
      pregnant women, 12 with a diagnosed anxiety disorder and 12 with no psychiatric
      history, within 30 min of delivery. Differential expression analysis of 85 genes
      known to be involved in glucocorticoid synthesis, metabolism or signalling was
      conducted for the: (1) full sample, (2) those at term without labour (5 cases, 7
      controls) and (3) those at term with labour (7 cases, 5 controls). Correlation
      analyses between gene expression and measures of anxiety and depressive symptom
      severity were also conducted. RESULTS: No robust difference in placental gene
      expression between pregnant women with and without anxiety disorder was found nor
      did we detect robust differences by labour status. However, correlational
      analyses putatively showed a decrease in PER1 expression was associated with an
      increase in anxiety symptom severity, explaining up to 32% of the variance in
      anxiety symptom severity. DISCUSSION: Overall, the strongest correlation was
      found between a decrease in placental PER1 expression and increased anxiety
      scores. Labour status was found to have a profound effect on mRNA expression. The
      placental samples obtained from women following labour produced greater numbers
      of significant differences in mRNA species expression suggesting that in long
      standing anxiety the placenta may respond differently under conditions of chronic
      stress.

PMID- 30110693
TI  - Effect of Celecoxib on Surgical Site Inflammation after Total Knee Arthroplasty:
      A Randomized Controlled Study.
AB  - OBJECTIVE: To evaluate the anti-inflammatory effectiveness of celecoxib and its
      effect on the rehabilitation of joint function after total knee arthroplasty.
      METHODS: 72 patients presented between 2016 and 2017 and were divided into two
      groups. The experimental group was given 200 mg celecoxib twice daily with
      tramadol hydrochloride 50 mg twice daily (as required); the control group was
      given tramadol hydrochloride 50 mg twice daily for 6 weeks from the first day
      after total knee arthroplasty. Skin temperature around the knee was measured 1
      day before surgery, on postoperative days 1 and 3, and at weeks 1, 2, and 6.
      Inflammatory markers (white blood cell count, C-reactive protein, erythrocyte
      sedimentation rate, and interleukin-6) were measured preoperatively, on
      postoperative day 3, and at weeks 1 and 6. Knee Society Score was recorded
      preoperatively and at postoperative weeks 1, 2, and 6. RESULTS: Except for
      preoperative skin temperature, the recorded skin temperatures of the experimental
      group were significantly different compared to those of the control group (p =
      0.001, 0.024, 0.030, 0.041, 0.047, respectively). Levels of C-reactive protein
      were significantly different at the 1st and the 6th week after surgery, differing
      by 19.3 +/- 4.64 mg/L (p < 0.001) and 2.6 +/- 0.92 mg/L (p = 0.006). Levels of
      interleukin-6 showed a significant difference of 6.61 +/- 2.36 pg/mL (p = 0.007)
      at the 1st week after surgery. Until the 6th week after surgery, the erythrocyte
      sedimentation rate in the experimental group and the control group differed by 17
      +/- 4.6 mm/h (p = 0.001). CONCLUSIONS: Celecoxib has a significant inhibitory
      effect on postoperative aseptic inflammation.

PMID- 30110694
TI  - Definition of Late Onset Alzheimer's Disease and Anticipation Effect of Genome
      Wide Significant Risk Variants: Pilot Study of the APOE e4 Allele.
AB  - BACKGROUND/OBJECTIVES: This study aims to investigate the role of apolipoprotein
      E (APOE) e4 influencing the age at onset (AAO) of Alzheimer's disease (AD). In
      AD, the AAO of dementia varies from 40 to 90 years. Usually, AD patients who
      develop symptoms before the age of 65 are considered as early-onset AD (EOAD).
      However, considering the heterogeneity of the AD onset, the definition of late
      onset AD (LOAD) cannot rely on an arbitrary cut-off. Thus, we aim to validate the
      anticipation effect of the APOE e4 allele in LOAD. Methods/Overview: Firstly, the
      optimal number of AAO subgroups was determined using MCLUST for 3 AD samples from
      Italy, Brazil, and from the ADNI consortium. MCLUST selects the best-fitting
      model based on the Bayesian information criterion (BIC), and the ideal cut-off
      for separating early onset from late onset in each sample. Then, when the AAO was
      modeled for each sample, the finite mixture model (FMM) analysis was used to
      analyze the effect of the APOE e4 in determining the risk for anticipated onset
      in LOAD. For the Brazilian sample, the ancestry was incorporated as a covariate.
      The FMM results from the 3 samples were meta-analyzed using METAL. RESULTS: We
      performed the AAO analysis on the APOE e4 in 474 Italian patients enrolled at the
      IRCCS Santa Lucia Foundation in Italy, 135 AD from the Outpatients Reference
      Center for Geriatrics from the Federal University of Minas Gerais in Brazil, and
      376 from the ADNI consortium. Using this distribution model, we found that the
      specific LOAD cut-off was >=64 for the Italian sample, >=67 for the ADNI sample,
      and >=74 for the Brazilian sample. The APOE e4 showed a significant anticipatory
      effect specific for LOAD in all 3 samples. The METAL analysis for the
      anticipatory e4 effect was genome-wide significant when analyzing the LOAD effect
      size under the fixed model (beta = -8.1; p < 0.0001). However, when analyzing
      EOAD there was no genome-wide significant anticipation effect (beta = 1.9244; p =
      0.0219). CONCLUSIONS: This study showed that the mixture analysis can refine the
      ideal cut-off for defining LOAD as a homogeneous genetic entity. We also
      validated the e4 allele anticipatory effect only in LOAD. In summary, the tool
      developed in this study is a sophisticated statistical pipeline to analyze the
      AAO in genome-wide association studies of AD, to find new molecular targets as a
      new line of translational research to foster drug discovery.

PMID- 30110695
TI  - A Pilot Study to Evaluate the Effects of Topically Applied Cosmetic Creams on
      Epidermal Responses.
AB  - Application of exogenous products, such as creams, to the skin can result in
      subclinical changes in selected epidermal functions such as transepidermal water
      loss (TEWL), hydration, redness, and pH; these changes may lead to or contribute
      to irritation. Changes in skin surface inflammatory factors may provide further
      insight into this potential for irritation. The objective of this study was to
      evaluate the changes in epidermal properties and inflammatory mediators after 4
      days of topical application of 2 different polymers formulated in cosmetic
      creams. Ten healthy volunteers (mean age +/- SD: 20.0 +/- 2.4 years) completed
      the study. TEWL, color, and pH were not significantly different after repeated
      application of these polymers. Hydration was significantly lower at sites treated
      with polymer A after 5 days. Significant increases in IL-1alpha, IL-1RA, and IL
      1beta were observed after cream application at sites treated with polymer A. This
      is the first study to apply noninvasive measurements to quantify subclinical
      changes in epidermal properties and inflammatory mediator expression before and
      after the application of a cosmetic product, which will allow for a more enhanced
      safety profile to be achieved.

PMID- 30110697
TI  - Long-Term Outcomes of Full-Fluence and Half-Fluence Photodynamic Therapy for
      Chronic Central Serous Chorioretinopathy.
AB  - PURPOSE: To evaluate the efficacy and safety of full-fluence photodynamic therapy
      (PDT) and half-fluence PDT in chronic central serous chorioretinopathy (CSC).
      PROCEDURES: A retrospective review of CSC patients treated with full-fluence or
      half-fluence PDT for 12 months was performed. Best-corrected visual acuity
      (BCVA), central macular thickness (CMT), neural retinal thickness, subfoveal
      choroidal thickness (SFCT), resolution of subretinal fluid (SRF), and incidence
      of retinal pigment epithelium (RPE) atrophy at 12, 24, and 36 months were
      assessed. RESULTS: Thirty-seven and 30 eyes received full-fluence and half
      fluence PDT, respectively. The BCVA and CMT improved significantly in both the
      full-fluence and half-fluence groups at 36 months, without a significant
      difference between the groups. Both groups showed significant reductions in SFCT
      with full-fluence (416.8-316.8 um) being better overall than half-fluence (409.7
      349.1 um, p = 0.002). All patients achieved complete resolution without
      recurrence after one PDT treatment per eye. A few cases of RPE atrophy occurred,
      which could be correlated to PDT in both groups during the follow-up. CONCLUSION:
      Both treatments were effective and safe in chronic CSC, with significant
      improvements in anatomic and visual parameters, without recurrence of SRF.

PMID- 30110696
TI  - Intravitreous Delivery of Alphab-Crystallin Ameliorates N-Methyl-N-Nitrosourea
      Induced Photoreceptor Degeneration in Mice: An in vivo and ex vivo Study.
AB  - BACKGROUND/AIMS: alphaB -crystallin (alphaBC) belongs to the family of small heat
      shock proteins that are necessary for maintaining oxygen homeostasis. This study
      was designed to explore the possible effects of alphaBC on N-methyl- N
      nitrosourea (MNU) induced retinal degeneration and the underlying mechanisms.
      METHODS: The alphaBC was injected into the vitreous bodies of MNU administered
      mice. The retinal morphology and visual function of experimental animals were
      analyzed by electroretinography (ERG), Spectral domain optical coherence
      tomography (SD-OCT), fundus photographs, optokinetic testing and
      immunohistochemistry assay. RESULTS: Optokinetic behavioural tests and ERG
      examination suggested that the visual impairments of the MNU administered mice
      were ameliorated effectively by alphaBC treatment. OCT analysis showed that the
      major retinal architecture of the MNU administered mice was efficiently rescued
      by alphaBC treatment. Fundus examination suggested that the lesion size of the
      MNU administered mice was decreased by alphaBC treatment. MNU induced
      photoreceptor loss was also mitigated by alphaBC treatment as shown by
      hematoxylin and eosin staining. In particular, the immunostaining study suggested
      that M-cone photoreceptors, rather than the S-cone photoreceptors, were
      preferentially rescued, indicating that the photoreceptor populations have
      different sensitivities to alphaBC. The mechanism study suggested that the anti
      apoptotic, anti-oxidative and neurotrophic function of alphaBC collectively
      contributed to these therapeutic effects. CONCLUSION: Intravitreal delivery of
      alphaBC could alleviate MNU induced photoreceptor degeneration and visual
      impairment. Further refinement of the alphaBC induced protection would afford a
      novel therapeutic strategy for retinitis pigmentosa.

PMID- 30110698
TI  - Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in
      the Retina and Disrupts Subcortical Visual Circuitry in Rodents.
AB  - OBJECTIVE: Interleukin 4 (IL-4) is an anti-inflammatory cytokine related to
      different aspects of central nervous system development such as survival,
      proliferation, and differentiation, among others. Our goals were to investigate
      the effect of intravitreous treatment with IL-4 on the activation of downstream
      signaling pathways in the retina and the distribution of retinal axons within the
      superior colliculus (SC). MATERIAL AND METHODS: Lister hooded rats were submitted
      to an intravitreous injection of either IL-4 (5 U/uL) or PBS (vehicle) at
      postnatal day 10 (PND10). At PND11 or PND14, retinas were processed for Western
      blot or immunohistochemistry. At PND13, a group of animals received an
      intraocular injection of an anterograde tracer in the left (untreated) eye in
      order to label the uncrossed retinotectal axons. RESULTS: Our data revealed that
      intravitreous treatment with IL-4 at PND10 leads to a decrease in GFAP content
      and a sustained increase in the phosphorylation of STAT6 and ERK levels in the
      retina. IL-4 also increases retinal axonal arbors within the SC, compared to
      control groups. CONCLUSIONS: These data suggest that a single in vivo treatment
      with IL-4 during the early stages of development modulates signaling pathways in
      the retina, resulting in altered binocular subcortical visual connectivity.

PMID- 30110699
TI  - Association of the Aquaporin 3 Gene Polymorphism (rs2231231) with Epstein-Barr
      Virus-Associated Cancers in China.
AB  - BACKGROUND/AIMS: Aquaporins are widely expressed in a variety of cancers and were
      found to play an important role in cell migration, angiogenesis, tumor formation,
      and tumor development. Thus, they have been proposed as a potential biomarker for
      some cancers. Accordingly, we analyzed the association between a single
      nucleotide polymorphism locus of aquaporin 3 (rs2231231) and Epstein-Barr virus
      (EBV)-associated nasopharyngeal carcinoma (EBVaNPC), lymphoma (EBVaL), and
      gastric carcinoma in China. METHODS: Sequenom MassARRAY technique and polymerase
      chain reaction sequencing were used to test the genotype of 393 cases of patients
      with cancer and 148 normal control (NC) samples. A chi2 test or correction for
      continuity or the likelihood ratio was used for statistical analysis, and two
      sided p values < 0.05 were considered a statistically significant difference.
      RESULTS: We found that the genotype distributions were significantly different
      between either the EBVaNPC group and the NC group or the EBVaL case group and the
      NC group. However, no statistical associations between rs2231231 and gastric
      carcinoma was observed in the current study. CONCLUSIONS: The AQP3 gene
      polymorphism is associated with a susceptibility to EBVaNPC and EBVaL, and the
      homozygous AA genotype is more frequently observed in individuals who develop
      EBVaNPC and EBVaL.

PMID- 30110700
TI  - Evaluation of First-Trimester Physiological Midgut Herniation Using Three
      Dimensional Ultrasound.
AB  - INTRODUCTION: The aim of this study was to investigate the development of midgut
      herniation in vivo using three-dimensional (3D) ultrasonographic volume and
      distance measurements and to create reference data for physiological midgut
      herniation in ongoing pregnancies in a tertiary hospital population. MATERIALS
      AND METHODS: The transvaginal 3D ultrasound volumes of 112 women, seen weekly
      during the first trimester of pregnancy, were obtained and subsequently analysed
      in a virtual reality environment. The width of the umbilical cord insertion, the
      maximum diameter of the umbilical cord, and the volume of midgut herniation were
      measured from 6 until 13 weeks gestational age (GA). RESULTS: All parameters had
      a positive relation with GA, crown-rump length, and abdominal circumference. In
      approximately 1 of 10 volumes no midgut herniation could be observed at 9 and 10
      weeks GA. In 5.0% of the fetuses the presence of midgut herniation could still be
      visualised at 12 weeks GA. CONCLUSION: Reference charts for several dimensions of
      physiological midgut herniation were created. In the future, our data might be
      used as a reference in the first trimester for comparison in case of a suspected
      pathological omphalocele.

PMID- 30110701
TI  - Epidermal Lamellar Granules.
AB  - In the mid-1950s and 1960s, transmission electron microscopes became widely
      available, leading to many studies of the ultrastructure of various tissues
      including the epidermis. Most of these studies involved tissue fixation with
      formaldehyde and postfixation with osmium tetroxide. A few studies employed
      freeze-fracture electron microscopy. One set of these studies identified a small
      organelle variously called lamellar granules (LGs), lamellar bodies, membrane
      coating granules, cementsomes, and Odland bodies. LGs are round to ovoid in
      shape, with a diameter of about 200 nm. They have a bounding membrane surrounding
      a stack of internal lipid lamellae. These small organelles are first seen in the
      spinous layer and accumulate with differentiation in the granular layer. In the
      uppermost granular cells, the bounding membrane of the LG fuses into the cell
      plasma membrane, and the internal contents are extruded into the intercellular
      space. The initially extruded contents of the LG then rearrange to form the
      intercellular lamellae of the stratum corneum. In this context, LGs serve as the
      precursor to the permeability barrier of the skin. Various studies have provided
      evidence that they are derived from the Golgi apparatus, specifically the trans
      Golgi. Isolated LGs contain phosphoglycerides, sphingomyelin, and
      glucosylceramides. The most unusual lipid component is a linoleate-containing
      glucosylceramide comprising 30- to 34-carbon omega-hydroxy-acids. Isolated
      granules also contain acid hydrolases including glucocerebrosidase,
      sphingomyelinase, and phospholipase A. They also contain proteases and
      antimicrobial peptides. Defective LGs have been associated with a number of skin
      diseases including ichthyotic conditions and defective barrier function.
      Recently, studies employing cryo-transmission electron microscopy have called
      into question the validity of observations on LGs with more conventional electron
      microscopic techniques. These studies suggest a continuity of the membrane
      structure from the Golgi through the intercellular lamellae of the stratum
      corneum.

PMID- 30110703
TI  - Nanoparticle-Mediated Upconversion of Near-Infrared Light: A Step Closer to
      Optogenetic Neuromodulation in Humans.

PMID- 30110704
TI  - Fetal Goitrous Hypothyroidism and Polyhydramnios in a Patient with Compound
      Heterozygous DUOXA2 Mutations.
AB  - BACKGROUND: Fetal goiter is only rarely observed in pregnant women without
      autoimmune thyroid disorders, and there is no epidemiological data on its
      pathophysiology. Dual oxidase maturation factor 2 (DUOXA2), together with dual
      oxidase 2, serves pivotal roles in thyroid hormone biosynthesis. To date, all
      reported patients with DUOXA2 mutations were diagnosed postnatally through
      newborn screening for congenital hypothyroidism. CASE REPORT: The mother of a
      male fetus presented at 33 + 4 gestational weeks (GW) with a fetal goiter and
      polyhydramnios. Cordocentesis revealed fetal hypothyroidism (TSH 253.4 mU/L, FT4
      0.29 ng/dL). Intra-amniotic levothyroxine injections were performed at GW 34 + 3
      and 35 + 3. The patient was born after spontaneous vaginal delivery at 35 + 6 GW
      without obstetrical complications. He was treated with levothyroxine until the
      age of 6 years when reevaluation of his thyroid functions showed normal results
      (TSH 1.32 mU/L, FT4 1.81 ng/dL). Eleven causative genes of CH, including DUOXA2,
      were analyzed with use of a next-generation sequencing technique. RESULTS: A next
      generation sequencing-based mutation screen led us to find that he was compound
      heterozygous for 2 previously reported nonsense DUOXA2 mutations
      (p.[Tyr138*];[Tyr246*]). CONCLUSION: The present case not only illustrates the
      phenotypic diversity of DUOXA2 mutation carriers but also implies that DUOXA2 is
      important in prenatal thyroid hormone production.

PMID- 30110702
TI  - Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast
      Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in
      Vitro.
AB  - BACKGROUND/AIMS: Psoralen and bakuchiol are the main active compounds found in
      the traditional Chinese medicine Psoralea corylifolia L., and have been used to
      treat osteoporosis. This study aims to investigate the anti-osteoporosis effects
      of these two compounds using osteoclasts precursor differentiation and bone
      absorption assays in vitro. METHODS: Primary mouse osteoclasts precursor cells
      were induced by M-CSF (macrophage colony stimulating factor) plus RANKL (receptor
      activator of nuclear factor kappa-B ligand) in vitro. TRACP (tartrate-resistant
      acid phosphatase) enzyme activity and toluidine blue staining were used to
      observe the effects of psoralen and bakuchiol on osteoclast differentiation and
      bone resorption, respectively. Gelatin zymography was used to assess MMP (matrix
      metalloproteinase) activity, and ELISA was performed to measure cathepsin K
      activity. Western blotting analysis for expression of phosphorylated AKT, ERK, NF
      kB, and c-jun; and immunofluorescence analysis for c-jun and p65 nuclear
      translocation in induced osteoclasts were then used to determine the mechanism of
      anti-bone resorption of psoralen and bakuchiol. RESULTS: Mature osteoclasts were
      induced by M-CSF plus RANKL from primary bone marrow macrophages in vitro. Both
      psoralen and bakuchiol significantly inhibited TRACP enzyme activity and slightly
      decreased the number of TRACP+ multinuclear osteoclasts induced by M-CSF plus
      RANKL. Bakuchiol significantly decreased bone lacunae area and attenuated MMP-2
      activity induced by M-CSF plus RANKL in osteoclasts. Both psoralen and bakuchiol
      significantly decreased the expression and nuclear translocation of
      phosphorylated c-jun stimulated by M-CSF plus RANKL, but no significant effect on
      p65 translocation was observed in osteoclasts. Additionally, bakuchiol
      significantly attenuated the increased of M-CSF plus RANKL-induced
      phosphorylation of AKT in osteoclasts. CONCLUSIONS: Psoralen and bakuchiol
      ameliorated M-CSF plus RANKL-induced osteoclast differentiation and bone
      resorption via inhibition of AKT and AP-1 pathways activation in vitro.

PMID- 30110705
TI  - The Progression of the Stargardt Disease Type 4 (ProgStar-4) Study: Design and
      Baseline Characteristics (ProgStar-4 Report No. 1).
AB  - BACKGROUND/AIMS: To describe the design and baseline characteristics of patients
      enrolled in the multicenter, prospective natural history study of Stargardt
      disease type 4. METHODS: Fifteen eligible patients aged 6 years and older at
      baseline, harboring disease-causing variants in the PROM1 gene, and with
      specified ocular lesions were enrolled. They were examined at baseline using a
      standard protocol, with 6 monthly follow-up visits for a 2-year period including
      best-corrected ETDRS visual acuity, spectral-domain optical coherence tomography,
      fundus autofluorescence (FAF), mesopic and scotopic microperimetry (MP). Areas of
      definitely decreased FAF (DDAF) and questionably decreased FAF were outlined and
      quantified on FAF images. RESULTS: Amongst the 15 patients (29 eyes) that were
      enrolled at 5 centers in the USA and Europe, 10 eyes (34.5%) had areas of DDAF
      with an average lesion area of 3.2 +/- 3.5 mm2 (range 0.36-10.39 mm2) at
      baseline. The mean retinal sensitivity of the posterior pole derived from mesopic
      MP was 8.8 +/- 5.8 dB. CONCLUSIONS: Data on disease progression in PROM1-related
      retinopathy from this study will contribute to the characterization of the
      natural history of disease and the exploration of the utility of several
      modalities to track progression and therefore to potentially be used in future
      interventional clinical trials.

PMID- 30110706
TI  - Effect of Growth Hormone Therapy on Height Velocity in Korean Children with
      Idiopathic Short Stature: A Phase III Randomised Controlled Trial.
AB  - BACKGROUND/AIMS: The SYNERGY (Saizen(r) for Your New Life and Brighter Tomorrow
      without Growth Deficiency) study is the first randomised multi-centre, open-label
      study to assess the short-term efficacy and safety of this recombinant human
      growth hormone (r-hGH) preparation for prepubertal children with idiopathic short
      stature in South Korea. METHODS: The SYNERGY study (ClinicalTrials.gov
      NCT01746862) was conducted at 9 centres throughout South Korea between December
      2012 and March 2015. The primary endpoint was difference in height velocity from
      baseline to 6 months in the treatment and control arms. RESULTS: 97 children were
      screened; 90 were randomly assigned: 60 children to 0.067 mg/kg/day r-hGH for 12
      months (treatment) and 30 children to 6 months of no treatment followed by 0.067
      mg/kg/day r-hGH for 6 months (control). The 6-month mean height velocity in the
      treatment group increased from 5.63 cm/year (SD 1.62) to 10.08 cm/year (SD 1.92)
      (p < 0.0001) and from 4.94 cm/year (SD 1.91) to 5.92 cm/year (SD 2.01) (p =
      0.0938) in the control group (between-group difference 3.47 cm/year, 95% CI 2.17
      4.78; p < 0.0001). Adherence was > 90% throughout the study. The safety profile
      was consistent with that already known for r-hGH. CONCLUSION: Treatment with r
      hGH in the SYNERGY study demonstrated a statistically significant increase in
      height velocity at 6 months.

PMID- 30110707
TI  - Prepubertal Children Exposed to Maternal Gestational Diabetes Have Latent Low
      Grade Inflammation.
AB  - BACKGROUND: Maternal gestational diabetes mellitus (GDM) and overweight are
      associated with an increased risk of obesity and the metabolic syndrome in the
      adult offspring. We studied the influence of maternal GDM on prepubertal
      children's height, weight, body mass index (BMI), lipid and glucose metabolism,
      and low-grade inflammation. METHODS: A cohort of 135 prepubertal Caucasian
      children (age range 4.4-9.7 years) was studied in a controlled cross-sectional
      study. Seventy-seven children had been exposed to maternal GDM, and 58 children
      born after a normal pregnancy served as controls. The outcomes were height,
      weight, BMI, blood pressure, and biochemical markers of glucose and lipid
      metabolism and inflammation. RESULTS: There were no differences in height,
      weight, BMI, fasting serum insulin, plasma glucose, lipids, or blood pressure
      between the study groups. However, high-sensitivity C-reactive protein (hs-CRP)
      was significantly higher in the GDM group than in the controls (p = 0.001).
      CONCLUSIONS: Higher hs-CRP as a marker of low-grade inflammation was detected in
      prepubertal children exposed to maternal GDM, but no differences were seen in
      height, weight, BMI, or markers of glucose and lipid metabolism compared to
      control children. This finding may reflect an ongoing process of metabolic
      changes in children born after a GDM pregnancy.

PMID- 30110713
TI  - Neuronal histamine and the memory of emotionally salient events.
AB  - In this review, we describe the experimental paradigms used in preclinical
      studies to unravel the histaminergic brain circuits that modulate the formation
      and retrieval of memories associated with aversive events. Emotionally arousing
      events, especially bad ones, are remembered more accurately, clearly and for
      longer periods of time than neutral ones. Maladaptive elaborations of these
      memories may eventually constitute the basis of psychiatric disorders such as
      generalized anxiety, obsessive-compulsive disorders and post-traumatic stress
      disorder. A better understanding of the role of the histaminergic system in
      learning and memory has not only a theoretical significance but also a
      translational value. Ligands of histamine receptors are among the most used drugs
      worldwide; hence, understanding the impact of these compounds on learning and
      memory may help improve their pharmacological profile and unravel unexplored
      therapeutic applications.

PMID- 30110712
TI  - Dabigatran in ibrutinib-treated patients with atrial fibrillation and
      lymphoproliferative diseases: Experience of 4 cases.

PMID- 30110714
TI  - Association between household poverty dynamics and childhood overweight risk and
      health behaviours in the United States: a 8-year nationally representative
      longitudinal study of 16 800 children.
AB  - BACKGROUND: No study has examined how the pattern of income dynamics influences
      both of children's body mass index (BMI) trajectory and health behaviours.
      OBJECTIVES: To examine the association between household poverty dynamics and
      childhood overweight risk in the USA. METHODS: Using the longitudinal data of 16
      800 children (from kindergarten to the 8th grade) in the nationally
      representative US cohort-Early Childhood Longitudinal Study, Kindergarten Class
      1998-1999, we examined the differences in BMI trajectory, weight-related health
      behaviours and risk of overweight in association with household poverty dynamics
      during follow-up (never [no experience of poverty], transient [once], recurrent
      [>=2 times] and persistent poor [remained]) using mixed models with fractional
      polynomial functions and estimating equation models. RESULTS: Overall, children
      experiencing poverty were more likely to have adverse BMI growth trajectory and
      eating and sedentary behaviours compared with the never poor. The recurrently
      poor children (12.8%) had the fastest BMI trajectory, highest overweight/obesity
      prevalence from 5 to 16 years old and highest proportion of excessive soda/fast
      food consumption and irregular exercise at 8th grade than did others (p < 0.05).
      The persistently poor (8.4%) were the lowest in BMI growth trajectory but became
      the second highest in childhood obesity through a steady increase in BMI over
      time. Children in the recurrently poor group had a 1.5 times (95% CI = 1.0-2.2)
      higher risk of overweight than those having never experienced poverty during
      follow-up. CONCLUSIONS: The experience of recurrent household poverty had a
      significant association with children's adverse eating behaviours and increased
      obesity risk subsequently.

PMID- 30110715
TI  - Cortisol reactivity and weight gain among adolescents who vary in prenatal drug
      exposure.
AB  - OBJECTIVE: Low inhibitory control is linked with weight gain among youth.
      Inhibitory problems are associated with disruption to the hypothalamic-pituitary
      adrenal axis cortisol response. Increased cortisol predicts appetite and weight
      gain (though may be gender specific). This study hypothesized that cortisol
      reactivity explains the association between inhibition and weight gain while
      considering the moderating factors of early stressors to the hypothalamic
      pituitary-adrenal axis (e.g. prenatal-drug exposure) and gender. METHODS:
      Adolescents with prenatal-drug exposure (n = 76) and non-exposed comparison
      adolescents (NE; n = 61) completed the Conner's Continuous Performance Test and
      provided salivary cortisol samples. BMI z-score were measured at the initial and
      12-month follow-up evaluations. A bootstrapped moderated mediation analysis was
      conducted to test for conditional indirect effects of cortisol reactivity.
      RESULTS: Lower inhibition was associated with increased cortisol reactivity among
      youth who were NE, and increased cortisol reactivity was associated with weight
      gain among girls. Cortisol reactivity mediated the relation between inhibition
      and BMI z-score change for the girls in the group who was NE. CONCLUSION:
      Increased cortisol reactivity may play a mechanistic role in predicting weight
      gain among non-prenatally drug-exposed girls. Cortisol reactivity may be a
      biomarker for targeted interventions to improve biological regulation and
      ultimately health risk among girls.

PMID- 30110711
TI  - Evaluation of the adequacy of drug prescriptions in patients with chronic kidney
      disease: results from the CKD-REIN cohort.
AB  - AIMS: Drug prescription is difficult to manage in patients with chronic kidney
      disease (CKD). We assessed the prevalence and determinants of inappropriate drug
      prescriptions (whether contraindications or inappropriately high doses) with
      regard to kidney function in patients with CKD under nephrology care. We also
      assessed the impact of the equation used to estimate GFR on the prevalence
      estimates. METHODS: The CKD-REIN cohort includes 3033 outpatients with CKD (eGFR
      between 15 and 60 ml min-1  1.73 m-2 ). We examined the daily doses of
      pharmacological agents prescribed at study entry. Inappropriate prescription was
      defined as the reported prescription of either a contraindicated drug or an
      indicated drug at an inappropriately high dose level with regard to the patient's
      GFR, as estimated with the CKD-EPI equation, the de-indexed CKD-EPI equation, or
      the Cockcroft-Gault (CG) equation. Multivariate logistic regression was used to
      assess the determinants of inappropriate prescription risk. RESULTS: At baseline,
      patients' median [interquartile range] number of drugs prescribed per patient was
      8 [5-10]. Half of the patients had been prescribed at least one inappropriate
      drug. Anti-gout, cardiovascular agents and antidiabetic agents accounted for most
      of the inappropriate prescriptions. The percentage of inappropriate prescriptions
      varied from one GFR equation to another: 52% when using the CKD-EPI equation, 47%
      when using the de-indexed CKD-EPI equation and 41% with the CG equation. A
      multiple logistic regression analysis showed significantly higher odds ratios
      [95% confidence interval] for inappropriate prescriptions in male patients (1.28
      [1.07; 1.53]), patients with diabetes (1.34 [1.06; 1.70]), those with a high BMI
      (1.58 [1.25; 1.99]), and those with a low GFR (10.2 [6.02; 17.3]). The risk of
      having at least one inappropriate prescription increased with the number of drugs
      per patient (P for trend < 0.0001) and therefore the odds ratio was 5.88 [4.17;
      8.28] for those who received at least 11 prescribed medications compared to those
      who received fewer than 5. CONCLUSION: Our results emphasize the complexity of
      drug management for CKD patients, for whom inappropriate prescription appears to
      be common.

PMID- 30110716
TI  - Social exclusion of the adolescent with overweight: study of sociocentric social
      networks in the classroom.
AB  - BACKGROUND: Multiple studies have shown the social consequences of suffering
      overweight, with social exclusion or isolation as some of the most important. In
      order to study the social patterns among adolescents, we have set as objectives
      to analyse the position of the individual within their network from a
      sociocentric perspective, comparing the relational pattern of the adolescents
      suffering from overweight with those who are normal weight. METHOD: This was a
      cross-sectional descriptive study using logistic regression and social network
      analysis. We analysed the contact patterns of 235 adolescents in 11 social
      networks, classifying contact into three levels of intensity: minimum,
      intermediate and maximum (friendship). The WHO reference was used for the
      variable of overweight. RESULTS: The prevalence of overweight was 30.2% (25.5%
      overweight and 4.7% obesity). An analysis of the relational patterns of
      individuals with overweight showed that at the minimum contact level, they
      established fewer relationships and less closeness (odds ratio [OR]: 2.32;
      confidence interval [CI] 95%: 1.17-4.66; p-value: 0.016). This effect was more
      marked in female adolescents. At intermediate contact level, they had few
      relationships and low prestige (OR: 3.29; CI: 95%; 1.03-10.51; p-value: 0.045,
      OR: 3.18; CI: 95%; 1.00-10.04; p-value: 0.049, respectively). At maximum contact
      level (friendship), female adolescents related little with other adolescents (OR:
      3.78; CI: 95%; 1.07-13.32; p-value: 0.038). CONCLUSIONS: Adolescents with
      overweight take up peripheral positions within their social network, choosing by
      themselves not to establish contact with others. Social network analysis is
      crucial to detect adolescents with overweight at risk of exclusion and help
      alleviate psychological and social deficits.

PMID- 30110717
TI  - Dose-intensified bendamustine and melphalan (BenMel) conditioning before second
      autologous transplantation in myeloma patients.
AB  - Consolidation in myeloma patients with high-dose melphalan chemotherapy (Mel
      HDCT) and autologous transplantation (ASCT) is standard of care since more than 2
      decades. However, definite cure remains exceptional despite intensive treatment,
      and improving effectiveness of HDCT remains an unmet clinical need. Combining
      intensified bendamustine with melphalan may represent an option. We analyzed
      safety and efficacy of combining dose-intensified bendamustine (200 mg/m2 on days
      -4/-3) with high-dose melphalan (100 mg/m2 on days -2/-1) before a second
      (tandem) ASCT in adverse risk myeloma patients after Mel HDCT/ASCT1. Twelve
      patients received BenMel conditioning before ASCT2 because of high-risk
      cytogenetics and/or failure to achieve complete remission (CR) after Mel
      HDCT/ASCT1. Comparing Mel HDCT/ASCT1 and BenMel HDCT/ASCT2, we observed no
      differences in hematologic recovery and tolerance. Acute renal injury after
      BenMel conditioning occurred in 3 (25%) patients, but was reversible in all
      patients, and there were no treatment related deaths. Complete remission rates
      were increasing from 42% after Mel/ASCT1 to 75% after BenMel/ASCT2. PFS 1 year
      after ASCT2 was 67%, and OS was 83%. These data suggest that dose-intensified
      bendamustine with melphalan conditioning is safe and warrants a prospective
      randomized comparison to standard melphalan HDCT in myeloma patients.

PMID- 30110718
TI  - E-Health interventions for anxiety and depression in children and adolescents
      with long-term physical conditions.
AB  - BACKGROUND: Long-term physical conditions affect 10% to 12% of children and
      adolescents worldwide; these individuals are at greater risk of developing
      psychological problems, particularly anxiety and depression. Access to face-to
      face treatment for such problems is often limited, and available interventions
      usually have not been tested with this population. As technology improves, e
      health interventions (delivered via digital means, such as computers and smart
      phones and ranging from simple text-based programmes through to multimedia and
      interactive programmes, serious games, virtual reality and biofeedback
      programmes) offer a potential solution to address the psychological needs of this
      group of young people. OBJECTIVES: To assess the effectiveness of e-health
      interventions in comparison with attention placebos, psychological placebos,
      treatment as usual, waiting-list controls, or non-psychological treatments for
      treating anxiety and depression in children and adolescents with long-term
      physical conditions. SEARCH METHODS: We searched the Cochrane Common Mental
      Disorders Group's Controlled Trials Register (CCMDTR to May 2016), the Cochrane
      Central Register of Controlled Trials (CENTRAL) (Issue 8, 2017), Web of Science
      (1900 - 18 August 2016, updated 31 August 2017) and Ovid MEDLINE, Embase,
      PsycINFO (cross-search 2016 to 18 Aug 2017). We hand-searched relevant conference
      proceedings, reference lists of included articles, and the grey literature to May
      2016. We also searched international trial registries to identify unpublished or
      ongoing trials. SELECTION CRITERIA: We included randomised controlled trials
      (RCTs), cluster-randomised trials, and cross-over trials of e-health
      interventions for treating any type of long-term physical condition in children
      and adolescents (aged 0 to 18 years), and that measured changes in symptoms or
      diagnoses of anxiety, depression, or subthreshold depression. We defined long
      term physical conditions as those that were more than three-months' duration. We
      assessed symptoms of anxiety and depression using patient- or clinician
      administered validated rating scales based on DSM III, IV or 5 (American
      Psychological Association 2013), or ICD 9 or 10 criteria (World Health
      Organization 1992). Formal depressive and anxiety disorders were diagnosed using
      structured clinical interviews. Attention placebo, treatment as usual, waiting
      list, psychological placebo, and other non-psychological therapies were eligible
      comparators. DATA COLLECTION AND ANALYSIS: Two review authors independently
      reviewed titles, abstracts, and full-text articles; discrepancies were resolved
      through discussion or addressed by a third author. When available, we used odds
      ratio (OR) to compare dichotomous data and standardised mean differences (SMD) to
      analyse continuous data, both with 95% confidence intervals (CI). We undertook
      meta-analysis when treatments, participants, and the underlying clinical question
      were adequately similar. Otherwise, we undertook a narrative analysis. MAIN
      RESULTS: We included five trials of three interventions (Breathe Easier Online,
      Web-MAP, and multimodal cognitive behavioural therapy (CBT)), which included 463
      participants aged 10 to 18 years. Each trial contributed to at least one meta
      analysis. Trials involved children and adolescents with long-term physical
      conditions, such as chronic headache (migraine, tension headache, and others),
      chronic pain conditions (abdominal, musculoskeletal, and others), chronic
      respiratory illness (asthma, cystic fibrosis, and others), and symptoms of
      anxiety or depression. Participants were recruited from community settings and
      hospital clinics in high income countries.For the primary outcome of change in
      depression symptoms versus any control, there was very low-quality evidence
      meaning that it could not be determined whether e-health interventions were
      clearly better than any comparator (SMD -0.06, 95% CI -0.35 to 0.23; five RCTs,
      441 participants). For the primary outcome of change in anxiety symptoms versus
      any comparator, there was very low-quality evidence meaning that it could not be
      determined whether e-health interventions were clearly better than any comparator
      (SMD -0.07, 95% CI -0.29 to 0.14; two RCTs, 324 participants). For the primary
      outcome of treatment acceptability, there was very low-quality evidence that e
      health interventions were less acceptable than any comparator (SMD 0.46, 95% CI
      0.23 to 0.69; two RCTs, 304 participants).For the secondary outcome of quality of
      life, there was very low-quality evidence meaning that it could not be determined
      whether e-health interventions were clearly better than any comparator (SMD 
      0.83, 95% CI -1.53 to -0.12; one RCT, 34 participants). For the secondary outcome
      of functioning, there was very low-quality evidence meaning that it could not be
      determined whether e-health interventions were clearly better than any comparator
      (SMD -0.08, 95% CI -0.33 to 0.18; three RCTs, 368 participants). For the
      secondary outcome of status of long-term physical condition, there was very low
      quality evidence meaning that it could not be determined whether e-health
      interventions were clearly better than any comparator (SMD 0.06, 95% CI -0.12 to
      0.24; five RCTs, 463 participants).The risk of selection bias was considered low
      in most trials. However, the risk of bias due to inadequate blinding of
      participants or outcome assessors was considered unclear or high in all trials.
      Only one study had a published protocol; two trials had incomplete outcome data.
      All trials were conducted by the intervention developers, introducing another
      possible bias. No adverse effects were reported by any authors. AUTHORS'
      CONCLUSIONS: At present, the field of e-health interventions for the treatment of
      anxiety or depression in children and adolescents with long-term physical
      conditions is limited to five low quality trials. The very low-quality of the
      evidence means the effects of e-health interventions are uncertain at this time,
      especially in children aged under 10 years.Although it is too early to recommend
      e-health interventions for this clinical population, given their growing number,
      and the global improvement in access to technology, there appears to be room for
      the development and evaluation of acceptable and effective technologically-based
      treatments to suit children and adolescents with long-term physical conditions.

PMID- 30110719
TI  - Erythropoietic effects of low-dose cobalt application.
AB  - Cobaltous ions (Co2+ ) stabilize HIFalpha, increase endogenous erythropoietin
      (EPO) production, and may, therefore, be used as a performance-enhancing
      substance. To date, the dosage necessary to stimulate erythropoiesis is unknown.
      The aim of this study was, therefore, to determine the minimum dosage necessary
      to increase erythropoietic processes. In a first double-blind placebo-controlled
      study (n = 5), single oral Co2+ dosages of 5 mg (n = 6) and 10 mg (n = 7) were
      administered to healthy young men. Cubital venous blood and urine samples were
      collected before and up to 24 hours after Co2+ administration. In a second study,
      the same daily Co2+ dosages were administered for five days (placebo: n = 5, 5
      mg: n = 9, 10 mg: n = 7). Blood and urine samples were taken the day before
      administration and at day 3 and day 5. Plasma [EPO] was elevated by 20.5 +/-
      16.9% at 5 hours after the single 5-mg administration (p < 0.05) and by 52.8 +/-
      23.5% up to 7 hours following the 10-mg Co2+ administration (p < 0.001). Urine
      [Co2+ ] transiently increased, with maximum values 3-5 hours after Co2+ ingestion
      (5 mg: from 0.8 +/- 1.1 to 153.6 +/- 109.4 ng/mL, 10 mg: from 1.3 +/- 1.7 to
      338.0 +/- 231,5 ng/mL). During the five days of Co2+ application, 5 mg showed a
      strong tendency to increase [EPO], while the 10-mg application significantly
      increased [EPO] at day 5 by 27.2 +/- 26.4% (p < 0.05) and the immature
      reticulocyte fraction by 49.9 +/- 21.7% (p < 0.01). [Ferritin] was decreased by
      12.4 +/- 10.4 ng/mL (p < 0.05). An oral Co2+ dosage of 10 mg/day exerts clear
      erythropoietic effects, and 5 mg/day tended to increase plasma EPO concentration.

PMID- 30110721
TI  - Enhancing network synchronization by phase modulation.
AB  - Due to time delays in signal transmission and processing, phase lags are
      inevitable in realistic complex oscillator networks. Conventional wisdom is that
      phase lags are detrimental to network synchronization. Here we show that
      judiciously chosen phase lag modulations can result in significantly enhanced
      network synchronization. We justify our strategy of phase modulation, demonstrate
      its power in facilitating and enhancing network synchronization with synthetic
      and empirical network models, and provide an analytic understanding of the
      underlying mechanism. Our work provides an alternative approach to
      synchronization optimization in complex networks, with insights into control of
      complex nonlinear networks.

PMID- 30110720
TI  - Unleashing the Therapeutic Potential of CAR-T Cell Therapy Using Gene-Editing
      Technologies.
AB  - Chimeric antigen receptor (CAR) T-cell therapy, an emerging immunotherapy, has
      demonstrated promising clinical results in hematological malignancies including B
      cell malignancies. However, accessibility to this transformative medicine is
      highly limited due to the complex process of manufacturing, limited options for
      target antigens, and insufficient anti-tumor responses against solid tumors.
      Advances in gene-editing technologies, such as the development of Zinc Finger
      Nucleases (ZFNs), Transcription Activator-Like Effector Nucleases (TALENs), and
      Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR/Cas9), have
      provided novel engineering strategies to address these limitations. Development
      of next-generation CAR-T cells using gene-editing technologies would enhance the
      therapeutic potential of CAR-T cell treatment for both hematologic and solid
      tumors. Here we summarize the unmet medical needs of current CAR-T cell therapies
      and gene-editing strategies to resolve these challenges as well as safety
      concerns of gene-edited CAR-T therapies.

PMID- 30110722
TI  - XXZ-Ising model on the triangular kagome lattice with spin 1 on the decorated
      trimers.
AB  - We consider the triangular kagome XXZ-Ising model (TKL XXZ-Ising model) formed by
      inserting small triangles ("a-trimers") with XXZ spin-1 inside the triangles of
      the kagome lattice ("b-trimers"). It is a mixed spin system and can be solved
      exactly by transforming into the kagome lattice with the general transformation
      method for decorated spin systems. In the absence of an external field, we
      integrate out the quantum spins of the a-trimers and map the TKL model to the
      kagome Ising model exactly. We obtain the full phase diagram and their zero
      temperature entropies (e.g., s_{max}=5.48895 per unit cell is given for the phase
      with the maximum entropy). When an external field is applied, 20 phases are found
      due to the quantum fluctuations of a-trimers. Moreover, the high spins in the a
      trimers can lead to a stable quantized growth of the magnetization process in the
      Heisenberg limit.

PMID- 30110723
TI  - Simulation of knock probability in an internal combustion engine.
AB  - In spark-ignition internal combustion engines, fluctuations of the in-cylinder
      pressure trace and the tendency of combustion knock are usually different from
      one cycle to another. These cycle-to-cycle variations are affected by the initial
      state at ignition time and the subsequent burning. The occurrence of the
      phenomena is unpredictable, and their stochastic nature offers challenges in the
      optimization of engine control strategies. In this paper, a simulator providing a
      series of cycle-to-cycle varied in-cylinder pressures is introduced. The Wiebe
      function and Livengood-Wu integration are used to describe the determinacy of
      combustion. Various means, including the Markov chain, are introduced to express
      the stochastic quantities during combustion. In addition, the combustion of a
      given knock probability is simulated.

PMID- 30110724
TI  - Controlling wetting with electrolytic solutions: Phase-field simulations of a
      droplet-conductor system.
AB  - The wetting properties of immiscible two-phase systems are crucial in
      applications ranging from laboratory-on-a-chip devices to field-scale oil
      recovery. It has long been known that effective wetting properties can be altered
      by the application of an electric field; a phenomenon coined as electrowetting.
      Here, we consider theoretically and numerically a single droplet sitting on an
      (insulated) conductor, i.e., within a capacitor. The droplet consists of a pure
      phase without solutes, while the surrounding fluid contains a symmetric
      monovalent electrolyte, and the interface between them is impermeable. Using
      nonlinear Poisson-Boltzmann theory, we present a theoretical prediction of the
      dependency of the apparent contact angle on the applied electric potential. We
      then present well-resolved dynamic simulations of electrowetting using a phase
      field model, where the entire two-phase electrokinetic problem, including the
      electric double layers (EDLs), is resolved. The simulations show that, while the
      contact angle on scales smaller than the EDL is unaffected by the application of
      an electric field, an apparent contact angle forms on scales beyond the EDL. This
      contact angle relaxes in time towards a saturated apparent contact angle. The
      dependency of the contact angle upon applied electric potential is in good
      agreement with the theoretical prediction. The only phenomenological parameter in
      the prediction is shown to depend on the permeability ratio between the two
      phases. Based on the resulting unified description, we obtain an effective
      expression of the contact angle which can be used in more macroscopic numerical
      simulations, i.e. where the electrokinetic problem is not fully resolved.

PMID- 30110725
TI  - Route to bursting via pulse-shaped explosion.
AB  - This Rapid Communication reports on the discovery of a route to bursting, called
      a pulse-shaped explosion (PSE), for a paradigmatic class of nonlinear
      oscillators. We find that both an equilibrium and a limit cycle can exhibit pulse
      shaped sharp quantitative changes in relation to the variation of system
      parameters, which are interesting explosive behaviors, the PSE. It leads to large
      amplitude oscillations in the rest phase (i.e., small-amplitude oscillations) of
      bursting, giving rise to additional active phases alternating with the rest
      phase, and finally determines compound bursting structures. This way, the route
      to complex bursting dynamics by PSE is explained and its robustness is shown. PSE
      opens different ways for the control dynamics of complex systems.

PMID- 30110726
TI  - Chaotic Rayleigh-Benard convection with finite sidewalls.
AB  - We explore the role of finite sidewalls on chaotic Rayleigh-Benard convection. We
      use large-scale parallel spectral-element numerical simulations for the precise
      conditions of experiment for cylindrical convection domains. We solve the
      Boussinesq equations for thermal convection and the conjugate heat transfer
      problem for the energy transfer at the solid sidewalls of the cylindrical domain.
      The solid sidewall of the convection domain has finite values of thickness,
      thermal conductivity, and thermal diffusivity. We compute the Lyapunov vectors
      and exponents for the entire fluid-solid coupled problem. We quantify the chaotic
      dynamics of convection over a range of thermal sidewall boundary conditions. We
      find that the dynamics become less chaotic as the thermal conductivity of the
      sidewalls increases as measured by the value of the fractal dimension of the
      dynamics. The thermal conductivity of the sidewall is a stabilizing influence;
      the heat transfer between the fluid and solid regions is always in the direction
      to reduce the fluid motion near the sidewalls. Although the heat interaction for
      strongly conducting sidewalls is only about 1% of the heat transfer through the
      fluid layer, it is sufficient to reduce the fractal dimension of the dynamics by
      approximately 25% in our computations.

PMID- 30110727
TI  - Structure of sticky-hard-sphere random aggregates: The viewpoint of contact
      coordination and tetrahedra.
AB  - We study more than 10^{4} random aggregates of 10^{6} monodisperse sticky hard
      spheres each, generated by various static algorithms. Their packing fraction
      varies from 0.370 up to 0.593. These aggregates are shown to be based on two
      types of disordered structures: random regular polytetrahedra and random
      aggregates, the former giving rise to delta peaks on pair distribution functions.
      Distortion of structural (Delaunay) tetrahedra is studied by two parameters,
      which show some similarities and some differences in terms of overall tendencies.
      Isotropy of aggregates is characterized by the nematic order parameter. The
      overall structure is then studied by distinguishing spheres in function of their
      contact coordination number (CCN). Distributions of average CCN around spheres of
      a given CCN value show trends that depend on packing fraction and building
      algorithms. The radial dependence of the average CCN turns out to be dependent
      upon the CCN of the central sphere and shows discontinuities that resemble those
      of the pair distribution function. Moreover, it is shown that structural details
      appear when the CCN is used as pseudochemical parameter, such as various angular
      distribution of bond angles, partial pair distribution functions, Ashcroft
      Langreth and Bhatia-Thornton partial structure factors. These allow
      distinguishing aggregates with the same values of packing fraction or average
      tetrahedral distortion or even similar global pair distribution function,
      indicative of the great interest of paying attention to contact coordination
      numbers to study more precisely the structure of random aggregates.

PMID- 30110728
TI  - Resonance-induced energy localization in a weakly dissipative nonlinear chain.
AB  - This work investigates the emergence of resonance and resonance-induced
      localization in a weakly dissipative chain of coupled anharmonic oscillators
      under the influence of a harmonic force applied at one end of the chain. The
      dynamics of the chain is studied assuming 1:1 (fundamental) resonance, when the
      response of each nonlinear oscillator has a dominant harmonic component with the
      frequency close to the frequency of the external excitation. It is shown that
      weak dissipation in a strongly nonlinear chain may be a key factor preventing
      large-amplitude resonance. The resulting process in the dissipative system
      represents resonance-induced large-amplitude oscillations of a part of the chain
      adjacent to the actuator and escape from resonance of the distant oscillators.
      Conditions of the emergence of resonance and energy localization are derived. The
      obtained solutions indicate that the maximal concentration of energy on the
      excited oscillator arises together with equipartition of energy among the other
      resonant oscillators. An agreement between the analytical and numerical results
      is demonstrated.

PMID- 30110729
TI  - Generalized Langevin equation formulation for anomalous diffusion in the Ising
      model at the critical temperature.
AB  - We consider the two- (2D) and three-dimensional (3D) Ising models on a square
      lattice at the critical temperature T_{c}, under Monte Carlo spin flip dynamics.
      The bulk magnetization and the magnetization of a tagged line in the 2D Ising
      model, and the bulk magnetization and the magnetization of a tagged plane in the
      3D Ising model, exhibit anomalous diffusion. Specifically, their mean-square
      displacements increase as power laws in time, collectively denoted as ~t^{c},
      where c is the anomalous exponent. We argue that the anomalous diffusion in all
      these quantities for the Ising model stems from time-dependent restoring forces,
      decaying as power laws in time-also with exponent c -in striking similarity to
      anomalous diffusion in polymeric systems. Prompted by our previous work that has
      established a memory-kernel based generalized Langevin equation (GLE) formulation
      for polymeric systems, we show that a closely analogous GLE formulation holds for
      the Ising model as well. We obtain the memory kernels from spin-spin correlation
      functions, and the formulation allows us to consistently explain anomalous
      diffusion as well as anomalous response of the Ising model to an externally
      applied magnetic field in a consistent manner.

PMID- 30110730
TI  - Two golden times in two-step contagion models: A nonlinear map approach.
AB  - The two-step contagion model is a simple toy model for understanding pandemic
      outbreaks that occur in the real world. The model takes into account that a
      susceptible person either gets immediately infected or weakened when getting into
      contact with an infectious one. As the number of weakened people increases, they
      eventually can become infected in a short time period and a pandemic outbreak
      occurs. The time required to reach such a pandemic outbreak allows for
      intervention and is often called golden time. Understanding the size-dependence
      of the golden time is useful for controlling pandemic outbreak. Using an approach
      based on a nonlinear mapping, here we find that there exist two types of golden
      times in the two-step contagion model, which scale as O(N^{1/3}) and O(N^{zeta})
      with the system size N on Erdos-Renyi networks, where the measured zeta is
      slightly larger than 1/4. They are distinguished by the initial number of
      infected nodes, o(N) and O(N), respectively. While the exponent 1/3 of the N
      dependence of the golden time is universal even in other models showing
      discontinuous transitions induced by cascading dynamics, the measured zeta
      exponents are all close to 1/4 but show model-dependence. It remains open whether
      or not zeta reduces to 1/4 in the asymptotically large-N limit. Our method can be
      applied to several models showing a hybrid percolation transition and gives
      insight into the origin of the two golden times.

PMID- 30110731
TI  - Orchestrating cells on a chip: Employing surface acoustic waves towards the
      formation of neural networks.
AB  - For the investigation of cell-cell interaction in general and for neural
      communication and future applications of neural networks, a controllable and well
      defined network structure is crucial. We here propose the implementation of an
      acoustically driven system for tunable and deliberate stimulation and
      manipulation of cell growth on a chip. This piezoelectric chip allows us to
      generate a checkerboard-like standing surface acoustic wave pattern coupled to a
      fluid layer in a microfluidic chamber on top. Such a dynamically induced
      patterning lattice is shown to allow for the active positioning of the neurons
      and subsequent guided neurite outgrowth, thus finally overcoming the limitations
      of static approaches. After thorough characterization of the resulting tunable
      potential landscape, we successfully demonstrate cell adhesion and even growth of
      the such positioned cells within the well-defined pressure nodes. We demonstrate
      neuron growth at predetermined positions and observe a subsequent neurite
      outgrowth, even being correlated with the artificial potential landscape. For the
      very delicate and sensitive primary neural cells, this is a change of paradigm!
      Our experimental findings give us confidence that our hybrid lab-on-a-chip system
      in the near future will allow researchers to study cell-cell interaction of
      primary neurons. If scaled to a true network level, it will enable us to control
      and study how neural networks connect, interact, and communicate.

PMID- 30110732
TI  - Robustness and fragility of the susceptible-infected-susceptible epidemic models
      on complex networks.
AB  - We analyze two alterations of the standard susceptible-infected-susceptible (SIS)
      dynamics that preserve the central properties of spontaneous healing and
      infection capacity of a vertex increasing unlimitedly with its degree. All models
      have the same epidemic thresholds in mean-field theories but depending on the
      network properties, simulations yield a dual scenario, in which the epidemic
      thresholds of the modified SIS models can be either dramatically altered or
      remain unchanged in comparison with the standard dynamics. For uncorrelated
      synthetic networks having a power-law degree distribution with exponent
      gamma<5/2, the SIS dynamics are robust exhibiting essentially the same outcomes
      for all investigated models. A threshold in better agreement with the
      heterogeneous rather than quenched mean-field theory is observed in the modified
      dynamics for exponent gamma>5/2. Differences are more remarkable for gamma>3,
      where a finite threshold is found in the modified models in contrast with the
      vanishing threshold of the original one. This duality is elucidated in terms of
      epidemic lifespan on star graphs. We verify that the activation of the modified
      SIS models is triggered in the innermost component of the network given by a k
      core decomposition for gamma<3 while it happens only for gamma<5/2 in the
      standard model. For gamma>3, the activation in the modified dynamics is
      collective involving essentially the whole network while it is triggered by hubs
      in the standard SIS. The duality also appears in the finite-size scaling of the
      critical quantities where mean-field behaviors are observed for the modified but
      not for the original dynamics. Our results feed the discussions about the most
      proper conceptions of epidemic models to describe real systems and the choices of
      the most suitable theoretical approaches to deal with these models.

PMID- 30110733
TI  - Role of charge regulation and flow slip in the ionic conductance of nanopores: An
      analytical approach.
AB  - The number of precise conductance measurements in nanopores is quickly growing.
      To clarify the dominant mechanisms at play and facilitate the characterization of
      such systems for which there is still no clear consensus, we propose an
      analytical approach to the ionic conductance in nanopores that takes into account
      (i) electro-osmotic effects, (ii) flow slip at the pore surface for hydrophobic
      nanopores, (iii) a component of the surface charge density that is modulated by
      the reservoir pH and salt concentration c_{s} using a simple charge regulation
      model, and (iv) a fixed surface charge density that is unaffected by pH and
      c_{s}. Limiting cases are explored for various ranges of salt concentration and
      our formula is used to fit conductance experiments found in the literature for
      carbon nanotubes. This approach permits us to catalog the different possible
      transport regimes and propose an explanation for the wide variety of currently
      known experimental behavior for the conductance versus c_{s}.

PMID- 30110734
TI  - Lattice Boltzmann simulation of droplet dynamics on granular surfaces with
      variable wettability.
AB  - Soil-composing particles undergo wettability changes, impacting hydraulic and
      mechanical processes such as erosion and landslides. Such processes evolve at
      very small scales, typically at the particle level. Here we capture the evolution
      of liquid interfaces in a single particle and several particles with the lattice
      Boltzmann (LB) method. The paper presents a three-dimensional LB study on the
      droplet dynamics on a layer of uniformly packed spherical particles with varying
      size and intrinsic contact angle (CA) aimed at mimicking conditions comparable to
      those of real soils. The numerical droplet is initialized close to the granular
      surface and deposited by gravity. Three spreading and infiltration behaviors were
      identified: a droplet with a stable apparent CA, a droplet with a metastable
      apparent CA before infiltration, and immediate infiltration. The results showed
      that the formation of a droplet with a stable or metastable spherical-cap shape
      depends on the particle size and the intrinsic CA. Furthermore, the initial
      wetted zone expansion was found to be governed by inertial effects with its
      behavior characterized by a power law. Finally, the apparent CA, which is closely
      related to the intrinsic CA, was found to be influenced by the particle size due
      to a significant portion of the droplet being embedded into the granular surface
      for the larger particles and reducing the apparent CA. This paper provides a
      basis for future research targeting the behavior of droplet interaction with
      granular surfaces with variable intrinsic CAs (from wettable to superhydrophobic)
      such as soils and other granular materials for industrial applications. The
      numerical approach implemented can also be extended to model other dynamic
      processes for a droplet, such as evaporation, high-velocity impacting, and
      lateral sliding.

PMID- 30110735
TI  - Interplay between polydispersity, inelasticity, and roughness in the freely
      cooling regime of hard-disk granular gases.
AB  - A polydisperse granular gas made of inelastic and rough hard disks is considered.
      Focus is laid on the kinetic-theory derivation of the partial energy production
      rates and the total cooling rate as functions of the partial densities and
      temperatures (both translational and rotational) and of the parameters of the
      mixture (masses, diameters, moments of inertia, and mutual coefficients of normal
      and tangential restitution). The results are applied to the homogeneous cooling
      state of the system and the associated nonequipartition of energy among the
      different components and degrees of freedom. It is found that disks typically
      present a stronger rotational-translational nonequipartition but a weaker
      component-component nonequipartition than spheres. A noteworthy "mimicry" effect
      is unveiled, according to which a polydisperse gas of disks having common values
      of the coefficient of restitution and of the reduced moment of inertia can be
      made indistinguishable from a monodisperse gas in what concerns the degree of
      rotational-translational energy nonequipartition. This effect requires the mass
      of a disk of component i to be approximately proportional to 2sigma_{i}+<sigma>,
      where sigma_{i} is the diameter of the disk and <sigma> is the mean diameter.

PMID- 30110736
TI  - Autonomous stochastic resonance driven by colored noise.
AB  - A one-dimensional linear autonomous system coupled to a generic stationary
      nonequilibrium fluctuating bath can exhibit resonant response when its damped
      oscillation period matches some characteristic bath's relaxation time. This
      condition justifies invoking the stochastic resonance paradigm, even if it can be
      achieved more easily by tuning the system to the bath and not vice versa, as is
      usually the case. The simple nature of the mechanism numerically investigated
      here suggests a number of interesting applications for instance in the context of
      (1) energy harvesting from random ambient vibrations, (2) activated barrier
      crossing through a saddle point, or (3) an unstable limit cycle.

PMID- 30110737
TI  - Dispersion of particles in an infinite-horizon Lorentz gas.
AB  - We consider a two-dimensional Lorentz gas with infinite horizon. This
      paradigmatic model consists of pointlike particles undergoing elastic collisions
      with fixed scatterers arranged on a periodic lattice. It was rigorously shown
      that when t->infinity, the distribution of particles is Gaussian. However, the
      convergence to this limit is ultraslow, hence it is practically unattainable.
      Here, we obtain an analytical solution for the Lorentz gas' kinetics on
      physically relevant timescales, and find that the density in its far tails decays
      as a universal power law of exponent -3. We also show that the arrangement of
      scatterers is imprinted in the shape of the distribution.

PMID- 30110738
TI  - Critical exponents of the yielding transition of amorphous solids.
AB  - We investigate numerically the yielding transition of a two-dimensional model
      amorphous solid under external shear. We use a scalar model in terms of values of
      the total local strain, derived from the full (tensorial) description of the
      elastic interactions in the system, in which plastic deformations are accounted
      for by introducing a stochastic "plastic disorder" potential. This scalar model
      is seen to be equivalent to a collection of Prandtl-Tomlinson particles, which
      are coupled through an Eshelby quadrupolar kernel. Numerical simulations of this
      scalar model reveal that the strain rate versus stress curve, close to the
      critical stress, is of the form gamma[over ]~(sigma-sigma_{c})^{beta}.
      Remarkably, we find that the value of beta depends on details of the microscopic
      plastic potential used, confirming and giving additional support to results
      previously obtained with the full tensorial model. To rationalize this result, we
      argue that the Eshelby interaction in the scalar model can be treated to a good
      approximation in a sort of "dynamical" mean field, which corresponds to a Prandtl
      Tomlinson particle that is driven by the applied strain rate in the presence of a
      stochastic noise generated by all other particles. The dynamics of this Prandtl
      Tomlinson particle displays different values of the beta exponent depending on
      the analytical properties of the microscopic potential, thus giving support to
      the results of the numerical simulations. Moreover, we find that other critical
      exponents that depend on details of the dynamics show also a dependence with the
      form of the disorder, while static exponents are independent of the details of
      the disorder. Finally, we show how our scalar model relates to other
      elastoplastic models and to the widely used mean-field version known as the
      Hebraud-Lequeux model.

PMID- 30110739
TI  - Pore-scale statistics of flow and transport through porous media.
AB  - Flow in porous media is known to be largely affected by pore morphology. In this
      work, we investigate the effects of pore geometry on the transport and spatial
      correlations of flow through porous media in two distinct pore structures arising
      from three-dimensional assemblies of overlapping and nonoverlapping spheres.
      Using high-resolution direct numerical simulations (DNS), we perform Eulerian and
      Lagrangian analysis of the flow and transport characteristics in porous media. We
      show that the Eulerian velocity distributions change from nearly exponential to
      Gaussian distributions as porosity increases. A stretched exponential
      distribution can be used to represent this behavior for a wide range of
      porosities. Evolution of Lagrangian velocities is studied for the uniform
      injection rule. Evaluation of tortuosity and trajectory length distributions of
      each porous medium shows that the model of overlapping spheres results in higher
      tortuosity and more skewed trajectory length distributions compared to the model
      of nonoverlapping spheres. Wider velocity distribution and higher tortuosity for
      overlapping spheres model give rise to non-Fickian transport while transport in
      nonoverlapping spheres model is found to be Fickian. Particularly, for
      overlapping spheres model our analysis of first-passage time distribution shows
      that the transport is very similar to those observed for sandstone. Finally,
      using three-dimensional (3D) velocity field obtained by DNS at the pore-scale, we
      quantitatively show that despite the randomness of pore-space, the spatially
      fluctuating velocity field and the 3D pore-space distribution are strongly
      correlated for a range of porous media from relatively homogeneous monodisperse
      sphere packs to Castlegate sandstone.

PMID- 30110740
TI  - Electrostatic solitons and Alfven waves generated by streaming instability in
      electron-positron plasmas.
AB  - Electron-positron plasmas may be present in laboratory experiments and certain
      astrophysical environments. Due to the inertia symmetry there have been some
      debates about whether the nonlinear electrostatic solitons generated easily in
      electron-proton plasmas may develop in electron-positron plasmas. In this study
      we show the formation of electrostatic solitons and electromagnetic Alfven waves
      in extensive magnetized electron-positron plasma system generated by streaming
      instabilities based on electromagnetic particle simulations along with fluid
      theory analyses. In particular, the four-component beam-plasma system may lead to
      the formation of interlacing electron and positron solitons in the early
      evolution stage (say, t<20omega_{p}^{-1}, where omega_{p}^{} is the plasma
      frequency) and large-amplitude Alfven waves in the later phase (say,
      t>150omega_{p}^{-1}). The magnetic-field perturbations are generated by the beam
      and firehose-type instabilities associated with temperature anisotropy of
      T_{?}>T_{?} resulting from the parallel plasma heating by the electrostatic
      instability. It is shown that the growth rates and the dominant wavelengths of
      both electrostatic and electromagnetic instabilities are consistent with the
      fluid theory. The coexistence of electrostatic solitons and electromagnetic
      Alfven waves with significant magnetic field fluctuations in the same system is a
      unique feature of electron-positron plasmas and the unified theory behind the
      formation mechanisms is well addressed in the paper.

PMID- 30110741
TI  - Optimization of targeted node set in complex networks under percolation and
      selection.
AB  - Most of the existing methods for the robustness and targeted immunization
      problems can be viewed as greedy strategies, which are quite efficient but
      readily induce a local optimization. In this paper, starting from a percolation
      perspective, we develop two strategies, the relationship-related (RR) strategy
      and the prediction relationship (PR) strategy, to avoid a local optimum only
      through the investigation of interrelationships among nodes. Meanwhile, RR
      combines the sum rule and the product rule from explosive percolation, and PR
      holds the assumption that nodes with high degree are usually more important than
      those with low degree. In this manner our methods have a better capability to
      collapse or protect a network. The simulations performed on a number of networks
      also demonstrate their effectiveness, especially on large real-world networks
      where RR fragments each of them into the same size of the giant component;
      however, RR needs only less than 90% of the number of nodes which are necessary
      for the most excellent existing methods.

PMID- 30110742
TI  - Diffusion of a particle in the Gaussian random-energy landscape: Einstein
      relation and analytical properties of average velocity and diffusivity as
      functions of driving force.
AB  - We demonstrate that the Einstein relation for the diffusion of a particle in the
      random-energy landscape with the Gaussian density of states is an exclusive one
      dimensional property and does not hold in higher dimensions. We also consider the
      analytical properties of the particle velocity and diffusivity for the limit of
      weak driving force and establish a connection between these properties and
      dimensionality and spatial correlation of the random-energy landscape.

PMID- 30110743
TI  - Stability of gravity-capillary solitary waves on shallow water based on the fifth
      order Kadomtsev-Petviashvili equation.
AB  - Longitudinal and transverse instabilities of gravity-capillary solitary waves on
      shallow water are investigated based on the numerical analysis of the fifth-order
      Kadomtsev-Petviashvili (KP) equation, which describes the wave phenomena on
      shallow water where the relevant Bond number is less than and close to 1/3. Two
      dimensional (2D) depression gravity-capillary solitary waves are stable to
      longitudinal perturbations. 2D elevation gravity-capillary solitary waves are
      unstable to longitudinal perturbations and finally evolve into 2D depression
      gravity-capillary solitary waves. Three-dimensional (3D) finite-amplitude
      depression gravity-capillary solitary waves are stable to longitudinal
      perturbations. 3D finite-amplitude elevation gravity-capillary solitary waves are
      unstable to longitudinal perturbations and finally evolve into an oscillatory
      state between two different 3D finite-amplitude depression gravity-capillary
      solitary waves. 3D small-amplitude depression and elevation gravity-capillary
      solitary waves are unstable to dilation-type longitudinal perturbations and
      eventually evolve into an oscillatory state between two different 3D finite
      amplitude depression gravity-capillary solitary waves. 3D small-amplitude
      depression and elevation gravity-capillary solitary waves are unstable to
      contraction-type longitudinal perturbations and eventually become dispersed out
      toward still water surface. Finally, 2D depression and elevation gravity
      capillary solitary waves are unstable to transverse perturbations and eventually
      evolve into 3D finite-amplitude depression gravity-capillary solitary waves.
      Therefore, the only stable gravity-capillary solitary waves on shallow water are
      3D finite-amplitude depression gravity-capillary solitary waves. In particular,
      based on the linear stability analysis, a theoretical proof is presented for the
      long-wave transverse instability of 2D depression and elevation gravity-capillary
      solitary waves on shallow water.

PMID- 30110744
TI  - Using a reservoir computer to learn chaotic attractors, with applications to
      chaos synchronization and cryptography.
AB  - Using the machine learning approach known as reservoir computing, it is possible
      to train one dynamical system to emulate another. We show that such trained
      reservoir computers reproduce the properties of the attractor of the chaotic
      system sufficiently well to exhibit chaos synchronization. That is, the trained
      reservoir computer, weakly driven by the chaotic system, will synchronize with
      the chaotic system. Conversely, the chaotic system, weakly driven by a trained
      reservoir computer, will synchronize with the reservoir computer. We illustrate
      this behavior on the Mackey-Glass and Lorenz systems. We then show that trained
      reservoir computers can be used to crack chaos based cryptography and illustrate
      this on a chaos cryptosystem based on the Mackey-Glass system. We conclude by
      discussing why reservoir computers are so good at emulating chaotic systems.

PMID- 30110745
TI  - Topological data analysis of continuum percolation with disks.
AB  - We study continuum percolation with disks, a variant of continuum percolation in
      two-dimensional Euclidean space, by applying tools from topological data
      analysis. We interpret each realization of continuum percolation with disks as a
      topological subspace of [0,1]^{2} and investigate its topological features across
      many realizations. Specifically, we apply persistent homology to investigate
      topological changes as we vary the number and radius of disks, and we observe
      evidence that the longest persisting invariant is born at or near the percolation
      transition.

PMID- 30110746
TI  - Kicked Hall systems: Quantum-dynamical and spectral manifestations of generic
      superweak chaos.
AB  - Classical "kicked Hall systems" (KHSs), i.e., periodically kicked charges in the
      presence of uniform magnetic and electric fields that are perpendicular to each
      other and to the kicking direction, have been introduced and studied recently. It
      was shown that KHSs exhibit, under generic conditions, the phenomenon of
      "superweak chaos" (SWC), i.e., for small kick strength kappa a KHS behaves as if
      this strength were effectively kappa^{2} rather than kappa. Here we investigate
      quantum-dynamical and spectral manifestations of this generic SWC. We first
      derive general expressions for quantum effective Hamiltonians for the KHSs. We
      then show that the phenomenon of quantum antiresonance (QAR), i.e., "frozen"
      quantum dynamics with flat quasienergy (QE) bands, takes place for integer values
      of a scaled Planck constant h_{s} and under the same generic conditions for SWC.
      This appears to be the most generic occurrence of QAR in quantum systems. The
      vicinity of QAR is shown to correspond semiclassically to SWC. A global spectral
      manifestation of SWC is the fact that a scaled QE spectrum as function of h_{s},
      at fixed small value of kappa/h_{s}, features an approximately "doubled"
      structure. In the case of standard (cosine) potentials, this structure is that of
      a universal (parameters-independent) double Hofstadter butterfly. Also, for
      standard potentials and for small h_{s} (semiclassical regime), the evolution of
      the kinetic-energy expectation value exhibits a relatively slow quantum-diffusive
      behavior having universal features. These approximate spectral and quantum
      dynamical universalities agree with predictions from the effective Hamiltonian.

PMID- 30110747
TI  - Combined influence of hydrodynamics and chemotaxis in the distribution of
      microorganisms around spherical nutrient sources.
AB  - We study how the interaction between hydrodynamics and chemotaxis affects the
      colonization of nutrient sources by microorganisms. We use an individual-based
      model and perform probabilistic simulations to ascertain the impact of important
      environmental and motility characteristics on the spatial distribution of
      microorganisms around a spherical nutrient source. In general, we unveil four
      distinct regimes based on the distribution of the microorganisms: (i) strong
      surface colonization, (ii) rotary-diffusion-induced "off-surface" accumulation,
      (iii) a depletion zone in the spatial distribution, and (iv) no appreciable
      aggregation, with their occurrence being contingent on the relative strengths of
      hydrodynamic and chemotactic effects. More specifically, we show that the extent
      of surface colonization first increases, then reaches a plateau, and finally
      decreases as the nutrient availability is increased. We also show that surface
      colonization reduces monotonically as the mean run length of the chemotactic
      microorganisms increases. Our study provides insight into the interplay of two
      important mechanisms governing microorganism behavior near nutrient sources,
      isolates each of their effects, and thus offers greater predictability of this
      nontrivial phenomenon.

PMID- 30110748
TI  - Structural properties of the Jagla fluid.
AB  - The structural properties of the Jagla fluid are studied by Monte Carlo (MC)
      simulations, numerical solutions of integral equation theories, and the (semi
      analytical) rational-function approximation (RFA) method. In the latter case, the
      results are obtained from the assumption (supported by our MC simulations) that
      the Jagla potential and a potential with a hard core plus an appropriate
      piecewise constant function lead to practically the same cavity function. The
      predictions obtained for the radial distribution function, g(r), from this
      approach are compared against MC simulations and integral equations for the Jagla
      model, and also for the limiting cases of the triangle-well potential and the
      ramp potential, with a general good agreement. The analytical form of the RFA in
      Laplace space allows us to describe the asymptotic behavior of g(r) in a clean
      way and compare it with MC simulations for representative states with oscillatory
      or monotonic decay. The RFA predictions for the Fisher-Widom and Widom lines of
      the Jagla fluid are obtained.

PMID- 30110749
TI  - Fixed-density boundary conditions in overdamped Langevin simulations of diffusion
      in channels.
AB  - We consider the numerical integration of Langevin equations for particles in a
      channel, in the presence of boundary conditions fixing the concentration values
      at the ends. This kind of boundary condition appears, for instance, when
      considering the diffusion of ions in molecular channels, between the different
      concentrations at both sides of the cellular membrane. For this application the
      overdamped limit of Brownian motion (leading to a first order Langevin equation)
      is most convenient, but in previous works some difficulties associated with this
      limit were found for the implementation of the boundary conditions. We derive
      here an algorithm that, unlike previous attempts, does not require the simulation
      of particle reservoirs or the consideration of velocity variables or adjustable
      parameters. Simulations of Brownian particles in simple cases show that results
      agree perfectly with theory, both for the local concentration values and for the
      resulting particle flux in nonequilibrium situations. The algorithm is
      appropriate for the modeling of more complex ionic channels and, in general, for
      the treatment of analogous boundary conditions in other physical models using
      first order Langevin equations.

PMID- 30110750
TI  - Distribution of shortest path lengths in subcritical Erdos-Renyi networks.
AB  - Networks that are fragmented into small disconnected components are prevalent in
      a large variety of systems. These include the secure communication networks of
      commercial enterprises, government agencies, and illicit organizations, as well
      as networks that suffered multiple failures, attacks, or epidemics. The
      structural and statistical properties of such networks resemble those of
      subcritical random networks, which consist of finite components, whose sizes are
      nonextensive. Surprisingly, such networks do not exhibit the small-world property
      that is typical in supercritical random networks, where the mean distance between
      pairs of nodes scales logarithmically with the network size. Unlike supercritical
      networks whose structure has been studied extensively, subcritical networks have
      attracted relatively little attention. A special feature of these networks is
      that the statistical and geometric properties vary between different components
      and depend on their sizes and topologies. The overall statistics of the network
      can be obtained by a summation over all the components with suitable weights. We
      use a topological expansion to perform a systematic analysis of the degree
      distribution and the distribution of shortest path lengths (DSPL) on components
      of given sizes and topologies in subcritical Erdos-Renyi (ER) networks. From this
      expansion we obtain an exact analytical expression for the DSPL of the entire
      subcritical network, in the asymptotic limit. The DSPL, which accounts for all
      the pairs of nodes that reside on the same finite component (FC), is found to
      follow a geometric distribution of the form P_{FC}(L=l|L<infinity)=(1-c)c^{l-1},
      where c<1 is the mean degree. Using computer simulations we calculate the DSPL in
      subcritical ER networks of increasing sizes and confirm the convergence to this
      asymptotic result. We also obtain exact asymptotic results for the mean distance,
      <L>_{FC}, and for the standard deviation of the DSPL, sigma_{L,FC}, and show that
      the simulation results converge to these asymptotic results. Using the duality
      relations between subcritical and supercritical ER networks, we obtain the DSPL
      on the nongiant components of ER networks above the percolation transition.

PMID- 30110751
TI  - Localization due to topological stochastic disorder in active networks.
AB  - An active network is a prototype model in nonequilibrium statistical mechanics.
      It can represent, for example, a system with particles that have a self
      propulsion mechanism. Each node of the network specifies a possible location of a
      particle and its orientation. The orientation (which is formally like a spin
      degree of freedom) determines the self-propulsion direction. The bonds represent
      the possibility to make transitions: to hop between locations or to switch the
      orientation. In systems of experimental interest (Janus particles), the self
      propulsion is induced by illumination. An emergent aspect is the topological
      stochastic disorder (TSD). It is implied by the nonuniformity of the
      illumination. In technical terms the TSD reflects the local nonzero circulations
      (affinities) of the stochastic transitions. This type of disorder, unlike a
      nonhomogeneous magnetic field, is non-Hermitian and can lead to the emergence of
      a complex relaxation spectrum. It is therefore dramatically distinct from the
      conservative Anderson-type or Sinai-type disorder. We discuss the consequences of
      having TSD. In particular we illuminate three different routes to underdamped
      relaxation and show that localization plays a major role in the analysis.
      Implications of the bulk-edge correspondence principle are addressed too.

PMID- 30110752
TI  - Phase drift on networks of coupled crystal oscillators for precision timing.
AB  - Precise time dissemination and synchronization have been some of the most
      important technological tasks for several centuries. Since the early 1800s, it
      was realized that precise time-keeping devices having the same stable frequency
      and precisely synchronized can have important applications in navigation. In
      modern times, satellite-based global positioning and navigation systems such as
      the GPS use the same principle. However, even the most sophisticated satellite
      navigation equipment cannot operate in every environment. In response to this
      need, we present a computational and analytical study of a network-based model of
      a high-precision, inexpensive, coupled crystal oscillator system and timing
      (CCOST) device. A bifurcation analysis (carried out by the authors in a related
      publication) [Buono et al., SIAM J. Appl. Dyn. Syst. 17, 1310 (2018)1536
      004010.1137/16M1066154] of the network dynamics shows a wide variety of
      collective patterns, mainly various forms of discrete rotating waves and
      synchronization patterns. Results from computer simulations seem to indicate
      that, among all patterns, the standard traveling wave pattern in which
      consecutive crystals oscillate out of phase by 2pi/N, where N is the network
      size, leads to phase drift error that decreases as 1/N as opposed to 1/sqrt[N]
      for an uncoupled ensemble. The results should provide guidelines for future
      experiments, design, and fabrication tasks.

PMID- 30110753
TI  - Principle of maximum caliber and quantum physics.
AB  - MaxCal is a variational principle that can be used to infer distributions of
      paths in the phase space of dynamical systems. It has been successfully applied
      to different areas of classical physics, in particular statistical mechanics in
      and out of equilibrium. In this work, guided by the analogy of the formalism of
      MaxCal with that of the path integral formulation of quantum mechanics, we
      explore the extension of its applications to the realm of quantum physics, and
      show how the Lagrangians of both relativistic and nonrelativistic quantum fields
      can be built from MaxCal, with a suitable set of constraints. Related, the
      details of the constraints allow us to reinterpret the concept of inertia.

PMID- 30110754
TI  - Acoustic detection of electrostatic suppression of the Leidenfrost state.
AB  - At high temperatures, a droplet can rest on a cushion of its vapor (the
      Leidenfrost effect). Application of an electric field across the vapor gap
      fundamentally eliminates the Leidenfrost state by attracting liquid towards the
      surface. This study uses acoustic signature tracking to study electrostatic
      suppression of the Leidenfrost state on solid and liquid surfaces. It is seen
      that the liquid-vapor instabilities that characterize suppression on solid
      surfaces can be detected acoustically. This can be the basis for objective
      measurements of the threshold voltage and frequency required for suppression.
      Acoustic analysis provides additional physical insights that would be challenging
      to obtain with other measurements. On liquid surfaces, the absence of an acoustic
      signal indicates a different suppression mechanism (instead of instabilities).
      Acoustic signature tracking can also detect various boiling patterns associated
      with electrostatically assisted quenching. Overall, this work highlights the
      benefits of acoustics as a tool to better understand electrostatic suppression of
      the Leidenfrost state, and the resulting heat transfer enhancement.

PMID- 30110755
TI  - Self-organized system-size oscillation of a stochastic lattice-gas model.
AB  - The totally asymmetric simple exclusion process (TASEP) is a paradigmatic
      stochastic model for nonequilibrium physics, and has been successfully applied to
      describe active transport of molecular motors along cytoskeletal filaments.
      Building on this simple model, we consider a two-lane lattice-gas model that
      couples directed transport (TASEP) to diffusive motion in a semiclosed geometry,
      and simultaneously accounts for spontaneous growth and particle-induced shrinkage
      of the system's size. This particular extension of the TASEP is motivated by the
      question of how active transport and diffusion might influence length regulation
      in confined systems. Surprisingly, we find that the size of our intrinsically
      stochastic system exhibits robust temporal patterns over a broad range of growth
      rates. More specifically, when particle diffusion is slow relative to the
      shrinkage dynamics, we observe quasiperiodic changes in length. We provide an
      intuitive explanation for the occurrence of these self-organized temporal
      patterns, which is based on the imbalance between the diffusion and shrinkage
      speed in the confined geometry. Finally, we formulate an effective theory for the
      oscillatory regime, which explains the origin of the oscillations and correctly
      predicts the dependence of key quantities, such as the oscillation frequency, on
      the growth rate.

PMID- 30110756
TI  - Multistable dissipative breathers and collective states in SQUID Lieb
      metamaterials.
AB  - A SQUID (Superconducting QUantum Interference Device) metamaterial on a Lieb
      lattice with nearest-neighbor coupling supports simultaneously stable dissipative
      breather families which are generated through a delicate balance of input power
      and intrinsic losses. Breather multistability is possible due to the peculiar
      snaking flux amplitude-frequency curve of single dissipative-driven SQUIDs, which
      for relatively high sinusoidal flux field amplitudes exhibits several stable and
      unstable solutions in a narrow frequency band around resonance. These breathers
      are very weakly interacting with each other, while multistability regimes with a
      different number of simultaneously stable breathers persist for substantial
      intervals of frequency, flux field amplitude, and coupling coefficients.
      Moreover, the emergence of chimera states as well as temporally chaotic states
      exhibiting spatial homogeneity within each sublattice of the Lieb lattice is
      demonstrated. The latter of the states emerge through an explosive hysteretic
      transition resembling explosive synchronization that has been reported before for
      various networks of oscillators.

PMID- 30110757
TI  - Detecting critical transitions in the case of moderate or strong noise by
      binomial moments.
AB  - Detecting critical transitions in the case of moderate or strong noise
      (collectively referred to as big noise) is challenging, since such noise can make
      a critical transition point far from the bifurcation point, leading to the
      failure of traditional small-noise methods. To handle this tough issue, we first
      transform a generic noisy system into a linear set of binomial moment equations
      (BMEs). Then, we can solve a closed set of BMEs obtained by truncation and use
      the resulting binomial moments to reconstruct a joint probability distribution of
      the state variables of the original system. Third, we derive a leading indicator
      from the closed set of BMEs. Importantly, the reconstructed distribution
      determines the way of critical transition (i.e., critical transition is
      distribution transition rather than state transition in the strong-noise case) as
      the system comes close to the critical transition point, whereas the derived
      indicator anticipates when the distribution transition occurs. Our theory has
      broad applications, and artificial and data examples exhibit its power.

PMID- 30110758
TI  - Propagation of interacting diseases on multilayer networks.
AB  - The study on the dynamics of interacting diseases has attracted considerable
      attention in recent years. This paper proposes a model for two interacting
      epidemics spreading concurrently on a two-layer network, where both the epidemic
      thresholds and the dynamics of disease outbreaks are investigated. The analytical
      expression of the epidemic threshold shows strong coupling between the two
      interacting epidemics. Moreover, two metrics, the maximum prevalence and the
      highest spreading speed, are proposed to describe the outbreak process.
      Theoretical analysis together with extensive simulations illustrate the functions
      of various factors, including the network topological parameters, percentage of
      overlapped network links, vulnerable individuals, and the reciprocity of the two
      diseases. It is found that the seemingly important factor, i.e., the percentage
      of overlapped links, possesses no effect on the propagation, while the frequently
      overlooked factor, i.e., the percentage of vulnerable individuals, has
      significant effects. For the interaction of the two diseases, the recovery state
      of one disease is more influential than the other in both the mutually enhanced
      and the mutually impaired situations.

PMID- 30110759
TI  - Kinetics of deposition in the diffusion-controlled limit.
AB  - The adsorption of particles diffusing in a half space bounded by the substrate
      and irreversibly sticking to the substrate upon contacts is investigated. We show
      that when absorbing particles are planar disks diffusing in the three-dimensional
      half space, the coverage approaches its saturated "jamming" value as t^{-1} in
      the large time limit (generally as t^{-1/(d-1)} when the substrate is d
      dimensional and d>1, and as e^{-t/ln(t)} when d=1). We also analyze the
      asymptotic behavior when particles are spherical and when particles are planar
      aligned squares.

PMID- 30110760
TI  - Quantum mechanical response to a driven Caldeira-Leggett bath.
AB  - We determine the frequency-dependent response characteristics of a quantum system
      to a driven Caldeira-Leggett bath. The bath degrees of freedom are explicitly
      driven by an external time-dependent force, in addition to the direct time
      dependent forcing of the system itself. After general considerations of driven
      Caldeira-Leggett baths, we consider the Rubin model of a chain of quantum
      particles coupled by linear springs as an important model of a quantum
      dissipative system. We show that in the presence of time-dependent driving of the
      chain, this model can be mapped to a quantum system which couples to a driven
      Caldeira-Leggett bath. The effect of the bath driving is captured by a time
      dependent force on the central system, which is, in principle, non-Markovian in
      nature. We study two specific examples, the exactly solvable case of a harmonic
      potential and a quantum two-state system for which we assume a weak system-bath
      coupling. We evaluate the dynamical response to a periodic driving of the system
      and the bath. The dynamic susceptibility is shown to be altered qualitatively by
      the bath drive: The dispersive part is enhanced at low frequencies and acquires a
      maximum at zero frequency. The absorptive part develops a shoulder-like behavior
      in this frequency regime. These features seem to be generic for quantum systems
      in a driven Caldeira-Leggett bath.

PMID- 30110761
TI  - Coulomb-force-mediated heat transfer in the near field: Geometric effect.
AB  - It has been shown recently that the Coulomb part of electromagnetic interactions
      is more important than the transverse propagation waves for the near-field
      enhancement of heat transfer between metal objects at a distance of order
      nanometers. Here we present a theory focusing solely on the Coulomb potential
      between electrons hopping among tight-binding sites. When the relevant systems
      are reduced to very small geometry, for example, a single site, the enhancement
      is much higher compared to a collection of them packed within a distance of a few
      A. We credit this to the screening effect. This result may be useful in designing
      metal-based metamaterials to enhance heat transfer much higher.

PMID- 30110763
TI  - Exact ground states of the Kaya-Berker model.
AB  - Here we study the two-dimensional Kaya-Berker model, with a site occupancy p of
      one sublattice, by using a polynomial-time exact ground-state algorithm. Thus, we
      were able to obtain T=0 results in exact equilibrium for rather large system
      sizes up to 777^{2} lattice sites. We obtained the sublattice magnetization and
      the corresponding Binder parameter. We found a critical point p_{c}=0.64(1)
      beyond which the sublattice magnetization vanishes. This is clearly smaller than
      previous results which were obtained by using nonexact approaches for much
      smaller systems. For each realization we also created minimum-energy domain walls
      from two ground-state calculations, for periodic and antiperiodic boundary
      conditions. The analysis of the mean and the variance of the domain-wall energy
      shows that there is no thermodynamic stable spin-glass phase at nonzero
      temperature, in contrast to previous claims about this model. For large values of
      p, the standard deviation of the domain-wall decreases with the system size like
      a power law with exponent roughly theta?-0.1, which is different from the
      standard two-dimensional Ising spin glass where theta?-0.29.

PMID- 30110762
TI  - Solution of the Crow-Kimura model with changing population size and Allee effect.
AB  - The Crow-Kimura model is commonly used in the modeling of genetic evolution in
      the presence of mutations and associated selection pressures. We consider a
      modified version of the Crow-Kimura model, in which population sizes are not
      fixed and Allee saturation effects are present. We demonstrate the evolutionary
      dynamics in this system through an analytical approach, examining both symmetric
      and single-peak fitness landscape cases. Especially interesting are the dynamics
      of the populations near extinction. A special version of the model with
      saturation and degradation on the single-peak fitness landscape is investigated
      as a candidate of the Allee effect in evolution, revealing reduction tendencies
      of excessively large populations, and extinction tendencies for small
      populations. The analytical solutions for these dynamics are presented with
      accuracy O(1/N), where N is the number of nucleotides in the genome.

PMID- 30110764
TI  - Optimized bacteria are environmental prediction engines.
AB  - Experimentalists observe phenotypic variability even in isogenic bacteria
      populations. We explore the hypothesis that in fluctuating environments this
      variability is tuned to maximize a bacterium's expected log-growth rate,
      potentially aided by epigenetic (all inheritable nongenetic) markers that store
      information about past environments. Crucially, we assume a time delay between
      sensing and action, so that a past epigenetic marker is used to generate the
      present phenotypic variability. We show that, in a complex, memoryful
      environment, the maximal expected log-growth rate is linear in the instantaneous
      predictive information-the mutual information between a bacterium's epigenetic
      markers and future environmental states. Hence, under resource constraints,
      optimal epigenetic markers are causal states-the minimal sufficient statistics
      for prediction-or lossy approximations thereof. We propose new theoretical
      investigations into and new experiments on bacteria phenotypic bet-hedging in
      fluctuating complex environments.

PMID- 30110765
TI  - Criticality of the nonconservative earthquake model on random spatial networks.
AB  - We study the nonconservative earthquake model on random spatial networks. The
      spatial networks are composed of sites on a two-dimensional (2D) plane which are
      connected locally. Differently from a regular lattice, the locations of sites are
      modeled in the way that sites are randomly placed on the plane. Using the same
      connectivity degree as a 2D lattice, however, the spatial network cannot exhibit
      critical earthquake behavior. Mimicking long range energy transfer, the
      connection radius is increased and the connectivity degree of the spatial network
      is increased. Then we show that the model exhibits self-organized criticality.
      The mechanism of the structural effect is presented. The spatial network includes
      many modules when connectivity degree is very small. The effect of modular
      structure on the avalanche dynamics is to limit the spreading of avalanches in
      the whole network. When the connectivity degree is larger, the long range energy
      transfer can overcome the effect of local modularity and criticality can be
      reached.

PMID- 30110766
TI  - Structural crossover in a model fluid exhibiting two length scales: Repercussions
      for quasicrystal formation.
AB  - We investigate the liquid state structure of the two-dimensional model introduced
      by Barkan et al. [Phys. Rev. Lett. 113, 098304
      (2014)10.1103/PhysRevLett.113.098304], which exhibits quasicrystalline and other
      unusual solid phases, focusing on the radial distribution function g(r) and its
      asymptotic decay r->infinity. For this particular model system, we find that as
      the density is increased there is a structural crossover from damped oscillatory
      asymptotic decay with one wavelength to damped oscillatory asymptotic decay with
      another distinct wavelength. The ratio of these wavelengths is ~1.932. Following
      the locus in the phase diagram of this structural crossover leads directly to the
      region where quasicrystals are found. We argue that identifying and following
      such a crossover line in the phase diagram towards higher densities where the
      solid phase(s) occur is a good strategy for finding quasicrystals in a wide
      variety of systems. We also show how the pole analysis of the asymptotic decay of
      equilibrium fluid correlations is intimately connected with the nonequilibrium
      growth or decay of small-amplitude density fluctuations in a bulk fluid.

PMID- 30110767
TI  - Random sequential adsorption on mobile patches.
AB  - An extension of the random sequential adsorption model has been proposed
      recently, motivated by the coverage of oil droplets by DNA-functionalized
      colloidal particles. Particles arrive to a flat substrate with a uniform flux F
      but they can only adsorb on patches. Patches diffuse on the substrate with a
      diffusion coefficient D if they are free and they remain immobile when attached
      to an adsorbed particle. The adsorption is considered irreversible and particles
      cannot adsorb on top of each other. Thus, the system reaches a jammed state,
      consisting of a monolayer where no more particles can adsorb. We performed Monte
      Carlo simulations to study the adsorption kinetics and jammed-state morphology on
      a one-dimensional lattice. We show that, while the time-dependence of the
      coverage depends on F and D, the jammed-state coverage depends solely on the
      ratio F/D. This result is grasped by a simple mean-field calculation. We also
      report two different regimes for the functional dependence of the jammed-state
      coverage on the size of the particles, for low and high density of patches.

PMID- 30110769
TI  - One-dimensional superdiffusive heat propagation induced by optical phonon-phonon
      interactions.
AB  - One-dimensional anomalous heat propagation is usually characterized by a Levy
      walk superdiffusive spreading function with two side peaks located on the fronts
      due to the finite velocity of acoustic phonons. In the case when the acoustic
      phonons vanish, e.g., due to the phonon-lattice interactions such that the
      system's momentum is not conserved, the side peaks will disappear and a normal
      Gaussian diffusive heat-propagating behavior will be observed. Here we show that
      there exists another new type of superdiffusive, non-Gaussian heat propagation
      but without side peaks in a typical nonacoustic, momentum-nonconserving system.
      It implies that thermal transport in this system disobeys the Fourier law, in
      clear contrast with the existing theoretical predictions. The underlying
      mechanism is related to an effect of optical phonon-phonon interactions. These
      findings may open a new avenue for further exploring thermal transport in low
      dimensions.

PMID- 30110768
TI  - Configuration model for correlation matrices preserving the node strength.
AB  - Correlation matrices are a major type of multivariate data. To examine properties
      of a given correlation matrix, a common practice is to compare the same quantity
      between the original correlation matrix and reference correlation matrices, such
      as those derived from random matrix theory, that partially preserve properties of
      the original matrix. We propose a model to generate such reference correlation
      and covariance matrices for the given matrix. Correlation matrices are often
      analyzed as networks, which are heterogeneous across nodes in terms of the total
      connectivity to other nodes for each node. Given this background, the present
      algorithm generates random networks that preserve the expectation of total
      connectivity of each node to other nodes, akin to configuration models for
      conventional networks. Our algorithm is derived from the maximum entropy
      principle. We will apply the proposed algorithm to measurement of clustering
      coefficients and community detection, both of which require a null model to
      assess the statistical significance of the obtained results.

PMID- 30110770
TI  - Dismantling efficiency and network fractality.
AB  - In network dismantling, a minimal set of nodes is identified whose removal breaks
      the network into small components of subextensive size. Because finding the
      optimal set of nodes is an NP-hard problem, several heuristic algorithms have
      been developed as alternative methods, for instance, the so-called belief
      propagation-based decimation (BPD) algorithm and the collective influence (CI)
      algorithm. Here, we test the performance of these algorithms and analyze them in
      terms of the fractality of the network. Networks are classified into two types:
      fractal and nonfractal networks. Real-world examples include the World Wide Web
      and the Internet at the autonomous system level, respectively. They have
      different ratios of long-range shortcuts to short-range ones. We find that the
      BPD algorithm works more efficiently than the CI algorithm no matter whether a
      network is fractal or not. On the other hand, the CI algorithm works better on
      nonfractal networks than on fractal networks. We construct diverse fractal and
      nonfractal model networks by controlling parameters such as the degree exponent,
      shortcut number, and system size and investigate how the performance of the two
      algorithms depends on structural features.

PMID- 30110771
TI  - Effects of thermal fluctuations in the fragmentation of a nanoligament.
AB  - We study the effects of thermally induced capillary waves in the fragmentation of
      a liquid ligament into multiple nanodroplets. Our numerical implementation is
      based on a fluctuating lattice Boltzmann (LB) model for nonideal multicomponent
      fluids, including nonequilibrium stochastic fluxes mimicking the effects of
      molecular forces at the nanoscales. We quantitatively analyze the statistical
      distribution of the breakup times and the droplet volumes after the fragmentation
      process at changing the two relevant length scales of the problem, i.e., the
      thermal length scale and the ligament size. The robustness of the observed
      findings is also corroborated by quantitative comparisons with the predictions of
      sharp interface hydrodynamics. Beyond the practical importance of our findings
      for nanofluidic engineering devices, our study also explores a novel application
      of LB in the realm of nanofluidic phenomena.

PMID- 30110772
TI  - Influence of flexoelectric effect on the Freedericksz transition in chiral
      nematic liquid crystals.
AB  - Electric field driven Freedericksz transition in chiral nematic (cholesteric)
      planar liquid crystal cell is studied in the presence of flexoelectric effect. An
      inhomogeneity of electric field and finiteness of anchoring energy are
      considered. The extra contribution to the electric field induced by
      flexoelectricity is taken into account as well as the common contribution arising
      from the applied voltage U. Equilibrium director distribution is obtained in
      dependence on voltage and flexoelectric coefficients by numerical minimization of
      the free energy. The threshold voltage was found to decrease with the increase of
      the flexoelectric coefficients within the range of high flexoelectric
      coefficients. Thus flexoelectricity promotes the transition. The orientational
      structure becomes asymmetric about the center of the cell due to
      flexoelectricity, even in the case of symmetric boundary conditions. The
      equilibrium structure was also shown to be different for U>0 and U<0. It was
      found, that for sufficiently high flexoelectric coefficients the director
      distribution can be described by a simple function. In this case the planar
      helicoidal structure transfers into a hybrid-aligned one as the voltage
      increases. This transformation may form the basis for new flexoelectricity-based
      switching devices. The nonmonotonic behavior of threshold voltage can be observed
      in the case of small flexoelectric coefficients. An analytical form of the
      stability conditions was obtained for the planar helicoidal configuration. We
      have shown that the Freedericksz transition can be either continuous or
      discontinuous depending on the material constants and thickness of the liquid
      crystal cell.

PMID- 30110773
TI  - Zipf and Heaps laws from dependency structures in component systems.
AB  - Complex natural and technological systems can be considered, on a coarse-grained
      level, as assemblies of elementary components: for example, genomes as sets of
      genes or texts as sets of words. On one hand, the joint occurrence of components
      emerges from architectural and specific constraints in such systems. On the other
      hand, general regularities may unify different systems, such as the broadly
      studied Zipf and Heaps laws, respectively concerning the distribution of
      component frequencies and their number as a function of system size. Dependency
      structures (i.e., directed networks encoding the dependency relations between the
      components in a system) were proposed recently as a possible organizing
      principles underlying some of the regularities observed. However, the
      consequences of this assumption were explored only in binary component systems,
      where solely the presence or absence of components is considered, and multiple
      copies of the same component are not allowed. Here we consider a simple model
      that generates, from a given ensemble of dependency structures, a statistical
      ensemble of sets of components, allowing for components to appear with any
      multiplicity. Our model is a minimal extension that is memoryless and therefore
      accessible to analytical calculations. A mean-field analytical approach
      (analogous to the "Zipfian ensemble" in the linguistics literature) captures the
      relevant laws describing the component statistics as we show by comparison with
      numerical computations. In particular, we recover a power-law Zipf rank plot,
      with a set of core components, and a Heaps law displaying three consecutive
      regimes (linear, sublinear, and saturating) that we characterize quantitatively.

PMID- 30110774
TI  - Single equalizer strategy with no information transfer for conflict escalation.
AB  - In an iterated two-person game, for instance prisoner's dilemma or the snowdrift
      game, there exist strategies that force the payoffs of the opponents to be equal.
      These equalizer strategies form a subset of the more general zero-determinant
      strategies that unilaterally set the payoff of an opponent. A challenge in the
      attempts to understand the role of these strategies in the evolution of animal
      behavior is the lack of iterations in the fights for mating opportunities or
      territory control. We show that an arbitrary two-parameter strategy may possess a
      corresponding equalizer strategy which produces the same result: statistics of
      the fight outcomes in the contests with competitors are the same for each of
      these two strategies. Therefore, analyzing only the equalizer strategy space may
      be sufficient to predict animal behavior if nature, indeed, reduces
      (marginalizes) complex strategies to equalizer strategy space. The work's main
      finding is that there is a unique equalizer strategy that predicts fight outcomes
      without symmetric cooperation responses. The lack of symmetric cooperation
      responses is a common trait in conflict escalation contests that generally
      require a clear winner. In addition, this unique strategy does not assess
      information of the opponent's state. The method bypasses the standard analysis of
      evolutionary stability. The results fit well the observations of combat between
      male bowl and doily spiders and support an empirical assumption of the war of
      attrition model that the species use only information regarding their own state
      during conflict escalation.

PMID- 30110775
TI  - Topological critical slowing down: Variations on a toy model.
AB  - Numerical simulations of lattice quantum field theories whose continuum
      counterparts possess classical solutions with nontrivial topology face a severe
      critical slowing down as the continuum limit is approached. Standard Monte Carlo
      algorithms develop a loss of ergodicity, with the system remaining frozen in
      configurations with fixed topology. We analyze the problem in a simple toy model,
      consisting of the path integral formulation of a quantum mechanical particle
      constrained to move on a circumference. More specifically, we implement for this
      toy model various techniques which have been proposed to solve or alleviate the
      problem for more complex systems, like non-Abelian gauge theories, and compare
      them both in the regime of low temperature and in that of very high temperature.
      Among the various techniques, we propose an alternative algorithm which
      completely solves the freezing problem, but unfortunately is specifically
      tailored for this particular model and not easily exportable to more complex
      systems.

PMID- 30110776
TI  - Robustness of optimal transport in disordered interacting many-body networks.
AB  - The robustness of quantum transport under various perturbations is analyzed in
      disordered interacting many-body systems, which are constructed from the embedded
      Gaussian random matrix ensembles (EGEs). The transport efficiency can be enhanced
      drastically, if centrosymmetry (csEGE) is imposed. When the csEGE is perturbed
      with an ordinary EGE, the transport efficiency in the optimal cases is reduced
      significantly, while in the suboptimal cases the changes are less pronounced.
      Qualitatively the same behavior is observed, when parity and centrosymmetry are
      broken by block perturbations. Analyzing the influence of the environment
      coupling, optimal transport is observed at a certain coupling strength, while too
      weak and too strong coupling reduce the transport. Taking into account the
      effects of decoherence, in the EGE the transport efficiency approaches its
      maximum at a finite nonzero decoherence strength (environment-assisted
      transport). In the csEGE the efficiency decays monotonically with the decoherence
      but is always larger than in the EGE.

PMID- 30110777
TI  - Steady thermocapillary migration of a droplet in a uniform temperature gradient
      combined with a radiation energy source at large Marangoni numbers.
AB  - Steady thermocapillary droplet migration in a uniform temperature gradient
      combined with a radiation energy source at large Reynolds and Marangoni numbers
      is studied. To reach a terminal quasisteady process, the magnitude of the
      radiation energy source is required to preserve the conservative integral thermal
      flux across the surface. Under a quasisteady state assumption, an analytical
      result for the steady thermocapillary migration of a droplet at large Reynolds
      and Marangoni numbers is derived by using the method of matched asymptotic
      expansions. It is shown that the thermocapillary droplet migration speed
      increases as the Marangoni number increases, while a radiation energy source with
      a sine square dependence is provided.

PMID- 30110778
TI  - Isotropic-nematic transition of self-propelled rods in three dimensions.
AB  - Using overdamped Brownian dynamics simulations we investigate the isotropic
      nematic (IN) transition of self-propelled rods in three spatial dimensions. For
      two well-known model systems (Gay-Berne potential and hard spherocylinders) we
      find that turning on activity moves to higher densities the phase boundary
      separating an isotropic phase from a (nonpolar) nematic phase. This active IN
      phase boundary is distinct from the boundary between isotropic and polar-cluster
      states previously reported in two-dimensional simulation studies and, unlike the
      latter, is not sensitive to the system size. We thus identify a generic feature
      of anisotropic active particles in three dimensions.

PMID- 30110779
TI  - Spectral energy scaling in precessing turbulence.
AB  - We study precessing turbulence, which appears in several geophysical and
      astrophysical systems, by direct numerical simulations of homogeneous turbulence
      where precessional instability is triggered due to the imposed background flow.
      We show that the time development of kinetic energy K occurs in two main phases
      associated with different flow topologies: (i) an exponential growth
      characterizing three-dimensional turbulence dynamics and (ii) nonlinear
      saturation during which K remains almost time independent, the flow becoming
      quasi-two-dimensional. The latter stage, wherein the development of K remains
      insensitive to the initial state, shares an important common feature with other
      quasi-two-dimensional rotating flows such as rotating Rayleigh-Benard convection,
      or the large atmospheric scales: in the plane k_{?}=0, i.e., the plane associated
      to an infinite wavelength in the direction parallel to the principal rotation
      axis, the kinetic energy spectrum scales as k_{?}^{-3}. We show that this power
      law is observed for wave numbers ranging between the Zeman "precessional" and
      "rotational" scales, k_{S}^{-1} and k_{Omega}^{-1}, respectively, at which the
      associated background shear or inertial timescales are equal to the eddy turnover
      time. In addition, an inverse cascade develops for (k_{?},k)<k_{S}, and the
      spherically averaged kinetic energy spectrum exhibits a k^{-2} inertial scaling
      for k_{S}<k<k_{Omega}.

PMID- 30110780
TI  - Robustness of chimera states in nonlocally coupled networks of nonidentical
      logistic maps.
AB  - We investigate the dynamics of nonlocally coupled time-discrete maps with
      emphasis on the occurrence and robustness of chimera states. These peculiar,
      hybrid states are characterized by a coexistence of coherent and incoherent
      regions. We consider logistic maps coupled on a one-dimensional ring with finite
      coupling radius. Domains of chimera existence form different tongues in the
      parameter space of coupling range and coupling strength. For a sufficiently large
      coupling strength, each tongue refers to a wave number describing the structure
      of the spatial profile. We also analyze the period-adding scheme within these
      tongues and multiplicity of period solutions. Furthermore, we study the
      robustness of chimeras with respect to parameter inhomogeneities and find that
      these states persist for different widths of the parameter distribution. Finally,
      we explore the spatial structure of the chimera using a spatial correlation
      function.

PMID- 30110781
TI  - Estimating stable and unstable sets and their role as transport barriers in
      stochastic flows.
AB  - We consider the situation of a large-scale stationary flow subjected to small
      scale fluctuations. Assuming that the stable and unstable manifolds of the large
      scale flow are known, we quantify the mean behavior and stochastic fluctuations
      of particles close to the unperturbed stable and unstable manifolds and their
      evolution in time. The mean defines a smooth curve in physical space, while the
      variance provides a time- and space-dependent quantitative estimate where
      particles are likely to be found. This allows us to quantify transport properties
      such as the expected volume of mixing as the result of the stochastic
      fluctuations of the transport barriers. We corroborate our analytical findings
      with numerical simulations in both compressible and incompressible flow
      situations. We moreover demonstrate the intimate connection of our results with
      finite-time Lyapunov exponent fields, and with spatial mixing regions.

PMID- 30110782
TI  - Energy-speed-accuracy relation in complex networks for biological discrimination.
AB  - Discriminating between correct and incorrect substrates is a core process in
      biology, but how is energy apportioned between the conflicting demands of
      accuracy (MU), speed (sigma), and total entropy production rate (P)? Previous
      studies have focused on biochemical networks with simple structure or relied on
      simplifying kinetic assumptions. Here, we use the linear framework for timescale
      separation to analytically examine steady-state probabilities away from
      thermodynamic equilibrium for networks of arbitrary complexity. We also introduce
      a method of scaling parameters that is inspired by Hopfield's treatment of
      kinetic proofreading. Scaling allows asymptotic exploration of high-dimensional
      parameter spaces. We identify in this way a broad class of complex networks and
      scalings for which the quantity sigmaln(MU)/P remains asymptotically finite
      whenever accuracy improves from equilibrium, so that MU_{eq}/MU->0. Scalings
      exist, however, even for Hopfield's original network, for which sigmaln(MU)/P is
      asymptotically infinite, illustrating the parametric complexity. Outside the
      asymptotic regime, numerical calculations suggest that, under more restrictive
      parametric assumptions, networks satisfy the bound, sigmaln(MU/MU_{eq})/P<1, and
      we discuss the biological implications for discrimination by ribosomes and DNA
      polymerase. The methods introduced here may be more broadly useful for analyzing
      complex networks that implement other forms of cellular information processing.

PMID- 30110783
TI  - Kardar-Parisi-Zhang growth on one-dimensional decreasing substrates.
AB  - Recent experimental works on one-dimensional (1D) circular Kardar-Parisi-Zhang
      (KPZ) systems whose radii decrease in time have reported controversial
      conclusions about the statistics of their interfaces. Motivated by this, here we
      investigate several one-dimensional KPZ models on substrates whose size changes
      in time as L(t)=L_{0}+omegat, focusing on the case omega<0. From extensive
      numerical simulations, we show that for L_{0}?1 there exists a transient regime
      in which the statistics is consistent with that of flat KPZ systems (the omega=0
      case), for both omega<0 and omega>0. Actually, for a given model, L_{0} and
      |omega|, we observe that a difference between ingrowing (omega<0) and outgrowing
      (omega>0) systems arises only at long times (t~t_{c}=L_{0}/|omega|), when the
      expanding surfaces cross over to the statistics of curved KPZ systems, whereas
      the shrinking ones become completely correlated. A generalization of the Family
      Vicsek scaling for the roughness of ingrowing interfaces is presented. Our
      results demonstrate that a transient flat statistics is a general feature of
      systems starting with large initial sizes, regardless of their curvature. This is
      consistent with their recent observation in ingrowing turbulent liquid crystal
      interfaces, but it is in contrast with the apparent observation of curved
      statistics in colloidal deposition at the edge of evaporating drops. A possible
      explanation for this last result, as a consequence of the very small number of
      monolayers analyzed in this experiment, is given. This is illustrated in a
      competitive growth model presenting a few-monolayer transient and an asymptotic
      behavior consistent, respectively, with the curved and flat statistics.

PMID- 30110784
TI  - Management of matter-wave solitons in Bose-Einstein condensates with time
      dependent atomic scattering length in a time-dependent parabolic complex
      potential.
AB  - In this paper, we consider a Gross-Pitaevskii (GP) equation with a time-dependent
      nonlinearity and a spatiotemporal complex linear term which describes the
      dynamics of matter-wave solitons in Bose-Einstein condensates (BECs) with time
      dependent interatomic interactions in a parabolic potential in the presence of
      feeding or loss of atoms. We establish the integrability conditions under which
      analytical solutions describing the modulational instability and the propagation
      of both bright and dark solitary waves on a continuous wave background are
      obtained. The obtained integrability conditions also appear as the conditions
      under which the solitary waves of the BECs can be managed by controlling the
      functional gain or loss parameter. For specific BECs, the dynamics of bright and
      dark solitons are investigated analytically through the found exact solutions of
      the GP equation. Our results show that under the integrability conditions, the
      gain or loss parameter of the GP equation can be used to manage the motion of
      both bright and dark solitons. We show that for BECs with loss (gain) of atoms,
      the bright and dark solitons during their propagation have a compression
      (broadening) in their width. Furthermore, under a safe range of parameters and
      under the integrability conditions, it is possible to squeeze a bright soliton of
      BECs with loss of atoms into the assumed peak matter density, which can provide
      an experimental tool for investigating the range of validity of the 1D GP
      equation. Our results also reveal that under the conditions of the solitary wave
      management, neither the injection or the ejection of atoms from the condensate
      affects the soliton peak during its propagation.

PMID- 30110785
TI  - Two-dimensional structures of electron bunches in relativistic plasma cavities.
AB  - The spatial structure of an ultralow-emittance electron bunch in a plasma
      wakefield blowout regime is studied. The full Lienard-Wiechert potentials are
      considered for mutual interparticle interactions in the framework of the
      equilibrium slice model. This model uses the quasistatic theory which allows one
      to solve the Lienard-Wiechert potentials without knowledge of the electrons'
      history. The equilibrium structure we find is similar to already observed
      hexagonal lattices but shows topological defects. Scaling laws for interparticle
      distances are obtained from numerical simulations and analytical estimations.

PMID- 30110786
TI  - Multiple structural transitions in interacting networks.
AB  - Many real-world systems can be modeled as interconnected multilayer networks,
      namely, a set of networks interacting with each other. Here, we present a
      perturbative approach to study the properties of a general class of
      interconnected networks as internetwork interactions are established. We reveal
      multiple structural transitions for the algebraic connectivity of such systems,
      between regimes in which each network layer keeps its independent identity or
      drives diffusive processes over the whole system, thus generalizing previous
      results reporting a single transition point. Furthermore, we show that, at first
      order in perturbation theory, the growth of the algebraic connectivity of each
      layer depends only on the degree configuration of the interaction network
      (projected on the respective Fiedler vector), and not on the actual interaction
      topology. Our findings can have important implications in the design of robust
      interconnected networked systems, particularly in the presence of network layers
      whose integrity is more crucial for the functioning of the entire system. We
      finally show results of perturbation theory applied to the adjacency matrix of
      the interconnected network, which can be useful to characterize percolation
      processes on such systems.

PMID- 30110787
TI  - Sinking in a bed of grains activated by shearing.
AB  - We show how a weak force f enables intruder motion through dense granular
      materials subject to external mechanical excitations, in the present case,
      stepwise shearing. A force acts on a Teflon disk in a two-dimensional system of
      photoelastic disks. This force is much smaller than the smallest force needed to
      move the disk without any external excitation. In a cycle, the material plus
      intruder are sheared quasistatically from gamma=0 to gamma_{max}, and then
      backwards to gamma=0. During various cycle phases, fragile and jammed states
      form. Net intruder motion delta occurs during fragile periods generated by shear
      reversals. delta per cycle, e.g., the quasistatic rate c, is constant, linearly
      dependent on gamma_{max} and f. It vanishes as c?(phi_{c}-phi)^{a}, with a?3 and
      phi_{c}?phi_{J}, reflecting the stiffening of granular systems under shear [J.
      Ren, J. A. Dijksman, and R. P. Behringer, Phys. Rev. Lett. 110, 018302
      (2013)]PRLTAO0031-900710.1103/PhysRevLett.110.018302 as phi->phi_{J}. The
      intruder motion induces large-scale grain circulation. In the intruder frame,
      this motion is a granular analog to fluid flow past a cylinder, where f is the
      drag force exerted by the flow.

PMID- 30110788
TI  - Cylinder morphology of a stretched and twisted ribbon.
AB  - A rich zoology of morphologies emerges from a simple stretched and twisted
      elastic ribbon. Despite a lot of interest, all the observed shapes are not
      quantitatively described. This is the case of the cylindrical shape that prevails
      at large tension and twist, which emerges from a transverse buckling instability
      of the helicoid. Here, we propose a simple description of this cylindrical shape.
      By comparing its energy to the energy of other configurations, helicoidal and
      facetted, we are able to determine its location on the tension-twist phase
      diagram. The theoretical predictions are in good quantitative agreement with the
      experimental results and complement previous results from linear stability
      analysis.

PMID- 30110790
TI  - Classical density functional theory, unconstrained crystallization, and
      polymorphic behavior.
AB  - While in principle, classical density functional theory (cDFT) should be a
      powerful tool for the study of crystallization, in practice this has not so far
      been the case. Progress has been hampered by technical problems which have
      plagued the study of the crystalline systems using the most sophisticated
      fundamental measure theory models. In this paper, the reasons for the
      difficulties are examined and it is proposed that the tensor functionals
      currently favored are in fact numerically unstable. By reverting to an older,
      more heuristic model it is shown that all of the technical difficulties are
      eliminated. Application to a Lennard-Jones fluid results in a demonstration of
      power of cDFT to describe crystallization in a highly inhomogeneous system.
      First, we show that droplets attached to a slightly hydrophobic wall crystallize
      spontaneously upon being quenched. The resulting crystallites are clearly faceted
      structures and are predominantly HCP structures. In contrast, droplets in a fully
      periodic calculational cell remain stable to lower temperatures and eventually
      show the same spontaneous localization of the density into "atoms" but in an
      amorphous structure having many of the structural characteristics of a glass. A
      small change of the protocol leads, at the same temperature, to the formation of
      crystals, this time with the fcc structure typical of bulk Lennard-Jones solids.
      The fcc crystals have lower free energy than the amorphous structures which in
      turn are more stable than the liquid droplets. It is demonstrated that as the
      temperature is raised, the free energy differences between the structures
      decrease until the solid clusters become less stable than the liquid droplets and
      spontaneously melt. The presence of energy barriers separating the various
      structures is therefore clearly demonstrated.

PMID- 30110789
TI  - Symmetry-broken coherent state in a ring of nonlocally coupled identical
      oscillators.
AB  - We report on a modulated coherent state in a ring of nonlocally coupled
      oscillators. Although the identical oscillators are all synchronized under the
      symmetric coupling, the phase configuration has an inhomogeneous structure. This
      symmetry-broken coherent state exists only for a nonlocal coupling with both
      attracting and repulsive interactions, depending on the distance between
      oscillators, and emerges via a continuous bifurcation from a uniformly coherent
      state. We analyze the existence and stability of the modulated coherent states on
      the basis of Ott-Antonsen equations for the local order parameter. Our
      theoretical results are verified using the numerical simulations.

PMID- 30110791
TI  - Path integral approach to heat in quantum thermodynamics.
AB  - We study the heat statistics of a quantum Brownian motion described by the
      Caldeira-Leggett model. By using the path integral approach, we introduce a
      concept of the quantum heat functional along every pair of Feynman paths. This
      approach has the advantage of improving our understanding about heat in quantum
      systems. First, we demonstrate the microscopic reversibility of the system by
      connecting the heat functional to the forward and time-reversed probabilities.
      Second, we analytically prove the quantum-classical correspondence of the heat
      functional and their statistics, which allows us to obtain better intuitions
      about the difference between classical and quantum heat.

PMID- 30110792
TI  - Physical interpretation of the canonical ensemble for long-range interacting
      systems in the absence of ensemble equivalence.
AB  - In systems with long-range interactions, since energy is a nonadditive quantity,
      ensemble inequivalence can arise: it is possible that different statistical
      ensembles lead to different equilibrium descriptions, even in the thermodynamic
      limit. The microcanonical ensemble should be considered the physically correct
      equilibrium distribution as long as the system is isolated. The canonical
      ensemble, on the other hand, can always be defined mathematically, but it is
      quite natural to wonder to which physical situations it does correspond. We show
      numerically and, in some cases, analytically that the equilibrium properties of a
      generalized Hamiltonian mean-field model in which ensemble inequivalence is
      present are correctly described by the canonical distribution in (at least) two
      different scenarios: (a) when the system is coupled via local interactions to a
      large reservoir (even if the reservoir shows, in turn, ensemble inequivalence),
      and (b) when the mean-field interaction between a small part of a system and the
      rest of it is weakened by some kind of screening.

PMID- 30110794
TI  - Assessing uncertainties in x-ray single-particle three-dimensional
      reconstruction.
AB  - Modern technology for producing extremely bright and coherent x-ray laser pulses
      provides the possibility to acquire a large number of diffraction patterns from
      individual biological nanoparticles, including proteins, viruses, and DNA. These
      two-dimensional diffraction patterns can be practically reconstructed and
      retrieved down to a resolution of a few angstroms. In principle, a sufficiently
      large collection of diffraction patterns will contain the required information
      for a full three-dimensional reconstruction of the biomolecule. The computational
      methodology for this reconstruction task is still under development and highly
      resolved reconstructions have not yet been produced. We analyze the expansion
      maximization-compression scheme, the current state of the art approach for this
      very challenging application, by isolating different sources of resolution
      limiting factors. Through numerical experiments on synthetic data we evaluate
      their respective impact. We reach conclusions of relevance for handling actual
      experimental data, and we also point out certain improvements to the underlying
      estimation algorithm. We also introduce a practically applicable computational
      methodology in the form of bootstrap procedures for assessing reconstruction
      uncertainty in the real data case. We evaluate the sharpness of this approach and
      argue that this type of procedure will be critical in the near future when
      handling the increasing amount of data.

PMID- 30110793
TI  - Control of Rayleigh-Taylor instability onset time and convective velocity by
      differential diffusion effects.
AB  - Fingering instabilities of a miscible interface between two fluids in a
      gravitational field can develop due to adverse density gradients as in the well
      known Rayleigh-Taylor (RT) and double-diffusive (DD) instabilities. In the
      absence of differential diffusion, the mixing rate and the onset time of the RT
      instability developing when a denser solution of a given solute A overlies a less
      dense solution of a solute B are respectively proportional and inversely
      proportional to the initial density difference Deltarho_{0} between the two
      superposed layers. We show here both experimentally and theoretically for porous
      media flows that when the mechanisms of RT and DD instabilities are combined, the
      properties of the convective growth of the fingers are controlled by the dynamic
      density jump Deltarho_{m} of the nonmonotonic density profile induced by the
      differential diffusion effects. In particular, the onset time and mixing rate can
      be controlled by varying the ratio of the diffusion coefficients of the solutes.

PMID- 30110795
TI  - Nonuniversality of front fluctuations for compact colonies of nonmotile bacteria.
AB  - The front of a compact bacterial colony growing on a Petri dish is a paradigmatic
      instance of non-equilibrium fluctuations in the celebrated Eden, or Kardar-Parisi
      Zhang (KPZ), universality class. While in many experiments the scaling exponents
      crucially differ from the expected KPZ values, the source of this disagreement
      has remained poorly understood. We have performed growth experiments with B.
      subtilis 168 and E. coli ATCC 25922 under conditions leading to compact colonies
      in the classically alleged Eden regime, where individual motility is suppressed.
      Non-KPZ scaling is indeed observed for all accessible times, KPZ asymptotics
      being ruled out for our experiments due to the monotonic increase of front
      branching with time. Simulations of an effective model suggest the occurrence of
      transient nonuniversal scaling due to diffusive morphological instabilities,
      agreeing with expectations from detailed models of the relevant biological
      reaction-diffusion processes.

PMID- 30110796
TI  - Anisotropy in electrical conductivity of films of aligned intersecting conducting
      rods.
AB  - Numerical simulations by means of the Monte Carlo method have been performed to
      study the electrical properties of a two-dimensional composite filled with
      rodlike particles. The main goal was to study the effect of the alignment of such
      rods on the anisotropy of its electrical conductivity. A continuous model was
      used. In this model, the rods have zero-width (i.e., infinite aspect ratio) and
      they may intersect each other. To involve both the low conductive host matrix and
      highly conductive fillers (rods) in the consideration, a discretization algorithm
      based on the use of a supporting mesh was applied. The discretization is
      equivalent to the substitution of rods with the polyominoes. Once discretized,
      the Frank-Lobb algorithm was applied to evaluate the electrical conductivity. Our
      main findings are (i) the alignment of the rods essentially affects the
      electrical conductivity and its anisotropy, (ii) the discrete nature of computer
      simulations is crucial. For slightly disordered system, high electrical
      anisotropy was observed at small filler content, suggesting a method to enable
      the production of optically transparent and highly anisotropic conducting films.

PMID- 30110797
TI  - Solution of the Noh problem with an arbitrary equation of state.
AB  - The classic self-similar solutions of the nonstationary compressible Euler
      equations obtained for a blast-wave propagation (Sedov, Taylor, and von Neumann),
      a shock-wave implosion (Guderley, Landau, and Stanyukovich), or an impulsive
      loading of a planar target (von Hoerner, Hafele, and Zel'dovich) have all been
      derived for a polytropic ideal gas. None of them can be generalized for a fluid
      with an arbitrary equation of state (EOS), such as the van der Waals EOS of a non
      ideal-gas or a three-term EOS of a condensed material. We demonstrate here that
      the Noh accretion-shock problem is an exception. Its self-similar solutions exist
      in cylindrical and spherical geometry for fluids and materials with an arbitrary
      EOS. Such solutions for finite accretion-shock strength and nonuniform inflow
      velocity are constructed semianalytically with a model three-term equation of
      state that includes cold, thermal ion (lattice), and thermal electron
      contributions to the pressure and internal energy. Examples are presented for
      aluminum and copper. Other material- and EOS-specific semianalytic solutions of
      the Noh problem can be easily constructed using the same method for any material
      that in the pressure range of interest can be approximated as a dissipation-free
      fluid with an arbitrary equation of state.

PMID- 30110798
TI  - Stiffness of probability distributions of work and Jarzynski relation for non
      Gibbsian initial states.
AB  - We consider closed quantum systems (into which baths may be integrated) that are
      driven, i.e., subject to time-dependent Hamiltonians. Our point of departure is
      the assumption that if systems start in non-Gibbsian states at some initial
      energies, the resulting probability distributions of work may be largely
      independent of the specific initial energies. It is demonstrated that this
      assumption has some far-reaching consequences, e.g., it implies the validity of
      the Jarzynski relation for a large class of non-Gibbsian initial states. By
      performing numerical analysis on integrable and nonintegrable spin systems, we
      find the above assumption fulfilled for all examples considered. Through an
      analysis based on Fermi's golden rule, we partially relate these findings to the
      applicability of the eigenstate thermalization ansatz to the respective driving
      operators.

PMID- 30110799
TI  - Multidimensional WKB approximation for particle tunneling.
AB  - In this paper we present a method for obtaining the WKB approximation for non
      separable multidimensional potentials. At its leading order one has to solve the
      classical Hamilton-Jacobi equation with zero energy for which a very efficient
      method is proposed. The essence of this method lies in the recognition that in
      the vicinity to the potential minimum the solution of Schrodinger equation has to
      approach that of coupled harmonic oscillators. Quantum corrections to the
      semiclassical result are then obtained very easily and to an arbitrarily high
      order. The method is applied to the calculation of the tunneling splitting and
      tunneling lifetime. We show that classical turning points are part of the
      dynamical problem; they could not be determined simply from looking at the form
      of the potential, but are obtained from the solution of the pertinent equations
      of motion.

PMID- 30110800
TI  - Growth probability and formation time of the individual Oosawa-Kasai protein
      fibril.
AB  - Protein fibrils are currently of great academic and practical interest because of
      their involvement in scores of severe human diseases and their promising use in
      various high-technology devices. The Oosawa-Kasai (OK) model of protein self
      assembly into fibrils has been widely used to gain mechanistic insight into the
      process of fibril formation and growth. Here this model is employed to obtain
      exact and mathematically simple expressions for the probability P_{n} of an
      individual fibril of n protein monomers to grow to a macroscopically large size
      and for the mean time tau_{n} that such a fibril needs for its formation. These
      expressions quantify the increase of P_{n} and the decrease of tau_{n} with
      increasing the concentration of monomeric protein in the solution. When used for
      analysis of experimental P_{n} and tau_{n} data, they make it possible to
      determine the parameters characterizing fibril nucleation and growth in the
      framework of the OK model. Finally, an expression is found for the mean time of
      the first appearance of an n-sized fibril in the protein solution. The results
      obtained are applicable to the formation of other aggregates corresponding to the
      OK fibrils, such as the one-dimensional Kossel-Stranski crystals and Ising
      ferromagnets.

PMID- 30110801
TI  - Behavior analysis of virtual-item gambling.
AB  - From the gambling logs of an online lottery game we extract the probability
      distribution of various quantities (e.g., bet value, total pool size, waiting
      time between successive gambles) as well as related correlation coefficients. We
      view the net change of income of each player as a random walk. The mean-squared
      displacement of these net income random walks exhibits a transition between a
      superdiffusive and a normal diffusive regime. We discuss different random-walk
      models with truncated power-law step lengths distributions that allow us to
      reproduce some of the properties extracted from the gambling logs. Analyzing the
      mean-squared displacement and the first-passage time distribution for these
      models allows us to identify the key features needed for observing this crossover
      from superdiffusion to normal diffusion.

PMID- 30110802
TI  - Fast Bayesian inference of the multivariate Ornstein-Uhlenbeck process.
AB  - The multivariate Ornstein-Uhlenbeck process is used in many branches of science
      and engineering to describe the regression of a system to its stationary mean.
      Here we present an O(N) Bayesian method to estimate the drift and diffusion
      matrices of the process from N discrete observations of a sample path. We use
      exact likelihoods, expressed in terms of four sufficient statistic matrices, to
      derive explicit maximum a posteriori parameter estimates and their standard
      errors. We apply the method to the Brownian harmonic oscillator, a bivariate
      Ornstein-Uhlenbeck process, to jointly estimate its mass, damping, and stiffness
      and to provide Bayesian estimates of the correlation functions and power spectral
      densities. We present a Bayesian model comparison procedure, embodying Ockham's
      razor, to guide a data-driven choice between the Kramers and Smoluchowski limits
      of the oscillator. These provide novel methods of analyzing the inertial motion
      of colloidal particles in optical traps.

PMID- 30110803
TI  - Nonequilibrium transient phenomena in the washboard potential.
AB  - Transient properties of the one-dimensional washboard potential are investigated
      in order to understand observed modulations in the statistics of escape events.
      Specifically, we analyze the effects of different kinds of initial conditions on
      the escape distribution obtained by linearly increasing the tilt of the
      potential. Despite the complexity of the dynamics leading up to the eventual
      escape, we find that the overall statistics can be interpreted in terms of the
      system parameters, which offers illuminating perspectives for driven one
      dimensional systems with washboard potentials. We choose parameters sets relevant
      for Josephson junctions, a commonly studied system due to both its applications
      and its use as a model system in condensed matter physics.

PMID- 30110804
TI  - Decomposition of the entropy production rate and nonequilibrium thermodynamics of
      switching diffusion processes.
AB  - A switching diffusion process (SDP) is a widely used stochastic model in physics
      and biology, especially for molecular motors that exhibit a discrete internal
      chemical kinetics as well as a continuous external mechanical motion. The
      nonequilibrium thermodynamics of switching diffusion processes has not been
      extensively studied yet. In the present paper, we propose the decomposition of
      the entropy production rate in one-dimensional SDPs, based on the flux
      decomposition. However, similar decompositions of the housekeeping heat
      dissipation rate and free energy dissipation rate cannot guarantee the non
      negativity of each decomposed component. Hence, we modify this decomposition with
      the flow of exponential relative information under steady-state fluxes, resulting
      in another decomposition with all non-negative components. Furthermore, we also
      provide the nonequilibrium thermodynamics of one-dimensional SDPs under the
      perspectives of coarse -graining and exchange of information between the chemical
      kinetics and mechanical motion, resulting in several other decompositions of
      entropy production rate. Finally, we generalize all the results to high
      dimensional SDPs with a more general mathematical treatment.

PMID- 30110805
TI  - Estimating the outcome of spreading processes on networks with incomplete
      information: A dimensionality reduction approach.
AB  - Recent advances in data collection have facilitated the access to time-resolved
      human proximity data that can conveniently be represented as temporal networks of
      contacts between individuals. While the structural and dynamical information
      revealed by this type of data is fundamental to investigate how information or
      diseases propagate in a population, data often suffer from incompleteness, which
      possibly leads to biased estimations in data-driven models. A major challenge is
      thus to estimate the outcome of spreading processes occurring on temporal
      networks built from partial information. To cope with this problem, we devise an
      approach based on non-negative tensor factorization, a dimensionality reduction
      technique from multilinear algebra. The key idea is to learn a low-dimensional
      representation of the temporal network built from partial information and to use
      it to construct a surrogate network similar to the complete original network. To
      test our method, we consider several human-proximity networks, on which we
      perform resampling experiments to simulate a loss of data. Using our approach on
      the resulting partial networks, we build a surrogate version of the complete
      network for each. We then compare the outcome of a spreading process on the
      complete networks (nonaltered by a loss of data) and on the surrogate networks.
      We observe that the epidemic sizes obtained using the surrogate networks are in
      good agreement with those measured on the complete networks. Finally, we propose
      an extension of our framework that can leverage additional data, when available,
      to improve the surrogate network when the data loss is particularly large.

PMID- 30110806
TI  - Phase diagrams and crystal-fluid surface tensions in additive and nonadditive two
      dimensional binary hard-disk mixtures.
AB  - Using density functionals from fundamental measure theory, phase diagrams and
      crystal-fluid surface tensions in additive and nonadditive (Asakura-Oosawa model)
      two-dimensional binary hard-disk mixtures are determined for the whole range of
      size ratios q=smalldiameter/largediameter, assuming random disorder (lattice
      points or interstitial occupied by large or small disks at random) in the crystal
      phase. The fluid-crystal transitions are first order due to the assumption of a
      periodic unit cell in the density-functional calculations. Qualitatively, the
      shape of the phase diagrams is similar to the case of three-dimensional hard
      sphere mixtures. For the nonadditive case, a broadening of the fluid-crystal
      coexistence region is found for small q, whereas for large q a vapor-fluid
      transition intervenes. In the additive case, we find a sequence of spindle-type,
      azeotropic, and eutectic phase diagrams upon lowering q from 1 to 0.6. The
      transition from azeotropic to eutectic is different from the three-dimensional
      case. Surface tensions in general become smaller (up to a factor 2) upon addition
      of a second species and they are rather small. The minimization of the
      functionals proceeds without restrictions and optimized graphics card routines
      are used.

PMID- 30110807
TI  - Active bundles of polar and bipolar filaments.
AB  - Bundles of actin filaments and molecular motors of the myosin family are a common
      subcellular organizational motif. Typically, such bundles are under contractile
      stress resulting from interactions between the filaments and the motors. This
      holds in particular for contractile rings that appear in the late stages of cell
      division in animal cells and that cleave the mother into two daughter cells. It
      was recently shown that myosin organizes into regularly spaced clusters along
      rings in mammalian cells, whereas myosin clusters in fission yeast travel along
      the perimeter of actomyosin rings [Wollrab et al., Nat. Commun. 7, 11860
      (2016)2041-172310.1038/ncomms11860]. A mechanism based on the association of the
      structurally polar actin filaments into bipolar structures was shown to provide a
      common explanation for both observations. Here, we analyze the dynamics of this
      mechanism in detail. We find a rich phase diagram depending on the actomyosin
      interaction strength and the stability of the bipolar structures. The system can
      notably organize into traveling waves. Furthermore, we identify the nature of the
      bifurcations connecting the various patterns as parameters are changed. Finally,
      we report experimental patterns observed in cytokinetic rings in fission yeast
      and link them to solutions of our dynamic equations. Our analysis highlights the
      possible role played by local polarity sorting of actin filaments for the
      dynamics and functionality of actomyosin networks.

PMID- 30110808
TI  - Characterizing information-theoretic storage and transfer in continuous time
      processes.
AB  - The characterization of information processing is an important task in complex
      systems science. Information dynamics is a quantitative methodology for modeling
      the intrinsic information processing conducted by a process represented as a time
      series, but to date has only been formulated in discrete time. Building on
      previous work which demonstrated how to formulate transfer entropy in continuous
      time, we give a total account of information processing in this setting,
      incorporating information storage. We find that a convergent rate of predictive
      capacity, comprising the transfer entropy and active information storage, does
      not exist, arising through divergent rates of active information storage. We
      identify that active information storage can be decomposed into two separate
      quantities that characterize predictive capacity stored in a process: active
      memory utilization and instantaneous predictive capacity. The latter involves
      prediction related to path regularity and so solely inherits the divergent
      properties of the active information storage, while the former permits
      definitions of pathwise and rate quantities. We formulate measures of memory
      utilization for jump and neural spiking processes and illustrate measures of
      information processing in synthetic neural spiking models and coupled Ornstein
      Uhlenbeck models. The application to synthetic neural spiking models demonstrates
      that active memory utilization for point processes consists of discontinuous jump
      contributions (at spikes) interrupting a continuously varying contribution
      (relating to waiting times between spikes), complementing the behavior previously
      demonstrated for transfer entropy in these processes.

PMID- 30110809
TI  - Buckling of a rod penetrating into granular media.
AB  - We investigate experimentally the possible buckling of a thin rod when
      penetrating downwards into a granular packing. When its bottom end reaches a
      specific depth, the rod may start buckling provided that the embrace is not
      enough to stop that phenomenon. The critical rod depth z_{c} at buckling is
      observed to scale with the rod length L either as 1/L or 1/L^{2}. These two
      scalings are shown to arise from the two resistant force terms that come into
      play during the rod penetration: a pressure force at the bottom of the rod that
      increases linearly with depth and a frictional force on the rod side that
      increases quadratically with depth. At the buckling point, the destabilizing
      force corresponds to the expected value given from conventional Euler's critical
      load for a rod bottom end considered as fixed in the granular clutch. Finally, we
      draw a buckling-nonbuckling phase diagram in a parameter space given by the rod
      aspect ratio and a rod-to-grain stress ratio.

PMID- 30110811
TI  - Discontinuous shear thickening in Brownian suspensions.
AB  - Discontinuous shear thickening in dense suspensions naturally emerges from the
      activation of frictional forces by shear flow in non-Brownian systems close to
      jamming. Yet, this physical picture is incomplete as most experiments study soft
      colloidal particles subject to thermal fluctuations. To characterize
      discontinuous shear thickening in colloidal suspensions, we use computer
      simulations to provide a complete description of the competition between athermal
      jamming, frictional forces, thermal motion, particle softness, and shear flow. We
      intentionally neglect hydrodynamics, electrostatics, lubrication, and inertia,
      but can nevertheless achieve quantitative agreement with experimental findings.
      In particular, shear thickening corresponds to a crossover between frictionless
      and frictional jamming regimes which is controlled by thermal fluctuations and
      particle softness and occurs at a softness dependent Peclet number. We also
      explore the consequences of our findings for constant pressure experiments, and
      critically discuss the reported emergence of "S-shaped" flow curves. Our work
      provides the minimal ingredients to quantitatively interpret a large body of
      experimental work on discontinuous shear thickening in colloidal suspensions.

PMID- 30110810
TI  - Nonlinear drag forces and the thermostatistics of overdamped motion.
AB  - Diverse processes in statistical physics are usually analyzed on the assumption
      that the drag force acting on a test particle moving in a resisting medium is
      linear on the velocity of the particle. However, nonlinear drag forces do appear
      in relevant situations that are currently the focus of experimental and
      theoretical work. Motivated by these developments, we explore the consequences of
      nonlinear drag forces for the thermostatistics of systems of interacting
      particles performing overdamped motion. We derive a family of nonlinear Fokker
      Planck equations for these systems, taking into account the effects of nonlinear
      drag forces. We investigate the main properties of these evolution equations,
      including an H-theorem, and obtain exact solutions of the stretched q-exponential
      form.

PMID- 30110812
TI  - Quantifying reconnective activity in braided vector fields.
AB  - We introduce a technique for evaluating the changing connectivity of a vector
      field whose integral curves (field lines) form tangled tubular bundles.
      Applications of such fields include magnetic flux ropes, relativistic plasma
      jets, stirred two-dimensional fluids, superfluid vortices, and polymer networks.
      The technique is based on maps of the field line winding-the average entanglement
      of a given field line with all other field lines. Previously this had been
      developed for divergence-free vector fields. By extending some previous
      theoretical results, we show how it can be applied to any vector field that forms
      a tubular bundle. We demonstrate the efficacy of this technique on data from
      laboratory plasma experiments with two interacting magnetic flux ropes. Performed
      in the UCLA Large Plasma Device, the plasma's magnetic field structure is too
      complex to identify a single dominant current sheet as an expected site of
      magnetic reconnection. Previously, this complex structure had restricted the
      ability to analyze the evolving magnetic connectivity, but this is no such
      restriction to our method. We demonstrate that the plasma establishes a
      periodically oscillating cycle of magnetic field structure variation which, while
      triggered by an ideal instability, is dominated by magnetic reconnection. This
      reconnection leads to periodically varying coherence of a merged central flux
      rope, a conclusion supported by analysis of the writhing structure of the
      magnetic field.

PMID- 30110813
TI  - Magnetohydrodynamics- and magnetosolutal-transport-mediated evaporation dynamics
      in paramagnetic pendant droplets under field stimulus.
AB  - Evaporation kinetics of pendant droplets is an area of immense importance in
      several applications, in addition to possessing rich fluid dynamics and thermal
      transport physics. This article experimentally and analytically sheds insight
      into the augmented evaporation dynamics of paramagnetic pendant droplets in the
      presence of a magnetic field stimulus. The literature provides information that
      solutal advection and the solutal Marangoni effect lead to enhanced evaporation
      in droplets with solvated ions. The main focus of this article is to modulate the
      thermosolutal advection with the aid of an external magnetic field and comprehend
      the dynamics of the evaporation process under such complex multiphysics
      interactions. Experimental observations reveal that the evaporation rate enhances
      as a direct function of the magnetic moment of the solvated magnetic element
      ions, thereby pointing at the magnetophoretic and magnetosolutal advection.
      Additionally, flow visualization by particle image velocimetry illustrates that
      the internal advection currents within the droplet increase in magnitude and are
      distorted in orientation by the magnetic field. A mathematical formalism based on
      magnetothermal and magnetosolutal advection has been proposed via scaling
      analysis of the species and energy conservation equations. The formalism takes
      into account all major governing factors, viz., the magnetothermal and
      magnetosolutal Marangoni numbers, magneto-Prandtl and magneto-Schmidt numbers,
      and the Hartmann number. The modeling establishes the magnetosolutal advection to
      be the dominant factor behind the augmented evaporation dynamics. Accurate
      validation of the experimental internal circulation velocity is obtained from the
      proposed model. This study reveals rich insight into the magnetothermosolutal
      hydrodynamics in paramagnetic droplets.

PMID- 30110814
TI  - Phase transitions, order by disorder, and finite entropy in the Ising
      antiferromagnetic bilayer honeycomb lattice.
AB  - We present an analytical and numerical study of the Ising model on a bilayer
      honeycomb lattice including interlayer frustration and coupling with an external
      magnetic field. First, we discuss the exact T=0 phase diagram, where we find
      finite entropy phases for different magnetizations. Then, we study the magnetic
      properties of the system at finite temperature using complementary analytical
      techniques (Bethe lattice) and two types of Monte Carlo algorithms (Metropolis
      and Wang-Landau). We characterize the phase transitions and discuss the phase
      diagrams. The system presents a rich phenomenology: There are first- and second
      order transitions, low-temperature phases with extensive degeneracy, and order-by
      disorder state selection.

PMID- 30110815
TI  - Family-size variability grows with collapse rate in a birth-death-catastrophe
      model.
AB  - Forest-fire and avalanche models support the notion that frequent catastrophes
      prevent the growth of very large populations and as such, prevent rare large
      scale catastrophes. We show that this notion is not universal. A new model class
      leads to a paradigm shift in the influence of catastrophes on the family-size
      distribution of subpopulations. We study a simple population dynamics model where
      individuals, as well as a whole family, may die with a constant probability,
      accompanied by a logistic population growth model. We compute the characteristics
      of the family-size distribution in steady state and the phase diagram of the
      steady-state distribution and show that the family and catastrophe size variances
      increase with the catastrophe frequency, which is the opposite of common
      intuition. Frequent catastrophes are balanced by a larger net-growth rate in
      surviving families, leading to the exponential growth of these families. When the
      catastrophe rate is further increased, a second phase transition to extinction
      occurs when the rate of new family creations is lower than their destruction rate
      by catastrophes.

PMID- 30110816
TI  - Nonlinear multimode buckling dynamics examined with semiflexible paramagnetic
      filaments.
AB  - We present the contractile buckling dynamics of superparamagnetic filaments using
      experimental, theoretical, and simulation approaches. Under the influence of an
      orthogonal magnetic field, flexible magnetic filaments exhibit higher-order
      buckling dynamics that can be identified as occurring in three stages:
      initiation, development, and decay. Unlike initiation and decay stages where the
      balance between magnetic interactions and elastic forces is dominant, in the
      development stage, the influence of hydrodynamic drag results in transient
      buckling dynamics that is nonlinear along the filament contour. The inhomogeneous
      temporal evolution of the buckling wavelength is analyzed and the contractions
      under various conditions are compared.

PMID- 30110817
TI  - Steady oscillations in aggregation-fragmentation processes.
AB  - We report surprising steady oscillations in aggregation-fragmentation processes.
      Oscillating solutions are observed for the class of aggregation kernels
      K_{i,j}=i^{nu}j^{MU}+j^{nu}i^{MU} homogeneous in masses i and j of merging
      clusters and fragmentation kernels, F_{ij}=lambdaK_{ij}, with parameter lambda
      quantifying the intensity of the disruptive impacts. We assume a complete
      decomposition (shattering) of colliding partners into monomers. We show that an
      assumption of a steady-state distribution of cluster sizes, compatible with
      governing equations, yields a power law with an exponential cutoff. This
      prediction agrees with simulation results when theta=nu-MU<1. For theta=nu-MU>1,
      however, the densities exhibit an oscillatory behavior. While these oscillations
      decay for not very small lambda, they become steady if theta is close to 2 and
      lambda is very small. Simulation results lead to a conjecture that for theta<1
      the system has a stable fixed point, corresponding to the steady-state density
      distribution, while for any theta>1 there exists a critical value lambda_{c},
      such that for lambda<lambda_{c}, the system has an attracting limit cycle. This
      is rather striking for a closed system of Smoluchowski-like equations, lacking
      any sinks and sources of mass.

PMID- 30110819
TI  - Flow characteristics of Chlamydomonas result in purely hydrodynamic scattering.
AB  - It has long been believed that eukaryotic flagellated swimming cells feel solid
      boundaries through direct ciliary contact. Specifically, based on observations of
      behavior of green alga Chlamydomonas reinhardtii it has been reported that it is
      their "flagella [that] prevent the cell body from touching the surface" [Kantsler
      et al., Proc. Natl. Acad. Sci. USA 110, 1187 (2013)PNASA60027
      842410.1073/pnas.1210548110]. Here, via investigation of a model swimmer whose
      flow field closely resembles that of C. reinhardtii, we show that the scattering
      from a wall can be purely hydrodynamic and that no mechanical or flagellar force
      is needed for sensing and escaping the boundary.

PMID- 30110818
TI  - Inferring power-grid topology in the face of uncertainties.
AB  - We develop methods to efficiently reconstruct the topology and line parameters of
      a power grid from the measurement of nodal variables. We propose two compressed
      sensing algorithms that minimize the amount of necessary measurement resources by
      exploiting network sparsity, symmetry of connections, and potential prior
      knowledge about the connectivity. The algorithms are reciprocal to established
      state estimation methods, where nodal variables are estimated from few
      measurements given the network structure. Hence, they enable an advanced grid
      monitoring where both state and structure of a grid are subject to uncertainties
      or missing information.

PMID- 30110820
TI  - Violent relaxation in quantum fluids with long-range interactions.
AB  - Violent relaxation is a process that occurs in systems with long-range
      interactions. It has the peculiar feature of dramatically amplifying small
      perturbations, and rather than driving the system to equilibrium, it instead
      leads to slowly evolving configurations known as quasistationary states that fall
      outside the standard paradigm of statistical mechanics. Violent relaxation was
      originally identified in gravity-driven stellar dynamics; here, we extend the
      theory into the quantum regime by developing a quantum version of the Hamiltonian
      mean field (HMF) model which exemplifies many of the generic properties of long
      range interacting systems. The HMF model can either be viewed as describing
      particles interacting via a cosine potential, or equivalently as the kinetic XY
      model with infinite-range interactions, and its quantum fluid dynamics can be
      obtained from a generalized Gross-Pitaevskii equation. We show that singular
      caustics that form during violent relaxation are regulated by interference
      effects in a universal way described by Thom's catastrophe theory applied to
      waves and this leads to emergent length scales and timescales not present in the
      classical problem. In the deep quantum regime we find that violent relaxation is
      suppressed altogether by quantum zero-point motion. Our results are relevant to
      laboratory studies of self-organization in cold atomic gases with long-range
      interactions.

PMID- 30110821
TI  - Missing-level statistics and analysis of the power spectrum of level fluctuations
      of three-dimensional chaotic microwave cavities.
AB  - We present an experimental study of missing-level statistics of three-dimensional
      chaotic microwave cavities. The investigation is reinforced by the power spectrum
      of level fluctuations analysis, which also takes into account the missing levels.
      On the basis of our data sets we demonstrate that the power spectrum of level
      fluctuations in combination with short- and long-range spectral fluctuations
      provides a powerful tool for the determination of the fraction of randomly
      missing levels in systems that display wave chaos such as the three-dimensional
      chaotic microwave cavities. The experimental results are in good agreement with
      the analytical expressions that explicitly take into account the fraction of
      observed levels phi. We also show that in the case of incomplete spectra with
      many unresolved states the above procedures may fail. In such a case the random
      matrix theory calculations can be useful for the determination of missing levels.

PMID- 30110822
TI  - Street map analysis with excitable chemical medium.
AB  - Belousov-Zhabotinsky (BZ) thin layer solution is a fruitful substrate for
      designing unconventional computing devices. A range of logical circuits, wet
      electronic devices, and neuromorphic prototypes have been constructed.
      Information processing in BZ computing devices is based on interaction of
      oxidation (excitation) wave fronts. Dynamics of the wave fronts propagation is
      programed by geometrical constraints and interaction of colliding wave fronts is
      tuned by illumination. We apply the principles of BZ computing to explore a
      geometry of street networks. We use two-variable Oregonator equations, the most
      widely accepted and verified in laboratory experiments BZ models, to study
      propagation of excitation wave fronts for a range of excitability parameters,
      with gradual transition from excitable to subexcitable to nonexcitable. We
      demonstrate a pruning strategy adopted by the medium with decreasing excitability
      when wider and ballistically appropriate streets are selected. We explain
      mechanics of streets selection and pruning. The results of the paper will be used
      in future studies of studying dynamics of cities and characterizing geometry of
      street networks.

PMID- 30110823
TI  - Statistics of vector Manakov rogue waves.
AB  - We present a statistical analysis based on the height and return-time
      probabilities of high-amplitude wave events in both focusing and defocusing
      Manakov systems. We find that analytical rational or semirational solutions,
      associated with extreme, rogue wave (RW) structures, are the leading high
      amplitude events in this system. We define the thresholds for classifying an
      extreme wave event as a RW. Our results indicate that there is a strong
      relationship between the type of RW and the mechanism which is responsible for
      its creation. Initially, high-amplitude events originate from modulation
      instability. Upon subsequent evolution, the interaction among these events
      prevails as the mechanism for RW creation. We suggest a strategy for confirming
      the basic properties of different extreme events. This involves the definition of
      proper statistical measures at each stage of the RW dynamics. Our results point
      to the need for redefining criteria for identifying RW events.

PMID- 30110824
TI  - Twist-induced crossover from two-dimensional to three-dimensional turbulence in
      active nematics.
AB  - While studies of active nematics in two dimensions have shed light on various
      aspects of the flow regimes and topology of active matter, three-dimensional
      properties of topological defects and chaotic flows remain unexplored. By
      confining a film of active nematics between two parallel plates, we use continuum
      simulations and analytical arguments to demonstrate that the crossover from quasi
      two-dimensional (quasi-2D) to three-dimensional (3D) chaotic flows is controlled
      by the morphology of the disclination lines. For small plate separations, the
      active nematic behaves as a quasi-2D material, with straight topological
      disclination lines spanning the height of the channel and exhibiting effectively
      2D active turbulence. Upon increasing channel height, we find a crossover to 3D
      chaotic flows due to the contortion of disclinations above a critical activity.
      Above this critical activity highly contorted disclination lines and disclination
      loops are formed. We further show that these contortions are engendered by twist
      perturbations producing a sharp change in the curvature of disclinations.

PMID- 30110825
TI  - Assessing the accuracy of three classical density functional theories of the
      electrical double layer.
AB  - Classical density functional theory (DFT) is a useful tool to compute the
      structure of the electrical double layer because it includes ion-ion correlations
      due to excluded-volume effects (i.e., steric correlations) and ion screening
      effects (i.e., electrostatic correlations beyond the electrostatic mean-field
      potential). This paper systematically analyzes the accuracies of three different
      electrostatic excess free-energy functionals, as compared to Monte Carlo (MC)
      simulations of the planar electrical double layer, over a large parameter space.
      Specifically, we tested the reference fluid density (RFD) [Gillespie et al., J.
      Phys.: Condens. Matter 14, 12129 (2002)10.1088/0953-8984/14/46/317],
      functionalized mean spherical approximation (fMSA) [Roth and Gillespie, J. Phys.:
      Condens. Matter 28, 244006 (2016)10.1088/0953-8984/28/24/244006], and bulk fluid
      (BF) [Kierlik and Rosinberg, Phys. Rev. A 44, 5025
      (1991)10.1103/PhysRevA.44.5025; Y. Rosenfeld, J. Chem. Phys. 98, 8126
      (1993)10.1063/1.464569] functionals. Previous work compared these DFT methods to
      MC simulations only for a small set of parameters. Here, a total of twelve
      different cations were studied, with valences of +1, +2, and +3 and ion diameters
      of 0.15, 0.30, 0.60, and 0.90 nm at bulk concentrations between 1 MUM and 1 M.
      The anion always had valence -1 and diameter 0.30 nm. The structure of the double
      layer of these charged, hard-sphere ions was computed for surface charges ranging
      from 0 to -0.50C/m^{2}. All the DFTs were compared against each other for all the
      parameters, as well as to 378 MC simulations. Overall, RFD was the best of the
      three functionals, while BF was the least accurate. fMSA performed significantly
      better than BF, making it a reasonable choice that is less computationally
      expensive than RFD. For monovalent cations, all three functionals worked
      reasonably well, except BF was qualitatively different from MC at very low
      surface charges. For multivalent cations, BF underestimated charge inversion
      while fMSA overestimated it. All DFTs performed poorly for small multivalent
      ions.

PMID- 30110826
TI  - Anisotropy in electrical conductivity of two-dimensional films containing aligned
      nonintersecting rodlike particles: Continuous and lattice models.
AB  - The electrical conductivity of two-dimensional films filled with rodlike
      particles (rods) was simulated by the Monte Carlo method. The main attention has
      been paid to the investigation of the effect of the rod alignment on the
      electrical properties of the films. Both continuous and lattice approaches were
      used. Intersections of particles were forbidden. Our main findings are (i) both
      models demonstrate similar behaviors, (ii) at low concentration of rods, both
      approaches lead to the same dependencies of the electrical conductivity on the
      concentration of the rods, (iii) the alignment of the rods essentially affects
      the electrical conductivity, (iv) at some concentrations of partially aligned
      rods, the films may be conducting only in one direction, and (v) the films may
      simultaneously be both highly transparent and electrically anisotropic.

PMID- 30110827
TI  - Quantum work for sudden quenches in Gaussian random Hamiltonians.
AB  - In the context of nonequilibrium quantum thermodynamics, variables like work
      behave stochastically. A particular definition of the work probability density
      function (pdf) for coherent quantum processes allows the verification of the
      quantum version of the celebrated fluctuation theorems, due to Jarzynski and
      Crooks, that apply when the system is driven away from an initial equilibrium
      thermal state. Such a particular pdf depends basically on the details of the
      initial and final Hamiltonians, on the temperature of the initial thermal state,
      and on how some external parameter is changed during the coherent process. Using
      random matrix theory we derive a simple analytic expression that describes the
      general behavior of the work characteristic function G(u), associated with this
      particular work pdf for sudden quenches, valid for all the traditional Gaussian
      ensembles of Hamiltonians matrices. This formula well describes the general
      behavior of G(u) calculated from single draws of the initial and final
      Hamiltonians in all ranges of temperatures.

PMID- 30110828
TI  - Interactions between a fluctuating polymer barrier and transport factors together
      with enzyme action are sufficient for selective and rapid transport through the
      nuclear pore complex.
AB  - The nuclear pore complex, the only pathway for transport between the nucleus and
      cytoplasm, functions as a highly selective gate that blocks nonspecific
      macromolecules while allowing the rapid transport of tagged [transport factor
      (TF) bound] cargo up to an order of magnitude larger. The mechanism of this
      gate's operation is not yet fully understood and progress has been primarily
      hindered by the inherent complexity and multiscale nature of the problem. One
      needs to consider the hundreds of disordered proteins (phenylalanine glycine
      nucleoporins or FG nups) lining the pore, as well as their overall architecture
      and dynamics at the microsecond scale, while also accounting for transport at the
      millisecond scale across the entire pore. Here we formulate an approach that
      addresses transport properties over a large range of length and time scales. We
      do this by incorporating microscopic biophysical details, such as charge and
      specific TF-FG nup interactions, to compute the free energy landscape encountered
      by the cargo. We connect this to macroscopic transport by treating cargo
      translocation as a stochastic barrier crossing process and computing the current
      and the translocation time. We then identify distinct transport regimes (fast
      permeable, slow permeable, and impermeable) determined by the cargo size, TF
      affinity for FG nups, and the activity of the enzymes that cleave TFs from cargo.
      Our results, therefore provide an integrated picture of transport through the
      NPC, while highlighting how FG nup interactions with TFs and enzyme activity
      cooperate to produce selectivity and efficiency.

PMID- 30110830
TI  - Anomalous dynamics of the endoplasmic reticulum network.
AB  - Large portions of the endoplasmic reticulum (ER) in eukaryotic cells are
      organized as dynamic networks whose segments are connected by three-way
      junctions. Here we show that ER junctions move subdiffusively with signatures of
      fractional Brownian motion and a strong dependence on the cytoskeleton's
      integrity: The time-averaged mean square displacement scales as
      <r^{2}(tau)>_{t}~tau^{alpha} with alpha~0.5 in untreated cells and alpha~0.3 when
      disrupting microtubules, with successive steps being anticorrelated in both
      cases. We explain our observations by considering ER junctions to move like
      monomers in (semi)flexible polymer segments immersed in a viscoelastic
      environment. We also report that ER networks have a nontrivial fractal dimension
      d_{f}~1.6 on mesoscopic scales and we provide evidence that the organelle's
      dynamics is governed by fractons.

PMID- 30110831
TI  - Fast inverse nonlinear Fourier transform.
AB  - This paper considers the non-Hermitian Zakharov-Shabat scattering problem which
      forms the basis for defining the SU(2)-nonlinear Fourier transform (NFT). The
      theoretical underpinnings of this generalization of the conventional Fourier
      transform is quite well established in the Ablowitz-Kaup-Newell-Segur formalism;
      however, efficient numerical algorithms that could be employed in practical
      applications are still unavailable. In this paper, we present two fast inverse
      NFT algorithms with O(KN+Nlog^{2}N) complexity and a convergence rate of O(N^{
      2}), where N is the number of samples of the signal and K is the number of
      eigenvalues. These algorithms are realized using a new fast layer-peeling (LP)
      scheme [O(Nlog^{2}N)] together with a new fast Darboux transformation (FDT)
      algorithm [O(KN+Nlog^{2}N)] previously developed by V. Vaibhav [Phys. Rev. E 96,
      063302 (2017)2470-004510.1103/PhysRevE.96.063302]. The proposed fast inverse NFT
      algorithm proceeds in two steps: The first step involves computing the radiative
      part of the potential using the fast LP scheme for which the input is synthesized
      under the assumption that the radiative potential is nonlinearly bandlimited,
      i.e., the continuous spectrum has a compact support. The second step involves
      addition of bound states using the FDT algorithm. Finally, the performance of
      these algorithms is demonstrated through exhaustive numerical tests.

PMID- 30110829
TI  - Golden aspect ratio for ion transport simulation in nanopores.
AB  - Access resistance indicates how well current carriers from a bulk medium can
      converge to a pore or opening and is an important concept in nanofluidic devices
      and in cell physiology. In simplified scenarios, when the bulk dimensions are
      infinite in all directions, it depends only on the resistivity and pore radius.
      These conditions are not valid in all-atom molecular dynamics simulations of
      transport, due to the computational cost of large simulation cells, and can even
      break down in micro- and nanoscale systems due to strong confinement. Here, we
      examine a scaling theory for the access resistance that predicts a special
      simulation cell aspect ratio-the golden aspect ratio-where finite-size effects
      are eliminated. Using both continuum and all-atom simulations, we demonstrate
      that this golden aspect ratio exists and that it takes on a universal value in
      linear response and moderate concentrations. Outside of linear response, it gains
      an apparent dependence on characteristics of the transport scenario
      (concentration, voltages, etc.) for small simulation cells, but this dependence
      vanishes at larger length scales. These results will enable the use of all-atom
      molecular dynamics simulations to study contextual properties of access
      resistance-its dependence on protein and molecular-scale fluctuations, the
      presence of charges, and other functional groups-and yield the opportunity to
      quantitatively compare computed and measured resistances.

PMID- 30110832
TI  - Geometrical percolation threshold of congruent cuboidlike particles in
      overlapping particle systems.
AB  - With the advances in artificial particle synthesis, it is possible to create
      particles with unique shapes. Particle shape becomes a feasible parameter for
      tuning the percolation behavior. How to accurately predict the percolation
      threshold by particle characteristics for arbitrary particles has aroused great
      interest. Towards this end, a versatile family of cuboidlike particles and a
      numerical contact detection algorithm for these particles are presented here.
      Then, combining with percolation theory, the continuum percolation of randomly
      distributed overlapping cuboidlike particles is studied. The global percolation
      threshold phi_{c} of overlapping particles with broad ranges of the shape
      parameter m in [1.0,+infinity) and aspect ratio a/b in [0.1, 10.0] is computed
      via a finite-size scaling technique. Using the generalized excluded-volume
      approximation, an analytical formula is proposed to quantify the dependence of
      phi_{c} on the parameters m and a/b, and its reliability is verified. The results
      reveal that the percolation threshold phi_{c} of overlapping cuboidlike particles
      is heavily dependent on the shapes of particles, and much more sensitive to a/b
      than m. As the cuboidlike particles become spherical (i.e., m=1.0 and a/b=1.0),
      the maximum threshold phi_{c,max} can be obtained.

PMID- 30110834
TI  - Bound on the exponential growth rate of out-of-time-ordered correlators.
AB  - It has been conjectured by Maldacena, Shenker, and Stanford [J. Maldacena, S. H.
      Shenker, and D. Stanford, J. High Energy Phys. 08 (2016)
      10610.1007/JHEP08(2016)106] that the exponential growth rate of the out-of-time
      ordered correlator (OTOC) F(t) has a universal upper bound 2pik_{B}T/h. Here we
      introduce a one-parameter family of out-of-time-ordered correlators F_{gamma}(t)
      (0<=gamma<=1), which has as good properties as F(t) as a regularization of the
      out-of-time-ordered part of the squared commutator <[A[over ](t),B[over
      ](0)]^{2}> that diagnoses quantum many-body chaos, and coincides with F(t) at
      gamma=1/2. We rigorously prove that if F_{gamma}(t) shows a transient exponential
      growth for all gamma in 0<=gamma<=1, that is, if the OTOC shows an exponential
      growth regardless of the choice of the regularization, then the growth rate
      lambda does not depend on the regularization parameter gamma and satisfies the
      inequality lambda<=2pik_{B}T/h.

PMID- 30110833
TI  - Activated dynamics: An intermediate model between the random energy model and the
      p-spin model.
AB  - To study the activated dynamics of mean-field glasses, which takes place on times
      of order exp(N), where N is the system size, we introduce a new model, the
      correlated random energy model (CREM), that allows for a smooth interpolation
      between the REM and the p-spin models. We study numerically and analytically the
      CREM in the intermediate regime between REM and p-spin. We fully characterize its
      energy landscape, which is like a golf course but, at variance with the REM, has
      metabasins (or holes) containing several configurations. We find that an
      effective description for the dynamics, in terms of traps, emerges, provided that
      one identifies metabasins in the CREM with configurations in the trap model.

PMID- 30110835
TI  - Density classification performance and ergodicity of the Gacs-Kurdyumov-Levin
      cellular automaton model IV.
AB  - Almost four decades ago, Gacs, Kurdyumov, and Levin introduced three different
      cellular automata to investigate whether one-dimensional nonequilibrium
      interacting particle systems are capable of displaying phase transitions, and, as
      a byproduct, they introduced the density classification problem (the ability to
      classify arrays of symbols according to their initial density) in the cellular
      automata literature. Their model II became a well-known model in theoretical
      computer science and statistical mechanics. The other two models, however, did
      not receive much attention. Here we characterize the density classification
      performance of Gacs, Kurdyumov, and Levin's model IV, a four-state cellular
      automaton with three absorbing states-only two of which are attractive-by
      numerical simulations. We show that model IV compares well with its sibling model
      II in the density classification task: the additional states slow down the
      convergence to the majority state but confer a slight advantage in classification
      performance. We also show that, unexpectedly, initial states diluted in one of
      the nonclassifiable states are more easily classified. The performance of model
      IV under the influence of noise was also investigated, and we found signs of an
      ergodic-nonergodic phase transition at some small finite positive level of noise,
      although the evidence is not entirely conclusive. We set an upper bound on the
      critical point for the transition, if any.

PMID- 30110836
TI  - Insights into noise modulation in oligomerization systems of increasing
      complexity.
AB  - Understanding under which conditions the increase of systems complexity is
      evolutionarily advantageous, and how this trend is related to the modulation of
      the intrinsic noise, are fascinating issues of utmost importance for synthetic
      and systems biology. To get insights into these matters, we analyzed a series of
      chemical reaction networks with different topologies and complexity, described by
      mass-action kinetics. We showed, analytically and numerically, that the global
      level of fluctuations at the steady state, measured by the sum over all species
      of the Fano factors of the number of molecules, is directly related to the
      network's deficiency. For zero-deficiency systems, this sum is constant and equal
      to the rank of the network. For higher deficiencies, additional terms appear in
      the Fano factor sum, which are proportional to the net reaction fluxes between
      the molecular complexes. We showed that the system's global intrinsic noise is
      reduced when all fluxes flow from lower to higher degree oligomers, or
      equivalently, towards the species of higher complexity, whereas it is amplified
      when the fluxes are directed towards lower complexity species.

PMID- 30110837
TI  - Growth and shape of a laboratory alluvial fan.
AB  - Using laboratory experiments, we investigate the influence of water and sediment
      discharges on the morphology of an alluvial fan. In our flume, a single-thread
      laminar river deposits corundum sand into a conical fan. We record the fan
      progradation with top-view images and measure its shape using the deformation of
      a Moire pattern. The fan remains virtually self-affine as it grows, with a nearly
      constant slope. We find that, when the sediment discharge is small, the
      longitudinal slope of the fan remains close to that of a river at the threshold
      for sediment transport. Consequently the slope depends on the water discharge
      only. A higher sediment discharge causes the fan's slope to depart from the
      threshold value. Due to the downstream decrease of the sediment load, this slope
      gets shallower towards the fan's toe. This mechanism generates a concave fan
      profile. This suggests that we could infer the sediment flux that feeds a fan
      based on its proximal slope.

PMID- 30110838
TI  - Lifting ordered surfaces: Ellipsoidal nematic shells.
AB  - When a material surface is functionalized so as to acquire some type of order,
      functionalization of which soft condensed matter systems have recently provided
      many interesting examples, the modeler faces an alternative. Either the order is
      described on the curved, physical surface where it belongs, or it is described on
      a flat surface that is unrolled as preimage of the physical surface under a
      suitable height function. This paper applies a general method that pursues the
      latter avenue by lifting whatever order tensor is deemed appropriate from a flat
      to a curved surface. We specialize this method to nematic shells, for which it
      also provides a simple but perhaps convincing interpretation of the outcomes of
      some molecular dynamics experiments on ellipsoidal shells.

PMID- 30110839
TI  - Intrinsic stochastic resonance via set-point variation.
AB  - In the present paper, the possibility of invoking stochastic resonance (SR,
      periodic and aperiodic) by regulating the operating value of an appropriate
      parameter is explored. The operating values of these parameters are defined as
      the set point of the system throughout the present paper. Brusselator, a
      mathematical model [I. Prigogine and R. Lefever, J. Chem. Phys. 48, 1695
      (1968)JCPSA60021-960610.1063/1.1668896] of nonlinear chemical reactions, is used
      for this purpose. We consider the effect of intrinsic noise in the Brusselator
      due to the Markovian nature of the chemical reactions. The stochastic time
      evolution is studied using the Gillespie algorithm [D. T. Gillespie, J. Comput.
      Phys. 22, 403 (1976)JCTPAH0021-999110.1016/0021-9991(76)90041-3], which is an
      exact stochastic simulation algorithm. We analyze the dependence of the resonance
      point on both the strength of the intrinsic noise as well as the distance from
      the bifurcation point. Subsequently, the phenomena of SR is explored using both
      periodic and aperiodic stimulus. It was found that, for a given system size, in
      both cases, SR is achieved by variation of the set point. Set-point variation can
      be achieved by regulating either the source concentration or the rate constants.
      Resonance is observed in both cases. However, this resonance occurs at different
      values of the set point, even with a fixed system size. This is clearly seen in
      the set-point versus system-size plane, where the resonance line has different
      slopes for the two scenarios. Our semianalytic treatment points to the fact that
      for a given system size intrinsic noise is affected differently for different
      methods involving the variation of the set point. This is explained by writing
      the corresponding chemical Langevin equation and comparing the various intrinsic
      noise sources.

PMID- 30110840
TI  - Structural bifurcation analysis in chemical reaction networks.
AB  - In living cells, chemical reactions form complex networks. Dynamics arising from
      such networks are the origins of biological functions. We propose a mathematical
      method to analyze bifurcation behaviors of network systems using their structures
      alone. Specifically, a whole network is decomposed into subnetworks, and for each
      of them the bifurcation condition can be studied independently. Further,
      parameters inducing bifurcations and chemicals exhibiting bifurcations can be
      determined on the network. We illustrate our theory using hypothetical and real
      networks.

PMID- 30110841
TI  - Regimes of wrinkling in an indented floating elastic sheet.
AB  - A thin, elastic sheet floating on the surface of a liquid bath wrinkles when
      poked at its center. We study the onset of wrinkling as well as the evolution of
      the pattern as indentation progresses far beyond the wrinkling threshold. We use
      tension field theory to describe the macroscopic properties of the deformed film
      and show that the system passes through a host of different regimes, even while
      the deflections and strains remain small. We show that the effect of the finite
      size of the sheet ultimately plays a key role in determining the location of the
      wrinkle pattern, and obtain scaling relations that characterize the number of
      wrinkles at threshold and its variation as the indentation progresses.

PMID- 30110842
TI  - Quantum corrections of work statistics in closed quantum systems.
AB  - We investigate quantum corrections to the classical work characteristic function
      (CF) as a semiclassical approximation to the full quantum work CF. In addition to
      explicitly establishing the quantum-classical correspondence of the Feynman-Kac
      formula, we find that these quantum corrections must be in even powers of h.
      Exact formulas of the lowest corrections (h^{2}) are proposed, and their physical
      origins are clarified. We calculate the work CFs for a forced harmonic oscillator
      and a forced quartic oscillator respectively to illustrate our results.

PMID- 30110843
TI  - Spatial characterization of turbulent channel flow via complex networks.
AB  - A network-based analysis of a turbulent channel flow numerically solved at
      Re_{tau}=180 is proposed as an innovative perspective for the spatial
      characterization of the flow field. Two spatial networks corresponding to the
      streamwise and wall-normal velocity components are built, where nodes represent
      portions of volume of the physical domain. For each network, links are active if
      the correlation coefficient of the corresponding velocity component between pairs
      of nodes is sufficiently high, thus unveiling the strongest kinematic relations.
      Several network measures are studied in order to explore the interrelations
      between nodes and their neighbors. Specifically, long-range links are localized
      between near-wall regions and associated with the temporal persistence of
      coherent patterns, namely high and low speed streaks. Furthermore, long-range
      links play a crucial role as intermediary for the kinematic information flow, as
      emerges from the analysis of indirect connections between nodes. The proposed
      approach provides a framework to investigate spatial structures of the turbulent
      dynamics, showing the full potential of complex networks. Although the network
      analysis is based on the two-point correlation, it is able to advance the level
      of information, by exploiting the texture created by active links in all
      directions. Based on the observed findings, the current approach can pave the way
      for an enhanced spatial interpretation of the turbulence dynamics.

PMID- 30110844
TI  - Complex network comparison based on communicability sequence entropy.
AB  - Identification and quantification of the structural dissimilarities between
      complex networks is a very important and challenging problem in network science.
      A simple and efficient way to quantify network differences remains unexplored.
      Although the methods for network comparison based on the probability distribution
      of a network descriptor have been shown to be effective for specific purposes,
      the information they provide is often limited or incomplete. In order to overcome
      the defect of the methods, here we use the communicability between two nodes to
      define the communicability sequence entropy of networks, and on the basis of this
      entropy measure, we propose a Jensen-Shannon divergence of two networks which can
      be used as natural distance measure between complex networks. By the extensive
      experiments, we find that the measure can accurately quantify the structural
      dissimilarities between synthetic networks. Most importantly, the measure can be
      able to identify the critical percolation probability of the random network in
      the evolution process, and it can also effectively guide us to choose a more
      suitable model to simulate real systems.

PMID- 30110845
TI  - Closed-form solutions for the Levy-stable distribution.
AB  - The Levy-stable distribution is the attractor of distributions which hold power
      laws with infinite variance. This distribution has been used in a variety of
      research areas; for example, in economics it is used to model financial market
      fluctuations and in statistical mechanics it is used as a numerical solution of
      fractional kinetic equations of anomalous transport. This function does not have
      an explicit expression and no uniform solution has been proposed yet. This paper
      presents a uniform analytical approximation for the Levy-stable distribution
      based on matching power series expansions. For this solution, the trans-stable
      function is defined as an auxiliary function which removes the numerical issues
      of the calculations of the Levy-stable distribution. Then, the uniform solution
      is proposed as a result of an asymptotic matching between two types of
      approximations called "the inner solution" and "the outer solution." Finally, the
      results of analytical approximation are compared to the numerical results of the
      Levy-stable distribution function, making this uniform solution valid to be
      applied as an analytical approximation.

PMID- 30110846
TI  - Equivalence of nonequilibrium ensembles in turbulence models.
AB  - Understanding under what conditions it is possible to construct equivalent
      ensembles is key to advancing our ability to connect microscopic and macroscopic
      properties of nonequilibrium statistical mechanics. In the case of fluid
      dynamical systems, one issue is to test whether different models for viscosity
      lead to the same macroscopic properties of the fluid systems in different
      regimes. Such models include, besides the standard choice of constant viscosity,
      cases where the time symmetry of the evolution equations is exactly preserved, as
      it must be in the corresponding microscopic systems, when available. Here a time
      reversible dynamics is obtained by imposing the conservation of global
      observables. We test the equivalence of reversible and irreversible ensembles for
      the case of a multiscale shell model of turbulence. We verify that the
      equivalence is obeyed for the mean values of macroscopic observables, up to an
      error that vanishes as the system becomes more and more chaotic.

PMID- 30110847
TI  - Directed polaron propagation in linear polypeptides induced by intramolecular
      vibrations and external electric pulses.
AB  - We study the propagation of alpha-helix polarons in a model describing the
      nonadiabatic interaction between an electron and a lattice of quantum mechanical
      oscillators at physiological temperature. We show that when excited by a
      subpicosecond electric pulse, as induced by experimentally observed subpicosecond
      charge separation, the polaron is displaced by up to hundreds of lattice sites
      before the electron becomes delocalised. We discuss biophysical implications of
      our results.

PMID- 30110848
TI  - Erratum: Spectral renormalization group for the Gaussian model and psi^{4} theory
      on nonspatial networks [Phys. Rev. E 92, 022106 (2015)].
AB  - This corrects the article DOI: 10.1103/PhysRevE.92.022106.

PMID- 30110849
TI  - Bifurcation diagrams in estimated parameter space using a pruned extreme learning
      machine.
AB  - We propose an algorithm to estimate parameter spaces by using a pruned extreme
      learning machine, but without using principal component analysis, and we plot
      bifurcation diagrams in the estimated parameter spaces to visualize changes in
      system patterns. The estimation of parameter spaces can predict changes in the
      behavior of a system when its parameters are changed. It can be very helpful to
      adjust the optimal parameters of unknown systems. In this paper, we estimate the
      dimension of parameter spaces using the singular values of trained synaptic
      weights and the parameter spaces based on the method proposed by Bagarinao et
      al., using a pruned extreme learning machine. We motivate this use of a pruned
      extreme learning machine through numerical experiments, with the estimation of
      the dimension of parameter spaces for various systems, and we show that the
      proposed method can successfully plot bifurcation diagrams in the estimated
      parameter spaces. In addition, we show the results of a bifurcation diagram in
      the estimated parameter space for maps that are nonlinear-in-parameters, since
      Bagarinao et al. limited their method to linear-in-parameters maps. In
      particular, we estimate the parameter spaces for a mathematical model of
      induction motor drives and for a model of vegetation biomass in ecosystems, which
      are both nonlinear-in-parameter maps corresponding to real-world systems.

PMID- 30110850
TI  - Maximum-entropy models reveal the excitatory and inhibitory correlation
      structures in cortical neuronal activity.
AB  - Maximum entropy models can be inferred from large datasets to uncover how
      collective dynamics emerge from local interactions. Here, such models are
      employed to investigate neurons recorded by multi-electrode arrays in the human
      and monkey cortex. Taking advantage of the separation of excitatory and
      inhibitory neuron types, we construct a model including this distinction. This
      approach allows us to shed light on differences between excitatory and inhibitory
      activity across different brain states such as wakefulness and deep sleep, in
      agreement with previous findings. Additionally, maximum entropy models can also
      unveil novel features of neuronal interactions, which are found to be dominated
      by pairwise interactions during wakefulness, but are population-wide during deep
      sleep. Overall, we demonstrate that maximum entropy models can be useful to
      analyze datasets with classified neuron types and to reveal the respective roles
      of excitatory and inhibitory neurons in organizing coherent dynamics in the
      cerebral cortex.

PMID- 30110851
TI  - Empirical observations of ultraslow diffusion driven by the fractional dynamics
      in languages.
AB  - Ultraslow diffusion (i.e., logarithmic diffusion) has been extensively studied
      theoretically but has hardly been observed empirically. In this paper, first, we
      find the ultraslow-like diffusion of the time series of word counts of already
      popular words by analyzing three different nationwide language databases: (i)
      newspaper articles (Japanese), (ii) blog articles (Japanese), and (iii) page
      views of Wikipedia (English, French, Chinese, and Japanese). Second, we use
      theoretical analysis to show that this diffusion is basically explained by the
      random walk model with the power-law forgetting with the exponent beta~0.5, which
      is related to the fractional Langevin equation. The exponent beta characterizes
      the speed of forgetting and beta~0.5 corresponds to (i) the border (or
      thresholds) between the stationary and the nonstationary and (ii) the right-in
      the-middle dynamics between the IID noise for beta=1 and the normal random walk
      for beta=0. Third, the generative model of the time series of word counts of
      already popular words, which is a kind of Poisson process with the Poisson
      parameter sampled by the above-mentioned random walk model, can almost reproduce
      not only the empirical mean-squared displacement but also the power spectrum
      density and the probability density function.

PMID- 30110852
TI  - Model reduction for Kuramoto models with complex topologies.
AB  - Synchronization of coupled oscillators is a ubiquitous phenomenon, occurring in
      topics ranging from biology and physics to social networks and technology. A
      fundamental and long-time goal in the study of synchronization has been to find
      low-order descriptions of complex oscillator networks and their collective
      dynamics. However, for the Kuramoto model, the most widely used model of coupled
      oscillators, this goal has remained surprisingly challenging, in particular for
      finite-size networks. Here, we propose a model reduction framework that
      effectively captures synchronization behavior in complex network topologies. This
      framework generalizes a collective coordinates approach for all-to-all networks
      [G. A. Gottwald, Chaos 25, 053111 (2015)CHAOEH1054-150010.1063/1.4921295] by
      incorporating the graph Laplacian matrix in the collective coordinates. We first
      derive low dimensional evolution equations for both clustered and nonclustered
      oscillator networks. We then demonstrate in numerical simulations for Erdos-Renyi
      networks that the collective coordinates capture the synchronization behavior in
      both finite-size networks as well as in the thermodynamic limit, even in the
      presence of interacting clusters.

PMID- 30110853
TI  - Coarsening and mechanics in the bubble model for wet foams.
AB  - Aqueous foams are an important model system that displays coarsening dynamics.
      Coarsening in dispersions and foams is well understood in the dilute and dry
      limits, where the gas fraction tends to zero and one, respectively. However,
      foams are known to undergo a jamming transition from a fluidlike to a solidlike
      state at an intermediate gas fraction phi_{c}. Much less is known about
      coarsening dynamics in wet foams near jamming, and the link to mechanical
      response, if any, remains poorly understood. Here we probe coarsening and
      mechanical response using numerical simulations of a variant of the Durian bubble
      model for wet foams. As in other coarsening systems we find a steady state
      scaling regime with an associated particle size distribution. We relate the time
      rate of evolution of the coarsening process to the wetness of the foam and
      identify a characteristic coarsening time that diverges approaching jamming. We
      further probe mechanical response of the system to strain while undergoing
      coarsening. There are two competing timescales, namely the coarsening time and
      the mechanical relaxation time. We relate these to the evolution of the elastic
      response and the mechanical structure.

PMID- 30110854
TI  - Molecular dynamics determination of liquid-vapor coexistence in molten alkali
      halides.
AB  - We show by extensive molecular dynamics simulations that accurate predictions of
      liquid-vapor coexistence in molten alkali halides can be achieved in terms of a
      rigid ion potential description in which temperature-dependent ionic diameters
      are employed. The new ionic sizes result from the fitting of the experimental
      isothermal compressibilities, a condition whose physical implications and
      consequences are illustrated. The same diameters also allow us to formulate
      confident predictions for the compressibilities of salts in cases where the
      experimental data are lacking. The extension of the present approach to molten
      alkali-halide mixtures and to other classes of molten salts is discussed.

PMID- 30110855
TI  - Asymptotic expansion and Pade approximants for acceleration-driven Poiseuille
      flow of a rarefied gas: Bulk hydrodynamics and rheology.
AB  - The perturbation expansion technique is employed to solve the Boltzmann equation
      for the acceleration-driven steady Poiseuille flow of a dilute molecular gas
      flowing through a planar channel. Neglecting wall effects and focusing only on
      the bulk hydrodynamics and rheology, the perturbation solution is sought around
      the channel centerline in powers of the strength of acceleration. To make
      analytical progress, the collision term has been approximated by the Bhatnagar
      Gross-Krook kinetic model for hard spheres, and the related problem for Maxwell
      molecules was analyzed previously by Tij and Santos [J. Stat. Phys. 76, 1399
      (1994)JSTPBS0022-471510.1007/BF02187068]. The analytical expressions for
      hydrodynamic (velocity, temperature, and pressure) and rheological fields (normal
      stress differences, shear viscosity, and heat flux) are obtained by retaining
      terms up to tenth order in acceleration, with one aim of the present work being
      to understand the convergence properties of the underlying perturbation series
      solutions. In addition, various rarefaction effects (e.g., the bimodal shape of
      the temperature profile, nonuniform pressure profile, normal-stress differences,
      and tangential heat flux) are also critically analyzed in the Poiseuille flow as
      functions of the local Froude number. The hydrodynamic and rheological fields
      evaluated at the channel centerline confirmed the oscillatory nature of the
      present series solutions (when terms of increasing order are sequentially
      included), signaling the well-known pitfalls of asymptotic expansion. The Pade
      approximation technique is subsequently applied to check the region of
      convergence of each series solution. It is found that the diagonal Pade
      approximants for rheological fields agree qualitatively with previous simulation
      data on acceleration-driven rarefied Poiseuille flow.

PMID- 30110856
TI  - Enhancing master-slave synchronization: The effect of using a dynamic coupling.
AB  - This paper introduces a modified master-slave synchronization scheme for
      dynamical systems. In contrast to the standard configuration, the slave system
      does not receive any driving signal from the master, but rather the interaction
      is through a linear dynamical system. The key feature of the proposed coupling
      scheme is that it induces synchronization in certain systems that cannot be
      synchronized when using the classical static interconnection. Likewise, the
      dynamic coupling achieves synchronization for arbitrarily large coupling strength
      values in certain systems for which the classical configuration is applicable
      only within a narrow interval of coupling strength values. The performance of the
      synchronization scheme is illustrated in pairs of identical chaotic and
      mechanical oscillators.

PMID- 30110857
TI  - Thermal conductivity at the high-density limit and the levitating granular
      cluster.
AB  - The granular Leidenfrost state consists of a dense granular cluster levitating
      above a hot granular gas. The density of particles inside the cluster can be very
      high and even close to the density of crystalline packing. To describe this state
      theoretically, one needs to know the density dependence of constitutive relations
      (pressure, heat losses, thermal conductivity) at these very high densities.
      However, the accurate expression for the coefficient of thermal conductivity is
      lacking. In this work, the constitutive relations were measured at high densities
      in molecular dynamics simulations in three different settings: a uniform freely
      cooling dense granulate (to measure heat losses), a uniform ensemble of
      elastically colliding particles (to measure pressure), and a dense granular
      medium between two thermal walls under gravity (to measure thermal conductivity).
      Next, the hydrodynamic equations with the resulting expressions were solved to
      describe the levitating cluster state in various parameter regimes. Separate
      molecular dynamics simulations were performed to test the theoretical predictions
      and measure the density and temperature profiles of the granular Leidenfrost
      state, and a good agreement with theoretical results was observed.

PMID- 30110858
TI  - Coherence and decoherence in quantum absorption refrigerators.
AB  - Absorption refrigerators transfer thermal energy from a cold reservoir to a hot
      reservoir using input energy from a third, so-called work reservoir. We examine
      the operation of quantum absorption refrigerators when coherences between
      eigenstates survive in the steady state limit. In our model, the working medium
      comprises a discrete, four-level system. Several studies on related setups have
      demonstrated the performance-enhancing potential of steady-state eigenbasis
      quantum coherences. By contrast, in our model such coherences generally quench
      the cooling current in the refrigerator, while minimally affecting the
      coefficient of performance (cooling efficiency). We rationalize the behavior of
      the four-level refrigerator by studying three-level model systems for energy
      transport and refrigeration. Our calculations further illuminate the shortcomings
      of secular quantum master equations and the necessity of employing dynamical
      equations of motion that retain couplings between population and coherences.

PMID- 30110859
TI  - Partition of common anesthetic molecules in the liquid disordered phase domain of
      a composite multicomponent membrane.
AB  - Despite a vast clinical application of anesthetics, the molecular level of
      understanding of general anesthesia is far from our reach. Using atomistic
      molecular dynamics simulation, we study the effects of common anesthetics:
      ethanol, chloroform, and methanol in the fully hydrated symmetric multicomponent
      lipid bilayer membrane comprised of an unsaturated palmitoyl-oleoyl-phosphatidyl
      choline (POPC), a saturated palmitoyl-sphingomyelin, and cholesterol, which
      exhibits phase coexistence of liquid-ordered (l_{o})-liquid-disordered (l_{d})
      phase domains. We find that the mechanical and physical properties such as the
      thickness and rigidity of the membrane are reduced while the lateral expansion of
      the membrane is exhibited in the presence of anesthetic molecules. Our simulation
      shows both lateral and transverse heterogeneity of the anesthetics in the
      composite multicomponent lipid membrane. Both ethanol and chloroform partition in
      the POPC-rich l_{d} phase domain, while methanol is distributed in both l_{o}
      l_{d} phase domains. Chloroform can penetrate deep into the membrane, while
      methanol partitions mostly at the water layer closed to the head group and
      ethanol at the neck of the lipids in the membrane.

PMID- 30110860
TI  - Axisymmetric lattice Boltzmann simulation of droplet impact on solid surfaces.
AB  - Droplet-solid interaction is a ubiquitous fluid phenomenon that underpins a wide
      range of applications. To further the understanding of this important problem, we
      use an axisymmetric lattice Boltzmann method (LBM) to model the droplet impact on
      a solid surface with different wettability. The method applies a popular free
      energy LBM developed by Lee and Liu [T. Lee and L. Liu, J. Comput. Phys. 229,
      8045 (2010)10.1016/j.jcp.2010.07.007] to simulate incompressible binary fluids
      with physical density and viscosity contrasts. The formulation is recast in
      cylindrical coordinates for modeling the normal impact of a three-dimensional
      (3D) droplet in the no-splashing regime, in which an axisymmetric flow is
      considered. The droplet deposits on or rebounds from the surface, governed by
      three key parameters: Weber number, Ohnesorge number, and equilibrium contact
      angle, which quantifies the surface wettability. We elucidate the distinct impact
      dynamics by probing droplet morphology and contact line behavior in great detail,
      which are quantitatively characterized by spreading factor, droplet aspect ratio,
      and dynamic contact angle. The simulations also resolve fluid velocity field
      inside and outside the droplet, which provides additional insight into the
      morphological evolution and mass-momentum transfer during impact. Explicit
      comparison between axisymmetric and conventional 2D LBM highlights the importance
      of axisymmetric terms in governing equations for reproducing physical impact
      behavior. The axisymmetric LBM significantly reduces computational cost as
      compared with 3D LBMs and offers an effective means to study droplet impact in
      applicable conditions.

PMID- 30110861
TI  - Collision-based understanding of the force law in granular impact dynamics.
AB  - We study the stopping force felt by an intruder impacting onto a granular medium.
      Variations in the shape of the intruder can influence the penetration depth by
      changing the inertial drag. We find this observed correlation can be explained by
      associating the velocity-dependent inertial drag to the energy dissipation that
      occurs through intermittent collisions of force-chain-like clusters, the mean
      behavior of which can be statistically described. In consequence, the stopping
      force can be captured through a proposed collisional model with good accuracy,
      and the observed impact dynamics data can be reproduced quantitatively.

PMID- 30110862
TI  - Network synchronization with periodic coupling.
AB  - The synchronization behavior of networked chaotic oscillators with periodic
      coupling is investigated. It is observed in simulations that the network
      synchronizability could be significantly influenced by tuning the coupling
      frequency, even making the network alternating between the synchronous and
      nonsynchronous states. Using the master stability function method, we conduct a
      detailed analysis of the influence of coupling frequency on network
      synchronizability and find that the network synchronizability is maximized at
      some characteristic frequencies comparable to the intrinsic frequency of the
      local dynamics. Moreover, it is found that as the amplitude of the coupling
      increases, the characteristic frequencies are gradually decreased. Using the
      finite-time Lyapunov exponent technique, we investigate further the mechanism for
      the maximized synchronizability and find that at the characteristic frequencies
      the power spectrum of the finite-time Lyapunov exponent is abruptly changed from
      the localized to broad distributions. When this feature is absent or not
      prominent, the network synchronizability is less influenced by the periodic
      coupling. Our study shows the efficiency of finite-time Lyapunov exponent in
      exploring the synchronization behavior of temporally coupled oscillators and
      sheds lights on the interplay between the system dynamics and structure in
      general temporal networks.

PMID- 30110863
TI  - Molecular mobility in driven monomeric and polymeric glasses.
AB  - We show that in monomeric supercooled liquids and glasses that are plastically
      flowing at a constant shear stress sigma while being deformed with strain rate
      epsilon[over ], the microscopic structural relaxation time tau_{str} is given by
      the universal relation sigma/G_{infinity}epsilon[over ] with G_{infinity} a
      modulus. This equality holds for all rheological regimes from temperatures above
      the glass transition all the way to the athermal limit, and arises from the
      competing effects of elastic loading and viscous dissipation. In macromolecular
      (polymeric) glasses, however, the stress decouples from this relaxation time and
      tau_{str} is in fact further reduced even though sigma rises during glassy strain
      hardening. We develop expressions to capture both effects and thus provide a
      framework for analyzing mobility measurements in glassy materials.

PMID- 30110864
TI  - Physical mechanism of the electron-ion coupled transverse instability in laser
      pressure ion acceleration for different regimes.
AB  - In radiation pressure ion acceleration (RPA) research, the transverse stability
      within laser plasma interaction has been a long-standing, crucial problem over
      the past decades. In this paper, we present a one-dimensional two-fluid theory
      extended from a recent work Wan et al. Phys. Rev. Lett. 117, 234801
      (2016)PRLTAO0031-900710.1103/PhysRevLett.117.234801 to clearly clarify the origin
      of the intrinsic transverse instability in the RPA process. It is demonstrated
      that the purely growing density fluctuations are more likely induced due to the
      strong coupling between the fast oscillating electrons and quasistatic ions via
      the ponderomotive force with spatial variations. The theory contains a full
      analysis of both electrostatic (ES) and electromagnetic modes and confirms that
      the ES mode actually dominates the whole RPA process at the early linear stage.
      By using this theory one can predict the mode structure and growth rate of the
      transverse instability in terms of a wide range of laser plasma parameters. Two
      dimensional particle-in-cell simulations are systematically carried out to verify
      the theory and formulas in different regimes, and good agreements have been
      obtained, indicating that the electron-ion coupled instability is the major
      factor that contributes the transverse breakup of the target in RPA process.

PMID- 30110865
TI  - Scaling properties of monolayer graphene away from the Dirac point.
AB  - The statistical properties of the carrier density profile of graphene in the
      ground state in the presence of particle-particle interaction and random charged
      impurity in zero gate voltage has been recently obtained by Najafi et al. [Phys.
      Rev. E 95, 032112 (2017)2470-004510.1103/PhysRevE.95.032112]. The nonzero
      chemical potential (MU) in gated graphene has nontrivial effects on electron-hole
      puddles, since it generates mass in the Dirac action and destroys the scaling
      behaviors of the effective Thomas-Fermi-Dirac theory. We provide detailed
      analysis on the resulting spatially inhomogeneous system in the framework of the
      Thomas-Fermi-Dirac theory for the Gaussian (white noise) disorder potential. We
      show that the chemical potential in this system as a random surface destroys the
      self-similarity, and also the charge field is non-Gaussian. We find that the two
      body correlation functions are factorized to two terms: a pure function of the
      chemical potential and a pure function of the distance. The spatial dependence of
      these correlation functions is double logarithmic, e.g., the two-point density
      correlation behaves like D_{2}(r,MU)?MU^{2}exp[-(
      a_{D}lnlnr^{beta_{D}})^{alpha_{D}}] (alpha_{D}=1.82, beta_{D}=0.263, and
      a_{D}=0.955). The Fourier power spectrum function also behaves like ln[S(q)]=
      beta_{S}^{-a_{S}}(lnq)^{a_{S}}+2lnMU (a_{S}=3.0+/-0.1 and beta_{S}=2.08+/-0.03)
      in contrast to the ordinary Gaussian rough surfaces for which a_{S}=1 and
      beta_{S}=1/2(1+alpha)^{-1} (alpha being the roughness exponent). The geometrical
      properties are, however, similar to the ungated (MU=0) case, with the exponents
      that are reported in the text.

PMID- 30110866
TI  - Solitons in one-dimensional mechanical linkage.
AB  - It has been observed that certain classical chains admit topologically protected
      zero-energy modes that are localized on the boundaries. The static features of
      such localized modes are captured by linearized equations of motion, but the
      dynamical features are governed by its nonlinearity. We study quasiperiodic
      solutions of nonlinear equations of motion of one-dimensional classical chains.
      Such quasi-periodic solutions correspond to periodic trajectories in the
      configuration space of the discrete systems, which allows us to define solitons
      without relying on a continuum theory. Furthermore, we study the dynamics of
      solitons in inhomogeneous systems by connecting two chains with distinct
      parameter sets, where transmission or reflection of solitons occurs at the
      boundary of the two chains.

PMID- 30110868
TI  - Stability analysis of a quantum cascade laser subject to phase-conjugate
      feedback.
AB  - We investigate the stability boundaries of a quantum cascade laser subject to
      phase-conjugate optical feedback. From a three-level model, we reduce our set of
      equations to the usual modified Lang-Kobayashi equations describing a
      semiconductor laser subject to phase-conjugate feedback. We then determine the
      Hopf bifurcation conditions, which we explore by using asymptotic methods. In the
      limit of large delays, we find approximations of the first Hopf bifurcation that
      is responsible for the destabilization of the system. We obtain an expression
      that depends only on three parameters: the feedback strength, the line-width
      enhancement factor, and the pump current. From this expression, we study the
      stability boundaries of our system. We compare our results with the initial three
      level model using a continuation method. We find qualitative and quantitative
      agreements of the stability boundaries with the two methods. Finally, we compare
      our findings with the ones obtained for a quantum cascade laser subject to
      conventional optical feedback.

PMID- 30110867
TI  - Force distributions in frictional granular media.
AB  - We report a joint experimental and theoretical investigation of the probability
      distribution functions (PDFs) of the normal and tangential (frictional) forces in
      amorphous frictional media. We consider both the joint PDF of normal and
      tangential forces together, and the marginal PDFs of normal forces separately and
      tangential forces separately. A maximum entropy formalism is utilized for all
      these cases after identifying the appropriate constraints. Excellent agreements
      with both experimental and simulation data are reported. The proposed joint PDF
      predicts giant slip events at low pressures, again in agreement with
      observations.

PMID- 30110869
TI  - Quasispecies model of evolution with migration.
AB  - We consider the model of asexual evolution with migration, which was proposed by
      Waclaw et al. [Phys. Rev. Lett. 105, 268101 (2010)PRLTAO0031
      900710.1103/PhysRevLett.105.268101]. This model setting is based on the standard
      mutation scheme from the quasispecies theory but with replicators moving from one
      habitat to another. The primary goal is to solve exactly the infinite population
      genome length version of the model for the independent random distribution of
      fitnesses considered in the original paper. Moreover, we propose the analytical
      solution for the single peak and the symmetric fitness landscape. Our analytical
      solution is exact at the limit of large N. We found two phases-the correlated
      phase with the identical distributions of mutations in both habitats and the
      uncorrelated phase where the second habitat is choosing another peak of
      distribution in sequence space compared to the peak in the first habitat.

PMID- 30110870
TI  - Color-gradient lattice Boltzmann model with nonorthogonal central moments:
      Hydrodynamic melt-jet breakup simulations.
AB  - We develop a lattice Boltzmann (LB) model for immiscible two-phase flow
      simulations with central moments (CMs). This successfully combines a three
      dimensional nonorthogonal CM-based LB scheme [De Rosis, Phys. Rev. E 95, 013310
      (2017)2470-004510.1103/PhysRevE.95.013310] with our previous color-gradient LB
      model [Saito, Abe, and Koyama, Phys. Rev. E 96, 013317 (2017)2470
      004510.1103/PhysRevE.96.013317]. Hydrodynamic melt-jet breakup simulations show
      that the proposed model is significantly more stable, even for flow with
      extremely high Reynolds numbers, up to O(10^{6}). This enables us to investigate
      the phenomena expected under actual reactor conditions.

PMID- 30110871
TI  - Precise algorithms to compute surface correlation functions of two-phase
      heterogeneous media and their applications.
AB  - The quantitative characterization of the microstructure of random heterogeneous
      media in d-dimensional Euclidean space R^{d} via a variety of n-point correlation
      functions is of great importance, since the respective infinite set determines
      the effective physical properties of the media. In particular, surface-surface
      F_{ss} and surface-void F_{sv} correlation functions (obtainable from radiation
      scattering experiments) contain crucial interfacial information that enables one
      to estimate transport properties of the media (e.g., the mean survival time and
      fluid permeability) and complements the information content of the conventional
      two-point correlation function. However, the current technical difficulty
      involved in sampling surface correlation functions has been a stumbling block in
      their widespread use. We first present a concise derivation of the small-r
      behaviors of these functions, which are linked to the mean curvature of the
      system. Then we demonstrate that one can reduce the computational complexity of
      the problem, without sacrificing accuracy, by extracting the necessary
      interfacial information from a cut of the d-dimensional statistically homogeneous
      and isotropic system with an infinitely long line. Accordingly, we devise
      algorithms based on this idea and test them for two-phase media in continuous and
      discrete spaces. Specifically for the exact benchmark model of overlapping
      spheres, we find excellent agreement between numerical and exact results. We
      compute surface correlation functions and corresponding local surface-area
      variances for a variety of other model microstructures, including hard spheres in
      equilibrium, decorated "stealthy" patterns, as well as snapshots of evolving
      pattern formation processes (e.g., spinodal decomposition). It is demonstrated
      that the precise determination of surface correlation functions provides a
      powerful means to characterize a wide class of complex multiphase
      microstructures.

PMID- 30110872
TI  - Refrigeration beyond weak internal coupling.
AB  - We investigate the performance of a three-spin quantum absorption refrigerator
      using a refined open quantum system model valid across all interspin coupling
      strengths. It describes the transition between previous approximate models for
      the weak and the ultrastrong coupling limit, and it predicts optimal
      refrigeration for moderately strong coupling, where both approximations are
      inaccurate. Two effects impede a more effective cooling: the coupling between the
      spins no longer reduces to a simple resonant energy exchange (the rotating wave
      approximation fails), and the interactions with the thermal baths become
      sensitive to the level splitting, thus opening additional heat channels between
      the reservoirs. We identify the modified conditions of refrigeration as a
      function of the interspin coupling strength, and we show that, contrary to
      intuition, a high-temperature work reservoir thwarts refrigeration in the strong
      coupling regime.

PMID- 30110873
TI  - Three-dimensional multidomain lattice Boltzmann grid refinement for passive
      scalar transport.
AB  - Simulations of passive scalar transport on a three-dimensional (3D)
      multiresolution grid are presented within the framework of single relaxation time
      lattice Boltzmann method. The combined modeling of the fluid flow and scalar
      transport is handled by a double distribution function approach in which the
      velocity in the fluid flow equation is solved first and then copied to the scalar
      equation to solve the corresponding scalar quantities. A 3D scaling technique,
      considering both external forces and scalar source terms, and two-dimensional
      bicubic interpolation scheme are developed for coupling nonequilibrium velocity
      and scalar distributions on the interfaces of different resolution grids. The
      proposed algorithm is validated for three benchmark cases, i.e., the forced
      convection in a 3D channel, natural convection in a cubical cavity, and turbulent
      channel flow with heat transfer. Good agreements are found between the present
      predictions and previous data, which confirms the capability of the proposed
      method for the computation of passive scalar transport in 3D domains.

PMID- 30110874
TI  - Cavitation in a liquid-filled cavity surrounded by an elastic medium:
      Intercoupling of cavitation events in neighboring cavities.
AB  - The subject of the present theoretical study is the dynamics of a cavitation
      bubble in a spherical liquid-filled cavity surrounded by an infinite elastic
      solid. Two objectives are pursued. The first is to derive equations for the
      velocity and pressure fields throughout the liquid filling the cavity and
      equations for the stress and strain fields throughout the solid medium
      surrounding the cavity. This derivation is based on the results of our previous
      paper [A. A. Doinikov et al., Phys. Rev. E 97, 013108
      (2018)10.1103/PhysRevE.97.013108], where equations for the evolution of a bubble
      inside a cavity were derived. The second objective is to apply the equations
      obtained at the first step of the study to ascertain if the cavitation process in
      one cavity can trigger the nucleation in a neighboring cavity. To this end, we
      consider a neighboring cavity in which a cavitation bubble is absent. We derive
      equations that describe the disturbance of the liquid pressure inside the second
      cavity, assuming this disturbance to be caused by the cavitation process in the
      first cavity. The developed theory is then used to perform numerical simulations.
      The results of the simulations show that the magnitude of the background negative
      pressure inside the second cavity increases at the second half period of the
      pressure disturbance, which in turn enhances the probability of nucleation in the
      second cavity.

PMID- 30110875
TI  - Thermal bath engineering for swift equilibration.
AB  - We provide a theoretical and experimental protocol that dynamically controls the
      effective temperature of a thermal bath, through a well-designed noise
      engineering. We use this powerful technique to shortcut the relaxation of an
      overdamped Brownian particle in a quadratic potential by a joint time engineering
      of the confinement strength and of the noise. For an optically trapped colloid,
      we report an equilibrium recovery time reduced by about two orders of magnitude
      compared to the natural relaxation time. Our scheme paves the way towards
      reservoir engineering in nanosystems.

PMID- 30110876
TI  - Superposition principle for the simultaneous optimization of collective
      responses.
AB  - We study the dynamics of sets of independent systems, all of which are coupled to
      the same time-dependent external force. Using optimal control theory, we compute
      the most efficient temporal pulse shape for this force that can maximize
      simultaneously the collective response of these systems. This response can be a
      weighted sum of all amplitudes at the final interaction time. Remarkably, it
      turns out that for certain systems this optimal force for the collective response
      can be related to the individual forces that would optimize each system
      separately. We illustrate this superposition principle for the simultaneous
      optimization of collective responses with numerical and also analytical solutions
      for sets of damped linear and nonlinear oscillators. We also apply this principle
      to predict the optimal temporal profile of a laser pulse that can maximize the
      final macroscopic polarization (total dipole moment) of a set of quantum
      mechanical two-level atoms.

PMID- 30110877
TI  - Mechanical spectral hole burning of an entangled polymer solution in the stress
      controlled domain.
AB  - Nonresonant spectral hole burning has proven to be a versatile method to
      characterize the dynamics of complex fluids, including polymers. Early work
      focused on dielectric susceptibility measurements in glass forming liquids, while
      recent work from our lab used mechanical viscoelastic measurements to investigate
      polymer melts and solutions. While the observed results were similar, the
      interpretations were different, with the former being interpreted by attributing
      the "holes" in the response as being due to dynamic heterogeneity in the system
      that is related to the glass or other transition, while the latter was
      interpreted in a way that suggested that the observed holes depend on the type of
      dynamics (Rouse, terminal, etc.) rather than an identifiable spatial
      heterogeneity. In this work, we have expanded mechanical spectral hole burning
      (MSHB) into the stress-controlled domain and carried out experiments in the
      rubbery regime of a polystyrene solution, similar to one which was tested
      previously with strain-controlled MSHB. The effects of pump stress amplitude,
      pump frequency, and waiting time were investigated. The mechanical holes in both
      directions (vertical and horizontal) were successfully burned, unlike the strain
      controlled MSHB experiments on the same polystyrene solution, in which vertical
      holes were at best incomplete. The hole intensity exhibits a linear relationship
      with the amount of energy dissipated in the system during the large mechanical
      pump modification. The results suggest that the stress-controlled MSHB can be
      combined with strain-controlled MSHB to build a more complete framework to
      investigate the dynamics of polymeric materials and is consistent with the
      dynamic heterogeneity being related to the type of dynamics rather than to
      localized heating effects.

PMID- 30110878
TI  - Kinks in chains with on-site bistable nondegenerate potential: Beyond traveling
      waves.
AB  - This paper revisits the well-known transition fronts (kinks) in chains of coupled
      oscillators with nondegenerate on-site potentials. Usually, such transition
      fronts are considered in terms of traveling-wave solutions. We explore the loss
      of stability of such traveling waves. Generically, it corresponds to one of the
      common scenarios for fixed points of discrete maps. For example, one can
      encounter the quasiperiodic kink propagation (due to Hopf bifurcation), or the
      Feigenbaum cascade of period doublings, leading to a chaoticlike propagation
      pattern. The aforementioned scenarios show up, for instance, for triparabolic and
      phi^{4} on-site potentials. Numeric evidence suggests that the loss of stability
      occurs due to resonances between the frequency associated with the kink
      propagation, and the linear band gaps of the chain. Particular resonance
      mechanisms are model dependent. For the classical Atkinson-Cabrera model with a
      biparabolic on-site potential, the stability threshold is estimated by the simple
      means of linear algebra. The loss of stability in this model occurs through Hopf
      bifurcation. The results are in good agreement with numerical simulations.

PMID- 30110879
TI  - Correction: Shaped Magnetic Field Pulses by Multi-Coil Repetitive Transcranial
      Magnetic Stimulation (rTMS) Differentially Modulate Anterior Cingulate Cortex
      Responses and Pain in Volunteers and Fibromyalgia Patients.

PMID- 30110880
TI  - Device-Based Security to Improve User Privacy in the Internet of Things ?.
AB  - The use of Internet of Things (IoT) is rapidly growing and a huge amount of data
      is being generated by IoT devices. Cloud computing is a natural candidate to
      handle this data since it has enough power and capacity to process, store and
      control data access. Moreover, this approach brings several benefits to the IoT,
      such as the aggregation of all IoT data in a common place and the use of cloud
      services to consume this data and provide useful applications. However, enforcing
      user privacy when sending sensitive information to the cloud is a challenge. This
      work presents and evaluates an architecture to provide privacy in the integration
      of IoT and cloud computing. The proposed architecture, called PROTeCt-Privacy
      aRquitecture for integratiOn of internet of Things and Cloud computing, improves
      user privacy by implementing privacy enforcement at the IoT devices instead of at
      the gateway, as is usually done. Consequently, the proposed approach improves
      both system security and fault tolerance, since it removes the single point of
      failure (gateway). The proposed architecture is evaluated through an analytical
      analysis and simulations with severely constrained devices, where delay and
      energy consumption are evaluated and compared to other architectures. The
      obtained results show the practical feasibility of the proposed solutions and
      demonstrate that the overheads introduced in the IoT devices are worthwhile
      considering the increased level of privacy and security.

PMID- 30110881
TI  - Synthesis of Small Ce3+-Er3+-Yb3+ Tri-Doped BaLuF5 Active-Core-Active-Shell
      Active-Shell Nanoparticles with Strong Down Conversion Luminescence at 1.5 MUm.
AB  - Small fluoride nanoparticles (NPs) with strong down-conversion (DC) luminescence
      at 1.5 MUm are quite desirable for optical fiber communication systems.
      Nevertheless, a problem exists regarding how to synthesize small fluoride NPs
      with strong DC emission at 1.5 MUm. Herein, we propose an approach to improve 1.5
      MUm emission of BaLuF5:Yb3+,Er3+ NPs by way of combining doping Ce3+ ions and
      coating multiple BaLuF5: Yb3+ active-shells. We prepared the
      BaLuF5:18%Yb3+,2%Er3+,2%Ce3+ NPs through a high-boiling solvent method. The
      effect of Ce3+ concentration on the DC luminescence was systematically
      investigated in the BaLuF5:Yb3+,Er3+ NPs. Under a 980 nm laser excitation, the
      intensities of 1.53 MUm emission of BaLuF5:18%Yb3+,2%Er3+,2%Ce3+ NPs was enhanced
      by 2.6 times comparing to that of BaLuF5:18%Yb3+,2%Er3+ NPs since the energy
      transfer between Er3+ and Ce3+ ions: Er3+:4I11/2 (Er3+) + 2F5/2 (Ce3+) -> 4I13/2
      (Er3+) + 2F7/2 (Ce3+). Then, we synthesized
      BaLuF5:18%Yb3+,2%Er3+,2%Ce3+@BaLuF5:5%Yb3+@BaLuF5:5%Yb3+ core-active-shell-active
      shell NPs via a layer-by-layer strategy. After coating two BaLuF5:Yb3+ active
      shell around BaLuF5:Yb3+,Er3+,Ce3+ NPs, the intensities of the 1.53 MUm emission
      was enhanced by 44 times compared to that of BaLuF5:Yb3+,Er3+ core NPs, since the
      active-shells could be used to not only suppress surface quenching but also to
      transfer the pump light to the core region efficiently through Yb3+ ions inside
      the active-shells.

PMID- 30110884
TI  - A Class of Rate-Independent Lower-Order Gradient Plasticity Theories:
      Implementation and Application to Disc Torsion Problem.
AB  - As the characteristic scale of products and production processes decreases, the
      plasticity phenomena observed start to deviate from those evidenced at the
      macroscale. The current research aims at investigating this gap using a lower
      order gradient enhanced approach both using phenomenological continuum level as
      well as crystal plasticity models. In the phenomenological approach, a physically
      based hardening model relates the flow stress to the density of dislocations
      where it is assumed that the sources of immobile dislocations are both
      statistically stored (SSDs) as well as geometrically necessary dislocations
      (GNDs). In the crystal plasticity model, the evolution of the critical resolved
      shear stress is also defined based on the total number of dislocations. The GNDs
      are similarly incorporated in the hardening based on projecting the plastic
      strain gradients through the Burgers tensor on slip systems. A rate-independent
      formulation is considered that eliminates any artificial inhomogeneous hardening
      behavior due to numerical stabilization. The behavior of both models is compared
      in simulations focusing on the effect of structurally imposed gradients versus
      the inherent gradients arising in crystal plasticity simulations.

PMID- 30110883
TI  - Chia Seed Does Not Improve Cognitive Impairment in SAMP8 Mice Fed with High Fat
      Diet.
AB  - BACKGROUND: Chia seed is an ancient seed with the richest plant source of alpha
      linolenic acid, which has been demonstrated to improve metabolic syndrome
      associated risk factors. Under high fat diet (HFD) condition, the senescence
      accelerated mouse-prone 8 (SAMP8) mice demonstrated worsen Alzheimer's disease
      (AD) related pathology compared to low fat diet fed SAMP8 mice. OBJECTIVE: To
      explore whether chia seed supplementation might improve cognitive impairment
      under aging and metabolic stress via high fat diet (HFD) fed SAMP8 mice as a
      model. DESIGN: SAMP8 mice and senescence-accelerated mouse-resistant 1 (SAMR1)
      were randomized into 4 groups, i.e., SAMR1 low fat diet group (SAMR1-LFD), SAMP8
      HFD and SAMP8-HFD group supplemented with 10% chia seed (SAMP8-HFD+Chia). At the
      end of the intervention, cognitive function was measured via Morris water maze
      (MWM) test. Hippocampus and parietal cortex were dissected for further analysis
      to measure key markers involved AD pathology including Abeta, tau and neuro
      inflammation. RESULTS: During navigation trials of MWM test, mice in SAMP8-LFD
      group demonstrated impaired learning ability compared to SAMR1-LFD group, and
      chia seed had no effect on learning and memory ability for HFD fed SAMP8 mice. As
      for Alzheimer's disease (AD) related pathology, chia seed not only increased
      alpha-secretase such as ADAM10 and insulin degrading enzyme (IDE), but also
      increased beta-secretase including beta-secretase 1 (BACE1) and cathepsin B, with
      an overall effects of elevation in the hippocampal Abeta42 level; chia seed
      slightly reduced p-Tauser404 in the hippocampus; while an elevation in neuro
      inflammation with the activation of glial fibrillary acidic protein (GFAP) and
      Ibalpha-1 were observed post chia seed supplementation. CONCLUSIONS: Chia seed
      supplementation did not improve cognitive impairment via MWM in HFD fed SAMP8
      mice. This might be associated with that chia seed increased key enzymes involved
      both in non-amyloidogenic and amyloidogenic pathways, and neuro-inflammation.
      Future studies are necessary to confirm our present study.

PMID- 30110882
TI  - The Unfolded Protein Response Pathway in the Yeast Kluyveromyces lactis. A
      Comparative View among Yeast Species.
AB  - Eukaryotic cells have evolved signalling pathways that allow adaptation to
      harmful conditions that disrupt endoplasmic reticulum (ER) homeostasis. When the
      function of the ER is compromised in a condition known as ER stress, the cell
      triggers the unfolded protein response (UPR) in order to restore ER homeostasis.
      Accumulation of misfolded proteins due to stress conditions activates the UPR
      pathway. In mammalian cells, the UPR is composed of three branches, each
      containing an ER sensor (PERK, ATF6 and IRE1). However, in yeast species, the
      only sensor present is the inositol-requiring enzyme Ire1. To cope with unfolded
      protein accumulation, Ire1 triggers either a transcriptional response mediated by
      a transcriptional factor that belongs to the bZIP transcription factor family or
      an mRNA degradation process. In this review, we address the current knowledge of
      the UPR pathway in several yeast species: Saccharomyces cerevisiae,
      Schizosaccharomyces pombe, Candida glabrata, Cryptococcus neoformans, and Candida
      albicans. We also include unpublished data on the UPR pathway of the budding
      yeast Kluyveromyces lactis. We describe the basic components of the UPR pathway
      along with similarities and differences in the UPR mechanism that are present in
      these yeast species.

PMID- 30110885
TI  - Herpes Simplex Virus Vectors for Gene Transfer to the Central Nervous System.
AB  - Neurodegenerative diseases (NDs) have a profound impact on human health worldwide
      and their incidence is predicted to increase as the population ages. ND severely
      limits the quality of life and leads to early death. Aside from treatments that
      may reduce symptoms, NDs are almost completely without means of therapeutic
      intervention. The genetic and biochemical basis of many NDs is beginning to
      emerge although most have complex etiologies for which common themes remain
      poorly resolved. Largely relying on progress in vector design, gene therapy is
      gaining increasing support as a strategy for genetic treatment of diseases. Here
      we describe recent developments in the engineering of highly defective herpes
      simplex virus (HSV) vectors suitable for transfer and long-term expression of
      large and/or multiple therapeutic genes in brain neurons in the complete absence
      of viral gene expression. These advanced vector platforms are safe, non
      inflammatory, and persist in the nerve cell nucleus for life. In the near term,
      it is likely that HSV can be used to treat certain NDs that have a well-defined
      genetic cause. As further information on disease etiology becomes available,
      these vectors may take on an expanded role in ND therapies, including gene
      editing and repair.

PMID- 30110886
TI  - The Characterization of Arabidopsis mterf6 Mutants Reveals a New Role for mTERF6
      in Tolerance to Abiotic Stress.
AB  - Exposure of plants to abiotic stresses, such as salinity, cold, heat, or drought,
      affects their growth and development, and can significantly reduce their
      productivity. Plants have developed adaptive strategies to deal with situations
      of abiotic stresses with guarantees of success, which have favoured the expansion
      and functional diversification of different gene families. The family of
      mitochondrial transcription termination factors (mTERFs), first identified in
      animals and more recently in plants, is likely a good example of this. In plants,
      mTERFs are located in chloroplasts and/or mitochondria, participate in the
      control of organellar gene expression (OGE), and, compared with animals, the
      mTERF family is expanded. Furthermore, the mutations in some of the hitherto
      characterised plant mTERFs result in altered responses to salt, high light, heat,
      or osmotic stress, which suggests a role for these genes in plant adaptation and
      tolerance to adverse environmental conditions. In this work, we investigated the
      effect of impaired mTERF6 function on the tolerance of Arabidopsis to salt,
      osmotic and moderate heat stresses, and on the response to the abscisic acid
      (ABA) hormone, required for plants to adapt to abiotic stresses. We found that
      the strong loss-of-function mterf6-2 and mterf6-5 mutants, mainly the former,
      were hypersensitive to NaCl, mannitol, and ABA during germination and seedling
      establishment. Additionally, mterf6-5 exhibited a higher sensitivity to moderate
      heat stress and a lower response to NaCl and ABA later in development. Our
      computational analysis revealed considerable changes in the mTERF6 transcript
      levels in plants exposed to different abiotic stresses. Together, our results
      pinpoint a function for Arabidopsis mTERF6 in the tolerance to adverse
      environmental conditions, and highlight the importance of plant mTERFs, and hence
      of OGE homeostasis, for proper acclimation to abiotic stress.

PMID- 30110887
TI  - Protein Intake during the First Two Years of Life and Its Association with Growth
      and Risk of Overweight.
AB  - Growth patterns early in life could exert a long-term impact on overweight and
      obesity development. Among all potential manipulative factors, infant diet is one
      of the most influential and could affect growth and subsequent health status
      during adolescence and adulthood. Dietary protein, as an important macronutrient
      in infants' diet, has been of special interest to researchers. Compared with
      human milk, infant formula tends to have a higher protein content and is
      associated with greater weight gain and later-in-life obesity risk. However, the
      effect of protein from other sources on infant growth trajectories during
      complementary feeding is not clear. Emerging research suggests that meat protein
      during early complementary feeding promotes linear growth while not increasing
      risk of overweight compared with dairy protein; and the gut microbiota might be a
      mediator between protein quality and growth trajectories. This review addresses
      the current knowledge of protein intake from birth to 24 months and its
      relationship with growth and risk of overweight.

PMID- 30110888
TI  - Investigations on the Electrochemical Atomic Layer Growth of Bi2Se3 and the
      Surface Limited Deposition of Bismuth at the Silver Electrode.
AB  - The Electrochemical Atomic Layer Deposition (E-ALD) technique is used for the
      deposition of ultrathin films of bismuth (Bi) compounds. Exploiting the E-ALD, it
      was possible to obtain highly controlled nanostructured depositions as needed,
      for the application of these materials for novel electronics (topological
      insulators), thermoelectrics and opto-electronics applications. Electrochemical
      studies have been conducted to determine the Underpotential Deposition (UPD) of
      Bi on selenium (Se) to obtain the Bi2Se3 compound on the Ag (111) electrode.
      Verifying the composition with X-ray Photoelectron Spectroscopy (XPS) showed
      that, after the first monolayer, the deposition of Se stopped. Thicker deposits
      were synthesized exploiting a time-controlled deposition of massive Se. We then
      investigated the optimal conditions to deposit a single monolayer of metallic Bi
      directly on the Ag.

PMID- 30110889
TI  - Design of a Scaffold Parameter Selection System with Additive Manufacturing for a
      Biomedical Cell Culture.
AB  - Open-source 3D printers mean objects can be quickly and efficiently produced.
      However, design and fabrication parameters need to be optimized to set up the
      correct printing procedure; a procedure in which the characteristics of the
      printing materials selected for use can also influence the process. This work
      focuses on optimizing the printing process of the open-source 3D extruder machine
      RepRap, which is used to manufacture poly(epsilon-caprolactone) (PCL) scaffolds
      for cell culture applications. PCL is a biocompatible polymer that is free of
      toxic dye and has been used to fabricate scaffolds, i.e., solid structures
      suitable for 3D cancer cell cultures. Scaffold cell culture has been described as
      enhancing cancer stem cell (CSC) populations related to tumor chemoresistance
      and/or their recurrence after chemotherapy. A RepRap BCN3D+ printer and 3 mm PCL
      wire were used to fabricate circular scaffolds. Design and fabrication parameters
      were first determined with SolidWorks and Slic3r software and subsequently
      optimized following a novel sequential flowchart. In the flowchart described
      here, the parameters were gradually optimized step by step, by taking several
      measurable variables of the resulting scaffolds into consideration to guarantee
      high-quality printing. Three deposition angles (45 degrees , 60 degrees  and 90
      degrees ) were fabricated and tested. MCF-7 breast carcinoma cells and NIH/3T3
      murine fibroblasts were used to assess scaffold adequacy for 3D cell cultures.
      The 60 degrees  scaffolds were found to be suitable for the purpose. Therefore,
      PCL scaffolds fabricated via the flowchart optimization with a RepRap 3D printer
      could be used for 3D cell cultures and may boost CSCs to study new therapeutic
      treatments for this malignant population. Moreover, the flowchart defined here
      could represent a standard procedure for non-engineers (i.e., mainly physicians)
      when manufacturing new culture systems is required.

PMID- 30110890
TI  - Unified Channel Management for Cognitive Radio Sensor Networks Aided Internet of
      Things.
AB  - Cognitive capabilities are indispensable for the Internet of Things (IoT) not
      only to equip them with learning, thinking, and decision-making capabilities but
      also to cater to their unprecedented huge spectrum requirements due to their
      gigantic numbers and heterogeneity. Therefore, in this paper, a novel unified
      channel management framework (CMF) is introduced for cognitive radio sensor
      networks (CRSNs), which comprises an (1) opportunity detector (ODR), (2)
      opportunity scheduler (OSR), and (3) opportunity ranker (ORR) to specifically
      address the immense and diverse spectrum requirements of CRSN-aided IoT. The
      unified CMF is unique for its type as it covers all three angles of spectrum
      management. The ODR is a double threshold based multichannel spectrum sensor that
      allows an IoT device to concurrently sense multiple channels to maximize spectrum
      opportunities. OSR is an integer linear programming (ILP) based channel
      allocation mechanism that assigns channels to heterogeneous IoT devices based on
      their minimal quality of service (QoS) requirements. ORR collects feedback from
      IoT devices about their transmission experience and generates special channel
      sensing order (CSO) for each IoT device based on the data rate and idle-time
      probabilities. The simulation results demonstrate that the proposed CMF
      outperforms the existing ones in terms of collision probability, detection
      probability, blocking probability, idle-time probability, and data rate.

PMID- 30110891
TI  - Fine-Grained Face Annotation Using Deep Multi-Task CNN.
AB  - We present a multi-task learning-based convolutional neural network (MTL-CNN)
      able to estimate multiple tags describing face images simultaneously. In total,
      the model is able to estimate up to 74 different face attributes belonging to
      three distinct recognition tasks: age group, gender and visual attributes (such
      as hair color, face shape and the presence of makeup). The proposed model shares
      all the CNN's parameters among tasks and deals with task-specific estimation
      through the introduction of two components: (i) a gating mechanism to control
      activations' sharing and to adaptively route them across different face
      attributes; (ii) a module to post-process the predictions in order to take into
      account the correlation among face attributes. The model is trained by fusing
      multiple databases for increasing the number of face attributes that can be
      estimated and using a center loss for disentangling representations among face
      attributes in the embedding space. Extensive experiments validate the
      effectiveness of the proposed approach.

PMID- 30110892
TI  - Research on Construction Workers' Activity Recognition Based on Smartphone.
AB  - This research on identification and classification of construction workers'
      activity contributes to the monitoring and management of individuals. Since a
      single sensor cannot meet management requirements of a complex construction
      environment, and integrated multiple sensors usually lack systemic flexibility
      and stability, this paper proposes an approach to construction-activity
      recognition based on smartphones. The accelerometers and gyroscopes embedded in
      smartphones were utilized to collect three-axis acceleration and angle data of
      eight main activities with relatively high frequency in simulated floor
      reinforcing steel work. Data acquisition from multiple body parts enhanced the
      dimensionality of activity features to better distinguish between different
      activities. The CART algorithm of a decision tree was adopted to build a
      classification training model whose effectiveness was evaluated and verified
      through cross-validation. The results showed that the accuracy of classification
      for overall samples was up to 89.85% and the accuracy of prediction was 94.91%.
      The feasibility of using smartphones as data-acquisition tools in construction
      management was verified. Moreover, it was proved that the combination of a
      decision-tree algorithm with smartphones could achieve complex activity
      classification and identification.

PMID- 30110894
TI  - The Different Physical and Behavioural Characteristics of Zoo Mammals That
      Influence Their Response to Visitors.
AB  - The factors underlying the 'zoo visit effect' (changes in animal
      behaviour/physiology in response to visitor presence) are still poorly
      understood, despite it being widely investigated. The present study examined the
      effect of zoo visitors on the behaviour of 17 different species of mammals at the
      Belo Horizonte Zoo, Minas Gerais, Brazil. The behaviour of the animals was
      recorded using scan (focal in one case) sampling with instantaneous recording of
      behaviour, during 12 continuous months. Data were analysed using a comparative
      method examining five different factors: diet, body weight, stratum occupied,
      activity cycle, and habitat, as well as three different visitor categories: small
      and quiet audience, medium size audience and medium noise, and large size and
      loud audience. Significant changes in the behaviour for each factor, especially
      increases in locomotor and resting behaviour, were observed in response to
      different visitor categories. The factors that most explained responses to
      visitor categories were habitat and activity cycle. Species from closed habitats
      compared to open habitats were significantly more impacted (more behaviour
      affected), probably, because they are, evolutionarily, less accustomed to visual
      contact with people. Diurnal species showed more behavioural changes than
      nocturnal ones, possibly, because they were being observed during their normal
      activity cycle. These results may help zoos identify which mammal species are
      most susceptible to the zoo visitor effect, and consequently, be more pro-active
      in the use of mitigating strategies.

PMID- 30110895
TI  - Almond Shell as a Microporous Carbon Source for Sustainable Cathodes in Lithium
      Sulfur Batteries.
AB  - A microporous carbon derived from biomass (almond shells) and activated with
      phosphoric acid was analysed as a cathodic matrix in Li-S batteries. By studying
      the parameters of the carbonization process of this biomass residue, certain
      conditions were determined to obtain a high surface area of carbon (967 m2 g-1)
      and high porosity (0.49 cm3 g-1). This carbon was capable of accommodating up to
      60% by weight of sulfur, infiltrated by the disulphide method. The C-S composite
      released an initial specific capacity of 915 mAh g-1 in the Li-S cell at a
      current density of 100 mA g-1 with a high retention capacity of 760 mAh g-1 after
      100 cycles and a coulombic efficiency close to 100%. The good performance of the
      composite was also observed under higher current rates (up to 1000 mA g-1). The
      overall electrochemical behaviour of this microporous carbon acting as a sulfur
      host reinforces the possibility of using biomass residues as sustainable sources
      of materials for energy storage.

PMID- 30110893
TI  - Removal of the N-Glycosylation Sequon at Position N116 Located in p27 of the
      Respiratory Syncytial Virus Fusion Protein Elicits Enhanced Antibody Responses
      after DNA Immunization.
AB  - Prevention of severe lower respiratory tract infections in infants caused by the
      human respiratory syncytial virus (hRSV) remains a major public health priority.
      Currently, the major focus of vaccine development relies on the RSV fusion (F)
      protein since it is the main target protein for neutralizing antibodies induced
      by natural infection. The protein conserves 5 N-glycosylation sites, two of which
      are located in the F2 subunit (N27 and N70), one in the F1 subunit (N500) and two
      in the p27 peptide (N116 and N126). To study the influence of the loss of one or
      more N-glycosylation sites on RSV F immunogenicity, BALB/c mice were immunized
      with plasmids encoding RSV F glycomutants. In comparison with F WT DNA immunized
      mice, higher neutralizing titres were observed following immunization with F
      N116Q. Moreover, RSV A2-K-line19F challenge of mice that had been immunized with
      mutant F N116Q DNA was associated with lower RSV RNA levels compared with those
      in challenged WT F DNA immunized animals. Since p27 is assumed to be post
      translationally released after cleavage and thus not present on the mature RSV F
      protein, it remains to be elucidated how deletion of this glycan can contribute
      to enhanced antibody responses and protection upon challenge. These findings
      provide new insights to improve the immunogenicity of RSV F in potential vaccine
      candidates.

PMID- 30110896
TI  - Willingness to Participate in Vaccine-Related Clinical Trials among Older Adults.
AB  - The purpose of this study is to understand among a convenience sample of 400
      adults aged 60 years of age or older (1) reasons for being willing or unwilling
      to participate in a vaccine clinical research study and (2) overall perceptions
      about vaccine clinical research. A cross-sectional study using a sample of older
      adults residing in the metro-Atlanta area and surrounding neighborhoods was
      conducted. The study questionnaire contained 37 questions, including questions
      about socio-demographics and perceptions about clinical trial processes.
      Statistical analysis was conducted using logistic regression. The adjusted
      modeling results indicated that sex, distance to research clinic, and being
      informed about the research findings played a role in the likelihood of an
      elderly person participating in a vaccine study. Males were more likely to
      participate in clinical trials as compared to females (OR: 2.486; CI: 1.042
      5.934). Most participants were willing to travel up to 25 miles from the research
      clinic. Of the respondents, 45% were unlikely to participate if the results of
      the current trial are not shared. Improving access to clinical trials in terms of
      distance traveled and ensuring streamlined processes to inform participants about
      the results of the trial in the future would increase willingness to participate
      in vaccine clinical trials. The survey could serve as a useful tool for
      conducting vaccine studies and other clinical trials by understanding the
      barriers specific to the elderly.

PMID- 30110898
TI  - Predictors of Problematic Smartphone Use: An Examination of the Integrative
      Pathways Model and the Role of Age, Gender, Impulsiveness, Excessive Reassurance
      Seeking, Extraversion, and Depression.
AB  - Background: The progression of mobile phone technology has led to the development
      of multi-functional smartphones providing access to features such as social
      media, e-mail, and videos alongside the basic functions of a mobile phone.
      Increasing amounts of research has explored the potential addictive nature of
      smartphones to develop a theoretical framework that describes personality factors
      related to problematic use. The present study examined the Integrative Pathways
      Model and the effect of age, gender, impulsiveness, excessive reassurance
      seeking, extraversion, and depression on problematic smartphone use. Method: A
      total of 147 smartphone users (mean age = 30.96, SD = 12.97, 69.4% female)
      completed an online survey comprising of measures of problematic smartphone use,
      excessive reassurance seeking, extraversion, depression, and impulsiveness.
      Results: Age, impulsiveness, excessive reassurance seeking, and depression were
      all significantly related to problematic smartphone use, however extraversion was
      not significantly related. Furthermore, age and impulsiveness were significant
      independent predictors of problematic smartphone use. No gender differences were
      found. Conclusions: The findings presented several factors that predict
      problematic smartphone use, implications and suggestions for future research are
      discussed.

PMID- 30110897
TI  - Single-Strand Break End Resection in Genome Integrity: Mechanism and Regulation
      by APE2.
AB  - DNA single-strand breaks (SSBs) occur more than 10,000 times per mammalian cell
      each day, representing the most common type of DNA damage. Unrepaired SSBs
      compromise DNA replication and transcription programs, leading to genome
      instability. Unrepaired SSBs are associated with diseases such as cancer and
      neurodegenerative disorders. Although canonical SSB repair pathway is activated
      to repair most SSBs, it remains unclear whether and how unrepaired SSBs are
      sensed and signaled. In this review, we propose a new concept of SSB end
      resection for genome integrity. We propose a four-step mechanism of SSB end
      resection: SSB end sensing and processing, as well as initiation, continuation,
      and termination of SSB end resection. We also compare different mechanisms of SSB
      end resection and DSB end resection in DNA repair and DNA damage response (DDR)
      pathways. We further discuss how SSB end resection contributes to SSB signaling
      and repair. We focus on the mechanism and regulation by APE2 in SSB end resection
      in genome integrity. Finally, we identify areas of future study that may help us
      gain further mechanistic insight into the process of SSB end resection. Overall,
      this review provides the first comprehensive perspective on SSB end resection in
      genome integrity.

PMID- 30110899
TI  - Biosensors for the Detection of Interaction between Legionella pneumophila
      Collagen-Like Protein and Glycosaminoglycans.
AB  - The adhesin Legionella collagen-like (Lcl) protein can bind to extracellular
      matrix components and mediate the binding of Legionella pneumophila to host
      cells. In this study, electrochemical impedance spectroscopy (EIS) and surface
      plasmon resonance (SPR)-based biosensors were employed to characterize these
      interactions between glycosaminoglycans (GAGs) and the adhesin Lcl protein.
      Fucoidan displayed a high affinity (KD 18 nM) for Lcl protein. Chondroitin
      sulfate A and dermatan sulfate differ in the position of a carboxyl group
      replacing D-glucuronate with D-iduronate. Our results indicated that the presence
      of D-iduronate in dermatan sulfate strongly hindered its interaction with Lcl.
      These biophysical studies provided valuable information in our understanding of
      adhesin-ligand interactions related to Legionella pneumophila infections.

PMID- 30110900
TI  - Characteristics of Biologically Active Compounds in Cornelian Cherry Meads.
AB  - In this study, we investigated the effect of Cornelian cherry cultivars differing
      in fruit color ("Yantaryi"-yellow fruits, "Koralovyi"-coral fruits, "Podolski"
      red fruits) on physicochemical characteristics, antioxidative properties, and
      contents of iridoids and polyphenols in meads with the addition of juices made of
      their fruits. "Trojniak" type meads (1:2 honey to water volume) were manufactured
      from multifloral honey, to which Cornelian cherry fruit juice was added before
      fermentation. Concentrations of individual iridoids and polyphenols were
      determined using HPLC analysis with a thermostat refractometric detector, model
      RID-10A. The total polyphenol content was determined based on testing with Folin
      Ciocalteu (F-C) reagent, whereas the antioxidative properties were determined
      using DPPH* (2,2-Diphenyl-2-picryl-hydrazyl), ABTS*+ (2,2'-Azino-bis(3-ethylbenzo
      thiazoline-6-sulfonic acid), and FRAP (ferric reducing antioxidant power) assays.
      Cultivar of Cornelian cherry fruits influenced both the antioxidative properties
      and the concentrations of polyphenols and iridoids. The highest concentration of
      total polyphenols (F-C), accounting for 898.7 mg gallic acid (GAE)/L, was
      determined in the mead with juice made of red fruits; this mead was also
      characterized by the strongest antioxidative capabilities measured with ABTS*+
      and FRAP assays. Among the iridoids determined in the Cornelian cherry meads,
      loganic acid was found to prevail and its highest concentration, reaching 77.8 mg
      loganic acid (LA)/L mead, was determined in the mead with the coral-fruit juice.
      Study results indicate that Cornelian cherry meads have a high content of
      biologically active iridoids and phenolic acids which display valuable
      antioxidative properties.

PMID- 30110902
TI  - Micro-CT to Document the Coffee Bean Weevil, Araecerus fasciculatus (Coleoptera:
      Anthribidae), Inside Field-Collected Coffee Berries (Coffea canephora).
AB  - The coffee bean weevil, Araecerus fasciculatus (De Geer) (Coleoptera:
      Anthribidae), is a cosmopolitan insect with >100 hosts, and has been reported as
      a pest of stored coffee. During a study involving the coffee berry borer, we
      observed coffee bean weevils emerging from field-collected coffee berries and
      used micro-computerized tomography (micro-CT) scans to observe the insect inside
      the berry. Two eggs had eclosed inside the berry, resulting in observations of a
      newly eclosed adult beetle and a 5th instar larva, each feeding on one of the two
      seeds. This is the first time since 1775, when the insect was first described,
      that the insect has been observed inside a coffee berry.

PMID- 30110901
TI  - Designing Lubricating Properties of Vegetable Base Oils.
AB  - Lubricants that are based on renewable raw materials have drawn increased
      attention in various applications, especially those related to the food industry.
      Due to the high requirements of environmental protection, there is a need to
      develop biodegradable base oils that are environmentally friendly and do not
      contain harmful components. The objective of the research was to obtain a base
      oil with a certain viscosity and certain desired lubricating properties. Base
      oils were obtained from Crambe abyssinica oil by means of blending with synthetic
      oil and oxidation. The oxidation processes were carried out in the presence of N
      hydroxyphthalimide with or without CO2 as a solvent. As a final result of this
      study, oil bases meeting the viscosity requirements and showing suitable
      lubricating properties were obtained. The Raman spectra of the obtained oils were
      evaluated.

PMID- 30110903
TI  - Vape Club: Exploring Non-Profit Regulatory Models for the Supply of Vaporised
      Nicotine Products.
AB  - Vaporised nicotine products (VNPs) that are not approved as therapeutic goods are
      banned in some countries, including Australia, Singapore, and Thailand. We
      reviewed two non-profit regulatory options, private clubs and the Australian
      Therapeutic Goods Administration Special Access Scheme (SAS) that have been
      applied to other controlled substances (such as cannabis) as a potential model
      for regulating VNPs as an alternative to prohibition. The legal status of private
      cannabis clubs varies between the United States, Canada, Belgium, Spain, and
      Uruguay. Legal frameworks exist for cannabis clubs in some countries, but most
      operate in a legal grey area. Kava social clubs existed in the Northern
      Territory, Australia, until the federal government banned importation of kava.
      Access to medical cannabis in Australia is allowed as an unapproved therapeutic
      good via the SAS. In Australia, the SAS Category C appears to be the most
      feasible option to widen access to VNPs, but it may have limited acceptability to
      vapers and smokers. The private club model would require new legislation but
      could be potentially more acceptable if clubs were permitted to operate outside a
      medical framework. Consumer and regulator support for these models is currently
      unknown. Without similar restrictions applied to smoked tobacco products, these
      models may have only a limited impact on smoking prevalence. Further research
      could explore whether these models could be options for regulating smoked tobacco
      products.

PMID- 30110904
TI  - Assessment of the Potential Economic Impact of the Use of AM Technologies in the
      Cost Levels of Manufacturing and Stocking of Spare Part Products.
AB  - Additive manufacturing (AM) technologies are appropriate manufacturing
      technologies to produce low rotation products of high added value. Products in
      the spare parts business usually have discontinuous demand levels of reduced
      numbers of parts. Indeed, spare parts inventories handle myriad of products that
      require big immobilized investments while having an intrinsic risk of no-use (for
      example due to obsolescence or spoilage). Based on these issues, the present work
      analyses the fundamental cost factors in a real case study of a company dedicated
      to the supply of spare parts for fluid conduction systems. Real inventory data is
      assessed to determine the product taxonomy and its associated costs. A
      representative product of the stock is analyzed in detail on original
      manufacturing costs, in AM costs and then redesigned with topological
      optimization to reduce the AM cost levels (via design for additive
      manufacturing). A general equation for cost assessment is formulated. Given the
      specific data collected from the company, the parameters in this general equation
      are calculated. Finally, the general equation and the product cost reduction
      achieved are used to explore the potential economic impact of the use of AM
      technologies in the cost levels of manufacturing and stocking of spare part
      products.

PMID- 30110905
TI  - Isolation and Purification of Galloyl, Caffeoyl, and Hexahydroxydiphenoyl Esters
      of Glucoses from Balanophora simaoensis by High-Speed Countercurrent
      Chromatography and Their Antioxidant Activities In Vitro.
AB  - High-speed counter-current chromatography was used to separate and purify
      galloyl, caffeoyl, and hexahydroxydiphenoyl esters of glucoses from the aerial
      parts of the parasitic plant Balanophora simaoensis for the first time using n
      hexane-ethyl acetate-methanol-water (1:2:1:2, v/v) as the optimum solvent system.
      Accordingly, 1-O-(E)-caffeoyl-3-O-galloyl-beta-d-glucopyranose (I, 12.5 mg), 1-O
      (E)-caffeoyl-3-O-galloyl-4,6-(S)-hexahydroxydiphenoyl-beta-d-glucopyranose (II,
      27.2 mg), and 1-O-(E)-caffeoyl-4,6-(S)-hexahydroxydiphenoyl-beta-d-glucopyranose
      (III, 52.8 mg) with 98.0%, 98.5%, and 98.7% purities, respectively, were purified
      from 210 mg crude extract of B. simaoensis in a one-step separation. The
      structures of the glucose esters were identified by electrospray ionization mass
      spectrometry (ESI-MS) and nuclear magnetic resonance spectra (NMR). Their
      antioxidant activities were evaluated by measuring their inhibition activity on
      liver microsomal lipid peroxidation induced by the Fe2+-Cys system in vitro.
      Compounds I-III showed significant antioxidant activities with IC50 values
      ranging from 2.51 to 6.68 MUm, respectively.

PMID- 30110907
TI  - In Vivo Irradiation of Mice Induces Activation of Dendritic Cells.
AB  - It is becoming clear that ionizing radiation positively influences certain immune
      parameters, which opens the possibility for combining radio- and immunotherapies
      in cancer treatment. The presence of functionally competent dendritic cells (DCs)
      is crucial in mounting a successful antitumor immune response. While it has been
      shown that DCs are relatively radioresistant, few and contradictory data are
      available on how ionizing radiation alters the functional integrity of these
      cells. Therefore, our objective was to investigate the effect of whole-body
      irradiation on the function of splenic DCs. C57Bl/6 mice were irradiated with
      0.1, 0.25, and 2 Gy X-rays and changes in the phenotype of splenic DCs were
      compared to unirradiated controls. An increase was seen in DC surface markers
      influencing DC-T cell interactions. In vivo cytokine production was determined by
      direct intracellular cytokine staining. Irradiation with 2 Gy induced a 1.6-fold
      increase in IL-1alpha production, while the combination of irradiation and
      lipopolysaccharide (LPS) treatment induced a 3.9-fold increase, indicating a
      strong synergism between irradiation and LPS stimulation. Interaction of DCs with
      effector and regulatory T cells was investigated in a mixed lymphocyte reaction.
      While DCs from control animals induced stronger proliferation of regulatory T
      cells, DCs from animals irradiated with 2 Gy induced stronger proliferation of
      effector T cells. Antigen uptake and presentation was investigated by measuring
      the capacity of DCs to internalize and present ovalbumine (OVA)-derived peptides
      on their major histocompatibility complex (MHCI) molecules. Irradiation with 2 Gy
      did not influence antigen uptake or presentation, while low doses stimulated
      antigen uptake and reduced the level of antigen presentation. In conclusion, high
      dose in vivo irradiation induced increased expression of T cell costimulatory
      markers, enhanced production of proinflammatory cytokines and a stronger
      stimulation of effector T cell proliferation than that of regulatory T cells.
      However, it did not influence DC antigen uptake or presentation. On the other
      hand, low-dose irradiation increased antigen uptake and lowered antigen
      presentation of DCs, indicating that low- and high-dose irradiation act on
      different pathways in DCs.

PMID- 30110906
TI  - Omics Approaches for Engineering Wheat Production under Abiotic Stresses.
AB  - Abiotic stresses greatly influenced wheat productivity executed by environmental
      factors such as drought, salt, water submergence and heavy metals. The effective
      management at the molecular level is mandatory for a thorough understanding of
      plant response to abiotic stress. Understanding the molecular mechanism of stress
      tolerance is complex and requires information at the omic level. In the areas of
      genomics, transcriptomics and proteomics enormous progress has been made in the
      omics field. The rising field of ionomics is also being utilized for examining
      abiotic stress resilience in wheat. Omic approaches produce a huge amount of data
      and sufficient developments in computational tools have been accomplished for
      efficient analysis. However, the integration of omic-scale information to address
      complex genetics and physiological questions is still a challenge. Though, the
      incorporation of omic-scale data to address complex genetic qualities and
      physiological inquiries is as yet a challenge. In this review, we have reported
      advances in omic tools in the perspective of conventional and present day
      approaches being utilized to dismember abiotic stress tolerance in wheat.
      Attention was given to methodologies, for example, quantitative trait loci (QTL),
      genome-wide association studies (GWAS) and genomic selection (GS). Comparative
      genomics and candidate genes methodologies are additionally talked about
      considering the identification of potential genomic loci, genes and biochemical
      pathways engaged with stress resilience in wheat. This review additionally gives
      an extensive list of accessible online omic assets for wheat and its effective
      use. We have additionally addressed the significance of genomics in the
      integrated approach and perceived high-throughput multi-dimensional phenotyping
      as a significant restricting component for the enhancement of abiotic stress
      resistance in wheat.

PMID- 30110908
TI  - Osteogenic Potential of Graphene in Bone Tissue Engineering Scaffolds.
AB  - Scaffolds are physical substrates for cell attachments, proliferation, and
      differentiation, ultimately leading to tissue regeneration. Current literature
      validates tissue engineering as an emerging tool for bone regeneration. Three
      dimensionally printed natural and synthetic biomaterials have been traditionally
      used for tissue engineering. In recent times, graphene and its derivatives are
      potentially employed for constructing bone tissue engineering scaffolds because
      of their osteogenic and regenerative properties. Graphene is a synthetic atomic
      layer of graphite with SP2 bonded carbon atoms that are arranged in a honeycomb
      lattice structure. Graphene can be combined with natural and synthetic
      biomaterials to enhance the osteogenic potential and mechanical strength of
      tissue engineering scaffolds. The objective of this review is to focus on the
      most recent studies that attempted to explore the salient features of graphene
      and its derivatives. Perhaps, a thorough understanding of the material science
      can potentiate researchers to use this novel substitute to enhance the osteogenic
      and biological properties of scaffold materials that are routinely used for bone
      tissue engineering.

PMID- 30110909
TI  - Decellularized Tissue for Muscle Regeneration.
AB  - Several acquired or congenital pathological conditions can affect skeletal muscle
      leading to volumetric muscle loss (VML), i.e., an irreversible loss of muscle
      mass and function. Decellularized tissues are natural scaffolds derived from
      tissues or organs, in which the cellular and nuclear contents are eliminated, but
      the tridimensional (3D) structure and composition of the extracellular matrix
      (ECM) are preserved. Such scaffolds retain biological activity, are biocompatible
      and do not show immune rejection upon allogeneic or xenogeneic transplantation.
      An increase number of reports suggest that decellularized tissues/organs are
      promising candidates for clinical application in patients affected by VML. Here
      we explore the different strategies used to generate decellularized matrix and
      their therapeutic outcome when applied to treat VML conditions, both in patients
      and in animal models. The wide variety of VML models, source of tissue and
      methods of decellularization have led to discrepant results. Our review study
      evaluates the biological and clinical significance of reported studies, with the
      final aim to clarify the main aspects that should be taken into consideration for
      the future application of decellularized tissues in the treatment of VML
      conditions.

PMID- 30110912
TI  - Understanding the Thickness Effect on the Tensile Strength Property of
      Dyneema(r)HB26 Laminates.
AB  - In this study, an experimental and numerical investigation is presented on the
      effect of thickness and test rate within the pseudo static regime on the tensile
      properties of Dyneema(r)HB26 laminates. A detailed experimental presentation on
      the tensile testing of different thickness is presented and highlights the
      commonly seen observation that the tensile strength of a laminate reduces as a
      function of the specimen thickness. To understand these experimental
      observations, a constitutive material model of the individual macro fibril is
      developed and applied to modelling the fibre and upscaling to the laminate. The
      modelling strategy is implemented into ls-dyna and used to perform a parameter
      study on the specimen geometries used in the experimental study. The model
      assumes that the fibril strength is a function of the amorphous volume within the
      fibre and hence fibril. It can be observed that the experimental behaviour can be
      simulated by modelling the interface between laminate plies and the fibril, and
      hence fibre failure. The weak interfaces from the fibril to the laminate scale
      make the testing of fibres and laminates very difficult. Hence, it is proposed
      that the intrinsic fibril strength should be used as a measure of strength, and
      the fundamental strength is determined through numerical studies.

PMID- 30110911
TI  - Isolation and Structural Characterization of Bioactive Molecules on Prostate
      Cancer from Mayan Traditional Medicinal Plants.
AB  - Prostate cancer is the most common cancer in men around the world. It is a
      complex and heterogeneous disease in which androgens and their receptors play a
      crucial role in the progression and development. The current treatment for
      prostate cancer is a combination of surgery, hormone therapy, radiation and
      chemotherapy. Therapeutic agents commonly used in the clinic include steroidal
      and non-steroidal anti-androgens, such as cyproterone acetate, bicalutamide and
      enzalutamide. These few agents have multiple adverse effects and are not 100%
      effective. Several plant compounds and mixtures, including grape seed polyphenol
      extracts, lycopene and tomato preparations, soy isoflavones, and green tea
      extracts, have been shown to be effective against prostate cancer cell growth. In
      vivo activity of some isolated compounds like capsaicin and curcumin was reported
      in prostate cancer murine models. We prepared a library of plant extracts from
      traditional Mayan medicine. These plants were selected for their use in the
      contemporaneous Mayan communities for the treatment of different diseases. The
      extracts were assessed in a phenotypic screening using LNCaP prostate cancer
      androgen sensitive cell line, with a fixed dose of 25 MUg/mL. MTT assay
      identified seven out of ten plants with interesting anti-neoplastic activity.
      Extracts from these plants were subjected to a bioguided fractionation to study
      their major components. We identified three compounds with anti-neoplastic
      effects against LNCaP cells, one of which shows selectivity for neoplastic
      compared to benign cells.

PMID- 30110910
TI  - Targeting the Multidrug Transporter Ptch1 Potentiates Chemotherapy Efficiency.
AB  - One of the crucial challenges in the clinical management of cancer is resistance
      to chemotherapeutics. Multidrug resistance (MDR) has been intensively studied,
      and one of the most prominent mechanisms underlying MDR is overexpression of
      adenosine triphosphate (ATP)-binding cassette (ABC) transporters. Despite
      research efforts to develop compounds that inhibit the efflux activity of ABC
      transporters and thereby increase classical chemotherapy efficacy, to date, the
      Food and Drug Administration (FDA) has not approved the use of any ABC
      transporter inhibitors due to toxicity issues. Hedgehog signaling is aberrantly
      activated in many cancers, and has been shown to be involved in chemotherapy
      resistance. Recent studies showed that the Hedgehog receptor Ptch1, which is over
      expressed in many recurrent and metastatic cancers, is a multidrug transporter
      and it contributes to the efflux of chemotherapeutic agents such as doxorubicin,
      and to chemotherapy resistance. Remarkably, Ptch1 uses the proton motive force to
      efflux drugs, in contrast to ABC transporters, which use ATP hydrolysis. Indeed,
      the "reversed pH gradient" that characterizes cancer cells, allows Ptch1 to
      function as an efflux pump specifically in cancer cells. This makes Ptch1 a
      particularly attractive therapeutic target for cancers expressing Ptch1, such as
      lung, breast, prostate, ovary, colon, brain, adrenocortical carcinoma, and
      melanoma. Screening of chemical libraries have identified several molecules that
      are able to enhance the cytotoxic effect of different chemotherapeutic agents by
      inhibiting Ptch1 drug efflux activity in different cancer cell lines that
      endogenously over-express Ptch1. In vivo proof of concept has been performed in
      mice where combining one of these compounds with doxorubicin prevented the
      development of xenografted adrenocortical carcinoma tumors more efficiently than
      doxorubicin alone, and without obvious undesirable side effects. Therefore, the
      use of a Ptch1 drug efflux inhibitor in combination with classical or targeted
      therapy could be a promising therapeutic option for Ptch1-expressing cancers.

PMID- 30110913
TI  - Pilot Study of Immunoblots with Recombinant Borrelia burgdorferi Antigens for
      Laboratory Diagnosis of Lyme Disease.
AB  - Accurate laboratory diagnosis of Lyme disease (Lyme borreliosis), caused by the
      spirochete Borrelia burgdorferi (BB), is difficult and yet important to prevent
      serious disease. The US Centers for Disease Control and Prevention (CDC)
      presently recommends a screening test for serum antibodies followed by
      confirmation with a more specific Western blot (WB) test to detect IgG and IgM
      antibodies against antigens in whole cell lysates of BB. Borrelia species related
      to BB cause tick-borne relapsing fever (TBRF). TBRF is increasingly recognized as
      a health problem in the US and occurs in areas where Lyme disease is prevalent.
      The two groups of Borrelia share related antigens. We have developed a modified
      WB procedure termed the Lyme immunoblots (IBs) using recombinant antigens from
      common strains and species of the BB sensu lato complex for serological diagnosis
      of Lyme disease. A reference collection of 178 sera from 26 with and 152 patients
      without Lyme disease were assessed by WB and IB in a blinded manner using either
      criteria for positive antibody reactions recommended by the CDC or criteria
      developed in-house. The sensitivity, specificity, positive and negative
      predictive values obtained with the reference sera suggest that the Lyme IB is
      superior to the Lyme WB for detection of specific antibodies in Lyme disease. The
      Lyme IB showed no significant reaction with rabbit antisera produced against two
      Borrelia species causing TBRF in the US, suggesting that the Lyme IB may be also
      useful for excluding TBRF.

PMID- 30110915
TI  - Synthesis of New 5-Aryl-benzo[f][1,7]naphthyridines via a Cascade Process (Ugi
      3CR/Intramolecular Aza-Diels-Alder Cycloaddition)/Aromatization.
AB  - A series of eight new 5-aryl-benzo[f][1,7]naphthyridines were synthesized in 17
      to 64% overall yields via an improved MW-assisted cascade-like one pot process
      (Ugi-three component reaction/intramolecular aza-Diels-Alder cycloaddition)
      coupled to an aromatization process from tri-functional dienophile-containing
      ester-anilines, substituted benzaldehydes and the chain-ring tautomerizable 2
      isocyano-1-morpholino-3-phenylpropan-1-one as starting reagents, under mild
      conditions. The doubly activated dienophile and the aza-diene functionalities of
      the eight new Ugi-adducts were exploited to perform an in situ aza-Diels-Alder
      cycloaddition/aromatization (dehydration/oxidation) process, toward the complex
      polysubstituted 5-aryl-polyheterocycles, which could be taken as starting point
      for further SAR studies because the benzo[f][1,7]naphthyridine is the core of
      various bioactive products. It is relevant to emphasize that the synthesis or
      isolation of benzo[f][1,7]naphthyridines containing a substituted aromatic ring
      in the C-5 position, has not been published before.

PMID- 30110914
TI  - Evaluation of Amino-Functional Polyester Dendrimers Based on Bis-MPA as Nonviral
      Vectors for siRNA Delivery.
AB  - Herein, we present the first evaluation of cationic dendrimers based on 2,2
      bis(methylol)propionic acid (bis-MPA) as nonviral vectors for transfection of
      short interfering RNA (siRNA) in cell cultures. The study encompassed dendrimers
      of generation one to four (G1-G4), modified to bear 6-48 amino end-groups, where
      the G2-G4 proved to be capable of siRNA complexation and protection against RNase
      mediated degradation. The dendrimers were nontoxic to astrocytes, glioma (C6),
      and glioblastoma (U87), while G3 and G4 exhibited concentration dependent
      toxicity towards primary neurons. The G2 showed no toxicity to primary neurons at
      any of the tested concentrations. Fluorescence microscopy experiments suggested
      that the dendrimers are highly efficient at endo-lysosomal escape since
      fluorescently labeled dendrimers were localized specifically in mitochondria, and
      diffuse cytosolic distribution of fluorescent siRNA complexed by dendrimers was
      observed. This is a desired feature for intracellular drug delivery, since the
      endocytic pathway otherwise transfers the drugs into lysosomes where they can be
      degraded without reaching their intended target. siRNA-transfection was
      successful in C6 and U87 cell lines using the G3 and G4 dendrimers followed by a
      decrease of approximately 20% of target protein p42-MAPK expression.

PMID- 30110917
TI  - Contingency Contracts for Weight Gain of Patients with Anorexia Nervosa in
      Inpatient Therapy: Practice Styles of Specialized Centers.
AB  - The treatment of patients with anorexia nervosa (AN) is often challenging, due to
      a high degree of ambivalence towards recovery and weight gain these patients
      often express. One part of the multimodal treatment is the utilization of
      treatment contracts (i.e., contingency contracts) that aim to motivate patients
      to gain weight by applying positive and negative consequences for the (non
      )achievement of weight goals. The main aim of this study is to assess and analyze
      current standards of contingency contracts' utilization in German eating disorder
      centers. n = 76 mental health professionals of twelve specialized university
      centers in Germany that are currently or were formerly treating patients with AN
      in an inpatient setting participated. Most experts use contingency contracts in
      their clinic with weekly weight goals ranging between 500 and 700 g. Overall
      effectiveness and significance of contingency contracts for the inpatient
      treatment of patients with AN was rated high. Typical characteristics of a
      contingency contract in specialized German university hospital centers, such as
      the most frequent consequences, are described. The survey results assist the
      planning of further studies aiming to improve the multimodal treatment of
      patients with AN. For clinical practice, using external motivators such as
      contingency contracts as well as targeting internal motivation (e.g., by using
      motivational interviewing) is proposed.

PMID- 30110916
TI  - HJH-1, a Broad-Spectrum Antimicrobial Activity and Low Cytotoxicity Antimicrobial
      Peptide.
AB  - With the overuse of antibiotics, multidrug-resistant bacteria pose a significant
      threat to human health. Antimicrobial peptides (AMPs) are a promising alternative
      to conventional antibiotics. This study examines the antimicrobial and membrane
      activity of HJH-1, a cationic peptide derived from the hemoglobin alpha-subunit
      of bovine erythrocytes P3. HJH-1 shows potent antimicrobial activity against
      different bacterial species associated with infection and causes weaker hemolysis
      of erythrocytes, at least five times the minimum inhibitory concentration (MIC).
      HJH-1 has good stability to tolerance temperature, pH value, and ionic strength.
      The anionic membrane potential probe bis-(1,3-dibutylbarbituric acid) trimethine
      oxonol [DiBAC4(3)] and propidium iodide are used as indicators of membrane
      integrity. In the presence of HJH-1 (1* MIC), Escherichiacoli membranes rapidly
      depolarise, whereas red blood cells show gradual hyperpolarisation. Scanning
      electron microscopy and transmission electron micrographs show that HJH-1 (1*
      MIC) damaged the membranes of Escherichia coli, Staphylococcus aureus, and
      Candida albicans. In conclusion, HJH-1 damages the integrity of the bacterial
      membrane, preventing the growth of bacteria. HJH-1 has broad-spectrum
      antibacterial activity, and these activities are performed by changing the normal
      cell transmembrane potential and disrupting the integrity of the bacterial
      membrane.

PMID- 30110918
TI  - Where Did They Come from-Multi-Drug Resistant Pathogenic Escherichia coli in a
      Cemetery Environment?
AB  - Human burial in cemeteries facilitates the decomposition of corpses without
      posing a public health danger. However, the role of cemeteries as potential
      environmental reservoirs of drug-resistant pathogens has not been studied. Thus,
      we investigated cemeteries as potential environmental reservoirs of multi-drug
      resistant (MDR) pathogenic Escherichia coli. E. coli isolates were obtained from
      water samples (collected from surface water bodies and boreholes in three
      cemeteries) after isolation using the Colilert(r) 18 system. Pathogenic
      potentials of the isolates were investigated using real-time polymerase chain
      reactions targeting seven virulence genes (VGs) pertaining to six E. coli
      pathotypes. The resistance of isolates to eight antibiotics was tested using the
      Kirby-Bauer disc diffusion method. The mean E. coli concentrations varied from <1
      most probable number (MPN)/100 mL to 2419.6 MPN/100 mL with 48% of 100 isolates
      being positive for at least one of the VGs tested. Furthermore, 87% of the
      isolates were resistant to at least one of the antibiotics tested, while 72% of
      the isolates displayed multi-drug resistance. Half of the MDR isolates harboured
      a VG. These results suggest that cemeteries are potential reservoirs of MDR
      pathogenic E. coli, originating from surrounding informal settlements, which
      could contaminate groundwater if the cemeteries are in areas with shallow
      aquifers.

PMID- 30110919
TI  - A Novel Sensitive Cell-Based Immunoenzymatic Assay for Palytoxin Quantitation in
      Mussels.
AB  - The marine algal toxin palytoxin (PLTX) and its analogues are some of the most
      toxic marine compounds. Their accumulation in edible marine organisms and
      entrance into the food chain represent their main concerns for human health.
      Indeed, several fatal human poisonings attributed to these compounds have been
      recorded in tropical and subtropical areas. Due to the increasing occurrence of
      PLTX in temperate areas such as the Mediterranean Sea, the European Food Safety
      Authority (EFSA) has suggested a maximum limit of 30 ug PLTX/kg in shellfish
      meat, and has recommended the development of rapid, specific, and sensitive
      methods for detection and quantitation of PLTX in seafood. Thus, a novel,
      sensitive cell-based ELISA was developed and characterized for PLTX quantitation
      in mussels. The estimated limits of detection (LOD) and quantitation (LOQ) were
      1.2 * 10-11 M (32.2 pg/mL) and 2.8 * 10-11 M (75.0 pg/mL), respectively, with
      good accuracy (bias = 2.5%) and repeatability (15% and 9% interday and intraday
      relative standard deviation of repeatability (RSDr), respectively). Minimal
      interference of 80% aqueous methanol extract allows PLTX quantitation in mussels
      at concentrations lower than the maximum limit suggested by EFSA, with an LOQ of
      9.1 ug PLTX equivalent/kg mussel meat. Given its high sensitivity and
      specificity, the cell-based ELISA should be considered a suitable method for PLTX
      quantitation.

PMID- 30110921
TI  - Model for the Correlation between Anodic Dissolution Resistance and
      Crystallographic Texture in Pipeline Steels.
AB  - This paper presents a novel physical-mathematical model to describe the
      relationship between the crystallographic texture and corrosion behavior of
      American petroleum institute (API) 5L steels. Symmetric spherical harmonic
      functions were used to estimate the material's corrosion resistance from
      crystallographic texture measurements. The predictions of the average corrosion
      resistance index made from the crystallographic texture were in good agreement
      with those obtained from potentiodynamic polarization and electrochemical
      impedance spectroscopy measurements for the studied steels. This agreement
      validates the capacity of this model and opens the possibility of applying it as
      a novel criterion for materials selection and design stages to combat corrosion
      problems.

PMID- 30110920
TI  - Evening Primrose (Oenothera biennis) Biological Activity Dependent on Chemical
      Composition.
AB  - Evening primrose (Oenothera L.) is a plant belonging to the family Onagraceae, in
      which the most numerous species is Oenothera biennis. Some plants belonging to
      the genus Oenothera L. are characterized by biological activity. Therefore,
      studies were conducted to determine the dependence of biological activity on the
      chemical composition of various parts of the evening primrose, mainly leaves,
      stems, and seeds. Common components of all parts of the Oenothera biennis plants
      are fatty acids, phenolic acids, and flavonoids. In contrast, primrose seeds also
      contain proteins, carbohydrates, minerals, and vitamins. Therefore, it is
      believed that the most interesting sources of biologically active compounds are
      the seeds and, above all, evening primrose seed oil. This oil contains mainly
      aliphatic alcohols, fatty acids, sterols, and polyphenols. Evening primrose oil
      (EPO) is extremely high in linoleic acid (LA) (70-74%) and gamma-linolenic acid
      (GLA) (8-10%), which may contribute to the proper functioning of human tissues
      because they are precursors of anti-inflammatory eicosanoids. EPO supplementation
      results in an increase in plasma levels of gamma-linolenic acid and its
      metabolite dihomo-gamma-linolenic acid (DGLA). This compound is oxidized by
      lipoxygenase (15-LOX) to 15-hydroxyeicosatrienoic acid (15-HETrE) or, under the
      influence of cyclooxygenase (COX), DGLA is metabolized to series 1
      prostaglandins. These compounds have anti-inflammatory and anti-proliferative
      properties. Furthermore, 15-HETrE blocks the conversion of arachidonic acid (AA)
      to leukotriene A4 (LTA4) by direct inhibition of 5-LOX. In addition, gamma
      linolenic acid suppresses inflammation mediators such as interleukin 1beta (IL
      1beta), interleukin 6 (IL-6), and cytokine - tumor necrosis factor alpha (TNF
      alpha). The beneficial effects of EPO have been demonstrated in the case of
      atopic dermatitis, psoriasis, Sjogren's syndrome, asthma, and anti-cancer
      therapy.

PMID- 30110922
TI  - Lethal and Sublethal Effects of Three Microbial Biocontrol Agents on Spodoptera
      litura and Its Natural Predator Rhynocoris kumarii.
AB  - Entomopathogenic microbes such as Spodoptera litura nucleopolyhedrovirus
      (SpltNPV), Metarhizium anisopliae, and Pseudomonas fluorescens are biological
      agents used for the control of multiple arthropod pests. The objective of this
      study was to assess their effects on the biological parameters of Spodoptera
      litura (Lepidoptera: Noctuidae) larvae, and its natural reduviid predator
      Rhynocoris kumarii (Hemiptera: Reduviidae) under laboratory conditions. Results
      suggested that P. fluorescens reduced the food consumption index, relative growth
      rate, approximate digestibility, the efficiency of conversion of ingested food,
      and the efficiency of conversion of digested food of S. litura third instar
      larvae compared to prey infected with M. anisopliae and SpltNPV. Both SpltNPV and
      M. anisopliae caused similar mortality of S. litura life stages after 96 h of
      observation. To observe the effect of an infected prey diet on predator behavior,
      infected S. litura larvae were offered to the third, fourth, and fifth instar
      nymphs of R. kumarii, and their prey handling time, predation rate
      (number/day/predator), developmental period, and the survival rate was recorded.
      When the life stages of R. kumarii were offered entomopathogen-infected S. litura
      larvae, their predation rate was comparable to or higher than the untreated
      control. The juvenile predator, after feeding on P. fluorescens-infected S.
      litura larvae, had a significantly longer developmental period (2-4 days)
      compared to those fed on larvae infected with other microbial control agents.
      However, feeding on P. fluorescens alone did not affect the predator nymphal
      survival rate or the adult sex ratio. Although three entomopathogens had some
      degree of effect on the biological parameters of R. kumarii, the outcome of this
      study suggests that integration of reduviids with the tested entomopathogens are
      a compatible and potentially effective strategy for the management of S. litura
      populations. However promising, this combined strategy needs to be tested under
      field conditions to confirm the laboratory findings.

PMID- 30110924
TI  - Ventriculoperitoneal Shunts Equipped with On-Off Valves for Intraventricular
      Therapies in Patients with Communicating Hydrocephalus due to Leptomeningeal
      Metastases.
AB  - Ventriculoperitoneal shunts equipped with a reservoir and a valve to manually
      switch off the shunt function can be used for intraventricular injections of
      therapeutics in patients suffering from a communicating hydrocephalus caused by
      leptomeningeal metastases. These shunt devices avoid the risk of injecting
      therapeutics through the distal leg of the shunt system into the intraperitoneal
      space, which may cause toxicity. Furthermore, regular intraventricular injections
      of chemotherapeutics help to maintain sufficient concentrations in the
      ventricular space. Therefore, ventriculoperitoneal shunts equipped with an on-off
      valve are a useful tool to reliably inject chemotherapeutics into the ventricles.
      In order to systematically assess feasibility, safety, and efficacy of this
      procedure, we performed a retrospective analysis of all patients with
      leptomeningeal metastases who had received a shunt system at our institution. In
      total, six adult patients had a ventriculoperitoneal shunt equipped with an on
      off valve implanted. Out of these six patients, two patients subsequently
      received intraventricular injections of chemotherapeutics. The configuration of
      the valve setting and the intraventricular injections were easily feasible in the
      setting of a neuro-oncology department. The complication of a shunt leakage
      occurred in one patient following the first intraventricular injection. No extra
      central nervous system (CNS) toxicities were observed. In summary,
      ventriculoperitoneal shunts with on-off valves are useful tools for reliable
      intraventricular administration of therapeutics.

PMID- 30110926
TI  - A Fiber Bragg Grating Based Torsional Vibration Sensor for Rotating Machinery.
AB  - This paper proposes a new type of torsional vibration sensor based on fiber Bragg
      grating (FBG). The sensor has two mass ball optical fiber systems. The optical
      fiber is directly treated as an elastomer and a mass ball is fixed in the middle
      of the fiber in each mass ball fiber system, which is advantageously small,
      lightweight, and has anti-electromagnetic interference properties. The torsional
      vibration signal can be calculated by the four FBGs' wavelength shifts, which are
      caused by mass balls. The difference in the two sets of mass ball optical fiber
      systems achieves anti-horizontal vibration and anti-temperature interference. The
      principle and model of the sensor, as well as numerical analysis and structural
      parameter design, are introduced. The experimental conclusions show that the
      minimum torsional natural frequency of the sensor is 27.35 Hz and the torsional
      vibration measurement sensitivity is 0.3603 pm/(rad/s2).

PMID- 30110925
TI  - Differentiation of Human Tonsil-Derived Mesenchymal Stem Cells into Schwann-Like
      Cells Improves Neuromuscular Function in a Mouse Model of Charcot-Marie-Tooth
      Disease Type 1A.
AB  - Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited motor
      and sensory neuropathy, and is caused by duplication of PMP22, alterations of
      which are a characteristic feature of demyelination. The clinical phenotype of
      CMT1A is determined by the degree of axonal loss, and patients suffer from
      progressive muscle weakness and impaired sensation. Therefore, we investigated
      the potential of Schwann-like cells differentiated from human tonsil-derived stem
      cells (T-MSCs) for use in neuromuscular regeneration in trembler-J (Tr-J) mice, a
      model of CMT1A. After differentiation, we confirmed the increased expression of
      Schwann cell (SC) markers, including glial fibrillary acidic protein (GFAP),
      nerve growth factor receptor (NGFR), S100 calcium-binding protein B (S100B),
      glial cell-derived neurotrophic factor (GDNF), and brain-derived neurotrophic
      factor (BDNF), which suggests the differentiation of T-MSCs into SCs (T-MSC-SCs).
      To test their functional efficiency, the T-MSC-SCs were transplanted into the
      caudal thigh muscle of Tr-J mice. Recipients' improved locomotive activity on a
      rotarod test, and their sciatic function index, which suggests that transplanted
      T-MSC-SCs ameliorated demyelination and atrophy of nerve and muscle in Tr-J mice.
      Histological and molecular analyses showed the possibility of in situ
      remyelination by T-MSC-SCs transplantation. These findings demonstrate that the
      transplantation of heterologous T-MSC-SCs induced neuromuscular regeneration in
      mice and suggest they could be useful for the therapeutic treatment of patients
      with CMT1A disease.

PMID- 30110923
TI  - Current Screening Methodologies in Drug Discovery for Selected Human Diseases.
AB  - The increase of many deadly diseases like infections by multidrug-resistant
      bacteria implies re-inventing the wheel on drug discovery. A better comprehension
      of the metabolisms and regulation of diseases, the increase in knowledge based on
      the study of disease-born microorganisms' genomes, the development of more
      representative disease models and improvement of techniques, technologies, and
      computation applied to biology are advances that will foster drug discovery in
      upcoming years. In this paper, several aspects of current methodologies for drug
      discovery of antibacterial and antifungals, anti-tropical diseases, antibiofilm
      and antiquorum sensing, anticancer and neuroprotectors are considered. For drug
      discovery, two different complementary approaches can be applied: classical
      pharmacology, also known as phenotypic drug discovery, which is the historical
      basis of drug discovery, and reverse pharmacology, also designated target-based
      drug discovery. Screening methods based on phenotypic drug discovery have been
      used to discover new natural products mainly from terrestrial origin. Examples of
      the discovery of marine natural products are provided. A section on future trends
      provides a comprehensive overview on recent advances that will foster the
      pharmaceutical industry.

PMID- 30110927
TI  - The Expanding Role of Radiosurgery for Brain Metastases.
AB  - Stereotactic radiosurgery (SRS) has become increasingly important in the
      management of brain metastases due to improving systemic disease control and
      rising incidence. Initial trials demonstrated SRS with whole-brain radiotherapy
      (WBRT) improved local control rates compared with WBRT alone. Concerns with WBRT
      associated neurocognitive toxicity have contributed to a greater use of SRS
      alone, including for patients with multiple metastases and following surgical
      resection. Molecular information, targeted agents, and immunotherapy have also
      altered the landscape for the management of brain metastases. This review
      summarises current and emerging data on the role of SRS in the management of
      brain metastases.

PMID- 30110928
TI  - Comparative Metagenomic Analysis of Rhizosphere Microbial Community Composition
      and Functional Potentials under Rehmannia glutinosa Consecutive Monoculture.
AB  - Consecutive monoculture of Rehmannia glutinosa, highly valued in traditional
      Chinese medicine, leads to a severe decline in both quality and yield.
      Rhizosphere microbiome was reported to be closely associated with the soil health
      and plant performance. In this study, comparative metagenomics was applied to
      investigate the shifts in rhizosphere microbial structures and functional
      potentials under consecutive monoculture. The results showed R. glutinosa
      monoculture significantly decreased the relative abundances of Pseudomonadaceae
      and Burkholderiaceae, but significantly increased the relative abundances of
      Sphingomonadaceae and Streptomycetaceae. Moreover, the abundances of genera
      Pseudomonas, Azotobacter, Burkholderia, and Lysobacter, among others, were
      significantly lower in two-year monocultured soil than in one-year cultured soil.
      For potentially harmful/indicator microorganisms, the percentages of reads
      categorized to defense mechanisms (i.e., ATP-binding cassette (ABC) transporters,
      efflux transporter, antibiotic resistance) and biological metabolism (i.e., lipid
      transport and metabolism, secondary metabolites biosynthesis, transport and
      catabolism, nucleotide transport and metabolism, transcription) were
      significantly higher in two-year monocultured soil than in one-year cultured
      soil, but the opposite was true for potentially beneficial microorganisms, which
      might disrupt the equilibrium between beneficial and harmful microbes.
      Collectively, our results provide important insights into the shifts in genomic
      diversity and functional potentials of rhizosphere microbiome in response to R.
      glutinosa consecutive monoculture.

PMID- 30110930
TI  - Transcranial Direct Current Stimulation (tDCS) for Depression during Pregnancy:
      Scientific Evidence and What Is Being Said in the Media-A Systematic Review.
AB  - Major depression is the most frequent morbidity in pregnancy. The first-line
      therapies, psychopharmacologic treatment and psychotherapy, are either
      insufficient or may cause severe or teratogenic adverse events. As a result of
      its local limitation to the patient's brain, transcranial direct current
      stimulation (tDCS) could potentially be an ideal treatment for pregnant women
      with depression. A literature search was conducted in medical databases, globally
      published newspapers, search engines, and clinical trial registers to collect all
      articles on tDCS for the treatment of depression during pregnancy. The aim of
      this review was to investigate the scientific evidence of tDCS use for depression
      during pregnancy and to compare these results with the textual and emotional
      perception in the media as interventions during pregnancy are under particular
      surveillance. We detected 13 medical articles dealing with tDCS for depression in
      pregnancy. Overall, the scientific evidence as well as articles in the media for
      tDCS in pregnancy are sparse, but promising. Further studies are required in this
      specifically vulnerable population of pregnant women to generate evidence. It is
      likely that public interest will increase when the results of a pilot study in
      Canada are published.

PMID- 30110929
TI  - Mycobacteriophage Lysis Enzymes: Targeting the Mycobacterial Cell Envelope.
AB  - Mycobacteriophages are viruses that specifically infect mycobacteria, which
      ultimately culminate in host cell death. Dedicated enzymes targeting the complex
      mycobacterial cell envelope arrangement have been identified in mycobacteriophage
      genomes, thus being potential candidates as antibacterial agents. These comprise
      lipolytic enzymes that target the mycolic acid-containing outer membrane and
      peptidoglycan hydrolases responsive to the atypical mycobacterial peptidoglycan
      layer. In the recent years, a remarkable progress has been made, particularly on
      the comprehension of the mechanisms of bacteriophage lysis proteins activity and
      regulation. Notwithstanding, information about mycobacteriophages lysis
      strategies is limited and is mainly represented by the studies performed with
      mycobacteriophage Ms6. Since mycobacteriophages target a specific group of
      bacteria, which include Mycobacterium tuberculosis responsible for one of the
      leading causes of death worldwide, exploitation of the use of these lytic enzymes
      demands a special attention, as they may be an alternative to tackle multidrug
      resistant tuberculosis. This review focuses on the current knowledge of the
      function of lysis proteins encoded by mycobacteriophages and their potential
      applications, which may contribute to increasing the effectiveness of
      antimycobacterial therapy.

PMID- 30110931
TI  - Breakfast in Denmark. Prevalence of Consumption, Intake of Foods, Nutrients and
      Dietary Quality. A Study from the International Breakfast Research Initiative.
AB  - Breakfast is considered by many to be the most important meal of the day. This
      study examined the intake of nutrients and foods at breakfast among Danes and the
      relation to the overall dietary quality. Data were derived from the Danish
      National Survey on Diet and Physical Activity 2011-2013, a cross-sectional
      national food consumption study. A total of 3680 participants aged 6-75 years
      were included in the analyses of breakfast consumption. The Nutrient Rich Food
      Index 9.3 method was used to examine the overall dietary quality of the diet. The
      intake of nutrients and foods at breakfast were compared across dietary quality
      score tertiles by ANCOVA adjusted for energy and socio economic status. Breakfast
      was eaten frequently by children and adults and contributed with 18-20% of total
      energy intake. Breakfast was relatively high in dietary fibre, B vitamins,
      calcium and magnesium and low in added sugar, total fat, sodium, vitamin A and D.
      A decrease in the intake of added sugar, total fat and saturated fat and an
      increase in the intake of dietary fibre and most micronutrients were seen across
      tertiles of dietary quality scores. Commonly consumed foods provided at breakfast
      in Denmark included bread, breakfast cereals and dairy products as well as water,
      coffee and juice, while intakes of fruits, vegetables, cakes and soft drinks were
      low.

PMID- 30110932
TI  - Tracking Personal Health-Environment Interaction with Novel Mobile Sensing
      Devices.
AB  - The development of connected health devices has allowed for a more accurate
      assessment of a person's state under free-living conditions. In this work, we use
      two mobile sensing devices and investigate the correlation between individual's
      resting metabolic rate (RMR) and volatile organic compounds (VOCs) exposure
      levels. A total of 17 healthy, young, and sedentary office workers were
      recruited, measured for RMR with a mobile indirect calorimetry (IC) device, and
      compared with their corresponding predicted RMR values from the Academy of
      Nutrition and Dietetics' recommended epidemiological equation, the Mifflin-St
      Jeor equation (MSJE). Individual differences in the RMR values from the IC device
      and the epidemiological equation were found, and the subjects' RMRs were
      classified as normal, high, or low based on a cut-off of +/-200 kcal/day
      difference with respect to the predicted value. To study the cause of the
      difference, VOCs exposure levels of each participant's daytime working
      environment and nighttime resting environment were assessed using a second mobile
      sensing device for VOCs exposure detection. The results showed that all sedentary
      office workers had a low VOCs exposure level (<2 ppmC), and there was no obvious
      correlation between VOCs exposure and the RMR difference. However, an additional
      participant who was a worker in an auto repair shop, showed high VOCs exposure
      with respect to the sedentary office worker population and a significant
      difference between measured and predicted RMR, with a low RMR of 500 kcal/day
      difference. The mobile sensing devices have been demonstrated to be suitable for
      the assessment of direct information of human health-environment interactions at
      free-living conditions.

PMID- 30110935
TI  - Centimeter-Level Orbit Determination for TG02 Spacelab Using Onboard GNSS Data.
AB  - Tiangong-2, the second Chinese manned spacecraft, was launched into low Earth
      orbit on 15 September 2016. The dual-frequency geodetic GNSS receiver equipped on
      it is supporting a number of scientific experiments in orbit. This paper uses the
      onboard GNSS data from 3-31 December 2016 (in the attitude mode of three-axis
      Earth-pointing stabilization) to analyze the data quantity, as well as the code
      multipath error. Then, the dynamic and reduced-dynamic methods are adopted to
      perform the post Precise Orbit Determination (POD) based on the carrier phase
      measurements, respectively. After that, the orbit accuracy is evaluated using a
      number of tests, which include the analysis of observation residuals, Overlapping
      Orbit Differences (OODs), orbit comparison between dynamic and reduced-dynamic
      and Satellite Laser Ranging (SLR) validation. The results show that: (1) the
      average Root Mean Square (RMS) of the on-board GNSS phase fitting residuals is
      8.8 mm; (2) regarding the OODs determined by the reduced-dynamic method, the
      average RMS in radial (R), along-track (T) and cross-track (N) directions is 0.43
      cm, 1.34 cm and 0.39 cm, respectively, and there are no obvious system errors;
      (3) the orbit accuracy of TG02 determined by the reduced-dynamic method is
      comparable to that of the dynamic method, and the average RMS of their
      differences in R, T, N and 3D directions is 3.05 cm, 3.60 cm, 2.52 cm and 5.40
      cm, respectively; (4) SLR data are used to validate the reduced-dynamic orbits,
      and the average RMS along the station-satellite direction is 1.94 cm. It can be
      seen that both of these two methods can meet the demands of 3D centimeter-level
      orbit determination for TG02.

PMID- 30110933
TI  - Structure and Analysis of R1 and R2 Pyocin Receptor-Binding Fibers.
AB  - The R-type pyocins are high-molecular weight bacteriocins produced by some
      strains of Pseudomonas aeruginosa to specifically kill other strains of the same
      species. Structurally, the R-type pyocins are similar to "simple" contractile
      tails, such as those of phage P2 and Mu. The pyocin recognizes and binds to its
      target with the help of fibers that emanate from the baseplate structure at one
      end of the particle. Subsequently, the pyocin contracts its sheath and drives the
      rigid tube through the host cell envelope. This causes depolarization of the
      cytoplasmic membrane and cell death. The host cell surface-binding fiber is ~340
      A-long and is attached to the baseplate with its N-terminal domain. Here, we
      report the crystal structures of C-terminal fragments of the R1 and R2 pyocin
      fibers that comprise the distal, receptor-binding part of the protein. Both
      proteins are ~240 A-long homotrimers in which slender rod-like domains are
      interspersed with more globular domains-two tandem knob domains in the N-terminal
      part of the fragment and a lectin-like domain at its C-terminus. The putative
      substrate binding sites are separated by about 100 A, suggesting that binding of
      the fiber to the cell surface causes the fiber to adopt a certain orientation
      relative to the baseplate and this then triggers sheath contraction.

PMID- 30110934
TI  - CF3-Substituted Mollugin 2-(4-Morpholinyl)-ethyl ester as a Potential Anti
      inflammatory Agent with Improved Aqueous Solubility and Metabolic Stability.
AB  - Although mollugin, the main ingredient of the oriental medicinal herb Rubia
      cordifolia, has considerable anti-inflammatory effects, it has poor aqueous
      solubility as well as poor metabolic and plasma stability. To overcome these
      shortfalls, various mollugin derivatives have been synthesized and evaluated for
      their ability to inhibit U937 monocyte cell adhesion to HT-29 colonic epithelial
      cells in TNF-alpha- or IL-6-induced models of colon inflammation. The 2-(4
      morpholinyl)-ethyl ester of CF3-substituted mollugin (compound 15c) showed good
      water solubility, improved metabolic and plasma stability, and greater inhibitory
      activity than mesalazine in both the TNF-alpha- and IL-6-induced colonic
      epithelial cell adhesion assays, suggesting that 15c is a potential anti
      inflammatory agent.

PMID- 30110937
TI  - Genome-Wide Survey of Invertase Encoding Genes and Functional Characterization of
      an Extracellular Fungal Pathogen-Responsive Invertase in Glycine max.
AB  - Invertases are essential enzymes that irreversibly catalyze the cleavage of
      sucrose into glucose and fructose. Cell wall invertase (CWI) and vacuolar
      invertase (VI) are glycosylated proteins and exert fundamental roles in plant
      growth as well as in response to environmental cues. As yet, comprehensive
      insight into invertase encoding genes are lacking in Glycine max. In the present
      study, the systematic survey of gene structures, coding regions, regulatory
      elements, conserved motifs, and phylogenies resulted in the identification of
      thirty-two putative invertase genes in soybean genome. Concomitantly, impacts on
      gene expression, enzyme activities, proteins, and soluble sugar accumulation were
      explored in specific tissues upon stress perturbation. In combination with the
      observation of subcellular compartmentation of the fluorescent fusion protein
      that indeed exported to apoplast, heterologous expression, and purification in
      using Pichia pastoris system revealed that GmCWI4 was a typical extracellular
      invertase. We postulated that GmCWI4 may play regulatory roles and be involved in
      pathogenic fungi defense. The experimental evaluation of physiological
      significance via phenotypic analysis of mutants under stress exposure has been
      initiated. Moreover, our paper provides theoretical basis for elucidating
      molecular mechanisms of invertase in association with inhibitors underlying the
      stress regime, and will contribute to the improvement of plant performance to a
      diverse range of stressors.

PMID- 30110936
TI  - Biological Aspects of mTOR in Leukemia.
AB  - The mammalian target of rapamycin (mTOR) is a central processor of intra- and
      extracellular signals, regulating many fundamental cellular processes such as
      metabolism, growth, proliferation, and survival. Strong evidences have indicated
      that mTOR dysregulation is deeply implicated in leukemogenesis. This has led to
      growing interest in the development of modulators of its activity for leukemia
      treatment. This review intends to provide an outline of the principal biological
      and molecular functions of mTOR. We summarize the current understanding of how
      mTOR interacts with microRNAs, with components of cell metabolism, and with
      controllers of apoptotic machinery. Lastly, from a clinical/translational
      perspective, we recapitulate the therapeutic results in leukemia, obtained by
      using mTOR inhibitors as single agents and in combination with other compounds.

PMID- 30110938
TI  - A Window to Toxoplasma gondii Egress.
AB  - The Toxoplasma gondii cellular cycle has been widely studied in many lifecycle
      stages; however, the egress event still is poorly understood even though
      different types of molecules were shown to be involved. Assuming that there is no
      purpose or intentionality in biological phenomena, there is no such question as
      "Why does the parasite leaves the host cell", but "Under what conditions and
      how?". In this review we aimed to summarize current knowledge concerning T.
      gondii egress physiology (signalling pathways), structures, and route.

PMID- 30110940
TI  - Pervasive Modulation of Obesity Risk by the Environment and Genomic Background.
AB  - The prevalence of the so-called diseases of affluence, such as type 2 diabetes or
      hypertension, has increased dramatically in the last two generations. Although
      genome-wide association studies (GWAS) have discovered hundreds of genes involved
      in disease etiology, the sudden increase in disease incidence suggests a major
      role for environmental risk factors. Obesity constitutes a case example of a
      modern trait shaped by contemporary environment, although with considerable
      debates about the extent to which gene-by-environment (G*E) interactions
      accentuate obesity risk in individuals following obesogenic lifestyles. Although
      interaction effects have been robustly confirmed at the FTO locus, accumulating
      evidence at the genome-wide level implicates a role for polygenic risk-by
      environment interactions. Through a variety of analyses using the UK Biobank, we
      confirm that the genomic background plays a major role in shaping the
      expressivity of alleles that increase body mass index (BMI).

PMID- 30110941
TI  - Impact of Information Loss on Reconstruction Quality in Microwave Tomography for
      Medical Imaging.
AB  - This paper studies how limited information in data acquired by a wideband
      microwave tomography (MWT) system can affect the quality of reconstructed images.
      Limitations can arise from experimental errors, mismatch between the system and
      its model in the imaging algorithm, or losses in the immersion and coupling
      medium which are required to moderate this mismatch. We also present a strategy
      for improving reconstruction performance by discarding data that is dominated by
      experimental errors. The approach relies on recording transmitted signals in a
      wide frequency range, and then correlating the data in different frequencies. We
      apply this method to our wideband MWT prototype, which has been developed in our
      previous work. Using this system, we present results from simulated and
      experimental data which demonstrate the practical value of the frequency
      selection approach. We also propose a K-neighbour method to identify low quality
      data in a robust manner. The resulting enhancement in imaging quality suggests
      that this approach can be useful for various medical imaging scenarios, provided
      that data from multiple frequencies can be acquired and used in the
      reconstruction process.

PMID- 30110942
TI  - Astragaloside IV Attenuates Acetaminophen-Induced Liver Injuries in Mice by
      Activating the Nrf2 Signaling Pathway.
AB  - Acetaminophen (APAP) is a well-known antipyretic and analgesic drug. However, the
      accidental or intentional APAP overdose will induce liver injury and even acute
      liver failure. Astragaloside IV (AS-IV), a bioactive compound isolated from
      Astragali Radix, has been reported to have protective effects on the digestive
      and immune systems because of its anti-oxidant and anti-inflammatory properties.
      This study aims to observe whether AS-IV pretreatment provides protection against
      APAP-induced liver failure. The results of serum alanine/aspartate
      aminotransferases (ALT/AST) analysis, hepatic glutathione (GSH), and
      malondialdehyde (MDA) amounts, and liver superoxide dismutase (SOD) activity
      showed that AS-IV protected against APAP-induced hepatotoxicity. Liver
      histological observation further evidenced this protection provided by AS-IV. AS
      IV was found to reverse the APAP-induced increased amounts of pro-inflammatory
      cytokines, including interleukin 1beta (IL-1beta), interleukin 6 (IL-6) and tumor
      necrosis factor alpha (TNF-alpha). Western-blot analysis showed that AS-IV
      increased the transcriptional activation of nuclear factor erythroid 2-related
      factor 2 (Nrf2), and enhanced the expression of heme oxygenase 1 (HO-1) and
      reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H): quinone
      oxidoreductase 1 (NQO1) in the presence of APAP. AS-IV also decreased the
      expression of kelch-like ECH-associated protein-1 (Keap1). In conclusion, we
      demonstrated that AS-IV exerted a strong protection against APAP-induced
      hepatotoxicity by activating Nrf2 antioxidant signaling pathways.

PMID- 30110943
TI  - Tetragonia tetragonoides (Pall.) Kuntze (New Zealand Spinach) Prevents Obesity
      and Hyperuricemia in High-Fat Diet-Induced Obese Mice.
AB  - Tetragonia tetragonoides (Pall.) Kuntze, called New Zealand spinach (NZS), is an
      edible plant used in salad in Western countries and has been used to treat
      gastrointestinal diseases in traditional medicine. We examined the anti-obesity
      and anti-hyperuricemic effects of NZS and the underlying mechanisms in high-fat
      diet (HFD)-induced obese mice. Mice were fed a normal-fat diet (NFD); high-fat
      diet (HFD); HFD with 75, 150, or 300 mg/kg NZS extract; or 245 mg/kg Garcinia
      cambogia (GC) extract. NZS decreased body weight gain, total white adipose tissue
      (WAT), liver weight, and size of adipocytes and improved hepatic and plasma lipid
      profiles. With NZS, the plasma levels of the leptin and uric acid were
      significantly decreased while the levels of the adiponectin were increased.
      Furthermore, NZS decreased the expression levels of adipogenesis-related genes
      and xanthine oxidoreductase (XOR), which is involved in uric acid production,
      while increasing that of proteins associated with fatty acid oxidation. UPLC
      analysis revealed that NZS contained 6-methoxykaempferol-3-O-beta-d-glucosyl(1'''
      >2'')-beta-d-glucopyranoside, 6-methoxykaempferol-3-O-beta-d-glucosyl(1'''->2'')
      beta-d-glucopyranosyl-(6''''-caffeoyl)-7-O-beta-d-glucopyranoside, and 6,4'
      dimethoxykaempferol-3-O-beta-d-glucosyl(1'''->2'')-beta-d-glucopyranosyl-(6''''
      caffeoyl)-7-O-beta-d-glucopyranoside. These results suggest that NZS exerts anti
      obesity, anti-hyperlipidemia, and anti-hyperuricemic effects in HFD-induced obese
      mice, which are partly explained by regulation of lipid-metabolism-related genes
      and proteins and decreased expression of XOR.

PMID- 30110939
TI  - Overview of Trends in the Application of Metagenomic Techniques in the Analysis
      of Human Enteric Viral Diversity in Africa's Environmental Regimes.
AB  - There has been an increase in the quest for metagenomics as an approach for the
      identification and study of the diversity of human viruses found in aquatic
      systems, both for their role as waterborne pathogens and as water quality
      indicators. In the last few years, environmental viral metagenomics has grown
      significantly and has enabled the identification, diversity and entire genome
      sequencing of viruses in environmental and clinical samples extensively. Prior to
      the arrival of metagenomics, traditional molecular procedures such as the
      polymerase chain reaction (PCR) and sequencing, were mostly used to identify and
      classify enteric viral species in different environmental milieu. After the
      advent of metagenomics, more detailed reports have emerged about the important
      waterborne viruses identified in wastewater treatment plant effluents and surface
      water. This paper provides a review of methods that have been used for the
      concentration, detection and identification of viral species from different
      environmental matrices. The review also takes into consideration where
      metagenomics has been explored in different African countries, as well as the
      limitations and challenges facing the approach. Procedures including sample
      processing, experimental design, sequencing technology, and bioinformatics
      analysis are discussed. The review concludes by summarising the current thinking
      and practices in the field and lays bare key issues that those venturing into
      this field need to consider and address.

PMID- 30110944
TI  - Comparison of Bioelectrical Impedance Analysis, Slaughter Skinfold-Thickness
      Equations, and Dual-Energy X-ray Absorptiometry for Estimating Body Fat
      Percentage in Colombian Children and Adolescents with Excess of Adiposity.
AB  - Dual-energy X-ray absorptiometry (DXA) has been considered a reference method for
      measuring body fat percentage (BF%) in children and adolescents with an excess of
      adiposity. However, given that the DXA technique is impractical for routine field
      use, there is a need to investigate other methods that can accurately determine
      BF%. We studied the accuracy of bioelectrical impedance analysis (BIA)
      technology, including foot-to-foot and hand-to-foot impedance, and Slaughter
      skinfold-thickness equations in the measurement of BF%, compared with DXA, in a
      population of Latin American children and adolescents with an excess of
      adiposity. A total of 127 children and adolescents (11-17 years of age; 70%
      girls) from the HEPAFIT (Exercise Training and Hepatic Metabolism in
      Overweight/Obese Adolescent) study were included in the present work. BF% was
      measured on the same day using two BIA analysers (Seca(r) 206, Allers Hamburg,
      Germany and Model Tanita(r) BC-418(r), TANITA Corporation, Sportlife Tokyo,
      Japan), skinfold measurements (Slaughter equation), and DXA (Hologic Horizon DXA
      System(r), Quirugil, Bogota, Columbia). Agreement between measurements was
      analysed using t-tests, Bland-Altman plots, and Lin's concordance correlation
      coefficient (rhoc). There was a significant correlation between DXA and the other
      BF% measurement methods (r > 0.430). According to paired t-tests, in both sexes,
      BF% assessed by BIA analysers or Slaughter equations differ from BF% assessed by
      DXA (p < 0.001). The lower and upper limits of the differences compared with DXA
      were 6.3-22.9, 2.2-2.8, and -3.2-21.3 (95% CI) in boys and 2.3-14.8, 2.4-20.1,
      and 3.9-18.3 (95% CI) in girls for Seca(r) mBCA, Tanita(r) BC 420MA, and
      Slaughter equations, respectively. Concordance was poor between DXA and the other
      methods of measuring BF% (rhoc < 0.5). BIA analysers and Slaughter equations
      underestimated BF% measurements compared to DXA, so they are not interchangeable
      methods for assessing BF% in Latin American children and adolescents with excess
      of adiposity.

PMID- 30110945
TI  - Dietary Patterns and Cognitive Function among Older Community-Dwelling Adults.
AB  - Diet may be an important modifiable risk factor for maintenance of cognitive
      health in later life. This study aimed at examining associations between common
      dietary indices and dietary patterns defined by factor analysis and cognitive
      function in older community-dwelling adults. Dietary information for 1499
      participants from the Rancho Bernardo Study was collected in 1988-1992 and used
      to calculate the alternate Mediterranean diet score, Alternate Healthy Eating
      Index (AHEI)-2010 score and factor scores derived from factor analysis of
      nutrients. Global cognitive function, executive function, verbal fluency and
      episodic memory were assessed at approximate four-year intervals from 1988-2016.
      Linear mixed models were used to examine associations between dietary patterns
      and cognitive trajectories. Estimates for the highest vs. lowest tertile in
      models adjusting for age, sex, education, energy intake, lifestyle variables and
      retest effect showed greater adherence to the Mediterranean score was associated
      with better baseline global cognitive function (beta (95% CI) = 0.33 (0.11,
      0.55)). The AHEI-2010 score was not significantly associated with cognitive
      performance. Higher loading on a plant polyunsaturated fatty acid (PUFA)/vitamin
      E factor was associated with better baseline global cognitive function and
      executive function (beta = 0.22 (0.02, 0.42) and beta = -7.85 (-13.20, -2.47)). A
      sugar/low protein factor was associated with poorer baseline cognitive function
      across multiple domains. Dietary patterns were not associated with cognitive
      decline over time. Adherence to a healthy diet with foods high in PUFA and
      vitamin E and a low sugar to protein ratio, as typified by a Mediterranean diet,
      may be beneficial for cognitive health in late life.

PMID- 30110946
TI  - Synthesis and Biological Evaluation of New Cholinesterase Inhibitors for
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder mostly influencing the
      elderly, and causes death due to dementia. The main pathogenic feature connected
      with the progression of this multifactorial disease is the weakening of the
      cholinergic system in the brain. Cholinesterase (ChE) inhibitors are recognized
      as one of the choices in the treatment of AD. The inhibition of
      acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were approved as a
      therapeutic strategy to reduce the symptoms of AD and prevent its progression.
      The capacity of BChE is not completely known yet; rather, it is accepted to
      assume a part in a few disorders such as AD. Thus, BChE inhibitors may have a
      greater role for the treatment of AD in the future. In the present study, 2-(9
      acridinylamino)-2-oxoethyl piperazine/piperidine/morpholinecarbodithioate
      derivatives were synthesized in order to investigate anticholinesterase activity.
      Eight derivatives demonstrated a specific and promising action against BChE.
      Furthermore, compound 4n showed inhibitory activity against both enzymes. It was
      found that the active compounds were well tolerated in the cytotoxicity test.
      Possible interactions between the lead compound, 4n, and the BChE enzyme were
      determined through a docking study. The findings obtained within this paper will
      contribute to the development of new and effective synthetic anti-Alzheimer
      compounds, and will ideally encourage future screening against AD.

PMID- 30110947
TI  - A Review on Low-Grade Thermal Energy Harvesting: Materials, Methods and Devices.
AB  - Combined rejected and naturally available heat constitute an enormous energy
      resource that remains mostly untapped. Thermal energy harvesting can provide a
      cost-effective and reliable way to convert available heat into mechanical motion
      or electricity. This extensive review analyzes the literature covering broad
      topical areas under solid-state low temperature thermal energy harvesting. These
      topics include thermoelectricity, pyroelectricity, thermomagneticity, and
      thermoelasticity. For each topical area, a detailed discussion is provided
      comprising of basic physics, working principle, performance characteristics,
      state-of-the-art materials, and current generation devices. Technical
      advancements reported in the literature are utilized to analyze the performance,
      identify the challenges, and provide guidance for material and mechanism
      selection. The review provides a detailed analysis of advantages and
      disadvantages of each energy harvesting mechanism, which will provide guidance
      towards designing a hybrid thermal energy harvester that can overcome various
      limitations of the individual mechanism.

PMID- 30110950
TI  - Microbending Experiments on Pure Magnesium with Nonbasal Slip Orientation.
AB  - In the present study, in situ microbending experiments on magnesium single
      crystalline microcantilevers are presented. Microcantilevers with pentagonal
      cross-section were fabricated by focus ion beam. Two basic crystallographic
      orientations of the microcantilevers were investigated: {0001} and {10-10}, i.e.,
      the c-axis perpendicular to and parallel with the cantilever top surface,
      respectively. After bending, the longitudinal sections of the microcantilevers
      were analyzed using electron backscatter diffraction to investigate the crystal
      lattice rotations and accumulated deformations. The stress levels in the loaded
      cantilevers are strongly dependent on the crystal orientation. Extension twins
      were found in the {10-10} cantilevers.

PMID- 30110948
TI  - Sleeping Beauties: Horizontal Transmission via Resting Spores of Species in the
      Entomophthoromycotina.
AB  - Many of the almost 300 species of arthropod-pathogenic fungi in the
      Entomophthoromycotina (Zoopagomycota) are known for being quite host-specific and
      are able to cause epizootics. Most species produce two main types of spores,
      conidia and resting spores. Here, we present a review of the epizootiology of
      species of Entomophthoromycotina, focusing on their resting spores, and how this
      stage leads to horizontal transmission and persistence. Cadavers in which resting
      spores are produced can often be found in different locations than cadavers of
      the same host producing conidia. Resting spores generally are dormant directly
      after production and require specific conditions for germination. Fungal
      reproduction resulting from infections initiated by Entomophaga maimaiga resting
      spores can differ from reproduction resulting from conidial infections, although
      we do not know how commonly this occurs. Reservoirs of resting spores can
      germinate for variable lengths of time, including up to several months, providing
      primary infections to initiate secondary cycling based on conidial infections,
      and not all resting spores germinate every year. Molecular methods have been
      developed to improve environmental quantification of resting spores, which can
      exist at high titers after epizootics. Ecological studies of biological
      communities have demonstrated that this source of these spores providing primary
      inoculum in the environment can decrease not only because of germination, but
      also because of the activity of mycopathogens.

PMID- 30110949
TI  - Associations between Oxytocin Receptor Gene Polymorphisms, Empathy towards
      Animals and Implicit Associations towards Animals.
AB  - Oxytocin has been well researched in association with psychological variables and
      is widely accepted as a key modulator of human social behaviour. Previous work
      indicates involvement of oxytocin receptor gene (OXTR) single nucleotide
      polymorphisms (SNPs) in human-human empathy, however little is known about
      associations of OXTR SNPs with empathy and affective reactions of humans towards
      animals. Five OXTR SNPs previously found to associate with human social behaviour
      were genotyped in 161 students. Empathy towards animals and implicit associations
      were evaluated. A General Linear Model was used to investigate the OXTR alleles
      and allelic combinations along with socio-demographic variables and their
      influence on empathy towards animals. Empathy towards animals showed a
      significant association with OXTR SNP rs2254298; homozygous G individuals
      reported higher levels of empathy towards animals than heterozygous (GA). Our
      preliminary findings show, for the first time, that between allelic variation in
      OXTR and animal directed empathy in humans maybe associated, suggesting that
      OXTRs social behaviour role crosses species boundaries, warranting independent
      replication.

PMID- 30110951
TI  - Synthesis and Cytotoxicity Studies of Novel NHC*-Gold(I) Complexes Derived from
      Lepidiline A.
AB  - Ten novel N-heterocyclic carbene gold(I) complexes derived from lepidiline A (1,3
      dibenzyl-4,5-dimethylimidazolium chloride) are reported here with full
      characterisation and biological testing. (1,3-Dibenzyl-4,5-diphenylimidazol-2
      ylidene)gold(I) chloride (NHC*-AuCl) (1) was modified by substituting the
      chloride for the following: cyanide (2), dithiocarbamates (3-5), p
      mercaptobenzoate derivatives (12-14) and N-acetyl-l-cysteine derivatives (15-17).
      All complexes were synthesised in good yields of 57-78%. Complexes 2, 12, 13, and
      14 were further characterised by X-ray crystallography. Initial evaluation of the
      biological activity was conducted on all ten complexes against the multidrug
      resistant MCF-7topo breast cancer, HCT-116wt, and p53 knockout mutant HCT-116-/-
      colon carcinoma cell lines. Across the three cell lines tested, mainly single
      digit micromolar IC50 values were observed. Nanomolar activity was exhibited on
      the MCF-7topo cell line with 3 displaying an IC50 of 0.28 MUM +/- 0.03 MUM.
      Complexes incorporating a Au-S bond resulted in higher cytotoxic activity when
      compared to complexes 1 and 2. Theoretical calculations, carried out at the
      MN15/6-311++G(2df,p) computational level, show that NHC* is the more favourable
      ligand for Au(I)-Cl when compared to PPh3.

PMID- 30110952
TI  - Molecular Level Structure of Biodegradable Poly(Delta-Valerolactone) Obtained in
      the Presence of Boric Acid.
AB  - In this study, low molecular weight poly(delta-valerolactone) (PVL) was
      synthesized through bulk-ring openings polymerization of delta-valerolactone with
      boric acid (B(OH)3) as a catalyst and benzyl alcohol (BnOH) as an initiator. The
      resulting homopolymer was characterized with the aid of nuclear magnetic
      resonance (NMR) and mass spectrometry (MS) techniques to gain further
      understanding of its molecular structure. The electrospray ionization mass
      spectrometry (ESI-MS) spectra of poly(delta-valerolactone) showed the presence of
      two types of homopolyester chains-one terminated by benzyl ester and hydroxyl end
      groups and one with carboxyl and hydroxyl end groups. Additionally, a small
      amount of cyclic PVL oligomers was identified. To confirm the structure of PVL
      oligomers obtained, fragmentation of sodium adducts of individual polyester
      molecules terminated by various end groups was explored in ESI-MSn by using
      collision induced dissociation (CID) techniques. The ESI-MSn analyses were
      conducted both in positive- and negative ion mode. The comparison of the
      fragmentation spectra obtained with proposed respective theoretical fragmentation
      pathways allowed the structure of the obtained oligomers to be established at the
      molecular level. Additionally, using matrix-assisted laser desorption ionization
      time-of-flight mass spectrometry (MALDI-TOF-MS), it was proven that regardless of
      the degree of oligomerization, the resulting PVL samples were a mixture of two
      types of linear PVL oligomers differing in end groups and containing just a small
      amount of cyclic oligomers that tended to be not visible at higher molar masses.

PMID- 30110954
TI  - Many Kansas Worksites Offer Few Interventions to Reduce Occupational Sedentary
      Behavior.
AB  - The purpose of this study was to identify the extent to which sedentary behavior
      interventions are being implemented in Kansas worksites. The WorkWell KS Physical
      Activity Assessment was administered online to 111 worksites across Kansas from
      October 2016 through April 2018. Each worksite identified a point of contact to
      complete the worksite-level assessment. Four of the WorkWell KS Physical Activity
      Assessment's items assessed interventions that may reduce employees' sedentary
      behavior: offering point-of-decision prompts to reduce employees' sedentary
      behavior, offering a program for employees to reduce their sedentary time at
      work, having an organizational norm that allows employees to stand, stretch,
      and/or move during meetings at least every 30 minutes, and offering standing
      desks. All 111 worksites that participated in the WorkWell KS Physical Activity
      Workshop completed the WorkWell KS Physical Activity Assessment, resulting in a
      100% response rate. Most worksites (59%, n = 65) reported offering no
      information, program, policy, or environmental change interventions aimed to
      reduce sedentary behavior. The most commonly reported intervention offered by
      worksites to reduce employees' sedentary behavior was standing desks (32%, n =
      35). Overall, participating worksites reported implementing a few interventions
      that are designed to reduce sedentary behavior.

PMID- 30110953
TI  - Assessment of the Mutational Status of NSCLC Using Hypermetabolic Circulating
      Tumor Cells.
AB  - Molecular characterization is currently a key step in NSCLC therapy selection.
      Circulating tumor cells (CTC) are excellent candidates for downstream analysis,
      but technology is still lagging behind. In this work, we show that the mutational
      status of NSCLC can be assessed on hypermetabolic CTC, detected by their
      increased glucose uptake. We validated the method in 30 Stage IV NSCLC patients:
      peripheral blood samples were incubated with a fluorescent glucose analog (2
      NBDG) and analyzed by flow cytometry. Cells with the highest glucose uptake were
      sorted out. EGFR and KRAS mutations were detected by ddPCR. In sorted cells,
      mutated DNA was found in 85% of patients, finding an exact match with primary
      tumor in 70% of cases. Interestingly, in two patients multiple KRAS mutations
      were detected. Two patients displayed different mutations with respect to the
      primary tumor, and in two out of the four patients with a wild type primary
      tumor, new mutations were highlighted: EGFR p.746_750del and KRAS p.G12V.
      Hypermetabolic CTC can be enriched without the need of dedicated equipment and
      their mutational status can successfully be assessed by ddPCR. Finally, the
      finding of new mutations supports the possibility of probing tumor heterogeneity.

PMID- 30110955
TI  - A Forward Collision Warning System for Smartphones Using Image Processing and V2V
      Communication.
AB  - In this paper, we present a forward collision warning application for smartphones
      that uses license plate recognition and vehicular communication to generate
      warnings for notifying the drivers of the vehicle behind and the one ahead, of a
      probable collision when the vehicle behind does not maintain an established safe
      distance between itself and the vehicle ahead. The application was tested in both
      static and mobile scenarios, from which we confirmed the working of our
      application, even though its performance is affected by the hardware limitations
      of the smartphones.

PMID- 30110956
TI  - Effect of Different Anthocyanidin Glucosides on Lutein Uptake by Caco-2 Cells,
      and Their Combined Activities on Anti-Oxidation and Anti-Inflammation In Vitro
      and Ex Vivo.
AB  - The interactive effects on anti-oxidation and anti-inflammation of lutein
      combined with each of the six common anthocyanidin glucosides were studied in
      both chemical and cellular systems. The combined phytochemicals showed an
      antagonism in the inhibition of lipid oxidation in a liposomal membrane, but
      showed an additive effect on cellular antioxidant activity in Caco-2 cells.
      Lutein was an active lipoxygenase inhibitor at 2-12 MUM while anthocyanins were
      inactive. The concentration of lutein when it was used in combination with
      anthocyanins was 25-54% higher than when lutein was used alone (i.e., IC50 = 1.2
      MUM) to induce 50% of lipoxygenase inhibition. Only the combination of lutein
      with malvidin-3-glucoside showed anti-inflammatory synergy in the suppression of
      interleukin-8, and the synergy was seen at all three ratios tested. Some
      mixtures, however, showed anti-inflammatory antagonism. The presence of
      anthocyanins (5-7.5 MUM) did not affect lutein uptake (2.5-5 MUM) by Caco-2
      cells.

PMID- 30110958
TI  - One-Step Laser Encapsulation of Nano-Cracking Strain Sensors.
AB  - Development of flexible strain sensors that can be attached directly onto the
      skin, such as skin-mountable or wearable electronic devices, has recently
      attracted attention. However, such flexible sensors are generally exposed to
      various harsh environments, such as sweat, humidity, or dust, which cause noise
      and shorten the sensor lifetimes. This study reports the development of a nano
      crack-based flexible sensor with mechanically, thermally, and chemically stable
      electrical characteristics in external environments using a novel one-step laser
      encapsulation (OLE) method optimized for thin films. The OLE process allows
      simultaneous patterning, cutting, and encapsulating of a device using laser
      cutting and thermoplastic polymers. The processes are simplified for economical
      and rapid production (one sensor in 8 s). Unlike other encapsulation methods, OLE
      does not degrade the performance of the sensor because the sensing layers remain
      unaffected. Sensors protected with OLE exhibit mechanical, thermal, and chemical
      stability under water-, heat-, dust-, and detergent-exposed conditions. Finally,
      a waterproof, flexible strain sensor is developed to detect motions around the
      eye, where oil and sweat are generated. OLE-based sensors can be used in several
      applications that are exposed to a large amount of foreign matter, such as humid
      or sweaty environments.

PMID- 30110957
TI  - Comprehensive Analysis of Codon Usage on Rabies Virus and Other Lyssaviruses.
AB  - Rabies virus (RABV) and other lyssaviruses can cause rabies and rabies-like
      diseases, which are a persistent public health threat to humans and other
      mammals. Lyssaviruses exhibit distinct characteristics in terms of geographical
      distribution and host specificity, indicative of a long-standing diversification
      to adapt to the environment. However, the evolutionary diversity of lyssaviruses,
      in terms of codon usage, is still unclear. We found that RABV has the lowest
      codon usage bias among lyssaviruses strains, evidenced by its high mean effective
      number of codons (ENC) (53.84 +/- 0.35). Moreover, natural selection is the
      driving force in shaping the codon usage pattern of these strains. In summary,
      our study sheds light on the codon usage patterns of lyssaviruses, which can aid
      in the development of control strategies and experimental research.

PMID- 30110959
TI  - Effects of Polyphenol-Rich Foods on Human Health.
AB  - Recent evidence has suggested that polyphenol-rich foods intake may be associated
      with decreased risk of chronic diseases. The Special Issue "Effects of Polyphenol
      Rich Foods on Human Health" comprised 64 peer-reviewed papers on the most recent
      evidence regarding the dietary intake of polyphenols and polyphenol-rich foods,
      as well as their effect toward the prevention and treatment of non-communicable
      diseases. Original contributions and literature reviews demonstrated the
      potential protective effects of polyphenol-rich foods and their extracts toward
      cardiovascular diseases, certain cancers, and neurodegenerative diseases, mostly
      through anti-oxidant and chemo-preventive properties.

PMID- 30110960
TI  - Machine Learning in Agriculture: A Review.
AB  - Machine learning has emerged with big data technologies and high-performance
      computing to create new opportunities for data intensive science in the multi
      disciplinary agri-technologies domain. In this paper, we present a comprehensive
      review of research dedicated to applications of machine learning in agricultural
      production systems. The works analyzed were categorized in (a) crop management,
      including applications on yield prediction, disease detection, weed detection
      crop quality, and species recognition; (b) livestock management, including
      applications on animal welfare and livestock production; (c) water management;
      and (d) soil management. The filtering and classification of the presented
      articles demonstrate how agriculture will benefit from machine learning
      technologies. By applying machine learning to sensor data, farm management
      systems are evolving into real time artificial intelligence enabled programs that
      provide rich recommendations and insights for farmer decision support and action.

PMID- 30110962
TI  - Protomer-Dependent Electronic Spectroscopy and Photochemistry of the Model Flavin
      Chromophore Alloxazine.
AB  - Flavin chromophores play key roles in a wide range of photoactive proteins, but
      key questions exist in relation to their fundamental spectroscopic and
      photochemical properties. In this work, we report the first gas-phase
      spectroscopy study of protonated alloxazine (AL?H+), a model flavin chromophore.
      Laser photodissociation is employed across a wide range (2.34-5.64 eV) to obtain
      the electronic spectrum and characterize the photofragmentation pathways. By
      comparison to TDDFT quantum chemical calculations, the spectrum is assigned to
      two AL?H+ protomers; an N5 (dominant) and O4 (minor) form. The protomers have
      distinctly different spectral profiles in the region above 4.8 eV due to the
      presence of a strong electronic transition for the O4 protomer corresponding to
      an electron-density shift from the benzene to uracil moiety. AL?H+
      photoexcitation leads to fragmentation via loss of HCN and HNCO (along with small
      molecules such as CO2 and H2O), but the photofragmentation patterns differ
      dramatically from those observed upon collision excitation of the ground
      electronic state. This reveals that fragmentation is occurring during the excited
      state lifetime. Finally, our results show that the N5 protomer is associated
      primarily with HNCO loss while the O4 protomer is associated with HCN loss,
      indicating that the ring-opening dynamics are dependent on the location of
      protonation in the ground-state molecule.

PMID- 30110963
TI  - SpainUDP: The Spanish Undiagnosed Rare Diseases Program.
AB  - One of the IRDiRC goals for 2017-2027 is to achieve definitive diagnosis for rare
      undiagnosed diseases within one year, as delay in diagnosis remains one of the
      pending issues in the rare diseases field. The Spanish Undiagnosed Rare Diseases
      Program (SpainUDP) was created in response to this challenging scenario to cover
      patients' needs and after seeing the success of the Undiagnosed Diseases Program
      (UDP) in the USA. SpainUDP offers a multidisciplinary approach to those patients
      who have long sought a diagnosis without any success. During the first phase of
      the protocol, undiagnosed cases are sent to SpainUDP by individual patients or
      families, patient organizations or hospitals. After careful analysis of
      phenotype, data from sequencing experiments (WES) is processed with a standard
      pipeline and detailed standardized phenotypic information (mapped to the Human
      Phenotype Ontology, HPO) is connected to genetic data. In addition, the
      participation of SpainUDP in international initiatives such as the European
      projects RD-Connect and Solve RD, the Undiagnosed Diseases Network International
      (UDNI), and the MatchMaker Exchange (MME) platform, allows the establishment of a
      global data sharing strategy across multiple projects submitting data to these
      international initiatives. From the official beginning of the program (at the end
      of 2015) until early 2018, 147 cases were accepted in SpainUDP. During this time,
      37 cases (25%) dropped out the program due to several reasons. The remaining 110
      cases are distributed as follows: phenotypic and genotypic (WES) characterization
      was finished in 30 cases, of which 20 (67%) were diagnosed; 21 cases are pending
      on variants' validation by Sanger sequencing; in 25 cases, WES is ongoing and 34
      cases are being studied for deep phenotypic characterization. In conclusion,
      SpainUDP aims to achieve a diagnosis following two recommendations of the IRDiRC:
      the patients' diagnosis in as short a time as possible and the promotion of data
      sharing (especially genomic) at the international level.

PMID- 30110961
TI  - The Tiny Drosophila Melanogaster for the Biggest Answers in Huntington's Disease.
AB  - The average life expectancy for humans has increased over the last years.
      However, the quality of the later stages of life is low and is considered a
      public health issue of global importance. Late adulthood and the transition into
      the later stage of life occasionally leads to neurodegenerative diseases that
      selectively affect different types of neurons and brain regions, producing motor
      dysfunctions, cognitive impairment, and psychiatric disorders that are
      progressive, irreversible, without remission periods, and incurable. Huntington's
      disease (HD) is a common neurodegenerative disorder. In the 25 years since the
      mutation of the huntingtin (HTT) gene was identified as the molecule responsible
      for this neural disorder, a variety of animal models, including the fruit fly,
      have been used to study the disease. Here, we review recent research that used
      Drosophila as an experimental tool for improving knowledge about the molecular
      and cellular mechanisms underpinning HD.

PMID- 30110964
TI  - Hybrid Metal-Dielectric Nano-Aperture Antenna for Surface Enhanced Fluorescence.
AB  - A hybrid metal-dielectric nano-aperture antenna is proposed for surface-enhanced
      fluorescence applications. The nano-apertures that formed in the composite thin
      film consist of silicon and gold layers. These were numerically investigated in
      detail. The hybrid nano-aperture shows a more uniform field distribution within
      the apertures and a higher antenna quantum yield than pure gold nano-apertures.
      The spectral features of the hybrid nano-apertures are independent of the
      aperture size. This shows a high enhancement effect in the near-infrared region.
      The nano-apertures with a dielectric gap were then demonstrated theoretically for
      larger enhancement effects. The hybrid nano-aperture is fully adaptable to large
      scale availability and reproducible fabrication. The hybrid antenna will improve
      the effectiveness of surface-enhanced fluorescence for applications, including
      sensitive biosensing and fluorescence analysis.

PMID- 30110965
TI  - Photothermally Triggered Endosomal Escape and Its Influence on Transfection
      Efficiency of Gold-Functionalized JetPEI/pDNA Nanoparticles.
AB  - Plasmonic nanoparticles for drug delivery have attracted increasing interest over
      the last few years. Their localized surface plasmon resonance causes photothermal
      effects on laser irradiation, which allows for delivering drugs in a spatio
      temporally controlled manner. Here, we explore the use of gold nanoparticles
      (AuNP) as carriers for pDNA in combination with pulsed laser irradiation to
      induce endosomal escape, which is currently considered to be one of the major
      bottlenecks in macromolecular drug delivery on the intracellular level. In
      particular, we evaluate nanocomplexes composed of JetPEI (polyethylenimine)pDNA
      and 10 nm AuNP, which do not exhibit endosomal escape by themselves. After
      incubating HeLa cells with these complexes, we evaluated endosomal escape and
      transfection efficiency using low- and high-energy laser pulses. At low laser
      energy heat is produced by the nanocomplexes, while, at higher laser energy,
      explosive vapour nanobubbles (VNB) are formed. We investigated the ability of
      heat transfer and VNB formation to induce endosomal escape and we examine the
      integrity of pDNA cargo after inducing both photothermal effects. We conclude
      that JetPEI/pDNA/AuNP complexes are unable to induce meaningful transfection
      efficiencies because laser treatment causes either dysfunctionality of the cargo
      when VNB are formed or forms too small pores in the endosomal membrane to allow
      pDNA to escape in case of heating. We conclude that laser-induced VNB is the most
      suitable to induce effective pDNA endosomal escape, but a different nanocomplex
      structure will be required to keep the pDNA intact.

PMID- 30110967
TI  - Dielectric Properties and Switching Processes of Barium Titanate-Barium Zirconate
      Ferroelectric Superlattices.
AB  - This article is devoted to the investigation of the dielectric and repolarization
      properties of barium zirconate and barium titanate BaZrO3/BaTiO3 superlattices
      with a period of 13.322 nm on a monocrystal magnesium oxide (MgO) substrate.
      Synthesized superlattices demonstrated a ferroelectric phase transition at a
      temperature of approximately 393  degrees C, which is far higher than the Curie
      temperature of BaTiO3 thin films and bulk samples. The dielectric permittivity of
      the superlattice reached more than 104 at maximum. As the electric field
      frequency increased, the dielectric constant of the studied superlattice
      decreased over the entire study temperature range, but position of the maximum
      dielectric constant remained the same with changing frequency. The temperature
      dependence of the inverse dielectric permittivity 1/epsilon(T) for the studied
      samples shows that, in the investigated superlattice, both Curie-Weiss law and
      the law of "two" were followed. Additionally, the epsilon(T) dependences showed
      practically no temperature hysteresis with heating and cooling. Samples of
      synthesized superlattices had a relatively small internal bias field, which was
      directed from the superlattice towards the substrate.

PMID- 30110966
TI  - Application of fluorescence lifetime imaging microscopy of DNA binding dyes to
      assess radiation-induced chromatin compaction changes.
AB  - In recent years several approaches have been developed to address the chromatin
      status and its changes in eukaryotic cells under different conditions-but only
      few are applicable in living cells. Fluorescence lifetime imaging microscopy
      (FLIM) is a functional tool that can be used for the inspection of the molecular
      environment of fluorophores in living cells. Here, we present the use of single
      organic minor groove DNA binder dyes in FLIM for measuring chromatin changes
      following modulation of chromatin structure in living cells. Treatment with
      histone deacetylase inhibitors led to an increased fluorescence lifetime
      indicating global chromatin decompaction, whereas hyperosmolarity decreased the
      lifetime of the used dyes, thus reflecting the expected compaction. In addition,
      we demonstrate that time domain FLIM data based on single photon counting should
      be optimized using pile-up and counting loss correction, which affect the readout
      even at moderate average detector count rates in inhomogeneous samples. Using
      these corrections and utilizing Hoechst 34580 as chromatin compaction probe, we
      measured a pan nuclear increase in the lifetime following irradiation with X-rays
      in living NIH/3T3 cells thus providing a method to measure radiation-induced
      chromatin decompaction.

PMID- 30110968
TI  - A Review on Properties of Natural and Synthetic Based Electrospun Fibrous
      Materials for Bone Tissue Engineering.
AB  - Bone tissue engineering is an interdisciplinary field where the principles of
      engineering are applied on bone-related biochemical reactions. Scaffolds, cells,
      growth factors, and their interrelation in microenvironment are the major
      concerns in bone tissue engineering. Among many alternatives, electrospinning is
      a promising and versatile technique that is used to fabricate polymer fibrous
      scaffolds for bone tissue engineering applications. Copolymerization and polymer
      blending is a promising strategic way in purpose of getting synergistic and
      additive effect achieved from either polymer. In this review, we summarize the
      basic chemistry of bone, principle of electrospinning, and polymers that are used
      in bone tissue engineering. Particular attention will be given on biomechanical
      properties and biological activities of these electrospun fibers. This review
      will cover the fundamental basis of cell adhesion, differentiation, and
      proliferation of the electrospun fibers in bone tissue scaffolds. In the last
      section, we offer the current development and future perspectives on the use of
      electrospun mats in bone tissue engineering.

PMID- 30110969
TI  - Perylenequione Derivatives with Anticancer Activities Isolated from the Marine
      Sponge-Derived Fungus, Alternaria sp. SCSIO41014.
AB  - Seven new secondary metabolites classified as two perylenequinone derivatives (1
      and 2), an altenusin derivative (3), two phthalide racemates (4 and 5), and two
      phenol derivatives (6 and 7), along with twenty-one known compounds (8-28) were
      isolated from cultures of the sponge-derived fungus, Alternaria sp. SCSIO41014.
      The structures and absolute configurations of these new compounds (1-7) were
      determined by spectroscopic analysis, X-ray single crystal diffraction, chiral
      phase HPLC separation, and comparison of ECD spectra to calculations. Altertoxin
      VII (1) is the first example possessing a novel 4,8-dihydroxy-substituted
      perylenequinone derivative, while the phenolic hydroxy groups have commonly
      always substituted at C-4 and C-9. Compound 1 exhibited cytotoxic activities
      against human erythroleukemia (K562), human gastric carcinoma cells (SGC-7901),
      and hepatocellular carcinoma cells (BEL-7402) with IC50 values of 26.58 +/- 0.80,
      8.75 +/- 0.13, and 13.11 +/- 0.95 MUg/mL, respectively. Compound 11 showed
      selectively cytotoxic activity against K562, with an IC50 value of 19.67 +/- 0.19
      MUg/mL. Compound 25 displayed moderate inhibitory activity against Staphylococcus
      aureus with an MIC value of 31.25 MUg/mL.

PMID- 30110971
TI  - Toward Accurate Quantitative Elasticity Mapping of Rigid Nanomaterials by Atomic
      Force Microscopy: Effect of Acquisition Frequency, Loading Force, and Tip
      Geometry.
AB  - Atomic force microscopy (AFM) has emerged as a popular tool for the mechanical
      mapping of soft nanomaterials due to its high spatial and force resolution. Its
      applications in rigid nanomaterials, however, have been underexplored. In this
      work, we studied elasticity mapping of common rigid materials by AFM, with a
      focus on factors that affect the accuracy of elasticity measurements. We
      demonstrated the advantages in speed and noise level by using high frequency
      mechanical mapping compared to the classical force volume mapping. We studied
      loading force dependency, and observed a consistent pattern on all materials,
      where measured elasticity increased with loading force before stabilizing. Tip
      radius was found to have a major impact on the accuracy of measured elasticity.
      The blunt tip with 200 nm radius measured elasticity with deviation from nominal
      values up to 13% in different materials, in contrast to 122% by the sharp tip
      with 40 nm radius. Plastic deformation is believed to be the major reason for
      this difference. Sharp tips, however, still hold advantages in resolution and
      imaging capability for nanomaterials.

PMID- 30110972
TI  - Correction: Yoko, T., et al. Actinomycetes, an Inexhaustible Source of Naturally
      Occurring Antibiotics. Antibiotics 2018, 7, 45.
AB  - The authors wish to make the following corrections to this paper [...].

PMID- 30110970
TI  - Assessment of Genetic Diversity, Population Structure, and Evolutionary
      Relationship of Uncharacterized Genes in a Novel Germplasm Collection of Diploid
      and Allotetraploid Gossypium Accessions Using EST and Genomic SSR Markers.
AB  - This study evaluated the genetic diversity and population structures in a novel
      cotton germplasm collection comprising 132 diploids, including Glossypium
      klotzschianum and allotetraploid cotton accessions, including Glossypium
      barbadense, Glossypium darwinii, Glossypium tomentosum, Glossypium ekmanianum,
      and Glossypium stephensii, from Santa Cruz, Isabella, San Cristobal, Hawaiian,
      Dominican Republic, and Wake Atoll islands. A total of 111 expressed sequence tag
      (EST) and genomic simple sequence repeat (gSSR) markers produced 382 polymorphic
      loci with an average of 3.44 polymorphic alleles per SSR marker. Polymorphism
      information content values counted 0.08 to 0.82 with an average of 0.56. Analysis
      of a genetic distance matrix revealed values of 0.003 to 0.53 with an average of
      0.33 in the wild cotton collection. Phylogenetic analysis supported the subgroups
      identified by STRUCTURE and corresponds well with the results of principal
      coordinate analysis with a cumulative variation of 45.65%. A total of 123 unique
      alleles were observed among all accessions and 31 identified only in G.
      ekmanianum. Analysis of molecular variance revealed highly significant variation
      between the six groups identified by structure analysis with 49% of the total
      variation and 51% of the variation was due to diversity within the groups. The
      highest genetic differentiation among tetraploid populations was observed between
      accessions from the Hawaiian and Santa Cruz regions with a pairwise FST of 0.752
      (p < 0.001). DUF819 containing an uncharacterized gene named yjcL linked to
      genomic markers has been found to be highly related to tryptophan-aspartic acid
      (W-D) repeats in a superfamily of genes. The RNA sequence expression data of the
      yjcL-linked gene Gh_A09G2500 was found to be upregulated under drought and salt
      stress conditions. The existence of genetic diversity, characterization of genes
      and variation in novel germplasm collection will be a landmark addition to the
      genetic study of cotton germplasm.

PMID- 30110975
TI  - Effect of Electromagnetic Stirring on the Microstructure and Properties of Fe-Cr
      Co Steel.
AB  - High chromium steel has been synthesized by an induction furnace adopting
      electromagnetic stirring (EMS). Varying amounts of cobalt was added to obtain 3,
      6, and 12% Co in the steel. The melt was allowed to solidify with or without EMS
      in a rotary magnetic field. The effects of the varying cobalt content and the
      stirring have been characterized by the microstructural evolution and the
      consequent improvement in mechanical properties. The application of a rotary EMS
      during solidification has shown a significant effect on the grain refining, the
      reduction of element segregation, the promotion of eutectic volume fraction, and
      the consequent improvement of mechanical properties, including hardness and high
      temperature strength. The formation mechanism of the eutectic structure and the
      precipitation of M7C3 and M23C6 carbides was discussed according to the
      calculated phase diagram. The increment of cobalt content improved the eutectic
      volume fraction. Cobalt addition also enhanced the hardness and the yield tensile
      strength, provided that the ingot structure was homogenized by the EMS.

PMID- 30110973
TI  - Molecular and Biological Characterisation of Turnip mosaic virus Isolates
      Infecting Poppy (Papaversomniferum and P. rhoeas) in Slovakia.
AB  - In recent years, the accumulated molecular data of Turnip mosaic virus (TuMV)
      isolates from various hosts originating from different parts of the world
      considerably helped to understand the genetic complexity and evolutionary history
      of the virus. In this work, four complete TuMV genomes (HC9, PK1, MS04, MS15)
      were characterised from naturally infected cultivated and wild-growing Papaver
      spp., hosts from which only very scarce data were available previously.
      Phylogenetic analyses showed the affiliation of Slovak Papaver isolates to the
      world-B and basal-B groups. The PK1 isolate showed a novel intra-lineage
      recombination pattern, further confirming the important role of recombination in
      the shaping of TuMV genetic diversity. Biological assays indicated that the
      intensity of symptoms in experimentally inoculated oilseed poppy are correlated
      to TuMV accumulation level in leaves. This is the first report of TuMV in poppy
      plants in Slovakia.

PMID- 30110977
TI  - Relation between Motor and Cognitive Skills in Italian Basketball Players Aged
      between 7 and 10 Years Old.
AB  - There is evidence supporting a correlation between motor, attention and working
      memory in children. This present study focuses on children aged between 7 and 10
      years, who have been playing basketball in the last two years. The aim of this
      study is to verify the correlation between cognitive and motor abilities and to
      understand the importance of this correlation in basketball practice. A total of
      75 children who were 7.2-10.99 years old were assessed in terms of their
      attention, motor manual sequences and visuo-spatial working memory. A regression
      analysis was provided. In this sample, the motor abilities of children were found
      to be correlated with attention (denomination task, R2 = 0.07), visuo-spatial
      working memory (R2 = 0.06) and motor manual sequencing (aiming and catching task,
      R2 = 0.05; and manual dexterity task, R2 = 0.10). These correlations justify the
      suggestion to introduce deeper cognitive involvement during basketball training.
      The development of executive functions could have an important impact on
      basketball practice and the introduction of attention and memory tasks could help
      coaches to obtain optimal improvement in performance during the training
      sessions.

PMID- 30110976
TI  - Comparative Transcriptome Profiling of Two Tomato Genotypes in Response to
      Potassium-Deficiency Stress.
AB  - Tomato is a crop that requires a sufficient supply of potassium (K) for optimal
      productivity and quality. K+-deficiency stress decreases tomato yield and
      quality. To further delve into the mechanism of the response to K+-deficiency and
      to screen out low-K+ tolerant genes in tomatoes, BGISEQ-500-based RNA sequencing
      was performed using two tomato genotypes (low-K+ tolerant JZ34 and low-K+
      sensitive JZ18). We identified 1936 differentially expressed genes (DEGs) in JZ18
      and JZ34 at 12 and 24 h after K+-deficiency treatment. According to the Gene
      Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway
      analyses, the DEGs that changed significantly primarily included transcription
      factors, transporters, kinases, oxidative stress proteins, and hormone signaling
      and glycometabolism-related genes. The experimental results confirmed the induced
      expression of the responsive genes in the low-K+ signaling pathway. The largest
      group of DEGs comprised up to 110 oxidative stress-related genes. In total, 19
      ethylene response factors (ERFs) demonstrated differential expression between
      JZ18 and JZ34 in response to K+-deficiency. Furthermore, we confirmed 20 DEGs
      closely related to K+-deficiency stress by quantitative RT-PCR (qRT-PCR), some of
      which affected the root configuration, these DEGs could be further studied for
      use as molecular targets to explore novel approaches, and to acquire more
      effective K acquisition efficiencies for tomatoes. A hypothesis involving
      possible cross-talk between phytohormone signaling cues and reactive oxygen
      species (ROS) leading to root growth in JZ34 is proposed. The results provide a
      comprehensive foundation for the molecular mechanisms involved in the response of
      tomatoes to low K+ stress.

PMID- 30110974
TI  - Breast Cancer and Its Relationship with the Microbiota.
AB  - The microorganisms that live symbiotically in human beings are increasingly
      recognized as important players in health and disease. The largest collection of
      these microorganisms is found in the gastrointestinal tract. Microbial
      composition reflects both genetic and lifestyle variables of the host. This
      microbiota is in a dynamic balance with the host, exerting local and distant
      effects. Microbial perturbation (dysbiosis) could contribute to the risk of
      developing health problems. Various bacterial genes capable of producing estrogen
      metabolizing enzymes have been identified. Accordingly, gut microbiota is capable
      of modulating estrogen serum levels. Conversely, estrogen-like compounds may
      promote the proliferation of certain species of bacteria. Therefore, a crosstalk
      between microbiota and both endogenous hormones and estrogen-like compounds might
      synergize to provide protection from disease but also to increase the risk of
      developing hormone-related diseases. Recent research suggests that the microbiota
      of women with breast cancer differs from that of healthy women, indicating that
      certain bacteria may be associated with cancer development and with different
      responses to therapy. In this review, we discuss recent knowledge about the
      microbiome and breast cancer, identifying specific characteristics of the human
      microbiome that may serve to develop novel approaches for risk assessment,
      prevention and treatment for this disease.

PMID- 30110978
TI  - Suitability of Copper Nitride as a Wiring Ink Sintered by Low-Energy Intense
      Pulsed Light Irradiation.
AB  - Copper nitride particles have a low decomposition temperature, they absorb light,
      and are oxidation-resistant, making them potentially useful for the development
      of novel wiring inks for printing circuit boards by means of intense pulsed light
      (IPL) sintering at low-energy. Here, we compared the thermal decomposition and
      light absorption of copper materials, including copper nitride (Cu3N), copper(I)
      oxide (Cu2O), or copper(II) oxide (CuO). Among the copper compounds examined,
      copper nitride had the second highest light absorbency and lowest decomposition
      temperature; therefore, we concluded that copper nitride was the most suitable
      material for producing a wiring ink that is sintered by means of IPL irradiation.
      Wiring inks containing copper nitride were compared with those of wiring inks
      containing copper nitride, copper(I) oxide, or copper(II) oxide, and copper
      conversion rate and sheet resistance were also determined. Under low-energy
      irradiation (8.3 J cm-2), copper nitride was converted to copper at the highest
      rate among the copper materials, and provided a sheet resistance of 0.506 Omega
      sq-1, indicating that copper nitride is indeed a candidate material for
      development as a wiring ink for low-energy intense pulsed light sintering-based
      printed circuit board production processes.

PMID- 30110979
TI  - Soil Moisture Retrieval from the Chinese GF-3 Satellite and Optical Data over
      Agricultural Fields.
AB  - Timely and accurate soil moisture information is of great importance in
      agricultural monitoring. The Gaofen-3 (GF-3) satellite, the first C-band multi
      polarization synthetic-aperture radar (SAR) satellite in China, provides valuable
      data sources for soil moisture monitoring. In this study, a soil moisture
      retrieval algorithm was developed for the GF-3 satellite based on a
      backscattering coefficient simulation database. We adopted eight optical
      vegetation indices to determine the relationships between these indices and
      vegetation water content (VWC) by combining Landsat-8 data and field
      measurements. A backscattering coefficient database was built using an advanced
      integral equation model (AIEM). The effects of vegetation on backscattering
      coefficients were corrected using the water cloud model (WCM) to obtain the bare
      soil backscattering coefficient ( sigma s o i l  degrees  ). Then, soil moisture
      retrievals were obtained at HH, VV and HH+VV combination respectively by
      minimizing the observed bare soil backscattering coefficient ( sigma s o i l 
      degrees  ) and the AIEM-simulated backscattering coefficient ( sigma soil-simu 
      degrees  ). Finally, the proposed algorithm was validated in agriculture region
      of wheat and corn in China using ground soil moisture measurements. The results
      showed that the normalized difference infrared index (NDII) had the best fit with
      measured VWC values (R = 0.885) among the eight vegetation water indices; thus,
      it was adopted to correct the effects of vegetation. The proposed algorithm using
      GF-3 satellite data performed well in soil moisture retrieval, and the scheme
      combining HH and VV polarization exhibited the highest accuracy, with a root mean
      square error (RMSE) of 0.044 m3m-3, followed by HH polarization (RMSE = 0.049 m3m
      3) and VV polarization (RMSE = 0.053 m3m-3). Therefore, the proposed algorithm
      has good potential to operationally estimate soil moisture from the new GF-3
      satellite data.

PMID- 30110982
TI  - A Ceramic Diffusion Bonding Method for Passive LC High-Temperature Pressure
      Sensor.
AB  - Alumina ceramic is a highly promising material for fabricating high-temperature
      pressure sensors. In this paper, a direct bonding method for fabricating a
      sensitive cavity with alumina ceramic is presented. Alumina ceramic substrates
      were bonded together to form a sensitive cavity for high-temperature pressure
      environments. The device can sense pressure parameters at high temperatures. To
      verify the sensitivity performance of the fabrication method in high-temperature
      environments, an inductor and capacitor were integrated on the ceramic substrate
      with the fabricated sensitive cavity to form a wireless passive LC pressure
      sensor with thick-film integrated technology. Finally, the fabricated sensor was
      tested using a system test platform. The experimental results show that the
      sensor can realize pressure measurements above 900  degrees C, confirming that
      the fabricated sensitive cavity has excellent sealing properties. Therefore, the
      direct bonding method can potentially be used for developing all-ceramic high
      temperature pressure sensors for application in harsh environments.

PMID- 30110984
TI  - Model and Simulation Studies of the Method for Optimization of Dynamic Properties
      of Tachometric Anemometers.
AB  - Mechanical tachometric anemometers, based on the phenomenon of the exchange of
      momentum between the flow and rotating measuring element, represent an important
      class of instruments used in flow metrology. In particular, they are used in
      meteorological and ventilation measurements. Mechanical anemometers with rotating
      measuring element are, however, known for their drawback related to their poor
      dynamic properties resulting from relatively large dimensions and mechanical
      inertia of the measuring element. In these instruments, the phenomenon of
      overestimating the measured average velocity caused by the inertia of the rotor
      takes place. Optimization of the dynamics of the measurement process, as well as
      the estimation and minimization of the measurement uncertainty, can be performed
      based on mathematical model of anemometer. In this study, a new, original concept
      of optimization of dynamic properties of tachometric anemometers is proposed, and
      the results of model and simulation studies are presented. The new concept of
      measuring instrument is based on the use of feedback and active control of the
      rotor. The new method was tested using model research, where two types of flow
      velocity excitations were applied: sinusoidal and rectangular. The tests carried
      out showed that the developed method allows for minimization of the dynamic
      uncertainty of the measurement and minimizes the phenomenon of average flow
      velocity overestimation occurring in time-varying flows. It has been shown that
      the use of optimization system allows for approximately tenfold reduction of the
      error of average velocity measurement in the case of pulsating flows. In
      addition, the optimization systems allow for anemometer's transmission bandwidth
      to be extended about a hundred times. This creates new application possibilities
      for these instruments and allows for a large reduction of measurement
      uncertainty.

PMID- 30110983
TI  - Biological Degradation of Aflatoxin B1 by Cell-Free Extracts of Bacillus
      velezensis DY3108 with Broad PH Stability and Excellent Thermostability.
AB  - (1) Background: Aflatoxin contamination in food and grain poses serious problems
      both for economic development and public health protection, thus leading to a
      focus on an effective approach to control it; (2) Methods: Aflatoxin B1 (AFB1)
      degrading bacteria were isolated using a medium containing coumarin as the sole
      carbon source, and the biodegradation of AFB1 by the isolate was examined by high
      performance liquid chromatography, and liquid chromatography mass spectrometry;
      (3) Results: a bacterial strain exhibiting strong AFB1 degradation activity
      (91.5%) was isolated and identified as Bacillusvelezensis DY3108. The AFB1
      degrading activity was predominantly attributed to the cell-free supernatant of
      strain DY3108. Besides, it was heat-stable and resistant to proteinase K
      treatment but sensitive to sodium dodecyl sulfate treatment. The optimal
      temperature for the maximal degradation of AFB1 was 80  degrees C. Even more
      notable, the supernatant showed a high level of activity over a broad pH (4.0 to
      11.0) and exhibited the highest degradation (94.70%) at pH 8.0. Cytotoxicity
      assays indicated that the degradation products displayed significantly (p < 0.05)
      lower cytotoxic effects than the parent AFB1; (4) Conclusions: B.velezensis
      DY3108 might be a promising candidate for exploitation in AFB1 detoxification and
      bioremediation in food and feed matrices.

PMID- 30110981
TI  - Synthesis and Light-Induced Actuation of Photo-Labile 2-Pyridyl-1,2,3-Triazole
      Ru(bis-bipyridyl) Appended Ferrocene Rotors.
AB  - To realise useful control over molecular motion in the future an extensive
      toolbox of both actionable molecules and stimuli-responsive units must be
      developed. Previously, our laboratory has reported 1,1'-disubstituted ferrocene
      (Fc) rotor units which assume a contracted/pi-stacked conformation until
      complexation of cationic metal ions causes rotation about the Ferrocene (Fc)
      molecular 'ball-bearing'. Herein, we explore the potential of using the
      photochemical ejection of [Ru(2,2'-bipyridyl)2]2+ units as a stimulus for the
      rotational contraction of new ferrocene rotor units. Fc rotors with both
      'regular' and 'inverse' 2-pyridyl-1,2,3-triazole binding pockets and their
      corresponding [Ru(2,2'-bipyridyl)2]2+ complexes were synthesised. The rotors and
      complexes were characterised using nuclear magnetic resonance (NMR) and
      ultraviolet (UV)-visible spectroscopies, Electro-Spray Ionisation Mass
      Spectrometry (ESI-MS), and electrochemistry. The 1,1'-disubstituted Fc ligands
      were shown to pi-stack both in solution and solid state. Density Functional
      Theory (DFT) calculations (CAM-B3LYP/6-31G(d)) support the notion that
      complexation to [Ru(2,2'-bipyridyl)2]2+ caused a rotation from the syn- to the
      anti-conformation. Upon photo-irradiation with UV light (254 nm), photo-ejection
      of the [Ru(2,2'-bipyridyl)2(CH3CN)2]2+ units in acetonitrile was observed. The re
      complexation of the [Ru(2,2'-bipyridyl)2]2+ units could be achieved using acetone
      as the reaction solvent. However, the process was exceedingly slowly.
      Additionally, the Fc ligands slowly decomposed when exposed to UV irradiation
      meaning that only one extension and contraction cycle could be completed.

PMID- 30110980
TI  - Protein Import into the Endosymbiotic Organelles of Apicomplexan Parasites.
AB  - : The organelles of endosymbiotic origin, plastids, and mitochondria, evolved
      through the serial acquisition of endosymbionts by a host cell. These events were
      accompanied by gene transfer from the symbionts to the host, resulting in most of
      the organellar proteins being encoded in the cell nuclear genome and trafficked
      into the organelle via a series of translocation complexes. Much of what is known
      about organelle protein translocation mechanisms is based on studies performed in
      common model organisms; e.g., yeast and humans or Arabidopsis. However, studies
      performed in divergent organisms are gradually accumulating. These studies
      provide insights into universally conserved traits, while discovering traits that
      are specific to organisms or clades. Apicomplexan parasites feature two
      organelles of endosymbiotic origin: a secondary plastid named the apicoplast and
      a mitochondrion. In the context of the diseases caused by apicomplexan parasites,
      the essential roles and divergent features of both organelles make them prime
      targets for drug discovery. This potential and the amenability of the
      apicomplexan Toxoplasma gondii to genetic manipulation motivated research about
      the mechanisms controlling both organelles' biogenesis. Here we provide an
      overview of what is known about apicomplexan organelle protein import. We focus
      on work done mainly in T. gondii and provide a comparison to model organisms.

PMID- 30110985
TI  - Seed-Specific Gene MOTHER of FT and TFL1(MFT) Involved in Embryogenesis, Hormones
      and Stress Responses in Dimocarpus longan Lour.
AB  - Mother of FT and TFL1 (MFT) belongs to phosphatidylethanolamine-binding protein
      (PEBP) family, which plays an important role in flowering time regulation, seed
      development, and germination. To gain insight into the molecular function of
      DlMFT in Dimocarpus longan Lour., we isolated DlMFT and its promoter sequence
      from longan embryogenic callus (EC). Bioinformatic analysis indicated that the
      promoter contained multiphytohormones and light responsive regulatory elements.
      Subcellular localization showed that the given the DlMFT signal localized in the
      nucleus, expression profiling implied that DlMFT showed significant upregulation
      during somatic embryogenesis (SE) and zygotic embryogenesis (ZE), and particular
      highly expressed in late or maturation stages. The accumulation of DlMFT was
      mainly detected in mature fruit and seed, while it was undetected in abortive
      seeds, and notably decreased during seed germination. DlMFT responded
      differentially to exogenous hormones in longan EC. Auxins, salicylic acid (SA)
      and methyl jasmonate (MeJa) suppressed its expression, however, abscisic acid
      (ABA), brassinosteroids (BR) showed the opposite function. Meanwhile, DlMFT
      differentially responded to various abiotic stresses. Our study revealed that
      DlMFT might be a key regulator of longan somatic and zygotic embryo development,
      and in seed germination, it is involved in complex plant hormones and abiotic
      stress signaling pathways.

PMID- 30110986
TI  - Development of MoSe2 Nano-Urchins as a Sensing Platform for a Selective Bio
      Capturing of Escherichia. coli Shiga Toxin DNA.
AB  - The present study was aimed to develop "fluorine doped" tin oxide glass electrode
      with a MoSe2 nano-urchin based electrochemical biosensor for detection of
      Escherichia. coli Shiga toxin DNA. The study comprises two conductive electrodes,
      and the working electrodes were drop deposited using MoSe2 nano-urchin, and DNA
      sequences specific to Shiga toxin Escherichia. coli. Morphological
      characterizations were performed using Fourier transforms infrared
      spectrophotometer; X-ray diffraction technique and scanning electron microscopy.
      All measurements were done using methylene blue as an electrochemical indicator.
      The proposed electrochemical geno-sensor showed good linear detection range of 1
      fM-100 MUM with a low detection limit of 1 fM where the current response
      increased linearly with Escherichia. coli Shiga toxin dsDNA concentration with R2
      = 0.99. Additionally, the real sample was spiked with the dsDNA that shows
      insignificant interference. The results revealed that the developed sensing
      platform significantly improved the sensitivity and can provide a promising
      platform for effective detection of biomolecules using minute samples due to its
      stability and sensitivity.

PMID- 30110987
TI  - Characteristics of Gorilla-Specific Lactobacillus Isolated from Captive and Wild
      Gorillas.
AB  - Lactic acid bacteria (LAB) reside in a wide range of mammals, such as
      autochthonous intestinal bacteria. In this paper, we present the phenotypic and
      phylogenetic characteristics of gorilla-specific LAB. Lactobacillus gorillae
      previously isolated from the wild and captive western lowland gorillas (Gorilla
      gorilla gorilla)-were successfully isolated from wild mountain gorillas (Gorilla
      gorilla beringei) in addition to other captive and wild western lowland gorillas.
      The strains from wild gorillas could ferment D-xylose, arbutine, cellobiose, and
      trehalose better than those from captive gorillas. By contrast, tolerance to NaCl
      was higher in isolates from captive gorillas than in those from wild gorillas.
      This tendency may have been induced by regular foods in zoos, which contain
      sufficient amount of salts but less amount of indigestible fiber and plant
      secondary metabolites compared to foods in the wild. All strains of L. gorillae
      showed inhibitory activities to enteric pathogenic bacteria; however, the
      activity was significantly higher for strains from wild gorillas than for those
      from captive gorillas. This may have been induced by the captive condition with
      routine veterinary intervention. Since L. gorillae can grow in the
      gastrointestinal tract of gorillas in captivity, the strains from wild mountain
      gorillas are potential probiotics for gorillas under captive conditions.

PMID- 30110988
TI  - Validation of Serbian Version of Dysfunctional Voiding Symptom Score (DVSS)
      Questionnaire.
AB  - OBJECTIVE: The aims of our study were to translate the dysfunctional voiding
      symptom score (DVSS) from English to Serbian; culturally adopt the items; assess
      the internal consistency and the test-retest reliability of DVSSSR in patients
      with dysfunctional voiding (DV); evaluate and test the construct and divergent
      validity of DVSSSR against demographic parameters (gender and education); and
      examine the level of explained variability for each item of DVSSSR against
      demographic parameters (gender and education). METHODS: The cross-sectional
      observational study included 50 patients with dysfunctional voiding aged 5 years
      and above. The DVSS questionnaire was translated from English into Serbian by the
      forward-backward method. Internal consistency was assessed with Cronbach alpha
      and test-retest reliability with intraclass correlation coefficient (ICC). For
      validity testing we performed construct and divergent validity analyses. RESULTS:
      There was excellent internal consistency for every item except for Item 6 (0.787)
      and Item 3 (0.864), where internal consistency was good. The observed test/retest
      ICC for average measures was more than 0.75 (excellent) for all DVSSSR items.
      Gender and educational level does not correlate significantly with each item of
      DVSSSR (p > 0.05). For divergent validity, there were no significant differences
      in mean values of each item of DVSSSR between genders and different levels of
      education (p > 0.05). Variability that can be explained for gender and
      educational level was below 10%. CONCLUSION: Translated DVSSSR is of adequate
      validity and reliability for assessing DV in children.

PMID- 30110990
TI  - A modified paranotal theory of insect wing origin.
AB  - The theory of Kukalova-Peck ('78) is examined and rejected except for the
      hypothesis of the partially pleural origin of wings. Data suggest that the
      arthropods ancestral to insects left the water, and that movable precursors of
      the wings, possibly exopodites, were immobilized and fused with the tergum to
      form part of the complex paranota. Later, during insect adaptation for flight,
      parts of the complex paranota were separated secondarily and became wings.

PMID- 30110991
TI  - A crustacean statocyst with only three hairs: Light and scanning electron
      microscopy.
AB  - Standard histological and SEM techniques have been used to examine the pair of
      statocyst organs located in the telson of the isopod, Cyathara polita. Each organ
      is formed as an invagination of the dorsal cuticle of the telson. The
      invagination narrows to form a stalk between the statocyst and dorsal surface. A
      canal courses longitudinally through this stalk and forms a continuous channel
      between the lumen of the cyst and the external environment. On the luminal floor
      of each statocyst, there are three pits; each correlates with a nodule protruding
      from the ventro-medial wall. From each pit, a single, bifurcating hair projects
      dorsally to contact the single concretion within the statocyst lumen. No other
      static organs have been found in this animal. Thus, maintenance of equilibrium in
      this species appears to be under the control of but six hairs, three in each
      statocyst. Innervation of each statocyst is provided by a branch of a nerve which
      connects anteriorly with the last abdominal ganglion.

PMID- 30110992
TI  - A quantitative analysis of mitotic gradients during early development in
      Calliphora erythrocephala Meig. (Diptera).
AB  - Mitotic waves during superficial cleavage and early gastrulation were analyzed
      quantitatively in Calliphora. Three consecutive patterns are present: (1) a
      monotonic anterioposterior mitotic gradient during early superficial cleavage;
      (2) a double mitotic gradient from the anterior and posterior poles during
      superficial cleavage, especially toward the end of the period; and (3) more
      complicated patterns with intermediate mitotic centers during the last
      superficial cleavage division and during early gastrulation. Mitotic gradients
      are absent in many eggs during early superficial cleavage, but they then become
      ubiquitous. The gradients are longitudinal; no transverse component was detected
      before gastrulation. Anterior and posterior gradient patterns are not mirror
      images of each other; mitotic activity always starts earlier anteriorly. The
      gradients are accompanied by a pronounced increase in interphase length. The
      mitotic gradients are compared with the morphogenetic gradients predicted in a
      current model for pattern specification in insect eggs.

PMID- 30110989
TI  - Intakes, Adequacy, and Biomarker Status of Iron, Folate, and Vitamin B12 in Maori
      and Non-Maori Octogenarians: Life and Living in Advanced Age: A Cohort Study in
      New Zealand (LiLACS NZ).
AB  - Advanced-age adults may be at risk of iron, folate, and vitamin B12 deficiency
      due to low food intake and poor absorption. This study aimed to investigate the
      intake and adequacy of iron, folate, and vitamin B12 and their relationship with
      respective biomarker status. Face-to-face interviews with 216 Maori and 362 non
      Maori included a detailed dietary assessment using 2 * 24-h multiple pass
      recalls. Serum ferritin, serum iron, total iron binding capacity, transferrin
      saturation, red blood cell folate, serum folate, serum vitamin B12 and hemoglobin
      were available at baseline. Regression techniques were used to estimate the
      association between dietary intake and biomarkers. The Estimated Average
      Requirement (EAR) was met by most participants (>88%) for dietary iron and
      vitamin B12 (>74%) but less than half (>42%) for folate. Increased dietary folate
      intake was associated with increased red blood cell (RBC) folate for Maori (p =
      0.001), non-Maori (p = 0.014) and serum folate for Maori (p < 0.001). Folate
      intake >215 ug/day was associated with reduced risk of deficiency in RBC folate
      for Maori (p = 0.001). Strategies are needed to optimize the intake and
      bioavailability of foods rich in folate. There were no significant associations
      between dietary iron and vitamin B12 intake and their respective biomarkers,
      serum iron and serum vitamin B12.

PMID- 30110993
TI  - A scanning electron microscopic study of the molar surfaces of the mandibles of
      the brine shrimp (Cl. Branchiopoda: O. Anostraca).
AB  - Scanning electron microscopy was used to characterize the external morphology of
      the molar surface of the mandibles of the brine shrimp, Artemia salina. Unlike
      many other branchiopod crustaceans, Artemia has symmetrical mandibles, ie, the
      molar surfaces of the two mandibles of an individual are similar in size and
      surface structure. Each molar area has three basic regions: the anterio-ventral
      region, posterio-dorsal region, and transition zone. On the anterio-ventral
      region there are complex, parallel furrows and ridges, which are specializations
      for clasping masses of fine, particulate food. The general surface of this ridged
      area is flat, except at the ventral and anterior edges, where there is a fringe
      of long projections that probably serve to retain food in the space between the
      paired mandibles. The posterio-dorsal region, which has simpler, more sparse
      cuticular projections, is adapted for reception of food. Stereomicrographs reveal
      that the general surface of this region is sloped and thus forms a cleft along
      the posterio-dorsal margin of the two apposed molar surfaces. Anatomical
      relstionships suggest that the cleft is an adaptation for accommodating
      maxillular setae that push food forward onto the mandibles. The transition zone
      has cuticular specializations that are morphologically intermediate between those
      of the anterio-ventral and posterio-dorsal regions. Three types of pores,
      possibly openings of glands or sensilla, were observed in the cuticle of the
      molar surface.

PMID- 30110994
TI  - Ultrastrucuture of the fat body of the reproductive pair in higher termites.
AB  - The fine structure of the fat body of the higher termite king and queen has been
      studied both in species with (Macrotermes bellicosus, M. subhyalinus) and without
      (Cubitermes fungifaber) tracheal rosettes. There is a very pronounced sexual
      dimorphism. The adipocytes of the queen are highly specialized for protein
      synthesis and secretion; they store only a small quantity of reserves. The
      adipocytes of the king are not specialized in protein synthesis, but accumulate
      large amounts of reserve substances. The previously proposed different functions
      of the termite queen's fat body are discussed; it appears to be mainly concerned
      with vitellogenesis.

PMID- 30110995
TI  - Ultrastructural studies of the epidermal leydig cell in larvae of Salamandra
      salamandra (caudata, salamandrida).
AB  - Epidermal Leydig cells observed in the ventral epidermis of Salamandra salamandra
      larvae from birth until metamorphosis are characterized by large vesicles and a
      supporting Langerhans net. They decline in number after birth and disappear
      entirely after metamorphosis. The cells change in structure and become larger,
      thus indicating a process of degeneration. The Leydig cells are continuously
      removed by macrophagelike cells after birth.

PMID- 30110996
TI  - Ultrastructural aspects of mechano- and chemoreceptors in Branchiobdella
      pentodonta (annelida, oligochaeta).
AB  - The surface receptors in Branchiobdella pentodonta consist of "sense buttons"
      prevalent on the prostomium, isolated sense cells all along the body of the
      animal, and free nerve endings. The "sense buttons" are uni- and multiciliated
      neurosensitive elements and supporting cells together with mucus glandular
      processes and muscle fibers. In the neurosensitive elements the cilia are always
      surrounded by cytoplasmic extroversion. The cytoplasm of the apical zone has
      abundant small dense granules, mitochondria, bands of tonofilaments, and
      microtubules. The cilium of uniciliated elements originates from three short
      roots. The highly vacuolated support cells surround the neurosensitive elements,
      separating them from each other. The "sense buttons" appear to be
      mechanoreceptors and chemoreceptors, and the isolated sense cells tactile
      mechanoreceptors, as are the free nerve endings. The surface receptors are
      compared with those of other Oligochaeta and Hirudinea.

PMID- 30110997
TI  - Ultrastructural study of midgut embryonic cytodifferentiation in the phasmid
      Clitumnus extradentatus Br.
AB  - The embryonic cytodifferentiation of Clitumnus midgut occurs very late when
      compared to that of other tissues in the embryo. It proceeds from hemolymph
      towards the yolk, first at the level of the muscular-connective tissue sheath, by
      the appearance of myofilaments in external-then internal-muscle fibers. In the
      gut epithelium, cytodifferentiation begins with the appearance of infoldings of
      the basal membranes of the cells. Then, microvilli and continuous junctions form
      at the apices of the cells. Microvilli appear in crypts, which seem to represent
      localized dilatations of intercellular spaces. At the level of these crypts,
      continuous junctions are formed somewhat later than are microvilli. This midgut
      differentiation coincides with deposition of the third embryonic (first larval)
      cuticle, and with a high titer of ecdysteroids.

PMID- 30110998
TI  - Two sperm types in the spermatozeugmata of Tubifex tubifex (annelida,
      oligochaeta).
AB  - The spermatozeugmata (sperm bundles lacking a distinct wall) from the
      spermathecae of Tubifex tubifex are composed of two different zones: an internal
      axial cylinder containing conventional spermatozoa and an external cortex
      composed of modified spermatozoa, tightly packed together. The conventional
      spermatozoa conform to the classical clitellate scheme: very long and thin with a
      complex acrosome, a filiform nucleus, small mitochondria, and a flagellum with Y
      links and beta glycogen granules as accessory structures. The modified
      spermatozoa show "empty" acrosomes, degenerating nuclei, and tails which contain
      gamma glycogen granules. The tails are helically wound around the spermatozeugma
      and are connected to each other by junctional complexes. The tips of the cortical
      tails are free and move with a metachronal wave. The presence of two sperm types
      in tubificids is discussed and a protective function for the modified cortical
      spermatozoa is proposed.

PMID- 30110999
TI  - Ultrastructure of the ovary and oogenesis in the polychaete Capitella jonesi
      (Hartman, 1959).
AB  - Ultrastructural features of the ovary and oogenesis in the polychaete Capitella
      jonesi (Hartman, '59) have been described. The ovaries are paired, sac-like
      follicles suspended by mesenteries in the ventral coelom throughout the midbody
      region of the mature worm. Oogenesis is unsynchronized and occurs entirely within
      the ovary, where developing gametogenic stages are segregated spatially within a
      germinal and a growth zone. Multiplication of oogonia and differentiation of
      oocytes into the late stages of vitellogenesis occur in the germinal region of
      the ovary, whereas late-stage vitellogenic oocytes and mature eggs are located in
      a growth zone. Follicle cells envelop the oocytes in the germinal zone of the
      ovary and undergo hypertrophy and ultrastructural changes that correlate with the
      onset of vitellogenesis. These changes include the development of extensive
      arrays of rough ER and numerous Golgi complexes, formation of microvilli along
      the surface of the ovary, and the initiation of extensive endocytotic activity.
      Oocytes undergo similar, concomitant changes such as the differentiation of
      surface microvilli, the formation of abundant endocytotic pits and vesicles along
      the oolemma, and the appearance of numerous Golgi complexes, cisternae of rough
      ER, and yolk bodies. Yolk synthesis appears to occur by both autosynthetic and
      heterosynthetic processes involving the conjoined efforts of the Golgi complex
      and rough ER of the oocyte and the probable addition of extraovarian
      (heterosynthetic) yolk precursors. Evidence is presented that implicates the
      follicle cells in the synthesis of yolk precursors for transport to the oocytes.
      At ovulation, mature oocytes are released from the overy after the overlying
      follicle cells apparently withdraw. Bundles of microfilaments within the follicle
      cells may play a role in this withdrawal process.

PMID- 30111000
TI  - An investigation of the prolactin-thyroxine synergism in newt limb regeneration.
AB  - The use of hormone replacement to support limb regeneration in hypophysectomized
      newts has been the subject of many investigations. Growth hormone, as well as
      prolactin (PL) in combination with exogenously supplied thyroxine, have all been
      shown to he effective. However, the bovine growth hormone used to support limb
      regeneration was contaminated by prolactin and thyroidstimulating hormone (TSH).
      The present investigation evaluates the significance of (1) prolactin
      contamination and (2) endogenous thyroxine synthesis resulting from TSH
      contamination on limb regeneration in hypophysectomized newts. The effect of
      supplying exogenous thyroxine was also evaluated. Our studies showed that when
      hypophysectomized newts were injected with contamination levels of PL and TSH,
      regeneration occurred, suggesting that the newt's thyroid synthesized sufficient
      thyroxine to support a prolactin-thyroxine synergism. The endogenous thyroxine
      was synthesized by thyroid glands that were indistinguishable from those of
      saline-injected, hypophysectomized controls.

PMID- 30111001
TI  - A stereological analysis of developing egg chambers in Ephestia kuhniella.
AB  - A polytrophic ovariole of the flour moth, Ephestia kuhniella, is composed of a
      linear series of increasingly mature egg chambers, each consisting of an oocyte,
      an interconnected cluster of seven nurse cells, and a covering layer of follicle
      cells. This study describes changes in the volume of each component as a function
      of the position of the egg chamber in the ovariole. Analysis of the growth curve
      of the Ephestia oocyte yields two possible correlations between accelerated
      oocyte growth and ultrastructural events enhancing the supply of yolk materials
      to the oocyte: the first is the initiation of yolk synthesis by the follicle cell
      layer and its transfer to the oocyte, and the second is the formation of channels
      between the follicle cells allowing hemolymph to gain access to the oocyte. An
      Ephestia oocyte increases in volume from approximately 2.5 * 103 MUm3 to
      approximately 2.0 * 107 MUm3 over an average series of 58 egg chambers.

PMID- 30111002
TI  - A three dimensional serial reconstruction of neuronal distributions in the
      hypostome of a Hydra.
AB  - The numbers, types, and distributions of neurons in a hypostome of Hydra
      littoralis were determined from electron micrographs of serial (0.25 MUm thick)
      sections. In 1,080 serial sections examined we found 75 sensory cells and 949
      centrally located ganglion cells. More than 96% of the 1,024 neurons identified
      had a single cilium. Sensory cells were most numerous near the apex of the
      hypostome. Proceeding away from the apex, they steadily decreased in numbers; at
      120 MUm they were no longer observed. Ganglion cells were bimodally distributed;
      some were associated with sensory cells at the apex, but most were found at the
      sites of tentacle origin. We observed, throughout the hypostome, a total of 64
      neuronal clusters (three or more contiguous neurons), with an average of five and
      a maximum of 11 neurons in a cluster. Clusters were distributed similarly to
      ganglion cells: an initial concentration of clusters near the apex; the majority
      at the hypostometentacle junctions. Each neuron identified was traced through
      succeeding sections in which it was observed. We used a three coordinate system
      to create a three-dimensional reconstruction of the neuronal locations in the
      hypostome. Although the functional significance of the neuronal distributions we
      observed is unknown, we suggest that neurons at the apex of the hypostome
      transduce sensory information involved in feeding behavior. The neuronal
      concentrations at sites of tentacle origin may be responsible for initiating
      Contraction Burst Pulses associated with rhythmic behavioral patterns of Hydra or
      coordinating tentacle movements involved in prey capture, ingestion or
      locomotion.

PMID- 30111003
TI  - Buoyancy adaptations in a swim-bladderless Antarctic fish.
AB  - The endemic Antarctic teleosts of the suborder Notothenioidei are bottom
      dwellers. They lack swim bladders, are heavier than seawater, and feed on or near
      the bottom. The midwaters surrounding the Antarctic continent are productive and
      underutilized by fishes. There is an evolutionary trend toward pelagism in some
      notothenioids. We discovered that the largest Antarctic fish, Dissostichus
      mawsoni, was neutrally buoyant. Attainment of neutral buoyancy was associated
      with specializations of the skeletal, integumentary, muscular, and digestive
      systems. The skeleton had a low mineral content and contained considerable
      cartilage. Scales were also incompletely mineralized. Static lift was obtained
      from extensive lipid (mostly triglyceride) deposits. A 2-8 mm subcutaneous lipid
      layer accounted for 4.7% of the body weight. White muscle also contained much
      lipid-23% on a dry weight basis, or 4.8% of the body weight. Microscopic
      examination suggested that the liver was active in lipid metabolism, although it
      was not an organ of buoyancy. Stellate (perisinusoidal) cells with many lipid
      droplets were a very prominent cytological component of the liver. These
      specializations made Dissostichus neutrally buoyant and capable of inhabiting the
      food-rich Antarctic midwaters.

PMID- 30111004
TI  - An ultrastructural and fluorescence histochemical investigation of the
      innervation of retial arteries in Monodon monoceros.
AB  - In this study, the innervation of cerebrally related retial arteries in the
      narwhal Monodon monoceros was examined. Vessels were processed for the
      demonstration of adrenergic nerve endings by fluorescence histochemistry, and the
      results were confirmed by electron microscopy. Innervation of cerebrally related
      retial arteries was compared to that of a system situated in the haemal canal and
      supplying the tail. The retial arteries were poorly innervated. Adrenergic nerve
      endings, as indicated by fluorescence, occurred only in caudal portions of the
      spinal rete. Ultrastructurally, nerves were found in most retial vessels
      examined. However, except for arteries from caudal portions of the spinal rete,
      nerve numbers were few and because they occurred in outer layers of the
      adventitia were probably not functionally significant. In contrast, vessels in
      the haemal canal were well innervated. Nerve endings possessing neurotransmitter
      vesicles were adjacent to the smooth muscle cells. The cetacean rete mirabile, a
      system which supplies blood to the entire central nervous system, is apparently
      not under extensive nervous control, even though most reports suggest there is a
      relationship, possibly based on the presence of adjacent nerve trunks. Any
      vasomotor activity that does occur, possibly does so in response to
      catecholamines or other vasoactive agents circulating in the blood.

PMID- 30111006
TI  - An ultrastructural study of spermatogenesis in the nudibranch mollusc Spurilla
      neapolitana.
AB  - The ultrastructural features of spermatogenesis were investigated in the
      nudibranch mollusc Spurilla neapolitana. Sperm develop in the proximal half of
      numerous sac-like acini which are radially arranged within about ten ovotestis
      lobes. Accessory cells line the inner wall of the testicular portion of each
      acinus and are connected to developing sperm by numerous desmosomes. Stages of
      spermatid development have been divided into precup, cup, postcup, and elogate
      stages depending on the general shape of the nucleus. Nuclear differentiation
      includes the formation of anterior and posterior nuclear plaques, condensation of
      chromatin fibrils into nuclear lamellae, the insertion of the developing
      flagellar axoneme into a shallow, nuclear implantation fossa, and eventual
      formation of an elongated sperm head with a terminal twist. Spermiogenesis also
      includes the differentiation of an anterior, perinuclear structure having the
      characteristics of an acrosome, the appearance of peculiar arrays of ER
      cisternae, and the fusion of mitochondria into a large mitochondrial derivative
      which eventually encircles the axoneme, forming a crystalline-like periaxonemal
      sheath.

PMID- 30111005
TI  - Comparative analysis of the development of the lizard, Liolaemus tenuis tenuis.
      II. A series of normal postlaying stages in embryonic development.
AB  - In this work, we have completed a study of the development of the ovoviviparous
      lizard Liolaemus tenuis tenuis. Ovoviviparity in this lizard is a condition in
      which eggs are retained within the reproductive duct for about 60 days. During
      this period the phases of segmentation, gastrulation, neurulation, presomitic,
      and somitic embryos transpire. During the months of December and January the eggs
      are laid, and at this time the embryos are comparable to stage 27 Liolaemus
      gravenhorsti lizard embryos, or to stage 29 Calotes versicolor lizard embryos.
      Differentiation of the facial region occurs between Days 12 and 42 after egg
      laying. Limbs develop rapidly between the 8th and 23rd days. By 53 days the
      appendicular skeleton is completely formed. After 36 days the mesonephros begins
      to degenerate, and its function is gradually taken over by the developing
      metanephros. Newborn lizards do not possess an egg caruncle. During the period up
      to hatching, there is a great increase of liquid within the egg, presumably
      amniotic fluid. Cracks develop in the leathery shell shortly before hatching and
      are, perhaps, the first sign of the onset of hatching. Increase of liquid in the
      egg during postlaying development accounts for its increase in weight and change
      in shape. Weight of the embryo at hatching does not exceed 32% of the total
      weight of the egg.

PMID- 30111007
TI  - An electron microscopic study on the innervation of the gill filaments of a
      lamprey, Lampetra japonica.
AB  - This paper reports observations on the innervation of gill filaments of the
      lamprey, Lampetra japonica. Nerve fibers run on each side of the afferent
      filament artery (AFA nerve) and in the connective tissue compartment along the
      efferent filament artery (EFA nerve). The AFA nerve supplies vasomotor fibers to
      the afferent filament artery and arteriovenous anastomoses and special visceral
      motor fibers to branchial muscle fibers (musculus compressor branchialis
      circularis). Nerve endings of the vasomotor fibers contain large, cored vesicles
      (60-180 nm in diameter) with a variable number of small, clear vesicles (30-70
      MUm in diameter), whereas those of the visceral motor fibers have many small,
      clear vesicles with few large, cored vesicles. The EFA nerve supplies vasomotor
      fibers to the efferent filament artery. Their endings, containing mixtures of
      predominantly large, cored vesicles and small, clear vesicles make close synaptic
      contacts with reticular cells. The latter in turn are connected with each other
      or with smooth muscle cells in the wall of the efferent filament artery by
      nexuses. No nerves are found in the axial plate between the afferent and efferent
      filament arteries nor in the secondary lamellae of individual gill filaments. No
      afferent nerve supply to the gill filament has been found.

PMID- 30111008
TI  - Comparative limb myology of two opossums, Didelphis and Chironectes.
AB  - A comparative study of limb morphology indicates that the osteological and
      myological differences between Didelphis virginiana, the Virginia opossum, and
      Chironectes minimus, the water opossum, may be associated in Chironectes with
      decreased resistance to water and increased mechanical advantage of its muscles
      for increased force. Limb myology is described and a synonymy of terms is applied
      to the musculature of these two opossums.

PMID- 30111009
TI  - Carbohydrates in the webs of Argiope spiders.
AB  - Glycoproteins are present in the web of the orb-weaving spiders Argiope
      trifasciata and Argiope aurantia. Periodic acid-Schriff reactive glyco-proteins
      are confined in large part, to the sticky spiral and sticky spiral-radial
      junctions. Glycoproteins containing amino sugars appear associated with all
      fibers, especially the radial fibers. Enzymes may be used to remove glycoproteins
      selectively from the sticky spiral and stabilimentum.

PMID- 30111010
TI  - [Exploring research ideas of mechanism of dominant diseases in traditional
      Chinese medicine based on evidence-based medicine].
AB  - The prescription of clinical curative effect has promoted the formation and
      development of the dominant diseases in traditional Chinese medicine, but it has
      been controversial for a long time because its mechanism has not been effectively
      explained. Breaking the gap between animal/cell research and clinical research,
      and understanding the mechanism of dominant diseases in traditional Chinese
      medicine based on evidence-based medicine has become an important breakthrough in
      this scientific issue. Therefore, based on evidence-based medicine, we
      established the research concept that "originating from clinic, testing in
      experiment, returning to clinic". Taking the classic formula (Jinqi Jiangtang
      formula) treating diabetes as an example to find characteristic markers of
      diabetes supported by evidence-based medicine from clinic. We used the reverse
      analysis strategy of the response of characteristic markers to explore the
      intervention mechanism of Jinqi Jiangtang formula on characteristic markers.
      Then, we verified the key signaling molecules of the metabolic regulation of the
      Jinqi Jiangtang formula in clinic. The research ideas and key technologies for
      the mechanism of treatment of diabetes by Jinqi Jiangtang formula based on
      evidence-based medicine are formed, and it is expected to provide research
      reference for explaining the mechanism of dominant diseases in traditional
      Chinese medicine based on evidence-based medicine.

PMID- 30111011
TI  - [Advances in study of plant type III polyketide synthases].
AB  - Polyketides are a large class of natural products with notable structural
      diversity and different biological activities. They have essential
      pharmacological value for human health. In plants, the enzymes responsible for
      the formation of phenolic metabolites backbone structures are collectively known
      as type III polyketide synthases (PKSs), which are the key enzymes for the
      polyketides biosynthesis. The PKSs catalyze a series of condensation reactions of
      two-carbon acetate units with an acyl starter. A brief overview of this group of
      enzymes, including their reaction mechanisms, function modification, expression
      regulation, molecular evolution, and recent interesting findings are presented
      here.

PMID- 30111012
TI  - [Materiamedica literature study on medicinal properties and utility of four kinds
      of Alpinia Chinese medicines].
AB  - In order to explore the correlation between the medicinal properties,efficacy and
      application in the same genetic relationship,explain the scientific connotation
      of the medicinal properties and effects of traditional Chinese
      medicines(TCM),promote the academic development of the theory of traditional
      Chinese medicines,and provide reference for the research and development of the
      traditional Chinese medicines of a same genus. In this paper, a literature study
      of ancient and modern works of Chinese herbal medicine was conducted to
      investigate the correlation between the properties, meridians tropism, efficacy
      and application of Alpinia officinarum, A. katsumadai, Galangae Fructus and
      Alpinae Oxyphyllae Fructus, four kinds of Alpinia Chinese medicines.The results
      showed that the similar properties of these four kinds of Alpinia Chinese
      medicines included that they were acrid, warm,and mainly getting into the spleen
      and stomach channels; the similar efficacies included that dispelling
      cold,relieving pain,warming stomach,anti-nausea,anti-diarrheal,reinforcing spleen
      to promote digestion and other effects; in application aspects, the similarities
      were that they were all mainly used in treatment of catching cold or spleen
      deficiency induced by abdominal pain,vomiting,diarrhea,diet indigestion, etc.
      indicating that phylogenetic relationship was closely related with the herbal
      properties, efficacy and application. It is an effective way to explore,collate
      and research traditional Chinese medicine by using plant phylogenetic
      relationships in exploring the internal relations and laws of TCM
      theories,material bases, pharmacological effects and clinical applications, also
      with a strong maneuverability to explain their scientific connotation.

PMID- 30111013
TI  - [Effects of N and Zn interaction on growth, yield and active components of
      Agastache rugosa].
AB  - The study is aimed to explore the effect of combination use of nitrogen(N) and
      zinc(Zn) fertilizers on the growth, yield and the effective components of
      Agastache rugosa. A. rugosa was grown under two N application rate (120, 300
      kg.hm-2) and five Zn levels (0, 20, 50, 100,150 kg.hm-2) under field condition.
      The effect of the treatments on the physiological indicators, distribution of
      nitrogen and zinc and volatile oil components of A. rugosa were studied. The
      results showed that the combination use of N and Zn could significantly affect
      the growth and development, yield and volatile oil components of A. rugosa. Under
      the test conditions, the highest yield of Agastaches Herba was obtained when 50
      kg.hm-2 of Zn fertilizer was applied with high N application rate of 300 kg.hm-2.
      Under the same N application rate, the increase of Zn production was positively
      correlated with the amount of Zn application in a certain concentration range,
      but excessive Zn application led to the decrease of yield. With the increase of N
      application level, the content of Zn also significantly increased. The
      combination use of N and Zn increased the yield of Agastaches Herba. High level
      of N application was beneficial to the absorption and accumulation of N and Zn of
      A. rugosa. Zn fertilizer could also promote the absorption and accumulation of N
      of A. rugosa. The interaction between N and Zn had significant influence on the
      main chemical constituents of the volatile oil of A. rugosa. Among the volatile
      oil chemical constituents of A. rugosa the content of pulegone (34.56%-53.91%)
      and piperonyl methyl ether (18.86%-42.27%) were much higher. Under the same N
      application rate, different Zn application rates also had significant effects on
      the main chemical components of volatile oil.

PMID- 30111014
TI  - [Study on geographical variation of medicinal ingredients contents in Scutellaria
      baicalensis from different provenances].
AB  - In order to investigate the genetic difference on medicinal components of
      Scutellaria baicalensis from different provenances on the genetic difference, the
      S. baicalensis provenance tests were arranged by randomized block
      design.Excavating the crude drugs that have been growing for three years, with
      the same drying process, the content of baicalin, baicalein, wogonoside, wogonin
      and laminarin A in S. baicalensis were detected by HPLC, and then the data were
      analyzed. The results indicated that the content of baicalin in different
      provenances of S. baicalensis was significantly different (P<0.05), while the
      variation of baicalein reached extremely significant level (P<0.01). Cluster
      analysis showed that if the distance was divided by 5.0, the provenances in
      Chengde, Hebei province were divided into two independent populations, while the
      other two populations had large geographic spans. The results show that the
      significant geographical variations exist in the content of medicinal components
      in S. baicalensis. The study laid a theoretical foundation of provenance
      selection of S. baicalensis.

PMID- 30111015
TI  - [Effect of temperature on content of baicalin and expression of key enzyme genes
      in callus of Scutellaria baicalensis].
AB  - The study is aimed to explore the effect of different temperature on the content
      of baicalin and gene expression in the growth of Scutellaria baicalensis. Four
      culture temperatures were used to establish the callus culture of S. baicalensis
      under dark conditions for 40 days and once every 5 days. The growth and baicalin
      contents were determined. 18S RNA was used as a reference gene to analyze the
      five key factors in baicalin biosynthesis pathway (PAL), cinnamic acid 4
      hydroxylase (C4H), chalcone synthase (CHS), beta-glucuronidase (GUS), baicalein-7
      O-glucuronosyltransferase (UBGAT) gene expression levels. The results showed that
      biomass, baicalin content and accumulation increased with the increase of
      temperature. 25  degrees C and 30  degrees C were more suitable for the growth of
      S. baicalensis. The content and accumulation of baicalin at 25  degrees C reached
      the highest level at 30 days, reaching 2.75% and 12.44 mg, respectively. The
      relative expression levels of C4H, CHS, GUS and UGBAT genes at 15  degrees C were
      higher than those at other treatments. The correlation between the relative
      expression levels of each key enzyme and the content of baicalin was negatively
      correlated with the increase of incubation temperature. The relative expression
      levels of PAL, C4H and CHS genes at 25  degrees C and 30  degrees C were
      significantly correlated with the contents of baicalin and reached a highly
      significant or significant level. Relative low temperature conditions were not
      conducive to the growth of S. baicalensis and the accumulation of baicalin. The
      accumulation of baicalin by PAL and C4H in the upstream of the synthetic pathway
      was significant.

PMID- 30111016
TI  - [Geographical origin discriminant of Polygoni Multiflori Radix based on stable
      isotope ratios and elemental analysis].
AB  - The seventy samples of Polygoni Multiflori Radix were collected from three
      producing areas: Bozhou, Anhui province, Jingmen, Hubei province and Xichang,
      Sichuan province. Three stable isotope ratios and contents of 44 elements in the
      Polygoni Multiflori Radix samples were determined by EA-IR-MS and HR-ICP-MS.
      Three data mining methods,including partial least square discriminant analysis
      (PLS-DA), fisher linear discriminant analysis (FLDA) and decision tree CHAID were
      employed to establish a model for geographical origin discrimination.The study
      results showed that the stable isotope ratios expressed significant difference
      followed with the different producing areas, and will be used to discern the
      samples from different producing areas, effectively. Combined with the data of
      elemental analysis, the accuracy rates of model can be further improved. All the
      three methods showed the accuracy rates of external sample were over 90% using
      training dataset. These results confirmed that stable isotope ratios and multi
      elemental analysis combined with chemometric method was effectiv in geographical
      tracing of Polygoni Multiflori Radix.The analysis method has great potential and
      prospect in geographical origin discriminant of Chinese medicinal materials, and
      provids a new study method to identify origin information of Chinese medicinal
      materials.

PMID- 30111017
TI  - [Transcriptome analysis reveals candidate genes involved in flavonols
      biosyhthesis in Sophora japonica].
AB  - In order to study the pathways of biosynthesis of flavonoids in Sophora japonica,
      113 797 unigenes were obtained by Trinity software, with an average length of 803
      bp, of which 72 752 unigenes were obtained from the database by high-throughput
      sequencing, and a total of 38 891 SSR loci were searched. Through the metabolic
      pathway analysis, we found that there were 135 unigenes involved in the
      biosynthesis of flavonoids and 959 unigene involved in other secondary metabolic
      pathways. Further analysis of genes involved in rutin biosynthesis revealed that
      24 were associated with CHS, 52 were associated with FLS, and 11 were associated
      with UFGT. The obtained data of S. japonica transcriptome lays the foundation for
      studying the pathways of biosynthesis of flavonoids in S. japonica and provides
      theoretical basis for the formation of the quality of S. japonica.

PMID- 30111018
TI  - [Preparation of hispidulin chitosan microsphere and its antiproliferation effect
      in vitro].
AB  - Hispidulin(HPDL) chitosan microspheres were prepared in this study to deliver
      HPDL to the lesion sitevia intravenous injection, and further evaluate their
      anticancer effects in vitro and the growth inhibition effect on A549 cells
      spheroids. HPDL chitosan microspheres were prepared by emulsion crosslinking
      method with chitosan as a drug carrier and the amount of HPDL was determined by
      high performance liquid chromatography (HPLC). The morphology of microspheres was
      observed under laser scanning confocal microscope. Additionally, the drug release
      amount of targeting microspheres was detected by dialysis method. Furthermore,
      the anti-proliferative effects against A549 lung cancer cells were tested by
      sulforhodamine B (SRB) method, and the effects of HPDL chitosan micrpsphereson
      early apoptosis of A549 cellswere determined by flow cytometry. A549 cells tumor
      spheroids were developed in vitro and then HPDL chitosan microspheres were added.
      On the 0, 1, 3, 7 d after adding the drugs, the inverted microscope was used to
      observe the mythologicaland volume changes of A549 cells spheroids. The
      encapsulation efficiency of HPDL chitosan microspheres was (75.32+/-0.52)%, and
      the drug loading amount was (7.76+/-0.67)%. Meanwhile, the microspheres were
      round shaped andhad smooth surface. The HPDL chitosan microspheres exhibited
      stronger inhibitory effects on A549 lung cancer cells. The results of flow
      cytometry indicated that, the early apoptosis rate of lung cancer A549 cells was
      (37.0+/-0.75)% at 24 h cells culture after drug administration. The volume of
      tumor spheroid was significantly inhibited, which had been shrunk by (50.09+/
      11.06)% after the treatment by drug-loaded microsphere at day 7 as compared with
      blank group; meanwhile, the cells surface were obviously lysed. The preparation
      method in this research was simple and practicable, and the microspheres prepared
      with this method were round and smooth, with high encapsulation efficiency, which
      can significantly inhibit proliferation of lung adenocarcinoma A549 cells and
      induce cell apoptosis, and at the same time can cause lysisand death of A549 cell
      tumor spheroid.

PMID- 30111019
TI  - [Preparation optimization of extract of Moringa oleifera leaves and its immune
      regulation effect on immunosuppressed mice].
AB  - With total flavonoid content and dry extract yield as the observation indexes,
      the optimal extraction conditions of Moringa oleifera leaves were determined by
      using single factor test and orthogonal test, and cyclophosphamide modeling
      method was used to establish immunosuppressed mice models, so as to investigate
      the effects of M. oleifera leaves extract on immune regulation in mice. The
      results showed that the optimal preparation conditions were as follows:
      extraction with 70% ethanol, material-liquid ratio 1:15, extraction temperature
      80  degrees C, three times, 1.5 hours for each time. Under these conditions, the
      content of total flavonoids from M. oleifera leaves was 15.64 mg.g-1, which can
      significantly enhance macrophage phagocytosis and immune organ index, promote the
      synthesis of serum immunoglobulin IgG and hemolysin, and decrease AST activity,
      with regulation effect on immune dysfunction.

PMID- 30111020
TI  - [Study on dryness effect of Atractylodis Rhizoma based on theory of dry-dry and
      dryness-induced Yin deficiency].
AB  - In order to establish a more perfect evaluation system for dryness effect of
      Atractylodis Rhizoma, determine the main dry parts of Atractylodis Rhizoma,and
      further define the mechanism of stir-baked Atractylodis Rhizoma in reducing the
      dryness. The healthy rats were given with different doses of water extract and
      volatile oil of raw Atractylodis Rhizoma and stir-baked Atractylodis Rhizoma for
      21 days. Based on the theory of the dry-dry and dryness-induced Yin deficiency,
      the amount of drinking water, tissue morphology of submandibular glands, urine
      volume and the expression of aquaporin 2 (AQP2) in the kidneys, as well as blood
      rheology, ratio of cAMP/cGMP in serum and the content of Na+-K+-ATP enzyme were
      selected as the evaluation indexes. The results indicated that the rats with high
      dose volatile oil from raw Atractylodis Rhizoma had a significant increase in the
      amount of drinking water, urine volume, blood viscosity, ratio of cAMP/cGMP and
      content of Na+-K+-ATP enzyme in the serum(P<0.05)as compared with the soybean oil
      group; meanwhile, atrophy of submandibular acinar gland was obvious,and the
      expression of aquaporin 2 was reduced significantly(P<0.05). There were
      significant differences between volatile oil high dose group of raw Atractylodis
      Rhizoma and volatile oil high dose group of stir-baked Atractylodis Rhizoma.
      There was no significant difference between the water extract groups of raw and
      stir-baked Atractylodis Rhizoma and the saline group. A comprehensive evaluation
      system for the dryness effect of Atractylodis Rhizoma was established. It was
      confirmed that the volatile oil part was the main dry part of Atractylodis
      Rhizoma. It revealed that the mechanism of dryness effect of Atractylodis Rhizoma
      was not only related to the decrease of the total content of the volatile oil,
      but also may be related to the transformation of dryness components in the
      volatile oil. It provides references for the study of material basis of
      Atractylodis Rhizoma dryness, provides an experimental basis for the clinical
      application of Atractylodis Rhizoma, further clarifies the mechanism of stir
      baked Atractylodis Rhizoma in reducing the dryness, and provides thoughts for the
      evaluation of other dry traditional Chinese medicines.

PMID- 30111021
TI  - [Effect of anti-androgen and progesterone on development of regrowth antlers in 6
      year old sika deer].
AB  - To investigate the effects of anti-androgen drugs and melengestrol acetate (MGA)
      on development of regrowth antlers in 6 year old sika deer, twenty healthysika
      deerwith similar body weight and antler weightwere randomly divided into five
      groups by using single factor test design: flutamide (n=4), bicalutamide (n=4),
      progesterone acetate (CPA, n=4), melengestrol acetate (MGA, n=4), control(n=4).
      All deer were fed with same diets and were housed outside together in an opened
      fence of 15 m*30 m with free access to water and feed. Treatment groups were
      injected subcutaneously sustained-release agents of the four drugs respectively
      when two-branched antlers were harvested. The control group had no special
      treatment. In the experiment period of 60 d, blood sampleswere collected for 4
      times for each deer. The concentration of testosterone in plasma was tested and
      analyzed to compare the changes between different groups. Development of regrowth
      antlers was observed. At the end of the experiment, regrowth antlers were
      weighted and analyzed. The resultsshowed that the weights of regrowth antlers in
      treatment groups were significantly greater than those from control group and the
      weight gain (as compared with the control group) was 100.50%, 64.46%, 87.16% and
      117.46% respectively in flutamide group, bicalutamide group, progesterone acetate
      group and melengestrol acetate group. For plasma testosterone concentration, it
      was not significantly different in the early stage (in the first 35 d), but at
      the end of the experimen, it was significantly higher than that of earlier stage
      (P<0.01) in various groups. Testosterone concentration of flutamide treated group
      was significantly lower than that of the other groups (P<0.01), while the level
      inbicalutamide and MGA treated groups was significantly higher than that in other
      groups (P<0.01). The results showed that both anti-androgen drugs and MGA
      treatment promoted the development of regrowth antlers and increased the weight
      of regrowth antlers, where the effect was most significant by MGA treatment. From
      the morphological observation of the antlers, it was found that anti-androgen and
      MGA treatments prolonged the growth period of regrowth antlers through delaying
      the ossification of antlers. However, plasma testosterone concentration was not
      affected by the treatments.

PMID- 30111022
TI  - [Research and application of quality standard for standard decoction of
      Chrysanthemi Flos].
AB  - Standard decoction of traditional Chinese medicine (TCM) is prepared by
      standardized process, and can be used as references to evaluate the quality of
      dosage forms such as decoction and dispensing granules. In order to determine the
      quality evaluation method for standard decoction of Chrysanthemi Flos and
      investigate its application, 10 batches of white chrysanthemum of Hangzhou were
      collected to prepare the standard decoction of white chrysanthemum of Hangzhou
      with standardized process parameters. Parameters such as traits, relative
      density, pH value, extraction ratio, transfer rate and fingerprint were selected
      as the indexes for quality evaluation. The established quality evaluation method
      for standard decoction of Chrysanthemi Flos was applied in the detection of two
      types of commercial Chrysanthemum dispensing granules. The results showed that
      the standard decoction of Chrysanthemi Flos was a clear yellow-brown aqueous
      solution; the relative density was 1.007-1.011; the pH value was between 5.37
      5.56; the average extraction ratio was 23.6%, ranging from 19.93% to 29.69%; the
      average transfer ratewas 56.2% in terms of chlorogenic acid, 57.4% in terms of
      luteoloside and 30.6% in terms of 3,5-O-dicaffeoylquinic acid. Fingerprint
      similarity was between 0.864-0.989.The method showed good precision, stability
      and repeatability in fingerprint analysis, indicating reliable and representative
      results for standard decoction of Chrysanthemi Flos, and it can be used to
      evaluate and standardize other dosage forms.

PMID- 30111023
TI  - [Chemical constituents of Hypericum perforatum].
AB  - A chemical investigation on the aerial parts of Hypericum perforatum resulted in
      the isolation of a new phloroglucinol derivatives (1), and seven known compounds
      (2-8). The structures of the compounds were elucidated by means of spectroscopic
      methods (MS, IR, 1D NMR, and 2D NMR) as 3-methyl-4,6-di (3- methyl-2-butenyl)-3
      (4-methyl-3-pentenyl)-2-(2-ethyl-1-oxobutyl)-cyclohexanone (1),hyperforin
      (2),(2R,3R,4S,6R)-3-methyl-4,6-di(3-methyl-2-butenyl)-2-(2-methyl-1-oxo-propyl)-3
      (4-methyl-3-pentenyl)-cyclohexanone (3),hyperscabrin B (4),hyperscabrin C
      (5),furohyperforin isomer 1 (6),furoadhyperforin (7),and furohyperforin (8).
      Compound 1 was a new compound, and compounds 3-5 were obtained from H. perforatum
      for the first time.

PMID- 30111024
TI  - [Chemical constitutes from Clerodendrum japonicum].
AB  - The chemical constituents from the ethanol extract of Clerodendrum japonicum were
      isolated by a combination of various chromatographic techniques including column
      chromatography over silica gel, sephadex LH-20, ODS and reversed phase HPLC.
      Sixteen compounds with a pair of epimers were elucidated through the application
      of physicochemical properties with modern spectral analysis technology as 7alpha
      hydroxy syringaresinol (1), (-)-syringaresinol (2), (-)-medioresinol (3), 2",3"-O
      acetylmartyonside (4), 2"-O-acetyl-martyonside (5), martinoside (6), monoacetyl
      martinoside (7),cytochalasin O (8), 9-epi-blumenol B (9), (6R, 9S) and (6R,9R)-9
      hydroxy-4-megastigmen-3-one (10a,10b), (6R,9S)-3-oxo-alpha-ionol (11), (-)
      dehydrovomifoliol (12),megastigm-5-en-3,9-diol (13), (3R,6E,10S)-2,6,10-trimethyl
      3-hydroxydodeca-6,11-diene-2,10-diol (14), (2R)-butylitaconic acid (15), 3-(3&
      hydroxybutyl)-2,4,4-trimethylcyclohexa-2,5-dienone (16), (-)-loliolide (17), of
      which compound 1 and 15 are new natural product, the other compounds were
      isolated for the first time from Clerodendrum japonicum except for compounds 4, 6
      and 7.

PMID- 30111025
TI  - [Analysis on ecological factors and active components content of wild Dipsacus
      asper in Chongqing Wulong district].
AB  - An HPLC method was developed for the determination of iridoid glycosides (loganin
      acid, loganin, sweroside) and saponins (asperosaponin VI) in the wild Dipsacus
      asper. A total of 108 samples consecutive growing 12 month were collected in 9
      plots in Wulong district of Chongqing. Subsequent analysis of the content of
      loganin acid, loganin, sweroside and asperosaponin VI was performed by HPLC to
      evaluate the quality. In addition, 20 climate data provided by the world climate
      database (http://www.worldclim.org/) was analyzed to deduce the correlation
      between the growing environment factors and the active ingredient content
      accumulation of D. asperoides and choose the apposite growing environment for D.
      asper. The range of active ingredient content in wild D. asper were 0.01%
      3.80%(loganin acid), 0.08%-0.62%(loganin), 0.12%-0.78%(sweroside), 0.64%
      5.26%(asperosaponin VI). The highest content of these active ingredients was
      concentrated from February to April, with 2.64% of loganin acid, 0.36% of
      loganin), 0.57% of sweroside, and 3.09% of asperosaponin VI. The method used for
      determination of the active ingredient content in D. asper was simple and
      convenient with accurate result. The selection of the quadrats is scientific and
      reasonable and can be used for the analysis of the contents of the wild D. asper,
      thus provide a reference for quality evaluation of D. asper and protection of D.
      asper resources.

PMID- 30111026
TI  - [Synthesis and identification of artificial antigen of spinosin].
AB  - Immunogenic antigen (spinosin-BSA) and coating antigen (spinosin-OVA) of spinosin
      were synthesized by sodium periodate oxidation method. UV scanning analysis
      method showed that these two spinosins were successfully conjugated with carrier
      protein and the coupling ratio was 17 and 13.7, respectively. Meanwhile, when
      immunized by spinosin-BSA,the mice can produce anti-spinosin antibodies with the
      high titer (1:32 000),specificity (IC50 211.6 MUg.L-1) and low cross-reaction
      rate measured by ELISA tests. The artificial antigen of spinosin was successfully
      synthesized, which can be applied for preparation of monoclonal antibodies and
      establishment of appropriate immune method.

PMID- 30111027
TI  - [Effect of Xianling Gubao capsule on bone metabolism in ovariectomized rats].
AB  - To investigate the effect of Xianling Gubao capsule in preventing postmenopausal
      osteoporosis, forty-eight female Wistar rats were randomly divided into four
      groups: sham group (Sham), ovariectomized group (OVX), ethinylestradiol group
      (EE) and Xianling Gubao capsule group (XLGB). Rats in each group received
      ovariectomy, except for sham group. The XLGB group received Xianling Gubao
      capsule at the dose of 378 mg.kg-1.d-1. The dosage of EE group was 200 MUg.kg-1.d
      1, and OVX and Sham groups were only fed with equal volume of distilled water.
      All of the rats were put to death two months later. Bone mineral density, bone
      biomechanics, bone histomorphometry Micro-CT scanning and organ index of vital
      organs were calculated and pathologically observed. There was no significant
      difference in the body weight of rats and organ indexes of lung, kidney, heart
      and spleen in the experimental groups. There was also no significant change in
      their pathological observation, but the uterine index of OVX group and XLGB group
      was significantly lower than that of Sham group. According to the results of BMD
      test, compared with the OVX group, femurs and vertebrae BMD of the other three
      groups were increased, with statistically significant differences. On the basis
      of the results of bone biomechanical test, compared with OVX group, the maximum
      load values of femur and vertebrae of the other three groups were increased, with
      statistically significant differences, while the change of elastic modulus was
      not statistically significant. According to the bone histomorphometry results of
      VG staining, compared with Sham group, the number of trabecular bone was
      significantly lower than that in OVX group. Compared with OVX group, the number
      of trabecular bone in EE group and XLGB group was increased, but with no
      significant difference between EE and XLGB groups. The results of serum
      biochemical indexes showed that compared with Sham group, osteocalcin (OC)
      decreased, while tartrate resistant acid phosphatase 5b (TRACP 5b) increased in
      OVX group, with statistically significant differences. Compared with OVX group,
      the OC content of XLGB group and EE group increased, while the content of TRACP
      5b decreased, with statistically significant differences. On the basis of the
      results of Micro-CT scanning, the change trends of femur volume BMD, number of
      trabecular bone (Tb.N), trabecular bone thickness (Tb.Th), trabecular bone
      separation (Tb.Sp), bone volume/tissue volume (BV/TV) in the groups were
      consistent with those of bone histomorphometry. There was no significant change
      in femoral cortical bone between the two groups. Xianling Gubao capsule can
      prevent osteoporosis in ovariectomized rats. The possible mechanism is the dual
      activity of inhibiting bone resorption and improving bone formation.

PMID- 30111028
TI  - [Expression of oleosin-rhFGF9 fusion protein in Carthamus tinctorius and
      determination of hair regeneration and wound repair potential in mice].
AB  - The expression of fibroblast growth factor 9 (FGF9) recombinant fusion protein in
      Carthamus tinctorius was used to identify its effect on hair regrowth and wound
      repair system in mice, providing a basis for C. tinctorius as a plant bioreactor,
      and establishing a foundation for commercial applications of FGF9 fusion protein
      in hair regrowth and wound repair. The identified pOTBar-oleosin-rhFGF9 plasmid
      was transformed into Agrobacterium tumefaciens EHA105 by freeze-thaw method, and
      the oleosin-rhFGF9 gene was transformed into safflower leaves by A. tumefaciens
      mediated method. Transgenic safflower seedlings were then obtained by tissue
      culture. After basta screening, transgenic T3 safflower seeds were obtained by
      grafting method, PCR verification and propagation. The expression of oleosin
      rhFGF9 was detected by Western blot, and the content of oleosin-rhFGF9 fusion
      protein was 0.09% by using ELISA quantitative method. It was observed that 60
      MUg.L-1 transgenic safflower oil had better effect on promoting NIH/3T3 cells
      proliferation in a certain dose-dependent manner. Sixty C57BL/6 mice were used to
      establish alopecia model and wound model respectively, and then were randomly
      divided into control group (treated with PBS or saline), negative group (treated
      with wild type safflower seed oil bodies, 60 g.L-1), positive group (treated with
      FGF9, 0.054 g.L-1), low dose group (treated with transgenic safflower oil bodies,
      10 g.L-1) and high dose group (treated with transgenic safflower oil bodies, 60
      g.L-1). The skin of all above-mentioned mice models were coated with soft
      adhesive manner every other day, 100 MUL/time. After 15 days, the mice skin was
      cut and embedded for histological analysis. The hair regrowth experimental
      results showed that the hair of mice grew well, and the mice in high dose group
      had bushy hair, with significant effect on regeneration hair number as compared
      with the positive group. The healing was obvious in wound experiment, with
      significant healing effect in positive group, high dose group and low dose group
      as compared to blank control group. Furthermore, high dose group remarkably
      showed a better and higher healing effect than the positive group at day 5.
      Oleosin-rhFGF9 was successfully transformed into safflower, and T3 transgenic
      safflower oil bodies expressed oleosin-rhFGF9 fusion protein were obtained, with
      the role of promoting hair regeneration and wound repair in mice.

PMID- 30111029
TI  - [Mechanism of Duhuo Jisheng decotion in delaying degeneration of nucleus pulposus
      cells in human intervertebral disc].
AB  - This paper aimed to investigate the role of Duhuo Jisheng decotion (DHJSD) in
      delaying human disc degeneration and its possible molecular mechanism. The
      intervertebral disc specimens were divided into normal and degenerated groups
      according to Pfirrmann classfication. The expressions of TNF-alpha, IL-1beta, MMP
      3 and MMP-13 in intervertebral disc tissue were detected by Western blot and PCR.
      Then degenerated human primary NPCs were cultured in vitro, the viability of NPCs
      treated with stromal cell-derived factor-1 (SDF-1,10 MUg.L-1)and various
      concentrations of DHJSD was assessed by the CCK-8 assay, and the appropriate
      concentration was screened. The experiment was divided into three groups, control
      group, SDF-1 group and DHJSD plus SDF-1 group. The levels of TNF-alpha, IL-1beta,
      Agg, coIII, MMP-3 and MMP-13 were detected. The levels of CXCR4, NF-kappaB major
      groups P65 phosphorylation (p-P65) and nuclear translocation, after treated with
      CXCR4 siRNA and NF-kappaB inhibitor (BAY11-7082) were measured by Western blot
      and immunofluorescence. At the same time, the expression of cell inflammatory
      factors and extracellular matrix were also measured. The expressions of TNF
      alpha, IL-1beta, MMP-3 and MMP-13 in the degenerated intervertebral disc tissue
      were significantly increased. In vitro study, the results of CCK-8 indicated that
      the viability of NPCs was significantly increased when DHJSD concentration was
      300 mg.L-1. After the experiment was divided into three groups, compared with SDF
      1 group, the expressions of TNF-alpha, IL-1beta, MMP-3 and MMP-13 in DHJSD group
      were significantly decreased, but the expressions of Agg, coIII were
      significantly increased. When CXCR4-siRNA was transfected into NPCs, SDF-1
      increased expressions of CXCR4 and p-P65 and inhibited nuclear translocation of
      P65, whose effect was suppressed by CXCR4-siRNA and DHJSD. In addition, when
      BAY11-7082 was used to treat NPCs, the expression of TNF-alpha, IL-1beta, MMP-3
      and MMP-13 were significantly decreased. DHJSD could inhibit the production of
      inflammatory factors and promote the synthesis of extracellular matrix. The
      potential mechanism may be related to the SDF-1/CXCR4/NF-kappaB signaling
      pathway.

PMID- 30111030
TI  - [Anti-inflammatory mechanism of Dahuang Lidan Pian by network pharmacology].
AB  - Dahuang Lidan Pian contains Rheum palmatum, Gymnadenia conopsea and Phyllanthus
      emblica, which has a significant effect in the treatment of alcoholic fatty
      liver, cholestasis and cholecystitis. The efficacy of the formula in traditional
      Chinese medicine was clearing heat and promoting diuresis, removing dampness,
      detoxifying and relieving jaundice. These three herbs are widely used in the
      traditional Chinese medicine, Mongolian medicine and Tibetan medicine. Therefore,
      the formula was a representative subject in the researches for ethno-drugs. In
      this research, computer aided drug design methods were used to predict the action
      targets of the formula. Protein interaction network (PIN) was then constructed,
      and molecular complex detection (MCODE) clustering algorithm was used to obtain
      the modules of the formula, so as to analyze the potential action mechanism. The
      results showed that Rh. palmatum and P. emblica may have a synergistic protective
      effect on liver function by acting on analogous targets and pathways. G. conopsea
      regulated metabolic balance of nutrients to strengthen physical fitness. The
      research explained the liver-protecting mechanism of Dahuang Lidan Pian based on
      the PIN analysis on molecular network, which provides an reference for the
      further study of Dahuang Lidan Pian.

PMID- 30111031
TI  - [Mechanism of nephrotoxicity of rhubarb in rats].
AB  - The aim of this study was to investigate the renal toxicity of rhubarb and its
      mechanism. The SD rats were randomly divided into three groups: normal group and
      two rhubarb extract groups (16, 2 g.kg-1). According to the dose conversion
      method between human and animal, rhubarb 16 g.kg-1 and 2 g.kg-1 were equivalent
      to 10 times and 1.25 times of human clinical dose respectively. Rhubarb extract
      was administered by a gastric gavage to rats once daily for 30 days. Serum urea
      nitrogen (BUN), creatinine (CRE) and urine KIM-1, NGAL and renal morphology were
      analyzed. The expressions of OAT1, OAT3 and clusterin mRNA in kidney were
      measured. The results showed that the low dose of rhubarb had no obvious renal
      toxicity. The high dose group showed mild and moderate renal injury and a down
      regulation of clusterin mRNA expression in the kidney tissue. The renal toxicity
      in male animals was heavier than that in female animals. There was no significant
      change in blood BUN and CRE in the high dose group. But urine NGAL level of the
      high dose group increased by 51.53% compared with normal group, of which male
      animals increased more significantly (P<0.05, compared with the normal group).
      The expressions of renal OAT1 and OAT3 mRNA in the low dose group were obviously
      higher than that in the normal group. The results indicated that the high dose of
      rhubarb could cause the renal toxicity. The dosage should be controlled
      reasonably in the clinical use. OAT1 and OAT3 mRNA related to anionic transport
      in kidney tissue played a compensatory protective role in rhubarb-induced renal
      injury. But the compensatory effect is relatively weak at the high dose level. In
      addition, routine renal function indicators BUN and CRE had limitation for
      monitoring the kidney toxicity of rhubarb. It is suggested that urine NGAL
      detection might be helpful for monitoring the renal toxicity of rhubarb.

PMID- 30111032
TI  - [Effect of serum containing Xihuang pill on proliferation of human breast cancer
      cell line MDA-MB-435 and MCF-7 Cells].
AB  - To study the effect of serum containing Xihuang pill on the proliferation of
      human breast cancer cell lines MDA-MB-435 and MCF-7 and the gene and protein
      expressions of Bcl-2, Bax, TP53, in order to explore the effect and mechanism of
      Xihuang pill in resisting breast cancer. The serum of the rats was prepared by
      the method of MTT assay. The expressions of Bcl-2 and Bax were detected by RT
      PCR. The serum levels of Bcl-2 and Bax and the mRNA expression of TP53 were
      detected by immunofluorescence. The rats with serum containing Xihuang pill could
      inhibit the proliferation of MDA-MB-435 cells and MCF-7 cells (P<0.05). The serum
      containing Xihuang pill increased TP53 and Bax in MDA-MB-435 cells (P<0.05), and
      the ratio of Bcl-2/Bax was decreased (P<0.05). Meanwhile, the serum containing
      Xihuang pill could up-regulate the mRNA expression of Bax in MCF-7 cells and
      decrease the expression of Bcl (P<0.05), but there was no significant difference
      between the expression of TP53mRNA and Bax protein expressions after the
      treatment of MCF-7 cells with Xihuang pill serum. Serum containing Xihuang pill
      can induce the apoptosis of human breast cancer cells, and the mechanism of
      estrogen receptor-negative breast cancer cell apoptosis may be induced by up
      regulating the mRNA expression of TP53, which can induce the expression of Bax
      and promote the metastasis of Bax to mitochondria, and ultimately play the role
      of inducing apoptosis.

PMID- 30111033
TI  - [Preclinical study on adverse reactions of Xingnaojing injection].
AB  - In this study, different batches of Xingnaojing injection products were first
      selected for pseudoallergic mice test, and the results showed that after
      injection of 6.6-fold clinical dose Xingnaojing injection, the mice showed a
      slight pseudoallergic reaction, while other mice injected with other batches of
      injections showed no obvious pseudoallergic reaction. Therefore, it is
      preliminarily believed that this mice model can effectively indicate the risk of
      pseudoallergic reactions in the clinical application of Xingnaojing injections.
      In addition, by changing some of the processes, a high concentration of
      Xingnaojing injection was prepared for mice pseudoallergic test and guinea pig
      systemic allergy test. The results showed no significant type I allergic reaction
      in guinea pigs. Mild pseudoallergic reactions occurred in mice after a 6.6-fold
      clinical dose injection. Therefore, it is considered that for sensitive or
      idiosyncratic people, the concentration of certain chemical components in
      Xingnaojing injection will increase after entering the body, which may increase
      the risk of pseudoallergic reaction. However, due to the limitations of test
      models, the risk of Xingnaojing injection to induce allergic reactions cannot be
      ruled out. Finally, by increasing the content of borneol and Tween and (or)
      sodium chloride in Xingnnaojing Injection and testing its pseudoallergic
      reactions, the results showed that the combination of these three ingredients may
      produce new trace sensitization substance and induce pseudoallergic reactions.

PMID- 30111035
TI  - [Tripterygium glycosides in treatment of henoch-schonlein purpura nephritis: a
      systematic review of randomized controlled trials].
AB  - To evaluate the clinical efficacy and safety of tripterygium glycosides (TG) in
      the treatment of henoch-schonlein purpura nephritis(HSPN). Seven English and
      Chinese databases (up to Nov. 9, 2017), were searched to collect the RCTs on TG
      for HSPN. Two researchers independently screened the literature according to
      inclusion criteria and exclusion criteria, extracted data, and evaluated the
      quality of the literature. After completion, cross-checking was performed and
      Meta-analysis was performed using RevMan 5.3 software. At the same time,
      different outcomes of the interventions were analyzed subgroupically. A total of
      46 RCTs were included, with 1 659 in the experimental group and 1 596 in the
      control group. All the clinical studies showed a low quality. In terms of
      complete remission rate, the group with TG performed better than the group with
      conventional therapy or GC(RR=1.82,95%CI[1.39,2.39];RR=2.03,95%CI[1.37,2.99]),the
      group with TG+GC performed better than the group with
      GC(RR=1.46,95%CI[1.32,1.60]),and the group with CTX+GC performed better than the
      group with TG+GC(RR=0.35,95%CI[0.16,0.75]). In terms of total effective rate, the
      group with TG performed better than the group with conventional therapy or
      GC(RR=1.44,95%CI[1.19,1.74];RR=1.30,95%CI[1.16,1.46]),the group with TG+GC
      performed better than the group with GC(RR=1.27,95%CI[1.21,1.34]),and the group
      with CTX+GC performed better than the group with TG+GC(RR=0.60,95%CI[0.43,0.85]).
      No significant difference was found between the group with TG+GC and
      LEF+GC(RR=0.68,95%CI[0.30,1.53]). In terms of urinary protein, urine occult blood
      negative time,the group with TG performed better than the group with conventional
      therapy(MD=-9.00,95% CI[-11.99,-6.01];MD=-12.00,95%CI[-16.13,-7.87]),the group
      with TG+GC performed better than the group with GC(MD=-8.86,95%CI[-10.08,
      7.64];MD=-16.24,95%CI[-23.80,-8.67]). In terms of recurrence rate, the group with
      TG+GC was lower than the group with GC(RR=0.13,95%CI[0.06,0.25]), but there were
      no significant difference between the group with TG and conventional
      therapy(RR=0.43,95%CI[0.15,1.19]). In adverse reactions, the common adverse
      effects of TG were gastrointestinal discomfort, liver damage and leucopenia. TG
      for the treatment of HSPN can improve clinical efficacy, reduce recurrence, and
      the adverse reactions are relatively safe. Due to the generally low
      methodological quality of the included studies, which affected the accuracy and
      reliability of the result. Therefore, more high-quality, large samples and multi
      center randomized controlled trials are necessary for further evidence.

PMID- 30111034
TI  - [Studies on constituents of Polygonum multiflorum extract in vivo and in vitro
      based on UPLC-Q-TOF-MS].
AB  - To explore the drug-induced constituents in vivo of Polygonum multiflorum extract
      (PM). This study was the first to study the drug-induced constituents in target
      organ liver. Agilent MassHunter qualitative analysis software and Metabolite ID
      software were applied for the analysis of retention time, exact relative
      molecular mass, primary and secondary mass spectrum information based on ultra
      performance liquid chromatography-quadrupole time-of-flight mass spectrometry
      (UPLC-Q-TOF-MS) and targeted-MS/MS. By comparison with literature and standards,
      a total of 5 prototypes and 6 metabolites were identified or tentatively
      elucidated from the liver samples. In addition, the drug-induced constituents in
      plasma and PM were also analyzed in this study and 8 prototypes and 19
      metabolites were detected from the plasma samples, while 30 compounds were
      detected from the extract of PM. Emodin oxidative acetylation metabolites,
      hydroxyl methylation metabolites, carboxylation glucuronidation metabolites and
      ketone glucuronidation metabolites in this study were first reported. Through the
      comparative analysis between the in vivo and in vitro constituents of PM, the
      study preliminarily revealed the drug-induced constituents (prototypes and
      metabolites) in liver and clarified the transfer process and transmutation rules
      of constituents in PM, blood and liver, which would further deepen our
      understanding on constituents of PM in vivo.

PMID- 30111036
TI  - [Analysis of traditional Chinese medicine prescriptions based on support vector
      machine and analytic hierarchy process].
AB  - Combined use of drugs is a hot spot in the research of new drugs nowadays, and
      traditional Chinese medicine (TCM) is a classic practice in the combined use of
      drugs. In this paper, the compatibility of TCM prescriptions and the related
      properties of composed herbs were calculated and studied to verify and discuss
      the feasibility of the results in guiding compatibility. Research Group on New
      Drug Design, Institute of Chinese Materia Medica, China Academy of Chinese
      Medical Sciences had established a structured database of TCM prescriptions by
      using traditional Chinese medicine inheritance support system (TCMISS V2.0),
      including 4 012 prescription compatibilities, 2 072 drug components, 381 kinds of
      TCM diseases, 316 kinds of TCM syndromes and 26 kinds of drug properties. On the
      basis of the created database above, Support Vector Machine (SVM) was used to
      analyze the prescription compatibility data and establish a model for predicting
      feasibility of drug compatibilities. Analytic Hierarchy Process (AHP) and cluster
      analysis were used to study the influence of drug properties in the rationality
      of prescription compatibility. The computational results showed that the accuracy
      in efficacy prediction of two data sets, i.e. prescription-disease and
      prescription-syndrome, was up to 90% in the linear SVM model. The macro-averaging
      and micro-averaging of the two models were around 0.92, 0.46, respectively. After
      AHP mapping, most of the incompatible combinations showed significant difference
      with other drug combinations during the clustering process in the vertical
      icicle, indicating that the proper machine learning algorithm can be used to lay
      the foundation for further exploring the combination rules in TCM and
      establishing more detailed drug-disease and syndrome predicting models, and
      provide theoretical guidance for the study of the combined use of drugs to a
      certain degree.

PMID- 30111037
TI  - [Analysis on mechanisms and medication rules of herbal prescriptions for gout
      caused by heat-damp accumulation syndrome based on data mining and network
      pharmacology].
AB  - To mine the medication rules of herbal prescriptions for gout caused by heat-damp
      accumulation syndrome, and explore the possible mechanism of the core herbs, we
      collected the relevant literature of gout caused by heat-damp accumulation
      syndrome in CNKI, medication rules of herbal prescriptions are analyzed by using
      TCMISS(V2.5) software, and the compatibility of core drugs and new prescriptions
      were mined.KEGG pathway analysis was performed by BATMAN-TCM, an online analysis
      tool, and the potential signaling pathways of core drugs compatibility to treat
      gout caused by heat-damp accumulation syndrome were revealed. The results showed
      that six core drugs and three new prescriptions were found out of the 136
      prescriptions. The core compatibility herbs in clinical treament of gout caused
      by heat-damp accumulation syndrome, Phellodendri Chinrnsis Cortex, Achyranthis
      Bidentatae Radix and Achyranthis Bidentatae Radix, which potential signaling
      pathways were purine metabolic pathway and neura activity ligand receptor
      interaction signaling pathway. Therefore, for gout caused by heat-damp
      accumulation syndrome, the mainly used therapies of TCM were clearing heat and
      drying dampness,inducing diuresis for removing edema, dispeling wind and
      eliminating dampness. The mechnisms of core compatibility herbs may be achieved
      through the intervention of purine metabolic pathway and neural activity ligand
      receptor interaction signaling pathway.

PMID- 30111039
TI  - [Standardization system of industry decoction pieces based on whole process
      quality control concept].
AB  - Traditional Chinese medicine (TCM) decoction pieces refer to prescription drugs
      that can be used in clinical or preparation production after processing medicinal
      herbs. TCM decoction pieces industries are inherited from the culture of TCM and
      are important because of their independent intellectual property rights. The
      Chinese Pharmacopoeia (Ch. P) 2010 edition stipulated that "All drugs taken are
      decoction pieces", which raised the drug status to statutory law for the first
      time and clearly specified that TCM decoction pieces should be applied to TCM
      prescription deployment and production of proprietary Chinese medicines. It also
      pointed out that "The specifications of the decoction pieces used in the
      preparation should comply with the requirements of the actual process of the
      corresponding formulation type". For a long time, both the processing methods and
      the specification grades of the clinically used pieces of Chinese medicine were
      based on the inheritance and supported by the classical theory and method system
      centered on TCM processing. However, the theoretical research and specification
      standards of the decoction pieces used in the production of proprietary Chinese
      medicines based on modern industry are scarce, and this has led to a series of
      problems related to the industry, making the processing of decoction pieces
      becoming a limiting factor in the promotion of the Chinese medicine industry.
      Aiming at the existing problems of the TCM decoction pieces industry, this
      article was guided by the standardization system of TCM based on the concept of
      whole-process quality control, combined with the reference to the Japanese Kampo
      medicine industry's feeding mode and the reflection on the combination of
      traditional Chinese medicine processing and modern industry, as well as the study
      of the core law of the whole-process of TCM production, etc. Industrial decoction
      pieces and the idea of building a standardized system of TCM industry decoction
      pieces based on the whole-process quality control were discussed in this paper,
      which can provide insights for exploring the effective fusion between TCM
      processing theory and classic heritage and modern manufacturing and can provide
      the basis for the establishment of a standardized system for industrial decoction
      pieces based on whole-process quality control of TCM. It can also offer reference
      for the development of the advantages of geo-authentic crude drug and the
      establishment of high spots of industry decoction pieces.

PMID- 30111038
TI  - [Status of Polygonati Rhizome industry and suggestion for its sustainable
      development].
AB  - Field surveys and literatures show that Polygonati Rhizome (Huangjing) was
      firstly recorded in Shen Nong&s Herbal Classic, and widely used as a medicinal
      and edible plant. It has a long history of cultivation, and the researches on
      chemistry have made some progress. The future development is prospected on health
      market. But the Polygonati Rhizome industry has faced a lot of problems,
      including the resource depletion, unstable quality, low-tech in cultivation and
      germplasm confusion, unclear of functional composition, decentralized, small
      scaled and primary processing products. The suggestion for sustainable
      development are listed below. First, the relevant researches should focused on
      material basis and biological mechanism of core effects. To speed up the
      selection and breeding of improved varieties, ensure the supply of high-quality
      seedlings and eliminate the unauthentic species are the most important measures.
      Secondly, to strengthen the conservation and rational use of wild resources,
      break through the key technologies of high-quality artificial cultivation on
      light regulation, site control, density control and precision harvesting are also
      very important. Thirdly, to reveal the toxicity-reducing-and-efficacy-enhancing
      mechanism of processing, optimize the parameters and setup the standard operating
      procedure are indispensable. Fourthly, that full advantage of the root, leaf,
      flower and fruit resources should be strengthened for enlarged health products
      based on the development of exact functional factors. Above all, Polygonati
      Rhizome could be a growing market in the future driven by the technological
      innovation, cultural creativity, integration of three industries, brand strategy
      and internet+technique.

PMID- 30111040
TI  - [Background and overall design of Chinese medicine resources assessment].
AB  - This paper comprehensively analyses the background and meaning of The
      Technological Guiding Principle for Assessment of Chinese Medicine Resources
      enacted by the former CFDA ( China Food and Drug Administration), moreover, it
      also points out that the Chinese medicine resources assessment with the purpose
      of guaranteeing the sustainable supplying capacity of Chinese medicine resources
      is the premise of new drug development; the Chinese medicine resources assessment
      which takes quality guarantee as the core is a significant action to promote the
      fixing of place of origin and quality-management antedisplacement for the
      traditional Chinese medicine industry; in this regard, the Chinese medicine
      resources assessment which aims at realizing the whole-process traceability is
      the key to building the high-quality modern traditional Chinese medicine brand.
      The Chinese medicine resources assessment which takes the classical prescription
      as the entry point is the embodiment of the protection of traditional Chinese
      medicine resources and international vision of regulation, which aims at
      clarifying the thinking for the relevant enterprises to carry out the Chinese
      medicine resources assessment. Base on the general thinking of ensuring that the
      "total amount of Chinese medicine resources is fixed and the supply is
      guaranteed", this paper clarifies two methods of Chinese medicine resources
      assessment: "family property assessment" of Chinese medicine resources based on
      "fixed total amount", "supply and demand balance assessment" of Chinese medicine
      resources based on "supply guarantee". In this regard, the basic strategy of
      "supply and demand balance assessment" of Chinese medicine resources based on
      "guaranteed supply" is put forward and it is believed that the resources
      assessment will lead to the significant adjustment of traditional Chinese
      medicinal materials production. It becomes the only way for the development of
      various Chinese medicine production enterprises to realize the comprehensive
      improvement of Chinese medicine quality, brand construction, the establishment of
      preferential price mechanism.

PMID- 30111041
TI  - [Comparative study on contents of four alkaloids in homologous herbal medicines-
      Arecae Pericarpium and Arecae Semen].
AB  - To establish a high performance liquid chromatography (HPLC) method for
      simultaneous determination of four alkaloids(arecoline, guvacoline, arecaidine,
      and guvacine) in Arecae Pericarpium (AP) and Arecae Semen (AS), and compare the
      contents of these four alkaloids between different medicinal parts. The
      chromatographic conditions were as follows:Welch SCX(4.6 mm*250 mm, 5 MUm)column,
      with acetonitrile-0.2% phosphoric acid solution (adjusted to pH 3.85-3.90 with
      ammonium hydroxide) at 50:50 as the mobile phase, at a flow rate of 0.5 mL.min-1.
      The column temperature was set at 35  degrees C, and the detection wavelength was
      215 nm. The results of content determination in 7 batches of AS and 10 batches of
      AP showed that, the contents of 4 alkaloids in AS (arecaidine 0.020%-0.045%,
      guvacine 0.031%-0.086%, arecoline 0.194%-0.346%, and guvacoline 0.065%-0.094%)
      were generally higher than those in AP (arecaidine 0.10%-0.032%, guvacine 0.006%
      0.029% arecoline 0.00%-0.070%, and guvacoline 0.00%-0.020%), and most of the APs
      had no arecoline and arecaidine at all in fruit peel. The above results indicated
      that different alkaloids can be used to distinguish the different medicinal parts
      of Arera catechu. Arecoline, guvacoline, arecaidine, and guvacine can be used as
      the quality control markers of AS, while for AP, only arecaidine and guvacine
      were needed.

PMID- 30111042
TI  - [Determination of salvianolic acid B and borneol in compound Danshen tablet by
      near-infrared spectroscopy and establishment of dependency model].
AB  - To determine the contents of salvianolic acid B and borneol in compound Danshen
      tablet (composed of Salviae Miltiorrhizae Radix et Rhizome, Notoginseng Radix et
      Rhizome and Borneolum Syntheticum) by near-infrared spectroscopy (NIR) and to
      establish a dependency model for rapid quantitative analysis. NIR data of 74
      batches of compound Danshen tablet from different companies were collected; the
      contents of salvianolic acid B and borneol were determined by using high
      performanceliquid chromatography (HPLC) and gas chromatography (GC) respectively
      to establish the dependency model for salvianolic acid B and borneol. The results
      showed that the best waveband for salvianolic acid B was 10 846.2-10 013, 9 195.3
      8 362.2, 6 719.1-4 242.8 cm-1; root-mean-squares error of cross-validation
      (RMSECV), coefficient of determination R2 and regression point displacement (RPD)
      of salvianolic acid B were 1.72 mg.g-1, 91.05% and 7.93 mg.g-1, respectively.
      While the best wavebands, RMSECV, R2 and RPD of borneol were 10 846.2-5 060.5 cm
      1, 1.2 mg.g-1, 96.11% and 6.71 mg.g-1,respectively. The relative error of the
      established model as validation results for validation set samples was 2.67% and
      4.64%, respectively.With the good predictability, the models can be applied to
      the real time monitoring and quality control of compound Danshen tablet.

PMID- 30111043
TI  - [Study on quality control method of toad venom based on characteristic
      chromatogram and QAMS].
AB  - Toad venom (Chansu) is prepared from the dried secretion of parotid gland and
      skin gland from Bufo bufo gargarizans or B. melanostictus. Up to now, much
      attention shall be paid to the poor quality of commercial toad venom because of
      the adulteration. So, it is urgent to establish a scientific and perfect quality
      control method to improve the quality of toad venom and guarantee its safety and
      effectiveness in clinical application. The different batches of toad venom
      samples were assayed by high performance liquid chromatography (HPLC) and the
      quantitative analysis of multi-components by single marker (QAMS) was used to
      detect the contents of five bufagenins. As a result, the reference characteristic
      chromatogram was established, displaying serotonin, gamabufotalin, arenobufagin,
      hellebrigenin, telocinobufagin, bufotalin, cinobufotalin, bufalin, cinobufagin
      and resibufogenin as characteristic peaks. Taking cinobufagin as an internal
      reference substance, QAMS was verified for the determination of five bufagenins
      (gamabufotalin, bufotalin, bufalin, cinobufagin, resibufogenin) in toad venom
      samples. The durability and applicability of the relative correction factor (RCF)
      were also studied systematically. RCFs of cinobufagin to gamabufotalin,
      bufotalin, bufalin and resibufogenin were determined as 1.05, 0.895, 1.09 and
      0.913, respectively. The characteristic chromatogram and QAMS established in this
      study could effectively control the quality of toad venom and provide scientific
      evidence for the improvement of the quality standard of the toad venom to be
      described in Chinese Pharmacopoeia (2020 edition).

PMID- 30111044
TI  - [Structural identification of related substances in Breviscapine by UPLC-QTOF
      MS].
AB  - To systematically identify the related substances in the original materials of
      breviscapine injection, 18 batches of samples collected from different
      pharmaceutical companies, its ethanol extract and breviscapine mother liquor
      concentrate were analyzed by high performance liquid chromatography (HPLC), and
      their structures were identified by ultra performance liquid chromatography and
      quadruple/time-of-flight mass spectrometry (UPLC-QTOF-MS). Under the selected
      chromatographic conditions, scutellarin and related substances have good
      resolution and 13 related substances were observed. Based on the molecular weight
      and fragmentation patterns obtained by UPLC-QTOF-MS as well as reference
      substances, their structures were elucidated as 6-hydroxyapigenin-6-O-glucosyl-7
      O-glucuronide (1), 5,7,8,3',4',5'-hexahydroxyflavone-7-O-glucuronide (2),
      5,6,7,3',4'-pentahydroxyflavone-7-O-glucuronide(3)and its isomer (4), patuletin-3
      O-glucuronide (5), methoxylscutellarin (6), apigenin 7-O-glucuronide (7),
      isorhamnetin 7-O-glucuronide (8), diosmetin 7-O-glucuronide (9), scutellarein
      (10), scutellarin methyl ester (11), scutellarin ethyl ester (12), and apigenin
      (13). This study has clarified related substances in the original materials of
      breviscapine injection, providing references for the improvement of quality
      control for breviscapine drug material and its preparations.

PMID- 30111045
TI  - [HPLC fingerprint of Zishen Yutai pills and simultaneous determination of 5 index
      components].
AB  - To establish the HPLC fingerprint and determine five index components (loganic
      acid, chlorogenic acid, loganin, sweroside and asperosaponin VI) of Zishen Yutai
      pills by high performance liquid chromatography, and provide a scientific basis
      for its quality control. The fingerprint chromatogram was analysed by the
      chromatographic fingerprint similarity evaluation system for tradition Chinese
      medicine (2012), fifteen common peaks were obtained at the wavelength of 254 nm.
      Different batches of Zishen Yutai pills showed a similarity of above 0.90 in HPLC
      fingerprint profiles. For the quantitive analysis method, The separation of five
      components showed good regression (r>0.999 2) with linear ranges, and the mean
      recoveries were in the range of 97.62%-101.9%, with the RSD (n=9) less than 3%.
      The established fingerprint and quantitative analysis methods are highly
      specific, simple and accurate, which can reflect the quality of Zishen Yutai
      pills more comprehensively, and can be used for its quality control.

PMID- 30111046
TI  - [Research progress of chemical components and pharmacological effects of non
      medicinal parts of Crocus sativus].
AB  - The dried stigma of Crocus sativus (saffron) is a world&s precious spice and
      traditional medicine possessing plenty of pharmacological effects. Because the
      stigma represents only 7.4% of total weight of the fresh flower, when the stigma
      is separated from the flowers, large quantities of floral bio-residues are
      discarded. Accordingly, the utilization of the non-medicinal parts of saffron has
      drawn people&s attention. Studies showed that the non-medicinal parts of saffron
      were rich in flavonoids, phenolic acids, polysaccharides, et al. They were proved
      to have some pharmacological activities, such as antioxidant activity, antifungal
      activity, cytotoxicity, anti-inflammation and liver protection. The paper is to
      review the current research progress on the chemical components and
      pharmacological effects of the non-medicinal parts of saffron, which can serve as
      a reference for the further research and development of non-medicinal parts of
      saffron.

PMID- 30111047
TI  - [Research progress on pharmacological effects of separation and combination
      methods based on traditional Chinese medicine property and flavor].
AB  - The theory of medicinal properties of traditional Chinese medicine (TCM) is one
      of the core theories of TCM, which is an important basis for guiding the clinical
      application of TCM and the key supporting point for the modernization of TCM. How
      to study the modernization of TCM under the guidance of traditional Chinese
      medicine theory has become a great challenge for modern researchers. Currently,
      the researches in TCM mainly focus on chemical studies such as on active
      ingredients and effective components, lacking the guidance of traditional Chinese
      medicine theory, and losing the inherent characteristics of TCM. Therefore, the
      combination of the theory of TCM and the modernization of TCM and the
      establishment of research mode that is in line with the characteristics of
      modernization of traditional Chinese medicine under guidance by the theory of
      medicinal properties of TCM shall be the top priority in modern Chinese medicine
      research. The property and flavor of TCM are closely related to its chemical
      compositions, and also have certain regularity. The researches on the chemical
      components of TCM, systematic design of property and flavor, as well as the
      separation and combination of TCM property and flavor are beneficial to the
      overall analysis of the characteristics of TCM, showing great significance to
      inherit and carry forward TCM. The pharmacological effects about separation and
      combination methods based on TCM property and flavor were reviewed in this study,
      providing theoretical reference for the development of new drugs and the
      application of TCM.

PMID- 30111048
TI  - [Morphological, microscopic, multiple-component assay and fingerprinting based
      systematic research on quality evaluation of Moutan Cortex(Paeonia
      suffruticosa)].
AB  - The purpose of this study was to combine morphological, microscopic, UHPLC
      multiple-component assay and fingerprinting studies in order to evaluate the
      quality of Moutan Cortex (MC) systematically. The root system of Paeonia
      suffruticosa was measured to compare the morphological variation and the chemical
      composition of different grades of MC was discussed according to previous
      studies. The difference between the main microscopic features of MC powder and
      the xylem powder is dramatic, the MC powder contains great amount of starch
      granules and clusters of calcium oxalate, while the xylem powder displays
      considerable vessels. Interestingly, the growth rings of P. suffruticosa was
      first reported in the xylem of the root transection, this can help to determine
      the growth years of the plant. Moreover, through the assay of 16 component, MC
      produced in Tongling and Bozhou in Anhui province were compared, content of PGG
      in MC produced in Bozhou was significantly higher than MC produced in Tongling
      (P<0.01). MC with different growth years, MC with xylem and unprocessed MC and MC
      decoction pieces were compared respectively by combining the results of 16
      compounds assay and fingerprinting. It is proposed that the quality evaluation
      standard include the assay of paeoniflorin. Above all, the holistic quality
      difference can be evaluated more comprehensively by combining multiple analytical
      methods.

PMID- 30111049
TI  - [Comparative study on content of heavy metals in Chrysanthemum indicum and soil
      in different areas].
AB  - ICP-MS was used to determine the contents of five heavy metals such as lead (Pb),
      cadmium (Cd), mercury (Hg), arsenic (As) and copper (Cu) in Chrysanthemum indicum
      and soil samples. Pearson correlation and path analysis were used to analyze the
      effects of latitude and longitude and altitude on the content of heavy metal
      elements in Ch. indicum. To explore the relationship between geographical
      location of heavy metal content in Ch. indicum and the content of heavy metal
      elements in soil. The results showed that the Ch. indicum had high enrichment of
      Cd and had a synergistic effect on the absorption of five heavy metal elements.
      Elevation directly affected the accumulation of Pb and Cd in Ch. indicum and was
      a positive effect. The direct positive effect of latitude acts on the
      accumulation of Hg and Cu in Ch. indicum. The effect of longitude on the Cd
      content was the negative effect of longitude. The geographical location had
      different effects on the accumulation of heavy metal elements in Ch. indicum.
      There was a certain interaction between direct and indirect effects. Ch. indicum
      had different absorption and enrichment characteristics for different heavy metal
      species. When controlling the heavy metal content and medicinal material quality
      of Ch. indicum, we must fully consider the influence of geographical location on
      the quality of medicinal materials, select suitable geographic regions to carry
      out acquisitions, and choose a good ecological environment. Regional
      establishment of Chinese herbal medicine planting bases, or adopting certain
      agricultural measures to reduce the absorption of heavy metal elements in Ch.
      indicum herbs, while conducting research on chemical composition, strengthening
      the research on the effective forms of heavy metals, and paying attention to the
      safety of medicinal herbs.

PMID- 30111050
TI  - [Gray mold disease of Paris polyphylla var. yunnanensis and its pathogen
      identification].
AB  - Gray mold disease is one of the most important diseases of planted Paris
      polyphylla var. yunnanensis, the disease appeared primarily as blossom blights
      and fruit rots, but also as stem rots, leaf rots.In this study, the pathogenetic
      fungi was isolated from plant tissue or sclerotia that covering the fruit of
      diseased P. polyphylla var. yunnanensis, the pathogen was certified according to
      Koch's Postulation. The pathogen produced abundant black, irregular sclerotia on
      surface of diseased plants and potato dextrose agar. The conidiophores and
      clusters of oval conidia resembled a grape-like cluster, the size of conidia was
      9.70-13.70 MUm [average of (11.32+/-0.82)MUm]*7.05-9.12 MUm [average of (8.24+/
      0.48)MUm], the microconidia produced on potato dextrose agar were spherical,and
      the size was (3.34+/-0.31) MUm,the pathogen was identified as Botrytis sp based
      on morphological characteristics. The DNA sequence analysis of the G3PDH, HSP60,
      RPB2 genes placed the pathogen in a single clade that outside defined species of
      Botrytis, so the pathogen could be identified as a new species of Botrytis. The
      pathogen requires 20  degrees C, pH 8, darkness or low light condition for the
      best growth.

PMID- 30111051
TI  - [Jasmonate signal pathway involved in phytoalexin biosynthesis in Sorbus
      aucuparia cell elicited by Hpa1].
AB  - The Harpin protein Hpa1 can induce defense responses in plant. This study aimed
      at investigating the role of jasmonate (JA) signal pathway in the process of
      biosynthesis of secondary metabolite in Sorbus aucuparia cell eliciting by Hpa1
      crude extract (Hpa1 CE). The results showed that Hpa1 crude extract (Hpa1 CE)
      could induce phytoalexin synthesis in S. aucuparia cell, most of which was
      noraucuparin and its glycosides. Meanwhile Hpa1 CE treatment resulted in methyl
      jasmonate (MeJA) production increased and noraucuparin was de novo synthesized in
      large quantities. Combination of Hpa1 CE and salicylhydroxamic acid (SHAM, JA
      signaling inhibitor) caused the decreased MeJA and noraucuparin in the S.
      aucuparia cell compared with that in Hpa1 CE group. Real-time PCR results
      indicated that Hpa1 CE treatment caused down-regulation of JAZ and up-regulation
      of mcy2 in transcription level. Therefore Hpa1 CE elicited defense mechanism and
      JA signaling pathway involved in phytoalexin biosynthesis in S. aucuparia cell.
      It presented information to elucidate the role of JA signal pathway in stress
      response in the perspective of secondary metabolism of plant.

PMID- 30111052
TI  - [Genetic diversity of 6 species in Polygonatum by SSR marker].
AB  - Polygonatum is a genus of the perennial herb family Liliaceae, with great
      potential in food, medicine and other field. In this study, genetic diversity and
      cluster structure analysis of 6 species in Polygonatum were investigated the
      molecular marker technique of simple sequence repeat (SSR). A total of 49 SSR
      makers were used to study genetic diversity and population structure within 60
      germplasm resources which obtained from 38 counties and cities in 14 provinces of
      China. A total of 211 alleles were identified and the number of alleles ranged
      from 2 to 10, with an average of 4.306 1 alleles per SSR. The range of
      polymorphism information content (PIC) varied from 0.731 8 to 0.031 7, with the
      average of 0.309 6. The cluster analysis classified 60 germplasm resources into
      four defined groups at the genetic distance value of 0.26, among which most
      species with relatives were clustered into the same group. Extraordinarily, there
      were 6 germplasm resources clustered into other species, indicating that the
      classification of inter-genus and geographical distribution was crossed in
      Polygonatum. The genetic diversity index of the 4 geographical populations from
      high to low was: Western region, Central China, Southern China, Eastern China.
      The population structure analysis, also indicating divided the entire collection
      into four groups, which was similar to the assignment pattern of cluster
      structure analysis. These results suggested that the Polygonatum germplasm
      resources used in this study is rich in relatively high genetic diversity with
      large variation range, relatively fuzzy boundaries of species. It appeared the
      phenomenon that there is a difference decreases between the alternate leaf system
      and the rotation leaf system. The genetic diversity in the western region was
      higher than that in other regions, and the western region may be the origin
      center of the genus Polygonatum.

PMID- 30111053
TI  - [Investigations on secondary metabolites of endophyte Diaporthe sp. hosted in
      Tylophora ovata].
AB  - One new compound (2S, 3S)-2,3-dihydroxybutyl 2-hydroxy-3,5,6-trimethylbenzoate
      (1) and six known compounds xylariphthalide A (2), convolvulol (3), cis-4-hydroxy
      6-deoxytalone (4), phomoxydienes B (5), 5,6-dihydroxy-2,3,6-trimethylcyclohex-2
      enone (6), trans-cyclo-(D-tryptophanyl-L-tyrosyl) (7) were isolated from
      Diaporthe sp., an endophytic fungus hosted in the leaves of the toxic Chinese
      folk medicine Tylophora ouata, using the combination methods of silica gel column
      chromatography, medium-pressure ODS column chromatography and RP-preparative
      HPLC. The structure of compound 1 was elucidated by NMR and MS data analyses. The
      absolute configurations were established according to the 1H-NMR data and exciton
      chirality method. Compound 1 inhibited the activation of human lung fibroblasts
      MRC-5 cells by 64.0% at 10 MUmol.L-1. The MTT assay showed that compounds 2 and 4
      displayed cytotoxic activity against human tumor cell lines BGC-823 cells with
      IC50 values of 1.5 and 8.6 MUmol.L-1, respectively.

PMID- 30111054
TI  - [Chemical constituents from roots of Viburnum setigerum].
AB  - This experiment was to study the constituents of the roots of Viburnum setigerum
      through various column chromatographic techniques. Thirteen compounds were
      obtained and their structures were identified using chemical and spectroscopic
      methods as (7alphaH, 8'alphaH)-4, 4', 8alpha-trihydroxy-3, 3', 9-trimethoxy-7, 9'
      epoxylignan (1), (7alphaH, 8'alphaH)-4, 4', 8alpha, 9-tetrahydroxy-3, 3'
      dimethoxy-7, 9'-epoxylignan (2), alashinol G (3), alashinol F (4), (-)
      secoisolariciresinol (5), (7R, 7'R, 8R, 8'S)-3, 3'-dimethoxy-7, 7'-epoxylignane 
      4, 4', 9, 9'-tetraol (6), (7alphaH, 8alphaH, 8'betaH)-4, 4', 7'alpha, 9
      tetrahydroxy-3, 3'-dimethoxy-7, 9'-epoxylignan (7), loganin (8), dihydroquercetin
      (9), protocatechuic acid (10), 4-hydroxy-3-methoxy-benzoic acid (11), adoxoside
      (12), and catechin (13). Compound 1 was a new compound. Compounds 3-7 and 11 were
      reported from the genus Viburnum for the first time. All compounds were separated
      from this plant for the first time.

PMID- 30111056
TI  - [Establishment of fingerprint of Astragali Radix polysaccharides based on endo
      1,4-beta-mannanase hydrolysis and identification of Astragali Radix of different
      germplasm resources].
AB  - The polysaccharides of different germplasm resources of Astragalus membranaceus
      var. mongholicus?(cultured Astragalus Radix (RA) and natural RA) and A.
      membranaceus (MJ) (cultured RA and natural RA) were studied by using the optimal
      enzymatic conditions of endo-1,4-beta-mannanase. Saccharide fingerprints were
      obtained for the identification and evaluation of the germplasm resources of RA
      by Fluorophore-assisted Carbohydrate Electrophoresis (FACE). The data were
      analyzed by principal component analysis to obtain the difference between RA of
      different germplasm resources. The results showed that trisaccharide,
      tetrasaccharide and pentasaccharide of endo-1,4-beta-mannanase hydrolyzate could
      be used as the differential fragments to distinguish MG (cultured RA and natural
      RA); the pentasaccharide and hexasaccharide can be used as differentially
      expressed carbohydrate fragments that distinguish MJ (cultured RA and natural
      RA); the trisaccharide and tetrasaccharide can be used as the differential
      fragments to distinguish the cultured MG and cultured MJ. Studies have shown that
      polysaccharide products degraded by endo-1,4-beta-mannanase can well distinguish
      RA species (MG and MJ), growth mode (cultured RA and natural RA). This study laid
      the foundation for the quality evaluation of Astragalus medicinal herbs and
      screening of active oligosaccharides.

PMID- 30111055
TI  - [Chemical constituents from water-soluble extract of dry roots of Paeonia
      lactiflora].
AB  - Nineteen compounds were isolated from the water-soluble extract of the dry roots
      of Paeonia lactiflora by using various chromatographic techniques. Their
      structures were identified by MS, NMR and other spectroscopic analysis as
      paeoniflorin(1), 4-O-ethylpaeoniflorin(2), 2'-O-benzoylpaeoniflorin(3),
      benzoylpaeoniflorin(4), 4"-hydroxy-benzoyloxypaeoniflorin(5), moudanpioside C(6),
      6'-O-benzoyl-4"-hydroxy-3"-methoxy-paeoniflorin(7), paeoniflorin B(8), 6-O
      benzoylalbiflorin(9), secoisolariciresinol (10), (+)-lyoniresinol(11),
      dihyrodehydrodiconiferyl alcohol(12), (7S,8S)-threo-7,9,9'-trihydroxy-3,3'
      dimethoxy-8-O-4'-neolignan(13), (+)-neo-olivil (14), [(3S)-5-methyl-2,3-dihydro-1
      benzofuran-3-yl]methanol(15), 5-hydroxy-3S-hydroxymethyl-6-methyl-2,3
      dihydrobenzofuran(16), (+)-(R)-2-hydroxy-1-(4-methoxyphenyl)-1-propan-1-one(17),
      (+)-(2R)-1-(4-hydroxy-3-methoxyphenyl)-2-propanol(18), (+)-(4S)-(2E)-4-hydroxy-2
      nonenoic acid(19). Compounds 15 and 18 are new natural products, while compounds
      10, 11, 13, 14, 17 and 19 are isolated from the genus Paeonia for the first time.

PMID- 30111058
TI  - [Therapeutic potential of n-butanol extract of Pulsatilla decoction in a murine
      model of ulcerative colitis induced by DSS combined with Candida albicans
      colonization].
AB  - To investigate the mechanism of n-butanol extract of Pulsatilla decoction (BAEB)
      against murine ulcerative colitis (UC) model induced by DSS combined with Candida
      albicans (CA) colonization, mice were randomly divided into normal control group,
      DSS group, DSS+CA group, BAEB high, medium and low dose group, and positive drug
      Mesalazine group. The general condition of mice was observed, fungal loads of
      murine intestinal contents were detected by plate method, colonic pathological
      change of mice was examined by HE staining. ASCA in serum and IL-6, IL-8, IL
      1beta, HBD-2, HBD-3 in colonic mucosa were detected by ELISA. The results showed
      that, compared with DSS group, the general condition and ASCA in serum had no
      obvious change for DSS+CA group, but the fungal loads in intestinal contents, the
      colonic pathological damage, and the levels of IL-6, IL-8, IL-1beta, HBD-2, HBD-3
      in colonic mucosa were greater than that of DSS group. High dose of BAEB group
      and Mesalazine group could improve the colonic pathology, decrease IL-6, IL-8, IL
      1beta, HBD-2, HBD-3 expression level. In conclusion, BAEB could effectively
      improve the UC symptoms in mice induced by DSS combined with CA colonization, and
      inhibit the inflammatory factors such as IL-6, imply that BAEB is of important
      value for the treatment of intestinal fungal-related colitis.

PMID- 30111057
TI  - [Protective effect of earthworm active ingredients against endoplasmic reticulum
      stress induced L-02 hepatocyte apoptosis].
AB  - This study focused on the protective effect of earthworm active ingredients
      (EWAs) on hepatocyte apoptosis induced by endoplasmic reticulum stress (ERS) in L
      02 cells. The L-02 cells were cultured in vitro. The cell viability was measured
      with CCK-8, the apoptosis of L-02 cells was detected by flow cytometry, and the
      relevant protein and mRNA expressions were detected by Western blot and qPCR.
      According to the findings, tunicamycin (TM) could obviously reduce the survival
      rate of L-02 cells in a time-dependent and dose-dependent manner. Compared with
      normal group, the apoptosis rate in model group was significantly increased
      (P<0.05 or P<0.01). The protein and mRNA expressions of ERS-related signal
      molecules, such as GRP78, PERK, eLF2alpha, ATF4, CHOP and Bax, were significantly
      up-regulated (P<0.05 or P<0.01), while Bcl-2 was significantly down-regulated
      (P<0.05 or P<0.01). After the administration with different concentrations of
      EWAs, compared with model group, EWAs could significantly increase the survival
      rate ofL-02 hepatocyte and decrease the cell apoptosis rates. It could also
      reduce the protein and mRNA expressions of ERS-related signal molecules, such as
      GRP78, PERK, eLF2alpha, ATF4, CHOP and Bax, in a dose-dependent manner (P<0.05 or
      P<0.01) and increased the protein and mRNA expressions of Bcl-2(P<0.05 or
      P<0.01). These results showed that EWAs had a significantly protective effect on
      hepatocyte apoptosis induced by ERS in L-02 cells. Its mechanism may be related
      to the down-regulation of mRNA and protein expressions of GRP78, PERK, ATF4,
      eLF2alpha, CHOP and Bax, and the up-regulation, the relief of ERS and the
      promotion of the proliferation of impaired L-02 cells.

PMID- 30111059
TI  - [Protective effect of Wuzi Yanzong recipe on testicular DNA oxidative damage in
      natural ageing rats].
AB  - To study the protective effects of Wuzi Yanzong recipe on DNA oxidative damage of
      testis germ cells in natural ageing rats based on Nrf2/HO-1 signaling pathway and
      base excision repair (BER). In the study, 16-month-old SPF grade male SD rats
      were randomly divided into three groups, namely ageing model group, and low and
      high-dose Wuzi Yanzong recipe groups (WZ, 1, 4 g.kg-1). In addition, 2-month-old
      SD rats were used as adult control group (10 rats in each group). The ageing
      model group and the adult control group were fed with normal diet for 4 months.
      WZ groups were given medicated feed for 4 months. After fasting for 12 hours, the
      rats were put to death. Then, the testes were immediately removed. The vitality
      of superoxide dismutase (SOD) and malondialdehyde (MDA) content in testis were
      detected by xanthine oxidase method and thiobarbituric acid (TBA) method. The
      levels of Nrf2 and 8-OHdG were detected by immunofluorescence. The protein
      expression levels of Nrf2, HO-1, NQO1, APE1, OGG1 and XRCC1 were detected by
      Western blot. Compared with the ageing model group, WZ significantly increased
      the SOD vitality and decreased MDA content of testis. In addition,
      immunofluorescence results showed that WZ significantly attenuated testicular DNA
      oxidative damage and improved antioxidant capacity. Such changes were accompanied
      by the down-regulation of DNA oxidative damage response protein 8-OHdG levels and
      the up-regulation of Nrf2 levels. Moreover, Western blot results showed that WZ
      significantly increased the protein expression levels of Nrf2, HO-1 and NQO1 of
      the testis germ cells, when compared with ageing model group. In parallel, the
      protein expression levels of APE1, OGG1 and XRCC1 were significantly decreased.
      In conclusion, WZ improves ageing-related DNA oxidative damage via Nrf2/HO-1 and
      BER pathways.

PMID- 30111060
TI  - [Hippocampus proteomics for effect of Er-xian decoction on ovariectomy induced
      learning and memory disabilities in rats].
AB  - To investigate the effect of Er-xian decoction on ovariectomy induced-learning
      and memory disability in rats based on the differences in hippocampus proteomic
      expression, the female rats were ovariectomized for perimenopausal status and
      then randomly divided into 3 groups, namely sham group, control group and Er-xian
      decoction group. The rats in sham group and control group were given normal
      saline by gavage everyday, the rats in Er-xian decoction group were given 12 g.kg
      1 of Er-xian decoction by gavage once a day. After treatment for 90 day, all of
      the animals were tested by Morris water maze, and all of the samples were
      collected for testing. The hippocampus proteins were detected by Nano-LC-LTQ
      Orbitrap system, and identified by Protein Discovery software. The intensity of
      differential proteins were quantitated by SIEVE software,and the biological
      functions of protein were analyzed by DIVAD database. The results showed that Er
      xian decoction could significantly improve the abilities of learning and memory.
      Compared with control group, 216 differential proteins with a consistent
      variation trend with the sham group were found in the Er-xian decoction group.
      And they mainly concentrated in calcium signaling pathway, Rab3A and Rab14 were
      key genes with the highest functional classification enrichment score in the gene
      group. Er-xian decoction could significantly improve the abilities of learning
      and memory in perimenopausal model rats. The invention effect of Er-xian
      decoction may be correlated with the calcium signaling pathway and Ras-related
      protein Rab-3A, and Ras-related protein Rab-14.

PMID- 30111061
TI  - [Methods to establishment of serum induced syndrome of liver-depression and
      spleen-deficiency cell model].
AB  - To explore the method of establishing a cell model of traditional Chinese
      medicine (TCM) syndromes, HepG2 cells were induced by human serum of liver
      depression and spleen-deficiency syndrome(LDSDS) to establish a cell model of
      LDSDS in this research. The concentration of cells, the content of human serum in
      culture medium and the growth characteristics of model-cell (cell growth curve,
      the survival rate and apparent morphology were investigated by MTT assay and
      microscopy. Evaluation of syndrome cell model: metabolomics was used to analyze
      the human serum of normal individuals and patients with LDSDS, and cell models
      induced by these serums, respectively. We obtained the difference metabolites
      from serums and cell models of LDSDS, respectively; then compared the biomarkers
      from two metabolomics and their metabolic pathways, to verify that the
      reliability and applicability of the model. Metabolomics data were collected by
      UPLC-Q-TOF-MS, and then all data were analyzed by multivariate statistical
      (PCA,OPLS-DA). The results showed that, model cells have the characteristics of
      normal growth, slow proliferation and stable morphological structure inducted by
      10% serum of LDSD in 24-72 h. There were the same 19 difference metabolites which
      from the human serum of normal individuals and patients with LDSDS, and cell
      models induced by these serums; including 9 metabolic pathways that play an
      important role in maintaining normal physiological activities of the human body,
      such as lipids, amino acids, nucleotides, and energy metabolism etc. It was shown
      that the established syndrome cell model can reflect the biological basis of
      LDSDS to some extent. This research provides a reference method for the
      establishment of TCM syndrome cell model.

PMID- 30111062
TI  - [Pharmacodynamics of Huanglian Jiedu decoction in Alzheimer's disease (AD) model
      rats and effect on improvement of inflammation microenvironment in brain].
AB  - To study the pharmacokinetics of active ingredients (alkaloids, iridoids and
      flavonoids) in Huanglian Jiedu decoction (HLJDD) in Alzheimer's disease (AD)
      model rats, and investigate its mechanism in treatment of AD. All of rats were
      divided into normal control group (n=6), shame operation group (n=6) and model
      group (n=12). Rats in shame operation group received daily subcutaneous injection
      of D-galactose (D-gal 50 mg.kg-1) for a total of 45 d to induce subacute aging
      model. Based on the operation of shame operation group, the rats in model group
      were given with an injection of Abeta25-35 (4.0 g.L-1)-ibotenic acid (2.0 g.L-1)
      into the nucleus basalis magnocellularis. Then rats in model group were divided
      into HLJDD one day administration group (n=6) and HLJDD one week group (n=6). The
      plasma concentration of alkaloids, iridoid and flavonoids was determined by
      liquid chromatography tandem mass spectrometry (LC-QQQ-MS) at different time
      points. The levels of seven inflammatory factors (MIP-2, IL-1beta, IL-2, IL-8, IL
      10, IL-13, TNF-alpha) in cerebrospinalfluid (CSF) were measured by Bio-Plex multi
      factor detection technology. Iridoids in AD model rats, with high
      bioavailability, were easily absorbed and eliminated. The plasma concentration of
      alkaloid was lower, and the AUC (area under the curve) was higher in HLJDD one
      week group than that in HLJDD one day group. The plasma concentration-time curves
      of flavonoids showed obvious bimodal phenomena. After the gastric administration
      of HLJDD, the inflammatory factors in CSF of AD rats demonstrated a callback
      trend, including IL-1beta/IL-10 (P<0.05) with significant difference. The
      pharmacokinetic behaviors of iridoids, alkaloids and flavonoids (41 compounds) in
      AD model rats were fundamentally elucidated, and HLJDD can improve the central
      inflammatory status of AD rats by regulating the levels of inflammatory factors.

PMID- 30111064
TI  - [Complex network analysis of law on Chinese herbal drugs intervention on
      radiation induced lung injury].
AB  - To mainly analyze the prescription rules of Chinese herbal drugs for radiation
      induced lung injury, optimize the prescriptions, and provide a reference for the
      clinical treatment of radiation induced lung injury. The major Chinese databases
      CNKI, CBM and Wanfang data were searched to obtain the literature on Chinese
      herbal drugs for radiation induced lung injury. BICOMS 2 software was used to
      extract and collect all Chinese herbal drugs information and generate the co
      occurrence matrix; NetDraw and Gcluto software were then used to make network map
      and visualization matrix for analysis. A total of 552 articles (19 types and 304
      Chinese herbal drugs) were included. Ophiopogon japonicus had the highest
      frequency (229 times), followed by Astragalus membranaceus(181 times),
      Glycyrrhiza uralensis (166 times), and Scutellaria baicalensis (150 times). After
      the classification of efficacy, deficiency-supplementing medicinal (69 kinds of
      Chinese herbs), heat-clearing medicine (51 kinds of Chinese herbs) and phlegm
      cough medicine (42 kinds of Chinese herbs) accounted for 53.29% of all the
      Chinese herbs, acting in the main position. After the prescription analysis for
      the top 25 herbal prescriptions, six main structures of common prescriptions were
      found for the treatment of radiation induced lung injury. There are many kinds of
      Chinese herbal drugs for the treatment of radiation induced lung injury in
      clinical application. In the future, researchers can mainly focus on Ophiopogon
      japonicus etc. as the main drugs, combine with other high-frequency Chinese
      herbal drugs found in this study, or directly refer to the main structures of
      commonly used prescriptions found in this analysis.

PMID- 30111066
TI  - [Discussion on application of principal component analysis in analysis of
      traditional Chinese medicines and natural drugs].
AB  - Principal component analysis is a widely used chemometric method. In this paper,
      the development history of principal component analysis was summarized, and then
      its basic principle was elaborated. Afterwards, its applications in the analysis
      of traditional Chinese medicines and natural drugs were classified and discussed
      with some representative examples. Finally, the prospect of its application was
      outlooked at the end of this paper.

PMID- 30111065
TI  - [Procalcitonin impact analysis, respiratory function and blood gas analysis on
      Xiaoqinglong decoction combined with non-invasive ventilation in treatment of
      AECOPD patients].
AB  - To observe the effect of Xiaoqinglong decoction combined with noninvasive
      ventilation on procalcitonin (PCT), blood gas analysis and respiratory functions
      in acute exacerbation of chronic obstructive pulmonary disease in the elderly
      (AECOPD), and investigate its correlation and clinical significance. Eighty-four
      elderly AECOPD patients with respiratory failure in our hospital from January
      2015 to October 2017, were randomly divided into control group and observation
      group, 42 cases in each group. The control group received western medicine
      combined with noninvasive ventilator therapy, and the patients in observation
      group additionally received Xiaoqinglong decoction on the basis of the treatment
      in control group. Both groups were treated for 2 weeks. The clinical effects of
      two groups were observed and their PCT, blood gas analysis outcomes [arterial
      oxygen partial pressure (PaO2), arterial partial pressure of carbon dioxide
      (PaCO2), respiratory function, forced vital capacity (FVC), forced expiratory
      volume in 1 second (FEV1), FEV1/FVC], TCM syndrome score and other indexes and
      adverse reactions were compared before and after treatment. The total efficiency
      was 95.24% (40/42) in observation group, higher than 76.19% (32/42) in control
      group, with statistically significant difference (P<0.05). There were no
      statistically significant differences in PCT, PaO2, PaCO2, FVC, FEV1/FVC, FEV1,
      and TCM syndrome scores between two groups before treatment. But after treatment,
      PCT and PaCO2 levels in the observation group were lower and PaO2, FVC, FEV1/FVC,
      FEV1 levels was higher than those in the control group (P<0.05); TCM syndrome
      scores were lower than those in the control group (P<0.05); both groups had no
      obvious adverse reactions. The results showed that Xiaoqinglong decoction
      combined with noninvasive ventilator could significantly reduce the procalcitonin
      level, effectively improve the respiratory function and blood gas analysis
      indexes, and significantly reduce the clinical symptoms in AECOPD patients, so it
      is worthy of promotion.

PMID- 30111063
TI  - [Effects of Renshenjian decoction on pancreatic metabonomic profiles in insulin
      resistance rats based on 1H-NMR metabonomics].
AB  - Pancreas metabonomic profiles of the type 2 diabetic rats' induced by
      streptozotocin(STZ) and high-sugar, high fat diet on the treatment of Renshenjian
      decoction(RSJD) after 8 weeks were investigated.In this study, 48 Rats were
      randomly divided into four groups: normal control (NC), Pathological model (PM),
      Renshenjian decoction(RSJD 3.76 g.kg-1) and glimepiride control (GC 0.04 mg.kg
      1). They are induced insulin resistance model of type 2 diabetes mellitus by
      streptozotocin(STZ) after 4 weeks' high-sugar, high fat diet except for NC. After
      sucessful modeling, they are given intragastric administration respectively with
      same amount of saline, RSJD and glimepiride in 4 weeks. At the end of the 8th
      week, the pancreatic tissue of rats in each group was collected, and the 1H-NMR
      spectrum was collected after being treated by certain method, and analyzed by
      principal component analysis (PCA). Compared with NC's rats, we found PM's a
      significant elevation in the level of leucine/isoleucine, valine, lactic acid,
      creatine but reduction in the level of inose and less obvious changes in the
      level of creatine, cholic acid, taurine in pancreatic extract. After having been
      recieved RSJD, reduction level in leucine/isoleucine, valine, alanine, creatine,
      choline, taurine are also found in pancreatic extract of RSJD's rats, together
      with the increase of creatinine and tryptophan levels. The results showed that
      RSJD could regulate the level of amino acids in pancreas of IR rats, promoting a
      recovery in the process of metabolism. It's helpful to simulate the metabolic
      changes of IR rats via 1H-NMR for a further understanding to study the mechanism
      how RSJD treat IR rats.

PMID- 30111067
TI  - [Scientific research on selection of medicinal herbs of Chloranthaceae based on
      materia medica theory].
AB  - The plants of Chloranthaceae are widely distributed and rich in resources in our
      country, records of ancient herbs indicaded that various species of plants of
      Chloranthaceae can be used for medicinal purposes, especially the Sarcandra
      glabra which with the least toxicity and possessed the function of clearing heat
      and cooling blood, activating blood to eliminate spots and removing wind and
      dredging collaterals. Based on the theory of herbage and by the method of
      consulting the past herbal literature, we summarized and analyzed the medicinal
      history, distribution characteristics of herbage geography, characteristics of
      herbage ecology, standard collection situation and the modern toxicology research
      of Chloranthaceae plants. Therefore we explained the scientificity for selection
      of medicinal herbs of Chloranthaceae plants, and provided a theoretical and
      scientific basis for further research of Chloranthaceae plants.

PMID- 30111068
TI  - Rapid appraisal of road-safety environmentaround educational institutions of
      Mangaluru city, South India
AB  - INTRODUCTION: Road traffic accidents (RTA) are the biggest killers according to
      the Global Status Report on Road Safety. OBJECTIVE: The objective of the present
      study was to assess the road safety in the vicinity of the educational
      institutions in the city of Mangaluru in South India. MATERIAL AND METHODS:
      Considering the proportion of educational institutions having road safety
      standards in place as 50%, absolute error as 5%, and z as 1.96 ( 95% confidence
      level), the required sample size was about 100 institutions. It was decided to
      sample approximately 100 each of government and private education institutions
      from a total of about 964 schools and colleges in the city limits of Mangaluru
      and survey them using a comprehensive checklist prepared based on some previous
      studies. RESULTS: Of the 200 schools observed for road safety features using a
      preformed checklist, 124 (62%) were located on the main road, 76 (38%) had an
      approach road from the main road to reach the school. Of these only 23 (11.5%) of
      institutions had road sign showing school/college, 14 (7%) had a signage showing
      children crossing, 37 (18.5) had a speed breaker for slowing of traffic and only
      2 (1%) had zebra crossing. Sixty four (32%) institutions had parking space and 12
      (6%) had sidewalk/pavement for safety. CONCLUSION: It was found that the road
      safety features and the safe environment around the schools were inadequate
      putting children, young adults and the employees of these institutions at risk.

PMID- 30111069
TI  - High prostate cancer mortality in Poland. A spatial, temporal and structural
      analysis
AB  - INTRODUCTION: This study investigates spatial distribution and future trends in
      prostate cancer mortality in Poland. Since detection of prostate cancer is based
      on patients' requests (not an invitation system), hypothesis of self-selection of
      patients was also verified MATERIAL AND METHODS: Age-period-cohort model was
      estimated to assess mortality trends. A spatial analysis was performed by
      Kulldorff's and Moran's tests. Structural equation model was fitted to identify
      factors influencing decision on participation in prostate cancer screening.
      Statistical analysis is based on data from the National Cancer Registry for 1980
      2014 and a 2014 questionnaire survey of 1,700 men aged 45+. RESULTS: The annual
      number of registered deaths due to prostate cancer is expected to increase from
      4,440 in 2014 to 6,550 in 2030. Prostate cancer mortality in Poland is to a large
      extent spatially uniform (global Moran's Ig=0.066) and was not found to be
      related to spatial patterns in oral contraceptive use in women which was recently
      hypothesised. Nevertheless, a Kulldorff's cluster can be identified over the
      Lubusz and Greater Poland areas for both the 1980-1984 and the 2010-2014 periods
      (p<0.001). The structural equation model showed that the early detection of
      prostate cancer is influenced mainly by physician's activeness and local
      availability of healthcare (p<0.050). The direct effect of socio-economic status
      on early detection of prostate cancer is insignificant. CONCLUSIONS: When
      considering prediction results, one should request more actions aimed at facing
      the upward trend of deaths, including making research funding in prostate cancer
      a priority, improving understanding of prostate cancer among males, and offering
      to patients individualised risk-adapted strategy modelled on the guidelines of
      the European Association of Urology. Currently, uptake of prostate cancer
      screening is largely affected by external factors.

PMID- 30111070
TI  - Stereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl) propanoate using the
      short-chain dehydrogenase/reductase ChKRED12.
AB  - Ethyl (S)-3-hydroxy-3-(2-thienyl)propanoate((S)-HEES)acts as a key chiral
      intermediate for the blockbuster antidepressant drug duloxetine, which can be
      achieved via the stereoselective bioreduction of ethyl 3-oxo-3-(2-thienyl)
      propanoate (KEES) that contains a 3-oxoacyl structure. The sequences of the short
      chain dehydrogenase/reductases from Chryseobacterium sp. CA49 were analyzed, and
      the putative3-oxoacyl-acyl-carrier-protein reductase, ChKRED12, was able to
      stereoselectively catalyze the NADPH-dependent reduction to produce (S)-HEES. The
      reductase activityof ChKRED12 towards other substrates with 3-oxoacyl structure
      were confirmed with excellent stereoselectivity (>99%ee) in most cases. When
      coupled with a cofactor recycling system using glucose dehydrogenase, the
      ChKRED12 was able to catalyze the complete conversion of 100 g/LKEES within 12 h,
      yielding the enantiopure product with >99% ee, showing a remarkable potential to
      produce(S)-HEES.

PMID- 30111071
TI  - Efficient Isolation and Characterization of a Cellulase Hyperproducing Mutant
      Strain of Trichoderma reesei.
AB  - A cellulase hyperproducing mutant strain, JNDY-13, was obtained using the ARTP
      mutation system and with Trichoderma reesei RUT-C30 as the parent strain. Whole
      genome sequencing of JNDY-13 confirmed that 105 of the 653 SNPs were point
      mutations, 336 mutations were deletions and 165 were insertions. Moreover, 99
      mutations were insertions and duplications. Among all the mutations, the one that
      occurred in the galactokinase gene might be related to the production of
      cellulases in T. reesei JNDY-13. Moreover, the up-regulation of cellulase and
      hemicellulase genes in JNDY-13 might contribute to higher cellulases production.
      Under optimal conditions, the highest cellulase activity by batch fermentation
      reached 4.35 U/ml, and the highest activity of fed-batch fermentation achieved
      was 5.40 U/ml.

PMID- 30111073
TI  - Flavobacterium amnigenum sp. nov. Isolated from a River.
AB  - A yellowish, flexirubin-pigment-producing strain I3-3T was isolated from river
      water in Iksan, the Republic of Korea. The strain was gram-negative, aerobic, non
      motile, showed catalase and oxidase activities, and could grow at a temperature
      range of 10-35 degrees C, pH 5.0-10 and 0-2.0% (w/v) of NaCl. The major fatty
      acids were iso-C15:0, iso-C17:0 3-OH and summed feature 3 (comprising
      C16:1omega7c and/or C16:1omega6c). The isolate contained
      phosphatidylethanolamine, one aminolipid, and two unidentified lipids as the
      major polar lipids. Menaquinone-6 (MK6) was the major respiratory quinone. The
      G+C content of the genomic DNA of strain I3-3T was 35.6%. Comparison of the 16S
      rRNA gene sequence with the sequences of the closely related type strains showed
      highest sequence similarity of 96.95% and 96.93% to Flavobacterium
      nitrogenifigens NXU-44T and Flavobacterium compostarboris 15C3T, respectively.
      Based on phenotypic and phylogenetic distinctiveness, strain I3-3T is considered
      as a member of novel species within the genus Flavobacterium, for which
      Flavobacterium amnigenum sp. nov. is proposed. The type strain is I3-3T (=KCTC
      52884T =NBRC 112871T).

PMID- 30111072
TI  - Dendrobium moniliforme Stem Extract Inhibits Lipoteichoic Acid-Induced
      Inflammatory Responses by Upregulation of Heme Oxygenase-1.
AB  - The stems of Dendrobium moniliforme have been used in traditional herbal medicine
      for the treatment of fever and lack of body fluid in Korea. In this study, we
      investigated anti-inflammatory effects of the aqueous extract of D. moniliforme
      stems (DM) in response to lipoteichoic acid (LTA), a major constituent of the
      cell wall of Gram-positive bacteria. DM inhibited LTA-induced expression of a pro
      inflammatory mediator inducible nitric oxide synthase (iNOS) in the murine
      macrophages. And DM induced expression of heme oxygenase-1 (HO-1) at the
      transcriptional level. Conversely, the knockdown of HO-1 expression by siRNA
      markedly reversed the inhibitory effects of DM on LTA-induced iNOS expression. We
      also demonstrated that nuclear translocation of Nrf2 was increased following
      treatment with DM. In addition, DM-mediated Nrf2 activation and HO-1 expression
      were suppressed by PI3K/Akt and p38 inhibitors; treatment with DM also resulted
      in phosphorylation of Akt and p38. These results suggest that DM inhibits the
      expression of iNOS in LTA-stimulated macrophages, and that these effects are
      mediated by the upregulation of HO-1 expression via PI3K/Akt/p38-Nrf2 signaling.

PMID- 30111074
TI  - Lactobacillus johnsonii CJLJ103 Attenuates Scopolamine-Induced Memory Impairment
      in Mice by Increasing BDNF Expression and Inhibiting NF-kappaB Activation.
AB  - In the present study, we examined whether Lactobacillus johnsonii CJLJ103 (LJ)
      could alleviate cholinergic memory impairment in mice. Oral administration of LJ
      alleviated scopolamine-induced memory impairment in passive avoidance and Y-maze
      tasks. Furthermore, LJ treatment increased scopolamine-suppressed BDNF expression
      and CREB phosphorylation in the hippocampi of the brain, as well as suppressed
      TNF-alpha expression and NF-kappaB activation. LJ also increased BDNF expression
      in corticosterone-stimulated SH-SY5Y cells and inhibited NF-kappaB activation in
      LPS-stimulated microglial BV2 cells. However, LJ did not inhibit
      acetylcholinesterase activity. These findings suggest that LJ, a member of human
      gut microbiota, may mitigate cholinergic memory impairment by increasing BDNF
      expression and inhibiting NF-kappaB activation.

PMID- 30111076
TI  - Epidemiological characteristics of patients with syphilis in Gdansk and Warsaw in
      2016
AB  - INTRODUCTION: Syphilis is a systemic disease with a complex natural history and a
      diversified clinical symptomology, taking various forms. It is characterized by a
      long-term course, often asymptomatic. The Global Estimates indicate that
      Treponema pallidum caused 5.6 million infections per year. AIM: Epidemiological
      characteristics of patients with syphilis in selected Polish urban agglomerations
      (Warsaw and Gdansk) in 2016. MATERIAL AND METHODS: Cases of syphilis reported by
      doctors to The Provincial Sanitary and Epidemiological Stations in Gdansk (50
      cases) and in Warsaw (520 cases) in 2016 were analysed. RESULTS: The average age
      of patients with syphilis was 35.2 years (Me=32 years). Men were more likely to
      suffer from syphilis - 493 cases (ie. 86.5%). The probable transmission route of
      the infection was indicated in 45% of cases and in 7.9% (45 people) it was
      undetermined sexual contact, in 11.6% (66 people) - heterosexual contact, and in
      24.4% (139 people) - homosexual contact. In 7 cases (ie 1.2%), the infection was
      transferred vertically. A statistically significant relationship was found
      between the route of infection and the sex of the infected person (p<0.01). The
      incidence of individual syphilis forms was significantly different between the
      examined cities (p<0.01). DISCUSSION: The group of people suffering from syphilis
      described in the study reflects the population of young people, especially men,
      living in urban agglomerations, characterized by mobility, considered the group
      most at risk of STI/ STD. The male-to-female rate among the respondents was 6.4:1
      and was similar to the overall rate in Europe in 2014, ie 6.2:1. Number of cases
      of early syphilis (39.5% of all reports in Warsaw and 80% in Gdansk) may suggest
      insufficient detection of infections in Gdansk and the need to intensify syphilis
      screening. In 2014, there were 69 cases of congenital syphilisn in the EU / EEA,
      of which every fourth newborn was born in Poland (n = 17). CONCLUSION: The latent
      syphilis form acquired mainly through heterosexual contacts has dominated among
      women suffering from syphilis. Amidst men syphilis was diagnosed mainly in the
      primary stage of infection and was most commonly acquired as a result of
      homosexual relationships. The epidemiological situation in Poland of syphilis,
      has been influenced by infections among MSM.

PMID- 30111075
TI  - Suppressive Effect of Fermented Angelica tenuissima Root Extract against
      Photoaging: Possible Involvement of Hemeoxygenase-1.
AB  - Angelica tenuissima root has historically been used as a traditional medicine in
      Korea. Previous studies have identified the anti-melanogenic effects of the
      extract of A. tenuissima root fermented by Aspergillus oryzae (FAT). This study
      investigated the protective effects of FAT against ultraviolet light B exposure
      (UVB; 30 mJ/cm2) in HaCaT (human keratinocyte) or Hs68 (human foreskin
      fibroblast) skin cells. FAT treatment was able to stimulate wound healing rate at
      the basal condition. FAT also favored the maintenance and/or improvement of
      extracellular matrix impairment caused by UVB irradiation through: 1)
      upregulation of procollagen Type-1 synthesis and secretion; 2) suppression of MMP
      1 and elastase expression. FAT was able to play a role in the attenuation of
      inflammatory responses caused by UVB irradiation via upregulation of photo
      protective hemeoxygease-1 and suppression of proinflammatory cyclooxygenase-2
      expression. After further verification of the anti-photoaging potential of FAT,
      it could be utilized as an effective ingredient in anti-aging and anti-wrinkle
      cosmetics.

PMID- 30111078
TI  - Evaluation on inflammatory states of peripheral veins connected with cannulation
      /
AB  - INTRODUCTION: Peripheral veins cannulation is one of the most frequently executed
      medical procedures. Primary blood infections which might be the result of
      peripheral veins cannulation are serious issue that medical care centers all over
      the world must consider. Medical personnel can choose the area of cannulation
      thanks to the availability of peripheral veins. Duration of cannulation longer
      than 72 - 96 hours can cause peripheral veins inflammation. AIM OF THE STUDY:
      Assay of observation sheets of peripheral cannulation. MATERIAL AND METHODS: The
      study included 14926 patients, who were hospitalized in 2016 in the Municipal
      Hospital in Zabrze. Observations of each cannulation were recorded in observation
      sheets for peripheral veins cannulation. Patients age median and duration of
      cannulation median were calculated basing on 782 observation sheets with
      registered inflammation of the area of cannulation. RESULTS: Right forearm was
      area where the most (19%) of vein inflammation occurred. First level of veins
      inflammation according to criteria of veins inflammation intensity evaluation was
      the most frequent (90,7%). Duration of venous cannulation median indicated that
      most of the catheters were removed on the second day. When veins inflammation was
      diagnosed, the most frequent action was to remove the catheter. During 12 hours
      697 observations of cannulation were proceeded. 548 observations of intravenous
      cannulation were proceeded once for 24 hours. CONCLUSIONS: Right forearm was area
      where the most of cannulations occurred. Frequent observation of the area of
      peripheral venous cannulation allows quick inflammation symptoms detection.

PMID- 30111077
TI  - Usefulness of SOFA score and artesunate - based treatment in severe malaria - a
      single center study
AB  - INTRODUCTION: This study was conducted to assess the usefulness of the guidelines
      of treatment recommended in Malaria diagnosis and treatment guideline published
      by University College London Hospitals-NHS Foundation Trust on 26th June 2013,
      usefulness of artesunate-based therapy and usefulness of SOFA (sepsis-related
      organ failure assessment) score in treatment of severe malaria. Severe malaria is
      usually caused by Plasmodium falciparum and most of the time fulfills the
      criteria of sepsis which are specified in the new definition of sepsis. The other
      malaria species are commonly considered to be the cause of mild course of
      malaria, however more and more cases of severe malaria are reported in the course
      of tertian fever malaria caused by Plasmodium vivax and in the disease caused by
      Plasmodium knowlesi. MATERIALS AND METHODS: Fourteen patients with malaria were
      hospitalized in the Department of Adults' Infectious Diseases and in the
      Intensive Care Unit of the Hospital for Infectious Diseases in Warsaw between
      December 2013 and April 2017. All patients were treated according to Malaria
      diagnosis and treatment guideline UCLH. RESULTS: Thirteen patients in our study
      fulfilled the criteria of severe malaria. All fourteen patients presented with a
      SOFA score >=2 points. Intravenous artesunate was administered to all patients in
      doses recommended in the UCLH guidelines. All patients presented with
      thrombocytopenia and elevated level of D-Dimers. The main factor influencing the
      dynamics of SOFA score was thrombocytopenia. All the patients fully recovered
      without any complications. CONCLUSIONS: The malaria treatment guidelines used in
      the Department for Infectious Diseases in Adults and in the Intensive Care Unit
      of the Hospital for Infectious Diseases in Warsaw in years 2013-2017 are
      effective. In assessing the severity of malaria SOFA score is useful especially
      as a warning of possibility of a severe course of the disease.

PMID- 30111079
TI  - Tuberculosis in Poland in 2016
AB  - AIM OF THE STUDY: To evaluate the main features of TB epidemiology in 2016 in
      Poland and to compare with the situation in the EU/EEA countries. METHODS:
      Analysis of case- based data on TB patients from National TB Register, data on
      anti-TB drug susceptibility testing results in cases notified in 2016, data from
      National Institute of Public Health- National Institute of Hygiene on cases of
      tuberculosis as AIDS-defining disease, data from Central Statistical Office on
      deaths from tuberculosis based on death certificates, data from ECDC report "
      European Centre for Disease Prevention and Control/WHO Regional Office for
      Europe. Tuberculosis surveillance and monitoring in Europe 2018- 2016 data.
      Stockholm: European Centre for Disease Prevention and Control, 2018". RESULTS: In
      2016, 6 444 TB cases were reported in Poland. The incidence rate was 16.8 cases
      per 100 000, with large variability between voivodships from 8.1 to 24.3 per 100
      000. The average decline of TB incidence was 3.0% per year during 2012- 2016. 5
      713 cases were new, never treated i.e. 14.9 per 100 000. 731 cases i.e. 1.9 per
      100 000 - 11.3% of all registered subjects were previously treated. In 2016, 6
      116 pulmonary tuberculosis cases occurred in Poland, equivalent to 15.9 per 100
      000. Pulmonary cases represented 94.9% of all TB cases. The number of pulmonary
      TB cases with bacteriological confirmation was 4475 i.e. 12,0 per 100 000. In
      2016, only 328 extrapulmonary TB cases were reported. Pediatric cases represented
      1.6% of the total TB cases in Poland; 103 children with TB were notified. The
      incidence of tuberculosis has been growing along with the age group from 1.8 per
      100 000 among children to 27.8 per 100 000 among patients aged 45 to 64 years. In
      the age group 65 years old and older the incidence was 26.0 per 100 000.The
      incidence among men i.e. 24.0 per 100 000 was >2 times higher than among women
      i.e. 10.0 per 100 000.The biggest difference in the TB incidence between the two
      sex groups occurred in persons aged 55 to 59 years - 51.9 vs. 11.5 and in
      subjects aged 60 to 64 years (45.9 vs. 11.7). The TB incidence in urban
      population was higher than in rural, respectively 17.3 per 100 000 and 15.9 per
      100 000.In 2016, the number of all culture positive TB cases was 4619. Culture
      confirmed cases represented 71.7% of all TB cases; culture-confirmed pulmonary TB
      - 73.2% of all pulmonary TB cases. In 2016, the number of smear-positive/culture
      positive pulmonary TB cases was 2612 (6.8 per 100 000) what represented 42.7% of
      all pulmonary TB cases. TB was initial AIDS indicative disease in 17 persons. In
      2016, 46 cases with MDR-TB (among them 10 foreigners) and 101 patients with
      resistance solely to isoniazid were reported in Poland, representing respectively
      1.1% and 2.4% of cases with known DST results (DSTs were done in 90.7% of all
      culture-confirmed TB cases). In 2016, there were 92 TB cases of foreign origin.In
      2015, there were 537 deaths due to tuberculosis in Poland, which is equivalent to
      1.4 deaths per 100 000 population; 520 people died from pulmonary and 17 from
      extrapulmonary tuberculosis. Mortality among males - 2.3 per 100 000 - was 3.8 x
      higher than among females - 0.6. The highest mortality rate was observed in
      subjects 65 years old and older - 3.3 per 100 000. There were no deaths from
      tuberculosis in children and adolescents. In 2015, TB mortality represented 0.14%
      of total mortality in Poland and 28.0% of mortality from infectious diseases.
      CONCLUSIONS: In 2016, the incidence of tuberculosis in Poland was slightly higher
      than in 2015 and higher than the average in the EU/EEA countries. The highest
      incidence rates were observed in older age groups. The incidence in males was
      more than 2 times higher than in females. The impact of migration on the
      characteristics of tuberculosis in Poland is low. In Poland, tuberculosis in
      children, tuberculosis in persons infected with HIV and MDR-TB is less common
      than the average in the EU/EEA countries.

PMID- 30111080
TI  - HIV and AIDS in Poland in 2016
AB  - AIM: The aim of the study was to assess the epidemiological situation of newly
      diagnosed HIV infections and AIDS cases in Poland in 2016 in comparison to the
      previous years. MATERIALS AND METHODS: Descriptive analysis of the
      epidemiological situation was based on reports of newly detected HIV cases and
      AIDS cases and the results of the annual survey of HIV testing conducted among
      the laboratories throughout the country. Data from the Department of Demographic
      and Labor Market Research of the Central Statistical Office on deaths due to HIV
      / AIDS were also used. RESULTS: In 2016 there were 1,313 HIV cases newly
      diagnosed in Poland (diagnosis rate: 3.42 per 100,000), including 44 among non
      Polish citizens. The number of newly detected HIV infections increased by nearly
      10% compared to the previous year and by almost 19% compared to the median in
      2010-2014. The total number of AIDS cases was 102 (incidence 0.27 per 100,000),
      and 102 people died of HIV disease (0.27 per 100,000). New HIV diagnoses were
      reported mainly in men (87.3%) and among people aged 20 to 39 years (71.2%).
      81.2% of cases in men with known transmission category concerned men who had
      sexual contact with men (MSM). CONCLUSIONS: The majority of new HIV cases are
      diagnosed in the MSM group. However, the assessment of the epidemiological
      situation is limited by the missing data on the likely route of transmission of
      newly detected HIV infections.

PMID- 30111081
TI  - Tetanus in Poland in 2016
AB  - THE PURPOSE of the STUDY: The purpose of the study was to provide data on tetanus
      incidence in 2016 in the basic categories of epidemiological surveillance.
      MATERIAL AND METHODS: The study is based on the individual forms of tetanus cases
      submitted to the NIZP-PZH Epidemiology Department and the data of the bulletin
      "Infectious Diseases and Poisoning in Poland in 2016. RESULTS: The number of
      tetanus cases in 2016 was 12, exactly as it was in the previous year 2015. Among
      the infected people there were six men and six women. Among the infected people
      two men and one women died. All the fatalities were in the age groups of 70 and
      older. SUMMARY AND CONCLUSIONS: The environmental nature of tetanus infections
      makes the immunity of individual exposed persons the basic preventive tool, which
      underlines the role of individual vaccinations.

PMID- 30111082
TI  - Hepatitis C in Poland in 2016
AB  - INTRODUCTION: In 2016, the World Health Organization implemented a Global
      Strategy to eliminate viral hepatitis. For Hepatitis C, the goals of this
      Strategy include increased harm reduction coverage, improved safety of medical
      procedures and an increase the percentage of people diagnosed and treated.
      OBJECTIVE: This article aims are evaluating the epidemiological situation of HCV
      infections in Poland in 2016 in reference to the data from previous years.
      MATERIAL AND METHODS: Analysis of epidemiological situation of hepatitis C in
      Poland in 2016 was carried out on case-based data collected through routine
      surveillance system. Data on hepatitis C mortality from the Demographic Surveys
      and Labour Market Department of the Central Statistical Office were also
      included. RESULTS: In 2016, a total of 4,261 cases were reported. Diagnosis rate
      was 11.09 per 100,000, on the similar level as in 2015 (1% decrease), but in
      comparison to the median for the years 2010-2014 it increased by 88%. The most
      common possible route of HCV infection were medical procedures accounting for
      69.8% of all cases and for 58.2% of acute hepatitis C virus infection cases. In
      2016, 224 deaths due to hepatitis C were registered. In 2016, a hepatitis C
      outbreak was reported in malopolskie voivodeship (11 patients of the Hemato
      oncolology Department, 129 people exposed). CONCLUSIONS: The increase of HCV
      diagnosis rate, which has been reported for last three years, is probably a
      consequence of improved the surveillance, including mandatory reporting of
      positive laboratory results, but also increased availability of HCV laboratory
      screening. Medical exposures are still an important route of transmission of HCV
      in Poland.

PMID- 30111083
TI  - Foodborne botulism in Poland in 2016
AB  - OBJECTIVES: The main aim of the study is to assess the epidemiological situation
      of foodborne botulism in Poland in 2016 compared to previous years. MATERIALS AND
      METHODS: In this assessment we reviewed national surveillance data on foodborne
      botulism cases published in the annual bulletin "Infectious diseases and
      poisonings in Poland in 2016" and in previous publications, as well as
      unpublished data retrieved from botulism case reports for 2016 sent from Sanitary
      Epidemiological Stations to the Department of Epidemiology NIPH-NIH. RESULTS: In
      2016, a total of 26 foodborne botulism cases (including 18 laboratory confirmed)
      were reported and the annual incidence rate (0.07 per 100,000 population) was
      slightly lower than both the previous year and the median incidence from 2010
      2014. The highest incidence in the country was noted in Lubelskie (0.33),
      Warminsko-mazurskie (0.28) and Zachodniopomorskie provinces (0.23). The incidence
      in rural areas (0.10 per 100,000 population) was twice as high as in urban areas
      (0.05); incidence among men was 8 times as high as among women; the highest
      incidence (0.36) was observed in men in the age group of 50-59 years. Most cases
      were associated with consumption of homemade canned fish or pork products and
      mixed or unknown types of canned meats. All patients were hospitalized. Three
      deaths related to the disease were reported. CONCLUSIONS: In 2016, the
      epidemiological situation of foodborne botulism in Poland has not changed
      significantly. This study suggests the need for training of health care
      professionals to improve diagnosis of botulism as well as continuous health
      education with respect to how to safely preserve, store and consume food at home.

PMID- 30111084
TI  - Legionellosis in Poland in 2016
AB  - OBJECTIVE: The aim of the study was to assess the epidemiological situation of
      legionellosis in Poland in 2016 in comparison to the preceding years. MATERIAL
      AND METHODS: The assessment was based on national surveillance data published in
      the annual bulletin: "Infectious diseases and poisonings in Poland in 2016" and
      its prior versions along with data from legionellosis case reports sent from
      Sanitary-Epidemiological Stations to the Department of Epidemiology of NIPH -
      NIH. RESULTS: In Poland, both two main forms of legionellosis - Legionnaires'
      disease and Pontiac fever are routinely reported to the surveillance system. In
      2016, a total of 27 cases of legionellosis were registered, including 25 cases of
      Legionnaires' disease and 2 cases of Pontiac fever; in 2016, a total of 27 cases
      of legionellosis have been reported, including 25 cases of Legionnaires' disease
      and 2 cases of Pontiac fever; the annual incidence rate 0.070 (per 100,000
      population) was comparable to previous year (0.060) but almost twice as high as
      the median (incidence) for 2010-2014. The infections were reported in 11
      provinces, including two, which in previous years usually did not register any
      cases; only two provinces (out of 16 in the country) have reported no cases in
      recent years. The incidence in men (0.080 per 100,000) was higher compared to
      women (0.055). All reported cases were sporadic and, except for one mild case of
      Legionnaires' disease, required hospitalization. The Sanitary Inspection reported
      two fatal cases - both women aged 59 and 69. Twenty cases were autochthonous
      including four cases linked with contaminated water systems in hospitals. Seven
      cases were associated with travel abroad (to Germany, Russia, Greece, Australia,
      USA and Thailand). SUMMARY AND CONCLUSIONS: Despite the increase in the number of
      cases in recent years as well as number of provinces, which detected cases, the
      annual incidence of legionellosis in Poland remains one of the lowest in the EU,
      which suggests that this infection is likely under-recognized and underdiagnosed
      in all provinces of the country.

PMID- 30111085
TI  - Infectious diseases in Poland in 2016
AB  - OBJECTIVE OF THE ARTICLE: This is for the year 2016 subsequent annual analysis of
      the situation of infectious and parasitic diseases in Poland as part of the
      Epidemiological Chronicle of the Epidemiological Review. Its purpose is to
      summarize the collective incidence of infectious diseases and to indicate
      potential threats to the health of populations from communicable diseases
      occurring in Poland. MATERIAL AND METHODS: The basic source of epidemiological
      information for this summary is a summary of data from reports of the State
      Sanitary Inspection, contained in the annual bulletins "Infectious diseases and
      poisoning in Poland in 2016" and "Protective Vaccination in Poland in 2016" (1,
      2). Supplementary sources are detailed assessments of the epidemiological
      situation of selected infectious diseases that make up the socalled
      Epidemiological Chronicle.Data on deaths were obtained from materials of the
      Department of Demographic and Labor Market Research of the Central Statistical
      Office regarding deaths from infectious and parasitic diseases registered in
      Poland in 2015 and in earlier years. RESULTS AND THEIR DISCUSSION: The most
      numerous group among infectious diseases subject to epidemiological surveillance
      are upper respiratory tract infections classified as "influenza and influenza -
      like disease".In 2016, the number this category cases was 4 316 823 (11 233.9 /
      100 000). In relation to incidence in 2015, it was an increase of 12.4%, and in
      relation to the median from 2010-2014 by 196.5%. In 2016, the incidence of
      intestinal infections of salmonellosis etiology increased compared to the
      previous year by 16.0%, and in relation to the median from 2010-2014 was higher
      19.1%. This is a deviation from the downward trend of these infections observed
      over last decades.A serious epidemiological problem is the high incidence of
      infection caused by Clostridium difficile. In 2016, 8 716 (22.7 / 100,000) of
      these cases were reported, which resulted in 540 deaths. In comparison with the
      previous year, it was a non-significant decline in incidence by 2.8%, but in
      comparison with the median from 2010-2014 it was an increase of 56.4%.In 2015,
      the high incidence of norovirus induced intestinal infection persisted. 3 706
      cases were reported (9.64/ 100 000), which is significantly higher than in 2015
      (by 2%), but in relation to the median from 2010-2014 it was an increase of
      136.6%. Among viral intestinal infections in children, rotavirus infections are
      still a particularly important problem.Despite the decrease in incidence in
      comparison with 2015 by 37.3%, the number of cases in 2016 was 21 258 (55.3 /
      100,000), which is a serious epidemiological problem. A high percentage of these
      incidents were infection related to the medical care. In the group of infections
      and intestinal intoxication, which cause diarrhea in children under 2 years, in
      2016 there was a decrease from the previous year of 11.7%, but in relation to the
      median from 2010-2014 it was an increase of 25.7%.In 2016 number of reported
      cases of pertussis was 6 828 (17.8 / 100 00), which represented a rise in
      incidence compared to the previous year by 37.9%, and compared to the median from
      2010-2014 by as much as 225%.The year 2016 was another year of decreasing the
      incidence of rubella. 1105 cases were reported (2.88 / 100 000), what in
      comparison with the previous year was a decrease of 44.9%, and in relation to the
      median of 2010-2014 by 81.2%.No congenital rubella was reported.For many years,
      Poland has been free of native measles. The measles cases are infections imported
      from abroad and secondary cases of people who have contacted them in the country.
      In 2016, cases were 133 (0.35 / 100 000).The number of invasive infections caused
      by Streptococcus pneumoniae in 2016 was 967. In comparison with 2015, it was a
      non-significant decrease of 1.2%.In 2016, there were 3 806 (9.9 / 100 000)
      reported cases of hepatitis B, which in relation to the median of 2010- 2014 is
      an increase of 141.0%. Number of newly diagnosed cases of hepatitis C was 4 261
      (11.1 / 100 000), which in relation to the median from 2010-2014 is an increase
      of 88.2%. This increase in incidence remains in a relationship. with the
      introduction in 2014 of a new, more sensitive case definition. 21 200 cases of
      Lyme disease were reported (55.2 / 100 000), which in comparison with the
      previous year, is an increase of 55.7%. As compared to the median of 2010-2014 it
      was increase by 132.1%.In 2016, number of cases of newly diagnosed HIV was 1318
      (3.43 / 100 000). And number of reported AIDS cases was 102. The increase in the
      incidence of HIV infection was not significant. The number of cases of AIDS fell
      by 20.3% as compared to the previous year.Registered cases of malaria refer to
      people who have been infected abroad in endemic countries. There were 38such
      cases in 2016.In 2015, no diphtheria, poliomyelitis, rabies and viral hemorrhagic
      fevers were found in Poland except for dengue, of which 41 cases of infections
      acquired in endemic areas were reported for epidemiological surveillance.The
      number of deaths from infectious and parasitic diseases in 2016 was 2 242 people.
      The share of deaths from these causes in the total number of deaths in Poland
      (388 009) was 0.58%.The highest number of deaths was caused by tuberculosis - 543
      and intestinal infections caused by Clostridium difficile - 540.

PMID- 30111086
TI  - Light-Activated Hybrid Nanocomposite Film for Water and Oxygen Sensing.
AB  - Oxygen and water vapor sensing properties are investigated in metal-oxide-hybrid
      polymer nanocomposite thin films generated by infiltration synthesis, which
      incorporates molecular ZnO into the matrix of SU-8 polymer, a common negative
      tone photoresist. The hybrid thin films display 20-fold higher gravimetric
      responses to oxygen and water vapor than those of control ZnO thin films in the
      dark. An additional 50-500% enhanced responses are detected under UV irradiation.
      The overall enhanced gravimetric response in the hybrid film is attributed to the
      ZnO molecules distributed in the polymer matrix, whereas the UV enhancement is
      explained by the light-induced, reversible generation of hydrophilic
      fluoroantimonic acid from triarylsulfonium hexafluoroantimonate photoacids, which
      leads to the increased surface potential and adsorption energies for oxygen and
      water. A gravimetric sensor based on a series of ZnO-infiltrated SU-8 films under
      UV excitation enables 96% accurate classification of water and oxygen environment
      with sub 10 mTorr detection limits. The results demonstrate UV-induced fully
      reversible surface hydrophilicity of ZnO/SU-8 hybrid nanocomposites.

PMID- 30111087
TI  - Impact of Titanium Dioxide on the Bioaccessibility of beta-Carotene in Emulsions
      with Different Particle Sizes.
AB  - Commercial, titanium dioxide (TiO2) ingredients used as color additives (E171) in
      foods and beverages contain an appreciable fraction of particles in the nanoscale
      range. At present, little information is available regarding the potential impact
      of food-grade TiO2 nanoparticles on the gastrointestinal fate of co-ingested
      bioactives, such as nutraceuticals. In this study, the impact of TiO2 on the
      bioaccessibility of beta-carotene solubilized in model food emulsions was
      investigated using a simulated gastrointestinal tract model. Raman spectroscopy
      showed that there was no charge transfer between beta-carotene and TiO2 but that
      some beta-carotene absorbed to the surface of TiO2 particles. The initial
      particle size of the food emulsion did not significantly affect beta-carotene
      bioaccessibility, probably because the same amount of free fatty acids (FFAs) was
      released by the end of digestion. The addition of TiO2 at levels typically found
      in foods also had no significant impact on beta-carotene bioaccessibility and FFA
      release, which suggested that this type of inorganic particle does not interfere
      with the gastrointestinal fate of these lipophilic bioactive agents. This
      information is important for ensuring the safety of inorganic nanoparticle
      utilization within the food industry.

PMID- 30111088
TI  - Design, Synthesis, and in Vitro and in Vivo Evaluation of High Affinity and
      Specificity Near-Infrared Fluorescent Bombesin Antagonists for Tumor Imaging.
AB  - The bombesin (BBN) antagonist binds with high affinity to the gastrin releasing
      peptide receptor (GRPr), a receptor overexpressed on many human cancers. We
      present an investigation employing BBN antagonist for highly specific near
      infrared fluorescence (NIRF) imaging of GRPr-positive tumors. Nine NIRF-dye
      labeled BBN antagonists with differing linkers and dyes were synthesized and
      characterized to screen for the optimal agent. Three novel agents, AF750-G-pip
      Sta-BBN (1), AF750-GSG-Sta-BBN (2), and AF750-6Ahx-Sta-BBN (3), exhibited an
      excellent binding-specificity and affinity to human PC-3 prostate cancer cells in
      vitro, and a remarkable in vivo tumor-selectivity and NIRF imaging sensitivity in
      PC-3 tumor-bearing mice. Compound 1 showed the fastest, and 3, the slowest,
      pharmacokinetics on the tumor sites. Despite of high tumor uptake, 2 had a low
      pancreas uptake distinct from 1 and 3 at 0.44 nmol dose. This difference was
      attributed to the inherent linker properties such as the hydrophilicity,
      polarity, and charge.

PMID- 30111089
TI  - Fabrication and Characterization of Starch Nanohydrogels via Reverse
      Emulsification and Internal Gelation.
AB  - Biopolymer-based nanohydrogels have great potential for various applications,
      including in food, nutraceutical, and pharmaceutical industries. Herein, starch
      nanohydrogels were prepared for the first time via reverse emulsification coupled
      with internal gelation. The effects of starch type (normal corn, potato, and pea
      starches), amylose content, and gelation time on the structural, morphological,
      and physicochemical properties of starch nanohydrogels were investigated. The
      diameter of starch nanohydrogel particles was around 100 nm after 12 h of
      retrogradation time. The relative crystallinity and thermal properties of starch
      nanohydrogels increased gradually with an increasing amylose content and gelation
      time. The swelling behavior of starch nanohydrogels was dependent upon the
      amylose content, and the swelling ratios were between 2.0 and 14.0, with the pea
      starch nanogels exhibiting the lowest values and the potato starch nanogels
      exhibiting the highest values.

PMID- 30111090
TI  - Altered Coordination of Individual Catalytic Steps in Different and Evolved
      Inteins Reveals Kinetic Plasticity of the Protein Splicing Pathway.
AB  - Protein splicing performed by inteins provides powerful opportunities to
      manipulate protein structure and function, however, detailed mechanistic
      knowledge of the multistep pathway to help engineering optimized inteins remains
      scarce. A typical intein has to coordinate three steps to maximize the product
      yield of ligated exteins. We have revealed a new type of coordination in the Ssp
      DnaB intein, in which the initial N- S acyl shift appears rate-limiting and acts
      as an up-regulation switch to dramatically accelerate the last step of
      succinimide formation, which is thus coupled to the first step. The structure
      activity relationship at the N-terminal scissile bond was studied with atomic
      precision using a semisynthetic split intein. We show that the removal of the
      extein acyl group from the alpha-amino moiety of the intein's first residue is
      strictly required and sufficient for the up-regulation switch. Even an acetyl
      group as the smallest possible extein moiety completely blocked the switch.
      Furthermore, we investigated the M86 intein, a mutant with faster splicing
      kinetics previously obtained by laboratory evolution of the Ssp DnaB intein, and
      the individual impact of its eight mutations. The succinimide formation was
      decoupled from the first step in the M86 intein, but the acquired H143R mutation
      acts as a brake to prevent premature C-terminal cleavage and thereby maximizes
      splicing yields. Together, these results revealed a high degree of plasticity in
      the kinetic coordination of the splicing pathway. Furthermore, our study led to
      the rational design of improved M86 mutants with the highest yielding trans
      splicing and fastest trans-cleavage activities.

PMID- 30111091
TI  - Preparation and Characterization of Insulin-Loaded Zein/Carboxymethylated Short
      Chain Amylose Complex Nanoparticles.
AB  - In this work, we use antisolvent precipitation to prepare zein/carboxymethylated
      short-chain amylose (CSA) complex nanoparticles for insulin encapsulation,
      showing that insulin-loaded zein/CSA complex nanoparticles are homogeneous,
      generally exhibiting sizes of <200 nm with a narrow distribution (polydispersity
      index < 0.100), spherical shape, and strong negative charge (-40 mV). Fourier
      transform infrared spectroscopy analysis reveals that the formation of the above
      nanoparticles is mainly driven by hydrophobic, hydrogen-bonding, and
      electrostatic interactions between CSA, insulin, and zein. In comparison to zein
      nanoparticles, zein/CSA complex nanoparticles feature much higher insulin
      encapsulation efficiency (45.8 versus 90.5%, respectively) and are essentially
      nontoxic to Caco-2 cells. Thus, this work provides new insights into the design
      of drug delivery systems and is expected to inspire their further development.

PMID- 30111092
TI  - Dual Superlyophobic Aliphatic Polyketone Membranes for Highly Efficient
      Emulsified Oil-Water Separation: Performance and Mechanism.
AB  - Efficient treatment of difficult emulsified oil-water wastes is a global
      challenge. Membranes exhibiting unusual dual superlyophobicity (combined
      underwater superoleophobicity and underoil superhydrophobicity) are intriguing to
      realize high-efficiency separation of both oil-in-water and water-in-oil
      emulsions. For the first time, a robust polymeric membrane demonstrating dual
      superlyophobicity to common apolar oils was facilely fabricated via a simple one
      step phase separation process using an aliphatic polyketone (PK) polymer, thanks
      to a conjunction of intermediate hydrophilicity and re-entrant fibril-like
      texture upon the prepared PK membrane. Further chemical modification to improve
      surface hydrophilicity slightly can enable dual superlyophobicity to both apolar
      and polar oils. It is found that a nonwetting composite state of oil against
      water or water against oil was obtainable on the membrane surfaces only when the
      probe liquids possess an equilibrium contact angle (thetaow or thetawo) larger
      than the critical re-entrant angle of the textured surfaces (73 degrees ), which
      can explain the existences of dual superlyophobicity and also the nonwetting to
      fully wetting transitions. A simple design chart was developed to map out the
      operational windows of material hydrophilicity and re-entrant geometry, that is,
      a possible zone, to help in the rational design of similar interfacial systems
      from various materials. Switchable filtrations of oil-in-water and water-in-oil
      nanoemulsions were achieved readily with both high flux and high rejection. The
      simplicity and scalability of the membrane preparation process and the well
      elucidated underlying mechanisms illuminate the great application potential of
      the PK-based superwetting membranes.

PMID- 30111093
TI  - In Situ Chemical Analysis of the Gas-Aerosol Particle Interface.
AB  - The gas-aerosol particle interface is believed to contribute to the growth of
      secondary organic aerosols in the atmosphere. Despite its importance, the
      chemical composition of the interface has not been probed directly because of a
      lack of suitable interface-specific analytical techniques. The preliminary result
      in our early work has demonstrated direct observations of molecules at the gas
      aerosol particle interface with the development of second harmonic scattering
      (SHS). However, the SHS technique is far away from being an analytical tool of
      chemical compositions at the gas-aerosol particle interface. In this work, we
      continued to develop the interface-specific SHS for in situ chemical analysis of
      molecules at the gas-aerosol particle interface. As an example, we demonstrated
      coherent SHS signal of a new SHS probe, crystal violet (CV), from interfaces of
      aerosol particles. The development of the SHS technique includes: (1)
      Optimization for a more efficient femtosecond laser system in the generation of
      SHS from aerosol particles. A near 5 MHz repetition rate of a femtosecond laser
      was found to be optimal for the generation of SHS; (2) exploration of a more
      effective detector for SHS of aerosol particles. We found that both a CCD
      detector and a single-photon counter produce similar signal-to-noise ratios of
      the interfacial SHS signals from aerosol particles. The CCD detector is a more
      effective option for the detection of SHS and could greatly reduce sampling time
      of the interfacial responses; (3) combination of the optimal laser system with
      the CCD detector, which has greatly improved the detection sensitivity of
      interfacial molecules by more than 2 orders of magnitude and could potentially
      detect interfacial SHS from a single aerosol particle. These experimental results
      not only provided a thorough analysis of the SHS technique but also built a solid
      foundation for further development of a new vibrational sum frequency scattering
      (SFS) technique for chemical structures at the gas-aerosol particle interface.

PMID- 30111094
TI  - Adsorption and Incorporation of Arsenic to Biogenic Lepidocrocite Formed in the
      Presence of Ferrous Iron during Denitrification by Paracoccus denitrificans.
AB  - We demonstrate adsorption and partial incorporation of arsenic, in its soluble
      form, either as arsenite or arsenate into lepidocrocite (gamma-FeOOH), which was
      formed through nitrite-driven Fe(II) oxidation by Paracoccus denitrificans under
      nitrate-reducing conditions. Fe and As K-edge XANES and radial distribution
      functions of Fourier-transformed EXAFS spectra showed that portions of As were
      found to be incorporated in the biogenic lepidocrocite, in addition to higher
      portions of adsorbed As. We suggest that denitrifying bacteria such as Paracoccus
      denitrificans, studied here, could facilitate decrease of aqueous arsenic As(III)
      and/or As(V) through indirect Fe(II) oxidation to solid phase iron minerals, here
      as lepidocrocite, by the denitrification product nitrite in the presence of
      nitrate, ferrous iron, and arsenic, under certain environmental conditions where
      these materials could be found, such as in As-contaminated paddy soils and
      wetlands.

PMID- 30111095
TI  - Inhibition of the Exoglucanase Cel7A by a Douglas-Fir-Condensed Tannin.
AB  - Douglas-fir forestry residues are a potential feedstock for saccharification
      based biofuels, and condensed tannins are expected to make up ~3% of the dry mass
      of this feedstock. Condensed tannins are well-known for their ability to interact
      with proteins and can bind and inhibit cellulase enzymes used in
      saccharification. In this study, we use molecular docking and classical molecular
      dynamics simulations to investigate how a characterized condensed tannin from
      Douglas-fir bark binds to the exoglucanase Cel7A from Trichoderma reesei. Through
      looking at the "occupancy" and "residency" of specific amino acid residue-tannin
      interactions, we find that the binding sites are characterized by many
      simultaneous tannin-enzyme interactions with the strongest occurring on the
      catalytic module as opposed to the carbohydrate-binding module. The simulations
      indicate that tannin inhibition can result from binding at or near the catalytic
      tunnel's entrance and exit. The analyzed tannin further prefers to bind to loops
      around the catalytic region and has affinity for aromatic and charged amino acid
      residues. These insights provide direction for the rational design of tannin
      resistant cellulases.

PMID- 30111096
TI  - Sub-Ocean: Subsea Dissolved Methane Measurements Using an Embedded Laser
      Spectrometer Technology.
AB  - We present a novel instrument, the Sub-Ocean probe, allowing in situ and
      continuous measurements of dissolved methane in seawater. It relies on an optical
      feedback cavity enhanced absorption technique designed for trace gas measurements
      and coupled to a patent-pending sample extraction method. The considerable
      advantage of the instrument compared with existing ones lies in its fast response
      time of the order of 30 s, that makes this probe ideal for fast and continuous 3D
      mapping of dissolved methane in water. It could work up to 40 MPa of external
      pressure, and it provides a large dynamic range, from subnmol of CH4 per liter of
      seawater to mmol L-1. In this work, we present laboratory calibration of the
      instrument, intercomparison with standard method and field results on methane
      detection. The good agreement with the headspace equilibration technique followed
      by gas-chromatography analysis supports the utility and accuracy of the
      instrument. A continuous 620-m depth vertical profile in the Mediterranean Sea
      was obtained within only 10 min, and it indicates background dissolved CH4 values
      between 1 and 2 nmol L-1 below the pycnocline, similar to previous observations
      conducted in different ocean settings. It also reveals a methane maximum at
      around 6 m of depth, that may reflect local production from bacterial
      transformation of dissolved organic matter.

PMID- 30111097
TI  - Cell-Specific Chemical Delivery Using a Selective Nitroreductase-Nitroaryl Pair.
AB  - The utility of small molecules to probe or perturb biological systems is limited
      by the lack of cell-specificity. "Masking" the activity of small molecules using
      a general chemical modification and "unmasking" it only within target cells
      overcomes this limitation. To this end, we have developed a selective enzyme
      substrate pair consisting of engineered variants of E. coli nitroreductase (NTR)
      and a 2-nitro- N-methylimidazolyl (NM) masking group. To discover and optimize
      this NTR-NM system, we synthesized a series of fluorogenic substrates containing
      different nitroaromatic masking groups, confirmed their stability in cells, and
      identified the best substrate for NTR. We then engineered the enzyme for improved
      activity in mammalian cells, ultimately yielding an enzyme variant (enhanced NTR,
      or eNTR) that possesses up to 100-fold increased activity over wild-type NTR.
      These improved NTR enzymes combined with the optimal NM masking group enable
      rapid, selective unmasking of dyes, indicators, and drugs to genetically defined
      populations of cells.

PMID- 30111098
TI  - Stability of the Metabolite Signature Resulting from the OsSULTR3;3 Mutation in
      Low Phytic Acid Rice ( Oryza sativa L.) Seeds upon Cross-breeding.
AB  - The low phytic acid ( lpa) rice ( Oryza sativa L.) mutant Os-lpa-MH86-1,
      resulting from the mutation of the putative sulfate transporter gene OsSULTR3;3,
      was crossed with a commercial rice cultivar. The obtained progenies of
      generations F4 to F7 were subjected to a nontargeted metabolite profiling
      approach allowing the analyses of a broad spectrum of lipophilic and hydrophilic
      low-molecular-weight constituents. The metabolite profiles of the homozygous lpa
      progenies were characterized not only by a decreased concentration of phytic acid
      but also by increased contents of constituents from various classes, such as
      sugars, sugar alcohols, amino acids, phytosterols, and biogenic amines.
      Statistical assessments of the data via multivariate and univariate approaches
      demonstrated that this mutation-induced metabolite signature was nearly
      unaffected by the cross-breeding step and consistently expressed over several
      generations. The data demonstrate that even for complex metabolic changes
      resulting from a mutation, cross-breeding can be employed as a tool to generate
      progeny rice seeds stably exhibiting the mutation induced traits.

PMID- 30111099
TI  - Salt-Induced Colloidal Destabilization, Separation, Drying, and Redispersion in
      Aqueous Phase of Cationic and Anionic Nanochitins.
AB  - This study is aimed at facilitating the use of ocean biomass for the isolation
      and use of derived nanostructures. Specifically, cationic and anionic nanochitins
      were produced from never-dried crab shells that underwent partial deacetylation
      (PD-NCh) or TEMPO-oxidization (TO-NCh). The effects of different electrolyte
      types (NaCl, CH3COONa, Na2CO3, CaCl2, AlCl3, and NH4Cl) were investigated with
      regards to fractionation (via colloidal destabilization and precipitation),
      drying, and ultimate redispersion of the nanochitins. Sodium carbonate was most
      effective in the case of PD-NCh processing, whereas no significant effect of salt
      type was noted for TO-NCh. The results are rationalized in terms of the
      dispersion stability that resulted from specific counterion adsorption and
      nanoparticle association as well as electrostatic-charge development at a given
      solution pH. These effects were used to limit hydrogen bonding and nonspecific
      interactions upon drying of the nanochitins. The weak interactions between
      nanochitin and monovalent Na+ and NH4+ explain the experimental observations.
      Aqueous dispersions reconstituted from dried PD-NCh and TO-NCh were colloidally
      stable and yielded highly viscous, gel-like nanochitin dispersions at mass
      concentrations as low as 1.5 and 3.0%, respectively. Our findings are expected to
      greatly facilitate green processing of nanochitin, an emerging type of biobased
      nanomaterial.

PMID- 30111100
TI  - Operando Spectroscopic Identification of Active Sites in NiFe Prussian Blue
      Analogues as Electrocatalysts: Activation of Oxygen Atoms for Oxygen Evolution
      Reaction.
AB  - Developing highly efficient oxygen evolution reaction (OER) catalysts and
      understanding their activity are pivotal for electrochemical conversion
      technologies. Here, we report NiFe Prussian blue analogue (PBA) as a promising
      electrocatalyst for OER in alkaline conditions. This material has an impressively
      low overpotential of 258 mV that reaches a current density of 10 mA cm-2. Post
      mortem characterization showed that the as-prepared catalyst is entirely
      transformed into amorphous nickel hydroxide after the electrochemical treatment,
      and Ni(OH)2 acts as the active species. Operando X-ray spectroscopic studies
      further found that this in situ generated Ni(OH)2 displays an unique feature that
      allows deprotonation under applied potential creating NiOOH2- x that contains
      Ni4+ ions. The deprotonation reaction is reversible and potential-dependent,
      i.e., the amount of Ni4+ increases with increasing applied potential. Theoretical
      calculations were used to show that the role of Ni4+ is to trigger oxidized
      oxygen ions as electrophilic centers with the subsequent activation of anion
      redox reactions for OER.

PMID- 30111101
TI  - Direct Observation of Acyl Nitroso Compounds in Aqueous Solution and the Kinetics
      of Their Reactions with Amines, Thiols, and Hydroxamic Acids.
AB  - Acyl nitroso compounds or nitrosocarhonyls (RC(O)N?O) are reactive short-lived
      electrophiles, and their hydrolysis and reactions with nucleophiles produce HNO.
      Previously, direct detection of acyl nitroso species in nonaqueous media has been
      provided by time-resolved infrared spectroscopy demonstrating that its half-life
      is about 1 ms. In the present study hydroxamic acids (RC(O)NHOH) are oxidized
      electrochemically in buffered aqueous solutions (pH 5.9-10.2) yielding transient
      species characterized by their maximal absorption at 314-330 nm. These transient
      species decompose via a first-order reaction yielding mainly HNO and the
      respective carboxylic acid and therefore are ascribed to RC(O)N?O. The
      sufficiently long half-life of RC(O)N?O in aqueous solution allows for the first
      time the study of the kinetics of its reactions with various nucleophiles
      demonstrating that the nucleophilic reactivity follows the order thiolate >
      hydroxamate > amine. Metal chelates of CH3C(O)NHOH catalyze the hydrolysis of
      CH3C(O)N?O at the efficacy order of CuII > ZnII > NiII > CoII where only CuII
      catalyzes the hydrolysis also in the absence of the hydroxamate. Finally,
      oxidation of hydroxamic acids generates HNO, and the rate of this process is
      determined by the half-life of the respective acyl nitroso compound.

PMID- 30111102
TI  - Physico-Chemical Changes of Composite Whey Protein Hydrogels in Simulated Gastric
      Fluid Conditions.
AB  - Polysaccharide blended whey protein isolate (WPI) hydrogels were developed for
      the delivery of black carrot ( Daucus carota) concentrate as bioactive agent in
      simulated gastric fluid (SGF). Pectin (PC), gum tragacanth (GT), and xanthan gum
      (XG) were blended as additional polymers to modulate the release characteristics
      of the WPI hydrogels. Experiments showed that sole whey protein (C), XG, and GT
      blended hydrogels possessed restricted release profiles 67%, 61%, and 67%,
      respectively, whereas PC samples attained higher release rates (83%) ( p < 0.05).
      Interactions between polymers and aqueous medium were analyzed by nuclear
      magnetic resonance relaxometry. C (82 ms) and GT (84 ms) hydrogels attained
      higher T2 values than PC (74 ms) and XG (73 ms) samples in SGF. Hardness of only
      XG hydrogels increased from 1.9 to 4.1 N after gastric treatment. Physicochemical
      changes within hydrogels during release were also investigated, and hydrogels
      were proved to be appropriate for desired delivery purposes.

PMID- 30111103
TI  - Uncovering the Hidden Excited State toward Fluorescence of an Intracellular pH
      Indicator.
AB  - Intracellular pH (pHi) imaging is of paramount importance for life sciences. In
      this work, we implement the ultrafast electronic and stimulated Raman
      spectroscopies to unravel the fluorescence mechanism of an excitation-ratiometric
      pHi indicator in basic aqueous solution. After photoexcitation of the pHi
      indicator HPTS, a hidden charge-transfer (CT) state following the locally excited
      (LE) state is uncovered as an essential step prior to fluorescence and this LE ->
      CT transition is gated by ultrafast solvation dynamics. A 835 cm-1 intermolecular
      vibrational mode is identified to potentially facilitate the CT-state formation
      on the 700 fs time scale. Dynamic correlation with the other excited-state Raman
      marker bands suggests that the transition between transient electronic states is
      aided by solvation events mostly in the molecular plane of HPTS. These vivid
      structural dynamics insights can enable the rational design of more efficient and
      bright pHi indicators in an H-bonding environment with controllable properties.

PMID- 30111105
TI  - Vitamin E Has Reduced Affinity for a Polyunsaturated Phospholipid: An Umbrella
      Sampling Molecular Dynamics Simulations Study.
AB  - Vitamin E is an essential micronutrient. The primary function of this lipid
      soluble antioxidant is to protect membrane phospholipids from oxidation. Whether
      vitamin E preferentially interacts with polyunsaturated phospholipids to optimize
      protection of the lipid species most vulnerable to oxidative attack has been an
      unanswered question for a long time. In this work, we compared the binding of
      alpha-tocopherol (alphatoc), the form of vitamin E retained by the human body, in
      bilayers composed of polyunsaturated 1-stearoyl-2
      docosahexaenoylphosphatidylcholine (SDPC, 18:0-22:6PC) and, as a control,
      monounsaturated 1-stearoyl-2-oleoylphosphatidylcholine (SOPC, 18:0-18:1PC) by
      umbrella sampling molecular dynamics simulations. From the potential of mean
      force as a function depth within the bilayer, we find that the binding energy of
      alphatoc is less in SDPC (Delta Gbind = 16.7 +/- 0.3 kcal/mol) than that in SOPC
      (Delta Gbind = 18.3 +/- 0.4 kcal/mol). The lower value in SDPC is ascribed to the
      high disorder of polyunsaturated fatty acids that produces a less tightly packed
      arrangement. Deformation of the bilayer is observed during desorption, indicating
      that phosphatidylcholine (PC)-PC and alphatoc-PC interactions contribute to the
      binding energy. Our results do not support the proposal that vitamin E interacts
      more favorably with polyunsaturated phospholipids.

PMID- 30111104
TI  - Antifungal Activity of Nanochitin Whisker against Crown Rot Diseases of Wheat.
AB  - Nanochitin whisker (NC) is a rodlike particle with a cationic nature and high
      biological activities. Crown rot, caused by soil-borne fungal pathogens including
      Fusarium pseudograminearum( Fp) and Fusarium graminearum( Fg), is one of the most
      damaging diseases in wheat. To explore the antifungal activity of NC against
      wheat diseases, the effects of nanochitin whisker suspension (NCs) on fungal
      growth and conidial production of Fp and Fg were studied in vitro. NCs and its
      mixture with chemical fungicide as a seeds coating agent for crown rot disease
      control were also investigated using Fp as a model microorganism in a pot test.
      The results showed that NCs had significant inhibitory effects on mycelial growth
      and conidial production of Fp and Fg at concentrations of 30 and 300 ppm in the
      growth medium. Particularly, 300 ppm of NCs was capable of reducing conidial
      formation 89.25% and 82.28% for Fp and Fg, respectively. When seeds were treated
      with a mixture of NCs and tebuconazole, the disease control efficiencies
      increased to 79.30% and 90.02% for NCs at concentrations of 10 and 30 ppm,
      respectively. Greener and shorter seedlings were also observed in the pot
      experiment. This indicates that NCs have strong antifungal activity against the
      soil-borne pathogens of wheat and reduce use of chemical fungicide in wheat
      plantation.

PMID- 30111106
TI  - Identification of Active Sites in Oxidation Reaction from Real-Time Probing of
      Adsorbate Motion over Pd Nanoparticles.
AB  - Obtaining insight into the type of surface sites involved in a reaction is
      essential to understand catalytic mechanisms at the atomic level and a key for
      understanding selectivity in surface-catalyzed reactions. Here we use ultrafast
      broad-band vibrational spectroscopy to follow in real-time diffusion of CO
      molecules over a palladium nanoparticle surface toward an active site. Site-to
      site hopping is triggered by laser excitation of electrons and followed in real
      time from subpicosecond changes in the vibrational spectra. CO photoexcitation
      occurs in 400 fs and hopping from NP facets to edges follows within ~1 ps.
      Kinetic modeling allows to quantify the contribution of different facet sites to
      the catalytic reaction. These results provide useful insights for understanding
      the mechanism of chemical reactions catalyzed by metal NPs.

PMID- 30111107
TI  - Fulgides as Light-Driven Molecular Rotary Motors: Computational Design of a
      Prototype Compound.
AB  - A new family of light-driven molecular rotary motors utilizing the fulgide motif
      is proposed and its prototype molecule is studied by quantum chemical
      calculations and nonadiabatic molecular dynamics simulations. The new motor
      performs pure unidirectional axial rotation of the rotor blade with high quantum
      efficiency (phi ~ 0.55-0.68) and ultrafast dynamics (? t? S1 ~ 200-300 fs) of its
      successive photoisomerization steps. The photocyclization reaction typical of
      fulgide compounds is blocked by the design of the new motor and never occurred in
      the molecular dynamics simulations. The new motors can be synthesized from easily
      available precursors. In view of its remarkable photoisomerization ability, the
      new motor represents a prospective class of compounds for the use in nanosized
      molecular devices.

PMID- 30111108
TI  - Grazing-Angle Neutron Diffraction Study of the Water Distribution in Membrane
      Hemifusion: From the Lamellar to Rhombohedral Phase.
AB  - The water distribution between lipid bilayers is important in understanding the
      role of the hydration force at different steps of the membrane fusion pathway. In
      this study, we used grazing-angle neutron diffraction to map out the water
      distribution in lipid bilayers transiting from a lamellar structure to the
      hemifusion "stalk" structure in a rhombohedral phase. Under osmotic pressure
      exerted by different levels of relative humidity, the lipid membrane sample was
      maintained in equilibrium at different lattices suitable for neutron diffraction.
      The D2O used to hydrate the lipid membrane sample stood out from the lipid in the
      reconstructed structure because of its much higher coherent neutron scattering
      length density. The density map indicates that water dissociated from the
      headgroup in the lamellar phase. In the rhombohedral phase, water was
      significantly reduced and was squeezed into pockets around the stalk. This study
      complements earlier structural studies by grazing-angle X-ray diffraction, which
      is sensitive to only the parts of the structure with high electron density (such
      as phosphors). The experiment also demonstrated that the recently developed time
      of-flight small-angle neutron scattering beamline at the Spallation Neutron
      Source is suitable for grazing-angle neutron diffraction to provide the
      structures of large unit cells on the order of a few nanometers, such as
      biomembrane structures.

PMID- 30111109
TI  - Optical Phonon Behaviors of Photocharged Nanocrystals: Effects of Free Charge
      Carriers.
AB  - For semiconductor nanocrystals (NCs), the precise knowledge of phonons in the
      presence of free carriers is important for understanding their electronic and
      photonic properties in device applications. With Raman spectroscopy, this study
      investigates the effects of free charge carriers on optical phonon behaviors of
      NCs. The adoption of the photocharging method allows us to introduce free charge
      carriers into NCs without inducing other side effects. In the photocharged ZnO
      NCs, lower longitudinal optical (LO) phonon frequencies and weaker LO overtones
      relative to the fundamentals were found, which was explained by the screening and
      band-filling effects caused by the induced free carriers. The free carrier
      effects on optical phonon behaviors of NCs, usually neglected in previous
      studies, should be taken into consideration when discussing the electronic and
      photonic properties of NC-based devices.

PMID- 30111110
TI  - Water Retention of Calcium-Containing Pectin Studied by Quartz Crystal
      Microbalance and Infrared Spectroscopy with a Humidity Control System.
AB  - To examine differences of water-retention mechanisms between pectins with and
      without Ca2+, quartz crystal microbalance (QCM) and infrared microspectroscopy
      combined with a humidity-control system were used to analyze differences in
      amounts and species of adsorbed water to pectins without and with Ca2+. QCM
      analysis shows that water contents are ~2-3 times larger for the pectin film with
      Ca2+ than that without Ca2+. The difference IR spectra suggest that long, medium,
      and short H-bond water molecules (free, medium, and bound water) are adsorbed to
      the pectin film without Ca2+. IR peak shifts of C?O of COOH and C-OH suggest that
      these water molecules are hydrogen-bonded to C?O and C-OH groups. In addition to
      these water molecules, bulk water is adsorbed. IR OH band areas fitted by four
      Gaussian components show that bulk water is mainly adsorbed to the pectin film
      with Ca2+, possibly among skeletal chains of pectin bridged by Ca2+.

PMID- 30111111
TI  - Learning from Correlations Based on Local Structure: Rare-Earth Nickelates
      Revisited.
AB  - Statistical analysis of local atomic distortions in crystalline materials is a
      powerful tool for understanding coupled electronic and structural phase
      transitions in transition metal compounds. The analyses of such complex
      materials, however, often require significant domain knowledge to recognize
      limitations in the available data, whether it be experimentally reported crystal
      structures, property measurements, or computed quantities, and to understand when
      additional experiments or simulations may be necessary. Here we show how
      additional descriptive statistics and computational experiments can help
      researchers explicitly recognize these limitations and fill in missing gaps by
      constructing amplitude ( a) and normalized-amplitude ( n) distortion-mode
      property correlation-coefficient heat maps, aCCHMs and nCCHMs, respectively. We
      demonstrate this utility within the rare-earth nickelate perovskites RNiO3 (R =
      rare earth ? La), which exhibit antiferromagnetic and metal-insulator transitions
      with crystallographic symmetry breaking, and analyze the CCHMs obtained from
      experimental and first-principles derived symmetry modes. In contrast with the
      crystallographic trends gleaned from the reported experimental structures, the
      equilibrium structures obtained from density functional theory indicate that the
      Jahn-Teller distortion mode plays a negligible role in affecting the Neel
      temperature. We explain this discrepancy and discuss how different researchers
      might draw disparate conclusions from the same evidence, in particular from
      aCCHMs and nCCHMs. Last, we propose a general method for utilizing CCHMs for
      screening large databases of structures.

PMID- 30111113
TI  - Geometrical and Structural Dynamics of Imatinib within Biorelevant Colloids.
AB  - Solubilization of lipophilic drugs is essential for efficient uptake. We detail
      the solubilization of imatinib in simulated gastrointestinal fluids containing
      taurocholate (TC) and lecithin (L) and reflecting fasted versus fed states using
      NMR spectroscopy, X-ray diffractometry, transmission electron microscopy, and
      dynamic light scattering analysis. Imatinib concentration impacted colloidal
      geometries and molecular dynamics in a fasted state. At drug substance
      concentrations up to 250 MUM, imatinib was mainly engulfed within the core of
      >110 nm in diameter vesicles. At higher drug concentrations, the colloids
      collapsed to <40 nm, and imatinib migrated into the shell of the micelles, mainly
      being associated with the lipophilic face of TC but not with L. Simulating the
      fed state resulted in the formation of small micelles independent of the drug
      concentration. Furthermore, a hydrogel was formed, effectively keeping the drug
      substance in an amorphous state even when stressed by drying. In conclusion, this
      study detailed the fascinating dynamics of colloidal structures and molecular
      assembly as a function of imatinib concentration in biorelevant conditions. This
      approach may provide a blueprint for the rational development of future
      pharmaceutical formulations, taking the molecular interactions with bile
      salts/phospholipids into account.

PMID- 30111114
TI  - Driving Forces for Accumulation of Cellulose Nanofibrils at the Oil/Water
      Interface.
AB  - Understanding the adsorption and organization of nanocelluloses at oil/water
      interfaces is crucial to develop a promising route to fabricate functional
      materials from the bottom-up. Here, we prepare acetylated cellulose nanofibrils
      (CNFs) with 2 degrees of substitution and investigate their assembly behavior at
      the oil/water interface. We study the adsorption process by tracking the dynamic
      interfacial tension using pendant drop tensiometry and further characterize the
      viscoelasticity of the CNF interfacial films as a function of ionic strength. The
      results show that the adsorption of the CNFs at the interface is dominated by
      energy barriers associated with electrostatic repulsion. With the addition of
      NaCl, the fibrils are rapidly accumulated at the oil/water interface and jammed
      into a solidlike film. The overall accumulation of the fibrils is related to the
      competition between van der Waals attractive forces and electrostatic repulsive
      forces according to the Derjaguin-Landau-Verwey-Overbeek theory. By screening on
      the fibril-fibril and fibril-interface electrostatic repulsive forces, the salt
      addition facilitates the formation of packed fibril clusters and the development
      of the clusters into a solidlike film. Moreover, the salt addition is assumed to
      trigger an abrupt density fluctuation in the vicinity of the interface (the
      formation of locally dense clusters and voids), leading to an increase in
      brittleness of the film.

PMID- 30111112
TI  - Gingival Exudatome Dynamics Implicate Inhibition of the Alternative Complement
      Pathway in the Protective Action of the C3 Inhibitor Cp40 in Nonhuman Primate
      Periodontitis.
AB  - Periodontitis is a prevalent chronic inflammatory disease associated with
      dysbiosis. Although complement inhibition has been successfully used to treat
      periodontitis in animal models, studies globally analyzing inflamed tissue
      proteins to glean insight into possible mechanisms of action are missing. Using
      quantitative shotgun proteomics, we aimed to investigate differences in
      composition of inflammatory gingival tissue exudate ("gingival crevicular fluid";
      GCF), before and after local administration of an inhibitor of the central
      complement component, C3, in nonhuman primates. The C3 inhibitor, Cp40 (also
      known as AMY-101) was administered locally in the maxillary gingival tissue of
      cynomolgus monkeys with established periodontitis, either once a week (1*
      treatment; n = 5 animals) or three times per week (3*-treatment; n = 10 animals),
      for 6 weeks followed by another 6 weeks of observation in the absence of
      treatment. 45 GCF samples were processed for FASP digestion and liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Data were processed
      using the ProgenesisQI software. The statistical significance of differences
      between the groups was determined by RM-ANOVA, and a protein expression change
      was considered as a true regulation at >2-fold and p < 0.05. The human
      orthologues were subjected to Gene Ontology analyses using PANTHER. Data are
      available via ProteomeXchange with identifier PXD009502. 573 proteins with >2
      peptides were longitudinally quantified. Both 3* and 1* administration of Cp40
      resulted in significant down-regulation of dozens of proteins during the 6-week
      course of treatment as compared to baseline. Following drug withdrawal at 6
      weeks, more than 50% of the down-regulated proteins showed increased levels at
      week 12. The top scored pathway was "complement activation, alternative pathway",
      and several proteins involved in this pathway were down-regulated at 6 weeks. We
      mapped the proteomic fingerprint changes in local tissue exudate of cynomolgus
      monkey periodontitis in response to C3 inhibition and identified the alternative
      pathway of complement activation and leukocyte degranulation as main targets,
      which are thus likely to play significant roles in periodontal disease
      pathogenesis. Label-free quantitative proteomics strategies utilizing GCF are
      powerful tools for the identification of treatment targets and providing insights
      into disease mechanisms.

PMID- 30111115
TI  - Locally Induced Spin States on Graphene by Chemical Attachment of Boron Atoms.
AB  - Pristine graphene is known to be nonmagnetic due to its pi-conjugated electron
      system. However, we find that localized magnetic moments can be generated by
      chemically attaching boron atoms to the graphene sheets. Such spin-polarized
      states are evidenced by the spin-split of the density of states (DOS) peaks near
      the Fermi level in scanning tunneling spectroscopy (STS). In the vicinity of
      several coadsorbed boron atoms, the Coulomb repulsion between multiple spins
      leads to antiferromagnetic coupling for the induced spin states in the graphene
      lattice, manifesting itself as an increment of spin-down state at specific
      regions. Experimental observations and interpretations are rationalized by
      extensive density functional theory (DFT) simulations.

PMID- 30111116
TI  - Superconductor-Insulator Transitions in Exfoliated Bi2Sr2CaCu2O8+delta Flakes.
AB  - We realize superconductor-insulator transitions (SIT) in mechanically exfoliated
      Bi2Sr2CaCu2O8+delta (BSCCO) flakes and address simultaneously their transport
      properties as well as the evolution of density of states. Back-gating via the
      solid ion conductor (SIC) engenders a SIT in BSCCO due to the modulation of
      carrier density by intercalated lithium ions. Scaling analysis indicates that the
      SIT follows the theoretical description of a two-dimensional quantum phase
      transition (2D-QPT). We further carry out tunneling spectroscopy in
      graphite(G)/BSCCO heterojunctions. We observe V-shaped gaps in the critical
      regime of the SIT. The density of states in BSCCO gets symmetrically suppressed
      by further going into the insulating regime. Our technique of combining solid
      state gating with tunneling spectroscopy can be easily applied to the study of
      other two-dimensional materials.

PMID- 30111117
TI  - Strong Adhesion of Graphene Oxide Coating on Polymer Separation Membranes.
AB  - Graphene oxide (GO) has been demonstrated as the most promising candidate for
      surface modification of polymer separation membranes for durable filtration
      applications. However, the adhesion between GO coating and polymer substrate, as
      the most essential issue for reliable applications, has been little explored.
      Herein, we developed a facile high-pressure assisted deposition method to
      physically anchor GO sheets on microfiltration (MF) and reverse osmosis (RO)
      membranes, and established a tape test procedure for assessing the adhesion of GO
      coating to polymer substrates based on the ASTM D3359. Through regulating the GO
      sources and coating process, we demonstrated that the adhesion depends
      sensitively on the GO flake size and deposition pressure, whereas the adhesion
      level dramatically improved from 0B to 5B, with decrease in the lateral size of
      GO and increase in the coating deposition pressure. The strong GO coatings showed
      evidently higher water flux than that of weak counterparts. The underlying
      mechanism was further analyzed and verified. Nanosize of GO and high deposition
      pressure favor the formation of the conformal morphologies of GO coatings on both
      MF and RO membranes, which allow strong interfacial van der Waals interaction
      because of the large contact areas and result in the strong GO coatings on
      membranes. These results potentially open up a versatile pathway to develop the
      strong graphene-based coatings on separation membranes.

PMID- 30111118
TI  - Edge State Engineering of Graphene Nanoribbons.
AB  - Zigzag edges of graphene nanoribbons, which are predicted to host spin-polarized
      electronic states, hold great promise for future spintronic device applications.
      The ability to precisely engineer the zigzag edge state is of crucial importance
      for realizing its full potential functionalities in nanotechnology. By combining
      scanning tunneling microscopy and atomic force microscopy, we demonstrate the
      zigzag edge states have energy splitting upon fusing manganese the phthalocyanine
      molecule with the short armchair graphene nanoribbon termini. Moreover, the edge
      state splitting can be reversibly switched by adsorption and desorption of a
      hydrogen atom on the magnetic core of manganese phthalocyanine. These
      observations can be explained by tuning the zigzag edge local doping through the
      charge transfer process, which provides a new route to functionalize graphene
      based molecular devices.

PMID- 30111119
TI  - Spotlights: Volume 9, Issue 16.

PMID- 30111120
TI  - Extending the hierarchical quantum master equation approach to low temperatures
      and realistic band structures.
AB  - The hierarchical quantum master equation (HQME) approach is an accurate method to
      describe quantum transport in interacting nanosystems. It generalizes
      perturbative master equation approaches by including higher-order contributions
      as well as non-Markovian memory and allows for the systematic convergence to the
      numerically exact result. As the HQME method relies on a decomposition of the
      bath correlation function in terms of exponentials, however, its application to
      systems at low temperatures coupled to baths with complexer band structures has
      been a challenge. In this publication, we outline an extension of the HQME
      approach, which uses re-summation over poles and can be applied to calculate
      transient currents at a numerical cost that is independent of temperature and
      band structure of the baths. We demonstrate the performance of the extended HQME
      approach for noninteracting tight-binding model systems of increasing complexity
      as well as for the spinless Anderson-Holstein model.

PMID- 30111121
TI  - First-order properties from internally contracted multireference coupled-cluster
      theory with particular focus on hyperfine coupling tensors.
AB  - Internally contracted multireference coupled-cluster (icMRCC) theory is extended
      to the computation of first-order properties (expectation values). We use the
      previously defined Lagrange formulation of the energy functional to derive the
      required equations for the Lagrange multipliers and arrive at an expression for
      first-order properties according to the generalized Hellmann-Feynman theorem,
      analogous to single-reference coupled-cluster theory. The present formulation
      does not include orbital relaxation, but in line with previous experience in
      coupled-cluster theory, the single-excitation cluster operator can recover a
      significant portion of orbital relaxation. Further aspects of the theory that
      arise from the internal contraction approach are discussed. Using automated
      derivation techniques, we have implemented a pilot code for icMRCCSD and
      icMRCCSDT for testing the method numerically. We find good agreement with full
      configuration interaction for several properties of boron monohydride and dipole
      moment curves of hydrogen fluoride and chromium hydride. A particular focus is
      given to spin-dependent properties: The hyperfine coupling tensors of Sigma and
      Pi radicals have been computed and compared to experiment and previous
      computations. We discuss the problem of describing spin polarization with
      properly spin-adapted wavefunctions, which requires either including pseudo
      triple excitations or employing sufficiently flexible reference functions.

PMID- 30111122
TI  - Efficient configurational-bias Monte-Carlo simulations of chain molecules with
      "swarms" of trial configurations.
AB  - The pruned-enriched Rosenbluth method (PERM) is a popular and powerful Monte
      Carlo technique for sampling flexible chain polymers of substantial length. In
      its original form, however, the method cannot be applied in Markov-chain Monte
      Carlo schemes, which has rendered PERM unsuited for systems that consist of many
      chains. The current work builds on the configurational-bias Monte-Carlo (CBMC)
      method. The growth of a large set of trial configurations in each move is
      governed by simultaneous pruning and enrichment events, which tend to replace
      configurations with a low statistical weight by clones of stronger
      configurations. In simulations of dense brushes of flexible chains, a gain in
      efficiency of at least three orders of magnitude is observed with respect to CBMC
      and one order of magnitude with respect to recoil-growth approaches. Moreover,
      meaningful statistics can be collected from all trial configurations through the
      so-called "waste-recycling" Monte Carlo scheme.

PMID- 30111123
TI  - Growth of films with anisotropic particles: Simulations and rate equations.
AB  - By means of computer simulations and kinetic rate equations, we study the
      formation of a film of rod-like particles which are deposited on a substrate. The
      rod-rod interactions are hard with a short-range attraction of variable strength
      and width, and the rod-substrate interactions favor lying rods with a variable
      strength. For a rod aspect ratio of 5 and deposition of up to an equivalent of
      one monolayer of standing rods, we demonstrate a rich variety of growth modes
      upon variation of the three interaction parameters. We formulate rate equations
      for the time evolution of densities of islands composed of standing, lying, and
      mixed rods. Input parameters such as diffusion constants, island capture numbers,
      and rod reorientation free energies are extracted from simulations, while rod
      reorientation attempt frequencies remain as free parameters. Numerical solutions
      of the rate equations in a simple truncation show rough qualitative agreement
      with the simulations for the early stage of film growth but an extension to later
      stages requires to go significantly beyond this simple truncation.

PMID- 30111124
TI  - Why do higher VDEs of superhalogen not ensure improved stabilities of the noble
      gas hydrides promoted by them? A high-level ab initio case study.
AB  - A series of 20 composite structures, consisting of superhalogen and noble gas
      (Ng) hydrides, was explored via high-level coupled-cluster single, double and
      perturbative triple excitations calculations in this work. The existence of these
      composites, as local minima on the potential energy surface, arises from the
      charge transfer from the Ng hydride part to the superhalogen moiety. Clearly,
      this transfer could lead to stabilizing the interaction of the ionic type between
      the two components. The driving force of the charge transfer should be the high
      vertical electron detachment energy (VDE) of the superhalogen part leading to its
      enough capability of extracting the electron from the Ng hydride moiety. However,
      except triggering the ionic attractive interaction, there is nomonotonic
      correlation between the VDE value and the thermodynamic stability of the whole
      composite. This counter-intuitive result actually originates from the fact that,
      irrespective of various superhalogens, only two of their F ligands interact with
      the Ng atoms directly. Thus, although leading to higher VDE values, the increase
      in the number of electronegative ligands of the superhalogen moiety does not
      affect the stabilizing interaction of the composites here directly. In other
      words, with the necessary charge transfer generated, further increase of the VDE
      does not ensure the improvement of the thermodynamic stabilities of the whole
      composite. Moreover, in the transition state of the exothermic dissociation
      channel, more F atoms will give rise to higher probability of additional
      attractions between the F and H atoms which should lower the energy barrier. That
      is to say, increasing VDE, i.e., having more F atoms in many cases, will probably
      reduce the kinetic stability. Knowing the inevitable existence of the exothermic
      channel, kinetic stability is crucial to the ultimate goal of experimental
      observation of these Ng hydrides. Thus, in some cases, only the superhalogen
      itself may not provide enough information for the correct prediction on the
      properties of the whole composites. The understanding of the superhalogen-based
      composites will provide valuable information on the functional properties as well
      as the application potential of superhalogen clusters. Thus, the corresponding
      researches should focus on not only the superhalogen itself but also other
      related aspects, especially the details of the interaction between different
      parts.

PMID- 30111125
TI  - Impact of offset energies on the yield of interfacial charge separation in
      molecular photocells.
AB  - We display that the process of charge carriers' separation at molecular
      photocells is a complex phenomenon that is controlled by the cumulative action of
      Coulomb interaction for electron-hole pairs and LUMO-LUMO offset energies. By
      applying quantum scattering theory and the Lippmann-Schwinger equation, we
      provide a comprehensive framework of the device operation in which the operating
      molecular photocell is described by a wave function. We find that depending on
      the magnitude of offset energies, the electron-hole interaction can normally
      decrease or abnormally increase the charge separation yield. To rationalize the
      results, we benefit from the spectral information provided in the model. Our
      analysis helps to optimize molecular photocells operation.

PMID- 30111126
TI  - Efficient scheme for calculating work of adhesion between a liquid and polymer
      grafted substrate.
AB  - We propose a method for calculating the work of adhesion between a liquid and
      solid surface by using molecular simulations. Two ideas are introduced for
      efficient calculation when the proposed method is applied at the interface
      between a liquid and a polymer-grafted substrate. First, the liquid molecules are
      separated from the solid surface based on its shape by placing spherically
      symmetric potentials around the atoms selected from the substrate and the
      polymers grafted onto it. Second, to avoid deterioration of accuracy during
      numerical integration of the work, the parameters that appear in the potential
      are updated so that variations in the gradient of the work are suppressed. This
      method is applied to the interface between water and a gold substrate modified by
      poly(ethylene oxide) (PEO), and it is found that the work of adhesion is greater
      at intermediate PEO densities.

PMID- 30111127
TI  - Well converged quantum rate constants for the H2 + OH -> H2O + H reaction via
      transition state wave packet.
AB  - Transition state wave packet calculations have been carried out to compute
      cumulative reaction probabilities for the H2 + OH reaction on the NN1 potential
      energy surface, as given in the work of Chen et al., from which well converged
      thermal rate constants for the reaction up to a temperature of 1000 K were
      obtained. It was found that both the centrifugal sudden approximation and the "J
      K-shifting" approximation slightly underestimated the thermal rate constants,
      while the ring-polymer molecular dynamics overestimated the rates in the low
      temperature region. After considering the correction of the barrier height by
      spin-orbit coupling effect and the more accurate level of theory, the calculated
      rate constants were in good consistency with experimental measurements in the
      entire temperature region for this benchmark reaction.

PMID- 30111128
TI  - Density functional study of dendrimer molecules in solvents of varying quality.
AB  - Modified inhomogeneous statistical associating fluid theory (iSAFT) density
      functional theory is extended to dendrimer molecules in solvents of varying
      quality. The detailed structures of isolated dendrimers in implicit solvent are
      calculated and have a semi-quantitative agreement with simulation results
      available in the literature. The dendrimers form dense-core structures under all
      conditions, while their radius of gyration follows different scaling laws.
      Factors that affect the quality of the solvent are systematically studied in the
      explicit solvent case. It is found that the solvent size, density, chemical
      affinity and temperature all play a role in determining a solvent to be good or
      poor. New molecular dynamics simulations are performed to validate the iSAFT
      results. Our results provide insight into the phase behavior of dendrimer
      solutions as well as guidance in practical applications.

PMID- 30111129
TI  - All-atom computations with irreversible Markov chains.
AB  - We apply the irreversible event-chain Monte Carlo (ECMC) algorithm to the
      simulation of dense all-atom systems with long-range Coulomb interactions. ECMC
      is event-driven and exactly samples the Boltzmann distribution. It neither uses
      time-step approximations nor spatial cutoffs on the range of the interaction
      potentials. Most importantly, it need not evaluate the total Coulomb potential
      and thus circumvents the major computational bottleneck of traditional
      approaches. It only requires the derivatives of the two-particle Coulomb
      potential, for which we discuss mutually consistent choices. ECMC breaks up the
      total interaction potential into factors. For particle systems made up of neutral
      dipolar molecules, we demonstrate the superior performance of dipole-dipole
      factors that do not decompose the Coulomb potential beyond the two-molecule
      level. We demonstrate that these long-range factors can nevertheless lead to
      local lifting schemes, where subsequently moved particles are mostly close to
      each other. For the simple point-charge water model with flexible molecules
      (SPC/Fw), which combines the long-ranged intermolecular Coulomb potential with
      hydrogen-oxygen bond-length vibrations, a flexible hydrogen-oxygen-hydrogen bond
      angle, and Lennard-Jones oxygen-oxygen potentials, we break up the potential into
      factors containing between two and six particles. For this all-atom liquid-water
      model, we demonstrate that the computational complexity of ECMC scales very well
      with the system size. This is achieved in a pure particle-particle framework,
      without the interpolating mesh required for the efficient implementation of other
      modern Coulomb algorithms. Finally, we discuss prospects and challenges for ECMC
      and outline several future applications.

PMID- 30111130
TI  - Diffusion mechanism for highly compressed microgel particles.
AB  - It is argued that Voronoi tessellation theory can be used to model the observed
      diffusion of microgel particles in a highly compressed microgel colloid. It is
      shown that this model is able to account for the fact that even when the microgel
      colloid is highly compressed, the particles can diffuse, while the diffusion rate
      decreases as the degree of compression of the microgel colloid increases, as
      observed.

PMID- 30111131
TI  - Interplay of structure and diffusion in ternary liquid mixtures of benzene +
      acetone + varying alcohols.
AB  - The Fick diffusion coefficient matrix of ternary mixtures containing benzene +
      acetone + three different alcohols, i.e., methanol, ethanol, and 2-propanol, is
      studied by molecular dynamics simulation and Taylor dispersion experiments.
      Aiming to identify common features of these mixtures, it is found that one of the
      main diffusion coefficients and the smaller eigenvalue do not depend on the type
      of alcohol along the studied composition path. Two mechanisms that are
      responsible for this invariant behavior are discussed in detail, i.e., the
      interplay between kinetic and thermodynamic contributions to Fick diffusion
      coefficients and the presence of microscopic heterogeneities caused by hydrogen
      bonding. Experimental work alone cannot explain these mechanisms, while present
      simulations on the molecular level indicate structural changes and uniform
      intermolecular interactions between benzene and acetone molecules in the three
      ternary mixtures. The main diffusion coefficients of these ternary mixtures
      exhibit similarities with their binary subsystems. Analyses of radial
      distribution functions and hydrogen bonding statistics quantitatively evidence
      alcohol self-association and cluster formation, as well as component segregation.
      Furthermore, the excess volume of the mixtures is analyzed in the light of
      intermolecular interactions, further demonstrating the benefits of the
      simultaneous use of experiment and simulation. The proposed framework for
      studying diffusion coefficients of a set of ternary mixtures, where only one
      component varies, opens the way for further investigations and a better
      understanding of multicomponent diffusion. The presented numerical results may
      also give an impulse to the development of predictive approaches for
      multicomponent diffusion.

PMID- 30111132
TI  - Anharmonic vibrational eigenfunctions and infrared spectra from semiclassical
      molecular dynamics.
AB  - We describe a new approach based on semiclassical molecular dynamics that allows
      simulating infrared absorption or emission spectra of molecular systems with
      inclusion of anharmonic intensities. This is achieved from semiclassical power
      spectra by computing first the vibrational eigenfunctions as a linear combination
      of harmonic states, and then the oscillator strengths associated with the
      vibrational transitions. We test the approach against a 1D Morse potential and
      apply it to the water molecule with results in excellent agreement with discrete
      variable representation quantum benchmarks. The method does not require any grid
      calculations, and it is directly extendable to high dimensional systems. The
      usual exponential scaling of the basis set size with the dimensionality of the
      system can be avoided by means of an appropriate truncation scheme. Furthermore,
      the approach has the advantage to provide IR spectra beyond the harmonic
      approximation without losing the possibility of an intuitive assignment of
      absorption peaks in terms of normal modes of vibration.

PMID- 30111133
TI  - Glassy dynamics of two poly(ethylene glycol) derivatives in the bulk and in
      nanometric confinement as reflected in its inter- and intra-molecular
      interactions.
AB  - The inter- and intra-molecular interactions as they evolve in the course of
      glassy solidification are studied by broadband dielectric-and Fourier-transform
      infrared-spectroscopy for oligomeric derivatives of poly(ethylene glycol)
      derivatives, namely, poly(ethylene glycol) phenyl ether acrylate and
      poly(ethylene glycol) dibenzoate in the bulk and under confinement in nanoporous
      silica having mean pore diameters 4, 6, and 8 nm, with native and silanized inner
      surfaces. Analyzing the spectral positions and the oscillator strengths of
      specific IR absorption bands and their temperature dependencies enables one to
      trace the changes in the intra-molecular potentials and to compare it with the
      dielectrically determined primarily inter-molecular dynamics. Special emphasis is
      given to the calorimetric glass transition temperature Tg and Talphabeta ~
      1.25Tg, where characteristic changes in conformation appear, and the secondary
      beta-relaxation merges with the dynamic glass transition (alpha-relaxation).
      Furthermore, the impact of main chain conformations, inter- and intra-molecular
      hydrogen bonding, and nanometric confinement on the dynamic glass transition is
      unraveled.

PMID- 30111134
TI  - 14N overtone nuclear magnetic resonance of rotating solids.
AB  - By irradiating and observing at twice the 14N Larmor frequency, overtone (OT)
      nuclear magnetic resonance (NMR) is capable of obtaining 14NOT spectra without
      first-order quadrupolar broadening. Direct excitation and detection of the
      usually "forbidden" double-quantum transition is mediated by the perturbation
      from the large quadrupole interaction to the spin states quantized by the Zeeman
      interaction. A recent study [L. A. O'Dell and C. I. Ratcliffe, Chem. Phys. Lett.
      514, 168 (2011)] has shown that 14NOT NMR under magic-angle spinning (MAS) can
      yield high-resolution spectra with typical second-order quadrupolar line shapes
      allowing the measurement of 14N chemical shift and quadrupolar coupling
      parameters. This article has also shown that under MAS the main 14NOT peak is
      shifted by twice the sample spinning frequency with respect to its static
      position. We present the theory of 14NOT NMR of static or rotating samples and
      the physical picture of the intriguing spinning-induced shift in the second case.
      We use perturbation theory for the case of static samples and Floquet theory for
      rotating samples. In both cases, the results can be described by a so-called OT
      parameter that scales down the 14NOT radio-frequency (rf) excitation and signal
      detection. This OT parameter shows that the components of the rf field, which are
      transverse and longitudinal with respect to the magnetic field, are both
      effective for 14NOTrf excitation and signal detection. In the case of MAS at
      angular frequency omegar , the superposition of the excitation and detection
      components in the OT parameter makes either the +2omegar or -2omegar term the
      dominant 14NOT signal, depending on the sense of sample spinning with respect to
      the magnetic field. This leads to an apparent 14NOT signal shifted at twice the
      spinning frequency. The features of 14NOT NMR spectra for both static and
      rotating samples are illustrated with simulations. The spinning induced shift and
      its dependence on the spinning direction are confirmed experimentally by
      reversing the spinning direction and the field of the 36 T series-connected
      hybrid magnet at the US National High Magnetic Field Laboratory.

PMID- 30111135
TI  - Extension of the atom by atom scheme of counterpoise method and presentation of
      its new advantages.
AB  - In this paper, for the first time, we want to clearly show that two types of
      binding energies, cited here as interaction energies (IEs) and stabilization
      energies (SEs), may need different values of basis set superposition error (BSSE)
      corrections. We also report the first calculation of the BSSE correction for the
      strain energies (ES) of supermolecular systems. For this purpose, the known atom
      by atom scheme of the counterpoise method was extended to mathematically show
      that the values of BSSE for IE versus SE of a defined system can be really
      different. Then the IE and SE values of some AB and ABC supermolecules were
      corrected for BSSE, calculated through the full counterpoise method (CPn) versus
      its atom by atom scheme (CPaa). The data confirmed that the CPaa accurately gives
      the different BSSE values for IE versus SE when there is a noticeable difference
      between the values of these energies. In the above case, the CPn method that
      gives a single value of BSSE for both IE and SE is not a suitable choice for
      correcting the SE values.

PMID- 30111136
TI  - Understanding the microscopic origin behind heterogeneous properties of water
      confined in and around Abeta17-42 protofilaments.
AB  - Aggregation of amyloid beta (Abeta) peptides in the brain is responsible for one
      of the most devastating neurodegenerative diseases, namely, Alzheimer's disease.
      In this study, we have carried out atomistic molecular dynamics simulations to
      explore the effects of non-uniform structural distortions of Abeta17-42 pre
      fibrillar aggregates of different sizes on the microscopic structure and ordering
      of water molecules confined within their amphiphilic nanocores. The calculations
      revealed non-uniform peptide-water interactions resulting in simultaneous
      existence of both highly ordered and disordered water molecules within the
      spatially heterogeneous confined environment of the protofilament cores. It is
      found that the high degree of ordering originates from a sizable fraction of
      doubly coordinated core water molecules, while the randomly oriented ones are
      those that are coordinated with three neighbors in their first coordination
      shells. Furthermore, it is quantitatively demonstrated that relative fractions of
      these two types of water molecules are correlated with the protofilament core
      topology and the degree of confinement within that. It is proposed that the
      ordered core waters are likely to stabilize the Abeta protofilaments by screening
      the residue charges and favoring water-mediated salt bridge formations, while the
      randomly oriented ones can drive further growth of the protofilaments by being
      displaced easily during the docking of additional peptides. In that way, both
      types of core water molecules can play equally important roles in controlling the
      growth and stability of the Abeta-aggregates.

PMID- 30111137
TI  - General theory of photoexcitation induced photoelectron circular dichroism.
AB  - The photoionization of chiral molecules prepared in a coherent superposition of
      excited states can give access to the underlying chiral coherent dynamics in a
      procedure known as photoexcitation induced photoelectron circular dichroism
      (PXECD). As in photoelectron circular dichroism (PECD), chirality manifests as
      asymmetric photoelectron emission in the forward/backward direction (relative to
      the laser propagation direction). However, in PXECD, the asymmetric photoemission
      is additionally contingent on coherence. This exclusive dependence on coherence
      can also be seen in a different part of the photoelectron angular distribution
      (PAD), where it is not contingent on the chirality of the molecule, thus allowing
      extension of PXECD's sensitivity to tracking coherence to non-chiral molecules.
      Here we present a general theory of PXECD based on angular momentum algebra and
      derive explicit expressions for all pertinent asymmetry parameters which arise
      for the arbitrary polarization of pump (which prepares the superposition of
      excited states) and ionizing probe pulses. The theory is developed in a way that
      clearly and simply separates chiral and non-chiral contributions to the PAD and
      also demonstrates how PXECD and PECD-type contributions, which may be
      distinguished by whether the pump or ionizing probe pulse enables chiral
      response, are mixed when arbitrary polarization is used.

PMID- 30111138
TI  - Energy of the quasi-free electron in CO and HD: Probing intermolecular potentials
      within the local Wigner-Seitz model.
AB  - We present the quasi-free electron energy V0(rho) in the weakly polar fluids CO
      and HD from gas to liquid densities rho, on noncritical isotherms, and at a
      temperature near the critical isotherm. These results represent the first
      systematic investigation of V0(rho) in polar fluids across a broad density range
      and illustrate that field enhanced photoemission can be used to obtain data in
      such systems. We show that the local Wigner-Seitz model for V0(rho), when coupled
      with thermodynamic data for the fluids, can yield optimized intermolecular
      potential parameters, as well as the magnitude of the zero kinetic energy
      electron scattering length.

PMID- 30111139
TI  - Photoelectron spectra of copper oxide cluster anions from first principles
      methods.
AB  - We present results and analyses for the photoelectron spectra of small copper
      oxide cluster anions (CuO-, Cu O2- , Cu O3- , and Cu2O-). The spectra are
      computed using various techniques, including density functional theory (DFT) with
      semi-local, global hybrid, and optimally tuned range-separated hybrid
      functionals, as well as many-body perturbation theory within the GW approximation
      based on various DFT starting points. The results are compared with each other
      and with the available experimental data. We conclude that as in many metal
      organic systems, self-interaction errors are a major issue that is mitigated by
      hybrid functionals. However, these need to be balanced against a strong role of
      non-dynamical correlation-especially in smaller, more symmetric systems-where
      errors are alleviated by semi-local functionals. The relative importance of the
      two phenomena, including practical ways of balancing the two constraints, is
      discussed in detail.

PMID- 30111140
TI  - Influence of surface commensurability on the structure and relaxation dynamics of
      a confined monatomic fluid.
AB  - Molecular dynamics simulations are carried out for a single component, monatomic
      Lennard-Jones fluid confined between two mica surfaces to investigate the
      structure and relaxation dynamics of the confined fluid as a function of surface
      separation. Due to the underlying symmetry of the potassium ions on the mica
      surface, the contact layers prefer to adopt an incommensurate square or rhombic
      symmetry. The inner layers adopt a symmetry varying between rhombic, triangular,
      and square, depending on the density and surface separation. When the surface
      separation is an integral multiple of the particle diameter, distinct layering is
      observed, whereas jammed layers are formed at intermediate surface separations.
      This leads to the formation of both commensurate and incommensurate layering with
      varying intralayer symmetry. The self-intermediate scattering function exhibits a
      gamut of rich dynamics ranging from a distinct two-step relaxation indicative of
      glassy dynamics to slow relaxation processes where the correlations do not relax
      to zero over a microsecond for specific surface separations. An extended beta
      relaxation is observed for both commensurate and incommensurate layering.
      Stretched exponential fits are used to obtain the relaxation times for the late
      alpha-relaxation regime of the self-intermediate scattering function. In some
      cases, we also observed dynamic and structural heterogeneities within individual
      layers. Although a single-component Lennard-Jones fluid does not exhibit a glass
      transition in the bulk, this study reveals that such a fluid can display, without
      supercooling, complex relaxation dynamics with signatures of a fluid approaching
      a glass transition upon confinement at constant temperature.

PMID- 30111141
TI  - Role of electronic thermal transport in amorphous metal recrystallization: A
      molecular dynamics study.
AB  - Recrystallization of glasses is important in a wide range of applications
      including electronics and reactive materials. Molecular dynamics (MD) has been
      used to provide an atomic picture of this process, but prior work has neglected
      the thermal transport role of electrons, the dominant thermal carrier in metallic
      systems. We characterize the role of electronic thermal conductivity on the
      velocity of recrystallization in Ni using MD coupled to a continuum description
      of electronic thermal transport via a two-temperature model. Our simulations show
      that for strong enough coupling between electrons and ions, the increased thermal
      conductivity removes the heat from the exothermic recrystallization process more
      efficiently, leading to a lower effective temperature at the recrystallization
      front and, consequently, lower propagation velocity. We characterize how electron
      phonon coupling strength and system size affect front propagation velocity.
      Interestingly, we find that initial recrystallization velocity increases with
      decreasing system size due to higher overall temperatures. Overall, we show that
      a more accurate description of thermal transport due to the incorporation of
      electrons results in better agreement with experiments.

PMID- 30111142
TI  - Benchmarking of GGA density functionals for modeling structures of nanoporous,
      rigid and flexible MOFs.
AB  - The adequate choice of the interaction model is essential to reproduce
      qualitatively and estimate quantitatively the experimentally observed
      characteristics of materials or phenomena in computer simulations. Here we
      present the results of a benchmarking of density-functional theory calculations
      of rigid and flexible metal-organic frameworks (MOFs). The stability of these
      systems depends on the dispersion interactions. We compare the performance of two
      functionals, Perdew-Burke-Ernzerhof (PBE) and PBE designed for solids, with and
      without the dispersion corrections (D2 and TS), in reproducing the high-accuracy
      low-temperature X-ray and neutron diffraction data for both groups of MOFs. We
      focus our analysis on the key structural parameters: the lattice parameters, bond
      lengths, and angles. We show that the dispersion long range correction is
      essential to stabilize the structures and, in some cases, to converge the system
      to a geometry that is in line with the experimentally observed structure,
      especially for breathing MIL-53 structures or zeolitic imidazolate frameworks. We
      find that for all structures and all analyzed parameters, the D2-corrected PBE
      functional performs the best, except for bonds involving the metal ions; however,
      even for these bonds the difference between the experimentally observed and
      calculated lengths is small. Therefore, we recommend the use of the PBE-D2
      functional in further numerical analyses of rigid and flexible nanoporous MOFs.

PMID- 30111143
TI  - Harmonizing accuracy and efficiency: A pragmatic approach to fragmentation of
      large molecules.
AB  - Fragmentation methods offer an attractive alternative for ab initio treatment of
      large molecules and molecular clusters. However, balancing the accuracy and
      efficiency of these methods is a tight-rope-act. With this in view, we present an
      algorithm for automatic molecular fragmentation within Molecular Tailoring
      Approach (MTA) achieving this delicate balance. The automated code is tested out
      on a variety of molecules and clusters at the Hartree-Fock (HF)- and Moller
      Plesset second order perturbation theory as well as density functional theory
      employing augmented Dunning basis sets. The results show remarkable accuracy and
      efficiency vis-a-vis the respective full calculations. Thus the present work
      forms an important step toward the development of an MTA-based black box code for
      implementation of HF as well as correlated quantum chemical calculations on large
      molecular systems.

PMID- 30111144
TI  - Accurate computation of X-ray absorption spectra with ionization potential
      optimized global hybrid functional.
AB  - This manuscript presents the first consistent ionization potential (IP) optimized
      global hybrid functional to accurately estimate the vertical ionization and
      excitation energies of the inner-shell electrons in molecules. The new method
      fulfills the IP theorem that the Kohn-Sham eigenvalues of all the occupied
      orbitals (including the core orbitals) are good approximations to the exact
      vertical ionization energies. The accuracy of the one-particle spectrum is
      essential to enabling the one-particle density functional theory (DFT) to provide
      accurate results. Compared to its precursor, the range-separated hybrid
      functional CAM-QTP00, the new method is more computationally efficient. The IP
      theorem enables the new method to provide inner-shell ionization energies
      measured by X-ray photoelectron spectroscopy, and it can further accurately
      simulate the X-ray absorption spectrum (XAS, or NEXAFS). The simulated spectra
      can be compared to the experiment directly without shifting. In addition, the new
      method reduces the delocalization error (many-electron self-interaction error)
      which is a severe problem in DFT.

PMID- 30111146
TI  - Rotational (de-)excitation of isocyanogen by collision with helium at low
      energies.
AB  - Isocyanogen, CNCN, was discovered very recently in the interstellar medium (ISM).
      At present, the rate coefficients for the rotational (de-)excitation of CNCN by
      collisions with He are determined. First, we mapped the interaction potential
      between CNCN and He in Jacobi coordinates using highly correlated ab initio
      methodology. Then, an analytical expansion of the CNCN-He potential energy
      surface is derived. Later on, quantum dynamical treatments of nuclear motions are
      performed using the close coupling technique. We obtained the cross sections for
      the rotational (de-)excitation of CNCN after a collision by He up to 2000 cm-1
      total energies. These cross sections are used to deduce the collision rates in
      the 10-300 K range. These data are needed for modeling the CNCN abundances in the
      ISM. This work should help for determining the abundance of such non-symmetrical
      dicyanopolyynes in astrophysical media and indirectly the symmetric one [Cyanogen
      (NCCN)].

PMID- 30111145
TI  - Formation of CO2 from formic acid through catalytic electron channel.
AB  - Low energy electrons can initiate and control chemical reactions through resonant
      attachment forming an electron-molecule compound state. Recently, it has been
      theoretically shown that free electrons can also act as catalysts in chemical
      reactions. We investigate this novel concept for the case of conversion of formic
      acid into CO2. Resonant production of CO2 from cold formic acid films by low
      energy electron impact is observed using Fourier transform infrared spectroscopy.
      The resonant peak observed at 6 eV is identified as the catalytic electron
      channel. The experimental results are augmented with the ab initio quantum
      chemical calculations.

PMID- 30111147
TI  - Mechanistic study of the photoexcitation, photoconversion, and photodissociation
      of CS2.
AB  - Carbon disulfide is a prototype molecular system for studies of photophysical
      processes in molecules at different time scales and is also relevant to
      astrophysics. Here, reliable molecular properties are computed for linear SCS,
      bent cyc-CS2, and linear CSS forms using highly correlated post Hartree-Fock
      methods in conjunction with large basis sets. Structures are identified using
      explicitly correlated and standard coupled cluster techniques. Evolution of the
      lowest-lying singlet and triplet electronic states of the three isomers along the
      SS and CS stretching coordinates and along the bending angle are mapped at the
      multireference configuration interaction (MRCI)/aug-cc-pV(5+d)Z level of theory.
      The computations suggest that the 1B2(1Sigma+) electronic state of the SCS isomer
      plays an important role in the photoconversion of CS2 to cyc-CS2 and CSS.
      Photoconversion competes with photodissociation. Plausible mechanisms for the
      production of S2 and CS diatomics after the photoexcitation of SCS are proposed.
      To aid in the identification of CSS in the laboratory and in astrophysical media,
      a set of spectroscopic constants and rovibrational levels for CSS are reported.

PMID- 30111148
TI  - Three-dimensional phase field modeling of inhomogeneous gas-liquid systems using
      the PeTS equation of state.
AB  - Recently, an equation of state (EoS) for the Lennard-Jones truncated and shifted
      (LJTS) fluid has become available. As it describes metastable and unstable states
      well, it is suited for predicting density profiles in vapor-liquid interfaces in
      combination with density gradient theory (DGT). DGT is usually applied to
      describe interfaces in Cartesian one-dimensional scenarios. In the present work,
      the perturbed LJ truncated and shifted (PeTS) EoS is implemented into a three
      dimensional phase field (PF) model which can be used for studying inhomogeneous
      gas-liquid systems in a more general way. The results are compared with the
      results from molecular dynamics simulations for the LJTS fluid that are carried
      out in the present work and good agreement is observed. The PF model can
      therefore be used to overcome the scale limit of molecular simulations. A finite
      element approach is applied for the implementation of the PF model. This requires
      the first and second derivatives of the PeTS EoS which are calculated using hyper
      dual numbers. Several tests and examples of applications of the new PeTS PF model
      are discussed.

PMID- 30111149
TI  - Spin-selective electron transfer reactions of radical pairs: Beyond the Haberkorn
      master equation.
AB  - Radical pair recombination reactions are normally described using a quantum
      mechanical master equation for the electronic and nuclear spin density operator.
      The electron spin state selective (singlet and triplet) recombination processes
      are described with a Haberkorn reaction term in this master equation. Here we
      consider a general spin state selective electron transfer reaction of a radical
      pair and use Nakajima-Zwanzig theory to derive the master equation for the spin
      density operator, thereby elucidating the relationship between non-adiabatic
      reaction rate theory and the Haberkorn reaction term. A second order perturbation
      theory treatment of the diabatic coupling naturally results in the Haberkorn
      master equation with an additional reactive scalar electron spin coupling term.
      This term has been neglected in previous spin chemistry calculations, but we show
      that it will often be quite significant. We also show that beyond the second
      order in perturbation theory, i.e., beyond the Fermi golden rule limit, an
      additional reactive singlet-triplet dephasing term appears in the master
      equation. A closed form expression for the reactive scalar electron spin coupling
      in terms of the Marcus theory parameters that determine the singlet and triplet
      recombination rates is presented. By performing simulations of radical pair
      reactions with the exact hierarchical equations of motion method, we demonstrate
      that our master equations provide a very accurate description of radical pairs
      undergoing spin-selective non-adiabatic electron transfer reactions. The
      existence of a reactive electron spin coupling may well have implications for
      biologically relevant radical pair reactions such as those which have been
      suggested to play a role in avian magnetoreception.

PMID- 30111150
TI  - Coupled-cluster based basis sets for valence correlation calculations. New
      primitives, frozen atomic natural orbitals, and basis sets from double to
      hextuple zeta for atoms H, He, and B-Ne.
AB  - A series of new basis sets generated from coupled-cluster theory are presented.
      Sets of primitive Gaussians for angular momentum shells containing occupied
      orbitals are optimized and extended until the Hartree-Fock energy improvement per
      electron falls below 10 MUH. This same energy threshold is applied to the energy
      from the coupled-cluster singles, doubles, and perturbative triples (CCSD(T))
      approximation and taken as a guide to the generation of sets of polarization
      functions, constructed at the level of second-order many-body perturbation
      theory, once it is shown that practically indistinguishable results are obtained
      if the more costly CCSD(T) approach is used. A variant of the usual atomic
      natural orbitals (ANOs) grounded on the frozen natural orbital idea is explored,
      leading to the frozen ANO (FANO) contraction scheme, whose truncation pattern and
      convergence capabilities are thoroughly tested. Due to its superior description
      of the single determinant solution, the FANOs are proposed as the recommended
      contraction approach. FANO basis sets of sizes ranging from double to hextuple
      zeta are provided for atoms H through Ne and examined in atomic and molecular
      calculations.

PMID- 30111151
TI  - Application of optimal control simulation to selective photodissociation of IBr
      by non-resonant dynamic Stark effects.
AB  - We apply nonlinear optimal control simulation to design a non-resonant control
      pulse that maximizes the probability of specified photodissociation of IBr by
      utilizing the non-resonant dynamic Stark effect in the presence of a
      predetermined pump pulse. The optimal pulses are always composed of several
      subpulses that increase the target probability considerably depending on the
      wavelength of the pump pulse. Focusing on the cases of high target probabilities,
      we systematically examine how the subpulses cooperate with each other on the
      basis of pulse-partitioning analyses. We show that the subpulses largely
      cooperate with the pump pulse, which can explain their irradiation timings. On
      the other hand, the cooperation between the subpulses is mainly expressed as the
      sum of the contribution from each subpulse.

PMID- 30111152
TI  - Stochastic sampling of the isothermal-isobaric ensemble: Phase diagram of
      crystalline solids from molecular dynamics simulation.
AB  - A methodology to sample the isothermal-isobaric ensemble using Langevin dynamics
      is proposed, which combines novel features of geometric integrators for the
      equations of motion. By employing the Trotter expansion, the methodology
      generates a robust, symmetric, and accurate numerical algorithm. In order to show
      that the proposed method correctly samples the phase-space, simulations in the
      isotropic NPT ensemble were carried out for two analytical examples. Also this
      method lets us study a solid-solid phase transition by conducting a fully
      flexible-cell molecular dynamics simulation. Additionally, we present an
      efficient method to determine the Gibbs free energy in a wide interval of
      pressure along an isothermal path, which allows us to determine the transition
      pressure in a driven by pressure solid-solid phase transition. Our calculations
      show that the methodology is highly suitable for the study of the phase diagram
      of crystalline solids.

PMID- 30111153
TI  - Steady-state reaction rate of diffusion-controlled reactions in sheets.
AB  - In many biological situations, a species arriving from a remote source diffuses
      in a domain confined between two parallel surfaces until it finds a binding
      partner. Since such a geometric shape falls in between two- and three-dimensional
      settings, the behavior of the macroscopic reaction rate and its dependence on
      geometric parameters are not yet understood. Modeling the geometric setup by a
      capped cylinder with a concentric disk-like reactive region on one of the lateral
      surfaces, we provide an exact semi-analytical solution of the steady-state
      diffusion equation and compute the diffusive flux onto the reactive region. We
      explore the dependence of the macroscopic reaction rate on the geometric
      parameters and derive asymptotic results in several limits. Using the self
      consistent approximation, we also obtain a simple fully explicit formula for the
      reaction rate that exhibits a transition from two-dimensional to three
      dimensional behavior as the separation distance between lateral surfaces
      increases. Biological implications of these results are discussed.

PMID- 30111154
TI  - Microscopic density functional theory for monolayers of diblock copolymers.
AB  - We propose density functional theory for diblock copolymers in two dimensions.
      Our theoretical framework is based on Wertheim's first order thermodynamic
      perturbation theory. Using the proposed approach, we investigate the structure
      and phase behavior of monolayers of symmetric diblock copolymers. We find that
      the phase behavior of symmetric diblock copolymer monolayers is similar to that
      in 3D. This includes the scaling of the equilibrium lamellar width with chain
      length. We find that the topology of the resulting phase diagrams depends on the
      chain length and the unlike segment interaction incompatibility and involves
      either one, two, or three triple points (one of them being the peritectic point).
      We expect that a similar phase behavior could be obtained for monolayers of
      colloidal suspensions with carefully tuned interparticle interactions.

PMID- 30111155
TI  - Selected configuration interaction dressed by perturbation.
AB  - Selected configuration interaction (sCI) methods including second-order
      perturbative corrections provide near full CI (FCI) quality energies with only a
      small fraction of the determinants of the FCI space. Here, we introduce both a
      state-specific and a multi-state sCI method based on the configuration
      interaction using a perturbative selection made iteratively (CIPSI) algorithm.
      The present method revises the reference (internal) space under the effect of its
      interaction with the outer space via the construction of an effective
      Hamiltonian, following the shifted-Bk philosophy of Davidson and co-workers. In
      particular, the multi-state algorithm removes the storage bottleneck of the
      effective Hamiltonian via a low-rank factorization of the dressing matrix.
      Illustrative examples are reported for the state-specific and multi-state
      versions.

PMID- 30111156
TI  - Diffusion processes in a poly-crystalline zeolitic material: A molecular dynamics
      study.
AB  - Extensive molecular dynamics simulations of xenon in two classes of zeolite
      crystal systems, one consisting of purely intra-crystalline space and the other
      with both intra- and inter-crystalline space are reported. The latter mimics a
      typical poly-crystalline sample of zeolite. Comparison of results from these two
      systems provides insights into the structure and dynamics in the presence of
      inter-crystalline space. The temperature, as well as the distance between the
      crystallites, has been varied. The density distribution and diffusivities
      calculated inside the poly-crystalline system show that the interfacial region
      between the crystal and the inter-crystalline region acts as a bottleneck for
      diffusion through the system. At lower temperatures, the particles are trapped at
      the interface due to the pronounced energy minima present in that region. With
      the increase in temperature, the particles are able to overcome this barrier
      frequently, and the transport across the inter-crystalline region is increased. A
      ballistic or superdiffusive motion is seen in the inter-crystalline region along
      all the axes except along the axis which has the inter-crystalline space. The
      transition time for ballistic to diffusive motion increases with the increase in
      the length of the inter-crystalline space. Velocity auto- and cross correlation
      functions exhibit strong oscillations and exchange of kinetic energy along
      directions perpendicular to the direction of the inter-crystalline space. These
      results explain why uptake and PFG-NMR measurements exhibit lower values for
      diffusivity for the same system when compared to Quasi-Elastic Neutron
      Scattering. Thus, using molecular dynamics simulations, we were able to correlate
      the difference of diffusivity values measured using various experimental methods
      where these inter-crystalline regions are common.

PMID- 30111157
TI  - Using an iterative eigensolver and intertwined rank reduction to compute
      vibrational spectra of molecules with more than a dozen atoms: Uracil and
      naphthalene.
AB  - We use a direct product basis, basis vectors computed by evaluating matrix-vector
      products, and rank reduction to calculate vibrational energy levels of uracil and
      naphthalene, with 12 and 18 atoms, respectively. A matrix representing the
      Hamiltonian in the direct product basis and vectors with as many components as
      there are direct product basis functions are neither calculated nor stored. We
      also introduce an improvement of the Hierarchical Intertwined Reduced-Rank Block
      Power Method (HI-RRBPM), proposed previously in Thomas and Carrington, Jr. [J.
      Chem. Phys. 146, 204110 (2017)]. It decreases the memory cost of the HI-RRBPM and
      enables one to compute vibrational spectra of molecules with over a dozen atoms
      with a typical desktop computer.

PMID- 30111158
TI  - Barriers and facilitators to effective tuberculosis infection control practices
      in Madang Province, PNG - a qualitative study.
AB  - INTRODUCTION: Tuberculosis (TB) remains a major public health problem in many
      countries. There is a greater threat of exposure to TB in congregate settings
      including healthcare facilities, prisons and households where health workers
      treat patients with TB. In healthcare facilities, the key areas of risk of
      infection include settings where people with undiagnosed TB, including multidrug
      resistant TB, congregate, such as outpatient waiting areas, pathology waiting
      areas, radiology departments and pharmacies, and wards where untreated patients
      await investigation results. With high levels of TB in the community, and
      symptoms leading people to seek treatment, health services can be TB 'hot spots',
      and in the absence of good TB infection control (TBIC) a clinical service may
      actually promote the spread of TB, rather than contain it. Practical and relevant
      control measures are, therefore, necessary to monitor the spread of TB. METHODS:
      The purpose of this hermeneutic phenomenological research was to explore rural
      health workers' perspectives of barriers and facilitators to effective TBIC
      practices in rural health facilities in Madang Province, Papua New Guinea (PNG).
      The conceptual framework was adopted from WHO policy on TBIC in healthcare
      facilities, congregate settings and households as a benchmark to guide the study.
      Qualitative individual and group interviews (with an average time of 30 minutes)
      and field notes were conducted with 12 key informants comprising clinicians (n=9)
      and support staff (n=3) from the health facilities. Trustworthy steps were taken
      during the semi-structured interview to ensure data validity through member check
      and repeating participants' narratives to ensure accurate representation of
      participants' experiences. All interviews and field notes were analysed using
      standard phenomenological methods. RESULTS: The findings showed that numerous
      interconnected factors have influenced the implementation of TBIC measures in the
      rural health facilities in Madang Province. They include issues related to
      inadequacies in the healthcare systems, access to personal protective equipment,
      separation procedures, sputum status, monitoring and control, training, and
      health services as TB 'hot spots'. CONCLUSIONS: The study found evidence that
      health system factors do impact on the capacity to implement TBIC. Further,
      factors beyond TBIC such as sociocultural factors have an important influence on
      the way TBIC is implemented. The results of this study are useful for clinicians,
      health administrators and policymakers to improve the interventions and
      application of TBIC procedures at the rural health facilities in PNG. The study
      is limited to health services in Madang Province, and therefore the findings
      cannot automatically be generalised to other district hospitals and health
      centres in other parts of PNG. However, the WHO TBIC is a standardised policy and
      the results of the findings may be useful for other health facilities that manage
      TB patients in PNG and for future health systems researchers to help improve the
      generalisability of the findings. Further research is needed to explore health
      workers' experiences of conditions, actions and everyday practical issues
      affecting the application of TBIC measures in the rural health facilities of PNG.

PMID- 30111159
TI  - Low uptake of HIV testing among male clients of female sex workers in China.
AB  - Male client of female sex workers (MCFSW) is a sizable population transmitting
      HIV from high-risk population to female general population in China. This study
      was to investigate the prevalence of taking up any forms of HIV testing in
      lifetime and in the past year among MCFSW in Hong Kong. Factors associated with
      uptake of any forms HIV testing in the past year were also investigated. A cross
      sectional survey was conducted. Participants were Hong Kong Chinese males aged
      >=18 years, and self-reported had patronized at least one female sex workers
      (FSW) in the last six months. A total of 303 MCFSW recruited online (n = 160) or
      from venues (n = 143) completed the self-administered questionnaire. Logistic
      regression was used for data analysis. The prevalence of taking up any forms of
      HIV testing in lifetime and last year was 49.2% and 23.8%, respectively.
      Adjusting for these background variables, scale scores representing perceived
      severity of HIV infection (AOR: 1.17), perceived benefits of HIV testing (AOR:
      1.18) and perceived self-efficacy in taking up HIV testing (AOR: 1.36) were
      significantly and positively associated with uptake of any forms of HIV testing
      in the last year, while negative associations were found for the Perceived
      Psychological Barrier Scale (AOR= 0.88) and the Perceived Logistical Barrier
      Scale (AOR: 0.78). MCFSW in Hong Kong reported low uptake of HIV testing. Health
      promotion is urgently needed. Modifying perceptions related to the Health Belief
      Model are potential useful strategies. The potential of using HIV self-testing to
      increase HIV testing coverage among MCFSW should also be considered.

PMID- 30111160
TI  - Prevalence of VIM- and GIM-producing Acinetobacter baumannii from patients with
      severe urinary tract infection.
AB  - Carbapenems are administered as the final drug of choice for treating complicated
      nosocomial infections caused by multidrug-resistant Acinetobacter baumannii
      strains. It is currently a worldwide issue that metallo-beta-lactamases (MBLs) as
      carbapenem-hydrolyzing enzymes are one of the major drug resistance mechanisms.
      This investigation is thus aimed to assess the prevalence and characterize the
      MBL-producing strains of A. baumannii both by phenotypic assays and by genotypic
      characterization. A total of 73 isolates of A. baumannii were phenotypically and
      genotypically characterized from patients (N = 1,000) with severe urinary tract
      infection. Tested strains were subjected to double disc synergy testing (DDST) by
      Kirby-Bauer disc diffusion method with imipenem (IMP) and IMP/EDTA combination
      discs. Plasmid DNA was molecularly screened for MBL-encoding blaIMP, blaVIM,
      blaGIM, and blaNDM genes by PCR for the genetic relatedness of the MBL genes with
      carbapenem resistance. Carbapenem resistance profile showed 100%, 45%, and 49%
      non-susceptibility against imipenem, doripenem, and meropenem, respectively.
      Altogether 42.46% (n = 31) of the isolates showed MBL production upon double disc
      phenotypic test with IMP and IMP/EDTA discs. The blaVIM and blaGIM were detected
      in 34.24% (n = 25) and 16.43% (n = 12) of the isolates, respectively, while the
      co-occurrence of blaVIM and blaGIM was 2.73% among the isolates. DDST-positive
      isolates showed 21.19% and 9.58% strains positive for blaVIM and blaGIM,
      respectively, whereas 1.36% of the strains for both genes. None of the strains
      yielded blaIMP and blaNDM genes. The findings of this study showed prevalence of
      carbapenem resistance among A. baumannii from urine samples and the frequency of
      blaVIM and blaGIM.

PMID- 30111162
TI  - Tongue Reduction Surgery and Feeding Difficulties in Infants With Beckwith
      Wiedemann Syndrome: A Case Series.
AB  - OBJECTIVE: To profile the pre- and post-operative feeding difficulties in infants
      with macroglossia in Beckwith Wiedemann Syndrome (m-BWS) who have had tongue
      reduction surgery (TRS) and to pilot a bespoke feeding rating scale. DESIGN:
      Retrospective consecutive case series designed with two pre-operative and one 3
      month post-operative feeding assessments. A 4-point Likert-type scale was
      developed and applied retrospectively to describe the feeding behaviors for
      liquids, purees, and solids. Descriptive and non-parametric statistics were used.
      SETTING: National service for children with m-BWS at a pediatric hospital.
      PATIENTS: Twenty-five infants, age range 4 to 12 months at initial assessment,
      underwent TRS (median age = 16 months). INTERVENTION: Tongue reduction surgery.
      OUTCOME MEASURE: Oral and selected pharyngeal stage feeding behaviors on liquids,
      purees, and solids. RESULTS: Pre-operative profile: Most feeding difficulties
      arose at the oral stage due to the macroglossia impacting important lingual
      movements. Difficulties were found with lip seal formation, biting, bolus
      manipulation and tongue lateralization. Aspiration risk was found in >75%.
      Texture modification was indicated for purees and solids. Post-operative profile:
      There were statistically significant differences for each consistency pre- and
      post-operatively. Eighty-four percent of infants had age-appropriate drinking and
      eating skills. Mild residual difficulties with biting, tongue lateralization, and
      bolus manipulation remained for solids in four infants. CONCLUSIONS: Feeding
      difficulties are common pre-operatively in m-BWS, putting infants at risk of
      aspiration if left unmanaged. TRS was effective in reducing or eliminating them.
      This is the first systematic report of infant feeding in m-BWS pre- and post-TRS.

PMID- 30111161
TI  - High rate of carbapenem-resistant Klebsiella pneumoniae detected from hospital
      equipments in Iran.
AB  - The objective of this study was to assess the prevalence, antibiogram, and
      related genes of carbapenem-resistant Klebsiella pneumoniae (CRKP) among hospital
      environment samples. A total of 250 samples were taken from different surfaces
      and medical devices of three hospitals in Isfahan, Iran. All samples were
      cultured and K. pneumoniae strains were identified by conventional
      microbiological methods and polymerase chain reaction (PCR). Antibiogram of
      isolates was performed by disk diffusion method and production of carbapenemases
      and metallo-beta-lactamases (MBLs) was confirmed using modified Hodge test and E
      test, respectively. Molecular detection of the related genes was carried out by
      PCR. Overall, 37 (14.8%) K. pneumoniae strains were isolated, of which 34 (91.9%)
      strains were resistant to carbapenems. Twenty-eight (82.4%) isolates were
      positive for carbapenemases and seven (20.6%) isolates were phenotypically MBL
      producers. The results of PCR showed that the prevalence of blaOXA-48, blaNDM,
      blaIMP, blaSHV, blaCTX-M, blaTEM, and class 1 integron among CRKP isolates was
      70.6%, 52.9%, 2.9%, 100%, 82.4%, 55.9%, and 76.5%, respectively. However, blaKPC,
      blaGES, blaIMI, blaVIM, and class 2 integron were not detected in any of the
      isolates. This study showed that the environment of our hospitals is contaminated
      with CRKP and it emphasizes the importance of using standard methods for
      infection control.

PMID- 30111164
TI  - Evaluating Efficacy and Preference for Prompt Type During Discrete-Trial
      Teaching.
AB  - The components of discrete-trial teaching (DTT) may be individualized to each
      learner during instruction (e.g., the type of prompts used). However, there is
      limited research on the relative efficiency and effectiveness of these different
      prompt types. In addition, the learner's preference for how they are taught is
      not always considered. The present study compared relative effectiveness of three
      prompt types (i.e., a gesture, modeling, physical guidance) to a no-prompt
      control condition during a receptive identification task with three boys with
      autism. One participant met the mastery criterion first in the model prompt
      condition, and two participants in the physical prompt condition. All
      participants selected the physical prompt during a concurrent-chains preference
      assessment. In addition, all participants completed a chained task using the most
      effective prompt type.

PMID- 30111163
TI  - Quality of life in HIV-infected Chinese women and their family caregivers: an
      intervention study.
AB  - China is experiencing a rapid increase in the number of HIV-infected women. In
      this study, we describe the development and preliminary evaluation of an
      intervention tailored for Chinese HIV-infected women and caregivers to improve
      their self- and family management, with goals of enhancing their physical quality
      of life (QOL) and decreasing their depressive symptomatology. Forty-one HIV
      infected women and their caregivers were recruited from two premier Chinese
      hospitals from July 2014 through March 2016. Participants were randomized to
      either the control or intervention arm for the Self- and Family Management
      Intervention (SAFMI). Each study dyad in the intervention arm received three
      counseling sessions with a nurse interventionist. At baseline, immediate post
      intervention (month 1) and follow-up (month 3), the participants were assessed by
      a self-reported survey. Generalized Hierarchical Linear Modeling was used to
      evaluate the efficacy of the intervention. Chinese HIV-infected women in the
      intervention arm had significantly higher probability of higher physical QOL at
      month 1 and lower probability of clinically meaningful depressive symptomatology
      at month 3 compared with women in the control arm. In contrast, the effects of
      the intervention were less salient for caregivers. This study represents one of
      the first in China to include family caregivers in HIV management. Feasibility
      and acceptability were high, in that family members were willing to join the
      study, learn about HIV, and practice new skills to support the HIV-infected women
      in their lives. A larger trial is needed to fully evaluate this intervention
      which shows promising preliminary effects in promoting physical QOL and
      decreasing depressive symptomatology among Chinese HIV-infected women.

PMID- 30111165
TI  - Can "Becoming Breastfeeding Friendly" Impact Breastfeeding Protection, Promotion,
      and Support in Mexico? A Qualitative Study.
AB  - BACKGROUND: The Becoming Breastfeeding Friendly (BBF) initiative includes a guide
      that helps countries worldwide assess their readiness to scale up national
      breastfeeding programs. Country committees of breastfeeding experts across
      government, academia, and civil society engage with BBF by applying the BBF
      toolbox that includes (1) the BBF Index (BBFI) to measure and score a country's
      breastfeeding environment, (2) case studies that illustrate how countries have
      created enabling environments for breastfeeding, and (3) a 5-meeting process,
      during which country committees develop policy recommendations intended to
      improve breastfeeding outcomes based on the BBFI scores. OBJECTIVE: This study
      seeks to understand how the application of the BBF toolbox impacted plans to
      improve the enabling environment for breastfeeding in Mexico. METHODS: Semi
      structured interviews were conducted with Mexico's 11 BBF country committee
      members about the 5-meeting process between May and June 2017. Audio recordings
      were transcribed and were coded and analyzed using a grounded theory approach.
      RESULTS: Three major themes emerged: (1) the unique enabling environment for
      breastfeeding consisted of obstacles and opportunities for improvement, (2)
      favorable country committee member dynamics positively affected the utility of
      the BBF toolbox, and (3) BBF revealed and shaped country committee members'
      shared vision of change that laid the foundation for a shared public policy
      agenda. CONCLUSIONS: Becoming Breastfeeding Friendly can generate multisectoral
      breastfeeding champions who can advance the public policy agenda to improve
      breastfeeding outcomes at the national level both in Mexico and elsewhere.

PMID- 30111166
TI  - The oncomir face of microRNA-206: A permanent miR-206 transfection study.
AB  - MiR-206 is a remarkable miRNA because it functions as a suppressor miRNA in
      rhabdomyosarcoma while at the same time, as previously showed, it can act as an
      oncomiRNA in SMARCB1 immunonegative soft tissue sarcomas. The aim of this study
      was to investigate the effect of miR-206 on its several target genes in various
      human tumorous and normal cell lines. In the current work, we created miR-206
      overexpressing cell lines (HT-1080, Caco2, iASC, and SS-iASC) using permanent
      transfection. mRNA expression of the target genes of miR-206 (SMARCB1, ACTL6A,
      CCND1, POLA1, NOTCH3, MET, and G6PD) and SMARCB1 protein expression were examined
      with quantitative real-time polymerase chain reaction, immunoblotting,
      immunocytochemistry, and flow cytometry. MiRNA inhibition was used to validate
      our results. We found a diverse silencing effect of miR-206 on its target genes.
      While an overall tendency of downregulation was noted, expression profiles of
      individual cell lines showed large variability. Only CCND1 and MET were
      consistently downregulated. MiR-206 had an antiproliferative effect on a normal
      human fibroblast cell line. A strong silencing effect of SMARCB1 in miR-206
      transfected SS-iASC was most likely caused by the synergic influence of the SS18
      SSX1 fusion protein and miR-206. In the same cell line, a moderate decrease of
      SMARCB1 protein expression could be observed with immunocytochemistry and flow
      cytometry. In the most comprehensive analysis of miR-206 effects so far, a modest
      but significant downregulation of miR-206 targets on the mRNA level was confirmed
      across all cell lines. However, the variability of the effect shows that the
      action of this miRNA is largely cell context-dependent. Our results also support
      the conception that the oncomiR effect of miR-206 on SMARCB1 plays an important
      but not exclusive role in SMARCB1 immunonegative soft tissue sarcomas so it can
      be considered important in planning the targeted therapy of these tumors in the
      future. Impact statement Mir-206 is a very unique microRNA because it can act as
      a suppressor miRNA or as an oncomiRNA depending on the tumor tissue. In SMARCB1
      negative soft tissue sarcomas miR-206 is overexpressed, so thus in epithelioid
      and synovial sarcomas it functions as an oncomiRNA. MiR-206 has diverse silencing
      effects on its target genes. We found that the action of miR-206 is largely cell
      context dependent. The oncomiR role of miR-206 is crucial but not exclusive in
      SMARCB1 negative soft tissue sarcomas and miR-206 has an antiproliferative effect
      on a normal human fibroblast cell line. Expressions of miR-206 targets observed
      in tumors can only be reproduced in the corresponding tumorous cell lines. This
      is the first study which examined the permanent effect of miR-206 on its target
      genes in normal, tumor, and genetically engineered cell lines.

PMID- 30111167
TI  - Morton's Neuroma Excision: What Are We Really Doing? Which Retractor Is Superior?
AB  - BACKGROUND: When using a dorsal approach for Morton's neuroma excision, the most
      common complication is recurrent Morton's neuroma. The present cadaveric study
      demonstrates how far proximally the nerve is resected during a dorsal approach
      and examines both the laminar spreader and Gelpiretractor to determine which
      instrument facilitates maximal proximal resection of the nerve. METHODS: This
      study involved 12 fresh-frozen cadaver specimens, each of which underwent a
      dorsal approach to the interdigital nerve with proximal resection. Either a
      laminar spreader or a Gelpi retractor was used to improve visualization of the
      intermetatarsal space. The interdigital nerve was then resected, and the lengths
      of the cut nerves were compared based on the retractor employed. RESULTS: The
      mean length of proximal resection in the second intermetatarsal space was 2.42 cm
      when using the laminar spreader and 1.93 cm when using the Gelpi retractor (P =
      .252). In the third intermetatarsal space, the mean length of proximal resection
      was 2.14 cm when using the Laminar spreader and 1.48 cm when using the Gelpi
      retractor (P = .166). CONCLUSION: This study demonstrates how far proximal the
      interdigital nerve is resected during a dorsal approach to Morton's neuroma and
      shows no statistically significant difference between the Laminar spreader and
      the Gelpi retractor. LEVELS OF EVIDENCE: Level V: Cadaver study.

PMID- 30111168
TI  - Amino Acid Profile of Synovial Fluid Following Intra-articular Ankle Fracture.
AB  - BACKGROUND: Post-traumatic osteoarthritis (PTOA) is a frequent complication in
      patients with a previous traumatic joint injury, and the pathophysiology is not
      well understood. The goal of this study was to characterize the biochemical
      signature of amino acids, peptides, and amino acid metabolites in ankle synovial
      fluid following intra-articular fracture. METHODS: Synovial fluid from both the
      injured and contralateral ankles of 19 patients with an intra-articular ankle
      fracture was obtained and analyzed via metabolic profiling. Follow-up analysis
      was performed after 6 months in 7 of these patients. RESULTS: Statistical
      comparisons between injured and contralateral ankles revealed that 19 of the 66
      measured amino acids, peptides, and amino acid metabolites were significantly
      elevated at time of fracture. Metabolites associated with glutathione metabolism
      exhibited the most elevated mean-fold changes, indicating a possible role for
      oxidative stress in fractured ankles. None of the metabolites elevated at
      baseline were significantly elevated after 6 months, but 6 metabolites had mean
      fold changes greater than 2.1 at this time point. Multiple metabolites also
      exhibited significant correlations ( r > 0.575) with matrix metalloproteinase-1
      and -9. CONCLUSION: These results indicate the presence of amino acid metabolic
      products in the setting of ankle fracture and suggest that these changes in amino
      acid metabolism may be chronic and indicate a role for inflammation and collagen
      degradation in disease progression. CLINICAL RELEVANCE: Changes in amino acid
      metabolism following intra-articular fracture may contribute to the progression
      to PTOA. This knowledge may allow for the identification and early treatment of
      patients at risk of developing PTOA. LEVEL OF EVIDENCE: Level III, comparative
      series.

PMID- 30111169
TI  - Plitidepsin: a potential new treatment for relapsed/refractory multiple myeloma.
AB  - Plitidepsin is a marine-derived anticancer compound isolated from the
      Mediterranean tunicate Applidium albicans. It exerts pleiotropic effects on
      cancer cells, most likely by binding to the eukaryotic translation eEF1A2. This
      ultimately leads to cell-cycle arrest, growth inhibition and induction of
      apoptosis via multiple pathway alterations. Recently, a Phase III randomized
      trial in patients with relapsed/refractory multiple myeloma reported outcomes for
      plitidepsin plus dexamethasone compared with dexamethasone. Median progression
      free survival was 3.8 months in the plitidepsin arm and 1.9 months in the
      dexamethasone arm (HR: 0.611; p = 0.0048). Here, we review preclinical data
      regarding plitidepsins mechanism of action, give an overview of clinical trial
      results across different tumor types as well as the latest results in multiple
      myeloma.

PMID- 30111170
TI  - Policy and prevention efforts for gaming should consider a broad perspective.
AB  - Internet gaming disorder is gaining attention around the world. Some efforts have
      been directed toward preventing gaming problems from developing or persisting,
      but few approaches have been empirically evaluated. No known effective prevention
      intervention exists. Reviewing the broader field of prevention research should
      help research and best practices move forward in abating problems that arise from
      excessive gaming.

PMID- 30111172
TI  - Defining the Virtual Patient-Centered Medical Home.

PMID- 30111171
TI  - HIV infection after prenatal screening: an open window leading to perinatal
      infection.
AB  - Despite a dramatic decrease in vertical transmission of HIV in the developed
      world, maternal HIV infection acquired after negative prenatal screening still
      leaves a window of vulnerability. Through quality assurance programs in two
      Canadian Provinces, five cases where perinatal HIV transmission occurred despite
      negative prenatal screening were identified between 2005 and 2015. Maternal risk
      factors such as intravenous drug use, high-risk sexual behavior, hepatitis C
      virus co-infection, and belonging to high prevalence minority groups were common.
      Two mothers had their negative HIV test performed in the first trimester and
      three mothers had negative testing in the third trimester. All babies were
      clinically healthy at delivery with a normal weight. Three babies were tested
      following subsequent identification of maternal HIV infection and two babies
      presented with opportunistic infections leading to their diagnoses. The
      characteristics of these cases suggest that to achieve complete elimination of
      vertical HIV transmission, selective and innovative clinical management of
      mothers at high risk for HIV may be required.

PMID- 30111173
TI  - A 5-Month-Old Female Presenting With Lethargy and Hypoglycemia.

PMID- 30111174
TI  - HIV serostatus disclosure in the Democratic Republic of the Congo: a systematic
      review.
AB  - HIV status disclosure among people living with HIV/AIDS has been shown to have a
      number of both personal and public health benefits, but rates of HIV status
      disclosure remain low in many African countries, including the Democratic
      Republic of the Congo (DRC). This systematic review uses the Disclosure Process
      Model to examine the factors involved in serostatus disclosure and nondisclosure
      to various persons in the lives of people living with HIV/AIDS (PLWHA) in the
      DRC, as well as the specific outcomes of their disclosure or nondisclosure.
      MEDLINE/PubMed, Embase, Web of Science, Global Health, and PsycINFO were searched
      and research studies were included if: (i) the study discussed disclosure of HIV
      status; (ii) the study population included HIV-infected people in DRC; and (iii)
      the study was published in English. Fourteen articles met the inclusion criteria
      and were included in the study. Factors contributing to nondisclosure were
      generally associated with high stigma of HIV in adults and concern for emotional
      wellbeing when disclosing to HIV positive minors. Factors contributing to
      disclosure among adults were increased social support and religion. In disclosing
      to HIV positive minors, increasing age and health benefits were identified as
      approach goals that supported disclosure. The findings highlight the importance
      of understanding the avoidance and approach goals involved in HIV status
      disclosure among populations living in the DRC. Interventions and future research
      directed at increasing HIV disclosure among Congolese PLWHA should move beyond
      individual-level to consider multilevel factors including circumstantial social
      behaviors.

PMID- 30111176
TI  - Parboiling of sorghum grains as a strategy to improve endosperm yield and mineral
      content of refined flours.
AB  - The aims were (i) to optimize the parboiling/decorticating process by assessing
      the effects of parboiling soaking temperature (60-80 C) and pearling time (4-6
      min and 5.5-9.5 min for red and white sorghum) on endosperm yield and ash
      content, to obtain pregelatinized refined flours from parboiling sorghum (RF-PS)
      and (ii) to evaluate the final content of selected nutrients in RF-PS obtained in
      these optimal conditions. Endosperm yield decreased with the increase of pearling
      time, and a maximum around 70 C soaking temperature was observed. Ash content
      decreased with increasing soaking temperature and pearling time. The optimal
      conditions of soaking temperature-pearling time were 73.3 C-4.8 min for red
      sorghum and 67.9 C-8.6 min for white sorghum, considering maximum endosperm yield
      and ash content lower than 0.65 g/100 g. In RF-PS obtained under optimal
      conditions, protein, lipid, Cu, and free polyphenols were higher in red sorghum
      than white sorghum (10.16 +/- 0.62 vs. 9.42 +/- 0.61 g/100 g, 0.89 +/- 0.16 vs.
      0.62 +/- 0.11 g/100 g, 2.08 +/- 0.21 vs. 1.88 +/- 0.20 mg/kg, 79.51 +/- 14.51 vs.
      63.82 +/- 4.33 mg/100 g). Fe, Zn, Ca, and Na were higher in white sorghum than
      red sorghum (20.61 +/- 2.92 vs. 17.56 +/- 0.98 mg/kg, 11.94 +/- 0.84 vs. 9.58 +/-
      1.65 mg/kg, 87.45 +/- 12.91 vs. 75.31 +/- 12.57 mg/kg, 129.62 +/- 9.03 vs. 102.69
      +/- 28.34 mg/kg). No difference was observed in the contents of ash, Mg, and K.
      It was possible to improve endosperm yield using a parboiling process prior to
      decortication. In addition, this process contributes to increase the mineral
      content in RF-PS.

PMID- 30111175
TI  - Evaluation of antibacterial and anti-biofilm properties of kojic acid against
      five food-related bacteria and related subcellular mechanisms of bacterial
      inactivation.
AB  - Although the antimicrobial properties of kojic acid have been recognized, the
      subcellular mechanism of bacterial inactivation caused by it has never been
      clearly elucidated. In the present study, the antibacterial and anti-biofilm
      activity of kojic acid was evaluated against five foodborne pathogens including
      Listeria monocytogenes, Bacillus subtilis, Staphylococcus aureus, Escherichia
      coli, and Salmonella typhimurium. The antibacterial activity was determined by
      minimum inhibitory concentration, minimum bactericidal concentration, and the
      time-kill assay. Among them, the susceptibility of Escherichia coli was
      significant with the lowest minimum inhibitory concentration and minimum
      bactericidal concentration values of 10 and 20 mM, respectively. Subcellular
      mechanism of bacterial inactivation related to kojic acid was revealed through
      comprehensive factors including cell morphology, membrane permeability, K+
      leakage, zeta potential, intracellular enzyme, and DNA assay. Results
      demonstrated that bacterial inactivation caused by kojic acid, especially for
      Gram-negative bacteria, was primarily induced by the pronounced damage to the
      cell membrane integrity. Leakage of intracellular enzyme to the supernatants
      implied that the cell membrane permeability was compromised. Consequently, the
      release of K+ from the cytosol leads to the alterations of the zeta potential of
      cells, which would disturb the subcellular localization of some proteins and
      thereby cause the bacterial inactivation. The free -CH2OH group at the C-2 of
      kojic acid could play more significant role in the antimicrobial performance of
      kojic acid against Gram-negative bacteria. Moreover, remarkable interaction with
      DNA was also observed. Kojic acid at sub-minimum inhibitory concentration
      inhibited biofilm formation by these bacteria.

PMID- 30111178
TI  - Lassa fever outbreaks in Nigeria.

PMID- 30111177
TI  - Application of high hydrostatic pressure on Pacific white shrimp ( Litopenaeus
      vannamei) pate: Microbiological, physicochemical and consumer acceptance.
AB  - The locally elaborated shrimp pate is highly susceptible to microbial spoilage
      and deterioration during storage due to its content in nutrients. These
      conditions limit its commercialization in a larger scale. High hydrostatic
      pressure is an alternative to heat treatments technology used to inactivate
      microorganisms. The aim of this project was to evaluate the effect of high
      hydrostatic pressure on quality parameters and microbiological stability of
      Pacific white shrimp ( Litopenaeus vannamei) pate during storage. Shrimp pate was
      pressurized to 400, 500 and 600 MPa for 90 and 180 s. Samples were analysed for
      physicochemical, microbiological and flavour profile up to 21 days of storage at
      4 C. A hedonic test was made to evaluate the acceptance of pate. No
      microorganisms were detected at 600 MPa for 180 s and a shelf life of 14 days was
      reached. No relevant changes in pH or colour of pressurized samples were
      detected; flavour profile did not show any changes after being pressurized or
      during storage. Shrimp pate treated with 600 MPa for 180 s presented good sensory
      acceptance. High hydrostatic pressure treatments could improve microbiological
      quality of shrimp pate without a sensible modification of the physicochemical and
      sensorial qualities of this product.

PMID- 30111179
TI  - Analysis and identification of symptoms and risk factors in a cohort of chronic
      hypertensive patients in a tertiary care hospital in Sri Lanka.
AB  - BACKGROUND: Hypertension (HT) is identified as a highly prevalent cardiovascular
      risk factor and also as a separate disease entity, leading to significant
      mortality and morbidity. The rate of HT is increasing worldwide with a faster
      rate identified in developing countries. Thus, it is important to evaluate
      epidemiological patterns of chronic HT in a developing country like Sri Lanka.
      METHODOLOGY: This is a cross-sectional descriptive study conducted at the
      Teaching Hospital Peradeniya, Sri Lanka, to assess symptoms and risk factors
      among patients with chronic HT. RESULTS: In a cohort of 266 chronic
      hypertensives, the mean values for age of population, age of onset, and duration
      of HT, respectively, are 63, 45, and 8 years. At presentation, 24.8% were
      asymptomatic. The commonest presentation at diagnosis was dizziness accounting
      for 33.8% cases, followed by chest pain, headache, loss of consciousness, and
      shortness of breath accounting for 7.5%, 13.5%, 2.6%, and 4.5%, respectively.
      Approximately 36.5% of patients had a positive family history. Fathers of 7.1%
      patients, mothers of 19.2%, and both parents of 10.2% patients had HT. 38.7% of
      patients had one or more siblings with HT. 34.6% had diabetes mellitus.
      CONCLUSION: Symptoms of those with HT are mostly nonspecific and should be
      considered as possible warning signs prior to the development of sinister
      complications of the disease. Family history of HT with affected siblings, or one
      of the parents, was, observed in more than one-third of patients. Early screening
      and prevention of modifiable risk factors are important in these patients to
      prevent debilitating complications.

PMID- 30111180
TI  - Co-creation of a family-focused service model living with younger onset dementia.
AB  - Families living with younger onset dementia face unique social challenges, which
      services do not currently address. There is a gap in understanding the
      experiences of families affected by younger onset dementia, including the
      interactions and relationships within the family units, and with existing
      services and supports. In this qualitative research study, semi-structured
      interviews were conducted across Australia with seven health and social care
      providers, five persons living with younger onset dementia, six spouse/carers,
      and 17 children. A thematic analysis was conducted using a theoretical lens drawn
      from the combined perspectives of the social model of disability and family
      systems-illness model. Two central themes emerged in the data: (1) Understanding
      the social demands on the family - lifecycle challenges living with younger onset
      dementia from a social and family context; and (2) Interactions of health and
      social care providers with families living with younger onset dementia -
      opportunities and challenges in providing support and services geared to a whole
      family approach. In order to provide families for those living with younger onset
      dementia with optimal assistance and support, co-creation of a family-focused
      services model is proposed. Its purpose is to support effective therapeutic
      interactions and service development among service users, service providers, and
      stakeholders.

PMID- 30111181
TI  - Patterns of antibody response during natural hRSV infection: insights for the
      development of new antibody-based therapies.
AB  - INTRODUCTION: The human respiratory syncytial virus (hRSV) is the main cause of
      acute lower respiratory tract infection in susceptible population worldwide, such
      as young children and the elderly. Although hRSV is a major public health burden,
      there are no licensed vaccines and the only available therapy is palivizumab.
      During life, reinfections with hRSV are common, suggesting that the virus can
      impair the development of an efficient host immune response. This feature has
      hindered the development of efficient therapies. Areas covered: This article
      focuses on research about the natural development of antibodies in humans after
      the exposure to hRSV. The difficulties of developing anti-hRSV therapies based on
      monoclonal antibodies have been recently associated to the relationship between
      the disease outcome and the pattern of antibody response. Expert opinion:
      Development of monoclonal antibodies is a potentially successful approach to
      prevent the population from suffering severe respiratory diseases caused by hRSV
      infection, for which there are no available vaccines. Although the use of
      palivizumab is safe, its effectiveness is controversial. Recent data have
      prompted research to develop therapies targeting alternative viral antigens,
      rather than focusing only on the F protein, as well as the development of
      antibodies with a cell-mediated function.

PMID- 30111182
TI  - Latest advances in diagnosing and predicting DILI: what was new in 2017?
AB  - INTRODUCTION: Drug-induced liver injury (DILI) remains an increasingly recognized
      cause of hepatotoxicity and liver failure worldwide. In 2017, we continued to
      learn about predicting, diagnosing, and prognosticating drug hepatotoxicity.
      Areas covered: In this review, we selected from over 1200 articles from 2017 to
      synopsize updates in DILI. There were new HLA haplotypes associated with
      medications including HLA-C0401 and HLA-B*14. There has been continued work with
      quantitative systems pharmacology, particularly with the DILIsym(r) initiative,
      which employs mathematical representations of DILI mechanisms to predict
      hepatotoxicity in simulated populations. Additionally, knowledge regarding
      microRNAs (miRNAs) continues to expand. Some new miRNAs this past year include
      miRNA-223 and miRNA-605. Aside from miRNAs, other biomarkers for diagnosis,
      prognosis, and even prediction of DILI were explored. Studies on K18, OPN, and
      MCSFR have correlated DILI and liver-associated death within 6 months.
      Conversely, a new prognostic panel using apolipoportein-A1 and haptoglobin has
      been proposed to predict recovery. Further study of CDH5 has also provided
      researchers a possible new biomarker for prediction and susceptibility to DILI.
      Expert commentary: Although research on DILI remains quite promising, there is
      yet to be a reliable, simple method to predict, diagnose, and risk assess this
      form of hepatotoxicity.

PMID- 30111183
TI  - Clinical and pharmacological profile of benznidazole for treatment of Chagas
      disease.
AB  - INTRODUCTION: Chagas disease (CD) is one of the most neglected public health
      problems in the Americas, where <1% of the estimated 6 million people with the
      infection have been diagnosed and treated. The goal of treatment is to eliminate
      the parasite, decrease the probability of cardiomyopathy and other complications
      during the chronic stage of infection, and interrupt the cycle of disease
      transmission by preventing congenital infection. Currently, only benznidazole
      (BZN) and nifurtimox are recognized by the World Health Organization as effective
      drugs for treatment of CD. In this paper, we provide an overview of the clinical
      pharmacology of BZN. Areas covered: This review covers the historical background,
      chemistry, mechanism of action, pharmacokinetics, preclinical research,
      resistance, clinical research, toxicology, adverse effects, and current
      regulatory status of BZN. Expert commentary: Ongoing investigations aim to
      optimize BZN therapy by adjusting the current standard regimen or by combining
      BZN with new chemical entities. These studies are assessing alternatives that
      improve safety while maintaining or increasing the efficacy of BZN. Timely
      diagnosis and antitrypanosomal treatment are critical components of programs to
      eliminate CD as a public health problem, and can dramatically reduce the heavy
      burden of morbidity and mortality caused by the disease.

PMID- 30111184
TI  - Association of Maternal Insecticide Levels With Autism in Offspring From a
      National Birth Cohort.
AB  - OBJECTIVE: Autism is a complex neurodevelopmental disorder with a largely unknown
      etiology. To date, few studies have investigated prenatal exposure to toxins and
      risk of autism by using maternal biomarkers of exposure. Persistent organic
      pollutants are lipophilic halogenated organic compounds and include the
      insecticide dichlorodiphenyltrichloroethane (DDT), as well as its metabolite p,p'
      dichlorodiphenyl dichloroethylene (p,p'-DDE), and polychlorinated biphenyls
      (PCBs). The objective of this study was to test whether elevated maternal levels
      of persistent organic pollutants are associated with autism among offspring.
      METHOD: The investigation was derived from the Finnish Prenatal Study of Autism,
      a national birth cohort study based on a nested case-control design. Cases of
      autism among children born between 1987 and 2005 were ascertained by national
      registry linkages. In cases of childhood autism and matched control subjects (778
      matched case-control pairs), maternal serum specimens from early pregnancy were
      assayed for levels of p,p'-DDE and total levels of PCBs. RESULTS: The odds of
      autism among offspring were significantly increased with maternal p,p'-DDE levels
      that were in the highest 75th percentile, with adjustment for maternal age,
      parity, and history of psychiatric disorders (odds ratio=1.32, 95% CI=1.02,
      1.71). The odds of autism with intellectual disability were increased by greater
      than twofold with maternal p,p'-DDE levels above this threshold (odds ratio=2.21,
      95% CI=1.32, 3.69). There was no association between total levels of maternal
      PCBs and autism. CONCLUSIONS: These findings provide the first biomarker-based
      evidence that maternal exposure to insecticides is associated with autism among
      offspring. Although further research is necessary to replicate this finding, this
      study has implications for the prevention of autism and may provide a better
      understanding of its pathogenesis.

PMID- 30111186
TI  - Risk of Major Malformations in Infants Following First-Trimester Exposure to
      Quetiapine.
AB  - OBJECTIVE: Second-generation antipsychotics are commonly prescribed to
      reproductive-age women for the treatment of a spectrum of psychiatric disorders.
      Quetiapine is the most commonly prescribed medication in this class, and
      therefore a better understanding of its reproductive safety profile is critical.
      The goal of this study was to determine the risk of major malformations among
      infants exposed to quetiapine during pregnancy compared with a group of infants
      whose mothers had a history of psychiatric morbidity but who did not use a second
      generation antipsychotic during pregnancy. METHOD: The National Pregnancy
      Registry for Atypical Antipsychotics interviews pregnant women ages 18-45 during
      pregnancy and the postpartum period. Obstetric, labor, and delivery medical
      records and pediatric medical records from the first 6 months of life were
      screened for evidence of major malformations, followed by adjudication by a
      blinded dysmorphologist. Women with first-trimester exposure to quetiapine were
      compared with control subjects without exposure to second-generation
      antipsychotics. RESULTS: As of March 2017, 888 women had enrolled prospectively
      and 357 were eligible for analysis. Of these, 152 women with first-trimester
      exposure to quetiapine were compared with 205 control subjects without any second
      generation antipsychotic exposure. For the 155 infants born to women in the
      exposed group (including three sets of twins), two major malformations were
      confirmed (1.3%), compared with three major malformations among the 210 infants
      born in the unexposed group (including five sets of twins) (1.4%). The unadjusted
      odds ratio for major malformations between infants with and without quetiapine
      exposure was 0.90 (95% CI=0.15, 5.46), which is consistent with the pooled
      estimate of the available controlled data on fetal exposure to quetiapine.
      CONCLUSIONS: These data regarding the safety of fetal exposure to quetiapine in a
      small sample of well-characterized participants are reassuring given that the
      confidence interval does not exceed a fivefold increased risk of major
      malformations relative to psychiatric control subjects. Future analyses based on
      ongoing data collection will produce more precise estimates.

PMID- 30111188
TI  - Profile of the Dutch committee for war prophylaxis.

PMID- 30111185
TI  - Early Variations in White Matter Microstructure and Depression Outcome in
      Adolescents With Subthreshold Depression.
AB  - OBJECTIVE: White matter microstructure alterations have recently been associated
      with depressive episodes during adolescence, but it is unknown whether they
      predate depression. The authors investigated whether subthreshold depression in
      adolescence is associated with white matter microstructure variations and whether
      they relate to depression outcome. METHOD: Adolescents with subthreshold
      depression (N=96) and healthy control subjects (N=336) drawn from a community
      based cohort were compared using diffusion tensor imaging and whole brain tract
      based spatial statistics (TBSS) at age 14 to assess white matter microstructure.
      They were followed up at age 16 to assess depression. Probabilistic tractography
      was used to reconstruct white matter streamlines spreading from the regions
      identified in the TBSS analysis and along bundles implicated in emotion
      regulation, the uncinate fasciculus and the cingulum. The authors searched for
      mediating effects of white matter microstructure on the relationship between
      baseline subthreshold depression and depression at follow-up, and then explored
      the specificity of the findings. RESULTS: Lower fractional anisotropy (FA) and
      higher radial diffusivity were found in the anterior corpus callosum in the
      adolescents with subthreshold depression. Tractography analysis showed that they
      also had lower FA in the right cingulum streamlines, along with lower FA and
      higher mean diffusivity in tracts connecting the corpus callosum to the anterior
      cingulate cortex. The relation between subthreshold depression at baseline and
      depression at follow-up was mediated by FA values in the latter tracts, and lower
      FA values in those tracts distinctively predicted higher individual risk for
      depression. CONCLUSIONS: Early FA variations in tracts projecting from the corpus
      callosum to the anterior cingulate cortex may denote a higher risk of transition
      to depression in adolescents.

PMID- 30111187
TI  - Discoveries on the Genetics of ADHD in the 21st Century: New Findings and Their
      Implications.
AB  - The 21st century has witnessed the discovery of multiple rare and common gene
      variants associated with attention deficit hyperactivity disorder (ADHD), and
      these discoveries have already provided a starting point for the investigation of
      the biology of the disorder and novel treatments. The purpose of this selective
      review is to examine genetic findings from the past 5 years and consider their
      implications for the conceptualization of ADHD and future clinical practice.
      Recent discoveries reveal the strong genetic overlaps between ADHD and autism
      spectrum disorder (ASD) as well as intellectual disability. Thus, the removal of
      the previous diagnostic exclusion criteria for ADHD in the presence of ASD is a
      welcome change in DSM-5. However, ADHD also shows substantial genetic
      correlations with a much broader group of neuropsychiatric disorders as well as
      with nonpsychiatric conditions (e.g., lung cancer). Investigating potential
      explanations for these links is an important next step. ADHD, while usefully
      conceptualized as a disorder in clinical practice, can be viewed as a trait.
      Recent genome-wide association study findings, consistent with twin studies,
      highlight that ADHD lies at the extreme end of a continuously distributed
      dimension, akin to hypertension along the continuum of blood pressure. Although
      ADHD levels typically decline with age, twin and molecular genetic studies
      suggest that a persistent trajectory is associated with higher genetic loading.
      Routine testing for rare mutations in ADHD is not yet recommended, although
      guidelines in many countries recommend testing individuals with mild intellectual
      disability or ASD, so practice could change. Common gene variants for ADHD are
      only weakly predictive and therefore have limited clinical value at present, as
      does pharmacogenomics. [AJP at 175: Remembering Our Past As We Envision Our
      Future November 1938: Electroencephalographic Analyses of Behavior Problem
      Children The electroencephalogram was the first biological technique to be
      applied to childhood behavioral disorders. Jasper, Solomon, and Bradley reported
      that "the electroencephalogram has succeeded in revealing a definite abnormality
      of brain function in over one half of a group of childhood behavior disorders
      which had been previously considered as largely psychogenic." (Am J Psychiatry
      1938; 95:641-658 )].

PMID- 30111190
TI  - A Review of the Hepatitis B Foundation Website.
AB  - The hepatitis B virus (HBV) is a preventable infection that can lead to chronic
      HBV and liver cancer without timely detection and treatment. The Hepatitis B
      Foundation is a national organization that helps coordinate local coalitions that
      work at the community level. The Hepatitis B Foundation website (
      http://www.hepb.org/ ) serves as an interactive, educational website for
      patients, informal caregivers (e.g., family members), physicians, and community
      stakeholders such as local/regional health organizations and community
      coalitions. The multifaceted site provides user-friendly resources and tools that
      are available in several different languages to reach the global HBV patient
      population. Topic-delimited tabs (i.e., "What Is Hepatitis B?," "Prevention &
      Diagnosis," "Treatment & Management," "Resources & Support," "Research &
      Programs," and "News & Events") keep web content organized and easy to browse.
      The website also provides interactive tools such as blogs and social media
      campaigns that support peer-to-peer engagement. Additionally, the website
      stresses the importance of HBV prevention using resources on primary, secondary,
      and tertiary prevention. Overall, the website is a very useful tool for anyone
      seeking more information on topics related to HBV prevention, diagnosis, and
      treatment.

PMID- 30111191
TI  - Craniofacial venous malformations treated by percutaneous sclerotherapy using
      polidocanol: a single-center experience.
AB  - Background Percutaneous therapy with various sclerosants is an established
      treatment of venous malformations in general. We investigated the safety and
      effectiveness of polidocanol in the craniofacial region. Purpose To present and
      evaluate our subjective and objective mid- and long-term results of patients with
      craniofacial venous malformations (CFVM) after percutaneous sclerotherapy using
      polidocanol. Material and Methods Twenty patients with CFVM treated by
      percutaneous sclerotherapy were followed up and asked to fill in a questionnaire
      comparing levels of the following CFVM-related symptoms before and after
      treatment: pain; functional impairment; cosmetic deformities; and impairment in
      daily life. Additionally, both size reduction as well as procedural-related
      complication rates were analyzed. Results Evaluation of the questionnaire
      revealed an improvement or complete relief of CFVM-related symptoms with
      significant reduced impairment in daily life after percutaneous sclerotherapy.
      Eighteen (90%) patients noticed a post-sclerotherapy improvement of at least one
      of their corresponding symptoms and expressed satisfaction with regard to their
      treatment. For 13 patients, a > 50% size reduction of the CFVM could be observed,
      while seven exhibited a < 50% size reduction. One minor complication was
      encountered in 56 treatment sessions (1.8%). Conclusion Percutaneous
      sclerotherapy using polidocanol is a well-tolerated treatment for CFVM with a low
      complication rate. Size reduction and positive results with improvement of
      different clinical symptoms can be achieved.

PMID- 30111192
TI  - The relationship between rotator cuff tear and four acromion types: cross
      sectional study based on shoulder magnetic resonance imaging in 227 patients.
AB  - Background Rotator cuff tear (RCT) has been believed to be related to specific
      types of the acromion. However, most of the studies were performed on a small
      number of patients with surgical findings not considering the severity of RCT.
      Purpose To analyze the relationship between age, gender, the side of the
      shoulder, the acromion type, and the severity of RCT using shoulder magnetic
      resonance arthrography (MRA). Material and Methods A total of 277 shoulder MRA
      findings were analyzed by a radiologist specializing in the musculoskeletal
      system. The relationship between variables (age, gender, side of the shoulder,
      and acromion type) and the injury of the supraspinatus (no rupture, partial
      rupture, full rupture, complete rupture) was confirmed. The partial tear of the
      supraspinatus tendon was divided into bursal and articular side tear in order to
      investigate the damage caused by the anatomical difference of the acromion. We
      also confirmed the differences between single supraspinatus injury and multiple
      RCTs. Results The severity of supraspinatus tear and multiple RCTs were
      statistically significant with the old age and the right side of the shoulder,
      but not with a specific acromion type. In supraspinatus partial tear, there was
      no statistical difference between bursal and articular side tears. Conclusion Our
      study revealed that the age at which degeneration could occur also was associated
      with multiple RCTs and is considered to be the most important factor in RCT, not
      anatomical structures such as acromion type.

PMID- 30111194
TI  - The 100 top-cited articles focused on magnetic resonance: a bibliometric
      analysis.
AB  - Background The number of citations that an article has received can be used to
      evaluate its impact on a particular research area. Purpose The aim of this study
      was to identify and characterize the 100 top-cited articles focused on magnetic
      resonance (MR). Material and Methods We determined the 100 top-cited articles on
      MR via the Scopus database, using the search term. The following information was
      recorded for each article: year of publication; journal title; impact factor of
      journal; number of citations; number of annual citations; authorship; department;
      institution; country; type of article; topic; MR protocol; and disease. Results
      The number of citations for the 100 top-cited articles was in the range of 898
      5679 (median = 1342.5) and the number of annual citations was in the range of
      19.7-372.4 (median = 60.9). The 100 top-cited articles were published in 46
      journals, led by Magnetic Resonance in Medicine (n = 13). The majority of
      articles were published in 1990-1999 (n = 53), originated in the United States (n
      = 69), were original articles (n = 81), and dealt with the clinical application
      of MR (n = 57). The Department of Radiology, Massachusetts General Hospital (n =
      5) was the leading institution. The majority of articles did not use any specific
      protocol (n = 51) and was not associated with any specific disease (n = 56).
      Conclusion Our study presents a detailed list and analysis of the 100 top-cited
      articles on MR, which provides an insight into historical development in this
      field.

PMID- 30111193
TI  - 18F FDG-PET/CT evaluation of histological response after neoadjuvant treatment in
      patients with cancer of the esophagus or gastroesophageal junction.
AB  - Background In most parts of the world, curatively intended treatment for
      esophageal cancer includes neoadjuvant therapy, either with chemoradiotherapy or
      chemotherapy alone, followed by esophagectomy. Currently 18F-FDG positron
      emission tomography/computed tomography (PET/CT) is used for preoperative disease
      staging, but is not well established in the evaluation of neoadjuvant treatment.
      Purpose To evaluate changes in PET parameters in relation to the histological
      primary tumor response in the surgical specimen in patients randomized to
      neoadjuvant chemoradiotherapy or chemotherapy. Material and Methods Patients were
      randomized between either neoadjuvant chemotherapy or chemoradiotherapy followed
      by esophagectomy.18F-FDG PET/CT exams were conducted at baseline and following
      neoadjuvant treatment. Standardized uptake ratio (SUR) values were measured in
      the primary tumor and compared as regards histological responders and non
      responders as well as different treatment arms. Results Seventy-nine patients
      were enrolled and 51 were available for analysis. A significant rate of SUR
      reduction was observed ( P = 0.02) in the primary tumor in histological
      responders compared to non-responders. Changes in SUR were significantly greater
      in responders following chemoradiotherapy ( P = 0.02), but not following
      chemotherapy alone ( P = 0.49). There was no statistically significant difference
      in SUR in patients with a complete histological response compared to those with a
      subtotal response. Conclusion Our results are similar to those of previous
      studies and show that changes in the rate of SUR can be used reliably to
      differentiate histological responders from non-responders after neoadjuvant
      treatment with either chemoradiotherapy or chemotherapy. Limitations of current
      PET technology are likely to restrict the possibility of accurately ruling out
      limited residual disease.

PMID- 30111196
TI  - Tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia.
AB  - INTRODUCTION: Cure rates for pediatric and young adult patients with refractory
      or recurrently relapsed acute lymphoblastic leukemia (ALL) are dismal. Survival
      from time of relapse is typically measured in weeks to months, and standard
      chemotherapy and currently approved targeted therapy achieve remission in less
      than a third of affected patients. To date, the only definitive curative therapy
      has been allogeneic hematopoietic stem cell transplant (HSCT). Advances in
      immunotherapy, with the introduction of chimeric antigen receptor T-cell
      therapies and the development of tisagenlecleucel, have changed the landscape.
      Areas covered: This review will describe the pharmacology of tisagenlecleucel and
      summarize the clinical evidence for its use in the treatment of multiple-relapsed
      or refractory B-cell ALL (B-ALL). Also discussed are other immunotherapies for B
      ALL as well as the most commonly-encountered toxicities and corresponding
      management strategies. Expert commentary: Early phase trials indicate that
      tisagenlecleucel significantly improves survival for patients with B-ALL that is
      refractory or in second or later relapse. In responding patients, remissions have
      been reported on the order of years, and thus, tisagenlecleucel may herald a
      dramatic shift in the treatment paradigm of this largely fatal disease.

PMID- 30111195
TI  - Outcomes of percutaneous transluminal biopsy of biliary lesions using a dedicated
      forceps system.
AB  - Background Distinction between benign and malignant biliary obstruction is always
      challenging. Purpose To evaluate outcomes of percutaneous transluminal biopsy of
      biliary strictures using a dedicated forceps system. Material and Methods This
      prospective, single-center, single-arm study, included 29 consecutive patients
      (17 men [56.6%]; mean age = 60 +/- 9 years), who underwent 30 transluminal
      biopsies during percutaneous transhepatic biliary drainage (PTBD) due to
      obstructive jaundice, between September 2014 and January 2017, using a
      transluminal biliary access and biopsy forceps set. The study's primary efficacy
      endpoint was technical success and the primary safety endpoint was the procedure
      related major complications rate. The study's secondary endpoints were procedure
      related minor complication rate, sensitivity, specificity, and diagnostic
      accuracy for the characterization of malignancy. Results Tissue samples allowed
      histological diagnosis in 27/30 procedures (technical success rate 90.0%), as in
      three cases (10.0%) the sample was characterized as non-diagnostic: one case was
      suspicious for pancreatic cancer and two cases were cholangiocarcinoma. In one
      case, biopsy was successfully repeated. The diagnosis was cholangiocarcinoma in
      16 cases (53.3%), colorectal metastasis in three cases (10%), pancreatic
      adenocarcinoma in three cases (10.0%), and inflammation in five cases (16.6%).
      There were two false-negative cases of inflammation proven to be
      cholangiocarcinoma, resulting in sensitivity of 91.67%, specificity of 100%, and
      accuracy of 92.59%. No major complications were noted. There were four cases of
      hemobilia (13%) which auto-resolved within 48 h. Conclusion Percutaneous
      transluminal biopsy of biliary strictures during PTBD using the specific forceps
      system was proven safe and resulted in high technical success and diagnostic
      accuracy rates.

PMID- 30111197
TI  - Predictors of Posttraumatic Growth Among University Students Who Experienced a
      Recent Earthquake.
AB  - A 5.8 magnitude earthquake hit Gyeongju City, South Korea, in 2016, traumatising
      and psychologically panicking residents. The purpose of this study was to
      identify predictive factors for posttraumatic growth (PTG) among university
      students who experienced South Korea's largest earthquake. A cross-sectional
      descriptive survey was distributed to a convenience sample of 493 university
      students in Gyeongju City. Data were collected via 5 self-report questionnaires.
      PTG was found to be positively correlated with posttraumatic stress disorder
      (PTSD), resilience and social support. Multiple regression analysis showed that
      PTSD (beta = 0.519, p < .001), resilience (beta = 0.213, p < .001), religion
      (beta = 0.125, p = .001) and sex (female; beta = 0.090, p = .010) were identified
      as predictive factors of PTG. These results illustrate a need for health care
      providers to include individual internal resources such as resilience in
      intervention strategies to promote PTG and decrease posttraumatic experiences in
      those who have experienced traumatic events such as earthquakes. A longitudinal
      study is needed to obtain more definitive evidence of PTSD progression and PTG
      over time.

PMID- 30111198
TI  - Curcumin as a therapeutic agent for blocking NF-kappaB activation in ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic, relapsing, remitting, and inflammatory
      disorder that afflicts millions of people around the world. It carries a
      substantial economic burden, reducing the quality of life, ability to work, and
      increasing disability. Conventional medical treatment of UC includes the use of
      aminosalicylates, corticosteroids, and immunosuppressive drugs. However, these
      medicines are not always effective due to some serious side effects. Nuclear
      factor-kappa B (NF-kappaB) is a key factor in the inflammatory setting and
      strongly affects the course of mucosal inflammation in UC. This review aims to
      describe the complex role of NF-kappaB in UC and discuss existing pharmacological
      attempts by curcumin for blocking NF-kappaB activation to develop new therapeutic
      strategies in UC. Several studies have shown intriguing pharmacologic effects
      associated with curcumin, which inhibits NF-kappaB expression by regulating NF
      kappaB/IkB pathway and down-regulation expression of pro-inflammatory cytokines,
      such as Interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha.
      The efficacy of curcumin has been confirmed in several experimental models of UC.
      Furthermore, curcumin significantly induced clinical remission in active mild-to
      moderate UC patients and reduced clinical relapse in quiescent UC patients. The
      inhibitory effects of curcumin on NF-kappaB and its unrivaled safety profile
      indicate that it remains effective for the treatment of UC. In addition, curcumin
      is a nontoxic, inexpensive, and easily available natural polyphenol. In
      conclusion, curcumin can be used as a potential and safe drug in the management
      of patients with remission and mild-to-moderate UC.

PMID- 30111200
TI  - Valproate for Schizophrenia.

PMID- 30111199
TI  - Acoustic signal of silent tracheal aspiration in children with oropharyngeal
      dysphagia.
AB  - : Objetive: The aim of this study was to characterize the acoustic signal of
      silent tracheal aspiration in children with oropharyngeal dysphagia (OPD).
      METHOD: Thirty-two children with OPD were examined with combined digital cervical
      auscultation (DCA) and videofluoroscopic swallow study (VFSS). Power spectral
      density (PSD, in 1/?Hz) of the acoustic signal from a sequential series of five
      liquid swallows was used for comparisons between children who silently aspirated
      and children who did not aspirate on VFSS. Fourteen children were excluded due to
      either DCA/VFSS artifact or non-silent aspiration (cough, choking). RESULTS: The
      remaining 18 participants (median age 6 years, range 2-12.8) were classified
      based on VFSS as aspirators (n = 8) and non-aspirators (n = 10). The PSD curve of
      aspirators presented an ascending pattern (1st vs. 5th deglutition: 695.2 vs.
      4421.9 1/?Hz), while the curve of non-aspirators was flat (1st vs. 5th
      deglutition: 509 vs. 463.4 1/?Hz), with marked differences being observed from
      the 3rd measure onwards (p < .001). In this study, DCA was able to identify
      silent tracheal aspiration in children with OPD. CONCLUSION: This non-invasive
      technique identified aspiration by an increase in the PSD curve in aspiration
      sounds.

PMID- 30111201
TI  - A Pilot Study Exploring Nursing Knowledge of Depression and Suicidal Ideation in
      Kenya.
AB  - Nurses play key roles in recognizing, diagnosing, managing, and referring persons
      with mental disorders. This cross-sectional study assessed mental health literacy
      (depression and suicidal ideation) among nurses in a private urban referral
      hospital in Kenya. Nurses read a vignette and answered questions regarding
      diagnosis, treatment/interventions, and related attitudes and beliefs. Thirty
      seven nurses (12 males) completed the questionnaire. Three correctly identified
      the diagnosis and 23 identified depression only. Although 75% noted the symptoms
      were extremely distressing, fear, and stigma were common reactions. This
      highlights challenges in mental health promotion/prevention in Kenya, and
      suggests continuous nursing education and curriculum enhancement is needed.

PMID- 30111203
TI  - Self-Reported Needs for Care, Support and Treatment of Persons Who Frequently
      Visit Psychiatric Emergency Rooms in Sweden.
AB  - AIM: To investigate self-reported needs for care, support and treatment among
      persons who frequently visit psychiatric emergency rooms (PERs). DESIGN: A cross
      sectional design. Qualitative and quantitative data were collected using an
      interview-based manual. Qualitative data were analysed using content analysis,
      whereas quantitative data were analysed using descriptive, non-parametric
      statistical tests. RESULTS: Persons who frequently visit PERs self-reported unmet
      needs for care, support and treatment in life domains such as health,
      socialisation, daytime activities, and emotional and financial security.
      CONCLUSION: To meet the needs of persons who frequently visit PERs, close
      cooperation between concerned welfare actors should be implemented.

PMID- 30111202
TI  - Effect of characteristics and life in cities in China on residents' smoking
      behaviour.
AB  - Objective This study aimed to identify the relationship between city-level
      economic development and smoking behaviour. Methods Using multilevel mixed
      effects logistic methods, we examined the relationship between smoking/passive
      smoking and respondents' lifestyles in the city. Results We found that
      respondents living in cities with higher per capita gross domestic product (GDP)
      were less likely to smoke than those living in cities with lower per capita GDP
      (odds ratio [OR] = 0.977, 95% confidence interval [CI]: 0.958-0.997). Further,
      respondents with higher levels of life satisfaction and subjective social status
      were less likely to smoke than those with lower levels of these variables (OR =
      0.942, 95% CI: 0.893-0.994; OR = 0.955, 95% CI: 0.928-0.983, respectively). In
      terms of passive smoking, respondents with higher levels of subjective social
      status in their cities were less likely to smoke than those with lower levels (OR
      = 0.972, 95% CI: 0.948-0.996). Smoking and exposure to second-hand smoke were
      more common among those with lower socioeconomic status. Conclusions Smoking is
      one of the most serious public health hazards in China. People's smoking
      behaviour is significantly related to characteristics of their cities and their
      socioeconomic status. Improved smoking-prevention measures are urgently required
      in China.

PMID- 30111204
TI  - Therapeutic Intervention of Aloe Gel Containing Nano-Sized and Micron-Sized
      Silver Sulfadiazine Gel on Second-Degree Burn: A Comparative Study.
AB  - The current work focuses on the formulation development, optimization, and in
      vivo assessment of nano-sized silver sulfadiazine ( nSSD) and micron-sized silver
      sulfadiazine ( mSSD) topical gel composed of Aloe vera gel ( Aloe gel) and
      Carbopol 940 for the management of second-degree burn wound. The optimized
      concentration of gel-forming agent (Carbopol 940) was chosen based on best
      possible consistency and spreadability of the gel. The second-degree burn
      infliction was developed in the posterior region of rats followed by anesthesia.
      Afterward, the created wounds were further treated individually by both the gel
      formulation (1 application daily) for 14 days and observations were recorded. The
      nSSD gel showed better wound healing and a higher degree of tissue hyperplasia as
      compared with mSSD gel in rats. In vitro drug release study showed better drug
      release from nSSD gel (74.25 +/- 3.331%) as compared with mSSD gel formulation
      (61.32 +/- 2.112%) after 24 hours. The nSSD and mSSD topical gel-treated rats
      showed 95.63% and 78.75% wound healing after 14 days, while in the case of
      control group rats, 48.65% wound contraction was seen after 14 days. Furthermore,
      the histopathological study revealed that the nSSD gel was more efficient in
      controlling the wound infection and showed better wound healing as compared with
      mSSD gel formulation.

PMID- 30111205
TI  - Ketamine delays progression of oxidative and damaged cataract through regulating
      HMGB-1/NF-kappaB in lens epithelial cells.
AB  - OBJECTIVE: Lens epithelial cell (LEC) membrane damage is one of the pathogenesis
      of cataract. High mobility group box-1 (HMGB-1) and nuclear factor-kappaB (NF
      kappaB) play vital roles in a variety of diseases, such as inflammation. Ketamine
      has numerous pharmacological effects that can inhibit inflammation. However, its
      role in cataract rats LECs has not yet been elucidated. MATERIALS AND METHODS:
      LECs were isolated from SD rats and cultured in vitro. The cells were randomly
      divided into three groups, including the control group, cataract model group
      induced by H2O2, and ketamine group treated by 10 mM ketamine under H2O2
      environment. LECs proliferation was assessed by MTT assay. LECs apoptosis was
      evaluated by Caspase-3 activity detection. NF-kappaB mRNA and protein expressions
      were tested by real-time PCR and Western blot. HMGB-1 expressions in cells and
      supernatant were detected by real-time PCR and ELISA. TNF-alpha and IL-1beta
      secretions were detected by ELISA. RESULTS: In H2O2 model group, the LECs
      proliferation was significantly inhibited, the caspase-3 activity significantly
      increased, HMGB-1 mRNA and secretion significantly enhanced, NF-kappaB mRNA and
      protein levels significantly elevated, compared to the Control group (p < .05).
      While the TNF-alpha and IL-1beta secretions significantly up-regulated in H2O2
      model group compared to the Control group (p < .05). Ketamine significantly
      promoted the LECs proliferation, significantly reduced the caspase-3 activity,
      and significantly declined the HMGB expression compared to H2O2 model group (p <
      .05). The NF-kappaB mRNA and protein levels were significantly decreased, TNF
      alpha and IL-1beta secretions were significantly decreased in the Ketamine group
      compared with the model group (p < .05). CONCLUSIONS: Ketamine delays the
      progression of oxidative and damaged cataract by regulating HMGB-1/NF-kappaB
      expression, inhibiting TNF-alpha, IL-1beta, and apoptosis, and promoting cell
      proliferation.

PMID- 30111207
TI  - Modification and Initial Psychometric Evaluation of the Physical Health Attitude
      Scale for Use in the Canadian Mental Health and Addictions Context.
AB  - INTRODUCTION: The Physical Health Attitude Scale (PHASe) tool was developed to
      better understand mental health nurses' attitudes towards their involvement and
      confidence in physical health care. This tool has been used in the United Kingdom
      and Australia; however, it has not been used in Canada. AIM: This study aims to
      modify and provide an initial psychometric evaluation of the PHASe tool for use
      in a Canadian mental health and addictions context. METHODS: In Phase 1, clinical
      experts (n = 8) were consulted to provide feedback on the content and face
      validity of the PHASe tool. In Phase 2, the PHASe tool was piloted with nurses at
      a large urban mental health and addiction organization in Ontario, Canada (n =
      77). RESULTS: In Phase 1, 4 items were added and 5 items were removed from the
      tool based on feedback provided by experts. In Phase 2, 12 poorly correlated
      items were removed. A two-factor solution was identified, with subscales
      "confidence" and "barriers and attitudes". DISCUSSION: Initial psychometric
      evaluation suggests that a revised 15-item version of the PHASe tool is valid and
      reliable in a Canadian mental health and addictions context; however, more
      testing is recommended in larger, more diverse samples.

PMID- 30111206
TI  - Comatose patient with hypothermia, dyspnea, and general edema in the emergency
      department: a case report.
AB  - Patients presenting to the emergency department with hypothermia are rare and
      often require prompt diagnosis and management. Myxedema coma, which may cause
      severe hypothermia, is a true endocrine emergency requiring early and appropriate
      treatment. We report on a 47-year-old woman with a history of hyperthyroidism who
      underwent thyroidectomy 5 years previously, with no regular medication or
      examinations. She presented to the emergency department with a 1-month history of
      progressive dyspnea associated with general weakness. She also showed
      hypothermia, decreased mental status, and general edema. Echocardiography
      revealed increased pericardial effusion without tamponade. Laboratory examination
      suggested myxedema coma and hypothyroidism. She received thyroxine,
      glucocorticoid supplement, and intensive supportive care, after which she
      gradually improved and was discharged. This case suggests that myxedema coma
      should be considered in patients with hypothyroidism or a history of
      thyroidectomy who present with change in consciousness, hypothermia, or other
      symptoms related to critical or slow presentation in multiple organs. Moreover,
      long-standing hypothyroidism or precipitating acute events such as sepsis,
      cerebrovascular accidents, gastrointestinal bleeding, cold exposure, trauma, and
      some medications may also cause myxedema coma. Myxedema coma is associated with a
      high mortality, and patients suspected to be suffering from this condition should
      be treated without delay.

PMID- 30111209
TI  - Clinical Validation of the Portuguese Version of "Substance Addiction
      Consequences" Derived from the Nursing Outcomes Classification.
AB  - Our aim was to contribute to the clinical validation of "Substance Addiction
      Consequences" (SAC) derived from the nursing outcomes classification (NOC), and
      to analyse psychometric properties. To that purpose, we applied a methodological
      design. The study's outcome comprises 16 nursing-sensitive indicators, within
      four different consequence factors: psychological and family; physical and
      cognitive ability; self-care; economic and work. The psychometric properties were
      considered good. We concluded that the scale can be used as a valid tool to
      measure the consequences of substance addiction and to assess the health status
      as a nursing sensitive outcome. The scale is considered valid to monitor nursing
      interventions in the clinical setting; being a comprehensive tool it allows the
      nurse to understand better this complex health problem.

PMID- 30111208
TI  - Intraductal papillary neoplasm of the bile duct: a single-center retrospective
      study.
AB  - Objective Intraductal papillary neoplasm of the bile duct (IPNB) has been
      increasingly recognized and reported. However, its clinical features are still
      controversial because of its low incidence. In the present study, we investigated
      the characteristics of IPNB. Methods In total, 28 patients with IPNB were treated
      at our institution from January 2000 to December 2016. Clinical data were
      collected and a retrospective accurate database was constructed. Demographic
      characteristics, perioperative management, and prognosis were retrospectively
      analyzed. Results Abdominal discomfort was the most common symptom. Preoperative
      imaging revealed biliary tract dilatation in 23 patients. Left lateral or left
      hepatic lobectomy was the most frequently performed surgical procedure.
      Histological analysis revealed malignancy in 17 patients. Eighty-eight lymph
      nodes were swept from the patients with malignant disease, but only three were
      metastatic. Twenty-one patients were followed up for 3 to 60 months (mean, 29.4
      +/- 18.2 months). Seven patients died during the follow-up period. Patients with
      benign tumors had significantly greater disease-free survival. Conclusions IPNB
      is a rare biliary disease that occurs mainly in patients of advanced age. The
      most common symptom is abdominal discomfort. Lymphatic metastasis is uncommon.
      Patients with benign tumors may have a better prognosis than those with malignant
      tumors.

PMID- 30111210
TI  - Characteristics, Prehospital Management, and Outcomes in Patients Assessed for
      Hypoglycemia: Repeat Access to Prehospital or Emergency Care.
AB  - BACKGROUND: In Ontario, Canada, there currently are no prehospital treat-and
      release protocols and the safety of this practice remains unclear. We sought to
      describe the characteristics, management, and outcomes of patients with
      hypoglycemia treated by paramedics, and to determine the predictors of repeat
      access to prehospital or emergency department (ED) care within 72 hours of
      initial paramedic assessment. METHODS: We performed a health record review of
      paramedic call reports and ED records over a 12-month period. We queried
      prehospital databases to identify cases, which included all adult patients (>= 18
      years) with a prehospital glucose reading of <72mg/dl (4.0mmol/L) and excluded
      terminally ill and cardiac arrest patients. We developed and piloted a
      standardized data collection tool and obtained consensus on all data definitions
      before initiation of data extraction by trained investigators. Data analyses
      include descriptive statistics with standard deviations, Chi-square, t-tests, and
      logistic regression with adjusted odds ratios (AdjOR). RESULTS: There were 791
      patients with the following characteristics: mean age 56.2, male 52.3%, known
      diabetic 61.6%, on insulin 46.1%, mean initial glucose 50.0 dl/mg (2.8 mmol/L),
      from home 56.3%. They were treated by an Advanced Care Paramedic 80.1%, received
      IV D50W 38.0%, IM glucagon 18.3%, PO complex carbs 26.6%, and accepted transport
      to hospital 69.4%. Of those transported, 134/556 (24.3%) were admitted and 9
      (1.6%) died in the ED. Overall, 43 patients (5.4%) had repeat access to
      prehospital/ED care, among those, 8 (18.6%) were related to hypoglycemia.
      Patients on insulin were less likely to have repeat access to prehospital/ED care
      (AdjOR 0.4; 95%CI 0.2-0.9). This was not impacted by initial (or refusal of)
      transport (AdjOR 1.1; 95%CI 0.5-2.4). CONCLUSION: Although risk of repeat access
      to prehospital/ED care for patients with hypoglycemia exists, it was less common
      among patients taking insulin and was not predicted by an initial refusal of
      transport.

PMID- 30111211
TI  - Prenatal and Postnatal Attachment Among Turkish Mothers Diagnosed with a Mental
      Health Disorder.
AB  - The presence of a mental disorder in the mother is one of the key factors
      affecting attachment. The present study aimed to evaluate prenatal and postnatal
      attachment among mothers diagnosed with a mental health disorder by comparing
      them to a healthy group. The patient group included women who received follow-up
      care in a psychiatric clinic (74 pregnant and 75 postpartum), and the healthy
      group consisted of women who attended a follow-up polyclinic (118 pregnant and 82
      postpartum). Data were collected using questionnaire forms, including the
      Prenatal Attachment Inventory and the Maternal Attachment Scale. Mothers
      diagnosed with a mental health disorder were determined to have lower attachment
      scores than the healthy group, both during the prenatal and postnatal periods.
      The literature suggests that mothers diagnosed with a mental health disorder
      showed low maternal attachment scores during pregnancy and/or the postnatal
      period. Psychiatric nurses should be involved in initiatives that may increase
      the prenatal and maternal attachment.

PMID- 30111213
TI  - The Effect of Music on Auditory Hallucination and Quality of Life in
      Schizophrenic Patients: A Randomised Controlled Trial.
AB  - The study was conducted to determine the effects of music on auditory
      hallucination and quality of life in schizophrenic patients. The sample of this
      randomised controlled study consisted of 28 patients (14 experimental and 14
      control groups) hospitalised with a diagnosis of schizophrenia (DSM-IV) and
      auditory hallucination. The study data were collected with the Information Form,
      The Scale for the Assessment of Positive Symptoms (SAPS), Characteristics of
      Auditory Hallucinations Questionnaire, and The World Health Organization Quality
      of Life Scale (WHOQOL-BREF). The hallucination, positive formal thought, and
      total SAPS scores of the patients in the experimental group obtained during their
      hospitalisation were determined to be higher than those obtained at discharge and
      at follow-ups after discharge. The characteristics of auditory hallucination
      questionnaire scores of the patients in the experimental and control groups
      decreased. The physical, mental, environmental, and national environmental domain
      scores of the quality of life in the experimental group increased at sixth month
      after discharge. Listening to music had positive effects on positive symptoms and
      the quality of life of patients with auditory hallucination. In line with these
      results, listening to music may be recommended to cope with auditory
      hallucinations and to provide positive quality of life.

PMID- 30111214
TI  - Use of Emergency Medical Services by Police.
AB  - OBJECTIVES: Many police officers receive medical training for limited assessments
      and interventions. In most situations where medical issues arise, however,
      emergency medical services (EMS) are called for evaluation, treatment, and
      transport. Given the limited amount of information about such encounters we
      examined officer calls for EMS help in a single system to better describe these
      encounters. METHODS: Requests for medical help from a fire-based EMS system by
      police in a moderate-sized city in 2014 and 2015 were identified. In this system,
      fire department resources are requested for initial evaluations of any medical
      complaint. Data were extracted from fire records including disposition,
      transportation from scene, type of injury or illness, and vital signs. Data
      analysis used descriptive statistics. RESULTS: 4,792 calls were made,
      representing 2.2% of all police-citizen interactions and 4.2% of all EMS calls. A
      total of 61.2% of calls resulted in transport to hospital. Of those, 5.6%
      required fire-based advanced life support; the remainder were transported by
      private basic life support ambulance or non-medical means. Most requests were for
      trauma (51.4%), followed by medical (24.7%), drug/alcohol use (17.1%), and
      psychiatric (6.7%). Vital signs tended to be within normal limits including 72.7%
      of pulses, 65.1% of systolic blood pressures, and 90.5% of respiratory rates.
      CONCLUSION: Requests for EMS assistance from police were common. Most calls
      involved patients with normal vital signs who did not require advanced life
      support transport. Further research is needed to identify situations where
      increased officer training and change in protocols could potentially change EMS
      response models and improve efficiency of the system.

PMID- 30111212
TI  - Procalcitonin may not be a differential diagnostic marker for bacterial infection
      in febrile patients with chronic gouty arthritis.
AB  - Objective This study aimed to examine the diagnostic value of serum procalcitonin
      (PCT) levels for identifying bacterial infection in febrile patients with chronic
      gouty arthritis. Methods Sixty-six febrile patients with chronic gouty arthritis
      were divided into non-bacterial infection (n = 45) and bacterial infection groups
      (n = 21). PCT levels were measured by an immunoassay. Other laboratory
      parameters, including the erythrocyte sedimentation rate (ESR), C-reactive
      protein (CRP), white blood cells (WBCs), and the neutrophil ratio were extracted
      from medical records. Receiver-operating characteristic curves were used to
      evaluate diagnostic values and accuracy. Results Serum PCT levels, the ESR, CRP
      levels, WBC count, and neutrophil ratio were not different between the groups. To
      assess the ability of PCT to discriminate bacterial infection in febrile patients
      with chronic gouty arthritis (cut-off value: 0.5 ng/mL), the sensitivity and
      specificity of PCT were 22.2% and 61.5%, respectively. The area under the curve
      (AUC) of serum PCT levels was 0.526. The AUCs of related inflammatory indicators
      were 0.530 for the ESR, 0.635 for CRP, 0.577 for the WBC count, and 0.712 for the
      neutrophil ratio. Conclusion Serum PCT levels may not be a good biomarker for
      bacterial infection in febrile patients with chronic gouty arthritis.

PMID- 30111215
TI  - The Expression of Calprotectin and Factors in TLR4/NF-kappaB/MyD88 Pathway in
      Patients with Idiopathic Acute Anterior Uveitis.
AB  - PURPOSE: The purpose of the article is to investigate the contribution of
      calprotectin and factors in toll-like receptor 4/nuclear factor-kappaB/myeloid
      differentiation factor 88 (TLR4/NF-kappaB/MyD88) pathway in patients with
      idiopathic acute anterior uveitis (IAAU). METHODS: In total, 72 patients with
      IAAU and 56 healthy individuals were enrolled. Serum calprotectin, TLR-4, and
      MyD88 were determined. Best-corrected visual acuity, uveitis activity grading,
      and macular thickness measured by optical coherence tomography were performed.
      RESULTS: Serum calprotectin, TLR4, and MyD88 levels were higher in IAAU group
      than those in healthy individuals. Serum calprotectin level was positively
      correlated with uveitis activity grading and macular thickness. Receiver
      operating characteristic curve analysis showed serum calprotectin had larger area
      under curve than serum TLR4 and MyD88. CONCLUSIONS: The calprotectin and TLR4/NF
      kappaB/MyD88 signal might contribute to the pathogenesis of IAAU and serum
      calprotectin might be a specific biomarker for the measurement of ocular
      inflammation in IAAU.

PMID- 30111216
TI  - Optimal concentration of the transversus abdominis plane block in enhanced
      recovery after surgery protocols for patients of advanced age undergoing
      laparoscopic rectal cancer surgery.
AB  - OBJECTIVE: The transversus abdominis plane (TAP) block ameliorates visual
      analogue scale scores and decreases morphine requirements, but its role remains
      unclear. Patients of advanced age are susceptible to local anesthetic
      intoxication. We aimed to identify an optimal concentration that can be used in
      enhanced recovery after surgery (ERAS) without compromising analgesic efficacy.
      METHODS: In total, 120 patients aged >=65 years undergoing laparoscopic rectal
      cancer surgery received general anesthesia combined with a TAP block using 0.25%
      ropivacaine (Group A), 0.50% ropivacaine (Group B), or 0.75% ropivacaine (Group
      C) in a 40-mL volume. Group D only received general anesthesia. Epinephrine,
      plasma cortisol, interleukin-6, and tumor necrosis factor-alpha were measured at
      baseline, skin incision, celiac exploration, and tracheal extubation. The
      proportions of CD4+ and CD4+/CD8+ cells were measured at baseline and
      postoperative days 1 and 3. RESULTS: The TAP block relieved the stress response
      and accelerated intestinal functional recovery as shown by significant reductions
      in VAS scores and anesthetic requirements. However, there was no significant
      difference between Groups B and C. CONCLUSION: The TAP block plays an important
      role in ERAS in older patients undergoing laparoscopic rectal cancer surgery, and
      0.5% ropivacaine is an optimal concentration that can reduce toxicity without
      undermining analgesia.

PMID- 30111218
TI  - Next-generation DNA sequencing analysis of two Streptococcus suis ST28 isolates
      associated with human infective endocarditis and meningitis in Gunma, Japan: a
      case report.
AB  - Streptococcus suis (S. suis) is an important emerging zoonotic agent. Here, we
      report two cases of S. suis infection in pig farmers in Gunma Prefecture, Japan.
      We conducted a high-resolution molecular epidemiologic analysis on the basis of
      whole-genome sequencing data of each isolate using next-generation sequencing
      (NGS). NGS analysis revealed that the two S. suis clinical isolates were belonged
      to serotype 2 ST28. Phylogenetic analysis showed that two isolates were closely
      related to S. suis strains isolated from pigs in Japan at least until 1995. Since
      41 nucleotide substitutions were found between the two strains, these strains
      might be derived from the same genetic lineage but distinct sporadic cases. NGS
      analysis is a powerful diagnostic tool for analysing bacterial infections. The
      database is more fulfilling, and more detailed analysis will become possible in
      the near future. Attention should be paid to S. suis infections, especially if
      the patient works on a livestock farm.

PMID- 30111217
TI  - Analysis of serum alpha-fetoprotein (AFP) and AFP-L3 levels by protein
      microarray.
AB  - Objectives This study aimed to examine a simple, effective, time-saving, and low
      cost protein microarray method for detecting serum alpha-fetoprotein (AFP) and
      AFP-L3 levels. Methods Serum samples from patients with hepatocellular carcinoma
      (HCC) (n = 33) and control subjects (n = 39) were collected and evaluated for the
      presence of AFP using a novel protein microarray. Glycoprotein (including AFP-L3)
      was enriched from crude samples by a Hotgen Biotech glycosyl capture spin column
      and then detected by protein microarray. An electrochemiluminescence immunoassay
      (ECLIA) was used to validate the measured values. Results Neither AFP levels
      lower than 20 ng/mL in the HCC group nor AFP levels higher than 20 ng/mL in the
      control group were found when tested by the ECLIA and protein microarray. The
      kappa test showed good consistency in the diagnostic performance of measuring
      serum AFP levels and the percentage of AFP-L3 in total AFP by the ECLIA and
      protein microarray. Protein microarray had advantages of smaller sample size
      required, low cost, and convenience compared with the ECLIA. Conclusion The
      protein microarray assay that was developed in the present study shows potential
      as an economic and convenient technique for detecting AFP and AFP-L3 levels in
      serum samples from patients with HCC.

PMID- 30111219
TI  - Adolescent Substance Use and Effects on the Birth Experience.
AB  - Depression, violence, and infant complications are recognized risk factors for
      negative birth experiences. Substance use, which often co-occurs with these risk
      factors, is unexplored for its role upon the birth experience. The frequency of
      these risk factors among childbearing adolescents suggests a need for research in
      this area. This study revealed direct and indirect effects by all risk factors on
      the adolescent's birth experience. Implications for nursing practice suggest
      collaboration between maternal child health and mental health nurses in prenatal,
      hospital, and follow-up healthcare settings to provide essential assessment of
      risk factors and resources and referrals across the perinatal period.

PMID- 30111221
TI  - Enhancement of anti-tumor effect of plasmid DNA-carrying MUC1 by the
      adjuvanticity of FLT3L in mouse model.
AB  - AIM: DNA vaccines have emerged as a promising strategy for cancer immunotherapy;
      however, their immunogenicity is weak. Fms-like tyrosine kinase 3-ligand (Flt3L)
      has been exploited for its ability to increase the proliferation of dendritic
      cells (DCs). The aim of the present study was to investigate whether co
      administration of an adjuvant plasmid expressing mouse Flt3L and a DNA vaccine of
      the Mucin 1 (MUC1) antigen enhances immune responses. METHODS: The recombinant
      plasmids pVAX1-MUC1 and pVAX1-Flt3L were constructed and injected into mice
      intramuscularly (i.m.), followed by electroporation. The humoral and cellular
      immune responses after immunization were examined by enzyme linked immunosorbent
      assay (ELISA) and enzyme-linked immunospot assay (ELISPOT), respectively. To
      evaluate the anti-tumor efficacy of the plasmids, a mouse model of MUC1
      expressing tumors was established. RESULTS: The results showed that co
      administration of an adjuvant plasmid and a DNA vaccine stimulated the production
      of higher titers of specific antibodies and a T cell response and suppressed the
      growth of subcutaneous tumors expressing MUC1. Collectively, our results indicate
      that a plasmid expressing murine Flt3L could stimulate stronger immune responses.
      CONCLUSION: These observations emphasize the potential of Flt3L as an adjuvant
      for colon cancer DNA vaccines.

PMID- 30111220
TI  - Prevalence of Foot Complications in People With Type 2 Diabetes Mellitus: A
      Community-Based Survey in Rural Udupi.
AB  - The objective of the study was to determine the prevalence of foot complications
      among people with type 2 diabetes mellitus in the rural part of Udupi district,
      Karnataka, India. A cross-sectional observational study design was conducted in
      the rural area of Udupi district. In the study, accredited social health
      activists were trained to screen people with type 2 diabetes mellitus for
      diabetic foot complications at a community level. Adults over 35 years of age
      were screened for the presence of type 2 diabetes mellitus by accredited social
      health activists who reside in the rural part of Udupi district. Participants
      with type 2 diabetes mellitus were included in the study. Blood glucose level was
      measured using a glucometer. Foot examination was done by visual inspection,
      monofilament, tuning fork, and pedal pulse. In the present study, 2110 among the
      total participants were found to have type 2 diabetes mellitus. The prevalence of
      musculoskeletal foot complications was 1218 (58%), vascular problem 466 (22.2%),
      sensory neuropathy 634 (30.2%), autonomic neuropathy 1729 (81.9%), ulcer 134
      (6.38%), and infection 561 (26.7%) among people with type 2 diabetes mellitus. In
      the current study, we found 84.7% of people residing in rural Udupi had type 2
      diabetes mellitus. Hence, there is a strong need to create awareness about
      diabetic foot care in these people.

PMID- 30111222
TI  - Automated External Defibrillator Geolocalization with a Mobile Application,
      Verbal Assistance or No Assistance: A Pilot Randomized Simulation (AED G-MAP).
AB  - OBJECTIVE: Shockable rythms are common among victims of witnessed public out-of
      hospital cardiac arrest (OHCA), but bystander defibrillation with a public
      automated external defibrillator (PAED) is rare. Instructions from the emergency
      medical dispatcher and mobile applications were developed to expedite the
      localization of PAEDs, but their effectiveness has not been compared. METHODS:
      Participants were enrolled in a three-armed randomized simulation where they
      witnessed a simulated OHCA on a university campus, were instructed to locate a
      PAED and provide defibrillation. Participants were stratified and randomized to:
      (1) no assistance in finding the PAED, (2) assistance from a geolocalization
      mobile application (AED-Quebec), or (3) verbal assistance. Data collectors
      tracked each participant's time elapsed and distance traveled to shock. RESULTS:
      Of the 52 volunteers participating in the study (46% male, mean age 37), 17 were
      randomized to the no assistance group, 18 to the mobile application group and 17
      to the verbal group. Median (IQR) time to shock was, respectively, 10:00 min
      (7:49-10:00), 9:44 (6:30-10:00), and 5:23 (4:11-9:08), with statistically
      significant differences between the verbal group and the other groups (p <=
      0.01). The success rate for defibrillation in <10 minutes was 35%, 56% and 76%.
      Multivariate regression of all participants pooled showed that knowledge of
      campus geography was the strongest predictor of shock in <10 minutes (aOR =14.3,
      95% CI 1.85-99.9). Among participants without prior geographical knowledge,
      verbal assistance provided a trend towards decreased time to shock, but the
      differences over no assistance (7:28 vs. 10:00, p = 0.10) and over the mobile app
      (7:28 vs. 10:00, p = 0.11) were not statistically significant. CONCLUSION: In a
      simulated environment, verbally providing OHCA bystanders with the nearest PAED's
      location appeared to be effective in reducing the time to defibrillation in
      comparison to no assistance and to an AED geolocalizing mobile app, but further
      research is required to confirm this hypothesis, ascertain the external validity
      of these results, and evaluate the real-life implications of these strategies.

PMID- 30111223
TI  - Open reduction and internal fixation of intra-articular distal radius fractures
      under wide-awake local anesthesia with no tourniquet.
AB  - Objective The use of wide-awake local anesthesia with no tourniquet (WALANT) is
      becoming an excellent alternative for elective hand surgeries and hand surgeries
      involving minor trauma. Although the use of WALANT for some soft tissue surgeries
      has become the state of the art, data regarding bony procedures, such as fracture
      management, under WALANT are limited. This study was performed to assess the
      WALANT technique for open reduction and internal fixation of distal radius
      fractures. Methods Five patients with displaced distal radius fractures were
      enrolled in the study. WALANT was carried out about 30 minutes prior to the first
      incision. Surgery was performed in the normal fashion, and the fractures were
      fixed using anatomic locking plates. After surgery, the patients were admitted
      overnight for observation and pain assessment, and they were discharged within 24
      hours postoperatively. Intraoperative and postoperative complications were
      recorded. Follow-up was performed in our outpatient clinic. No abnormalities were
      recorded. Results All patients underwent a successful painless surgery. No extra
      bleeding or other complications were recorded. Conclusion The WALANT technique
      offers a simple and safe alternative to traditional anesthetic techniques for
      open reduction and plating of distal radius fractures.

PMID- 30111225
TI  - Acute Kidney Injury Following Methimazole Initiation: A Case Report.
AB  - OBJECTIVE: Nephritis has been rarely associated with methimazole, primarily in
      the development of nephrotic syndrome. We describe a case of acute kidney injury
      without evidence of nephrotic syndrome following methimazole initiation. METHODS:
      We present the relevant history, laboratory data, and nuclear medicine data and
      review relevant documentation from the literature. RESULTS: A 72-year-old male
      recently diagnosed with new-onset atrial fibrillation was found to have
      suppressed thyroid-stimulating hormone (TSH) levels; elevated free T3, T4, and
      thyroid-stimulating immunoglobulin (TSI) levels; and a nonnodular thyroid gland
      with normal iodine uptake. He was diagnosed with Graves' disease and treated with
      propylthiouracil (PTU) for 5 years. When his poor compliance with PTU was
      impeding his antithyroid treatment, he was converted to methimazole. Within 1
      month following methimazole initiation, his serum creatinine (SCr) had risen to
      1.6* baseline in the absence of other contributing nephrotoxins. SCr returned to
      baseline within 2 weeks of methimazole discontinuation, and the patient was
      subsequently managed on PTU. CONCLUSION: Acute kidney injury with or without the
      presence of nephrotic syndrome may occur during treatment with methimazole. Renal
      function should be closely monitored after the initiation of methimazole to
      prevent progressive renal dysfunction.

PMID- 30111224
TI  - Factors associated with poor adherence to vaccination against hepatitis viruses,
      streptococcus pneumoniae and seasonal influenza in HIV-infected adults.
AB  - INTRODUCTION: Vaccination against various pathogens is recommended for HIV
      positive adults. There are not sufficient data either on vaccination coverage of
      HIV positive adults or the risk factors associated with poor adherence to routine
      vaccination. PATIENTS-METHODS: During the period 2004-2014 vaccination coverage
      of a group of HIV infected adults against hepatitis A virus (HAV), hepatitis B
      virus (HBV), seasonal influenza virus and pneumococcal disease was recorded.
      Vaccination coverage was separated into two chronological periods, before and
      after 2010, as 2010 marks the start of the economic crisis in Greece. RESULTS:
      1210 patients were included in our study. Vaccine coverage throughout the study
      for hepatitis B, hepatitis A, seasonal influenza and pneumococcal infection was
      73.6%, 70.4%, 39% and 79%, respectively. The complete lack of insurance coverage
      was an independent factor of non-compliance in all proposed vaccines (vaccination
      against pneumococcal disease: OR: 0.82 95%CI: 0.49-1.35, vaccination against HBV:
      OR: 0.82, 95% CI: 0.45-1.49, vaccination against HAV OR: 0.54, 95%CI: 0.34-0.87,
      vaccination against influenza: OR: 1.27, 95% CI: 0.76-2.10). In addition, low
      educational level was associated with poor compliance to vaccination against
      pneumococcal disease, hepatitis A, hepatitis B, and influenza. Finally, the
      recommendation for vaccination after the onset of the economic crisis (2010) led
      to poor compliance to vaccination against HBV, HAV and pneumococcal disease, but
      not against influenza. CONCLUSIONS: In our study, vaccination coverage for
      vaccine-preventable diseases was found to be insufficient for HIV positive adults
      in Northern Greece. Also, low educational level, lack of insurance coverage and
      economic distress have contributed to poor vaccine compliance, leading to poor
      protection of the HIV positive population and decreased immune coverage in the
      community.

PMID- 30111226
TI  - Induction of GPR40 positively regulates cell motile and growth activities in
      breast cancer MCF-7 cells.
AB  - Free fatty acid (FFA) receptors belong to a member of G-protein-coupled
      receptors. GPCR 120 (GPR120) and GPR40 are identified as FFA receptors and
      activated via the binding of long- and medium-chain FFAs. The aim of this study
      was to assess the effects of GPR120 and GPR40 on cell motility and growth in
      breast cancer cells treated with tamoxifen (TAM). MCF-7 cells were continuously
      treated with TAM for approximately 6 months. The expression level of GPR40 gene
      was markedly higher in the long-term TAM treated (MCF-TAM) cells than in MCF-7
      cells. In cell motility assay, MCF-TAM cells indicated the high cell motile
      activity, compared with MCF-7 cells. The cell motile activity of MCF-TAM cells
      was suppressed by a selective GPR40 antagonist, GW1100. To evaluate the effects
      of GPR40 on cell growth activity under estrogen-free conditions, cells were
      maintained in serum-free DMEM without phenol red for 2 days. In estrogen-free
      conditioned medium, the cell growth rate of MCF-TAM cells was significantly
      higher than that of MCF-7 cells. In addition, treatment of GW1100 reduced the
      cell growth rate of MCF-TAM cells. These results suggest that the cell motile and
      growth activities may be positively regulated through the induction of GPR40 by
      the long-term TAM treatment in MCF-7 cells.

PMID- 30111227
TI  - Parenting and perinatal depression: meeting women's needs.
AB  - INTRODUCTION: Symptoms of depression during pregnancy and the postpartum period
      can negatively impact parenting. It is important to understand the parenting
      experiences of women with depression, and what parenting support they need.
      METHODS: This is a mixed methods analysis of data (demographic data, depression
      outcomes, patient survey results, and transcripts of patient and care manager
      focus groups) from an open treatment trial of the feasibility of delivering
      perinatal depression treatment using collaborative care in a rural obstetric
      setting. RESULTS: Patients who attended focus groups did not differ significantly
      from those who did not. Qualitative analysis of focus groups revealed the
      following themes: Maternal mood and parenting difficulties are interrelated;
      Access to depression treatment is complicated by expectations for the perinatal
      period and by factors related to parenting; Women want parenting support in the
      context of treatment for perinatal depression. CONCLUSION: Women receiving
      perinatal depression treatment experience unique parenting challenges and desire
      parenting support. Healthcare providers caring for these women should be mindful
      of their patients' parenting needs. Future research should explore ways to
      integrate parenting interventions with depression treatments. Mother-infant
      interaction is a key determinant of optimal infant development and integrating
      parenting support with perinatal depression treatments can have significant
      public health impact.

PMID- 30111228
TI  - A Novel, Automated Dispersive Pipette Extraction Technology Greatly Simplifies
      Catecholamine Sample Preparation for Downstream LC-MS/MS Analysis.
AB  - Catecholamines are integral neurotransmitters in the central and peripheral
      nervous system. Clinically, catecholamine levels are determined to help diagnose
      disease and measure corresponding therapeutic effectiveness. However, manual
      extraction of catecholamines and their metabolites may be labor-intensive and
      user-variable and require a variety of peripheral laboratory devices, especially
      at low sample concentrations. Here, we propose a novel solid-phase extraction
      (SPE) method using patented dispersive pipette extraction (DPX) tip technology.
      The tips are readily integrated into an automated workflow to extract these
      compounds from urine, which increases analytical throughput while removing human
      variability and error. Diphenylboronic acid (DPBA) forms a stable, negatively
      charged complex with catecholamines in the samples, and when aspirated into the
      DPX tip, the complexed analytes are retained on a styrene divinyl benzene
      sorbent. Wash buffers remove interfering compounds, after which the complex is
      eluted from the tip using an acidic aqueous solution and subsequently measured
      via liquid chromatography with tandem mass spectrometry (LC-MS/MS). The automated
      DPX method for catecholamine sample preparation from urine has excellent
      linearity over more than three orders of magnitude with concentrations ranging
      from 0.5 to 1000 ng/mL, with replicate analyses resulting in coefficients of
      variation of less than 8%. This high-throughput workflow is appropriate for use
      in regulated laboratories.

PMID- 30111229
TI  - Delay discounting of monetary gains and losses in adolescents with ADHD:
      Contribution of delay aversion to choice.
AB  - Adolescents with attention-deficit/hyperactivity disorder (ADHD) are known to
      have stronger preferences for smaller immediate rewards over larger delayed
      rewards in delay discounting tasks than their peers, which has been argued to
      reflect delay aversion. Here, participants performed a delay discounting task
      with gains and losses. In this latter condition, participants were asked whether
      they were willing to wait in order to lose less money. Following the core
      assumption of the delay aversion model that individuals with ADHD have a general
      aversion to delay, one would predict adolescents with ADHD to avoid waiting in
      both conditions. Adolescents (12-17 years) with ADHD (n = 29) and controls (n =
      28) made choices between smaller immediate and larger delayed gains, and between
      larger immediate and smaller delayed losses. All delays (5-25 s) and gains/losses
      (2-10 cents) were experienced. In addition to an area under the curve approach, a
      mixed-model analysis was conducted to disentangle the contributions of delay
      duration and immediate gain/delayed loss amount to choice. The ADHD group chose
      the immediate option more often than controls in the gain condition, but not in
      the loss condition. The contribution of delay duration to immediate choices was
      stronger for the ADHD group than the control group in the gain condition only. In
      addition, the ADHD group scored higher on self-reported delay aversion, and delay
      aversion was associated with delay sensitivity in the gain condition, but not in
      the loss condition. In sum, we found no clear evidence for a general aversion to
      delay in adolescents with ADHD.

PMID- 30111230
TI  - Researching and Designing Health Care Environments: A Systematized Review of
      Creative Research Methods.
AB  - In research and design, Creative Research Methods (CRMs) are useful to gain
      insight into user perspectives. Reviews suggest that CRMs offer potential to
      engage people, yet little detail is available regarding their use in relation to
      built health care environments. Consider environments for cancer care, where
      patients are confronted with particular physical and emotional challenges. This
      review aims to synthesize what is known from existing literature about CRMs
      exploring user experience when researching and designing (cancer) care
      environments. Based on 16 items, we evaluate the potential of CRMs, offering
      insight into why, how, where, and when they are employed. Generally little
      consideration is shown for participants' abilities and limitations. Our analysis
      further emphasizes the importance of reflecting on visual methods, and the need
      to report research approaches transparently including where CRMs are used. A
      sophisticated research approach can leverage CRMs' potential to study experience
      and carry artifacts forward to inform design(ers).

PMID- 30111231
TI  - Confirmatory factor analysis of the behavior rating inventory of executive
      function in a neuro-pediatric sample and its application to mental disorders.
AB  - The construct validity of the 9-scale version of the Behavior Rating Inventory of
      Executive Function (BRIEF) parent form was examined in a clinical sample of
      children and adolescents with neurological and neurodevelopmental disorders (N =
      281). Confirmatory factor analysis supported a three-factor model separating the
      inhibitory behavioral control dimension from the emotional control and
      metacognitive problem-solving dimensions. The Metacognitive factor was also
      related to a diagnosis of attention deficit/hyperactivity disorder (ADHD) after
      controlling for age, gender, IQ, adaptive functioning, and a conventional
      behavioral rating scale, which included inattention-hyperactivity symptoms. The
      Emotional Regulation factor was related to a diagnosis of oppositional defiant
      disorder. Correlational analyses indicated that child comorbid emotional and
      behavioral problems may exacerbate parental BRIEF reporting. Accordingly, when
      assessing executive function among children with neurological and
      neurodevelopmental disorders, the BRIEF should be complemented with assessments
      of mental health problems.

PMID- 30111232
TI  - CIMT 2018: Pushing frontiers in cancer immunotherapy - Report on the 16th Annual
      Meeting of the Association for Cancer Immunotherapy.
AB  - The 16th Annual Meeting of the Association for Cancer Immunotherapy (CIMT),
      Europe's largest meeting series of its kind, took place in Mainz, Germany from 15
      17 May, 2018. Cutting-edge advancements in cancer immunotherapy were discussed
      among more than 700 scientists under the motto "Pushing Frontiers in Cancer
      Immunotherapy". This meeting report is a summary of some of the CIMT 2018
      highlights.

PMID- 30111233
TI  - A Pilot Randomized Controlled Trial Examining the Effects of Tai Chi and
      Electronic Tablet Use on Older Adults' Cognition and Health.
AB  - PURPOSE: To evaluate the feasibility of Tai Chi (TC) and electronic tablet (ET)
      interventions on older adults' cognition and health and to explore participants'
      perceptions of intervention activities. DESIGN: An emergent embedded experimental
      mixed methods design was used in which the qualitative strand helped explain
      intervention results. METHOD: Older adults who participate in TC classes will
      have improved cognition and health compared with older adults who participate in
      ET classes. Twenty-six participants from two assisted living residences were
      recruited and randomized to receive nine TC or ET classes. The Modified Mini
      Mental State Exam was used to measure cognition and the SF-12v2 assessed
      perceived health before and after the intervention. Participants were invited to
      share perceptions of the two interventions. Institutional review board approval
      was obtained and participants provided signed consent for both quantitative and
      qualitative strands. FINDINGS: There was no significant difference within or
      between groups on cognition and health scores. CONCLUSIONS: TC and ET use are
      activities that can be delivered in the community and have the potential to
      promote compensatory scaffolding as described by the revised scaffolding theory
      of aging and cognition. Future research should involve larger samples and
      teaching methods that promote learning postures.

PMID- 30111234
TI  - Influencing Exercise and Hydration Self-Care Practices of Baccalaureate Nursing
      Students.
AB  - PURPOSE: Health promotion is often neglected by students during their nursing
      education, yet research indicates that self-care practices can significantly
      reduce compassion fatigue and burnout. An intervention study investigated
      strategies to increase exercise and hydration in baccalaureate nursing students.
      METHOD: Using a convenience sample ( n = 73), data were collected through pre-
      and postsurveys of nursing students participating in an 8-week period that
      focused on strategies to increase walking and drinking water. FINDINGS: Several
      significant trends emerged from the study participants ( n = 21). Younger (18-25
      years) students perceived their health status as excellent to good, while older
      (26-50+ years) students viewed their health status as fair to poor. Although no
      significant difference in exercise occurred between pre- and postsurvey, a trend
      of an increase in frequency was noted. A dramatic increase of nearly 16 ounces in
      water consumption was reported on both clinical ( p = .032) and nonclinical ( p =
      .028) days. The findings are supported by Pender's health promotion model concept
      of self-efficacy. CONCLUSION: The frequency of exercise and amount of hydration
      increased during the 8-week intervention period. Despite a small sample size and
      short intervention period, results merit further research on the positive
      influences of self-care practices in nursing students.

PMID- 30111235
TI  - Nurse performed peripheral intravenous catheter first time insertion success in
      pediatric patients in Bhutan: An observational study.
AB  - INTRODUCTION: Peripheral intravenous catheter insertion is a clinical procedure
      commonly performed by nurses for pediatric patients in Bhutan. This study
      describes peripheral intravenous catheter first attempt success and factors
      associated with such insertions. METHODS: A cross-sectional survey was conducted
      from October 2016 to March 2017, comprised of a national sample of the Bhutan
      pediatric patient population (0-12 years). We collected data on peripheral
      intravenous catheter first time insertion success rate of admitted pediatric
      patients, to identify predictors of a successful first time attempt. Clustered
      log binomial generalized linear models were used to obtain the prevalence of
      first time attempt success and predictors of success. RESULTS: The prevalence
      rate of successful first time attempt adjusted for clustering was 64% (95%
      confidence interval: 51%-80%). Predictors of a successful first time attempt were
      older patient age, lighter skin color, the vein being visible with a tourniquet,
      and the left hand being used for insertion. A transilluminator was used in 52
      patients, and the peripheral intravenous catheter was eventually successfully
      placed in 82% of the patients. DISCUSSION: Our first time successful cannulation
      rate is substantially lower than that found in similar studies in other
      countries. Considering the impact a peripheral intravenous catheter has on
      patients' clinical outcomes and cost implications, reducing the number of failed
      attempts should be of high importance. Better education and simulation, combined
      with the adoption of vessel locating technology, are required to improve
      insertion practice in Bhutan. This could lead to greater efficiency of the health
      facilities in Bhutan.

PMID- 30111236
TI  - Corrigendum.

PMID- 30111237
TI  - Psychometric validation of the Arthritis Helplessness Index in systemic lupus
      erythematosus.
AB  - Objective Helplessness is a relevant construct in systemic lupus erythematosus
      (SLE), an unpredictable chronic illness with no known cure characterized by
      relapsing and remitting features. However, no measure of helplessness has been
      validated in this population. The present study examined the structural validity,
      reliability, and convergent validity of the Arthritis Helplessness Index, a
      measure initially developed for rheumatoid arthritis populations, in a sample of
      patients with SLE. Methods Patients with SLE ( N = 136) receiving medical care at
      a private hospital completed the Arthritis Helplessness Index and other self
      report measures. The structural validity of the Arthritis Helplessness Index was
      examined using confirmatory factor analysis. Internal consistency reliability was
      evaluated with Cronbach's coefficient alpha. Pearson product-moment correlations
      were used to examine convergent validity with measures of depression, anxiety and
      mastery. Results The five-item Arthritis Helplessness Index-Helplessness measure
      demonstrated a tenable factor structure (comparative fit index 0.98, root mean
      square error of approximation 0.06, standardized root mean residual 0.04).
      Internal consistency reliability was fair (alpha = 0.69). Convergent validity was
      evidenced by significant correlations with measures of depression, anxiety and
      mastery. Conclusion The five-item Arthritis Helplessness Index-Helplessness scale
      can confidently be used as a measure of helplessness in SLE.

PMID- 30111238
TI  - An imbalance in the T-helper phenotypes displayed by senescent CD4+CD28null T
      cells is associated with erosive arthritis (rhupus syndrome) in systemic lupus
      erythematosus.
AB  - OBJECTIVE: The objective was to assess the proportion of Th1, Th2 and Th17
      phenotypes in senescent CD4+CD28null cells from patients with systemic lupus
      erythematosus (SLE) and its association with the pattern of joint involvement.
      METHODS: This cross-sectional study was performed in SLE patients with erosive
      arthritis (rhupus) or nondeforming, nonerosive arthritis. Total CD4+CD28null
      cells as well as the proportion of these cells expressing T-bet, GATA3 or
      RORgammat were analyzed by color-flow cytometry. Serum osteopontin levels were
      measured by ELISA. RESULTS: Eighteen SLE patients (nine with rhupus and nine with
      nonerosive arthritis) were studied. The percentage of CD4+CD28null/CD4+ cells
      (17.7%, 10.3-25.0% versus 9.4%, 8.1-22.4%; P = 0.386) as well as the osteopontin
      levels (5800, 5,134-5995 pg/ml versus 5578, 5171-5717 pg/ml; P > 0.05) were
      similar in both groups. A higher percentage of CD4+CD28nullT-bet+ cells (42.8%,
      33.5-53.4% versus 30.0%, 23.3-34.2%) but a lower percentage of CD4+CD28nullGATA3+
      cells (3.1%, 1.7-5.6% versus 6.2%, 2.6-18.4%) was observed in patients with
      rhupus than in their counterparts ( P = 0.016). The frequency of
      CD4+CD28nullRORgammat+ cells was similar between groups. CONCLUSIONS: In patients
      with rhupus, senescent CD4+CD28null cells are preferentially polarized to a Th1
      phenotype, whereas this is partial towards Th2 in lupus patients with a
      nonerosive arthritis pattern.

PMID- 30111240
TI  - Vibration therapy versus standard treatment for tennis elbow: A randomized
      controlled study.
AB  - AIM: To determine whether a mechanical, high-frequency vibration device
      (TeneaseTM) can improve pain and function for the treatment of tennis elbow (TE),
      compared with standard treatment. METHODS: Adults presenting to an elbow clinic
      with a clinical diagnosis of TE were randomized to standard treatment with
      physiotherapy, activity modification and analgesia or standard treatment plus
      Tenease therapy. Tenease therapy consisted of a 6-week period of treatment using
      the Tenease device with three 10-min episodes each day. The primary outcome
      measure was the quick Disabilities of the Arm, Shoulder and Hand score at 6
      months, with scores also taken at 6 weeks. Secondary outcome measures were the
      Patient Rated Tennis Elbow Evaluation Score and EuroQol 5-Dimension Visual
      Analogue Scale at the same time points. RESULTS: Fifty-four patients were
      recruited into the study. Following randomization and initial dropout, 18
      patients were included in the standard group and 27 in the Tenease group. Both
      groups reported improvements in primary outcome measure scores. The control group
      had a mean score of 44.3 (standard deviation (SD) = 18.8) at baseline, which
      dropped to 31.2 (SD = 17.2) at 6 months ( p = 0.002). The Tenease group had a
      mean score of 43.2 (SD = 22.7) at baseline, which dropped to 23.4 (SD = 15.0) at
      6 months ( p = 0.064). Similar improvements were seen in secondary outcome
      measures with none reaching statistical significance. There were no statistically
      significant differences seen between the primary outcome scores at 6 weeks ( p =
      0.9) or 6 months ( p = 0.5). No complications were noted in either group.
      CONCLUSIONS: Vibration therapy did not result in any statistically significant
      improvement in functional outcome scores compared to standard treatment for TE.
      It is important to note that this was a relatively small cohort and a high
      dropout rate was observed.

PMID- 30111241
TI  - School Selection and the Social Class Divide: How Tracking Contributes to the
      Reproduction of Inequalities.
AB  - Selection practices in education, such as tracking, may represent a structural
      obstacle that contributes to the social class achievement gap. We hypothesized
      that school's function of selection leads evaluators to reproduce social
      inequalities in tracking decisions, even when performance is equal. In two
      studies, participants (students playing the role of teachers, N = 99, or
      preservice and in-service teachers, N = 70) decided which school track was
      suitable for a pupil whose socioeconomic status (SES) was manipulated. Although
      pupils' achievement was identical, participants considered a lower track more
      suitable for lower SES than higher SES pupils, and the higher track more suitable
      for higher SES than lower SES pupils. A third study ( N = 160) revealed that when
      the selection function of school was salient, rather than its educational
      function, the gap in tracking between social classes was larger. The selection
      function of tracking appears to encourage evaluators to artificially create
      social class inequalities.

PMID- 30111242
TI  - Using the main elbow flexion skin crease as an intraoperative parameter to
      determine the degree of exorotation needed for humeral derotational osteotomies
      in upper-type brachial plexus patients.
AB  - : Even though one of the surgical techniques most frequently used to correct
      external rotation deformity of the shoulder in brachial plexus patients is a
      humeral derotational osteotomy, few intraoperative parameters has yet been
      identified to determine the appropriate degree of rotation. We present in this
      technical note our initial experience using the main elbow flexion skin crease to
      quantify the correct rotation of the humerus in four young, male patients with
      upper-type brachial plexus injuries. All patients had a functional elbow and a
      stable shoulder, but also an external rotation deficit. Via a deltopectoral
      approach, we used the main elbow flexion crease as an intraoperative surgical
      parameter to determine the degree of external rotation of the humerus required to
      achieve a better positioning of the hand in space. After surgery, increased elbow
      flexion range and enhanced hand-to-face movement was observed, while internal
      rotation was preserved for performing midline activities. Moreover, all patients
      exhibited increased active elbow flexion and osteotomy consolidation, with mean
      elbow flexion increasing from 66.3 degrees  to 97.5 degrees  pre to
      postoperatively, and a mean 56.3 degrees  of internal rotation correction
      ultimately achieved. We propose that the main elbow flexion crease is a useful
      intraoperative parameter to determine the degree of intraoperative external
      rotation necessary to restore the plane of hand-face movements in upper-type
      palsies. LEVEL OF EVIDENCE: IV; case series.

PMID- 30111239
TI  - Intracellular displacement of p53 using transactivation domain (p53 TAD) specific
      nanobodies.
AB  - The tumor suppressor p53 is of crucial importance in the prevention of cellular
      transformation. In the presence of cellular stress signals, the negative feedback
      loop between p53 and Mdm2, its main negative regulator, is disrupted, which
      results in the activation and stabilization of p53. Via a complex interplay
      between both transcription-dependent and - independent functions of p53, the cell
      will go through transient cell cycle arrest, cellular senescence or apoptosis.
      However, it remains difficult to completely fathom the mechanisms behind p53
      regulation and its responses, considering the presence of multiple layers
      involved in fine-tuning them. In order to take the next step forward, novel
      research tools are urgently needed. We have developed single-domain antibodies,
      also known as nanobodies, that specifically bind with the N-terminal
      transactivation domain of wild type p53, but that leave the function of p53 as a
      transcriptional transactivator intact. When the nanobodies are equipped with a
      mitochondrial-outer-membrane (MOM)-tag, we can capture p53 at the mitochondria.
      This nanobody-induced mitochondrial delocalization of p53 is, in specific cases,
      associated with a decrease in cell viability and with morphological changes in
      the mitochondria. These findings underpin the potential of nanobodies as bona
      fide research tools to explore protein function and to unravel their biochemical
      pathways.

PMID- 30111243
TI  - Characteristics of Nurse Practitioner Practice in Family Health Teams in Ontario,
      Canada.
AB  - Nurse practitioners (NPs) in Ontario work in a number of settings, including
      physician-led, interprofessional Family Health Teams (FHTs). However, many
      aspects of NP practice within the FHTs are unknown. Our study aimed to describe
      the characteristics of NP practice in FHTs and the relationships between NPs and
      physicians within this model. This cross-sectional descriptive study analyzed NP
      service and diagnostic code data collected for every NP patient encounter from
      2012 to 2015. Encounter data were linked to health administrative data housed at
      the Institute for Clinical Evaluative Sciences to allow for comparison with
      physician service and diagnostic codes. Findings demonstrated that NPs saw
      patients across all age groups for one to more than five problems per encounter
      and that NPs handled both acute and episodic care and chronic disease management
      issues. Patients with chronic conditions had more encounters with physicians than
      with NPs. In addition, compared to physicians, NPs saw more female than male
      patients. Our findings provide a snapshot of NP practice in FHTs and may be
      useful in informing other practice models in Ontario, elsewhere in Canada, and
      internationally. More evidence is needed, however, to clarify the
      responsibilities of the NPs in collaborative relationships with physicians and to
      embed policies that will ensure that NPs work to their full potential. In
      addition, applying service coding to all health care providers in FHTs could
      enhance data on interprofessional teams and the individual clinicians that
      comprise them.

PMID- 30111244
TI  - Single 6-mg dose of rasburicase: The experience in a large academic medical
      center.
AB  - Background Tumor lysis syndrome is an oncologic emergency due to the release of
      tumor cell contents, leading to metabolic derangements. Rasburicase, a
      recombinant urate oxidase, catabolizes uric acid. At our institution, we
      administer a single 6-mg dose of rasburicase to patients who are at risk for
      tumor lysis syndrome. We aimed to assess the efficacy of single 6-mg dose of
      rasburicase and explore risk factors associated with rasburicase failure. Methods
      We report results in 92 adult patients who had a baseline uric acid greater than
      7.5 mg/dL and received a single 6-mg dose of rasburicase for the management of
      tumor lysis syndrome. Responders were defined as those whose uric acid was less
      than or equal to 7.5 mg/dL within 24-36 h of rasburicase administration. The
      primary end point was response based on uric acid level. Secondary end points
      included response to rasburicase in association with lactate dehydrogenase, serum
      creatinine, calcium, phosphorus, blood pH, and oncologic diagnosis. Results
      Median age was 65 years and 70% were men. Most patients had leukemia (32%) or
      lymphoma (40%). Eighty-seven of 92 patients (95%), who received single 6-mg dose
      of rasburicase, achieved a uric acid less than 7.5 mg/dL within 24-36h of dosing.
      Body mass index was similar between responders and non-responders: 28.6 kg/m2 vs.
      26.6 kg/m2, respectively, p = 0.6. Baseline lactate dehydrogenase levels were
      similar between the groups: 756 U/L vs. 892 U/L, respectively, p = 0.33. Blood pH
      values documented within 24 h of first dose of rasburicase were also similar
      between the two groups (n = 30; 7.33 vs. 7.34 respectively, p = 0.6). However,
      median baseline uric acid was lower in responders than non-responders: 12.3 mg/dL
      vs. 17.3 mg/dL, respectively, p = 0.012. Baseline serum creatinine and creatinine
      clearance were similar between responders and non-responders (2.2 mg/dL vs. 3.95
      mg/dL; p = 0.12 and 29 mL/min vs. 16 mL/min; p = 0.11, respectively). Conclusions
      Higher baseline uric acid levels were observed in patients who did not respond to
      the first rasburicase dose. In our study, uric acid levels normalized in 95% of
      patients after a single 6-mg dose of rasburicase indicating that a single 6-mg
      dose of rasburicase may be sufficient to manage tumor lysis syndrome, for most
      patients.

PMID- 30111245
TI  - Effect of a Small Physiological Electric Field on Angiogenic Activity in First
      Trimester Extravillous Trophoblast Cells.
AB  - Electrical stimulation induces significant angiogenesis in vivo. We have shown
      that electrical stimulation of trophoblast cells has important functions in
      aspects of angiogenesis. In this study, we investigated the effects of a direct
      current electrical field on trophoblast angiogenic tube formation. A 6-hour
      exposure to electric fields ranging from 50 to 150 mV/mm dose dependently
      increased tube growth and network formation. Additionally, the effect was time
      dependent, with increased tube formation occurring between 4 and 8 hours,
      indicating stimulation of trophoblast cell angiogenesis. Electrical fields of
      small physiological magnitude stimulated vascular endothelial growth factor
      expression by trophoblast cells in the culture. Electric field treatment also
      resulted in activation of Akt, while the activity of extracellular-regulated
      kinase 1/2, p38, and c-Jun NH2-terminal kinase was not significantly changed.
      Pretreatment with the vascular endothelial growth factor receptor (VEGFR)-2
      inhibitor, SU1498, resulted in potent inhibition of tube growth, and the Akt
      inhibitor, MK-2206 2HCl, significantly reduced electric field-stimulated
      tubulogenesis. These data suggest the importance of the VEGFR-2 signaling pathway
      during electric field-induced trophoblastic angiogenesis. This novel evidence
      indicates that endogenous electrical fields may promote angiogenesis of
      trophoblast cells by stimulating the VEGFR signaling pathway.

PMID- 30111246
TI  - Comparison of intracellular location and stimulus reaction times of forisomes in
      sieve tubes of four legume species.
AB  - Forisomes in legumes are responsible for fast sieve-element occlusion in response
      to injury to the vascular system. This prevents uncontrolled leakage of phloem
      sap and protects against invasion of pathogens. Here we compared forisomes of
      four different legumes (Pisum sativum, Vicia faba, Trifolium pratense and
      Medicago sativa) by their location (basal, central, apical) in the sieve element
      and reactivity to a distant heat stimulus. In each species, the majority of
      forisomes was located basally. Yet, we found differences in intracellular
      location: forisomes are distributed more evenly in the sieve elements of Pisum.
      After burning, basally located forisomes of the four species reacted with
      dispersion, followed by a spontaneous recondensation with similar reaction times.
      The results suggest universal forisome behaviour in fabacean species.

PMID- 30111247
TI  - The Domino Effect: Ed Domino's early studies of Psychoactive Drugs.
AB  - University of Michigan Pharmacology Professor Ed Domino is an expert in the field
      of neuropsychopharmacology. For over six decades, Dr. Domino has made many
      contributions to our understanding of psychoactive drugs, but is most well-known
      for his role in the development of ketamine anesthesia. This article covers the
      story behind this discovery, along with many other fascinating personal and
      professional anecdotes, all of which provide insight into the career of a
      remarkable scientist.

PMID- 30111249
TI  - Evaluation of in situ gelling chitosan-PEG copolymer for use in the spinal cord.
AB  - The goal of the present work was to characterize a hydrogel material for
      localized spinal cord delivery. To address spinal cord injuries, an injectable in
      situ gelling system was tested utilizing a simple, effective, and rapid cross
      linking method via Michael addition. Thiolated chitosan material and maleimide
      terminated polyethylene glycol material were mixed to form a hydrogel and
      evaluated in vitro and in vivo. Three distinct thiolated chitosan precursors were
      made by varying reaction conditions; a modification of chitosan with Traut's
      reagent (2-iminothiolane) displayed the most attractive hydrogel properties once
      mixed with polyethylene glycol. The final hydrogel chosen for animal testing had
      a swelling ratio (Q) of 57.5 +/- 3.4 and elastic modulus of 378 +/- 72 Pa. After
      confirming low cellular toxicity in vitro, the hydrogel was injected into the
      spinal cord of rats for 1 and 2 weeks to assess host reaction. The rats displayed
      no overt functional deficits due to injection following initial surgical recovery
      and throughout the 2-week period after for both the saline-injected sham group
      and hydrogel-injected group. The saline and hydrogel-injected animals both showed
      a similar response from ED1+ microglia and GFAP overexpression. No significant
      differences were found between saline-injected and hydrogel-injected groups for
      any of the measures studied, but there was a trend toward decreased affected area
      size from 1 to 2 weeks in both groups. Access to the central nervous system is
      limited by the blood-brain barrier for noninvasive therapies; further development
      of the current system for localized drug or cellular delivery has the potential
      to shape treatments of spinal cord injury.

PMID- 30111248
TI  - Computed tomography-guided pericardiocentesis: a systematic review concerning
      contemporary evidence and future perspectives.
AB  - BACKGROUND: Pericardial effusion (PE) can develop in several pathological
      scenarios, and is often initially evaluated by means of echocardiography.
      Computed tomography (CT) has been used as an aid in the management of patients
      presenting with PE, in selected cases. The role of CT-guided pericardiocentesis
      in contemporary practice, however, remains not fully ascertained. We aimed at
      presenting a systematic review concerning the state-of-the-art of this technique.
      METHODS: A systematic review of published data on the use of CT for guiding
      pericardiocentesis was carried out (search performed on PubMed, ISI Web of
      Knowledge and Scopus databases). RESULTS: From title and abstract analysis, 14
      articles were included that met the prespecified criteria. After full-text
      analysis, six articles were excluded. The eight articles under analysis included
      a total of 635 procedures performed in 571 patients. CT guidance was mostly used
      in a postoperative setting (364 procedures). Most procedures were done mainly for
      therapeutic purposes (528 procedures). Success rates ranged from 94% to 100%.
      Complications ranged from 0% to 7.8%. CONCLUSION: CT-guided pericardiocentesis is
      a useful technique in the approach to PE, in several clinical scenarios. Its use
      can be especially relevant in the postoperative period, as well as in individuals
      with suboptimal image quality (as assessed by echocardiography, for the moment
      the first choice in the approach to most cases of PE).

PMID- 30111251
TI  - Filling the Void: Hospital Palliative Care and Community Hospice: A Collaborative
      Approach to Providing Hospital Bereavement Support.
AB  - Bereavement services are often provided as components of hospice and palliative
      care plans, including emotional, psychosocial, and spiritual support provided to
      individuals and families to assist with grief, loss, and adjustment after the
      death of a loved one. Patient- and family-centered care is a hallmark of
      palliative care. Moreover, bereavement counseling is offered as a hospice care
      benefit that is covered by Medicare and various private insurance plans. However,
      not all hospital-based palliative care programs offer bereavement support. Many
      bereaved persons whose loved one dies in the hospital while receiving palliative
      care services may not have access to a bereavement support program. This practice
      concept article describes an innovative bereavement program designed to offer
      support to individuals whose loved one died in the hospital while receiving
      palliative care. The bereavement team, including clinical professionals from the
      inpatient palliative care team and two community hospices, developed the
      University of Florida (UF) Health Bereavement Program. The interprofessional team
      includes social workers, volunteers, chaplains, nurses, nurse practitioners, and
      physicians. The Bereavement Program incorporates grief support workshops, follow
      up with participants, via postal mail at timed intervals, website access to grief
      resources, staff education, and an annual evening of remembrance program.
      Finally, interagency collaboration has extended the reach of bereavement services
      beyond UF Health into our community at large.

PMID- 30111250
TI  - Effects of advanced traffic signal status warning systems on vehicle emission
      reductions at signalized intersections.
AB  - Signalized intersections have been identified as vehicle emission hotspots, where
      drivers decelerate, idle, and accelerate their vehicles in response to signal
      changes. Advanced traffic signal status warning systems (ATSSWSs) can be applied
      to reduce traffic emissions at intersections by mitigating unnecessary braking
      and acceleration. In this study, two types of ATSSWSs - variable message sign
      (VMS)-based and vehicle-to-infrastructure (V2I)-based were designed, and their
      environmental effectiveness was evaluated through driving simulator-based
      experiments. Three scenarios were designed and tested: 1) baseline without an
      ATSSWS, 2) with the VMS-based ATSSWS, and 3) with the V2I-based ATSSWS. The Motor
      Vehicle Emission Simulator model was used to evaluate and compare the
      environmental effectiveness of these two types of ATSSWSs. The results indicate
      that the proposed ATSSWSs can reduce traffic emissions at signalized
      intersections. In particular, the V2I-based ATSSWS can substantially reduce CO2,
      NOx, CO, and HC emissions. The results will help transportation practitioners
      with implementing advanced driver information systems and decision-makings on
      emission reduction policies.

PMID- 30111252
TI  - Evaluation of phosphorus removal from a lake by two drinking water treatment
      plants.
AB  - The impact of drinking water treatment plants on phosphorous in a lake has never
      been previously reported. In this mass balance study, phosphorus removal by a
      conventional plant and a membrane plant on Lake Simcoe was monitored.
      Approximately 16 kg of phosphorus per year were removed from the lake by the
      membrane plant, representing 72% of the influent phosphorous load to the plant.
      The membrane plant did not practice coagulation, so approximately two-thirds of
      the removal was via circulation of the treated water to the municipal wastewater
      treatment plant where phosphorous was removed. The remaining third was removed by
      the membranes. The conventional plant removed approximately 10 kg of phosphorus
      per year, representing 92% of the influent phosphorus loading. In this plant,
      polyaluminum chloride coagulation and subsequent sludge removal were responsible
      for approximately two-thirds of the phosphorous removal, with the remainder
      removed via circulation of the treated water to the municipal wastewater
      treatment plant.

PMID- 30111253
TI  - A placebo-controlled randomized trial of D-cycloserine augmentation of cue
      exposure therapy for smoking cessation.
AB  - Recent studies underscore the importance of studying d-cycloserine (DCS)
      augmentation under conditions of adequate cue exposure treatment (CET) and
      protection from reconditioning experiences. In this randomized trial, we
      evaluated the efficacy of DCS for augmenting CET for smoking cessation under
      these conditions. Sixty-two smokers attained at least 18 hours abstinence
      following 4 weeks of smoking cessation treatment and were randomly assigned to
      receive a single dose of DCS (n=30) or placebo (n=32) prior to each of two
      sessions of CET. Mechanistic outcomes were self-reported cravings and physiologic
      reactivity to smoking cues. The primary clinical outcome was 6-week,
      biochemically-verified, continuous tobacco abstinence. DCS, relative to placebo,
      augmentation of CET resulted in lower self-reported craving to smoking pictorial
      and in vivo cues (d = 0.8 to 1.21) in a relevant subsample of participants who
      were reactive to cues and free from smoking-related reconditioning experiences.
      Select craving outcomes were correlated with smoking abstinence, and DCS
      augmentation was associated with a trend toward a higher continuous abstinence
      rate (33% vs. 13% for placebo augmentation). DCS augmentation of CET can
      significantly reduce cue-induced craving, supporting the therapeutic potential of
      DCS augmentation when applied under appropriate conditions for adequate
      extinction learning.

PMID- 30111254
TI  - Trauma-Focused Art Therapy in the Treatment of Posttraumatic Stress Disorder: A
      Pilot Study.
AB  - Research showed that more than 30% of patients with Posttraumatic Stress Disorder
      (PTSD) do not benefit from evidence-based treatments: Trauma-Focused Cognitive
      Behavioral Therapy (TF-CBT) or Eye Movement Desensitization and Reprocessing
      (EMDR). These are patients with prolonged and multiple traumatization, with poor
      verbal memory, and patients with emotional over-modulation. Retelling traumatic
      experiences in detail is poorly tolerated by these patients and might be a reason
      for not starting or not completing the recommended treatments. Due to lack of
      evidence, no alternative treatments are recommended yet. Art therapy may offer an
      alternative and suitable treatment, because the nonverbal and experiential
      character of art therapy appears to be an appropriate approach to the often
      wordless and visual nature of traumatic memories. The objective of this pilot
      study was to test the acceptability, feasibility, and applicability of trauma
      focused art therapy for adults with PTSD due to multiple and prolonged
      traumatization (patients with early childhood traumatization and refugees from
      different cultures). Another objective was to identify the preliminary
      effectiveness of art therapy. Results showed willingness to participate and
      adherence to treatment of patients. Therapists considered trauma-focused art
      therapy feasible and applicable and patients reported beneficial effects, such as
      more relaxation, externalization of memories and emotions into artwork, less
      intrusive thoughts of traumatic experiences and more confidence in the future.
      The preliminary findings on PTSD symptom severity showed a decrease of symptoms
      in some participants, and an increase of symptoms in other participants. Further
      research into the effectiveness of art therapy and PTSD is needed.

PMID- 30111256
TI  - Young Black Men's Information Seeking following Celebrity Depression Disclosure:
      Implications for Mental Health Communication.
AB  - Celebrity health disclosures motivate people to seek information about various
      health topics. However, limited systematic evaluations exist on effects of
      celebrity disclosures of mental illness, despite observations that this is a
      growing phenomenon and have important implications for public health education.
      Further, research has rarely examined the impact of such disclosures on minority
      populations. This study sought to understand factors associated with young Black
      men's information seeking following exposure to a depression disclosure by Scott
      Mescudi. Mescudi is a well-known Black male hip-hop artist who shared his
      depression diagnosis and subsequent treatment plans with his fans in October
      2016. For this study, I surveyed 182 Black males aged 18-34, 1 month after the
      disclosure. Fifty percent sought general information about depression, and 16%
      sought information to ascertain whether they themselves were at risk for
      depression. Feeling emotional distress following the disclosure and having
      current depression symptoms were significantly associated with information
      seeking behaviors. Identification was indirectly related to information seeking
      through emotional distress. Thus, emotional distress appears to play an important
      role in information seeking behaviors following celebrity health disclosures. The
      findings suggest celebrity health disclosures are associated with proactive
      health behaviors among this sample. Implications of the results for theorization
      of celebrity health effects and research on mental health communication with
      young Black men are discussed.

PMID- 30111255
TI  - Upregulation of FoxM1 by MnSOD Overexpression Contributes to Cancer Stem-Like
      Cell Characteristics in the Lung Cancer H460 Cell Line.
AB  - Manganese superoxide dismutase promotes migration and invasion in lung cancer
      cells via upregulation of the transcription factor forkhead box M1. Here, we
      assessed whether upregulation of forkhead box M1 by manganese superoxide
      dismutase overexpression mediates the acquisition of cancer stem-like cell
      characteristics in non-small cell lung cancer H460 cells. The second-generation
      spheroids from H460 cells were used as lung cancer stem-like cells. The levels of
      manganese superoxide dismutase, forkhead box M1, stemness markers (CD133, CD44,
      and ALDH1), and transcription factors (Bmi1, Nanog, and Sox2) were analyzed by
      Western blot. Sphere formation in vitro and carcinogenicity of lung cancer stem
      like cells were evaluated by spheroid formation assay and limited dilution
      xenograft assays. Knockdown or overexpression of manganese superoxide dismutase
      or/and forkhead box M1 by transduction with short hairpin RNA(shRNA) or
      complementary DNA were performed for mechanistic studies. We showed that
      manganese superoxide dismutase and forkhead box M1 amounts as well as the
      expression levels of stemness markers and transcription factors sphere formation
      in vitro, and carcinogenicity of lung cancer stem-like cells were higher than in
      monolayer cells. Lung cancer stem-like cells transduced with manganese superoxide
      dismutase shRNA or FoxM1 shRNA exhibited decreased sphere formation and lower
      amounts of stemness markers and transcription factors. Overexpression of
      manganese superoxide dismutase or FoxM1 in H460 cells resulted in elevated sphere
      formation rates and protein levels of stemness markers and transcription factors.
      Meanwhile, manganese superoxide dismutase knockdown or overexpression accordingly
      altered forkhead box M1 levels. However, forkhead box M1 knockdown or
      overexpression had no effect on manganese superoxide dismutase levels but
      inhibited or promoted lung cancer stem-like cell functions. Interestingly,
      forkhead box M1 overexpression alleviated the inhibitory effects of manganese
      superoxide dismutase knockdown in lung cancer stem-like cells. In a panel of non
      small cell lung cancer cells, including H441, H1299, and H358 cells, compared to
      the respective monolayer counterparts, the expression levels of manganese
      superoxide dismutase and forkhead box M1 were elevated in the corresponding
      spheroids. These findings revealed the role of forkhead box M1 upregulation by
      manganese superoxide dismutase overexpression in maintaining lung cancer stem
      like cell properties. Therefore, inhibition of forkhead box M1 upregulation by
      manganese superoxide dismutase overexpression may represent an effective
      therapeutic strategy for non-small cell lung cancer.

PMID- 30111257
TI  - Evaluation of ghrelin, nesfatin-1 and irisin levels of serum and brain after
      acute or chronic pentylenetetrazole administrations in rats using sodium
      valproate.
AB  - OBJECTIVES: In this study, we aim to reveal the alterations (due to seizure) in
      the serum and brain levels of nesfatin-1, ghrelin and irisin after acute or
      chronic pentylenetetrazole administrations in rats using sodium valproate.
      METHODS: 35 Wistar albino rats were randomly divided into five groups: Control,
      Acute Pentylenetetrazole group (APTZ), Acute Pentylenetetrazole+ Valproate group
      (AVPA), PTZ kindling group (PTZk) and PTZ kindling+ Valproate group (KVPA). Serum
      and brain levels of ghrelin, nesfatin-1 and FNDC5/irisin were determined with
      ELISA. RESULTS: Serum levels of ghrelin were significantly decreased in APTZ and
      PTZk groups compared to the control (p < 0.01). There was a statistically
      significant decrease in brain levels of ghrelin in all groups compared to the
      control group (p < 0.01). There was a statistically significant increase in serum
      nesfatin-1 levels in the APTZ and PTZk groups compared to the control (p < 0.05).
      Serum levels of nesfatin-1 were similar to the control group in both the acute
      and the chronic treatment groups. There was a statistically significant increase
      in brain nesfatin-1 levels of the KVPA group compared to the control (p < 0.05).
      Serum and brain levels of FNDC5/irisin were found significantly increased in
      APTZ, AVPA and PTZk groups compared to the control (p < 0.01). CONCLUSIONS:
      Statistically significant alterations were detected in the serum and brain levels
      of these three peptides in both the PTZ-induced chronic epilepsy model and acute
      seizure model. The results of this study may suggest that the increase in
      FNDC5/irisin and nesfatin-1 levels, and the decrease in ghrelin levels may
      contribute to seizure pathophysiology. However, further studies are needed in
      order to confirm our hypothesis.

PMID- 30111258
TI  - Corrigendum.

PMID- 30111260
TI  - The Effects of Repetitive Information Communication through Multiple Channels on
      Prevention Behavior during the 2015 MERS Outbreak in South Korea.
AB  - Although people nowadays engage in information communication repetitively through
      multiple channels during a public health crisis, the impacts of this
      communication on behavioral outcomes have not been fully examined. The present
      study empirically tests the effects of repetitive information communication
      through multiple channels (RICMC) on risk-prevention behavior. Additionally, the
      mediating roles of knowledge, perceived susceptibility, severity, response
      efficacy, and self-efficacy in the association between RICMC and risk-prevention
      behavior are examined. Analyses of online survey data (N = 1,036) collected
      during the 2015 Middle East respiratory syndrome (MERS) outbreak in South Korea
      revealed that RICMC was positively associated with MERS-prevention behavior.
      Furthermore, this association was mediated by perceived susceptibility, severity,
      and self-efficacy. Although response efficacy and knowledge were not significant
      mediators, RICMC was positively associated with all mediating variables. The
      implications, theoretical contributions, and limitations of this study are
      discussed.

PMID- 30111261
TI  - Reach/Grasp Times with Lateral Reach Obstructions.
AB  - When moving to grasp an object having adjacent obstacles that limit the space
      available for placing the fingers, the time for the reach/grasp is dependent on
      the distance of reaching and the space available for finger placement. Here we
      model the time taken in terms of these variables and develop mathematical models
      for the reach and grasp phases of the task and the location of obstacles. Data
      show that the movement to the target may be made under visual control and that,
      when the obstacles are close to the target object, a visually-controlled movement
      is made that is modeled by a modified form of Fitts' law. The time for the two
      components of the reach/grasp appear to be independent and linearly additive.

PMID- 30111262
TI  - Percutaneous mastoid electrical stimulator alleviates autonomic dysfunction in
      patients with acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Poststroke prognosis is associated with autonomic status.
      The purpose of our study was to determine whether percutaneous mastoid electrical
      stimulator (PMES) can alleviate abnormal heart rate variability (HRV) and improve
      clinical outcome. METHODS: This prospective, randomized, double-blinded, placebo
      controlled study enrolled a total of 140 patients with autonomic dysfunction
      within 3d after acute ischemic stroke. The patients were treated with PMES or
      sham stimulation once daily over a period of 2 weeks. HRV was primarily assessed
      by the fractal dimension (FD) at admission and 2 weeks. All patients were
      followed up for 3 months. The clinical outcome was death and major disability
      (modified Rankin Scale score>= 3) at 3 months after acute ischemic stroke.
      RESULTS: FD of the 2-week treatment period increased in PMES groups. PMES can
      significantly alleviate abnormal HRV. The difference in FD of the 2-week
      treatment period between the PMES and sham groups was significant (1.14 +/- 0.27
      vs. 1.00 +/- 0.23; P = 0.001). In fully adjusted models, PMES was associated with
      reduced 3-month mortality (adjusted odds ratio, 0.32; 95% confidence interval,
      0.11-0.93; P = 0.036). No significant group differences were seen in three major
      disability and composite outcome (P > 0.05). CONCLUSIONS: PMES was a safe,
      effective, and low-cost therapy to alleviate HRV and could significantly reduce
      mortality in the early recovery phase after acute ischemic stroke.

PMID- 30111263
TI  - Illness Narrative: Janice's Story.

PMID- 30111259
TI  - Effectiveness of annual single doses of diethylcarbamazine citrate among
      bancroftian filariasis infected individuals in an endemic area under mass drug
      administration in Brazil.
AB  - The Global Program to Eliminate Lymphatic Filariasis has achieved extraordinary
      success in reducing transmission and preventing morbidity through mass drug
      administration (MDA) to the population at-risk. Brazil is the only currently
      using diethylcarbamazine citrate (DEC) alone for MDA, so an assessment of its
      effectiveness is needed. We report the trends of filarial markers in a cohort of
      175 individuals infected with Wuchereria bancrofti in areas that underwent MDA in
      the city of Olinda, Northeastern Brazil. The prospective study was conducted
      between 2007 and 2012 (corresponding to five annual MDA rounds). The
      quantification of microfilaraemia (QMFF) was assessed by filtration. Circulating
      filarial antigen (CFA) was detected through immunochromatographic point-of-care
      test (POCT-ICT) and Og4C3-ELISA whereas antifilarial antibody titres (IgG4) were
      assessed through Bm14 assay. The CFA and IgG4 titres were measured by Optical
      Density (OD). The main characteristics at baseline, MDA coverage and the trend of
      filarial infection markers during follow up were described. The trend of filarial
      markers in relation to time (years of MDA), sex and age were analysed through
      Generalized Estimating Equations (GEE) models. The models demonstrated a
      significant decrease in all markers during MDA. The probability of remaining
      positive by QMFF and POCT-ICT diminished 70% and 46%, respectively, after each
      MDA round. There was a significant annual drop in CFA (-0.290 OD) and IgG4
      antibodies titres (-0.303 OD). This study provides evidence that MDA with DEC
      alone can be effective in the elimination of LF in Brazil.

PMID- 30111264
TI  - Firefighters' protective jackets: Fit to female form and its effects on
      attributes relevant to thermal comfort.
AB  - Often male and female workers wear protective garments of identical construction
      and style, with females typically wearing small-sized men's garments.
      Consequently, the air spaces under garments worn by male and female wearers can
      substantially differ in size and distribution affecting the physiological comfort
      of firefighters' protective clothing. The present study was designed to
      investigate the effects of varying dimensions and distributions of air spaces in
      the next-to-skin microclimate under firefighters' protective jackets on
      attributes relevant to the thermal comfort of wearer, not only in relation to
      garment construction and fit, but also to human body geometry using 3D body
      scanning. Analysis of 20 scans demonstrated that jackets of the same size and
      construction create larger air spaces under them worn on a female as opposed to
      on a male body form. Both thermal and vapor resistance of clothing were affected
      significantly by the volume of trapped air.

PMID- 30111265
TI  - Cytological diagnosis of microfilaria at unusual sites in clinically unsuspected
      cases: some rare presentations of filariasis.
AB  - Filariasis is a major concern, particularly in endemic regions. The majority of
      patients harbouring the parasite may remain asymptomatic for years. Here, we
      present six patients who were sent for routine cytological examination to rule
      out neoplastic pathology, in whom cytology identified filarial infestation. The
      main purposes of our paper are to highlight the importance of fine needle
      aspiration cytology (FNAC), a cheap and quick investigation to detect the
      microfilaria from tissue swelling and body fluids, and to point out that
      clinicians practising in endemic regions should always consider filarial
      infestation in patients presenting with longstanding swelling.

PMID- 30111266
TI  - Simple and selective analysis of different antibiotics in milk using molecularly
      imprinted polymers: a review.
AB  - The frequent, sometimes illegal, use of antibiotics for therapeutic and
      prophylactic purposes in dairy cattle management may cause residues in milk.
      Because of problems concerning bacterial resistance or allergies in consumers,
      monitoring of residues is required. In spite of the huge development of
      analytical instrumentation during recent years, sample preparation is still a
      bottleneck of the analytical process. In this regard, efforts have been directed
      towards improving selectivity during extraction and clean-up of samples. Compared
      to traditional sorbents, molecularly imprinted polymers (MIPs) are excellent
      materials to provide selectivity for sample pretreatment. This review presents
      the application of MIPs as effective sorbents for separation, clean-up, pre
      concentration and analysis of different antibiotics in milk.

PMID- 30111267
TI  - Malpractice Environment vs Direct Litigation: What Drives Nursing Home Exit?
AB  - An ongoing concern about medical malpractice litigation is that it may induce
      provider exit, potentially affecting consumer welfare. The nursing home sector is
      subject to substantial litigation activity but remains generally understudied in
      terms of the effects of litigation, due perhaps to a paucity of readily available
      data. In this article, we estimate the association between litigation and nursing
      home exit (closure or change in ownership), separating the impact of malpractice
      environment from direct litigation. We use 2 main data sources for this study:
      Westlaw's Adverse Filings database (1997-2005) and Online Survey, Certification
      and Reporting data sets (1997-2005). We use probit models with state and year
      fixed effects to examine the relationship between litigation and the probability
      of nursing home closure or change in ownership with and without adjustment for
      malpractice environment. We examine the relationship on average and also stratify
      by profit status, chain membership, and market competition. We find that direct
      litigation against a nursing home has a nonsignificant effect on the probability
      of closure or change in ownership within the subsequent 2 years. In contrast, the
      broader malpractice environment has a significant effect on change in ownership,
      even for nursing homes that have not been sued, but not on closure. Effects are
      stronger among for-profit and chain facilities and those in more competitive
      markets. A high-risk malpractice environment is associated with change of
      ownership of nursing homes regardless of whether they have been directly sued,
      indicating that it is too blunt an instrument for weeding out low-quality nursing
      homes.

PMID- 30111270
TI  - Palliative Care Leadership.
AB  - Palliative care is one of the newer health specialties and continues to mature.
      While there has been remarkable progression of clinical skills and education,
      there has been a lack of focus on palliative care interdisciplinary leadership or
      development of leadership skills. This article highlights the importance of
      interdisciplinary palliative leadership within the 5 realms of clinical practice,
      research, education, policy/advocacy, and administration. A definition of
      leadership is offered and discussion of successful leadership skills is
      described. A current review of leadership opportunities is provided.

PMID- 30111268
TI  - Four Needles in a Haystack: A Systematic Review Assessing Quality of Health Care
      in Specialty Practice by Practice Type.
AB  - Specialists, who represent 60% of physicians in the United States, are
      consolidating into large group practices, but the degree to which group practice
      type facilitates the delivery of high quality of care in specialty settings is
      unknown. We conducted a systematic literature review to identify the impact of
      group practice type on the quality of care among specialty providers. The search
      resulted in 913 articles, of which only 4 met inclusion criteria. Studies were of
      moderate methodological quality. From the limited evidence available, we
      hypothesize that solo specialists deliver care that is inferior to their peers in
      group practice, whether measured by patient satisfaction ratings or adherence to
      guideline-based care. However, solo specialists and multidisciplinary group
      specialists may be more likely to provide some specialized services compared with
      their single-specialty group peers. Insufficient research compares quality of
      care among different practice types in specialty care. Substantial opportunity
      exists to test the degree to which organizational factors, whether size of
      practice or the mix of providers within the practice, influence quality of care
      in specialty settings.

PMID- 30111269
TI  - Direct Medical Cost of Hospitalization for Acute Stroke in Lebanon: A Prospective
      Incidence-Based Multicenter Cost-of-Illness Study.
AB  - Stroke is a major social and health problem posing heavy burden on national
      economies. We provided detailed financial data on the direct in-hospital cost of
      acute stroke care in Lebanon and evaluated its drivers. This was an
      observational, quantitative, prospective, multicenter, incidence-based, bottom-up
      cost-of-illness study. Medical and billing records of stroke patients admitted to
      8 hospitals in Beirut over 1 year were analyzed. Direct medical costs were
      calculated, and cost drivers were assessed using a multivariable linear
      regression analysis. In total, 203 stroke patients were included (male: 58%; mean
      age: 68.8 +/- 12.9 years). The direct in-hospital cost for all cases was US$1 413
      069 for 2626 days (US$538 per in-hospital day). The average in-hospital cost per
      stroke patient was US$6961 +/- 15 663. Hemorrhagic strokes were the most costly,
      transient ischemic attack being the least costly. Cost drivers were hospital
      length of stay, intensive care unit length of stay, type of stroke, stroke
      severity, modified Rankin Scale, third party payer, surgery, and infectious
      complications. Direct medical cost of acute stroke care represents high financial
      burden to Lebanese health system. Development of targeted public health policies
      and primary prevention activities need to take priority to minimize stroke
      admission in future and to contain this cost.

PMID- 30111271
TI  - Effect of catechins and high-temperature-processed green tea extract on
      scavenging reactive oxygen species and preventing Abeta1-42 fibrils' formation in
      brain microvascular endothelium.
AB  - The present study investigated the effect of high-temperature-processed green tea
      extract (HTP_GTE) and its bioactive components on the reduction of reactive
      oxygen species (ROS) and amyloid-beta (Abeta) protein in human microvascular
      endothelial cells. Compared to Abeta1-42-only treatment, pretreatment of HTP_GTE
      was revealed to effectively inhibit ROS generation (P<0.05). HTP_GTE and
      catechins not only inhibit Abeta1-42 fibril formation but also destabilize
      preformed Abeta1-42 fibrils. The presence of HTP_GTE, Abeta1-42 fibril formation
      was significantly inhibited in a dose-dependent manner at 12.5-100 MUg/ml of
      HTP_GTE, showing 86-56%, respectively. Treatment of various concentrations of
      HTP_GTE and catechins steadily destabilized the preformed Abeta1-42 fibrils for
      24 h in a dose-dependent manner. It was observed that the gallated groups such as
      epigallocatechin gallate, epicatechin gallate, gallocatechin gallate, and
      catechin gallate more effectively disturbed Abeta1-42 fibril formation and
      destabilized the preformed Abeta1-42 fibrils than the non-gallated group. Taken
      together, these findings supported that sterilized green tea could be promising
      natural anti-amyloidogenic agents associated with therapeutic approaches in
      Alzheimer's disease by scavenging ROS generation and Abeta fibril in the brain
      tissue.

PMID- 30111272
TI  - Bellwether states are recognizing new dental specialties.

PMID- 30111273
TI  - The BaleDoneen Method (BDM): A disease-inflammation approach to achieve arterial
      wellness.

PMID- 30111274
TI  - Mental Health Clinician and Community Clergy Collaboration to Address Moral
      Injury in Veterans and the Role of the Veterans Affairs Chaplain.
AB  - Moral injury in veterans with posttraumatic stress disorder includes symptoms of
      guilt and shame, and these symptoms are often not responsive to evidence-based
      mental health treatments. Clergy provide a pathway for relieving the guilt and
      shame. However, there is a long history of mistrust between clergy and mental
      health clinicians and not enough Veterans Health Administration chaplains to meet
      this need. The goal of this study was to gather qualitative interview data from
      relevant stakeholders regarding whether and how Veterans Affairs (VA) mental
      health clinicians and community clergy could collaborate to address moral injury
      issues such as guilt and shame in veterans being treated for posttraumatic stress
      disorder. The stakeholders for this study were veterans, mental health
      clinicians, and clergy. Qualitative data were organized into three domains:
      barriers, facilitators, and intervention suggestions. These data were used to
      develop a new intervention for moral injury that includes a central role for the
      Veterans Affairs chaplain.

PMID- 30111275
TI  - Choosing the number of images and image position when analyzing the UNC Passive
      Aerosol Sampler for occupational exposure assessment.
AB  - The University of North Carolina passive aerosol sampler (UNC sampler) could be
      an alternative when measuring occupational dust exposure, but the time required
      for microscopic imaging of the sampler needs to be reduced to make it more
      attractive. The aims of this study were to (1) characterize the effect on
      precision when reducing imaging, in order to shorten analysis time and (2) assess
      if the position of the images makes a difference. Eighty-eight samplers were
      deployed in different locations of an open pit mine. Sixty images were captured
      for each UNC sampler, covering 51% of its collection surface, using scanning
      electron microscopy. Bootstrapped samples were generated with different image
      combinations, to assess the within-sampler coefficient of variation (CVws) for
      different numbers of images. In addition, the particle concentration relative to
      the distance from the center of the sampler was studied. Reducing the number of
      images collected from the UNC sampler led to up to 8.3% CVws for 10 images when
      calculating respirable fraction. As the overall CV has previously been assessed
      to 36%, the additional contribution becomes minimal, increasing the overall CV to
      37%. The mean concentrations of the images were modestly related to distance from
      the center of the sampler. The CVws changed from 8.26% to 8.13% for 10 images
      when applying rules for the image collection based on distance. Thus, the benefit
      of these rules on the precision is small and the images can therefore be chosen
      at random. In conclusion, reducing the number of images analyzed from 60 to 10,
      corresponding to a reduction of the imaged sampling area from 51% to 8.5%,
      results in a negligible loss in precision for respirable fraction dust
      measurements in occupational environments.

PMID- 30111276
TI  - Generation of renewable mouse intestinal epithelial cell monolayers and organoids
      for functional analyses.
AB  - BACKGROUND: Conditional reprogramming has enabled the development of long-lived,
      normal epithelial cell lines from mice and humans by in vitro culture with ROCK
      inhibitor on a feeder layer. We applied this technology to mouse small intestine
      to create 2D mouse intestinal epithelial monolayers (IEC monolayers) from genetic
      mouse models for functional analysis. RESULTS: IEC monolayers form epithelial
      colonies that proliferate on a feeder cell layer and are able to maintain their
      genotype over long-term passage. IEC monolayers form 3D spheroids in matrigel
      culture and monolayers on transwell inserts making them useful for functional
      analyses. IEC monolayers derived from the Cystic Fibrosis (CF) mouse model CFTR
      ?F508 fail to respond to CFTR activator forskolin in 3D matrigel culture as
      measured by spheroid swelling and transwell monolayer culture via Ussing chamber
      electrophysiology. Tumor IEC monolayers generated from the ApcMin/+ mouse
      intestinal cancer model grow more quickly than wild-type (WT) IEC monolayers both
      on feeders and as spheroids in matrigel culture. CONCLUSIONS: These results
      indicate that generation of IEC monolayers is a useful model system for growing
      large numbers of genotype-specific mouse intestinal epithelial cells that may be
      used in functional studies to examine molecular mechanisms of disease and to
      identify and assess novel therapeutic compounds.

PMID- 30111277
TI  - The association between IGF1 gene rs1520220 polymorphism and cancer
      susceptibility: a meta-analysis based on 12,884 cases and 58,304 controls.
AB  - BACKGROUND: The rs1520220 polymorphism in the insulin-like growth factor 1 (IGF1)
      gene has been reported to affect cancer susceptibly in several studies. However,
      the results of the relevant studies are inconsistent. We conduct a current meta
      analysis to investigate the association between rs1520220 and cancer susceptibly.
      METHODS: Three databases (PubMed, Embase, and Web of Science) were searched for
      studies regarding the relationship between rs1520220 and cancer susceptibly. Odds
      ratios (ORs) and the related 95% confidence intervals (CIs) were employed to
      assess the strength of the associations. A stratified analysis was performed
      according to cancer type, ethnicity, and quality score, and when results were
      obtained from no fewer than two studies, these results were pooled. RESULTS:
      There was no positive association between rs1520220 and overall cancer risk.
      However, the analysis stratified by ethnicity revealed that rs1520220
      significantly increased cancer susceptibility in Asian populations (allele model
      OR = 1.10, 95%Cl = 1.00-1.21, p = 0.040; homozygote model OR = 1.22, 95%Cl = 1.01
      1.47, p = 0.040; dominant model OR = 1.19, 95%Cl = 1.01-1.39, p = 0.033). No
      significantly association was detected in Caucasian populations. The analysis
      stratified by cancer type suggested that rs1520220 was not associated with
      susceptibility to breast cancer. CONCLUSIONS: The results of our meta-analysis
      demonstrate that the role of IGF1 rs1520220 in cancer susceptibility varies by
      ethnicity and cancer type and that rs1520220 increases cancer susceptibility in
      Asian populations.

PMID- 30111278
TI  - New tools to screen wild peanut species for aflatoxin accumulation and genetic
      fingerprinting.
AB  - BACKGROUND: Aflatoxin contamination in peanut seeds is still a serious problem
      for the industry and human health. No stable aflatoxin resistant cultivars have
      yet been produced, and given the narrow genetic background of cultivated peanuts,
      wild species became an important source of genetic diversity. Wild peanut seeds,
      however, are not abundant, thus, an effective method of screening for aflatoxin
      accumulation using minimal seeds is highly desirable. In addition, keeping record
      of genetic fingerprinting of each accession would be very useful for breeding
      programs and for the identification of accessions within germplasm collections.
      RESULTS: In this study, we report a method of screening for aflatoxin
      accumulation that is applicable to the small-size seeds of wild peanuts,
      increases the reliability by testing seed viability, and records the genetic
      fingerprinting of the samples. Aflatoxin levels observed among 20 wild peanut
      species varied from zero to 19000 ng.g-1 and 155 ng.g-1 of aflatoxin B1 and B2,
      respectively. We report the screening of 373 molecular markers, including 288
      novel SSRs, tested on 20 wild peanut species. Multivariate analysis by Neighbor
      Joining, Principal Component Analysis and 3D-Principal Coordinate Analysis using
      134 (36 %) transferable markers, in general grouped the samples according to
      their reported genomes. The best 88 markers, those with high fluorescence, good
      scorability and transferability, are reported with BLAST results. High quality
      markers (total 98) that discriminated genomes are reported. A high quality marker
      with UPIC score 16 (16 out of 20 species discriminated) had significant hits on
      BLAST2GO to a pentatricopeptide-repeat protein, another marker with score 5 had
      hits on UDP-D-apiose synthase, and a third one with score 12 had BLASTn hits on
      La-RP 1B protein. Together, these three markers discriminated all 20 species
      tested. CONCLUSIONS: This study provides a reliable method to screen wild species
      of peanut for aflatoxin resistance using minimal seeds. In addition we report 288
      new SSRs for peanut, and a cost-effective combination of markers sufficient to
      discriminate all 20 species tested. These tools can be used for the systematic
      search of aflatoxin resistant germplasm keeping record of the genetic
      fingerprinting of the accessions tested for breeding purpose.

PMID- 30111279
TI  - Enhancement of Glen Moy x Latham raspberry linkage map using GbS to further
      understand control of developmental processes leading to fruit ripening.
AB  - BACKGROUND: The changing climate is altering timing of key fruit ripening
      processes and increasing the occurrence of fruit defects. To improve our
      understanding of the genetic control of raspberry fruit development an enhanced
      genetic linkage map was developed and used to examine ripening phenotypic data.
      RESULTS: In this study we developed an enhanced genetic linkage map for the
      raspberry cvs. Glen Moy x Latham reference mapping population using genotyping by
      sequencing (GbS). Alignment to a newly sequenced draft reference genome of red
      raspberry, cultivar (cv.) Glen Moy, identified 8019 single nucleotide
      polymorphisms (SNPs). After stringent filtering to take account of read coverage
      over all the progeny individuals, association with a single chromosome,
      heterozygosity and marker regression mapping, 2348 high confidence SNPs were
      retained and integrated with an existing raspberry genetic map. The linkage map
      contained many more SNPs segregating in Latham than in Glen Moy. This caused
      difficulties in quantitative trait loci (QTL) mapping with standard software and
      a novel analysis based on a hidden Markov model was used to improve the mapping.
      QTL mapping using the newly generated dense genetic map not only corroborated
      previously identified genetic locations but also provided additional genetic
      elements controlling fruit ripening in raspberry. CONCLUSION: The high-density
      GbS map located the QTL peaks more precisely than in earlier studies, aligned the
      QTLs with Glen Moy genome scaffolds, narrowed the range of potential candidate
      genes to these regions that can be utilised in other populations or in gene
      expression studies to confirm their role and increased the repertoire of markers
      available to understand the genetic control of fruit ripening traits.

PMID- 30111281
TI  - Development, safety and efficacy of a novel circular-irrigated deca-channel
      mapping and ablation catheter for pulmonary vein isolation.
AB  - BACKGROUND: Pulmonary vein isolation (PVI), a cornerstone for catheter ablation
      of atrial fibrillation (AF), remains a complex and time-consuming procedure.
      Present study introduces a novel, circular-irrigated, deca-channel mapping and
      ablation catheter (CIDMA), describes the in vitro test results on feasibility,
      safety, and acute efficacy of the CIDMA catheter. METHODS: An assembled CIDMA
      catheter was subjected to a number of in vitro tests. With this catheter,
      ablation procedures were first performed in a pig's myocardial strips in vitro to
      determine the effects in unipolar or bipolar configuration. RESULTS: Three
      catheters were assembled. The adjustable circular diameter was changed from
      initial state of 32.41 +/- 0.61 mm into controlled state of 28.61 +/- 0.47 mm (P
      = 0.013). In the plastic model, the push-ability, torque-ability, and kink
      resistance of CIDMA catheter were shown to be satisfactory. In vitro, our
      findings showed that ablation could produce obvious ablation lesions, and
      unipolar ablation (at length, width and depth of 5.0 +/- 1.3, 4.6 +/- 0.7, and
      4.2 +/- 0.6 mm, respectively) was more effective than bipolar (at length, width
      and depth of 2.8 +/- 0.2, 4.2 +/- 0.5, and 2.3 +/- 0.4 mm, respectively) (P <
      0.01). CONCLUSIONS: In vitro, our preliminary data suggest that the CIDMA
      catheter produced optimal ablation lesions, especially in the unipolar ablation
      mode. Future in vivo animal and clinical studies are warranted to test the
      efficacy of this catheter in real-world scenario.

PMID- 30111280
TI  - The ratio of the seroprevalence to the egg-positive prevalence of Schistosoma
      japonicum in China: a meta-analysis.
AB  - BACKGROUND: Schistosomiasis, caused by Schistosoma japonicum, remains one of the
      most important parasitic diseases, and detection of S. japonicum infections in
      humans plays a crucial role in control and treatment. However, comparisons
      between the parasitological and the immunological examinations in the fields of
      China are lacking. Therefore we performed a meta-analysis to compare the
      seroprevalence of Schistosoma japonicum, as determined by IHA or ELISA, with
      coprological prevalence, as determined by Kato-Katz, and estimate the ratio of
      the serological to the egg-positive prevalence in order to evaluate the potential
      threat of egg-negative but worm-positive schistosomiasis. METHODS: Studies
      published up to July 2018 on the parasitological and immunological examinations
      of schistosomiasis in the fields of China were searched in five databases
      including CNKI, WanFang, VIP, PubMed and Web of Science. The ratio of the
      serological to the egg-positive prevalence and its 95%CI for each study were
      calculated, and then point estimates and their 95%CIs of pooled prevalence ratio
      were meta-analyzed. Subgroup meta-analyses were also performed according to
      potential influential factors. RESULTS: A total of 23 articles were included. The
      prevalence ratio varied from 0.57 to 48.83 for IHA to Kato-Katz and ranged from
      0.38 to 13.97 for ELISA to Kato-Katz. The pooled ratio was 4.72 (95%CI: 3.87~
      5.76) for IHA to KK and 4.65 (95%CI: 3.50~ 6.17) for ELISA to KK. Subgroup
      analyses implied that the ratio of the serological to the egg-positive prevalence
      may decrease with the endemic levels. The highest prevalence ratio was observed
      when Kato-Katz was performed with three slides per stool or in hilly and
      mountainous regions. CONCLUSIONS: The worm-determined prevalence by IHA or ELISA
      is 4- to 5-fold higher than the egg-determined prevalence by Kato-Katz, which
      implied Kato-Katz may largely underestimate the prevalence of S. japonicum in
      China. The degree of underestimation was greater when Kato-Katz with three slides
      per stool was carried out, especially in low endemic areas or in hilly and
      mountainous regions. Therefore, more attention should be paid to those egg
      negative but worm-positive patients with the aim of final elimination of S.
      japonicum in China.

PMID- 30111283
TI  - Tailored nurse-led cardiac rehabilitation after myocardial infarction results in
      better risk factor control at one year compared to traditional care: a
      retrospective observational study.
AB  - BACKGROUND: Cardiac rehabilitation improves prognosis after an acute myocardial
      infarction (AMI), however, the optimal method of implementation is unknown. The
      aim of the study was to evaluate the effect of individually-tailored, nurse-led
      cardiac rehabilitation on patient outcomes. METHOD: This single-centre
      retrospective observational study included 217 patients (62 +/- 9 years, 73%
      men). All patients attended cardiac rehabilitation including at least two follow
      up consultations with a nurse. Patients receiving traditional care (n = 105) had
      a routine cardiologist consultation, while for those receiving tailored care (n =
      112) their need for a cardiologist consultation was individually evaluated by the
      nurses. Regression analysis was used to analyse risk factor control and hospital
      readmissions at one year. RESULTS: Patients in the tailored group achieved better
      control of total cholesterol (- 0.1 vs + 0.4 mmol/L change between baseline (time
      of index event) and 12-14-month follow-up, (p = 0.01), LDL cholesterol (- 0.1 vs
      + 0.2 mmol/L, p = 0.02) and systolic blood pressure (- 2.1 vs + 4.3 mmHg, p =
      0.01). Active smokers, at baseline, were more often smoke-free at one-year in the
      tailored group [OR 0.32 (0.1-1.0), p = 0.05]. There was a no significant
      difference in re-admissions during the first year of follow-up. In the tailored
      group 60% of the patients had a cardiologist consultation compared to 98% in the
      traditional group (p < 0.001). The number of nurse visits was the same in both
      groups, while the number of telephone contacts was 38% higher in the tailored
      group (p = 0.02). CONCLUSION: A tailored, nurse-led cardiac rehabilitation
      programme can improve risk factor management in post-AMI patients.

PMID- 30111284
TI  - Analgesic effect of Ropivacaine combined with Dexmedetomidine on brachial plexus
      block.
AB  - BACKGROUND: This randomized controlled study investigated the analgesic effect of
      ropivacaine in combination with dexmedetomidine versus ropivacaine alone on
      brachial plexus block to provide alternative anesthetic means for upper limb
      trauma surgery. METHODS: Totally 114 patients who received upper limb surgeries
      under brachial plexus block anesthesia in our hospital from February 2013 to July
      2015 were enrolled. The patients were randomized to ropivacaine alone (the
      control group) or ropivacaine combined with dexmedetomidine (the combination
      group). The blocking effect on sensory and motor neurons, visual analog scale
      (VAS) score, heart rate (HR), mean arterial pressure (MAP), peripheral capillary
      oxygen saturation (SPO2) and adverse reactions were compared between the two
      groups. RESULTS: The time to onset of sensory and motor nerve blockade was
      significantly shorter in the combination group than in the control group (8.9 min
      vs. 12.4 min for sensation blockade; 7.5 min vs. 12.8 min for motor blockade, P <
      0.05 for both comparisons), and the duration of the blockade was significantly
      longer in the combination group (590.2 min vs. 532.1 min, P < 0.05). There was no
      significant difference in VAS scores between the two groups immediately and 4 h
      after surgery; however, 8, 12 and 24 h after surgery, the VAS scores were all
      significantly lower in the combination group than the control group (2.4 vs. 3.0
      for 8 h; 2.2 vs. 4.2 for 12 h, and 2.1 vs. 5.4 for 24 h, respectively, P < 0.05
      for all comparisons). There was no statistical difference in HR, MAP and SPO2
      between the two groups before anesthesia, but after anesthesia, the MAP and HR
      were significantly lower, and the SPO2 was significantly higher in the
      combination group than the control group (78 vs. 84 for MAP; 72 vs. 79 for HR;
      and 95.1 vs. 88.2 for SPO2, P < 0.05 for all comparisons). The rates of adverse
      reaction was significantly lower in the combination group than the control group
      (3.6 vs. 7.2, P < 0.05). CONCLUSION: The brachial plexus blocking effect of
      ropivacaine combined with dexmedetomidine was superior to that of ropivacaine
      alone, mainly intra-operatively and postoperatively. TRIAL REGISTRATION:
      Analgesic Effect of Ropivacaine Combined with Dexmedetomidine on Brachial Plexus
      Block, ChiCTR1800017372, retrospectively registered on July 26, 2018.

PMID- 30111282
TI  - Gene co-expression network analysis reveals coordinated regulation of three
      characteristic secondary biosynthetic pathways in tea plant (Camellia sinensis).
AB  - BACKGROUND: The leaves of tea plants (Camellia sinensis) are used to produce tea,
      which is one of the most popular beverages consumed worldwide. The nutritional
      value and health benefits of tea are mainly related to three abundant
      characteristic metabolites; catechins, theanine and caffeine. Weighted gene co
      expression network analysis (WGCNA) is a powerful system for investigating
      correlations between genes, identifying modules among highly correlated genes,
      and relating modules to phenotypic traits based on gene expression profiling.
      Currently, relatively little is known about the regulatory mechanisms and
      correlations between these three secondary metabolic pathways at the omics level
      in tea. RESULTS: In this study, levels of the three secondary metabolites in ten
      different tissues of tea plants were determined, 87,319 high-quality unigenes
      were assembled, and 55,607 differentially expressed genes (DEGs) were identified
      by pairwise comparison. The resultant co-expression network included 35 co
      expression modules, of which 20 modules were significantly associated with the
      biosynthesis of catechins, theanine and caffeine. Furthermore, we identified
      several hub genes related to these three metabolic pathways, and analysed their
      regulatory relationships using RNA-Seq data. The results showed that these hub
      genes are regulated by genes involved in all three metabolic pathways, and they
      regulate the biosynthesis of all three metabolites. It is notable that light was
      identified as an important regulator for the biosynthesis of catechins.
      CONCLUSION: Our integrated omics-level WGCNA analysis provides novel insights
      into the potential regulatory mechanisms of catechins, theanine and caffeine
      metabolism, and the identified hub genes provide an important reference for
      further research on the molecular biology of tea plants.

PMID- 30111285
TI  - Fine analysis of a genomic region involved in resistance to Mediterranean corn
      borer.
AB  - BACKGROUND: Sesamia nonagrioides Lefebvere (Mediterranean corn borer, MCB) is the
      main pest of maize in the Mediterranean area. QTL for MCB stalk tunneling and
      grain yield under high MCB infestation had been located at bin 8.03-8.05 (4-21 cM
      and 10-30 cM respectively) in a previous analysis of the EP42 x EP39 RILs mapping
      population. The objective of the present work was to study with higher resolution
      those QTL, and validating and estimating with higher precision their locations
      and effects. To achieve this objective, we developed a set of 38 heterogeneous
      inbred families (HIFs) which were near-homozygous in the genome, except in the
      region under study. The HIFs were evaluated in multiple environments under
      artificial infestation with MCB and genotyped with SNPs. RESULTS: The QTL for
      grain yield under high infestation was confirmed with higher precision and
      improved reliability at 112.6-116.9 Mb. On the contrary, the location of the QTL
      for stalk tunneling was not validated probably due to the fixation of some
      genomic regions during the development of the HIFs. Our study confirmed that the
      co-localization of the QTL for stalk tunneling and grain yield in the previous
      study was due to linked genes, not to pleiotropic effects. So, the QTL for grain
      yield can be used for improving grain yield without undesirable effect on stalk
      tunneling. CONCLUSIONS: The HIF analysis is useful for validating QTL and for
      conducting deeper studies in traits related to corn borer resistance.

PMID- 30111288
TI  - Dental injury in anaesthesia: a tertiary hospital's experience.
AB  - BACKGROUND: Dental injury is a common perioperative complication, but there are
      no country specific data available, especially with the use of supraglottic
      airway devices (SAD). The aims of our study are to report the incidence, risk
      factors, and local practices in the management of perioperative dental injuries
      in Singapore. METHODS: We analyzed data from the departmental database from 2011
      to 2014, noting the anticipated difficulty of airway instrumentation, intubation
      grade, pre-existing dental risk factors, location of dental trauma discovery,
      position of teeth injured and presence of dental referral. The risk factors for
      dental trauma were then identified using logistic regression (between 51 dental
      trauma patients and 55,107 patients without dental trauma). RESULTS: The rate of
      dental injury was 0.092% for general anaesthesia cases. The most significant
      patient risk factor is the presence of pre-existing dental risk factors (OR
      12.55). Anaesthetic risk factors include McGrath MAC usage (OR 2.51) and a
      Cormack and Lehane grade of 3 or more (OR 7.25). Most of the dental injuries were
      discovered in the operating theatre. 7 (13.7%) patients had SAD inserted and only
      23 (45.1%) cases were referred to dental services. CONCLUSION: Videolaryngoscopy
      with the McGrath MAC is associated with an increased likelihood of dental injury.
      This could be either because videolarygoscopes were used when increased risk of
      dental trauma was anticipated, or due to incorrect technique of laryngoscopy.
      Future studies should be done to establish the causality. The management of
      dental injuries could be improved with development of departmental guidelines.

PMID- 30111287
TI  - Genetic analysis of seedling root traits reveals the association of root trait
      with other agronomic traits in maize.
AB  - BACKGROUND: Root systems play important roles in crop growth and stress
      responses. Although genetic mechanism of root traits in maize (Zea mays L.) has
      been investigated in different mapping populations, root traits have rarely been
      utilized in breeding programs. Elucidation of the genetic basis of maize root
      traits and, more importantly, their connection to other agronomic trait(s), such
      as grain yield, may facilitate root trait manipulation and maize germplasm
      improvement. In this study, we analyzed genome-wide genetic loci for maize
      seedling root traits at three time-points after seed germination to identify
      chromosomal regions responsible for both seedling root traits and other agronomic
      traits in a recombinant inbred line (RIL) population (Zong3 * Yu87-1). RESULTS:
      Eight seedling root traits were examined at 4, 9, and 14 days after seed
      germination, and thirty-six putative quantitative trait loci (QTLs), accounting
      for 9.0-23.2% of the phenotypic variation in root traits, were detected. Co
      localization of root trait QTLs was observed at, but not between, the three time
      points. We identified strong or moderate correlations between root traits
      controlled by each co-localized QTL region. Furthermore, we identified an overlap
      in the QTL locations of seedling root traits examined here and six other traits
      reported previously in the same RIL population, including grain yield-related
      traits, plant height-related traits, and traits in relation to stress responses.
      Maize chromosomal bins 1.02-1.03, 1.07, 2.06-2.07, 5.05, 7.02-7.03, 9.04, and
      10.06 were identified QTL hotspots for three or four more traits in addition to
      seedling root traits. CONCLUSIONS: Our identification of co-localization of root
      trait QTLs at, but not between, each of the three time-points suggests that maize
      seedling root traits are regulated by different sets of pleiotropic-effect QTLs
      at different developmental stages. Furthermore, the identification of QTL
      hotspots suggests the genetic association of seedling root traits with several
      other traits and reveals maize chromosomal regions valuable for marker-assisted
      selection to improve root systems and other agronomic traits simultaneously.

PMID- 30111286
TI  - Chemotherapy-induced peripheral neuropathy: evidence from genome-wide association
      studies and replication within multiple myeloma patients.
AB  - BACKGROUND: Based on the possible shared mechanisms of chemotherapy-induced
      peripheral neuropathy (CIPN) for different drugs, we aimed to aggregate results
      of all previously published genome-wide association studies (GWAS) on CIPN, and
      to replicate them within a cohort of multiple myeloma (MM) patients. METHODS:
      Following a systematic literature search, data for CIPN associated single
      nucleotide polymorphisms (SNPs) with P-values< 10- 5 were extracted; these
      associations were investigated within a cohort of 983 German MM patients treated
      with bortezomib, thalidomide or vincristine. Cases were subjects that developed
      CIPN grade 2-4 while controls developed no or sub-clinical CIPN. Logistic
      regression with additive model was used. RESULTS: In total, 9 GWASs were
      identified from the literature on CIPN caused by different drugs (4 paclitaxel, 2
      bortezomib, 1 vincristine, 1 docetaxel, and 1 oxaliplatin). Data were extracted
      for 526 SNPs in 109 loci. One hundred fourty-eight patients in our study
      population were CIPN cases (102/646 bortezomib, 17/63 thalidomide and 29/274
      vincristine). In total, 13 SNPs in 9 loci were replicated in our population (p
      value< 0.05). The four smallest P-values relevant to the nerve function were
      0.0006 for rs8014839 (close to the FBXO33 gene), 0.004 for rs4618330 (close to
      the INTU gene), 0.006 for rs1903216 (close to the BCL6 gene) and 0.03 for
      rs4687753 (close to the IL17RB gene). CONCLUSIONS: Replicated SNPs provide clues
      of the molecular mechanism of CIPN and can be strong candidates for further
      research aiming to predict the risk of CIPN in clinical practice, particularly
      rs8014839, rs4618330, rs1903216, and rs4687753, which showed relevance to the
      function of nervous system.

PMID- 30111289
TI  - Safety and efficacy of ultrathin strut biodegradable polymer sirolimus-eluting
      stent versus durable polymer drug-eluting stents: a meta-analysis of randomized
      trials.
AB  - BACKGROUND: The Orsiro biodegradable polymer sirolimus-eluting stent (O-SES) is a
      new-generation biodegradable polymer drug-eluting stent with the thinnest strut
      thickness to date developed to improve the percutaneous treatment of patients
      with coronary artery disease. We perform a meta-analysis of randomized clinical
      trials (RCTs) comparing the efficacy and safety of an ultra-thin, Orsiro
      biodegradable polymer sirolimus-eluting stent (O-SES) compared with durable
      polymer drug-eluting stents (DP-DESs). METHODS: Medline, Embase, and CENTRAL
      databases were searched for randomized controlled trials comparing the safety and
      efficacy of O-SES versus DP-DES. Paired reviewers independently screened
      citations, assessed risk of bias of included studies, and extracted data. We used
      the Mantel-Haenszel method to calculate risk ratio (RR) by means of a random
      effects model. RESULTS: Six RCTs with a total of 6949 patients were selected. All
      included trials were rated as low risk of bias. The O-SES significantly reduced
      the risk of myocardial infarction (RR 0.78, 95% confidence interval [CI] 0.62
      0.98; I2 = 0%; 10 fewer per 1000 [from 1 fewer to 18 fewer]; high quality)
      compared with the DP-DES. There was no significant difference between O-SES and
      DP-DES in the prevention of stent thrombosis (RR: 0.75; 95% CI: 0.52-1.08),
      cardiac death (RR: 0.93; 95% CI: 0.63-1.36), target lesion revascularization (RR
      1.10, 95% CI 0.86-1.42) and target vessel revascularization (RR 0.97, 95% CI 0.78
      1.21). CONCLUSION: Among patients undergoing percutaneous coronary intervention,
      O-SES resulted in significantly lower rates of myocardial infarction than DP-DES
      and had a trend toward reduction in stent thrombosis.

PMID- 30111290
TI  - Development of a quadruple qRT-PCR assay for simultaneous identification of
      highly and low pathogenic H7N9 avian influenza viruses and characterization
      against oseltamivir resistance.
AB  - BACKGROUND: During the fifth wave of human H7N9 infections, a novel highly
      pathogenic (HP) H7N9 variant emerged with an insertion of multiple basic amino
      acids in the HA cleavage site. Moreover, a neuraminidase inhibitor (NAI)
      resistance (R292K in NA) mutation was found in H7N9 isolates from humans, poultry
      and the environment. In this study, we set out to develop and validate a
      multiplex quantitative reverse transcript polymerase chain reaction (qRT-PCR) to
      simultaneously detect the presence of H7N9 and further identify the HP and NAI
      resistance mutations. METHODS: A quadruple qRT-PCR to simultaneously detect the
      presence of H7N9 and further identify the HP and NAI-resistance mutations was
      designed based on the analyses of the HA and NA genes of H7N9. This assay was
      further tested for specificity and sensitivity, and validated using clinical
      samples. RESULTS: The assay was highly specific and able to detect low pathogenic
      (LP)- or HP-H7N9 with/without the NAI-resistance mutation. The detection limit of
      the assay was determined to be 50 genome-equivalent copies and 2.8 * 10- 3 50%
      tissue culture infectious doses (TCID50) of live H7N9 per reaction. Clinical
      validation was confirmed by commercial kits and Sanger sequencing with ten
      clinical samples. CONCLUSIONS: We developed and validated a rapid, single
      reaction, one-step, quadruple real-time qRT-PCR to simultaneously detect the
      presence of H7N9 and further identify the HP- and NAI-resistance strains with
      excellent performance in specificity and sensitivity. This assay could be used to
      monitor the evolution of H7N9 viruses in the laboratory, field and the clinic for
      early-warning and the prevention of H7N9 infections.

PMID- 30111291
TI  - Biopsychosocial predictors and trajectories of work participation after
      transdiagnostic occupational rehabilitation of participants with mental and
      somatic disorders: a cohort study.
AB  - BACKGROUND: Group-based transdiagnostic occupational rehabilitation programs
      including participants with mental and somatic disorders have emerged in clinical
      practice. Knowledge is sparse on subsequent participation in competitive work.
      This study aimed to investigate trajectories for (re)entry to work for predefined
      subgroups in a diagnostically heterogeneous sample of sick-listed participants
      after completing occupational rehabilitation. METHODS: A cohort of 212
      participants aged 18-69 on long-term sick leave (> 8 weeks) with chronic pain,
      chronic fatigue and/or common mental disorders was followed for one year after
      completing a 31/2-week rehabilitation intervention based on Acceptance and
      Commitment Therapy. Self-reported, clinical and registry data were used to study
      the associations between predefined biopsychosocial predictors and trajectories
      for (re)entry to competitive work (>= 1 day per week on average over 8 weeks).
      Generalized estimating equations analysis was used to investigate trajectories.
      RESULTS: For all biopsychosocial subgroups (re)entry to work increased over time.
      Baseline employment, partial sick leave and higher expectation of return to work
      (RTW) predicted higher probability of having (re)entered work at any given time
      after discharge. The odds of increasing reentry over time (statistical
      interaction with time) was weaker for the group receiving the benefit work
      assessment allowance compared with those receiving sickness benefit (OR = 0.92, p
      = 0.048) or for those on partial sick leave compared with full sick leave (OR
      0.77, p < 0.001), but higher for those who at baseline had reported having a poor
      economy versus not (OR 1.16, p = 0.010) or reduced emotional functioning compared
      with not (OR 1.11, p = 0.012). Health factors did not differentiate substantially
      between trajectories. CONCLUSIONS: Work participation after completing a
      transdiagnostic occupational rehabilitation intervention was investigated.
      Individual and system factors related to work differentiated trajectories for
      (re)entry to work, while individual health factors did not. Having a mental
      disorder did not indicate a worse prognosis for (re)entry to work following the
      intervention. Future trials within occupational rehabilitation are recommended to
      pivot their focus to work-related factors, and to lesser extent target diagnostic
      group.

PMID- 30111294
TI  - Minimal effective weight-based dosing of ondansetron to reduce hypotension in
      cesarean section under spinal anesthesia: a randomized controlled superiority
      trial.
AB  - BACKGROUND: The weight-based dosing of ondansetron to reduce hypotension has
      never been investigated. The aim of this study is to determine the optimal dose
      of ondansetron required based on the patient's weight to reduce hypotension
      following spinal anesthesia for cesarean section. METHODS: In this prospective,
      triple-blinded, parallel group, randomized controlled trial, a total of 228
      pregnant women were randomized to receive either normal saline (group NS) or
      ondansetron 0.05 mg/kg (group O1) or ondansetron 0.1 mg/kg (group O2)
      intravenously 5 min before induction of spinal anesthesia. The incidence of
      hypotension, mean arterial pressure, heart rate, vasopressor requirements, and
      blood loss between the three groups were compared. Maternal and neonatal
      complications were also assessed. Changes in blood pressure and heart rate were
      compared using the generalized estimating equations method. RESULTS: Thirteen
      patients were excluded from the analysis because of no intervention (n = 12) and
      protocol violation (n = 1). Two hundred and fifteen patients remained for the
      intention-to-treat analysis. The incidence of hypotension in groups NS (n = 72),
      O1 (n = 71), and O2 (n = 72) were 81.9%, 84.5%, and 73.6%, respectively (P =
      0.23). The episodes of hypotension before delivery (first 14 min after spinal
      anesthesia) were significantly higher in group O1 compared to NS (5 vs 2, P =
      0.02). The overall heart rates throughout the operations were not different among
      the three groups. The ephedrine requirements and amount of blood loss were also
      similar among the three groups. The metoclopramide requirement was significantly
      lower in group O2 compared to group NS (2.8% vs 16.7%, P = 0.01). There were no
      serious adverse events in terms of maternal or neonatal complications.
      CONCLUSIONS: Ondansetron 0.05 mg/kg or 0.1 mg/kg administered before spinal
      anesthesia did not reduce the incidence of hypotension in this study. TRIAL
      REGISTRATION: Thai Clinical Trials Registry, TCTR 20160323001 , 22 March 2016.

PMID- 30111293
TI  - Plasma levels of soluble VEGF receptor isoforms, circulating pterins and VEGF
      system SNPs as prognostic biomarkers in patients with acute coronary syndromes.
AB  - BACKGROUND: Development of collateral circulation in coronary artery disease is
      cardio-protective. A key process in forming new blood vessels is attraction to
      occluded arteries of monocytes with their subsequent activation as macrophages.
      In patients from a prospectively recruited post-acute coronary syndromes cohort
      we investigated the prognostic performance of three products of activated
      macrophages, soluble vascular endothelial growth factor (VEGF) receptors (sFlt-1
      and sKDR) and pterins, alongside genetic variants in VEGF receptor genes, VEGFR-1
      and VEGFR-2. METHODS: Baseline levels of sFlt-1 (VEGFR1), sKDR (VEGFR2) and
      pterins were measured in plasma samples from subgroups (n = 513; 211; 144,
      respectively) of the Coronary Disease Cohort Study (CDCS, n = 2067). DNA samples
      from the cohort were genotyped for polymorphisms from the VEGFR-1 gene SNPs
      (rs748252 n = 2027, rs9513070 n = 2048) and VEGFR-2 gene SNPs (rs2071559 n =
      2050, rs2305948 n = 2066, rs1870377 n = 2042). RESULTS: At baseline, levels of
      sFlt-1 were significantly correlated with age, alcohol consumption, NTproBNP, BNP
      and other covariates relevant to cardiovascular pathophysiology. Total neopterin
      levels were associated with alcohol consumption at baseline. 7,8 dihydroneopterin
      was associated with BMI. The A allele of VEGFR-2 variant rs1870377 was associated
      with higher plasma sFlt-1 and lower levels of sKDR at baseline. Baseline plasma
      sFlt-1 was univariately associated with all cause mortality with (p < 0.001) and
      in a Cox's proportional hazards regression model sFlt-1 and pterins were both
      associated with mortality independent of established predictors (p < 0.027).
      CONCLUSIONS: sFlt-1 and pterins may have potential as prognostic biomarkers in
      acute coronary syndromes patients. Genetic markers from VEGF system genes warrant
      further investigation as markers of levels of VEGF system components in these
      patients. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry.
      ACTRN12605000431628 . 16 September 2005, Retrospectively registered.

PMID- 30111292
TI  - Population genomics and morphometric assignment of western honey bees (Apis
      mellifera L.) in the Republic of South Africa.
AB  - BACKGROUNDS: Apis mellifera scutellata and A.m. capensis (the Cape honey bee) are
      western honey bee subspecies indigenous to the Republic of South Africa (RSA).
      Both bees are important for biological and economic reasons. First, A.m.
      scutellata is the invasive "African honey bee" of the Americas and exhibits a
      number of traits that beekeepers consider undesirable. They swarm excessively,
      are prone to absconding (vacating the nest entirely), usurp other honey bee
      colonies, and exhibit heightened defensiveness. Second, Cape honey bees are
      socially parasitic bees; the workers can reproduce thelytokously. Both bees are
      indistinguishable visually. Therefore, we employed Genotyping-by-Sequencing
      (GBS), wing geometry and standard morphometric approaches to assess the genetic
      diversity and population structure of these bees to search for diagnostic markers
      that can be employed to distinguish between the two subspecies. RESULTS: Apis
      mellifera scutellata possessed the highest mean number of polymorphic SNPs (among
      2449 informative SNPs) with minor allele frequencies > 0.05 (Np = 88%). The RSA
      honey bees generated a high level of expected heterozygosity (Hexp = 0.24). The
      mean genetic differentiation (FST; 6.5%) among the RSA honey bees revealed that
      approximately 93% of the genetic variation was accounted for within individuals
      of these subspecies. Two genetically distinct clusters (K = 2) corresponding to
      both subspecies were detected by Model-based Bayesian clustering and supported by
      Principal Coordinates Analysis (PCoA) inferences. Selected highly divergent loci
      (n = 83) further reinforced a distinctive clustering of two subspecies across
      geographical origins, accounting for approximately 83% of the total variation in
      the PCoA plot. The significant correlation of allele frequencies at divergent
      loci with environmental variables suggested that these populations are adapted to
      local conditions. Only 17 of 48 wing geometry and standard morphometric
      parameters were useful for clustering A.m. capensis, A.m. scutellata, and hybrid
      individuals. CONCLUSIONS: We produced a minimal set of 83 SNP loci and 17 wing
      geometry and standard morphometric parameters useful for identifying the two RSA
      honey bee subspecies by genotype and phenotype. We found that genes involved in
      neurology/behavior and development/growth are the most prominent heritable traits
      evolved in the functional evolution of honey bee populations in RSA. These
      findings provide a starting point for understanding the functional basis of
      morphological differentiations and ecological adaptations of the two honey bee
      subspecies in RSA.

PMID- 30111295
TI  - First case report of malignant peritoneal mesothelioma and oral verrucous
      carcinoma in a patient with a germline PTEN mutation: a combination of extremely
      rare diseases with probable further implications.
AB  - BACKGROUND: The PTEN-hamartoma-tumor-syndrome (PHTS) is caused by germline
      mutations in Phosphatase and Tensin homolog (PTEN) and predisposes to the
      development of several typical malignancies. Whereas PTEN mutations have been
      implicated in the occurrence of malignant mesotheliomas, the genetic landscape of
      verrucous carcinomas (VC) is largely uncharted. Both VC and malignant peritoneal
      mesotheliomas (MPM) are exceedingly rare and a potential link between these
      malignancies and PHTS has never been reported. CASE PRESENTATION: We here
      describe the clinical course of a PHTS patient who, in addition to a typical
      thyroid carcinoma at the age of 36 years, developed a highly-differentiated oral
      VC and an epithelioid MPM six years later. The patient with a history of
      occupational asbestos exposure underwent cytoreductive surgery and hyperthermic
      intraperitoneal chemotherapy for MPM. The clinical diagnosis of PHTS was
      consequently corroborated by a germline PTEN deletion. Sequencing of tumor tissue
      revealed a second hit in PTEN in the thyroid carcinoma and VC, confirmed by a
      PTEN loss and activation of the PI3K/AKT pathway in immunohistochemistry.
      Furthermore, additional somatic mutations in the thyroid carcinoma as well as in
      the VC were detected, whereas the genetics of MPM remained unrevealing.
      DISCUSSION AND CONCLUSIONS: We here report the very unusual clinical course of a
      patient with rare tumors that have a germline mutation first hit in PTEN in
      common. Since this patient was exposed to asbestos and current evidence suggests
      molecular mechanisms that might render PHTS patients particularly susceptible to
      mesothelioma, we strongly recommend PHTS patients to avoid even minimal exposure.

PMID- 30111296
TI  - Targeting colorectal cancer cell metabolism through development of cisplatin and
      metformin nano-cubosomes.
AB  - BACKGROUND: Colorectal cancer (CRC) remains a leading cause of death worldwide.
      Utilizing cisplatin in CRC is correlated with severe adverse effects and drug
      resistance. Combined anticancer drug-treatment, along with, their enhanced
      delivery, can effectively kill cancer through multiple pathways. Nano-cubosomes
      are emerging as nanocarriers for anticancer therapies, hence, we constructed nano
      cubosomes bearing cisplatin and cisplatin-metformin combination for investigation
      on HCT-116 cells. METHODS: Nano-cubosomes bearing either cisplatin alone or
      cisplatin-metformin combination were formulated using emulsification technique.
      The loaded nano-cubosomes were characterized in vitro and the optimized
      formulation was selected. Their cytotoxic effects were investigated by
      Sulphorhodamine-B (SRB) assay. The AMPK/mTOR metabolic pathway as well as the
      Akt/mTOR pathway were analyzed using ELISA technique. Colorimetry was used in
      NADPH oxidase, LDH and caspase-3 activity determination. RESULTS: nano-cubosomal
      formulations exhibited superior cytotoxic effect compared to unformulated
      cisplatin. This cytotoxic effect was profound upon incorporation of metformin, an
      indirect mTOR inhibitor, in cisplatin nano-cubosomes. The induced CRC cell
      apoptosis was through inhibition of several metabolic pathways, namely, AMPK/mTOR
      and Akt/mTOR. Drug-loaded nano-cubosomes ensued depletion in glucose and energy
      levels that led to AMPK activation and thus mTOR inhibition. mTOR was
      additionally inhibited via suppression of p-Akt (Ser473) levels after nano
      cubosomal treatment. Moreover, drug-loaded nano-cubosomes produced a notable
      escalation in ROS levels, evident as an increase in NADPH oxidase, inhibition of
      LDH and a consequential upsurge in caspase-3. CONCLUSION: These results
      demonstrated the influence exerted by cisplatin-loaded nano-cubosomes on CRC cell
      survival and enhancement of their cytotoxicity upon metformin addition.

PMID- 30111297
TI  - Hypoxia promotes acquisition of aggressive phenotypes in human malignant
      mesothelioma.
AB  - BACKGROUND: Hypoxia is a hallmark of the solid tumor microenvironment and is
      associated with poor outcomes in cancer patients. The present study was performed
      to investigate mechanisms underlying the hypoxia-induced phenotypic changes using
      human malignant mesothelioma (HMM) cells. METHODS: Hypoxic conditions were
      achieved by incubating HMM cells in the air chamber. The effect of hypoxia on
      phenotype changes in HMM cells was investigated by performing in vitro
      clonogenicity, drug resistance, migration, and invasion assays. Signaling
      pathways and molecules involved in the more aggressive behaviors of HMM cells
      under hypoxia were investigated. A two-tailed unpaired Student's t-test or one
      way ANOVA with Bonferroni post-test correction was used in this study. RESULTS:
      Hypoxic conditions upregulated hypoxia-inducible factor 1 alpha (HIF-1alpha) and
      HIF-2alpha in parallel with the upregulation of its target, Glut-1, in HMM cells.
      In vitro clonogenicity of HMM cells was significantly increased in hypoxic
      conditions, but the proliferation of cells at a high density in hypoxia was lower
      than that in normoxic conditions. The expression levels of HIF-2alpha and Oct4
      were increased in hypoxic HMM cells. The percentage of cells with high CD44
      expression was significantly higher in HMM cells cultured in hypoxia than those
      cultured in normoxia. Hypoxia significantly enhanced the resistance of HMM cells
      to cisplatin, which occurred through cytoprotection against cisplatin-induced
      apoptosis. While cisplatin treatment decreased the ratio of Bcl-2 to Bax in
      normoxic condition, hypoxia conversely increased the ratio in HMM cells treated
      with cisplatin. Hypoxia increased the mobility and invasiveness of HMM cells.
      Epithelial to mesenchymal transition was promoted, which was indicated by the
      repression of E-cadherin and the concomitant increase of vimentin in HMM cells.
      CONCLUSIONS: The data illustrated that hypoxic conditions augmented the
      aggressive phenotypes of HMM cells at the biological and molecular levels. The
      present study provides valuable background information beginning to understand
      aggressiveness of HMM in tumor microenvironments, suggesting that a control
      measure for tumor hypoxia may be an effective therapeutic strategy to reduce the
      aggressiveness of cancer cells in HMM patients.

PMID- 30111298
TI  - Using motivational techniques to reduce cardiometabolic risk factors in long term
      psychiatric inpatients: a naturalistic interventional study.
AB  - BACKGROUND: People with severe mental illness have markedly reduced life
      expectancy; cardiometabolic disease is a major cause. Psychiatric hospital
      inpatients have elevated levels of cardiometabolic risk factors and are to a high
      degree dependent of the routines and facilities of the institutions. Studies of
      lifestyle interventions to reduce cardiometabolic risk in psychiatric inpatients
      are few. The current study aimed at assessing the feasibility and effects of a
      lifestyle intervention including Motivational Interviewing (MI) on physical
      activity levels, cardiometabolic risk status and mental health status in
      psychotic disorder inpatients. METHODS: Prospective naturalistic intervention
      study of 83 patients at long term inpatient psychosis treatment wards in South
      Eastern Norway. Patients were assessed 3-6 months prior to, at start and 6 months
      after a life-style intervention program including training of staff in MI, simple
      changes in routines and improvements of facilities for physical exercise.
      Assessments were done by clinical staff and included level of physical activity,
      motivation, life satisfaction, symptom levels (MADRS, AES-C, PANSS, and GAF) as
      well as anthropometric and biochemical markers of cardiometabolic risk. A mixed
      model was applied to analyze change over time. RESULTS: A total of 88% of
      patients received MI interventions, with a mean of 2.5 MI interventions per week
      per patient. The physical activity level was not increased, but activity level
      was positively associated with motivation and negatively associated with positive
      symptoms. Triglyceride levels and number of smokers were significantly reduced
      and a significant decrease in symptom levels was observed. CONCLUSIONS: The
      current results suggest that a simple, low cost life-style intervention program
      focusing on motivational change is feasible and may reduce symptoms and improve
      lifestyle habits in psychosis patients in long term treatment facilities. Similar
      programs may easily be implemented in other psychiatric hospitals. TRIAL
      REGISTRATION: ClinicalTrials.gov . NCT03528278 , date of registration: 05/16/2018
      (retrospectively registered).

PMID- 30111299
TI  - Palliative care in intensive care units: why, where, what, who, when, how.
AB  - Palliative care is patient and family-centered care that optimizes quality of
      life by anticipating, preventing, and treating suffering when "curative"
      therapies are futile. In the Intensive Care Unit (ICU), critically ill patients
      receive life-sustaining therapies with the goal of restoring or maintaining organ
      function. Palliative Care in the ICU is a widely discussed topic and it is
      increasingly applied in clinics. It encompasses symptoms control and end-of-life
      management, communication with relatives and setting goals of care ensuring
      dignity in death and decision-making power. However, effective application of
      Palliative Care in ICU presupposes specific knowledge and training which
      anesthesiologists and critical care physicians may lack. Moreover, logistic
      issues such protocols for patients' selection, application models and triggers
      for consultation of external experts are still matter of debate.The aim of this
      review is to provide the anesthesiologists and intensivists an overview of the
      aims, current evidence and practical advices about the application of palliative
      care in ICU.

PMID- 30111300
TI  - A systematic review and meta-analysis of epidemiology of depression in people
      living with HIV in east Africa.
AB  - BACKGROUND: Depression is the most prevalent psychiatric disorder among people
      living with HIV (PLWHIV) and is associated with poor quality of life, additional
      comorbidities, disability, unemployment, poorer therapeutic outcomes and risky
      behaviors. The present systematic review and meta-analysis aims to systematically
      summarize empirical evidence and to formulate recommendations for future
      research. METHODS: We searched PubMed, EMBASE, SCOPUS, and relevant literature
      for possible studies to include. A qualitative and quantitative analysis was
      undertaken for this systematic review. Subgroup and sensitivity analysis were
      performed. Cochran's Q- and the I2 test were used to assess heterogeneity. The
      presence of publication bias was evaluated by using Egger's test and visual
      inspection of the symmetry in funnel plots. RESULTS: Of 283 titles initially
      identified, 81 abstracts were eligible for review. Of these, 46 articles
      qualified for full text review and 19 were retained. In our meta-analysis the
      pooled prevalence of depression in PLWHIV was 38% (95% CI 29.30-47.54). The
      pooled prevalence estimates of depression was 49.79% in Ethiopia and 30.88% in
      Uganda. In addition, the prevalence of depression was 12.40% and 46% as measured
      by diagnostic and screening instrument respectively. Our qualitative synthesis
      showed that factors such as having opportunistic infection, perceived stigma,
      negative life event, WHO clinical staging of disease, hospitalization in the past
      one month, stressful life events, food insecurity, self-efficacy, missed
      frequency of clinic visit, frequency of follow-up, older age, low income, urban
      residence and being government employee were strongly and significantly
      associated with depression in PLWHIV in east Africa. CONCLUSION: The pooled
      prevalence estimates of prevalence of depression in PLWHIV was 38%. The
      prevalence estimates of depression in PLWHIV in Ethiopia was significantly higher
      than Uganda. In addition the prevalence of depression was significantly higher in
      studies conducted by screening than diagnostic instrument. Routine screening and
      integrated management of depression into the existing HIV care services is
      warranted. Validation and use of standard instrument to assess depression in
      PLWHIV is needed. Moreover, longitudinal and community based studies focusing on
      incidence and determinates of depression in PLWHIV are recommended.

PMID- 30111302
TI  - A systematic review of co-responder models of police mental health 'street'
      triage.
AB  - BACKGROUND: Police mental health street triage is an increasingly common
      intervention when dealing with police incidents in which there is a suspected
      mental health component. We conducted a systematic review of street triage
      interventions with three aims. First, to identify papers reporting on models of
      co-response police mental health street triage. Second, to identify the
      characteristics of service users who come in to contact with these triage
      services. Third, to evaluate the effectiveness of co-response triage services.
      METHODS: We conducted a systematic review. We searched the following databases:
      Ovid MEDLINE, Embase, PsycINFO, EBSCO CINAHL, Scopus, Thompson Reuters Web of
      Science Core Collection, The Cochrane Library, ProQuest National Criminal Justice
      Reference Service Abstracts, ProQuest Dissertations & Theses, EThoS, and
      OpenGrey. We searched reference and citation lists. We also searched for other
      grey literature through Google, screening the first 100 PDFs of each of our
      search terms. We performed a narrative synthesis of our results. RESULTS: Our
      search identified 11,553 studies. After screening, 26 were eligible. Over two
      thirds (69%) had been published within the last 3 years. We did not identify any
      randomised control trials. Results indicated that street triage might reduce the
      number of people taken to a place of safety under S136 of the Mental Health Act
      where that power exists, or reduce the use of police custody in other
      jurisdictions. CONCLUSIONS: There remains a lack of evidence to evaluate the
      effectiveness of street triage and the characteristics, experience, and outcomes
      of service users. There is also wide variation in the implementation of the co
      response model, with differences in hours of operation, staffing, and incident
      response.

PMID- 30111301
TI  - BMScan: using whole genome similarity to rapidly and accurately identify
      bacterial meningitis causing species.
AB  - BACKGROUND: Bacterial meningitis is a life-threatening infection that remains a
      public health concern. Bacterial meningitis is commonly caused by the following
      species: Neisseria meningitidis, Streptococcus pneumoniae, Listeria
      monocytogenes, Haemophilus influenzae and Escherichia coli. Here, we describe
      BMScan (Bacterial Meningitis Scan), a whole-genome analysis tool for the species
      identification of bacterial meningitis-causing and closely-related pathogens, an
      essential step for case management and disease surveillance. BMScan relies on a
      reference collection that contains genomes for 17 focal species to scan against
      to identify a given species. We established this reference collection by
      supplementing publically available genomes from RefSeq with genomes from the
      isolate collections of the Centers for Disease Control Bacterial Meningitis
      Laboratory and the Minnesota Department of Health Public Health Laboratory, and
      then filtered them down to a representative set of genomes which capture the
      diversity for each species. Using this reference collection, we evaluated two
      genomic comparison algorithms, Mash and Average Nucleotide Identity, for their
      ability to accurately and rapidly identify our focal species. RESULTS: We found
      that the results of Mash were strongly correlated with the results of ANI for
      species identification, while providing a significant reduction in run-time. This
      drastic difference in run-time enabled the rapid scanning of large reference
      genome collections, which, when combined with species-specific threshold values,
      facilitated the development of BMScan. Using a validation set of 15,503 genomes
      of our species of interest, BMScan accurately identified 99.97% of the species
      within 16 min 47 s. CONCLUSIONS: Identification of the bacterial meningitis
      pathogenic species is a critical step for case confirmation and further strain
      characterization. BMScan employs species-specific thresholds for previously
      validated, genome-wide similarity statistics compiled from a curated reference
      genome collection to rapidly and accurately identify the species of
      uncharacterized bacterial meningitis pathogens and closely related pathogens.
      BMScan will facilitate the transition in public health laboratories from
      traditional phenotypic detection methods to whole genome sequencing based methods
      for species identification.

PMID- 30111303
TI  - Comparison of logistic regression with machine learning methods for the
      prediction of fetal growth abnormalities: a retrospective cohort study.
AB  - BACKGROUND: While there is increasing interest in identifying pregnancies at risk
      for adverse outcome, existing prediction models have not adequately assessed
      population-based risks, and have been based on conventional regression methods.
      The objective of the current study was to identify predictors of fetal growth
      abnormalities using logistic regression and machine learning methods, and compare
      diagnostic properties in a population-based sample of infants. METHODS: Data for
      30,705 singleton infants born between 2009 and 2014 to mothers resident in Nova
      Scotia, Canada was obtained from the Nova Scotia Atlee Perinatal Database.
      Primary outcomes were small (SGA) and large for gestational age (LGA). Maternal
      characteristics pre-pregnancy and at 26 weeks were studied as predictors.
      Logistic regression and select machine learning methods were used to build the
      models, stratified by parity. Area under the curve was used to compare the
      models; relative importance of predictors was compared qualitatively. RESULTS:
      7.9% and 13.5% of infants were SGA and LGA, respectively; 48.6% of births were to
      primiparous women and 51.4% were to multiparous women. Prediction of SGA and LGA
      was poor to fair (area under the curve 60-75%) and improved with increasing
      parity and pregnancy information. Smoking, previous low birthweight infant, and
      gestational weight gain were important predictors for SGA; pre-pregnancy body
      mass index, gestational weight gain, and previous macrosomic infant were the
      strongest predictors for LGA. CONCLUSIONS: The machine learning methods used in
      this study did not offer any advantage over logistic regression in the prediction
      of fetal growth abnormalities. Prediction accuracy for SGA and LGA based on
      maternal information is poor for primiparous women and fair for multiparous
      women.

PMID- 30111305
TI  - Comparison of crowd-sourced, electronic health records based, and traditional
      health-care based influenza-tracking systems at multiple spatial resolutions in
      the United States of America.
AB  - BACKGROUND: Influenza causes an estimated 3000 to 50,000 deaths per year in the
      United States of America (US). Timely and representative data can help local,
      state, and national public health officials monitor and respond to outbreaks of
      seasonal influenza. Data from cloud-based electronic health records (EHR) and
      crowd-sourced influenza surveillance systems have the potential to provide
      complementary, near real-time estimates of influenza activity. The objectives of
      this paper are to compare two novel influenza-tracking systems with three
      traditional healthcare-based influenza surveillance systems at four spatial
      resolutions: national, regional, state, and city, and to determine the minimum
      number of participants in these systems required to produce influenza activity
      estimates that resemble the historical trends recorded by traditional
      surveillance systems. METHODS: We compared influenza activity estimates from five
      influenza surveillance systems: 1) patient visits for influenza-like illness
      (ILI) from the US Outpatient ILI Surveillance Network (ILINet), 2) virologic data
      from World Health Organization (WHO) Collaborating and National Respiratory and
      Enteric Virus Surveillance System (NREVSS) Laboratories, 3) Emergency Department
      (ED) syndromic surveillance from Boston, Massachusetts, 4) patient visits for ILI
      from EHR, and 5) reports of ILI from the crowd-sourced system, Flu Near You
      (FNY), by calculating correlations between these systems across four influenza
      seasons, 2012-16, at four different spatial resolutions in the US. For the crowd
      sourced system, we also used a bootstrapping statistical approach to estimate the
      minimum number of reports necessary to produce a meaningful signal at a given
      spatial resolution. RESULTS: In general, as the spatial resolution increased,
      correlation values between all influenza surveillance systems decreased.
      Influenza-like Illness rates in geographic areas with more than 250 crowd-sourced
      participants or with more than 20,000 visit counts for EHR tracked government
      lead estimates of influenza activity. CONCLUSIONS: With a sufficient number of
      reports, data from novel influenza surveillance systems can complement
      traditional healthcare-based systems at multiple spatial resolutions.

PMID- 30111306
TI  - Safety and efficacy of transpupillary silicone oil removal in combination with
      micro-incision phacoemulsification cataract surgery: comparison with 23-gauge
      approach.
AB  - BACKGROUND: To evaluate safety and efficacy of transpupillary silicone oil
      removal combined with micro-incision phacoemulsification cataract surgery, and to
      compare results of transpupillary with 23-gauge three-port vitrectomy approach.
      METHODS: Consecutive cases that underwent silicone oil removal using either
      transpupillary or three-port approach in combination with micro-incision
      phacoemulsification cataract surgery were retrospectively reviewed. The main
      outcome measures were postoperative detachment rate, silicone oil residuals, best
      corrected visual acuity (BCVA) and intraocular pressure (IOP). RESULTS: A total
      of 64 cases were included, 19 in transpupillary and 45 in three-port.
      Postoperative detachment rate within 3 months in transpupillary versus three-port
      was 15.8% versus 4.4% (p = 0.14), Silicone oil residuals was 7.4 +/- 3.2% versus
      7.1 +/- 2.8% (transpupillary vs. three-port, p = 0.71). Preoperative versus
      postoperative BCVA (logMAR) was 1.49 +/- 0.61 versus 1.42 +/- 0.61 in
      transpupillary approach (p = 0.28) and 1.53 +/- 0.48 versus 1.45 +/- 0.57 in
      three-port approach (p = 0.11). Transpupillary approach resulted in lower IOP at
      postoperative day 2 (12.2 +/- 2.3 mmHg vs. 13.5 +/- 2.2 mmHg, p < 0.05), while
      postoperative follow-up at 1 month revealed no significant difference (p = 0.21).
      CONCLUSIONS: Transpupillary silicone oil removal combined with micro-incision
      phacoemulsification cataract surgery is less invasive and can be an alternative
      in some circumstances.

PMID- 30111307
TI  - "Everything else comes first": a mixed-methods analysis of barriers to health
      behaviors among military spouses.
AB  - BACKGROUND: Military spouses are integral to the health of their families, but
      have demonstrated elevated levels of stress, depression, and anxiety.
      Participating in health behaviors such as physical activity and healthy eating
      may have a positive impact on spouses' physical and mental health, but emerging
      evidence suggests spouses' participation in these behaviors is scarce. Thus, the
      purpose of this study was to examine the most frequently reported barriers to
      health behaviors among military spouses. METHODS: Military spouses were recruited
      to complete surveys (N = 230) or participate in focus group sessions (N = 22). On
      the surveys, participants indicated up to 3 of their most frequent barriers to
      physical activity, diet, social connection, and stress management. Responses were
      coded and summed to identify the most commonly reported barriers to each health
      behavior. Subsequently, focus group sessions were conducted to gain a more in
      depth understanding of the challenges military spouses face when trying to
      maintain a healthy lifestyle. Focus group transcripts were coded using thematic
      data analysis to identify the most frequently discussed barriers for each
      behavior. RESULTS: On the surveys, lack of time was the most prevalent barrier
      for physical activity, social connection, and stress management, and the second
      most prevalent barrier for diet. Financial concerns were the most prevalent
      barrier to maintaining a healthy diet. Barriers related to parent/family
      responsibilities were commonly reported across all health behaviors. During the
      focus group sessions, the transient military lifestyle was reported to have a
      significant impact on all of the health behaviors. Other military-related
      stressors including deployments and the necessity to "do it all" alone were
      frequently discussed. Many participants exhibited rigid definitions of what
      "counts" as exercise or health eating. Overall, participants reported sacrificing
      participation in health behaviors to attend to other priorities. CONCLUSIONS:
      Military spouses reported numerous barriers to health behaviors that made it
      difficult for them to prioritize their own health and well-being. Although some
      of the barriers reported were similar to barriers reported by civilians, unique
      stressors associated with military life further impeded participation in health
      behaviors. These findings can be used to inform future health promotion
      interventions for military spouses.

PMID- 30111304
TI  - Colorectal liver metastases: surgery versus thermal ablation (COLLISION) - a
      phase III single-blind prospective randomized controlled trial.
AB  - BACKGROUND: Radiofrequency ablation (RFA) and microwave ablation (MWA) are widely
      accepted techniques to eliminate small unresectable colorectal liver metastases
      (CRLM). Although previous studies labelled thermal ablation inferior to surgical
      resection, the apparent selection bias when comparing patients with unresectable
      disease to surgical candidates, the superior safety profile, and the competitive
      overall survival results for the more recent reports mandate the setup of a
      randomized controlled trial. The objective of the COLLISION trial is to prove non
      inferiority of thermal ablation compared to hepatic resection in patients with at
      least one resectable and ablatable CRLM and no extrahepatic disease. METHODS: In
      this two-arm, single-blind multi-center phase-III clinical trial, six hundred and
      eighteen patients with at least one CRLM (<=3 cm) will be included to undergo
      either surgical resection or thermal ablation of appointed target lesion(s) (<=3
      cm). Primary endpoint is OS (overall survival, intention-to-treat analysis). Main
      secondary endpoints are overall disease-free survival (DFS), time to progression
      (TTP), time to local progression (TTLP), primary and assisted technique efficacy
      (PTE, ATE), procedural morbidity and mortality, length of hospital stay,
      assessment of pain and quality of life (QoL), cost-effectiveness ratio (ICER) and
      quality-adjusted life years (QALY). DISCUSSION: If thermal ablation proves to be
      non-inferior in treating lesions <=3 cm, a switch in treatment-method may lead to
      a reduction of the post-procedural morbidity and mortality, length of hospital
      stay and incremental costs without compromising oncological outcome for patients
      with CRLM. TRIAL REGISTRATION: NCT03088150 , January 11th 2017.

PMID- 30111308
TI  - Moving low value care lists into action: prioritizing candidate health
      technologies for reassessment using administrative data.
AB  - BACKGROUND: Active management of existing health technologies (e.g., devices,
      diagnostic, and/or medical procedures) to ensure the delivery of high value care
      is increasingly recognized around the world. A number of initiatives have raised
      awareness of technologies that may be overused, mis-used, or potentially harmful
      by compiling them into lists of low value care. However, despite the growing
      number of lists, changes to local healthcare practices remain challenging for
      many systems. The objective of this study was to develop and implement a process,
      leveraging existing initiatives and data assets, to produce a list of prioritized
      low value technologies for health technology reassessment (HTR). METHODS: An
      expert advisory committee comprised of clinical experts and health system
      decision-makers was convened to determine key process requirements. Once
      developed, the process was piloted to assess feasibility in the Canadian province
      of British Columbia (BC). RESULTS: The expert advisory committee identified five
      required attributes for the process: data-driven, routine and replicable,
      actionable, stakeholder collaboration, and high return on investment. Guided by
      these attributes, a 5-step process was developed. First, over 1300 published low
      value technologies (i.e., from the National Institute for Health and Care
      Excellence [NICE] "do not do" recommendations, low value technologies in the
      Australian Medical Benefits Schedule, and Choosing Wisely "Top 5" lists) were
      identified. Using appropriate coding systems for BC's administrative health data
      (e.g., International Classification of Diseases [ICD]), the low value
      technologies were queried to examine frequencies and costs of technology use.
      This information was used to rank potential candidates for reassessment based on
      high annual budgetary impact. Lastly, clinical experts reviewed the ranked
      technologies prior to broad dissemination and stakeholder action. Pilot testing
      of the process in BC resulted in the prioritization of 9 initial candidate
      technologies for reassessment. CONCLUSIONS: This is the first account of a
      systematic approach to move a collective body of low value technology
      recommendations into action in a healthcare setting. This work demonstrates the
      feasibility and strength of using administrative data to identify and prioritize
      low value technologies for HTR at a population-level.

PMID- 30111309
TI  - Examining the relationship between sports participation and youth developmental
      outcomes for socially vulnerable youth.
AB  - BACKGROUND: Research has shown that sports participation is positively related to
      youth developmental outcomes, but it is still unknown if sports participation
      relates to these outcomes among socially vulnerable youth. Hence, this research
      aimed to examine the relationship between sports participation and youth
      developmental outcomes (i.e., problem behaviour, pro-social behaviour, school
      performance, subjective health, well-being, self-regulation skills, and sense of
      coherence) for socially vulnerable youth. In addition, the stability of the
      relationship between sports participation and the youth developmental outcomes
      were investigated with a six-month interval. METHODS: Two identical
      questionnaires were administered with a six-month interval by youth professionals
      from four youth organisations, measuring the youth developmental outcomes and
      sports participation rates of socially vulnerable youth. In total, 283 socially
      vulnerable youths (average 14.68 years old) participated at baseline and 187
      youths after six months. RESULTS: The results showed that sports participation
      was positively related to pro-social behaviour, subjective health, well-being,
      and sense of coherence at both measurements. We found no evidence for the
      relationship between sports participation and problem behaviour and the self
      regulatory skills. In addition, sports participation was only positively related
      to school performance at the first, but not at the second, measurement.
      CONCLUSIONS: The results of this study show that there are positive relationships
      between sports participation and several youth developmental outcomes. Based on
      the current data no conclusions can be drawn about the causal relationship
      between sports participation and youth developmental outcomes. Given the focus of
      policymakers and health professionals on sport as a means to achieve wider social
      and educational outcomes for young people, including in the Netherlands, further
      research is needed to shed light on the relationship between sports participation
      and youth developmental outcomes for socially vulnerable youth, with a special
      focus on this group's heterogeneity. TRIAL REGISTRATION: Trialregister.nl NTR4621
      Date of Registration: 2 June 2014 (retrospectively registered).

PMID- 30111310
TI  - Lower extremity joint contracture according to ambulatory status in children with
      Duchenne muscular dystrophy.
AB  - BACKGROUND: Lower extremity joint contractures have negative effects on gait in
      children with Duchenne muscular dystrophy (DMD). Thus, contracture prevention is
      essential for maintaining a patient's functional ability and an acceptable
      quality of life. This study investigated hip flexion (HF), knee flexion (KF), and
      ankle joint plantar flexion (APF) contractures among male patients with DMD,
      based on the patients' ambulatory status. Differences in major joint
      contractures, based on passive stretching exercise participation, were also
      investigated. METHODS: A total of 128 boys with DMD, followed at the DMD clinic
      of a tertiary care hospital, were included in this cross-sectional study. The
      passive ranges-of-motion of the hip, knee, and ankle joints were measured, in the
      sagittal plane, using a goniometer. The Vignos Scale was used to grade ambulatory
      function. Boys with DMD who performed stretching exercises for more than 5
      min/session, > 3 sessions/week, were classified into the stretching group.
      RESULTS: The HF (23.5o), KF (43.5o), and APF (34.5o) contracture angles in the
      non-ambulatory group were more severe than those in the ambulatory group. APF
      contractures (41 patients, 52.6%) were more frequently observed early, even
      within the ambulatory period, than were hip (8 patients, 10.3%), and knee joint
      (17 patients, 21.8%) contractures. Passive stretching exercises > 3 sessions/week
      were not associated with the degree of lower extremity joint contractures in the
      ambulatory or non-ambulatory group. CONCLUSION: HF, KF, and APF contractures are
      more common and severe when there is deterioration of ambulatory function.
      Stretching exercises alone are unlikely to prevent lower extremity joint
      contractures.

PMID- 30111311
TI  - Open reduction and internal fixation with bone grafts for comminuted mason type
      II radial head fractures.
AB  - BACKGROUND: The use of bone graft for the radial head fractures has been
      previously described and occasionally used by other authors.This is the first
      paper, to my knowledge, dealing with the relevant issue about the importance that
      the use of an autologous bone graft can have on the radial head fractures.
      METHODS: From July 2010 to July 2014, 20 consecutive patients who underwent open
      reduction and internal fixation for a closed Mason type II radial head fracture
      were retrospectively reviewed. Patients with Mason type I, III, simple type II,
      and comminuted type II fractures treated without bone grafting were excluded. A
      clinical examination and radiographic evaluation were performed. The overall
      functional result was evaluated using the Mayo Elbow Performance Score (MEPS).
      The Broberg and Morrey classification was used to evaluate traumatic arthritis.
      RESULTS: The average follow-up duration was 31 months (range, 24-50 months). Bone
      union of the radial head fracture was achieved in all patients at an average of
      13.5 weeks (range, 12-17 weeks). Postoperative radiographs showed no cases of
      postsurgical ligamentous instability, necrosis of the radial head, or internal
      fixation failure. The mean range of motion of the affected elbow was 128 degrees 
      +/- 8.4 degrees  in flexion, 14.5 degrees  +/- 11.1 degrees  in extension, 68.7
      degrees  +/- 14.1 degrees  in pronation, and 65.2 degrees  +/- 18.2 degrees  in
      supination. The mean MEPS was 92 +/- 7.9 points (range, 80-100); the outcome was
      excellent (90-100 points) in 13 patients and good (75-89 points) in 7 patients.
      The MEPS tended to be higher in patients with an isolated fracture (p = 0.016).
      Based on the Broberg and Morrey classification for radiographic assessment of
      post-traumatic arthritis, 15 elbows had no evidence of degenerative changes
      (grade 0), and 5 elbows had grade 1 changes. CONCLUSION: Although radial head
      fractures may not be amenable to internal fixation, our findings suggest that
      open reduction and internal fixation with an autogenous bone graft from the
      lateral epicondyle of the humerus provides satisfactory elbow function in
      patients with comminuted Mason type II radial head fractures.

PMID- 30111312
TI  - The effects of empathy skills training on nursing students' empathy and attitudes
      toward elderly people.
AB  - BACKGROUND: Nursing students' empathy and positive attitudes toward elderly
      people could help provide improved elderly care in their future practice. This
      study aimed to investigate the effects of empathy skills training on nursing
      students' empathy and attitudes toward elderly people. METHODS: This quasi
      experimental study was conducted in Yasuj, Iran in 2014. The sample consisted of
      63 students at Hazrat Zeinab Nursing and Midwifery School who were randomly
      divided into a control (n = 31) and an intervention group (n = 32). The
      intervention group attended an eight-hour workshop on empathy skills that was
      presented through lectures, demonstration, group discussions, scenarios, and
      questioning. The data were collected using the Persian versions of Kogan's
      Attitudes towards Old People Scale and Jefferson Scale of Physician Empathy
      Health Professionals Version. Then, the data were entered into the SPSS software,
      version 19 and were analyzed using descriptive statistics, chi-square test, t
      test, and repeated measures analysis of variance. RESULTS: The results showed
      that the empathy skills training program had a significant impact on the
      students' mean scores of empathy and attitudes toward elderly people (p < 0.001).
      The intervention group's mean score of empathy increased from 77.8 (SD = 10.7)
      before the intervention to 86 (SD = 7.3) immediately after that and 85.2 (SD =
      8.9) 2 months later. Their mean score of attitude also increased from 110.8 (SD =
      10.9) before the intervention to 155.2 (SD = 23.4) immediately after the
      intervention and 158.6 (SD = 23.2) 2 months later. Additionally, the empathy and
      attitude scores of the intervention group were significantly higher than those
      for control group immediately and 2 months after the intervention. CONCLUSIONS:
      Empathy skills training improved the nursing students' empathy and attitudes
      towards elderly people. Therefore, empathy training is recommended to be
      incorporated into the undergraduate nursing curriculum.

PMID- 30111314
TI  - Malaria control and chemoprophylaxis policy in the Republic of Korea Armed Forces
      for the previous 20 years (1997-2016).
AB  - BACKGROUND: Vivax malaria reemerged along the Demilitarized Zone (DMZ), Republic
      of Korea (ROK), in 1993. While it was hypothesized that vivax malaria would
      spread throughout the peninsula, nearly all cases were due to exposure near the
      DMZ. To reduce spillover of vivax malaria to the civilian community, the ROK
      Ministry of National Defense (MND) initiated malaria prevention policies
      including a large-scale chemoprophylaxis programme in malaria high-risk areas in
      1997. The present study investigated the overall changes in the incidence of
      malaria among ROK soldiers and the mass chemoprophylaxis program from 1997 to
      2016. RESULTS: Peak numbers of vivax malaria were reported in 2000, with most
      cases reported near the DMZ, before declining to the current levels. To combat
      the rapid increase in the number of malaria cases and its expansion throughout
      the ROK, the MND implemented mosquito control and personal protection programmes.
      The MND also implemented a large-scale vivax malaria chemoprophylaxis programme
      using hydroxychloroquine (400 mg weekly) in 1997, and primaquine (15 mg * 14
      days) as terminal chemoprophylaxis in 2001. Additionally, an improved medical
      system enabled the rapid detection and treatment of malaria to reduce morbidity
      and decrease transmission of malaria from humans to mosquitoes. Following the
      full implementation of these programmes, the incidence of vivax malaria declined
      in both ROK Armed Forces and civilian populations. Subsequently, several changes
      in the ROK Armed Forces chemoprophylaxis programme were implemented, including
      the reduction of the period of hydroxychloroquine prophylaxis by 2 months (2008)
      and other changes in the chemoprophylaxis policy, e.g., only ROK Armed Forces
      personnel in moderate risk groups received terminal primaquine chemoprophylaxis
      (2011), and in 2016, the discontinuation of terminal primaquine chemoprophylaxis
      in moderate-risk area. CONCLUSIONS: The resurgence of vivax malaria in the ROK
      Armed Forces personnel near the DMZ was successfully suppressed through the
      implementation of a mass malaria chemoprophylaxis programme initiated by the MND
      in 1997, as well as several other factors that may have contributed to the
      reduction of malaria transmission since 2000. Given the current malaria situation
      in the ROK and North Korea, it is necessary to reevaluate the ROK Armed Forces
      and civilian malaria control policies.

PMID- 30111313
TI  - Emerging function and potential diagnostic value of circular RNAs in cancer.
AB  - As a novel class of endogenous RNAs, circRNAs, have a covalently closed
      continuous loop, with neither a 5'to 3'polarity, nor a polyadenylated tail.
      Numerous circRNAs have been characterized by abundance, stabilization,
      conservation, and exhibit tissue/developmental stage-specific expression.
      Furthermore, circRNAs play vital roles in tumorigenesis and metastasis, such as
      functioning as a ceRNA or miRNA sponge, interacting with protein and encoding
      protein. Increasing evidence has revealed that it potentially serves as a
      required novel biomarker for cancer diagnosis. This review summarized the latest
      research on circRNAs, including its classification and biogenesis, mechanism and
      functions, as well as circRNAs in different cancers, as a potential biomarker.

PMID- 30111315
TI  - Blood pressure components and incident cardiovascular disease and mortality
      events among Iranian adults with chronic kidney disease during over a decade long
      follow-up: a prospective cohort study.
AB  - BACKGROUND: To explore the association between systolic and diastolic blood
      pressure (SBP and DBP respectively) and pulse pressure (PP) with cardiovascular
      disease (CVD) and mortality events among Iranian patients with prevalent CKD.
      METHODS: Patients [n = 1448, mean age: 60.9 (9.9) years] defined as those with
      estimated glomerular filtration rate < 60 ml/min/1.73 m2, were followed from 31
      January 1999 to 20 March 2014. Multivariable Cox proportional hazard models were
      applied to examine the associations between different components of BP with
      outcomes. RESULTS: During a median follow-up of 13.9 years, 305 all-cause
      mortality and 317 (100 fatal) CVD events (among those free from CVD, n = 1232)
      occurred. For CVD and CV-mortality, SBP and PP showed a linear relationship,
      while a U-shaped relationship for DBP was observed with all outcomes. Considering
      120 <= SBP < 130 as reference, SBP >= 140 mmHg was associated with the highest
      hazard ratio (HR) for CVD [1.68 (1.2-2.34)], all-cause [1.72 (1.19-2.48)], and CV
      mortality events [2.21 (1.16-4.22)]. Regarding DBP, compared with 80 <= DBP < 85
      as reference, the level of >= 85 mmHg increased risk of CVD and all-cause
      mortality events; furthermore, DBP < 80 mmHg was associated with significant HR
      for CVD events [1.55 (1.08-2.24)], all-cause [1.68 (1.13-2.5)] and CV-mortality
      events [3.0 (1.17-7.7)]. Considering PP, the highest HR was seen in participants
      in the 4th quartile for all outcomes of interest; HRs for CVD events [1.92 (1.33
      2.78)], all-cause [1.71 (1.11-2.63)] and CV-mortality events [2.22 (1.06-4.64)].
      CONCLUSIONS: Among patients with CKD, the lowest risk of all-cause and CV
      mortality as well as incident CVD was observed in those with SBP < 140, 80 <= DBP
      < 85 and PP < 64 mmHg.

PMID- 30111316
TI  - What were they thinking when providing preference measurements for generic health
      states? The evidence for HUI3.
AB  - BACKGROUND: Multi-attribute generic preference-based measures of health-related
      quality of life are used as comprehensive outcome measures. Typically preferences
      for health states defined by these systems are elicited from a representative
      sample of the general population. An important element in that elicitation
      process is the information that respondents were instructed to consider in
      providing their responses. METHODS: A random sample of community-dwelling
      respondents in Canada was surveyed in face-to-face interviews. Respondents
      provided preference scores for selected Health Utilities Index Mark 3 (HUI3)
      health states. Respondents also answered questions about the most important
      attributes and the importance of various impacts of the health states in
      providing their preference scores. RESULTS: Fifty per cent of respondents
      reported that they focussed on two, and 21% on three, attributes of the eight
      HUI3 attributes. Each of the eight attributes was identified as important; pain
      (49%), vision (37%), cognition (34%), emotion (28%), and ambulation (28%) were
      the most important. The null hypothesis that all of the attributes were equally
      important was rejected (p < 0.001). With respect to the impacts, 89% of
      respondents indicated that the ability to take care of oneself was quite or very
      important; similarly 76% reported the same for impact on family life, 69% for
      impact on the happiness of others, 61% for the impact on their ability to work,
      and 42% for the impact on their leisure activities. The null hypothesis that all
      of the impacts were equally important was rejected (p < 0.001). CONCLUSIONS: In
      providing preference scores for HUI3 health states, respondents thoughtfully
      examined the implications of the health states for their ability to live, work,
      socialize, and function.

PMID- 30111317
TI  - The role of splenectomy in lipid metabolism and atherosclerosis (AS).
AB  - The extensive performance of splenectomy worldwide for patients suffered from
      splenic trauma has given rise to high risks of postoperative complications, which
      has been attracting increasing attention in recent years. Nowadays the spleen is
      regarded as a versatile organ of the human body, invested with various excellent
      properties. The spleen has been recognized to take a great part in lipid
      metabolism. While removal of the spleen intends to alter lipid values, especially
      with an elevated LDL, splenic autotransplantation is able to normalize these
      lipid alterations. What is more, conservative surgical procedures like subtotal
      or partial splenectomy, could as well, afford a correction of dyslipidemia. At
      the same time, clinically, splenectomy demonstrates a high rate of
      atherosclerosis (AS), whereas non-surgical treatment after splenic trauma shows
      unchanged propagation of AS. Based on the intimate relationship between serum
      lipids and AS, the lipid changes modulated by splenectomy are believed to be
      responsible for the development of AS. Therefore, a "splenic factor" is most
      likely present in the regulation of lipidation and AS. Several theories have been
      postulated to elucidate the possible mechanism involved, among which most are
      primarily based on its forceful natural immune function, that is to say, the
      mononuclear phagocytic system.However, the accurate mechanisms behind this
      mysterious phenomenon still remain unclear so far. Of importance, lipid fractions
      should be monitored consecutively in case of inevitable splenectomy.

PMID- 30111318
TI  - Peroxiredoxin I maintains luteal function by regulating unfolded protein
      response.
AB  - BACKGROUND: Mounting evidence shows that ROS regulation by various antioxidants
      is essential for the expression of enzymes involved in steroidogenesis and
      maintenance of progesterone production by the corpus luteum (CL). However, the
      underlying mechanisms of peroxiredoxin 1 (PRDX1), an antioxidant enzyme, in
      luteal function for progesterone production in mice have not been reported. The
      aim of this study was to evaluate the functional link between PRDX1 and
      progesterone production in the CL of Prdx1 knockout (K/O) mice in the functional
      stage of CL. METHODS: The expression pattern of the unfolded protein response
      (UPR) signaling pathways, endoplasmic reticulum (ER) stress-induced apoptosis
      related genes and peroxiredoxins 1 (PRDX1) were investigated by western blotting
      analysis in CL tissue of 10 weeks mice during functional stage of CL. The protein
      levels of these genes after ER-stress inducer tunicamycin (Tm), ER-stress
      inhibitor tauroursodeoxycholic acid (TUDCA) and ROS scavenger, N-acetylcysteine
      (NAC) stimulation by intraperitoneal (i.p) injection were also investigated in CL
      tissue of wild type (WT) mice. Finally, we examined progesterone production and
      UPR signaling related gene expression in CL tissue of Prdx1 K/O mice. RESULTS: We
      demonstrated that PRDX1 deficiency in the functional stage activates the UPR
      signaling pathways in response to ER stress-induced apoptosis. Interestingly, CL
      number, serum progesterone levels, and steroidogenic enzyme expression in Prdx1
      K/O mice decreased significantly, compared to those in wild type mice. Levels of
      UPR signaling pathway markers (GRP78/BIP, P50ATF6, and phosphorylated (p)-eIF2)
      and ER-stress associated apoptotic factors (CHOP, p-JNK, and cleaved caspase-3)
      were dramatically increased in the CL tissue of Prdx1 K/O mice. In addition,
      administration of the NAC, reduced progesterone production and activated ER
      stress-induced UPR signaling in the CL tissue obtained from the ovary of Prdx1
      K/O mice. Taken together, these results indicated that reduction in serum
      progesterone levels and activation of ER-stress-induced UPR signaling are
      restored by NAC injection in the CL of Prdx1 K/O mice. CONCLUSION: These
      observations provide the first evidence regarding the basic mechanisms connecting
      PRDX1 and progesterone production in the functional stage of CL.

PMID- 30111319
TI  - Socioeconomic inequalities in newborn care during facility and home deliveries: a
      cross sectional analysis of data from demographic surveillance sites in rural
      Bangladesh, India and Nepal.
AB  - BACKGROUND: In Bangladesh, India and Nepal, neonatal outcomes of poor infants are
      considerably worse than those of better-off infants. Understanding how these
      inequalities vary by country and place of delivery (home or facility) will allow
      targeting of interventions to those who need them most. We describe socio
      economic inequalities in newborn care in rural areas of Bangladesh, Nepal and
      India for all deliveries and by place of delivery. METHODS: We used data from
      surveillance sites in Bangladesh, India and from Makwanpur and Dhanusha districts
      in Nepal, covering periods from 2001 to 2011. We used literacy (ability to read a
      short text) as indicator of socioeconomic status. We developed a composite score
      of nine newborn care practices (score range 0-9 indicating infants received no
      newborn care to all nine newborn care practices). We modeled the effect of
      literacy and place of delivery on the newborn care score and on individual
      practices. RESULTS: In all study sites (60,078 deliveries in total), use of
      facility delivery was higher among literate mothers. In all sites, inequalities
      in newborn care were observed: the difference in new born care between literate
      and illiterate ranged 0.35-0.80. The effect of literacy on the newborn care score
      reduced after adjusting for place of delivery (range score difference literate
      illiterate: 0.21-0.43). CONCLUSION: Socioeconomic inequalities in facility care
      greatly contribute to inequalities in newborn care. Improving newborn care during
      home deliveries and improving access to facility care are a priority for
      addressing inequalities in newborn care and newborn mortality.

PMID- 30111320
TI  - Surgical treatment of children with total colonic aganglionosis: functional and
      metabolic long-term outcome.
AB  - BACKGROUND: Total colonic aganglionosis (TCA) is a rare variant of Hirschsprung's
      disease occurring in 3-10% of the cases. Only few studies reported the long-term
      clinical and metabolic outcomes of patients with TCA. The aim of this study was
      to evaluate the functional and metabolic long-term outcomes of children
      undergoing surgical treatment for TCA. METHODS: A 15-year retrospective study was
      performed. Blood chemistry tests and stool analysis performed at the last follow
      up visit were recorded. Height and weight development were assessed using the
      corresponding percentiles for age. Faecal continence and quality of life were
      evaluated using a detailed questionnaire. RESULTS: Eleven patients were included
      in the study. The median age at surgery was 6 months (range: 3-72 months). After
      histological confirmation, all patients underwent a total colectomy. Ileoanal
      anastomosis (n = 6), ileorectal anastomosis (n = 1), J-pouch (n = 1) and Duhamel
      procedure (n = 3) were performed. Temporary ileostomy was closed after a median
      of 8 weeks in 10/11 patients. After a median follow-up of 78 months (range: 27
      199 months), all evaluated patients were continent. Height and weight were
      appropriate for age in only 5 patients. Vitamin B12 and folic acid serum levels
      were normal in all examined patients. Ten patients had normal hemoglobin serum
      levels. Seven patients had low transferrin saturation in serum. Hemoccult tests
      were negative in all examined patients. Despite complex postoperative courses in
      some cases, patients and parents showed good overall satisfaction in terms of
      quality of life. CONCLUSION: The majority of patients reported a good quality of
      life. This can result from the adaptation of the patients to certain disease
      states. The failure to thrive seems to be related with the extent of
      aganglionosis. The inclusion of these patients in interdisciplinary long-term
      follow-up care, in which pediatric surgeons, gastroenterologists, and dieticians
      are involved, is essential.

PMID- 30111321
TI  - Effectiveness of clarithromycin in patients with yellow nail syndrome.
AB  - BACKGROUND: Yellow nail syndrome (YNS) is a rare disease characterized by the
      triad of thickened, slow-growing yellow nails, lymphedema, and chronic
      respiratory manifestations. The cause of YNS is not known; however, it is
      suggested to be due to a congenital lymph abnormality. Since YNS is accompanied
      by chronic bronchial infection in more than half of patients, we hypothesized
      that treatment with clarithromycin (CAM) could be effective. We therefore
      evaluated the effectiveness of CAM against nail discoloration and respiratory
      manifestation in patients with YNS. METHODS: We conducted an observational study
      involving 5 patients with YNS who were treated at our institution between January
      2005 and January 2016. CAM was prescribed for every patient. Patient demographic
      information, comorbidities, medications, chest radiographs, and clinical data
      such as nail color were extracted to evaluate clinical outcome. RESULTS: Mean
      patient age was 71.6 years, and 2 patients (40%) were male. Four patients had
      sinusitis, and 2 had rheumatoid arthritis. Regarding respiratory manifestations,
      4 patients had sinobronchial syndrome and 2 had pleural effusion. Nail
      discoloration improved in every patient after CAM treatment. Four patients also
      experienced improvement in their respiratory manifestations. CONCLUSIONS: In
      patients with YNS, the anti-inflammatory activity of macrolides might improve
      their systemic inflammation. This improvement could help to reduce lymphedema and
      promote nail growth. TRIAL REGISTRATION: Ethical approval was provided by the
      institutional review board of the National Center of Global Health and Medicine
      (NCGM-G-002143-00), in January 2017. This study is retrospectively registered for
      UMIN Clinical Trial Registry ( UMIN000028514 ) in August 4th, 2017.

PMID- 30111322
TI  - Fast and expensive (PCR) or cheap and slow (culture)? A mathematical modelling
      study to explore screening for carbapenem resistance in UK hospitals.
AB  - BACKGROUND: Enterobacteriaceae are a common cause of hospital infections.
      Carbapenems are a clinically effective treatment of such infections. However,
      resistance is on the rise. In particular, carbapenemase-producing carbapenem
      resistant Enterobacteriaceae (CP-CRE) are increasingly common. In order to limit
      spread in clinical settings, screening and isolation is being recommended, but
      many different screening methods are available. We aimed to compare the impact
      and costs of three algorithms for detecting CP-CRE carriage. METHODS: We
      developed an individual-based simulation model to compare three screening
      algorithms using data from a UK National Health Service (NHS) trust. The first
      algorithm, "Direct PCR", was highly sensitive/specific and quick (half a day),
      but expensive. The second, "Culture + PCR", was relatively sensitive/specific but
      slower, requiring 2.5 days. A third algorithm, "PHE", repeated the "Culture +
      PCR" three times with an additional PCR. Scenario analysis was used to compare
      several levels of CP-CRE prevalence and coverage of screening, different
      specialities as well as isolation strategies. Our outcomes were (1) days that a
      patient with CP-CRE was not detected and hence not isolated ("days at risk"), (2)
      isolation bed days, (3) total costs and (4) mean cost per CP-CRE risk day averted
      per year. We also explored limited isolation bed day capacity. RESULTS: We found
      that although a Direct PCR algorithm would reduce the number of CP-CRE days at
      risk, the mean cost per CP-CRE risk day averted per year was substantially higher
      than for a Culture + PCR algorithm. For example, in our model of an intensive
      care unit, during a year with a 1.6% CP-CRE prevalence and 63% screening
      coverage, there were 508 (standard deviation 15), 642 (14) and 655 (14) days at
      risk under screening algorithms Direct PCR, Culture + PCR and PHE respectively,
      with mean costs per risk day averted of L192, L61 and L79. These results were
      robust to sensitivity analyses. CONCLUSIONS: Our results indicate that a Culture
      + PCR algorithm provides the optimal balance of cost and risk days averted, at
      varying isolation, prevalence and screening coverage scenarios. Findings from
      this study will help clinical organisations determine the optimal screening
      approach for CP-CRE, balancing risk and resources.

PMID- 30111324
TI  - What prevents midwifery quality care in Bangladesh? A focus group enquiry with
      midwifery students.
AB  - BACKGROUND: With professional midwives being introduced in Bangladesh in 2013,
      the aim of this study was to describe midwifery students perceptions on midwives'
      realities in Bangladesh, based on their own experiences. METHOD: Data were
      collected through 14 focus group discussions that included a total of 67 third
      year diploma midwifery students at public nursing institutes/colleges in
      different parts of Bangladesh. Data were analyzed deductively using an analytical
      framework identifying social, professional and economical barriers to the
      provision of quality care by midwifery personnel. RESULTS: The social barriers
      preventing midwifery quality care falls outside the parameters of Bangladeshi
      cultural norms that have been shaped by beliefs associated with religion,
      society, and gender norms. This puts midwives in a vulnerable position due to
      cultural prejudice. Professional barriers include heavy workloads with a shortage
      of staff who were not utilized to their full capacity within the health system.
      The reason for this was a lack of recognition in the medical hierarchy, leaving
      midwives with low levels of autonomy. Economical barriers were reflected by lack
      of supplies and hospital beds, midwives earning only low and/or irregular
      salaries, a lack of opportunities for recreation, and personal insecurity related
      to lack of housing and transportation. CONCLUSION: Without adequate support for
      midwives, to strengthen their self-confidence through education and through
      continuous professional and economic development, little can be achieved in terms
      of improving quality care of women during the period around early and late
      pregnancy including childbirth.The findings can be used for discussions aimed to
      mobilize a midwifery workforce across the continuum of care to deliver quality
      reproductive health care services. No matter how much adequate support is
      provided to midwives, to strengthen their self-confidence through education,
      continuous professional and economic development, addressing the social barriers
      is a prerequisite for provision of quality care.

PMID- 30111325
TI  - YKL-40 is highly expressed in the epicardial adipose tissue of patients with
      atrial fibrillation and associated with atrial fibrosis.
AB  - BACKGROUND: YKL-40 (CHI3L1) is a novel biomarker for inflammation, tissue
      remodeling, and fibrosis, as well as cardiovascular diseases. We investigated the
      association between YKL-40 expression in epicardial adipose tissue (EAT) and
      atrial fibrosis in patients with atrial fibrillation (AF). METHODS: Blood
      samples, subcutaneous adipose tissue (SAT), paracardial adipose tissue (PAT),
      EAT, and adjacent atrial myocardium were acquired from patients receiving
      coronary artery bypass grafts. The patients were divided into the AF group (n =
      28) and the sinus rhythm (SR) group (n = 36). RESULTS: We did not detect a
      significant difference in the serum YKL-40 levels in the SR and AF groups (P =
      0.145). Quantitative real-time PCR showed that YKL-40 (CHI3L1) mRNA levels in the
      EAT were significantly higher than in the SAT or PAT of AF patients, or the EAT
      of SR patients (All P < 0.001). We found similar results for YKL-40 protein
      levels by immunohistochemistry. Masson staining showed significantly more
      fibrosis in AF patients than in SR patients (P < 0.001). Western blotting
      indicated that AF patients had significantly higher expression of collagen I (P =
      0.039). We found a linear relationship between YKL-40 mRNA expression and the
      collagen volume fraction of the atrial myocardium (y = 3.576x + 26.205, P <
      0.001). Multivariate linear regression analysis revealed that body mass index is
      an independent risk factor for YKL-40 expression in EAT (beta = 0.328, P =
      0.011). CONCLUSIONS: YKL-40, which is highly expressed in the EAT of patients
      with AF, is affected by body mass index and associated with atrial fibrosis,
      which may contribute to the development of AF.

PMID- 30111323
TI  - Exosomes derived from mesenchymal stem cells enhance radiotherapy-induced cell
      death in tumor and metastatic tumor foci.
AB  - BACKGROUND: We have recently shown that radiotherapy may not only be a successful
      local and regional treatment but, when combined with MSCs, may also be a novel
      systemic cancer therapy. This study aimed to investigate the role of exosomes
      derived from irradiated MSCs in the delay of tumor growth and metastasis after
      treatment with MSC + radiotherapy (RT). METHODS: We have measured tumor growth
      and metastasis formation, of subcutaneous human melanoma A375 xenografts on
      NOD/SCID-gamma mice, and the response of tumors to treatment with radiotherapy (2
      Gy), mesenchymal cells (MSC), mesenchymal cells plus radiotherapy, and without
      any treatment. Using proteomic analysis, we studied the cargo of the exosomes
      released by the MSC treated with 2 Gy, compared with the cargo of exosomes
      released by MSC without treatment. RESULTS: The tumor cell loss rates found after
      treatment with the combination of MSC and RT and for exclusive RT, were: 44.4% %
      and 12,1%, respectively. Concomitant and adjuvant use of RT and MSC, increased
      the mice surviving time 22,5% in this group, with regard to the group of mice
      treated with exclusive RT and in a 45,3% respect control group. Moreover, the
      number of metastatic foci found in the internal organs of the mice treated with
      MSC + RT was 60% less than the mice group treated with RT alone. We reasoned that
      the exosome secreted by the MSC, could be implicated in tumor growth delay and
      metastasis control after treatment. CONCLUSIONS: Our results show that exosomes
      derived form MSCs, combined with radiotherapy, are determinant in the enhancement
      of radiation effects observed in the control of metastatic spread of melanoma
      cells and suggest that exosome-derived factors could be involved in the
      bystander, and abscopal effects found after treatment of the tumors with RT plus
      MSC. Radiotherapy itself may not be systemic, although it might contribute to a
      systemic effect when used in combination with mesenchymal stem cells owing the
      ability of irradiated MSCs-derived exosomes to increase the control of tumor
      growth and metastasis.

PMID- 30111327
TI  - Beyond cure: patient reported outcomes of hepatitis C treatment among people who
      inject drugs in Australia.
AB  - BACKGROUND: Recent advances in the treatment of hepatitis C virus (HCV) infection
      provide the possibility of eliminating HCV as a public health threat. This focus
      on HCV elimination through treatment, however, is also driving a concomitant
      focus on 'achieving cure' as the primary outcome of treatment. The aim of this
      paper is to explore what people who inject drugs consider to be important in
      relation to outcomes of HCV treatment, and whether there are outcomes 'beyond
      cure' that might be important to understand as part of improving engagement in
      treatment. METHODS: A peer researcher with experience of both HCV treatment and
      injecting drug use conducted interviews with 24 people in the following groups in
      Melbourne, Australia: (1) people who had refused or deferred HCV treatment; (2)
      people who were actively thinking about, planning and/or about to commence HCV
      treatment; (3) people currently undertaking HCV treatment and (4) people who had
      recently completed HCV treatment. RESULTS: The findings show that people who
      inject drugs are seeking outcomes 'beyond cure' including improved physical and
      mental health, positive changes in identity and social relationships and managing
      future health and risk. Participants indicated that these other outcomes had not
      been addressed within their experience of HCV treatment. CONCLUSION: While cure
      is an obvious outcome of HCV treatment, patients are seeking change in other
      areas of their lives. This study also provides valuable insights for the
      development of patient-reported measures in this context, which would be an
      important step towards more patient-centred approaches to HCV treatment.

PMID- 30111326
TI  - Age and African-American race impact the validity and reliability of the asthma
      control test in persistent asthmatics.
AB  - BACKGROUND: The Asthma Control Test (ACT) is widely used to assess asthma
      control, yet the validity and reliability of the test have not been specifically
      evaluated in adolescents or African-Americans. We conducted a prospective
      psychometric study of the ACT in African-American (AA) and non-African-American
      (nAA) adolescents with persistent asthma, with emphasis on the clinical utility
      of the test for medical decision making. METHODS: Participants completed the ACT
      and performed spirometry. A physician conducted a guidelines-based assessment of
      asthma control, blinded to the ACT score. Study procedures were repeated 6-8
      weeks later. The ACT-based asthma control assessment was compared to physician
      assessment. RESULTS: For baseline and follow-up visits, internal consistency, as
      measured using Cronbach's alpha, was 0.80 and 0.81 in AA teens and 0.80 and 0.83
      in nAA teens. Intraclass correlation coefficients were 0.59 and 0.76 in AA and
      nAA teens, respectively, with stable asthma control over time. Agreement between
      ACT and physician assessment was moderate in AA teens and fair in nAA teens. An
      ACT score of <=19 showed reduced sensitivity for not well controlled asthma in
      both groups, while a score of <=21 had the greatest area under the ROC curve. ACT
      scores were marginally responsive to change in control status. CONCLUSIONS:
      Concerns for the ACT's ability to detect uncontrolled asthma in adolescents
      emphasizes the need for a more comprehensive evaluation of asthma control in
      clinical settings. A higher threshold ACT score to define not well controlled
      asthma may be needed if the ACT is to be used for medical decision making. TRIAL
      REGISTRATION: ClinicalTrials.gov: NCT02671643 , NCT02662413 .

PMID- 30111329
TI  - The health needs and access barriers among refugees and asylum-seekers in
      Malaysia: a qualitative study.
AB  - BACKGROUND: In Malaysia, refugees and asylum-seekers are a vulnerable group that
      often face circumstances in which their health and wellbeing can be compromised.
      This qualitative study sought to examine the key health concerns and barriers to
      healthcare access among refugees and asylum-seekers in Malaysia through the lens
      of healthcare professionals, program staff and experts on refugee and migrant
      health. METHODS: We conducted 20 semi-structured in-depth interviews with
      experts, healthcare professionals, program managers or executives from UN
      agencies, public healthcare facilities, civil society organizations, and academic
      institutions in Malaysia. Interviews were transcribed and analyzed both
      deductively and inductively using thematic analysis. RESULTS: Participant
      narratives highlight that the health needs of refugees and asylum-seekers in
      Malaysia are complex. As reported, access to healthcare is underpinned by
      numerous social, cultural and economic determinants compounded by a legal
      environment that lacks inclusivity of refugees and asylum-seekers. Apart from the
      health risks associated with the migration process, limited access to
      comprehensive healthcare post-arrival remain a problem for refugees and asylum
      seekers in Malaysia. Key barriers to healthcare access are linked to poor health
      literacy and the lack of awareness on one's right to healthcare; language and
      cultural differences; protection issues resulting from a lack of legal status;
      and an inability to afford healthcare due to inadequate livelihoods. Overall,
      poor access to healthcare is perceived to have detrimental consequences on the
      health status of refugees, asylum-seekers and its host population, and may incur
      greater costs to the health system in the long run. CONCLUSION: Comprehensive
      efforts in practice and research that tackle the social, cultural and economic
      determinants of health, and more inclusive health policies are crucial in
      strengthening healthcare access among refugees and asylum-seekers in Malaysia.
      Practical recommendations include improving the health literacy of refugees and
      asylum-seekers for better navigation of the health system; bridging language and
      cultural gaps through translation support and inter-cultural orientation;
      implementing policies grounded in the right to healthcare for all regardless of
      legal status and in the interest of public health; and establishing a larger
      evidence base to drive policy development and implementation for refugee health
      within the Malaysian context.

PMID- 30111328
TI  - Isolation, characterization, and biological evaluation of a potent anti-malarial
      drimane sesquiterpene from Warburgia salutaris stem bark.
AB  - BACKGROUND: Malaria continues to be a global burden as the efficacy of most
      commercial anti-malarial drugs has been compromised by the evolution of parasite
      resistance. With the urgent need created for the development of alternative and
      more efficient anti-malarial drugs, this study focused on the evaluation of anti
      malarial agents of the Warburgia salutaris stem bark. METHODS: The stem bark was
      extracted with dichloromethane followed by silica gel column chromatography that
      led to the isolation of iso-mukaadial acetate, a drimanoid sesquiterpene. This
      compound was characterized by spectroscopic analysis (1H NMR, 13C NMR, IR and
      MS), and its structure was confirmed by X-ray crystallography. In vitro anti
      plasmodial activity was investigated using a chloroquine sensitive NF54
      Plasmodium falciparum strain. Cytotoxicity was measured using the MTT assay on
      HEK239 and HEPG2 cell lines. Chloroquine-sensitive Plasmodium berghei was used to
      infect Sprague-Dawley rats for in vivo studies. The W. salutaris crude extract
      and iso-mukaadial acetate were administered orally at 0.5; 1.5, 2.5 and 5 mg/kg,
      chloroquine was used as the reference drug. Determination of percentage
      parasitaemia, haematological parameters, and rat body weights was done throughout
      the experimental study period. RESULTS: The crude extract and iso-mukaadial
      acetate showed very good activity on the inhibition of parasite growth (IC50 0.01
      +/- 0.30 ug/ml) and (IC50 0.44 +/- 0.10 ug/ml), respectively, with iso-mukaadial
      acetate having cytotoxicity activity of 36.7 +/- 0.8 and 119.2 +/- 8.8 (ug/ml) on
      HEK293 and HEPG2 cells, respectively. The crude extract and iso-mukaadial acetate
      reduced percentage parasitaemia in a dose-dependent manner in comparison to the
      control. There were no significant differences in the haematological parameters
      in all the experimental groups in comparison to control group. This study proves
      that W. salutaris contains components (including iso-mukaadial acetate) that
      exhibit anti-malarial activity. This study scientifically validates the use of
      this plant in folk medicine. CONCLUSIONS: This study proves that Warburgia
      salutaris contains components (including iso-mukaadial acetate) that exhibit anti
      malarial activity and scientifically validates the use of this plant in folk
      medicine.

PMID- 30111330
TI  - Specialist training aspirations of junior doctors in Sierra Leone: a qualitative
      follow-up study.
AB  - BACKGROUND: Sierra Leone is pursuing multiple initiatives to establish in-country
      postgraduate medical education (PGME), as part of national efforts to strengthen
      the health workforce. This paper explored the career preferences of junior
      doctors in Sierra Leone; and the potential benefits and challenges with regards
      to the development of PGME locally. METHODS: Junior doctors (n = 15) who had
      graduated from the only medical school in Sierra Leone were purposively sampled
      based on maximum variation (e.g. men/women, years of graduation). In-depth
      interviews were conducted in October 2013, and digital diaries and two follow-up
      interviews were used to explore their evolving career aspirations until November
      2016. Additionally, 16 semi-structured interviews with key informants were held
      to gather perspectives on the development of PGME locally. Results were
      thematically analysed. RESULTS: All junior doctors interviewed intended to pursue
      PGME with the majority wanting primarily a clinical career. Half were interested
      in also gaining a public health qualification. Major factors influencing career
      preferences included: prior exposure, practical (anticipated job content),
      personal considerations (individual interests), financial provision, and
      contextual (aspirations to help address certain health needs). Majority of
      doctors considered West Africa but East and South Africa were also location
      options for clinical PGME. Several preferred to leave the African continent to
      pursue PGME. Factors influencing decision-making on location were: financial
      (scholarships), practical (availability of preferred specialty), reputation
      (positive and negative), and social (children). Key informants viewed the
      potential benefits of expanding PGME in Sierra Leone as: cost-effectiveness
      (compared to overseas specialist training), maintaining service delivery during
      training years, decreasing loss of doctors (some decide not to return after
      gaining their specialist degree abroad), and enhancing quality control and
      academic culture of the local medical school. Major perceived challenges were
      capacity constraints, especially the dearth of specialists required to achieve
      training programme accreditation. CONCLUSIONS: This study has provided an insight
      into the career preferences of junior doctors in Sierra Leone. It is timely as
      there is increasing political and professional momentum to expand PGME locally.
      Findings may guide those involved in this PGME expansion in terms of how possibly
      to influence junior doctors in their career decision-making.

PMID- 30111332
TI  - Comprehensive gene expression profiling identifies distinct and overlapping
      transcriptional profiles in non-specific interstitial pneumonia and idiopathic
      pulmonary fibrosis.
AB  - BACKGROUND: The clinical-radiographic distinction between idiopathic pulmonary
      fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) is challenging. We
      sought to investigate the gene expression profiles of IPF and NSIP vs. normal
      controls. METHODS: Gene expression from explanted lungs of patients with IPF (n =
      22), NSIP (n = 10) and from normal controls (n = 11) was assessed. Microarray
      analysis included Significance Analysis of Microarray (SAM), Ingenuity Pathway,
      Gene-Set Enrichment and unsupervised hierarchical clustering analyses.
      Immunohistochemistry and serology of proteins of interest were conducted.
      RESULTS: NSIP cases were significantly enriched for genes related to mechanisms
      of immune reaction, such as T-cell response and recruitment of leukocytes into
      the lung compartment. In IPF, in contrast, these involved senescence, epithelial
      to-mesenchymal transition, myofibroblast differentiation and collagen deposition.
      Unlike the IPF group, NSIP cases exhibited a strikingly homogenous gene
      signature. Clustering analysis identified a subgroup of IPF patients with
      intermediate and ambiguous expression of SAM-selected genes, with the interesting
      upregulation of both NSIP-specific and senescence-related genes.
      Immunohistochemistry for p16, a senescence marker, on fibroblasts differentiated
      most IPF cases from NSIP. Serial serum levels of periostin, a senescence
      effector, predicted clinical progression in a cohort of patients with IPF.
      CONCLUSIONS: Comprehensive gene expression profiling in explanted lungs
      identifies distinct transcriptional profiles and differentially expressed genes
      in IPF and NSIP, supporting the notion of NSIP as a standalone condition.
      Potential gene and protein markers to discriminate IPF from NSIP were identified,
      with a prominent role of senescence in IPF. The finding of a subgroup of IPF
      patients with transcriptional features of both NSIP and senescence raises the
      hypothesis that "senescent" NSIP may represent a risk factor to develop
      superimposed IPF.

PMID- 30111331
TI  - Getting value from the waste: recombinant production of a sweet protein by
      Lactococcus lactis grown on cheese whey.
AB  - BACKGROUND: Recent biotechnological advancements have allowed for the adoption of
      Lactococcus lactis, a typical component of starter cultures used in food
      industry, as the host for the production of food-grade recombinant targets. Among
      several advantages, L. lactis has the important feature of growing on lactose,
      the main carbohydrate in milk and a majoritarian component of dairy wastes, such
      as cheese whey. RESULTS: We have used recombinant L. lactis NZ9000 carrying the
      nisin inducible pNZ8148 vector to produce MNEI, a small sweet protein derived
      from monellin, with potential for food industry applications as a high intensity
      sweetener. We have been able to sustain this production using a medium based on
      the cheese whey from the production of ricotta cheese, with minimal pre-treatment
      of the waste. As a proof of concept, we have also tested these conditions for the
      production of MMP-9, a protein that had been previously successfully obtained
      from L. lactis cultures in standard growth conditions. CONCLUSIONS: Other than
      presenting a new system for the recombinant production of MNEI, more compliant
      with its potential applications in food industry, our results introduce a
      strategy to valorize dairy effluents through the synthesis of high added value
      recombinant proteins. Interestingly, the possibility of using this whey-derived
      medium relied greatly on the choice of the appropriate codon usage for the target
      gene. In fact, when a gene optimized for L. lactis was used, the production of
      MNEI proceeded with good yields. On the other hand, when an E. coli optimized
      gene was employed, protein synthesis was greatly reduced, to the point of being
      completely abated in the cheese whey-based medium. The production of MMP-9 was
      comparable to what observed in the reference conditions.

PMID- 30111333
TI  - A feasibility study of a mobile phone supported family-centred ADL intervention,
      F@ceTM, after stroke in Uganda.
AB  - BACKGROUND: There is a lack of evidence-based health services to reduce the
      impact of stroke in low-income countries at a personal, family or community
      level. The aim was to evaluate the feasibility of: i) a mobile phone supported
      family-centred intervention (F@ceTM), and ii) the study design for evaluating the
      effects of the intervention on the perceived impact of stroke; perceived
      participation in everyday life; and self-efficacy in everyday activities amongst
      persons with stroke and their families in Uganda. METHODS: The study comprised a
      pre-post design with an intervention group (IG) receiving the F@ceTM and a
      control group (CG). The inclusion criteria's were: a) confirmed stroke diagnosis,
      b) access to and ability to use a mobile phone, c) ability to communicate in
      English and/or Luganda, d) > 18 years, e) residents in Kampala, and f) a Modified
      Rankin Scale level 2 to 4. The aim of the F@ceTM was to increase functioning in
      daily activities for persons living with the consequences of stroke, and
      participation in everyday life for persons with stroke and their families. The
      F@ceTM was an eight-week family-centred intervention, which entailed goal setting
      and problem-solving strategies, daily reminders and self-rated follow-ups of
      performance by short message service (SMS). Data were collected in the
      participants' home environment at baseline and after eight weeks. Data on
      acceptability of the F@ceTM and study procedures were collected by log-books and
      the responses of the SMS follow ups on the server. The primary outcomes were
      performance and satisfaction of valued daily activities in everyday life using
      the Canadian Occupational Performance Measure (COPM), self-efficacy in
      performance of activities in daily life. RESULTS: The IG comprised n = 13 and the
      CG n = 15. There were differences between the IG and CG in changes between
      baseline and follow-up in the primary outcomes COPM (performance component) and
      self-efficacy in favour of F@ceTM. Overall with minor modifications the
      intervention and the study design were feasible for all participants involved.
      CONCLUSION: The results support the need for further research to rigorously
      evaluate the effects of F@ceTM since the intervention appears to be feasible for
      persons with stroke and their family members.

PMID- 30111336
TI  - Primary angiosarcoma arising in an angiomyolipoma of the kidney: case report and
      literature review.
AB  - BACKGROUND: Primary angiosarcoma of the kidney is a rare and aggressive malignant
      tumor presenting with a recognizable vascular differentiation. Its prognosis is
      fatal and the pathogenesis remains unclear. Renal angiomyolipoma is a relatively
      infrequent renal cortical neoplasm and is composed of variable proportions of
      adipose tissue, spindle cells, epithelioid smooth muscle cells and abnormal thick
      walled blood vessels. CASE PRESENTATION: Here, we reported a case in which a 64
      year-old woman presenting with the chief complaint of a progressively enlarged
      mass in the left abdomen. Abdominal computed tomography confirmed presence of a
      tumor measuring 18 cm * 11 cm in the left posterior renal fascia. Microscopic
      examination and immunohistochemical staining confirmed co-existence of
      angiomyolipoma and angiosarcoma. Furthermore, the two components interspersed
      with each other and there were transitional zones between them. CONCLUSIONS: In
      this case, we described for the first time a primary renal angiosarcoma possibly
      arising in a pre-existing angiomyolipoma of the kidney.

PMID- 30111335
TI  - Reproductive health problems in rural South African young women: risk behaviour
      and risk factors.
AB  - BACKGROUND: South African young women continue to be vulnerable, with high
      prevalence of teenage pregnancy, HIV, sexually transmitted infections (STIs) and
      female genital schistosomiasis (FGS). This study seeks to examine the underlying
      factors that may be associated with these four adverse reproductive health
      outcomes. METHODS: In a cross-sectional study of 1413 sexually active of young
      women, we explored these four adverse reproductive health outcomes by considering
      socio-demographic factors, socio-economic factors, sexual risk behaviour,
      substance abuse and knowledge about reproductive health by using a questionnaire.
      Consenting participants were asked about previous pregnancies and were tested for
      HIV, STIs and FGS. Multivariable regression analyses were used to explore the
      factors associated with these four reproductive health outcomes. RESULTS: 1.
      Early pregnancy: Among the young women, 44.4% had already been pregnant at least
      once. Associated factors were hormonal contraceptives, (adjusted odds ratio
      (AOR): 17.94, 95% confidence interval (CI): 12.73-25.29), and sexual debut < 16
      years (AOR: 3.83, 95% CI: 2.68-5.47). Living with both parents (AOR 0.37, 95% CI:
      0.25-0.57) and having a steady partner (AOR: 0.43, 95% CI: 0.24-0.76) were
      identified as protective factors against pregnancy. 2. HIV: HIV prevalence was
      17.1%. The odds of having HIV were higher in intergenerational (AOR: 2.06, 95%
      CI: 1.05-4.06) and intragenerational relationships (AOR: 1.51 95% CI: 1.06-2.15),
      compared to age-homogenous relationships. Other associated factors were: condom
      use (AOR: 1.60, 95% CI: 1.16-2.20), number of times treated for an STI (AOR:
      1.32, 95% CI: 1.02-1.71), and total number of partners (AOR: 1.14, 95% CI: 1.03
      1.28). 3. STIs: Participants who had at least one STI (40.5%) were associated
      with total partner number (AOR 1.17, 95% CI: 1.06-1.30), and testing HIV positive
      (AOR: 1.88, 95% CI 1.41-2.50). 4. FGS: FGS prevalence (19.7%) was associated with
      previous anti-schistosomal treatment (AOR: 2.18, 95% CI: 1.57-3.05). CONCLUSION:
      There is a high prevalence of pregnancy, HIV, STIs and FGS among sexually active
      young women in rural KwaZulu-Natal. Multidisciplinary approaches are urgently
      needed for educational and health literacy programs prior to sexual debut, and
      health care facilities, which should be made accessible for young women.

PMID- 30111334
TI  - Miglustat in Niemann-Pick disease type C patients: a review.
AB  - OBJECTIVE: Niemann-Pick disease type C (NP-C) is a rare, autosomal recessive,
      neurodegenerative disease associated with a wide variety of progressive
      neurological manifestations. Miglustat is indicated for the treatment of
      progressive neurological manifestations in both adults and children. Since
      approval in 2009 there has been a vast growth in clinical experience with
      miglustat. The effectiveness of miglustat has been assessed using a range of
      measures. METHODS: Comprehensive review of published data from studies of
      cellular neuropathological markers and structural neurological indices in the
      brain, clinical impairment/disability, specific clinical neurological
      manifestations, and patient survival. RESULTS: Cranial diffusion tensor imaging
      and magnetic resonance spectroscopy studies have shown reduced levels of choline
      (a neurodegeneration marker), and choline/N-acetyl aspartate ratio (indicating
      increased neuronal viability) in the brain during up to 5 years of miglustat
      therapy, as well as a slowing of reductions in fractional anisotropy (an
      axonal/myelin integrity marker). A 2-year immunoassay study showed significant
      reductions in CSF-calbindin during treatment, indicating reduced cerebellar
      Purkinje cell loss. Magnetic resonance imaging studies have demonstrated a
      protective effect of miglustat on cerebellar and subcortical structure that
      correlated with clinical symptom severity. Numerous cohort studies assessing core
      neurological manifestations (impaired ambulation, manipulation, speech,
      swallowing, other) using NP-C disability scales indicate neurological
      stabilization over 2-8 years, with a trend for greater benefits in patients with
      older (non-infantile) age at neurological onset. A randomized controlled trial
      and several cohort studies have reported improvements or stabilization of
      saccadic eye movements during 1-5 years of therapy. Swallowing was also shown to
      improve/remain stable during the randomized trial (up to 2 years), as well as in
      long-term observational cohorts (up to 6 years). A meta-analysis of dysphagia - a
      potent risk factor for aspiration pneumonia and premature death in NP-C -
      demonstrated a survival benefit with miglustat due to improved/stabilized
      swallowing function. CONCLUSIONS: The effects of miglustat on neurological NP-C
      manifestations has been assessed using a range of approaches, with benefits
      ranging from cellular changes in the brain through to visible clinical
      improvements and improved survival.

PMID- 30111338
TI  - Anti-inflammatory signaling by mammary tumor cells mediates prometastatic
      macrophage polarization in an innovative intraductal mouse model for triple
      negative breast cancer.
AB  - BACKGROUND: Murine breast cancer models relying on intraductal tumor cell
      inoculations are attractive because they allow the study of breast cancer from
      early ductal carcinoma in situ to metastasis. Using a fully immunocompetent 4T1
      based intraductal model for triple-negative breast cancer (TNBC) we aimed to
      investigate the immunological responses that guide such intraductal tumor
      progression, focusing on the prominent role of macrophages. METHODS: Intraductal
      inoculations were performed in lactating female mice with luciferase-expressing
      4T1 mammary tumor cells either with or without additional RAW264.7 macrophages,
      mimicking basal versus increased macrophage-tumor cell interactions in the ductal
      environment. Imaging of 4T1-derived luminescence was used to monitor primary
      tumor growth and metastases. Tumor proliferation, hypoxia, disruption of the
      ductal architecture and tumor immune populations were determined
      immunohistochemically. M1- (pro-inflammatory) and M2-related (anti-inflammatory)
      cytokine levels were determined by Luminex assays and ELISA to investigate the
      activation state of the macrophage inoculum. Levels of the metastatic proteins
      matrix metalloproteinase 9 (MMP-9) and vascular endothelial growth factor (VEGF)
      as well as of the immune-related disease biomarkers chitinase 3-like 1 (CHI3L1)
      and lipocalin 2 (LCN2) were measured by ELISA to evaluate disease progression at
      the protein level. RESULTS: Mice intraductally co-injected with macrophages
      showed severe splenomegaly with faster ductal breakthrough of tumor cells and
      increased metastases in axillary lymph nodes and lungs. These mice showed higher
      M1-related cytokines in the early disease stages (at 1 to 3 weeks post
      inoculation) due to the pro-inflammatory nature of RAW264.7 macrophages with
      increased Ly6G-positive neutrophils and decreased anti-inflammatory macrophages
      in the tumor microenvironment. However, upon metastasis (at 5 weeks post
      inoculation), a prominent increase in M2-related cytokine levels was detected and
      established a tumor microenvironment with similar immune populations and cytokine
      responses as in mice which received only 4T1 tumor cells. The observed tumor
      associated immune responses and the increased metastasis were associated with
      significantly induced local and systemic levels of MMP-9, VEGF, CHI3L1 and LCN2.
      CONCLUSIONS: The current experimental study with an innovative immunocompetent
      intraductal model for TNBC pinpoints towards a metastasis-supporting M1 to M2
      macrophage polarization in the mammary ducts mediated by 4T1-derived signaling.
      We propose to explore this process as immunotherapeutic target.

PMID- 30111337
TI  - Validation of wearable visual feedback for retraining foot progression angle
      using inertial sensors and an augmented reality headset.
AB  - BACKGROUND: Gait retraining interventions using real-time biofeedback have been
      proposed to alter the loading across the knee joint in patients with knee
      osteoarthritis. Despite the demonstrated benefits of these conservative
      treatments, their clinical adoption is currently obstructed by the high
      complexity, spatial demands, and cost of optical motion capture systems. In this
      study we propose and evaluate a wearable visual feedback system for gait
      retraining of the foot progression angle (FPA). METHODS: The primary components
      of the system are inertial measurement units, which track the human movement
      without spatial limitations, and an augmented reality headset used to project the
      visual feedback in the visual field. The adapted gait protocol contained five
      different target angles ranging from 15 degrees toe-out to 5 degrees toe-in.
      Eleven healthy participants walked on an instrumented treadmill, and the protocol
      was performed using both an established laboratory visual feedback driven by
      optical motion capture, and the proposed wearable system. RESULTS AND
      CONCLUSIONS: The wearable system tracked FPA with an accuracy of 2.4 degrees RMS
      and ICC=0.94 across all target angles and subjects, when compared to an optical
      motion capture reference. In addition, the effectiveness of the biofeedback,
      reflected by the number of steps with FPA value +/-2 degrees from the target, was
      found to be around 50% in both wearable and laboratory approaches. These findings
      demonstrate that retraining of the FPA using wearable inertial sensing and visual
      feedback is feasible with effectiveness matching closely an established
      laboratory method. The proposed wearable setup may reduce the complexity of gait
      retraining applications and facilitate their transfer to routine clinical
      practice.

PMID- 30111339
TI  - Learning from the emergence of NIHR Collaborations for Leadership in Applied
      Health Research and Care (CLAHRCs): a systematic review of evaluations.
AB  - BACKGROUND: Collaborations for Leadership in Applied Health Research and Care
      (CLAHRCs) were funded by NIHR in England in 2008 and 2014 as partnerships between
      universities and surrounding health service organisations, focused on improving
      the quality of healthcare through the conduct and application of applied health
      research. The aim of this review is to synthesise learning from evaluations of
      the CLAHRCs. METHODS: Fifteen databases including CINAHL, MEDLINE, EMBASE and
      PsycINFO were searched to identify any evaluations of CLAHRCs. Current and
      archived CLAHRC websites and the reference lists of retrieved articles were
      scanned to identify any additional evaluations. Searches were restricted to
      English language only. Any publications from evaluations of the CLAHRCs were
      eligible for inclusion if they fulfilled at least one of three pre-specified
      inclusion criteria. A narrative synthesis was undertaken. RESULTS: Twenty-six
      evaluations (reported in 37 papers) were deemed eligible for inclusion.
      Evaluations focused on describing and exploring the formative partnerships,
      vision, values, structures and processes of CLAHRCs; the nature and role of
      boundaries; the deployment of knowledge brokers and hybrid roles to support
      knowledge mobilisation; patient and public involvement; and capacity building.
      The relative lack of data about the early impact of CLAHRCs on health care
      provision or outcomes is notable. CONCLUSIONS: Much of the evaluative focus on
      CLAHRCs has been on how they have been organised and on the development of theory
      around their emergent properties. Evidence is lacking on the impact of CLAHRCs
      particularly in relation to the knowledge mobilisation processes and practices
      adopted. Further evaluation of CLAHRCs and other similar research and practice
      partnerships is warranted and should focus on which knowledge mobilisation
      approaches work where, how and why. TRIAL REGISTRATION: PROSPERO (Registration
      number: CRD42016042945 ).

PMID- 30111340
TI  - Accurate, strong, and stable reporting of choroid plexus epithelial cells in
      transgenic mice using a human transthyretin BAC.
AB  - BACKGROUND: Choroid plexus epithelial cells express high levels of transthyretin,
      produce cerebrospinal fluid and many of its proteins, and make up the blood
      cerebrospinal fluid barrier. Choroid plexus epithelial cells are vital to brain
      health and may be involved in neurological diseases. Transgenic mice containing
      fluorescent and luminescent reporters of these cells would facilitate their study
      in health and disease, but prior transgenic reporters lost expression over the
      early postnatal period. METHODS: Human bacterial artificial chromosomes in which
      the transthyretin coding sequence was replaced with DNA for tdTomato or
      luciferase 2 were used in pronuclear injections to produce transgenic mice. These
      mice were characterized by visualizing red fluorescence, immunostaining, real
      time reverse transcription polymerase chain reaction, and luciferase enzyme
      assay. RESULTS: Reporters were faithfully expressed in cells that express
      transthyretin constitutively, including choroid plexus epithelial cells, retinal
      pigment epithelium, pancreatic islets, and liver. Expression of tdTomato in
      choroid plexus began at the appropriate embryonic age, being detectable by E11.5.
      Relative levels of tdTomato transcript in the liver and choroid plexus paralleled
      relative levels of transcripts for transthyretin. Expression remained robust over
      the first postnatal year, although choroid plexus transcripts of tdTomato
      declined slightly with age whereas transthyretin remained constant. TdTomato
      expression patterns were consistent across three founder lines, displayed no sex
      differences, and were stable across several generations. Two of the tdTomato
      lines were bred to homozygosity, and homozygous mice are healthy and fertile. The
      usefulness of tdTomato reporters in visualizing and analyzing live Transwell
      cultures was demonstrated. Luciferase activity was very high in homogenates of
      choroid plexus and continued to be expressed through adulthood. Luciferase also
      was detectable in eye and pancreas. CONCLUSIONS: Transgenic mice bearing
      fluorescent and luminescent reporters of transthyretin should prove useful for
      tracking transplanted choroid plexus epithelial cells, for purifying the cells,
      and for reporting their derivation from stem cells. They also should prove useful
      for studying transthyretin synthesis by other cell types, as transthyretin has
      been implicated in many functions and conditions, including clearance of beta
      amyloid peptides associated with Alzheimer's disease, heat shock in neurons,
      processing of neuropeptides, nerve regeneration, astrocyte metabolism, and
      transthyretin amyloidosis.

PMID- 30111342
TI  - How do external factors contribute to the hypocoagulative state in trauma-induced
      coagulopathy? - In vitro analysis of the lethal triad in trauma.
AB  - BACKGROUND: External factors following trauma and iatrogenic intervention
      influence blood coagulation and particularly clot formation. In particular, three
      external factors (in detail dilution via uncritical volume replacement, acidosis
      and hypothermia), in combination, referred to as the "lethal triad",
      substantially aggravate the hypocoagulative state after trauma. Contribution of
      these external factors to the resulting hypocoagulative state in trauma and
      especially their influence on primary haemostasis has still not been investigated
      systematically. This study aims to assess this contribution to the aggravating
      hypocoagulative state in trauma-induced coagulopathy (TIC) using an in vitro
      simulation assay. Emphasis is given to platelet contribution to clot formation
      and to the investigation of how platelet activation alters under the respective
      conditions. METHODS: To simulate the conditions of lethal triad in vitro, whole
      blood samples taken from five healthy volunteers were introduced to the
      respective conditions. Besides standard coagulation testing, thrombelastometric
      analysis and differentiated platelet mapping were performed. RESULTS: All three
      simulated conditions induced significant impairments of clot formation (clot
      formation time, CFT; alpha -angle) and propagation (maximum clot firmness, MCF;
      Diameter A5-A25), with the highest impact under hypothermia and dilution.
      Consistently, lethal triad resulted in an additive effect of all conditions. None
      of the simulated conditions induced a statistically relevant change in
      coagulation initiation assessed by EXTEM and FIBTEM thrombelastometry. Platelet
      contribution to clot formation decreased gradually under the respective
      conditions, reaching statistical significance for simulated dilution, and
      attaining its greatest extent under the conditions of lethal triad
      (Deltatrias/baseline 0.59; p = 0.01). Consistent, reduced CD62 expression levels
      were observed under experimental acidosis (Deltaacidosis/baseline 0.32; p =
      0.006), dilution (Deltadilution/baseline 0.34; p = 0.01) and lethal triad
      (Deltalethal triad/baseline 0.24; p = 0.01). CONCLUSION: The respective external
      factors of lethal triad play a pivotal role in the development of coagulopathy,
      essentially influencing the kinetics of clot formation, and to a varying extent
      clot diameter, as measured by thrombelastometry. Moreover, impairment of platelet
      function under the conditions of lethal triad plays a key role in the
      pathophysiology of TIC, resulting in reduced responsiveness to stimulation with
      ADP that might also be present after trauma. Our data indicate that impairment of
      primary haemostasis contribute to the hypocoagulative state in TIC after trauma
      aggravated by external factors of lethal triad.

PMID- 30111341
TI  - Effect of procalcitonin-guided antibiotic treatment on clinical outcomes in
      intensive care unit patients with infection and sepsis patients: a patient-level
      meta-analysis of randomized trials.
AB  - BACKGROUND: The clinical utility of serum procalcitonin levels in guiding
      antibiotic treatment decisions in patients with sepsis remains unclear. This
      patient-level meta-analysis based on 11 randomized trials investigates the impact
      of procalcitonin-guided antibiotic therapy on mortality in intensive care unit
      (ICU) patients with infection, both overall and stratified according to sepsis
      definition, severity, and type of infection. METHODS: For this meta-analysis
      focusing on procalcitonin-guided antibiotic management in critically ill patients
      with sepsis of any type, in February 2018 we updated the database of a previous
      individual patient data meta-analysis which was limited to patients with
      respiratory infections only. We used individual patient data from 11 trials that
      randomly assigned patients to receive antibiotics based on procalcitonin levels
      (the "procalcitonin-guided" group) or the current standard of care (the
      "controls"). The primary endpoint was mortality within 30 days. Secondary
      endpoints were duration of antibiotic treatment and length of stay. RESULTS:
      Mortality in the 2252 procalcitonin-guided patients was significantly lower
      compared with the 2230 control group patients (21.1% vs 23.7%; adjusted odds
      ratio 0.89, 95% confidence interval (CI) 0.8 to 0.99; p = 0.03). These effects on
      mortality persisted in a subgroup of patients meeting the sepsis 3 definition and
      based on the severity of sepsis (assessed on the basis of the Sequential Organ
      Failure Assessment (SOFA) score, occurrence of septic shock or renal failure, and
      need for vasopressor or ventilatory support) and on the type of infection
      (respiratory, urinary tract, abdominal, skin, or central nervous system), with
      interaction for each analysis being > 0.05. Procalcitonin guidance also
      facilitated earlier discontinuation of antibiotics, with a reduction in treatment
      duration (9.3 vs 10.4 days; adjusted coefficient -1.19 days, 95% CI -1.73 to 
      0.66; p <  0.001). CONCLUSION: Procalcitonin-guided antibiotic treatment in ICU
      patients with infection and sepsis patients results in improved survival and
      lower antibiotic treatment duration.

PMID- 30111343
TI  - Airway and ventilation management during cardiopulmonary resuscitation and after
      successful resuscitation.
AB  - After cardiac arrest a combination of basic and advanced airway and ventilation
      techniques are used during cardiopulmonary resuscitation (CPR) and after a return
      of spontaneous circulation (ROSC). The optimal combination of airway techniques,
      oxygenation and ventilation is uncertain. Current guidelines are based
      predominantly on evidence from observational studies and expert consensus; recent
      and ongoing randomised controlled trials should provide further information. This
      narrative review describes the current evidence, including the relative roles of
      basic and advanced (supraglottic airways and tracheal intubation) airways,
      oxygenation and ventilation targets during CPR and after ROSC in adults. Current
      evidence supports a stepwise approach to airway management based on patient
      factors, rescuer skills and the stage of resuscitation. During CPR, rescuers
      should provide the maximum feasible inspired oxygen and use waveform capnography
      once an advanced airway is in place. After ROSC, rescuers should titrate inspired
      oxygen and ventilation to achieve normal oxygen and carbon dioxide targets.

PMID- 30111344
TI  - European Reference Network For Rare Vascular Diseases (VASCERN) Outcome Measures
      For Hereditary Haemorrhagic Telangiectasia (HHT).
AB  - Hereditary haemorrhagic telangiectasia (HHT) is a multisystemic vascular
      dysplasia that leads to nosebleeds, anaemia due to blood loss, and arteriovenous
      malformations (AVMs) in organs such as the lungs, liver and brain. HHT is
      estimated to affect 85,000 European citizens, but most health care providers have
      limited prior HHT exposure or training.Outcome Measures were developed and
      implemented by the HHT Working Group of the European Reference Network for Rare
      Vascular Diseases (VASCERN), in order to maximise the number of patients
      receiving good care. The measures specifically target areas where optimal
      management reduces morbidity and mortality in HHT patients, and were designed to
      be robust to emerging new evidence. Thresholds are the percentage of patients in
      particular settings who have been recommended screening, or provided with written
      advice. The 5 Outcome Measures cover (1) pulmonary AVM screening; (2) written
      nosebleed advice, (3) assessment of iron deficiency; (4) antibiotic prophylaxis
      prior to dental and surgical procedures for patients with pulmonary AVMs, and (5)
      written advice on pregnancy. They are not a blueprint for detailed HHT
      management, but are suitable for all clinicians to be aware of and implement.In
      summary, these 5 Outcome Measures provide metrics to identify healthcare
      providers of good care, and encourage care improvement by all healthcare
      providers.

PMID- 30111346
TI  - Ethnomedicinal applications of animal species by the local communities of Punjab,
      Pakistan.
AB  - BACKGROUND: Different species of animals are being utilized in traditional
      therapies by various cultures for a long time and such uses still exist in folk
      medicine. The present study aimed to document animal-based traditional therapies
      used by the local communities of Jhelum and Lahore districts of the Punjab
      province, Pakistan. METHODS: Field surveys were conducted in 2015-2016 in six
      different sites of the study areas. Data were collected through semi-structured
      interviews and face to face conversation with local informants. RESULTS: The
      ethnomedicinal uses of 57 species of animals including mammals, birds, fish,
      reptiles, amphibian, and invertebrates (30, 25, 25, 7, 3.5, and 3.5%,
      respectively) were documented. Meat, oil, brain, fats, milk, eggs, and skin were
      the most utilized body parts. Ovis orientalis punjabiensis, Francolinus
      francolinus, Sperata sarwari, Channa punctata, Oreochromis niloticus,
      Ctenopharyngodon idella, Cyprinus carpio, Labeo rohita, and Carassius auratus
      were reported for the first time to treat human diseases, i.e., allergy,
      epilepsy, fever, joint pain, and backache, to act as aphrodisiac, and to enhance
      memory. Streptopelia decaocto and S. tranquebarica were the most frequently
      utilized species with highest frequency of citation (32 for each). Columba livia
      depicted highest fidelity level and used value of 92.86% and 0.89, respectively.
      CONCLUSIONS: Being agro-pastoralists, the inhabitants of Jhelum possess more
      traditional knowledge compared to Lahore. The present study could be important
      for conservation and sustainable use of animal biodiversity in this region.
      Additionally, detailed study on chemical profiling and bioactivities may lead to
      animal-based novel drug discovery.

PMID- 30111345
TI  - Cell type-specific CLIP reveals that NOVA regulates cytoskeleton interactions in
      motoneurons.
AB  - BACKGROUND: Alternative RNA processing plays an essential role in shaping cell
      identity and connectivity in the central nervous system. This is believed to
      involve differential regulation of RNA processing in various cell types. However,
      in vivo study of cell type-specific post-transcriptional regulation has been a
      challenge. Here, we describe a sensitive and stringent method combining genetics
      and CLIP (crosslinking and immunoprecipitation) to globally identify regulatory
      interactions between NOVA and RNA in the mouse spinal cord motoneurons. RESULTS:
      We developed a means of undertaking motoneuron-specific CLIP to explore
      motoneuron-specific protein-RNA interactions relative to studies of the whole
      spinal cord in mouse. This allowed us to pinpoint differential RNA regulation
      specific to motoneurons, revealing a major role for NOVA in regulating
      cytoskeleton interactions in motoneurons. In particular, NOVA specifically
      promotes the palmitoylated isoform of the cytoskeleton protein Septin 8 in
      motoneurons, which enhances dendritic arborization. CONCLUSIONS: Our study
      demonstrates that cell type-specific RNA regulation is important for fine tuning
      motoneuron physiology and highlights the value of defining RNA processing
      regulation at single cell type resolution.

PMID- 30111347
TI  - EHAC medical working group best practice advice on the role of air rescue and pre
      hospital critical care at major incidents.
AB  - BACKGROUND: Helicopter EMS (HEMS) teams may perform a variety of clinical,
      managerial and transport functions during major incident management. Despite
      national and international variations in HEMS systems, the rapid delivery of HEMS
      personnel with advanced skills in major incident management and clinical scene
      leadership has been crucial to the delivery of an effective medical response at
      previous incidents. This document outlines the Best Practice Advice of the
      European HEMS and Air Ambulance Committee (EHAC) Medical Working Group on how
      HEMS and Pre Hospital Critical Care teams may maximise the positive impact of
      their resources in the event of Major Incidents. METHODS: Narrative literature
      review and expert consensus. RESULTS: To ensure a safe, coordinated and effective
      response, HEMS teams require suitable, proportionate and up to date major
      incident plans that are integrated into the major incident plans of other
      regional emergency and healthcare services. Role specific protocols, training and
      equipment should be adapted to the expected HEMS role in the major incident plan
      and likely regional threats. System and incident factors will influence HEMS
      utilisation during the major incident response and can include patient and staff
      transfer, equipment resupply, aerial assessment, search and rescue, clinical
      leadership and advanced care. During the recovery phase of a major incident there
      is a need to ensure restoration of conventional service and address the welfare
      of involved HEMS personnel. Standardised reporting of major incidents is strongly
      recommended for clinical governance, legal and research reasons. CONCLUSIONS: The
      rapid delivery of HEMS personnel with advanced skills in Major Incident
      management and clinical scene leadership is crucial to the delivery of an
      effective medical response at Major Incidents.

PMID- 30111348
TI  - Late effects in survivors of childhood acute lymphoblastic leukemia in the
      context of selected gene polymorphisms.
AB  - BACKGROUND: It has been shown that approximately half of survivors of childhood
      acute lymphoblastic leukemia (ALL) have symptomatic late effects (LE) that may be
      severe or life-threatening. The aim of our study was to assess the health status
      of childhood ALL survivors after over 10 years of follow-up and to assess its
      relationships with gene polymorphisms, numbers and types of LEs, as well as with
      intensity of chemotherapy and cranial radiotherapy (CRT). METHODS: We conducted a
      telephone survey in 125 ALL survivors (median time from completion of treatment
      was 12 years) and compared the results with those obtained in our previous study.
      Most of the patients were followed-up by local providers. RESULTS: The prevalence
      of LEs of approximately 50% was similar in both study groups. More than one LE
      was found in almost 25% of patients. Endocrine LEs were less frequent than in our
      previous study (44% vs 22%), probably due to underdiagnosis. The prevalence of
      hepatitis B/C decreased from 30%/50 to 18% (counted together), and prevalence of
      neurologic LEs decreased from 18 to 6%. The increase in the rate of second
      malignancies was not significant (2% vs. 3%). Sixty four percent of patients
      continued their education at the time of the study. Approximately 51% of ALL
      survivors who have completed their education by the time of the study had no
      permanent employment, including 4 mothers of infants and 3 persons qualified for
      a disability living allowance. These employment problems may have been due to
      cognitive impairment. The offspring of the ALL survivors included 11 children,
      all of them healthy. Further analysis showed higher prevalence of hepatitis in
      patients treated with CRT (p = 0.0001). Genetic studies revealed higher
      prevalence of hepatitis in patients homozygous for the rs9939609A variant of the
      FTO gene compared with other patients (p = 0.03). Moreover, wild-type rs1137101
      polymorphism (Q223R) of the and leptin receptor gene was more frequent in
      patients with psychological LEs (p = 0.03). CONCLUSIONS: The prevalence of LEs in
      ALL survivors is of key importance. The transition of childhood ALL survivors
      from pediatric to adult care should be urgently improved to maintain continued
      follow-up provide high-quality care. TRIAL REGISTRATION: Bioethics Committee of
      the Jagiellonian University approved the study protocol. Registration number:
      KBET/113/B/2006.

PMID- 30111350
TI  - Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in two
      young children: the importance of an early diagnosis.
AB  - BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS)
      syndrome is a serious life-treating condition characterized by skin eruption,
      fever, haematologic abnormalities, and multi-organ involvement that can be fatal
      if unrecognized, especially in patients with liver failure. Diagnosis may be
      difficult because it is rarely described in children and can mimic many different
      conditions. CASE PRESENTATION: We report two cases of DRESS syndrome due to
      prolonged antibiotic treatment in young children in whom recovery occurred
      following different therapeutic approaches. A previously healthy 5-year-old boy
      had been receiving intravenous vancomycin for right wrist and left elbow
      osteomyelitis and developed DRESS syndrome on day 30. The patient achieved a
      complete resolution of all symptoms with pulse methylprednisolone followed by
      oral prednisone. A 4-year-old girl with cystic fibrosis, pancreatic
      insufficiency, chronic pulmonary colonization by Gram-positive bacteria admitted
      for pulmonary exacerbation was treated with intravenous piperacillin-tazobactam
      and tobramycin. After 14 days of treatment, she developed DRESS syndrome:
      antibiotic treatment was therefore stopped, and without any further therapy, a
      progressive resolution of the patient's clinical features was observed within 7
      days, while the normalization of laboratory abnormalities was achieved at 14
      days. CONCLUSIONS: Our cases highlight that paediatricians should be aware of the
      clinical presentations of and therapeutic approaches for DRESS syndrome,
      especially in children receiving long-term antibiotic treatment. The removal of
      the offending drug is crucial and may be the only life-saving measure. In more
      aggressive cases, corticosteroid or other immunosuppressive drugs should be
      considered to achieve the best outcome.

PMID- 30111349
TI  - Encephalopathies with intracranial calcification in children: clinical and
      genetic characterization.
AB  - BACKGROUND: We present a group of patients affected by a paediatric onset genetic
      encephalopathy with cerebral calcification of unknown aetiology studied with Next
      Generation Sequencing (NGS) genetic analyses. METHODS: We collected all clinical
      and radiological data. DNA samples were tested by means of a customized gene
      panel including fifty-nine genes associated with known genetic diseases with
      cerebral calcification. RESULTS: We collected a series of fifty patients. All
      patients displayed complex and heterogeneous phenotypes mostly including
      developmental delay and pyramidal signs and less frequently movement disorder and
      epilepsy. Signs of cerebellar and peripheral nervous system involvement were
      occasionally present. The most frequent MRI abnormality, beside calcification,
      was the presence of white matter alterations; calcification was localized in
      basal ganglia and cerebral white matter in the majority of cases. Sixteen out of
      fifty patients tested positive for mutations in one of the fifty-nine genes
      analyzed. In fourteen cases the analyses led to a definite genetic diagnosis
      while results were controversial in the remaining two. CONCLUSIONS: Genetic
      encephalopathies with cerebral calcification are usually associated to complex
      phenotypes. In our series, a molecular diagnosis was achieved in 32% of cases,
      suggesting that the molecular bases of a large number of disorders are still to
      be elucidated. Our results confirm that cerebral calcification is a good
      criterion to collect homogeneous groups of patients to be studied by exome or
      whole genome sequencing; only a very close collaboration between clinicians,
      neuroradiologists and geneticists can provide better results from these new
      generation molecular techniques.

PMID- 30111351
TI  - Novel clinicopathological and molecular characterization of metanephric adenoma:
      a study of 28 cases.
AB  - BACKGROUND: Metanephric adenoma is a rare, benign renal neoplasm with occasional
      misdiagnosis. However, its molecular characterization is not fully understood.
      METHODS: In this study, we use the hybrid capture-based Next-Generation
      Sequencing to sequence a panel of 295 well-established oncogene or tumor
      suppressor genes in 28 cases of MA patients in China. Novel clinicopathological
      markers associated with the mitogen-activated protein kinase (MAPK) pathway in
      metanephric adenoma were detected by immunohistochemistry. RESULTS: It was found
      that except for BRAF (22/28) mutations (c.1799 T > A, p.V600E), NF1 (6/28),
      NOTCH1 (5/28), SPEN (5/28), AKT2 (4/28), APC (4/28), ATRX (3/28), and ETV4 (3/28)
      mutations could also be detected. Meanwhile, a novel and rare gene fusion of
      STARD9-BRAF, CUX1-BRAF, and LOC100507389-BRAF was detected in one MA patient. In
      addition, although MEK phosphorylation was normally activated, the
      phosphorylation level of ERK was low in metanephric adenoma cases. Highly
      expressed p16 and DUSP6 may have contributed to these results, which maintained
      MA as a benign renal tumor. CONCLUSIONS: This study provides novel molecular and
      pathological markers for metanephric adenoma, which could improve its diagnosis
      and increase the understanding of its pathologic mechanism.

PMID- 30111352
TI  - HJURP promotes hepatocellular carcinoma proliferation by destabilizing p21 via
      the MAPK/ERK1/2 and AKT/GSK3beta signaling pathways.
AB  - BACKGROUND: Holliday junction recognition protein (HJURP) has been implicated in
      many cancers including hepatocellular carcinoma (HCC). However, the underlying
      mechanism by which HJURP promotes HCC cell proliferation remains unclear.
      METHODS: RT-qPCR and immunohistochemistry were used to detect HJURP expression in
      HCC and adjacent tumor tissues and HCC cell lines. The localization of p21 were
      determined by immunofluorescence and western blot. Co-immunoprecipitation and
      western blot were used to validate the p21 stability and signaling pathways
      affected by HJURP. The effects of HJURP on HCC cell proliferation were assessed
      both in vivo and in vitro. The ERK1/2 pathway inhibitor U0126 and AKT pathway
      agonist SC-79 were used to treat HCC cell lines for further mechanistic
      investigations. RESULTS: HJURP expression was higher in HCC tissues than in para
      tumor tissues. Moreover, ectopic HJURP expression facilitated the proliferation
      of HCC cells, whereas the depletion of HJURP resulted in decreased cell growth in
      vitro and in vivo. Furthermore, the effects of HJURP silencing were reversed by
      p21 knockdown. Likewise, p21 overexpression inhibited cell growth ability
      mediated by HJURP elevation. Mechanistically, HJURP destabilized p21 via the
      MAPK/ERK1/2 and AKT/GSK3beta pathways, which regulated the nucleus-cytoplasm
      translocation and ubiquitin-mediated degradation of p21. Clinically, high HJURP
      expression was correlated with unfavorable prognoses in HCC individuals.
      CONCLUSIONS: Our data revealed that HJURP is an oncogene that drives cell cycle
      progression upstream of p21 in HCC. These findings may provide a potential
      therapeutic and prognostic target for HCC.

PMID- 30111353
TI  - Characterization of vertigo and hearing loss in patients with Fabry disease.
AB  - BACKGROUND: Fabry Disease (FD) is an X-linked hereditary lysosomal storage
      disorder which leads to a multisystemic intralysosomal accumulation of
      globotriaosylceramid (Gb3). Besides prominent renal and cardiac organ
      involvement, patients commonly complain about vestibulocochlear symptoms like
      high-frequency hearing loss, tinnitus and vertigo. However, comprehensive data
      especially on vertigo remain scarce. The aim of this study was to examine the
      prevalence and characteristics of vertigo and hearing loss in patients with FD,
      depending on renal and cardiac parameters and get hints about the site and the
      pattern of the lesions. METHODS: Single-center study with 57 FD patients. Every
      patient underwent an oto-rhino-laryngological examination as well as
      videonystagmography and vestibular evoked myogenic potentials (VEMPs) and
      audiological measurements using pure tone audiometry and auditory brainstem
      response audiometry (ABR). Renal function was measured by eGFR, cardiac
      impairment was graduated by NYHA class. RESULTS: More than one out of three
      patients (35.1%) complained about hearing loss, 54.4% about vertigo and 28.1%
      about both symptom. In 74% a sensorineural hearing loss of at least 25 dB was
      found, ABR could exclude any retrocochlear lesion. Caloric testing showed
      abnormal values in 71.9%, VEMPs were pathological in 68%. A correlation between
      the side or the shape of hearing loss and pathological vestibular testing could
      not be revealed. CONCLUSIONS: Hearing loss and vertigo show a high prevalence in
      FD. While hearing loss seems due to a cochlear lesion, peripheral vestibular as
      well as central nervous pathologies cause vertigo. Thus, both the site of lesion
      and the pathophysiological patterns seem to differ.

PMID- 30111354
TI  - Triptolide inhibits Epstein-Barr nuclear antigen 1 expression by increasing
      sensitivity of mitochondria apoptosis of nasopharyngeal carcinoma cells.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is widely found in nasopharyngeal carcinoma
      (NPC) tissue and associated with poor prognosis of patients. EBV nuclear antigen
      1 (EBNA1) is expressed in all NPC tumors and plays multiple biological roles in
      both virus and host cells. Triptolide is a natural product extracted from
      Tripterygium and shows anti-cancer activities. The goal of this work was to
      illustrate the anti-cancer effect of triptolide and elucidate a novel anti
      apoptotic mechanism of EBNA1 in NPC cells encountered with triptolide. METHODS:
      In the present study, a CCK-8 assay was used to analyze the proliferation of NPC
      cells treated with triptolide in a dose- and time-dependent ways. Effects of
      triptolide on NPC cell cycle and apoptosis were investigated by flow cytometric
      analysis. EBNA1 expression in mRNA and protein levels was determined by
      quantitative real-time PCR and Western blot, respectively. RESULTS: Our results
      showed that triptolide effectively inhibited proliferation of NPC cells.
      Triptolide arrested NPC cell cycles in S phase and induced apoptosis through a
      caspase-9-dependent apoptosis pathway. Low-dose of triptolide reduced the half
      life of EBNA1 and significantly decreased EBNA1 expression by promoting the
      process of proteasome-ubiquitin pathway. Over-expression of EBNA1, which was
      independent from EBV genome, effectively attenuated the apoptosis induced by
      triptolide. In addition, triptolide significantly inhibited proliferations of
      tumors induced by EBV-positive cells in vivo. Furthermore, EBNA1 were expressed
      in all NPC biopsies of Chinese patients. CONCLUSIONS: In summary, our study
      provides the evidence that triptolide induces EBNA1 degradation and stimulates
      NPC apoptosis through mitochondria apoptotic pathway. In addition, EBNA1 assists
      NPC cells to resist triptolide-induced apoptosis through inhibiting caspase-9
      dependent apoptotic pathway.

PMID- 30111355
TI  - CSF H3F3A K27M circulating tumor DNA copy number quantifies tumor growth and in
      vitro treatment response.

PMID- 30111356
TI  - Cerebrospinal fluid soluble TREM2 levels in frontotemporal dementia differ by
      genetic and pathological subgroup.
AB  - BACKGROUND: Reliable biomarkers of frontotemporal dementia (FTD) are currently
      lacking. FTD may be associated with chronic immune dysfunction, microglial
      activation and raised inflammatory markers, particularly in progranulin (GRN)
      mutation carriers. Levels of soluble triggering receptor expressed on myeloid
      cells 2 (sTREM2) are elevated in Alzheimer's disease (AD), but they have not been
      fully explored in FTD. METHODS: We investigated whether cerebrospinal fluid (CSF)
      sTREM2 levels differ between FTD and controls, across different clinical and
      genetic subtypes of FTD, or between individuals with FTD due to AD versus non-AD
      pathology (based on CSF neurodegenerative biomarkers). We also assessed
      relationships between CSF sTREM2 and other CSF biomarkers (total tau [T-tau], tau
      phosphorylated at position threonine-181 [P-tau] and beta-amyloid 1-42 [Abeta42])
      and age and disease duration. Biomarker levels were measured using immunoassays
      in 17 healthy controls and 64 patients with FTD (behavioural variant FTD, n = 20;
      primary progressive aphasia, n = 44). Ten of 64 had familial FTD, with mutations
      in GRN (n = 3), MAPT (n = 4), or C9orf72 (n = 3). Fifteen of 64 had
      neurodegenerative biomarkers consistent with AD pathology (11 of whom had
      logopenic variant PPA). Levels were compared using multivariable linear
      regressions. RESULTS: CSF sTREM2 levels did not differ between FTD and controls
      or between clinical subgroups. However, GRN mutation carriers had higher levels
      than controls (mean ([SD] = 9.7 [2.9] vs. 6.8 [1.6] ng/ml; P = 0.028) and MAPT
      (3.9 [1.5] ng/ml; P = 0.003] or C9orf72 [4.6 [1.8] ng/ml; P = 0.006) mutation
      carriers. Individuals with AD-like CSF had higher sTREM2 levels than those with
      non-AD-like CSF (9.0 [3.6] vs. 6.9 [3.0] ng/ml; P = 0.029). CSF sTREM2 levels
      were associated with T-tau levels in control and FTD groups and also with P-tau
      in those with FTD and AD-like CSF. CSF sTREM2 levels were influenced by both age
      and disease duration in FTD. CONCLUSIONS: Although CSF sTREM2 levels are not
      raised in FTD overall or in a particular clinical subtype of FTD, levels are
      raised in familial FTD associated with GRN mutations and in FTD syndromes due to
      AD pathology. Because CSF sTREM2 levels correlate with a marker of neuronal
      injury (T-tau), sTREM2 should be explored as a biomarker of disease intensity in
      future longitudinal studies of FTD.

PMID- 30111357
TI  - A comparative clinical study of PF-06410293, a candidate adalimumab biosimilar,
      and adalimumab reference product (Humira(r)) in the treatment of active
      rheumatoid arthritis.
AB  - BACKGROUND: This double-blind, randomized, 78-week study evaluated the efficacy,
      safety, immunogenicity, pharmacokinetics, and pharmacodynamics of PF-06410293, a
      candidate adalimumab biosimilar, versus adalimumab reference product (Humira(r))
      sourced from the EU (adalimumab-EU) in biologic-naive patients with active
      rheumatoid arthritis (RA) despite methotrexate (MTX) (10-25 mg/week). We report
      results for the first 26 weeks of treatment. METHODS: Patients with active RA (N
      = 597) were randomly assigned (1:1) to PF-06410293 or adalimumab-EU, while
      continuing with MTX treatment. The primary endpoint was American College of
      Rheumatology 20% improvement (ACR20) at week 12. Therapeutic equivalence was
      concluded if the two-sided 95% confidence interval (CI) for the ACR20 difference
      between the two arms was entirely contained within the symmetric equivalence
      margin (+/-14%). Additionally, a two-sided 90% CI was calculated by using an
      asymmetric equivalence margin (-12%, 15%). Secondary efficacy endpoints to week
      26 included ACR20/50/70, change from baseline Disease Activity Score based on
      high-sensitivity C-reactive protein [DAS28-4(CRP)], European League Against
      Rheumatism (EULAR) response, DAS28-4(CRP) of less than 2.6, and ACR/EULAR
      remission. QuantiFERON-TB testing was performed at screening and week 26.
      RESULTS: Patients (78.7% of whom were female and whose mean age was 52.5 years)
      had a mean baseline RA duration of 6.8 years. The mean baseline DAS28-4(CRP)
      values were 5.9 (PF-06410293) and 6.1 (adalimumab-EU). The observed week-12 ACR20
      values were 68.7% (PF-06410293) and 72.7% (adalimumab-EU) in the intention-to
      treat population. With non-responder imputation, the treatment difference in week
      12 ACR20 was -2.98% and corresponding CIs-95% CI (-10.38%, 4.44%) and 90% CI (
      9.25%, 3.28%)-were entirely contained within the equivalence margins (symmetric
      and asymmetric, respectively). The secondary efficacy endpoints were similar
      between arms. Over 26 weeks, injection-site reactions occurred in 1.7% versus
      2.0%, hypersensitivity events in 4.4% versus 8.4%, pneumonia in 0.7% versus 2.0%,
      and opportunistic infections in 2.4% versus 1.7% in the PF-06410293 and
      adalimumab-EU arms, respectively. One death due to myocardial infarction occurred
      (adalimumab-EU arm). Rates of anti-drug antibody incidence were 44.4% (PF
      06410293) and 50.5% (adalimumab-EU). CONCLUSIONS: The study results demonstrate
      that efficacy, safety, and immunogenicity of PF-06410293 and adalimumab-EU were
      similar during the first 26 weeks of treatment in patients with active RA on
      background MTX. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02480153 .
      First posted on June 24, 2015; EU Clinical Trials Register EudraCT number: 2014
      000352-29 . Start date: October 27, 2014.

PMID- 30111358
TI  - The relationship between ferritin and urate levels and risk of gout.
AB  - BACKGROUND: Ferritin positively associates with serum urate and an interventional
      study suggests that iron has a role in triggering gout flares. The objective of
      this study was to further explore the relationship between iron/ferritin and
      urate/gout. METHODS: European (100 cases, 60 controls) and Polynesian (100 cases,
      60 controls) New Zealand (NZ) males and 189 US male cases and 60 male controls
      participated. The 10,727 participants without gout were from the Jackson Heart
      (JHS; African American = 1260) and NHANES III (European = 5112; African American
      = 4355) studies. Regression analyses were adjusted for age, sex, body mass index
      and C-reactive protein. To test for a causal relationship between ferritin and
      urate, bidirectional two-sample Mendelian randomization analysis was performed.
      RESULTS: Serum ferritin positively associated with gout in NZ Polynesian (OR (per
      10 ng ml- 1 increase) = 1.03, p = 1.8E-03) and US (OR = 1.11, p = 7.4E-06) data
      sets but not in NZ European (OR = 1.00, p = 0.84) data sets. Ferritin positively
      associated with urate in NZ Polynesian (beta (mg dl- 1) = 0.014, p = 2.5E-04),
      JHS (beta = 0.009, p = 3.2E-05) and NHANES III (European beta = 0.007, p = 5.1E
      11; African American beta = 0.011, p = 2.1E-16) data sets but not in NZ European
      (beta = 0.009, p = 0.31) or US (beta = 0.041, p = 0.15) gout data sets. Ferritin
      positively associated with the frequency of gout flares in two of the gout data
      sets. By Mendelian randomization analysis a one standard deviation unit increase
      in iron and ferritin was, respectively, associated with 0.11 (p = 8E-04) and 0.19
      mg dl- 1 (p = 2E-04) increases in serum urate. There was no evidence for a causal
      effect of urate on iron/ferritin. CONCLUSIONS: These data replicate the
      association of ferritin with serum urate. Increased ferritin levels associated
      with gout and flare frequency. There was evidence of a causal effect of iron and
      ferritin on urate.

PMID- 30111360
TI  - Unhealthy weight among children in Spain and the role of the home environment.
AB  - OBJECTIVE: Unhealthy weight is a major global health concern. This study examines
      unhealthy weight among children in Spain and the role of the home environment
      therein. Data are from a 2010 national survey of families with children. We
      examined unhealthy weight among children ages 5-10 years using the WHO Child
      Growth Standards and used multivariate logistic regression to assess associations
      with family characteristics. RESULTS: There was a high prevalence of unhealthy
      weight, with only 46% of children at normal weight. Both underweight and obesity
      were higher among boys (14%; 22%) than girls (13%; 12%). Underweight and obesity
      were higher among children of mothers with obesity and those with unemployed
      parents. Obesity was higher among children of mothers who were less educated
      (35%) and among children of immigrants (19%). We find high levels of unhealthy
      weight in children, with both underweight and obesity being predicted by the same
      family environment characteristics.

PMID- 30111361
TI  - Adjuvant chemotherapy does not benefit patients with esophageal squamous cell
      carcinoma treated with definitive chemoradiotherapy.
AB  - BACKGROUND: The aim of the present study was to assess the efficacy of adjuvant
      chemotherapy (AC) in patients with esophageal squamous cell carcinoma (ESCC)
      treated with definitive chemoradiotherapy (CRT). METHODS: The clinical data of
      patients with ESCC treated with chemoradiotherapy with or without AC were
      collected and retrospectively reviewed. The overall survival (OS), locoregional
      failure-free survival (LFFS) and distant failure-free survival (DFFS) rates were
      analyzed statistically. RESULTS: A total of 187 patients fulfilled the inclusion
      criteria, 98 of whom were treated with CRT-alone, while 89 were treated with CRT
      AC. Patient characteristics did not significantly differ between the CRT-alone
      and CRT-AC groups, with the exception of sex and the number of cycles of
      concurrent chemotherapy. Following CRT, 50 patients achieved complete response
      (CR), 67 had partial response (PR), 63 patients maintained stable disease (SD)
      and 7 developed progression of disease (PD). The OS, LFFS and DFFS at 1, 2 and 5
      years for the entire cohort were 67.5, 41.4 and 27.2%; 68.7, 57.9 and 52.4%; and
      78.5, 68.9 and 63.9%, respectively. The clinical N-stage, M-stage, and short-term
      response to CRT were identified as significant factors that influenced patient
      prognosis. No significant differences in OS, LFFS or DFFS were observed between
      the CRT-alone and CRT-AC groups for the entire cohort and for clinical N-stage,
      clinical M-stage and short-term response subgroups. CONCLUSIONS: The short-term
      response to CRT and the tumor clinical stage were significant prognosis factors
      for patients with ESCC treated with CRT. With current chemotherapy regimens, AC
      did not improve survival for patients with ESCC treated with CRT. The
      retrospective nature of the current study serves as a limitation; thus, further
      clinical trials are required to evaluate the efficacy of AC in patients with ESCC
      treated with CRT.

PMID- 30111363
TI  - Evidence-based guidelines for physiotherapy management of patients with multiple
      myeloma: study protocol.
AB  - BACKGROUND: Patients with multiple myeloma (MM) are often treated with
      chemotherapy, radiation, and, if indicated, autologous stem cell transplant. In
      addition to side effects of the treatment, patients with MM often have bone pain,
      pathological fractures, spinal cord compressions, fatigue, and muscle weakness,
      which negatively impact functional performance and quality of life. Currently,
      there are no related guidelines for safe and effective physiotherapy (PT)
      management. Accordingly, the aim of the present study is to develop guidelines
      for effective physiotherapy management of patients with MM by systematically
      reviewing and evaluating the available evidence followed by a consensus process
      to specifically describe the research questions as detailed below.
      METHODS/DESIGN: Physiotherapy management guidelines for patients with multiple
      myeloma will be developed based on the results of a systematic search of the
      following databases: US National Library of Medicine Database (PubMed), Medical
      Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica
      Database (EMBASE), Cumulative Index to Nursing and Allied Health Literature
      (CINAHL), Elton B. Stephens Co. (EBSCO), Web of Science, Database of Abstracts of
      Reviews of Effects (DARE), Cochrane Database of Systematic Review, and
      Physiotherapy Evidence Database (PEDro). All articles will be screened for
      inclusion and exclusion criteria. Relevant potential articles will be identified
      and systematically reviewed for final phase of inclusion. Two independent
      reviewers will systematically review and analyze the quality of identified
      articles using standardized assessment tools. Scientific conclusions will be
      drawn and recommendations will be made based on a critical appraisal process. The
      guideline development will also be based on the team's judgment about the overall
      quality of the studies and a consensus process. DISCUSSION: Draft guidelines will
      be developed in the form of action statements based on the strength of evidence
      and grades of recommendations. The draft guidelines will be reviewed internally
      by two independent reviewers using AGREE II and externally by a methodological
      expert from Evidence-Based Care - Cancer Care Ontario and will be sent to the
      Canadian Physiotherapy Association (CPA) for feedback from physiotherapists.
      SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017064056.

PMID- 30111359
TI  - Evolutionarily conserved partial gene duplication in the Triticeae tribe of
      grasses confers pathogen resistance.
AB  - BACKGROUND: The large and highly repetitive genomes of the cultivated species
      Hordeum vulgare (barley), Triticum aestivum (wheat), and Secale cereale (rye)
      belonging to the Triticeae tribe of grasses appear to be particularly rich in
      gene-like sequences including partial duplicates. Most of them have been
      classified as putative pseudogenes. In this study we employ transient and stable
      gene silencing- and over-expression systems in barley to study the function of
      HvARM1 (for H. vulgare Armadillo 1), a partial gene duplicate of the U
      box/armadillo-repeat E3 ligase HvPUB15 (for H. vulgare Plant U-Box 15). RESULTS:
      The partial ARM1 gene is derived from a gene-duplication event in a common
      ancestor of the Triticeae and contributes to quantitative host as well as nonhost
      resistance to the biotrophic powdery mildew fungus Blumeria graminis. In barley,
      allelic variants of HvARM1 but not of HvPUB15 are significantly associated with
      levels of powdery mildew infection. Both HvPUB15 and HvARM1 proteins interact in
      yeast and plant cells with the susceptibility-related, plastid-localized barley
      homologs of THF1 (for Thylakoid formation 1) and of ClpS1 (for Clp-protease
      adaptor S1) of Arabidopsis thaliana. A genome-wide scan for partial gene
      duplicates reveals further events in barley resulting in stress-regulated,
      potentially neo-functionalized, genes. CONCLUSION: The results suggest neo
      functionalization of the partial gene copy HvARM1 increases resistance against
      powdery mildew infection. It further links plastid function with susceptibility
      to biotrophic pathogen attack. These findings shed new light on a novel mechanism
      to employ partial duplication of protein-protein interaction domains to
      facilitate the expansion of immune signaling networks.

PMID- 30111362
TI  - Missense mutation in SLIT2 associated with congenital myopia, anisometropia,
      connective tissue abnormalities, and obesity.
AB  - BACKGROUND: SLIT2 is a protein ligand for the Roundabout (ROBO) receptor and was
      found to play a major role in repulsive midline axon guidance in central nervous
      system development. Based on studies utilizing knockout models, it has been
      postulated that SLIT2 is important for preventing inappropriate axonal routing
      during mammalian optic chiasm development. METHODS: Case report. RESULTS: Here,
      we report a case of congenital myopia, anisometropia, and obesity in a patient
      with a SLIT2 point mutation. Examination of the patient's skin biopsy revealed
      abnormalities in elastin and collagen fibrils that suggest an underlying
      connective tissue disorder. Structural modeling placed the novel mutation
      (p.D1407G) in the EGF-like domain 8 and was predicted to affect interactions with
      SLIT2 binding partners. CONCLUSIONS: To the authors' knowledge, this is the first
      report of a SLIT2 variant in the context of these ocular findings.

PMID- 30111364
TI  - Safer tattooing interventions in prisons: a systematic review and call to action.
AB  - BACKGROUND: Worldwide more than ten million people are detained at any given
      time. Between 5 and 60% of people experiencing incarceration report receipt of a
      tattoo in prison - mostly clandestine, which is associated with risks of blood
      borne infections (BBIs). Although safer tattooing techniques are effective in
      preventing BBI transmission and available to the general population, there is
      limited knowledge about the impact of safer tattooing strategies in prisons in
      terms of health outcomes, changes in knowledge and behaviors, and best practice
      models for implementation. The objective of this research was to identify and
      review safer tattooing interventions. METHODS: We conducted a systematic review
      of the literature. Studies of all design types were included if they were
      published until 27 June 2018, the population was incarcerated adults, they
      reported quantitative outcomes, and were published in English, French, or
      Spanish. RESULTS: Of 55 papers retrieved from the initial search, no peer
      reviewed article was identified. One paper from the grey literature described a
      multi-site pilot project in Canada. Its evaluation suggested that the project was
      effective in enhancing knowledge of incarcerated people and prison staff on
      standard precautions, had the potential to reduce harm, provided vocational
      opportunities, and was feasible although enhancements were needed to improve
      implementation issues and efficiency. CONCLUSIONS: Although access to preventive
      services, including to safer tattooing interventions, is a human right and
      recommended by United Nations agencies as part of a comprehensive package of harm
      reduction interventions in prisons, this review identified only a few promising
      strategies for safer tattooing interventions in carceral settings. We call upon
      governments, criminal justice authorities, non-governmental organizations, and
      academic institutions to implement safer tattooing projects that adhere to the
      following guiding principles: i) integration of methodologically-rigorous
      implementation research; ii) involvement of key stakeholders (incarcerated
      people, prison authorities, research partners) in the project design,
      implementation, and research; iii) integration into a comprehensive package of
      BBI prevention, treatment, and care, using a stepwise approach that considers
      local resources and acceptability; and iv) publication and dissemination of
      findings, and scaling up efforts. PROSPERO REGISTRATION: CRD42017072502 .

PMID- 30111365
TI  - The multivariate physical activity signature associated with metabolic health in
      children.
AB  - BACKGROUND: Physical activity is a cornerstone for promoting good metabolic
      health in children, but it is heavily debated which intensities (including
      sedentary time) are most influential. A fundamental limitation to current
      evidence for this relationship is the reliance on analytic approaches that cannot
      handle collinear variables. The aim of the present study was to determine the
      physical activity signature related to metabolic health in children, by
      investigating the association pattern for the whole spectrum of physical activity
      intensities using multivariate pattern analysis. METHODS: We used a sample of 841
      children (age 10.2 +/- 0.3 years; BMI 18.0 +/- 3.0; 50% boys) from the Active
      Smarter Kids study, who provided valid data on accelerometry (ActiGraph GT3X+)
      and several indices of metabolic health (aerobic fitness, abdominal fatness,
      insulin sensitivity, lipid metabolism, blood pressure) that were used to create a
      composite metabolic health score. We created 16 physical activity variables
      covering the whole intensity spectrum (from 0-100 to >= 8000 counts per minute)
      and used multivariate pattern analysis to analyze the data. RESULTS: Physical
      activity intensities in the vigorous range (5000-7000 counts per minute) were
      most strongly associated with metabolic health. Moderate intensity physical
      activity was weakly related to health, and sedentary time and light physical
      activity were not related to health. CONCLUSIONS: This study is the first to
      determine the multivariate physical activity signature related to metabolic
      health in children across the whole intensity spectrum. This novel approach shows
      that vigorous physical activity is strongest related to metabolic health. We
      recommend future studies adapt a multivariate analytic approach to further
      develop the field of physical activity epidemiology. TRIAL REGISTRATION: The
      study was registered in Clinicaltrials.gov (www.clinicaltrials.gov) 7th of April
      2014 with identification number NCT02132494 .

PMID- 30111367
TI  - A quadricuspid aortic valve in an asymptomatic 40-year-old man: a case report.
AB  - BACKGROUND: Integrated transthoracic and transesophageal echocardiography enables
      identification and characterization of a quadricuspid aortic valve anomaly. CASE
      PRESENTATION: A totally asymptomatic 40-year-old white man was referred to our
      Division of Cardiology after accidental finding of a heart murmur.
      Transesophageal echocardiography detected a quadricuspid aortic valve
      characterized by four cusps of equal size and severe aortic valvular
      regurgitation, without any further anomalies. He underwent a successful aortic
      valve repair. CONCLUSIONS: Quadricuspid aortic valve anomaly is a rare congenital
      cardiac defect that can cause progressive valvular complications.

PMID- 30111366
TI  - Systems level expression correlation of Ras GTPase regulators.
AB  - BACKGROUND: Proteins of the ubiquitously expressed core proteome are
      quantitatively correlated across multiple eukaryotic species. In addition, it was
      found that many protein paralogues exhibit expression anticorrelation, suggesting
      that the total level of protein with a given functionality must be kept constant.
      METHODS: We performed Spearman's rank correlation analyses of gene expression
      levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins
      across tissues and across individuals for each tissue. A large set of published
      data for normal tissues from a wide range of species, human cancer tissues and
      human cell lines was analysed. RESULTS: We show that although the multidomain
      regulatory proteins of Ras GTPases exhibit considerable tissue and individual
      gene expression variability, their total amounts are balanced in normal tissues.
      In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains
      of Ras GTPases can vary considerably, but each person has balanced GEF and GAP
      levels. This balance is impaired in cell lines and in cancer tissues for some
      individuals. CONCLUSIONS: Our results are relevant for critical considerations of
      knock out experiments, where functionally related homologs may compensate for the
      down regulation of a protein.

PMID- 30111369
TI  - Biomedical ontology alignment: an approach based on representation learning.
AB  - BACKGROUND: While representation learning techniques have shown great promise in
      application to a number of different NLP tasks, they have had little impact on
      the problem of ontology matching. Unlike past work that has focused on feature
      engineering, we present a novel representation learning approach that is tailored
      to the ontology matching task. Our approach is based on embedding ontological
      terms in a high-dimensional Euclidean space. This embedding is derived on the
      basis of a novel phrase retrofitting strategy through which semantic similarity
      information becomes inscribed onto fields of pre-trained word vectors. The
      resulting framework also incorporates a novel outlier detection mechanism based
      on a denoising autoencoder that is shown to improve performance. RESULTS: An
      ontology matching system derived using the proposed framework achieved an F-score
      of 94% on an alignment scenario involving the Adult Mouse Anatomical Dictionary
      and the Foundational Model of Anatomy ontology (FMA) as targets. This compares
      favorably with the best performing systems on the Ontology Alignment Evaluation
      Initiative anatomy challenge. We performed additional experiments on aligning FMA
      to NCI Thesaurus and to SNOMED CT based on a reference alignment extracted from
      the UMLS Metathesaurus. Our system obtained overall F-scores of 93.2% and 89.2%
      for these experiments, thus achieving state-of-the-art results. CONCLUSIONS: Our
      proposed representation learning approach leverages terminological embeddings to
      capture semantic similarity. Our results provide evidence that the approach
      produces embeddings that are especially well tailored to the ontology matching
      task, demonstrating a novel pathway for the problem.

PMID- 30111368
TI  - Guidelines for training in cardiovascular magnetic resonance (CMR).
AB  - These "Guidelines for training in Cardiovascular Magnetic Resonance" were
      developed by the Certification Committee of the Society for Cardiovascular
      Magnetic Resonance (SCMR) and approved by the SCMR Board of Trustees.

PMID- 30111370
TI  - Pay for performance program reduces treatment needed diabetic retinopathy - a
      nationwide matched cohort study in Taiwan.
AB  - BACKGROUND: Pay-for-Performance programs have shown improvement in indicators
      monitoring adequacy and target achievement in diabetic care. However, less is
      known regarding the impact of this program on the occurrence and long-term
      effects of diabetic retinopathy. The objective of this study was to determine the
      effect of pay-for-performance program on the development of treatment needed for
      diabetic retinopathy in type 2 diabetes patients. METHODS: We conducted a
      nationwide retrospective cohort study with a matching design using the Taiwan
      National Health Insurance Research Database from 2000 to 2012. The outcome was
      defined as the treatment needed diabetic retinopathy. We matched Pay-for
      Performance and non-Pay-for-Performance groups for age, gender, year diabetes was
      diagnosed and study enrollment, and duration of follow-up. RESULTS: A total of
      9311 patients entered the study cohort, of whom 2157 were registered in the Pay
      for-Performance group and 7154 matched in the non-Pay-for-Performance group. The
      incidence of treatment needed diabetic retinopathy was not significantly
      different in two groups. However, the incidence of treatment needed diabetic
      retinopathy was significantly different if restricted the non-Pay-for-Performance
      group who had at least 1 eye examination or optical coherence tomography within 1
      year (adjusted hazard ratio, 0.78; 95% confidence interval, 0.64-0.94).
      CONCLUSIONS: Pay-for-Performance is valuable in preventing the development of
      treatment needed diabetic retinopathy, which could be attributed to the routine
      eye examination required in the Pay-for-Performance program. We could improve our
      diabetic care by promoting eye health education and patient awareness on the
      importance of regular examinations.

PMID- 30111371
TI  - Loneliness among mothers raising children under the age of 3 years and predictors
      with special reference to the use of SNS: a community-based cross-sectional
      study.
AB  - BACKGROUND: Loneliness in mothers raising children can adversely impact the
      health of their children and lead to child abuse, depression, and deterioration
      of mothers' health. Few studies to date have specifically assessed the
      association between loneliness and social factors, including the use of social
      network sites (SNSs), and personal factors. This study aimed to identify
      predictors of loneliness in mothers raising children, with special reference to
      SNS use. METHODS: This cross-sectional study involved an anonymous self-reported
      questionnaire survey of mothers participating in the health check-ups for their
      children in Nagahama City, Japan, from July 28 to September 29, 2014. The
      following items were assessed: revised UCLA Loneliness Scale, "Secure" subscale
      of the Internal Working Model Scale (IWMS-S), psychological distress scale (K6),
      abbreviated Lubben Social Network Scale (LSNS-6), and types of communication
      devices and information sources. Multiple regression analysis was performed using
      the Loneliness Scale score as the dependent variable. RESULTS: Among 763 mothers
      attending health check-ups for children in Nagahama City, 715 were available for
      the survey. Among a total of 638 respondents, data from 523 mothers were analyzed
      (valid response rate: 73.1%). The mean Loneliness Scale score +/- standard
      deviation was 36.1 +/- 9.7. The multiple regression analysis revealed that
      loneliness was significantly associated with being financially worse-off (beta = 
      3.35, p = 0.004) and struggling (beta = - 2.47, p = 0.047); having a smaller
      family social network (beta = - 0.32, p = 0.032), having fewer friends (beta = -
      0.49, p = 0.001), and having a smaller SNS network (beta = - 0.21, p = 0.018); a
      lower secure subscale score on the IWMS-S (beta = - 0.56, p < 0.001); and a K6
      score of >=5 (beta = 4.24, p < 0.001). CONCLUSION: The degree of loneliness in
      mothers raising children was associated with a smaller social network, lower
      secure attachment style, and a higher possibility of psychological distress.
      These factors should be considered when developing effective interventions
      against loneliness in mothers raising children.

PMID- 30111372
TI  - (Update of a) systematic review on the impact of elective early term (< 39th
      gestational week) caesarean sections on maternal and neonatal health - a
      protocol.
AB  - BACKGROUND: The rate of caesarean sections increased in the last decades to about
      30% of births in western populations. Many caesarean sections are electively
      planned without an urgent medical reason for mother or child. Especially in women
      with a foregoing caesarean section, the procedure is planned early. An early
      caesarean section though may harm the newborn. Our aim is to evaluate the
      gestational time point after the 37th gestational week (after prematurity = term)
      of performing an elective caesarean section with the lowest morbidity for mother
      and child. METHODS: This is an update of a systematic review previously carried
      out on behalf of the German Federal Ministry of Health. We will perform a
      systematic literature search in MEDLINE, EMBASE, CENTRAL and CINAHL. Our primary
      outcome is the rate of admissions to the neonatal intensive care unit in early
      versus late term neonates. We will include (quasi) randomized controlled trials
      and cohort studies. The studies should include pregnant women who have an
      elective caesarean section at term. We will screen titles and abstracts and the
      identified full texts of studies for eligibility. Risk of bias will be assessed
      with the Cochrane Risk of Bias Tool for Randomized Trials or with the Risk of
      Bias Tool for Non-Randomized Studies of Interventions (ROBINS-I). These tasks
      will be performed independently by two reviewers. Data will be extracted in
      beforehand piloted extraction tables. A dose-response meta-analysis will be
      performed. DISCUSSION: Our aim is to reach a higher validity in the assessment of
      the time point of elective caesarean sections by performing a meta-analysis to
      support recommendations for clinical practice. We assume to identify less
      randomized controlled trials but a large number of cohort studies analyzing the
      given question. We will discuss similarities and differences in included studies
      as well as methodological strengths and weaknesses. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42017078231.

PMID- 30111374
TI  - Bundle of care taking into account time to improve long-term outcome after
      cardiac arrest.

PMID- 30111373
TI  - TNFAIP3 is required for FGFR1 activation-promoted proliferation and tumorigenesis
      of premalignant DCIS.COM human mammary epithelial cells.
AB  - BACKGROUND: Although ductal carcinoma in situ (DCIS) is a non-invasive breast
      cancer, many DCIS lesions may progress to invasive cancer and the genes and
      pathways responsible for its progression are largely unknown. FGFR1 plays an
      important role in cell proliferation, differentiation and carcinogenesis. The
      purpose of this study is to examine the roles of FGFR1 signaling in gene
      expression, cell proliferation, tumor growth and progression in a non-invasive
      DCIS model. METHODS: DCIS.COM cells were transfected with an empty vector to
      generate DCIS-Ctrl cells. DCIS-iFGFR1 cells were transfected with an AP20187
      inducible iFGFR1 vector to generate DCIS-iFGFR1 cells. iFGFR1 consists of the v
      Src myristoylation membrane-targeting sequence, FGFR1 cytoplasmic domain and the
      AP20187-inducible FKBP12 dimerization domain, which simulates FGFR1 signaling.
      The CRISPR/Cas9 system was employed to knockout ERK1, ERK2 or TNFAIP3 in DCIS
      iFGFR1 cells. Established cell lines were treated with/without AP20187 and
      with/without FGFR1, MEK, or ERK1/2 inhibitor. The effects of these treatments
      were determined by Western blot, RNA-Seq, real-time RT-PCR, cell proliferation,
      mammosphere growth, xenograft tumor growth, and tumor histopathological assays.
      RESULTS: Activation of iFGFR1 signaling in DCIS-iFGFR1 cells enhanced ERK1/2
      activities, induced partial epithelial-to-mesenchymal transition (EMT) and
      increased cell proliferation. Activation of iFGFR1 signaling promoted DCIS growth
      and progression to invasive cancer derived from DCIS-iFGFR1 cells in mice.
      Activation of iFGFR1 signaling also altered expression levels of 946 genes
      involved in cell proliferation, migration, cancer pathways, and other molecular
      and cellular functions. TNFAIP3, a ubiquitin-editing enzyme, is upregulated by
      iFGFR1 signaling in a FGFR1 kinase activity and in an ERK2-dependent manner.
      Importantly, TNFAIP3 knockout not only inhibited the AP20187-induced
      proliferation and tumor growth of DCIS-iFGFR1 cells, but also further reduced
      baseline proliferation and tumor growth of DCIS-iFGFR1 cells without AP20187
      treatment. CONCLUSIONS: Activation of iFGFR1 promotes ERK1/2 activity, EMT, cell
      proliferation, tumor growth, DCIS progression to invasive cancer, and altered the
      gene expression profile of DCIS-iFGFR1 cells. Activation of iFGFR1 upregulated
      TNFAIP3 in an ERK2-dependent manner and TNFAIP3 is required for iFGFR1 activation
      promoted DCIS.COM cell proliferation, mammosphere growth, tumor growth and
      progression. These results suggest that TNFAIP3 may be a potential target for
      inhibiting DCIS growth and progression promoted by FGFR1 signaling.

PMID- 30111375
TI  - Mink (Neovison vison) kits with pre-weaning diarrhea have elevated serum amyloid
      A levels and intestinal pathomorphological similarities with New Neonatal Porcine
      Diarrhea Syndrome.
AB  - BACKGROUND: Pre-weaning diarrhea (PWD) is a syndrome affecting farm-raised
      neonatal mink kits. Apart from diarrhea it causes greasy skin exudation,
      dehydration, and distressed behavior and can ultimately lead to death. No
      specific causative agents have been identified and the syndrome is regarded as
      multifactorial. The aim of the present study was to investigate a possible
      inflammatory state in mink kits with PWD, as indicated by raised serum
      concentrations of the acute phase protein serum amyloid A (SAA) and by changes in
      intestinal pathomorphology and intestinal contents of bacteria. Samples collected
      from 20 diarrheic mink kits with PWD and 20 age-matched non-diarrheic control
      mink kits from two commercial Danish farms during the pre-weaning period (April
      May) in 2016 were analyzed. RESULTS: Concentrations of SAA in serum samples from
      mink kits with PWD were significantly higher (up to 1000-fold) compared to non
      diarrheic control mink kits. Significant features of enterocytic vacuolization,
      atrophy and fusion of villi in jejunum and mucosal atrophy of the colon of kits
      with PWD were found. Moreover, attachment of coccoid bacteria to enterocytes was
      more often found in kits suffering from PWD, while intra-cytoplasmic eosinophil
      bodies were more frequently observed in control kits. Cellular infiltrations with
      mononuclear and neutrophil leukocytes were not associated with disease status.
      Bacteria from the Staphylococcus intermedius group, such as Staphylococcus
      delphini, were more frequently cultivated from control mink kits, whereas
      Enterococcus spp. dominated in mink kits with PWD. Escherichia coli was
      cultivated from both control and mink kits with PWD, but with a higher frequency
      from mink kits with PWD. CONCLUSION: A significant increase in circulating
      concentrations of SAA was found in PWD affected mink kits from 6 to 23 days old
      compared to controls. The histopathological changes in PWD mink kits suggest that
      the type of diarrhea is secretory. Attachment of coccoid bacteria, therefore,
      might be responsible for an enterotoxic effect causing a loss of balance in
      movements of ions and water leading to the vacuolization and swelling of the
      enterocytes. The slight to moderate infiltrations of neutrophils irrespectively
      of diarrheic status and the attachment of coccoid bacteria to enterocytes are
      comparable to observations found in piglets suffering from New Neonatal Porcine
      Diarrhea Syndrome. Mechanisms behind the correlation between increased SAA levels
      and the observed pathological intestinal features remain obscure.

PMID- 30111376
TI  - Per-organ assessment of subject-induced susceptibility distortion for MR-only
      male pelvis treatment planning.
AB  - BACKGROUND: Patient-specific distortions, particularly near tissue/air
      interfaces, require assessment for magnetic resonance (MR) only radiation
      treatment planning (RTP). However, patients are dynamic due to changes in
      physiological status during imaging sessions. This work investigated changes in
      subject-induced susceptibility distortions to pelvic organs at different bladder
      states to support pelvis MR-only RTP. METHODS: Pelvises of 9 healthy male
      volunteers were imaged at 1.0 Tesla (T), 1.5 T, and 3.0 T. Subject-induced
      susceptibility distortion field maps were generated using a dual-echo gradient
      recalled echo (GRE) sequence with B0 field maps obtained from the phase
      difference between the two echoes acquired at several bladder volume states (3
      4/subject, 32 overall). T2 turbo spin echo images were also acquired at each
      bladder state for organ delineation. Magnet central frequency was tracked over
      time. Distortion map differences and boxplots were computed to characterize
      changes within the clinical target volume (CTV), bladder, seminal vesicles, and
      prostate volumes. RESULTS: The time between the initial and final B0 maps was
      42.6 +/- 13.9 (range: 13.2-62.1) minutes with minimal change in magnet central
      frequency (0.02 +/- 0.05 mm (range: - 0.06 - 0.12 mm)). Subject-induced
      susceptibility distortion across all bladder states, field strengths, and
      subjects was relatively small (1.4-1.9% of all voxels in the prostate and seminal
      vesicles were distorted > 0.5 mm). In the bladder, no voxels exhibited
      distortions > 1 mm. An extreme case acquired at 3.0 T with a large volume of
      rectal air yielded 27.4-34.6% of voxels within the CTVs had susceptibility
      induced distortions > 0.5 mm across all time points. CONCLUSIONS: Our work
      suggests that subject-induced susceptibility distortions caused by bladder/rectal
      conditions are generally small and subject-dependent. Local changes may be non
      negligible within the CTV, thus proper management of filling status is warranted.
      Future work evaluating the impact of multiple models to accommodate for extreme
      status changes may be advantageous.

PMID- 30111377
TI  - Detection of GNAS mutations in intramuscular / cellular myxomas as diagnostic
      tool in the classification of myxoid soft tissue tumors.
AB  - BACKGROUND: Intramuscular / cellular myxomas and low-grade myxofibrosarcomas are
      two different tumor entities with a significant histological overlap, especially
      if dealing with small biopsies. Despite the morphological similarities, they
      differ considerably in their biological behaviour. Intramuscular / cellular
      myxoma rarely shows signs of recurrence and never metastasizes, in contrast to
      myxofibrosarcoma that tends to recur more aggressively and to metastasize
      haematologically. Therefore, it is of great importance to distinguish these
      lesions - evaluation of GNAS mutation status could be of tremendous help.
      METHODS: We reviewed 13 cases with intramuscular / cellular myxomas. The 13 cases
      included 5 men and 8 women, aged from 33 to 71 years (mean age 55.5 years).
      Immunohistochemistry was performed as well as next generation sequencing. Ten
      cases were located in the lower extremities and three cases were located in the
      upper extremities. Two lesions were initially misdiagnosed as a low-grade
      myxofibrosarcoma. RESULTS: Performing next generation sequencing 12 out of 13
      specimens showed a GNAS mutation. CONCLUSIONS: Our findings demonstrate that GNAS
      mutations are more common in intramuscular / cellular myxomas, than had been
      reported in literature in the past. Next generation sequencing for determining
      GNAS mutation status on small biopsies or diagnostically challenging cases
      facilitates the diagnosis of intramuscular / cellular myxoma and separates this
      tumor entity from its mimics.

PMID- 30111378
TI  - Prevention of seroma following inguinal lymph node dissection with prophylactic,
      incisional, negative-pressure wound therapy (SEROMA trial): study protocol for a
      randomized controlled trial.
AB  - BACKGROUND: Radical inguinal lymphadenectomy (ILND) for metastatic melanoma is
      associated with a high complication rate. Seroma is often the first postoperative
      complication, followed by prolonged wound healing sometimes requiring
      reoperation, infection, multiple outpatient visits and re-hospitalization.
      Prevention of seroma may, therefore, lead to a reduction in many of the other
      complications. METHODS/DESIGN: The primary aim of this randomized study is to
      investigate whether fewer patients require treatment for seroma by immediate
      prophylactic application of incisional, Negative-pressure Wound Therapy (iNPWT)
      following ILND, compared to standard postoperative treatment. The secondary
      outcomes include surgical-site infection, dehiscence, hematoma, length of
      hospitalization, quality of life, safety, long-term assessment of lymphedema and
      non-inferiority oncological outcome. Data will be registered prospectively at
      check-ups after 7 and 14 days, 1 and 3 months and 2 years after inguinal
      lymphadenectomy using case report forms and questionnaires and stored in a secure
      online database. DISCUSSION: To our knowledge, this trial is the first randomized
      study evaluating negative-pressure wound therapy as a prophylactic intervention
      for complications following melanoma-related ILND. The results from this trial
      will hopefully determine the efficacy and safety of prophylactic iNPWT treatment
      in prevention of the clinical relevant short- and long-term postoperative
      complications following ILND and may provide an evidence base for the an improved
      postoperative regimen. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03433937 .
      Prospectively registered on 15 February 2018.

PMID- 30111379
TI  - Rectal perforation following paclitaxel and carboplatin chemotherapy for advanced
      ovarian cancer: a case report and review of the literature.
AB  - BACKGROUND: Paclitaxel is a chemotherapy drug commonly used in the management of
      ovarian cancer. Colonic perforation is an extremely rare complication of
      paclitaxel administration with few case reports in the medical literature. We
      report a case of a patient with advanced ovarian cancer who had a rectal
      perforation following administration of paclitaxel. There has only been one other
      case report of rectal perforation in the medical literature following paclitaxel
      therapy. CASE PRESENTATION: A 55-year-old Caucasian woman with advanced ovarian
      cancer awaiting elective debulking surgery for her tumor presented to our
      emergency department with abdominal pain, vomiting, and diarrhea. She was
      admitted to hospital for neoadjuvant chemotherapy and management of her systemic
      symptoms. She became acutely unwell following one cycle of chemotherapy with
      paclitaxel. A computed tomography scan of her abdomen showed typhlitis of her
      descending colon and a corresponding rectal perforation. Surgical intervention
      was deemed inappropriate as she had a heavy burden of disease and neutropenia.
      She died following a period of conservative management with strong intravenously
      administered antibiotics. CONCLUSIONS: This case highlights the importance of
      recognizing gastrointestinal complications following chemotherapy and the need to
      be aware of the possibility of bowel perforation. Prompt surgical review and
      intervention must be requested in patients with acute abdominal pain and
      persistent gastrointestinal symptoms such as diarrhea and vomiting.

PMID- 30111382
TI  - Sources of confounding in life course epidemiology.
AB  - In epidemiologic analytical studies, the primary goal is to obtain a valid and
      precise estimate of the effect of the exposure of interest on a given outcome in
      the population under study. A crucial source of violation of the internal
      validity of a study involves bias arising from confounding, which is always a
      challenge in observational research, including life course epidemiology. The
      increasingly popular approach of meta-analyzing individual participant data from
      several observational studies also brings up to discussion the problem of
      confounding when combining data from different populations. In this study, we
      review and discuss the most common sources of confounding in life course
      epidemiology: (i) confounding by indication, (ii) impact of baseline selection on
      confounding, (iii) time-varying confounding and (iv) mediator-outcome
      confounding. We also discuss the issue of addressing confounding in the context
      of an individual participant data meta-analysis.

PMID- 30111381
TI  - How do the experiences and beliefs of adults and children with heterozygous
      familial hypercholesterolaemia influence their adherence to treatment? A
      systematic review of qualitative evidence protocol.
AB  - BACKGROUND: Heterozygous familial hypercholesterolaemia (FH) is a genetic
      disorder characterised by elevated levels of low density lipoprotein (LDL)
      cholesterol from birth, estimated to affect 1 in 250 of the UK population. Left
      untreated, FH substantially increases an individual's risk of premature coronary
      heart disease (CHD) and associated mortality. This risk can be minimised with
      timely diagnosis and successful treatment with medication and lifestyle changes,
      as advocated in national and international guidelines. Despite these
      recommendations, the limited research available suggests adherence to treatment
      may be sub-optimal. This review will identify and synthesise the available
      qualitative research regarding the experiences and beliefs of adults and children
      with FH in relation to their condition and its treatment, and the influence of
      these upon treatment adherence. METHODS: The following electronic databases will
      be searched from their inception: Cochrane library, MEDLINE, Embase, PsycINFO
      (via OVID) and CINAHL. Studies available in English and reporting primary
      qualitative data will be included. Database searching will be supplemented with
      searches in relevant specialist websites. The references of identified papers
      will also be hand searched. Two reviewers will independently screen titles and
      abstracts of identified studies, with full texts of potentially relevant papers
      retrieved for review against pre-defined inclusion and exclusion criteria. The
      Critical Appraisal Skills Programme (CASP) Qualitative Research checklist will be
      used to assess quality of the included studies, and the results will be taken
      into consideration when reporting the findings. A data extraction tool will be
      created for use in this review to extract study findings relevant to the review
      questions. A thematic synthesis approach will be taken to analyse the results.
      DISCUSSION: Adherence to treatment recommendations is crucial for the successful
      management of FH and subsequent decrease in risk of CHD later in life. Common
      identified themes could provide an understanding of the beliefs and experiences
      which influence adherence to treatment recommendations and provide an insight
      into perceived barriers and facilitators. The findings are intended to be used in
      the development of future interventions or guidelines regarding treatment of
      children and adults with FH. SYSTEMATIC REVIEW REGISTRATION: PROSPERO
      registration number: CRD42018085946.

PMID- 30111383
TI  - Nosocomial outbreak of vanD-carrying vancomycin-resistant Enterococcus faecium.

PMID- 30111380
TI  - Clinical signs and symptoms in a joint model of four disease activity parameters
      in juvenile dermatomyositis: a prospective, longitudinal, multicenter cohort
      study.
AB  - BACKGROUND: It is currently impossible to predict the prognosis of patients with
      juvenile dermatomyositis (JDM). The aim of this study was to find clinical
      features most strongly associated with outcome variables in JDM as a first step
      towards tailor-made treatment. METHODS: In a large, prospectively followed,
      multicenter cohort study of 340 patients with JDM, each contributing multiple
      visits, a Bayesian model of disease activity was developed, using the four
      continuous outcome variables creatine kinase (CK), childhood myositis assessment
      score (CMAS), manual muscle testing of 8 muscle groups (MMT8) and the physician's
      global assessment of disease activity (PGA). Covariates were clinical signs and
      symptoms. Correlations among visits of the same patient were resolved by
      introducing subject-specific random effects. RESULTS: Myalgia and dysphonia were
      associated with worse disease activity according to all outcome variables.
      Periorbital rash, rash on the trunk, rash over large joints, nail fold changes
      and facial swelling were associated with higher PGA. Notably, periorbital rash
      was also associated with higher CK and lower CMAS and nail fold changes with
      lower CMAS. Contractures were associated with lower CMAS and MMT8 and higher PGA.
      Patients with higher CMAS exhibited a higher MMT8 as well. PGA had the highest
      probability among the four outcome variables of being abnormal even if the other
      three outcome variables were normal. CONCLUSIONS: The signs and symptoms
      associated with disease activity could be used to stratify patients and adapt
      treatment plans to disease activity. The correlation between CMAS and MMT8 and
      the unique information captured by PGA implied that PGA should be maintained as
      an outcome variable, whereas CMAS and MMT8 might be simplified.

PMID- 30111384
TI  - An evaluation and exploration of Irish food-service businesses' uptake of and
      attitudes towards a voluntary government-led menu energy (calorie) labelling
      initiative.
AB  - OBJECTIVE: To investigate the uptake of and attitudes towards a voluntary
      government-led energy (calorie) menu labelling initiative in Ireland among a
      representative sample of food-service businesses and to inform further actions
      that may need to be undertaken to facilitate successful implementation. DESIGN: A
      mixed-methods approach, incorporating a national telephone survey, structured
      observation visits and semi-structured interviews. SETTING: Twenty-six counties
      in the Republic of Ireland. SUBJECTS: A random selection of food-service
      businesses (n 604) participated in the telephone survey. Businesses which
      indicated that they did display calories were selected to participate in
      structured observation visits (n 42), along with a random sample (n 38) of
      businesses that did not display calories. A purposive sample of thirteen food
      service business owners who participated in the telephone survey participated in
      semi-structured interviews. RESULTS: In the telephone survey, 7 % (n 42) of food
      businesses reported displaying calories and the observation visits revealed that
      of these businesses, 10 % (n 4) were not displaying calorie information. Three
      major themes emerged from the semi-structured interviews: uncertainty, impact on
      business and consumer nutrition knowledge. Participants expressed concerns
      regarding inaccuracies in the calorie information, cost and time implications,
      mistrust in the food-service industry and poor nutritional knowledge among
      consumers. These concerns impeded the implementing of calorie menu labelling.
      CONCLUSIONS: A multifactorial approach that incorporates guidance and support
      (training/tax incentives), practical assistance (user-friendly calorie
      calculation software), a reasonable legislative structure and a standardised
      monitoring system is needed to facilitate the successful implementation of
      calorie menu labelling.

PMID- 30111385
TI  - Intramuscular fat content in different muscles, locations, weights and genotype
      sexes and its prediction in live pigs with computed tomography.
AB  - Intramuscular fat (IMF) content depends on sex, genotype and diet and varies with
      pig growth. The aim of the present work was to determine the evolution of IMF by
      genotype-sex, muscle and muscle location, to determine relationships between IMF
      content of different muscles and to predict IMF in live pigs with computed
      tomography (CT). For this purpose, 155 pigs of seven combinations of genotype-sex
      were CT scanned and slaughtered at 70, 100 and 120 kg. From the carcasses, fat
      thickness was measured at several locations along the midline. Loin samples from
      three anatomical positions (between the eighth and ninth last ribs, between the
      third and fourth last ribs and between the third and fourth lumbar vertebrae) and
      three ham muscles (biceps femoris, semimembranosus and gluteus medius) were
      extracted, weighed and IMF was determined with near-IR equipment. From CT images,
      the distribution of volume by Hounsfield value (unit related with the density)
      was obtained for each muscle and anatomical location. Marbling was evaluated in
      the three loin locations. The effects of genotype-sex and live weight and their
      interaction were included in the statistical model. For prediction of IMF with CT
      images, partial least square regression was used. The results show differences in
      IMF content by genotype-sex and muscle. In general, the most cranial part of the
      loin presented higher IMF content, as well as the biceps femoris muscle of the
      ham. Depending on the genotype-sex, IMF content increased during all growth or
      increased until 100 kg and then became constant. Correlation coefficients between
      IMF content by muscle/location were between 0.74 and 0.83 within loin locations
      and between 0.53 and 0.70 for ham muscles. Correlation coefficients between
      marbling and IMF content evaluated at the same location varied between 0.51 and
      0.66. Prediction of IMF content from CT images is not accurate enough (residual
      predictive deviation statistical values lower than 1.3). Muscle weight increase
      with animal growth and allometric coefficients varied between 0.89 and 0.97 for
      the muscles evaluated. The conclusions of the present work are that IMF content
      differs between and within muscle, during growth and by genotype-sex and that
      prediction of IMF in CT images of live pigs is not accurate.

PMID- 30111386
TI  - Maternal smoking and low family income during pregnancy as predictors of the
      relationship between depression and adiposity in young adults.
AB  - There is an increasing incidence of overweight/obesity and mental health
      disorders in young adults and the two conditions often coexist. We aimed to
      investigate the influence of antenatal and postnatal factors that may underlie
      this association with a focus on maternal prenatal smoking, socio-economic status
      and gender. Data from the Western Australian Pregnancy Cohort (Raine) Study
      (women enrolled 1989-1991) including 1056 offspring aged 20 years (cohort
      recalled 2010-2012) were analyzed (2015-2016) using multivariable models for
      associations between offspring depression scores (DASS-21 Depression-scale) and
      body mass index (BMI), adjusting for pregnancy and early life factors and
      offspring behaviours. There was a significant positive relationship between
      offspring depression-score and BMI independent of gender and other psychosocial
      covariates. There was a significant interaction between maternal prenatal smoking
      and depression-score (interaction coefficient=0.096; 95% CI: 0.006, 0.19,
      P=0.037), indicating the relationship between depression-score and BMI differed
      according to maternal prenatal smoking status. In offspring of maternal prenatal
      smokers, a positive association between BMI and depression-score
      (coefficient=0.133; 95% CI: 0.05, 0.21, P=0.001) equated to 1.1 kg/m2 increase in
      BMI for every 1standard deviation (8 units) increase in depression-score.
      Substituting low family income during pregnancy for maternal prenatal smoking in
      the interaction (interaction coefficient=0.091; 95% CI: 0.01, 0.17, P=0.027)
      showed a positive association between BMI and depression score only among
      offspring of mothers with a low family income during pregnancy
      (coefficient=0.118; 95% CI: 0.06, 0.18, P<0.001). There were no significant
      effects of gender on these associations. Whilst further studies are needed to
      determine whether these associations are supported in other populations, they
      suggest potentially important maternal behavioural and socio-economic factors
      that identify individuals vulnerable to the coexistence of obesity and depression
      in early adulthood.

PMID- 30111387
TI  - Sex-specific effects of maternal and postweaning high-fat diet on skeletal muscle
      mitochondrial respiration.
AB  - Exposure to maternal over-nutrition in utero is linked with developmental
      programming of obesity, metabolic syndrome and cardiovascular disease in
      offspring, which may be exacerbated by postnatal high-fat (HF) diet. Skeletal
      muscle mitochondrial function contributes to substrate metabolism and is impaired
      in metabolic disease. We examined muscle mitochondrial respiration in male and
      female mice exposed to maternal HF diet in utero, followed by postweaning HF diet
      until middle age. After in utero exposure to maternal control (Con) or HF diet
      (45% kcal fat; 39.4% lard, 5.5% soybean oil), offspring were weaned to Con or HF,
      creating four groups: Con/Con (male/female (m/f), n=8/8), Con/HF (m/f, n=7/4),
      HF/Con (m/f, n=9/6) and HF/HF (m/f, n=4/4). Oxidative phosphorylation (OXPHOS)
      and electron transfer system (ETS) capacity were measured in permeabilized
      gastrocnemius bundles. Maternal HF diet increased fasting glucose and lean body
      mass in males and body fat percentage in both sexes (P?0.05). Maximal adenosine
      diphosphate-stimulated respiration (complex I OXPHOS) was decreased by maternal
      HF diet in female offspring (-21%, P=0.053), but not in male (-0%, P>0.05).
      Sexually divergent responses were exacerbated in offspring weaned to HF diet. In
      females, OXPHOS capacity was lower (-28%, P=0.041) when weaned to high-fat
      (HF/HF) v. control diet (HF/Con). In males, OXPHOS (+33%, P=0.009) and ETS (+42%,
      P=0.016) capacity increased. Our data suggest that maternal lard-based HF diet,
      rich in saturated fat, affects offspring skeletal muscle respiration in a sex
      dependent manner, and these differences are exacerbated by HF diet in adulthood.

PMID- 30111388
TI  - Strategies to reduce non-communicable diseases in the offspring: negative and
      positive in utero programming.
AB  - Non-communicable diseases (NCDs) are a major problem as they are the leading
      cause of death and represent a substantial economic cost. The 'Developmental
      Origins of Health and Disease Hypothesis' proposes that adverse stimuli at
      different life stages can increase the predisposition to these diseases. In fact,
      adverse in utero programming is a major origin of these diseases due to the high
      malleability of embryonic development. This review provides a comprehensive
      analysis of the scientific literature on in utero programming and NCDs
      highlighting potential medical strategies to prevent these diseases based upon
      this programming. We fully address the concept and mechanisms involved in this
      programming (anatomical disruptions, epigenetic modifications and microbiota
      alterations). We also examine the negative role of in utero programming on the
      increased predisposition of NCDs in the offspring, which introduces the passive
      medical approach that consists of avoiding adverse stimuli including an unhealthy
      diet and environmental chemicals. Finally, we extensively discuss active medical
      approaches that target the causes of NCDs and have the potential to significantly
      and rapidly reduce the incidence of NCDs. These approaches can be classified as
      direct in utero programming modifications and personalized lifestyle pregnancy
      programs; they could potentially provide transgenerational NCDs protection.
      Active strategies against NCDs constitute a promising tool for the reduction in
      NCDs.

PMID- 30111390
TI  - [Expression and Significance of PTEN and Survivin in Acute Lymphoblastic
      Leukemia].
AB  - OBJECTIVE: To explore expression and significance of phosphatase and tensin
      homolog deleted on chromosome ten (PTEN) and survivin in acute lymphoblastic
      leukemia (ALL). METHODS: Peripheral blood samples were collected from 68 patients
      with ALL in our hospital including 48 newby diagnosed patients, 13 patients in
      remission, 7 patients in relapse, and 20 healthy volunteers (control). The
      expressions of PTEN and survivin mRNA and protein were detected by real time PCR,
      Western blot and respectively, and clinical pathological parameter was analyzed.
      RESULTS: The expressions of PTEN mRNA and protein in newby diagnosed, remission
      and relapsed group were lower than that in control group (P<0.01). The
      expressions of PTEN mRNA and protein in newly diagnosed and relapsed groups were
      lower than that in remission group (P<0.01). The expressions of survivin mRNA and
      protein in newly diagnosed, remission and relapsed group were higher than that in
      control group (P < 0.01). The expressions of survivin mRNA and protein in newly
      diagno sed and relapsed groups were higher than that in remission group (P <
      0.01). The expressions of PTEN and survivin mRNA did not relahed with the age,
      sex and white blood count in ALL patients, and also did not related with the
      morphological classification in newly diagnosed ALL (P>0.05), but related with
      immunological calssification in newly diagnosed ALL (P < 0.01). The expressions
      of PTEN and survivin were negatively correlated in ALL (P < 0.01). CONCLUSION:
      PTEN and survivin play an important role in the occurrence, development and
      prognosis in ALL, and may be one of the potential targets for ALL treatment.

PMID- 30111389
TI  - [Study on Immunophenotypes and Gene of Acute Lymphoblastic Leukemia].
AB  - OBJECTIVE: To retrospectively analyze the immunophenotyping, fusion gene and gene
      mutation of 30 acute lymphoblastic leukemia (ALL) cases and to investigate the
      relationship between the analysis results and the clinical therapeutic effect and
      prognosis. METHODS: Thirty All phtients were collected from the First Hospital of
      Harbin, Institute of Hematology and Oncology Department of Pediatrics from August
      2015 to June 2016. According to the classification of FAB standard, 27 cases were
      B system ALL, 3 cases were T system ALL. All patients were diagnosed by bone
      marrow cell morphology, immunophenotype, cytogenetics and molecular biology
      detetions, the differentiation antigens on membrane surface and in cytoplasm of
      ALL cells, and 43 kinds of fusion gene qualitative screening(BCR-ABL, AML1-ETO,
      PML-RARalpha and so on) were qualitative screened and ALL gene mutations(IKZF1,
      TP53, PAX5, JAK1, JAK2, CRLF2, PHF6, NOTCH1, FBXW7, PTEN)were detected by next
      generation sequencing(NGS). RESULTS: (1) Among 30 ALL patients, the incidence of
      B-ALL(90.00%) was higher than that of T-ALL(10.00%). (2) 27 cases of B-ALL
      expressed CD19, CD22, CD10, CD34 and so on. CD19 and CD22 were the most
      diagnostic antigens of B-ALL. (3) 3 cases of T-ALL mainly expressed cCD3, CD7,
      CD10, cTDT and so on; cCD3 and CD7 were the most diagnostic antigens of T-ALL.
      (4) The quantitative screening of 30 cases of ALL 43 fusion genes found BCR
      ABL,TEL-AML1 and E2A-PBX1, MLL-AF6, MLL-AF4, and SIL-TAL1 fusion gene was
      positive in 1 case each; NGS detection of gane mutations associated with ALL
      showed that: 3 cases of B-ALL found that TP53 mutation occured 3 casas of B-ALL,
      TET2 I1762V mutations in 1 cases, 3 patients (2 cases of T-ALL, 1 cases of B-ALL)
      showed NOTCH1 gene mutation. After a cycle of treatment, the efficacy of adult B
      ALL treatment (28.57%) was significantly lower than that of child B-ALL (95.00%),
      and the survival rate of child B-ALL was significantly better than that of adult
      B-ALL until July 10, 2017, and the differences were significant. CONCLUSION: The
      immunophenotype technology of leukemia and molecular biology has an important
      guiding role in the diagnosis of leukemia, selection of treatment plan and
      evaluation of curative effect, and it is the complement of bone marrow cell
      morphology diagnosis.

PMID- 30111392
TI  - [All-Trans Retinoic Acid and Decitabine Synergistically Induce Anti-Leukemia
      Effect on U937 Cell Line and Newly Diagnosed Elder AML Patients].
AB  - OBJECTIVE: To investigate the effect of all transretinoicacid(ATRA) combined with
      decitabine (5-Aza-2'-deoxycytidine;DAC) on DNA methylation and gene expression of
      p16INK4a (p16) and retinoic acid receptor beta (RARbeta), and to explore their
      combined anti neoplastic effect on U937 cells and newly diagnose delder acute
      myeloid leukemia(AML) patients. METHODS: The expression levels of p16 and RARbeta
      were determined by qRT-PCR and Western blot. Methylation-specific PCR was used to
      analyze their methylation status. WST-1 and flow cytometry were performed to
      detect growth inhibition, differentiation, apoptosis and cell cycle of U937 cells
      respectively. RESULTS: The expression p16 and RARbeta was down-regulated by
      promoter hypermethylation in newly diagnose delder AML patients and U937 cells.
      Combination treatment of ATRA and DAC induced DNA hypomethylation as well as gene
      expression of p16 and RARbeta, which contributed to the growth inhibition,
      differentiation, apoptosis and cell cycle arrest of U937 cells. In addition for
      elder AML patients intolerable to standard chemotherapy, the combination regimen
      of ATRA and DAC showed antineoplastic activity accompamied by up-regulation of
      p16 and RARbeta expression and decrease of bone marrow blast, moreover the
      parients showed good tolerence to the reginen. CONCLUSION: The regimen of ATRA
      combined with DAC as the combination therapeutic strategy for inducing
      differentiation and demethylation possesses the anti-AML potency, and contributes
      to optimizing the therapeutic strategy for elder AML patients and promoting the
      clinical prognosis.

PMID- 30111391
TI  - [Analysis of Clinical and Laboratory Features of Patients with Acute Myeloid
      Leukemia(AML)-M1/M2 with Cuplike Nuclei Morphology].
AB  - OBJECTIVE: To analyze the clinical and laboratory features of acute myeloid
      leukemia (AML) with cuplike nuclei morphology. METHODS: One hundred and seventy
      patients diagnosed with AML (M1andM2) between December 2009 and December 2016
      were included in the study. Bone marrow smears were prepared for morphologic
      alanalysis, the immunophenotype was analyzed by flow cytometry and the RHG
      banding was for conventional cytogenetic assay (CCA) ,gene mutation was detected
      by sequencing. RESULTS: Among the 170 AMLpatients, 67 were diagnosed as M1 and
      103 patients was diagnosed as M2, 43 patients(25.3%) defined as cuplike nuclei
      positive, among them 38patients (88.4%) were M1 while only 5 patients (11.6%)
      were with M2(P<0.01). No significant value about sex(P> 0.05) between cuplike
      nuclei-positive and -negative group, while older patients were found in cuplike
      nuclei-positive group (P<0.05). Higher peroxydas (POX) ratio (P<0.05) and
      integration (P<0.05) were found in cuplike nuclei- positive group. Furthermore,
      the patients with cuplike nuclei-positive lack the expressions of CD34 (P<0.01)
      and HLA-DR(P<0.01) while no other immunophenotype markers were found. Among the
      152 patients (89.4%) for genetic analysis ,83.8% karyotype of the cuplike nuclei
      positive group were normal while only 54.8 of negative group was normal by CCA.
      Molecular biology analysis showed that the patients in cuplike nuclei-positive
      group have significantly highe rNMP1 (P<0.01) and FLT3(P<0.01) mutations as
      compared with the negative group. Furthermore, the relationship of the ratio o
      fcuplike nuclei and the type of gene mutations were investigated, and no
      significant associations were found. However, it was found that the patients with
      FLT3 mutation displayed more biological nuclear invagination than the patients
      with NPM1 mutations (P<0/01). CONCLUSION: AML patients with positive cuplike
      nuclei have characteristic morphological changes, typical immunophenotype with
      HLA-DR- and CD34-, normal karyotype accompanied by NPM1 and FLT3 mutations.

PMID- 30111393
TI  - [Effect of Daunorubicin on Release and Procoagulant Activity of Microparticles
      Derived from Acute Promyelocytic Leukemia Cells].
AB  - OBJECTIVE: To investigate the effect of daunorubicin on the number and
      procoagulant activity of Microparticles derived from acute promyelocytic
      leukemia(APL) cells. METHODS: APL cells were isolated from bone Marrow of 5 newly
      diagnosed APL patients, the bone marrow mononuclear cells were collected from 5
      patients with iron deficiency anemia as control.APL cells were treated with
      different concentration of daunorubicin(0.1,0.5,1.0 and 2.0umol/L) for 24 h.
      Microparticles were extracted from the cell culture medium for qualitative
      anaysis of the extracted microparticles.The morphologic features of the
      microparticles were observed by transmission electron microscopy.The number of
      microparticles was detected by flow cytometry.The procoagulant activity of
      microparticles was measured by recalcification time assays. RESULTS: Under a
      transmission electron microscope, theextracted microparticles took a round or
      oval morphology with a transparent center,and their diameters were arund 100nm,
      consistent with the morphological characteristics of microparticles. Compared
      with bone marrow mononuclear cells-derived microparticles,the counts of the bone
      marrow APL cells-derived microparticles significantly
      increased(P<0.05).Daunorubicin increased the shedding of microparticles in a dose
      dependent manner(r=0.73,P<0.01).Compared with normal bone marrow mononuclear
      cells-derived microparticles,bone marrow APL cells-derived microparticles showed
      higher procoagulant activity(P<0.05).Daunorubicin treatment enhanced the
      prccoagulant activity of APL cells-derived microparticles which paralleled the
      increasing drug concentrations(r=-0.78,P<0.01). CONCLUSION: Daunorubicin can
      promote the release of APL cells-derived microparticles and enhance their related
      procoagulan activity.

PMID- 30111394
TI  - [Long Non Coding RNA RP11-69I8.3 Expression in Acute Leukemia and Its Cinical
      Significance].
AB  - OBJECTIVE: To investigate the expression of long non coding RNA RP11-69I8.3 in
      acute leukemia and its clinical significance. METHODS: lncRNA RP11-69I8.3
      expression was detected by RT-PCR in bone marrow samples from 17 healthy
      controls, 32 newly diagnosed AML patients and 32 newly diagnosed ALL patients,
      and 25 ALL patients of complete remission after chemotherapy. Meanwhile, the
      clinical data were collected and the relation of lncRNA RP11-6918.3 expression
      with the clinical characteristics was analyzed. RESULTS: Compared with the
      control group, there was no significant difference in the expression of lncRNA
      RP11-69I8.3 in AML group(P>0.05). lncRNA RP11-69I8.3 lowly expressed in untreated
      ALL group(P=0.001). Compared with the de novo ALL group, lncRNA RP11-69I8.3 was
      highly expressed in complete remission ALL group (P<0.013). In 32 de novo ALL
      patients,the expression of lncRNA RP11-69I8.3 in children was significantly lower
      than that in adult(P=0.017). There was no correlation of the expression of lncRNA
      RP11-69I8.3 with the sex, WBC count, HB level, Plt count, LDH level, T or B type,
      ratio of bone marrow blast cell, BCR/ABL and WT1 fusion gene expression,
      chromosome karyotype, extramedullary infiltration, whether complete remission
      after one chemotherapy, whether relapse. In 26 B-ALL patients, there was no
      correlation between lncRNA RP11-69I8.3 and the immunophenotype. CONCLUSION: The
      expression of lncRNA RP11-69I8.3 in the untreated AML is not significantly
      different from the control group. lncRNA RP11-69I8.3 is low expressed in ALL
      group, highly expressed in ALL group with complete remission. In untreated ALL,
      the expression of lncRNA RP11-69I8.3 in children is significantly lower than that
      in adult. In B-ALL patients, the lncRNA RP11-69I8.3 is not relevant with the
      immunophenotype.

PMID- 30111395
TI  - [Expression and Clinical Significances of HGFA, Matriptase, HAI-1 and HAI-2 in
      Acute Myeloid Leukemia].
AB  - OBJECTIVE: To investigate the expression and clinical significances of HGFA,
      Matriptase, HAI-1 and HAI-2 in patients with acute myeloid leukemia (AML).
      METHODS: The bone marrow samples from 91 AML patients, 41 AML patients in
      complete remission, and 32 normal controls were collected. Real time fluorescence
      quantitative RT-PCR (qRT-PCR) was used to detect the mRNA expressions levels of
      HGFA, Matriptase, HAI-1, HAI-2 . The expressions of these genes were compared
      among AML untreated group, the complete remission group and the healthy control
      group. The correlation of their expression with clinical characteristics was
      analyzed. RESULTS: The level of HGFA in the AML untreated group was higher than
      that in the healthy control group(P<0.05), while the HAI-2 mRNA level was lower
      than that in the healthy control group(P<0.05). The mRNA levels of HAI-1 and
      Matriptase were not changed significantly in all groups. The HAI-2 mRNA
      expression level was significantly lower in the high white blood cell group
      (P<0.05). CONCLUSION: The abnormal activation of HGF/c-Met signaling system in
      AML may result from the increase of HGFA expression and the decrease of HAI-2
      expression of the upstream regulatory factors.

PMID- 30111396
TI  - [Lymphocyte Count before First Consolidation Therapy Is A Predictor of Relapse
      free Survival in Acute Myeloid Leukemia].
AB  - OBJECTIVE: To investigate the effects of absolute lymphocyte count(ALC) before
      start of the first cycle of consolidation chemotherapy(CC) on the relapse free
      survival in the patients with acute myeloid leukemia(AML), so as to explore a
      simple and easy method for predicting AML relapse. METHODS: The clinical data of
      132 patients with newly diagnosed AML (all non-acute promyelotic leukemia) from
      2011 to 2017 were analyzed retrospectively. The 132 AML patients were treated
      with standard induction chemotherapy (IC) and consolidation chemotherapy (CC).
      According to lymphocyte count of patients before start of the first cycle of CC,
      the AML patients were divided into 2 group: high lymphocyte count group (H
      Lym>=1.2*109/L) and low lymphocyte count group (L-Lym<1.2*109/L). The differences
      in ralapse rate and relapse-free survival between 2 groups were analyzed.
      RESULTS: Among 132 patients with AML, patients who could be valuated and were
      elicible for the study accounted for 65 (49.24%). The absolute leukocyte count,
      age, chromosome karyotypes before IC of patients did not show statistical
      difference between H-Lym group (40 cases) and L-Lym group (25 cases). Unvarvate
      analysis showed that the Low lymphocyte count and unfavorable chromosome
      karyotypes were poor prognostic factors for the relapse-free survival time, and
      there was significant difference between 2 groups (P<0.01). The relapse risk in
      patients of L-Lym group increased, the hazard ratio (HR)=3.01 (95% CI=1.55-4.98)
      (P<0.01). In multivariate analysis containing unfavorable prognostic karyotypes,
      this trend still existed (HR=2.52, 95% CI 1.28-9.98)(P<0.01). CONCLUSION: The AML
      patients with high lymphocyte count before the first CC have more long relapse
      free survival time suggesting that the lymphocyte count before the first CC may
      be prognostic factor for relapse free survival of AML patients.

PMID- 30111397
TI  - [Effect of Leukodepleted Blood Transfusions on the Balance of Th1/Th2 Cells in
      Peripheral Blood of Patients with Acute Lymphoblastic Leukemia].
AB  - OBJECTIVE: To investigate the effect of leukodepleted blood transfusions on
      peripheral blood Th1/Th2 cell balance in patients with acute lymphoblastic
      leukemia (ALL). METHODS: Fifty-seven ALL patients in our hospital from March 2016
      to August 2017 were selected, 31 of them received routine blood transfusion were
      enrolled in group A, and 26 patients received depleted-blood leukotransfusion
      were enrolled in group B, 36 cases in normal physical examination at the same
      period were enrolled in control group. And the basic clinical characteristics of
      patients were recorded; the ratio of Th1/Th2 cells in peripheral blood of
      patients was analyzed by flow cytometry;the serum levels of IL-2, IFN-gamma, IL
      4, IL-10 were detected by ELISA method; the mRNA levels of T-bet and GATA-3 in
      lymphocytes were detected by RT-PCR;the protein levels of T-bet and GATA-3 in
      lymphocyte were detected by Western blot. RESULTS: The Th1/Th2 ratio in
      peripheral blood of ALL patients significantly related with patient age and risk
      grade (P<0.05).After treatment,the change of Th1/Th2 ratio in group A showed no
      statistical difference from Th1/Th2 ratio before treatment (P>0.05), while the
      Th1/Th2 ratio in group B increased (P<0.05);the levels of IL-2, IFN-gamma, IL-4
      and IL-10 secreted from Th1 and Th2 cells of ALL patients in A group were not
      changed significantly(P>0.05), while the levels of IL-2 and IFN-gamma secreted
      from Th1 cells of ALL patients in group B increased, the levels of IL-4 and IL-10
      secreted from Th2 cells in group B decreased with statistical difference
      (P<0.05); the RT-PCR and Western blot showed that the expression levels of T-bet
      mRNA and T-bet protein in group A were lower than those in control group, while
      the expression levels of T-bet mRNA and T-bet protein in group B were higher than
      those in group A (P<0.05); the expression levels of mRNA and GATA-3 protein in
      group A were higher than those in control group, the expression levels of mRNA
      and GATA-3 protein in group B were lower than those in group A (P<0.05).
      CONCLUSION: The leukoreduced blood transfusion helps to improve the balance of
      Th1/Th2 cells in peripheral blood and improve the immune function of patients,
      which may closely relate with the expression levels of T-bet and GATA-3.

PMID- 30111398
TI  - [Analysis of Prognostic Factors for 96 Patients with Acute Lymphoblastic
      Leukemia].
AB  - OBJECTIVE: To investigate the clinical characteristics and clinical prognostic
      factors of patients with acute lymphoblastic leukemia (ALL). METHODS: Ninety-six
      ALL patients in our hospital from June 2012 to August 2014 were selected and
      their clinical data were collected. The related clinical data of patients were
      recorded, and the relation between clinical characteristics and therapeutic
      efficacy was analyzed. The COX analysis was used to reveal the risk factors
      affecting the patient's OS and DFS time. RESULTS: Among 96 ALL patients, 65
      patients achieved complete remission (CR) after treatment. The age,
      immunophenotype, central nervous system leukemia (CNSL) and peripheral blood WBC
      count correlated with complete remission (P<0.05). The age, WBC count, platelet
      level, immune typing and consolidation therapy were the prognostic factors
      (P<0.05), the 2 year OS rate was influenced by age, WBC count, CD34 and
      consolidation therapy (P<0.05), the 2 year DFS rate was influenced by age, CD34
      and consolidation therapy (P<0.05). CONCLUSION: Age, WBC counts, CD34 and
      consolidated treatment after remission are prognostic factors for ALL patients,
      which has guiding significance for clinical treatment of ALL.

PMID- 30111399
TI  - [Analysis of Factors Influencing Prognosis of 87 Adults with Ph Chromosome
      Negative ALL].
AB  - OBJECTIVE: To explore the factors influencing total complete remission (CR),
      recurrence, disease-free survival (DFS) rate and overall survival (OS) rate in
      adults with Philadelphia (Ph) chromosome negative acute lymphoblastic leukemia
      (ALL) and the effect of subsequent allogeneic hematopoietic stem cell
      transplantation (allo-HSCT) on prognosis. METHODS: The clinical data of 87 adult
      patients with Ph negative ALL were retrospectively analyzed, the CHOP regimen
      plus L-asparaginase (L-Asp) was used for the induction therapy, and the CHOP+
      modified Hyper-CVAD or methotrexate was set up as the consolidation chemotherapy
      regimen. After consolidation chemotherapy for 3-6 courses, 45 patients (51.72%)
      received allo-HSCT , and 42 patients (48.28%) continually received the maintained
      consolidation chemotherapy. The average follow up time of the surviving patients
      was 40.13 (3-60 months). RESULTS: Out of 87 patients with Ph-ALL one patient died
      (1.15%). In 86 patients who could be evaluated, 68 cases (79.67%) reached CR at
      the end of 1 course, 80 cases obtained CR (93.02%). Multivariate regression
      analysis showed that the enlargement of lever, spleen and lymphomode, WBC count>=
      100*109/L were affecting factors for total CR (P<0.05). Among 80 cases with CR,
      27 cases (33.75%) relapsed, 5 years' overall survival (OS) rate and disease-free
      survival (DFS) rate were 47.50% and 45.00% respectively. Multivariate regression
      analysis yet showed that the induction chemotherapy without L-Asp, presence of
      CNS leukemia at diagnosis, absence of allo-HSCT and no CR after indution
      chemotherapy for 4 weeks were affecting factors for relapse and poor prognosis of
      patients (P<0.05). According to 4 prognostic factors such as presence of CNS
      leukemia or no, WBC count>=100*109/L or no, induction chemotherapy with L-Asp or
      no and CR after induction chemotherapy for 4 weeks or no, 86 patients were
      divided into low-risk group (without poor prognostic factor), middle-risk group
      (with 1 poor prognostic factor), high-risk group (with 2-4 poor prognostic
      factors). Statistical results showed that allo-HSCT treatment in low-risk group
      had no significant effect on OS and DFS (P>0.05). The rate of OS and DFS in
      middle and high-risk group were significantly higher than those of patients
      without allo-HSCT treatment (P<0.05). CONCLUSION: Patients with central nervous
      system leukemia, high white blood cell count (>=100*109/L), induction
      chemotherapy without L-Asp, no CR after 4 weeks of chemotherapy and absence of
      allo-HSCT treatment are the factors influencing the prognosis of adult patients
      with Ph negative ALL, so the patients with those poor prognostic factors should
      take active treatment of allo-HSCT.

PMID- 30111400
TI  - [Effects of Osthole on Apoptosis of HL-60 Cells Induced by TRAIL and Its Related
      Mechanism].
AB  - OBJECTIVE: To explore the effects of Osthole on apoptosis of HL-60 cells induced
      by tumor necrosis factor related apoptosis inducing ligand (TRAIL) and its
      possible mechanism. METHODS: The proliferative inhibition of HL-60 cells treated
      with different concentrations of Osthole, TRAIL alone and Osthole combined with
      TRAIL was measured by MTT assay. The HL-60 cells were treated with Osthole, TRAIL
      alone and Osthole combined with TRAIL at the concentration<IC50value, i.e.
      100umol/L for Osthole and 40 ng/ml for TRAIL. Apoptosis and mitochondrial
      membrane potential (MMP) of HL-60 cells were detected by flow cytometry; the mRNA
      expression of BCL-2, BAX and DR5 was determined by RT-PCR; and the levels of
      Caspase-3,-8,-9 activity were detected by spectrophotometry. RESULTS: The
      combined treatment (100umol/L Osthole + 40 ng/ml TRAIL) of HL-60 cells for 48 h
      induced an apoptotic rate of (33.9+/-2.7) %, which was significantly higher than
      that of cells treated with Osthole or TRAIL alone (P<0.05); at the same time, the
      combined treatment promoted the decrease of MMP and the expression rate of BCL
      2/BAX, and potentiated the expression of DR5 and Caspase-3,-8,-9 activity.
      CONCLUSION: Osthole can sensitize HL-60 cells to TRAIL-induced apoptosis, which
      may be related with the activation of mitochondrial pathways and up-regulation of
      DR5.

PMID- 30111401
TI  - [Apoptosis Effects of GM3 Ganglioside on U266 Cells and Its Possible Mechanism].
AB  - OBJECTIVE: To investigate the proliferation- inhibitory and apoptosis inducing
      effect of ganglioside GM3 on human multiple myeloma cell line U266 cells and its
      possible mechanisms. METHODS: MTT assay and flow cytometry were used to observe
      the effects of GM3 ganglioside on proliferation and apoptosis of human myeloma
      cell line U266. Effects of different concentration of ganglioside GM3 on the mRNA
      expression level of BCL-2 and BAX were detected by Real-time PCR. RESULTS: MTT
      assay and Flow Cytometry showed that ganglioside GM3 could induce the apoptosis
      and inhibit the proliferation of multiple myeloma U266 cell line, and both the
      effects were enhanced with the increase of GM3 ganglioside concentration.
      Compared with the control group, the relative expression of BAX mRNA with the
      increase of GM3 concentration in experimental group was enhanced
      gradually(r=0.968), while the relative mRNA expression of anti-apoptotic gene BCL
      2 was decreased gradually(r=-0.727). CONCLUSION: GM3 ganglioside can induce
      apoptosis and inhibit the proliferation of U266 cell line in a concentration
      dependent manner. The mechanism may be related with up- regulation of BAX
      expression and down-regulation of BCL-2.

PMID- 30111402
TI  - [Knockout of BMAL1 Gene Induces Apoptosis of HL-60 Cells and Inhibits its
      Proliferation].
AB  - OBJECTIVE: To explore the biological function of BMAL1 in human acute myeloid
      leukemia by means of the HL-60 cell line in whica circadian gene BMAL1 was
      konocked-out by the CRISPR/Cas9 technology. METHODS: Two sgRNAs for BMAL1 were
      designed and the PX459 knockout vectors containing the sgRNA were constructed.
      The activity of 2 sgRNAs was detected by T7 endonuclease I. the BMAL1 knocked out
      HL-60 cells were prepared by transient transfection of the target vectors into
      the cells. Western blot was used to detect the expression of BMAL1 protein. The
      apoptosis of the targeted cells was detected by flow cytometry. The proliferation
      status of the cells was assessed by the CCK-8 assay. RESULTS: The PX459-sgRNA
      vectors were successfully constructed and screened to assure the activity of the
      targeting vector. It was found that the expression of BMAL1 protein was not
      detected in BMAL1-knocked out HL- 60 cells. Further, it was shown that BMAL1
      knockdout could promote the apoptosis of HL-60 cells and inhibit the cell
      proliferation ability. CONCLUSION: BMAL1 knocked out HL-60 cells have bean
      successfully established using the CRISPR/Cas9 gene editing technique, and BMAL1
      knockout can promote the HL-60 cell apoptosis and inhibit its proliferation.These
      result reveal the biological role of the BMAL1 circadian gene in acute myeloid
      leukemia.

PMID- 30111403
TI  - [Safety and Efficacy of VDMP Re-induction Regimen in Chinese Children with
      Relapsed Acute Lymphoblastic Leukemia-A Report from Jiangsu Childhood Hematology
      Group].
AB  - OBJECTIVE: To evaluate the therapeutic safety and efficacy of VDMP re-induction
      regimen in Chinese children with relapsed acute lymphoblastic leukemia (ALL).
      METHODS: Forty-one patients with relapsed ALL were prospectively enrolled in this
      study. All the patients were distributed in 3 children's hospitals and treated
      with VDMP regimen as the first re-induction chemotherapy. Therapeutic efficacy
      and side-effects were analyzed. RESULTS: The ratio of male to female was 27:14.
      The median age was 7.9 (2.2-15.4) years old. Patients relapsed at very early,
      early, and late stage were 7 cases, 11 cases, and 23 cases, respectively.The
      immunophenotype analysis showed that 38 cases were B-ALL, and 3 cases were T-ALL.
      All patients suffered from grade 4 of neutropenia and forty(97.6%) cases got
      infection, of them one case died. Thirty-nine(95.1%) cases had nonhematologic
      adverse event at least one organ involved grade 3 in 38 out of 41 cases, the VDMP
      therapy was completed, 34(89.5%) cases achieved a complete remission (CR), 1 case
      achieved partial remission(PR), and 3 cases didn't get remission. Follow-up data
      of 38 cases with completing VDMP chemotherapy were obtained, only one case was
      lost. Among 37 cases available for evaluation, 16 cases received allo
      hematopoietic stem cell transplantation(allo-HSCT) after chemotherapy, and 13
      patients survived, while 21 cases did not receive allo-HSCT(treated with
      chemotherapy only), and 8 patients survived.The overall survival rate of allo
      HSCT group was significantly higher than that of those treated with chemotherapy
      only(P<0.05). CONCLUSION: VDMP re-induction regimen is effective and well
      tolerable for pafients in the treated children with relapsed ALL. After
      remission, allo-HSCT is recommended with the aim of long survival.

PMID- 30111404
TI  - [Detection of Gene Abnormalities in 43 Cases of Chronic Lymphocytic Leukemia by
      Fluorescence in Situ Hybridization].
AB  - OBJECTIVE: To explore the value of fluorescence in situ hybridization (FISH) in
      diagnosis and prognosis evaluation of chronic lymphocytic leukemia (CLL).
      METHODS: R banding technique was used for karyotype analysis in 43 cases of CLL,
      and fluorescence in situ hybridization(FISH) technique was used for analysis of 5
      genes in 43 cases of CLL, including D13S25, RB1,ATM, P53 and CEP 12 . RESULTS:
      The detection rate of chromosome abnormality was 9.3% for the 43 cases. The
      chromosome karyotype abnormality was involoved in the number abnormality and the
      structural abnormality, including No. 2, 6, 14, and sex chromosome. The patients
      with normal chromosome karyotype were more common(79.1%). At the same time,
      mitotic figure in 5 CLL patients did not observed. The positive rate of FISH
      detection was 55.8%(24/43). Among which, D13S25 deletion was the highest and
      reached to 37.2%, followed by RB1 deletion(20.9%), CEP 12 amplification(16.3%),
      ATM deletion(9.3%) and P53 deletion(7.0%). In 24 FISH-positive cases, 20 cases
      displayed the normal chromosome karyotype, and in 3 cases the mitotic figure was
      absent. There was only one case of abnormal chromosome, which was not involved in
      the positive gene tested by FISH. CONCLUSION: FISH is an important means of CLL
      genetic detection, which can greatly raise the detection rate of cytogenetics
      abnormalities in CLL, but the probe quantity is limited, so it is necessary to
      use FISH technology combined with chromosome karyotype analysis so as to improve
      the detection rate of abnormal cytogenetics, and provide the basis for the
      clinical diagnosis and prognosis of CLL.

PMID- 30111405
TI  - [Autophagy and Expression of UCH-L3 Induced by Rapamycin in HL-60 Cells].
AB  - OBJECTIVE: The aim of this study was to explore whether rapamycin can induce the
      autophagy of HL-60 cells and UCH-L3 expression. METHODS: Cell proliferation
      activity of HL-60 cells treated with rapamycin was measured by CCK-8 assay. After
      the cells were treated with rapamycin for different time, the fluorescent
      microscopy was used to detect the cells' modality, the morphology of
      autophagosomes was observed by transmission electron microscopy, the mRNA levels
      of autophagy-related genes LC3-II and UCH-L3 were detected by real-time PCR, and
      the Western blot was employed to detect the expression level of UCH-L3. RESULTS:
      Different concentrations of rapamycin could inhibit the proliferation of HL-60
      cells. The inhititory levels in treatment groupall were statistically different
      from those in the control group (P<0.05). Under fluorescent microscopy, the
      fluorescence intensity in the control group was low, but in the treatment groups
      it strengthened along with the extension of process time. After treatmant with
      2umol/L rapamycin for different time (12,24 h), the number of autophagosomes in
      the control group was less , while in the treatment groups was more, the mRNA
      level of LC3-II was raised as compared with the control group, while the mRNA and
      protein level of UCH-L3 declined (P<0.05). CONCLUSION: Rapamycin can inhibit the
      proliferation of HL-60 cells and induce the autophagic death. UCH-L3 may play a
      role in the regulation of autophagic death of leukemia.

PMID- 30111406
TI  - [The Clinical Efficacy of Small Dose CAG Program in Comparison with MA Program in
      Senile Patients with Acute Myeloid Leukemia].
AB  - OBJECTIVE: To compare the clinical efficacy of small dose CAG regimen and MA
      regimen in the senile patients with acute myeloid leukemia(AML). METHODS: The
      clinical data of 83 senile patients with AML from Sep. 2012 to Sep. 2016 in our
      Hospital were analyzed retrospectively. According to the chemotherapy regimens,
      the patients were divided into CAG group and MA group; 36 patients in CAG group
      were treated with small dose CAG, while 47 patients in MA group were treated with
      MA. The curative efficiency(CR rate, PR rate,NR rate and OR rate), side effect
      (myelosuppression,infection,intestinal discomfort and hemorrage), serum
      cytokines(IL-6,IL-17,TGFbeta), and prognosis(survival rate in 2 years, MST and
      SST) were observed, compared and studied in these 2 group. RESULTS: The curative
      efficiency, CR rate and PR rate of the CAG group were not significantly different
      from that of the MA group (P>0.05). The side effect in CAG group was
      significantly lower than that in the MA group (P<0.05). The levels of serum
      cytokines of the MA group were lower than those of the CAG group. Additionally,
      the prognosis was not significantly different between 2 groups(P>0.05).
      CONCLUSION: For senile patients with acute myeloid leukemia, compared with
      traditional MA regimen, the small dose CAG has a certain curative efficacy and
      survival rate, and the incidence of side effect reduced. Therefore, the small
      dose CAG is superior to MA for the senile patients with acute myeloid leukemia.

PMID- 30111407
TI  - [Clinical Characteristics and Prognosis of patients with Variant Philadelphia
      Chromosome Positive Leukemia].
AB  - OBJECTIVE: To study the clinical characteristics and prognosis of patients with
      variant Ph chromosome-positive leukemia. METHODS: The defection of morphology,
      cytogenetics, immunology and molecular biology was performed in 4 cares of
      variant Ph chromosome-positive leukemia, and the therepeuitics outcome of 4
      patients was evaluated. RESULTS: Among 4 cases of variant Ph+ leukemia, 3 cases
      were patients with CML, including 1 case in chronic phase and 2 cases in
      accelerated phase; and 1 cases was patient with adult B acute lymphoblasric
      leukemia(B-ALL).The defecfion of cytogenetics in 4 cases showed that 2 cases of
      CML displayed t(9; 22; 14) abnormality, 1 case of CML displayed t(5; 9; 22)
      abnormality, moreover, the BCR/ABL fution gane in 3 cases of CML all was e14a2
      type, 1 cases of adult B-ALL disylayed t(9; 22; 17) abnormatlity, BCR/ABL fution
      gene of this case was e13a3 type, 4 patients all received treatment wire
      chemotherapeptic regimen contaiming methanesulfanate imatinib. As a result, 1
      cases of adult B-ALL with e13a3 type BCR/ABL fusion gene positive relapsed after
      molecular biology remission for 4 months and died in the 10th month; and yet 3
      cases of CML are still in molecular biology remission, the disease-free survival
      time of these 3 cases was 10, 19 and 27 months respectively. CONCLUSION: The
      patients with variant Ph chromosome-positive leukemia will response to the first
      generation tyrosine kinase inhibitors, but the prognosis of patients with e13a3
      type of BCR/ABL fusion gene remains to be further explored.

PMID- 30111408
TI  - [18F-FDG PET/CT Manifestation and Clinical Analysis of Primary Hepatic Lymphoma].
AB  - OBJECTIVE: To explore the imaging characteristics of 18F-FDG PET-CT and clinical
      presentation of patients with primary hepatic lymphoma (PHL). METHODS: The 18F
      FDG PET-CT image data of 6 patients with pathologically diagnosed PHL, were
      retrospectively analyzed. RESULTS: The six patients included 4 male cases and 2
      female cases, with median age of 65 years old , and all the cases were diagnosed
      as diffuse large B-cell lymphoma. In regarding of 18F-FDG PET-CT imaging, all the
      cases showed hypodense masses and high FDG uptake, with homogenous density in 5
      cases and necrostic area of low density in 1 case. The SUVmax was 6.3, 9.5, 12.8,
      22.1, 28.4, and 33.5, respectively. Three typical PET-CT imaging findings were as
      follows: 4 cases appeared as multiple nodes, 1 case was the type of solitary
      mass, and 1 case was the type of diffuse infiltration. 5 cases showed a mild
      enhancement by CT scanning, and 2 cases displayed "blood vessel floating" in. In
      2 cases, MRI scanning demonstrated low signal intensity on T1WI, and homogeneous
      signal intensity on T2WI with mild enhancement. CONCLUSION: The 18F-FDG PET-CT
      manifestation of PBL has a certain characteristics that can providt helpful to
      diagnose primary hepatic lymphoma.

PMID- 30111409
TI  - [Analysis of Clinical Characteristics for Primary Adrenal Lymphoma].
AB  - OBJECTIVE: To explore clinical characteristics of the Primary Adrenal
      Lymphoma(PAL), so as to enhance the understanding of diagnosis, treatment and
      prognosis of PAL. METHODS: The clinical data of 2 patients with PAL
      retrospectively analyzed and the clinical characteristics were explored in
      combination with releted literalures. RESULTS: Adrenal gland neoplasm was found
      in 2 patients by imaging examination. The pathological type of one case was
      diffuse large B cell lymphoma, the other one was extranodal NK/T-cell lymphoma.
      The former refused to hosipitali3t and the other received to be admited in
      hospital after the definite diagnosis. She died at the 32th day after diagnosis,
      due to the complication with acute pancreatitis before chemotherapy. The latter
      accepted the scheme of"Gemox"combining with the scheme"VP-16+DXM"to control
      hemophagocytic lymphohistiocytosis. The patient's condition deteriorated rapidly
      after a short period of improvement, then died at the 40th day after chemotherapy
      because of multiple organ failure. CONCLUSION: PAL is a rare extra-nodal lymphoma
      with higher malignancy, the combination of chemotherapy and radiotherapy results
      in the best outcome among all the treatments. The prognosis of patients with
      different pathological types was diverse, thus it is very important to choose the
      appropriate treatment according to different pathological types.

PMID- 30111410
TI  - [Clinical Analysis of EB Virus Infection Complicated with Hemophagocytic Syndrome
      and Hodgkin's Lymphoma].
AB  - OBJECTIVE: To investigate the clinical characteristics and outcome of parhents
      with EBV infection conbined with hemophagocytic syndrome and Hodgkin's lymphoma.
      METHODS: The morphotogy of bone marrow cells was observed by bone marrow smear
      and light microscopy, the pathologic changes of bone marrow ware analyzed by bone
      marrow biopsy and immunohistochemistry methord, the pathologic changes of
      lymphonudes ware detected by immunohistochemical methord, the paticnts were
      treated with ABVD (epirubicin, bleomycin, vincristine and dacarbazine)
      chemotherapeutic regimen. RESULTS: Fever complicatid with pancytopenia, obvious
      increase of ferritin and sCD25, hypofibrinogenemia, hemophogocytic phenomen of
      bone marrow, increase of EBV-DNA copy number ware observed, which all accorded
      with the criteria EBV righted hemophagocytic syndrome. The curative efficacy of
      amtiinfective treatmatnt was poor, After treatment with HLH-2004 regimen, the
      fever symptome and the laboratory indicaters such as whole blood cells, ferritin
      and fibrinogen all were recovered to normal levels. Left mandibular
      lymphadenctasis was confirmed as Hodgkin's lymphoma (mixed cell type) by
      pathological examination. The patient achieved complete molecular remission after
      1 course chemotherapy with ABVD regimen. The level of EBV-DNA copy number were
      also decreased. As the reshlt, the patient's hemophagocytic syndrome had bean
      effectively controlled, and the Hodgkin's lymphoma is still in complete
      remission. CONCLUSION: Epstein-Barr virus-ratated hemophagocytic syndrome and
      Hodgkin's lymphoma are rare, and their long-term prognosis needs to be further
      explored.

PMID- 30111412
TI  - [Effect of IKK2 Inhibitor LY2409881 on Diffuse Large B-Cell Lymphoma Cell
      Apoptosis and Its Mechanism].
AB  - OBJECTIVE: To investigate the effects and its potential mechanism of IKK2
      inhibitor LY2409881 on proliferation, cell cycle and apoptosis of diffuse large B
      cell lymphoma (DLBCL) cell lines. METHODS: CCK8 assay was used to detect the
      effect of LY2409881 on proliferation of DLBCL cell lines; Flow cytometry was used
      to analyze cell cycle; Western blot was used to analyze apoptosis and its
      potential mechanism. RESULTS: LY2409881 inhibited the proliferation of multiple
      DLBCL cell lines obviously, and caused G1 cell arrest. Furtherly, LY2409881
      inhibited the expression of c-FLIP, induced the activation of DR4 and caspase 8.
      Meanwhile, LY2409881 induced the expression of pro-apoptotic protein BAX and
      inhibited the expression of anti-apoptotic protein MCL-1 and BCL-2. CONCLUSION:
      LY2409881 inhibits the proliferation of DLBCL cell lines, causes G1 cell arrest
      and induces apoptosis via the endogenous and exogenous apoptotic pathways.

PMID- 30111411
TI  - [Prognostic Value of Morphology and Hans Classification in Diffuse Large B Cell
      Lymphoma].
AB  - OBJECTIVE: To investigate the prognostic value of morphology and Hans
      classification in diffuse large B cell lymphoma(DLBCL). METHODS: Clinical data of
      249 patients diagnosed with DLBCL in our hospital and Hangzhou Xixi hospital
      during Jan 2006 to Dec 2016 were analyzed retrospectively. These patients were
      classified into 3 groups: immunoblastic variant(IB) group, centroblastic
      variant(CB) group and others group according to the cell morphology. And DLBCL
      was also divided into GCB(germinal center B-cell-like)or non-GCB(non-germinal
      center B-cell-like) group by analyzing the expression of CD10, BCL6 and MUM1
      (GCB: CD10 +,BCL6+-,MUM1+-/CD10-,BCL6+,MUM1-;non-GCB:CD10-,BCL6-,MUM1+-/CD10
      ,BCL6+,MUM1+). RESULTS: The univariate analysis displayed that the age,LDH
      level,IPI,IB,non-GCB,B-symptoms and rituximab all could influence the OS and EFS,
      the CR rate of CB subtype patients was significantly higher than that of the
      patients with IB subtype (68.3% vs 38.9%)(P=0.02). IB subtype was the in
      dependent prognostic factor for both EFS and OS in the whole study. In
      multivariate analysis, IPI and IB were the independent prognostic factors for OS
      and EFS. IB subtype was also an independent prognostic factor in EFS and OS with
      or without rituximab. The expression of BCL2 and BCL6 was related with prognosis
      in R-CHOP, but not in CHOP treated patients. Other markers (CD5, CD10, IRF4/MUM1,
      HLA-DR and Ki-67 proliferation index) were not of the significant prognostic
      value for DLBCL. When accepted rituximab, the GCB and non-GCB were not different
      significantly for prognosis. However, the non-GCB group showed a poor prognosis
      without using rituximab (EFS P=0.020;OS P=0.020). Multivariate Cox models showed
      that OS and EFS were not significantly different between GCB and non-GCB group,
      however, the IB subtype had a very significantly poor prognosis in OS and EFS
      (P=0.001, P=0.002). When the analysis was restricted to DLBCL with CB morphology
      only, no prognostic value was observed in Hans classification. CONCLUSION: The
      subtype of immunoblast is a major risk factor in patients treated with CHOP or R
      CHOP. There is a significant association between the Hans classification and the
      morphologic subclassification. Results of this study have supplemented the data
      for the prognostic factor of DLBCL and demonstrated that the cytomorphologic
      diagnosis can be reproducible.

PMID- 30111413
TI  - [Apoptosis of Murine T-Cell Lymphoma EL4 Cells Induced by Murine Cytomegalovirus
      and Its Mechanism].
AB  - OBJECTIVE: To detect whether the murine T-cell lymphoma cell line EL4 could be
      infected by murine cytomegalovirus (MCMV), and to observe the morphological
      changes and apoptosis of El4 cells before and after infection. METHODS: EL4 cells
      were infected with MCMV smith strain with 1, 10 and 100 multiplicity of infection
      (MOI) respectively. The morphology of the cells was observed by light microscopy
      and Wright's-Giemsa staining. The survival rate was calculated by trypan blue
      staining. RT-PCR-based assay was used to detect the copy number of MCMV-DNA in
      the infected ELA cells. Flow cytometry was used to detect apoptosis. RT-qPCR was
      used to detect the mRNA expression levels of P53, P21, cFlip and Caspase 8. The
      protein expression levels of Caspase8, P53, BAX, BCL-2 and Cleaved Caspase3
      proteins were detected by Western blot. RESULTS: After Wright-Giemsa staining, it
      was found that the infected EL4 cells displayed larger volume, irregular nuclei
      and the folded twist under light microscopy. Compared with the normal control
      group, the survival rate of EL4 cells decreased, and the apoptosis rate
      statistically significantly (P<0.05) increased with the increasing MOI and the
      infected time in each group. While, the level of apoptosis protein P53, BAX/BCL
      2, Cleaved-caspase3 and Caspase8 were up-regulated. And the survival rate,
      apoptosis rate and the apoptosis protein level of infected EL4 cells with MOI=10
      were the most obvious at the 5thday. Compared with MCMV infection group (MOI=60),
      the content of MCMV DNA in EL4 cells was decreased in MCMV+GGV group [MOI=60, GCV
      25 (g/ml)], and the cell apoptosis rate and apoptosis protein expression of P53,
      Caspase8, BAX/BCL-2 were decreased (P<0.05). CONCLUSION: Murine T-cell lymphoma
      cell line EL4 can be infected by MCMV and displayes an obvious apoptosis
      phenomenon. MCMV may up-regulate the expression levels of apoptosis protein P53,
      BAX-BCL-2, Cleaved-caspase3 and Caspase8 in EL4 cells. The drug ganciclovir
      reduces the copy mumber of MCMV DNA in infected EL4 cells and inhibited the
      killing effect of MCMV on EL4 cells.

PMID- 30111414
TI  - [Comparison of Clinical Characteristics, Curative Efficacy, Total Survival Rate
      and Progression -Free Survival Rate in Different Subtypes of Early Nasopharyngeal
      NK/T Cell Lymphoma].
AB  - OBJECTIVE: To compare the clinical characteristics, clinical efficacy, overall
      survival rate and progression-free survival rate between different subtypes of
      early nasopharyngeal NK/T cell lymphoma. METHODS: The clinical data of 83
      patients with early nasopharyngeal NK/T cell lymphoma in our hospital were
      retrospectively analyzed, the 83 patients were divided into 2 group: 59 cases of
      NK cell lymphoma as group A, 24 cases of cytotoxic T-cell phenotype as group B.
      The differences of clinical characteristics, clinical efficacy and survival
      prognosis were compared between the 2 groups. RESULTS: The incidence rate of
      lesion and bone destruction in the group A was significantly lower than those in
      the group B (P<0.05). The total effective rate in the group A was (91.53%)
      significantly higher than that in group B (58.33%) (P<0.05), and overall survival
      rate (59.32%) and progression-free survival rate (45.76%) of 5 years in the group
      A were significantly higher than those in the group B (29.17%, 16.67%) (Log
      rank=4.22, 4.41, P<0.05). Hemophagocytic syndrome was a risk factor for overall
      survival in patients with nasopharyngeal NK/T cell lymphoma (OR=3.03, 95%CI:1.53
      6.00, P<0.01), and sex, tumor subtype and involvement of lymph node were the
      related factors affecting progression-free survival (OR=2.01, 1.12, 3.68, 95%
      CI:1.07~3.77,1.05-1.19, 1.63-8.27, P<0.05). CONCLUSION: In the patients with
      early nasopharyngeal NK/T cell lymphoma, T cell lymphoma as compared with NK cell
      lymphoma is more prone to local invasion with poor clinical efficacy, survival
      and prognosis, therefore, chemotherapy methods should be actively adopted to
      improve prognosis of patients in clinic.

PMID- 30111415
TI  - [mRNA and Protein Expression of AXIN,beta-Catenin, MMP7 and MMP9 and Their
      Relationship in Lymphoma Cells].
AB  - OBJECTIVE: To investigate the mRNA and protein expression of axin inhibitor
      (AXIN), beta-chain protein (beta-catenin), matrix metalloproteinase-7 (MMP-7) and
      matrix metalloproteinase-9 (MMP-9), and their relationship in lymphoma cells.
      METHODS: The expressions of MMP-7, MMP-9, beta-catenin and AXIN in lymphoma cell
      lines were detected by Western blot and RT-PCR. Moreover, the lymphoma cells with
      relatively low expression of AXIN were grouped and were transiently transfected
      by using pcDNA5-His-beta-catenin and pCMV5-HA-AXIN; the protein and mRNA
      expression of MMP-7, MMP-9 and beta-catenin in lymphoma cells was detected by
      Western blot and RT-PCR, respectively; the cell infiltration and migration
      ability in group with stable ligh expression of AXIN, group of interfering stable
      high expression of AXIN and blank control group were analyzed by transwell
      experiment. RESULTS: The AXIN negatively correlated with MMP-7, MMP-9 and beta
      catenin expression in lymphoma cell lines. After the up-regulation of AXIN, the
      mRNA expression of MMP7, MMP-9 and beta-catenin in Raji cells all not
      significantly changed, while the pratein expression of MMP-7, MMP-9 and beta
      catenin all significantly decreased (P<0.05); after the up-regulation of beta
      catenin, the mRNA and protein expression of MMP-7, MMP-9 was also up-regulated
      significantly (P<0.05). After interfering the AXIN, the mRNA expression of MMP-7,
      MMP-9 and beta-catenin in group with stable high expression of AXIN all not
      changed significantly, while protein expression of MMP-7, MMP-9 and beta-catenin
      was down-regulated significantly (P<0.05); after interfering the beta-catenin,
      the protein and mRNA expression of MMP-7 and MMP-9 in group with stable high
      expression of AXIN all were down-regulated significantly(P<0.05). CONCLUSION: The
      up-regulation of AXIN expression in lymphoma cells can lead to decrease of beta
      catenin expression and the resuts in significant decrease of MMP-7 and MMP-9
      expression, there by plays a role to block the infiltration and migration of
      lymphoma cells.

PMID- 30111416
TI  - [Expression and Function of miR-181b in Diffuse Large B Cell Lymphoma].
AB  - OBJECTIVE: To investigate the expression and function of miR-181b in diffuse
      large B cell lymphoma (DLBCL). METHODS: The lymphoid tissues of 124 patients with
      DLBCL examined and treated in our hospital from March 2010 to March 2012 were
      used as the DLBCL group. The healthy lympaid dissases in another 64 patients with
      non lymphaoma were selected as the control group. The expression levels of miR
      181b in two groups were detected, and the expression levels of miR-181b in
      lymphoid tissues of DLBCL patients with different clinical features were
      compared. The survival of DLBCL patients with different levels of miR-181b
      expression was compared. RESULTS: The relative expression level of miR-181b in
      lymph tissues of DLBCL patients was significantly higher than that in healthy
      lymphoid tissues (P<0.05). The higher the Ann Arbor staging was, the higher the
      relative expression of miR-181b was in lymphoid tissues (P<0.05), and the higher
      the IPI score was, the higher the relative expression of miR-181b was in lymphoid
      tissues (P<0.05). The 5-year survival rate of the patients with miR-181b low
      expression was significantly higher than that of patients with miR-181b high
      expression (P<0.05). CONCLUSION: There are differences in the expression of miR
      181b in lymphoid tissues of DLBCL patients with different clinical stages and
      prognosis. It may become an effective indicator for the diagnosis and prognosis
      evaluation of DLBCL.

PMID- 30111417
TI  - [Effects of HDAC Inhibitor Scriptaid on IM9 Cell Line and Its Mechanism].
AB  - OBJECTIVE: To study the effect of HDAC inhibitor Scriptaid on multiple myeloma
      IM9 cells and preliminarily clarify the mechanism of Scriptaid-induced cell
      apoptosis. METHODS: The cell viability, cell cycle and cell apoptosis were
      measured by CCK8 assay and flow cytometry respectively, the relative target gene
      expression levels were detected by RT-PCR, the effect of Scriptaid on p21
      promoter activity was detected by using luciferase reporter assay. RESULTS:
      Scriptaid inhibited IM9 cell viability in a dose-dependent manner. Scriptaid
      induced IM9 cell cycle arrest at G2/M phase in a dose-dependent manner. Scriptaid
      triggered IM9 cell apoptosis was obviously, the mRNA levels of apoptosis-related
      proteins Caspase 9, Caspase 3 and PARP1 were also activated. The apoptosis
      associated factors BAD, PTEN and p21 increased following treatment with different
      dose of Scriptaid, meanwhile, p21 promoter activity was also activated
      significantly. CONCLUSION: HDAC inhibitor Scriptaid can promote IM9 cell
      apoptosis by transcriptional activation of p21 promoter in concentration
      dependent manner.

PMID- 30111418
TI  - [Detection and Diagnostic Values of JAK2, CALR, MPL Gene Mutations in 208 Cases
      of BCR/ABL1 Negative Chronic Myeloproliferative Diseases].
AB  - OBJECTIVE: To detect the JAK2, CALR and MPL gene mutations in patients with
      BCR/ABL1 negative chronic myeloproliferative diseases(BCR/ABL1-CMPD)and to
      evaluate their diagnostic value. METHODS: Two hundred and eight cases of BCR/ABL1
      CMPD comprising of 146 cases of essential thrombocythemia(ET), 37 cases of
      polycythemia vera(PV)and 25 cases of primary myelofibrosis(PMF)from March 2012 to
      December 2015 were enrolled in the BCR/ABL1-CMPD, while 124 cases of secondary
      thrombocythemia and 73 cases of secondary polycythemia were enrolled in the
      control group. The genomic DNA and total RNA Were isolated from bone marrow or
      peripheral blood, then the exons 12 to 20 of JAK2 gene, exon 10 of MPL gene and
      exons 3 to 9 of CALR gene were analyzed by using DNA sequencing. RESULTS: among
      146 ET patients, the JAK2, CALR or MPL mutations were found in: 138
      cases(94.5%)including 86 cases with JAK2V617F mutation(58.9%)and 2
      cases(1.4%)with exon 12 of JAK2 mutations. CALR mutations were detected in 41
      cases(28.1%), among them type 1(c.1092_1143del)in 22 cases, type
      2(c.1154_1155insTTGTC)in 11 cases, and type 5(c. 1091_1142del), type
      8(c.1104_1137del), type 41(c.1107_1137del), type 42(c.1125_1125del)in one case
      respectively. In addition, 4 cases were detected withother mutations of the CALR
      gene(c.1107_1115del, c.1111_1144 del, c.1101 A>C, c.1112_1117del). Moreover, 9
      cases harbored MPL mutations(6.2%). Secondly, 31 patients were detected with
      JAK2V617F mutation(83.8%)in 37 cases of PV, and JAK2 exon 12 mutations were found
      in 2 cases(5.4%). Besides, CALR mutations were detected in 2 cases(5.4%),
      including 1 case of type I, the other of novel mutation of CALR. Thirdly, 19 in
      25 cases of PMF were detected with JAK2V617F mutation(76%), 2 cases with CALR
      mutations(8%). 4 patients(16%), JAK2, CALR or MPL mutations were not detected,
      but among them 3 cases were found harboring other genetic abnormalities.
      Fourthly, no mutations of JAK2, MPL and CALR genes were detected in 124 patients
      with secondary thrombocytosis and 73 cases with secondary polycythemia.
      CONCLUSION: Combined detection of JAK2, CALR and MPL gene mutations can cover the
      vast majority of patients with BCR/ABL1-negative myeloproliferative neoplasms.
      For higher frequencies of the mutations of CALR in ET patients, CALR mutation can
      be used as a new diagnostic marker in ET patients with JAK2 and MPL wild type.

PMID- 30111419
TI  - [Establishment and Identification of MDS Mouse Model with Irom Overload].
AB  - OBJECTIVE: To establish a MDS mouse model with iron overload and to study the
      effect of iron overload on MDS. METHODS: The exogenous mutant gene RUNX1-S291fs
      was inserted into the mice bone marrow mononuclear cell's genome in mice by
      retrovirus and transplanted into C57BL/6 mice irradiated by 60 Co gamma-ray.
      After 8 weeks,intraperitoneal injection of iron was performed to establish an MDS
      mouse model with iron overload. After 24 weeks of transplantation, the peripheral
      blood, bone marrow, femur, liver and spleen of mice were taken, then the
      morphological characteristics of peripheral blood and bone marrow cells were
      observed by Wright's staining; the liver, spleen and bone marrow were stained
      with Prussian blue to observe the iron deposition. The surface antigens of bone
      marrow cells were detected by flow cytometry. Bone marrow mononuclear cells and
      spleen tissue proteins were detected by Western blot to confirm the transfection
      of RUNX1-S291fs gene and expression of protein. The blood routine and
      transplanted cell chimeric rate of mice were monitored periodically. RESULTS:
      Compared with the empty plasmid control mice, levels of leukocyte and hemoglobin
      as well as platelet were decreased in RUNX1-S291fs mutant mice; the peripheral
      blood cells and bone marrow cells showed pathological hematopoiesis; the liver
      and spleen enlarged significantly; the tissue structure of femur, liver and
      spleen was abnormal; the expression of bone marrow cell surface antigens was
      abnormal. Bone marrow cells and spleen tissue expressed the RUNX1-S291fs protein.
      Compared with the controlled mice injected with normal saline, iron deposition
      occurred in the bone marrow, liver and spleen stained with Prussian blue in the
      mice injected with iron agent. CONCLUSION: Mice engineered to carry exogenous
      mutant gene RUNX1-S291fs and injected with iron showed pathologic features of MDS
      and iron overload, resulting in establishing MDS iron overloaded mouse model
      successfully, which lays a foundation for studying the effect of iron overload on
      MDS.

PMID- 30111421
TI  - [Genotype Analysis of Patients with Thalassemia in Sanya Area of Hainan Province
      in China].
AB  - OBJECTIVE: To explore the frequency and spectrum of thalassemia gene mutations of
      the population in Sanya area of Hainan province in China. METHODS: The type and
      frequency of gene mutation in 1060 patients with suspected thalassemia were
      analyzed by Gap-PCR and reverse dot blot (RDB). RESULTS: The detection on
      mutation of thalassemia gene were found in 539 suspected thalassemia patients,
      the total detected rate was 50.85% (539/1060), out of them 330 (31.13%) were
      diagnosed with alpha-thalassemia, 162 (15.28%) with beta-thalassemia, and 47
      (4.43%) as carriers of both alpha and beta-thalassemia. In alpha-thalassemia
      patients, genotype were as follows in proper order--SEA/alphaalpha (9.25%),-alpha
      4.2/alphaalpha (5.94%),HbH (5.56%),-alpha 3.7/alphaalpha (5.00%),-alpha 3.7/
      alpha 4.2 (2.36%),-alpha 4.2/-alpha 4.2 (1.70%), and -alpha3.7/-alpha3.7(1.32%).
      In beta-thalassemia patients, there were 9 gene mutations: CD41-42 (9.8%), CD17
      (1.32%), 654 (1.23%), CD71-72 (1.23%), IVS-II-654 (1.04%), -28 (0.37%), CD43
      (0.19%), -29 (0.18%) and betaE (0.09%). In the alpha and beta composite
      thalassemia there were 12 genotypes. The -alpha3.7/alphaalpha was the most common
      genotype co-existed with beta-thalassemia (1.70%), followed by the -alpha 4.2
      /alphaalpha genotype (0.94%). CONCLUSION: The data of this study provide the
      frequency and the spectrum of thalassemia gene mutations in the sanya area of
      Hainan province, which can contribute to set up the strategies for the prevention
      and control of thalassemia in this area.

PMID- 30111420
TI  - [Clinical Characteristic of "triple-negative" Essential Thrombocythaemia Patients
      and Mutation Analysis by Targeted Sequencing].
AB  - BACKGROUND: Essential thrombocythemia is a subgroup of myeloproliferative
      neoplasms. Previous studies identified mutations of JAK2, CALR, and MPL that are
      closely related with the pathogenesis of myeloproliferative neoplasms. All these
      mutations contribute to the hyperactivation of JAK2/STAT pathway. However, a
      small proportion of essential thrombocythemia patients does not display such
      mutations. The pathogenesis of "triple-negative" form of essential
      thrombocythemia remains unknown. OBJECTIVE: To investigate the clinical
      characteristics of triple-negative essential thrombocythemia and related mutation
      genes. METHODS: To identify the mutations associated with triple-negative
      essential thrombocythemia, next-generation sequencing was used to conduct
      targeted sequencing of 360 genes in samples from 68 patients. RESULTS: At least
      one missense mutation was detected in all the patients and all the detected
      genes. After screening the data, it was observed that 10 genes with the 10
      highest mutation were follows: FLT3, SH2B3, ASXL1, ADAMTS1, TET2, TP53, EGFR,
      CUX1, GATA2, and MPL.When only rare genes (i.e., with a frequency in Asian
      populations lower than 5%, as estimated by the 1000 Genomes Project) were
      analyzed, the most frequently mutated genes in the patients were TET2 (33.82%),
      SH2B3(29.41%), and ASXL1 (23.53%). Our study identified some mutations that did
      not previously reported. Although all these mutations need further validation,
      high incidence rates may indicate relevance of the respective mutations to
      essential thrombocythemia pathogenesis. Some of the detected mutations have been
      previously reported; these mutations were also found in a large proportion of our
      subjects. CONCLUSION: whole-exon sequencing can provide a higher level of
      accuracy for gene mutation analysis and assist in identifying mutations that
      contribute to illustrate the pathogenesis of essential thrombocythemia.

PMID- 30111423
TI  - [Changes of Brain Proton Magnetic Resonance Spectroscopy Study in Hemorrhagic
      Shock: An Experimental Study on a Rabbit Model].
AB  - OBJECTIVE: To investigate the changes of cerebral metabolism in rabbit model of
      hemorrhagic shock by using proton magnetic resonance spectroscopy(PMRS). METHODS:
      Ten New Zealand white rabbits were used for construction of the model of acute
      hemorrhagic anemia. 1H-MRS was performed before and at the time-peint of 30, 90,
      and 180 min after hemorrhagic shock. The concentrations of NAA, Cr, Cho, Lac, and
      NAA/Cr and Cho/Cr ratios were estimated. RESULTS: Hemorrhagic shock was
      associated with significant reductions in red blood cell count, hemoglobin level,
      hematocrit, pH, and PaCO2, and elevations of blood lactate and PaO2. The ratios
      of NAA/Cr at 30 min, 90 min and 180 min after shock were (1.50+/-0.09), (1.37+/
      0.09) and (1.27+/-0.10), respectively, which were significantly lower than those
      before shock (2.11+/-0.16) (P <0.05) (1.16+/-0.05) and (0.97+/-0.04) at 30 min
      and 90 min after shock, respectively, which were significantly lower than those
      pre-shock (1.38+/-0.08) (P <0.05). The ratis of Cho/Cr at 30 min and 90 min were
      (1.16+/-0.05) and (0.97+/-0.04), respectively, which were significantly lower
      than those before shock (1.38+/-0.08) (P <0.05). CONCLUSION: MRS can
      noninvasively and dynamically detect brean metabolic changes in early hemorrhagic
      shock, and has positive significance for early diagnosis and prognosis assessment
      of hemorrhagic shock.

PMID- 30111422
TI  - [Number and Function of Myeloid-Derived Suppressor Cells in Patients with Adult
      Primary Immune Thrombocytopenia].
AB  - OBJECTIVE: To analyze the number of myeloid-derived suppressor cells(MDSC) and
      the level of prostaglandin E2(PGE2) in the bone marrow of adult ITP patients, and
      to explore their possible mechanisms involved in the pathogenesis of this
      disease. METHODS: Twenty-five patients of newly diagnosed ITP, 25 patients of
      complete remission group and 15 patients of control group were selected. The
      number of MDSC in the bone marrow between 3 groups was detect by flow cytometry
      (FCM). The serum level of prostaglandin E2 (PGE2) in 3 groups was determined by
      enzyme linked immunosorbent assay (ELISA). The relative expression of IFN-gamma
      mRNA in bone marrow mononuclear cells was measured by real time fluorescence
      quantitative polymerase chain reaction (RT-qPCR) in each groups. RESULTS: The
      number of MDSC in the complete remission group was significantly higher than that
      in the control group (P<0.05); the number of MDSC in the newly diagnosed group
      was higher than that in the control group; the number of MDSC in the complete
      remission group was higher than that in the newly diagnosed group. The serum
      level of PGE2 in bone marrow of ITP patients in the newly diagnosed group was
      higher than that of the control group(P<0.05). The serum level of PGE2 in the
      bone marrow of ITP patients of the complete remission group was higher than that
      of the control group (P<0.05). The level of PGE2 in bone marrow serum of ITP
      patients of the newly diagnosed group was lower than that in the complete
      remission group(P<0.05). The relative expression level of IFN-gamma in bone
      marrow mononuclear cells of the ITP patients in newly diagnosed group was higher
      than that in the control group and the complete remission group(P<0.001). The
      relative quantification (RQ) of IFN-gamma in bone marrow mononuclear cells was
      2.60 between the newly diagnosed group and the complete remission group.
      CONCLUSION: When adult ITP disease is remitted, the number of MDSC rises and
      correlates with the therapeutic response and PGE2 level in the bone marrow.

PMID- 30111424
TI  - [Expression of COX-1 and COX-2 in the Platelet of Iron Deficiency Anemia Women at
      Childbearing Age and Its Clinical Significance].
AB  - OBJECTIVE: To detect the expression level of cyclooxygenase-1(COX-1) and
      cyclooxygenase-2(COX-2) in the platelet of iron deficiency anemia(IDA)women at
      childbearing age and to explore its correlation with the different indexes of
      anemia and platelets. METHODS: Forty female IDA patients at childbearing age and
      35 healthy controls were enrolled in this study. The Flow cytometry was used to
      detect the expression of platelet COX-1 and COX-2,the platelet aggregation
      function as examined by turbidimetric method,and the levels of serum ferritin
      were analyzed by electrochemical luminescence method,the leval of serum iron was
      determined by ELISA,and the correlation of different indexes was analyzed.
      RESULTS: Compared with healthy controls,the levels of platelet COX-1 and COX-2
      were significantly lower in female IDA patients at Childbearing age(P<0.05),but
      platelet count(Plt),mean platelet volume(MPV) and platelet aggregation
      rate(PAgT)were not statistically different between the 2 groups(P > 0.05). The
      expression level of platelet COX-1 positively correlated with those of Hb(r
      =0.623,P<0.01),serum iron(r =0.321,P<0.05) and HCT(r=0.305,P<0.05). but the
      platelet COX-2 expression did not corelate with these indexs. CONCLUSION: The
      expression of platelet COX-1 and COX-2 in female IDA patients at Childbearing age
      markedly decrease,and the expression level of platelet COX-1 closely relates with
      the severity of anemia,that possesses reference value for clinical diagnosis of
      female IDA patients at Childbearing age..

PMID- 30111425
TI  - [Etiological Study of Late Onset Hemorrhagic Cystitis after Allogeneic
      Hematopoietic Stem Cell Transplantation in Children].
AB  - OBJECTIVE: To prospectively study the correlation BKV with the occurrence and
      development of late onset hemorrhagic cystitis (LOHC) after allogeneic
      hematopoietic stem cell transplantation(allo-HSCT). METHODS: The clinical data of
      a total of 276 patients with allo-HSCT in our department between January 1998 and
      March 2016 were analyzed ratrospectvely. Quantitative Real-time PCR assay was
      used to prospectively monitor the BKV DNA load of the urine and plasma for 23
      patients accepting allo-HSCT from August 2015 to March 2016. RESULTS:
      LOHC(24.28%) occurred in 67 of 276 cases with allo-HSCT. Univariate analysis
      showed that age older than 6 years, different diseases, unrelated donor,
      pretreatment with BU, III-IV aGVHD significantly correlated with LOHC.
      Multivariate analysis demonstrated that age older than 6 years (P<0.01),
      pretreatment with BU(P<0.05), and aGVHD of grade III-IV (P= 0.011) were the
      independent risk factors for LOHC. Among 23 patients after allo-HSTC, 10 of which
      were positive of urine BKV, and LOHC occurred in 6 cases. The positive rate of
      urine BKV (85.7%)in group LOHC+ was significantly higher than that in the group
      LOHC-(25.0%)(chi2=5.043, P<0.01). The incidence of LOHC positively correlated
      with the positive rate of BKV (r=0.564, P<0.01), and the severity of LOHC
      positively correlated with urinary BKV load (r = 0.502, P<0.01). And 5 of 6
      petriatic patients with LOHC had aGVHD. All of them were subject to the
      strengthened antiviral treatment, and 4 of them accepted intensive
      immunosuppression therapy. CONCLUSION: Age >=6 years old, precenditioning regieme
      with BU and aGVHD of grade III-IV are independent risk factors for LOHC after
      allo-HSCT, the positive rate of urine BKV load positively correlates with the
      severity of LOHC after allo-HSCT.

PMID- 30111426
TI  - [Risk Factors and Prognosis of Hepatic cGVHD after Allogeneic Hematopoietic Stem
      Cell Transplantation].
AB  - OBJECTIVE: To analyze the risk factors and prognosis of hepatic chronic GVHD
      after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS:
      The clinical data of 147 patients undergoing allo-HSCT from January 2013 to
      December 2016 were analyzed, the correlation between recipient age and sex,
      disease state, matched degree of HLA, donor sex, stem cell sources, ATG in GVHD
      prophylaxis, liver dysfunction during conditioning period, pre-transplant HBsAg,
      prior aGVHD and hepatic cGVHD were studied, and the correlation between hepatic
      cGVHD and prognosis were analysed. RESULTS: Thirty-two patients had hepatic
      cGVHD, cumulative incidence of 26.4%. In univariate analysis, pre-transplant
      HBsAg+and liver dysfunction during conditioning period were not significantly
      related with hepatic cGVHD (P>0.05). In multivariate analysis, prior acute GVHD
      (HR=2.087, P=0.045) was the independent risk factor for hepatic cGVHD, ATG
      (HR=0.231, P=0.000) was significantly related with a lower incidence of hepatic
      cGVHD. In univariate analysis, patients with hepatic cGVHD had a lower 2 years
      relapse rate (P=0.038). CONCLUSION: Prior acute GVHD is the independent risk
      factor for hepatic cGVHD, the ATG can significantly reduce the incidence of
      hepatic cGVHD. Hepatic cGVHD has been found to relate with a lower 2 years
      relapse rate.

PMID- 30111427
TI  - [Establishment of Trace Amount Bone Marrow Hematopoietic Stem Cells of Adult
      Mouse Transplantation System].
AB  - OBJECTIVE: To establish a transplantation system for a trace amount of adult
      mouse bone marrow hematopoietic stem cells (HSCs). METHODS: The HSCs from bone
      marrow cells of GFP adult mouse were seperated by using marker combination ESLAM
      (CD45+CD201+CD150+CD48-) The goal cell population acquired by flow cytometry
      sorting were injected into lethally irradiated recipient mouse plus protective
      cells. And the peripheral blood cells from recipient mice tail veins at different
      time points were acquired to observe the reconstruction level and lineage
      differentiation. Then the receptor mouse was killed and the cells from thymus,
      spleen, marrow, and peripheral blood were acquired to measure tissue chimerism.
      RESULTS: The results of peripheral blood of recipient mice after transplantation
      showed that the reconstructive efficiency was 100% after 4th week. The proportion
      of GFP+ cells at different time points in various lines (myeloid, erythroid, B, T
      and megakaryocytes) were different and the change tendency of reconstruction were
      different. From different tissues (peripheral blood, bone marrow, spleen, thymus)
      after 6 months, the intramedullary spleen and thymus chimerism can be seen and
      showed a high proportion of GFP+cells in the peripheral blood erythroid and
      megakaryocytes and there were no GFP+cells in the myeloid and lymphatic cells,
      but the myeloid cells in the bone marrow cells of the recipient mice contained a
      higher proportion of GFP+cells. The B cells in the spleen had a higher proportion
      of GFP+ cells, and the T cells in the thymus contained a higher proportion of
      GFP+ cells. CONCLUSION: The ESLAM combination can be highly efficient one for the
      enrichment of HSCs with long-term reconstructive ability, and the results of
      peripheral blood 6 months after the transplantation suggests that it may have the
      inclination to erythroid and megakaryocyte differentiation.

PMID- 30111429
TI  - [Hypobaric Hypoxia Induces Autophagy of Umbilical Cord Mesenchymal Stem Cells].
AB  - OBJECTIVE: To investigate the autophagy activity changes of umbilical cord
      mesenchymal cells (MSC) under hypobaric hypoxia and the effect of hypobaric
      hypoxia on cell viability. METHODS: Umbilical cord mesenchymal cells were
      cultured in the chamber of hypobaric hypoxia with an air pressure of 41.1 kPa and
      an oxygen density of 1%. At 0, 4, 8, 16, 24 and 48 hours, the cells were
      harvested for Western blot and real-time PCR to observe the expression level of
      the autophagy marker protein LC3B. And the cell viability under hypobaric hypoxia
      was evaluated after treatment with autophagy inhibitors HCQ (8 MUg/ml) and 3MA (5
      mmol/L). RESULTS: LC3B expression in MSC at protein and mRNA levels were up
      regulated significantly after being cultured under hypobaric hypoxia condition
      for 8 hours. And compared with the control group, inhibition of autophagy reduced
      cell viability while increased Caspase-3 expression and the incidence of
      apoptosis. CONCLUSION: Hypobaric hypoxia activates autophagy in MSC, and the
      activation of autophagy might play a protective role for cell survival.

PMID- 30111428
TI  - [Role of BET Bromodomain in Hematopoietic Differentiation from hESCs].
AB  - OBJECTIVE: To explore the role of bromodomain and extra terminal (BET)
      bromodomain in hematopoietic differentiation from human enbryonic stem cells
      (hESC). METHODS: The effect of BET hematopoietic inhibitor I-BET151 on
      hematopoietic differentiation from hESC was detected by using a monolayer
      hematopoietic defferentiation model, immunofluorescence, flow cytometry and real
      time PCR; moreover the role of I-BET151 in process of hematopoietic
      differentiation was explored by adding I-BET151 in different differentiation
      stages. RESULTS: The analysis results of immunofluorescence, flow cytometry and
      real-time PCR showed that I-BET 151 significantly inhibited the generation of
      CD43 positive hematopoietic stem and progenitor cells (HSPCs). It was found that
      the addition of I-BET 151 in different stages, including APLNR+ lateral plate
      mesoderm production, CD34+CD31+ hemogenic endothelium (HEP) generation and
      endothelial-to-hematopoietic transition, significantly suppressed the generation
      of CD43 positive hematopoietic progenitor cells. CONCLUSION: I-BET 151 inhibites
      hematopoietic differentiation from hESCs at several stages, suggesting that the
      BET bromodomain plays important roles in multiple stages of hematopoietic
      differentiation from hESCs.

PMID- 30111430
TI  - [Detection of HHV-8 Virus in 450 Free Blood Donons in Wuhan and Its Genotyping
      Based on ORFK1 Gene].
AB  - OBJECTIVE: To investigate the infection of HHV-8 virus in free blood donors in
      Wuhan. METHODS: Whole blood samples were collected from 450 free blood donors in
      Wuhan, and the genomic DNA extraction and serum collection were performed
      respectively. And then, the positive rate of HHV-8 was detected by PCR and ELISA,
      the positive detection rates were compared between them. Finally, HHV-8 ORFK1
      gene was cloned by PCR in the positive samples, and the HHV-8 ORFK1 gene th was
      genetyped through sequencing analysis, homology comparison and phylogenetic tree
      construction. RESULTS: 25 and 23 cases of positive samples were detected by PCR
      and ELISA, their positive rate were 5.56% and 5.11% respectively, and without
      statistically significant difference using chi2 test analysis (P > 0.05). Based
      on the results of ORFK1 gene cloning and sequence analysis in 23 positive
      samples, 15 samples C subtype of had HHV-8 ORFK1 gene, and 8 cases had A subtype
      had HHV-8 ORFK1 gene. CONCLUSION: There is a certain percentage of HHV-8
      infection in the free blood donors in Wuhan. It is suggested to increase the HHV
      8 virus screening for free blood donors, so as to ensure the quality of blood.

PMID- 30111431
TI  - [Analysis of Relationship between Coagulation Function and Blood Transfusion in
      Patients with Emergency Rescue].
AB  - OBJECTIVE: Through researching preoperative coagulation function in the case of
      ABO-identical blood insufficient for emergency rescue transfusion according to
      recommended programs of special emergency rescue transfusion was carried out, the
      relationship between volume of blood products and coagulation function was
      analyzed. METHODS: The surgical cases of blood transfusion more than 1 600 ml
      during operation were collected in our hospitals from Aug 2015 to Dec
      2016(n=218), these cases were divided into the normal coagulation group(Group A)
      and abnormal coagulation group(Group B), and the patients of emergency rescue
      transfusion O type blood group(Group C). The basic information of cases, the
      infused volume of red blood cell(RBC), virus-inactivated frozen plasma(VIFP),
      fresh frozen plasma(FFP), cryoprecipitate(C)and platelets(P), prothrombin
      time(PT), activated partial thromboplastin time(APTT), fibrinogen(FIB)and
      international normalized ratio(INR)were analyzed, the relationship between volume
      of blood transfusion and coagulation function were also analysed. At the same
      time, the efficiency and safety index were compared before and after transfusion.
      These indexes, such as hemoglobin(Hb), indirect bilirubin(IBiL), direct
      antiglobulin test(DAT)and irregular antibody were determined at the time-paints
      of 24 h, 3 d and 7 d after blood transfusion. RESULTS: The differences of age and
      blood type between group A and B was not statistically significant(P>0.05).
      Proportion of A and AB type,transfusion volume of RBC, FFP, C and Plt all were
      significantly higher in group C (P<0.05). PT, APTT, FIB and INR in group B and C
      were significantly different(P<0.05), which related with the transfusion volume
      of RBC, FFP and C(P<0.05). DAT and irregular antibody in every group was all
      negative before transfusion, No any new irregular antibodies had been detected
      after transfusion. Hb after blood transfusion was not statistically different
      before and after transfusion in group C, the IBiL level also was not
      significantly increased after blood transfusion(P > 0.05). All those showed that
      emergency rescue transfusion was safe and effective. CONCLUSION: Preoperative
      coagulation function is one of factors inflnencing blood products transfusion
      volume during operation, which also is the basis for evaluating bleeding and
      blood transfusion. Emergency O type blood and ABO-matched blood transfusions show
      the same efficiency and safety.

PMID- 30111432
TI  - [Diagnostic Value of Combined Detection of HLA-G and IL-6 in Children with
      Infectious Mononucleosis].
AB  - OBJECTIVE: To investigate the diagnostic value of combined detection of HLA-G and
      IL-6 in children with infectious mononucleosis (IM). METHODS: Eighty-three
      children suffered from infectious mononucleosis hospitalized in Wuhan Children's
      Hospital(Wuhan Maternal and Child Healthcare Hospital) from January 2014 to June
      2017 were selected as the IM group, 83 healthy children in the same period were
      selected as the as control group. Enzyme-linked in munosorbent assay (ELISA) was
      used to detect and compare the changes of HLA-G and IL-6 levels between 2 groups.
      The positive rate of HLA-G and IL-6 were calculated and compared. The correlation
      of plasma HLA-G with IL-6 in IM group was analyzed, the MOC curve was drawn, and
      the diagnostic efficiencies of plasma HLA-G and IL-60 alone as well as 2 combined
      detection were compared. RESULTS: The plasma level of HLA-G and IL-6 in IM group
      was significantly higher than that in control group, and the difference between
      the 2 groups was were statistically significant (P<0.01). In untreated children
      with infectious mononucleosis, the positive rate of plasma HLA-G detection was
      90.36% (75/83) and the positive rate of IL-6 detection was 87.95% (73/83) without
      a significant difference between 2 groups (P>0.05). There was a positive
      correlation between the plasma HLA-G and IL-6 levels in the observation group
      (r=0.196, (P<0.05). The analysis of ROC curve diagnostic effectiveness showed
      that the diagnostic sensitivity of IL-6 was 68.90%, the specificity was 71.50%,
      and the area under the ROC curve was 0.703. The diagnostic sensitivity of the
      plasma HLA-G was 74.20%, the specificity was 77.50%, and the area under the ROC
      curve was 0.761. The combined diagnostic sensitivity and specificity of 2 methods
      was 89.50% and 85.70% respectively, and the area under the ROC curve was 0.906.
      CONCLUSION: The combination of HLA-G and IL-6 for detect infectious mononucleosis
      resulted in a high sensitivity and accuracy, which is helpful to define the
      progress of the patient's condition, and worth for clinical application.

PMID- 30111433
TI  - [Advances of studies on Purification and Tracking of Hematopoietic Stem Cells
      Using Their Specific Gene Expression--Review].
AB  - Hematopoietic stem cells (HSC) maintain homeostatic hematopoiesis via their multi
      lineage differentiation and self-renewal potentials. HSC can be enriched and
      purified by flow cytometry relying on their cell surface markers and functional
      characteristics, however, these methods can not meet the need for deep analysis
      of HSC biological property and function because of the poor purity. Recent
      studies have successfully purified and tracked HSC using specifically expressed
      genes, which can enhance the purification efficiency of HSC, thus provide a
      better tool for the in-vivo study of HSC. This review summarizes the new
      techniques and discusses their advantages and disadvantages.

PMID- 30111434
TI  - [Research Progress on Diagnosis and Treatment of B Cell Chronic
      Lymphoproliferative Disease--Review].
AB  - The 2016 world health organization (WHO) classification of B cell chronic
      lymphoproliferative disease (B-CLPD) includes chronic lymphocytic leukemia (CLL),
      B prolymphocytic leukemia, (B-PLL), hairy cell leukemia (HCL), marginal zone
      lymphoma (MZL), follicular lymphoma (FL), mantle cell lymphoma (MCL), Waldenstrom
      macroglobulinemia (LPL/WM). All the above-mentioned diseases are partially
      similar in cell morphology, immunophenotype and molecular genetics, but
      significantly different in treatment and prognosis. Currently, many new drugs
      targeted at cell cycle and apoptosis pathway, such as proteasome inhibitor immune
      modulators and histone deacetylase inhibitors, have achieved encouraging results
      in B-CLPD, which bring new hope for patients with B-CLPD. The review will discuss
      the progress in diagnosis and treatment of B-CLPD in recent years.

PMID- 30111435
TI  - [Progress in Treatment of POEMS Syndrome--Review].
AB  - POEMS syndrome is a rare multiple organ involvement of the parasympathetic
      syndrome associated with abnormal plasma cells, mostly with high-dose
      chemotherapy and stem cell transplantation for the treatment. Recently, more
      treatment attempts to treat POEMS syndrome have been utilized so as to improve
      the efficacy and safety for the patients with POEMS syndrome, such as
      immunomodulator, alkylating agent, cytokine-induced killer cells and so on.
      Lenalidomide has a significant effect on relapse/refractory POEMS syndrome and
      patients with endocrinopathy. Cytokine-induced killer cells are also a safe and
      effective regimen for the treatment of POEMS syndrome. This review described the
      efficacy and safety of immunomodulatos, alkylators, cytokine-induced killer
      cells, ASCT, proteasome inhibitors and monoclonal antibodies for POEMS syndrome,
      and the newest clinical research and progress of POEMS syndrome ware summarized
      briefly.

PMID- 30111436
TI  - [Research Advances of Acquired Thrombotic Thrombocytopenic Purpura--Review].
AB  - Thrombotic thrombocytopenic purpura (TTP) is an acute, potentially life
      threatening thrombotic microangiopathies (TMA). TTP has mainly been diagnosed by
      clinical findings, such as thrombocytopenia and microangiopathic haemolytic
      anemia. In addition, the reduced activity of von Willebrand factor-cleaving
      metalloproteinase ADAMTS13 below 10% has been accepted internationally as a
      diagnostic criterion for TTP. In clinic, the accurate diagnosis and early
      initiation of therapy can significantly improve the survival rate of patients.
      Therapy should be focused on increasing ADAMTS13 activity and eliminating or
      inhibiting ADAMTS13 antibody by the infusion or exchange of therapeutic plasma
      and corticosteroids. Both the administration of recombinant ADAMTS13 and reducing
      the release of human neutrophil peptides (HNPs) would be novel promising
      strategies for the prevention of platelet-vWFinteraction. This review briefly
      summarizes the recent advances in terms of pathogenesis, diagnosis and treatment
      of TTP.

PMID- 30111437
TI  - [Research Progress on Dendritic Cells Combined with Cytokine Induced Killer Cells
      Immunotherapy for Hematological Malignancies --Review].
AB  - In recent years, with the incidence of malignant tumors increasing year by year,
      its treatment has been made great progress on the basis of traditional treatments
      such as surgery, radiotherapy and chemotherapy, it mainly focuses on rapid
      development of cellular immunotherapy. The efficacy of dendritic cells combined
      with cytokine induced killer cell (DC-CIK) immunotherapy for cancer patients is
      positive, it shows good antitumor activities and the abilities to reconstruct and
      enhance the immune system of tumor patients in clinical application, it has
      potential application value. In the treatment of hematologic malignancies which
      are chemotherapy-based and high-grade malignant, what is the effect of DC-CIK
      cells immunotherapy for them? In this review, we searched Chinese and abroad
      literatures from 2012 to 2018 and further focused on 18 clinical research
      articles about hematologic malignancies in order to analyze the characteristics
      of DC-CIK cells immunotherapy. It was found that DC-CIK cells can be an effective
      and promising treatment for patients with hematologic malignancies, and thus, if
      the process and unified plan are further standardized and improved, the efficacy
      will be more obvious. For this purpose, this paper reviews the biological
      characteristic of DC cells, CIK cells and the clinical research progress of DC
      CIK cell immunotherapy for hematological malignancies.

PMID- 30111438
TI  - [Molecular Mechanism of CRBN in the Activity of Lenalidomid eagainst Myeloma-
      Review].
AB  - Cereblon(CRBN) is a brain-associated protein with ionic protease activity, which
      interacts with DNA damage-binding protein-1 (DDB1), Cullin 4 (Cul4A or Cul4B),
      and regulator of Cullins 1 (RoC1) to form the functional E3 ubiquitin ligase
      complex(CRBN-CRL4) that performs proteolysis via the ubiquitin-proteasome
      pathway. And CRBN is a necessary target protein for the anti-myeloma effect of
      immunomodulators. The combination of lenalidomide and CRBN recruited a new
      substrate that binds to the CRBN-CRL4 complex, leading to increased
      ubiquitination and proteasome-dependent degradation, thus resulting in anti
      myeloma activity. The substrates binding to this complex are IKZF1, IKZF3
      proteins and GS, etc. The CRBN-dependent degradation of IKZF1 and IKZF3 after
      lenalidomide treatment is also the result of H2O2-mediated oxidative stress. In
      addition to ubiquitination, lenalidomide also mediates ubiquitin-independent
      pathways that prevent CRBN from binding to CD147-MCT1 in a competitive manner to
      regulate its antitumor activity. Lenalidomide can also play a role in multiple
      myeloma(MM) cells by modulating miRNA levels and CRBN binding to downstream
      protein AGO2 expression. Thus, there are many molecular mechanisms of
      lenalidomide anti-myeloma activity. This review summarizes the molecular
      mechanisms of CRBN in lenalidomide against myeloma activity in terms of ubiquitin
      dependent and ubiquitin-independent pathways.

PMID- 30111439
TI  - [Progress of Clinical Application of SNP-A to MDS--Review].
AB  - Cytogenetic abnormalities get wide attention for its guidance value for prognosis
      and therapy in myelodysplastic syndrome (MDS) and related malignancies.
      Cytogenetic analysis is also the key to clarify the molecular pathogenesis of
      these kinds of diseases. The traditional karyotyping technique including
      metaphase cytogenetic (MC) karyotype analysis and immune fluorescence in situ
      hybridization (FISH) can detect the chromosomal abnormalities to some degree
      while the positive rate detected by the techniques is low due to the low
      resolution, dependence on metaphase dividing cells or the limitation of specific
      sites on the chromosomes, respectively. Although array comparative genomic
      hybridization (aCGH) makes up for some deficiencies of the techniques above, only
      copy number variations (CNVs) could be detected by aCGH. Recently, single
      nucleotide polymorphasim array (SNP-A) are employed to detect chromosomal CNVs
      and uniparental disomies (UPDs) which are significant for illumination of the
      pathogenetics and prognosis of MDS. Based on the detection principle and
      characteristics of SNP-A, this article reviews the clinical application and
      prospect of the technique in aspect of the detection characteristic of SNP-A, the
      relationship between cryptic aberrations and MDS related aspects including the
      pathogenic genes, phenotypes, prognosis, stratification system and self control
      test.

PMID- 30111440
TI  - [Research Advances of Molecular Genetic Abnormality in Myelodysplastic Syndrome-
      Review].
AB  - The myelodysplastic syndromes (MDS) are a heterogeneous group of clonal myeloid
      disorders characterized by ineffective hematopoiesis and increased risk of
      transformation to acute myelogenous leukemia (AML). The treatment of MDS is
      highly dependent on the reliability of the prognostic evaluation model. Current
      clinical prognostic scoring systems are comprised of morphology, pivotal clinical
      trials and cytogenetic findings. However, none of the available prognostic
      systems incorporates disease-related molecular abnormalities, such as somatic
      mutations. Cumulative evidence suggests that genomic data can also be used
      clinically to assist the diagnosis, prognosis, prediction of response to specific
      therapies, and the development of novel and accurate targeted therapies.
      Therefore, it is not possible to predict the response of patients to molecular
      targeted drugs, such as demethylation drugs. With the recent advance in whole-
      genome sequencing technologies, cumulative evidence suggests that genomic data
      can also be associated with the genesis, prognosis, prediction of response to
      specific therapies, and the development of novel accuvate targeted therapies, the
      issue of having some mechanism to dissect this heterogeneity and precision
      treatment is coming to the fore. However, there are still several hindrances to
      its clinical application. If these problems can be solved, molecular genetics
      will further provide a theoretical basis for the application of precision
      medicine in MDS.

PMID- 30111441
TI  - [Advances of Targeting Therapy in Acute Myeloid Leukemia--Review].
AB  - Although the application of combined chemotherapy has made a great progress in
      treatment of adult acute myeloid leukemia (AML), the overall survival rate is
      still not high, mainly because of high recurrence rate and drug resistance. The
      treatment regimen for relapsed/refractory AML is always strong. Due to the
      chemotherapy drugs lacking of specific identification of tumor cells, significant
      adverse reactions often come out and sometimes even endanger the life of
      patients. In order to improve the life quality and survival rate, the new
      treatment strategy is urgently needed. With the deepening of research, the new
      molecular targets of tumor cells including the abnormal expression of cell
      surface morecules, gene mutation and abnormal gene methylation has been found.
      Targeted drugs for these abnormal changes could improve the prognosis of AML
      patients, providing a new way for AML treatment. This review summarizas the
      progress of molecular targeted therapy of AML.

PMID- 30111442
TI  - Physician-diagnosed eczema is an independent risk factor for incident mouse skin
      test sensitization in adults.
AB  - BACKGROUND: The disrupted skin barrier in eczema has been associated with an
      increased risk of immunoglobulin E (IgE) sensitization in childhood. However, it
      is unclear whether eczema, independent of atopy, is a risk factor for the
      development of allergic sensitization in adulthood. OBJECTIVE: To determine if
      skin barrier dysfunction, independent of atopy, is a risk factor for incident
      sensitization in adult workers at a mouse production and research facility.
      METHODS: New employees at The Jackson Laboratory enrolled in a cohort study and
      underwent skin-prick testing (SPT) at baseline and every 6 months to mouse and to
      a panel of aeroallergens (net wheal >=3 mm indicated a positive SPT result).
      Mouse allergen exposure was measured every 6 months by using personal air
      monitors. Physician-diagnosed eczema was defined as self-reported physician
      diagnosed eczema. Cox proportional hazard modeling was used to examine the
      association between baseline physician-diagnosed eczema and incident mouse skin
      test sensitization and adjusted for potential confounders. RESULTS: The
      participants (N = 394) were followed up for a median of 24 months. Fifty-four
      percent were women, 89% were white, and 64% handled mice. At baseline, 7% of the
      participants reported physician-diagnosed eczema and 9% reported current asthma;
      61% had at least one positive skin test result. At 30 months, 36% of those with
      eczema versus 14% of those without eczema had developed a positive mouse skin
      test result (p = 0.02, log-rank test). After adjusting for age, race, sex,
      smoking status (current, former, never), current asthma, hay fever, the number of
      positive SPT results at baseline, and mouse allergen exposure, physician
      diagnosed eczema was an independent risk factor for incident mouse SPT
      sensitization (hazard ratio 5.6 [95% confidence interval, 2.1-15.2]; p = 0.001).
      CONCLUSION: Among adult workers at a mouse production and research facility,
      physician-diagnosed eczema was a risk factor for incident mouse sensitization,
      independent of atopy, which indicated that a defect in skin barrier alone may
      increase the risk of skin sensitization, not just in childhood, but throughout
      life.

PMID- 30111466
TI  - [Comparison of clinical efficacy of two noninvasive respiratory support therapies
      for respiratory distress syndrome in very low birth weight preterm infants].
AB  - OBJECTIVE: To compare the clinical efficacy of nasal intermittent positive
      pressure ventilation (NIPPV) and heated humidified high flow nasal cannula
      (HHHFNC) in the treatment of respiratory distress syndrome (RDS) among very low
      birth weight (VLBW) preterm infants. METHODS: A total of 89 very low birth weight
      premature infants with respiratory distress syndrome (RDS) who were randomly
      administered with NIPPV (n=46) and HHHFNC (n=43) as an initial respiratory
      support. The incidence of initial treatment failure, the usage of pulmonary
      surfactant (PS), the parameters of respiratory support treatment and the
      incidence of complications were compared between the two groups. RESULTS: There
      were no significant differences between the NIPPV and HHHFNC groups in the
      following items: the rate of intubation within 72 hours, rate of PS use, duration
      of invasive or non-invasive mechanical ventilation, duration of oxygen therapy,
      and incidence rates of severe apnea and pneumonia (P>0.05). There were also no
      significant differences in the incidence rates of bronchopulmonary dysplasia,
      necrotizing enterocolitis, retinopathy of prematurity, patent ductus arteriosus,
      intracranial hemorrhage, and air leak between the two group (P>0.05). The
      incidence rate of nose injury in the NIPPV group was higher than that in the
      HHHFNC group (P<0.05). CONCLUSIONS: As an initial respiratory support for very
      low birth weight preterm infants with RDS, HHHFNC has a similar clinical effect
      as NIPPV, suggesting that HHHFNC is a safe and effective clinical option as a non
      invasive ventilation treatment.

PMID- 30111467
TI  - [Effect of prone positioning on respiratory function in very preterm infants
      undergoing mechanical ventilation].
AB  - OBJECTIVE: To explore the effect of prone positioning on respiratory function in
      very preterm infants undergoing mechanical ventilation. METHODS: A total of 83
      very preterm infants treated with mechanical ventilation were enrolled in the
      study and were randomly assigned to supine group and prone group. Four infants
      withdrew from the study and 79 infants completed treatment and observation (37 in
      the supine group and 42 in the prone group). Infants in both groups were
      mechanically ventilated in a volume assist-control mode. Infants in the prone
      group were ventilated in the supine position for 4 hours and in the prone
      position for 2 hours. Ventilator parameters, arterial blood gas analysis, and
      vital signs were recorded before grouping, every 6 hours in the supine group, and
      every hour after conversion into the prone position in the prone group,
      respectively. RESULTS: Fraction of inspired oxygen (FiO2), peak inspiratory
      pressure, mean inspiratory pressure, and duration of ventilation were
      significantly lower in the prone group than in the supine group (P<0.05); there
      were no significant differences in tidal volume or positive end-expiratory
      pressure between the two groups (P>0.05). The prone group had a significantly
      higher PO2/FiO2 ratio but significantly lower oxygenation index and respiratory
      rate than the supine group (P<0.05). There were no significant differences in
      arterial oxygen tension, pH, base excess, heart rate, or mean blood pressure
      between the two groups (P>0.05). CONCLUSIONS: Alternating ventilation between the
      prone position and supine position can improve oxygenation function, decrease the
      fraction of inspired oxygen, and shorten the duration of mechanical ventilation
      in very preterm infants undergoing mechanical ventilation.

PMID- 30111468
TI  - [Effect of golden-hour body temperature bundle management on admission
      temperature and clinical outcome in preterm infants after birth].
AB  - OBJECTIVE: To study the effect of golden-hour body temperature bundle management
      strategy on admission temperature and clinical outcome in preterm infants with a
      gestational age of <34 weeks after birth. METHODS: The preterm infants who were
      born in the delivery room of the West China Second University Hospital of Sichuan
      University and admitted to the department of neonatology of this hospital within
      1 hour after birth from December 2015 to June 2016 and from January to May, 2017
      were enrolled. The 173 preterm infants who were admitted from January to May,
      2017 were enrolled as the intervention group and were given golden-hour body
      temperature bundle management. The 164 preterm infants who were admitted from
      December 2015 to June 2016 were enrolled as the control group and were given
      conventional body temperature management. RESULTS: The intervention group had a
      significantly higher mean admission temperature than the control group (36.4+/
      0.4 degrees C vs 35.3+/-0.6 degrees C; P<0.001). The incidence rate of
      hypothermia on admission in the intervention group was significantly lower than
      that in the control group (56.6% vs 97.6%; P<0.001). The intervention group had a
      significantly lower incidence rate of intracranial hemorrhage within one week
      after admission than the control group (15.0% vs 31.7%; P<0.05). CONCLUSIONS:
      Golden-hour body temperature bundle management for preterm infants within one
      hour after birth can reduce the incidence of hypothermia on admission and improve
      clinical outcome.

PMID- 30111469
TI  - [Effect of intrauterine growth retardation on insulin sensitivity and plasma
      adiponectin level in neonates].
AB  - OBJECTIVE: To explore the effect of intrauterine growth retardation (IUGR) on
      insulin sensitivity in neonates and the relationship between insulin sensitivity
      and plasma adiponectin level. METHODS: Eighty-two term neonates with IUGR and 90
      term neonates born appropriate for gestational age (AGA) were enrolled. Weight,
      height, head circumference and abdomen circumference of the neonates were
      measured within 24 hours after birth. Fasting serum glucose (FG), triglyceride
      (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), plasma
      insulin and adiponectin were detected in two groups on the 7th day after birth.
      Homeostasis model assessment for insulin resistance (HOMA-IR) index and insulin
      sensitivity index (ISI) were calculated. RESULTS: There were no significant
      differences in the levels of FG, TG, HDL and LDL between the IUGR and AGA groups
      (P>0.05). The plasma insulin level in the IUGR group was higher than that in the
      AGA group, but the plasma adiponectin level was lower than that in the AGA group
      (P<0.05). HOMA-IR index in the IUGR group was higher than that in the AGA group,
      but ISI was lower than that in the AGA group (P<0.05). Both Pearson correlation
      analysis and multiple linear regression analysis showed HOMA-IR index was
      negatively correlated with plasma adiponectin level and birth weight (P<0.05).
      CONCLUSIONS: The neonates with IUGR display a higher plasma insulin level and
      decreased insulin sensitivity. The decreased plasma adiponectin level may be
      associated with the decreased insulin sensitivity.

PMID- 30111470
TI  - [Diagnostic value of endogenous morphine in childhood sepsis].
AB  - OBJECTIVE: To investigate the plasma concentration of endogenous morphine and the
      value of endogenous morphine in predicting shock, death, and multiple organ
      dysfunction syndrome (MODS) in children with sepsis. METHODS: A total of 31
      children with sepsis who met the diagnostic criteria were enrolled. According to
      the presence or absence of shock, they were divided into non-shock group with 19
      children and shock group with 12 children. According to the outcome, they were
      divided into survival group with 22 children and death group with 9 children.
      According to the presence or absence of MODS, they were divided into non-MODS
      group with 13 children and MODS group with 18 children. In addition, 16 children
      with common infection and 31 who underwent physical examination were enrolled as
      controls. High-performance liquid chromatography-mass spectrometry was used to
      measure the plasma concentration of endogenous morphine. The receiver operating
      characteristic (ROC) curve was used to evaluate the value of endogenous morphine
      in predicting shock, death, and MODS in children with sepsis. RESULTS: No
      endogenous morphine was detected in the healthy control group. Endogenous
      morphine was detected in 3 children from the common infection group and in all of
      31 children with sepsis. The shock group had a significantly higher plasma
      concentration of endogenous morphine than the non-shock group (P<0.05). The death
      group had a significantly higher plasma concentration of endogenous morphine than
      the survival group (P<0.05). The MODS group had a significantly higher plasma
      concentration of endogenous morphine than the non-MODS group (P<0.05). The ROC
      curve showed that endogenous morphine had certain value in predicting shock,
      death, and MODS in children with sepsis (P<0.05). CONCLUSIONS: There is a
      significant increase in the plasma concentration of endogenous morphine in
      children with sepsis, and endogenous morphine has a good value in predicting the
      risk of shock, death, and MODS.

PMID- 30111471
TI  - [Clinical features and treatment of macrolide-resistant Mycoplasma pneumoniae
      pneumonia in children].
AB  - OBJECTIVE: To study the clinical features of macrolide-resistant Mycoplasma
      pneumoniae pneumonia and its treatment regimens in children. METHODS: The samples
      of throat swab or bronchoalveolar lavage fluid were collected from 136 children
      with Mycoplasma pneumoniae pneumonia. Quantitative real-time PCR was used to
      detect 2063/2064 A:G mutation in 23S rRNA, and according to such results, the
      children were divided into drug-resistance group with 81 children and sensitive
      group with 55 children. The two groups were compared in terms of age composition,
      respiratory symptoms, extrapulmonary complications, laboratory markers, imaging
      changes, treatment regimens, and length of hospital stay. RESULTS: Compared with
      the sensitive group, the drug-resistance group had significantly longer duration
      of pyrexia and severe fever, a significantly higher percentage of children with
      reduced blood oxygen saturation, and significantly higher levels of alanine
      aminotransferase (ALT) and lactate dehydrogenase (LDH) (P<0.05). The conventional
      azithromycin treatment had a good clinical effect in the sensitive group, while
      corticosteroid therapy was usually needed in the drug-resistance group.
      CONCLUSIONS: Macrolide-resistant Mycoplasma pneumoniae infection cannot be
      identified based on a single clinical feature, but prolonged duration of pyrexia
      and severe fever, reduced blood oxygen saturation, and increased ALT and LDH can
      suggest the presence of this disease. Azithromycin combined with glucocorticoids
      may be a good treatment regimen for children with macrolide-resistant Mycoplasma
      pneumoniae pneumonia.

PMID- 30111472
TI  - [Effects of L-carnitine on serum levels of brain natriuretic peptide and N
      terminal pro-brain natriuretic peptide and cardiac function in children with
      severe hand-foot-mouth disease].
AB  - OBJECTIVE: To observe the effects of L-carnitine treatment on serum levels of
      brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) and cardiac
      function in children with heart dysfunction and severe hand-foot-mouth disease
      (HFMD). METHODS: A total of 120 children with severe HFMD were enrolled and
      randomly and equally divided into routine treatment group and L-carnitine
      treatment group. Thirty healthy children served as the control group. HFMD
      patients were given anti-fever and antiviral treatment as the basic treatment,
      while the patients in the L-carnitine treatment group were given L-carnitine as
      an adjuvant treatment to the basic treatment. Treatment outcomes were observed in
      the two groups. For all the subjects, serum levels of BNP and NT-proBNP and
      cardiac function parameters including left ventricular ejection fraction (LVEF),
      fractional shortening (FS), and cardiac index (CI) were measured at different
      time points before and after treatment. RESULTS: Before treatment, HFMD patients
      had significantly higher serum levels of BNP and NT-proBNP and heart rate but
      significantly lower LVEF, FS, and CI compared with the control group (P<0.05).
      After treatment, the L-carnitine treatment group had a significantly higher
      response rate than the routine treatment group (P<0.05). After 3 days of
      treatment, the serum levels of BNP and NT-proBNP, LVEF, FS, and CI were
      significantly reduced in the L-carnitine group (P<0.05); the L-carnitine group
      had significantly lower serum levels of BNP and NT-proBNP, LVEF, FS, and CI than
      the routine treatment group (P<0.05); there were no significant differences in
      the serum levels of BNP and NT-proBNP, LVEF, FS, or CI between the L-carnitine
      treatment and control groups (P>0.05). After 5 days of treatment, there were no
      significant differences in the serum levels of BNP and NT-proBNP, LVEF, FS, or CI
      between the L-carnitine treatment and routine treatment groups (P>0.05). Heart
      rate recovery was significantly slower in the routine treatment group than in the
      L-carnitine treatment group (P<0.05). CONCLUSIONS: As an adjuvant therapy for
      severe HFMD, L-carnitine treatment has satisfactory short-term efficacy in
      reducing the serum levels of BNP and NT-proBNP and improving cardiac function,
      thus improving clinical outcomes.

PMID- 30111473
TI  - [Association of FokI rs2228570 and TMPRSS6 rs855791 polymorphisms with cow's milk
      protein allergy in children].
AB  - OBJECTIVE: To study the association of polymorphisms of FokI rs2228570 in the
      vitamin D receptor (VDR) gene and TMPRSS6 rs855791 with cow's milk protein
      allergy (CMPA) in children. METHODS: Quantitative real-time PCR was used to
      analyze the single nucleotide polymorphisms of FokI rs2228570 in the VDR gene and
      TMPRSS6 rs855791 in 100 children with CMPA and 100 healthy children (control
      group). The multivariate logistic regression model was used to identify the risk
      factors for CMPA. RESULTS: There were significant differences in the frequencies
      of CC, CT, and TT genotypes of TMPRSS6 rs855791 between the CMPA and control
      groups (P=0.008), and the CMPA group had a significantly higher frequency of TT
      genotype. The multivariate logistic regression analysis showed that the children
      with TT genotype of rs855791 had an increased risk of CMPA (OR=3.473, P=0.011).
      However, there was no significant difference in the genotype distribution of FokI
      rs2228570 in the VDR gene between the two groups (P=0.686). CONCLUSIONS: TMPRSS6
      rs855791 polymorphism is associated with CMPA in children, and TT genotype may be
      the susceptible genotype of CMPA. FokI rs2228570 polymorphism is not associated
      with CMPA.

PMID- 30111474
TI  - [Diagnosis and treatment of 3-hydroxyisobutyryl-CoA hydrolase deficiency: a case
      report and literature review].
AB  - A case of 3-hydroxyisobutyryl-CoA hydrolase deficiency was reported, and its
      clinical features, gene mutation characteristics, and diagnosis and treatment
      were analyzed with reference to related literature. The patient aged 1 year and 6
      months had developmental regression and paroxysmal dystonia after pyrexia and
      diarrhea, and head MRI showed symmetrical lesions in the bilateral basal ganglia.
      No pathogenic mutation was found in the full-length detection of mitochondrial
      genome. Nuclear gene detection of mitochondrial-related diseases found new
      compound heterozygous mutations in the HIBCH gene, i.e., c.439-2A>G and c.958A>G
      (p.K320E), which were inherited from his father and mother, respectively. The boy
      was given cocktail therapy, dietary valine restriction, and symptomatic
      treatment. After 2 weeks of treatment, there were improvements in dystonia and
      motor and intellectual development.

PMID- 30111475
TI  - [A clinical and genetic analysis of a child with supernumerary marker chromosome
      15-caused mental retardation, intractable epilepsy, and central precocious
      puberty].
AB  - Supernumerary marker chromosome 15 is a rare chromosome abnormality. This paper
      reports the clinical diagnosis and treatment, as well as genetic defects, of a
      child with supernumerary marker chromosome 15. The patient was a 9.5-year-old
      girl who had mental and motor retardation since infancy, breast development at
      the age of 7 years, and seizures at the age of 8.5 years. Seizures occurred with
      various features and could not be controlled by a variety of antiepileptic drugs.
      No abnormalities were found by brain magnetic resonance imaging.
      Electroencephalogram showed frequent epileptiform discharges. G-banding karyotype
      analysis, fluorescence in situ hybridization, methylation-specific multiplex
      ligation-dependent probe amplification, and array comparative genomic
      hybridization identified a de novo 15q duplication in the patient. The maternal
      copy number increased in the 15q11-13 region. The form of genome rearrangement
      was 47,XX,+inv dup(15)(pter to q13:q13 to pter). The increased copy number in the
      15q11-13 region is closely related to mental retardation, intractable epilepsy,
      and central precocious puberty. High-resolution karyotype analysis is recommended
      for children with unexplained mental retardation and epilepsy.

PMID- 30111476
TI  - [Value of Pediatric Early Warning Score in identifying the condition of
      critically ill children].
AB  - OBJECTIVE: To study the value of Pediatric Early Warning Score (PEWS) in
      identifying the condition of critically ill children. METHODS: A total of 120
      children who were transferred to the pediatric intensive care unit (PICU) from
      the general ward during hospitalization or admitted to the PICU after emergency
      treatment in the Xiangya Hospital of Central South University from January to
      December, 2016 were enrolled as the PICU group. The other 120 children who were
      admitted to the general ward in the hospital were used as the control group.
      According to the disease type, the PICU group was further divided into two
      subgroups: respiratory/circulatory system diseases (n=55) and nervous/other
      system diseases (n=65). The PEWS score on admission was recorded, and the
      receiver operating characteristic (ROC) curve was used to analyze the value of
      PEWS in evaluating patients' condition. RESULTS: The PICU group had a
      significantly higher PEWS score than the control group (P<0.05). The
      respiratory/circulatory system disease subgroup had a significantly higher PEWS
      score than the nervous/other system disease subgroup (P<0.05). In predicting
      whether the child was admitted to the PICU, PEWS had a sensitivity of 85%, a
      specificity of 95%, and an area under the ROC curve (AUC) of 0.951 (95%
      confidence interval: 0.923-0.980) at the optimal cut-off value of 3.5 (PEWS
      score). The AUC of PEWS was 0.768 in the nervous/other system disease subgroup
      and 0.968 in the respiratory/circulatory system disease subgroup. The mortality
      rate of children with a PEWS score of >6, 4-6 and <=3 was 40%, 21% and 0
      respectively (P<0.001). CONCLUSIONS: PEWS can well identify disease severity in
      critically ill children, and it has different sensitivities in children with
      different varieties of diseases. PEWS has a good value in predicting children's
      prognosis.

PMID- 30111477
TI  - [Developmental level of joint attention ability in children aged 16-30 months and
      related influencing factors].
AB  - OBJECTIVE: To investigate the developmental level of joint attention ability in
      children aged 16-30 months and factors influencing the developmental level.
      METHODS: A questionnaire survey was performed among 1 675 children aged 16-30
      months who visited the Department of Child Health Care in Guangdong Women and
      Children's Hospital between September and December, 2016 to investigate their
      joint attention ability and related influencing factors. RESULTS: Of the 1 675
      children, 1 579 (94.27%) had reactive joint attention ability at the age of 16-30
      months, and 1 428 (85.25%) had active joint attention ability. The percentages of
      children with reactive joint attention ability and active joint attention ability
      in boys were lower than in girls (P<0.001). Mother's age, father's occupation,
      annual family income, way of conception, intended or unintended pregnancy, and
      mode of delivery were factors influencing the total score of joint attention
      ability and the scores of reactive/active joint attention ability (P<0.05).
      CONCLUSIONS: Most children have reactive joint attention ability and active joint
      attention ability at the age of 16-30 months. During this period of age, boys
      tend to have poorer joint attention ability than girls. Mother's age, father's
      occupation, annual family income, way of conception, intended or unintended
      pregnancy, and mode of delivery are associated with the development of joint
      attention.

PMID- 30111478
TI  - [Current status of social anxiety and depression among primary school students in
      Urumqi, China].
AB  - OBJECTIVE: To investigate the current status of social anxiety and depression
      among the fourth-, fifth-, and sixth-grade students in Urumqi, China, and to
      provide data support for mental health education for primary school students in
      the future. METHODS: Stratified cluster random sampling was performed to select
      919 fourth-, fifth-, and sixth-grade students from four primary schools for the
      Han and minority ethnic groups in Urumqi as research subjects. Social Anxiety
      Scale for Children and Children's Depression Inventory were used to evaluate the
      current status of social anxiety and depression. RESULTS: Among the 919 fourth-,
      fifth-, and sixth-grade students, the detection rate of social anxiety was 28.5%
      (262 students). The fourth-grade students had significantly lower scores on each
      subscale of social anxiety and total score of social anxiety than the fifth- and
      sixth-grade students (P<0.05). Girls had significantly higher score on the
      subscale of fear of negative evaluation and total score of social anxiety than
      boys (P<0.05). The Uyghur students had significantly higher scores on each
      subscale of social anxiety and total score of social anxiety than the Han
      students and the students of other minority ethnic groups (P<0.05). Among these
      fourth-, fifth-, and sixth-grade students, the detection rate of depression was
      11.2% (103 students). The fourth-grade students had significantly lower scores on
      the subscales of negative self-esteem, ineffectiveness, and interpersonal
      problems and total score of depression than the fifth- and sixth-grade students
      (P<0.05). The Uyghur students had significantly higher scores on the subscales of
      anhedonia and negative mood and total score of depression than the Han students
      and the students of other minority ethnic groups (P<0.05). CONCLUSIONS: There are
      significant differences in the status of social anxiety and depression among the
      primary school students with different grades, sexes or ethnic groups in Urumqi.
      The fifth- and sixth-grade students, girls, and Uyghur students tend to have more
      serious psychological problems, which should be taken seriously by parents,
      schools, and the society.

PMID- 30111480
TI  - [A review of the relationship between gut microbiome and necrotizing
      enterocolitis in preterm infants].
AB  - Necrotizing enterocolitis (NEC) is a common severe gastrointestinal disease in
      preterm infants. The morbidity and mortality of NEC are negatively correlated
      with the gestational age and birth weight. In addition to causing a variety of
      gastrointestinal complications, NEC can also cause neurodevelopmental impairment.
      Recently, many studies have found that gut microbiome dysbiosis plays an
      important part in the pathogenesis of NEC. It is helpful to explore the
      relationship between gut microbiome and NEC for the early diagnosis and severity
      prediction of NEC. Researchers have paid much attention to the role of probiotics
      in reducing the morbidity and mortality of NEC in preterm infants. It's
      controversial as to whether probiotics is effective and safe in clinical
      application. This article will review the relationship between the development of
      gut microbiome and NEC in preterm infants, as well as the preventive effect of
      probiotics on NEC.

PMID- 30111479
TI  - [17alpha-Hydroxylase deficiency with severe hypertension as the initial symptom
      in a child].
AB  - A 14-year-old female (social gender) patient was admitted to the hospital due to
      severe hypertension for 11 days. The patient had primary amenorrhea. The blood
      pressure was 146/90 mm Hg. The skin color was slightly black. The development of
      secondary sexual characteristics was poor. The labia majora could be observed in
      the vulva. However, the labia minora, clitoris, vagina, and hymen were absent.
      The levels of renin, cortisol, and sex hormone were low, while the levels of
      adrenocorticotropic hormone and gonadotropin were high. The levels of blood
      potassium and aldosterone were both normal. Radiography indicated retardation of
      bone age. Ultrasound examination revealed that the ovary and uterus were both
      absent. The patient had bilateral adrenal hyperplasia and cryptorchid testes
      located in both inguinal canals. The patient had a 46,XY karyotype. Whole genome
      sequencing revealed two homozygous mutations, c.985T>C and c.987delC, in exon 6
      of the CYP17A1 gene of the patient and heterozygous mutations in the same sites
      of the parents. The patient was diagnosed with congenital adrenal hyperplasia
      17alpha-hydroxylase deficiency. After treatment with hydrocortisone for 2 months,
      blood pressure returned to normal and the level of adrenocorticotropic hormone
      was reduced. According to the request of the patient and the parents,
      hydrocortisone was replaced with estrogen to allow the patient to live as a
      female. The patient also received surgical excision of cryptorchid testes to
      prevent gonadal malignancy. It is concluded that in the differential diagnosis of
      pediatric hypertension, sexual development should be considered and the levels of
      adrenocorticotropic hormone and cortisol should be evaluated. The rare disease
      17alpha-hydroxylase deficiency should be considered for patients with low-renin
      hypertension and gonadal dysgenesis.

PMID- 30111481
TI  - [Application of the Evidence-based Practice for Improving Quality method in
      neonatal intensive care units].
AB  - The Evidence-based Practice for Improving Quality (EPIQ) method was proposed by
      Canadian Neonatal Network for high quality health care. The method is
      characterized by evidence-based, targeted, collaborative and continuous concept.
      At present it is applied in neonatal intensive care units (NICUs). This review
      article focuses on the application of the method in NICUs.

PMID- 30111482
TI  - [A review of gene therapy for Duchenne muscular dystrophy].
AB  - Duchenne muscular dystrophy (DMD) is an X-linked recessive hereditary disease
      caused by mutations in the DMD gene that encodes dystrophin. It is characterized
      by progressive muscle weakness and degeneration of skeletal muscle and myocardium
      due to the absence of dystrophin. The disease often occurs at the age of 2-5
      years, and most children may die of heart failure or respiratory insufficiency at
      the age of around 20 years. At present, supportive therapy is often used in
      clinical practice to improve symptoms, but this cannot improve the outcome of
      this disease. The development of gene therapy brings new hope to the cure of this
      disease. This article summarizes gene replacement therapy for DMD, including the
      research advances in DMD gene transduction technology mediated by adeno
      associated virus, utrophin protein upregulation technology, and clustered
      regularly interspaced short palindromic repeat gene editing technology, and
      reviews the recommendations to solve the issues of adeno-associated viral load,
      long-term effective expression of transgenic products, and utrophin protein
      expression, in order to provide a reference for further research.

PMID- 30111483
TI  - Associations between economic dependence, sexual behaviours, and sexually
      transmitted infections among young, Black, gay, bisexual and other men who have
      sex with men living with and without HIV in Jackson, Mississippi, USA.
AB  - Background: In the USA, young Black gay, bisexual or other men who have sex with
      men (YBMSM) bear the largest burden of HIV incidence. The aim of this study is to
      examine the independent associations between economic dependency on a sexual
      partner and several HIV risk behaviours and sexual health outcomes among YBMSM
      living in Jackson, Mississippi, USA. Methods: Baseline data from 589 YBMSM, with
      a median age of 22.0 years (IQR = 15-25) participating in a brief sex-positive
      HIV and STI prevention intervention, were used to measure the association between
      six sexual behaviours, sexually transmissible infections (STIs) status at
      baseline and economic dependence. Bivariate chi2 associations were tested and
      regression models adjusted for education level (<= high school), employment and
      HIV-status. Results: In regressions, of the six sexual behaviours reported in the
      last 90 days and six STIs tested at baseline, economically dependent YBMSM were
      more likely to report condomless anal receptive sex (aOR = 2.19, 95%CI = 1.25
      3.83), >=3 partners as a top (aOR = 1.99, 95%CI = 1.17-340), >=3 sex partners as
      a bottom (aOR = 2.07, 95%CI = 1.24-3.45), >=3 sex acts as a bottom (aOR = 2.10,
      95%CI = 1.16-3.82) and testing positive for oral gonorrhoea (aOR = 2.39, 95%CI =
      1.18-4.83) after controlling for HIV status, employment and education.
      Conclusions: Interventions should consider how poverty, unemployment and economic
      dependence interact to influence relationship power imbalances, condom use and
      sexual positioning agency, and sexual health for key populations of MSM.

PMID- 30111484
TI  - Framework for better care: reconciling approaches to patient safety and quality.
AB  - In September 2017, the Royal Australasian College of Medical Administrators
      adopted a new clinical governance framework that recognised healthcare as a
      complex adaptive system, and embraced the need for resilient thinking and
      understanding the differences between work-as-imagined by managers and work-as
      done at the front line of patient care. Directors of medical services may soon be
      implementing the framework in health services across Australia. This perspective
      describes a new conceptual model that underpins the Royal Australasian College of
      Medical Administrators framework, and characterises the challenges faced by all
      healthcare professionals when trying to achieve safe care for patients in an
      environment of variable complexity and unpredictability.

PMID- 30111485
TI  - 1st scientific symposium on Health and Climate Change, Italian National Institute
      of Health, 3-5th December 2018, Rome, Italy.

PMID- 30111486
TI  - Prognostic Implications of Point-of-Care and Serial B-type Natriuretic Peptide
      Levels in Patients With Hypertrophic Cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HC) is a heterogenous disease with a variable
      clinical course. Predictors of long-term adverse cardiovascular events are
      needed. Our objectives were to determine the long-term prognostic value of a
      single and serial point of care (POC) B-type natriuretic-peptide (BNP)
      measurements in HC. One hundred and eleven ambulatory patients with HC (mean age
      53 +/- 16 years) were prospectively recruited over a 2-year period (2004 to
      2006). A clinical assessment, comprehensive echocardiogram, and a POC BNP level
      was obtained at baseline and at a 1- to 2-year follow-up. They were subsequently
      followed for the occurrence of major adverse cardiac events (MACE). The median
      baseline BNP concentration was 114 pg/ml (range 5.3 to 1550 pg/ml). During a mean
      follow-up of 6.2 +/- 3.4 years, 42 patients (38%) had a MACE. In a multivariable
      Cox model including clinical and echocardiographic predictors, logBNP (HR 4.30;
      95% confidence interval 1.97 to 9.37, p <0.001) and left ventricualr ejection
      fraction (LVEF) (HR 0.96; 95% confidence interval 0.94 to 0.99, p = 0.011)
      remained significant predictors of MACE. Nested models demonstrated incremental
      prognostic value of logBNP for MACE (chi-square increased from 4.3 to 22.8, p
      <0.01) over clinical and echocardiographic factors. Patients with persistently
      elevated BNP (>100 pg/ml) at baseline and at the second visit were at a higher
      risk of developing MACE during follow-up (5-year MACE-free survival of 0.91 (SE
      0.06) vs 0.45 (SE 0.09), p <0.001). In conclusion, POC BNP levels in patients
      with HC were predictive of long-term MACE and had independent and incremental
      value. Patients with persistently elevated BNP levels were at a higher risk of
      MACE.

PMID- 30111487
TI  - Mitochondrial dysfunction in ATP13A2 carriers.

PMID- 30111488
TI  - Structural motifs in the RGS RZ subfamily combine to attenuate interactions with
      Galpha subunits.
AB  - Regulators of G-protein Signaling (RGS) proteins inactivate heterotrimeric G
      proteins, thereby setting the duration of active signaling. In particular, the
      RGS RZ subfamily, which consists of RGS17, RGS19, and RGS20, mediates numerous
      physiological functions and human pathologies - mostly by functioning as GTPase
      Activating Proteins (GAPs) towards the Galphai subfamily. Yet, which RZ subfamily
      members mediate particular functions and how their GAP activity and specificity
      are governed at the amino acid level is not well understood. Here, we show that
      all RZ subfamily members have similar and relatively low GAP activity towards
      Galphao. We characterized four RZ-specific structural motifs that mediate this
      low activity, and suggest they perturb optimal interactions with the Galpha
      subunit. Indeed, inserting these RZ-specific motifs into the representative high
      activity RGS16 impaired GAP activity in a non-additive manner. Our results
      provide residue-level insights into the specificity determinants of the RZ
      subfamily, and enable to study their interactions in signaling cascades by using
      redesigned mutants such as those presented in this work.

PMID- 30111489
TI  - The effect of plaque eccentricity on blood hemodynamics and drug release in a
      stented artery.
AB  - Atherosclerosis in the coronary arteries is one of the leading causes of death in
      the world. Percutaneous coronary interventions (PCI) associated with the
      implantation of drug eluting stents (DES) is one of the most common forms of
      revascularization in patients with atherosclerotic coronary artery disease. The
      use of DES is considered as an effective tool to reduce restenosis after PCI.
      However despite all the progress made in DES procedures, the rate of restenosis
      remains relatively high. Mathematical modeling and numerical simulation are
      believed to play an essential role in identifying zones with a higher risk of in
      stent restenosis. In this work the local delivery of a therapeutic agent, from a
      stent implanted in a coronary artery, is mathematically modeled and numerically
      simulated. The mathematical model includes the diffusion of the dissolved drug in
      the biodegradable polymeric coating of the stent, the diffusion and convection of
      the drug with reversible binding in the viscoelastic arterial wall with plaques
      of different morphology and the local hemodynamics. The study is an attempt to
      detect zones with a higher risk of in-stent restenosis and their relation to
      plaque eccentricity. The location of zones with highest risk of thrombosis and
      plaque rupture is also addressed. The results are in agreement with claims
      presented in clinical papers.

PMID- 30111490
TI  - HPV-related cancers-we can prevent them and we should.

PMID- 30111491
TI  - Structural Capacitance in Protein Evolution and Human Diseases.
AB  - Canonical mechanisms of protein evolution include the duplication and
      diversification of pre-existing folds through genetic alterations that include
      point mutations, insertions, deletions, and copy number amplifications, as well
      as post-translational modifications that modify processes such as folding
      efficiency and cellular localization. Following a survey of the human mutation
      database, we have identified an additional mechanism that we term "structural
      capacitance," which results in the de novo generation of microstructure in
      previously disordered regions. We suggest that the potential for structural
      capacitance confers select proteins with the capacity to evolve over rapid
      timescales, facilitating saltatory evolution as opposed to gradualistic canonical
      Darwinian mechanisms. Our results implicate the elements of protein
      microstructure generated by this distinct mechanism in the pathogenesis of a wide
      variety of human diseases. The benefits of rapidly furnishing the potential for
      evolutionary change conferred by structural capacitance are consequently
      counterbalanced by this accompanying risk. The phenomenon of structural
      capacitance has implications ranging from the ancestral diversification of
      protein folds to the engineering of synthetic proteins with enhanced
      evolvability.

PMID- 30111492
TI  - Peripartum cardiomyopathy-diagnosis, management, and long term implications.
AB  - Peripartum cardiomyopathy (PPCM) is a potentially life-threatening pregnancy
      associated disease that typically arises in the peripartum period. While the
      disease is relatively uncommon, its incidence is rising. It is a form of
      idiopathic dilated cardiomyopathy, defined as pregnancy-related left ventricular
      dysfunction, diagnosed either towards the end of pregnancy or in the months
      following delivery, in women without any other identifiable cause. The clinical
      presentation, diagnostic assessment and treatment usually mirror that of other
      forms of cardiomyopathy. Timing of delivery and management require a
      multidisciplinary approach and individualization. Subsequent pregnancies
      generally carry risk, but individualization is required depending on the pre
      pregnancy left ventricular function. Recovery occurs in most women on standard
      medical therapy for heart failure with reduced ejection fraction, more frequently
      than in other forms of nonischemic cardiomyopathy. The purpose of this review is
      to summarize the current state of knowledge with regard to diagnosis, treatment
      and management, with a focus on long term implications.

PMID- 30111493
TI  - Oral antioxidant therapy for prevention and treatment of preeclampsia: Meta
      analysis of randomized controlled trials.
AB  - AIMS: To determine whether oral antioxidant therapies, of various types and
      doses, are able to prevent or treat women with preeclampsia. DATA SYNTHESIS: The
      following databases were searched: MEDLINE, CENTRAL, LILACS, and Web of Science.
      Inclusion criteria were: a) randomized clinical trials; b) oral antioxidant
      supplementation; c) study in pregnant women; d) control group, treated or not
      with placebo. Papers were excluded if they evaluated antioxidant nutrient
      supplementation associated with other non-antioxidant therapies. Data were
      extracted and the risk of bias of each study was assessed. Heterogeneity was
      analyzed using the Cochran Q test, and I2 statistics and pre-specified
      sensitivity analyses were performed. Meta-analyses were conducted on prevention
      and treatment studies, separately. The primary outcome was the incidence of
      preeclampsia in prevention trials, and of perinatal death in treatment trials.
      Twenty-nine studies were included in the analysis, 19 for prevention and 10 for
      treatment. The antioxidants used in these studies were vitamins C and E,
      selenium, l-arginine, allicin, lycopene and coenzyme Q10, none of which showed
      beneficial effects on the prevention of preeclampsia (RR: 0.89, CI 95%: [0.79
      1.02], P = 0.09; I2 = 39%, P = 0.04) and other outcomes. The antioxidants used in
      the treatment studies were vitamins C and E, N-acetylcysteine, l-arginine, and
      resveratrol. A beneficial effect was found in intrauterine growth restriction.
      CONCLUSIONS: Antioxidant therapy had no effects in the prevention of preeclampsia
      but did show beneficial effects in intrauterine growth restriction, when used in
      the treatment of this condition.

PMID- 30111494
TI  - Longitudinal association between ideal cardiovascular health status and muscular
      fitness in adolescents: The LabMed Physical Activity Study.
AB  - BACKGROUND AND AIMS: Muscular fitness is an emerging predictor for cardiovascular
      disease mortality. The ideal cardiovascular health metrics has been inversely
      related to a subsequent cardiometabolic health in adulthood. However, evidence
      regarding muscular fitness and ideal cardiovascular health in adolescents is
      scarce. This study aimed to examine the longitudinal association between ideal
      cardiovascular health index and muscular fitness. METHODS AND RESULTS: This study
      cohort consisted of 331 adolescents (183 girls) from the LabMed Physical Activity
      Study who were followed from 2011 to 2013. Ideal cardiovascular health, as
      defined by the American Heart Association, was determined as meeting ideal health
      factors (total cholesterol, blood pressure, and glucose) and behaviors (smoking
      status, body mass index, physical activity, and diet). Handgrip strength and
      standing long jump tests assessed muscular fitness and were transformed into
      standardized values according to age and sex. ANCOVA showed a significant
      association between the accumulation of ideal cardiovascular health metrics at
      baseline and muscular fitness indices at follow-up (F(4, 322) = 2.280, p = 0.04).
      In addition, the higher the number of ideal cardiovascular health metrics
      accumulated, the higher the likelihood of having a high muscular fitness over a
      two-year period (p for trend = 0.01), after adjustments for age, sex, pubertal
      stage and socioeconomic status and muscular fitness at baseline. CONCLUSION: The
      ideal cardiovascular health status during adolescence was associated with high
      muscular fitness levels over a two-year period.

PMID- 30111495
TI  - Regular brief interruptions to sitting after a high-energy evening meal attenuate
      glycemic excursions in overweight/obese adults.
AB  - BACKGROUND AND AIMS: Modern Western lifestyles are characterized by consumption
      of approximately 45% of total daily energy intake at the evening meal, followed
      by prolonged sitting while watching television (TV), which may deleteriously
      impact glycemic control. After a high-energy evening meal (dinner), we examined
      whether regular, brief activity bouts during TV commercial breaks could acutely
      lower postprandial glucose and insulin responses in overweight/obese adults,
      compared to prolonged uninterrupted sitting. METHODS AND RESULTS: Nine
      overweight/obese adults (29.7 +/- 4.06 kg m-2; aged 32 +/- 3 years; 5 male)
      completed two laboratory-based conditions of three and a half hours: prolonged
      sitting during TV viewing (SIT); and, prolonged sitting interrupted every 20 min
      with 3 min of light-intensity body-weight resistance activities (active
      commercial breaks; ACBs). Venous postprandial glucose and insulin responses to
      dinner were calculated as positive incremental area under the curve (iAUC) from
      baseline. Interstitial glucose was measured using a continuous glucose monitor
      and quantified as total AUC (tAUC). Compared to SIT, plasma glucose iAUC was
      reduced by 33% [3.4 +/- 1.0 vs 5.1 +/- 1.0 (mean +/- SEM) mmol h.L-1, p = 0.019]
      and plasma insulin iAUC by 41% (813 +/- 224 vs 1373 +/- 224, p = 0.033 pmol h.L
      1) for the ACB condition. During the ACB condition there was a significant
      reduction in interstitial glucose tAUC (24.4 +/- 5.2 vs 26.9 +/- 5.2 mmol h.L-1,
      p < 0.001), but this did not persist beyond the laboratory observation period.
      CONCLUSIONS: Regular brief light-intensity activity bouts can attenuate glycemic
      responses during television viewing time following a high-energy evening meal in
      overweight/obese adults.

PMID- 30111496
TI  - Effects of preadipocytes derived from mice fed with high fat diet on the
      angiogenic potential of endothelial cells.
AB  - BACKGROUND AND AIMS: Obesity promotes a persistent inflammatory process in the
      adipose tissue, activating the endothelium and leading to vascular dysfunction.
      Preadipocytes can interact with endothelial cells in a paracrine way stimulating
      angiogenesis. However, the potential of preadipocytes from adipose tissue of high
      fat diet (HFD) fed animal to stimulate angiogenesis has not been evaluated yet.
      The aim of this study was to investigate the effects of such diet on the
      angiogenic potential of preadipocytes in a mice model. METHODS AND RESULTS: We
      have evaluated body weight gain, fasting glucose levels and insulin resistance,
      mRNA expression in preadipocytes and endothelial cells after co-culture with
      preadipocytes, in vivo vascular function and in vitro endothelial cell migration
      and tubulogenesis. High fat diet promoted an increase in body weight, glycemic
      index and insulin resistance in mice. Preadipocytes mRNA expression of factors
      involved in angiogenesis was higher in these animals. In endothelial tEnd cells
      mRNA expression of factors involved in vessel growth were higher after co-culture
      with preadipocytes derived from mice fed with HFD. Although no significant
      differences were observed in in vivo vasodilatation response between control and
      HFD groups, endothelial tEnd cells showed an increase in migration and
      tubulogenesis when cultivated with conditioned media from preadipocytes derived
      from mice fed with HFD. CONCLUSION: Hypoxic and growth factors produced by
      preadipocytes derived from mice fed with HFD have higher capacity than
      preadipocytes derived from mice fed with standard diet to stimulate the
      angiogenic potential of endothelial cells, contributing to vascular disorders in
      obesity.

PMID- 30111497
TI  - Evaluating Renal Fibrosis with R2* Histogram Analysis of the Whole Cortex in a
      Unilateral Ureteral Obstruction Model.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to use histogram analysis to
      assess the correlation between blood oxygen-level dependent magnetic resonance
      imaging (BOLD-MRI) and renal fibrosis induced by unilateral ureteral obstruction
      (UUO) in an animal model for a long experimental period. MATERIALS AND METHODS:
      The rabbits were randomly divided into a control group (n = 6) and a UUO group (n
      = 30). The rabbits in the UUO group underwent left ureteral obstruction surgery.
      BOLD-MRI examinations were performed at 2, 4, 6, and 8 weeks after ligation.
      After the examinations, nephrectomy was performed for histologic evaluation.
      Histogram analysis of the left renal cortex (C) R2* values was performed to
      measure the mean, median, 10th percentile, 90th percentile, skewness, and
      kurtosis for all kidneys. Masson trichrome staining was used to assess the
      percentage of fibrotic area. RESULTS: The histogram R2* values of the mean,
      median, 10th percentile, and 90th percentile at week 2 were all lower than those
      at baseline. Over the course of UUO progression, there were statistical
      differences between the histogram R2* values at any other two time points, except
      between weeks 4 and 6, and weeks 6 and 8. A close correlation was found between
      the percentage of fibrotic area and R2* values (mean: F = 21.49, p = 0.0001, R2 =
      0.49, median: F = 30.07, p < 0.0001, R2 = 0.58, 10th percentile: F = 31.02, p <
      0.0001, R2 = 0.59, 90th percentile: F = 24.13, p < 0.0001, R2 = 0.52).
      CONCLUSION: BOLD-MRI could reflect the formation and progression of renal
      fibrosis in a rabbit UUO model; however, the value of BOLD-MRI in the long-term
      evaluation of fibrosis is limited.

PMID- 30111498
TI  - Metal ion release barrier function and biotribological evaluation of a zirconium
      nitride multilayer coated knee implant under highly demanding activities wear
      simulation.
AB  - Total knee arthroplasty is a well established treatment for degenerative joint
      disease, which is also performed as a treatment in younger and middle-aged
      patients who have a significant physical activity and high life expectancy.
      However, complications may occur due to biological responses to wear particles,
      as well as local and systemic hypersensitivity reactions triggered by metal ions
      and particles such as cobalt, chromium and molybdenum. The purpose of the study
      was to perform a highly demanding activities (HDA) knee wear simulation in order
      to compare the wear characteristics and metal ion release barrier function of a
      zirconium nitride (ZrN) coated knee implant, designed for patients with suspected
      metal ion hypersensitivity, against an uncoated knee implant made out of CoCrMo.
      The load profiles were applied for 5 million HDA cycles, which represent 15-30
      years of in vivo service depending on the activity level of the patient. Results
      showed a significant wear rate reduction for the coated group (1.01 +/- 0.29
      mg/million cycles) in comparison with the uncoated group (2.89 +/- 1.04
      mg/million cycles). The zirconium nitride coating showed no sign of scratches nor
      delamination during the wear simulation, whereas the uncoated femurs showed
      characteristic wear scratches in the articulation areas. Furthermore, the metal
      ion release from the coated implants was reduced up to three orders of magnitude
      in comparison with the uncoated implants. These results demonstrate the
      efficiency of zirconium nitride coated knee implants to reduce wear as well as to
      substantially reduce metal ion release in the knee joint.

PMID- 30111499
TI  - Corrigendum to "Effect of probiotic supplement on aflatoxicosis and gene
      expression in the liver of broiler chicken" [Environ. Toxicol. Pharmacol. 60
      (2018) 118-127].

PMID- 30111500
TI  - Congenital dislocation of the knee in a three-year-old-child with Larsen
      syndrome: Treatment with a hexapod-type external fixator.
AB  - Congenital knee dislocation (CDK) is a rare condition, and its treatment is
      subject to debate. Here, we report on a new treatment for CDK (using a hexapod
      type external fixator, HEF) in a three-year-old child with Larsen syndrome and
      grade III anterior dislocations of both knees. The left knee was treated with
      serial splints, whereas an HEF was used to treat an irreducible dislocation of
      the right knee. Two HEF aluminium rings were applied surgically. The procedure
      involved a distraction of the knee, then tibial posterior translation, and lastly
      progressive flexion. The clinical and radiological outcomes were good; after four
      years of follow-up, the right knee had stabilized and had a range of motion of
      110 degrees . We conclude that as an innovative, effective option for the
      management of CDK, the use of an HEF may constitute a relatively advantageous
      alternative to quadriceps tenotomy.

PMID- 30111501
TI  - Factors affecting failure of irrigation and debridement with liner exchange in
      total knee arthroplasty infection.
AB  - BACKGROUND: We sought to determine if reoperation-free survival following
      irrigation and debridement with polyethylene liner exchange of acutely infected
      primary TKA is affected by: 1) postoperative antibiotic duration; 2) patient
      characteristics or surgical factors; 3) infecting organism; or 4) whether
      infection was acute postoperative versus hematogenous. METHODS: Of revision TKAs
      from 2004 to 2012 (n = 1735), 76 underwent irrigation and debridement (I&D) with
      liner exchange after primary TKA with mean 3.5-year follow-up. We analyzed those
      requiring reoperation for infection (n = 21) versus those who did not (n = 55).
      RESULTS: Increased duration of postoperative antibiotic therapy (p = 0.0163)
      decreased reoperation for infection. Atrial fibrillation (p = 0.0053), chronic
      obstructive pulmonary disease (COPD) (p = 0.0122), more than 15 cells per high
      powered field (HPF) (p = 0.0124), or higher preoperative C-reactive protein (p =
      0.0025) increased reoperation for infection. Incidence of infection recurrence
      was highest with Methicillin resistant S. aureus (MRSA) and lowest with Gram
      negative organisms. There was no difference in reoperation-free survival between
      acute postoperative and hematogenous infections. CONCLUSION: Reoperation-free
      survival following I&D with polyethylene liner exchange of acutely infected
      primary TKA: 1) improves with increased postoperative antibiotic therapy duration
      so chronic antibiotic suppression should be considered following TKA I&D with
      liner exchange; 2) is worse with atrial fibrillation, COPD, >15 cells/HPF,
      preoperative C-reactive protein >500 mg/L, or MRSA so two-stage revision may be
      favored in these patients; and 3) is equivalent in acute postoperative and
      hematogenous infections.

PMID- 30111502
TI  - Early outcomes of locked noncemented stems for the management of proximal humeral
      fractures: a comparative study.
AB  - BACKGROUND: Proximal humeral fractures are common and a major concern in public
      health resources utilization. There is an increase in the use of reverse total
      shoulder arthroplasty (RTSA) as an option for complex fractures in the elderly.
      The complexity of the technique in RTSA is increased because of the fracture. To
      find an advantage of locking stems in RTSA for the treatment of proximal humeral
      fractures, we designed a comparative study between fracture-dedicated locking
      stems vs. cemented stems. MATERIALS AND METHODS: We retrospectively studied 58
      patients treated with an RTSA after a fracture. We compared how the implant
      design and the tuberosity consolidation affects patient outcome through measuring
      range of motion and the Constant score. RESULTS: The groups were similar in age,
      sex, time to surgery, and Constant score in the uninjured side. Patients treated
      with a dedicated locking noncemented stem performed better, with an increased
      Constant score (P > .05) and reached more mobility with no statistical
      significance. We found that 13 of the 24 fractures (54%) treated with a cemented
      stem consolidated, and 26 of 34 tuberosities (76%) healed in the noncemented
      locked stems. Patients with tuberosity consolidation acquired better range of
      motion and Constant scores (P < .05). CONCLUSIONS: A dedicated stem improves
      tuberosity healing and increases outcomes seen in Constant scores. Tuberosity
      consolidation is a main goal when treating proximal humeral fractures with RTSA.

PMID- 30111503
TI  - Lateralization of the glenosphere in reverse shoulder arthroplasty decreases arm
      lengthening and demonstrates comparable risk of nerve injury compared with
      anatomic arthroplasty: a prospective cohort study.
AB  - HYPOTHESIS: Grammont-style reverse shoulder arthroplasty (RSA) has an increased
      risk of nerve injury compared with anatomic total shoulder arthroplasty (TSA) due
      to arm lengthening. We hypothesized that an RSA with a lateralized glenosphere
      and 135 degrees  neck-shaft angle would reduce humeral lengthening and decrease
      the risk of nerve injury to the level of a TSA. METHODS: The study prospectively
      enrolled 50 consecutive patients undergoing RSA (n = 30) or TSA (n = 20) as
      determined by a power analysis based on previous research for our institution.
      Intraoperative neuromonitoring was used to detect nerve alerts during 4 distinct
      stages of the procedure. Preoperative and postoperative arm lengths were measured
      on scaled radiographs. Patients were examined immediately postoperatively and at
      follow-up visits for neurologic complications. RESULTS: Mean motor and sensory
      nerve alerts per case were similar for TSA and RSA (motor: TSA, 1.5 +/- 2; RSA,
      1.5 +/- 2; P = .96; sensory: TSA, 0.6 +/- 0.9; RSA, 0.2 +/- 0.6; P = .06). The
      mean change in arm length was 3 +/- 7 mm in the TSA cohort vs. 14 +/- 7 mm in the
      RSA cohort (P = .0001). Temporary neurologic changes postoperatively were noted
      in 1 TSA and 1 RSA patient, amounting to a 4% incidence of nerve injury.
      CONCLUSIONS: An RSA design with a lateralized glenosphere and a lower neck-shaft
      angle decreases arm lengthening compared with the Grammont design. The reduction
      in lengthening appears to eliminate the historically increased risk of neurologic
      injury associated with RSA relative to TSA.

PMID- 30111505
TI  - Iatrogenic bipolar clavicular instability managed with clavicular lengthening and
      sternoclavicular and acromioclavicular stabilization: a case report.

PMID- 30111504
TI  - Blood flow evaluation by dynamic magnetic resonance imaging of symptomatic
      rotator cuff tears and frozen shoulders.
AB  - BACKGROUND: This study compared imaging findings of blood flow changes between
      symptomatic rotator cuff tear (RCT) and frozen shoulder (FS) by using 3
      dimensional dynamic magnetic resonance imaging (MRI) to determine the clinical
      characteristics of symptomatic RCT. METHODS: The 2 study groups comprised 31
      symptomatic RCT patients who underwent arthroscopic rotator cuff repair and 30
      patients with FS. We denoted abnormal blood flow detected around the glenohumeral
      joint as the burning sign (BS). We evaluated the characteristics of dynamic MRI
      and compared them between BS-positive and BS-negative patients in the RCT group.
      RESULTS: All members of the FS group showed the BS. Conversely, the incidence of
      the BS in RCT patients was 53% (16 of 31). The BS in RCT and FS patients was
      observed in the rotator interval in 16 shoulders, in the axillary pouch in 3
      shoulders (P < .01), and in the intertubercular groove in 10 RCT and 12 FS
      patients. In the RCT group, 16 patients with BS had a statistically significantly
      higher Numeric Rating Score at rest (P = .0005) and in motion (P = .04) than the
      15 patients without BS and exhibited a higher rate of small and medium tears and
      a higher rate of shoulder contracture. CONCLUSION: Dynamic MRI of symptomatic RCT
      (53.3%) highlighted abnormal vascularization around the glenohumeral joint, which
      may be associated with pain and contracture in RCT as in FS.

PMID- 30111506
TI  - Innovation in shoulder surgery: the impact on our patients.

PMID- 30111507
TI  - Coronary artery compression from epicardial leads: More common than we think.
AB  - BACKGROUND: A child with an epicardial pacemaker presented with sudden death at
      our institution, secondary to coronary artery compression. This case prompted
      enhanced surveillance of all patients with epicardial pacing or defibrillation
      systems. OBJECTIVE: The purpose of this study was to determine the incidence of
      coronary artery compression and the diagnostic yield of catheter angiography (CA)
      and computed tomography (CT). METHODS: All patients with epicardial leads who
      underwent CA or cine CT were retrospectively reviewed. A patient with postmortem
      diagnosis of coronary compression was also included. RESULTS: Coronary
      compression was noted in 8 of 145 patients (5.5%) with epicardial leads. Median
      age at diagnosis was 11.4 years (range 3.0-29.6 years). Six patients had
      compression noted by CA, 6 by CT, and 1 by postmortem analysis. Chest radiography
      had sensitivity and specificity of 57% and 96%, respectively; CT 100% and 93%,
      respectively; and CA 86% and 100%, respectively. There was no difference in age
      or weight at the time of lead implant between those who did and those who did not
      have compression (age: median 1.3 vs 2.4 years; P = .36; weight: 9.5 vs 11.8 kg;
      P = .46). Among those with coronary compression, 6 of 8 (75%) had symptoms (1
      sudden death, 3 chest pain [2 with associated troponin leak]), 2 unexplained
      fatigue). Seven patients had surgical repositioning of their lead. CONCLUSION: We
      found a higher incidence of coronary artery compression by epicardial leads
      (5.5%) than previously reported in the literature. Chest radiography can serve as
      a good surveillance tool, with cine CT scans considered in those with concerning
      radiographs or with symptoms. Confirmatory CA can be performed before surgical
      intervention.

PMID- 30111508
TI  - More epicardial electrode issues to remember.

PMID- 30111509
TI  - Impact of Enlarged Nonhypermetabolic Lymph Nodes on Outcomes After Stereotactic
      Body Radiotherapy for Early-Stage Non-Small-Cell Lung Cancer.
AB  - BACKGROUND: Up to 15% of patients undergoing positron emission tomography
      (PET)/computed tomography (CT) before stereotactic body radiotherapy (SBRT)
      harbor occult nodal disease. In the absence of invasive mediastinal staging, the
      clinical significance of enlarged nonhypermetabolic lymph nodes (LNs) remains
      unclear. We performed what is to our knowledge the first study to address whether
      enlarged nonhypermetabolic LNs were associated with higher post-SBRT failure
      rates. PATIENTS AND METHODS: Two academic centers assessed 157 consecutive
      patients treated with SBRT for cT1-2aN0M0 non-small-cell lung cancer who
      underwent PET/CT without pathologic nodal staging. The cutoff of an enlarged node
      was >= 1.0 cm, although a 7 mm threshold was also evaluated. Local recurrence
      free survival (RFS), regional RFS, distant metastasis-free survival, RFS, and
      overall survival (OS) were calculated by Kaplan-Meier methodology. Multivariate
      Cox modeling addressed factors associated with RFS and OS. RESULTS: There were
      120 patients (76%) with LNs < 1 cm and 37 (24%) with nodes >= 1 cm. Most patients
      had peripheral and/or T1 tumors. Median follow-up was 25.5 months. There were no
      differences between cohorts in actuarial local RFS, regional RFS, distant
      metastasis-free survival, RFS, or OS (P > .05 for all). Thirteen percent of
      patients experienced any nodal relapse, 15% of which occurred in the same station
      as that of the largest pre-SBRT LN. Stratification by largest LN location in an
      N1 versus N2 station showed no differences in RFS or OS (P > .05 for both). A 7
      mm cutoff also showed no differences in outcomes (P > .05 for all). LN size was
      not correlated with RFS/OS on multivariable analysis (P > .05 for both).
      CONCLUSION: The presence of enlarged nonhypermetabolic LNs on PET/CT is not
      associated with increased post-SBRT failure rates.

PMID- 30111511
TI  - Proper zinc evaluation in clinical practice: Effect of sample type and it's
      stability.
AB  - Zinc (Zn) is a ubiquitous element that plays a vital role in the growth and
      development of human body. Traditionally, Zn has been measured in plasma samples
      using "trace element" dedicated sampling tubes. However, the recent increase in
      its assessment leads to the need to use others than plasma samples and the use of
      sera could be a justified and valid alternative. We evaluated the differences
      between plasma and serum, for Zn quantification. 307 blood paired samples from
      patients enrolled for the treatment of obesity-related pathology at our out
      patient department were assessed. The quantification of Zn was performed by Flame
      atomic absorption spectroscopy. Using 123 serum samples randomly selected from
      our own biobank and stored at -80  degrees C for 5 years, we further investigated
      the long-term stability of serum Zn. The mean result for Zn was 77.8 +/- 13.2
      MUg.dL-1 and 77.4 +/- 12.8 MUg.dL-1, respectively for plasma and for serum, (p =
      0.43). Bland-Altman analyses demonstrated excellent concordance of the assay in
      the two different blood matrices. The mean difference +/- SD between serum and
      plasma matrices was 0.32 +/- 3.40 MUg.dL-1. The assessment of serum Zn long-term
      stability indicated a significant change after 5 years storage. The mean value
      was 74.2 +/- 10.9 MUg.dL-1 for fresh samples and 83.3 +/- 10.9 MUg.dL-1 after 5
      years of storage at -80  degrees C, corresponding to a mean difference of +9.1
      MUg.dL-1(+10,9%, p < 0.05). The increase in Zn values described after long-term
      storage has to be considered though that should not have a significant clinical
      value. In conclusion, the routine measurement of Zn can be made in an accurate
      way using a serum sample, without the need for a specific tube for trace elements
      assessment.

PMID- 30111510
TI  - Diagnostic concordance between NT-proBNP and BNP for suspected heart failure.
AB  - OBJECTIVES: BNP and NT-proBNP are viewed as comparable in their ability to
      diagnose and monitor HF in clinical guidelines. However, no recent large-scale
      study has directly established diagnostic concordance between BNP and NT-proBNP.
      This study sought to assess diagnostic concordance of BNP and NT-proBNP for
      ruling in and ruling out heart failure (HF). METHODS: Simultaneous BNP and NT
      proBNP testing was performed on 2729 patient samples with routinely ordered BNP
      testing. Hospital location, age, sex, creatinine, BNP and NT-proBNP were also
      recorded. Recommended cutoffs for BNP and NT-proBNP for ruling in and out HF were
      used for assessing diagnostic concordance and correlation. RESULTS: In the ED
      setting, concordance between BNP and NT-proBNP was 0.695 (95% CI, 0.668-0.723) by
      weighted kappa using the recommended cutoffs for the acute setting. In non-ED
      patients, the concordance was 0.642 (95% CI, 0.580-0.705) using non-acute setting
      cutoffs. In the ED setting, patients with eGFR <60 mL/min/1.73m2 had lower
      overall concordance (0.626; 95% CI 0.580-0.672) compared to those with eGFR >60
      mL/min/1.73m2 (0.707, 95% CI 0.669-0.744). Patients with an eGFR <15
      mL/min/1.73m2 had a much higher ratio of NT-proBNP to BNP than patients with eGFR
      >60 mL/min/1.73m2 (17.0 vs. 4.7, P < .001). Linear regression revealed an r2 of
      0.52 in the ED setting and 0.49 in the non-ED setting between BNP and NT-proBNP.
      For 368 patients with multiple measurements of natriuretic peptides, 19.7% of
      paired temporal measurements had an increase in one peptide and a decrease in the
      other. CONCLUSION: The current cutoffs for diagnosing HF for NT-proBNP and BNP
      have relatively low diagnostic concordance and correlation, particularly among
      patients with chronic kidney disease.

PMID- 30111512
TI  - miR-590-5p suppresses hepatocellular carcinoma chemoresistance by targeting YAP1
      expression.
AB  - BACKGROUND: Resistance to chemotherapeutic treatment is a common phenomenon in
      cancers, especially in hepatocellular carcinoma (HCC). The Hippo signaling
      pathway has been demonstrated to play a role in tumor initiation, development,
      and progression. However, little is known about its roles in the HCC
      chemoresistance. METHODS: In this study, real-time PCR and western blotting were
      used to identify the expression profile of key components of Hippo signaling
      pathway between chemoresistant and chemosensitive HCC cell lines. In vitro and in
      vivo loss- and gain-of-function studies were performed to reveal the effects and
      related mechanism of microRNA-590-5p/YAP1 axis in the chemoresistant phenotype of
      HCC cells. FINDINGS: We identified yes-associated protein 1 (YAP1) as the major
      dysregulated molecules in adriamycin (ADR)-resistant HCC cells. YAP1 was
      profoundly implicated in the chemoresistant phenotype of HCC cells. Furthermore,
      microRNA-590-5p was revealed as a functional modulator of YAP1. Importantly, YAP1
      mediated chemoresistant phenotype was closely related to increased expression of
      stemness markers and ATP-binding cassette transporters. HCC patients with poor
      response to transarterial chemoembolization (TACE) treatment had higher protein
      level of YAP1 than that in the responsive patients. INTERPRETATION: The microRNA
      590-5p/YAP axis plays an important role in the chemotherapeutic resistance of HCC
      cells, suggesting new adjuvant chemotherapeutic directions in HCC. FUND: National
      Natural Science Foundation of China, Zhejiang Province Medical and Health Care
      Key Project, Experimental Animal Science and Technology Projects of Zhejiang
      Province, Public Welfare Technology Application Research Project of Lishui,
      Chinese Medicine Science and Technology Projects of Zhejiang Province.

PMID- 30111513
TI  - Identification of determinants associated with uptake of the first dose of the
      human papillomavirus vaccine in Denmark.
AB  - BACKGROUND: The human papillomavirus vaccine (HPV vaccine) was introduced into
      the Danish Childhood Vaccination Programme in 2009. Following a national debate
      questioning the safety of the vaccine, the coverage decreased from an uptake of
      >90% for the first dose of the HPV vaccine to an uptake of 52% in girls born in
      2003. The aim of this study was to identify changes in determinants for HPV
      vaccine hesitancy in the period when the debate spiraled and to identify
      determinants for specific hesitancy towards the HPV vaccine among girls who
      received the second dose of the measles, mumps and rubella vaccine. METHODS: We
      included girls born in the period 1999-2003 who were residing in Denmark between
      their 12th and 13th birthday (n = 161,528). Data from the Danish Vaccination
      Register were linked with demographic data from the Danish Civil Registration
      System. We used multiple logistic regression models to identify associations
      between determinants and the uptake of the first dose of the HPV vaccine (HPV1).
      RESULTS: For girls born in 1999-2000, low uptake was seen in children of
      increasing birth order, young or old age of mother, non-Danish origin, low uptake
      of other childhood vaccines, and in girls living with one parent. For girls born
      in 2001-2003, most of these determinants of low uptake became less significant.
      Birth order and origin showed different tendencies when comparing birth cohorts
      1999-2000 with birth cohorts 2001-2003. CONCLUSIONS: We found demographic
      disparities in the uptake of HPV1 that were generally in line with existing
      literature. More importantly, the results indicate that determinants for
      hesitancy towards the HPV vaccines changed during a period of intense public
      debate regarding the safety of the HPV vaccine. This may indicate that the public
      concerns over safety disproportionally affect those who trusted vaccines prior to
      the debate.

PMID- 30111514
TI  - Phage vaccines displaying YGKDVKDLFDYAQE epitope induce protection against
      systemic candidiasis in mouse model.
AB  - Candida albicans is a common commensal and opportunistic fungal pathogen in
      human, which poses threat to human health, especially in immunocompromised
      patients. Unfortunately, few effective prophylactic and therapeutic strategies
      were applied to clinic practice. Recently, the peptide YGKDVKDLFDYAQE from
      Fructose-bisphosphate aldolase 1 (Fba1), as a vaccine, was reported to induce
      protection effects against systemic candidiasis. Here, we displayed this epitope
      peptide on the coat proteins (pIII or pVIII) of filamentous phage, and
      investigated their protective effects against C. albicans infections. Mice were
      immunized with recombinant phages (designated as phage-3F and phage-8F) or
      protein (rFba1), then challenged with C. albicans yeast cells via lateral tail
      vein. Results demonstrated that the recombinant phages as well as rFba1
      apparently induced humoral and cellular immune responses, reduced fungal burden
      and relieved kidney damage in infected mice and significantly improved their
      survival rates. Briefly, all these findings indicated that the recombinant phages
      displaying the epitope YGKDVKDLFDYAQE have the potential to be developed into a
      new vaccine against C. albicans infections.

PMID- 30111516
TI  - Correction to Lancet Glob Health 2018; 6: e732.

PMID- 30111515
TI  - Effectiveness of post-exposure prophylaxis during varicella outbreaks among
      primary and middle school students in Shanghai: An analysis of three-year
      surveillance data.
AB  - OBJECTIVES: To evaluate the effectiveness of post-exposure prophylaxis conducted
      during varicella outbreaks among students in Shanghai. METHODS: Surveillance data
      were collected from September 1, 2013 to December 31, 2016 involving 3524
      susceptible students in 109 primary and middle school classes where emergency
      vaccinations (EVs) had been administered. Students were divided into two groups
      according to their prior vaccination (PV) varicella vaccine status. A secondary
      attack rate was used to compare EV and non-EV groups using a chi-squared test.
      Stratification analyses were performed, adjusting for the EV administration date,
      the vaccination coverage rate, and the number of cases prior to the EV. RESULTS:
      The effectiveness rate was 92.2% (95% confidence interval (CI): 37.1-99.0%) when
      EV was applied within 3 days following the outbreak onset date, and 95.2% (95%
      CI: 79.9-98.8%) when vaccination coverage was >=80% among students with PV. When
      students with PV received an EV for varicella within 3 days, the effectiveness
      rate was 100%. CONCLUSIONS: EV showed high protective effectiveness for varicella
      during outbreaks, especially if administered within 3 days of an outbreak and in
      conjunction with a high coverage rate.

PMID- 30111517
TI  - Power of Judgment: The Significance of Kant's Philosophy for the Medical System
      Today.
AB  - The ways of thinking in the manufacturing sciences are increasingly determining
      the rationality within medicine as a practical or action-based science. This
      "technological paradigm" infiltrates the field of medicine with the promise of
      increasing efficiency while simultaneously improving quality at various points in
      the system. Simple linear causal relationships generally need to be taken into
      account when manufacturing products. Even complex manufacturing processes can be
      broken down into the smallest units and, therefore, also be automated. The
      situation in complex systems such as the human body, however, is completely
      different. In order for doctors to be able to carry out their actions within this
      complex system, medicine as a science provides the physician with rules on the
      means that should be used to decide which remedy should be used, when and how.
      This judgment of which remedy should be used, when and how, what is known as the
      indication, is a central medical moment. This requires a power of judgment
      sharpened by experience. The indication, in turn, essentially determines the
      course of a disease and thus the quality of the treatment or the quality of
      result so often referred to these days.

PMID- 30111518
TI  - Health Career Academy: Addition of a Surgical Case-Based Learning Curriculum
      Captures the Interest of High School Students.
AB  - OBJECTIVE: The Health Career Academy (HCA) is a national program which provides a
      structure to introduce underserved high school students to healthcare careers.
      Utilizing the HCA framework, we adapted the curriculum to emphasize surgical
      cases and invited physicians to enrich the learning experience. DESIGN, SETTING,
      AND PARTICIPANTS: Medical students adapted a surgical case-based learning (CBL)
      curriculum at a local high school serving students from a primarily ethnic
      minority and low-income community (61% Black, 20% Hispanic; 58% free or reduced
      lunch). Each grade level received a minimum of ten, 90-minute CBL sessions.
      Expert faculty lecturers supplemented lessons. Medical student volunteers and
      10th and 11th grade students completed postsemester surveys. RESULTS: Over four
      semesters, HCA held 44 sessions, with 81 students graduating from the program. A
      total of 66% of sessions featured at least one faculty volunteer. A total of 36
      students in 10th and 11th grade and 15 medical student volunteers completed
      postparticipation surveys. A total of 46.2% of 11th grade students previously
      participated in the 10th grade curriculum. On a scale of 1 to 4, students rated
      HCA highly in its overview of career options (mean 3.61, [SD 0.5]) and instilling
      understanding of patient care (3.78 [0.42]). Students enjoyed learning about
      career paths (3.61 [0.50]) and health topics (3.83 [0.39]). Of 10th and 11th
      grade students, 100% considered a healthcare career, with 34.8% of 10th and 61.5%
      of 11th grade students expressing interest in pursuing a surgical specialty.
      After volunteering, medical students felt like better educators (4.47 [0.64]) and
      were more likely to pursue teaching roles (4.2 [0.86]). CONCLUSIONS: The Duke HCA
      chapter implemented the HCA program featuring CBL sessions emphasizing surgical
      cases. This program engaged minority students and potentially contributed to
      student interest in surgical careers. It helped to prepare medical students for
      future teaching roles. An interactive, surgery-focused program may increase the
      number of minority youth interested in pursuing health careers.

PMID- 30111519
TI  - Uncovering Cultural Barriers to Quality Improvement Learning in a Trauma Program:
      An Ethnographic Study.
AB  - OBJECTIVE: Quality improvement (QI) training is an essential component of
      postgraduate surgical education and can occur through formal and informal
      education programs. Informal QI education requires that faculty take advantage of
      learning opportunities in the hospital setting. Trauma rotations appear ideal
      opportunities for informal QI learning given that performance improvement is a
      mandatory component of care at verified trauma centers. It is unclear, however,
      whether QI initiatives within trauma programs are well integrated into trainee
      education. This study explored the QI learning environment in a level 1 academic
      trauma center. STUDY DESIGN: An ethnographic study using observation and
      interviews methods. The theoretical lens of hidden curriculum was used to
      interpret the data and generate hypotheses around faculty and trainee
      experiences. SETTING: University of Toronto and Sunnybrook Health Sciences
      Center. PARTICIPANTS: Twenty-seven observations involving more than 50 faculty
      and trainees; seventeen interviews with faculty and surgical trainees. RESULTS:
      All faculty and trainees endorsed QI and informal QI learning. Discrepant
      experiences were found regarding opportunities to learn and do QI in the clinical
      setting. Faculty viewed themselves as perpetually doing and teaching QI while
      trainees perceived little to no QI learning. Trainees identified Morbidity and
      Mortality rounds as the main opportunity for QI learning; however, traditional
      teaching style through "pimping" and a largely clinical focus acted as barriers
      to QI education. Furthermore, trainees chiefly viewed QI as service to the
      institution, rather than as a form of learning, which contributed to their
      disinterest in taking up informal QI lessons. CONCLUSION: Informal QI education
      is highly valued and desired in academic trauma centers but enduring teaching
      methods, inconsistencies in the cultural learning environment and a hidden
      curriculum devaluing QI learning are persistent barriers to change.

PMID- 30111520
TI  - Sex and Long-Term Outcomes After Implantation of Absorb Bioresorbable Vascular
      Scaffold for Treatment of Coronary Artery Disease.
AB  - AIMS: Women and men suffering of coronary artery disease differ in their risk
      profile. We sought to investigate the impact of sex on 2-year outcomes after BVS
      implantation in routine clinical practice. METHODS AND RESULTS: Sex-based
      analysis of clinical outcomes was done by pooling the individual patient data of
      ISAR-ABSORB and KUM-ABSORB registries performed in 4 high-volume tertiary centers
      in Munich. Of the total of 1032 patients, 259 (25.1%) were women. The primary
      composite endpoint of death, target-vessel myocardial infarction (TV-MI) and
      target lesion revascularization (TLR) through 2 years occurred in 13.2% of women
      and 17.9% of men (p = 0.12). Compared to men, women experienced numerically lower
      rates of TLR and definite or probable BVS thrombosis - 7.5% vs. 12.4% (p=0.051)
      and 1.2% and 2.7% (p=0.20), respectively. Independent predictors of increased
      risk for TLR were use of smaller size BVS (HR 1.28, 95% CI 1.02-1.62), while
      being women was a protective factor (HR 0.59, 95% CI 0.35-1.00). CONCLUSIONS: BVS
      used in routine setting tends to perform better among women compared to men,
      which might be partially related to their lower complexity of coronary artery
      disease.

PMID- 30111521
TI  - Radial versus femoral artery access in patients undergoing PCI for left main
      coronary artery disease: analysis from the EXCEL trial.
AB  - AIMS: We sought to compare clinical outcomes and procedural characteristics with
      transradial access (TRA) versus transfemoral access (TFA) in patients who were
      treated with PCI for left main (LM) coronary artery disease. METHODS AND RESULTS:
      The EXCEL trial was a prospective, international, open-label, multicentre trial
      that randomised 1,905 patients with LM disease and SYNTAX scores <=32 to PCI with
      everolimus-eluting stents versus coronary artery bypass grafting. The present
      analysis cohort consisted of 931 patients undergoing PCI with TRA or TFA, but not
      both. The primary endpoint was a composite of death, myocardial infarction (MI),
      or stroke at three years. Multivariable Cox proportional hazards regression was
      used to adjust for differences in baseline covariates. PCI in EXCEL was performed
      exclusively with TRA in 248 (26.6%) patients and with TFA in 683 (73.4%)
      patients. TRA patients were younger and less likely to have hypertension and
      chronic kidney disease. The mean number of vessels and lesions treated was higher
      in TFA patients, although the SYNTAX score was similar in both groups. Patients
      undergoing TRA and TFA had similar 30-day rates of TIMI major or minor bleeding
      (2.4% versus 3.8%, respectively, p=0.30). At three years, TRA and TFA patients
      had similar rates of the primary endpoint (15.7% versus 14.8%, adjusted HR 1.11,
      95% CI: 0.73-1.69, p=0.64), as well as the individual rates of death, MI, stroke,
      ischaemia-driven revascularisation and stent thrombosis. CONCLUSIONS: In the
      EXCEL trial, PCI of LM disease with TRA was associated with comparable early and
      late clinical outcomes to TFA.

PMID- 30111522
TI  - Early commercial experience from transcatheter aortic valve implantation using
      the PorticoTM bioprosthetic valve: 30-day outcomes in the multicentre PORTICO-1
      study.
AB  - AIMS: The aim of this study was to investigate the procedural and short-term
      outcomes of transcatheter aortic valve implantation (TAVI) with the PorticoTM
      self-expanding, resheathable TAVI system from an ongoing long-term multicentre
      study. METHODS AND RESULTS: A total of 941 patients (82.4+/-5.9 years, 65.7%
      female, STS score 5.8+/-4.9%) with severe symptomatic aortic stenosis underwent
      TAVI using the Portico bioprosthesis. Patients were clinically and
      echocardiographically assessed at implantation, discharge and 30 days post TAVI.
      An independent CEC and core laboratory adjudicated adverse events (according to
      VARC-2) and follow-up echocardiograms, respectively. Implantation was successful
      in 96.0% of patients. Thirty-day all-cause, cardiovascular mortality and
      disabling stroke rates were 2.7%, 2.4% and 1.6%, respectively. Major vascular
      complications and life-threatening bleeding occurred in 5.5% and 3.1% of
      patients, respectively. A new pacemaker was implanted in 18.7% of patients.
      Aortic valve area (0.70+/-0.33 cm2 vs. 1.79+/-0.48 cm2) and transvalvular
      gradient (49.7+/-15.3 mmHg vs. 8.6+/-3.9 mmHg) improved significantly. The 30-day
      rate of moderate or higher paravalvular leak (PVL) was 3.9%. CONCLUSIONS: The
      Portico TAVI system allows safe and effective treatment of aortic stenosis in
      patients at increased surgical risk. At 30 days, mortality was low, and good
      haemodynamic performance was indicated by low transvalvular gradient and a low
      rate of moderate or higher PVL.

PMID- 30111523
TI  - Insights from eight years of adoption experience of transcatheter mitral valve
      repair in Germany: observed utilisation patterns and impact on overall mitral
      valve procedure volumes.
AB  - AIMS: The German healthcare system was among the first to introduce transcatheter
      mitral valve repair (TMVR) into routine care. The objective of this study was to
      analyse adoption and utilisation patterns and to estimate the impact of TMVR
      availability on mitral valve (MV) procedure volumes in the first eight years
      after commercialisation. METHODS AND RESULTS: Procedure volumes were collected
      from German Federal Statistics Office databases for TMVR and mitral valve surgery
      (MVS) from 2008-2015. Procedure volumes were stratified by age group (<65, 65-74,
      75-84, >=85 years). Overall procedure volumes grew from 14,525 to 24,898 (+71%).
      MVS procedures grew from 14,477 to 20,402 (+41%) (p=0.008). The proportion of
      TMVR procedures grew from 0.3% (48 procedures) to 18.1% (4,496 procedures)
      (p=0.008). In 2015, TMVR use reached 5%, 15%, 31%, and 68% of overall MV
      procedures in the studied age groups (<65, 65-74, 75-84, >=85 years). MVS volumes
      grew in all age groups, with the highest increase in the age group <65 (+2,945).
      CONCLUSIONS: The availability of TMVR has contributed to a pronounced increase in
      MV procedure volumes in Germany. Simultaneously, MVS procedure volumes continued
      to grow substantially. The highest increase of TMVR was observed in elderly
      populations, suggesting referral of patients with MV disease previously left
      untreated.

PMID- 30111524
TI  - Neonatal Screening for Congenital Adrenal Hyperplasia in Turkey: A Pilot Study
      with 38,935 Infants.
AB  - BACKGROUND: Congenital adrenal hyperplasia (CAH) is the most common form of
      primary adrenal insufficiency in children. Neonatal screening for CAH is
      effective in detecting the salt-wasting form and reducing mortality. AIM: To
      estimate incidence of CAH in Turkey and to assess the characteristics and
      efficacy of the adopted newborn CAH screening strategy. METHOD: A pilot newborn
      CAH screening study was carried out under the authority of Turkish Directorate of
      Public Health. Newborn babies >=32 gestational weeks and >=1500 gr birth weight
      from four cities between March 27- September 15, 2017 were included. Screening
      protocol included one sample two-tier testing. In the first step, 17alpha
      hydroxyprogesterone (17-OHP) was measured by fluoroimmunoassay in dried blood
      spots obtained at 3-5th days of life. The cases with positive initial screening
      were tested by steroid profiling in dried blood spots using liquid chromatography
      tandem mass spectrometry method to measure 17-OHP, 21-deoxycortisol, cortisol, 11
      deoxycortisol and androstenedione as a second-tier test. The babies with steroid
      ratio of (21-deoxycortisol+17-OHP)/cortisol>=0.5 were referred to pediatric
      endocrinology clinics fordiagnostic assessment. RESULTS: 38,935 infants were
      tested, 2265 (5.82%) had second-tier testing, and 212 (0.54%) were referred for
      clinical assessment, 6 of whom were diagnosed with CAH (four males, two females).
      Four cases were identified as salt-wasting 21-hydroxylase deficiency (21-OHD) (2
      males,2 females), one male baby had simple virilizing 21-OHD, one male baby had
      11-OHD CAH. The incidence of classical 21-OHD in the screened population was
      1:7,787. CONCLUSION: The incidence of CAH due to classical 21-OHD is higher in
      Turkey in comparison to previous reports. Thus, it is suggested to add CAH to
      newborn screening panel in Turkey. The use of steroid profiling as a second-tier
      test improves the efficacy of the screening and reduces false-positives.

PMID- 30111526
TI  - Using Smartphone Apps to Promote Psychiatric Rehabilitation in a Peer-Led
      Community Support Program: Pilot Study.
AB  - BACKGROUND: Management of severe and persistent mental illness is a complex,
      resource-intensive challenge for individuals, their families, treaters, and the
      health care system at large. Community-based rehabilitation, in which peer
      specialists provide support for individuals managing their own condition, has
      demonstrated effectiveness but has only been implemented in specialty centers. It
      remains unclear how the peer-based community rehabilitation model could be
      expanded, given that it requires significant resources to both establish and
      maintain. OBJECTIVE: Here, we describe the results from a study of one such
      program implemented within Waverley Place, a community support program at McLean
      Hospital, emphasizing psychiatric rehabilitation for individuals with severe and
      persistent mental illness, as well as describing the challenges encountered
      during the implementation of the program. Key questions were whether the patients
      could, and would, successfully use the app. METHODS: The smartphone app offered
      multiple features relevant to psychiatric rehabilitation, including daily task
      lists, activity tracking, and text messaging with peer specialists. A 90-day
      program of activities, goals, and content specific to the community support
      program was created on the basis of a prior pilot, in collaboration between
      members of the app development team (WellFrame), and peers, clinical, and
      research staff associated with the program. Hospital research staff recruited
      patients into the study, monitored peer and patient engagement, and handled all
      raw data acquired from the study. RESULTS: Of 100 people approached for the
      study, a total of 13 provided consent, of which 10 downloaded and used the app.
      Two patients were unable to complete the app installation. Five used the app
      regularly as part of their daily lives for at least 20 days of the 90-day
      program. We were unable to identify any specific factors (eg, clinical or
      demographic) that affected willingness to consent or engage with the app platform
      in the very limited sample, although the individuals with significant app use
      were generally satisfied with the experience. CONCLUSIONS: Smartphone apps may
      become a useful tool for psychiatric rehabilitation, addressing both psychiatric
      and co-occurring medical problems. Individualizing functions to each patient and
      facilitating connection with a certified peer specialist may be an important
      feature of useful apps. Unlike prior reports emphasizing that patients with
      schizophrenia will adopt smartphone platforms, we found that implementation of
      digital tools into existing community support programs for severe and persistent
      mental illness has many challenges yet to be fully overcome to realize the
      potential benefits such apps could have to promote systematization and cost
      reduction for psychiatric rehabilitation.

PMID- 30111525
TI  - A Face-Aging App for Smoking Cessation in a Waiting Room Setting: Pilot Study in
      an HIV Outpatient Clinic.
AB  - BACKGROUND: There is strong evidence for the effectiveness of addressing tobacco
      use in health care settings. However, few smokers receive cessation advice when
      visiting a hospital. Implementing smoking cessation technology in outpatient
      waiting rooms could be an effective strategy for change, with the potential to
      expose almost all patients visiting a health care provider without preluding
      physician action needed. OBJECTIVE: The objective of this study was to develop an
      intervention for smoking cessation that would make use of the time patients spend
      in a waiting room by passively exposing them to a face-aging, public morphing,
      tablet-based app, to pilot the intervention in a waiting room of an HIV
      outpatient clinic, and to measure the perceptions of this intervention among
      smoking and nonsmoking HIV patients. METHODS: We developed a kiosk version of our
      3-dimensional face-aging app Smokerface, which shows the user how their face
      would look with or without cigarette smoking 1 to 15 years in the future. We
      placed a tablet with the app running on a table in the middle of the waiting room
      of our HIV outpatient clinic, connected to a large monitor attached to the
      opposite wall. A researcher noted all the patients who were using the waiting
      room. If a patient did not initiate app use within 30 seconds of waiting time,
      the researcher encouraged him or her to do so. Those using the app were asked to
      complete a questionnaire. RESULTS: During a 19-day period, 464 patients visited
      the waiting room, of whom 187 (40.3%) tried the app and 179 (38.6%) completed the
      questionnaire. Of those who completed the questionnaire, 139 of 176 (79.0%) were
      men and 84 of 179 (46.9%) were smokers. Of the smokers, 55 of 81 (68%) said the
      intervention motivated them to quit (men: 45, 68%; women: 10, 67%); 41 (51%) said
      that it motivated them to discuss quitting with their doctor (men: 32, 49%;
      women: 9, 60%); and 72 (91%) perceived the intervention as fun (men: 57, 90%;
      women: 15, 94%). Of the nonsmokers, 92 (98%) said that it motivated them never to
      take up smoking (men: 72, 99%; women: 20, 95%). Among all patients, 102 (22.0%)
      watched another patient try the app without trying it themselves; thus, a total
      of 289 (62.3%) of the 464 patients were exposed to the intervention (average
      waiting time 21 minutes). CONCLUSIONS: A face-aging app implemented in a waiting
      room provides a novel opportunity to motivate patients visiting a health care
      provider to quit smoking, to address quitting at their subsequent appointment and
      thereby encourage physician-delivered smoking cessation, or not to take up
      smoking.

PMID- 30111527
TI  - Effectiveness of Serious Gaming During the Multidisciplinary Rehabilitation of
      Patients With Complex Chronic Pain or Fatigue: Natural Quasi-Experiment.
AB  - BACKGROUND: Current evidence for the effectiveness of specialist
      multidisciplinary programs for burdensome chronic pain and functional somatic
      syndromes drives the effort to improve approaches, strategies, and delivery
      modes. It remains unknown to what extent and in what respect serious gaming
      during the regular outpatient rehabilitation can contribute to health outcomes.
      OBJECTIVE: The objectives of our study were to determine the effect of additional
      serious gaming on (1) physical and emotional functioning in general; (2)
      particular outcome domains; and (3) patient global impressions of change, general
      health, and functioning and to determine (4) the dependency of serious gaming
      effects on adherence. METHODS: We conducted a naturalistic quasi-experiment using
      embedded qualitative methods. The intervention group patients received an
      additional guided (mindfulness-based) serious gaming intervention during weeks 9
      12 of a 16-week rehabilitation program at 2 sites of a Dutch rehabilitation
      clinic. Simultaneously, 119 control group patients followed the same program
      without serious gaming at 2 similar sites of the same clinic. Data consisted of
      10 semistructured patient interviews and routinely collected patient self
      reported outcomes. First, multivariate linear mixed modeling was used to
      simultaneously estimate a group effect on the outcome change between weeks 8 and
      16 in 4 primary outcomes: current pain intensity, fatigue, pain catastrophizing,
      and psychological distress. Second, similar univariate linear mixed models were
      used to estimate effects on particular (unstandardized) outcomes. Third,
      secondary outcomes (ie, global impression of change, general health, functioning,
      and treatment satisfaction) were compared between the groups using independent t
      tests. Finally, subgroups were established according to the levels of adherence
      using log data. Influences of observed confounding factors were considered
      throughout analyses. RESULTS: Of 329 eligible patients, 156 intervention group
      and 119 control group patients (N=275) with mostly chronic back pain and
      concomitant psychosocial problems participated in this study. Of all, 119
      patients played >=75% of the game. First, the standardized means across the 4
      primary outcomes showed a significantly more favorable degree of change during
      the second part of the treatment for the intervention group than for the control
      group (beta=-0.119, SE=0.046, P=.009). Second, the intervention group showed a
      greater outcome change in depressive mood (b=-2.748, SE=1.072, P=.011) but not in
      "insufficiency" or concentration problems. Third, no significant group effects on
      secondary outcomes were found. Fourth, adherence was generally high and
      invariant. CONCLUSIONS: The findings of this study suggest a very small favorable
      average effect on relevant health outcomes of additional serious gaming during
      multidisciplinary rehabilitation. The indication that serious gaming could be a
      relatively time-efficient component warrants further research into if, when, how,
      and for which patients serious gaming could be cost-effective in treatment and
      why. TRIAL REGISTRATION: Netherlands Trial Registry NTR6020;
      http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6020 (Archived by
      WebCite at http://www.webcitation.org/71IIoTXkj).

PMID- 30111528
TI  - Intra-Arterial TheraSphere Yttrium-90 Glass Microspheres in the Treatment of
      Patients With Unresectable Hepatocellular Carcinoma: Protocol for the STOP-HCC
      Phase 3 Randomized Controlled Trial.
AB  - BACKGROUND: Globally, hepatocellular carcinoma is the second most common cause of
      cancer deaths. It remains challenging to intensify cancer treatment without
      impairing liver function. OBJECTIVE: The objective of the TheraSphere in the
      Treatment of Patients with Unresectable Hepatocellular Carcinoma (STOP-HCC) study
      is to examine the hypothesis that transarterial radioembolization (TheraSphere
      yttrium-90 glass microspheres) combined with standard first-line treatment with
      sorafenib will improve outcomes over treatment with sorafenib alone in
      unresectable hepatocellular carcinoma. The STOP-HCC study is the largest
      international, multicenter, prospective study of intra-arterial treatment in
      combination with sorafenib in unresectable hepatocellular carcinoma. Here we
      report the study design. METHODS: STOP-HCC is a prospective, phase 3, open-label,
      randomized controlled study conducted across up to 105 sites in North America,
      Europe, and Asia. Eligible adults have unresectable hepatocellular carcinoma and
      a life expectancy of at least 12 weeks, 1 or more unidimensional measurable
      lesions, Child-Pugh score 7 points or less, and Eastern Cooperative Oncology
      Group Performance Status score 1 or lower, and are candidates for treatment with
      sorafenib. Presence of branch portal vein tumor thrombosis is permitted. Patients
      were randomly assigned in a 1:1 ratio to receive either sorafenib alone or
      transarterial radioembolization followed by sorafenib within 2 to 6 weeks. The
      primary outcome is overall survival. Secondary outcomes are time to progression,
      time to untreatable progression, time to symptomatic progression, tumor response,
      quality of life, and adverse event occurrence. The study is an adaptive trial,
      comprising a group-sequential design with 2 interim analyses with 520 patients,
      and an option to increase the sample size to 700 patients at the second interim
      analysis. The sample size of 520 patients allows for 417 deaths to give 80% power
      to detect an increase in median overall survival from 10.7 months for the
      sorafenib group (based on the Sorafenib Hepatocellular Carcinoma Assessment
      Randomized Protocol [SHARP] trial) to 14.2 months for the transarterial
      radioembolization+sorafenib group (hazard ratio 0.754) with 2-sided alpha of .05.
      The increased sample size of 700 patients allows for 564 deaths to give 80% power
      to detect a smaller difference in median overall survival from 10.7 months for
      the sorafenib group to 13.7 months for the transarterial
      radioembolization+sorafenib group (hazard ratio 0.781). RESULTS: Enrollment for
      the study completed in September 2017. Results of the first and second interim
      analyses were reviewed by the Independent Data Monitoring Committee. The
      recommendation of the committee, at both interim analyses, was to continue the
      study without any changes. CONCLUSIONS: The STOP-HCC study will contribute toward
      the establishment of the role of combination therapy with transarterial
      radioembolization and sorafenib in the treatment of unresectable hepatocellular
      carcinoma with and without branch portal vein tumor thrombosis. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT01556490;
      https://clinicaltrials.gov/ct2/show/NCT01556490 (Archived by WebCite at
      http://www.webcitation.org/7188iygKs). REGISTERED REPORT IDENTIFIER: RR1
      10.2196/11234.

PMID- 30111529
TI  - The Modification of Vital Signs According to Nursing Students' Experiences
      Undergoing Cardiopulmonary Resuscitation Training via High-Fidelity Simulation:
      Quasi-Experimental Study.
AB  - BACKGROUND: High-fidelity simulation represents a primary tool in nursing
      education, especially when hands-on practical training is involved. OBJECTIVE: We
      sought to determine the influence of high-fidelity clinical simulation, applied
      during cardiopulmonary resuscitation (CPR) training, on blood pressure, heart
      rate, stress, and anxiety levels in 2 groups of nursing students. One group had
      experience in health contexts, whereas the other group had none. METHODS: We
      performed a quasi-experimental study. Data were collected between May and June
      2015 and included measurements of all the resting values, before and after
      participation in CPR clinical simulations regarding the 2 groups of university
      students (ie, with and without experience). RESULTS: An increase in vital signs
      was observed in students after participating in a clinical simulation scenario,
      especially the heart rate. In all students, increased stress and anxiety levels
      were observed before the first simulation case scenario. Also, in all study
      groups, a decrease in vital signs, stress levels, and anxiety was observed
      throughout the study. CONCLUSIONS: Participation in high-fidelity simulation
      experiences has both physiological and psychological effects on students.

PMID- 30111532
TI  - Louise Kenny: Obstetrician on a mission.

PMID- 30111530
TI  - Understanding Users' Vaping Experiences from Social Media: Initial Study Using
      Sentiment Opinion Summarization Techniques.
AB  - BACKGROUND: E-liquid is one of the main components in electronic nicotine
      delivery systems (ENDS). ENDS review comments could serve as an early warning on
      use patterns and even function to serve as an indicator of problems or adverse
      events pertaining to the use of specific e-liquids-much like types of responses
      tracked by the Food and Drug Administration (FDA) regarding medications.
      OBJECTIVE: This study aimed to understand users' "vaping" experience using
      sentiment opinion summarization techniques, which can help characterize how
      consumers think about specific e-liquids and their characteristics (eg, flavor,
      throat hit, and vapor production). METHODS: We collected e-liquid reviews on
      JuiceDB from June 27, 2013 to December 31, 2017 using its public application
      programming interface. The dataset contains 27,070 reviews for 8058 e-liquid
      products. Each review is accompanied by an overall rating and a set of 4 aspect
      ratings of an e-liquid, each on a scale of 1-5: flavor accuracy, throat hit,
      value, and cloud production. An iterative dichotomiser 3 (ID3)-based influential
      aspect analysis model was adopted to learn the key elements that impact e-liquid
      use. Then, fine-grained sentiment analysis was employed to mine opinions on
      various aspects of vaping experience related to e-liquids. RESULTS: We found that
      flavor accuracy and value were the two most important aspects that affected
      users' sentiments toward e-liquids. Of reviews in JuiceDB, 67.83% (18,362/27,070)
      were positive, while 12.67% (3430/27,070) were negative. This indicates that
      users generally hold positive attitudes toward e-liquids. Among the 9 flavors,
      fruity and sweet were the two most popular. Great and sweet tastes, reasonable
      value, and strong throat hit made users satisfied with fruity and sweet flavors,
      whereas "strange" tastes made users dislike those flavors. Meanwhile, users
      complained about some e-liquids' steep or expensive prices, bad quality, and
      harsh throat hit. There were 2342 fruity e-liquids and 2049 sweet e-liquids.
      There were 55.81% (1307/2342) and 59.83% (1226/2049) positive sentiments and
      13.62% (319/2342) and 12.88% (264/2049) negative sentiments toward fruity e
      liquids and sweet e-liquids, respectively. Great flavors and good vapors
      contributed to positive reviews of fruity and sweet products. However, bad tastes
      such as "sour" or "bitter" resulted in negative reviews. These findings can help
      businesses and policy makers to further improve product quality and formulate
      effective policy. CONCLUSIONS: This study provides an effective mechanism for
      analyzing users' ENDS vaping experience based on sentiment opinion summarization
      techniques. Sentiment opinions on aspect and products can be found using our
      method, which is of great importance to monitor e-liquid products and improve
      work efficiency.

PMID- 30111531
TI  - Virtual Medical Modality Implementation Strategies for Patient-Aligned Care Teams
      to Promote Veteran-Centered Care: Protocol for a Mixed-Methods Study.
AB  - BACKGROUND: The Veterans Health Administration (VHA) is making system-wide
      efforts to increase integrated use of health information technology (HIT),
      including My HealtheVet (MHV), the Veterans Affairs (VA) electronic patient
      portal, Vet Link kiosks, telehealth, and mobile apps. Integrated use of HIT can
      increase individual and system efficiency, maximize resources, and enhance
      patient outcomes. Prior research indicates that provider endorsement and
      reinforcement are key determinants of patient adoption of HIT. HIT implementation
      strategies need to reflect providers' perspectives to promote adoption and
      endorsement of these tools; however, providers often lack awareness or are
      unmotivated to incorporate HIT into clinical care with their patients. When these
      modalities are used by patients, the approach is often fragmented rather than
      integrated within and across care settings. Research is needed to identify
      effective implementation strategies for increasing patient-aligned care team
      (PACT) member (ie, the VHA's Patient Centered Medical Home) awareness and
      motivation to use HIT in a proactive and integrated approach with patients.
      OBJECTIVE: This paper describes the rationale, design, and methods of the PACT
      protocol to promote proactive integrated use of HIT. METHODS: In Aim 1, focus
      groups (n=21) were conducted with PACT members (n=65) along with questionnaires
      and follow-up individual interviews (n=16). In Aim 2, the team collaborated with
      VA clinicians, electronic health researchers and operational partners to conduct
      individual expert interviews (n=13), and an environmental scan to collect current
      and emerging provider-focused implementation tools and resources. Based on Aim 1
      findings, a gap analysis was conducted to determine what implementation
      strategies and content needed to be adapted or developed. Following the
      adaptation or development of resources, a PACT expert panel was convened to
      evaluate the resultant content. In Aim 3, a local implementation of PACT-focused
      strategies to promote integrated use of HIT was evaluated using pre- and
      postquestionnaire surveys, brief structured interviews, and secondary data
      analysis with PACT members (n=63). RESULTS: Study enrollment for Aim 1 has been
      completed. Aims 1 and 2 data collection and analysis are underway. Aim 3
      activities are scheduled for year 3. CONCLUSIONS: This work highlights the
      practical, technological, and participatory factors involved in facilitating
      implementation research designed to engage PACT clinical members in the proactive
      integrated use of HIT. These efforts are designed to support the integrated and
      proactive use of VA HIT to support clinical care coordination in ways that are
      directly aligned with PACT member preferences. This study evaluated integrated VA
      HIT use employing mixed-methods and multiple data sources. Deliverables included
      PACT-focused strategies to support integrated use of HIT in the ambulatory care
      setting that will also inform strategy development in other systems of care and
      support subsequent implementation efforts at regional and national levels.
      REGISTERED REPORT IDENTIFIER: RR1-10.2196/11262.

PMID- 30111534
TI  - Coupling between conformational dynamics and catalytic function at the active
      site of the lead-dependent ribozyme.
AB  - In common with other self-cleaving RNAs, the lead-dependent ribozyme (leadzyme)
      undergoes dynamic fluctuations to a chemically activated conformation. We
      explored the connection between conformational dynamics and self-cleavage
      function in the leadzyme using a combination of NMR spin-relaxation analysis of
      ribose groups and conformational restriction via chemical modification. The
      functional studies were performed with a North-methanocarbacytidine modification
      that prevents fluctuations to C2'-endo conformations while maintaining an intact
      2'-hydroxyl nucleophile. Spin-relaxation data demonstrate that the active-site
      Cyt-6 undergoes conformational exchange attributed to sampling of a minor C2'
      endo state with an exchange lifetime on the order of microseconds to tens of
      microseconds. A conformationally restricted species in which the fluctuations to
      the minor species are interrupted shows a drastic decrease in self-cleavage
      activity. Taken together, these data indicate that dynamic sampling of a minor
      species at the active site of this ribozyme, and likely of related naturally
      occurring motifs, is strongly coupled to catalytic function. The combination of
      NMR dynamics analysis with functional probing via conformational restriction is a
      general methodology for dissecting dynamics-function relationships in RNA.

PMID- 30111533
TI  - Macrophage-Derived Neuropilin-2 Exhibits Novel Tumor-Promoting Functions.
AB  - Tumor-associated macrophages (TAM) are causally associated with tumorigenesis as
      well as regulation of antitumor immune responses and have emerged as potential
      immunotherapeutic targets. Recent evidence suggests TAM phagocytose apoptotic
      tumor cells within the tumor microenvironment through efferocytosis in an
      immunologically silent manner, thus maintaining an immunosuppressed
      microenvironment. The signal transduction pathways coupling efferocytosis and
      immunosuppression are not well known. Neuropilin-2 (NRP2) is a member of the
      membrane-associated neuropilin family and has been reported in different immune
      cells but is poorly characterized. In this study, we show that NRP2 is expressed
      during macrophage differentiation, is induced by tumor cells, and regulates
      phagocytosis in macrophages. Furthermore, NRP2 in TAM promoted efferocytosis and
      facilitated tumor growth. Deletion of NRP2 from TAM impaired the clearance of
      apoptotic tumor cells and increased secondary necrosis within tumors. This
      resulted in a break in the immune tolerance and reinitiated antitumor immune
      responses, characterized by robust infiltration of CD8+ T and natural killer
      cells. This result suggests NRP2 may act as a molecular mediator that connects
      efferocytosis and immune suppression. Deletion of NRP2 in TAM downregulated
      several immunosuppressive and tumor-promoting genes and upregulated
      immunostimulatory genes in the myeloid compartment. Taken together, our study
      demonstrates that TAM-derived NRP2 plays a crucial role in tumor promotion
      through efferocytosis, opening the enticing option for the development of
      effective immunotherapy targeting TAM.Significance: Neuropilin-2 in macrophages
      promotes tumor growth by regulating efferocytosis of apoptotic tumor cells and
      orchestrating immune suppression.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/19/5600/F1.large.jpg Cancer
      Res; 78(19); 5600-17. (c)2018 AACR.

PMID- 30111535
TI  - Molecular mechanism of substrate recognition and specificity of tRNAHis
      guanylyltransferase during nucleotide addition in the 3'-5' direction.
AB  - The tRNAHis guanylyltransferase (Thg1) transfers a guanosine triphosphate (GTP)
      in the 3'-5' direction onto the 5'-terminal of tRNAHis, opposite adenosine at
      position 73 (A73). The guanosine at the -1 position (G-1) serves as an identity
      element for histidyl-tRNA synthetase. To investigate the mechanism of recognition
      for the insertion of GTP opposite A73, first we constructed a two-stranded
      tRNAHis molecule composed of a primer and a template strand through division at
      the D-loop. Next, we evaluated the structural requirements of the incoming GTP
      from the incorporation efficiencies of GTP analogs into the two-piece tRNAHis
      Nitrogen at position 7 and the 6-keto oxygen of the guanine base were important
      for G-1 addition; however, interestingly, the 2-amino group was found not to be
      essential from the highest incorporation efficiency of inosine triphosphate.
      Furthermore, substitution of the conserved A73 in tRNAHis revealed that the G-1
      addition reaction was more efficient onto the template containing the opposite
      A73 than onto the template with cytidine (C73) or other bases forming canonical
      Watson-Crick base-pairing. Some interaction might occur between incoming GTP and
      A73, which plays a role in the prevention of continuous templated 3'-5'
      polymerization. This study provides important insights into the mechanism of
      accurate tRNAHis maturation.

PMID- 30111536
TI  - DCAF13 promotes pluripotency by negatively regulating SUV39H1 stability during
      early embryonic development.
AB  - Mammalian oocytes and zygotes have the unique ability to reprogram a somatic cell
      nucleus into a totipotent state. SUV39H1/2-mediated histone H3 lysine-9
      trimethylation (H3K9me3) is a major barrier to efficient reprogramming. How
      SUV39H1/2 activities are regulated in early embryos and during generation of
      induced pluripotent stem cells (iPSCs) remains unclear. Since expression of the
      CRL4 E3 ubiquitin ligase in oocytes is crucial for female fertility, we analyzed
      putative CRL4 adaptors (DCAFs) and identified DCAF13 as a novel CRL4 adaptor that
      is essential for preimplantation embryonic development. Dcaf13 is expressed from
      eight-cell to morula stages in both murine and human embryos, and Dcaf13 knockout
      in mice causes preimplantation-stage mortality. Dcaf13 knockout embryos are
      arrested at the eight- to sixteen-cell stage before compaction, and this arrest
      is accompanied by high levels of H3K9me3. Mechanistically, CRL4-DCAF13 targets
      SUV39H1 for polyubiquitination and proteasomal degradation and therefore
      facilitates H3K9me3 removal and zygotic gene expression. Taken together, CRL4
      DCAF13-mediated SUV39H1 degradation is an essential step for progressive genome
      reprogramming during preimplantation embryonic development.

PMID- 30111538
TI  - Cellular function given parametric variation in the Hodgkin and Huxley model of
      excitability.
AB  - How is reliable physiological function maintained in cells despite considerable
      variability in the values of key parameters of multiple interacting processes
      that govern that function? Here, we use the classic Hodgkin-Huxley formulation of
      the squid giant axon action potential to propose a possible approach to this
      problem. Although the full Hodgkin-Huxley model is very sensitive to fluctuations
      that independently occur in its many parameters, the outcome is in fact
      determined by simple combinations of these parameters along two physiological
      dimensions: structural and kinetic (denoted S and K, respectively). Structural
      parameters describe the properties of the cell, including its capacitance and the
      densities of its ion channels. Kinetic parameters are those that describe the
      opening and closing of the voltage-dependent conductances. The impacts of
      parametric fluctuations on the dynamics of the system-seemingly complex in the
      high-dimensional representation of the Hodgkin-Huxley model-are tractable when
      examined within the S-K plane. We demonstrate that slow inactivation, a
      ubiquitous activity-dependent feature of ionic channels, is a powerful local
      homeostatic control mechanism that stabilizes excitability amid changes in
      structural and kinetic parameters.

PMID- 30111537
TI  - Error-free DNA damage tolerance pathway is facilitated by the Irc5 translocase
      through cohesin.
AB  - DNA damage tolerance (DDT) mechanisms facilitate replication resumption and
      completion when DNA replication is blocked by bulky DNA lesions. In budding
      yeast, template switching (TS) via the Rad18/Rad5 pathway is a favored DDT
      pathway that involves usage of the sister chromatid as a template to bypass DNA
      lesions in an error-free recombination-like process. Here, we establish that the
      Snf2 family translocase Irc5 is a novel factor that promotes TS and averts single
      stranded DNA persistence during replication. We demonstrate that, during
      replication stress, Irc5 enables replication progression by assisting enrichment
      of cohesin complexes, recruited in an Scc2/Scc4-dependent fashion, near blocked
      replication forks. This allows efficient formation of sister chromatid junctions
      that are crucial for error-free DNA lesion bypass. Our results support the notion
      of a key role of cohesin in the completion of DNA synthesis under replication
      stress and reveal that the Rad18/Rad5-mediated DDT pathway is linked to cohesin
      enrichment at sites of perturbed replication via the Snf2 family translocase
      Irc5.

PMID- 30111542
TI  - Knowledge infrastructure and safe operating spaces in social-ecological systems.
AB  - Maintaining safe operating spaces for exploited natural systems in the face of
      uncertainty is a key sustainability challenge. This challenge can be viewed as a
      problem in which human society must navigate in a limited space of acceptable
      futures in which humans enjoy sufficient well-being and avoid crossing planetary
      boundaries. A critical obstacle is the nature of society as a controller with
      endogenous dynamics affected by knowledge, values, and decision-making fallacies.
      We outline an approach for analyzing the role of knowledge infrastructure in
      maintaining safe operating spaces. Using a classic natural resource problem as an
      illustration, we find that a small safe operating space exists that is
      insensitive to the type of policy implementation, while in general, a larger safe
      operating space exists which is dependent on the implementation of the "right"
      policy. Our analysis suggests the importance of considering societal response
      dynamics to varying policy instruments in defining the shape of safe operating
      spaces.

PMID- 30111541
TI  - Self-organized criticality and pattern emergence through the lens of tropical
      geometry.
AB  - Tropical geometry, an established field in pure mathematics, is a place where
      string theory, mirror symmetry, computational algebra, auction theory, and so
      forth meet and influence one another. In this paper, we report on our discovery
      of a tropical model with self-organized criticality (SOC) behavior. Our model is
      continuous, in contrast to all known models of SOC, and is a certain scaling
      limit of the sandpile model, the first and archetypical model of SOC. We describe
      how our model is related to pattern formation and proportional growth phenomena
      and discuss the dichotomy between continuous and discrete models in several
      contexts. Our aim in this context is to present an idealized tropical toy model
      (cf. Turing reaction-diffusion model), requiring further investigation.

PMID- 30111540
TI  - General methodology for inferring failure-spreading dynamics in networks.
AB  - A generic modeling framework to infer the failure-spreading process based on
      failure times of individual nodes is proposed and tested in four simulation
      studies: one for cascading failures in interdependent power and transportation
      networks, one for influenza epidemics, one benchmark test case for congestion
      cascade in a transportation network, and one benchmark test case for cascading
      power outages. Four general failure-spreading mechanisms-external, temporal,
      spatial, and functional-are quantified to capture what drives the spreading of
      failures. With the failure time of each node given, the proposed methodology
      demonstrates remarkable capability of inferring the underlying general failure
      spreading mechanisms and accurately reconstructing the failure-spreading process
      in all four simulation studies. The analysis of the two benchmark test cases also
      reveals the robustness of the proposed methodology: It is shown that a failure
      spreading process embedded by specific failure-spreading mechanisms such as flow
      redistribution can be captured with low uncertainty by our model. The proposed
      methodology thereby presents a promising channel for providing a generally
      applicable framework for modeling, understanding, and controlling failure
      spreading in a variety of systems.

PMID- 30111539
TI  - Control of the Restriction Point by Rb and p21.
AB  - The Restriction Point was originally defined as the moment that cells commit to
      the cell cycle and was later suggested to coincide with hyperphosphorylation of
      the retinoblastoma protein (Rb). Current cell cycle models posit that cells exit
      mitosis into a pre-Restriction Point state, where they have low cyclin-dependent
      kinase (CDK) activity and hypophosphorylated Rb; passage through the Restriction
      Point then occurs in late G1. Recent single-cell studies have challenged the
      current paradigm, raising questions about the location of the Restriction Point
      and the notion that cells exit mitosis into a pre-Restriction Point state. Here,
      we use a variety of single-cell techniques to show that both noncancer and cancer
      cells bifurcate into two subpopulations after anaphase, marked by increasing vs.
      low CDK2 activity and hyper- vs. hypophosphorylation of Rb. Notably,
      subpopulations with hyper- and hypophosphorylated Rb are present within minutes
      after anaphase, delineating one subpopulation that never "uncrosses" the
      Restriction Point and continues cycling and another subpopulation that exits
      mitosis into an uncommitted pre-Restriction Point state. We further show that the
      CDK inhibitor p21 begins rising in G2 in mother cells whose daughters exit
      mitosis into the pre-Restriction Point, CDK2low state. Furthermore, degradation
      of p21 coincides with escape from the CDK2low state and passage through the
      Restriction Point. Together, these data support a model in which only a subset of
      cells returns to a pre-Restriction Point state after mitosis and where the
      Restriction Point is sensitive to not only mitogens, but also inherited DNA
      replication stress via p21.

PMID- 30111543
TI  - N-glycan microheterogeneity regulates interactions of plasma proteins.
AB  - Altered glycosylation patterns of plasma proteins are associated with autoimmune
      disorders and pathogenesis of various cancers. Elucidating glycoprotein
      microheterogeneity and relating subtle changes in the glycan structural
      repertoire to changes in protein-protein, or protein-small molecule interactions,
      remains a significant challenge in glycobiology. Here, we apply mass spectrometry
      based approaches to elucidate the global and site-specific microheterogeneity of
      two plasma proteins: alpha1-acid glycoprotein (AGP) and haptoglobin (Hp). We then
      determine the dissociation constants of the anticoagulant warfarin to different
      AGP glycoforms and reveal how subtle N-glycan differences, namely, increased
      antennae branching and terminal fucosylation, reduce drug-binding affinity.
      Conversely, similar analysis of the haptoglobin-hemoglobin (Hp-Hb) complex
      reveals the contrary effects of fucosylation and N-glycan branching on Hp-Hb
      interactions. Taken together, our results not only elucidate how glycoprotein
      microheterogeneity regulates protein-drug/protein interactions but also inform
      the pharmacokinetics of plasma proteins, many of which are drug targets, and
      whose glycosylation status changes in various disease states.

PMID- 30111546
TI  - Where's the leadership? Future commitments of Unicef and WHO for global child
      health.

PMID- 30111545
TI  - Coupling integrin dynamics to cellular adhesion behaviors.
AB  - Visualizing fluorescent proteins is essential for understanding cellular
      function. While advances in microscopy can now resolve individual molecules,
      determining whether the labeled molecules report native behaviors and how the
      measured behaviors can be coupled to cellular outputs remains challenging. Here,
      we used integrin alpha-beta heterodimers - which connect extracellular matrix
      (ECM) and the cytoskeleton - to quantify the mobility and conformation of labeled
      integrins. We found that while unlabeled and labeled integrins all localized to
      adhesions and support anchorage-dependent cell function, integrin mobility
      decreased when the beta rather than the alpha subunit was labeled. In contrast to
      unlabeled and alpha labeled subunits, beta labeled subunits changed cellular
      behavior; decreasing protrusive activity and increasing adhesion size and the
      extent of cell spreading. Labeling the beta subunit changed the integrin
      conformation, extending the molecule and exposing an epitope that is revealed by
      activation with Mn2+ treatment. Our findings indicate labeling induced changes in
      dynamic integrin behavior alter molecular conformation as well as cellular
      adhesion-dependent function to demonstrate a coupling between molecular inputs
      and distinct cellular outputs.This article has an associated First Person
      interview with the first author of the paper.

PMID- 30111547
TI  - Ethical criteria for developing medical interventions in a for-profit world.

PMID- 30111548
TI  - Level of residual enzyme activity modulates the phenotype in phosphoglycerate
      kinase deficiency.
AB  - OBJECTIVE: To study the variable clinical picture and exercise tolerance of
      patients with phosphoglycerate kinase (PGK) 1 deficiency and how it relates to
      residual PGK enzyme activity. METHODS: In this case series study, we evaluated 7
      boys and men from 5 families with PGK1 deficiency. Five had pure muscle symptoms,
      while 2 also had mild intellectual disability with or without anemia. Muscle
      glycolytic and oxidative capacities were evaluated by an ischemic forearm
      exercise test and by cycle ergometry. RESULTS: Enzyme levels of PGK were 4% to 9%
      of normal in red cells and 5% to10% in muscle in pure myopathy patients and 2.6%
      in both muscle and red cells in the 2 patients with multisystem involvement.
      Patients with pure myopathy had greater increases in lactate with ischemic
      exercise (2-3 mmol/L) vs the 2 multisystem-affected patients (<1 mmol/L).
      Myopathy patients had higher oxidative capacity in cycle exercise vs multisystem
      affected patients (~30 vs ~15 mL/kg per minute). One multisystem-affected patient
      developed frank myoglobinuria after the short exercise test. CONCLUSIONS: This
      case series study of PGK1 deficiency suggests that the level of impaired
      glycolysis in PGK deficiency is a major determinant of phenotype. Lower
      glycolytic capacity in PGK1 deficiency seems to result in multisystem involvement
      and increased susceptibility to exertional rhabdomyolysis.

PMID- 30111549
TI  - Deep brain stimulation improves restless legs syndrome in patients with Parkinson
      disease.
AB  - OBJECTIVE: To study the effect of subthalamic nucleus (STN) deep brain
      stimulation (DBS) in patients with Parkinson disease (PD) and moderate to severe
      restless legs syndrome (RLS) on their RLS symptoms. METHODS: Patients undergoing
      STN DBS surgery for PD completed the International RLS Study Group Rating Scale
      (IRLS) and RLS Quality of Life (QoL) questionnaires preoperatively and
      postoperatively at 6 months, 1 year, and 2 years. The primary outcome measure was
      IRLS sum score and subscales (severity and impact) and the secondary measure was
      RLS QoL scores. Differences among the mean scores over time were analyzed using
      mixed model regression. RESULTS: Twenty-two patients were enrolled. The
      preoperative IRLS sum scores were 19.59 +/- 6.95, severity subscale 12.91 +/-
      4.33, impact subscale 4.45 +/- 2.72, and transformed RLS QoL score 68.30 +/-
      20.26. The differences between preoperative and averaged postoperative scores
      were IRLS sum score -7.80, severity subscale -5.50, impact subscale -1.20, and
      RLS QoL 4.73. The overall F tests demonstrated differences among the times for
      the means of the IRLS sum and subscales: p < 0.05. There were no correlations
      between RLS symptoms improvement and PD motor symptoms improvement or reduction
      in PD medications. Half of the patients had at least 50% improvement and 27% had
      resolution of their RLS symptoms (IRLS = 0). CONCLUSIONS: STN DBS significantly
      decreased RLS symptoms in patients with PD despite a decrease in dopaminergic
      treatment. This improvement was sustained over a 2-year period. CLASSIFICATION OF
      EVIDENCE: This study provides Class IV evidence that for patients with PD and
      moderate to severe RLS, STN DBS improves RLS symptoms.

PMID- 30111544
TI  - Rev7 dimerization is important for assembly and function of the Rev1/Polzeta
      translesion synthesis complex.
AB  - The translesion synthesis (TLS) polymerases Polzeta and Rev1 form a complex that
      enables replication of damaged DNA. The Rev7 subunit of Polzeta, which is a
      multifaceted HORMA (Hop1, Rev7, Mad2) protein with roles in TLS, DNA repair, and
      cell-cycle control, facilitates assembly of this complex by binding Rev1 and the
      catalytic subunit of Polzeta, Rev3. Rev7 interacts with Rev3 by a mechanism
      conserved among HORMA proteins, whereby an open-to-closed transition locks the
      ligand underneath the "safety belt" loop. Dimerization of HORMA proteins promotes
      binding and release of this ligand, as exemplified by the Rev7 homolog, Mad2.
      Here, we investigate the dimerization of Rev7 when bound to the two Rev7-binding
      motifs (RBMs) in Rev3 by combining in vitro analyses of Rev7 structure and
      interactions with a functional assay in a Rev7-/- cell line. We demonstrate that
      Rev7 uses the conventional HORMA dimerization interface both to form a homodimer
      when tethered by the two RBMs in Rev3 and to heterodimerize with other HORMA
      domains, Mad2 and p31comet Structurally, the Rev7 dimer can bind only one copy of
      Rev1, revealing an unexpected Rev1/Polzeta architecture. In cells, mutation of
      the Rev7 dimer interface increases sensitivity to DNA damage. These results
      provide insights into the structure of the Rev1/Polzeta TLS assembly and
      highlight the function of Rev7 homo- and heterodimerization.

PMID- 30111551
TI  - The search for Parkinson disease biomarkers: Retinal thinning as a correlate of
      dopamine loss.

PMID- 30111550
TI  - Retinal thinning associates with nigral dopaminergic loss in de novo Parkinson
      disease.
AB  - OBJECTIVE: To analyze the relationship between retinal thinning and nigral
      dopaminergic loss in de novo Parkinson disease (PD). METHODS: Forty-nine patients
      with PD and 54 age-matched controls were analyzed. Ophthalmologic examination and
      macula optical coherence tomography scans were performed with additional
      microperimetry, N-(3-[18F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl)
      nortropane PET, and 3T MRI scans were done in patients with PD only. Retinal
      layer thickness and volume were measured in subfields of the 1-, 2.22-, and 3.45
      mm Early Treatment of Diabetic Retinopathy Study circle and compared in patients
      with PD and controls. Correlation of inner retinal layer thinning with
      microperimetric response was examined in patients with PD, and the relationships
      between retinal layer thickness and dopamine transporter densities in the
      ipsilateral caudate, anterior and posterior putamen, and substantia nigra were
      analyzed. RESULTS: Retinal layer thinning was observed in the temporal and
      inferior 2.22-mm sectors (false discovery rate-adjusted p < 0.05) of drug-naive
      patients with PD, particularly the inner plexiform and ganglion cell layers. The
      thickness of these layers in the inferior 2.22-mm sector showed a negative
      correlation with the Hoehn and Yahr stage (p = 0.032 and 0.014, respectively).
      There was positive correlation between macular sensitivity and retinal layer
      thickness in all 3.45-mm sectors, the superior 2.22-mm sector, and 1-mm circle (p
      < 0.05 for all). There was an association between retinal thinning and
      dopaminergic loss in the left substantia nigra (false discovery rate-adjusted p <
      0.001). CONCLUSION: Retinal thinning is present in the early stages of PD,
      correlates with disease severity, and may be linked to nigral dopaminergic
      degeneration. Retinal imaging may be useful for detection of pathologic changes
      occurring in early PD.

PMID- 30111552
TI  - Sociodemographic Factors and Survival of Infants With Congenital Heart Defects.
AB  - OBJECTIVES: To examine the first-year survival of infants with congenital heart
      defects (CHDs) and investigate the potential role of socioeconomic and
      demographic factors on survival. METHODS: Subjects included 15 533 infants with
      CHDs born between 2004 and 2013 ascertained by the NC Birth Defects Monitoring
      Program. We classified CHDs into the following 3 groups: critical univentricular
      (n = 575), critical biventricular (n = 1494), and noncritical biventricular (n =
      13 345). We determined vital status and age at death through linkage to state
      vital records and used geocoded maternal residence at birth to obtain census
      information for study subjects. We calculated Kaplan-Meier survival estimates by
      maternal and infant characteristics and derived hazard ratios from Cox
      proportional hazard models for selected exposures. RESULTS: Among all infants
      with CHDs, there were 1289 deaths (8.3%) in the first year. Among infants with
      univentricular defects, 61.6% (95% confidence interval [CI]: 57.7%-65.7%)
      survived. Survival among infants with univentricular defects was considerably
      better for those whose fathers were >=35 years old (71.6%; 95% CI: 63.8%-80.3%)
      compared with those whose fathers were younger (59.7%; 95% CI: 54.6%-65.2%).
      Factors associated with survival among infants with any biventricular defect
      included maternal education, race and/or ethnicity, marital status, and delivery
      at a heart center. The hazard of infant mortality was greatest among non-Hispanic
      African American mothers. CONCLUSIONS: Survival among infants with critical
      univentricular CHDs was less variable across sociodemographic categories compared
      with survival among infants with biventricular CHDs. Sociodemographic differences
      in survival among infants with less severe CHDs reinforces the importance of
      ensuring culturally effective pediatric care for at-risk infants and their
      families.

PMID- 30111553
TI  - Treatment of Ventricular Fibrillation Due to Ammonium Bifluoride Poisoning With
      Hemodialysis.
AB  - Ammonium bifluoride is an inorganic, fluoride-containing compound found in glass
      and metal etching products, as well as wheel cleaners. Fluoride toxicity is a
      common cause of preventable poisoning and has been reported to cause life
      threatening ventricular dysrhythmias. Here, we report a case of recurrent
      ventricular fibrillation secondary to ingestion of ammonium bifluoride. The
      patient presented with vomiting and coma. She was intubated for altered mental
      status and respiratory failure and subsequently had 5 episodes of ventricular
      fibrillation, each resolving with a single defibrillation. She developed
      metabolic acidosis and hypocalcemia, which were treated with sodium bicarbonate
      and calcium gluconate, respectively. During transfer to a tertiary care
      children's hospital, ventricular fibrillation recurred despite electrolyte
      correction. Hemodialysis (HD) was initiated emergently. No further dysrhythmia
      occurred after initiation of HD. The result of a basic urine drug screen was
      negative, and a comprehensive drug screen (gas chromatography and mass
      spectroscopy) revealed only a nonsignificant peak for diphenhydramine. Subsequent
      laboratory evaluation revealed an elevated serum fluoride level. Diagnostic
      laryngoscopy and upper endoscopy did not reveal evidence of caustic injury. She
      was successfully extubated on hospital day 2 and discharged from the hospital on
      day 4 with no neurologic sequelae. With this example, we demonstrate a potential
      therapeutic approach to this potentially lethal poisoning. Fluoride toxicity is
      typically treated with calcium. However, dysrhythmia may result from calcium
      independent direct myocardial toxicity. The kinetics of fluoride are amenable to
      HD, and renal clearance is slow. The potential use of HD in cases of fluoride
      poisoning refractory to other therapies warrants further study.

PMID- 30111554
TI  - Changes in midlife death rates across racial and ethnic groups in the United
      States: systematic analysis of vital statistics.
AB  - OBJECTIVE: To systematically compare midlife mortality patterns in the United
      States across racial and ethnic groups during 1999-2016, documenting causes of
      death and their relative contribution to excess deaths. DESIGN: Trend analysis of
      US vital statistics among racial and ethnic groups. SETTING: United States, 1999
      2016. POPULATION: US adults aged 25-64 years (midlife). MAIN OUTCOME MEASURES:
      Absolute changes in mortality measured as average year-to-year change during 1999
      2016 and 2012-16; excess deaths attributable to increasing mortality; and
      relative changes in mortality measured as relative difference between mortality
      in 1999 versus 2016 and the nadir year versus 2016, and the slope of modeled
      mortality trends for 1999-2016 and for intervals between joinpoints. RESULTS:
      During 1999-2016, all cause mortality in midlife increased not only among non
      Hispanic (NH) whites but also among NH American Indians and Alaskan Natives.
      Although all cause mortality initially decreased among NH blacks, Hispanics, and
      NH Asians and Pacific Islanders, this trend ended in 2009-11. Drug overdoses were
      the leading cause of increased mortality in midlife in each population, but
      mortality also increased for alcohol related conditions, suicides, and organ
      diseases involving multiple body systems. Although midlife mortality among NH
      whites increased across a multitude of conditions, a similar trend affected non
      white populations. Absolute (year-to-year) increases in midlife mortality among
      non-white populationsoften matched or exceeded those of NH whites, especially in
      2012-16, when the rate of increase intensified for many causes of death. During
      1999-2016, NH American Indians and Alaskan Natives experienced large increases in
      midlife mortality from 12 causes, not only drug overdoses (411.4%) but also
      hypertensive diseases (269.3%), liver cancer (115.1%), viral hepatitis (112.1%),
      and diseases of the nervous system (99.8%). NH blacks experienced increased
      midlife mortality from 17 causes, including drug overdoses (149.6%), homicides
      (21.4%), hypertensive diseases (15.5%), obesity (120.7%), and liver cancer
      (49.5%). NH blacks also experienced retrogression: after a period of stable or
      declining midlife mortality early in 1999-2016, death rates increased for alcohol
      related liver disease, chronic lower respiratory tract disease, suicides,
      diabetes, and pancreatic cancer. Among Hispanics, midlife mortality increased
      across 12 causes, including drug overdoses (80.0%), hypertensive diseases
      (40.6%), liver cancer (41.8%), suicides (21.9%), obesity (106.6%), and metabolic
      disorders (60.0%). Retrogression also occurred in this population; after a period
      of declining mortality, death rates increased for alcohol related liver disease,
      mental and behavioral disorders involving psychoactive substances, and homicides.
      NH Asians and Pacific Islanders were least affected by this trend but also
      experienced increases in midlife mortality from drug overdoses (300.6%), alcohol
      related liver disease (62.9%), hypertensive diseases (28.3%), and brain cancer
      (56.6%). The suicide rate in this group increased by 29.7% after 2001. The
      relative increase in US midlife mortality differed by sex and geography. For
      example, the relative increase in fatal drug overdoses was greater among women
      than among men. Although the relative increase in midlife mortality was generally
      greater in non-metropolitan (ie, rural) areas, the relative increase in drug
      overdoses among NH whites and Hispanics was greatest in suburban fringe areas of
      large cities, and among NH blacks was greatest in small cities. CONCLUSIONS:
      Mortality in midlife in the US has increased across racial-ethnic populations for
      a variety of conditions, especially in recent years, offsetting years of progress
      in lowering mortality rates. This reversal carries added consequences for racial
      groups with high baseline mortality rates, such as for NH blacks and NH American
      Indians and Alaskan Natives. That death rates are increasing throughout the US
      population for dozens of conditions signals a systemic cause and warrants prompt
      action by policy makers to tackle the factors responsible for declining health in
      the US.

PMID- 30111555
TI  - Channeling vorticity: modeling the filter-feeding mechanism in silver carp using
      MUCT and 3D PIV.
AB  - Invasive silver carp are thriving within eutrophic environments in the United
      States, in part because of their highly efficient filter-feeding mechanism.
      Silver carp utilize modified gill rakers to capture a specific range of food;
      however, their greatly modified filtering morphology allows them to feed on
      phytoplankton and zooplankton ranging in size from 4 to 85 um. The filtering
      apparatus of silver carp comprises rigid filtering plates where the outer anatomy
      of these plates is characterized by long parallel channels that change in
      orientation along the length of the plate. Here, we investigate the underlying
      morphology and concomitant hydrodynamics that support the filtration mechanisms
      of silver and bighead carp. Bighead carp are also invasive filter feeders, but
      their filtering apparatus is morphologically distinct from that of silver carp.
      Using 3D particle image velocimetry, we determined how particles and fluid
      interact with the surface of the gill rakers/plates. Filtering plates in silver
      carp induce strong directed vortical flow, whereas the filtering apparatus of
      bighead carp resulted in a type of haphazard cross-flow filtration. The organized
      vortical flow established by silver carp likely increased the number of
      interactions that the particle-filled water had with the filtering membrane. This
      strong vortical organization is maintained only at 0.75 body lengths s-1, and
      vortical flow is poorly developed and maintained at slower and faster speeds.
      Moreover, we found that absolute vorticity magnitude in silver carp is an order
      of magnitude greater than in bighead carp.

PMID- 30111556
TI  - Do squid breathe through their skin?
AB  - Squid are thought to obtain a large portion of their oxygen via simple diffusion
      across the skin in addition to uptake at the gills. Although this hypothesis has
      support from indirect evidence and is widely accepted, no empirical examinations
      have been conducted to assess the validity of this hypothesis. In this study, we
      examined cutaneous respiration in two squid species, Doryteuthis pealeii and
      Lolliguncula brevis, using a divided chamber to physically separate the mantle
      cavity and gills from the outer mantle surface. We measured oxygen consumption
      and ammonia excretion rates in the two compartments and found that, at rest,
      squid only obtain enough oxygen cutaneously to meet the demand of the skin tissue
      locally (12% of total) and excrete little ammonia across the skin. The majority
      of oxygen is obtained via the traditional branchial pathway. In light of these
      findings, we re-examine and discuss the indirect evidence that has supported the
      cutaneous respiration hypothesis.

PMID- 30111558
TI  - Wing inertia as a cause of aerodynamically uneconomical flight with high angles
      of attack in hovering insects.
AB  - Flying insects can maintain maneuverability in the air by flapping their wings,
      and, to save energy, the wings should operate following optimal kinematics.
      However, unlike conventional rotary wings, insects operate their wings at
      aerodynamically uneconomical and high angles of attack (AoA). Although insects
      have continuously received attention from biologists and aerodynamicists, the
      high AoA operation in insect flight has not been clearly explained. Here, we used
      a theoretical blade-element model to examine the impact of wing inertia on the
      power requirement and flapping AoA, based on 3D free-hovering flight wing
      kinematics of a horned beetle, Allomyrina dichotoma The relative simplicity of
      the model allowed us to search for the best AoA distributed along the wingspan,
      which generate the highest vertical force per unit power. We show that, although
      elastic elements may be involved in flight muscles to store and save energy, the
      insect still has to use substantial power to accelerate its wings, because
      inertial energy stores should be used to overcome aerodynamic drag before being
      stored elastically. At the same flapping speed, a wing operating at a higher AoA
      requires lower inertial torque, and therefore lower inertial power output, at
      stroke reversals than a wing operating at an aerodynamically optimal low AoA. An
      interactive aerodynamic-inertial effect thereby enables the wing to flap at
      sufficiently high AoA, which causes an aerodynamically uneconomical flight in an
      effort to minimize the net flight energy.

PMID- 30111557
TI  - Corticosterone implants produce stress-hyporesponsive birds.
AB  - In birds, the use of corticosterone (Cort) implants is a frequent tool aimed at
      simulating systemic elevations of this hormone and studying effects on biological
      traits (e.g. physiology, morphology, behavior). This manipulation may alter
      adrenocortical function, potentially changing both baseline (CortBAS) and stress
      induced (CortSTRESS) plasma Cort levels. However, implant effects on the latter
      trait are rarely measured, disregarding downstream consequences of potentially
      altered stress responses. Here, we analyzed the effects of Cort implants on both
      CortBAS and CortSTRESS in nestling and adult European white storks, Ciconia
      ciconia In addition, we performed a review of 50 studies using Cort implants in
      birds during the last two decades to contextualize stork results, assess
      researchers' patterns of use and infer current study biases. High and low doses
      of Cort implants resulted in a decrease of both CortBAS (31-71% below controls)
      and CortSTRESS (63-79% below controls) in storks. Our literature review revealed
      that CortBAS generally increases (72% of experiments) whereas CortSTRESS
      decreases (78% of experiments) following implant treatment in birds. Our results
      challenge and expand the prevailing assumption that Cort implants increase
      circulating CortBAS levels because: (i) CortBAS levels show a quadratic
      association with implant dose across bird species, and decreased levels may occur
      at both high and low implant doses, and (ii) Cort implants also decrease
      CortSTRESS levels, thus producing stress-hyporesponsive phenotypes. It is time to
      work towards a better understanding of the effects of Cort implants on
      adrenocortical function, before addressing downstream links to variation in other
      biological traits.

PMID- 30111559
TI  - Ocean acidification does not limit squid metabolism via blood oxygen supply.
AB  - Ocean acidification is hypothesized to limit the performance of squid owing to
      their exceptional oxygen demand and pH sensitivity of blood-oxygen binding, which
      may reduce oxygen supply in acidified waters. The critical oxygen partial
      pressure (P crit), the P O2  below which oxygen supply cannot match basal demand,
      is a commonly reported index of hypoxia tolerance. Any CO2-induced reduction in
      oxygen supply should be apparent as an increase in P crit In this study, we
      assessed the effects of CO2 (46-143 Pa; 455-1410 MUatm) on the metabolic rate and
      P crit of two squid species - Dosidicus gigas and Doryteuthis pealeii - through
      manipulative experiments. We also developed a model, with inputs for hemocyanin
      pH sensitivity, blood P CO2  and buffering capacity, that simulates blood oxygen
      supply under varying seawater CO2 partial pressures. We compare model outputs
      with measured P crit in squid. Using blood-O2 parameters from the literature for
      model inputs, we estimated that, in the absence of blood acid-base regulation, an
      increase in seawater P CO2  to 100 Pa (~1000 MUatm) would result in a maximum
      drop in arterial hemocyanin-O2 saturation by 1.6% at normoxia and a P crit
      increase of ~0.5 kPa. Our live-animal experiments support this supposition, as
      CO2 had no effect on measured metabolic rate or P crit in either squid species.

PMID- 30111560
TI  - The 5' Untranslated Region of Human Bocavirus Capsid Transcripts Regulates Viral
      mRNA Biogenesis and Alternative Translation.
AB  - The capsid mRNA transcripts of human bocavirus 1 (HBoV1) can be generated by
      alternative splicing from the mRNA precursor transcribed from the P5 promoter.
      However, the alternative translation regulation mechanism of capsid mRNA
      transcripts is largely unknown. Here we report that the polycistronic capsid mRNA
      transcripts encode VP1, VP2, and VP3 in vitro and in vivo The 5' untranslated
      regions (UTRs) of capsid mRNA transcripts, which consist of exons, affected not
      only the abundance of mRNA but also the translation pattern of capsid proteins.
      Further study showed that exons 2 and 3 were critical for the abundance of mRNA,
      while exon 4 regulated capsid translation. Alternative translation of capsid mRNA
      involved a leaky scan mechanism. Mutating the upstream ATGs (uATGs) located in
      exon 4 resulted in more mRNA transcripts polyadenylated at the proximal
      polyadenylation [(pA)p] site, leading to increased capsid mRNA transcripts.
      Moreover, uATG mutations induced more VP1 expression, while VP3 expression was
      decreased, which resulted in less progeny virus production. Our data show that
      the 5' UTR of HBoV1 plays a critical role in the modulation of mRNA abundance,
      alternative RNA processing, alternative translation, and progeny virus
      production.IMPORTANCE Alternative translation of HBoV1 capsid mRNAs is vital for
      the viral life cycle, as capsid proteins perform essential functions in genome
      packaging, assembly, and antigenicity. The 5' untranslated regions (UTRs) of
      capsid mRNAs are generated by alternative splicing, and they contain different
      exons. Our study shows that the 5' UTR not only modulates mRNA abundance but also
      regulates capsid expression. Two upstream ATGs (uATGs) that were upstream of the
      capsid translation initiation site in the 5' UTR were found to affect viral
      capsid mRNA polyadenylation, alternative translation, and progeny virus
      production. The results reveal that uATGs play an important role in the viral
      life cycle and represent a new layer to regulate HBoV1 RNA processing, which
      could be a target for gene therapy.

PMID- 30111561
TI  - Exploring Crimean-Congo Hemorrhagic Fever Virus-Induced Hepatic Injury Using
      Antibody-Mediated Type I Interferon Blockade in Mice.
AB  - Crimean-Congo hemorrhagic fever virus (CCHFV) can cause severe hepatic injury in
      humans. However, the mechanism(s) causing this damage is poorly characterized.
      CCHFV produces an acute disease, including liver damage, in mice lacking type I
      interferon (IFN-I) signaling due to either STAT-1 gene deletion or disruption of
      the IFN-I receptor 1 gene. Here, we explored CCHFV-induced liver pathogenesis in
      mice using an antibody to disrupt IFN-I signaling. When IFN-I blockade was
      induced within 24 h postexposure to CCHFV, mice developed severe disease with
      greater than 95% mortality by 6 days postexposure. In addition, we observed
      increased proinflammatory cytokines, chemoattractants, and liver enzymes in these
      mice. Extensive liver damage was evident by 4 days postexposure and was
      characterized by hepatocyte necrosis and the loss of CLEC4F-positive Kupffer
      cells. Similar experiments in CCHFV-exposed NOD-SCID-gamma (NSG), Rag2-deficient,
      and perforin-deficient mice also demonstrated liver injury, suggesting that
      cytotoxic immune cells are dispensable for hepatic damage. Some apoptotic liver
      cells contained viral RNA, while other apoptotic liver cells were negative,
      suggesting that cell death occurred by both intrinsic and extrinsic mechanisms.
      Protein and transcriptional analysis of livers revealed that activation of tumor
      necrosis factor superfamily members occurred by day 4 postexposure, implicating
      these molecules as factors in liver cell death. These data provide insights into
      CCHFV-induced hepatic injury and demonstrate the utility of antibody-mediated IFN
      I blockade in the study of CCHFV pathogenesis in mice.IMPORTANCE CCHFV is an
      important human pathogen that is both endemic and emerging throughout Asia,
      Africa, and Europe. A common feature of acute disease is liver injury ranging
      from mild to fulminant hepatic failure. The processes through which CCHFV induces
      severe liver injury are unclear, mostly due to the limitations of existing small
      animal systems. The only small-animal model in which CCHFV consistently produces
      severe liver damage is mice lacking IFN-I signaling. In this study, we used
      antibody-mediated blockade of IFN-I signaling in mice to study CCHFV liver
      pathogenesis in various transgenic mouse systems. We found that liver injury did
      not depend on cytotoxic immune cells and observed extensive activation of death
      receptor signaling pathways in the liver during acute disease. Furthermore, acute
      CCHFV infection resulted in a nearly complete loss of Kupffer cells. Our model
      system provides insight into both the molecular and the cellular features of
      CCHFV hepatic injury.

PMID- 30111562
TI  - Acute-Phase CD4+ T Cell Responses Targeting Invariant Viral Regions Are
      Associated with Control of Live Attenuated Simian Immunodeficiency Virus.
AB  - We manipulated SIVmac239Deltanef, a model of major histocompatibility complex
      (MHC)-independent viral control, to evaluate characteristics of effective
      cellular responses mounted by Mauritian cynomolgus macaques (MCMs) that express
      the M3 MHC haplotype, which has been associated with poor control of pathogenic
      simian immunodeficiency virus (SIV). We created SIVDeltanef-8x to test the
      hypothesis that effective SIV-specific T cell responses targeting invariant viral
      regions can emerge in the absence of immunodominant CD8+ T cell responses
      targeting variable epitopes and that control is achievable in individuals lacking
      known "protective" MHC alleles. Full-proteome gamma interferon (IFN-gamma) enzyme
      linked immunospot (ELISPOT) assays identified six newly targeted immunogenic
      regions following SIVDeltanef-8x infection of M3/M3 MCMs. We deep sequenced
      circulating virus and found that four of the six newly targeted regions rarely
      accumulated mutations. Six animals infected with SIVDeltanef-8x had T cell
      responses that targeted at least one of the four invariant regions and had a
      lower set point viral load than two animals that did not have T cell responses
      that targeted any invariant regions. We found that MHC class II molecules
      restricted all four of the invariant peptide regions, while the two variable
      regions were restricted by MHC class I molecules. Therefore, in the absence of
      immunodominant CD8+ T cell responses that target variable regions during
      SIVmac239Deltanef infection, individuals without protective MHC alleles developed
      predominantly CD4+ T cell responses specific for invariant regions that may
      improve control of virus replication. Our results provide some evidence that
      antiviral CD4+ T cells during acute SIV infection can contribute to effective
      viral control and should be considered in strategies to combat HIV
      infection.IMPORTANCE Studies defining effective cellular immune responses to
      human immunodeficiency virus (HIV) and SIV have largely focused on a rare
      population that express specific MHC class I alleles and control virus
      replication in the absence of antiretroviral treatment. This leaves in question
      whether similar effective immune responses can be achieved in the larger
      population. The majority of HIV-infected individuals mount CD8+ T cell responses
      that target variable viral regions that accumulate high-frequency escape
      mutations. Limiting T cell responses to these variable regions and targeting
      invariant viral regions, similar to observations in rare "elite controllers," may
      provide an ideal strategy for the development of effective T cell responses in
      individuals with diverse MHC genetics. Therefore, it is of paramount importance
      to determine whether T cell responses can be redirected toward invariant viral
      regions in individuals without protective MHC alleles and if these responses
      improve control of virus replication.

PMID- 30111564
TI  - The Human Cytomegalovirus Trimer and Pentamer Promote Sequential Steps in Entry
      into Epithelial and Endothelial Cells at Cell Surfaces and Endosomes.
AB  - Human cytomegalovirus (HCMV) infects a wide variety of human cell types by
      different entry pathways that involve distinct envelope glycoprotein complexes
      that include gH/gL, a trimer complex consisting of gHgL/gO, and a pentamer
      complex consisting of gH/gL/UL128/UL130/UL131. We characterized the effects of
      soluble forms of these proteins on HCMV entry. Soluble trimer and pentamer
      blocked entry of HCMV into epithelial and endothelial cells, whereas soluble
      gH/gL did not. Trimer inhibited HCMV entry into fibroblast cells, but pentamer
      and gH/gL did not. Both trimer and pentamer bound to the surfaces of fibroblasts
      and epithelial cells, whereas gH/gL did not bind to either cell type. Cell
      surface binding of trimer and pentamer did not involve heparin sulfate moieties.
      The ability of soluble trimer to block entry of HCMV into epithelial cells did
      not involve platelet-derived growth factor PDGFRalpha, which has been reported as
      a trimer receptor for fibroblasts. Soluble trimer reduced the amount of virus
      particles that could be adsorbed onto the surface of epithelial cells, whereas
      soluble pentamer had no effect on virus adsorption. However, soluble pentamer
      reduced the ability of virus particles to exit from early endosomes into the
      cytoplasm and then travel to the nucleus. These studies support a model in which
      both the trimer and pentamer are required for HCMV entry into epithelial and
      endothelial cells, with trimer interacting with cell surface receptors other than
      PDGFR and pentamer acting later in the entry pathway to promote egress from
      endosomes.IMPORTANCE HCMV infects nearly 80% of the world's population and causes
      significant morbidity and mortality. The current antiviral agents used to treat
      HCMV infections are prone to resistance and can be toxic to patients, and there
      is no current vaccine against HCMV available. The data in this report will lead
      to a better understanding of how essential HCMV envelope glycoproteins function
      during infection of biologically important cell types and will have significant
      implications for understanding HCMV pathogenesis for developing new therapeutics.

PMID- 30111563
TI  - NEURL3 is an inducible antiviral effector to inhibit HCV assembly by targeting
      viral E1 glycoprotein.
AB  - Hepatitis C virus (HCV) infection is a major cause of chronic hepatitis, liver
      cirrhosis and hepatocellular carcinoma. HCV can be sensed by host innate immunity
      to induce expression of interferons (IFNs) and a number of antiviral effectors.
      In this study, we found HCV infection induced the expression of Neuralized E3
      Ubiquitin Protein Ligase 3 (NEURL3), a putative E3 ligase, in a manner that
      requires the involvement of innate immune sensing but is independent of the IFN
      action. Furthermore, we showed that NEURL3 inhibited HCV infection, while had
      little effect on other RNA viruses including zika virus, dengue virus and
      vesicular stomatitis virus. Mechanistic studies demonstrated that NEURL3
      inhibited HCV assembly by directly binding HCV envelope glycoprotein E1 to
      interfere with the E1/E2 heterodimerization, an important prerequisite for virion
      morphogenesis. Finally, we showed that knockout of NEURL3 significantly enhanced
      HCV infection. In summary, we identified NEURL3 as a novel inducible antiviral
      host factor that suppresses HCV assembly. Our results not only shed new insight
      into how host innate immunity acts against HCV, but also revealed a new important
      biological function for NEURL3.IMPORTANCE The exact biological function of
      NEURL3, a putative E3 ligase remains largely unknown. In this study, we found
      that NEURL3 could be upregulated upon HCV infection in a manner dependent on
      pattern-recognition receptor-mediated innate immune response. NEURL3 inhibits HCV
      assembly by directly binding viral E1 envelope glycoprotein to disrupt its
      interaction with E2, an action that requires its NHR domain but not RING domain.
      Furthermore, we found that NEURL3 has a pan-genotypic anti-HCV activity and
      interacts with E1 of genotype 2a, 1b, 3a and 6a, but does not inhibit other
      closely related RNA viruses such as ZIKV, DENV and VSV. To our knowledge, our
      study is the first report to demonstrate that NEURL3 functions as an antiviral
      host factor. Our results not only shed new insight into how host innate immunity
      acts against HCV, but also revealed a new important biological function for
      NEURL3.

PMID- 30111565
TI  - In Vivo Persistence of Chimeric Virus after Substitution of the Kaposi's Sarcoma
      Associated Herpesvirus LANA DNA Binding Domain with That of Murid Herpesvirus 4.
AB  - The latency-associated nuclear antigen from Kaposi's sarcoma-associated
      herpesvirus (KSHV), kLANA, and its homolog from the murid herpesvirus 4 (MuHV-4),
      mLANA, are essential for viral latency. kLANA is nearly four times the size of
      mLANA, mainly due to an extensive central repeat region that is absent in mLANA.
      Both proteins harbor a C-terminal DNA binding domain (DBD). The DBD binds the
      terminal repeat (TR) DNA sequences of the viral genome to mediate persistence.
      Despite structural conservation, the kLANA and mLANA DBDs differ in sequence and
      mode of oligomerization. kLANA DBD oligomers are flexible and bent, while mLANA
      DBD oligomers bind DNA in a rigid, linear conformation. We previously reported
      that kLANA and mLANA acted reciprocally on TR sequences. Furthermore, a MuHV-4
      expressing kLANA instead of mLANA (v-kLANA) established latency in mice, albeit
      at a lower magnitude than the wild-type (WT) virus. Here, we asked if kLANA can
      accommodate the mLANA DBD and generated a fusion protein which contains kLANA but
      with the mLANA C-terminal region in place of that of kLANA. We report a
      recombinant MuHV-4 (v-KM) encoding this LANA fusion protein instead of mLANA. The
      fusion protein was expressed in lytic infection in vitro and assembled nuclear
      LANA dots in infected splenocytes. Results demonstrated that kLANA functionally
      accommodated mLANA's mode of DNA binding, allowing MuHV-4 chimeric virus to
      establish latency in vivo Notably, v-KM established latency in germinal center B
      cells more efficiently than did v-kLANA, although levels were reduced compared to
      WT MuHV-4.IMPORTANCE KSHV is a human oncogenic virus for which there is no
      tractable, immunocompetent animal model of infection. MuHV-4, a related rodent
      gammaherpesvirus, enables pathogenesis studies in mice. In latency, both viruses
      persist as extrachromosomal, circular genomes (episomes). LANA proteins encoded
      by KSHV (kLANA) and MuHV-4 (mLANA) contain a C-terminal DNA binding domain (DBD)
      that acts on the virus terminal repeats to enable episome persistence. mLANA is a
      smaller protein than kLANA. Their DBDs are structurally conserved but differ
      strikingly in the conformation of DNA binding. We report a recombinant, chimeric
      MuHV-4 which contains kLANA in place of mLANA, but in which the DBD is replaced
      with that of mLANA. Results showed that kLANA functionally accommodated mLANA's
      mode of DNA binding. In fact, the new chimeric virus established latency in vivo
      more efficiently than MuHV-4 expressing full-length kLANA.

PMID- 30111567
TI  - Using a virion assembly-defective dengue virus as a vaccine approach.
AB  - Dengue virus (DENV) is the most prevalent mosquito-transmitted viral pathogen in
      humans. The recently licensed dengue vaccine has major weaknesses. Therefore,
      there is an urgent need to develop improved dengue vaccines. Here we report a
      virion assembly-defective DENV as a novel vaccine platform. DENV containing an
      amino acid deletion (K188) in nonstructural protein 2A (NS2A) is fully competent
      in viral RNA replication, but is completely defective in virion assembly. When
      trans complemented with wild-type NS2A protein, the virion assembly defect could
      be rescued, generating pseudoinfectious virus (PIVNS2A) that can initiate single
      round infection. The trans-complementation efficiency could be significantly
      improved through selection for adaptive mutations, leading to high yield of
      PIVNS2A production with titers of >107 infectious forming units (IFU)/ml. Mice
      immunized with a single dose of PIVNS2A elicited strong T cell immune response
      and neutralization antibodies, and were protected from wild-type virus challenge.
      Collectively, the results have proved the concept of using assembly-defective
      virus as a new vaccine approach. The study has also solved the technical
      bottleneck to produce high yield of PIVNS2A vaccine. The technology could be
      applicable to vaccine development for other viral pathogens.IMPORTANCE Many
      flaviviruses are significant human pathogens that pose global threats to public
      health. Although licensed vaccines are available for yellow fever, Japanese
      encephalitis, tick-borne encephalitis, and dengue viruses, new approaches are
      needed to develop improved vaccines. Using dengue virus as a model, we report a
      novel vaccine platform by using a virion assembly-defective virus. We show that
      such assembly-defective virus could be rescued to higher titers, and infect cells
      for a single round. Mice immunized with the assembly-defective virus were
      protected from wild-type virus infection. This vaccine approach could be
      applicable to other viral pathogens.

PMID- 30111566
TI  - Semen exosomes promote transcriptional silencing of HIV-1 by disrupting NF
      kB/Sp1/Tat circuitry.
AB  - Exosomes play various roles in host responses to cancer and infective agents, and
      semen exosomes (SE) inhibit HIV-1 infection and transmission, although the
      mechanism(s) by which this occurs is unclear. Here, we show that SE block HIV-1
      proviral transcription at multiple transcriptional check points including
      transcription factor recruitment to the LTR, and transcription initiation and
      elongation. Biochemical and functional studies show that SE inhibit HIV-1 long
      terminal repeat (HIV-LTR)-driven viral gene expression and virus replication.
      Through partitioning of the HIV-1 RNA, we found that SE reduced the optimal
      expression of various viral RNA species. CHIP-RT-qPCR and EMSA analysis of
      infected cells identified human transcription factors NF-kB and Sp1, as well as
      RNA Pol II and the viral protein Tat as targets of SE. Of interest, SE inhibited
      HIV-1 LTR activation mediated by HIV-1 or Tat, but not by the mitogen PMA or
      TNFalpha. SE inhibited the DNA binding activities of NF-kB and Sp1 and blocked
      the recruitment of these transcription factors and Pol II to the HIV LTR
      promoter. Importantly, SE directly blocked NF-kB, Sp1, and Pol II binding to the
      LTR, and inhibited the interactions of Tat/NF-kB and Tat/Sp1, suggesting that SE
      mediated inhibition of the functional quadripartite complex-NF-kB-Sp1-Pol II-Tat,
      may be a novel mechanism of proviral transcription repression. These data provide
      a novel molecular basis for SE-mediated inhibition of HIV-1 and identify Tat as a
      potential target of SE.IMPORTANCE HIV is most commonly transmitted sexually, and
      semen is the primary vector. Despite progress in studies of HIV pathogenesis and
      the success of combination antiretroviral therapy in controlling viral
      replication, current therapy cannot completely control sexual transmission. Thus,
      there is need for identifying effective methods of controlling HIV replication
      and transmission. Recently, it was shown that human semen contains exosomes that
      protect against HIV infection in vitro. In this study, we identified a mechanism
      by which semen exosomes inhibited HIV-1 RNA expression. We found that semen
      exosomes inhibit recruitment of transcription factors NF-kB and Sp1, as well as
      RNA Pol II to the promoter region in the 5' long terminal repeat (LTR) of HIV-1.
      The HIV-1 early protein, transcriptional activator (Tat) was a target of semen
      exosomes, and semen exosomes inhibited the binding and recruitment of Tat to the
      HIV-1 LTR.

PMID- 30111568
TI  - The Endonucleolytic RNA Cleavage Function of nsp1 of Middle East Respiratory
      Syndrome Coronavirus Promotes the Production of Infectious Virus Particles in
      Specific Human Cell Lines.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) nsp1 suppresses host gene
      expression in expressed cells by inhibiting translation and inducing
      endonucleolytic cleavage of host mRNAs, the latter of which leads to mRNA decay.
      We examined the biological functions of nsp1 in infected cells and its role in
      virus replication by using wild-type MERS-CoV and two mutant viruses with
      specific mutations in the nsp1; one mutant lacked both biological functions,
      while the other lacked the RNA cleavage function but retained the translation
      inhibition function. In Vero cells, all three viruses replicated efficiently with
      similar replication kinetics, while wild-type virus induced stronger host
      translational suppression and host mRNA degradation than the mutants,
      demonstrating that nsp1 suppressed host gene expression in infected cells. The
      mutant viruses replicated less efficiently than wild-type virus in Huh-7 cells,
      HeLa-derived cells, and 293-derived cells, the latter two of which stably
      expressed a viral receptor protein. In 293-derived cells, the three viruses
      accumulated similar levels of nsp1 and major viral structural proteins and did
      not induce IFN-beta and IFN-lambda mRNAs; however, both mutants were unable to
      generate intracellular virus particles as efficiently as wild-type virus, leading
      to inefficient production of infectious viruses. These data strongly suggest that
      the endonucleolytic RNA cleavage function of the nsp1 promoted MERS-CoV assembly
      and/or budding in a 293-derived cell line. MERS-CoV nsp1 represents the first CoV
      gene 1 protein that plays an important role in virus assembly/budding and is the
      first identified viral protein whose RNA cleavage-inducing function promotes
      virus assembly/budding.IMPORTANCE MERS-CoV represents a high public health
      threat. Because CoV nsp1 is a major viral virulence factor, uncovering the
      biological functions of MERS-CoV nsp1 could contribute to our understanding of
      MERS-CoV pathogenicity and spur development of medical countermeasures. Expressed
      MERS-CoV nsp1 suppresses host gene expression, but its biological functions for
      virus replication and effects on host gene expression in infected cells are
      largely unexplored. We found that nsp1 suppressed host gene expression in
      infected cells. Our data further demonstrated that nsp1, which was not detected
      in virus particles, promoted virus assembly or budding in a 293-derived cell
      line, leading to efficient virus replication. These data suggest that nsp1 plays
      an important role in MERS-CoV replication and possibly affects virus-induced
      diseases by promoting virus particle production in infected hosts. Our data,
      which uncovered an unexpected novel biological function of nsp1 in virus
      replication, contribute to further understanding of the MERS-CoV replication
      strategies.

PMID- 30111569
TI  - Transcriptome Analysis of Infected and Bystander Type 2 Alveolar Epithelial Cells
      during Influenza A Virus Infection Reveals In Vivo Wnt Pathway Downregulation.
AB  - Influenza virus outbreaks remain a serious threat to public health. A greater
      understanding of how cells targeted by the virus respond to the infection can
      provide insight into the pathogenesis of disease. Here we examined the
      transcriptional profile of in vivo-infected and uninfected type 2 alveolar
      epithelial cells (AEC) in the lungs of influenza virus-infected mice. We show for
      the first time the unique gene expression profiles induced by the in vivo
      infection of AEC as well as the transcriptional response of uninfected bystander
      cells. This work allows us to distinguish the direct and indirect effects of
      infection at the cellular level. Transcriptome analysis revealed that although
      directly infected and bystander AEC from infected animals shared many
      transcriptome changes compared to AEC from uninfected animals, directly infected
      cells produce more interferon and express lower levels of Wnt signaling
      associated transcripts, while concurrently expressing more transcripts associated
      with cell death pathways, than bystander uninfected AEC. The Wnt signaling
      pathway was downregulated in both in vivo-infected AEC and in vitro-infected
      human lung epithelial A549 cells. Wnt signaling did not affect type I and III
      interferon production by infected A549 cells. Our results reveal unique
      transcriptional changes that occur within infected AEC and show that influenza
      virus downregulates Wnt signaling. In light of recent findings that Wnt signaling
      is essential for lung epithelial stem cells, our findings reveal a mechanism by
      which influenza virus may affect host lung repair.IMPORTANCE Influenza virus
      infection remains a major public health problem. Utilizing a recombinant green
      fluorescent protein-expressing influenza virus, we compared the in vivo
      transcriptomes of directly infected and uninfected bystander cells from infected
      mouse lungs and discovered many pathways uniquely regulated in each population.
      The Wnt signaling pathway was downregulated in directly infected cells and was
      shown to affect virus but not interferon production. Our study is the first to
      discern the in vivo transcriptome changes induced by direct viral infection
      compared to mere exposure to the lung inflammatory milieu and highlight the
      downregulation of Wnt signaling. This downregulation has important implications
      for understanding influenza virus pathogenesis, as Wnt signaling is critical for
      lung epithelial stem cells and lung epithelial cell differentiation. Our findings
      reveal a mechanism by which influenza virus may affect host lung repair and
      suggest interventions that prevent damage or accelerate recovery of the lung.

PMID- 30111573
TI  - Reversals in life expectancy in high income countries?

PMID- 30111570
TI  - Sequence Variation of Epstein-Barr Virus: Viral Types, Geography, Codon Usage,
      and Diseases.
AB  - One hundred thirty-eight new Epstein-Barr virus (EBV) genome sequences have been
      determined. One hundred twenty-five of these and 116 from previous reports were
      combined to produce a multiple-sequence alignment of 241 EBV genomes, which we
      have used to analyze variation within the viral genome. The type 1/type 2
      classification of EBV remains the major form of variation and is defined mostly
      by EBNA2 and EBNA3, but the type 2 single-nucleotide polymorphisms (SNPs) at the
      EBNA3 locus extend into the adjacent gp350 and gp42 genes, whose products mediate
      infection of B cells by EBV. A small insertion within the BART microRNA region of
      the genome was present in 21 EBV strains. EBV from saliva of U.S. patients with
      chronic active EBV infection aligned with the wild-type EBV genome with no
      evidence of WZhet rearrangements. The V3 polymorphism in the Zp promoter for
      BZLF1 was found to be frequent in nasopharyngeal carcinoma cases from both Hong
      Kong and Indonesia. Codon usage was found to differ between latent and lytic
      cycle EBV genes, and the main forms of variation of the EBNA1 protein have been
      identified.IMPORTANCE Epstein-Barr virus causes most cases of infectious
      mononucleosis and posttransplant lymphoproliferative disease. It contributes to
      several types of cancer, including Hodgkin's lymphoma, Burkitt's lymphoma,
      diffuse large B cell lymphoma, nasopharyngeal carcinoma, and gastric carcinoma.
      EBV genome variation is important because some of the diseases associated with
      EBV have very different incidences in different populations and geographic
      regions, and differences in the EBV genome might contribute to these diseases.
      Some specific EBV genome alterations that appear to be significant in EBV
      associated cancers are already known, and current efforts to make an EBV vaccine
      and antiviral drugs should also take account of sequence differences in the
      proteins used as targets.

PMID- 30111574
TI  - Mitochondrial-derived reactive oxygen species influence ADP sensitivity, but not
      CPT-I substrate sensitivity.
AB  - The mechanisms regulating oxidative phosphorylation during exercise remain poorly
      defined; however, key mitochondrial proteins, including carnitine
      palmitoyltransferase-I (CPT-I) and adenine nucleotide translocase, have redox
      sensitive sites. Interestingly, muscle contraction has recently been shown to
      increase mitochondrial membrane potential and reactive oxygen species (ROS)
      production; therefore, we aimed to determine if mitochondrial-derived ROS
      influences bioenergetic responses to exercise. Specifically, we examined the
      influence of acute exercise on mitochondrial bioenergetics in WT (wild type) and
      transgenic mice (MCAT, mitochondrial-targeted catalase transgenic) possessing
      attenuated mitochondrial ROS. We found that ablating mitochondrial ROS did not
      alter palmitoyl-CoA (P-CoA) respiratory kinetics or influence the exercise
      mediated reductions in malonyl CoA sensitivity, suggesting that mitochondrial ROS
      does not regulate CPT-I. In contrast, while mitochondrial protein content,
      maximal coupled respiration, and ADP (adenosine diphosphate) sensitivity in
      resting muscle were unchanged in the absence of mitochondrial ROS, exercise
      increased the apparent ADP K m (decreased ADP sensitivity) ~30% only in WT mice.
      Moreover, while the presence of P-CoA decreased ADP sensitivity, it did not
      influence the basic response to exercise, as the apparent ADP K m was increased
      only in the presence of mitochondrial ROS. This basic pattern was also mirrored
      in the ability of ADP to suppress mitochondrial H2O2 emission rates, as exercise
      decreased the suppression of H2O2 only in WT mice. Altogether, these data
      demonstrate that while exercise-induced mitochondrial-derived ROS does not
      influence CPT-I substrate sensitivity, it inhibits ADP sensitivity independent of
      P-CoA. These data implicate mitochondrial redox signaling as a regulator of
      oxidative phosphorylation.

PMID- 30111572
TI  - Sirtuin 2 Isoform 1 Enhances Hepatitis B Virus RNA Transcription and DNA
      Synthesis via the AKT/GSK-3beta/beta-Catenin Signaling Pathway.
AB  - Sirtuin 2 (Sirt2), a NAD+-dependent protein deacetylase, is overexpressed in many
      hepatocellular carcinomas (HCCs) and can deacetylate many proteins, including
      tubulins and AKT prior to AKT activation. Here, we found that endogenous Sirt2
      was upregulated in hepatitis B virus (HBV) WT-replicating cells, leading to
      tubulin deacetylation; however, this was not the case in HBV replication
      deficient mutant-transfected cells and 1.3mer HBV WT-transfected plus reverse
      transcriptase inhibitor (entecavir or lamivudine) treated cells but all HBV
      proteins are expressed. In HBV WT-replicating cells, upregulation of Sirt2
      induced AKT activation, which consequently downregulated glycogen synthase kinase
      (GSK-3beta) and increased beta-catenin levels; however, downregulation of Sirt2
      in HBV non-replicating cells impaired AKT/GSK-3beta/beta-catenin signaling.
      Overexpression of Sirt2 isoform 1 stimulated HBV transcription and consequently
      HBV DNA synthesis, which in turn activates AKT and consequently increases beta
      catenin levels, possibly through physical interactions with Sirt2 and AKT.
      Knockdown of Sirt2 by shRNAs or inhibition by AGK2 or dominant-negative mutant
      expression inhibited HBV replication, reduced AKT activation, and decreased beta
      catenin levels. Through HBV infection, we demonstrated that Sirt2 knockdown
      inhibited HBV replication from transcription. Although HBx itself activates AKT
      and upregulates beta-catenin, Sirt2-mediated signaling and upregulated HBV
      replication were HBx-independent. Since constitutively active AKT inhibits HBV
      replication, the results suggest that upregulated Sirt2 and activated AKT may
      balance HBV replication to prolong viral replication, eventually leading to
      development of HCC. Also, the results indicate that Sirt2 inhibition may be a new
      therapeutic option for controlling HBV infection and preventing HCC.IMPORTANCE OF
      THIS STUDYEven though Sirt2, a NAD+-dependent protein deacetylase, is
      overexpressed in many HCCs, and overexpressed Sirt2 promotes hepatic fibrosis and
      associates positively with vascular invasion by primary HCCs via AKT/GSK
      3beta/beta-catenin signaling, the relationships between Sirt2, HBV, HBx, and/or
      HBV-associated hepatocarcinogenesis are unclear. Here, we show that HBV DNA
      replication, not HBV expression, correlates positively with Sirt2 upregulation
      and AKT activation. We demonstrate that overexpression of Sirt2 further increases
      HBV replication and increases AKT activation, downregulates GSK-3beta, and
      increases beta-catenin levels. Conversely, inhibiting Sirt2 decreases HBV
      replication, reduces AKT activation, and decreases beta-catenin. Although HBx
      activates AKT to upregulate beta-catenin, Sirt2-mediated effects were not
      dependent on HBx. The results also indicate that a Sirt2 inhibitor may control
      HBV infection and prevent development of hepatic fibrosis and HCC.

PMID- 30111575
TI  - The D' domain of von Willebrand factor requires the presence of the D3 domain for
      optimal factor VIII binding.
AB  - The D'-D3 fragment of von Willebrand factor (VWF) can be divided into TIL'-E'
      VWD3-C8_3-TIL3-E3 subdomains of which TIL'-E'-VWD3 comprises the main factor VIII
      (FVIII)-binding region. Yet, von Willebrand disease (VWD) Type 2 Normandy (2N)
      mutations, associated with impaired FVIII interaction, have been identified in
      C8_3-TIL3-E3. We now assessed the role of the VWF (sub)domains for FVIII binding
      using isolated D', D3 and monomeric C-terminal subdomain truncation variants of
      D'-D3. Competitive binding assays and surface plasmon resonance analysis revealed
      that D' requires the presence of D3 for effective interaction with FVIII. The
      isolated D3 domain, however, did not show any FVIII binding. Results indicated
      that the E3 subdomain is dispensable for FVIII binding. Subsequent deletion of
      the other subdomains from D3 resulted in a progressive decrease in FVIII-binding
      affinity. Chemical footprinting mass spectrometry suggested increased
      conformational changes at the N-terminal side of D3 upon subsequent subdomain
      deletions at the C-terminal side of the D3. A D'-D3 variant with a VWD type 2N
      mutation in VWD3 (D879N) or C8_3 (C1060R) also revealed conformational changes in
      D3, which were proportional to a decrease in FVIII-binding affinity. A D'-D3
      variant with a putative VWD type 2N mutation in the E3 subdomain (C1225G) showed,
      however, normal binding. This implies that the designation VWD type 2N is
      incorrect for this variant. Results together imply that a structurally intact D3
      in D'-D3 is indispensable for effective interaction between D' and FVIII
      explaining why specific mutations in D3 can impair FVIII binding.

PMID- 30111571
TI  - Infection Dynamics of Hepatitis E Virus in Wild-Type and Immunoglobulin Heavy
      Chain Knockout JH -/- Gnotobiotic Piglets.
AB  - Hepatitis E virus (HEV), the causative agent of hepatitis E, is an important but
      incompletely understood pathogen causing high mortality during pregnancy and
      leading to chronic hepatitis in immunocompromised individuals. The underlying
      mechanisms leading to hepatic damage remain unknown; however, the humoral immune
      response is implicated. In this study, immunoglobulin (Ig) heavy chain JH -/-
      knockout gnotobiotic pigs were generated using CRISPR/Cas9 technology to deplete
      the B-lymphocyte population, resulting in an inability to generate a humoral
      immune response to genotype 3 HEV infection. Compared to wild-type gnotobiotic
      piglets, the frequencies of B lymphocytes in the Ig heavy chain JH -/- knockouts
      were significantly lower, despite similar levels of other innate and adaptive T
      lymphocyte cell populations. The dynamic of acute HEV infection was subsequently
      determined in heavy chain JH -/- knockout and wild-type gnotobiotic pigs. The
      data showed that wild-type piglets had higher viral RNA loads in feces and sera
      compared to the JH -/- knockout pigs, suggesting that the Ig heavy chain JH -/-
      knockout in pigs actually decreased the level of HEV replication. Both HEV
      infected wild-type and JH -/- knockout gnotobiotic piglets developed more
      pronounced lymphoplasmacytic hepatitis and hepatocellular necrosis lesions than
      other studies with conventional pigs. The HEV-infected JH -/- knockout pigs also
      had significantly enlarged livers both grossly and as a ratio of liver/body
      weight compared to phosphate-buffered saline-inoculated groups. This novel
      gnotobiotic pig model will aid in future studies into HEV pathogenicity, an
      aspect which has thus far been difficult to reproduce in the available animal
      model systems.IMPORTANCE According to the World Health Organization,
      approximately 20 million HEV infections occur annually, resulting in 3.3 million
      cases of hepatitis E and >44,000 deaths. The lack of an efficient animal model
      that can mimic the full-spectrum of infection outcomes hinders our ability to
      delineate the mechanism of HEV pathogenesis. Here, we successfully generated
      immunoglobulin heavy chain JH -/- knockout gnotobiotic pigs using CRISPR/Cas9
      technology, established a novel JH -/- knockout and wild-type gnotobiotic pig
      model for HEV, and systematically determined the dynamic of acute HEV infection
      in gnotobiotic pigs. It was demonstrated that knockout of the Ig heavy chain in
      pigs decreased the level of HEV replication. Infected wild-type and JH -/-
      knockout gnotobiotic piglets developed more pronounced HEV-specific lesions than
      other studies using conventional pigs, and the infected JH -/- knockout pigs had
      significantly enlarged livers. The availability of this novel model will
      facilitate future studies of HEV pathogenicity.

PMID- 30111576
TI  - Complement C3 Inhibition Modulates Neurodegeneration in Chronic Traumatic Brain
      Injury.

PMID- 30111578
TI  - MT1-MMP targeting to endolysosomes is mediated by upregulation of flotillins.
AB  - Tumor cell invasion and metastasis formation are the major cause of death in
      cancer patients. These processes rely on extracellular matrix (ECM) degradation
      mediated by organelles termed invadopodia, to which the transmembrane matrix
      metalloproteinase MT1-MMP (also known as MMP14) is delivered from its reservoir,
      the RAB7-containing endolysosomes. How MT1-MMP is targeted to endolysosomes
      remains to be elucidated. Flotillin-1 and -2 are upregulated in many invasive
      cancers. Here, we show that flotillin upregulation triggers a general mechanism,
      common to carcinoma and sarcoma, which promotes RAB5-dependent MT1-MMP
      endocytosis and its delivery to RAB7-positive endolysosomal reservoirs.
      Conversely, flotillin knockdown in invasive cancer cells greatly reduces MT1-MMP
      accumulation in endolysosomes, its subsequent exocytosis at invadopodia, ECM
      degradation and cell invasion. Our results demonstrate that flotillin
      upregulation is necessary and sufficient to promote epithelial and mesenchymal
      cancer cell invasion and ECM degradation by controlling MT1-MMP endocytosis and
      delivery to the endolysosomal recycling compartment.

PMID- 30111580
TI  - TBC1D5 controls the GTPase cycle of Rab7b.
AB  - Rab GTPases are key regulators of intracellular trafficking, and cycle between a
      GTP-bound active state and a GDP-bound inactive state. This cycle is regulated by
      guanine-nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs).
      Several efforts have been made in connecting the correct GEFs and GAPs to their
      specific Rab. Here, we aimed to identify GAPs for Rab7b, the small GTPase
      involved in transport from late endosomes to the trans-Golgi. An siRNA screen
      targeting proteins containing TBC domains critical for Rab GAPs was performed and
      coupled to a phenotypic read-out that visualized the distribution of Rab7b.
      Silencing of TBC1D5 provided the strongest phenotype and this protein was
      subsequently validated in various in vitro and cell-based assays. TBC1D5
      localizes to Rab7b-positive vesicles, interacts with Rab7b and has GAP activity
      towards Rab7b in vitro, which is further increased by retromer proteins.
      Similarly to the constitutively active mutant of Rab7b, inactivation of TBC1D5
      also reduces the number of CI-MPR- and sortilin-positive vesicles. Together, the
      results show that TBC1D5 is a GAP for Rab7b in the control of endosomal transport
      to the trans-Golgi.This article has an associated First Person interview with the
      first author of the paper.

PMID- 30111579
TI  - Rab6 promotes insulin receptor and cathepsin trafficking to regulate autophagy
      induction and activity in Drosophila.
AB  - The self-degradative process of autophagy is important for energy homeostasis and
      cytoplasmic renewal. This lysosome-mediated pathway is negatively regulated by
      the target of rapamycin kinase (TOR) under basal conditions, and requires the
      vesicle trafficking machinery regulated by Rab GTPases. However, the interactions
      between autophagy, TOR and Rab proteins remain incompletely understood in vivo
      Here, we identify Rab6 as a critical regulator of the balance between TOR
      signaling and autolysosome function. Loss of Rab6 causes an accumulation of
      enlarged autophagic vesicles resulting in part from a failure to deliver
      lysosomal hydrolases, rendering autolysosomes with a reduced degradative capacity
      and impaired turnover. Additionally, Rab6-deficient cells are reduced in size and
      display defective insulin-TOR signaling as a result of mis-sorting and
      internalization of the insulin receptor. Our findings suggest that Rab6 acts to
      maintain the reciprocal regulation between autophagy and TOR activity during
      distinct nutrient states, thereby balancing autophagosome production and turnover
      to avoid autophagic stress.

PMID- 30111581
TI  - Nuclear exclusion of SMAD2/3 in granulosa cells is associated with primordial
      follicle activation in the mouse ovary.
AB  - Maintenance and activation of the limited supply of primordial follicles in the
      ovary are important determinants of reproductive lifespan. Currently, the
      molecular programme that maintains the primordial phenotype and the early events
      associated with follicle activation are not well defined. Here, we have
      systematically analysed these events using microscopy and detailed image
      analysis. Using the immature mouse ovary as a model, we demonstrate that the
      onset of granulosa cell (GC) proliferation results in increased packing density
      on the oocyte surface and consequent GC cuboidalization. These events precede
      oocyte growth and nuclear translocation of FOXO3a, a transcription factor
      important in follicle activation. Immunolabelling of the TGFbeta signalling
      mediators and transcription factors SMAD2/3 revealed a striking expression
      pattern specific to GCs of small follicles. SMAD2/3 were expressed in the nuclei
      of primordial GCs but were mostly excluded in early growing follicles. In
      activated follicles, GC nuclei lacking SMAD2/3 generally expressed Ki67. These
      findings suggest that the first phenotypic changes during follicle activation are
      observed in GCs, and that TGFbeta signalling is fundamental for regulating GC
      arrest and the onset of proliferation.

PMID- 30111582
TI  - The N-recognin UBR4 of the N-end rule pathway is targeted to and required for the
      biogenesis of the early endosome.
AB  - The N-end rule pathway is a proteolytic system in which single N-terminal
      residues of proteins act as N-degrons. These degrons are recognized by N
      recognins, facilitating substrate degradation via the ubiquitin (Ub) proteasome
      system (UPS) or autophagy. We have previously identified a set of N-recognins
      [UBR1, UBR2, UBR4 (also known as p600) and UBR5 (also known as EDD)] that bind N
      degrons through their UBR boxes to promote proteolysis by the proteasome. Here,
      we show that the 570 kDa N-recognin UBR4 is associated with maturing endosomes
      through an interaction with Ca2+-bound calmodulin. The endosomal recruitment of
      UBR4 is essential for the biogenesis of early endosomes (EEs) and endosome
      related processes, such as the trafficking of endocytosed protein cargos and
      degradation of extracellular cargos by endosomal hydrolases. In mouse embryos,
      UBR4 marks and plays a role in the endosome-lysosome pathway that mediates the
      heterophagic proteolysis of endocytosed maternal proteins into amino acids. By
      screening 9591 drugs through the DrugBank database, we identify picolinic acid as
      a putative ligand for UBR4 that inhibits the biogenesis of EEs. Our results
      suggest that UBR4 is an essential modulator in the endosome-lysosome system.This
      article has an associated First Person interview with the first author of the
      paper.

PMID- 30111577
TI  - Perinatal Streptococcus agalactiae Epidemiology and Surveillance Targets.
AB  - SUMMARYStreptococcus agalactiae, or group B streptococcus (GBS), is a major
      neonatal pathogen. Recent data have elucidated the global prevalence of maternal
      and neonatal colonization, but gaps still remain in the epidemiology of this
      species. A number of phenotypic and genotypic classifications can be used to
      identify the diversity of GBS strains, and some are more discriminatory than
      others. This review explores the main schemes used for GBS epidemiology and
      further details the targets for epidemiological surveillance. Current screening
      practices across the world provide a unique opportunity to gain detailed
      information on maternal colonizing strains and neonatal disease-causing strains,
      which is vital for monitoring and therapeutics, if sufficient detail can be
      extracted. Deciphering which isolates are circulating within specific populations
      and recording targets within invasive strains are crucial steps in monitoring the
      implementation of therapeutics, such as vaccines, as well as developing novel
      therapies against prevalent GBS strains. Having a detailed understanding of
      global GBS epidemiology will prove invaluable for understanding the pathogenesis
      of this organism and equipping future prevention strategies for success.

PMID- 30111583
TI  - Identification of Miro1 and Miro2 as mitochondrial receptors for myosin XIX.
AB  - Mitochondrial distribution in cells is critical for cellular function and proper
      inheritance during cell division. In mammalian cells, mitochondria are
      transported predominantly along microtubules by kinesin and dynein motors that
      bind indirectly via TRAK1 and TRAK2 to outer mitochondrial membrane proteins
      Miro1 and Miro2 (Miro1/2). Here, using proximity labelling, we identified Miro1/2
      as potential binding partners of myosin XIX (Myo19). Interaction studies show
      that Miro1 binds directly to a C-terminal fragment of the Myo19 tail region and
      that Miro1/2 recruit the Myo19 tail in vivo This recruitment is regulated by the
      nucleotide state of the N-terminal Rho-like GTPase domain of Miro1/2. Notably,
      Myo19 protein stability in cells depends on its association with Miro1/2.
      Downregulation of Miro1/2 or overexpression of the adaptor proteins TRAK1 and
      TRAK2 caused a reduction in Myo19 protein levels. Myo19 regulates the subcellular
      distribution of mitochondria, and downregulation, as well as overexpression, of
      Myo19 induced perinuclear collapse of mitochondria, phenocopying loss of the
      kinesin KIF5, dynein or their mitochondrial receptors Miro1/2. These results
      suggest that Miro1 and Miro2 coordinate microtubule- and actin-based
      mitochondrial movement.This article has an associated First Person interview with
      the first author of the paper.

PMID- 30111585
TI  - Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease: A Focus on
      Heart Failure.

PMID- 30111584
TI  - Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease: Atrial
      Fibrillation.

PMID- 30111586
TI  - Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease: Sudden
      Cardiac Death.

PMID- 30111587
TI  - The ABCs in the Mapping Progress in Reducing Cardiovascular Risk with Kidney
      Disease: An Introductory Remark on Expert Perspectives.

PMID- 30111588
TI  - Mapping Progress in Reducing Cardiovascular Risk with Kidney Disease: Managing
      Volume Overload.

PMID- 30111591
TI  - Nur77 variants solely comprising the amino-terminal domain activate hypoxia
      inducible factor-1alpha and affect bone marrow homeostasis in mice and humans.
AB  - Gene targeting via homologous recombination can occasionally result in incomplete
      disruption of the targeted gene. Here, we show that a widely used Nur77-deficient
      transgenic mouse model expresses a truncated protein encoding for part of the N
      terminal domain of nuclear receptor Nur77. This truncated Nur77 protein is absent
      in a newly developed Nur77-deficient mouse strain generated using Cre-Lox
      recombination. Comparison of these two mouse strains using immunohistochemistry,
      flow cytometry, and colony-forming assays shows that homologous recombination
      derived Nur77-deficient mice, but not WT or Cre-Lox-derived Nur77-deficient mice,
      suffer from liver immune cell infiltrates, loss of splenic architecture, and
      increased numbers of bone marrow hematopoietic stem cells and splenic colony
      forming cells with age. Mechanistically, we demonstrate that the truncated Nur77
      N-terminal domain protein maintains the stability and activity of hypoxia
      inducible factor (HIF)-1, a transcription factor known to regulate bone marrow
      homeostasis. Additionally, a previously discovered, but uncharacterized, human
      Nur77 transcript variant that encodes solely for its N-terminal domain,
      designated TR3beta, can also stabilize and activate HIF-1alpha. Meta-analysis of
      publicly available microarray data sets shows that TR3beta is highly expressed in
      human bone marrow cells and acute myeloid leukemia samples. In conclusion, our
      study provides evidence that a transgenic mouse model commonly used to study the
      biological function of Nur77 has several major drawbacks, while simultaneously
      identifying the importance of nongenomic Nur77 activity in the regulation of bone
      marrow homeostasis.

PMID- 30111589
TI  - Mouse models in the era of large human tumour sequencing studies.
AB  - Cancer is a complex disease in which cells progressively accumulate mutations
      disrupting their cellular processes. A fraction of these mutations drive
      tumourigenesis by affecting oncogenes or tumour suppressor genes, but many
      mutations are passengers with no clear contribution to tumour development. The
      advancement of DNA and RNA sequencing technologies has enabled in-depth analysis
      of thousands of human tumours from various tissues to perform systematic
      characterization of their (epi)genomes and transcriptomes in order to identify
      (epi)genetic changes associated with cancer. Combined with considerable progress
      in algorithmic development, this expansion in scale has resulted in the
      identification of many cancer-associated mutations, genes and pathways that are
      considered to be potential drivers of tumour development. However, it remains
      challenging to systematically identify drivers affected by complex genomic
      rearrangements and drivers residing in non-coding regions of the genome or in
      complex amplicons or deletions of copy-number driven tumours. Furthermore,
      functional characterization is challenging in the human context due to the lack
      of genetically tractable experimental model systems in which the effects of
      mutations can be studied in the context of their tumour microenvironment. In this
      respect, mouse models of human cancer provide unique opportunities for
      pinpointing novel driver genes and their detailed characterization. In this
      review, we provide an overview of approaches for complementing human studies with
      data from mouse models. We also discuss state-of-the-art technological
      developments for cancer gene discovery and validation in mice.

PMID- 30111590
TI  - Leader of the SAC: molecular mechanisms of Mps1/TTK regulation in mitosis.
AB  - Discovered in 1991 in a screen for genes involved in spindle pole body
      duplication, the monopolar spindle 1 (Mps1) kinase has since claimed a central
      role in processes that ensure error-free chromosome segregation. As a result,
      Mps1 kinase activity has become an attractive candidate for pharmaceutical
      companies in the search for compounds that target essential cellular processes to
      eliminate, for example, tumour cells or pathogens. Research in recent decades has
      offered many insights into the molecular function of Mps1 and its regulation. In
      this review, we integrate the latest knowledge regarding the regulation of Mps1
      activity and its spatio-temporal distribution, highlight gaps in our
      understanding of these processes and propose future research avenues to address
      them.

PMID- 30111593
TI  - Poxviral protein E3-altered cytokine production reveals that DExD/H-box helicase
      9 controls Toll-like receptor-stimulated immune responses.
AB  - Host pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs)
      detect viruses and other pathogens, inducing production of cytokines that cause
      inflammation and mobilize cells to control infection. Vaccinia virus (VACV)
      encodes proteins that antagonize these host innate immune responses, and
      elucidating the mechanisms of action of these viral proteins helped shed light on
      PRR signaling mechanisms. The VACV virulence factor E3 is one of the most
      intensely studied VACV proteins and has multiple effects on host cells, many of
      which cannot be explained by the currently known cellular targets of E3. Here, we
      report that E3 expression in human monocytes alters TLR2- and TLR8-dependent
      cytokine induction, and particularly inhibits interleukin (IL)-6. Using MS, we
      identified DExD/H-box helicase 9 (DHX9) as an E3 target. Although DHX9 has
      previously been implicated as a PRR for sensing nucleic acid in dendritic cells,
      we found no role for DHX9 as a nucleic acid-sensing PRR in monocytes. Rather,
      DHX9 suppression in these cells phenocopied the effects of E3 expression on TLR2-
      and TLR8-dependent cytokine induction, in that DHX9 was required for all TLR8
      dependent cytokines measured, and for TLR2-dependent IL-6. Furthermore, DHX9 also
      had a cell- and stimulus-independent role in IL-6 promoter induction. DHX9
      enhanced NF-kappaB-dependent IL-6 promoter activation, which was directly
      antagonized by E3. These results indicate new roles for DHX9 in regulating
      cytokines in innate immunity and reveal that VACV E3 disrupts innate immune
      responses by targeting of DHX9.

PMID- 30111592
TI  - The nucleoside-diphosphate kinase NME3 associates with nephronophthisis proteins
      and is required for ciliary function during renal development.
AB  - Nephronophthisis (NPH) is an autosomal recessive renal disease leading to kidney
      failure in children and young adults. The protein products of the corresponding
      genes (NPHPs) are localized in primary cilia or their appendages. Only about 70%
      of affected individuals have a mutation in one of 100 renal ciliopathy genes, and
      no unifying pathogenic mechanism has been identified. Recently, some NPHPs,
      including NIMA-related kinase 8 (NEK8) and centrosomal protein 164 (CEP164), have
      been found to act in the DNA-damage response pathway and to contribute to genome
      stability. Here, we show that NME/NM23 nucleoside-diphosphate kinase 3 (NME3)
      that has recently been found to facilitate DNA-repair mechanisms binds to several
      NPHPs, including NEK8, CEP164, and ankyrin repeat and sterile alpha motif domain
      containing 6 (ANKS6). Depletion of nme3 in zebrafish and Xenopus resulted in
      typical ciliopathy-associated phenotypes, such as renal malformations and left
      right asymmetry defects. We further found that endogenous NME3 localizes to the
      basal body and that it associates also with centrosomal proteins, such as NEK6,
      which regulates cell cycle arrest after DNA damage. The ciliopathy-typical
      manifestations of NME3 depletion in two vertebrate in vivo models, the
      biochemical association of NME3 with validated NPHPs, and its localization to the
      basal body reveal a role for NME3 in ciliary function. We conclude that mutations
      in the NME3 gene may aggravate the ciliopathy phenotypes observed in humans.

PMID- 30111594
TI  - Mosquito-borne transmission in urban landscapes: the missing link between vector
      abundance and human density.
AB  - With escalating urbanization, the environmental, demographic, and socio-economic
      heterogeneity of urban landscapes poses a challenge to mathematical models for
      the transmission of vector-borne infections. Classical coupled vector-human
      models typically assume that mosquito abundance is either independent from, or
      proportional to, human population density, implying a decreasing force of
      infection, or per capita infection rate with host number. We question these
      assumptions by introducing an explicit dependence between host and vector
      densities through different recruitment functions, whose dynamical consequences
      we examine in a modified model formulation. Contrasting patterns in the force of
      infection are demonstrated, including in particular increasing trends when
      recruitment grows sufficiently fast with human density. Interaction of these
      patterns with seasonality in temperature can give rise to pronounced differences
      in timing, relative peak sizes, and duration of epidemics. These proposed
      dependencies explain empirical dengue risk patterns observed in the city of Delhi
      where socio-economic status has an impact on both human and mosquito densities.
      These observed risk trends with host density are inconsistent with current
      standard models. A better understanding of the connection between vector
      recruitment and host density is needed to address the population dynamics of
      mosquito-transmitted infections in urban landscapes.

PMID- 30111595
TI  - Genetic determination of migration strategies in large soaring birds: evidence
      from hybrid eagles.
AB  - The relative contributions of genetic and social factors in shaping the living
      world are a crucial question in ecology. The annual migration of birds to their
      wintering grounds and back provides significant knowledge in this field of
      research. Migratory movements are predominantly genetically determined in
      passerine birds, while in large soaring birds, it is presumed that social
      (cultural) factors play the largest role. In this study, we show that genetic
      factors in soaring birds are more important than previously assumed. We used
      global positioning system (GPS)-telemetry to compare the autumn journeys and
      wintering ranges of two closely related large raptorial bird species, the greater
      spotted eagle Clanga clanga and the lesser spotted eagle Clanga pomarina, and
      hybrids between them. The timing of migration in hybrids was similar to that of
      one parental species, but the wintering distributions and home range sizes were
      similar to those of the other. Tracking data were supported by habitat
      suitability modelling, based on GPS fixes and ring recoveries. These results
      suggest a strong genetic influence on migration strategy via a trait-dependent
      dominance effect, although we cannot rule out the contribution of social
      interactions.

PMID- 30111596
TI  - Information use during movement regulates how fragmentation and loss of habitat
      affect body size.
AB  - An individual's body size is central to its behaviour and physiology, and tightly
      linked to its movement ability. The spatial arrangement of resources and a
      consumer's capacity to locate them are therefore expected to exert strong
      selection on consumer body size. We investigated the evolutionary impact of both
      the fragmentation and loss of habitat on consumer body size and its feedback
      effects on resource distribution, under varying levels of information used during
      habitat choice. We developed a mechanistic, individual-based, spatially explicit
      model, including several allometric rules for key consumer traits. Our model
      reveals that as resources become more fragmented and scarce, informed habitat
      choice selects for larger body sizes while random habitat choice promotes small
      sizes. Information use may thus be an overlooked explanation for the observed
      variation in body size responses to habitat fragmentation. Moreover, we find that
      resources can accumulate and aggregate if information about resource abundance is
      incomplete. Informed movement results in stable resource-consumer dynamics and
      controlled resources across space. However, habitat loss and fragmentation
      destabilize local dynamics and disturb resource suppression by the consumer.
      Considering information use during movement is thus critical to understand the
      eco-evolutionary dynamics underlying the functioning and structuring of consumer
      communities.

PMID- 30111597
TI  - Why war is a man's game.
AB  - Interest in the evolutionary origins and drivers of warfare in ancient and
      contemporary small-scale human societies has greatly increased in the last
      decade, and has been particularly spurred by exciting archaeological discoveries
      that suggest our ancestors led more violent lives than previously documented.
      However, the striking observation that warfare is an almost-exclusively male
      activity remains unexplained. Three general hypotheses have been proposed,
      concerning greater male effectiveness in warfare, lower male costs, and
      patrilocality. But while each of these factors might explain why warfare is more
      common in men, they do not convincingly explain why women almost never
      participate. Here, we develop a mathematical model to formally assess these
      hypotheses. Surprisingly, we find that exclusively male warfare may evolve even
      in the absence of any such sex differences, though sex biases in these parameters
      can make this evolutionary outcome more likely. The qualitative observation that
      participation in warfare is almost exclusive to one sex is ultimately explained
      by the fundamentally sex-specific nature of Darwinian competition-in fitness
      terms, men compete with men and women with women. These results reveal a
      potentially key role for ancestral conditions in shaping our species' patterns of
      sexual division of labour and violence-related adaptations and behavioural
      disorders.

PMID- 30111598
TI  - Female perception of copulatory courtship by male titillators in a bushcricket.
AB  - Males of the bushcricket Metrioptera roeselii bear paired titillators that are
      spiny genital structures supposedly functioning as copulatory courtship devices.
      During copulation, the male inserts its titillators into the female's genital
      chamber, where they rhythmically tap on the sensilla-covered dorsal surface of
      the genital fold. Here, we investigated the stimulatory function of male
      titillators during mating in M. roeselii Tracer backfills of presumptive
      mechanosensory sensilla at the female genital fold revealed a thick bundle of
      sensory axons entering the last unfused abdominal ganglion (AG-7).
      Electrophysiological recordings of abdominal nerves demonstrated that females
      sense mechanical stimulation at their genital fold. The mechanosensory responses,
      however, were largely reduced by the insecticide pymetrozine that selectively
      blocks scolopidia of internal chordotonal organs but not campaniform and hair
      sensilla on the outer cuticle surface. In mating experiments, the females showed
      resistance behaviours towards males with asymmetrically shortened titillators,
      but the resistance was largely reduced when mechanoreceptors at the female's
      genital fold were either pharmacologically silenced by pymetrozine or
      mechanically blocked by capping with UV-hardened glue. Our findings support the
      hypothesis that the male titillators in these bushcrickets may serve as
      copulatory courtship devices to mechanically stimulate the female genitalia to
      reduce resistance behaviour.

PMID- 30111599
TI  - Phenotypic selection on floral traits in an urban landscape.
AB  - Native species are increasingly living in urban landscapes associated with
      abiotic and biotic changes that may influence patterns of phenotypic selection.
      However, measures of selection in urban and non-urban environments, and
      exploration of the mechanisms associated with such changes, are uncommon. Plant
      animal interactions have played a central role in the evolution of flowering
      plants and are sensitive to changes in the urban landscape, and thus provide
      opportunities to explore how urban environments modify selection. We evaluated
      patterns of phenotypic selection on the floral and resistance traits of Gelsemium
      sempervirens in urban and non-urban sites. The urban landscape had increased
      florivory and decreased pollen receipt, but showed only modest differences in
      patterns of selection. Directional selection for one trait, larger floral display
      size, was stronger in urban compared to non-urban sites. Neither quadratic nor
      correlational selection significantly differed between urban and non-urban sites.
      Pollination was associated with selection for larger floral display size in urban
      compared to non-urban sites, due to the differences in the translation of
      pollination into seeds rather than pollinator selectivity. Thus, our data suggest
      that urban landscapes may not result in sweeping differences in phenotypic
      selection but rather modest differences for some traits, potentially mediated by
      species interactions.

PMID- 30111601
TI  - Correction to: reply to Woodley of Menie et al.

PMID- 30111600
TI  - Before platelets: the production of platelet-activating factor during growth and
      stress in a basal marine organism.
AB  - Corals and humans represent two extremely disparate metazoan lineages and are
      therefore useful for comparative evolutionary studies. Two lipid-based molecules
      that are central to human immunity, platelet-activating factor (PAF) and Lyso-PAF
      were recently identified in scleractinian corals. To identify processes in corals
      that involve these molecules, PAF and Lyso-PAF biosynthesis was quantified in
      conditions known to stimulate PAF production in mammals (tissue growth and
      exposure to elevated levels of ultraviolet light) and in conditions unique to
      corals (competing with neighbouring colonies over benthic space). Similar to
      observations in mammals, PAF production was higher in regions of active tissue
      growth and increased when corals were exposed to elevated levels of ultraviolet
      light. PAF production also increased when corals were attacked by the stinging
      cells of a neighbouring colony, though only the attacked coral exhibited an
      increase in PAF. This reaction was observed in adjacent areas of the colony,
      indicating that this response is coordinated across multiple polyps including
      those not directly subject to the stress. PAF and Lyso-PAF are involved in coral
      stress responses that are both shared with mammals and unique to the ecology of
      cnidarians.

PMID- 30111602
TI  - Widespread use of emersion and cutaneous ammonia excretion in Aplocheiloid
      killifishes.
AB  - The invasion of land required amphibious fishes to evolve new strategies to avoid
      toxic ammonia accumulation in the absence of water flow over the gills. We
      investigated amphibious behaviour and nitrogen excretion strategies in six
      phylogenetically diverse Aplocheiloid killifishes (Anablepsoides hartii,
      Cynodonichthys hildebrandi, Rivulus cylindraceus, Kryptolebias marmoratus,
      Fundulopanchax gardneri, and Aplocheilus lineatus) in order to determine if a
      common strategy evolved. All species voluntarily emersed (left water) over
      several days, and also in response to environmental stressors (low O2, high
      temperature). All species were ammoniotelic in water and released gaseous ammonia
      (NH3 volatilization) during air exposure as the primary route for nitrogen
      excretion. Metabolic depression, urea synthesis, and/or ammonia accumulation
      during air exposure were not common strategies used by these species.
      Immunostaining revealed the presence of ammonia-transporting Rhesus proteins
      (Rhcg1 and Rhcg2) in the skin of all six species, indicating a shared mechanism
      for ammonia volatilization. We also found Rhcg in the skin of several other fully
      aquatic fishes, implying that cutaneous ammonia excretion is not exclusive to
      amphibious fishes. Overall, our results demonstrate that similar nitrogen
      excretion strategies while out of water were used by all killifish species
      tested; possibly the result of shared ancestral amphibious traits, phenotypic
      convergence, or a combination of both.

PMID- 30111603
TI  - The evolution of city life.
AB  - Urbanization represents a dominant and growing form of disturbance to Earth's
      natural ecosystems, affecting biodiversity and ecosystem services on a global
      scale. While decades of research have illuminated the effects of urban
      environmental change on the structure and function of ecological communities in
      cities, only recently have researchers begun exploring the effects of
      urbanization on the evolution of urban populations. The 15 articles in this
      special feature represent the leading edge of urban evolutionary biology and
      address existing gaps in our knowledge. These gaps include: (i) the absence of
      theoretical models examining how multiple evolutionary mechanisms interact to
      affect evolution in urban environments; (ii) a lack of data on how urbanization
      affects natural selection and local adaptation; (iii) poor understanding of
      whether urban areas consistently affect non-adaptive and adaptive evolution in
      similar ways across multiple cities; (iv) insufficient data on the genetic and
      especially genomic signatures of urban evolutionary change; and (v) limited
      understanding of the evolutionary processes underlying the origin of new human
      commensals. Using theory, observations from natural populations, common gardens,
      genomic data and cutting-edge population genomic and landscape genetic tools, the
      papers in this special feature address these gaps and highlight the power of
      urban evolutionary biology as a globally replicated 'experiment' that provides a
      powerful approach for understanding how human altered environments affect
      evolution.

PMID- 30111604
TI  - The onset of ecological diversification 50 years after colonization of a crater
      lake by haplochromine cichlid fishes.
AB  - Adaptive radiation research typically relies on the study of evolution in
      retrospective, leaving the predictive value of the concept hard to evaluate.
      Several radiations, including the cichlid fishes in the East African Great Lakes,
      have been studied extensively, yet no study has investigated the onset of the
      intraspecific processes of niche expansion and differentiation shortly after
      colonization of an adaptive zone by cichlids. Haplochromine cichlids of one of
      the two lineages that seeded the Lake Victoria radiation recently arrived in Lake
      Chala, a lake perfectly suited for within-lake cichlid speciation. Here, we infer
      the colonization and demographic history, quantify phenotypic, ecological and
      genomic diversity and diversification, and investigate the selection regime to
      ask if the population shows signs of diversification resembling the onset of
      adaptive radiation. We find that since their arrival in the lake, haplochromines
      have colonized a wide range of depth habitats associated with ecological and
      morphological expansion and the beginning of phenotypic differentiation and
      potentially nascent speciation, consistent with the very early onset of an
      adaptive radiation process. Moreover, we demonstrate evidence of rugged
      phenotypic fitness surfaces, indicating that current ecological selection may
      contribute to the phenotypic diversification.

PMID- 30111605
TI  - Temperature drives Zika virus transmission: evidence from empirical and
      mathematical models.
AB  - Temperature is a strong driver of vector-borne disease transmission. Yet, for
      emerging arboviruses we lack fundamental knowledge on the relationship between
      transmission and temperature. Current models rely on the untested assumption that
      Zika virus responds similarly to dengue virus, potentially limiting our ability
      to accurately predict the spread of Zika. We conducted experiments to estimate
      the thermal performance of Zika virus (ZIKV) in field-derived Aedes aegypti
      across eight constant temperatures. We observed strong, unimodal effects of
      temperature on vector competence, extrinsic incubation period and mosquito
      survival. We used thermal responses of these traits to update an existing
      temperature-dependent model to infer temperature effects on ZIKV transmission.
      ZIKV transmission was optimized at 29 degrees C, and had a thermal range of 22.7
      degrees C-34.7 degrees C. Thus, as temperatures move towards the predicted
      thermal optimum (29 degrees C) owing to climate change, urbanization or
      seasonality, Zika could expand north and into longer seasons. By contrast, areas
      that are near the thermal optimum were predicted to experience a decrease in
      overall environmental suitability. We also demonstrate that the predicted thermal
      minimum for Zika transmission is 5 degrees C warmer than that of dengue, and
      current global estimates on the environmental suitability for Zika are greatly
      over-predicting its possible range.

PMID- 30111606
TI  - Balancing selection and introgression of newt immune-response genes.
AB  - The importance of interspecific introgression as a source of adaptive variation
      is increasingly recognized. Theory predicts that beneficial genetic variants
      cross species boundaries easily even when interspecific hybridization is rare and
      gene flow is strongly constrained throughout the genome. However, it remains
      unclear whether certain classes of genes are particularly prone to adaptive
      introgression. Genes affected by balancing selection (BS) may constitute such a
      class, because forms of BS that favour novel, initially rare alleles, should
      facilitate introgression. We tested this hypothesis in hybridizing newts by
      comparing 13 genes with signatures of BS, in particular an excess of common non
      synonymous polymorphisms, to the genomic background (154 genes). Parapatric
      hybridizing taxa were less differentiated in BS candidate genes than more closely
      related allopatric lineages, while the opposite was observed in the control
      genes. Coalescent and forward simulations that explored neutral and BS scenarios
      under isolation and migration showed that processes other than differential gene
      flow are unlikely to account for this pattern. We conclude that BS, probably
      involving a form of novel allele advantage, promotes introgression. This
      mechanism may be a source of adaptively relevant variation in hybridizing species
      over prolonged periods.

PMID- 30111607
TI  - Intravascular large B-cell lymphoma: a chameleon with multiple faces and many
      masks.
AB  - Intravascular large B-cell lymphoma (IVLBCL) is a rare, clinically aggressive
      lymphoma entity characterized by an almost exclusive growth of large cells within
      the lumen of all sized blood vessels. The reasons for this peculiar localization
      of neoplastic cells are only partially understood. Clinically, in its classical
      variant, IVLBCL presents with many nonspecific signs and symptoms such as fever
      of unknown origin and involvement of the central nervous system and skin. Cases,
      which show disease limited to the skin, following extensive staging workup, are
      called cutaneous variants and show a better prognosis. In addition, a
      hemophagocytic variant associated with hemophagocytic syndrome and often with
      hepatosplenic involvement and cytopenia has been described. The classical and
      hemophagocytic variants are present mainly in western or Asian countries,
      respectively, although exceptions have been increasingly reported in both
      geographical areas. The cutaneous variant is mostly observed in western
      countries. Staging of IVLBCL is difficult and still not satisfactory. The often
      poor prognosis of this type of lymphoma has been substantially improved by
      immunochemotherapy, in particular with rituximab. Despite improved outcome, a
      significant proportion of patients relapse, in particular those with central
      nervous system manifestations. This review focuses on histopathological features,
      pathogenetic elements, presenting symptoms, clinical variants, disease
      progression, prognostic factors, therapeutic management, and the outcome of
      IVLBCL.

PMID- 30111608
TI  - Loss-of-function zinc finger mutation in the EGLN1 gene associated with
      erythrocytosis.

PMID- 30111609
TI  - Phase 1b study of obinutuzumab, ibrutinib, and venetoclax in relapsed and
      refractory chronic lymphocytic leukemia.
AB  - Targeted therapies including the engineered afucosylated anti-CD20 monoclonal
      antibody obinutuzumab, Bruton's tyrosine kinase inhibitor ibrutinib, and B-cell
      lymphoma protein 2 inhibitor venetoclax have demonstrated significant clinical
      activity in chronic lymphocytic leukemia (CLL) and, based on their complementary
      mechanisms, are ideal for combination. However, combining venetoclax with other
      active agents raises safety concerns, as it may increase the risk for tumor lysis
      syndrome. To minimize this risk, we designed and implemented a fixed-duration
      regimen using sequentially administered obinutuzumab followed by ibrutinib (cycle
      2) and venetoclax (cycle 3), for a total of fourteen 28-day cycles. This phase 1b
      study included 12 patients with relapsed or refractory CLL. We tested 3 dose
      levels of venetoclax and identified the doses of all 3 agents approved by the US
      Food and Drug Administration for use in the combination. Adverse events were
      consistent with known toxicities of the individual agents, with hematologic
      adverse events being most frequent. No clinically significant tumor lysis
      syndrome occurred. The overall response rate was 92% (95% confidence interval,
      62%-100%), with 42% (5/12) achieving a complete remission or complete remission
      with incomplete marrow recovery. There were 6 patients with no detectable CLL in
      both the blood and bone marrow at the end of treatment. We found this regimen to
      be safe and tolerable in CLL, and capable of inducing deep responses, justifying
      future study in our ongoing phase 2 cohorts of relapsed or refractory and
      treatment-naive patients, as well as larger phase 3 trials currently in planning.
      This trial was registered at www.clinicaltrials.gov as #NCT02427451.

PMID- 30111610
TI  - Prenatal biochemical screening and long term risk of maternal cardiovascular
      disease: population based cohort study.

PMID- 30111612
TI  - Saudi Arabia orders thousands of doctors and medical students to leave Canada
      within days.

PMID- 30111613
TI  - A Lipid Droplet-Associated Degradation System in Plants.

PMID- 30111614
TI  - Tic-Tac-Toe: How TIC and TOC Coordinate Getting Proteins across the Line.

PMID- 30111615
TI  - Correction for Agudo-Ibanez et al., "H-Ras Distribution and Signaling in Plasma
      Membrane Microdomains Are Regulated by Acylation and Deacylation Events".

PMID- 30111616
TI  - Why Cochrane should prioritise sharing data.

PMID- 30111611
TI  - Dropping in on lipid droplets: insights into cellular stress and cancer.
AB  - Lipid droplets (LD) have increasingly become a major topic of research in recent
      years following its establishment as a highly dynamic organelle. Contrary to the
      initial view of LDs being passive cytoplasmic structures for lipid storage,
      studies have provided support on how they act in concert with different
      organelles to exert functions in various cellular processes. Although lipid
      dysregulation resulting from aberrant LD homeostasis has been well characterised,
      how this translates and contributes to cancer progression is poorly understood.
      This review summarises the different paradigms on how LDs function in the
      regulation of cellular stress as a contributing factor to cancer progression.
      Mechanisms employed by a broad range of cancer cell types in differentially
      utilising LDs for tumourigenesis will also be highlighted. Finally, we discuss
      the potential of targeting LDs in the context of cancer therapeutics.

PMID- 30111618
TI  - Mapping Quantitative Trait Loci for Tolerance to Pythium irregulare in Soybean
      (Glycine max L.).
AB  - Pythium root rot is one of the significant diseases of soybean (Glycine max (L.)
      Merr.) in the United States. The causal agent of the disease is a soil-borne
      oomycete pathogen Pythium irregulare, the most prevalent and aggressive species
      of Pythium in North Central United States. However, few studies have been
      conducted in soybean for the identification of quantitative trait loci (QTL) for
      tolerance to P. irregulare In this study, two recombinant inbred line (RIL)
      populations (designated as POP1 and POP2) were challenged with P. irregulare
      (isolate CMISO2-5-14) in a greenhouse assay. POP1 and POP2 were derived from
      'E09014' * 'E05226-T' and 'E05226-T' * 'E09088', and contained 113 and 79 lines,
      respectively. Parental tests indicated that 'E05226-T' and 'E09014' were more
      tolerant than 'E09088', while 'E09088' was highly susceptible to the pathogen.
      The disease indices, root weight of inoculation (RWI) and ratio of root weight
      (RRW) of both populations showed near normal distributions, with transgressive
      segregation, suggesting the involvement of multiple QTL from both parents
      contributed to the tolerance. All the lines were genotyped using Illumina
      Infinium BARCSoySNP6K iSelect BeadChip and yielded 1373 and 1384 polymorphic
      markers for POP1 and POP2, respectively. Notably, despite high density,
      polymorphic markers coverage was incomplete in some genomic regions. As such, 28
      and 37 linkage groups were obtained in POP1 and POP2, respectively corresponding
      to the 20 soybean chromosomes. Using RRW, one QTL was identified in POP1 on
      Chromosome 20 that explained 12.7-13.3% of phenotypic variation. The desirable
      allele of this QTL was from 'E05226-T'. Another QTL was found in POP2 on
      Chromosome 11. It explained 15.4% of the phenotypic variation and the desirable
      allele was from 'E09088'. However, no QTL were identified using RWI in either
      population. These results supported that RRW was more suitable to be used to
      evaluate P. irregulare tolerance in soybean.

PMID- 30111619
TI  - Early Diverging Insect-Pathogenic Fungi of the Order Entomophthorales Possess
      Diverse and Unique Subtilisin-Like Serine Proteases.
AB  - Insect-pathogenic fungi use subtilisin-like serine proteases (SLSPs) to degrade
      chitin-associated proteins in the insect procuticle. Most insect-pathogenic fungi
      in the order Hypocreales (Ascomycota) are generalist species with a broad host
      range, and most species possess a high number of SLSPs. The other major clade of
      insect-pathogenic fungi is part of the subphylum Entomophthoromycotina
      (Zoopagomycota, formerly Zygomycota) which consists of high host-specificity
      insect-pathogenic fungi that naturally only infect a single or very few host
      species. The extent to which insect-pathogenic fungi in the order
      Entomophthorales rely on SLSPs is unknown. Here we take advantage of recently
      available transcriptomic and genomic datasets from four genera within
      Entomophthoromycotina: the saprobic or opportunistic pathogens Basidiobolus
      meristosporus, Conidiobolus coronatus, C. thromboides, C. incongruus, and the
      host-specific insect pathogens Entomophthora muscae and Pandora formicae,
      specific pathogens of house flies (Muscae domestica) and wood ants (Formica
      polyctena), respectively. In total 154 SLSP from six fungi in the subphylum
      Entomophthoromycotina were identified: E. muscae (n = 22), P. formicae (n = 6),
      B. meristosporus (n = 60), C. thromboides (n = 18), C. coronatus (n = 36), and C.
      incongruus (n = 12). A unique group of 11 SLSPs was discovered in the genomes of
      the obligate biotrophic fungi E. muscae, P. formicae and the saprobic human
      pathogen C. incongruus that loosely resembles bacillopeptidase F-like SLSPs.
      Phylogenetics and protein domain analysis show this class represents a unique
      group of SLSPs so far only observed among Bacteria, Oomycetes and early diverging
      fungi such as Cryptomycota, Microsporidia, and Entomophthoromycotina. This group
      of SLSPs is missing in the sister fungal lineages of Kickxellomycotina and the
      fungal phyla Mucoromyocta, Ascomycota and Basidiomycota fungi suggesting
      interesting gene loss patterns.

PMID- 30111620
TI  - Genomic Structural Variations Within Five Continental Populations of Drosophila
      melanogaster.
AB  - Chromosomal structural variations (SV) including insertions, deletions,
      inversions, and translocations occur within the genome and can have a significant
      effect on organismal phenotype. Some of these effects are caused by structural
      variations containing genes. Large structural variations represent a significant
      amount of the genetic diversity within a population. We used a global sampling of
      Drosophila melanogaster (Ithaca, Zimbabwe, Beijing, Tasmania, and Netherlands) to
      represent diverse populations within the species. We used long-read sequencing
      and optical mapping technologies to identify SVs in these genomes. Among the five
      lines examined, we found an average of 2,928 structural variants within these
      genomes. These structural variations varied greatly in size and location,
      included many exonic regions, and could impact adaptation and genomic evolution.

PMID- 30111617
TI  - Human lung development: recent progress and new challenges.
AB  - Recent studies have revealed biologically significant differences between human
      and mouse lung development, and have reported new in vitro systems that allow
      experimental manipulation of human lung models. At the same time, emerging
      clinical data suggest that the origins of some adult lung diseases are found in
      embryonic development and childhood. The convergence of these research themes has
      fuelled a resurgence of interest in human lung developmental biology. In this
      Review, we discuss our current understanding of human lung development, which has
      been profoundly influenced by studies in mice and, more recently, by experiments
      using in vitro human lung developmental models and RNA sequencing of human foetal
      lung tissue. Together, these approaches are helping to shed light on the
      mechanisms underlying human lung development and disease, and may help pave the
      way for new therapies.

PMID- 30111621
TI  - Accounting for Programmed Ribosomal Frameshifting in the Computation of Codon
      Usage Bias Indices.
AB  - Experimental evidence shows that synonymous mutations can have important
      consequences on genetic fitness. Many organisms display codon usage bias (CUB),
      where synonymous codons that are translated into the same amino acid appear with
      distinct frequency. Within genomes, CUB is thought to arise from selection for
      translational efficiency and accuracy, termed the translational efficiency
      hypothesis (TEH). Indeed, CUB indices correlate with protein expression levels,
      which is widely interpreted as evidence for translational selection. However,
      these tests neglect -1 programmed ribosomal frameshifting (-1 PRF), an important
      translational disruption effect found across all organisms of the tree of life.
      Genes that contain -1 PRF signals should cost more to express than genes without.
      Thus, CUB indices that do not consider -1 PRF may overestimate genes' true
      adaptation to translational efficiency and accuracy constraints. Here, we first
      investigate whether -1 PRF signals do indeed carry such translational cost. We
      then propose two corrections for CUB indices for genes containing -1 PRF signals.
      We retest the TEH in Saccharomyces cerevisiae under these corrections. We find
      that the correlation between corrected CUB index and protein expression remains
      intact for most levels of uniform -1 PRF efficiencies, and tends to increase when
      these efficiencies decline with protein expression. We conclude that the TEH is
      strengthened and that -1 PRF events constitute a promising and useful tool to
      examine the relationships between CUB and selection for translation efficiency
      and accuracy.

PMID- 30111622
TI  - Pheophorbide A: Fluorescent Bcrp Substrate to Measure Oral Drug-Drug Interactions
      in Real-Time In Vivo.
AB  - We investigated whether pheophorbide A (PhA) could serve as a selective breast
      cancer resistance protein (BCRP) substrate (victim) to screen in vivo using
      fluorescent live animal imaging for transporter-mediated interactions with orally
      administered inhibitors (perpetrators), and whether that could be coupled with
      serum sampling to measure the systemic concentration of PhA with a fast
      throughput in vitro fluorescent assay. PhA is a breakdown product of chlorophyll
      and is highly fluorescent in the near-infrared (NIR) spectrum. Whole-body NIR
      fluorescence was greater in the Bcrp KO compared with wild-type (WT) mice fed a
      regular diet containing chlorophyll and PhA, with fluorescence in WT mice
      confined to the intestine. PhA intestinal enterocyte fluorescence, after removing
      lumen contents, was greater in Bcrp knockout (KO) mice versus WT mice due to PhA
      enterocyte absorption and lack of PhA efflux by Bcrp. This difference was
      eliminated by maintaining the mice on an alfalfa (chlorophyll/PhA)-free diet. The
      area under the fluorescence ratio-time curve up to 6 hours (AUCFL 0-6 h) of
      orally administrated PhA was 3.5 times greater in the Bcrp KO mice compared with
      WT mice, and the PhA serum concentration was 50-fold higher in KO mice.
      Pretreatment with known BCRP inhibitors lapatinib, curcumin, elacridar,
      pantoprazole, and sorafenib, at clinically relevant doses, significantly
      increased PhA AUCFL 0-6 h by 2.4-, 2.3-, 2.2-, 1.5-, and 1.4-fold, respectively,
      whereas the area under PhA serum concentration-time curve calculated up to 6
      hours (AUCSerum 0-6 h) increased by 13.8-, 7.8-, 5.2-, 2.02-, and 1.45-fold,
      respectively, and corresponded to their hierarchy as in vitro BCRP inhibitors.
      Our results demonstrate that live animal imaging using PhA can be used to
      identify BCRP inhibitors and to assess the potential for BCRP-mediated clinical
      drug-drug interactions.

PMID- 30111623
TI  - How to Determine the Role of the Microbiome in Drug Disposition.
AB  - With a paradigm shift occurring in health care toward personalized and precision
      medicine, understanding the numerous environmental factors that impact drug
      disposition is of paramount importance. The highly diverse and variant nature of
      the human microbiome is now recognized as a factor driving interindividual
      variation in therapeutic outcomes. The purpose of this review is to provide a
      practical guide on methodology that can be applied to study the effects of
      microbes on the absorption, distribution, metabolism, and excretion of drugs. We
      also highlight recent examples of how these methods have been successfully
      applied to help build the basis for researching the intersection of the
      microbiome and pharmacology. Although in vitro and in vivo preclinical models are
      highlighted, these methods are also relevant in late-phase drug development or
      even as a part of routine after-market surveillance. These approaches will aid in
      filling major knowledge gaps for both current and upcoming therapeutics with the
      long-term goal of achieving a new type of knowledge-based medicine that
      integrates data on the host and the microbiome.

PMID- 30111624
TI  - Oligomerization and Catalytic Parameters of Human UDP-Glucuronosyltransferase
      1A10: Expression and Characterization of the Recombinant Protein.
AB  - UDP-glucuronosyltransferase (UGT), as an integral membrane protein localized in
      the endoplasmic reticulum, has the ability to detoxify potentially hazardous
      xenobiotic substances. Most UGTs are expressed in liver, but UGT1A10 has proven
      to be an extrahepatic enzyme considerably expressed throughout the
      gastrointestinal tract. Earlier studies indicated that different UGT isoforms
      could exist in higher-order homo-oligomers or at least dimers within the
      membrane, but the formation of intermolecular disulfide bridges between UGT
      molecules was not often observed. In this study, we expressed recombinant human
      UGT1A10 in human embryonic kidney (HEK)293 and Chinese hamster ovary (CHO) cells
      to examine its oligomeric states and characterize its enzymatic activities
      against two therapeutically interesting substrates, morphine and entacapone,
      including determination of the catalytic rate constant (kcat) values for the
      first time. It was observed that a majority of the UGT1A10 protein expressed in
      HEK293 cells existed in covalently crosslinked higher-order oligomers via
      formation of intermolecular disulfide bonds, whereas formation of the
      intermolecular disulfide bonds was not observed in the UGT1A10 protein expressed
      in CHO cells. Owing to the formation of the covalently crosslinked higher-order
      oligomers, the UGT1A10 protein expressed in HEK293 cells had much lower catalytic
      activity (particularly the catalytic rate constant kcat) against both morphine
      and entacapone, compared with the UGT1A10 protein form expressed in CHO cells
      against the same substrates.

PMID- 30111625
TI  - Models and Approaches Describing the Metabolism, Transport, and Toxicity of Drugs
      Administered by the Ocular Route.
AB  - The eye is a complex organ with a series of anatomic barriers that provide
      protection from physical and chemical injury while maintaining homeostasis and
      function. The physiology of the eye is multifaceted, with dynamic flows and
      clearance mechanisms. This review highlights that in vitro ocular transport and
      metabolism models are confined by the availability of clinically relevant
      absorption, distribution, metabolism, and excretion (ADME) data. In vitro ocular
      transport models used for pharmacology and toxicity poorly predict ocular
      exposure. Although ocular cell lines cannot replicate in vivo conditions, these
      models can help rank-order new chemical entities in discovery. Historic ocular
      metabolism of small molecules was assumed to be inconsequential or assessed using
      authentic standards. While various in vitro models have been cited, no single
      system is perfect, and many must be used in combination. Several studies document
      the use of laboratory animals for the prediction of ocular pharmacokinetics in
      humans. This review focuses on the use of human-relevant and human-derived models
      which can be utilized in discovery and development to understand ocular
      disposition of new chemical entities. The benefits and caveats of each model are
      discussed. Furthermore, ADME case studies are summarized retrospectively and
      capture the ADME data collected for health authorities in the absence of
      definitive guidelines. Finally, we discuss the novel technologies and a
      hypothesis-driven ocular drug classification system to provide a holistic
      perspective on the ADME properties of drugs administered by the ocular route.

PMID- 30111626
TI  - A Population-Based Surveillance Study of Shared Genotypes of Escherichia coli
      Isolates from Retail Meat and Suspected Cases of Urinary Tract Infections.
AB  - There is increasing evidence that retail food may serve as a source of
      Escherichia coli that causes community-acquired urinary tract infections, but the
      impact of this source in a community is not known. We conducted a prospective,
      population-based study in one community to examine the frequency of recovery of
      uropathogenic E. coli genotypes from retail meat samples. We analyzed E. coli
      isolates from consecutively collected urine samples of patients suspected to have
      urinary tract infections (UTIs) at a university-affiliated health service and
      retail meat samples from the same geographic region. We genotyped all E. coli
      isolates by multilocus sequence typing (MLST) and tested them for antimicrobial
      susceptibility. From 2016 to 2017, we cultured 233 E. coli isolates from 230
      (21%) of 1,087 urine samples and 177 E. coli isolates from 120 (28%) of 427
      retail meat samples. Urine samples contained 61 sequence types (STs), and meat
      samples had 95 STs; 12 STs (ST10, ST38, ST69, ST80, ST88, ST101, ST117, ST131,
      ST569, ST906, ST1844, and ST2562) were common to both. Thirty-five (81%) of 43
      meat isolates among the 12 STs were from poultry. Among 94 isolates in the 12
      STs, 26 (60%) of 43 retail meat isolates and 15 (29%) of 51 human isolates were
      pan-susceptible (P < 0.005). We found that 21% of E. coli isolates from suspected
      cases of UTIs belonged to STs found in poultry. Poultry may serve as a possible
      reservoir of uropathogenic E. coli (UPEC). Additional studies are needed to
      demonstrate transmission pathways of these UPEC genotypes and their food
      sources.IMPORTANCE Community-acquired urinary tract infection caused by
      Escherichia coli is one of the most common infectious diseases in the United
      States, affecting approximately seven million women and costing approximately
      11.6 billion dollars annually. In addition, antibiotic resistance among E. coli
      bacteria causing urinary tract infection continues to increase, which greatly
      complicates treatment. Identifying sources of uropathogenic E. coli and
      implementing prevention measures are essential. However, the reservoirs of
      uropathogenic E. coli have not been well defined. This study demonstrated that
      poultry sold in retail stores may serve as one possible source of uropathogenic
      E. coli This finding adds to a growing body of evidence that suggests that
      urinary tract infection may be a food-borne disease. More research in this area
      can lead to the development of preventive strategies to control this common and
      costly infectious disease.

PMID- 30111627
TI  - Aminoglycoside Heteroresistance in Acinetobacter baumannii AB5075.
AB  - Heteroresistance is a phenomenon where a subpopulation of cells exhibits higher
      levels of antibiotic resistance than the general population. Analysis of
      tobramycin resistance in Acinetobacter baumannii AB5075 using Etest strips
      demonstrated that colonies with increased resistance arose at high frequency
      within the zone of growth inhibition. The presence of a resistant subpopulation
      was confirmed by population analysis profiling (PAP). The tobramycin-resistant
      subpopulation was cross resistant to gentamicin but not amikacin. The increased
      tobramycin resistance phenotype was highly unstable, and cells reverted to a less
      resistant population at frequencies of 60 to 90% after growth on nonselective
      media. Furthermore, the frequency of the resistant subpopulation was not
      increased by preincubation with subinhibitory concentrations of tobramycin. The
      tobramycin-resistant subpopulation was shown to replicate during the course of
      antibiotic treatment, demonstrating that these were not persister cells. In A.
      baumannii AB5075, a large plasmid (p1AB5075) carries aadB, a 2"
      nucleotidyltransferase that confers resistance to both tobramycin and gentamicin
      but not amikacin. The aadB gene is part of an integron and is carried adjacent to
      four additional resistance genes that are all flanked by copies of an integrase
      gene. In isolates with increased resistance, this region was highly amplified in
      a RecA-dependent manner. However, in a recA mutant, colonies with unstable
      tobramycin resistance arose by a mechanism that did not involve amplification of
      this region. These data indicate that tobramycin heteroresistance occurs by at
      least two mechanisms in A. baumannii, and future studies to determine its effect
      on patient outcomes are warranted.IMPORTANCEAcinetobacter baumannii has become an
      important pathogen in hospitals worldwide, where the incidence of these
      infections has been increasing. A. baumannii infections have become exceedingly
      difficult to treat due to a rapid increase in the frequency of multidrug- and pan
      resistant isolates. This has prompted the World Health Organization to list A.
      baumannii as the top priority for the research and development of new
      antibiotics. This study reports for the first time a detailed analysis of
      aminoglycoside heteroresistance in A. baumannii We define the mechanistic basis
      for heteroresistance, where the aadB(ant2")Ia gene encoding an aminoglycoside
      adenylyltransferase becomes highly amplified in a RecA-dependent manner.
      Remarkably, this amplification of 20 to 40 copies occurs stochastically in 1/200
      cells in the absence of antibiotic selection. In addition, we provide evidence
      for a second RecA-independent mechanism for aminoglycoside heteroresistance. This
      study reveals that aminoglycoside resistance in A. baumannii is far more complex
      than previously realized and has important implications for the use of
      aminoglycosides in treating A. baumannii infections.

PMID- 30111630
TI  - Second Correction for Henson et al., "Artificial Seawater Media Facilitate
      Cultivating Members of the Microbial Majority from the Gulf of Mexico".

PMID- 30111628
TI  - Tongue Microbiota and Oral Health Status in Community-Dwelling Elderly Adults.
AB  - Tongue microbiota are a dominant source of oral microbial populations that are
      ingested with saliva, and therefore careful attention is required for the
      maintenance of health of elderly adults, who are susceptible to aspiration of
      oral contents. This study aimed to investigate the variation in tongue microbiota
      among community-dwelling elderly adults. Following a dental examination, tongue
      coating was collected from a 15-mm-diameter circular area at the center of the
      tongue dorsum of 506 elderly adults aged 70 to 80 years inhabiting the town of
      Hisayama, Japan. The microbial composition and density were determined by a 16S
      rRNA gene sequencing approach using a next-generation sequencer and quantitative
      PCR analysis, respectively. Co-occurrence network analysis identified two
      cohabiting groups of predominant commensals, one of which was primarily composed
      of Prevotella histicola, Veillonella atypica, Streptococcus salivarius, and
      Streptococcus parasanguinis; these organisms have been previously associated with
      an increased risk of mortality due to pneumonia in the frail elderly. This
      bacterial group was more predominant in the elderly with fewer teeth, a higher
      plaque index, and more dental caries experience, whereas the total bacterial
      density was independent of these traits. A higher density of fungi was also
      observed in the elderly with these traits, as well as in individuals who wore
      dentures. These results suggest that elderly adults with poorer oral health
      swallow a more dysbiotic microbiota formed on the tongue.IMPORTANCE Aspiration of
      oral contents can lead to pneumonia, which is a major cause of death among
      elderly adults susceptible to swallowing impairments. Tongue microbiota are a
      dominant source of oral microbial populations that are ingested with saliva. This
      large-scale population-based study revealed variations in the tongue microbiota
      among community-dwelling elderly adults. The total bacterial density was
      independent of the conditions of teeth surrounding the tongue, whereas the
      microbiota composition, especially the relative abundances of predominant
      commensals, showed an association with tooth conditions. Our results demonstrate
      that the elderly with fewer teeth, poorer dental hygiene, and more dental caries
      experience constantly ingest more dysbiotic microbiota, which could be harmful
      for their respiratory health.

PMID- 30111629
TI  - Staphylococcus aureus Biofilm Growth on Cystic Fibrosis Airway Epithelial Cells
      Is Enhanced during Respiratory Syncytial Virus Coinfection.
AB  - Staphylococcus aureus is a major cause of chronic respiratory infection in
      patients with cystic fibrosis (CF). We recently showed that Pseudomonas
      aeruginosa exhibits enhanced biofilm formation during respiratory syncytial virus
      (RSV) coinfection on human CF airway epithelial cells (AECs). The impact of
      respiratory viruses on other bacterial pathogens during polymicrobial infections
      in CF remains largely unknown. To investigate if S. aureus biofilm growth in the
      CF airways is impacted by virus coinfection, we evaluated S. aureus growth on CF
      AECs. Initial studies showed an increase in S. aureus growth over 24 h, and
      microscopy revealed biofilm-like clusters of bacteria on CF AECs. Biofilm growth
      was enhanced when CF AECs were coinfected with RSV, and this observation was
      confirmed with S. aureus CF clinical isolates. Apical conditioned medium from RSV
      infected cells promoted S. aureus biofilms in the absence of the host epithelium,
      suggesting that a secreted factor produced during virus infection benefits S.
      aureus biofilms. Exogenous iron addition did not significantly alter biofilm
      formation, suggesting that it is not likely the secreted factor. We further
      characterized S. aureus-RSV coinfection in our model using dual host-pathogen RNA
      sequencing, allowing us to observe specific contributions of S. aureus and RSV to
      the host response during coinfection. Using the dual host-pathogen RNA sequencing
      approach, we observed increased availability of nutrients from the host and
      upregulation of S. aureus genes involved in growth, protein translation and
      export, and amino acid metabolism during RSV coinfection.IMPORTANCE The airways
      of individuals with cystic fibrosis (CF) are commonly chronically infected, and
      Staphylococcus aureus is the dominant bacterial respiratory pathogen in CF
      children. CF patients also experience frequent respiratory virus infections, and
      it has been hypothesized that virus coinfection increases the severity of S.
      aureus lung infections in CF. We investigated the relationship between S. aureus
      and the CF airway epithelium and observed that coinfection with respiratory
      syncytial virus (RSV) enhances S. aureus biofilm growth. However, iron, which was
      previously found to be a significant factor influencing Pseudomonas aeruginosa
      biofilms during virus coinfection, plays a minor role in S. aureus coinfections.
      Transcriptomic analyses provided new insight into how bacterial and viral
      pathogens alter host defense and suggest potential pathways by which dampening of
      host responses to one pathogen may favor persistence of another in the CF
      airways, highlighting complex interactions occurring between bacteria, viruses,
      and the host during polymicrobial infections.

PMID- 30111631
TI  - IL-21 Selectively Protects CD62L+ NKT Cells and Enhances Their Effector Functions
      for Adoptive Immunotherapy.
AB  - T cells expressing CD19-specific chimeric Ag receptors (CARs) produce high
      remission rates in B cell lymphoma, but frequent disease recurrence and
      challenges in generating sufficient numbers of autologous CAR T cells necessitate
      the development of alternative therapeutic effectors. Valpha24-invariant NKTs
      have intrinsic antitumor properties and are not alloreactive, allowing for off
      the-shelf use of CAR-NKTs from healthy donors. We recently reported that CD62L+
      NKTs persist longer and have more potent antilymphoma activity than CD62L- cells.
      However, the conditions governing preservation of CD62L+ cells during NKT cell
      expansion remain largely unknown. In this study, we demonstrate that IL-21
      preserves this crucial central memory-like NKT subset and enhances its antitumor
      effector functionality. We found that following antigenic stimulation with alpha
      galactosylceramide, CD62L+ NKTs both expressed IL-21R and secreted IL-21, each at
      significantly higher levels than CD62L- cells. Although IL-21 alone failed to
      expand stimulated NKTs, combined IL-2/IL-21 treatment produced more NKTs and
      increased the frequency of CD62L+ cells versus IL-2 alone. Gene expression
      analysis comparing CD62L+ and CD62L- cells treated with IL-2 alone or IL-2/IL-21
      revealed that the latter condition downregulated the proapoptotic protein BIM
      selectively in CD62L+ NKTs, protecting them from activation-induced cell death.
      Moreover, IL-2/IL-21-expanded NKTs upregulated granzyme B expression and produced
      more TH1 cytokines, leading to enhanced in vitro cytotoxicity of nontransduced
      and anti-CD19-CAR-transduced NKTs against CD1d+ and CD19+ lymphoma cells,
      respectively. Further, IL-2/IL-21-expanded CAR-NKTs dramatically increased the
      survival of lymphoma-bearing NSG mice compared with IL-2-expanded CAR-NKTs. These
      findings have immediate translational implications for the development of NKT
      cell-based immunotherapies targeting lymphoma and other malignancies.

PMID- 30111632
TI  - Crystal Structure of the Labile Complex of IL-24 with the Extracellular Domains
      of IL-22R1 and IL-20R2.
AB  - Crystal structure of the ternary complex of human IL-24 with two receptors, IL
      22R1 and IL-20R2, has been determined at 2.15 A resolution. A crystallizable
      complex was created by a novel approach involving fusing the ligand with a
      flexible linker to the presumed low-affinity receptor, and coexpression of this
      construct in Drosophila S2 cells together with the presumed high-affinity
      receptor. This approach, which may be generally applicable to other multiprotein
      complexes with low-affinity components, was necessitated by the instability of IL
      24 expressed by itself in either bacteria or insect cells. Although IL-24
      expressed in Escherichia coli was unstable and precipitated almost immediately
      upon its refolding and purification, a small fraction of IL-24 remaining in the
      folded state was shown to be active in a cell-based assay. In the crystal
      structure presented here, we found that two cysteine residues in IL-24 do not
      form a predicted disulfide bond. Lack of structural restraint by disulfides,
      present in other related cytokines, is most likely reason for the low stability
      of IL-24. Although the contact area between IL-24 and IL-22R1 is larger than
      between the cytokine and IL-20R2, calculations show the latter interaction to be
      slightly more stable, suggesting that the shared receptor (IL-20R2) might be the
      higher-affinity receptor.

PMID- 30111633
TI  - Human Lymph Nodes Maintain TCF-1hi Memory T Cells with High Functional Potential
      and Clonal Diversity throughout Life.
AB  - Translating studies on T cell function and modulation from mouse models to humans
      requires extrapolating in vivo results on mouse T cell responses in lymphoid
      organs (spleen and lymph nodes [LN]) to human peripheral blood T cells. However,
      our understanding of T cell responses in human lymphoid sites and their relation
      to peripheral blood remains sparse. In this study, we used a unique human tissue
      resource to study human T cells in different anatomical compartments within
      individual donors and identify a subset of memory CD8+ T cells in LN, which
      maintain a distinct differentiation and functional profile compared with memory
      CD8+ T cells in blood, spleen, bone marrow, and lungs. Whole-transcriptome and
      high-dimensional cytometry by time-of-flight profiling reveals that LN memory
      CD8+ T cells express signatures of quiescence and self-renewal compared with
      corresponding populations in blood, spleen, bone marrow, and lung. LN memory T
      cells exhibit a distinct transcriptional signature, including expression of stem
      cell-associated transcription factors TCF-1 and LEF-1, T follicular helper cell
      markers CXCR5 and CXCR4, and reduced expression of effector molecules. LN memory
      T cells display high homology to a subset of mouse CD8+ T cells identified in
      chronic infection models that respond to checkpoint blockade immunotherapy.
      Functionally, human LN memory T cells exhibit increased proliferation to TCR
      mediated stimulation and maintain higher TCR clonal diversity compared with
      memory T cells from blood and other sites. These findings establish human LN as
      reservoirs for memory T cells with high capacities for expansion and diverse
      recognition and important targets for immunotherapies.

PMID- 30111634
TI  - Recent trends in life expectancy across high income countries: retrospective
      observational study.
AB  - OBJECTIVES: To assess whether declines in life expectancy occurred across high
      income countries during 2014-16, to identify the causes of death contributing to
      these declines, and to examine the extent to which these declines were driven by
      shared or differing factors across countries. DESIGN: Demographic analysis using
      aggregated data. SETTING: Vital statistics systems of 18 member countries of the
      Organisation for Economic Co-operation and Development. PARTICIPANTS: 18
      countries with high quality all cause and cause specific mortality data available
      in 2014-16. MAIN OUTCOME MEASURES: Life expectancy at birth, 0-65 years, and 65
      or more years and cause of death contributions to changes in life expectancy at
      birth. RESULTS: The majority of high income countries in the study experienced
      declines in life expectancy during 2014-15; of the 18 countries, 12 experienced
      declines in life expectancy among women and 11 experienced declines in life
      expectancy among men. The average decline was 0.21 years for women and 0.18 years
      for men. In most countries experiencing declines in life expectancy, these
      declines were predominantly driven by trends in older age (>=65 years) mortality
      and in deaths related to respiratory disease, cardiovascular disease, nervous
      system disease, and mental disorders. In the United States, declines in life
      expectancy were more concentrated at younger ages (0-65 years), and drug overdose
      and other external causes of death played important roles in driving these
      declines. CONCLUSIONS: Most of the countries that experienced declines in life
      expectancy during 2014-15 experienced robust gains in life expectancy during 2015
      16 that more than compensated for the declines. However, the United Kingdom and
      the United States appear to be experiencing stagnating or continued declines in
      life expectancy, raising questions about future trends in these countries.

PMID- 30111636
TI  - The Antinociceptive and Anti-Inflammatory Properties of the alpha7 nAChR Weak
      Partial Agonist p-CF3 N,N-diethyl-N'-phenylpiperazine.
AB  - Chronic pain and inflammatory diseases can be regulated by complex mechanisms
      involving alpha7 nicotinic acetylcholine receptors (nAChRs), making this subtype
      a promising drug target for anti-inflammatory therapies. Recent evidence suggests
      that suchtreatment of inflammatory pain may rely on metabotropic-like rather than
      ionotropic activation of the alpha7 receptor subtype in non-neuronal cells. We
      previously identified para-trifluoromethyl (p-CF3) N,N-diethyl-N'
      phenylpiperazinium (diEPP) iodide to be among the compounds classified as silent
      agonists, which are very weak alpha7 partial agonists that are able to induce
      positive allosteric modulator (PAM)-sensitive desensitization. Such drugs have
      been shown to selectively promote alpha7 ionotropic-independent functions.
      Therefore, we here further investigated the electrophysiological profile of p-CF3
      diEPP and its in vivo antinociceptive activity using Xenopus oocytes expressing
      alpha7, alpha4beta2, or alpha3beta4 nAChRs. The evoked currents confirmed p-CF3
      diEPP to be alpha7-selective with a maximal agonism 5% that of acetylcholine
      (ACh). Coapplication of p-CF3 diEPP with the type II PAM 4-naphthalene-1-yl
      3a,4,5,9b-tetrahydro-3-H-cyclopenta[c]quinoline-8-sulfonic acid amide (TQS)
      produced desensitization that could be converted to PAM-potentiated currents,
      which at a negative holding potential were up to 13-fold greater than ACh
      controls. Voltage-dependence experiments indicated that channel block may limit
      both control ACh and TQS-potentiated responses. Although no p-CF3 diEPP agonist
      activity was detected for the heteromeric nAChRs, it was a noncompetitive
      antagonist of these receptors. The compound displayed remarkable antihyperalgesic
      and antiedema effects in in vivo assays. The antinociceptive activity was dose
      and time dependent. The anti-inflammatory components were sensitive to the alpha7
      selective antagonist methyllycaconitine, which supports the idea that these
      effects are mediated by the alpha7 nAChR.

PMID- 30111637
TI  - Acute Unilateral Sacroiliitis Mimicking Infection on Magnetic Resonance Imaging
      with Response to Nonsteroidal Antiinflammatory Drugs: A Distinct Presentation of
      Spondyloarthritis?

PMID- 30111635
TI  - The Coumarin Glucoside, Esculin, Reveals Rapid Changes in Phloem-Transport
      Velocity in Response to Environmental Cues.
AB  - The study of phloem transport and its vital roles in long-distance communication
      and carbon allocation have been hampered by a lack of suitable tools that allow
      high-throughput, real-time studies. Esculin, a fluorescent coumarin glucoside, is
      recognized by Suc transporters, including AtSUC2, which loads it into the phloem
      for translocation to sink tissues. These properties make it an ideal tool for use
      in live-imaging experiments, where it acts as a surrogate for Suc. Here, we show
      that esculin is translocated with a similar efficiency to Suc and, because of its
      ease of application and detection, demonstrate that it is an ideal tool for in
      vivo studies of phloem transport. We used esculin to determine the effect of
      different environmental cues on the velocity of phloem transport. We provide
      evidence that fluctuations in cotyledon Suc levels influence phloem velocity
      rapidly, supporting the pressure-flow model of phloem transport. Under acute
      changes in light levels, the phloem velocity mirrored changes in the expression
      of AtSUC2 This observation suggests that under certain environmental conditions,
      transcriptional regulation may affect the abundance of AtSUC2 and thus regulate
      the phloem transport velocity.

PMID- 30111638
TI  - Measuring Disease Activity and Damage with Validated Metrics: A Systematic Review
      on Mortality and Damage in Systemic Lupus Erythematosus.
AB  - OBJECTIVE: To identify the effect of disease activity and damage, measured by
      validated indices, on mortality and damage accrual, in order to inform upcoming
      Canadian systemic lupus erythematosus (SLE) recommendations. METHODS: Following
      GRADE (Grading of Recommendations Assessment, Development and Evaluation)
      methodology to fill in evidence-to-decision tables to create recommendations for
      "minimal investigations needed to monitor SLE patients at baseline and subsequent
      visits," a systematic literature review was performed. The effect of disease
      activity and damage, measured by validated metrics, on mortality and damage was
      systematically reviewed, with metaanalyses performed when available. RESULTS: A
      title/abstract screen of 5599 articles identified 816 articles for full paper
      review, with 102 meeting inclusion criteria and 53 with extractable data. Thirty
      three articles describing outcomes related to disease activity and 20 articles
      related to damage were identified. Mortality was associated with higher SLE
      Disease Activity Index-2000 scores in 6 studies (HR 1.14, 95% CI 1.06-1.22) and
      higher Systemic Lupus International Collaborating Clinics/ACR Damage Index scores
      in 6 studies (HR 1.53, 95% CI 1.28-1.83). Higher SLE Activity Measure scores were
      associated with increased risk of damage in 3 studies (OR 1.06, 95% CI 1.04
      1.08). British Isles Lupus Assessment Group was associated with mortality in 1
      study with HR of 1.15. CONCLUSION: Active SLE disease and damage are associated
      with and predict greater mortality and damage. The use of validated disease
      activity and damage metrics is important in the assessment of disease activity
      and damage and will inform upcoming Canadian recommendations for the assessment
      of SLE.

PMID- 30111641
TI  - Julian Tudor Hart: visionary general practitioner who introduced the concept of
      the "inverse care law".

PMID- 30111639
TI  - Effect of the Inclusion of the Metacarpophalangeal Joints on the Wrist Magnetic
      Resonance Imaging Scoring System in Juvenile Idiopathic Arthritis.
AB  - OBJECTIVE: To extend the magnetic resonance imaging (MRI) score for assessment of
      wrist synovitis in juvenile idiopathic arthritis (JIA) by inclusion of the
      metacarpophalangeal (MCP) joints, and to compare the metric properties of the
      original and the extended score. METHODS: Wrist MRI of 70 patients with JIA were
      scored by 3 independent readers according to (1) the wrist component of the
      rheumatoid arthritis MRI synovitis score (comprising distal radioulnar,
      radiocarpal, and combined midcarpal and carpometacarpal joints); and (2) an
      extended score including the MCP joints. Thirty-eight patients had a 1-year MRI
      followup. The concordance between the readers [intraclass correlation coefficient
      (ICC), 95% limits of agreement (LOA), and weighted Cohen's kappa], correlations
      with clinical variables (Spearman's rho), and the sensitivity to change
      [standardized response mean (SRM)] were calculated for both scores. RESULTS: The
      interreader agreement was moderate for the original score (ICC 0.77; 95% CI 0.68
      0.84) and good for the extended score (ICC 0.86; 95% CI 0.80-0.91). Using 95%
      LOA, the aggregate score variability was less favorable with relatively wide LOA.
      Weighted Cohen's kappa of the individual joints indicated good agreement for the
      original score and good to excellent agreement for the extended score.
      Correlations with clinical variables reflecting disease activity improved for the
      extended score and its SRM was higher compared to that of the original score.
      CONCLUSION: The extended score showed better reliability, construct validity, and
      sensitivity to change than the original. Inclusion of the MCP joints should be
      considered for a more accurate assessment of disease activity and treatment
      efficacy in JIA.

PMID- 30111640
TI  - Rheumatological Assessment Is Important for Interstitial Lung Disease Diagnosis.
AB  - OBJECTIVE: Interstitial lung diseases (ILD) form a diverse group of parenchymal
      lung disorders. Currently, a multidisciplinary team (MDT) including
      pulmonologists, radiologists, and pathologists is the gold standard for ILD
      diagnosis. Recently, additional subtypes of connective tissue disease (CTD)-ILD
      with autoimmune features were defined, making the rheumatological assessment
      increasingly important. We aimed to assess the effect of adding a rheumatologist
      to the MDT for routine rheumatology assessment. METHODS: A prospective study that
      assessed newly diagnosed ILD patients by 2 parallel blinded arms; all patients
      were evaluated by both MDT (e.g., history, physical examination, blood tests,
      pulmonary function tests, and biopsies, if needed) and a rheumatologist (e.g.,
      history, physical examination, blood and serological tests). RESULTS: Sixty
      patients were assessed with the mean age of 67.3 +/- 12 years, 55% male, and 28%
      smokers. The rheumatological assessment reclassified 21% of the idiopathic
      pulmonary fibrosis as CTD. Moreover, the number of CTD-ILD with autoimmune
      features was increased by 77%. These included antineutrophil cytoplasmic antibody
      associated vasculitis, antisynthetase syndrome, and IgG4-related ILD.
      Retrospectively, rheumatological evaluation could have saved 7 bronchoscopies and
      1 surgical biopsy. CONCLUSION: Adding routine rheumatology assessments could
      significantly increase diagnostic accuracy and reduce invasive procedures.

PMID- 30111642
TI  - TGFbeta inhibition restores a regenerative response in acute liver injury by
      suppressing paracrine senescence.
AB  - Liver injury results in rapid regeneration through hepatocyte proliferation and
      hypertrophy. However, after acute severe injury, such as acetaminophen poisoning,
      effective regeneration may fail. We investigated how senescence may underlie this
      regenerative failure. In human acute liver disease, and murine models, p21
      dependent hepatocellular senescence was proportionate to disease severity and was
      associated with impaired regeneration. In an acetaminophen injury mouse model, a
      transcriptional signature associated with the induction of paracrine senescence
      was observed within 24 hours and was followed by one of impaired proliferation.
      In mouse genetic models of hepatocyte injury and senescence, we observed
      transmission of senescence to local uninjured hepatocytes. Spread of senescence
      depended on macrophage-derived transforming growth factor-beta1 (TGFbeta1)
      ligand. In acetaminophen poisoning, inhibition of TGFbeta receptor 1 (TGFbetaR1)
      improved mouse survival. TGFbetaR1 inhibition reduced senescence and enhanced
      liver regeneration even when delivered beyond the therapeutic window for treating
      acetaminophen poisoning. This mechanism, in which injury-induced senescence
      impairs liver regeneration, is an attractive therapeutic target for developing
      treatments for acute liver failure.

PMID- 30111643
TI  - KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor
      growth in mice.
AB  - Pharmacological inhibition of uncontrolled cell growth with small-molecule
      inhibitors is a potential strategy for treating glioblastoma multiforme (GBM),
      the most malignant primary brain cancer. We showed that the synthetic small
      molecule KHS101 promoted tumor cell death in diverse GBM cell models, independent
      of their tumor subtype, and without affecting the viability of noncancerous brain
      cell lines. KHS101 exerted cytotoxic effects by disrupting the mitochondrial
      chaperone heat shock protein family D member 1 (HSPD1). In GBM cells, KHS101
      promoted aggregation of proteins regulating mitochondrial integrity and energy
      metabolism. Mitochondrial bioenergetic capacity and glycolytic activity were
      selectively impaired in KHS101-treated GBM cells. In two intracranial patient
      derived xenograft tumor models in mice, systemic administration of KHS101 reduced
      tumor growth and increased survival without discernible side effects. These
      findings suggest that targeting of HSPD1-dependent metabolic pathways might be an
      effective strategy for treating GBM.

PMID- 30111644
TI  - Rapid and specific labeling of single live Mycobacterium tuberculosis with a dual
      targeting fluorogenic probe.
AB  - Tuberculosis (TB) remains a public health crisis and a leading cause of infection
      related death globally. Although in high demand, imaging technologies that enable
      rapid, specific, and nongenetic labeling of live Mycobacterium tuberculosis (Mtb)
      remain underdeveloped. We report a dual-targeting strategy to develop a small
      molecular probe (CDG-DNB3) that can fluorescently label single bacilli within 1
      hour. CDG-DNB3 fluoresces upon activation of the beta-lactamase BlaC, a hydrolase
      naturally expressed in Mtb, and the fluorescent product is retained through
      covalent modification of the Mtb essential enzyme decaprenylphosphoryl-beta-d
      ribose 2'-epimerase (DprE1). This dual-targeting probe not only discriminates
      live from dead Bacillus Calmette-Guerin (BCG) but also shows specificity for Mtb
      over other bacterial species including 43 nontuberculosis mycobacteria (NTM). In
      addition, CDG-DNB3 can image BCG phagocytosis in real time, as well as Mtb in
      patients' sputum. Together with a low-cost, self-driven microfluidic chip, we
      have achieved rapid labeling and automated quantification of live BCG. This
      labeling approach should find many potential applications for research toward TB
      pathogenesis, treatment efficacy assessment, and diagnosis.

PMID- 30111647
TI  - Correction to "Maternal-Fetal Disposition and Metabolism of Retrorsine in
      Pregnant Rats".

PMID- 30111646
TI  - A protective Langerhans cell-keratinocyte axis that is dysfunctional in
      photosensitivity.
AB  - Photosensitivity, or skin sensitivity to ultraviolet radiation (UVR), is a
      feature of lupus erythematosus and other autoimmune and dermatologic conditions,
      but the mechanistic underpinnings are poorly understood. We identify a Langerhans
      cell (LC)-keratinocyte axis that limits UVR-induced keratinocyte apoptosis and
      skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation.
      We show that the absence of LCs in Langerin-diphtheria toxin subunit A (DTA) mice
      leads to photosensitivity and that, in vitro, mouse and human LCs can directly
      protect keratinocytes from UVR-induced apoptosis. LCs express EGFR ligands and a
      disintegrin and metalloprotease 17 (ADAM17), the metalloprotease that activates
      EGFR ligands. Deletion of ADAM17 from LCs leads to photosensitivity, and UVR
      induces LC ADAM17 activation and generation of soluble active EGFR ligands,
      suggesting that LCs protect by providing activated EGFR ligands to keratinocytes.
      Photosensitive systemic lupus erythematosus (SLE) models and human SLE skin show
      reduced epidermal EGFR phosphorylation and LC defects, and a topical EGFR ligand
      reduces photosensitivity. Together, our data establish a direct tissue-protective
      function for LCs, reveal a mechanistic basis for photosensitivity, and suggest
      EGFR stimulation as a treatment for photosensitivity in lupus erythematosus and
      potentially other autoimmune and dermatologic conditions.

PMID- 30111645
TI  - Finding useful biomarkers for Parkinson's disease.
AB  - The recent advent of an "ecosystem" of shared biofluid sample biorepositories and
      data sets will focus biomarker efforts in Parkinson's disease, boosting the
      therapeutic development pipeline and enabling translation with real-world impact.

PMID- 30111651
TI  - Correction: Significance of MAD2 Expression to Mitotic Checkpoint Control in
      Ovarian Cancer Cells.

PMID- 30111648
TI  - Compensatory Expression of Nur77 and Nurr1 Regulates NF-kappaB-Dependent
      Inflammatory Signaling in Astrocytes.
AB  - Inflammatory activation of glial cells promotes loss of dopaminergic neurons in
      Parkinson disease. The transcription factor nuclear factor kappaB (NF-kappaB)
      regulates the expression of multiple neuroinflammatory cytokines and chemokines
      in activated glial cells that are damaging to neurons. Thus, inhibition of NF
      kappaB signaling in glial cells could be a promising therapeutic strategy for the
      prevention of neuroinflammatory injury. Nuclear orphan receptors in the NR4A
      family, including NR4A1 (Nur77) and NR4A2 (Nurr1), can inhibit the inflammatory
      effects of NF-kappaB, but no approved drugs target these receptors. Therefore, we
      postulated that a recently developed NR4A receptor ligand, 1,1bis (3'indolyl)
      1(pmethoxyphenyl) methane (C-DIM5), would suppress NF-kappaB-dependent
      inflammatory gene expression in astrocytes after treatment with 1-methyl-4-phenyl
      1, 2, 3, 6-tetrahydropyridine (MPTP) and the inflammatory cytokines interferon
      gamma and tumor necrosis factor alpha C-DIM5 increased expression of Nur77 mRNA
      and suppressed expression of multiple neuroinflammatory genes. C-DIM5 also
      inhibited the expression of NFkappaB-regulated inflammatory and apoptotic genes
      in quantitative polymerase chain reaction array studies and effected p65 binding
      to unique genes in chromatin immunoprecipitation next-generation sequencing
      experiments but did not prevent p65 translocation to the nucleus, suggesting a
      nuclear-specific mechanism. C-DIM5 prevented nuclear export of Nur77 in
      astrocytes induced by MPTP treatment and simultaneously recruited Nurr1 to the
      nucleus, consistent with known transrepressive properties of this receptor.
      Combined RNAi knockdown of Nur77 and Nurr1 inhibited the anti-inflammatory
      activity of C-DIM5, demonstrating that C-DIM5 requires these receptors to inhibit
      NF-kappaB. Collectively, these data demonstrate that NR4A1/Nur77 and NR4A2/Nurr1
      dynamically regulated inflammatory gene expression in glia by modulating the
      transcriptional activity of NF-kappaB.

PMID- 30111649
TI  - Intracellular Binding Site for a Positive Allosteric Modulator of the Dopamine D1
      Receptor.
AB  - The binding site for DETQ [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5
      (2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one], a
      positive allosteric modulator (PAM) of the dopamine D1 receptor, was identified
      and compared with the binding site for CID 2886111 [N-(6-tert-butyl-3-carbamoyl
      4,5,6,7-tetrahydro-1-benzothiophen-2-yl)pyridine-4-carboxamide], a reference D1
      PAM. From D1/D5 chimeras, the site responsible for potentiation by DETQ of the
      increase in cAMP in response to dopamine was narrowed down to the N-terminal
      intracellular quadrant of the receptor; arginine-130 in intracellular loop 2
      (IC2) was then identified as a critical amino acid based on a human/rat species
      difference. Confirming the importance of IC2, a beta2-adrenergic receptor
      construct in which the IC2 region was replaced with its D1 counterpart gained the
      ability to respond to DETQ. A homology model was built from the agonist-state
      beta2-receptor structure, and DETQ was found to dock to a cleft created by IC2
      and adjacent portions of transmembrane helices 3 and 4 (TM3 and TM4). When
      residues modeled as pointing into the cleft were mutated to alanine, large
      reductions in the potency of DETQ were found for Val119 and Trp123 (flanking the
      conserved DRY sequence in TM3), Arg130 (located in IC2), and Leu143 (TM4). The
      D1/D5 difference was found to reside in Ala139; changing this residue to
      methionine as in the D5 receptor reduced the potency of DETQ by approximately
      1000-fold. None of these mutations affected the activity of CID 2886111,
      indicating that it binds to a different allosteric site. When combined, DETQ and
      CID 2886111 elicited a supra-additive response in the absence of dopamine,
      implying that both PAMs can bind to the D1 receptor simultaneously.

PMID- 30111653
TI  - Enpp1 inhibits ectopic joint calcification and maintains articular chondrocytes
      by repressing hedgehog signaling.
AB  - The differentiated phenotype of articular chondrocytes of synovial joints needs
      to be maintained throughout life. Disruption of the articular cartilage,
      frequently associated with chondrocyte hypertrophy and calcification, is a
      central feature in osteoarthritis (OA). However, the molecular mechanisms whereby
      phenotypes of articular chondrocytes are maintained and pathological
      calcification is inhibited remain poorly understood. Recently, the ecto-enzyme
      Enpp1, a suppressor of pathological calcification, was reported to be decreased
      in joint cartilage with OA in both human and mouse, and Enpp1 deficiency causes
      joint calcification. Here, we found that hedgehog (Hh) signaling activation
      contributes to ectopic joint calcification in the Enpp1-/- mice. In the Enpp1-/-
      joints, Hh signaling was upregulated. Further activation of Hh signaling by
      removing the patched 1 gene in the Enpp1-/- mice enhanced ectopic joint
      calcification, whereas removing Gli2 partially rescued the ectopic calcification
      phenotype. In addition, reduction of Galphas in the Enpp1-/- mice enhanced joint
      calcification, suggesting that Enpp1 inhibits Hh signaling and chondrocyte
      hypertrophy by activating Galphas-PKA signaling. Our findings provide new
      insights into the mechanisms underlying Enpp1 regulation of joint integrity.

PMID- 30111655
TI  - A dual genetic tracing system identifies diverse and dynamic origins of cardiac
      valve mesenchyme.
AB  - In vivo genomic engineering is instrumental for studying developmental biology
      and regenerative medicine. Development of novel systems with more site-specific
      recombinases (SSRs) that complement with the commonly used Cre-loxP would be
      valuable for more precise lineage tracing and genome editing. Here, we introduce
      a new SSR system via Nigri-nox. By generating tissue-specific Nigri knock-in and
      its responding nox reporter mice, we show that the Nigri-nox system works
      efficiently in vivo by targeting specific tissues. As a new orthogonal system to
      Cre-loxP, Nigri-nox provides an additional control of genetic manipulation. We
      also demonstrate how the two orthogonal systems Nigri-nox and Cre-loxP could be
      used simultaneously to map the cell fate of two distinct developmental origins of
      cardiac valve mesenchyme in the mouse heart, providing dynamics of cellular
      contribution from different origins for cardiac valve mesenchyme during
      development. This work provides a proof-of-principle application of the Nigri-nox
      system for in vivo mouse genomic engineering. Coupled with other SSR systems,
      Nigri-nox would be valuable for more precise delineation of origins and cell
      fates during development, diseases and regeneration.

PMID- 30111656
TI  - Coupling of apical-basal polarity and planar cell polarity to interpret the Wnt
      signaling gradient in feather development.
AB  - Sensing a global directional cue to orient cell growth is crucial in tissue
      morphogenesis. An anterior-posterior gradient of Wnt signaling controls the
      helical growth of feather branches (barbs), and thus the formation of bilateral
      feathers. However, it remains unclear how the keratinocytes sense this gradient
      and orient barb growth. Here, we show that in chicken, owing to feather
      branching, the global Wnt gradient is subdivided into periodic barbs. Within each
      barb, the anterior barbule plate cells tilt before the posterior cells. The core
      planar cell polarity gene Prickle1 is involved, as knockdown of its expression
      resulted in no cell shape change and no barb tilting. Furthermore, perturbation
      of the Wnt gradient leads to diffusive Prickle1 expression and loss of barb
      orientation. Finally, the asymmetric distribution of Wnt6/Fzd10 is coordinated by
      the apical-basal polarity of the barbule plate keratinocytes, which is in turn
      regulated by the Par3/aPKC machinery. Our data elucidate a new mechanism through
      which the global Wnt signaling gradient is interpreted locally to construct
      complex spatial forms.

PMID- 30111654
TI  - Nodal signaling has dual roles in fate specification and directed migration
      during germ layer segregation in zebrafish.
AB  - During gastrulation, endodermal cells actively migrate to the interior of the
      embryo, but the signals that initiate and coordinate this migration are poorly
      understood. By transplanting ectopically induced endodermal cells far from the
      normal location of endoderm specification, we identified the inputs that drive
      internalization without the confounding influences of fate specification and
      global morphogenic movements. We find that Nodal signaling triggers an autocrine
      circuit for initiating endodermal internalization. Activation of the Nodal
      receptor directs endodermal specification through sox32 and also induces
      expression of more Nodal ligands. These ligands act in an autocrine fashion to
      initiate endodermal cell sorting. Our work defines an 'AND' gate consisting of
      sox32-dependent endodermal specification and Nodal ligand reception controlling
      endodermal cell sorting to the inner layer of the embryo at the onset of
      gastrulation.

PMID- 30111658
TI  - Genetic variations in the SNP rs850807 reflect a trade-off between autism and
      paranoia symptom expressions: a comment on Crespi et al. 2018.

PMID- 30111657
TI  - RARgamma is required for mesodermal gene expression prior to gastrulation in
      Xenopus.
AB  - The developing vertebrate embryo is exquisitely sensitive to retinoic acid (RA)
      concentration, particularly during anteroposterior patterning. In contrast to
      Nodal and Wnt signaling, RA was not previously considered to be an instructive
      signal in mesoderm formation during gastrulation. Here, we show in Xenopus that
      RARgamma is indispensable for the expression of early mesoderm markers and is,
      therefore, an obligatory factor in mesodermal competence and/or maintenance. We
      identified several novel targets upregulated by RA receptor signaling in the
      early gastrula that are expressed in the circumblastoporal ring and linked to
      mesodermal development. Despite overlapping expression patterns of the genes
      encoding the RA-synthesizing enzyme Aldh1a2 and the RA-degrading enzyme Cyp26a1,
      RARgamma1 functions as a transcriptional activator in early mesoderm development,
      suggesting that RA ligand is available to the embryo earlier than previously
      appreciated. RARgamma1 is required for cellular adhesion, as revealed by
      spontaneous dissociation and depletion of ncam1 mRNA in animal caps harvested
      from RARgamma1 knockdown embryos. RARgamma1 knockdown obliterates somite
      boundaries, and causes loss of Myod protein in the presomitic mesoderm, but
      ectopic, persistent expression of Myod protein in the trunk. Thus, RARgamma1 is
      required for stabilizing the mesodermal fate, myogenic commitment, somite
      boundary formation, and terminal skeletal muscle differentiation.

PMID- 30111659
TI  - Special delivery: scavengers direct seed dispersal towards ungulate carcasses.
AB  - Cadaver decomposition islands around animal carcasses can facilitate
      establishment of various plant life. Facultative scavengers have great potential
      for endozoochory, and often aggregate around carcasses. Hence, they may disperse
      plant seeds that they ingest across the landscape towards cadaver decomposition
      islands. Here, we demonstrate this novel mechanism along a gradient of wild
      tundra reindeer carcasses. First, we show that the spatial distribution of
      scavenger faeces (birds and foxes) was concentrated around carcasses. Second,
      faeces of the predominant scavengers (corvids) commonly contained viable seeds of
      crowberry, a keystone species of the alpine tundra with predominantly vegetative
      reproduction. We suggest that cadaver decomposition islands function as endpoints
      for directed endozoochory by scavengers. Such a mechanism could be especially
      beneficial for species that rely on small-scale disturbances in soil and
      vegetation, such as several Nordic berry-producing species with cryptic
      generative reproduction.

PMID- 30111660
TI  - Paranoia, autism and the architecture of genomic conflicts: a reply to Abu-Akel
      2018.

PMID- 30111661
TI  - Synthesizing and tuning stochastic chemical reaction networks with specified
      behaviours.
AB  - Methods from stochastic dynamical systems theory have been instrumental in
      understanding the behaviours of chemical reaction networks (CRNs) arising in
      natural systems. However, considerably less attention has been given to the
      inverse problem of synthesizing CRNs with a specified behaviour, which is
      important for the forward engineering of biological systems. Here, we present a
      method for generating discrete-state stochastic CRNs from functional
      specifications, which combines synthesis of reactions using satisfiability modulo
      theories and parameter optimization using Markov chain Monte Carlo. First, we
      identify candidate CRNs that have the possibility to produce correct computations
      for a given finite set of inputs. We then optimize the parameters of each CRN,
      using a combination of stochastic search techniques applied to the chemical
      master equation, to improve the probability of correct behaviour and rule out
      spurious solutions. In addition, we use techniques from continuous-time Markov
      chain theory to analyse the expected termination time for each CRN. We illustrate
      our approach by synthesizing CRNs for probabilistically computing majority,
      maximum and division, producing both known and previously unknown networks,
      including a novel CRN for probabilistically computing the maximum of two species.
      In future, synthesis techniques such as these could be used to automate the
      design of engineered biological circuits and chemical systems.

PMID- 30111662
TI  - Influence of the windlass mechanism on arch-spring mechanics during dynamic foot
      arch deformation.
AB  - The function of the human foot is described dichotomously as a compliant
      structure during mid-stance and a stiff lever during push-off. The arch-spring
      and the windlass mechanisms, respectively, describe each of these behaviours;
      however, their interaction has not been quantified to date. We hypothesized that
      by engaging the windlass mechanism with metatarsophalangeal joint (MTPJ)
      dorsiflexion, we would observe stiffening of the arch and reduced energy
      absorption and dissipation during dynamic compressions of the foot. Using a
      custom apparatus, the MTPJ angle was fixed at 30 degrees of plantarflexion,
      neutral or 30 degrees of dorsiflexion for nine participants, with the shank
      positioned similarly to the end of mid-stance. The arch was compressed at two
      speeds, with the faster speed comparable to walking around 1.5 m s-1 Six cameras
      captured the compression and elongation of the arch, along with other kinematic
      variables, synchronously with the ground reaction force. Combining these
      measures, we computed the energy absorbed, returned and dissipated in the arch.
      Contrary to our hypothesis, when the windlass mechanism was engaged, the arch
      elongated more, and absorbed and dissipated more energy than when it was not
      engaged. This engagement of the windlass altered the rotational axis of the mid
      foot, which probably oriented the arch-spanning structures closer to their
      resting length, increasing their compliance. This study provides novel evidence
      for an interplay between the windlass and arch-spring mechanisms that aids in
      regulation of energy storage within the foot.

PMID- 30111663
TI  - Oxygen diffusion in ellipsoidal tumour spheroids.
AB  - Oxygen plays a central role in cellular metabolism, in both healthy and tumour
      tissue. The presence and concentration of molecular oxygen in tumours has a
      substantial effect on both radiotherapy response and tumour evolution, and as a
      result the oxygen micro-environment is an area of intense research interest.
      Multi-cellular tumour spheroids closely mimic real avascular tumours, and in
      particular they exhibit physiologically relevant heterogeneous oxygen
      distribution. This property has made them a vital part of in vitro
      experimentation. For ideal spheroids, their heterogeneous oxygen distributions
      can be predicted from theory, allowing determination of cellular oxygen
      consumption rate (OCR) and anoxic extent. However, experimental tumour spheroids
      often depart markedly from perfect sphericity. There has been little
      consideration of this reality. To date, the question of how far an ellipsoid can
      diverge from perfect sphericity before spherical assumptions break down remains
      unanswered. In this work, we derive equations governing oxygen distribution (and,
      more generally, nutrient and drug distribution) in both prolate and oblate tumour
      ellipsoids, and quantify the theoretical limits of the assumption that the
      spheroid is a perfect sphere. Results of this analysis yield new methods for
      quantifying OCR in ellipsoidal spheroids, and how this can be applied to markedly
      increase experimental throughput and quality.

PMID- 30111664
TI  - Drawing power of virtual crowds.
AB  - In 1969, social psychologist Milgram and his colleagues conducted an experiment
      on a busy city street where passers-by witnessed a set of actors spontaneously
      looking up towards a building. The experiment showed that the crowd's propensity
      to mimic the actor's gaze increased with the number of actors that looked up.
      This form of behavioural contagion is found in many social organisms and is
      central to how information travels through large groups. With the advancement of
      virtual reality and its continued application towards understanding human
      response to crowd behaviour, it remains to be verified if behavioural contagion
      occurs in walkable virtual environments, and how it compares with results from
      real-world experiments. In this study, we adapt Milgram's experiment for virtual
      environments and use it to reproduce behavioural contagion. Specifically, we
      construct a replica of an indoor location and combine two established pedestrian
      motion models to create an interactive crowd of 60 virtual characters that walk
      through the indoor location. The stimulus group comprised a subset of the
      characters who look up at a random time as the participants explore the virtual
      environment. Our results show that the probability of looking up by a participant
      is dependent on the size of the stimulus group saturating to near certainty when
      three or more characters look up. The role of stimulus size was also evident when
      participant actions were compared with survey responses which showed that more
      participants selected to not look up even though they saw characters redirect
      their gaze upwards when the size of the stimulus group was small. Participants
      also spent more time looking up and exhibited frequent head turns with a larger
      stimulus group. Results from this study provide evidence that behavioural
      contagion can be triggered in the virtual environment, and can be used to build
      and test complex hypotheses for understanding human behaviour in a variety of
      crowd scenarios.

PMID- 30111665
TI  - Understanding diseases as increased heterogeneity: a complex network
      computational framework.
AB  - Owing to the complexity of the human body, most diseases present a high
      interpersonal variability in the way they manifest, i.e. in their phenotype,
      which has important clinical repercussions-for instance, the difficulty in
      defining objective diagnostic rules. Here we explore the hypothesis that signs
      and symptoms used to define a disease should be understood in terms of the
      dispersion (as opposed to the average) of physical observables. To that end, we
      propose a computational framework, based on complex networks theory, to map
      groups of subjects to a network structure, based on their pairwise phenotypical
      similarity. We demonstrate that the resulting structure can be used to improve
      the performance of classification algorithms, especially in the case of a limited
      number of instances, with both synthetic and real datasets. Beyond providing an
      alternative conceptual understanding of diseases, the proposed framework could be
      of special relevance in the growing field of personalized, or N-to-1, medicine.

PMID- 30111666
TI  - Convex skeletons of complex networks.
AB  - A convex network can be defined as a network such that every connected induced
      subgraph includes all the shortest paths between its nodes. A fully convex
      network would therefore be a collection of cliques stitched together in a tree.
      In this paper, we study the largest high-convexity part of empirical networks
      obtained by removing the least number of edges, which we call a convex skeleton.
      A convex skeleton is a generalization of a network spanning tree in which each
      edge can be replaced by a clique of arbitrary size. We present different
      approaches for extracting convex skeletons and apply them to social collaboration
      and protein interactions networks, autonomous systems graphs and food webs. We
      show that the extracted convex skeletons retain the degree distribution,
      clustering, connectivity, distances, node position and also community structure,
      while making the shortest paths between the nodes largely unique. Moreover, in
      the Slovenian computer scientists coauthorship network, a convex skeleton retains
      the strongest ties between the authors, differently from a spanning tree or high
      betweenness backbone and high-salience skeleton. A convex skeleton thus
      represents a simple definition of a network backbone with applications in
      coauthorship and other social collaboration networks.

PMID- 30111668
TI  - Ketone Bodies Are an Alternative Energy Source and Exert Antioxidant Effects.

PMID- 30111667
TI  - Design, Synthesis and Screening of 4,6-Diaryl Pyridine and Pyrimidine Derivatives
      as Potential Cytotoxic Molecules.
AB  - A new series of pyridine and pyrimidine derivatives is designed and synthesized
      as potential antitumor molecules. The tested compounds show promising in vitro
      cytotoxic activity against HL-60 cell line as eight compounds: 4, 6, 11, 13, 14,
      15, 18 and 21 exhibit potent cytotoxic activity in sub-micromolar concentration
      higher than the combretastatin A4 (CA-4). Compound 21 shows a cytotoxic activity
      5-fold more potent than CA-4 on HL-60 cells. DNA-Flow cytometry cell cycle
      analysis and annexin-V assay on HL-60 cells show that compounds 4, 18 and 21
      exhibit potent cell growth inhibition, cell cycle arrest at G2/M phase and pro
      apoptotic inducing activities. The percentage inhibition assay of beta-tubulin
      polymerization on HL-60 cells shows that the antitumor activity of the tested
      compounds appears to correlate well with its ability to inhibit beta-tubulin
      polymerization. In addition, enzyme-linked immunosorbene assay (ELlSA)
      measurement for compound 21 shows apoptotic inducing activities through
      significant up regulation of p53, Bax/Bcl-2 ratio and caspase-3 proteins parallel
      to down regulation of the level of survivin proteins.

PMID- 30111669
TI  - Circulating Aminoterminal Propeptide of Type III Procollagen as a Biomarker of
      Cardiovascular Events in Patients Undergoing Hemodialysis.
AB  - AIM: Type III collagen abundantly exists in the cardiovascular system, including
      the aorta and heart. We prospectively investigated whether serum levels of
      aminoterminal propeptide of type III procollagen (PIIINP), a circulating
      biomarker of cardiovascular fibrosis, could predict cardiovascular events in
      patients undergoing hemodialysis. METHODS: Serum PIIINP concentrations were
      measured in 244 patients undergoing maintenance hemodialysis (men, 126; women,
      118; mean age, 64+/-11 years; dialysis duration, 11.5+/-7.8 years) by
      immunoradiometric assay in February 2005. The endpoint was cardiovascular events,
      and the patients were followed up until the endpoint was reached, or until
      January 31, 2011. RESULTS: During the follow-up for 4.7+/-1.8 years,
      cardiovascular events occurred in 78 (30.3%) of 244 patients. Stepwise Cox hazard
      analysis revealed that cardiovascular events were associated with increased serum
      PIIINP concentration (1 U/mL; hazard ratio, 1.616; P=0.0001). The median serum
      PIIINP concentrations were higher in patients with cardiovascular events than in
      those without (2.30+/-0.19 U/mL vs 1.30+/-0.03 U/mL; P<0.0001). When the patients
      were assigned to subgroups based on serum PIIINP cut-off value for cardiovascular
      events of 1.75 U/mL, defined by receiver operating characteristic analysis,
      cardiovascular event-free survival rates at 5 years were lower (P=0.0001) in the
      subgroup of serum PIIINP >=1.75 U/mL than in that of serum PIIINP <1.75 U/mL
      (31.9% vs 88.2%). CONCLUSIONS: Serum PIIINP could be a new biomarker for
      predicting the cardiovascular events in patients undergoing hemodialysis.

PMID- 30111670
TI  - Clusterin is highly expressed in tubular complexes during spontaneous
      pancreatitis of spontaneous hypertensive rats.
AB  - Pancreatitis is an inflammatory disorder of pancreas which leads to varying
      degrees of pancreatic endocrine and exocrine dysfunction and manifests in either
      acute or chronic forms. Spontaneous pancreatitis in experimental animals has
      rarely been reported. Here, we found acute to chronic courses of spontaneous
      pancreatitis in spontaneously hypertensive rats (SHRs), showing the formation of
      tubular complexes (TCs) and enhanced islet regeneration. We investigated the
      expression pattern of clusterin in the pancreas of SHRs based on
      immunohistochemistry (IHC). IHC analysis revealed the strong expression of
      clusterin in dedifferentiated duct-like cells and regenerative islets of TCs.
      These results imply that clusterin might be involved in the formation of TCs and
      parenchymal regeneration during rat pancreatitis.

PMID- 30111672
TI  - Changes in lectin-binding patterns in the kidneys of canines with immune-complex
      mediated glomerulonephritis.
AB  - We surveyed the kidneys of dogs with immune-complex mediated glomerulonephritis
      (ICGN) by lectin histochemistry using seven lectins-namely WGA, RCA-I, ConA, PNA,
      SBA, DBA, and UEA-I. Their binding patterns were compared with those from normal
      dogs. RCA-I signals became weak in the brush borders of the proximal tubules,
      whereas DBA signals became positive in Bowman's capsules. Also, varying intensity
      of the UEA-I signal was noted in the distal tubules, especially in the macula
      densa. The binding pattern profiles varied among the cases; this diversity in the
      lectin-binding patterns might be induced as a result of the diverse pathologies
      seen in canine ICGN.

PMID- 30111671
TI  - Neuromastoma of the hard palate mucosa in an Australian green tree frog (Litoria
      caerulea).
AB  - A hard palate mass was surgically removed from an Australian green tree frog
      (Litoria caerulea) and examined pathologically. The tumor consisted of sheets of
      small cells arranged in a tubular structure and cords or rosettes with
      fibrovascular stroma. Immunohistochemically, neoplastic cells were diffusely
      positive for cytokeratin and neuron-specific enolase and partially positive for S
      100 and doublecortin. These findings indicate that the tumor originated from the
      neuroectodermal tissue. Based on these findings, the tumor was classified as a
      neuromastoma (neuroepithelioma). Sensory cells located in the hard palate of the
      frog were considered to be the origin of the tumor. The frog died after going
      through 3 surgeries and experiencing difficulties closing its mouth.

PMID- 30111674
TI  - Early Relowering of Serum Sodium Concentration Overcomes Disturbances in
      Consciousness during Hyponatremia Overcorrection and Prevents Osmotic
      Demyelination Syndrome.
AB  - A 79-year-old woman without any cerebral hernia symptoms was hospitalized with
      hyponatremia. After syndrome of inappropriate antidiuretic hormone induced by
      drugs was diagnosed and water restriction implemented, the patient became
      comatose during overcorrection caused by the generation of a large volume of
      electrolyte-free urine. Once the serum sodium concentration was immediately
      relowered by the administration of desmopressin and 5% glucose solution, the
      patient's level of consciousness improved dramatically without osmotic
      demyelination syndrome (ODS) developing. This outcome suggests that, similar to
      the findings in rat models, relowering the serum sodium concentration as early as
      possible to counter a disturbance of consciousness during the overcorrection of
      hyponatremia prevents ODS.

PMID- 30111675
TI  - p-Toluenesulfonic Acid-based Deep Eutectic Solvent as Transesterification
      Catalyst for Biodiesel Production.
AB  - In this study, acidic deep eutectic solvents (DESs) have been studied as catalyst
      in transesterification of soybean oil with methanol to produce biodiesel. p
      Toluenesulfonic acid-based deep eutectic solvent (P-DES), composed of p
      toluenesulfonic acid and choline chloride (1:3, mol/mol), was found to be an
      efficient transesterification catalyst for biodiesel production. The optimum
      conditions for the transesterification process were as follows: 8% P-DES
      catalyst, 8:1 molar ratio of methanol to oil, reaction temperature of 110 degrees
      C and 2 h reaction time. The transesterification yield could reach 98.66+/-0.17%.
      And the P-DES exhibited as a heterogeneous catalyst after the reaction, which
      could be separated easily. And P-DES could remove the trace amount of by-product
      (glycerol) in the final biodiesel product, making this process more simple and
      cleaner.

PMID- 30111673
TI  - Bactericidal efficacy of a quaternary ammonium compound with food additive grade
      calcium hydroxide toward Salmonella Infantis and Escherichia coli on abiotic
      carriers.
AB  - The bactericidal efficacies of 0.2% food additive grade calcium hydroxide
      (FdCa(OH)2) solution, a quaternary ammonium compound (QAC) diluted at 1:500
      (QACx500) and their mixture-Mix500 (FdCa(OH)2 powder added at final concentration
      0.2% to QACx500)-were investigated at two different temperatures (room
      temperature (RT) (25 +/- 2 degrees C) and 2 degrees C), using varying contact
      time, with or without presence of organic materials (5% fetal bovine serum: FBS),
      either in suspension or on abiotic carrier (steel, rubber and plastic). In the
      suspension test, QACx500 could inactivate Salmonella Infantis at effective level
      (>=3 log reductions), within 30 sec and 5 sec, respectively, with or without 5%
      FBS at RT; however, at 2 degrees C it required 30 min and 1 min, respectively.
      Mix500 revealed the same efficacy as QACx500 at RT, but, at 2 degrees C it
      required 1 min and 30 sec, respectively with or without FBS. Whereas, 0.2%
      FdCa(OH)2 solution alone could inactivate S. Infantis within 1 min and 3 min,
      respectively at RT and 2 degrees C, even with 5% FBS. In the carrier test, single
      disinfectant required bit more (3 or 5 min) contact time to reduce bacterial load
      (S. Infantis or Escherichia coli) down to the effective level on rubber surface
      than that on steel and plastic surface. However, Mix500 could inactivate both
      bacteria on carrier surfaces within 1 min, even at 2 degrees C. Thus, synergistic
      effects were observed in the suspension test and the carrier test at both
      temperatures toward both bacteria.

PMID- 30111677
TI  - Tactile Texture of Cosmetic Sponges and Their Friction Behavior under Accelerated
      Movement.
AB  - We evaluated the friction properties of five cosmetic sponges on artificial skin
      using sinusoidal motion-friction evaluation system. No significant difference was
      observed in the pleasant score of the five sponges when these sponges were rubbed
      on the skin surface. The sponges were classified into three groups based on their
      tactile feel. Their characteristic tactile textures were moist-soft-slippery,
      moist-dry-rough, and moist feels. The slippery feel was found to depend on the
      thickness of the sponge's cell wall, its surface tension, and the change in
      friction coefficient in the dynamic friction process. These findings are useful
      in the design of cosmetic sponges.

PMID- 30111676
TI  - Efficient Detection of Edible Oils Adulterated with Used Frying Oils through PE
      film-based FTIR Spectroscopy Combined with DA and PLS.
AB  - Edible oil adulteration has been a considerable problem worldwide, and rapid
      detection methods should be established. In this study, a validation method for
      edible oil adulterated with used frying oil (UFO) was introduced through Fourier
      transform infrared (FTIR) spectroscopy. The spectral region of 6000-400 cm-1 was
      determined through FTIR by using a disposable polyethylene film, and absorption
      profiles at 1550-650 cm-1 region could be used for detection analysis. A
      qualitative analysis model was established through discriminant analysis, and
      edible oil adulteration with more than 1% content of UFO could be qualitatively
      analyzed. A quantitative analysis model was also created through partial least
      squares regression. When the actual value was more than 1.5%, the predicted and
      actual values showed good linear correlation. FTIR coupled with chemometric
      analysis is a useful tool to detect edible oil adulteration.

PMID- 30111678
TI  - Dietary Sparassis crispa Reduces Body Fat Mass and Hepatic Lipid Levels by
      Enhancing Energy Expenditure and Suppressing Lipogenesis in Rats.
AB  - Accumulation of abdominal fat triggers metabolic syndrome, which is a cluster of
      metabolic abnormalities, such as dyslipidemia, glucose intolerance, insulin
      resistance or hyperinsulinemia, and hypertension, that leads to the development
      of diabetes and cardiovascular disease. Mushrooms have been used as a foodstuff
      and folk medicine worldwide. Among these mushrooms, Sparassis crispa (SC) is a
      relatively newly cultivated edible and medicinal mushroom, which has been
      reported to have anti-diabetic and anti-hypertensive properties. However, little
      is known about the anti-obesity and anti-hyperlipidemic properties of SC. In the
      present study, we investigated the effects of dietary SC on lipid metabolism and
      energy expenditure in Sprague-Dawley rats with diet-induced obesity and diabetes,
      and conducted respiratory gas analysis to determine how energy metabolism is
      altered by SC. After feeding periods of 3 and 7 weeks, dietary SC had
      significantly reduced hepatic triacylglycerol and cholesterol contents in a dose
      dependent manner. These changes were attributable to suppression of fatty acid
      and cholesterol synthesis in the liver and increased insulin sensitivity in the
      body. In addition, after a feeding period of 6 weeks, dietary SC significantly
      increased energy expenditure through carbohydrate oxidation, reducing abdominal
      fat mass after 7 weeks. In conclusion, our results indicate that in addition to
      the previously reported anti-diabetic and anti-hypertensive activities, dietary
      SC exhibits anti-obesity and anti-hyperlipidemic activities that help protect
      against metabolic syndrome.

PMID- 30111680
TI  - Superhydrophobic Surfaces on Phase-separated Nanostructures of
      Polystyrene/Polymethyl Methacrylate Films Fabricated by the Double-spray
      Technique.
AB  - Rapid large-area printing techniques are required to fabricate superhydrophobic
      surfaces of polymer films on solid substrates. Here, we report a double-spray
      technique for fabrication of mixed phase-separated films of polystyrene (PS),
      poly(methyl methacrylate) (PMMA), and PS-b-PMMA. The surface wettability of the
      films changes to superhydrophobic by immersing the samples in cyclohexane, which
      is a good solvent for only PS. The rinsing process forms nanostructures in the
      remaining PMMA films that have flat surfaces before the rinsing treatment. The
      highest contact angle is about 150 degrees  on the film with a PMMA ratio of 0.2.
      X-ray photoelectron spectroscopy shows that a small amount of PS remains on the
      surface of the PMMA films, making the films superhydrophobic. Addition of PS-b
      PMMA to the PS/PMMA films forms smaller phase-separated structures than those in
      the original PS/PMMA films because of an increase in the compatibility between PS
      and PMMA. The contact angle hysteresis in the films decreases with increasing PS
      b-PMMA ratio, indicating an increase in the homogeneity of the phase-separated
      structures.

PMID- 30111679
TI  - The Potential of Using Bee Pollen in Cosmetics: a Review.
AB  - During ancient times in China, bee pollen was used for skin whitening and beauty.
      Around 70% of substances in bee pollen are biologically active, such as proteins,
      carbohydrates, lipids and fatty acids, phenolic compounds, vitamins and
      bioelements.This review describes the cosmeceutical properties of bee pollen and
      the mechanism of its active components action, its beneficial influence on human
      skin. As a natural bee product, bee pollen may effectively enhance protective
      mechanisms against skin aging, skin dryness, ultraviolet B radiation, oxidative
      damage, inflammatory and melanogenesis, which are involved in a wide range of
      negative effects on human skin, thus they have attracted attention for health and
      cosmetic applications.

PMID- 30111681
TI  - Novel, Non-aqueous Bioconversion Systems Using Fungal Spores.
AB  - Two novel types of non-aqueous bioconversion systems using fungal spores, either
      adsorbed on the surface of a filter pad or entrapped in calcium alginate beads,
      were constructed and applied for a model reaction: reduction of benzil to benzoin
      by Aspergillus sojae NBRC 32074. The spores adsorbed on a filter pad catalyzed
      the reduction in some toxic organic solvents, such as methylcyclohexane (log P:
      3.61) and din-butyl ether (3.21). For the relationship between the reduction
      activity and the log P value of the organic solvent, a highly positive
      correlation (R2: 0.815) was observed. Surprisingly, the reduction proceeded in
      the more hydrophilic and toxic tert-butyl acetate (log P: 1.76). Glycerol was
      selected as the best hydride source. The higher the glycerol content, the more
      the benzoin was produced. While the production of benzil by spores was lower than
      that by mycelia in harmless di-n-hexyl ether (log P: 5.12), mycelia could not
      catalyze the reduction in the toxic tert-butyl acetate. In contrast, the spores
      entrapped in the calcium alginate beads could catalyze the reduction. Although
      the reduction by alginate-entrapped spores could be stably repeated 5 times in di
      n-hexyl ether without a decline in the reduction activity, it was observed that
      the reduction activity of the spores gradually decreased after repeated reduction
      in tert-butyl acetate.

PMID- 30111682
TI  - Utilization of Lignocellulosic Biomass via Novel Sustainable Process.
AB  - In this review, we show novel methods for utilizing lignocellulosic biomass,
      polysaccharides, and lignin. Firstly, the simultaneous enzymatic saccharification
      and comminution (SESC) of plant materials is described as an extraction method
      for lignocellulosic biomass that does not require toxic reagents or organic
      solvents. Secondly, we demonstrate the material utilization of non-deteriorated
      lignocellulosic biomass extracted by SESC, such as for sugar and ethanol
      synthesis, and as a heatproof filler. Finally, we exhibit the use of a functional
      monomer (e.g., in disinfection chemicals, cesium chelation, and building blocks
      for polymers), 2-pyrone-4,6-dicarboxylic acid, derived from lignin via metabolic
      degradation.

PMID- 30111684
TI  - Macrophage Uptake Behavior and Anti-inflammatory Response of Bovine Brain- or
      Soybean-derived Phosphatidylserine Liposomes.
AB  - Phosphatidylserine (PtdSer) is mainly derived from the bovine brain cortex or
      soybean lecithin. We investigated macrophage uptake behavior and the anti
      inflammatory response induced by liposomes containing bovine brain- (B-PSL) or
      soybean-derived PtdSer (S-PSL). The size of B-PSL and S-PSL was very similar.
      There were no significant differences in the uptake of B-PSL and S-PSL by Raw
      264.7 macrophage cells. Addition of B-PSL or S-PSL decreased the production of
      the inflammatory cytokines, IL-1alpha, IL-6 and TNF-alpha, in lipopolysaccharide
      treated Raw 264.7 cells, but there were no differences between them. These
      results suggest that S-PSL may be used as an anti-inflammatory agent.

PMID- 30111683
TI  - Effect of Oral Paprika Xanthophyll Intake on Abdominal Fat in Healthy Overweight
      Humans: A Randomized, Double-blind, Placebo-controlled Study.
AB  - PURPOSE: Xanthophylls that exist in various vegetables and fruits have beneficial
      actions, such as antioxidant activity and an anti-metabolic syndrome effect, and
      daily intake of xanthophylls could play an important role in preventing lifestyle
      related diseases. We investigated whether intake of xanthophylls from red paprika
      could decrease the abdominal fat area in the healthy overweight volunteers with a
      body mass index (BMI) ranging from 25 to < 30 kg/m2. METHODS: In a randomized,
      double-blind, placebo-controlled, parallel-group study, 100 healthy volunteers
      were assigned to oral administration of paprika xanthophyll capsules (containing
      9.0 mg of paprika xanthophylls) or placebo capsules for 12 weeks. The primary
      endpoint was the effect of paprika xanthophyll intake on the abdominal visceral
      fat area (VFA) as determined by computed tomography. The secondary endpoints were
      as follows: 1) changes of the abdominal subcutaneous fat area (SFA), total fat
      area (TFA), and BMI; 2) changes of lipid metabolism parameters, glucose
      metabolism parameters, and other blood parameters. RESULTS: After 12 weeks, VFA
      was smaller in the paprika xanthophyll group than in the placebo group. In the
      paprika xanthophyll group, there was a significant decrease of SFA, TFA, and BMI
      after 12 weeks compared with baseline, and the reduction of SFA, TFA, and BMI was
      significantly greater in the paprika xanthophyll group than in the placebo group.
      Moreover, total cholesterol and low-density lipoprotein cholesterol decreased
      significantly in the paprika xanthophyll group, but not in the placebo group. No
      adverse effects were caused by intake of paprika xanthophyll capsules.
      CONCLUSIONS: Intake of paprika xanthophylls for 12 weeks significantly reduced
      the abdominal fat area and BMI in healthy overweight volunteers without causing
      any adverse effects. These findings suggest that paprika xanthophyll is a safe
      food ingredient that improves lipid metabolism and reduces abdominal fat. TRIAL
      REGISTRATION: UMIN-CTR UMIN000021529.

PMID- 30111685
TI  - Improvement of Wettability of Photocatalytic TiO2-Coated Wafers by Microwave/UV
      Pre-treatment.
AB  - The wettability efficiency of TiO2-coated Ti substrate wafers was improved using
      a microwave/UV pre-treatment method. With the assistance of microwave heating,
      TiO2 substrates coating with P25 completely achieved super hydrophilic state
      within 5 min, which is twice as fast compared with only UV irradiation condition.
      Moreover, when the microwave power was increased, improvement in the wettability
      activity was observed. Apart from P25, coating with brookite also resulted in a
      good performance. The contact angle was 0 degrees  with only 10 min of
      irradiation.

PMID- 30111686
TI  - Redescription of Subulura (Murisubulura) andersoni (Cobbold, 1876) (Nematoda:
      Subuluridae) from Bunomys spp. (Rodentia: Muridae) of Sulawesi, Indonesia, with
      special reference to S. (M.) suzukii and other related species in the adjacent
      areas.
AB  - Subulura (Murisubulura) andersoni (Cobbold, 1876) (Nematoda: Subuluridae) is
      redescribed in detail using light and scanning electron microscopy based on
      materials collected from Bunomys chrysocomus and Bunomys andrewsi (Rodentia:
      Muridae) of Sulawesi, Indonesia, to provide basic reference data for
      identification. Comparison was made among congeners from adjacent areas,
      especially Subulura (Murisubulura) suzukii Yagi and Kamiya, 1981 of Japan.
      Because morphological differences distinguishing S. (M.) andersoni from S. (M.)
      suzukii and S. (M.) sipiroki were only the thickness of female tail and length of
      male tail, respectively, further study using DNA sequence analysis is necessary
      to prove their distinctness.

PMID- 30111687
TI  - Fat depot-specific differences of macrophage infiltration and cellular senescence
      in obese bovine adipose tissues.
AB  - Obesity is associated with the chronic inflammation and senescence of adipose
      tissues. Macrophage is a key mediator of chronic inflammation that infiltrates
      obese adipose tissue and stimulates metabolic disorders. However, the fat depot
      specific differences of macrophage infiltration and senescence, especially the
      influence on intramuscular adipose tissue, have remained unclear. We investigated
      the fat depot-specific differences of macrophage infiltration and senescence in
      obese bovine adipose tissue from three different anatomical sites (subcutaneous,
      intramuscular and visceral). Macrophage infiltrations and crown-like structures
      were observed in visceral adipose tissue, although there were few macrophages in
      subcutaneous and intramuscular adipose tissues. The positive reaction of
      senescence marker SA-betagal activity was observed in visceral adipose tissue. In
      contrast, the activity of SA-betagal in subcutaneous and intramuscular adipose
      tissues were low. The expression of p53 gene, the master regulator of cellular
      senescence, in visceral adipose tissue was higher than that of subcutaneous and
      intramuscular adipose tissue. At the cellular level, p53 gene expression was
      negatively correlated with the size of subcutaneous adipocytes. In contrast, p53
      gene expressions were positively correlated with the size of intramuscular and
      visceral adipocytes. These results indicate that anatomical sites of obese
      adipose tissue affect macrophage infiltration and the senescent state in a fat
      depot-specific manner.

PMID- 30111688
TI  - Association of Oral Health Literacy and Dental Visitation in an Inner-City
      Emergency Department Population.
AB  - To examine the association between oral health literacy (OHL) with
      sociodemographic variables and dental visitation in adults presenting to an urban
      emergency department (ED). Methods: This was a cross-sectional study of a
      convenience sample of 556 adults aged 18-90. Interview data from the study were
      used to collect self-reported sociodemographic characteristics and dental
      visitation history. The OHL of the study participants was measured using the
      Health Literacy in Dentistry scale (HeLD-14), and the score was dichotomized into
      low and high OHL. Bivariate associations between sociodemographic variables and
      OHL were conducted using chi-square tests, and logistic regression was used to
      examine the association between OHL and dental visitation within the past year.
      Results: Sixty percent of participants reported having visited a dentist within
      the past year. Over two-thirds of the sample was classified as having low OHL.
      Low OHL was more common in non-White races, less-educated, single, unemployed,
      and lower-income individuals, and those without a primary care physician or
      dental insurance (p < 0.05). Patients with low oral health literacy were 39% less
      likely to have visited the dentist in the past year (OR = 0.61; 95% CI 0.38,
      0.96). Conclusions: This study highlights significant disparities in OHL.
      Interventions targeted toward the unique needs of underserved populations should
      be developed to improve health outcomes.

PMID- 30111690
TI  - Improvement in Luminous Efficacy and Thermal Performance Using Quantum Dots
      Spherical Shell for White Light Emitting Diodes.
AB  - White light-emitting diodes (WLEDs) based on quantum dots (QDs) are gaining
      increasing attention due to their excellent color quality. QDs films with planar
      structure are universally applied in WLEDs for color conversion, while they still
      face great challenges in high light extraction and thermal stability. In this
      study, a QDs film with a spherical shell structure was proposed to improve the
      optical and thermal performance for WLEDs. Compared with the conventional planar
      structure, the luminous efficacy of the QDs spherical shell structure is improved
      by 12.9% due to the reduced total reflection effect, and the angular-dependent
      correlated color temperature deviation is decreased from 2642 to 283 K. Moreover,
      the highest temperature of the WLED using a QDs spherical shell is 4.8  degrees C
      lower than that of the conventional WLED with a planar structure, which is mainly
      attributed to larger heat dissipation area and separated heat source.
      Consequently, this QDs spherical shell structure demonstrates superior
      performance of QDs films for WLEDs applications.

PMID- 30111689
TI  - NOX Inhibition Improves beta-Adrenergic Stimulated Contractility and
      Intracellular Calcium Handling in the Aged Rat Heart.
AB  - Cardiac aging is characterized by alterations in contractility and intracellular
      calcium ([Ca2+]i) homeostasis. It has been suggested that oxidative stress may be
      involved in this process. We and others have reported that in cardiomyopathies
      the NADPH oxidase (NOX)-derived superoxide is increased, with a negative impact
      on [Ca2+]i and contractility. We tested the hypothesis that in the aged heart,
      [Ca2+]i handling and contractility are disturbed by NOX-derived superoxide. For
      this we used adults (~5 month-old) and aged (20-24 month-old) rats. Contractility
      was evaluated in isolated hearts, challenged with isoproterenol. To assess
      [Ca2+]i, isolated cardiac myocytes were field-stimulated and [Ca2+]i was
      monitored with fura-2. Cardiac concentration-response to isoproterenol was
      depressed in aged compared to adults hearts (p < 0.005), but was restored by NOX
      inhibitors apocynin and VAS2870. In isolated cardiomyocytes, apocynin increased
      the amplitude of [Ca2+]i in aged myocytes (p < 0.05). Time-50 [Ca2+]i decay was
      increased in aged myocytes (p < 0.05) and reduced towards normal by NOX
      inhibition. In addition, we found that myofilaments Ca2+ sensitivity was reduced
      in aged myocytes (p < 0.05), and was further reduced by apocynin. NOX2 expression
      along with NADPH oxidase activity was increased in aged hearts. Phospholamban
      phosphorylation (Ser16/Thr17) after isoproterenol treatment was reduced in aged
      hearts compared to adults and was restored by apocynin treatment (p < 0.05). In
      conclusion, beta-adrenergic-induced contractility was depressed in aged hearts,
      and NOX inhibition restored back to normal. Moreover, altered Ca2+ handling in
      aged myocytes was also improved by NOX inhibition. These results suggest a NOX
      dependent effect in aged myocytes at the level of Ca2+ handling proteins and
      myofilaments.

PMID- 30111692
TI  - Analysis of Force Signals for the Estimation of Surface Roughness during Robot
      Assisted Polishing.
AB  - In this study feature extraction of force signals detected during robot-assisted
      polishing processes was carried out to estimate the surface roughness during the
      process. The purpose was to collect significant features from the signal that
      allow the determination of the end point of the polishing process based on
      surface roughness. For this objective, dry polishing turning tests were performed
      on a Robot-Assisted Polishing (RAP) machine (STRECON NanoRAP 200) during three
      polishing sessions, using the same polishing conditions. Along the tests, force
      signals were acquired and offline surface roughness measurements were taken at
      the end of each polishing session. As a main conclusion, it can be affirmed,
      regarding the force signal, that features extracted from both time and frequency
      domains are valuable data for the estimation of surface roughness.

PMID- 30111693
TI  - Translating Research as an Approach to Enhance Science Engagement.
AB  - The impact of research depends on the effective communication of discoveries.
      Scientific writing is the primary tool for the dissemination of research, and is
      an important skill that biomedical trainees have to develop. Despite its
      importance, scientific writing is not part of the mainstream curriculum. One
      strategy used to teach scientific writing is holding a journal club style
      discussion of primary research literature that the students are asked to read.
      However, this activity can result in a passive learning experience and limit the
      development of trainees' scientific writing skills. In order to improve trainees'
      written communication skills, we tested an exercise that involved generating a
      revised article describing prior research, in essence "translating" the science
      into basic language. Following the guidelines set out by "Frontiers for Young
      Minds" and feedback received from "Young Reviewers", we wrote a revised article
      with a simpler description of the research. In this article, we describe this
      scientific writing exercise, which may ultimately serve as a model for scientists
      to share their research more efficiently in order to promote better public health
      outcomes.

PMID- 30111691
TI  - Edema Induced by a Crotalus durissus terrificus Venom Serine Protease (Cdtsp 2)
      Involves the PAR Pathway and PKC and PLC Activation.
AB  - Snake venom serine proteases (SVSPs) represent an essential group of enzymatic
      toxins involved in several pathophysiological effects on blood homeostasis. Some
      findings suggest the involvement of this class of enzymatic toxins in
      inflammation. In this paper, we purified and isolated a new gyroxin isoform from
      the Crotalus durissus terrificus (Cdt) venom, designated as Cdtsp 2, which showed
      significant proinflammatory effects in a murine model. In addition, we performed
      several studies to elucidate the main pathway underlying the edematogenic effect
      induced by Cdtsp 2. Enzymatic assays and structural analysis (primary structure
      analysis and three-dimensional modeling) were closely performed with
      pharmacological assays. The determination of edematogenic activity was performed
      using Cdtsp 2 isolated from snake venom, and was applied to mice treated with
      protein kinase C (PKC) inhibitor, phospholipase C (PLC) inhibitor, dexamethasone
      (Dexa), antagonists for protease-activated receptors (PARs), or saline (negative
      control). Additionally, we measured the levels of cyclooxygenase 2 (COX-2),
      malondialdehyde (MDA), and prostaglandin E2 (PGE2). Cdtsp 2 is characterized by
      an approximate molecular mass of 27 kDa, an isoelectric point (pI) of 4.5, and
      significant fibrinolytic activity, as well as the ability to hydrolyze Nalpha
      benzoyl-l-arginine 4-nitroanilide (BAPNA). Its primary and three-dimensional
      structures revealed Cdtsp 2 as a typical snake venom serine protease that induces
      significant edema via the metabolism of arachidonic acid (AA), involving PARs,
      PKC, PLC, and COX-2 receptors, as well as inducing a significant increase in MDA
      levels. Our results showed that Cdtsp 2 is a serine protease with significant
      enzymatic activity, and it may be involved in the degradation of PAR1 and PAR2,
      which activate PLC and PKC to mobilize AA, while increasing oxidative stress. In
      this article, we provide a new perspective for the role of SVSPs beyond their
      effects on blood homeostasis.

PMID- 30111694
TI  - Understanding the Needs of Veterans with PTSD.

PMID- 30111696
TI  - Immobilization of Graphene Oxide on the Permeate Side of a Membrane Distillation
      Membrane to Enhance Flux.
AB  - In this paper, a facile fabrication of enhanced direct contact membrane
      distillation membrane via immobilization of the hydrophilic graphene oxide (GO)
      on the permeate side (GOIM-P) of a commercial polypropylene supported
      polytetrafluoroethylene (PTFE) membrane is presented. The permeate side
      hydrophilicity of the membrane was modified by immobilizing the GO to facilitate
      fast condensation and the withdrawal of the permeate water vapors. The water
      vapor flux was found to be as high as 64.5 kg/m2.h at 80  degrees C, which is 15%
      higher than the unmodified membrane at a feed salt concentration of 10,000 ppm.
      The mass transfer coefficient was observed 6.2 * 10-7 kg/m2.s.Pa at 60  degrees C
      and 200 mL/min flow rate in the GOIM-P.

PMID- 30111695
TI  - Cinnamoyl-Oxaborole Amides: Synthesis and Their in Vitro Biological Activity.
AB  - Due to the increased interest in their application in the treatment of infectious
      diseases, boron-containing compounds have received a significant coverage in the
      literature. Herein, a small set of novel cinnamoly-oxaborole amides were
      synthesized and screened against nagana Trypanosoma brucei brucei for
      antitrypanosomal activity. Compound 5g emerged as a new hit with an in vitro IC50
      value of 0.086 MUM against T. b. brucei without obvious inhibitory activity
      against HeLa cell lines. The same series was also screened against other human
      pathogens, including Mycobacterium tuberculosis, the causative agent of
      tuberculosis (TB), for which moderate to weak activity (10 to >125 MUM) was
      observed. Similarly, these compounds exhibited moderate activity against the
      human protozoal pathogen Trichomonas vaginalis with no observed effect on common
      microbiome bacterial species. The cross-species inhibitory activity presents the
      possibility of these compounds serving as broad-spectrum antibiotics for these
      prevalent three human pathogens.

PMID- 30111697
TI  - A Method for 6D Pose Estimation of Free-Form Rigid Objects Using Point Pair
      Features on Range Data.
AB  - Pose estimation of free-form objects is a crucial task towards flexible and
      reliable highly complex autonomous systems. Recently, methods based on range and
      RGB-D data have shown promising results with relatively high recognition rates
      and fast running times. On this line, this paper presents a feature-based method
      for 6D pose estimation of rigid objects based on the Point Pair Features voting
      approach. The presented solution combines a novel preprocessing step, which takes
      into consideration the discriminative value of surface information, with an
      improved matching method for Point Pair Features. In addition, an improved
      clustering step and a novel view-dependent re-scoring process are proposed
      alongside two scene consistency verification steps. The proposed method
      performance is evaluated against 15 state-of-the-art solutions on a set of
      extensive and variate publicly available datasets with real-world scenarios under
      clutter and occlusion. The presented results show that the proposed method
      outperforms all tested state-of-the-art methods for all datasets with an overall
      6.6% relative improvement compared to the second best method.

PMID- 30111699
TI  - Highly Sensitive and Selective Colorimetric Detection of Methylmercury Based on
      DNA Functionalized Gold Nanoparticles.
AB  - A new colorimetric detection of methylmercury (CH3Hg+) was developed, which was
      based on the surface deposition of Hg enhancing the catalytic activity of gold
      nanoparticles (AuNPs). The AuNPs were functionalized with a specific DNA strand
      (HT7) recognizing CH3Hg+, which was used to capture and separate CH3Hg+ by
      centrifugation. It was found that the CH3Hg+ reduction resulted in the deposition
      of Hg onto the surface of AuNPs. As a result, the catalytic activity of the AuNPs
      toward the chromogenic reaction of 3,3,5,5-tetramethylbenzidine (TMB)-H2O2 was
      remarkably enhanced. Under optimal conditions, a limit of detection of 5.0 nM was
      obtained for CH3Hg+ with a linear range of 10-200 nM. We demonstrated that the
      colorimetric method was fairly simple with a low cost and can be conveniently
      applied to CH3Hg+ detection in environmental samples.

PMID- 30111698
TI  - Adverse Effects of Fenofibrate in Mice Deficient in the Protein Quality Control
      Regulator, CHIP.
AB  - We previously reported how the loss of CHIP expression (Carboxyl terminus of
      Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac
      dysfunction, which was accompanied by a failure to maintain ATP levels in the
      face of increased energy demand. In this study, we analyzed the cardiac
      metabolome after seven days of pressure overload and found an increase in long
      chain and medium-chain fatty acid metabolites in wild-type hearts. This response
      was attenuated in mice that lack expression of CHIP (CHIP-/-). These findings
      suggest that CHIP may play an essential role in regulating oxidative metabolism
      pathways that are regulated, in part, by the nuclear receptor PPARalpha
      (Peroxisome Proliferator-Activated Receptor alpha). Next, we challenged CHIP-/-
      mice with the PPARalpha agonist called fenofibrate. We found that treating CHIP-/
      mice with fenofibrate for five weeks under non-pressure overload conditions
      resulted in decreased skeletal muscle mass, compared to wild-type mice, and a
      marked increase in cardiac fibrosis accompanied by a decrease in cardiac
      function. Fenofibrate resulted in decreased mitochondrial cristae density in CHIP
      /- hearts as well as decreased expression of genes involved in the initiation of
      autophagy and mitophagy, which suggests that a metabolic challenge, in the
      absence of CHIP expression, impacts pathways that contribute to mitochondrial
      quality control. In conclusion, in the absence of functional CHIP expression,
      fenofibrate results in unexpected skeletal muscle and cardiac pathologies. These
      findings are particularly relevant to patients harboring loss-of-function
      mutations in CHIP and are consistent with a prominent role for CHIP in regulating
      cardiac metabolism.

PMID- 30111700
TI  - Heat-Resistant Ferroelectric-Polymer Nanocomposite with High Dielectric Constant.
AB  - The high dielectric constant ferroelectric-polymer nanocomposite was developed
      for producing the heat-resistant and chemical stable planar layers. According to
      the composite coatings formation conditions, the following value ranges of
      dielectric constant and loss factor were received: 30-400 for dielectric constant
      and 0.04-0.1 for loss tangent, accordingly. Unlike of composite components, the
      obtained composite material is characterized by thermo-stability of electrical
      parameters up to 250  degrees C. The dielectric frequency spectra of the
      composite exhibit two clearly visible peaks in contrast to the spectra of the
      polymer and ferroelectric ceramics. The developed composite material can be used
      as a built-in film capacitors material in microelectronic devices.

PMID- 30111701
TI  - Improved Methods for the Rapid Formation and Prevention of Advanced Glycation End
      Products (AGEs) In Vitro by Coupling to the Hypoxanthine/Xanthine Oxidase Assay
      System.
AB  - Advanced glycation end products (AGEs) represent a set of molecules that
      contribute directly to the initiation and aggravation of diseases associated with
      ageing. AGEs are produced by the reaction between reducing sugars (or alpha
      dicarbonyl compounds), proteins, and amino acid residues. Previous in vitro
      methods using non-enzymatic procedures described in the literature require an
      incubation period of 1-3 weeks to generate AGEs. In this study, the reaction time
      for the formation of AGEs (48 and 3 h) was significantly reduced by adaptation of
      methods previously described in the literature and coupling them to the free
      radical generation system termed hypoxanthine/xanthine oxidase assay. The
      incorporation of this assay into the experimental system accelerated the
      production of AGEs as a result of the formation of reactive oxygen species (ROS),
      as shown by increased fluorescence. The capacity of different classes of chemical
      compounds (aminoguanidine, chlorogenic acid, rutin, and methanol extracts of
      Hancornia speciosa Gomes) to inhibit protein glycation by acting as scavenging
      agents of alpha-dicarbonyl species was evaluated. Aminoguanidine and, especially,
      rutin identified in the leaf extracts of H. speciosa Gomes showed a high capacity
      to act as scavengers of reactive carbonyl species RCS-trapping, resulting in the
      inhibition of AGEs formation.

PMID- 30111702
TI  - Oviplate: A Convenient and Space-Saving Method to Perform Individual Oviposition
      Assays in Aedes aegypti.
AB  - Aedes aegypti is the principal vector of the urban arboviruses and the blood
      ingestion is important to produce the eggs in this species. To analyze the egg
      production in Ae. aegypti, researchers frequently use small cages or Drosophila
      vials to collect eggs from gravid females. Although it is affordable, the setup
      is time- and space-consuming, mainly when many mosquitoes need to be individually
      analyzed. This study presents an easy, cheap, and space-saving method to perform
      individual oviposition assays in Ae. aegypti using cell culture plates. This new
      method to access fecundity rate was named "oviplate". The oviplates are setup
      with 12- or 24-well plates, distilled water and filter paper and they are 78 to
      88% cheaper than the traditional Drosophila vial assay, respectively.
      Furthermore, to allocate 72 vitellogenic females in an insectary using Drosophila
      vial is necessary 4100 cm3 against 1400 cm3 and 700 cm3 when using 12- and 24
      well plates, respectively. No statistical differences were found between the
      number of eggs laid in Drosophila vials and the oviplates, validating the method.
      The oviplate method is an affordable, and time- and space-efficient device, and
      it is simpler to perform individual fecundity analyses in Ae. aegypti.

PMID- 30111703
TI  - Effects of Oat Bran on Nutrient Digestibility, Intestinal Microbiota, and
      Inflammatory Responses in the Hindgut of Growing Pigs.
AB  - Oat bran has drawn great attention within human research for its potential role
      in improving gut health. However, research regarding the impact of oat bran on
      nutrient utilization and intestinal functions in pigs is limited. The purpose of
      this study was to investigate the effects of oat bran on nutrient digestibility,
      intestinal microbiota, and inflammatory responses in the hindgut of growing pigs.
      Twenty-six growing pigs were fed either a basal diet (CON) or a basal diet
      supplemented with 10% oat bran (OB) within a 28 day feeding trial. Results showed
      that digestibility of dietary gross energy, dry matter, organic matter, and crude
      protein were lower in the OB group compared to the CON group on day 14, but no
      differences were observed between the two groups on day 28. In the colon, the
      relative abundance of operational taxonomic units (OTUs) associated with
      Prevotella, Butyricicoccus, and Catenibacterium were higher, while those
      associated with Coprococcus and Desulfovibrio were lower in the OB group compared
      to the CON group. Oat bran decreased mRNA expression of caecal interleukin-8 (IL
      8), as well as colonic IL-8, nuclear factor-kappaB (NF-kappaB), and tumor
      necrosis factor-alpha (TNF-alpha) of the pigs. In summary, oat bran treatment for
      28 day did not affect dietary nutrient digestibility, but promoted the growth of
      cellulolytic bacteria and ameliorated inflammatory reactions in the hindgut of
      growing pigs.

PMID- 30111704
TI  - Enhancement of Electrical Characteristics and Stability of Amorphous Si-Sn-O Thin
      Film Transistors with SiOx Passivation Layer.
AB  - In this research, a passivated methodology was proposed for achieving good
      electrical characteristics for back-channel-etch (BCE) typed amorphous Si-Sn-O
      thin film transistors (a-STO TFTs). This methodology implied that the thermal
      annealing (i.e., pre-annealing) should be carried out before deposition of a SiOx
      passivation layer. The pre-annealing played an important role in affecting device
      performance, which did get rid of the contamination of the lithography process.
      Simultaneously, the acceptor-like sub-gap density of states (DOS) of devices was
      extracted for further understanding the reason for improving device performance.
      It found that the SiOx layer could reduce DOS of the device and successfully
      protect the device from surroundings. Finally, a-STO TFT applied with this
      passivated methodology could possess good electrical properties including a
      saturation mobility of 4.2 +/- 0.2 cm2/V s, a low threshold voltage of 0.00 V, a
      large on/off current ratio of 6.94 * 108, and a steep subthreshold swing of 0.23
      V/decade. The threshold voltage slightly shifted under bias stresses and
      recovered itself to its initial state without any annealing procedure, which was
      attributed to the charge trapping in the bulk dielectric layers or interface. The
      results of this study indicate that a-STO TFT could be a robust candidate for
      realizing a large-size and high-resolution display.

PMID- 30111705
TI  - Bacteriophage Sf6 Tailspike Protein for Detection of Shigella flexneri Pathogens.
AB  - Bacteriophage research is gaining more importance due to increasing antibiotic
      resistance. However, for treatment with bacteriophages, diagnostics have to be
      improved. Bacteriophages carry adhesion proteins, which bind to the bacterial
      cell surface, for example tailspike proteins (TSP) for specific recognition of
      bacterial O-antigen polysaccharide. TSP are highly stable proteins and thus might
      be suitable components for the integration into diagnostic tools. We used the TSP
      of bacteriophage Sf6 to establish two applications for detecting Shigella
      flexneri (S. flexneri), a highly contagious pathogen causing dysentery. We found
      that Sf6TSP not only bound O-antigen of S. flexneri serotype Y, but also the
      glucosylated O-antigen of serotype 2a. Moreover, mass spectrometry glycan
      analyses showed that Sf6TSP tolerated various O-acetyl modifications on these O
      antigens. We established a microtiter plate-based ELISA like tailspike adsorption
      assay (ELITA) using a Strep-tag(r)II modified Sf6TSP. As sensitive screening
      alternative we produced a fluorescently labeled Sf6TSP via coupling to an
      environment sensitive dye. Binding of this probe to the S. flexneri O-antigen Y
      elicited a fluorescence intensity increase of 80% with an emission maximum in the
      visible light range. The Sf6TSP probes thus offer a promising route to a highly
      specific and sensitive bacteriophage TSP-based Shigella detection system.

PMID- 30111708
TI  - Technetium Complexes and Radiopharmaceuticals with Scorpionate Ligands.
AB  - Scorpionate ligands have played a crucial role in the development of technetium
      chemistry and, recently, they have also fueled important advancements in the
      discovery of novel diagnostic imaging agents based on the gamma-emitting
      radionuclide technetium-99m. The purpose of this short review is to provide an
      illustration of the most general and relevant results in this field, however
      without being concerned with the details of the analytical features of the
      various compounds. Thus, emphasis will be given to the description of the general
      features of technetium complexes with scorpionate ligands including coordination
      modes, structural properties and an elementary bonding description. Similarly,
      the most relevant examples of technetium-99m radiopharmaceuticals derived from
      scorpionate ligands and their potential interest for nuclear imaging will be
      summarized.

PMID- 30111710
TI  - Wave2Vec: Vectorizing Electroencephalography Bio-Signal for Prediction of Brain
      Disease.
AB  - Interest in research involving health-medical information analysis based on
      artificial intelligence, especially for deep learning techniques, has recently
      been increasing. Most of the research in this field has been focused on searching
      for new knowledge for predicting and diagnosing disease by revealing the relation
      between disease and various information features of data. These features are
      extracted by analyzing various clinical pathology data, such as EHR (electronic
      health records), and academic literature using the techniques of data analysis,
      natural language processing, etc. However, still needed are more research and
      interest in applying the latest advanced artificial intelligence-based data
      analysis technique to bio-signal data, which are continuous physiological
      records, such as EEG (electroencephalography) and ECG (electrocardiogram). Unlike
      the other types of data, applying deep learning to bio-signal data, which is in
      the form of time series of real numbers, has many issues that need to be resolved
      in preprocessing, learning, and analysis. Such issues include leaving feature
      selection, learning parts that are black boxes, difficulties in recognizing and
      identifying effective features, high computational complexities, etc. In this
      paper, to solve these issues, we provide an encoding-based Wave2vec time series
      classifier model, which combines signal-processing and deep learning-based
      natural language processing techniques. To demonstrate its advantages, we provide
      the results of three experiments conducted with EEG data of the University of
      California Irvine, which are a real-world benchmark bio-signal dataset. After
      converting the bio-signals (in the form of waves), which are a real number time
      series, into a sequence of symbols or a sequence of wavelet patterns that are
      converted into symbols, through encoding, the proposed model vectorizes the
      symbols by learning the sequence using deep learning-based natural language
      processing. The models of each class can be constructed through learning from the
      vectorized wavelet patterns and training data. The implemented models can be used
      for prediction and diagnosis of diseases by classifying the new data. The
      proposed method enhanced data readability and intuition of feature selection and
      learning processes by converting the time series of real number data into
      sequences of symbols. In addition, it facilitates intuitive and easy recognition,
      and identification of influential patterns. Furthermore, real-time large-capacity
      data analysis is facilitated, which is essential in the development of real-time
      analysis diagnosis systems, by drastically reducing the complexity of calculation
      without deterioration of analysis performance by data simplification through the
      encoding process.

PMID- 30111709
TI  - Structure and Bioactivity Screening of a Low Molecular Weight Ulvan from the
      Green Alga Ulothrix flacca.
AB  - A water-soluble low molecular-weight polysaccharide named UP2-1 was isolated and
      purified from the marine green algae Ulothrixflacca using ion-exchange and size
      exclusion chromatography. Composition and characteristics analyses showed that
      UP2-1 was a sulfated glucuronorhamnan consisting of rhamnose and glucuronic acid
      in a ratio of 2:1 with 21% sulfate content and a molecular weight of 5.0 kDa.
      Structural properties were determined using desulfation and methylation analyses
      combined with infrared spectrum (IR), gas chromatography-mass spectrometer (GC
      MS) and nuclear magnetic resonance (NMR). The results showed that UP2-1 was a
      type of ulvan composed of alternate 4-linked-alpha-L-rhamnose residues (->4)
      alpha-L-Rha(1->) and 4-linked-beta-D-glucouronoc acid residues. The sulfate
      groups were mainly present in the O-3 position of ->4)-alpha-L-Rha(1->. Most
      (70%) of the rhamnose was sulfated. UP2-1 also had a small amount of ->4)-alpha-L
      Rha(1-> branch at the O-2 position of the ->4)-alpha-L-Rha(1->. UP2-1 exhibited
      significant anticoagulant and immunomodulating activity in vitro. This study
      demonstrated that the green algae Ulothrix flacca, which is used as a food and
      traditional marine herb in China, could also be considered as a source of
      bioactive ulvan.

PMID- 30111706
TI  - Messing with the Sentinels-The Interaction of Staphylococcus aureus with
      Dendritic Cells.
AB  - Staphylococcus aureus (S. aureus) is a dangerous pathogen as well as a frequent
      colonizer, threatening human health worldwide. Protection against S. aureus
      infection is challenging, as the bacteria have sophisticated strategies to escape
      the host immune response. To maintain equilibrium with S. aureus, both innate and
      adaptive immune effector mechanisms are required. Dendritic cells (DCs) are
      critical players at the interface between the two arms of the immune system,
      indispensable for inducing specific T cell responses. In this review, we
      highlight the importance of DCs in mounting innate as well as adaptive immune
      responses against S. aureus with emphasis on their role in S. aureus-induced
      respiratory diseases. We also review what is known about mechanisms that S.
      aureus has adopted to evade DCs or manipulate these cells to its advantage.

PMID- 30111707
TI  - Responses of Transgenic Melatonin-Enriched Goats on LPS Stimulation and the
      Proteogenomic Profiles of Their PBMCs.
AB  - The anti-inflammatory activity of melatonin (MT) has been well documented;
      however, little is known regarding endogenously occurring MT in this respect,
      especially for large animals. In the current study, we created a MT-enriched
      animal model (goats) overexpressing the MT synthetase gene Aanat. The responses
      of these animals to lipopolysaccharide (LPS) stimulation were systematically
      studied. It was found that LPS treatment exacerbated the inflammatory response in
      wild-type (WT) goats and increased their temperature to 40  degrees C. In
      addition, their granulocyte counts were also significantly elevated. In contrast,
      these symptoms were not observed in transgenic goats with LPS treatment. The
      rescue study with MT injection into WT goats who were treated with LPS confirmed
      that the protective effects in transgenic goats against LPS were attributed to a
      high level of endogenously produced MT. The proteomic analysis in the peripheral
      blood mononuclear cells (PBMCs) isolated from the transgenic animals uncovered
      several potential mechanisms. MT suppressed the lysosome formation as well as its
      function by downregulation of the lysosome-associated genes Lysosome-associated
      membrane protein 2 (LAMP2), Insulin-like growth factor 2 receptor (IGF2R), and
      Arylsulfatase B (ARSB). A high level of MT enhanced the antioxidant capacity of
      these cells to reduce the cell apoptosis induced by the LPS. In addition, the
      results also uncovered previously unknown information that showed that MT may
      have protective effects on some human diseases, including tuberculosis, bladder
      cancer, and rheumatoid arthritis, by downregulation of these disease-associated
      genes. All these observations warranted further investigations.

PMID- 30111711
TI  - Nasal Planum Vasculopathy in a Scottish Terrier Dog Treated with Ciclosporin and
      Endonasal Stents.
AB  - A two-year-old, intact female Scottish Terrier presented with one-and-a-half-year
      history of erosive and ulcerative lesions affecting the nasal planum. Clinical
      appearance, history, histopathology, and response to therapy were suggestive of a
      rare vasculopathy of the nasal planum that has been previously described in
      Scottish Terrier dogs. In previously published reports, medical treatments of the
      disease had failed, leading to euthanasia of five dogs, while a short-term follow
      up was available for one case that was controlled with prednisolone and
      ciclosporin. The dog reported herein was successfully treated with medical
      therapy consisting initially of a combination of ciclosporin and prednisolone and
      endonasal stents applied over the first six months. Stents were inserted in order
      to prevent abnormal scarring and nostril stenosis. More than one and a half years
      after diagnosis, the dog is still being administered ciclosporin once daily,
      breathes normally, and has an optimal quality of life.

PMID- 30111712
TI  - Physical and Mental Health Impacts of Household Gardens in an Urban Slum in Lima,
      Peru.
AB  - Rural poverty and lack of access to education has led to urban migration and fed
      the constant growth of urban slums in Lima, Peru. Inhabitants of these informal
      settlements lack land rights and access to a public water supply, resulting in
      poor sanitation, an inability to grow food, and suboptimal health outcomes. A
      repeated measures longitudinal pilot study utilizing participatory design methods
      was conducted in Lima between September 2013 and September 2014 to determine the
      feasibility of implementing household gardens and the subsequent impact of
      increased green space on well-being. Anthropometric data and a composite of five
      validated mental health surveys were collected at the baseline, 6-months, and 12
      months after garden construction. Significant increases from the baseline in all
      domains of quality of life, including: physical (p < 0.01), psychological (p =
      0.05), social (p = 0.02), environmental (p = 0.02), and overall social capital (p
      < 0.01) were identified 12 months after garden construction. Life-threatening
      experiences decreased significantly compared to the baseline (p = 0.02). There
      were no significant changes in parent or partner empathy (p = 0.21), BMI (p =
      0.95), waist circumference (p = 0.18), or blood pressure (p = 0.66) at 6 or 12
      months. Improved access to green space in the form of a household garden can
      significantly improve mental health in an urban slum setting.

PMID- 30111713
TI  - Generalized Optical Design of the Double-Row Circular Multi-Pass Cell.
AB  - A new design of circular multi-pass cells (CMPC) with two rows of reflection
      spots on mirrors is presented. The effective optical path length (OPL) of this
      novel CMPC is double that of traditional CMPC with the same diameter and interval
      of spots. This OPL can be readily adjusted to have regular intervals by rough
      rotation adjustment. We achieved a spatial separation of pre- and post-transfer
      optical systems that was adequately large even in the cases with a large number
      of passes. Analytical chief ray tracing analysis and a generalized method for
      parameter determination for designing the cell are presented in detail. The
      stable condition of the double-row CMPC (DR-CMPC) is also derived by the ABCD
      matrix method. Designs with maximum effective OPL of 74.72 m, 48.67 m and 24.57 m
      are demonstrated and verified by ray tracing simulations within a 25 cm diameter
      DR-CMPC. An adjustment of the regular intervals to 1 m can be achieved in both
      designs. The overall astigmatism of the design with an effective OPL of 74.72 m
      is only 9.30 * 10-6 mm, which is four orders of magnitude smaller than that of
      the traditional CMPC with similar geometric parameters.

PMID- 30111715
TI  - Reliability of and Relationship between Flight Time to Contraction Time Ratio and
      Reactive Strength Index Modified.
AB  - Countermovement jump (CMJ) force-time testing is commonly used to monitor
      seasonal alterations in athletes' CMJ strategy (to infer alterations in
      neuromuscular function). The flight time to contraction time (FT:CT) ratio and
      reactive strength index modified (RSImod) are considered to be two primary CMJ
      variables of interest. Due to similar calculations, it is likely that the FT:CT
      ratio and RSImod share similar reliability and an almost perfect relationship.
      Consequently, there may be no requirement to include both variables in CMJ
      monitoring reports. This study aimed to investigate this by recruiting twenty
      five males to perform three CMJs on a force platform across two sessions that
      were separated by one week. The FT:CT ratio and two calculations of RSImod (based
      on the jump height from either flight time or take-off velocity) were then
      calculated using robust methods. The between-day reliability was good-excellent
      for all of the variables (95% confidence interval range of the coefficient of
      variation = 2.02-9.22%) with no significant between-day differences noted (p >=
      0.231). There was an almost perfect positive relationship between the FT:CT ratio
      and RSImod regardless of the calculation method (r = 0.944-0.947, p < 0.001). As
      the FT:CT ratio and RSImod yield similar absolute reliability and share 90% of
      common variance, there is little reason to include both variables in CMJ
      monitoring reports.

PMID- 30111716
TI  - Atmospheric Pressure Plasma-Mediated Synthesis of Platinum Nanoparticles
      Stabilized by Poly(vinylpyrrolidone) with Application in Heat Management Systems
      for Internal Combustion Chambers.
AB  - Poly(vinylpyrrolidone)-stabilized Pt nanoparticles (PVP-PtNPs) were produced in a
      continuous-flow reaction-discharge system by application of direct current
      atmospheric pressure glow discharge (dc-APGD) operated between the surface of a
      flowing liquid anode (FLA) and a pin-type tungsten cathode. Synthesized PVP-PtNPs
      exhibited absorption across the entire UV/Vis region. The morphology and
      elemental composition of PVP-PtNPs were determined with transmission electron
      microscopy (TEM) and energy dispersive X-ray scattering (EDX), respectively. As
      assessed by TEM, PVP-PtNPs were approximately spherical in shape, with an average
      size of 2.9 +/- 0.6 nm. EDX proved the presence of Pt, C, and O. Dynamic light
      scattering (DLS) and attenuated total reflectance Fourier transform-infrared
      spectroscopy (ATR FT-IR) confirmed PtNPs functionalization with PVP. As
      determined by DLS, the average size of PtNPs stabilized by PVP was 111.4 +/- 22.6
      nm. A fluid containing resultant PVP-PtNPs was used as a heat conductive layer
      for a spiral radiator managing heat generated by a simulated internal combustion
      chamber. As compared to water, the use of PVP-PtNPs enhanced efficiency of the
      system, increasing the rate of heat transfer by 80% and 30% during heating and
      cooling, respectively.

PMID- 30111714
TI  - Tau in Oligodendrocytes Takes Neurons in Sickness and in Health.
AB  - Oligodendrocytes (OLGs), the myelin-forming cells of the central nervous system
      (CNS), are lifelong partners of neurons. They adjust to the functional demands of
      neurons over the course of a lifetime to meet the functional needs of a healthy
      CNS. When this functional interplay breaks down, CNS degeneration follows. OLG
      processes are essential features for OLGs being able to connect with the neurons.
      As many as fifty cellular processes from a single OLG reach and wrap an equal
      number of axonal segments. The cellular processes extend to meet and wrap axonal
      segments with myelin. Further, transport regulation, which is critical for
      myelination, takes place within the cellular processes. Because the microtubule
      associated protein tau plays a crucial role in cellular process extension and
      myelination, alterations of tau in OLGs have deleterious effects, resulting in
      neuronal malfunction and CNS degeneration. Here, we review current concepts on
      the lifelong role of OLGs and myelin for brain health and plasticity. We present
      key studies of tau in OLGs and select important studies of tau in neurons. The
      extensive work on tau in neurons has considerably advanced our understanding of
      how tau promotes either health or disease. Because OLGs are crucial to neuronal
      health at any age, an understanding of the functions and regulation of tau in
      OLGs could uncover new therapeutics for selective CNS neurodegenerative diseases.

PMID- 30111718
TI  - A Comparative Study of Three Types Shear Mode Piezoelectric Wafers in Shear
      Horizontal Wave Generation and Reception.
AB  - Guided wave-based inspection has emerged as a promising tool to evaluate the
      reliability of key components in modern industries. The fundamental shear
      horizontal (SH0) wave is always of great interests for plate-like structures
      because of its non-dispersion characteristics. However, the generation and
      reception of SH0 wave using piezoelectric wafers is not straightforward. In this
      paper, we firstly define three types shear mode piezoelectric wafers, i.e., the
      conventional in-plane poled thickness-shear (d15) mode, the thickness-poled
      thickness-shear (d15) mode, and the face-shear (d24) mode. Then, finite element
      simulations were conducted to demonstrate their performance in SH wave generation
      and reception. The results indicated that the face shear d24 wafer can generate
      almost single mode SH0 wave, while both types of d15 wafers would generate Lamb
      waves and SH0 wave simultaneously. Finally, experiments were carried out to check
      the efficiency of different shear mode piezoelectric wafers in SH0 wave
      generation and reception. The results indicated that the d24 wafer can generate
      and receive SH0 wave of high signal to noise ratio (SNR) with high energy
      conversion efficiency, while the in-plane poled d15 wafer would generate SH0 wave
      of high amplitude and acceptable SNR but with relatively low energy conversion
      efficiency. The performances of thickness-poled d15 wafer was not as good as the
      other two in both SH wave generation and reception. This work will be helpful for
      the applications of SH waves in plate-like structures.

PMID- 30111717
TI  - A Dynamic Overview of Antimicrobial Peptides and Their Complexes.
AB  - In this narrative review, we comprehensively review the available information
      about the recognition, structure, and dynamics of antimicrobial peptides (AMPs).
      Their complex behaviors occur across a wide range of time scales and have been
      challenging to portray. Recent advances in nuclear magnetic resonance and
      molecular dynamics simulations have revealed the importance of the molecular
      plasticity of AMPs and their abilities to recognize targets. We also highlight
      experimental data obtained using nuclear magnetic resonance methodologies,
      showing that conformational selection is a major mechanism of target interaction
      in AMP families.

PMID- 30111720
TI  - Exploration of the Association between Dietary Fiber Intake and Hypertension
      among U.S. Adults Using 2017 American College of Cardiology/American Heart
      Association Blood Pressure Guidelines: NHANES 2007-2014.
AB  - This study aimed to explore the association between dietary fiber intake and
      hypertension risk using 2017 American College of Cardiology/American Heart
      Association Blood Pressure Guidelines. Data from the National Health and
      Nutrition Examination Survey 2007-2014 were used in this study. Dietary fiber
      data were obtained through two 24-h dietary recall interviews. Hypertension was
      defined as systolic blood pressure (SBP) >= 130 mmHg or diastolic blood pressure
      (DBP) >= 80 mmHg or treatment with hypertensive medications. Logistic regression
      models and restricted cubic spline models were applied to evaluate the
      associations between dietary intakes of total, cereal, vegetable, and fruit fiber
      and hypertension. A total of 18,433 participants aged 18 years or older were
      included in the analyses. After adjustment for age, gender, body mass index
      (BMI), race, educational level, smoking status, family income, and total daily
      energy intake, compared with the lowest tertile, the odds ratios (95% confidence
      intervals) of hypertension for the highest tertile intakes of total, cereal,
      vegetable, and fruit fiber were 0.62 (0.52-0.75), 0.80 (0.67-0.96), 0.82 (0.69
      0.98), and 0.86 (0.71-1.04), respectively. Dose-response analyses revealed that
      the risk of hypertension was associated with total fiber intake in a nonlinear
      trend, while the relationships were linear for cereal and vegetable fiber
      intakes. Our results suggested that the intakes of total, cereal, and vegetable
      fiber, but not fruit fiber, were associated with a decreased risk of hypertension
      in U.S. adults.

PMID- 30111719
TI  - Evaluation of Nitrobenzyl Derivatives of Camptothecin as Anti-Cancer Agents and
      Potential Hypoxia Targeting Prodrugs.
AB  - As part of our initial efforts into developing a tumor-targeting therapy, C-10
      substituted derivatives of a camptothecin analog (SN-38) have been synthesized (2
      , 3- and 4-nitrobenzyl) for use as potential hypoxia-activated prodrugs and
      evaluated for their cytotoxicity, topoisomerase I inhibition and electrochemical
      (reductive) properties. All three derivatives were found to possess reduced
      toxicity towards human leukemia K562 cells compared to SN-38, validating a
      condition for prodrug action. Using an MTS assay, IC50's were found to be 3.0,
      25.9, 12.2 and 58.0 nM for SN-38, 2-nitro-, 3-nitro- and 4-nitrobenzyl-C10
      substituted-SN-38, respectively, representing an 8-, 4- and 19-fold decrease in
      cytotoxicity. Using a topoisomerase I assay, one of the analogs (4-nitrobenzyl)
      was shown to inhibit the ability of this enzyme to relax supercoiled pBR322 DNA,
      at a similar concentration to the clinically-approved active metabolite SN-38.
      Cyclic voltammetry detailed the reductive nature of the analogs, and was used to
      infer the potential of these compounds to serve as hypoxia-targeting prodrugs.
      The electrochemical results also validated the quasi-reversible nature of the
      first reduction step, and served as a proof-of-principle that hypoxia-targeting
      prodrugs of SN-38 can participate in a redox-futile cycle, the proposed mechanism
      of activation and targeting. Chemical reduction of the 4-nitrobenzyl analog led
      to the formation/release of SN-38 and validated the prodrug ability of the C-10
      substituted derivative.

PMID- 30111721
TI  - Label-Free Imaging of Melanoma with Confocal Photothermal Microscopy:
      Differentiation between Malignant and Benign Tissue.
AB  - Label-free confocal photothermal (CPT) microscopy was utilized for the first time
      to investigate malignancy in mouse skin cells. Laser diodes (LDs) with 405 nm or
      488 nm wavelengths were used as pumps, and a 638 nm LD was used as a probe for
      the CPT microscope. A Grey Level Cooccurrence Matrix (GLCM) for texture analysis
      was applied to the CPT images. Nine GLCM parameters were calculated with definite
      definitions for the intracellular super-resolved CPT images, and the parameters
      Entropy, Contrast, and Variance were found to be most suited among the nine
      parameters to discriminate clearly between healthy cells and malignant cells when
      a 405 nm pump was used. Prominence, Variance, and Shade were most suited when a
      pump wavelength of 488 nm was used.

PMID- 30111722
TI  - Impact of a Modified Version of Baby-Led Weaning on Dietary Variety and Food
      Preferences in Infants.
AB  - The aim of this study was to determine whether food variety and perceived food
      preferences differ in infants following baby-led instead of traditional spoon
      feeding approaches to introducing solids. A total of 206 women (41.3%
      primiparous) were recruited in late pregnancy from a single maternity hospital
      (response rate 23.4%) and randomized to Control (n = 101) or BLISS (n = 105)
      groups. All participants received government-funded Well Child care. BLISS
      participants also received support to exclusively breastfeed to 6 months and
      three educational sessions on BLISS (Baby-Led Weaning, modified to reduce the
      risk of iron deficiency, growth faltering, and choking) at 5.5, 7, and 9 months.
      Food variety was calculated from three-day weighed diet records at 7, 12, and 24
      months. Questionnaires assessed infant preference for different tastes and
      textures at 12 months, and for 'vegetables', 'fruit', 'meat and fish', or
      'desserts' at 24 months. At 24 months, 50.5% of participants provided diet record
      data, and 78.2% provided food preference data. BLISS participants had greater
      variety in 'core' (difference in counts over three days, 95% CI: 1.3, 0.4 to
      2.2), 'non-core' (0.6, 0.2 to 0.9), and 'meat and other protein' (1.3, 0.8 to
      1.9) foods at 7 months, and in 'fruit and vegetable' foods at 24 months (2, 0.4
      to 3.6). The only differences in perceived food preferences observed were very
      small (i.e., <5% difference in score, at 12 months only). Infants following the
      modified Baby-Led Weaning were exposed to more varied and textured foods from an
      early age, but only an increased variety in 'fruit and vegetable' intake was
      apparent by two years of age.

PMID- 30111724
TI  - Accurate Measurements of Wall Shear Stress on a Plate with Elliptic Leading Edge.
AB  - A micro-floating element wall shear stress sensor with backside connections has
      been developed for accurate measurements of wall shear stress under the turbulent
      boundary layer. The micro-sensor was designed and fabricated on a 10.16 cm SOI
      (Silicon on Insulator) wafer by MEMS (Micro-Electro-Mechanical System) processing
      technology. Then, it was calibrated by a wind tunnel setup over a range of 0 Pa
      to 65 Pa. The measurements of wall shear stress on a smooth plate were carried
      out in a 0.6 m * 0.6 m transonic wind tunnel. Flow speed ranges from 0.4 Ma to
      0.8 Ma, with a corresponding Reynold number of 1.05 * 106~1.55 * 106 at the micro
      sensor location. Wall shear stress measured by the micro-sensor has a range of
      about 34 Pa to 93 Pa, which is consistent with theoretical values. For
      comparisons, a Preston tube was also used to measure wall shear stress at the
      same time. The results show that wall shear stress obtained by three methods (the
      micro-sensor, a Preston tube, and theoretical results) are well agreed with each
      other.

PMID- 30111723
TI  - A Compositive Strategy to Study the Pharmacokinetics of TCMs: Taking Coptidis
      Rhizoma, and Coptidis Rhizoma-Glycyrrhizae Radix et Rhizoma as Examples.
AB  - Pharmacokinetic studies are crucial for elucidating the effective constituents
      and formula compatibility of traditional Chinese medicines (TCMs). However,
      studies have usually been limited to single dosages and detection of systemic
      blood concentrations. To obtain comprehensive pharmacokinetic information, here
      we propose a multi-dosage and multi-sampling (blood from portal vein or systemic
      circulation, and liver) strategy to comparatively study the pharmacokinetics of
      multi-form TCMs, i.e., pure constituents, TCMs, or TCM formula extracts. Based on
      this strategy, we studied the pharmacokinetics of pure berberine, berberine in
      CoptidisRhizoma (CRE), and berberine in CoptidisRhizoma-GlycyrrhizaeRadix
      etRhizoma extracts (CR-GRE). After simple calculation and comparison of the
      obtained area under the curve (AUC) values, the results revealed the drastically
      different pharmacokinetic properties of pure berberine compared to CRE and CR
      GRE. The results contribute to explaining the pharmacological loss of berberine
      activity after purification and the compatibility of the CR-GR drug pair. The
      results also innovatively showed that it was intestinal absorption that
      differentiated the pharmacokinetics of CRE and pure berberine, and CRE and CR
      GRE. In conclusion, we propose a composite strategy to comparatively study the
      pharmacokinetics of TCMs, which could provide sufficient information to obtain a
      comprehensive view, before follow-up mechanism-of-action studies.

PMID- 30111725
TI  - Allylation of Orthoquinones Towards Annulated Polycyclic Aromatic Systems.
AB  - Promising results of an efficient and convenient strategy for the annulation of
      polycyclic aromatic compounds (PACs), employing orthoquinones as starting
      material and comprising allylation, pinacol rearrangement, ring-closing
      metathesis (RCM), and one-pot reduction followed by Wagner-Meerwein
      rearrangement, are presented. The strategy involves introducing triallylborane
      prepared in situ in the allylation step. Moreover, a novel expedient method for
      the preparation of 9,10-diallylphenanthrene was introduced.

PMID- 30111726
TI  - Alterations in the MicroRNA of the Blood of Autism Spectrum Disorder Patients:
      Effects on Epigenetic Regulation and Potential Biomarkers.
AB  - Aims: Autism spectrum disorder (ASD) refers to a group of heterogeneous brain
      based neurodevelopmental disorders with different levels of symptom severity.
      Given the challenges, the clinical diagnosis of ASD is based on information
      gained from interviews with patients' parents. The heterogeneous pathogenesis of
      this disorder appears to be driven by genetic and environmental interactions,
      which also plays a vital role in predisposing individuals to ASD with different
      commitment levels. In recent years, it has been proposed that epigenetic
      modifications directly contribute to the pathogenesis of several
      neurodevelopmental disorders, such as ASD. The microRNAs (miRNAs) comprises a
      species of short noncoding RNA that regulate gene expression post
      transcriptionally and have an essential functional role in the brain,
      particularly in neuronal plasticity and neuronal development, and could be
      involved in ASD pathophysiology. The aim of this study is to evaluate the
      expression of blood miRNA in correlation with clinical findings in patients with
      ASD, and to find possible biomarkers for the disorder. Results: From a total of
      26 miRNA studied, seven were significantly altered in ASD patients, when compared
      to the control group: miR34c-5p, miR92a-2-5p, miR-145-5p and miR199a-5p were up
      regulated and miR27a-3p, miR19-b-1-5p and miR193a-5p were down-regulated in ASD
      patients. Discussion: The main targets of these miRNAs are involved in
      immunological developmental, immune response and protein synthesis at
      transcriptional and translational levels. The up-regulation of both miR-199a-5p
      and miR92a-2a and down-regulation of miR-193a and miR-27a was observed in AD
      patients, and may in turn affect the SIRT1, HDAC2, and PI3K/Akt-TSC:mTOR
      signaling pathways. Furthermore, MeCP2 is a target of miR-199a-5p, and is
      involved in Rett Syndrome (RTT), which possibly explains the autistic phenotype
      in male patients with this syndrome.

PMID- 30111727
TI  - Enhanced Oxygen Vacancies in a Two-Dimensional MnAl-Layered Double Oxide Prepared
      via Flash Nanoprecipitation Offers High Selective Catalytic Reduction of NOx with
      NH3.
AB  - A two-dimensional MnAl-layered double oxide (LDO) was obtained by flash
      nanoprecipitation method (FNP) and used for the selective catalytic reduction of
      NOx with NH3. The MnAl-LDO (FNP) catalyst formed a particle size of 114.9 nm.
      Further characterization exhibited rich oxygen vacancies and strong redox
      property to promote the catalytic activity at low temperature. The MnAl-LDO (FNP)
      catalyst performed excellent NO conversion above 80% at the temperature range of
      100-400  degrees C, and N2 selectivity above 90% below 200  degrees C, with a gas
      hourly space velocity (GHSV) of 60,000 h-1, and a NO concentration of 500 ppm.
      The maximum NO conversion is 100% at 200  degrees C; when the temperature in 150
      250  degrees C, the NO conversion can also reach 95%. The remarkable low
      temperature catalytic performance of the MnAl-LDO (FNP) catalyst presented
      potential applications for controlling NO emissions on the account of the
      presentation of oxygen vacancies.

PMID- 30111728
TI  - Quality of Prenatal and Childhood Diet Predicts Neurodevelopmental Outcomes among
      Children in Mexico City.
AB  - Adequate nutrition is important for neurodevelopment. Although nutrients are
      ingested in combination, the impact of specific nutrients within the context of a
      nutrient mixture has not been studied with respect to health, such as
      neurodevelopment. Therefore, we examined the impact of prenatal and childhood
      nutrient mixtures on neurodevelopmental outcomes. Participants included mother
      child pairs in the Programming Research in Obesity, Growth, Environment, and
      Social Stress (PROGRESS) prospective birth cohort in Mexico City. We assessed
      prenatal and child micro- and macronutrient profiles among 65 and 329 children,
      respectively, via food frequency questionnaires. Neurodevelopmental outcomes of 4
      6-year-old children were measured using the McCarthy Scales of Children's
      Abilities (MSCA). We conducted weighted quantile sum (WQS) regression analyses to
      calculate indices reflecting "good" and "poor" prenatal and childhood nutrition.
      After adjusting for maternal education, socioeconomic status, the Home
      Observation for Measurement of the Environment (HOME) score, and total caloric
      intake, the good prenatal and childhood nutrition indices predicted more
      favorable neurodevelopment, while both poor nutrition indices predicted poorer
      neurodevelopment. These associations were stronger in prenatal than childhood
      models. Monounsaturated fats predicted various neurodevelopmental abilities
      relatively strongly in both models. Prenatal and childhood consumption of
      combinations of beneficial nutrients may contribute to more favorable
      neurodevelopment.

PMID- 30111729
TI  - Transesterification of Lactic Acid Oligomers with Ethanol, a Way to Anhydrous
      Ethyl Lactate: A Kinetic Study.
AB  - A new method for the preparation of anhydrous ethyl ester of lactic acid was
      studied. The selected method is based on catalytic transesterification of lactic
      acid oligomers, which were prepared for this purpose by autocatalytic
      oligomerization of lactic acid. In this work, a kinetic model for the case of
      catalytic alcoholysis of oligoesters was derived assuming a first-order reaction
      and equimolar content of reactants in the reaction mixture. The model makes it
      possible to obtain the values of the reaction rate and equilibrium constants and
      the equilibrium alcohol concentration by regression analysis at one time. The
      model was verified by measuring the rate of consumption of ethanol over the time
      at various reaction temperatures with anhydrous FeCl3 as the catalyst. The
      reaction was studied at overpressure under autogenous conditions in the
      temperature range of 100-180  degrees C. For the catalyst concentration of 1 mol
      %, the activation energy value was 64.35 kJ.mol-1. The dependence of equilibrium
      composition and rate constant on the temperature was obtained. The derived model
      is generally applicable to all first-order equilibrium reactions. The presumption
      is that the forward and reverse reactions are of the same order and have the same
      stoichiometry and equivalent amounts of reactants at the beginning of the
      reaction.

PMID- 30111731
TI  - Retained Austenite Decomposition and Carbide Precipitation during Isothermal
      Tempering of a Medium-Carbon Low-Alloy Bainitic Steel.
AB  - The effect of isothermal tempering on retained austenite decomposition and
      carbide precipitation were investigated in a medium-carbon low-alloy bainitic
      steel. High-resolution dilatometry was used to perform isothermal tempering at
      350  degrees C, 550  degrees C and 600  degrees C for different holding times up
      to 16 h. The decomposition of retained austenite, morphology and composition of
      carbides were investigated by analyzing the dilatometric curves and were
      confirmed through scanning and transmission electron microscopy observations. The
      decomposition behavior of retained austenite varied significantly as a function
      of the tempering temperature with a full decomposition observed at 600  degrees
      C. It was also found that by increasing the tempering temperature from 550 
      degrees C to 600  degrees C, carbides precipitate approximately twice as fast,
      and evolve from M3C type to Cr7C3 and Cr23C6 after 16 h of tempering at 600 
      degrees C.

PMID- 30111730
TI  - An Evaluation of Two Different Broiler Catching Methods.
AB  - Catching is the first step in the pre-slaughter chain for broiler chickens. The
      process may be detrimental for animal welfare due to the associated handling. The
      aim of this pilot study was to compare two different methods to manually catch
      broilers: Catching the broilers by two legs and carrying them inverted (LEGS) or
      catching the broilers under the abdomen and carrying them in an upright position
      (UPRIGHT). Wing and leg fractures upon arrival at the abattoir, animal density in
      the drawers, birds on their back, broilers dead-on-arrival and time to fill the
      transport modules were investigated. The results showed that mean crating time
      was shorter in the UPRIGHT method (p = 0.007). There was a tendency for more wing
      fractures in broilers caught by the LEGS (p = 0.06). The animal density in the
      drawers was lower and with a smaller range in the UPRIGHT method (p = 0.022). The
      results indicate that catching the broilers under the abdomen in an upright
      position may improve broiler welfare in terms of fewer wing fractures, more
      consistent stocking density in drawers and potentially reduced loading time.

PMID- 30111732
TI  - A Trusted Lightweight Communication Strategy for Flying Named Data Networking.
AB  - Flying Ad hoc Network (FANET) is a new resource-constrained breed and
      instantiation of Mobile Ad hoc Network (MANET) employing Unmanned Aerial Vehicles
      (UAVs) as communicating nodes. These latter follow a predefined path called
      'mission' to provide a wide range of applications/services. Without loss of
      generality, the services and applications offered by the FANET are based on
      data/content delivery in various forms such as, but not limited to, pictures,
      video, status, warnings, and so on. Therefore, a content-centric communication
      mechanism such as Information Centric Networking (ICN) is essential for FANET.
      ICN addresses the problems of classical TCP/IP-based Internet. To this end,
      Content-centric networking (CCN), and Named Data Networking (NDN) are two of the
      most famous and widely-adapted implementations of ICN due to their intrinsic
      security mechanism and Interest/Data-based communication. To ensure data
      security, a signature on the contents is appended to each response/data packet in
      transit. However, trusted communication is of paramount importance and currently
      lacks in NDN-driven communication. To fill the gaps, in this paper, we propose a
      novel trust-aware Monitor-based communication architecture for Flying Named Data
      Networking (FNDN). We first select the monitors based on their trust and
      stability, which then become responsible for the interest packets dissemination
      to avoid broadcast storm problem. Once the interest reaches data producer, the
      data comes back to the requester through the shortest and most trusted path
      (which is also the same path through which the interest packet arrived at the
      producer). Simultaneously, the intermediate UAVs choose whether to check the data
      authenticity or not, following their subjective belief on its producer's behavior
      and thus-forth reducing the computation complexity and delay. Simulation results
      show that our proposal can sustain the vanilla NDN security levels exceeding the
      80% dishonesty detection ratio while reducing the generated end-to-end delay to
      less than 1 s in the worst case and reducing the average consumed energy by more
      than two times.

PMID- 30111734
TI  - Ecofriendly Palladium on Wool Nanocatalysts for Cyclohexene Hydrogenation.
AB  - Use of natural wool fiber supports in the fabrication of novel composite
      materials incorporating metal nanoparticles, which offer the possibility of
      "environmentally friendly" catalytic materials, has been investigated. The
      catalytic hydrogenation of cyclohexene to cyclohexane by palladium nanoparticles
      immobilized on wool (Pd/wool) was studied using moderate pressure of pure
      hydrogen gas. The performance of wool-supported catalysts was explored over a
      palladium nanoparticle loading ranging from 1.6 to 2.6 wt %. The effect of the
      catalytic testing conditions, including stirring rate, amount of reactants, gas
      pressure, and target temperature were explored. A systematic series of catalytic
      activity tests carried out at 400 psi H2 for 5 and 24 h reaction times at 40 
      degrees C using a stirring rate 750 rpm allowed us to identify differences in
      performance within the series of Pd/wool nanocatalysts studied. The most
      catalytically active samples contained Pd nanoparticles with average sizes of ca.
      5 nm located predominantly on the surface and within the topmost layer of wool
      fibers, making them more accessible to the reactants.

PMID- 30111737
TI  - Variations in Dissolved Nitrate, Chloride, and Sulfate in Precipitation,
      Reservoir, and Tap Waters, Columbus, Ohio.
AB  - Urban potable waters can be very susceptible to human activities that can impact
      water quality and, hence, public health. Columbus, Ohio, is currently the 14th
      largest city in the United States with an estimated population of ~860,000. Much
      of the urban population receives its water supply from a series of reservoirs
      located north of the city proper. These reservoirs are fed by river systems that
      drain either large agricultural lands, or rapidly growing suburban areas, or
      both. The agricultural activities introduce dissolved nitrate, and increased
      usage of de-icing salts on roads and highways within the drainage area introduce
      chloride into the river/reservoir systems. High nitrate in drinking water poses a
      potential health risk, particularly to infants, while high chloride, applied as
      halite, in drinking water can aid in the development of cardiovascular disease.
      In this work, we present a 19-month time series measuring nitrate, chloride, and
      sulfate in local precipitation, reservoir and household tap waters in order to
      better understand the relationship of the hydrologic residence time on the tap
      water chemistry, as well as to evaluate the anion concentrations. The highest
      chloride tap water concentration, 6.9 mM, occurred in early February 2011, while
      increases in nitrate occurred in both early summer and the middle of winter. In
      general, the anion concentrations in the precipitation are all equal to or lower
      than the reservoir waters. Similarly, the tap water had concentrations of
      chloride and sulfate higher than reservoir water, while nitrate was similar to
      reservoir water. Tap water had higher fluoride and sulfate concentrations,
      suggesting that they are added during the treatment of the reservoir water prior
      to residential distribution. These data clearly demonstrate the importance of
      watershed lands on the quality of water in the human distribution system.

PMID- 30111736
TI  - Replication of Micro- and Nanofeatures in Injection Molding of Two PLA Grades
      with Rapid Surface-Temperature Modulation.
AB  - The production by injection molding of polymeric components having micro- and
      nanometrical surfaces is a complex task. Generally, the accurate replication of
      micro- and nanometrical features on the polymeric surface during the injection
      molding process is prevented by of the low mold temperature adopted to reduce
      cooling time. In this work, we adopt a system that allows fast heating of the
      cavity surface during the time the melt reaches the cavity, and fast cooling
      after heater deactivation. A nickel insert with micro- and nanofeatures in relief
      is located on the cavity surface. Replication accuracy is analyzed by Atomic
      Force Microscopy under different injection-molding conditions. Two grades of
      polylactic acid with different viscosity have been adopted. The results indicate
      that the higher the cavity surface temperature is, the higher the replication
      accuracy is. The viscosity has a significant effect only in the replication of
      the microfeatures, whereas its effect results are negligible in the replication
      of nanofeatures, thus suggesting that the interfacial phenomena are more
      important for replication at a nanometric scale. The evolution of the
      crystallinity degree on the surface also results in a key factor on the
      replication of nanofeatures.

PMID- 30111735
TI  - New Ansamycins from the Deep-Sea-Derived Bacterium Ochrobactrum sp. OUCMDZ-2164.
AB  - Two new ansamycins, trienomycins H (1) and I (2), together with the known
      trienomycinol (3), were isolated from the fermentation broth of the deep-sea
      derived bacterium Ochrobactrum sp. OUCMDZ-2164. Their structures, including their
      absolute configurations, were elucidated based on spectroscopic analyses, ECD
      spectra, and Marfey's method. Compound 1 exhibited cytotoxic effects on A549 and
      K562 cell lines with IC50 values of 15 and 23 MUM, respectively.

PMID- 30111733
TI  - Proteome-Wide Analysis of Trypanosoma cruzi Exponential and Stationary Growth
      Phases Reveals a Subcellular Compartment-Specific Regulation.
AB  - Trypanosoma cruzi, the etiologic agent of Chagas disease, cycles through
      different life stages characterized by defined molecular traits associated with
      the proliferative or differentiation state. In particular, T. cruzi epimastigotes
      are the replicative forms that colonize the intestine of the Triatomine insect
      vector before entering the stationary phase that is crucial for differentiation
      into metacyclic trypomastigotes, which are the infective forms of mammalian
      hosts. The transition from proliferative exponential phase to quiescent
      stationary phase represents an important step that recapitulates the early
      molecular events of metacyclogenesis, opening new possibilities for understanding
      this process. In this study, we report a quantitative shotgun proteomic analysis
      of the T. cruzi epimastigote in the exponential and stationary growth phases.
      More than 3000 proteins were detected and quantified, highlighting the regulation
      of proteins involved in different subcellular compartments. Ribosomal proteins
      were upregulated in the exponential phase, supporting the higher replication rate
      of this growth phase. Autophagy-related proteins were upregulated in the
      stationary growth phase, indicating the onset of the metacyclogenesis process.
      Moreover, this study reports the regulation of N-terminally acetylated proteins
      during growth phase transitioning, adding a new layer of regulation to this
      process. Taken together, this study reports a proteome-wide rewiring during T.
      cruzi transit from the replicative exponential phase to the stationary growth
      phase, which is the preparatory phase for differentiation.

PMID- 30111738
TI  - Brain Health across the Lifespan: A Systematic Review on the Role of Omega-3
      Fatty Acid Supplements.
AB  - The brain is the most significant and complex organ of the human body.
      Increasingly, we are becoming aware that certain nutrients may help to safeguard
      brain health. An expanse of research has investigated the effects of omega fatty
      acids in relation to brain health but effects across the lifespan have not been
      widely evaluated. The present systematic review collated evidence from 25
      randomized controlled trials (n = 3633) published since 2013. Compared with
      control groups, omega-3 supplementation generally correlated with improvements in
      blood biomarkers. Subsequently, these appear to benefit those with lower baseline
      fatty acid levels, who are breastfeeding or who have neuropsychiatric conditions.
      Whilst multiple studies indicate that omega fatty acids can protect against
      neurodegeneration in older adults, more work is needed in the years preceding the
      diagnosis of such medical conditions. Bearing in mind the scale of ageing
      populations and rising healthcare costs linked to poor brain health, omega
      supplementation could be a useful strategy for helping to augment dietary intakes
      and support brain health across the lifespan. Ongoing research is now needed
      using harmonious methodologies, supplement dosages, ratios and intervention
      periods to help formulate congruent conclusions.

PMID- 30111739
TI  - The Trade-Off between Optimizing Flight Patterns and Human Health: A Case Study
      of Aircraft Noise in Queens, NY, USA.
AB  - Objectives: Airports in the U.S. have gradually been transitioning to automated
      flight systems. These systems generate new flight paths over populated areas.
      While they can improve flight efficiency, the increased noise associated with
      these novel flight patterns potentially pose serious health threats to the
      overflown communities. In this case study, we estimated the monetary benefits
      relative to health losses associated with one significant change in flight
      patterns at LaGuardia Airport, year-round use of "TNNIS Climb", which happened in
      2012 as a result of flight automation in New York City. Prior to that, the use of
      the TNNIS Climb was limited to the U.S. Open tennis matches. Methods: We
      developed a decision-analytic model using Markov health states to compare the
      costs and quality-adjusted life years (QALYs) gained associated with the limited
      use of TNNIS (old status quo) and the year-round use of TNNIS (current status
      quo). The TNNIS Climb increases airplane noise to above 60 decibels (dB) over
      some of the most densely populated areas of the city. We used this increased
      exposure to noise as the basis for estimating ground-level health using data from
      sound monitors. The total costs (including both direct and indirect costs),
      QALYs, and the incremental cost-effectiveness ratio (ICER) were estimated for the
      limited versus the year-round use of the TNNIS Climb. Results: The incremental
      lifetime costs and QALYs per person exposed to noise associated with the limited
      versus the year-round use of TNNIS was $11,288, and 1.13, respectively.
      Therefore, the limited use of TNNIS had an ICER of $10,006/QALY gained relative
      to the year-round of TNNIS. Our analyses were robust to changes in assumptions
      and data inputs. Conclusions: Despite increases in efficiency, flight automation
      systems without a careful assessment of noise might generate flight paths over
      densely populated areas and cause serious health conditions for the overflown
      communities.

PMID- 30111740
TI  - Interaction between Parental Education and Household Wealth on Children's Obesity
      Risk.
AB  - Parents' education and household wealth cannot be presumed to operate
      independently of each other. However, in traditional studies on the impact of
      social inequality on obesity, education and financial wealth tend to be viewed as
      separable processes. The present study examines the interaction of parents'
      education and household wealth in relation to childhood obesity. Anthropometric
      measurement and questionnaire surveys were carried out on 3670 children (aged 9
      12 years) and their parents from 26 elementary schools in northeast China.
      Results showed that the interaction term was significant for household wealth and
      father's education (p < 0.01), while no significant interaction between household
      wealth and mother's education was found. In a separate analysis, the interaction
      was statistically significant among girls for obesity risk based on BMI (p =
      0.02), and among urban children for both obesity risk based on BMI (p = 0.01) and
      abdominal obesity risk based on WHR (p = 0.03). Specifically, when household
      wealth increased from the first quintile to the fifth quintile, OR for father's
      education decreased from higher than 1 (OR = 1.95; 95% CI: 1.12-3.38) to non
      significant for girl's obesity risk, from non-significant to lower than 1 for
      urban children's obesity risk (OR = 0.52; 95% CI: 0.32-0.86 for the fourth
      quintile; OR = 0.37; 95% CI: 0.19-0.73 for the fifth quintile) and from higher
      than 1 (OR = 1.61; 95% CI: 1.04-2.05) to non-significant for urban children's
      abdominal obesity risk. These findings indicate that father's education level
      interacts with household wealth to influence obesity among girls and urban
      children in northeast China.

PMID- 30111741
TI  - Correlation between Non-Polio Acute Flaccid Paralysis Rates with Pulse Polio
      Frequency in India.
AB  - The last case of polio from India was reported in 2011. That year, the non-polio
      acute flaccid paralysis (NPAFP) rate in India was 13.35/100,000, where the
      expected rate is 1-2/100,000. A previous study of data from 2000 to 2010 has
      detailed the NPAFP rate in a state correlated with the pulse polio rounds
      conducted there, and the strongest correlation with the NPAFP rate was found when
      the number of doses from the previous 4 years were used. However, a simple
      association being found with regression analysis does not prove a causal
      relationship. After publication of those findings, as the threat of polio had
      lessened, the number of rounds of OPV administration was brought down. The
      present study has been done to look at data till the end of 2017, to see if the
      incidence of NPAFP declined with this reduction in polio immunization rounds. We
      used polio surveillance data acquired by the Government of India from 2000-2017.
      Correlation of the NAFP rate to the number of polio rounds in the state was
      examined, and the cumulative effect of polio doses administered in previous years
      was sought. NPAFP rate correlated with the OPV pulse polio rounds in that year (R
      = 0.46; p < 0.001), and the NPAFP rate started to decrease from 2012 when the
      number of pulse polio rounds had decreased. NPAFP rates in the states of Uttar
      Pradesh (UP) and Bihar were the highest in the country. Looking at the high-NPAFP
      states of UP and Bihar, we found that the correlation coefficient was strongest
      when doses used over 5 years was considered (R = 0.76; p < 0.001). The response
      to the reduction in OPV rounds (de-challenging) adds credence to the assumption
      that OPV was responsible for the change in the NPAFP rate. Now that India has
      been polio-free for over 6 years, we propose that we may be able to reduce NPAFP
      by further reducing pulse polio rounds.

PMID- 30111742
TI  - A Physically Based Constitutive Model and Continuous Dynamic Recrystallization
      Behavior Analysis of 2219 Aluminum Alloy during Hot Deformation Process.
AB  - The isothermal compression tests of the 2219 Al alloy were conducted at the
      temperature and the strain rate ranges of 623-773 K and 0.01-10 s-1,
      respectively, and the deformed microstructures were observed. The flow curves of
      the 2219 Al alloy obtained show that flow stress decreases with the increase in
      temperature and/or the decrease in strain rate. The physically based constitutive
      model is applied to describe the flow behavior during hot deformation. In this
      model, Young's modulus and lattice diffusion coefficient are temperature
      dependent, and the creep exponent is regarded as a variable. The predicted values
      calculated by the constitutive model are in good agreement with the experimental
      results. In addition, it is confirmed that the main softening mechanism of the
      2219 Al alloy during hot deformation is dynamic recovery and incomplete
      continuous dynamic recrystallization (CDRX) by the analysis of electron
      backscattered diffraction (EBSD) micrographs. Moreover, CDRX can readily occur
      under the condition of high temperatures, low strain rates, and large strains.
      Meanwhile, the recrystallization grain size will also be larger.

PMID- 30111743
TI  - Combination ART-Induced Oxidative/Nitrosative Stress, Neurogenic Inflammation and
      Cardiac Dysfunction in HIV-1 Transgenic (Tg) Rats: Protection by Mg.
AB  - Chronic effects of a combination antiretroviral therapy (cART =
      tenofovir/emtricitatine + atazanavir/ritonavir) on systemic and cardiac oxidative
      stress/injury in HIV-1 transgenic (Tg) rats and protection by Mg-supplementation
      were assessed. cART (low doses) elicited no significant effects in normal rats,
      but induced time-dependent oxidative/nitrosative stresses: 2.64-fold increased
      plasma 8-isoprostane, 2.0-fold higher RBC oxidized glutathione (GSSG), 3.2-fold
      increased plasma 3-nitrotyrosine (NT), and 3-fold elevated basal neutrophil
      superoxide activity in Tg rats. Increased NT staining occurred within cART
      treated HIV-Tg hearts, and significant decreases in cardiac systolic and
      diastolic contractile function occurred at 12 and 18 weeks. HIV-1 expression
      alone caused modest levels of oxidative stress and cardiac dysfunction.
      Significantly, cART caused up to 24% decreases in circulating Mg in HIV-1-Tg
      rats, associated with elevated renal NT staining, increased creatinine and urea
      levels, and elevated plasma substance P levels. Strikingly, Mg-supplementation (6
      fold) suppressed all oxidative/nitrosative stress indices in the blood, heart and
      kidney and substantially attenuated contractile dysfunction (>75%) of cART
      treated Tg rats. In conclusion, cART caused significant renal and cardiac
      oxidative/nitrosative stress/injury in Tg-rats, leading to renal Mg wasting and
      hypomagnesemia, triggering substance P-dependent neurogenic inflammation and
      cardiac dysfunction. These events were effectively attenuated by Mg
      supplementation likely due to its substance P-suppressing and Mg's intrinsic anti
      peroxidative/anti-calcium properties.

PMID- 30111744
TI  - Environmental Impacts of Engineered Nanomaterials-Imbalances in the Safety
      Assessment of Selected Nanomaterials.
AB  - For this Editorial, we, the guest editors, performed a brief review with the aim
      of setting the framework for the Special issue on the "Environmental Impacts of
      Nanomaterials" [...].

PMID- 30111745
TI  - The Efficacy of Buprenorphine in Major Depression, Treatment-Resistant Depression
      and Suicidal Behavior: A Systematic Review.
AB  - Although several pharmacological options to treat depression are currently
      available, approximately one third of patients who receive antidepressant
      medications do not respond adequately or achieve a complete remission. Thus,
      novel strategies are needed to successfully address those who did not respond, or
      partially respond, to available antidepressant pharmacotherapy. Research findings
      revealed that the opioid system is significantly involved in the regulation of
      mood and incentives salience and may be an appropriate target for novel
      therapeutic agents. The present study aimed to systematically review the current
      literature about the use of buprenorphine (BUP) for major depression, treatment
      resistant depression (TRD), non-suicidal self-injury (NSSI) behavior, and
      suicidal behavior. We investigated Pubmed and Scopus databases using the
      following keywords: "buprenorphine AND depression", "buprenorphine AND treatment
      resistant depression", "buprenorphine AND suicid*", "buprenorphine AND refractory
      depression". Several evidence demonstrate that, at low doses, BUP is an
      efficacious, well-tolerated, and safe option in reducing depressive symptoms,
      serious suicidal ideation, and NSSI, even in patients with TRD. However, more
      studies are needed to evaluate the long-term effects, and relative efficacy of
      specific combinations (e.g., BUP + samidorphan (BUP/SAM), BUP + naloxone
      (BUP/NAL), BUP + naltrexone) over BUP monotherapy or adjunctive BUP treatment
      with standard antidepressants, as well as to obtain more uniform guidance about
      the optimal BUP dosing interval.

PMID- 30111746
TI  - The Role of Direct Oral Anticoagulants in Treatment of Cancer-Associated
      Thrombosis.
AB  - Venous thromboembolism (VTE) complicates the clinical course of approximately 5
      10% of all cancer patients. Anticoagulation of the cancer patient often presents
      unique challenges as these patients have both a higher risk of recurrent VTE and
      a higher risk of bleeding than patients without cancer. Although low molecular
      weight heparins (LMWH) are the standard of care for the management of cancer
      associated VTE, their use requires once or twice daily subcutaneous injections,
      which can be a significant burden for many cancer patients who often require a
      long duration of anticoagulation. The direct oral anticoagulants (DOACs) are
      attractive options for patients with malignancy. DOACs offer immediate onset of
      action and short half-lives, properties similar to LMWH, but the oral route of
      administration is a significant advantage. Given the higher risks of recurrent
      VTE and bleeding, there has been concern about the efficacy and safety of DOACs
      in this patient population. Data are now emerging for the use of DOACs in the
      cancer patient population from dedicated clinical trials. While recently
      published data suggest that DOACs hold promise for the treatment of cancer
      associated VTE, additional studies are needed to establish DOACs as the standard
      of-care treatment. Many such studies are currently underway. The available data
      for the use of DOACs in the treatment of cancer-associated VTE will be reviewed,
      focusing on efficacy, safety, and other considerations relevant to the cancer
      patient.

PMID- 30111748
TI  - Is TAK1 a Direct Upstream Kinase of AMPK?
AB  - Alongside Liver kinase B1 (LKB1) and Ca2+/Calmodulin-dependent protein kinase
      kinase 2 (CaMKK2), Transforming growth factor-beta (TGF-beta)-activated kinase 1
      (TAK1) has been suggested as a direct upstream kinase of AMP-activated protein
      kinase (AMPK). Several subsequent studies have reported on the TAK1-AMPK
      relationship, but the interpretation of the respective data has led to
      conflicting views. Therefore, to date the acceptance of TAK1 as a genuine AMPK
      kinase is lagging behind. This review provides with argumentation, whether or not
      TAK1 functions as a direct upstream kinase of AMPK. Several specific open
      questions that may have precluded the consensus are discussed based on available
      data. In brief, TAK1 can function as direct AMPK upstream kinase in specific
      contexts and in response to a subset of TAK1 activating stimuli. Further research
      is needed to define the intricate signals that are conditional for TAK1 to
      phosphorylate and activate AMPKalpha at T172.

PMID- 30111749
TI  - A Comprehensive Quality Evaluation Method Based on C30-HPLC and an Analytic
      Hierarchy Process for the Chinese Herbal Formula, Erzhiwan.
AB  - The quantitative analysis of multiple indexes remains an important quality
      evaluation method of traditional Chinese medicine (TCM) herbal formulas. The
      Chinese Pharmacopoeia 2015 only stipulates the content of a single component,
      specnuezhenide, in Erzhiwan composed of the Fructus Ligustri Lucidi (FLL) powder
      and aqueous extracts of Herba Ecliptae (HE). To generalize the intrinsic quality
      of Erzhiwan, a novel C30-HPLC method with good precision, accuracy, and
      reproducibility was developed for the simultaneous determination of six
      compounds, including two isomers, and then an analytic hierarchy process was
      further applied to integrate and discriminate the quality of four samples
      prepared via different methods. The results of the analysis were in agreement
      with the antioxidant tests in vitro. This comprehensive strategy could provide a
      reference and suggestions for the improvement of the quality evaluation method of
      TCM herbal formulas.

PMID- 30111751
TI  - Primary Signet Ring Cell Carcinoma of the Prostate: A Rare Case Report.
AB  - Primary prostatic signet ring cell carcinoma is a rare form of cancer with a poor
      prognosis, which is generally treated with a traditional prostate adenocarcinoma
      therapy. This case report presents a 70-year-old diagnosed with primary prostatic
      signet ring cell carcinoma, treated with a combination of radiotherapy and
      hormone therapy and a 16 month survival without an evidence of the disease at
      follow up.

PMID- 30111750
TI  - Antimicrobial Usage in Animal Production: A Review of the Literature with a Focus
      on Low- and Middle-Income Countries.
AB  - Antimicrobial use (AMU) in animal production is a key contributor to
      antimicrobial resistance (AMR) worldwide. As consumption of animal protein and
      associated animal production is forecast to increase markedly over coming years
      in low- and middle-income countries (LMICs), accurate monitoring of AMU has
      become imperative. We summarized data from 89 scientific studies reporting AMU
      data in animal production published in English since 1998, identified through the
      'ISI Web of Knowledge' search engine. The aims were as follows: (a) to describe
      methodologies and metrics used to quantify AMU; (b) to summarize qualitative (on
      farm prevalence of use) and quantitative (amounts of antimicrobial active
      principle) data, in order to identify food animal species at the highest risk of
      AMU; and (c) to highlight data gaps from LMICs. Only 17/89 (19.1%) studies were
      conducted in LMICs. Sixty (67.3%) reported quantitative data use, with 'daily
      doses per animal-time' being the most common metric. AMU was greatest in chickens
      (138 doses/1000 animal-days [inter quartile range (IQR) 91.1-438.3]), followed by
      swine (40.2 [IQR 8.5-120.4]), and dairy cattle (10.0 [IQR 5.5-13.6]). However,
      per kg of meat produced, AMU was highest in swine, followed by chickens and
      cattle. Our review highlights a large deficit of data from LMICs, and provides a
      reference for comparison with further surveillance and research initiatives
      aiming to reduce AMU in animal production globally.

PMID- 30111754
TI  - Practical Approach for High-Resolution Airport Pavement Inspection with the
      Yakumo Multistatic Array Ground-Penetrating Radar System.
AB  - It is important to identify the thin cracks within the airport pavement layers.
      To achieve this goal, a practical interferometric approach using the Yakumo
      multistatic ground-penetrating radar system was developed to detect the slight
      variability in wave propagation velocity and/or thickness caused by the thin
      cracks. In comparison with the conventional common midpoint (CMP) velocity
      estimation method, the proposed method can provide much higher-resolution
      estimations of slight deviations in the velocity and thickness from their
      corresponding reference values in the undamaged asphalt through the comparison of
      two CMP datasets. These deviations can be obtained analytically instead of
      graphically extracted from the CMP velocity spectrum. The proposed approach was
      not only analyzed using the simulated datasets, but also practically demonstrated
      at both an experimental model site and an actual airport site. In the simulation
      tests, velocity deviations on the order of a few millimeters per nanosecond were
      detected, and the experimental results shows good agreement with the ground truth
      and coring samples. This method provides a novel way to inspect partially damaged
      pavement when the thin cracks are difficult to detect using the reflected
      signals.

PMID- 30111753
TI  - A Low-Cost, Stand-Alone Sensory Platform for Monitoring Extreme Solar
      Overirradiance Events.
AB  - In this paper, we present a low-cost, stand-alone sensory platform developed for
      in situ monitoring of environmental parameters, for use in the Amazon region in
      the north of Brazil. The mission of the platform is to perform monitoring and
      identification of overirradiance (solar irradiance > 1000 W/m2) and extreme
      overirradiance events (solar irradiance > 1300 W/m2) using a photovoltaic based
      irradiance sensor. The sensory platform was built using the ESP8266
      microcontroller, an open embedded computer capable of Wi-Fi communication using
      the IEEE 802.11 standard, and small photovoltaic modules, air temperature,
      atmospheric pressure, voltage, and current sensors, enabling the development of a
      low-cost system (?70/R$350.00 BRL). Calibration and tests were conducted at the
      Federal University of Para (UFPA), Belem campus, Para, where the platform
      measured an extreme overirradiance of 1321 W/m2 at a low-latitude (1  degrees S)
      and low altitude (7 m above sea level).

PMID- 30111747
TI  - Molecular Signatures of the Insulin-like Growth Factor 1-mediated Epithelial
      Mesenchymal Transition in Breast, Lung and Gastric Cancers.
AB  - The insulin-like growth factor (IGF) system, which is constituted by the IGF-1
      and IGF-2 peptide hormones, their corresponding receptors and several IGF binding
      proteins, is involved in physiological and pathophysiological processes. The IGF
      system promotes cancer proliferation/survival and its signaling induces the
      epithelial-mesenchymal transition (EMT) phenotype, which contributes to the
      migration, invasiveness, and metastasis of epithelial tumors. These cancers share
      two major IGF-1R signaling transduction pathways, PI3K/AKT and RAS/MEK/ERK.
      However, as far as we could review at this time, each type of cancer cell
      undergoes EMT through tumor-specific routes. Here, we review the tumor-specific
      molecular signatures of IGF-1-mediated EMT in breast, lung, and gastric cancers.

PMID- 30111752
TI  - Combination Effect of Silver Nanoparticles and Histone Deacetylases Inhibitor in
      Human Alveolar Basal Epithelial Cells.
AB  - Although many treatment strategies have been reported for lung disease, the
      mechanism of combination therapy using silver nanoparticles (AgNPs) and histone
      deacetylases inhibitors (HDACi) remains unclear. Therefore, innovative treatment
      strategies are essential for addressing the therapeutic challenges of this highly
      aggressive lung cancer. AgNPs and HDACi seem to be the best candidates for
      anticancer therapy because of their anti-proliferative effect in a variety of
      cancer cells. First, we synthesized AgNPs using wogonin as a reducing and
      stabilizing agent, following which the synthesized AgNPs were characterized by
      various analytical techniques. The synthesized AgNPs exhibited dose- and size
      dependent toxicity towards A549 cells. Interestingly, the combination of AgNPs
      and MS-275 significantly induces apoptosis, which was accompanied by an increased
      level of reactive oxygen species (ROS); leakage of lactate dehydrogenase (LDH);
      secretion of TNFalpha; dysfunction of mitochondria; accumulation autophagosomes;
      caspase 9/3 activation; up and down regulation of pro-apoptotic genes and anti
      apoptotic genes, respectively; and eventually, induced DNA-fragmentation. Our
      findings suggest that AgNPs and MS-275 induce cell death in A549 lung cells via
      the mitochondrial-mediated intrinsic apoptotic pathway. Finally, our data show
      that the combination of AgNPs and MS-275 is a promising new approach for the
      treatment of lung cancer and our findings contribute to understanding the
      potential roles of AgNPs and MS-275 in pulmonary disease. However, further study
      is warranted to potentiate the use of this combination therapy in cancer therapy
      trials.

PMID- 30111756
TI  - Simple Scores of Fibrosis and Mortality in Patients with NAFLD: A Systematic
      Review with Meta-Analysis.
AB  - Noninvasive simple scores have been validated to assess advanced liver fibrosis
      in patients with nonalcoholic fatty liver disease (NAFLD). We performed a
      systematic review with meta-analysis evaluating if NAFLD fibrosis score (NFS),
      AST to platelet ratio index (APRI), and Fibrosis-4 (FIB-4) score may also predict
      mortality. PubMed and EMBASE databases were searched until April 2018. Random
      effects models were used to calculate pooled RRs of mortality for highest vs.
      lowest categories of exposure and to perform dose-response meta-analysis.
      Heterogeneity was assessed using the Q test and I2 statistic. Overall, eight
      studies were included in the systematic review; all of the eight studies provided
      data for NFS, while four provided data for APRI and FIB-4. When comparing the
      risk estimates for high (>0.676) vs. intermediate + low NFS (<=0.676), we found a
      nearly fourfold increase in mortality risk, with evidence of heterogeneity (RR =
      3.85, 95% CI: 2.08, 7.11; I2 = 92%). At dose-response meta-analysis, compared to
      the midpoint of the lowest category of NFS (-2.5), the risk of mortality was
      about twofold higher for NFS = -0.5 (RR = 2.20, 95% CI: 1.31, 3.70) and more than
      fivefold higher for NFS = 1.5 (RR = 5.16, 95% CI: 2.02, 13.16). When comparing
      the risk estimates for high (>1.5) vs. medium + low APRI (<=1.5), we found a
      higher risk of mortality, without heterogeneity (RR = 3.61, 95% CI: 1.79, 7.28;
      I2 = 0%). Comparison of the risk estimates for high (>2.67) vs. medium + low FIB
      4 (<=2.67) didn't reveal a significantly higher risk of mortality, with
      heterogeneity (RR = 2.27, 95% CI: 0.72, 7.15; I2 = 85%). Dose-response analysis
      for APRI and FIB-4 was not considered conclusive due to the low number of
      studies. Based on the results of our meta-analysis, the measurement of NFS can be
      considered an accurate tool for the stratification of the risk of death in
      patients with NAFLD.

PMID- 30111757
TI  - Fracture Properties and Softening Curves of Steel Fiber-Reinforced Slag-Based
      Geopolymer Mortar and Concrete.
AB  - Adding short steel fibers into slag-based geopolymer mortar and concrete is an
      effective method to enhance their mechanical properties. The fracture properties
      of steel fiber-reinforced slag-based geopolymer concrete/mortar (SGC/SGM) and
      unreinforced control samples were compared through three-point bending (TPB)
      tests. The influences of steel fiber volume contents (1.0%, 1.5% and 2.0%) on the
      fracture properties of SGC and SGM were studied. Load-midspan deflection (P
      delta) curves and load-crack mouth opening displacement (P-CMOD) curves of the
      tested beams were recorded. The compressive and splitting tensile strengths were
      also tested. The fracture energy, flexural strength parameters, and fracture
      toughness of steel fiber-reinforced SGC and SGM were calculated and analyzed. The
      softening curves of steel fiber-reinforced SGC and SGM were determined using
      inverse analysis. The experimental results show that the splitting tensile
      strength, fracture energy, and fracture toughness are significantly enhanced with
      fiber incorporation. A strong correlation between the equivalent and residual
      flexural strengths is also observed. In addition, the trilinear strain-softening
      curves obtained by inverse analysis predict well of the load-displacement curves
      recorded from TPB tests.

PMID- 30111755
TI  - Traditional Uses of Cannabinoids and New Perspectives in the Treatment of
      Multiple Sclerosis.
AB  - Recent findings highlight the emerging role of the endocannabinoid system in the
      control of symptoms and disease progression in multiple sclerosis (MS). MS is a
      chronic, immune-mediated, demyelinating disorder of the central nervous system
      with no cure so far. It is widely reported in the literature that cannabinoids
      might be used to control MS symptoms and that they also might exert
      neuroprotective effects and slow down disease progression. This review aims to
      give an overview of the principal cannabinoids (synthetic and endogenous) used
      for the symptomatic amelioration of MS and their beneficial outcomes, providing
      new potentially possible perspectives for the treatment of this disease.

PMID- 30111758
TI  - Association between the Dietary Inflammatory Index and Risk for Cancer Recurrence
      and Mortality among Patients with Breast Cancer.
AB  - The dietary inflammatory index (DII) has been associated with breast cancer
      incidence and survival. However, the association between DII and cancer
      recurrence and mortality among patients with breast cancer has not been
      investigated. Therefore, the present study aimed to investigate whether DII was
      positively associated with risk for cancer recurrence and overall mortality among
      patients with breast cancer. Among 511 women (51.9 +/- 10.7 years; stage 0-3) who
      underwent breast cancer surgery, 88 had cancer recurrence, and 44 died during
      follow-up until 213 months (average disease free survival of 84.3 +/- 42.4 months
      and overall survival of 69.3 +/- 38.9 months). The DII assessed after surgery
      (5.4 +/- 5.2 months after diagnosis) was significantly higher in patients with
      recurrence than those without recurrence, and Cox proportional hazards regression
      analysis showed that it was positively associated with the risk for cancer
      recurrence (hazard ratio (HR) 2.347, confidence interval (CI) 1.17-4.71) and
      overall mortality (HR 3.049, CI 1.08-8.83) after adjusting for confounding
      factors. Disease-free survival and overall survival rates were significantly
      lower in patients with higher DII scores. In addition, the DII was positively
      associated with the risk for cancer recurrence according to prognostic factors,
      such as age (<50 years), premenopausal status, body mass index (>=25 kg/m2), HR+,
      tumor size (>2 cm), and presence of lymph node metastasis. The present study
      showed that anti-inflammatory diets may decrease the risk of cancer recurrence
      and overall mortality in patients with breast cancer, particularly those with
      prognostic factors, such as younger age, premenopausal status, obesity, HR+
      breast cancer, tumor size >2 cm, and presence of lymph node metastasis.

PMID- 30111759
TI  - Dietary Intake of Vitamin B12 is Better for Restoring a Low B12 Status Than a
      Daily High-Dose Vitamin Pill: An Experimental Study in Rats.
AB  - Vitamin B12 (B12) is present in foods of animal origin, and vegans are encouraged
      to take supplements with synthetic B12 in order to ensure a sufficient uptake.
      Recent rat studies suggest that natural (hydroxo-B12, HO-B12) and synthetic
      (cyano-B12, CN-B12) B12 behave differently in the body. Here, we test if a daily
      vitamin pill matches dietary B12 in ability to restore a low B12 status in rats.
      B12-depleted male Wistar rats (n = 60) were divided into five groups (n = 12 in
      each) and subjected to two weeks intervention with various schemes of B12
      supplementation. Two "dietary" groups received a low-B12 chow that was fortified
      with either HO-B12 or CN-B12 providing a continuous supply. Two "pill" groups
      received a single daily dose of CN-B12, where the vitamin content either matched
      or exceeded by factor four the provisions for the "dietary" groups. A control
      group received the low-B12 chow without B12 fortification. B12 was measured in
      plasma and tissues. Dietary B12 provides 35% more B12 to the tissues than an
      equivalent single daily dose (p < 0.0001). Natural B12 delivers 25% more B12 to
      the liver than synthetic B12 (p = 0.0007). A fourfold increase in B12,
      supplemented as a single daily dose, does not provide any extra B12 to the
      tissues (p = 0.45). We conclude that dietary B12 is better at rescuing a low B12
      status than a daily vitamin pill.

PMID- 30111760
TI  - Effect of Alloying Elements Gradient on Solid-State Diffusion Bonding between
      Aerospace Aluminum Alloys.
AB  - Three different bonding couples assembled by two commonly used aerospace aluminum
      alloys were bonded within the temperature range of 460-520  degrees C under 6 MPa
      for 60 min in vacuum atmosphere. The interface microstructure and alloying
      elements distribution of the bonded joints were determined by scanning electron
      microscope (SEM) and Energy Dispersive Spectroscope (EDS); the bond strength was
      evaluated by tensile-shear strength test. The results show the bond quality
      improved effectively as the bonding temperature increased. Compared with the 1420
      1420 and 7B04-7B04 bonding couples, the 1420-7B04 couples obtained better
      interface integrity and higher bond strength, the highest shear strength for 1420
      7B04 couple can be as high as 188 MPa when bonded at 520  degrees C. Special
      attention was focused on the 1420-7B04 couple, the diffusion coefficient of Mg at
      the original interface under different temperatures were investigated, the
      results show the diffusion coefficient increased obviously as the bonding
      temperature increased. A diffusion affected zone (DAZ) without continuous
      intermetallic phases formed due to the diffusion of alloying elements across the
      bonding interface. The combined action of temperature and alloying elements
      gradient resulted in the increase of alloying elements diffusion fluxes, which in
      turn promote the bonding quality through the accelerated shrinkage of interfacial
      voids.

PMID- 30111761
TI  - The Seasonality of Nitrite Concentrations in a Chloraminated Drinking Water
      Distribution System.
AB  - We studied the seasonal variation of nitrite exposure in a drinking water
      distribution system (DWDS) with monochloramine disinfection in the Helsinki
      Metropolitan Area. In Finland, tap water is the main source of drinking water,
      and thus the nitrite in tap water increases nitrite exposure. Our data included
      both the obligatory monitoring and a sampling campaign data from a sampling
      campaign. Seasonality was evaluated by comparing a nitrite time series to
      temperature and by calculating the seasonal indices of the nitrite time series.
      The main drivers of nitrite seasonality were the temperature and the water age.
      We observed that with low water ages (median: 6.7 h) the highest nitrite exposure
      occurred during the summer months, and with higher water ages (median: 31 h)
      during the winter months. With the highest water age (190 h), nitrite
      concentrations were the lowest. At a low temperature, the high nitrite
      concentrations in the winter were caused by the decelerated ammonium oxidation.
      The dominant reaction at low water ages was ammonium oxidation into nitrite and,
      at high water ages, it was nitrite oxidation into nitrate. These results help to
      direct monitoring appropriately to gain exact knowledge of nitrite exposure.
      Also, possible future process changes and additional disinfection measures can be
      designed appropriately to minimize extra nitrite exposure.

PMID- 30111762
TI  - Protect Your Sleep When Work is Calling: How Work-Related Smartphone Use During
      Non-Work Time and Sleep Quality Impact Next-Day Self-Control Processes at Work.
AB  - In view of the rapid development of information and communication technologies,
      the present study sheds light on how work-related smartphone use during non-work
      time affects employees' subsequent working day. Specifically, we examine work
      related smartphone use and sleep quality as moderators of next-day self-control
      processes at work. Theorizing that work-related smartphone use and self-control
      demands deplete a common limited regulatory resource, we suggest a strengthening
      two-way interaction between work-related smartphone use during non-work time and
      next-day self-control demands at work in predicting employees' ego depletion at
      work. Moreover, in a three-way interaction, we analyze whether this interaction
      depends on employees' sleep quality, assuming that when intensive work-related
      smartphone use is followed by high-quality sleep, the taxed regulatory resource
      can replenish overnight. Results from our diary study covering 10 working days (n
      = 63) indicate that after evenings with high work-related smartphone use,
      employees experience disproportionate levels of ego depletion when dealing with
      self-control demands at work. Sleep quality, however, attenuates this
      interaction. In cases of high sleep quality, next-day self-control processes at
      work are no longer affected by work-related smartphone use. Based on these
      findings, we discuss implications for employees and employers regarding work
      related smartphone use and the relevance of sleep in replenishing drained
      resources.

PMID- 30111763
TI  - Rutacecarpine Inhibits Angiogenesis by Targeting the VEGFR2 and VEGFR2-Mediated
      Akt/mTOR/p70s6k Signaling Pathway.
AB  - This study aimed to investigate the effect of Ru (Rut) on angiogenesis, and the
      underlying regulation mechanism of signal transduction. 3-(4,5-dimethyl-2
      thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, adhesion inhibition
      experiment, migration inhibition experiment, and chick embryo chorioallantoic
      membrane (CAM) assays were performed on models of angiogenesis. The potential
      targets of rutaecarpine (Ru) were reverse screened with Discovery Studio 2017.
      The interaction between the compound and target were detected by surface plasmon
      resonance (SPR), enzyme-activity experiment, and Western blot assay. The obtained
      results confirmed that Ru exhibited modest inhibitory activity against human
      umbilical vein endothelial cells (HUVECs) (IC50 =16.54 +/- 2.4 MUM) and
      remarkable inhibitive effect against the migration and adhesion of HUVECs, as
      well as significant anti-angiogenesis activities in the CAM assay. The possible
      targets of vascular endothelial growth factor receptor 2 (VEGFR2) were identified
      by computer-aided simulation. Results showed a good binding relationship between
      the ligand and target through molecular docking, and this relationship was
      confirmed by SPR analysis. Furthermore, enzyme-activity experiment and western
      blot assay showed that Ru remarkably inhibited the activity of VEGFR2 and blocked
      the VEGFR2-mediated Akt/ (mTOR)/p70s6k signaling pathway in vitro. Ru can be a
      potential drug candidate for cancer prevention and cancer therapy.

PMID- 30111764
TI  - Molecular Characterization and Geographic Distribution of a Mymonavirus in the
      Population of Botrytis cinerea.
AB  - Here, we characterized a negative single-stranded (-ss)RNA mycovirus, Botrytis
      cinerea mymonavirus 1 (BcMyV1), isolated from the phytopathogenic fungus Botrytis
      cinerea. The genome of BcMyV1 is 7863 nt in length, possessing three open reading
      frames (ORF1-3). The ORF1 encodes a large polypeptide containing a conserved
      mononegaviral RNA-dependent RNA polymerase (RdRp) domain showing homology to the
      protein L of mymonaviruses, whereas the possible functions of the remaining two
      ORFs are still unknown. The internal cDNA sequence (10-7829) of BcMyV1 was 97.9%
      identical to the full-length cDNA sequence of Sclerotinia sclerotiorum negative
      stranded RNA virus 7 (SsNSRV7), a virus-like contig obtained from Sclerotinia
      sclerotiorum metatranscriptomes, indicating BcMyV1 should be a strain of SsNSRV7.
      Phylogenetic analysis based on RdRp domains showed that BcMyV1 was clustered with
      the viruses in the family Mymonaviridae, suggesting it is a member of
      Mymonaviridae. BcMyV1 may be widely distributed in regions where B. cinerea
      occurs in China and even over the world, although it infected only 0.8% of tested
      B. cinerea strains.

PMID- 30111765
TI  - A Proof-of-Concept of Label-Free Biosensing System for Food Allergy Diagnostics
      in Biophotonic Sensing Cells: Performance Comparison with ImmunoCAP.
AB  - Food allergy is a common disease worldwide with over 6% of the population (200
      250 million people) suffering from any food allergy nowadays. The most dramatic
      increase seems to be happening in children and young people. Therefore,
      improvements in the diagnosis efficiency of these diseases are needed.
      Immunoglobulin type E (IgE) biomarker determination in human serum is a typical
      in vitro test for allergy identification. In this work, we used a novel biosensor
      based on label-free photonic transducers called BICELLs (Biophotonic Sensing
      Cells) for IgE detection. These BICELLs have a thin film of nitrocellulose over
      the sensing surface, they can be vertical optically interrogated, and are
      suitable for being integrated on a chip. The BICELLs sensing surface sizes used
      were 100 and 800 um in diameter. We obtained calibration curves with IgE
      standards by immobilizating anti-IgE antibodies and identified with standard IgE
      calibrators in minute sample amounts (3 uL). The results, in similar assay
      format, were compared with commercially available ImmunoCAP(r). The versatility
      of the interferometric nitrocellulose-based sensing surface was demonstrated
      since the limit of detections for BICELLs and ImmunoCAP(r) were 0.7 and 0.35
      kU/L, respectively.

PMID- 30111766
TI  - Circular RNA Complement Factor H (CFH) Promotes Glioma Progression by Sponging
      miR-149 and Regulating AKT1.
AB  - BACKGROUND Circular RNAs (circRNAs) are widely expressed in mammals and can
      regulate the development and progression of human tumors. has_circ_0015758 (circ
      CFH) is an exon circRNA transcript from the GRCh37/hg19 fragment of chromosome 1
      and is homologous to the protein-coding gene complement factor H (CFH).
      Currently, the function of circ-CFH in glioma remains unclear. MATERIAL AND
      METHODS In our study, circ-CFH, miR-149, and Akt1 mRNA expression levels were
      analyzed by qRT-PCR assays. To investigate the function of circ-CFH in cell
      proliferation, circ-CFH knockdown models were established by using circ-CFH
      siRNAs. Cell proliferation abilities were measured by CCK-8 and colony formation
      assays and in vivo experiments. In addition, the interaction between circ-CFH and
      miR-149 was assessed by luciferase reporter assays. RESULTS Circ-CFH expression
      was significantly upregulated in glioma tissue and was correlated with tumor
      grade. Circ-CFH expression levels were also markedly higher in U251 and U373
      glioma cell lines. Circ-CFH knockdown inhibited cell proliferation and colony
      formation abilities. Luciferase assays indicated that circ-CFH functions as a miR
      149 sponge and inhibits its function in U251 and U373 cells. Subsequently, AKT1
      was identified as a direct target of the circ-CFH/miR-149 axis. CONCLUSIONS Circ
      CFH promotes glioma progression by sponging miR-149 and regulating the AKT1
      signaling pathway. The circ-CFH/miR-149/AKT1 regulation axis may be a potential
      target for glioma therapy.

PMID- 30111767
TI  - Successful Laparoscopic Cholecystectomy in Moderate to Severe Acute
      Cholecystitis: Visual Explanation with Video File.
AB  - BACKGROUND Experience alone is insufficient to ensure successful laparoscopic
      cholecystectomy (LC), although LC has become widespread worldwide. Iatrogenic
      biliary injuries occur beyond the learning curve. CASE REPORT Biliary injury
      during laparoscopic cholecystectomy results from anatomical misidentification.
      The use of a critical view of safety has been established, to identify the cystic
      artery and the cystic duct, as the cystic duct can be hidden by inflammation
      (infundibular cystic duct). Seven patients who underwent emergency laparoscopic
      cholecystectomy due to acute cholecystitis are presented who underwent a critical
      view of safety protocol during surgery. Five men and two women (mean age, 63.0+/
      13.0 years) included five cases of acute severe cholecystitis and two cases of
      acute moderate cholecystitis. The mean operative time to complete the critical
      view of safety exposure was 54.0+/-17.4 minutes. No cases underwent conversion to
      open surgery. The mean postoperative duration to ambulation and normal diet was
      0.7+/-0.5 days and 1.0+/-0.6 days, respectively. The mean time to postoperative
      patient discharge was 3.9+/-0.9 days. In all seven cases, the postoperative
      course was uneventful. The protocol for this surgical procedure is presented,
      with schematic figures and videos. CONCLUSIONS A case series of seven patients
      who presented with moderate-to-severe acute cholecystitis and who underwent
      laparoscopic cholecystectomy, showed good postoperative outcome without surgical
      complications, using a using a critical view of safety protocol.

PMID- 30111769
TI  - DNMT1 and DNMT3A haplotypes associated with noise-induced hearing loss in Chinese
      workers.
AB  - This study was conducted to explore the effects of DNMT1 and DNMT3A polymorphisms
      on susceptibility to noise-induced hearing loss (NIHL) in Chinese workers. A
      total of 2689 industrial workers from a single textile factory were recruited.
      Venous blood was collected, as were questionnaire and pure-tone audiometry (PTA)
      data by specialist physicians. Four selected SNPs (rs7578575, rs749131,
      rs1550117, and rs2228611) in DNMT1 and DNMT3A were genotyped in 527 NIHL patients
      and 527 controls. Then, main effects of the genotypes and their interactions were
      evaluated. Results revealed that the GG genotype at rs749131 and the AG/GG
      genotypes at rs1550117 and rs2228611 [odds ratio (OR) = 1.87, 2.57, and 1.98
      respectively], as well as the haplotypes AGGG and TGGA (rs7578578-rs749131
      rs1550117-rs2228611) (OR = 1.35 and 1.56, respectively) were associated with an
      increased risk of NIHL in the Chinese population. Multifactor dimensionality
      reduction analysis indicated that rs7578575, rs749131, and rs2228611 interact and
      are related to increased NIHL risk (OR = 1.63). The genetic polymorphisms
      rs749131 G, rs1550117 G, and rs2228611 G within the DNMT1 and DNMT3A genes are
      associated with an increased risk of NIHL in the Chinese population and have the
      potential to act as biomarkers for noise-exposed workers.

PMID- 30111768
TI  - Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and
      pathways for cardiovascular disease.
AB  - Identifying genetic variants associated with circulating protein concentrations
      (protein quantitative trait loci; pQTLs) and integrating them with variants from
      genome-wide association studies (GWAS) may illuminate the proteome's causal role
      in disease and bridge a knowledge gap regarding SNP-disease associations. We
      provide the results of GWAS of 71 high-value cardiovascular disease proteins in
      6861 Framingham Heart Study participants and independent external replication. We
      report the mapping of over 16,000 pQTL variants and their functional relevance.
      We provide an integrated plasma protein-QTL database. Thirteen proteins harbor
      pQTL variants that match coronary disease-risk variants from GWAS or test causal
      for coronary disease by Mendelian randomization. Eight of these proteins predict
      new-onset cardiovascular disease events in Framingham participants. We
      demonstrate that identifying pQTLs, integrating them with GWAS results, employing
      Mendelian randomization, and prospectively testing protein-trait associations
      holds potential for elucidating causal genes, proteins, and pathways for
      cardiovascular disease and may identify targets for its prevention and treatment.

PMID- 30111771
TI  - Experimental investigations on drag-reduction characteristics of bionic surface
      with water-trapping microstructures of fish scales.
AB  - Biological surfaces with unique wettability in nature have provided an enormous
      innovation for scientists and engineers. More specifically, materials possessing
      various wetting properties have drawn considerable attention owing to their
      promising application prospects. Recently, great efforts have been concentrated
      on the researches on wetting-induced drag-reduction materials inspired by biology
      because of their ability to save energy. In this work, the drag-reduction
      characteristics of the bionic surface with delicate water-trapping
      microstructures of fish Ctenopharyngodon idellus scales were explored by
      experimental method. Firstly, the resistance of smooth surface and bionic surface
      experimental sample at different speeds was carefully tested through the testing
      system for operation resistance. Then, the contact angle (CA) of fish scale
      surface was measured by means of the contact angle measuring instrument. It was
      discovered that the bionic surface created a rewarding drag-reduction effect at a
      low speed, and the drag-reduction rate significantly displayed a downward trend
      with the increase in flow speed. Thus, when the rate was 0.66 m/s, the drag
      reduction effect was at the optimum level, and the maximum drag reduction rate
      was 2.805%, which was in concordance with the simulated one. Furthermore, a
      contact angle (CA) of 11.5 degrees  appeared on the fish scale surface,
      exhibiting fine hydrophilic property. It further manifested the spreading-wetting
      phenomenon and the higher surface energy for the area of apical of fish scales,
      which played an important role in drag-reduction performance. This work will have
      a great potential in the engineering and transportation field.

PMID- 30111770
TI  - Cholestasis induced liver pathology results in dysfunctional immune responses
      after arenavirus infection.
AB  - Immune responses are critical for defense against pathogens. However, prolonged
      viral infection can result in defective T cell immunity, leading to chronic viral
      infection. We studied immune activation in response to arenavirus infection
      during cholestasis using bile duct ligation (BDL). We monitored T cell responses,
      virus load and liver pathology markers after infection with lymphocytic
      choriomeningitis virus (LCMV). BDL mice failed to induce protective anti-viral
      immunity against LCMV and consequently exhibited chronic viral infection. BDL
      mice exhibited reduced anti-viral T cell immunity as well as reduced type 1
      interferon production early after LCMV infection. Consistently, the presence of
      serum from BDL mice reduced the responsiveness of dendritic cell (DC) and T cell
      cultures when compared to Sham controls. Following fractionation and mass
      spectrometry analyses of sera, we identified several serum factors to be
      upregulated following BDL including bilirubin, bile acids, 78 kDa Glucose
      regulated protein (GRP78) and liver enzymes. Bilirubin and GRP78 were capable of
      inhibiting DC and T cell activation. In this work, we demonstrate that liver
      damage mediated by cholestasis results in defective immune induction following
      arenavirus infection.

PMID- 30111772
TI  - Large-Scale Encapsulation of Magnetic Iron Oxide Nanoparticles via Syngas Photo
      Initiated Chemical Vapor Deposition.
AB  - Photo-initiated chemical vapor deposition (PICVD) has been adapted for use in a
      jet-assisted fluidized bed configuration, allowing for the encapsulation of
      magnetic iron oxide nanoparticles on a larger scale than ever reported (5 g).
      This new methodology leads to a functional coating with a thickness of 1.4-10 nm,
      confirmed by HRTEM and TGA. XPS and TOF-SIMS characterization confirm that the
      coating is composed of both aliphatic and polymerized carbon chains, with
      incorporated organometallic bonds and oxygen-containing moieties. UV-Vis
      absorbance spectra show that the coating improved dispersion in non-polar
      solvents, such as n-dodecane. This process represents a first step towards the
      large-scale, solvent-free post-synthesis processing of nanoparticles to impart a
      functional coating.

PMID- 30111773
TI  - Genetic relatedness of Staphylococcus aureus isolates obtained from cystic
      fibrosis patients at a tertiary academic hospital in Pretoria, South Africa.
AB  - Cystic fibrosis (CF) is an inherited recessive disease that affects mucocillary
      clearance in the lung, allowing it to be colonised with bacteria such as
      Staphylococcus aureus. To survive in the CF lung S. aureus adapts both
      phenotypically and genotypically, through various mechanisms. In this study,
      multiple specimens were collected from the participants and were processed
      routinely and were additionally cultured in chromogenic media. Multiplex PCR
      assays were employed to detect methicillin resistance and selected virulence and
      quaternary ammonium compound (qac) genes. Genetic relatedness of the S. aureus
      was determined using agr, SCCmec and spa typing as well as pulsed field gel
      electrophoresis (PFGE) and multi-locus sequence typing (MLST). Thirty-three S.
      aureus isolates were isolated, of which 51% (17/33) were methicillin resistant S.
      aureus (MRSA). The virulence and qac genes were more prevalent in MRSA than the
      methicillin sensitive S. aureus (MSSA) isolates. The PFGE analysis showed nine
      distinct pulsotypes while MLST showed eight sequence types. All the STs detected
      in this study, except for ST508 have been previously isolated from CF patients
      according to the literature. This study showed a genetically diverse S. aureus
      population with a high prevalence of virulence genes among the MRSA isolates from
      the CF clinic.

PMID- 30111776
TI  - Auditory advances.

PMID- 30111775
TI  - Structure Properties of Generalized Farey graphs based on Dynamical Systems for
      Networks.
AB  - Farey graphs are simultaneously small-world, uniquely Hamiltonian, minimally 3
      colorable, maximally outerplanar and perfect. Farey graphs are therefore famous
      in deterministic models for complex networks. By lacking of the most important
      characteristics of scale-free, Farey graphs are not a good model for networks
      associated with some empirical complex systems. We discuss here a category of
      graphs which are extension of the well-known Farey graphs. These new models are
      named generalized Farey graphs here. We focus on the analysis of the topological
      characteristics of the new models and deduce the complicated and graceful
      analytical results from the growth mechanism used in generalized Farey graphs.
      The conclusions show that the new models not only possess the properties of being
      small-world and highly clustered, but also possess the quality of being scale
      free. We also find that it is precisely because of the exponential increase of
      nodes' degrees in generalized Farey graphs as they grow that caused the new
      networks to have scale-free characteristics. In contrast, the linear
      incrementation of nodes' degrees in Farey graphs can only cause an exponential
      degree distribution.

PMID- 30111774
TI  - Novel monoclonal antibody L2A5 specifically targeting sialyl-Tn and short glycans
      terminated by alpha-2-6 sialic acids.
AB  - Incomplete O-glycosylation is a feature associated with malignancy resulting in
      the expression of truncated glycans such as the sialyl-Tn (STn) antigen. Despite
      all the progress in the development of potential anti-cancer antibodies, their
      application is frequently hindered by low specificities and cross-reactivity. In
      this study, a novel anti-STn monoclonal antibody named L2A5 was developed by
      hybridoma technology. Flow cytometry analysis showed that L2A5 specifically binds
      to sialylated structures on the cell surface of STn-expressing breast and bladder
      cancer cell lines. Moreover, immunoblotting assays demonstrated reactivity to
      tumour-associated O-glycosylated proteins, such as MUC1. Tumour recognition was
      further observed using immunohistochemistry assays, which demonstrated a high
      sensitivity and specificity of L2A5 mAb towards cancer tissue, using bladder and
      colorectal cancer tissues. L2A5 staining was exclusively tumoural, with a
      remarkable reactivity in invasive and metastasis sites, not detectable by other
      anti-STn mAbs. Additionally, it stained 20% of cases of triple-negative breast
      cancers, suggesting application in diseases with unmet clinical needs. Finally,
      the fine specificity was assessed using glycan microarrays, demonstrating a
      highly specific binding of L2A5 to core STn antigens and additional ability to
      bind 2-6-linked sialyl core-1 probes. In conclusion, this study describes a novel
      anti-STn antibody with a unique binding specificity that can be applied for
      cancer diagnostic and future development of new antibody-based therapeutic
      applications.

PMID- 30111777
TI  - A moldable sustained release bupivacaine formulation for tailored treatment of
      postoperative dental pain.
AB  - A moldable and biodegradable dental material was designed for customized
      placement and sustained delivery of bupivacaine (BP) within an extraction cavity.
      Microparticles comprising poly(lactic-co-glycolic acid) (PLGA) containing BP were
      generated via solvent-evaporation and combined with absorbable hemostat
      Gelfoam(r). Kinetics of drug release were evaluated by in vitro dialysis assays,
      showing higher release within the first 24 hours, with subsequent tapering of
      release kinetics. Formulations of Gelfoam(r) and BP-PLGA microparticles (GelBP),
      with three targeted dosing profiles (0.25, 0.5, and 1 mg/kg/day), were evaluated
      alongside acute subcutaneous BP injections (2 mg/kg) to determine analgesic
      efficacy in a rat model of tooth extraction pain. Molar extraction resulted in
      mechanical and thermal cold hyperalgesia in male and female rats. GelBP
      outperformed acute BP in blocking post-surgical dental pain, with the 0.25 mg/kg
      GelBP dose preventing hypersensitivity to mechanical (p < 0.01) and thermal cold
      stimuli (p = 0.05). Molar extraction also resulted in decreased food consumption
      and weight. Males receiving acute BP and 0.25 mg/kg GelBP maintained normal food
      consumption (p < 0.002) and weight (p < 0.0001) throughout 7 days. Females,
      receiving 0.25 mg/kg GelBP maintained weight on days 5-7 (p < 0.04). Customized,
      sustained release formulation of anesthetic within a tooth extraction cavity
      holds potential to eliminate post-operative dental pain over several days.

PMID- 30111778
TI  - Exploring scenarios of chikungunya mitigation with a data-driven agent-based
      model of the 2014-2016 outbreak in Colombia.
AB  - New epidemics of infectious diseases can emerge any time, as illustrated by the
      emergence of chikungunya virus (CHIKV) and Zika virus (ZIKV) in Latin America.
      During new epidemics, public health officials face difficult decisions regarding
      spatial targeting of interventions to optimally allocate limited resources. We
      used a large-scale, data-driven, agent-based simulation model (ABM) to explore
      CHIKV mitigation strategies, including strategies based on previous DENV
      outbreaks. Our model represents CHIKV transmission in a realistic population of
      Colombia with 45 million individuals in 10.6 million households, schools, and
      workplaces. Our model uses high-resolution probability maps for the occurrence of
      the Ae. aegypti mosquito vector to estimate mosquito density in Colombia. We
      found that vector control in all 521 municipalities with mosquito populations led
      to 402,940 fewer clinical cases of CHIKV compared to a baseline scenario without
      intervention. We also explored using data about previous dengue virus (DENV)
      epidemics to inform CHIKV mitigation strategies. Compared to the baseline
      scenario, 314,437 fewer cases occurred when we simulated vector control only in
      301 municipalities that had previously reported DENV, illustrating the value of
      available data from previous outbreaks. When varying the implementation
      parameters for vector control, we found that faster implementation and scale-up
      of vector control led to the greatest proportionate reduction in cases. Using
      available data for epidemic simulations can strengthen decision making against
      new epidemic threats.

PMID- 30111780
TI  - Metal concentrations in pregnant women and neonates from informal electronic
      waste recycling.
AB  - Electronic waste (e-waste) is the fastest growing solid waste stream worldwide
      and mostly ends up in developing countries where residents use primitive methods
      for recycling. The most infamous e-waste recycling town, Guiyu in Southeast
      China, has been recycling since the mid-1990s. E-waste contains several harmful
      chemicals, including lead (Pb), cadmium (Cd), chromium (Cr), and manganese (Mn).
      In 2011-12, the e-waste Recycling Exposures and Community Health (e-REACH) Study
      enrolled 634 pregnant women living in Guiyu and Haojiang, a control site, both in
      Shantou, China. The women completed a questionnaire and gave maternal blood, cord
      blood, and maternal urine, which were analyzed for Pb, Cd, Cr, and Mn. Maternal
      blood Pb, Cd, and Cr concentrations were significantly higher in Guiyu compared
      to Haojiang. In Guiyu, the geometric mean of Pb concentration in maternal blood
      was 6.66 ug/dL (range: 1.87-27.09 ug/dL) and was 1.74-fold greater than in
      Haojiang (95% CI: 1.60, 1.89). In cord blood, Pb concentration was 1.53-fold
      higher in Guiyu (95% CI: 1.38, 1.68). In maternal urine, Cd (ratio: 2.15, 95% CI:
      1.72, 2.69) and Mn (ratio: 2.60, 95% CI: 2.04, 3.31) concentrations were
      significantly higher in Guiyu in comparison to Haojiang. In conclusion, pregnant
      women in Guiyu were at risk for increased exposure to heavy metals.

PMID- 30111779
TI  - Human tissue-engineered skeletal muscle: a novel 3D in vitro model for drug
      disposition and toxicity after intramuscular injection.
AB  - The development of laboratory-grown tissues, referred to as organoids, bio
      artificial tissue or tissue-engineered constructs, is clearly expanding. We
      describe for the first time how engineered human muscles can be applied as a pre-
      or non-clinical model for intramuscular drug injection to further decrease and
      complement the use of in vivo animal studies. The human bio-artificial muscle
      (BAM) is formed in a seven day tissue engineering procedure during which human
      myoblasts fuse and differentiate to aligned myofibers in an extracellular matrix.
      The dimensions of the BAM constructs allow for injection and follow-up during
      several days after injection. A stereotactic setup allows controllable injection
      at multiple sites in the BAM. We injected several compounds; a dye, a
      hydrolysable compound, a reducible substrate and a wasp venom toxin. Afterwards,
      direct reflux, release and metabolism were assessed in the BAM constructs in
      comparison to 2D cell culture and isolated human muscle strips. Spectrophotometry
      and luminescence allowed to measure the release of the injected compounds and
      their metabolites over time. A release profile over 40 hours was observed in the
      BAM model in contrast to 2D cell culture, showing the capacity of the BAM model
      to function as a drug depot. We also determined compound toxicity on the BAMs by
      measuring creatine kinase release in the medium, which increased with increasing
      toxic insult. Taken together, we show that the BAM is an injectable human 3D cell
      culture model that can be used to measure release and metabolism of injected
      compounds in vitro.

PMID- 30111781
TI  - Curve-fitting techniques improve the mid-infrared analysis of soil organic
      carbon: a case study for Brookston clay loam particle-size fractions.
AB  - Few studies have evaluated structural features of soil organic carbon (SOC) in
      different soil particle fractions, especially SOC changes induced by tillage,
      using Fourier transformed mid-infrared (MIR) spectroscopy. To make a contribution
      in this context, soil samples of a Brookston clay loam (mesic Typic Argiaquoll)
      with averaged pH and organic matter concentration at 7.28 and 43.9 g kg-1,
      respectively, were collected from short-term no-tillage (NT97) and mouldboard
      plow (CT97) treatments initiated in 1997 and long-term no-tillage (NT83) and
      mouldboard plow (CT83) treatments initiated in 1983 under a corn-soybean
      rotation, and were separated into sand, silt, and clay fractions using
      sonication. Structural features of SOC in these soil fractions were investigated
      using curve-fitting analysis of mid-infrared (MIR) spectra. Aromatic C content
      was found to be greater in clay- than in sand-sized fractions, while aliphatic C
      content was higher in sand- than in silt- and clay-sized particles. With decrease
      in tillage intensity, the aliphatic C gradually increased in sand- and clay-sized
      fractions but not in the silt-sized fraction. The aliphatic C content in sand
      fraction was significantly greater in NT83 than CT83 (P < 0.05). The aromatic C
      in silt- and clay-sized fractions was greater in NT83 than in both CT soils,
      whereas aromatic C contents were higher in both CT soils than in NT83 soil.
      Significantly higher aromatic/aliphatic C ratio in CT83 than NT83 was found in
      sand-sized fractions, while the opposite trend was found in the silt-sized
      fraction. These findings were not apparent until the curve-fitting technique was
      employed, which has the capacity to quantify many overlapped bands in the
      spectra. This study demonstrates that the curve-fitting of MIR spectra advances
      the analysis of organic matter in soil samples.

PMID- 30111782
TI  - Heavy metals in Yinma River sediment in a major Phaeozems zone, Northeast China:
      Distribution, chemical fraction, contamination assessment and source
      apportionment.
AB  - Yinma River is a typical river in the major Phaeozems zone of Northeast China. It
      has been suffering an increasing environmental pressure from heavy metal
      contamination due to the rapid development of population, social-economy and
      urbanization as well as long term over cultivation. This study investigated the
      spatial distribution, chemical fraction of heavy metals (Cu, Pb, Zn, Cr, Cd, Ni,
      As, and Hg) in sediments of Yinma River based on BCR procedure, assessed the
      contamination level, and identified their sources via multivariate statistical
      analysis. The chemical fraction results indicated that Cd, Pb, Ni, and Zn
      exhibited higher mobility susceptibility and bioavailability with a significant
      and late anthropogenic origin. Hg and Cd might exert a potential hazardous
      influence on aquatic biota according to the geo-accumulation index (Igeo). The
      pollution load index (PLI) assessment suggested that all of the sediment samples
      have been contaminated. Multivariate statistical analysis revealed that Zn, Cu,
      Hg, Cd, and Pb reflected the anthropogenic sources with a close correlation with
      TOC and socio-economic development; Ni, As and Cr tended to represent the
      geochemical background. Furthermore, Changchun City and Shitoukoumen Reservoir as
      the major drinking water source may be hotspots of the heavy metal contamination
      in the watershed.

PMID- 30111783
TI  - Novel Hybrid Energy Conversion and Storage Cell with Photovoltaic and
      Supercapacitor Effects in Ionic Liquid Electrolyte.
AB  - A single hybrid energy conversion and storage (HECS) cell of alpha-cobalt
      hydroxide (alpha-Co(OH)2) in ionic liquid was fabricated and operated under light
      illumination. The alpha-Co(OH)2, which is unstable in an aqueous electrolyte
      (i.e. KOH), is surprisingly stable in 1-butyl-1-methyl-pyrrolidinium dicyanamide
      ionic liquid. The as-fabricated HECS cell provides 100% coulombic efficiency and
      99.99% capacity retention over 2000 cycles. Under a photo-charging condition, the
      dicyanamide anion of ionic liquid can react with a generated alpha-Co(OH)2+ hole
      at the positive electrode since the HOMO energy level of the anion is close to
      the valence band of alpha-Co(OH)2. The excited photoelectron will transfer to the
      current collector and move to the negative electrode. At the negative electrode,
      the 1-butyl-1-methyl-pyrrolidinium cations of ionic liquid do electrostatically
      adsorb on the surface and intercalate into the interlayer of active material
      stabilizing the whole cell. The HECS cell having both energy conversion
      (photovoltaic effect) and energy storage (supercapacitor) properties may be an
      ideal device for future renewable energy.

PMID- 30111784
TI  - The Hippo pathway in the heart: pivotal roles in development, disease, and
      regeneration.
AB  - The Hippo-YAP (Yes-associated protein) pathway is an evolutionarily and
      functionally conserved regulator of organ size and growth with crucial roles in
      cell proliferation, apoptosis, and differentiation. This pathway has great
      potential for therapeutic manipulation in different disease states and to promote
      organ regeneration. In this Review, we summarize findings from the past decade
      revealing the function and regulation of the Hippo-YAP pathway in cardiac
      development, growth, homeostasis, disease, and regeneration. In particular, we
      highlight the roles of the Hippo-YAP pathway in endogenous heart muscle renewal,
      including the pivotal role of the Hippo-YAP pathway in regulating cardiomyocyte
      proliferation and differentiation, stress response, and mechanical signalling.
      The human heart lacks the capacity to self-repair; therefore, the loss of
      cardiomyocytes after injury such as myocardial infarction can result in heart
      failure and death. Despite substantial advances in the treatment of heart
      failure, an enormous unmet clinical need exists for alternative treatment
      options. Targeting the Hippo-YAP pathway has tremendous potential for developing
      therapeutic strategies for cardiac repair and regeneration for currently
      intractable cardiovascular diseases such as heart failure. The lessons learned
      from cardiac repair and regeneration studies will also bring new insights into
      the regeneration of other tissues with limited regenerative capacity.

PMID- 30111785
TI  - Trends of Visual Impairment and Blindness in the Singapore Chinese Population
      over a Decade.
AB  - We evaluated the prevalence of visual impairment (VI) and blindness among Chinese
      adults in the Singapore Chinese Eye Study (SCES, 2009-2011), and compared the
      trends with the Tanjong Pagar Survey, Singapore (TPS), conducted a decade
      earlier. The SCES comprised of 3,353 Chinese adults aged >=40 years (response
      rate, 72.8%). Participants underwent standardized examinations, including
      measurements of presenting, and best-corrected visual acuity (VA). Bilateral VI
      (VA < 20/40 to >=20/200) and blindness (VA < 20/200) were defined based on the
      United States definition (better-seeing eye). Age-standardized prevalence was
      calculated using the 2010 Singapore Chinese Population Census. Primary causes and
      factors associated with VI and blindness were evaluated. In SCES, the age
      standardized prevalence of presenting bilateral VI and blindness were 17.7% and
      0.6%, respectively; the age-standardised prevalence of best-corrected bilateral
      VI and blindness were 3.4% and 0.2%, respectively. The previous TPS reported
      similar rates of best-corrected bilateral VI (3.8%) and blindness (0.3%). In
      SCES, cataract remains the main cause for both best-corrected bilateral VI
      (76.0%) and blindness (50.0%). Older age, female, lower income, lower educational
      level, and smaller housing type were associated with presenting bilateral VI or
      blindness (all P <= 0.025). These findings will be useful for the planning of eye
      care services and resource allocation.

PMID- 30111786
TI  - Isolation and characterization of nanometre aggregates from a Bai-Hu-Tang
      decoction and their antipyretic effect.
AB  - In China, a decoction is one of the most common clinical dosage forms. Nanometre
      aggregates (NAs), which often consist of circular or irregular nanoparticles,
      have been observed in previous research on decoctions. A Bai-Hu-Tang (BHT)
      decoction is an ancient clinical dosage form in China. The purpose of this work
      was to isolate and characterize NAs from BHT and to investigate their antipyretic
      effect. A BHT decoction was prepared by the traditional method. The mechanism and
      active components of the aggregates in BHT were investigated by high-speed
      centrifugation, transmission electron microscopy (TEM), and HPLC (high
      performance liquid chromatography). In addition to the aggregation, therapeutic
      activities were evaluated through temperature measurements, enzyme-linked
      immunosorbent assays, cellular uptake measurements and fluorescence imaging. The
      majority of the NAs in BHT had diameters of 100 nm, and the spherical structures
      contained C, O, Mg, Al, Si, Ca, Zn et al. Antipyretic bioactive compounds, such
      as neomangiferin, mangiferin, glycyrrhizic acid and ammonium glycyrrhizinate,
      existed in the aggregates. In addition, the NAs in BHT had a better antipyretic
      effect than the other dispersion phases of BHT. In particular, the nanometre
      aggregates of Bai-Hu-Tang (N-BHT) were easily taken up by cells, and the
      fluorescein isothiocyanate (FITC) signals of NAs were more enriched in the lungs
      and brain than in other organs over time. These results revealed that the
      antipyretic effect was associated with the NAs in BHT. The discovery of NAs might
      present a new perspective for understanding BHT decoctions and even lead to the
      development of a new nanomedicine approach in traditional Chinese medicine
      (TCMs). Therefore, this topic deserves further study.

PMID- 30111788
TI  - Marine heatwaves under global warming.
AB  - Marine heatwaves (MHWs) are periods of extreme warm sea surface temperature that
      persist for days to months1 and can extend up to thousands of kilometres2. Some
      of the recently observed marine heatwaves revealed the high vulnerability of
      marine ecosystems3-11 and fisheries12-14 to such extreme climate events. Yet our
      knowledge about past occurrences15 and the future progression of MHWs is very
      limited. Here we use satellite observations and a suite of Earth system model
      simulations to show that MHWs have already become longer-lasting and more
      frequent, extensive and intense in the past few decades, and that this trend will
      accelerate under further global warming. Between 1982 and 2016, we detect a
      doubling in the number of MHW days, and this number is projected to further
      increase on average by a factor of 16 for global warming of 1.5 degrees Celsius
      relative to preindustrial levels and by a factor of 23 for global warming of 2.0
      degrees Celsius. However, current national policies for the reduction of global
      carbon emissions are predicted to result in global warming of about 3.5 degrees
      Celsius by the end of the twenty-first century16, for which models project an
      average increase in the probability of MHWs by a factor of 41. At this level of
      warming, MHWs have an average spatial extent that is 21 times bigger than in
      preindustrial times, last on average 112 days and reach maximum sea surface
      temperature anomaly intensities of 2.5 degrees Celsius. The largest changes are
      projected to occur in the western tropical Pacific and Arctic oceans. Today, 87
      per cent of MHWs are attributable to human-induced warming, with this ratio
      increasing to nearly 100 per cent under any global warming scenario exceeding 2
      degrees Celsius. Our results suggest that MHWs will become very frequent and
      extreme under global warming, probably pushing marine organisms and ecosystems to
      the limits of their resilience and even beyond, which could cause irreversible
      changes.

PMID- 30111787
TI  - Meeting report: a close look at oral biofilms and microbiomes.
AB  - The "Biofilms, Microbiomes and Oral Diseases: Challenges and Future Perspectives"
      symposium jointly organized by Penn Dental Medicine and West China School of
      Stomatology was held on 30 September 2017 at Penn Wharton China Center (PWCC) in
      Beijing, China. The topics included the pathogenicity of oral biofilms, novel
      strategies for the control of biofilm-related diseases, oral microbiome and
      single-cell approaches, and the link between oral diseases and overall health.
      Researchers from a number of disciplines, representing institutions from China
      and Penn Dental Medicine, gathered to discuss advances in our understanding of
      biofilms, as well as future directions for the control of biofilm-related oral
      and systemic diseases.

PMID- 30111789
TI  - Cryo-STEM mapping of solid-liquid interfaces and dendrites in lithium-metal
      batteries.
AB  - Solid-liquid interfaces are important in a range of chemical, physical and
      biological processes1-4, but are often not fully understood owing to the lack of
      high-resolution characterization methods that are compatible with both solid and
      liquid components5. For example, the related processes of dendritic deposition of
      lithium metal and the formation of solid-electrolyte interphase layers6,7 are
      known to be key determinants of battery safety and performance in high-energy
      density lithium-metal batteries. But exactly what is involved in these two
      processes, which occur at a solid-liquid interface, has long been debated8-11
      because of the challenges of observing such interfaces directly. Here we adapt a
      technique that has enabled cryo-transmission electron microscopy (cryo-TEM) of
      hydrated specimens in biology-immobilization of liquids by rapid freezing, that
      is, vitrification12. By vitrifying the liquid electrolyte we preserve it and the
      structures at solid-liquid interfaces in lithium-metal batteries in their native
      state, and thus enable structural and chemical mapping of these interfaces by
      cryo-scanning transmission electron microscopy (cryo-STEM). We identify two
      dendrite types coexisting on the lithium anode, each with distinct structure and
      composition. One family of dendrites has an extended solid-electrolyte interphase
      layer, whereas the other unexpectedly consists of lithium hydride instead of
      lithium metal and may contribute disproportionately to loss of battery capacity.
      The insights into the formation of lithium dendrites that our work provides
      demonstrate the potential of cryogenic electron microscopy for probing nanoscale
      processes at intact solid-liquid interfaces in functional devices such as
      rechargeable batteries.

PMID- 30111790
TI  - Cooperative asymmetric reactions combining photocatalysis and enzymatic
      catalysis.
AB  - Living organisms rely on simultaneous reactions catalysed by mutually compatible
      and selective enzymes to synthesize complex natural products and other
      metabolites. To combine the advantages of these biological systems with the
      reactivity of artificial chemical catalysts, chemists have devised sequential,
      concurrent, and cooperative chemoenzymatic reactions that combine enzymatic and
      artificial catalysts1-9. Cooperative chemoenzymatic reactions consist of
      interconnected processes that generate products in yields and selectivities that
      cannot be obtained when the two reactions are carried out sequentially with their
      respective substrates2,7. However, such reactions are difficult to develop
      because chemical and enzymatic catalysts generally operate in different media at
      different temperatures and can deactivate each other1-9. Owing to these
      constraints, the vast majority of cooperative chemoenzymatic processes that have
      been reported over the past 30 years can be divided into just two categories:
      chemoenzymatic dynamic kinetic resolutions of racemic alcohols and amines, and
      enzymatic reactions requiring the simultaneous regeneration of a cofactor2,4,5.
      New approaches to the development of chemoenzymatic reactions are needed to
      enable valuable chemical transformations beyond this scope. Here we report a
      class of cooperative chemoenzymatic reaction that combines photocatalysts that
      isomerize alkenes with ene-reductases that reduce carbon-carbon double bonds to
      generate valuable enantioenriched products. This method enables the
      stereoconvergent reduction of E/Z mixtures of alkenes or reduction of the
      unreactive stereoisomers of alkenes in yields and enantiomeric excesses that
      match those obtained from the reduction of the pure, more reactive isomers. The
      system affords a range of enantioenriched precursors to biologically active
      compounds. More generally, these results show that the compatibility between
      photocatalysts and enzymes enables chemoenzymatic processes beyond cofactor
      regeneration and provides a general strategy for converting stereoselective
      enzymatic reactions into stereoconvergent ones.

PMID- 30111791
TI  - The preprint.

PMID- 30111792
TI  - Plagiarism rules, discrimination settlements and asteroid close-up.

PMID- 30111793
TI  - How Unpaywall is transforming open science.

PMID- 30111794
TI  - Ohmic transition at contacts key to maximizing fill factor and performance of
      organic solar cells.
AB  - While thermodynamic detailed balance limits the maximum power conversion
      efficiency of a solar cell, the quality of its contacts can further limit the
      actual efficiency. The criteria for good contacts to organic semiconductors,
      however, are not well understood. Here, by tuning the work function of poly(3,4
      ethylenedioxythiophene) hole collection layers in fine steps across the Fermi
      level pinning threshold of the model photoactive layer, poly(3
      hexylthiophene):phenyl-C61-butyrate methyl ester, in organic solar cells, we
      obtain direct evidence for a non-ohmic to ohmic transition at the hole contact
      that lies 0.3 eV beyond its Fermi-level pinning transition. This second
      transition corresponds to reduction of the photocurrent extraction resistance
      below the bulk resistance of the cell. Current detailed balance analysis reveals
      that this extraction resistance is the counterpart of injection resistance, and
      the measured characteristics are manifestations of charge carrier hopping across
      the interface. Achieving ohmic transition at both contacts is key to maximizing
      fill factor without compromising open-circuit voltage nor short-circuit current
      of the solar cell.

PMID- 30111795
TI  - In vitro and in vivo evaluation of the genotoxic and antigenotoxic potential of
      the major Chios mastic water constituents.
AB  - Chios mastic products are well-known for their broad applications in food
      industry, cosmetics, and healthcare since the antiquity. Given our recent finding
      that Chios mastic water (CMW) exerts antigenotoxic action, in the present study,
      we evaluated the genotoxic as well as the antigenotoxic potential of the four
      major compounds of CMW, namely, verbenone, alpha-terpineol, linalool, and trans
      pinocarveol. The cytokinesis block micronucleus (CBMN) assay in cultured human
      lymphocytes and the Drosophila Somatic Mutation And Recombination Test (SMART),
      also known as the wing spot test, were employed. None of the four major CMW's
      constituents or their mixtures showed genotoxic or recombinogenic activity in
      either of the assays used. Co-treatment of each of the constituents with MMC
      revealed that all except trans-pinocarveol exerted antigenotoxic potential.
      Moreover, co-administration of verbenone with linalool or alpha-terpineol
      presented statistically significant reduction of MMC-induced mutagenicity. In
      conclusion, the major CMW constituents were shown to be free of genotoxic
      effects, while some exerted antigenotoxic activity either alone or in
      combinations, suggesting synergistic phenomena. Our results provide evidence on
      the key antigenotoxicity effectors of the plant extract CMW.

PMID- 30111796
TI  - Changes in Antimicrobial Usage Patterns in Korea: 12-Year Analysis Based on
      Database of the National Health Insurance Service-National Sample Cohort.
AB  - National antimicrobial usage and prescription patterns during the 12 years from
      2002 to 2013 were analyzed using the National Health Insurance Service-National
      Sample Cohort. Antimicrobial usage was analyzed by major illness, sex, age, area
      of residence, income rank, diagnosis, and type of medical institution for each
      year. Total antimicrobial prescriptions increased from 15.943 daily defined dose
      (DDD)/1,000 inhabitants/day in 2002 to 24.219 in 2013. In 2013, 72% of total
      prescriptions were administered in clinics. Antimicrobials were most frequently
      prescribed to children younger than 10 years, followed by adults aged 70 years or
      older and those aged 60-69 years. Penicillins and cephems were the most popular
      classes of antimicrobial used. In 2013, 48% of total antibiotic usage (11.683
      DDD/1,000 inhabitants/day) was due to respiratory diseases. After the Korean
      government has implemented a series of healthcare policies, antibiotic
      prescription decreased for the treatment of upper respiratory infection, the
      causative agents are mostly viruses.

PMID- 30111797
TI  - Wnt pathway is involved in 5-FU drug resistance of colorectal cancer cells.
AB  - Colorectal cancer (CRC) is one of the leading causes of cancer-related death
      worldwide. 5-Fluorouracil (5-FU) is widely used in the treatment of cancers, but
      its antineoplastic activity is limited in drug-resistant cancer cells. To
      investigate the detailed mechanism of 5-FU resistance, we developed a model of 5
      FU-resistant cells from HCT-8 cells, a well-established colorectal cancer cell
      line. We found that the drug-resistant cells demonstrated high expression of TCF4
      and beta-catenin, indicating an upregulated Wnt pathway. A microarray analysis
      revealed that the suppression of the checkpoint kinase 1 (CHK1) pathway explained
      the resistance to 5-FU, especially in p53 wild-type cancer cells such as HCT-8.
      Our data also demonstrated that the CHK1 pathway is suppressed by the Wnt pathway
      in 5-FU-resistant cells. In summary, we have discovered a novel mechanism for 5
      FU resistance mediated by histone deacetylation, which also revealed the
      crosstalk between the Wnt pathway and CHK1 pathway.

PMID- 30111798
TI  - Pyroxazone, a new neuroprotective compound from Streptomyces sp. RAN54.
AB  - A neuroprotective compound designated pyroxazone (1) was isolated from the
      culture broth of Streptomyces sp. RAN54. The molecular formula of 1 was
      established as C18H14N2O5 by high-resolution FAB-MS. The structure was determined
      to be a new 2-amino-3H-phenoxazin-3-one derivative by NMR spectroscopic analysis.
      Pyroxazone (1) protected C6 rat glioma cells and N18-RE-105 rat primary retina
      mouse neuroblastoma hybrid cells from glutamate-induced toxicity with EC50s of
      8.2 uM and 1.7 uM, respectively.

PMID- 30111799
TI  - Pullusurfactans A-E, new biosurfactants produced by Aureobasidium pullulans
      A11211-4-57 from a fleabane, Erigeron annus (L.) pers.
AB  - Yeast biosurfactants have potent applications in medical, cosmeceutical, and food
      industries due to their specific modes of action, low toxicity, and
      applicability. In this study, biosurfactant-producing yeasts were screened for
      various industrial applications. Among them, Aureobasidium pullulans strain
      A11211-4-57 with potent surfactant activity from fleabane flower, Erigeron annus
      (L.) pers., was selected. From culture supernatant of strain A11211-4-57, five
      new low-surface-tension chemicals designated as pullusurfactans A-E were
      identified through consecutive chromatography steps, involving ODS, silica gel,
      Sephadex LH-20, and ODS Sep-pak cartridge columns. Based on mass and NMR
      measurements, structures of pullusurfactans A-E were determined as myo-inositol
      lipids with molecular formulae of C20H35O9, C18H32O8, C20H35O9, C24H42O9, and
      C18H32O8, respectively. These compounds exhibited potent biosurfactant activities
      (22.90, 22.40, 32.28, 25.28, and 22.44 mN/m, respectively). These results suggest
      that these novel biosurfactants have potential use as biosurfactants in
      industrial aspect.

PMID- 30111802
TI  - Distributed natural gas venting offshore along the Cascadia margin.
AB  - Widespread gas venting along the Cascadia margin is investigated from acoustic
      water column data and reveals a nonuniform regional distribution of over 1100
      mapped acoustic flares. The highest number of flares occurs on the shelf, and the
      highest flare density is seen around the nutrition-rich outflow of the Juan de
      Fuca Strait. We determine ~430 flow-rates at ~340 individual flare locations
      along the margin with instantaneous in situ values ranging from ~6 mL min-1 to
      ~18 L min-1. Applying a tidal-modulation model, a depth-dependent methane
      density, and extrapolating these results across the margin using two
      normalization techniques yields a combined average in situ flow-rate of ~88 * 106
      kg y-1. The average methane flux-rate for the Cascadia margin is thus estimated
      to ~0.9 g y-1m-2. Combined uncertainties result in a range of these values
      between 4.5 and 1800% of the estimated mean values.

PMID- 30111800
TI  - Complex bile duct network formation within liver decellularized extracellular
      matrix hydrogels.
AB  - The biliary tree is an essential component of transplantable human liver tissue.
      Despite recent advances in liver tissue engineering, attempts at re-creating the
      intrahepatic biliary tree have not progressed significantly. The finer branches
      of the biliary tree are structurally and functionally complex and heterogeneous
      and require harnessing innate developmental processes for their regrowth. Here we
      demonstrate the ability of decellularized liver extracellular matrix (dECM)
      hydrogels to induce the in vitro formation of complex biliary networks using
      encapsulated immortalized mouse small biliary epithelial cells (cholangiocytes).
      This phenomenon is not observed using immortalized mouse large cholangiocytes, or
      with purified collagen 1 gels or Matrigel. We also show phenotypic stability via
      immunostaining for specific cholangiocyte markers. Moreover, tight junction
      formation and maturation was observed to occur between cholangiocytes, exhibiting
      polarization and transporter activity. To better define the mechanism of duct
      formation, we utilized three fluorescently labeled, but otherwise identical
      populations of cholangiocytes. The cells, in a proximity dependent manner, either
      branch out clonally, radiating from a single nucleation point, or assemble into
      multi-colored structures arising from separate populations. These findings
      present liver dECM as a promising biomaterial for intrahepatic bile duct tissue
      engineering and as a tool to study duct remodeling in vitro.

PMID- 30111803
TI  - Rheumatoid arthritis and the mucosal origins hypothesis: protection turns to
      destruction.
AB  - Individuals at high risk of developing seropositive rheumatoid arthritis (RA) can
      be identified for translational research and disease prevention studies through
      the presence of highly informative and predictive patterns of RA-related
      autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in the
      serum. In serologically positive individuals without arthritis, designated ACPA
      positive at risk, the presence of mucosal inflammatory processes associated with
      the presence of local ACPA production has been demonstrated. In other at-risk
      populations, local RA-related autoantibody production is present even in the
      absence of serum autoantibodies. Additionally, a proportion of at-risk
      individuals exhibit local mucosal ACPA production in the lung, as well as
      radiographic small-airway disease, sputum hypercellularity and increased
      neutrophil extracellular trap formation. Other mucosal sites in at-risk
      individuals also exhibit autoantibody production, inflammation and/or evidence of
      dysbiosis. As the proportion of individuals who exhibit such localized
      inflammation-associated ACPA production is substantially higher than the
      likelihood of an individual developing future RA, this finding raises the
      hypothesis that mucosal ACPAs have biologically relevant protective roles.
      Identifying the mechanisms that drive both the generation and loss of externally
      focused mucosal ACPA production and promote systemic autoantibody expression and
      ultimately arthritis development should provide insights into new therapeutic
      approaches to prevent RA.

PMID- 30111801
TI  - Unraveling the Plasmodium vivax sporozoite transcriptional journey from mosquito
      vector to human host.
AB  - Malaria parasites transmitted by mosquito bite are remarkably efficient in
      establishing human infections. The infection process requires roughly 30 minutes
      and is highly complex as quiescent sporozoites injected with mosquito saliva must
      be rapidly activated in the skin, migrate through the body, and infect the liver.
      This process is poorly understood for Plasmodium vivax due to low infectivity in
      the in vitro models. To study this skin-to-liver-stage of malaria, we used
      quantitative bioassays coupled with transcriptomics to evaluate parasite changes
      linked with mammalian microenvironmental factors. Our in vitro phenotyping and
      RNA-seq analyses revealed key microenvironmental relationships with distinct
      biological functions. Most notable, preservation of sporozoite quiescence by
      exposure to insect-like factors coupled with strategic activation limits untimely
      activation of invasion-associated genes to dramatically increase hepatocyte
      invasion rates. We also report the first transcriptomic analysis of the P. vivax
      sporozoite interaction in salivary glands identifying 118 infection-related
      differentially-regulated Anopheles dirus genes. These results provide important
      new insights in malaria parasite biology and identify priority targets for
      antimalarial therapeutic interventions to block P. vivax infection.

PMID- 30111804
TI  - Major lung complications of systemic sclerosis.
AB  - Systemic sclerosis (SSc) is associated with high mortality owing to internal
      organ complications, and lung disease is the leading cause of SSc-associated
      death. The most notable lung complications in SSc are fibrosis and pulmonary
      arterial hypertension (PAH). A major challenge for the management of lung disease
      in SSc is detecting those patients with severe pathology and those patients who
      are likely to benefit from available treatments. In the past few years,
      strategies for managing lung fibrosis and pulmonary hypertension, including PAH,
      have greatly progressed. For lung fibrosis, the tools to assess risk of
      progression and severity of the disease have been refined. Clinical trial results
      support the use of immunosuppression, including high-intensity regimens with
      autologous stem cell transplantation. New trials are underway to test other
      potential therapies including treatments that are approved for use in idiopathic
      lung fibrosis. For PAH, identifying individuals at high risk of disease
      development is critical. In addition, individuals who have borderline elevation
      of pulmonary arterial pressure need to be appropriately managed and followed up.
      Many approved drugs targeting PAH are now available, and results from large-scale
      clinical trials provide robust evidence that various treatments for SSc
      associated PAH are associated with good long-term outcomes.

PMID- 30111805
TI  - Method for the Destruction of Endotoxin in Synthetic Spider Silk Proteins.
AB  - Although synthetic spider silk has impressive potential as a biomaterial,
      endotoxin contamination of the spider silk proteins is a concern, regardless of
      the production method. The purpose of this research was to establish a
      standardized method to either remove or destroy the endotoxins present in
      synthetic spider silk proteins, such that the endotoxin level was consistently
      equal to or less than 0.25 EU/mL, the FDA limit for similar implant materials.
      Although dry heat is generally the preferred method for endotoxin destruction,
      heating the silk proteins to the necessary temperatures led to compromised
      mechanical properties in the resultant materials. In light of this, other
      endotoxin destruction methods were investigated, including caustic rinses and
      autoclaving. It was found that autoclaving synthetic spider silk protein dopes
      three times in a row consistently decreased the endotoxin level 10-20 fold,
      achieving levels at or below the desired level of 0.25 EU/mL. Products made from
      triple autoclaved silk dopes maintained mechanical properties comparable to
      products from untreated dopes while still maintaining low endotoxin levels.
      Triple autoclaving is an effective and scalable method for preparing synthetic
      spider silk proteins with endotoxin levels sufficiently low for use as
      biomaterials without compromising the mechanical properties of the materials.

PMID- 30111806
TI  - Practical Three-Minute Synthesis of Acid-Coated Fluorescent Carbon Dots with
      Tuneable Core Structure.
AB  - We report a one-pot, three-minute synthesis of carboxylic acid-decorated
      fluorescent carbon dots (COOH-FCDs) with tuneable core morphology dependent on
      the surface passivating agent. Mechanism investigations highlighted the presence
      of key pyrazine and polyhydroxyl aromatic motifs, which are formed from the
      degradation of glucosamine in the presence of a bifunctional linker bearing acid
      and amine groups. The novel COOH-FCDs are selective Fe3+ and hemin sensors.
      Furthermore, the FCDs are shown to be non-toxic, fluorescent bioimaging agents
      for cancer cells.

PMID- 30111807
TI  - Long non-coding RNA HOTAIR promotes tumorigenesis and forecasts a poor prognosis
      in cholangiocarcinoma.
AB  - Cholangiocarcinoma (CCA) arising from the neoplastic transformation of
      cholangiocytes with increasing incidence in the worldwide. Unfortunately, a large
      amount of CCA patients lost their chance for surgery because it is hard to
      diagnose in the early stages. Long non-coding RNAs (lncRNAs) is closely
      associated with development and progression of various malignant tumors. Hox
      transcript antisense intergenic (HOTAIR), a negative prognostic factor for
      patients with gastric, liver and pancreatic carcinoma. Its transcription levels
      and functional roles in CCA is still unknown. Therefore, we aimed to explore the
      effect of HOTAIR in CCA including cell proliferation, apoptosis, migration,
      invasion and epithelial-to-mesenchymal transition (EMT). The results showed that
      HOTAIR was highly expressed both in CCA tissue samples and cell lines compared
      with corresponding normal bile duct tissues and Human intrahepatic biliary
      epithelial cells (HIBEC). Its overexpression was closely correlated with Tumor
      size, TNM stage and postoperative recurrence in CCA patients. Moreover, up
      regulation of HOTAIR has correlation with prognosis in CCA patients. Knockdown of
      HOTAIR by siRNAs significantly decreased the migration and invasion but increased
      apoptosis of CCA cells in vitro. Overall, our study revealed that HOTAIR may play
      as a new potential therapeutic target and forecast poor prognosis for this fatal
      disease.

PMID- 30111808
TI  - Lower genital tract cytokine profiles in South African women living with HIV:
      influence of mucosal sampling.
AB  - Measurement of cytokines in the lower female genital tract offer insight into
      risk for HIV infection and reproductive complications. However, few studies have
      systematically compared mucosal collection methods or whether collection order
      matters. We compared longitudinal cytokine profiles in matched genital samples
      collected from women living with HIV using menstrual cup (MC), endocervical swabs
      (ECS) and swab-enriched cervicovaginal lavage (eCVL). Samples were collected at
      enrollment [MC:ECS:eCVL], 3-months (ECS:eCVL:MC) and 6-months (eCVL:MC:ECS) and
      concentrations of 28 cytokines determined by Luminex. Cytokine clustering was
      assessed using Principle Component Analysis (PCA), Partial Least Squares
      Discriminant Analysis (PLSDA) and factor analysis. Generally, higher cytokine
      concentrations were detected in MC samples, followed by ECS and eCVL,
      irrespective of study visit or sampling order. Factor analysis and PCA identified
      ECS to be inferior for measuring regulatory cytokines and IP-10 than eCVL or MC.
      Although concentrations differed, the majority of cytokines correlated between
      methods. Sampling order influenced cytokine concentrations marginally, and
      cytokines clustered more strongly by method than study visit. Variance in
      profiles was lowest in MC, suggesting greater consistency of sampling compared to
      other methods. We conclude that MC sampling offered advantages over other methods
      for detecting cytokines in women, with order marginally influencing profiles.

PMID- 30111809
TI  - Aristolochic acid I determine the phenotype and activation of macrophages in
      acute and chronic kidney disease.
AB  - Acute and chronic kidney injuries are multifactorial traits that involve various
      risk factors. Experimental animal models are crucial to unravel important aspects
      of injury and its pathophysiological mechanisms. Translating knowledge obtained
      from experimental approaches into clinically useful information is difficult;
      therefore, significant attention needs to be paid to experimental procedures that
      mimic human disease. Herein, we compared aristolochic acid I (AAI) acute and
      chronic kidney injury model with unilateral ischemic-reperfusion injury (uIRI),
      cisplatin (CP)- or folic acid (FA)-induced renal damage. The administration of
      AAI showed significant changes in serum creatinine and BUN upon CKD. The number
      of neutrophils and macrophages were highly increased as well as AAI-induced CKD
      characterized by loss of tubular epithelial cells and fibrosis. The in vitro and
      in vivo data indicated that macrophages play an important role in the
      pathogenesis of AA-induced nephropathy (AAN) associated with an excessive
      macrophage accumulation and an alternative activated macrophage phenotype. Taken
      together, we conclude that AA-induced injury represents a suitable and relatively
      easy model to induce acute and chronic kidney injury. Moreover, our data indicate
      that this model is appropriate and superior to study detailed questions
      associated with renal macrophage phenotypes.

PMID- 30111810
TI  - A direct interaction between two Restless Legs Syndrome predisposing genes: MEIS1
      and SKOR1.
AB  - Restless Legs syndrome (RLS) is a common sleep disorder for which the genetic
      contribution remains poorly explained. In 2007, the first large scale genome wide
      association study (GWAS) identified three genomic regions associated with RLS.
      MEIS1, BTBD9 and MAP2K5/SKOR1 are the only known genes located within these loci
      and their association with RLS was subsequently confirmed in a number of follow
      up GWAS. Following this finding, our group reported the MEIS1 risk haplotype to
      be associated with its decreased expression at the mRNA and protein levels. Here
      we report the effect of the risk variants of the three other genes strongly
      associated with RLS. While these variants had no effect on the mRNA levels of the
      genes harboring them, we find that the homeobox transcription factor MEIS1
      positively regulates the expression of the transcription co-repressor SKOR1. This
      regulation appears mediated through the binding of MEIS1 at two specific sites
      located in the SKOR1 promoter region and is modified by an RLS associated SNP in
      the promoter region of the gene. Our findings directly link MEIS1 and SKOR1, two
      significantly associated genes with RLS and also prioritize SKOR1 over MAP2K5 in
      the RLS associated intergenic region of MAP2K5/SKOR1 found by GWAS.

PMID- 30111812
TI  - PKMzeta in the nucleus accumbens acts to dampen cocaine seeking.
AB  - The constitutively active, atypical protein kinase C, protein kinase M-zeta
      (PKMzeta), is exclusively expressed in the brain and its expression increases
      following exposure to drugs of abuse. However, the limitations of currently
      available tools have made it difficult to examine the role of PKMzeta in cocaine
      self-administration and relapse. The current study demonstrates that constitutive
      deletion of PKMzeta potentiates cue-induced reinstatement of cocaine seeking and
      increases both food and cocaine self-administration, without affecting cue-driven
      food seeking in both male and female mice. Conditional deletion of PKMzeta within
      the nucleus accumbens recapitulated the increase in cocaine taking and seeking
      seen in the constitutive knockout mice, but only in male animals. Site-specific
      knockdown of PKMzeta in the nucleus accumbens had no effect on cocaine taking or
      seeking in female mice. Additionally, neither male nor female mice exhibited any
      alterations in food self-administration or cue-induced reinstatement of food
      seeking following accumbal deletion of PKMzeta. Taken together these results
      indicate that PKMzeta may act to dampen cocaine taking and seeking. Furthermore,
      these results indicate that PKMzeta is playing divergent roles in reward seeking
      in males and females.

PMID- 30111813
TI  - Role of hydration energy and co-ions association on monovalent and divalent
      cations adsorption at mica-aqueous interface.
AB  - Adsorption of ions at the solid - aqueous interface is the primary mechanism in
      fast biological processes to very slow geological transformations. Despite,
      little is known about role of ion charge, hydration energy and hydration
      structure on competitive adsorption of ions, their structure and coverage at the
      interface. In this report, we investigate the structure and adsorption behavior
      of monovalent (Rb+ and Na+) and divalent (Sr2+ and Mg2+) cations ranging from 0
      4.5 M of bulk concentrations on the muscovite mica surface. Divalent ions have
      stronger adsorption strength compared to monovalent ions due higher charge.
      However, we observed counter-intuitive behavior of lesser adsorption of divalent
      cations compared to monovalent cations. Our detailed analysis reveals that
      hydration structure of divalent cations hinders their adsorption. Both, Na+ and
      Rb+ ions exhibits similar adsorption behavior, however, the adsorption mechanism
      of Na+ ions is different from Rb+ ions in terms of redistribution of the water
      molecules in their hydration shell. In addition, we observed surface mediated
      RbCl salting out behavior, which is absent in Na+ and divalent ions. We observed
      direct correlation in hydration energy of cations and their adsorption behavior.
      The obtained understanding will have tremendous impact in super-capacitors,
      nanotribology, colloidal chemistry and water purifications.

PMID- 30111814
TI  - Angiogenic response of rat hippocampal vasculature to focused ultrasound-mediated
      increases in blood-brain barrier permeability.
AB  - Focused ultrasound (FUS) and circulating microbubbles can induce a targeted and
      transient increase in blood-brain barrier permeability. While preclinical
      research has demonstrated the utility of FUS for efficacious drug deliver to the
      brain, there remain gaps in our knowledge regarding the long-term response of
      brain vasculature to this intervention. Previous work has demonstrated
      transcriptional changes in hippocampal microvessels following sonication that are
      indicative of the initiation of angiogenic processes. Moreover, blood vessel
      growth has been reported in skeletal muscle following application of FUS and
      microbubbles. The current study demonstrates that blood vessel density in the rat
      hippocampus is modestly elevated at 7 and 14 d post-FUS compared to the
      contralateral hemisphere (7 d: 10.9 +/- 6.0%, p = 0.02; 14 d: 12.1 +/- 3.2%, p <
      0.01), but returns to baseline by 21 d (5.9 +/- 2.6%, p = 0.12). Concurrently,
      relative newborn endothelial cell density and frequency of small blood vessel
      segments were both elevated in the sonicated hippocampus. While further work is
      required to determine the mechanisms driving these changes, the findings
      presented here may have relevance to the optimal frequency of repeated
      treatments.

PMID- 30111815
TI  - 21st-century modeled permafrost carbon emissions accelerated by abrupt thaw
      beneath lakes.
AB  - Permafrost carbon feedback (PCF) modeling has focused on gradual thaw of near
      surface permafrost leading to enhanced carbon dioxide and methane emissions that
      accelerate global climate warming. These state-of-the-art land models have yet to
      incorporate deeper, abrupt thaw in the PCF. Here we use model data, supported by
      field observations, radiocarbon dating, and remote sensing, to show that methane
      and carbon dioxide emissions from abrupt thaw beneath thermokarst lakes will more
      than double radiative forcing from circumpolar permafrost-soil carbon fluxes this
      century. Abrupt thaw lake emissions are similar under moderate and high
      representative concentration pathways (RCP4.5 and RCP8.5), but their relative
      contribution to the PCF is much larger under the moderate warming scenario.
      Abrupt thaw accelerates mobilization of deeply frozen, ancient carbon, increasing
      14C-depleted permafrost soil carbon emissions by ~125-190% compared to gradual
      thaw alone. These findings demonstrate the need to incorporate abrupt thaw
      processes in earth system models for more comprehensive projection of the PCF
      this century.

PMID- 30111811
TI  - Sex differences in the hypothalamic-pituitary-adrenal axis' response to stress:
      an important role for gonadal hormones.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine network that
      controls hormonal responses to internal and external challenges in an organism's
      environment, exhibits strikingly sex-biased activity. In adult female rodents,
      acute HPA function following a stressor is markedly greater than it is in males,
      and this difference has largely been attributed to modulation by the gonadal
      hormones testosterone and estradiol. These gonadal hormones are produced by the
      hypothalamic-pituitary-gonadal (HPG) axis and have been shown to determine sex
      differences in adult HPA function after acute stress via their activational and
      organizational effects. Although these actions of gonadal hormones are well
      supported, the possibility that sex chromosomes similarly influence HPA activity
      is unexplored. Moreover, questions remain regarding sex differences in the
      activity of the HPA axis following chronic stress and the underlying
      contributions of gonadal hormones and sex chromosomes. The present review
      examines what is currently known about sex differences in the neuroendocrine
      response to stress, as well as outstanding questions regarding this sex bias.
      Although it primarily focuses on the rodent literature, a brief discussion of sex
      differences in the human HPA axis is also included.

PMID- 30111817
TI  - Epithelial-mesenchymal transition (EMT) beyond EGFR mutations per se is a common
      mechanism for acquired resistance to EGFR TKI.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is a
      major advance in treating NSCLC with EGFR-activating mutations. However, acquired
      resistance, due partially to secondary mutations limits their use. Here we report
      that NSCLC cells with acquired resistance to gefitinib or osimertinib (AZD9291)
      exhibit EMT features, with a decrease in E-cadherin, and increases in vimentin
      and stemness, without possessing any EGFR secondary mutations. Knockdown of E
      cadherin in parental cells increased gefitinib resistance and stemness, while
      knockdown of vimentin in resistant cells resulted in opposite effects. Src
      activation and Hakai upregulation were found in gefitinib-resistant cells.
      Knockdown of Hakai elevated E-cadherin expression, attenuated stemness, and
      resensitized the cells to gefitinib. Clinical cancer specimens with acquired
      gefitinib resistance also showed a decrease in E-cadherin and an increase in
      Hakai expression. The dual HDAC and HMGR inhibitor JMF3086 inhibited the
      Src/Hakai and Hakai/E-cadherin interaction to reverse E-cadherin expression, and
      attenuated vimentin and stemness to restore gefitinib sensitivity. The EMT
      features of AZD9291-resistant H1975 cells were related to the upregulation of
      Zeb1. Both gefitinib and AZD9291 sensitivity was restored by JMF3086 through
      reversing EMT. Our study not only revealed a common mechanism of EMT in both
      gefitinib and AZD9291 resistance beyond EGFR mutations per se, but also provides
      a new strategy to overcome it.

PMID- 30111816
TI  - Derivation of induced pluripotent stem cells in Japanese macaque (Macaca
      fuscata).
AB  - Non-human primates are our closest relatives and are of special interest for
      ecological, evolutionary and biomedical research. The Japanese macaque (Macaca
      fuscata) has contributed to the progress of primatology and neurosciences over 60
      years. Despite this importance, the molecular and cellular basis of the Japanese
      macaque remains unexplored since useful cellular tools are lacking. Here we
      generated induced pluripotent stem cells (iPSCs) from skin fibroblasts of the
      Japanese macaque with Sendai virus or plasmid vectors. The Japanese macaque iPSCs
      (jm-iPSCs) were established under feeder-free culture conditions, but feeder
      cells turned out to be essential for their maintenance. The jm-iPSCs formed human
      iPSC-like flat colonies which were positive for pluripotent antigens including
      alkaline phosphatase, SSEA4, and TRA-1-81. They also expressed endogenous OCT3/4,
      SOX2, L-MYC, and KLF4 and other pluripotent marker genes. The potential to
      differentiate into all three germ layers and neural stem cells was confirmed by
      embryoid body and neurosphere formation, respectively. The jm-iPSCs will provide
      a robust in vitro tool for investigating the underlying mechanisms of development
      and physiology studies with the Japanese macaque.

PMID- 30111818
TI  - A novel cross-talk between CXCR4 and PI4KIIIalpha in prostate cancer cells.
AB  - Chemokine signaling regulates cell migration and tumor metastasis. CXCL12, a
      member of the chemokine family, and its receptor, CXCR4, a G protein coupled
      receptor (GPCR), are key mediators of prostate-cancer (PC) bone metastasis. In PC
      cells androgens activate CXCR4 gene expression and receptor signaling on lipid
      rafts, which induces protease expression and cancer cell invasion. To identify
      novel lipid-raft-associated CXCR4 regulators supporting invasion/metastasis, we
      performed a SILAC-based quantitative proteomic analysis of lipid-rafts derived
      from PC3 stable cell lines with overexpression or knockdown of CXCR4. This
      analysis identified the evolutionarily conserved phosphatidylinositol 4-kinase
      IIIalpha (PI4KIIIalpha), and SAC1 phosphatase that dephosphorylates
      phosphatidylinositol-4-phosphate as potential candidate CXCR4 regulators. CXCR4
      interacted with PI4KIIIalpha membrane targeting machinery recruiting them to the
      plasma membrane for PI4P production. Consistent with this interaction,
      PI4KIIIalpha was found tightly linked to the CXCR4 induced PC cell invasion.
      Thus, ablation of PI4KIIIalpha in CXCR4-expressing PC3 cells reduced cellular
      invasion in response to a variety of chemokines. Immunofluorescence microscopy in
      CXCR4-expressing cells revealed localized production of PI4P on the invasive
      projections. Human tumor studies documented increased PI4KIIIalpha expression in
      metastatic tumors vs. the primary tumor counterparts, further supporting the
      PI4KIIIalpha role in tumor metastasis. Furthermore, we also identified an
      unexpected function of PI4KIIIalpha in GPCR signaling where CXCR4 regulates
      PI4KIIIalpha activity and mediate tumor metastasis. Altogether, our study
      identifies a novel cross-talk between PI4KIIIalpha and CXCR4 in promoting tumor
      metastasis and suggests that PI4KIIIalpha pharmacological targeting may have
      therapeutic benefit for advanced prostate cancer patients.

PMID- 30111819
TI  - Inhibition of histone lysine-specific demethylase 1 elicits breast tumor immunity
      and enhances antitumor efficacy of immune checkpoint blockade.
AB  - Immunotherapy strategies have been emerging as powerful weapons against cancer.
      Early clinical trials reveal that overall response to immunotherapy is low in
      breast cancer patients, suggesting that effective strategies to overcome
      resistance to immunotherapy are urgently needed. In this study, we investigated
      whether epigenetic reprograming by modulating histone methylation could enhance
      effector T lymphocyte trafficking and improve therapeutic efficacy of immune
      checkpoint blockade in breast cancer with focus on triple-negative breast cancer
      (TNBC) subtype. In silico analysis of The Cancer Genome Atlas (TCGA) data shows
      that expression of histone lysine-specific demethylase 1 (LSD1) is inversely
      associated with the levels of cytotoxic T cell-attracting chemokines (C-C motif
      chemokine ligand 5 (CCL5), C-X-C motif chemokine ligand 9 and 10 (CXCL9, CXCL10))
      and programmed death-ligand 1 (PD-L1) in clinical TNBC specimens. Tiling
      chromatin immunoprecipitation study showed that re-expression of chemokines by
      LSD1 inhibition is associated with increased H3K4me2 levels at proximal promoter
      regions. Rescue experiments using concurrent treatment with small interfering RNA
      or inhibitor of chemokine receptors blocked LSD1 inhibitor-enhanced CD8+ T cell
      migration, indicating a critical role of key T cell chemokines in LSD1-mediated
      CD8+ lymphocyte trafficking to the tumor microenvironment. In mice bearing TNBC
      xenograft tumors, anti-PD-1 antibody alone failed to elicit obvious therapeutic
      effect. However, combining LSD1 inhibitors with PD-1 antibody significantly
      suppressed tumor growth and pulmonary metastasis, which was associated with
      reduced Ki-67 level and augmented CD8+ T cell infiltration in xenograft tumors.
      Overall, these results suggest that LSD1 inhibition may be an effective adjuvant
      treatment with immunotherapy as a novel management strategy for poorly
      immunogenic breast tumors.

PMID- 30111821
TI  - Synergistic negative effects of thermal stress and altered food resources on
      echinoid larvae.
AB  - Multiple changes to the marine environment under climate change can have additive
      or interactive (antagonistic or synergistic) effects on marine organisms.
      Prompted by observations of anomalously warm sea temperatures and low chlorophyll
      concentrations during the 2013-2016 warm "Blob" event in the Northeast Pacific
      Ocean, we examined the combined effects of thermal stress and a shift in food
      resources on the development of a larval echinoid (Strongylocentrotus
      droebachiensis) in the laboratory. A high concentration of phytoplankton yielded
      faster echinus rudiment development at warm versus historical temperature,
      indicating a mitigating effect of abundant food on thermal stress; however, low
      phytoplankton concentration or a shift in diet to suspended kelp detritus,
      yielded slow development and high mortality at warm temperature. The results
      indicate a synergistic negative effect of thermal stress and altered food
      resources on larvae of a keystone marine species.

PMID- 30111820
TI  - Gene essentiality landscape and druggable oncogenic dependencies in herpesviral
      primary effusion lymphoma.
AB  - Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated
      herpesvirus. Our understanding of PEL is poor and therefore treatment strategies
      are lacking. To address this need, we conducted genome-wide CRISPR/Cas9 knockout
      screens in eight PEL cell lines. Integration with data from unrelated cancers
      identifies 210 genes as PEL-specific oncogenic dependencies. Genetic requirements
      of PEL cell lines are largely independent of Epstein-Barr virus co-infection.
      Genes of the NF-kappaB pathway are individually non-essential. Instead, we
      demonstrate requirements for IRF4 and MDM2. PEL cell lines depend on cellular
      cyclin D2 and c-FLIP despite expression of viral homologs. Moreover, PEL cell
      lines are addicted to high levels of MCL1 expression, which are also evident in
      PEL tumors. Strong dependencies on cyclin D2 and MCL1 render PEL cell lines
      highly sensitive to palbociclib and S63845. In summary, this work comprehensively
      identifies genetic dependencies in PEL cell lines and identifies novel strategies
      for therapeutic intervention.

PMID- 30111822
TI  - Changes in the gut microbiota composition during pregnancy in patients with
      gestational diabetes mellitus (GDM).
AB  - Gestational diabetes mellitus (GDM), a common pregnancy complication, is
      associated with an increased risk of maternal/perinatal outcomes. We performed a
      prospective observational explorative study in 41 GDM patients to evaluate their
      microbiota changes during pregnancy and the associations between the gut
      microbiota and variations in nutrient intakes, anthropometric and laboratory
      variables. GDM patients routinely received nutritional recommendations according
      to guidelines. The fecal microbiota (by 16S amplicon-based sequencing), was
      assessed at enrolment (24-28 weeks) and at 38 weeks of gestational age. At the
      study end, the microbiota alpha-diversity significantly increased (P < 0.001),
      with increase of Firmicutes and reduction of Bacteroidetes and Actinobacteria.
      Patients who were adherent to the dietary recommendations showed a better
      metabolic and inflammatory pattern at the study-end and a significant decrease in
      Bacteroides. In multiple regression models, Faecalibacterium was significantly
      associated with fasting glucose; Collinsella (directly) and Blautia (inversely)
      with insulin, and with Homeostasis-Model Assessment Insulin-Resistance, while
      Sutterella with C-reactive protein levels. Consistent with this latter
      association, the predicted metagenomes showed a correlation between those taxa
      and inferred KEGG genes associated with lipopolysaccharide biosynthesis. A higher
      bacterial richness and strong correlations between pro-inflammatory taxa and
      metabolic/inflammatory variables were detected in GDM patients across pregnancy.
      Collectively these findings suggest that the development of strategies to
      modulate the gut microbiota might be a potentially useful tool to impact on
      maternal metabolic health.

PMID- 30111824
TI  - Maximal distant entanglement in Kitaev tube.
AB  - We study the Kitaev model on a finite-size square lattice with periodic boundary
      conditions in one direction and open boundary conditions in the other. Based on
      the fact that the Majorana representation of Kitaev model is equivalent to a
      brick wall model under the condition t = Delta = MU, this system is shown to
      support perfect Majorana bound states which is in strong localization limit. By
      introducing edge-mode fermionic operator and pseudo-spin representation, we find
      that such edge modes are always associated with maximal entanglement between two
      edges of the tube, which is independent of the size of the system.

PMID- 30111823
TI  - Peripubertal stress increases play fighting at adolescence and modulates nucleus
      accumbens CB1 receptor expression and mitochondrial function in the amygdala.
AB  - Play fighting is a highly rewarding behavior that helps individuals to develop
      social skills. Early-life stress has been shown to alter play fighting in rats
      and hamsters as well as to increase aggressive behaviors at adulthood. However,
      it is not known whether individual differences in stress-induced play fighting
      are related to differential developmental trajectories towards adult aggression.
      To address this question, we used a rat model of peripubertal stress (PPS)
      induced psychopathology that involves increased aggression at adulthood. We
      report that, indeed, PPS leads to enhanced play fighting at adolescence. Using a
      stratification approach, we identify individuals with heightened levels of play
      fighting as the ones that show abnormal forms of aggression at adulthood. These
      animals showed as well a rapid habituation of their corticosterone responsiveness
      to repeated stressor exposure at peripuberty. They also showed a striking
      increase in mitochondrial function in the amygdala-but not nucleus accumbens-when
      tested ex vivo. Conversely, low, but not high players, displayed increased
      expression of the CB1 cannabinoid receptor in the nucleus accumbens shell. Our
      results highlight adolescence as a potential critical period in which aberrant
      play fighting is linked to the emergence of adult aggression. They also point at
      brain energy metabolism during adolescence as a possible target to prevent adult
      aggression.

PMID- 30111826
TI  - Quantification of the ozone and singlet delta oxygen produced in gas and liquid
      phases by a non-thermal atmospheric plasma with relevance for medical treatment.
AB  - In the field of plasma medicine, the identification of relevant reactive species
      in the liquid phase is highly important. To design the plasma generated species
      composition for a targeted therapeutic application, the point of origin of those
      species needs to be known. The dominant reactive oxygen species generated by the
      plasma used in this study are atomic oxygen, ozone, and singlet delta oxygen. The
      species density changes with the distance to the active plasma zone, and, hence,
      the oxidizing potential of this species cocktail can be tuned by altering the
      treatment distance. In both phases (gas and liquid), independent techniques have
      been used to determine the species concentration as a function of the distance.
      The surrounding gas composition and ambient conditions were controlled between
      pure nitrogen and air-like by using a curtain gas device. In the gas phase, in
      contrast to the ozone density, the singlet delta oxygen density showed to be more
      sensitive to the distance. Additionally, by changing the surrounding gas,
      admixing or not molecular oxygen, the dynamics of ozone and singlet delta oxygen
      behave differently. Through an analysis of the reactive species development for
      the varied experimental parameters, the importance of several reaction pathways
      for the proceeding reactions was evaluated and some were eventually excluded.

PMID- 30111825
TI  - Early molecular events associated with nitrogen deficiency in rice seedling
      roots.
AB  - Nitrogen (N) deficiency is one of the most common problems in rice. The symptoms
      of N deficiency are well documented, but the underlying molecular mechanisms are
      largely unknown in rice. Here, we studied the early molecular events associated
      with N starvation (-N, 1 h), focusing on amino acid analysis and identification
      of -N-regulated genes in rice roots. Interestingly, levels of glutamine rapidly
      decreased within 15 min of -N treatment, indicating that part of the N-deficient
      signals could be mediated by glutamine. Transcriptome analysis revealed that
      genes involved in metabolism, plant hormone signal transduction (e.g. abscisic
      acid, auxin, and jasmonate), transporter activity, and oxidative stress responses
      were rapidly regulated by -N. Some of the -N-regulated genes encode transcription
      factors, protein kinases and protein phosphatases, which may be involved in the
      regulation of early -N responses in rice roots. Previously, we used similar
      approaches to identify glutamine-, glutamate-, and ammonium nitrate-responsive
      genes. Comparisons of the genes induced by different forms of N with the -N
      regulated genes identified here have provided a catalog of potential N regulatory
      genes for further dissection of the N signaling pathwys in rice.

PMID- 30111828
TI  - Improvement of physico-chemical properties of dextran-chitosan composite
      scaffolds by addition of nano-hydroxyapatite.
AB  - Nano-hydroxyapatite was incorporated into polymer matrix of Dextran/Chitosan to
      achieve a novel composite scaffold by freeze drying technique. The synthesized
      composite scaffolds were recognized by different performances such as: X-ray
      diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and Scanning
      electron microscope (SEM). The results revealed the complex formation between
      dextran and chitosan with an excellent dispersion of nHA inside the polymer
      matrix. The SEM images showed the presence of interconnected pore structure
      inside the scaffolds. The porosity of the composites was found to decrease from
      82% to 67% by adding nanohydroxyapatite to the polymer matrix of
      Dextran/Chitosan. The mechanical properties of the scaffolds were measured by
      compression test. The obtained results verified that the presence of nHA can
      noticeably enhance young's modulus and compressive strength of the composite
      scaffolds. All the obtained results essentially recommend that these composites
      can be a good candidate for bone tissue engineering applications.

PMID- 30111827
TI  - Machine learning for fast identification of bacteraemia in SIRS patients treated
      on standard care wards: a cohort study.
AB  - Bacteraemia is a life-threating condition requiring immediate diagnostic and
      therapeutic actions. Blood culture (BC) analyses often result in a low true
      positive result rate, indicating its improper usage. A predictive model might
      assist clinicians in deciding for whom to conduct or to avoid BC analysis in
      patients having a relevant bacteraemia risk. Predictive models were established
      by using linear and non-linear machine learning methods. To obtain proper data, a
      unique data set was collected prior to model estimation in a prospective cohort
      study, screening 3,370 standard care patients with suspected bacteraemia. Data
      from 466 patients fulfilling two or more systemic inflammatory response syndrome
      criteria (bacteraemia rate: 28.8%) were finally used. A 29 parameter panel of
      clinical data, cytokine expression levels and standard laboratory markers was
      used for model training. Model tuning was performed in a ten-fold cross
      validation and tuned models were validated in a test set (80:20 random split).
      The random forest strategy presented the best result in the test set validation
      (ROC-AUC: 0.729, 95%CI: 0.679-0.779). However, procalcitonin (PCT), as the best
      individual variable, yielded a similar ROC-AUC (0.729, 95%CI: 0.679-0.779). Thus,
      machine learning methods failed to improve the moderate diagnostic accuracy of
      PCT.

PMID- 30111830
TI  - Understanding explosive diversification through cichlid fish genomics.
AB  - Owing to their taxonomic, phenotypic, ecological and behavioural diversity and
      propensity for explosive diversification, the assemblages of cichlid fish in the
      East African Great Lakes Victoria, Malawi and Tanganyika are important role
      models in evolutionary biology. With the release of five reference genomes and
      many additional genomic resources, as well as the establishment of functional
      genomic tools, the cichlid system has fully entered the genomic era. The in-depth
      genomic exploration of the East African cichlid fauna - in combination with the
      examination of their ecology, morphology and behaviour - permits novel insights
      into the way organisms diversify.

PMID- 30111829
TI  - Plasma Homoarginine Concentrations According to Use of Hormonal Contraception.
AB  - Estrogen is a potent vasodilator through activation of endothelial nitric oxide
      synthase (eNOS). Arginine and its homologue homoarginine are substrates for NOS,
      while asymmetric dimethylarginine (ADMA) is a NOS inhibitor. Healthy, never
      pregnant women aged 18 to 40 years (n = 158) were categorized according to use of
      hormonal contraception into non-users (n = 76), users of estrogen contraceptives
      (EC-users, n = 58) and users of progestins-only contraceptives (PC-users, n =
      24). Plasma homoarginine, arginine, ADMA and SDMA concentrations were assayed
      using a LC-MS/MS method. Compared to non-users, EC users had higher plasma
      homoarginine (median (interquartile range) 1.63 (1.24, 2.04) vs. 2.39 (2.05,
      2.85) umol/L, p < 0.001), lower arginine (80.8 (72.4, 94.3) vs. 72.1 (62.9, 85.1)
      umol/L, p = 0.008) and ADMA (0.52 (0.46, 0.59) vs. 0.48 (0.42, 0.54) umol/L, p =
      0.003) concentrations. The lowest median plasma homoarginine concentration (1.34
      (0.92, 1.75) umol) was seen in PC-users. No differences were seen in SDMA
      concentrations according to use of hormonal contraception. In healthy, never
      pregnant women aged 18 to 40 years, use of estrogen containing contraception was
      associated with significantly higher plasma concentrations of homoarginine and
      lower plasma concentrations of arginine and ADMA as compared to non-users, while
      the lowest plasma homoarginine concentrations were seen in progestin-only users.
      Whether the observed changes in relation to use of hormonal contraception have an
      impact on cardiovascular status, should be evaluated in an intervention study.

PMID- 30111831
TI  - Subcellular Peptide Localization in Single Identified Neurons by Capillary
      Microsampling Mass Spectrometry.
AB  - Single cell mass spectrometry (MS) is uniquely positioned for the sequencing and
      identification of peptides in rare cells. Small peptides can take on different
      roles in subcellular compartments. Whereas some peptides serve as
      neurotransmitters in the cytoplasm, they can also function as transcription
      factors in the nucleus. Thus, there is a need to analyze the subcellular peptide
      compositions in identified single cells. Here, we apply capillary microsampling
      MS with ion mobility separation for the sequencing of peptides in single neurons
      of the mollusk Lymnaea stagnalis, and the analysis of peptide distributions
      between the cytoplasm and nucleus of identified single neurons that are known to
      express cardioactive Phe-Met-Arg-Phe amide-like (FMRFamide-like) neuropeptides.
      Nuclei and cytoplasm of Type 1 and Type 2 F group (Fgp) neurons were analyzed for
      neuropeptides cleaved from the protein precursors encoded by alternative splicing
      products of the FMRFamide gene. Relative abundances of nine neuropeptides were
      determined in the cytoplasm. The nuclei contained six of these peptides at
      different abundances. Enabled by its relative enrichment in Fgp neurons, a new 28
      residue neuropeptide was sequenced by tandem MS.

PMID- 30111832
TI  - Context-Dependent Regulation of Conjunctival Goblet Cell Function by Allergic
      Mediators.
AB  - In the eye, goblet cells responsible for secreting mucins are found in the
      conjunctiva. When mucin production is not tightly regulated several ocular
      surface disorders may occur. In this study, the effect of the T helper (Th) 2
      type cytokines IL4, IL5, and IL13 on conjunctival goblet cell function was
      explored. Goblet cells from rat conjunctiva were cultured and characterized. The
      presence of cytokine receptors was confirmed by Reverse Transcription-Polymerase
      Chain Reaction (RT-PCR). Changes in intracellular [Ca2+], high molecular weight
      glycoconjugate secretion, and proliferation were measured after stimulation with
      Th2 cytokines with or without the allergic mediator histamine. We found that IL4
      and IL13 enhance cell proliferation and, along with histamine, stimulate goblet
      cell secretion. We conclude that the high levels of IL4, IL5, and IL13 that
      characterize allergic conjunctivitis could be the reason for higher numbers of
      goblet cells and mucin overproduction found in this condition.

PMID- 30111833
TI  - Apoptosis regulation by subcellular relocation of caspases.
AB  - The cleavage of nuclear proteins by caspases promotes nuclear breakdown and,
      therefore, plays a key role in apoptosis execution. However, the detailed
      molecular mechanisms of these events remain unclear. To get more insights into
      the mechanisms of nuclear events during apoptosis we set up a rapid fractionation
      protocol for the separation of the cytoplasmic and nuclear fractions of cells
      undergoing cisplatin-induced apoptosis. Importantly, nuclear accumulation of
      effector caspase-3 as well as initiator caspase-2, -8 and -9 was observed using
      the developed protocol and immunofluorescence microscopy. The detection of
      caspases and their cleavage products in the nucleus occurred within the same time
      interval after cisplatin treatment and took place shortly before nuclear
      fragmentation. The entry of initiator caspases to the nucleus was independent of
      caspase-3. Given that all three initiator caspases had catalytic activity in the
      nuclei, our findings indicate that initiator caspases might participate in the
      proteolysis of nuclear components during apoptosis, promoting its disintegration
      and apoptotic cell death.

PMID- 30111834
TI  - The IRE1alpha-XBP1s pathway promotes insulin-stimulated glucose uptake in
      adipocytes by increasing PPARgamma activity.
AB  - The peroxisome proliferator-activated receptor-gamma (PPARgamma) improves whole
      body insulin sensitivity by regulating the adipogenic and metabolic functions of
      mature adipocytes. We have previously demonstrated that an active splice variant
      of X-box binding protein 1 (XBP1s) enhances PPARgamma expression during
      adipogenesis. In this study, we investigated the role of XBP1s, particularly with
      respect to PPARgamma, in the mechanisms underlying insulin sensitivity in mature
      adipocytes. Insulin was able to stimulate XBP1s generation by activating inositol
      requiring enzyme 1 (IRE1) alpha and was also able to increase its transcriptional
      activity by inducing nuclear translocation. XBP1s also upregulated the levels of
      phosphorylated IRS1 and AKT, demonstrating a positive feedback regulatory
      mechanism linking insulin and XBP1s. XBP1s enhanced the expression of fibroblast
      growth factor 21 and, in turn, increased PPARgamma activity, translocation of
      GLUT4 to the cell surface, and glucose uptake rate in adipocytes. In addition,
      XBP1s abolished palmitate-induced insulin resistance in adipocytes by increasing
      adiponectin secretion, repressing the secretion of pro-inflammatory adipokines
      such as leptin, monocyte chemoattractant protein 1, and tumor necrosis factor
      alpha, and decreasing fatty acid release. These findings provide a novel
      mechanism by which XBP1s stimulate insulin sensitivity in adipocytes through
      fibroblast growth factor 21 induction and PPARgamma activation.

PMID- 30111835
TI  - Transcriptional activation of glucose transporter 1 in orthodontic tooth movement
      associated mechanical response.
AB  - The interplay between mechanoresponses and a broad range of fundamental
      biological processes, such as cell cycle progression, growth and differentiation,
      has been extensively investigated. However, metabolic regulation in
      mechanobiology remains largely unexplored. Here, we identified glucose
      transporter 1 (GLUT1)-the primary glucose transporter in various cells-as a novel
      mechanosensitive gene in orthodontic tooth movement (OTM). Using an in vivo rat
      OTM model, we demonstrated the specific induction of Glut1 proteins on the
      compressive side of a physically strained periodontal ligament. This
      transcriptional activation could be recapitulated in in vitro cultured human
      periodontal ligament cells (PDLCs), showing a time- and dose-dependent
      mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117
      greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM
      model, and this reduction was associated with a decline in osteoclastic
      activities. A mechanistic study suggested that GLUT1 inhibition affected the
      receptor activator for nuclear factor-kappa B Ligand (RANKL)/osteoprotegerin
      (OPG) system by impairing compressive force-mediated RANKL upregulation.
      Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic
      differentiation of co-cultured RAW264.7 cells. Further biochemical analysis
      indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay
      potential communication between glucose uptake and mechanical stress response.
      Together, these cross-species experiments revealed the transcriptional activation
      of GLUT1 as a novel and conserved linkage between metabolism and bone
      remodelling.

PMID- 30111837
TI  - Sulfoxaflor exposure reduces bumblebee reproductive success.
AB  - Intensive agriculture currently relies on pesticides to maximize crop yield1,2.
      Neonicotinoids are the most widely used insecticides globally3, but increasing
      evidence of negative impacts on important pollinators4-9 and other non-target
      organisms10 has led to legislative reassessment and created demand for the
      development of alternative products. Sulfoximine-based insecticides are the most
      likely successor11, and are either licensed for use or under consideration for
      licensing in several worldwide markets3, including within the European Union12,
      where certain neonicotinoids (imidacloprid, clothianidin and thiamethoxam) are
      now banned from agricultural use outside of permanent greenhouse structures.
      There is an urgent need to pre-emptively evaluate the potential sub-lethal
      effects of sulfoximine-based pesticides on pollinators11, because such effects
      are rarely detected by standard ecotoxicological assessments, but can have major
      impacts at larger ecological scales13-15. Here we show that chronic exposure to
      the sulfoximine-based insecticide sulfoxaflor, at dosages consistent with
      potential post-spray field exposure, has severe sub-lethal effects on bumblebee
      (Bombus terrestris) colonies. Field-based colonies that were exposed to
      sulfoxaflor during the early growth phase produced significantly fewer workers
      than unexposed controls, and ultimately produced fewer reproductive offspring.
      Differences between the life-history trajectories of treated and control colonies
      first became apparent when individuals exposed as larvae began to emerge,
      suggesting that direct or indirect effects on a small cohort may have cumulative
      long-term consequences for colony fitness. Our results caution against the use of
      sulfoximines as a direct replacement for neonicotinoids. To avoid continuing
      cycles of novel pesticide release and removal, with concomitant impacts on the
      environment, a broad evidence base needs to be assessed prior to the development
      of policy and regulation.

PMID- 30111836
TI  - Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose.
AB  - Immune recognition of pathogen-associated molecular patterns (PAMPs) by pattern
      recognition receptors often activates proinflammatory NF-kappaB signalling1.
      Recent studies indicate that the bacterial metabolite D-glycero-beta-D-manno
      heptose 1,7-bisphosphate (HBP) can activate NF-kappaB signalling in host cytosol2
      4, but it is unclear whether HBP is a genuine PAMP and the cognate pattern
      recognition receptor has not been identified. Here we combined a transposon
      screen in Yersinia pseudotuberculosis with biochemical analyses and identified
      ADP-beta-D-manno-heptose (ADP-Hep), which mediates type III secretion system
      dependent NF-kappaB activation and cytokine expression. ADP-Hep, but not other
      heptose metabolites, could enter host cytosol to activate NF-kappaB. A CRISPR
      Cas9 screen showed that activation of NF-kappaB by ADP-Hep involves an ALPK1
      (alpha-kinase 1)-TIFA (TRAF-interacting protein with forkhead-associated domain)
      axis. ADP-Hep directly binds the N-terminal domain of ALPK1, stimulating its
      kinase domain to phosphorylate and activate TIFA. The crystal structure of the N
      terminal domain of ALPK1 and ADP-Hep in complex revealed the atomic mechanism of
      this ligand-receptor recognition process. HBP was transformed by host
      adenylyltransferases into ADP-heptose 7-P, which could activate ALPK1 to a lesser
      extent than ADP-Hep. ADP-Hep (but not HBP) alone or during bacterial infection
      induced Alpk1-dependent inflammation in mice. Our findings identify ALPK1 and ADP
      Hep as a pattern recognition receptor and an effective immunomodulator,
      respectively.

PMID- 30111838
TI  - Atomic iron and titanium in the atmosphere of the exoplanet KELT-9b.
AB  - To constrain the formation history of an exoplanet, we need to know its chemical
      composition1-3. With an equilibrium temperature of about 4,050 kelvin4, the
      exoplanet KELT-9b (also known as HD 195689b) is an archetype of the class of
      ultrahot Jupiters that straddle the transition between stars and gas-giant
      exoplanets and are therefore useful for studying atmospheric chemistry. At these
      high temperatures, iron and several other transition metals are not sequestered
      in molecules or cloud particles and exist solely in their atomic forms5. However,
      despite being the most abundant transition metal in nature, iron has not hitherto
      been detected directly in an exoplanet because it is highly refractory. The high
      temperatures of KELT-9b imply that its atmosphere is a tightly constrained
      chemical system that is expected to be nearly in chemical equilibrium5 and cloud
      free6,7, and it has been predicted that spectral lines of iron should be
      detectable in the visible range of wavelengths5. Here we report observations of
      neutral and singly ionized atomic iron (Fe and Fe+) and singly ionized atomic
      titanium (Ti+) in the atmosphere of KELT-9b. We identify these species using
      cross-correlation analysis8 of high-resolution spectra obtained as the exoplanet
      passed in front of its host star. Similar detections of metals in other ultrahot
      Jupiters will provide constraints for planetary formation theories.

PMID- 30111839
TI  - Cryo-EM structure of the insect olfactory receptor Orco.
AB  - The olfactory system must recognize and discriminate amongst an enormous variety
      of chemicals in the environment. To contend with such diversity, insects have
      evolved a family of odorant-gated ion channels comprised of a highly conserved co
      receptor (Orco) and a divergent odorant receptor (OR) that confers chemical
      specificity. Here, we present the single-particle cryo-electron microscopy
      structure of an Orco homomer from the parasitic fig wasp Apocrypta bakeri at 3.5
      A resolution, providing structural insight into this receptor family. Orco
      possesses a novel channel architecture, with four subunits symmetrically arranged
      around a central pore that diverges into four lateral conduits that open to the
      cytosol. The Orco tetramer has few inter-subunit interactions within the membrane
      and is bound together by a small cytoplasmic anchor domain. The minimal sequence
      conservation among ORs maps largely to the pore and anchor domain, shedding light
      on how the architecture of this receptor family accommodates its remarkable
      sequence diversity and facilitates the evolution of odour tuning.

PMID- 30111841
TI  - Modulating plant growth-metabolism coordination for sustainable agriculture.
AB  - Enhancing global food security by increasing the productivity of green revolution
      varieties of cereals risks increasing the collateral environmental damage
      produced by inorganic nitrogen fertilizers. Improvements in the efficiency of
      nitrogen use of crops are therefore essential; however, they require an in-depth
      understanding of the co-regulatory mechanisms that integrate growth, nitrogen
      assimilation and carbon fixation. Here we show that the balanced opposing
      activities and physical interactions of the rice GROWTH-REGULATING FACTOR 4
      (GRF4) transcription factor and the growth inhibitor DELLA confer homeostatic co
      regulation of growth and the metabolism of carbon and nitrogen. GRF4 promotes and
      integrates nitrogen assimilation, carbon fixation and growth, whereas DELLA
      inhibits these processes. As a consequence, the accumulation of DELLA that is
      characteristic of green revolution varieties confers not only yield-enhancing
      dwarfism, but also reduces the efficiency of nitrogen use. However, the nitrogen
      use efficiency of green revolution varieties and grain yield are increased by
      tipping the GRF4-DELLA balance towards increased GRF4 abundance. Modulation of
      plant growth and metabolic co-regulation thus enables novel breeding strategies
      for future sustainable food security and a new green revolution.

PMID- 30111840
TI  - Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing.
AB  - Common genetic contributions to autism spectrum disorder (ASD) reside in risk
      gene variants that individually have minimal effect sizes. As environmental
      factors that perturb neurodevelopment also underlie idiopathic ASD, it is crucial
      to identify altered regulators that can orchestrate multiple ASD risk genes
      during neurodevelopment. Cytoplasmic polyadenylation element binding proteins 1-4
      (CPEB1-4) regulate the translation of specific mRNAs by modulating their poly(A)
      tails and thereby participate in embryonic development and synaptic plasticity.
      Here we find that CPEB4 binds transcripts of most high-confidence ASD risk genes.
      The brains of individuals with idiopathic ASD show imbalances in CPEB4 transcript
      isoforms that result from decreased inclusion of a neuron-specific microexon. In
      addition, 9% of the transcriptome shows reduced poly(A)-tail length. Notably,
      this percentage is much higher for high-confidence ASD risk genes, correlating
      with reduced expression of the protein products of ASD risk genes. An equivalent
      imbalance in CPEB4 transcript isoforms in mice mimics the changes in mRNA
      polyadenylation and protein expression of ASD risk genes and induces ASD-like
      neuroanatomical, electrophysiological and behavioural phenotypes. Together, these
      data identify CPEB4 as a regulator of ASD risk genes.

PMID- 30111842
TI  - Restoration of vision after de novo genesis of rod photoreceptors in mammalian
      retinas.
AB  - In zebrafish, Muller glia (MG) are a source of retinal stem cells that can
      replenish damaged retinal neurons and restore vision1. In mammals, however, MG do
      not spontaneously re-enter the cell cycle to generate a population of stem or
      progenitor cells that differentiate into retinal neurons. Nevertheless, the
      regenerative machinery may exist in the mammalian retina, as retinal injury can
      stimulate MG proliferation followed by limited neurogenesis2-7. Therefore, there
      is still a fundamental question regarding whether MG-derived regeneration can be
      exploited to restore vision in mammalian retinas. Gene transfer of beta-catenin
      stimulates MG proliferation in the absence of injury in mouse retinas8. Here we
      report that following gene transfer of beta-catenin, cell-cycle-reactivated MG
      can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of
      transcription factors essential for rod cell fate specification and
      determination. MG-derived rods restored visual responses in Gnat1rd17Gnat2cpfl3
      double mutant mice, a model of congenital blindness9,10, throughout the visual
      pathway from the retina to the primary visual cortex. Together, our results
      provide evidence of vision restoration after de novo MG-derived genesis of rod
      photoreceptors in mammalian retinas.

PMID- 30111844
TI  - MicroRNA miR-34a downregulates FOXP1 during DNA damage response to limit BCR
      signalling in chronic lymphocytic leukaemia B cells.
AB  - The variable clinical course in chronic lymphocytic leukaemia (CLL) largely
      depends on p53 functionality and B-cell receptor (BCR) signalling propensity;
      however, it is unclear if there is any crosstalk between these pathways. We show
      that DNA damage response (DDR) activation leads to down-modulating the
      transcriptional factor FOXP1, which functions as a positive BCR signalling
      regulator and its high levels are associated with worse CLL prognosis. We
      identified microRNA (miRNA) miR-34a as the most prominently upregulated miRNA
      during DDR in CLL cells in vitro and in vivo during FCR therapy (fludarabine,
      cyclophosphamide, rituximab). MiR-34a induced by DDR activation and p53
      stabilization potently represses FOXP1 expression by binding in its 3'-UTR. The
      low FOXP1 levels limit BCR signalling partially via derepressing BCR-inhibitory
      molecule CD22. We also show that low miR-34a levels can be used as a biomarker
      for worse response or shorter progression free survival in CLL patients treated
      with FCR chemoimmunotherapy, and shorter overall survival, irrespective of TP53
      status. Additionally, we have developed a method for the absolute quantification
      of miR-34a copies and defined precise prognostic/predictive cutoffs. Overall,
      herein, we reveal for the first time that B cells limit their BCR signalling
      during DDR by down-modulating FOXP1 via DDR-p53/miR-34a axis.

PMID- 30111843
TI  - On the coordination of highly dynamic human movements: an extension of the
      Uncontrolled Manifold approach applied to precision jump in parkour.
AB  - The human body generally has more degrees of freedom than necessary for
      generating a given movement. According to the motor abundance principle, this
      redundancy is beneficial as it provides the central nervous system with
      flexibility and robustness for the generation of movements. Under the hypothesis
      of the Uncontrolled Manifold, the additional degrees of freedom are used to
      produce motor solutions by reducing the variability that affects the motion
      performance across repetitions. In this paper, we present a general mathematical
      framework derived from robotics to formulate kinematic and dynamic tasks in human
      movement. On this basis, an extension of the Uncontrolled Manifold approach is
      introduced to deal with dynamic movements. This extension allows us to present a
      complex experimental application of the proposed framework to highly dynamic task
      variables in parkour movements. This experiment involves dynamic tasks expressed
      in terms of linear and angular momenta. The results show that the central nervous
      system is able to coordinate such skilled tasks which appear to be preferentially
      controlled and hierarchically organized. The proposed extension is promising for
      the study of motion generation in anthropomorphic systems and provides a formal
      description to investigate kinematics and dynamics tasks in human motions.

PMID- 30111845
TI  - Simultaneous B and T cell acute lymphoblastic leukemias in zebrafish driven by
      transgenic MYC: implications for oncogenesis and lymphopoiesis.
AB  - Precursor-B cell acute lymphoblastic leukemia (pre-B ALL) is the most common
      pediatric cancer, but there are no useful zebrafish pre-B ALL models. We describe
      the first highly- penetrant zebrafish pre-B ALL, driven by human MYC. Leukemias
      express B lymphoblast-specific genes and are distinct from T cell ALL (T-ALL)
      which these fish also develop. Zebrafish pre-B ALL shares in vivo features and
      expression profiles with human pre-B ALL, and these profiles differ from
      zebrafish T-ALL or normal B and T cells. These animals also exhibit aberrant
      lymphocyte development. As the only robust zebrafish pre-B ALL model and only
      example where T-ALL also develops, this model can reveal differences between MYC
      driven pre-B vs. T-ALL and be exploited to discover novel pre-B ALL therapies.

PMID- 30111847
TI  - Examining the pathophysiology of short bowel syndrome and glucagon-like peptide 2
      analogue suitability in chronic intestinal failure: experience from a national
      intestinal failure unit.
AB  - INTRODUCTION: Short bowel syndrome (SBS) is a leading cause of intestinal failure
      (IF). Home parenteral nutrition (HPN) remains the standard treatment, with small
      intestinal transplantation reserved for cases with severe complications to HPN.
      There have recently been significant developments in growth factor therapy. We
      aimed to develop a greater contemporary understanding of our SBS-IF subset.
      METHOD: We performed a retrospective observational study of a prospectively
      maintained HPN audit database in October 2017. Intestinal anatomical details and
      parenteral requirements were recorded. Each case was assessed for eligibility for
      growth factor therapy using recently published trials. RESULTS: Of 273 patients
      receiving HPN, 152 (55.7%) had type three IF as a result of SBS (SBS-IF), with a
      mean duration of HPN of 61 months (range 4-416). Mean length of small intestine
      was 98 cm. Furthermore, 114 (41.8%) patients had an end jejunostomy (SBS-J), 18
      (6.6%) had an end ileostomy, and 7.3% of patients had all or part of the colon-in
      continuity. Crohn's disease was the most common underlying pathology. Univariate
      analysis for the whole HPN cohort demonstrated SBS-IF and a longer duration of
      HPN to be associated with higher PN energy requirements, p <= 0.0001. Of all, 73
      (48%) patients with SBS-IF were deemed suitable for GLP-2 analogue therapy, with
      co-morbidity being the most frequent cause of non-suitability (29.1%).
      CONCLUSION: We describe a large U.K. HPN cohort using ESPEN pathophysiological
      and clinical severity classification. The majority of patients with SBS-IF had a
      jejunostomy and relatively few had colon-in-continuity. Co-morbidity is the most
      common contra-indication to GLP-2 analogue therapy. CLINICAL RELEVANCY: GLP-2
      analogues are emerging as an important treatment for patients with short bowel
      syndrome. Our study explores patient suitability in a large HPN cohort managed in
      a national IF centre. Furthermore, the international variation in the
      pathophysiology of SBS-IF varies significantly, which can have a bearing on PN
      requirements and outcomes when GLP-2 analogues are used.

PMID- 30111848
TI  - Assessing the augmentation of Amblydromalus limonicus with the supplementation of
      pollen, thread, and substrates to combat greenhouse whitefly populations.
AB  - Due to issues with establishment and persistence of natural enemies in biological
      control, the provision of alternative food sources and oviposition sites are
      important factors to enhance pest control. In this study, three different
      supplementation treatments were examined for their ability to increase the
      populations of the predatory mite Amblydromalus limonicus, and its implications
      for greenhouse whitefly control on peppers and eggplants. These were: (1) pollen
      (Typha orientalis), (2) pollen and thread, (3) pollen, thread, and a substrate
      mixture of buckwheat, gorse, and rice husks, which were compared to a control
      treatment that had no supplementation. Significant treatment effects were found
      on pepper for A. limonicus (mite eggs p = 0.008, mobile mites p = <0.0001). The
      predatory mite successfully established and persisted at high population levels
      in the pollen-thread, and pollen-thread-substrate treatments. All supplementation
      treatments were able to control whitefly populations on peppers, while the
      control treatment failed to. The results obtained were formulated into possible
      application techniques for greenhouse growers to utilise.

PMID- 30111846
TI  - Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances
      response to chemotherapy.
AB  - Triple-negative breast cancer (TNBC) lacks targeted therapies and has a worse
      prognosis than other breast cancer subtypes, underscoring an urgent need for new
      therapeutic targets and strategies. IRE1 is an endoplasmic reticulum (ER) stress
      sensor, whose activation is predominantly linked to the resolution of ER stress
      and, in the case of severe stress, to cell death. Here we demonstrate that
      constitutive IRE1 RNase activity contributes to basal production of pro
      tumorigenic factors IL-6, IL-8, CXCL1, GM-CSF, and TGFbeta2 in TNBC cells. We
      further show that the chemotherapeutic drug, paclitaxel, enhances IRE1 RNase
      activity and this contributes to paclitaxel-mediated expansion of tumor
      initiating cells. In a xenograft mouse model of TNBC, inhibition of IRE1 RNase
      activity increases paclitaxel-mediated tumor suppression and delays tumor relapse
      post therapy. We therefore conclude that inclusion of IRE1 RNase inhibition in
      therapeutic strategies can enhance the effectiveness of current
      chemotherapeutics.

PMID- 30111849
TI  - Electrophysiological correlates of the interplay between low-level visual
      features and emotional content during word reading.
AB  - Processing affectively charged visual stimuli typically results in increased
      amplitude of specific event-related potential (ERP) components. Low-level
      features similarly modulate electrophysiological responses, with amplitude
      changes proportional to variations in stimulus size and contrast. However, it
      remains unclear whether emotion-related amplifications during visual word
      processing are necessarily intertwined with changes in specific low-level
      features or, instead, may act independently. In this pre-registered
      electrophysiological study, we varied font size and contrast of neutral and
      negative words while participants were monitoring their semantic content. We
      examined ERP responses associated with early sensory and attentional processes as
      well as later stages of stimulus processing. Results showed amplitude modulations
      by low-level visual features early on following stimulus onset - i.e., P1 and N1
      components -, while the LPP was independently modulated by these visual features.
      Independent effects of size and emotion were observed only at the level of the
      EPN. Here, larger EPN amplitudes for negative were observed only for small high
      contrast and large low contrast words. These results suggest that early increase
      in sensory processing at the EPN level for negative words is not automatic, but
      bound to specific combinations of low-level features, occurring presumably via
      attentional control processes.

PMID- 30111850
TI  - Identification of Urine Metabolites as Biomarkers of Early Lyme Disease.
AB  - Metabolites detectible in human biofluids are attractive biomarkers for the
      diagnosis of early Lyme disease (ELD), a vector-borne infectious disease. Urine
      represents an easily obtained clinical sample that can be applied for diagnostic
      purposes. However, few studies have explored urine for biomarkers of ELD. In this
      study, metabolomics approaches were applied to evaluate small molecule
      metabolites in urine from patients with ELD (n = 14), infectious mononucleosis (n
      = 14) and healthy controls (n = 14). Metabolic biosignatures for ELD versus
      healthy controls and ELD versus infectious mononucleosis were generated using
      untargeted metabolomics. Pathway analyses and metabolite identification revealed
      the dysregulation of several metabolic processes in ELD as compared to healthy
      controls or mononucleosis, including metabolism of tryptophan. Linear
      discriminant analyses demonstrated that individual metabolic biosignatures can
      correctly discriminate ELD from the other patient groups with accuracies of 71 to
      100%. These data provide proof-of-concept for use of urine metabolites as
      biomarkers for diagnostic classification of ELD.

PMID- 30111851
TI  - Characterization of avian influenza virus attachment patterns to human and pig
      tissues.
AB  - Wild birds of Anseriformes and Charadriiformes are natural reservoirs of
      influenza A viruses (IAVs). Occasionally, IAVs transmit and adapt to mammalian
      hosts, and are maintained as epidemic strains in their new hosts. Viral adaptions
      to mammalian hosts include altered receptor preference of host epithelial
      sialylated oligosaccharides from terminal alpha2,3-linked sialic acid (SA)
      towards alpha2,6-linked SA. However, alpha2,3-linked SA has been found in human
      respiratory tract epithelium, and human infections by avian IAVs (AIVs) have been
      reported. To further explore the attachment properties of AIVs, four AIVs of
      different subtypes were investigated on human and pig tissues using virus
      histochemistry. Additionally, glycan array analysis was performed for further
      characterization of IAVs' receptor structure tropism. Generally, AIV attachment
      was more abundant to human tissues than to pig tissues. The attachment pattern
      was very strong to human conjunctiva and upper respiratory tract, but variable to
      the lower respiratory tract. AIVs mainly attached to alpha2,3-linked SA, but also
      to combinations of alpha2,3- and alpha2,6-linked SA. The low attachment of these
      AIV isolates to pig tissues, but high attachment to human tissues, addresses the
      question whether AIVs in general require passage through pigs to obtain adaptions
      towards mammalian receptor structures.

PMID- 30111852
TI  - PP4397/FlgZ provides the link between PP2258 c-di-GMP signalling and altered
      motility in Pseudomonas putida.
AB  - Bacteria swim and swarm using rotating flagella that are driven by a membrane
      spanning motor complex. Performance of the flagella motility apparatus is
      modulated by the chemosensory signal transduction system to allow navigation
      through physico-chemical gradients - a process that can be fine-tuned by the
      bacterial second messenger c-di-GMP. We have previously analysed the Pseudomonas
      putida signalling protein PP2258 that has the capacity to both synthesize and
      degrade c-di-GMP. A PP2258 null mutant displays reduced motility, implicating the
      c-di-GMP signal originating from this protein in control of P. putida motility.
      In Escherichia coli and Salmonella, the PilZ-domain protein YcgR mediates c-di
      GMP responsive control of motility through interaction with the flagellar motors.
      Here we provide genetic evidence that the P. putida protein PP4397 (also known as
      FlgZ), despite low sequence homology and a different genomic context to YcgR,
      functions as a c-di-GMP responsive link between the signal arising from PP2258
      and alterations in swimming and swarming motility in P. putida.

PMID- 30111853
TI  - Simulating quantum dynamical phenomena using classical oscillators: Landau-Zener
      Stuckelberg-Majorana interferometry, latching modulation, and motional averaging.
AB  - A quantum system can be driven by either sinusoidal, rectangular, or noisy
      signals. In the literature, these regimes are referred to as Landau-Zener
      Stuckelberg-Majorana (LZSM) interferometry, latching modulation, and motional
      averaging, respectively. We demonstrate that these pronounced and interesting
      effects are also inherent in the dynamics of classical two-state systems. We
      discuss how such classical systems are realized using either mechanical,
      electrical, or optical resonators. In addition to the fundamental interest of
      such dynamical phenomena linking classical and quantum physics, we believe that
      these are attractive for the classical analogue simulation of quantum systems.

PMID- 30111855
TI  - An interesting cross-talk between the glucagon-like peptide-1 receptor axis and
      angiotensin receptor pathway for modulation of renal sodium handling in obesity.

PMID- 30111854
TI  - Cracking pattern of tissue slices induced by external extension provides useful
      diagnostic information.
AB  - Although biopsy is one of the most important methods for diagnosis in diseases,
      there is ambiguity based on the information obtained from the visual inspection
      of tissue slices. Here, we studied the effect of external extension on tissue
      slices from mouse liver with different stages of disease: Healthy normal state,
      Simple steatosis, Non-alcoholic steatohepatitis and Hepatocellular carcinoma. We
      found that the cracking pattern of a tissue slice caused by extension can provide
      useful information for distinguishing among the disease states. Interestingly,
      slices with Hepatocellular carcinoma showed a fine roughening on the cracking
      pattern with a characteristic length of the size of cells, which is much
      different than the cracking pattern for slices with non-cancerous steatosis, for
      which the cracks were relatively straight. The significant difference in the
      cracking pattern depending on the disease state is attributable to a difference
      in the strength of cell-cell adhesion, which would be very weak under carcinosis.
      As it is well known that the manner of cell-cell adhesion neatly concerns with
      the symptoms in many diseases, it may be promising to apply the proposed
      methodology to the diagnosis of other diseases.

PMID- 30111856
TI  - Vasorelaxant effect of sinensetin via the NO/sGC/cGMP pathway and potassium and
      calcium channels.
AB  - Orthosiphon stamineus Benth. (Lambiaceae) is an important traditional plant for
      the treatment of hypertension. Previous studies have demonstrated that the
      sinensetin content in O. stamineus is correlated with its vasorelaxant activity.
      However, there is still very little information regarding the vasorelaxant effect
      of sinensetin due to a lack of scientific studies. Therefore, the present study
      was designed to investigate the underlying mechanism of action of sinensetin in
      vasorelaxation using an in vitro precontraction aortic ring assay. The changes in
      the tension of the aortic ring preparations were recorded using a force
      displacement transducer and the PowerLab system. The mechanisms of the
      vasorelaxant effect of sinensetin were determined in the presence of antagonists.
      Sinensetin caused relaxation of the aortic ring precontracted with PE in the
      presence and absence of the endothelium and with potassium chloride in
      endothelium-intact aortic rings. In the presence of Nomega-nitro-L-arginine
      methyl ester (nitric oxide synthase inhibitor), methylene blue (cyclic guanosine
      monophosphate lowering agent), ODQ (selective soluble guanylate cyclase
      inhibitor), indomethacin (a nonselective cyclooxygenase inhibitor),
      tetraethylammonium (nonselective calcium activator K+ channel blocker), 4
      aminopyridine (voltage-dependent K+ channel blocker), barium chloride (inwardly
      rectifying Kir channel blocker), glibenclamide (nonspecific ATP-sensitive K+
      channel blocker), atropine (muscarinic receptor blocker), or propranolol (beta
      adrenergic receptor blocker), the relaxation stimulated by sinensetin was
      significantly reduced. Sinensetin was also active in reducing Ca2+ release from
      the sarcoplasmic reticulum (via IP3R) and in blocking calcium channels (VOCC).
      The present study demonstrates the vasorelaxant effect of sinensetin, which
      involves the NO/sGC/cGMP and indomethacin pathways, calcium and potassium
      channels, and muscarinic and beta-adrenergic receptors.

PMID- 30111858
TI  - Expression analysis and functional characterization of the mouse cysteine-rich
      with EGF-like domains 2.
AB  - We have previously identified a novel endoplasmic reticulum (ER) stress-inducible
      protein, namely, cysteine-rich with EGF-like domains 2 (CRELD2), which is
      predominantly regulated by ATF6. However, few studies on intrinsic CRELD2 have
      been published. In the present study, we elucidated the expression of intrinsic
      CRELD2 in mouse tissues and ER stress- treated Neuro2a cells. Among nine tissues
      we tested, CRELD2 protein in the heart and skeletal muscles was negligible.
      CRELD2 expression in Neuro2a cells was induced at the late phase after treatment
      with tunicamycin (Tm) compared with rapid induction of growth arrest and DNA
      damage inducible gene 153 (GADD153). On the other hand, another ER stress
      inducer, thapsigargin, increased the intrinsic CRELD2 secretion from Neuro2a
      cells. We furthermore established CRELD2-deficient Neuro2a cells to evaluate
      their features. In combination with the NanoLuc complementary reporter system,
      which was designed to detect protein-protein interaction in living cells, CRELD2
      interacted with not only CRELD2 itself but also with ER localizing proteins in
      Neuro2a cells. Finally, we investigated the responsiveness of CRELD2-deficient
      cells against Tm-treatment and found that CRELD2 deficiency did not affect the
      expression of genes triggered by three canonical ER stress sensors but rendered
      Neuro2a cells vulnerable to Tm-stimulation. Taken together, these findings
      provide the novel molecular features of CRELD2, and its further characterization
      would give new insights into understanding the ER homeostasis and ER stress
      induced cellular dysfunctions.

PMID- 30111857
TI  - COPD is accompanied by co-ordinated transcriptional perturbation in the
      quadriceps affecting the mitochondria and extracellular matrix.
AB  - Skeletal muscle dysfunction is a frequent extra-pulmonary manifestation of
      Chronic Obstructive Pulmonary Disease (COPD) with implications for both quality
      of life and survival. The underlying biology nevertheless remains poorly
      understood. We measured global gene transcription in the quadriceps using
      Affymetrix HuGene1.1ST arrays in an unselected cohort of 79 stable COPD patients
      in secondary care and 16 healthy age- and gender-matched controls. We detected
      1,826 transcripts showing COPD-related variation. Eighteen exhibited >=2fold
      changes (SLC22A3, FAM184B, CDKN1A, FST, LINC01405, MUSK, PANX1, ANKRD1, C12orf75,
      MYH1, POSTN, FRZB, TNC, ACTC1, LINC00310, MYH3, MYBPH and AREG). Thirty-one
      transcripts possessed previous reported evidence of involvement in COPD through
      genome-wide association, including FAM13A. Network analysis revealed a
      substructure comprising 6 modules of co-expressed genes. We identified modules
      with mitochondrial and extracellular matrix features, of which IDH2, a central
      component of the mitochondrial antioxidant pathway, and ABI3BP, a proposed switch
      between proliferation and differentiation, represent hubs respectively. COPD is
      accompanied by coordinated patterns of transcription in the quadriceps involving
      the mitochondria and extracellular matrix and including genes previously
      implicated in primary disease processes.

PMID- 30111859
TI  - Three-stage processing of category and variation information by entangled
      interactive mechanisms of peri-occipital and peri-frontal cortices.
AB  - Object recognition has been a central question in human vision research. The
      general consensus is that the ventral and dorsal visual streams are the major
      processing pathways undertaking objects' category and variation processing. This
      overlooks mounting evidence supporting the role of peri-frontal areas in category
      processing. Yet, many aspects of visual processing in peri-frontal areas have
      remained unattended including whether these areas play role only during active
      recognition and whether they interact with lower visual areas or process
      information independently. To address these questions, subjects were presented
      with a set of variation-controlled object images while their EEG were recorded.
      Considerable amounts of category and variation information were decodable from
      occipital, parietal, temporal and prefrontal electrodes. Using information
      selectivity indices, phase and Granger causality analyses, three processing
      stages were identified showing distinct directions of information transaction
      between peri-frontal and peri-occipital areas suggesting their parallel yet
      interactive role in visual processing. A brain-plausible model supported the
      possibility of interactive mechanisms in peri-occipital and peri-frontal areas.
      These findings, while promoting the role of prefrontal areas in object
      recognition, extend their contributions from active recognition, in which peri
      frontal to peri-occipital pathways are activated by higher cognitive processes,
      to the general sensory-driven object and variation processing.

PMID- 30111861
TI  - Detecting the Causal Effect of Soil Moisture on Precipitation Using Convergent
      Cross Mapping.
AB  - As a vital land surface parameter, soil moisture influences climate through its
      impact on water and energy cycles. However, the effect of soil moisture on
      precipitation has been strongly debated. In this study, a new causal detection
      method, convergent cross mapping (CCM), was applied to explore the causality
      between soil moisture and precipitation over low- and mid- latitude regions in
      the Northern Hemisphere. CCM method generally identified a strong effect of soil
      moisture on precipitation. Specifically, the optimal effect of soil moisture on
      precipitation occurred with a lag of one month and clearly decreased after four
      months, suggesting that soil moisture has potentials to improve the accuracy of
      precipitation forecast at a sub-seasonal scale. In addition, as climate (i.e.,
      aridity index) changed from dry to wet, the effect of soil moisture on
      precipitation first increased and then decreased with peaks in semi-arid and semi
      humid areas. These findings statistically support the hypothesis that soil
      moisture impacts precipitation and also provide a reference for the design of
      climate prediction systems.

PMID- 30111860
TI  - Elevated expression of pancreatic adenocarcinoma upregulated factor (PAUF) is
      associated with poor prognosis and chemoresistance in epithelial ovarian cancer.
AB  - Pancreatic adenocarcinoma upregulated factor (PAUF) is a ligand of toll-like
      receptors (TLRs) and has been reported to be involved in pancreatic tumor
      development. However, the significance of PAUF expression in epithelial ovarian
      cancer remains unclear. We aimed to investigate the possible clinical
      significance of PAUF in epithelial ovarian cancer. We examined the link between
      PAUF and TLR4 in ovarian cancer cell lines. Recombinant PAUF induced cell
      activation and proliferation in ovarian cancer cell lines, whereas PAUF knockdown
      inhibited these properties. Subsequently, we assessed PAUF and TLR4 expression by
      immunohistochemistry on tissue microarray of 408 ovarian samples ranging from
      normal to metastatic. PAUF expression positively correlated with TLR4 expression.
      Overexpression of PAUF was associated with high-grade tumor (p = 0.014) and
      chemoresistant tumor (p = 0.017). Similarly, high expression of TLR4 correlated
      with advanced tumor stage (p = 0.002) and chemoresistant tumor (p = 0.001).
      Multivariate analysis indicated that PAUFhigh, TLR4high, and PAUFhigh/TLR4high
      expression are independent prognostic factor for progression-free survival, while
      TLR4high and PAUFhigh/TLR4high expression were independent prognostic factors for
      overall survival. Our results suggest that PAUF has a role in ovarian cancer
      progression and is a potential prognostic marker and novel chemotherapeutic
      target for ovarian cancer.

PMID- 30111862
TI  - Potent Antitumor Effects of a Combination of Three Nutraceutical Compounds.
AB  - Head and neck squamous cell carcinoma (HNSCC) is associated with low survival,
      and the current aggressive therapies result in high morbidity. Nutraceuticals are
      dietary compounds with few side effects. However, limited antitumor efficacy has
      restricted their application for cancer therapy. Here, we examine combining
      nutraceuticals, establishing a combination therapy that is more potent than any
      singular component, and delineate the mechanism of action. Three formulations
      were tested: GZ17-S (combined plant extracts from Arum palaestinum, Peganum
      harmala and Curcuma longa); GZ17-05.00 (16 synthetic components of GZ17-S); and
      GZ17-6.02 (3 synthetic components of GZ17S; curcumin, harmine and isovanillin).
      We tested the formulations on HNSCC proliferation, migration, invasion,
      angiogenesis, macrophage viability and infiltration into the tumor and tumor
      apoptosis. GZ17-6.02, the most effective formulation, significantly reduced in
      vitro assessments of HNSCC progression. When combined with cisplatin, GZ17-6.02
      enhanced anti-proliferative effects. Molecular signaling cascades inhibited by
      GZ17-6.02 include EGFR, ERK1/2, and AKT, and molecular docking analyses
      demonstrate GZ17-6.02 components bind at distinct binding sites. GZ17-6.02
      significantly inhibited growth of HNSCC cell line, patient-derived xenografts,
      and murine syngeneic tumors in vivo (P < 0.001). We demonstrate GZ17-6.02 as a
      highly effective plant extract combination and pave the way for future clinical
      application in HNSCC.

PMID- 30111863
TI  - High-dimensional immune phenotyping and transcriptional analyses reveal robust
      recovery of viable human immune and epithelial cells from frozen gastrointestinal
      tissue.
AB  - Simultaneous analyses of peripheral and mucosal immune compartments can yield
      insight into the pathogenesis of mucosal-associated diseases. Although methods to
      preserve peripheral immune cells are well established, studies involving mucosal
      immune cells have been hampered by lack of simple storage techniques. We provide
      a cryopreservation protocol allowing for storage of gastrointestinal (GI) tissue
      with preservation of viability and functionality of both immune and epithelial
      cells. These methods will facilitate translational studies allowing for batch
      analysis of mucosal tissue to investigate disease pathogenesis, biomarker
      discovery and treatment responsiveness.

PMID- 30111864
TI  - Young species of cupuladriid bryozoans occupied new Caribbean habitats faster
      than old species.
AB  - The breadth of habitat occupied by a species, and the rate at which a species can
      expand into new habitats has important ecological and evolutionary consequences.
      Here we explore when extant species of free-living cupuladriid bryozoans expanded
      into new benthic Caribbean habitats that emerged during the final stages of
      formation of the Isthmus of Panama. Habitat breadth was estimated using the
      abundances of over 90,000 colonies in ten cupuladriid species, along with the
      ecological and sedimentary characteristics of the samples in which they occurred.
      Data reveal that all species expanded their habitat breadths during the last 6
      Myr, but did so at a different tempo. 'Young' species - those that originated
      after 5 Ma - expanded relatively quickly, whereas 'old' species - those that
      originated before 9 Ma - took a further 2 Myr to achieve a comparable level of
      expansion. We propose that, like invasive species, young species are less
      restrained when expanding their habitat breadths compared to older well
      established species. Understanding the mechanism causing this restraint requires
      further research.

PMID- 30111865
TI  - Multiplex mutagenesis of four clustered CrRLK1L with CRISPR/Cas9 exposes their
      growth regulatory roles in response to metal ions.
AB  - Resolving functions of closely linked genes is challenging or nearly impossible
      with classical genetic tools. Four members of the Catharanthus roseus receptor
      like kinase 1-like (CrRLK1L) family are clustered on Arabidopsis chromosome five.
      To resolve the potentially redundant functions of this subclass of CrRLK1Ls named
      MEDOS1 to 4 (MDS1 to 4), we generated a single CRISPR/Cas9 transformation vector
      using a Golden Gate based cloning system to target all four genes simultaneously.
      We introduce single mutations within and deletions between MDS genes as well as
      knock-outs of the whole 11 kb gene cluster. The large MDS cluster deletion was
      inherited in up to 25% of plants lacking the CRISPR/Cas9 construct in the T2
      generation. In contrast to described phenotypes of already characterized CrRLK1L
      mutants, quadruple mds knock-outs were fully fertile, developed normal root hairs
      and trichomes and responded to pharmacological inhibition of cellulose
      biosynthesis similar to wildtype. Recently, we demonstrated the role of four
      CrRLK1L in growth adaptation to metal ion stress. Here we show the involvement of
      MDS genes in response to Ni2+ during hypocotyl elongation and to Cd2+ and Zn2+
      during root growth. Our finding supports the model of an organ specific network
      of positively and negatively acting CrRLK1Ls.

PMID- 30111866
TI  - Stimulation of carbon nanomaterials on syntrophic oxidation of butyrate in
      sediment enrichments and a defined coculture.
AB  - It remains elusive if direct interspecies electron transfer (DIET) occurs in
      canonical syntrophy involving short-chain fatty acids oxidation. In the present
      study, we determined the effects of carbon nanomaterials on syntrophic oxidation
      of butyrate in two lake sediment enrichments and a defined coculture comprising
      Syntrophomonas wolfei and Methanococcus Maripaludis. After four continuous
      transfers of enrichment cultivation, Syntrophomonas dominated the bacterial
      populations in enrichments, and the dominated methanogens comprised
      Methanosarcina and Methanospirillum in one enrichment (from Weiming Lake) and
      Methanoregula and Methanospirillum in another (from Erhai Lake). Butyrate
      oxidation and CH4 production was significantly accelerated by carbon nanotubes
      (CNTs) in both enrichments. Replacement of CNTs by magnetite caused similar
      stimulating effect. For the defined coculture, two carbon nanomaterials, CNTs and
      reduced graphene oxide (rGO), were tested, both showed consistently stimulating
      effects on butyrate oxidation. Addition of kaolinite, an electric nonconductive
      clay mineral, however, revealed no effect. The test on M. maripaludis in pure
      culture showed no effect by rGO and a negative effect by CNTs (especially at a
      high concentration). Fluorescence in situ hybridization (FISH) and scanning
      electron microscopy (SEM) revealed that microbial cells were interwoven by CNTs
      forming cell-CNT mixture aggregates, and in case of rGO, cells were attached to
      surface or wrapped-up by rGO thin sheets. Collectively, our data suggest that the
      presence of conductive nanomaterials likely induces DIET in syntrophic butyrate
      oxidation.

PMID- 30111867
TI  - Effect of medication adherence on long-term all-cause-mortality and
      hospitalization for cardiovascular disease in 65,067 newly diagnosed type 2
      diabetes patients.
AB  - This study determined the effects of anti-diabetic medication adherence on the
      long-term all-cause mortality and hospitalization for cerebrovascular disease and
      myocardial infarction among newly diagnosed patients. The study used
      retrospective cohort from the National Health Insurance Service. Study
      participants were 65,076 newly diagnosed type 2 diabetes mellitus patients aged
      >=40 years. The medication adherence was evaluated from the proportion of days
      covered (PDC) between 2006 and 2007. Outcome variables were mortality, newly
      diagnosed cerebrovascular disease (CVD) and myocardial infarction (MI) in 2008
      2017. Cox-proportional hazard regression analysis was performed. After adjusting
      for sex, age, monthly contribution, insurance type, medical institution type,
      Charlson comorbidity index score, disability, hypertension, and active
      ingredients of oral hypoglycemic agents, the adjusted hazard ratio (aHR) for all
      cause-mortality of the lowest PDC group (<0.20) was 1.45 (95% confidence interval
      [CI] = 1.36-1.54) as compared to the highest PDC (>=0.8). The aHR for all-cause
      mortality associated with PDC levels of 0.60-0.79, 0.40-0.59, and 0.20-0.39 were
      1.19, 1.26, and 1.34, respectively (Ptrend < 0.001). Compared to the highest PDC
      group, diabetic patients with the lowest PDC had elevated risk for CVD (aHR =
      1.41; 95% CI = 1.30-1.52; Ptrend < 0.001). Improving anti-diabetic medication
      adherence among newly diagnosed type 2 diabetes mellitus patients is essential to
      the reduce risk for cardiovascular disease and long-term all-cause mortality.

PMID- 30111868
TI  - Polysaccharide utilization loci of North Sea Flavobacteriia as basis for using
      SusC/D-protein expression for predicting major phytoplankton glycans.
AB  - Marine algae convert a substantial fraction of fixed carbon dioxide into various
      polysaccharides. Flavobacteriia that are specialized on algal polysaccharide
      degradation feature genomic clusters termed polysaccharide utilization loci
      (PULs). As knowledge on extant PUL diversity is sparse, we sequenced the genomes
      of 53 North Sea Flavobacteriia and obtained 400 PULs. Bioinformatic PUL
      annotations suggest usage of a large array of polysaccharides, including
      laminarin, alpha-glucans, and alginate as well as mannose-, fucose-, and xylose
      rich substrates. Many of the PULs exhibit new genetic architectures and suggest
      substrates rarely described for marine environments. The isolates' PUL
      repertoires often differed considerably within genera, corroborating ecological
      niche-associated glycan partitioning. Polysaccharide uptake in Flavobacteriia is
      mediated by SusCD-like transporter complexes. Respective protein trees revealed
      clustering according to polysaccharide specificities predicted by PUL
      annotations. Using the trees, we analyzed expression of SusC/D homologs in
      multiyear phytoplankton bloom-associated metaproteomes and found indications for
      profound changes in microbial utilization of laminarin, alpha-glucans, beta
      mannan, and sulfated xylan. We hence suggest the suitability of SusC/D-like
      transporter protein expression within heterotrophic bacteria as a proxy for the
      temporal utilization of discrete polysaccharides.

PMID- 30111870
TI  - Cigarette smoking and thyroid cancer risk: a cohort study.
AB  - BACKGROUND: We evaluated the association between smoking status and thyroid
      cancer risk and whether this association is mediated by body mass index (BMI) and
      thyroid-stimulating hormone (TSH). METHODS: We performed a cohort study of 96,855
      Korean adults who were followed annually or biennially for a median of 5.9 years.
      RESULTS: During 511,052.9 person-years of follow-up, 1,250 participants developed
      thyroid cancer. In men, we observed a dose-dependent inverse association between
      current smoking, pack-years, and thyroid cancer. After adjustment for
      confounders, adjusted hazard ratios (95% confidence intervals) for thyroid cancer
      comparing current and former smokers to never smokers were 0.58 (0.45-0.75) and
      0.93 (0.73-1.18), respectively. After further adjustment for BMI and TSH as
      potential mediators, this association was slightly attenuated, but remained
      significant. For women, current smokers tended to have a lower risk of thyroid
      cancer, but this association did not reach statistical significance. CONCLUSIONS:
      In this cohort study, current smoking was associated with a decreased risk of
      incident thyroid cancer in men but not in women and this association was observed
      even after adjusting for TSH and BMI levels as potential mediators. Further
      mechanistic studies are needed to elucidate the possible effect of smoking on the
      pathogenesis of thyroid cancer development.

PMID- 30111869
TI  - Flt3 ligand treatment reduces enterovirus A71 lethality in mice with enhanced B
      cell responses.
AB  - Enterovirus A71 (EV-A71) infection can induce encephalitis, which causes death or
      long-term neurological sequelae, especially in young children. Using a murine
      infection model, we searched for anti-EV-A71 agents, because effective therapies
      are not available to control fatal infection. In EV-A71-infected mice, treatment
      with the hematopoietic growth factor, Fms-like tyrosine-kinase 3 ligand (Flt3
      ligand) before infection reduced the lethality and tissue viral loads. Flt3
      ligand failed to enhance the production of type I interferons. Instead, Flt3
      ligand boosted the numbers of dendritic cells and, particularly lymphocytes in
      infected organs with an expansion of spleen B cells, and resulted in an increased
      titer of virus-specific antibody with neutralizing activity in the serum. The
      protective effect of Flt3 ligand was abolished in B cell-deficient mice. Our
      findings revealed that Flt3 ligand administration promotes resistance to EV-A71
      infection with enhanced B cell response in a mechanism rarely reported before.

PMID- 30111871
TI  - BRCA1 and BRCA2 mRNA-expression prove to be of clinical impact in ovarian cancer.
AB  - BACKGROUND: Mutations in BRCA1 and BRCA2 are associated with better survival in
      ovarian cancer (OC) patients due to a better response to platinum-based
      chemotherapy. However, the impact of the BRCA1/2 mRNA-expression is not well
      characterized in OC. PATIENTS AND METHODS: We investigated BRCA1/2 mRNA
      expression in 12 non-neoplastic fallopian tubes and 201 epithelial OCs in
      relation to their clinical characteristics. RESULTS: We found higher BRCA1/2 mRNA
      expression in OCs compared to controls (P = 0.011, P < 0.001, respectively).
      BRCA1 mutated OCs exhibited lower BRCA1 (P = 0.014) but higher BRCA2 mRNA
      expression (P = 0.001). Low BRCA1-expression was associated with favorable
      overall survival (OS) (P = 0.012) and low BRCA2-expression with better
      progression-free survival (PFS) and OS (P = 0.004, P = 0.001, respectively). A
      subgroup-analysis showed that this effect was confined only to the BRCA1-wildtype
      cancers. Cox-regression confirmed the prognostic significance of BRCA1-expression
      for OS (P = 0.028). Independency of the prognostic value of BRCA2-expression for
      PFS (P = 0.045) and OS (P = 0.015) was restricted to high-grade serous OCs. Fully
      platinum-sensitivity was characterized by lower BRCA1/2 mRNA-expression in BRCA1
      wildtype cancers in comparison to platinum-refractory OC. CONCLUSION: Our
      findings may reflect higher platinum-sensitivity due to reduced capacity of DNA
      damage repair in tissues with low BRCA1/2-expression. In this context, especially
      in BRCA-wildtype cancers both parameters could also be potential predictors for
      PARP-sensitivity.

PMID- 30111872
TI  - Author Correction: Retrieval induces adaptive forgetting of competing memories
      via cortical pattern suppression.
AB  - In the published version of this article, a detail is missing from the Methods
      section "Experimental procedure." The following sentence is to be inserted at the
      end of its fourth paragraph: "If participants failed to respond within 3.5 s, we
      assumed that they were unable to successfully recognize the item and coded the
      corresponding trial as an error." The critical behavioral forgetting effect is
      significant irrespective of whether these timeouts are coded as errors (t23 =
      4.91, P < 0.001) or as missing data (t23 = 3.31, P < 0.01). The original article
      has not been corrected.

PMID- 30111873
TI  - Poly(dA:dT) make it and break it.

PMID- 30111874
TI  - Author Correction: Functional 5' UTR mRNA structures in eukaryotic translation
      regulation and how to find them.
AB  - The legend of Figure 1 has been modified to remove misleading referencing to
      evolution. The title of the legend has been modified from 'Evolutionary expansion
      of eukaryotic 5' UTR lengths' to 'Interspecies variation in 5' UTR lengths'; the
      first sentence of the legend has been modified from 'The length of 5'
      untranslated regions (UTRs) has increased in eukaryotes during evolution...' to
      'The length of 5' untranslated regions (UTRs) varies in eukaryotes...'. The
      changes have been made in the HTML and PDF versions of the manuscript.

PMID- 30111875
TI  - Author Correction: Sphingolipids and their metabolism in physiology and disease.
AB  - In the original Figure 2, sphingolipids on the endosomal and lysosomal membranes
      are facing the outside of these organelles. The correct orientation of these
      species should be towards the lumen, as shown in the corrected figure.

PMID- 30111877
TI  - A wet-filtration-zipping approach for fabricating highly electroconductive and
      auxetic graphene/carbon nanotube hybrid buckypaper.
AB  - A combination of carbon nanotubes (CNT) and graphene in the form of macroscopic
      hybrid buckypaper (HBP), exhibits a unique set of properties that can be
      exploited for many emerging applications. Here, we present a simple, inexpensive
      and scalable approach for the synthesis of highly conductive auxetic graphene/CNT
      HBP via wet-filtration-zipping and demonstrate the electrical, electrochemical
      and mechanical performance (tensile, mode I and mode III fracture) of synthesized
      HBP. An overall increase in electrical conductivity of 247% is observed for HBP
      (50 wt.% graphene and 50 wt.% CNT) as compared to BP (100 wt.% CNT) due to
      effective electronic percolation through the graphene and CNT. As a negative
      electrode for lithium-ion batteries, HBP shows 50% higher gravimetric specific
      capacity and 89% lower charge transfer resistance relative to BP. The graphene
      content in the HBP influences the mechanical performance providing an auxetic
      structure to HBP with large negative Poisson's ratio. The facile green-chemistry
      approach reported here can be readily applied to any other 1D and 2D materials
      and solves key challenges associated with existing buckypaper manufacturing
      methods. The potential of the synthesis method to integrate with current
      cellulose paper manufacturing technology and its scalability demonstrate the
      novelty of the work for industrial scale production.

PMID- 30111876
TI  - Opioids prevent regeneration in adult mammals through inhibition of ROS
      production.
AB  - Inhibition of regeneration and induction of tissue fibrosis are classic outcomes
      of tissue repair in adult mammals. Here, using a newly developed model of
      regeneration in adult mammals i.e. regeneration after massive resection of an
      inguinal fat pad, we demonstrate that both endogenous and exogenous opioids
      prevent tissue regeneration in adults, by inhibiting the early production of
      reactive oxygen species (ROS) that generally occurs after lesion and is required
      for regeneration. These effects can be overcome and regeneration induced by the
      use of an opioid antagonist. The results obtained in both our new model and the
      gold standard adult zebrafish demonstrate that this mechanism can be considered
      as a general paradigm in vertebrates. This work clearly demonstrates that ROS is
      required for tissue regeneration in adult mammals and shows the deleterious
      effect of opioids on tissue regeneration through the control of this ROS
      production. It thus raises questions about opioid-based analgesia in
      perioperative care.

PMID- 30111878
TI  - Light-programmable manipulation of DC field in Laplacian Meta-devices.
AB  - Impressive progresses have been achieved in the field of metamaterial to mimic
      the illusion or camouflage effects in nature. These include invisible cloaks and
      many other cloak-based illusion meta-devices. However, to date many experiments
      only present single, static or discretized functionalities. The dynamical control
      of multiple kinds of illusion signals can only be achieved by embedding complex
      active sources directly connected to external stimuli, leading to limited on/off
      switching effect in a contact fashion. Here, we experimentally demonstrate a
      distinct scheme to incorporate multi-functions into one passive Laplacian DC meta
      device, assisted by light illumination. It is shown that light-programmable
      cloaking, full illusion, and partial illusion can be achieved on the same device
      without physical contact of the heating pads or electric bias, at the cost of
      only four kinds of natural bulk materials with homogeneous parameters throughout.
      A DC network is fabricated to demonstrate the proof of concept, with measurement
      results in good agreement with the numerical simulations. The proposed scheme may
      open a new avenue to the non-contact multiphysical control of multi-illusion
      functions for Laplacian fields.

PMID- 30111879
TI  - Urea influences amino acid turnover in bovine cumulus-oocyte complexes, cumulus
      cells and denuded oocytes, and affects in vitro fertilization outcome.
AB  - High-protein diets often lead to an increase in urea concentration in follicular
      fluid of dairy cows, which may reduce oocyte competence. In the present study,
      maturation media were supplemented with urea (0, 20, 40 mg/dl), and amino acids
      (AAs) turnover was evaluated in the 24-h spent media of specimens (cell types),
      bovine cumulus-oocyte complexes (COCs), cumulus cells (CCs), or denuded oocytes
      (DOs). The main effects of urea and cell type, and their interaction were
      significant on the individual turnover (expect threonine, glycine, and tyrosine)
      and total turnover, depletion, and appearance of AAs. The results showed a high
      level of urea and DOs increased the depletion of all AAs and that of essential
      and non-AAs, respectively. Sensitivity analysis revealed the highest sensitivity
      of isoleucine, lysine, and tryptophan to urea, especially in DOs. Principal
      component analysis (PCA) evaluated the strong correlations between the turnover
      of: (1) glutamine, aspartic acid or glycine, and developmental competence and
      fertilization of COCs; (2) serine, isoleucine, valine or glutamic acid, and
      cleavage rate of DOs; and (3) serine, glutamine, aspartic acid or alanine, and
      CCs viability. In conclusion, urea significantly changed the turnover of AAs by
      COCs, CCs and DOs, and reduced the subsequent developmental competence of bovine
      oocytes.

PMID- 30111880
TI  - Resistive switching in nano-structures.
AB  - Solid state memory and switching devices aimed at replacing the flash memory
      technology operate by switching from the high to low resistance when conductive
      filaments are created in response to the electric pulse. The filaments are
      identified with either structurally different protrusions or purely electronic
      conductive pathways. The former can appear via the field induced nucleation
      (FIN), while the latter do not require phase transformations and are attributed
      to certain types of temperature and bias dependent conductivity. The existing
      understanding of those processes ignores features related to extremely small
      linear sizes of nano-structures. Such are, for example, the device sizes smaller
      than critical nucleation radii, and/or the electron energy relaxation lengths
      exceeding the structure dimensions. This paper develops a theory of switching
      under nano-size conditions. We show how the structure thinness can make FIN a
      truly threshold phenomenon possible only for voltage (not the field) exceeding a
      certain critical value. We predict the possibility of threshold switching without
      memory for certain thickness dependent voltages. The thermal runaway mechanism of
      electronic switching is described analytically leading to results consistent with
      the published numerical modeling. Our predictions offer possible experimental
      verifications deciding between FIN and thermal runaway switching.

PMID- 30111881
TI  - Contribution of RAD51D germline mutations in breast and ovarian cancer in Greece.
AB  - RAD51D gene's protein product is known to be involved in the DNA repair mechanism
      by homologous recombination. RAD51D germline mutations have been recently
      associated with ovarian and breast cancer (OC and BC, respectively)
      predisposition. Our aim was to evaluate the frequency of hereditary RAD51D
      mutations in Greek patients. To address this, we have screened for RAD51D
      germline mutations 609 BRCA1- and BRCA2-negative patients diagnosed with OC,
      unselected for age or family history, and 569 BC patients diagnosed under 55
      years and with an additional relative with BC or OC. We identified four
      pathogenic mutations in four unrelated individuals with family history of BC
      and/or OC. Three of the RAD51D carriers had developed BC, while the other one was
      an OC patient, thus accounting for a mutation frequency of 0.16% in the OC cohort
      and 0.53% in the BC cohort. One of the detected mutations is novel (c.738 + 1G >
      A), whereas the rest had been detected previously (p.Gln151Ter, p.Arg186Ter, and
      p.Arg300Ter). It is noteworthy that the 4 carrier families had 13 BC cases and
      only 4 OC cases. Our data support that RAD51D should be implemented into the
      comprehensive multigene panel, as mutation carriers may benefit from the
      administration of PARP inhibitors.

PMID- 30111882
TI  - Genetic diversity maintained among fragmented populations of a tree undergoing
      range contraction.
AB  - Dwarf birch (Betula nana) has a widespread boreal distribution but has declined
      significantly in Britain where populations are now highly fragmented. We analyzed
      the genetic diversity of these fragmented populations using markers that differ
      in mutation rate: conventional microsatellites markers (PCR-SSRs), RADseq
      generated transition and transversion SNPs (RAD-SNPs), and microsatellite markers
      mined from RADseq reads (RAD-SSRs). We estimated the current population sizes by
      census and indirectly, from the linkage-disequilibrium found in the genetic
      surveys. The two types of estimate were highly correlated. Overall, we found
      genetic diversity to be only slightly lower in Britain than across a comparable
      area in Scandinavia where populations are large and continuous. While the
      ensemble of British fragments maintain diversity levels close to Scandinavian
      populations, individually they have drifted apart and lost diversity;
      particularly the smaller populations. An ABC analysis, based on coalescent
      models, favors demographic scenarios in which Britain maintained high levels of
      genetic diversity through post-glacial re-colonization. This diversity has
      subsequently been partitioned into population fragments that have recently lost
      diversity at a rate corresponding to the current population-size estimates. We
      conclude that the British population fragments retain sufficient genetic
      resources to be the basis of conservation and re-planting programmes. Use of
      markers with different mutation rates gives us greater confidence and insight
      than one marker set could have alone, and we suggest that RAD-SSRs are
      particularly useful as high mutation-rate marker set with a well-specified
      ascertainment bias, which are widely available yet often neglected in existing
      RAD datasets.

PMID- 30111883
TI  - Decoding topologically associating domains with ultra-low resolution Hi-C data by
      graph structural entropy.
AB  - Submegabase-size topologically associating domains (TAD) have been observed in
      high-throughput chromatin interaction data (Hi-C). However, accurate detection of
      TADs depends on ultra-deep sequencing and sophisticated normalization procedures.
      Here we propose a fast and normalization-free method to decode the domains of
      chromosomes (deDoc) that utilizes structural information theory. By treating Hi-C
      contact matrix as a representation of a graph, deDoc partitions the graph into
      segments with minimal structural entropy. We show that structural entropy can
      also be used to determine the proper bin size of the Hi-C data. By applying deDoc
      to pooled Hi-C data from 10 single cells, we detect megabase-size TAD-like
      domains. This result implies that the modular structure of the genome spatial
      organization may be fundamental to even a small cohort of single cells. Our
      algorithms may facilitate systematic investigations of chromosomal domains on a
      larger scale than hitherto have been possible.

PMID- 30111884
TI  - Resolution of chronic inflammatory disease: universal and tissue-specific
      concepts.
AB  - Inflammation and its resolution is under-studied in medicine despite being
      essential for understanding the development of chronic inflammatory disease. In
      this review article, we discuss the resolution of inflammation in both a
      biological and translational context. We introduce the concept of impaired
      resolution leading to diseases like rheumatoid arthritis, Crohn's disease, and
      asthma, as well as the cellular and molecular components that contribute to
      resolution of joint, gut, and lung inflammation, respectively. Finally, we
      discuss potential intervention strategies for fostering the resolution process,
      and their implications for the therapy of inflammatory diseases.

PMID- 30111885
TI  - The first transmembrane region of complement component-9 acts as a brake on its
      self-assembly.
AB  - Complement component 9 (C9) functions as the pore-forming component of the
      Membrane Attack Complex (MAC). During MAC assembly, multiple copies of C9 are
      sequentially recruited to membrane associated C5b8 to form a pore. Here we
      determined the 2.2 A crystal structure of monomeric murine C9 and the 3.9 A
      resolution cryo EM structure of C9 in a polymeric assembly. Comparison with other
      MAC proteins reveals that the first transmembrane region (TMH1) in monomeric C9
      is uniquely positioned and functions to inhibit its self-assembly in the absence
      of C5b8. We further show that following C9 recruitment to C5b8, a conformational
      change in TMH1 permits unidirectional and sequential binding of additional C9
      monomers to the growing MAC. This mechanism of pore formation contrasts with
      related proteins, such as perforin and the cholesterol dependent cytolysins,
      where it is believed that pre-pore assembly occurs prior to the simultaneous
      release of the transmembrane regions.

PMID- 30111886
TI  - Activation of mineralocorticoid receptor by ecdysone, an adaptogenic and anabolic
      ecdysteroid, promotes glomerular injury and proteinuria involving overactive
      GSK3beta pathway signaling.
AB  - Ecdysone is an arthropod molting hormone and has been marketed as a non
      androgenic natural anabolic and adaptogen. However, the safety profile of
      ecdysone is largely undetermined. After ecdysone treatment for 2 weeks, mice
      developed albuminuria with histologic signs of glomerular injury, including
      hypertrophy, mesangial expansion, mild glomerulosclerosis and podocyte injury. A
      direct glomerulopathic activity of ecdysone seems to contribute, since addition
      of ecdysone to cultured glomerular cells induced cytopathic changes, including
      apoptosis, activation of mesangial cells, podocyte shape changes and a decreased
      expression of podocyte markers. To explore the molecular target responsible for
      the pathogenic actions, we employed an in silico modeling system of compound
      protein interaction and identified mineralocorticoid receptor (MR) as one of the
      top-ranking proteins with putative interactions with ecdysone. The molecular
      structure of ecdysone was highly homologous to mineralocorticoids, like
      aldosterone. Moreover, ecdysone was capable of both inducing and activating MR,
      as evidenced by MR nuclear accumulation in glomerular cells both in vitro and in
      vivo following ecdysone treatment. Mechanistically, glycogen synthase kinase
      (GSK) 3beta, which has been recently implicated in pathogenesis of glomerular
      injury and proteinuria, was hyperactivated in glomeruli in ecdysone-treated mice,
      concomitant with diverse glomerulopathic changes. In contrast, spironolactone, a
      selective blockade of MR, largely abolished the cytopathic effect of ecdysone in
      vitro and attenuated albuminuria and glomerular lesions in ecdysone treated mice,
      associated with a mitigated GSK3beta overactivity in glomeruli. Altogether,
      ecdysone seems able to activate MR and thereby promote glomerular injury and
      proteinuria involving overactive GSK3beta pathway signaling.

PMID- 30111887
TI  - Wound Healing in Streptozotocin-Induced Diabetic Rats Using Atmospheric-Pressure
      Argon Plasma Jet.
AB  - In this study, we used an argon-based round atmospheric-pressure plasma jet
      (APPJ) for enhancing wound healing in streptozotocin (STZ) induced diabetic rats.
      The APPJ was characterized by optical emission spectroscopy. We induced Type 1
      and Type 2 diabetes in rats with different amounts of STZ combined with normal
      and high-fat diets, respectively. The wound area ratio of all the plasma-treated
      normal and diabetic groups was greatly reduced (up to 30%) compared with that of
      the untreated groups during healing. Histological analysis revealed faster re
      epithelialization, collagen deposition, less inflammation, and a complete skin
      structure in the plasma-treated groups was found as compared with the untreated
      control groups. In addition, the new blood vessels of plasma-treated tissues
      decreased more than untreated tissues in the middle (Day 14) and late (Day 21)
      stages of wound healing. The plasma-treated wounds demonstrated more transforming
      growth factor beta (TGF-beta) expression in the early stage (Day 7), whereas they
      decreased in the middle and late stages of wound healing. The levels of
      superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)
      increased after plasma treatment. In addition, plasma-treated water had a higher
      concentration of hydrogen peroxide, nitrite and nitrate when the plasma treatment
      time was longer. In summary, the proposed argon APPJ based on the current study
      could be a potential tool for treating diabetic wounds.

PMID- 30111888
TI  - A Molecularly Modulated Mode-Locked Laser.
AB  - A mode-locked laser operating at a frequency over 10 THz is reported, which is
      three orders of magnitude greater than a standard mode-locked laser. The system
      used molecules with a Raman gain as an amplifier, while coherent molecular
      motions were used for optical modulation. Molecules in a high-finesse optical
      cavity modulated a continuous-wave beam to produce a train of ultrashort optical
      pulses at a repetition rate corresponding to the frequency of molecular motion.
      Phase-locking was achieved by an appropriate compensation of the total dispersion
      of the optical cavity. Thus, the oscillating multiple longitudinal modes were all
      coupled under phase-matching conditions of parametric four-wave mixing.

PMID- 30111890
TI  - Stress affects the epigenetic marks added by natural transposable element
      insertions in Drosophila melanogaster.
AB  - Transposable elements are emerging as an important source of cis-acting
      regulatory sequences and epigenetic marks that could influence gene expression.
      However, few studies have dissected the role of specific transposable element
      insertions on epigenetic gene regulation. Bari-Jheh is a natural transposon that
      mediates resistance to oxidative stress by adding cis-regulatory sequences that
      affect expression of nearby genes. In this work, we integrated publicly available
      ChIP-seq and piRNA data with chromatin immunoprecipitation experiments to get a
      more comprehensive picture of Bari-Jheh molecular effects. We showed that Bari
      Jheh was enriched for H3K9me3 in nonstress conditions, and for H3K9me3, H3K4me3
      and H3K27me3 in oxidative stress conditions, which is consistent with expression
      changes in adjacent genes. We further showed that under oxidative stress
      conditions, H3K4me3 and H3K9me3 spread to the promoter region of Jheh1 gene.
      Finally, another insertion of the Bari1 family was associated with increased
      H3K27me3 in oxidative stress conditions suggesting that Bari1 histone marks are
      copy-specific. We concluded that besides adding cis-regulatory sequences, Bari
      Jheh influences gene expression by affecting the local chromatin state.

PMID- 30111889
TI  - Nomogram for prediction of non-proliferative diabetic retinopathy in juvenile
      onset type 1 diabetes: a cohort study in an Asian population.
AB  - The need for screening for retinopathy in patients with type 1 diabetes mellitus
      (T1DM) has been emphasised, but diagnostic delays were reported when screening
      was done at fixed intervals. To establish an individualised risk-prediction model
      to assist screening non-proliferative diabetic retinopathy (NPDR) in T1DM, we
      performed a retrospective cohort study enrolling participants in the Chang Gung
      Juvenile Diabetes Eye Study. There were 413 patients with 12 381 records analysed
      from 2005 to 2015. A time-dependent Cox proportional hazard analysis was used to
      evaluate the risks of NPDR development and a nomogram with risk-stratification
      indicators was established based on the results. During 97 months of follow-up,
      43 of 413 patients (10.4%) developed NPDR. Male sex (HR: 0.4, 95% CI: 0.19-0.85),
      age 5-14 years at onset of T1DM (6.38, 2.41-16.87), duration of diabetes (1.57,
      1.41-1.75), and hemoglobin A1c level (1.56, 1.35-1.80) were independently
      associated with NPDR. Using the nomogram offers a quick method in the clinical
      setting to interpret the risk of NPDR development. Based on its weighting, each
      of the independent factors is allocated a score, and the total points indicate
      the probabilities of NPDR occurring within 6 months, 1 year, and 3 years.

PMID- 30111892
TI  - Thermal spin fluctuations in CoCrFeMnNi high entropy alloy.
AB  - High entropy alloys based on 3d transition metals display rich and promising
      magnetic characteristics for various high-technology applications. Understanding
      their behavior at finite temperature is, however, limited by the incomplete
      experimental data for single-phase alloys. Here we use first-principles alloy
      theory to investigate the magnetic structure of polymorphic CoCrFeMnNi in the
      paramagnetic state by accounting for the longitudinal spin fluctuations (LSFs) as
      a function of temperature. In both face-centered cubic (fcc) and hexagonal close
      packed (hcp) structures, the LSFs induce sizable magnetic moments for Co, Cr and
      Ni. The impact of LSFs is demonstrated on the phase stability, stacking fault
      energy and the fcc-hcp interfacial energy. The hcp phase is energetically
      preferable to the fcc one at cryogenic temperatures, which results in negative
      stacking fault energy at these conditions. With increasing temperature, the
      stacking fault energy increases, suppressing the formation of stacking faults and
      nano-twins. Our predictions are consistent with recent experimental findings.

PMID- 30111891
TI  - Fluorescence detection of DNA mismatch repair in human cells.
AB  - Mismatched base pairs, produced by nucleotide misincorporation by DNA polymerase,
      are repaired by the mismatch repair (MMR) pathway to maintain genetic integrity.
      We have developed a method for the fluorescence detection of the cellular MMR
      ability. A mismatch, which would generate a stop codon in the mRNA transcript
      unless it was repaired, was introduced into the gene encoding the enhanced green
      fluorescent protein (EGFP) in an expression plasmid. When MMR-proficient HeLa
      cells were transformed with this plasmid, the production of active EGFP was
      observed by fluorescence microscopy. It was assumed that the nick required to
      initiate the MMR pathway was produced non-specifically in the cells. In contrast,
      fluorescence was not detected for three types of MMR-deficient cells, LoVo,
      HCT116, and DLD-1, transformed with the same plasmid. In addition, the expression
      of a red fluorescent protein gene was utilized to avoid false-negative results.
      This simple fluorescence method may improve the detection of repair defects, as a
      biomarker for cancer diagnosis and therapy.

PMID- 30111893
TI  - Publisher Correction: Inactivating hepatic follistatin alleviates hyperglycemia.
AB  - In the version of this article originally published, the y axis labels in Fig.
      4b,d were incorrect. In Fig. 4b, the unit on the label was (ng mg-1). This should
      have been (ng/ml). In Fig. 4d, the y axis label was Serum Fst (ng ml-1). It
      should have been Serum insulin (ng/ml). The errors have been corrected in the
      HTML and PDF versions of this article.

PMID- 30111895
TI  - A New Infrastructure for Monitoring Social Mobility in the United States.
AB  - The country's capacity to monitor trends in social mobility has languished since
      the last major survey on U.S. social mobility was fielded in 1973. It is
      accordingly difficult to evaluate recent concerns that social mobility may be
      declining or to develop mobility policy that is adequately informed by evidence.
      This article presents a new initiative, dubbed the American Opportunity Study
      (AOS), that would allow the country to monitor social mobility efficiently and
      with great accuracy. The AOS entails developing the country's capacity to link
      records across decennial censuses, the American Community Survey, and
      administrative sources. If an AOS of this sort were assembled, it would open up
      new fields of social science inquiry; increase opportunities for evidence-based
      policy on poverty, mobility, child development, and labor markets; and otherwise
      constitute a new social science resource with much reach and impact.

PMID- 30111896
TI  - Intergenerational Mobility in the United States and Great Britain: A Comparative
      Study of Parent-Child Pathways.
AB  - We build on cross-national research to examine the relationships underlying
      estimates of relative intergenerational mobility in the United States and Great
      Britain using harmonized longitudinal data and focusing on men. We examine
      several pathways by which parental status is related to offspring status,
      including education, labor market attachment, occupation, marital status, and
      health, and perform several sensitivity analyses to test the robustness of our
      results. We decompose differences between the two nations into that part
      attributable to the strength of the relationship between parental income and the
      child's characteristics and the labor market return to those child
      characteristics. We find that the relationships underlying these
      intergenerational linkages differ in systematic ways between the two nations. In
      the United States, primarily because of the higher returns to education and
      skills, the pathway through offspring education is relatively more important than
      it is in Great Britain; by contrast, in Great Britain the occupation pathway
      forms the primary channel of intergenerational persistence.

PMID- 30111897
TI  - Comment.

PMID- 30111894
TI  - PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal
      nucleic-acid sensing.
AB  - The sensing of microbial genetic material by leukocytes often elicits beneficial
      pro-inflammatory cytokines, but dysregulated responses can cause severe
      pathogenesis. Genome-wide association studies have linked the gene encoding
      phospholipase D3 (PLD3) to Alzheimer's disease and have linked PLD4 to rheumatoid
      arthritis and systemic sclerosis. PLD3 and PLD4 are endolysosomal proteins whose
      functions are obscure. Here, PLD4-deficient mice were found to have an
      inflammatory disease, marked by elevated levels of interferon-gamma (IFN-gamma)
      and splenomegaly. These phenotypes were traced to altered responsiveness of PLD4
      deficient dendritic cells to ligands of the single-stranded DNA sensor TLR9.
      Macrophages from PLD3-deficient mice also had exaggerated TLR9 responses.
      Although PLD4 and PLD3 were presumed to be phospholipases, we found that they are
      5' exonucleases, probably identical to spleen phosphodiesterase, that break down
      TLR9 ligands. Mice deficient in both PLD3 and PLD4 developed lethal liver
      inflammation in early life, which indicates that both enzymes are needed to
      regulate inflammatory cytokine responses via the degradation of nucleic acids.

PMID- 30111898
TI  - The personalization of engagement: the symbolic construction of social media and
      grassroots mobilization in Canadian newspapers.
AB  - This article explores the symbolic construction of civic engagement mediated by
      social media in Canadian newspapers. The integration of social media in politics
      has created a discursive opening for reimagining engagement, partly as a result
      of enthusiastic accounts of the impact of digital technologies upon democracy. By
      means of a qualitative content analysis of Canadian newspaper articles between
      2005 and 2014, we identify several discursive articulations of engagement: First,
      the articles offer the picture of a wide range of objects of engagement,
      suggesting a civic body actively involved in governance processes. Second,
      engagement appears to take place only reactively, after decisions are made.
      Finally, social media become the new social glue, bringing isolated individuals
      together and thus enabling them to pressure decision-making institutions. We
      argue that, collectively, these stories construct engagement as a deeply personal
      gesture that is nevertheless turned into a communal experience by the affordances
      of technology. The conclusion unpacks what we deem as the ambiguity at the heart
      of this discourse, considering its implications for democratic politics and
      suggesting avenues for the further monitoring of the technologically enabled
      personalization of engagement.

PMID- 30111899
TI  - Public service media, universality and personalisation through algorithms:
      mapping strategies and exploring dilemmas.
AB  - This contribution compares personalisation strategies of public service media
      (PSM) and how these are reconciled with PSM's core values, especially
      universality. To this end, it combines mapping of a sample of PSM with in-depth
      analysis of Flemish VRT and Norwegian NRK. The theoretical framework discusses
      universality in relationship to PSM's historical remit and to contemporary
      personalisation through digital options like algorithms. Subsequently, strategies
      of the sampled PSM are analysed, using data from documents, an online survey and
      interviews. Results suggest that most PSM, including VRT and NRK, engage in
      implicit and explicit digital personalisation, yet vary in type of engagement and
      in views on how personalisation strengthens or threatens universality. It is
      argued that histories and the understanding of technology within specific
      institutions affect their personalisation approach. We argue that policies focus
      on news and information but that negotiating universality and personalisation,
      while dealing with issues like filter bubbles and privacy, extends to the entire
      range of PSM programmes and goals.

PMID- 30111900
TI  - Scandal mining: political nobodies and remediated visibility.
AB  - This article considers the 2015 federal election in Canada as the emergence of
      seemingly citizen-led practices whereby candidates' past missteps are unearthed
      and distributed through social and news media channels. On first pass, these
      resemble citizen-led engagements through digital media for potentially unmappable
      political goals, given the dispersed and either non-partisan or multi-partisan
      nature of these engagements. By bringing together journalistic accounts and
      social media coverage alongside current scholarship on citizenship and
      visibility, this case study traces the possibility of political accountability
      and the political weaponisation of mediated visibility through the targeted
      extraction of candidate details from dispersed profiles, communities and
      databases.

PMID- 30111901
TI  - Fair compensation for victims of human trafficking? A case study of the Dutch
      injured party claim.
AB  - Any person who has been a victim of human trafficking has a right to
      compensation. Compensation entails the reimbursement of material and immaterial
      damages a trafficked person has suffered. In spite of the internationally
      recognized right to compensation, the number of trafficked persons in Europe
      having actually received any reimbursement is very low. The present study
      identifies obstacles to compensation by analysing the Dutch injured party claim.
      It uses 190 case files covering the period 2013-2014. The empirical results show
      several issues. Only an estimated 4% of all registered victims claim compensation
      in the criminal court. A fifth of these claims are inadmissible. Admissible
      claims are on average awarded only half of the claimed amount. A major reason for
      this is how difficult it is to estimate damages accurately. This is, in many
      cases, related to a lack of proof, caused by for example lack of records,
      insufficient financial investigation, and incomplete testimonies, which result in
      only minimum amounts being awarded. Additionally, judges are often inclined to
      dismiss the claim or award a minimum, even in those cases where evidence is
      available. As a result, compensation is often not in line with damages that have
      actually been suffered.

PMID- 30111902
TI  - More than support to court: Rape victims and specialist sexual violence services.
AB  - This article explores the involvement of specialist sexual violence services,
      including Independent Sexual Violence Advisers (ISVAs), in supporting
      victims/survivors of rape and sexual abuse to engage with the criminal justice
      system (CJS) in England and Wales. The underpinning research, conducted in one
      area of England, included referral data from the police and key specialist sexual
      violence services, interviews with 15 victims/survivors of sexual violence in
      contact with the police and specialist services, and interviews with 14
      practitioners from sexual violence and related services. We examine the complex
      needs of victims/survivors of sexual violence (who have experienced historical
      child sexual abuse, acquaintance rape or rape in the context of intimate partner
      abuse), how their needs differ and vary over time, and the ways in which these
      diverse and changing needs are met by specialist sexual violence services. Non
      specialist agencies, such as statutory mental health services, are unable to
      provide similarly targeted responses. The research found that specialist sexual
      violence services play particularly crucial roles through the use of approaches
      that can be characterised as flexible, enabling, holding and mending. However,
      this important work could easily be lost in the current climate of local service
      commissioning, to the great detriment of victims/survivors of sexual violence.

PMID- 30111903
TI  - Image Quality and Segmentation.
AB  - Algorithms for image segmentation (including object recognition and delineation)
      are influenced by the quality of object appearance in the image and overall image
      quality. However, the issue of how to perform segmentation evaluation as a
      function of these quality factors has not been addressed in the literature. In
      this paper, we present a solution to this problem. We devised a set of key
      quality criteria that influence segmentation (global and regional): posture
      deviations, image noise, beam hardening artifacts (streak artifacts), shape
      distortion, presence of pathology, object intensity deviation, and object
      contrast. A trained reader assigned a grade to each object for each criterion in
      each study. We developed algorithms based on logical predicates for determining a
      1 to 10 numeric quality score for each object and each image from reader-assigned
      quality grades. We analyzed these object and image quality scores (OQS and IQS,
      respectively) in our data cohort by gender and age. We performed recognition and
      delineation of all objects using recent adaptations [8, 9] of our Automatic
      Anatomy Recognition (AAR) framework [6] and analyzed the accuracy of recognition
      and delineation of each object. We illustrate our method on 216 head & neck and
      211 thoracic cancer computed tomography (CT) studies.

PMID- 30111904
TI  - Endogenous Selection Bias: The Problem of Conditioning on a Collider Variable.
AB  - Endogenous selection bias is a central problem for causal inference. Recognizing
      the problem, however, can be difficult in practice. This article introduces a
      purely graphical way of characterizing endogenous selection bias and of
      understanding its consequences (Hernan et al. 2004). We use causal graphs (direct
      acyclic graphs, or DAGs) to highlight that endogenous selection bias stems from
      conditioning (e.g., controlling, stratifying, or selecting) on a so-called
      collider variable, i.e., a variable that is itself caused by two other variables,
      one that is (or is associated with) the treatment and another that is (or is
      associated with) the outcome. Endogenous selection bias can result from direct
      conditioning on the outcome variable, a post-outcome variable, a post-treatment
      variable, and even a pre-treatment variable. We highlight the difference between
      endogenous selection bias, common-cause confounding, and overcontrol bias and
      discuss numerous examples from social stratification, cultural sociology, social
      network analysis, political sociology, social demography, and the sociology of
      education.

PMID- 30111905
TI  - Nano-bio interactions.

PMID- 30111907
TI  - Osseodensification - A novel approach in implant dentistry.
AB  - Primary stability in dental implants is an essential factor for achieving
      successful osseointegration. Surgical procedure and bone quality are among the
      most common factors that affect primary stability. It is also crucial to achieve
      high-insertion torque which is important for obtaining primary stability.
      Maintaining sufficient bone bulk and density is essential to achieve necessary
      bone-to-implant contact for obtaining a biomechanically stable implant. A new
      concept for osteotomy called osseodensification (OD) has been at the forefront of
      changes in surgical site preparation in implantology. This relatively new concept
      with universally compatible drills has been proposed to help in better osteotomy
      preparation, bone densification, and indirect sinus lift and also achieve bone
      expansion at different sites of varying bone densities. This procedure has also
      shown improvement in achieving better implant primary stability and better
      osteotomy than conventional implant drills. A systematic review was undertaken to
      analyze if OD procedure had any advantages over conventional osteotomy on bone
      density and primary stability. An electronic database search was conducted in
      PubMed using keywords such as "OD," "implant primary stability," "implant bone
      density," and "implant osteotomy." A total of 195 articles were collected and
      subjected to screening using inclusion and exclusion criteria. A literature
      review was done, following which it was seen that the use of versah drills for
      bone OD resulted in undersized osteotomy compared to conventional drills. It also
      resulted in improved bone density and increase in percentage bone volume and bone
      to-implant contact, thereby improving implant stability.

PMID- 30111906
TI  - Systematic analysis of factors that cause loss of preload in dental implants.
AB  - : Screw loosening is the most common factor associated with dental implant
      failure. One of the major cause for screw loosening is the "loss of preload".
      Several factors including screw geometry, material properties particularly
      stiffness, surface texture and condition of mating surfaces, degree of
      lubrication, rate of tightening, integrity of joint etc. Objective: This review
      analyses the factors that are responsible for the loss of preload. Material and
      Methods: Screw geometry, Implant- Abutment Connection type (external hexagon
      platform, morse taper), Material properties viz Stiffness, Resilience, Materials
      viz gold, titanium, titanium alloy, Surface texture of the abutment screw,
      Condition of mating surfaces, Lubrication, Torque value, Rate of tightening (10,
      20, 35N and retorque after 10mins) are taken into consideration in this study.
      The MEDLINE-PubMed database was searched from September 2016 to 10 years
      previously. Several journals were hand searched and from cross references. The
      outcome analysed are the factors that are responsible for loss of preload.
      Results: The search yielded 84 articles. After excluding duplicated abstracts and
      applying the inclusion and exclusion criteria, 36 studies were eligible for
      analysis. The result shows that loss of preload can occurs depending upon the
      type of material used, torque method, torque sequences, abutment connection type,
      influence of lubrication, abutment collar length. However we detected some
      potential limitations in the studies selected, mainly a minimum number of samples
      used for the study. Hence we suggest further studies to guarantee an excellence
      in methodological quality. Conclusion: Based on the available data it can be
      summarized that the knowledge of preload loss must be known for the clinicians to
      avoid such screw loosening and subsequent implant failure.

PMID- 30111909
TI  - Comparison between shear forces applied on the overlay-dental tissue interface
      using different bonding techniques: An in vitro study.
AB  - Aim: The aim of this study was to compare the adhesion of glass-ceramic overlays
      to tooth structure, under the effect of shear forces, using different bonding
      systems. Materials and Methods: Thirty healthy lower third molars were selected
      and randomly allocated into three groups (n = 10). Group 1: overlays bonded to
      tooth structure using Panavia V5 with immediate dentin sealing (IDS); Group 2:
      overlays bonded using Panavia V5 without IDS; and Group 3: overlays bonded using
      heated composite combined with a bonding agent with IDS. All the restorations
      were made of glass-ceramic (Suprinity, Vita). The restored teeth were then stored
      in distilled water for 7 days and at room temperature. Shear forces were applied
      using a universal testing machine. Load and displacement were recorded at
      intervals of 0.1 s. A statistical analysis was used to compare the groups.
      Results: The mean resistance to fractures +/- standard deviation obtained for the
      Groups 1, 2, and 3 was, respectively, 15.7440 +/- 2.13, 12.0750 +/- 1.41, and
      8.33364 +/- 2.85 MPa. The analysis of variance was highly significant (P < 0.001)
      allowing us to reject the null hypothesis of equality between the three groups.
      Comparisons between pairs also provided significant results. Conclusion: Bonding
      using Panavia V5 with IDS showed a better resistance to shear forces when
      compared to other bonding techniques. The application of IDS increased the
      adhesion.

PMID- 30111908
TI  - Retention failures in cement- and screw-retained fixed restorations on dental
      implants in partially edentulous arches: A systematic review with meta-analysis.
AB  - Purpose: This systematic review aimed to evaluate retention failures in cement-
      and screw-retained fixed restorations on dental implants in partially edentulous
      arches. Methods: The relevant articles were retrieved from MEDLINE (PubMed),
      Cochrane Library, and EBSCO electronic databases for articles published from
      January 1995 to January 2016 and were restricted to randomized controlled trials
      and retrospective and prospective studies on human subjects that were reported in
      English. A further hand search was conducted on individual journals and reference
      list of the articles found. Reviewed studies which reported retention failures in
      fixed implant-supported prostheses using screw and cement retention mechanism.
      Information on the type and nature of restoration, as well as different luting
      cement, were also collected. Results: Thirty-three articles were finalized, 20
      short-term clinical studies (up to 5 years) and 13 long-term studies (>=5 years).
      Out of 33 studies, 16 studies were included in meta-analysis, 8 in short-term and
      8 in long-term studies. The results of the meta-analysis for short-term studies
      showed statistically significant difference between cement-retained and screw
      retained prosthesis, with the forest plot favoring cement-retained prostheses
      (risk ratio [RR]: 0.26; confidence interval [CI]: 0.09-0.74; P < 0.0001; I2 =
      79%). In long-term studies, the forest plot revealed statistically significant
      difference between both retention systems favoring cement-retained prostheses
      (RR: 0.31; CI: 0.13-0.76; P = 0.03; I2 = 56%). Conclusion: Analysis of the short-
      and long-term studies shows lesser retention failures with cement-retained
      prostheses when compared to screw-retained prostheses. Further, multicentric,
      high-quality randomized controlled studies with long-term observations and
      modified cementation protocols can yield higher grades of recommendation to avoid
      retention failures.

PMID- 30111910
TI  - Structurofunctional analysis based on postinsertion problems with complete
      dentures in Moradabad, North India: A cross-sectional study.
AB  - Background: Complaints with complete dentures is a common and expected
      phenomenon. However the type and character of complaint varies between population
      and is influenced by the socio economic condition, prevalent dental awareness
      etc. This study attempts to find the most common complaints with complete
      dentures, their causes and also presents a classification of the same. Method: A
      cross-sectional analytical study was conducted by performing a survey on a sample
      of population over an 18 month period utilizing a customized questionnaire. The
      complaints were divided into four categories viz. discomfort, retention,
      esthetics and miscellaneous. Consequently each denture was evaluated for
      structural and functional defects. The findings were classified into error in
      denture base, physiopsychological, error in occlusion and teeth selection. The
      data was statistically analyzed. Results: Error in denture base was the
      predominant cause of complaints. However physiopsychological and error in
      occlusion and teeth selection were also important second factors in certain
      groups of complaints. Highest number of complaints (23.07%) belongs to discomfort
      in mandibular posterior region. While the least number of complaints are
      concerned with speech as reported by both males and females (both at 2.02%).
      Conclusion: Discomfort with complete dentures was the largest complaint reported
      followed by loss of retention with esthetics and miscellaneous complaints.
      Discomfort in mandibular posterior region was the most frequent complaint
      reported while speech related complaints were least in number. Most common cause
      of complaints was error in denture base.

PMID- 30111912
TI  - A cross-sectional study to explore the reasons to visit a quack for prosthodontic
      solutions.
AB  - Purpose: Since the services of a qualified practitioner are not easily accessible
      to the vast majority of the population, the gap is filled literally at the
      roadside by the ubiquitous unqualified practitioner. The present article
      emphasizes on the outcome of prosthesis which the quacks deliver for the
      replacement of natural teeth. Materials and Methods: In the present study, we had
      explored the reason why people visit these quacks, the complications which they
      face after using fixed dentures delivered by the quack and some solutions to
      tackle quackery. Data were recorded as a closed-ended questionnaire for 132
      participants. Results: Nearly 64% of subjects were facing a problem with the
      denture and 74.2% of the participants were not even aware of any qualified
      practitioner. Most common reason to visit the quack was lack of awareness; other
      reasons were economy, proximity to house, comfortable fixed option, single
      appointment, and referrals. Conclusion: Awareness and orientation programs are
      possible solutions to spread knowledge, change attitudes, and practice. In
      addition to that, there should be strict laws abolishing the practice of
      unqualified practitioner.

PMID- 30111911
TI  - Comparative study to evaluate bone loss during osteotomy using standard drill,
      bone trephine, and alveolar expanders for implant placement.
AB  - Statement of Problem: Various osteotomy modalities seem to have an impact on the
      primary and secondary stability of the dental implant. The available literature
      lacks the comparison of various available osteotomy modalities used for the
      dental implant placement and its effects on the initial surgical bone removal.
      Purpose: The purpose of this study is to compare and evaluate the osteotomy sites
      created using standard drill, bone trephine, and alveolar expanders for dental
      implant surgery. Materials and Methods: The study was done on ten goat
      hemimandibles. Three osteotomy sites were prepared at the inferior border of the
      mandible using standard drill, trephine, and alveolar expander in each
      hemimandibles and the sites were subjected to cone-beam computed tomography
      (CBCT). The CBCT images obtained were compared for the amount of cortical bone
      and bone marrow loss at osteotomy sites in different techniques. Results: The
      mean and standard deviation of loss of cortical bone with standard drills,
      trephines, and alveolar expanders was 3.62 +/- 4.216 * 10-2, 3.6 +/- 4.681 * 10
      16 and 3.15 +/- 7.071 * 10-2. At the middle-third region, the loss of marrow bone
      was 3.38 +/- 7.88 * 10-2, 2.15 +/- 8.498 * 10-2 and 0.03 +/- 9.487 * 10-2, and at
      lower third region, it was 2.3 +/- 4.714 * 10-2, 0.02 +/- 6.325 * 10-2, and 0.0,
      respectively. Conclusion: CBCT images showed minimum bone loss with the use of
      alveolar expander which may be due to the lateral bone condensation rather the
      removal of the marrow. Trephine showed less marrow removal in comparison to the
      standard drill used for dental implant surgery.

PMID- 30111913
TI  - Evaluation of positional accuracy in multiple implants using four different
      splinting materials: An in vitro study.
AB  - Background: Prosthesis misfit plays an important role in complications such as
      occlusal and abutment screw loosening and fracture in implant restorations.
      Reproducing the intraoral relationship of implants through impression procedures
      is the first step in achieving an accurate, passively fitting prosthesis to
      ensure maximum accuracy. Hence, splinting of multiple implants with most accurate
      material may be a valid option. Context: The results of splinting multiple
      implants are always inconsistent, and there is limited literature available to
      compare the accuracy of impression techniques as well as materials. In such
      situation, more and more studies have to be done to prove the efficacy and
      accuracy of each splinting materials. Aim: The aim of the study was to evaluate
      the positional accuracy in multiple implants using acrylic resin, pattern resin,
      flowable composite, and bite registration paste. Subjects and Methods: An acrylic
      resin model was fabricated into which four implant analogs placed. The copings
      attached were splinted with dental floss onto which acrylic resin was added,
      which was sectioned and rewelded (Group A). Similarly, pattern resin, flowable
      composite, and bite registration material were added which were considered as
      Group B, C, and D, respectively. Impressions were made in vinyl polysiloxane and
      analogs were attached. The casts retrieved from each group were analysed for the
      positional accuracy of implants. Statistical Analysis: One-way ANOVA was done to
      analyze the significant difference between the four implant analogs of each group
      with the master model. The confidence interval was also calculated to assess the
      accuracy. Results: It was observed that all materials are equally effective for
      the accurate reproduction of implant positions. There was no significant
      difference between the centroids of implant analogues of master model and the
      mean of interimplant distance 1 and 2, 1 and 4, 3 and 4 and 2 and 4 in each
      group. The P-values were >0.05. The accuracy of splinting materials were analysed
      and it showed that splinting with flowable composite (Group C) as well as bite
      registration paste were in par with the conventionally used materials like
      pattern resin and acrylic resin. Conclusions: Results showed that flowable
      composite as well as bite registration material can be recommended as splinting
      material of choice for multiple implant cases, as these exhibited similar results
      like other groups (pattern resin and acrylic resin) which are conventionally
      used.

PMID- 30111914
TI  - Wettability of three denture base materials to human saliva, saliva substitute,
      and distilled water: A comparative in vitro study.
AB  - Aim: The purpose of this study was to compare the wettability of saliva, a saliva
      substitute, and distilled water to three denture base materials. Materials and
      Methods: Thirty specimens of each denture base material: Heat cure
      polymethylmethacrylate (DPI heat cure), high-impact polymethylmethacrylate
      (Trevalon HI), and nylon (Valplast) were fabricated. The specimens of each
      denture base material were divided into three groups of ten specimens. The
      advancing and receding contact angles of three media: a commercially available
      carboxymethylcellulose-based saliva substitute (WET MOUTH), human whole saliva,
      and distilled water, with each denture base material were determined using a
      goniometer. The contact angle hysteresis was calculated as the difference between
      the advancing and receding contact angles. The data were statistically analyzed
      using univariate analysis of variance and Duncan post hoc test. Results: Low
      advancing and receding contact angles were demonstrated on high-impact heat
      polymerized polymethylmethacrylate denture base material. Highest hysteresis
      values were calculated for nylon denture base material. Conclusion: Best
      wettability was demonstrated on high-impact heat-polymerized
      polymethylmethacrylate denture base material. Based on the high hysteresis values
      calculated with nylon denture base material, it would possibly provide better
      denture retention.

PMID- 30111915
TI  - Flexural strength of hydrogen plasma-treated polypropylene fiber-reinforced
      polymethyl methacrylate denture base material.
AB  - Objectives: The present study aimed to evaluate flexural strength of hydrogen
      plasma-treated polypropylene fibers-reinforced polymethyl methacrylate (PMMA)
      polymer composite. Materials and Methods: One control group with no fiber
      reinforcement and 9 polymer composite test groups with varying fiber weight
      percentage (2.5, 5, and 10 Wt%) and aspect ratio (3/220, 6/220, and 12 mm/220
      MUm) were prepared. Flexural strength was measured using Instron. Results: All
      hydrogen plasma-treated polypropylene fiber-reinforced test groups obtained
      significantly higher flexural strength characteristics. Among the test groups, 6
      mm long fibers reinforced in 10 Wt% showed superior flexural strength.
      Conclusion: Hydrogen plasma treatment on polypropylene fiber has a significant
      role in enhancing the adhesion between PMMA polymer matrix and the polypropylene
      fibers and thereby the flexural strength.

PMID- 30111916
TI  - A study on the accuracy of horizontal condylar guidance values in edentulous
      patients using preprosthetic diagnostic radiographs.
AB  - Context: Determination of horizontal condylar guidance (HCG) by various clinical
      and radiographic methods was performed by several investigators. If a correlation
      between HCG values using lateral radiographic tracing and protrusive
      interocclusal records can be established, the necessity of performing elaborate
      recording procedures can be eliminated. Aims: The aim of this study is to
      evaluate and to compare the correlation between HCG values in edentulous people
      using the protrusive interocclusal records mounted on a semi-adjustable
      articulator with the manual tracing of panoramic radiograph and lateral
      cephalogram. Materials and Methods: A total of 20 completely edentulous
      individuals of either sex from 45 to 75 years (mean age 63.15 years) fulfilling
      the inclusion criteria were included in this in vivo study. In all the
      participants, HCG angles were determined clinically using protrusive
      interocclusal records and semi-adjustable articulator after intraoral gothic arch
      tracing. Radiographically, it was obtained by cephalometric tracing of panoramic
      radiograph and lateral cephalogram. Results: The present study shows mean HCG +/-
      standard deviation (SD) of 28.17 degrees  +/- 5.99 degrees  for interocclusal
      protrusive record while cephalometric tracing method yielded HCG +/- SD of 38.95
      degrees  +/- 4.77 degrees  and 35.2 degrees  +/- 4.94 degrees  for lateral
      cephalogram and orthopantomogram, respectively. A statistically significant
      positive correlation (P < 0.0001) was found among these three methods.
      Conclusion: HCG can be successfully determined in edentulous participants by
      using three aforementioned methods. HCG values from cephalometric tracing of
      diagnostic radiographs can be used as an adjunct to the clinical method but
      cannot be used independently for programming a semi-adjustable articulator.

PMID- 30111917
TI  - Need for a reliable alternative to custom-made Implant Impression trays: An in
      vitro study comparing accuracy of custom trays versus specialized aluminum stock
      tray.
AB  - Purpose: The aim of the present study was to evaluate and to compare the accuracy
      of implant casts obtained by open tray pick-up impression technique using 2 types
      of custom-made trays and a specialized aluminum stock impression tray. Materials
      and Methods: A heat-cure acrylic resin master model was fabricated. Two implants
      were placed parallel to each other. Ten impressions were made from each group.
      Polyvinylsiloxane impression material with single step putty wash technique was
      used for making all the impressions. The resultant casts obtained were compared
      to the master models with respect to the distances measured between the reference
      points using a stereomicroscope. The data obtained was statistically analyzed
      using one-way ANOVA, Tukey's post hoc procedures, and t-test. Results: Mean value
      obtained was 2.012967 cm (+/-0.007060) for corimplant stock tray, 2.012627 cm (+/
      0.007945) for autopolymerizing acrylic resin tray, 2.010279 cm (+/-0.006832) for
      light-cure hybrid composite tray. P value was calculated to be >0.05; hence,
      there was nonsignificant deviation of observations from standard value in each
      group. Conclusion: Statistically insignificant difference was found between the
      accuracy of casts obtained by the different impression trays. However, light-cure
      hybrid composite trays showed best results followed by autopolymerizing acrylic
      resin trays and Corimplant stock tray.

PMID- 30111918
TI  - Effect of probiotics on the amount and pH of saliva in edentulous patients: A
      Prospective study.
AB  - Context: Probiotics have been prescribed to old aged patients' invariably with or
      without complete dentures for improving their digestive process. It is mentioned
      that probiotics do have an effect in increasing the amount of saliva in the oral
      cavity. Therefore, this study was planned to evaluate the amount and pH of saliva
      after using probiotics for 60 days in completely edentulous patients. Aim: This
      study aims to evaluate the amount and pH of saliva of edentulous patients before
      and after using probiotics. Settings and Design: The interventional prospective
      study was conducted at the department of prosthodontics of the institute.
      Methods: The study was conducted on edentulous patients. The whole unstimulated
      and stimulated saliva was collected at baseline and amount, and pH was measured.
      Then, each patient was given probiotic capsules reaching 3.3 * 107 CFU/g to
      consume daily once for 60 days. Saliva was recollected from patients, and its
      amount and pH was calculated and compared with baseline. Statistical Analysis
      Used: STATAIC-13. Results: On comparison of saliva before and after consuming
      probiotics, there was an increase in the mean unstimulated and stimulated saliva
      from baseline to that after 60 days, the difference being 0.406 and 0.433,
      respectively. The difference was statistically significant with P < 0.001. The
      mean pH at baseline was 7.818 +/- 0.231 which increased after 60 days to 7.825 +/
      0.189, the difference being 0.007. Conclusion: This study concluded that
      probiotics increase the amount of saliva of completely edentulous patients and so
      it can be helpful in patients suffering from xerostomia/hyposalivation.

PMID- 30111920
TI  - Deadly Nipah Outbreak in Kerala: Lessons Learned for the Future.

PMID- 30111919
TI  - Rehabilitation of a maxillectomy patient using intraoral scanning impression
      technology and a computer-aided design/computer-aided manufacturing fabricated
      obturator prosthesis: A clinical report.
AB  - Rehabilitation of a partially dentate postmaxillectomy patient using a novel
      approach is presented in this report. The patient was referred to our practice by
      the oral and maxillofacial surgery department of the local general hospital for
      the evaluation and prosthetic treatment planning. He had undergone biopsy for a
      lesion located in the right quadrant of his maxilla and was scheduled for a
      hemimaxillectomy for removal of a squamous cell carcinoma. A surgical obturator
      was prepared for placement at the time of ablative surgery. Following completion
      of adjuvant radiotherapy and chemotherapy, a digital intraoral impression of the
      remaining maxilla and mandible was obtained, and a computer-aided design/computer
      aided manufacturing obturator removable partial denture utilizing a selective
      laser melting -produced metal framework was fabricated and delivered to the
      patient to restore function and esthetics. The need for conventional impression
      was eliminated leading to a reduction of necessary appointments and more comfort
      to the patient.

PMID- 30111921
TI  - The Association between Arterial Oxygen Tension, Hemoglobin Concentration, and
      Mortality in Mechanically Ventilated Critically Ill Patients.
AB  - Background: Hypoxemia and anemia are common findings in critically ill patients
      admitted to Intensive Care Units. Both are independently associated with
      significant morbidity and mortality. However, the interaction between oxygenation
      and anemia and their impact on mortality in critically ill patients has not been
      clearly defined. We undertook this study to determine whether hemoglobin (Hb)
      level would modify the association between hypoxemia and mortality in
      mechanically ventilated critically ill patients. Methods: We performed a
      retrospective cohort study of all mechanically ventilated adult patients (aged
      >16 years) in the Australian and New Zealand Intensive Care Society Adult Patient
      Database (APD) admitted over a 10-year period. Multivariate hierarchical logistic
      regression was used to assess the relationship between hypoxemia and hospital
      mortality stratified by Hb. Results: Of 1,196,089 patients in the APD, 219,723
      satisfied our inclusion and exclusion criteria. There was a linear negative
      relationship between hypoxemia and hospital mortality which was significantly
      modified when stratified by Hb. Hb independently increased the risk of mortality
      in patients with arterial oxygen tension <102. Conclusions: Hb is an effect
      modifier on the association between oxygenation and mortality.

PMID- 30111922
TI  - Comparison of Mechanical Insufflation-Exsufflation and Endotracheal Suctioning in
      Mechanically Ventilated Patients: Effects on Respiratory Mechanics, Hemodynamics,
      and Volume of Secretions.
AB  - Context: Cough assist (CA) is a device to improve bronchial hygiene of patients
      with secretion in the airways and ineffective cough. Aims: To compare the
      physiological effects and the volume of secretion of mechanical insufflation
      exsufflation (CA device) with isolated endotracheal suctioning in mechanically
      ventilated patients. Settings and Design: Randomized crossover trial. Materials
      and Methods: The patients were randomly allocated to the first technique, then
      the following technique was performed in the next day. We collected the variables
      related to oxygen saturation, hemodynamics (heart rate, systolic blood pressure,
      diastolic blood pressure, and mean arterial pressure [MAP]), and respiratory
      mechanics (tidal volume, minute volume, respiratory rate, and lung compliance and
      resistance), pre- and postimplementation (immediately and after 15 and 30 min),
      and the aspirated volume of secretion. Statistical Analysis Used: We used two-way
      analysis of variance followed by the Student-Newman-Keuls t-test to compare the
      variables at different time points. Student's t-test was used to compare
      secretion volumes. All data were stored and analyzed in SPSS for Windows Version
      19.0. The significance level was set at 5%. Results: Forty-three patients were
      included in the study. When we compared the results before and after the
      application of the techniques, we observed no significant difference in lung
      compliance, pulmonary resistance, MAP, peripheral oxygen saturation, and
      secretion volume in both groups. Conclusions: The mechanical insufflation
      exsufflation does not alter respiratory mechanics and hemodynamic stability, and
      it does not improve airway clearance in mechanically ventilated patients.

PMID- 30111923
TI  - A Questionnaire-based Survey of Physician Perceptions of the Prevalence of
      Antimicrobial Resistance and Their Antibiotic Prescribing Patterns.
AB  - Background: Antibiotic resistance is a serious problem being faced by physicians
      worldwide. This article was designed to study physician perceptions of antibiotic
      resistance and their prescribing patterns. Materials and Methods: A structured
      questionnaire was developed for reporting the prevalence of antibiotic resistance
      as perceived by physicians and recording their antibiotic preferences in specific
      contexts. A total of 539 intensivists across India participated in the study.
      Results: The prevalence of multidrug-resistant (MDR) Gram-negative pathogens was
      reported to be on the rise in Intensive Care Units. The prevalence rate of
      carbapenem-resistant Enterobacteriaceae was reported to be between 20% and 40% by
      33% of the participants. Piperacillin-tazobactam was the preferred beta
      lactam/beta-lactamase inhibitor antibiotic by the majority of intensivists (47%)
      in the treatment of infections caused by extended-spectrum beta-lactamase
      producers. Meropenem was recommended to be used at a higher dose (2 g t.i.d.) by
      41% of intensivists for Pseudomonas/Acinetobacter infections with high minimum
      inhibitory concentration values for meropenem. De-escalation data revealed that
      43% of intensivists "always" would like to de-escalate from carbapenems, based on
      the antibiotic susceptibility data. Minocycline was recommended by 33% for the
      treatment of ventilator-associated pneumonia (VAP) and by 21% for bloodstream
      infections caused by MDR Acinetobacter. Up to 83% of intensivists preferred the
      use of nebulized colistin for the management of VAP/hospital-acquired pneumonia.
      Conclusion: This study reveals that the prevalence of MDR Gram-negative pathogens
      is perceived to be on the rise. Prescription patterns indicate high levels of
      variability. Hence, antibiotic stewardship is essential to standardize antibiotic
      prescriptions not only for efficacy but also to reduce the burden of multiple
      drug resistance.

PMID- 30111924
TI  - Impact of Additional Short Session of Video Training on Performance of Basic Life
      Support Skills in 2nd-Year Medical Students.
AB  - Context: Basic life support (BLS) is a core life-saving skill which everyone
      should know, but knowledge of BLS is poor even among medical students. Aims: The
      aim of our study was to assess the knowledge regarding BLS among medical students
      and see impact of training and also to know whether a short session of video
      training made an impact on their cardiopulmonary resuscitation (CPR) skills.
      Settings and Design: Ninety-two 2nd-year medical students were included in the
      study. Materials and Methods: Their baseline knowledge regarding BLS was assessed
      before workshop with pretest 1. Following workshop posttest 1 and 1 month later,
      posttest 2 was conducted. A short duration video training on BLS was done after
      posttest 2 and its impact was assessed 2 months later with performance of CPR
      skills on a mannequin. Statistical Analysis Used: Data analysis was done using
      SPSS version 23.0. Pearson's Chi-square test was used to evaluate the differences
      between groups for categorized variables. Unpaired and paired t-test was used to
      calculate the difference of means for quantitative variables. Results: There was
      significant improvement in knowledge regarding BLS after the workshop. Even after
      1 month, though there was decline in knowledge, still it was significantly higher
      than the baseline. Short duration video training session did not lead to any
      improvement in BLS skills. Conclusions: BLS training should start early in
      medical curriculum with reinforcement at regular intervals. Single short duration
      video training session did not have any impact on improvement of skills.

PMID- 30111925
TI  - Resurgence of Global Opportunistic Multidrug-resistant Stenotrophomonas
      maltophilia.
AB  - Context: Stenotrophomonas maltophilia is a known nosocomial pathogen which is
      intrinsically resistant to multiple antibiotics. In India, S. maltophilia
      infection has only few case reports. Aim: To determine the incidence of S.
      maltophilia infection from clinical isolates based on the specimen type,
      antibiotic susceptibility pattern, and impact on outcome. Settings and Design:
      One-year retrospective study was done at a tertiary liver care center. Methods:
      Patients with S. maltophilia isolation in clinical samples were selected. Serial
      levels of serum procalcitonin and total leukocyte count were recorded.
      Environmental surveillance was done from the wards of S. maltophilia isolation as
      part of routine practice. Statistical Analysis: Continuous data were compared
      using Kruskal-Wallis test/Mann-Whitney test. The categorical data were compared
      by Chi-square/Fisher's exact test, wherever necessary. Besides this, an
      appropriate analysis like survival was carried out at the time of data analysis.
      Results: One hundred isolates were obtained from eighty patients of six wards.
      The greatest number (44/100, 44%) were from the Liver Coma Intensive Care Unit
      and the lowest (3/100) from the day care. Isolation from the respiratory samples
      was 1.32% and bloodstream infection 0.6%. Of 100 isolates, 12 (12%) were
      resistant to both trimethoprim-sulfamethoxazole and levofloxacin. Conclusion: S.
      maltophilia was effectively isolated from the hospital environment, with two of
      hand impression and three of water samples' positive. Patients with respiratory
      infection had most S. maltophilia isolates. Antibiotic susceptibility revealed
      more resistance than reported in this region.

PMID- 30111926
TI  - Neurological Prognostications for the Therapeutic Hypothermia among Comatose
      Survivors of Cardiac Arrest.
AB  - Background: Currently, there are limited data of prognostic clues for
      neurological recovery in comatose survivors undergoing therapeutic hypothermia
      (TH). We aimed to evaluate clinical signs and findings that could predict
      neurological outcomes, and determine the optimal time for the prognostication.
      Materials and Methods: We retrospectively reviewed database of postarrest
      survivors treated with TH in our hospital from 2006 to 2014. Cerebral performance
      category (CPC), neurological signs and findings in electroencephalography (EEG)
      and brain computed tomography (CT) were evaluated. In addition, the optimal time
      to evaluate neurological status was analyzed. Results: TH was performed in 51
      postarrest patients. Approximately 53% of TH patients survived at discharge and
      33% of the hospital survivors had favorable outcome (CPC1-2). The prognostic
      clues for unfavorable outcome (CPC3-5) at discharge were lack of pupillary light
      response (PLR) and/or gag reflex after rewarming, and the absence of at least one
      of the brainstem reflexes, no eye-opening, or abnormal motor response on the 7th
      day. Myoclonus and seizure could not be used to indicate poor prognosis. In
      addition, prognostic values of EEG and CT findings were inconclusive.
      Conclusions: Our study showed the simple neurological signs helped predict short
      term neurological prognosis. The most reliable sign determining unfavorable
      outcome was the lack of PLR. The optimal time to assess prognosis was either at
      48-72 h or 7 days after return of spontaneous circulation.

PMID- 30111927
TI  - Acute Leukoencephalopathy with Restricted Diffusion.
AB  - Treatment and outcome of children with acute encephalopathy depend on the cause,
      prompt treatment of the underlying cause, and use of adequate supportive
      measures. Many novel causes of acute encephalopathy are emerging where lumbar
      puncture, computed tomography of the head, and routine biochemical testing can be
      normal such as acute disseminated encephalomyelitis and febrile infection-related
      refractory epilepsy syndrome. Magnetic resonance imaging (MRI) plays an important
      role in the workup of children with acute leukoencephalopathy. Despite this in
      few cases, a correct diagnosis is not possible and novel conditions have been
      described in the last decade. One such condition is acute encephalopathy with
      biphasic seizures and restricted diffusion also called as acute
      leukoencephalopathy with restricted diffusion. Here, the routine MRI sequences
      such as T1, T2, and fluid-attenuated inversion recovery sequences can be normal.
      Here, we have reviewed the etiology, types, clinicoradiological features, and
      treatment of this condition.

PMID- 30111928
TI  - Feasibility and Accuracy of a Nonmedical Research Person in Assimilation and
      Calculation of Acute Physiologic Assessment and Chronic Health Evaluation Scores
      in an Indian Intensive Care Unit.
AB  - Background: The Physiologic Assessment and Chronic Health Evaluation (APACHE)
      score assimilation and calculation, as well as other demographic data collection,
      is inherent to research and nonresearch related needs of intensive care. There
      may be a role for well-trained nonmedical personnel to collect this vital
      material to enhance research and the standard of care in the Intensive Care Units
      (ICUs) in countries that are poorly funded and resourced in terms of medical
      personnel. Aims: The aim of this study is to verify the interrater reliability of
      a trained nonmedical personnel and ICU trainee in the collection and calculation
      APACHE scores. Materials and Methods: In a prospective study, two raters who were
      blinded, one a trained nonmedical ward clerk and another an ICU trainee,
      assimilated data and calculated APACHE scores for 60 consecutive patients
      admitted to two tertiary mixed ICUs (with a total of 19 beds). Primary outcomes
      were to assess interrater and interclass correlation as well as the agreement of
      scores between the two raters. Results: There was an excellent correlation of
      APACHE scores (Kappa coefficient of 0.92) and Bland-Altman plot depicted overall
      good agreement with low bias between raters. Conclusions: A well-trained and
      supervised nonmedical research person can assimilate and calculate APACHE II
      scores with good agreement with an ICU trainee. This may help in deriving data
      from medically understaffed ICUs in India, thus promoting much-needed research
      from such ICUs.

PMID- 30111929
TI  - CD14+ Monocytic Cytokines: Impact on Outcome in Severely Injured Patients.
AB  - Introduction: Trauma is one of the leading causes of mortality worldwide. Trauma
      patients, who presented to the hospital casualty department within 24 h of
      injury, further admitted to the Surgical Intensive Care Unit were enrolled in
      this study. Materials and Methods: The aim was to study the peripheral blood
      monocyte activity to produce tumor necrosis factor (TNF-alpha), interleukin-1 (IL
      1) beta, IL-6, and IL-8 in severely injured patients after trauma. Result: A
      total of 28 polytrauma patients were enrolled and observed that the levels of TNF
      alpha, IL-1 beta, IL-6, and IL-8 were significantly decreased and levels of IL-8
      were increased in the fatal patients compared to the healthy controls.
      Conclusion: After trauma, an immediate hyperactivation of circulating monocytes
      is rapidly followed by a substantial paralysis of cell function. Decreased
      activity of monocytes can be used to identify potential fatal immunological
      disruption. Since immunological disruption occurs before clinical symptoms; our
      study proposes an immunological prognostication score for trauma victims.

PMID- 30111930
TI  - In vitro Activity of Fosfomycin against Multidrug-Resistant Urinary and
      Nonurinary Gram-Negative Isolates.
AB  - Background: The era of multidrug-resistant (MDR) Gram-negative bacilli (GNB) has
      renewed interest in fosfomycin. Aim: The present study evaluated the in vitro
      activity of fosfomycin against MDR urinary and nonurinary GNB isolates. Materials
      and Methods: Fosfomycin susceptibility was carried out by agar dilution for a
      total of 279 (142 from urine and 137 from other samples) MDR-GNB. Disk diffusion
      was done for urinary isolates only. Results: Urinary tract isolates had a high
      degree of susceptibility to fosfomycin (overall susceptibility, 90.8%), whereas
      only 42.9% of nonurinary isolates retained susceptibility to the drug. Percentage
      susceptibility rates for urinary and nonurinary isolates of Escherichia coli,
      Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter spp. were 99%,
      91.3%, 66%, 0% and 62%, 44.4%, 32%, 11%, respectively. Conclusion: Fosfomycin
      showed excellent in vitro activity for uropathogens. Large-scale evaluation of
      fosfomycin against MDR systemic isolates is required to evaluate its therapeutic
      efficacy.

PMID- 30111932
TI  - Brain Dead Presentation of Snake Bite.
AB  - Snakebite is considered as a significant public health problem contributing
      considerably to morbidity and mortality. A neurotoxic snake bite can present from
      mild ptosis to complete paralysis with external and internal ophthalmoplegia.
      Three patients presented in emergency intubated outside with deeply comatose,
      fixed dilated pupil, and absent doll's eye reflex mimicking as brain dead.

PMID- 30111931
TI  - The Era of Device Colonizers: Chryseobacterium indologenes Infections from a
      Tertiary Care Center in North India.
AB  - Background: Chryseobacterium indologenes is a hospital environment contaminant
      and can cause healthcare-associated infections. Methods: Patients with C.
      indologenes infections in a tertiary care center in North India for 6 months were
      evaluated for susceptibility patterns, comorbidities, mechanical devices, risk
      factors, and treatment outcomes. The organism was provisionally identified
      phenotypically, and identification was confirmed by the BD Phoenix automated
      microbiology system. Minimum inhibitory concentration values of antibiotic
      susceptibility were determined. Results: A total of 12 isolates of C. indologenes
      were recovered from 11 patients. Five patients had C. indologenes bloodstream
      infection (BSI), one had ventilator-associated pneumonia (VAP), and one had both
      BSI and VAP. In four others, the organism was isolated from the catheterized
      urinary tract. All VAP and BSI patients were admitted to the Intensive Care Units
      and mechanically ventilated; all had central lines and history of colistin
      therapy during the past 15 days. The common underlying risk factors were
      diabetes, hypertension, and coronary artery disease. Conclusions: C. indologenes
      infections are increasing because of higher use of carbapenems and colistin, to
      which it is intrinsically resistant.

PMID- 30111933
TI  - Cardiopulmonary Arrest and Extracorporeal Membrane Oxygenation: Case Report and
      Review.
AB  - National trends suggest that less than one in four patients experiencing in
      hospital cardiac arrest (IHCA) in the United States survive to discharge. This is
      especially relevant as the rates of IHCA are expected to rise in the years to
      come. Only a modest upward trend in survival to discharge among patients with
      IHCA over the past decade warrants evaluation of novel ideas to improve outcomes
      postcardiopulmonary resuscitation. One such idea is that the use of veno-arterial
      extracorporeal membrane oxygenation (VA-ECMO) to augment standard advanced
      cardiac life support algorithm in patients with an identifiable and reversible
      cause of cardiac arrest would improve survival to discharge. Here, we present the
      case of a patient with refractory ventricular fibrillation arrest who was
      transitioned to VA-ECMO immediately following cardiac catheterization for an
      IHCA.

PMID- 30111934
TI  - A Case of Unusual Occurrence of Nasogastric Tube Feed Coming Through the Chest
      Tube in a 27-Year-Old Polytrauma Patient.
AB  - The provision of early and adequate nutritional support is vital for the
      successful recovery from the trauma in any form. Nutritional support is enteral
      unless specified otherwise as dictated by various benefits of the former.
      Nasogastric tubes provide effective and common mode of enteral feed due to the
      ease of placement and maintenance. To our knowledge, the late presentation of
      diaphragmatic hernia with gastric perforation in a trauma patient leading to feed
      coming through chest tube is very rare of the complications.

PMID- 30111936
TI  - Epidural Hematoma: Vigilance beyond Guidelines.
AB  - Coagulopathy either from the use of anticoagulant, antiplatelet, or thrombolytic
      medications or from underlying medical conditions is considered one of the major
      risk factors for epidural hematoma formation related to epidural catheter
      placement or removal. The American Society of Regional Anesthesia and Pain
      Medicine (ASRA) has laid down guidelines regarding timing of neuraxial blockade
      or removal of neuraxial catheters in patients receiving either antithrombotic or
      thrombolytic therapy. We present a case of acute onset of paraplegia because of
      an epidural hematoma following removal of the epidural catheter in a patient who
      was given the first dose of antithrombotic therapy after the removal of the
      epidural catheter as per the ASRA guidelines. The epidural hematoma was diagnosed
      with an urgent magnetic resonance imaging, and the patient was urgently taken up
      for surgical evacuation of the hematoma. The patient made full recovery over 1
      week period.

PMID- 30111935
TI  - Chondrodysplasia Punctata with Severe Airway Stenosis.
AB  - Chondrodysplasia punctata (CDP) is a group of skeletal dysplasias characterized
      primarily by punctate calcifications in cartilage. It is a rare disease with an
      incidence of 1:100,000 live births. Extensive airway involvement with
      calcification of tracheal, bronchial, and thyroid cartilage in CDP is an
      infrequent finding. We aim to report a case of CDP with characteristic
      radiological features and severe airway involvement.

PMID- 30111937
TI  - Curious Case of Acute Unilateral Deep Vein Thrombosis: May-Thurner Syndrome.
AB  - May-Thurner syndrome (MTS) or iliac vein compression syndrome is an uncommon
      cause of deep venous thrombosis (DVT) of the lower limb occurring, especially on
      the left side. It occurs due to compression of the left common iliac vein by the
      right common iliac artery and occurs predominantly in young females. The
      awareness of such a presentation is essential to guide therapy. We report one
      such unusual case of acute-onset DVT of the left lower limb due to MTS.

PMID- 30111938
TI  - Loss of Guidewire.

PMID- 30111939
TI  - Bloodless Arterial Cannulation Technique.

PMID- 30111940
TI  - Thromboelastographic Analysis of Hemostatic Abnormalities in Dengue Patients
      Admitted in a Multidisciplinary Intensive Care Unit: A Cross-Sectional Study.

PMID- 30111941
TI  - Hippocratic: The Columbus Who Dared to Voyage the "el Fin Del Mundo".

PMID- 30111943
TI  - Caregivers' Difficulty Rating Scale: Development and Initial Validation of a Tool
      to Identify the Unmet Needs of Indian Caregivers.
AB  - Background: Caring for a cancer patient is debilitating for caregivers,
      especially among Indian population, as culturally people prefer to care at home
      than at nursing home. Unavailability of palliative care services and professional
      caregivers adds to the family burden. Objectives: Caregiving difficulties need
      assessment, but cancer-specific burden instruments are rare in the Indian
      context. This article presents development and initial validation of Caregiver's
      Difficulty Rating Scale (CDRS) and highlights the nature of caregiving burden on
      primary caregivers. Methods: A total of 108 items were prepared in English after
      case interviews and reviewing the existing scales for face validity. Experts
      judged the items for content validity, of which 54 items with 100% agreement were
      retained. Forward-backward policy was used for Hindi translation. Reliability
      analysis was performed with thirty respondents. The final scale was administered
      to 100 caregivers of head-and-neck cancer patients for internal consistency and
      item-scale statistics. For construct validity, know-group comparison was made
      using EORTCQOL instrument with caregiver-patients dyads. Results: High
      correlation among the three translated versions (r > 0.76, P < 0.01), Cronbach's
      alpha (0.948), and spilt-half coefficient (0.965) suggested translation
      reliability and scale consistency. Caregiver's burden had significant negative
      correlation with global quality of life of patients (-0.514**). Help for food
      arrangement, managing work-life, and treatment cost were the highly rated
      difficulties. Conclusion: CDRS had fifty items under four dimensions - physical,
      emotional, social, and financial. The scale requires further work on convergent
      and divergent validity and sensitivity to change which are underway. The study
      has implications for respite care. Community engagements and caregivers' support
      group may work as sources of emotional and social support.

PMID- 30111942
TI  - Specialized Palliative Care and the Quality of Life for Hospitalized Cancer
      Patients at a Low-Resource Hospital in India.
AB  - Aim: This study aimed to compare the quality of life (QoL) of cancer patients,
      with an Eastern Cooperative Oncology Group (ECOG) performance of 3-4, in contact
      with or without contact, with a specialized palliative care unit (PCU) at a low
      resource governmental cancer hospital, as well as studying the impact of this
      contact on the QoL in their caregivers. Materials and Methods: Hospitalized
      patients with an ECOG performance of 3 or 4 and their primary caregiver were
      asked to participate in this observational study. Patients in contact with the
      specialized PCU and their closest caregivers formed Group A, while patients and
      families without this contact formed Group B. Contact was mainly one
      consultation. The patients were asked to complete the Palliative Care Outcome
      Scale (POS), and the caregivers were asked to complete the Hospital Anxiety and
      Depression Scale (HADS) and the distress thermometer (DT). Results: There was no
      statistically significant difference between the median POS values of the patient
      groups, neither regarding the total sum nor per any item. There were also no
      statistically significant differences between the median HADS values and median
      DT values when comparing the caregivers to Group A and B. Conclusion:
      Consultation with a specialized PCU at this tertiary referral center did not
      alter the QoL of patients with an ECOG performance of 3-4 nor did it affect the
      psychological well-being of their caregivers. We argue that monitoring prescribed
      treatment and follow-up is a necessary component of PC.

PMID- 30111945
TI  - Stress, Coping, and Lived Experiences among Caregivers of Cancer Patients on
      Palliative Care: A Mixed Method Research.
AB  - Aim: The aim of this study is to assess stress and coping among caregivers of
      cancer patients on palliative care and to acquire a deeper understanding of their
      lived experiences. Materials and Methods: A mixed method study was conducted
      among caregivers of cancer patients on palliative care using mixed method
      approach and triangulation design. Data were gathered using self-administered
      stress rating scale, brief COPE inventory, and structured interview schedule.
      Nested sampling technique was adopted. The sample size for quantitative approach
      was eighty and qualitative approach was eight. Results: The results showed that
      74% of the participants were females and 30% of them belong to the age group
      between 51 and 60 years. Fifty-four percent of them belong to Hindu religion and
      40% were unemployed. Sixty-two percent of the patients were dependent on
      caregivers for all activities of daily living. Assessment of stress revealed that
      82% of the participants had moderate stress and 18% had severe stress.
      Participants adopted both negative and positive coping. There was a significant
      negative correlation (r = -0.722, P = 0.001) between stress and coping. Similar
      findings were also observed in the phenomenological approach. The theme evolved
      was "caring companionship to palliative care." Conclusion: Palliative caregiving
      is stressfull, challenging and can impact the caregiver's physical, emotional,
      psychological, and social well-being. Understanding lived experiences of
      caregivers of cancer patients on palliative care is important for the health
      professionals to improve the support, guidance, and education given to the
      caregivers of cancer patients on palliative care.

PMID- 30111946
TI  - Perspectives of Glioblastoma Patients on Death and Dying: A Qualitative Study.
AB  - Background: Glioblastoma (GBM) is a terminal illness and associated with poor
      prognosis. Brain cancer creates significant traumatic effects including death and
      dying fears not only on patients but also in Asia's tightly knitted families.
      Very few studies made attempt to elicit the death and dying issues among brain
      cancer patients. Therefore, the study aimed to explore the patient's perspectives
      on death and dying among GBM patients during hospitalization. Methodology: The
      study used qualitative approach. Purposive sampling was used to enroll 31
      consented patients for in depth interviews. The in-depth interviews were guided
      by pre-designed open ended guidelines and took 45 min to 1 h. All interviews were
      conducted in the private room in the hospital. Interviews were manually
      documented soon after the interview. Thematic analysis was used to generate
      themes. R (QOL) software was used for data analysis. Results: Four themes were
      emerged from the analysis; (i). Understanding about illness (ii). Personal views
      and feelings on death and dying (iii). Coping with fear of death and dying (iv).
      Need for early preparation to face death and dying fears. Conclusion:
      Psychosocial interventions on early death preparation programs are recommended
      for GBM patients in the in-patient care. Yet, it should be handled carefully and
      sensitively, otherwise, it creates more psychological and emotional harm than the
      illness per se.

PMID- 30111944
TI  - Palliation of Brain Metastases: Analysis of Prognostic Factors Affecting Overall
      Survival.
AB  - Context: Brain metastasis is one of the most feared complications of cancer that
      poses significant mortality and morbidity in patients with advanced cancer. The
      incidence is rising because of greater use of magnetic resonance imaging and
      spectroscopy; and increased survival from recent advances in immunotherapy and
      modern radiotherapy techniques. Despite all, the prognosis remains poor. Aims:
      This study aimed to analyze prognostic factors and overall survival in patients
      with brain metastases. Subjects and Methods: A total of 145 patients were
      analyzed from July 2014 to June 2015 for various prognostic factors
      prospectively. Survival analysis was done using Kaplan-Meier curve. Results: The
      median overall survival was 6 months, while 1- and 2-year survival rates were
      8.3% and 1.4%, respectively. Median survival was highest with surgery followed by
      radiotherapy (11 months). Whole-brain radiotherapy (WBRT) significantly improved
      the survival (P = 0.006). The most common primary was lung cancer (58%) and the
      most common histology was adenocarcinoma (36%). Most patients (38%) were
      diagnosed upfront with brain metastases. Most of the lesions were multiple (80%)
      and located in cerebrum (58%). Survival was significantly improved with female
      gender (P = 0.003), Eastern Cooperative Oncology Group performance status (PS) 0
      2 (P = 0.006), breast primary (P = 0.004), time lag of >6 months (P < 0.001),
      solitary lesion (P = 0.002), and controlled primary (P = 0.017). Conclusions:
      WBRT remains the cornerstone of the management of brain metastases. The present
      study concludes that the survival of patients with brain metastases is
      significantly improved with female gender, good PS, primary breast cancer, time
      lag of >6 months between diagnosis of the primary tumor and development of brain
      metastases, solitary lesion, and controlled primary tumor.

PMID- 30111948
TI  - End-of-life Decision-making for People in a Minimally Conscious State: A Review
      of the Application of the Mental Capacity Act 2005.
AB  - The last 15 years has seen clarification of the terminology used to describe
      prolonged disorders of consciousness within the United Kingdom leading to the
      emergence of a new diagnosis - minimally conscious state (MCS) in 2002. MCS is
      distinct from vegetative states, in that a person demonstrates wakefulness with
      some degree of minimal awareness. The Mental Capacity Act (MCA) 2005 in England
      and Wales provides a legal framework for assessing an individuals' capacity to
      make decisions for themselves. The Act also authorizes others to make decisions
      on behalf of an individual who is assessed as lacking capacity in their best
      interests. The Act has an accompanying Code of Practice which provides guidance
      and a best interests "test" to be applied when assessing best interests. Since
      the advent of the Act, approximately two cases each year go to the Court of
      Protection for final decisions regarding end-of-life care in people in an MCS.
      Currently, any decision involving the withdrawal of clinically assisted nutrition
      and hydration (CANH) for people in an MCS must be referred to the court. In each
      case, the courts analyze the application of the Act which has become central in
      the court's decision-making process, particularly when assessing best interests.
      This article provides an overview of key MCA sections applied in such end-of-life
      MCS cases and reviews seminal cases elucidating how the Act has been applied. It
      further describes the evolution of how courts have interpreted the doctrine of
      best interests when considering withholding or withdrawing CANH and other life
      sustaining treatments.

PMID- 30111947
TI  - Quality of Life and Neuropathic Pain in Hospitalized Cancer Patients: A
      Comparative Analysis of Patients in Palliative Care Wards Versus Those in General
      Wards.
AB  - Context: While the survival of cancer patients is prolonged due to the
      development of new treatment strategies and advancing technologies, the
      prevalence of symptoms such as neuropathic pain affecting the quality of life is
      also increasing. Aims: The aim of this study is to determine the relationship
      between neuropathic pain (NP) and quality of life in hospitalized cancer patients
      and to compare patients in general wards and those in palliative care wards in
      terms of NP and quality of life. Subjects and Methods: A total of 156 patients,
      53 cancer patients hospitalized in the palliative care unit and 103 cancer
      patients hospitalized in general wards, were included in the study. The Douleur
      Neuropathic 4 test was used for NP assessment, and the Edmonton Symptom
      Assessment System (ESAS), Hospital Anxiety and Depression Scale (HAD), Brief
      Fatigue Inventory (BFI), and Short Form of Brief Pain Inventory (SF-BPI) were
      used for assessing pain characteristics and their effects on quality of life.
      Results: NP was present in 39.7% of cases and nociceptive pain (NP) was present
      in 32.7% of cases. There were no complaints of pain 27.6% of cases. The patients
      with no pain complaint were excluded, 54.9% of the patients had NP and 45.1% had
      NS. The scores of BFI, HAD-depression, ESAS overall, and ESAS tiredness were
      significantly lower in patients with NP treated general wards compared to
      patients with NP in the palliative care wards (P < 0.05). Cancer patients with NP
      in general wards had significantly higher scores of SF-BPI effect, SF-BPI
      severity, ESAS overall, ESAS pain, ESAS tiredness, ESAS nausea, ESAS appetite,
      and ESAS well-being as compared to those of general cancer patients with NS (P <
      0.05). Conclusions: Since there was a homogeneous distribution among the groups
      in terms of both cancer treatment and pain management, we directly related the
      deterioration of the patients' quality of life to NP.

PMID- 30111949
TI  - Unmet Needs for Palliation in Fibrotic Interstitial Lung Disease.
AB  - Chronic fibrotic interstitial lung disease (ILD) forms a substantial proportion
      of disabling lung diseases and leads to significant morbidity and mortality. The
      mortality of these patients when admitted to the Intensive Care Unit with acute
      respiratory worsening requiring mechanical ventilation can reach up to 90%.
      Indian law does not allow the physician to make the final decision about
      mechanical ventilation, we are forced to follow the wishes of the family despite
      knowing the extremely poor outcome of aggressive intervention and invasive
      ventilation. Patients more often become ventilator dependent and do not gain much
      regarding the quality of life with mechanical ventilation. Hence, there is a
      desperate need for palliative support for these patients with advance care
      planning to reduce the suffering of these patients toward the end of life. The
      article describes various methods by which the decision making process of
      mechanical ventilation could be made simpler and acceptable to the patient and
      the families of fibrotic Interstitial lung disease patients and also the dilemma
      faced by chest physician in India with virtually no prior end of life planning
      and no clear guidelines on ventilation when it comes to palliation of patients
      with advanced ILD.

PMID- 30111950
TI  - The PEP Project - Synergistic Community Based Action in Prevention, Early
      Detection and Palliative Care, to Impact the Cancer Burden in India.
AB  - With unprecedented surge in the incidence and prevalence of cancer in India, it
      has become imperative to strengthen the workforce for all the domains of cancer
      care. A large proportion of the activity required for prevention as well as for
      palliation, lie outside of tertiary institutions, in the community. Palliative
      care (PC) as a field is expanding exponentially across the country and the
      service providers often engage and work actively within the local community in
      their region. This article describes the scope for reducing the cancer burden in
      the community, through capacity building of community based PC healthcare
      functionaries in the domains of Prevention, and Early detection of common cancers
      along with Palliative care - the PEP domains. It suggests aligning and enhancing
      the workforce already active within the community for PC, for screening, and if
      feasible, for early detection of common cancers. The article describes
      possibilities of initiating PEP activities and offers a set of screening
      questionnaire that may be used when engaged with family/ community setting. The
      aim is to integrate the activities done, to detect the need for palliative care
      in a family / community, with that required to detect need for evaluation of most
      common cancers- oral, breast and cervix. The PEP concept may be adapted to
      different levels, based on the team presence in the communities, degree of
      engagement, and availability of trainers and healthcare personnel.

PMID- 30111951
TI  - Utilizing Yoga in Oncologic Patients Treated with Radiotherapy: Review.
AB  - Purpose: Several trials on noncancer population indicate that yoga is associated
      with meaningful clinical effects. This study evaluated the physical and
      psychosocial outcomes of yoga in oncologic patients treated with radiotherapy.
      Methods: We focused on a research through Cochrane Register of Controlled Trials
      (CENTRAL), BioMed Central, and MEDLINE studies up to May 2017. Results: Yoga was
      found to have a substantial benefit in cancer patients' distress, anxiety, and
      depression. It also demonstrated a moderate impact on fatigue and emotional
      function and a small and insignificant effect on functional well-being and sleep
      disturbances. As far as the effects on psychological outcomes are concerned,
      there was insufficient evidence. Conclusions: This systematic review of
      randomized controlled trials showed that yoga has strong beneficial effects on
      oncologic patients' quality of life. Results of the current review must be
      interpreted with caution due to the relative small sample sizes of most of the
      included studies, while a prospective randomized study stands in need for the
      confirmation of our results.

PMID- 30111952
TI  - Palliative Mastectomy Revisited.
AB  - Couple of decades ago, Palliative Mastectomy for locally advanced breast cancers
      was common, if not frequent surgical procedure in the surgical armamentarium. The
      advent of better understanding of tumor biology and better multidisciplinary
      management has certainly narrowed down its role. However there are situations
      where it is still a potent option. In the subset of patients where palliative
      mastectomy is to be performed, it is important to aim for clear surgical margins,
      with good clearance at the third dimension, i.e. the tumor base. Surgeons with
      adequate experience of breast cancer surgeries should perform the procedure to
      achieve intended palliation.

PMID- 30111953
TI  - Organ Donation in Pediatric Patients with Severe Anoxic Brain Injury.
AB  - Anoxic brain injury in children is a rare and devastating occurrence. Families
      are shocked by the unexpected nature of their child's neurologic injury, which
      may be the result of a sudden and prolonged cardiac arrest. Organ donation in
      these children is subject to much discussion and controversy. Recently, we
      encountered three pediatric patients with anoxic brain damage who progressed to
      brain death within a few days of admission. Pediatric palliative care was
      involved from the time of arrival to the hospital in all the patients. The team
      served as a critical conduit to support families and helped in managing end-of
      life decisions including organ donation. All three families consented to organ
      donation. We discuss here the patients, the palliative care involvement, and the
      factors responsible for successful donation.

PMID- 30111954
TI  - Asymptomatic Cardiac Metastasis in a Diagnosed Case of Squamous Cell Carcinoma of
      the Middle Third of Esophagus.
AB  - A lady walks in with complaints of dysphagia mostly to solids to begin with and
      gradually progressive to liquids requiring naso-gastric tube feeding, with
      history of vomiting after taking food and weight loss of 20kilograms over
      2months. Upper gastrointestinal endoscopy showed an ulceroproliferative growth
      starting at 28cms from the central incisor and extending upto 36 cms with luminal
      compromise. Biopsy from the lesion was found to be moderately differentiated
      squamous cell carcinoma. As part of metastatic work-up a PET-CT (Figure 1 shows
      lesion in the left ventricle) was done which revealed a metabolically active
      lesion involving the lower third of esophagus and a metabolically active lesion
      in the wall of the left ventricle which was the only site of metastatic
      diseae(Figure 2. Maximum intensity projection). Further investigations were done
      for characterisation of the cardiac lesion. 2-D Echo cardiography was done and
      was normal with an ejection fraction of 60%. A cardiac MRI was done which showed
      a soft tissue mass in the wall of the left ventricle which was isointense with
      normal myocardium and hyperintense on double inversion recovery sequence which
      measured 3.2 x 3 cms with post contrast enhancement. She was planned for
      palliative radiotherapy. A total dose of 30Gy in 10 fractions over 2 weeks was
      delivered. She tolerated the treatment well with Grade I mucositis (as per RTOG
      grading) and on follow-up after 4 weeks she had 40% relief in dysphagia and could
      take semi-solid food with little difficulty.

PMID- 30111955
TI  - Radiation-Induced Neuropsychiatric Manifestations in a Patient with Brain
      Metastasis: A Diagnostic and Therapeutic Challenges for Consultation-Liaison
      Psychiatrist.
AB  - The aim of this case report is to highlight diagnostic and therapeutic challenges
      for consultation-liaison psychiatrist in the case of radiation-induced
      neuropsychiatric syndrome. We report the case of a 61-year-old man presented with
      neurological and psychiatric manifestations following the radiation therapy for
      non-small cell lung carcinoma with brain metastasis. We have briefly reviewed and
      discussed the risk factors, clinical features, diagnostic, therapeutic, and
      preventive aspect of radiation-induced neuropsychiatric manifestations.

PMID- 30111956
TI  - Olanzapine in the Treatment of Refractory Nausea and Vomiting in Palliative Care
      Settings.
AB  - The patients often present to palliative care with intractable nausea and
      vomiting. This may reduce the effectiveness of oral drugs and significantly
      affects the quality of life of these patients. Despite multiple drugs available
      for treatment, it is often difficult to control the symptoms. Olanzapine is an
      atypical antipsychotic and acts on multiple receptors and may help in treating
      vomiting in a patient with advanced malignancy. We report a case of gallbladder
      carcinoma who presented to us with intractable vomiting which was not relieved
      with a combination of traditional antiemetics but showed marked improvement with
      olanzapine.

PMID- 30111957
TI  - Bradycardia with Syncope in Carotid Sinus Syndrome: A Rare Case Report in
      Palliative Care.
AB  - Emergencies in palliative care need to be defined by the potential distress that
      a clinical issue raises for a person. A 58-year-old male with carcinoma vallecula
      referred for palliative care presented with recurrent syncopal attacks. On
      examination, a swelling at the left angle of mandible pressing on the carotid
      sinus was detected. A clinical diagnosis of carotid sinus syndrome was made,
      which is an exaggerated response to carotid sinus baroreceptor stimulation and
      results in dizziness or syncope from transient diminished cerebral perfusion.
      Rapid identification and judicious interventions in time (cardiac consultation,
      intravenous atropine 0.5 mg, and temporary pacemaker implantation) were able to
      manage a potentially correctable cardiovascular emergency in his case.

PMID- 30111958
TI  - Massive Lymphedema Necessitating Disarticulation of Shoulder Joint Following
      Treatment for Carcinoma Breast.
AB  - We report a case of massive upper-limb edema necessitating disarticulation, in a
      cancer survivor who tended to ignore instructions regarding preventive exercises
      since 2002 after completion of her treatment for breast cancer. However, she was
      in a family situation where she was constrained to physically involve in daily
      chores. Consequently, she presented 14 years later with a lymphedematous arm
      which weighed over 31 kg, necessitating disarticulation. We highlight the role of
      preventive exercises in postmastectomy patients and also the efficacy of
      continuous nerve block techniques in preventing the development of phantom limb
      pain in cases of disarticulation and amputation. The role of family support for a
      working female cancer survivor in a country like India needs to be addressed. We
      salute her commitment to her family as also her grit and determination. Shoulder
      disarticulation was the last choice for this woman. We also want to highlight the
      role of the community in monitoring and preventing such disasters.

PMID- 30111959
TI  - Are We Missing Out on Something?
AB  - Suicide risk is very high in the patients suffering from advanced cancer. Around
      60% of patients with advanced cancer suffer from cancer related pain and this
      further accentuates the risk of psychiatric disorders as well as suicide. A fifty
      year old male who was a known case of carcinoma of floor of mouth, post
      chemotherapy and post radiotherapy came in the outpatient clinic with complains
      of throat pain which increased on swallowing. On further probing, it was
      revealed, that he consumed poison in the recent past while being agitated and
      upset with the severe throat pain. The recent radiotherapy had only made the pain
      worse. Cancer pain is an important symptom which should be adequately addressed
      while reviewing patients in the palliative care / oncologist clinic.

PMID- 30111960
TI  - Tanezumab: Finally a Monoclonal Antibody for Pain Relief.

PMID- 30111961
TI  - Palliative Dermatology.

PMID- 30111962
TI  - Could Art Therapy Reduce the Death Anxiety of Patients with Advanced Cancer? An
      Interesting Question that Deserves to be Investigated.

PMID- 30111963
TI  - An Internal Medicine Residents' Perspective on End-of-life Discussions.

PMID- 30111964
TI  - General practitioners in oncology: their valuable role throughout the cancer care
      trajectory.

PMID- 30111965
TI  - Engaging cancer patients in clinical practice guideline development: a pilot
      study.
AB  - Background: Patient engagement is a key quality component of cancer guideline
      development; however, the optimal strategy for engaging patients in guideline
      development remains unclear. The feasibility and efficacy of two patient
      engagement models was tested by Cancer Care Ontario's cancer guideline
      development program, the Program in Evidence-Based Care (pebc). Methods: In model
      1, patients participated in the guideline development process as active members
      of a working group. In model 2, patients formed a separate consultation group to
      review project plans and recommendations generated by multiple working groups.
      Training included online resources (model 1) and an in-person orientation (model
      2). The pebc's standard patient engagement process acted as a control. The study
      was conducted for 1 year. Surveys measured the satisfaction of patients and
      members of the guideline working groups with the process and the outcome of each
      model. Results: Three guideline projects used model 1 to engage patients, six
      projects used model 2 to receive feedback, and one project was used as a control
      group (14 patients total). Most participants, whatever the model, reported
      satisfaction with their experience. Key challenges to implementation included
      patient recruitment and long wait times between meetings (model 1), and
      difficulty focusing on the discussion topic and poor meeting attendance on the
      part of patients (model 2). Conclusions: The pilot study demonstrated that,
      although both models are feasible and effective for the engagement of patients in
      cancer guideline development, modifications are required to optimize their
      continued interest. The pebc will use the study results to inform the
      implementation of a patient engagement strategy for its program.

PMID- 30111966
TI  - Understanding the reasons for provincial discordance in cancer drug funding-a
      survey of policymakers.
AB  - Background: Cancer drug-funding decisions between provinces shows discordance.
      The pan-Canadian Oncology Drug Review (pcodr) was implemented in 2011 partly to
      address uneven drug coverage and lack of transparency in the various provincial
      cancer drug review processes in Canada. We evaluated the underlying reasons for
      ongoing provincial discordance since the implementation of pcodr. Methods:
      Participation in an online survey was solicited from participating provincial
      ministries of health (mohs) and cancer agencies (cas). The 4-question survey
      (with both multiple-choice and free-text responses) was administered between 4
      March 2015 and 1 April 2015, inclusive. Anonymity was ensured. Descriptive
      statistics were used to evaluate responses. Results: Data were available from 9
      provinces (all Canadian provinces except Quebec), with a response rate of 100%.
      The 12 responses received each came from a senior policymaker with more than 5
      years' experience in cancer drug funding decision-making (5 from mohs, 7 from
      cas). Responses for 3 provinces came from both a moh representative and a ca
      representative. The most common reason for funding a drug not recommended by
      pcodr was political pressure (64%). The most common reason not to fund a drug
      recommended by pcodr was budget constraints (91%). The most common reason for a
      province to fund a drug before completion of the pcodr review was also political
      pressure (57%). Conclusions: Political pressure and budgetary constraints
      continue to affect equity of access to cancer drugs for patients throughout
      Canada.

PMID- 30111970
TI  - Unnecessary variation in practice: how to improve cancer care through pragmatic
      trials.

PMID- 30111969
TI  - Endocrine therapy for breast cancer in the primary care setting.
AB  - : The treatment of hormone-positive breast cancer (bca) is a rapidly evolving
      field. Improvement in the understanding of the mechanisms of action and
      resistance to anti-hormonal therapy has translated, in the past decade, into
      multiple practice-changing clinical trials, with the end result of increased
      survivorship for patients with all stages of hormone-positive cancer. The primary
      care physician will thus play an increasing role in the routine care,
      surveillance, and treatment of issues associated with anti-hormonal therapy. The
      aim of the present review was to provide a focused description of the issues
      relevant to primary care, while briefly highlighting recent advances in the field
      of anti-hormonal therapy. Key Points: ? Hormone-positive bca is the most
      prevalent form of bca and, compared with the other subtypes, is usually
      associated with better survival.? Survivorship has significantly increased for
      all stages of hormone-positive bca, making the primary care physician a key
      player in the care of affected patients.? The two most common classes of anti
      hormonal agents used in these patients are selective estrogen receptor modulators
      and aromatase inhibitors. Each class of medication is associated with signature
      side effects.? Within the past decade, multiple novel estrogen receptor blockers
      (for example, fulvestrant) and agents aimed at circumventing resistance to
      endocrine therapy [inhibitors of cyclin-dependent kinase 4/6 and of mtor (the
      mechanistic target of rapamycin)] have gained clinical ground. Understanding
      their side effects will be increasingly relevant to primary care physicians.?
      Multidisciplinary care is always encouraged in the care of cancer patients
      receiving anti-hormonal therapy.

PMID- 30111968
TI  - Report from the 19th annual Western Canadian Gastrointestinal Cancer Consensus
      Conference; Winnipeg, Manitoba; 29-30 September 2017.
AB  - The 19th annual Western Canadian Gastrointestinal Cancer Consensus Conference
      (wcgccc) was held in Winnipeg, Manitoba, 29-30 September 2017. The wcgccc is an
      interactive multidisciplinary conference attended by health care professionals
      from across Western Canada (British Columbia, Alberta, Saskatchewan, and
      Manitoba) who are involved in the care of patients with gastrointestinal cancer.
      Surgical, medical, and radiation oncologists; pathologists; radiologists; and
      allied health care professionals participated in presentation and discussion
      sessions for the purpose of developing the recommendations presented here. This
      consensus statement addresses current issues in the management of colorectal
      cancer.

PMID- 30111967
TI  - Eastern Canadian Colorectal Cancer Consensus Conference 2017.
AB  - The annual Eastern Canadian Gastrointestinal Cancer Consensus Conference 2017 was
      held in St. John's, Newfoundland and Labrador, 28-30 September. Experts in
      radiation oncology, medical oncology, surgical oncology, and cancer genetics who
      are involved in the management of patients with gastrointestinal malignancies
      participated in presentations and discussion sessions for the purpose of
      developing the recommendations presented here. This consensus statement addresses
      multiple topics in the management of gastric, rectal, and colon cancer, including
      ? identification and management of hereditary gastric and colorectal cancer
      (crc);? palliative systemic therapy for metastatic gastric cancer;? optimum
      duration of preoperative radiation in rectal cancer-that is, short- compared with
      long-course radiation;? management options for peritoneal carcinomatosis in crc;?
      implications of tumour location for treatment and prognosis in crc; and? new
      molecular markers in crc.

PMID- 30111971
TI  - Evaluation of the delivery of survivorship care plans for South Asian female
      breast cancer survivors residing in Canada.
AB  - Background: This paper focuses on phase iii of a study evaluating the development
      and implementation of a survivorship care plan (scp) that could ultimately
      improve post-treatment quality of life for South Asian (sa) breast cancer
      survivors (bcss). Evaluating the utility of the scp was important to understand
      how sociocultural influences might affect uptake of the scp by sa bcss,
      especially as they transition from treatment to community care. Methods: Post
      treatment discharge planning using an individualized scp at discharge for sa
      female breast cancer patients with stage i or ii disease was offered as a pilot
      service to oncologists at BC Cancer's Fraser Valley and Abbotsford centres. A
      longitudinal study using a mixed-methods approach was used to evaluate the
      utility of that service at 1 year after discharge. Results: Participants (n = 16)
      completed a survey about their scp delivery experience, and a 1-year post
      implementation survey about the scp content and its utility. Most participants
      reported the discharge appointments to be extremely or very helpful with respect
      to post-treatment care questions. All have visited their family physicians for
      follow-up as recommended. The three major sources of support were family, faith,
      and family physician. Qualitative responses from the health care professionals
      who developed or implemented the scps identified two challenges in scp delivery:
      engaging patients or family members in relationship, and translating key
      information through interpreters. Conclusions: It is important to evaluate the
      utility of scps for sa female survivors, who might differ from the general bcs
      population because of a different understanding of the disease; language
      barriers; strong influence of family members; societal stigmas; and personal,
      social, cultural, and religious beliefs and values. A formal nurse-led discharge
      appointment with discussions about follow-up care and an individualized scp
      outlining the short- and long-term effects of treatment are recommended.
      Particular attention has to be paid to the practical and psychosocial needs of sa
      bcss and their supporting family members.

PMID- 30111972
TI  - Complementary and alternative medicine use in patients before and after a cancer
      diagnosis.
AB  - Background: Cancer patients are increasingly seeking out complementary and
      alternative medicine (cam) and might be reluctant to disclose its use to their
      oncology treatment team. Often, cam agents are not well studied, and little is
      known about their potential interactions with chemotherapy, radiation therapy, or
      biologic therapies, and their correlations with outcomes. In the present study,
      we set out to determine the rate of cam use in patients receiving treatment at a
      Northern Ontario cancer centre. Methods: Patients reporting for treatment at the
      Northeast Cancer Centre (necc) in Sudbury, Ontario, were asked to complete an
      anonymous questionnaire to assess cam use. Changes in cam use before, compared
      with after, diagnosis were also assessed. Results: Patients in Northern Ontario
      reported significant cam use both before and after diagnosis. However, as a
      function of the cam type, cam use was greatly enhanced after cancer diagnosis.
      For example, the number of patients who reported use of biologic products
      increased to 51.8% after a cancer diagnosis from 15.6% before a cancer diagnosis.
      Patients reported much smaller changes in the use of alternative medical systems
      or spiritual therapy after diagnosis. Vitamin use was reported by 66% of
      respondents, and the number of different cams used correlated significantly with
      the reported number of vitamins used. Conclusions: Use of cam, particularly
      biologic products, increased significantly after a cancer diagnosis. Further
      studies are required to examine the effect of cam use on the efficacy and safety
      of cancer therapies.

PMID- 30111973
TI  - Real-world patient- and caregiver-reported outcomes in advanced breast cancer.
AB  - Background: Advanced breast cancer (abc) represents a substantial burden for
      patients and caregivers. In the present study, we aimed to estimate quality of
      life (qol), utility, productivity loss, pain, health care resource utilization,
      and costs for patients with abc, and qol, utility, and productivity loss for
      their caregivers. Methods: This multicentre prospective non-interventional study
      was conducted in Canada. Eligible participants were postmenopausal women with
      estrogen receptor-positive, her2-negative unresectable abc and their caregivers.
      Validated questionnaires were used to measure qol, utility, productivity loss,
      and pain. Patients and caregivers were classified into 4 health states typically
      used in oncology economic modelling: first-line progression-free (1l-pf), first
      line progressive disease (1l-pd), second- or subsequent-line progression-free
      (>=2l-pf), and second- or subsequent-line progressive disease (>=2l-pd). Results:
      Most patients and caregivers accepted to participate, with total recruitment of
      202 patients and 78 caregivers. Compared with patients in pf, patients in pd had
      lower mean qol scores (52.9 +/- 29.9 for 1l-pd vs. 68.2 +/- 23.2 for 1l-pf, and
      54.0 +/- 23.6 for >=2l-pd vs. 66.0 +/- 22.1 for >=2l-pf), lower mean utility
      values (0.64 +/- 0.22 for 1l-pd vs. 0.73 +/- 0.20 for 1l-pf, and 0.65 +/- 0.25
      for >=2l-pd vs. 0.74 +/- 0.18 for >=2l-pf), and greater productivity loss (39.4
      +/- 27.7 for 1l-pd vs. 27.5 +/- 30.1 for 1l-pf, and 37.6 +/- 29.2 for >=2l-pd vs.
      32.0 +/- 29.0 for >=2l-pf). Compared with caregivers of patients in pf,
      caregivers of patients in pd had lower qol scores and utility values, and greater
      productivity loss. Conclusions: Study results indicate that, for patients and
      caregivers, pd health states are associated with a deterioration of qol and
      utility and a decrease in productivity in both 1l and >=2l.

PMID- 30111974
TI  - Are clinical trial eligibility criteria an accurate reflection of a real-world
      population of advanced non-small-cell lung cancer patients?
AB  - Background: Advanced non-small-cell lung cancer (nsclc) represents a major health
      issue globally. Systemic treatment decisions are informed by clinical trials,
      which, over years, have improved the survival of patients with advanced nsclc.
      The applicability of clinical trial results to the broad lung cancer population
      is unclear because strict eligibility criteria in trials generally select for
      optimal patients. Methods: We performed a retrospective chart review of all
      consecutive patients with advanced nsclc seen in outpatient consultation at our
      academic institution between September 2009 and September 2012, collecting data
      about patient demographics and cancer characteristics, treatment, and survival
      from hospital and pharmacy records. Two sets of arbitrary trial eligibility
      criteria were applied to the cohort. Scenario A stipulated Eastern Cooperative
      Oncology Group performance status (ecog ps) 0-1, no brain metastasis, creatinine
      less than 120 MUmol/L, and no second malignancy. Less-strict scenario B
      stipulated ecog ps 0-2 and creatinine less than 120 MUmol/L. We then used the two
      scenarios to analyze treatment and survival of patients by trial eligibility
      status. Results: The 528 included patients had a median age of 67 years, with 55%
      being men and 58% having adenocarcinoma. Of those 528 patients, 291 received at
      least 1 line of palliative systemic therapy. Using the scenario A eligibility
      criteria, 73% were trial-ineligible. However, 46% of "ineligible" patients
      actually received therapy and experienced survival similar to that of the
      "eligible" treated patients (10.2 months vs. 11.6 months, p = 0.10). Using the
      scenario B criteria, only 35% were ineligible, but again, the survival of treated
      patients was similar in the ineligible and eligible groups (10.1 months vs. 10.9
      months, p = 0.57). Conclusions: Current trial eligibility criteria are often
      strict and limit the enrolment of patients in clinical trials. Our results
      suggest that, depending on the chosen drug, its toxicities and tolerability,
      eligibility criteria could be carefully reviewed and relaxed.

PMID- 30111977
TI  - Adherence to guidelines in requesting Oncotype DX in a publicly funded health
      care system.
AB  - Background: Oncotype dx [odx (Genomic Health, Redwood City, CA, U.S.A.)] is an
      approved prognostic tool for women with node-negative, hormone receptor-positive,
      her2-negative breast cancer. Because of cost, optimal use of this test is
      crucial, especially in a publicly funded health care system. We evaluated
      adherence with our provincial guidelines for odx requests, the management of
      patients with an intermediate recurrence score (rs), and the cost impact of odx.
      Methods: This retrospective study included 201 consecutive patients with an odx
      request from two university institutions in Quebec between May 2012 and December
      2014. Concordance with provincial guidelines was estimated, with its 95%
      confidence interval (ci). For patients with an intermediate rs, factors
      influencing the final treatment decision were assessed. The cost impact of odx
      was derived from the proportion of patients for whom chemotherapy was not
      recommended. Results: In 93.0% of patients (95% ci: 89.5% to 96.6%), odx was
      ordered according to guidelines. The concordance was similar in both institutions
      (92.7%; 95% ci: 88.1% to 97.3%; and 93.6%; 95% ci: 88.2% to 99.0%). In 112
      (55.7%), 78 (38.8%), and 9 (4.5%) patients, the rs suggested low, intermediate,
      and high risk respectively. In the intermediate-risk group, most patients (n =
      58, 74.4%) did not receive chemotherapy, mainly because of patient preference and
      the absence of a clear proven benefit. Savings of CA$100,000 for the study period
      (2.5 years) were estimated to be associated with odx use. Conclusions: In our
      experience, the use of odx was concordant with published recommendations and had
      a positive cost impact.

PMID- 30111975
TI  - Optimizing vascular access for patients receiving intravenous systemic therapy
      for early-stage breast cancer-a survey of oncology nurses and physicians.
AB  - Background: Despite advances in systemic therapy choices for patients with early
      stage breast cancer, optimal practices for intravenous (IV) access remain
      unknown. That lack of knowledge holds particularly true for the use of central
      venous access devices (cvads) such as peripherally inserted central catheters
      (piccs) and implanted vascular access devices (ports). Methods: Using a survey of
      Canadian oncologists and oncology nurses responsible for the care of breast
      cancer patients, we evaluated current access practices, perceptions of
      complications, and perceptions of risk, and we estimated complication rates and
      evaluated perceived risk factors for lymphedema. Results: Survey responses were
      received from 25 physicians and 57 oncology nurses. Administration of trastuzumab
      or an anthracycline was associated with a higher likelihood of a cvad being
      recommended. Other factors associated with recommendation of a cvad included
      prior difficult IV access and a recommendation from the chemotherapy nurse.
      Although the complication rates perceived to be associated with the use of piccs
      and ports remained high, respondents felt that cvads might improve patient
      quality of life. Risk factors perceived to be associated with the risk of
      lymphedema were axillary lymph node dissection, radiation to the axilla, and line
      associated infection. Factors known to be unrelated to lymphedema risk
      (specifically, blood draws and blood pressure measurement) continue to be
      perceived as posing a higher risk. Conclusions: Despite widespread use of
      chemotherapy for patients with breast cancer, the type of venous access used for
      treatment varies significantly, as do perceptions about the risks of cvad use and
      the risk for lymphedema development. Further prospective studies are needed to
      identify best-practice strategies.

PMID- 30111976
TI  - Perceptions of vascular access for intravenous systemic therapy and risk factors
      for lymphedema in early-stage breast cancer-a patient survey.
AB  - Background: The choice of vascular access for systemic therapy administration in
      breast cancer remains an area of clinical equipoise, and patient preference is
      not consistently acknowledged. Using a patient survey, we evaluated the patient
      experience with vascular access during treatment for early-stage breast cancer
      and explored perceived risk factors for lymphedema. Methods: Patients who had
      received systemic therapy for early-stage breast cancer were surveyed at 2
      Canadian cancer centres. Results: Responses were received from 187 patients
      (94%). The route of vascular access was peripheral intravenous line (IV) in 24%,
      a peripherally inserted central catheter (picc) in 42%, and a surgically inserted
      central catheter (port) in 34%. Anthracycline-based regimens were associated with
      a greater use of central vascular access devices (cvads- that is, a picc or port;
      86/97, 89%). Trastuzumab use was associated with greater use of ports (49/64,
      77%). Although few patients (7%) reported being involved in the decisions about
      vascular access, most were satisfied or very satisfied (88%) with their access
      type. Patient preference centred mainly on avoiding delays in the initiation of
      chemotherapy. Self-reported rates of complications (183 evaluable responses) were
      infiltration with peripheral IVs (9/44, 20%), local skin infections with piccs
      (7/77, 9%), and thrombosis with ports (4/62, 6%). Perceived risk factors for
      lymphedema included use of the surgical arm for blood draws (117/156, 75%) and
      blood pressure measurement (115/156, 74%). Conclusions: Most patients reported
      being satisfied with the vascular access used for their treatment. Improved
      education and understanding about the evidence-based requirements for vascular
      access are needed. Perceived risk factors for lymphedema remain variable and are
      not evidence-based.

PMID- 30111978
TI  - Baseline Edmonton Symptom Assessment System and survival in metastatic renal cell
      carcinoma.
AB  - Background: Baseline symptom burden as measured using the Edmonton Symptom
      Assessment System (esas), a patient-reported, validated, and reliable tool
      measuring symptom severity in 9 separate domains, might yield prognostic
      information in patients receiving treatment for metastatic renal cell carcinoma
      (mrcc) and might add to the existing prognostic models. Methods: In this
      retrospective single-centre cohort study, we included patients receiving first
      line sunitinib therapy for mrcc between 2008 and 2012. Baseline variables
      included information relevant to the pre-existing prognostic models and pre
      treatment esas summation scores (added together across all 9 domains), with
      higher scores representing greater symptom burden. We used Kaplan-Meier curves
      and Cox regression modelling to determine if symptom burden can provide
      prognostic information with respect to overall survival. Results: We identified
      68 patients receiving first-line therapy for mrcc. Most had intermediate- or poor
      risk disease based on both the Memorial Sloan Kettering Cancer Center (mskcc) and
      the International Metastatic Renal Cell Carcinoma Database Consortium (imdc)
      models. The median baseline esas summation score was 16 (range: 6-57). In
      univariable analysis, the hazard ratio for overall survival was 1.270 (p =
      0.0047) per 10-unit increase in summation esas. In multivariable analysis, the
      hazard ratio was 1.208 (p = 0.0362) when controlling for mskcc risk group and
      1.240 (p = 0.019) when controlling for imdc risk group. Conclusions: Baseline
      symptom burden as measured by esas score appears to provide prognostic
      information for survival in patients with mrcc. Those results should encourage
      the investigation of patient-reported symptom scales as potential prognostic
      indicators for patients with advanced cancer.

PMID- 30111982
TI  - Erratum: Cost-effectiveness of everolimus for the treatment of advanced
      neuroendocrine tumours of gastrointestinal or lung origin in Canada.
AB  - [This corrects the article on p. 32 in vol. 25, PMID: 29507481.].

PMID- 30111983
TI  - Bad science: International organizations and the indirect power of global
      benchmarking.
AB  - The production of transnational knowledge that is widely recognized as legitimate
      is a major source of influence for international organizations. To reinforce
      their expert status, international organizations increasingly produce global
      benchmarks that measure national performance across a range of issue areas. This
      article illustrates how international organization benchmarking is a significant
      source of indirect power in world politics by examining two prominent cases in
      which international organizations seek to shape the world through comparative
      metrics: (1) the World Bank-International Finance Corporation Ease of Doing
      Business ranking; and (2) the Organisation for Economic Co-operation and
      Development FDI Regulatory Restrictiveness Index. We argue that the legitimacy
      attached to these benchmarks because of the expertise of the international
      organizations that produce them is highly problematic for two reasons. First,
      both benchmarks oversimplify the evaluation of relative national performance,
      misrepresenting contested political values drawn from a specific transnational
      paradigm as empirical facts. Second, they entrench an arbitrary division in the
      international arena between 'ideal' and 'pathological' types of national
      performance, which (re)produces social hierarchies among states. We argue that
      the ways in which international organizations use benchmarking to orient how
      political actors understand best practices, advocate policy changes and attribute
      political responsibility thus constitutes 'bad science'. Extending research on
      processes of paradigm maintenance and the influence of international
      organizations as teachers of norms or judges of norm compliance, we show how the
      indirect power that international organizations exercise as evaluators of
      relative national performance through benchmarking can be highly consequential
      for the definition of states' policy priorities.

PMID- 30111981
TI  - First case of sternum replacement with a bioceramic prosthesis after radio
      induced sarcoma.
AB  - Objectives: To date, no "gold standard" technique has been developed for sternum
      replacement in cases of radioinduced sarcoma, which is a rare and aggressive
      disease. Current techniques rely on metallic prostheses, meshes, or bone grafts
      procedures that that are associated with several complications. We therefore
      tried a new solution that might simplify and optimize this surgery. Methods: We
      used a porous alumina ceramic prosthesis (Ceramil: i.ceram, Limoges, France) that
      has several interesting characteristics, such as osseointegration,
      biocompatibility, radiolucency, and high mechanical strength. Results: We report
      the first case of sternal replacement surgery involving the implantation of a
      ceramic prosthesis after radio-induced sternal sarcoma. In 2005, a 54-year-old
      woman was diagnosed with local breast cancer for which she underwent all
      appropriate treatment. Ten years later, she developed radio-induced sarcoma of
      the sternum. A complete sternal replacement was performed on 24 April 2015, with
      no postoperative complications. Imaging by 18F-flurodeoxyglucose positron
      emission tomography-computed tomography performed 26 months after the surgery
      showed no local recurrence. The patient seems to have fully recovered and has
      resumed normal activity. Conclusions: This new technique is promising. For the
      first time, we highlight the feasibility, safety, and efficacy of sternal
      replacement using a porous alumina ceramic prosthesis.

PMID- 30111979
TI  - Targeting the PD-1/PD-L1 axis for the treatment of non-small-cell lung cancer.
AB  - Lung cancer is the leading cause of cancer-specific death among Canadians, with
      non-small-cell lung cancer (nsclc) being the most common histologic variant.
      Despite advances in the understanding of the molecular biology of nsclc, the
      survival rate for this malignancy is still poor. It is now understood that, to
      evade detection and immune clearance, nsclc tumours overexpress the
      immunosuppressive checkpoint protein programmed death ligand 1 (PD-L1).
      Inhibiting the PD-1/PD-L1 axis with monoclonal antibodies has significantly
      changed the treatment landscape in nsclc during the last 5 years. Despite
      evidence of clinical response in some patients, only approximately 20% of
      patients obtain any durable benefit, and many of the patients who do respond
      ultimately relapse with drug-resistant disease. The identification of patients
      who are most likely to benefit from such therapy is therefore important. In the
      present review, we cover the basics of the PD-1/PD-L1 axis and its clinical
      significance in nsclc, biomarkers that are predictive of treatment response,
      relevant clinical trials of PD-1/PD-L1 blockade completed to date, and proposed
      mechanisms of acquired therapeutic resistance.

PMID- 30111984
TI  - Global climate adaptation governance: Why is it not legally binding?
AB  - In the last decade, the United Nations Framework Convention on Climate Change has
      moved from a strong focus on mitigation to increasingly address adaptation.
      Climate change is no longer simply about reducing emissions, but also about
      enabling countries to deal with its impacts. Yet, most studies of the climate
      regime have focused on the evolution of mitigation governance and overlooked the
      increasing number of adaptation-related decisions and initiatives. In this
      article, we identify the body of rules and commitments on adaptation and suggest
      that there are more attempts to govern adaptation than many mitigation-focused
      accounts of the international climate regime would suggest. We then ask: to what
      degree are adaptation rules and commitments legalized in the United Nations
      Framework Convention on Climate Change? We examine the degree of precision and
      obligation of relevant decisions through an extensive analysis of primary United
      Nations Framework Convention on Climate Change documents, secondary literature on
      adaptation initiatives and institutions, interviews with climate change experts
      and negotiators, and participant observation at climate negotiations. Our
      analysis finds that adaptation governance is low in precision and obligation. We
      suggest that this is partly because adaptation is a contested global public good
      and because 'package deals' are made with mitigation commitments. This article
      makes a vital contribution to the global environmental politics literature given
      that adaptation governance is under-studied and poorly understood. It also
      contributes to the legalization literature by highlighting how contested global
      public goods may be governed globally, but with low obligation and precision.

PMID- 30111980
TI  - What characterizes cancer family history collection tools? A critical literature
      review.
AB  - Background: Many tools have been developed for the standardized collection of
      cancer family history (fh). However, it remains unclear which tools have the
      potential to help health professionals overcome traditional barriers to
      collecting such histories. In this review, we describe the characteristics,
      validation process, and performance of existing tools and appraise the extent to
      which those tools can support health professionals in identifying and managing at
      risk individuals. Methods: Studies were identified through searches of the
      medline, embase, and Cochrane central databases from October 2015 to September
      2016. Articles were included if they described a cancer fh collection tool, its
      use, and its validation process. Results: Based on seventy-nine articles
      published between February 1978 and September 2016, 62 tools were identified.
      Most of the tools were paper-based and designed to be self-administered by lay
      individuals. One quarter of the tools could automatically produce pedigrees,
      provide cancer-risk assessment, and deliver evidence-based recommendations. One
      third of the tools were validated against a standard reference for collected fh
      quality and cancer-risk assessment. Only 3 tools were integrated into an
      electronic health records system. Conclusions: In the present review, we found no
      tool with characteristics that might make it an efficient clinical support for
      health care providers in cancer-risk identification and management. Adequately
      validated tools that are connected to electronic health records are needed to
      encourage the systematic identification of individuals at increased risk of
      cancer.

PMID- 30111985
TI  - The effects of radical prostatectomy on gay and bisexual men's sexual functioning
      and behavior: qualitative results from the restore study.
AB  - To advance research on the sexual effects of prostate cancer in sexual
      minorities, we conducted telephone interviews with 19 gay and bisexual men (GBM)
      who had undergone radical prostatectomies. Challenges to sexual functioning
      included anatomical penile changes, loss of ejaculate, climacturia, and erectile
      dysfunction. All sexual behavior with other men, not just insertive anal sex, was
      affected, across all stages of the sexual response cycle. Rather than narrowly
      focusing on erectile functioning, rehabilitation for GBM needs to be
      comprehensive in addressing anatomical changes, sexual behavior comprehensively,
      and functioning across the sexual response cycle. Seven recommendations for
      practitioner education are identified.

PMID- 30111986
TI  - Commentary: Risk Assessment in the Age of Evidence-Based Practice and Policy.
AB  - Risk assessment has come to be recognized as a key component of evidence-based
      practice and policy in psychiatric and correctional agencies. At the same time,
      however, there is significant debate in scientific, policy, and public arenas
      regarding the role of risk assessment instruments in mental health and criminal
      justice decision-making, and questions regarding the level of evidence supporting
      their usefulness. It is in light of these conflicting realities that the current
      commentary considers Williams, Wormith, Bonta and Sitarenios' (2017) re
      examination of the Singh, Grann, and Fazel (2011) meta-analysis and
      recommendations made in "The Use of Meta-Analysis to Compare and Select Offender
      Risk Instruments." Additional limitations in the extant risk assessment research
      are identified and their implications for evidence-based practice and policy are
      discussed.

PMID- 30111987
TI  - Growth Responses and Photosynthetic Indices of Bamboo Plant (Indocalamus
      latifolius) under Heavy Metal Stress.
AB  - Investigating factors involved in the alleviation of the toxic effects of heavy
      metals (HMs) on plants is regarded as one of the important research concerns in
      the environmental field. The southern regions of China are severely impacted by
      human-induced heavy metal (HM) contamination, which poses an impediment to growth
      and productivity of bamboo (Indocalamus latifolius) plants. This necessitates the
      investigation of the effects of HMs on growth and physiological properties of
      bamboo. Therefore, the aim of the study was to evaluate some gas exchange and
      growth parameters in two-year-old bamboo species under HMs stress. A greenhouse
      based experiment was conducted at Nanjing Forestry University, where the bamboo
      plant was treated with three HMs (Cu, Pb, and Zn) at four different
      concentrations (0, 500, 1000, and 2000 mg kg-1). The results illustrated that
      excessive HMs (1000 and 2000 mg kg-1) triggered a decline in a number of
      photosynthetic-related indices including the rate of photosynthesis (MUmol CO2 m
      2 s-1), intercellular CO2 concentration (MUmol CO2 mol-1), conductance to H2O
      (mol H2O m-2 s-1), and net assimilation as well as transpiration. Morphological
      indices were also depressed as a result of the adverse influence of HMs, leading
      to decreased shoot length (10 to 73%) and reduced number of emerged plants (6 to
      57%). Also, the results indicated that Pb had the greatest harmful impact on the
      growth indices.

PMID- 30111988
TI  - Detection of Vertical Root Fractures Using Cone-Beam Computed Tomography in the
      Presence and Absence of Gutta-Percha.
AB  - Background: Vertical root fractures (VRFs) can significantly reduce dental
      prognosis. Cone-beam computed tomography (CBCT) offers better visualization of
      VRF than conventional radiography. However, gutta-percha creates artifacts in
      cone-beam CT (CBCT) images and reduces the diagnosis quality. The purpose of this
      study was to evaluate the accuracy of CBCT in detection of VRF in presence and
      absence of gutta-percha in canals. Materials and Methods: In this cross-sectional
      study, 50 extracted mandibular premolars were selected. After preparing the
      access cavity, canals were instrumented using step-back method, and gutta-percha
      #40 was placed afterwards. The fractures were created using electromechanical
      universal testing machine on 25 teeth. The teeth were randomly placed in dry
      mandibular dental sockets, and the first CBCTs were taken. Then the gutta-percha
      was removed, and the second CBCTs were taken. Results: The results of Kappa
      coefficient between two observers in roots with and without gutta-percha were
      0.644 and 0.830, respectively (p value <= 0.001). The sensitivity and specificity
      of VRF diagnosis in assessing gutta-percha filled canals were 32% and 68% for the
      first observer, respectively (Kappa < 0.000, p value = 1.000), and 40% and 68%
      for the second observer, respectively (Kappa = 0.080, p value = 0.556). The
      sensitivity and specificity of VRF diagnosis in assessing the empty canals
      (without gutta-percha) were 72% and 96% for the first observer, respectively
      (Kappa = 0.680, p value <= 0/001), and 72% and 96% for the second observer,
      respectively (Kappa = 0.680, p value <= 0/001). Conclusion: The intracanal
      filling materials such as gutta-percha reduce the diagnostic ability of vertical
      root fractures. Hence, it is recommended to remove those materials from root
      canals before imaging to improve the diagnostic potential of CBCT.

PMID- 30111990
TI  - 10-Year Cardiovascular Disease Risk Estimation Based on Lipid Profile-Based and
      BMI-Based Framingham Risk Scores across Multiple Sociodemographic
      Characteristics: The Malaysian Cohort Project.
AB  - Cardiovascular disease (CVD) leads to high morbidity and mortality rate
      worldwide. Therefore, it is important to determine the risk of CVD across the
      sociodemographic factors to strategize preventive measures. The current study
      consisted of 53,122 adults between the ages of 35 and 65 years from The Malaysian
      Cohort project during recruitment phase from year 2006 to year 2012.
      Sociodemographic profile and physical activity level were assessed via self
      reported questionnaire, whereas relevant CVD-related biomarkers and biophysical
      variables were measured to determine the Framingham Risk Score (FRS). The main
      outcome was the 10-year risk of CVD via FRS calculated based on lipid profile and
      body mass index (BMI) associated formulae. The BMI-based formula yielded a higher
      estimation of 10-year CVD risk than the lipid profile-based formula in the study
      for both males (median = 13.2% and 12.7%, respectively) and females (median =
      4.3% and 4.2%, respectively). The subgroup with the highest risk for 10-year CVD
      events (based on both FRS formulae) was the Malay males who have lower education
      level and low physical activity level. Future strategies for the reduction of CVD
      risk should focus on screening via BMI-based FRS in this at-risk subpopulation to
      increase the cost-effectiveness of the prevention initiatives.

PMID- 30111992
TI  - Corneal Epithelial Hyperplasia after 5-Fluorouracil Injection.
AB  - Background: 5-Fluorouracil (5-FU) is a pyrimidine analogue which selectively
      inhibits DNA synthesis, RNA synthesis, and VEGF antibodies. 5-FU is widely used
      in ophthalmology for inhibition of postoperative corneal scarring and scleral
      bleb fibrosis. Case Presentation: In this case report, we describe an unusual
      case of a 65-year-old male who presented to the clinic with progressive decrease
      of vision after he underwent a revision of scleral bleb with the administration
      of 0.05 mL 5-FU (2.5 mg) injection and was diagnosed with corneal epithelial
      hyperplasia. The patient had a history of glaucoma managed by deep sclerotomy and
      phacoemulsification with intraocular lens implantation. Conclusion: Our case
      demonstrates an unusual consequence of corneal epithelial hyperplasia developed
      after 5-FU injection.

PMID- 30111991
TI  - Pharmacological Evaluation of Selected Medicinal Plants Used in the Management of
      Oral and Skin Infections in Ebem-Ohafia District, Abia State, Nigeria.
AB  - Oral and skin infections contribute significantly to the global health challenges
      responsible for the current trend of increased morbidity and premature death. The
      purpose of this study was to document medicinal plants used in the management of
      oral and skin infections in Ebem-Ohafia Local Government Area (LGA), Abia State,
      and to characterize the in vitro antioxidant and antibacterial activity. The thin
      layer chromatography (TLC) profiling of ten of the selected folklore medicine was
      carried out using a various solvent system of different polarity index. The
      antioxidant capacity of the plant extracts was evaluated using chemical-based
      methods, and its antibacterial effect was investigated using disc diffusion and
      microdilution methods. Sixty-one plant species belonging to 26 families were
      discovered, and the most frequently cited species are Euphorbiaceae (18.03%),
      Fabaceae (11.47%), and Asteraceae (11.47%). All the plant extracts showed a
      promising free radical scavenging activity and efficient ferric reducing
      antioxidant power in a concentration-dependent manner possibly due to their
      richness in polyphenol with TLC profiling showing maximum three bands of
      phytochemicals. Also, the plant extracts exhibited a mild to weak antibacterial
      activity against our panel of bacterial strains having MIC values ranging from
      256 to > 512 MUg/ mL reflected in their zone of inhibition at 10 MUg/disc. The
      data obtained for Breynia nivosa (BN), Eleusine indica (EI), Cassia alata (CA),
      Chromolaena odorata (CO), and Acalypha hispida (AH) extracts substantiate the
      traditional use of these herbal remedies in the region and open the possibility
      for the development of cheaper and affordable drugs in the treatment of oral and
      skin infections. Further studies are needed to identify active ingredient with
      strong antibacterial and antioxidant capacities along with their molecular
      mechanisms.

PMID- 30111993
TI  - Wireless Stimulus-on-Device Design for Novel P300 Hybrid Brain-Computer Interface
      Applications.
AB  - Improving the independent living ability of people who have suffered spinal cord
      injuries (SCIs) is essential for their quality of life. Brain-computer interfaces
      (BCIs) provide promising solutions for people with high-level SCIs. This paper
      proposes a novel and practical P300-based hybrid stimulus-on-device (SoD) BCI
      architecture for wireless networking applications. Instead of a stimulus-on-panel
      architecture (SoP), the proposed SoD architecture provides an intuitive control
      scheme. However, because P300 recognitions rely on the synchronization between
      stimuli and response potentials, the variation of latency between target stimuli
      and elicited P300 is a concern when applying a P300-based BCI to wireless
      applications. In addition, the subject-dependent variation of elicited P300
      affects the performance of the BCI. Thus, an adaptive model that determines an
      appropriate interval for P300 feature extraction was proposed in this paper.
      Hence, this paper employed the artificial bee colony- (ABC-) based interval type
      2 fuzzy logic system (IT2FLS) to deal with the variation of latency between
      target stimuli and elicited P300 so that the proposed P300-based SoD approach
      would be feasible. Furthermore, the target and nontarget stimuli were identified
      in terms of a support vector machine (SVM) classifier. Experimental results
      showed that, from five subjects, the performance of classification and
      information transfer rate were improved after calibrations (86.00% and 24.2 bits/
      min before calibrations; 90.25% and 27.9 bits/ min after calibrations).

PMID- 30111989
TI  - The Notch Pathway in Breast Cancer Progression.
AB  - Objective: Notch signaling pathway is a vital parameter of the mammalian vascular
      system. In this review, the authors summarize the current knowledge about the
      impact of the Notch signaling pathway in breast cancer progression and the
      therapeutic role of Notch's inhibition. Methods: The available literature in
      MEDLINE, PubMed, and Scopus, regarding the role of the Notch pathway in breast
      cancer progression was searched for related articles from about 1973 to 2017
      including terms such as "Notch," "Breast Cancer," and "Angiogenesis." Results.
      Notch signaling controls the differentiation of breast epithelial cells during
      normal development. Studies confirm that the Notch pathway has a major
      participation in breast cancer progression through overexpression and/or abnormal
      genetic type expression of the notch receptors and ligands that determine
      angiogenesis. The cross-talk of Notch and estrogens, the effect of Notch in
      breast cancer stem cells formation, and the dependable Notch overexpression
      during breast tumorigenesis have been studied enough and undoubtedly linked to
      breast cancer development. The already applied therapeutic inhibition of Notch
      for breast cancer can drastically change the course of the disease. Conclusion:
      Current data prove that Notch pathway has a major participation and multiple
      roles during breast tumor progression. Inhibition of Notch receptors and ligands
      provides innovative therapeutic results and could become the therapy of choice in
      the next few years, even though further research is needed to reach safe
      conclusions.

PMID- 30111994
TI  - A Novel Deep Learning Approach for Recognizing Stereotypical Motor Movements
      within and across Subjects on the Autism Spectrum Disorder.
AB  - Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by
      persistent difficulties including repetitive patterns of behavior known as
      stereotypical motor movements (SMM). So far, several techniques have been
      implemented to track and identify SMMs. In this context, we propose a deep
      learning approach for SMM recognition, namely, convolutional neural networks
      (CNN) in time and frequency-domains. To solve the intrasubject SMM variability,
      we propose a robust CNN model for SMM detection within subjects, whose parameters
      are set according to a proper analysis of SMM signals, thereby outperforming
      state-of-the-art SMM classification works. And, to solve the intersubject
      variability, we propose a global, fast, and light-weight framework for SMM
      detection across subjects which combines a knowledge transfer technique with an
      SVM classifier, therefore resolving the "real-life" medical issue associated with
      the lack of supervised SMMs per testing subject in particular. We further show
      that applying transfer learning across domains instead of transfer learning
      within the same domain also generalizes to the SMM target domain, thus
      alleviating the problem of the lack of supervised SMMs in general.

PMID- 30111995
TI  - Unsupervised Domain Adaptation for Facial Expression Recognition Using Generative
      Adversarial Networks.
AB  - In the facial expression recognition task, a good-performing convolutional neural
      network (CNN) model trained on one dataset (source dataset) usually performs
      poorly on another dataset (target dataset). This is because the feature
      distribution of the same emotion varies in different datasets. To improve the
      cross-dataset accuracy of the CNN model, we introduce an unsupervised domain
      adaptation method, which is especially suitable for unlabelled small target
      dataset. In order to solve the problem of lack of samples from the target
      dataset, we train a generative adversarial network (GAN) on the target dataset
      and use the GAN generated samples to fine-tune the model pretrained on the source
      dataset. In the process of fine-tuning, we give the unlabelled GAN generated
      samples distributed pseudolabels dynamically according to the current prediction
      probabilities. Our method can be easily applied to any existing convolutional
      neural networks (CNN). We demonstrate the effectiveness of our method on four
      facial expression recognition datasets with two CNN structures and obtain
      inspiring results.

PMID- 30111996
TI  - Cutaneous Tuberculosis: Clinicopathologic Arrays and Diagnostic Challenges.
AB  - The clinicopathological manifestations of cutaneous tuberculosis are diverse. The
      precise diagnosis is often overlooked, due to clinical presentations as those of
      cutaneous diseases with different etiology and the relative paucity of the
      pathogens in the lesions. Meanwhile, almost all of the diagnostic methods confer
      lower sensitivity and specificities which augments further diagnostic challenges.
      This article revises the current scenario of the disease's physiopathology and
      underscores clinicopathological challenges, due to multifaceted presentations of
      cutaneous tuberculosis, in the diagnosis.

PMID- 30111997
TI  - An Evaluation of the Genotoxicity and Subchronic Oral Toxicity of Synthetic
      Curcumin.
AB  - A battery of toxicological studies was conducted in accordance with international
      guidelines to investigate the genotoxicity and repeated-dose oral toxicity in
      rats of synthetic curcumin (VEAMIN 99, >99% purity). There was no evidence of
      mutagenicity in a bacterial reverse mutation test, whereas an in vitro mammalian
      chromosomal aberration test was positive for induction of chromosomal aberrations
      which is in line with results reported for natural curcumin. There was no
      evidence of genotoxicity in an in vivo mammalian micronucleus test. Synthetic
      curcumin did not cause mortality or toxic effects in a 90-day repeated-dose oral
      toxicity study at daily doses of 250, 500, or 1000 mg/kg body weight (bw)/day
      (administered by gavage in a split dose). The no observed adverse effect level
      (NOAEL) determined from the 90-day study was 1000 mg/kg bw/day for both male and
      female Wistar rats.

PMID- 30111998
TI  - Genotoxicity of Copper and Nickel Nanoparticles in Somatic Cells of Drosophila
      melanogaster.
AB  - Copper and nickel nanoparticles (Cu-NPs and Ni-NPs, respectively) are used in a
      variety of industrial applications, such as semiconductors, catalysts, sensors,
      and antimicrobial agents. Although studies on its potential genotoxicity already
      exist, few of them report in vivo data. In the present study we have used the
      wing-spot assay in Drosophila melanogaster to determine the genotoxic activity of
      Cu-NPs and Ni-NPs, and these data have been compared with those obtained with
      their microparticle forms (MPs). Additionally, a complete physical
      characterization of NPs using transmission electronic microscopy (TEM), dynamic
      light scattering (DLS), and laser Doppler velocimetry (LDV) techniques was also
      performed. Results obtained with Cu-NPs and Cu-MPs indicate that both failed to
      induce an increase in the frequency of mutant spots formation in the wings of the
      adults, suggesting a lack of genotoxicity in somatic cells of D. melanogaster.
      However, when Ni-NPs and Ni-MPs were evaluated, a significant increase of small
      single spots and total mutant spots was observed only for Ni-NPs (P<0.05) at the
      highest dose assessed. Thus, the genotoxicity of Ni-NPs seem to be related to
      their nanoscale size, because no genotoxic effects have been reported with their
      microparticles and ions. This study is the first assessing the in vivo genotoxic
      potential of Cu-NPs and Ni-NPs in the Drosophila model.

PMID- 30111999
TI  - S100A4 May Be a Good Prognostic Marker and a Therapeutic Target for Colon Cancer.
AB  - Background: Globally, the colorectal cancers rank the third in terms of cancer
      incidence and rank the fourth in cancer-associated deaths. S100A4, an important
      member of the S100 protein family, serves to promote tumor progression and
      metastasis. By conducting this study, we aim to examine the role of S100A4 in the
      prognosis of colon cancer and to demonstrate its prognostic significance.
      Methods: Tissue samples of colon cancer from 148 patients who underwent colon
      resection due to colon cancer were analyzed by immunohistochemical staining to
      determine the protein expression levels of S100A4. The protein expression levels
      of S100A4 in tumor tissue were matched with the clinicopathologic factors
      including patient survival. Results: Cytoplasmic expression of S100A4 protein was
      demonstrated in the tumor tissue of 132 patients (89.2%) out of a total of 148
      study patients. Statistically, the expression levels of the cytoplasmic S100A4
      protein correlated significantly with the TNM stages and patient survival. The
      distribution of the S100A4 protein staining in the tumor tissue was associated
      with the age groups, tumor localization, TNM staging, and patient survival with
      statistical significance. The levels of S100A4 protein expression were found to
      be an independent prognostic factor for TNM staging and poor survival.
      Conclusion: Expression of the S100A4 protein in colon cancers may be an indicator
      of tumor progression and lymph node metastasis and may be useful for predicting
      the overall survival of the patients with colon cancer. In patients with colon
      cancer, it may be used as an indicator of poor prognosis.

PMID- 30112001
TI  - Clinical and Molecular Characteristics Associated with Survival in Advanced
      Melanoma Treated with Checkpoint Inhibitors.
AB  - Background: We performed meta-analysis to gather more evidence regarding clinical
      molecular subgroups associated with better overall survival (OS) in advanced
      melanoma treated with checkpoint inhibitors. Materials and Methods: We performed
      a systematic search of PubMed, Scopus, Cochrane Library, and clinical trial.gov.
      Randomized clinical trials that compared a checkpoint inhibitor (nivolumab or
      pembrolizumab) with investigator choice chemotherapy or ipilimumab were included
      in our study. Hazard ratios (HR) and confidence interval (CI) were calculated for
      progression-free survival (PFS) and OS for each subgroup using generic inverse
      model along with the random effect method. Results: A total of 6 clinical trials
      were eligible for the meta-analysis. OS was prolonged in wild BRAF subgroup (HR
      0.65, 95% CI 0.49-0.85, p 0.002), Programmed cell death subgroup (PD-1+) (HR
      0.57, 95% CI 0.41-0.80, p 0.001), and high lactate dehydrogenase (LDH) level
      subgroup (HR 0.60, 95% CI 0.38-0.95, p 0.03). Similarly, we found increased OS in
      eastern cooperative oncology group (ECOG) 1, males and age >65 years subgroups.
      Conclusions: Checkpoint inhibitors significantly increased OS in patients with
      wild BRAF, positive PD-1, and high LDH. However, results should be interpreted
      keeping in mind associated significant heterogeneity. The results of this study
      should help in designing future clinical trials.

PMID- 30112002
TI  - Host-Guest Extraction of Heavy Metal Ions with p-t-Butylcalix[8]arene from
      Ammonia or Amine Solutions.
AB  - The capacities of the p-t-butylcalix[8]arene (abbreviated as H8L) host to extract
      toxic divalent heavy metal ions and silver from aqueous solution phases
      containing ammonia or ethylene diamine to an organic phase (nitrobenzene,
      dichloromethane, or chloroform) were carried out. When the metal ions were
      extracted from an aqueous ammonia solution, the metal ion selectivity for
      extraction was found to decrease in the order Cd2+> Ni2+> Cu2+> Ag+> Co2+> Zn2+.
      When the aqueous phase contained ethylene diamine, excellent extraction
      efficiencies of 97% and 90% were observed for the heavy metal ions Cu2+ and Cd2+,
      respectively. Under the same conditions the extraction of octahedral type metal
      ions, namely, Co2+ and Ni2+, was suppressed. The extraction of transition metal
      cations by H8L in ammonia and/or amine was found to be pH dependent. Detailed
      analysis of extraction behavior was investigated by slope analysis, the
      continuous variation method, and by loading tests.

PMID- 30112000
TI  - Inhibition of MDM2 via Nutlin-3A: A Potential Therapeutic Approach for Pleural
      Mesotheliomas with MDM2-Induced Inactivation of Wild-Type P53.
AB  - Previously, our group demonstrated that nuclear expression of E3 ubiquitin ligase
      (MDM2) in malignant pleural mesothelioma (MPM) is significantly associated with
      decreased overall survival. A possible explanation may be that overexpression of
      MDM2 leads to a proteasomal degradation of TP53 that eventually results in a loss
      of TP53-induced apoptosis and senescence. It is well known from other tumor
      entities that restoration of TP53 activity, e.g., by MDM2 inhibition, results in
      an instant TP53-induced stress and/or DNA damage response of cancer cells. Nutlin
      3A (a cis-imidazoline analogue) has been described as a potent and selective MDM2
      inhibitor preventing MDM2-TP53-interaction by specific binding to the hydrophobic
      TP53-binding pocket of MDM2. In the present study, the effects of MDM2 inhibition
      in MPM via Nutlin-3A and standard platinum based chemotherapeutic agents were
      comparatively tested in three MPM cell lines (NCI-H2052, MSTO-211H, and NCI
      H2452) showing different expression profiles of TP53, MDM2, and its physiological
      inhibitor of MDM2-P14/ARF. Our in vitro experiments on MPM cell lines revealed
      that Nutlin-3A in combination with cisplatin resulted in up to 9.75 times higher
      induction of senescence (p=0.0050) and up to 5 times higher apoptosis rate
      (p=0.0067) compared to the commonly applied cisplatin and pemetrexed regimens.
      Thus Nutlin-3A, a potent inhibitor of MDM2, is associated with a significant
      induction of senescence and apoptosis in MPM cell lines, making Nutlin-3A a
      promising substance for a targeted therapy in the subgroup of MPM showing MDM2
      overexpression.

PMID- 30112003
TI  - Two-Dimensional Thin Layer Chromatography-Bioautography Designed to Separate and
      Locate Metabolites with Antioxidant Activity Contained on Spirulina platensis.
AB  - Spirulina platensis contains several biologically active compounds, some of them
      with antioxidant activity. Nevertheless, not all of these compounds have been
      identified to date. As a first step to achieving such identification, a
      methodology to perform two-dimensional thin layer chromatography bioautographies
      on silica gel thin layer chromatography plates was proposed. Starting with a
      reference binary system, 5 other binary systems were tested, in which the
      relative polarity was systematically increased. To further improve the separation
      behavior, a phase modifier (NH4OH) was used. The best separation results were
      obtained with the isopropyl alcohol/ethyl acetate/NH4OH ternary system. This
      experimental system allowed four well-resolved spots showing antioxidant activity
      as well as two additional areas with mixtures containing antioxidant compounds.
      Although the proposed methodology was designed with a specific application, it
      would be predictable that its field of use could be considerably greater, making
      the convenient modifications on the solvent polarity and "masking level" produced
      by the ammonium derivatives.

PMID- 30112004
TI  - Quantitative Determination of Chlormequat Chloride Residue in Wheat Using Surface
      Enhanced Raman Spectroscopy.
AB  - A simple and sensitive method for detection of chlormequat chloride residue in
      wheat was developed using surface-enhanced Raman spectroscopy (SERS) coupled with
      chemometric methods on a portable Raman spectrometer. Pretreatment of wheat
      samples was performed using a two-step extraction procedure. Effective and
      uniform active substrate (gold nanorods) was prepared and mixed with the sample
      extraction solution for SERS measurement. The limit of detection for chlormequat
      chloride in wheat extracting solutions and wheat samples was 0.25 mg/L and 0.25
      MUg/g, which was far below the maximum residual value in wheat of China. Then,
      support vector regression (SVR) and kernel principal component analysis (KPCA),
      multiple linear regression, and partial least squares regression were employed to
      develop the regression models for quantitative analysis of chlormequat chloride
      residue with spectra around the characteristic peaks at 666, 713, and 853 cm-1.
      As for the residue in wheat, the predicted recovery of established optimal model
      was in the range of 94.7% to 104.6%, and the standard deviation was about 0.007
      mg/L to 0.066 mg/L. The results demonstrated that SERS, SVR, and KPCA can provide
      the accurate and quantitative determination for chlormequat chloride residue in
      wheat.

PMID- 30112005
TI  - Gum Arabic Fibers Decreased Inflammatory Markers and Disease Severity Score among
      Rheumatoid Arthritis Patients, Phase II Trial.
AB  - Background: Rheumatoid arthritis (RA) is autoimmune inflammatory disease that
      attacks the synovium of the joints. Both TNFa and interleukin-1 play crucial
      roles in the pathogenesis of RA. Gum Arabic (GA) is gummy exudates from Acacia
      senegal tree. Gum Arabic fermentation by colonic bacteria increases serum
      butyrate concentrations, so it is considered as prebiotic agent. Gum Arabic (GA)
      has anti-inflammatory activity through its derivative butyrate. To the best of
      our knowledge, this is the first study conducted to investigate GA intake on
      inflammatory markers among RA patients. Patients and Methods: This is clinical
      trial phase II in which 40 patients were enrolled aged 18 to 70 years. Patients
      received 30g/day GA for 12 weeks. TNF alpha, ESR, and complete blood count were
      measured and DAS-28 was calculated before and after regular GA consumption. Study
      was approved by the Ethical committee of National Medicines and Poisons Board.
      Results: This study showed significant decrease in level of serum TNF alpha (p
      value 0.05) [95% CI, 0.65 -16.5], ESR (p value 0.011) [95% CI, 2.6 -18.89], and
      number of swollen and tender joints in RA patients after 12 weeks of GA intake
      which reflected as significant decrease in disease severity score DAS 28 P.V:0.00
      [95% CI, 1.25 -1.99]. On the other hand, GA had trivial change in blood indices.
      Conclusion: Gum Arabic has favorable immune modulator effect on rheumatoid
      arthritis. It can be utilized in clinical practice as adjuvant therapy. Trial
      Registration: This trial was registered with ClinicalTrials.gov Identifier:
      NCT02804581 Registered at 19 June 2016, prospective registration.

PMID- 30112006
TI  - Wrist Arthrodesis in Rheumatoid Arthritis Using an LCP Metaphyseal Locking Plate
      versus an AO Wrist Fusion Plate.
AB  - Objectives: Although wrist arthrodesis using a plate is an established treatment
      with a well-documented successful union rate for severely destroyed wrists, plate
      related complications are a matter of great concern. Methods: We retrospectively
      compared wrist arthrodesis using an AO wrist fusion plate in nine and a locking
      compression plate (LCP) metaphyseal plate in seven cases of rheumatoid arthritis.
      Results: The mean follow-up was 40.6 months in the AO wrist fusion plate group
      and 57.2 months in the LCP metaphyseal plate group. Bone union at the arthrodesis
      site was achieved in all cases in both groups. Comparison of the original
      position of the fusion on the immediate postoperative radiographs and the
      position on the most recent follow-up radiographs demonstrated good stability in
      both groups. Plate-related complications occurred in four cases in the AO wrist
      fusion plate group and no cases in the LCP metaphyseal plate group. Complications
      included pain over the plate, wound dehiscence and infection, extensor tendon
      adhesion, and fracture in one case each. Conclusion: Wrist arthrodesis using an
      LCP metaphyseal plate was favorable for rheumatoid arthritis patients with
      comparable stability to that of and a lower risk of plate-related complications
      than an AO wrist fusion plate.

PMID- 30112007
TI  - Asymptomatic Plasmodium Parasites among Adults in Eastern Uganda: A Case of Donor
      Blood Screening at Mbale Regional Blood Bank.
AB  - Background: There is a paucity of data on asymptomatic carriage of Plasmodium
      parasite among adult population in Eastern Uganda, an area of perennial high
      transmission of malaria. In this study, we estimated the prevalence of Plasmodium
      parasites in donor blood units at Mbale Regional Blood Bank (Mbale RBB), a
      satellite centre of the Uganda Blood Transfusion Service (UBTS). Method: This was
      a cross-sectional descriptive study in which 380 screened donor blood units were
      examined for the presence of Plasmodium parasites. A systematic random sampling
      technique using the interval of 7 was used in selecting the screened blood units
      for testing. Two experienced malaria slide microscopists (MC1 and MC2)
      independently examined each thick and thin blood slide under high power
      magnification of X400 and then X1000 as stated on the study standard operation
      procedure (SOP). Each slide was examined for 100 oil immersion fields before the
      examiner declared them negative for Plasmodium parasites. The results by each
      microscopist's examination were tallied separately, and finally, the two tallies
      were compared. The third independent microscopist (MC3) was blinded to the
      results from MC1 and MC2, but whose role was to perform quality control on the
      slides randomly sampled and read 38 (10%) of all the slides and was available to
      examine any slides with inconsistent findings by MC1 or MC2. Results: All the
      microscopists were unanimous in all the slide readings. Five of the thick smears
      (1.3%) confirmed the presence of Plasmodium parasites among donor blood units. Of
      these, 4/5 were from male donors. Plasmodium falciparum was identified in 4
      positive samples, while Plasmodium malariae was identified in one of the donor
      units. Conclusion: The 1.3% prevalence of Plasmodium malaria parasites in
      screened donor blood units represents risk of malaria blood transfusion
      transmitted infection and a pool of community transmittable malaria infections,
      respectively.

PMID- 30112008
TI  - Amoebic Liver Abscess and Indigenous Alcoholic Beverages in the Tropics.
AB  - Amoebic liver abscess (ALA) seen commonly in the tropics is predominantly
      confined to adult males, especially those who consume locally brewed alcohol,
      although intestinal amoebiasis occurs in all age groups and in both genders.
      Whether the role of alcohol in the development of ALA is incidental and casual or
      whether alcohol is causally implicated has been debated. It has been argued that
      socioeconomic factors and poor sanitary conditions are the primary culprits that
      casually link alcohol to ALA. However, there has emerged an abundance of data
      that implicates alcohol in a more causal role in facilitating the extraintestinal
      invasion of the infective protozoan and the subsequent development of ALA. These
      factors include the role of alcohol in host immunity, parasitic proliferation,
      and invasion and in creating a conducive hepatic microenvironment. The
      contributory role of alcohol-induced increase in hepatic iron stores and lipid
      content is discussed. Late-stage liver disease with fibrosis seems to be
      protective for the development of ALA. Further research is necessary to elucidate
      the many possible mechanisms that predispose to hepatic amoebiasis, so that
      appropriate individual and population-based preventive measures can be
      implemented.

PMID- 30112009
TI  - The Threat of Ambient Air Pollution in Kathmandu, Nepal.
AB  - Air pollution has been a major problem of 21st century for both developed and
      developing world. It has a negative impact on various environmental aspects which
      directly or indirectly affect the quality of human health. Nepal, especially
      Kathmandu, in the current situation, is observing rapid urbanization and various
      infrastructure development projects. As a result, these sorts of human activities
      have been responsible for increasing air pollution in an enormous rate inside
      Kathmandu Valley. Chronic exposure of deteriorated air increases the chance of
      Noncommunicable Disease (NCD) like lung disease, heart disease, and cancers.
      Short term exposures also invite respiratory diseases and allergy. This review is
      an attempt to summarize the updated knowledge on the threat of air pollution on
      public health and discuss the sources of air pollutants in Kathmandu. We reviewed
      the literatures that were published in PMC, MEDLINE, life science journals, and
      organization official websites and finally came up with the findings and their
      interpretation that reveal the current scenario in the context of Kathmandu's air
      quality status and its impact on human health. The knowledge about the invisible
      killer's role in causing acute and chronic diseases may help in finding out the
      answer of the question regarding its effect and prevention.

PMID- 30112010
TI  - Microbiological Quality and Contamination Level of Water Sources in Isiolo County
      in Kenya.
AB  - Water security and safety is of vital concern in arid and semiarid regions of
      Kenya. Potable water accessibility and supply is limited due to fluctuating
      climatic conditions and environmental pollution that lower the wholesomeness of
      most water sources. The aim of this study was to establish the suitability of
      these water sources for drinking and use in industrial food processing by the
      small and medium enterprises (SME's). The aim of this study was to establish
      suitability of these water sources for drinking and use in industrial food
      processing by the small and medium enterprises (SME's). A total of 60 surface and
      ground water sources samples were purposively collected aseptically from the four
      administrative units (Ngare Mara, LMD, Leparua, and Wabera) of Isiolo County. ISO
      16649-3, 688-2, 7937, 9308-1, and 18744 were used for enumeration of E.coli,
      Staphylococcus aureus, Clostridium pafringens, Coliforms, and cysts. Highest mean
      Clostridium pafringens counts in ground and surface water were 1452 Cfu/ml and
      3421 Cfu/ml, respectively. Mean Staphylococcus aureus counts were 740 Cfu/ml and
      1333 Cfu/ml in surface water and ground water, respectively. Escherichia coli and
      Coliforms contamination accounted for 29.88 % and 88.2 %, respectively. Microbial
      counts in the water sources differed significantly (p<=0.05). Total coliforms had
      a significant negative relationship (r = -0.76) with residual chlorine. Ground
      and surface water sources were highly contaminated with microorganism to levels
      regarded as unsafe by the Kenyan and WHO standards for potable water. Point-of
      use water disinfection is thus necessary.

PMID- 30112012
TI  - Adverse Childhood Experiences, Health-Related Quality of Life, and Chronic
      Disease Risks in Rural Areas of the United States.
AB  - Exposure to adverse childhood experiences (ACEs) is associated with increased
      odds of high-risk behaviors and adverse health outcomes. This study examined
      whether ACE exposure among individuals living in rural areas of the United States
      is associated with adult activity limitations, self-reported general poor health
      status, chronic diseases, and poor mental health. Data from the 2011 and 2012
      Behavioral Risk Factor Surveillance System (BRFSS) (N=79,810) from nine states
      were used to calculate the prevalence of ACEs in rural and urban areas. ACE
      scores were determined by summing 11 survey items. Multiple logistic regression
      was used to examine the association between ACE scores and health outcomes,
      including self-reported general health status, chronic diseases, and health
      related quality of life. Approximately 55.4% of rural respondents aged >=18 years
      reported at least one ACE and 14.7% reported experiencing >=4 ACEs in their
      childhood, compared to 59.5% of urban residents who reported at least one ACE and
      15.5% reporting >=4 ACEs. After adjusting for sociodemographic covariates,
      compared to rural respondents who never reported an ACE, rural respondents who
      experienced >=1 ACEs had increased odds of reporting fair/poor general health,
      activity limitations, and heart disease, which is consistent with previous
      studies. The odds of experiencing a heart attack were higher for rural residents
      reporting 2 and >=4 ACEs; the odds of diabetes were higher for those with 3 ACEs;
      and the odds of ever having asthma or poor mental health was higher for those
      with >=3 ACEs. Although individuals in rural areas are less likely to experience
      ACEs, over half of rural respondents reported experiencing an ACE in childhood.
      Programs aimed at preventing ACEs, including child maltreatment, can benefit
      rural areas by reducing adult morbidity and increasing quality of life.

PMID- 30112013
TI  - Anti-cartel thrillers as a new film genre: How regulator-produced films portray
      and problematize cartels and communicate deterrence.
AB  - This article directs the 'visual turn' in criminology to corporate crime, a topic
      that has been understudied by cultural criminologists. A recent trend of
      corporate crime movies suggests that film can compellingly critique economic
      crime and unethical business cultures. This article studies how law enforcement
      agencies, particularly competition authorities, have connected with this trend by
      using film in their communicative strategy. This article introduces the emerging
      genre of anti-cartel enforcement thrillers: regulator-produced realistic
      docudramas in which fictional cartels are exposed and punished. These films'
      narratives about cartel enforcement are reconstructed by studying how the films
      portray cartels, perpetrators and their motives, and the regulator. An analysis
      of four films produced in four jurisdictions demonstrates that the films deter
      only to the extent that the local legal and political-economic context allows:
      the British film reflects that country's neoliberal 'pro-business' climate, while
      the Swedish film depicts businesses as socially responsible and the Dutch film is
      pragmatic rather than moralistic. Only the Australian film is explicitly punitive
      in its narrative as well as its imaginary, and exemplifies the persuasive
      potential of film in enforcement.

PMID- 30112014
TI  - Pleural effusion in a 7-year-old child - with unique cells.

PMID- 30112016
TI  - Cytodiagnosis of extramedullary hematopoiesis in serous effusion: A rare
      presentation unfolding the underlying etiology.
AB  - Extramedullary hematopoiesis (EMH) usually involves reticuloendothelial system.
      However, it rarely may be present in the serous body effusions. In our case, the
      fluid cytology of both peritoneal and pleural fluid was diagnostic of the EMH in
      a patient with an undiagnosed underlying etiology.

PMID- 30112015
TI  - Adult exogenous lipoid pneumonia: A rare and underrecognized entity in cytology -
      A case series.
AB  - Background: Exogenous lipoid pneumonia (ELP) is a rare benign entity without
      specific clinical or imaging presentation. Although cytological studies - either
      bronchoalveolar lavage (BAL) or fine-needle aspiration (FNA) - may be pursued in
      patients with ELP, a definitive diagnosis is frequently rendered only on
      histology. The aim of this study is to highlight the cytological features of ELP.
      Methods: A search of cytopathology (CP) and surgical pathology (SP) diagnoses of
      ELP was conducted. The corresponding clinical and imaging features were obtained,
      and the morphology, particularly the presence and size of the intracytoplasmic
      vacuoles and background, was assessed. Results: Nine cases of ELP were
      identified, including eight with corresponding CP and SP. A neoplasm was
      suspected in three based on imaging, but ELP was not in the differential
      clinically or radiographically in any. Among the cases, six patients had BALs and
      three FNAs. All of the samples showed multiple large vacuoles within macrophages
      with at least some equal to or larger than the size of the cell nucleus. Similar
      vacuoles were noted extracellularly on smears. Conclusions: ELP is typically
      described in case reports in the clinical or radiological literature. To the best
      of our knowledge, this represents the largest series of adult ELP in CP. When
      large vacuoles are present in macrophages in cytology specimens, at least a
      suspicion of ELP can be suggested to initiate appropriate therapy,
      identify/remove the inciting agent, and preclude a more invasive procedure.

PMID- 30112017
TI  - Clustered Breeding Sites: Shelters for Vector-Borne Diseases.
AB  - Here, the propagation of vector-borne diseases is modeled by using a
      probabilistic cellular automaton. Numerical simulations considering distinct
      spatial distributions and time variations of the vector abundance are performed,
      in order to investigate their impacts on the number of infected individuals of
      the host population. The main conclusion is as follows: in the clustered
      distributions, the prevalence is lower, but the eradication is more difficult to
      be achieved, as compared to homogeneous distributions. This result can be
      relevant in the implementation of preventive surveillance measures.

PMID- 30112011
TI  - The Effect of Tobacco Smoking on Musculoskeletal Health: A Systematic Review.
AB  - This systematic review explored associations between smoking and health outcomes
      involving the musculoskeletal system. AMSTAR criteria were followed. A
      comprehensive search of PubMed, Web of Science, and Science Direct returned 243
      articles meeting inclusion criteria. A majority of studies found smoking has
      negative effects on the musculoskeletal system. In research on bones, smoking was
      associated with lower BMD, increased fracture risk, periodontitis, alveolar bone
      loss, and dental implant failure. In research on joints, smoking was associated
      with increased joint disease activity, poor functional outcomes, and poor
      therapeutic response. There was also evidence of adverse effects on muscles,
      tendons, cartilage, and ligaments. There were few studies on the musculoskeletal
      health outcomes of secondhand smoke, smoking cessation, or other modes of
      smoking, such as waterpipes or electronic cigarettes. This review found evidence
      that suggests tobacco smoking has negative effects on the health outcomes of the
      musculoskeletal system. There is a need for further research to understand
      mechanisms of action for the effects of smoking on the musculoskeletal system and
      to increase awareness of healthcare providers and community members of the
      adverse effects of smoking on the musculoskeletal system.

PMID- 30112018
TI  - Analysis and Study of Diabetes Follow-Up Data Using a Data-Mining-Based Approach
      in New Urban Area of Urumqi, Xinjiang, China, 2016-2017.
AB  - The focus of this study is the use of machine learning methods that combine
      feature selection and imbalanced process (SMOTE algorithm) to classify and
      predict diabetes follow-up control satisfaction data. After the feature selection
      and unbalanced process, diabetes follow-up data of the New Urban Area of Urumqi,
      Xinjiang, was used as input variables of support vector machine (SVM), decision
      tree, and integrated learning model (Adaboost and Bagging) for modeling and
      prediction. The experimental results show that Adaboost algorithm produces better
      classification results. For the test set, the G-mean was 94.65%, the area under
      the ROC curve (AUC) was 0.9817, and the important variables in the classification
      process, fasting blood glucose, age, and BMI were given. The performance of the
      decision tree model in the test set is relatively lower than that of the support
      vector machine and the ensemble learning model. The prediction results of these
      classification models are sufficient. Compared with a single classifier, ensemble
      learning algorithms show different degrees of increase in classification
      accuracy. The Adaboost algorithm can be used for the prediction of diabetes
      follow-up and control satisfaction data.

PMID- 30112020
TI  - MicroRNA-153 functions as a tumor suppressor in gastric cancer via targeting
      Kruppel-like factor 5.
AB  - Various microRNAs (miRs) have been demonstrated to serve important roles in
      gastric cancer (GC). miR-153 in particular has been reported to serve a
      suppressive role in GC; however, the underlying mechanism remains unclear. In the
      present study Reverse transcription-quantitative polymerase chain reaction and
      western blot analysis were used to examine the mRNA and protein expression of
      Kruppel-like factor 5. An MTT, wound healing and transwell assay were used to
      study cell proliferation, migration and invasion, respectively. In the present
      study, quantitative polymerase chain reaction data indicated that miR-153 was
      significantly downregulated in GC tissues compared with the adjacent non-tumor
      tissues. In addition, the reduced expression of miR-153 was significantly
      associated with GC aggressiveness and poor prognosis of patients. The expression
      of miR-153 was also reduced in GC cell lines, including KATO III, NCI-N87, SNU-16
      and SNU-5, when compared with normal gastric epithelial GES-1 cells.
      Overexpression of miR-153 in the GC SNU-5 cells by miR-153 mimic transfection
      significantly inhibited the cell proliferation, migration and invasion.
      Furthermore, KLF5 was identified as a target gene of miR-153 in SNU-5 cells by
      bioinformatics prediction. It was observed that KLF5 was significantly
      upregulated in GC tissues and cell lines, and its expression was negatively
      regulated by miR-153 in SNU-5 cells. Overexpression of KLF5 impaired the
      suppressive effects of miR-153 on the proliferation, migration and invasion of
      SNU-5 cells. In conclusion, the present study demonstrated that miR-153 serves a
      tumor suppressive role in GC, at least partly, through directly targeting KLF5,
      thus highlighting the clinical significance of miR-153 in GC.

PMID- 30112019
TI  - Combined diagnosis of breast cancer in the early stage by MRI and detection of
      gene expression.
AB  - Breast cancer is one of the most common cancer types in humans. Magnetic
      resonance imaging (MRI) is an efficient method for the detection of human breast
      cancer. However, the efficacy of MRI in detecting breast cancer in the early
      stage requires to be improved. The present study investigated the diagnostic
      efficacy of a combination of MRI and detection of gene expression in patients
      with breast cancer in the early stage. The gene expression levels of Ki-67,
      BCL11A, FOXC1, HOXD13, PCDHGB7 and her-2 were used as an auxiliary diagnostic
      index for patients with breast cancer in the early stage. Higher expression
      levels of TPA and C2erbB22 were observed in tumor tissue obtained from diagnostic
      biopsy and determined by immunohistochemistry, which indicated a higher risk of
      breast cancer in a total of 84 participants. Diagnostic data revealed that
      combination MRI and detection of gene expression had a significantly higher
      diagnostic rate (66/84) in diagnosing breast cancer in an early stage compared
      with either MRI (78/360) or detection of gene expression (72/84; P<0.01). It was
      indicated that the combination of MRI and detection of gene expression had a
      higher diagnostic rate (94.5%) than either MRI (81.4%) or detection of gene
      expression (75.5%). Histological analysis confirmed the diagnosis determined by
      MRI and detection of gene expression. These results suggest that the combination
      of MRI and detection of gene expression may be a potential diagnostic method for
      assessing patients with early-stage breast cancer.

PMID- 30112021
TI  - Revisiting Connectivity Map from a gene co-expression network analysis.
AB  - The Connectivity Map (CMap) is a tool that has been extensively utilized to study
      drug repositioning and side-effect prediction. However, most of these analyses
      rely on signature genes, ignoring the pathways by which those genes are
      regulated, as well as the functional overlap of redundant genes. The present
      study utilized a systems biology approach referred to as Weighted Gene Co
      expression Network Analysis (WGCNA) to dissect the transcriptional profiles of
      CMap and reveal these hidden factors. Seven common modules associated with
      protein binding, extracellular matrix organization and translation were
      identified. Furthermore, drugs were clustered based on module expression to infer
      their mechanism of action (MoA) based on common activity profiles. As an
      extension of this, an example of disease-based module projection to identify
      novel drugs was provided. The analysis developed in the present study may provide
      a novel framework for drug repositioning or discovering MoAs.

PMID- 30112022
TI  - Anti-HBV effect of interferon-thymosin alpha1 recombinant proteins in transgenic
      Dunaliella salina in vitro and in vivo.
AB  - The aim of the present study was to investigate the anti-hepatitis B virus (HBV)
      effect of interferon (IFN)-thymosin alpha1 (TA1) in a transgenic Dunaliella
      salina (TDS) system in vitro and in vivo. The toxicity of TDS in the HepG2.2.15
      cell line was assessed using an MTT assay. The effect of TDS on the secretion of
      HBV early antigen (HBeAg) and HBV surface antigen (HBsAg) in culture supernatants
      was measured using ELISA. In addition, HBV-DNA was analyzed using quantitative
      polymerase chain reaction. Drug treatment experiments were performed in vivo on
      ducks congenitally infected with duck HBV (DHBV). The drug was administered once
      daily for 21 continuous days. Blood was drawn from all ducks prior to treatment,
      following treatment for 7, 14 and 21 days, and following drug withdrawal for 5
      days. Serum DHBV-DNA was determined using quantitative PCR. In addition, the
      histology of duck liver tissues was assessed using hematoxylin and eosin, and
      orcein staining. The results demonstrated that TDS suppressed cell viability and
      HBsAg and HBeAg secretion in HepG2.2.15 cells. Furthermore, the treatment index
      values for HBsAg and HBeAg following TDS treatment were 2.96 and 3.07
      respectively, which were greater than those of the IFN-alpha treated group. In
      addition, the DHBV-infected duck model experiments indicated that serum DHBV-DNA
      levels were significantly decreased in the group of TDS (20 g/kg) following
      treatment for 7, 14 and 21 days compared with the control group. Following
      withdrawal of the drug for 5 days, the levels of DHBV-DNA did not relapse in the
      medium and high dose groups of TDS (10 and 20 g/kg, respectively). Histological
      analysis of duck liver also demonstrated that TDS and IFN-alpha treatment
      alleviated inflammation and HBsAg signals in duck livers. In conclusion, TDS
      markedly suppresses HBV replication in vitro and in vivo and its anti-HBV effect
      is greater than that of IFN-alpha.

PMID- 30112023
TI  - In vitro screening of cytotoxic activity of euphol from Euphorbia tirucalli on a
      large panel of human cancer-derived cell lines.
AB  - A large number of classic antineoplastic agents are derived from plants.
      Euphorbia tirucalli L. (Euphorbiaceae) is a subtropical and tropical plant, used
      in Brazilian folk medicine against many diseases, including cancer, yet little is
      known about its true anticancer properties. The present study evaluated the
      antitumor effect of the tetracyclic triterpene alcohol, euphol, the main
      constituent of E. tirucalli in a panel of 73 human cancer lines from 15 tumor
      types. The biological effect of euphol in pancreatic cells was also assessed. The
      combination index was further used to explore euphol interactions with standard
      drugs. Euphol showed a cytotoxicity effect against several cancer cell lines
      (IC50 range, 1.41-38.89 uM), particularly in esophageal squamous cell (11.08 uM)
      and pancreatic carcinoma cells (6.84 uM), followed by prostate, melanoma, and
      colon cancer. Cytotoxicity effects were seen in all cancer cell lines, with more
      than half deemed highly sensitive. Euphol inhibited proliferation, motility and
      colony formation in pancreatic cancer cells. Importantly, euphol exhibited
      synergistic interactions with gemcitabine and paclitaxel in pancreatic and
      esophageal cell lines, respectively. To the best of our knowledge, this study
      constitutes the largest in vitro screening of euphol efficacy on cancer cell
      lines and revealed its in vitro anti-cancer properties, particularly in
      pancreatic and esophageal cell lines, suggesting that euphol, either as a single
      agent or in combination with conventional chemotherapy, is a potential anti
      cancer drug.

PMID- 30112024
TI  - Expression of Keap1 and Nrf2 in diffuse large B-cell lymphoma and its clinical
      significance.
AB  - The present study investigated the expression and clinical significance of kelch
      like ECH-associated protein 1 (Keap1) and nuclear factor erythroid-2-related
      factor-2 (Nrf2) expression in diffuse large B-cell lymphoma (DLBCL). These
      proteins were detected by immunohistochemistry in 39 DLBCL cases and 17 cases of
      reactive lymph node hyperplasia, and their association with the
      clinicopathological features of DLBCL patients was analyzed. In DLBCL, the
      percentage of cells with positive staining for Keap1 and Nrf2 was 46.2 and 35.9%,
      respectively, which was significantly higher than that in reactive lymph node
      hyperplasia (17.7 and 5.9%, respectively). There was no correlation between Keap1
      and Nrf2 expression according to a Spearman rank correlation analysis (r=0.272;
      P>0.05). Keap1 and Nrf2 expression was associated with the international
      prognostic index and Ann-Arbor clinical stage (P<0.05), and Keap1 and Nrf2
      expression was higher in DLBCL patients with stage III-IV (68.4 and 52.6%,
      respectively) compared with in those with stage I-II (25.0 and 20.0%,
      respectively). The aberrant expression of Keap1 and Nrf2 in DLBCL suggests that
      these factors may have crucial roles in the development and progression of the
      disease, and may therefore be used as prognostic indicators.

PMID- 30112025
TI  - Evaluation of blood vessel injury, oxidative stress and circulating inflammatory
      factors in an L-NAME-induced preeclampsia-like rat model.
AB  - Preeclampsia is a pregnancy-specific disease characterized by hypertension as
      well as proteinuria after the 20th week of pregnancy. Animal models are effective
      tools for studying the pathogenesis, diagnostic criteria and treatment methods of
      preeclampsia. The present study sought to establish and evaluate a preeclampsia
      like Sprague Dawley (SD) rat model using N-nitro-L-arginine methyl ester (L
      NAME). Rats were randomly assigned to 7 groups (n=10 in each): Control rats and
      rats treated with low-dose L-NAME (40 mg/kg body weight/day) starting from
      gestational day (GD) 9, medium-L-NAME (75 mg/kg body weight/day) starting from GD
      9 (9D ML group), high-dose L-NAME (125 mg/kg body weight/day) starting from GD 9,
      low-dose L-NAME starting from GD 10, medium-dose L-NAME starting from GD 10 and
      high-dose L-NAME starting from GD 10. Blood pressure (BP), 24-h proteinuria,
      fetal intrauterine growth, histopathological changes, the plasma soluble fms-like
      tyrosine kinase-1 (sFlt-1)/placental growth factor (PLGF) ratio and cytokine
      levels were evaluated. Elevated BP, increased urinary albumin excretion, severe
      endotheliosis, mesangial expansion and increased sFlt-1/PLGF ratios were observed
      in the experimental groups compared with the control group (P<0.05), particularly
      in the 9D ML group. The results of the present study may optimize the conditions
      of the previously established L-NAME-induced preeclampsia SD rat model and aid
      further study into the pathogenesis of preeclampsia.

PMID- 30112026
TI  - Application value of iterative reconstruction with CTA to intractable headache
      patients.
AB  - Application value of iterative reconstruction with computed tomographic
      angiography (CTA) in the patients with intractable headache was investigated. One
      hundred and eighty patients with headache, who were admitted and treated in
      Cangzhou Central Hospital, were selected to undergo CTA scan. The patients were
      divided into group A, B and C according to different scanning conditions and data
      reconstruction techniques. In group A, the scanning parameters were 120 kV and
      300 mA, and filtered back projection (FBP) algorithm was used for data
      reconstruction. In group B, the scan parameters were 100 kV and automatic
      milliamperes. Further, adaptive iterative dose reduction via three-dimensional
      processing (AIDR-3D) was used for data reconstruction. In group C, the scan
      parameters were 80 kV with automatic milliamperes, and AIDR-3D technique was
      utilized for data reconstruction. The CT value, noise, signal-to-noise ratio
      (SNR), contrast-to-noise ratio (CNR), subjective assessment score of image
      quality and radiation dose of the three groups of images were compared. There
      were significant differences in CT values, standard deviation (SD) values, SNRs
      and CNRs of different vessel segments and muscles among the three groups
      (P<0.05). The image assessment scores at the levels of the atlas and C7 vertebra
      as well as those of the brain parenchyma in the three groups had notable
      differences (P<0.05). However, they showed no differences at the level of the C4
      vertebra (P>0.05). Further, significant differences were observed in volume
      computed tomography dose index (CTDIvol), dose-length product (DLP) and effective
      dose (ED) (P<0.05). In conclusion, for patients with intractable headache, the
      image quality of the CTA scan using AIDR-3D reconstruction method showed better
      results over FBP reconstruction method. Further, best results were observed when
      the scan parameters were 100 kV, automatic milliamperes and the data
      reconstruction was performed by AIDR-3D.

PMID- 30112027
TI  - Evaluation of the predictive value of high sensitivity C-reactive protein in
      pregnancy-induced hypertension syndrome.
AB  - Relationship between serum high sensitive C-reactive protein (hs-CRP) and
      pregnancy-induced hypertension syndrome (PIH) was investigated. One hundred and
      twenty patients with PIH treated in the First People's Hospital of Chengdu (60
      cases of mild preeclampsia, 60 cases of severe preeclampsia) were enrolled in the
      study. The control group included 60 women with normal singleton pregnancy. Serum
      hs-CRP and microalbuminuria (mALB) levels were measured by an AU5800 automatic
      biochemical analyzer (Beckerman Coulter), and the risk factors were analyzed by
      ROC curve analysis. Patients with PIH had higher levels of serum hs-CRP and mALB
      than the control group (P<0.01). Serum hs-CRP and mALB levels in the severe
      preeclampsia group were significantly higher than those in the mild preeclampsia
      group (P<0.05). ROC curve analysis showed that hs-CRP was a factor of high-risk.
      Area under the curve was 0.943, and the 95% confidence interval was 0.848-0.974.
      Detection of serum hs-CRP in patients with PIH can provide references for the
      prediction of the severity of the disease, and higher level of hs-CRP indicates
      worse condition.

PMID- 30112028
TI  - Curative effect of artificial femoral head replacement and its effect on hip
      joint function and complications of senile patients with femoral
      intertrochanteric fracture.
AB  - Curative effect of artificial femoral head replacement on hip joint function and
      complications of elderly patients with femoral intertrochanteric fracture were
      investigated. Eighty patients who were operated for femoral intertrochanteric
      fractures operation were randomly divided into observation group (n=40) and
      control group (n=40). The observation group was treated with artificial femoral
      head replacement, while the control group received internal proximal femur
      locking plate fixation. In the observation group, the operation time was shorter
      than that in the control group (P<0.05). The intraoperative bleeding was less
      than that in the control group (P<0.05). The postoperative indwelling drainage
      time was shorter than that in the control group (P<0.05). Besides, at 3, 6 and 12
      months after operation, 10 m walking speed in the observation group was
      significantly higher than that in the control group (P<0.05). The 5-time sit
      stand time was shorter than that in the control group (P<0.05). At 1 week, 1
      month, 3, 6 and 12 months after operation, Harris hip joint scores and visual
      analogue scale scores in the observation group were both superior to those in the
      control group (P<0.05). Moreover, the total hospitalization time in the
      observation group was shorter than that in the control group. Time of walking on
      crutches and walking without crutches was earlier than that in the control group
      (P<0.05). The overall proportion of postoperative chronic pain, thrombosis and
      failed surgery in the observation group was significantly lower than that in the
      control group (P<0.05). Finally, physical and psychological scores in the
      observation group after intervention were obviously higher than those in the
      observation group before intervention and the control group after intervention
      (P<0.05). Artificial femoral head replacement is characterized by the short
      operation time, less intraoperative bleeding, fast postoperative recovery of
      joint function, low degree of pain and fewer complications in the treatment of
      senile femoral intertrochanteric fracture, which can improve the postoperative
      life quality of patients.

PMID- 30112029
TI  - Echinacoside suppresses dexamethasone-induced growth inhibition and apoptosis in
      osteoblastic MC3T3-E1 cells.
AB  - Glucocorticoids (GCs) are widely used to treat chronic diseases. Prolonged and/or
      overdose administration of GCs has many side-effects to human health including GC
      induced osteoporosis (GIOP). In this investigation, the objective was to assess
      the influence that echinacoside (ECH) exerts upon dexamethasone-treated murine
      osteoblastic MC3T3-E1 cells. We found that ECH (5, 10, 20 and 40 mg/l) inhibited
      dexamethasone (1,000 nM)-suppressed cell viability as demonstrated by Cell
      Counting Kit-8 (CCK-8) assay. The dose of 10 mg/l was selected for the following
      experiments because this dose had a better effect than the dose of 5 mg/l, and
      the doses >10 mg/l had a similar effect as this dose. ECH (10 mg/l) or pifithrin
      alpha (PFT-alpha) (a p53 inhibitor, 20 uM) suppressed dexamethasone-induced MC3T3
      E1 apoptosis as illustrated by Annexin V/propidium iodide (PI) double-labeling
      flow cytometry analysis. ECH or PFT-alpha treatment also alleviated
      dexamethasone's action of inhibiting Bcl-2 expression as well as dexamethasone's
      action of stimulating on the expression of p53 and Bax. Moreover, lentivirus
      mediated-p53 overexpression reversed the effects of ECH in dexamethasone-treated
      MC3T3-E1 cells, suggesting that ECH induced anti-apoptotic effects in
      dexamethasone-treated osteoblasts via p53-dependent pathway. In summary, ECH has
      a protective effect against osteoblastic cell apoptosis induced by dexamethasone,
      suggesting that ECH may have potentials for clinical application in the treatment
      of GIOP.

PMID- 30112031
TI  - Application value of expansive pedicle screw in the lumbar short-segment fixation
      and fusion for osteoporosis patients.
AB  - Clinical value of expansive pedicle screw in lumbar short-segment fixation and
      fusion for patients with osteoporosis was investigated. A total of 80 patients
      with lumbar compression fracture but without obvious nerve compression were
      selected and divided into the observation group (n=40) and the control group
      (n=40) using a random number table. The observation group used the expansive
      pedicle screw, and the control group received conventional pedicle screw fixation
      and bone graft fusion. In the observation group, the operation and
      hospitalization time after operation were shorter and the intraoperative bleeding
      amount was less than that in control group (p<0.05). At 1 week, 1, 3 and 6 months
      after operation, the observation group had better straight leg raising test
      (SLRT) scores, higher lower limb sensory scores but lower visual analogue scale
      (VAS) scores than control group (p<0.05). Besides, the proportions of
      postoperative infection, dural mater tear, nerve root injury and spinal cord
      injury during operation in the observation group were lower than those in the
      control group (p<0.05), and the bone graft fusion rates at 3 and 6 months after
      operation were obviously superior to those in control group (p<0.05). Moreover,
      after operation, the spinal stenosis rate in the observation group was lower than
      that in control group (p<0.05), the vertebral height ratio was larger than that
      in control group (p<0.05), and the Cobb's angle was smaller than that in the
      control group (p<0.05). In addition, there was a negative correlation between
      bone mineral density (BMD) and hospitalization time after operation in the
      observation group (p<0.05). In conclusion, the internal fixation with expansive
      pedicle screw for osteoporosis patients with lumbar compression fracture is
      characterized by short operation time, less intraoperative bleeding, few
      complications, quick recovery of postoperative neurological function and
      satisfactory surgical effect. However, reasonable intervention in osteoporosis is
      also necessary.

PMID- 30112030
TI  - The clinical significance of Mda-7/IL-24 and C-myb expression in tumor tissues of
      patients with diffuse large B cell lymphoma.
AB  - Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin's
      lymphoma in adults. Mda-7/IL-24 had been identified as a differentiation inducer
      of B phenotype lymphoma cells. Previous studies have revealed that knockdown of C
      myb also leads to the terminal differentiation of B cell lymphoma. The aim of the
      present study was to investigate the association between the expression of Mda
      7/IL-24 and C-myb, and their prognostic significance for DLBCL patients. The
      tumor tissues were collected from 72 cases of DLBCL patients and detected with
      reverse transcription-quantitative polymerase chain reaction, western blotting
      and immunohistochemistry assays. The results showed that, the expression of Mda
      7/IL-24 mRNA and protein was lower while the expression of C-myb was higher in
      DLBCL tissues, compared with the specimens of normal lymph node tissues.
      Furthermore, C-myb expression was negatively correlated with Mda-7/IL-24
      expression at mRNA and protein levels in DLBCL tissues. The expression of Mda
      7/IL-24 and C-myb in DLBCL tissues was associated with some clinicopathological
      parameters such as clinical stage, infiltration in bone marrow, Ki67 expression
      level in the tumor tissues and overall survival rates. These results indicated
      that low expression of Mda-7/IL-24, along with high expression of C-myb, are
      predictor for poor prognosis of DLBCL patients, suggesting that Mda-7/IL-24 and C
      myb may be potential targets for clinical treatment of DLBCL.

PMID- 30112032
TI  - MIST1 regulates SNAI1 and acts through the PTEN/AKT signaling axis to promote
      anoikisresistance in human melanoma cells.
AB  - Cutaneous malignant melanoma (CMM) is one of the most dangerous types of skin
      cancer. The prognosis of CMM patients with ulcers, regional lymph node metastasis
      or organ metastasis is poor. In this process, resistance to anoikis is a critical
      step in tumor cell metastasis. Tumor cells survive in the vascular and lymphatic
      system through the escape of anoikis to finally form clones in the distal tissue.
      The present study revealed that muscle intestine and stomach expression 1
      (MIST1), a secreting cell-restricted transcription factor, was overexpressed in
      melanoma cells. At the same time, the expression of SNAI1 was also high. High
      expression of MIST1 and SNAI1 all contributed to melanoma cells bypassing
      anoikis. By changing the expression of MIST1, SNAI1 was indicated to be a
      downstream gene of MIST1. Chromatin immunoprecipitation and luciferase reporter
      gene technology revealed that MIST1 promoted the expression of SNAI1 by directly
      binding to its promoter region. Furthermore, inhibition of the
      phosphorylation/activity of Akt by LY294002 and knockdown of phosphatase and
      tensin homologue (PTEN) with simultaneous upregulation or knockdown of MIST1
      revealed that SNAI1 improved the phosphorylation of Akt by inhibiting the
      expression of PTEN. These results suggested that MIST1 hijacked the PTEN/AKT
      signaling pathway through directly regulating SNAI1 and affected the anoikis
      resistance capacity of melanoma cells.

PMID- 30112033
TI  - Matrine inhibits the proliferation and migration of lung cancer cells through
      regulation of the protein kinase B/glycogen synthase kinase-3beta signaling
      pathways.
AB  - Lung cancer is the leading cause of cancer-related mortality worldwide. Despite
      recent advances in treatment, lung cancer remains an incurable disease. Matrine,
      an active compound isolated from Sophora flavescens, has been demonstrated to
      inhibit proliferation and induce apoptosis of tumor cells. However, the
      protective effects and molecular mechanisms of matrine in lung cancer remain
      elusive. In the present study, the lung cancer cells H1299 and A549 were used to
      investigate how matrine affects the proliferation, migration and apoptosis of
      lung cancer cells in vitro. It was demonstrated that matrine is able to
      significantly suppress the proliferation and colony formation of lung cancer
      cells in vitro. Using cell apoptosis analysis, wound-healing and Transwell
      assays, it was demonstrated that matrine induced cellular apoptosis and inhibited
      the migration of lung cancer cells. Further experiments revealed that matrine
      significantly suppressed the phosphorylation of protein kinase B (Akt) and
      glycogen synthase kinase-3beta (GSK-3beta). The present results suggested that
      matrine inhibits lung cancer cell proliferation, and induces cell apoptosis by
      suppressing the Akt/GSK-3beta signaling pathway, which demonstrated that matrine
      may have therapeutic potential for lung cancer.

PMID- 30112034
TI  - Identification of potential key genes associated with severe pneumonia using mRNA
      seq.
AB  - This study aimed to identify the potential key genes associated with severe
      pneumonia using mRNA-seq. Nine peripheral blood samples from patients with severe
      pneumonia alone (SP group, n=3) and severe pneumonia accompanied with chronic
      obstructive pulmonary disease (COPD; CSP group, n=3), as well as volunteers
      without pneumonia (control group, n=3) underwent mRNA-seq. Based on the
      sequencing data, differentially expressed genes (DEGs) were identified by Limma
      package. Following the pathway enrichment analysis of DEGs, the genes that were
      differentially expressed in the SP and CSP groups were selected for pathway
      enrichment analysis and coexpression analysis. In addition, potential genes
      related to pneumonia were identified based on the information in the Comparative
      Toxicogenomics Database. In total, 645 and 528 DEGs were identified in the SP and
      CSP groups, respectively, compared with the normal controls. Among these DEGs, 88
      upregulated genes and 80 downregulated genes were common between the two groups.
      The functions of the common DEGs were similar to those of the DEGs in the SP
      group. In the coexpression network, the commonly downregulated genes (including
      ND1, ND3, ND4L, and ND6) and the commonly upregulated genes (including TSPY6P and
      CDY10P) exhibited a higher degree. In addition, 131 DEGs (including ND1, ND3,
      ND6, MIR449A and TAS2R43) were predicted to be potential pneumonia-related genes.
      In conclusion, the present study demonstrated that the common DEGs may be
      associated with the progression of severe pneumonia.

PMID- 30112035
TI  - Sustained localized reentry within the left atrial appendage as a mechanism of
      recurrent arrhythmia following atrial fibrillation ablation.
AB  - The current study investigated the electrophysiological characteristics and
      radiofrequency ablation in patients with localized reentry within the left atrial
      appendage during repeated ablation for recurrent atrial fibrillation (AF). A
      total of 76 patients (21 paroxysmal, 55 persistent) undergoing repeated catheter
      ablation for recurrent AF were enrolled in this study. Local reentry tachycardia
      within the left atrial appendage (LAA) was identified through combining
      activation and entrainment mapping. Left atriography was performed prior to
      radiofrequency ablation to identify the focus in the LAA. Three patients (1
      paroxysmal, 2 persistent) with sustained atrial tachycardias (ATs) were
      identified during repeated ablation in this cohort. Combined activation and
      entrainment mapping were applied to localize the reentry. Postpacing interval
      tachycardia cycle length differences were <30 msec at the possible site of
      reentry in varying segments with macro-reentry. This difference was only
      determined at the base of LAA for local reentry within the LAA. All 3 patients
      were free of atrial arrhythmias without any complications at the 6-month follow
      up following the ablation in the LAA. Combining activation and entrainment
      mapping were necessary in approaching ATs within the LAA. Performing entrainments
      in opposite segments of possible loops were valuable in precluding macro-reentry.
      Focal ablation was safe and effective in this cohort. Therefore localized reentry
      within the LAA was not uncommon during repeat AF ablation. The present study may
      thus provide valuable information for clinicians to manage this type of
      arrhythmia.

PMID- 30112038
TI  - Dexmedetomidine on autophagy of hippocampal neurons in aged rats under
      sevoflurane anesthesia.
AB  - Dexmedetomidine is a highly-selective alpha adrenergic receptor agonist, widely
      used as an anesthesia adjuvant drug in clinic. Effects of dexmedetomidine on
      autophagy of hippocampal neurons and cognitive dysfunction in aged rats under
      sevoflurane anesthesia were investigated. Sixty healthy Sprague-Dawley (SD) rats
      aged 4-6 months of either sex, weighing 150-200 g were selected and randomly
      divided into control group (n=10), sevoflurane group (n=25) and dexmedetomidine +
      sevoflurane group (compound group, n=25). The control group was inhaled with 60%
      O2 for 6 h, the sevoflurane group was inhaled with 3.4-3.6% sevoflurane for 6 h,
      and the compound group was treated with intraperitoneal injection of 4 ug/kg
      dexmedetomidine 1 h before the inhalation of sevoflurane. Five rats were taken
      from each group 1 h before sevoflurane anesthesia (T1), immediately after
      anesthesia (T2), 12 h after anesthesia (T3) and 24 h after anesthesia (T4),
      respectively. The expression levels of microtubule-associated protein 1 light
      chain 3-I (LC3-I), LC3-II and Beclin-1 were detected via western blotting, and
      the LC3-II/LC3-I value was calculated. Moreover, Morris water maze test was
      performed for the five rats in each group 5 weeks after anesthesia to detect the
      cognitive function; the escape latency, times across platform and swimming time
      in target quadrant were recorded. The levels of LC3-I, LC3-II and Beclin-1 in
      hippocampal neurons and LC3-II/LC3-I value in sevoflurane group at T2 were
      significantly higher than those at T1, and they reached the peak at T3, but were
      decreased at T4 (P<0.05); the levels of proteins and LC3-II/LC3-I value in
      compound group at T2 were significantly higher than those at T1 and reached the
      peak, and remained unchanged at T3-T4; besides, the level of proteins and LC3
      II/LC3-I values in compound group at T2-T4 were obviously lower than those in
      sevoflurane group (P<0.05). In sevoflurane group, the escape latency was
      prolonged, the times across platform were reduced and the swimming time in target
      quadrant was shortened compared with those in control group (P<0.05); these
      parameters were significantly improved in compound group compared with those in
      sevoflurane group and control group (P<0.05). In conclusion, dexmedetomidine can
      improve the cognitive dysfunction in aged rats under sevoflurane anesthesia,
      which is related to the decreased autophagy of hippocampal neurons.

PMID- 30112037
TI  - Mesenchymal stem cells and CXC chemokine receptor 4 overexpression improved the
      therapeutic effect on colitis via mucosa repair.
AB  - The present study intended to observe the homing capability and therapeutic
      effect of CXC chemokine receptor 4 (CXCR-4) gene overexpressed bone marrow
      mesenchymal stem cells (BMSCs) on colitis, and to study the possible mechanisms
      involved. BMSCs were derived from male BALB/c mice and CXCR-4 gene was
      transfected into BMSCs by the utilization of the lentiviral vector. The
      expression of CXCR-4 gene was analyzed and the biological characteristics, and
      vitality of BMSCs and CXCR-4 gene overexpressed BMSCs (CXCR-BMSCs) were detected.
      The chemotaxis assay was performed to investigate migration in vitro. Colitis was
      induced by TNBS in female BALB/c mice. BMSCs and CXCR-BMSCs were injected into
      experimental models intravenously. The homing of cells was confirmed by
      fluorescence observation and Sry gene detection. Clinical manifestation and
      histological changes were also evaluated. The expression levels of occludin and
      vascular endothelial growth factor (VEGF) were detected to measure mucosal
      repair. Furthermore, CXCR-4 gene was successfully transfected into BMSCs by the
      utilization of lentiviral vector. Results indicated that overexpression of CXCR-4
      gene did not influence the biological characteristics and vitality of BMSCs, but
      enhanced the capability of migration and homing of BMSCs in vitro and in vivo.
      Notably, CXCR-BMSCs had an improved effect on treating colitis, and the
      expression levels of Occludin and VEGF were higher. The results suggested that
      overexpression of CXCR-4 gene may enhance BMSC homing to damaged intestinal
      mucosa and their curative effect on colitis. The present findings indicated that
      using lentiviral vector to transfect CXCR-4 gene into BMSCs may be a potential
      method to improve the outcomes of BMSCs treatment on inflammatory bowel disease.

PMID- 30112039
TI  - Research on the effect of cytokine concentration on the immune level and survival
      conditions of elderly patients with sepsis.
AB  - The present study was carried out to investigate the effect of cytokine (CK)
      concentrations on the immune phenotype and survival conditions of elderly
      patients with sepsis. A total of 112 elderly patients with sepsis who were
      admitted to The Affiliated Hospital of Medical School, Ningbo University for
      treatment between June 2015 and June 2017 were enrolled as the subjects.
      According to each patient's condition, they were divided into the mild sepsis
      group (n=68) and the severe sepsis group (n=44). Additionally, a further 60
      patients without sepsis who were admitted to the Intensive Care Unit (ICU) of
      this hospital during the same period were recruited as the control group. The
      levels of CK, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-8,
      procalcitonin (PCT), endothelin-1 (ET-1) and IL-10 were detected, and the
      assessment system for immune levels was established. The levels of TNF-alpha, IL
      6, IL-8, PCT, ET-1 and IL-10 in the serum of patients in the mild and severe
      sepsis groups were significantly higher than those in the control group (P<0.05),
      and the levels in the severe sepsis group were significantly higher than those in
      the mild sepsis group (P<0.05). Among the 112 sepsis patients, there were 30
      mortalities (26.79%) within 30 days, of which the levels of TNF-alpha, IL-6, IL
      8, PCT, ET-1 and IL-10 were significantly higher than those in the surviving
      patients (P<0.05). Between the mild and severe sepsis groups, as well as the
      number of mortalities and surviving patients, there were statistically
      significant differences when comparing the immunological phenotypes (P<0.05).
      These findings indicated that the levels of TNF-alpha, IL-6, IL-8, PCT, ET-1 and
      IL-10 were associated with the condition and prognosis of elderly patients with
      sepsis, and the assessment system for immune levels based on the levels of these
      indicators was conducive to the stipulation of individualized immune regulation
      procedure and prognostic evaluation of sepsis.

PMID- 30112036
TI  - Comprehensive integrated analysis of gene expression datasets identifies key anti
      cancer targets in different stages of breast cancer.
AB  - Breast cancer is one of the primary threats to women's health worldwide. However,
      the molecular mechanisms underlying the development of breast cancer remain to be
      fully elucidated. The present study aimed to investigate specific target gene
      expression profiles in breast cancer tissues in general and in different breast
      cancer stages, as well as to explore their functions in tumor development. For
      integrated analysis, a total of 5 gene expression profiling datasets for 3
      different stages of breast cancer (stages I-III) were downloaded from the Gene
      Expression Omnibus of the National Center for Biotechnology Information. Pre
      processing of these datasets was performed using the Robust Multi-array Average
      algorithm and global renormalization was performed for all studies.
      Differentially expressed genes between breast cancer patients and controls were
      estimated using the empirical Bayes algorithm. The Database for Annotation,
      Visualization and Integrated Discovery web server was used for analyzing the
      enrichment of the differentially expressed genes in Gene Ontology terms of the
      category biological process and in Kyoto Encyclopedia of Genes and Genomes
      pathways. Furthermore, breast cancer target genes were downloaded from the
      Thomson Reuters Integrity Database. We merged these target genes with the genes
      in breast cancer datasets. Analysis of anti-breast cancer gene networks was
      performed using the Genome-scale Integrated Analysis of Gene Networks in Tissues
      web server. The results demonstrated that the normal functions of the cell cycle,
      cell migration and cell adhesion were altered in all stages of breast cancer.
      Furthermore, 12 anti-breast cancer genes were identified to be dysregulated in at
      least one of the three stages. Among all of these genes, ribonucleotide reductase
      regulatory subunit M2 (RRM2) exhibited the highest degree of interaction with
      other interacting genes. Analysis of the network interactions revealed that the
      transcription factor of RRM2 is crucial for cancer development. Other genes,
      including mucin 1, progesterone receptor and cyclin-dependent kinase 5 regulatory
      subunit associated protein 3, also exhibited a high degree of interaction with
      the associated genes. In conclusion, several key anti-breast cancer genes
      identified in the present study are mainly associated with the regulation of the
      cell cycle, cell migration, cell adhesion and other cancer-associated cell
      functions, particularly RRM2.

PMID- 30112041
TI  - Naringenin inhibits NG-nitro-L-arginine methyl ester-induced hypertensive left
      ventricular hypertrophy by decreasing angiotensin-converting enzyme 1 expression.
AB  - Naringenin (NGN) is a natural flavonoid that exerts antiinflammatory, antioxidant
      and cardioprotective effects. The present study investigated the effects of NGN
      on left ventricular hypertrophy in rats with NG-nitro-L-arginine methyl ester (L
      NAME)-induced hypertension, and sought to determine the underlying mechanism of
      action. The rats received the following by gavage daily for 56 days: L-NAME (50
      mg/kg/day) + NGN (100 mg/kg/day), L-NAME (50 mg/kg/day) + saline, or saline +
      saline. Blood pressure, heart rate and body weight were recorded. Left
      ventricular hypertrophy was assessed by echocardiography and hematoxylin-eosin
      staining. Angiotensin II (Ang II) and angiotensin-converting enzyme 1 (ACE1),
      which serve a pivotal role in cardiac remodeling, were evaluated by ELISA,
      reverse transcription-quantitative polymerase chain reaction and western blot
      analysis. NGN had no significant effect on body weight, heart rate or blood
      pressure. The extent of left ventricular hypertrophy in the L-NAME + NGN group
      was lower than in the L-NAME + saline group on day 56. NGN decreased Ang II and
      ACE1 protein levels in myocardial tissues. In conclusion, Ang II and ACE1
      expression in cardiac tissue was inhibited by NGN in L-NAME-treated rats, which
      may contribute to the inhibitory effects of NGN on left ventricular hypertrophy
      that is induced by pressure overload.

PMID- 30112040
TI  - Association analysis of dietary habits with gut microbiota of a native Chinese
      community.
AB  - Environmental exposure, including a high-fat diet (HFD), contributes to the high
      prevalence of colorectal cancer by changing the composition of the intestinal
      microbiota. However, data examining the interaction between dietary habits and
      intestinal microbiota of the Chinese population is sparse. We assessed dietary
      habits using a food frequency questionnaire (FFQ) in native Chinese community
      volunteers. Based on the dietary fat content determined using the FFQ, the
      volunteers were divided into HFD group (>=40% of dietary calories came from fat)
      or low-fat diet (LFD) group (<40%). Fecal and colonic mucosal microbiota
      composition was determined using 16S rDNA based methods. In stool matter of HFD
      group, Prevotella and Abiotrophia showed significantly higher abundance, whereas
      unclassified genus of S24-7 (family level) of Bacteroidetes, Gemmiger,
      Akkermansia and Rothia were less abundant. On colonic mucosal tissue testing,
      unclassified genus of S24-7 showed significantly higher abundance while
      Bacteroides, Coprobacter, Abiotrophia, and Asteroleplasma were less abundant in
      HFD group. A high fat and low fiber diet in a native Chinese community may
      partially contribute to changes of intestinal microbiota composition that may
      potentially favor the onset and progression of gastrointestinal disorders
      including inflammatory, hyperplastic and neoplastic diseases.

PMID- 30112042
TI  - Novel compound heterozygous mutations in low density lipoprotein receptor gene
      causes a severe phenotype in a Chinese hypercholesterolemia family.
AB  - Mutations in the low density lipoprotein receptor (LDLR) gene serve a causative
      role in the pathophysiology of familial hypercholesterolemia (FH), a common
      autosomal inherited disorder characterized by abnormal lipid metabolism. The aim
      of the present study was to investigate genetic defects in a Chinese family with
      FH. Clinical features and family histories were collected, as were the results of
      various laboratory tests, including determinations of serum lipid concentrations,
      ultrasonography and angiography results. Potential mutations in LDLR were
      screened using direct polymerase chain reaction (PCR) sequencing. Multiple
      sequence alignments, structure and hydrophobicity predictions were performed in
      silico. Novel compound heterozygote mutations in LDLR of the proband were
      identified, with a Trp577Term-bearing maternal allele and a Pro685Leu-bearing
      paternal allele. The proband, a 27-year-old male, had severe and diffuse coronary
      stenosis and non-ST segment elevation myocardial infarction, as well as multiple
      skin xanthomas and high serum lipid levels. The allele-dosage-dependent clinical
      features, including hypercholesterolemia and peripheral arterial atherosclerosis,
      were observed in the proband and the other heterozygous patients. Therefore, the
      coexistence of Pro685Leu and Trp577Term mutations in LDLR is a novel compound
      heterozygosis in Chinese patients and may lead to a severe FH phenotype. The
      explanation for the existence of compound heterozygous mutations instead of
      homozygous mutations in this particular family requires further study.

PMID- 30112043
TI  - Ultrasonic diagnosis combined with targeted ultrasound contrast agent improves
      diagnostic sensitivity of ultrasonic for non-small cell lung cancer patients.
AB  - Non-small cell lung cancer (NSCLC) is one of the most prevalent human cancers,
      which is known for local growth, easily migration, long-distance invasion and
      reoccurrence. Targeted ultrasound (US) contrast combined with ultrasound for lung
      cancer diagnosis has been applied in the clinic. In the present study, a novel
      targeted ultrasound contrast agent containing chistosan/Fe3O4-parceled bispecific
      antibody (TcBab) targeting carcino-embryonic antigen, vascular endothelial growth
      factor receptor was introduced, and the diagnostic accuracy and sensitivity was
      investigated in patients with NSCLC. A total of 384 patients with suspected NSCLC
      were recruited to investigate the accuracy of TcBab-ultrasound (TcBab-US) and
      ultrasound. Results demonstrated that TcBab-US improved sensitivity and may
      provide a novel protocol for diagnosing tumors in patients with suspected NSCLC
      at an early stage. Data analysis demonstrated that TcBab-US diagnosed 154
      suspected patients with NSCLC, whereas ultrasound only diagnosed 84 suspected
      patients with NSCLC out of a total of 384 patients with suspected NSCLC (P<0.01).
      A dosage experiment revealed that the optimal dose of TcBab was 5 mg/kg for NSCLC
      patients. Pharmacodynamics analysis showed that TcBab may be metabolized within
      16 h in serum of patients. Notably, early diagnosis determined by TcBab-US
      contributed to improvement of survival for NSCLC patients as determined by a
      comparison of the survival rate with the survival rate of patients who did not
      receive TcBab (P<0.05). In conclusion, these investigations suggested that TcBab
      improves the accuracy and diagnostic confidence of ultrasonic for the diagnosis
      of early-stage NSCLC, and may have potential application value in the clinic.

PMID- 30112046
TI  - Activated protein C inhibits lung injury induced by LPS via downregulating MAPK
      signaling.
AB  - The aim of the present study was to investigate the effect and the underlying
      mechanism of activated protein C (APC) in lipopolysaccharide (LPS) induced lung
      injury, as well as the potential mechanism. According to the treatment, 50 rats
      were randomly divided into 5 groups: Control, model (LPS), low-dose group [LPS +
      0.1 mg/kg recombined human activated protein C (rhAPC)], median-dose group (LPS +
      0.3 mg/kg rhAPC) and high-dose group (LPS + 0.5 mg/kg rhAPC). Then, inflammation
      in the lung was assessed using hematoxylin and eosin (H&E) staining. Following
      the collection of bronchoalveolar lavage fluid (BALF), the number of leukocytes
      and neutrophils in BALF was counted, and superoxide dismutase (SOD) activity was
      assessed, as well as the expression levels of interleukin (IL)-1beta, IL-6 and
      tumor necrosis factor (TNF)-alpha using ELISA. Subsequently, the expression and
      phosphorylation of P-38, extracellular signal-regulated kinase (Erk)-1/2, and c
      Jun N-terminal kinase (JNK) were estimated using western blotting. Based on H&E
      staining, rhAPC markedly suppressed inflammatory infiltration in the lung induced
      by LPS in a dose-dependent manner. In addition, rhAPC also significantly
      attenuated the accumulation of leptocytes and neutrophils, and the reduction of
      SOD in BALF induced by LPS in a dose-dependent manner. rhAPC also significantly
      attenuated the elevation of IL-1beta, IL-6 and TNF-alpha in BALF induced by LPS
      in a dose-dependent manner. Further mechanistic analysis revealed that rhAPC
      treatment could evidently attenuate the phosphorylation levels of P-38, Erk1/2
      and JNK in the lung induced by LPS in a dose-dependent manner. In conclusion, APC
      significantly alleviated the lung inflammation induced by LPS by downregulating
      the phosphorylation of P-38, ERK1/2 and JNK.

PMID- 30112044
TI  - Melatonin alleviates liver steatosis induced by prenatal dexamethasone exposure
      and postnatal high-fat diet.
AB  - Prenatal exposure to glucocorticoids is associated with negative health
      consequences for the offspring that persist into adulthood, including liver
      steatosis. Melatonin has previously been demonstrated to suppress liver steatosis
      and oxidative stress in humans with non-alcoholic fatty liver disease and in
      animal models of obesity. The present study aimed to determine whether melatonin
      protects against liver steatosis induced by prenatal dexamethasone exposure
      followed by postnatal high-fat diet. Pregnant Sprague-Dawley rats at gestational
      days 14-21 were administered dexamethasone (0.1 mg/kg/day) or saline via
      intraperitoneal injection. The offspring were then divided into five groups, as
      follows: Vehicle, postnatal high-fat diet (VHF), prenatal dexamethasone exposure
      (DEX), prenatal dexamethasone exposure + postnatal high-fat diet (DHF), and
      prenatal dexamethasone exposure + postnatal high-fat diet + melatonin (DHFM)
      group. Following vehicle or dexamethasone exposure of the maternal rats, the
      offspring rats in the VHF, DHF and DHFM groups received a high-fat diet (58% fat)
      between weaning and 6 months of age. In the DHFM group, melatonin was
      administered to the mothers from gestational days 14-21 until weaning. The
      offspring continued to receive melatonin until they were sacrificed at 6 months
      old. Oil Red O staining demonstrated stronger intensity in the DHF group compared
      with that in the other four groups. Western blot analysis also revealed higher
      levels of cleaved caspase-3, tumor necrosis factor-alpha (TNF-alpha), suppressor
      of cytokine signaling 3 (SOCS3) and malondialdehyde (MDA), as well as reduced
      expression of manganese superoxide dismutase (MnSOD) and phosphoinositide 3
      kinase (PI3K) in the DHF group compared with the vehicle and DHFM groups. In
      addition, melatonin reduced the Oil Red O staining intensity and the levels of
      cleaved caspase-3, TNF-alpha, SOCS3 and MDA, while it increased the MnSOD and
      PI3K levels, in the DHFM group compared with the DHF group. In conclusion,
      postnatal high-fat diet aggravated the prenatal dexamethasone-induced liver
      steatosis in adult rat offspring via inflammation, oxidative stress and cellular
      apoptosis, which may be ameliorated by prenatal melatonin therapy.

PMID- 30112045
TI  - Liver-targeted delivery of liposome-encapsulated curcumol using galactosylated
      stearate.
AB  - Liver-targeted drug delivery improves the efficacy of anti-liver cancer agents
      and reduces systemic toxicity by limiting the bioavailability of these drugs to
      within tumors. Liver targeting reagents with galactose residues, which
      selectively combine to asialoglyco protein receptors, have previously been used
      to improve liposome-encapsulated drug accumulation within liver cells. They lead
      to a reduction in liver cancer cell growth and have been used to cure certain
      hepatic diseases. In the present study, curcumol, which is the primary active
      component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in
      galactosylated-liposomes to enhance its anti-liver cancer efficacy.
      Galactosylated-liposomes and normal liposomes were labeled with propidium iodide.
      Galactosylated-liposomes with increasing concentrations of galactosylated
      stearate (Gal-s) had a notably increased level of uptake in HepG2 cells
      (hepatoblastoma) compared with SGC-7901 (gastric cancer) and A549 (non-small cell
      lung cancer) cells. When the percentage of Gal-s reached 20%, liposome uptake
      plateaued. In the in vitro anti-liver cancer experiment, the anti-liver cancer
      efficacy of galactosylated-curcumol-liposomes increased significantly more
      compared with normal curcumol liposomes and free curcumol as indicated by cell
      survival rate and lactate dehydrogenase release rate. Collectively, these results
      demonstrate that galactosylated-liposomes are able to enhance the in vitro liver
      targeting effect and anti-liver cancer efficacy of curcumol.

PMID- 30112047
TI  - Copeptin level in the early prediction of cardiorenal syndrome in rats.
AB  - Copeptin (CPP) has been considered as a useful marker for prediction of prognosis
      in heart diseases. However, CPP has not been investigated sufficiently in
      cardiorenal syndrome (CRS). The present study aimed to investigate the value of
      CPP level in predicting CRS in rats with partial nephrectomy combined with
      myocardial infarction (SNX + MI). A total of 60 male Sprague-Dawley rats were
      used to establish the CRS model by partial nephrectomy combined with MI. The rats
      were randomly divided into blank control (CK), SNX, MI and CRS groups. Changes in
      serum and urine CPP concentrations, hemodynamics, blood pressure, and renal
      function were examined 1-5 weeks after modeling. The predictive values of CPP in
      the occurrence of CRS in rats were evaluated using receiver operating
      characteristic (ROC) curve. The results showed that serum CPP in the CRS group in
      1-5 weeks and urine CPP in 3 weeks after modeling increased significantly
      compared with the CK group. Also, serum B-type natriuretic peptide (BNP) in 1 and
      3 weeks and urine BNP in 4-5 weeks after modeling increased significantly. No
      correlation was found between serum or urine CPP, BNP and BUN levels 1 week after
      modeling in the CRS group. The ROC curve analysis showed that the area under the
      curve of CRS predicted by serum CPP at 1 week was 0.908 with 56.59 pg/ml as the
      cutoff point, and its diagnostic sensitivity and specificity were 87.5 and 80.0%,
      respectively. To conclude, SNX + MI may be used to establish CRS rat model with
      cardiac and renal damage. Serum CPP may serve as a specific biomarker for the
      early prediction of CRS.

PMID- 30112048
TI  - Diagnostic implications of MOG/AQP4 antibodies in recurrent optic neuritis.
AB  - The present study aimed to detect myelin oligodendrocyte glycoprotein (MOG) and
      aquaporin-4 (AQP4) antibodies in serum specimens of patients with recurrent optic
      neuritis (RON) through establishing 293 cells with stable expression of MOG and
      the complete genomic sequence as the substrate using a cell-based assay (CBA).
      Furthermore, the clinical features of MOG antibody-positive recurrent optic
      neuritis (MOG-RON) were assessed. A total of 43 RON patients admitted to Beijing
      Tongren Hospital from December 2014 to May 2015 were enrolled, including 11 males
      and 32 females. The serum was collected from all patients, and the MOG and AQP4
      antibodies were detected via the CBA. According to the results, the 43 patients
      were divided into four groups, namely the MOG antibody-positive group (n=11), the
      AQP4 antibody-positive group (n=20), the MOG/AQP4 antibody-positive group (n=1)
      and the MOG/AQP4 antibody-negative group (n=11). Clinical data were collected and
      all patients were followed up for 6 months, with parameters observed including
      the visual acuity, visual field and ocular fundus. The differences in the
      demographics, clinical features, characteristics of imaging examination, vision
      at onset and visual function recovery at 6 months after treatment were compared
      among the different groups. The characteristics of MOG antibody-positive RON were
      summarized. Of the 43 RON patients, 2.33% was both MOG and AQP4 antibody
      positive, 27.91% were MOG antibody-positive. Compared with the AQP4-RON patients,
      there were relatively less MOG-RON patients (63.6 vs. 95.0%) and the canal
      segment and intracranial segment of the optic canal were less involved (P<0.05).
      The visual acuity at onset of MOG-RON was not inferior to that of AQP4-RON, and
      the visual recovery degree of MOG-RON was better (P<0.05). MOG antibody may be
      detected in the serum of certain RON patients, which have unique and different
      characteristics from AQP4 antibody-positive RON patients, so it may be used as a
      prognostic biomarker for RON. Furthermore, MOG antibody is present in the serum
      of patients with neuromyelitis optica spectrum disorders and may be a potential
      biomarker for these conditions.

PMID- 30112049
TI  - Exendin-4 protects INS-1 cells against palmitate-induced apoptosis through the
      IRE1alpha-Xbp1 signaling pathway.
AB  - The anti-apoptotic effect of the incretin analog, exendin-4 (EX-4) on pancreatic
      beta cells is mediated via the activation of protein kinase B (Akt) signaling,
      and its effect is partly produced through the inhibition of endoplasmic reticulum
      (ER) stress. However, the molecular mechanisms that underlie the effect of EX-4
      on the suppression of ER stress and the upregulation of Akt signaling are poorly
      understood. Inositol-requiring enzyme 1 (IRE1), a member of the ER-localized
      transmembrane protein family, activates its downstream transcription factor X-box
      binding protein 1 (XBP1) to mediate a key part of the cellular unfolded protein
      response in order to cope with ER stress. Using the clonal rat pancreatic beta
      cell line INS-1, the present study produced an in vitro model of ER stress using
      palmitate (PA) in order to determine whether the beneficial effect of EX-4 under
      ER stress was regulated by the IRE1alpha-Xbp1 signaling pathway. The results
      demonstrated that the reduction in ER stress and the activation Akt by EX-4 may
      be associated with the upregulation of IRE1alpha phosphorylation and the splicing
      of Xbp1 mRNA, which improved PA-reduced cell viability. This effect was partially
      abrogated by the knockdown of IRE1alpha with small interfering RNA. Additionally,
      cellular IRE1alpha was phosphorylated by the protein kinase A (PKA) associated
      with EX-4 and the activation of IRE1alpha, as IRE1alpha phosphorylation was
      attenuated by the inhibition of PKA with its inhibitor. In conclusion, the data
      identified the IRE1alpha-Xbp1 signaling pathway as an essential mediator that
      associates EX-4 with the intracellular mechanism that inhibits ER stress and
      activates Akt in order to regulate beta cell survival. This may provide important
      evidence for the use of EX-4 in treatments for type 2 diabetes.

PMID- 30112050
TI  - Compound Astragalus and Salvia miltiorrhiza extract inhibits hepatocarcinogenesis
      via modulating TGF-beta/TbetaR and Imp7/8.
AB  - Compound Astragalus and Salvia miltiorrhiza extract (CASE) is a Chinese herbal
      formula consisting of astragalosides, astragalus polysaccharide and salvianolic
      acids extracted from Astragalus membranaceus and Salvia miltiorhiza. Previous
      studies by our group have demonstrated that CASE effectively suppresses
      diethylinitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats via
      modulating transforming growth factor beta/Mothers against decapentaplegic
      (TGFbeta/Smad) signaling. To further elucidate the mechanism of CASE, the effects
      of CASE on TGF-beta1, the serine/threonine kinase receptors of TGF-beta [TGF-beta
      receptor type-I (TbetaRI) and TbetaRII] and karyopherins [Importin 7 (Imp7) and
      Imp8], which are crucial for TGF-beta/Smad signaling in fibro
      hepatocarcinogenesis, were assessed in the present study using in vivo (DEN
      induced HCC in rats) and in vitro [TGF-beta1-stimulated rat myofibroblasts (MFBs)
      and HepG2 cells] models of fibro-hepatocarcinogenesis. Hematoxylin and eosin
      staining revealed that CASE may suppress inflammatory reactions and fibrosis in
      HCC as well as increasing the differentiation of HCC cells. Positive TGF-beta1
      staining was increased in HCC nodule areas and in adjacent normal liver tissues
      in DEN-treated rats, while TbetaRI staining was increased only in normal adjacent
      liver tissues. The elevated expression of TGF-beta1, TbetaRI and TbetaRII was
      suppressed by CASE. CASE treatment also reduced glutathione S-transferase P 1 and
      Imp7/8 protein expression in fibro-hepatocarcinogenesis. In vitro experiments
      confirmed that CASE was able to decrease the expression of TbetaRI and TbetaRII
      in TGF-beta1-stimulated MFBs and HepG2 cells. These results indicate that the
      anti-HCC effect of CASE may be achieved by mediating TGF-beta/TbetaR and Imp7/8
      protein expression, suggesting that CASE has multiple targets in HCC treatment.

PMID- 30112051
TI  - Effects of downregulated expression of microRNA-187 in gastric cancer.
AB  - microRNAs (miRNAs) are involved in cancer development and progression, and have
      regulatory roles as tumor suppressors or oncogenes. Although aberrant expression
      of miR-187 has been observed in several types of cancer, its pathophysiological
      role and relevance to tumorigenesis in gastric cancer (GC) remains unknown. In
      the present study, the expression and biological role of miR-187 was investigated
      in 32 specimens of GC tissues and their adjacent non-tumorigenic controls, and
      the association between miR-187 expression and clinical features of GC were
      analyzed further. Kaplan-Meier survival curves determined the clinical
      significance of miR-187 expression in GC. Following transfection with miR-187
      mimics, the biological functions of miR-187 were determined by cell proliferation
      and cell cycle assays. Moreover, following transfection with miR-187 mimics, the
      targets regulated by miR-187 were investigated using western blotting. Luciferase
      reporter assays confirmed whether miR-187 regulated MAD2 mitotic arrest deficient
      like 2 (MAD2L2) and stomatin (EPB72)-like 2 (STOML2) expression. The data of the
      present study revealed that miR-187 was significantly downregulated in GC
      compared with adjacent non-tumorigenic counterparts. Furthermore, decreased
      expression of miR-187 correlated with cell differentiation (P<0.05), TNM staging
      (P<0.05) and poor prognosis in GC patients. Functional studies indicated that miR
      187 overexpression evidently inhibited MGC-803 cell proliferation in vitro and
      altered the cell cycle by arresting cells in the G0/G1 phase. In addition, the
      luciferase assay and western blotting revealed that MAD2L2 and STOML2 were
      targeted by miR-187. In conclusion, it is suggested that miR-187 functions as a
      tumor suppressor in GC, and is important in the development and progression of
      GC. Moreover, miR-187 may be a potential biomarker and therapeutic target in GC.

PMID- 30112052
TI  - Silence of IGFBP7 suppresses apoptosis and epithelial mesenchymal transformation
      of high glucose induced-podocytes.
AB  - Insulin-like growth factor-binding protein 7 (IGFBP7) has been identified as a
      secreted protein associated with a number of cellular processes. However, the
      specific regulatory mechanisms of IGFBP7 on podocytes of diabetic nephropathy
      (DN) are yet to be elucidated. In the present study, podocytes were identified
      initially via an immunofluorescence assay using an anti-synaptopodin antibody. It
      was subsequently demonstrated that glucose promoted podocyte proliferation in a
      time- and dose-dependent manner via MTT assay. In addition, IGFBP7 expression was
      silenced in podocytes via siRNA, the effects of which were evaluated using
      western blotting and reverse transcription-quantitative polymerase chain
      reaction. It was demonstrated that silencing IGFBP7 inhibited apoptosis and
      epithelial mesenchymal transformation (EMT) of podocytes mediated by high glucose
      (HG). Transforming growth factor (TGF)-beta1/mothers against decapentaplegic
      homolog (Smad) signaling was associated with proliferation, apoptotic activities
      and EMT. Therefore, the expression levels of TGF-beta1/Smad pathway were
      detected, and it was observed that silencing IGFBP7 suppressed the TGF-beta1/Smad
      pathway in podocytes induced by HG. These findings suggested that IGFBP7 may
      serve as a potential therapeutic target for DN.

PMID- 30112053
TI  - Identification of key genes and pathways for esophageal squamous cell carcinoma
      by bioinformatics analysis.
AB  - The aim of the present study was to identify the differentially expressed genes
      (DEGs) in esophageal squamous-cellcarcinoma (ESCC) and provide potential
      therapeutic targets. The microarray dataset GSE20347 was downloaded from the Gene
      Expression Omnibus (GEO) database, and included 17 tissue samples and 13 normal
      adjacent tissue samples from patients with ESCC. A total of 22,277 DEGs were
      identified. A heat map for the DEGs was constructed with the Morpheus online tool
      and the top 200 genes (100 upregulated and 100 downregulated) were selected for
      further bioinformatics analysis, including analysis of gene ontology (GO) terms,
      Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, protein-protein
      interaction networks and Spearman's correlation tests. The results of the GO
      analysis indicated that the upregulated DEGs were most significantly enriched in
      membrane-bounded vesicles in the cellular component (CC) category, but were not
      significantly enriched in any GO terms of the categories biological process (BP)
      or molecular function (MF); furthermore, the downregulated DEGs were most
      significantly enriched in regulation of DNA metabolic processes, nucleotide
      binding and chromosomes in the categories BP, MF and CC, respectively. The KEGG
      analysis indicated that the downregulated DEGs were enriched in the regulation of
      cell cycle pathways. The top 10 hub proteins in the protein-protein interaction
      network were cyclin-dependent kinase 4, budding uninhibited by benzimidazoles 1,
      cyclin B2, heat shock protein 90AA1, aurora kinase A, H2A histone family member
      Z, replication factor C subunit 4, and minichromosome maintenance complex
      component 2, -4 and -7. These proteins are mainly involved in regulating tumor
      progression. The genes in the four top modules were mainly implicated in
      regulating cell cycle pathways. Secreted Ly-6/uPAR-related protein (SLURP) was
      the hub gene, and SLURP and its interacting genes were most enriched in the
      chromosomal part in the CC category, organelle organization in the BP category
      and protein binding in the MF category, and were involved in pathways including
      DNA replication, cell cycle and P53 signaling. The expression of SLURP-1 in
      fifteen patients with esophageal carcinoma was detected using quantitative
      polymerase chain reaction analysis, and the results indicated that SLURP-1
      expression was significantly decreased in the tumor samples relative to that in
      normal adjacent tissues. These results suggest that several hub proteins and the
      hub gene SLURP-1 may serve as potential therapeutic targets, and that gene
      dysfunction may be involved in the tumorigenesis of ESCC.

PMID- 30112054
TI  - General anesthesia combined with epidural anesthesia on the postoperative
      cognitive functions in pregnant women with dystocia.
AB  - Effects of general anesthesia combined with epidural anesthesia on the
      postoperative cognitive functions in pregnant women with dystocia were
      investigated. Postoperative cognitive functions of 84 dystocia pregnant women
      treated with cesarean section were retrospectively analyzed. Patients who
      received general anesthesia were included in group A (n=42), and those who
      received general anesthesia combined with epidural anesthesia were included in
      group B (n=42). Mean arterial pressure (MAP), heart rate (HR) and bispectral
      index (BIS) at different time-points after anesthesia in the two groups of
      patients were observed and compared. Recovery of anesthesia such as the recovery
      time of spontaneous breathing, recovery time of orientation and time of eye
      opening were observed and compared between two groups of patients. Mini mental
      state examination (MMSE) scores were obtained and compared between the the groups
      of patients at different time-points after operation. Three vital signs (MAP, HR
      and BIS) were not significantly different between group A and B at the same time
      point (P>0.05) and the maintenance of anesthesia was satisfactory. Compared with
      group A, postoperative recovery time of spontaneous breathing, recovery time of
      orientation and the time of eye opening in group B were all significantly shorter
      (P<0.05). In addition, MMSE scores of patients in group B, 2 and 12 h after
      operation were 24.33+/-1.61 and 26.41+/-1.83 points, respectively, which were
      significantly improved compared with those of patients in group A (20.45+/-1.58
      and 22.39+/-1.72 points, respectively) (P<0.05). In conclusion, recovery of
      postoperative cognitive functions in pregnant women with dystocia who received
      general anesthesia combined with epidural anesthesia was shorter to that of those
      who only received general anesthesia.

PMID- 30112055
TI  - Relevant analyses of pathogenic bacteria and inflammatory factors in neonatal
      purulent meningitis.
AB  - Pathogenic bacteria and inflammatory factors in neonatal purulent meningitis (PM)
      were investigated to explore the diagnostic value of inflammatory factors in PM,
      to clarify the etiology, and to provide evidence for rational clinical treatment.
      Seventy-four neonates who were diagnosed with PM and were bacteriogically
      positive in Daqing Longnan Hospital from January 2012 to December 2015 were
      retrospectively analyzed and used as observation group. Another 74 neonates
      simultaneously hospitalized with non-PM factors were selected as control group.
      The levels of C-reactive protein (CRP) and beta 2 microglobulin (beta2MG) in
      cerebrospinal fluid in pediatric patients were measured, and the separation
      culture and identification of pathogenic bacteria were carried out at the same
      time. The results showed that i) neonatal PM often lacked specific clinical
      manifestations; ii) high risk factors of neonatal PM included gestational age,
      body weight <2,500 g, neonatal asphyxia, premature rupture of membranes, and
      umbilical or pulmonary infection; iii) the levels of CRP and beta2MG in the
      cerebrospinal fluid in the neonatal PM group were significantly higher than those
      in the control group (P<0.05), and the neonatal PM group had obviously decreased
      levels of CRP and beta2MG in the cerebrospinal fluid after treatment compared
      with those before treatment (P<0.05); iv) the positive rate of Gram-negative
      bacilli (G-bacilli) showed an increasing trend year by year in the past 4 years.
      Seventy-four strains of bacteria were isolated from the cerebrospinal fluid in
      neonatal PM group, including 45 strains of Gram-positive cocci (G+cocci,
      accounting for 60.81%) and 29 strains of G-bacilli (accounting for 39.19%). Among
      them, the top three were Escherichia coli, coagulase-negative staphylococci (CNS)
      and Streptococcus. These findings indicated that for suspected PM pediatric
      patients with high risk factors, the inflammatory factors in cerebrospinal fluid
      and the etiology should be investigated via lumbar puncture as early as possible
      to confirm the diagnosis. Pathogenic bacteria of meningitis mainly are
      Escherichia coli, CNS and Streptococcus, and the characteristics of pathogenic
      bacteria should be considered during experiential medication. The incidence rate
      of PM due to Streptococcus has an upward tendency and great damage, needing to
      arouse high attention in clinic.

PMID- 30112056
TI  - Study on the clinical efficacy of specific phosphodiesterase inhibitor in
      patients with pulmonary hypertension due to left heart disease.
AB  - Pulmonary hypertension due to left heart disease (PH-LHD) is caused by left
      ventricular (LV) systolic and/or diastolic dysfunction and left heart valve
      disease. LV diseases lead to left ventricular filling pressure increases,
      pulmonary venous obstruction and pulmonary venous pressure increases, and thus to
      secondary PH. Exercise tolerance is lower and fatality rates are higher in
      patients with PH-LHD than those in subjects with normal pulmonary arterial
      pressure. In spite of the progress in the study of the mechanisms of PH-LHD in
      recent years, no specific treatment is currently available. The efficacy and
      safety of targeted therapies for pulmonary arterial hypertension remain to be
      fully established. In the present study, PH-LHD patients were treated with
      milrinone injection. It was concluded that milrinone significantly reduces
      pulmonary artery systolic pressure (PASP) in patients with PH-LHD, and
      significantly improves the cardiac structure, cardiac function and biochemical
      indexes. PASP was significantly correlated with the left atrial diameter, LV end
      diastolic diameter, LV ejection fraction, tricuspid annular plane systolic
      excursion, right ventricular fractional area change, N-terminal pro-B-type
      natriuretic peptide and hypersensitive C-reactive protein.

PMID- 30112057
TI  - Pregabalin treatment for neuropathic pain may damage intervertebral disc tissue.
AB  - The aim of the present study was to determine whether pharmaceutical preparations
      with pregabalin (PGB) as an active ingredient, which are widely prescribed by
      clinicians, exert toxic effects on human primary nucleus pulposus (NP) and
      annulus fibrosis (AF). Primary human cell cultures were obtained from intact
      (n=6) and degenerated (n=6) tissues resected from the two groups of patients.
      Different doses of PGB were applied to these cultures and cells were subjected to
      molecular analyses at 0, 24 and 48 h. Cell vitality, toxicity and proliferation
      were assessed using a spectrophotometer. The expression of chondroadherin (CHAD),
      a (member of the NP-specific protein family), hypoxia-inducible factor-1alpha
      (HIF-1alpha) and type II collagen (COL2A1) was measured using reverse
      transcription-quantitative polymerase chain reaction. The results revealed that
      cell intensity increased in a time-dependent manner and cell vitality continued
      in the cultures without pharmaceuticals. Cell proliferation was suppressed in the
      PGB-treated cultures independent from the dose and duration of application. PGB
      was demonstrated to suppress the expression of CHAD and HIF-1alpha. In contrast,
      COL2A1 gene expression was not revealed in any experimental group. The present
      study utilized an in vitro model and the PGB active ingredient used herein may
      not be representative of clinical applications; however, the results demonstrated
      that PGB has a toxic effect on NP/AF cell cultures containing primary human
      intervertebral disc tissue. In summary, the use of pharmacological agents
      containing PGB may suppress the proliferation and differentiation of NP/AF cells
      and/or tissues, which should be considered when deciding on an appropriate
      treatment regime.

PMID- 30112058
TI  - Effects of remote ischemic post-conditioning on platelet activation of AMI
      patients.
AB  - The recovery of ischemic myocardium blood perfusion is the main treatment option
      for acute myocardial infarction (AMI). However, this treatment option has
      multiple side effects that directly affect the quality of life of the patients.
      The activation of platelet function plays an important role in the occurrence,
      development and treatment of AMI. The aim of the present study was to analyze the
      effects of remote ischemic post-conditioning on platelet activation of AMI
      patients with primary PCI treatment and clinical prognosis. A total of 71
      patients with AMI were treated with primary percutaneous coronary intervention
      (PCI). They were randomly divided into control group (n=34) and observation group
      (n=37). The patients in the observation group were treated with remote ischemic
      post-conditioning. Further, flow cytometer was used to detect the platelet alpha
      granule membrane glycoprotein (CD62P) and the percentages of activated IIb/IIIa
      (PAC-1). The maximum platelet aggregation rate induced by adenosine diphosphate
      (ADP) and arachidonic acid (AA) was measured by light transmittance aggrometer.
      The incidence of major adverse cardiac events (MACE) was compared between the two
      groups during the follow-up period of 6 months. The percentage of CD62P (24 h
      after PCI) in the observation group was significantly lower than control group
      (P<0.05). Further, the incidence of MACE in the observation group was also lower
      than that of the control group (P<0.05). Remote ischemic post-conditioning could
      reduce the incidence of MACE in patients with AMI after primary PCI treatment.
      Moreover, the above observation may be related to the improvement of platelet
      CD62P activation.

PMID- 30112059
TI  - Human acellular amniotic membrane is adopted to treat venous ulcers.
AB  - Venous lower limb ulcers are very common and affect ~1% of the general
      population. The human acellular amniotic membrane (HAAM), which is isolated from
      the amniotic membrane (AM) via excluding the majority of cellular components, has
      lower antigenicity than the AM. The aim of the present study was to evaluate the
      effectiveness and safety of the HAAM, adopted to treat venous ulcers (VUs) of the
      lower extremities. The HAMM was isolated from the AM by the Stem Cells and Tissue
      Engineering laboratory at the West China Hospital of Sichuan University (Chengdu,
      China). HAMMs were grafted onto VUs in 4 patients, with follow-up evaluations
      performed on the 3rd day and at the end of the 1st, 2nd and 3rd week, and 2nd,
      3rd and 6th month after the HAAMs were applied. The size and depth of the VU
      (determined based on whether the depth of VU reaches the tibial plane), the
      proportion of granulation tissue (whether >50%) and the degree of secretion
      (measured by asessing the degree of satuation in the outer gauze) and infection
      (assessed qualitatively via the appearance of purulence or peripheral swelling)
      were assessed. Pain score was monitored at the same intervals using a visual
      analog scale. Complete epithelialization (healed tissue) occurred in 2 cases: The
      first at the end of the 3rd week and the second, at the 2nd month following HAAM
      induction. In one of the remaining cases, ulcer size was reduced by >60%; however
      the ulcer size of the remaining case only reduced by <20%. Overall, the size of
      ulcer in cases 1, 2, 3 and 4 decreased to 1.2*1.1 and 1.4*0.4 cm, 1.3*1.8 and
      2.3*1.4, respectively, with evident decreases in ulcer depth. The proportion of
      granulation tissue in each case was >50%. Furthermore, purulence and secretion
      completely disappeared in all 4 cases. Additionally, the medical cost of HAAM
      treatment is substantially lower than that of AM treatment, skin autografts and
      biomaterial transplantation, thus alleviating the patients' financial burden.
      These findings suggest that HAMM was highly effective in treating VUs in
      patients.

PMID- 30112060
TI  - Infantile neuroaxonal dystrophy caused by PLA2G6 gene mutation in a Chinese
      patient: A case report.
AB  - Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disorder.
      Phospholipase A2 group VI (PLA2G6) gene mutations have been identified in the
      majority of individuals with INAD. The present case report is on a Chinese female
      pediatric patient (age, 18 months) diagnosed with INAD with deafness. To date,
      only four cases of INAD with hearing loss have been reported, PLA2G6-association
      has not been investigated. Next-generation DNA sequencing technology was used to
      identify disease-associated genes and Sanger sequencing was applied to verify the
      mutation in the patient's pedigree. Two mutations were identified in the PLA2G6
      gene: c.1T>C (E2) and c.497 (E4) to c.496 (E4): Insert C. The distribution
      frequency of those mutations in the Single Nucleotide Polymorphism, HapMap, 1000
      Genomes and Exome Aggregation Consortium databases was 0. However, cases of INAD
      appear to be underreported, particularly those from China. The identification of
      two mutations in the present study suggests unique PLA2G6 mutations in Chinese
      patients, and greatly expands on the spectrum of known mutations in INAD
      patients.

PMID- 30112061
TI  - Role of vasodilator-stimulated phosphoprotein in human cytomegalovirus-induced
      hyperpermeability of human endothelial cells.
AB  - Atherosclerosis (AS) is a common chronic vascular disease and epidemiological
      evidence demonstrates that infection is closely associated with the occurrence of
      AS, including infection by human cytomegalovirus (HCMV) and Chlamydophila
      pneumoniae. The aim of the present study was to investigate the effect of HCMV
      AD169 infection on the barrier function of human umbilical vein endothelial cells
      (HUVECs) and to understand the role of vasodilator-stimulated phosphoprotein
      (VASP) during this process. In cultured HUVEC-CRL-1730 cells, knockdown of VASP
      expression with small interfering (si)RNA-VASP resulted in impaired cellular
      barrier function. Furthermore, knockdown of Ras-related C3 botulinum toxin
      substrate 1 (Rac1) using siRNA-Rac1 could induce downregulation of VASP
      expression in HUVEC-CRL-1730 cells. Additionally, following the infection of the
      cells by HCMV, cellular morphological alterations could be observed under an
      inverted microscope, the mRNA and protein levels of Rac1 and VASP were
      transiently reduced, and what appeared to be a time-dependent impairment of the
      barrier function was observed. Finally, transfection of siRNA-VASP or siRNA-Rac1
      into HCMV-infected HUVEC-CRL-1730 cells resulted in increased impairment of the
      cellular barrier function. Taken together, these data demonstrated that HCMV
      infection could induce impairment of the barrier function in monolayer HUVEC-CRL
      1730 cells via interference with Rac1/VASP expression.

PMID- 30112062
TI  - Relationship between ABCA1 gene polymorphism and lacunar infarction combined with
      arteriosclerosis in patients.
AB  - Adenosine triphosphate-binding cassette transporter A1 (ABCA1) gene polymorphism
      in lacunar infarction (LI) combined with arteriosclerosis was investigated. A
      total of 112 LI patients complicated with arteriosclerosis treated in Ningbo
      First Hospital from March 2015 to September 2016 were enrolled as observation
      group. At the same time, 342 healthy subjects were selected from physical
      examination center to serve as the control group. The ABCA1 gene polymorphism was
      detected via polymerase chain reaction-restriction fragment length polymorphism
      (PCR-RFLP), and the susceptibility of ABCA1 gene to LI complicated with
      atherosclerosis was studied. There were no significant differences in serum total
      cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a)
      [Lp(a)] between the two groups (P>0.05). Levels of triglyceride (TG) and
      apolipoprotein B (ApoB) in observation group were significantly higher than those
      in control group, but levels of ApoA-I and high-density lipoprotein cholesterol
      (HDL-C) were significantly lower in observation group than those in control group
      (P<0.05). There were no significant differences in the RR, RK and KK frequencies
      and allele frequency of ABCA1 R219K genotype between the two groups (P>0.05).
      Moreover, levels of HDL-C increased in the RR, RK and KK genotypes, but were not
      statistically significant (P>0.05). Levels of TG, TC, LDL-C, ApoA-I, ApoB and
      Lp(a) showed no significant differences among different genotypes of ABCA1 R219K
      (P>0.05). Results indicated that ABCA1 R219K polymorphism has no correlation with
      LI complicated with arteriosclerosis.

PMID- 30112064
TI  - An analysis on treatment effect of blue light phototherapy combined with Bifico
      in treating neonatal hemolytic jaundice.
AB  - This study aimed to discuss and evaluate the clinical effect of blue light
      phototherapy combined with bifico in treating neonatal hemolytic jaundice. One
      hundred and twenty cases with neonatal hemolytic jaundice were randomly divided
      into treatment group and control group, 60 cases in each group. Neonatal patients
      in the control group were treated with traditional treatment, including
      administration of enzyme inducer phenobarbital and blue light phototherapy for 8
      consecutive hours every day. Neonatal patients in the treatment group received
      bifico orally based on traditional treatment. Clinical effects of the two groups
      were observed after one course of treatment (7 days as one course). During the
      first course, serum bilirubin level in the treatment group treated with blue
      light phototherapy combined with bifico declined more rapidly (P<0.01) and more
      significantly (P<0.01) than that in the control group, and the mean time for
      eliminating jaundice was significantly reduced (P<0.05). The total effective rate
      was 91.67% in the treatment group, while that was 85.00% in the control group,
      which suggested that the treatment effect of the treatment group was better than
      that of the control group and the difference between the two groups was
      statistically significant (P<0.05). Compared with traditional treatment, the
      treatment effect of blue light phototherapy combined with bifico in treating
      neonatal hemolytic jaundice is significantly improved and the speed of
      eliminating jaundice is also higher. Thus, it is worthy to be applied in clinical
      practice.

PMID- 30112063
TI  - Detection of Treg/Th17 cells and related cytokines in peripheral blood of chronic
      hepatitis B patients combined with thrombocytopenia and the clinical
      significance.
AB  - Changes of regulatory T (Treg) cells and Th17 cells, and related cytokines in
      peripheral blood of patients with chronic hepatitis B combined with
      thrombocytopenia were investigated to explore the relationship with treatment
      outcomes. A total of 45 chronic hepatitis B patients combined with
      thrombocytopenia were selected in Heilongjiang Provincial Hospital from June 2015
      to December 2016. All patients were treated with prednisolone acetate + gamma
      globulins for 60 days. Treg cells and Th17 cells in peripheral blood were
      detected by flow cytometry, and IL-10, TGF-beta, IL-17, IL-21 and IL-22 in
      peripheral blood were detected by ELISA before and after treatment. No
      significant differences in the percentages of Treg and Th17, and levels of IL-10,
      TGF-beta, IL-17, IL-21 and IL-22 were found in non-responders (n=17, platelets
      <100*109/l) before and after treatment (P>0.05). After treatment, percentage of
      Treg was significantly increased (higher than that of non-responders) and
      percentage of Th17 was significantly decreased (lower than that of non
      responders) in responders (P<0.05). In addition, serum levels of IL-10 and TGF
      beta were significantly increased (higher than that of non-responders) and serum
      levels of IL-17, IL-21 and IL-22 were significantly decreased (lower than that of
      non-responders) in responders (P<0.05). The results showed that after treatment,
      the number of Treg cells was increased, the number of Th17 cells was decreased,
      the levels of anti-inflammatory factors IL-10 and TGF-beta were increased, and
      levels of pro-inflammatory factors IL-17, IL-21 and IL-22 were decreased in
      chronic hepatitis B patients combined with thrombocytopenia, indicating the
      decreased autoimmune response and improved thrombocytopenia. The changes were
      closely related to the complete response.

PMID- 30112065
TI  - Impact of proteasome inhibitor MG-132 on expression of NF-kappaB, IL-1beta and
      histological remodeling after myocardial infarction.
AB  - The aim of the present study was to investigate the impact of carbobenzoxy-Leu
      Leu-leucinal (MG-132) on myocardial remodeling in rats with myocardial infarction
      (MI) and investigate the possible underlying mechanisms. The rat model of MI was
      established, followed by administration of MG-132 (MG group), pyrrolidine
      dithiocarbamic acid (PDTC group) or normal saline (MI group) for 28 days. The
      expression of nuclear factor-kappaB (NF-kappaB) p65, interleukin 1beta (IL-1beta)
      and matrix metalloproteinase 2 (MMP-2), as well as the total volume of collagen
      and the ratio of type I/III collagen were then detected. Total collagen,
      including type I and III collagen, and the ratio of type I/III collagen were
      significantly increased in MI rats compared with those in the sham group
      (P<0.01), while it was significantly decreased in the PDTC and MG groups compared
      with that in the MI group (P<0.01). A similar trend was identified for the
      expression of NF-kappaB, IL-1beta and MMP-2, which was significantly increased in
      the MI group compared with that in the sham group (P<0.01), while it was
      significantly decreased in the MG and PDTC groups compared with that in the MI
      group (P<0.01). In conclusion, MG-132 was demonstrated to improve post-MI tissue
      remodeling, and the mechanism may be associated with the inhibition of NF-kappaB
      activation and the downregulation of inflammatory cytokines, such as IL-1beta.

PMID- 30112066
TI  - BMP7-overexpressing bone marrow-derived mesenchymal stem cells (BMSCs) are more
      effective than wild-type BMSCs in healing fractures.
AB  - Bone fractures are a worldwide public health concern. Previous studies have
      demonstrated that bone morphogenetic protein-7 (BMP7) gene transfer or
      mesenchymal stem cells (MSCs) transplantation may be a promising novel
      therapeutic approach. Therefore, the aim of the present study was to observe the
      effect of bone BMP7 transfer to MSCs on fracture healing. Bone marrow-derived
      MSCs (BMSCs) from New Zealand white rabbits were isolated and identified using
      flow cytometry. A recombinant BMP7 overexpressing adenovirus vector (Adv) was
      constructed and transfected into BMSCs. The expression of BMP7 was detected by
      reverse transcription-polymerase chain reaction, immunofluorescence and western
      blotting. The present study additionally investigated the effect of BMP7 on the
      differentiation capacity of BMSCs. Finally, tissue-engineered bone was created
      with support material to verify the effect of BMP7-BMSCs on fracture healing. The
      results demonstrated that the expression of BMP7 was increased at the mRNA and
      protein levels in BMSCs following transfection with BMP7 overexpressing Adv. The
      results additionally demonstrated that the expression of BMP7 enhanced the
      differentiation capacity of bone marrow mesenchymal stem cells and had a
      promotional effect on fracture healing. Overall, these data suggest that Adv-BMP7
      is useful for introducing foreign genes into BMSCs and will be a powerful gene
      therapy tool for bone regeneration and other tissue engineering applications in
      the future.

PMID- 30112067
TI  - Effect of TGF-beta1 on blood CD4+CD25high regulatory T cell proliferation and
      Foxp3 expression during non-small cell lung cancer blood metastasis.
AB  - Metastatic circulating tumor cells in non-small cell lung cancer (NSCLC)
      metastasis have been reported to be associated with an immune response. The
      present study aimed to provide a theoretical basis for the immunomodulatory
      processes during NSCLC blood metastasis. NSCLC blood and normal peripheral blood
      mononuclear cells (PBMCs) were collected. The quantity of cluster of
      differentiation (CD)4+CD25high regulatory T (Treg) cells and the intracellular
      forkhead box protein 3 (Foxp3) expression in CD4+CD25high Treg cells were
      determined by flow cytometry. Furthermore, the effect of transforming growth
      factor beta1 (TGF-beta1) on NSCLC blood CD4+CD25+ Treg cell proliferation was
      explored by activating blood mononuclear cells with an anti-CD3 monoclonal
      antibody, interleukin-2 and different doses of TGF-beta1. Reverse transcription
      quantitative polymerase chain reaction assays were used to detect the mRNA
      expression of Foxp3. Carboxyfluorescein succinimidyl ester staining was used to
      analyze the proliferation dynamics of lymphocyte subsets. Results indicate that
      the proportion of CD4+ T cells in the blood of patients with NSCLC was
      significantly higher compared with normal peripheral blood (P<0.01). Foxp3
      expression in NSCLC blood Treg cells was significantly decreased compared with
      normal peripheral blood (P<0.01). NSCLC blood mononuclear cells treated with TGF
      beta1 at 1, 5 and 25 ng/ml significantly induced Foxp3 expression in CD4+CD25+
      Treg cells compared with the control group (P<0.05). The proportion of CD4+CD25+
      Treg and CD8+ T cells were elevated in generation 6, 7, 8 after 6 days of TGF
      beta1 treatment compared with untreated cells. The proportion of CD4+CD25+ Treg
      and CD8+ T cells were elevated in generation 8, 9 and with TGF-beta1 treatment
      after 8 days compared with untreated cells. These results indicate that CD4+CD25+
      Treg cells proliferate at a greater rate compared with CD8+ T cells after 4, 6 or
      8 days of treatment. The proportion of CD4+CD25high Treg cells in NSCLC blood was
      significantly higher (P<0.05) compared with normal peripheral blood. The number
      of Foxp3+ T cells was significantly lower (P<0.05) compared with normal
      peripheral blood. The data presented in this study suggest that NSCLC blood
      CD4+CD25high Treg cells are functionally immature and that TGF-beta1 may promote
      maturation.

PMID- 30112068
TI  - Yes-associated protein 1 promotes the metastasis of U251 glioma cells by
      upregulating Jagged-1 expression and activating the Notch signal pathway.
AB  - Yes-associated protein 1 (YAP1) is overexpressed in a number of human cancer
      types as an oncogene and takes part in processes of tumor cell proliferation,
      apoptosis and metastasis. The Notch pathway also has an important role in
      tumorigenesis and progression. However, the possible association between YAP1 and
      Notch signaling in glioma has remained to be determined. The present study
      verified the high expression of YAP1, Jagged 1 (JAG1), NOTCH1 and HES1 in the
      U251 glioma cell line via reverse-transcription quantitative polymerase chain
      reaction and western blot analysis. The effects of YAP1 knockdown with small
      interfering RNA and overexpression of JAG1 or HES1 with the respective
      recombinant plasmid on the expression of these proteins in U251 cells were also
      assessed. The expression of JAG1, intracellular domain of the notch protein and
      HES1 was reduced upon knockdown of YAP1, but the expression of YAP1 was not
      affected by overexpression of JAG1 or HES1. Furthermore, a Transwell assay was
      used to assess the migration of U251 cells in vitro following knockdown of YAP1
      gene and/or overexpression of JAG1 or HES1. U251 cell migration was decreased
      following YAP1 knockdown, which was compensated by overexpression of JAG1 or
      HES1. Overexpression of YAP1 upregulated JAG1 to activate Notch signaling in U251
      cells and YAP1-dependent activity of JAG1, and the Notch pathway promoted the
      metastasis of U251 cells in vitro. This suggested that YAP1 promoted the
      metastasis of U251 cells via upregulating JAG1 and activating Notch signaling.

PMID- 30112069
TI  - Clinical diagnosis and treatment of pediatric anti-N-methyl-D-aspartate receptor
      encephalitis: A single center retrospective study.
AB  - The aim of the present retrospective study was to investigate the diagnosis,
      treatment and prognosis of pediatric anti-N-methyl-D-aspartate receptor (anti
      NMDAR) encephalitis. A total of 23 pediatric patients with anti-NMDAR
      encephalitis were included in the present study. The clinical data, laboratory
      test results, imaging examination, treatment outcomes, and follow-up records were
      reviewed and analyzed. A total of 8 patients exhibited prodromal symptoms,
      including fever, cough, and vomiting. Clinical symptoms included epilepsy,
      convulsions, ataxia, coma, dyskinesia, personal behavior change and
      hallucinations. A total of 20 cases had the initial neurologic symptoms of
      dyskinesia or seizure, whereas 3 cases exhibited psychiatric symptoms of personal
      behavior change and hallucinations. Furthermore, pediatric patients >6 years old
      had more psychiatric symptoms than those <=6 years. A total of 20 cases exhibited
      abnormal electroencephalography records, with 1 case of extreme delta brush. A
      total of 10 cases exhibited abnormal brain magnetic resonance imaging detection.
      Furthermore, the CSF protein contents for pediatric patients <=6 years old was
      significantly higher than those >6 years. For treatment, 18 pediatric patients
      received the first-line treatment of methylprednisone and intravenous injection
      of immunoglobulin, and 6 cases were subjected to the second-line treatment of
      rituximab. A total of 2 patients underwent plasma exchange and/or
      cyclophosphamide treatment. In follow-up, 12 cases reported no convulsion,
      whereas 11 cases had moderate or severe neurological and psychiatric sequelae.
      The recovery rate for pediatric patients <=6 years old was significantly higher
      than those >6 years. Anti-NMDAR encephalitis is commonly seen in pediatric
      patients, mainly with initial neurological symptoms. These patients could respond
      to immunotherapy, and younger pediatric patients typically have a better
      prognosis.

PMID- 30112070
TI  - miR-202 suppresses prostate cancer growth and metastasis by targeting PIK3CA.
AB  - MicroRNA (miR)-202 has been reported to be involved in the regulation of human
      cancer progression including bladder cancer, non-small cell lung cancer,
      pancreatic cancer and esophageal squamous cell carcinoma. However, the function
      of miR-202 in prostate cancer remains largely unknown. The present study
      demonstrated that miR-202 was downregulated in human prostate cancer tissues and
      cell lines. And overexpression of miR-202 significantly inhibited the
      proliferation, migration and invasion of prostate cancer cells, but induced cell
      apoptosis. Moreover, miR-202 suppressed tumor growth in vivo. Regarding the
      underlying mechanism, it was revealed that phosphatidylinositol-4,5-bisphosphate
      3-kinase catalytic subunit alpha (PIK3CA) was a target gene of miR-202 in
      prostate cancer cells. Overexpression of miR-202 inhibited the mRNA and protein
      levels of PIK3CA in prostate cancer cells. Moreover, overexpression of PIK3CA
      abolished the inhibitory effects of miR-202 on prostate cancer cell
      proliferation, migration and invasion in vitro. Taken together, these findings
      demonstrated that miR-202 served as a tumor suppressor in prostate cancer by
      directly targeting PIK3CA.

PMID- 30112071
TI  - Distal myopathy with rimmed vacuoles: Spectrum of GNE gene mutations in seven
      Chinese patients.
AB  - Distal myopathy with rimmed vacuoles (DMRV) is a rare, autosomal, recessive
      inherited disease caused by mutations in the GNE gene. DMRV is an adult-onset
      disorder characterized by progressive muscle atrophy and weakness, which
      initially involves the distal muscles with quadriceps sparing. To date, >150 GNE
      mutations have been reported in different populations from around the world. The
      present study investigated the clinical, pathological and genetic characteristics
      of seven unrelated DMRV patients from China. Genetic analysis in these patients
      revealed three novel mutations (c.455_456insC, p.P421L, and p.A287T) and five
      previously reported mutations (p.D207V, p.C44S, p.G576R, p.A669P, and p.D218G).
      In addition, the literature on DMRV was reviewed to provide an overview of the
      disease and broaden the mutational spectrum of the GNE gene in China.

PMID- 30112072
TI  - Activation of protein kinase C-alpha/heme oxygenase-1 signaling pathway improves
      mitochondrial dynamics in lipopolysaccharide-activated NR8383 cells.
AB  - Mitochondrial function and morphology are dynamically regulated by fusion and
      fission. Heme oxygenase-1 (HO-1), which may be upregulated by protein kinase C
      alpha (PKC-alpha), improves mitochondrial dynamics by controlling the balance
      between fusion and fission in vivo and in vitro. However, whether the PKC
      alpha/HO-1 signaling pathway is one of the underlying mechanisms in adjusting
      mitochondrial dynamics in lipopolysaccharide (LPS)-activated macrophages has
      remained elusive. To explore this, NR8383 cells were pre-treated with PKC-alpha
      inhibitor Go6976 or PKC-alpha activator phorbol-12-myristate-13-acetate for 30
      min and then stimulated with LPS for 24 h. Next, the expression of PKC-alpha, HO
      1, mitofusin 1 (Mfn1) and mitofusin 2 (Mfn2), optic atrophy 1 (OPA1), dynamin
      related protein 1 (Drp1) and fission 1 (Fis1) was detected to evaluate the
      possible implication of the PKC-alpha/HO-1 signaling pathway in the LPS-induced
      NR8383 cells. The results indicated that activation of the PKC-alpha/HO-1
      signaling pathway increased superoxide dismutase activities and the respiratory
      control ratio (RCR), decreased the levels of malondialdehyde, reactive oxygen
      species (ROS), Drp1 and Fis1, and simultaneously enhanced the levels of Mfn1,
      Mfn2 and OPA1. In contrast, the PKC-alpha inhibitor decreased the expression of
      RCR, Mfn1, Mfn2 and OPA1, and increased the expression of MDA and ROS in NR8383
      cells. The results suggest that activation of the PKC-alpha/HO-1 signaling
      pathway is necessary for the balance of mitochondrial dynamics and oxidative
      stress in macrophages, which provides clues for probing novel strategies against
      the detrimental effects of sepsis and other disease states.

PMID- 30112073
TI  - Predictive value of the neutrophil-to-lymphocyte ratio and hemoglobin insystemic
      lupus erythematosus.
AB  - The aim of the present study was to evaluate the association of the neutrophil-to
      lymphocyte ratio (NLR) and hemoglobin levels with disease activity in patients
      with systemic lupus erythematosus (SLE) and to explore their clinical
      significance in predicting SLE. The present study included 212 patients with SLE
      and 201 healthy controls. All the clinical characteristics were collected from
      their medical records. The results revealed that the NLR was elevated and the
      hemoglobin level was markedly decreased in the patients with SLE compared with
      the healthy controls. NLR was positively correlated with the SLE Disease Activity
      Index 2000 (SLEDAI-2K), erythrocyte sedimentation rate (ESR) and C-reactive
      protein (CRP), whereas it was not correlated with C3 or C4. The hemoglobin level
      was negatively correlated with SLEDAI-2K, ESR and CRP and positively correlated
      with C3 and C4. In addition, NLR [EXP(B)=1.986; 95% confidence interval (CI),
      1.432-2.753; P=0.001] and hemoglobin [EXP(B)=0.947; 95% CI, 0.929-0.965; P=0.001]
      were independent predictive factors of SLE. The optimal NLR cut-off value for
      predicting SLE was 2.075, with 71.14% sensitivity and 69.57% specificity, whereas
      the optimal hemoglobin cut-off value was 131.5 mg/l, with 75.79% sensitivity and
      77.98% specificity. In addition, high NLR together with low hemoglobin levels and
      high NLR or low hemoglobin levels had increased positive predictive values (86.05
      and 66.95, respectively). High NLR with low hemoglobin levels and high NLR or low
      hemoglobin levels also had higher sensitivity (64.91 and 92.40, respectively) and
      specificity (64.91 and 18.95, respectively), compared with high NLR alone or low
      hemoglobin alone. In conclusion, NLR and hemoglobin may reflect SLE disease
      activity and may be used as markers for predicting the outcome of SLE.

PMID- 30112075
TI  - TMEM119 silencing inhibits cell viability and causes the apoptosis of gastric
      cancer SGC-7901 cells.
AB  - Gastric cancer is the second major cause of death associated with cancer and
      ranks among the top four cancers diagnosed worldwide. Previous findings
      identified the association of transmembrane proteins (TMEMs) with tumorigenesis
      of various types of cancer, including breast, liver and kidney cancer. However,
      the expression and the biological function of TMEMs, especially TMEM119, and its
      possible molecular mechanism in gastric cancer remain less understood. CCK-8 and
      flow cytometric analysis was employed to examine the viability and apoptosis of
      gastric adenocarcinoma SGC-7901 and AGS cells, gastric carcinoma MKN45 cells, as
      well as gastric epithelial cell lines GES-1 after transfection with TMEM119-siRNA
      (siTMEM119), respectively. Quantitative PCR, western blot analysis and
      immunohistochemistry was performed to detect the expression levels of TMEM119,
      Bax, Bcl-2 and caspase-3. The results showed that, TMEM119 was elevated with the
      highest expression detected in SGC-7901 cells compared to AGS cells, MKN45 cells,
      as well as GES-1. TMEM119 silencing in the gastric cancer cell line, SGC-7901,
      significantly inhibited cell viability and induced apoptosis. The downregulation
      of TMEM119 exhibited reduced levels of Bcl-2 and higher levels of Bax and caspase
      3 in SGC-7901 cells. These results suggest that TMEM119 is useful in the
      treatment of gastric cancer.

PMID- 30112074
TI  - Value of D-dimer levels for the diagnosis of pulmonary embolism: An analysis of
      32 cases with computed tomography pulmonary angiography.
AB  - D-dimer levels correlate with the extent of pulmonary embolism (PE) on computed
      tomography pulmonary angiography (CTPA), but the use of D-dimer alone for
      screening and diagnosing PE remains controversial. This study compared the
      utility of plasma D-dimer levels for diagnosing PE with that of CTPA (gold
      standard). This was a retrospective analysis of 32 consecutive patients with
      suspected PE at the Affiliated Hospital of Yan'an University between OctoberC
      2010 and March 2011. Blood was sampled before thrombolytic therapy was
      administered. D-dimer levels were measured using an automatic system. CTPA was
      used to diagnose PE and was performed within 48 h of blood sampling using a
      Siemens Somatom Sensation 64 computed tomography (CT) scanner. ROC curve analysis
      was performed to evaluate the diagnostic utility of D-dimer levels, with CTPA as
      the gold standard. Among the 32 patients, CTPA identified 26 patients with PE and
      6 patients without obvious abnormality. Using a threshold value of 1.3 ug/ml for
      D-dimer level, the diagnosis of PE was achieved with a sensitivity of 96.2%,
      specificity of 50.0%, positive predictive value of 89.3%, negative predictive
      value of 75.0% and accuracy of 87.5%. D-dimer levels were significantly higher in
      patients positive for PE on CTPA than in those negative for PE on CTPA (9.85+/
      7.14 vs. 2.82+/-2.65 ug/ml, P=0.001). Based on ROC curve analysis, the optimal
      threshold value for D-dimer level in the diagnosis of PE was 1.9 ug/ml. To
      conclude, D-dimer could be a simple, fast and inexpensive screening method for
      excluding a diagnosis of PE.

PMID- 30112076
TI  - Design, synthesis and structure of novel G-2 melamine-based dendrimers
      incorporating 4-(n-octyloxy)aniline as a peripheral unit.
AB  - Background: 4-(n-Octyloxy)aniline is a known component in the elaboration of
      organic materials with mesogenic properties such as N-substituted Schiff bases,
      perylene bisimide assemblies with a number of 2-amino-4,6-bis[4-(n
      octyloxy)phenylamino]-s-triazines, amphiphilic azobenzene-containing linear
      dendritic block copolymers and G-0 monomeric or dimeric dendritic liquid crystals
      with photochromic azobenzene mesogens. The present ab initio study explores a
      previously unknown use of 4-(n-octyloxy)aniline in the synthesis, structure and
      supramolecular behaviour of new dendritic melamines. Results: Starting from 4-(n
      octyloxy)aniline, seven G-2 melamine-based dendrimers were obtained in 29-79%
      overall yields. Their iterative convergent- and chemoselective synthesis
      consisted of SN2-Ar aminations of cyanuric chloride and final triple N-acylations
      and Williamson etherifications (-> G-2 covalent trimers) or stoichiometric
      carboxyl/amino 1:3 neutralisations (-> G-2 ionic trimers). These transformations
      connected G-1 chloro- and amino-termini dendrons to m-trivalent cores (triazin
      2,4,6-triyl and benzene-1,3,5-triyl units) or tripodands (central building
      blocks), such as N-substituted melamines with 4-hydroxyphenyl or phenyl-4
      oxyalkanoic motifs. Owing to the diversity of cores and central building blocks,
      the structural assortment of the dendritic series was disclosed by solvation
      effects (affecting reactivity), rotational stereodynamism and self-organisation
      phenomena (determining a vaulted and/or propeller macromolecular shape in
      solution). DFT calculations (in solution), (VT) NMR and IR (KBr) spectroscopy
      supported these assignments. TEM analysis revealed the ability of the title
      compounds towards self-assembling into homogeneously packed spherical nano
      aggregates. Conclusions: The (non)covalent synthesis and step-by-step structural
      elucidation of novel G-2 melamine dendrimers based on 4-(n-octyloxy)aniline are
      reported. Our study demonstrates the crucial influence of the nature (covalent vs
      ionic) of the dendritic construction in tandem with that of its central building
      blocks on the aptitude of dendrimers to self-organise in solution and to self
      assembly in the solid state.

PMID- 30112078
TI  - Synthesis of pyrimido[1,6-a]quinoxalines via intermolecular trapping of thermally
      generated acyl(quinoxalin-2-yl)ketenes by Schiff bases.
AB  - Acyl(quinoxalin-2-yl)ketenes generated by thermal decarbonylation of 3
      acylpyrrolo[1,2-a]quinoxaline-1,2,4(5H)-triones react regioselectively with
      Schiff bases under solvent-free conditions to form pyrimido[1,6-a]quinoxaline
      derivatives in good yields.

PMID- 30112077
TI  - Host-guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene
      and aromatic N-oxides: solid-state, solution and computational studies.
AB  - Host-guest complexes of C-hexyl-2-bromoresorcinarene (BrC6) with twelve potential
      aromatic N-oxide guests were studied using single crystal X-ray diffraction
      analysis and 1H NMR spectroscopy. In the solid state, of the nine obtained X-ray
      crystal structures, eight were consistent with the formation of BrC6-N-oxide endo
      complexes. The lone exception was from the association between 4-phenylpyridine N
      oxide and BrC6, in that case the host forms a self-inclusion complex. BrC6, as
      opposed to more rigid previously studied C-ethyl-2-bromoresorcinarene and C
      propyl-2-bromoresorcinarene, undergoes remarkable cavity conformational changes
      to host different N-oxide guests through C-H...pi(host) interactions. In solution
      phase CD3OD/CDCl3 (1:1 v/v), all twelve N-oxide guests form endo complexes
      according to 1H NMR; however, in more polar CD3OD/DMSO-d6 (9:1 v/v), only three N
      oxides with electron-donating groups form solution-phase endo complexes with
      BrC6. In solid-state studies, 3-methylpyridine N-oxide+BrC6 crystallises with
      both the upper- and lower-rim BrC6 cavities occupied by N-oxide guests.
      Computational DFT-based studies support that lower-rim long hexyl chains provide
      the additional stability required for this ditopic behaviour. The lower-rim
      cavity, far from being a neutral hydrophobic environment, is a highly polarizable
      electrostatically positive surface, aiding in the binding of polar guests such as
      N-oxides.

PMID- 30112079
TI  - DFT calculations on the mechanism of copper-catalysed tandem arylation
      cyclisation reactions of alkynes and diaryliodonium salts.
AB  - We present a computational mechanistic study on the copper(III)-catalysed
      carboarylation-ring closure reactions leading to the formation of functionalised
      heterocycles. We have performed DFT calculations along selected routes and
      compared their free energy profiles. The calculations considered two viable
      options for the underlying mechanism which differ in the order of the oxazoline
      ring formation and the aryl transfer steps. In our model transformation, it was
      found that the reaction generally features the aryl transfer-ring closing
      sequence and this sequence shows very limited sensitivity to the variation of the
      substituent of the reactants. On the basis of the mechanism the origin of the
      stereoselectivity is ascribed to the interaction of the Cu ion with the oxazoline
      oxygen driving the ring-closure step selectively.

PMID- 30112080
TI  - An amine protecting group deprotectable under nearly neutral oxidative
      conditions.
AB  - The 1,3-dithiane-based dM-Dmoc group was studied for the protection of amino
      groups. Protection was achieved under mild conditions for aliphatic amines, and
      under highly reactive conditions for the less reactive arylamines. Moderate to
      excellent yields were obtained. Deprotection was performed by oxidation followed
      by treating with a weak base. The yields were good to excellent. The new amino
      protecting group offers a different dimension of orthogonality in reference to
      the commonly used amino protecting groups in terms of deprotection conditions. It
      is expected to allow a collection of transformations to be carried out on the
      protected substrates that are unattainable using any known protecting groups.

PMID- 30112082
TI  - Defining the hydrophobic interactions that drive competence stimulating peptide
      (CSP)-ComD binding in Streptococcus pneumoniae.
AB  - Quorum sensing (QS) is a cell-cell communication mechanism that enables bacteria
      to assess their population density and alter their behavior upon reaching high
      cell number. Many bacterial pathogens utilize QS to initiate an attack on their
      host, thus QS has attracted significant attention as a potential antivirulence
      alternative to traditional antibiotics. Streptococcus pneumoniae, a notorious
      human pathogen responsible for a variety of acute and chronic infections,
      utilizes the competence regulon and its associated signaling peptide, the
      competence stimulating peptide (CSP), to acquire antibiotic resistance and
      establish an infection. In this work, we sought to define the binding pockets
      within the ComD1 receptor used for binding the hydrophobic side-chain residues in
      CSP1 through the introduction of highly-conservative point mutations within the
      peptide. Optimization of these binding interactions could lead to the development
      of highly potent CSP-based QS modulators while the inclusion of non-natural amino
      acids within the CSP sequence would confer resistance to protease degradation, a
      requirement for drug candidates.

PMID- 30112081
TI  - Synthesis and photophysical studies of a multivalent photoreactive RuII
      calix[4]arene complex bearing RGD-containing cyclopentapeptides.
AB  - Photoactive ruthenium-based complexes are actively studied for their biological
      applications as potential theragnostic agents against cancer. One major issue of
      these inorganic complexes is to penetrate inside cells in order to fulfil their
      function, either sensing the internal cell environment or exert a photocytotoxic
      activity. The use of lipophilic ligands allows the corresponding ruthenium
      complexes to passively diffuse inside cells but limits their structural and
      photophysical properties. Moreover, this strategy does not provide any cell
      selectivity. This limitation is also faced by complexes anchored on cell
      penetrating peptides. In order to provide a selective cell targeting, we
      developed a multivalent system composed of a photoreactive ruthenium(II) complex
      tethered to a calix[4]arene platform bearing multiple RGD-containing
      cyclopentapeptides. Extensive photophysical and photochemical characterizations
      of this Ru(II)-calixarene conjugate as well as the study of its photoreactivity
      in the presence of guanosine monophosphate have been achieved. The results show
      that the ruthenium complex should be able to perform efficiently its photoinduced
      cytotoxic activity, once incorporated into targeted cancer cells thanks to the
      multivalent platform.

PMID- 30112084
TI  - Graphitic carbon nitride prepared from urea as a photocatalyst for visible-light
      carbon dioxide reduction with the aid of a mononuclear ruthenium(II) complex.
AB  - Graphitic carbon nitride (g-C3N4) was synthesized by heating urea at different
      temperatures (773-923 K) in air, and was examined as a photocatalyst for CO2
      reduction. With increasing synthesis temperature, the conversion of urea into g
      C3N4 was facilitated, as confirmed by X-ray diffraction, FTIR spectroscopy and
      elemental analysis. The as-synthesized g-C3N4 samples, further modified with Ag
      nanoparticles, were capable of reducing CO2 into formate under visible light
      (lambda > 400 nm) in the presence of triethanolamine as an electron donor, with
      the aid of a molecular Ru(II) cocatalyst (RuP). The CO2 reduction activity was
      improved by increasing the synthesis temperature of g-C3N4, with the maximum
      activity obtained at 873-923 K. This trend was also consistent with that observed
      in photocatalytic H2 evolution using Pt-loaded g-C3N4. The photocatalytic
      activities of RuP/g-C3N4 for CO2 reduction and H2 evolution were thus shown to be
      strongly associated with the generation of the crystallized g-C3N4 phase.

PMID- 30112083
TI  - Synthesis of spirocyclic scaffolds using hypervalent iodine reagents.
AB  - Hypervalent iodine reagents have been developed as highly valuable reagents in
      synthetic organic chemistry during the past few decades. These reagents have been
      identified as key replacements of various toxic heavy metals in organic
      synthesis. Various synthetically and biologically important scaffolds have been
      developed using hypervalent iodine reagents either in stoichiometric or catalytic
      amounts. In addition, hypervalent iodine reagents have been employed for the
      synthesis of spirocyclic scaffolds via dearomatization processes. In this review,
      various approaches for the synthesis of spirocyclic scaffolds using hypervalent
      iodine reagents are covered including their stereoselective synthesis.
      Additionally, the applications of these reagents in natural product synthesis are
      also covered.

PMID- 30112086
TI  - Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5
      d][1,4]diazepine derivatives by [3+ + 2]-cycloaddition/rearrangement reactions.
AB  - Two new series of tricyclic heterocycles, namely 5,6-dihydro-4H
      benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepinium salts 10 and the related neutral,
      free bases 13 were synthesized from 4-acetoxy-1-acetyl-4-phenylazo-1,2,3,4
      tetrahydroquinolines 8 and nitriles 9 in the presence of aluminium chloride by
      the [3+ + 2]-cycloaddition reaction of the in situ generated azocarbenium
      intermediates 14 followed by a ring-expansion rearrangement. In the rearrangement
      reaction, the phenyl substituent in the initially formed spiro-triazolium adducts
      16 underwent a [1,2]-migration from C(3) to the electron-deficient N(2). This led
      to the ring expansion from 6-membered piperidine to 7-membered diazepine
      furnishing the tricyclic 1,2,4-triazole-fused 1,4-benzodiazepines.

PMID- 30112087
TI  - First thia-Diels-Alder reactions of thiochalcones with 1,4-quinones.
AB  - Aryl and hetaryl thiochalcones react smoothly with 1,4-quinones in THF solution
      at 60  degrees C yielding the corresponding fused 4H-thiopyrans after spontaneous
      dehydrogenation of the initially formed [4 + 2] cycloadducts. In general, the
      yields of the isolated products were high. With 5-chloro-10-hydroxy-1,4
      anthraquinone, the thia-Diels-Alder reaction occurred with complete
      regioselectivity. In the case of the reaction of vitamin K3 (menadione) with
      diphenylthiochalcone, the initial cycloadduct was isolated in 37% yield.

PMID- 30112085
TI  - Recent advances in hypervalent iodine(III)-catalyzed functionalization of
      alkenes.
AB  - Hypervalent iodine(III) reagents have been well-developed and widely utilized in
      functionalization of alkenes, however, generally either stoichiometric amounts of
      iodine(III) reagents are required or stoichiometric oxidants such as mCPBA are
      employed to in situ generate iodine(III) species. In this review, recent
      developments of hypervalent iodine(III)-catalyzed functionalization of alkenes
      and asymmetric reactions using a chiral iodoarene are summarized.

PMID- 30112088
TI  - Strong binding and fluorescence sensing of bisphosphonates by guanidinium
      modified calix[5]arene.
AB  - Based on the indicator displacement assay (IDA) approach, we herein report the
      fluorescence "switch-on" sensing and quantitative detection of bisphosphonates
      (BPs), a class of drugs extensively used in the treatment of patients with
      various skeletal diseases. Guanidinium-modified calix[5]arene (GC5A) affords
      strong binding on the micromolar to nanomolar level towards BPs dominantly via
      multiple salt bridge interactions, which was evaluated by fluorescence
      competitive titrations. Fluorescent IDA enables the highly sensitive and label
      free detection of BPs in buffer solution, and more importantly, in artificial
      urine. Calibration lines were therefore set up in untreated artificial urine,
      allowing for quantifying the concentrations of BPs in the biologically relevant
      low range.

PMID- 30112089
TI  - Efficient catenane synthesis by cucurbit[6]uril-mediated azide-alkyne
      cycloaddition.
AB  - We report here the efficient synthesis of a series of [3]catenanes featuring the
      use of cucurbit[6]uril to simultaneously mediate the mechanical and covalent bond
      formations. By coupling the mechanical interlocking with covalent
      macrocyclization, formation of topological isomers is eliminated and the
      [3]catenanes are formed exclusively in good yields. The efficient access to these
      [3]catenanes and the presence of other recognition units render them promising
      building blocks for the construction of other high-order interlocked structures.

PMID- 30112090
TI  - Preparation and X-ray structure of 2-iodoxybenzenesulfonic acid (IBS) - a
      powerful hypervalent iodine(V) oxidant.
AB  - The selective preparation of 2-iodoxybenzenesulfonic acid (IBS, as potassium or
      sodium salts) by oxidation of sodium 2-iodobenzenesulfonate with Oxone or sodium
      periodate in water is reported. The single crystal X-ray diffraction analysis
      reveals a complex polymeric structure consisting of three units of IBS as
      potassium salt and one unit of 2-iodoxybenzenesulfonic acid linked together by
      relatively strong I=O...I intermolecular interactions. Furthermore, a new method
      for the preparation of the reduced form of IBS, 2-iodosylbenzenesulfonic acid, by
      using periodic acid as an oxidant, has been developed. It has been demonstrated
      that the oxidation of free 2-iodobenzenesulfonic acid under acidic conditions
      affords an iodine(III) heterocycle (2-iodosylbenzenesulfonic acid), while the
      oxidation of sodium 2-iodobenzenesulfonate in neutral aqueous solution gives the
      iodine(V) products.

PMID- 30112091
TI  - Water-soluble SNS cationic palladium(II) complexes and their Suzuki-Miyaura cross
      coupling reactions in aqueous medium.
AB  - Unlike their SCS analogues, SNS pincer complexes are poorly studied for their use
      in coupling reactions. Accordingly, a series of water soluble cationic Pd(II) SNS
      pincer complexes have been successfully synthesised and investigated in detail
      for their catalytic activity in Suzuki-Miyaura coupling reactions. By using only
      0.5 mol % loading of the complexes, the coupling of inactivated aryl bromides and
      activated aryl chlorides with various boronic acids in water was achieved in
      excellent yields and the catalysts were found to be reusable for three cycles
      without a significant loss of activity. The investigation of the mechanism of the
      reaction revealed that a Pd(II) to Pd(IV) route is the more likely pathway which
      was further supported by computational studies.

PMID- 30112092
TI  - Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium
      derivatives by Palladium-mediated cross-coupling reactions.
AB  - 9-Arylbenzo[b]quinolizinium derivatives were prepared with base-free Suzuki
      Miyaura coupling reactions between benzo[b]quinolizinium-9-trifluoroborate and
      selected benzenediazonium salts. In addition, the Sonogashira coupling reaction
      between 9-iodobenzo[b]quinolizinium and the arylalkyne derivatives yielded four
      novel 9-(arylethynyl)benzo[b]quinolizinium derivatives under relatively mild
      reaction conditions. The 9-(N,N-dimethylaminophenylethynyl)benzo[b]quinolizinium
      is only very weakly emitting, but the emission intensity increases by a factor
      >200 upon protonation, so that this derivative may operate as pH-sensitive light
      up probe. Photometric and fluorimetric titrations of duplex and quadruplex DNA to
      9-(arylethynyl)benzo[b]quinolizinium derivatives revealed a significant binding
      affinity of these compounds towards both DNA forms with binding constants of Kb =
      0.2-2.2 * 105 M-1.

PMID- 30112093
TI  - A hemicryptophane with a triple-stranded helical structure.
AB  - A hemicryptophane cage bearing amine and amide functions in its three linkers was
      synthesized in five steps. The X-ray molecular structure of the cage shows a
      triple-stranded helical arrangement of the linkers stabilized by intramolecular
      hydrogen bonds between amide and amine groups. The chirality of the
      cyclotriveratrylene unit controls the propeller arrangement of the three aromatic
      rings in the opposite part of the cage. 1H NMR studies suggest that this
      structure is retained in solution.

PMID- 30112095
TI  - Asymmetric Michael addition reactions catalyzed by calix[4]thiourea
      cyclohexanediamine derivatives.
AB  - A number of upper rim-functionalized calix[4]thiourea cyclohexanediamine
      derivatives have been designed, synthesized and used as catalysts for
      enantioselective Michael addition reactions between nitroolefins and
      acetylacetone. The optimal catalyst 2 with a mono-thiourea group exhibited good
      performance in the presence of water/toluene (v/v = 1:2). Under the optimal
      reaction conditions, high yields of up to 99% and moderate to good
      enantioselectivities up to 94% ee were achieved. Detailed experiments clearly
      showed that the upper rim-functionalized hydrophobic calixarene scaffold played
      an important role in cooperation with the catalytic center to the good
      reactivities and enantioselectivities.

PMID- 30112094
TI  - Diazirine-functionalized mannosides for photoaffinity labeling: trouble with
      FimH.
AB  - Photoaffinity labeling is frequently employed for the investigation of ligand
      receptor interactions in solution. We have employed an interdisciplinary
      methodology to achieve facile photolabeling of the lectin FimH, which is a
      bacterial protein, crucial for adhesion, colonization and infection. Following
      our earlier work, we have here designed and synthesized diazirine-functionalized
      mannosides as high-affinity FimH ligands and performed an extensive study on
      photo-crosslinking of the best ligand (mannoside 3) with a series of model
      peptides and FimH. Notably, we have employed high-performance mass spectrometry
      to be able to detect radiation results with the highest possible accuracy. We are
      concluding from this study that photolabeling of FimH with sugar diazirines has
      only very limited success and cannot be regarded a facile approach for covalent
      modification of FimH.

PMID- 30112096
TI  - A pyridinium/anilinium [2]catenane that operates as an acid-base driven optical
      switch.
AB  - A two-station [2]catenane containing a large macrocycle with two different
      recognition sites, one bis(pyridinium)ethane and one benzylanilinium, as well as
      a smaller DB24C8 ring was synthesized and characterized. 1H NMR spectroscopy
      showed that the DB24C8 ring can shuttle between the two recognition sites
      depending on the protonation state of the larger macrocycle. When the aniline
      group is neutral, the DB24C8 ring resides solely at the bis(pyridinium)ethane
      site, while addition of acid forms a charged benzylanilinium site. The DB24C8
      then shuttles between the two charged recognition sites with occupancy favoring
      the bis(pyridinium)ethane site by a ratio of 4:1. The unprotonated [2]catenane
      has a deep yellow/orange color when the DB24C8 ring resides solely at the
      bis(pyridinium)ethane site and changes to colorless when the crown ether is
      shuttling (i.e., circumrotating) back and forth between the two recognition sites
      thus optically signalling the onset of the shuttling dynamics.

PMID- 30112098
TI  - An amphiphilic pseudo[1]catenane: neutral guest-induced clouding point change.
AB  - The hydrophobic/hydrophilic ratio in a molecule largely affects its assembled
      properties in aqueous media. In this study, we synthesized a new bicyclic
      compound which could dynamically change its hydrophobic/hydrophilic ratio by
      chemical stimulus. The bicyclic compound consisted of amphiphilic pillar[5]arene
      and hydrophobic alkyl chain rings, and formed a self-inclusion structure in
      aqueous media, which was assigned as a pseudo[1]catenane structure. The
      hydrophobic chain ring was hidden inside the pillar[5]arene cavity in the
      pseudo[1]catenane structure, thus the bicyclic compound was soluble in water at
      20  degrees C with a clouding point at 24  degrees C. The pseudo[1]catenane was
      converted to the de-threaded structure upon addition of the neutral guest 1,4
      dicyanobutane, which displaced the alkyl chain ring from the inside to the
      outside of the cavity. The hydrophobic alkyl chain ring was now exposed to the
      aqueous media, causing aggregation of the hydrophobic alkyl chain rings, which
      induced insolubilization of the bicyclic compound in aqueous media at 20  degrees
      C and a decrease in its clouding point.

PMID- 30112099
TI  - Recent advances in materials for organic light emitting diodes.

PMID- 30112097
TI  - Assessing the possibilities of designing a unified multistep continuous flow
      synthesis platform.
AB  - The multistep flow synthesis of complex molecules has gained momentum over the
      last few years. A wide range of reaction types and conditions have been
      integrated seamlessly on a single platform including in-line separation as well
      as monitoring. Beyond merely getting considered as 'flow version' of conventional
      'one-pot synthesis', multistep flow synthesis has become the next generation tool
      for creating libraries of new molecules. Here we give a more 'engineering' look
      at the possibility of developing a 'unified multistep flow synthesis platform'. A
      detailed analysis of various scenarios is presented considering 4 different
      classes of drugs already reported in the literature. The possible complexities
      that an automated and controlled platform needs to handle are also discussed in
      detail. Three different design approaches are proposed: (i) one molecule at a
      time, (ii) many molecules at a time and (iii) cybernetic approach. Each approach
      would lead to the effortless integration of different synthesis stages and also
      at different synthesis scales. While one may expect such a platform to operate
      like a 'driverless car' or a 'robo chemist' or a 'transformer', in reality, such
      an envisaged system would be much more complex than these examples.

PMID- 30112101
TI  - Keeping the Flow Going: FGFR1 Protects Vascular Patency by Inhibiting Occlusive
      Neointimal Hyperplasia.

PMID- 30112100
TI  - Artificial bioconjugates with naturally occurring linkages: the use of
      phosphodiester.
AB  - Artificial orthogonal bond formations such as the alkyne-azide cycloaddition have
      enabled selective bioconjugations under mild conditions, yet naturally occurring
      linkages between native functional groups would be more straightforward to
      elaborate bioconjugates. Herein, we describe the use of a phosphodiester bond as
      a versatile option to access various bioconjugates. An opposite activation
      strategy, involving 5'-phosphitylation of the supported oligonucleotides, has
      allowed several biomolecules that possess an unactivated alcohol to be directly
      conjugated. It should be noted that there is no need to pre-install artificial
      functional groups and undesired and unpredictable perturbations possibly caused
      by bioconjugation can be minimized.

PMID- 30112102
TI  - Etidronate prevents, but does not reverse, ectopic mineralization in a mouse
      model of pseudoxanthoma elasticum (Abcc6-/- ).
AB  - Pseudoxanthoma elasticum (PXE) and generalized arterial calcification of infancy
      (GACI) are heritable disorders manifesting with ectopic tissue mineralization.
      Most cases of PXE and some cases of GACI are caused by mutations in the ABCC6
      gene, resulting in reduced plasma pyrophosphate (PPi) levels. There is no
      effective treatment for these disorders. It has been suggested that
      administration of bisphosphonates, stable and non-hydrolyzable PPi analogs, could
      counteract ectopic mineralization in these disorders. In this study we tested the
      potential efficacy of etidronate, a first generation bisphosphonate, on ectopic
      mineralization in the muzzle skin of Abcc6-/- mice, a model of PXE. The Abcc6-/-
      mice received subcutaneous injections of etidronate, 0.283 and 3.40 mg/kg per
      injection (0.01* and 0.12*), twice a week, in both prevention and reversal
      studies. Ectopic mineralization in the dermal sheath of vibrissae in muzzle skin
      was determined by histopathologic analysis and by direct chemical assay for
      calcium content. Subcutaneous injection of etidronate prevented ectopic
      mineralization but did not reverse existing mineralization. The effect of
      etidronate was accompanied by alterations in the trabecular bone
      microarchitecture, determined by micro-computed tomography. The results suggest
      that etidronate may offer a potential treatment modality for PXE and GACI caused
      by ABCC6 mutations. Etidronate therapy should be initiated in PXE patients as
      soon as the diagnosis is made, with careful monitoring of potential side effects.

PMID- 30112103
TI  - Systematic verification of bladder cancer-associated tissue protein biomarker
      candidates in clinical urine specimens.
AB  - Bladder cancer biomarkers currently approved by the Food and Drug Administration
      are insufficiently reliable for use in non-invasive clinical diagnosis.
      Verification/validation of numerous biomarker candidates for BC detection is a
      crucial bottleneck for novel biomarker development. A multiplexed liquid
      chromatography multiple-reaction-monitoring mass spectrometry assay of 122
      proteins, including 118 up-regulated tissue proteins, two known bladder cancer
      biomarkers and two housekeeping gene products, was successfully established for
      protein quantification in clinical urine specimens. Quantification of 122
      proteins was performed on a large cohort of urine specimens representing a
      variety of conditions, including 142 hernia, 126 bladder cancer, 67 hematuria,
      and 59 urinary tract infection samples. ANXA3 (annexin A3) and HSPE1 (heat shock
      protein family E member 1), which showed the highest detection frequency in
      bladder cancer samples, were selected for further validation. Western blotting
      showed that urinary ANXA3 and HSPE1 protein levels were higher in bladder cancer
      samples than in hernia samples, and enzyme-linked immunosorbent assays confirmed
      a higher urinary concentration of HSPE1 in bladder cancer than in hernia,
      hematuria and urinary tract infection. Immunohistochemical analyses showed
      significantly elevated levels of HSPE1 in tumor cells compared with non-cancerous
      bladder epithelial cells, suggesting that HSPE1 could be a useful tumor tissue
      marker for the specific detection of bladder cancer. Collectively, our findings
      provide valuable information for future validation of potential biomarkers for
      bladder cancer diagnosis.

PMID- 30112104
TI  - PM2.5 induced cardiac hypertrophy via CREB/GSK3b/SOS1 pathway and metabolomics
      alterations.
AB  - The particle matter with diameter less 2.5MUm (PM2.5) easier to adsorb toxic
      substance, and interfere with pulmonary gas exchange. In this study,
      cardioprotective effects of low molecular weight (LMW) fucoidan in cardiac
      hypertrophy subjects induced by PM2.5 exposure was conducted by measuring QT
      interval, Blood pressure, cardiac structure, metabolites and proteins expression
      in different organs. After PM2.5 exposure, increase in blood pressure, abnormal
      cardiac function (Prolongation of Action Potential Duration and QT Interval), and
      structral remodeling (cardiac hypertrophy and fibrosis) were recorded. Fucoidan
      supplement in consecutive 28 days can reduce the damage to myocardial injury
      caused by PM2.5. Clearance effect of fucoidan in serum, heart, kidney, lung and
      liver was found due to organic and inorganic compounds reduced SOS1, CREB, GSK3b,
      and GRB2 protein level were changed under PM2.5 exposure. Whereas, only CREB
      level was reduced after fucoidan treatment. Metabolic alteration was also
      determined that PM2.5 severely damage cardiac tissue and compromise its function.
      After treatment with fucoidan, the cardiac function was significantly recovered.
      Our finding demonstrated that LMW could enhance the cardiac status of mice with
      PM2.5 exposures by rescued QT interval prolongation, action potential and cardiac
      hypertrophy, and cardiac fibrosis decline.

PMID- 30112105
TI  - NGAL promotes recruitment of tumor infiltrating leukocytes.
AB  - We have previously shown that Neutrophil Gelatinase-Associated Lipocalin (NGAL)
      is strongly expressed in thyroid carcinomas, especially of anaplastic type, where
      it protects neoplastic cells from serum deprivation-induced apoptosis and
      enhances tumor invasivity by regulating MMP-9 activity. Here we demonstrate that
      NGAL-containing conditioned medium from human anaplastic thyroid carcinoma (ATC)
      cells is able to induce monocyte migration via up-regulation of a number of
      different chemokines. The enhanced chemokines transcription is due to the NGAL
      mediated intracellular iron uptake. Very importantly, mice tumor allografts
      raised from subcutaneous injection of syngeneic colon carcinoma cell lines,
      expressing high levels of NGAL, show a dense leukocyte infiltrate which strongly
      decreases in tumor allografts from NGAL-depleted cell injected mice. Our results
      indicate that the NGAL promotes leukocytes recruitment in tumor microenvironment
      through iron-mediated chemokines production.

PMID- 30112106
TI  - Selinexor reduces the expression of DNA damage repair proteins and sensitizes
      cancer cells to DNA damaging agents.
AB  - Introduction: The goal of this study was to examine the effects of selinexor, an
      inhibitor of exportin-1 mediated nuclear export, on DNA damage repair and to
      evaluate the cytotoxic effects of selinexor in combination with DNA damaging
      agents (DDAs) in cancer cells. Results: Selinexor reduced the expression of DNA
      damage repair (DDR) proteins. This did not induce significant DNA damage in
      tested cell lines. Inhibition of DDR protein expression resulted in enhanced
      cancer cell death when cells were pretreated with DDAs. In contrast, enhanced
      cell death was not detected in cells that were pretreated with selinexor then
      with DDAs. In vivo, single-agent selinexor, docetaxel, or cisplatin treatment
      resulted in 66.7%, 51.5%, and 26.6% tumor growth inhibition (TGI), respectively,
      in an MDA-MB-231 xenograft model. Consequently, combination treatment with
      docetaxel or cisplatin followed by selinexor in vivo resulted in 93.9% and 103.4%
      TGI, respectively. Immunohistochemical staining and immunoblot analysis of tumor
      sections confirmed reduced expression of DDR proteins. Conclusion: Selinexor
      treatment inhibited DDR mechanisms in cancer cell lines and therefore potentiated
      DNA damage-based therapy. The sequential combination of DDAs followed by
      selinexor increased cancer cell death. This combination is superior to each
      individual therapy and has a mechanistic rationale as a novel anticancer
      strategy. Methods: Cancer cells treated with selinexor +/- DDAs were analyzed
      using reverse phase protein arrays, immunoblots, quantitative PCR and
      immunofluorescence. Mice bearing MDA-MB-231 tumors were treated with
      subtherapeutic doses of selinexor, cisplatin, docetaxel and selinexor in
      combination with either cisplatin or docetaxel. Tumor growth was evaluated for 25
      days.

PMID- 30112108
TI  - Mebendazole stimulates CD14+ myeloid cells to enhance T-cell activation and
      tumour cell killing.
AB  - Mebendazole (MBZ) was recently shown to induce a tumor suppressive M1 phenotype
      in THP-1 monocytes and macrophages. In the present study the immune effects of
      MBZ was further investigated using human peripheral blood mononuclear cells
      (PBMCs) co-cultured with tumour cells. The Biomap platform was used to screen for
      biomarkers induced from MBZ exposed co-cultures of T-cell receptor activated
      PBMCs, HT29 colon cancer cells and either human fibroblasts or human umbilical
      vein endothelial cells (HUVEC) cells. In these co-culture systems MBZ at 0.3-10
      MUM induced significant increases in TNFalpha and IFNgamma indicating immune
      stimulation. PBMC cultures alone were subsequently tested for activation status
      and only in PBMCs activated by CD3/IL2 stimulation and MBZ, at a clinically
      achievable concentration, was able to increase PBMC clustering and release of pro
      inflammatory IFNgamma, TNFalpha, IL6 and IL1beta cytokines. Moreover, when PBMC
      cultures were functionally tested for immune cell killing of lung cancer
      A549NucLightRed cells, MBZ significantly increased tumour cell apoptosis and
      reduced the number of surviving tumour cells. This effect was dependent on the
      presence of CD14 monocytes/macrophages in the co-culture. In summary, MBZ
      potentiated the immune stimulatory and anticancer effects of anti-CD3/IL2
      activated PBMCs which could be relevant to explain the anticancer activity of MBZ
      observed in the clinic.

PMID- 30112109
TI  - Cell based functional assays for IDO1 inhibitor screening and characterization.
AB  - Indoleamine 2,3-dioxygenase 1 (IDO1) is a new immune-oncology target and its
      inhibitors have shown promise in the clinic especially in combination with other
      immune-stimulating agents. Here we describe two robust cell-based assays for
      screening IDO1 inhibitors. Both assays can be easily adopted by most laboratories
      and utilized for screening of IDO1 inhibitors. Endogenous IDO1 expression is
      induced in a cancer cell line with interferon gamma and its activity is assessed
      by measuring kynurenine secreted into the media. The effect of cancer cell IDO1
      induction and inhibition on T cell activation is evaluated in a co-culture assay
      using Jurkat T cell line. Additional readouts assessing cell viability are
      employed for early detection of false positive IDO1 inhibitors and toxic
      compounds. Clinical candidates epacadostat and BMS-986205 were evaluated in the
      assays as control compounds, the former can completely inhibit IDO1 activity
      while the maximum effect of the later is limited (to about 80% in our system)
      consistent with the differences in their interaction with IDO1. Nanomolar
      concentrations of both compounds rescued IDO1 mediated inhibition of T cell
      activation. However, treatment with micromolar concentrations of BMS-986205
      blocked Jurkat T cell activation and after prolonged incubation induced cell
      death.

PMID- 30112107
TI  - Autophagy-dependent apoptosis is triggered by a semi-synthetic [6]-gingerol
      analogue in triple negative breast cancer cells.
AB  - Triple negative breast cancer (TNBC) is very aggressive and lacks specific
      therapeutic targets, having limited treatment options and poor prognosis. [6]
      gingerol is the most abundant and studied compound in ginger, presenting diverse
      biological properties such as antitumor activity against several types of cancer,
      including breast cancer. In this study, we show that the semi-synthetic analogue
      SSi6, generated after chemical modification of the [6]-gingerol molecule, using
      acetone-2,4-dinitrophenylhydrazone (2,4-DNPH) reagent, enhanced selective
      cytotoxic effects on MDA-MB-231 cells. Remarkably, unlike the original [6]
      gingerol molecule, SSi6 enabled autophagy followed by caspase-independent
      apoptosis in tumor cells. We found a time-dependent association between SSi6
      induced oxidative stress, autophagy and apoptosis. Initial SSi6-induced reactive
      oxygen species (ROS) accumulation (1h) led to autophagy activation (2-6h), which
      was followed by caspase-independent apoptosis (14h) in TNBC cells. Additionally,
      our data showed that SSi6 induction of ROS plays a key role in the promotion of
      autophagy and apoptosis. In order to investigate whether the observed cell death
      induction was dependent on preceding autophagy in MDA-MB-231 cells, we used siRNA
      to knock down LC3B prior to SSi6 treatment. Our data show that LC3B
      downregulation decreased the number of apoptotic cells after treatment with SSi6,
      indicating that autophagy is a key initial step on SSi6-induced caspase
      independent apoptosis. Overall, the results of this study show that structural
      modifications of natural compounds can be an interesting strategy for developing
      antitumor drugs, with distinct mechanisms of actions, which could possibly be
      used against triple negative breast cancer cells that are resistant to canonical
      apoptosis-inducing drugs.

PMID- 30112110
TI  - Silencing of casein kinase 1 delta reduces migration and metastasis of triple
      negative breast cancer cells.
AB  - The casein kinase 1 delta (CSNK1D) is a conserved serine/threonine protein kinase
      that regulates diverse cellular processes including cell cycle progression,
      circadian rhythm, and neurite outgrowth. Aberrant expression of CSNK1D is
      described in several cancer types including breast cancer, where it is amplified
      in about 30% of triple negative breast (TNBC). Here, we have investigated the
      function of CSNK1D in triple negative cancer cell migration and metastasis. By
      using immunohistochemistry and in situ hybridization, we found that CNSK1D is
      highly expressed in primary tumor cells and in tumor cells invading lymphatic
      nodes compared to non-metastatic tumors. In vitro, knock-down of CSNK1D
      expression with specific shRNAs in the breast cancer cell line MDA-MB-231
      markedly inhibited cancer cell proliferation, invasion and migration and affected
      the expression of the tight junction proteins claudin 1, occludin and the
      junction adhesion molecule A. In vivo, the inactivation of CSNK1D reduced lung
      metastasis in MDA-MB-231 breast cancer xenografts. Altogether, our results
      indicate that the downregulation of CSNK1D expression inhibits the proliferation
      and reduces the migration and the metastasis of breast cancer cells. As numerous
      inhibitors of CSNK1D are currently under development, this might represent an
      attractive therapeutic target for the treatment of TNBC.

PMID- 30112111
TI  - Chloroquine plays a cell-dependent role in the response to treatment of
      pancreatic adenocarcinoma.
AB  - In this study, our aim is to assess the role played by autophagy and its
      inhibition in the different PDAC cellular compartments, and its involvement in
      chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and
      Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II
      in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found
      no correlation between autophagy level and degree of tumor differentiation.
      Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and
      docetaxel revealed that its effect on survival is cell- and drug-dependent in
      vitro and in vivo. In addition, we demonstrated that autophagy in CAFs can play
      an important role in sensitizing PDAC to anticancer treatments since its
      inhibition increased the resistance of PCCs to gemcitabine. In conclusion, this
      work clearly shows a heterogeneity in the effect of Chloroquine and highlights a
      role of CAFs autophagy in sensitizing tumors to treatments. It also reveals that
      the role of autophagy is more complex than expected in PDAC as well as its
      sensitivity to treatments.

PMID- 30112112
TI  - Intratumoral immune-biomarkers and mismatch repair status in leiyomyosarcoma 
      potential predictive markers for adjuvant treatment: a pilot study.
AB  - Leiomyosarcoma is the second most frequent soft-tissue sarcoma. Tumor lymphocytic
      infiltration (TIL) and programed cell death ligand-1 (PD-L1) have been associated
      with prognosis in different malignancies while DNA mismatch-repair deficiency
      (MMR-D) has been associated with response to check-point inhibitors. In this
      pilot study, we sought to examine TIL, PD-L1 and mismatch-repair (MMR) protein
      expression in 11 leiomyosarcoma and its association with outcome as potential
      biomarkers for adjuvant treatment. Eleven primary leiomyosarcoma archived-tissues
      were analyzed for expression of MMR proteins (MSH2, MLH1, MSH6 and PSM2), PD-L1
      expression and PD-1, CD3 or CD8. MMR-D was detected in tumor tissue from 2/11
      leiomyosarcoma patients. CD3 T-cells were present in all samples, whereas CD8
      staining was positive in all but one. PDL-1 was positive in 4/11 and PD-L1 in
      6/11. Interestingly, the three patients with the poorest outcome had strongly
      positive staining for PD-L1 and CD8 while in the two patients who are alive and
      recurrence-free, both PD-L1 and CD8 infiltration were lacking. We found an
      association between tumor infiltrating CD8 cytotoxic lymphocytes, strong PD-L1
      staining and survival; suggesting a role as biomarkers for treatment decisions
      regarding peri-operative chemotherapy. We also identified MMR-D in two patients
      with leiomyosarcoma comprising 18% of our sample.

PMID- 30112113
TI  - Influence of age on radiomic features in 18F-FDG PET in normal breast tissue and
      in breast cancer tumors.
AB  - Background: To help interpret measurements in breast tissue and breast tumors
      from 18F-FDG PET scans, we studied the influence of age in measurements of PET
      parameters in normal breast tissue and in a breast cancer (BC) population.
      Results: 522 women were included: 331 pts without history of BC (B-VOI) and 191
      patients with BC (T-VOI). In B-VOI, there were significant differences between
      all age groups for Standardized Uptake Values (SUVs) and for 12 textural indices
      (TI) whereas histogram-based indices (HBI) did not vary between age groups. SUV
      values decreased over time whereas Homogeneity increased. We had a total of 210 T
      VOI and no significant differences were found according to the histological type
      between 190 ductal carcinoma and 18 lobular carcinoma. Conversely, according to
      BC subtype most differences in PET parameters between age groups were found in
      Triple-Negative tumors (52) for 9 TI. On post-hoc Hochberg, most differences were
      found between the <45 year old (PRE) group and POST groups in NBT and in Triple
      Negative tumors. Conclusion: We found significant SUVs and TI differences as a
      function of age in normal breast tissue and in BC radiomic phenotype with Triple
      Negative tumors being the most affected. Our findings suggest that age should be
      taken into account as a co-covariable in radiomic models. Methods: Patients were
      classified in 3 age groups: <45 yo (PRE), >=45 and <55 yo (PERI) and >=55 and <85
      yo (POST) and we compared PET parameters using Anova test with post-hoc
      Bonferroni/Hochberg analyses: SUV (max, mean and peak), HBI and TI in both
      breasts and in breast tumor regions.

PMID- 30112114
TI  - Applied diagnostics in liver cancer. Efficient combinations of sorafenib with
      targeted inhibitors blocking AKT/mTOR.
AB  - Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related
      deaths worldwide. There is increasing interest in developing specific markers to
      serve as predictors of response to sorafenib and to guide targeted therapy. Using
      a sequencing platform designed to study somatic mutations in a selection of 112
      genes (HepatoExome), we aimed to characterize lesions from HCC patients and cell
      lines, and to use the data to study the biological and mechanistic effects of
      case-specific targeted therapies used alone or in combination with sorafenib. We
      characterized 331 HCC cases in silico and 32 paired samples obtained
      prospectively from primary tumors of HCC patients. Each case was analyzed in a
      time compatible with the requirements of the clinic (within 15 days). In 53% of
      the discovery cohort cases, we detected unique mutational signatures, with up to
      34% of them carrying mutated genes with the potential to guide therapy. In a
      panel of HCC cell lines, each characterized by a specific mutational signature,
      sorafenib elicited heterogeneous mechanistic and biological responses, whereas
      targeted therapy provoked the robust inhibition of cell proliferation and DNA
      synthesis along with the blockage of AKT/mTOR signaling. The combination of
      sorafenib with targeted therapies exhibited synergistic anti-HCC biological
      activity concomitantly with highly effective inhibition of MAPK and AKT/mTOR
      signaling. Thus, somatic mutations may lead to identify case-specific mechanisms
      of disease in HCC lesions arising from multiple etiologies. Moreover, targeted
      therapies guided by molecular characterization, used alone or in combination with
      sorafenib, can effectively block important HCC disease mechanisms.

PMID- 30112115
TI  - Association between genetic polymorphisms and platinum-induced ototoxicity in
      children.
AB  - Platinum is extensively used in the treatment of several childhood cancers.
      However, ototoxicity is one of the most notable adverse effects, especially in
      children. Several studies suggest that genetics may predict its occurrence. Here,
      polymorphisms associated with platinum-induced ototoxicity were selected from the
      literature and were investigated in a pediatric population treated with platinum
      based agents. In this retrospective study, patients treated with cisplatin and/or
      carboplatin were screened. The patients with pre- and post-treatment audiogram
      (Brock criteria) available were included. We selected polymorphisms that have
      previously been associated with cisplatin ototoxicity with a minor allele
      frequency >=30%. Deletion of GSTM1 and GSTT1, rs1799735 (GSTM3), rs1695 (GSTP1),
      rs4880 (SOD2), rs2228001 (XPC), rs1799793 (XPD) and rs4788863 (SLC16A5) were
      investigated. Data of one hundred and six children matching the eligible criteria
      were analyzed. Thirty-three patients (31%) developed ototoxicity (with a Brock
      grade >=2). The probability of hearing loss increased significantly in patients
      carrying the null genotype for GSTT1 (P = 0.03), A/A genotype at rs1695 (P =
      0.01), and C/C genotype at rs1799793 (P = 0.008). We also showed an association
      of the cumulative doses of carboplatin with cisplatin ototoxicity (P <0.05). To
      conclude, deletion of GSTT1, rs1695 and rs1799793 may constitute potential
      predictors of platinum-induced ototoxicity.

PMID- 30112117
TI  - Stem-like and highly invasive prostate cancer cells expressing CD44v8-10 marker
      originate from CD44-negative cells.
AB  - In human prostate cancer (PCa), the neuroendocrine cells, expressing the prostate
      cancer stem cell (CSC) marker CD44, may be resistant to androgen ablation and
      promote tumor recurrence. During the study of heterogeneity of the highly
      aggressive neuroendocrine PCa cell lines PC3 and DU-145, we isolated and expanded
      in vitro a minor subpopulation of very small cells lacking CD44 (CD44neg).
      Unexpectedly, these sorted CD44neg cells rapidly and spontaneously converted to a
      stable CD44high phenotype specifically expressing the CD44v8-10 isoform which the
      sorted CD44high subpopulation failed to express. Surprisingly and potentially
      interesting, in these cells expression of CD44v8-10 was found to be induced in
      stem cell medium. CD44 variant isoforms are known to be more expressed in CSC and
      metastatic cells than CD44 standard isoform. In agreement, functional analysis of
      the two sorted and cultured subpopulations has shown that the CD44v8-10pos PC3
      cells, resulting from the conversion of the CD44neg subpopulation, were more
      invasive in vitro and had a higher clonogenic potential than the sorted CD44high
      cells, in that they produced mainly holoclones, known to be enriched in stem-like
      cells. Of interest, the CD44v8-10 is more expressed in human PCa biopsies than in
      normal gland. The discovery of CD44v8-10pos cells with stem-like and invasive
      features, derived from a minoritarian CD44neg cell population in PCa, alerts on
      the high plasticity of stem-like markers and urges for prudency on the approaches
      to targeting the putative CSC.

PMID- 30112116
TI  - ST2/IL-33 signaling promotes malignant development of experimental squamous cell
      carcinoma by decreasing NK cells cytotoxicity and modulating the intratumoral
      cell infiltrate.
AB  - Squamous cell carcinoma (SCC) is the second most common form of skin cancer and
      the mechanism(s) involved in the progression of this tumor are unknown. Increases
      in the expression of IL-33/ST2 axis components have been demonstrated to
      contribute to neoplastic transformation in several tumor models and interleukin
      33 is correlated with poor prognosis of patients with squamous cell carcinoma of
      the tongue. Based on these observations, we sought to determine the role of the
      IL-33/ST2 pathway during the development of SCC. Our findings show that ST2
      deficiency led to a marked decrease in the severity of skin lesions, suggesting
      that ST2 signaling contributed to tumor development. An analysis of tumor lesions
      in wild-type and ST2KO mice revealed that a lack of ST2 was associated with
      specific and significant reductions in the numbers of CD4+ T cells, CD8+ T cells,
      dendritic cells, and macrophages. In addition, NK cells that were isolated from
      ST2KO mice exhibited higher cytotoxic activity than cells isolated from wild-type
      mice. Notably, ST2 deficiency resulted in lower IFN-gamma, TNF-alpha, IL-10, and
      IL-17 production in tumor samples. Our findings indicate that the IL-33/ST2
      pathway contributes to the development of SCC by affecting leukocyte migration to
      tumor microenvironment and impairing NK cytotoxic activity.

PMID- 30112118
TI  - Protection from chemotherapy- and antibiotic-mediated dysbiosis of the gut
      microbiota by a probiotic with digestive enzymes supplement.
AB  - There are numerous downstream consequences of marketed drugs like antineoplastic
      agents on the gut microbiome, an effect that is suggested to contribute to
      adverse event profiles and may also influence drug responses. In cancer, progress
      is needed toward modulation of the host microbiome to prevent off-target side
      effects of drugs such as gastrointestinal mucositis that result from gut
      dysbiosis. The objective of this study was evaluation of the bioactivity of a
      supplement consisting of capsules with a blend of 9 probiotic organisms of the
      genera Lactobacillus and Bifidobacterium plus 10 digestive enzymes, in protecting
      the human gastrointestinal tract from chemotherapy and an antibiotic. We used the
      Simulator of Human Intestinal Microbial Ecosystem (SHIME) model, an in vitro
      model of a stable colon microbiota, and introduced 5-fluorouracil (5-FU) and
      vancomycin as microbiome-disrupting drugs. The probiotic with digestive enzymes
      supplement, added in capsules at in vivo doses, improved fermentation activity in
      the colon reactors and accelerated the recovery of microbial populations
      following 5-FU/vancomycin treatment. The supplement restored the Bacteroidetes to
      Firmicutes ratios in the colon reactors, increased the diversity of microbiota,
      and induced the production of microbial metabolites that elicited anti
      inflammatory cytokines in an in vitro model of intestinal inflammation. In the
      proximal colon, preventative administration of the supplement resulted in full
      recovery of the gut microbial community after cessation of 5-FU and vancomycin
      treatment. These results identify a probiotic with digestive enzymes formulation
      that protects against drug-induced gut dysbiosis, highlighting its potential
      utility as a component of routine cancer care.

PMID- 30112119
TI  - Correction: Mutations in the DNA methylation pathway and number of driver
      mutations predict response to azacitidine in myelodysplastic syndromes.
AB  - [This corrects the article DOI: 10.18632/oncotarget.22157.].

PMID- 30112120
TI  - Correction: Selenoprotein K deficiency inhibits melanoma by reducing calcium flux
      required for tumor growth and metastasis.
AB  - [This corrects the article DOI: 10.18632/oncotarget.24388.].

PMID- 30112121
TI  - Lumbar Spinal Stenosis: The Reliability, Sensitivity and Specificity of the Nerve
      Root Sedimentation Sign.
AB  - Introduction: This study is to evaluate the reliability, sensitivity and
      specificity of nerve root sedimentation sign (NRS) in our populations. The NRS is
      a radiological sign to diagnose lumbar spinal stenosis (LSS). It is claimed to be
      reliable with high sensitivity and specificity. Materials and Methods: A total of
      82 MRI images from 43 patients in Group A (LSS) and 39 patients in Group B (non
      LSS) were analysed and compared for the presence of the NRS sign. Two assessors
      were used to evaluate intra and inter-assessor reliability of this sign based on
      56 (33 patients, Group A and 23 patients, Group B). The findings were
      statistically analysed using SPSS software. Results: There was a significant
      association between spinal claudication and leg numbness with LSS (p<0.001 and
      Kappa=0.857, p<0.001). The inter-assessor reliability was also good (Kappa of
      0.786, p<0.001). Conclusion: The NRS sign has high sensitivity and specificity
      for diagnosing LSS. The sign also has good intra and inter-assessor reliability.

PMID- 30112122
TI  - Closed Intramedullary Locking Nailing for Metacarpal Fractures: A Retrospective
      Study of Sixty-Six Fractures.
AB  - Introduction: Metacarpal fractures are frequent injuries in the young male
      working population and the majority are treated non-operatively. There is a
      growing trend to surgically treat these fractures, with the aim of reducing the
      deformity and shortening the rehabilitation period. The aim of this retrospective
      case series is to report on our experience and clinical outcomes of using
      percutaneous flexible locking nails for the management of displaced metacarpal
      fractures. This study is a retrospective review of 66 fractures that were managed
      at our centre over a 7-year period. Materials and Methods: Records of 60 patients
      were retrospectively reviewed. Indications for surgery were a displaced
      metacarpal shaft or neck fracture with associated rotational deformity, or
      multiple metacarpal fractures. The fracture was reduced by closed manipulation,
      and a flexible pre-bent locked intramedullary nail (1.6mm diameter) was inserted
      through a percutaneous dorsal antegrade approach, facilitated by a specially
      designed pre-fabricated awl. The implant was removed at union. Patients were
      followed-up in clinic until the fracture had united. Results: The mean union time
      was seven weeks (range 2 to 22 weeks) and there were nine (14%) delayed unions
      (>3 months) and no non-unions. The nail had migrated in three cases (5%) and
      caused skin impingement in two cases (3%). There was one infected case (2%).
      Rotational clinical deformity was evident for two (3%) cases. Conclusion: The use
      of a minimally-invasive locked intramedullary nailing for unstable metacarpal
      fractures has a significantly low complication rate, with predictable union times
      and good functional outcomes.

PMID- 30112123
TI  - Are Gap and Cast Indices Predictors of Efficacy of Reduction in Fractures of Both
      Bones of the Leg? A Cohort Study.
AB  - Introduction: Non-operative management has successfully been practised for long
      in diaphyseal fractures of both bones of the leg. This study attempts to
      establish an acceptability criteria for plaster cast in order to predict future
      loss of reduction and its adequacy. Materials and Methods: A total of forty
      subjects were included as per inclusion-exclusion criteria. Gap and cast indices
      were calculated in the immediate post reduction phase and at third week follow-up
      visit. Results: The mean values of gap and cast indices in the immediate post
      reduction phase were 0.35+/-0.220 and 0.99+/-0.08 respectively and at the third
      week follow-up the mean value for both the parameters in those without loss of
      reduction were 1.11+/-0.50 and 1.03+/-0.09 respectively and in those with loss of
      reduction were 0.84+/-0.44 and 1.01+/-0.06 respectively. Conclusion: Gap and cast
      indices are not informative in assessing adequacy of reduction in diaphyseal
      fractures of both bones of the leg.

PMID- 30112124
TI  - Complex Proximal Humeral Fracture Fixation with PHILOS Plate using Minimal
      Invasive Percutaneous Plate Osteosynthesis (MIPPO) Technique: A Series of 30
      Patients.
AB  - Introduction: Proximal humerus fracture fixation using plate osteosynthesis
      depends on the quality of the bone, design of the fixation devices and intra
      operative soft tissue dissection. This study evaluates the functional outcome of
      minimally invasive percutaneous plate osteosynthesis using locking compression
      plate in proximal humerus fracture treatment. Materials and Methods: The study
      was conducted on 30 patients with complex proximal humerus fractures treated by
      minimally invasive percutaneous plate osteosynthesis using locking compression
      plate (PHILOS). There were 21 males and 9 females. The average age of our study
      group was 58.8 years. All the patients were evaluated at six weeks, three months,
      four months, six months and 12 months following surgery. Results: All patients
      had fracture union at an average of 13.2 weeks. The mean DASH score at the follow
      up was 8.69 (2.5 to 17.16), the average range of flexion was 143.83 degrees (100
      to 170 degrees) and abduction was 121.49 degrees (90 to 160 degrees). We had
      superficial infection in three patients which resolved with a short course of
      antibiotics. There was excellent outcome in 26 patients, good and fair in two
      patients each. Conclusion: Proximal humerus fractures treated with minimally
      invasive percutaneous plate osteosynthesis using locking compression plate with
      minimal soft tissue dissection, provides good functional outcome and early return
      of shoulder function.

PMID- 30112125
TI  - Do Age and Co-morbidy, Among other Factors, affect Length of Hospital Stay
      following Total Knee Arthroplasty.
AB  - Introduction: The only treatment for grade IV knee osteoarthritis is total knee
      arthroplasty (TKA) irrespective of the age of the patient. Most of the grade IV
      OA patient are elderly and most likely to have some comorbidities. Age and
      comorbidities are the major reasons for patient's reluctance to undergo TKA. A
      clinical pathway with standard length of stay (LOS) could justify the patient's
      hesitation for TKA. The aim of this study was to determine the factors, including
      age and comorbidity, that affect the LOS of patients treated with TKA. Materials
      and Methods: This is a retrospective study of TKA patients in Surabaya
      Orthopedics and Traumatology Hospital from January 2011 to July 2017.
      Preoperative comorbidities were scored using Charlson Comorbidity Index (CCI) and
      physical status by ASA (American Society of Anesthesiologist), classification for
      age, sex, BMI, blood loss, operation time, method of anaesthesia and
      postoperative day of rehabilitation were recorded as factors potentially
      affecting LOS. The discharge criteria for the patients were ability to ambulate
      to the bathroom and clean operative wound with no complications. The data
      obtained were analysed statistically. Results: The average LOS was 5.58 days,
      ranging from three to eight days. There were no demographic factors that affected
      the patients' LOS. BMI, ASA, CCI, and blood loss did not significantly affect
      LOS. Operation time was between 90-140 minutes, and spinal anaesthesia showed
      significant longer LOS, but within the average. Conclusion: Age and comorbidity
      did not affect length of stay in TKA patients.

PMID- 30112126
TI  - Acromio-Clavicular Joint Dislocation Types IV to VI: Does the Outcome with the
      modified Weaver-Dunn Procedure Justify the Treatment?
AB  - Introduction: The optimal surgical treatment for acromioclavicular joint (ACJ)
      injuries remains controversial. The modified Weaver-Dunn (WD) procedure is one of
      the frequently used techniques. Recently when it was compared with anatomical
      autogenous tendon graft reconstruction procedures, the results were inferior.
      However, these anatomical procedures are technically more demanding with small
      margin of error and they have tendency for postoperative pain because of extra
      donor site incision. Materials and Methods: Forty patients with type IV to VI ACJ
      dislocations were treated by modified WD procedure using non-absorbable synthetic
      suture passed through the base of coracoid process for augmentation of
      transferred coraco-acromial (CA) ligament. Functional outcome was assessed using
      the Oxford Shoulder Score, Nottingham Clavicular Score and Visual Analog Score
      (VAS) at the final follow-up after surgery. Results: The mean pre-operative
      Oxford Shoulder Score improved from 25.22+/-2.64 (range 20 to 30) to 44.75+/-1.99
      (range 40 to 48) and mean pre-operative Nottingham Shoulder Score improved from
      49.25+/-4.91 (range 39 to 58) to 87.27+/-4.39 (range 79 to 96) at last follow-up
      after surgery with p-value <0.001. Thirty-five (87.5%) patients had excellent
      outcomes, four (10%) patients had good outcomes and one (2.5%) patient had fair
      outcome. Thirty-eight (95%) patients had no pain while two (5%) had moderate pain
      based on VAS score. Conclusion: Modified Weaver-Dunn is a simple well established
      technique for grade IV to VI ACJ dislocation. We cannot consider this procedure
      as old and outdated on the argument that the long term functional outcomes are
      not suboptimal.

PMID- 30112127
TI  - Microgrids: A Model for Basic Microsurgery Skills Training.
AB  - Introduction: Microsurgery is a subspecialised field which requires high
      technical skill. Laboratory training offers good opportunity for novice surgeons
      to learn and repetitively practise their skills prior to hands-on clinical
      practice. Commonly, the training programme consists of models in a stepwise
      increase in fidelity: from latex sheet to anaesthetised rat. We introduce
      microgrids model as a daily warm up procedure in a 5-day basic microsurgery
      course. The purpose of this study is to evaluate the correlation between
      microgrids colouring under magnification with microsuturing proficiency among
      novice surgeons. Materials and Methods: Participants were required to fill in
      microgrids under magnification everyday during their 5-day training as a starter
      test. The number of completely filled in microgrids in 20 seconds was recorded. A
      simulated cut on latex sheet was sutured and the time taken to apply five sutures
      was recorded. The sutures were evaluated with modified Global Rating Scale (GRS).
      Data was analysed with SPSS. Results: There was a statistically significant
      correlation between the number of microgrids coloured and the time taken to apply
      five sutures (p<0.01). An increase in number of microgrids coloured was
      significantly associated with the increase in quality of the suturing technique
      (p< 0.01). During the 5-day basic microsurgery skills training for novice
      surgeons, microsuturing skill improvement correlated with microgrid colouring.
      Conclusion: Microgrids colouring reflected microsuturing proficiency. It is an
      inexpensive, readily available, and simple model of 'warm up' for hand dexterity.
      The microgrids model can function as a starter test for initial training and a
      quick screening measure to assess microsurgical skill.

PMID- 30112128
TI  - Proposal for a Radiological Classification System for Carpo-Metacarpal Joint
      Dislocations with or without Fractures.
AB  - Introduction: Though complex injuries like CarpoMetacarpal (CMC) Joint
      dislocations represent only 1% of all hand injuries, they have disabling impact
      on the functional status of patient. There are no reports in the literature
      classifying disabling complex injuries like CMC joint dislocations presumably
      because of low incidence. We propose a new classification through retrospective
      analysis of patients, along with literature search. Materials and Methods: A new
      classification system has been proposed and designed at our clinical unit and
      applied to eight patients with CMC joint dislocations. All patients were treated
      with open reduction with Kirschner wire fixation. At follow-up all these patients
      were analysed for radiographic assessments and functional scores. Results: The
      proposed classification identifies three types of dislocations and an additional
      complex category to supplement any basic type. The direction of dislocation
      describes the types as Type A: Dorsal, Type B: Volar and Type C: Divergent. Among
      the eight patients in our study, we had two of Type A, two Type B, three Type
      B.1, one Type C. 1. These patients had average follow-up of 18 months. The quick
      DASH score improved from 75.76 at 6 weeks to 1.9 at 18 months. We also did intra
      observer and inter-observer reliability which scored 1. Conclusion: Our proposal
      is a reproducible, simple, comprehensive and practical classification, easily
      remembered and communicated among colleagues. It is clinically relevant as it
      helps us in planning surgical management and prognostic evaluation.

PMID- 30112129
TI  - Bilateral Talus and Navicular Fractures accompanied with Unilateral Calcaneal
      Fracture: A Case Report.
AB  - An 18-year old male patient, with a history of paragliding accident, sustaining a
      coronal shear fracture of the body of the talus, an anterior process fracture of
      the calcaneus extending to the calcaneocuboid joint and a nondisplaced navicular
      body fracture at the right foot and a displaced fracture of the navicular body
      accompanied with posteromedial process fracture of the talus at the left side was
      referred to our emergency clinic. For the right foot, the coronal plane fracture
      of the talar body was anatomically reduced and fixed with screws. For the left
      foot, screw fixation was performed through the lateral aspect to fix the large
      posteromedial fragment. Small bone fragments were removed from the left navicular
      fracture, and the main fragments were also fixed with screw. The talo-navicular
      joint was stabilised with a Kirschner wire. At 36 months follow-up, bilateral
      foot and ankle functions were satisfactory, Maryland scores of the right and left
      foot were 85 (good) and 90 (excellent), respectively, and the patient regained
      his full activity level by the 5th month postoperatively. With reference to the
      number and types of fractures in this one patient, we present a standard protocol
      for treatment of isolated talus, navicular and calcaneal fractures presenting
      together in a single foot injury.

PMID- 30112130
TI  - Severe Sub-Acromial Bursitis with Rice Bodies in a Patient with Rheumatoid
      Arthritis: A Case Report and Review of Literature.
AB  - Multiple rice body formation is a rare presentation of chronic sub-acromial
      bursitis secondary to extensive underlying rheumatoid arthritis, sero-negative
      inflammatory arthritis or tuberculous joints. Although there is usually an
      accompanying inflammatory arthropathy, it can occur in the absence of any
      underlying systemic disorder. We report a case of five years old neglected rice
      body deposition in shoulder in a 54-years old lady diagnosed to be having
      rheumatoid arthritis. After initial investigations, arthroscopic removal of rice
      bodies with bursa excision relieved the symptoms. The underlying rheumatic
      condition continued its course, generally sparing the involved shoulder joint. We
      suggest thorough examination for systemic rheumatologic disease in patients
      diagnosed with such lesions.

PMID- 30112132
TI  - Atraumatic Insufficiency Fractures of the Tarsal Bones - An Unusual Cause of
      Recurrent Heel Pain in a Patient with Rheumatoid Arthritis: A Case Report.
AB  - The incidence of insufficiency fractures is approximately 1% in rheumatoid
      arthritis patients. The predisposing factors are chronic inflammation, skeletal
      deformities, biomechanical stresses and osteoporosis. The medications used in the
      treatment of rheumatoid arthritis such as Glucocorticosteroids and Methotrexate
      also contribute to the development of osteoporosis and insufficiency fractures. A
      68-year old lady who was suffering from rheumatoid arthritis and on long term
      Methotrexate was seen in the outpatient clinic with recurrent episodes of heel
      pain. Examination revealed diffuse tenderness around the heel with full range of
      ankle movements but painful limitation of subtalar joint movements. Radiographic
      examination of the ankle showed a highly suspicious fracture of the calcaneus and
      confirmed on MRI as an insufficiency fracture. She was treated successfully with
      oral bisphosphonates and moon boot brace. She presented after two years with
      recurrent episodes of heel pain. The plain radiograph and MRI scan confirmed an
      insufficiency fracture of the talus. She was treated non-operatively with
      intravenous Zolendronic acid and bracing. In chronic rheumatoid arthritis
      patients especially on Methotrexate and Glucocorticoids a high index of suspicion
      of insufficiency fractures should be considered if they present with bone pain.
      MRI scan is the investigation of choice and is conclusive.

PMID- 30112131
TI  - Discal Cyst of the Lumbar Spine: Case Report of a Rare Clinical Entity.
AB  - Being a rare clinical entity, discal cyst presents indistinguishably from other
      causes of lower back pain and radiculopathy. It is an extremely rare pathology
      with unclear pathogenesis, indeterminate natural history with no consensus on the
      ideal management of the condition. We report a rare case of discal cyst in a
      patient who presented to our centre with localised low back pain and subsequently
      left sided radicular pain. With the aid of MRI and with clear surgical indication
      we proceeded with endoscopic removal of the cyst and intraoperatively confirmed
      its origin from the adjacent disc. The patient had immediate relief of his
      symptoms and no postoperative complications. We recommend that endoscopic surgery
      can be an effective alternative to conventional open surgery for discal cyst of
      the lumbar spine.

PMID- 30112133
TI  - Fracture and Posterior Dislocation of Meniscal Bearing Insert in Mobile Bearing
      Unicompartmental Knee Arthroplasty: A Case Report.
AB  - Dislocation of meniscal bearing insert is a rare but well-recognised complication
      in meniscal bearing unicompartmental knee arthroplasty (UKA). On the other hand,
      fracture of meniscal bearing insert of phase III Oxford UKA has only been
      reported once in the current literature. The authors report a case of fracture
      and posterior dislocation of one of the fragments of the meniscal bearing insert
      in a mobile bearing medial UKA. The fracture was only diagnosed during the
      revision surgery. The posteriorly dislodged fragment was subsequently retrieved
      through the same skin incision and a new polyethylene insert of the same size was
      implanted.

PMID- 30112134
TI  - Neglected Anterior Dislocation of the Elbow Joint: Case Report of a Rare Injury.
AB  - We present an unusual case of five months old neglected anterior dislocation of
      the right elbow joint in a 19-year old man. The patient had been initially
      treated by a traditional bone setter, but the elbow remained unreduced. He
      presented to us with pain, deformity and limited range of motion of his right
      elbow joint. Radiographs revealed an unreduced anterior dislocation of the right
      elbow joint. We describe the problems encountered during open reduction and
      rehabilitation and result one year after the operation with the patient having a
      stable elbow and a functional range of motion.

PMID- 30112135
TI  - A New Approach to Body Donation for Medical Education: The Silent Mentor
      Programme.
AB  - Cadaveric dissection is an integral component of medical education. There had
      been concerns about negative impact on medical students exposed to deceased
      donors before their clinical years, but most studies reported overall positive
      outcome following this form of teaching. Due to reducing number of body donations
      in most parts of the world, many institutions are adopting alternative models
      especially for the teaching of gross anatomy. A new body donation programme that
      incorporate humanistic values in the procurement process was initiated by Tsu Chi
      University of Taiwan in 1996. Early observations following teaching with the so
      called "silent mentors" noted less negative emotional impact on the students.
      With increasing number of body donation following the initiation of the silent
      mentor programme as reported in some regions, we will be able to continue the
      time-honoured cadaveric dissection for anatomy teaching, at the same time
      promoting humanistic values on junior doctors.

PMID- 30112136
TI  - Paediatric Femur Fractures: A Plea for Minimally Invasive Surgery to Prevent
      Osteomyelitis.

PMID- 30112137
TI  - Neuronal Cell Death and Mouse (Mus musculus) Behaviour Induced by Bee Venom.
AB  - Neuronal cell death can occur in a tissue or organ, including the brain, which
      affects memory. The objectives of this study were to determine the dose of bee
      venom that causes neuronal death and analyse the alteration of mouse behaviour,
      focusing in particular on spatial memory. Fifteen male mice of Deutsche Denken
      Yoken (DDY) strain were divided into control and treatment groups. Bee venom was
      injected six times for two weeks intraperitoneally with 1.88 mg/kg, 3.76 mg/kg,
      5.6 mg/kg, and 7.48 mg/kg doses of venom. Brain histology was studied using
      haematoxylin-eosin stained paraffin embedded 5 MUm coronal sections. A Y maze
      test was used to assay behaviour. Parameters observed were the number of dead
      neurons and the percentage of mice with altered behaviour. ANOVA showed that the
      effects of bee venom were significantly different in the case of the neuronal
      death parameter but were not significantly different in the case of the mice
      behaviour parameter. Duncan's Multiple Range Test (DMRT) demonstrated that P4
      (7.48 mg/kg) gave the highest effect of bee venom to promote neuronal death.

PMID- 30112138
TI  - Phylogenetic Relatedness of Several Agarwood-Producing Taxa (Thymelaeaceae) from
      Indonesia.
AB  - Indonesia is home to several tree taxa that are harvested for agarwood. This
      highly valuable oleoresin ironically was the cause for some species to become
      vulnerable due to gluttonous human activity. However, information on the genetic
      diversity of these endangered trees is limited. In this study, 28 specimens
      representing eight species from two genera, Aquilaria and Gyrinops, were
      collected from ex-situ and in-situ populations in Indonesia. Phylogenetic
      analysis conducted on DNA sequences of the nuclear ribosomal internal transcribed
      spacer (ITS) and the trnL-trnF intergenic spacer regions, revealed that Aquilaria
      and Gyrinops are paraphyletic when Aquilaria cumingiana is excluded. The
      phylogenetic analysis for ITS and trnL-trnF showed capability to categorise
      agarwood-producing species based on their regions: East Indonesia and West
      Indonesia, using Wallace's Line as the divider. In addition, we discuss
      challenges in species identification and taxonomy of agarwood-producing genera,
      and their conservation efforts in Indonesia.

PMID- 30112139
TI  - Resistance Response of Chilli (Capsicum annuum L.) F1 to Fusarium oxysporum
      Involves Expression of the CaChi2 Gene.
AB  - Cross-breeding is a method of producing progeny with better resistance to
      pathogens. Resistance to pathogens usually involves pathogenesis-related (PR)
      proteins. Class II chitinase is an example of a defensive PR protein in plants.
      The class II chitinase in chilli is coded by the CaChi2 gene. In this study, we
      crossed susceptible with resistant chilli cultivars, analysed the F1 resistance
      response against pathogenic F. oxysporum, and analysed the level of CaChi2 gene
      expression in the F1. Data were collected using disease severity index (DSI)
      determination and gene expression analysis by qRT-PCR (quantitative Reverse
      Transcriptase Polymerase Chain Reaction). Results showed that the DSI of F1 was
      not significantly different from the resistant ancestor. The relative CaChi2
      expression level of F1 was higher than the susceptible ancestor but not
      significantly different from the resistant ancestor. We concluded that the F1 can
      be categorised as resistant to F. oxysporum, and the CaChi2 gene is involved in
      the molecular defense response.

PMID- 30112140
TI  - The Antibacterial Activity of Dayak Onion (Eleutherine palmifolia (L.) Merr)
      towards Pathogenic Bacteria.
AB  - Antibacterial activity of indigenous Dayak onion (Eleutherine palmifolia (L.)
      Merr) was investigated. The Dayak onion was solvent extracted with n-hexane,
      ethyl acetate, and ethanol 96% consecutively. Each extract was tested its
      antibacterial activity towards methicillin-resistant Staphylococcus aureus
      (MRSA), Bacillus cereus, Shigella sp., and Pseudomonas aeruginosa using disc
      diffusion method. The test results showed that the n-hexane, ethyl acetate, and
      ethanol 96% extracts positively inhibited the growth of MRSA, B. cereus, Shigella
      sp., and P. aeruginosa. The highest inhibition activity of each extract was
      obtained with 10 mg/mL of extract concentration; whereas the minimum inhibitory
      concentration (MIC) of each extract was 2 mg/mL. Extract with the highest
      inhibition activity was ethyl acetate extract against B. cereus (139.58%). TLC
      evaluation of ethyl acetate extract showed four spots and bioautography indicated
      that ethyl acetate extract contained four types of compounds with inhibition
      activity against B. cereus, in which two compounds have higher antibacterial
      activity than the other two.

PMID- 30112142
TI  - Declining Orangutans Population in the Unprotected Forest of Batang Toru.
AB  - Habitat loss and hunting are major threats to the long-term survival of the
      viable orangutan population in Batang Toru. East Batang Toru Forest Block (EBTFB)
      is the most threatened area due to low forest cover and high encroachment. Based
      on a preliminary survey in 2008, Hopong forest which is located in EBTFB, had the
      highest orangutan density (0.7 ind/km2). However illegal logging and hunting of
      protected species were occuring in this unprotected forest. Since this location
      has been gazetted as unprotected forest from the first survey until this study
      was conducted, it is important to assess orangutans population trends. This study
      aims to provide an updated density of orangutan in Hopong forest. The study
      included the location of the original survey but covered a wider overall area.
      The line transect method was used to record orangutan nests, ficus and trees
      bearing fruits. A quadrat method was used to record vegetation. The encounter
      rate of orangutan declined from 0.7 ind/km2 to 0.4 ind/km2 between 2008 and 2015.
      Forest cover has also changed in the seven years between surveys and this has
      influenced orangutan and orangutan nest encounter rates in Hopong. Since
      unprotected forest is at more risk in comparison with protected forest,
      allocation status of the Hopong forest is critical to reduce the threats it
      faces.

PMID- 30112143
TI  - Insecticidal Activity of Grape Pomaces from Two Grape Cultivars Against the
      Housefly (Musca domestica L.) Under Laboratory Conditions.
AB  - Aqueous extracts prepared from the powdered entire pomaces and their parts (seeds
      and peels) of two Iraqi grape cultivars (Shada and Des-Alanez) were evaluated for
      their ovicidal, larvicidal, and pupicidal activities against housefly, Musca
      domestica (Linnaeus 1758) and compared them with chemical insecticide (Agita 10
      WG; Austria). The highest insecticidal activity was shown by the aqueous extracts
      of powdered seeds followed by the entire pomace and then peels. The water
      extracts from the seeds, peels and pomaces were able to inhibit completely the
      hatching of the eggs at a concentration of 150 MUg/ml while the Agita insecticide
      was able to inhibit the hatching process at a concentration of 50 MUg/ml. The
      water extracts also were able to kill the L3 larvae and the activity was
      increasing with the increasing of the concentration. It is very interesting to
      note that the addition of the powdered entire pomaces, seeds, and peels on top or
      at the bottom of the cow manure was able to inhibit the development of up to 50%
      and 47.5% of L1 to pupae and to adult flies, respectively. Taking into
      consideration the huge amounts of grape pomaces that produced annually, the cheap
      price and the ease in dealing with, make them a good candidate as alternative
      insecticides and environmentally more friendly than the chemical insecticides.

PMID- 30112141
TI  - Apoptosis Activity of the Mouse Macrophage Cell Line J774A.1 Infected with a
      Recombinant BCG consisting the C-Terminus of Merozoite Surface Protein-1 of
      Plasmodium falciparum.
AB  - Macrophage apoptosis exerts an efficient mechanism in controlling intracellular
      infection during innate immune response against various pathogens including
      malaria parasites. This study was carried out to determine the apoptosis activity
      in mouse macrophage cell line J774A.1 infected with a Mycobacterium bovis bacille
      Calmette-Guerin (BCG) clone and a recombinant BCG clone expressing the C-terminus
      of merozoite surface protein-1 (BCG-MSP1C) of Plasmodium falciparum for 48 h. In
      this study, a parent BCG cells was used as a control. The nuclear staining with
      Hoechst 33342 showed that the BCG-MSP1C cells was capable of increasing the
      nuclear condensation and morphological stages of apoptosis in the infected cells
      compared to the BCG-infected cells and the lipopolysaccharide (LPS)-stimulated
      cells. The flow cytometric analysis using Annexin-V and Propidium iodide (PI)
      staining confirmed that the BCG-MSP1C cells significantly increased the
      percentage of early apoptotic activity in the infected macrophage higher than the
      one stimulated by the parent BCG cells and LPS. This apoptotic response
      corresponded with the reduction of the anti-apoptotic Bcl-2 protein expression
      and higher p53 expression. The colorimetric assay demonstrated that the BCG cells
      capable of stimulating higher production of caspase-1, -3, -8 and -9 while the
      BCG-MSP1C cells stimulated the expression of caspase-1 and -9 in the infected
      macrophages, suggesting the involvement of mitochondrial-mediated (intrinsic)
      pathway of apoptosis. In conclusion, both the BCG and BCG-MSP1C cells are capable
      of inducing macrophage apoptosis activity in the mouse macrophage cell line
      J774A.1. This mechanism is important for the elimination of pathogens such as
      malaria parasite during the phagocytosis activity of macrophage. However, the BCG
      MSP1C cells showed higher apoptosis activity than those produced by the parent
      BCG cells.

PMID- 30112144
TI  - Muscle Fatty Acid Content in Selected Freshwater Fish from Bukit Merah Reservoir,
      Perak, Malaysia.
AB  - One of the oldest reservoirs in Peninsular Malaysia, Bukit Merah Reservoir, is a
      place in which locals participate in fishing activities. Inland fisheries are
      important to individuals, society and the environment; whereby they generate a
      source of income and food security. It is essential to gauge the nutrition value
      of fish caught in this location as food source, especially in terms of fatty acid
      composition, to better demonstrate its potential towards the betterment of human
      health and general well-being. From an initial list of 47 fish species available
      in Bukit Merah Reservoir, a total of seven edible freshwater fish species were
      identified, namely tinfoil barb (Barbonymus schwanenfeldii), Javanese barb
      (Barbonymus gonionotus), hampala barb (Hampala macrolepidota), beardless barb
      (Cyclocheilichthys apogon), glassfish (Oxygaster anomalura), striped snakehead
      (Channa striata) and horseface loach (Acantopsis dialuzona), and muscle fatty
      acid content was analysed to determine their nutritional value. Muscle of
      cyprinid fish contained substantial amount of omega-3 long-chain polyunsaturated
      fatty acids (LC-PUFA) compared to fish from Channidae and Cobitidae families.
      Javanese and tinfoil barbs muscle recorded the highest levels of combined
      eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) indicating the highest
      nutritional value comparatively. Unexpectedly, the striped snakehead, a predatory
      carnivore, contained lower levels of LC-PUFA compared to detrivorous/herbivorous
      fishes. This further justifies that the omega-3 polyunsaturated fatty acids
      (PUFA) content in fish muscle varies according to their feeding habits. Even
      though it has been recommended that marine fish be consumed to improve health to
      a certain extent, there still are benefits of consuming freshwater fish, as there
      are several species which contain considerable amounts of beneficial omega-3
      PUFA.

PMID- 30112145
TI  - Shoot Induction in White Eggplant (Solanum melongena L. Cv. Bulat Putih) using 6
      Benzylaminopurine and Kinetin.
AB  - Solanum melongena L. commonly known as the eggplant or brinjal comes from the
      family of Solanaceae, sharing the same ancestor with the tomato and potato. It is
      an economically important crop worldwide, being well studied for its medicinal
      properties, nutritional values and its role as an alternative model plant. The
      eggplant fruit has been previously used for treatments of various diseases such
      as bronchitis, asthma, arthritis and diabetes as well as its nutritive properties
      that are beneficial to the human diet. Plant transformation studies on the
      eggplant have been widely done for the production of transgenic eggplants
      harbouring genes that are beneficial for optimal plant growth and fruit
      production. Shoot induction is an essential step required for the successful
      regeneration of transformed plant tissues and therefore is an essential pre
      requisite in Agrobacterium-mediated transformation. The local eggplant cv. Bulat
      Putih is a local cultivar of eggplant in Malaysia with white and round fruits
      making it a potential model plant colour pigment accumulation studies in fruit
      crops. The current work aims to investigate the shoot induction potential of 6
      benzylaminopurine (BAP) and Kinetin from cotyledon explants of eggplant cv. Bulat
      Putih. Results indicated that both BAP and Kinetin were able to induce the
      regeneration of callus from cotyledon explants. On the other hand, Kinetin at the
      concentration of 2.0 mg/L successfully induced shoots at the value of 1.50 +/-
      0.22 shoots per explant, whereas BAP alone did not trigger any formation of
      shoots. This study indicated that kinetin alone is sufficient to induce shoots in
      eggplant cv. Bulat Putih without the presence of BAP.

PMID- 30112146
TI  - Microbiota of Palm Oil Mill Wastewater in Malaysia.
AB  - This study was aimed at identifying indigenous microorganisms from palm oil mill
      effluent (POME) and to ascertain the microbial load. Isolation and identification
      of indigenous microorganisms was subjected to standard microbiological methods
      and sequencing of the 16S rRNA and 18S rRNA genes. Sequencing of the 16S rRNA and
      18S rRNA genes for the microbial strains signifies that they were known as
      Micrococcus luteus 101PB, Stenotrophomonas maltophilia 102PB, Bacillus cereus
      103PB, Providencia vermicola 104PB, Klebsiella pneumoniae 105PB, Bacillus
      subtilis 106PB, Aspergillus fumigatus 107PF, Aspergillus nomius 108PF,
      Aspergillus niger 109PF and Meyerozyma guilliermondii 110PF. Results revealed
      that the population of total heterotrophic bacteria (THB) ranged from 9.5 * 105 -
      7.9 * 106 cfu/mL. The total heterotrophic fungi (THF) ranged from 2.1 * 104 - 6.4
      * 104 cfu/mL. Total viable heterotrophic indigenous microbial population on CMC
      agar ranged from 8.2 * 105 - 9.1 * 106 cfu/mL and 1.4 * 103 - 3.4 * 103 cfu/mL
      for bacteria and fungi respectively. The microbial population of oil degrading
      bacteria (ODB) ranged from 6.4 * 105 - 4.8 * 106 cfu/mL and the oil degrading
      fungi (ODF) ranged from 2.8 * 103 - 4.7 * 104 cfu/mL. The findings revealed that
      microorganisms flourish well in POME. Therefore, this denotes that isolating
      native microorganisms from POME is imperative for effectual bioremediation,
      biotreatment and biodegradation of industrial wastewaters.

PMID- 30112147
TI  - Shoot Induction from Axillary Shoot Tip Explants of Fig (Ficus carica) cv.
      Japanese BTM 6.
AB  - Fig, or Ficus carica, is a fruit tree from the Moraceae family and is widely
      grown in tropical and subtropical regions of the world. Fig plants are mainly
      propagated through grafting, air layering, and hardwood cutting whereby these
      methods were found to be less efficient. Plant tissue culture is efficient method
      to propagate plants, particularly to produce true-to-type platelets for mass
      multiplication. The aim of this study is to induce multiple shoot formation on
      Ficus carica cv. Japanese BTM 6 through identifying and optimising the
      concentrations of 6-Benzylaminopurine (BAP) and Zeatin suited for shoot
      formation. The axillary shoot tip explants were cultured in MS media supplemented
      with different concentrations of BAP and Zeatin (0, 0.5, 1.0, 1.5 and 2.0 mg/L)
      to determine the optimal concentration for the formation of multiple shoots.
      Number of shoots per explants and the differences in shoot height of explants
      were calculated after 8 and 12 weeks of culture respectively. Of all the
      treatments of BAP, MS media containing with 2 mg/L BAP marked the highest number
      of shoots per explant with the average value of 1.67 +/- 0.33 while 1.5 and 2
      mg/L of BAP produced the highest differences in shoot height with 0.51 +/- 0.08
      cm and 0.51 +/- 0.07 cm after 12 weeks respectively. Murashige and Skoog (MS)
      media supplemented with 2 mg/L Zeatin showed the highest production of multiple
      shoots and differences in shoot height with the average of 0.83 +/- 0.219 and
      0.32 +/- 0.04 cm respectively among all the different treatments of Zeatin. In
      this study, BAP performed better in shoot induction and elongation as compared to
      Zeatin for the cultivar Japanese BTM 6.

PMID- 30112148
TI  - Lead Concentration in Long-Tailed Macaque (Macaca fascicularis) Hair in Kuala
      Selangor, Malaysia.
AB  - Long-tailed macaque (Macaca fascicularis) has the potential to be a good
      biological indicator for toxic exposure because they have an almost similar
      physiology and behaviour to humans. The objective of this study is to determine
      the concentration of lead (Pb) in hair samples of long-tailed macaques which were
      found in and out of the Kuala Selangor Nature Park (KSNP) area. The hypothesis is
      long-tailed macaques that live in the anthropogenic area (outside KSNP) may be
      exposed to high levels of lead compared to long-tailed macaques living in the
      forest area (inside KSNP). Analysis of hair samples were carried out using
      Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). The study found that the
      average mean of lead concentration in the anthropogenic area is 6.31 MUg/g while
      for the forest area it is 3.16 MUg/g. Lead concentration in the two areas are
      statistically insignificant. Nevertheless, lead concentration in the
      anthropogenic area recorded a slightly higher mean concentration than in the
      forest area. Even so, results of this study indicate that long-tailed macaques in
      Kuala Selangor are not exposed to high levels of lead. This study is the first in
      Malaysia to utilise long-tailed macaques as a biological indicator for testing
      the concentration of toxic substances in the environment. This study is still in
      its early stages; thus, future research requires improvements.

PMID- 30112149
TI  - Identification of Cultivable Bacteria from Tropical Marine Sponges and Their
      Biotechnological Potentials.
AB  - Marine sponges are acknowledged as bacterial hotspots in the oceanic biome.
      Aquatic bacteria are being investigated comprehensively for bioactive complexes
      and secondary metabolites. Cultivable bacteria associated with different species
      of sea sponges in South China Sea waters adjacent to Bidong Island, Terengganu
      were identified. Molecular identification was accomplished using 16S rRNA gene
      cloning and sequencing. Fourteen bacterial species were identified and their
      phylogenetic relationships were analysed by constructing a neighbour-joining tree
      with Molecular Evolutionary Genetics Analysis 6. The identified species
      encompassed four bacterial classes that were Firmicutes, Actinobacteria,
      Alphaproteobacteria and Gammaproteobacteria known to have been associated with
      sponges. The potential biotechnological applications of the identified bacteria
      were compared and reviewed based on relevant past studies. The biotechnological
      functions of the 14 cultivable isolates have been previously reported, hence
      reinforcing that bacteria associated with sponges are an abundant resource of
      scientifically essential compounds. Resilience of psychrotolerant bacteria,
      Psychrobacter celer, in warm tropical waters holds notable prospects for future
      research.

PMID- 30112150
TI  - Molecular Identification of Endophytic Fungi from Banana Leaves (Musa spp.).
AB  - Endophytic fungi are part of microbial community found in various types of plant
      tissues including the leave, and display a range of symbiotic interactions with
      the plant host. In this study, endophytic fungi isolated from banana leaves were
      identified using ITS (Internal Transcribed Spacer region) sequences of which 10
      genera comprising 17 species were molecularly identified. Endophytic fungal
      species identified were Nigrospora oryzae, Nigrospora sphaerica, Colletotrichum
      gloeosporioides, Colletotrichum siamense, Fusarium equiseti, Fusarium
      chlamydosporum, Phoma sorghina, Pestalotiopsis oxyanthi, Pestalotiopsis theae,
      Pestalotiopsis eugeniae, Penicillium steckii, Penicillium purpurogenum, Bipolaris
      papendorfii, Bipolaris sp., Lasidiodiplodia theobromae, Cochliobolus intermedius
      dan Aspergillus niger. The present study showed that several endophytic fungal
      genera/species are common plant pathogen and there is a possibility that these
      endophytes can become pathogenic. Some of the fungal endophyte might be mutualist
      or saprophyte.

PMID- 30112151
TI  - A Review of Gelatin Source Authentication Methods.
AB  - Gelatin is a very popular pharmaceutical and food ingredient and the most studied
      ingredient in Halal researches. Interest in source gelatin authentication is
      based on religious and cultural beliefs, food fraud prevention and health issues.
      Seven gelatin authentication methods that have been developed include: nucleic
      acid based, immunochemical, electrophoretic analysis, spectroscopic, mass
      spectrometric, chromatographic-chemometric and chemisorption methods. These
      methods are time consuming, and require capital intensive equipment with huge
      running cost. Reliability of gelatin authentication methods is challenged mostly
      by transformation of gelatin during processing and close similarities among
      gelatin structures. This review concisely presents findings and challenges in
      this research area and suggests needs for more researches on development of rapid
      authentication method and process-transformed gelatins.

PMID- 30112152
TI  - Prevalence and antimicrobial resistance of shiga toxin-producing Escherichia coli
      and enteropathogenic Escherichia coli isolated from patients with acute diarrhea.
AB  - Background and Objectives: Diarrheal disease is still a major health problem in
      developing countries, where it is considered as one of the leading causes of
      morbidity and mortality especially in children. Escherichia coli is one of the
      important enteropathogenic bacteria which causes diarrhea in people. The aim of
      this study was to investigate the prevalence and antimicrobial resistance of
      shiga toxin-producing E. coli (STEC), Enterohaemorrhagic E. coli (EHEC), and
      Enteropathogenic E. coli (EPEC) in fecal samples collected from patients with
      acute diarrhea in a number of Iranian provinces. Materials and Methods: A total
      of 102 strains of E. coli were isolated from fecal samples collected from
      patients with acute diarrhea using microbiological phenotypic tests. The
      antibiotic susceptibility pattern of all isolates was determined by the disk agar
      diffusion (DAD) method. The presence of eae, bfp, stx1, sts2 and EAF genes in the
      isolates was investigated by PCR. The results were analyzed by SPSS; version 17.0
      software. Results: Out of 102 E. coli isolates screened for specific genes, 52
      strains of E. coli were identified to harbor STEC 26 (50%), EPEC 13 (25%) and
      EHEC 13 (25%). Greatest resistance was observed to amoxicillin and ampicillin 40
      (76.9%), and most sensitivity to imipenem 52 (100%) and gentamicin 40 (76.9%). We
      also found that 80.77% of diarrheic E. coli isolates were multidrug resistant
      (MDR). Conclusion: The results showed that E. coli is one of the major causes of
      diarrhea and is highly resistant to commonly used antibiotics; therefore,
      officials must pay great attention to this issue in order to increase the health
      of the community.

PMID- 30112153
TI  - High frequency of exfoliative toxin genes among Staphylococcus aureus isolated
      from clinical specimens in the north of Iran: Alarm for the health of individuals
      under risk.
AB  - Background and Objectives: Exfoliative toxins (ETs) of Staphylococcus aureus are
      the main reason of scalded skin syndrome in infants and young children. The aim
      of this study was to investigate the prevalence of eta, etb and etd genes in S.
      aureus. Materials and Methods: A total of 150 S. aureus isolates were collected
      from clinical specimens during the years 2014 to 2016 in the north of Iran. After
      confirmation of the species using standard diagnostic procedures, polymerase
      chain reaction was used for detection of the eta, etb and etd genes among the
      isolates. Results: Overall, 131 (87.3%) isolates were positive for at least one
      of the ET genes; 115 (76.7%), 25 (16.7%) and 81 (54%) of the isolates carried the
      eta, etb and etd genes, respectively. Although eta and etd genes were present in
      all types of clinical samples, etb was found only in the wound, synovial fluid,
      sputum and tracheal aspirate. Overall, 7 toxin genotypes were observed, among
      which the genotypes eta-etd, eta and eta-etb-etd predominated at rates of 35.3%,
      26.7% and 9.3%, respectively. Conclusion: Detection of the high rate of
      prevalence of ET genes in the current study is considered as a serious problem
      because it is likely to spread and transfer these genes between strains.
      Furthermore, these isolates circulating in the community, particularly from
      infants, old people and immunocompromised patients, are important health-wise.

PMID- 30112154
TI  - Group B Streptococci and Trichomonas vaginalis infections in pregnant women and
      those with spontaneous abortion at Sanandaj, Iran.
AB  - Background and Objectives: Group B Streptococcali (GBS) is an important factor in
      newborn deaths in developed and developing countries. Trichomoniasis is one of
      the most prevalent sexually transmitted diseases (STDs) in the world, which is
      caused by protozoan Trichomonas vaginalis (T. vaginalis). The present study
      compares the frequency of GBS and T. vaginalis genital infections in pregnant
      women, women with spontaneous abortion, as well as its role in spontaneous
      abortion. Materials and Methods: In this case-control study, 109 women were
      included with spontaneous abortion with gestational ages between 11-20 weeks and
      109 pregnant women with gestational ages between 35-37 weeks in Sanandaj, Iran.
      DNA was extracted by endocervical swabs and subjected to PCR assays. The
      independent t-test was used; and for comparing other qualitative variables in
      each group, the Chi-Square Test was used. Results: The age of the women ranged
      from 19-43 years (29.6 +/- 5.9) and in the control group the age range was from
      19-42 years (27.8 +/- 4.87). The rate of prevalence of Group B Streptococcal
      infection in the control group was 3.6%; and in the patient group there were 7.2%
      with the rate of prevalence of T. vaginalis in both groups as zero. Conclusion:
      The present study showed that there is no relationship between GBS infections (P
      value = 0.235) and T. vaginalis.

PMID- 30112155
TI  - Antibacterial effects of microbial synthesized silver-copper nanoalloys on
      Escherichia coli, Burkholderia cepacia, Listeria monocytogenes and Brucella
      abortus.
AB  - Background and Objectives: Bacterial resistance is an emerging public health
      problem worldwide. Metallic nanoparticles and nanoalloys open a promising field
      due to their excellent antimicrobial effects. The aim of the present study was to
      investigate the antibacterial effects of Ag-Cu nanoalloys, which were
      biosynthesized by Lactobacillus casei ATCC 39392, on some of the important
      bacterial pathogens, including Escherichia coli, Burkholderia cepacia, Listeria
      monocytogenes and Brucella abortus. Materials and Methods: Ag-Cu nanoalloys were
      synthesized through the microbial reduction of AgNO3 and CuSO4 by Lactobacillus
      casei ATCC39392. Furthermore, they were characterized by Fourier-Transform
      Infrared Spectrometer (FTIR) and Field Emission Scanning Electron Microscopy
      (FESEM) analysis in order to investigate their chemical composition and
      morphological features, respectively. The minimum inhibitory and minimum
      bactericidal concentrations of Ag-Cu nanoalloys were determined against each
      strain. The bactericidal test was conducted on the surface of MHA supplemented
      with 1, 0.1, and 0.01 MUg/MUL of the synthesized nanoalloy. The antimicrobial
      effects of synthesized nanoalloy were compared with ciprofloxacin, ampicillin and
      ceftazidime as positive controls. Results: Presence of different chemical
      functional groups, including N-H, C-H, C-N and C-O on the surface of Ag-Cu
      nanoalloys was recorded by FTIR. FESEM micrographs revealed uniformly distributed
      nanoparticles with spherical shape and size ranging from 50 to 100 nm. The
      synthesized Ag-Cu nanoalloys showed antibacterial activity against L.
      monocytogenes PTCC 1298, E. coli ATCC 25922 and B. abortus vaccine strain.
      However, no antibacterial effects were observed against B. cepacia ATCC 25416.
      Conclusion: According to the findings of the present research, the microbially
      synthesized Ag-Cu nanoalloy demonstrated antibacterial effects on the majority of
      the bacteria studied even at 0.01 MUg/MUL. However, complementary investigations
      should be conducted into the safety of this nanoalloy for in vivo or systemic
      use.

PMID- 30112156
TI  - PCR-DGGE analysis of fungal community in manufacturing process of a traditional
      Iranian cheese.
AB  - Background and Objectives: The microbial communities of traditional milk-based
      food are of great importance in its manufacturing process, especially when using
      raw milk with natural cultures. Liqvan (Lighvan or Levan) is a traditional
      Iranian buried cheese, which is made from raw ewe's milk without a starter
      addition. The aim of this study was to explore the fungal active population
      during this cheese manufacturing process by comparing DNA and RNA based culture
      independent method Denaturing Gradient Gel Electrophoresis (DGGE). Materials and
      Methods: Four samples of each milk, curd and ripened cheese were collected from
      Liqvan village located in East Azerbaijan province of Iran. Total DNA and RNA of
      each sample were extracted and PCR amplicons of D1 region of 26S rRNA gene was
      targeted for DGGE analysis. This method applied at both DNA and RNA levels in
      order to examine which taxonomic groups of fungi are active at each step of
      ripening. Results: DGGE profiles of yeast amplicons showed different results
      between extracted DNA and RNA during ripening process. However, the main group
      that is present in all stages of ripening process belongs to the genus Candida
      although Kluyveromyces, Pichia, Galactomyces, Saccharomyces and Cryptococcus are
      most abundant fungi. Conclusion: As no starter culture added to Liqvan cheese it
      seems fungal diversity are mainly rely on the indigenous microbiota of milk.
      Furthermore, the percentage of the dominant fungal genera from the total
      sequences differed among DNA and cDNA libraries.

PMID- 30112157
TI  - Tracking leading anti-Candida compounds in plant samples; Plumbago europaea.
AB  - Background and Objectives: Due to the importance of finding new and more
      effective antifungal and antibacterial compounds against invasive vaginitis
      strains, this study was conducted for fast screening of plant samples. Materials
      and Methods: Thirty Iranian plant samples were successively extracted by n
      hexane, ethyl acetate and methanol to obtain a total of 90 extracts. Each extract
      was prepared in six concentrations and evaluated for antifungal activity via a
      micro-broth dilution method. Further phytochemical study of the aerial parts of
      Plumbago europaea, as the most promising source of anti-Candida compounds (with
      minimum inhibitory concentration of about 7MUg/ml), was carried out and
      antifungal activity in the ethyl acetate extract was tracked using a combination
      of HPLC time-based fractionation and Thin Layer Chromatography-Bioautography via
      a bioassay-guided fractionation procedure. The compounds in the active region of
      the chromatogram were purified by a combination of column chromatography and
      preparative TLC, and then structure elucidation was achieved by 1D and 2D NMR,
      mass spectrometry and UV spectra. Results: Seven compounds were isolated and
      identified: (1) plumbagin, (2) isoplumbagin, (3) 5, 8-dihydroxy-2-methyl-[1, 4]
      naphthoquinone, (4) droserone, (5) 7-methyljuglone, (6) Isozeylanone, and (7)
      methylene-3, 3'-diplumbagin. Antimicrobial activity of the purified compounds
      were also evaluated against C. albicans (MIC values ranging from 2 to 2500 MUM)
      and Gardnerella vaginalis (MIC values ranging from 20 to 2500 MUM). Conclusion:
      These naphthoquinone compounds could be surveyed for finding new and more
      effective anti-vaginitis agents via drug design approaches.

PMID- 30112158
TI  - Enteroviruses and Adenoviruses in stool specimens of paralytic children- can they
      be the cause of paralysis?
AB  - Background and Objectives: Acute flaccid paralysis (AFP) is a complicated
      clinical syndrome with a wide range of potential etiologies. Several infectious
      agents including different virus families have been isolated from AFP cases. In
      most surveys, Non-polio Enteroviruses (NPEVs) have been detected as main
      infectious agents in AFP cases; however, there are also some reports about
      Adenovirus isolation in these patients. In this study, NPEVs and Adenoviruses in
      stool specimens of AFP cases with or without Residual Paralysis (RP) with
      negative results for poliovirus are investigated. Materials and Methods: Nucleic
      acid extractions from 55 AFP cases were examined by nested PCR or semi-nested PCR
      with specific primers to identify NPEVs or Adenoviruses, respectively. VP1 (for
      Enteroviruses) and hexon (for Adenoviruses) gene amplification products were
      sequenced and compared with available sequences in the GenBank. Results: From 55
      fecal (37 RP+ and 18 RP-) specimens, 7 NPEVs (12.7%) (2 cases in RP+) and 7
      Adenoviruses (12.7%) (4 cases in RP+) were identified. Echovirus types 3, 17 and
      30, Coxsackie virus A8, and Enterovirus 80 were among NPEVs and Adenoviruses type
      2 and 41 were also identified. Conclusion: Our finding shows that NPEVs and
      Adenoviruses may be isolated from the acute flaccid paralyses but there is no
      association between the residual paralyses and virus detection.

PMID- 30112159
TI  - Role of TNF alpha, IL-6 and CXCL10 in Dengue disease severity.
AB  - Background and Objectives: Dengue virus infections (Dengue) have become
      increasingly common in Pakistan and can result in case fatalities if not managed
      appropriately. Patients with Dengue virus infection may be asymptomatic or
      present with Dengue fever (DF), Dengue with warning signs (DWS) or severe Dengue
      (SD). Severity in Dengue is coincident with an exacerbated production of
      lymphocyte-induced cytokines and chemokines which are associated with plasma
      leakage. We investigated the association of circulating levels of cytokines such
      as Interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and CXCL-10 in Dengue
      patients with differing severity of disease. Materials and Methods: Dengue
      infection was confirmed by testing for human IgM to the Dengue virus. Dengue
      patients (n=58) and healthy controls (n=33) were recruited. Dengue patients were
      grouped into those with DF (n=39), DWS (n=15) and SD (n=4). Serum IL-6, TNFalpha
      and CXCL10 levels were tested by ELISA. The Mann Whitney U test was used for
      statistical analysis. Results: Circulating levels of TNFalpha (p<=0.001) and
      CXCL10 (p<=0.001) levels were increased in Dengue patients as compared with
      controls. When patients were stratified for disease severity, it was observed
      that CXCL10 was increased in DWS as compared to DF (p=0.046). IL-6 levels were
      increased in patients with SD as compared to those with DWS (p=0.044). TNFalpha
      levels were not found to differ between different groups of Dengue patients.
      Conclusion: Raised CXCL10 and TNFalpha levels were associated with increased
      clinical severity of Dengue infection and probably increased disease progression
      due to excessive inflammation and increased vascular changes in the patients.

PMID- 30112160
TI  - Geographic Variations of Stroke Hospitalization across France: A Diachronic
      Cluster Analysis.
AB  - Background: This study evaluates the clustering of hospitalization rates for
      stroke and compares this clustering with two different time intervals 2009-2010
      and 2012-2013, corresponding to the beginning of the French National Stroke Plan
      2010-2014. In addition, these data will be compared with the deployment of stroke
      units as well as socioeconomic and healthcare characteristics at zip code level.
      Methods: We used the PMSI data from 2009 to 2013, which lists all
      hospitalizations for stroke between 2009 and 2013, identified on the most
      detailed geographic scale allowed by this database. We identify statistically
      significant clusters with high or low rates in the zip code level using the Getis
      Ord statistics. Each of the significant clusters is monitored over time and
      evaluated according to the nearest stroke unit distance and the socioeconomic
      profile. Results: We identified clusters of low and high rate of stroke
      hospitalization (23.7% of all geographic codes). Most of these clusters are
      maintained over time (81%) but we also observed clusters in transition.
      Geographic codes with persistent high rates of stroke hospitalizations were
      mainly rural (78% versus 17%, P < .0001) and had a least favorable socioeconomic
      and healthcare profile. Conclusion: Our study reveals that high-stroke
      hospitalization rates cluster remains the same during our study period. While
      access to the stroke unit has increased overall, it remains low for these
      clusters. The socioeconomic and healthcare profile of these clusters are poor but
      variations were observed. These results are valuable tools to implement more
      targeted strategies to improve stroke care accessibility and reduce geographic
      disparities.

PMID- 30112162
TI  - Presumptive Treatment of Malaria in Ghana: Was It Ever Useful? Evidence from the
      Kassena-Nankana District of Northern Ghana.
AB  - Background: The WHO currently advocates parasitological confirmation of malaria
      before treatment is commenced. However, many arguments have emerged both for and
      against this new position. To contribute to the debate, this secondary data
      analysis was conducted to determine the likelihood of malaria parasitaemia in a
      child presenting with fever, vomiting, or cough in the Kassena-Nankana District.
      Methods: The dataset for this analysis was generated during a study to assess the
      incidence and risk factors for paediatric rotavirus diarrhoea in the Kassena
      Nankana District. Over a two-year period, trained field staff recruited 2086
      subjects with episodes of diarrhoea aged 24 months or below into the study. A
      standard case report form was used to collect data on histories of illness,
      symptoms, vaccination, and anthropometry. Blood smears were tested for malaria
      parasites. The data set generated was obtained, cleaned, and analysed using Epi
      Info version 7.1.1.14 statistical software. Results: Of the 2086 subjects
      recruited, 2078 had blood smears done and 54.0% had malaria parasites. Fever and
      vomiting appeared to be associated with parasitaemia with odds ratios of 1.9 (95%
      CI: 1.5586-2.2370) and 1.2 (95% CI: 1.0352-1.4697), respectively. Cough however
      appeared protective with an odds ratio of 0.8 (95% CI: 0.6910-0.9765). The odds
      of parasitaemia appeared to increase where a child presented with more than one
      symptom. Conclusion: Nearly half (46%) of the subjects in this study presented
      with symptoms but had no malaria. Presumptive treatment of malaria may therefore
      be useful in situations where diagnostic tests are not readily available, its
      routine practice should however not be encouraged.

PMID- 30112161
TI  - Antipleuritic and Vascular Permeability Inhibition of the Ethyl Acetate-Petroleum
      Ether Stem Bark Extract of Maerua angolensis DC (Capparaceae) in Murine.
AB  - Maerua angolensis has been used traditionally in the management of pain,
      arthritis, and rheumatism in Ghana and Nigeria but no scientific evidence is
      currently available to give credence to its folkloric use. The aim of this study
      was therefore to evaluate the anti-inflammatory effects of a stem bark extract of
      Maerua angolensis DC (MAE) in acute inflammatory models. The effects of MAE (30
      300 mg kg-1) on neutrophil infiltration, exudate volume, and endogenous
      antioxidant enzymes in lung tissues and lung morphology were evaluated with the
      carrageenan induced pleurisy model in Sprague Dawley rats. The effects of MAE (30
      300 mg kg-1) on vascular permeability were also evaluated in the acetic acid
      induced vascular permeability in ICR mice. MAE significantly reduced neutrophil
      infiltration, exudate volume, and lung tissue damage in carrageenan induced
      pleurisy. MAE increased the activities of antioxidant enzymes glutathione,
      superoxide dismutase, and catalase in lung tissues. The extract was also able to
      reduce myeloperoxidase activity and lipid peroxidation in lung tissues in
      carrageenan induced rat pleurisy. Vascular permeability was also attenuated by
      the extract with marked reduction of Evans blue dye leakage in acetic acid
      induced permeability assay. The results indicated that Maerua angolensis is
      effective in ameliorating inflammation induced by carrageenan and acetic acid. It
      also has the potential of increasing the activity of endogenous antioxidant
      enzymes.

PMID- 30112163
TI  - 68-Gallium DOTATATE scanning in symptomatic patients with negative anatomic
      imaging but suspected neuroendocrine tumor.
AB  - Aim: The study's aim was to determine the utility of 68-Gallium DOTATATE positron
      emission tomography (PET)-CT scanning in patients with carcinoid-like symptoms
      and negative anatomical imaging. Methods: Retrospective analysis of 22 of 196
      patients with carcinoid-like symptoms and no evidence of primary neuroendocrine
      tumor (NET) based on anatomical imaging and endoscopy who underwent 68-Gallium
      DOTATATE PET-CT as part of a prospective clinical trial. Results: Of the
      biochemically positive patients (n = 11), 18% (n = 2) had additional evidence of
      NETs based on 68-Gallium DOTATATE PET-CT. Of the patients identified by 68
      Gallium DOTATATE PET-CT, 50% (n = 1) had a treatment change and 100% showed
      symptom improvement. Of the biochemically negative patients (n = 11), 68-Gallium
      DOTATATE PET-CT identified NETs in 64% (n = 7). Change in management occurred in
      71% patients, and 57% of patients showed symptom improvement. Conclusion: 68
      Gallium DOTATATE PET-CT imaging is useful in detecting NETs in symptomatic
      patients with negative anatomical imaging and changes the treatments in these
      patients.

PMID- 30112165
TI  - Ondansetron 8 mg and 4 mg with normal saline against post-operative headache and
      nausea/vomiting after spinal anesthesia: a randomized double-blind trial.
AB  - The study aims to evaluate the efficacy of ondansetron in preventing post-spinal
      headache, considering the high prevalence of the headache in pregnant women and
      the common use of the adjuvants for prophylaxis against post-operative nausea and
      vomiting (PONV). This double-blind clinical trial included the 195 patients who
      were referred to Taleghani Hospital (in Arak, Iran) for cesarean section (C/S)
      under spinal anesthesia, and then the subjects were assigned to three equally
      sized groups using block randomization. Participants in the first, second, and
      control groups received 8 mg, 4 mg of ondansetron, and normal saline,
      respectively, 5 minutes before surgery. A final volume of 5 cc was prepared by
      adding normal saline. Participants were examined for headache one week after
      surgery, and then data analysis was performed using SPSS 20. The incidence of
      post-spinal headache was significantly higher in the placebo group than in the
      ondansetron 8-mg and 4-mg groups at 24 hours after surgery (P < 0.010). But, no
      significant difference was observed between two ondansetron groups (P <= 0.05).
      The overall incidence of the headache was generally lower in ondansetron 8-mg
      (26.66% vs. 33.68.05%) and 31.66% in ondansetron 4-mg (P < 0.001). Moreover, the
      PONV incidence was significantly higher in the placebo group than in the other
      two groups at 24 hours (P < 0.001). The hemodynamic variables were same in three
      groups. The ondansetron 8-mg dose can be effective to prevent headache after
      spinal anesthesia for C/S. Moreover, the ondansetron 8-mg and ondansetron 4-mg
      have same effect in control of PONV after spinal anesthesia for C/S.

PMID- 30112166
TI  - Safer employment of nitrous oxide in anesthesia machines-a technical simulation.
AB  - Several incidents of anesthesia-attributed mortality in the past were caused by
      misconnection of gas pipelines resulting in ventilation with pure nitrous oxide.
      A simple safety feature may be to "mark" nitrous oxide with a lower pressure than
      oxygen and room air within the hospital's gas pipeline system. Then, any
      misconnection of gas pipelines could be detected by pressure differences with a
      manometer in the anesthesia machine. To check technical suitability, we tested
      maximum achievable nitrous oxide flows of an anesthesia machine at different
      pressures in the nitrous oxide supply line. Using decreased pressures for nitrous
      oxide compared to oxygen did not result in decreased nitrous oxide flows, as long
      as pressure in the nitrous oxide supply line was >1500 hPa. A concept of
      different pressures for nitrous oxide and oxygen could be used to technically
      differentiate between those two gases, and to avoid potentially fatal
      misconnections.

PMID- 30112164
TI  - Comparing remifentanil, magnesium sulfate, and dexmedetomidine for intraoperative
      hypotension and bleeding and postoperative recovery in endoscopic sinus surgery
      and tympanomastoidectomy.
AB  - The study aimed to compare remifentanil, magnesium sulfate, and dexmedetomidine
      for intraoperative hypotension, bleeding volume, and recovery time in endoscopic
      sinus surgery and tympanomastoidectomy (TM). A double-blind clinical trial
      enrolled the patients undergoing endoscopic nasal sinus surgery and TM at
      Amirkabir Hospital (Arak, Iran), who were randomly assigned into three groups
      dexmedetomidine (DEX), remifentanil (REM), and magnesium sulfate (MgSO4) to which
      we intravenously administered 1 MUg/kg DEX, an intravenous dose of 1 MUg/kg REM,
      and 40 mg/kg of intravenous MgSO4, respectively. The blood loss, blood pressure
      (BP), heart ratio (HR), oxygen saturation (SaO2), and recovery time were
      recorded. Significant differences were found statistically in bleeding rates
      among all groups (P = 0.0001). The least amount of blood loss (very mild
      bleeding) was observed at 82.85% in the DEX group. BP and HR were lower in this
      group than those in the other groups. While recovery score was significantly
      different in the three groups (P = 0.007), the recovery time was the highest in
      the DEX group, while the least in the REM group. Based on the present results
      Dexmedetomidine seems to better prevent from bleeding than the others. Moreover,
      DEX can cause lower BP and HR in subjects with lower propofol administration, but
      the recovery time is longer. This study was registered by IRCT2017021114056N11 in
      Iranian Registry Clinical Center.

PMID- 30112167
TI  - Effects of hydrogen-occluding-silica microparticles on wound repair and cell
      migratory behavior of normal human esophageal epitheliocytes.
AB  - Many conventional studies on molecular hydrogen have not examined cell migration
      ability and the relationship between apoptosis and the cytoskeleton. Here we
      investigated the influence of hydrogen-occluding silica microparticles (H2
      silica) on cell migration motility and changes of the cytoskeleton (F-actin) in
      normal human esophageal epithelial cells (HEEpiCs). As the results, cell
      migration was promoted, and formation of microvilli was activated in the 100 ppm
      (low concentration) scratched group. After performing a wound healing assay,
      cells exhibited migration after 48 hours and 72 hours for both 10 ppm and 100 ppm
      groups, suggesting that the wound-repairing effects could be attributed to the
      antioxidant ability of H2-silica. In scratched groups, high levels of activated
      caspase-3 were relatively expressed and presented a tendency to increase the
      observed Bax/Bcl-2 ratio at more than 300 ppm groups. The above-mentioned results
      show that H2-silica induced apoptosis in HEEpiCs, especially in the scratched
      cells. Toxicity may cause an exaggerated apoptosis. Furthermore, since the ratio
      of fascin/tubulin in the 100, 300, and 600 ppm groups tended to increase in both
      the scratched and the non-scratched control groups, H2-silica was thought to be
      able to promote fascin action on normal cells and may be have a proliferative
      effect.

PMID- 30112168
TI  - The role of argon in stroke.
AB  - Stroke, also known as "cerebrovascular accident", is an acute cerebrovascular
      disease that is caused by a sudden rupture of blood vessels in the brain or
      obstruction of the blood supply by blockage of blood vessels, thus including
      hemorrhagic and ischemic strokes. The incidence of ischemic stroke is higher than
      that of hemorrhagic stroke, and accounts for 80% of the total number of strokes.
      However, the mortality rate of hemorrhagic stroke is relatively high. Internal
      carotid artery and vertebral artery occlusion and stenosis can cause ischemic
      stroke, and especially males over 40 years of age are at a high risk of
      morbidity. According to the survey, stroke in urban and rural areas has become
      the first cause of death in China. It is also the leading cause of disability in
      Chinese adults. In a word, stroke is characterized by high morbidity, high
      mortality and high disability rates. Studies have shown that many noble gases
      have the neuroprotective effects. For example, xenon has been extensively studied
      in various animal models of neurological injury including stroke, hypoxic
      ischemic encephalopathy. Compared to xenon, Argon, as a noble gas, is abundant,
      cheap and widely applicable, and has been also demonstrated to be neuroprotective
      in many research studies. In a variety of models, ranging from oxygen-glucose
      deprivation in cell culture to complex models of mid-cerebral artery occlusion,
      subarachnoid hemorrhage or retinal ischemia-reperfusion injury in animals. Argon
      administration after individual injury demonstrated favorable effects,
      particularly increased cell survival and even improved neuronal function.
      Therefore the neuroprotective effects of argon may be of possible clinical use
      for opening a potential therapeutic window in stroke. It is important to
      illuminate the mechanisms of argon in nerve function and to explore the best use
      of this gas in stroke treatment.

PMID- 30112169
TI  - Ozone therapy in conjunction with oral antibiotics as a successful primary and
      sole treatment for chronic septic prosthetic joint: review and case report.
AB  - The world is facing crisis in management of infectious diseases. The mainstay of
      treatment has been chemical anti-infectives. These drugs are failing, as
      superbugs emerge and medicine becomes more sophisticated with treatments such as
      prosthetic devices, which can harbor bacteria protected by biofilm. This case
      report describes a 68-year-old woman who received bilateral artificial hips on
      October 27, 2015. The right hip prosthesis subsequently became septic by June
      2016. Three orthopedic surgeons offered her a several month program, which
      included removal of the prosthesis, implantation of an antibiotic impregnated
      "spacer" and months of intravenous antibiotics. Instead, she sought and received
      intravenous ozone therapy, local joint ozone gas injection, and nutritional
      supplements. She quickly improved. Subsequently, she was given oral Augmentin
      (875 mg three times daily) beginning at September 19, 2016 for 1 month, when a
      third culture returned positive for two oral organisms. She experienced even more
      rapid improvement. By October 12, she reported total resolution of symptoms. A
      subsequent MRI on November 30, 2016 showed total clearance of infection. This is
      the first report of a septic prosthetic joint infection completely resolving
      without some form of surgical intervention, debridement at the least. It is also
      the first to report such cure without the use of any parenteral antibiotics. This
      case and world literature suggest that ozone therapy could be considered as a
      useful adjunctive treatment for hard to treat infection and biofilm.

PMID- 30112170
TI  - Clinical utility of hyperbaric oxygen therapy in dentistry.

PMID- 30101006
TI  - An end to end workflow for differential gene expression using Affymetrix
      microarrays.
AB  - In this article, we walk through an end-to-end Affymetrix microarray differential
      expression workflow using Bioconductor packages. This workflow is directly
      applicable to current "Gene'' type arrays, e.g.the HuGene or MoGene arrays, but
      can easily be adapted to similar platforms. The data analyzed here is a typical
      clinical microarray data set that compares inflamed and non-inflamed colon tissue
      in two disease subtypes. For each disease, the differential gene expression
      between inflamed- and non-inflamed colon tissue was analyzed. We will start from
      the raw data CEL files, show how to import them into a Bioconductor
      ExpressionSet, perform quality control and normalization and finally differential
      gene expression (DE) analysis, followed by some enrichment analysis.

PMID- 30112172
TI  - Synthesis and characterization of Mn/Co/Ti LDH and its utilization as a
      photocatalyst in visible light assisted degradation of aqueous Rhodamine B.
AB  - Luminescent Mn/Co/Ti LDH, synthesized by a single step hydrothermal route, has
      been found to be optically responsive for utilization as a highly efficient
      photocatalyst in destruction of the cationic dye Rhodamine B, in aqueous solution
      under visible light irradiation. The material has been found to be better than
      the commercial catalysts like MnO, CoO, TiO2 and Degussa P25. Multiple techniques
      like XRD, XPS, FT-IR, EIS, TG, UV-visible DRS, PL, TRES, N2-sorption-desorption,
      dynamic light scattering, TEM-EDS and AFM analyses were used to characterize the
      LDH. The results indicated Mn/Co/Ti LDH to have a multilayered crystalline
      structure with hexagonal morphology that carries metal ions in mixed valences,
      oxygen vacancies, defect states, thermal stability, narrow band gap, high surface
      area, and electrostatic surface charge variation with pH. The photocatalytic
      activity of the LDH could be co-related with the structural aspects such as
      oxidation states, narrow band gap, high surface area and existence of defects.
      The active species responsible for photocatalysis have been evaluated with EPR,
      terephthalic acid fluorescence probe and indirect radical-hole trapping
      experiments. The photodegradation mechanism involves electron and hole hopping
      across the material and also photosensitization of the dye. Ex situ 1H-NMR and GC
      MS analyses of the colorless end products of Rhodamine B destruction provide
      further insight into the reaction mechanism. The complete mineralization of the
      decolorized end product of degradation was evaluated with TOC analysis. The
      results indicate the potential for using multi metal incorporated LDH in
      destroying dyes and their degradation products in industrial wastewater.

PMID- 30112173
TI  - Extraskeletal osteosarcoma arising in the subcutaneous tissue of the lower leg: A
      case report and literature review.
AB  - Extraskeletal osteosarcoma (ESOS) is a rare soft tissue sarcoma accounting for 1
      2% of all soft tissue sarcomas. ESOS originating in the superficial (cutaneous
      subcutaneous) tissue is extremely rare, and only 17 cases with subcutaneous ESOS
      have been reported in detail to date. The aim of the present study was to report
      an additional case of subcutaneous ESOS of the lower leg and review previous
      reports of subcutaneous ESOS, focusing on the clinical characteristics, including
      the MIB-1 labeling index, treatment methods and outcomes. A 79-year-old healthy
      man presented with a 3-year history of a painful, slowly growing mass in his
      right lower leg that measured ~5 cm in greatest dimension. Excisional biopsy was
      performed, and ESOS was diagnosed based on the histopathological findings. A wide
      resection was performed when local recurrence developed. Six months after the
      wide resection, lung metastasis was detected. Considering the patient's age,
      stereotactic radiotherapy was performed without chemotherapy. The patient showed
      no evidence of local recurrence or new distant metastases for 2 years after the
      second surgery. We herein present this case of subcutaneous ESOS and review the
      previous 17 reported cases of subcutaneous ESOS. The 5-year survival rate of
      patients with subcutaneous ESOS was 78.6%, which was better compared with that of
      ESOS cases arising in deep soft tissue. Therefore, patients with subcutaneous
      ESOS may have a better prognosis compared with those with deep-seated ESOS,
      although the mean MIB-1 labeling index of subcutaneous ESOS was 24%.

PMID- 30112174
TI  - Successful treatment of a patient with Philadelphia chromosome-positive acute
      lymphoblastic leukemia complicated by bone marrow necrosis and acute renal
      insufficiency: A case report.
AB  - Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL)
      complicated by bone marrow necrosis (BMN) and acute renal insufficiency (ARI) is
      rare in clinical practice. The aim of the present study was to summarize the
      clinical characteristics and treatment methods of a case of Ph+ ALL complicated
      by BMN and ARI. A 23-year-old male patient presented with pyrexia and a 2-month
      history of bone pain, and was diagnosed with Ph+ ALL complicated with BMN and ARI
      on peripheral blood tests, blood biochemistry tests, BM smear and fluorescence in
      situ hybridization. The patient underwent repeated hemodialysis, imatinib
      combination and maintenance chemotherapy, followed by allogeneic hematopoietic
      stem-cell transplantation. Some of the clinical signs and symptoms were
      alleviated, whereas others disappeared, and renal function was restored to
      normal. BM aspiration confirmed absence of necrosis and null lymphoblasts.
      Therefore, timely accurate diagnosis and effective treatment are crucial for
      patients with Ph+ ALL exhibiting potentially fatal complications.

PMID- 30112175
TI  - Oxidative stress marker 8-hydroxyguanosine is more highly expressed in prostate
      cancer than in benign prostatic hyperplasia.
AB  - Oxidative stress is a primary cause of vascular endothelial damage. In the
      prostate, ischemia increases the levels of reactive oxygen species, growth
      factors and cytokines, and induces the development of angiogenesis, which results
      in cancer progression. The expression levels of an oxidative stress marker, 8
      hydroxyguanosine (8-OHdG), were compared between prostate cancer and non
      neoplastic prostate tissues. A prostate tissue microarray composed of 10 cases of
      prostatic adenocarcinoma and 70 cases of benign prostatic hyperplasia was
      immunohistochemically stained for 8-OHdG. All cases expressed 8-OHdG. The levels
      of 8-OHdG expression in prostatic cancer (30.0% moderate and 70.0% strong) were
      significantly higher than those in benign prostatic hyperplasia (71.4% moderate
      and 28.6% strong; (p<0.01). Notably, 8-OHdG is expressed more highly in prostate
      cancer tissues in comparison to benign prostate tissues.

PMID- 30112176
TI  - Aggressive superficial acral fibromyxoma of the great toe: A case report and mini
      review of the literature.
AB  - Superficial acral fibromyxoma is a very rare soft tissue tumor. Fetsch et al
      first described the condition in 2001. It often occurs in the fingers and toes
      and has slow-progressive features. Since being described, a few cases occurring
      in the great toe have been reported. The present study indicated a case of a 37
      year-old male kickboxer with a history of a rapid-growing lump under the nail of
      his left great toe with bone erosion. The patient was suspected to have a soft
      tissue tumor under the nail, such as a glomus tumor, as a differential diagnosis.
      However, a malignant soft tissue tumor as a differential diagnosis could not be
      ruled out because of the observed bone erosion. The patient underwent surgical
      excision, and pathologic analysis revealed superficial acral fibromyxoma. Twenty
      four months after the treatment, he had no complaints or functional disorder and
      no recurrence was noted. Although an unusual diagnosis, surgeons should be aware
      of this tumor, which requires complete surgical excision and follow-up to detect
      recurrence. To the best of our knowledge, this is the first reported case of
      superficial acral fibromyxoma with bone erosion in a great toe.

PMID- 30112177
TI  - Treatment response to osimertinib in a patient with leptomeningeal metastasis
      from lung adenocarcinoma following failure of gefitinib and erlotinib: A case
      report.
AB  - Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are
      effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with
      leptomeningeal metastases (LM); however, a proportion of the patients with
      resistant tumors do not benefit from EGFR-TKI treatment. In the present study the
      case of a female patient with advanced lung adenocarcinoma harboring the EGFR
      L858R mutation (encoded in exon 21) who developed intracranial metastases
      following treatment with erlotinib after gefitinib failure is reported. The
      patient achieved a partial response (PR) after four cycles of chemotherapy with
      pemetrexed/cisplatin. However, after 4 months, LM were detected. The patient was
      treated with osimertinib, a third-generation EGFR-TKI, but the LM continued to
      progress and the patient eventually succumbed to the disease (overall survival, 6
      months). Therefore, LM in patients without the EGFR T790M mutation (encoded in
      exon 20) appear to be resistant to treatment with the third-generation TKI
      osimertinib, which may be associated with human epidermal growth factor receptor
      2 amplification. Further clinical trials are required to confirm our results.

PMID- 30112178
TI  - Giant posterior pararenal schwannoma: A case report and review of literature.
AB  - Schwannomas, arising from Schwann cells of peripheral nerve sheaths, are
      primarily benign tumors. They are rarely found in the retroperitoneal space. To
      date, ~30 cases on giant retroperitoneal schwannomas have been reported. Those
      with a location of pararenal space are even rarer. Clinically, they are often
      misdiagnosed as malignancies. In the present study, a case of a 35-year-old woman
      with a giant schwannoma measuring 13 * 8.5 * 6.5 cm in the posterior pararenal
      space of left retroperitoneum was presented, which was thought to be a malignant
      tumor from the result of computed tomography scan. Later postoperative pathology
      and immunohistochemistry were consistent with benign schwannoma. To the best of
      our knowledge, this was the largest posterior pararenal schwannoma reported in
      literature. It is significant to report this case, and summarize the
      characteristics, diagnosis, treatment and prognosis of the similar cases.
      Furthermore, a brief review of the previously published cases in literature is
      provided.

PMID- 30112179
TI  - Age-related differences in prognosis and prognostic factors among patients with
      epithelial ovarian cancer.
AB  - Approximately 40% of all patients with ovarian cancer in Japan are aged >=65
      years. The aim of the present study was to evaluate the differences in prognosis
      and prognostic factors between elderly and younger patients with epithelial
      ovarian cancer. A total of 114 patients with International Federation of
      Gynecology and Obstetrics (FIGO) stage I-IV ovarian cancer who were initiated on
      primary treatment at the Osaka City University Hospital (Osaka, Japan) were
      included in this study. Patient characteristics, treatment outcome and prognosis
      were compared between elderly (aged >=65 years) and younger patients, and the
      prognostic factors associated with overall survival were evaluated by univariate
      and multivariate analyses. The most common histological type in younger patients
      was clear cell carcinoma (33.8%) vs. serous carcinoma in elderly patients
      (44.1%), with a significant difference in the distribution of histological type
      (P=0.006). Complete resection was achieved in 56.2% of younger patients compared
      with 32.4% of elderly patients (P=0.03). The rates of standard primary treatment
      were comparable (56.7% of younger vs. 50.0% of elderly patients). Overall and
      disease-free survival did not differ significantly between the two groups.
      Multivariate analyses identified FIGO stage and standard primary therapy as
      prognostic factors in younger patients and performance status in elderly
      patients. Age was not an independent significant prognostic factor among patients
      with ovarian cancer. Therefore, performance status, rather than age, should be
      considered when selecting the optimal treatment for elderly patients based on
      objective assessment.

PMID- 30112180
TI  - Effect of ballroom dancing on the well-being of cancer patients: Report of a
      pilot project.
AB  - The present study aimed to evaluate the feasibility of ballroom dancing for
      patients with cancer and their partners, and develop a simple method for
      assessing its effects on the patients' well-being. A total of 11 pairs (14
      patients and 8 healthy partners) participated. Participation was open, and there
      were no restrictions in terms of the type of cancer, treatment or comorbidities.
      An anonymous standardized questionnaire allowing participants to rate their well
      being on a visual analogue scale (VAS) from 1 to 10 was used. This rating was
      repeated at defined time points over 1 week. No adverse events occurred during
      the study, and the teaching methods appeared to be feasible for the patients. The
      well-being of all patients remained stable or increased during the class, and
      returned to the initial level within the following days. A total of 3 patients
      with a low well-being rating prior to class experienced a strong improvement
      during the class, which continued until the last day of observation for 2
      patients. These results confirm the effectiveness of a VAS-based method for the
      evaluation of ballroom dancing in patients with different types of cancer
      undergoing different treatments, and its positive effect on the patients' well
      being.

PMID- 30112183
TI  - Damaging nature of decelerations: Do we adequately prepare players?

PMID- 30112181
TI  - Recreational soccer as sport medicine for middle-aged and older adults: a
      systematic review.
AB  - Background: Strategies to prevent or attenuate the age-related decline in
      physical and physiological function and reduce chronic disease risk factors are
      of clinical importance. Objective: To examine the health benefits of recreational
      soccer in middle-aged and older adults. Design: Systematic review in accordance
      with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      guidelines. Data sources: All available records up until 9 June 2017 in PubMed,
      Web of Science, SPORTDiscus, MEDLINE, Embase, CINAHL Plus, PsycINFO and Cochrane
      Library databases. Eligibility criteria for selecting studies: All randomised
      trials with or without a control group (randomised controlled trials or
      randomised uncontrolled trials) and non-randomised controlled trials that used
      recreational soccer, which includes small-sided soccer games, as the sole or
      principal intervention, and reported relevant effects in untrained/sedentary,
      healthy or unhealthy adults aged 40 years and above were included. Results: Five
      trials described in 13 articles were included, which scored 6-9 out of 12 points
      on the modified Delphi quality rating scale. The duration was from 12 to 52
      weeks, with various frequencies, volumes and game formats performed both outdoors
      and indoors with men and women. The trials indicate that recreational soccer may
      result in improvement in cardiovascular function, body composition and functional
      ability, although no significant changes were observed in postural balance.
      Conclusion: Recreational soccer should be considered an alternative exercise
      modality for untrained, healthy or unhealthy middle-aged and older adults of both
      sexes to maintain an active lifestyle and mitigate a wide array of physical and
      physiological age-related changes.

PMID- 30112182
TI  - Assessment of cardiovascular risk and preparticipation screening protocols in
      masters athletes: the Masters Athlete Screening Study (MASS): a cross-sectional
      study.
AB  - Background: Underlying coronary artery disease (CAD) is the primary cause of
      sudden cardiac death in masters athletes (>35 years). Preparticipation screening
      may detect cardiovascular disease; however, the optimal screening method is
      undefined in this population. The Physical Activity Readiness Questionnaire for
      Everyone (PAR-Q+) and the American Heart Association (AHA) Preparticipation
      Screening Questionnaire are often currently used; however, a more comprehensive
      risk assessment may be required. We sought to ascertain the cardiovascular risk
      and to assess the effectiveness of screening tools in masters athletes. Methods:
      This cross-sectional study performed preparticipation screening on masters
      athletes, which included an ECG, the AHA 14-element recommendations and
      Framingham Risk Score (FRS). If the preparticipation screening was abnormal,
      further evaluations were performed. The effectiveness of the screening tools was
      determined by their positive predictive value (PPV). Results: 798 athletes were
      included in the preparticipation screening analysis (62.7% male, 54.6+/-9.5
      years, range 35-81). The metabolic equivalent task hours per week was 80.8+/
      44.0, and the average physical activity experience was 35.1+/-14.8 years. Sixty
      four per cent underwent additional evaluations. Cardiovascular disease was
      detected in 11.4%, with CAD (7.9%) being the most common diagnosis. High FRS
      (>20%) was seen in 8.5% of the study population. Ten athletes were diagnosed with
      significant CAD; 90% were asymptomatic. A high FRS was most indicative of
      underlying CAD (PPV 38.2%). Conclusion: Masters athletes are not immune to
      elevated cardiovascular risk and cardiovascular disease. Comprehensive
      preparticipation screening including an ECG and FRS can detect cardiovascular
      disease. An exercise stress test should be considered in those with risk factors,
      regardless of fitness level.

PMID- 30112186
TI  - Current methodologies utilized in the conduct of randomized clinical trials.

PMID- 30112185
TI  - Luminal MCF-12A & myoepithelial-like Hs 578Bst cells form bilayered acini similar
      to human breast.
AB  - : The epithelium's functional unit is the bilayered acinus, made of a layer of
      luminal cells, surrounded by a layer of basal cells mainly composed of
      myoepithelial cells. Aim: The aim of this study was to develop a reproducible and
      manipulable 3D co-culture model of the bilayered acinus in vitro to study the
      interactions between the two layers. Materials & methods: Two different
      combinations of cell lines were co-cultured in Matrigel: SCp2 and SCg6 mice
      cells, or MCF-12A and Hs 578Bst human cell lines. Results: Confocal microscopy
      analysis showed that only MCF-12A and Hs 578Bst cells could form some bilayered
      acini. This in vitro bilayered acini model will allow us to understand the role
      of interactions between luminal and myoepithelial cells in the normal breast
      development.

PMID- 30112184
TI  - Circular RNAs as novel biomarkers with regulatory potency in human diseases.
AB  - Circular RNAs (circRNAs) are a large class of noncoding RNAs characterized with
      closed loop structures without 3' and 5' polar ends. They can roughly be divided
      into exonic circRNAs, exon-intron circRNAs and circular intronic RNAs. CircRNAs
      are characterized with stability, prevalence, specificity and conservation, which
      arouse great interest in circRNAs as disease biomarkers. Their abilities to
      sponge to miRNAs, cis-regulate parent genes, bind to proteins and encode proteins
      endow circRNAs a critical role of regulation in eukaryotic cells. This concise
      review focuses on circRNAs as functional biomarkers and therapeutic targets in
      both tumor and nontumorous diseases.

PMID- 30112188
TI  - Recent progress toward antiangiogenesis application of nanomedicine in cancer
      therapy.

PMID- 30112187
TI  - RAB40C regulates RACK1 stability via the ubiquitin-proteasome system.
AB  - Aim: RACK1 is a multifunctional scaffolding protein that is expressed in many
      cellular compartments, orchestrating a number of signaling processes. RACK1 acts
      as a signaling hub to localize active enzymes to discrete locations; therefore
      tight control of RACK1 is vital to cellular homeostasis. Our aim was to identify
      the mechanisms responsible for RACK1 turnover and show that degradation is
      directed by the ubiquitin proteasome system. Results: Using siRNA screening, we
      identified RAB40C as the ubiquitin E3 ligase responsible for ubiquitination of
      RACK1, and that the action of RAB40C in controlling RACK1 levels is crucial to
      both cancer cell growth and migration of T cells. Conclusion: Our data suggest
      that manipulation of RACK1 levels in this way may provide a novel strategy to
      explore RACK1 function.

PMID- 30112189
TI  - Multiple mutations in lipid-A modification pathway & novel fosA variants in
      colistin-resistant Klebsiella pneumoniae.
AB  - Aim: To investigate antimicrobial resistance mechanisms in a cluster of colistin
      resistant Klebsiella pneumoniae. Methods: Antimicrobial susceptibility was tested
      by disk diffusion and broth microdilution. Whole-genome sequencing and genome
      analysis were performed. Results: The eight colistin-resistant K. pneumoniae
      isolates belonged to three different clones (ST11, 14 and 231). The eptA and arnT
      genes from lipid modification pathway had novel (R157S in arnT and Q319R in eptA)
      and rare mutations (V39L, R152H, S260L and A279G in eptA). Several substitutions
      were also identified in mgrB, pmrB, phoP and phoQ genes. The mcr genes were
      absent in all isolates. Isolates had variants from existing classes of fosA gene.
      Conclusion: Complex combination of mutations might have led to colistin
      resistance, which suggests that continuous surveillance of molecular mechanisms
      is required.

PMID- 30112190
TI  - Systematic review of therapy used in relapsed or refractory diffuse large B-cell
      lymphoma and follicular lymphoma.
AB  - To identify real-world evidence on outcomes from therapies for
      relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma
      (FL), we systematically reviewed literature in Medline/Embase for DLBCL/FL
      related articles on real-world results published during January 2012-May 2016.
      Among 33 included articles, therapies included stem cell transplant (SCT) and
      chemotherapy, including experimental regimens. The highest overall survival rates
      were observed for SCT, long considered an optimal strategy following initial
      relapse. Prognoses were inferior among DLBCL patients receiving rituximab-based
      regimens rather than SCT, particularly among studies that exclusively focused on
      those ineligible for SCT due to age or co-morbidity. A lack of viable treatment
      options for DLBCL/FL patients ineligible for SCT after relapse remains a
      significant gap in care.

PMID- 30112191
TI  - Should patients with diabetes be encouraged to integrate social media into their
      care plan?
AB  - Aim: To evaluate the use of social media of individuals with diabetes mellitus
      (DM). Materials & methods: Both web-based and in-clinic surveys were collected
      from individuals with DM. Descriptive and correlation analyses were employed to
      evaluate respondents' diabetes-specific social networking site behaviors.
      Results: Forty-five patients with DM completed the web-based survey and 167, the
      clinic-based survey, of whom only 40 visited diabetes-specific social networking
      sites. Analysis of online survey data indicated that self-reported adherence to
      lifestyle recommendations was significantly correlated (p < 0.01) with visiting
      the sites. Clinic-based survey data found that patients who reported using DM
      specific web sites monitored home glucose values more often and had better
      compliance with insulin administration (both p < 0.05) compared with nonusers.
      Conclusion: This study provides insight into why individuals visit DM-specific
      social networking sites. Certain self-management behaviors may improve as a
      result of visiting these sites. Further work is needed to explore how to leverage
      social media technology to assist patients with the management of DM.

PMID- 30112192
TI  - Use of Laser Speckle Contrast Analysis during pelvic surgery in a uterine
      transplantation model.
AB  - Aim: Uterine transplantation (UTx) is proposed for treatment of uterine factor
      infertility. Our aim was to assess whether Endoscopic Laser Speckle Contrast
      Analysis (eLASCA) could evaluate pelvic blood flow at anastomotic sites required
      for sheep and rabbit UTx. Results/methodology: eLASCA detected blood flow in
      rabbit UTx #7 and #9. In sheep UTx #2, #3 and #5, the results allowed us to
      conclude that blood flow was present in the uterine graft following
      transplantation; and post-UTx, the animal had heart and respiratory rates, and
      oxygen saturation compatible with a normal hemodynamic status. Conclusion: These
      preliminary results establish the potential of Laser Speckle Contrast Analysis as
      noncontact and real-time tool for observation of spatially-resolved blood flow
      from which other parameters can be derived.

PMID- 30112193
TI  - Does Rabbit Antithymocyte Globulin (Thymoglobuline(r)) Have a Role in Avoiding
      Delayed Graft Function in the Modern Era of Kidney Transplantation?
AB  - Delayed graft function (DGF) increases the risk of graft loss by up to 40%, and
      recent developments in kidney donation have increased the risk of its occurrence.
      Lowering the risk of DGF, however, is challenging due to a complicated etiology
      in which ischemia-reperfusion injury (IRI) leads to acute tubular necrosis. Among
      various strategies explored, the choice of induction therapy is one
      consideration. Rabbit antithymocyte globulin (rATG [Thymoglobuline]) has complex
      immunomodulatory effects that are relevant to DGF. In addition to a rapid and
      profound T-cell depletion, rATG inhibits leukocyte migration and adhesion.
      Experimental studies of rATG have demonstrated attenuated IRI-related tissue
      damage in reperfused tissues, consistent with histological evidence from
      transplant recipients. Starting rATG intraoperatively instead of postoperatively
      can improve kidney graft function and reduce the incidence of DGF. rATG is
      effective in preventing acute rejection in kidney transplant recipients at high
      immunological risk, supporting delayed calcineurin inhibitor (CNI) introduction
      which protects the graft from early insults. A reduced rate of DGF has been
      reported with rATG (started intraoperatively) and delayed CNI therapy compared to
      IL-2RA induction with immediate CNI in patients at high immunological risk, but
      not in lower-risk patients. Overall, induction with rATG induction is the
      preferred choice for supporting delayed introduction of CNI therapy to avoid DGF
      in high-risk patients but shows no benefit versus IL-2RA in lower-risk
      individuals. Evidence is growing that intraoperative rATG ameliorates IRI, and it
      seems reasonable to routinely start rATG before reperfusion.

PMID- 30112194
TI  - "CLUPS": A New Culture Medium for the Axenic Growth of Entamoeba histolytica.
AB  - Amebiasis remains a major health problem in Mexico. Therefore, the search for
      better culture media and low-cost diagnostic and therapeutic tools is
      fundamental. We present a new culture medium for Entamoeba histolytica which
      allows the microbe to preserve its virulence factors and ability to induce
      hepatic abscesses in animal models. The novel CLUPS medium is an improved version
      of the PEHPS medium, previously designed in our laboratory. The main difference
      is the substitution of raw beef liver in PEHPS by raw beef lung in the CLUPS
      medium. To compare the performance of three-culture media (traditional TYI-S-33,
      PEHPS, and CLUPS), E. histolytica trophozoites were cultured in quintuplicate,
      followed by the evaluation of phospholipase activity and the induction of liver
      abscesses in golden hamsters. E. histolytica trophozoites grew significantly
      better in CLUPS medium than in TYI-S-33. Likewise, CLUPS-cultured trophozoites
      produced significantly more phospholipases than TYI-S-33-cultured trophozoites.
      Finally, trophozoites grown in any of the three tested media had similar
      potential to induce liver abscesses.

PMID- 30112195
TI  - Sociodemographic Characteristics, Dietary Practices, and Nutritional Status of
      Adults with Hypertension in a Semi-Rural Community in the Eastern Region of
      Ghana.
AB  - Introduction: Hypertension is a major contributor to the global disease burden
      and mortality. Evidence suggests increasing hypertension prevalence in Ghana but
      there is limited public awareness and information on the characteristics of those
      with the disease. Objective: To describe the baseline characteristics of adults
      with hypertension who were randomized to receive either hypertension related
      nutrition education plus hospital-based standard of care or only the standard of
      care (control group) in Asesewa, a semi-rural community in the Eastern Region of
      Ghana. Only baseline data were used in the present analysis. Methods: A cross
      sectional baseline survey was completed for 63 adults with confirmed hypertension
      diagnosis. Data on sociodemographic characteristics and diet were obtained
      through interviews and participants' body mass index (BMI) was computed. Pearson
      chi-square statistic was used to assess differences between those with both
      elevated diastolic blood pressure (DBP) and systolic blood pressure (SBP) and
      those with only elevated SBP. Results: Mean +/- SD age of participants was 54.5+/
      13.8 years. Approximately 71% of participants had both elevated SBP (>140 mmHg)
      and DBP (>90 mmHg) while the remaining 29% had only elevated SBP. The median
      number of times the food groups beneficial to hypertension management were
      consumed in the preceding week to the interview was 1 for green leafy vegetables,
      1 for dairy products, 2 for fruits, and 4 for legumes. The median number of times
      for consuming harmful food groups was 3 for salted fish and 7 times for fats and
      oils. Signifcantly more participants in the age group above 50 than the younger
      participants had elevated SBP (83.3 vs. 16.7:P=0.027) and those with BMI equal to
      or greater than 25 were more likely to have both elevated SBP and DBP (P=0.047).
      Conclusions: Findings from this study have implications for the prevention and
      management of hypertension in this semi-rural population.

PMID- 30112196
TI  - A Theory-Based Self-Care Intervention with the Application of Health Literacy
      Strategies in Patients with High Blood Pressure and Limited Health Literacy: A
      Protocol Study.
AB  - The purpose of this study is to assess the effectiveness of a theory-based self
      care intervention with the application of health literacy strategies in patients
      with high blood pressure and limited health literacy. This is a randomized
      controlled trial, with measurements at baseline and 1 and 3 months follow-up. 100
      patients with high blood pressure and limited health literacy will be randomly
      allocated to either an intervention group or a usual care control group. We will
      mainly establish the intervention model based on the principal health belief
      model components. Patients randomized to the intervention group will receive four
      educational sessions during four weeks. Considering the limited health literacy
      level of the patients of the study, health literacy strategies will be used in
      educational material design for enhancing the quality of the intervention. In
      order to cover these strategies, we will design four standard animated comics and
      fact sheets with illustrations and photos consistent with the health belief model
      constructs and educational sessions' topics. Data will be collected using some
      questionnaires and will be analyzed using the SPSS software. The findings of this
      study may assist with the development of a theoretical model for self-care
      intervention in patients with high blood pressure and limited health literacy.

PMID- 30112197
TI  - Clinical, Socioeconomic, and Psychosocial Factors Associated with Blood Pressure
      Control and Adherence: Results from a Multidisciplinary Cardiovascular National
      Program Providing Universal Coverage in a Developing Country.
AB  - Background: Limited information exists on blood pressure (BP) control factors and
      adherence to antihypertensive drug therapy (Rx) in developing countries. Methods:
      Cross-sectional study in randomly selected 992 hypertensive patients under a
      Chilean national comprehensive Cardiovascular Health Program (CVHP). Association
      of education, income, diabetes, obesity, physical activity, psychosocial
      characteristics, smoking, and alcohol abuse with BP control and adherence were
      evaluated by multivariate logistic regression. Results: BP control (<140/90 mmHg)
      was achieved in 63.1% of patients, with 38.4% adherent to Rx. Uncontrolled BP
      significantly associated with male sex (OR: 1.73 [95% CI 1.35-2.22]), low family
      income, high emotional-stress-depression score, body mass index, no adherence
      (OR: 1.83 [95% CI 1.44 - 2.32]), multiple Rx, baseline systolic BP value, and
      sedentary life style. Males (OR: 1.54 [95% CI 1.23 - 1.93]), low family income,
      high emotional stress-depression score (OR: 2.15 [95% CI 1.68 - 2.76]), low
      social support, and uncontrolled BP (OR: 1.52 [95% CI 1.22-1.90]) associated with
      no adherence. Conclusions: Comparable BP control (63.1%) to higher-income
      societies was observed. Uncontrolled BP associated significantly to no adherence
      and both to male sex, socioeconomic, and psychosocial factors. Global low
      adherence (38.4%) and improved BP control and adherence in diabetics were noted.

PMID- 30112199
TI  - Prevalence and Risk Factors for Antenatal Depression in Ethiopia: Systematic
      Review.
AB  - Introduction: Antenatal depression is a syndrome, in which women experience
      depressed mood, excessive anxiety, insomnia, and change in weight during the
      period of pregnancy. Maternal depression negatively influences child outcomes and
      maternal health. Antenatal depression was measured by different rating scales,
      namely, BDI, EPDS, and PHQ. The objective of this systematic review was to
      synthesize logical evidence about the prevalence and potential risk factors of
      antenatal depression in Ethiopia. Methods: Our team explored multiple databases
      including PSYCHINFO, MEDLINE, Embase, Google Scholar, and Google Search to detect
      studies published with data on the prevalence of antenatal depression. We found
      246 research papers on antenatal depression, of which 210 did not correspond to
      the title and 27 were duplicates. Subsequently, nine articles were used for
      synthesis prevalence, of which four studies were selected in the analysis of the
      effect of unplanned pregnancy on antenatal depression. Figures were extracted
      from published reports and grey literature, and any lost information was
      requested from investigators. Estimates were pooled using random-effects meta
      analyses. Results: The pooled prevalence of antenatal depression for five studies
      selected, which had used BDI, was 25.33 (20.74, 29.92). The other four studies
      that had included other screening tools (3 EPDS and 1 PHQ) had the prevalence
      decreased to 23.56 (19.04, 28.07), and the pooled effect of unplanned pregnancy
      on antenatal depression was 1.93 (1.81, 2.06). Factors such as age, marital
      status, income, occupation, history of the previous mental disorder, antenatal
      follow-up, unplanned pregnancy, complication during to pregnancy, age of mother
      during pregnancy, conflict, and social support were associated with antenatal
      depression. Conclusions: Antenatal depression is a common maternal problem;
      further attention should be given to the effect of unplanned pregnancy, social
      support, pregnancy-related complications, family conflicts, and violence on
      pregnant women. All these are possible risk factors for antenatal depression.

PMID- 30112200
TI  - Risk Factors for Postoperative Complications among the Elderly after Plastic
      Surgery Procedures Performed under General Anesthesia.
AB  - Background: The frequency of surgery involving elderly patients has been
      increasing. The use of free tissue transfers in the elderly has been examined
      previously (Howard et al., 2005, Hwang et al., 2016, Grammatica et al., 2015,
      Serletti et al., 2000, and Sierakowski et al., 2017), whereas there have not been
      any such studies of plastic surgery procedures. We evaluated the risk factors for
      complications after plastic surgery procedures performed under general anesthesia
      in patients aged >=75 years. Methods: The cases of patients aged >=75 years who
      underwent plastic surgery procedures under general anesthesia at the Department
      of Plastic and Reconstructive Surgery, National Hospital Organization Nagasaki
      Medical Center, between 2009 and 2016 were reviewed retrospectively. Multiple
      logistic regression analysis was used to identify the risk factors for
      postoperative complications. Results: Two hundred and sixty-three cases were
      reviewed. Complications were seen in 137 patients. Age was not predictive of
      complications. The risk factors included a serum albumin level of <2.8 g/dl (odds
      ratio (OR): 2.96), an operative time of >=120 min (OR: 6.22), and an American
      Society of Anesthesiologists performance status of >=3 (OR: 2.39). Conclusions:
      Age is not contraindication for surgery in the elderly. It is important to assess
      comorbidities and perform surgical procedures as soon as possible to shorten the
      surgical period.

PMID- 30112198
TI  - Burden and Determinants of Anemia in a Rural Population in South India: A Cross
      Sectional Study.
AB  - Background/Objectives: To determine the prevalence and determinants of blood
      haemoglobin level and mild, moderate, and severe anemia in a sample of adults
      from rural Tamil Nadu, India. Subjects/Methods: We recruited a sample of men and
      nonpregnant women aged 20 years and older. Clinical health measures included
      blood haemoglobin concentration and body mass index. We assessed associations
      between anemia outcomes and sociodemographic and dietary factors using linear and
      logistic regression modeling. Results: A total of 753 individuals (412 women and
      341 men) participated in this study. The prevalence of anemia was 57.2% among
      women and 39.3% among men (P<0.001). Prevalence of anemia increased with age
      among men (P<0.001) but not women (P>0.05). Iron intake was low; 11.7% women and
      24.1% of men reported iron intakes above recommended dietary allowances
      (P<0.001). Factors (OR (95% CI)) associated with mild or moderate anemia among
      women included television ownership (0.27 (0.13, 0.58)), livestock ownership
      (0.46 (0.28, 0.75)), refined grain consumption (1.32 (1.02, 1.72)), meat
      consumption (0.84 (0.71, 0.99)), and commercial agriculture production (mild: 4.6
      (1.1, 18.8); moderate: 6.8 (1.98, 23.1)). Factors associated with mild, moderate,
      or severe anemia among men included rurality (0.50 (0.25, 0.99)), sugar
      consumption (1.04 (1.01, 1.06)), egg consumption (0.80 (0.65, 0.99)), and high
      caste (7.3 (1.02, 52.3)). Conclusion: Both women and men in this region may be
      particularly vulnerable to anemia, and future research must expand beyond dietary
      risk factors to examine the impacts of sociodemographic and environmental
      factors.

PMID- 30112201
TI  - Burn Pain Management at Burn Unit of Yekatit 12 Hospitals, Addis Ababa.
AB  - Background: Burn pain is a unique and complex challenge for all health
      professionals and the patients. The only way to insure quality burn pain relief
      is the patient's self-report. Thus, assessment of severity of pain and its
      associated factors are important in treatment plan. Objective: To assess severity
      of burn pain and associated factors in Yekatit 12 Hospitals burn unit from
      January 1, 2017, to March 30, 2017. Methods: Hospital based cross sectional study
      design was conducted. Data was collected by using structural questionnaires from
      all eligible patients, those admitted to burn unit of Yekatit 12 Hospital during
      the study period. Severity of burn pain was assessed by using numerical, facial,
      and behavioral pain scale measurement tools. Pain assessment scale was deployed
      for patients by data collectors before medication and dressing change.
      Multivariate logistic regression analysis was conducted to identify significant
      predictors based on p value less than 0.05 with 95% confidence interval. Results:
      A total of 62 burn patients were included in the study. 87.1% of the patients
      feel severe pain and 12.9% of the patients feel moderate pain. Pediatrics age
      groups were about 11 times more likely to feel severe pain than adults, and
      patients with TBSA >= 25% were about 8 times more likely to feel severe burn pain
      than those with TBSA < 25% [AOR = 7.773; CI 1.184, 51.043] (P = 0.033).
      Conclusion and Recommendation: Majorities of burn patients had severe pain and
      burn pain was not appropriately treated. Therefore, appropriate pain management
      was strongly recommended.

PMID- 30112203
TI  - Liposome Bupivacaine Compared to Plain Local Anesthetics to Reduce Postsurgical
      Pain: An Updated Meta-Analysis of Randomized Controlled Trials.
AB  - Objective: Peripheral nerve blocks for postoperative analgesia have improved
      block success, but analgesia efficacy has been limited by the short duration of
      traditional local anesthetics. The results of randomized trials comparing
      liposome bupivacaine with conventional local anesthetic formulations (e.g., plain
      bupivacaine and ropivacaine) have generated conflicting results. This study was
      conducted to systematically review the effectiveness of analgesic efficacy of
      liposome bupivacaine infiltration at the surgical site versus plain local
      anesthetic bupivacaine or ropivacaine in patients undergoing surgery. Methods:
      PRISMA statement guidelines were followed. A search of electronic databases
      National Library of Medicine's PubMed database, Cochrane Database of Systematic
      Reviews, Embase, and Google Scholar from January 2012 to September 2017 was
      performed. Among the 1,612 records identified, 9 randomized controlled trials
      involving 779 patients were eligible for data extraction and meta-analysis.
      Results: Liposome bupivacaine did not reduce postsurgical pain at rest compared
      to plain local anesthetics at 24 and 48 hours after surgery. Moreover, liposome
      bupivacaine did not reduce postoperative opioid consumption at 24, 48, or 72
      hours when compared to plain local anesthetics. Liposome bupivacaine did reduce
      postoperative nausea when compared to plain local anesthetics (P =<0.3). There
      was no significant difference in hospital length of stay between study groups,
      the use of plain bupivacaine or ropivacaine, or among orthopedic or nonorthopedic
      procedures. No manifestations of local anesthetic toxicity were reported.
      Conclusions: Our results suggest that liposome bupivacaine does not have an
      analgesic advantage when compared to plain local anesthetics at the surgical site
      for patients undergoing surgical procedures.

PMID- 30112204
TI  - The Effectiveness of Orofacial Pain Therapy in Indonesia: A Cross-Sectional
      Study.
AB  - Objectives: As the most complained oral problems in Indonesia, the therapy of
      orofacial pain has to be constantly evaluated. The objective of the current study
      was to evaluate the effectiveness of orofacial pain therapy in Indonesia.
      Methods: This study recruited 5412 (3816 female; 1596 male) participants from 27
      districts in West Java province. Half of the participants (2714) were recruited
      from those who were treated at community health centers whilst the rest were
      those who were treated at private dental clinics. A Likert-scale questionnaire
      that consists of nine questions that were divided to three subsections was used.
      The first subsection of the questionnaire evaluated the participants' post
      therapy basic oral functions (three questions), and the second part evaluated the
      participants' post-therapy pain intensity and frequency (three questions), whilst
      the last part evaluated the participants' post-therapy activities (three
      questions). All data were then cross-tabulated and correlated by using Spearman
      correlation. Result: The current study revealed that out of 5412 participants,
      4023 (74.33%) participants claimed that the therapy has enabled them to perform
      their work activity as usual, whilst 2576 (59.2%) claimed that the therapy has
      decreased the intensity of the pain moderately. A significant (p < 0.01)
      correlation (r = 0.1) between the type of dental facility visited and the total
      score of the therapy effectiveness was revealed. Conclusion: The therapy of
      orofacial pain in Indonesian sample was proven to be effective. Further study
      evaluating the reasons underlying the current results is of importance.

PMID- 30112202
TI  - Incidence and Health Related Quality of Life of Opioid-Induced Constipation in
      Chronic Noncancer Pain Patients: A Prospective Multicentre Cohort Study.
AB  - Background: High rates of opioid use for chronic noncancer pain (CNCP) have been
      reported worldwide, despite its association with adverse events, inappropriate
      use, and limited analgesic effect. Opioid-induced constipation (OIC) is the most
      prevalent and disabling adverse effect associated with opioid therapy. Our aim
      was to assess the incidence, health related quality of life (HRQOL), and
      disability in OIC patients. Methods: A prospective cohort study was performed,
      with 6 months of follow-up, of adult CNCP patients consecutively admitted in 4
      multidisciplinary pain clinics (MPC). Demographic and clinical data have been
      collected. Brief Pain Inventory (BPI) and Short version of Treatment Outcomes in
      Pain Survey (S-TOPS) were used to measure functional outcomes and HRQOL. OIC was
      assessed using Bowel Function Index (BFI). Results: 694 patients were recruited.
      OIC prevalence at baseline was 25.8%. At 6 months, OIC incidence was 24.8%.
      Female gender (OR = 1.65, p = 0.039), opioid therapy (OR 1.65, p = 0.026), and
      interference pain score on BPI (OR 1.10, p = 0.009) were identified as OIC
      independent predictors. OIC patients presented higher disability and pain
      interference and severity scores. OIC patients reported less satisfaction with
      outcome (p = 0.038). Discussion: Constipation is a common adverse event among
      opioid users with major functional and quality of life impairment. These findings
      emphasise the need of OIC adequate assessment and management.

PMID- 30112205
TI  - Effect of Gravity and Task Specific Training of Elbow Extensors on Upper
      Extremity Function after Stroke.
AB  - Background: In individuals with hemiparetic stroke, reaching with the paretic arm
      can be impaired by abnormal muscle coactivation. Prior trails for improving upper
      extremity functions after stroke have underestimated the role of gravitational
      force in motor planning and execution. Objective: The aims this trial were to
      study the effect of gravity as a facilitator for elbow extension and to estimate
      the immediate and retention effects of task specific training of elbow extensors
      on upper extremity function after stroke. Methods: Twenty-six right handed
      patients with first ever stroke represented the sample of the study. The
      participants were randomly assigned into two equal groups. The study group
      received treatment through two phases. Phase one included training for the elbow
      extensors in an antigravity position. Phase two included a set of task specific
      exercise for 16 weeks. The control group received traditional passive stretch and
      range of motion exercises. Manual dexterity and upper limb function were assessed
      by Nine-Hole Peg Test and Fugl-Meyer upper extremity. Goniometry was used for
      measuring elbow extension and forearm supination active ranges of motion.
      Results: Significant improvements were observed in Nine-Hole Peg Test, Fugl-Meyer
      upper extremity, and ranges of motion at postintervention and follow-up compared
      to preintervention at P<=0.05. Conclusions: The results of this study provide an
      evidence that antigravity positions can be used as a centrally presented
      facilitator of elbow extension. Additionally, task specific training was
      effective in improving upper extremity function and elbow extension range of
      motion.

PMID- 30112207
TI  - Applications of Click Chemistry in the Development of HIV Protease Inhibitors.
AB  - Acquired Immunodeficiency Syndrome (AIDS) has been devastating for millions of
      people around the world. Inhibition of the human immunodeficiency virus (HIV)
      protease is among the most important approaches for the therapeutic intervention
      in HIV infection. Since the discovery of the HIV-1 protease, this enzyme has been
      considered as a key target for the inhibition of viral replication. A large body
      of research has been done to develop an effective HIV-1 protease inhibitor. There
      are to date 10 HIV-1 protease inhibitor drugs approved by the Food and Drug
      Administration (FDA) that have improved the survival and quality of life of HIV
      infected people. These drugs are prescribed in combination with the reverse
      transcriptase inhibitors, which is referred to as highly active antiretroviral
      therapy (HAART). The HIV-1 protease inhibitors play a vital role in HAART. The
      applications of click chemistry are dispersing in the field of drug discovery.
      Recently, click chemistry has captured a lot of attention and has become a
      powerful tool for the synthesis of medicinal skeletons in the discovery of anti
      HIV drugs. Click reaction is a well-known method for making carbon-heteroatom
      carbon bonds. Click reactions are popular because they are wide in scope, of high
      yielding, quick to perform, and easy to purify. In this review, we outlined
      current approaches towards the development of HIV-1 protease inhibitors employing
      click chemistry.

PMID- 30112208
TI  - Clinical Presentation, Outcomes, and Treatment of Membranous Nephropathy after
      Transplantation.
AB  - There are scarce data about clinical presentation and outcomes of posttransplant
      membranous nephropathy (MN), and few reports include a large number of patients.
      This was a retrospective cohort including adult patients with posttransplant MN
      transplanted between 1983 and 2015 in a single center (n=41). Only patients with
      histological diagnosis of MN in kidney grafts were included. Clinical and
      laboratory presentation, histological findings, treatment, and outcomes were
      detailed. Patients were predominantly male (58.5%), with a mean age of 49.4 +/-
      13.2 years; 15 were considered as recurrent primary MN; 3 were class V lupus
      nephritis; 14 were considered as de novo cases, 7 secondary and 7 primary MN; and
      9 cases were considered primary but it was not possible to distinguish between de
      novo MN and recurrence. Main clinical presentations were proteinuria (75.6%) and
      graft dysfunction (34.1%). Most patients with primary recurrent and de novo
      primary MN were submitted to changes in maintenance immunosuppressive regimen,
      but no standard strategy was identified; 31 patients presented partial or
      complete remission, and glomerulopathy appeared not to impact graft and patient
      survival.

PMID- 30112210
TI  - The Factors Affecting Survival in Geriatric Hemodialysis Patients.
AB  - Introduction: The number of geriatric patients is increasing in hemodialysis
      population over the years and mortality is higher in this group of patients. This
      study evaluated the factors affecting geriatric hemodialysis patient survival.
      Materials and Methods: This retrospective cohort study enrolled patients
      discharged from our nephrology clinic from 2009 to 2014. Data collected included
      demographics, Eastern Cooperative Oncology Group-Performance Status, vascular
      access type, and metabolic parameters. Comorbidity was quantified using the
      modified Liu comorbidity index. The outcome measure was mortality. Results: The
      study enrolled 99 elderly dialysis patients (42.4% women (n = 42); mean age 75 +/
      7 years). The mean follow-up duration was 19.7 +/- 11 months. The mortality rate
      over the four years was 47.5% (n = 46). The modified Liu comorbidity index score,
      patient age, and Eastern Cooperative Oncology Group-Performance Status were
      significantly related to mortality in univariate and multivariate analyses.
      Conclusion: The present study revealed that comorbidities and low performance
      status at the onset of dialysis had shortened the survival time in the geriatric
      hemodialysis patient group.

PMID- 30112209
TI  - Projecting the Burden of Chronic Kidney Disease in a Developed Country and Its
      Implications on Public Health.
AB  - Background: Chronic Kidney Disease (CKD) is a major public health problem
      worldwide. There is limited literature on a model to project the number of people
      with CKD. This study projects the number of residents with CKD in Singapore by
      2035 using a Markov model. Methods: A Markov model with nine mutually exclusive
      health states was developed according to the clinical course of CKD, based on a
      discrete time interval of 1 year. The model simulated the transition of cohorts
      across different health states from 2007 to 2035 using prevalence, incidence,
      mortality, disease transition, and disease detection rates. Results: From 2007 to
      2035, the number of residents with CKD is projected to increase from 316,521 to
      887,870 and the prevalence from 12.2% to 24.3%. Patients with CKD stages 1-2
      constituted the largest proportion. The proportion of undiagnosed cases will
      decline from 72.1% to 56.4%, resulting from faster progression to higher CKD
      stages and its eventual detection. Conclusion: By 2035, about one-quarter of the
      Singapore residents are expected to have CKD. National policies need to focus on
      primary disease prevention and early disease detection to avoid delayed treatment
      of CKD which eventually leads to end-stage renal disease.

PMID- 30112206
TI  - Biophysical, Biochemical, and Cell Based Approaches Used to Decipher the Role of
      Carbonic Anhydrases in Cancer and to Evaluate the Potency of Targeted Inhibitors.
AB  - Carbonic anhydrases (CAs) are thought to be important for regulating pH in the
      tumor microenvironment. A few of the CA isoforms are upregulated in cancer cells,
      with only limited expression in normal cells. For these reasons, there is
      interest in developing inhibitors that target these tumor-associated CA isoforms,
      with increased efficacy but limited nonspecific cytotoxicity. Here we present
      some of the biophysical, biochemical, and cell based techniques and approaches
      that can be used to evaluate the potency of CA targeted inhibitors and decipher
      the role of CAs in tumorigenesis, cancer progression, and metastatic processes.
      These techniques include esterase activity assays, stop flow kinetics, and mass
      inlet mass spectroscopy (MIMS), all of which measure enzymatic activity of
      purified protein, in the presence or absence of inhibitors. Also discussed is the
      application of X-ray crystallography and Cryo-EM as well as other structure-based
      techniques and thermal shift assays to the studies of CA structure and function.
      Further, large-scale genomic and proteomic analytical methods, as well as cell
      based techniques like those that measure cell growth, apoptosis, clonogenicity,
      and cell migration and invasion, are discussed. We conclude by reviewing
      approaches that test the metastatic potential of CAs and how the aforementioned
      techniques have contributed to the field of CA cancer research.

PMID- 30112211
TI  - Maternal and Neonatal Characteristics for Late Foetal Death in Latvia between
      2001 and 2014: Population-Based Study.
AB  - Introduction: Stillbirth is one of the most common adverse pregnancy outcomes
      worldwide. Late foetal death (LFD) rates are mostly used for international
      comparisons because of the large variations in stillbirth rates between
      countries. Objective: To examine trends in LFD (including antepartum and
      intrapartum) by multiple births, birth weight, and maternal age in two time
      periods. Methods: A retrospective cohort study was used to analyse data from the
      Medical Birth Register (2001-2014), divided into 2 periods of 7 years each. In
      total, data on 1,340 singletons were analysed. This study calculated LFD rates
      and rate ratios (RR). Results: The overall LFD rate showed a slight statistically
      significant reduction (p < 0.001) of 18% between 2001-2007 and 2008-2014. There
      was a slight increase in the mortality rate from multiple pregnancies (RR
      1.1/1000; 95% CI 0.6-1.9). There were no major differences in the LFD rate by
      maternal age during the time periods. Conclusions: LFD decreased (RR 0.8/1000
      births), as well as intrapartum LFD (RR 0.6/1000 births). Older maternal age
      influenced pregnancy outcomes, and higher LFD rates were observed in the age
      group >=35 years. Substantial intrapartum stillbirths rates indicate problems
      with quality of intrapartum care and emergency obstetric care. Further research
      is needed to evaluate the strategies necessary to substantially reduce the number
      of stillbirths in the country.

PMID- 30112212
TI  - Clinical Arterial Peripheral Vascular Pathology Does Not Impact Short- or Long
      Term Survival after Transcatheter Aortic Valve Replacement.
AB  - Introduction: The dramatic changes in vascular hemodynamics after transcatheter
      aortic valve replacement (TAVR) are well noted. However, little postprocedural
      data exists on the outcomes in patients with clinical arterial peripheral
      vascular pathology [abdominal aortic aneurysm (AAA), carotid artery stenosis
      (CAS), and peripheral artery disease (PAD)] undergoing TAVR for severe aortic
      stenosis. Setting: A single center healthcare system. Methodology: A
      retrospective chart review case-control study of 342 consecutive patients who
      underwent a TAVR for severe aortic stenosis at Sanford Health in Fargo; ND was
      performed to determine if preprocedural comorbid AAA, CAS, or PAD was associated
      with worse outcomes after TAVR. Results: Patients with preprocedural comorbid
      AAA, CAS, or PAD had no significant difference overall survival at 1 month (94%
      versus 95% p =.812), 6 months (88% versus 89% p = .847), 1 year (74% versus 83%,
      p =.130), or 2 years (58% versus 63%, p =.611) after TAVR. Patients with clinical
      arterial peripheral vascular pathology also had no significant difference in
      preprocedural outcomes. Conclusion: This study gives evidence to suggest that
      patients with a comorbid clinical peripheral arterial pathology at the time of
      TAVR do not have a statistically significant increase in mortality out to 2 years
      after TAVR and no increase in procedural complications. These results affirm the
      safety and feasibility of TAVR in patients with AAA, CAS, and/or PAD.

PMID- 30112213
TI  - Sentry Bioconvertible Inferior Vena Cava Filter: Study of Stages of Incorporation
      in an Experimental Ovine Model.
AB  - The Sentry inferior vena cava (IVC) filter is designed to provide temporary
      protection from pulmonary embolism (PE) and then bioconvert to become
      incorporated in the vessel wall, leaving a patent IVC lumen. Objective. To
      evaluate the performance and stages of incorporation of the Sentry IVC filter in
      an ovine model. Methods. Twenty-four bioconvertible devices and 1 control
      retrievable filter were implanted in the infrarenal IVC of 25 sheep, with
      extensive daily monitoring and intensive imaging. Vessels and devices were
      analyzed at early (<=98 days, n = 10) and late (180 +/- 30 days, n = 14 study
      devices, 1 control) termination and necropsy time-points. Results. Deployment
      success was 100% with all devices confirmed in filtering configuration, there
      were no filter-related complications, and bioconversion was 100% at termination
      with vessels widely patent. By 98 days for all early-incorporation analysis
      animals, the stabilizing cylindrical part of the Sentry frame was incorporated in
      the vessel wall, and the filter arms were retracted. By 180 days for all late
      incorporation analysis animals, the filter arms as well as frames were stably
      incorporated. Conclusions. Through 180 days, there were no filter-related
      complications, and the study devices were all bioconverted and stably
      incorporated, leaving all IVCs patent.

PMID- 30112214
TI  - The Effect of a Mechanical Compression Device and Supraglottic Airway on Flow
      Time: A Simulation Study of Out-of-Hospital Cardiac Arrest in a High-Rise
      Building.
AB  - High-rise buildings present unique challenges to providing high-quality CPR. We
      investigated the effect of using a mechanical compressor and supraglottic airway
      on flow time and CPR quality in simulated cardiac arrests occurring within a high
      rise building. Twelve teams of EMS providers performed CPR according to 4
      scenarios: manual compression and ventilation through bag-valve-mask (MAB) or
      supraglottic airway (MAS); mechanical compression and ventilation through bag
      valve-mask (MEB) or supraglottic airway (MES). Chest compression indices did not
      differ significantly among the groups. The mechanical compression groups had a
      higher flow time fraction from exiting the elevator until the manikin was loaded
      into the ambulance than the manual compression groups. The supraglottic airway
      groups had higher flow time fractions from entering the elevator until the end of
      the scenario than the bag-valve-mask groups. The total flow time fraction was
      lowest in the MAB group and was highest in the MEB group (P < 0.001). In
      simulated cardiac arrest in a high-rise building, the use of a supraglottic
      airway maintained flow time at a level similar to that observed with the use of a
      mechanical compressor. Moreover, the use of a mechanical compressor and a
      supraglottic airway increased the flow time most effectively.

PMID- 30112216
TI  - Practical Consequences Resulting from the Analysis of a 21-Multigene Array in the
      Interdisciplinary Conference of a Breast Cancer Center.
AB  - During the multidisciplinary planning of postoperative therapy after breast
      cancer, borderline cases can arise with no clear rationale for or against
      adjuvant chemotherapy. In 50 hormone- receptor-positive, Her2neu-negative
      carcinomas of the breast with no or only minimal lymph node involvement (max.
      pT1a) we initiated an Oncotype DX(r) multigene assay in addition to the
      evaluation of usual parameters. In the oncology conference a vote for or against
      chemotherapy was taken on the basis of the conventional criteria for decision
      making before the test results were available. The final recommendation was made
      after the multigene test. In 32 breast carcinomas (64%) a low recurrence score
      could be documented, while 26 (32%) showed an intermediate RS and 3 (6%) showed a
      high RS. In most cases the result of the test could validate the choice of
      therapy established using conventional criteria. In 5 cases the initial
      recommendation for adjuvant therapy was revised, and in 3 cases chemotherapy was
      secondarily recommended after evaluation of the test results. Conversely, in some
      cases a low or intermediate risk constellation did not argue against a
      recommendation for adjuvant chemotherapy. Altogether, the results of our study do
      not indicate that a multigene assay should be used as a routine diagnostic tool.
      Instead a thorough compilation and careful analysis of conventional parameters
      for therapeutic decision-making should take precedence, with special emphasis on
      histopathological and immunohistochemical results. In selected cases, however, a
      multigene assay can be a useful tool in the deliberation for or against a
      therapeutic pathway.

PMID- 30112215
TI  - The Bacteriology and Its Virulence Factors in Neonatal Infections: Threats to
      Child Survival Strategies.
AB  - Background: Neonatal infection refers to the infection of the newborn during the
      first twenty-eight days of life. It is one of the causes of infant morbidity and
      mortality worldwide. The aim of the study is to determine the relative
      contribution of the different pathogens to the overall disease burden. It will
      also determine the mechanisms of virulence of these pathogens that cause neonatal
      infections at Chukwuemeka Odumegwu Ojukwu University Teaching Hospital (COOUTH),
      Awka. Methods: Biological samples were collected from 30 neonates admitted at the
      special care baby unit (SCBU) of COOUTH and cultured using selective media and
      nutrient agar. The isolates were identified using microbiological and biochemical
      tests. The antibiogram study was determined using Kirby-Bauer disc diffusion
      method on Mueller Hinton Agar. Several methods previously reported in literature
      were used for the characterization of the virulence factors. Results: From the 30
      blood samples collected, Pseudomonas spp. (19.7%), Escherichia coli (23%),
      Salmonella spp. (24.6%), and Staphylococcus aureus (32.8%) were isolated. Male to
      female ratio of study population was 1.5: 1. The isolates were 100 % resistant to
      ticarcillin, cephalothin, ceftazidime, and cefuroxime but appreciably susceptible
      to only levofloxacin (88.85%). They were moderately susceptible to
      ceftriaxone/sulbactam (39.05%) and azithromycin (26.46%). Common virulence
      factors identified among the isolates (up to 90 %) were hemolysin, biofilm
      formation, and acid resistance. Less common virulence factors were proteases (50
      %), deoxyribonucleases (50 %), enterotoxins (63%), and lipopolysaccharide (70%).
      The virulence factors were found mostly among the S. aureus isolates.
      Conclusions: Pseudomonas spp., Escherichia coli, Salmonella spp., and
      Staphylococcus aureus were implicated in neonatal infections in the center and
      most of them were resistant to conventional antibiotics. The organisms showed
      marked virulence and multidrug resistance properties. Levofloxacin, a
      fluoroquinolone, had superior activity on the isolates compared to other
      antibiotics used in the study.

PMID- 30112217
TI  - Beyond Statins: Emerging Evidence for HDL-Increasing Therapies and Diet in
      Treating Cardiovascular Disease.
AB  - Coronary heart disease continues to be the leading cause of death in the United
      States. Current attempts to treat atherosclerosis and coronary artery disease
      often involve pharmaceutical and surgical treatments. While these treatments are
      successful in managing the pain from coronary heart disease, they do little to
      prevent or stop it. There are a number of clinical strategies that are currently
      being researched to treat atherosclerosis through HDL-increasing therapies. These
      clinical studies have shown positive effects through nutritional intervention,
      exercise, stress reduction, and tobacco and alcohol cessation. These treatment
      options are explored in greater detail, including their potential to halt and
      even reverse atherosclerosis. The results from these recent studies and how they
      relate to the mechanism of reverse cholesterol transport are also critically
      examined. Reverse cholesterol transport is a multistep process resulting in the
      net movement of cholesterol from peripheral tissues back to the liver via the
      plasma. The mechanism of reverse cholesterol transport is also further explored
      in this review.

PMID- 30112218
TI  - Can ACE-I Be a Silent Killer While Normal Renal Functions Falsely Secure Us?
AB  - The current case report represents a warning against serious hyperkalaemia and
      acidosis induced by ACE-I during surgical stress while normal renal function
      could deceive the attending anaesthetist. Arterial gas analysis for follow-up of
      haemoglobin loss accidentally discovered hyperkalaemia and acidosis. Glucose
      insulin and furosemide successfully corrected hyperkalaemia after 25 minutes and
      acidosis after 3 hours. These complications could be explained by a deficient
      steroid stress response to surgery secondary to suppression by ACE-I. Event
      analysis and database search found that ACE-I induced aldosterone deficiency
      aggravated by surgical stress response with an inadequate increase in aldosterone
      secretion due to angiotensin II deficiency as a sequel of ACE-I leading to
      defective secretion of H+ and K+. Furosemide is recommended to secrete H+ and K+
      compensating for aldosterone deficiency in addition to other antihyperkalaemia
      measures. Anaesthetising an ACE-I treated patient requires considering ACE-I as a
      potential cause of hyperkalaemia and acidosis.

PMID- 30112219
TI  - Rapid Brain Death following Cardiac Arrest without Intracranial Pressure Rise and
      Cerebral Circulation Arrest.
AB  - We describe here an unusual case of brain death following cardiac arrest. Brain
      electric activity had totally ceased, allowing the confirmation of brain death,
      despite normal cerebral blood flow (assessed by both transcranial doppler and
      tomodensitometry) and no evidence of intracranial hypertension. In our case, a
      residual electric activity was assessed at admission and lesions worsened on
      imaging during ICU stay, suggesting that part of the neuronal damage occurred
      after brain reperfusion. All these elements suggest BD rather by cellular
      toxicity than intracranial pressure elevation.

PMID- 30112220
TI  - Erythema Dyschromicum Perstans in an 8-Year-Old Indian Child.
AB  - We report an 8-year-old East Indian boy with erythema dyschromicum perstans. The
      condition has very rarely been reported in prepubertal Indian children. A perusal
      of the literature revealed but two cases, to which we add another one.
      Recognition of erythema dyschromicum perstans in prepubertal Indian children is
      important for proper diagnosis and to prevent unnecessary investigations.

PMID- 30112221
TI  - Vitiligo Appearing after Oral Isotretinoin Therapy for Acne.
AB  - Isotretinoin is an effective treatment for severe and scarring acne. In this
      report, we describe a case developing vitiligo after isotretinoin therapy for
      scarring acne. It is not known whether this was a coincidence or might be
      precipitated by the treatment.

PMID- 30112222
TI  - Dasatinib-Induced Hypopigmentation in Pediatric Patient with Chronic Myeloid
      Leukemia: A Case Report and Review of the Literature.
AB  - Dasatinib is an oral second-generation multitarget tyrosine-kinase inhibitor
      (TKI) that is efficacious in treating imatinib-resistant chronic myeloid leukemia
      (CML) or intolerant cases. Noncutaneous adverse effects with dasatinib are well
      known in the literature, most commonly cytopenias and fluid retention, while
      pigmentary abnormalities have rarely been reported. We report the case of a 12
      year-old male known case of CML, who presented to dermatology clinic
      approximately 2 years after initiating dasatinib treatment, with new-onset
      hypopigmentation of his upper limb, upper chest, and both knees of six months'
      duration.

PMID- 30112223
TI  - Comment on "Vertebral Arteriovenous Fistula: An Unwelcome Thrill".

PMID- 30112225
TI  - Extreme and Cyclical Blood Pressure Elevation in a Pheochromocytoma Hypertensive
      Crisis.
AB  - Pheochromocytomas are rare adrenal neoplasms characterized by excess secretion of
      catecholamines. We describe the case of a 65-year-old man, known for
      hypertension, with no family history of hereditary pheochromocytoma syndromes. He
      reported a two-year history of flushing, systolic blood pressure surges to 200
      mmHg, headaches, tremors, and syncope. His initial workup revealed elevated 24h
      urine catecholamines and metanephrines. An adrenal MRI in March 2017 showed a
      large 7.6 cm heterogeneous right adrenal lesion. Given orthostatic hypotension,
      his final preoperative dose was limited to a low dose of terazosin and
      metoprolol. In the operating room, shortly after intubation and Foley insertion,
      his blood pressure rose to 350 mmHg. Surgery was cancelled and he was admitted to
      the intensive care unit, where intravenous phentolamine, nitroprusside, and
      nicardipine were started. His systolic blood pressure would oscillate between 60
      mmHg and 350 mmHg at 2-3 minutes' intervals. After 3 days, he was weaned off
      intravenous medications. His oral medications were uptitrated to high doses of
      phenoxybenzamine, metoprolol, and nifedipine. Three weeks later, he underwent
      successful open right adrenalectomy. This case outlines the importance of
      preoperative preparation of pheochromocytomas and raises the question if
      phenoxybenzamine is the alpha-blocker of choice for larger tumours with
      significant hormonal secretion.

PMID- 30112224
TI  - A Large PROP1 Gene Deletion in a Turkish Pedigree.
AB  - Pituitary-specific paired-like homeodomain transcription factor, PROP1, is
      associated with multiple pituitary hormone deficiency. Alteration of the gene
      encoding the PROP1 may affect somatotropes, thyrotropes, and lactotropes, as well
      as gonadotropes and corticotropes. We performed genetic analysis of PROP1 gene in
      a Turkish pedigree with three siblings who presented with short stature. Parents
      were first degree cousins. Index case, a boy, had somatotrope, gonadotrope,
      thyrotrope, and corticotrope deficiency. However, two elder sisters had
      somatotroph, gonadotroph, and thyrotroph deficiency and no corticotroph
      deficiency. On pituitary magnetic resonance, partial empty sella was detected
      with normal bright spot in all siblings. In genetic analysis, we found a gross
      deletion involving PROP1 coding region. In conclusion, we report three Turkish
      siblings with a gross deletion in PROP1 gene. Interestingly, although little boy
      with combined pituitary hormone deficiency has adrenocorticotropic hormone (ACTH)
      deficiency, his elder sisters with the same gross PROP1 deletion have no ACTH
      deficiency. This finding is in line with the fact that patients with PROP1
      mutations may have different phenotype/genotype correlation.

PMID- 30112226
TI  - A Case of Diabetic Ketoacidosis Presenting with Hypernatremia, Hyperosmolarity,
      and Altered Sensorium.
AB  - Diabetic Ketoacidosis commonly presents with hyponatremia, but hypernatremia is a
      rare entity. We report a unique case of a 50-year-old woman admitted with altered
      sensorium with blood glucose 979 milligrams/deciliter, serum osmolarity 363
      mOsm/kilograms, and serum sodium 144 milliequivalents/liter. Patient was given
      initial bolus of isotonic saline and continued on half isotonic saline for
      correction of hypernatremia along with insulin infusion therapy. Patient was
      successfully treated with intravenous fluids, insulin infusion, and the altered
      sensorium was resolved without any sequelae. This case illustrates a teaching
      point in the use of intravenous fluids for the treatment of Diabetic Ketoacidosis
      with hypernatremia.

PMID- 30112227
TI  - Megestrol Acetate-Induced Symptomatic Hypogonadism in a Male Patient.
AB  - The hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary
      gonadal (HPG) axis are very sensitive and can be affected by external factors
      like stress, starvation, and medication. Medication-induced suppression of these
      axes can cause adrenal insufficiency (AI) and hypogonadism. Exogenous
      glucocorticoid use is the most common cause of iatrogenic AI. Our aim is to bring
      attention to another broadly prescribed medication, megestrol acetate (MA), as
      the cause of suppression of both these axes. We report a case of symptomatic
      hypogonadism and asymptomatic AI in a male patient secondary to MA. The patient
      presented with decrease in testicular size and erectile dysfunction. His total
      testosterone and morning cortisol levels were low, but FH, LH, and TSH were
      normal. His pituitary MRI was unremarkable. Upon discontinuation of MA, the
      patient's testosterone and cortisol levels normalized and his symptoms resolved.
      Hypogonadism and AI are known adverse effects of MA, but symptomatic hypogonadism
      as the primary manifestation has only been reported once in previous literature.
      Prolonged hypogonadism can lead to sarcopenia, depression, and osteoporosis,
      while asymptomatic AI carries the risk of becoming overt AI. Thus, heightened
      awareness of the impact of MA on both these axes is necessary.

PMID- 30112228
TI  - A Case of Diffuse Leptomeningeal Glioneuronal Tumor Misdiagnosed as Chronic
      Tuberculous Meningitis without Brain Biopsy.
AB  - Here we report a rare case of diffuse leptomeningeal glioneuronal tumor (DLGNT)
      in a 62-year-old male patient misdiagnosed as having tuberculous meningitis. Due
      to its rarity and radiologic findings of leptomeningeal enhancement in the basal
      cisterns on magnetic resonance imaging (MRI) similar to tuberculous meningitis,
      DLGNT in this patient was initially diagnosed as communicating hydrocephalus from
      tuberculous meningitis despite absence of laboratory findings of tuberculosis.
      The patient's symptoms and signs promptly improved after a ventriculoperitoneal
      shunting surgery followed by empirical treatment against tuberculosis. Five years
      later, mental confusion and ataxic gait developed in this patient again despite
      well-functioning ventriculoperitoneal shunt. Aggravation of leptomeningeal
      enhancement in the basal cisterns was noted in MRI. An additional course of
      antituberculosis medication with steroid was started without biopsy of the brain.
      Laboratory examinations for tuberculosis were negative again. After four months
      of improvement, his mental confusion, memory impairment, dysphasia, and ataxia
      gradually worsened. A repeated MRI of the brain showed further aggravation of
      leptomeningeal enhancement in the basal cisterns. Biopsy of the brain surface and
      leptomeninges revealed a very rare occurrence of DLGNT. His delayed diagnosis of
      DLGNT might be due to prevalence of tuberculosis in our country, similarity in
      MRI finding of prominent leptomeningeal enhancement in the basal cisterns, and
      extreme rarity of DLGNT in the elderly. DLGLT should be considered in
      differential diagnosis of medical conditions presenting as communicating
      hydrocephalus with prominent leptomeningeal enhancement. A timely histologic
      diagnosis through a leptomeningeal biopsy of the brain and spinal cord in case of
      unusual leptomeningeal enhancement with uncertain laboratory findings is
      essential because cytologic examination of the cerebrospinal fluid in DLGNT is
      known to be negative.

PMID- 30112229
TI  - A Rare Presentation of Invasive Tuberculosis of the Central Nervous System in an
      Immunocompetent Patient in a Nonendemic Country.
AB  - We herein report a rare case of a 25-year-old immunocompetent male patient with
      disseminated tuberculosis of central nervous system (CNS), first presenting as
      multiple cerebral lesions with no meningeal involvement. Subsequent diagnostic
      workup disclosed extensive peritoneal involvement. A broad differential diagnosis
      was considered, including neoplastic and infectious diseases. The diagnosis was
      confirmed with positive PCR result for Mycobacterium tuberculosis in the biopsied
      mesenteric tissue. The patient was started on tuberculostatic regimen with
      favorable outcome. No acquired or hereditary immunodeficiency was documented.
      Disseminated tuberculosis in immunocompetent individuals is extremely rare.
      Genetic susceptibility factors have been reported in individuals with extensive
      forms of the disease and a high index of suspicion is required, as observed in
      our case.

PMID- 30112230
TI  - Extensive Multiple Sclerosis Reactivation after Switching from Fingolimod to
      Rituximab.
AB  - During treatment with fingolimod, B cells are redistributed from blood to
      secondary lymphoid organs, where they are protected from the effect of anti-CD20
      and other cell-depleting therapies. We describe a multiple sclerosis patient who
      had almost complete depletion of B cells in blood during and shortly after
      treatment with fingolimod. He developed severe disease activity resembling immune
      reconstitution syndrome after switching from fingolimod to rituximab, with first
      dose being six weeks after fingolimod cessation. Following recommendations from
      the Swedish MS Association, rituximab treatment was started as one single dose of
      1000 mg. In patients treated with fingolimod, pathogenic B cells may still be
      sequestered in secondary lymph nodes if this dose is given early. To deplete such
      B cells as they egress from the lymph nodes, we propose that a second dose of
      rituximab a few weeks after the first dose should be considered.

PMID- 30112231
TI  - Primary Sphenoidal Sinus Lymphoma with Initial Presentation as Unilateral
      Abducens Nerve Palsy Symptom.
AB  - A 48-year-old man presented with 3 days of mild horizontal diplopia in the left
      direction, followed by the onset of headache 17 days later. A physical
      examination revealed isolated left abducens nerve palsy. Head computed tomography
      (CT) and magnetic resonance imaging (MRI) scans revealed soft-tissue density
      neoplasms that occupied the sphenoidal sinus and further invaded to destroy the
      clivus. Immunohistochemical staining of neoplasms was performed from biopsies
      samples. The pathological diagnosis was extranodal natural killer (NK)/T-cell
      lymphoma (ENKL), nasal type, associated with Epstein-Barr virus (EBV). The
      patient subsequently exhibited secondary symptoms (fever, night sweats), enlarged
      lymph nodes, renal metastases, and hemophagocytic syndrome, with clinical
      diagnosis stage IV of ENKL. The patient has a poor prognosis. This report is
      unique in two aspects: the unilateral abducens nerve palsy as the initial and
      isolated symptom of ENKL, and the primary sphenoidal sinus ENKL.

PMID- 30112232
TI  - Live Birth from the Transfer of a Severely Fragmented Embryo Observed by
      Morphokinetics.
AB  - We report a live birth from a heavily fragmented embryo which continued cleavage
      to a fully expanded blastocyst. A 32-year-old patient underwent 2 IVF cycles
      without achieving pregnancy. In the first cycle, 2 embryos with fragmentation
      were transferred; in the second, all embryos were fragmented and no embryo
      transfer was performed. In a third cycle, 12 oocytes were retrieved and 11 of
      them were fertilized. On day 2, all 11 embryos started to unwind to fragments. By
      careful annotation, using the time-lapse EmbryoScope, we observed that one embryo
      continued division as expected, discarding all fragments aside. On day 5, this
      embryo showed promising annotation according to our lab model. The embryo was
      transferred into the uterus and resulted in the birth of a healthy baby at term.
      To our knowledge, this is the first case report assisted by EmbryoScope where a
      healthy baby was delivered from a fragmented embryo.

PMID- 30112233
TI  - Two Case Reports of Intravenous Leiomyomatosis with Hyaluronan Expression.
AB  - Intravenous leiomyomatosis (IVL) is a rare benign neoplasm. Herein, we describe
      two cases of IVL at different levels of progression. The tumor in Case 1 was
      extensive, invading the right atrium after a hysterectomy for a uterine myoma.
      The tumor temporarily responded to hormonal treatment; however, tumor regrowth
      occurred. In contrast, the tumor in Case 2 extended only to the pelvic veins and
      was revealed preoperatively. Hysterectomy and bilateral salpingo-oophorectomy
      were performed, resulting in the complete surgical resection of the tumor. In
      Case 2, no recurrence has been observed. Tumor samples were evaluated for
      hyaluronan expression using Alcian blue staining (with and without hyaluronidase
      digestion). The tumor in Case 1 stained strongly positive for hyaluronan while
      the tumor in Case 2 stained weakly positive for hyaluronan. In contrast, a large
      non-IVL uterine leiomyoma (control) stained negative for hyaluronan. These
      results suggest a relationship between tumor hyaluronan expression and IVL
      progression, similar to that in other cancers.

PMID- 30112234
TI  - Uterine Tumor Resembling Ovarian Sex-Cord Tumors Initially Diagnosed as a
      Prolapsed Fibroid.
AB  - Background: First described in 1945 by Morehead and Bowman, uterine tumors
      resembling ovarian sex-cord tumors (UTROSCT) are rare tumors of the uterine body
      that tend to occur in menopausal women presenting with abnormal vaginal bleeding,
      abdominal pain, and increased uterine volume. UTROSCT are usually diagnosed from
      incidental histological findings following hysterectomy performed due to a
      suspected endometrial polyp or uterine fibroids. Objective: To report on a 46
      year-old patient with abnormal vaginal bleeding. At physical examination, a
      pediculated nodular lesion was found protruding from the external cervical os.
      Histopathology of the resected lesion led to a diagnosis of UTROSCT. Total
      abdominal hysterectomy with bilateral adnexectomy was then performed. The patient
      is currently undergoing regular outpatient follow-up, with no evidence of disease
      after one year. Methods: Data were retrieved from the patient's records, and
      macroscopic and microscopic images of the tumor were obtained. Discussion:
      Reports of metastasis or recurrence are rare. UTROSCT are considered of uncertain
      malignant potential and no particular form of treatment is formally recommended,
      with hysterectomy currently being the treatment of choice. This patient will be
      followed up for five years during which clinical examination and tomography of
      the chest, abdomen, and pelvis will be performed annually.

PMID- 30112235
TI  - Pelvic Inflammatory Disease: Possible Catches and Correct Management in Young
      Women.
AB  - The incidence of adnexal masses increases exponentially with age and the most
      frequent causes in young women are physiologic cysts and pelvic abscesses with
      pelvic inflammatory disease (PID). Clinical examination can direct physicians to
      an appropriate management of adnexal mass, but the role of transvaginal
      ultrasound is crucial for diagnosis and treatment decision, even if it sometimes
      can be misleading, especially in young women. Ca 125, blood count, and CRP are
      useful to clarify suspected etiology of a pelvic mass, but specificity and
      positive predictive value are low because elevation of laboratory tests may occur
      in several benign conditions. In our work we present four cases of suspected
      pelvic masses. Despite guidelines for management of PID, the right timing to
      switch to surgical therapy is not clear. Therefore, the treatment decision should
      be based on a careful evaluation of various parameters such as signs symptoms and
      above all age. Moreover, we believe that, for a correct diagnosis and for the
      best fertility sparing treatment, it is also extremely important to refer to a
      gynecological oncology unit with an expert surgeon.

PMID- 30112236
TI  - Umbilical Artery Thrombosis with Associated Acute and Severe Fetal Growth
      Restriction and Transient Severe Protein S Deficiency: Report of a Case with
      Prenatal Ultrasound Diagnosis Allowing for Timely Intervention and Good Outcome.
AB  - Background: Thrombosis of one of the umbilical arteries can be associated with
      adverse pregnancy outcomes such as stillbirth and severe intrauterine growth
      restriction (IUGR). Case: A 21-year-old gravida 1 patient, with a history of 3
      vessel cord at 20 weeks, presented at 29 weeks with a single umbilical artery.
      The estimated fetal weight measurements at 26 weeks, 29 weeks, and 31 weeks were
      at the 27th percentile, the 26th percentile, and less than the 5th percentile,
      respectively. At 33 weeks, amniotic fluid index became abnormal at 2.3 cm and
      fetal heart tracing revealed spontaneous prolonged decelerations, and a cesarean
      delivery was performed. Placental pathology showed thrombosis of one of the
      umbilical arteries. At birth, a transient protein S deficiency was detected
      (activity 13%) and resolved at two months of age (activity 66%). The baby had an
      uneventful clinical course since birth. Conclusion: The recognition of reduction
      of umbilical arteries from two to one allowed for timely intervention with good
      outcome in this case. Thrombosis of umbilical vessels may be associated with a
      deficiency in coagulation proteins such as protein S.

PMID- 30112238
TI  - A Rare Malignant Transformation of an Ovarian Cystic Teratoma: A Case Report.
AB  - Mature cystic teratoma (MCT) is the commonest germ cell neoplasm of the ovary but
      malignant transformation is a rare occurrence (1-2%). Of these malignancies
      documented in literature the commonest are squamous cell carcinoma and
      adenocarcinoma. Urothelial carcinomas arising in an MCT are a rare occurrence and
      only 7 cases have been reported in literature. We report a case of an MCT which
      was complicated by the presence of urothelial carcinoma confirmed on
      histopathological examination.

PMID- 30112237
TI  - Management of Pregnancy with Klippel-Trenaunay-Weber Syndrome: A Case Report and
      Review.
AB  - Background: Klippel-Trenaunay-Weber syndrome is a rare neurocutaneous syndrome
      with vascular involvement. Given the rarity of the syndrome, its management in
      pregnancy is based on the outcome of a few case reports and expert opinion. Case
      Summary: The management of a complicated case with its antepartum, intrapartum,
      and postpartum concerns has been addressed in this review. Conclusions: Prenatal
      consults with anesthesia, general surgery, intervention radiology, and internal
      medicine should be arranged, prior to delivery in anticipation of all the
      possible complications. Apart from the pregnancy management, preconceptional
      counselling including the genetics, prognosis, and contraception has an important
      role in patient management.

PMID- 30112239
TI  - Atypical Features Resembling Poorly Differentiated Thyroid Carcinoma Presenting
      Entirely within a Follicular Adenoma.
AB  - Poorly differentiated thyroid carcinoma (PDTC) is rare and is usually widely
      invasive at presentation. Here we present an unusual case with a component
      meeting diagnostic criteria for PDTC by Turin consensus proposal arising within a
      follicular adenoma. A 44-year-old female was found to have an incidental right
      thyroid nodule that was suggestive of follicular neoplasm on FNA. Histological
      examination of hemithyroidectomy revealed an 11 mm focus with insular growth
      pattern, alteration in cell morphology, and high mitotic count meeting criteria
      for PDTC. In addition there were several regions showing trabecular architecture
      with increased mitotic activity but not meeting criteria for PDTC. The literature
      for such cases is sparse but suggests much better prognosis than conventional
      invasive PDTC, although a biological potential for aggressive behaviour may be
      possible.

PMID- 30112240
TI  - A Case of Neuroleptic Malignant Syndrome in a Profoundly Intellectually Disabled
      Patient with Successful Reintroduction of Antipsychotic Therapy with Quetiapine.
AB  - Neuroleptic Malignant Syndrome (NMS) is a rare condition clinically characterized
      by muscle rigidity, hyperthermia, autonomic instability, and acute mental status
      change. NMS is most often associated with use of high-potency first-generation
      antipsychotic medications; though, other neuroleptics have been implicated as
      well. NMS can be fatal with estimated mortality rates as high as 20%. Patients
      experiencing certain severe complications, including renal failure, have been
      associated with mortality as high as 50%, stressing the need for early
      recognition and treatment. Here we present the case of a 54-year-old male that
      initially presented with symptoms suspicious for sepsis, but who eventually
      developed a clinical picture consistent with NMS. We describe the diagnostic and
      treatment process leading to symptom remission. We then discuss our decision to
      reintroduce an atypical antipsychotic agent, quetiapine. This case illustrates
      the importance of early recognition of the signs and symptoms of NMS and the need
      to initiate treatment promptly in order to prevent complications, including
      death. This case also highlights the decision to resume antipsychotic
      pharmacotherapy after adequate resolution of NMS, demonstrating that it can be
      done so safely if started at low doses coupled with intensive monitoring of the
      patient.

PMID- 30112241
TI  - Pulmonary Vein Thrombosis Associated with Metastatic Follicular Thyroid
      Carcinoma: A Case Report and Review.
AB  - Pulmonary vein thrombosis (PVT) mainly occurs following lung transplantation but
      cases associated with thoracic malignancy have also been described. We describe
      here the first case of PVT in an asymptomatic patient with metastatic follicular
      thyroid carcinoma.

PMID- 30112242
TI  - Traumatic Pulmonary Pseudocyst Mimicking a Congenital Cystic Lung Disease.
AB  - Traumatic pulmonary pseudocyst (TPP) is a rare entity that occurs following a
      trauma to the chest. It usually presents as multiple cystic lesions on thoracic
      imaging. It is treated conservatively and tends to completely resolve after few
      months. In the absence of striking signs of trauma such as rib fractures, TPP can
      be mistaken for other cystic lung diseases. We present a case of TPP in a 17-year
      old male who was seen for mild hemoptysis after falling off a cliff. The extent
      of his right lower lobe cystic lesions along with the lack of major signs of
      trauma led to an incorrect diagnosis of congenital pulmonary airway malformation.
      The patient was considered for lobectomy, which he refused. Imaging of the chest
      repeated one and three years later showed complete resolution of the lesions.

PMID- 30112243
TI  - Segmental Arterial Mediolysis of Omental Arteries with Haemoperitoneum: Case
      Report with Embolization of the Left Omental Artery and Brief Review of
      Literature.
AB  - Segmental arterial mediolysis of an omental artery is an exceptionally rare
      condition. A 69-year-old man presented with haemoperitoneum six days after being
      hospitalized due to pneumogenic sepsis. Computed tomography of the abdomen showed
      a short segment dilatation of an omental artery in the left upper abdomen,
      compatible with segmental arterial mediolysis. Angiographic examination revealed
      alterations of omental branches of the right gastroepiploic artery and an
      aneurysm of the left omental artery, both characteristic of segmental arterial
      mediolysis. Embolization of the left omental artery with use of N-butyl-2
      cyanoacrylate was performed. The postinterventional course was uneventful with
      increase of haemoglobin levels and without symptoms of omental infarction.
      Transcatheter embolization in the setting of haemoperitoneum due to segmental
      arterial mediolysis of an omental branch is technically feasible and a valuable
      alternative to emergency operation.

PMID- 30112244
TI  - Appendiceal Intussusception Mimicking Cecal Mass and Fecal Matter: A Report of
      Two Rare Cases.
AB  - Intussusception of the appendix is a relatively rare event that is usually
      asymptomatic but can present similar to other acute and chronic abdominal
      conditions. We present two separate cases of suspected appendiceal
      intussusception mimicking cecal masses. The authors also present a cursory review
      of the limited number of literatures available concerning this entity to help the
      radiologist avoid misdiagnosis and potentially unnecessary invasive intervention.

PMID- 30112245
TI  - Contribution of Imaging in Diagnosis of Primitive Cyst Hydatid in Unusual
      Localization: Pleura-A Report of Two Cases.
AB  - Hydatic disease has always been the most common in countries where large amount
      of sheep and cattle is raised, but increased travel and immigration have made
      this condition a serious worldwide public problem. Cyst hydatid may affect all
      parts of the human body like the heart, the bone marrow, the eye, the brain, the
      kidney, and the spermatic cord. Humans can become infested by accidentally
      ingesting the eggs that are passed in the feces from definitive hosts (usually a
      canid, such as a wolf, fox, or dog). Even in endemic countries, the primitive
      pleural hydatid cyst is exceptional, and it is very difficult to distinguish from
      other pleural and parietal cystic masses especially that in majority of cases the
      immunologic tests are negative. We report two cases of pleural hydatid cyst
      discovered in two young patients, with a nonspecific clinical presentation. The
      interest of this paper is to raise the primordial role of imaging in the positive
      diagnosis of primary pleural hydatid cyst.

PMID- 30112246
TI  - Atypical Neuropsychiatric Presentation in a Patient Expecting Liver
      Transplantation.
AB  - Patients presenting with acute or chronic hepatopathy can develop altered mental
      status with psychomotor slowing, most commonly indicating encephalopathy. We
      present the case of a 56-year-old patient who developed subacute atypical
      neuropsychiatric symptoms including cognitive and behavioural disorganization,
      manic-like state, and lateralized parkinsonian syndrome. The sequence of events,
      complete work-up, and detailed neuropsychiatric examination were not compatible
      with hepatic encephalopathy or delirium; therefore we extended our differential
      diagnosis and suggested the pathophysiological process described below.

PMID- 30112247
TI  - Two Years of Gynecomastia Caused by Leydig Cell Tumor.
AB  - Gynecomastia is a common incidental finding in males that can be caused by
      various benign or malignant diseases. In rare cases, it results from Leydig cell
      tumors, a rare entity accounting for 3% of all testicular neoplasms. Some of them
      are hormonally active but seldom cause symptomatic endocrine disturbance. Here we
      report on a 32-year-old male presenting with gynecomastia which he had already
      been suffering from for two years. Although he had been seen by three other
      specialists, including a urologist, none of them found the small mass in the
      upper pole of his right testis. We decided to perform testis-sparing surgery
      which confirmed the diagnosis of a hormonally active Leydig cell tumor. During
      follow-up, hormonal status normalized, and gynecomastia began to resolve.

PMID- 30112248
TI  - Application of genome analysis strategies in the clinical testing for pediatric
      diseases.
AB  - Next-generation sequencing (NGS) is being used in clinical testing. Government
      authorities in both China and the United States are overseeing the clinical
      application of NGS instruments and reagents. In addition, the US Association for
      Molecular Pathology and the College of American Pathologists have jointly
      released a guidance to standardize the analysis and interpretation of NGS data
      involved in clinical testing. At present, the analysis strategies and pipelines
      for NGS data related to the clinical detection of pediatric disease are similar
      to those used for adult diseases. However, for rare pediatric diseases without
      linkage to known genetic variants, it is currently difficult to detect the
      relevant pathogenic genes using NGS technology. Additionally, it is challenging
      to identify novel pathogenic genes of familial pediatric tumors. Therefore,
      characterization of the pathogenic genes associated with above diseases is
      important for the diagnosis and treatment of rare diseases in children. This
      article introduces the general pipelines for NGS data analyses of diseases and
      elucidates data analysis strategies for the pathogenic genes of rare pediatric
      diseases and familial pediatric tumors.

PMID- 30112249
TI  - Longitudinal associations of lymphocyte subsets with clinical outcomes in chronic
      fatigue syndrome.
AB  - Background: Chronic fatigue syndrome (CFS) is characterized by prolonged fatigue
      and other physical and neurocognitive symptoms. Some studies suggest that CFS is
      accompanied by disruptions in the number and function of various lymphocytes.
      However, it is not clear which lymphocytes might influence CFS symptoms. Purpose:
      To determine if patient reported fatigue symptoms and physical functioning scores
      significantly changed across time with lymphocyte counts as evidence of a
      relation among chronic fatigue symptoms and the immune response. Methods: The
      current longitudinal, naturalistic study assessed the cellular expression of
      three lymphocyte subtypes -- natural killer (NK) cells (CD3-CD16+ and CD3-CD56+)
      and naive T cells (CD4+CD45RA+) -- to determine whether changes in lymphocytes at
      4 time points across 18 months were associated with clinical outcomes, including
      CFS symptoms, physical functioning, and vitality, among patients with chronic
      fatigue.. Latent growth curve models were used to examine the longitudinal
      relationship between lymphocytes and clinical outcomes. Results: Ninety-three
      patients with Fukuda-based CFS and seven with non-CFS fatigue provided study
      data. Results indicated that higher proportions of naive T cells and lower
      proportions of NK cells were associated with worse physical functioning, whereas
      higher proportions of NK cells (CD3-CD16+) and lower proportions of naive T cells
      were associated with fewer CFS symptoms. Conclusion: These findings suggest that
      lymphocytes are modestly related to clinical outcomes over time.

PMID- 30112250
TI  - In Vivo Evaluation of the Limbus Using Anterior Segment Optical Coherence
      Tomography.
AB  - Purposes: To investigate the limbal structure using anterior segment optical
      coherence tomography (AS-OCT) and compare the difference between a Chinese Han
      population and a Caucasian population. Methods: Sixty healthy Chinese Han
      subjects (109 eyes, Chinese group) and 32 healthy Caucasian subjects (51 eyes,
      Caucasian group) were included in this comparative cross-sectional study. The
      central cornea and the superior, inferior, nasal, and temporal limbal regions of
      each subject underwent Fourier-domain AS-OCT. The following parameters were
      measured: corneal epithelial thickness (CET), maximum limbal epithelial thickness
      (LET), the mean LET, the width of limbus, distance between scleral spur and the
      location where limbal epithelium was the thickest (S-T), and limbal epithelial
      area between scleral spur and the end of Bowman's layer (LEA). Results: CET was
      similar in both groups (P = 0.577). The width of limbus was more than 32.8%
      greater in all limbal quadrants in the Caucasian group (range, 1.25-2.20 mm) than
      in the Chinese group (range, 0.81-1.40 mm). S-T and LEA were also significantly
      higher in all limbal quadrants in the Caucasian group (all P < 0.001). The
      maximum LET and mean LET were 7.8% and 6.9% thicker at the nasal limbus and 8.1%
      and 8.7% thicker in the temporal limbus in Caucasian subjects than in Chinese
      subjects. Conclusions: The limbal structures can be visualized using AS-OCT and
      differ significantly between the Caucasian and Chinese eyes. Translational
      Relevance: Research of the limbus and surgeons performing procedures involving
      the limbal area should take into consideration of the anatomic differences
      especially when limbus is used as an anatomic reference.

PMID- 30112252
TI  - Acute Liver Injury Induced by Sitagliptin: Report of Two Cases and Review of
      Literature.
AB  - We present two cases of acute liver injury associated with sitagliptin. The first
      case was a 58-year-old male with a history of poorly controlled type 2 diabetes
      mellitus and hyperlipidemia. Sitagliptin was added for better control of
      diabetes. After initiation of sitagliptin, the patient's serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels increased
      gradually over a period of six months. The second case was a 44-year-old female
      with type 2 diabetes mellitus, and she experienced a more than ten-fold elevation
      in ALT and AST levels after starting sitagliptin therapy. Both patients did not
      have any history of alcohol abuse, acetaminophen use, or chronic liver disease.
      In the literature review, the reported magnitude of liver enzyme derangement with
      sitagliptin is generally mild and transient (two-fold upper limit of normal). We
      believed that the acute derangement of ALT and AST in our patients was due to
      sitagliptin since the ALT and AST normalized shortly after sitagliptin was
      discontinued and remained at baseline after resuming all other medications.
      Further research is needed to understand the mechanism of dipeptidyl peptidase 4
      (DPP-4) inhibitors associated liver injury.

PMID- 30112251
TI  - A Handheld, Colorimetric Optoelectronic Dynamics Analyzer for Measuring Total
      Ammonia of Biological Samples.
AB  - This paper introduces a wireless, solid-state, portable, and automated device
      capable of measuring the total ammonia [ammonia (NH3) and ammonium (NH4+)] levels
      of fluids, including biological samples. This device reliably measures the total
      ammonia of biological samples (e.g., urine) faster than the current ammonia
      quantification techniques. Medical professionals typically estimate NH4+ levels
      using error-prone indirect measurement techniques (i.e., urine anion gap), which
      are time-consuming and are seldom suitable for periodic measurements. Several
      instantaneous measurements of total ammonia levels in a patient urine could be
      utilized as an early warning for both acid-base and/or potassium disturbances.
      Given the device's operation mechanism, it is able to quantify the total ammonia
      concentration within a biological sample in only 5 s and can simultaneously
      transmit data to other devices via Bluetooth. The analytical operation
      demonstrated high sensitivity, high specificity, fast reversibility, rapid
      response time, and has enabled the accurate determination of total ammonia
      concentration in urine samples produced by subjects who had consumed diets of
      variable protein compositions.

PMID- 30112253
TI  - A Rare Case of an Osteolytic Bone-infarct-associated Osteosarcoma: Case Report
      with Radiographic and Histopathologic Correlation, and Literature Review.
AB  - Benign lesions such as Paget's disease of the bone, enchondroma, osteochondromas,
      chronic osteomyelitis/infections and bone infarcts may rarely undergo malignant
      degeneration/transformation into sarcomas. To date, only 14 prior bone infarct
      associated osteosarcomas have been described, with just two being primarily
      osteolytic. We discuss a case of a patient with a humeral bone-infarct, who
      presented with a presumed benign pathological fracture of the humerus through the
      bone infarct. Subsequent imaging and biopsy showed that there was a malignant
      degeneration into a primarily osteolytic osteosarcoma. We review the patient's
      presentation, radiographic and histologic appearance of the osteosarcoma and
      discuss the epidemiology, surgical and non-surgical treatment and surveillance of
      bone-infarct-associated osteosarcomas.

PMID- 30112254
TI  - Fidaxomicin vs Vancomycin for the Treatment of a First Episode of Clostridium
      Difficile Infection: A Meta-analysis and Systematic Review.
AB  - Clostridium difficile infection (CDI) continues to possess a significant disease
      burden in the United States (US) as well as all over the world. Given the
      increase in severity and recurrence rate, the decrease in cure rate, and the fact
      that the virulent ribotype 027 strain remains one of the most commonly identified
      strains in the US, the Infectious Diseases Society of America (IDSA) published a
      clinical practice guideline in February 2018 moving away from metronidazole as
      the first-line treatment for initial CDI and recommending either oral vancomycin
      or fidaxomicin. The aim of this study is to evaluate the clinical data available
      comparing the efficacy of primary treatment of CDI between those two antibiotics.
      We performed a PubMed, PubMed Central, and ScienceDirect database search without
      restriction to regions, publication types, or languages. A comprehensive
      literature search was performed from January 1, 1980 up to March 20, 2018. We
      used the following keywords in different combinations: Clostridium difficile,
      Clostridium difficile infection, CDI, C. diff, C. difficile, fidaxomicin,
      vancomycin, pseudomembranous colitis, and antibiotic-associated colitis. The
      search was limited to human studies. Data were independently extracted by two
      reviewers with disagreements resolved by a third author. We pooled an odds ratio
      (OR) on two primary outcomes: Clinical cure rate and rate of recurrence during
      the follow-up period. The computer search was also supplemented with manual
      searches by the authors of the retrieved review articles and primary studies. The
      search phrase "((Clostridium difficile) AND vancomycin) AND fidaxomicin" had the
      highest yield results. We identified four observational studies with a total of
      2,303 patients with CDI that met our inclusion criteria. Compared with
      vancomycin, fidaxomicin use was associated with a significantly lower recurrence
      of CDI with a pooled OR of 0.47 (95% confidence interval (CI), 0.37 - 0.60, I2 =
      0). On the other hand, there was no significant association of fidaxomicin use
      with CDI cure rate compared to vancomycin with a pooled OR of 1.22 (95% CI, 0.93 
      1.60, I2 = 0). In light of the recently updated clinical practice guidelines by
      the IDSA, our review suggests that fidaxomicin has a more sustained clinical
      response with a statistically significant lower recurrence rate. Although
      fidaxomicin appears to be the better drug with statistical significance, its cost
      effectiveness continues to be an ongoing controversy. More randomized clinical
      trials are needed to shed light on this matter to assess if there is any clinical
      significance in fidaxomicin superiority.

PMID- 30112255
TI  - Atypical Presentation of Cardiac Tamponade as a Cause of Acute Liver Injury: Case
      Report and Review of Literature.
AB  - Pericardial tamponade is a rare cause of acute liver injury due to the
      compressive effects of an effusion resulting in a poor cardiac output which
      ultimately leads to ischemia-induced injury. We present a patient with chronic
      hepatitis C infection and end-stage renal disease who was transferred to our
      center for further evaluation and management of acute liver injury after
      presenting to an outside hospital with left upper quadrant abdominal pain, nausea
      and vomiting. The patient was discovered to have tamponade physiology on
      transthoracic echocardiogram as an underlying cause of his acute liver injury
      despite lack of clinical tamponade features. He required pericardiocentesis which
      eventually led to resolution of the acute liver injury and he was discharged home
      on day twelve after full recovery. We review the existing literature regarding
      the epidemiology, pathophysiology, clinical presentation, diagnosis, and
      treatment of ischemic hepatitis, which is associated with high mortality;
      therefore early recognition and treatment of the underlying cause are paramount.

PMID- 30112256
TI  - A Rare Case of an Azygos Lobe in the Right Lung of a 40-year-old Male.
AB  - The azygos lobe is a rare anatomical variant, most often encountered in the right
      lung. Its etiology is related to a defect of the migration of the azygos vein
      during the embryonic development. Here, we describe a rare case of an azygos lobe
      of the right lung, diagnosed incidentally on a computed tomography (CT) scan in a
      40-year-old male patient who presented with chest pain, shortness of breath, and
      fever. The initial differential diagnosis included acute myocardial infarction,
      aortic dissection, and myocarditis. Chest CT with contrast matter demonstrated a
      peculiar finding in the right lung which was recognized as an azygos vein passing
      through the upper lobe and separating an azygos lobe with its mesoazygos. The
      azygos lobe may be rarely associated with neoplastic processes or spontaneous
      pneumothorax and its differential diagnosis on imaging studies includes various
      conditions. Knowledge of this variation is important to avoid misdiagnosis or
      complications during thoracic surgery.

PMID- 30112257
TI  - Takayasu Arteritis: A Diagnosis Made Using a Multidisciplinary Approach.
AB  - Takayasu arteritis is an idiopathic chronic vasculitis that involves large blood
      vessels, including the aorta and its main branches. This disease presents
      typically as ischemia or aneurysms that could be prevented by timely diagnosis
      and vigilant management. We present here the case of a 19-year-old male who
      presented with a history of visual disturbance, chest pain, dizziness, and a
      feeble pulse.

PMID- 30112258
TI  - An Immature Ten-year Long-standing Case of Ossifying Fibroma.
AB  - Ossifying fibroma is a rare benign bone neoplasm common in middle age, with
      definite female predominance. Here, we describe a case of an ossifying fibroma in
      a 36-year-old female, with a right facial deformity. The lesion had been present
      for almost 10 years. The panoramic image showed a multilocular appearance with
      scattered radiopacities. Advanced imaging revealed an expansile multilocular
      lesion with multiple small radiopaque foci and a few dense radiopaque masses. A
      histopathological examination confirmed the diagnosis. The case represents a non
      aggressive form of an immature ossifying fibroma.

PMID- 30112259
TI  - Gastric Ulcer from the Pressure of a Gastrostomy Tube: A Rare Cause of Upper
      Gastrointestinal Bleeding.
AB  - Gastrostomy tube placement is a well-known procedure for obtaining permanent
      enteral access and providing long-term nutritional support. Although it is
      usually well tolerated, a diverse array of complications can occur. A rare, and
      often unrecognized, complication of gastrostomy tube placement is upper
      gastrointestinal bleeding secondary to a gastric ulcer caused by pressure from a
      gastrostomy tube bumper or balloon. Here, we present a case of an elderly woman
      who experienced hematemesis and bleeding around the gastrostomy site. This report
      should alert healthcare staff that excessive tightening of the gastrostomy tube
      retainer or prolonged traction of the gastrostomy tube can cause pressure
      necrosis manifesting as gastric ulceration.

PMID- 30112260
TI  - Awareness Regarding Pap Smear Among Female University Students of Karachi: A
      Cross-sectional Survey.
AB  - OBJECTIVE: To determine the knowledge and practices regarding Papanicolaou (Pap)
      smear test among female university students of Karachi. METHOD: This cross
      sectional study was carried out among 491 female university students of Karachi.
      Participants were selected by random sampling between the ages of 18 to 30 years;
      from different universities namely Dow University of Health Sciences (DUHS),
      Jinnah Sindh Medical University (JSMU), and Institute of Business administration
      (IBA). Pearson chi-square test and Mann-Whitney U tests were applied as the
      primary statistical methods. RESULTS: Out of 491 participants, three-quarters of
      the participants knew about the Pap smear test. However, only 1.6% had undergone
      the procedure. Age, socioeconomic status (SES), and medical background all had a
      significant relationship with the awareness of Pap smear test. One-third of the
      females in the study blamed lack of knowledge as the major reason for not getting
      a Pap smear while another third blamed the lack of recommendation by health care
      professionals. CONCLUSION:  According to our study, female undergraduate students
      of Karachi have insufficient knowledge and exposure to Pap smear, a screening
      test that could decrease the burden of cervical cancer among the female
      population of our country. Further research is required to assess the severity of
      the problem and consequently strategize to control it.

PMID- 30112261
TI  - Minimally Invasive Decompression and Physiotherapy for Lumbar Spinal Stenosis in
      Geriatric Patients.
AB  - Background Lumbar spinal stenosis (LSS) is the most common indication for spine
      surgery among the geriatric population. Although decompressive surgery is
      effective, older patients do not benefit as much as younger patients, and they
      are frequently excluded from studies assessing postoperative physiotherapy. We
      sought to evaluate the long-term outcomes after surgery when a novel
      postoperative physiotherapy regimen was included. Methods We performed a
      retrospective review of patients with LSS greater than 70 years old who underwent
      lumbar decompressive surgery by the senior author over the past five years. We
      evaluated patients who participated in a novel postoperative physiotherapy
      regimen involving four phases of rehabilitation aimed at progressively
      independent ambulation. The visual analog scale (VAS), lower extremity motor
      strength, and functional independence measure (FIM) were collected preoperatively
      and after physiotherapy to measure outcomes. Results Ten consecutive patients
      with an average age of 83 years (range: 71 - 96) met the inclusion criteria. Nine
      patients underwent minimally invasive laminotomies at L4-L5 and one underwent a
      laminotomy at L3-L4. The average follow-up time was 41.9 months. The preoperative
      mean VAS was 7.35, and at the end of the study, it was 1.7 (p = 0.005). Three of
      the four patients with preoperative motor deficits improved. The median transfer
      and locomotion subscores of the FIM were six preoperatively and increased to
      seven postoperatively. Neither of these improvements was significant. Conclusions
      Patients older than 70 years undergoing decompressive surgery and a novel
      postoperative physiotherapy regimen experienced significant reductions in pain.
      Independence also increased; however, this did not reach statistical
      significance.

PMID- 30112262
TI  - Rhabdomyolysis Associated with Influenza A Virus Infection.
AB  - Influenza A associated with rhabdomyolysis has become more commonly recognized in
      recent years. It requires prompt recognition and treatment in order to prevent
      heme pigment-induced acute kidney injury. Here we report a 50-year-old female
      without a significant past medical history who presented with a one-week history
      of fevers, chills, fatigue, and generalized body aches. She was on no prior
      medication. Laboratory studies were significant for leukocytosis and elevated
      creatinine kinase up to a peak of 28,216 IU/L. Rapid influenza antigen testing
      was positive for influenza A virus. The patient was diagnosed with influenza A
      induced rhabdomyolysis. According to our literature review, we are the first to
      report a case of influenza A-induced rhabdomyolysis in the 2017-2018 flu season.
      This case highlights the importance of considering rhabdomyolysis as a
      manifestation of an influenza infection.

PMID- 30112263
TI  - Massive Pneumoperitoneum Presenting as an Incidental Finding.
AB  - Pneumoperitoneum is often associated with surgical complications or intra
      abdominal sepsis. While commonly deemed a surgical emergency, pneumoperitoneum in
      a minority of cases does not involve a viscus perforation or require urgent
      surgical management; these cases of "spontaneous pneumoperitoneum" can stem from
      a variety of etiologies. We report a case of a 72-year-old African American male
      with a history of metastatic pancreatic adenocarcinoma who presented with new
      onset abdominal distention and an incidentally discovered massive
      pneumoperitoneum with no clear source of perforation on surveillance imaging. His
      exam was non-peritonitic, so no surgical intervention was recommended. He was
      treated with bowel rest, intravenous antibiotics, and hydration. He had a
      relatively benign clinical course with preserved gastrointestinal function and
      had complete resolution of his pneumoperitoneum on imaging two months after
      discharge. This case highlights the importance of considering non-surgical causes
      of pneumoperitoneum, as well as conservative management, when approaching
      patients with otherwise benign abdominal exams.

PMID- 30112264
TI  - Gamma Knife Radiosurgery for Arteriovenous Malformations Using a Four-Dimensional
      Dynamic Volume Computed Tomography Angiography Planning System as an Alternative
      to Traditional Catheter Angiogram.
AB  - Background Gamma knife radiosurgery (GKRS) remains a critical intervention in the
      long-term management of arteriovenous malformations (AVMs). For planning a
      treatment, identification of the nidus is essential, and it is dependent on high
      resolution blood flow imaging, usually in the form of a traditional angiogram.
      The development of dynamic 320-slice computed tomography (CT) angiography has
      offered a noninvasive alternative to intra-arterial fluoroscopic imaging, and it
      is capable of providing equivalent temporal resolution. In this study, we
      describe the feasibility of using four-dimensional CT angiography (4D-CTA) in
      GKRS planning for AVM treatment and a comparative analysis with a traditional
      angiogram. Methods A retrospective review was performed on AVM patients treated
      via GKRS with a 4D-CTA prior to the day of treatment, on the day of treatment, or
      with a day-of-treatment angiogram. Treatment times, along with total times in the
      Leksell(r) coordinate frame G, were obtained from the medical records. The frame
      on time was calculated by subtracting the treatment time from the total time
      starting from application to removal, and the statistical analysis was performed
      across groups using analysis of variance (ANOVA). All treatments were performed
      on the PerfexionTM model with a dynamic flow imaging procured via a 320-slice CT
      scanner or traditional angiography platform. Results Some 27 patients underwent a
      total of 29 GKRS procedures for AVM treatment at our institution between
      September 2011 and January 2017. Mean age at the time of treatment was 35.5 (6
      65) years, and male:female ratio was 5:4. Some 12 patients had 4D-CTA performed
      prior to the day of treatment, eight patients had the same CTA completed after
      frame placement on the day of treatment, while seven patients underwent
      traditional angiography. The mean frame-on times of each group were 190, 336, and
      426 minutes, respectively (p < 0.0001). No procedures were aborted based on the
      image quality. Conclusions 4D-CTA is an effective tool in identifying the AVM
      nidus for GKRS planning. These studies can be performed prior to the day of
      treatment, allowing for a significant reduction in frame-on time and eliminating
      the risk of angiogram complication on the day of GKRS.

PMID- 30112265
TI  - Pharmaceutical Digital Marketing and Its Impact on Healthcare Physicians of
      Pakistan: A National Survey.
AB  - Objective Digital marketing is replacing traditional marketing strategies in the
      pharmaceutical industry. This study evaluated multiple aspects of the use of
      social media by the physicians of Pakistan, the current role of digital marketing
      in the pharmaceutical industry, and its impact on the change in clinical
      practice. Methods This cross-sectional study included physicians working in
      various clinical settings with at least five years of clinical experience. The
      participants were surveyed on social media tools used, knowledge of digital
      marketing tools, and the digital presence of themselves as physicians. We also
      assessed their knowledge of digital marketing by the pharmaceutical industry of
      Pakistan and its potential influence on changes in their clinical practice.
      Results Seven hundred eighteen physicians were included after taking informed
      consent. The mobile application WhatsApp (WhatsApp Inc., Menlo Park, CA) was the
      most frequently used application per week for medical-related purposes.
      Webinars/webcasts had the highest duration of use per week but were attended by
      only a few physicians, followed by mobile applications and informative health
      websites. The most frequently available digital marketing channels were found to
      be WhatsApp (29.94%), informative health websites (26.7%), and mobile
      applications (20.6%). Less frequently available tools were e-detailing (8.1%),
      webinars/webcasts (7.7%), tele-detailing (6.0%), self-directed web-detailing
      (5.2%), and marketing emails (4.2%). However, despite the limited use,
      webinars/webcasts had the strongest influence for changes in clinical practice
      (48%), followed by websites (42%), mobile applications (41%), WhatsApp (37%), and
      self-directed web-detailing (36%). Conclusion Despite limited use, the percentage
      of influence for clinical practice changes was highest for webinars/webcasts
      followed by websites, mobile applications, and WhatsApp. There is potential for
      increased use of digital promotion strategies from Pakistan's pharmaceutical
      sector.

PMID- 30112266
TI  - Association of Nadir Prostate-specific Antigen >0.5 ng/mL after Dose-escalated
      External Beam Radiation with Prostate Cancer-specific Endpoints.
AB  - Objective Prior studies have suggested that prostate-specific antigen (PSA) nadir
      of 0.5 ng/mL is an important surrogate endpoint for prostate cancer-specific and
      all-cause mortality. This study analyzed our well-followed patient cohort to
      assess whether this endpoint was associated with differences in prostate cancer
      specific endpoints in patients receiving dose-escalated radiation. Methods
      Patients with intermediate- or high-risk prostate cancer (>=T2b, or prostate
      specific antigen >10 ng/mL, or Gleason score >=7) who were treated with external
      beam radiation to a minimum dose of 7560 cGy +/- androgen deprivation between
      2003 and 2011 were identified. Biochemical control, distant metastasis-free
      survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival
      (OS) were compared between those who achieved a nadir PSA <=0.5 ng/mL with those
      who did not via Kaplan-Meier analysis. Univariable and multivariable Cox
      regression was performed on all endpoints to assess their impact on OS. Results
      There were 367 patients identified with a median follow-up of 99.5 months. Two
      hundred five patients (55.9%) received androgen deprivation for a median of 24
      months (range 1-81 months). Most patients (n = 308, 83.9%) achieved a nadir PSA
      <=0.5 ng/mL, which was associated with improvement across all endpoints at 10
      years. This included biochemical control (68.0% versus 24.0%, p < 0.001), DMFS
      (89.6% versus 80.8%, p = 0.019), PCSS (91.1% versus 85.7%, p = 0.01), and OS
      (55.7% versus 45.8%, p = 0.048). On multivariable analysis, nadir PSA >0.5 ng/mL
      remained strongly associated with worse outcomes across all endpoints.
      Conclusions Achievement of nadir PSA <=0.5 ng/mL after completion of dose
      escalated radiation therapy was associated with improvement of all prostate
      cancer endpoints.

PMID- 30112267
TI  - Simultaneous Selective Dorsal Rhizotomy and Baclofen Pump Removal Improve
      Ambulation in Patients with Spastic Cerebral Palsy.
AB  - BACKGROUND: Intrathecal baclofen (ITB) administration via an implanted
      programmable pump and selective dorsal rhizotomy (SDR) are both used for the
      treatment of cerebral palsy (CP) spasticity. OBJECTIVE: To examine whether SDR
      can improve ambulation in children who have been receiving ITB therapy for
      spastic cerebral palsy. METHODS: We reviewed 13 patients who received prior ITB
      placement with subsequent simultaneous SDR and ITB removal. Patients also
      completed a follow-up survey to document long-term motor function. RESULTS: In
      our 13-patient cohort, patients received ITB treatment for an average of 4.4
      [Formula: see text] 1.8 years and the mean age of ITB removal/SDR was 12.5
      [Formula: see text] 5.8 years. The follow-up period ranged from 3 to 19 months
      (mean duration: 6.9 [Formula: see text] 5 months). Pre-operatively, all patients
      had Gross Motor Function Classification System (GMFCS) scores between 2 and 4.
      Nine patients were diagnosed with spastic diplegia, two had spastic triplegia and
      two had spastic quadriplegia. SDR and ITB removal led to improved lower limb
      spasticity and ambulation. GMFCS scores remained stable in all patients. One
      patient developed a cerebrospinal fluid (CSF) collection in the abdominal wall
      due to a CSF leak from the baclofen pump site. All 11 patients who completed the
      follow-up survey noted improved motor function. CONCLUSION: This study
      demonstrates that SDR can reduce spasticity and improve mobility after years of
      ITB treatment for spastic cerebral palsy.

PMID- 30112269
TI  - Optic Discs Swelling Procrastinates Wernicke's Encephalopathy Associated with
      Hyperemesis Gravidarum: A Case Report and Review of Literature.
AB  - Wernicke's encephalopathy following severe hyperemesis gravidarum is an uncommon
      clinical entity. We describe a rare manifestation of optic discs swelling in a
      pregnant woman that has caused a diagnostic dilemma. With high index of suspicion
      of clinical manifestations and radiological evidences, a clinical diagnosis of
      Wernicke's encephalopathy was made. Intravenous thiamine therapy was instituted,
      and prompt improvement of clinical signs was observed. The association of optic
      discs swelling and Wernicke's encephalopathy after hyperemesis gravidarum is
      discussed.

PMID- 30112268
TI  - Eosinophilic Myocarditis Demonstrated Using Cardiac Magnetic Resonance Imaging in
      a Patient with Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss
      Disease).
AB  - Eosinophilic granulomatosis with polyangiitis (EGPA), historically known as the
      Churg-Strauss disease, is a small- to medium-sized vessel multi-organ vasculitis
      with a propensity to involve the heart. EGPA is a rare condition with an
      estimated annual incidence of one to 4.2 people per million. The cardiac
      involvement causes significant morbidity and mortality in EGPA patients.
      Approximately 50% of the deaths in EGPA are related to cardiac disease and occur
      within the first few months since diagnosis. The current recommendations support
      evaluation of cardiac involvement by using history, physical exam and
      multimodality imaging including echocardiogram and cardiac magnetic resonance
      imaging (CMR). Here, we report a rare case of eosinophilic myocarditis in a 19
      year-old patient with EGPA seen on CMR. Pertinent literature is also reviewed. We
      highlighted the importance of CMR in diagnosing and follow up of EGPA patients.

PMID- 30112270
TI  - Pigmented (melanotic) diffuse neurofibroma of the back in neurofibromatosis type
      1.
AB  - Neurofibromatosis type 1 (NF1) is a tumor predisposition disease. Multiple
      neurofibromas are among the characteristic tumors of NF1. The report describes
      the diagnosis and treatment of a large spinal neurofibroma in a NF1 patient. The
      tumor showed a striking pigmentation and was diagnosed as pigmented (melanotic)
      neurofibroma. The distinction between this rare tumor variant and other pigmented
      tumors, especially malignant melanoma, is of primary importance.

PMID- 30112271
TI  - Lung adenocarcinoma presenting with an orbital metastasis.
AB  - Orbital metastasis of lung adenocarcinoma is very rare. The incidence is only
      found to be approximately 7%-12% of lung cancer cases. The lack of knowledge
      about orbital metastasis results in misdiagnosis between malignant or benign
      lesion. This was a case of a 39-year-old woman complaining about a protruding
      left eye and a blind pain in the left eye characterized by hyperemesis eyeball. A
      CT scan of the orbital showed a soft tissue tumor in the fronto-naso-superomedial
      area of the left orbital with suspicion of infiltration of the medial rectus
      muscle, left bulbus oculi, lamina papyracea, and left frontal sinus wall which
      causes proptosis and soft tissue tumor in the left temporal region with suspicion
      of infiltration in the left sphenoid wing with an impression of metastasis. A
      Fine Needle Aspiration Biopsy (FNAB) in the temporal and intra-orbital region
      showed metastatic adenocarcinoma. Moreover, findings of the chest x-ray and chest
      CT scan concluded that there was a tumor in the left lung, and a bronchoscopy
      found adenocarcinoma as the biopsy results.

PMID- 30112272
TI  - A case of pulmonary pleomorphic carcinoma with malignant phenotypes induced by
      ZEB1-associated epithelial-mesenchymal transition.
AB  - A 60-year-old man was admitted to our hospital with non-small cell lung cancer
      (NSCLC). Imaging and pathological studies revealed NSCLC, not otherwise specified
      (NOS), at clinical stage T3N1M0 stage IIIA. We started radiotherapy alone because
      of obstructive pneumonia and end-stage renal disease, but the tumors progressed
      rapidly and resulted in death due to air obstruction by pharyngeal metastasis.
      The cancer was diagnosed as pleomorphic carcinoma in an autopsy. Viable lung
      tumor cells, which were resistant to radiotherapy, and the pharyngeal metastasis
      had mesenchymal phenotypes and expressed ZEB1 but not SNAI1. These observations
      indicated that ZEB1-associated epithelial-mesenchymal transition has malignant
      features including resistance to radiotherapy and aggressive metastatic
      potential. ZEB1-associated EMT may be an important mechanism to understand the
      pathophysiology of pleomorphic carcinoma.

PMID- 30112273
TI  - Detection of KIT mutations in core binding factor acute myeloid leukemia.
AB  - We have investigated the frequency and the effect of KIT mutations on the outcome
      of patients with CBF-AML. 69 patients (34 pediatrics and 35 adults) with CBF-AML
      were enrolled in the study. The frequency of KIT mutations was higher in adults
      compared to pediatrics (22.9% and 14.7%, p = 0.38) respectively. Leukocytosis >=
      20 * 109 /L was significantly associated with pediatrics compared to adults.
      t(8;21)(q22;22) was significantly associated with thrombocytopenia in adults. We
      conclude that no significant difference is found between KIT mutated and
      unmutated CBF-AML in adults and pediatrics. Children with CBF-AML present with
      leukocytosis. t(8;21) is associated with thrombocytopenia.

PMID- 30112274
TI  - The role of FLT3 inhibitors as maintenance therapy following hematopoietic stem
      cell transplant.
AB  - Activating mutations in FLT3 in acute myeloid leukemia (AML) portend a poor
      prognosis, and targeting FLT3 with a tyrosine kinase inhibitor has been an area
      of intense research recently. Most FLT3 mutated AML patients undergo
      hematopoietic stem cell transplantation (HSCT) as standard of care but a
      significant proportion of patients relapse. Although the use of FLT3 inhibitors
      in the pre-HSCT perspective is more clearly defined, its use in the post-HSCT
      scenario, when most relapses occur, remains unclear. In this review, we
      comprehensively present the data on the recent and ongoing studies evaluating the
      role of various FLT3 inhibitors in AML with a particular focus in the post-HSCT
      setting.

PMID- 30112277
TI  - Extra operative intracranial EEG monitoring for epilepsy surgery in elderly
      patients.
AB  - Object: The objective of the study is to investigate and report our experience
      with extra operative intracranial EEG monitoring for evaluation of epilepsy
      surgery among elderly (>= 60 years) patients. Methods: After IRB approval, we
      searched our prospectively maintained epilepsy surgery database to find patients
      who underwent eiEEG at the age of 60 years or older. Electronic medical records
      were reviewed to extract clinical and surgery-related information. Patients who
      underwent resective epilepsy surgery after eiEEG and had at least 1 year of
      clinical follow-up were assessed for seizure outcome. Categorical and continuous
      variables were compared using Pearson chi-square and Student's t-test,
      respectively. Results: A total of 21 patients, with 13 (62%) women, underwent
      eiEEG in our center at the age of 60 years or older. The mean age at time of
      implantation was 63.8 +/- 2.7 years. Sub-dural grids (SDG) were implanted in five
      (24%) patients, whereas sixteen (76%) patients underwent stereo-EEG (SEEG)
      implantation. Median number of contacts in SDG were 106 (56-136) and depth
      electrodes in SEEG were 12 (9-14). There were 2 complications, including one
      mortality due to intracerebral hemorrhage. Sixteen (76%) patients underwent
      respective epilepsy surgery after eiEEG and eleven (69%) achieved Engel class I
      outcome on the last follow-up [mean follow-up duration of 2.7 (+/- 1.8) years].
      Conclusion: We noticed an increased utilization of eiEEG in elderly patients
      after the introduction of SEEG at our center. Overall, we found that eiEEG can
      help achieve good seizure outcomes in the elderly population. However, the one
      eiEEG-related mortality serves a word of caution about the potential risks in
      this population.

PMID- 30112275
TI  - Modulating functional connectivity after stroke with neurofeedback: Effect on
      motor deficits in a controlled cross-over study.
AB  - Synchronization of neural activity as measured with functional connectivity (FC)
      is increasingly used to study the neural basis of brain disease and to develop
      new treatment targets. However, solid evidence for a causal role of FC in disease
      and therapy is lacking. Here, we manipulated FC of the ipsilesional primary motor
      cortex in ten chronic human stroke patients through brain-computer interface
      technology with visual neurofeedback. We conducted a double-blind controlled
      crossover study to test whether manipulation of FC through neurofeedback had a
      behavioral effect on motor performance. Patients succeeded in increasing FC in
      the motor cortex. This led to improvement in motor function that was
      significantly greater than during neurofeedback training of a control brain area
      and proportional to the degree of FC enhancement. This result provides evidence
      that FC has a causal role in neurological function and that it can be effectively
      targeted with therapy.

PMID- 30112276
TI  - Integrated imaging of [11C]-PBR28 PET, MR diffusion and magnetic resonance
      spectroscopy 1H-MRS in amyotrophic lateral sclerosis.
AB  - Objective: To determine the relationship between brain tissue metabolites
      measured by in vivo magnetic resonance spectroscopy (1H-MRS), and glial
      activation assessed with [11C]-PBR28 uptake in people with amyotrophic lateral
      sclerosis (ALS). Methods: Forty ALS participants were evaluated clinically using
      the revised ALS functional rating scale (ALSFRS-R) and upper motor neuron burden
      (UMNB). All participants underwent simultaneous brain [11C]-PBR28 PET and MR
      imaging including diffusion tensor imaging to acquire fractional anisotropy (FA).
      [11C]-PBR28 uptake was measured as standardized uptake values normalized by whole
      brain mean (SUVR). 1H-MRS metabolite ratios (myo-inositol/creatine, mI/Cr; N
      acetylaspartate/creatine, NAA/Cr) were measured within the precentral gyri and
      brain stem (regions known to be involved in ALS pathophysiology), and precuneus
      (which served as a control region). Whole brain voxel-wise correlation analyses
      were employed to identify brain regions exhibiting an association between
      metabolites within the VOIs and [11C]-PBR28 uptake. Results: In the precentral
      gyri, [11C]-PBR28 uptake correlated positively with mI/Cr and negatively with
      NAA/Cr. The same correlations were not statistically significant in the brain
      stem, or in the control precuneus region. Whole brain voxel-wise correlation
      analyses between the estimated brain metabolites within the VOIs and SUVR were
      highly correlated in the precentral gyri. Decreased FA values in the precentral
      gyri were correlated with reduced NAA/Cr and elevated mI/Cr. Higher UMNB was
      correlated with increased [11C]-PBR28 uptake and mI/Cr, and decreased NAA/Cr.
      ALSFRS-R total score correlated positively with NAA/Cr and negatively with mI/Cr.
      Conclusion: Integrated PET-MR and 1H-MRS imaging demonstrates associations
      between markers for neuronal integrity and neuroinflammation and may provide
      valuable insights into disease mechanisms in ALS.

PMID- 30112278
TI  - The application of frequency-domain photoacoustics to temperature-dependent
      measurements of the Gruneisen parameter in lipids.
AB  - The Gruneisen parameter is an essential factor in biomedical photoacoustic (PA)
      diagnostics. In most PA imaging applications, the variation of the Gruneisen
      parameter with tissue type is insignificant. This is not the case for PA imaging
      and characterization of lipids, as they have a very distinct Gruneisen parameter
      compared with other tissue types. One example of PA applications involving lipids
      is the imaging and characterization of atherosclerotic plaques. Intravascular
      photoacoustic (IVPA) imaging is a promising diagnostic tool that can evaluate
      both plaque severity and composition. The literature for IVPA has mainly focused
      on using the difference in absorption coefficients between plaque components and
      healthy arterial tissues. However, the Gruneisen parameters for lipids and their
      behavior with temperature have not been well established in the literature. In
      this study we employ frequency-domain photoacoustic measurements to estimate the
      Gruneisen parameter by virtue of the ability of this modality to independently
      measure both the absorption coefficient and the Gruneisen parameter through the
      use of the phase channel. The values of the Gruneisen parameters of some lipids
      are calculated as functions of temperature in the range 25-45  degrees C.

PMID- 30112279
TI  - All-optical dual photoacoustic and optical coherence tomography intravascular
      probe.
AB  - Intravascular imaging in percutaneous coronary interventions can be an invaluable
      tool in the treatment of coronary artery disease. It is of significant interest
      to provide molecular imaging contrast that is complementary to structural
      contrast provided by optical coherence tomography (OCT) and intravascular
      ultrasound imaging (IVUS). In this study, we developed a dual-modality
      intravascular imaging probe comprising a commercial OCT catheter and a high
      sensitivity fiber optic ultrasound sensor, to provide both photoacoustic (PA) and
      OCT imaging. With PA imaging, the lateral resolution varied from 18 MUm to 40
      MUm; the axial resolution was consistently in the vicinity of 45 MUm. We
      demonstrated the clinical potential of the probe with 2-D circumferential PA and
      OCT imaging, and with multispectral PA imaging.

PMID- 30112281
TI  - Percutaneous transhepatic approach for cryoballoon pulmonary vein isolation in a
      patient with persistent atrial fibrillation and interruption of the inferior vena
      cava.

PMID- 30112280
TI  - Grinding to a halt: Stimulation of the trigeminal cardiac reflex from severe
      bruxism.

PMID- 30112282
TI  - Cryoballoon pulmonary vein isolation after extracardiac Fontan operation.

PMID- 30112283
TI  - Implantation of a cardiac resynchronization therapy device using the anchor
      balloon technique in a patient with a tortuous coronary sinus branch.

PMID- 30112284
TI  - Focal atrial tachycardia and atrial fibrillation from a pulmonary vein aneurysm.

PMID- 30112285
TI  - Epicardial appendage ooze causing pericardial tamponade after left atrial
      appendage device implantation.

PMID- 30112286
TI  - Biatrial flutter circuit involving an anomalous insertion of the Bachmann bundle
      into the superior vena cava.

PMID- 30112287
TI  - Sick sinus syndrome in cardiac noncompaction.

PMID- 30112288
TI  - Psychiatric symptoms and related dysfunction in a general population sample.
AB  - Background: Along with the key clinical features of major psychiatric disorders
      such as psychosis, mania, and depression, these disorders are also associated
      with cognitive, social, and functional deficits. A growing body of evidence
      suggests that these disorders exist at the extreme end of a continuum of symptoms
      rather than as binary entities, so it is plausible that the associated cognitive,
      social, and functional deficits assume a similar pattern. Consistent with this
      approach, we sought to determine whether adults in the general population with
      psychiatric symptoms also demonstrate milder forms of the cognitive, social, and
      functional deficits that are often associated with the psychiatric disorders.
      Methods: Using data from the Study of Resilience and Environmental Adversity in
      Midlife Health (STREAM), which includes survey responses of 811 individuals, we
      compared early academic achievement and self-reported social and functional
      outcomes between respondents who reported psychotic symptoms, manic symptoms,
      depressive symptoms, or no psychiatric symptoms (controls). Results: Adults with
      psychotic symptoms had significantly poorer early academic performance (p = .04)
      and social and functional outcomes (self-reported marital status, p = .021,
      income, p = .001, and health, p < .001) than controls. Adults with depressive
      symptoms had significantly lower early academic performance and income and poorer
      health than controls (p's = 0.033, 0.037, 0.013 respectively), and adults with
      manic symptoms also reported significantly lower rates of marriage than controls
      (p = .006). Conclusions: The results are consistent with the continuum view of
      the etiology of psychiatric disorders in which psychiatric disorders are
      dimensional and experienced in varying degrees of severity across the general and
      clinical population. Importantly, the results highlight the potential impact of
      psychiatric symptomatology on functional outcomes in the population.

PMID- 30112290
TI  - Optimization of instrument conditions for the analysis for mercury, arsenic,
      antimony and selenium by atomic absorption spectroscopy.
AB  - The chemical vapor generation atomic absorption spectrometry technique is
      extremely popular for trace analysis specifically hydride generation continuous
      flow systems for arsenic, antimony, selenium and cold vapor for mercury.
      Optimizing the instrument parameters as well as the hydride generating reactions
      will improve the sensitivity and reliability of the results obtained. The
      advantage of optimizing these conditions increases the production of hydrides or
      vapor species formed thereby improving recoveries. In addition this helps to
      reduce chemical interferences from other species that may compete with the
      analyte of interest for hydride formation. Parameters optimized include: *Reagent
      flow rate*Sample flow rate*Argon flow rate*Acetylene/Air ratio*Concentration of
      reagents*Read delay time For the analytical procedure the flow rate of the
      reagents and sample was affected by the tension on the peristaltic pump and the
      size of the tubing. The optimized flow rate for all reagents was between 0.9-1.0
      mL/min and between 6-7 mL/min for the sample when both conditions were applied.
      The optimized type and concentrations of the reducing agent for Arsenic, Antimony
      and Selenium were NaBH4 (0.6% w/v), NaBH4 (0.7% w/v) and NaBH4 (0.1% w/v) in NaOH
      (0.5% w/v) respectively and SnCl2 (25% w/v) in HCl (20% v/v) for Mercury. The
      concentration and type of acid that produced the optimum signals for Arsenic,
      Antimony and Selenium were 5, 10 and 10 mol/dm-3 respectively. The flow rates for
      the carrier gas (Argon) for Arsenic, Antimony, Selenium and Mercury were
      optimized at 0.2, 0.2, 2.0 and 2.0 mL/min respectively. The optimized flow rate
      for fuel gas (Acetylene) for all the metals except Mercury was 2.5 mL/min. The
      optimized Instrument Read Delay Time for Mercury was 70 s and 20 s for Arsenic,
      Antimony and Selenium.

PMID- 30112291
TI  - Soil heterotrophic respiration assessment using minimally disturbed soil
      microcosm cores.
AB  - Ex-situ measurement of soil respiration is usually done with highly disturbed
      samples that may confound the interpretation and extrapolation of results. We
      have developed a lab respiration assessment method that better simulates field
      conditions and allows efflux estimations based on soil surface area. First,
      intact soil cores are extracted in the field and transferred to the lab. Next,
      soil moisture content and bulk density are assessed in each soil core.
      Immediately following this the soil cores are gently broken, pooled per treatment
      (or plot) and the root systems removed. Subsequently the field moist, non-sieved
      soils are repacked into microcosm cores at their respective bulk densities.
      Moisture content in the microcosms is adjusted to desired levels by adding drops
      of deionized water or by air drying for several hours. After moisture adjustment,
      the cores are pre-incubated at 25  degrees C for two weeks. Afterwards, the
      microcosms are further incubated in the dark at the desired temperatures in
      airtight containers. At incubation times of 0, 48 and 96 h, 20 ml of gas sample
      is collected from each container via the septum, and then injected into pre
      evacuated exetainers for CO2 determination using a gas chromatograph or an
      infrared gas analyzer. Finally, soil efflux is estimated based on the rate of
      linear CO2 increase in the container headspace. One of the advantages of this
      method is that results can be presented per unit of mass (e.g. mg CO2-C g soil-1
      day-1) or area (e.g. g CO2-C m2 day-1). These soil microcosms can also be used to
      simultaneously assess emissions of CH4 and N2O during incubations. This new
      method uses: *Small intact soil cores collected in the field.*Soil
      microcosms.*Efflux calculated per unit of area.

PMID- 30112289
TI  - Validation of an optimised protocol for quantification of microplastics in
      heterogenous samples: A case study using green turtle chyme.
AB  - Quantifying the extent of microplastic (<5 mm) contamination in the marine
      environment is an emerging field of study. Reliable extraction of microplastics
      from the gastro-intestinal content of marine organisms is crucial to evaluate
      microplastic contamination in marine fauna. Extraction protocols and variations
      thereof have been reported, however, these have mostly focussed on relatively
      homogenous samples (i.e. water, sediment, etc.). Here, we present a microplastic
      extraction protocol for examining green turtle (Chelonia mydas) chyme (i.e.
      ingested material and digestive tract fluid), which is a heterogeneous composite
      of various organic dietary items (e.g. seagrass, jellyfish) and incidentally
      ingested inorganic materials (sediment). Established extraction methods were
      modified and combined. This protocol consists of acid digestion of organic
      matter, emulsification of residual fat, density separation from sediment, and
      chemical identification by Fourier transform-infrared spectroscopy. This protocol
      enables the extraction of the most common microplastic contaminants>100 MUm:
      polyethylene, high-density polyethylene, (aminoethyl) polystyrene, polypropylene,
      and polyvinyl chloride, with 100% efficiency. This validated protocol will enable
      researchers worldwide to quantify microplastic contamination in turtles in a
      reliable and comparable way. *Optimization of microplastic extraction from
      multifarious tissues by applying established methods in a sequential
      manner.*Effective for heterogenous samples comprising organic and inorganic
      material.

PMID- 30112293
TI  - What is in the name? Understanding terminologies of patient-centered, person
      centered, and patient-directed care!
AB  - The traditional "medical model" of health care has a paternalistic approach where
      patients are reassured and not decision makers, but some individuals and families
      prefer it. But there are some other confusing terminologies in health-care
      delivery and quality improvement namely patient-centered, person-centered, and
      patient-directed care. By changing the language, it is emphasizing that people
      are more than diseases and their socioeconomic determinants can affect their
      disease trajectories and care choices. Patient-centered denotes more holism and
      empowerment as it promotes and increases the access to personal health
      information through various modes using updated technology such as computers or
      mobile phones and keeping them informed through their active participation.
      Whereas person-centered care would focus on the whole person not just the medical
      conditions. In patient-directed care model, again the approach puts individuals
      in control of decisions about their care. One of the reasons why family medicine
      fraternity sprang up was to provide an antidote for high-tech specialty care that
      did not respect patients' values and concerns which is seen by their emphasis on
      the patient as a whole.

PMID- 30112292
TI  - Disulfiram combats cancer via crippling valosin-containing protein/p97 segregase
      adaptor NPL4.

PMID- 30112294
TI  - Game change in Indian Health Care System through reforms in medical education
      curriculum focusing on primary care- Recommendations of a joint working group.
AB  - Despite the stated aim of Medical Council of India (body regulating medical
      education in India) to produce an Indian Medical Graduate with requisite
      knowledge, skills, attitudes, values and responsiveness, so that he or she may
      function appropriately and effectively as a doctor of first contact of the
      community while being globally relevant, it appears that we failed. The joint
      working group extensively consisting of medical teachers have come up with
      suggestions which may work as the game changer in Indian Health care system. The
      key is to dedicate medical education towards primary care.

PMID- 30112295
TI  - Health at the time of demonetization.
AB  - Health care is one of the key essential services to be traditionally impacted by
      financial turbulences. The Government of India announced the demonetization of
      INR 500 and INR 1000 currency notes in November 2016 to curb corruption and
      introduce economic transparency. The present commentary analyzes the impact of
      this economic reform on the availability/delivery of health-care services and
      also its transient effect on the general population availing such services during
      the first 2 weeks post demonetization. While print and electronic media indicated
      initial setback and displeasure with reference to delivery and access of health
      care services, personal interaction with caregivers or patients suggested that
      there was no lasting adverse effect on health-care delivery. In fact, the
      enthusiasm for a cleaner economy meant for the greater good of the country
      prevailed among the general public and allowed them to bear these hardships. Our
      assessment suggests that demonetization and its consequential transition were
      viewed favorably. Financial and economic reforms initiated in the national
      interest can therefore be managed well with public support.

PMID- 30112297
TI  - A review on interventions to reduce medication discrepancies or errors in primary
      or ambulatory care setting during care transition from hospital to primary care.
AB  - Introduction: Transition of care from hospital to primary care has been
      associated with increased medication errors. This review article aims to examine
      the existing evidence on interventions to reduce medication discrepancies or
      errors in primary or ambulatory care setting during care transition from hospital
      to primary care. Methods: We systematically reviewed the articles in primary or
      ambulatory care setting on patients with care transition that involved medication
      safety, discrepancy, or error as outcome assessment. Primary research articles
      were selected. Interventions in nursing homes or long-term care facilities were
      excluded from the review. Results: We found 6 articles that met the inclusion
      criteria and 4 are prospective cohort study. The key players were pharmacists,
      nurse, and primary care physician. The interventions included care communication,
      medication reconciliation or review, and clarifying medication-related problems.
      Conclusion: There is evidence that interventions in primary care setting reduce
      medication discrepancies on patients with the transition of care from hospital to
      primary care setting. Only one randomized trial involving pharmacist-led
      medication reconciliation was done in an outpatient setting. More good-quality
      randomized controlled trials should be carried out to confirm the evidence.

PMID- 30112296
TI  - Biopsychosocial model of illnesses in primary care: A hermeneutic literature
      review.
AB  - Biopsychosocial model is a useful worldview for primary care or family doctors.
      However, it is often considered as impractical or too complicated. The objective
      of this study is to review the implementation of the biopsychosocial model in
      clinical practice, and its contributions to clinical outcomes. Hermeneutic circle
      literature review was conducted to provide experiential learning in an attempt to
      understand biopscyhosocial model, first developed by George Engel. Literature
      search started with review articles in Medline and Scopus as search engines.
      Citations from previous articles, editorials, and research articles were
      identified and interpreted in the context of the knowledge derived from all
      identified relevant articles. The progress of biopsychosocial model has been
      slow, and primary care doctors do not implement biopsychosocial medicine in their
      practice, while biomedical thinking and approach are still the dominant model.
      Biopsychosocial research addressed chronic illnesses and functional disorders as
      conditions in need for biopsychosocial model implementation. As payment scheme,
      clinical guidelines and clinical performance indicators are biomedically
      oriented, there is no incentive for primary care doctors to adopt biopsychosocial
      model in their practice. Workload and lack of competence in primary care may
      hinder the implementation of biopsychosocial model. Biopsychosocial model helps
      primary care doctors to understand interactions among biological and psychosocial
      components of illnesses to improve the dyadic relationship between clinicians and
      their patients and multidisciplinary approaches in patient care. Biopsychosocial
      model potentially improves clinical outcomes for chronic diseases and functional
      illnesses seen in primary care.

PMID- 30112298
TI  - Jet lag: Heuristics and therapeutics.
AB  - Jet lag is one of those common medical problems, to which most people don't give
      a serious thought. However, it is intricately intertwined with our normal
      circadian rhythm. It is classified as a sleep disorder. There is also a dearth of
      good scientific literature, not to mention clinical trials on the subject. Slowly
      but steadily, the scientific community is realizing the various deleterious
      health effects of jet lag and is devising innovative methods to counter them.
      This narrative review touches upon the etiopathogenesis, clinical manifestations
      and therapeutic strategies effective against the nagging problem of jet lag.

PMID- 30112299
TI  - Ultraviolet radiation and its effects on pregnancy: A review study.
AB  - Seasons and Vitamin D are factors that are directly and indirectly related to
      ultraviolet (UV) radiations and can affect pregnancy. Therefore, the present
      study aims at investigating the effects of being exposed to direct UV radiation
      during pregnancy period and its effects on fetal growth, premature birth, and
      high blood pressure. This study was conducted by searching different websites
      such as Medline, Embase, ProQuest, Global Health, Google Scholar, and Scopus. Of
      the 430 papers found, between 1985 and 2017, seventeen related articles were
      used. The results showed that being exposed to UV radiation during the first 3
      months of pregnancy is associated with improved fetal growth and causes high
      blood pressure during pregnancy. The literature shows that being women exposure
      to UV radiation had beneficial effects on fetal growth and blood pressure during
      pregnancy period. However, since this issue has not been extensively studied in
      the past, the results from previous studies should be generalized with extreme
      care and caution. Therefore, it is suggested that further studies be carried out
      in this area.

PMID- 30112300
TI  - Prevalence and correlates of sexual health disorders among adult men in a rural
      area of North India: An observational study.
AB  - Background and Objectives: Sexual health disorders are an important but less
      researched public health issue in India. We aimed to estimate the prevalence of
      sexual health disorders and their associated factors among adult men in a rural
      community of Haryana, India. Materials and Methods: A community-based cross
      sectional study was conducted among adult men aged 18-60 years using a multistage
      stratified random sampling. Information pertaining to sociodemographic
      characteristics, lifestyle and sexual practices, and self-reported sexual
      problems were collected. Sexual health disorders were defined based on
      International Statistical Classification of Diseases-10 classification of mental
      and behavioral disorders. Step-wise logistic regression was carried out to
      identify factors independently associated with sexual disorders. Results: At
      least one sexual health disorder was reported by 81% of the men. The most
      commonly reported disorder was self-perceived defect in semen (64.4%), followed
      by loss of libido (21%), masturbation guilt (20.8%), erectile dysfunction (5%),
      and premature ejaculation (4.6%). Factors significantly associated with sexual
      health disorders among all men were being never married (odds ratio = 2.04; 95%
      confidence interval: 1.51, 2.77), smoking (1.57; 1.16, 2.14), cannabis use (4.20;
      1.68, 10.48), diabetes (2.40; 1.22, 4.73), and hypertension (3.17; 1.12, 8.92).
      Interpretation and Conclusions: A high burden of sexual health disorders was
      identified among the rural men. Wider recognition of this issue is needed among
      the health-care providers and policymakers.

PMID- 30112302
TI  - Knowledge attitude, and practice regarding dietary salt intake among urban slum
      population of North India.
AB  - Introduction: Hypertension is an important modifiable risk factor for
      cardiovascular disease. High salt intake is an etiological factor for
      hypertension. Any effective salt reduction strategy will be based on people's
      mind-set about salt use. Our objective for this study was to assess the
      knowledge, attitude, and practice for dietary salt intake by urban slum
      populations in Indira Colony, Chandigarh. Methodology: In 2015, we conducted a
      cross-sectional survey among a representative sample of 300 adults aged 18-69
      years using a standardized questionnaire. Variations in the knowledge attitude
      and practice by gender and residence location were compared using the Chi-square
      tests. Results: Most of them (96%) took processed foods and 99% did not bother
      about the salt levels in the food. They also added salt on table. They did not
      buy low-sodium salts. Majority of them (75%) perceived that they are taking right
      amount of salt. They were clueless about the daily recommended allowance. Many
      participants (43%) did not know about the harmful effects of dietary salt. One
      fifth (18%) of them had wrong information about dietary salt. Majority of the
      participants (64%) considered that lowering salt in diet is not important.
      Conclusion: Overall awareness level about optimal salt intake in diet was very
      poor among the slum residents. Recommendation: Development of effective public
      education initiative is the need of the hour for combatting hypertension.

PMID- 30112301
TI  - Monitoring of birth registry coverage and data quality utilizing lot quality
      assurance sampling methodology: A pilot study.
AB  - Background: Effectively monitoring the coverage and quality of data in low
      resource settings is challenging. Lot quality assurance sampling (LQAS) is a
      method to classify coverage as adequate or inadequate. The aim of this pilot
      study is sought to determine the coverage and quality of a birth registry in a
      rural district in Pakistan. Methods: This survey was conducted in 14 clusters of
      Thatta, Pakistan. LQAS methodology was used to monitor the birth registry from
      December 2015 to February 2016. We randomly selected 19 villages from each
      cluster. We used a short questionnaire to review the quality of data collection
      for select variables. Frequency and percentages were reported for categorical
      variables. For data validation, Kappa statistics (kappa) were applied to assess
      the agreement between categorical observations, and the Bland-Altman test was
      used to assess agreement for continuous data. Results: Of the 14 clusters
      sampled, 12 clusters had adequate coverage. Agreement of hemoglobin performance
      between the women's response and information in birth registry data was good
      (kappa = 0.718) (95% confidence interval [CI]: 0.58-0.82); agreement on birth
      outcome recorded by the workers in the registry and as mentioned by women was
      very good (kappa = 1.0); and agreement whether birth weight was assessed within
      48 h of delivery was good (kappa = 0.648) (0.37-0.92). Conclusion: LQAS is a
      powerful tool to monitor coverage and data quality of the birth registry
      maintained by the global network for women's and children's health in Pakistan
      and potentially for data from other surveillance systems.

PMID- 30112303
TI  - Relationship between diet quality and carotid intima-media thickness in people
      with and without carotid atherosclerosis.
AB  - Background: Dietary assessment and management appear to be essential to limit the
      impact of cardiovascular risk. Aim: This study aims to assess the association
      between diet quality as measured by Alternate Healthy Eating Index (AHEI) and
      coronary risk as determined by carotid artery intima-media thickness (CIMT) among
      Saudi adults. Methods: A case-control study was conducted in 210 participants who
      were matched for age and sex and recruited sequentially from King Abdulaziz
      University Hospital, Jeddah, Saudi Arabia. Demographic and anthropometric
      variables were measured in all study participants. Dietary intake was measured by
      food frequency questionnaire. Results: Obesity was highly prevalent among the
      study population. The mean AHEI score for the total sample was found to be 58.3
      +/- 1.67. There were no differences according to the presence and absence of
      atherosclerotic disease; 45% had a poor diet, and 39% had a diet that needs
      improvement. Participants with higher CIMT values tended to be of lower AHEI
      category. Negative correlations were observed between CIMT and AHEI scores and
      components after adjustment for age and energy intake. Conclusions: Adherence to
      a healthier diet, as reflected by a higher AHEI score, is associated with lower
      coronary risk, as estimated by CIMT value, independently from obesity and
      personal behavior factors.

PMID- 30112305
TI  - A cross-sectional study on domestic violence in emergency department of Eastern
      Nepal.
AB  - Introduction: Domestic violence is certainly an important condition, and
      certainly carries significant health consequences. Screening is probably
      acceptable to most patients attending an emergency department. The objective of
      this study is to find out the frequency of domestic violence victims attending
      emergency department, to find out the factors related to domestic violence, type,
      and severity of injury and to identify the impact of domestic violence in the
      victims. Materials and Methods: This was a cross-sectional observational study
      done in the Department of General Practice and Emergency Medicine of BP Koirala
      Institute of Health Sciences from January 2014 to December 2014. Anyone presented
      with a physical injury intentionally caused by a relative, partner, or other
      household member (spouse, partner, sibling, ex-partner, child, and other
      wives/partner of spouse). Results: The total number of patient enrolled in this
      study was 423. Among which 71.9% were female and 28.1% were male. About 27% of
      female and 31.9% of male were in the age group of 20-30 years. Majority (42.4%
      females and 48% males) of the victim's family had agriculture for primary
      occupation. Among the study groups, 40.9% of cases were beaten by direct hit and
      24.3 with weapon, 5% of cases were only reported as rape, and 23.6% as homicidal
      case. Conclusion: Domestic violence is particularly insidious form of gender
      based violence. In the place where they should feel the greatest safety and
      security- the family-women often face terror form of physical, psychological,
      sexual, and economic abuse.

PMID- 30112304
TI  - Musculoskeletal manifestations of tuberculosis: An observational study.
AB  - Background: Data of musculoskeletal manifestations of tuberculosis (TB) are
      limited to case reports, series, or retrospective studies. Therefore, we
      conducted this study to create awareness among doctors about musculoskeletal
      manifestations of TB. Materials and Methods: This was a prospective observational
      study conducted at a referral TB Hospital in North India in September and October
      2016. The aim of our study was to study musculoskeletal manifestations of TB. We
      included patients who had active TB as per the World Health Organization 2010
      criteria. Patients with other chronic illnesses were excluded. A detailed
      history, examination, and appropriate investigations (blood, urine, serological,
      and radiological) of the 100 consecutive patients fulfilling the inclusion
      criteria were recorded. Results: The mean age of patients was 32.16 +/- 12.93
      years. Male-to-female ratio was 43:57. The mean duration of disease was 6.85 +/-
      8.83 months. Of the 100 patients, 60 (60%) had pulmonary TB. The mean duration of
      antitubercular therapy was 1.79 +/- 1.34 months. Fibromyalgia was classified in
      21 (21%) patients, polyarthralgia was seen in 9 (9%), Pott's spine in 7 (7%),
      osteomyelitis in 4 (4%), and scleritis in 2 (2%) patients. Uveitis,
      tenosynovitis, erythema induratum, subcutaneous abscess, and dactylitis were seen
      in 1 (1%) patient each. In 21 patients who had fibromyalgia, 11 developed
      fibromyalgia with the second episode of TB amounting to 60.75% patients.
      Conclusion: This is the first prospective study to look at the musculoskeletal
      manifestations of TB. Patients with active TB were found to have various
      rheumatological manifestations.

PMID- 30112306
TI  - A study of serum Vitamin D level and its association with hypertension.
AB  - Background: Evidence suggests that low levels of Vitamin D may adversely affect
      the cardiovascular (CV) system. Several studies have been done regarding the
      relation and possible causative role of Vitamin D in CV disorders and its well
      known risk factors; however, there are limited studies in this part of the world.
      The aims were as follows: (1) To study the relation between serum Vitamin D level
      between nonhypertensive and hypertensive patients. (2) To study the relation of
      serum Vitamin D levels in patients with isolated systolic hypertension (ISH),
      isolated diastolic hypertension, systolo-diastolic hypertension, and their
      comparison vis-a-vis nonhypertensives. Materials and Methods: A cross-sectional
      study was conducted with 154 patients attending medicine outpatient department of
      a tertiary care hospital of North Bengal from June 2012 to May 2013. The Vitamin
      D was measured by direct ELISA method. Blood pressure (BP) measurements were
      done. Statistical analysis was done by using SPSS 16.0 for Windows. Results: The
      Vitamin D level in the hypertensive group was 22.36 +/- 12.64; ISH Group was
      22.04 +/- 14.26; the isolated diastolic hypertension (IDH) Group was 18.82 +/-
      0.00; and the systolo-diastolic hypertensives (SDH) Group was 22.67 +/- 12.51.
      Then, the mean value of Vitamin D in nonhypertensive Group (27.47 +/- 13.43) was
      significantly (P < 0.05) higher than IDH, SDH, and the hypertensive as a whole
      groups. The relation with ISH Group also reached near significance (P = 0.074).
      There was a negative correlation with BP and serum Vitamin D. This remained
      statistically significant (P = 0.044) for systolic BP (SBP) and near significant
      (P = 0.075) for mean arterial pressure. In population having serum Vitamin D <30
      ng/ml (deficient or insufficient), the negative correlation relationship between
      SBP and serum Vitamin D remains statistically significant (P = 0.010).
      Conclusion: Among the hypertensives, SDH shows significantly lower levels of
      serum Vitamin D. The patients with ISH show a trend, though not statistically
      significant, toward a lower level of Vitamin D compared to the nonhypertensive
      population.

PMID- 30112308
TI  - Factors influencing utilization of reproductive health services among mothers in
      Meghalaya, India.
AB  - Background: Antenatal care (ANC) is one of the basic components where it can
      provide pregnant women with an expansive scope of well-being, health promotion,
      and preventive health services. However, still 830 women die every day from
      preventable pregnancy-related causes, and 99% of these deaths occur in developing
      countries, out of which 20% of these deaths were from India. Objectives: The
      objective of this study is to explore the factors influencing the utilization of
      reproductive health services among mothers and to find the association between
      various factors and utilization of reproductive health services. Methods: A
      community-based cross-sectional study was conducted during January-June 2017
      among 160 mothers who had an infant aged <6 months in Mawkyrwat Block, South West
      Khasi Hills District in Meghalaya. Respondents were selected through simple
      random sampling, and semi-structured questionnaire was used for data collection.
      Data were analyzed using SPSS 16. Results: Mothers attending four or more
      antenatal checkups were 10.6%, where 53.5% of the mothers registered their first
      ANC checkups only by the second trimester and 57.5% preferred home delivery.
      Nearly 52.9% of the mothers were staying more than 5 km away from the health-care
      facilities. The usage of family planning methods was very low, i. e., 96.9% of
      the mothers are not using any of the family planning methods. Conclusion: Study
      finding reveals that the utilization of health-care services was low. Area
      specific approaches such as health camps and mobile clinics might result in
      improved utilization of reproductive health services.

PMID- 30112307
TI  - A randomized, controlled trial comparing the metformin, oral contraceptive pills
      and their combination in patients with polycystic ovarian syndrome.
AB  - Background: Polycystic ovarian syndrome (PCOS) is a condition characterized by
      insulin resistance (IR) and hormonal dysfunction. We conducted a randomized,
      controlled trial comparing the effects of metformin, oral contraceptive pills
      (OCP) and their combination in PCOS. Materials and Methods: We randomized 90
      newly diagnosed PCOS (age 18-40 year, symptom duration >6 months) patients into
      three groups (Group 1-Metformin, Group 2-OCP, and Group 3- Metformin + OCP) in
      this prospective study. We excluded patients with past use of insulin sensitizers
      and hormone therapy. We evaluated for the hyperandrogenism (acne, acanthosis,
      hirsutism, and hormone panel), IR by homeostasis model assessment (HOMA-IR),
      inflammation (high-sensitivity C-reactive protein, fibrinogen, and ferritin), and
      body composition (% fat, android/gynoid ratio) markers at baseline and 6 months
      after therapy. The data were analyzed using appropriate statistical methods and P
      < 0.05 was considered statistically significant. Results: The study population
      had a mean age 23.2 +/- 4.4 years and body mass index of 28.4 +/- 6.1 kg/m2. The
      improvement in the clinical parameters was similar in all the groups. The
      combination therapy showed a better response in reducing inflammatory markers,
      IR, and body composition than either of the groups using a single drug. Metformin
      alone has resulted in a minor reduction of the androgens. None of the patients
      developed significant adverse effect to the given therapy. Conclusion: PCOS is
      managed with either metformin or OCP in many patients. The combination improves
      the hyperandrogenism, body composition, and reduces the inflammatory markers.

PMID- 30112309
TI  - Analysis of tuberculosis case report in Hyderabad district of Telangana state.
AB  - Background: The estimated incidence of TB in India was approximately 28,00,000 as
      per the Global TB report 2017. This accounts for a quarter of the world's TB (Tb)
      cases. National strategic plan, is a programme which aims at the elimination of
      Tb by 2018. The programme is crafted in line with other health sector strategies
      and global efforts, such as the draft National Health Policy 2015, World Health
      Organization's (WHO) End TB Strategy and the Sustainable Development Goals (SDGs)
      of the United Nations (UN). Key strategies under National Strategic plan: Private
      sector engagement, active case finding, drug resistant Tb case management,
      addressing social determinants including nutrition, robust surveillance system,
      community engagement and multisectoral approach. Methods: In March 2018, India Tb
      report was released by RNTCP. An analysis of the report is done in the research
      article, an attempt to take forward end Tb strategy. Result: According to The
      India Tb report, 85% of new TB cases were detected, nationwide, where as 90% of
      new cases were detected in Hyderabad, during the same time period. Tuberculosis
      (Tb) notification rate (per 100 000 population), in India is 138, where as in
      Hyderabad district of Telengana it is 100. Both Public and private sector Tb case
      notification rate, of Hyderabad district was less than that of India (90,10). 6%
      of Tb cases were paediatric cases both Hyderabad and Nationwide. HIV status was
      known in 66% cases, in India and 67% in Hyderabad district of Telengana.

PMID- 30112310
TI  - Health system preparedness in noncommunicable diseases: Findings from two states
      Odisha and Kerala in India.
AB  - Introduction: "Non-communicable diseases (NCDs) are the raging reality of today's
      world and have moved up the priority list of most countries worldwide including
      India. The government of India has launched programs such as National Programme
      for Prevention and Control of Cancer, Diabetes, Cardiovascular disease, and
      Stroke, but little is known about preparedness of health system to address NCDs.
      Methods: A qualitative study was conducted in the states of Odisha and Kerala to
      document the government stakeholder perspectives of health system preparedness
      for NCDs. Results: The study revealed that both the states have a NCD
      preparedness structure but need strengthening at various levels. The present
      human resource is inadequate, over-burdened, and requires specific skills. The
      lack of workforce adversely affects the service delivery mechanism. The study
      highlighted that there is a gap in the timely release of funds and also lack of
      evidence-based application if the information that is made available. Conclusion:
      There is a clear need to fill the gaps and strengthen the identified areas at
      various levels to address the increasing NCD burden. There is also a need to more
      in-depth and large-scale studies on such issues which act as external monitoring
      mechanisms thereby assisting the policy makers and program managers in with
      relevant and scientific evidence to bring reforms in the health system.

PMID- 30112311
TI  - Evaluation of accredited social health activists in Anand District of Gujarat.
AB  - Background: Accredited social health activist (ASHA) has the pivotal role to play
      in the whole design and strategy of national rural health mission (NRHM). The
      performance of ASHA is, therefore, critical for the success of NRHM and hence of
      the health improvement strategy of the government of India. Objectives: (1) To
      evaluate the knowledge and performance of ASHA. (2) To assess the factors
      affecting these two attributes of ASHA. Methods: Ten ASHAs were randomly selected
      from each of the eight administrative blocks of Anand District. Thus, a total of
      80 ASHAs participated in the study. Knowledge of ASHAs was assessed by computing
      knowledge score which included 15 questions, while the performance was assessed
      through performance score which included 17 indicators. Each ASHA was ranked
      "Poor," "Average," and "Good" based on the performance score. Results: Out of 80
      ASHAs, 49 (61%) were in the age group of 30-40 years. Majority of ASHAs(68%)
      belonged to other backward class (OBC). 73 (91%) ASHAs had education up to at
      least secondary level. 65 (81%) ASHAs were working for more than 4 years. About
      84% of ASHAs had knowledge score between 12 and 15. Nearly 51% of ASHAs ranked
      average in performance, while 49% ranked poor. None of the ASHAs ranked good.
      Knowledge score and performance ranks were not associated with age, caste,
      education, and duration of service of ASHAs. Performance ranks were found to be
      significantly associated only with time lapse since the last training received.
      Conclusion: To strengthen the grass root cader of ASHAs, their evaluation should
      be conducted regularly. Additional refresher training should be provided to ASHAs
      with low knowledge and performance scores so that the engagement of rural
      community with the health system can be improved.

PMID- 30112312
TI  - Prevalence of Helicobacter pylori infection in upper gastrointestinal tract
      disorders (dyspepsia) patients visiting outpatient department of a hospital of
      North India.
AB  - Background: Helicobacter pylori infection is a major health ailment in developing
      countries. The infection is related with high morbidity and mortality ranging
      from chronic gastritis to gastric malignancies. The prevalence of H. pylori
      infection greatly varies from country to country and region to region. The aim is
      to study the prevalence of H. pylori infection in upper gastrointestinal (GI)
      tract disorders (dyspepsia) patients. Methods: The study was carried out in an
      outpatient department, India. Patients presenting with dyspeptic symptoms were
      subjected to serological investigation and upper GI endoscopy, histopathological
      examination, and rapid urease test of specimen. Diagnosis of H. pylori infection
      was made if one or both diagnostic test results were positive. Results: H. pylori
      infection was diagnosed in 85% of patients. There was no significant difference
      in sex- and age-related distribution (<50 years' age group and >50 years' age
      group) of H. pylori infection. However, association of H. pylori infection was
      positive in 83.3% (45) of patients with endoscopic abnormalities (54).
      Conclusion: The prevalence of H. pylori infection is high in the study
      population. Early detection and prompt treatment are essential for prevention of
      serious complications.

PMID- 30112313
TI  - Profile of aluminum phosphide poisoning in a tertiary care institute in the sub
      Himalayan region.
AB  - Context: Aluminum phosphide (ALP) is a highly toxic agricultural fumigant
      pesticide commonly implicated in poisoning. Aim: The aim of the study was to
      study the profile of patients presenting with ALP poisoning in Dr. RPGMC Kangra,
      Tanda, Himachal Pradesh. Settings and Design: This was a retrospective study
      conducted in the Department of Medicine at Dr. RPGMC Kangra, Tanda, Himachal
      Pradesh, from August 2011 to January 2014. Material and Methods: Case record
      forms of 117 patients were reviewed and analyzed. Data were collected for
      sociodemographic and clinical parameters. Outcome of patients was recorded as
      expired and improved. All the patients were managed symptomatically. Statistical
      Analysis: Statistical analysis was performed using SPSS version 15. P < 0.05 was
      considered statistically significant. Results: Out of the total 117 patients
      included in the study, 61 (52.1%) were males and 56 (47.1%) were females. Mean
      age +/- standard deviation of presentation was 30.9 +/- 12.2 years. About 70% of
      the patients were from rural background. Out of the total 117 patients, 68
      (58.1%) patients had expired and 49 (41.9%) had improved. Most of the patients in
      the expired group consumed ALP in tablet form (54.7% of the total). Nearly 57% of
      the patients had leukocytosis at presentation and <5% had leukopenia. The mean
      pulse rate and mean systolic blood pressure in the expired group were 116.24 +/-
      14.3 per minute and 89.9 +/- 16.83 mmHg which was statistically significant. The
      mean change in creatinine value (DeltaCr) in the expired group was 1.03 +/- 0.36
      which was statistically significant. Conclusions: The prognosis of the patients
      can be anticipated on assessing the cardiac status and mean change in creatinine
      value (DeltaCr) at the time of admission.

PMID- 30112314
TI  - Prevalence of thyroid dysfunction in chronic obstructive pulmonary disease
      patients in a tertiary care center in North India.
AB  - Introduction: Thyroid dysfunction can cause inspiratory and expiratory muscle
      weakness in patients with or without chronic obstructive pulmonary disease (COPD)
      Thyroid dysfunction in COPD results in increased frequency of exacerbation thus
      lead to poor quality of life. It may further increase cardiovascular disease risk
      thereby increasing mortality. Aims and Objectives: This study was conducted to
      evaluate the prevalence of thyroid dysfunction and hence that the quality of life
      of COPD can be improved. Materials and Methods: This is a cross-sectional -
      prevalence study. The study was conducted over a period of 1 year from August
      2015 to July 2016. The study group was consists of male and female COPD patients
      diagnosed with spirometry and severity was determined according to the global
      initiative for chronic obstructive lung disease classification criteria. The
      patients were enrolled in this study from medicine outpatient department (OPD),
      respiratory OPD and those admitted to indoor wards of Medicine Department.
      Patients were screened for thyroid dysfunction. Results: Out of 171 patients,
      thyroid dysfunction was present in 43 patients. All of them were hypothyroid. The
      prevalence of thyroid dysfunction was 25%. In Stage A it was 20.5%, Stage B
      25.7%, Stage C 23.4%, and in Stage D 30.4%. Thyroid dysfunction was associated
      with more frequent exacerbation. Conclusion: Thyroid dysfunction is a common
      extrapulmonary manifestation in COPD patients. It is associated with frequent
      exacerbations which affect the quality of life in these patients. Early detection
      and proper management can improve the quality of life in these patients.

PMID- 30112315
TI  - Epidemiological profile of multidrug-resistant tuberculosis patients in Gorakhpur
      Division, Uttar Pradesh, India.
AB  - Introduction: Multidrug-resistant tuberculosis (MDR-TB) poses a major threat to
      control of TB worldwide. Adequate information on socioepidemiological factors and
      their interaction is required for its control. The aim was to study the social
      and epidemiological profile of MDR-TB patient in Gorakhpur division. Methodology:
      A cross-sectional study of 157 MDR-TB patients from Gorakhpur division admitted
      at DR-TB Center of a tertiary care center were interviewed during initiation of
      MDR-TB treatment using structured questionnaire and collected data were described
      using descriptive statistics. Results: More than 2/3rd of patients were male and
      the mean age was 32.15 +/- 13.19 years. Overcrowding was present in 82.8% of
      households and ventilation of living room was inadequate in 72.7% of households.
      About 21.7% had history of contact with TB cases. Two-third of the patients
      practice unhygienic sputum disposal practices at home and at public places it was
      more than 90%. More than 60% of patients have the history of irregular treatment
      in intensive phase and 80% in continuation phase. Nearly 68.8% of patients were
      resistance to isoniazid (H) and rifampicin (R) and 18.5% were resistance to H, R,
      and S (streptomycin) followed by H, R and E (Ethambutol). Nearly 3.8% of patients
      were HIV positive and 7% had history of diabetes. 64.3% were under severe
      thinness category according to the WHO classification. Conclusion: Study point
      out need of nutritional counseling and support throughout the treatment. Use of
      incentives, enhancing contact tracing and increasing awareness regarding sputum
      disposal practices are recommended for effective control.

PMID- 30112316
TI  - Mothers' preferences toward breaking bad news about their children cancer.
AB  - Background: The responsibility of breaking bad news (BBN) to patients is one of
      the most difficult tasks of a medical profession. Aim: The current study aimed to
      investigate the preferences of mothers of children with cancer about BBN.
      Materials and Methods: In this cross-sectional study was conducted in Mashhad
      during years of 2016, 62 mothers of children with cancer at Dr-Sheikh hospital
      were recruited by convenience sampling and completed a questionnaire including
      demographic data and 20 questions about the mothers' preferences to BBN. Data
      displayed as percent by SPSS V20 software. Results: Mothers preferred that BBN
      conducted by their child's doctor (93.5%), with an emotional and compassionate
      way (83.9%), and in a private setting (90.3%). Be told completely about the
      process of diagnosis (98.4%), meet people with similar conditions (83.9%),
      receive psychological (85.5%), and religious (79%) support after getting bad
      news, being in touch with a close relative (82.3%) and applying another term-like
      malignancy instead of cancer (95.5%). Conclusion: We tried providing helpful
      information for developing national guidelines about how to breaking news in
      Iran, by doing this study.

PMID- 30112318
TI  - Determining the effect of implementing an educational package on quality of life
      among patients with chronic obstructive pulmonary disease referring to teaching
      hospitals affiliated with Ilam University of Medical Sciences in 2016.
AB  - Introduction: Nowadays, pulmonary diseases have become one of the most important
      causes of mortality in the world. In this regard, the present study was aimed at
      examining the effect of implementing an educational package on quality of life
      (QoL) among patients with chronic obstructive pulmonary disease (COPD) referring
      to teaching hospitals affiliated with Ilam University of Medical Sciences.
      Materials and Methods: The present study was an interventional clinical trial in
      which the participants were randomly assigned into an intervention group and a
      control group. The statistical population included all COPD patients who had
      referred to the teaching hospitals affiliated with Ilam University of Medical
      Sciences. Sixty patients were selected by a convenience sampling method out of
      the whole patients who had referred to Shahid Mostafa Khomeini Hospital in Ilam.
      Afterward, they were randomly assigned into an intervention group and a control
      group (each including 30 patients). The collected data were analyzed using
      descriptive statistics; Chi-square test, independent and paired samples t-test,
      and correlational tests at a significance level of 0.05. Results: The results of
      the present study showed that as a result of the educational package, the
      intervention patients had a significantly higher QoL than the control patients (P
      = 0.001). The results also showed that implementing the educational package had a
      significant effect on QoL among the intervention patients in dimensions of
      physical function, mental health, social status, playing physical role, playing
      emotional role, physical pains, general health, and energy and vitality (P =
      0.001). Conclusion: Based on the results of the present study, it can be
      concluded that collaborative education is a significant issue in health and
      treatment, and different dimensions of QoL can be enhanced by an appropriate
      educational program.

PMID- 30112317
TI  - Evaluation of physicians' skills in breaking bad news to cancer patients.
AB  - Background: Delivering bad news to patients is one of the most difficult tasks of
      physicians that play a big role in the process of treatment and cooperation of
      patients. The objective of this study is to evaluate the ability and skills of
      physicians in delivery bad news to cancer patients. Methods: This study is a
      cross-sectional study performed on 70 specialist physicians in two hospitals of
      Mashhad in 2016. Data were collected by Persian questionnaire of SPIKES included
      16 questions and were analyzed by SPSS software. Results: In this study, among
      the questionnaire items, the most prevalent item was not giving the bad news by
      phone (100%) and the least prevalent item was putting the hand on the shoulder
      (24.3%). This study showed that 81.4% of doctors agreed on giving the bad news in
      private, 72.9% agreed on giving relative hope to patients and 67.1% agreed on
      evaluating patients knowledge of his/her disease when giving bad news.
      Conclusion: The results of this study show that the ability of physicians in
      giving bad news is not enough in some aspects. Therefore, holding educational
      courses during physicians' education and after graduation are recommended to
      increase patients' trust and decreasing worries and inconvenience of physicians
      in difficult situations of delivering bad news.

PMID- 30112319
TI  - Investigating the effect of education on health-promoting lifestyle among the
      elderly of Ramsar in 2017.
AB  - Introduction and Objective: Providing and enhancing the level of health are one
      of the essential needs of all people, and implementation of health promotion
      lifestyle is the most important and effective factor in maintaining and improving
      the health of the elderly. The present study aimed at defining the effect of
      aging on health-promoting lifestyle. Methodology: This randomized clinical trial
      was conducted on 72 individuals from the retirees clubs of Education department,
      Social Security, and Health centers in Ramsar, in 2017. Sampling was done
      randomly with blocking and random allocation in two groups: Experimental and
      control. Data were collected in two steps by Demographic profile questionnaire,
      AMT, ADL, OHI and HPlP II which validity and reliability of them were confirmed.
      Participants attended eight training sessions (twice each week). Data analysis
      was performed with the use of SPSS 18 and descriptive (Frequency) and analytic
      tests (Chi-square, Fisher's exact test, Independent Sample t test and Paired
      Sample t test) with a significance level of 0.05. Results: The results showed
      that the mean age of the elderly was 64.4 +/- 4.1 years. The mean score of
      lifestyle enhancement was 148.59 and 173.25 before and after training in the
      experimental group, respectively. Based on the results of paired t-test (P < 0.
      323), there was no significant difference between the mean life expectancy of
      elderly health promotion in control group before and after educational
      intervention; however, there was a significant difference between the two groups
      before and after training (P = 0.001). Conclusion: Educational programs play an
      important role in integrating health-promoting lifestyle to encourage the elderly
      to accept more accountability regarding health, sustained physical fitness,
      proper nutrition, healthy interpersonal relationships, expected spiritual growth,
      and the proper management of stress and anxiety in life.

PMID- 30112320
TI  - Spontaneous intracranial hemorrhage associated with dengue fever: An emerging
      concern for general physicians.
AB  - Dengue fever (DF) is an arboviral disease caused by a positive-sense RNA virus of
      the genus Flavivirus. The overall incidence of DF has increased exponentially
      worldwide over the last three decades. The atypical clinical manifestations of DF
      grouped under expanded dengue syndrome (EDS), have also been reported more
      frequently for the last decade. These unusual manifestations are usually
      associated with coinfections, comorbidities, or complications of prolonged shock.
      Intracranial hemorrhage (ICH) is one of the rare manifestations of the central
      nervous system involvement by dengue as a part of EDS. The pathogenesis and
      treatment of this manifestation also remain controversial. Therefore, we report a
      case of a previously healthy 65-year-old female who developed ICH as a part of
      EDS along with a brief review of literature.

PMID- 30112321
TI  - Long-term relief from tension-type headache and major depression following
      chiropractic treatment.
AB  - We report the case of a 44-year-old school teacher who experienced long-term
      relief from tension-type headache (TTH) and major depression following
      chiropractic treatment. It is well recognized that psychiatric comorbidity and
      suicide risk are commonly found in patients with painful physical symptoms such
      as chronic headache, backache, or joint pain. Recent studies indicated that
      autonomic dysfunction plays a role in the pathogenesis of TTHs and depressive
      disorders. The autonomic nervous system is mainly controlled by reflex centers
      located in the spinal cord, brain stem, and hypothalamus. This report highlights
      the rewarding outcomes from spinal adjustment in certain neuropsychiatric
      disorders. Long-term results of chiropractic adjustment in this particular case
      were very favorable. Further studies with larger groups are warranted to better
      clarify the role of chiropractic.

PMID- 30112322
TI  - First reported case of naturally acquired fatal anthrax from Northeast India.
AB  - Anthrax is a zoonotic disease and is caused by Bacillus anthracis which is a Gram
      positive, nonmotile, spore-forming rod, found in soil. The spores can remain
      viable for decades. Transmission occurs naturally in humans by direct contact
      with infected animals or the contaminated animal products. Anthrax is a major
      health problem in eastern and southern India, with a significant human incidence
      because the disease is poorly controlled. Here, we discuss such a case of
      naturally occurring fatal anthrax in North-East India. A 48-year-old man from
      Assam presented with seizures, hematemesis, and fever. Apart from altered mental
      status and nonreactive pupils, his cutaneous and systemic examination was
      unremarkable. Noncontrast computed tomography head showed multiple hemorrhages.
      Blood and cerebrospinal fluid showed heavy growth of anthrax Bacilli. He was
      started on specific antibiotics after the reports, but unfortunately, the patient
      succumbed to infection. Due to high prevalence of anthrax in the endemic regions,
      a high degree of suspicion is required to clinch the diagnosis. Early initiation
      of therapy before developing the intracranial hemorrhagic complications might
      result in a better outcome. Careful history for a possible exposure to animal
      carcass or a suspected animal death due to anthrax will also help in early
      diagnosis of the disease and effective therapy.

PMID- 30112323
TI  - Hyperechoic amniotic fluid in a term pregnancy.
AB  - The presence of highly echogenic amniotic fluid (AF) is uncommon, and presence
      creates a dilemma in the mind of the clinician. Echogenic AF has been attributed
      to meconium, blood, and vernix caseosa. Many studies have shown that the presence
      of meconium is unlikely in most cases. We report a case of highly echogenic AF
      detected at 37 weeks which was managed conservatively with careful fetal
      monitoring for further 2 weeks expecting spontaneous onset of labor. Labor was
      induced due to reduced fetal movements at 39 weeks. Healthy baby weighing 3130 g
      was delivered by cesarean section after a failed induction with prostaglandin.

PMID- 30112324
TI  - Management of foreign body ingestion in children with cerebral palsy: Need for
      proper trauma management protocol.
AB  - Cerebral palsy (CP) is described as a group of permanent, nonprogressive movement
      disorders that cause physical disability in development and further affecting
      body movement and muscle coordination. The condition develops when certain
      abnormalities persist inside the developing brain that ultimately disrupts the
      brain's ability to control movement and maintain posture and balance. Patients
      with CP are more susceptible to dental trauma due to the lack of muscle
      coordination and unexpected involuntary movements. The present case series
      highlights the need for emergency protocol management when these patients report
      with dental trauma and complications which can happen in dental office. The first
      case report is about ingestion of permanent incisor following trauma which was
      diagnosed incidentally in the abdominal radiograph, and the second case is
      reported to be accidental ingestion of head of dental mouth mirror during the
      routine oral examination. These two case reports emphasize the need for more
      comprehensive trauma management protocol in these children.

PMID- 30112325
TI  - Vitamin B12 deficiency presenting with hyperpigmentation and pancytopenia.
AB  - Hyperpigmentation with generalized weakness may be the initial presentation of
      several systemic conditions. Vitamin B12 deficiency can present very rarely as
      hyperpigmentation. Association of pancytopenia at this stage is even rare. Early
      identification and management can prevent various neurological complications.
      Here, we report a rare case of Vitamin B12 deficiency presenting as
      hyperpigmentation and pancytopenia.

PMID- 30112326
TI  - Appropriately reporting results using the medication subscale of the summary of
      diabetes self-care activities measure: A comment on Dasappa et al. (2017).

PMID- 30112327
TI  - Cautious use of absolute and relative precision while calculating sample size.

PMID- 30112328
TI  - Effect of valproic acid on survival in glioblastoma: A prospective single-arm
      study.
AB  - Background: Retrospective evidence suggests that valproic acid (VPA), an
      antiepileptic drug, is associated with improved outcomes in glioblastoma. The
      exact mechanism of interaction of VPA with radiation and temozolomide (TMZ) is
      still unclear. Laboratory studies show that VPA can enhance tumor cell kill while
      at the same time protect the normal neural tissue. The aim of this study was to
      prospectively evaluate the benefit of VPA on outcomes in glioblastoma. Materials
      and Methods: In this single-arm prospective study, patients of glioblastoma were
      started on seizure prophylaxis with VPA (15-20 mg/kg/day) following maximal safe
      resection. All patients were treated with chemoradiation to a dose of 60 Gy in 30
      fractions with concurrent TMZ followed by adjuvant TMZ for 6 cycles. VPA was
      continued during adjuvant treatment and follow-up. Survival analysis was done
      using Kaplan-Meier analysis. Results: Twenty patients were enrolled in the study.
      Median age was 47 years. M:F ratio was 3:1. Treatment was well tolerated with no
      grade 3/4 adverse events. 8/20 patients experience seizure episodes during
      treatment and/or follow-up which needed additional antiepileptic drugs for
      control. Median progression-free survival (PFS) and overall survival (OS) were 10
      months and 16 months, respectively. Younger patients (age <=45 years) showed a
      significantly better OS (25 months) versus older patients (8 months) (P = 0.002).
      Conclusions: Incidence of seizures on VPA prophylaxis was 40%. Median PFS and OS
      were comparable to historical controls. There was no significant treatment
      related toxicity. The results need validation in larger prospective randomized
      studies.

PMID- 30112329
TI  - Profile of non-Hodgkin lymphoma: An Indian perspective.

PMID- 30112330
TI  - Breast-conserving radiotherapy with simultaneous integrated boost; field-in-field
      three-dimensional conformal radiotherapy versus inverse intensity-modulated
      radiotherapy - A dosimetric comparison: Do we need intensity-modulated
      radiotherapy?
AB  - Background and Purpose: To examine the feasibility of improving breast-conserving
      radiotherapy with simultaneous integrated boost (SIB) and analyzing the
      efficiency of forward versus inverse intensity-modulated radiotherapy (IMRT)
      techniques in providing the same. Materials and Methods: Three-dimensional
      conformal radiotherapy (3DCRT) field-in-field (FIF) plans with simultaneous and
      sequential boost and IMRT SIB plans were generated for the datasets of 20
      patients who had undergone breast-conserving surgery. The 3 plans were compared
      dosimetrically for efficiency in terms of planning target volume (PTV) coverage
      (PTV 95%), homogeneity and conformity, dose delivered to
      ipsilateral/contralateral lungs (I/L: V10, V20, C/L: Vmean, V5), heart and
      contralateral breast (Vmean, V30 for heart and Vmean, V1, V5 for C/L breast).
      Results: The FIF 3DCRT plan with SIB (PLAN B) was more homogeneous than the
      classical technique with sequential boost (PLAN A). There were less hot spots in
      terms of Dmax (63.7 +/- 1.3) versus Dmax (68.9 +/- 1), P < 0.001 and boost V107%,
      B (0.3 +/- 0.7) versus A (3.5 +/- 5.99), P = 0.001. The IMRT SIB (PLAN C) did not
      provide any significant dosimetric advantage over the 3DCRT SIB technique. IMRT
      SIB plan C was associated with increased dose to contralateral lung in-terms of
      V5 (10.35 +/- 18.23) vs. (1.13 +/- 4.24), P = 0.04 and Vmean (2.12 +/- 2.18)
      versus Vmean (0.595 +/- 0.89), P = 0.008. There was 3-fold greater exposure in
      terms of Monitor Unit (MU) (1024.9 +/- 298.32 versus 281.05 +/- 20.23, P < 0.001)
      and treatment delivery time. Conclusions: FIF 3DCRT SIB provides a dosimetrically
      acceptable and technically feasible alternative to the classical 3DCRT plan with
      sequential boost for breast-conserving radiotherapy. It reduces treatment time by
      2 weeks. IMRT SIB does not appear to have any dosimetric advantage; it is
      associated with significantly higher doses to contralateral lung and heart and
      radiation exposure in terms of MU.

PMID- 30112331
TI  - Geographical pattern of carcinoma gallbladder in Bihar and its association with
      river Ganges and arsenic levels: Retrospective individual consecutive patient
      data from Regional Cancer Centre.
AB  - Background: Indo-Gangetic basin is known to have higher incidence of gallbladder
      cancer. Proximity to River Ganga and high heavy metal in soil exposure have been
      postulated as risk factors. Aim: This study aims to evaluate the geographical
      pattern of gallbladder cancer from consecutive patient database enrolled in
      hospital-based cancer registry (HBCR). Objectives: To evaluate demographic
      profile and districtwise/zonewise dispersion of gallbladder cancer cases
      registered in HBCR from year 2014 to 2016. To evaluate association of carcinoma
      gallbladder (CaGB) due to proximity of Ganges, districts of high soil arsenic
      levels and referral bias. Materials and Methods: Demographic profile and district
      based location of individual consecutive gallbladder cancer patient registered in
      Regional Cancer Centre from the year 2014 till 2016 were analyzed. Population
      data from 2011 census and arsenic soil content data from central groundwater body
      were obtained. Frequency distribution, cross tabulation, and odds ratio were used
      to analyze risk of CaGB across population subsets in Bihar. Results: A total of
      1291 consecutive patients of CaGB were registered from 2014 to 2016. Median age
      at diagnosis was 55 years (range 18-95 years). Male to female ratio was 0.6.
      Patna (16%) followed by Vaishali (5.8%), Sitamarhi (5%), Madhubani (4.7%), Gaya
      (4%), and Samastipur (4%) had highest cases. Districts along main central River
      Ganga (n = 12) and those exposed to high arsenic soil content (n = 15) had higher
      odds ratio for CaGB, 1.72 (95% confidence interval [CI]: 1.54-1.91, P = 0.001),
      and 1.45 (95% CI: 1.30-1.62, P = 0.001), respectively. Districts within 100 km
      radius of our institute had higher gallbladder cancer cases, odds ratio 1.81 (95%
      CI: 1.62-2.03, P = 0.001), suggesting significant referral bias predominantly
      contributed by cases registered under Patna and Vaishali districts. Conclusion:
      CaGB is major public health problem in Bihar. Exposure to high soil arsenic
      levels and proximity to River Ganga are strongly associated with gallbladder
      cancer. Systematic population-based longitudinal studies are needed to explore
      above hypothesis.

PMID- 30112332
TI  - Isolated central nervous system blast crisis in a case of chronic myeloid
      leukemia on dasatinib.

PMID- 30112333
TI  - Metastatic Gastric cancer: Real world scenario from a developing country.
AB  - Aim: Data on epidemiology and outcome in metastatic stomach carcinoma patients
      from India are scarce. We aimed to evaluate clinical features and treatment
      outcome in patients treated at our center. Materials and Methods: This is a
      single institutional review of metastatic gastric carcinoma patients treated
      between May 2011 and October 2016. Patients who received at least one cycle of
      chemotherapy were included for modified intent-to-treat survival analysis.
      Results: total of 143 patients were diagnosed with metastatic stomach carcinoma
      with a median age of 56 years (range: 29-86). The most common symptoms were
      abdominal pain in 112 (78%) patients. The most common site was body in 81 (57%)
      patients. Common site of metastasis was peritoneum in 86 (60%) and liver in
      (62%). Seventy-one (50%) patients were eligible for survival analysis. Common
      chemotherapy regimens were capecitabine-cisplatin in 27 (38%) and EOX in 22 (31%)
      patients. Survival status could not be assessed in 29 (41%) patients who lost to
      follow-up. After a median follow-up 9.7 months (range: 0.5-37.7), median
      progression-free survival (PFS) was 7.9 months (range: 0.5-23.9) and median
      overall survival (OS) was 12.2 months (range: 0.5-37.7). The Eastern Cooperative
      Oncology Group (ECOG) performance status (PS) >=2 and the presence of linitis
      plastica showed a trend toward inferior PFS (P = 0.052 and 0.053, respectively)
      only in univariate analysis. Female sex and ECOG PS >=2 predicted inferior OS in
      both univariate and multivariate analysis (P = 0.012, 0.02 and 0.03 and 0.05,
      respectively). Conclusions: Platinum-based doublet chemotherapy was used in the
      majority of patients. The overall outcome was comparable to that of the available
      literature. Female sex and ECOG PS >=2 predicted the inferior outcome.

PMID- 30112335
TI  - The epidemiology, treatment, and determinants of outcome of primary head and neck
      cancers at the Jos University Teaching Hospital.
AB  - Introduction: This study aims to evaluate the epidemiology, treatment, and
      factors that determine the outcomes of head and neck cancers (HNC). Patients and
      Methods: Retrospective analytical review of HNC managed at the Jos University
      Teaching Hospital between May 2007 and April 2017 using the International
      Classification of Diseases version 10. Results: Of 487 head and neck neoplasms,
      129 (26.5%) were malignant and 122 health records met the criteria for analysis
      consisting of 83 (68.0%) males and 39 (32.0%) females aged 13 years to 85 years
      (mean = 51 years; standard deviation = +/-16.0 years). The most common presenting
      feature was nasal obstruction (n = 47; 38.5%). The most common tumor site was the
      nasopharynx (n = 34; 27.9%). Mean duration of symptoms was 13.3 months. Alcohol
      (P = 0.02), cigarette smoking (P = 0.01), and cooking wood smoke (P = 0.01) were
      associated with advanced tumor stage. Squamous cell carcinoma was the most common
      histological type. Posttreatment complication rate was 47.5%. Lost to follow-up
      rate was 55.7%. The lungs were the most common distant metastatic site. The case
      fatality rate was 18.0%. Conclusion: HNC constitutes almost a quarter of head and
      neck tumors affecting twice the number of males in their sixth decade with
      nasopharyngeal cancers being the most common in both genders. Several modifiable
      variables are noted to target appropriate future cancer education for lifestyle
      modification, screening for early detection and treatment.

PMID- 30112334
TI  - Robotic radiosurgery treatment in liver tumors: Early experience from an Indian
      center.
AB  - Purpose: The purpose of this study is to report CyberKnife experience in
      hepatocellular carcinoma (HCC) and liver metastasis (LM). Materials and Methods:
      Fifty liver lesions in 31 consecutive patients with liver lesion [mean age 54.5
      years (range 32-81 years), 77% were male patient, GTV <10cc in 5 patients, 11
      90cc in 18 & >90cc in 8 patients respectively. Eighty percentage (25/31) had
      prior treatment (chemotherapy 18 patient & TACE in 7 patients). Dosage schedule
      was 21-45Gy/3# (mean PTV dose 33Gy, Prescription isodose 84%, target coverage
      94%). Mean CI, nCI & HI were 1.19, 1.31 & 1.18 respectively. Mean liver dose was
      5.4 Gy, 800 cc liver dose 11.1 Gy. Results: At mean follow-up of 12.5 months
      (range 1.9-44.6 months), 19 patients were expired and 12 were alive (nine patient
      with stable disease, two local progression, and one with metastasis). Median
      overall survival (OS) of all patients are 9 months (1.9-44.6 months), in HCC
      patients 10.5 months (2.1-44.6 months) and MT 6.5 months (1.9-24.6 months)
      respectively. Gr-I-II GI toxicities were in 11/50 (22%) patients. OS was
      influenced by PS (Karnofsky Performance Status 70-80 vs. 90-100: 9.9 vs. 16.4; P
      = 0.024), Child-Pugh (CP A/B vs. C: 23.6 vs. 6.5; P = 0.069), cirrhosis (only
      fatty liver vs. diffuse cirrhosis: 17.8 vs. 10.6; P = 0.003), prior treatment (no
      Rx vs. prior Rx: 30.1 vs. 8.2; P = 0.08), number of lesions (single vs. multiple:
      16.4 vs. 6.9; P = 0.001), and target volume (<10 cc vs. >90 cc: 24.6 vs. 11.2; P
      = 0.03). Conclusion: Stereotactic body radiation therapy is a safe and effective
      treatment. Patient related factors such as performance status, Child-Pugh
      classification, cirrhosis status, prior treatment, number of liver lesion &
      target volume (GTV) influence the survival functions.

PMID- 30112336
TI  - Efficacy and safety of nimotuzumab in unresectable, recurrent, and/or metastatic
      squamous cell carcinoma of the head and neck: A hospital-based retrospective
      evidence.
AB  - Context: Role of nimotuzumab in locally advanced head and neck cancer (HNC) is
      well established in India; however, no clinical evidence is available for its
      role in recurrent and/or metastatic HNC. Aims: The aim of this study is to
      evaluate the efficacy and safety of nimotuzumab when added to standard treatment
      in unresectable, recurrent, and metastatic squamous cell carcinoma of the head
      and neck (SCCHN). Settings and Design: Hospital records of 14 patients diagnosed
      with recurrent and/or metastatic HNC with histologically confirmed squamous cell
      carcinoma and being treated with nimotuzumab along with standard treatments from
      December 2010 to December 2016 were retrospectively evaluated. Subjects and
      Methods: The tumor response rate and overall survival (OS) were analyzed.
      Toxicity and adverse events (AEs) were assessed as per common terminology
      criteria for adverse events (CTCAE) v 4. Results: Oral cavity was most commonly
      involved region followed by hypopharynx and oropharynx. At 24 weeks after
      completion of treatment, overall response rate (complete response (CR) + partial
      response (PR)) was 75%. Survival rate at 1, 2, and 3 years was 77.80%, 64.81%,
      and 64.81%, respectively. At a median follow-up of 15.17 months, median OS was
      not reached. All AEs were either Grade I (66.7%) or Grade II (33.3%). No Grade
      III or Grade IV AEs were observed. No added toxicity was observed due to
      nimotuzumab. Conclusions: In the first of its kind study, the addition of
      nimotuzumab to standard treatment showed promising response rate as well as
      survival outcomes in recurrent and/or metastatic SCCHN patients without producing
      additional toxicity.

PMID- 30112338
TI  - Ipilimumab: A tale of twists and turns.

PMID- 30112337
TI  - Bone marrow limited diffuse large B-cell lymphoma following prolonged
      immunosuppressive therapy with methotrexate and corticosteroids.

PMID- 30112339
TI  - Sequential treatment with alectinib in crizotinib-resistant non-small-cell lung
      cancer.

PMID- 30112340
TI  - Adult Burkitt lymphoma: An institutional experience with a uniform chemotherapy
      protocol.
AB  - Background: Burkitt lymphoma (BL) is treated with short, intensive, noncross
      resistant multidrug chemotherapy regimens. The management of this aggressive
      lymphoma is a challenge in our resource-limited setting, and the published data
      from India is scarce. Aim: This retrospective study aims to evaluate the clinical
      features and treatment outcomes in adult patients with BL treated with uniform
      chemotherapy, cyclophosphamide, vincristine, doxorubicin, methotrexate,
      ifosfamide, etoposide, cytarabine (CODOX-M/IVAC) protocol (+/- Rituximab).
      Materials and Methods: The hospital records between 2011 and 2017 were reviewed
      to identify adult patients (age >=18 years) who were treated with CODOX-M/IVAC
      protocol (+/- Rituximab). The demographic and clinical details, treatment,
      outcomes, and toxicity were recorded from the patient's prospectively maintained
      case records. Results: Eighteen patients were included in this study. The median
      age was 38 years with male:female ratio 3.5:1. The majority of patients were high
      risk (14/18). All patients had extranodal site of involvement. The treatment
      completion rate was 83.3%. The overall response rate = 77.8% including complete
      response rate = 66.7%. Five patients (27%) had progressive disease on therapy.
      The estimated 2-year overall survival and event-free survival were 73% and 68.4%,
      respectively. The most common toxicity was myelosuppression (grade v3/4
      neutropenia = 88.8%, grade 3/4 thrombocytopenia = 77.7%, and grade 3/4 anemia =
      66.6%), febrile neutropenia was seen in 66.6% cases. Most common nonhematological
      toxicity was mucositis (grd3/4 = 33.3%). No toxic death was seen. Conclusion:
      This one of the first retrospective analyses of treatment outcomes from India
      suggests that our patients are demographically and clinically similar to the
      western counterpart. The treatment completion rate is high despite significant
      toxicity. BL has a good outcome if treated adequately.

PMID- 30112341
TI  - Diffuse large B-cell lymphoma: An institutional analysis.
AB  - Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of
      non-Hodgkin's lymphoma. We conducted a retrospective study to analyze the
      clinicopathological characteristics, cell of origin, response to therapy, and the
      outcome of patients with DLBCL. Materials and Methods: This was a retrospective
      study which included all patients with DLBCL registered at our center, between
      May 1, 2013, and July 31, 2015. The data regarding demography, clinical
      presentation, histopathology, stage, prognostic index, treatment, and treatment
      related outcome were collected from prospectively maintained clinical case
      records of the patients. Results: In the study, we included 267 patients. The
      median age is 49 (20-81) years with male: female ratio of 2:1. B symptoms were
      seen in 124 (45%) of patients. Early Stages (I and II) were seen in 130 (52%)
      patients, while advanced Stages (III and 1V) were seen in 119 (48%) patients.
      Bulky disease (>7.5 cm) was seen in 30% of cases, and bone marrow was involved in
      12%. Extranodal involvement is present in 35% of cases. Cell of origin data was
      available in 160 (60%) of cases, of which 88 (55%) were germinal center and 72
      (45%) were activated B cell in origin. The distribution according to the
      international prognostic index (IPI) was as follows: low risk 40%, intermediate
      risk 45%, and high risk in 15%. Rituximab was used in 45% of cases. The overall
      response rate was 84% with a complete response (CR) rate of 70.5%. The CR rates
      were better with RCHOP compared with CHOP (77% vs. 61.5%, P = 0.001) and good
      risk IPI (83.3% vs. 65.2%, P < 0.001) compared with intermediate- and high-risk
      IPI. Median follow-up period was 24 months, and 2-year event-free survival (EFS)
      was 70%. The presence of B symptoms, high IPI, failure to attain CR, poor PS, and
      nonrituximab-based chemotherapy were significantly associated with lower EFS.
      Conclusions: This is the first study from India, which investigated the impact of
      chemotherapy with or without rituximab in context of cell of origin. Adding
      rituximab to CHOP showed better response rate and EFS irrespective of cell of
      origin.

PMID- 30112342
TI  - Patterns of epidermal growth factor receptor testing across 111 tertiary care
      centers in India: Result of a questionnaire-based survey.
AB  - Background: We conducted a survey of 111 medical oncologists across India to
      understand the current pattern of epidermal growth factor receptor (EGFR)
      mutation testing at their respective centers. Methods: Medical oncologists from
      111 institutes across India were interviewed face to face using a structured
      questionnaire. They were divided into two groups - Group 1 with in-house EGFR
      testing and Group 2 who send samples to central/commercial laboratories outside
      their institutions. Answers of the two groups were analyzed to see the prevailing
      patterns of EGFR testing and differences between the two groups if any. Results:
      Ninety-five percent (105/111) of medical oncologists recommended testing for EGFR
      mutations in patients with adenocarcinoma histology and 40% (44/111) recommended
      EGFR testing in squamous cell histology. The average time duration to get EGFR
      test results was 10 days in Group 1 centers versus 18 days in Group 2 centers.
      Ninety-six percent (106/111) of the medical oncologists from Group 1 centers
      requested for factoring additional sample for biomarker testing compared to 69%
      (77/111) of the oncologists from Group 2 centers. Sixty-nine percent (77/111) of
      medical oncologists in Group 1 centers would prefer to wait for the test results
      before initiating treatment compared to 46% (51/111) in Group 2. EGFR tyrosine
      kinase inhibitors were used in only approximately 60% of patients with diagnosed
      EGFR mutation in the first line. For patients in whom chemotherapy was initiated
      while waiting for test results, 50% (56/111) of medical oncologists would prefer
      to complete 4-6 cycles before switching to targeted therapy. At the time of
      progression, rebiopsy was possible in approximately 25% of the patients.
      Conclusions: Turnaround time for molecular testing should improve so that
      eligible patients can benefit from targeted therapies in the first line. There is
      a need to increase the awareness among pulmonologists, oncologists, and
      interventional radiologists regarding the importance of adequate samples required
      for molecular tests.

PMID- 30112345
TI  - Excellent response of solifenacin in chemotherapy-induced hemorrhagic cystitis in
      a child with non-Hodgkin's lymphoma.

PMID- 30112343
TI  - Clinical profile and treatment outcomes of metastatic neuroendocrine carcinoma: A
      single institution experience.
AB  - Background: Neuroendocrine carcinoma (NEC) is a rare tumor arising from the
      diffuse neuroendocrine system. Most of these present in the advanced stage and
      palliative chemotherapy remains the only option. The prognosis remains poor with
      the standard chemotherapy regimen of platinum and etoposide (EP) providing modest
      survival benefit. Methods: The study was done for 3 years at a tertiary cancer
      center in South India. Patients with a diagnosis of metastatic NEC were analyzed
      for clinical and pathological characteristics. The treatment outcomes and
      prognostic factors were evaluated using appropriate statistical test. Results: A
      total of 114 patients of metastatic NEC satisfied the inclusion criteria and were
      analyzed. Gastrointestinal including hepatobiliary tract (33%) was the most
      common site of primary disease followed by lung (26%), genitourinary (15%), head
      and neck (14%), and unknown primary (9%). On analysis of pattern of metastasis,
      liver (65%) was the most common site followed by bone (54%) and lung (42%). The
      median overall survival was 11 months with a statistically significant difference
      between pulmonary and extrapulmonary disease (8 vs. 13 months; P = 0.003). Ki67%
      value was strongly associated with prognosis (hazard ratio 0.517, 95% confidence
      interval; 0.318-0.840, P = 0.008) whereas age, sex, and lactate dehydrogenase
      level did not show any relation with survival. Conclusion: The outcome of
      advanced NEC with standard chemotherapy remains poor. Larger studies with other
      therapeutic and novel agents are warranted to improve the treatment outcomes.

PMID- 30112346
TI  - Long-term survival outcomes of technically unresectable carcinoma maxilla
      postinduction chemotherapy.

PMID- 30112344
TI  - Palliative care and end-of-life measure outcomes: Experience of a tertiary care
      institute from South India.
AB  - Introduction: Desisting from disease directed treatment in the past weeks of life
      is a quality criterion in oncology service. Patients with advanced cancer have
      unrealistic expectations from chemotherapy and hold on to it as a great source of
      hope. Many oncologists continue futile and unnecessary treatments, instead of
      conveying to the patients the lack of benefit, resulting in delayed referral for
      palliative care (PC). Materials and Methods: This is a retrospective analysis of
      case records from June 2014 to December 2015. The primary objective was to study,
      how far back in time terminally ill cancer patients received definitive cancer
      directed therapy (DCDT). Apart from patient demographics, the diagnosis, stage,
      and details of DCDT, and death were captured. PC referral data were recorded.
      DCDT to death was taken as treatment-free interval (TFI). Analysis was performed
      using IBM SPSS Statistics for Windows, Version 20. Results: A total of 292 case
      records were evaluated. Seventy-three had inadequate treatment details. Hence,
      219 records were analyzed. PC referral was done in 78.5% of patients. Only best
      supportive care (BSC) without any DCDT was given in 27 patients. The most common
      reason for BSC was a poor performance status in 92.5%. The median time from PC
      referral till death was 43.5 days (range: 1-518 days). Chemotherapy was the most
      common DCDT in 52.9% of patients. The median time from DCDT and death was 49 days
      (range: 0-359 days). Cervical and ovarian cancers patients had the longest TFI;
      shortest in unknown primary. Most patients died at home (70.4%). Patients
      receiving PC preferred home or hospice as place of death. Of the 80 patients
      given hospice care, 39 (36.5%) died in the hospice. Conclusion: While DCDT needs
      to be started at the right time, it should also be discontinued when futile.
      Early involvement of the PC team, even while patients are on DCDT makes the
      transition smoother and more meaningful.

PMID- 30112347
TI  - Strategies to maintain Korea's animal rabies non-occurrence status.
AB  - Endemic animal rabies causes >99% of all human rabies cases; elimination of
      animal rabies reduces the rate of human infections. The most recent animal rabies
      cases in the Gangwon and Gyeonggi provinces of Korea occurred in November 2012
      and February 2013, respectively. Here we explore ways to ensure that Korea
      remains animal rabies non-occurrence. The government must prevent rabies
      recurrence by vaccinating dogs, distributing bait vaccine in regions with a high
      rabies risk, performing laboratory-based surveillance, preventing the flow of
      rabies-suspect animals from neighboring countries, and enhancing border
      quarantine. As has already been shown in several developed countries, careful and
      ongoing rabies control will allow Korea to remain animal rabies-free.

PMID- 30112349
TI  - Immunogenicity of a bivalent killed thimerosal-free oral cholera vaccine,
      Euvichol, in an animal model.
AB  - Purpose: An oral cholera vaccine (OCV), Euvichol, with thimerosal (TM) as
      preservative, was prequalified by the World Health Organization (WHO) in 2015. In
      recent years, public health services and regulatory bodies recommended to
      eliminate TM in vaccines due to theoretical safety concerns. In this study, we
      examined whether TM-free Euvichol induces comparable immunogenicity to its TM
      containing formulation in animal model. Materials and Methods: To evaluate and
      compare the immunogenicity of the two variations of OCV, mice were immunized with
      TM-free or TM-containing Euvichol twice at 2-week interval by intranasal or oral
      route. One week after the last immunization, mice were challenged with Vibrio
      cholerae O1 and daily monitored to examine the protective immunity against
      cholera infection. In addition, serum samples were obtained from mice to measure
      vibriocidal activity and vaccine-specific IgG, IgM, and IgA antibodies using
      vibriocidal assay and enzyme-linked immunosorbent assay, respectively. Results:
      No significant difference in immunogenicity, including vibriocidal activity and
      vaccine-specific IgG, IgM, and IgA in serum, was observed between mice groups
      administered with TM-free and -containing Euvichol, regardless of immunization
      route. However, intranasally immunized mice elicited higher levels of serum
      antibodies than those immunized via oral route. Moreover, intranasal immunization
      completely protected mice against V. cholerae challenge but not oral
      immunization. There was no significant difference in protection between two
      Euvichol variations. Conclusion: These results suggested that TM-free Euvichol
      could provide comparable immunogenicity to the WHO prequalified Euvichol
      containing TM as it was later confirmed in a clinical study. The pulmonary mouse
      cholera model can be considered useful to examine in vivo the potency of OCVs.

PMID- 30112350
TI  - Evaluation of EZplex MTBC/NTM Real-Time PCR kit: diagnostic accuracy and efficacy
      in vaccination.
AB  - Purpose: Tuberculosis (TB) is mainly caused by Mycobacterium tuberculosis, which
      is a pathogenic mycobacterial species grouped under Mycobacterium tuberculosis
      complex (MTBC) with four other pathogenic mycobacterial species. The mycobacteria
      not included in MTBC are known as nontuberculous mycobacteria (NTM), and cause
      several pulmonary diseases including pneumonia. Currently, NTM occurrences in TB
      suspected respiratory specimens have increased, due to which, precise detection
      of MTBC and NTM is considered critical for the diagnosis and vaccination of TB.
      Among the various methods available, real-time PCR is frequently adopted for
      MTBC/NTM detection due to its rapidness, accuracy, and ease of handling. In this
      study, we evaluated a new real-time PCR kit for analytical and clinical
      performance on sputum, bronchial washing, and culture specimens. Materials and
      Methods: For assessing its analytical performance, limit of detection (LOD),
      reactivity, and repeatability test were performed using DNA samples. To evaluate
      clinical performance, 612 samples were collected and clinically tested at a
      tertiary hospital. Results: LOD was confirmed as 0.584 copies/uL for MTBC and
      47.836 copies/uL for NTM by probit analysis (95% positive). For the reactivity
      test, all intended strains were detected and, in the repeatability test, stable
      and steady results were confirmed with coefficient of variation ranging from 0.36
      to 1.59. For the clinical test, sensitivity and specificity were 98.6%-100% and
      98.8%-100% for MTBC and NTM, respectively. Conclusion: The results proved the
      usefulness of the kit in TB diagnosis. Furthermore, it could be adopted for the
      assessment of vaccine efficacy.

PMID- 30112348
TI  - Recent progress in microneme-based vaccines development against Toxoplasma
      gondii.
AB  - Toxoplasmosis is a cosmopolitan zoonotic disease, which infect several warm
      blooded mammals. More than one-third of the human population are seropositive
      worldwide. Due to the high seroprevalence of Toxoplasma gondii infection
      worldwide, the resulting clinical, mental, and economical complications, as well
      as incapability of current drugs in the elimination of parasites within tissue
      cysts, the development of a vaccine against T. gondii would be critical. In the
      past decades, valuable advances have been achieved in order to identification of
      vaccine candidates against T. gondii infection. Microneme proteins (MICs)
      secreted by the micronemes play a critical role in the initial stages of host
      cell invasion by parasites. In this review, we have summarized the recent
      progress for MIC-based vaccines development, such as DNA vaccines, recombinant
      protein vaccines, vaccines based on live-attenuated vectors, and prime-boost
      strategy in different mouse models. In conclusion, the use of live-attenuated
      vectors as vehicles to deliver and express the target gene and prime-boost
      regimens showed excellent outcomes in the development of vaccines against
      toxoplasmosis, which need more attention in the future studies.

PMID- 30112351
TI  - Purification and characterization of monoclonal IgG antibodies recognizing Ebola
      virus glycoprotein.
AB  - Purpose: The goal of this study was to purify and characterize Ebola virus
      glycoprotein (GP)-specific IgG antibodies from hybridoma clones. Materials and
      Methods: For hybridoma production, mice were injected by intramuscular
      electroporation with GP DNA vaccines, and boosted with GP vaccines. The spleen
      cells were used for producing GP-specific hybridoma. Enzyme-linked immunosorbent
      assay, Western blot assay, flow cytometry, and virus-neutralizing assay were used
      to test the ability of monoclonal IgG antibodies to recognize GP and neutralize
      Ebola virus. Results: Twelve hybridomas, the cell supernatants of which displayed
      GP-binding activity by enzyme-linked immunosorbent assay and the presence of both
      IgG heavy and light chains by Western blot assay, were chosen as a possible IgG
      producer. Among these, five clones (C36-1, D11-3, D12-1, D34-2, and E140-2) were
      identified to secrete monoclonal IgG antibodies. When the monoclonal IgG
      antibodies from the 5 clones were tested for their antigen specificity, they
      recognized GP in an antigen-specific and IgG dose-dependent manner. They remained
      reactive to GP at the lowest tested concentrations (1.953-7.8 ng/mL). In
      particular, IgG antibodies from clones D11-3, D12-1, and E140-2 recognized the
      native forms of GP expressed on the cell surface. These antibodies were
      identified as IgG1, IgG2a, or IgG2b kappa types and appeared to recognize the
      native forms of GP, but not the denatured forms of GP, as determined by Western
      blot assay. Despite their GP-binding activity, none of the IgG antibodies
      neutralized Ebola virus infection in vitro, suggesting that these antibodies are
      unable to neutralize Ebola virus infection. Conclusion: This study shows that the
      purified IgG antibodies from 5 clones (C36-1, D11-3, D12-1, D34-2, and E140-2)
      possess GP-binding activity but not Ebola virus-neutralizing activity.

PMID- 30112352
TI  - Development of dual reporter imaging system for Francisella tularensis to monitor
      the spatio-temporal pathogenesis and vaccine efficacy.
AB  - Purpose: Study on the pathogen and the pathogen-related disease require the
      information at both cellular and organism level. However, lack of appropriate
      high-quality antibodies and the difference between the experimental animal models
      make it difficult to analyze in vivo mechanism of pathogen-related diseases. For
      more reliable research on the infection and immune-response of pathogen-related
      diseases, accurate analysis is essential to provide spatiotemporal information of
      pathogens and immune activity to avoid false-positive or mis-interpretations. In
      this regards, we have developed a method for tracking Francisella tularensis in
      the animal model without using the specific antibodies for the F. tularensis.
      Materials and Methods: A dual reporter plasmid using GFP-Lux with putative
      bacterioferritin promoter (pBfr) was constructed and transformed to F. tularensis
      live vaccine strain to generate F. tularensis LVS (FtLVS)-GFP-Lux for both
      fluorescence and bioluminescence imaging. For vaccination to F. tularensis
      infection, FtLVS and lipopolysaccharide (LPS) from FtLVS were used. Results: We
      visualized the bacterial replication of F. tularensis in the cells using
      fluorescence and bioluminescence imaging, and traced the spatio-temporal process
      of F. tularensis pathogenesis in mice. Vaccination with LPS purified from FtLVS
      greatly reduced the bacterial replication of FtLVS in animal model, and the
      effect of vaccination was also successfully monitored with in vivo imaging.
      Conclusion: We successfully established dual reporter labeled F. tularensis for
      cellular and whole body imaging. Our simple and integrated imaging analysis
      system would provide useful information for in vivo analysis of F. tularensis
      infection as well as in vitro experiments, which have not been fully explained
      yet with various technical problems.

PMID- 30112353
TI  - Genetic identification and serological evaluation of commercial inactivated foot
      and-mouth disease virus vaccine in pigs.
AB  - Vaccination is considered a frequently used tool to prevent and control foot-and
      mouth disease (FMD). However, the effectiveness of conventional FMD virus (FMDV)
      vaccines in pigs has been controversial because the massive prophylactic
      vaccination could not elicit proper immune response nor prevent the broad spread
      of FMD outbreak, mainly in pig farms, in South Korea during outbreaks of 2014. In
      addition, there has been little information on the efficacy of inactivated, high
      potency, multivalent, oil-based FMDV vaccine in pigs, because an evaluation of
      FMDV vaccines had been mainly carried out using cattle. In this study, we
      evaluated the genetic identification of commercial inactivated FMDV vaccine and
      monitored the immune responses in pigs under the field condition. Results implied
      that it contained three different serotypes with a high level of antigen payload.
      However, serological results showed low mean percentage of inhibition, and
      positive rate reached its peak at 6-week post-vaccination, indicating current
      FMDV vaccine need to improve for a prophylactic vaccination policy in pigs.
      Therefore, there is an imperative need to develop FMDV vaccine that can provide
      rapid and long-lasting protective immunity in pigs.

PMID- 30112354
TI  - Organoid as a culture system for viral vaccine strains.
AB  - Organoid is an in vitro multicellular form mimicking in vivo organ. Its
      similarity to human organ including cellular organization, molecular expression
      patterns, as well as genetic signatures enables to study the characteristics of
      infectious agents and host-pathogen interaction. For the features of organoid,
      this system also can be potentially used to cultivate currently uncultivable
      viruses of vaccine candidates. This paper will briefly describe problems in the
      current culture system for virus production and the possibility of organoid as
      culture system for viral vaccine and their current limitations that should be
      solved to meet the goal.

PMID- 30112355
TI  - Immunohistochemical Coexpression of Epithelial Cell Adhesion Molecule and Alpha
      Fetoprotein in Hepatocellular Carcinoma.
AB  - Background and Aim: The epithelial cell adhesion molecule (EpCAM) has been
      proposed as a marker for cancer stem cells in human hepatocellular carcinoma
      (HCC) as well as in the development of novel target therapies. This study aimed
      to investigate the immunohistochemical expression of EpCAM and alpha-fetoprotein
      (AFP) in HCC patients and their association with clinicopathological
      characteristics. Methods: This study included Child-Pugh A HCC patients
      undergoing curative surgical resection. Results: A significant difference was
      observed in the ratio between the different phenotypes (p = 0.002), identifying
      12 (29.3%) EPCAM positive tumors and 29 (70.7%) negative tumors. EpCAM+
      expression was associated with AFP + (OR = 12.5, 95% CI, 1.9-84.1, p<0.001). In
      univariate analysis, a significant association was observed between AFP+ and
      EPCAM+ and the serum AFP level. A diameter of <= 5 cm was associated with EPCAM+,
      while angiolymphatic invasion was associated with APF+. In a multivariate
      analysis, only tumors of <= 5 cm were significantly associated with EpCAM+ (OR =
      8.7; 95%CI, 1.27-100.0; p = 0.022). The overall survival rate was 74.9%, 69.4%,
      69.4%, and 53.5% at 12, 24, 36, and 48 months, respectively. Conclusion: A
      considerable number of patients with EpCAM+ HCC would benefit from a specific
      target therapy.

PMID- 30112356
TI  - Functional Polymorphisms in IRAKs Are Related to Hepatocellular Carcinoma Risk in
      Chinese Population.
AB  - Background: Interleukin 1 receptor associated kinases (IRAKs) play a central role
      in TLR signaling pathway. Scarce literature has investigated the association of
      potential functional genetic variants of IRAKs with Hepatitis B Virus- (HBV-)
      related hepatocellular carcinoma (HCC). Methods: A case-control study with 1,538
      HBV-positive HCC patients and 1,465 chronic HBV carriers was conducted to
      evaluate the effects of common missense variants of IRAK family members on HCC.
      Proliferation assays and real-time polymerase chain reactions were carried out to
      evaluate the functions. Multivariable adjusted logistic regression was adopted to
      estimate effect size and identify risk factors. Results: Association analysis
      indicated that rs4251545 A allele of IRAK4 (p.Ala428Thr) was positively
      associated with HBV-related HCC risk (OR = 1.30, 95% CI: 1.09-1.54, P = 0.003).
      Functional annotation indicated that rs4251545 reduced its own expression in
      liver (P = 0.031). Further molecular functional analysis detected that rs4251545
      increased the proliferation rate of L02 cells (P < 0.05). Meanwhile, rs4251545
      reduced mRNA expressions of IL-6, IL-8, CXCL-1, and CXCL-2 in L02 cells (P <
      0.01). Conclusion: rs4251545 of IRAK4 (p.Ala428Thr) modified the susceptibility
      to HBV-related HCC via increased proliferation rate and reduced production of
      inflammatory cytokines and chemokines. Further well-designed experiments are
      warranted to validate our findings.

PMID- 30112357
TI  - Identification of 170 New Long Noncoding RNAs in Schistosoma mansoni.
AB  - Long noncoding RNAs (lncRNAs) are transcripts generally longer than 200
      nucleotides with no or poor protein coding potential, and most of their functions
      are also poorly characterized. Recently, an increasing number of studies have
      shown that lncRNAs can be involved in various critical biological processes such
      as organism development or cancer progression. Little, however, is known about
      their effects in helminths parasites, such as Schistosoma mansoni. Here, we
      present a computational pipeline to identify and characterize lncRNAs from RNA
      seq data with high confidence from S. mansoni adult worms. Through the
      utilization of different criteria such as genome localization, exon number, gene
      length, and stability, we identified 170 new putative lncRNAs. All novel S.
      mansoni lncRNAs have no conserved synteny including human and mouse. These
      closest protein coding genes were enriched in 10 significant Gene Ontology terms
      related to metabolism, transport, and biosynthesis. Fifteen putative lncRNAs
      showed differential expression, and three displayed sex-specific differential
      expressions in praziquantel sensitive and resistant adult worm couples. Together,
      our method can predict a set of novel lncRNAs from the RNA-seq data. Some lncRNAs
      are shown to be differentially expressed suggesting that those novel lncRNAs can
      be given high priority in further functional studies focused on praziquantel
      resistance.

PMID- 30112358
TI  - Infant Skin Barrier, Structure, and Enzymatic Activity Differ from Those of Adult
      in an East Asian Cohort.
AB  - Skin physiology is dynamically changing over the first years of postnatal life;
      however, ethnic variations are still unclear. The aim of this study was to
      characterize infant skin barrier function, epidermal structure, and desquamation
      related enzymatic activity as compared to that of adult skin in an East Asian
      population. The skin properties of 52 infants (3-24 months) and 27 adults (20-40
      years) were assessed by noninvasive methods at the dorsal forearm and upper inner
      arm. Transepidermal water loss and skin surface conductance values were higher
      and more dispersed for infants compared to adults. Infant skin surface pH was
      slightly lower than adult on the dorsal forearm. The infant SC and viable
      epidermis were thinner compared to adults with differences that were site
      specific. Although the chymotrypsin-like activity for infant skin was comparable
      to adult level, the caseinolytic specific activity was significantly higher for
      the infant cohort. These observations indicate a differently controlled pattern
      of corneocyte desquamation in infants. In conclusion, structural and functional
      differences exist between infant and adult skin in the East Asian population
      pointing to dynamic maturation of the epidermal barrier early in life.

PMID- 30112359
TI  - Apoptotic and Anti-Inflammatory Effects of Eupatorium japonicum Thunb. in
      Rheumatoid Arthritis Fibroblast-Like Synoviocytes.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease
      characterized by synovitis, hyperplasia, and the destruction of bone and
      cartilage. A variety of immunosuppressive biological agents have been developed
      because the pathogenesis of RA is related predominantly to the inflammatory
      response. However, rheumatoid arthritis fibroblast-like synovial cells (RAFLS),
      which are known to play an important role in RA progression, exhibit resistance
      to immunosuppressants through cancer-like properties. In this study, we
      identified a novel therapeutic compound for RA, which reduced inflammation and
      the abnormal proliferation of RAFLS in natural product library made from Korean
      native plants. Eupatorium japonicum Thunb. (EJT) extract, a component of the
      natural product library, most effectively reduced viability through the induction
      of ROS-mediated apoptosis in a dose-dependent manner. In addition, the increased
      ROS induced the expression of ATF4 and CHOP, key players in ER stress-mediated
      apoptosis. Interestingly, EJT extract treatment dose-dependently reduced the
      expression of IL-1beta and the transcription of MMP-9, which were induced by TNF
      alpha treatment, through the inhibition of NF-kappaB and p38 activation.
      Collectively, we found that EJT extract exerted apoptotic effects through
      increases in ROS production and CHOP expression and exerted anti-inflammatory
      effects through the suppression of NF-kappaB activation, IL-1beta expression, and
      MMP-9 transcription.

PMID- 30112362
TI  - A New Surgical Method of U-Shaped Myometrial Excavation and Modified Suture
      Approach with Uterus Preservation for Diffuse Adenomyosis.
AB  - Objective: To evaluate the feasibility, safety, and efficacy of a new surgical
      method of U-shaped myometrial excavation and modified suture approach with uterus
      preservation for diffuse adenomyosis. Methods: From January 2012 to December
      2014, 198 patients with diffuse adenomyosis were surgically treated using this
      novel procedure in Zhengzhou Hua-Shan Hospital. Degree of dysmenorrhea, menstrual
      blood volume, serum CA 125, and uterine size before and at 1 month, 3 months, 6
      months, 12 months, and 24 months after surgery were compared. Results:
      Postoperatively, VAS score of dysmenorrhea, menstrual blood volume, serum CA 125
      level, and uterine size significantly decreased at 1 month, 3 months, 6 months,
      12 months, and 24 months from presurgical levels (all p < .001), but there were
      no differences at the follow-up time points. Two patients recurred at 18 months
      and 23 months after surgery, but both recovered after repeat surgery.
      Interestingly, 2 other patients recrudesced at 10 months and 12 months after
      surgery. In addition, only one patient was found to have a postoperative anaemia
      with fever, conservatively managed without surgery. Conclusion: U-shaped
      myometrial excavation and modified suture approach with uterus preservation is a
      safe and feasible surgical approach to treat diffuse adenomyosis, with favourable
      outcomes.

PMID- 30112361
TI  - Role of MAPKs in HSP70's Protection against Heat Stress-Induced Injury in Rat
      Small Intestine.
AB  - Aim: To evaluate the role of heat shock protein 70 (HSP70) on the MAPK pathway
      activation with quercetin treatment and its protection against small intestine
      impairments of heat stressed rats. Methods: Forty-eight male Sprague-Dawley rats
      aged 6 weeks were randomized to three groups (n=16/group), namely, control (CON),
      heat stress (HS), and heat stress + quercetin (HQ). The experiment lasted for 14
      days with daily 50 min of heat stress treatment (43 degrees C) for the HS and HQ
      groups. Rats of HQ group were intragastrically given 0.5 ml quercetin solution
      (50 mg/kg body weight) before the heat stress treatment. Half of the animals were
      sacrificed on day 7 and the rest on day 14 for tissue sampling. Intestinal
      morphology, small intestine morphology and permeability, protein expression of
      HSP70, phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N
      terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and caspase-3
      activity were examined. Results: Heat stress caused morphological damage to the
      small intestine and increased intestinal permeability. HSP70 expression and MAPK
      activity in the small intestine were increased by heat stress. Inhibition of
      HSP70 by quercetin did not change intestinal permeability compared with the HS
      group but aggravated intestinal injury and affected the activation of MAPKs and
      caspase-3. Conclusions: HSP70 may modulate stress-activated signaling and acts in
      a protective manner via MAPK signaling. Affecting HSP70 protective mechanisms
      could be useful for protection against heat stress-induced injury in rat small
      intestine.

PMID- 30112363
TI  - A Comparative Analysis of Methods for Evaluation of ECG Signal Quality after
      Compression.
AB  - The assessment of ECG signal quality after compression is an essential part of
      the compression process. Compression facilitates the signal archiving, speeds up
      signal transmission, and reduces the energy consumption. Conversely, lossy
      compression distorts the signals. Therefore, it is necessary to express the
      compression performance through both compression efficiency and signal quality.
      This paper provides an overview of objective algorithms for the assessment of
      both ECG signal quality after compression and compression efficiency. In this
      area, there is a lack of standardization, and there is no extensive review as
      such. 40 methods were tested in terms of their suitability for quality
      assessment. For this purpose, the whole CSE database was used. The tested signals
      were compressed using an algorithm based on SPIHT with varying efficiency. As a
      reference, compressed signals were manually assessed by two experts and
      classified into three quality groups. Owing to the experts' classification, we
      determined corresponding ranges of selected quality evaluation methods' values.
      The suitability of the methods for quality assessment was evaluated based on five
      criteria. For the assessment of ECG signal quality after compression, we
      recommend using a combination of these methods: PSim SDNN, QS, SNR1, MSE, PRDN1,
      MAX, STDERR, and WEDD SWT.

PMID- 30112364
TI  - Factors That Predict the Growth of Residual Nonfunctional Pituitary Adenomas:
      Correlations between Relapse and Cell Cycle Markers.
AB  - Introduction: Nonfunctional pituitary adenomas are treated surgically, and even
      partial resection can improve or eliminate clinical symptoms. Notably,
      progression requires further intervention, which presents an increased risk,
      especially in older patients. This study investigated whether the
      histopathological characteristics of nonfunctional adenomas could predict
      recurrence. Materials and Methods: Data were obtained retrospectively from 30
      patients who underwent surgery for the partial resection of pituitary adenomas.
      Remnant tumor growth was observed in 17 patients, while the residual tumor was
      unchanged more than 7 years after surgery in 13 patients. Statistical analysis
      was performed to investigate correlations between remnant tumor progression and
      tumor histopathological findings, including protein expression of p21, p27, p53,
      and Ki-67. Results and Discussion: Remnant tumors that demonstrated regrowth
      showed significantly higher protein expression of p21 and Ki-67. Expression of
      the p53 tumor suppressor was also higher in this group, but the difference was at
      the limit of statistical significance. Conclusion: Tumors with high expression of
      p21 and p53 and with a high Ki-67 index were more likely to show residual
      pituitary adenoma progression. Such cases should undergo frequent radiological
      examination and timely reoperation, and radiosurgery should be considered.

PMID- 30112365
TI  - Corrigendum to "Mesenchymal Stem Cells Attenuate Radiation-Induced Brain Injury
      by Inhibiting Microglia Pyroptosis".
AB  - [This corrects the article DOI: 10.1155/2017/1948985.].

PMID- 30112366
TI  - Permethrin Susceptibility for the Vector Culex tarsalis and a Nuisance Mosquito
      Aedes vexans in an Area Endemic for West Nile Virus.
AB  - In 2016, we compared susceptibility to the insecticide, permethrin, between the
      West Nile virus vector, Culex tarsalis Coquillett, and a major nuisance mosquito,
      Aedes vexans (Meigen), using baseline diagnostic dose and time values determined
      using the CDC bottle bioassay protocol. Mosquitoes were collected in the wild in
      Brookings County, South Dakota, situated in the Northern Great Plains of the USA.
      The determined diagnostic dose and time were then used in 2017 to validate these
      measurements for the same 2 mosquito species, collected at a second location
      within Brookings County. The diagnostic dose was determined for multiple time
      periods and ranged from 27.0 ug/ml at 60 min to 38.4 ug/ml at 30 min. There was
      no significant difference detected in mortality rates between Cx. tarsalis and
      Ae. vexans for any diagnostic time and dose. For practical purposes, mosquitoes
      in 2017 were tested at 38 ug/ml for 30 min; expected mortality rates were 93.38%
      for Cx. tarsalis and 94.93% for Ae. vexans. Actual 2017 mortality rates were
      92.68% for Cx. tarsalis and 96.12% for Ae. vexans, validating the usefulness of
      this baseline at an additional location and year.

PMID- 30112368
TI  - Erratum to "Overhydroxylation of Lysine of Collagen Increases Uterine Fibroids
      Proliferation: Roles of Lysyl Hydroxylases, Lysyl Oxidases, and Matrix
      Metalloproteinases".
AB  - [This corrects the article DOI: 10.1155/2017/5316845.].

PMID- 30112369
TI  - Isolation of a Trypanosome Related to Trypanosoma theileri (Kinetoplastea:
      Trypanosomatidae) from Phlebotomus perfiliewi (Diptera: Psychodidae).
AB  - The Trypanosoma theileri group includes several trypanosome species hardly
      distinguishable due to the lack of discriminating morphological characters.
      Trypanosomes belonging to this group have been isolated from different bovine,
      ovine, and cervids in Europe, Africa, Asia, and Americas. The principal vectors
      of the T. theileri group are considered tabanid flies; however, T. melophagium is
      transmitted exclusively by sheep keds. In 2016, 128 sand flies out of 2,728
      trapped in Valsamoggia municipality, Italy, were individually dissected and an
      unknown trypanosome strain, named TrPhp1, was isolated from a female of the sand
      fly Phlebotomus perfiliewi. Sequence analysis placed this trypanosome in the T.
      theileri group with very high homology to other trypanosomes detected in European
      cervids. This is the first report of the T. theileri group isolation from a sand
      fly, and the possible role of this insect group in the trypanosome transmission
      cycle is discussed. Within the T. theileri group, the phylogenetic analysis
      distinguished several lineages, which, unfortunately, do not correspond with
      their host specificity and their taxonomic status remains ambiguous.

PMID- 30112367
TI  - Levels of Resistance to Pyrethroid among Distinct kdr Alleles in Aedes aegypti
      Laboratory Lines and Frequency of kdr Alleles in 27 Natural Populations from Rio
      de Janeiro, Brazil.
AB  - Background: Several mutations in voltage gated sodium channel (NaV) have been
      identified in Aedes aegypti populations worldwide. However, only few are related
      to knockdown resistance to pyrethroids, most of which with variations in the 1016
      and 1534 NaV sites. In Brazil, at least two NaV alleles are known: NaVR1, with a
      substitution in the 1534 (1016 Val+ + 1534 Ile kdr ) and NaVR2, with
      substitutions in both 1016 and sites (1016Ilekdr + 1534Cys kdr ). There is also
      the duplication in the NaV gene, with one copy carrying the substitution
      Ile1011Met, although its effects on pyrethroid resistance remain to be clarified.
      Our goals in this study were (1) to determine the role of each kdr NaV allele and
      the duplication on pyrethroid resistance and (2) to screen the frequency of the
      kdr alleles in 27 several natural Ae. aegypti populations from the metropolitan
      region of Rio de Janeiro. Methods: Pyrethroid resistance was evaluated by a
      knockdown time (KdT) assay, an adaptation of the WHO test tubes with paper
      impregnated with deltamethrin. We used laboratory-selected Ae. aegypti lineages:
      R1R1 and R2R2 (homozygous for the kdr NaVR1 and NaVR2 alleles, respectively), Dup
      (with duplication in the NaV gene), Rockefeller (the susceptibility reference
      control), and F1 hybrids among them. Genotyping of both 1016 and 1534 NaV sites
      was performed in 811 Ae. aegypti sampled from 27 localities from Rio de Janeiro
      (17), Niteroi (6) and Nova Iguacu (4) cities, Rio de Janeiro State, Brazil, with
      a TaqMan real time PCR approach. Results: The laboratory lineages R1R1, R2R2, and
      R1R2 were the only ones that needed more than 60 minutes to knock down all the
      insects exposed to the pyrethroid, being the KdT R2R2 > R1R2 > R1R1,
      corroborating the recessive nature of the kdr mutations. Frequency of kdr alleles
      NaVR1 and NaVR2 in field-caught mosquitoes varied from 0 to 52% and 43 to 86%,
      respectively, evidencing high levels of "resistant genotypes" (R1R1, R1R2, and
      R2R2), which together summed 60 to 100% in Ae. aegypti populations from Rio de
      Janeiro. Conclusions: The NaVR1 and NaVR2 kdr alleles confer resistance to the
      pyrethroid deltamethrin in homozygotes and R1R2 heterozygotes, being the R2R2
      most resistant genotype. The allele containing duplication in the NaV gene, with
      a mutation in the 1011 site, did not confer resistance under the tested
      conditions. The frequencies of the "resistant genotypes" are elevated in Ae.
      aegypti natural populations from Rio de Janeiro.

PMID- 30112360
TI  - Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and
      Alzheimer's Disease.
AB  - Alzheimer's disease (AD) and multiple sclerosis are major neurodegenerative
      diseases, which are characterized by the accumulation of abnormal pathogenic
      proteins due to oxidative stress, mitochondrial dysfunction, impaired autophagy,
      and pathogens, leading to neurodegeneration and behavioral deficits. Herein, we
      reviewed the utility of plant polyphenols in regulating proliferation and
      differentiation of stem cells for inducing brain self-repair in AD and multiple
      sclerosis. Firstly, we discussed the genetic, physiological, and environmental
      factors involved in the pathophysiology of both the disorders. Next, we reviewed
      various stem cell therapies available and how they have proved useful in animal
      models of AD and multiple sclerosis. Lastly, we discussed how polyphenols utilize
      the potential of stem cells, either complementing their therapeutic effects or
      stimulating endogenous and exogenous neurogenesis, against these diseases. We
      suggest that polyphenols could be a potential candidate for stem cell therapy
      against neurodegenerative disorders.

PMID- 30112370
TI  - Optimal Condition to Create Femoral Tunnel Considering Combined Influence of Knee
      Flexion and Transverse Drill Angle in Anatomical Single-Bundle ACL Reconstruction
      Using Medial Portal Technique: 3D Simulation Study.
AB  - There has been no previous study using three-dimensional (3D) measurement on
      femoral tunnel characteristics according to the combined influence of various
      flexion angles of knee and transverse drill angles in single-bundle ACL
      reconstruction with transportal technique. The purpose of this study was to
      determine optimal condition of knee flexion angle and transverse drill angle to
      create secure femoral tunnel in single-bundle ACL reconstruction with transportal
      technique considering tunnel length, tunnel wall breakage, and graft bending
      angle. This study was conducted using simulation of 3D computed tomography of
      thirty subjects. Three variables of femoral tunnel changed according to combined
      influence of four flexion angles of knee and three transverse drill angles were
      measured: tunnel length, wall breakage, and graft bending angle. There was no
      case of short femoral tunnel less than 25 mm at 120 degrees  and 130 degrees  of
      flexion. There was no case of breakage of femoral tunnel at 120 degrees  of
      flexion with maximum transverse drill angle (MTA) and MTA-10 degrees  and at 130
      degrees  of flexion. Considering effect on graft bending angle, decrease of
      flexion angle and transverse drill angle could be appropriate in creating femoral
      tunnel. Increased flexion angle and transverse drill angle secured femoral tunnel
      having sufficiently long length without wall breakage. However, avoiding
      excessive flexion angle and maximum transverse drill angle could be recommended
      because they tended to cause more acute graft bending angle.

PMID- 30112371
TI  - Correlations between the Visual Apparatus and Dental Occlusion: A Literature
      Review.
AB  - Background: The development of visual functions takes place in the first months
      of postnatal life and is completed around the one year of age. In this period,
      the maturation of the retina and the visual pathways occur, and binocular bonds
      are established at the level of the visual cortex. During this phase and then for
      a few years, a certain plasticity of the visual functions remains, which seem
      therefore susceptible to change both in a pejorative sense (by pathogens) and in
      an improving sense (for example, by therapeutic measures). This plasticity
      involves also the oculomotor system. Due to this plasticity, many researchers
      believe that there are some functional correlations between the visual and the
      stomatognathic apparatus. But the scientific evidence of this statement has not
      been clarified yet. Aim: The purpose of this review is therefore to analyze the
      clinical data in this field and finally to establish their level of evidence.
      Studies have been collected from the main databases, based on keywords. Results:
      The results showed a middle level of evidence since most of the data derive from
      case-control studies and cross-sectional studies. Conclusions: The level of
      evidence allows establishing that there is a correlation between ocular disorders
      (myopia, hyperopia, astigmatism, exophoria, and an unphysiological gait due to
      ocular convergence defects) and dental occlusion, but it is not possible to
      establish the cause-effect relationship. Future studies should be aimed at
      establishing higher levels of evidence (prospective, controlled, and randomized
      studies).

PMID- 30112373
TI  - Optimization of the Cytotoxic Activity of Three Streptomyces Strains Isolated
      from Guaviare River Sediments (Colombia, South America).
AB  - Three Streptomyces strains isolated from Guaviare sediments (Colombia, South
      America) with cytotoxic activity against prostate cancer (PC3), breast cancer
      (MDA-MB-231), and lung cancer (A549) line cells were studied. The present
      investigation reveals the enhancement of the cytotoxic activity evaluating
      different values of pH, carbon sources (sucrose, glucose, xylose, maltose, and
      starch), and nitrogen sources (malt extract, yeast extract, meat extract,
      peptone, and potassium nitrate). Based on the response surface methodology, the
      isolates Streptomyces aburaviensis (73) had the maximum activity for lung cancer
      (IC50= 25.00 +/- 1.86 ppm) with 4% of yeast extract, 3% of starch, and a pH value
      of 7. Streptomyces gramineus (386) had the maximum activity against prostate
      cancer (IC50= 6.14 +/- 2.07 ppm) with 5% of malt extract, 3% of glucose, and a pH
      value of 6. Finally, Streptomyces psammoticus (519) had the maximum activity
      against breast cancer (IC50= 35.53 +/- 2.71 ppm) with 1% of yeast extract, 4% of
      starch, and a pH 8. The results suggest that the ethyl acetate extracts from
      isolates Streptomyces aburaviensis (73), Streptomyces gramineus (386), and
      Streptomyces psammoticus (519) have a potential for use in pharmaceuticals as
      cytotoxic agents.

PMID- 30112372
TI  - The Impact of Vitamin D Deficiency on Retinopathy and Hearing Loss among Type 2
      Diabetic Patients.
AB  - Aim: The current study was aiming to investigate the relation between vitamin D,
      retinopathy, and hearing loss among type 2 diabetes mellitus (T2DM) patients.
      Methods: Cross-sectional study carried on 638 subjects aged between 20 and 60
      years who visited the Endocrinology, Ophthalmology, and ENT Outpatient Clinics of
      the Medipol Hospital during the period from March 2016 to May 2017. Two
      audiometers Grason Stadler GSI 61 and Interacoustics AC40 Clinical audiometer
      were used to evaluate the hearing loss. Risk factors for diabetic retinopathy
      were evaluated, including age, sex, diabetes duration, glycated hemoglobin
      (HbA1c), hypertension, and lipid profiles. Results: The mean age (+/- SD, in
      years) for retinopathy with hearing loss versus normal subjects was 47.7 +/-10.2
      versus 48.5+/-9.1. The associated risk factors were significantly higher in T2DM
      with hearing loss, hypertension (32.6% versus 15.7%), tinnitus (40.0% versus
      18.0%), vertigo (59.7% versus 26.8%), and headache (54.9% versus 45.3%), than in
      normal hearing diabetes. There were statistically significant differences between
      hearing impairment versus normal hearing for vitamin D [19.40+/-9.71 ng/ml versus
      22.67+/-9.28 ng/ml; p<0.001], calcium, magnesium, phosphorous, cholesterol, HDL
      C, LDL-C, albumin, systolic blood pressure [131.70+/-9.25 Hg versus 127.73+/
      11.98 Hg], diastolic blood pressure [82.20+/-8.60 mm Hg versus 79.80+/-8.20 mm
      Hg], and microalbuminuria. Multivariate logistic regression analysis revealed
      that variables such as vertigo, duration of DM, mobile/I pad phone, vitamin D
      deficiency, sleeping disturbance, headache, frequently TV watching, tinnitus,
      cigarette smokers, and hypertension were considered at higher risk as a
      predictors of retinopathy with hearing loss among diabetic patients. Conclusion:
      Vitamin D deficiency is considered as a risk factor for diabetic retinopathy and
      hearing loss among diabetic patients. Meanwhile, hyperglycemia could be
      considered as a modifiable risk factor for diabetic retinopathy; tight glycemic
      control may be the most effective and important therapy for improving quality of
      life and substantially reducing the incidence of retinopathy and in T2DM
      patients.

PMID- 30112374
TI  - Incidence of Intestinal Infectious Diseases due to Protozoa and Bacteria in
      Mexico: Analysis of National Surveillance Records from 2003 to 2012.
AB  - Background: According to national epidemiological surveillance records, in Mexico
      six intestinal infectious diseases (IID) are among the top infectious
      communicable diseases. However, their incidence, relative importance, and spatial
      patterns have not been studied in detail. Aims: We examine the epidemiology of
      IID due to bacteria and protozoa to identify which diseases are most important at
      two spatial scales, what is their integrated importance locally, and how their
      incidence correlates with Human Development Index (HDI). Methods: We retrieved
      yearly number of new cases of eight IID from the national epidemiological
      morbidity report from 2003 to 2012 at the national level, by state, and to assess
      such information at a higher spatial resolution we included the municipalities
      for Mexico City. However, no comparisons were made to other municipalities due to
      unavailability of data. We compared incidence, obtained the disease-specific
      relative importance, and inspected spatial patterns for the integrated incidence.
      Finally, we tested whether HDI is correlated with incidence. Results: We found
      that, except for two diseases, the relative importance of the other six IID
      contrasted not only between the national level and Mexico City, but also among
      states and municipalities in Mexico City. Besides, at both scales the
      distribution of the incidence showed disease-specific spatial patterns. Finally,
      there was a lack of consistent correlation between HDI and individual IID at both
      scales. Conclusion: Our results emphasize the need for local disease-focused
      selective models for control and prevention of IID. The maps displaying our
      analyses of epidemiological similarities may be used in orienting such effort.

PMID- 30112375
TI  - Carotid Arterial Stiffness and Hemodynamic Responses to Acute Cycling
      Intervention at Different Times during 12-Week Supervised Exercise Training
      Period.
AB  - This paper studied the alterations in arterial stiffness and hemodynamic
      responses during resting state and immediately following acute cycling
      intervention at different times across 12-week supervised exercise training.
      Twenty-six sedentary young males participated in the exercise training program at
      moderate intensity. Arterial stiffness and hemodynamic variables of the right
      common carotid artery were measured and computed during resting state and
      immediately following acute cycling intervention at weeks 0, 4, 8, and 12. Across
      the 12-week exercise training, carotid arterial stiffness was decreased at weeks
      8 and 12 and hemodynamic variables were improved at week 12 during resting state.
      In response to acute cycling intervention, carotid arterial stiffness exhibited
      an acute increase foremost at 8 weeks, and arterial maximal and mean diameters
      showed acute decreases at weeks 0 and 4. Despite significant differences in
      arterial stiffness and hemodynamic variables between resting state and
      immediately after acute intervention for each time period, these differences
      presented a progressive decrease across the 12-week exercise training. In
      conclusion, long-term exercise training not only improved carotid arterial
      stiffness and hemodynamic alterations when at rest but also negated the acute
      responses of carotid arterial stiffness and hemodynamic variables to acute
      cycling intervention.

PMID- 30112377
TI  - Why Do Some Ethiopian Women Give Birth at Home after Receiving Antenatal Care?
      Phenomenological Study.
AB  - Background: In Ethiopia, majority (62%) of pregnant women receive at least one
      antenatal follow-up, yet only 26% give birth in health facility. Understanding
      factors underlying this high uptake of antenatal care and low institutional
      delivery service is critical. Women had antenatal care follow-up means; by
      default they have access to health facilities. Thus, why do some give birth at
      home even after receiving antenatal care? Methods. Fourteen key informant
      interviews and six focused group discussions were held among purposively selected
      women who gave birth in the last 12 months without skilled attendance after
      receiving antenatal care. The study explored women's perspectives on maternity
      care, care providers, and factors that influence place of delivery.
      Interpretative phenomenological analysis was used to examine various behaviors
      and beliefs of respondents. Results: Study participants described range of
      experiences and beliefs that made them give birth at home after receiving
      antenatal care at health facilities. Four themes emerged from women's
      description: poor counseling during antenatal care service, traditions, early
      pregnancy symptoms, and lack of planning in advance for childbirth. Conclusion:
      Poor counseling during antenatal care is deterring women from seeking skilled
      attendance at birth. Thus, healthcare providers need to stress necessity of
      facility based delivery care during antenatal follow-up counseling.

PMID- 30112376
TI  - Impalpable Testis: Evaluation of Diagnostic and Treatment Procedures and Our
      Treatment Protocol.
AB  - Introduction: The aim of this study is to present our treatment protocol for
      impalpable testis. Material and Methods: In a retrospective study we analyzed
      clinical data including diagnostic procedures, intraoperative findings, final
      diagnosis, treatment modality, and outcome of patients with impalpable testis who
      underwent surgery from January 2010 until December 2015. Results: Ninety-one
      patients were admitted under the diagnosis of impalpable testis. In 39 patients
      ultrasound detected testis in the inguinal canal and orchidopexy was done. In 25
      patients (48.08%) laparoscopy showed the entrance of the spermatic cord into the
      inguinal canal. Open exploration of the inguinal canal was done, testicular
      remnant removed, and appropriate testicular prosthesis implanted. Twenty patients
      (20/52) underwent orchidopexy of the abdominal testis (46.51%), 4 of which
      underwent Fowler-Stevens procedure in two stages, and in 16 patients deliberation
      of the testis and spermatic cord was sufficient to place the testis into the
      scrotum. Conclusions: Excision of the testicular nubbin is highly recommendable,
      as well as implantation of the testicular prosthesis at the time of orchiectomy.

PMID- 30112378
TI  - OCT4 Potentiates Radio-Resistance and Migration Activity of Rectal Cancer Cells
      by Improving Epithelial-Mesenchymal Transition in a ZEB1 Dependent Manner.
AB  - Radiotherapy is an important strategy for rectal cancer patient treatment.
      However, the efficiency of radiation is usually poor, especially in patients with
      advanced stage rectal cancer due to the radio-resistance developed. At the
      present study, OCT4 was found to play a critical role in radio-resistance
      development in human rectal cancer cells by improving the epithelial-mesenchymal
      transition process (EMT). Endogenous OCT4 expression could confer resistant
      phonotype on human rectal cancer cells, which was supported by the data from
      clonogenic forming assay and cell cycle arrest recovering experiment. EMT related
      transcription factor ZEB1 might take part in the radio-resistance induced by
      OCT4, as its expression could be upregulated by OCT4 and its silence could
      reverse the OCT4 induced resistance to radiation in SW480 cells. More
      interestingly, CHK1 was also upregulated in OCT4/ZEB1 dependent manner conferring
      stronger DNA damage repair activity on cancer cells, which might explain the
      underlying mechanisms why OCT4/ZEB1 axis could promote the resistance of human
      rectal cancer cell to radiation. Taken together, our results provided a novel
      mechanism for radio-resistance development in human rectal cancer cells and a new
      target to overcome this resistance.

PMID- 30112380
TI  - Characterization of Positional Distribution of Fatty Acids and Triacylglycerol
      Molecular Compositions of Marine Fish Oils Rich in Omega-3 Polyunsaturated Fatty
      Acids.
AB  - The regiospecific characteristics of n-3 polyunsaturated fatty acids (PUFAs) in
      triacylglycerol (TAG) significantly affect the physicochemical and physiological
      properties of marine fish oils. In this study, the TAG molecular species
      composition and positional distributions of fatty acids were investigated in
      three marine fish species rich in omega-3 PUFAs (anchovy, tuna, and salmon). The
      regiospecific distribution of the fatty acids was measured with the
      allylmagnesium bromide (AMB) degradation method. The TAG compositions were
      analyzed with HPLC and the TAG molecular species were identified with APCI/MS.
      DHA was preferentially distributed at the sn-2 position of TAG, whereas EPA was
      evenly distributed along the glycerol backbone. The combinations of FAs, DDO,
      EOP, EPS, DSS, OOS, and PPS were the predominant TAG molecular species, and OOP,
      DOS, and DPoPo were the characteristic TAG molecules in the anchovy, salmon, and
      tuna, respectively. These data can be used to distinguish other marine fish
      species. The TAG composition categorized by TCN and ECN showed well-structured
      distributions, with double or triple peaks. These findings should greatly extend
      the use of marine fish oils in food production and may significantly affect the
      future development of the fish oil industry.

PMID- 30112379
TI  - The Impact of Artesunate-Amodiaquine on Schistosoma mansoni Infection among
      Children Infected by Plasmodium in Rural Area of Lemfu, Kongo Central, Democratic
      Republic of the Congo.
AB  - Background: Malaria and schistosomiasis remain life-threatening public health
      problems in sub-Saharan Africa. The infection pattern related to age indicates
      that preschool and school-age children are at the highest risk of malaria and
      schistosomiasis. Both parasitic infections, separately or combined, may have
      negative impacts on the haemoglobin concentration levels. The existing data
      revealed that artemisinin derivatives commonly used to cure malaria present also
      in antischistosomal activities. The current study investigated the impact of
      Artesunate-Amodiaquine (AS-AQ) on schistosomiasis when administered to treat
      malaria in rural area of Lemfu, DRC. Methodology: A prospective longitudinal
      study including 171 coinfected children screened for anaemia, Schistosoma
      mansoni, and Plasmodium falciparum infections. The egg reduction rate and
      haemoglobin concentration were assessed four weeks after the treatment with AS
      AQ, of all coinfected children of this series. Results: One hundred and twenty
      five (74.4%) out of 168 coinfected children treated and present during the
      assessment were found stool negative for S. mansoni eggs. Out of 43 (25.6%)
      children who remained positives, 37 (22%) showed a partial reduction of eggs
      amount, and no reduction was noted in 3.6% of coinfected. The mean of haemoglobin
      concentration and the prevalence of anaemia were, respectively, 10.74+/-1.5g/dl ,
      11.2+/-1.3g/dl, and 64.8%, 51.8%, respectively, before and after treatment,
      p<0.001. Conclusion: The AS-AQ commonly used against Plasmodium allowed curing S.
      mansoni in coinfected children and increasing the Hb level. For the future, the
      randomized and multicentric clinical trials are needed for a better understanding
      of the effectiveness of AS-AQ against Schistosoma spp. The trial registration
      number was 3487183.

PMID- 30112381
TI  - The Influence of the Smile on the Perceived Facial Type Esthetics.
AB  - Objective: The objective of this study was to determine if the smile would
      influence the facial types esthetics perception for dentists, specialists, and
      laypeople. The null hypotheses for this study were that the smile has no effect
      on the perceived facial esthetics of different facial types. Materials and
      Method: A photograph of an attractive female face with an attractive smile was
      captured and manipulated using computer software, which was used to produce
      changes in the smile and facial type of the female face. Two sets of photographs
      were developed. The first set is composed of three photos showing mesofacial,
      dolichofacial, and brachyfacial faces; on these photos the smiles were masked
      intentionally. On the second set, the smile was revealed in the three face types
      (mesofacial, dolichofacial, and brachyfacial faces); this results in three
      smiling photos, where each showed a facial type with the same smile. These photos
      (6 photos in total) were rated by the participants; two hundred participants were
      recruited, 50 general dentists, 50 specialist dentists, and 100 laypeople.
      Results: The three groups (dentists, specialists, and laypeople) rated the
      mesofacial face as the highest (p value < 0.01) (64.48, 76.12, and 60.68,
      respectively), the mesofacial face was the only face that showed a significant
      difference between the three groups ratings (p value<0.01), and this significant
      difference disappeared when we compared the smiling photos for the mesofacial
      face (p value>0.01). Conclusion: Mesofacial face is considered to be the most
      attractive face in comparison to dolichofacial and brachyfacial faces. Facial
      type should not be looked at separately from the smile as the smile might
      influence the esthetics perception of the facial type.

PMID- 30112382
TI  - Volatile Oil of Amomum villosum Inhibits Nonalcoholic Fatty Liver Disease via the
      Gut-Liver Axis.
AB  - Background: The dried mature fruit of Amomum villosum has been historically used
      in China as food and in the auxiliary treatment of digestive system disorders.
      Numerous studies have shown that gastrointestinal function is closely related to
      the development of nonalcoholic fatty liver disease via the "gut-liver" axis.
      Objective: The present study aimed to explore whether the mechanism underlying
      the regulation of lipid accumulation in nonalcoholic fatty liver disease (NAFLD)
      may affect related disorders using the active ingredients in A. villosum. Design:
      Male Sprague-Dawley rats on a high-fat diet (HFD) to induce NAFLD were
      administered water extract of A. villosum (WEAV), volatile oil of A. villosum
      (VOAV), or bornyl acetate. After treatment, serum and liver total cholesterol
      (TC), triglyceride (TG), free fatty acid (FFA), aspartate aminotransferase (AST),
      alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), and
      low-density lipoprotein cholesterol (LDL-C) levels were measured. The regulatory
      role of A. villosum in the microecology of the intestines was assessed using the
      V4 region of the 16S rDNA sequencing. The expression of the intestinal tight
      junction proteins occludin and ZO-1 was also measured. The influence of A.
      villosum on TLR4-mediated chronic low-grade inflammation was evaluated based on
      the concentrations of key proteins of the TLR4/NF-kB signaling pathway. Results.
      A. villosum effectively inhibited endogenous lipid synthesis, reduced TG, TC, and
      FFA accumulation, regulated the expression of LDL-C, and decreased lipid
      accumulation in liver tissues. VOAV effectively regulated the intestinal
      microflora, improved chronic low-grade inflammation by promoting ZO-1 and
      occludin protein expressions, and inhibited the TLR4/NF-kB signaling pathway.
      Conclusion: The present study provides scientific basis for the potential
      application of A. villosum in NAFLD prevention and treatment. Additional chemical
      constituents other than bornyl acetate also contributed to the preventive effects
      of A. villosum on NAFLD.

PMID- 30112383
TI  - Relationship between TRAIL and Left Ventricular Ejection Fraction in Patients
      with ST-Elevation Myocardial Infarction Treated with Primary Percutaneous
      Coronary Intervention.
AB  - Background: Apoptosis plays an important role in the myocardial injury after
      acute myocardial infarction and in the subsequent development of heart failure.
      Aim: To clarify serum kinetics of apoptotic markers TRAIL and sFas and their
      relation to left ventricular ejection fraction (LVEF) in patients with ST
      elevation myocardial infarction (STEMI) treated with primary percutaneous
      coronary intervention (pPCI). Methods: In 101 patients with STEMI treated with
      pPCI, levels of TRAIL and sFas were measured in series of serum samples obtained
      during hospitalization and one month after STEMI. LVEF was assessed at admission
      and at one month. Major adverse cardiovascular events (MACE, i.e., death, re-MI,
      and hospitalization for heart failure and stroke) were analysed during a two-year
      followup. Results: Serum level of TRAIL significantly decreased one day after
      pPCI (50.5pg/mL) compared to admission (56.7pg/mL), subsequently increased on day
      2 after pPCI (58.8pg/mL), and reached its highest level at one month (70.3pg/mL).
      TRAIL levels on days 1 and 2 showed a significant inverse correlation with
      troponin and a significant positive correlation with LVEF at baseline. Moreover,
      TRAIL correlated significantly with LVEF one month after STEMI (day 1: r=0.402,
      p<0.001; day 2: r=0.542, p<0.001). On the contrary, sFas level was significantly
      lowest at admission (5073pg/mL), increased one day after pPCI (6370pg/mL), and
      decreased on day 2 (5548pg/mL). Significantly highest sFas level was marked at
      one month (7024pg/mL). sFas failed to correlate with LVEF at baseline or at one
      month. Both TRAIL and sFas showed no ability to predict improvement of LVEF one
      month after STEMI or a 2-year MACE (represented by 3.29%). Conclusion: In STEMI
      treated with pPCI, TRAIL reaches its lowest serum concentration after
      reperfusion. Low TRAIL level is associated with worse LVEF in the acute phase of
      STEMI as well as one month after STEMI. Higher TRAIL level appears to be
      beneficial and thus TRAIL seems to represent a protective mediator of post-AMI
      injury.

PMID- 30112384
TI  - Effects of Juniperus phoenicea Hydroalcoholic Extract on Inflammatory Mediators
      and Oxidative Stress Markers in Carrageenan-Induced Paw Oedema in Mice.
AB  - Juniperus phoenicea (J. phoenicea) is a wild tree belonging to the Cupressaceae
      family, commonly used for the treatment of several disorders. This study aimed to
      evaluate the potential protective effects of J. phoenicea hydroethanolic extract
      (EtOH-H2OE) against oxidation, acute inflammation, and pain in mice models. For
      the purpose, chemical compounds of J. phoenicea EtOH-H2OE were also analyzed by
      GC-MS. The J. phoenicea EtOH-H2OE showed a potent antioxidant activity in vitro,
      thanks to its richness in phenolic and flavonoid compounds. Mice treated with
      EtOH-H2OE (100 mg/kg BW) showed reduced paw oedema formation and decreased
      malondialdehyde (MDA) content. The evaluation of antioxidant enzyme activities in
      paw oedema tissue after five hours of carrageenan induction showed a significant
      increase (P < 0.05). Inflammatory biomarkers explorations of J. phoenicea EtOH
      H2OE-treated mice showed a restoration of the studied parameters to near-normal
      values. Furthermore, EtOH-H2OE of J. phoenicea produced a significant reduction
      of the number of abdominal writhes (P < 0.05) in a dose-dependent way.
      Phytochemical analysis of the J. phoenicea EtOH-H2OE by GC-MS showed the presence
      of hexadecanoic and stearic acids known as anti-inflammatory and analgesic
      compounds. Our investigation provided evidence that J. phoenicea EtOH-H2OE can
      effectively reduce the inflammation and pain in mice models.

PMID- 30112385
TI  - Application of Autochthonous Lactobacillus Strains as Biopreservatives to Control
      Fungal Spoilage in Caciotta Cheese.
AB  - Fungal spoilage is one of the main causes of economic losses worldwide in the
      food industry. In the last years, consumer's demands for preservative-free
      processed foods have increased as a result of growing awareness about the health
      hazards associated with chemicals. Lactic acid bacteria have been extensively
      studied for their antibacterial and antifungal potential in order to be used as
      biopreservatives. The first objective of this study was to investigate in vitro
      the antifungal activity of autochthonous Lactobacillus strains against moulds
      commonly associated with cheese spoilage. Then, the Lactobacillus strains with
      the highest inhibitory effect and broadest spectrum were tested in single or
      mixed cultures against Penicillium chrysogenum ATCC 9179 and Aspergillus flavus
      ATCC 46283 on miniature Caciotta cheese produced at laboratory scale to evaluate
      in situ their ability to prevent mould growth and to determine their impact on
      cheese organoleptic properties and starter culture activity. The growth of the
      starter lactococcal population exhibited similar trend and values during
      ripening, suggesting that the addition of lactobacilli did not influence its
      growth and survival. Inhibition of P. chrysogenum inoculated in the milk was
      determined in cheeses produced with single or mixed Lactobacillus adjuncts as
      compared to cheeses without adjunct. The mixed adjunct cultures resulted in more
      effective, significantly reducing mould counts of more than 2 log units at the
      end of ripening. The application of the adjunct cultures resulted in a delay in
      mycelial growth of P. chrysogenum and A. flavus inoculated on the cheese surface
      as well. Finally, we found no significant differences among samples for the
      sensory parameters evaluated that received similar ratings. Our results indicate
      that the selected Lactobacillus strains may have a potential effect in
      controlling mould contamination on cheeses. Further studies are currently being
      carried out to identify the molecules responsible for the antifungal activity.

PMID- 30112386
TI  - Local Injection of Allogeneic Stem Cells from Apical Papilla Enhanced Periodontal
      Tissue Regeneration in Minipig Model of Periodontitis.
AB  - Background: Discovering suitable seeding cells and simple application technique
      will be beneficial for MSC-mediated treatment of periodontitis. Stem cells from
      apical papilla (SCAPs) might be the candidate seeding cell for the periodontal
      tissues regeneration based on their origin and characters. In this research, we
      investigated the effect of SCAPs on periodontal tissue regeneration in swine by
      local injection. Methods: We established experimental periodontitis model in
      miniature pigs and then treated them with SCAPs by local injection. Clinical
      assessments, computed tomography (CT) scanning, histologic examination, and
      quantitative measurements were used to evaluate the effect of periodontal tissues
      regeneration. Results: At 12 weeks after injection, clinical assessments showed
      that probing depth, gingival recession, and attachment loss values were 5.44+/
      0.77 mm versus 7.33+/-1.0 mm (p<0.01), 2.33+/-0.33 mm versus 2.11+/-0.69 mm
      (p>0.05), and 7.78+/-0.84 mm versus 9.44+/-1.07 mm (p<0.01) in SCAPs group and
      0.9% NaCl group, respectively. CT scan results showed a significant increase of
      12.86 mm3 alveolar bone regeneration in SCAPs group compared with 0.9% NaCl
      group. In addition, histopathology results demonstrated remarkable regeneration
      in SCAPs group, whereas regeneration of periodontal tissue was hardly found in
      0.9% NaCl group. Conclusion: Local injection of SCAPs could effectively restore
      tissue defects brought about by periodontitis in the swine model. Thus, SCAPs, as
      an easily accessible dental-deriving stem cell, may serve as an alternative
      application for periodontitis treatment.

PMID- 30112387
TI  - Radial Head Resection versus Arthroplasty in Unrepairable Comminuted Fractures
      Mason Type III and Type IV: A Systematic Review.
AB  - Unrepairable comminuted fractures of the radial head Mason type III or type IV
      have poor outcomes when treated by open reduction and internal fixation. Radial
      head resection has been proposed as good option for surgical treatment, while in
      the last decades, the development of technology and design in radial head
      prosthesis has increased efficacy in prosthetic replacement. The present review
      was conducted to determine the best surgical treatment for comminuted radial head
      when ORIF is not possible. Better outcomes are reported for radial head
      arthroplasty in terms of elbow stability, range of motion, pain, and fewer
      complications compared to radial head excision. Nevertheless, radial head
      resection still can be considered an option of treatment in isolated radial head
      fractures with no associated ligament injuries lesion of ligaments or in case of
      older patients with low demanding function.

PMID- 30112388
TI  - PCG Classification Using Multidomain Features and SVM Classifier.
AB  - This paper proposes a method using multidomain features and support vector
      machine (SVM) for classifying normal and abnormal heart sound recordings. The
      database was provided by the PhysioNet/CinC Challenge 2016. A total of 515
      features are extracted from nine feature domains, i.e., time interval, frequency
      spectrum of states, state amplitude, energy, frequency spectrum of records,
      cepstrum, cyclostationarity, high-order statistics, and entropy. Correlation
      analysis is conducted to quantify the feature discrimination abilities, and the
      results show that "frequency spectrum of state", "energy", and "entropy" are top
      domains to contribute effective features. A SVM with radial basis kernel function
      was trained for signal quality estimation and classification. The SVM classifier
      is independently trained and tested by many groups of top features. It shows the
      average of sensitivity, specificity, and overall score are high up to 0.88, 0.87,
      and 0.88, respectively, when top 400 features are used. This score is competitive
      to the best previous scores. The classifier has very good performance with even
      small number of top features for training and it has stable output regardless of
      randomly selected features for training. These simulations demonstrate that the
      proposed features and SVM classifier are jointly powerful for classifying heart
      sound recordings.

PMID- 30112389
TI  - Effect of Different Head-Neck Postures on the Respiratory Function in Healthy
      Males.
AB  - Normal respiration is a very intricate function that comprises mechanical as well
      as nonmechanical components. It is shown to be affected by various factors
      including age, lifestyle, disease, and change in posture. With the increased use
      of hand held devices, everyone is prone to poor sitting postures like forward
      head posture. The purpose of this study was to evaluate the effect of assumed
      forward head posture and torticollis on the diaphragm muscle strength. A sample
      of 15 healthy males, aged 18-35 years, was recruited for this study. All subjects
      performed spirometry to measure the forced expiratory volume in 1 second (FEV1),
      the forced vital capacity (FVC), and FEV1/FVC ratio. SNIP was measured during
      upright sitting, induced forward head posture, and torticollis. Subject's mean
      age (SD) was 23(6) years. The SNIP score of the subjects during sitting with FHP
      was lower as compared to that during upright sitting. It decreased significantly
      during induced right torticollis position. This is the first study exploring the
      impact of different head and neck positions on respiratory function. Alteration
      of head and neck positions had an immediate negative impact on respiratory
      function. Clinicians should be prompted to assess respiratory function when
      assessing individuals with mal-posture.

PMID- 30112390
TI  - Advances in Emerging and Neglected Infectious Diseases 2018.

PMID- 30112391
TI  - Patterns and Determinants of Attitudes towards Genetic Risk of Cancer: Case Study
      in a Malaysian Public University.
AB  - Genetic risk to cancer is a knowledge largely confined to experts and the more
      educated sectors of the developed western countries. The perception of genetic
      susceptibility to cancer among the masses is fragmented, particularly in
      developing countries. As cancer diseases affect developing countries as much as
      developed nations, it is imperative to study perception and reception of genetic
      risk to cancer in Southeast Asia. Here, we report on a novel case study to gauge
      the awareness and attitudes towards genetic determination of cancer among the
      undergraduates of a Malaysian public university. A total of 272 university
      undergraduate students completed an online questionnaire. On causes of cancer,
      the respondents believed that cancer is caused by lifestyle and environmental
      factors, but those with science background were more likely to associate it with
      genetic factors. The results on awareness of genetic profiling of cancer risk
      showed that there are significant differences between those with science and
      nonscience background but there are no significant differences for gender and
      socioeconomic background. As for attitudes towards cancer risk, female
      respondents, those from middle socioeconomic status and science background, are
      more likely to believe in genetic determinism of cancer. The findings have
      implications on target population segmentation in strategic health communication
      on cancer.

PMID- 30112392
TI  - Abdominal Adiposity and Physical Inactivity Are Positively Associated with Breast
      Cancer: A Case-Control Study.
AB  - Objective: To examine whether breast cancer is associated with body composition
      and level of physical activity, considering the menstrual status. Methods: This
      was a case-control study with 116 women recently diagnosed with breast cancer and
      226 controls. Body composition was assessed by dual-energy X-ray absorptiometry,
      and cardiometabolic risk was assessed by conicity index and waist-to-height
      ratio. The short version of the International Physical Activity Questionnaire was
      used to estimate the level of physical activity. All analyses were adjusted for
      age and BMI. Results: The total body fat percentage, android body fat, android
      gynoid ratio, and waist circumference were positively associated (p < 0.05),
      whereas the percentage of lean body mass (p <0.05) and the level of physical
      activity (p < 0.01) were inversely associated with breast cancer in premenopausal
      women. Among postmenopausal women, physical activity decreased the chance of
      developing breast cancer by 49% (95% CI = 0.29 to 0.92, p = 0.02). Conclusion: A
      low percentage of lean body mass and high abdominal adiposity in the
      premenopausal period increase the chances of developing breast cancer. Regular
      physical activity is inversely associated with breast cancer in pre- and
      postmenopausal women.

PMID- 30112393
TI  - Combination of Genetic Markers and Age Effectively Facilitates the Identification
      of People with High Risk of Preeclampsia in the Han Chinese Population.
AB  - Objective: This study aimed to analyze the possible association between known
      genetic risks and preeclampsia in a Han Chinese population. Methods: A total of
      156 patients with preeclampsia and 286 healthy Han Chinese women were enrolled
      and genotyped for 27 genetic alleles associated with preeclampsia in different
      populations. The association between the genotypes of the individual alleles and
      preeclampsia and the possible interaction among the alleles were analyzed.
      Finally logistic models were trained with the genotypes of possible alleles
      contributing to preeclampsia. Results: Seven alleles were significantly or
      marginally significantly associated with preeclampsia, which involved six genes
      (rs4762 in AGT, rs1800896 in IL-10, rs1800629 and rs1799724 in TNFalpha,
      rs2070744 in NOS3, rs7412 in APOE, and rs2549782 in ERAP2). A multilocus
      interaction analysis further disclosed an interaction among seven alleles. A
      logistic model showing individual or synergetic contribution to preeclampsia
      could reach ~0.67 preeclampsia prediction accuracy in the Han Chinese population,
      while integration of age information could improve the performance to ~0.75
      accuracy using a fivefold training-testing evaluation strategy. Conclusions: The
      genetic factors were closely associated with preeclampsia in the Han Chinese
      population despite large ethnicity heterogeneity. The genotypes of different
      alleles also had synergetic interactions.

PMID- 30112394
TI  - Improvement of Adipose Macrophage Polarization in High Fat Diet-Induced Obese
      GHSR Knockout Mice.
AB  - Purpose: Adipose tissue inflammation is the key linking obesity to insulin
      resistance. Over 50% of the interstitial cells in adipose tissue are macrophages,
      which produce inflammatory cytokines and therefore play an important role in the
      progression of insulin resistance. Within this classification view, macrophage
      biology is driven by two polarization phenotypes, M1 (proinflammatory) and M2
      (anti-inflammatory). The unique functional receptor of ghrelin, growth hormone
      secretagogue receptor (GHSR), is a classic seven-transmembrane G protein-coupled
      receptor that is linked to multiple intracellular signaling pathways. Knockout of
      GHSR improves the obesity and glucose metabolic disorders, suggesting a crucial
      role of ghrelin activity in insulin resistance. Here, we discussed whether
      macrophage polarization phenotypes in adipose tissue were changed in GHSR
      knockout (GHSR-/-) mice. Methods: GHSR-/- mice were fed with normal chow diet
      (NCD) or high fat diet (HFD). Markers of different macrophage polarization
      phenotypes were detected by real-time RT-PCR. Results: The size of adipocytes
      decreased and interstitial cells, especially infiltrated macrophages, reduced in
      epididymal adipose tissue of GHSR-/- mice fed with HFD. Compared with wild type
      mice, the mRNA levels of inflammatory adipokines such as resistin, IL-6, and PAI
      1 were significantly lower in epididymal adipose tissue of GHSR-/- mice, whereas
      anti-inflammatory adipokine, adiponectin, was significantly higher. M1 markers,
      MCP-1, TNF-alpha, and iNOS, were significantly lower in epididymal adipose tissue
      of GHSR-/- mice, whereas M2 markers, Arg-1, Mgl-1, were Mrc1, were significantly
      higher. Conclusion: The GHSR-/- mice fed with HFD showed suppressed adipose
      inflammation, reduced macrophage infiltration, and enhanced M2 polarization of
      macrophages in adipose tissue, which improved insulin sensitivity.

PMID- 30112395
TI  - Frontal EEG Temporal and Spectral Dynamics Similarity Analysis between Propofol
      and Desflurane Induced Anesthesia Using Hilbert-Huang Transform.
AB  - Electroencephalogram (EEG) signal analysis is commonly employed to extract
      information on the brain dynamics. It mainly targets brain status and
      communication, thus providing potential to trace differences in the brain's
      activity under different anesthetics. In this article, two kinds of gamma-amino
      butyric acid (type A -GABAA) dependent anesthetic agents, propofol and desflurane
      (28 and 23 patients), were studied and compared with respect to EEG spectrogram
      dynamics. Hilbert-Huang Transform (HHT) was employed to compute the time varying
      spectrum for different anesthetic levels in comparison with Fourier based method.
      Results show that the HHT method generates consistent band power (slow and alpha)
      dominance pattern as Fourier method does, but exhibits higher concentrated power
      distribution within each frequency band than the Fourier method during both drugs
      induced unconsciousness. HHT also finds slow and theta bands peak frequency with
      better convergence by standard deviation (propofol-slow: 0.46 to 0.24; theta:
      1.42 to 0.79; desflurane-slow: 0.30 to 0.25; theta: 1.42 to 0.98) and a shift to
      relatively lower values for alpha band (propofol: 9.94 Hz to 10.33 Hz, desflurane
      8.44 Hz to 8.84 Hz) than Fourier one. For different stage comparisons, although
      HHT shows significant alpha power increases during unconsciousness stage as the
      Fourier did previously, it finds no significant high frequency (low gamma) band
      power difference in propofol whereas it does in desflurane. In addition, when
      comparing the HHT results within two groups during unconsciousness, high beta
      band power in propofol is significantly larger than that of desflurane while
      delta band power behaves oppositely. In conclusion, this study convincingly shows
      that EEG analyzed here considerably differs between the HHT and Fourier method.

PMID- 30112396
TI  - Determine the Role of FSH Receptor Binding Inhibitor in Regulating Ovarian
      Follicles Development and Expression of FSHR and ERalpha in Mice.
AB  - Mice of FRBI-1, FRBI-2, and FRBI-3 groups were intramuscularly injected with 20,
      30, and 40mg/kg, respectively, for five consecutive days. Ovarian weights of
      three FRBI groups were reduced in comparison with FSH group. Ovarian cortex
      thicknesses (OCT) of the FRBI-3 group were less than that of the FSH group
      (P<0.05). As compared to FSH group, there were fewer numbers of secondary
      follicles (SFs) and mature follicles (MF) on the ovaries of FRBI-treated mice
      numbers of primary follicles (PFs) and SFs also decreased. In FRBI-3 mice, we
      found that the primordial follicles (POF) were scarcer, the follicles developed
      poorly, and granulosa cells became apoptosis. SF numbers of FRBI-2 and FRBI-3
      groups were less than that of the FSH group on day 20 (P<0.05). Maximum
      longitudinal diameter (MLD) and transverse diameter (MTD) of three FRBI groups
      became decreased during the experiment. MLD and MTD of the FRBI-3 group were
      smaller than FSH group. Levels of FSHR mRNA and protein were less than that of CG
      and FSH group (P<0.05). ERalpha protein levels of FRBI group and serum
      concentrations of FSH and estradiol (E2) in the FRBI-treated mice were decreased
      when compared to CG and FSH group. In conclusion, FSH treatment could increase
      the numbers of SF and MF, enhance follicle development, reduce the numbers of SF
      and MF, and depress the follicular development of mice. Furthermore, FRBI
      declined the mRNA and protein levels of ERalpha and FSHR in the ovaries and
      dropped serum concentrations of FSH and E2 of mice.

PMID- 30112397
TI  - High Prevalence of Sarcopenia in HIV-Infected Individuals.
AB  - Background: Sarcopenia is a geriatric syndrome that leads to a loss of
      functionality and mortality. Methods: We assessed the prevalence of sarcopenia in
      HIV-infected patients attended in our HIV Unit who had at least two DXA scans
      from 2000 to 2016 (1,720 DXA scans from 860 individuals). Sarcopenia was
      determinate according to appendicular skeletal muscle mass index (ASM) calculated
      as the ratio between skeletal muscle mass index (SMI) by DXA and height2 (kg/m2).
      We stratified patients by gender and age (<40, 41-50, and >50 years) and
      according to the interval between DXAs (<=3, 3-7, 7-10, >10 years). The
      statistical analysis was performed using SPSS version 19. Results: Median (IQR)
      age was 52 (47; 57) years, and 76% were male. The median (IQR) time with HIV
      infection was 8 (3; 15) years. The prevalence of sarcopenia was 25.7% (95% CI,
      22.8-28.7), more prevalent in those aged >50 years (27.8%). Stratifying by
      gender, 43% of women aged >50 years presented sarcopenia compared with 8.8% of
      men. The frequency of sarcopenia increased from 37.6% to 49.4% when interval
      between DXA was 7-10 years (n=109), significantly higher in women than in men
      (p=0.016). In addition to the traditional risk factors, time with HIV infection
      was associated with sarcopenia [RR 1.780 (95% CI, 1.314-2.411), p=0.001].
      Conclusion: The prevalence and progression of sarcopenia in HIV-infected patients
      were high, mainly among women. Further studies are necessary to assess the best
      approaches to prevent this condition and its consequences.

PMID- 30112398
TI  - Digital versus Analog Procedures for the Prosthetic Restoration of Single
      Implants: A Randomized Controlled Trial with 1 Year of Follow-Up.
AB  - Aim: To compare the outcome of digital versus analog procedures for the
      restoration of single implants. Methods: Over a two-year period (2014-2016), all
      patients who had been treated in a dental center with a single implant were
      randomly assigned to receive either a monolithic zirconia crown, fabricated with
      digital workflow (test group), or a metal-ceramic crown, fabricated with analog
      workflow (control group). All patients were followed for 1 year after the
      delivery of the final crown. The outcomes were success, complications, peri
      implant marginal bone loss (PIMBL), patient satisfaction, and time and cost of
      the treatment. Results: 50 patients (22 males, 28 females; mean age 52.6+/-13.4
      years) were randomly assigned to one of the groups (25 per group). Both workflows
      showed high success (92%) and low complication rate (8%). No significant
      differences were found in the mean PIMBL between test (0.39+/-0.29mm) and control
      (0.54+/-0.32mm) groups. Patients preferred digital impressions. Taking the
      impression took half the time in the test group (20+/-5min) than in the control
      (50+/-7min) group. When calculating active working time, workflow in the test
      group was more time-efficient than in the control group, for provisional (70+/
      15min versus 340+/-37min) and final crowns (29+/-9min versus 260+/-26min). The
      digital procedure presented lower costs than the analog (?277.3 versus ?392.2).
      Conclusions: No significant clinical or radiographic differences were found
      between digital and analog procedures; however, the digital workflow was
      preferred by patients; it reduced active treatment time and costs. The present
      study is registered in the ISRCTN (http://www.isrctn.com/ISRCTN36259164) with
      number 36259164.

PMID- 30112399
TI  - Acupuncture Rescues Cognitive Impairment and Upregulates Dopamine-beta
      Hydroxylase Expression in Chronic Cerebral Hypoperfusion Rats.
AB  - Alteration of dopamine (DA) and noradrenaline (NA) contributes to cognitive
      function. Acupuncture has been shown to affect DA and NA in chronic cerebral
      hypoperfusion (CCH) rats. However, the effect of acupuncture on DA-beta
      hydroxylase (DBH), the biosynthetic enzyme of NA, remains unknown. In CCH rats we
      established chronic hypoperfusion by bilateral common carotid artery occlusion
      (two-vessel occlusion, 2VO) and treated them with acupuncture. Acupuncture
      displayed beneficial effects on hippocampus-dependent memory impairments,
      including nonspatial and spatial memory. That is also reflected in hippocampus
      long-term-potentiation (LTP). Moreover, DBH expression in the hippocampus and DBH
      activity in cerebrospinal fluid were upregulated after acupuncture treatment. In
      conclusion, these in vivo findings suggest that acupuncture exerts a therapeutic
      effect on hippocampus-dependent memory and hippocampus LTP in CCH rats, which may
      be partially related to the modulation of DBH in the hippocampus.

PMID- 30112400
TI  - Reduced beta2GPI Inhibiting Glomerular Mesangial Cells VEGF-NO Axis Uncoupling
      Induced by High Glucose.
AB  - VEGF-NO axis uncoupling is an important pathogenesis for DN. Reduced beta2GPI
      could play a part in VEGF signaling pathway and has a protective effect on
      diabetic vascular disease. This study investigates the effect of reduced beta2GPI
      on glomerular mesangial cells VEGF-NO axis uncoupling induced by high glucose.
      Compared to control group, glomerular mesangial cell line HBZY-1 cells treated
      with high glucose expressed higher levels of VEGF mRNA and protein and produced
      more ROS but less NO. The related proteins related to VEGF-NO axis were assayed.
      High glucose could significantly increase the expression of the level of VEGFR2
      and obviously increase phosphorylation of Akt and eNOS but significantly decrease
      the expression of GTP cyclohydrolase 1 (GCH-1), reducing the production of eNOS
      dimer. Both beta2GPI and reduced beta2GPI partly reverse these effects caused by
      high glucose. Reduced beta2GPI had stronger effect than beta2GPI. GCH-1 is the
      speed limit of tetrahydrobiopterin (BH4) synthesis enzyme. As the key part of
      eNOS cofactors, BH4 could partly restore eNOS dimer induced by high glucose. Our
      results indicated that high glucose could interfere with eNOS dimer formation.
      beta2GPI and reduced beta2GPI can partly reverse the VEGF-NO axis uncoupling by
      restoring the GCH-1 expression level and then promote eNOS dimer formation.

PMID- 30112401
TI  - Nonalcoholic Fatty Liver Disease Is Associated with Increased Atrial Fibrillation
      Risk in an Elderly Chinese Population: A Cross-Sectional Study.
AB  - Background: Atrial fibrillation and nonalcoholic fatty liver disease are two
      pathological conditions that are highly prevalent worldwide and share multiple
      CVD risk factors. There are rare researches performed among elderly adults. Aims:
      We conducted this cross-sectional analysis of elderly adults (>=65 years) to
      investigate the association between atrial fibrillation and nonalcoholic fatty
      liver disease. Methods: We analyzed clinical data of the elderly adults (>= 65
      years) who had health examination in Zhenhai Lianhua Hospital, Ningbo, China, in
      2014. Results: 522 of the 1688 participants were diagnosed with nonalcoholic
      fatty liver disease, and 39 participants were diagnosed as having atrial
      fibrillation. Nonalcoholic fatty liver disease was associated with risk factors
      for AF in the elderly Chinese population (OR 1.95, 95% CI 1.03-3.69). Adjustments
      for age, gender, systolic blood pressure, fasting plasma glucose, gamma-glutamyl
      transpeptidase, high-density lipoprotein, triglycerides, total cholesterol and
      albumin, nonalcoholic fatty liver disease, and prevalent atrial fibrillation
      remained statistically significant (OR 2.76, 95% CI 1.32-5.77). Conclusions: Our
      results show that nonalcoholic fatty liver disease is associated with an
      increased risk of atrial fibrillation in an elderly Chinese population.

PMID- 30112402
TI  - Treatment Algorithm of Peripancreatic Arteries Aneurysm Coexisting with Coeliac
      Artery Lesion: Single Institution Experience.
AB  - Introduction: True aneurysms of peripancreatic arterial arcades (PAAAs)
      coexisting with celiac axis lesion are often asymptomatic. However, they may
      rupture regardless of their size and cause life-threatening hypovolemia. No
      treatment guidelines exist to date. We present a series of 21 patients and our
      management algorithm. Material and Methods: For ruptured aneurysms we preformed
      endovascular embolization. Further treatment was dependent on patient's condition
      and control studies. In case of unruptured aneurysms, we assessed collateral
      circulation between superior mesenteric artery and celiac axis in angio-CT. If
      there was a pathway free from aneurysms, endovascular approach was chosen.
      Otherwise, surgical or combined treatment was favored. Results: Endovascular
      treatment was performed in 14 patients with no complications. Follow-up studies
      revealed incomplete occlusion of the aneurysms in two cases. Surgical or combined
      treatment was performed in 7 patients with three serious perioperative
      complications. They were managed conservatively in two cases and surgically in
      one. Follow-up studies showed aneurismal dilatation and stenosis of a renohepatic
      by-pass in one case. Conclusion: We present our management algorithm of PAAAs.
      Our results support the leading role of endovascular treatment. We present its
      limitations favoring surgical or combined treatment. All patients should be
      carefully followed.

PMID- 30112403
TI  - A Meta-Analysis of the Influencing Factors for Tracheostomy after Cervical Spinal
      Cord Injury.
AB  - Background: Traumatic cervical spinal cord injury (CSCI) is a common disease that
      has high complication, disability, and mortality rates and a poor prognosis.
      Tracheostomy is an important supportive therapy for patients with CSCI. However,
      a consensus on the predictive factors for tracheostomy after CSCI has not been
      reached. Objective: This meta-analysis study assessed the influencing factors for
      tracheostomy after CSCI. Methods: We searched for relevant studies on the
      influencing factors for tracheostomy after CSCI. The extracted data were analyzed
      using RevMan 5.3 software. We calculated the odds ratio (OR) or mean difference
      (MD) and 95% confidence intervals (CIs). Results: Sixteen eligible studies
      containing 9697 patients with CSCI were selected. The pooled OR (MD) and 95% CI
      of the influencing factors were as follows: age (mean +/- SD): -0.98 (-4.00 to
      2.03), advanced age: 1.93 (0.80 to 4.63), sex (male): 1.29 (1.12 to 1.49),
      American Spinal Injury Association Impairment Scale (AIS) A grade: 7.79 (5.28 to
      11.50), AIS B grade: 1.15 (1.13 to 2.02), AIS C grade: 0.28 (0.20 to 0.41), AIS D
      grade: 0.04 (0.02 to 0.09), neurological level of injury (upper CSCI): 2.36 (1.51
      to 3.68), injury severity score (ISS): 8.97 (8.11 to 9.82), Glasgow Coma Scale
      (GCS) score <=8: 6.03 (2.19 to 16.61), thoracic injury: 1.78 (1.55 to 2.04),
      brain injury: 0.96 (0.55 to 1.69), respiratory complications: 5.97 (4.03 to
      8.86), smoking history: 1.45 (0.99 to 2.13), traffic accident injury: 1.27 (0.92
      to 1.74), and fall injury: 0.72 (0.52 to 1.01). Conclusions: The current evidence
      shows that male sex, AIS A grade, AIS B grade, neurological level of injury
      (upper CSCI), high ISS, GCS<=8, thoracic injury, and respiratory complications
      are risk factors for tracheostomy after CSCI, and AIS C grade and AIS D grade are
      protective factors. This study will allow us to use these factors for
      tracheostomy decisions and ultimately optimize airway management in patients with
      CSCI.

PMID- 30112404
TI  - Failure Predictor Factors of Conservative Treatment in Pediatric Forearm
      Fractures.
AB  - The aim of this study is to evaluate the predictive efficacy of the radiographic
      parameters and the relationship between the radiographic results and the clinical
      data. We carried out a retrospective study analyzing the data of 225 pediatric
      patients with forearm fractures treated conservatively. Two orthopaedists
      examined 4 different radiographic parameters. They compared CI and radial
      translation parameters at T0, in terms of indication of type of treatment and
      predictive efficacy. Afterwards, the two orthopaedists analyzed X-rays performed
      at T1, evaluating radiographic results according to radial shortening and angle
      parameters. From the analysis of the CI measured by Observer 1, 135 patients out
      of 225 had retrospective indication to conservative treatment; the frequency of
      failure was 18/135 (13.3%). Observer 2 indicated conservative treatment in 144
      patients out of 225 and the proportion of failure was 21/144 (14.6%). As regards
      the radial translation, Observer 1 reported a frequency of failure of 78/225
      (34.7%) and Observer 2 reported 75/222 (33.8%). Furthermore the authors detected
      a deficit of pronosupination for the patients considered to have failure
      according to radiographic results. The authors defined the greater reliability of
      CI with respect to the radial translation parameter and the direct relationship
      between radiographic failure and clinical-functional data.

PMID- 30112406
TI  - Knowledge Level, Attitude, and Behaviors of Farmers in Cukurova Region regarding
      the Use of Pesticides.
AB  - Introduction and Purpose: Farmers are particularly at high risk of pesticide
      exposure due to added risk from occupational exposure. The aim of this study is
      to evaluate knowledge level of farmers in the Cukurova region of the effects of
      pesticides, toxic symptoms, and protective equipment as well as assessing their
      attitudes and practices regarding pesticides. Material and Method: A total of 420
      seasonal agricultural workers in Karatas District of Adana Province, Turkey, were
      included in the study. The questionnaire form consisting of 3 sections was
      administered using face-to-face interview method. Results: The mean age of the
      participants was 40.2 +/- 10.6 years. They were engaged in farming for a mean
      duration of 18.5 +/- 10.6 years. All of them used pesticides, but none of them
      had been trained on the use of pesticides. Only 26.2% of them stored pesticides
      in a private depot. The farmers who took empty pesticide containers to special
      collection bins or centers constituted only 4.3% of them. While 84.0% of them
      thought that pesticides could have a negative impact on human health, 5.0% of
      them had experienced a medical problem and 1.0% of them were poisoned after
      applying pesticides. Conclusion: The results show that knowledge level of farmers
      of safe use of pesticides is very inadequate. This lack of knowledge adversely
      affects workers' quality of life as well as occupational health and safety.
      Appropriate training programs should be organized to increase their level of
      knowledge.

PMID- 30112405
TI  - Ag-Introduced Antibacterial Ability and Corrosion Resistance for Bio-Mg Alloys.
AB  - Bone implants are expected to possess antibacterial ability and favorable
      biodegradability. Ag possesses broad-spectrum antibacterial effects through
      destroying the respiration and substance transport of bacteria. In this study, Ag
      was introduced into Mg-3Zn-0.5Zr (ZK30) via selective laser melting technology.
      Results showed that ZK30-Ag exhibited a strong and stable antibacterial activity
      against the bacterium Escherichia coli. Moreover, the degradation resistance was
      enhanced due to the comprehensive effect of positive shifted corrosion potential
      (from -1.64 to -1.53 V) and grains refinement. The positive shifted corrosion
      potential reduced the severe galvanic corrosion by lowering the corrosion
      potential difference between the matrix and the second phase. Meanwhile, the
      introduction of Ag caused the grain refinement strengthening and precipitated
      phase strengthening, resulting in improved compressive yield strength and
      hardness. Furthermore, ZK30-0.5Ag exhibited good biocompatibility. It was
      suggested that Ag-modified ZK30 was potential candidate for bone implants.

PMID- 30112407
TI  - Aphrodisiac Activity of Eulophia macrobulbon Extract on Erectile Dysfunction in
      Male Aged Rats.
AB  - This study investigated the effect of Eulophia macrobulbon (EM) extract on sexual
      performance in aged-related erectile dysfunction (ED) rats. The ethanol EM
      extract at the doses of 15, 150, and 450 and sildenafil citrate at the dose of 5
      mg/kg body weight (BW) were administered orally to the aged male rats once daily
      for 21 days. Mating parameters and intracavernosal pressure (ICP) were measured
      to evaluate their sexual and erection functions. Numbers of sperm and sperm
      motility as well as the diameter of seminiferous tubules were observed. The serum
      testosterone and 3',5'-cyclic guanosine monophosphate (cGMP) concentration in the
      rat penile tissue were analyzed. The results showed the significant increased
      sexual motivation, copulatory performance, and ICP of aged rats treated with
      sildenafil citrate and all doses of EM extract as compared to control aged rats.
      Moreover, their serum testosterone levels were slightly increased and significant
      increase in penile cGMP concentration was observed in these aged rats treated
      with sildenafil citrate and EM extract. The results suggest that treatment with
      EM could inhibit activity of PDE5 in penile tissue resulting in the increased
      cGMP level and bring to the improvement of erectile function and sexual
      performance.

PMID- 30112408
TI  - Do Culture-Negative Periprosthetic Joint Infections Have a Worse Outcome Than
      Culture-Positive Periprosthetic Joint Infections? A Systematic Review and Meta
      Analysis.
AB  - Background: Culture-negative periprosthetic joint infections (CN PJI) have not
      been well studied, and due to the lack of consensus on PJI, especially with
      culture-negative infections, there are considerable uncertainties. Due to the
      challenging clinical issue of CN PJI the aim of this systematic review is to
      describe incidence, diagnosis, and treatment outcomes based on the current
      literature on CN PJI. Hypothesis: The review is designed to assess the formal
      hypothesis that CN PJI of the hip and knee have a poorer outcome when compared
      with culture-positive ones. Study Design: It is systematic review with level of
      evidence 3. Methods: EMBASE, MEDLINE, and the Cochrane Library were searched
      electronically in January 2018. All studies regarding CN PJI of the hip or knee
      published in English or German with a minimum of 10 patients were included.
      Afterwards, the authors performed a descriptive analysis of diagnosis and
      treatment outcome. Result: Eight studies were identified that met the inclusion
      criteria. The incidence of CN PJI in the hip or knee ranged from 7% to 42 %. The
      included studies were pooled to give an overall incidence rate estimate of 11 %
      [95% confidence interval (CI): 10-12] based on a random-effects model. The most
      common surgical intervention was the two-stage revision of prosthesis with 283
      patients. Postoperatively, the majority of patients received vancomycin as the
      antibiotic treatment, alone or in combination with other antibiotics. The rate of
      succesfully treated infections varied from 85% to 95 % in all included studies.
      The two-stage exchange arthroplasty had the best outcome, based on the infection
      free survival rate of 95%, five years after treatment. Conclusions: We conclude
      that CN PJI have the same or even better results than culture-positive
      infections. Nonetheless, a standardized diagnostic protocol and evidence-based
      treatment strategies for CN PJI should be implemented for further studies.

PMID- 30112409
TI  - Risks in Surrogacy Considering the Embryo: From the Preimplantation to the
      Gestational and Neonatal Period.
AB  - Surrogacy is an assisted reproduction-based approach in which the intended
      parents assign the gestation and birth to another woman called the surrogate
      mother. The drivers of surrogacy refer largely to infertility, medical
      conditions, same-sex couples' parenting, and cases of diversity regarding sexual
      identity and orientation. Surrogacy consists of a valid option for a variety of
      conditions or circumstances ranging from medical to social reasons. However,
      surrogacy may be associated with risks during the preimplantation, prenatal, and
      neonatal period. It became obvious during the exhaustive literature research that
      data on surrogacy and its association with factors specific to the IVF practice
      and the options available were not fully represented. Could it be that surrogacy
      management adds another level of complexity to the process from the ovarian
      stimulation, the subsequent IVF cycle, and the techniques employed within the IVF
      and the Genetic Laboratory to the fetal, perinatal, and neonatal period? This
      work emphasizes the risks associated with surrogacy with respect to the
      preimplantation embryo, the fetus, and the infant. Moreover, it further calls for
      larger studies reporting on surrogacy and comparing the surrogate management to
      that of the routine IVF patient in order to avoid suboptimal management of a
      surrogate cycle. This is of particular importance in light of the fact that the
      surrogate cycle may include not only the surrogate but also the egg donor, sperm
      donor, and the commissioning couple or single person.

PMID- 30112410
TI  - Cerebral Ischemic Postconditioning Plays a Neuroprotective Role through
      Regulation of Central and Peripheral Glutamate.
AB  - Following cerebral ischemia/reperfusion (I/R) injury, a series of
      pathophysiological processes are stimulated in both the central nervous system
      (CNS) and the periphery, including, but not limited to, the peripheral immune and
      endocrine systems and underregulation of the neuroendocrine-immune network.
      Glutamate (Glu) is an important excitatory neurotransmitter in the CNS; its
      excitotoxicity following cerebral ischemia has been a focus of study for several
      decades. In addition, as a novel immunoregulator, Glu also regulates immune
      activity in both the CNS and periphery and may connect the CNS and periphery
      through regulation of the neuroendocrine-immune network. Ischemic
      postconditioning (IPostC) is powerful and activates various endogenous
      neuroprotective mechanisms following cerebral I/R, but only a few studies have
      focused on the mechanisms associated with Glu to date. Given that Glu plays an
      important and complex pathophysiological role, the understanding of Glu-related
      mechanisms of IPostC is an interesting area of research, which we review here.

PMID- 30112411
TI  - Association between Y-Maze Acquisition Learning and Major Histocompatibility
      Complex Class II Polymorphisms in Mice.
AB  - Objective: To explore the association between the acquisition process in the Y
      maze and H-2 class II polymorphisms in mice. Methods: Mice were trained for 5
      consecutive days in the Y-maze. The value of the slope of the latent period was
      considered an indication for the acquisition process. A slope < 0 indicated
      learning during the training and a slope > 0 indicated no learning. The H-2
      polymorphism was determined with PCR amplification, and the correlation between
      the alleles and the acquisition process was analyzed. Results: The overall
      percentage of mice that learned was 46.1%. The percentage of mice that had
      learned with MudoEb5 (37.9%) was significantly lower than that of mice without
      MudoEb5 (61.1%; P < 0.05). The percentage of mice that had learned with MudoEb7
      (26.1%) was significantly lower than that of mice without MudoEb7 (51.9%; P <
      0.05). Conclusions: The major histocompatibility complex (MHC) and other alleles
      may be involved in the acquisition process. There may be a biological basis for
      learning in mice.

PMID- 30112412
TI  - The Use of a Novel Porcine Derived Acellular Dermal Matrix (Mucoderm) in Peri
      Implant Soft Tissue Augmentation: Preliminary Results of a Prospective Pilot
      Cohort Study.
AB  - Objective: Over the years, several techniques have been proposed for soft tissue
      augmentation around dental implants in order to improve keratinized mucosa width
      (KMW). Recently, a porcine derived acellular dermal matrix (Mucoderm(r)) has been
      proposed as autogenous graft substitute in order to avoid palatal harvesting and
      obtain comparable results to connective tissue grafts, in terms of aesthetics and
      function. The aim of this study is to present the one-year follow-up results of
      this matrix in peri-implant soft tissue augmentation procedures. Material and
      Methods: Twelve patients were enrolled in this pilot prospective study: a dental
      implant was placed in the upper premolar area and, at implant uncovering after
      eight weeks, the matrix was inserted. KMW gain was considered as primary outcome
      variable. Results: After one month from matrix insertion, mean KMW was 7.86+/
      3.22 mm (100%), with no statistically significant intragroup variations (p>0.05).
      No membrane exposures or wound healing complications occurred during
      postoperative phase and, after one year, mean KMW was 5.67+/-2.12 mm (72.13%).
      Conclusions: The results of the present pilot study indicate that by placing a
      Mucoderm membrane during implant surgery the keratinized tissue width can be
      augmented, and the width remains stable for the assessment period of 12 months.
      Further studies with greater power and longer investigation period are needed to
      confirm the suggestion for clinical use. Clinical trial registration number is
      EudraCT number 2018-000147-16.

PMID- 30112413
TI  - Fertility Preservation: Current and Future Perspectives for Oncologic Patients at
      Risk for Iatrogenic Premature Ovarian Insufficiency.
AB  - Progress in recent years in the efficacy of oncologic treatment and early
      diagnosis of cancer has determined an increase in life expectance in cancer
      patients. About 10% of all cancer cases affect women younger than 45 years;
      therefore nowadays approximately 5-6% of the population in childbearing age
      consists in cancer survivors. A crucial issue is the high risk of premature
      ovarian insufficiency due to possible gonadotoxic effects of oncologic
      treatments. Considering combined chemotherapy, radiation therapy, and bone marrow
      transplantation, this risk can reach 92-100%, depending on the age and ovarian
      reserve of the patient, as well as the schedule and type of therapy.
      International guidelines recommend addressing all the patients diagnosed with a
      neoplasia treatable with potentially gonadotoxic therapies to fertility
      preservation. Moreover, fertility preservation also seems to reserve fascinating
      implications for women who want to delay childbearing for social reasons or women
      affected with endometriosis, who could receive unexpected opportunities. At
      present, the most widespread techniques to preserve fertility in adult women are
      embryo or oocyte cryopreservation, depending on the presence of a partner or
      according to legislative issues, but these procedures require time for ovarian
      stimulation. In prepubertal patients or when there is no possibility of delaying
      chemotherapy, ovarian tissue cryopreservation and subsequent transplantation
      represent the main strategy.

PMID- 30112414
TI  - Role of White Blood Cells in Blood- and Bone Marrow-Based Autologous Therapies.
AB  - There has been significant debate over the role of white blood cells (WBCs) in
      autologous therapies, with several groups suggesting that WBCs are purely
      inflammatory. Misconceptions in the practice of biologic orthopedics result in
      the simplified principle that platelets deliver growth factors, WBCs cause
      inflammation, and the singular value of bone marrow is the stem cells. The aim of
      this review is to address these common misconceptions which will enable better
      development of future orthopedic medical devices. WBC behavior is adaptive in
      nature and, depending on their environment, WBCs can hinder or induce healing.
      Successful tissue repair occurs when platelets arrive at a wound site,
      degranulate, and release growth factors and cytokines which, in turn, recruit
      WBCs to the damaged tissue. Therefore, a key role of even pure platelet-rich
      plasma is to recruit WBCs to a wound. Bone marrow contains a complex mixture of
      vascular cells, white blood cells present at much greater concentrations than in
      blood, and a small number of progenitor cells and stem cells. The negative
      results observed for WBC-containing autologous therapies in vitro have not
      translated to human clinical studies. With an enhanced understanding of the
      complex WBC biology, the next generation of biologics will be more specific,
      likely resulting in improved effectiveness.

PMID- 30112415
TI  - Isocentric Navigation for the Training of Percutaneous Endoscopic Transforaminal
      Discectomy: A Feasibility Study.
AB  - Background: Percutaneous endoscopic transforaminal discectomy (PETD) is usually
      chosen for lumbar disc herniation due to its obvious advantages such as small
      incision and absence of nerve or muscular traction. However, learning PETD is a
      great challenge for inexperienced surgeons. Objective: The study aimed to
      investigate whether isocentric navigation would be beneficial in PETD training.
      Methods: A total of 117 inexperienced surgeons were trained with PETD at L2/3,
      L3/4, L4/5, and L5/S1 on the cadavers without (Group A n=58) or with (Group B
      n=59) isocentric navigation. Puncture times, fluoroscopy times, exposure time,
      and radiation dose were recorded and analyzed. Questionnaires were conducted
      before and after the training program. Result: Isocentric navigation could
      improve young surgeons' satisfaction with the training program and decrease the
      puncture times, fluoroscopy times, exposure time, and radiation dose
      significantly (P<0.001). Conclusion: Isocentric navigation contributes to the
      training of PETD and may improve its standardization, homogenization, and
      generalization.

PMID- 30112416
TI  - Gender Perspective on Older People's Exercise Preferences and Motivators in the
      Context of Falls Prevention: A Qualitative Study.
AB  - Background: Several factors have previously been identified to positively
      influence the uptake and adherence for fall prevention exercise programmes. There
      is, however, a lack of studies investigating if men and women differ in their
      views and preferences for fall prevention exercises. Aim: To explore exercise
      preferences and motivators of older community-dwelling women and men in the
      context of falls prevention from a gender perspective. Methods: Workshops
      including multistage focus group discussions were conducted with 18 older
      community-dwelling people with and without history of falls. Participants were
      purposively selected and divided into two groups. Each group met on six occasions
      over a period of five months. Participatory and Appreciative Action and
      Reflection methodology was used to guide the discussions. A qualitative content
      analysis approach was used in the analysis. Results: Older participants had many
      diverse preferences and confirmed that individually tailored exercise, in terms
      of mode, intensity, challenge, and social context, is important. Moreover,
      important factors for exercise adherence and maintenance included the experience
      of individual confirmation; different spirit lifters to increase enjoyment; and
      personal tricks to maintain exercise routines. The individual differences within
      genders were more diverse than the differences between women and men. Conclusion:
      Exercise interventions to prevent falls should be individually tailored, based on
      the specific needs and preferences of the older participant, and do not appear to
      require gender specific approaches. To increase adherence, intrinsic motivation
      for exercise may be encouraged by competence enhancing confirmations, energizing
      spirit lifters, and practical tips for exercise maintenance. The study provides
      an awareness about women's and men's preferences for fall prevention exercises,
      and this information could be used as guidance in designing inclusive exercise
      interventions.

PMID- 30112418
TI  - A Long-Term Study of a Lipid-Buprenorphine Implant in Rats.
AB  - Animal models to study opiates are of growing interest. We have examined the
      short-term safety of buprenorphine implants in Fischer F344/NTac rats treated
      with excess doses of a cholesterol-triglyceride suspension of buprenorphine. A
      single injection of 0.65 mg/kg afforded clinically significant blood levels of
      analgesia for 3 days. Chemistry, hematology, coagulation, and urinalysis values
      with 2- to 10-fold excess doses of the drug-lipid suspension were within normal
      limits. Histopathology findings were unremarkable. The skin and underlying tissue
      surrounding the drug injection were unremarkable. Here we report the results of a
      long-term follow-up study of female rats injected with 0.65 and 1.3 mg/kg. The 14
      month evaluation showed no abnormal findings that could be attributed to the drug
      or lipid suspension. These results confirm the safety of cholesterol-triglyceride
      carrier systems for subcutaneous drug delivery in laboratory animals and suggest
      that this model may be used to study long-term effects of opiate therapy.

PMID- 30112417
TI  - iTRAQ-Based Proteomics Analysis Reveals the Effect of Rhubarb in Rats with
      Ischemic Stroke.
AB  - Background. Rhubarb, a traditional Chinese medicine, promotes viscera and remove
      blood stasis. Rhubarb is skilled in smoothening meridians, improving blood
      circulation which exhibits better efficacy on cerebral ischemic stroke. In this
      study, we aimed to analyze the underlying mechanisms of rhubarb which treated
      rats of middle cerebral artery occlusion (MCAO) model according to an iTRAQ-based
      proteomics and bioinformatics analysis. 30 rats were randomly allocated into
      three groups including sham group (SG), model group (MG), and rhubarb group (RG).
      Rhubarb group was given a gavage of rhubarb decoction at dose of 3 g/kg and the
      remaining groups were prepared with normal saline by gavage. Rats from MG and RG
      were induced into MCAO model. The effects of rhubarb were estimated by Modified
      Neurological Severity Score (mNSS) and cerebral infarct volume. The brain tissues
      were measured via the quantitative proteomic approach of iTRAQ coupled to liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Furthermore, the
      bioinformatics analysis of overlapping differentially expression proteins (DEPs)
      was conducted by DAVID, KEGG, and Cytoscape. Specific selective DEPs were
      validated by Western blotting. Rats treated with rhubarb after MCAO showed a
      significant reduction on mNSS and cerebral infarct volume compared with MG. In MG
      versus SG and RG versus MG, we identified a total of 4578 proteins, of which 287
      were DEPs. There were 76 overlapping DEPs between MG versus SG and RG versus MG.
      Through bioinformatics analysis, 14 associated pathways were searched including
      cGMP-PKG signaling pathway, tuberculosis, synaptic vesicle cycle, amyotrophic
      lateral sclerosis, long-term potentiation, and so on. 76 overlapping DEPs mainly
      involved synaptic vesicle cycling biological processes based on GO annotation.
      Further, the selective overlapping DEPs were verified at the protein level by
      using Western blotting. Our present study reveals that rhubarb highlights
      promising neuroprotective effect. Rhubarb exerts novel therapeutic action via
      modulating multiple proteins, targets, and pathways.

PMID- 30112419
TI  - Accurate Titration of Infectious AAV Particles Requires Measurement of
      Biologically Active Vector Genomes and Suitable Controls.
AB  - Although the clinical use of recombinant adeno-associated virus (rAAV) vectors is
      constantly increasing, the development of suitable quality control methods is
      still needed for accurate vector characterization. Among the quality criteria,
      the titration of infectious particles is critical to determine vector efficacy.
      Different methods have been developed for the measurement of rAAV infectivity in
      vitro, based on detection of vector genome replication in trans-complementing
      cells infected with adenovirus, detection of transgene expression in permissive
      cells, or simply detection of intracellular vector genomes following the
      infection of indicator cells. In the present study, we have compared these
      methods for the titration of infectious rAAV8 vector particles, and, to assess
      their ability to discriminate infectious and non-infectious rAAV serotype 8
      particles, we have generated a VP1-defective AAV8-GFP vector. Since VP1 is
      required to enter the cell nucleus, the lack of VP1 should drastically reduce the
      infectivity of rAAV particles. The AAV8 reference standard material was used as a
      positive control. Our results demonstrated that methods based on measurement of
      rAAV biological activity (i.e., vector genome replication or transgene
      expression) were able to accurately discriminate infectious versus non-infectious
      particles, whereas methods simply measuring intracellular vector genomes were
      not. Several cell fractionation protocols were tested in an attempt to
      specifically measure vector genomes that had reached the nucleus, but genomes
      from wild-type and VP1-defective AAV8 particles were equally detected in the
      nuclear fraction by qPCR. These data highlight the importance of using suitable
      controls, including a negative control, for the development of biological assays
      such as infectious unit titration.

PMID- 30112420
TI  - Determining the Minimally Effective Dose of a Clinical Candidate AAV Vector in a
      Mouse Model of Crigler-Najjar Syndrome.
AB  - Liver metabolism disorders are attractive targets for gene therapy, because low
      vector doses can reverse the buildup of toxic metabolites in the blood. Crigler
      Najjar syndrome is an inherited disorder of bilirubin metabolism that is caused
      by the absence of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)
      activity. This syndrome is characterized by hyperbilirubinemia and jaundice.
      Unfortunately, current phototherapy treatment is not effective long term. We
      intravenously injected phototherapy-rescued adult UGT1 knockout mice with 2.5 *
      1010-2.5 * 1013 genome copies (GC)/kg of a clinical candidate vector,
      AAV8.TBG.hUGT1A1co, to study the treatment of disease compared to vehicle-only
      control mice. There were no apparent vector-related laboratory or clinical
      sequelae; the only abnormalities in clinical pathology were elevations in liver
      transaminases, primarily in male mice at the highest vector dose. Minimal to mild
      histopathological findings were present in control and vector-administered male
      mice. At vector doses greater than 2.5 * 1011 GC/kg, we observed a reversal of
      total bilirubin levels to wild-type levels. Based on a significant reduction in
      serum total bilirubin levels, we determined the minimally effective dose in this
      mouse model of Crigler-Najjar syndrome to be 2.5 * 1011 GC/kg.

PMID- 30112422
TI  - Time-Frequency Masking in the Complex Domain for Speech Dereverberation and
      Denoising.
AB  - In real-world situations, speech is masked by both background noise and
      reverberation, which negatively affect perceptual quality and intelligibility. In
      this paper, we address monaural speech separation in reverberant and noisy
      environments. We perform dereverberation and denoising using supervised learning
      with a deep neural network. Specifically, we enhance the magnitude and phase by
      performing separation with an estimate of the complex ideal ratio mask. We define
      the complex ideal ratio mask so that direct speech results after the mask is
      applied to reverberant and noisy speech. Our approach is evaluated using
      simulated and real room impulse responses, and with background noises. The
      proposed approach improves objective speech quality and intelligibility
      significantly. Evaluations and comparisons show that it outperforms related
      methods in many reverberant and noisy environments.

PMID- 30112421
TI  - Use of Precision-Cut Lung Slices as an Ex Vivo Tool for Evaluating Viruses and
      Viral Vectors for Gene and Oncolytic Therapy.
AB  - Organotypic slice cultures recapitulate many features of an intact organ,
      including cellular architecture, microenvironment, and polarity, making them an
      ideal tool for the ex vivo study of viruses and viral vectors. Here, we describe
      a procedure for generating precision-cut ovine and murine tissue slices from
      agarose-perfused normal and murine melanoma tumor-bearing lungs. Furthermore, we
      demonstrate that these precision-cut lung slices can be maintained up to 1 month
      and can be used for a range of applications, which include characterizing the
      tissue tropism of viruses that cannot be propagated in cell monolayers,
      evaluating the transducing properties of gene therapy vectors, and, finally,
      investigating the tumor specificity of oncolytic viruses. Our results suggest
      that ex vivo lung slices are an ideal platform for studying the tissue
      specificity and cancer cell selectivity of gene therapy vectors and oncolytic
      viruses prior to in vivo studies, providing justification for pre-clinical work.

PMID- 30112423
TI  - Respiratory Syncytial Virus Infection in Mice and Detection of Viral Genomes in
      the Lung Using RT-qPCR.
AB  - Respiratory syncytial virus (RSV) is a single-stranded negative sense RNA virus
      that belongs to the paramyxovirus family. RSV infections lead to a variety of
      clinical outcomes ranging from a mild "cold-like disease" to death. Infection is
      usually more severe in infants and the elderly. RSV is associated with the
      development and exacerbation of chronic lung conditions including asthma, and it
      is a major cause of hospitalizations in infants. Because of its clinical
      relevance, experimental animal models to study RSV in vivo are needed. The most
      common and accessible animal model in research laboratories is the mouse.
      However, commonly use RSV strains poorly establish infection in mice and thus
      titration of the virus from mouse lungs to confirm infection is not sensitive
      enough to detect early viral infection. Here we discuss in detail how to infect
      BALB/c mice with RSV and how to detect RSV genomes in the lung using reverse
      transcription quantitative PCR (RT-qPCR). This method allows detection of viral
      genomes as early as day 1 post-infection (shown in Figure 2), whereas traditional
      TCID50 fails to detect significant virus until after day 2 post-infection. Of
      note, despite of higher sensitivity, genome RT-qPCR only shows the production of
      viral genomes and thus positive results for this assay are not proof of
      production of infectious viral particles.

PMID- 30112424
TI  - Fluorescent Labeling of Rat-tail Collagen for 3D Fluorescence Imaging.
AB  - Rat tail collagen solutions have been used as polymerizable in vitro three
      dimensional (3D) extracellular matrix (ECM) gels for single and collective cell
      migration assays as well as spheroid formation. These 3D hydrogels are a
      relatively inexpensive, simple to use model system that can mimic the in vivo
      physical characteristics of numerous tissues within the body, namely the skin.
      While confocal imaging techniques such as fluorescence reflection and two-photon
      microscopy are able to visualize collagen fibrils during 3D imaging without
      fluorescence, other imaging modalities require direct conjugation of fluorescent
      dyes to collagen. Here we detail how to generate 3D collagen gels labeled with a
      fluorescent dye. Furthermore, we go through the steps required to reproducibly
      generate bright collagen hydrogels that are suitable for live cell 3D imaging
      techniques.

PMID- 30112425
TI  - Measurement of TLR4 and CD14 Receptor Endocytosis Using Flow Cytometry.
AB  - After recognizing extracellular bacterial lipopolysaccharide (LPS), the toll-like
      receptor 4 (TLR4)-CD14 signaling complex initiates two distinct signaling
      pathways-one from the plasma membrane and the other from the signaling endosomes
      (Kagan et al., 2008). Understanding the early stages of TLR4 signal transduction
      therefore requires a robust and quantitative method to measure LPS-triggered TLR4
      and CD14 receptor endocytosis, one of the earliest events of LPS detection. Here,
      we describe a flow cytometry-based method that we used recently to study the role
      of the ion channel TRPM7 in TLR4 endocytosis (Schappe et al., 2018). The assay
      relies on stimulating the cells with LPS and measuring the cell surface levels of
      TLR4 (or CD14) at various time points using flow cytometry. Although we detail
      the method specifically for TLR4 and CD14 from murine bone marrow-derived
      macrophages, it can be readily adapted to evaluate receptor endocytosis in a
      variety of other signaling contexts.

PMID- 30112426
TI  - Measuring CD38 Hydrolase and Cyclase Activities: 1,N6-Ethenonicotinamide Adenine
      Dinucleotide (epsilon-NAD) and Nicotinamide Guanine Dinucleotide (NGD)
      Fluorescence-based Methods.
AB  - CD38 is a multifunctional enzyme involved in calcium signaling and Nicotinamide
      Adenine Dinucleotide (NAD+) metabolism. Through its major activity, the
      hydrolysis of NAD+, CD38 helps maintain the appropriate levels of this molecule
      for all NAD+-dependent metabolic processes to occur. Due to current advances and
      studies relating NAD+ decline and the development of multiple age-related
      conditions and diseases, CD38 gained importance in both basic science and
      clinical settings. The discovery and development of strategies to modulate its
      function and, possibly, treat diseases and improve health span put CD38 under the
      spotlights. Therefore, a consistent and reliable method to measure its activity
      and explore its use in medicine is required. We describe here the methods how our
      group measures both the hydrolase and cyclase activity of CD38, utilizing a
      fluorescence-based enzymatic assay performed in a plate reader using 1,N6
      Ethenonicotinamide Adenine Dinucleotide (epsilon-NAD) and Nicotinamide Guanine
      Dinucleotide (NGD) as substrates, respectively.

PMID- 30112428
TI  - Data on spatio-temporal patterns of wild fruit harvest from the economically
      important palm Mauritia flexuosa in the Peruvian Amazon.
AB  - These data are the foundation of the analyses and results published in the
      article "Spatio-temporal patterns of Mauritia flexuosa fruit extraction in the
      Peruvian Amazon: Implications for conservation and sustainability" (Horn et al.,
      2018) [1]. Here we include data on the volume of M. flexuosa fruit arriving in
      the city of Iquitos, Peru from the surrounding region. This includes the amount
      of fruit (in sacks and kg), the date of entry into Iquitos, the point of
      embarkation (watershed and coordinates), the method of transportation and the
      point of entry into Iquitos. Data is provided in a number of formats, including
      data tables, Google Earth KML files and summary tables by watershed and/or month.

PMID- 30112429
TI  - Modelling intercity accessibility surfaces through different transport modes in
      the Yangtze River Delta mega-region, China.
AB  - The paper presents the data that is related in the research paper entitled "High
      speed rail network development and winner and loser cities in megaregions: The
      case study of Yangtze River Delta, China" (Wang and Duan, in press) [1]. This
      data article describes the modelling results of spatially continuous
      accessibility surfaces through transport modes of the highway, conventional rail
      and high-speed rail networks in the Yangtze River Delta mega-region, China. By
      using a door-to-door approach to integrate intra- and inter-city travel, the data
      is stimulated in the geographic information system environment. It is calculated
      by the datasets of transport networks, land-use types and transport speeds which
      are mainly collected from the OpenStreetMap and GlobeLand30 and relevant design
      specifications on transport infrastructures, respectively. The data is stored in
      raster format and provides high spatial resolution at 100 m. The data can be used
      as a baseline in the studies of transport economics and planning.

PMID- 30112430
TI  - Design of testbed and preliminary data for de-icing experiments using
      piezoelectric actuators.
AB  - The piezoelectric actuators, providing mechanical energy, are a good option to
      remove the ice efficiently. Therefore, a testbed for experiments are designed and
      the preliminary data of de-icing phenomena is provided. An ice specimen, formed
      from sterilized distilled water under -30  degrees C, is detached from the base
      materials after the voltage signal is engaged. The parameterized detachment
      phenomena and the analysis data are presented. The independent variables are ice
      thickness and frequency of the voltage input. The detachment distance is
      presented depending on the independent variables.

PMID- 30112431
TI  - Datasets on the challenges of forced displacement and coping strategies among
      displaced women in selected Internally Displaced Persons' (IDPs) camps in
      Nigeria.
AB  - The phenomenon of internal displacement has always existed. It however became the
      subject of significant concern for the international community since after World
      War 2, with the violation of the human rights of the displaced arising mostly
      from the intensification of intra-state wars around the world. The article
      presented an integrated data on the problems of forced displacement and adopted
      coping strategies among displaced women in selected IDPs camps in Nigeria. The
      study used a qualitative approach with a descriptive survey to explain the major
      problems of forced displacement. The population included women and focus group
      discussion (FGD) guide was adopted to elicit responses from the study population.
      Data was described with the use of a 3-D Chart and the data-set is broadly
      available for further investigation. The findings identified lack of adequate
      care and financial lack as the major challenges affecting displaced women while
      economic opportunities was the most significant coping strategy. It was
      recommended that government and intervening humanitarian agencies will
      consistently adopt reliable legal and institutional framework for the management
      of internal displacement and displaced victims in Nigeria.

PMID- 30112432
TI  - Data based investigation of the energy metering type, billing and usage of
      sampled residents of Ota Community in Nigeria.
AB  - Accurate energy metering and billing is a challenge in some developing countries.
      In Nigeria, the issues of inadequate power generation, transmission and
      distribution infrastructure are recurrent problems, coupled with inefficient
      energy metering which is a major problem that results in residential energy
      consumers being billed unfair energy charges by the Electricity Distribution
      Companies (DISCOs) for unused energy, and this has been termed "crazy bill". For
      the energy sector to be effective, energy bills should be based on the actual
      energy usage and likewise customers must pay for used energy. To achieve this,
      the Nigerian Electricity Regulatory Commission (NERC) recommended the
      installation of prepaid meters for all customers, but as at today, there is no
      full compliance with this regulation. Power supply is grossly unreliable, and
      this has affected power quality due to frequent load shedding and power outages.
      The dataset presented in this article captures the type of apartment, the type of
      electrical appliances used by occupant, the average monthly energy bill paid for
      electricity, the use or non-use of alternative energy sources, the type of
      alternative energy sources used, and the type of energy meter used by sampled
      residents of the Ota community in Ogun State, Nigeria. The dataset was acquired
      using an investigative questionnaire to survey the residential consumers within
      the sampled space.

PMID- 30112433
TI  - Data on the removal of heavy metals from aqueous solution by adsorption using
      melanin nanopigment obtained from marine source: Pseudomonas stutzeri.
AB  - Heavy metals are one of deadly contaminants in ground water across the globe.
      Thus, herein, this data set comprises experimental and modelled data on the
      removal of heavy metals from ground water using melanin synthesized by the marine
      bacteria Pseudomonas stutzeri. Characterization of biosynthesized melanin and
      modelling of the kinetic and the thermodynamic study on adsorption of heavy
      metals such as mercury (Hg(II)), lead (Pb(II)), chromium (Cr(VI)), and copper
      (Cu(II)) are included in this article. Apart from the study of parameters
      involved in adsorption such as pH, temperature, concentration and time; the data
      from these studies are modelled to analyze the nature and characteristic of heavy
      metals adsorbing to melanin nanoparticles. The figures from models, results from
      models as tables, characterization and analytical figures are depicted in this
      work.

PMID- 30112427
TI  - Linguistic Aspects of Primary Progressive Aphasia.
AB  - Primary progressive aphasia (PPA) refers to a disorder of declining language
      associated with neurodegenerative diseases such as frontotemporal degeneration
      and Alzheimer disease. Variants of PPA are important to recognize from a medical
      perspective because these syndromes are clinical markers suggesting specific
      underlying pathology. In this review, I discuss linguistic aspects of PPA
      syndromes that may prove informative for parsing our language mechanism and
      identifying the neural representation of fundamental elements of language. I
      focus on the representation of word meaning in a discussion of semantic variant
      PPA, grammatical comprehension and expression in a discussion of
      nonfluent/agrammatic variant PPA, the supporting role of short-term memory in a
      discussion of logopenic variant PPA, and components of language associated with
      discourse in a discussion of behavioral variant frontotemporal dementia. PPA
      provides a novel perspective that uniquely addresses facets of language and its
      disorders while complementing traditional aphasia syndromes that follow stroke.

PMID- 30112434
TI  - Equilibrium data for the cross-metathesis of methyl oleate with cinnamaldehyde.
AB  - Here we present equilibrium data for the cross-metathesis of methyl oleate (MO)
      with cinnamaldehyde (CA) obtained experimentally from liquid-phase catalytic
      tests conducted at 323 K. The reaction was carried out in batch reactors, using
      different reactant molar ratios and the 2nd generation Ru Hoveyda-Grubbs complex
      as catalyst. Reaction mixtures at the equilibrium were analyzed by gas
      chromatography. Equilibrium constants were determined by assuming unitary
      activity coefficients for a cinnamaldehyde/methyl oleate equimolar ratio, and the
      validity of that approximation was evaluated by calculating the equilibrium
      conversions for different reactant molar ratios.

PMID- 30112435
TI  - Data on preschool children's math, patterning, and spatial knowledge.
AB  - Initial participants were 79 children who were recruited from six preschool
      programs in the U.S. Full assessment data was available for 73 children (average
      age of 4 years 7 months), including demographic data (gender, ethnicity,
      financial need, language(s) spoken at home and special education status).
      Children's math, repeating patterning, spatial and verbal skills were assessed at
      the beginning of the pre-kindergarten year. Assessments included the brief
      version of the Research-Based Early Mathematics Assessment, two measures of
      repeating patterning skills, three measures of spatial skills (the Block Design
      subtest of the Wechsler Preschool and Primary Scale of Intelligence, the Position
      in Space subtest of the Developmental Test of Visual Perception, and a Corsi
      Block Tapping Task), the Picture Vocabulary Test from the NIH Toolbox app and a
      backward letter span task. Near the end of the school year, their math knowledge
      was re-assessed using the same math measure, as was their memory span (forward
      and backward digit span task from the Wechsler Intelligence Scale for Children).
      Findings on the relations between patterning, spatial and math skills are
      published elsewhere (Rittle-Johnson et al., 2018) [1].

PMID- 30112436
TI  - Antibody-Drug Conjugates in Bladder Cancer.
AB  - Urothelial carcinoma (UC) is characterized by expression of a plethora of cell
      surface antigens, thus offering opportunities for specific therapeutic targeting
      with use of antibody-drug conjugates (ADCs). ADCs are structured from two major
      constituents, a monoclonal antibody (mAb) against a specific target and a
      cytotoxic drug connected via a linker molecule. Several ADCs are developed
      against different UC surface markers, but the ones at most advanced stages of
      development include sacituzumab govitecan (IMMU-132), enfortumab vedotin (ASG
      22CE/ASG-22ME), ASG-15ME for advanced UC, and oportuzumab monatox (VB4-845) for
      early UC. Several new targets are identified and utilized for novel or existing
      ADC testing. The most promising ones include human epidermal growth factor
      receptor 2 (HER2) and members of the fibroblast growth factor receptor axis
      (FGF/FGFR). Positive preclinical and early clinical results are reported in many
      cases, thus the next step involves further improving efficacy and reducing
      toxicity as well as testing combination strategies with approved agents.

PMID- 30112437
TI  - Systematic Review: An Update on the Spectrum of Urological Malignancies in Lynch
      Syndrome.
AB  - Background: Lynch syndrome is an autosomal dominant disorder that predisposes
      individuals affected to certain malignancies. Colon and endometrial cancers are
      the malignancies most highly associated with Lynch syndrome. However, growing
      body of evidence links Lynch syndrome to urological cancers. Objective: This
      review aims to clarify the type of urological malignancies that fall under the
      Lynch-associated cancer spectrum. Methods: Using PRISMA guidelines, a systematic
      search between January 1990 to February 2018, was conducted using the MEDLINE
      database with the application of the following MESH terms: colorectal neoplasms,
      hereditary nonpolyposis; DNA mismatch repair; urologic neoplasms; kidney pelvis;
      ureteral neoplasms; urinary bladder; carcinoma, transitional cell; prostatic
      neoplasms; testicular neoplasms. Results: Upper tract urothelial cancers are well
      established under the Lynch spectrum. Increasing evidence supports its
      association with prostate cancer. However, there is, inconclusive and limited
      evidence for an association with bladder and testicular cancer. Conclusions: The
      evidence underpinning certain urological malignancies associated with Lynch
      syndrome has expanded in recent years. Our review may assist in providing a
      summary of the current standing in literature. However, we recommend further
      investigations to better clarify associations, particularly with prostate,
      bladder and testicular cancer.

PMID- 30112438
TI  - A Gene Expression Signature Predicts Bladder Cancer Cell Line Sensitivity to EGFR
      Inhibition.
AB  - Background: Bladder cancer remains a cancer type in need of novel and alternative
      therapies. While multiple inhibitors of EGFR have been evaluated for efficacy in
      bladder cancer, the results have largely been disappointing with few patients
      responding to these therapies. Yet, there is a subset of patients that positively
      responds to EGFR inhibition with tumor shrinkage, indicating it is an effective
      treatment for a targeted set of bladder tumors. Objective: To derive a gene
      expression signature capable of predicting the response to EGFR inhibition in
      bladder cancer cell lines. Methods: he response to cetuximab for 68 colorectal
      cancer patients was used as training data to generate a gene expression
      signature. We applied this signature to bladder cancer cell lines and predictions
      were compared to the responses to seven EGFR inhibitors. Results: A novel 67-gene
      signature derived from colorectal cancer was able to significantly identify
      bladder cancer cell lines by their response to several EGFR inhibitors.
      Conclusions: The 67-gene signature can determine bladder cancer cell line
      sensitivity to EGFR inhibition. This work demonstrates a preclinical strategy to
      identify bladder cancer cell lines for EGFR-targeted therapy.

PMID- 30112439
TI  - Fatty Acid Patterns Detected By Ambient Ionization Mass Spectrometry in Canine
      Invasive Urothelial Carcinoma From Dogs of Different Breeds.
AB  - Background: In early work ambient ionization mass spectrometry (MS) revealed
      lipid patterns distinguishing muscle invasive bladder cancer (invasive urothelial
      carcinoma, InvUC) from normal urothelium. A new ambient ionization MS approach,
      touch spray MS (TS-MS) can rapidly generate mass spectra in real time,
      potentially in a point-of-care setting. A tissue sample removed from a patient is
      touched by a probe, and mass spectra generated within seconds. Objective: To
      validate TS-MS methods using specimens from naturally-occurring InvUC in dogs
      where the cancer closely mimics the human condition, and to demonstrate proof-of
      concept that TS-MS can elucidate lipid patterns distinguishing InvUC from normal
      urothelium. Methods: Samples of normal urothelium and InvUC from dogs of several
      breeds were analyzed by TS-MS with correlative histopathology across each sample.
      Results were compared to those obtained with desorption electrospray ionization
      mass spectrometry (DESI-MS), a more traditional method. Data were analyzed by
      Principal Component Analysis and Linear Discriminant Analysis. Results: Lipid
      patterns identified by TS-MS, as well as by DESI-MS, differed between InvUC and
      normal urothelium with m/z 281.5 (oleic acid) and m/z 563.5 (oleic acid dimer)
      substantially contributing to the differences. Using histologic diagnosis as the
      gold standard, TS-MS had a global prediction rate of 93%. Conclusions: TS-MS can
      be used to identify lipid patterns that differentiate canine InvUC from normal
      urothelium. Optimization of TS-MS could lead to a point-of-care approach to
      distinguish cancer from normal in ex vivo tissues in real time, and to define
      biochemical processes leading to cancer development and progression.

PMID- 30112440
TI  - Double-Blind, Randomized, Placebo-controlled Studies Evaluating Apaziquone (E09,
      QapzolaTM) Intravesical Instillation Post Transurethral Resection of Bladder
      Tumors for the Treatment of Low-risk Non-Muscle Invasive Bladder Cancer.
AB  - Background: Guidelines recommend a single postoperative instillation of
      intravesical chemotherapy within 24 hours of transurethral resection of bladder
      tumors (TURBT) in patients with low- and intermediate-risk non-muscle invasive
      bladder cancer (NMIBC) to reduce recurrence risk. Objective: To evaluate the 2
      year recurrence rate (2-YRR) of bladder cancer in randomized patients with Ta, G1
      G2 histology who receive TURBT plus apaziquone versus TURBT plus placebo.
      Methods: Two nearly identical Phase 3, multinational, randomized, double-blind,
      placebo-controlled trials were conducted in patients with histologically
      confirmed Ta, G1-G2 NMIBC (Target Population) to evaluate the efficacy/safety of
      a single instillation of apaziquone post-TURBT. A single intravesical
      instillation of apaziquone (4 mg/40 mL) or placebo was administered within 6
      hours post-TURBT. The primary and secondary efficacy endpoints were 2-YRR and
      time to recurrence (TTR) respectively. Results: Overall, 1614 patients were
      enrolled, including 1146 patients in the Target Population. Individually, the two
      studies did not meet statistical significance for 2-YRR (38.0% vs 44.6% ; 39.7%
      vs. 46.3%). Because apaziquone is rapidly metabolized in blood, a post hoc
      subgroup analysis was performed by time window of drug instillation post-TURBT.
      Patients who had drug instilled in the time window 60+/-30 minutes post-TURBT
      demonstrated 20.3% and 20.8% reduction in 2-YRR and 56% (HR = 0.44) and 45% (HR =
      0.55) reduction in hazards for TTR in two studies respectively. Apaziquone was
      well tolerated with minimal toxicity. Conclusions: Two identical Phase 3 studies
      supported the safety of apaziquone (4 mg/40 mL) administered as a single
      intravesical instillation post-TURBT and identified efficacy when instilled
      within 60+/-30-minutes time interval which requires further study.

PMID- 30112441
TI  - Total Fluid Intake and the Risk of Recurrence in Patients With Non-Muscle
      Invasive Bladder Cancer: A Prospective Cohort Study.
AB  - Objectives: To investigate the role of fluid intake from beverages before and
      after a diagnosis of bladder cancer in relation to the risk of developing bladder
      cancer recurrence. Study Design: Prospective cohort study. Methods: 716 patients
      with non-muscle invasive bladder cancer (NMIBC), who received transurethral
      resection of a primary bladder tumour (TURBT) and completed self-administrated
      questionnaires on usual fluid intake from beverages at time of diagnosis (over
      the year before diagnosis) and during follow-up (over the year after diagnosis),
      were included. Multivariable Cox regression was used to calculate hazard ratios
      and 95% confidence intervals of developing recurrent bladder cancer in relation
      to the intake of total fluid, total alcohol, and individual beverages. Results:
      During 2,025 person-years of follow-up, 238 (33%) of the included 716 NMIBC
      patients developed one or more recurrences of bladder cancer. Total fluid intake
      before diagnosis was not associated with a first recurrence of bladder cancer
      when comparing the highest and lowest intake group (HR = 0.98, 95% C.I. 0.70
      1.38, p = 0.91). Comparable results were obtained for total fluid intake pre
      diagnosis and the risk of developing multiple recurrences of bladder cancer (HR =
      1.01, 95% C.I. 0.87-1.19, p = 0.85). A total of 379 of the 716 patients reported
      on usual fluid intake within 1 year of diagnosis. No significant associations
      between total fluid intake 1 year after diagnosis and a first recurrence of
      bladder cancer were found when comparing the highest and lowest intake group (HR
      = 0.91; 95% C.I. 0.60-1.37, p = 0.65) or with multiple recurrences of bladder
      cancer (HR = 1.06; 95% C.I. 0.89-1.26, p = 0.54). In addition, total alcohol
      intake and individual beverages were not associated with bladder cancer
      recurrence. Conclusions: The results indicate that an individual's fluid intake
      from beverages is unlikely to have an important role in bladder cancer
      recurrence.

PMID- 30112442
TI  - Radiation Therapy as Definitive Local Treatment in Patients with Limited-Stage
      Small Cell Carcinoma of the Bladder: Does total dose matter?
AB  - Purpose: To determine whether total radiation dose affects survival outcomes for
      patients with small cell carcinoma of the bladder (SCCB). Methods: We queried the
      National Cancer Database (NCDB) for patients with limited stage SCCB undergoing
      multimodality treatment and retrospectively analyzed survival outcomes according
      to total radiation dose received. Results: Patients aged 41-79 receiving a total
      radiation dose of 54 Gy or greater had a significant improvement in overall
      survival compared to those receiving less than 54 Gy, with a median overall
      survival of 58.9 months (95% confidence interval [CI] 37.2-80.6 months) compared
      to 21.5 months (95% CI 15.2 -27.8 months) (p < 0.05). There was no difference in
      outcomes for patients receiving between 54 and 60 Gy compared to those receiving
      60 Gy or higher. There was also no difference in outcomes based on total
      radiation dose for patients 80 years and older. Conclusions: For patients aged 79
      or younger with limited stage SCCB, total radiation dose of 54 Gy or greater is
      associated with better overall survival.

PMID- 30112443
TI  - Systematic Review: Depression and Anxiety Prevalence in Bladder Cancer Patients.
AB  - Background: Depression affects more than 300 million people of all ages
      worldwide. In patients with cancer the reported prevalence is up to 24%.
      Objective: To systematically review the literature to report the prevalence of
      depression and anxiety among patients with bladder cancer (BC). Methods: Web of
      Science, MEDLINE/PubMed, and The Cochrane Library were searched between January
      and March 2018 using the terms "bladder carcinoma OR bladder cancer AND
      depression OR anxiety". Results: Thirteen studies encompassing 1659 patients with
      BC were included. Six studies assessed depression prior and after treatment at 1,
      6 and 12 months. Three were conducted in the US, one each in Turkey, Sweden/Egypt
      and China. Four studies showed a reduction of depression after radical cystectomy
      (RC) at 1, 6 and 12 months, respectively. Contrary, two studies showed no
      significant difference in depression between baseline and follow-up. Four studies
      investigated anxiety; they reported a slight reduction in anxiety score compared
      to baseline. Seven additional studies reported the prevalence of depression and
      anxiety (five studies) among patients with BC at a specific time-point. Studies
      were conducted in Sweden (2), Italy, Greece, US, China and Spain. Pretreatment
      depression rates ranged from 5.7 to 23.1% and post-treatment from 4.7 to 78%.
      Post-treatment anxiety rates ranged from 12.5 to 71.3%. Conclusions: The
      prevalence of reported depression and anxiety among BC patients is high with
      large geographic heterogeneity. Gender and geriatric specific screening and
      management for anxiety and depression should be implemented to alleviate
      suffering.

PMID- 30112445
TI  - New Horizons in Bladder Cancer Research: Report of the 15th Meeting of the
      International Bladder Cancer Network (IBCN) in Lisbon, Portugal, October 21-23,
      2017.

PMID- 30112444
TI  - Low Frequency of Intratumor Heterogeneity in Bladder Cancer Tissue Microarrays.
AB  - Background: Intratumoral heterogeneity (ITH) is associated with clinical
      challenges such as possible differences in response to treatment and difficulties
      in classifying the tumor. Previously, ITH has been described in bladder cancer
      using detailed genetic analyses. However, in this disease, it is not known to
      what extent ITH actually occurs, or if it involves molecular subtyping, when
      assessment is achieved by immunohistochemistry (IHC) on the protein level using
      tissue microarrays (TMAs), the method most widely applied when analyzing large
      sample numbers. Objective: We aimed to investigate ITH by IHC in bladder cancer
      TMAs. Methods: Staining for eleven immunohistochemical markers (CK5, Cyclin D1, E
      Cadherin, EGFR, FGFR, GATA3, HER2, p16, p63, P-Cadherin and RB1) was performed,
      and differences in staining patterns were assessed both within 1981 individual
      tissue-cores and by comparing two cores from the same tumor in 948 cases
      according to our pre-specified criteria. Presence of ITH was associated with
      clinicopathological data such as stage, grade, molecular subtype and survival.
      Results: Intracore ITH in one or several markers was associated with grade 3,
      stage T1 and the genomically unstable molecular subtype. ITH in three or more
      markers was found in 5% between cores (intercore heterogeneity) and in 2% within
      cores (intracore heterogeneity). No association with survival was found for any
      of the ITH groups. Conclusions: We observed ITH in a small proportion of the
      tumors, suggesting that ITH has only a limited impact on TMA bladder cancer
      studies.

PMID- 30112446
TI  - Challenging Cases in Urothelial Cancer.

PMID- 30112447
TI  - Clinical Trials Corner.

PMID- 30112448
TI  - Financial Toxicity of Having Bladder Cancer.

PMID- 30112450
TI  - Pityriasis rubra pilaris-like erythroderma in the setting of pembrolizumab
      therapy responsive to acitretin.

PMID- 30112449
TI  - Clinico-dermoscopic features of alopecia areata in patients with psoriasis.

PMID- 30112451
TI  - Cutaneous thrombotic vasculopathy related to poorly controlled ulcerative
      colitis.

PMID- 30112452
TI  - Checkpoint inhibitor-associated cutaneous small vessel vasculitis.

PMID- 30112453
TI  - Neglected basal cell carcinoma presenting with diffuse skeletal metastases.

PMID- 30112454
TI  - Potential for overlooked melanoma in solid organ donors with a severely
      dysplastic nevus.

PMID- 30112456
TI  - Highway paving in the southwestern Amazon alters long-term trends and drivers of
      regional vegetation dynamics.
AB  - Infrastructure development, specifically road paving, contributes socio-economic
      benefits to society worldwide. However, detrimental environmental effects of road
      paving have been documented, most notably increased deforestation. Beyond
      deforestation, we hypothesize that road paving introduces "unseen" regional scale
      effects on forests, due to changes to vegetation dynamics. To test this
      hypothesis, we focus on the tri-national frontier in the southwestern Amazon that
      has been subject to construction of the Inter-Oceanic Highway (IOH) between 1987
      and 2010. We use a long-term remotely sensed vegetation index as a proxy for
      vegetation dynamics and combine these with field-based socio-ecological data and
      biophysical data from global datasets. We find 4 areas of shared vegetation
      dynamics associated with increasing extent of road paving. Applying Dynamic
      Factor Analysis, an exploratory dimension-reduction time series analysis
      technique, we identify common trends and covariates in each area. Common trends,
      indicating underlying unexplained effects, become relatively less important as
      paving increases, and covariates increase in importance. The common trends are
      dominated by lower frequency signals possibly embodying long-term climate
      variability. Human-related covariates become more important in explaining
      vegetation dynamics as road paving extent increases, particularly family density
      and travel time to market. Natural covariates such as minimum temperature and
      soil moisture become less important. The change in vegetation dynamics identified
      in this study indicates a possible change in ecosystem services along the
      disturbance gradient. While this study does not include all potential factors
      controlling dynamics and disturbance of vegetation in the region, it offers
      important insights for management and mitigation of effects of road paving
      projects. Infrastructure planning initiatives should make provisions for more
      detailed vegetation monitoring after road completion, with a broader focus than
      just deforestation. The study highlights the need to mitigate population-driven
      pressures on vegetation like family density and access to new markets.

PMID- 30112455
TI  - Characterization of Two Arabidopsis L-Gulono-1,4-lactone Oxidases, AtGulLO3 and
      AtGulLO5, Involved in Ascorbate Biosynthesis.
AB  - L-Ascorbic acid (AsA, vitamin C) is an essential antioxidant for plants and
      animals. There are four known ascorbate biosynthetic pathways in plants: the L
      galactose, L-gulose, D-galacturonate, and myo-inositol routes. These pathways
      converge into two AsA precursors: L-galactono-1,4-lactone and L-gulono-1,4
      lactone (L-GulL). This work focuses on the study of L-gulono-1,4-lactone oxidase
      (GulLO), the enzyme that works at the intersect of the gulose and inositol
      pathways. Previous studies have shown that feeding L-gulono-1,4-lactone to
      multiple plants leads to increased AsA. There are also reports showing GulLO
      activity in plants. We describe the first detailed characterization of a plant
      enzyme specific to oxidize L-GulL to AsA. We successfully purified a recombinant
      Arabidopsis GulLO enzyme (called AtGulLO5) in a transient expression system. The
      biochemical properties of this enzyme are similar to the ones of bacterial
      isozymes in terms of substrate specificity, subcellular localization, use of
      flavin adenine dinucleotide (FAD) as electron acceptor, and specific activity.
      AtGulLO5 is an exclusive dehydrogenase with an absolute specificity for L-GulL as
      substrate thus differing from the existing plant L-galactono-1,4-lactone
      dehydrogenases and mammalian GulLOs. Feeding L-GulL to N. benthamiana leaves
      expressing AtGulLO5 constructs led to increased foliar AsA content, but it was
      not different from that of controls, most likely due to the observed low
      catalytic efficiency of AtGulLO5. Similar results were also obtained with another
      member of the AtGulLO family (AtGulLO3) that appears to have a rapid protein
      turnover. We propose that AsA synthesis through L-GulL in plants is regulated at
      the post-transcriptional level by limiting GulLO enzyme availability.

PMID- 30112458
TI  - Probabilistic analysis and resistance factor calibration for deep foundation
      design using Monte Carlo simulation.
AB  - The method of incorporating the sources of parameter uncertainty is crucial when
      conducting probabilistic analysis for service limit state (SLS) design of a deep
      foundation. This paper describes the method of using Monte Carlo simulation for
      probabilistic analyses and for calibration of resistance factors of drilled
      shafts at SLS. The paper presents discussions on the finding of an impossible
      case, where the different combinations of load, variability of soil strength and
      target probability of failure made it impossible to calibrate the SLS resistance
      factors. Resistance factors for drilled shafts in shale are introduced, and were
      found to be responsive to load levels. The higher load level, the lower the
      resistance factor. These findings help smooth the transition from allowable
      stress design to load and resistance factor design for geotechnical engineers.

PMID- 30112457
TI  - Bacterial diversity and production of sulfide in microcosms containing
      uncompacted bentonites.
AB  - Aims: This study examined the diversity and sulfide-producing activity of
      microorganisms in microcosms containing commercial clay products (e.g., MX-80,
      Canaprill and National Standard) similar to materials which are currently
      considered for use in the design specifications for deep geologic repositories
      (DGR) for spent nuclear fuel. Methods and results: In anoxic microcosms incubated
      for minimum of 60 days with 10 g l-1 NaCl, sulfide production varied with
      temperature, electron donor and bentonite type. Maximum specific sulfide
      production rates of 0.189 d-1, 0.549 d-1 and 0.157 d-1 occurred in lactate-fed MX
      80, Canaprill and National Standard microcosms, respectively. In microcosms with
      50 g l-1 NaCl, sulfide production was inhibited. Denaturing gradient gel
      electrophoresis (DGGE) profiling of microcosms revealed the presence of bacterial
      classes Clostridia, Bacilli, Gammaproteobacteria, Deltaproteobacteria,
      Actinobacteria, Sphingobacteriia and Erysipelotrichia. Spore-forming and non
      spore-forming bacteria were confirmed in microcosms using high-throughput 16S
      rRNA gene sequencing. Sulfate-reducing bacteria of the genus Desulfosporosinus
      predominated in MX-80 microcosms; whereas, Desulfotomaculum and Desulfovibrio
      genera contributed to sulfate-reduction in National Standard and Canaprill
      microcosms. Conclusions: Commercial clays microcosms harbour a sparse bacterial
      population dominated by spore-forming microorganisms. Detected sulfate- and
      sulfur-reducing bacteria presumably contributed to sulfide accumulation in the
      different microcosm systems. Significance and impact of study: The use of carbon
      supplemented, clay-in-water microcosms offered insights into the bacterial
      diversity present in as-received clays, along with the types of metabolic and
      sulfidogenic reactions that might occur in regions of a DGR (e.g., interfaces
      between the bulk clay and host rock, cracks, fissures, etc.) that fail to attain
      target parameters necessary to inhibit microbial growth and activity.

PMID- 30112459
TI  - Investigation on the variation law of gas liquid solid three phase boundary in
      porous gas diffusion electrode.
AB  - The three-phase boundary length will change with the electrochemical reaction in
      the working process of the gas diffusion electrode. The process of porous media
      fluid interface movement is investigated by establishing the physical and
      mathematical model of the microporous electrode. Using a numerical simulation
      method, the electrode section electron micrographs are topologically gridded to
      investigate the micro flow phenomenon of the gas diffusion electrode in the zinc
      air battery. By simulating the development process of the electrolyte interface
      in the porous electrode, the law for the variation of the total length of the
      three-phase boundary is observed. The results show that the total length of the
      three-phase boundary increases first and then shortens with the change of gas
      diffusion and electrolyte electrode movement. A similar trend is observed when
      the peak power is varied. A theoretical expression for that defines the changes
      in the length of the three-phase boundary is provided. Finally, we show that the
      topology and the grid method are feasible means that can be used to analyze
      electrochemical reactions in complex multiphase flows.

PMID- 30112461
TI  - A fatal case of Susac syndrome: The importance of ophthalmic examination in
      confirming the diagnosis.
AB  - Purpose: To report a fatal case of Susac syndrome in a 24-year-old female.
      Observations: A 24-year-old female presented with progressive encephalopathy of
      unknown etiology. Her previous evaluation consisted of laboratory testing,
      imaging, and a brain biopsy to investigate for infectious and rheumatologic
      diseases. Several months after onset of symptoms, she underwent ophthalmic
      examination, which demonstrated bilateral branch retinal artery occlusions.
      Further review of her medical record revealed a recent history of hearing loss.
      Based on the retinal and systemic findings, the patient was diagnosed with Susac
      syndrome. The patient was started on intensive immunosuppression; however, she
      became more obtunded and succumbed several months after her diagnosis.
      Conclusions and importance: The timely and accurate diagnosis of Susac syndrome,
      which classically manifests as the triad of encephalopathy, vestibulocochlear
      abnormalities, and retinal arteriolar occlusions, may help to reduce the
      morbidity of invasive testing and to prevent fatality.

PMID- 30112462
TI  - An Analysis of Whether Health Literacy and Numeracy Are Associated with Diabetes
      Medication Adherence.
AB  - Many people with type 2 diabetes do not take medications as prescribed, resulting
      in suboptimal glycemic control and a greater risk of diabetes complications.
      Taking medications regularly requires adequate health literacy and numeracy
      skills, but associations between health literacy and numeracy skills and
      medication taking are mixed. We used validated, reliable, and widely accepted
      measures to examine the relationship between health literacy, numeracy, and
      medication adherence among a sample of patients with T2D. We analyzed cross
      sectional data using non-parametric Mann-Whitney U-tests and unadjusted and
      adjusted logistic regression models. For every one point increase on the Brief
      Health Literacy Screen and Subjective Numeracy Scale, participants were 1.8 and
      2.7 times more likely to optimally take medications (p < 0.05). Health literacy
      and numeracy skills should be considered in the design of education materials for
      medication management and adherence among people with T2D.

PMID- 30112460
TI  - Factors associated with clinical trials that fail and opportunities for improving
      the likelihood of success: A review.
AB  - Clinical trials are time consuming, expensive, and often burdensome on patients.
      Clinical trials can fail for many reasons. This survey reviews many of these
      reasons and offers insights on opportunities for improving the likelihood of
      creating and executing successful clinical trials. Literature from the past 30
      years was reviewed for relevant data. Common patterns in reported successful
      trials are identified, including factors regarding the study site, study
      coordinator/investigator, and the effects on participating patients. Specific
      instances where artificial intelligence can help improve clinical trials are
      identified.

PMID- 30112463
TI  - Endoplasmic Reticulum-Vacuole Contact Sites "Bloom" With Stress-Induced Lipid
      Droplets.
AB  - Lipid droplets (LDs) serve as specialized cytoplasmic organelles that harbor
      energy-rich lipids for long-term storage and may be mobilized as nutrient sources
      during extended starvation. How cells coordinate LD biogenesis and utilization in
      response to fluctuations in nutrient availability remains poorly understood.
      Here, we discuss our recent work revealing how yeast spatially organize LD
      budding at organelle contacts formed between the endoplasmic reticulum and yeast
      vacuole/lysosome (sites known as nucleus-vacuole junctions [NVJs]). During times
      of imminent nutrient exhaustion, we observe blooms of stress-induced LDs
      surrounding the NVJ and find that this LD clustering is regulated by NVJ-resident
      protein Mdm1. We also discuss several emerging studies revealing specific
      proteins that demarcate a subpopulation of NVJ-associated LDs. Collectively,
      these studies reveal a previously unappreciated role for the spatial
      compartmentalization of LDs at organelle contacts and highlight an important role
      for interorganellar cross talk in LD dynamics under times of nutritional stress.

PMID- 30112464
TI  - Developing a Public Health Pipeline: Key Components of a Public Health Leadership
      Program.
AB  - Thirty percent of federal public health employees were retirement eligible in
      September 2017. Further, at the state public health level, as indicated in the
      recent Public Health Workforce Interests and Needs Survey (PH WINS), an estimated
      25% of employees are planning to retire before 2020 with an additional 18%
      intending to leave their organizations within one year. Due to these workforce
      changes, there is an urgent need for public health organizations to examine how
      they are ensuring a talent pool from which leaders can emerge. As a large federal
      public health agency, the Centers for Disease Control and Prevention (CDC) faces
      the challenge of providing leadership development to staff. Factors were examined
      that agency leaders identified as key components of a leadership development
      program to transition scientific public health staff into supervisory leadership
      roles. While many factors contribute to leadership development, participants more
      often identified training, provision of opportunities, mentors, and
      identification of high potential employees as key components of a leadership
      develop program. With the need to develop organizational leaders to be ready when
      vacancies become available, findings from this study can inform the development
      and implementation of public health leadership development programs.

PMID- 30112465
TI  - Evaluation of Enamel Surface Roughness after Various Finishing Techniques for
      Debonding of Orthodontic Brackets.
AB  - Objective: The aim of this study was to evaluate the surface roughness of enamel
      after debonding with various types of burs. Methods: The buccal surfaces of 20
      mandibular incisors for each group of bur were subjected to profilometer
      analysis, and three parameters of surface irregularity were recorded. After
      bracket debonding, adhesive remnants were removed by tungsten carbide burs in low
      speed, high-speed, and stainbuster settings. The samples were evaluated at pre
      treatment (on sound enamel) (T1) and post-treatment (T2) by a profilometer. The
      specimens were measured twice, and the mean values were recorded. Results: The
      results were analyzed in intra-group comparisons with paired t-tests and in inter
      group comparisons with one-way ANOVA and Tukey's HSD test. All resin removal
      techniques significantly increased enamel surface roughness (p<0.05). According
      to one-way ANOVA, there were significant differences in the effect of enamel
      surface roughness between all methods (p<0.05). The high-speed bur caused the
      maximum roughness values and the stainbuster bur caused the minimum roughness
      values in all the parameters (Ra, Rz, and Rq). Conclusion: The three types of
      burs used for finishing methods revealed significant differences in the enamel
      surface after debonding. However, the stainbuster bur created smoother surfaces
      than the other applied methods.

PMID- 30112466
TI  - Does the Seating Force Affect the Shear Bond Strength of Brackets? An InVitro
      Study.
AB  - Objective: The purpose of this study was to observe two different seating forces
      on conventional and self-ligating brackets using shear bond strength (SBS).
      Methods: The study material consisted of 48 recently extracted human premolars
      divided into four groups: Group I, conventional bracket (Master series, AO) 100 g
      seating force applied; Group II, conventional bracket (Master series, AO) 200 g
      seating force applied; Group III, self-ligating bracket (Empower, AO) 100 g
      seating force applied; and Group IV, self-ligating bracket (Empower, AO) 200 g
      seating force applied. All teeth were bonded with Transbond XT by the same
      operator. Following the bonding procedure, all teeth were stored in deionized
      water at 37 degrees C for 30 days, and they were thermal cycled. A universal
      testing machine was used to obtain the SBS records. The Kruskal-Wallis
      statistical test was used to determine the significant differences in SBS between
      the four groups, and the Mann-Whitney U test with Bonferroni correction was used
      to compare the subgroups. Results: The mean shear bond strength was 15.70 MPa for
      Group I, 13.97 MPa for Group II, 8.38 MPa for Group III, and 8.31 MPa for Group
      IV. Significant differences in the SBS values were recorded between the self
      ligating groups and conventional bracket groups. Seating forces on the brackets
      did not show any differences among the groups. Conclusion: Within the limitations
      in this study, 100 g and 200 g forces can be applied because both seating forces
      showed acceptable SBS results.

PMID- 30112467
TI  - The Effect of Educational Status on the Perception of Social and Spontaneous
      Smiles.
AB  - Objective: The aim of the present study was to evaluate the effect of educational
      status on the perception of smile esthetics considering social and spontaneous
      smile patterns. Methods: The present study was conducted on 110 subjects with
      differing educational status. Of 110 subjects with a mean age of 39.4 years, 30
      were primary school graduates, 30 were high school graduates, and 50 had a
      university or higher educational level. Four different black and white natural
      social and spontaneous smiling images, captured from a video recording of a 25
      year-old female, were prepared displaying the full-face and oral area. A 10-cm
      visual analog scale (VAS) was used to evaluate the smile esthetics. Results:
      There were significant differences in the social and spontaneous smiles in a
      subjective assessment of the smile esthetics in full-face and oral views between
      participants having a different educational status (p>0.05). Compared with the
      other groups, the participants in the primary school graduate group gave higher
      esthetic scores in all the image groups. In terms of esthetic perception, this
      group was followed by high school graduates and participants with a university or
      higher level of education. In the four image groups, there was a significant
      difference between the primary school graduates and participants with a
      university or higher level of education (p<0.05). Conclusion: Educational status
      is a sociodemographic factor that can affect the perception of smile esthetics.
      The esthetic scores both in social and spontaneous smile decrease with increasing
      education level, and the most remarkable difference exists between primary school
      graduates and those with university or higher level of education.

PMID- 30112469
TI  - Orthognathic Treatment of Skeletal Class III Malocclusion with Severe Facial
      Asymmetry.
AB  - A 26-year, 9-month-old woman had chief complaints of mandibular protrusion and
      facial asymmetry. Extraoral examination indicated mandibular deviation to the
      left side, severe facial asymmetry, and a concave profile. Because the patient
      had a vertical maxillary height difference and an occlusal plane cant together
      with maxillary retrusion, a differential downgraft and advancement surgery with
      Lefort I osteotomy was planned. To correct the facial asymmetry and mandibular
      protrusion, concurrent bilateral sagittal split osteotomy was performed. Double
      jaw surgical procedures, including maxillary and mandibular movements, are
      effective in correcting severe facial asymmetry and skeletal Class III
      malocclusion.

PMID- 30112468
TI  - Cone Beam Computed Tomography in Orthodontics.
AB  - The advent of three-dimensional (3D) imaging technology has caused a significant
      change in the diagnostic approach practiced in dentistry, and in particular,
      orthodontics. Although conventional imaging methods such as orthopantomography
      and lateral cephalometric and anteroposterior graphs provide sufficient
      information in mild to moderate orthodontic anomalies, 3D imaging can be a
      necessity in severe skeletal anomalies or tooth impactions. Computed tomography
      (CT) has been frequently used when detailed 3D imaging is necessary despite its
      relatively high cost, low vertical resolution, and high dose of radiation. In
      contrast to conventional CT application, the development of cone beam computed
      tomography (CBCT) technology has had important advantages over the conventional
      method, such as minimization of the radiation dose, image accuracy, rapid scan
      time, fewer image artifacts, chair-side image display, and real-time analysis.
      These advantages have provided dental practitioners the opportunity to benefit
      more frequently from 3D imaging by relatively diminishing radiation dose
      considerations, financial burden, and availability, in particular. Therefore, the
      aim of this review is to highlight the current understanding of CBCT practice in
      orthodontics and to summarize clinically relevant conditions.

PMID- 30112470
TI  - Do Different Orthodontic Malocclusions Affect Patients' Self-Concept and
      Psychosocial Status?
AB  - Objective: The aim of this study was to evaluate the self-concept and
      psychosocial status measured by the levels of social phobia and loneliness in a
      sample of adolescent patients with different malocclusions and to explain the
      relationships, if any, between malocclusions. Methods: This study was performed
      on 90 (41 females and 49 males) orthodontic patients with a mean age of 13.52+/
      1.81 years. The patients were divided into three groups (Class I, Class II, and
      Class III) according to the different types of malocclusions. Piers-Harris
      Children's Self-Concept Scale (PHCSCS) was used to determine the self-concepts of
      patients. In addition, the levels of social phobia and loneliness were measured
      by Capa Social Phobia Scale for Children and Adolescents (CSPSCA) and University
      of California Los Angeles (UCLA) Loneliness Inventory, respectively. Data were
      analyzed statistically. The self-concept, social phobia, and loneliness scores of
      each group were compared using two-way analysis of variance (ANOVA) and Tukey's
      post hoc test. Results: Self-concept scores did not significantly differ between
      the groups, except for the popularity subscale. Patients with Class II
      malocclusion had the lowest popularity scores. No significant differences were
      found between the levels of social phobia and loneliness among groups (p>0.05).
      Conclusion: Our findings demonstrated that different malocclusions do not affect
      patients' self-concept and psychosocial well-being.

PMID- 30112471
TI  - Displacement of the Mandibular Condyles Immediately after Herbst Appliance
      Insertion - 3D Assessment.
AB  - Objective: To test the following two hypotheses regarding the consequences of
      Herbst appliance (HA) insertion: 1) a significant clockwise mandibular rotation
      will occur and 2) the displacement of the condyles will follow the same magnitude
      of the changes of overjet (OJ) and overbite (OB). Methods: Virtual 3D surface
      models of 25 patients were generated from cone-beam computed tomographs taken
      before treatment and immediately after HA insertion. Scans were registered on the
      cranial base and were analyzed using point-to-point measurements, color-coded
      maps, and semitransparent overlays. Statistical tests included correlation and
      simple regression analysis. Results: Pitch rotation, ranging from -2.2 degrees 
      to 2.2 degrees  (mean, 0.2 degrees ), was observed in clockwise and
      counterclockwise directions. Condylar sagittal displacement presented a positive
      correlation with OJ changes. Each millimeter of OJ correction resulted in an
      anterior condylar displacement of approximately 0.95 mm. Vertical condylar
      displacement correlated with OB changes and varied mostly between 2 mm and 4.5
      mm. Conclusion: Immediately after HA insertion, no significant clockwise
      mandibular rotation was observed. The condyles were displaced anteriorly and
      inferiorly. Condylar anterior displacement and OJ correction presented a ratio
      close to 1:1. The vertical displacement of the condyles did not follow the same
      magnitude of OB changes.

PMID- 30112472
TI  - A Patient- and Family-Centered Care Approach to Orthodontics: Assessment of
      Feedbacks from Orthodontic Patients and Their Families.
AB  - Objective: This study aimed to evaluate orthodontic patients and their families'
      clinical satisfaction and their perception of dentists in the framework of the
      Patient and Family Centered Care (PFCC) concept. Methods: The study population
      comprised patients treated at the Orthodontics clinic and their families. A mixed
      method research with quantitative and qualitative components was employed by
      conducting questionnaires with 62 patients and 65 parents. Collected data were
      recorded on the computer, and analyses were performed. Results: A majority of the
      patients who received treatment at our clinic were high school graduates, while
      their parents were university graduates. The patient's and their parents' overall
      satisfaction were similar. We also found that the patients and their parents
      expected doctors to have ethical perception and professional behavior in the
      treatment process. Conclusion: According to the results obtained from the survey
      questionnaires, the patients and their parents expect a dentist to have the
      following qualities: courtesy, friendliness, respect, punctuality, communication
      skills, and knowledgeableness. Dentists can optimize clinical and patient
      satisfaction by providing care and attention based on the principles of patient
      centered care (PCC) and PFCC and shaped in accordance with the expectations of
      the patients and their parents.

PMID- 30112473
TI  - Evaluation of Patients with Cleft Lip and Palate in Southeastern Anatolian
      Region.
AB  - Objective: Our study included patients with cleft lip and palate who applied to
      Gaziantep University Dentistry Faculty Orthodontics Department between 2010 and
      2014. The aim of this study was to reveal the characteristics of these patients
      with demographic values. Methods: In total, 118 patients were included in this
      study. The patients were pursued by phone calls, and the study was conducted with
      only 64 patients. The demographic map was created with a statistical expert as a
      questionnaire. Results: It was thought that the reason for not being able to
      include the remaining 54 patients was a change in phone number, designation, or
      others. One patient who was to be interviewed died because of heart failure. The
      results revealed that the place of birth of 18.75% patients was a metropolitan
      region that of 54.68% was a province, that of 21.87% was a district, and that of
      4.69% was a village. The majority of patients (93.25%) had a low family income
      level. The average number of children was 3.28, and readership was 1.47. The rate
      of working mothers was 1.56%. Conclusion: It was concluded that the cleft lip and
      palate patient group had lower economic and sociocultural levels. For this
      purpose, raising awareness of parents and providing financial support to families
      are required because of the long-term treatment process. It was thought that the
      long-term treatment process of these patients in a single-unit authority with the
      guidance of universities would be appropriate for better patient follow-up and
      inventory. Otherwise, as seen in this study, contact cannot be established after
      a while and some problems can arise with regard to follow-up. Lack of
      communication can lead to the formation of more difficult patients with growth
      and development.

PMID- 30112474
TI  - Which Orthodontic Wire and Working Sequence Should be Preferred for Alignment
      Phase? A Review.
AB  - The key to a successful orthodontic therapy depends not only on manual skills and
      knowledge about treatment steps, but also on knowledge and choice of materials
      used. One of the major components of fixed orthodontic therapy is the choice of
      wires. Orthodontic wires are defined as devices consisting of a wire conforming
      to the alveolar or dental arch, used as an anchorage in correcting irregularities
      in the position of the teeth. The history of these materials is as old as that of
      fixed orthodontic treatments and they present different features. With proper
      general knowledge, doctors can differentiate between wires and use the sufficient
      wire sequence suitable for each patient. This can increase the quality of
      treatment. Therefore, the aim of the present review is to focus on the
      differences in features of wires as well as the sequence of leveling wire
      selection according to the treatment plan.

PMID- 30112475
TI  - Survey on Retention Protocols Among Turkish Orthodontists.
AB  - Objective: The purpose of this study was to identify general retention protocols
      practiced by Turkish orthodontist and to compare the results obtained with those
      of similar studies in Western countries. Methods: The Web-based survey consisted
      of 29 questions: 3 to identify the demographic characteristics of the
      participants and 26 to examine how orthodontists manage the retention phase. Data
      was interpreted by descriptive statistical methods such as the median test, the
      Mann-Whitney U-test and logistic regression analysis. Results: The survey return
      rate was 73.8%. Pretreatment malocclusion status (87%), oral hygiene status
      (78%), and presence of third molars (63%) were reported to be the most important
      factors in determining the type of retainer. Bonded retainers, either alone (29%
      in maxilla and 34% in mandible) or supplemented with vacuum-formed retainers (27%
      in maxilla and 32% in mandible) were the most commonly used type of retainer. The
      preference for lifelong retention varied from 7% to 19%. Female orthodontists
      scheduled the first appointment after debonding sooner than male orthodontists
      (p<0.05). Orthodontists working in universities scheduled first appointments
      later than orthodontists working in private practices (p<0.05). Conclusion:
      Turkish orthodontists still give importance to the third molars in their
      retention protocols, contrary to what is suggested in the current literature, and
      lifetime retention is rarely preferred as compared to other countries.

PMID- 30112476
TI  - Perception of Smile Esthetics by Orthodontists and Laypersons: Full Face and A
      Localized View of The Social and Spontaneous Smiles.
AB  - Objective: The aim of the study was to evaluate the parameters that might affect
      the esthetic perception of localized and full-face views of social and
      spontaneous smiles. Methods: Video records of 40 individuals were used. Further,
      200 images of each individual were captured for social and spontaneous smiles
      with and without calibration glasses. Full-face images of social smile (SSF) and
      spontaneous smile (smile of joy) (JSF) were obtained. Furthermore, the mouth-area
      images of the same social (SSM) and spontaneous (JSM) smiles from each subject
      were acquired. Here 160 images were evaluated by orthodontists and laypersons
      using the Q-sort method. The data were analyzed with logistic regression and
      independent samples t-test. Results: From the orthodontic perspective, upper lip
      thickness (p=0.004), lip curtain over incisors (p=0.016), maxillary incisor
      display (p=0.01), and buccal corridor ratio (p=0.006) were significant to
      determine attractive and unattractive images when viewing localized social
      smiles. Laypersons identified no particular parameter to explain the variation in
      preferences for all the image groups (p>0.05). Conclusion: Upper lip thickness
      and maxillary incisor display during smiling were found to be effective for
      distinguishing images as attractive and unattractive by orthodontists. No
      objective evaluations for the attractiveness were made by laypersons.

PMID- 30112477
TI  - The Role of Blood Spot Dehydroepiandrosterone Sulfate Levels in Adjunct to Hand
      Wrist Radiographs as Skeletal Maturity Indicator.
AB  - Objective: The purpose of this study was to find out whether blood spot
      Dehydroepiandrosterone Sulfate (DHEAs) levels can be used as Skeletal Maturity
      Indicators (SMI) by correlating them to hand-wrist maturation stages. Methods:
      The cross sectional study population consisted of 107 subjects (62 females and 45
      males) 5-25 years old. Hand-wrist radiographs were obtained, and the subjects
      were divided into 5 groups based on the hand-wrist skeletal maturity stages. A
      blood spot sample was collected and immunoassayed for DHEAs. Analysis of variance
      was used to compare the mean DHEAs levels corresponding to the hand-wrist
      maturation stages. Pearson's correlations were performed to determine the DHEAs
      trends relating to the various hand-wrist maturation stages. Results: DHEAs
      levels increased continuously from the prepubertal stage to the acceleration,
      high growth velocity/peak, deceleration, and postpubertal stages (r=0.17), but
      the total increase was not found to be statistically significant (p=0.08).
      Conclusion: The blood spot DHEAs level cannot be used as an SMI in individuals.
      Nevertheless, it can be used in conjunction with hand wrist radiographs to
      predict and validate the skeletal maturation. The role of DHEAs in the
      termination of growth and residual growth may be a subject for further research.

PMID- 30112478
TI  - Applications of Cone Beam Computed Tomography in Orthodontics: A Review.
AB  - Cone Beam Computed Tomography (CBCT) is being extensively used in orthodontics
      for diagnostic and treatment planning, especially in complex clinical conditions.
      The objective of this study was to review the English language literature for
      current applications and trends of CBCT in orthodontic diagnosis and treatment.
      Several electronic databases were searched with the primary words: "orthodontics
      and radiography" and "cone beam computed tomography" or "CBCT." Abstracts that
      appeared to fulfill our inclusion criteria were selected, and the complete
      articles were obtained. Twenty-eight abstracts initially met our search criteria,
      and 12 were selected for the review. Ten articles were later added to the list
      after hand searching the references. It was concluded that there is a need for
      prospective randomized clinical trials to evaluate the risk/benefit ratio of
      CBCT, such as higher cost, greater risk for radiation dose (compared to digital
      panoramic and cephalograms) versus superior diagnosis and treatment outcomes.

PMID- 30112480
TI  - Influence of Lateral Cephalometric Radiography on Treatment Planning and
      Preferences in Skeletal Open-Bite Patients: Do Lateral Cephalograms Influence
      Treatment Planning?
AB  - Objective: To investigate the influence of diagnostic data derived from lateral
      cephalometric radiographs (LCR) on treatment preferences of specialists planning
      skeletal open-bite treatment. Methods: Diagnostic records of 25 patients who had
      been treated at the University of Zurich, Department of Orthodontics, between
      1988 and 2007 comprised the study material. Inclusion criteria were 1) skeletal
      open-bite with no marked antero-posterior discrepancy, 2) dental open-bite, and
      3) crowding less than 5 mm. Records consisted of extra-intraoral photographs,
      panoramic-cephalometric X-rays, casts, and results of analyses. Records, with
      cephalograms of randomly chosen patients removed, were digitally presented to two
      orthodontists (A and B), and treatment preferences were asked using Likert-type
      questionnaires. Three months later, the same records were redelivered with
      missing cephalograms provided and present cephalograms removed with the
      questionnaire. Data were evaluated for consistency and tendency to extract using
      Kappa-kappa and McNemar tests. Results: Orthodontist B had no poor-agreement
      scores, whereas orthodontist A presented very-poor agreement for headgear use.
      Both A (kappa=0.833) and B (kappa=0.737) had good to very-good agreement in terms
      of extraction decisions. Neither orthodontist had any significant tendency for
      extraction/non-extraction therapy (A=0.99; B=0.5). Conclusion: Information
      deduced from LCRs had limited influence on treatment planning preferences in
      skeletal/dental open-bite patients with no marked antero-posterior discrepancy
      and no influence on extraction/non-extraction decision.

PMID- 30112479
TI  - Indirect Bonding Revisited.
AB  - In recent years, the popularity of indirect bonding increased due to advantages
      such as reduction of chair time and enhancement of patient comfort. Although the
      indirect bonding technique has improved over the years, the literature has shown
      different techniques of bracket placement; furthermore, new materials were
      specially developed for this technique. The aim of this article is to provide a
      review of the literature, advantages, disadvantages, and laboratory and clinical
      stages of the indirect bonding technique.

PMID- 30112481
TI  - Evaluation of the Relationship between Curve of Spee, WALA-FA Distance and Curve
      of Wilson in Normal Occlusion.
AB  - Objective: To test the hypotheses that (i) there is a significant correlation
      between the curve of Spee (COS), basal arch (WALA ridge) to dental arch distance
      (WALA-FA distance) and curve of Wilson (CW) and that (ii) the deepening of the
      COS is affected by the CW and the WALA-FA distance. Methods: Mandibular models of
      50 patients aged between 20 and 35 years were scanned with TRIOS. The xyz
      coordinate system was determined, and a reference occlusal plane was generated.
      The depth of the COS, the CW, and WALA-FA distance were measured using an
      engineering software. Results: The greatest difference in the measurement of the
      depth of the COS between the right and left was found to be 0.41+/-0.50 mm in the
      first molar teeth. On the basis of the results of Pearson correlation analysis,
      there was no strong correlation between the depth of the COS, the CW, and the
      WALA-FA distance. Conclusion: It was shown that there was no strong correlation
      between the depth of COS, CW, and WALA-FA distance. The CW and WALA-FA distance
      could not be effective in the deepening of the COS.

PMID- 30112482
TI  - Reliability Assessment of Orthodontic Apps for Cephalometrics.
AB  - Objective: The aim of this study was to evaluate the accuracy and reliability of
      cephalometric measurements using iPad apps called CephNinja and SmartCeph Pro.
      The measurements were compared with the measurements obtained using Dolphin
      Imaging computer software. Methods: Twenty digital cephalometric radiographs were
      randomly selected from the archives and traced using the CephNinja app, SmartCeph
      Pro app, and Dolphin Imaging software. Twenty-one landmarks and 16 measurements
      were performed in each program. The statistical analysis was conducted using the
      Bland-Altman analysis at a significance level of 0.05. Results: For the CephNinja
      app, there were seven measurements that were in accordance with Dolphin Imaging
      software. For the SmartCeph Pro app, six measurements were in accordance with
      Dolphin software. Both apps gave better results for angular measurements than
      linear ones. Conclusion: These findings indicate that, although they are user
      friendly, orthodontic apps for cephalometrics are not equal with Dolphin software
      now and need to be developed to be more reliable for most of the measurements.

PMID- 30112483
TI  - Root Resorption in Orthodontics.
AB  - Root resorption has been the subject of many studies, and it can be caused by
      many factors such as the mechanics used during orthodontic treatment, factors
      related to the type and magnitude of the force, and other factors related to
      treatment such as the type of tooth movement and malocclusion. The clinical
      importance of root resorption is directly related to its detectability.
      Therefore, orthodontic and biological factors that may cause root resorption were
      evaluated using various imaging methods in present use. In this review, root
      resorption in orthodontics was considered from different viewpoints.

PMID- 30112484
TI  - Various Contemporary Intraoral Anchorage Mechanics Supported with Temporary
      Anchorage Devices.
AB  - The aim of this review was to provide an overview of the various types of
      contemporary intaroral anchorage mechanics that are being used with temporary
      anchorage devices (TADs) and to briefly mention the design and clinical use of
      these appliances. Original articles on "mini-implants in orthodontics, temporary
      anchorage devices, orthodontic miniscrews, mini-implants, and skeletal anchorage"
      were searched for on the PubMed database. Articles published between 2004 and May
      2015 were used. References of 10 articles were also searched for and used.
      Beneslider, Miniscrew-supported EZ slider, Implant-supported Distal Jet, Mini
      implant-Borne Pendulum B Appliance, Noncompliance-supported Maxillary Molar
      Distalization Appliance, Temporary Skeletal Anchorage Device-Supported Rapid
      Maxillary Expansion Appliance (RME), Mini-Implant-Supported Maxillary Expansion,
      Implant-Supported RME, Hybrid Hyrax, Frog Appliance, Palatally Anchored
      Mesialslider, Mousetrap Appliance, Lever Arm, and Mini-implant System were
      evaluated. In contemporary orthodontics, TADs have an important place. They can
      be combined with different intraoral mechanics and be efficiently used. The
      future of orthodontic intraoral anchorage may be based on TADs.

PMID- 30112485
TI  - Level of Social Appearance Anxiety in Individuals with and without Alignment of
      Teeth.
AB  - Objective: The aim of this study is to determine the level of social appearance
      anxiety in individuals with and without alignment of teeth and to demonstrate
      that orthodontic treatment is effective in reintegrating the individual into
      society, as well as in improving self-confidence communication skills, and self
      esteem. Methods: The present study included 50 patients (24 males and 26 females)
      with dental alignment and 50 patients (28 males and 22 females) without dental
      alignment. The study was performed as an interview study using the Social
      Appearance Anxiety Scale, which measures emotional, cognitive, and behavioral
      anxiety felt by the individual due to his/her appearance. Hypotheses were proven
      by t-test and one-way analysis of variance using the Statistical Package for the
      Social Sciences program. Results: The mean level of social appearance anxiety was
      higher in patients with dental misalignment (p<0.05). The result of t-test
      analysis revealed no significant difference between the scores of male and female
      participants (p>0.05). Conclusion: The level of social appearance anxiety
      increases in individuals with dental misalignment. However, it is independent
      from gender.

PMID- 30112486
TI  - Evaluation of Skeletal and Dental Effects of Modified Jasper Jumper Appliance and
      Delaire Face Mask with Pancherz Analysis.
AB  - Objective: The aim of this study was to evaluate the skeletal and dental changes
      in Class III patients treated with Modified Jasper Jumper appliance and Delaire
      face mask before the growth peak. Methods: A study sample comprising 16 patients
      with functional Class III malocclusion treated with Modified Jasper Jumper
      appliance and 17 patients treated with Delaire face mask was compared with a
      control group comprising 13 patients. Pancherz analysis was used as the analysis
      method. Results: In both treatment groups forward movement of maxillary base and
      incisors and an increase in the overjet while no positional change in the
      mandibular base was observed. In the Modified Jasper Jumper group, 4.63 mm
      overjet correction was due to 51.4% skeletal and 48.6% dental changes; 4.77 mm
      Class III molar correction was due to 49.9% skeletal and 50.1% dental changes. In
      the Delaire face mask group, 5.17 mm overjet correction was due to 70.6% skeletal
      and 29.4% dental changes and 4.87 mm Class III molar correction was due to 75%
      skeletal and 25% dental changes. Conclusion: It was shown that both appliances
      were skeletally and dentally effective. Therefore, Modified Jasper Jumper therapy
      may be an alternative treatment modality for patients with poor cooperation, who
      are not ideal recipients for Delaire face mask.

PMID- 30112487
TI  - Effect of Bionator and Farmand Appliance on the Treatment of Mandibular
      Deficiency in Prepubertal Stage.
AB  - Objective: The present study aimed to compare dentoskeletal changes in mandibular
      deficient patients treated with Bionator and Farmand appliances. Methods: This
      study included 54 subjects treated for class II division I malocclusion. All
      subjects fulfilled the following criteria: ANB>5 degrees , SNB<77 degrees , and
      overjet >5 mm. The Bionator group consisted of 27 patients (15 girls, 12 boys)
      with the mean age of 11 (SD 1) years and the Farmand group consisted of 27
      patients (17 girls, 10 boys) with the mean age of 11.1 (SD 1.4) years.
      Statistical analyses were performed using t-test, paired t-test, Wilcoxon, and
      Mann-Whitney test. Results: In the Farmand group, SNB significantly increased
      from 74.3 degrees  (SD 1.7) to 77.6 degrees  (SD 2.3) and ANB decreased by 3.2
      degrees  (SD 1.7) (p<0.001). In the Bionator group, SNB significantly increased
      from 75.5 degrees  (SD 0.9) to 79 degrees  (SD 0.9), and ANB decreased by 3.3
      degrees  (SD 1.3) (p<0.001). The increase in IMPA showed that the lower incisors
      were significantly tipped using both appliances. T-test did not show any
      significant differences between the two groups. Conclusion: Despite the different
      designs of the appliances, both were successful in the treatment of class II
      division 1 malocclusion in mandibular-deficient patients.

PMID- 30112489
TI  - Extraction Orthodontic Treatment in an Autistic Patient.
AB  - Autism is a condition that restricts brain development. Early diagnostic criteria
      are as follows: less responsive to social stimuli, inability to develop natural
      speaking skills, lack of communication skills, and limited and repetitive
      behaviors. Orthodontic treatment is a challenging process for doctors in autistic
      patients. The clinical and cephalometric examination of a 17-year and 7-month-old
      autistic patient revealed class I malocclusion, increased vertical dimensions,
      proclined upper and lower incisors, and inconsistent lip closure. The treatment
      plan involved four premolar extractions from each quadrant. Upper and lower 1.
      premolar extraction with fixed treatment caused reduction in vertical dimensions
      and significant improvement in lip closure and incisor inclination. Due to the
      increased metabolic activity in these patients, treatment was completed in 13
      months. As a result, autistic patients can be successfully treated. In this
      process, it is important to include communication as a major part of treatment.

PMID- 30112488
TI  - The Factors Affecting Long-Term Stability in Anterior Open-Bite Correction - A
      Systematic Review.
AB  - Objective: The present systemic review was conducted with the main purpose to
      evaluate the quantitative effects of orthognathic surgeries, extraction versus
      non-extraction treatment, and the type of malocclusion in the stability of
      anterior open-bite (AOB) correction over the long-term. Methods: The systematic
      search for studies was conducted through MEDLINE, CINAHL, EMBASE, Scopus,
      PsychINFO, various key journals, and review articles; November 30, 2016, was the
      last date for the search. The Quality Assessment Tool for Quantitative Studies
      was used to grade the methodological quality of the studies. Results: The present
      review included 14 studies. Stability of the corrected AOB ranged from 61.9% to
      100%. The studies with orthognathic surgeries showed a stability of 70-100%. The
      studies without orthognathic surgeries showed the stability of 61.9-96.7%. All of
      the studies were retrospective. The mean change in AOB before (T1) and after
      treatment (T2-T1) was 0.1 mm to 6.93 mm and the mean change in overbite from T2
      to T3 (T3-T2) was -0.06 mm to 2.5 mm. Conclusion: Studies with orthognathic
      surgeries presented with high amount of long-term stability in corrected AOB. No
      significant difference was noticed in relation to the type of malocclusion and
      extraction or non-extraction cases.

PMID- 30112490
TI  - Patients' and Parents' Perception of Functional Appliances: A Survey Study.
AB  - Objective: To evaluate patients' and parents' perception of removable, fixed
      rigid, and fixed hybrid functional appliances and to compare their impacts on
      anxiety and discomfort during treatment in different age groups and genders.
      Methods: Data were gathered by means of a questionnaire that included items
      presumed to be associated with orthodontic compliance. A self-administered
      questionnaire was used to quantify patients' and parents' perceptions. Three
      groups were formed regarding the type of functional appliance used: fixed rigid
      (Functional Mandibular Advancer, FMA), fixed hybrid (Forsus Fatigue Resistant
      Device, FRD), and removable (Twin Block, TB). Two separate questionnaires were
      used for the patients and their parents comprising the necessary context. Chi
      square, Mann-Whitney U, and Kruskal-Wallis tests were used for data analysis.
      Results: Patients needed less time to adapt to the FRD appliance. Eating
      difficulties were encountered by patients in the FMA group. Adolescents who had
      completed functional orthodontic treatment with a removable appliance had
      difficulties in controlling their saliva. Patients' and parents' perceptions were
      found to be in accordance with each other. Conclusion: Adolescents who had
      completed functional orthodontic treatment with fixed appliances had more
      difficulty in their daily life. Orthodontists should be aware of this impact
      caused by functional orthodontic treatment and should regularly encourage
      patients by reminding them of the improvements to be had by fixing the
      malocclusion.

PMID- 30112491
TI  - Dental Arch Dimensions of Nigerian Children with Hypertrophied Adenoids.
AB  - Objective: The study objective was to assess the effect of adenoid hypertrophy on
      the dental arch dimensions of children in Ile-Ife, Nigeria. Methods: Ninety
      patients aged 3-12 years attending the Otorhinolaryngology Clinic at Obafemi
      Awolowo University Teaching Hospital Ile-Ife diagnosed as having hypertrophied
      adenoids and 90 children from the Child Dental Health Clinic were recruited as
      adenoid and control subjects respectively. Arch and palatal vault dimensions,
      including total arch length; inter-canine, inter-premolar, and inter-molar
      widths; palatal length; and palatal heights measured at three levels and palatal
      volume were determined for both groups from dental casts. Results: Maxillary arch
      dimensions were shorter in the adenoid group than the control group; however,
      only total maxillary arch length was significantly shorter (p=0.049). Mandibular
      arch dimensions with the exception of inter-molar width were significantly
      shorter in the adenoid group (p<0.05). Adenoid subjects had significantly
      increased palatal heights at canine, premolar, and molar levels and reduced
      palatal volume compared to the control subjects (p<0.05). Conclusion: Adenoid
      subjects demonstrated shorter maxillary and mandibular arch dimensions compared
      with control subjects, with the differences being more evident in the lower arch.
      They also exhibited increased palatal heights at all levels and reduced palatal
      volume compared with control subjects.

PMID- 30112492
TI  - Smile Attractiveness: Differences among the Perceptions of Dental Professionals
      and Laypersons.
AB  - Objective: The aim of this study was to analyze the acceptable values of female
      and male smile attractiveness based on different amounts of gingival display and
      buccal corridor widths, as judged by dental professionals and laypersons.
      Methods: The frontal smile photographs of a male and female model were modified
      to create seven different smile photographs of the same individual with different
      amounts of gingival display and buccal corridor widths. Overall, 249 evaluators
      in four groups (Group 1=orthodontists, Group 2=prosthodontists, Group 3=oral
      surgeons, and Group 4=laypersons) evaluated 28 images of different smiles with a
      visual analogue scale. Significant statistical differences were found among the
      evaluator's scores (p<0.05). Results: For female smiles, the highest scores were
      obtained for 12% and 0% buccal corridor width. For male smiles, the highest
      scores were obtained for 4%, 0%, 12%, and 16% buccal corridor width for Groups 1,
      2, 3, and 4 respectively. The highest scores were obtained for +2 mm and -3 mm of
      gingival display for female smiles. Conclusion: The amount of gingival display,
      the buccal corridor width, and the knowledge in the field affects the perceptions
      of smile attractiveness. Thus, 3 mm of gingival display and buccal corridor width
      larger than 16% should be avoided for esthetic reasons during dental treatment.

PMID- 30112493
TI  - Treatment of Midline Deviation with Miniscrews: A Case Report.
AB  - A 15-year-old female presented with the chief complaint of crowding. Extraoral
      examination revealed little facial asymmetry, which was related with mandibular
      deviation caused by constriction of the maxilla. Upon intraoral examination,
      Class III molar and Class II canine relationships were seen on the right side,
      and Class III molar and Class III canine relationships were seen on the left
      side. A morphological lower midline shift was detected (4 mm to the right). After
      the start of treatment with rapid maxillary expansion, miniscrews were inserted
      into the buccal shelf and canine-premolar areas in order to solve the
      morphological deviation without extractions. Because there was a need to shift
      the lower midline to the right side, miniscrews were inserted into the left
      buccal shelf at the right canine-premolar area. The miniscrews were placed
      vertically so that the angle between the long axes of the teeth and the long axes
      of the screws were approximately 20 degrees. Acceptable correction of the midline
      deviation lasted for four months. At the end of the treatment, a good occlusal
      relationship was obtained.

PMID- 30112494
TI  - Treatment of a Class II Case with Palatally Inserted Distalization Mechanics in
      an Epilepsy Patient.
AB  - This case report describes the protocol employed in the treatment of a patient
      with Class II malocclusion with mechanics including palatally positioned
      miniscrews. Treatment included the distalization of maxillary posterior teeth
      with mechanics including 2 miniscrews positioned on the palatal side. After a
      certain amount of distalization was achieved, the maxillary arch was bonded with
      Roth prescription brackets while the appliance was still active. When leveling of
      the upper arch was finished, the appliance was kept in the mouth as a retention
      device while the mandibular arch was bonded to continue treatment, which lasted
      for a total of 15.5 months. Mandibular and maxillary fixed retainers were placed
      at the end of active treatment. Pretreatment and post-treatment records revealed
      that vertical and sagittal skeletal cephalometric findings were not affected.
      Miniscrew anchorage used during distalization is an effective non-extraction
      treatment option for dental Class II malocclusion correction.

PMID- 30112495
TI  - Impact of Orthognathic Correction of Class II Malocclusion on the Perception of
      Social Characteristics.
AB  - Objective: To evaluate the influence on the perception of social characteristics
      after orthognathic treatment for the correction of Class II malocclusion.
      Methods: A cross-sectional study was conducted with the participation of 240
      observers who evaluated images of individuals before and after orthognathic
      surgery for the correction of malocclusion. Based on the images, two different
      questionnaires were applied containing 44 questions each for evaluating social
      competence, intellectual ability, psychological adjustment, and attractiveness.
      The mean scores for evaluations of the images were compared using the Mann
      Whitney U test at 5% level of significance (alpha=0.05). Results: Orthognathic
      treatment significantly (p<0.05) improved the evaluation of individuals in the
      requisites of the score attributed to the image (p=0.008), extroversion
      (p=0.026), happiness (p=0.006), self-confidence (p=0.046), and attractiveness
      (p=0.015). Conclusion: Orthognathic treatment for the correction of Class II
      malocclusions has a positive effect on the perception of social characteristics
      of individuals. The individuals subjected to orthognathic surgery were evaluated
      as being more attractive, intelligent, socially competent, and psychologically
      adjusted.

PMID- 30112496
TI  - Prevalence of Need of Orthodontic Treatment in 7-16-Year-Old School Children in
      Udaipur City, India.
AB  - Objective: The study aimed to estimate the need of orthodontic treatment in 7-16
      year-old school children in Udaipur city, India. Methods: This cross sectional
      study enrolled 1029 subjects (661 males and 368 females) belonging to Udaipur
      city, Rajasthan, India. Subjects who had not undergone orthodontic treatment were
      randomly selected. The need for orthodontic treatment was assessed using the
      Dental Health Component of the Index of Orthodontic Treatment Need (IOTN) by the
      same calibrated examiner. Collected data were quantitatively analyzed, and the
      difference pertaining to prevalence between males and females was measured using
      the chi-square test. Results: A Grade 1 IOTN score was observed in 48.4% of the
      population. Grade 2 was observed in 22.9% of the population. A significant
      difference was noted for the prevalence of Grades 1, 2, and 3 between male and
      female children, with male children showing greater prevalence of malocclusion
      grades. Grades 4 and 5, which were noted less frequently, did not show a
      significant difference with respect to sex. Conclusion: A higher percentage of
      the sample required moderate orthodontic treatment. This necessitates proper
      education and motivation to undergo orthodontic treatment.

PMID- 30112497
TI  - Information on the Internet Regarding Orthognathic Surgery in Turkey: Is It an
      Adequate Guide for Potential Patients?
AB  - Objective: To evaluate the quality of information on websites regarding
      orthognathic surgery in Turkey using the DISCERN toolkit. Methods: An Internet
      search was performed using the Google search engine with the terms "orthognathic
      surgery", "jaw surgery", "jaw operation", "correcting jaw surgery", and "surgery
      orthodontics." The first 25 websites obtained after searching for each term were
      evaluated. Duplicate websites, advertisements, discussion groups, links to
      research articles, videos, and images were not considered. The remaining websites
      were analyzed using the DISCERN toolkit. This toolkit is composed of 15 questions
      that were scored from 1 to 5. Results were calculated as mean scores,
      percentages, and ranges. Results: Among the 36 evaluated websites, 12 (33.3%)
      belonged to plastic surgeons, 11 (30.6%) belonged to orthodontists, 8 (22.2%)
      belonged to private dental clinics, 3 (8.3%) belonged to maxillofacial surgeons,
      1 (2.8%) was a professional organization website, and 1 (2.8%) belonged to a
      private hospital. The Turkish Orthodontic Society had the only listed
      professional organization website. The mean total DISCERN score was 28/75 (range:
      15-48). The overall quality of information in 44.4% of the websites was low. The
      main problems of websites were as follows: no mention of the aims, sources, and
      production time of information; no links for additional sources of information;
      and no information for patient carers. Conclusion: The quality of web-based
      information on orthognathic surgery was generally low. Higher quality information
      provided by public organizations that do not have profit concerns is required.

PMID- 30112498
TI  - Treatment of Class II, Division 2 Malocclusion with Miniscrew Supported En-Masse
      Retraction: Is Deepbite Really an Obstacle for Extraction Treatment?
AB  - A 17-year-old female patient, whose chief complaint was her unpleasing smile, had
      skeletal and dental class II malocclusion, hypodivergent facial type with a
      severely increased overbite. Among the treatment options, upper-first-premolar
      extractions followed by miniscrew-supported en-masse retraction was the treatment
      of choice. After the initial levelling and alignment, miniscrews with 1.5- to 1.4
      mm diameter and 7-mm lenght, were installed between the roots of the second
      premolars and the first molars, bilaterally. En-masse retraction was achieved on
      a 0.016*0.022-inch stainless steel archwire with 7-mm long power hooks placed
      distal to the lateral incisors, and with nickel-titanium (NiTi) closed coil
      springs exerting 250-gr of force per side. At the end of the treatment, deepbite,
      incisor inclinations and interincisal angle were corrected, and Class II molar
      relationship with good intercuspation was achieved. Upper 2-2, lower 3-3
      retainers were bonded for retention. As a result, deepbite and Class II canine
      relationship was successfully corrected with simultaneous incisor intrusion and
      retraction using miniscrew-supported en-masse retraction.

PMID- 30112499
TI  - Treatment of a Class II Patient with Four Premolar Extractions and Driftodontics
      in the Lower Jaw.
AB  - The clinical examination of an 11.10-year-old girl in permanent dentition showed
      severe crowding, chewing problems and her right maxillary lateral incisor was in
      palatal position. The molars were in Class II relationship on both sides. An
      extraction treatment was planned. Upper second premolars and lower first
      premolars were extracted. Lower crowding was eliminated using physiological tooth
      movement called "driftodontics". Slots sized 0.022 inches and self-ligating
      brackets were used. The patient also used a high-pull headgear for anchorage and
      vertical control reasons for a short period. During the correction of the lateral
      crossbite, a posterior bite plate was used for anterior disarticulation and
      anterior bite ramps were used at the last stages of the treatment to ease the
      correction of the curve of Spee. Class I molar and canine relationships and
      normal overjet and overbite achieved with good alignment of both arches and
      dental midlines coincided with the facial midline. The treatment results were
      stable after 2 years of the retention period.

PMID- 30112500
TI  - Effects of Ozone and Prophylactic Antimicrobial Applications on Shear Bond
      Strength of Orthodontic Brackets.
AB  - Objective: The present study aimed to evaluate the effects of ozone and
      prophylactic antimicrobial applications on the shear bond strengths and bond
      failure interfaces of orthodontic brackets. Methods: Sixty human canine teeth
      were randomly divided into three groups (n=20), receiving the following
      treatments: Group I-pumice prophylaxis (Isler Dental, Ankara, Turkey)+37%
      orthophosphoric acid (Dentsply, Rio de Janeiro, Brazil)+Transbond XT primer and
      adhesive (3M Unitek, Monrovia, USA); Group II-prophylaxis paste (Topex, NJ,
      USA)+37% orthophosphoric acid (Dentsply, Rio de Janeiro, Brazil)+ Transbond XT
      primer and adhesive paste (3M Unitek, Monrovia, USA); and Group III-ozone
      application (Biozonix GmbH, Munich, Germany)+37% orthophosphoric acid (Dentsply,
      Rio de Janeiro, Brazil)+Transbond XT primer and adhesive (3M Unitek, Monrovia,
      USA). All specimens were stored at 37 degrees C water for 24 h. Shear bond
      strength was assessed using a universal testing device (Autograph AGS-X;
      Shimadzu, Japan). Adhesive remnant index (ARI) scores were obtained through
      examination of teeth under stereomicroscope at 10* magnification after debonding.
      Results: Shear bond strengths of orthodontic brackets were 16.10, 18.01, and
      19.23 MPa for Groups I, II, and III, respectively. No statistically significant
      difference in shear bond strength of orthodontic brackets was found among the
      groups (p=0.273), based on Kruskal-Wallis analysis. Additionally, no significant
      difference was found in the ARI scores of each group using chi-square analysis
      (p=0.992). Conclusion: Shear bond strength of orthodontic brackets and ARI scores
      was not found to be negatively impacted by ozone application.

PMID- 30112501
TI  - Effects of the Vertical Malocclusion Types on the Dimension of the Mandibular
      Condyle.
AB  - Objective: This study aimed to find the relationship between mandibular condyle
      morphology and dental malocclusion in patients with anterior open bite, deep
      bite, and normal overbite. Methods: Eighty patients were included in this
      retrospective study. All patients had skeletal Class II pattern. The initial
      panoramic radiographs of patients were digitized using a software program, and
      groups were compared in terms of condylar height, width, area, and perimeter. In
      addition, changes in the condyle surface shape were detected using the same
      panoramic radiographs. Results: The mean width was 1.55+/-0.06 cm in the open
      bite group, 1.48+/-0.06 cm in the deep bite group, and 1.38+/-0.07 cm in the
      normal bite group. The mean height was 2.17+/-0.08 cm in the open bite group,
      1.95+/-0.06 cm in the deep bite group, and 1.97+/-0.08 cm in the normal bite
      group. The mean area was 2.33+/-0.13 cm2 in the open bite group, 2.09+/-0.11 cm2
      in the deep bite group, and 2.04+/-0.14 cm2 in the normal bite group. There was
      no statistical significant difference between groups in terms of condyle
      measurements and condyle surface shapes. Conclusion: The results suggest that the
      vertical malocclusion type does not have a considerable effect on the mandibular
      condyle measurements and surface shapes.

PMID- 30112502
TI  - Postoperative Positional and Dimensional Changes of Mandibular Canal after
      Bilateral Sagittal Split Set-Back Osteotomy.
AB  - Objective: This preliminary study was planned to provide information about
      preoperative mandibular canal (MC) position and the postoperative positional
      changes of MC and length in three dimensions, with the purpose of providing some
      assistance in reducing inferior alveolar neurosensory disturbance (IAND).
      Methods: MC was examined on CBCT data using SimPlant Pro Standalone 13.0. MC
      locations were measured in all dimensions, with respect to mandibular bony
      borders. Results: The results showed that MC is frequently located in the
      midthird of the ramus anteroposteriorly and superoinferiorly and in the midthird
      of the corpus superoinferiorly. Postoperatively, ramus width was increased, ramus
      length was decreased significantly, and MC was repositioned laterally and
      inferiorly. MC length was decreased on both sides, non-correlated with the set
      back amounts. Conclusion: Preoperative results may be beneficial for the
      prediction of MC position for surgeons, and postoperative results will be used
      for the following studies to correlate postoperative positional changes with
      IAND.

PMID- 30112503
TI  - Presurgical Nasoalveolar Molding of Bilateral Cleft Lip and Palate Infants: An
      Orthodontist's Point of View.
AB  - Nonsyndromic complete cleft lip and palate deformity is primarily functional,
      then esthetic, and finally but not least importantly, a dental challenge. Feeding
      and facial appearance are important during the first years of a newborn.
      Nutrition is universally provided by passive feeding plates. If the Cleft Team
      prefers to use active plates, alveolar molding combined with nasal approaches in
      infants is the best method to improve esthetics to date. Orthodontists are
      predominantly responsible for achieving both the goals. After those difficulties
      have been met in early days of the life, dentists are mainly responsible for the
      treatment thereafter. If the infants have a dentoalveolar unity without any
      fistulas and correctly aligned maxillary deciduous teeth, this is a real success.
      Therefore, this article is an overview of presurgical infant orthopedics and its
      contribution to subsequent dental practice.

PMID- 30112505
TI  - 30th Volume Index.

PMID- 30112504
TI  - Camouflage Treatment of a Severe Deep-Bite and Orthognathic Surgery Required Case
      with En Masse Retraction.
AB  - In adult patients with severe class II division 2 malocclusion, the ideal
      treatment option is the orthognathic surgery. However, camouflage therapy is also
      an acceptable treatment option due to its less traumatic and acceptable esthetic
      and functional results. In this case report, the camouflage treatment with two
      maxillary premolar extractions in a 21-year-old female patient who did not accept
      orthognathic surgery is presented. Acceptable esthetic and functional results
      were obtained at the end of the treatment.

PMID- 30112506
TI  - Combined Use of Retraction and Torque Arch with Mini-Screws: A Cephalometric
      Study.
AB  - Objective: Our objective was to investigate and quantify the treatment of micro
      implant-aided retraction and torque (R&T) arch on dentofacial structures.
      Methods: Twelve patients (mean age 21.2 years) who required orthodontic
      camouflage treatment were included in the study. Following the canine
      distalization, mini-screws were placed between maxillary first molars and second
      premolars, and R&T arch was applied for the retraction of incisors. The vertical
      retraction arms of the arch were adjusted between the apex of the lateral incisor
      and the alveolar bone so that the retraction force passed through the center of
      resistance of four incisors and forced the incisors to bodily retraction. Closed
      coil-springs applying 150 gr of force were used to retract the incisors. The
      retraction period lasted for 217+/-34 days. Results: SNA and NV-A decreased
      (p<0.05), indicating alveolar bone remodeling around Point A. The reduction in
      the SNA caused a statistically significant decrease in the ANB (p<0.01). SN/1,
      NA/1, NA-1, and overjet decreased significantly (p<0.01), depending on the
      retrusion of the incisors. The distances from the apex and incisal point of the
      central incisor to the SV reference plane also decreased significantly (p<0.01),
      revealing a nearly parallel movement of the incisors. Anchorage loss of the
      molars and decrease in nasolabial angle were not significant (p>0.05).
      Conclusion: A combined use of R&T arch with mini-screws is an effective method to
      retract the incisors without anchorage loss. The type of movement is nearly
      parallel.

PMID- 30112507
TI  - Dentofacial Effects of Fixed Functional Appliances with or without Mini Screw
      Anchorage in the Treatment of Class II Division I Malocclusion: A Finite Element
      Analysis.
AB  - Objective: This study aimed to examine the biomechanical effects of the fixed
      functional appliances reinforced with miniscrews by finite elements analysis over
      the cranial and facial bones, temporomandibular joint, and maxillary-mandibular
      teeth, which are used for the treatment of Class II division 1 malocclusions
      characterized as mandibular retrognathia. Methods: Three-dimensional (3-D) models
      of the cranial, mandibular, and maxillary bones were purchased from a company
      that produces 3-D models of the bones. Simulations of Forsus, screwed Forsus,
      Twin-Force and screwed Twin-Force appliances were conducted on the 3 D models.
      The miniscrew was placed in the inter-radicular area between the upper canine and
      first upper premolar teeth. Results: It was observed in the models that the first
      upper molar tooth was the most affected. The compressive stress was observed in
      the anterior area of the mandibular condyle neck in the Forsus appliances;
      however, it was observed in the posterior area of the mandibular condyle neck in
      Twin-Force appliances. Conclusion: It was observed that molar distalization and
      expansion decreases in the functional appliances with the support of miniscrew.
      The highest tension rates were determined in the areas of condylar and articular
      discs.

PMID- 30112508
TI  - Assessment of Gingival Biotype and Keratinized Gingival Width of Maxillary
      Anterior Region in Individuals with Different Types of Malocclusion.
AB  - Objective: The aim of the present study is to evaluate the relationship of
      gingival thickness and width of keratinized gingiva with different malocclusion
      groups and amount of crowding. Methods: A total of 181 periodontally healthy
      subjects were enrolled in the present study. The study participants were divided
      into three malocclusion groups: Angle Class I, Angle Class II, and Angle Class
      III. Each group was divided into subgroups according to the amount of dental
      crowding, namely mild, moderate, and severe. The width of keratinized gingiva was
      calculated as the distance between mucogingival junction and free gingival
      margin, whereas gingival thickness was determined by a transgingival probing
      technique. Results: Tooth numbers 13 and 23 were observed to have thin gingival
      biotype. The width of keratinized gingiva for tooth numbers 13 and 23 was
      narrower in the severe crowding group than in the moderate and mild crowding
      groups. The relationship of gingival thickness and width of keratinized gingiva
      with Angle classification was not found to be significant. Conclusion: Although
      it is thought that there is a relationship between gingival thickness, width of
      keratinized gingiva, and Angle classification with regard to malaligned teeth,
      this cross-sectional evaluation of 181 patients failed to show a significant
      relationship.

PMID- 30112510
TI  - Intraoral Molar Distalization with Intraosseous Mini Screw.
AB  - The aim of the present study was to evaluate the effects of the miniscrew
      supported, modified Hyrax appliance on bilateral distalization of posterior
      teeth. A 15-year-old girl with Class II malocclusion (end-to-end molar
      relationships, space deficiency for maxillary canine) underwent orthodontic
      treatment. The patient rejected tooth extraction. Then, she was treated with the
      miniscrew-supported, modified Hyrax appliance. An activation of 1 mm per month
      was planned. Lateral cephalometric views were used to evaluate distal movement.
      Distalization was successfully achieved at 4 months. No anchorage loss and
      incisor protrusion were noted. It would be beneficial to choose this appliance
      for the distalization of maxillary molars in patients with maxillary incisor
      protrusion, as this appliance does not cause anchorage loss in the upper jaw.

PMID- 30112511
TI  - Erratum.
AB  - [This corrects the article on p. 101 in vol. 30.].

PMID- 30112509
TI  - Microbial Colonization on Elastomeric Ligatures during Orthodontic Therapeutics:
      An Overview.
AB  - The current review focuses on the studies conducted on the colonization of
      microorganisms on orthodontic ligatures during orthodontic treatment. The fixed
      orthodontic appliances have long been associated with an increase in plaque
      accumulation, bacterial colonization, and resultant enamel decalcification.
      Voluminous research has been carried out on the microbial colonization of even
      newer orthodontic materials such as elastomeric ligatures with an evidence of
      variably increased microbial counts during orthodontic treatment. However,
      conclusive material-based data for minimal microbial colonization to establish
      acceptance criteria for the use of elastomeric ligatures are hardly available.
      Thus, there is a need for further studies with dual emphasis on exploring
      microbial associations based on surface chemistries of different elastomers and
      their requisite modifications for hampering microbial biofilms to evolve
      efficacious oral health friendly orthodontic ligatures.

PMID- 30112512
TI  - Upper Lip Asymmetry During Smiling: An Analysis Using Three-Dimensional Images.
AB  - Objective: The aim of this study was to use three-dimensional images to determine
      the presence of upper lip asymmetry at rest and during smiling in a group of
      individuals with no history of orthodontics or facial cosmetic surgery. Methods:
      Standardized three-dimensional frontal resting and smiling images of 54
      volunteers were analyzed using the 3dMDvultus software (3dMD, Atlanta, GA).
      Measurements were made from the soft tissue nasion, ipsilateral ala, subnasale,
      and menton to the right and left commissures of the lip. A 2.5 mm or greater
      difference between the right and left sides was defined as an asymmetry. The
      agreement on the presence or absence of asymmetry between the subjects' states of
      rest and smiling was determined by the McNemar's chi-squared test. Statistical
      significance was defined as p<0.05. Results: Menton was the most stable facial
      landmark to evaluate the upper lip symmetry at rest and during smiling (p=0.002).
      Using menton as a landmark, only one of the 54 subjects showed asymmetry while
      resting, but 12 (22%) showed asymmetry when smiling. Conclusion: As part of
      treatment planning for orthodontics or orthognathic surgery, patients should be
      evaluated for the upper lip symmetry during resting and smiling. The presence of
      asymmetry during smiling is a significant clinical problem that needs to be
      recognized so that patients can be informed about the effect it can have on the
      final esthetic result.

PMID- 30112513
TI  - Evaluation of the Compliance of Orthodontists to Infection Control Procedures in
      Turkey.
AB  - Objective: Orthodontists do not perform surgical procedures, nevertheless they
      are obliged to practice appropriate sterilization techniques to prevent cross
      infection. This is also important from an ethical and legal point of view. The
      aim of the present study is to evaluate the compliance of orthodontists to
      infection control procedures in Turkey. Methods: A questionnaire with 36 items
      was delivered by e-mail to a total of 1152 orthodontists/residents between
      October 2014 and March 2015 by the Turkish Orthodontic Society. Various data from
      surveys were analyzed using the IBM SPSS statistics 22 software. Results: The
      questionnaire was completed by 130 (11.28%) respondents. 95.4% of the
      orthodontists were immunized against hepatitis B. The usage rates of type B
      autoclave, non-type B autoclave, and dry-heat sterilizer were 40%, 17.7%, and
      16.9%, respectively. A total of 24.6% of the orthodontists used disinfectant
      solutions for the sterilization of hand instruments and pliers; the rate of using
      disinfectants for the sterilization of dental handpieces was found to be higher
      (56.9%). Conclusion: The infection control procedures in the field of
      orthodontics must be improved in Turkey. Training on compliance with the
      infection control principles should be included in education programs, and these
      programs should be repeated on a regular basis.

PMID- 30112514
TI  - Evaluation of Internet Information about Lingual Orthodontics Using DISCERN and
      JAMA Tools.
AB  - Objective: To investigate the quality and reliability of websites providing
      information about lingual orthodontics in Turkish. Methods: An internet search
      was conducted on March 6th, 2017, using popular search engines in Turkey:
      GoogleTM, bingTM, YAHOO!(r), and Yandex(r) for the keywords "lingual ortodonti,
      gorunmeyen braketler, and gorunmeyen teller". The top 10 websites for each
      keyword and search engine were examined, and duplicates, irrelevant websites,
      websites showing scientific articles, and orthodontic supplies market sites were
      excluded. The remaining 58 sites were assessed using the DISCERN instrument and
      JAMA benchmarks. Results: The authors of the remaining sites were orthodontists
      (48%) and dentists (5%), while 46% of the websites did not state author names.
      Ninety-one percent lacked references, and 87% lacked a date. Only 30% were
      balanced and unbiased. The mean overall DISCERN score was very poor (43%) or poor
      (40%). Of the 58 websites, 48% (28 sites) met authorship, 7% (4 sites)
      attribution, 71% (41 sites) disclosed website ownership, and 3% (2) currency
      benchmarks of JAMA. Conclusion: Information on the internet related to lingual
      orthodontics is poor. Clinicians should warn patients that information on the
      internet about lingual orthodontics might be inadequate, and they should direct
      patients to higher-quality websites.

PMID- 30112515
TI  - Cone Beam Computed Tomography in Orthodontics.
AB  - Orthodontists treat malocclusions by applying three-dimensional forces. For
      years, the diagnosis of this three-dimensional condition and the related
      treatment plan has been based on two-dimensional imaging. Lateral and
      anteroposterior cephalometric, panoramic, and periapical radiographs are some of
      the two-dimensional radiographs routinely used in orthodontics. Despite being
      highly beneficial in evaluating skeletal and dental relations, these radiographs
      fail to provide sufficient two-dimensional information in certain cases. The
      purpose of this compilation is to review the use of cone-beam computed tomography
      in orthodontics.

PMID- 30112516
TI  - Lingual Treatment of an Adult Patient with a Simplified Extraction Protocol.
AB  - Successful orthodontic treatment of adult cases depends on the biological,
      mechanical, and esthetic requirements of patients. While customized lingual
      appliance systems meet the esthetic expectations of the patients, they provide
      improved patient comfort, have three-dimensional mechanical control, and can be
      used for the treatment of all types of malocclusions. This report demonstrated
      the use of fully customized lingual orthodontic brackets for treating an adult
      case with extraction.

PMID- 30112517
TI  - The Challenges of Screening Mammography in Racial/Ethnic Minority Populations in
      the United States: A mini-review and observations from a predominantly Hispanic
      community.
AB  - Screening mammography is recommended by U.S. medical organizations for breast
      cancer screening in average risk women because of its demonstrated reductions in
      breast cancer mortality. However, significant disparities in breast cancer
      screening utilization and mortality remain among racial/ethnic minorities.
      Efforts have appropriately been directed at increasing engagement with screening
      services in these populations, however, there is a dearth of data regarding false
      positive rates and overdiagnosis in minority patients engaged in breast cancer
      screening. We recently examined screening practices among a predominantly
      Hispanic population presenting to an academic medical center in New York, NY, and
      found that approximately 53% of women experienced at least one false-positive
      mammography result over a median of 8.9 years of screening. We also observed that
      Hispanic women were more likely to screen annually than white women despite
      recommendations to screen less frequently. In this review, we briefly review the
      benefits and harms of screening mammography in average-risk women, namely, false
      positive results and breast cancer overdiagnosis, followed by a discussion of the
      disparities in breast cancer screening and mortality among racial/ethnic minority
      populations. We then present our own recent observations and propose that future
      interventions among Hispanic and other minority populations could include patient
      and provider-centered educational programs that focus on providing a balanced
      discussion of benefits and harms of screening mammography.

PMID- 30112518
TI  - The Association of Hispanic Ethnicity with Nonalcoholic Fatty Liver Disease in
      Polycystic Ovary Syndrome.
AB  - : Polycystic Ovary Syndrome (PCOS) affects 10-15% of reproductive age women and
      is a recognized risk factor for nonalcoholic fatty liver disease (NAFLD). The
      more severe form of NAFLD, known as nonalcoholic steatohepatitis (NASH), results
      in liver inflammation with or without fibrosis, and is now a leading cause of
      cirrhosis. Ethnic differences are apparent in NAFLD, with higher prevalence in
      Hispanics, although the role of Hispanic ethnicity on risk for NAFLD/NASH in
      women with PCOS is not known. OBJECTIVE: The aim of this study was to evaluate
      ethnic differences in the prevalence and risk of NAFLD/NASH in women with PCOS.
      STUDY DESIGN: Among PCOS women followed in a large academic medical center the
      association of Hispanic ethnicity with elevated biomarkers of NASH, including
      plasma cytokeratin 18 (CK18) M30 fragments and/or ALT levels (n=303), was
      assessed. Prevalence of hepatic steatosis by Controlled Attenuation Parameter
      (CAP) imaging was also evaluated in a subset of PCOS women (n=35). RESULTS: The
      median cohort age (n=303) was 28 years (IQR 8), and 15.5% (n=47) were Hispanic,
      the majority of whom reported white race (94%). Most Hispanic women had hepatic
      steatosis on imaging, which was markedly higher than in non-Hispanics (83% vs
      24%, p=0.005). Approximately 17% of PCOS women had elevated ALT or elevated CK18,
      which was more common in Hispanics than non-Hispanics, at 34% vs 14%,
      respectively, p=0.002. On univariate analysis, Hispanic ethnicity was associated
      with two-fold higher odds of NASH (OR 2.0, 95% CI 1.0-3.9, p=0.038), and the
      association persisted after adjustment for HOMA-IR and waist circumference (AOR
      3.1, 95% CI 1.1-8.9, p=0.034). CONCLUSION: NAFLD/NASH is an important condition
      to be considered by PCOS providers and Hispanic women with PCOS are a
      particularly high-risk group that may warrant routine screening.

PMID- 30112523
TI  - Adaptive reorientation of endothelial collectives in response to strain.
AB  - Mature epithelial monolayers share the ability to coherently respond to external
      mechanical stimuli. Tissue remodeling requires cell shape changes and coordinated
      movements. Human endothelia provide an exquisite example of such emerging
      collective activities. As part of their function in maintaining body homeostasis
      under variable hemodynamic loadings, endothelial ensembles must dynamically adapt
      to wall shear stress and cyclic deformation. While the alignment of several types
      of cells, including fibroblasts, osteoblasts and epithelial tissues, in response
      to various flow conditions or wall shear stress levels has been described in
      detail, less is known about collective endothelial remodeling under pure wall
      deformation. Here, using a custom-developed bioreactor, we exposed mature human
      endothelia to two distinct physiological levels of cyclic loading, generating
      overlapping gradients of strain. Endothelial cells remodeled depending on the
      level of imposed strain yielding local variations of cell density. In particular,
      a collective cell orientation orthogonal to the main direction of strain was
      observed at low levels of wall deformation, while cells reoriented parallel to
      the main direction of strain at high levels of wall deformation. The tissue
      adaptation depended on the establishment of mature adherens junctions, which were
      reinforced by the polarized recruitment of the adaptor protein vinculin. The
      pivotal role of cell-to-cell junctions was confirmed by the biochemical
      inhibition of vascular endothelial cadherin homotypic contacts, which impaired
      the collective remodeling. Together, our data establish wall deformation as an
      independent determinant of endothelial architecture with direct implications in
      vascular physiopathology.

PMID- 30112519
TI  - Protein Kinase C-epsilon in Membrane Delivery during Phagocytosis.
AB  - During phagocytosis, internal membranes are recruited to the site of pathogen
      binding and fuse with the plasma membrane, providing the membrane needed for
      pseudopod extension and target uptake. The mechanism by which vesicles destined
      for the phagosome are generated, targeted, and fuse is unknown. We established
      that Golgi-associated protein kinase C-epsilon (PKC-epsilon) is necessary for the
      addition of membrane during FcyR-mediated phagocytosis. PKC-epsilon is tethered
      to the Golgi through interactions between its' regulatory domain and the Golgi
      lipids PI4P and diacylglycerol; disruption of these interactions prevents PKC
      epsilon concentration at phagosomes and decreases phagocytosis. The accumulated
      evidence suggests that PKC-epsilon orchestrates vesicle formation at the Golgi by
      a mechanism requiring lipid binding but not enzymatic activity. This review
      discusses how PKC-epsilon might mediate vesicle formation at the level of budding
      and fission. Specifically, we discuss PKC-epsilon binding partners, the formation
      of lipid subdomains to generate membrane curvature, and PKC-epsilon mediated
      links to the actin and microtubule cytoskeleton to provide tension for vesicle
      fission. Assimilating information from several model systems, we propose a model
      for PKC-epsilon mediated vesicle formation for exocytosis during phagocytosis
      that may be applicable to other processes that require directed membrane delivery
      and fusion.

PMID- 30112524
TI  - Elucidation of the inverse trans influence in uranyl and its imido and carbene
      analogues via quantum chemical simulation.
AB  - The inverse trans influence (ITI) is investigated in uranyl, UO22+, and its
      isoelectronic imido (U(NH)22+) and carbene (U(CH2)22+) analogues at the density
      functional and complete active space self consistent field levels of theory. The
      quantum theory of atoms in molecules is employed to quantify, for the first time,
      the effect of the ITI on covalent bond character and its relationship to bond
      lengths and complex stability.

PMID- 30112525
TI  - A highly sensitive naked-eye fluorescent probe for trace hydrazine based on 'C
      CN' bond cleavage.
AB  - In this work, a colorimetric and ratiometric fluorescent probe, 2,3-bis(((E)-4
      (diethylamino)-2-hydroxybenzylidene)amino)maleonitrile (DHM), was developed based
      on N2H4-induced bond cleavage. Two cyanide groups of DHM were applied to sense
      hydrazine (N2H4) for the first time, which was demonstrated using 1H NMR and HRMS
      spectra. The specific 'C-CN' bond cleavage induced by N2H4 showed an excellent
      fluorescence ratiometric behavior and a visible colorimetric change from purple
      to yellow. Meanwhile, it showed a low detection limit of 58.1 nM (1.65 ppb),
      which is far below the safety level (10 ppb) set by the U.S. EPA. Moreover, the
      probe was successfully employed for the quantitative detection toward N2H4 in
      real water samples.

PMID- 30112527
TI  - Half-sandwich Os(ii) and Ru(ii) bathophenanthroline complexes: anticancer drug
      candidates with unusual potency and a cellular activity profile in highly
      invasive triple-negative breast cancer cells.
AB  - There is an urgent need to discover new, selective compounds to add to the
      limited arsenal of chemotherapeutics displaying selective toxicity for aggressive
      triple-negative breast cancer (TNBC) cells. The effect of two, recently developed
      metal-based half-sandwich complexes [Os(eta6-pcym)(bphen)(dca)]PF6 (Os-dca) and
      [Ru(eta6-pcym)(bphen)(dca)]PF6 (Ru-dca) [pcym = 1-methyl-4-(propan-2-yl)benzene
      (p-cymene); bphen = 4,7-diphenyl-1,10-phenanthroline (bathophenanthroline); dca =
      dichloroacetate] on triple-negative breast cancer cells MDA-MB-231 is reported.
      The complexes display selective toxicity in several tumor cells (at submicromolar
      concentrations), and a prominent effect is observed against highly progressive
      triple negative breast cancer MDA-MB-231 cells for Os-dca. The lower potency of
      Ru-dca in comparison with Os-dca is apparently connected with a relatively quick
      release of the dca ligand due to the hydrolysis of Ru-dca before this complex
      enters the cells. Remarkably, both Os-dca and Ru-dca reduce successfully
      metastasis-related properties of the triple-negative breast cancer cells such as
      migration, invasion, and re-adhesion. The anti-metastatic effects of Os-dca and
      Ru-dca are associated with their ability to suppress matrix metalloproteinase
      activity and/or production and reduce the expression of aquaporins. Further
      detailed mechanistic studies reveal that Os-dca reverses Warburg's effect and
      oncosis seems to be a prominent mode of cell death that predominates over
      apoptosis. As such, Os-dca can efficiently overcome the resistance of cancer
      cells to clinically-used apoptotic inducers cisplatin and carboplatin. The
      cytostatic and anti-metastatic properties of Os-dca in MDA-MB-231 provide a
      strong impetus for the development of new metal-based compounds to target hardly
      treatable human TNBC cells and displaying different modes of action compared to
      the antitumor metallodrugs in clinical use.

PMID- 30112528
TI  - The integration of experiment and computational modelling in heterogeneously
      catalysed ammonia synthesis over metal nitrides.
AB  - In this perspective we present recent experimental and computational progress in
      catalytic ammonia synthesis research on metal nitrides involving a combined
      approach. On this basis, it suggested that the consideration of nitrogen
      vacancies in the synthesis of ammonia can offer new low energy pathways that were
      previously unknown. We have shown that metal nitrides that are also known to have
      high activity for ammonia synthesis can readily form nitrogen vacancies on their
      surfaces. These vacancies adsorb dinitrogen much more strongly than the defect
      free surfaces and can efficiently activate the strong N-N triple bond. These
      fundamental studies suggest that heterogeneously catalysed ammonia synthesis over
      metal nitrides is strongly affected by bulk and surface defects and that further
      progress in the discovery of low temperature catalysts relies on more careful
      consideration of nitrogen vacancies. The potential occurrence of an associative
      pathway in the case of the Co3Mo3N catalytic system provides a possible link with
      enzymatic catalysis, which will be of importance in the design of heterogeneous
      catalytic systems operational under process conditions of reduced severity which
      are necessary for the development of localised facilities for the production of
      more sustainable "green" ammonia.

PMID- 30112529
TI  - Modulation of the mechanism of apoptosis in cancer cell lines by treatment with
      silica-based nanostructured materials functionalized with different metallodrugs.
AB  - The mesoporous silica-based material SBA-15 (Santa Barbara Amorphous-15) has been
      modified with the aminodiol ligand 3-[bis(2
      hydroxyethyl)amino]propyltriethoxysilane (PADOH) to give the corresponding
      material SBA-PADOH. Subsequent functionalization with a diorganotin(iv) compound,
      SnPh2Cl2 (1), and with two titanocene derivatives, TiCp2Cl2 ([Ti(eta5-C5H5)2Cl2]
      (2)) and TiCpCpPhNfCl2 ([Ti(eta5-C5H5)(eta5-C5H4CHPhNf)Cl2] (3) (Ph = C6H5; Nf =
      C10H7)), gave the materials SBA-PADO-SnPh2 (M1), SBA-PADO-TiCp2 (M2) and SBA-PADO
      TiCpCp* (M3), respectively. SBA-PADOH and M1-M3 have been characterized by
      various techniques such as FT-IR, XRD, XRF, solid-state NMR, nitrogen adsorption
      desorption isotherms, electrochemical methods, SEM and TEM, observing that the
      functionalization has mainly taken place inside the pores of the corresponding
      porous system. In addition, mechanistic aspects of the apoptosis triggered by the
      synthesized materials have been studied in vitro in tumour cell lines derived
      from three distinct types of cancer in order to elucidate their growth inhibition
      and interference with the expression of tumour necrosis factor alfa (TNF-alpha)
      and the first apoptosis signal receptor (Fas or tumour necrosis factor receptor
      6). It was observed that the antiproliferative and proapoptotic capacity of the
      materials depends on their functionalization with the different cytotoxic
      prodrugs (organotin or titanocene derivatives). The study shows that M1-M3
      influence the metabolic activity of the tumour cells and modulate the apoptotic
      pathways by different mechanisms, according to the active compound inside the
      material.

PMID- 30112530
TI  - A system to monitor statin-induced myopathy in individual engineered skeletal
      muscle myobundles.
AB  - Microphysiological tissue engineering models of human skeletal muscle
      (myobundles) provide a platform to investigate the mechanism of muscle diseases
      and to study the response to drugs and toxins in vitro. To examine the dynamic
      response to drugs, which often take several days to induce responses, we
      developed a system to monitor the contractile force of the same human skeletal
      muscle myobundles over time before and after treatment with drugs. Myobundles
      were formed in series with Ecoflex films (platinum-catalyzed silicones) with
      embedded microbeads. The displacement of the microbeads in Ecoflex exhibited a
      linear relation between muscle force production and Ecoflex film stretch. Forces
      measured with the microbeads embedded in Ecoflex agreed well with simultaneous
      measurements with a force transducer. Application of the Hill model for the
      myobundles showed that the Ecoflex affected the magnitude of the response, but
      not the kinetics. After continuous exposure to 100 nM cerivastatin, both active
      and passive forces were reduced relative to controls after 2-4 days. The decline
      in force was associated with a decline in the muscle myofiber organization. The
      inhibitory effect of cerivastatin was reduced when 0.1-1 mM mevalonate was added
      with cerivastatin. Although addition of co-enzyme Q10 with cerivastatin inhibited
      degradation of sarcomeric alpha-actinin (SAA) in myoblasts, the contractile force
      still declined, suggesting that statin-induced myopathy was related to mevalonate
      pathway but the addition of co-enzyme Q10 was insufficient to overcome the effect
      of statins on the mevalonate pathway. Thus, cerivastatin rapidly induces myopathy
      which can be reversds with mevalonate but not co-enzyme Q10.

PMID- 30112531
TI  - Pentavalent phosphorus as a unique phosphorus donor in POCl3 homodimer and POCl3
      H2O heterodimer: matrix isolation infrared spectroscopic and computational
      studies.
AB  - Phosphorus, an important element among the pnicogen group, opens up avenues for
      experimental and computational explorations of its interaction in a variety of
      compounds. Although experimental proof of trivalent phosphorus bonding is limited
      and is growing with time, phosphorus bonding with pentavalent phosphorus has been
      a long sought after interaction both computationally and experimentally. In the
      present work, for the first time, we have provided unambiguous experimental
      evidence for the pentavalent phosphorus bonding interaction by exploiting a
      phosphoryl chloride (POCl3) prototype under isolated conditions at low
      temperatures. The POCl3 dimer and higher aggregates can be set as a unique
      example possessing pentavalent phosphorus bonding with a competing halogen
      bonding interaction. The POCl3-H2O heterodimer is another interesting system,
      stabilized through multiple phosphorus and hydrogen bonded interactions. Using
      matrix isolation infrared spectroscopy, the POCl3 homodimer and POCl3-H2O
      heterodimer were characterized and the structures were elucidated by employing ab
      initio and DFT methods. The multifaceted interactions in the POCl3 paradigm were
      investigated by using Natural Bond Orbital, Energy Decomposition and
      Electrostatic Potential Mapping analyses.

PMID- 30112532
TI  - A simple capillary-based open microfluidic device for size on-demand high
      throughput droplet/bubble/microcapsule generation.
AB  - We report an easily-established capillary-based open microfluidic device (COMD)
      as a simple and robust method for size on-demand generation of monodisperse
      droplets of various fluidic materials with controllable volume. A device is set
      up in which a capillary is positioned with its tip close to a flat surface with a
      precise gap distance in a container. The continuous phase remains static in the
      container, and the dispersed phase is pumped through the capillary and forms
      droplets at the exit of the gap. Monodisperse droplets, bubbles and microcapsules
      of various fluids with diameters of 10-300 MUm (picoliter to nanoliter) and
      generation frequency of 1-1000 Hz are obtained by controlling the gap distance in
      the range of 5-500 MUm. The droplet formation is caused by capillarity-induced
      narrowing of the dispersed phase at the capillary exit, with droplet size being
      determined by the gap volume and fluid flow. We find that, at low flow rate,
      using the same COMD, the generated droplet size is constant, being determined by
      the gap size; however, at higher flow rate, droplet size increases with the flow
      rate. Droplet types can be managed by fluids and surface modification of the
      capillary and bottom surfaces. High throughput droplet generation is achieved by
      in-parallel integration of multiple capillaries in one device. Such a COMD is
      simple and easy-to-build without complex microfabrication requirements; however,
      it is highly robust, flexible and easy-to-operate for size on-demand droplet
      generation. It offers an opportunity for common laboratories to perform droplet
      based assays, and has high potential for high throughput industrial
      emulsification applications as well.

PMID- 30112533
TI  - Fast and non-destructive Raman spectroscopic determination of multi-walled carbon
      nanotube (MWCNT) contents in MWCNT/polydimethylsiloxane composites.
AB  - A versatile Raman spectroscopic method to determine the contents of carbon
      nanotubes (CNTs) in CNT/polydimethylsiloxane (PDMS) composites is demonstrated,
      and important issues directly related to the accuracy of the measurement have
      been investigated. Initially, Raman microscopic mappings over an area of 6.0 *
      6.0 mm2 were carried out on CNT/PDMS composites, which revealed the existence of
      the partial localization of CNTs on a microscopic scale. Therefore, a laser
      illumination scheme covering a large sample area of 28.3 mm2 was employed to
      acquire a sample spectrum representative of the whole CNT concentration. The peak
      area ratio between the CNT and PDMS peaks clearly varied with the CNT
      concentration, whereas the reproducibility of measurements was degraded for the
      composites containing more than 3.0 wt% CNTs because of the decreased Raman
      sampling volume arising from the absorption of laser radiation by the CNTs. The
      laser penetration depth was semi-quantitatively investigated by observing the
      spectra of thin-sliced samples collected by positioning a Teflon disk behind the
      sample, and Monte Carlo simulations were employed to examine the internal photon
      propagation as well as explain the experimental observation. In summary, the
      fundamental issues affecting the Raman measurement of the CNT containing polymer
      matrix have been clearly addressed, and the finding here will be a beneficial
      basis for successful Raman spectroscopic analysis of different CNT-containing
      composites.

PMID- 30112534
TI  - Nonmonotonic strain dependence of lattice thermal conductivity in monolayer SiC:
      a first-principles study.
AB  - An increasing number of two-dimensional (2D) materials have already been achieved
      experimentally or predicted theoretically, which have potential applications in
      nano- and opto-electronics. Various applications of electronic devices are
      closely related to their thermal transport properties. In this work, the strain
      dependence of phonon transport in monolayer SiC with a perfect planar hexagonal
      honeycomb structure is investigated by solving the linearized phonon Boltzmann
      equation. It is found that the room-temperature lattice thermal conductivity
      (kappaL) of monolayer SiC is two orders of magnitude lower than that of graphene.
      The low kappaL is due to small group velocities and short phonon lifetimes, which
      can also be explained by the polarized covalent bond due to large charge transfer
      from Si to C atoms. In a considered strain range, it is proved that the SiC
      monolayer is mechanically and dynamically stable. With increased tensile strain,
      the kappaL of the SiC monolayer shows an unusual nonmonotonic up-and-down
      behavior, which is due to the competition between the change of phonon group
      velocities and phonon lifetimes of low frequency phonon modes. At low strain
      values (<8%), the phonon lifetime enhancement induces the increased kappaL, while
      at high strain values (>8%) the reduction of group velocities as well as the
      decrease of the phonon lifetimes are the major mechanisms responsible for
      decreased kappaL. Our works further enrich the studies on the phonon transport
      properties of 2D materials with a perfect planar hexagonal honeycomb structure,
      and motivate further experimental studies.

PMID- 30112535
TI  - A pH-responsive nanoprobe for turn-on 19F-magnetic resonance imaging.
AB  - We successfully fabricated 19F magnetic resonance imaging (MRI) nanoprobes by
      partly replacing the 2-methylimidazolate of the metal organic framework (MOF)
      matrix ZIF-8, of which the strong 19F MRI signal displays an interesting pH
      dependence property, indicating its great potential as a 19F MRI contrast agent
      for stimuli-responsive imaging with high penetration depth and low background.

PMID- 30112536
TI  - The bismuth tetramer Bi4: the nu3 key to experimental observation.
AB  - The spectroscopic identification of Bi4 has been very elusive. Two constitutional
      Bi4 isomers of Td and C2v symmetry are investigated and each is found to be a
      local energetic minimum. The optimized geometries and vibrational frequencies of
      these two isomers are obtained at the CCSD(T)/cc-pVQZ-PP level of theory,
      utilizing the Stoll, Metz, and Dolg 60-electron effective core potential. The
      fundamental frequencies of the Td isomer are obtained at the same level of
      theory. The focal point analysis method, from a maximum basis set of cc-pV5Z-PP,
      and proceeding to a maximum correlation method of CCSDTQ, was employed to
      determine the dissociation energy of Bi4 (Td) into two Bi2 and the adiabatic
      energy difference between the C2v and Td isomers of Bi4. These quantities are
      predicted to be +65 kcal mol-1 and +39 kcal mol-1, respectively. Two electron
      vertical excitation energies between the Td and C2v electronic configurations are
      computed to be 156 kcal mol-1 for the Td isomer and 9 kcal mol-1 for the C2v
      isomer. The most probable approach to laboratory spectroscopic identification of
      Bi4 is via an infrared spectrum. The predicted fundamentals (cm-1) with harmonic
      IR intensities in parentheses (km mol-1) are 94(0), 123(0.23), and 167(0) for the
      Td isomer. The moderate IR intensity for the only allowed fundamental may explain
      why Bi4 has yet to be observed. Through natural bond orbital analysis, the C2v
      isomer of Bi4 was discovered to exhibit "long-bonding" between the furthest apart
      'wing' atoms. This long-bonding is postulated to be facilitated by the sigma
      bonding orbital between the 'spine' atoms of the C2v isomer.

PMID- 30112537
TI  - Entangled chain polymer liquids under continuous shear deformation: consequences
      of a microscopically anharmonic confining tube.
AB  - We generalize our non-classical theory for the shear rheology of entangled
      flexible polymer liquids to address the consequences of a deformation-modified
      anharmonic tube confinement field. Numerical results for stress-strain curves,
      orientational relaxation time, primitive path (PP) step orientational order
      parameter, dynamic tube diameter and transverse entropic barrier under
      nonequilibrium conditions are presented as a function of dimensionless shear
      rate, strain and degree of entanglement. Deformation-induced changes of the tube
      field have essentially no effect on rheology under fast deformations conditions
      corresponding to Rouse Weissenberg numbers WiR > 1 because of the dominance of PP
      chain stretch. However, the scaling behavior of the effective orientational
      relaxation time and rheological response at low deformation rates WiR < 1 are
      significantly modified, with the stress overshoot coordinates predicted to become
      shear rate and degree of entanglement dependent. Stress-assisted transverse
      activated barrier hopping as a new channel of orientational relaxation is found
      to be potentially important when WiR < 1. The dynamic tube diameter and
      transverse entropic barrier that confines chains in a tube are rich functions of
      strain, shear rate and degree of entanglement. Deformation can increase or
      decrease the tube diameter, and non-monotonic changes with strain are possible
      due to competing consequences of PP orientation, chain stretch and stress. The
      transverse barrier is relatively high for all strains below the stress overshoot,
      for weaker entanglement, and for WiR > 1, corresponding to a dynamically stable
      tube. But for high enough degrees of entanglement and WiR < 1, although the
      barrier still exists it can become very low.

PMID- 30112538
TI  - Unexpected behaviour in derivatives of Barluenga's reagent, Hal(Coll)2X (Coll =
      2,4,6-trimethyl pyridine, collidine; Hal = I, Br; X = PF6, ClO4 & BF4).
AB  - For the collidine analogues of Barluenga's Reagent (IPy2BF4) reported, a flat
      cation is necessary for the generation of a modulated phase, in keeping with the
      "Ratchet Model" theory [Kim et al., Crystal Growth & Design, 2014, 14, 6294].
      Attempts to study "diffuse modulation" in Br(Coll)2ClO4 have shown that these non
      Bragg features disappear very rapidly on exposure to synchrotron radiation, an
      effect thought to be caused by the radiation damage disrupting the lattice
      vibrations that cause the modulation.

PMID- 30112540
TI  - Absolute two-point quantification of proteins using dimethylated proteotypic
      peptides.
AB  - Absolute targeted proteomics typically employs known amounts of synthetic stable
      isotopically labeled peptides which are mixed with the analyte and analysed by LC
      MS to determine the concentration of proteins. In order to obtain more data, we
      evaluated the use of two different stable isotopes of the same peptide as spike
      in for absolute quantification. For this purpose, peptide labeling by reductive
      amination was applied, which is a mild reaction for dimethylation of amine groups
      with very high yield. Three different forms can be generated with e.g., light and
      heavy labels for spike-in peptides, and medium label for endogenous peptides. The
      method was studied with peptides of apolipoprotein A-I, apolipoprotein B-100, and
      leucine-rich alpha-2-glycoprotein without and with serum. In serum, the
      endogenous protein concentrations were measured across four orders of magnitude
      by the two-point quantification method. Less than 20% of coefficient of variation
      (CV) values and strong correlation with R2 of 0.99 across three analytical
      replicates was observed. Most importantly, the two-point quantification method
      allows an internal quality control of the spike-in peptide as strong deviations
      in ratios calculated between the first and second reference indicate a methodical
      error. Because of the significant lower costs than synthetically stable
      isotopically labeled peptides, this approach might be particularly interesting
      for the absolute quantification of multiple proteins.

PMID- 30112539
TI  - A supramolecular hydrogel prepared from a thymine-containing artificial
      nucleolipid: study of assembly and lyotropic mesophases.
AB  - An artificial nucleolipid containing thymine, a triazole-ring, and
      phosphatidylcholine (TTPC) moieties was prepared by copper catalyzed azide alkyne
      cycloaddition (CuAAC) under aqueous conditions. The resulting TTPC molecules
      assembled in situ into a fibrous aggregation. The study of the TTPC fiber
      assembly using XRD and NMR spectroscopy revealed that the formation of fibers was
      driven by the unique combination of the lipid and nucleobase moieties in the
      structure of TTPC. At a critical TTPC concentration, entanglement of the fibers
      resulted in the formation of a supramolecular hydrogel. Investigation of the
      lyotropic mesophases in the TTPC supramolecular hydrogel showed the presence of
      multiple phases including two liquid crystal phases (i.e., nematic and lamellar),
      which have a certain degree of structural order and are promising templates for
      constructing functional biomaterials.

PMID- 30112541
TI  - Probing magnetic interactions in metal-organic frameworks and coordination
      polymers microscopically.
AB  - Materials with magnetic interactions between their metal centres play a
      tremendous role in modern technologies and can exhibit unique physical phenomena.
      In recent years, magnetic metal-organic frameworks and coordination polymers have
      attracted significant attention because their unique structural flexibility
      enables them to exhibit multifunctional magnetic properties or unique magnetic
      states not found in the conventional magnetic materials, such as metal oxides.
      Techniques that enable the magnetic interactions in these materials to be probed
      at the atomic scale, long established to be key for developing other magnetic
      materials, are not well established for studying metal-organic frameworks and
      coordination polymers. This review focuses on studies where metal-organic
      frameworks and coordination polymers have been examined using such microscopic
      probes, with a particular focus on neutron scattering and density-functional
      theory, the most-well established experimental and computational techniques for
      understanding magnetic materials in detail. This paper builds on a brief
      introduction to these techniques to describe how such probes have been applied to
      a variety of magnetic materials starting with select historical examples before
      discussing multifunctional, low dimensional and frustrated magnets. This review
      highlights the information that can be obtained from such microscopic studies,
      including the strengths and limitations of these techniques. The article then
      concludes with a brief perspective on the future of this area.

PMID- 30112545
TI  - Theoretical discovery of novel two-dimensional VA-N binary compounds with
      auxiticity.
AB  - Auxetic materials, which possess a negative Poisson's ratio (NPR), have been a
      hot topic in materials science research. Through atomistic simulations, we
      theoretically rediscover a few novel two-dimensional (2D) VA-nitride (VA-N)
      binary compounds with delta-phosphorene-like structures. The structures in the
      delta-phase (except for delta-PN) exhibit better stability in terms of energy,
      thermodynamics, and mechanics with respect to their counterparts in the alpha-
      and beta-phases. The structures in the delta-phase show semiconducting behaviors
      with direct band gaps falling in the visible light region. Interestingly, most
      structures in the alpha- and delta-phases (except for delta-BiN) exhibit large in
      plane NPRs and excellent mechanical properties. The maximum NPR occurs along the
      zigzag (x) direction for the delta-phases and along the diagonal direction for
      the alpha-phases. Particularly, for alpha- and delta-SbN, the NPRs are -0.628 and
      -0.296, respectively. delta-SbN can sustain tensile strains of up to 22% and 35%
      with maximum stresses of 12.1 and 9.8 GPa in the zigzag and armchair directions,
      respectively. In addition, the transverse response can reach up to 6.6% at a
      strain of ~18% along the armchair (y) direction for delta-SbN, which is
      considerably higher than those of other 2D auxetic materials. Our results reveal
      that 2D VA-N binary compounds have potential applications in designing 2D
      electromechanical and optoelectronic devices.

PMID- 30112543
TI  - Automated microfluidic droplet sampling with integrated, mix-and-read
      immunoassays to resolve endocrine tissue secretion dynamics.
AB  - A fully automated droplet generation and analysis device based on pressure driven
      push-up valves for precise pumping of fluid and volumetric metering has been
      developed for high resolution hormone secretion sampling and measurement. The
      device consists of a 3D-printer templated reservoir for single cells or single
      tissue culturing, a Y-shaped channel for reagents and sample mixing, a T-junction
      channel for droplet formation, a reference channel to overcome drifts in
      fluorescence signal, and a long droplet storage channel allowing incubation for
      homogeneous immunoassays. The droplets were made by alternating peristaltic
      pumping of aqueous and oil phases. Device operation was automated, giving precise
      control over several droplet parameters such as size, oil spacing, and ratio of
      sample and reference droplets. By integrating an antibody-oligonucleotide based
      homogeneous immunoassay on-chip, high resolution temporal sampling into droplets
      was combined with separation-free quantification of insulin secretion from single
      islets of Langerhans using direct optical readout from the droplets. Quantitative
      assays of glucose-stimulated insulin secretion were demonstrated at 15 second
      temporal resolution while detecting as low as 10 amol per droplet, revealing fast
      insulin oscillations that mirror well-known intracellular calcium signals. This
      droplet sampling and direct optical analysis approach effectively digitizes the
      secretory time record from cells into droplets, and the system should be
      generalizable to a variety of cells and tissue types.

PMID- 30112546
TI  - Catalytic activations of unstrained C-C bond involving organometallic
      intermediates.
AB  - The cleavage of C-C bonds has been a great challenge owing to their thermodynamic
      and kinetic stability. To date, the progress made in this area has mainly relied
      on the reaction of small rings, which is driven by releasing ring strain.
      Encouragingly, more and more examples of the cleavage of non-strained C-C bonds
      have been reported. This review provides a comprehensive overview of the
      transition-metal-catalyzed C-C bond activation of relatively stable and
      unstrained molecules that involves the formation of organometallic intermediates.
      In the first section we focus on the C-C bond activation achieved through beta
      carbon elimination, and in the second section the oxidative addition of the C-C
      bond to low-valent metal is summarized in detail.

PMID- 30112549
TI  - Improving the activity of gold nanoparticles for the water-gas shift reaction
      using TiO2-Y2O3: an example of catalyst design.
AB  - In the last ten years, there has been an acceleration in the pace at which new
      catalysts for the water-gas shift reaction are designed and synthesized. Pt-based
      catalysts remain the best solution when only activity is considered. However,
      cost, operation temperature, and deactivation phenomena are important variables
      when these catalysts are scaled in industry. Here, a new catalyst, Au/TiO2-Y2O3,
      is presented as an alternative to the less selective Pt/oxide systems.
      Experimental and theoretical techniques are combined to design, synthesize,
      characterize and analyze the performance of this system. The mixed oxide
      demonstrates a synergistic effect, improving the activity of the catalyst not
      only at large-to-medium temperatures but also at low temperatures. This effect is
      related to the homogeneous dispersion of the vacancies that act both as
      nucleation centers for smaller and more active gold nanoparticles and as
      dissociation sites for water molecules. The calculated reaction path points to
      carboxyl formation as the rate-limiting step with an activation energy of 6.9
      kcal mol-1, which is in quantitative agreement with experimental measurements
      and, to the best of our knowledge, it is the lowest activation energy reported
      for the water-gas shift reaction. This discovery demonstrates the importance of
      combining experimental and theoretical techniques to model and understand
      catalytic processes and opens the door to new improvements to reduce the
      operating temperature and the deactivation of the catalyst.

PMID- 30112548
TI  - Conformational investigation of the structure-activity relationship of GdFFD and
      its analogues on an achatin-like neuropeptide receptor of Aplysia californica
      involved in the feeding circuit.
AB  - Proteins and peptides in nature are almost exclusively made from l-amino acids,
      and this is even more absolute in the metazoan. With the advent of modern
      bioanalytical techniques, however, previously unappreciated roles for d-amino
      acids in biological processes have been revealed. Over 30 d-amino acid containing
      peptides (DAACPs) have been discovered in animals where at least one l-residue
      has been isomerized to the d-form via an enzyme-catalyzed process. In Aplysia
      californica, GdFFD and GdYFD (the lower-case letter "d" indicates a d-amino acid
      residue) modulate the feeding behavior by activating the Aplysia achatin-like
      neuropeptide receptor (apALNR). However, little is known about how the three
      dimensional conformation of DAACPs influences activity at the receptor, and the
      role that d-residues play in these peptide conformations. Here, we use a
      combination of computational modeling, drift-tube ion-mobility mass spectrometry,
      and receptor activation assays to create a simple model that predicts
      bioactivities for a series of GdFFD analogs. Our results suggest that the active
      conformations of GdFFD and GdYFD are similar to their lowest energy conformations
      in solution. Our model helps connect the predicted structures of GdFFD analogs to
      their activities, and highlights a steric effect on peptide activity at position
      1 on the GdFFD receptor apALNR. Overall, these methods allow us to understand
      ligand-receptor interactions in the absence of high-resolution structural data.

PMID- 30112550
TI  - Correction: Water oxidation by a copper(ii) complex: new findings, questions,
      challenges and a new hypothesis.
AB  - Correction for 'Water oxidation by a copper(ii) complex: new findings, questions,
      challenges and a new hypothesis' by Mohammad Mahdi Najafpour et al., Dalton
      Trans., 2018, 47, 9021-9029.

PMID- 30112551
TI  - Lateral flow assays for Ochratoxin A using metal nanoparticles: comparison of
      "adsorption-desorption" approach to linkage inversion assembled nano-aptasensors
      (LIANA).
AB  - Nano-aptamer probes were prepared and used in lateral flow colorimetric assays
      for the detection of Ochratoxin A (OTA). In this study, two approaches were
      examined using 5'-biotin-modified OTA aptamers and silver or gold nanoparticles
      (AgNP or AuNP). The first method used an "adsorption-desorption" approach wherein
      aptamers were adsorbed onto the metal nanoparticle surface. Upon the addition of
      OTA, the aptamer binds specifically to the target, releasing the NPs. The above
      solutions were applied on a lateral flow assay (LFA) and a detection limit of 6.3
      nM was achieved with both metal nanoparticles. The second method used a labelled
      approach based on Linkage Inversion Assembled Nano-Aptasensors (LIANAs) using a
      DNA linker containing a 5'-5' linkage inversion (5'-5' linker) to assemble
      biotinylated aptamer-functionalized metal nanoparticles. In the presence of
      target, OTA specifically binds with its aptamer leading to release of the linker
      and disassembly of LIANA aggregates into dispersed nanoparticles. The same
      solutions were applied in LFA format and the lowest detection limit of 0.63 nM
      was achieved. The results indicated that the LIANA-based LFA strips were more
      sensitive than the "adsoprtion-desorption" LFAs. Both lateral flow assays are
      inexpensive, simple, and rapid to perform and produces results visible to the
      naked-eye.

PMID- 30112553
TI  - Lithium ions solvated in helium.
AB  - We report on a combined experimental and theoretical study of Li+ ions solvated
      by up to 50 He atoms. The experiments show clear enhanced abundances associated
      with HenLi+ clusters where n = 2, 6, 8, and 14. We find that classical methods,
      e.g. basin-hopping (BH), give results that qualitatively agree with quantum
      mechanical methods such as path integral Monte Carlo, diffusion Monte Carlo and
      quantum free energy, regarding both energies and the solvation structures that
      are formed. The theory identifies particularly stable structures for n = 4, 6 and
      8 which line up with some of the most abundant features in the experiments.

PMID- 30112557
TI  - Microliter viscometry using a bright-field microscope: eta-DDM.
AB  - The rheological properties of a medium can be inferred from the Brownian motion
      of colloidal tracer particles using the microrheology procedure. The tracer
      motion can be characterized by the mean-squared displacement (MSD). It can be
      calculated from the intermediate scattering function determined by Differential
      Dynamic Microscopy (DDM). Here we show that DDM together with the empirical Cox
      Merz rule is particularly suited to measure the steady-shear viscosity, i.e. the
      viscosity towards zero frequency, due to its ability to provide reliable
      information on long time and length scales and hence small frequencies. This
      method, eta-DDM, is tested and illustrated using three different systems:
      Newtonian fluids (glycerol-water mixtures), colloidal suspensions (protein
      samples) and a viscoelastic polymer solution (aqueous poly(ethylene oxide)
      solution). These tests show that common lab equipment, namely a bright-field
      optical microscope, can be used as a convenient and reliable microliter
      viscometer. Because eta-DDM requires much smaller sample volumes than classical
      rheometry, only a few microliters, it is particularly useful for biological and
      soft matter systems.

PMID- 30112558
TI  - In vitro and in vivo studies of a chlorin-based carbon nanocarrier with
      photodynamic therapy features.
AB  - Carbonaceous materials have long been developed to utilize "nano-spaces" and
      numerous guest species could be encapsulated. A remarkable fluorescence
      difference has been observed after newly designed pyropheophorbide-a-appended
      carbon nanohorns were incorporated in a cellular medium and confocal microscopy
      was employed for the determination of the intracellular localization. Our study
      supported the role of carbon nanohorns as carriers of photodynamic therapy (PDT)
      agents and their heating behavior was discussed. We have developed a theranostic
      platform based on photosensitizer-conjugated carbon nanostructures and this
      system has been applied in an animal model. In addition, a negligible toxicity of
      CNH-Pyro was found in body weight experiments and histopathological examination
      of the major organs.

PMID- 30112559
TI  - [Angiotensin II type 1 receptor autoantibody induces myocardial fibrosis by
      activating cardiac fibroblasts].
AB  - Myocardial fibrosis (MF) is an important pathological process of cardiac
      remodeling in patients with heart failure; however its etiology has not been
      clear. It has been known that the angiotensin II type 1 receptor autoantibody
      (AT1-AA) is present in patients with heart failure, but it is unclear whether
      this antibody directly causes MF. In this study, we investigated the role of AT1
      AA in MF and its effects on cardiac fibroblasts (CFs). The AT1-AA positive rat
      model was established by active immunization method, and the measurement of
      indexes were made in the 8th week after active immunity. The results of heart
      echocardiography showed that the cardiac systolic and diastolic functions of AT1
      AA positive rats were impaired with reduced left ventricular wall thickness and
      enlarged heart chambers. HE staining results showed that the myocardial fibers
      were disorganized and ruptured, and Masson staining revealed that the area of
      collagen fibers around the myocardium and coronary arteries was significantly
      increased in AT1-AA positive group compared with that of the control group (P <
      0.05). Moreover, primary CFs isolated from neonatal rats were cultured and
      treated with AT1-AA for 48 h. CCK-8 and immunofluorescence staining results
      showed that AT1-AA enhanced proliferation rate of CFs (P < 0.001), and Western
      blot results showed that AT1-AA significantly increased expressions of collagen I
      (Col I), Col III, matrix metalloproteinase-2 (MMP-2) and MMP-9 in CFs (all P <
      0.05). Taken together, these results suggest that AT1-AA may induce MF and
      cardiac dysfunction via activating CFs.

PMID- 30112560
TI  - [Bosentan ameliorates hypertension in rats exposed to chronic intermittent
      hypoxia through inhibiting renal sympathetic nerve activity].
AB  - The purpose of this study is to investigate the effect of the oral endothelin
      antagonist Bosentan on blood pressure and renal sympathetic nerve activity (RSNA)
      in rats exposed to chronic intermittent hypoxia (CIH), and to explore the
      sympathoexcitation mechanism of endothelin-1 (ET-1) in CIH-induced hypertension.
      Twenty-four male SD rats were randomly divided into normoxia, CIH and Bosentan
      groups. Rats in the normoxia group were exposed to normoxic environment, and rats
      in CIH or Bosentan group were exposed to intermittent hypoxia for 3 weeks.
      Bosentan was given at 50 mg/kg by intragastric administration before intermittent
      hypoxia exposure in Bosentan group. Systolic blood pressure (SBP) was measured by
      BP-2000, and the change of RSNA to sodium nitroprusside (SNP) or phenylephrine
      (PE) was recorded by PowerLab signal acquisition system. Serums of all rats were
      collected and the contents of ET-1 and norepinephrine (NE) were measured by
      ELISA. Results showed that blood pressure was gradually increased following CIH
      exposure compared with the normoxia group during the 3 weeks (P < 0.01, P < 0.01,
      P < 0.001). The basal RSNA was increased and baroreflex sensitivity was decreased
      in rats exposed to CIH. Furthermore, the blood pressure was positively correlated
      with the level of ET-1 in serum in rats exposed to CIH (r = 0.833, P = 0.01).
      Bosentan administration significantly decreased SBP and basal RSNA, increased the
      baroreflex sensitivity, and decreased serum NE level in rats exposed to CIH.
      These results suggest that ET-1 is related with blood pressure elevation in rats
      exposed to CIH, and Bosentan reverses CIH-induced hypertension by decreasing
      RSNA.

PMID- 30112561
TI  - [Bioinformatics analysis of genes related to pathogenesis of major depression
      disorder].
AB  - The aim of this study was to screen the genes related to the pathogenesis of
      major depression disorder (MDD) by bioinformatics. Taking GSE98793 chip data from
      GEO public database of National Biotechnology Information Center (NCBI) website
      as the research object, 116 differentially expressed genes (DEGs) were screened
      by R language limma package. Among the 116 DEGs, 66 genes were up-regulated and
      50 down-regulated. The results of gene functional annotation analysis of Gene
      Ontology (GO) showed that the DEGs were mainly distributed in mitochondria intima
      and mitochondria. They were involved in copper ion binding, cysteine-type
      endopeptidase activity, the cell response of interleukin-1, protein processing
      and other biological processes. KEGG pathway enrichment analysis results showed
      that the DEGs were mainly concentrated in oxidative phosphorylation, Parkinson's
      disease, non-alcoholic fatty liver disease, Alzheimer's disease and Huntington's
      disease etc. The results of protein interaction network analysis showed that
      there were interactions among proteins encoded by 54 DEGs. Combined with the
      analysis results of the above methods, 11 key genes were screened out, including
      UQCRC1, GZMB, NDUFB9, NSF, SLC17A5, CTSH, NDUFB10, UQCR10, ATOX1, CST7 and CTSW,
      which could be used as candidate genes for the diagnosis and treatment of MDD.
      Taken together, the key genes were obtained by analyzing the microarray and the
      DEGs of MDD in the present study, which would provide important clues for
      revealing the molecular mechanism and clinical targeted therapy of depression.

PMID- 30112562
TI  - [Clustering of vestibular direction-selective neurons in macaque parieto-insular
      vestibular cortex].
AB  - Neurons with direction-selectivity for vestibular stimuli are found in a number
      of cortical areas, and neurons in the ventral intraparietal area (VIP) and the
      dorsal subdivision of the medial superior temporal area (MSTd) of the macaque
      brain are clustered according to their direction preferences for vestibular
      signals. This raises the question where the clustering inherits from? Previous
      work has shown that VIP and MSTd most probably receive vestibular input from the
      parieto-insular vestibular cortex (PIVC), which processes vestibular signals at
      the earlier stage. Thus, PIVC is also supposed to show a clustered organization
      similar to that seen in VIP and MSTd. The present study was aimed to examine
      clustering properties of vestibular response in PIVC area. To address this issue,
      we compared the tuning of isolated single unit (SU) with the undifferentiated
      multiunit (MU) activity of several neighboring neurons recorded from the same
      microelectrode. When directional tuning was observed in MU activity, the
      direction preference generally agreed closely with that of a simultaneously
      recorded SU. These results suggest that PIVC neurons are indeed clustered
      according to preferred direction for both translational and rotational vestibular
      stimuli.

PMID- 30112563
TI  - [Differentially expressed circular RNAs in human gastric cancer cells].
AB  - The purpose of this study was to investigate the expression profile of circular
      RNA (circRNA) in gastric cancer cells MGC-803, SGC-7901 and NCI-N87 with
      different degrees of differentiation and normal gastric epithelial cells GES-1.
      High throughput circRNA microarray technique was used to detect the differential
      expression of circRNA between three kinds of differentiated gastric cancer cells
      and normal gastric epithelial cells. The interaction of microRNAs (miRNAs) with
      circRNAs was predicted by bioinformatics software, and circRNA, which might have
      great significance in gastric cancer, was identified by literature search. The
      results showed that there were 79 up-regulated circRNAs and 229 down-regulated
      circRNAs in gastric cancer cells with different degrees of differentiation
      compared with those in normal gastric epithelial cells. Through bioinformatics
      software analysis and literature retrieval, it was found that hsa_circ_0001897
      was related to the staging and metastasis of gastric cancer, while the miR-150
      5p, which combined with it, was closely related to many kinds of digestive tract
      tumors, such as colon cancer, liver cancer, and cholangiocarcinoma. The miR-16
      5p, which has binding sites with hsa_circ_0008106 and hsa_circ_0060456, has been
      confirmed to be involved in the development of gastric cancer. The above results
      suggest that hsa_circ_0001897, hsa_circ_0008106 and hsa_circ_0060456 may be
      closely related to the occurrence and development of gastric cancer by
      interacting with miRNA.

PMID- 30112564
TI  - [Sophoridine inhibits the proliferation of human gastric cancer MKN45 cells and
      promotes apoptosis].
AB  - The purpose of the study was to investigate the effect of sophoridine on the
      proliferation and apoptosis of human gastric cancer MKN45 cells and the possible
      mechanism. MKN45 cells were randomly divided into control and sophoridine
      (including 6 subgroups) groups. Cell proliferation was detected by methyl
      thiazolyl tetrazolium (MTT) colorimetric method. The protein expression of high
      mobility group-box 3 (HMGB3) was observed by immunocytochemical staining and
      Western blot. Hoechst 33342 staining method was used to observe the morphological
      changes of cells treated with sophoridine. Apoptosis was detected by flow
      cytometry. The results showed that the proliferation of cells was inhibited by 48
      hour treatment of sophoridine in a dose-dependent manner. Compared with control
      group, sophoridine group showed decreased HMGB3 protein expression and increased
      apoptotic rate. These results suggest that sophoridine can inhibit the
      proliferation of MKN45 cells and promote their apoptosis, which may be related to
      down-regulation of HMGB3 protein expression.

PMID- 30112565
TI  - [Wogonoside reverses cisplatin resistance in SGC7901/cDDP cells through
      inhibition of PI3K/Akt/Nrf2/ARE signaling pathway].
AB  - The aim of this study was to investigate the effect of wogonoside (WGS) on the
      cisplatin (cDDP) resistance in human gastric carcinoma SGC7901/cDDP cells and its
      possible mechanism. The drug-resistant SGC7901/cDDP cells were established by
      stepwise exposure to cDDP. CCK-8 assay was employed to detect the cytotoxic
      effect of WGS and cDDP on SGC7901/cDDP cells, and the combined effect of WGS and
      cDDP was analyzed by Chou-Talalay method. Flow cytometry was used to determine
      the apoptosis and reactive oxygen species (ROS). Nuclear factor erythroid-2
      related factor 2 (Nrf2) gene was knocked down by using the short hairpin RNA
      (shRNA) approach. The protein levels of Nrf2, NAD(P)H:quinone oxidoreductase 1
      (NQO1), glutathione S transferase-pi (GST-pi), multidrug resistance-associated
      protein 1 (MRP1), cleaved Capase-3, p-Akt and Akt were detected by Western
      blotting. The result showed that after various concentrations of WGS and/or cDDP
      treatment for 48 h, the cell viability was remarkably reduced in a dose-dependent
      manner (P < 0.05). When the inhibition rate exceeded 16%, the combination of WGS
      and cDDP produced a synergistic effect. The protein levels of p-Akt, Nrf2 and
      MRP1 in SGC7901/cDDP cells were higher than those in SGC7901 cells (P < 0.05).
      WGS and LY294002 (PI3K inhibitor) both remarkably decreased the phosphorylation
      level of Akt (P < 0.05), down-regulated the protein level of Nrf2 (P < 0.05),
      increased the content of ROS (P < 0.05), up-regulated the protein level of
      cleaved Caspase-3 (P < 0.05), and induced apoptosis (P < 0.05). Meanwhile, N
      acetyl-L-cysteine (NAC) decreased apoptosis and oxidative stress reaction induced
      by WGS (P < 0.05). WGS and Nrf2 gene silencing both down-regulated the protein
      levels of NQO1, GST-pi and MRP1 (P < 0.05). These results suggest that WGS may
      reverse cDDP resistance in SGC7901/cDDP cells through blocking the
      PI3K/Akt/Nrf2/ARE signaling pathway, thus enhancing the cytotoxicity of cDDP and
      inducing oxidative stress reaction and apoptosis.

PMID- 30112566
TI  - [Primary culture and identification of mouse renal proximal tubular epithelial
      cells].
AB  - The present study was aimed to establish a modified method for culturing mouse
      renal proximal tubular epithelial cells (TECs). Renal cortex was isolated from
      mouse kidney and scissored into pieces. TECs were separated by digesting
      scissored renal cortex in type II collagenase combined with strainer filtration,
      and then cultured in DMEM. The morphology of TECs was observed under inverted
      microscopy. The cell proliferative ability was assessed by flow cytometry, and
      cell viability was analyzed by CCK-8 assay. The purity of TECs was identified by
      immunofluorescence. Immunofluorescence observation showed that more than 95%
      cells were epithelial marker CK18 positive and more than 90% cells expressed
      renal proximal TECs marker proteins, Villin, AQP1, and SGLT2. The cells could be
      subcultured for about 5 times. The cell proliferative ability declined following
      the repeated passage. This study introduced a modified efficient method for
      culturing highly purified mouse renal proximal TECs.

PMID- 30112567
TI  - [Progress on ionomics of complex diseases].
AB  - Ionomics is a new multidisciplinary scientific field for investigating the
      composition and distribution of all chemical elements in specific biological
      systems as well as their variations under different physiological and
      pathological conditions. It combines both high-throughput techniques for element
      profile measurement and bioinformatic methods, which provides new ideas for
      obtaining a systems-level understanding of biological utilization and functions
      of these elements. More and more results of researches suggest that ionomics has
      important theoretical and practical values in etiological study, early diagnosis
      and screening, and therapeutic strategy selection for complex diseases. In this
      review, we focus on current advances in the ionomic studies of several complex
      diseases, which may help further understand the effect and important properties
      of individual elements, as well as their dynamic ionomic networks in the
      occurrence and development of diseases.

PMID- 30112568
TI  - [Research progress of mitochondrial fission and fusion related proteins].
AB  - Mitochondria are an essential component of multicellular life and play important
      roles in the health of the cells and the body. Mitochondria can produce energy by
      oxidative phosphorylation, mediate calcium and reactive oxygen signal
      transduction, and regulate cell apoptosis. Recent studies indicate that
      mitochondria continually change their shapes and distribution by fission and
      fusion, which are collectively termed mitochondrial dynamics. Mitochondrial
      dynamics play critical roles in maintaining mitochondrial function. This review
      focuses on the structure and biological functions of mitochondrial fission and
      fusion related proteins in mammal cells.

PMID- 30112569
TI  - [Role of skeletal muscle fat ectopic deposition in insulin resistance induced by
      high-fat diet].
AB  - Consumption of high-fat diet leads to the increase of fat intake and consequent
      excess storage of fat in the body. When the regular adipose tissues reach their
      capacity to store fat, ectopic fat is stored around and within non-adipose
      tissues, such as the liver and skeletal muscle, which plays important roles in
      glucose metabolism. Hence ectopic fat accumulation in major insulin target
      tissues is a critical determinant of insulin resistance (IR) and various related
      metabolic syndromes. Recent studies have shown that skeletal muscle lipid
      accumulation is more closely related with IR than general obesity and accounts
      for approximately 80%-90% type 2 diabetes, since the skeletal muscle is the
      largest glucose disposal site. Therefore, the association between skeletal muscle
      lipid and IR has attracted more and more research interest. This review
      summarized the role of ectopic skeletal muscle lipid in IR induced by high-fat
      diet and its possible mechanisms.

PMID- 30112570
TI  - [Mechanism of the occurrence of sarcopenia in the elderly].
AB  - The decline in skeletal muscle mass and function with age is referred as
      sarcopenia. It is characterized by the muscle fiber's quality, strength, muscle
      endurance and metabolic ability decreasing as well as the fat and connective
      tissue growing. Previous studies have shown that sarcopenia in itself features
      decreased number and cross-sectional area of muscle fibers and the net
      degradation of protein, which results from the joint effects of multiple factors
      such as the exacerbation of inflammation, oxidative stress injury, mitochondrial
      dysfunction, abnormal autophagy and dysregulation of muscle quality regulatory
      factors. In this review, we systematically displayed the molecular mechanism of
      sarcopenia, which will be helpful to deepen our understanding of sarcopenia and
      provide potential targets for the prevention and treatment of sarcopenia.

PMID- 30112571
TI  - [Voltage-gated sodium channels regulate the biological functions of macrophages].
AB  - Voltage-gated sodium channels (VGSCs) play very important roles in the generation
      and conduction of action potential in the excitable cells. Recent studies have
      showed that VGSCs are also expressed in the macrophages and regulate a variety of
      biological functions, including phagocytosis, endosomal acidification, podosome
      formation, polarization, and antiviral responses, etc. This paper will review the
      roles of VGSCs in regulating the biological functions of macrophages and the
      underlying mechanisms, which would provide clues for the studies of the functions
      of VGSCs in the other immune cells.

PMID- 30112572
TI  - Electrical coupling between hippocampal neurons: contrasting roles of principal
      cell gap junctions and interneuron gap junctions.
AB  - There is considerable experimental evidence, anatomical and physiological, that
      gap junctions exist in the hippocampus. Electrical coupling through these gap
      junctions may be divided into three types: between principal neurons, between
      interneurons and at mixed chemical (glutamatergic)/electrical synapses. An
      approach, combining in vitro experimental with modeling techniques, sheds some
      light on the functional consequences of electrical coupling, for network
      oscillations and for seizures. Additionally, in vivo experiments, using mouse
      connexin knockouts, suggest that the presence of electrical coupling is important
      for optimal performance on selected behavioral tasks; however, the interpretation
      of such data, in cellular terms, has so far proven difficult. Given that
      invertebrate central pattern generators so often depend on both chemical and
      electrical synapses, our hypothesis is that hippocampus-mediated and -influenced
      behaviors will act likewise. Experiments, likely hard ones, will be required to
      test this intuition.

PMID- 30112573
TI  - Brain neuropeptide S: via GPCR activation to a powerful neuromodulator of socio
      emotional behaviors.
AB  - Neuropeptide S (NPS) has attracted the attention of the scientific community due
      to its potent anxiolytic-like and fear-attenuating effects studied in rodents.
      Therefore, NPS might represent a treatment option for neuropsychiatric disorders,
      such as anxiety disorders, even more so as single nucleotide polymorphisms in the
      human NPS receptor gene have been associated with increased anxiety traits that
      contribute to the pathogenesis of fear- and anxiety-related disorders. However,
      the signaling mechanisms underlying the behavioral effects of NPS and the
      interaction with other brain neuropeptides are still rather unknown. To
      illuminate how NPS modulates the expression of selected emotional and social
      behaviors, the present review focuses on neuroanatomical and electrophysiological
      studies, as well as intracellular signaling mechanisms following NPS receptor
      stimulation in rodents. We will also discuss interactions of the NPS system with
      two well-described neuropeptides, namely corticotropin-releasing factor and
      oxytocin, which may contribute to the fear- and anxiety-reducing effects.

PMID- 30112574
TI  - Effect of nociceptin on insulin release in normal and diabetic rat pancreas.
AB  - Nociceptin (NC), also known as Orphanin FQ, is a brain peptide involved in the
      regulation of pain, but its role in the endocrine pancreas is poorly understood.
      The present study examines the pattern of distribution of NC and its effect on
      insulin and glucagon secretion after the onset of diabetes mellitus (DM). Male
      Wistar rats weighing 150-200 g were made diabetic with streptozotocin (60 mg/kg
      body weight, intraperitoneally). Four weeks after the induction of DM, pancreatic
      tissues were retrieved and processed for immunofluorescence, immunoelectron
      microscopy, and insulin and glucagon secretion. Isolated islets from non-diabetic
      and diabetic rats were used to determine the effect of NC on insulin release. NC
      was discerned in islet cells of non-diabetic control and diabetic rat pancreata.
      NC co-localized only with insulin in pancreatic beta cells. NC did not co
      localize with either glucagon or somatostatin or pancreatic polypeptide. The
      number of NC-positive cells was markedly (p < 0.001) reduced after the onset of
      DM. Electron microscopy study showed that NC is located with insulin in the same
      secretory granules of the beta cells of both non-diabetic and diabetic rat
      pancreas. NC inhibits insulin release markedly (p < 0.05) from pancreatic tissue
      fragments of non-diabetic and diabetic rats. In contrast, NC at 10-12 M
      stimulates insulin release in isolated islets of DM rats. In conclusion, NC co
      localizes with insulin only in the islet of Langerhans. The co-localization of NC
      with insulin suggests a role for NC in the regulation of pancreatic beta cell
      function.

PMID- 30112575
TI  - [Quality of patient information leaflets on atopic eczema : An analysis using the
      DISCERN instrument].
AB  - BACKGROUND: As in other chronic diseases, providing medical information plays a
      key role in the therapy of atopic eczema. It is already known that information
      leaflets often do not meet the criteria of evidence-based patient information
      (EBPI). OBJECTIVE: Therefore, the aim of this study was to examine the quality of
      information leaflets on atopic eczema. MATERIAL AND METHODS: A total of 35
      leaflets were included in the study. They were collected from self-aid groups,
      from the internet, from general practitioners, from pediatricians and
      dermatologists as well as from pharmacies in Regensburg. The quality of
      information provided was assessed using the DISCERN instrument. RESULTS: Almost
      all of the 35 patient information leaflets assessed had shortcomings, scoring
      only mid- or low-point in the analysis. None of the leaflets was of excellent
      quality. Only three leaflets were estimated to contain good quality information.
      CONCLUSION: Most of the leaflets did not meet the criteria of evidence-based
      patient information. In conclusion, there may be a lack of quality information
      about atopic eczema. Improving the existing material and comparing the EBPI
      standards with the information needs of atopic eczema patients should be topics
      of future research.

PMID- 30112576
TI  - New steps for treating alcohol use disorder: the emerging importance of physical
      exercise.

PMID- 30112577
TI  - Prazosin during fear conditioning facilitates subsequent extinction in male
      C57Bl/6N mice.
AB  - RATIONALE: Recovery from a traumatic experience requires extinction of cue-based
      fear responses, a process that is impaired in post-traumatic stress disorder.
      While studies suggest a link between fear behavioral flexibility and
      noradrenaline signaling, the role of specific receptors and brain regions in
      these effects is unclear. OBJECTIVES: Here, we examine the role of prazosin, an
      alpha1-adrenergic receptor (alpha1-AR) antagonist, in auditory fear conditioning
      and extinction. METHODS: C57Bl/6N mice were subjected to auditory fear
      conditioning and extinction in combination with systemic (0.1-2 mg/kg) or local
      microinjections (3 or 6 mM) of the alpha1-AR antagonist prazosin into the
      prelimbic division of medial prefrontal cortex or basolateral amygdala.
      Conditioned fear and anxiety-like behaviors were compared with vehicle-injected
      control animals. RESULTS: Mice that received systemic prazosin prior to fear
      conditioning exhibited similar initial levels of cue-elicited freezing compared
      to vehicle controls on the following day. However, at all doses tested, fear that
      was acquired during prazosin treatment was more readily extinguished, whereas
      anxiety-like behavior on the day of extinction was unaffected. A similar pattern
      of results was observed when prazosin was microinjected into the basolateral
      amygdala but not the prelimbic cortex. In contrast to pre-conditioning
      injections, prazosin administration prior to extinction had no effect on
      freezing. CONCLUSIONS: Our results indicate that alpha1-AR activity during
      aversive conditioning is dispensable for memory acquisition but renders
      conditioned fear more impervious to extinction. This suggests that behavioral
      flexibility is constrained by noradrenaline at the time of initial learning via
      activation of a specific AR isoform.

PMID- 30112578
TI  - An exploration of the aversive properties of 2-deoxy-D-glucose in rats.
AB  - Hypoglycemia can alter arousal and negatively impact mood. This study tests the
      hypothesis that acute drops in glucose metabolism cause an aversive state
      mediated by monoamine activity. In experiment 1, male Sprague-Dawley rats were
      either food deprived (FD) or pre-fed (PF) and tested on conditioned place
      avoidance (CPA; biased place conditioning design; 3 pairings drug/vehicle, each
      30 min-long) induced by the glucose antimetabolite 2-deoxy-D-glucose (2-DG; 0,
      300 or 500 mg/kg, SC). Locomotion and blood glucose were also assessed.
      Experiment 2 examined whether clonidine (noradrenergic alpha2 agonist, 0, 10 or
      40 MUg/kg, SC) or bupropion (monoamine reuptake blocker, 0, 10 or 30 mg/kg, SC)
      could alter CPA induced by 500 mg/kg 2-DG. In experiment 3, blood corticosterone
      (CORT) was measured in response to 500 mg/kg 2-DG, alone or in combination with
      40 MUg/kg clonidine or 30 mg/kg bupropion. Finally, experiment 4 controlled for
      possible place conditioning induced by 10 or 40 MUg/kg clonidine, or 10 or 30
      mg/kg bupropion injected without 2-DG. It was found that 2-DG increased blood
      glucose and produced a robust CPA. The feeding status of the animals modulated
      these effects, including CORT levels. Both clonidine and bupropion attenuated the
      effects of 2-DG on CPA and CORT, but only bupropion reversed suppression of
      locomotion. Taken together, these results in rats suggest that impaired glucose
      metabolism can negatively impact arousal and mood via effects on HPA and
      monoamine systems.

PMID- 30112579
TI  - Dimensions of the ciliary muscles of Brucke, Muller and Iwanoff and their
      associations with axial length and glaucoma.
AB  - BACKGROUND: To assess the dimensions of Brucke's muscle, as the longitudinal
      portion, and of Muller's muscle and Iwanoff's muscle combined as circular and
      radial/reticular portions of the ciliary muscle. METHODS: The histomorphometric
      study included human globes that had been enucleated due to an ocular tumor or
      end-stage glaucoma. After immunohistochemical staining of the ciliary muscles,
      the histology slides were examined under a light microscope applying a digitized
      image analysis system. RESULTS: The study included 55 globes [axial length 25.6
      +/- 3.0 mm (range 21.0 mm-36.0 mm)] from 55 patients [mean age, 33.7 +/- 18.3
      years (range:1-66 years)]. Length of Brucke's muscle (mean 3.40 +/- 0.76 mm)
      increased with longer axial length (P < 0.001; regression coefficient beta: 0.52)
      and was not significantly associated with age (P = 0.12), presence of glaucoma (P
      = 0.11) or Brucke's muscle thickness at the scleral spur (P = 0.32), at the site
      of the maximum thickness of the ciliary body (P = 0.84) or at the posterior end
      of Muller's/Iwanoff's muscle (P = 0.66), or with thickness (P = 0.29) and cross
      sectional area (P = 0.85) of Muller's/Iwanoff's muscle. Mean distance between
      Brucke's muscle end and the ora serrata measured 1.73 +/- 1.13 mm and increased
      with longer axial length (P < 0.001; beta: 0.46). Distance from the scleral spur
      to the ora serrata (mean: 4.94 +/- 1.42 mm; range: 3.08-9.09 mm) increased with
      longer axial length (P < 0.001; beta: 0.61). Maximal thickness (mean: 245 +/- 125
      MUm) and cross-section area (mean: 0.19 +/- 0.11 mm2) of Muller's/Iwanoff's
      muscle decreased significantly with the diagnosis of glaucoma (P = 0.02;beta:
      0.38) and longer axial length (P = 0.03; beta: -0.35). CONCLUSIONS: Length of
      Brucke's muscle increased with axial length of the globe, while its cross
      sectional area was independent of axial length. Muller's/Iwanoff's muscle
      decreased in cross-sectional area with longer axis, and in particular with the
      presence of glaucoma, while the dimensions of Brucke's muscle were not related to
      glaucoma.

PMID- 30112581
TI  - A brief report on the clinical trial on neural mobilization exercise for joint
      pain in patients with rheumatoid arthritis.
AB  - BACKGROUND: In rheumatoid arthritis (RA) synovitis, activation of synoviocytes
      and infiltration of adaptive immune cells leads to synovial hyperplasia and joint
      swelling. Under the elevated extra-neural pressure, free nerve endings release
      neuropeptides, calcitonin gene-related peptide, and substance P, thus promoting
      neurogenic inflammation. OBJECTIVE: This study aimed to assess the effect of
      therapeutic neural mobilization (NM) exercises targeting the nervous system on
      disease impact in RA patients. METHODS: A total of 21 RA patients were randomized
      into NM (n = 11) and control (n = 10) groups. NM group patients performed NM
      exercises targeting the median, musculocutaneous, femoral, and saphenous nerve,
      as well as the entire nervous system twice daily for 4-8 weeks. Control RA
      patients performed gentle joint mobilization exercises targeting the same joints.
      Primary outcome was the change in pre-/post-treatment score in the validated
      Rheumatoid Arthritis Impact of Disease (RAID). Secondary outcome was erythrocyte
      sedimentation rate (ESR). RESULTS: There were no significant differences between
      the groups at baseline. No adverse events were observed and compliance was over
      90%. Post-treatment, favorable changes were observed in the NM group RAID score: 
      5.1 vs. -0.8; weighted RAID score: -0.79 vs. -0.15. ESR was reduced in the NM
      group, albeit non-significantly. Regarding the RAID score domains, the NM group
      demonstrated significant improvements in pain and coping. CONCLUSION: The current
      data indicate a beneficial effect of NM exercises on pain and self-efficacy in
      our RA patients. Larger clinical studies are warranted to determine the clinical
      effectiveness of NM as a treatment for pain for RA patients and simultaneously
      address immune and neuropeptide modulation through NM.

PMID- 30112584
TI  - Lowering blood pressure in primary care in Vienna (LOW-BP-VIENNA) : A cluster
      randomized trial.
AB  - BACKGROUND: In Austria only 41% of patients with treated hypertension (HTN) have
      their blood pressure (BP) controlled. This study investigated a strategy to
      improve BP control in primary care. METHODS: General practitioners (GPs) were
      randomized to interventional care vs. standard care and included patients with
      uncontrolled office BP > 140/90 mm Hg. In interventional care, antihypertensive
      therapy was up-titrated using a single pill combination (olmesartan, amlodipine
      and/or hydrochlorothiazde) in 4-week intervals. In standard care, physicians were
      encouraged to treat according to the 2013 European Society of Cardiology
      guidelines for the management of arterial hypertension. The primary endpoint was
      the proportion of patients with controlled office BP < 140/90 mm Hg at 6 months.
      The main secondary endpoint was the improvement in 24 h ambulatory BP (ABPM,
      Clinicaltrials.gov NCT02377661). RESULTS: Between 2015-2017, 20 GPs contributed
      to patient recruitment. The trial was discontinued due to slow recruitment after
      inclusion of 139 eligible patients, 54 of whom were included in the
      interventional group. A significantly larger proportion of patients in
      interventional vs. standard care achieved the office BP target (67% +/- 26% vs.
      39% +/- 29%, respectively, mean difference -27.9%, 95% confidence interval CI 
      54.0%; -1.7%, p = 0.038). The proportion of patients with controlled 24 h ABPM
      (<130/80 mm Hg) was similar between groups (49% +/- 33% vs. 40% +/- 34%,
      respectively, mean difference -8.8%, 95% CI -40.7%; 23.1%, p = 0.57). At
      baseline, pretreated patients received an average of 1.5 +/- 0.8 vs. 1.7 +/- 0.9
      antihypertensive prescriptions. At 6 months, the respective BP reductions were
      achieved with 1.2 +/- 0.5 prescriptions in interventional vs. 2.0 +/- 1.0 in
      standard care (p < 0.01). CONCLUSION: In both groups statistically and clinically
      significant BP reductions were observed after 6 months. In the interventional
      care group, a larger proportion of patients achieved the office BP target
      compared to standard care. The 24 h ambulatory blood pressure levels were
      controlled in 44% of patients at 6 months, without significant differences
      between groups. The respective BP reductions were achieved with a significantly
      lower medication burden in interventional care.

PMID- 30112582
TI  - Updates on Diabetic Foot and Charcot Osteopathic Arthropathy.
AB  - PURPOSE OF REVIEW: Diabetes mellitus affects approximately 30.8 million people
      currently living in the USA. Chronic diabetes complications, including diabetic
      foot complications, remain prevalent and challenging to treat. We review clinical
      diagnosis and challenges providers may encounter when managing diabetic foot
      ulcers and Charcot neuroarthropathy. RECENT FINDINGS: Mechanisms controlling
      these diseases are being elucidated and not fully understood. Offloading is
      paramount to heal and manage diabetic foot ulcers and Charcot neuroarthropathy.
      Diabetic foot ulcers recur and the importance of routine surveillance and
      multidisciplinary approach is essential. Several predictors of failure in Charcot
      foot include a related diabetic foot ulcer, midfoot or rearfoot location of the
      Charcot event, and progressive bony changes on interval radiographs. Patients
      with diabetic foot ulcer and/or Charcot neuroarthropathy are in need of
      consistent and regular special multidisciplinary care. If not diagnosed early and
      managed effectively, morbidity and mortality significantly increase.

PMID- 30112583
TI  - Lymphatic Transport and Lymph Node Location of Microspheres Subcutaneously
      Injected in the Vicinity of Tumors in a Rabbit Model of Breast Cancer.
AB  - PURPOSE: To assess the lymphatic transport of microparticles of 100 nm, 1 MUm and
      10 MUm subcutaneously injected into the breast area of healthy and tumor-bearing
      rabbits, and to analyze their location in lymph node (LN) in relation to
      malignant cells. METHODS: Female rabbits (n = 9) bearing a VX2 tumor in one
      thoracic mammary gland were subcutaneously injected at D15 with polystyrene
      fluorescent particles around the nipple, on the tumor and on the healthy sides.
      The tumor and the LN measured by ultrasound at D9, D15 and D20 were explanted at
      D20. The LN metastases were evaluated by cytokeratin staining. LN uptake of the
      particles was measured by quantifying the green fluorescence surface in hot spot
      regions of healthy and pathologic LN. RESULTS: All animals developed mammary
      tumors. Metastases were found in 39% of LN from the tumor side. LN invasion was
      significantly lower for the 10 MUm group versus the 100 nm group (p < 0.0348).
      The fully invaded area of metastatic LN contained significantly less 100 nm and 1
      MUm particles compared to the low and non-invaded regions and to the healthy LN.
      In the invaded LN, the 1 MUm MS occupied more surface than the 100 nm particles.
      CONCLUSIONS: 1 MUm MS arrived numerously into the areas low-invaded and non
      invaded by the tumoral cells of the pathologic LN, but they were very rare in the
      fully invaded regions. Compared to the 100 nm nanospheres, the 1 MUm were better
      retained (20 times) into the sentinel LN, showing the advantage of micrometric
      particles for lymph-targeted chemotherapy when injected before complete invasion
      by metastases.

PMID- 30112585
TI  - IntuityTM aortic valve thrombosis.

PMID- 30112586
TI  - Update on Devices for Diastolic Dysfunction: Options for a No Option Condition?
AB  - PURPOSE OF REVIEW: This article provides an update on percutaneous devices to
      treat diastolic dysfunction, current clinical experience, and actively enrolling
      trials. We also discuss potential complications and limitations of devices.
      RECENT FINDINGS: Exertional symptoms including exertional dyspnea and exercise
      intolerance are common features of heart failure that are driven by left
      ventricular and left atrial non-compliance that results in pulmonary vascular
      congestion. Multiple studies that have shown that reducing total body volume and
      intravascular pressure, using pharmacologic therapies, are associated with
      improved outcomes among patients who have heart failure with reduced ejection
      fraction (HFrEF) (ejection fraction [EF] < 40%), but not heart failure with
      preserved ejection fraction (HFpEF) (EF > 55%).This is related to the fact that
      HFpEF is associated with altered diastolic compliance but not volume overload,
      which presents as exertional increases in left atrial pressure. Exercise
      assessment of LA and pulmonary pressures are not commonly assessed today in the
      clinic or in the catheterization laboratory. As elevated left atrial pressure
      mediates these symptoms, selective reduction in left atrial pressure may provide
      improvement in symptoms without complications of pharmacologic therapy such as
      diuresis and aggressive blood pressure reduction. Mechanical devices that aim to
      reduce left atrial pressure have been developed and evaluated in HFpEF and HFrEF
      patients. The current data from the small number of patients who have undergone
      treatment with left atrial decompression devices indicate that they have a high
      rate of success and may improve patient's exercise capacity. Larger, controlled
      trials are underway to better understand the role of these devices in patients
      with diastolic dysfunction.

PMID- 30112587
TI  - Tips for Seeing Patients via Telemedicine.
AB  - PURPOSE OF REVIEW: Telemedicine is a technology that permits patients to be seen
      at a distance. This review describes different types of telemedicine, why they
      might be useful for a practice, what equipment is needed, and how to select and
      schedule patients. RECENT FINDINGS: The use of synchronous telemedicine is
      increasing rapidly and has surpassed 50% of ambulatory encounters in some
      instances. Management of patients is particularly germane for an allergy practice
      since it is an outpatient specialty with patients who live in widely distributed
      locations with limited access to allergists. With utilization of digital exam
      equipment, in vitro tests for diagnosis, and spirometry at the patient location,
      there are few clear advantages of seeing patients in-person over virtual visits.
      Telemedicine is here today. As its use increases, it is critical that allergy
      specialists embrace this new technology.

PMID- 30112589
TI  - Cutting Healthcare Costs with Hematoma-Directed Ultrasound-Guided Breast
      Lumpectomy.
AB  - BACKGROUND: Localization of nonpalpable breast lesions for breast-conserving
      surgery (BCS) remains highly variable and includes needle/wire localization (NL),
      radioactive seed localization, radar localization, and hematoma-directed
      ultrasound-guided (HUG) lumpectomy. The superiority of HUG lumpectomy over NL has
      been demonstrated repeatedly in terms of safety, accuracy, low positive margin
      rates, cosmesis, and patient satisfaction. In this study, we evaluate the cost
      effectiveness of HUG lumpectomy over NL for nonpalpable breast lesions. METHODS:
      We performed a retrospective review of 569 patients who underwent lumpectomy at
      the University of Arkansas for Medical Sciences from May 2014 through December
      2017. Lumpectomies were stratified by localization technique, i.e. NL versus HUG.
      A cost-savings estimate was determined for the HUG localization technique, and a
      total amount of dollars saved over the study period was calculated. RESULTS:
      Overall, 569 lumpectomies were performed: 501 (88.0%) via HUG and 68 (12.0%) via
      NL. Intraoperative ultrasound was used in 566 operations (99.5%). Of the
      lumpectomies performed by HUG, 190 lesions (33.4%) were visible only on mammogram
      or breast magnetic resonance imaging prior to diagnostic core needle biopsy
      (CNB). Cost estimates comparing HUG with NL demonstrated a cost savings of
      $497.00 per procedure, the cost of preoperative needle localization by a
      radiologist, and a total of $94,430.00 for the study period. CONCLUSION: In
      utilizing HUG lumpectomy, the initial CNB serves as the diagnostic and
      localization procedure, thus saving time and a painful second procedure on the
      day of operation. HUG lumpectomy is safe, accurate, reduces healthcare costs, and
      results in a better patient experience for the surgical removal of nonpalpable
      breast lesions.

PMID- 30112588
TI  - Proteomic analysis of the defense response to Magnaporthe oryzae in rice
      harboring the blast resistance gene Piz-t.
AB  - BACKGROUND: Rice blast (caused by Magnaporthe oryzae) is one of the most
      destructive diseases of rice. While many blast resistance (R) genes have been
      identified and deployed in rice cultivars, little is known about the R gene
      mediated defense mechanism. We used a rice transgenic line harboring the
      resistance gene Piz-t to investigate the R gene-mediated resistance response to
      infection. RESULTS: We conducted comparative proteome profiling of the Piz-t
      transgenic Nipponbare line (NPB-Piz-t) and wild-type Nipponbare (NPB) inoculated
      with M. oryzae at 24, 48, 72 h post-inoculation (hpi) using isobaric tags for
      relative and absolute quantification (iTRAQ) analysis. Comparative analysis of
      the response of NPB-Piz-t to the avirulent isolate KJ201 and the virulent isolate
      RB22 identified 114 differentially expressed proteins (DEPs) between KJ201
      inoculated NPB-Piz-t (KJ201-Piz-t) and mock-treated NPB-Piz-t (Mock-Piz-t), and
      118 DEPs between RB22-inoculated NPB-Piz-t (RB22-Piz-t) and Mock-Piz-t. Among the
      DEPs, 56 occurred commonly in comparisons KJ201-Piz-t/Mock-Piz-t and RB22-Piz
      t/Mock-Piz-t. In a comparison of the responses of NPB and NPB-Piz-t to isolate
      KJ201, 93 DEPs between KJ201-Piz-t and KJ201-NPB were identified. DEPs in
      comparisons KJ201-Piz-t/Mock-Piz-t, RB22-Piz-t/Mock-Piz-t and KJ201-Piz-t/KJ201
      NPB contained a number of proteins that may be involved in rice response to
      pathogens, including pathogenesis-related (PR) proteins, hormonal regulation
      related proteins, defense and stress response-related proteins, receptor-like
      kinase, and cytochrome P450. Comparative analysis further identified 7 common
      DEPs between the comparisons KJ201-Piz-t/KJ201-NPB and KJ201-Piz-t/RB22-Piz-t,
      including alcohol dehydrogenase I, receptor-like protein kinase, endochitinase,
      similar to rubisco large subunit, NADP-dependent malic enzyme, and two
      hypothetical proteins. CONCLUSIONS: Our results provide a valuable resource for
      discovery of complex protein networks involved in the resistance response of rice
      to blast fungus.

PMID- 30112590
TI  - Bioactive lipid metabolism in platelet "first responder" and cancer biology.
AB  - Platelets can serve as "first responders" in cancer and metastasis. This is
      partly due to bioactive lipid metabolism that drives both platelet and cancer
      biology. The two primary eicosanoid metabolites that maintain platelet rapid
      response homeostasis are prostacyclin made by endothelial cells that inhibits
      platelet function, which is counterbalanced by thromboxane produced by platelets
      during activation, aggregation, and platelet recruitment. Both of these
      arachidonic acid metabolites are inherently unstable due to their chemical
      structure. Tumor cells by contrast predominantly make more chemically stable
      prostaglandin E2, which is the primary bioactive lipid associated with
      inflammation and oncogenesis. Pharmacological, clinical, and epidemiologic
      studies demonstrate that non-steroidal anti-inflammatory drugs (NSAIDs), which
      target cyclooxygenases, can help prevent cancer. Much of the molecular and
      biological impact of these drugs is generally accepted in the field.
      Cyclooxygenases catalyze the rate-limiting production of substrate used by all
      synthase molecules, including those that produce prostaglandins along with
      prostacyclin and thromboxane. Additional eicosanoid metabolites include
      lipoxygenases, leukotrienes, and resolvins that can also influence platelets,
      inflammation, and carcinogenesis. Our knowledge base and technology are now
      progressing toward identifying newer molecular and cellular interactions that are
      leading to revealing additional targets. This review endeavors to summarize new
      developments in the field.

PMID- 30112591
TI  - Pseudomonas aeruginosa FARP72 Offers Protection Against Aeromonas hydrophila
      Infection in Labeo rohita.
AB  - Use of probiotics as the biocontrol agent for disease prevention in aquaculture
      is gaining importance as an alternative to the indiscriminate use of antibiotics
      and other chemotherapeutics. In view of this trend, the probiotic properties of a
      potent antagonistic bacterium, Pseudomonas aeruginosa FARP72, was characterized
      in terms of safety, antagonistic activities, in vitro immunomodulation, and in
      vivo disease resistance. Immunomodulatory activity was ascertained by measuring
      the production of intracellular superoxide anion, nitric oxide, total leukocyte
      peroxidase content, and the leukocyte proliferation in head kidney leukocytes.
      The bacterium isolated from the skin mucus of freshwater catfish Clarias
      batrachus was harmless to Labeo rohita. It showed inhibitory activity against
      Aeromonas caviae, A. hydrophila, Edwardsiella tarda, Pseudomonas putida, and
      Streptococcus agalactiae as revealed by cross and parallel streaking methods.
      Significantly higher superoxide anion and nitric oxide production, peroxidase
      content, and proliferative responses of leucocytes delineated the strains'
      ability to interact with immune cells to activate the immune system in vitro.
      Significant growth inhibition of A. hydrophila from 1.55 * 105 CFU/mL was
      observed when co-cultured with P. aeruginosa FARP72 in phosphate-buffered saline
      (PBS) at levels ranging from 2.61 * 107 to 2.61 * 109 CFU/mL in 10 days. P.
      aeruginosa FARP72 increased the survival rate of rohu fingerlings against
      pathogenic A. hydrophila challenge in biocontrol study in vivo as determined by
      cohabitation challenge. These results suggest that P. aeruginosa FARP72 is a
      potential probiotic strain and can be used in aquaculture to improve the health
      status and disease resistance of fish.

PMID- 30112592
TI  - Morphological classification and dynamics of a two-dimensional drop sliding on a
      vertical plate.
AB  - A two-dimensional drop sliding down a plate under the action of gravity is
      numerically studied. A lattice Boltzmann method coupled with the phase field
      method is utilized, which can well capture the motion of the three-phase contact
      line. The morphologies of the sliding drop and corresponding force balance during
      the process are considered. It is found that there are two basic sliding modes of
      the drop with various gravitational and viscous effects. The viscous shear stress
      ( [Formula: see text] from the wall acts on the bottom of the drop, and it is
      divided in two parts. One is in the contact line region, and the other on the
      rest part of the solid-liquid interface (contacting area). The former one appears
      as [Formula: see text] -peaks, which are purely determined by the intrinsic
      contact angle ( [Formula: see text] and sliding speed. They are very local. When
      the gravity is small, the drop slides down very slowly, and such shear force can
      balance the gravity. Meanwhile, the shape of the droplet can be interestingly
      characterized as a "pendant drop". When the gravity increases, an additional
      shear force is generated mainly due to the appearing of a trail at the rear part
      of the drop. The de-wetting failure condition makes the sliding velocity almost
      constant in this regime. The present study is also valuable to understand the
      physics of three-dimensional drop sliding.

PMID- 30112594
TI  - Maternal Trauma Exposure and Childhood Anxiety Outcomes: Examining Psychosocial
      Mechanisms of Risk.
AB  - The current study aimed to explore the relationship between maternal exposure to
      various types of trauma and child anxiety outcomes, and to investigate maternal
      depression and parenting quality as potential mediators of these relationships.
      Aims were examined within a sample of 185 mother-child dyads who participated in
      a longitudinal study assessing maternal trauma history, maternal depression, and
      parenting quality at preschool age (ages 2.5 to 5.5 years), and for whom maternal
      and secondary caregiver reports of child anxiety were obtained at school age
      (ages 6 to 11 years). Hypotheses were that (1) maternal exposure to trauma would
      be positively associated with anxiety levels in offspring and that (2) parenting
      quality and maternal depression would mediate the relationship between maternal
      exposure to trauma and child anxiety. Results suggest a direct association
      between maternal trauma history and child anxiety, as well as indirect
      associations through parenting quality and maternal depression. These findings
      are discussed with regard to their implications for the prevention of child
      anxiety, as well as their implications for the advancement of the literature on
      intergenerational effects of trauma.

PMID- 30112593
TI  - Transgender medicine - puberty suppression.
AB  - Puberty suppression is the reversible first step of endocrine medical treatment
      in transgender youth, and allows for two very important aspects of transgender
      management. Firstly, it buys the patient, family and their medical team time to
      fully evaluate the presence and persistence of gender dysphoria. Secondly, it
      successfully prevents the development of cis-gender unwanted secondary sexual
      characteristics. The latter, when present, almost certainly increase the burden
      of psychological co-morbidity for any transgender person. This management is
      modelled from treatment of gonadotropin-dependent precious puberty, with use of
      GnRH agonists at its core. With the increasing number of transgender youth
      treated, and the changing demographics of patients seeking medical care,
      providers are faced with the decision to start puberty blockade at younger ages
      than previous decades. This article will review the rationale behind puberty
      blockade for transgender children, the providers' options for achieving this
      goal, the emerging literature for potential adverse effects on such an approach,
      as well as identify directions of potential future research.

PMID- 30112595
TI  - Extinction Learning as a Potential Mechanism Linking High Vagal Tone with Lower
      PTSD Symptoms among Abused Youth.
AB  - Childhood abuse is a potent risk factor for psychopathology, including
      posttraumatic stress disorder (PTSD). Research has shown high resting vagal tone,
      a measure of parasympathetic nervous system function, protects abused youth from
      developing internalizing psychopathology, but potential mechanisms explaining
      this effect are unknown. We explored fear extinction learning as a possible
      mechanism underlying the protective effect of vagal tone on PTSD symptoms among
      abused youth. We measured resting respiratory sinus arrhythmia (RSA) and skin
      conductance responses (SCR) during a fear conditioning and extinction task in
      youth with variability in abuse exposure (N = 94; aged 6-18 years). High RSA
      predicted lower PTSD symptoms and enhanced extinction learning among abused
      youths. In a moderated-mediation model, extinction learning mediated the
      association of abuse with PTSD symptoms only among youth with high RSA. These
      findings highlight extinction learning as a possible mechanism linking high vagal
      tone to decreased risk for PTSD symptoms among abused youth.

PMID- 30112596
TI  - Response Inhibition, Response Execution, and Emotion Regulation among Children
      with Attention-Deficit/Hyperactivity Disorder.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is associated with deficits in
      response inhibition, response execution, and emotion regulation. However, the
      nature of the associations among these deficits remains unclear. Thus, this study
      examines these associations using a multi-method design. One hundred sixty-six
      children (aged 5-13 years; 66.3% male; 75 with ADHD) completed two conditions
      (i.e., neutral and fear) of an emotional go/no-go task. Parasympathetic-based
      regulation was indexed via respiratory sinus arrhythmia (RSA), and sympathetic
      based reactivity was indexed via cardiac pre-ejection period (PEP). Overall,
      children exhibited more difficulty with response execution (i.e., more omission
      errors, fewer correct go responses) and less difficulty with response inhibition
      (i.e., fewer commission errors, more correct no-go responses) during the fear
      condition than the neutral condition. Children with ADHD displayed more
      difficulty with response execution during the fear condition compared to
      typically developing youth. Additionally, children with ADHD displayed
      parasympathetic-based dysregulation (i.e., RSA increase from baseline) and
      reduced sympathetic-based reactivity (i.e., PEP lengthening) compared to
      typically developing youth across task conditions. In sum, children with ADHD
      demonstrate greater difficulty with response execution during emotionally salient
      contexts, as well as parasympathetic-based emotion dysregulation. Future work
      should examine these associations longitudinally with the aim of predicting
      impairment and treatment response in youth with ADHD.

PMID- 30112597
TI  - Tools of engagement: Information seeking in chimpanzees.
AB  - Two widely studied and impressive cognitive feats in nonhuman animals,
      metacognition and tool use, both require the cognitive tools of monitoring and
      controlling knowledge states and adaptive actions toward desirable outcomes. In a
      recent study, Perdue, Evans, and Beran (PLoS ONE, 13(4), e0193229, 2018) found
      that some chimpanzees used tools to selectively acquire information and make
      inferences, indicating metacognitive awareness and appropriate use of tools
      depending on the content of those knowledge states.

PMID- 30112598
TI  - Dogs do not demonstrate a human-like bias to defer to communicative cues.
AB  - Human children and domesticated dogs learn from communicative cues, such as
      pointing, in highly similar ways. In two experiments, we investigate whether dogs
      are biased to defer to these cues in the same way as human children. We tested
      dogs on a cueing task similar to one previously conducted in human children. Dogs
      received conflicting information about the location of a treat from a Guesser and
      a Knower, who either used communicative cues (i.e., pointing; Experiments 1 and
      2), non-communicative physical cues (i.e., a wooden marker; Experiment 1), or
      goal-directed actions (i.e., grasping; Experiment 2). Although human children
      tested previously struggled to override inaccurate information provided by the
      Guesser when she used communicative cues, in contrast to physical cues or goal
      directed actions, dogs were more likely to override the Guesser's information
      when she used communicative cues or goal-directed actions than when she used non
      communicative physical cues. Given that dogs did not show the same selective bias
      towards the Guesser's information in communicative contexts, these findings
      provide clear evidence that dogs do not demonstrate a human-like bias to defer to
      communicative cues. Instead, dogs may be more likely to critically evaluate
      information presented via communicative cues than either physical or non
      communicative cues.

PMID- 30112600
TI  - The Impact of Bariatric Surgery on Cardiopulmonary Function: Analyzing VO2
      Recovery Kinetics.
AB  - PURPOSE: To assess cardiopulmonary capacity, autonomic heart function, and oxygen
      recovery kinetics during exercise testing before and after bariatric surgery.
      METHODS: This is a prospective cohort study. Symptom-limited cardiopulmonary
      exercise testing was performed with 24 patients, 1 week before and 4 months after
      bariatric surgery. The main variables were maximum oxygen uptake (VO2 max), the
      time elapsed until the appearance of the first ventilatory threshold (TLV1), and
      VO2 oxygen kinetics during recovery with a 50% reduction in peak oxygen uptake in
      the recovery period after exercise (50%VO2RP). RESULTS: The study demonstrated
      that the peak VO2?kg increased significantly after bariatric surgery. When
      analyzed without adjusting for weight, the peak VO2 paradoxically and
      significantly decreased after the surgical procedure (p = 0.007). The exercise
      time until the anaerobic threshold was longer after surgical procedure than
      before it (p = 0.001). Regarding post-exercise oxygen recovery kinetics, there
      was a faster reduction in the peak oxygen uptake after bariatric surgery than
      before the procedure (p < 0.001). CONCLUSIONS: There was an obvious cardiac
      autonomic improvement after surgery. Despite the improvement in exercise
      tolerance, patients undergoing bariatric surgery had lower maximum oxygen
      consumption in the analysis not corrected for body weight. The mean VO2RP before
      bariatric surgery was 141 s and was 111 s after the surgical procedure (p <
      0.001). These results suggest an improvement in the recovery kinetics of oxygen
      consumption, a novel index of cardiac reserve capacity, on patients undergoing
      bariatric surgery.

PMID- 30112599
TI  - Roux-en-Y Gastric Bypass Is More Effective than Sleeve Gastrectomy in Improving
      Postprandial Glycaemia and Lipaemia in Non-diabetic Morbidly Obese Patients: a
      Short-term Follow-up Analysis.
AB  - PURPOSE: We aimed to compare the effects of Roux-en-Y gastric bypass (RYGB) and
      sleeve gastrectomy (SG) on postprandial glucose and lipid metabolism in addition
      to weight loss and fasting metabolic profile, in non-diabetic patients undergoing
      bariatric surgery. METHODS: Seventy-one patients were consecutively recruited and
      studied preoperatively, 3 and 6 months after surgery. Of these, 28 underwent RYGB
      (7 males, age 38 +/- 9 years, BMI 46.9 +/- 5.0 kg/m2), and 43 SG (9 males, age 38
      +/- 9 years, BMI 50.2 +/- 7.0 kg/m2). A semi-liquid mixed meal was consumed, and
      blood samples were taken before, and every 30 min after meal ingestion up to 180
      min postprandially, for measurement of glucose, insulin, and lipids. The overall
      postprandial response was assessed as area under the concentration-time curve
      (AUC). RESULTS: Baseline metabolic parameters were similar between RYGB and SG.
      Both groups experienced comparable weight loss, and a similar improvement in
      fasting glucose, insulin, and insulin resistance. Total and LDL cholesterol
      levels were lower at 6 months after RYGB compared to SG, while there was no
      difference in HDL cholesterol or triglycerides. Glucose AUC was lower after RYGB
      compared to SG at both 3 (p = 0.008) and 6 months (p = 0.016), without any
      difference in postprandial insulin response. Triglyceride AUC was also lower in
      RYGB vs. SG at 3 and 6 months (p <= 0.001). CONCLUSIONS: RYGB is superior to SG
      in improving postprandial glycaemia and lipaemia and cholesterol profile 6 months
      postoperatively in non-diabetic, severely obese patients. These findings imply
      procedure-specific effects, such as the malabsorptive nature of RYGB, and less
      likely a different incretin postoperative response.

PMID- 30112601
TI  - Laparoscopic Gastric Greater Curvature Plication: Intermediate Results and
      Factors Associated with Failure.
AB  - BACKGROUND: Laparoscopic gastric greater curvature plication (LGGCP) is a novel
      bariatric procedure. Few studies have presented intermediate or long-term
      results. The aim of this prospective study was to investigate intermediate
      results and factors associated with failure to achieve satisfactory weight loss
      after LGGCP. METHODS: Between October 2011 and November 2013, 61 patients
      underwent LGGCP and were followed up to 36 months after operation. Demographics,
      comorbidities, complications, and percentage of excess body mass index loss
      (%EBMIL) were analyzed. Logistic regression analysis was used to determine
      independent risk factors for weight loss failure 3 years after LGGCP. RESULTS:
      Forty-eight women and 13 men with an average age of 47.7 +/- 10.3 years and
      preoperative BMI of 46.3 +/- 5.8 underwent LGGCP. Postoperative complications
      were observed in three patients (4.9%) and two of them (3.3%) underwent
      reoperations. Follow-up rate was 95%, 91.7, and 88.3% after 1, 2, and 3 years,
      respectively. Average %EBMIL after 1 year was 47.25 +/- 21.6, 44.8 +/- 25.9 after
      2 years, and 41.9 +/- 25.6 after 3 years. Gastroscopy 3 years after LGGCP
      demonstrated intact plication fold in 55% of cases. Preoperatively, GERD was
      present in 46% of patients. Prevalence of GERD 3 years after LGGCP was 34.6%.
      Remission rates of type 2 diabetes mellitus and hypertension were 27.8 and 38.3%,
      respectively. Higher postoperative hunger sensation was found to be an
      independent factor (OR 1.6, 95% 1.141-2.243; p = 0.002) associated with
      unsatisfactory weight loss after LGGCP. CONCLUSIONS: Patients with LGGCP had
      postoperative complication rate 4.9% and achieved only modest weight loss after 3
      years. Increased hunger was an independent risk factor associated with
      unsatisfactory weight loss after LGGCP. Long-term follow-up data are needed to
      define the role of LGGCP in the treatment of morbid obesity.

PMID- 30112602
TI  - Reply to: Yet Another Mortality with a Bilio-Pancreatic Limb of > 200 cm with One
      Anastomosis Gastric Bypass.

PMID- 30112603
TI  - Effects of Cognitive Behavioral Therapy on Eating Behaviors, Affective Symptoms,
      and Weight Loss After Bariatric Surgery: a Randomized Clinical Trial.
AB  - BACKGROUND: The long-term effects of presurgical psychological interventions on
      weight loss, eating behaviors, affective symptoms, and health-related quality of
      life remain uncertain. This study aimed to assess the 4-year effects of cognitive
      behavioral therapy (CBT) before bariatric surgery on these outcomes. METHODS:
      Single-center randomized controlled parallel-group trial. Patients were assessed
      after CBT before bariatric surgery (n = 98) and 1 year (n = 80) and 4 years (n =
      61) after surgery. The intervention group received a 10-week preoperative
      individual CBT focusing on self-monitoring to identify triggers of dysfunctional
      eating behaviors in order to improve regulation of eating as well as the breaking
      of the interrelationship between eating behaviors, negative mood, and
      dysfunctional cognitions. RESULTS: The 61 patients (70% women) had a mean (SD)
      age of 42.4 (10.1) years and BMI 43.5 (4.4) kg/m2. Preoperative CBT was not
      associated with 1- and 4-year reduction of dysfunctional eating behaviors,
      affective symptoms and body weight, or improved health-related quality of life.
      Patients with minor or considerable symptoms of depression receiving CBT had
      lower mean BMI than controls, both before surgery, - 1.1 kg/m2, and - 1.5 kg/m2,
      and 4-years after surgery, - 2.9 kg/m2 and - 7.5 kg/m2, respectively. CONCLUSION:
      Presurgical CBT was not associated with better long-term outcomes. However, in
      patients with minor or considerable symptoms of depression, CBT was associated
      with lower body weight before and 4 years after surgery. Additional studies are
      required to verify whether patients with symptoms of depression should be offered
      CBT before and/or after bariatric surgery, and which clinical aspects the CBT
      should address. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01403558.

PMID- 30112604
TI  - Sleeve Gastrectomy for Obesity in Polycystic Ovarian Syndrome: a Pilot Study
      Evaluating Weight Loss and Fertility Outcomes.
AB  - PURPOSE: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder
      associated with obesity and infertility. Gastric bypass has been shown to be
      effective in treating these symptoms. However, the efficacy of vertical sleeve
      gastrectomy (VSG) has not been studied in the PCOS population. This study
      analyzed weight loss and fertility outcomes of VSG in this population. METHODS: A
      retrospective review of patients with PCOS and without PCOS (CON) undergoing VSG
      from 2008 to 2016 was performed at two bariatric centers. BMI and percent excess
      weight loss (%EWL) were collected at 3, 6, and 12 months postoperatively. Patient
      characteristics and postoperative pregnancy status were compared between the two
      cohorts. RESULTS: One hundred nineteen PCOS patients were compared to 119 CON
      patients. Similar attrition rates were seen between cohorts at 3-month (5 vs 8%),
      6-month (13 vs. 14%), and 12-month (18 vs. 13%) evaluation. PCOS patients had
      greater DeltaBMI at 3 months (- 7.64 vs. - 6.82; p = 0.05), 6 months (- 10.56 vs.
      - 9.49; p = 0.02), and 12 months (- 12.43 vs. - 11.49; p = 0.04). PCOS patients
      also had greater %EWL at 12 months compared to CON (66 vs 60%; p = 0.05). Twenty
      two percent of PCOS patients became pregnant within 12 months, 69% of which were
      previously nulliparous. CONCLUSION: Compared to non-PCOS patients, PCOS patients
      had greater postoperative DeltaBMI and %EWL at 1 year. The majority of patients
      becoming pregnant after VSG were previously nulliparous. This study shows that
      VSG is effective for weight loss in PCOS patients with obesity and may positively
      augment effect fertility rates.

PMID- 30112605
TI  - Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an
      international expert consensus initiative for improvement of animal modeling in
      sepsis.
AB  - BACKGROUND: Pre-clinical animal studies precede the majority of clinical trials.
      While the clinical definitions of sepsis and recommended treatments are regularly
      updated, a systematic review of pre-clinical models of sepsis has not been done
      and clear modeling guidelines are lacking. OBJECTIVE: To address this deficit, a
      Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in
      May 2017. The goal of the conference was to identify limitations of pre-clinical
      sepsis models and to propose a set of guidelines, defined as the "Minimum Quality
      Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational
      value of these models. METHODS: A total of 31 experts from 13 countries
      participated and were divided into 6 thematic working groups (WG): (1) study
      design, (2) humane modeling, (3) infection types, (4) organ failure/dysfunction,
      (5) fluid resuscitation, and (6) antimicrobial therapy endpoints. As basis for
      the MQTiPSS discussions, the participants conducted a literature review of the
      260 most highly cited scientific articles on sepsis models (2002-2013). RESULTS:
      Overall, the participants reached consensus on 29 points; 20 at "recommendation"
      (R) and 9 at "consideration" (C) strength. This executive summary provides a
      synopsis of the MQTiPSS consensus (Tables 1, 2, and 3). Detailed commentaries to
      all Rs and Cs are simultaneously published in three separate full-length papers.
      CONCLUSIONS: We believe that these recommendations and considerations will serve
      to bring a level of standardization to pre-clinical models of sepsis and
      ultimately improve translation of pre-clinical findings. These guideline points
      are proposed as "best practices" for animal models of sepsis that should be
      implemented. In order to encourage its wide dissemination, this article is freely
      accessible in Shock, Infection and Intensive Care Medicine Experimental.

PMID- 30112606
TI  - Effect of early fluid resuscitation combined with low dose cyclophosphamide on
      intestinal barrier function in severe sepsis rats.
AB  - To investigate the effect of early fluid resuscitation on intestinal microecology
      in rats with severe sepsis. The severe sepsis model used was mainly cecal
      ligation perforation (CLP) model. Male SD rats were randomly divided into five
      groups: sham, CLP, CLP + normal saline (NS), CLP + cyclophosphamide (CTX), and
      CLP + NS + CTX. (1) The levels of IL-6, IL-10, and TNF-alpha in peripheral blood
      were measured by ELISA. (2) The expression of occludin/beta-action in colonic
      tissue of mice was examined by Western Blot. (3) The intestinal permeability was
      measured by FD70 detection. (4) The length of the chorionic membrane was measured
      by colon histopathological staining. (5) The intestinal epithelial cell apoptosis
      was measured with the apoptosis index. (1) The rat model of severe sepsis was
      successfully replicated, and the 7-day survival rate of sepsis mice in each group
      was analyzed. (2) The expression level of splenic junction protein and the
      pathological damage in colonic tissue of the severe sepsis mice was significantly
      different between sham, CLP, CTX, NS, and NS + CTX (P < 0.05). The expression of
      tight junction protein in the NS + CTX mice was the highest, and the pathological
      damage was the smallest. (3) The colonic tissue apoptosis and intestinal
      permeability in the severe sepsis mice were compared with those of the colon
      tissues (P < 0.05). (4) The expression levels of IL-6, IL-10, and TNF-alpha in
      peripheral blood were significantly increased after severe sepsis (P < 0.01). The
      expression of IL-6 and TNF-alpha in each treatment group decreased (P < 0.05),
      while the expression of IL-10 in NS + CTX group increased significantly (P <
      0.01). (1) We successfully replicated the rat model of severe sepsis. (2) Early
      fluid intervention and cyclophosphamide treatment can significantly improve the 7
      day survival rate of the sepsis mice. (3) The fluid resuscitation and
      cyclophosphamide can delay intestinal damage to the intestinal tract barrier
      function and play a protective role.

PMID- 30112608
TI  - Clinical and prognostic role of detection timing of distant metastases in
      patients with differentiated thyroid cancer.
AB  - PURPOSE: Distant metastases (DM) from DTC occur in 5-25% of cases and are
      correlated to lower survival; the prognostic significance of the temporal onset
      of DM is unclear. Our aim was to retrospectively analyze the prevalence of DM and
      to assess the prognostic role of the timing of manifestation of DM regarding the
      outcome. MATERIALS AND METHODS: We included 174 patients (mean age 64 years).
      According to the time of manifestation, DM were divided in two groups:
      synchronous DM (SDM, n = 108) defined as metastases present at initial diagnosis
      and metachronous DM (MDM, n = 66) as diagnosed during follow-up. SDM were further
      sub grouped in pre-RAIT when diagnosed during pre-surgery work-up (n = 35) and
      baseline-RAIT when detected by first whole body scan after RAIT (n = 73). Disease
      specific survival (DSS) was analyzed using the Kaplan-Meier method. RESULTS:
      Total RAI activities and number of treatments were significantly higher in MDM,
      also loss of RAI avidity was more frequent in MDM. Forty-four patients died
      during follow-up, of which 41 were DTC-related deaths, 5-year and 10-year DSS
      were 80% and 56%. On univariate analysis MDM had significantly shorter DSS; also
      histotype and RAI avidity were significant risk factors of impaired survival. On
      multivariate analysis, only loss of RAI avidity remained as independent negative
      predictor (p = 0.043). Considering SDM, DSS was significantly shorter in pre-RAIT
      group than baseline-RAIT (p = 0.004). Instead there was no significant difference
      between pre-RAIT-SDM and MDM in survival outcome (p = 0.875). CONCLUSIONS: In DTC
      with DM, loss of RAI uptake has an important role in survival. No significant
      difference in survival outcome was discovered between SDM and MDM; but, among
      SDM, pre-RAIT had significant shorter DSS than baseline-RAIT.

PMID- 30112609
TI  - Correction to: Discussion of Shue et al. "Fat Injection: A Systemic Review of
      Injection Volumes by Facial Subunit".
AB  - Dino Elyassnia was left off the original version of this article. The author line
      is correct here.

PMID- 30112607
TI  - Chitosan-based binary dry powder inhaler carrier with nanometer roughness for
      improving in vitro and in vivo aerosolization performance.
AB  - Suitable nanometer roughness favors interactions between drugs and carriers, and
      it is a promising approach to enhance the aerosolization performance of carrier
      based dry powder inhalers (DPIs). In this study, by altering the molecular
      migration rates, chitosan-based binary carriers (CBBCs) with nanometer roughness
      were fabricated for DPIs. Comprehensive physicochemical characterizations were
      conducted to elucidate the formation mechanism of the CBBCs. It was hypothesized
      that different constituent ratios in the formulations would result in different
      assembling of the particles and diverse roughness scales. The fine particle
      fractions (FPF, approximately 40~60%) of nanometer roughness CBBC-based DPI
      formulations were satisfactory, demonstrating the enhancement of the in vitro
      aerodynamic performance. The positive correlation (R2 = 0.9883) between the
      nanometer roughness and FPF was revealed, and the surface roughness of 20 nm
      might achieve the best aerosolization performance. CBBCs (optimal formulations)
      showed no difference in cytotoxicity on A549 and Calu-3 cells (p > 0.05).
      Additionally, the increased Cmax and AUC0-8h of the formulation with the
      nanometer roughness (p < 0.05) were observed in pharmacokinetic studies, which
      resulted from the improved in vivo aerosolization performance. In summary, the
      CBBCs were a prospective tool to improve the in vitro and in vivo aerosolization
      performance of DPIs. Graphical abstract ?.

PMID- 30112610
TI  - Flood inundation mapping and monitoring in Kaziranga National Park, Assam using
      Sentinel-1 SAR data.
AB  - Satellite-based flood assessment for extent and severity is very crucial input
      before, during, and after a flood event has occurred. Though optical remote
      sensing data has been widely used for flood hazard mapping, Synthetic Aperture
      Radar (SAR) data is preferred for detecting inundated areas and providing
      reliable information during a flood event due to its capability to operate in all
      weather and day/night time. Availability of cloud-free optical images during
      monsoon over north eastern India is a rarity. SAR data also has the advantage of
      detecting inundation under vegetated areas due to its penetration capabilities
      and sensitivity to soil moisture. The present study is an attempt to use SAR data
      for flood monitoring of the Kaziranga National Park (KNP) during monsoon, 2017.
      Every year, animals are washed away by floods and most of them migrate to higher
      grounds in order to escape from the rising water levels. Flooding events are
      common in the study area during the monsoon season due to high rainfall and its
      close proximity to the Brahmaputra River. Dual polarized (VV and VH) Sentinel-1
      SAR images obtained for the entire monsoon period in 2017 were used to create
      inundation maps of the KNP. Two flood waves were observed in July and August, the
      second of which is considered to be one of the worst flooding events inundating
      most areas of the park. The use of SAR data for monitoring of flood events can be
      very crucial for identifying locations for building animal shelters and finding
      routes for rescue and relief operations during the disaster.

PMID- 30112611
TI  - Assessing variation in technique for sleeve gastrectomy based on outcomes of
      surgeons ranked by safety and efficacy: a video-based study.
AB  - BACKGROUND: Considerable technical variation exists when performing laparoscopic
      sleeve gastrectomy (LSG). However, little is known about which techniques are
      associated with optimal outcomes. OBJECTIVE: To compare technical variation among
      surgeons with the lowest complication rates and whose patients achieved the most
      weight loss. METHODS: Practicing bariatric surgeons (n = 30) voluntarily
      submitted a video of a typical LSG performed between 2015 and 2016. Technique
      specific data captured from videos and a questionnaire included bougie size,
      stapler vendor, number of staple loads, use of staple line reinforcement, fibrin
      sealant, intraoperative leak test, endoscopy, and drain placement. Surgeon
      specific outcomes were obtained from cases performed by surgeons during the study
      period (n = 7023) using a state-wide bariatric-specific data registry. Surgeons
      were ranked based on 30-day risk-adjusted surgical complication rates ("safety")
      and excess body weight loss (EBWL) % ("efficacy") at 1 year after surgery.
      Technique-specific variables were compared between surgeons ranked in the top and
      bottom quartile for both safety and efficacy. RESULTS: Surgical complication
      rates ranged from 0 to 4.32% while EBWL varied from 45.3 to 65.3%. There was no
      correlation between surgeon rankings for safety and efficacy (Pearson's r =
      0.063, p = 0.741). Surgeons ranked in the top quartile for safety and efficacy
      had significantly shorter mean operative times than surgeons ranked in the bottom
      quartile (65 min vs. 69 min, p < 0.0001). Surgeons with the highest leak rates
      were more likely to use buttressing (85.7% vs 40.0%, p = 0.032), otherwise
      operative techniques varied considerably. CONCLUSIONS: Technical variation
      appears to have minimal effect on the safety or efficacy of sleeve gastrectomy
      among surgeons participating in a state-wide quality improvement collaborative.
      Top ranked surgeons did have faster mean operative times indicating that there
      may be other metrics of technical quality that correlate to optimal outcomes.

PMID- 30112612
TI  - Educating Hispanics About Clinical Trials and Biobanking.
AB  - Hispanics are under-represented in clinical research. To ensure that the Hispanic
      population benefits from advances in public health and medicine, including
      personalized medicine, there is a need to increase their participation in
      clinical trials and biobanking. There is a great need for improving awareness and
      addressing concerns individuals may have about participation. The purpose of this
      study was to adapt, implement, and evaluate educational materials about clinical
      trials and biobanking for Hispanic individuals. We adapted existing materials
      based on focus group data. We then trained four promotoras de salud to deliver
      education to Hispanic adults in community settings in Houston, TX. The promotoras
      educated 101 Hispanic adults, 51 on biobanking and 50 on clinical trials. Study
      staff administered brief pre- and post-test questionnaires that measured
      benefits, barriers, norms, self-efficacy, and intention to participate in either
      clinical trials or biobanking. Our sample was predominately female (83%) and
      Spanish-speaking (69%) and made less than $25,000 a year (87%). This intervention
      increased perceived benefits of participating in biobanking and clinical trials,
      self-efficacy for donating biospecimens, and intention to participate in
      biobanking if invited. Perceived barriers to participating declined. This study
      demonstrated that brief education can result in improved perceptions and
      attitudes related to participation in biobanking and clinical trials, and could
      increase participation. Researchers and practitioners could use these educational
      materials to educate Hispanic community members on clinical research potentially
      increasing participation rates in the future.

PMID- 30112613
TI  - Comparison of long-pulsed Nd: YAG laser with cryotherapy in treatment of acral
      warts.
AB  - Acral warts are considered as prevalent reasons for dermatologic consultations
      and remain an important continuing challenge until now because there is no
      consensus about optimal therapeutic modality. This study investigated the
      efficacy of long-pulsed Nd: YAG laser therapy and cryotherapy in treatment of
      acral warts. Patients who underwent treatment with cryotherapy or long-pulsed Nd:
      YAG laser therapy for symmetrical and bilateral warts on the extremities (hand
      and foot) that is confirmed by an expert dermatologist from May 2016 until March
      2018 were assessed for enrollment in our study. Laser and cryotherapy sessions
      were applied every 2 weeks for a maximum of six sessions. Patients followed up
      and evaluated 3 months after the last treatment. Data were analyzed by SPSS
      (v.21. IBM Inc. IL). The P value less than 0.05 was considered significant. From
      60 enrolled patients, 134 lesions were treated using cryotherapy and 114 other
      lesions treated with laser beam. Thirty-four males (average age 26.85 +/- 7.528
      years) and 26 females (average age 26.73 +/- 5.640 years) participated. Finally,
      it was a significant reduction in both lesion width (P = 0.000) and length (P =
      0.000) after the sessions of cryotherapy. The width and length of lesions is
      reduced significantly after each session of laser therapy similarly (P = 0.000).
      Cryotherapy and long-pulsed Nd: YAG laser are effective on the reduction of both
      width and length of lesions. Clinically, the methods are not different in their
      ultimate effects.

PMID- 30112614
TI  - Strategic Pentablock Copolymer Nanomicellar Formulation for Paclitaxel Delivery
      System.
AB  - Nanomicelles (NM) enhance solubility and absorption of active pharmaceutical
      ingredients (APIs). Various polymers and non-polymers are utilized to prepare
      nanomicellar formulations to achieve high absorption and delivery of drugs. The
      main purpose of this study was to develop drug-loaded nanomicelles with
      pentablock copolymers for paclitaxel delivery. Monomers of lactide, epsilon
      caprolactone, and polyethylene-glycol were utilized to prepare pentablock
      copolymer by ring opening technique. The pentablock nanomicelles (PBNM) were
      formulated by evaporation and rehydration. Both copolymers and nanomicelles were
      analyzed by H-NMR, FTIR, and XRD. Nanomicelles were further analyzed for size and
      zeta potential using dynamic light scattering (DLS) and by H-NMR and TEM. The
      XRD, FTIR, and H-NMR analyses confirmed the structures of the pentablock
      copolymers. Average size was 20 nm +/- 5.00 nm, and zeta-potential is around
      zero. H-NMR and FTIR analyses for Paclitaxel-PBNM indicated peaks of paclitaxel
      and the polymer, confirming successful encapsulation. TEM showed spherical
      morphology and size range similar to that obtained by DLS. In vitro release
      studies revealed slow first-order paclitaxel release rate from pentablock
      nanomicelles in phosphate buffer solution (PBS). Confocal laser scanning
      microscopy analysis with coumarin-6-loaded in PBNM indicated that pentablock
      nanomicelles were efficiently taken into prostate cancer (PC-3) cells. Cell
      proliferation assay showed that nanomicelles were able to ferry adequate amounts
      of paclitaxel drug into PC-3 cells and subsequently inhibiting PC-3 cell
      proliferation significantly. Results confirmed that pentablock copolymer can
      generate drug-loaded nanomicelles with desirable sizes and zeta potential. These
      demonstrate potentiality of pentablock nanomicelles as carrier for anticancer
      delivery.

PMID- 30112615
TI  - Branched Chain Amino Acids in Metabolic Disease.
AB  - PURPOSE OF REVIEW: Elevations in circulating branched chain amino acids (BCAAs)
      have gained attention as potential contributors to the development of insulin
      resistance and diabetes. RECENT FINDINGS: Epidemiological evidence strongly
      supports this conclusion. Suppression of BCAA catabolism in adipose and hepatic
      tissues appears to be the primary drivers of plasma BCAA elevations. BCAA
      catabolism may be shunted to skeletal muscle, where it indirectly leads to FA
      accumulation and insulin resistance, via a number of proposed mechanisms. BCAAs
      have an important role in the development of IR, but our understanding of how
      plasma BCAA elevations occur, and how these elevations lead to insulin
      resistance, is still limited.

PMID- 30112617
TI  - ESNR 2018.

PMID- 30112616
TI  - Cardiac automaticity: basic concepts and clinical observations.
AB  - PURPOSE: The purpose of this report was to review the basic mechanisms underlying
      cardiac automaticity. Second, we describe our clinical observations related to
      the anatomical and functional characteristics of sinus automaticity. METHODS: We
      first reviewed the main discoveries regarding the mechanisms responsible for
      cardiac automaticity. We then analyzed our clinical experience regarding the
      location of sinus automaticity in two unique populations: those with
      inappropriate sinus tachycardia and those with a dominant pacemaker located
      outside the crista terminalis region. RESULTS: We studied 26 patients with
      inappropriate sinus tachycardia (age 34 +/- 8 years; 21 females). Non-contact
      endocardial mapping (Ensite 3000, Endocardial Solutions) was performed in 19
      patients and high-density contact mapping (Carto-3, Biosense Webster with
      PentaRay catheter) in 7 patients. The site of earliest atrial activation shifted
      after each RF application within and outside the crista terminalis region,
      indicating a wide distribution of atrial pacemaker sites. We also analyzed 11
      patients with dominant pacemakers located outside the crista terminalis (age 27
      +/- 7 years; five females). In all patients, the rhythm was the dominant
      pacemaker both at rest and during exercise and located in the right atrial
      appendage in 6 patients, in the left atrial appendage in 4 patients, and in the
      mitral annulus in 1 patient. Following ablation, earliest atrial activation
      shifted to the region of the crista terminalis at a slower rate. CONCLUSIONS:
      Membrane and sub-membrane mechanisms interact to generate cardiac automaticity.
      The present observations in patients with inappropriate sinus tachycardia and
      dominant pacemakers are consistent with a wide distribution of pacemaker sites
      within and outside the boundaries of the crista terminalis.

PMID- 30112618
TI  - [Resource allocation for treatment, research and teaching : A challenge for
      university psychiatry].

PMID- 30112619
TI  - The FUNPET-a New Hybrid Ion Funnel-Ion Carpet Atmospheric Pressure Interface for
      the Simultaneous Transmission of a Broad Mass Range.
AB  - An atmospheric pressure interface transports ions from ambient pressure to the
      low-pressure environment of a mass spectrometer. A capillary coupled to an ion
      funnel is widely used. However, conventional ion funnels do little to negate the
      large amount of energy picked up by high-mass ions from the gas flow through the
      capillary. There has been little work done on the effects of gas flow on ion
      transmission, and the previous studies have all been limited to low-mass, low
      charge ions. In this work, we account for the effects of gas flow, diffusion, and
      electric fields (static and oscillating) on ion trajectories and use simulations
      to design a new hybrid ion funnel-ion carpet (FUNPET) interface that transmits a
      broad mass range with a single set of instrument conditions. The design
      incorporates a virtual jet disruptor where pressure buildup and counter flow
      dissipate the supersonic jet that results from gas flow into the interface. This,
      and the small exit aperture that can be used with the FUNPET, reduces the gas
      flow into the next stage of differential pumping. The virtual jet disruptor
      thermalizes ions with a broad range of masses (1 kDa to 1 GDa), and once
      thermalized, they are transmitted into next region of the mass spectrometer with
      low excess kinetic energy. The FUNPET interface is easy to fabricate from
      flexible printed circuit board and a support frame made by 3D printing. The
      performance of the interface was evaluated using charge detection mass
      spectrometry. Graphical Abstract ?.

PMID- 30112620
TI  - A novel partial volume correction method for accurate quantification of [18F]
      flortaucipir in the hippocampus.
AB  - BACKGROUND: Off-target binding in the choroid plexus (CP) may cause spill-in of
      the tau PET tracer [18F] flortaucipir into the adjacent hippocampus region. The
      impact of this spill-in on hippocampal uptake was assessed using a novel partial
      volume correction method (PVC). METHODS: PVC was performed on 20 [18F]
      flortaucipir dynamic PET scans (10 probable AD and 10 controls). Volumes of
      interest (VOIs) were defined for both hippocampus and CP. The correlation between
      hippocampal and CP distribution volume (VT), with and without PVC, was
      determined. Both anatomically defined and eroded VOIs were used. RESULTS: For
      controls, the correlation between hippocampal and CP VT was significantly reduced
      after using PVC along with an eroded VOI (r2 = 0.59, slope = 0.80 versus r2 =
      0.15, slope = 0.15; difference: p < 0.05). The same was true for AD patients (p <
      0.05). CONCLUSION: PVC together with an optimized hippocampal VOI resulted in
      effective reduction of CP spill-in and improved accuracy of hippocampal VT.

PMID- 30112622
TI  - Another point of view on 2017 PRETEXT: reply to Pariente et al.

PMID- 30112623
TI  - Paediatric airway management and concerns: a survey of advanced paramedics in
      Ireland.
AB  - BACKGROUND: Paediatric airway management is of fundamental importance in the
      critically unwell child. Pre-hospital paediatric airway management especially
      endotracheal intubation is however controversial. AIM: To explore Irish Advanced
      Paramedics (APs) training, experience and clinical practice in paediatric airway
      management as well as to examine clinician attitudes toward this topic. METHODS:
      An anonymous online survey of all graduates of the University College Dublin AP
      training program (N = 453). RESULTS: With duplicates and failed email deliveries
      excluded a valid sample of 382 individuals was obtained from whom a response rate
      of 185/382 (48.4%) was achieved. Three quarters of responding APs worked in urban
      or mixed practice with the remaining minority operating primarily in rural areas.
      One quarter of responding APs reported formal training in paediatric intubation.
      Almost 70% of APs had encountered a child requiring significant airway management
      in the preceding year. However, this was a rare exposure in terms of overall
      workload. Basic airway adjuncts were used frequently in such circumstances, with
      endotracheal intubation having been attempted by only a small minority of APs.
      Lack of practice was identified by many responding APs as a key issue causing
      concern in terms of paediatric intubation. CONCLUSION: Paediatric airway
      management has key relevance for pre-hospital care in Ireland. The overall
      frequency of exposure to children who may benefit from definitive airway
      management is however likely to represent a significant barrier to the
      acquisition and maintenance of competency. The ongoing practice of pre-hospital
      paediatric intubation by APs may not justify its risks.

PMID- 30112621
TI  - Associations of sport participation with self-perception, exercise self-efficacy
      and quality of life among children and adolescents with a physical disability or
      chronic disease-a cross-sectional study.
AB  - BACKGROUND: Little evidence is available about how sports participation
      influences psychosocial health and quality of life in children and adolescents
      with a disability or chronic disease. Therefore, the aim of the current study is
      to assess the association of sports participation with psychosocial health and
      with quality of life, among children and adolescents with a disability. METHODS:
      In a cross-sectional study, 195 children and adolescents with physical
      disabilities or chronic diseases (11% cardiovascular, 5% pulmonary, 8% metabolic,
      8% musculoskeletal/orthopaedic, 52% neuromuscular and 9% immunological diseases
      and 1% with cancer), aged 10-19 years, completed questionnaires to assess sports
      participation, health-related quality of life (DCGM-37), self-perceptions and
      global self-worth (SPPC or SPPA) and exercise self-efficacy. RESULTS: Regression
      analyses showed that those who reported to participate in sports at least twice a
      week had more beneficial scores on the various indicators compared to their peers
      who did not participate in sport or less than twice a week. Those participating
      in sports scored better on all scales of the DCGM-37 scale, on the scales for
      feelings of athletic competence and children but not adolescents participating in
      sports reported greater social acceptance. Finally, we found a strong association
      between sport participation and exercise self-efficacy. CONCLUSIONS: This study
      provides the first indications that participating in sports is beneficial for
      psychosocial health among children and adolescents with a disability. However,
      more insight is needed in the direction of the relationships.

PMID- 30112625
TI  - Time-dependent pair density from the principle of minimum Fisher information.
AB  - The Euler equation for the time-dependent pair density is derived from the
      principle of minimum Fisher information. The same Euler equation is also derived
      from the recently introduced time-dependent pair density functional theory. The
      concept of steric effect to electron pairs is proposed and the steric pair energy
      is defined as the Weizsacker kinetic energy of electron pairs.

PMID- 30112624
TI  - The Use of Multi-parametric Biomarker Profiles May Increase the Accuracy of ASD
      Prediction.
AB  - Effective biomarkers are urgently needed to facilitate early diagnosis of autism
      spectrum disorder (ASD), permitting early intervention, and consequently
      improving prognosis. In this study, we evaluate the usefulness of nine biomarkers
      and their association (combination) in predicting ASD onset and development. Data
      were analyzed using multiple independent mathematical and statistical approaches
      to verify the suitability of obtained results as predictive parameters. All
      biomarkers tested appeared useful in predicting ASD, particularly vitamin E,
      glutathione-S-transferase, and dopamine. Combining biomarkers into profiles
      improved the accuracy of ASD prediction but still failed to distinguish between
      participants with severe versus mild or moderate ASD. Library-based
      identification was effective in predicting the occurrence of disease. Due to the
      small sample size and wide participant age variation in this study, we conclude
      that the use of multi-parametric biomarker profiles directly related to autism
      phenotype may help predict the disease occurrence more accurately, but studies
      using larger, more age-homogeneous populations are needed to corroborate our
      findings.

PMID- 30112626
TI  - A Population Pharmacokinetic-Pharmacodynamic Model of Pegfilgrastim.
AB  - Neutropenia and febrile neutropenia (FN) are serious side effects of cytotoxic
      chemotherapy which may be alleviated with the administration of recombinant
      granulocyte colony-stimulating factor (GCSF) derivatives, such as pegfilgrastim
      (PG) which increases absolute neutrophil count (ANC). In this work, a population
      pharmacokinetic-pharmacodynamic (PKPD) model was developed based on data obtained
      from healthy volunteers receiving multiple administrations of PG. The developed
      model was a bidirectional PKPD model, where PG stimulated the proliferation,
      maturation, and margination of neutrophils and where circulating neutrophils in
      turn increased the elimination of PG. Simulations from the developed model show
      disproportionate changes in response with changes in dose. A dose increase of 10%
      from the 6 mg therapeutic dose taken as a reference leads to area under the curve
      (AUC) increases of ~50 and ~5% for PK and PD, respectively. A full random effects
      covariate model showed that little of the parameter variability could be
      explained by sex, age, body size, and race. As a consequence, little of the
      secondary parameter variability (Cmax and AUC of PG and ANC) could be explained
      by these covariates.

PMID- 30112627
TI  - The effects of perceived chronic stress on the fMRI correlates of attentional
      control in women managers.
AB  - The aims of the current study were to examine differences in brain responses to
      cognitive control in stressed and non-stressed women managers. Stress complaints
      are highly prevalent among active workers and play an important role in women
      managers mental health and cognitive functioning. Psychosocial stress has been
      associated with differential executive functions in this population, but little
      is known about the neural correlates underlying such differences. We examined
      brain responses of a particular group of workers that has been proposed to have a
      different response to stress as a function of their status (i.e., managers).
      Stressed (n = 19) and non-stressed women managers (n = 21) were scanned using
      functional magnetic resonance imaging (fMRI) during the performance of a
      cognitively demanding task. We used the Stroop color-word task to compare neural
      activation associated with the suppression of a predominant response tendency
      (i.e., word reading) and the initiation of an appropriate behavior alternative
      (i.e., naming word color). Despite similar behavioral performances, stressed
      managers exhibited increased activation in the occipital cortex during response
      inhibition. No regions were more activated in the non-stressed relative to the
      stressed group. This finding of greater activation has been interpreted as
      compensatory brain response to maintain performance in front of cognitive
      challenge.

PMID- 30112628
TI  - Are clinical outcomes affected by type of plate used for management of mid-shaft
      clavicle fractures?
AB  - BACKGROUND: Open reduction and internal fixation (ORIF) using plate
      osteosynthesis for midshaft clavicle fractures is often complicated by the
      prominence of the implant due to the subcutaneous position of the clavicle.
      Reoperation rates for symptomatic clavicle plate removal have been reported to be
      as high as 53%. We sought to determine to which degree do clinical outcomes (all
      cause reoperation rate and rate of fracture union) differ between types of
      clavicle plates. MATERIALS AND METHODS: A retrospective chart review was
      performed using our hospital database for patients treated with ORIF for mid
      shaft clavicle fractures (OTA/AO type 15-B). Implants included in this review
      were 2.7 mm reconstruction plates, 3.5 mm reconstruction plates, 3.5 mm
      precontoured clavicle plates and 3.5 mm locking compression plates. The primary
      outcome measure was the all cause reoperation rate. Secondary outcomes compared
      the rate fracture union, documented infection, hardware failures and clinical
      symptoms at the surgical site among the various plate types. Data was collected
      and descriptive statistics were analyzed. p values < 0.05 were considered
      statistically significant. RESULTS: A total of 102 midshaft clavicle fractures
      treated with ORIF were included in this study. The majority of patients were <=
      50 years old (83.3%) and male (72.5%). The overall union rate for all plating
      constructs was 97.1%. We found that age, sex and smoking were not associated with
      the rate of re-operation. In addition, the fracture classification, type of
      implant used and number of screws used didn't increase the risk of revision
      surgery. In addition, more than 50% of patients complaining of pain at 6 weeks
      post-operatively required a second surgery for removal of hardware. Moreover,
      there was no association between age, sex, smoking, fracture classification or
      plate type and the rate of union. Interestingly, clavicle fractures fixed with
      3.5 mm reconstruction plates were more likely to have hardware failure due to
      plastic deformation, whereas 2.7 mm plates were more likely to fail by plate
      breakage. CONCLUSION: Although different types of implants have different
      biomechanical properties, no difference in reoperation, union and plate removal
      rates were found between the various plate types. Future studies with a larger
      sample size are required to further examine these outcomes. LEVEL OF EVIDENCE:
      Level III.

PMID- 30112629
TI  - Alteration of microRNA 340-5p and Arginase-1 Expression in Peripheral Blood Cells
      during Acute Ischemic Stroke.
AB  - Acute stroke alters the systemic immune response as can be observed in peripheral
      blood; however, the molecular mechanism by which microRNA (miRNA) regulates
      target gene expression in response to acute stroke is unknown. We performed a
      miRNA microarray on the peripheral blood of 10 patients with acute ischemic
      stroke and 11 control subjects. Selected miRNAs were quantified using a TaqMan
      assay. After searching for putative targets from the selected miRNAs using
      bioinformatic analysis, functional studies including binding capacity and protein
      expression of the targets of the selected miRNAs were performed. The results
      reveal a total of 30 miRNAs that were differentially expressed (16 miRNAs were
      upregulated and 14 miRNAs were downregulated) during the acute phase of stroke.
      Using prediction analysis, we found that miR-340-5p was predicted to bind to the
      3'-untranslated region of the arginase-1 (ARG1) gene; a luciferase reporter assay
      confirmed the binding of miR-340-5p to ARG1. miR-340-5p was downregulated whereas
      ARG1 mRNA was upregulated in peripheral blood in patients experiencing acute
      stroke. Overexpression of miR-340-5p in human neutrophil and mouse macrophage
      cell lines induced downregulation of the ARG1 protein. Transfection with miR-340
      5p increased nitric oxide production after LPS treatment in a mouse macrophage
      cell line. Our results suggest that several miRNAs are dynamically altered in the
      peripheral blood during the acute phase of ischemic stroke, including miR-340-5p.
      Acute stroke induces the downregulation of miR-340-5p, which subsequently
      upregulates ARG1 protein expression.

PMID- 30112630
TI  - Cytosolic Phospholipase A2 Facilitates Oligomeric Amyloid-beta Peptide
      Association with Microglia via Regulation of Membrane-Cytoskeleton Connectivity.
AB  - Cytosolic phospholipase A2 (cPLA2) mediates oligomeric amyloid-beta peptide
      (oAbeta)-induced oxidative and inflammatory responses in glial cells. Increased
      activity of cPLA2 has been implicated in the neuropathology of Alzheimer's
      disease (AD), suggesting that cPLA2 regulation of oAbeta-induced microglial
      activation may play a role in the AD pathology. We demonstrate that LPS,
      IFNgamma, and oAbeta increased phosphorylated cPLA2 (p-cPLA2) in immortalized
      mouse microglia (BV2). Abeta association with primary rat microglia and BV2
      cells, possibly via membrane-binding and/or intracellular deposition, presumably
      indicative of microglia-mediated clearance of the peptide, was reduced by
      inhibition of cPLA2. However, cPLA2 inhibition did not affect the depletion of
      this associated Abeta when cells were washed and incubated in a fresh medium
      after oAbeta treatment. Since the depletion was abrogated by NH4Cl, a lysosomal
      inhibitor, these results suggested that cPLA2 was not involved in the degradation
      of the associated Abeta. To further dissect the effects of cPLA2 on microglia
      cell membranes, atomic force microscopy (AFM) was used to determine endocytic
      activity. The force for membrane tether formation (Fmtf) is a measure of membrane
      cytoskeleton connectivity and represents a mechanical barrier to endocytic
      vesicle formation. Inhibition of cPLA2 increased Fmtf in both unstimulated BV2
      cells and cells stimulated with LPS + IFNgamma. Thus, increasing p-cPLA2 would
      decrease Fmtf, thereby increasing endocytosis. These results suggest a role of
      cPLA2 activation in facilitating oAbeta endocytosis by microglial cells through
      regulation of the membrane-cytoskeleton connectivity.

PMID- 30112631
TI  - Correction to: Adolescent Binge Alcohol Exposure Affects the Brain Function
      Through Mitochondrial Impairment.
AB  - The authors declare that the original version of this article contained a mistake
      in the data of the Figure 2, particularly in the LTP data.

PMID- 30112632
TI  - Targeting Neuroplasticity, Cardiovascular, and Cognitive-Associated Genomic
      Variants in Familial Alzheimer's Disease.
AB  - The identification of novel genetic variants contributing to the widespread in
      the age of onset (AOO) of Alzheimer's disease (AD) could aid in the prognosis
      and/or development of new therapeutic strategies focused on early interventions.
      We recruited 78 individuals with AD from the Paisa genetic isolate in Antioquia,
      Colombia. These individuals belong to the world largest multigenerational and
      extended pedigree segregating AD as a consequence of a dominant fully penetrant
      mutation in the PSEN1 gene and exhibit an AOO ranging from the early 1930s to the
      late 1970s. To shed light on the genetic underpinning that could explain the
      large spread of the age of onset (AOO) of AD, 64 single nucleotide polymorphisms
      (SNP) associated with neuroanatomical, cardiovascular, and cognitive measures in
      AD were genotyped. Standard quality control and filtering procedures were
      applied, and single- and multi-locus linear mixed-effects models were used to
      identify AOO-associated SNPs. A full two-locus interaction model was fitted to
      define how identified SNPs interact to modulate AOO. We identified two key
      epistatic interactions between the APOE*E2 allele and SNPs ASTN2-rs7852878 and
      SNTG1-rs16914781 that delay AOO by up to ~ 8 years (95% CI 3.2-12.7, P = 1.83 *
      10-3) and ~ 7.6 years (95% CI 3.3-11.8, P = 8.69 * 10-4), respectively, and
      validated our previous finding indicating that APOE*E2 delays AOO of AD in PSEN1
      E280 mutation carriers. This new evidence involving APOE*E2 as an AOO delayer
      could be used for developing precision medicine approaches and predictive
      genomics models to potentially determine AOO in individuals genetically
      predisposed to AD.

PMID- 30112633
TI  - Accuracy of portable devices in sleep apnea using oximetry-derived heart rate
      increases as a surrogate arousal marker.
AB  - PURPOSE: Type 3 home study (HS) monitors do not detect cortical arousal-related
      hypopneas and may therefore underestimate the polysomnography (PSG)-based apnea
      hypopnea index (AHI). Our aim was to test the hypothesis that scoring hypopneas
      using heart rate accelerations as a surrogate marker for cortical arousal
      (autonomic hypopnea; AnH) improves the accuracy of HS for OSA diagnosis, using
      PSG AHI as the diagnostic gold standard. METHODS: We retrospectively identified
      patients referred for OSA who underwent complete PSG following an initial
      inconclusive HS. Respiratory events were scored using AASM research (Chicago)
      criteria with additional HS scoring for AnH, defined as hypopneas based on flow
      criteria associated with an increase in pulse oximetry-derived heart rate >= 6
      beats/min. RESULTS: A total of 178 patients met inclusion criteria, with mean (+/
      SD) HS AHI = 4.4 +/- 4.2/h, which increased to 8.5 +/- 5.3/h with AnH scoring.
      The hypopnea arousal index on subsequent PSG was 7.6 +/- 7.7/h, with total AHI
      15.6 +/- 11.9/h. Bland-Altman analysis showed improved agreement between HS and
      PSG AHI (mean difference 11.2/h (95%CI 33.6, - 11.1) without vs. 7.2/h (95%CI
      29.6, - 15.4) with AnH scoring). Overall diagnostic accuracy was improved with
      AnH scoring as reflected by an increased area under the receiver-operating
      characteristic curve for AHI thresholds of 10 and 15 events/h. CONCLUSIONS: In
      this retrospective analysis, the diagnostic accuracy of type 3 HS was improved by
      the inclusion of hypopnea-associated heart rate increases as a surrogate marker
      of arousal. Prospective studies are warranted to evaluate the impact of AnH
      scoring on clinical decision-making and patient outcomes.

PMID- 30112634
TI  - Micro-CT evaluation of the cortical bone micro-architecture in the anterior and
      posterior maxilla and the maxillary sinus floor.
AB  - OBJECTIVES: To perform a within-subject comparison of the cortical bone micro
      architecture of the maxillary sinus floor (MSF) to that of the buccal aspect of
      the anterior and posterior maxilla. METHODS: Micro-CT scans of the buccal aspect
      of the anterior and posterior maxilla and of the MSF in 14 human anatomical
      specimens were recorded. Within-subject comparisons were performed for cortical
      thickness (Ct.Th) and porosity (Ct.Po), average pore volume (AvgPo.V), and pore
      density (Po.Dn). RESULTS: The MSF presented the lowest and the anterior maxilla
      the highest Ct.Th, while Ct.Po was significantly higher at the MSF compared to
      the posterior maxilla (p = 0.021). No relevant differences were recorded for
      AvgPo.V and Po.Dn among regions (p > 0.067). Further, an increased Ct.Th at the
      MSF was significantly associated with a lower Po.Dn, while a higher Ct.Th and an
      increased AvgPo.V in the anterior maxilla were associated with a higher Ct.Th and
      an increased AvgPo.V, respectively, in the posterior maxilla and MSF. Finally,
      within each region, the AvgPo.V was associated positively with Ct.Po and
      negatively with Po.Dn. CONCLUSIONS: The cortical bone of the MSF is slightly less
      thick and slightly more porous compared to the cortical bone at the buccal aspect
      of the anterior and posterior maxilla. CLINICAL RELEVANCE: During lateral and
      vertical bone augmentation procedures, the cortical recipient bone is perforated
      several times to open the bone marrow compartment to facilitate provision of
      osteoinductive cells and molecules in the augmented space. Whether it is
      meaningful to approach the MSF in a similar way during MSF augmentation
      procedures or whether the slightly more porous structure of the MSF observed
      herein reduces the cortical barrier function already sufficiently has to be
      assessed in future clinical trials.

PMID- 30112635
TI  - Brodalumab for the Treatment of Moderate-to-Severe Plaque Psoriasis: An Evidence
      Review Group Evaluation of a NICE Single Technology Appraisal.
AB  - As part of the National Institute for Health and Care Excellence single
      technology appraisal process, brodalumab was assessed to determine the clinical
      and cost effectiveness of its use in the treatment of moderate-to-severe plaque
      psoriasis. The Centre for Reviews and Dissemination and the Centre for Health
      Economics Technology Assessment Group at the University of York were commissioned
      to act as the independent Evidence Review Group. This article provides a summary
      of the Evidence Review Group's review of the company's submission, the Evidence
      Review Group report and the National Institute for Health and Care Excellence
      Appraisal Committee's subsequent guidance issued in March 2018. The main clinical
      effectiveness data were derived from three well-conducted, multicentre, double
      blind randomised controlled trials. The trials demonstrated that brodalumab
      statistically significantly reduced the severity of psoriasis and its impact on
      health-related quality of life, compared with placebo, at 12 weeks. In comparison
      with ustekinumab, statistically significantly more patients taking brodalumab had
      reduced psoriasis severity at 12 weeks. Psoriasis severity and quality of life
      also appeared improved at 52 weeks, although statistical significance was not
      assessed. Withdrawal rates were comparable to drug survival rates of other
      biological therapies and rates of adverse events were similar between brodalumab
      and ustekinumab. A network meta-analysis was presented, comparing brodalumab with
      other therapies available at the same point in the treatment pathway (i.e. in
      patients for whom standard systemic therapy or phototherapy is inadequately
      effective, not tolerated or contraindicated). The network meta-analysis ranked
      treatments in order of effectiveness, in terms of achieving different levels of
      Psoriasis Area and Severity Index response. The results indicated that brodalumab
      had a similar probability of response to ixekizumab, secukinumab and infliximab
      and a higher probability of response than ustekinumab, adalimumab, etanercept,
      apremilast, dimethyl fumarate and placebo. The company's economic model compared
      nine treatment sequences that included three lines of active therapy, consisting
      of brodalumab and other comparators recommended by the National Institute for
      Health and Care Excellence, followed by best supportive care. The sequence with
      brodalumab in the first-line position dominated sequences that started with
      adalimumab, infliximab, secukinumab and ustekinumab. The incremental cost
      effectiveness ratio of the brodalumab sequence compared to less effective and non
      dominated sequences ranged from L7145 (vs. the etanercept sequence) to L13,353
      (vs. the dimethyl fumarate sequence) per quality-adjusted life-year gained. The
      incremental cost-effectiveness ratio for the more costly and effective ixekizumab
      sequence was L894,010 per quality-adjusted life-year gained compared to the
      brodalumab sequence. At a threshold of L20,000 per quality-adjusted life-year
      gained, the brodalumab sequence had the highest probability of being cost
      effective (96%). The main limitation of the company's economic model was the
      restrictive nature of the sequences compared. Twelve separate scenarios based on
      key uncertainties were explored by the Evidence Review Group. The only scenarios
      where brodalumab was ranked lower than first were not considered to be more
      appropriate or plausible than the assumptions or scenarios included in the
      company's base case. The treatment rankings identified in the Evidence Review
      Group's alternative base case were identical to those derived from the company's
      base case model. At the first National Institute for Health and Care Excellence
      Appraisal Committee meeting, the Committee concluded that brodalumab appears to
      be as effective as other anti-interleukin-17 agents and is cost effective, based
      on the discount agreed in the patient access scheme. Brodalumab is recommended as
      an option for treating adults with severe plaque psoriasis (defined by a total
      Psoriasis Area and Severity Index score of 10 or more and a Dermatology Life
      Quality Index score of more than 10) who have not responded to other systemic non
      biological therapies. Brodalumab should be stopped at 12 weeks if the psoriasis
      has not responded adequately.

PMID- 30112636
TI  - Association between use of antidepressants or benzodiazepines and the risk of
      subsequent fracture among those aged 65+ in the Netherlands.
AB  - : This is the first study to examine the association between antidepressant and
      benzodiazepine use following a MOF and risk of subsequent fracture in those 65+.
      Using national data, drug use following MOF showed that the 1-year fully adjusted
      risk of subsequent MOF in those on antidepressants was more than doubled.
      INTRODUCTION: We evaluated the association between the use of antidepressants or
      benzodiazepines and the risk of a subsequent major osteoporotic fracture.
      METHODS: A cohort study was performed using the Dutch PHARMO Database Network.
      Between 2002 and 2011, a total of 4854 patients sustained a first major
      osteoporotic fracture after the age of 65 years, of which 1766 sustained a hip
      fracture. Incidence rates and adjusted hazard ratios were calculated using Cox
      proportional hazards models. RESULTS: Within 1 year following a major
      osteoporotic fracture, 15% (95% CI 13.7-15.7) and 31% (95% CI 30.1-32.8) of
      patients were dispensed an antidepressant or benzodiazepine, respectively.
      Current use of antidepressants in the first year following a major osteoporotic
      fracture was associated with subsequent fracture (adjusted HR 2.17 (95% CI 1.37
      3.43)). Recent and past use of antidepressants were also associated with an
      increased risk of subsequent fracture. When the complete follow-up period was
      included, only the current use of antidepressants was associated with subsequent
      fracture following a major osteoporotic fracture (adjusted HR 1.48; 95% CI 1.06
      2.06). Current benzodiazepine use was not associated with an increased risk of
      fracture within 1 year following a major osteoporotic fracture (adjusted HR 1.18;
      95% CI 0.76-1.81) or during the complete follow-up period (adjusted HR 1.18; 95%
      CI 0.90-1.55). CONCLUSION: This study provides evidence that antidepressants
      should be used with caution following a major osteoporotic fracture. It provides
      needed insights that can be used to inform clinicians when assessing subsequent
      fracture risk in patients.

PMID- 30112637
TI  - Alleged malpractice in orthopaedics. Analysis of a series of medmal insurance
      claims.
AB  - BACKGROUND: Medical malpractice is an important topic worldwide, and orthopedics
      is a clinical branch that is considered to be at a high risk for claims. The
      analysis of a series of medmal insurance claims allows forensic pathologists,
      clinicians, and insurance companies to probe the risk of a specific clinical
      branch for medical malpractice claims and highlights areas where care may be
      improved. We investigated the main features of a major Italian insurance broker's
      archive in order to identify recurrent pitfalls in this field. MATERIALS AND
      METHODS: A retrospective study was carried out on orthopedics claims. The archive
      covered claims from 2002 to 2013 that targeted 1980 orthopedists. RESULTS: 635
      claims were found and analyzed with a focus on the clinical activity invocked in
      the claim, the presence of alleged team malpractice, the clinical outcome of the
      case, and the final forensic decision regarding the claim. 299 orthopedists had
      at least one malpractice claim made against them during the available period; 146
      orthopedists were subject to more than one malpractice claim. Most of the claims
      regarded perioperative and operative cases, usually originating from civil
      litigation. The anatomical sites most commonly involved were the hip or knees,
      and sciatic nerve lesions were the main contributor. CONCLUSIONS: Orthopedics is
      a medical specialty with a high risk for malpractice claims. In our study,
      medical malpractice was observed in nearly 50% of the cases-typically in surgery
      linked cases resulting in permanent impairment of the patient. Death from
      orthopedics malpractice seemed to be rare. LEVEL OF EVIDENCE: IV.

PMID- 30112638
TI  - Impact of adjuvant chemotherapy after pancreaticoduodenectomy for distal
      cholangiocarcinoma: a propensity score analysis from a French multicentric
      cohort.
AB  - BACKGROUND: The benefit of adjuvant chemotherapy (AC) after
      pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains
      controversial. The study aimed to evaluate the impact of AC after PD for DCC in a
      large multicentric cohort. METHODS: Patients from five French centers who
      underwent from PD for DCC between 2000 and 2015 and received AC (AC+ group) or
      surgery only (AC- group) were included in the analysis. Variables associated with
      AC administration were analyzed by univariate analysis. The Cox regression
      identified covariates associated with overall survival (OS) and disease-free
      survival (DFS). The AC+ cohort was matched to the AC- cohort (1:1) by a
      propensity score (PS) based on the likelihood of AC administration and
      independent factors associated with decreased OS and DFS. RESULTS: Of the 178
      patients included, 56 (31.5%) received AC. In the whole cohort, no difference on
      OS and DFS between the AC+ and AC- groups was identified (P = 0.15 and P = 0.07,
      respectively). After PS matching, the AC+ group (n = 49) was comparable to the AC
      group (n = 49) on factors associated with AC administration and on factors
      associated with a decreased survival in the large cohort. After matching, the
      medians of OS and DFS in the AC+ group and in the AC- group were comparable
      (26.27 vs 43.33 months, P = 0.34, and 15.47 vs. 14.70 months, P = 0.79,
      respectively). CONCLUSION: Our study did not demonstrate a survival benefit of
      adjuvant chemotherapy (mostly base on gemcitabine regimen) for DCC after PD even
      after propensity score matching. New trial specially designed for DCC is urgently
      needed to improve survival after surgical resection.

PMID- 30112640
TI  - Association between alcohol dependence and both periodontal disease and tooth
      loss: a cross-sectional study.
AB  - The impact of alcohol consumption on periodontal disease and tooth loss is still
      under debate. The aim of this cross-sectional study was to evaluate the
      association between alcohol dependence and both periodontal diseases and tooth
      loss in Brazilian native Indians. Full mouth periodontal examination was
      performed and tooth loss was clinically evaluated in a representative sample of
      225 Indians (>= 19 years). Sociodemographic, oral health-related data, and
      alcohol dependence were evaluated using structured questionnaires. The subjects
      were categorized as either alcohol-dependent or non-dependent according to the
      Alcohol Use Disorders Identification Test results. Severe periodontal disease was
      defined in individuals with >= 2 proximal sites with a clinical attachment level
      >= 6 mm, not on the same tooth, and >= 1 proximal site with a probing depth >= 5
      mm. Tooth loss was categorized as one or more missing teeth, or no missing teeth.
      Bivariate models followed by logistic regression were used to assess the
      association between alcohol dependence and both periodontal disease and tooth
      loss. Prevalence ratio (PR) was calculated using Mantel-Haenszel analysis.
      Alcohol dependence increased 2.5 times the risk for tooth loss (prevalence ratio
      [PR] =2.49, 95% confidence interval [CI] = 1.01-9.04, p = 0.05). Severe
      periodontal disease was not associated with alcohol dependence (OR = 0.54, 95% CI
      = 0.22-1.31, p = 0.23). In conclusion, alcohol dependence was associated with
      tooth loss in the present population, but severe periodontal disease was not.
      Questions on alcohol dependence should be included in dental anamnesis
      questionnaires, and patients diagnosed with alcohol dependence should be referred
      for dental evaluation.

PMID- 30112639
TI  - The impact of major extended donor criteria on graft failure and patient
      mortality after liver transplantation.
AB  - INTRODUCTION: Numerous extended donor criteria (EDC) have been identified in
      liver transplantation (LT), but different EDC have different impacts on graft and
      patient survival. This study aimed to identify major EDC (maEDC) that were best
      able to predict the outcome after LT and to examine the plausibility of an
      allocation algorithm based on these criteria. METHODS: All consecutive LTs
      between 12/2006 and 03/2014 were included (n = 611). We analyzed the following
      EDC: donor age > 65 years, body mass index > 30, malignancy and drug abuse
      history, intensive care unit stay/ventilation > 7 days, aminotransferases > 3
      times normal, serum bilirubin > 3 mg/dL, serum Na+ > 165 mmol/L, positive
      hepatitis serology, biopsy-proven macrovesicular steatosis (BPS) > 40%, and cold
      ischemia time (CIT) > 14 h. We analyzed hazard risk ratios of graft failure for
      each EDC and evaluated primary non-function (PNF). In addition, we analyzed 30
      day, 90-day, 1-year, and 3-year graft survival. We established low- and high-risk
      graft (maEDC 0 vs. >= 1) and recipient (labMELD < 20 vs. >= 20) groups and
      compared the post-LT outcomes between these groups. RESULTS: BPS > 40%, donor age
      > 65 years, and CIT > 14 h (all p < 0.05) were independent predictors of graft
      failure and patient mortality and increased PNF, 30-day, 90-day, 1-year, and 3
      year graft failure rates. Three-year graft and patient survival decreased in
      recipients of >= 1 maEDC grafts (all p < 0.05) and LT of high-risk grafts into
      high-risk recipients yielded worse outcomes compared with other groups.
      CONCLUSION: Donor age > 65 years, BPS > 40%, and CIT > 14 h are major EDC that
      decrease short and 3-year graft survival, and 3-year patient survival. An
      allocation algorithm based on maEDC and labMELD is therefore plausible.

PMID- 30112642
TI  - The effect of high temperature environment on rock properties-an example of
      electromagnetic radiation characterization.
AB  - High temperature causes thermal damage to rock; the macrofracture and
      microfracture of rock can be produced under the action of temperature treatment.
      Under the influence of high temperature, the surrounding rock of deep underground
      engineering will suffer instability damage and cause serious harm to the people.
      In order to use the electromagnetic radiation (EMR) technology (a non-contact
      geophysical method) for evaluating the thermal stability of rock in underground
      thermal engineering applications, we established the EMR testing experimental
      system of rock under the action of a continuous heat source. The variation of EMR
      signals of rock under different temperatures was tested, and the EMR signals
      generates during the process of rock thermal deformation and thermal fracture,
      which were later analyzed. Under the action of a continuous heat source, the rock
      materials produced EMR signals with three kinds of frequencies. With the increase
      of rock temperature, the variation trends of EMR signals varied from the slow
      growth rate to the rapid growth rate, EMR signals can be divided into five
      stages. The increase of EMR signals is positively correlated with temperature,
      the Hurst exponent was higher than 0.7. The thermal stress was responsible for
      thermal deformation and fracture, thus generating the EMR signals. The research
      results have important guiding significance for the application of EMR technology
      to the evaluation of rock thermal stability.

PMID- 30112641
TI  - Nitrogen leaching losses following biogas slurry irrigation to purple soil of the
      Three Gorges Reservoir Area.
AB  - Ammonium (NH4+) in biogas slurries is readily nitrified into very mobile soil
      nitrate (NO3-) to promote nitrogen (N) leaching concerning which a few studies,
      however, have been reported. These slurries are regularly applied through
      irrigation to purple soil in the Three Gorges Reservoir Area, and therefore we
      explored the consequent N leaching there with a plot experiment. Biogas slurry
      irrigation was carried out with nitrogen application rates of 0, 48, 144, 240,
      336, and 480 kg N/ha. As a result, the last two rates have triggered N leaching
      being detrimental to groundwater safety. In addition, N leaching was negatively
      correlated with soil microbial biomass, diversity, and respiration, indicating a
      potential technique to prevent it with soil heterotrophs activated by increased
      ratios of carbon to nitrogen (C/N) in biogas slurries.

PMID- 30112643
TI  - Optimization in the performance and emission parameters of a DI diesel engine
      fuelled with pentanol added Calophyllum inophyllum/diesel blends using response
      surface methodology.
AB  - The primary objective of this work was to enhance the performance and emission of
      the computerized variable compression ratio (VCR) diesel engine fuelled with
      pentanol/Calophyllum inophyllum (CI)/diesel fuel blends. Based on the
      prerequisite for the current research, response surface methodology (RSM), an
      optimization technique, was adopted for the process parameters compression ratio
      (CR), load and fuel blends, and the optimized responses like brake thermal
      efficiency (BTE), brake specific fuel consumption (BSFC), oxides of nitrogen
      (NOx), carbon monoxide (CO), carbon dioxide (CO2), hydrocarbon (HC), and smoke
      were revealed with the help of Derringer's desirability approach. From the
      results, it is notified that pentanol-fuelled engine showed better performance
      and emissions at 17.5 CR, P20C20 (pentanol 20%+Calophyllum inophyllum 20%+diesel
      60%) blend and 2.5 bmep (brake mean effective pressure) load conditions. The
      observed mathematical models and validation experiments show that the VCR diesel
      engine exhibits maximum efficiency and minimum emissions at the optimized input
      parameters.

PMID- 30112644
TI  - Manganese tolerance in Verbascum olympicum Boiss. affecting elemental uptake and
      distribution: changes in nicotinic acid levels under stress conditions.
AB  - A multielemental determination methodology in conjunction with an organic acid
      analysis that were supplemented with other stress parameters and an
      ultrastructural analysis used herein to study Verbascum olympicum Boiss.
      (Scrophulariaceae) under Mn stress. Uptake and accumulation characteristics of B,
      Cu, Fe, Mn, Mo, and Zn were evaluated in 8-week-old seedlings grown in Hoagland's
      nutrient solution and exposed to 5 (CK), 50, and 200 MUM MnSO4 for 7 days.
      Hydrogen peroxide levels were determined to evaluate oxidative stress, and
      changes in compatible substance levels (total phenolic contents, glutathione and
      glutathione disulfide levels) were determined to assess antioxidant defense
      mechanisms. The distribution of manganese on the root surface was characterized
      by scanning electron microscopy images and energy-dispersive X-ray spectroscopy
      analysis. The levels of nicotinic acid, which is involved in nicotinamide adenine
      dinucleotide biosynthesis, were determined in roots and leaves to assess
      tolerance mechanisms. V. olympicum exhibited the ability to cope with oxidative
      stress originating from excessive Mn, while increased Mn concentrations were
      observed in both roots and leaves. The translocation factor of B was the most
      affected among other studied elements under the experimental conditions. Total
      nicotinic acid levels exhibited a trend of reduction in the roots and leaves,
      which could be attributed to the appropriate metabolic progress associated with
      oxidative stress based on the nicotinamide adenine dinucleotide cycle that may
      reach glutathione in response to manganese stress during plant growth.

PMID- 30112646
TI  - Multipurpose efficacy of the lyophilized cell-free supernatant of Salmonella
      bongori isolated from the freshwater fish, Devario aequipinnatus: toxicity
      against microbial pathogens and mosquito vectors.
AB  - Presently, the discovery of effective drugs and pesticides from eco-friendly
      biological sources is an important challenge in the field of life sciences. The
      present research was aimed for standardizing an innovative approach in the
      evaluation of the biological potentiality of the metabolites of fish-associated
      bacteria. We have identified 17 skin-associated bacteria from the freshwater
      fish, giant danio, Devario aquipinnatus. They were screened through biofilm
      forming and extracellular enzyme producing ability. The results of preliminary
      antibacterial evaluation of the bacterial supernatants underlined the importance
      of three potential strains (BH8, BH10 and BH11) for further applied research.
      Hence, such strains were subsequently subjected to a novel extraction procedure
      to overcome the difficulties found in polar solvents mixed with the supernatant.
      The lyophilized cell-free supernatant (LCFS) of 3 isolates were individually
      extracted by using methanol. During the testing of LCFS's methanolic extract
      (LCFS-ME) of 3 isolates, only the extract of BH11-strain exhibited potent
      inhibitory activity against the pathogenic bacteria and fungi. Furthermore, the
      larvicidal and mosquitocidal assays on the filariasis vector, Culex
      quinquefasciatus also showed its potent toxicity on both the adults and
      developmental instars of mosquito. Through molecular and phylogenetic analyses,
      the BH11 strain was identified as Salmonella bongori (KR350635). The present
      finding emphasized that the S. bongori could be an important novel source of
      effective antimicrobials and mosquitocidal agents.

PMID- 30112647
TI  - Ecological risk assessment of potentially toxic elements (PTEs) in the soil-plant
      system after reclamation of dredged sediment.
AB  - The Shayinghe River is an important tributary of the Huaihe River in China. The
      concentrations of potential toxic elements (PTEs), such as As, Hg, Pb, Cu, Zn,
      Cr, and Cd in soils and dominant vegetation from mud-dumping areas reclaimed with
      dredged sediments, and areas without mud-dumping (non-mud-dumping areas) adjacent
      to the Shayinghe River were investigated. The potential ecological risk index
      (ERI) and transfer coefficient (TC) were calculated and evaluated. The results
      showed that the potential toxic element concentrations in all sampling areas
      decreased in the order of (Zn, Cr) > (Cu, Pb) > As>Cd > Hg. Additionally, the
      total concentrations of the PTEs significantly increased from mud-dumping to the
      non-mud-dumping areas. Ecological risk assessment of soils showed that all the
      elements did not exhibit apparent ecological risks (except for As). This element
      exhibited a moderate ecological risk, implying that the dredging of sediments
      could increase the potential ecological risk of individual PTEs. Additionally,
      the PTEs in some of dominant plants in mud-dumping areas did not increase,
      indicating no apparent accumulation. The principal component analysis (PCA)
      showed that the principal components of the PTEs in plants from dredged sediments
      were different from those in the agricultural soil, indicating the influence of
      dredging on PTEs. Finally, Cd, Zn, and Hg had higher transfer coefficients (up to
      6), even if their concentrations were relatively low, suggesting potential
      ecological risks to the plants.

PMID- 30112648
TI  - Research on the ecological efficiency of the Yangtze River Delta region in China
      from the perspective of sustainable development of the economy-energy-environment
      (3E) system.
AB  - Balancing the relationship between economic development, energy utilization, and
      environmental protection has become an important task in China's Strip Planning
      and Construction. This article takes the annual panel data from 2005 to 2015 as
      the research object firmly grasps the research basis of the Economy-Energy
      Environment (3E) System, and focuses on building a new research framework from
      both internal and external perspectives of the eco-efficiency index to achieve
      the exploratory research on regional ecological efficiency changes and
      influencing factors. First of all, it uses super-efficient slacks-based measure
      (SBM) model which introduces undesired outputs to measure eco-efficiency at
      different levels. Then, it applies Malmquist index to calculate total factor
      productivity and structural efficiencies. Finally, it selects six indicators and
      uses the STIRPAT regression model to analyze external factors. The results
      indicate that (1) the overall ecological efficiency is effective and maintaining
      a good momentum of development. Among all the cities and provinces, Shanghai and
      Zhejiang provinces play the role of "stabilizers," while Jiangsu and Anhui
      provinces act as "accelerators." (2) All 41 prefecture-level cities can be
      divided into four different types, i.e., "high-high", "low-high", "low-low," and
      "high-low" cities, and there is an obvious phenomenon of spatial clustering; (3)
      pure technical efficiency and scale efficiency is the core driving force for the
      improvement of ecological efficiency. (4) Anhui and Jiangsu provinces show a U
      shaped relationship, while Zhejiang province shows an inverted U-shaped
      relationship. Graphical abstract The structure of introduction-body paragraphs
      conclusion carbon.

PMID- 30112645
TI  - Encapsulation of cinnamon essential oil in whey protein enhances the protective
      effect against single or combined sub-chronic toxicity of fumonisin B1 and/or
      aflatoxin B1 in rats.
AB  - Fumonisin B1 (FB1) and aflatoxin B1 (AFB1) are fungal metabolites that frequently
      co-occur in foodstuffs and are responsible for mycotoxicosis and several primary
      cancers. Cinnamon essential oil (CEO) has a spacious range of benefit effects but
      also has some limitations owing to its strong taste or its interaction with some
      drugs. This study aimed to use the cinnamon oil emulsion droplets (COED) for the
      protection against oxidative stress, cytotoxicity, and reproductive toxicity in
      male Sprague-Dawley rats sub-chronically exposed to FB1 and/or AFB1. The
      composition of CEO was identified using GC-MS then was encapsulated using whey
      protein as wall material. Male rats were divided into eight groups and treated
      orally for 8 weeks as follows: control group, AFB1-trreated group (80 MUg/kg
      b.w), FB1-treated group (100 mg/kg b.w), FB1 plus AFB1-treated group, and the
      groups treated with COED plus FB1 and/or AFB1. Blood and samples of the kidney,
      liver, and testis were collected for different analysis and histopathological
      examination. The GC-MS analysis revealed that cinnamaldehyde, alpha-copaene,
      trans-cinnamaldehyde, caryophyllene, and delta-cadinene were the main compounds
      in COE. The average size of COED was 235 +/- 1.4 nm and the zeta potential was -
      6.24 +/- 0.56. Treatment with FB1 and/or AFB1 induced significant disturbances in
      the serum biochemical analysis, oxidative stress parameters, DNA fragmentation,
      gene expression, and testosterone and severe pathological changes in the tested
      organs. Moreover, treatment with both mycotoxins induced synergistic toxic
      effects. COED did not induce toxic effects and could normalize the majority of
      the tested parameters and improve the histological picture in rats treated with
      FB1 and/or AFB1. It could be concluded that COED induce potential protective
      effects against the single or combined exposure to FB1 and AFB1.

PMID- 30112649
TI  - Imaging of growth factors on a human tooth root canal by surface-enhanced Raman
      spectroscopy.
AB  - Endodontic treatment of immature permanent teeth with necrotic pulp poses several
      clinical challenges and is one of the most demanding interventions in
      endodontics. Recently, with new discoveries in the field of tissue engineering,
      novel treatment protocols have been established. The most promising treatment
      modality is revascularization, whose integral part is the exposure of collagen
      matrix and embedded growth factors. However, optimization of the treatment
      protocol requires a development of analytical procedures able to analyze growth
      factors directly on the sample surface. In this work, method based on surface
      enhanced Raman spectroscopy (SERS) was developed to investigate the influence of
      the time of the medical treatment using EDTA on exposure and accessibility of the
      growth factors, namely TGF-beta1, BMP-2, and bFGF on the dentine surface. The
      nanotags, which consist of magnetic Fe3O4@Ag nanocomposite covalently
      functionalized by tagged antibodies (anti-TGF-beta1-Cy3, anti-BMP-2-Cy5, and anti
      bFGF-Cy7), were employed as a SERS substrate. Each antibody was coupled with a
      unique label allowing us to perform a parallel analysis of all three growth
      factors within one analytical run. Developed methodology presents an interesting
      alternative to a fluorescence microscopy and in contrary allows evaluating a
      chemical composition and thus minimizing possible false-positive results.
      Graphical abstract.

PMID- 30112650
TI  - Ten-year trends in intensive care admissions for respiratory infections in the
      elderly.
AB  - BACKGROUND: The consequences of the ageing population concerning ICU
      hospitalisation need to be adequately described. We believe that this discussion
      should be disease specific. A focus on respiratory infections is of particular
      interest, because it is strongly associated with old age. Our objective was to
      assess trends in demographics over a decade among elderly patients admitted to
      the ICU for acute respiratory infections. METHODS: A cross-sectional study was
      performed between 2006 and 2015 based on hospital discharge databases in one
      French region (2.5 million inhabitants). Patients with acute respiratory
      infection were selected according to the specific ICD-10 diagnosis codes
      recorded, including acute exacerbation of chronic obstructive pulmonary disease
      (AECOPD) and community-acquired pneumonia (CAP). We also identified comorbid
      conditions based on any significant ICD-10 secondary diagnoses adapted from the
      Charlson and Elixhauser indexes. RESULTS: A total of 98,381 hospital stays for
      acute respiratory infection were identified among the 3,856,785 stays over the 10
      year period. The number of patients 75 y/o and younger increased 1.6-fold from
      2006 to 2015, whereas the numbers of patients aged 85-89 and >= 90 y/o increased
      by 2.5- and 2.1-fold, respectively. Both CAP and AECOPD hospitalisations
      significantly increased for all age groups over the decade. ICU hospitalisations
      for respiratory infection increased 2.7-fold from 2006 to 2015 (p = 0.0002). The
      greatest increases in the use of ICU resources were for the 85-89 and >= 90 y/o
      groups, which corresponded to increases of 3.3- and 5.8-fold. Indeed, the
      proportion of patients hospitalized for respiratory infection in ICU that were
      elderly clearly grew during the decade: 11.3% were >= 85 y/o in 2006 versus 16.4%
      in 2015 (p < 0.0001). This increase in ICU hospitalisation rate of ageing
      patients was not associated with significant changes in the level of care or ICU
      mortality except for patients >= 90 y/o (for whom ICU mortality dropped from 40.9
      to 22.3%, p = 0.03). CONCLUSION: We observed a substantial increase in acute
      respiratory infection diagnoses associated with hospitalisation between 2006 and
      2015, with a growing demand for critical care services. Both the absolute number
      and the percentage of elderly patient ICU admissions increased over the last
      decade, with the greatest increases being observed for patients 85 years and
      older.

PMID- 30112653
TI  - Recurrent kidney stones in a child with Lesch-Nyhan syndrome: Questions.

PMID- 30112652
TI  - Inpatient Glycemic Management in the Setting of Renal
      Insufficiency/Failure/Dialysis.
AB  - PURPOSE OF THIS REVIEW: Chronic diabetic nephropathy and renal dysfunction from
      other causes are common in hospitalized patients with diabetes. Available
      diabetes management guidelines aim to reduce hyperglycemia and hypoglycemia, both
      independent risk factors for hospital outcomes. Renal dysfunction, which
      increases the risk of hypoglycemia, adds a layer of complexity in diabetes
      management. Therefore, modified glucose goals and treatment regimens may be
      required. RECENT FINDINGS: Recent prospective and retrospective studies provide
      direction on safe insulin therapy for diabetes inpatients with renal compromise.
      Studies of newer diabetes pharmacotherapy provide data on oral agent use in the
      inpatient setting. Diabetes therapy should be modified with changing renal
      function. Glucose management in patients on peritoneal or hemodialysis is
      challenging. Reducing weight-based doses of insulin and use of newer insulins can
      reduce hypoglycemia risk. Safety and efficacy of DPP-4 inhibitors has been
      evaluated in the hospital and nursing home setting. Metformin, SGLT-2 inhibitors,
      and GLP1 receptor agonists can be used in several stages of renal dysfunction
      prior to and at discharge.

PMID- 30112654
TI  - Hemodynamic impact of the connection to continuous renal replacement therapy in
      critically ill children.
AB  - BACKGROUND: Continuous renal replacement therapy (CRRT) is the treatment of
      choice for critically ill children with acute kidney injury. Hypotension after
      starting CRRT is frequent but very few studies have analyzed its incidence and
      clinical relevance. METHODS: A prospective, observational study was performed
      including critically ill children treated with CRRT between 2010 and 2014.
      Hemodynamic data and connection characteristics were collected before, during,
      and 60 min after CRRT circuit connection. Hypotension with the connection was
      defined as a decrease in > 20% of the mean arterial pressure from baseline or
      when intravenous fluid resuscitation or an increase in vasopressors was required.
      RESULTS: One hundred sixty-one connections in 36 children (median age 18.8
      months) were analyzed. Twenty-eight patients (77.8%) were in the postoperative
      period of cardiac surgery, 94% had mechanical ventilation, and 86.1% had
      vasopressors. The heparinized circuit priming solution was discarded in 8.7% and
      infused to the patient in 18% of the connections. The circuit was re-primed in
      the remaining 73.3% using albumin (79.3%), red blood cells (4.5%), or another
      crystalloid solution without heparin (16.2%). Hypotension occurred in 49.7% of
      the connections a median of 5 min after the beginning of the therapy. Fluid
      resuscitation was required in 38.5% and the dose of vasopressors was increased in
      12.4% of the connections. There was no relationship between hypotension and age
      or weight. Re-priming the circuit with albumin reduced the incidence of
      hypotension from 71.4 to 44.6% (p = 0.004). CONCLUSIONS: Hypotension after the
      connection to CRRT is very frequent in critically ill children. Re-priming the
      circuit with albumin could improve hemodynamics during connection.

PMID- 30112657
TI  - Recurrent kidney stones in a child with Lesch-Nyhan syndrome: Answers.

PMID- 30112656
TI  - Should ACE inhibitors and ARBs be used in combination in children?
AB  - The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in a host of
      renal and cardiovascular functions. Angiotensin-converting enzyme inhibitors
      (ACEIs) and angiotensin receptor blockers (ARBs), drugs that disrupt RAAS
      function, are effective in treating hypertension and offer other renoprotective
      effects independent of blood pressure (BP) reduction. As our understanding of
      RAAS physiology and the feedback mechanisms of ACE inhibition and angiotensin
      receptor blockade have improved, questions have been raised as to whether
      combination ACEI/ARB therapy is warranted in certain patients with incomplete
      angiotensin blockade on one agent. In this review, we discuss the rationale for
      combination ACEI/ARB therapy and summarize the results of key adult studies and
      the limited pediatric literature that have investigated this therapeutic
      approach. We additionally review novel therapies that have been developed over
      the past decade as alternative approaches to combination ACEI/ARB therapy, or
      that may be potentially used in combination with ACEIs or ARBs, in which further
      adult and pediatric studies are needed.

PMID- 30112658
TI  - Iron, Zinc, and Physical Performance.
AB  - Iron and zinc are nutritionally essential trace elements that function through
      incorporation into proteins and enzymes; many of these proteins and enzymes
      affect physical performance. Poor iron status (iron deficiency and iron
      deficiency anemia) is prevalent in both developed and developing nations. Zinc
      deficiency has been reported in clinical and population studies, although the
      incidence is difficult to quantify due to the lack of a reliable zinc status
      indicator. The objective of this manuscript is to review the relationship between
      iron and zinc status and physical performance. In sum, numerous reports indicate
      diminished physical performance in individuals with poor iron and/or zinc status,
      whereas, in individuals with adequate status, evidence supporting a beneficial
      role of iron or zinc at levels beyond the recommended dietary allowance for
      optimizing physical performance is lacking.

PMID- 30112655
TI  - Renal function and blood pressure are altered in adolescents born preterm.
AB  - BACKGROUND: Preterm birth increases the risk of hypertension and kidney disease.
      However, it is unclear when changes in blood pressure (BP) and renal function
      become apparent and what role obesity and sex play. We hypothesized adolescents
      born preterm have higher BP and worse kidney function compared to term in an
      obesity- and sex-dependent manner. METHODS: Cross-sectional analysis of 14-year
      olds born preterm with very low birth weight (n = 96) compared to term (n = 43).
      We used generalized linear models to estimate the associations among preterm
      birth and BP, estimated glomerular filtration rate (eGFR), and ln (x) urinary
      albumin-to-creatinine ratio (ACR), stratified by overweight/obesity (OWO, body
      mass index (BMI) >= 85th percentile) and sex. RESULTS: Compared to term, preterm
      born adolescents had higher systolic blood pressure (SBP) and diastolic blood
      pressure (DBP) (adjusted beta (abeta) 3.5 mmHg, 95% CI - 0.1 to 7.2 and 3.6 mmHg,
      95% CI 0.1 to 7.0), lower eGFR (beta - 8.2 mL/min/1.73 m2, 95% CI - 15.9 to -
      0.4), and higher ACR (abeta 0.34, 95% CI - 0.04 to 0.72). OWO modified the
      preterm-term difference in DBP (BMI < 85th percentile abeta 5.0 mmHg, 95% CI 0.7
      to 9.2 vs. OWO 0.2 mmHg, 95% CI - 5.3 to 5.6) and ACR (OWO abeta 0.72, 95% CI
      0.15 to 1.29 vs. BMI < 85th percentile 0.17, 95% CI - 0.31 to 0.65). Sex modified
      the preterm-term ACR difference (female abeta 0.52, 95% CI 0.001 to 1.04 vs. male
      0.18, 95% CI - 0.36 to 0.72). CONCLUSIONS: Prematurity was associated with higher
      BP and reduced renal function that were detectable in adolescence. OWO and sex
      may modify the strength of these relationships.

PMID- 30112659
TI  - Biochemical and Morphological Alterations in Hearts of Copper-Deficient Bovines.
AB  - Copper deficiency is an important disease of cattle that produces several
      clinical signs and lesions, due to alterations in copper-dependent enzymes. One
      of the organs affected by this deficiency is the heart (falling disease), but
      nevertheless, these cardiac lesions have not been extensively studied in bovines.
      The aim of this work was to propose a possible pathogenic mechanism for cardiac
      lesions in cattle affected by copper deficiency. Because of the possible
      existence of oxidative distress caused by low levels of copper-zinc-superoxide
      dismutase and cytochrome oxidase, ultrastructural and histological lesions have
      been evaluated in the heart of bovines in which a Cu deficiency had been induced
      using high molybdenum and sulfur levels in the diet. Our results indicated that
      copper deficiency produces significant damage in myocardium with high levels of
      lipid oxidation and a significant reduction in copper-zinc-superoxide dismutase
      activity leading to an oxidative distress situation. However, cytochrome oxidase
      activity was not significantly reduced. Histological observation revealed a
      significant increase in the amount of connective tissue, enlarged basement
      membranes of myocytes, and numerous Anichkov cells, in the hearts of deficient
      animals. Ultrastructural observation showed a significant enhancement in the
      mitochondrial volume density, with presence of lesions such as swelling and
      cristae disruption. We conclude that copper deficiency in bovines causes
      morphological lesions in the heart due to an oxidative damage produced by copper
      dependent enzyme alterations.

PMID- 30112660
TI  - A luciferase complementation assay system using transferable mouse artificial
      chromosomes to monitor protein-protein interactions mediated by G protein-coupled
      receptors.
AB  - G protein-coupled receptors (GPCRs) are seven-transmembrane domain receptors that
      interact with the beta-arrestin family, particularly beta-arrestin 1 (ARRB1).
      GPCRs interact with 33% of small molecule drugs. Ligand screening is promising
      for drug discovery concerning GPCR-related diseases. Luciferase complementation
      assay (LCA) enables detection of protein-protein complementation via
      bioluminescence following complementation of N- and C-terminal luciferase
      fragments (NEluc and CEluc) fused to target proteins, but it is necessary to co
      express the two genes. Here, we developed LCAs with mouse artificial chromosomes
      (MACs) that have unique characteristics such as stable maintenance and a
      substantial insert-carrying capacity. First, an NEluc-ARRB1 was inserted into
      MAC4 by Cre-loxP recombination in CHO cells, named ARRB1-MAC4. Second, a
      parathyroid hormone receptor 2 (PTHR2)-CEluc or prostaglandin EP4 receptor (hEP4)
      CEluc were inserted into ARRB1-MAC4, named ARRB1-PTHR2-MAC4 and ARRB1-hEP4-MAC4,
      respectively, via the sequential integration of multiple vectors (SIM) system.
      Each MAC was transferred into HEK293 cells by microcell-mediated chromosome
      transfer (MMCT). LCAs using the established HEK293 cell lines resulted in 35,000
      photon counts upon somatostatin stimulation for ARRB1-MAC4 with transient
      transfection of the somatostatin receptor 2 (SSTR2) expression vector, 1800
      photon counts upon parathyroid hormone stimulation for ARRB1-PTHR2-MAC4, and
      35,000 photon counts upon prostaglandin E2 stimulation for ARRB1-hEP4-MAC4. These
      MACs were maintained independently from host chromosomes in CHO and HEK293 cells.
      HEK293 cells containing ARRB1-PTHR2-MAC4 showed a stable reaction for long-term.
      Thus, the combination of gene loading by the SIM system into a MAC and an LCA
      targeting GPCRs provides a novel and useful platform to discover drugs for GPCR
      related diseases.

PMID- 30112661
TI  - Analysis and assessment of heavy metals in soils around the industrial areas in
      Mettur, Tamilnadu, India.
AB  - Industrialization and extraction of natural resources have resulted in large
      scale environmental contamination and pollution. We have collected the soil
      samples from five different industrial areas of Mettur (Chemplast Sanmar Limited,
      SIDCO-1, SIDCO-2, SIDCO-3, thermal power plant), Salem district, Tamil Nadu,
      India, and estimated the physical properties (pH, EC, and alkalinity), chemical
      properties (major and minor elements), and heavy metal analysis. Thermal power
      plant soil sample showed higher pH 5.01, EC 29.33 MUmhos/cm compared with rest of
      the samples. Acidic nature of the soil samples near thermal power plant was due
      to the effect of ash disposal. The high electrical conductivity is due to the
      disposal of soluble electrolytes and deposition of dust particles released from
      Thermal Power Plant. Alkalinity of the SIDCO-2 soil (410 ppm) was higher than
      that of rest of the soil samples. Soil samples show higher concentrations of
      chloride (10,400 ppm) from thermal power plant when compared with soil sample
      collected from all 15 sample areas. It was found that heavy metal concentrations
      lie in the following ranges: Cu (3.780-86.360 ppm) > Pb (0.018-1.710 ppm) > As
      (0.053-0.342 ppm) in Mettur area. The maximum concentration of copper (Cu) found
      in SIDCO-1 (86.360 ppm) was due to electroplating industry, smelting and
      refining, mining, and biosolids. Maximum concentrations of arsenic (As) recorded
      (0.342 ppm) in thermal Power plant was due to ash disposal from the coal-fired
      thermal power plant. And maximum concentrations of lead (Pb) (1.710 ppm) in
      Chemplast area are due to the effluent discharge of manufacturing units like PVC
      resins, chlorochemicals, and piping systems in Chemplast which are main source of
      heavy metal pollutants. Therefore, major mining and smelting of metalliferous
      ores, burning of leaded gasoline, municipal sewage, industrial wastes enriched
      with Pb, and paints, which exceeded WHO (2011) and BIS (2003) recommended
      standard for lead (0.090 ppm) and arsenic (0.010 ppm). The geo-accumulation index
      (Igeo) study indicates that there is no significant contamination with lead and
      arsenic but there is a moderate contamination with copper (86.360 ppm). According
      to the calculated values of PLI, area 1 (0.061) has been contaminated high
      compared with other areas.

PMID- 30112662
TI  - Collective behavior of Vicsek particles without and with obstacles?.
AB  - In our work we have studied a two-dimensional suspension of finite-size Vicsek
      hard disks, whose time evolution follows an event-driven dynamics between
      subsequent time steps. Having compared its collective behaviour with the one
      expected for a system of scalar Vicsek point-like particles, we have analysed the
      effect of considering two possible bouncing rules between the disks: a Vicsek
      like rule and a pseudo-elastic one, focusing on the order-disorder transition.
      Next, we have added to the two-dimensional suspension of hard-disk Vicsek
      particles disk-like passive obstacles of two types: either fixed in space or
      moving according to the same event-driven dynamics. We have performed a detailed
      analysis of the particles' collective behaviour observed for both fixed and
      moving obstacles. In the fixed obstacles case, we have observed formation of
      clusters at low noise, in agreement with previous studies. When using moving
      passive obstacles, we found that that order of active particles is better
      destroyed as the drag of obstacles increases. In the no drag limit an interesting
      result was found: introduction of low drag passive particles can lead in some
      cases to a more ordered state of active flocking particles than what they show in
      bulk.

PMID- 30112663
TI  - Peptide binding to cleaved CD31 dampens ischemia/reperfusion-induced intestinal
      injury.
AB  - BACKGROUND: CD31 is a key transmembrane neutrophil immunoregulatory receptor.
      Mesenteric ischemia/reperfusion-induced neutrophil activation leads to a massive
      cleavage and shedding of the most extracellular domains of CD31 into plasma,
      enhancing the deleterious effect of neutrophil activation. We have evaluated the
      preventive therapeutic potential of an engineered synthetic octapeptide (P8RI),
      which restores the inhibitory intracellular signaling of cleaved CD31, in an
      experimental model of acute mesenteric ischemia/reperfusion. METHODS: In a
      randomized, controlled, and experimenter-blinded preclinical study, mesenteric
      ischemia/reperfusion (I/R) was induced in Wistar rats by superior mesenteric
      artery occlusion for 30 min followed by 4 h of reperfusion. Three groups of rats
      were compared: I/R + saline perfusion (I/R controls group, n = 7), I/R +
      preventive P8RI perfusion (P8RI group, n = 7), and sham-operated rats + saline
      perfusion (sham group, n = 7). RESULTS: Compared with I/R controls, P8RI
      perfusion significantly decreased intestinal ischemia/reperfusion injury (Chiu's
      score, P = 0.01; epithelial area, P = 0.001) and bacterial translocation (plasma
      Escherichia coli DNA, P = 0.04) and could limit intestinal bleeding (P = 0.09).
      P8RI decreased neutrophil activation assessed by matrix metalloproteinase-9
      release in plasma (P < 0.001) and in the intestinal wall, albeit without
      statistical significance (P = 0.06 and P = 0.058 for myeloperoxydase). Inhibition
      of CD31 cleavage from neutrophils could play a major role in the protective
      effects of P8RI (P < 0.0001). CONCLUSIONS: Preventive administration of P8RI, a
      CD31-agonist peptide, could decrease I/R-induced intestinal injury by potentially
      limiting neutrophil activation.

PMID- 30112664
TI  - Protective loop ileostomy increases the risk for prolonged postoperative
      paralytic ileus after open oncologic rectal resection.
AB  - PURPOSE: Postoperative gut dysmotility is a physiologic and frequent temporary
      reaction after major abdominal surgery. If paralysis merges into a prolonged
      ileus state, it causes significant morbidity and subsequently worse outcome and
      discomfort for the patients. Pathophysiology of pathologic prolonged
      postoperative paralytic ileus remains multifactorial. METHODS: We present a
      retrospective single-center analysis of patients, who underwent a primary open
      oncologic anterior rectal resection with primary anastomosis with or without
      defunctioning loop ileostomy during a 43-month period of observation. Primary
      endpoint was the rate of prolonged postoperative paralytic ileus, defined by the
      intravenous administration of neostigmine. Confounders for regression analysis
      were assessed by univariate analysis and correlations between confounders were
      examined. Odds ratio for prolonged postoperative paralytic ileus in patients with
      defunctioning loop ileostomy was estimated by a logistic regression model.
      RESULTS: Of 101 patients (62 male), 62 (61.39%) received defunctioning loop
      ileostomy. In univariate analysis, male gender and patients with ileostomy showed
      more frequently prolonged paralysis by tendency (both p = 0.07). Logistic
      regression analysis proves the influence of a defunctioning ileostomy on the
      development of prolonged postoperative paralytic ileus after oncologic rectal
      resection (p = 0.047). Odds ratio for prolonged postoperative paralytic ileus in
      patients with ileostomy was 4.96 [95% CI 1.02-24.03]. CONCLUSIONS: Although the
      construction of defunctioning loop ileostomies during rectal resection is a safe,
      uncomplicated surgical procedure, they can cause significant postoperative
      morbidity for the patients. High fluid and electrolyte loss are well-known
      complications, but herewith we raise the evidence for prolonged gut paralysis in
      patients with defunctioning loop ileostomy.

PMID- 30112665
TI  - Natural history of intraventricular meningiomas: systematic review.
AB  - Review the data published on the subject to create a more comprehensive natural
      history of intraventricular meningiomas (IVMs). A Medline search up to March 2018
      using "intraventricular meningioma" returned 98 papers. As a first selection
      step, we adopted the following inclusion criteria: series and case reports about
      IVMs, as well as papers written in other languages, but abstracts written in
      English were evaluated. Six hundred eighty-one tumors were evaluated from 98
      papers. The majority of the tumors were located in the lateral ventricles (602
      88.4%), fourth ventricle (59-8.7%), and third ventricle (20-2.9%). These tumors
      accounted for a mortality rate of 4.0% (25 deaths) and a recurrence rate of 5.3%
      (26 recurrences). The majority of the tumors were grade I (89.8%) and consisted
      of the following subtypes: fibrous, 39.7% (n = 171); transitional, 22.0% (n =
      95); meningothelial, 18.6% (n = 80); angiomatosus, 3.2% (n = 14); psammomatous,
      2.6% (n = 11); and others, 13.9% (n = 60). Forty-five patients (7.4%) presented
      with grade II (GII) tumors, and 17 patients (2.8%) presented with grade III
      (GIII) tumors. These tumors follow the histopathological distribution of
      meningiomas in general, with the exception of the higher prevalence of the
      fibrous subtype, possibly due to its embryonic origin. Recurrence and mortality
      were lower than in other localizations likely due to a complete surgical
      resection rate than in the convexity and skull base, which suggests that GTR is
      the gold standard for the management of IVMs.

PMID- 30112666
TI  - Lay Perspectives on Receiving Different Types of Genomic Secondary Findings: a
      Qualitative Vignette Study.
AB  - Genome-wide sequencing may generate secondary findings (SFs). It is recommended
      that validated, clinically actionable SFs are reported back to patients/research
      participants. To explore publics' perspectives on the best ways to do this, we
      performed a vignette study among Finnish adults. Our aim was to explore how lay
      people react to different types of hypothetical genomic SFs. Participants
      received a hypothetical letter revealing a SF predisposing to a severe but
      actionable disease-cardiovascular disease (familial hypercholesterolemia, long QT
      syndrome) or cancer (Lynch syndrome, Li-Fraumeni syndrome). Participants (N = 29)
      wrote down their initial reactions, and discussed (N = 23) these in focus groups.
      Data were analyzed using inductive thematic analysis. Reactions to hypothetical
      SFs varied according to perceived severity and familiarity of the diseases. SFs
      for cancer were perceived as more threatening than for cardiovascular diseases,
      but less distressing than risk for psychiatric or neurological disorders, which
      participants spontaneously brought up. Illness severity in terms of lived
      experience, availability of treatment, stigma, and individual's responsibility to
      control risk were perceived to vary across these disease types. In addition to
      clinical validity and utility, SF reporting practices need to take into account
      potential familiarity and lay illness representations of different diseases.
      Illness representations may influence willingness to receive SFs, and
      individuals' reactions to this information.

PMID- 30112667
TI  - Cigarette smoking associates inversely with a cluster of two autoimmune diseases:
      ulcerative colitis and pemphigus.

PMID- 30112668
TI  - Acquired drug-induced long QTc: new insights coming from a retrospective study.
AB  - INTRODUCTION: Several drug classes (antiarrhythmics, antimicrobials,
      antidepressants, phenothiazines, opiates, prokinetics of digestive tract, etc.)
      have been related to ventricular hyperkinetic arrhythmias such as torsade de
      pointes (TdP). TdPs are usually heralded by an abnormal prolongation of heart
      rate-corrected QT interval on the electrocardiogram, so-called drug-induced long
      heart rate-corrected QT (diLQTc). We do not know to what extent the drug-induced
      QTc prolongation is able to predict malignant arrhythmias. Thus, we have
      retrospectively examined the clinical history of patients with diLQTc. METHODS:
      The case record, concerning the period January 2008-December 2017, was collected
      from two hospitals. diLQTc was defined as drug-induced heart rate-corrected QT of
      >= 450 ms or >= 470 ms, respectively in male or female patients. The primary
      purpose was to verify whether in diLQTc patients the length of this
      electrocardiographic segment was associated with the risk of symptoms or events
      (TdP, ventricular fibrillation). RESULTS: Seventy-three validated cases of diLQTc
      were gathered. Among them, the QTc duration was not able to predict the
      occurrence of symptoms or events (odds ratio, 0.998; 95% CI, 0.984 to 1.013; p =
      0.8821). Likewise, a diQTc lasting longer than 500 ms compared to diQTc comprised
      between 450 and 500 ms was not associated with an increased risk of arrhythmic
      events. CONCLUSIONS: In our diLQTc patients, QTc duration did not predict
      occurrence of symptoms, or arrhythmic events. Thus, other determinants should be
      postulated to clarify why sometimes diQTc prolongation propitiates ventricular
      malignant arrhythmias whereas in other cases this arrhythmogenic effect is
      lacking.

PMID- 30112669
TI  - Early prediction of acute kidney injury in children: known biomarkers but novel
      combination.

PMID- 30112670
TI  - Attention and anticipation in response to varying levels of uncertain threat: An
      ERP study.
AB  - Individual differences in responding to uncertainty have been proposed as a key
      mechanism of how anxiety disorders develop and are maintained. However, most
      empirical work has compared responding to uncertain versus certain threat
      dichotomously. This is a significant limitation because uncertainty in daily life
      occurs along a continuum of probability, ranging from very low to high chances of
      negative outcomes. The current study investigated (1) how varying levels of
      uncertainty impact attention and anticipatory emotion, and (2) how these effects
      are moderated by individual differences in risk factors for anxiety disorders,
      particularly intolerance of uncertainty (IU) and worry. Participants (n = 65)
      completed a card task in which the probability of shock varied across trials. Two
      event-related potential components were examined: the P2, an index of attention,
      and the stimulus-preceding negativity (SPN), an index of anticipation. The P2
      tracked the level of uncertainty and was smaller for more uncertain outcomes.
      Participants higher in IU exhibited greater differences in the P2 across levels
      of uncertainty. The SPN did not track specific levels of uncertainty but was
      largest for uncertain threat compared with certain threat and safety. Greater
      worry was associated with blunting of the SPN in anticipation of all outcomes.
      Thus, attention appears to be sensitive to variations in uncertainty, whereas
      anticipation seems sensitive to uncertainty globally. The two processes appear to
      be distinctly related to anxiety risk factors. These results highlight the value
      of examining multiple aspects of anticipatory responding to varying levels of
      uncertainty for understanding risk for anxiety disorders.

PMID- 30112672
TI  - Long-term effects of multi-walled carbon nanotubes on the performance and
      microbial community structures of an anaerobic granular sludge system.
AB  - Multi-walled carbon nanotubes (MWCNTs) released into the sewage may cause
      negative and/or positive effects on the treatment system. The objective of this
      study was to explore over 110 days' effect of MWCNTs on the performance of
      anaerobic granular sludge and microbial community structures in an upflow
      anaerobic sludge blanket (UASB) reactor. The results showed that MWCNTs had no
      significant effect on the removal of chemical oxidation demand (COD) and ammonia
      in UASB reactor, but the total phosphorus (TP) removal efficiency increased by
      29.34%. The biogas production of the reactor did not change. The anaerobic
      granular sludge tended to excrete more EPS to resist the effects of MWCNTs during
      the long-term impact. Illumina MiSeq sequencing of 16S rRNA gene revealed that
      MWCNTs did not affect the microbial diversity, but altered the composition and
      structure of microbial community in the reactor. In this process,
      Saccharibacteria replaced Proteobacteria as the highest abundant bacterial
      phylum. MWCNTs promoted the differentiation of methanogen structure, resulting in
      increase of Methanomassiliicoccus, Methanoculleus, and the uncultured WCHA1-57.
      These results indicated that MWCNTs impacted the performance of UASB reactor and
      the structures of the microbial community in anaerobic granular sludge.

PMID- 30112673
TI  - Clinical Manifestation of Hyper IgE Syndrome Including Otitis Media.
AB  - PURPOSE OF REVIEW: The hyper IgE syndromes (HIES) comprise a group of rare
      primary immunodeficiency disorders (PIDDs), which are characterized by extremely
      high serum IgE levels, eczema, recurrent skin and pulmonary infections. Both
      autosomal dominant (AD) HIES due to STAT3 mutations and autosomal recessive (AR)
      HIES due to PGM3, SPINK5, DOCK8 and TKY2 mutations have been reported. Here, we
      aim to summarize and compare the major clinical manifestations of different
      subtypes of HIES. We will also discuss otitis media, which usually do not get
      enough attention in HIES. Update and familiarity with these clinical features
      will help to make a better diagnose, assessment and treatment of HIES. RECENT
      FINDINGS: Although hyper serum IgE levels have been identified in PGM3 deficiency
      and Comel-Netherton syndrome, PGM3 and SPINK5 genes were not included in the list
      of genetic etiologies of AR-HIES by the Expert Committee of the International
      Union of Immunological Societies until 2015. The identification of these HIES
      causing genes greatly promoted the pathogenic mechanism studies of HIES. Also, in
      recent years, more clinical manifestations, which were often not of concern in
      HIES patients, have been shown to be highly related to HIES. For example, a
      significantly high frequency of vascular and gastrointestinal abnormities has
      been reported in STAT3-deficient AD-HIES patients. These new findings might help
      to provide new clues to the functional study of these HIES-related genes. This
      review summarizes and compares the major clinical manifestations of different
      subtypes of HIES, and we suggest that the incidence and severity of otitis media
      should not be underestimated in HIES patients.

PMID- 30112674
TI  - Tannic acid-modified silver nanoparticles as a novel therapeutic agent against
      Acanthamoeba.
AB  - Free-living amoebae belonging to Acanthamoeba genus are widely distributed
      protozoans which are able to cause infection in humans and other animals such as
      keratitis and encephalitis. Acanthamoeba keratitis is a vision-threatening
      corneal infection with currently no available fully effective treatment.
      Moreover, the available therapeutic options are insufficient and are very toxic
      to the eye. Therefore, there is an urgent need for the development of more
      effective anti-amoebic agents. Nanotechnology approaches have been recently
      reported to be useful for the elucidation antimicrobial, antiviral, antifungal
      and antiprotozoal activities and thus, they could be a good approach for the
      development of anti-Acanthamoeba agents. Therefore, this study was aimed to
      explore the activity and cytotoxicity of tannic acid-modified silver
      nanoparticles, pure silver nanoparticles and pure gold nanoparticles against
      clinical strains of Acanthamoeba spp. The obtained results showed a significant
      anti-amoebic effect of the tannic acid-modified silver nanoparticles which also
      presented low cytotoxicity. Moreover, tannic acid-modified silver nanoparticles
      were well absorbed by the trophozoites and did not induce encystation. On the
      other hand, pure silver nanoparticles were only slightly active against the
      trophozoite stage and pure gold nanoparticles did not show any activity. In
      conclusion and based on the observed results, silver nanoparticle conjugation
      with tannic acid may be considered as potential agent against Acanthamoeba spp.

PMID- 30112675
TI  - Artificial intelligence as a medical device in radiology: ethical and regulatory
      issues in Europe and the United States.
AB  - Worldwide interest in artificial intelligence (AI) applications is growing
      rapidly. In medicine, devices based on machine/deep learning have proliferated,
      especially for image analysis, presaging new significant challenges for the
      utility of AI in healthcare. This inevitably raises numerous legal and ethical
      questions. In this paper we analyse the state of AI regulation in the context of
      medical device development, and strategies to make AI applications safe and
      useful in the future. We analyse the legal framework regulating medical devices
      and data protection in Europe and in the United States, assessing developments
      that are currently taking place. The European Union (EU) is reforming these
      fields with new legislation (General Data Protection Regulation [GDPR],
      Cybersecurity Directive, Medical Devices Regulation, In Vitro Diagnostic Medical
      Device Regulation). This reform is gradual, but it has now made its first impact,
      with the GDPR and the Cybersecurity Directive having taken effect in May, 2018.
      As regards the United States (U.S.), the regulatory scene is predominantly
      controlled by the Food and Drug Administration. This paper considers issues of
      accountability, both legal and ethical. The processes of medical device decision
      making are largely unpredictable, therefore holding the creators accountable for
      it clearly raises concerns. There is a lot that can be done in order to regulate
      AI applications. If this is done properly and timely, the potentiality of AI
      based technology, in radiology as well as in other fields, will be invaluable.
      TEACHING POINTS: * AI applications are medical devices supporting
      detection/diagnosis, work-flow, cost-effectiveness. * Regulations for safety,
      privacy protection, and ethical use of sensitive information are needed. * EU and
      U.S. have different approaches for approving and regulating new medical devices.
      * EU laws consider cyberattacks, incidents (notification and minimisation), and
      service continuity. * U.S. laws ask for opt-in data processing and use as well as
      for clear consumer consent.

PMID- 30112676
TI  - Radiological findings of complications after lung transplantation.
AB  - Complications following lung transplantation may impede allograft function and
      threaten patient survival. The five main complications after lung transplantation
      are primary graft dysfunction, post-surgical complications, alloimmune responses,
      infections, and malignancy. Primary graft dysfunction, a transient
      ischemic/reperfusion injury, appears as a pulmonary edema in almost every patient
      during the first three days post-surgery. Post-surgical dysfunction could be
      depicted on computed tomography (CT), such as bronchial anastomosis dehiscence,
      bronchial stenosis and bronchomalacia, pulmonary artery stenosis, and size
      mismatch. Alloimmune responses represent acute rejection or chronic lung
      allograft dysfunction (CLAD). CLAD has three different forms (bronchiolitis
      obliterans syndrome, restrictive allograft syndrome, acute fibrinoid organizing
      pneumonia) that could be differentiated on CT. Infections are different depending
      on their time of occurrence. The first post-operative month is mostly associated
      with bacterial and fungal pathogens. From the second to sixth months, viral
      pneumonias and fungal and parasitic opportunistic infections are more frequent.
      Different patterns according to the type of infection exist on CT. Malignancy
      should be depicted and corresponded principally to post-transplantation
      lymphoproliferative disease (PTLD). In this review, we describe specific CT signs
      of these five main lung transplantation complications and their time of
      occurrence to improve diagnosis, follow-up, medical management, and to correlate
      these findings with pathology results. KEY POINTS: * The five main complications
      are primary graft dysfunction, surgical, alloimmune, infectious, and malignancy
      complications. * CT identifies anomalies in the setting of unspecific symptoms of
      lung transplantation complications. * Knowledge of the specific CT signs can
      allow a prompt diagnosis. * CT signs maximize the yield of bronchoscopy,
      transbronchial biopsy, and bronchoalveolar lavage. * Radiopathological
      correlation helps to understand CT signs after lung transplantation
      complications.

PMID- 30112677
TI  - The influence of the configuration of the (C70)2 dimer on its rovibrational
      spectroscopic properties: a theoretical survey.
AB  - A study of the spectroscopic properties of the buckyball dimer (C70)2 was
      performed, which involved mapping the potential energy curve of this system. The
      spectroscopic constants of the system were obtained using theoretical Dunham and
      discrete variable representation methods, as well as the Rydberg analytical
      function expanded to the sixth degree. Because the fullerenes in the dimer have
      both hexagonal and pentagonal faces, the properties of (C70)2 were examined for
      different system configurations. The fullerene dimerization process involves a
      weak interaction, possibly mediated by short-range components such as van der
      Waals forces. The differences between the spectroscopic constants of the various
      (C70)2 configurations and between their dissociation energies De were found to be
      rather small, which can be attributed to the dominant influence of the hexagonal
      faces of the fullerenes on the interaction between the fullerenes. These results
      should aid our understanding of the process of fullerene dimer formation and
      hopefully facilitate the development and application of new materials based on
      these dimers. Graphical Abstract Comparison of the potential energy curve and a
      schematic representation for the all (C70)2 fullerenes dimers configurations.

PMID- 30112678
TI  - Magnetic compression anastomosis for the complete dehiscence of
      hepaticojejunostomy in a patient after living-donor liver transplantation.
AB  - BACKGROUND: Magnetic compression anastomosis (MCA) is a minimally invasive method
      of anastomosis that does not involve a surgical procedure in patients with
      stricture, obstruction, or dehiscence of anastomosis after surgery. We
      experienced a case of complete dehiscence of bilioenteric anastomosis that was
      successfully treated by MCA. CASE PRESENTATION: A 55-year-old woman received ABO
      incompatible right-lobe living-donor liver transplantation with
      hepaticojejunostomy for the right anterior duct (RAD) and right posterior duct
      (RPD). Nineteen days after the operation, bilious and bloody discharge was
      detected from the abdominal drain. We performed an emergency operation and found
      that the anastomosis was completely dehiscent. We placed bile drainage catheters
      into the stumps of the RAD and RPD. She repeatedly experienced cholangitis after
      the surgery, so we added percutaneous transhepatic cholangial drainage (PTCD)
      tubes. We decided to treat the complete dehiscence of anastomosis by MCA. One
      year after the liver transplantation, we performed MCA for the RAD. The
      bilioenteric fistula was completed 21 days after MCA, and the magnets were
      retrieved by double-balloon endoscopy. Two months later, MCA for the RPD was also
      performed by the same procedure. The bilioenteric fistula was not completely
      established, so we performed double-balloon endoscopy and pulled the magnets down
      47 days after MCA for the RAD. The internal/external bile drainage tubes were
      then left in place to maintain the bilioenteric fistula. Twelve months after MCA
      for the RAD and 19 months after MCA for the RPD, we removed the tubes without any
      complications. CONCLUSION: Magnetic compression anastomosis for stricture,
      obstruction, or dehiscence of the anastomosis after living-donor liver
      transplantation was an effective and safe procedure.

PMID- 30112671
TI  - The brain-adipocyte-gut network: Linking obesity and depression subtypes.
AB  - Major depressive disorder (MDD) and obesity are dominant and inter-related health
      burdens. Obesity is a risk factor for MDD, and there is evidence MDD increases
      risk of obesity. However, description of a bidirectional relationship between
      obesity and MDD is misleading, as closer examination reveals distinct
      unidirectional relationships in MDD subtypes. MDD is frequently associated with
      weight loss, although obesity promotes MDD. In contrast, MDD with atypical
      features (MDD-AF) is characterised by subsequent weight gain and obesity. The
      bases of these distinct associations remain to be detailed, with conflicting
      findings clouding interpretation. These associations can be viewed within a
      systems biology framework-the psycho-immune neuroendocrine (PINE) network shared
      between MDD and metabolic disorders. Shared PINE subsystem perturbations may
      underlie increased MDD in overweight and obese people (obesity-associated
      depression), while obesity in MDD-AF (depression-associated obesity) involves
      more complex interactions between behavioural and biomolecular changes. In the
      former, the chronic PINE dysfunction triggering MDD is augmented by obesity
      dependent dysregulation in shared networks, including inflammatory, leptin
      ghrelin, neuroendocrine, and gut microbiome systems, influenced by chronic image
      associated psychological stress (particularly in younger or female patients). In
      MDD-AF, behavioural dysregulation, including hypersensitivity to interpersonal
      rejection, fundamentally underpins energy imbalance (involving hyperphagia,
      lethargy, hypersomnia), with evolving obesity exaggerating these drivers via
      positive feedback (and potentially augmenting PINE disruption). In both settings,
      sex and age are important determinants of outcome, associated with differences in
      emotional versus cognitive dysregulation. A systems biology approach is
      recommended for further research into the pathophysiological networks underlying
      MDD and linking depression and obesity.

PMID- 30112679
TI  - Inpatient Glycemic Management of the Pregnant Patient.
AB  - PURPOSE OF REVIEW: There is a rising prevalence of type 1 diabetes (T1DM), type 2
      diabetes (T2DM), and gestational diabetes (GDM) in pregnancy. Reaching and
      maintaining glycemic targets during and after this time are important for both
      the health of the mother and her baby. RECENT FINDINGS: Based on recently
      published guidelines from various societies, we review the diagnosis of diabetes
      in pregnancy, types of therapies available to maintain euglycemia, important keys
      to management of T1DM, T2DM, and GDM, and strategies for reaching inpatient
      glycemic targets during the peripartum period. Care for pregnant patients with
      T1DM is especially challenging, and providers should be aware of the varying
      insulin requirements at different stages of pregnancy and how to reduce
      hypoglycemia and avoid diabetic ketoacidosis. Insulin sensitivity fluctuates
      throughout pregnancy due to physiologic changes, especially during labor and
      delivery and immediately post-partum. We review recommendations regarding how to
      manage this dynamic time and present our own institution's inpatient management
      protocol. Finally, we review management of diabetes post-partum, including
      medications, breast-feeding, and continued monitoring and screening. With the
      collaborative efforts of the patient and an interdisciplinary team and in-depth
      knowledge of the most up-to-date management principles, it is possible to achieve
      euglycemia during this critical time of a mother and baby's life.

PMID- 30112680
TI  - Post-operative pain control following arthroscopic rotator cuff repair: peri
      articular injection versus interscalene brachial plexus block.
AB  - PURPOSE: To compare post-operative pain relief with peri-articular injection (PI)
      versus interscalene brachial plexus block (IBPB) after arthroscopic rotator cuff
      repair (ARCR) surgery. METHODS: We retrospectively reviewed 121 consecutive
      patients undergoing ARCR surgery divided into two groups: the PI group and the
      IBPB group. We compared complications and self-reported pain score measured using
      a Numerical Rating Scale (NRS) during the initial 24 hours after surgery.
      RESULTS: The NRS scores recorded in the recovery room (0), 0.5, and four hours
      post-operatively were higher in the PI group (n = 38) than the IBPB group (n =
      52) (2.1 vs. 0.8, p = 0.014; 1.4 vs. 0.5, p = 0.0069; and 1.3 vs. 0.5, p = 0.012,
      respectively). However, the NRS scores recorded at 16, 20, and 24 hours post
      operatively were lower in the PI group than in the IBPB group (1.4 vs. 3.1, p <
      0.0001; 1.4 vs. 3.2, p < 0.0001; and 1.7 vs. 3.2, p = 0.00046, respectively). The
      incidences of post-operative nausea and temporary numbness in the upper arm were
      significantly lower in the PI group than in the IBPB group (7.9% vs. 33%, p =
      0.0052; and 13% vs. 85%, p < 0.0001, respectively). CONCLUSIONS: Although IBPB
      provided superior pain control during the initial few hours after ARCR surgery,
      PI was superior from 16 to 24 hours post-operatively. The rates of side effects,
      such as nausea and temporary arm numbness, were also lower in the PI group than
      in the IBPB group.

PMID- 30112681
TI  - Procedure for single-stage implant retention for chronic periprosthetic infection
      using topical degradable calcium-based antibiotics.
AB  - INTRODUCTION: Surgical treatment using DAIR (debridement, systemic antibiotics,
      and implant retention) can lead to high rates of treatment success in cases of
      early periprosthetic joint infection (PJI) but can fail in late-onset cases.
      Supplementary local antibiotic therapy is not yet generally established and lacks
      evidence-based proof of efficacy. The aim of this study was to analyze DAIR
      outcomes in recurrent PJI cases and patients who are not suitable for a two-stage
      exchange, using additional degradable calcium-based antibiotics. METHODS: All
      patients fulfilled the Infectious Diseases Society of America (IDSA) guidelines
      for chronic late-onset PJI but were not suitable for a multistage procedure
      because of their individual operation risk. A total of 42 patients (mean age, 73
      years) were treated using a single-stage algorithm consisting of DAIR, followed
      by implantation of degradable antibiotics chosen in accordance with an
      antibiogram. OSTEOSET(r) (admixed ceftriaxone/vancomycin/tobramycin) and Herafill
      Gentamycin(r) were used as carrier systems. The follow-up period was 23 months
      (+/- SD, 10.3). The study is based on institutional review board (IRB) approval.
      RESULTS: The clinical entities were chronic PJI of the hip (45.2%), knee (28.6%),
      and knee arthrodesis (26.2%). The bacterial spectrum was composed of
      Staphylococcus epidermidis (29%), Staphylococcus aureus (21%), and Enterococcus
      faecalis (21%). 21.4% showed a combination of two or more bacteria. In 73.8%,
      permanent remission was achieved, while 11.9% showed chronic PJI under implant
      retention. Implant retention could be achieved in 85.7%. CONCLUSION: DAIR usually
      shows low levels of success in difficult-to-treat cases. However, we could
      demonstrate the successful treatment of patients with recurrent PJI (typically
      considered DAIR-inappropriate) using degradable antibiogram-based topical calcium
      based antibiotics. Over 70% of the cases went to remission and over 85% of the
      implants could be retained.

PMID- 30112682
TI  - Intra-operative cell salvage in pelvic and acetabular fracture surgery: a
      retrospective comparative study.
AB  - AIM OF THE STUDY: To determine if the intraoperative use of cell salvage (CS) led
      to a decrease in allogeneic blood transfusion by comparing with a control group
      that did not receive CS. We also looked at the effects of injury severity and
      surgical approach. METHODS: This was a retrospective study at a major trauma
      center. One hundred and nineteen patients underwent open reduction and internal
      fixation of pelvic and acetabular fractures with (59 patients) or without intra
      operative blood cell salvage (60 patients). The main outcome measurements were
      allogeneic blood transfusion during and after surgery with respect to CS, injury
      severity and surgical approach. RESULTS: We did not find any significant
      difference in the allogeneic blood transfusion between the CS and non-CS groups
      (rate-62% vs. 48%, p value 0.12 {significant at < 0.05}, volume 5.56 units vs.
      5.58 units, p value 0.33). The rate (71.1% vs. 48.9%, p = 0.02) and volume (7.6
      units vs. 4.3 units, p value 0.00057) of post-operative blood transfusion was
      significantly higher in the more severely injured (ISS > 20), but there was no
      significant difference between the CS and non-CS groups. No significant
      difference was seen between either patients who had anterior or posterior
      surgical approaches. CONCLUSIONS: We did not find CS clearly efficacious
      clinically or cost effective, even in the more severely injured patients or when
      different surgical approaches were used. We do not advocate the routine use of CS
      in pelvic and acetabular surgery, but selectively, based on surgeon and patient
      preference.

PMID- 30112685
TI  - Truly Reconciling the Case of Jahi McMath.
AB  - This article clarifies some issues raised by Dr. Ariane Lewis in her recent
      "Current Opinion/Arguments" article on the case of Jahi McMath. Review of case
      materials. Jahi's case most likely represents an instance of global ischemic
      penumbra (GIP) mimicking brain death (BD), with intracranial blood flow too low
      to support neuronal function or to be detected by radionuclide scan but
      sufficient to prevent widespread necrosis. Her MRI scan 9 months after the
      ischemic insult showed gross preservation of cortical and internal structures,
      incompatible with there ever having been a period of completely absent blood
      flow. Regarding Jahi's alleged intermittent responsiveness, the set of videos,
      unsystematic as they are, constitutes convincing evidence that her movements in
      seeming response to command are not of spinal cord origin and are indeed
      voluntary responses, placing her in the category of minimally conscious state
      (MCS). In the absence of serial examinations by experts in MCS, the benefit of
      the doubt should be given. Unfortunately, her death on June 22, 2018, 41/2 years
      after the diagnosis of BD, precludes such examinations. During those 41/2 years,
      Jahi underwent menarche, with three documented menstrual periods, and ongoing
      pubertal development. Her case is an important example of false-positive
      diagnosis of BD, demonstrating the inability of current diagnostic standards to
      distinguish true BD from potentially reversible brain nonfunction due to GIP. The
      incidence of such mimicry is impossible to determine, because in most cases a BD
      diagnosis becomes a self-fulfilling prophecy.

PMID- 30112684
TI  - Development, growth, and biomass simulations of two common wetland tree species
      in Texas.
AB  - Monitoring the health and condition of wetlands using biological assessments can
      serve as an effective tool for environmental managers to better evaluate and
      monitor the status and trends of their wetland ecosystems. Woody species can be
      used as conspicuous biological assessment tools due to their direct response to
      environmental change, such as hydrologic alteration. The purpose of this study is
      to use field-measured morphological measurement indices to develop and optimize
      tree growth parameters and growth curves using multi-model combination approach
      to improve tree biomass estimations. Field morphological investigations were
      conducted for two common wetland tree species in Texas. A range of morphological
      characteristics including leaf area index, height, and biomass was measured for
      black willow (Salix nigra Marsh) and green ash (Fraxinus pennsylvanica) sampled
      from 15 sites in a wetland near Cameron, Texas. The measured morphological
      parameters were used to optimize tree growth and development with the ALMANAC
      model. The developed tree growth parameters and growth curves were subsequently
      used in the APEX model to simulate tree biomass at the catchment scale. Both
      models accurately simulated biomass of trees growing in the wetland. This
      accurate biomass prediction will be useful to advance science to better monitor
      and assess wetland health on a large scale (e.g. national or global).

PMID- 30112686
TI  - The Prognostic Value of Simplified EEG in Out-of-Hospital Cardiac Arrest
      Patients.
AB  - BACKGROUND: We previously validated simplified electroencephalogram (EEG)
      tracings obtained by a bispectral index (BIS) device against standard EEG. This
      retrospective study now investigated whether BIS EEG tracings can predict
      neurological outcome after cardiac arrest (CA). METHODS: Bilateral BIS monitoring
      (BIS VISTATM, Aspect Medical Systems, Inc. Norwood, USA) was started following
      intensive care unit admission. Six, 12, 18, 24, 36 and 48 h after targeted
      temperature management (TTM) at 33  degrees C was started, BIS EEG tracings were
      extracted and reviewed by two neurophysiologists for the presence of slow diffuse
      rhythm, burst suppression, cerebral inactivity and epileptic activity (defined as
      continuous, monomorphic, > 2 Hz generalized sharp activity or continuous,
      monomorphic, < 2 Hz generalized blunt activity). At 180 days post-CA,
      neurological outcome was determined using cerebral performance category (CPC)
      classification (CPC1-2: good and CPC3-5: poor neurological outcome). RESULTS:
      Sixty-three out-of-hospital cardiac arrest patients were enrolled for data
      analysis of whom 32 had a good and 31 a poor neurological outcome. Epileptic
      activity within 6-12 h predicted CPC3-5 with a positive predictive value (PPV) of
      100%. Epileptic activity within time frames 18-24 and 36-48 h showed a PPV for
      CPC3-5 of 90 and 93%, respectively. Cerebral inactivity within 6-12 h predicted
      CPC3-5 with a PPV of 57%. In contrast, cerebral inactivity between 36 and 48 h
      predicted CPC3-5 with a PPV of 100%. The pattern with the worst predictive power
      at any time point was burst suppression with PPV of 44, 57 and 40% at 6-12 h, at
      18-24 h and at 36-48 h, respectively. Slow diffuse rhythms at 6-12 h, at 18-24 h
      and at 36-48 h predicted CPC1-2 with PPV of 74, 76 and 80%, respectively.
      CONCLUSION: Based on simplified BIS EEG, the presence of epileptic activity at
      any time and cerebral inactivity after the end of TTM may assist poor outcome
      prognostication in successfully resuscitated CA patients. A slow diffuse rhythm
      at any time after CA was indicative for a good neurological outcome.

PMID- 30112687
TI  - Biomarkers of islet beta cell stress and death in type 1 diabetes.
AB  - Recent work on the pathogenesis of type 1 diabetes has led to an evolving
      recognition of the heterogeneity of this disease, both with regards to clinical
      phenotype and responses to therapies to prevent or revert diabetes. This
      heterogeneity not only limits efforts to accurately predict clinical disease but
      also is reflected in differing responses to immunomodulatory therapeutics. Thus,
      there is a need for robust biomarkers of beta cell health, which could provide
      insight into pathophysiological differences in disease course, improve disease
      prediction, increase the understanding of therapeutic responses to
      immunomodulatory interventions and identify individuals most likely to benefit
      from these therapies. In this review, we outline current literature, limitations
      and future directions for promising circulating markers of beta cell stress and
      death in type 1 diabetes, including markers indicating abnormal prohormone
      processing, circulating RNAs and circulating DNAs.

PMID- 30112688
TI  - Muller glial dysfunction during diabetic retinopathy in rats is reduced by the
      acrolein-scavenging drug, 2-hydrazino-4,6-dimethylpyrimidine.
AB  - AIMS/HYPOTHESIS: Recent studies suggest that abnormal function in Muller glial
      cells plays an important role in the pathogenesis of diabetic retinopathy. This
      is associated with the selective accumulation of the acrolein-derived advanced
      lipoxidation end-product, Nepsilon-(3-formyl-3,4-dehydropiperidino)lysine (FDP
      lysine), on Muller cell proteins. The aim of the current study was to identify
      more efficacious acrolein-scavenging drugs and determine the effects of the most
      potent on Muller cell FDP-lysine accumulation and neuroretinal dysfunction during
      diabetes. METHODS: An ELISA-based in vitro assay was optimised to compare the
      acrolein-scavenging abilities of a range of drugs. This identified 2-hydrazino
      4,6-dimethylpyrimidine (2-HDP) as a new and potent acrolein scavenger. The
      ability of this agent to modify the development of diabetic retinopathy was
      tested in vivo. Male Sprague Dawley rats were divided into three groups: (1) non
      diabetic; (2) streptozotocin-induced diabetic; and (3) diabetic treated with 2
      HDP in their drinking water for the duration of diabetes. Liquid chromatography
      high-resolution mass spectrometry was used to detect 2-HDP reaction products in
      the retina. Immunohistochemistry, real-time quantitative (q)RT-PCR and
      electroretinography were used to assess retinal changes 3 months after diabetes
      induction. RESULTS: 2-HDP was the most potent of six acrolein-scavenging agents
      tested in vitro (p < 0.05). In vivo, administration of 2-HDP reduced Muller cell
      accumulation of FDP-lysine at 3 months in rats rendered diabetic with
      streptozotocin (p < 0.001). A 2-HDP adduct was identified in the retinas of
      diabetic animals treated with this compound. 2-HDP supplementation was associated
      with reduced Muller cell gliosis (p < 0.05), reduced expression of the oxidative
      stress marker haem oxygenase-1 (p < 0.001) and partial normalisation of inwardly
      rectifying K+ channel 4.1 (Kir4.1) expression (p < 0.001 for staining in
      perivascular regions and the innermost region of the ganglion cell layer).
      Diabetes-induced retinal expression of inflammatory markers, inflammatory
      signalling compounds and activation of retinal microglial cells were all reduced
      in 2-HDP-treated animals. Retinal neurophysiological defects in diabetic animals,
      as indicated by changes in the electroretinogram 7 weeks after induction of
      diabetes, were also reduced by 2-HDP (p < 0.05-0.01 for b-wave amplitudes at
      flash intensities from -10 to +10 dB; p < 0.01 for time to peak of summed
      oscillatory potentials at +10 dB). CONCLUSIONS/INTERPRETATION: These findings
      support the hypothesis that Muller cell accumulation of FDP-lysine plays an
      important role in the development of diabetic retinopathy. Our results also
      suggest that 2-HDP may have therapeutic potential for delaying or treating this
      sight-threatening complication.

PMID- 30112689
TI  - Impact of daily incremental change in environmental temperature on beta cell
      function and the risk of gestational diabetes in pregnant women.
AB  - AIMS/HYPOTHESIS: The prevalence of gestational diabetes (GDM) is higher in summer
      months, possibly reflecting an association between ambient temperature and blood
      glucose levels. However, the specific exposure and mechanism by which temperature
      may affect glucose metabolism in pregnancy remains unclear. We systematically
      evaluated the relationships of environmental temperature and changes therein over
      varying durations of exposure time with beta cell function, insulin sensitivity
      and glucose tolerance in women undergoing antepartum screening for GDM. METHODS:
      At a mean gestation of 29 weeks, 1464 women in Toronto (ON, Canada) underwent an
      OGTT, from which 318 were diagnosed with GDM. Blood glucose, beta cell function
      and insulin sensitivity were evaluated in relation to 18 temperature variables:
      mean temperature and change in temperature on the day of the OGTT and over the
      preceding 7, 14, 21, 28, 35, 42, 49 and 56 days, respectively. RESULTS:
      Temperature changes in the preceding 14, 21, 28, 35, 42, 49 and 56 days (rather
      than mean temperatures) emerged as independent predictors of blood glucose. These
      relationships were evident in months where mean daily temperature was rising
      (February - July), but not in those where it was falling (August - January).
      Indeed, in February - July, the temperature changes in the preceding 21, 28 and
      35 days emerged as predictors of both poorer beta cell function and higher blood
      glucose. Moreover, in February - July, the changes in temperature in the
      preceding 21 days (OR 1.16, 95% CI 1.01, 1.33) and 28 days (OR 1.20, 95% CI 1.03,
      1.39) were independent predictors of GDM, while mean temperatures were not.
      CONCLUSIONS/INTERPRETATION: In pregnant women, rising environmental temperature
      in the 3-4 weeks prior to glucose tolerance testing may be associated with beta
      cell dysfunction and an increased risk of GDM.

PMID- 30112690
TI  - Prognostic impact of the ankle-brachial index on the development of micro- and
      macrovascular complications in individuals with type 2 diabetes: the Rio de
      Janeiro Type 2 Diabetes Cohort Study.
AB  - AIMS/HYPOTHESIS: The prognostic importance of the ankle-brachial index (ABI) in
      individuals with diabetes is controversial. We aimed to evaluate the relationship
      between the ABI and the occurrence of micro- and macrovascular complications in
      individuals with type 2 diabetes. METHODS: The ABI was measured at baseline in
      668 individuals with type 2 diabetes, and the individuals were followed-up for a
      median of 10 years. Multivariate Cox analysis was used to examine associations
      between the ABI and the occurrence of microvascular (retinopathy,
      microalbuminuria, renal function deterioration and peripheral neuropathy) and
      macrovascular (total cardiovascular events, major adverse cardiovascular events
      [MACE] and cardiovascular mortality) complications, and all-cause mortality. The
      improvement in risk stratification was assessed using the C statistic and the
      integrated discrimination improvement (IDI) index. RESULTS: During follow-up, 168
      individuals had a cardiovascular event (140 MACE) and 191 individuals died (92
      cardiovascular deaths); 156 individuals newly developed or experienced worsening
      diabetic retinopathy, 194 achieved the renal composite outcome (122 with newly
      developed microalbuminuria and 93 with deteriorating renal function) and 95 newly
      developed or experienced worsening peripheral neuropathy. The ABI, either
      analysed as a continuous or as a categorical variable, was significantly
      associated with all macrovascular and mortality outcomes, except for non
      cardiovascular mortality. Individuals with a baseline ABI of <=0.90 had a 2.1
      fold increased risk of all-cause mortality (95% CI 1.3, 3.5; p = 0.004), a 2.7
      fold excess risk of cardiovascular mortality (95% CI 1.4, 5.4; p = 0.004) and a
      2.5-fold increased risk of MACE (95% CI 1.5, 4.4; p = 0.001). The ABI improved
      risk discrimination over classical risk factors, with relative IDIs ranging from
      6.3% (for all-cause mortality) to 31% (for cardiovascular mortality). In
      addition, an ABI of <=0.90 was associated with the development or worsening of
      peripheral neuropathy (2.1-fold increased risk [95% CI 1.1, 4.3]; p = 0.033), but
      not with retinopathy or renal outcomes. CONCLUSIONS/INTERPRETATION: A low ABI is
      associated with excess risk of adverse cardiovascular outcomes, mortality and
      peripheral neuropathy development or worsening, and improves cardiovascular risk
      stratification. The ABI should therefore be routinely evaluated in individuals
      with type 2 diabetes.

PMID- 30112691
TI  - Prognostic Factors of Extramammary Paget's Disease.
AB  - OPINION STATEMENT: Most patients with extramammary Paget's disease (EMPD) show a
      good prognosis; however, some patients develop fatal metastases. Early detection
      is important for improving prognosis, due to the difficulties associated with the
      treatment of distant EMPD metastases. Several studies have emphasized the
      importance of the invasion level of the primary lesion for predicting the
      presence of metastasis, and deeper invasion or increased thickness is correlated
      with poorer prognosis. Vascular tumor invasion of the primary lesion can also
      predict the risk of metastasis. Lymph node metastasis is a strong indicator for
      poor prognosis, and the number of lymph node metastases affects patient outcome,
      in that there is a significant difference in survival between patients with zero
      or one lymph node metastasis and those with more than two lymph node metastases.
      Serum markers may be able to predict the presence of systemic metastases, and
      carcinoembryonic antigen and cytokeratin 19 fragment 21-1 reflect disease
      progression and may be clinically valuable. Although several genetic alterations
      have been determined for EMPD, factors determining prognosis should be further
      explored.

PMID- 30112693
TI  - Dexmedetomidine Protects Against Chemical Hypoxia-Induced Neurotoxicity in
      Differentiated PC12 Cells Via Inhibition of NADPH Oxidase 2-Mediated Oxidative
      Stress.
AB  - Dexmedetomidine (Dex) is a widely used sedative in anesthesia and critical care
      units, and it exhibits neuroprotective activity. However, the precise mechanism
      of Dex-exerted neuroprotection is not clear. Increased neuronal NADPH oxidase 2
      (NOX2) contributes to oxidative stress and neuronal damage in various hypoxia
      related neurodegenerative disorders. The present study investigated whether Dex
      regulated neuronal NOX2 to exert its protective effects under hypoxic conditions.
      Well-differentiated PC12 cells were exposed to cobalt chloride (CoCl2) to mimic a
      neuronal model of chemical hypoxia-mediated neurotoxicity. The data showed that
      Dex pretreatment of PC12 cells significantly suppressed CoCl2-induced
      neurotoxicity, as evidenced by the enhanced cell viability, restoration of
      cellular morphology, and reduction in apoptotic cells. Dex improved mitochondrial
      function and inhibited CoCl2-induced mitochondrial apoptotic pathways. We further
      demonstrated that Dex attenuated oxidative stress, downregulated NOX2 protein
      expression and activity, and inhibited intracellular calcium ([Ca2+]i) overload
      in CoCl2-treated PC12 cells. Moreover, knockdown of the NOX2 gene markedly
      improved mitochondrial function and attenuated apoptosis under hypoxic
      conditions. These results demonstrated that the protective effects of Dex against
      hypoxia-induced neurotoxicity in neural cells were mediated, at least partially,
      via inhibition of NOX2-mediated oxidative stress.

PMID- 30112692
TI  - Evolution of adjuvant treatment in endometrial cancer-no evidence and new
      questions?
AB  - PURPOSE: For endometrial cancer (EC), clinical and pathological risk factors are
      taken to triage patients and estimate their prognosis. Lymph node involvement
      (pN+), lymphovascular space involvement (LSVI), grading, age of the patients, and
      T classification are internationally accepted parameters for treatment decisions.
      MATERIALS AND METHODS: Studies on adjuvant radiation, chemotherapy, and
      chemoradiation are discussed against the background of risk stratification and
      clinical decision-making in early-to-advanced stage endometrial cancer. Recent
      publications on adjuvant treatment in high-risk disease and its implications for
      the patients with regard to expected oncologic benefit and treatment-related
      toxicity are discussed. RESULTS: Surgery is the mainstay of treatment of EC
      patients. Well-differentiated tumors and early disease (FIGO IA) should be
      followed up without further treatment. In FIGO I stage without risk factors, VBT
      remains the standard treatment after surgery. FIGO I, II patients with one or
      more risk factors (MI >= 50%, Grading[G]3, age >60 years, LVSI) benefit from
      external beam radiotherapy (EBRT) in terms of survival. There are no data of
      acceptable quality demonstrating that chemotherapy is superior to radiation in
      locally advanced carcinomas. Therefore, even in locally advanced disease (FIGO
      III, IV), EBRT remains the standard of care after surgery. EBRT contributes to
      the very low rate of local relapses and better DFS in these patients and should
      not be replaced by chemotherapy only. Whether and which subgroups of patients
      benefit from an additional (concomitant and/or adjuvant) chemotherapy in terms of
      disease-free survival remains a controversial issue. The recently published
      PORTEC-3 trial could not create clear evidence. With a high rate of isolated
      tumors cells and micrometastases in the specimens, the increasing use of
      unvalidated sentinel concepts in endometrial cancer raises more questions with
      regard to indications for adjuvant treatment. In the future, integrated genomic
      characterization of tumors might be helpful for treatment individualization in
      the adjuvant setting.

PMID- 30112694
TI  - Current-Induced Domain Wall Motion and Tilting in Perpendicularly Magnetized
      Racetracks.
AB  - The influence of C insertion on Dzyaloshinskii-Moriya interaction (DMI) as well
      as current-induced domain wall (DW) motion (CIDWM) and tilting in Pt/Co/Ta
      racetracks is investigated via a magneto-optical Kerr microscope. The similar DMI
      strength for Pt/Co/Ta and Pt/Co/C/Ta samples reveals that DMI mainly comes from
      the Pt/Co interface. Fast DW velocity around tens of m/s with current density
      around several MA/cm2 is observed in Pt/Co/Ta. However, it needs double times
      larger current density to reach the same magnitude in Pt/Co/C/Ta, indicating DW
      velocity is related to the spin-orbit torque efficiency and pinning potential
      barrier. Moreover, in CIDWM, DW velocity is around 103 times larger than that in
      field-induced DW motion (FIDWM) with current-generated effective field keeping
      the same magnitude as applied magnetic field, revealing that the current
      generated Joule heating has an influence on DW motion. Interestingly, current
      induced DW tilting phenomenon is observed, while this phenomenon is absent in
      FIDWM, demonstrating that the current-generated Oersted field may also play an
      essential role in DW tilting. These findings could provide some designing
      prospects to drive DW motion in SOT-based racetrack memories.

PMID- 30112695
TI  - Immediate and later impacts of antimicrobial consumption on carbapenem-resistant
      Acinetobacter spp., Pseudomonas aeruginosa, and Klebsiella spp. in a teaching
      hospital in Brazil: a 10-year trend study.
AB  - To evaluate trends and the immediate and late impact of antimicrobial consumption
      on carbapenem-resistant Acinetobacter spp. (CRAs), carbapenem-resistant
      Pseudomonas aeruginosa (CRPA), and carbapenem-resistant Klebsiella spp. (CRKs)
      over a 10-year period. An ecological study was conducted at the teaching hospital
      in Sao Paulo, Brazil, from 2007 to 2016. Consumption and resistance data were
      collected from the supply sector and central laboratory of the institution,
      respectively. Associations between consumption and resistance were analyzed in
      the same year, 1 year later, and 2 years later by linear regression of mixed
      effects. A total of 22,041 isolates were analyzed. Among these, 9988 corresponded
      to the gram-negatives in this study [3682 (36.9%) were Klebsiella spp., 3169
      (31.7%) were P. aeruginosa, and 3137 (31.4%) were Acinetobacter spp.]. An
      increasing trend of consumption was observed, except for fourth-generation
      cephalosporins. Carbapenems were the most used antimicrobial class; CRKs
      presented a substantial increase over this period (from 1.4 to 67.0%; p = 0.001).
      Increased consumption of third-generation cephalosporins reduced CRAs [- 2.43%,
      95% confidence interval (CI), - 3.30 to - 1.57; p < 0.001] and increased CRPA
      [26.67%, 95% CI, 2.99 to 50.35; p = 0.034] in the same year. Increased
      consumption of beta-lactam/beta-lactamase inhibitors increased CRKs with a 1-year
      delay [5.13%, 95% CI, 2.40 to 7.86; p = 0.001]. Our study demonstrated high
      antimicrobial consumption and growing carbapenem-resistance rates among gram
      negative bacteria, especially Klebsiella spp., and the immediate and later
      effects of consumption of multiple antimicrobials on carbapenem resistance.

PMID- 30112696
TI  - A method for expansion of T cells from cynomolgus monkey (Macaca fascicularis).
AB  - T cells have been successfully applied to cancer immunotherapy. However, a
      challenge is an expansion of T cells from cynomolgus monkey, which is a valuable
      non-human primate model for T cell therapy transferring to the clinic. Here, we
      compared several strategies to expand cynomolgus monkey T cell and developed an
      appropriate method. Our study demonstrated that 100 ng/ml CD3 mAb + 1% PHA+ 1000
      U/ml IL2 therapy significantly expanded peripheral blood CD3+ T cells without
      compromising T cell phenotype in vitro. The results of this study could be used
      for T cell remodeling, which has significant therapeutic potential in Chimeric
      Antigen Receptor-T (CAR-T) cell immunotherapy.

PMID- 30112697
TI  - LncRNA-uc.40 silence promotes P19 embryonic cells differentiation to
      cardiomyocyte via the PBX1 gene.
AB  - Uc.40 is a long noncoding RNA that is highly conserved among different species,
      although its function is unknown. It is highly expressed in abnormal human
      embryonic heart. We previously reported that overexpression of uc.40 promoted
      apoptosis and inhibited proliferation of P19 cells, and downregulated PBX1, which
      was identified as a potential target gene of uc.40. The current study evaluated
      the effects of uc40-siRNA-44 (siRNA against uc.40) on the differentiation,
      proliferation, apoptosis, and mitochondrial function in P19 cells, and
      investigated the relationship between uc.40 and PBX1 in cardiomyocytes. The uc.40
      silencing expression was confirmed by quantitative real-time polymerase chain
      reaction (RT-PCR). Observation of morphological changes in transfected P19 cells
      during different stages of differentiation revealed that uc40-siRNA-44 increased
      the number of cardiomyocyes. There was no significant difference in the
      morphology or time of differentiation between the uc40-siRNA-44 group and the
      control group. uc40-siRNA-44 significantly promoted proliferation of P19 cells
      and inhibited serum starvation-induced apoptosis. There was no significant
      difference in mitochondrial DNA copy number or cellular ATP level between the two
      groups, and ROS levels were significantly decreased in uc40-siRNA-44-transfected
      cells. The levels of PBX1 and myocardial markers of differentiation were examined
      in transfected P19 cells; uc40-siRNA-44 downregulated myocardial markers and
      upregulated PBX1 expression. These results suggest that uc.40 may play an
      important role during the differentiation of P19 cells by regulation of PBX1 to
      promote proliferation and inhibit apoptosis. These studies provide a foundation
      for further study of uc.40/PBX1 in cardiac development.

PMID- 30112699
TI  - Marked Age-Related Changes in Brain Iron Homeostasis in Amyloid Protein Precursor
      Knockout Mice.
AB  - Proteolytic cleavage of the amyloid precursor protein (APP) into the Abeta
      peptide has been an extensively researched mechanism for Alzheimer's disease, but
      the normal function of the protein is less understood. APP functions to regulate
      neuronal iron content by stabilizing the surface presentation of ferroportin-the
      only iron exporter channel of cells. The present study aims to quantify the
      contribution of APP to brain and peripheral iron by examining the lifetime impact
      on brain and liver iron levels in APP knockout mice. Consistent with previous
      reports, we found that wild-type mice exhibited an age-dependent increase in iron
      and ferritin in the brain, while no age-dependent changes were observed in the
      liver. APP ablation resulted in an exaggeration of age-dependent iron
      accumulation in the brain and liver in mice that was assessed at 8, 12, 18, and
      22 months of age. Brain ferroportin levels were decreased in APP knockout mice,
      consistent with a mechanistic role for APP in stabilizing this iron export
      protein in the brain. Iron elevation in the brain and liver of APP knockout mice
      correlated with decreased transferrin receptor 1 and increased ferritin protein
      levels. However, no age-dependent increase in brain ferritin iron saturation was
      observed in APP-KO mice despite similar protein expression levels potentially
      explaining the vulnerability of APP-KO mice to parkinsonism and traumatic brain
      sequelae. Our results support a crucial role of APP in regulating brain and
      peripheral iron, and show that APP may act to oppose brain iron elevation during
      aging.

PMID- 30112698
TI  - Electrospinning of Carboxymethyl Chitosan/Polyoxyethylene Oxide Nanofibers for
      Fruit Fresh-Keeping.
AB  - Electrospinning provides an effective method for generating nanofibers from
      solution of carboxymethyl chitosan/polyoxyethylene oxide (CMCS/PEO). The goal of
      this work is to explore the potential application of electrospun CMCS/PEO
      nanofiber membrane in fruit fresh-keeping. The microstructure, antibacterial
      activity, hydrophilia, and air permeability of the nanofiber membrane have been
      tested. For comparison, the fresh-keeping effects of commercial cling wrap and
      CMCS/PEO nanofiber membranes on strawberries' rotting rate and weight loss rate
      have been studied. The results indicate that the electrospun CMCS/PEO membrane
      could effectively avoid water loss in strawberries and has a remarkable effect to
      prolong strawberries' shelf life due to its breathability and antibacterial
      activity. In addition, the composite CMCS/PEO, nanofiber membrane is non
      poisonous and edible, which can be used in food industry.

PMID- 30112700
TI  - Early Treatment with Quinidine in 2 Patients with Epilepsy of Infancy with
      Migrating Focal Seizures (EIMFS) Due to Gain-of-Function KCNT1 Mutations:
      Functional Studies, Clinical Responses, and Critical Issues for Personalized
      Therapy.
AB  - Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare early-onset
      developmental epileptic encephalopathy resistant to anti-epileptic drugs. The
      most common cause for EIMFS is a gain-of-function mutation in the KCNT1 potassium
      channel gene, and treatment with the KCNT1 blocker quinidine has been suggested
      as a rational approach for seizure control in EIMFS patients. However, variable
      results on the clinical efficacy of quinidine have been reported. In the present
      study, we provide a detailed description of the clinical, genetic, in vitro, and
      in vivo electrophysiological profile and pharmacological responses to quinidine
      of 2 EIMFS unrelated patients with a heterozygous de novo KCNT1 mutation:
      c.2849G>A (p.R950Q) in patient 1 and c.2677G>A (p.E893K) in patient 2. When
      expressed heterologously in CHO cells, KCNT1 channels carrying each variant
      showed gain-of-function effects, and were more effectively blocked by quinidine
      when compared to wild-type KCNT1 channels. On the basis of these in vitro
      results, add-on quinidine treatment was started at 3 and 16 months of age in
      patients 1 and 2, respectively. The results obtained reveal that quinidine
      significantly reduced seizure burden (by about 90%) and improved quality of life
      in both patients, but failed to normalize developmental milestones, which
      persisted as severely delayed. Based on the present experience, early quinidine
      intervention associated with heart monitoring and control of blood levels is
      among the critical factors for therapy effectiveness in EIMFS patients with KCNT1
      gain-of-function mutations. Multicenter studies are needed to establish a
      consensus protocol for patient recruitment, quinidine treatment modalities, and
      outcome evaluation, to optimize clinical efficacy and reduce risks as well as
      variability associated to quinidine use in such severe developmental
      encephalopathy.

PMID- 30112701
TI  - Inhibition of MyD88 Signaling Skews Microglia/Macrophage Polarization and
      Attenuates Neuronal Apoptosis in the Hippocampus After Status Epilepticus in
      Mice.
AB  - Inflammation is implicated in epileptogenesis. Activated microglia and
      macrophages (MG/MPhi) are found in the brains of patients with epilepsy-related
      diseases and animal models of epilepsy. It is not yet known how the MG/MPhi
      activation phenotype affects pathological changes in the brain after a single
      seizure. In this study, we had 2 main purposes: first, to characterize post
      status epilepticus (SE) inflammation by tracking MG/MPhi polarization, and,
      second, to explore the role of an innate immune receptor adaptor protein, namely,
      myeloid differentiation primary response gene 88 (MyD88), in the induction of SE
      in a mouse model. A lithium-pilocarpine model of seizure conditions was generated
      in C57BL/6 mice. The intensity and distribution of MG/MPhi polarization were
      tracked by fluorescent immunohistochemistry and Western blotting for the
      polarization markers inducible nitrogen oxygenized synthase, arginase-1, CD163,
      and mannose receptor. We observed steadily increasing M1 MG/MPhi along with MyD88
      signal upregulation after SE in the hippocampi of mice, whereas the M2 marker
      arginase-1 was localized mainly in astrocytes rather than in MG/MPhi. Inhibition
      or gene knockout of MyD88 reduced M1 MG/MPhi and gliosis although increasing M2
      MG/MPhi in the hippocampi of SE mice. MyD88 inhibition also augmented glutamate
      transporter 1 expression and reduced N-methyl-D-aspartate receptor NR1 subunit
      expression in the hippocampus to protect pyramidal neurons from apoptosis. These
      data suggest that MG/MPhi polarization after SE impacts the pathological outcome
      of the hippocampus via MyD88 signaling and point to MyD88 as a potential
      neuroprotective target for epilepsy therapy.

PMID- 30112702
TI  - Oncologic Impact of Lymph Node Dissection for Intrahepatic Cholangiocarcinoma: a
      Propensity Score-Matched Study.
AB  - BACKGROUND: Intrahepatic cholangiocarcinoma is a malignancy of the intrahepatic
      biliary tree. Although surgical resection is the mainstay of treatment for this
      tumor, the impact of lymph node dissection during hepatectomy is controversial.
      In this study, we evaluated the impact of lymph node dissection during surgical
      resection for intrahepatic cholangiocarcinoma. METHODS: Records from 170 patients
      who underwent radical hepatectomy for intrahepatic cholangiocarcinoma from
      January 2000 to December 2014 were retrospectively reviewed. Twenty-two patients
      who underwent R1 resection or had distant metastasis at the time of surgery were
      excluded. Using propensity score matching (matched factors: differentiation,
      lymphovascular invasion, perineural invasion, and T stage), the patients were
      divided into two groups: no dissection (n = 34) or lymph node dissection (n =
      34). Disease-free survival and overall survival were compared between groups.
      RESULTS: There was a marginally significant difference between the two groups
      with respect to the disease-free survival (no dissection vs. lymph node
      dissection: 20.0 [4.2-35.8] months vs. 64.0 [27.3-120.8] months, p = 0.077).
      Overall survival was significantly longer in the lymph node dissection group (no
      dissection vs. lymph node dissection: 44.0 [31.1-56.9] months vs. 90.0 [51.1
      158.9] months, p = 0.027). CONCLUSION: Radical surgery including an adequate
      lymph node dissection area and suitable harvested lymph nodes appears to improve
      oncologic outcomes for intrahepatic cholangiocarcinoma.

PMID- 30112703
TI  - Prognosis and Adherence with the National Comprehensive Cancer Network Guidelines
      of Patients with Biliary Tract Cancers: an Analysis of the National Cancer
      Database.
AB  - BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines recommend
      chemotherapy for patients with inoperable biliary tract cancers (BTC), as well as
      patients following resection of BTC with lymph node metastasis (N1)/positive
      margins (R1). We sought to define overall adherence, as well as long-term
      outcomes, with the NCCN guidelines for BTC using the National Cancer Database
      (NCDB). METHODS: A total of 176,536 patients diagnosed with BTC at a hospital
      participating in the NCDB between 2004 and 2015 were identified. RESULTS: Among
      all patients, 63% of patients received medical therapy (chemotherapy or best
      supportive care), 11% underwent surgical palliation, and 26% underwent curative
      intent surgery. According to the NCCN guidelines, 86% (n = 152,245) of patients
      were eligible for chemotherapy, yet, only 42.2% (n = 64,615) received
      chemotherapy. Factors associated with a lower adherence with NCCN guidelines
      included patient age (> 65 years: OR = 1.02), ethnicity (Black: OR = 1.14,
      Hispanic: OR = 1.21, Asian: OR = 1.24), and insurance status (non-private: OR =
      1.45, all p < 0.001). A smaller subset of patients was either recommended
      chemotherapy but refused (n = 9269, 10.6%) or had medical factors that
      contraindicated chemotherapy (n = 8275, 9.4%). On multivariable analysis,
      adjusting for clinical and tumor-specific factors, adherence with NCCN guidelines
      was associated with a survival benefit for patients receiving medical therapies
      (HR = 0.74) or undergoing curative-intent surgery (HR = 0.73, both p < 0.001).
      CONCLUSION: Less than half of patients with BTC received systemic chemotherapy in
      adherence with NCCN guidelines. While a subset of patients had contraindications
      or refused chemotherapy, other factors such as insurance status and ethnicity
      were associated with adherence. Adherence with chemotherapy guidelines may
      influence long-term outcomes.

PMID- 30112704
TI  - In vivo imaging of the immune response upon systemic RNA cancer vaccination by
      FDG-PET.
AB  - BACKGROUND: [18F]Fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG
      PET) is commonly used in the clinic for diagnosis of cancer and for follow-up of
      therapy outcome. Additional to the well-established value in tumor imaging, it
      bears potential to depict immune processes in modern immunotherapies. T cells
      enhance their glucose consumption upon activation and are crucial effectors for
      the success of such novel therapies. In this study, we analyzed the T cell
      immunity in spleen after antigen-specific stimulation of T cells via highly
      innovative RNA-based vaccines using FDG-PET/MRI. For this purpose, we employed
      systemic administration of RNA-lipoplexes encoding the endogenous antigen of
      Moloney murine leukemia virus (gp70) which have been previously shown to induce
      potent innate as well as adaptive immune mechanisms for cancer immunotherapy.
      Feasibility of clinical imaging of increased splenic FDG uptake was demonstrated
      in a melanoma patient participating in a clinical phase 1 trial of a tetravalent
      RNA-lipoplex cancer vaccine. RESULTS: We observed exclusive increase of glucose
      uptake in spleen compared to other organs thanks to liposome-mediated RNA
      targeting to this immune-relevant organ. In vivo and ex vivo FDG uptake analysis
      in the spleen of vaccinated mice correlated well with antigen-specific T cell
      activation. Moreover, the use of an irrelevant (antigen non-specific) RNA also
      resulted in enhanced FDG uptake early after vaccination through the activation of
      several other splenic cell populations. The glucose uptake was also dependent on
      the dose of RNA administered in line with the activation and frequencies of
      proliferating antigen-specific T cells as well as the general activation pattern
      of splenic cell populations. CONCLUSIONS: Our preclinical results show rapid and
      transient vaccination-induced increase of FDG uptake within the spleen reflecting
      immune activation preceding T cell proliferation. FDG-PET/CT in patients is also
      capable to image this immune activation resulting in a new potential application
      of FDG-PET/CT to image immune processes in new immunological therapies.

PMID- 30112705
TI  - Significant effect of group education in patients with diabetes type 1.
AB  - OBJECTIVE: Type 1 diabetes mellitus (T1DM) constitutes a real challenge in
      everyday practice for both physicians and patients. Due to the complexity of the
      disease and its unpredictable nature, structured education and training programs
      are nowadays implemented that ensure active patient involvement and self-care
      behaviors to achieve adequate glycemic control, prevent diabetic complications,
      and improve the quality of life of patients. These programs provide patients with
      the necessary knowledge and skills to self-monitor and self-manage the disease
      and its associated metabolic conditions. The aim of the study was to evaluate the
      effect of a structured 12-month education program that motivated patients to
      follow a healthy Mediterranean diet and exercise regularly as well as to adjust
      carbohydrate intake and insulin dose according to their needs. DESIGN: The
      education group (EG) was comprised of 62 patients (45 males) with type 1 DM, mean
      age 36 +/- 4.2 years and BMI 24.2 +/- 3.1 kg/m2. An age- and BMI-matched control
      group (CG, n = 25, mean age 41 +/- 6.4 years, BMI 25.7 +/- 4.2 kg/m2) was
      composed of patients referred but not enrolled in the project. RESULTS: At the
      end of this program, HbA1C levels were significantly decreased (8.5 +/- 2.1% vs.
      7.08 +/- 0.79%, p < 0.0001) as was also the incidence of hypoglycemic episodes (p
      < 0.05). Regarding daily glucose fluctuations, significant improvement (p < 0.05)
      was observed, as reflected in low, high, and daily median glucose values. On the
      other hand, the above parameters remained stable in the CG. CONCLUSIONS: These
      results strongly support the need for long-lasting structured education group
      courses for adult diabetic patients keen to change their habits in order to
      achieve self-management of the disease.

PMID- 30112706
TI  - Emerging EZH2 Inhibitors and Their Application in Lymphoma.
AB  - PURPOSE OF REVIEW: Enhancer of Zeste Homolog 2 (EZH2) is histone
      methyltransferase and catalyzes the methylation of histone 3 lysine 27, a mark of
      transcriptional repression. Various studies have elucidated the complex role of
      EZH2 in both normal biology and tumorigenesis. Here, we critically review the
      emerging role of EZH2 in malignancies, the development of small molecule
      inhibitors of EZH2, and their application in lymphoma. RECENT FINDINGS:
      Activating mutations and overexpression of EZH2 are found in non-Hodgkin lymphoma
      (NHL). As a result, several EZH2 inhibitors have been developed and entered
      clinical investigation. Tazemetostat, first-in-class EZH2 inhibitor, demonstrated
      enhanced clinical activity in mutant follicular lymphoma and diffuse large B cell
      lymphoma. With the early activity noted by tazemetostat in B cell lymphomas, the
      role of EZH2 inhibition in NHL is becoming more evident. This can be leveraged in
      future rationale combinations to enhance the activity of EZH2 inhibitors.

PMID- 30112709
TI  - Corrosion of 3D-Printed Orthopaedic Implant Materials.
AB  - 3D-printing technologies such as electron beam melting (EBM) have allowed for
      patient-specific orthopaedic implants, however differences generated from the
      fabrication process may alter the corrosion properties of Ti6Al4V implants. This
      study evaluated the corrosion characteristics of EBM-fabricated Ti6Al4V,
      alongside any linked microstructural and surface changes. EBM-fabricated Ti6Al4V
      and wrought Ti6Al4V specimens (n = 10 per group) underwent microstructural and
      surface characterisation before and after corrosion testing. Cyclic
      potentiodynamic polarisation of specimens was conducted in accordance with ASTM
      Standard F2129-17. The degree of corrosion damage was subsequently assessed via
      qualitative and quantitative measures. EBM-fabricated Ti6Al4V demonstrated a
      higher proportion of beta phases and greater surface roughness, compared to
      wrought Ti6Al4V. Significant differences were observed for all corrosion
      parameters between the two groups. The lower breakdown potentials (Eb) for EBM
      fabricated Ti6Al4V (2.035 V), compared to wrought Ti6Al4V (3.667 V), indicate a
      lower resistance to pitting corrosion. A greater resultant spread, and severity
      of corrosion damage was noted on wrought Ti6Al4V. An inferior in vitro corrosion
      resistance was observed for EBM-fabricated Ti6Al4V. Without post-processing, the
      rougher surface and differences in microstructure are likely to contribute to
      this. This suggests potential clinical implications upon in vivo implantation,
      although corrosion measures remain above recommended minimums.

PMID- 30112708
TI  - Comparison of 4D Flow MRI and Particle Image Velocimetry Using an In Vitro
      Carotid Bifurcation Model.
AB  - Four-dimensional (4D) Flow magnetic resonance imaging (MRI) enables the
      acquisition and assessment of complex hemodynamics in vivo from different
      vascular territories. This study investigated the viability of stereoscopic and
      tomographic particle image velocimetry (stereo- and tomo-PIV, respectively) as
      experimental validation techniques for 4D Flow MRI. The experiments were
      performed using continuous and pulsatile flows through an idealized carotid
      artery bifurcation model. Transverse and longitudinal planes were extracted from
      the acquired velocity data sets at different regions of interest and were
      analyzed with a point-by-point comparison. An overall root-mean-square error
      (RMSE) was calculated resulting in errors as low as 0.06 and 0.03 m/s when
      comparing 4D Flow MRI with stereo- and tomo-PIV, respectively. Quantitative
      agreement between techniques was determined by evaluating the relationship for
      individual velocity components and their magnitudes. These resulted in
      correlation coefficients (R2) of 4D Flow MRI with stereo- and tomo-PIV, as low as
      0.76 and 0.73, respectively. The 3D velocity measurements from PIV showed
      qualitative agreement when compared to 4D Flow MRI, especially with tomo-PIV due
      to the addition of volumetric velocity measurements. These results suggest that
      tomo-PIV can be used as a validation technique for 4D Flow MRI, serving as the
      basis for future validation protocols.

PMID- 30112707
TI  - Small-Molecule Inhibitors for the Treatment of Diffuse Large B Cell Lymphoma.
AB  - PURPOSE OF REVIEW: Diffuse large B cell lymphoma (DLBCL) remains the most common
      non-Hodgkin lymphoma (NHL) in developed countries. Up to 30-40% of patients
      experience either refractory or relapsed disease following receipt of front-line
      chemoimmunotherapy, and the majority of these patients will not be cured
      following receipt of subsequent therapy. RECENT FINDINGS: Small-molecule
      inhibitors (SMIs) are an attractive class of therapeutics for patients with
      chemorefractory DLBCL, and early-phase studies with these agents have typically
      demonstrated prolonged periods of disease control in responding patients without
      significant toxicity. Later-phase studies have investigated the combination of
      SMIs with cytotoxic agents in hopes that exposure to SMIs in the treatment course
      may improve outcomes for patients who would otherwise develop chemorefractory
      disease. SMIs appear to be effective in the treatment of DLBCL. A greater
      understanding of the molecular features of cases of DLBCL will allow for the more
      rational and presumably successful utilization of these targeted agents.

PMID- 30112711
TI  - Wearable Water Content Sensor Based on Ultrasound and Magnetic Sensing.
AB  - Fluid accumulation in the lower extremities is an early indicator of disease
      deterioration in cardiac failure, chronic venous insufficiency and lymphedema. At
      home wearable monitoring and early detection of fluid accumulation can
      potentially lead to prompt medical intervention and avoidance of hospitalization.
      Current methods of fluid accumulation monitoring either suffer from lack of
      specificity and sensitivity or are invasive and cost-prohibitive to use on a
      daily basis. Ultrasound velocity in animal and human tissue has been found to
      change with water content. However, previous prototype fluid monitoring sensors
      based on ultrasound are cumbersome and not wearable. Hence, in this research a
      compact water content sensor based on a wearable instrumented elastic band is
      proposed. A novel integration of magnetic sensing and ultrasonic sensing is
      utilized, where the magnetic sensor provides distance measurement and the
      ultrasonic sensor produces time-of-flight measurement. Magnetic field modeling
      with a Kalman filter and least squares linear fitting algorithms are employed to
      ensure robust sensor performance on a wearable device. The combination of the two
      measurements yields ultrasound velocity measurement in tissue. The water content
      sensor prototype was tested on a tissue phantom, on animal tissue and on a human
      leg. The error in velocity measurement is shown to be small enough for early
      detection of tissue edema.

PMID- 30112712
TI  - Apneic oxygenation during emergency airway management.

PMID- 30112710
TI  - Simulating Developmental Cardiac Morphology in Virtual Reality Using a Deformable
      Image Registration Approach.
AB  - While virtual reality (VR) has potential in enhancing cardiovascular diagnosis
      and treatment, prerequisite labor-intensive image segmentation remains an
      obstacle for seamlessly simulating 4-dimensional (4-D, 3-D + time) imaging data
      in an immersive, physiological VR environment. We applied deformable image
      registration (DIR) in conjunction with 3-D reconstruction and VR implementation
      to recapitulate developmental cardiac contractile function from light-sheet
      fluorescence microscopy (LSFM). This method addressed inconsistencies that would
      arise from independent segmentations of time-dependent data, thereby enabling the
      creation of a VR environment that fluently simulates cardiac morphological
      changes. By analyzing myocardial deformation at high spatiotemporal resolution,
      we interfaced quantitative computations with 4-D VR. We demonstrated that our
      LSFM-captured images, followed by DIR, yielded average dice similarity
      coefficients of 0.92 +/- 0.05 (n = 510) and 0.93 +/- 0.06 (n = 240) when compared
      to ground truth images obtained from Otsu thresholding and manual segmentation,
      respectively. The resulting VR environment simulates a wide-angle zoomed-in view
      of motion in live embryonic zebrafish hearts, in which the cardiac chambers are
      undergoing structural deformation throughout the cardiac cycle. Thus, this
      technique allows for an interactive micro-scale VR visualization of developmental
      cardiac morphology to enable high resolution simulation for both basic and
      clinical science.

PMID- 30112713
TI  - In reply: Apneic oxygenation during emergency airway management.

PMID- 30112714
TI  - Excellent Light Confinement of Hemiellipsoid- and Inverted Hemiellipsoid-Modified
      Semiconductor Nanowire Arrays.
AB  - In this paper, we introduce hemiellipsoid- and inverted hemiellipsoid-modified
      semiconductor nanowire (NW) optical structures, and present a systematic
      investigation on light management of the corresponding arrays based on GaAs. It
      is found that the modification makes well utilization of light scattering and
      antireflection, thus leading to excellent light confinement with limited
      effective thickness. For example, 90% and 95% of the incident photons with the
      energy larger than the bandgap energy can be trapped by the inverted
      hemiellipsoid-modified NW arrays with the effective thicknesses of only ~ 180 and
      270 nm, respectively. Moreover, excellent light confinement can be achieved in a
      broad range of the modification height. Compared to the corresponding array
      without top modification, spatial distribution of the photo-generated carriers is
      expanded, facilitating carrier collection especially for the planar pn junction
      configuration. Further investigation indicates that these composite
      nanostructures possess excellent omnidirectional light confinement, which is
      expected for advanced solar absorbers.

PMID- 30112715
TI  - Quality management initiatives-an instrument to turn also neurosurgery into a
      commodity?

PMID- 30112716
TI  - Comparing endoscopic and open decompression of the ulnar nerve in cubital tunnel
      syndrome: a prospective randomized study.
AB  - BACKGROUND: Prospective randomized data is currently lacking which compares
      endoscopically assisted surgery with open surgical techniques in the treatment of
      cubital tunnel syndrome (CUTS). The aim of this study is to compare patient
      outcome in both techniques. METHOD: This prospective study comprised of 45
      patients who, between October 2014 and February 2017, were randomly assigned to
      undergo either endoscopic or open surgery (22 and 23 patients respectively) for
      decompression of the ulnar nerve. Patients were followed up at 3 and 12 months
      postoperation. McGowan classification was used to determine the severity of
      symptoms. Surgical outcome was evaluated by Bishop classification. Pain levels
      were monitored according to gender from 0 to 10 days postoperation. Other factors
      investigated were chronic scar pain, working status, operation duration, and
      patient satisfaction regarding postoperative scarring and the procedure itself.
      RESULTS: Both methods are equally effective in the treatment of CUTS (Bishop
      score excellent or good 90% vs 96%). Postoperative pain is significant
      particularly in the first few days following surgery, but with no significant
      difference depending on procedure. In the open group, postoperative pain was
      significantly higher in women than in men; pain did not differ between the sexes
      in the endoscopic group. The tendency to lower levels of pain among
      endoscopically operated women in comparison with women in the open group was not
      statistically notable. Patients who underwent open decompression experienced
      notably higher levels of postoperative chronic scar pain. Although working status
      and satisfaction with the surgical outcome were the same in both groups,
      satisfaction with scarring was higher in the endoscopy group. Operation time was
      significantly longer by endoscopy. CONCLUSIONS: Both studied methods produced
      equal satisfactory outcomes in the treatment of CUTS. Endoscopy has the potential
      to minimize chronic scar pain and improve scarring esthetics, at the expense of
      longer operating time. CLINICAL TRIAL REGISTRATION NUMBER: Supported by Ministry
      of Health, Czech Republic-conceptual development of research organization
      (FNOs/2014, project number 20). Graphical abstract Median postoperative pain from
      0 to 10 days by group.

PMID- 30112718
TI  - Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for
      managing highly emetogenic chemotherapy in Southeast Asia: a multinational study.
AB  - PURPOSE: Recent studies suggested that olanzapine, together with dexamethasone
      and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing
      chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic
      chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA)
      countries where resources are limited. We aimed to evaluate the cost
      effectiveness of incorporating olanzapine into standard antiemetic regimens for
      the prevention of CINV in patients receiving HEC among SEA countries. METHODS:
      Using a decision tree model, clinical and economic outcomes associated with
      olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic
      regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in
      Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA +
      aprepitant) for CINV prevention following HEC were evaluated. This analysis was
      performed in Thailand, Malaysia, Indonesia, and Singapore, using societal
      perspective method with 5-day time horizon. Input parameters were derived from
      literature, network meta-analysis, government documents, and hospital databases.
      Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted
      life year (QALY) gained. A series of sensitivity analyses including probabilistic
      sensitivity analysis were also performed. RESULTS: Compared to doublet antiemetic
      regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026
      with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and
      Indonesia, respectively. Compared to triplet antiemetic regimen, switching
      aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD
      60.91 in Singapore. The probability of being cost-effective at a cost
      effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across
      countries. CONCLUSION: The use of olanzapine as part of standard antiemetic
      regimen is cost-effective for the prevention of CINV in patients receiving HEC in
      multiple SEA countries.

PMID- 30112717
TI  - Regulation of T cell immunity by cellular metabolism.
AB  - T cells are an important adaptive immune response arm that mediates cell-mediated
      immunity. T cell metabolism plays a central role in T cell activation,
      proliferation, differentiation, and effector function. Specific metabolic
      programs are tightly controlled to mediate T cell immune responses, and
      alterations in T cell metabolism may result in many immunological disorders. In
      this review, we will summarize the main T cell metabolic pathways and the
      important factors participating in T cell metabolic programming during T cell
      homeostasis, differentiation, and function.

PMID- 30112719
TI  - Inter-rater reliability of the Oral Assessment Guide for oral cancer patients
      between nurses and dental hygienists: the difficulties in objectively assessing
      oral health.
AB  - PURPOSE: Perioperative oral care is effective for the prevention and reduction of
      complications following surgery. However, oral cancer patients' oral health is
      often poor. During hospitalization, oral cancer patients frequently receive oral
      care from ward nurses as well as professional oral care from dental hygienists.
      Maintenance of good oral hygiene in these patients ideally requires cooperation
      between nurses and dental hygienists. Consequently, communication tools used to
      share information about the status of patients' oral health are needed. One such
      tool is the Oral Assessment Guide (OAG). However, the inter-rater reliability of
      the OAG has not been consistently reported; therefore, we examined this between
      nurses and dental hygienists. METHODS: Participants comprised 76 patients
      hospitalized for oral cancer treatment. After surgery, a nurse and a dental
      hygienist performed oral assessments using the OAG. Comparative statistical
      analyses were conducted to examine differences and consistencies in the scores of
      nurses and dental hygienists. RESULTS: Although almost all patients' oral health
      status was poor, none were given the worst score in the mucous membrane or
      gingiva categories. Further, the tongue, saliva, mucous membrane, gingiva, and
      teeth/denture categories had low kappa coefficients, indicating poor nurse-dental
      hygienist inter-rater reliability. In contrast, the kappa coefficients and
      agreement rates for voice and swallowing were high. Dental hygienists' scores
      were significantly higher for the tongue, gingiva, and teeth/denture categories
      than were nurses' scores. CONCLUSIONS: This study showed low nurse-dental
      hygienist inter-rater reliability for the OAG and highlighted the difficulties in
      objectively assessing patients' symptoms and oral health conditions. Therefore,
      rather than only relying on an objective assessment of symptoms by a clinician,
      assessments should also include patients' subjective reporting of symptoms. OAG
      will likely be used until a new assessment tool is developed. Objective
      assessment training and/or user manual development may be required to improve the
      reliability of OAG. The present training of one lesson a year is insufficient,
      and efforts should be made to improve this to get more reliable outcomes.

PMID- 30112720
TI  - Application of an early oral feeding protocol after pylorus-preserving
      pancreaticoduodenectomy.
AB  - PURPOSE: This study evaluates the effect of an enhanced recovery after surgery
      (ERAS)-based nutrition support protocol on oral intake and weight change in
      patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD).
      METHODS: A 14-day postoperative nutrition support protocol was developed to
      initiate oral intake after 1 week of enteral tube feeding and parenteral
      nutrition (early oral feeding, EOF). Forty-eight patients who underwent PPPD
      participated in the study (non-EOF, n = 23; EOF, n = 25). General information,
      nutrition supply route and amount, blood chemistry, and weight changes were
      tracked. RESULTS: The enteral tube feeding duration was 2.7 days shorter in the
      EOF group than in the non-EOF group. Furthermore, the EOF group started oral
      liquid and soft diets 1.1 and 2.5 days earlier than the non-EOF group,
      respectively. Compared with the non-EOF group, the EOF group reported a higher
      energy intake (22.1%; p = 0.001) and protein intake (17.4%; p = 0.000) via oral
      route. Although cumulative energy and protein intakes were similar in both
      groups, weight reduction in the EOF group (3.6 +/- 0.1%, 2.2 +/- 0.7 kg) was
      significantly less than the non-EOF group (8.2 +/- 0.9%, 5.2 +/- 0.5 kg). The
      blood levels of total protein and transferrin increased and prealbumin decreased,
      regardless of the EOF application. Serum albumin increased significantly only in
      the EOF group. CONCLUSION: The EOF protocol developed for post-PPPD patients
      enables the early initiation and increase in the amount of oral intake while
      significantly alleviating weight loss.

PMID- 30112721
TI  - Evaluation of stent placement for vena cava syndrome: phase II trial and phase
      III randomized controlled trial.
AB  - PURPOSE: Vena cava syndrome (VCS) from stenosis of the superior vena cava or
      inferior vena cava caused by compression from a malignant tumor is one of the
      typical clinical conditions in patients with advanced stage malignant disease.
      VCS is difficult to manage and painful, reducing patients' quality of life.
      Although several reports have investigated stent placement for VCS, this
      treatment has never been established as the standard because of the lack of
      evidence of the safety and efficacy. We conducted a phase II trial and a phase
      III randomized controlled trial to clarify the role of stent placement in
      managing patients with VCS. METHODS: In the phase II trial, 28 eligible patients
      were treated with stent placement. The efficacy of stent placement for VCS was
      evaluated based on the reduction of patients' symptom scores during 14 days
      following treatment. Technical success, technical feasibility, overall survival,
      recurrence of symptoms, and adverse events were evaluated. In the phase III
      trial, 32 patients were enrolled and randomly assigned to the test (n = 16) and
      control groups (n = 16). The area under the symptom score curve was compared
      between the groups. The EQ-5D, SF-8, and adverse events were evaluated until
      discontinuation of the protocol treatment or 28 days after enrollment. RESULTS:
      In the phase II trial, the median patients' symptom scores significantly
      decreased from 10.50 before the procedure to 3.00 after the procedure. Technical
      success and technical feasibility rates were 96.4% and 100%, respectively. The
      incidence of treatment-related grade 3 or higher adverse events was 14.3%. In the
      phase III trial, significant superiority of stent placement was observed in the
      test, compared to that in the control, group. There was no significant difference
      in most other evaluations between the groups. CONCLUSIONS: Stent placement
      significantly improved the symptoms of VCS; thus, it might be accepted as the
      standard treatment to manage the symptoms of VCS. TRIAL REGISTRATION: JIVROSG
      0402, JIVROSG-0807.

PMID- 30112722
TI  - Breast Cancer Collaborative Registry informs understanding of factors predicting
      sleep quality.
AB  - SIGNIFICANCE: Poor sleep quality is a common and persistent problem reported by
      women with breast cancer (BC). Empirical evidence identifies many risk factors
      for self-reported sleep deficiency, but inconsistencies limit translation to
      practice. PURPOSE: To increase understanding of risk factors predicting self
      reported poor sleep quality in women with BC who completed the Breast Cancer
      Collaborative Registry (BCCR) questionnaire. METHODS: This cross-sectional study
      recruited women with a first diagnosis of BC (n = 1302) at five sites in Nebraska
      and South Dakota. Women completed the BCCR that includes numerous variables as
      well as the Pittsburgh Sleep Quality Index (PSQI) and SF36v2 (n = 1260).
      Descriptive statistics and non-parametric correlations were used to determine
      associations and create predictive models of sleep quality with BCCR variables
      and SF36v2 subscales. RESULTS: Most women were white (93.7%) and married (71.5%);
      mean age was 60.1 (21-90) years. Poor sleep was self-reported by 53% of women.
      Seven variables were highly associated with sleep quality (p <= 0.001). The first
      model found younger age, lower physical activity, and higher fatigue were the
      strongest combined and independent variables predicting poor sleep quality (F =
      23.0 (p < .001), R2 = 0.103). Participants self-reported lower health status on
      most SF36v2 subscales [Z = 44.9 (11.6) to 49.1 (10.1)]. A second model found that
      all subscales were predictors of poor sleep; vitality, mental health, bodily
      pain, and general health were the strongest predictors (F = 101.3 (p < .001), R2
      = 0.26). CONCLUSIONS: Results confirm previously identified risk factors and
      reveal inconsistencies in other variables. Clinicians need to routinely screen
      for the identified risk factors of self-reported poor sleep quality.

PMID- 30112723
TI  - "...It might not have occurred to my husband that this woman, his wife who is
      taking care of him has some emotional needs as well...": the unheard voices of
      partners of Black African and Black Caribbean men with prostate cancer.
AB  - PURPOSE: Evidence suggests that partners of men with prostate cancer (CaP)
      experience greater psychosocial distress compared with men themselves. However,
      the experiences of partners of high-risk (1 in 4) Black African (BA) and Black
      Caribbean (BC) men with CaP remain poorly understood as existing research has
      predominantly focused on Caucasian populations. This study aimed to address this
      gap by exploring partners' experience and support needs as influenced both by the
      specific impacts of CaP, treatment side effects and socio-cultural context.
      METHODS: Using a constructivist grounded theory approach, eight face-to-face, two
      Skype and one telephone interviews were conducted with eligible partners (n =
      11). The interviews were analysed using constant comparison following key stages
      of open, focused and theoretical coding. RESULTS: Three broad categories emerged
      which described participants' experiences: 'partner in the passenger seat', 'care
      giving on an isolating journey', and 'coping as a partner'. Findings showed that
      BA and BC cultural marital context influenced how partners experienced and
      traversed the CaP journey. Peripheral involvement in decision-making,
      communication restrictions, limited access to support and lack of recognition for
      their experiences and needs further contributed to partners' psychological and
      emotional distress. CONCLUSIONS: Cultural beliefs, behaviours and values should
      be taken into account when developing psychosocial support for partners and their
      men with CaP. Specifically providing information focused on partners and
      including them in the CaP care pathway could help ensure that partners' needs are
      recognised and improve marital communications. This could potentially help
      partners and their men to identify acceptable ways of supporting each other
      throughout the CaP experience.

PMID- 30112724
TI  - Patients with head and neck cancer may need more intensive pain management to
      maintain daily functioning: a multi-center study.
AB  - PURPOSE: The purpose of this study is to investigate the prevalence of pain, pain
      management, and impact of recent pain on daily functioning in patients with head
      and neck cancer (HNC) and patients with other cancers. METHODS: This multi-center
      survey was conducted by using Brief Pain Inventory questionnaire to evaluate pain
      status and its impact on daily functioning. RESULTS: A total of 3289 patients
      were analyzed including 708 HNC patients and 2581 patients with other cancers.
      The overall pain prevalence was 69.17%. A higher percentage of HNC patients had
      recent pain (60.59 vs. 44.01%, P < 0.001), required pain management (86.29 vs.
      72.03%, P < 0.001), and used any analgesics (53.81 vs. 34.52%, P < 0.001). HNC
      patients with pain management had a higher prevalence of recent pain (85.83 vs.
      81.14%, P = 0.044) and a slightly lower satisfaction rate (74.00 vs. 79.70%, P =
      0.070). Regarding the impact of pain on daily functioning, HNC patients had a
      lower mean interference score for general activity such as walking, normal work,
      sleep, and life enjoyment. CONCLUSIONS: The HNC patients may need more intensive
      pain management to achieve optimal pain control and maintain daily functioning.

PMID- 30112725
TI  - Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with
      episodic migraine: an 8-week open-label extension study.
AB  - BACKGROUND: DFN-11, a 3 mg sumatriptan subcutaneous (SC) autoinjector for acute
      treatment of migraine, has not been assessed previously in multiple attacks. The
      objective of this study was to evaluate the efficacy, tolerability, and safety of
      DFN-11 in the acute treatment of multiple migraine attacks. METHODS: This was an
      8-week open-label extension of multicenter, randomized, double-blind, placebo
      controlled US study. Subjects averaging 2 to 6 episodic migraine attacks per
      month were randomized to DFN-11 or placebo to treat a single attack of moderate
      to-severe intensity and then entered the extension study to assess the efficacy,
      tolerability, and safety of DFN-11 in multiple attacks of any pain intensity.
      RESULTS: Overall, 234 subjects enrolled in the open-label period, and 29 (12.4%)
      discontinued early. A total of 848 migraine episodes were treated with 1042 doses
      of open-label DFN-11 and subjects treated a mean (SD) of 3.9 (2.3) attacks. At 2
      h postdose in attacks 1 (N = 216), 2 (N = 186), 3 (N = 142) and 4 (N = 110),
      respectively, pain freedom rates were 57.6%, 64.6%, 61.6%, and 66.3%; pain relief
      rates were 83.4%, 88.4%, 84.1%, and 81.7%; most bothersome symptom (MBS)-free
      rates were 69.0%, 76.5%, 77.7%, and 74.7%; nausea-free rates were 78.1%, 84.6%,
      86.5%, and 85.7%; photophobia-free rates were 75.3%, 76.4%, 72.3%, and 77.5%; and
      phonophobia-free rates were 75.2%, 77.5%, 73.6%, and 76.0%. Overall, 40.6%
      (89/219) of subjects reported treatment-emergent adverse events (TEAE), the most
      common of which were associated with the injection site: swelling (12.8%), pain
      (11.4%), irritation (6.4%), and bruising (6.4%). Most subjects (65.2%, 58/89) had
      mild TEAEs; severe TEAEs were reported by 1 subject (treatment-related jaw
      tightness). Five subjects (2.1%) discontinued due to adverse events, which
      included mild throat tightness (n = 2), moderate hernia pain (n = 1), moderate
      hypersensitivity (n = 1), and 1 subject with mild nausea and moderate injection
      site swelling. There were no serious TEAEs and no new or unexpected safety
      findings. CONCLUSION: DFN-11 was effective, tolerable, and safe in the acute
      treatment of 4 migraine attacks over 8 weeks, with consistent responses on pain
      and associated symptoms. Most TEAEs were mild, with a very low incidence of
      triptan-related TEAEs. DFN-11 is potentially an effective and safe alternative
      for the acute treatment of migraine. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02569853 . Registered 07 October 2015.

PMID- 30112727
TI  - Site-Specific Labeling of F-18 Proteins Using a Supplemented Cell-Free Protein
      Synthesis System and O-2-[18F]Fluoroethyl-L-Tyrosine: [18F]FET-HER2 Affibody
      Molecule.
AB  - PURPOSE: Although a preparation method for F-18-labeled proteins that used a cell
      free translation system and 4-[18F]fluoro-L-proline instead of L-proline has been
      reported, its introduction depends on amino acid sequences of target proteins.
      The purpose of the study was to propose site-specific labeling method of F-18 by
      using cell-free translation systems supplemented with an engineered orthogonal
      aminoacyl-tRNA synthetase derived from Methanocaldococcus jannaschii (pCNF
      RS)/suppressor tRNA (tRNACUAopt) pair, O-2-[18F]fluoroethyl-L-tyrosine
      ([18F]FET), and template DNA inserted with an amber codon. PROCEDURES: [18F]FET
      was prepared from the corresponding precursor and determined whether [18F]FET
      could be incorporated into an affibody molecule for human epidermal growth factor
      receptor type 2 (HER2; ZHER2:342) as the 21st amino acid used with the pCNF-RS
      tRNACUAopt pair and template DNA inserted with an amber codon in a cell-free
      translation system. Using SKOV-3 cells, we performed an in vitro binding assay of
      [18F]FET-ZHER2:342. Furthermore, in vivo positron emission tomography (PET)
      imaging in SKOV-3 xenograft-bearing mice was performed after the intravenous
      administration of [18F]FET-ZHER2:342. RESULTS: [18F]FET was successfully
      incorporated into proteins by using commercially available cell-free protein
      synthesis reagents with a pCNF-RS-tRNACUAopt pair and template DNA of the desired
      proteins inserted with an amber codon. The mean radiochemical yield (non-decay
      corrected) of [18F]FET-ZHER2:342 was 6.5 +/- 4.1 %. An in vitro cell binding
      assay revealed that SKOV-3 cells-bound [18F]FET-ZHER2:342 expressed HER2. The in
      vivo PET imaging in SKOV-3 xenograft-bearing mice revealed that [18F]FET
      ZHER2:342 accumulated in SKOV-3 xenografts. CONCLUSION: The method proposed in
      this study might be useful for preparing proteins with F-18 and molecular imaging
      in the preclinical development.

PMID- 30112726
TI  - Efficacy and safety of DFN-11 (sumatriptan injection, 3 mg) in adults with
      episodic migraine: a multicenter, randomized, double-blind, placebo-controlled
      study.
AB  - BACKGROUND: In a previous randomized, double-blind, proof-of-concept study in
      rapidly escalating migraine, a 3 mg dose of subcutaneous sumatriptan (DFN-11) was
      associated with fewer and shorter triptan sensations than a 6 mg dose. The
      primary objective of the study was to assess the efficacy and safety of acute
      treatment with DFN-11 compared with placebo in episodic migraine. METHODS: This
      was a multicenter, randomized, double-blind, placebo-controlled efficacy and
      safety study of DFN-11 in the acute treatment of adults with episodic migraine
      (study RESTOR). The primary endpoint was the proportion of subjects taking DFN-11
      who were pain free at 2 h postdose in the double-blind period compared with
      placebo. Secondary endpoints included earlier postdose timepoints, assessments of
      pain relief and subjects' freedom from their most bothersome symptom (MBS) (among
      nausea, photophobia, and phonophobia). Safety and tolerability were assessed.
      RESULTS: A total of 392 subjects was screened, 268 (68.4%) were randomized, and
      234 (87.3% of those randomized) completed the double-blind treatment period. The
      proportion of subjects who were pain free at 2 h postdose was significantly
      greater in the DFN-11 group than in the placebo group (51.0% vs 30.8%, P  = 
      0.0023). Compared with placebo, significantly higher proportions of subjects
      treated with DFN-11 were also pain free at 30, 60, and 90 min postdose (P  <= 
      0.0195). DFN-11 was significantly superior to placebo for pain relief at 60 min,
      90 min, and 2 h postdose (P <= 0.0179). At 2 h postdose, DFN-11 was also
      significantly superior to placebo for freedom from photophobia (P  =  0.0056) and
      phonophobia (P  =  0.0167). Overall, 33.3% (37/111) who received DFN-11 and 13.4%
      (16/119) who received placebo experienced at least 1 treatment-emergent adverse
      event (TEAE), the most common of which were injection site swelling (7.2% vs
      0.8%) and pain (7.2% vs 5.9%). Chest discomfort was about half as common in the
      DFN-11 treatment group as it was in the placebo group (0.9% vs 1.7%).
      CONCLUSIONS: This study met its primary endpoint, pain freedom at 2 h postdose,
      with DFN-11 significantly better than placebo, and the incidence of TEAEs and
      triptan sensations with DFN-11 was low. The 3 mg dose of sumatriptan in DFN-11
      appears to be an effective alternative to a 6 mg SC dose of sumatriptan, with
      good safety and tolerability. ( clinicaltrials.gov : NCT02569853; registered 07
      October 2015).

PMID- 30112728
TI  - A Critical Evaluation of Safety Signal Analysis Using Algorithmic Standardised
      MedDRA Queries.
AB  - INTRODUCTION: Algorithmic Standardised MedDRA(r) Queries (aSMQs) are increasingly
      used to enhance the efficiency of safety signal detection. The manner that aSMQs
      affect capture of potential safety cases is unclear. OBJECTIVES: Our objective
      was to characterise the performance of aSMQs with respect to their potential for
      double counting, the likelihood of events in aSMQ positive cases being clinically
      related, how frequently terms are used for algorithmically positive cases, and
      the face validity of positive cases based on the drug inducing events. We were
      also interested in what effect requiring symptoms to overlap temporally would
      have on performance. METHODS: We reviewed adverse event (AE) datasets of New Drug
      Applications and Biological License Applications and compiled a database
      including preferred terms and corresponding SMQs, SMQ term categories, AE start
      day, AE duration, drug name, and Anatomical Therapeutic Chemical class. Two
      reviewers independently determined if the algorithm was met and, if so, whether
      the broad terms overlapped temporally. RESULTS: A total of 107 marketing
      applications were reviewed, including 103,928 patients and 277,430 AEs. Use of
      algorithms condensed the number of AEs to between 5 and 8% and the incidence to
      about 1.5% relative to when the SMQs are used without the algorithm. Certain
      aSMQs exhibited a potential for overcounting. Requiring symptoms to temporally
      overlap helped to eliminate irrelevant cases. CONCLUSIONS: Our findings
      demonstrate that algorithmic and temporal assessment increased specificity of
      case retrieval, though the reduction in the number of terms or incidence seemed
      excessive for certain aSMQs. Evaluating the day of AE onset and duration improve
      specificity through identification of outlying events. Identification of drug
      classes known to cause the aSMQ's clinical condition provides face validity for
      this tool, yet detection of cases associated with novel classes may provide new
      understanding of these disorders. Improvements in some of the SMQ term lists may
      improve the performance of SMQs in general.

PMID- 30112729
TI  - Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Association with
      Commonly Prescribed Drugs in Outpatient Care Other than Anti-Epileptic Drugs and
      Antibiotics: A Population-Based Case-Control Study.
AB  - INTRODUCTION: Stevens-Johnson syndrome and toxic epidermal necrolysis have been
      associated with the use of various drugs, but evidence is scarce. We studied the
      association between new use of outpatient drugs other than anti-epileptic drugs
      and antibiotics and Stevens-Johnson syndrome and toxic epidermal necrolysis.
      METHODS: We conducted a matched (1:4) case-control analysis in 480 previously
      validated Stevens-Johnson syndrome/toxic epidermal necrolysis cases (1995-2013).
      We calculated odds ratios with 95% confidence intervals for Stevens-Johnson
      syndrome/toxic epidermal necrolysis in new users of drugs compared to non-users.
      For cases of Stevens-Johnson syndrome/toxic epidermal necrolysis diagnosed <= 84
      days after the first use of a drug, we assessed causality between drug exposure
      and Stevens-Johnson syndrome/toxic epidermal necrolysis using ALDEN (algorithm of
      drug causality in epidermal necrolysis). We calculated absolute risks by dividing
      the number of Stevens-Johnson syndrome/toxic epidermal necrolysis cases <= 84
      days after new drug exposure by the total number of new users of the drug.
      RESULTS: There was an association between Stevens-Johnson syndrome/toxic
      epidermal necrolysis and the use of allopurinol (odds ratio 24.51, 95% confidence
      interval 2.94-204.04) and cyclooxygenase-2 inhibitors (odds ratio 24.19, 95%
      confidence interval 2.91-200.92). Proton pump inhibitors, fluoxetine,
      mirtazapine, and 5-aminosalicylates (sulfasalazine, mesalamine) were also
      associated with an increased risk of Stevens-Johnson syndrome/toxic epidermal
      necrolysis, though with lower odds ratios. ALDEN score application suggests a
      likely causality for these associations. Absolute risks of Stevens-Johnson
      syndrome/toxic epidermal necrolysis were 6.0/100,000 new users for allopurinol,
      and 1.9-4.3/100,000 new users for cyclooxygenase-2 inhibitors and 5
      aminosalicylates, and 0.2-1.6/100,000 new users for proton pump inhibitors,
      fluoxetine, and mirtazapine. We found no association between Stevens-Johnson
      syndrome/toxic epidermal necrolysis and oxicams, benzodiazepines, citalopram,
      sertraline, paroxetine, venlafaxine, and phosphodiesterase-5 inhibitors despite >
      100,000 new users. CONCLUSIONS: In this observational study, we observed likely
      causal associations between Stevens-Johnson syndrome/toxic epidermal necrolysis
      and use of allopurinol, cyclooxygenase-2 inhibitors, and 5-aminosalicylates, and
      potential associations for proton pump inhibitors, fluoxetine, and mirtazapine.

PMID- 30112730
TI  - Reduced Contact Resistance Between Metal and n-Ge by Insertion of ZnO with Argon
      Plasma Treatment.
AB  - We investigate the metal-insulator-semiconductor contacts on n-Ge utilizing a ZnO
      interfacial layer (IL) to overcome the Fermi-level pinning (FLP) effect at
      metal/Ge interface and reduce the barrier height for electrons. A small
      conduction band offset of 0.22 eV at the interface between ZnO and n-Ge is
      obtained, and the ZnO IL leads to the significant reduced contact resistance (Rc)
      in metal/ZnO/n-Ge compared to the control device without ZnO, due to the
      elimination of FLP. It is observed that the argon (Ar) plasma treatment of ZnO
      can further improve the Rc characteristics in Al/ZnO/n-Ge device, which is due to
      that Ar plasma treatment increases the concentration of oxygen vacancy Vo, acting
      as n-type dopants in ZnO. The ohmic contact is demonstrated in the Al/ZnO/n-Ge
      with a dopant concentration of 3 * 1016 cm-3 in Ge. On the heavily doped n+-Ge
      with a phosphor ion (P+) implantation, a specific contact resistivity of 2.86 *
      10- 5 Omega cm2 is achieved in Al/ZnO/n+-Ge with Ar plasma treatment.

PMID- 30112731
TI  - Substitution of fresh forage ramie for alfalfa hay in diets affects production
      performance, milk composition, and serum parameters of dairy cows.
AB  - We hypothesized that ramie, Boehmeria nivea (a nettle native to Asia), can be
      used as a high-quality forage to replace alfalfa hay in diets of dairy cows.
      Accordingly, we aimed to examine the effects of substituting fresh forage ramie
      for alfalfa (Medicago sativa) hay on production performance, milk composition,
      and serum parameters of dairy cows. Thirty-two Holstein cows (body weight (BW) =
      590 +/- 50.6 kg) were randomly divided into four groups of eight cows. The
      experimental period lasted 10 weeks. The dietary treatments consisted of four
      proportions of fresh forage ramie (0, 33, 67, and 100%) as a substitute for
      alfalfa hay (designated as CON, FR33, FR67, and FR100, respectively). On days 69
      and 70 of the experimental period, milk and blood samples were collected for
      analysis. We found no significant differences in the milk yield and milk quality
      (milk protein percentage, milk fat percentage, and milk lactose percentage)
      between the treatments. We did find that forage ramie significantly reduced dry
      matter intake (DMI) and 4% fat-corrected milk (FCM) yield. Meanwhile, no
      significant differences were detected in serum parameters between the treatments,
      with the exception of triglyceride (TG) and alanine aminotransferase (ALT). In
      conclusion, our data indicate that alfalfa hay can be replaced with forage ramie
      in the diet of Holstein cows in the milk lactation stage, with no negative
      effects on milk quality and blood parameters.

PMID- 30112732
TI  - Seroprevalence and risk factors associated with bovine viral diarrhea virus and
      bovine herpes virus-1 in Zanjan Province, Iran.
AB  - Bovine viral diarrhea virus (BVDV) and bovine herpes virus-1 (BHV-1) remain as
      the major pathogens with heavy economic consequences in Iran. The prevalence of
      antibodies against BVDV and BHV-1, the rate of BVDV persistently infected (PI)
      animals, and associated risk factors were evaluated in a cross-sectional study
      carried out in Zanjan Province, Northwest Iran, in December 2011. A total number
      of 562 cattle in 10 herds and five cities were randomly selected, and their serum
      samples were tested to detect antibodies to these viruses and also BVDV antigen
      positive (PI) animals. The data were analyzed with Pearson's correlation
      coefficient, chi-square, and logistic regression test. In total, nine and eight
      of the selected herds were seropositive to BVDV and BHV-1, respectively. The
      overall seroprevalence of these infections were estimated at 28.6 and 10.7% for
      BVDV and BHV-1, respectively, and 0.53% of the samples were detected as
      persistently infected. Statistical analysis revealed that sex, age, and farming
      system are risk factors for both infections (P < 0.05), while breed was
      determined as a strong risk factor only for BVDV (P < 0.001). In addition, the
      present study certainly identifies that infection with BVDV is associated with
      infection to BHV-1 (OR = 4.52, 95% CI: 2.60-7.80; P ? 0.001). The results add our
      knowledge about the prevalence and associated risk factors of BVDV and BHV-1 in
      Iran and imply that the prophylactic and surveillance strategies need to be
      implemented to reduce the risk of spread of these viruses.

PMID- 30112733
TI  - Assessing the comparative advantage of broiler production in Peninsular Malaysia
      using policy analysis matrix.
AB  - Broiler meat is the largest and cheapest protein source in Malaysia. Using the
      policy analysis matrix (PAM), this study examines the comparative advantage of
      broiler production in Peninsular Malaysia. Three hundred and ten farms in
      Peninsular Malaysia were involved in a field survey. The results of the domestic
      resource cost (DRC) show that Malaysia has a comparative advantage in all scales
      of broiler production. Sensitivity analysis indicates that the changes in input
      prices have a significant effect on comparative advantage. Nonetheless, the
      industry should reduce its dependence on corn-based feed, which is expensive and
      has an unstable price, to increase competitiveness in further securing its
      comparative advantage.

PMID- 30112734
TI  - The potential of small ruminant farming as a means of poverty alleviation in
      rural southern India.
AB  - Small ruminant production has the potential to address the global challenge of
      greatly increased food production in impoverished rural areas in a manner that is
      socioeconomically sustainable and carbon efficient. Twenty-six small ruminant
      landless farmers in three villages in the Kanchipuram District of the state of
      Tamil Nadu were surveyed with regard to their sheep farming practice and
      production indices, with the preliminary aim of evaluating the potential of small
      ruminant farming in alleviating poverty in parts of rural in southern India. The
      small ruminant farmers reared mostly indigenous Madras Red sheep as a means of
      generating primary or supplementary income. Participatory interviews were
      undertaken to enable the completion of a questionnaire pertaining to sheep
      production over the four most recent annual production cycles (referred to as
      instances) at the time of the study. When calculating the annual farm profits
      without taking into consideration the opportunity cost of labour, 83% of annual
      sheep production cycles over a 4-year period added to household incomes. Further,
      23% of the instances that accounted for the opportunity cost of labour, household
      income was raised above the Indian Government's defined poverty line solely
      through small ruminant farming. Management practices were identified, while
      participating in landless farmer interviews provided an insight into the
      husbandry, or lack thereof, which resulted in low lambing percentages and rates
      of high ewe losses, perinatal lamb mortality and abortion. The study showed both
      the vulnerability and potential resilience of small ruminant farming to natural
      disaster, in this case catastrophic flooding in 2015. While small ruminant
      farming generated income in most instances, the way it is practiced creates
      opportunities for simple changes in husbandry and management that could make it
      more efficient in poverty alleviation.

PMID- 30112735
TI  - The African Sepsis Alliance: making a difference in the fight against sepsis in
      Africa.

PMID- 30112736
TI  - Interprofessional Collaborative Practice in the Medical Intensive Care Unit: a
      Survey of Caregivers' Perspectives.
AB  - BACKGROUND: Research on caregivers, defined as designated family members or
      support persons, in the medical intensive care unit (MICU) has primarily focused
      on their emotional needs and experiences, thus leaving a gap in knowledge related
      to their perceptions of team dynamics. OBJECTIVE: To examine caregivers'
      perceptions of team interactions and competencies for interprofessional
      collaborative practice (IPCP) and overall satisfaction with the MICU team.
      METHODS: The Support Person Jefferson Teamwork Observation Guide (JTOG)TM was
      administered to a convenience sample of caregivers in the MICU at a large urban
      academic medical center between May 2016 and December 2016. RESULTS: One hundred
      sixty-one JTOG surveys were completed. Caregivers agreed on the importance of
      healthcare professionals working together as a team to provide patient care (3.97
      out of 4.0 on Likert response scale where 1 is "Not at all important" and 4 is
      'Extremely important") and were satisfied with the MICU team (3.74 out of 4.0),
      positively evaluating the four core competencies for IPCP (3.55 for
      values/ethics, 3.58 for interprofessional communication, 3.61 for
      roles/responsibilities, and 3.64 for teams/teamwork) and the patient/family
      centeredness sub-competency (3.58 out of 4.0). There was a strong positive
      correlation between caregivers' Global JTOG scores and overall satisfaction with
      the MICU team (r = 0.596, p < 0.01). Caregivers' comments about factors that
      affected their experience focused on aspects of interprofessional communication
      and patient/family-centeredness. CONCLUSION: Findings underscore the importance
      of interprofessional communication and providing patient/family-centered care.
      Assessing caregivers' perceptions of IPCP can provide a critical lens into team
      functioning and, thus, be used to identify teams' strengths as well as
      opportunities for improvement.

PMID- 30112738
TI  - Pie Crust Technique of the Deep Medial Collateral Ligament in Knee Arthroscopy:
      Ultrasound and Anatomic Study.
AB  - This article determines compartment opening of the medial articular space of the
      knee after pie crust (PC) technique of the medial collateral ligament (MCL) by
      ultrasound measurements and anatomic dissection. This is a cadaveric study of 12
      specimens. Four anatomic references were marked on the skin. Distances between
      the femur and tibia in the internal compartment at 30 degrees of flexion were
      obtained with ultrasound measurements in four situations: with and without
      applying valgus force both prior and after the PC technique. Ultrasound
      measurements of the medial articular compartment were made twice and mean value
      was calculated. An anatomical dissection was performed and distances between the
      puncture marks and the infrapatellar branch of the saphenous nerve was measured.
      Lilliefors test of normality was applied and variables were expressed as mean and
      standard deviation (SD). Qualitative variables were expressed by absolute
      frequencies and percentages. Statistical significance was a two-tailed p-value of
      < 0.05. Prior to the PC technique, mean (SD) distance between the femur and tibia
      in the medial compartment were 14.2 (4.0) mm in basal conditions and 17.1 (3.7)
      mm when applying valgus force (p = 0.003). PC technique increased the mean (SD)
      distance by 1.9 (1.9) mm under basal conditions (p < 0.01) and 2.9 (1.6) mm when
      applying valgus force (p < 0.01). The infrapatellar branches of the saphenous
      nerve were not damaged and the mean (SD) distance between the punctures and the
      nerve was 9.0 (3.3) mm. The PC is a reproducible, safe, and measurable surgical
      technique that opens controllably the medial compartment. PC as described avoided
      damage to the nerve branches.

PMID- 30112737
TI  - Patterns of Use and Correlates of Patient Satisfaction with a Large Nationwide
      Direct to Consumer Telemedicine Service.
AB  - BACKGROUND: Despite its rapid expansion, little is known about use of direct to
      consumer (DTC) telemedicine. OBJECTIVE: To characterize telemedicine patients and
      physicians and correlates of patient satisfaction DESIGN: Cross-sectional study
      PARTICIPANTS: Patients and physicians of a large nationwide DTC telemedicine
      service MAIN MEASURES: Patient characteristics included demographics and whether
      or not they reported insurance information. Physician characteristics included
      specialty, board certification, and domestic versus international medical
      training. Encounter characteristics included time of day, wait time, length,
      coupon use for free or reduced-cost care, diagnostic outcome, prescription
      receipt, and patient/physician geographic concordance. Patients rated
      satisfaction with physicians on scales of 0 to 5 stars and reported where they
      would have sought care had they not used telemedicine. Logistic regression was
      used to assess factors associated with 5-star physician ratings. KEY RESULTS: The
      analysis included 28,222 encounters between 24,040 patients and 277 physicians
      completed between January 2013 and August 2016. Sixty-five percent of patients
      were under 40 years and 32% did not report insurance information. Family medicine
      was the most common physician specialty (47%) and 16% trained at a non-US medical
      school. Coupons were used in 24% of encounters. Respiratory infections were
      diagnosed in 35% of encounters and 69% resulted in a prescription. Had they not
      used telemedicine, 43% of patients reported they would have used urgent
      care/retail clinic, 29% would have gone to the doctor's office, 15% would have
      done nothing, and 6% would have gone to the emergency department. Eighty-five
      percent of patients rated their physician 5 stars. High satisfaction was
      positively correlated with prescription receipt (OR 2.98; 95%CI 2.74-3.23) and
      coupon use (OR 1.47; 95%CI 1.33-1.62). CONCLUSIONS: Patients were largely
      satisfied with DTC telemedicine, yet satisfaction varied by coupon use and
      prescription receipt. The impact of telemedicine on primary care and emergency
      department use is likely to be small under present usage patterns.

PMID- 30112739
TI  - Does the Robotic Arm and Preoperative CT Planning Help with 3D Intraoperative
      Total Knee Arthroplasty Planning?
AB  - Although several studies highlight the advantages of robotic arm-assisted total
      knee arthroplasty (RA-TKA), few investigate its intraoperative outcome.
      Therefore, the purpose of this study was to analyze the RA-TKA's ability to
      assist with intraoperative correction of: (1) flexion and (2) extension gaps, as
      well as its ability to (3) accurately predict implant sizes. Additionally, in
      this RA-TKA cohort, length of stay, complications, and readmissions were
      assessed. A total of 335 patients who underwent RA-TKA were included. The robotic
      software virtually measured the intraoperative prebone cut extension and flexion
      gaps. Differences in medial versus lateral prebone cut extension and flexion gaps
      were calculated. A total of 155 patients (46%) had an extension gap difference of
      between -2 and 2 mm (mean, -0.3 mm), while 119 patients (36%) had a flexion gap
      difference of between -2 and 2 mm (mean, -0.6 mm). Postbone cut differences in
      medial versus lateral flexion and extension gaps were measured. Balanced knees
      were considered to have a medial and lateral flexion gap difference within 2 mm.
      The robot-predicted implant size was also compared with the final implant size.
      Additionally, lengths of stay, complications, and readmissions were assessed. All
      patients achieved a postbone cut extension gap difference between -1 and 1 mm
      (mean, -0.1 mm). A total of 332 patients (99%) achieved a postbone cut flexion
      gap difference of between -2 and 2 mm (mean, 0 mm). For 98% of prostheses, the
      robotic software predicted within 1 implant size the actual tibial or femoral
      implant size used.The mean length of stay was found to be 2 days. No patients
      suffered from superficial skin infection, pin site infections or fractures, soft
      tissue damage, and no robotic cases were converted to manual TKA due to
      intraoperative complications. A total of 8 patients (2.2%) were readmitted;
      however, none were directly related to robotic use. The robotic software and use
      of a preoperative computed tomography (CT) substantially helped with
      intraoperative planning and accurate prediction of implant sizes. Therefore,
      based on the results of this study, the RA-TKA device does, in fact, provide
      considerable intraoperative assistance.

PMID- 30112740
TI  - Acquired Haemophilia A Associated with Subsequent Hepatocellular Carcinoma.
AB  - Acquired haemophilia A (AHA) is a rare autoimmune disease caused by antibodies
      directed against clotting factor VIII. About half of cases are idiopathic, but
      AHA may also be secondary to autoimmune, dermatologic, or oncologic diseases. In
      approximately 10% of non-idiopathic cases, the disease occurs after or with the
      diagnosis of cancer as an extremely rare paraneoplastic syndrome. We describe the
      case of a 73-year-old male patient diagnosed with AHA and successfully treated
      with recombinant human activated factor VIIa and immunosuppression. Two and a
      half years later, however, the disease relapsed and a routine ultrasound revealed
      a liver tumour that was then diagnosed as hepatocellular carcinoma. We present
      this case to increase awareness that this life-threatening condition may develop
      years prior to the diagnosis of cancer.

PMID- 30112743
TI  - Surgery for Pediatric Ureteropelvic Junction Obstruction-Comparison of Outcomes
      in Relation to Surgical Technique and Operating Discipline in Germany.
AB  - INTRODUCTION:  Surgery for ureteropelvic junction obstruction (UPJO) is performed
      by both pediatric surgeons (PS) and urologists (URO). The aim of this study was
      to analyze treatment modalities for UPJO and results in relation to the surgical
      technique and the operating discipline in Germany. MATERIAL AND METHODS:  Data of
      patients aged 0 to 18 years were extracted from a major public health insurance
      (covering ~5.7 million clients) during 2009 to 2016 and were analyzed for
      sociodemographic variables, surgical technique, and treating discipline. Logistic
      regression analysis was performed for the risk of a complication within the first
      postoperative year. RESULTS:  A total of 229 children (31.0% female) were
      included. Laparoscopic pyeloplasty (LP) was performed in 58 (25.3%) patients (8.6
      +/- 6.4 years), and open pyeloplasty (OP) was applied in 171 (74.7%; 4.6 +/- 5.9
      years). LP was the dominant technique in females (p < 0.02); males preferentially
      underwent OP (p < 0.02). Length of hospital stay was 4.3 days (p = 0.0005)
      shorter in LP compared with that in OP, especially in children <= 2 years (6.7
      days, p = 0.007). PS operated on 162 children (70.7%), and URO performed surgery
      on 67 patients (29.3%). The mean age of children operated by PS (3.5 +/- 4.7
      years) was significantly younger compared with that operated by URO (10.8 +/- 6.5
      years, p < 0.0001). Complication rates were independent of surgical technique or
      treating specialty. CONCLUSION:  In Germany, UPJO was treated by LP in 25.3% of
      patients, which was associated with a shorter length of stay, especially in
      children <= 2 years. Complication rates were independent of the operating
      specialty and surgical technique. Therefore, LP should be further promoted for
      the treatment of UPJO in small children.

PMID- 30112742
TI  - Adoption of Electronic Dental Records: Examining the Influence of Practice
      Characteristics on Adoption in One State.
AB  - OBJECTIVE:  Compared with medicine, less research has focused on adoption rates
      and factors contributing to the adoption of electronic dental records (EDRs) and
      certified electronic health records (EHRs) in the field of dentistry. We ran two
      multivariate models on EDR adoption and certification-capable EHR adoption to
      determine environmental and organizational factors associated with adoption.
      METHODS:  We conducted telephone survey of a 10-item questionnaire using
      disproportionate stratified sampling procedure of 149 dental clinics in Tennessee
      in 2017 measuring adoption of dental information technology (IT) (EDRs and
      certification-capable EHRs) and practice characteristics, including region,
      rurality, specialty, and practice size. We used binomial logistic regression
      models to determine associations of adoption with predictor variables. RESULTS: 
      A total of 77% of surveyed dental clinics in Tennessee had adopted some type of
      EDR system. When the definitions of certification capable were applied, the
      adoption rates in dental clinics dropped to 58%. A binomial logistic regression
      model for the effects of rurality, specialization, and practice size on the
      likelihood that a clinic would adopt an EHR product was statistically significant
      (chi-square (3) = 12.41, p = 0.0061). Of the three predictor variables,
      specialization and practice size were significant: Odds of adopting an EHR is 67%
      lower for specialists than for general dentists; and clinics with two or more
      practicing dentists were associated with a much greater likelihood of adopting an
      EHR-capable system (adjusted odds ratio = 3.09, p = 0.009). CONCLUSION:  Findings
      from this study indicate moderate to high levels of overall dental IT adoption.
      However, adoption rates in dental clinics do remain lower than those observed in
      office-based physician practices in medicine. Specialization and practice size
      were significant predictors of EHR-capable system adoption. Efforts to increase
      EHR adoption in dentistry should be mindful of potential disparities in smaller
      practices and between dental specialties and generalists.

PMID- 30112744
TI  - Cardiogenic Necrotizing Enterocolitis: A Clinically Distinct Entity from
      Classical Necrotizing Enterocolitis.
AB  - AIM:  The main purpose of this study was to investigate if necrotizing
      enterocolitis (NEC) has a different presentation and outcome in patients with
      congenital heart defect (CHD) (cardiogenic NEC) from those without (classical
      NEC). MATERIALS AND METHODS:  A systematic review of the literature on the
      characteristics of infants with NEC and CHD was performed by three independent
      investigators using a defined strategy (PubMed, Cochrane, Embase, and Web of
      Science). A meta-analysis was conducted on studies comparing NEC in infants with
      CHD and non-CHD infants using RevMan 5.3. RESULTS:  Systematic review: Of 7,291
      abstracts screened, 126 full-text articles were analyzed and 51 studies were
      included. NEC had an incidence of 5.1% in CHD infants (7,728/151,046, range 0
      24%) and 0.8% in non-CHD infants (26,430/3,256,891, range 0.1-8.9%; p < 0.0001).
      In very low birth weight infants, NEC occurred in 6.3% of CHD patients
      (6,361/100,454pts) and in 8.9% of non-CHD (23,201/257,794pts; p < 0.0001). In CHD
      cases, NEC occurred before cardiac surgery in 48% cases and surgery for NEC was
      required in 31% infants (2,037/6,683). Meta-analysis: In eight comparative
      studies, the incidence of NEC was higher in CHD infants (6%, 768/13,145) than in
      infants with no CHD (0.9%, 32,625/3,354,323pts; p < 0.00001, odds ratio [OR]
      1.84, 95% confidence interval [CI] 1.7-1.9). The overall mortality was higher in
      infants with CHD and NEC (38%, 243/640) than in those without CHD (27%,
      6651/24810; p < 0.00001, OR 3.4, 95% CI 2.8-4.1). CONCLUSION:  This is the first
      evidence-based study showing that infants with cardiogenic NEC have different
      demographics and outcomes than those with classical NEC. The risk of developing
      NEC and the mortality rate are higher among infants with CHD than in those
      without. Conversely, the need for intestinal surgery is lower in babies with
      cardiogenic NEC than in those with classical NEC. Further studies are needed to
      establish preventative and management interventions that are specific to infants
      with or at risk of developing cardiogenic NEC.

PMID- 30112745
TI  - European Paediatric Surgeons' Association Survey on the Management of Pediatric
      Appendicitis.
AB  - AIM:  To define patterns in the management of pediatric appendicitis. METHODS:  A
      total of 169 delegates from 42 (24 European) countries completed a validated
      survey administered at the EUPSA 2017 annual congress. RESULTS:  In the work-up
      of children with suspected acute appendicitis, most surgeons rely on full blood
      count (92%), C-reactive protein (82%), and abdominal ultrasonography (76%), but
      rarely on computed tomography scans or magnetic resonance imaging. In suspected
      simple appendicitis, most surgeons (76%) do not perform appendectomy at night in
      clinically stable patients and start antibiotic preoperatively (64%), but only
      15% offer antibiotic therapy alone (no appendectomy). In suspected perforated
      appendicitis, 96% start antibiotic preoperatively, and 92% perform an
      appendectomy. Presence of phlegmon/abscess is the main contraindication to
      immediate surgery. In case of appendix mass, most responders (75%) favor a
      conservative approach and perform interval appendectomy always (56%) or in
      selected cases (38%) between 2 and 6 months from the first episode (81%).
      Children with large intraperitoneal abscesses are managed by percutaneous
      drainage (59% responders) and by surgery (37% responders). Laparoscopy is the
      preferred surgical approach for both simple (89%) and perforated appendicitis
      (81%). Most surgeons send the appendix for histology (96%) and pus for
      microbiology, if present (78%). At the end of the operation, 58% irrigate the
      abdominal cavity only if contaminated using saline solution (93%). In selected
      cases, 52% leave a drain in situ. CONCLUSION:  Some aspects of appendicitis
      management lack consensus, particularly appendix mass and intraperitoneal
      abscess. Evidence-based guidelines should be developed, which may help
      standardize care and improve clinical outcomes.

PMID- 30112741
TI  - A Systematic Review of the Technology Acceptance Model in Health Informatics.
AB  - BACKGROUND:  One common model utilized to understand clinical staff and patients'
      technology adoption is the technology acceptance model (TAM). OBJECTIVE:  This
      article reviews published research on TAM use in health information systems
      development and implementation with regard to application areas and model
      extensions after its initial introduction. METHOD:  An electronic literature
      search supplemented by citation searching was conducted on February 2017 of the
      Web of Science, PubMed, and Scopus databases, yielding a total of 492 references.
      Upon eliminating duplicates and applying inclusion and exclusion criteria, 134
      articles were retained. These articles were appraised and divided into three
      categories according to research topic: studies using the original TAM, studies
      using an extended TAM, and acceptance model comparisons including the TAM.
      RESULTS:  The review identified three main information and communication
      technology (ICT) application areas for the TAM in health services: telemedicine,
      electronic health records, and mobile applications. The original TAM was found to
      have been extended to fit dynamic health service environments by integration of
      components from theoretical frameworks such as the theory of planned behavior and
      unified theory of acceptance and use of technology, as well as by adding
      variables in specific contextual settings. These variables frequently reflected
      the concepts subjective norm and self-efficacy, but also compatibility,
      experience, training, anxiety, habit, and facilitators were considered.
      CONCLUSION:  Telemedicine applications were between 1999 and 2017, the ICT
      application area most frequently studied using the TAM, implying that acceptance
      of this technology was a major challenge when exploiting ICT to develop health
      service organizations during this period. A majority of the reviewed articles
      reported extensions of the original TAM, suggesting that no optimal TAM version
      for use in health services has been established. Although the review results
      indicate a continuous progress, there are still areas that can be expanded and
      improved to increase the predictive performance of the TAM.

PMID- 30112746
TI  - Current Options for the Treatment of Pectus Carinatum: When to Brace and When to
      Operate?
AB  - Pectus carinatum has traditionally been described as a rare chest wall anomaly in
      comparison to pectus excavatum. However, recent data from chest wall anomaly
      clinics demonstrate that this deformity is probably much more frequent than once
      believed. In the past, invasive surgical correction by the Ravitch technique was
      essentially the only option for treatment of pectus carinatum. Major advances
      over the past two decades have provided additional options, including noninvasive
      chest wall bracing and minimally invasive surgical correction. This article will
      discuss current options for the treatment of pectus carinatum, and some of the
      factors that should be taken into account when choosing the options available.
      Diagnosis and treatment of the pectus arcuatum variant will also be described.

PMID- 30112747
TI  - Deformities of the Thoracic Wall: Don't Forget the Plastic Surgeon.
AB  - Surgical procedures for pectus excavatum (PE) repair, such as minimally invasive
      repair of pectus excavatum or similar interventions (modified open
      videoendoscopically assisted repair of pectus excavatum), for remodeling the
      anterior thoracic wall may finally not always achieve sufficiently pleasing
      aesthetic results. Particularly in the asymmetric and polymorphic cases, remnant
      deformities may still be present after any sophisticated remodeling attempt. On
      the other hand, some cases despite optimal surgical management develop mild
      recurrences with partial concavity or rib cartilage distortion shortly after
      pectus-bar removal. Secondary treatment options then may include open access
      surgery, resection, or reshaping of deformed and prominent costal cartilage.
      Residual concave areas can be filled by autologous tissue, such as cartilage
      chips, liposhifting, or implantation of customized alloplastics. To provide the
      best options for a variety of primary or secondary postsurgical expressions of
      anterior wall deformities, any physician dealing with PE corrections should be
      familiar with various shaping and complementary reconstructive techniques or at
      least should have knowledge of such. However, among treating surgeons, there is
      an awareness that no single method can be applied for every kind of funnel chest
      deformity. Careful selection of appropriate techniques, either as a single
      approach for the ordinary deformities or in conjunction with ancillary procedures
      for the intricate cases, should be mandatory, based on the heterogeneity of
      symptoms, severity, expectations, and surgical and technical resources. A variety
      of such ancillary reconstructive procedures for PE repair are explained and
      illustrated herewith.

PMID- 30112748
TI  - State of Play: Eight Decades of Surgery for Esophageal Atresia.
AB  - AIM:  Surgical expertise and advances in technical equipment and perioperative
      management have led to enormous progress in survival and morbidity of patients
      with esophageal atresia (EA) in the last decades. We aimed to analyze the
      available literature on surgical outcome of EA for the past 80 years. MATERIALS
      AND METHODS:  A PubMed literature search was conducted for the years 1944 to 2017
      using the keywords "esophageal/oesophageal atresia," "outcome," "experience,"
      "management," and "follow-up/follow up." Reports on long-gap EA only, non-English
      articles, case reports, and reviews without original patient data were excluded.
      We focused on mortality and rates of recurrent fistula, leakage, and stricture.
      RESULTS:  Literature search identified 747 articles, 118 manuscripts met the
      inclusion criteria. The first open end-to-end anastomosis and fistula ligation
      was reported in 1941. Thoracoscopic fistula ligation and primary anastomosis was
      performed first in 2000. Reported mortality rate decreased from 100% before 1941
      to 54% in 1950 to 1959, 28% in 1970 to 1979, 16% in 1990 to 1999, and 9%
      nowadays. Rates of recurrent fistula varied over time between 4 and 9%. Leakage
      rate remained stable between 11 and 16%. However, stricture rate increased from
      25 to 38%. CONCLUSION:  Including a full range of articles reflecting the
      heterogeneity of EA, mortality rate significantly decreased during the course of
      80 years. Along with the decrease in mortality, there is a shift to the
      importance of major postoperative complications and long-term morbidity
      regardless of surgical technique.

PMID- 30112749
TI  - Analytical Considerations in Nanoscale Flow Cytometry of Extracellular Vesicles
      to Achieve Data Linearity.
AB  - BACKGROUND:  Platelet microparticles (PMPs) and their abundance in the blood are
      a prognostic biomarker in thrombotic disorders and cancer. Nanoscale flow
      cytometry (nFC) is ideal for high-throughput analysis of PMPs but these clinical
      assays have not been developed previously. OBJECTIVE:  This article demonstrates
      that nFC is a suitable technology to enumerate PMPs present in plasma samples in
      a clinical setting. MATERIALS AND METHODS:  nFC was performed using the Apogee
      A50-Micro instrument. Instrument settings and acquisition parameters were
      developed with the use of fluorescent beads and plasma samples. Sample
      preparation and handling was also optimized. RESULTS:  nFC allows for linear
      detection of particles between approximately 200 and 1,000 nm based on
      calibration beads and was dependent on dilution factor and flow rate. Linearity
      in event analysis as samples became more diluted was lost when events
      approximately 100 nm were gated while linearity was maintained despite dilution
      of sample in events larger than 200 nm in diameter. Higher flow rates lead to an
      under-estimation of events analysed per microlitre of analyte and this was more
      pronounced when plasma samples were not diluted more than 1/20*. CONCLUSION:  nFC
      offers multi-parametric analysis of PMPs when optimal calibration of acquisition
      and sample processing settings is performed. Analysis of plasmas from metastatic
      prostate cancer patients and leukaemia patients revealed that PMP levels were
      larger than 100 nm and were equally abundant in patients that responded to or
      failed androgen deprivation therapy or between patients representing different
      stages of leukaemia.

PMID- 30112750
TI  - Quantification of Platelet Contractile Movements during Thrombus Formation.
AB  - Imaging methods based on time-lapse microscopy are important tools for studying
      the dynamic events that shape thrombus formation upon vascular injury. However,
      there is a lack of methods to translate the vast amount of visual data generated
      in such experiments into quantitative variables describing platelet movements
      that can be subjected to systematic analysis. In this study, we developed
      experimental and computational protocols allowing for a detailed mathematical
      analysis of platelet movements within a developing thrombus. We used a flow
      chamber-based model of thrombosis wherein a collagen strip was used to initiate
      platelet adhesion and activation. Combining the use of a platelet staining
      protocol, designed to enable identification of individual platelets, and image
      processing, we tracked the movements of a large number of individual platelets
      during thrombus formation and consolidation. These data were then processed to
      generate aggregate measures describing the heterogeneous movements of platelets
      in different areas of the thrombus and at different time points. Applying this
      model and its potential, to a comparative analysis on a panel of platelet
      inhibitors, we found that total platelet intra-thrombus movements are only
      slightly reduced by blocking the interactions between glycoproteins IIb/IIIa and
      Ib and their ligands or by inhibiting thromboxane synthesis or P2Y12 signalling.
      In contrast, whereas 30 to 40% of the platelets movements (for the CD42a-labelled
      platelets) and 20% (for the pro-coagulant platelets), within a thrombus, are
      contractile, i.e., towards the centre of the thrombus, this contractile component
      is almost totally abolished in the presence of agents inhibiting these pathways.

PMID- 30112752
TI  - No Escape-A Novel Tool to Quantify Platelet Intra-Thrombus Movements.

PMID- 30112751
TI  - Anticoagulant Effects of Dabigatran in Paediatric Patients Compared with Adults:
      Combined Data from Three Paediatric Clinical Trials.
AB  - BACKGROUND:  Physiological age-related changes in the haemostatic and coagulation
      systems result in differing anticoagulant assay responses to standard
      anticoagulants. Therefore, we investigated the response of anticoagulant assays
      to dabigatran etexilate (DE) in children compared with adults. OBJECTIVE:  This
      article assesses the relationship between plasma dabigatran concentration and
      coagulation assay results across age groups in children and adults. PATIENTS AND
      METHODS:  Data from three clinical trials in which children received DE following
      standard of care for venous thromboembolism were compared with data from adult
      clinical trials. The effects of dabigatran concentration on diluted thrombin time
      (dTT), ecarin clotting time (ECT) and activated partial thromboplastin time
      (aPTT) were analysed graphically and with modelling. RESULTS:  The concentration
      dTT relationships were consistent in children across all ages and adults in the
      graphical analysis. For ECT and aPTT, relationships based on ratios over baseline
      were similar across all ages; absolute clotting times showed that the same
      exposure resulted in longer clotting times in some of the children aged < 1 year
      versus adults. Modelling showed concentration-clotting time relationships for all
      three assays were largely comparable between adults and children, except in those
      aged < 2 months, in whom there was a slight upward shift in ECT and aPTT relative
      to adults. CONCLUSION:  Results suggest that developmental haemostatic changes
      will have little impact on response to DE. However, further paediatric clinical
      trials assessing the relationship between coagulation assay responses and
      clinical outcomes will be needed to confirm this finding.

PMID- 30112753
TI  - Effects of Cutaneous Negative Pressure Application on Perforator Artery Flow in
      Healthy Volunteers: A Preliminary Study.
AB  - INTRODUCTION:  The creation of skin flaps based on small perforator vessels is an
      increasingly popular procedure nowadays; the optimization of their blood supply
      enhances surgical success. This study evaluates the effects on the flowmetries of
      7 days' negative pressure application on the skin surface overlying the muscle
      fascia emergence of periumbilical perforators of the deep inferior epigastric
      artery (DIEA). METHODS:  Ten volunteer participants were enrolled. In each
      subject, one periumbilical perforator of the DIEA was identified on each side of
      the abdomen using an eco-color-Doppler. One of them was used as the control
      group, while the other (the study group) underwent 80 mm Hg negative pressure for
      7 days. The flowmetries of both perforators were measured before and after the
      application of negative pressure wound therapy. RESULTS:  After the application
      of negative pressure, randomly applied on the skin surface over one of the two
      selected periumbilical perforators, an increase in the flowmetries was observed
      in both groups of perforators (2.74 cm/s; p < 0.0001). The relative flowmetry
      increase in the control group was 9.55% (2.735 cm/s), while in the study group it
      was 44.03% (8.748 cm/s). CONCLUSION:  The application of negative pressure system
      on the skin surface over the muscle fascia emergence of the selected
      periumbilical perforators showed an increase in flowmetry. Although this is a
      preliminary study, this simple and economical procedure before surgery could be
      usefully employed to increase the rate of success in microsurgical procedures.

PMID- 30112755
TI  - Modern Neonatal Transport: Sound and Vibration Levels and Their Impact on
      Physiological Stability.
AB  - OBJECTIVE:  To measure sound and vibration in rotary wing air transport (RWAT)
      and ground ambulance transport (GAT), comparing them to current recommendations,
      and correlating them with physiological stability measures in transported
      neonates. STUDY DESIGN:  This is a prospective cohort observational study
      including infants <= 7 days of age transported over an 8-month period. Infants
      with neurologic conditions were excluded. Sound and vibration was continuously
      measured during transport. Transport Risk Index of Physiologic Stability (TRIPS)
      scores were calculated from vital signs as a proxy for physiological stability.
      RESULTS:  In total, 118 newborns were enrolled, of whom 109 were analyzed: 67 in
      RWAT and 42 in GAT. Peak sound levels ranged from 80.4 to 86.4 dBA in RWAT and
      from 70.3 to 71.6 dBA in GAT. Whole-body vibration ranged from 1.68 to 5.09 m/s2
      in RWAT and from 1.82 to 3.96 m/s2 in GAT. Interval TRIPS scores for each infant
      were not significantly different despite excessive sound and vibration.
      CONCLUSION:  Noise levels during neonatal transport exceed published
      recommendations for both RWAT and GAT and are higher in RWAT. Transported infants
      are exposed to vibration levels exceeding acceptable adult standards. Despite
      excessive noise and vibration, levels of physiological stability remained stable
      after transport in both RWAT and GAT groups.

PMID- 30112754
TI  - Unilateral Autologous Breast Reconstruction with Bi-pedicled, Conjoined Deep
      Inferior Epigastric Perforator Flaps.
AB  - BACKGROUND:  The abdomen remains the most popular and reliable donor site for
      autologous breast reconstruction. Some patients, however, lack sufficient tissue
      to recreate an aesthetic breast mound using a single-pedicle, deep inferior
      epigastric perforator (DIEP) flap, particularly when matching a contralateral
      native breast. The amount of abdominal skin and/or soft tissue reliably supplied
      by one vascular pedicle is frequently insufficient to adequately restore the
      breast skin envelope and "footprint." This study summarizes our experience with
      using bipedicled DIEP flaps to improve the aesthetic results of unilateral breast
      reconstruction in such patients. METHODS:  Consecutive patients undergoing
      unilateral breast reconstruction with bi-pedicled, conjoined DIEP flaps over a 4
      year period were retrospectively reviewed. Primary and secondary flap
      microvascular anastomoses were performed to the antegrade internal mammary (IM)
      vessels and to either the retrograde IM vessels or a primary DIEP pedicle side
      branch, respectively. Clinical characteristics and outcomes were recorded.
      RESULTS:  Sixty-three patients underwent immediate (n = 29) or delayed (n = 34)
      reconstruction, with age and body mass index of 54.1 +/- 8.4 years and 26.6 +/-
      4.7, respectively. Mean follow-up was 14.1 months. Twenty-eight (44.4%) patients
      received prereconstruction radiation therapy. All patients had preoperative
      abdominal imaging, including 57 (90.5%) using magnetic resonance angiography.
      There were no flap losses with three operative interventions for flap salvage.
      CONCLUSIONS:  Unilateral breast reconstruction with bipedicled, conjoined DIEP
      flaps is safe and reliable. These procedures can be performed with a complication
      profile similar to single-pedicle DIEP flaps. The additional skin and soft tissue
      available with bi-pedicled flaps allows for greater flexibility in matching the
      shape and projection of a woman's contralateral breast, and in some cases is
      necessary to achieve an aesthetically acceptable reconstruction. With growing
      expectations among breast reconstruction patients, conjoined bi-pedicled flaps
      represent a tool for meeting their reconstructive needs and exceeding the status
      quo for aesthetic outcomes.

PMID- 30112756
TI  - Antenatal Magnesium Sulfate Exposure and Ponderal Index in Preterm Infants.
AB  - OBJECTIVE:  Antenatal magnesium sulfate (MgSO4) is known to affect the central
      nervous system of preterm infants, and there is biologic rationale for influence
      on other phenotypes. This study investigated the effect of MgSO4 exposure on the
      trajectory of ponderal index (PI, kg/m3) from birth to 2 years of age. STUDY
      DESIGN:  A secondary analysis of a U.S. randomized controlled trial investigating
      MgSO4 versus placebo administration among women at high risk for preterm delivery
      was performed. Multivariable logistic regression was used to assess the
      relationship between PI from birth to 2 years of age and exposure to MgSO4 versus
      placebo. RESULTS:  There was a larger decrement in PI from birth to 2 years of
      age in infants exposed to MgSO4 compared with placebo (p = 0.032). There was a
      statistically significant one-way interaction between newborn sex and treatment
      group (p = 0.019). Change in PI in males exhibited a greater decrement in those
      exposed to MgSO4 versus placebo (p = 0.227), whereas female infants exposed to
      MgSO4 had a smaller decrement (p = 0.04). CONCLUSION:  MgSO4 exposure in preterm
      infants is associated with a larger decrease in PI from birth to 2 years of age.
      In addition, the direction of effect of MgSO4 on the change in PI over the first
      2 years of life is different by sex.

PMID- 30112757
TI  - Cervical Cerclage versus Vaginal Progesterone for Management of Short Cervix in
      Low-Risk Women.
AB  - OBJECTIVE:  To evaluate the risk of preterm birth in low-risk women with cervical
      length (CL) <=25 mm on transvaginal ultrasound (TVUS) managed with vaginal
      progesterone (VagP) therapy versus cerclage. STUDY DESIGN:  This is a
      retrospective cohort of women with no prior history of preterm birth or cervical
      insufficiency and CL <= 25 mm on TVUS, managed with either VagP therapy alone or
      cerclage (with or without VagP). The primary outcome was rate of preterm delivery
      < 37 weeks gestational age (GA). Secondary outcomes included delivery at <= 32 or
      <= 28 weeks GA, premature preterm rupture of membranes, pregnancy latency, GA at
      delivery, and composite neonatal outcome. RESULTS:  Women undergoing cerclage
      placement (n = 31) were older and had an earlier GA at the time of diagnosis of
      short cervix compared with women receiving VagP (n = 62). Delivery at < 37 weeks
      occurred in 21/62 (33.9%) in the VagP group and 14/31 (45.2%) in the cerclage
      group (adjusted odds ratio: 1.72, 95% confidence interval: 0.52, 5.66). There
      were no differences in secondary outcomes. CONCLUSION:  Cerclage compared with
      VagP therapy did not decrease risk of preterm birth in women with CL <= 25 mm.
      Further research is needed to determine optimal management in such women given a
      residual 40% risk of preterm birth despite optimal therapy.

PMID- 30112758
TI  - Cultural differences in attitude toward and effects of self-doubt.
AB  - It has been argued that the high achievement of Confucian Asian students is at
      the cost of their psychological well-being, since high self-doubt consistently
      accompanies their high achievement. However, other researchers cautioned that the
      attitude toward self-doubt could be different in Asian versus Western cultures.
      This study examined the debate with a survey of both American and Chinese college
      students that measured level of self-doubt, attitude toward self-doubt, beliefs
      about ability, and psychological well-being outcomes. As hypothesized, Chinese
      students showed a more positive attitude toward self-doubt than American
      students, despite having higher level of self-doubt. Furthermore, self-doubt
      engendered less negative consequences on Chinese students' psychological well
      being, relative to American students. Implications for theories and research on
      cultural differences in the effects of self-constructs are discussed.

PMID- 30112759
TI  - The neural signature of extracting emotional content from rapid visual streams at
      multiple presentation rates: A cross-laboratory study.
AB  - The steady-state visual evoked potential (SSVEP), a neural signature of
      attentional resource allocation, is enhanced for affective compared to neutral
      visual scenes. Recently, it has been demonstrated that modulation of early visual
      cortex associated with viewing of unpleasant scenes presented in a rapid
      succession relies on emotional content extraction from each individual image
      shown in a rapid serial visual presentation (RSVP) at 6 Hz (~167 ms per image).
      Against expectations, the SSVEP was reduced when viewing visual streams of
      unpleasant compared to neutral scenes. Here, we investigated to what extent that
      finding was limited to the 6 Hz rate and whether it generalizes to pleasant
      pictures. We recorded SSVEPs elicited by RSVP of neutral and emotional scenes
      presented at 3, 4, 6.67, and 8.57 Hz rates. We demonstrated that SSVEP amplitudes
      were enhanced for unpleasant compared to neutral images with a presentation rate
      of 3, 4, and 8.57 Hz. By contrast, SSVEP decreased for both pleasant and
      unpleasant relative to neutral RSVP streams shown at 6.67 Hz. Our findings
      suggest that a linear superposition of ERPs evoked by each individual image in an
      RSVP may lead to SSVEP amplitude patterns that increase or decrease the power at
      the driving frequency, which in turn might produce the observed differential
      emotional amplitude modulations. The results provide new methodological
      considerations for investigating temporal dynamics of early visual cortex
      modulation during sustained perception of affective scenes with SSVEP using RSVP
      paradigms.

PMID- 30112760
TI  - Event-related potentials to threat of predictable and unpredictable shock.
AB  - Cognitive affective neuroscience tasks that are straightforward to administer,
      measure key constructs of interest, and can be used in different lab settings and
      with multiple psychophysiological methods can lead to a more complete
      understanding of experimental effects. The no-threat, predictable threat,
      unpredictable threat (NPU-threat) task assesses constructs of interest to both
      clinical and basic affective science literatures, is relatively brief to
      administer, and has been used across labs with a number of different measurements
      (e.g., startle eyeblink, fMRI, corrugator response, subjective ratings). ERPs
      provide another means of assessing neurobiological reactivity during the NPU
      threat task, but to date such measures have been underutilized. That is, no study
      has yet evaluated cue-elicited ERPs in the NPU-threat task. Here, cue-elicited
      ERPs were assessed in 78 participants who completed a version of the NPU-threat
      task previously shown to reliably moderate startle eyeblink amplitudes. Results
      showed larger P2 amplitudes for unpredictable versus predictable trials,
      increased P3s and late positive potentials for threatening versus no-threat
      trials, as well as larger stimulus preceding negativities for threatening versus
      no-threat trials (driven primarily by predictable threat cues). In line with
      prior work, we observed enhanced startle eyeblink for threatening versus no
      threat trials and for unpredictable compared to predictable threat interstimulus
      intervals. In addition, the probe-elicited P3 was suppressed for predictable and
      unpredictable compared to no-threat trials. Therefore, cue-elicited ERPs, which
      can be recorded alongside other measures in the NPU-threat task (e.g., startle),
      may provide useful indices of temporally distinct stages of predictable and
      unpredictable threat processing.

PMID- 30112761
TI  - Impact of CYP1A2 genetic polymorphisms on pharmacokinetics of antipsychotic
      drugs: a systematic review and meta-analysis.
AB  - OBJECTIVE: To determine the impact of CYP1A2 genetic polymorphisms on the
      pharmacokinetics of CYP1A2-metabolized antipsychotic drugs in humans by means of
      systematic review and meta-analysis. METHOD: A systematic search was conducted in
      PubMed and Scopus databases as of June 26, 2018. Studies reporting the
      pharmacokinetic parameters of CYP1A2-metabolized antipsychotic drugs in
      individuals who were genotyped for CYP1A2 genetic polymorphisms were retrieved.
      Pharmacokinetic parameters of individuals who have mutant alleles of a CYP1A2
      genetic polymorphism were compared with the wild-type individuals. Pooled-effect
      estimates, presented as standardized mean difference, were calculated by means of
      the fixed-effect or random-effects model, as appropriate. RESULTS: Ten studies
      involving 872 clozapine users, seven studies involving 712 olanzapine users, and
      two studies involving 141 haloperidol users were included. All but one study
      reported no associations between any CYP1A2 genetic polymorphisms and the
      pharmacokinetics of CYP1A2-metabolized antipsychotic drugs. The pooled-effect
      estimates through meta-analyses of seven studies demonstrated no significant
      associations between the -163C>A or -2467delT polymorphism and clozapine or
      olanzapine concentrations in the blood. CONCLUSIONS: This study suggests that
      CYP1A2 genetic polymorphisms have no significant impact on the pharmacokinetics
      of CYP1A2-metabolized antipsychotic drugs. CYP1A2 genotyping may have no clinical
      implications for personalized dosing of CYP1A2-metabolized antipsychotic drugs.

PMID- 30112763
TI  - Too hard to forget? ERPs to remember, forget, and uninformative cues in the
      encoding phase of item-method directed forgetting.
AB  - In item-method directed forgetting, worse memory performance occurs for to-be
      forgotten (TBF) than for to-be-remembered (TBR) items. However, recently TBF
      items have been found to be recognized more accurately than uninformative (UI)
      items not associated with any specific task. Here, we compare ERPs elicited by
      cues signaling the remember or the forget instruction with those elicited by
      uninformative cues. Participants were presented with a series of complex
      pictures, each followed by a symbolic TBR, TBF, or UI cue. On a yes-no
      recognition test, accuracy was higher for TBR than for both TBF and UI items.
      However, TBF items were recognized more accurately than UI items. ERPs elicited
      by the TBR cue were larger than ERPs elicited by both TBF and UI cues at the
      frontal P2, the late frontal negativity, and the late parietal positivity
      complex. This is consistent with more attention capture, selective rehearsal, and
      long-term memory encoding of TBR. In contrast, both TBF and UI cues induced a
      larger frontal N2 than TBR cues. Critically, TBF elicited a larger late right
      frontal positivity than both UI and TBR cues and a larger late parietal
      positivity than UI cues. Moreover, the late right-frontal positivity was
      correlated with better recognition performance. It may therefore reflect
      processing orientation rather than inhibition per se. Results suggest that, when
      compared to UI cues, both TBR and TBF cues are processed actively. Distinct
      processing is seen at right frontal and centroparietal positive ERPs that may
      mediate better subsequent recognition of TBF than of UI items.

PMID- 30112762
TI  - The positive predictive value of low-density lipoprotein for recurrence-free
      survival in ovarian cancer.
AB  - OBJECTIVE: To evaluate the prognostic impact of preoperative plasma lipid
      profile, glucose, and body mass index in patients with ovarian cancer. METHODS: A
      retrospective study was performed among women with ovarian cancer who underwent
      surgical resection between January 1, 2001, and December 1, 2015, at the First
      Affiliated Hospital of Wenzhou Medical University, China. Data were evaluated
      using Cox regression analyses, Kaplan-Meier survival analysis and landmark
      survival analysis. RESULTS: There were 267 women included in the study.
      Multivariate Cox regression analysis showed that increased levels of low-density
      lipoprotein cholesterol (LDL) were associated with a favorable recurrence-free
      survival (RFS) of ovarian cancer (hazard ratio [HR] 0.18, 95% confidence interval
      [CI] 0.07-0.51). Further Kaplan-Meier survival analysis demonstrated that the
      patients with high levels of LDL (>=3.07 mmol/L) had better RFS compared with the
      patients with low levels of LDL. Moreover, landmark survival analysis indicated
      that a higher LDL level predicted improved 5-year RFS (P=0.026) but not 0.5-year
      RFS (P=0.913) of ovarian cancer. CONCLUSION: Elevated preoperative LDL was
      independently associated with an improved 5-year RFS in women with ovarian
      cancer, thus the utility of LDL could help to predict the recurrence risk for
      patients with ovarian cancer.

PMID- 30112765
TI  - Trametes versicolor glutathione transferase Xi 3, a dual Cys-GST with catalytic
      specificities of both Xi and Omega classes.
AB  - Glutathione transferases (GSTs) from the Xi and Omega classes have a catalytic
      cysteine residue, which gives them reductase activities. Until now, they have
      been assigned distinct substrates. While Xi GSTs specifically reduce glutathionyl
      (hydro)quinones, Omega GSTs are specialized in the reduction of glutathionyl
      acetophenones. Here, we present the biochemical and structural analysis of
      TvGSTX1 and TvGSTX3 isoforms from the wood-degrading fungus Trametes versicolor.
      TvGSTX1 reduces GS-menadione as expected, while TvGSTX3 reduces both Xi and Omega
      substrates. An in-depth structural analysis indicates a broader active site for
      TvGSTX3 due to specific differences in the nature of the residues situated in the
      C-terminal helix alpha9. This feature could explain the catalytic duality of
      TvGSTX3. Based on phylogenetic analysis, we propose that this duality might exist
      in saprophytic fungi and ascomycetes.

PMID- 30112764
TI  - Cancer and dementia: Two sides of the same coin?
AB  - Noncentral nervous system cancer and the brain share an interesting and complex
      relation, with an emerging body of evidence showing that cancer patients are at
      an increased risk of developing cognitive problems. In contrast, population-based
      studies consistently find an inverse link between cancer and dementia, that is
      patients with dementia having a lower risk of subsequently developing cancer, and
      cancer patients being less often diagnosed with dementia. Different biological
      processes such as inversely activated cell proliferation and survival pathways
      have been suggested to have an important role underlying this inverse
      association. However, the effect of methodological biases including surveillance
      or survival bias has not been completely ruled out, calling into question the
      inverse direction of the association between cancer and dementia. In fact,
      emerging evidence now suggests that cancer and dementia might share a positive
      association. This narrative review summarises the current literature on cancer,
      cognitive problems and dementia. Moreover, different strategies will be discussed
      to reduce the impact of potential methodological biases on the association
      between cancer and dementia, trying to reveal the true direction of this link.

PMID- 30112766
TI  - Quality of goal setting in pediatric rehabilitation-A SMART approach.
AB  - BACKGROUND: Setting goals for treatment is often the core of the rehabilitation
      process. The quality of the set goals has however rarely been evaluated. The aims
      of this study were therefore to assess the quality of goals set in clinical
      practice of pediatric rehabilitation using SMART criteria (Specific, Measurable,
      Achievable, Relevant, and Timed) and to assess if the goals were considered
      relevant from both a client perspective and expertise perspective. METHODS: In a
      retrospective multicase study, a total of 161 goals from 42 children with
      disabilities (cerebral palsy, n = 22; Down syndrome, n = 16; and developmental
      disability, n = 4) were assessed. The children were 1.5-5.5 years and had
      previously participated in goal-directed, activity-focused therapy at four
      pediatric rehabilitation centers. Collaborative goal setting had been used to
      define the desired treatment outcome. The quality of the goals was assessed using
      defined SMART criteria. RESULTS: Specific: All goals could be reliably linked to
      International Classification of Functioning, Disability and Health-Children and
      Youth version chapters within the Activity/Participation domain. Measurable: A
      total of 75% of the goals were rated as having a well-defined scaling; in 20%,
      the scaling was less clear, and in 5%, a scaling could not be determined.
      Achievable: A total of 80% of the goals were attained. Relevant: All goals were
      set in collaboration with the family and could therefore be considered relevant
      from a client perspective. Relevancy judged from a professional perspective was
      strengthened by the fact that age, baseline status, and diagnosis had an
      influence on the choice of goals. Timed: All goals were set within a specific
      time frame. CONCLUSIONS: The goals set in clinical practice showed high quality
      with respect to the SMART criteria. The most difficult part was the construction
      of the goal attainment scale. The goals settled in clinical practice were
      considered relevant from both a client perspective and expertise perspective.

PMID- 30112767
TI  - Pallidal and thalamic neural oscillatory patterns in tourette's syndrome.
AB  - OBJECTIVE: Aberrant oscillatory activity has been hypothesized to play a role in
      the pathophysiology of Tourette's syndrome (TS). Deep brain stimulation (DBS) has
      recently been established as an effective treatment for severe TS. Modulation of
      symptom-specific oscillations may underlie the mechanism of action of DBS and
      could be used for adaptive neuromodulation to improve therapeutic efficacy. The
      objective of this study was to demonstrate a pathophysiological association of
      pallidal and thalamic local field potentials (LFPs) with TS. METHODS: Nine
      medication-refractory TS patients were included in the study. Intracerebral LFPs
      were recorded simultaneously from bilateral pallidal and thalamic DBS electrodes.
      Spectral and temporal dynamics of pallidal and thalamic oscillations were
      characterized and correlated with preoperative Yale Global Tic Severity Scale
      (YGTSS) scores. RESULTS: Peaks of activity in the theta (3-12Hz) and beta (13
      35Hz) were present in pallidal and thalamic recordings from all patients (3
      women/6 men; mean age, 29.8 years) and coupled through coherence across targets.
      Presence of prolonged theta bursts in both targets was associated with
      preoperative motor tic severity. Total preoperative YGTSS scores (mean, 38.1)
      were correlated with pallidal and thalamic LFP activity using multivariable
      linear regression (R2 = 0.96; p = 0.02). INTERPRETATION: Our findings suggest
      that pallidothalamic oscillations may be implicated in the pathophysiology of TS.
      Furthermore, our results highlight the utility of multisite and -spectral
      oscillatory features in severely affected patients for future identification and
      clinical use of oscillatory physiomarkers for adaptive stimulation in TS. Ann
      Neurol 2018;84:505-514.

PMID- 30112768
TI  - Characterization of bound water in skin hydrators prepared with and without a
      3D3P interpenetrating polymer network.
AB  - BACKGROUND: Hyaluronic acid (HA) has been considered the gold standard ingredient
      for improving skin hydration and combating age-related effects, however it is an
      inefficient polymer with inconsistent results partially due to its poor skin
      penetration, surface deposition, and rapid degradation. Herein we report the
      synthesis and in vitro characterization of a newly developed, topical super
      humectant with the goal of attracting and binding water molecules more
      efficiently than traditional, cosmetic-grade forms of HA. METHODS: A modified
      interpenetrating polymer network (IPN) was developed using three polymers into a
      three-dimensional formation (3D3P) for entrapping HA and water. This 3D3P-IPN
      functions as a super-humectant, attracting and binding water molecules more
      efficiently than the traditional cosmetic-grade forms of HA. We compare 3D3P-IPN
      serum samples to a traditional commercial benchmark product of similar
      ingredients using microscopic analysis, rheology, Karl Fischer (KF) titration,
      differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and
      dynamic vapor sorption (DVS) techniques. RESULTS: The 3D3P-IPN samples appeared
      to bind water tighter than the benchmark sample as evidenced by maximum endpoints
      of endotherms occurring at significantly higher temperatures. The DVS results
      further confirm this speculation as the 3D3P-IPN samples lost approximately 10%
      less water up to 35% RH than the benchmark. The 3D3P-IPN samples also absorbed
      more water as the humidity level increased,demonstrating superior humectant
      properties. KF titration indicated that all three samples had similar water
      concentrations; however, TGA results demonstrated that the benchmark (a viscous,
      humectant-rich hydrating masque) did not have much bound water. CONCLUSION:
      Through the synthesis of a 3D3P-IPN using simplified methods, we were able to
      increase the water-binding and HA-delivery capabilities of a thin serum. This
      3D3P-IPN serum has potential to deliver more hydration to the skin's surface
      compared to traditional HA formulations.

PMID- 30112769
TI  - A smart algorithm for the prevention and risk management of QTc prolongation
      based on the optimized RISQ-PATH model.
AB  - AIMS: QTc prolongation is a complex problem linked with multiple risk factors.
      The RISQ-PATH score was previously developed to identify high-risk patients for
      QTc prolongation. The aim of this study was to optimize and validate this risk
      score in a large patient cohort, and to propose an algorithm to generate smart QT
      signals in the electronic medical record. METHODS: A retrospective study was
      performed in the Nexus hospital network (n = 17) in Belgium. All
      electrocardiograms performed in 2015 in both ambulatory and hospitalized patients
      were collected together with risk factors for QTc prolongation (training
      database). Multiple logistic regression was performed to obtain the optimal
      prediction (RISQ-PATH) model. The model was tested in a validation database
      (electrocardiograms between January and April 2016). RESULTS: In total, 60 208
      patients (52.8% males, mean age 63 +/- 18 years) were included; 3543 patients
      (5.9%) had a QTc >= 450(?)/470(?) ms and 453 (0.8%) a QTc >= 500 ms. The
      optimized RISQ-PATH model has an area under the ROC-curve of 0.772 [95% CI 0.763
      0.780] to predict QTc >= 450(?)/470(?)ms. A predicted probability of >=0.035 was
      set as cutoff for a high risk of QTc prolongation. This cutoff resulted in a
      sensitivity of 87.4% [95% CI 86.2-88.5] and a specificity of 46.2% [95% CI 45.8
      46.6]. These results could be confirmed for QTc >= 500 ms and in the validation
      database (n = 28 400). CONCLUSIONS: The RISQ-PATH model, with a cutoff
      probability of 0.035, predicted a prolonged QTc interval >= 450/470 ms or >=500
      ms with a sensitivity of +/-87% and a specificity of +/-45%. This RISQ-PATH model
      can be used in clinical decision support systems to create smart QT alerts.

PMID- 30112770
TI  - MUC4 expression in meningiomas: under-recognized immunophenotype particularly in
      meningothelial and angiomatous subtypes.
AB  - AIMS: MUC4 is a transmembrane glycoprotein that plays a role in cell growth
      signalling and is expressed in various epithelial tissues. Gene expression
      profiling and immunohistochemical analyses revealed that MUC4 is also constantly
      and specifically expressed in low-grade fibromyxoid sarcomas and sclerosing
      epithelioid fibrosarcomas among the mesenchymal tumours, and immunohistochemical
      detection of MUC4 is extremely useful for their diagnoses. In our routine
      pathological practice, we noticed that meningiomas are also often positive for
      MUC4, which has not yet been reported previously, despite the extensive scrutiny
      of its expression in soft tissue tumours. METHODS AND RESULTS: We examined
      immunohistochemically the expression of MUC4, progesterone receptor (PgR) and
      somatostatin receptor 2A (SSTR2A) in 140 meningiomas of various histological
      subtypes and 123 other mesenchymal tumours, including intracranial or sinonasal
      tumours and peripheral nerve sheath tumours. MUC4 was expressed in 130
      meningiomas (92.9%). MUC4 expression was constant and almost diffuse in
      meningothelial and angiomatous subtypes, whereas it was limited in 5% or fewer
      tumour cells or absent in 26 of 28 fibrous meningiomas. All other mesenchymal
      tumours examined were negative for MUC4. PgR and SSTR2A were expressed in 94
      (67.1%) and 134 (95.7%) meningiomas, respectively. Five of six SSTR2A-negative
      meningiomas focally expressed MUC4. CONCLUSIONS: MUC4 is expressed variably but
      almost consistently in meningiomas, particularly in meningothelial or angiomatous
      subtypes. Its immunohistochemical detection is useful to distinguish meningiomas
      from other intracranial or head and neck mesenchymal tumours, particularly those
      with epithelioid features. Our study could expand a variety of MUC4-positive
      mesenchymal tumours.

PMID- 30112771
TI  - Early postpartum discharge: maternal depression, breastfeeding habits and
      different follow-up strategies.
AB  - BACKGROUND: In most maternity wards in Norway, early discharge (<48 hour) is the
      norm. To monitor newborns' and women's health during the first week after
      delivery, most maternity wards offer early check-ups, where families return to
      the hospital (standard care). However, a few municipalities offer home visits by
      midwives (domiciliary care) to ensure seamless services for the family. AIM: The
      primary aim of this study was to explore whether different follow-up strategies
      were differently associated with maternal depression and breastfeeding habits, 6
      weeks and 6 months postpartum. The secondary aim was to investigate whether
      families at risk of postpartum depression were included in the home visiting
      programme in the municipality that offered both follow-up strategies. METHOD:
      This study draws on data from the 'Little in Norway' (LIN) study, which followed
      families from pregnancy until the child was 18 months. This study used data from
      two different well-baby clinics in two municipalities, where one offered standard
      care (n = 95) and the other domiciliary (n = 64) and standard care (n = 17). The
      Edinburg Postnatal Depression Scale (EPDS) was used to measure maternal
      depression. Breastfeeding habits were measured using a self-report questionnaire.
      The Life Stress subscale of the Parenting Stress Index (PSI) was used to identify
      women at risk of postpartum depression. RESULTS: There were no differences in
      maternal depressive symptoms or breastfeeding habits at neither 6 weeks nor 6
      months postpartum between women who received standard or domiciliary care in the
      two municipalities. Within the municipality that offered both follow-up
      strategies, a higher number of women scoring high on prenatal life stress were
      included in domiciliary - compared to standard care. CONCLUSION: Differential
      follow-up strategies in the first week after birth did not impact on maternal
      depression or breastfeeding habits. However, domiciliary care seems to be
      regarded as supportive and nonstigmatising for women at risk of postpartum
      depression.

PMID- 30112772
TI  - Mirabegron or tolterodine for the treatment of overactive bladder in Japan: Which
      drug is more cost-effective as the first-line treatment?
AB  - OBJECTIVES: To assess the cost-effectiveness of mirabegron 50 mg relative to
      tolterodine extended release 4 mg for the treatment of overactive bladder if used
      as the first-line treatment in Japan. METHODS: A Markov model was developed to
      simulate the cost-effectiveness of the mirabegron first-line treatment (and
      tolterodine second-line) versus tolterodine first-line treatment (and mirabegron
      second-line) taken for 5 years from the randomized European-Australian study
      (SCORPIO trial) and single technology appraisal assessment report by the National
      Institute for Health and Care Excellence. The incremental cost-effectiveness
      ratio was calculated with utility value by quality-adjusted life year with cost
      using the medical fee and the drug price tariff in 2016. For the study of
      transition of treatment status, our analytical model was established. The
      transition probabilities of severity states were calculated based on the
      probabilities for the mean numbers of incontinence episodes/day and micturition
      episodes/day in mirabegron-treated and tolterodine-treated patients in the single
      technology appraisal assessment report. RESULTS: The 5-year expected effect per
      patient was 3.860 quality-adjusted life years for first-line mirabegron and 3.839
      quality-adjusted life years for first-line tolterodine. The 5-year expected cost
      per patient was Y526 191 for first-line mirabegron, and Y472 390 for first-line
      tolterodine. The incremental cost-effectiveness ratio was Y2 565 927/quality
      adjusted life year. This value was below the willingness-to-pay threshold of Y5
      million/quality-adjusted life year. In more severe states, the incremental cost
      effectiveness ratio exceeded Y5 million. CONCLUSIONS: First-line mirabegron
      appears to be more cost-effective than first-line tolterodine. In patients with
      severe symptoms, first-line mirabegron is not economically preferable.

PMID- 30112773
TI  - Being in control and striving for normalisation: A Norwegian pilot study on
      parents' perceptions of hospital-at-home.
AB  - In recent decades, there has been a shift from hospitalisation to home care
      throughout the Western world, even for children. Hospital-at-home for children is
      in a developmental phase and represents a new service model in Norway. The aim of
      this pilot study conducted in a Norwegian healthcare setting was to explore how
      parents with a sick child experienced early hospital discharge and further care
      at home. The qualitative data are drawn from nine interviews with parents with a
      child admitted to hospital-at-home. Transcripts of interviews were analysed using
      a method of qualitative content analysis. In the analysis, Antonovsky's
      salutogenic perspective on how people cope in demanding life situations was
      applied. The results show that the parents experienced hospital-at-home as
      providing a calmer, more predictable family life compared to hospitalisation.
      They argued that good information and training in medical procedures prior to
      hospital discharge made hospital-at-home easier to master. The participants
      pointed out the importance of the professionals' competence and their ability to
      interact with the child and the parent. The certitude that they could return to
      the hospital at any time made them feel safe and in control. The parents
      associated hospital-at-home with a kind of normalisation of their family life.
      They had a prominent need for normalisation, and this was probably a motivation
      for agreeing to the hospital-at-home arrangement. The findings indicate that
      hospital-at-home for children is a good solution if the parents are well prepared
      and feel in control. In addition, certain structural conditions must be in place
      before this type of health care is established; there must be a certain volume of
      patients and the distance to the hospital must be clearly limited. Norwegian
      policymakers should initiate more pilot testing of hospital-at-home for children.
      Users and clinicians should be involved in establishing and evaluating these
      services.

PMID- 30112774
TI  - Autoimmunity and immune system dysregulation in schizophrenia: IgGs from sera of
      patients hydrolyze myelin basic protein.
AB  - Several different theories of schizophrenia (SCZ) were discussed; the causes of
      this disease are not yet clear. Using ELISA, it was shown that titers of
      autoantibodies against myelin basic protein (MBP) in SCZ patients are ~1.8-fold
      higher than in healthy individuals but 5.0-fold lower than in patients with
      multiple sclerosis. Several rigid criteria were checked to show that the MBP
      hydrolyzing activity is an intrinsic property of SCZ IgGs. Approximately 82%
      electrophoretically homogeneous SCZ IgGs purified using several affinity sorbents
      including Sepharose with immobilized MBP hydrolyze specifically only MBP but not
      many other tested proteins. The average relative activity of IgGs from patients
      with negative symptoms was 2.5-fold higher than that of patients with positive
      symptoms of SCZ, and it increases with the duration of this pathology. It was
      shown that abzymes are the earliest statistically significant markers of many
      autoimmune pathologies. Our findings surmise that the immune systems of
      individual SCZ patients can generate a variety of anti-MBP abzymes with different
      catalytic properties, which can attack MBP of the myelin-proteolipid shell of
      axons. Therefore, autoimmune processes together with other mechanisms can play an
      important role in SCZ pathogenesis. MBP-hydrolyzing antibodies were previously
      detected in the blood of 80% to 90% of patients with systemic lupus erythematosus
      (SLE) and multiple sclerosis (MS). In addition, some similar neuropsychiatric
      indicators of disease common to SLE, MS, and SCZ were described in the
      literature. Thus, the destruction of the myelin sheath and the production of MBP
      hydrolyzing antibodies can be a common phenomenon for some different diseases.

PMID- 30112775
TI  - Monocytes are involved in the balance between regulatory T cells and Th17 cells
      in severe drug eruptions.
AB  - BACKGROUND: Drug-induced hypersensitivity syndrome/drug reaction with
      eosinophilia and systemic symptoms (DiHS/DRESS) is a distinct phenotype of severe
      drug eruptions characterized by sequential reactivations of herpesviruses.
      Although a progressive loss of suppressive function in regulatory T cells (Tregs)
      occurred during the course of DiHS/DRESS, but not in Stevens-Johnson
      syndrome/toxic epidermal necrolysis (SJS/TEN), no previous studies investigated
      the mechanism. Given the recent finding that Treg development could be
      differentially regulated by CD16+ patrolling monocytes (pMOs) and CD14+ classical
      monocytes (cMOs), we can hypothesize that a differential fine-tuned interaction
      between Tregs and monocytes is the driving force behind the possible shift from
      Tregs to Th17 cells over a prolonged period of time in DiHS/DRESS. OBJECTIVE: To
      investigate whether the shift from Treg to Th17 could specifically occur during
      the course of DiHS/DRESS and to elucidate which subsets of monocytes could be
      involved in the shift. METHODS: We performed a prospective longitudinal study on
      the frequencies of Tregs, Th17 cells and monocyte subsets after onset of
      DiHS/DRESS and SJS/TEN, and long after their clinical resolutions. We next
      examined whether pMOs and cMOs could have a strong impact on the Th17/Treg
      differentiation and which cytokines could be crucial for the interaction between
      Th17/Tregs and MO subsets, by in vitro cocultures. RESULTS: Selective depletion
      of pMOs occurring at the acute stage of DiHS/DRESS was associated with the
      relative increase in the frequencies of cMOs producing IL-10 and it did drive
      Treg expansions. After clinical resolution, pMOs producing IL-6 were
      alternatively recruited and contributed to the eventual shift from a Treg to Th17
      responses. CONCLUSIONS AND CLINICAL RELEVANCE: The gradual shift from Treg to
      Th17 cell development observed during the clinical course of DiHS/DRESS is
      mediated by the predominance of cMOs at the acute stage and alternatively
      recruited pMOs at the resolution stage, respectively.

PMID- 30112776
TI  - Simplified approach to uncertainty of measurement in the clinical virology
      laboratory.
AB  - Medical laboratories are required to ensure the quality of their diagnostic
      results. Quality assurance procedures include quality assessments (internal and
      external), quality controls (negative, positive, or internal controls), equipment
      monitoring, and audits. Quality control data may be used to evaluate the
      uncertainty of measurement. All clinical virology laboratories require a standard
      operating procedure detailing their consideration of uncertainty of measurement,
      as this parameter may impact on the overall quality of diagnostic results as well
      as the clinical interpretation thereof. This review aims to provide a simplified
      approach to the concept of uncertainty of measurement, specific for clinical
      virology laboratories.

PMID- 30112777
TI  - FtsW activity and lipid II synthesis are required for recruitment of MurJ to
      midcell during cell division in Escherichia coli.
AB  - Peptidoglycan (PG) is the unique cell shape-determining component of the
      bacterial envelope, and is a key target for antibiotics. PG synthesis requires
      the transmembrane movement of the precursor lipid II, and MurJ has been shown to
      provide this activity in Escherichia coli. However, how MurJ functions in vivo
      has not been reported. Here we show that MurJ localizes both in the lateral
      membrane and at midcell, and is recruited to midcell simultaneously with late
      localizing divisome proteins and proteins MraY and MurG. MurJ septal localization
      is dependent on the presence of a complete and active divisome, lipid II
      synthesis and PBP3/FtsW activities. Inactivation of MurJ, either directly by
      mutation or through binding with MTSES, did not affect the midcell localization
      of MurJ. Our study visualizes MurJ localization in vivo and reveals a possible
      mechanism of MurJ recruitment during cell division.

PMID- 30112778
TI  - The Use of Calcium Carbide as Acetylene Source in a Three-Component Coupling with
      omega-Chlorinated Ketones and Primary Amines.
AB  - Calcium carbide was used in a CuI -catalysed three-component coupling with omega
      chlorinated ketones and primary amines to generate terminal 2-alkynyl-N
      heterocycles. The formation of an imine and the subsequent intramolecular
      substitution results in an active electrophilic iminium species, which can be
      alkynylated by in situ formed copper acetylide. A number of aliphatic primary
      (functionalised) amines and aliphatic or aromatic alkynes together with different
      alkyl- or aryl-substituted gamma- or delta-chloroketones could be used. Simple
      acid-base workup instead of column chromatography can be applied to obtain the
      resulting 2-alkynylpyrrolidines and 2-alkynylpiperidines.

PMID- 30112779
TI  - Risk of hospital admission for liver injury in users of NSAIDs and nonoverdose
      paracetamol: Preliminary results from the EPIHAM study.
AB  - PURPOSE: The SALT study found similar per-user risks of acute liver failure (ALF)
      leading to transplantation (ALFT) between NSAIDs and a threefold higher risk in
      nonoverdose paracetamol (NOP) users. The objective of EPIHAM was to identify the
      risks of hospital admission for acute liver injury (ALI) associated with NSAIDs
      and NOP. METHODS: Case-population study in the 1/97 sample of the French
      population claims database. Acute liver injury was identified from hospital
      discharge summaries, from 2009 to 2013. Exposure for cases was dispensing of
      NSAID or NOP resulting in exposure within 30 days before admission. Population
      exposure was the number of patients using the drugs over the study timeframe and
      total number of DDD dispensed. RESULTS: Of 63 cases of ALI, 13 had been exposed
      to NSAIDs and 24 to NOP. Events per million DDD (95% CI) ranged from 0.46 (0.09
      1.34) (ketoprofen) to 1.43 (0.04-7.97) (diclofenac combinations), 0.43 (0.23
      0.73) all NSAIDs combined, 0.58 (0.37-0.86) for NOP. There was no association
      with average duration of treatment. Per patient risk ranged from 19.5 (5.31-49.9)
      (ibuprofen) per million users to 37.2 (19.8-63.6) all NSAIDs combined, 58.0 (37.2
      86.3) for NOP. There was a linear relationship between average treatment duration
      and per-user risk (R2  = 0.51, P < .05 for NSAIDs, R2  = 0.97, P < .01 for NOP).
      CONCLUSIONS: Risk of hospital admission for ALI with NSAIDs and NOP was similar
      and indicative of a dose and duration-related effect (pharmacological) effect.
      Acute liver injury rates were not predictive of ALFT risk.

PMID- 30112780
TI  - Species-specific phenological trends in shallow Pampean lakes' (Argentina)
      zooplankton driven by contemporary climate change in the Southern Hemisphere.
AB  - The relationship between the timing of recurrent biological events and seasonal
      climatic patterns (i.e., phenology) is a crucial ecological process. Changes in
      phenology are increasingly linked to global climate change. However, current
      evidence of phenological responses to recent climate change is subjected to
      substantial regional and seasonal biases. Most available evidence on climate
      driven phenological changes comes from Northern Hemisphere (NH) ecosystems and
      typically involves increases in spring and summer temperatures, which translate
      into earlier onsets of spring population developments. In the Argentine Pampa
      region, warming has occurred at a much slower pace than in the NH, and trends are
      mostly restricted to increases in the minimum temperatures. We used zooplankton
      abundance data from Lake Chascomus (recorded every two weeks from 2005 to 2015)
      to evaluate potential changes in phenology. We adopted a sequential screening
      approach to identify taxa displaying phenological trends and evaluated whether
      such trends could be associated to observe long-term changes in water
      temperature. Two zooplankton species displayed significant later shifts in
      phenology metrics (end date of Brachionus havanaensis seasonal distribution: 31
      day/decade, onset and end dates of Keratella americana seasonal distribution: 59
      day/decade and 82 day/decade, respectively). The timing of the observed shift in
      B. havanaensis phenology was coincident with a warming trend in the May lake
      water temperature (4.7 degrees C per decade). Analysis of abundance versus
      temperature patterns from six additional shallow Pampean lakes, and evaluation of
      previous experimental results, provided further evidence that the lake water
      warming trend in May was responsible for the delayed decline of B. havanaensis
      populations in autumn. This study is the first report of freshwater zooplankton
      phenology changes in the Southern Hemisphere (SH).

PMID- 30112782
TI  - High Diagnostic Uncertainty and Inaccuracy in Adult Emergency Department Patients
      With Dyspnea: A National Database Analysis.

PMID- 30112781
TI  - An amphipathic cyclic tetrapeptide scaffold containing halogenated beta2,2 -amino
      acids with activity against multiresistant bacteria.
AB  - The present study describes the synthesis and biological studies of a small
      series of head-to-tail cyclic tetrapeptides of the general structure c(Lys
      beta2,2 -Xaa-Lys) containing one lipophilic beta2,2 -amino acid and Lys, Gly,
      Ala, or Phe as the Xaa residue in the sequence. The peptides were investigated
      for antimicrobial activity against gram-positive and gram-negative reference
      strains and 30 multiresistant clinical isolates including strains with extended
      spectrum beta-lactamase-carbapenemase (ESBL-CARBA) production. Toxicity was
      determined against human red blood cells. The most potent peptides showed high
      activity against the gram-positive clinical isolates with minimum inhibitory
      concentrations of 4-8 MUg/mL and low haemolytic activity. The combination of high
      antimicrobial activity and low toxicity shows that these cyclic tetrapeptides
      containing lipophilic beta2,2 -amino acids form a valuable scaffold for designing
      novel antimicrobial agents.

PMID- 30112784
TI  - Measured Steps: Evidence-based Anti-Trafficking Efforts in the Emergency
      Department.

PMID- 30112783
TI  - Retrospective review of Acquired Haemophilia A from the largest Canadian
      Haemophilia treatment centre.

PMID- 30112787
TI  - Bethanechol: Is it still being prescribed for bladder dysfunction in women?
AB  - PURPOSE: Few medical treatment options exist for detrusor underactivity or
      urinary retention in women. Bethanechol, a cholinergic agonist, may improve
      detrusor contractility in these conditions; however, its clinical efficacy is
      limited. We sought to examine the patterns of Bethanechol use by physicians in an
      ambulatory care setting using a national database to determine if it is still
      prescribed for patients with bladder dysfunction. MATERIALS AND METHODS: The
      National Ambulatory Medical Care Survey (NAMCS) database was queried for a sample
      of patient visits to office-based physicians from 2003-2013. Visits were included
      for women aged 18 years or older with diagnosed lower urinary tract symptoms
      (LUTS), neurogenic bladder, or urinary retention based on ICD-9-CM codes. Visits
      in which Bethanechol was prescribed were analysed with descriptive statistics.
      Sampling weights were adjusted for nonresponders to yield an unbiased national
      estimate of ambulatory care visits. RESULTS: Out of a weighted sample of 17 321
      630 included patient visits, 132 281 (0.8%) visits included a prescription for
      Bethanechol. Patients prescribed Bethanechol had a mean age of 62.3 +/- 2.1 and
      were predominantly Caucasian (67%) followed by African American (18%). The
      primary diagnosis associated with Bethanechol was atony of bladder (35%), urinary
      retention (20%), neurogenic bladder (18%), urinary incontinence (16%), and
      incomplete bladder emptying (10%). Visits were primarily for chronic conditions
      (63%). It was typically prescribed as a continued medication (79%) most often by
      urologists (92%) followed by internal medicine clinicians (8%). CONCLUSIONS:
      Bethanechol continues to be prescribed in elderly women primarily for detrusor
      atony, urinary retention, or incomplete bladder emptying.

PMID- 30112785
TI  - Psychiatry's contribution to the public stereotype of schizophrenia: Historical
      considerations.
AB  - The public stereotype of schizophrenia is characterized by craziness, a split
      personality, unpredictable and dangerous behaviour, and by the idea of a chronic
      brain disease. It is responsible for delays in help-seeking, encourages social
      distance and discrimination, and furthers self-stigmatization. This paper
      discusses the circumstances of the origins of the idea of a chronic brain disease
      (Emil Kraepelin, 1856-1926), of the split personality concept derived from the
      term "schizophrenia" (Eugen Bleuler, 1857-1939), and the craziness idea reflected
      in the "first rank symptoms", which are all hallucinations and delusions (Kurt
      Schneider, 1887-1967). It shows how Emil Kraepelin's scientific search for
      homogenous groups of patients with a common aetiology, symptom pattern, and
      prognosis materialized in the definition of "dementia praecox" as a progressing
      brain disease; how Eugen Bleuler's life and professional circumstances
      facilitated an "empathic" approach to his patients and prompted him to put in the
      foreground incoherence of cognitive and affective functioning, and not the course
      of the disease; finally, how Kurt Schneider in his didactic attempt to teach
      general practitioners how to reliably diagnose schizophrenia, neglected what Emil
      Kraepelin and Eugen Bleuler had emphasized decades earlier and devised his own
      criteria, consisting exclusively of hallucinations and delusions. In a strange
      conglomerate, the modern operational diagnostic criteria reflect all three
      approaches, by claiming to be Neo-Kraepelinean in terms of defining a categorical
      disease entity with a suggestion of chronicity, by keeping Bleuler's ambiguous
      term schizophrenia, and by relying heavily on Kurt Schneider's hallucinations and
      delusions. While interrater reliability may have improved with operational
      diagnostic criteria, the definition of schizophrenia is still arbitrary and has
      no empirical validity-but induces stigma.

PMID- 30112788
TI  - Effect of family education program on cognitive impairment, anxiety, and
      depression in persons who have had a stroke: A randomized, controlled study.
AB  - People who have had a stroke face high risks of cognitive impairment, anxiety,
      and depression. Health education for family members contributes to better
      outcomes in various diseases, but the effects of health education on family
      members of people who have had a stroke are unclear. The aim of the present study
      was to evaluate the effects of the family member education program (FMEP) on
      cognitive impairment, anxiety, and depression in persons who have had a stroke.
      In total, 144 persons who experienced a stroke were randomly allocated to the
      FMEP group or control group (1:1 ratio). In the FMEP group, the FMEP and
      conventional treatment were provided, while in control group only conventional
      treatment was provided. The increase in the Montreal Cognitive Assessment (MOCA)
      score from baseline to 12 months (M12 - baseline) in the FMEP group was higher
      compared with the control group, and the FMEP led to a decreased cognitive
      impairment rate (MOCA score <=26) after 12 months compared to the control group.
      Changes in the Hospital Anxiety and Depression Scale anxiety and depression score
      (M12 - baseline) decreased in the FMEP group compared with the control group.
      Fewer participants with depression and a lower depression grade were observed in
      the FMEP group compared with the control group. The FMEP could reduce cognitive
      impairment, anxiety, and depression in persons who have had a stroke.

PMID- 30112789
TI  - On the recent developments of insulator-based dielectrophoresis: A review.
AB  - Insulator-based dielectrophoresis (iDEP), also known as electrodeless DEP, has
      become a well-known dielectrophoretic technique, no longer viewed as a new
      methodology. Significant advances on iDEP have been reported during the last 15
      years. This review article aims to summarize some of the most important findings
      on iDEP organized by the type of dielectrophoretic mode: streaming and trapping
      iDEP. The former is primarily used for particle sorting, while the latter has
      great capability for particle enrichment. The characteristics of a wide array of
      devices are discussed for each type of dielectrophoretic mode in order to present
      an overview of the distinct designs and applications developed with iDEP. A short
      section on Joule heating effects and electrothermal flow is also included to
      highlight some of the challenges in the utilization of iDEP systems. The
      significant progress on iDEP illustrates its potential for a large number of
      applications, ranging from bioanalysis to clinical and biomedical assessments.
      The present article discusses the work on iDEP by numerous research groups around
      the world, with the aim of proving the reader with an overview of the state-of
      the-art in iDEP microfluidic systems.

PMID- 30112786
TI  - Effect of insulin treatment on circulating insulin-like growth factor I and IGF
      binding proteins in cats with diabetes mellitus.
AB  - BACKGROUND: Insulin-like growth factor-I (IGF-I) is used to screen for acromegaly
      in diabetic cats. In humans, most circulating IGF-I forms ternary complexes (TC)
      with IGF-binding protein (IGFBP-3) and an acid-labile subunit. Compared to
      humans, the amount of TC in cats is more variable. Insulin-like growth factor-I
      concentrations are reported to increase during insulin treatment, more rapidly in
      cats achieving remission. OBJECTIVES: To investigate (i) factors associated with
      circulating IGF-I concentrations, including IGFBP-profiles (ii) effect of insulin
      treatment on IGF-I concentrations and (iii) IGF-I as prognostic marker of
      diabetes mellitus remission. ANIMALS: Thirty-one privately owned diabetic cats of
      which 24 were followed 1 year, and 13 healthy cats. METHODS: Prospective study.
      Serum insulin, IGF-I, glucose, and fructosamine concentrations were measured. IGF
      binding forms were determined by chromatography in 14 diabetic and 13 healthy
      cats; and IGF-I, IGF-II, IGFBP-3, and IGFBP-5 by mass spectrometry in 3 cats
      achieving remission. RESULTS: Insulin-like growth factor-I median (interquartile
      range) before start of insulin treatment was 300 (160-556) ng/mL. Insulin-like
      growth factor-I was positively associated with TC (P < .0001) and endogenous
      insulin (P = .005) and negatively associated with fructosamine (P < .0001).
      Median IGF-I was higher 2-4 weeks after start of insulin treatment compared with
      baseline (300 versus 670 ng/mL, P = .0001) and predicted future remission (P =
      .046). In cats that went into remission, the amount of TC and IGFBP-3 increased,
      suggesting increase in IGF-I is dependent on TC formation. CONCLUSIONS: Insulin
      treatment should be accounted for when interpreting IGF-I in diabetic cats.
      Insulin-like growth factor-I 2-4 weeks after initiation of insulin treatment
      shows promise as prognostic marker for remission in diabetic cats.

PMID- 30112790
TI  - High performance liquid chromatography associated with resonance Rayleigh
      scattering for synchronous determination of three antihistamines and mechanism
      study.
AB  - A highly sensitive and selective method of high performance liquid chromatography
      (HPLC) combined with resonance Rayleigh scattering (RRS) spectra was developed
      for the detection of three antihistamine drugs, including pyrilamine (PY),
      carbinoxamine (CAR) and tripelennamine (TRI). The three antihistamines were
      separated by a C18 column. The mobile phase contained 25% acetonitrile (ACN) and
      75% phosphate buffered solution (pH 3.2) with the flow rate of 0.4 ml min-1 . In
      medium of Britton-Robinson (BR) buffer solution (pH 4.6), the PY, CAR and TRI
      separated by HPLC and then reacted with Erythrosine B (EryB), forming 1:1 ion
      association complexes, which led to significant signal enhancement of RRS
      spectra. The RRS spectra was detected at the wavelength lambdaex =lambdaem = 370
      nm. The calibration curves of PY, CAR and TRI were linear in the range from 0.02
      to 25 MUg ml-1 , and the detection limit [signal-to-noise ratio (S/N) = 3] were
      3.38, 4.48 and 5.50 ng ml-1 , respectively. In addition, under the optimum
      experiment condition, the reaction mechanism and the reasons for RRS enhancement
      were investigated in this work. The developed method was applied to the
      simultaneous detection of three antihistamines in water samples with satisfying
      results.

PMID- 30112791
TI  - Enantioselective Total Synthesis of (+)-Plumisclerin A.
AB  - The first and enantioselective total synthesis of (+)-plumisclerin A, a novel
      unique complex cytotoxic marine diterpenoid, has been accomplished. Around the
      central cyclopentane anchorage, a sequential ring-formation protocol was adopted
      to generate the characteristic tricycle[4.3.1.01,5 ]decane and trans-fused
      dihyrdopyran moiety. Scalable enantioselective LaIII -catalyzed Michael reaction,
      palladium(0)-catalyzed carbonylation and SmI2 -mediated radical conjugate
      addition were successfully applied in the synthesis, affording multiple grams of
      the complex and rigid B/C/D-ring system having six continuous stereogenic centers
      and two all-carbon quaternary centers. The trans-fused dihyrdopyran moiety with
      an exo side-chain was furnished in final stage through sequential redox
      transformations from a lactone precursor, which overcome the largish steric
      strain of the dense multiring system. The reported total synthesis also confirms
      the absolute chemistries of natural (+)-plumisclerin A.

PMID- 30112792
TI  - Efficacy and safety of MYL-1501D versus insulin glargine in patients with type 2
      diabetes after 24 weeks: Results of the phase III INSTRIDE 2 study.
AB  - AIMS: To assess the non-inferiority of MYL-1501D, a proposed biosimilar or follow
      on biological agent to marketed insulin glargine, to reference insulin glargine
      (Lantus(r); Sanofi-Aventis US LLC, Bridgewater, New Jersey) based on change in
      glycated hemoglobin (HbA1c). MATERIALS AND METHODS: INSTRIDE 2 was a multicentre,
      open-label, randomized, parallel-group, phase III non-inferiority study comparing
      the efficacy and safety of MYL-1501D with those of reference insulin glargine in
      insulin-naive and insulin-non-naive patients with type 2 diabetes mellitus
      receiving oral antidiabetic drugs (OADs). The primary efficacy endpoint was
      change in HbA1c from baseline to week 24. Secondary endpoints included metabolic
      readouts (eg, changes in fasting plasma glucose, insulin dosage, self-monitored
      blood glucose), immunogenicity and adverse events, including hypoglycaemia and
      nocturnal hypoglycaemic events. RESULTS: In all, 560 patients were randomized to
      MYL-1501D or insulin glargine in combination with OADs for 24 weeks. The mean
      change in HbA1c from baseline to week 24 was -0.60% (95% CI -0.78, -0.41) and -
      0.66% (95% CI -0.84, -0.48) for MYL-1501D and reference insulin glargine,
      respectively. MYL-1501D was well tolerated and had a safety profile similar to
      that of reference insulin glargine. CONCLUSIONS: Demonstration of non-inferiority
      between MYL-1501D and reference insulin glargine for reduction of HbA1c during 24
      weeks of treatment was achieved. The two treatment groups were similar in terms
      of secondary endpoints, including hypoglycaemia and nocturnal hypoglycaemia,
      local and systemic reactions, other safety variables, and immunogenicity.

PMID- 30112793
TI  - Operando X-Ray Absorption Spectroscopy Shows Iron Oxidation Is Concurrent with
      Oxygen Evolution in Cobalt-Iron (Oxy)hydroxide Electrocatalysts.
AB  - Iron cations are essential for the high activity of nickel and cobalt-based
      (oxy)hydroxides for the oxygen evolution reaction, but the role of iron in the
      catalytic mechanism remains under active investigation. Operando X-ray absorption
      spectroscopy and density functional theory calculations are used to demonstrate
      partial Fe oxidation and a shortening of the Fe-O bond length during oxygen
      evolution on Co(Fe)Ox Hy . Cobalt oxidation during oxygen evolution is only
      observed in the absence of iron. These results demonstrate a different mechanism
      for water oxidation in the presence and absence of iron and support the
      hypothesis that oxidized iron species are involved in water-oxidation catalysis
      on Co(Fe)Ox Hy .

PMID- 30112794
TI  - Photochromic Benzo[b]phosphole Alkynylgold(I) Complexes with Mechanochromic
      Property to Serve as Multistimuli-Responsive Materials.
AB  - A series of novel benzo[b]phosphole alkynylgold(I) complexes has been
      demonstrated to display photochromic and mechanochromic properties upon applying
      the respective stimuli of light and mechanical force. Promising multistimuli
      responsive properties of this series of gold(I) complexes have been successfully
      achieved through judicious molecular design, which involves incorporation of the
      photochromic dithienylethene-containing benzo[b]phosphole into the triphenylamine
      containing arylethynyl ligand that is susceptible to mechanical force-induced
      color changes via gold(I) complexation. With excellent thermal irreversibility
      and robust fatigue resistance of this series of gold(I) complexes, multicolor
      states controlled by the photochromism and mechanochromism have been realized.
      Repeatable photochromic and mechanochromic cycles without apparent loss of
      reactivity have also been observed under ambient conditions. The present work
      provides important insight and an alternative strategy for the molecular design
      of multistimuli-responsive materials, paving the way for further development of
      the underexplored photoresponsive gold(I) complexes and the multistate
      photocontrolled system.

PMID- 30112795
TI  - Interaction studies of lead(II) ion with cyclic beta-(1->3),(1->6) glucans
      extracted from Bradyrhizobium japonicum based on 'chelation enhanced
      fluorescence' (CHEF) effect.
AB  - Cyclic beta-(1->3),(1->6) glucans (CBGs) isolated from Bradyrhizobium japonicum
      bacteria are the periplasmic oligosaccharides having cyclic structures. This
      paper presents the isolation of CBGs from the bacteria cultured using optimized
      medium that improved yields to 350-450 mg per gram of cellular dry weight along
      with analytical interaction with lead(II) ions in the range 33.0-2.0 ppm with CBG
      as a binding ligand, using constant wavelength synchronous fluorescence
      spectroscopy. The binding ability of CBGs towards lead(II) is clearly evident
      from the scanning electron microscopy (SEM) images. The theoretical calculations
      using HEX 8.0 gave an insight about the interaction between CBG and lead(II) to
      be in the ratio of 3:1. The method displayed the sensitivity and selectivity
      towards lead(II) ions up to 2.0 ppm. This observed property of CBGs can
      potentially hold an application in bioremediation of the soil contaminated with
      lead.

PMID- 30112796
TI  - Nanofiber-Directed Anisotropic Self-Assembly of CdSe-CdS Quantum Rods for
      Linearly Polarized Light Emission Evidenced by Quantum Rod Orientation
      Microscopy.
AB  - Hybrid soft materials composed of CdSe-CdS nanorods or "quantum rods" (QRs) and
      the fluorescent 2,3-didecyloxyanthracene (DDOA) low molecular weight
      organogelator are obtained through self-assembly. Spectroscopy, microscopy, and
      rheology studies show that the QRs and DDOA coassemble, thereby stabilizing the
      organogels. Depending on the QR load and excitation wavelength, single nanofibers
      (NFs) of the hybrid gel display either sharp polarized red luminescence (under
      green excitation), or dual perpendicularly polarized blue and red emissions
      (under UV excitation). Transmission electron microscopy, microspectroscopy, and
      quantum rod orientation microscopy (QROM) reveal that QRs align along the
      organogel NFs with order parameters reaching 76% and 87%. This paves the way for
      obtaining surfaces of QR/NF assemblies yielding sharp red linearly polarized
      emission. In addition, this work demonstrates that QRs can be used more generally
      to probe nanostructured soft materials, even nonemissive ones. QROM allows to
      establish maps of the orientation of single QRs dispersed onto or within a gel
      network by measuring the polarization of the emission of the individual QRs. As
      occurs within this work in which QRs and NFs interact, the orientation of each QR
      reveals information on the underlying nanostructure (such as surface striation,
      bundle formation, and helicity).

PMID- 30112798
TI  - Painful hemorrhagic bullae on the dorsal hands.

PMID- 30112799
TI  - A Literal Elytral Rainbow: Tunable Structural Colors Using Single Diamond
      Biophotonic Crystals in Pachyrrhynchus congestus Weevils.
AB  - The brilliant colors of many insects arise from the interference of incident
      light with complex nanostructured biomaterials that are present in their cuticle.
      Here, the rainbow-colored spots on the elytra of a snout weevil, Pachyrrhynchus
      congestus pavonius (Coleoptera: Curculionidae), are investigated using
      synchrotron small-angle X-ray scattering, scanning electron microscopy,
      microspectrophotometry, and photonic bandgap modeling. It is shown that the
      iridescent scales present in the rainbow-hued spots are due to a 3D photonic
      crystal network of chitin in air with a single diamond (Fd-3m) symmetry. In many
      insects, different orientations of photonic crystal domains are used to create
      various hues. In this weevil, however, both the chitin volume fractions as well
      as the lattice parameters of the biologically self-assembled single diamond
      nanostructure are varied to achieve the remarkable tuning of the structural
      colors across the visible light spectrum on a scale-by-scale basis. Uncovering
      the precise mechanism of color tuning employed by this weevil has important
      implications for further structural and developmental research on biophotonic
      nanostructures and may provide fresh impetus for bioinspired and biomimetic
      multifunctional applications, as synthesis of photonic crystals at visible length
      scales is currently challenging.

PMID- 30112800
TI  - Multisite phosphorylation provides a reliable mechanism for making decisions in
      noisy environments.
AB  - The ability to make decisions at the cellular level is absolutely critical for
      the survival of organisms. Eukaryotic cells are constantly making binary
      decisions in response to internal and environmental signals. Among the most
      notable transducers of information are protein kinases. The regulation of these
      signaling proteins often relies on the activity of other protein kinases located
      upstream in the signaling cascade. However, these signaling systems are by their
      own nature an important source of molecular noise. Herein, we have assessed the
      role of multisite phosphorylation in detecting signals in the face of molecular
      noise. To address this issue, we have conceptually envisioned the biochemical
      transduction machinery as a classifier model that can lead to four possible
      outputs: true positives and negatives, and false positives and negatives. In this
      probabilistic framework, we show that multisite phosphorylation represents a
      mechanism to filter noise during the decision-making process. We present results
      showing that nonessential phosphorylation sites contribute to increase the rate
      of true positives while, at the same time, they can lessen the rate of false
      positives. This simultaneous increase in sensitivity and specificity, makes
      multisite phosphorylation a valuable and easily implemented mechanism to reliably
      transduce information in noisy contexts.

PMID- 30112797
TI  - Evaluation of automatic contour propagation in T2-weighted 4DMRI for normal
      tissue motion assessment using internal organ-at-risk volume (IRV).
AB  - PURPOSE: The purpose of this study was to evaluate the quality of automatically
      propagated contours of organs at risk (OARs) based on respiratory-correlated
      navigator-triggered four-dimensional magnetic resonance imaging (RC-4DMRI) for
      calculation of internal organ-at-risk volume (IRV) to account for intra
      fractional OAR motion. METHODS AND MATERIALS: T2-weighted RC-4DMRI images were of
      10 volunteers acquired and reconstructed using an internal navigator-echo
      surrogate and concurrent external bellows under an IRB-approved protocol. Four
      major OARs (lungs, heart, liver, and stomach) were delineated in the 10-phase
      4DMRI. Two manual-contour sets were delineated by two clinical personnel and two
      automatic-contour sets were propagated using free-form deformable image
      registration. The OAR volume variation within the 10-phase cycle was assessed and
      the IRV was calculated as the union of all OAR contours. The OAR contour
      similarity between the navigator-triggered and bellows-rebinned 4DMRI was
      compared. A total of 2400 contours were compared to the most probable ground
      truth with a 95% confidence level (S95) in similarity, sensitivity, and
      specificity using the simultaneous truth and performance level estimation
      (STAPLE) algorithm. RESULTS: Visual inspection of automatically propagated
      contours finds that approximately 5-10% require manual correction. The
      similarity, sensitivity, and specificity between manual and automatic contours
      are indistinguishable (P > 0.05). The Jaccard similarity indexes are 0.92 +/-
      0.02 (lungs), 0.89 +/- 0.03 (heart), 0.92 +/- 0.02 (liver), and 0.83 +/- 0.04
      (stomach). Volume variations within the breathing cycle are small for the heart
      (2.6 +/- 1.5%), liver (1.2 +/- 0.6%), and stomach (2.6 +/- 0.8%), whereas the IRV
      is much larger than the OAR volume by: 20.3 +/- 8.6% (heart), 24.0 +/- 8.6%
      (liver), and 47.6 +/- 20.2% (stomach). The Jaccard index is higher in navigator
      triggered than bellows-rebinned 4DMRI by 4% (P < 0.05), due to the higher image
      quality of navigator-based 4DMRI. CONCLUSION: Automatic and manual OAR contours
      from Navigator-triggered 4DMRI are not statistically distinguishable. The
      navigator-triggered 4DMRI image provides higher contour quality than bellows
      rebinned 4DMRI. The IRVs are 20-50% larger than OAR volumes and should be
      considered in dose estimation.

PMID- 30112801
TI  - Saturated two-photon excitation fluorescence microscopy for the visualization of
      cerebral neural networks at millimeters deep depth.
AB  - Optical imaging is a key modality for observing biological specimen with higher
      spatial resolution. However, scattering and absorption of light in tissues are
      inherent barriers in maximizing imaging depth in biological tissues. To achieve
      this goal, use of light at near-infrared spectrum can improve the present
      situation. Here, the capability of saturated two-photon saturated excitation (TP
      SAX) fluorescence microscopy to image at depths of >2.0 mm, with submicron
      resolution in transparent mouse brain imaging, is demonstrated. At such depths
      with scattering-enlarged point spread function (PSF), we find that TP-SAX is
      capable to provide spatial resolution improvement compared to its corresponding
      TPFM, which is on the other hand already providing a much improved resolution
      compared with single-photon confocal fluorescence microscopy. With the capability
      to further improve spatial resolution at such deep depth with scattering-enlarged
      PSF, TP-SAX can be used for exquisite visualization of delicate cerebral neural
      structure in the scattering regime with a submicron spatial resolution inside
      intact mouse brain.

PMID- 30112802
TI  - Single step genomic evaluation for female fertility in Nordic Red dairy cattle.
AB  - Joint Nordic (Denmark, Finland, Sweden) genetic evaluation of female fertility is
      currently based on the multiple trait multilactation animal model (BLUP). Here,
      single step genomic model (ssGBLUP) was applied for the Nordic Red dairy cattle
      fertility evaluation. The 11 traits comprised of nonreturn rate and days from
      first to last insemination in heifers and first three parities, and days from
      calving to first insemination in the first three parities. Traits had low
      heritabilities (0.015-0.04), but moderately high genetic correlations between the
      parities (0.60-0.88). Phenotypic data included 4,226,715 animals with records and
      pedigree 5,445,392 animals. Unknown parents were assigned into 332 phantom parent
      groups (PPG). In mixed model equations animals were associated with PPG effects
      through the pedigree or both the pedigree and genomic information. Genotype
      information of 46,914 SNPs was available for 33,969 animals in the pedigree. When
      PPG used pedigree information only, BLUP converged after 2,420 iterations whereas
      the ssGBLUP evaluation needed over ten thousand iterations. When the PPG effects
      were solved accounting both the pedigree and the genomic information, the ssGBLUP
      model converged after 2,406 iterations. Also, with the latter model breeding
      values by ssGBLUP and BLUP became more consistent and genetic trends followed
      each other well. Models were validated using forward prediction of the young
      bulls. Reliabilities and variance inflation of predicted genomic breeding values
      (values for parent averages in brackets) for the 11 traits ranged 0.22-0.31 (0.10
      0.27) and 0.81-0.95 (0.83-1.06), respectively. The ssGBLUP model gave always
      higher validation reliabilities than BLUP, but largest increases were for the cow
      fertility traits.

PMID- 30112803
TI  - Painful blisters and erosions after gardening.

PMID- 30112804
TI  - Effect of a statistical outlier in potency bioassays.
AB  - The USP<1032> guidelines recommend the screening of bioassay data for outliers
      prior to performing a relative potency (RP) analysis. The guidelines, however, do
      not offer advice on the size or type of outlier that should be removed prior to
      model fitting and calculation of RP. Computer simulation was used to investigate
      the consequences of ignoring the USP<1032> guidance to remove outliers. For
      biotherapeutics and vaccines, outliers in potency data may result in the false
      acceptance/rejection of a bad/good lot of drug product. Biological activity,
      measured through a potency bioassay, is considered a critical quality attribute
      in manufacturing. If the concentration-response potency curve of a test sample is
      deemed to be similar in shape to that of the reference standard, the curves are
      said to exhibit constant RP, an essential criterion for the interpretation of a
      RP. One or more outliers in the concentration-response data, however, may result
      in a failure to declare similarity or may yield a biased RP estimate.
      Concentration-response curves for test and reference were computer generated with
      constant RP from four-parameter logistic curves. Single outlier, multiple
      outlier, and whole-curve outlier scenarios were explored for their effects on the
      similarity testing and on the RP estimation. Though the simulations point to
      situations for which outlier removal is unnecessary, the results generally
      support the USP<1032> recommendation and illustrate the impact on the RP
      calculation when application of outlier removal procedures are discounted.

PMID- 30112805
TI  - Bluish grey pigmentation.

PMID- 30112806
TI  - Subgroup-specific dose finding in phase I clinical trials based on time to
      toxicity allowing adaptive subgroup combination.
AB  - A Bayesian design is presented that does precision dose finding based on time to
      toxicity in a phase I clinical trial with two or more patient subgroups. The
      design, called Sub-TITE, makes sequentially adaptive subgroup-specific decisions
      while possibly combining subgroups that have similar estimated dose-toxicity
      curves. Decisions are based on posterior quantities computed under a logistic
      regression model for the probability of toxicity within a fixed follow-up period,
      as a function of dose and subgroup. Similarly to the time-to-event continual
      reassessment method (TITE-CRM, Cheung and Chappell), the Sub-TITE design
      downweights each patient's likelihood contribution using a function of follow-up
      time. Spike-and-slab priors are assumed for subgroup parameters, with latent
      subgroup combination variables included in the logistic model to allow different
      subgroups to be combined for dose finding if they are homogeneous. This framework
      can be used in trials where clinicians have identified patient subgroups but are
      not certain whether they will have different dose-toxicity curves. A simulation
      study shows that, when the dose-toxicity curves differ between all subgroups, Sub
      TITE has superior performance compared with applying the TITE-CRM while ignoring
      subgroups and has slightly better performance than applying the TITE-CRM
      separately within subgroups or using the two-group maximum likelihood approach of
      Salter et al that borrows strength among the two groups. When two or more
      subgroups are truly homogeneous but differ from other subgroups, the Sub-TITE
      design is substantially superior to either ignoring subgroups, running separate
      trials within all subgroups, or the maximum likelihood approach of Salter et al.
      Practical guidelines and computer software are provided to facilitate
      application.

PMID- 30112807
TI  - A noninvasive imaging and measurement using optical coherence tomography
      angiography for the assessment of gingiva: An in vivo study.
AB  - Gingiva is the soft tissue that surrounds and protects the teeth. Healthy gingiva
      provides an effective barrier to periodontal insults to deeper tissue, thus is an
      important indicator to a patient's periodontal health. Current methods in
      assessing gingival tissue health, including visual observation and physical
      examination with probing on the gingiva, are qualitative and subjective. They may
      become cumbersome when more complex cases are involved, such as variations in
      gingival biotypes where feature and thickness of the gingiva are considered. A
      noninvasive imaging technique providing depth-resolved structural and vascular
      information is necessary for an improved assessment of gingival tissue and more
      accurate diagnosis of periodontal status. We propose a three-dimensional (3D)
      imaging technique, optical coherence tomography (OCT), to perform in situ imaging
      on human gingiva. Ten volunteers (five male, five female, age 25-35) were
      recruited; and the labial gingival tissues of upper incisors were scanned using
      the combined use of state-of-the-art swept-source OCT and OCT angiography (OCTA).
      Information was collected describing the 3D tissue microstructure and capillary
      vasculature of the gingiva within a penetration depth of up to 2 mm. Results
      indicate significant structural and vascular differences between the two extreme
      gingival biotypes (ie, thick and thin gingiva), and demonstrate special features
      of vascular arrangement and characteristics in gingival inflammation. Within the
      limit of this study, the OCT/OCTA technique is feasible in quantifying different
      attributes of gingival biotypes and the severity of gingival inflammation.

PMID- 30112808
TI  - Methanogenic community during the anaerobic digestion of different substrates and
      organic loading rates.
AB  - Three anaerobic reactors using pig manure (PM), maize straw (MS), and a mixture
      of the two as substrates were compared for archaeal community structure and
      diversity, and for methanogens response to increased organic loading rate (OLR,
      expressed in the mass of volatile solid (VS)). Methanogenic archaeal richness
      during codigestion of pig manure with maize straw (ACE: 2412) was greater than
      that during the others (ACE: 1225, 1467) at an OLR of 4 g L-1  day-1 ,
      accompanied by high specific methane yield. Euryarchaeota and Crenarchaeota
      predominated during overall digestion of different substrates; with relative
      abundances of 63.5%-99.0% and 1.0%-36.3%, respectively. Methanosarcina was the
      predominant genus that accounted for 33.7%-79.8% of the archaeal community. The
      diversity in the PM digester decreased with increase in OLR, but increased in the
      MS digester. The diversity was stable during the codigestion with increased OLR.
      The relative abundances of hydrogenotrophic methanogens increased by 2.6 and 2.1
      folds; the methanogenic community shifted from acetoclastic to hydrogenotrophic
      methanogens during digestion of MS, and of the mixture of MS and PM. Canonical
      correspondence analysis revealed a strong relationship between reactor parameters
      and methanogenic community.

PMID- 30112809
TI  - Paediatric intensive care and neonatal intensive care airway management in the
      United Kingdom: the PIC-NIC survey.
AB  - In 2011, the Fourth National Audit Project (NAP4) reported high rates of airway
      complications in adult intensive care units (ICUs), including death or brain
      injury, and recommended preparation for airway difficulty, immediately available
      difficult airway equipment and routine use of waveform capnography monitoring.
      More than 80% of UK adult intensive care units have subsequently changed
      practice. Undetected oesophageal intubation has recently been listed as a 'Never
      Event' in UK practice, with capnography mandated. We investigated whether the
      NAP4 recommendations have been embedded into paediatric and neonatal intensive
      care practice by conducting a telephone survey of senior medical or nursing staff
      in UK paediatric intensive care units (PICUs) and neonatal intensive care units
      (NICUs). Response rates were 100% for paediatric intensive care units and 90% for
      neonatal intensive care units. A difficult airway policy existed in 67% of
      paediatric intensive care units and in 40% of neonatal intensive care units; a
      pre-intubation checklist was used in 70% of paediatric intensive care units and
      in 42% of neonatal intensive care units; a difficult intubation trolley was
      present in 96% of paediatric intensive care units and in 50% of neonatal
      intensive care units; a videolaryngoscope was available in 55% of paediatric
      intensive care units and in 29% of neonatal intensive care units; capnography was
      'available' in 100% of paediatric intensive care units and in 46% of neonatal
      intensive care units, and 'always available' in 100% of paediatric intensive care
      units and in 18% of neonatal intensive care units. Death or serious harm
      occurring secondary to complications of airway management in the last 5 years was
      reported in 19% of paediatric intensive care units and in 26% of neonatal
      intensive care units. We conclude that major gaps in optimal airway management
      provision exist in UK paediatric intensive care units and especially in UK
      neonatal intensive care units. Wider implementation of waveform capnography is
      necessary to ensure compliance with the new 'Never Event' and has the potential
      to improve airway management.

PMID- 30112810
TI  - Targeting of AKT/ERK/CTNNB1 by DAW22 as a potential therapeutic compound for
      malignant peripheral nerve sheath tumor.
AB  - Malignant peripheral nerve sheath tumors (MPNSTs) are an aggressive form of soft
      tissue neoplasm with extremely poor prognosis and no effective medical options
      currently available. MPNSTs can occur either sporadically or in association with
      the neurofibromatosis type 1 (NF1) syndrome. Importantly, activation of
      RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, and WNT/CTNNB1 signaling pathways has been
      reported in both NF1-related and late-stage sporadic MPNSTs. In this study, we
      found that DAW22, a natural sesquiterpene coumarin compound isolated from Ferula
      ferulaeoides (Steud.) Korov., could inhibit cell proliferation and colony
      formation in five established human MPNST cancer cell lines. Further molecular
      mechanism exploration indicated that DAW22 could target the main components in
      the MPNST tumorigenic pathways: namely suppress phosphorylation of AKT and ERK,
      and reduce levels of non-phospho (active) CTNNB1. Using the xenograft mouse model
      transplanted with human MPNST cancer cell line, daily treatment with DAW22 for 25
      days was effective in reducing tumor growth. These results support DAW22 as an
      alternative therapeutic compound for MPNST treatment by affecting multiple
      signaling transduction pathways in its disease progression.

PMID- 30112811
TI  - Pain assessment and management in haemophilia: A survey among Italian patients
      and specialist physicians.
AB  - INTRODUCTION: Persons with haemophilia (PWH) experience recurrent joint bleeding
      which leads from early synovitis to irreversible joint damage. Pain strongly
      affects patients' quality of life, as PWH suffer from acute pain associated with
      haemarthroses and chronic pain due to arthritic and degenerative complications.
      AIM: To investigate pain issues among PWH and their treaters in Italy. METHODS:
      Persons with haemophilia and specialist physicians responded to a survey focused
      on pain characteristics, assessment, and management by phone call and online,
      respectively. RESULTS: One hundred and nineteen patients (76% severe haemophilia,
      61% >=18 years) and 44 physicians were involved. Pain was reported by 61% of PWH;
      among those who did not experience pain, 70% were children on prophylaxis.
      Patients described pain as chronic (71%), acute (69%) or postoperative (8%), and
      rated it as severe in 65% of cases. Clinicians reported lower percentages of
      patients with pain (46%), classified as chronic (58%), acute (33%) or
      postoperative (21%), half using specific scales. Pain was systematically
      investigated by treaters according to 36% of patients. Paracetamol was largely
      the most prescribed first-line pain therapy (89%), as well the most employed
      analgesic by PWH (51%), who also used non-steroidal anti-inflammatory drugs
      (24%), cyclo-oxygenase-2 inhibitors (21%) or opioids (26%). To manage pain, 61%
      of clinicians stated to collaborate with other specialists. Physiotherapy was
      often suggested but less frequently used by PWH. CONCLUSIONS: Pain is under
      recognized and unsatisfactorily addressed by haemophilia treatment centre (HTC)
      clinicians, with discrepant management compared to PWH responses. Education in
      systematic pain assessment and multidisciplinary treatment and development of
      management guidelines are highly needed.

PMID- 30112812
TI  - Functional connectivity changes in the entorhinal cortex of taxi drivers.
AB  - INTRODUCTION: As a major interface between the hippocampus and the neocortex, the
      entorhinal cortex (EC) is widely known to play a pivotal role in spatial memory
      and navigation. Previous studies have suggested that the EC can be divided into
      the anterior-lateral (alEC) and the posterior-medial subregions (pmEC), with the
      former receiving object-related information from the perirhinal cortex and the
      latter receiving scene-related information from the parahippocampal cortex.
      However, the functional connectivity maps of the EC subregions in the context of
      extensive navigation experience remain elusive. In this study, we analyzed the
      functional connectivity of the EC in subjects with long-term navigation
      experience and aimed to find the navigation-related change in the functional
      properties of the human EC. METHODS: We investigated the resting-state functional
      connectivity changes in the EC subregions by comparing the EC functional
      connectivity maps of 20 taxi drivers with those of 20 nondriver controls.
      Furthermore, we examined whether the functional connectivity changes of the EC
      were related to the number of taxi driving years. RESULTS: Significantly reduced
      functional connectivity was found in the taxi drivers between the left pmEC and
      the right anterior cingulate cortex (ACC), right angular gyrus, and bilateral
      precuneus as well as some temporal regions, and between the right pmEC and the
      left inferior temporal gyrus. Notably, the strength of the functional
      connectivity between the left pmEC and the left precuneus, as well as the right
      ACC, was negatively correlated with the years of taxi driving. CONCLUSION: This
      is the first study to explore the impact of long-term navigation experience on
      the connectivity patterns of the EC, the results of which may shed new light on
      the potential influence of extensive navigational training on the functional
      organization of the EC in healthy human brains.

PMID- 30112815
TI  - Acculturation gaps in diaspora immigrant adolescent-mother dyads: The case for a
      domain-, group- and context-specific view on family adaptation.
AB  - Intergenerational value mismatch in immigrant families, also termed acculturation
      gap, is well documented. However, in increasingly diverse societies, the
      generalizability of this phenomenon across immigrant groups, across dimensions
      and domains of acculturation, and across different receiving societies is
      questionable. This comparative study investigated mother-adolescent acculturation
      gaps of two diaspora immigrant samples, who had lived in the former Soviet Union
      for generations, across two receiving societies (Germany vs. Israel), across two
      dimensions (ethnic vs. host) in two domains of adaptation (behavioural: language
      vs. cognitive: identity). In addition, we investigated whether these
      acculturation gaps are detrimental or beneficial for mother-adolescent
      communication. Participants comprised 342 diaspora immigrants divided into 80
      German repatriate mother-adolescent dyads in Germany (adolescents' mean age: 16.9
      years, 48.8% female) and 91 Russian Jewish mother-adolescent dyads in Israel
      (adolescents' mean age: 15.8 years, 51.6% female) who were interviewed in person
      at their homes. Results indicated diaspora-specific effects in ethnic identity,
      with adolescents identifying more closely with their ethnic culture than their
      mothers. Our study highlights that acculturation gaps can undermine parent-child
      communication across both contexts, although we also found some context-specific
      effects.

PMID- 30112816
TI  - Stakeholder participation on the path to universal health coverage: the use of
      evidence-informed deliberative processes.

PMID- 30112814
TI  - Time-frequency approaches to investigating changes in feedback processing during
      childhood and adolescence.
AB  - Processing feedback from the environment is an essential function during
      development to adapt behavior in advantageous ways. One measure of feedback
      processing, the feedback negativity (FN), is an ERP observed following the
      presentation of feedback. Findings detailing developmental changes in the FN have
      been mixed, possibly due to limitations in traditional ERP measurement methods.
      Recent work shows that both theta and delta frequency activity contribute to the
      FN; utilizing time-frequency methods to measure change in power and phase in
      these frequency bands may provide more accurate representation of feedback
      processing development in childhood and adolescence. We employ time-frequency
      power and intertrial phase synchrony measures, in addition to conventional time
      domain ERP methods, to examine the development of feedback processing in the
      theta (4-7 Hz) and delta (.1-3 Hz) bands throughout adolescence. A sample of 54
      female participants (8-17 years old) completed a gambling task while EEG was
      recorded. As expected, time-domain ERP amplitudes showed no association with age.
      In contrast, significant effects were observed for the time-frequency measures,
      with theta power decreasing with age and delta power increasing with age. For
      intertrial phase synchrony, delta synchrony increased with age, while age-related
      changes in theta synchrony differed for gains and losses. Collectively, these
      findings highlight the importance of considering time-frequency dynamics when
      exploring how the processing of feedback develops through late childhood and
      adolescence. In particular, the role of delta band activity and theta synchrony
      appear central to understanding age-related changes in the neural response to
      feedback.

PMID- 30112813
TI  - Altered physiological brain variation in drug-resistant epilepsy.
AB  - INTRODUCTION: Functional magnetic resonance imaging (fMRI) combined with
      simultaneous electroencephalography (EEG-fMRI) has become a major tool in mapping
      epilepsy sources. In the absence of detectable epileptiform activity, the resting
      state fMRI may still detect changes in the blood oxygen level-dependent signal,
      suggesting intrinsic alterations in the underlying brain physiology. METHODS: In
      this study, we used coefficient of variation (CV) of critically sampled 10 Hz
      ultra-fast fMRI (magnetoencephalography, MREG) signal to compare physiological
      variance between healthy controls (n = 10) and patients (n = 10) with drug
      resistant epilepsy (DRE). RESULTS: We showed highly significant voxel-level (p <
      0.01, TFCE-corrected) increase in the physiological variance in DRE patients. At
      individual level, the elevations range over three standard deviations (sigma)
      above the control mean (MU) CVMREG values solely in DRE patients, enabling
      patient-specific mapping of elevated physiological variance. The most apparent
      differences in group-level analysis are found on white matter, brainstem, and
      cerebellum. Respiratory (0.12-0.4 Hz) and very-low-frequency (VLF = 0.009-0.1 Hz)
      signal variances were most affected. CONCLUSIONS: The CVMREG increase was not
      explained by head motion or physiological cardiorespiratory activity, that is, it
      seems to be linked to intrinsic physiological pulsations. We suggest that
      intrinsic brain pulsations play a role in DRE and that critically sampled fMRI
      may provide a powerful tool for their identification.

PMID- 30112817
TI  - A hybrid volumetric dose verification method for single-isocenter multiple-target
      cranial SRS.
AB  - A commercial semi-empirical volumetric dose verification system (PerFraction
      [PF], Sun Nuclear Corp.) extracts multi-leaf collimator positions from the
      electronic portal imaging device movies collected during a pre-treatment run,
      while the rest of the delivered control point information is harvested from the
      accelerator log files. This combination is used to reconstruct dose on a patient
      CT dataset with a fast superposition/convolution algorithm. The method was
      validated for single-isocenter multi-target SRS VMAT treatments against absolute
      radiochromic film measurements in a cylindrical phantom. The targets ranged in
      size from 0.8 to 3.6 cm and in number from 3 to 10 per plan. A total of 17 films
      rotated at different angles around the cylinder axis were analyzed. Each of 27
      total targets was intercepted by at least one film, and 2-4 different films were
      analyzed per plan. Film dose was always scaled to the ion chamber measurement in
      a high-dose, low-gradient area deliberately created at the isocenter. The planar
      dose agreement between PF and film using 3%(Global dose-difference
      normalization)/1 mm gamma analysis was on average 99.2 +/- 1.1%. The point dose
      difference in the low-gradient area in the middle of every target was below 3%,
      while PF-reconstructed and film dose centroids for individual targets showed
      submillimeter agreement when measured on a well aligned accelerator.
      Volumetrically, all voxels in all plans agreed between PF and the primary
      treatment planning system at the 3%/1 mm level. With proper understanding of its
      advantages and shortcomings, the tool can be applied to patient-specific QA in
      routine radiosurgical clinical practice.

PMID- 30112818
TI  - ATP reduction by MgtC and Mg2+ homeostasis by MgtA and MgtB enables Salmonella to
      accumulate RpoS upon low cytoplasmic Mg2+ stress.
AB  - RpoS is one of several alternative sigma factors known to alter gene expression
      profiles by RpoS-associated RNA polymerase in response to a variety of stresses.
      The enteric bacteria Salmonella enterica and Escherichia coli accumulate RpoS
      under low Mg2+ concentrations via a common mechanism in which the PhoP regulator
      activates expression of antiadaptor proteins that, by sequestering the adaptor
      RssB, prevent RpoS degradation by the protease ClpXP. Here, we demonstrate that
      this genetic program alone does not fully support RpoS accumulation when
      cytoplasmic Mg2+ concentration drops to levels that impair protein synthesis.
      Under these circumstances, only S. enterica continues RpoS accumulation in a
      manner dependent on other PhoP-activated programs (i.e. ATP reduction by the MgtC
      protein and Mg2+ import by the MgtA and MgtB transporters) that maintain
      translation homeostasis. Moreover, we provide evidence that the mgtC gene, which
      is present in S. enterica but not in E. coli, is responsible for the differences
      in RpoS accumulation between these two bacterial species. Our results suggest
      that bacteria possess a mechanism to control RpoS accumulation responding to
      cytoplasmic Mg2+ levels, the difference of which causes distinct RpoS
      accumulation in closely related bacterial species.

PMID- 30112820
TI  - Donor-Specific Antibodies in Pediatric Intestinal and Multivisceral
      Transplantation: The Role of Liver and Human Leukocyte Antigen Mismatching.
AB  - Rejection is one of the most important drawbacks for graft and patient survival
      in intestinal and multivisceral transplantation. However, there is no consensus
      on the diagnostic criteria for humoral rejection, and the literature about the
      role of donor-specific antibodies (DSA) on allograft outcome and the risk factors
      that contribute to their development is scant with contradictory results. The
      present study analyzes the role of DSA exclusively in a pediatric cohort of 43
      transplants. Among our patients, 11.6% showed preformed DSA, but they did not
      correlate with more rejection or less allograft survival. Having previous
      transplants was the main sensitization factor with an odds ratio (OR) = 44.85 (P
      = 0.001). In total, 16.3% of recipients developed de novo donor-specific
      antibodies (dnDSA), mostly directed against human leukocyte antigen (HLA) class
      II, polyspecific and complement fixing. Additionally, the presence of dnDSA had a
      deleterious effect on graft rejection (hazard ratio [HR] = 11.00; P = 0.01) and
      survival (HR = 66.52; P < 0.001) in an observational period of 5 years after
      transplantation. The inclusion of the liver emerged as the main protective factor
      against dnDSA development with an OR = 0.07 (P = 0.007). The analysis of HLA
      compatibility at the serological and epitope level with the computational tools
      HLAMatchmaker and PIRCHE revealed no association between HLA mismatching and
      dnDSA. In conclusion, this study performed in pediatric recipients shows the
      deleterious effect of dnDSA on intestinal transplantation supported by the
      complement-fixing activity observed. Additionally, the liver inclusion in the
      allografts showed to be a protective factor against dnDSA generation.

PMID- 30112819
TI  - Long-term views on chronic kidney disease research priorities among stakeholders
      engaged in a priority-setting partnership: A qualitative study.
AB  - BACKGROUND: Patients and stakeholders are increasingly engaging in health
      research to help address evidence-practice gaps and improve health-care delivery.
      We previously engaged patients, caregivers, health-care providers (HCPs) and
      policymakers in identifying priorities for chronic kidney disease (CKD) research.
      OBJECTIVE: We aimed to explore participants' views on the research priorities and
      prioritization process 2 years after the exercise took place. DESIGN: In this
      qualitative descriptive study, individual interviews were conducted and analysed
      using an inductive, thematic analysis approach. SETTING/PARTICIPANTS:
      Participants resided across Canada. We purposively sampled across stakeholder
      groups (CKD patients, caregivers, HCPs and policymakers) and types of engagement
      (wiki, workshop and/or steering committee) from the previous CKD priority-setting
      project. RESULTS: Across 23 interviews, participants discussed their research
      priorities over time, views on the prioritization process and perceived
      applicability of the priorities. Even though their individual priorities may have
      changed, participants remained in agreement overall with the previously
      identified priorities, and some perceived a distinction between patient and HCP
      priorities. They tended to balance individual priorities with their broader
      potential impact and viewed the prioritization process as systematic,
      collaborative and legitimate. However, participants acknowledged challenges to
      applying the priorities and emphasized the importance of communicating the
      project's outcomes upon its completion. CONCLUSION: Two years after engaging in
      CKD research prioritization, stakeholder participants remained in agreement with
      the previously identified priorities, which they felt reflected group
      deliberation and consensus. Rapport and communication were highlighted as key
      elements supporting effective engagement in research prioritization.

PMID- 30112821
TI  - Customizable Lipid Nanoparticle Materials for the Delivery of siRNAs and mRNAs.
AB  - RNAs are a promising class of therapeutics given their ability to regulate
      protein concentrations at the cellular level. Developing safe and effective
      strategies to deliver RNAs remains important for realizing their full clinical
      potential. Here, we develop lipid nanoparticle formulations that can deliver
      short interfering RNAs (for gene silencing) or messenger RNAs (for gene
      upregulation). Specifically, we study how the tail length, tail geometry, and
      linker spacing in diketopiperazine lipid materials influences LNP potency with
      siRNAs and mRNAs. Eight lipid materials are synthesized, and 16 total
      formulations are screened for activity in vitro; the lead material is evaluated
      with mRNA for in vivo use and demonstrates luciferase protein expression in the
      spleen. In undertaking this approach, not only do we develop synthetic routes to
      delivery materials, but we also reveal structural criteria that could be useful
      for developing next-generation delivery materials for RNA therapeutics.

PMID- 30112822
TI  - The negative effects of habitat fragmentation operate at the scale of dispersal.
AB  - Habitat loss is often considered the greatest near-term threat to biodiversity.
      Yet the impact of habitat fragmentation, or the change in habitat configuration
      for a given amount of habitat loss, has been intensely debated. We isolated
      effects of habitat loss from fragmentation on the demography, movement, and
      abundance of wild populations of a specialist herbivore, Chelinidea vittiger, by
      removing 2,088 patches across 15 landscapes. We compared fragmentation resulting
      from random loss, which is often considered in theory, to aggregated loss, which
      is often observed in the real world. When quantifying fragmentation caused by
      random vs. aggregated loss, aggregated loss led to less fragmented landscapes
      than random loss based on patch isolation, but more fragmented landscapes when
      based on isolation at a larger mesoscale scale defined by dispersal distances of
      C. vittiger. Overall, habitat loss decreased population size and demographic
      parameters, with thresholds occurring at approximately 70-80% patch loss.
      Synergistic effects also occurred, where an aggregated pattern of loss had
      negative effects at low, but not high, amounts of habitat loss. Effects on
      population size of C. vittiger were driven by reductions in movement and
      subsequent reproduction. The direction of habitat fragmentation effects from
      random and aggregated loss treatments, for a given habitat amount, was
      conflictingly positive or negative depending on the scale at which fragmentation
      was quantified. Fragmentation quantified at the scale of dispersal for this
      species best explained population size and highlighted that fragmentation had
      negative effects at a mesoscale. Our results emphasize the importance of
      quantifying habitat fragmentation at biologically appropriate scales.

PMID- 30112823
TI  - Optimal placement of Burow's triangles for aesthetically pleasing repair of
      multiple defects using local flaps after tumor excision.

PMID- 30112824
TI  - Dissemination of enteroviruses in the production chain of organic lettuce in Rio
      de Janeiro, Brazil.
AB  - This study aimed to survey the environmental dissemination of enterovirus (EV) in
      a site of organic lettuce situated in the mountainous region of the state of Rio
      de Janeiro, Brazil. For this purpose, a total of 96 environmental samples,
      including water and lettuce samples obtained in different stages of the
      production chain (e.g., irrigation water, seedlings, lettuces grown, and washed
      lettuces ready-to-eat), were analyzed. EV genomes were detected in 12.5% (12/96)
      of the tested samples (eight from irrigation water and 4 from lettuce samples).
      Levels of viral concentration ranged from 3.37 * 103 to 4.72 * 106 genomic copies
      per liter (gc L-1 ) and from 2.14 * 104 to 5.56 * 104 genome copies per 25 grams
      (gc 25 g-1 ) for the water and lettuce samples, respectively. Such findings
      suggest that the use of viruses as human fecal contamination markers must be
      considered in order to improve food safety in organic supply chains.

PMID- 30112825
TI  - Analysis of longitudinal data from outcome-dependent visit processes: Failure of
      proposed methods in realistic settings and potential improvements.
AB  - The timing and frequency of the measurement of longitudinal outcomes in databases
      may be associated with the value of the outcome. Such visit processes are termed
      outcome dependent, and previous work showed that conducting standard analyses
      that ignore outcome-dependent visit times can produce highly biased estimates of
      the associations of covariates with outcomes. The literature contains several
      classes of approaches to analyze longitudinal data subject to outcome-dependent
      visit times, and all of these are based on simplifying assumptions about the
      visit process. Based on extensive discussions with subject matter investigators,
      we identified common characteristics of outcome-dependent visit processes that
      allowed us to evaluate the performance of existing methods in settings with more
      realistic visit processes than have been previously investigated. This paper uses
      the analysis of data from a study of kidney function, theory, and simulation
      studies to examine a range of settings that vary from those where all visits have
      a low degree of missingness and outcome dependence (which we call "regular"
      visits) to those where all visits have a high degree of missingness and outcome
      dependence (which we call "irregular" visits). Our results show that while all
      the approaches we studied can yield biased estimates of some covariate effects,
      other covariate effects can be estimated with little bias. In particular, mixed
      effects models fit by maximum likelihood yielded little bias in estimates of the
      effects of covariates not associated with the random effects and small bias in
      estimates of the effects of covariates associated with the random effects. Other
      approaches produced estimates with greater bias. Our results also show that the
      presence of some regular visits in the data set protects mixed model analyses
      from bias but not other methods.

PMID- 30112826
TI  - A systematic review of clinicians' views and experiences of direct-acting oral
      anticoagulants in the management of nonvalvular atrial fibrillation.
AB  - AIMS: While a plethora of systematic reviews have provided evidence of efficacy,
      effectiveness and safety of direct-acting oral anticoagulants (DOACs) in the
      management of nonvalvular atrial fibrillation, there has been little emphasis on
      clinicians' perspectives. This systematic review aimed to critically appraise,
      synthesize and present the available evidence of clinicians' views and
      experiences. METHODS: Studies published in English from January 2006 to July 2017
      reporting the views and/or experiences of doctors, nurses or pharmacists on any
      individual DOAC or as a pharmacological group were included. Studies were
      assessed for quality by two researchers, data extracted and findings synthesized
      using a narrative approach. RESULTS: Following exclusion of duplicates, 777
      titles, 394 abstracts and 196 studies were screened. Ten studies were included in
      the review, nine of which were quantitative (cross-sectional surveys) and one
      qualitative (semistructured interviews), with marked heterogeneity in outcomes
      reported. Studies were conducted exclusively in Europe and the USA. In those
      studies reporting clinician preference, DOACs were first choice over warfarin in
      naive patients, based on perceptions of evidence of effectiveness equivalent or
      superior to warfarin and superior safety. Other advantageous factors were in
      those with an unstable International Normalized Ratio and likely to miss
      appointments. There were, however, concerns relating to management of over
      anticoagulation and experiences of observed bleeding rates. CONCLUSION: There is
      a limited evidence base of clinicians' perspectives of DOACs, necessitating
      further research, particularly given the trajectory of increased use worldwide.

PMID- 30112827
TI  - Do Skilled Nursing Facilities Selected to Participate in Preferred Provider
      Networks Have Higher Quality and Lower Costs?
AB  - OBJECTIVE: To determine whether skilled nursing facilities (SNFs) chosen by
      health systems to participate in preferred provider networks exhibited
      differences in quality, costs, and patient outcomes relative to other SNFs after
      accounting for differences in case mix. DATA SOURCES: Medicare provider and
      claims data, 2012 and 2013. STUDY DESIGN: We compared SNFs included in preferred
      networks relative to other SNFs in the same market, prior to the establishment of
      preferred provider networks. DATA EXTRACTION METHODS: We linked the SNFs in our
      sample to facility characteristics and quality data. We identified SNF admissions
      and hospitalizations in claims data and limited the analysis to patients
      discharged from the hospitals in our sample. We obtained patient characteristics
      from Medicare summary files and the preceding hospital stay. PRINCIPAL FINDINGS:
      Preferred SNFs exhibited better performance across publicly reported quality
      measures. Patients admitted to preferred SNFs exhibited shorter stays, lower
      Medicare payments, and lower probability of SNF readmission relative to
      nonpreferred SNFs. CONCLUSIONS: Our results imply that health systems selected
      SNFs with lower resource use and better performance on quality measures. Thus,
      the trend toward preferred provider networks could have implications for Medicare
      spending and patient health.

PMID- 30112828
TI  - Aerobic Oxidation of Primary Amines to Imines in Water using a Cobalt Complex as
      Recyclable Catalyst under Mild Conditions.
AB  - Oxidative coupling of primary amines to imines has been achieved by using a water
      soluble cobalt complex as catalyst and air as the oxidant at near ambient
      conditions. Aromatic, heteroaromatic and aliphatic amines were successfully
      converted to the corresponding imines with yields of up to 96 %. A 20 gram scale
      reaction for the synthesis of imine from benzylamine in good yield is also
      demonstrated with this method. The catalyst has been found to be reusable with up
      to five cycles. It is highly efficient, gives a turnover number (TON) of up to
      128, and shows chemoselectivity with the only byproducts being water and ammonia.
      Control experiments and mechanistic studies indicate that the CoII /CoIII
      catalytic cycle is responsible for these oxidative transformations. Some of the
      reactive intermediates of this reaction have also been isolated and structurally
      characterized.

PMID- 30112829
TI  - Autocatalytic Synthesis of Bifluoride Ionic Liquids by SuFEx Click Chemistry.
AB  - Ionic liquids with bifluoride anions possess properties such as high
      conductivity, wide electrochemical windows, and low viscosity that make them
      attractive materials for various electrochemical devices. However, owing to the
      lack of reliable synthetic routes, bifluoride-based ionic liquids have seldom
      been explored. Herein, an autocatalytic strategy for the HF-free synthesis of
      bifluoride-based sulfonamide ionic liquids based on the sulfur(VI) fluoride
      exchange (SuFEx) reaction is reported. This reaction requires no chromatographic
      purification, and yields are quantitative. The thermophysical properties (phase
      transition behavior and decomposition temperature) and electrochemical
      stabilities of the resulting products were studied. The products with alkyl,
      aryl, and perfluoroalkyl side chains exhibited extraordinarily wide
      electrochemical windows (up to 6.0 V) with reproducible results among multiple
      replicate measurements.

PMID- 30112830
TI  - Is there a role for von Willebrand factor/factor VIII concentrate supplementation
      in complex congenital heart surgery?

PMID- 30112831
TI  - Michigan Emergency Department Leader Attitudes Toward and Experiences With
      Clinical Pathways to Guide Admission Decisions: A Mixed-methods Study.
AB  - OBJECTIVES: The objective was to characterize emergency department (ED) leader's
      attitudes toward potentially avoidable admissions and experiences with the use of
      clinical pathways to guide admission decisions, including the challenges and
      successes with implementation of these pathways. METHODS: A mixed-methods study
      of Michigan ED leaders was conducted. First, a cross-sectional Web-based survey
      was distributed via e-mail to all 135 hospital-based EDs in the state.
      Descriptive statistics were calculated. Survey participants who provided contact
      information were considered eligible for follow-up. Semistructured interviews
      were conducted by telephone until thematic saturation was reached. Interviews
      were recorded, transcribed verbatim, reviewed for accuracy, and thematically
      coded. Representative quotes were extracted for reporting. RESULTS: Survey
      responses were received from 64 ED leaders (48% eligible response rate).
      Semistructured interviews were conducted with a purposeful sample of 11 of the 29
      representatives willing to be contacted. Eight sites implemented clinical care
      pathways as a strategy to reduce avoidable admissions. Pathways were developed
      for high-frequency conditions. Many pathways were multidisciplinary,
      incorporating case managers and outpatient care providers, which was thought to
      improve acceptability. Five models of care emerged 1) standardized care, 2)
      observation medicine, 3) enhanced follow-up, 4) care coordination, and 5)
      comprehensive programs. We identified barriers to and facilitators of discharging
      a patient from the ED when an admission otherwise could be avoided. Barriers
      included limited access to follow-up, lack of care coordination, and lack of
      trust in patient's ability to provide self-care or navigate the system.
      Facilitators included strong relationships with outpatient providers, care
      coordination, and shared decision making. CONCLUSIONS: Potential solutions to
      help avoid hospitalization from the ED include multidisciplinary clinical care
      pathways. Successful pathways emerged from bringing stakeholders from the ED,
      hospital, and health care community together. Additionally, emergency providers
      need systems and supports in place to help their patients navigate follow-up care
      in a timely fashion.

PMID- 30112832
TI  - Cutaneous Langerhans cell histiocytosis - an indication for dermatological
      pharmacotherapy with topical nitrogen mustard.

PMID- 30112833
TI  - Accuracy of cone-beam computed tomography, dental magnetic resonance imaging, and
      intraoral radiography for detecting peri-implant bone defects at single zirconia
      implants-An in vitro study.
AB  - OBJECTIVES: To evaluate the diagnostic value of cone-beam computed tomography
      (CBCT), intraoral radiography (IR), and dental magnetic resonance imaging (dMRI)
      for detecting and classifying peri-implant bone defects at zirconia implants.
      MATERIALS AND METHODS: Forty-eight zirconia implants were inserted in bovine
      ribs, 24 of which had standardized defects (1-wall, 2-wall, 3-wall, 4-wall) in
      two sizes (1 and 3 mm). CBCT, IR, and dMRI were performed and analyzed twice by
      four readers unaware of the nature of the defects. Cohen's and Fleiss' kappa
      (kappa), sensitivity, and specificity were calculated for the presence/absence of
      bone defects, defect size, and defect type. Cochran's Q-test with post hoc
      McNemar was used to test for statistical differences. RESULTS: A high intra- and
      inter-reader reliability (kappa range: 0.832-1) and sensitivity/specificity (IR:
      0.97/0.96; CBCT: 0.99/1; dMRI: 1/0.99) for bone defect detection were observed
      for all three imaging methods. For defect type classification, intra- (kappa
      range: 0.505-0.778) and inter-reader (kappa: 0.411) reliability of IR were lower
      compared to CBCT (kappa range intrareader: 0.667-0.889; kappa inter-reader:
      0.629) and dMRI (kappa range intrareader: 0.61-0.832; kappa inter-reader: 0.712).
      The sensitivity for correct defect type classification was not significantly
      different for CBCT (0.81) and dMRI (0.83; p = 1), but was significantly lower for
      IR (0.68; vs. CBCT p = 0.003; vs. dMRI p = 0.004). The sensitivity advantage of
      CBCT and dMRI for defect classification was smaller for 1-mm defects
      (CBCT/dMRI/IR: 0.68/0.72/0.63, no significant difference) than for 3-mm defects
      (CBCT/dMRI/IR: 0.95/0.94/0.74; CBCT vs. IR p = 0.0001; dMRI vs. IR p = 0.003).
      CONCLUSION: Within the limitations of an in vitro study, IR can be recommended as
      the initial imaging method for evaluating peri-implant bone defects at zirconia
      implants. CBCT provides higher diagnostic accuracy of defect classification at
      the expense of higher cost and radiation dose. Dental MRI may be a promising
      imaging method for evaluating peri-implant bone defects at zirconia implants in
      the future.

PMID- 30112834
TI  - A Preview of Selected Articles.

PMID- 30112836
TI  - RING finger protein 38 induces gastric cancer cell growth by decreasing the
      stability of the protein tyrosine phosphatase SHP-1.
AB  - The function of the E3 ligase RNF38 is still unknown in gastric cancer. Here, we
      found that RNF38 is upregulated in gastric cancer, and it is associated with the
      overall survival of gastric cancer patients. Further studies showed that RNF38
      interacts with the nonreceptor tyrosine phosphatase SH2-containing protein
      tyrosine phosphatase 1 (SHP-1) and induces the polyubiquitination of SHP-1, which
      leads to destabilization of SHP-1 and promotion of STAT3 signaling in gastric
      cancer cells. In addition, overexpression or knockdown of RNF38 induces or
      suppresses gastric cancer cell growth in vitro, respectively, and silencing RNF38
      delays tumor growth in vivo. These findings demonstrate that RNF38 is functional
      in gastric cancer and promotes STAT3 signaling by destabilizing SHP-1; thus,
      RNF38 could be a novel target for gastric cancer therapy.

PMID- 30112835
TI  - Incidence and determinants of spontaneous hepatitis B surface antigen
      seroclearance and seroconversion in hepatitis B e antigen-negative chronic
      infection patients: A population-based prospective cohort.
AB  - Seroclearance of hepatitis B surface antigen (HBsAg) has been widely studied;
      however, seroconversion of HBsAg and characteristics of viral load among
      hepatitis B e antigen (HBeAg)-negative chronic infection patients after HBsAg
      lost is not clear. We performed a large-scale study in a HBeAg-negative chronic
      infection cohort to evaluate spontaneous HBsAg seroclearance incidence from
      October 2012 to April 2017 in Jiangsu province, China. We also elucidated the
      characteristics of HBsAg seroconversion and hepatitis B virus (HBV) DNA
      detectability among patients who cleared HBsAg. A total of 2997 HBeAg-negative
      chronic infection patients (mean age 52.3 +/- 12.9 years at baseline) were
      included. With 10 519 person-years of follow-up, 348 patients successfully
      spontaneously cleared HBsAg, with an incidence rate of 3.31 per 100 person-years.
      Patients with HBV DNA detectable ~1999 IU/mL at baseline had a lower probability
      of HBsAg seroclearance relative to those with undetectable HBV DNA, with a hazard
      ratio of 0.31 (95% CI = 0.23, 0.41). HBsAg seroconversion occurred in 37.3% of
      those patients who cleared HBsAg. The geometric mean of anti-HBs among those with
      HBsAg conversion was 79.4 mIU/mL. Female had a higher HBsAg seroconversion rate
      (P = 0.011). Among those with HBsAg seroclearance, 11.2% still had HBV DNA levels
      of higher than 100 IU/mL. Patients with higher HBV DNA at baseline had a higher
      risk of detectable HBV DNA levels even after HBsAg seroclearance (P < 0.001).
      This study reveals HBsAg seroconversion rates and HBV DNA undetectability
      epidemiological characteristics of patients with HBsAg seroclearance and suggests
      that monitoring HBV DNA is needed when managing HBeAg-negative chronic patients,
      even after clearing HBsAg.

PMID- 30112837
TI  - Phase Behavior of Bowl-Shaped Colloids: Order and Dynamics in Plastic Crystals
      and Glasses.
AB  - Charged fluorescent bowl-shaped colloids consisting of a polystyrene core
      surrounded by a poly(N-isopropylmethacrylamide) shell are obtained by
      nanoengineering spherical composite microgels. The phase diagram of these soft
      bowl-shaped colloids interacting through long-range Yukawa-type interactions is
      investigated using confocal laser scanning microscopy. The bowl-shaped structure
      leads to marked differences in phase-behavior compared to their spherical
      counterpart. With increasing number density, a transition from a fluid to a
      plastic crystal phase, with freely rotating particles, followed by a glass-like
      state is observed. It is found that the anisotropic bowl shape frustrates
      crystallization and slows down crystallization kinetics and causes the glass-like
      transition to shift to a significantly lower volume fraction than for the
      spheres. Quantitative analysis of the positional and orientational order
      demonstrates that the plastic crystal phase exhibits quasi-long range
      translational order and orientational disorder, while in the disordered glass
      like phase the long-range translational order vanishes and short-range rotational
      order appears, dictated by the specific bowl shape. It is further shown that the
      different structural transitions are characterized by decoupling of the
      translational and orientational dynamics.

PMID- 30112838
TI  - Single arm two-stage studies: Improved designs for molecularly targeted agents.
AB  - Mechanistic understanding of cancers and their potential interactions with
      molecularly targeted agents is driving the need for stratified medicine to ensure
      each participant receives the best possible care. This understanding, backed by
      scientific research, should be used to guide the design of clinical trials for
      these agents. The mechanism of action of a molecularly targeted agent often
      suggests that a biomarker can be used as a predictor of activity of the agent on
      the targeted disease. A biomarker driven trial is needed to confirm that the
      molecularly targeted agent stratifies the participant population with disease
      into high and low responder groups. We assume that the biomarker of interest can
      be dichotomised and propose a balanced parallel two-stage single-arm phase II
      trial that builds on existing two-stage single-arm designs. A single-arm trial
      cannot distinguish between a marker being predictive in the population as a whole
      and the agent causing an increased response in the marker positive group, but it
      is a first step. We compare this approach to the existing single-arm approaches,
      sequential enrichment, tandem two-stage, and parallel two-stage designs, and
      discuss the advantages and disadvantages of each design. We show that our design
      compares favourably to existing designs in the Bayesian framework, making a more
      efficient use of collected data. We recommend using the parallel two-stage
      balanced or sequential enrichment designs when randomisation is not practical in
      a phase II trial.

PMID- 30112839
TI  - Multi-Stimuli-Responsive Directional Assembly of an Amphiphilic Donor-Acceptor
      Alternating Supramolecular Copolymer.
AB  - The stimuli-responsive supramolecular co-assembly of two pi-amphiphiles, NDI-1
      and Py-1, in which an acceptor (A) (naphthalene diimide) and a donor (D) (pyrene)
      chromophore, respectively, serve as the hydrophobic segment, is described. In
      addition, both contain an amide group in a designated location so that H-bonding
      and D-A charge-transfer (CT) interactions can operate simultaneously. H-bonding
      among the amide groups not only enhanced the CT interaction promoted by the
      alternating D-A stacking propensity, but also fixed the lateral orientation of
      the two chromophores and thus compelled the anionic and nonionic hydrophilic head
      groups, appended with the D and A amphiphiles, respectively, to remain segregated
      on two opposite sides of the amphiphilic alternating supramolecular copolymer.
      This copolymer showed spontaneous polymersome assembly with the D-appended
      anionic groups displayed at the outer surface, whereas the A-appended hydrophilic
      wedge converged at the inner lacuna. In contrast, spherical or cylindrical
      micellar structures were produced by Py-1 and NDI-1, respectively. Effective
      functional-group display in the D-A supramolecular polymersome enabled protein
      surface recognition and inhibition of the enzymatic activity of Cht. Under a
      reducing environment, formation of NDI.- jeopardized the D-A interaction and thus
      the A chromophores were ejected out of the membrane of the polymersome causing
      its gradual contraction in size by >75 %. D-A supramolecular polymersomes also
      exhibited a lower critical solution temperature that could be tuned across a
      temperature window of 40 to 70  degrees C by varying the ratio of the A and D
      components in the alternating supramolecular copolymer.

PMID- 30112840
TI  - Truths and myths in sunscreen labeling.
AB  - The American Academy of Dermatology (AAD) has prioritized skin cancer prevention
      efforts in 2018, as photoprotection measures adopted by the general public remain
      suboptimal. A large proportion of patients lack understanding of primary
      prevention methods for skin cancer, and mistruths in advertising may contribute
      significantly to this deficit. Sunscreen labels are often stacked with multiple
      claims of seemingly high significance, making it difficult for patients to
      differentiate their validity when selecting a sunscreen. The United States Food
      and Drug Administration (FDA) published its monograph in 2011 to address these
      controversies in sunscreen labeling, but the reliability of several other claims
      remain unclear. In this article, we discuss several claims commonly made on
      sunscreen labels, and address the truths and mistruths surrounding them.

PMID- 30112842
TI  - Cobalt-Catalyzed Enantioselective Synthesis of Chiral gem-Bis(boryl)alkanes.
AB  - We report an asymmetric synthesis of enantioenriched gem-bis(boryl)alkanes in an
      enantioselective diborylation of 1,1-disubstituted alkenes catalyzed by Co(acac)2
      /(R)-DM-segphos. A range of activated and unactivated alkenes underwent this
      asymmetric diborylation in the presence of cyclooctene as a hydrogen acceptor,
      affording the corresponding gem-bis(boryl)alkanes with high enantioselectivity.
      The synthetic utility of these chiral organoboronate compounds was demonstrated
      through several stereospecific derivatizations and the synthesis of sesquiterpene
      and sesquiterpenoid natural products.

PMID- 30112843
TI  - Suspect Retinal Detachment? Ocular Ultrasound Can Help.

PMID- 30112844
TI  - Divergent brain gene expression profiles between alternative behavioural helper
      types in a cooperative breeder.
AB  - Juveniles of the cooperatively breeding cichlid fish Neolamprologus pulcher
      either consistently provide help in form of alloparental egg care ("cleaners") or
      consistently abstain from helping ("noncleaners"). These phenotypes are not based
      on heritable genetic differences. Instead, they arise during ontogeny, which
      should lead to differences in brain structure or physiology, a currently untested
      prediction. We compared brain gene expression profiles of cleaners and
      noncleaners in two experimental conditions, a helping opportunity and a control
      condition. We aimed to identify (a) expression differences between cleaners and
      noncleaners in the control, (b) changes in gene expression induced by the
      opportunity and (c) differences in plasticity of gene expression between cleaners
      and noncleaners. Control cleaners and noncleaners differed in the expression of a
      single gene, irx2, which regulates neural differentiation. During the
      opportunity, cleaners and noncleaners had three upregulated genes in common,
      which were implicated in neuroplasticity, hormonal signalling and cell
      proliferation. Thus, the stimulus in the opportunity was sufficiently salient.
      Cleaners also showed higher expression of seven additional genes that were unique
      to the opportunity. One of these cleaner-specific genes is implicated in
      neuropeptide metabolism, indicating that this process is associated with cleaning
      performance. This suggests that the two types employed different pathways to
      integrate social information, preparing them for accelerated reaction to future
      opportunities. Interestingly, three developmental genes were downregulated
      between the control and the opportunity in cleaners only. Our results indicate
      that the two behavioural types responded differently to the helping opportunity
      and that only cleaners responded by downregulating developmental genes.

PMID- 30112845
TI  - Decision support algorithm for the selection of analytical methods in organic
      compounds detection for future extraterrestrial exploratory missions.
AB  - The search for biotic compounds beyond planet Earth is among the highest
      priorities in space discovery. We sought to detect organic molecules in various
      earth soil samples collected from environments with extreme climatic conditions
      comparable to extraterrestrial environments using HPLC, spectrophotometry (UV,
      IR), GC/MS and vertical gel electrophoresis analyses systems. The applied methods
      in the study were compared using a self-developed software tool that was designed
      to evaluate the viability of instrument selection for organics detection in any
      given exploratory mission. The tool was created to aid further development and
      refinements of rapidly improving technological solutions such as MCE and MS
      instruments. Such comparison can be done quickly and easily, acting as a decision
      support tool when choosing between analytical methods during any planning phase
      of future exploration missions led by space agencies (i.e., NASA).

PMID- 30112841
TI  - Long-term risk of cardiovascular mortality in lymphoma survivors: A systematic
      review and meta-analysis.
AB  - Cardiovascular disease has been identified as one of the late complications of
      cancer therapy. The purpose of this study was to quantify the long-term risk of
      cardiovascular mortality among lymphoma survivors relative to that of the general
      population. A systematic review and meta-analysis were conducted. Articles were
      identified in November 2016 by searching EMBASE, MEDLINE, and CINAHL databases.
      Observational studies were included if they assessed cardiovascular mortality in
      patients with lymphoma who survived for at least 5 years from time of diagnosis
      or if they had a median follow-up of 10 years. A pooled standardized mortality
      ratio (SMR) was estimated using a DerSimonian and Laird random-effects model. The
      Q and I2 statistics were used to assess heterogeneity. Funnel plots and Begg's
      and Egger's tests were used to evaluate publication bias. Of the 7450 articles
      screened, 27 studies were included in the systematic review representing 46 829
      Hodgkin and 14 764 non-Hodgkin lymphoma survivors. The pooled number of deaths
      attributable to cardiovascular disease among Hodgkin and non-Hodgkin disease was
      estimated to be 7.31 (95% CI: 5.29-10.10; I2  = 95.4%) and 5.35 (95% CI: 2.55
      11.24; I2  = 94.0%) times that of the general population, respectively. This
      association was greater among Hodgkin lymphoma survivors treated before the age
      of 21 (pooled SMR = 13.43; 95% CI: 9.22-19.57; I2  = 78.9%). There was a high
      degree of heterogeneity and a high risk of bias due to confounding in this body
      of literature. Lymphoma survivors have an increased risk of fatal cardiovascular
      events compared to the general population and should be targeted for
      cardiovascular screening and prevention campaigns.

PMID- 30112847
TI  - A Bayesian hierarchal modeling approach to shortening phase I/II trials of
      anticancer drug combinations.
AB  - In phase I/II anticancer drug-combination trials, trial design to evaluate
      toxicity and efficacy has been studied by dividing the trial into 2 stages,
      followed by seamless execution of the 2 stages. In the first stage, admissible
      dose combinations in toxicity are identified, followed by patient assignment
      among the identified admissible dose combinations using adaptive randomization in
      the second stage. When patients are assigned using adaptive randomization, it is
      desirable to determine a more appropriate dose combination by taking into
      consideration both drug efficacy and toxicity; however, during the course of this
      determination and evaluation of toxicity and efficacy, there remains a concern
      that the trial duration might be prolonged. Therefore, we proposed a trial design
      to assign patients adaptively to more appropriate dose combinations in both
      toxicity and efficacy and to shorten trial duration without compromising trial
      performance. When selecting the dose combination for subsequent cohorts,
      unobserved data are treated as missing data, which are imputed using a data
      augmentation algorithm involving a gamma process. Probabilities associated with
      toxicity and efficacy are estimated applying a Bayesian hierarchical model to the
      imputed data, thereby allowing more patients to be assigned more appropriate dose
      combinations in both toxicity and efficacy through adaptive randomization.
      Results of simulation studies suggested that the proposed approach shortened
      trial duration without significantly compromising the performance of the trial as
      compared with existing approaches. We believe that the proposed approach will
      expedite drug development time and reduce costs associated with clinical
      development.

PMID- 30112846
TI  - Intravenous Infusion of Umbilical Cord Blood-Derived Mesenchymal Stem Cells in
      Rheumatoid Arthritis: A Phase Ia Clinical Trial.
AB  - Based on immunomodulatory actions of human umbilical cord blood-derived
      mesenchymal stem cells (hUCB-MSCs), in vitro or preclinical studies of hUCB-MSCs
      have been conducted extensively in rheumatoid arthritis (RA). However, few human
      trials have investigated the outcomes of hUCB-MSC infusions. The CURE-iv trial
      was a phase I, uncontrolled, open label trial for RA patients with moderate
      disease activity despite treatment with methotrexate. The patients received a
      single intravenous infusion of 2.5 * 107 , 5 * 107 , or 1 * 108 cells of hUCB
      MSCs for 30 minutes, three patients in each cluster, with an increment of cell
      numbers when there was no dose-limited adverse event. Clinical and safety
      assessments were performed during the study period, and serum cytokines were
      measured at baseline and 24 hours after the infusion. Out of 11 screened RA
      patients, 9 were enrolled. The participants were predominantly female (78%) and
      the mean age was 57.4 years. The mean disease duration was 9.5 years, and
      baseline 28-joint disease activity score (DAS28; using erythrocyte sedimentation
      rate) was 4.53. There was no major toxicity in all clusters up to 4 weeks after
      the infusion. Serum erythrocyte sedimentation rate changes at 4 weeks (n = 9)
      were -7.9 +/- 10.4 (p = .0517) and DAS28 changes were -1.60 +/- 1.57 (p = .0159).
      Reduced levels of IL-1beta, IL-6, IL-8, and TNF-alpha at 24 hours were observed
      in the cluster infused with 1 * 108 MSCs. This phase Ia hUCB-MSC infusion trial
      for established RA patients revealed no short-term safety concerns. Stem Cells
      Translational Medicine 2018.

PMID- 30112848
TI  - Protease activated-receptor 4 activation as a model of persistent bladder pain:
      Essential role of macrophage migration inhibitory factor and high mobility group
      box 1.
AB  - OBJECTIVES: To develop a rodent model of persistent non-inflammatory bladder pain
      and to test macrophage migration inhibitory factor and high mobility box group 1
      as mediators of bladder pain. METHODS: Female C57BL/6 mice received intravesical
      instillations of protease activated receptor 4 (100 MUmol/L, for 1 h) three times
      every other day and abdominal mechanical hypersensitivity (50% mechanical
      threshold) was tested on day 0 (baseline), and at days 1, 2, 3, 4, 7 and 9 after
      the first protease-activated receptor 4 injection. At the end of the experiment,
      micturition changes were measured and bladders were examined for histological
      changes. Macrophage migration inhibitory factor antagonist (MIF098; 40 mg/kg i.p.
      b.i.d.) or high mobility group box 1 inhibitor (glycyrrhizin; 50 mg/kg i.p.
      daily) was administered from day 2 until day 8. RESULTS: There was a significant
      and persistent decrease in abdominal mechanical threshold starting from day 3 in
      the protease-activated receptor 4-treated group that persisted until day 9 (5
      days post-last instillation), but not in the control group. Glycyrrhizin fully
      reversed while MIF098 partially reversed abdominal mechanical hypersensitivity in
      protease-activated receptor 4-treated mice. The changes started on day 3 after
      the first protease-activated receptor 4 instillation, and analgesic effects
      lasted throughout the rest of the testing period. None of the groups had
      significant micturition changes or overt bladder histological changes.
      CONCLUSIONS: Repeated intravesical protease activated receptor 4 instillations
      produce persistent bladder pain without inflammation. Macrophage migration
      inhibitory factor and high mobility group box 1 are possible effective target
      molecules for bladder pain alleviation.

PMID- 30112849
TI  - Disparities in mortality for chronic liver disease among Asian subpopulations in
      the United States from 2007 to 2016.
AB  - The Asian American population is characterized by remarkable diversity. Studying
      Asians as an aggregate group may obscure clinically meaningful heterogeneity. We
      performed a population-based study using data from the US National Vital
      Statistics System. We determined the trends in age-standardized mortality rates
      for chronic liver disease stratified by aetiology among the most populous US
      based Asian subgroups (Asian Indians, Chinese, Filipino, Japanese, Korean and
      Vietnamese) and compared it to non-Hispanic whites. Annual percentage change was
      calculated to determine temporal mortality patterns using joinpoint analysis.
      Hepatitis C virus-related mortality rates were higher in non-Hispanic whites
      compared to individual Asian subgroups, but a sharp decline in mortality rates
      was noted in 2014 among non-Hispanic whites and all Asian subgroups. Age
      standardized hepatitis B virus-related mortality rates were higher in all Asian
      subgroups as compared to non-Hispanic whites in 2016, with the highest mortality
      among Vietnamese followed by Chinese. Mortality rates for alcoholic liver disease
      have been steadily trending upwards in all Asian subgroups, with the highest
      mortality in Japanese. Overall, age-standardized cirrhosis-related mortality
      rates were highest in non-Hispanic whites, followed by Japanese, and more
      distantly by Vietnamese and other subgroups. However, hepatocellular carcinoma
      related mortality rates were higher in most Asian subgroups led by Vietnamese,
      Japanese and Koreans compared to non-Hispanic whites. In this population-based
      study utilizing a nationally representative database, we demonstrated a marked
      heterogeneity in the mortality rates of aetiology-specific chronic liver disease
      among Asian subgroups in the United States.

PMID- 30112851
TI  - Sources of health financing and health outcomes: A panel data analysis.
AB  - We study the differential impacts of public and private sources of health
      spending on health outcomes using a triple difference approach. We find that
      private health spending has on average a higher health-promoting effect than
      public health spending. This result is robust with respect to the choice of
      outcome measure and covariates in the regression and driven primarily by the
      countries with ineffective governments. Once we restrict our sample to countries
      with effective governments, private health spending is found to be no better than
      public health spending in improving the health outcome.

PMID- 30112850
TI  - Structure-Mediated Charge Separation in Boron Carbon Nitride for Enhanced
      Photocatalytic Oxidation of Alcohol.
AB  - Boron carbon nitride (BCN) is a promising earth-abundant photocatalyst for solar
      energy conversion. However, the photocatalytic activities of BCN materials remain
      moderate because of the fast electron-hole recombination. Herein, an ordered BCN
      structure is fabricated by a facile one-step thermal treatment strategy. The
      ordered structure of BCN is directly evident from powder X-ray diffraction and
      high-resolution transmission electron microscopy. Importantly, it is found that
      the long-period ordered structure can intrinsically accelerate the separation and
      transfer kinetics of photogenerated charge carriers. Benefiting from these
      advantages, the ordered BCN structure exhibits remarkable performance for
      photoinduced selective oxidation of benzyl alcohol compared with the pristine BCN
      counterpart. This work highlights the important role of the crystal structure of
      light-harvesting materials in affecting electron-hole separation and at the same
      time points to the ample potential for improving the photocatalytic performance.

PMID- 30112852
TI  - Behaviors of shooter and goalkeeper interact to determine the outcome of soccer
      penalties.
AB  - During a soccer penalty, the shooter's strategy and the goalkeeper's strategy
      interact to determine the outcome. However, most models of penalty success
      overlook its interactive nature. Here, we quantified aspects of shooter and
      goalkeeper strategies that interact to influence the outcome of soccer penalties
      namely, how the speed of the shot affects the goalkeeper's leave time or shot
      blocking success, and the effectiveness of deceptive strategies. We competed 7
      goalkeepers and 17 shooters in a series of penalty shoot-out competitions with a
      total of 1278 shots taken. Each player was free to use any strategy within the
      rules of a penalty shot, and game-like pressure was created via monetary
      incentive for goal-scoring (or blocking). We found that faster shots lead to
      earlier leave times and were less likely blocked by goalkeepers, and-unlike most
      previous studies-that deceptive shooting strategies did not decrease the
      likelihood goalkeepers moved in the correct direction. To help identify optimal
      strategies for shooters and goalkeepers, we generated distributions and
      mathematical functions sport scientists can use to develop more comprehensive
      models of penalty success.

PMID- 30112853
TI  - Defects in centromeric/pericentromeric histone H2A T120 phosphorylation by hBUB1
      cause chromosome missegregation producing multinucleated cells.
AB  - Histone H2A phosphorylation plays a role both in chromatin condensation during
      mitosis and in transcriptional activation during the G1/S transition. Bub1 and
      NHK1/VRK1 have been identified as histone H2A kinases. However, little is known
      about the importance of histone H2A phosphorylation in chromosome segregation.
      Here, we expressed recombinant hBUB1 and confirmed that it phosphorylates histone
      H2A T120 in the in vitro-assembled nucleosome. Knockdown (KD) of BUB1 decreases
      bulk H2A T120 phosphorylation in HeLa cells, whereas hBUB1 is upregulated during
      mitosis, which corresponds with H2A T120 phosphorylation. ChIP-qPCR of the DXZ1
      centromeric and gamma-ALR pericentromeric region showed that BUB1 localizes to
      this region and increases local H2A T120 phosphorylation during M phase. BUB1 KD
      did not induce apoptosis but increased the M phase cell population, as detected
      by flow cytometry. BUB1 KD also caused an abnormal metaphase and telophase,
      resulting in multinucleated cells and impaired cancer cell growth both in vitro
      and in vivo. Over-expression of the histone H2A T120D or T120E mutations, which
      mimic phosphorylated threonine, decreased the number of multinucleated cells
      caused by BUB1 KD. These results strengthen the apparent importance of BUB1
      mediated H2A T120 phosphorylation in normal mitosis.

PMID- 30112854
TI  - Lack of reduction in serum alpha-fetoprotein during treatment with direct
      antiviral agents predicts hepatocellular carcinoma development in a large cohort
      of patients with hepatitis C virus-related cirrhosis.
AB  - Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients
      treated with direct-acting antiviral agents (DAA) is still debating. We
      investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients
      who completed treatment with DAA, with a median follow-up of 17.3 months after
      end of treatment (EOT), including 943 patients without history of HCC and 102
      previously treated for HCC. The majority were men (59.9%), with compensated
      cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and
      Kaplan-Meier curves were performed to detect predictors of HCC in patients with
      and without reduction in alpha-fetoprotein (AFP) during treatment. SVR12 was
      95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of
      102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and
      curable (P = 0.03). AFP decreased from 16.1 +/- 36.2 mg/dL (baseline) to 11.4 +/-
      55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older
      age, higher model for end-stage liver disease, prolonged INR, lower platelets,
      baseline and EOT AFP, virological failure and no reduction in AFP during
      treatment. Kaplan-Meier curves showed lower incidence of HCC in patients showing
      any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P
      = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99-1.00),
      previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89-19.34) and no reduction in
      AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60-5.54) were independent
      predictors of HCC. In conclusion, risk of HCC after DAA treatment remains
      substantial. It is higher among patients with previous HCC, low platelets and
      without reduction in AFP during treatment.

PMID- 30112855
TI  - Blood glucose profiles in East Asian and Caucasian injection-naive patients with
      type 2 diabetes inadequately controlled on oral medication: a pooled analysis.
AB  - AIM: The primary objective of this study was to compare blood glucose (BG)
      excursions between East Asian and Caucasian patients with type 2 diabetes
      mellitus (T2DM) who were injection-naive, had inadequate glycemic control with
      oral antihyperglycemic medications, and who required initiation with injectable
      therapy. METHODS: This retrospective pooled analysis included individual patient
      data from completed clinical trials (Insulin lispro injection/dulaglutide
      development programs, first patient visit >=1997). All included patients were
      >=18 years, were East Asian or Caucasian, and had data for self-monitored BG at
      baseline. The primary outcome, BG excursion at baseline (least-squares mean,
      standard error), was compared between patient groups using an analysis of
      covariance with race as the fixed effect. Independent covariates included
      baseline body weight, baseline HbA1c, age, and duration of T2DM. RESULTS:
      Caucasian (n = 6779) and East Asian (n = 1638) patients from 21 trials were
      included. BG excursions were significantly higher for East Asian than Caucasian
      patients at breakfast (4.03 [0.075] vs 2.59 [0.045] mmol/L), lunch (3.37 [0.080]
      vs 1.43 [0.049] mmol/L), and dinner (3.16 [0.080] vs 1.74 [0.047] mmol/L) (P <
      0.001 adjusted analyses). Similar findings were observed for the unadjusted
      analyses. At each time point, postprandial BG was significantly higher for East
      Asian than Caucasian patients (with adjusted and unadjusted analyses).
      CONCLUSION: These findings suggest that BG excursion and postprandial BG are
      higher among East Asian patients with T2DM than Caucasian patients. In addition,
      these findings may help clinicians select appropriate treatments for East Asian
      patients with T2DM who require injection therapy.

PMID- 30112856
TI  - Evaluating the thrombin generation profiles of four different rFVIII products in
      FVIII-deficient plasma using FIXa and FXIa activation.
AB  - INTRODUCTION: The thrombin generation assay (TGA) can be used to monitor factor
      replacement therapy in patients with haemophilia. The TGA assay is typically
      performed using tissue factor as the reaction activator; however, activating with
      FIXa or FXIa can enhance assay sensitivity when FVIII < 1%. AIMS: To evaluate the
      sensitivity of the TGA when FIXa (5 nmol/L) and FXIa (0.22 nmol/L) are used to
      activate the assay in platelet-poor plasma and to compare these data to the one
      stage and chromogenic assays. METHODS: Plasma from 10 severe FVIII-deficient
      subjects was supplemented with FVIII (0%, 0.1%, 0.4%, 1.2%, 4%, 11% and 33%),
      using either Novo Eight(r) , Advate(r) , Eloctate(r) , turoctocog alfa pegol or a
      control standard. The one-stage and chromogenic assays quantified the FVIII
      levels. The TGA assay was activated using either FIXa or FXIa. RESULTS: Both FIXa
      and FXIa-activated TGA were sensitive across FVIII concentrations, with intra
      assay coefficient of variation (CV) < 10%. The FXIa-activated assay had 25% CV at
      the lowest level of FVIII compared to 10% CV with FIXa activation. There were
      strong correlations between the FIXa- and FXIa-activated TGA tests (R2  = 0.9912)
      and between the one-stage and chromogenic assays (R2  = 0.9469). However, there
      were poor relationships between the TGA tests and one-stage and chromogenic
      assays. CONCLUSIONS: Both FIXa- and FXIa activation results in similar TGA
      profiles across a FVIII range of 0.1%-33%; however, FIXa activation was more
      robust at the lowest levels of FVIII compared with FXIa activation.

PMID- 30112857
TI  - Competition of Candida glabrata against Lactobacillus is Hog1 dependent.
AB  - Candida glabrata is a common human fungal commensal and opportunistic pathogen.
      This fungus shows remarkable resilience as it can form recalcitrant biofilms on
      indwelling catheters, has intrinsic resistance against azole antifungals, and is
      causing vulvovaginal candidiasis. As a nosocomial pathogen, it can cause life
      threatening bloodstream infections in immune-compromised patients. Here, we
      investigate the potential role of the high osmolarity glycerol response (HOG) MAP
      kinase pathway for C. glabrata virulence. The C. glabrata MAP kinase CgHog1
      becomes activated by a variety of environmental stress conditions such as osmotic
      stress, low pH, and carboxylic acids and subsequently accumulates in the nucleus.
      We found that CgHog1 allows C. glabrata to persist within murine macrophages, but
      it is not required for systemic infection in a mouse model. C. glabrata and
      Lactobacilli co-colonise mucosal surfaces. Lactic acid at a concentration
      produced by vaginal Lactobacillus spp. causes CgHog1 phosphorylation and
      accumulation in the nucleus. In addition, CgHog1 enables C. glabrata to tolerate
      different Lactobacillus spp. and their metabolites when grown in co-culture.
      Using a phenotypic diverse set of clinical C. glabrata isolates, we find that the
      HOG pathway is likely the main quantitative determinant of lactic acid stress
      resistance. Taken together, our data indicate that CgHog1 has an important role
      in the confrontation of C. glabrata with the common vaginal flora.

PMID- 30112859
TI  - Hepatobiliary and Pancreatic: Mauriac syndrome: A rare cause of elevated liver
      enzymes.

PMID- 30112858
TI  - TP53 is not a prognostic marker-clinical consequences of a generally disregarded
      fact.
AB  - Technological progress within the last 15-20 years has significantly increased
      our knowledge about the molecular basis of cancer development, tumor progression,
      and treatment response. As a consequence, a vast number of biomarkers have been
      proposed, but only a small fraction of them have found their way into clinical
      use. The aim of this paper is to describe the specific demands a clinically
      relevant biomarker should meet and how biomarkers can be tested stepwise. We name
      this procedure the "triple-R principle": robustness, reproducibility, and
      relevance. The usefulness of this principle is illustrated with the marker TP53.
      Since it is mutated in a broad spectrum of cancer entities, TP53 can be
      considered a very promising marker. Thus, TP53 has been studied in detail but
      there is still no explicit consensus about its clinical value. By considering our
      own experience and reviewing the literature, we demonstrate that a major problem
      of current biomarker research is disregard of whether the biomarker is prognostic
      or predictive. As an example, it is demonstrated that TP53 is not a prognostic
      marker, but rather a purely predictive marker, and that disregard of this fact
      has made this otherwise strong biomarker appear as not being clinically useful so
      far.

PMID- 30112861
TI  - A severe chronic outdoor urban pollution alters some facial aging signs in
      Chinese women. A tale of two cities.
AB  - BACKGROUND: The impact of a chronic outdoor urban pollution on skin aging-related
      facial signs is a poorly referenced topic. OBJECTIVE: To assess, through visual
      grading and referential photographic atlas, possible differences in some facial
      signs between Chinese women, of comparable ages, living in two close cities very
      differently exposed to urban pollution. METHODS: The faces of two cohorts of 204
      Chinese women (2 * 102) of same age-groups (25-45 years), living in Baoding (a
      highly polluted city) and Dalian (a less polluted city), for at least 15 years,
      have been analyzed. Standardized facial photographs (full face and lateral views)
      were taken and examined, focusing on 26 signs that belong to 3 different clusters
      (wrinkles and skin texture, pigmentation disorders, and skin pores/skin redness).
      The severity of each facial sign was graded by 15 trained experts with the help
      of an Asian skin referential photographic Atlas that illustrates various scales
      of clinical severity (0-5, 0-8...). In addition, a naive panel of 80 Chinese non
      expert women was asked, while viewing all photographs, to answer to 4 questions
      regarding skin radiance, dullness, healthy appearance, and perceived age.
      RESULTS: The increased severity of almost all facial signs was mostly observed in
      the older group (40-45 years) living in Baoding. In particular, the clinical
      severity of eight facial signs (five related to skin structure and three related
      to pigmentation) was found strongly and significantly enhanced by a regular
      exposure to a severe chronic urban pollution. The naive panel judged the facial
      appearance of women from Baoding less radiant, duller, less healthy, and found
      them older than their Dalian counterparts. The monthly-recorded weather
      conditions (UV radiance, temperature, wind, precipitations) of the two cities (of
      same latitude) show that these only differ by their very different Air Quality
      Indexes (AQI). The daily life conditions of all women (UV exposure, use of
      cosmetic facial products, intake of sweet or spicy food...) were found similar in
      all age-groups. CONCLUSION: As compared to a moderately polluted region, a severe
      chronic outdoor urban pollution favors the aggravation of some facial signs in
      Chinese women. In short, a highly polluted environment can be viewed as an
      additional accelerating factor of the skin aging process, when compared to a
      moderately polluted area.

PMID- 30112860
TI  - Parallel domestication with a broad mutational spectrum of determinate stem
      growth habit in leguminous crops.
AB  - Stem growth habit is a key plant architecture trait determining yield potential
      in grain legumes, and the phenotypic change from the indeterminate stem growth
      habit of wild mungbeans (Vigna radiata) to the determinate stem growth habit of
      cultivated mungbeans is a critical domestication transition. Here we show that
      indeterminate stem growth in wild mungbean is modulated by a single gene, VrDet1,
      which encodes a signaling protein of shoot apical meristems. The transition from
      an indeterminate to a determinate stem growth habit was achieved by selection of
      two linked point mutations in two putative cis-regulatory elements, resulting in
      a significant reduction in gene expression. Both the wild-type nucleotides
      corresponding to the two point mutations were essential for VrDet1 function. In
      addition, two highly diverse haplotypes of Vrdet1 were found in cultivated
      mungbeans, suggesting dual domestication of Vrdet1. VrDet1 was orthologous to Dt1
      in wild soybean and PvTFL1y in wild common bean, where multiple loss-of-function
      mutations altering the coding sequences of individual genes were selected to
      produce determinate stems in cultivated accessions. Interspecific comparison of
      these orthologs in the wild and cultivated accessions reveals the most
      conservative interspecific and intraspecific parallel domestication events with
      the broadest mutational spectrum of a domestication trait in leguminous crops. We
      also found that interspecifically and functionally conserved promoters possess
      cis-regulatory elements that are highly conserved in kind but greatly variable in
      number and order, demonstrating the evolutionary dynamics of regulatory
      sequences. This work provides insights into the origins of cultivated mungbean
      and exemplifies the conservativeness and plasticity of the domestication
      processes of related crops.

PMID- 30112862
TI  - Association of Toll-like receptor 4 polymorphism with hepatitis E virus-infected
      Indian patients.
AB  - Hepatitis E infection caused by hepatitis E virus (HEV), a major public health
      concern in developing countries, is responsible for sporadic and epidemic acute
      viral hepatitis in adults. Pathogenesis of hepatitis E infection is poorly
      understood. Toll-like receptors (TLRs) are the key players of innate immunity
      recognize pathogen-associated molecular patterns (PAMPs). Previously, we found
      higher TLR4 expression (at protein and gene level) with impaired cytokine
      response upon stimulus of PBMCs with LPS in HEV-infected patients. In view of the
      earlier observations of the association of polymorphisms in TLR4 genes (A299G,
      C399T) with liver diseases, we investigated TLR4 polymorphisms in HEV-infected
      patients. We observed the significant association of TLR4-399CC and CT alleles
      with hepatitis E (both subclinical and acute patients). Carrier frequency of TLR4
      399 CT was lower in patients' categories in comparison with the controls. Higher
      frequency of allele TLR4-399C significantly correlated with disease progression.
      Acute hepatitis E patients showed the higher frequency of CG and TA haplotypes,
      while the rare haplotype (TG) was more frequent in controls. The other single
      nucleotide polymorphism (SNP) at TLR4-299 (A>G) did not show any difference. We
      report here for the first time the association of TLR4 polymorphism with
      hepatitis E and suggest that TLR 4 hyporesponsiveness during HEV infection might
      be related to its polymorphism.

PMID- 30112863
TI  - Rate and appropriateness of polypharmacy in older patients with hemophilia
      compared with age-matched controls.
AB  - BACKGROUND: In older people, multiple chronic ailments lead to the intake of
      multiple medications (polypharmacy) that carry a number of negative consequences
      (adverse events, prescription and intake errors, poor adherence, higher
      mortality). Because ageing patients with haemophilia (PWHs) may be particularly
      at risk due to their pre-existing multiple comorbidities (arthropathy, liver
      disease), we chose to analyse the pattern of chronic drug intake in a cohort of
      PWHs aged 60 years or more. PATIENTS AND METHODS: S + PHERA is a multicentre
      observational study, with the broad goal to evaluate prospectively the health
      status and medication intake in 102 older patients with severe haemophilia A or B
      compared with 204 age- and residence-matched controls chosen randomly from the
      same general practices of PWHs. The rate of potential drug-drug interactions
      (PDDI) was evaluated as a proxy of prescription appropriateness. RESULTS: After
      excluding replacement therapies and antiviral drugs, PWHs took in average less
      daily drugs than controls (2.4 +/- 2.5 vs 3.0 +/- 2.4) and had a lower rate of
      polypharmacy. Moreover, their prevalence of PDDI was lower (16.7% vs 27%).
      CONCLUSIONS: The rate of polypharmacy and the appropriateness of medications
      other than those for haemophilia and related comorbidities are acceptable in
      Italian PWHs, and better than those in their age peers without haemophilia,
      perhaps owing to drug tailoring and deprescribing by the specialized haemophilia
      centres at the time of regular visits. However, the PWHs investigated herewith
      were relatively young and the rate of polypharmacy and related PDDIs may become
      more prominent and crucial when older ages are reached, suggesting the need of
      continuous surveillance on prescribed drugs and the risk of drug-drug
      interactions.

PMID- 30112864
TI  - Respiratory motion estimation of the liver with abdominal motion as a surrogate.
AB  - BACKGROUND: Respiratory-induced motion (RIM) causes uncertainties in localizing
      hepatic lesions, which could lead to inaccurate targeting during interventions.
      One approach to mitigate the problem is respiratory motion estimation (RME), in
      which the liver motion is estimated by measuring external signals called
      surrogates. METHODS: A learning-based approach has been developed and validated
      to estimate the RIM of hepatic lesions. External markers placed on the human's
      abdomen were chosen as surrogates. Accordingly, appropriate motion models
      (multivariate, Ridge and Lasso regression models) were designed to correlate the
      liver motion with the abdominal motion, and trained to estimate the superior
      inferior (SI) motion of the liver. Three subjects volunteered for 6 sessions of
      such that liver images acquired by magnetic resonance imaging (MRI) were recorded
      alongside camera-tracked external markers. RESULTS AND CONCLUSIONS: The proposed
      machine learning approach was validated in MRI on human subjects and the results
      show that the approach could estimate the respiratory-induced SI motion of the
      liver with a mean absolute error (MAE) accuracy below 2 mm.

PMID- 30112865
TI  - Empirically derived dietary patterns and serum inflammatory markers in Iranian
      female teachers: A cross-sectional study.
AB  - AIM: To examine the relationship between dietary patterns and inflammatory
      markers including serum high sensitivity C-reactive protein (hs-CRP) and
      interleukin 17A (IL-17A) in females. METHODS: In the present cross-sectional
      study in female teachers living in Yazd, central Iran, data on anthropometric
      measurements and general information were gathered. A food frequency
      questionnaire was completed by participants and then, subjects were invited to
      give blood samples. Major dietary patterns were derived using principal component
      analysis and serum inflammatory markers were compared according to quintiles of
      dietary patterns scores. RESULTS: In total, 320 subjects aged 40.38 +/- 8.08
      years were included. Three dietary patterns were derived: (i) 'traditional' with
      a high intake of poultry, salt, eggs, other vegetables and red meat; (ii)
      'vegetables and fruits' with a higher intake of tomatoes, yoghurt drinks, green
      leafy vegetables, dried fruits, fruits, other vegetables and organ meats and
      (iii) 'dairy and saturated fat' with a high loading of high-fat dairy products,
      butter, low-fat dairy, margarine, eggs, other vegetables and green leafy
      vegetables. Participants in the highest quintile of the 'vegetables and fruits'
      dietary pattern had significantly lower serum hs-CRP levels compared to those in
      the lowest quintile (3.6 +/- 0.4 mg/L vs 2.6 +/- 0.4 mg/L, respectively; P <
      0.05). None of the dietary patterns were associated with circulating IL-17
      levels. CONCLUSIONS: Higher consumption of fruits and vegetables is inversely
      associated with serum hs-CRP but not IL-17 levels. Studies investigating the
      dietary patterns in association with IL-17 in other populations are recommended.

PMID- 30112866
TI  - Therapeutic Role of Yoga in Type 2 Diabetes.
AB  - Yoga originated in India more than 5,000 years ago and is a means of balancing
      and harmonizing the body, mind, and emotions. Yoga practice is useful in the
      management of various lifestyle diseases, including type 2 diabetes. Psycho-neuro
      endocrine and immune mechanisms are involved in the beneficial effects of yoga on
      diabetes. Incorporation of yoga practice in daily life helps to attain glycaemic
      control and reduces the risk of complications in people with diabetes. In this
      review, we briefly describe the role of various yoga practices in the management
      of diabetes based on evidence from various clinical studies.

PMID- 30112867
TI  - Factors Associated with Resolution of Hypertension after Adrenalectomy in
      Patients with Primary Aldosteronism.
AB  - BACKGROUND: The aim of this study was to investigate the factors associated with
      resolution of hypertension after adrenalectomy in patients with primary
      aldosteronism. A secondary aim was to describe our use of the contralateral ratio
      in adrenal venous sampling (AVS) in the setting of suboptimal successful
      cannulation rates. METHODS: A retrospective review of patients who underwent AVS
      followed by unilateral adrenalectomy for primary aldosteronism was performed.
      RESULTS: Complete resolution of hypertension and hypokalemia was seen in 17 of 40
      patients (42.5%), while a clinical improvement in hypertension was seen in 38 of
      40 (95%). Shorter duration of hypertension, mean aldosteronoma resolution score
      (ARS), and a high ARS of 3 to 5 were associated with resolution of hypertension
      after adrenalectomy (P=0.02, P=0.02, and P=0.004, respectively). Of the
      individual components of ARS, only a duration of hypertension of <=6 years was
      associated with resolution of hypertension after adrenalectomy (P=0.03).
      CONCLUSION: A shorter duration of hypertension was significantly associated with
      resolution of hypertension after adrenalectomy in patients with primary
      aldosteronism.

PMID- 30112868
TI  - An Ectopic Cortisol-Producing Adrenocortical Adenoma Masquerading as a
      Liposarcoma in the Pararenal Space.

PMID- 30112871
TI  - Corrigendum: Correction of Acknowledgments. Association between Serum Fibroblast
      Growth Factor 21 Levels and Bone Mineral Density in Postmenopausal Women.
AB  - This corrects the article on p. 273 in vol. 33, PMID: 29947182.

PMID- 30112870
TI  - Corrigendum: Author's Name Correction. Study Protocol of Multicenter Prospective
      Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma
      (MAeSTro).
AB  - This corrects the article on p. 278 in vol. 33, PMID: 29947183.

PMID- 30112872
TI  - Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in
      Patients with Acute Coronary Syndrome.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a
      circulating protein that promotes degradation of the low density lipoprotein
      receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the
      predictive value of the serum level of PCSK9 for the severity of coronary disease
      is largely unknown. METHODS: From December 2009 to July 2012, 121 individuals who
      underwent coronary angiography (CAG) because of clinically suspected acute
      coronary syndrome were enrolled in this study. Serum levels of PCSK9 and
      metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary
      intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE
      (Global Registry of Acute Coronary Events) scores were calculated. RESULTS:
      Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9
      than those without lesions (n=21). The study population was stratified into three
      groups according to serum levels of PCSK9. The odds radio for occurrence of one
      or more CAG lesions was significantly higher in the group with the highest level
      of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of
      PCSK9. Serum PCSK9 was positively associated with the number of involved coronary
      arteries. Multivariable linear regression indicated that levels of PCSK9 were
      positively correlated with GRACE risk scores and SYNTAX scores. CONCLUSION: Serum
      PCSK9 concentrations are higher in patients with coronary artery lesions, and are
      associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential
      biomarker of the severity of coronary artery disease.

PMID- 30112869
TI  - Regulation of Osteoblast Metabolism by Wnt Signaling.
AB  - Wnt/beta-catenin signaling plays a critical role in the achievement of peak bone
      mass, affecting the commitment of mesenchymal progenitors to the osteoblast
      lineage and the anabolic capacity of osteoblasts depositing bone matrix. Recent
      studies suggest that this evolutionarily-conserved, developmental pathway exerts
      its anabolic effects in part by coordinating osteoblast activity with
      intermediary metabolism. These findings are compatible with the cloning of the
      gene encoding the low-density lipoprotein related receptor-5 (LRP5) Wnt co
      receptor from a diabetes-susceptibility locus and the now well-established
      linkage between Wnt signaling and metabolism. In this article, we provide an
      overview of the role of Wnt signaling in whole-body metabolism and review the
      literature regarding the impact of Wnt signaling on the osteoblast's utilization
      of three different energy sources: fatty acids, glucose, and glutamine. Special
      attention is devoted to the net effect of nutrient utilization and the mode of
      regulation by Wnt signaling. Mechanistic studies indicate that the utilization of
      each substrate is governed by a unique mechanism of control with beta-catenin
      dependent signaling regulating fatty acid beta-oxidation, while glucose and
      glutamine utilization are beta-catenin-independent and downstream of mammalian
      target of rapamycin complex 2 (mTORC2) and mammalian target of rapamycin complex
      1 (mTORC1) activation, respectively. The emergence of these data has provided a
      new context for the mechanisms by which Wnt signaling influences bone
      development.

PMID- 30112873
TI  - Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal
      Tubulopathy in Subjects with Early Diabetic Kidney Disease.
AB  - BACKGROUND: The aim of this study was to investigate which glycemic parameters
      better reflect urinary N-acetyl-beta-D-glucosaminidase (uNAG) abnormality, a
      marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM)
      subjects with normoalbuminuria and a normal estimated glomerular filtration rate
      (eGFR). METHODS: We classified 1,061 participants with T2DM into two groups
      according to uNAG level-normal vs. high (>5.8 U/g creatinine)-and measured their
      biochemical parameters. RESULTS: Subjects with high uNAG level had significantly
      higher levels of fasting and stimulated glucose, glycated albumin (GA), and
      glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment
      of beta-cell compared with subjects with normal uNAG level. Multiple linear
      regression analyses showed that uNAG was significantly associated with GA
      (standardized beta coefficient [beta]=0.213, P=0.016), but not with HbA1c (beta=
      0.137, P=0.096) or stimulated glucose (beta=0.095, P=0.140) after adjusting
      confounding factors. In receiver operating characteristic analysis, the value of
      the area under the curve (AUC) for renal tubular injury of GA was significantly
      higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for
      HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI,
      0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The
      optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%,
      specificity 62%). CONCLUSION: GA is a more useful glycation index than HbA1c for
      reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and
      normal eGFR.

PMID- 30112874
TI  - Synthesis of a New Zinc-Mixed Ligand Complex and Evaluation of Its Antidiabetic
      Properties in High Fat Diet: Low Dose Streptozotocin Induced Diabetic Rats.
AB  - Due to the multifactorial and multisystemic nature of diabetes mellitus, it is
      often treated with a combination of therapeutic agents having different mode of
      action. Earlier, we have synthesized several organozinc complexes and evaluated
      their safety and antidiabetic properties in experimental type 2 diabetes mellitus
      (T2DM). More recently, we have synthesized a metformin-3-hydroxyflavone complex
      and studied its antidiabetic efficacy in experimental rats. In the present study,
      a new zinc-mixed ligand (metformin-3-hydroxyflavone) was synthesized,
      characterized by spectral studies and its antidiabetic properties was evaluated
      in HFD fed-low dose streptozotocin induced T2DM in rats. The hypoglycemic
      efficacy of the complex was evaluated through oral glucose tolerance test,
      homeostasis model assessment of insulin resistance, quantitative insulin
      sensitivity check index and by determining the status of important biochemical
      parameters. Oral administration of the complex at a concentration of 10 mg/kg
      body weight/rat/day for 30 days significantly improved the glucose homeostasis.
      The complex possesses significant antidiabetic properties relatively at a less
      concentration than metformin-3-hydroxyflavone complex in ameliorating
      hyperglycemia.

PMID- 30112875
TI  - Inhibition of Serotonin Synthesis Induces Negative Hepatic Lipid Balance.
AB  - BACKGROUND: Hepatic steatosis is caused by metabolic stress associated with a
      positive lipid balance, such as insulin resistance and obesity. Previously we
      have shown the anti-obesity effects of inhibiting serotonin synthesis, which
      eventually improved insulin sensitivity and hepatic steatosis. However, it is not
      clear whether serotonin has direct effect on hepatic lipid accumulation. Here, we
      showed the possibility of direct action of serotonin on hepatic steatosis.
      METHODS: Mice were treated with para-chlorophenylalanine (PCPA) or LP-533401 to
      inhibit serotonin synthesis and fed with high fat diet (HFD) or high carbohydrate
      diet (HCD) to induce hepatic steatosis. Hepatic triglyceride content and gene
      expression profiles were analyzed. RESULTS: Pharmacological and genetic
      inhibition of serotonin synthesis reduced HFD-induced hepatic lipid accumulation.
      Furthermore, short-term PCPA treatment prevented HCD-induced hepatic steatosis
      without affecting glucose tolerance and browning of subcutaneous adipose tissue.
      Gene expression analysis revealed that the expressions of genes involved in de
      novo lipogenesis and triacylglycerol synthesis were downregulated by short-term
      PCPA treatment as well as long-term PCPA treatment. CONCLUSION: Short-term
      inhibition of serotonin synthesis prevented hepatic lipid accumulation without
      affecting systemic insulin sensitivity and energy expenditure, suggesting the
      direct steatogenic effect of serotonin in liver.

PMID- 30112876
TI  - The Role of Advanced Glycation End Products in Diabetic Vascular Complications.
AB  - In cases of chronic hyperglycemia, advanced glycation end-products (AGEs) are
      actively produced and accumulated in the circulating blood and various tissues.
      AGEs also accelerate the expression of receptors for AGEs, and they play an
      important role in the development of diabetic vascular complications through
      various mechanisms. Active interventions for glucose and related risk factors may
      help improve the clinical course of patients by reducing AGEs. This review
      summarizes recent updates on AGEs that have a significant impact on diabetic
      vascular complications.

PMID- 30112878
TI  - Higher Prevalence and Progression Rate of Chronic Kidney Disease in Elderly
      Patients with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: To evaluate the prevalence of chronic kidney disease (CKD) and
      progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM).
      METHODS: We investigated the medical records of 190 elderly patients (65 years or
      older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration
      was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR)
      <60 mL/min/1.73 m2 and/or the presence of albuminuria. RESULTS: The mean age was
      70.4 years and mean diabetes duration was 10.6 years. Among all the participants,
      113 patients (59.5%) had CKD. The eGFR was significantly decreased between
      baseline (65.7+/-15.0 mL/min/1.73 m2) and the end of follow-up (52.7+/-17.5
      mL/min/1.73 m2, P<0.001). At the end of follow-up, the prevalence of eGFR <60
      mL/min/1.73 m2 had increased by 61.6% (at baseline, 44.2%). Furthermore, in
      patients with eGFR >=60 mL/min/1.73 m2, the progression rate to more than CKD
      stage 3 was 39.6% at the end of follow-up; 30.2% of elderly diabetic patients had
      progressed to albuminuria from normoalbuminuria. Kaplan-Meier analysis showed
      that the time interval to worsening nephropathy was significantly shorter in
      elderly patients with diabetes duration >=10 years than in those with diabetes
      duration <5 years (P=0.018). CONCLUSION: CKD was commonly observed in older
      patients with T2DM, and the progression rate to CKD is also high. Consequently,
      it is important to identify and manage CKD as early as possible in elderly
      patients with T2DM, especially in those with diabetes duration >=10 years.

PMID- 30112879
TI  - Predictors of Incident Type 2 Diabetes Mellitus in Japanese Americans with Normal
      Fasting Glucose Level.
AB  - BACKGROUND: Little is known about the natural course of normal fasting glucose
      (NFG) in Asians and the risk factors for future diabetes. METHODS: A total of 370
      Japanese Americans (163 men, 207 women) with NFG levels and no history of
      diabetes, aged 34 to 75 years, were enrolled. Oral glucose tolerance tests were
      performed at baseline, 2.5, 5, and 10 years after enrollment. RESULTS: During 10
      years of follow-up, 16.1% of participants met criteria for diabetes diagnosis,
      and 39.6% of subjects still had NFG levels at the time of diabetes diagnosis.
      During 5 years of follow-up, age (odds ratio [OR], 1.05; 95% confidence interval
      [CI], 1.01 to 1.10; P=0.026) and family history of diabetes (OR, 3.24; 95% CI,
      1.42 to 7.40; P=0.005) were independently associated with future diabetes
      diagnosis; however, fasting glucose level was not an independent predictor.
      During 10 years of follow-up, family history of diabetes (OR, 2.76; 95% CI, 1.37
      to 5.54; P=0.004), fasting insulin level (OR, 1.01; 95% CI, 1.00 to 1.02;
      P=0.037), and fasting glucose level (OR, 3.69; 95% CI, 1.13 to 12.01; P=0.030)
      were associated with diabetes diagnosis independent of conventional risk factors
      for diabetes. CONCLUSION: A substantial number of subjects with NFG at baseline
      still remained in the NFG range at the time of diabetes diagnosis. A family
      history of diabetes and fasting insulin and glucose levels were associated with
      diabetes diagnosis during 10 years of follow-up; however, fasting glucose level
      was not associated with diabetes risk within the relatively short-term follow-up
      period of 5 years in subjects with NFG.

PMID- 30112880
TI  - Bone morphogenetic proteins and inner ear development.
AB  - Bone morphogenetic proteins (BMPs) are the largest subfamily of the transforming
      growth factor-beta superfamily, and they play important roles in the development
      of numerous organs, including the inner ear. The inner ear is a relatively small
      organ but has a highly complex structure and is involved in both hearing and
      balance. Here, we discuss BMPs and BMP signaling pathways and then focus on the
      role of BMP signal pathway regulation in the development of the inner ear and the
      implications this has for the treatment of human hearing loss and balance
      dysfunction.

PMID- 30112881
TI  - Clinical lymphocytes construction for light scattering inversion study: a three
      dimensional morphology constructed method from defective confocal images.
AB  - Constructing models of cells' realistic internal and external morphology is vital
      for correlation between light scattering and morphology of the scattering
      structure. The image stack obtained from fluorescent confocal microscopy is at
      present used to construct the cell's three-dimensional (3-D) morphology. However,
      due to the poor labeling quality and unavoidable optical noise present in the
      image stacks, 3-D morphologies are difficult to construct and are an impediment
      to the statistical analyses of cell structures. We propose a method called the
      "area and shape constraint method (ASCM)" for constructing 3-D morphology.
      Blurred 3-D morphologies constructed by common methods from image stacks
      considered as defective and which are commonly discarded are well restored by the
      ASCM. Seventy-four clinical blood samples and a series of standard fluorescent
      spheres are selected to evaluate the validity and precision of our proposed ASCM.
      Both the qualitative and quantitative results obtained by ASCM indicate the good
      performance of the method in constructing the cell's 3-D morphology.

PMID- 30112882
TI  - [Design of Intelligent Nursing Bed Based on Internet of Things + Technology].
AB  - With the advent of social aging, the development of intelligent multifunctional
      nursing beds that are suitable for hospitals, nursing homes, homes and the like
      has a wide range of applications, this paper presents an intelligent nursing bed
      design based on Internet of Things technology. The design uses STM32F103 as the
      central processor. The design is divided into nursing bed module based on tri
      fold structure, central control module based on data processing, weight scale
      module based on weight detection, power supply module based on system power
      supply and host computer module based on user operation. The design uses a closed
      control mode, greatly improving the bed control accuracy. Experimental tests
      showed that under the action of the intelligent control bed control system, the
      error rate of bed position information driven bedboard can be less than 2%, which
      has high accuracy and stability.

PMID- 30112883
TI  - [Failure Analysis of Metal Bone Plate].
AB  - The internal fixation using metal bone plate is one of common method for the
      clinical treatment of fracture, it plays a role in fixation, protection and
      supporting of the fractured bone segments, but it also suffers high failure rates
      in clinical practice. This article reviewed the commonly used methods of failure
      analysis of bone plate, and described the research results of the failure
      analysis of bone plate in detail. The fatigue fracture of bone plate caused by
      stress concentration is the common fracture pattern. In addition, the article
      summarized the performance optimizations according to the cause of failure, then
      discussed its future development trends.

PMID- 30112884
TI  - [Study on the Migration Resistance of Additives in Disposable Photophobic
      Infusion Set].
AB  - The disposable photophobic infusion was used to simulate clinical infusion under
      different conditions. The simulated liquid was collected every 30 min (total 4
      h),and detected the additives (Fe3+, MDA and antioxidant 1076) in simulated
      liquid by spectroscopic method and chromatography method. The method is simple
      and stable, and can be used for the technical monitoring of the disposable
      photophobic infusion set in the future.

PMID- 30112885
TI  - [Research on Chemical Equivalence Characteristics of Polylactic Acid in Medical
      Devices].
AB  - Polylactic acid is synthesized indirectly by the polymerization method, according
      to the standard GB/T 16886.18-2011, the evaluation parameters and methods about
      chemical characterization of polylactic acid have been established. By using
      rigorous and comprehensive comparative analysis, the chemical equivalency of
      domestic and imported polylactic acid materials has been proved, along with the
      "Medical Device Biology Evaluation and Review Guide", paving the way of using
      domestic polylactic acid in implantable medical devices.

PMID- 30112887
TI  - [Design of ECG Monitoring Analyzer Based on MicrocontrollerCC2530].
AB  - OBJECTIVE: A remote wireless electrocardiogram (ECG) monitoring system is
      designed by using the CC2530 micro-controller as the device core. METHODS:
      Acquisition, conversion and data processing for ECG signals are realized on
      CC2530 micro-controllers. And the ECG data is transmitted to the coordinator by
      using ZigBee. It realizes the real-time monitoring of ECG signals and heart rate
      variability (HRV) data. RESULTS: The test results show that the maximum error of
      the designed ECG monitoring analyzer is 3 beats per minute and the average error
      is 1.6 beats per minute, which can meet the requirement of pharmaceutical
      industry standards of the People's Republic of China. CONCLUSIONS: The ECG
      monitoring analyzer has good portability, high measurement precision and good
      practical application values.

PMID- 30112886
TI  - [Design of Magnetic Clutch System for Electromagnetic Control Laparoscopic
      Surgery Based on Magnetic Anchoring System].
AB  - Magnetic anchor technique can reduce the number of trocar in laparoscopic
      surgery. The laparoscopic magnetic anchor system consists of an external anchor
      magnet and the magnetic clutch system. Electromagnetic control laparoscopic
      surgery clutch system includes the internal grasper and the operating forceps. In
      this design, a permanent magnet is set at the tail of the internal grasper, and
      an electromagnetic device is installed at the head of the operating forceps. The
      magnetic field direction of the electromagnetic device can be changed by
      switching the positive pole and the negative pole of the electromagnetic device,
      so as to control the separation and combination of the operating forceps and the
      internal grasper. The design of this system is ingenious, easy to manufacture and
      the operation is simple.

PMID- 30112888
TI  - [Hardware System for the Test of Artificial Joint Biomechanics].
AB  - In the research of artificial joint biomechanics, it is a common method in the
      world to evaluate the biomechanical properties of the implanted fixtures through
      experiments in vitro. The domestic research started late, and the corresponding
      testing methods were lacking. There is still no unified standard. In this paper,
      a complete hardware test system was designed and built around the existing
      mechanical testing machine, including:binocular vision catcher, torque bearing
      clamp, film pressure sensor and so on. The system can accurately measure the
      relative motion angle value, external torque value, and inter pressure value of
      each joint. It has some reference significance for the forming and
      standardization of the artificial joints' evaluation system.

PMID- 30112889
TI  - [System Integration of Infant Incubators' Quality Control Testing Based on MCU].
AB  - This study is aimed to design the testing system of multiple parameters of the
      incubators, and to make their quality control plans. Also it is required to
      establish a model of data collection and processing based on MCU, and to program
      the host computer software in order to analyze data. The result shows that the
      testing system is accurate and stable; also it is convenient to collect the data.
      This testing system is a good complement of the quality control of incubators. It
      has a high practical value in improving medical safety and reducing the
      occurrence of adverse events.

PMID- 30112890
TI  - [Discussion on Clinical Trial Design of Artificial Hip Prosthesis].
AB  - Recently, the registration of artificial hip prosthesis products increased year
      by year. In the new version of the provisions for medical device registration,
      the domestic or import of such products in the registration declaration may need
      to complete a clinical trial in the country. How to carry out scientific clinical
      trials of the product design is the common concern of enterprises and clinical
      trial institutions. To review the guideline and literature concerning
      registration for artificial hip prosthesis, the focus on clinical trial design of
      artificial hip prosthesis include clinical inclusion, evaluation standard, sample
      size. Through the discussion, we hope to provide advice and guidance for clinical
      trials of this kind of products.

PMID- 30112891
TI  - [A Torso Simulator Design for Implantable Nerve Stimulator Test].
AB  - This paper introduces ISO 14708-3:2017, the new edition of the international
      standard for implantable neurostimulator, and emphasizes the new requirements in
      the clause of protection from RF electromagnetic interference. To meet this new
      requirements, this paper presents a design of torso simulator for the testing of
      implantable neurostimulator. The design includes volume conductor, electrodes and
      grids, which can simulate the actual operating environment of implantable
      neurostimulator in RF electromagnetic interference testing. The torso simulator
      is verified by performance in the last part of the paper.

PMID- 30112893
TI  - [Advances in Implantable Medical Device Battery].
AB  - In recent years, active implantable medical devices become a hot spot of the
      medical device industry. There are still many problems in terms of reliability,
      capacity and life expectancy because of the subject to material and technical
      constraints. This review summarizes the development history and current status of
      the batteries used in active implantable medical devices, and describes the
      development and problems of zinc-mercury batteries and lithium batteries. The
      flexible batteries and bio-energy battery and other new battery technology are
      also expounded. The future of active implanted medical device battery is bound to
      miniaturization, flexibility, rechargeable direction.

PMID- 30112892
TI  - [Development of Cardiac Output Monitoring Technology].
AB  - Cardiovascular disease has become a serious disease that threatens the health of
      human beings, cardiac output is an important indicator of cardiovascular
      function, monitoring cardiac output and related hemodynamic parameters have
      significant clinical value. This article summarizes the development history,
      principle, method, advantages and disadvantages of various monitoring
      technologies from three aspects:invasive, minimally invasive and noninvasive, the
      development and application of cardiac output monitoring technology are
      prospected.

PMID- 30112894
TI  - [Discussion on Quality Management System Construction for Evaluation of Medical
      Devices].
AB  - The quality management system is of great significance for improving efficiency
      and promoting sustainable development. This article introduces and discusses the
      related definitions, construction principles, improvements of document control
      and measurement analysis, and system construction, etc. of quality management
      system for evaluation of medical devices in order to provide references for
      relevant researchers.

PMID- 30112895
TI  - [Analysis of Technical Evaluation for Current Regulation of 3D Printed Customized
      Medical Device].
AB  - This paper summarizes the current research status of 3D printed customized
      medical devices regulations in US and EU. Based on the discussion of 3D printed
      customized medical devices in the US and the European Union, some thoughts are
      put forward from design, manufacturing, testing and other aspects.

PMID- 30112896
TI  - [How to Integrate GLP into Quality Management of Biological Tests of Medical
      Devices].
AB  - Biological tests of medical devices is an important part to evaluate its
      biological safety. Good quality management of the test is a powerful guarantee to
      ensure the authenticity, integrity and reliability of the test results. This
      paper is based on the biological tests of medical devices, compares GLP and
      ISO/IEC 17025 which is widely used in China medical device testing institutions,
      describes the implementation of the GLP reference points to strengthen the
      quality management of biological tests of medical devices under the ISO/IEC 17025
      system, to provide reference for quality management of medical device testing
      institutions.

PMID- 30112897
TI  - [Research and Reflection on Reprocessed Medical Devices Supervision].
AB  - Under the precondition of ensuring safety and effectiveness, whether to reuse
      reprocessed medical devices to reduce the medical expenses has become the focus
      of the relevant regulatory authorities in our country. In this paper, we studied
      the regulatory policy for reprocessed medical devices in major international
      economies, such as United States, Japan, European Union and so on. From the
      regulatory and technical level, we thought about the risks of supervising
      reprocessed medical devices, and analyzed the ideas and risk concerns of
      supervising reprocessed medical devices to provide reference for regulation of
      such devices in our country.

PMID- 30112898
TI  - [Cell Count of Mouse Blastocyst on Pre-clinical Evaluation of Safety of Medical
      Devices in Assisted Reproductive Technologies].
AB  - Various types of medical devices used in assisted reproductive technologies (ART)
      should be detected for their safety by strict biological assays. Mouse embryo
      assay(MEA)has been recognized as one of the most important and standardized
      methods with the threshold more than 80% of blastocyst formation rate (BR) after
      96 h culture of fertilized eggs. The disadvantage using BR for embryonic quality
      control has been concerned as it is ubiquitously dependent of embryonic
      morphology and the detailed data including molecular and genetic information is
      obviously missing and incomplete. This leads to the urgent requirement for more
      sensitive and efficient assessments for the quality control of ART. This study
      evaluated the reliability of an immunofluorescent MEA by counting total cell and
      differential number of the cells in the inner cell mass (ICM) and trophectoderm
      (TE) in the blastocyst. This method improved the traditional MEA, provided a
      sensitive and powerful platform to assess embryonic developmental viability and
      should be suggested as a standard assay to be globally used for the quality
      control of medical devices and pre-clinical procedures in ART.

PMID- 30112899
TI  - [Application and Safety Evaluation of DEHP in PVC Medical Devices].
AB  - DEHP is largely used in soft PVC products as the plasticizer, which is also
      widely applied in medical devices. Due to its potential and widespread toxicity
      and medical devices' specific use, the safety of DEHP's application in medical
      devices has received extensive attention. In this paper, a comprehensive review
      of the application and potential toxicity of DEHP in PVC medical devices is made
      on the basis of the research results all over the world. Besides, the safety
      evaluation in medical devices is discussed and some possible coping strategies
      are explored.

PMID- 30112900
TI  - [Research on Evaluating Method of Location of Dyeing Materials for Color Contact
      Lenses].
AB  - Combining frozen section and scanning electron microscopy experiments to observe
      the cross section and surface state of the samples, this study finds an effective
      method to evaluate the location of dyeing materials of color contact lenses.
      Sixty samples were evaluated on their dyeing location statistically using this
      method. The results showed that there were only 7 lots of samples with their
      dyeing materials within their product. This method is effective in evaluating the
      location of dyeing materials for color contact lenses.

PMID- 30112901
TI  - [Application of UDI in Quality Management of Laparoscopic Instruments].
AB  - Laparoscopic surgical instruments are expensive and have complex structures, the
      management is always huge challenge for managers. This paper introduces the basic
      concepts of UDI, Dot Pin Marking engraving in DPM technology and the practical
      solution to the case of laparoscopic instrument management. This paper summaries
      the application of UDI in the application of laparoscopic instruments and the
      prospect of future use.

PMID- 30112902
TI  - [Hospital Networked Medical Equipment Safety Management].
AB  - With the continuous improvement and wide application of hospital information,
      more and more medical equipment is integrated into the hospital information
      systems, which brings new work contents and challenges for the traditional
      clinical engineers. This paper reviews and evaluates the current situation of
      networked medical equipment in the hospital. By applying the ISO 80001 and the
      MDS2(Manufacturer Disclosore Statement for Medical Device Security), the paper
      puts forward the measures and suggestions for the security management of
      networked medical equipment.

PMID- 30112903
TI  - [Practice of Medical Device Clinical Evaluation].
AB  - For medical device clinical evaluation activities, reference to international and
      domestic medical device regulations and guidance documents, this paper briefly
      introduces the implementation steps of clinical evaluation of medical devices,
      and focus on the evaluation report should be included in the content, provides
      reference for relevant personnel of medical devices registration and
      certification on medical device clinical evaluation practice.

PMID- 30112904
TI  - [The Whole Life Cycle Information Management of Medical Equipment Based on HRP
      System].
AB  - Starting from the research on the whole life cycle management of medical
      equipment, based on the development and application of HRP management system,
      according to the characteristics of medical device management, this paper studies
      the specific implementation method of medical device life cycle management based
      on HRP system. Then, it provides an asset management solution of decision,
      management and operation for the decision, management and executive layer of the
      hospital.

PMID- 30112905
TI  - Rise of Conjugated Poly-ynes and Poly(Metalla-ynes): From Design Through
      Synthesis to Structure-Property Relationships and Applications.
AB  - Conjugated poly-ynes and poly(metalla-ynes) constitute an important class of new
      materials with potential application in various domains of science. The key
      factors responsible for the diverse usage of these materials is their intriguing
      and tunable chemical and photophysical properties. This review highlights
      fascinating advances made in the field of conjugated organic poly-ynes and
      poly(metalla-ynes) incorporating group 4-11 metals. This includes several
      important aspects of conjugated poly-ynes viz. synthetic protocols, bonding,
      electronic structure, nature of luminescence, structure-property relationships,
      diverse applications, and concluding remarks. Furthermore, we delineated the
      future directions and challenges in this particular area of research.

PMID- 30112906
TI  - Polymers with a Coiled Conformation Enable Healing of Wide and Deep Damages in
      Polymeric Films.
AB  - The development of efficient methods to trigger high mobility of polymer chains
      to migrate across the damaged areas is key for healing wide damages in intrinsic
      healable polymeric films deposited on solid substrates. Herein, we establish a
      facile strategy for the fabrication of polymeric films with a superhigh healing
      capability by controlling the conformational transition of the polymer chains in
      polymeric films. The alternately spin-coated poly(acrylic acid)
      (PAA)/polyurethane (PU) films with coiled PU can heal cuts with a width of 6
      times the thickness of the PAA/PU films in the presence of ethanol. In contrast,
      the same PAA/PU films with stretched PU or those films with coiled PU but without
      conformational transition from a coiled state to a stretched state fail to heal
      cuts. The conformational transition of PU from a coiled state to a stretched
      state in PAA/PU films triggered by ethanol enables a long-distance migration of
      PAA and PU polymers to heal wide mechanical damages.

PMID- 30112907
TI  - Spectroscopic and Electrochemical Properties of Electronically Modified
      Cycloplatinated Formazanate Complexes.
AB  - Formazanates are a class of monoanionic, chromophoric, redox-active chelating
      ligands, and until recently, the coordination chemistry of formazanates with
      third-row transition metals was unexplored. Described here is a series of
      heteroleptic cyclometalated platinum formazanate complexes of the type
      Pt(C^N)(Fz), where "C^N" is the cyclometalating ligand and "Fz" is the
      formazanate. This work includes a set of 14 complexes derived from four different
      cyclometalating ligands and five different formazans, greatly expanding the
      structural and electronic diversity of this class of complexes. The formazans
      fall into two major categories: triarylformazans with either electron-donating
      (Me, OMe) or electron-withdrawing (CN) para substituents, and even more electron
      deficient diarylformazans where the center position of the backbone is a cyano
      group. Seven of the new compounds are characterized by single-crystal X-ray
      diffraction, and all are characterized by cyclic voltammetry and UV-vis
      absorption spectroscopy to provide insight into the frontier orbitals. The
      complexes can be electrochemically reduced by three electrons, with the first two
      electrons populating formazanate-centered frontier orbitals and the third being
      added to the Pt-C^N fragment. The formazanate-based reduction potentials are
      highly sensitive to the substitution pattern of the formazanate and can be tuned
      over a wide range of ca. 0.8 V by altering substituents. The formazanates also
      impart these complexes with very strong, low-energy visible absorption bands
      assigned to HOMO -> LUMO transitions, which are greatly perturbed from the free
      ligand due to interactions of the formazanate frontier orbitals with platinum
      centered orbitals. Unlike the redox properties, the formazanate-derived visible
      absorption band is relatively insensitive to substituent effects. Additional
      visible absorption bands, attributed to Pt(d) -> C^N(pi*) MLCT transitions, can
      be tuned over a wide range by changing the structure of the C^N ligand, giving
      rise to strong panchromatic absorption for some members of the series.

PMID- 30112908
TI  - Lead Halide Perovskite Nanostructures for Dynamic Color Display.
AB  - Nanoprint-based color display using either extrinsic structural colors or
      intrinsic emission colors is a rapidly emerging research field for high-density
      information storage. Nevertheless, advanced applications, e. g., dynamic full
      color display and secure information encryption, call for demanding requirements
      on in situ color change, nonvacuum operation, prompt response, and favorable
      reusability. By transplanting the concept of electrical/chemical doping in the
      semiconductor industry, we demonstrate an in situ reversible color nanoprinting
      paradigm via photon doping, triggered by the interplay of structural colors and
      photon emission of lead halide perovskite gratings. It solves the aforementioned
      challenges at one go. By controlling the pumping light, the synergy between
      interlaced mechanisms enables color tuning over a large range with a transition
      time on the nanosecond scale in a nonvacuum environment. Our design presents a
      promising realization of in situ dynamic color nanoprinting and will empower the
      advances in structural color and classified nanoprinting.

PMID- 30112909
TI  - Umpolung Synthesis of Vicinal Diamines: Diastereoselective Addition of 2-Azaallyl
      Anions to Davis-Ellman's Imines.
AB  - A highly regioselective and diastereoselective addition of 2-azaallyl anions to N
      tert-butanesulfinylimines is reported. This methodology affords the preparation
      of enantiomerically and diastereomerically pure vicinal diamines bearing two
      adjacent stereocenters. Reactions proceed efficiently (yield up to 94%),
      diastereoselectively ( dr values up to 98:2:0:0), and site-selectively to deliver
      products with differentiated amino groups.

PMID- 30112910
TI  - Fully Functionalizable beta,beta'-BODIPY Dimer: Synthesis, Structure, and
      Photophysical Signatures.
AB  - The versatility in the synthesis of BODIPY derivatives in terms of
      functionalization is further demonstrated. In particular, in this work beta-beta'
      BODIPY dimers with varied functional groups in the meso positions were
      synthesized in very efficient yields and short reaction times from a single
      platform. A photophysical study was carried out in all of the compounds. The
      resultant dimers show absorption bands at around 600 nm as a consequence of
      electronically coupled monomers disposed with a dihedral angle of around 30
      degrees , which is supported by theoretical simulations. The emission properties
      of these molecules are distinguished by the appearance of an ICT state as the
      polarity of the solvent increases.

PMID- 30112911
TI  - Visible-Light-Triggered C-C and C-N Bond Formation by C-S Bond Cleavage of
      Benzylic Thioethers.
AB  - The cleavage of sulfidic C-S bonds under visible-light irradiation was harnessed
      to generate carbocations under neutral conditions and synthesize valuable di- and
      triarylalkanes as well as benzyl amines. To this end, photoredox catalysis and
      direct photoinduced C-S bond cleavage are used as complementary approaches and
      participate in the versatility of the general strategy. Extensive mechanistic
      studies have demonstrated the diversity of the reaction mechanism at work in
      these different reactions.

PMID- 30112913
TI  - Resilience strategies of HIV-positive parents who live with children within the
      family context in Bangladesh.
AB  - We have limited knowledge about the vulnerabilities faced by HIV-positive parents
      in families and the strategies they use to manage these circumstances in
      Bangladesh. A qualitative research design was used to analyse in-depth interviews
      with 19 HIV-positive parents who lived with their children in Khulna and Dhaka,
      Bangladesh. The findings indicate that resilience of HIV-positive parents was
      fostered through interaction with informal and formal social networks. The
      findings of this study demonstrate that social support groups can play a crucial
      role to construct new ways of coping and reintegrate HIV people into their
      families and society.

PMID- 30112912
TI  - Measuring the service system impact of a novel telediagnostic service program for
      young children with autism spectrum disorder.
AB  - As prevalence of autism spectrum disorder continues to increase, so too does the
      need for timely, accessible diagnostic consultation. The present work extends
      from a previous study which provided preliminary evidence for the feasibility of
      expert clinicians to utilize telemedicine to triage autism spectrum disorder risk
      in young children. However, it did not examine whether a telediagnostic model had
      a demonstrable impact on tertiary care center referrals and usage. We therefore
      examined whether the introduction of telemedicine-based diagnostic consultation
      for families served by a rural medical facility affected referrals overall as
      well as to a metropolitan tertiary care diagnostic center. Results suggest that
      telemedicine diagnostic consultation in partnership with a referring early
      intervention system may positively impact referrals for diagnostic evaluation as
      well as the ability of families to schedule and attend appointments.

PMID- 30112914
TI  - Transtheoretical model for change in obese adolescents: MERC randomized clinical
      trial.
AB  - The randomized controlled trial evaluated the effectiveness of an intervention
      based on the Transtheoretical Model of Change on anthropometric, metabolic and
      motivational outcomes in obese adolescents. A total of 135 male and female
      adolescents were randomized to two groups: intervention group ( n = 65) and
      control group ( n = 70). The adolescents were evaluated 1 week before the
      interventions began and at the end of 12 weeks. There was no statistically
      significant difference between groups in the outcome variables. Intervention
      group reported magnitude of effect more expressive on body mass index percentile,
      waist circumference, waist-to-hip ratio, readiness to change diet and readiness
      to start exercise.

PMID- 30112915
TI  - Racial-ethnic and neighborhood inequities in age of treatment receipt among a
      national sample of children with autism spectrum disorder.
AB  - The aim of this study is to examine the impact of child race-ethnicity and
      neighborhood characteristics on age of treatment receipt among children with
      autism spectrum disorder. Here, we included 1309 children diagnosed with autism
      spectrum disorder in the National Survey of Children's Health, 2011-2012.
      Controlling for key covariates, we used a weighted generalized logit model to
      analyze differences in age of treatment receipt (<2 years, 2 years, 3 years, and
      ?4 years). Compared to non-Hispanic White children, the relative probability
      (odds) of entering treatment at 3 years and ?4 years rather than <2 years was
      326% and 367% higher, respectively, for non-Hispanic Black children. Compared to
      children whose parents perceived their neighborhood to be cohesive, the relative
      probability of entering treatment at 2 years and 3 years rather than <2 years was
      59% and 61% lower, respectively, for children whose parents did not. Significant
      racial-ethnic and neighborhood inequities exist in age of treatment receipt,
      suggesting a need for research that explores the underlying causal mechanisms of
      inequities.

PMID- 30112916
TI  - Closing the Loop: Assuring That Skin Biopsy Results Are Received by Patients
      Following Hospital Discharge.

PMID- 30112917
TI  - Spray-dried fucoidan microparticles for pulmonary delivery of antitubercular
      drugs.
AB  - Pulmonary tuberculosis accounts for 80% of cases and the delivery of
      antitubercular drugs into the lungs allows targeting the infected organ and,
      possibly, reducing systemic drug toxicity. This work aimed at using fucoidan as
      matrix of inhalable microparticles that associate two first-line antitubercular
      drugs, for an application in pulmonary tuberculosis therapy. Fucoidan is composed
      of fucose and sulphated sugar residues, moieties described as being recognised by
      surface receptors of alveolar macrophages, which host mycobacteria. Inhalable
      fucoidan microparticles loaded with antitubercular drugs were successfully
      produced with high association efficiencies of either isoniazid (95%) or
      rifabutin (81%). The microparticles evidenced no cytotoxicity on lung epithelial
      cells (A549). However, rifabutin-loaded microparticles showed a certain degree of
      toxicity on macrophage-like cells (THP-1) at the highest tested concentration (1
      mg/mL). Furthermore, microparticles showed favourable aerodynamic properties for
      deep lung delivery (MMAD 2.0-3.8 um) and, thus, show potential for an application
      as inhalable tuberculosis therapy.

PMID- 30112918
TI  - Prognosis of Chronic Rhinosinusitis With Nasal Polyps Using Preoperative
      Eosinophil/Basophil Levels and Treatment Compliance.
AB  - Background Patients with chronic rhinosinusitis with nasal polyps (CRSwNP) have a
      high risk of disease recurrence and revision surgery. The ability to predict a
      polyp recurrence in this patient population is critical in order to provide
      adequately tailored postoperative management. Objective We aim to explore the
      role of appropriate postoperative care in the prognosis of CRSwNP patients in
      relation to preoperative eosinophil and basophils levels. Methods This was a
      retrospective case series; data were collected for 102 CRSwNP patients over a
      period of 15 months after surgery. Baseline eosinophil and basophil levels were
      compared between patients with and without polyp recurrences. The analysis was
      then stratified based on clinical diagnosis, comorbidities (atopy, asthma, and
      aspirin allergy), a single versus multiple episodes of sinonasal polyp
      recurrences, and medication adherence. Results Of the 102 included patients, 65
      (63.7%) of the patients experienced no recurrences, 26 (25.5%) experienced a
      single episode of recurrence, and 11 (10.8%) experienced multiple recurrences.
      Mean baseline eosinophil count and percentage of total white blood cells were
      significantly higher in the multiple recurrences group (0.70 * 109/L and 10%)
      compared with the no recurrences group (0.36 * 109/L and 5%). Adherence to
      prescribed medical therapy prior to the first episode of recurrence was
      significantly lower for the single exacerbations group (42.3%) than the multiple
      recurrences group (88.9%). Conclusions Patients with multiple recurrences of
      nasal polyps had significantly higher baseline eosinophil counts and
      significantly higher medication adherence compared to single exacerbations of
      nasal polyps. Single exacerbations may not reflect true failures of surgery but
      rather a failure of postoperative medical care. Basophil levels were inadequate
      to predict polyp recurrence rates.

PMID- 30112919
TI  - Sodium tanshinone IIA sulfate protects myocardium against paraquat-induced
      toxicity through activating the Nrf2 signaling pathway in rats.
AB  - OBJECTIVE: To investigate the therapeutic effect and mechanism of sodium
      tanshinone IIA sulfate (STS) on paraquat (PQ)-induced myocardial injuries in a
      rat model. METHODS: Healthy adult Sprague Dawley rats were randomly divided into
      normal control, PQ, and PQ + STS groups. PQ group was given a single intragastric
      administration of PQ (80 mg/kg). PQ + STS group was intraperitoneally injected
      with STS (1 ml/kg) at 30 min following PQ exposure. Rats in control and PQ groups
      were injected with equal amount of saline. After 12, 24, 48, and 72 h, rats were
      killed, and the apoptosis of myocardial cells was detected. Myocardial expression
      of Bax and Bcl-2 was measured. The activity of the nuclear erythroid 2-related
      factor 2 (Nrf2) pathway was assessed by Western blot. RESULTS: The apoptotic
      cells in PQ group were significantly increased in a time-dependent manner
      compared with the control group ( p < 0.01). The rats in PQ group exhibited
      significantly lower Bcl-2 expression, but notably higher Bax expression at 12,
      24, 48, and 72 h after PQ exposure ( p < 0.05 or 0.01). STS intervention markedly
      reduced the proportion of apoptotic myocardial cells, increased Bcl-2 expression,
      and decreased Bax expression at 24, 48, and 72 h after treatment ( p < 0.05 or
      0.01). The expression of phosphorylated Nrf2 and heme oxygenase 1 in PQ + STS
      group was significantly increased compared with PQ and control groups ( p < 0.05
      or 0.01). CONCLUSION: STS effectively inhibits PQ-induced myocardial cell
      apoptosis in rats via modulating the Nrf2 pathway, suggesting its potential as a
      promising therapeutic agent for PQ-induced myocardium damage.

PMID- 30112920
TI  - Sex-specific differences in the regulation of inducible nitric oxide synthase by
      bisphenol A in neutrophils.
AB  - The aim of the study was to evaluate the effect of bisphenol A (BPA) on nitric
      oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by
      neutrophils with regard to sex and nuclear factor-kappaB (NF-kappaB) pathway
      participation in this process. This study demonstrated that BPA intensifies the
      production of NO and the expression of iNOS in the cytoplasmic fraction of
      neutrophils of women as well as men. In addition, an enhanced expression of NF
      kappaB in the cytoplasmic and nuclear fraction of neutrophils exposed to BPA was
      observed in the cells of both sexes. The lipopolysaccharide (LPS) stimulation of
      neutrophils of both sexes led to an intensification of NO production and
      expression of all tested proteins. However, simultaneous stimulation of
      neutrophils of both men and women with LPS and BPA decreased the production of NO
      and expression of iNOS and NF-kappaB in both fractions compared to the cells
      exposed only to xenoestrogen. Moreover, expression of iNOS and NF-kappaB was
      higher in female neutrophils than in male cells. This study demonstrated that BPA
      affects the production of NO with the participation of iNOS by human
      polymorphonuclear neutrophils. This process is associated with the activation of
      the NF-kappaB pathway. In addition, different activity of NF-kappaB in
      neutrophils, observed with respect to sex, indicates a different role of this
      pathway in female and male cells.

PMID- 30112921
TI  - Early Postoperative Improvement in Sleep and Pain After Carpal Tunnel Release.
AB  - BACKGROUND: Carpal tunnel syndrome (CTS) is the most common compressive
      neuropathy of the upper extremity. We sought to assess the subjective improvement
      in preoperative symptoms related to CTS, particularly those affecting sleep, and
      describe opioid consumption postoperatively. METHODS: All patients undergoing
      primary carpal tunnel release (CTR) for electromyographically proven CTS were
      studied prospectively. All procedures were performed by hand surgery fellowship
      trained adult orthopedic and plastic surgeons in the outpatient setting. Patients
      underwent either endoscopic or open CTR from June 2017 to December 2017. Outcomes
      assessed were pre- and postoperative Quick Disabilities of Arm, Shoulder and Hand
      (QuickDASH), visual analog scale (VAS), and Pittsburgh Sleep Quality Index (PSQI)
      scores as well as postoperative pain control. RESULTS: Sixty-one patients were
      enrolled. At 2 weeks, all showed significant ( P < .05) improvement in QuickDASH
      scores. At 6 weeks, 40 patients were available for follow-up. When compared with
      preoperative scores, QuickDASH (51 vs 24.5; P < .05), VAS (6.7 vs 2.9; P < .05),
      and PSQI (10.4 vs 6.4; P < .05) scores continued to improve when compared with
      preoperative scores. At 2-week follow-up, 39 patients responded to the question,
      "How soon after your carpal tunnel surgery did you notice an improvement in your
      sleep?" Seventeen patients (43.6%) reported they had improvement in sleep within
      24 hours, 12 patients (30.8%) reported improvement between 2 and 3 days
      postoperatively, 8 patients (20.5%) reported improvement between 4 and 5 days
      postoperatively, and 2 patients (5.1%) reported improvement between 6 and 7 days
      postoperatively. CONCLUSIONS: The present study demonstrates rapid and sustained
      improvement in sleep quality and function following CTR.

PMID- 30112923
TI  - Effect of Endoscopic Sinus Surgery on Bronchiectasis Patients With Chronic
      Rhinosinusitis.
AB  - Background The concept of unified airway disease has linked bronchiectasis with
      chronic rhinosinusitis (CRS), much in the same way as in asthma and CRS. Although
      the outcomes of endoscopic sinus surgery (ESS) on comorbid asthma have been
      relatively well studied, the outcomes of ESS on comorbid bronchiectasis have
      rarely been examined. Objective We sought to determine sinonasal and pulmonary
      clinical outcomes of ESS in bronchiectasis patients with CRS. Method We reviewed
      all bronchiectasis patients who had ESS for CRS at our institution from 2006 to
      present. The sinonasal outcome test 22 (SNOT-22) was administered preoperatively
      and at 3 months, 1 year, and 3 years postoperatively. Pulmonary function tests
      (PFTs) were measured preoperatively and at 6 months and 1 year post operation to
      assess the forced expiratory volume in 1 s (FEV1), forced viral capacity (FVC),
      and FEV1/FVC values. Paired t test and Pearson correlation were used to compare
      pre- and postsurgical results. Results A total of 141 bronchiectasis patients who
      had ESS for CRS were studied. The most common cause of bronchiectasis was cystic
      fibrosis (CF) (42.55%). SNOT-22 scores improved at 3 months post operation and
      were maintained at 1 year and 3 years post operation ( P < .001). All SNOT sub
      domains showed a significant improvement after surgery ( P < .01). However, PFTs
      did not change at 6 months post operation and 1 year post operation ( P > .05).
      There were significant differences in the outcomes in CF versus non-CF patients (
      P < .05) but not by sex or age. Conclusion ESS is effective in improving long
      term sinonasal outcomes in bronchiectasis patients with CRS. However, ESS does
      not appear to improve the pulmonary function.

PMID- 30112922
TI  - Cost-consequence analysis of a hemostatic matrix alone or in combination for
      spine surgery patients.
AB  - BACKGROUND: A five-year retrospective database analysis comparing the use of
      Floseal 1 flowable topical hemostat alone (F) and in combination with
      gelatin/thrombin (F + G/T) to achieve hemostasis and control surgical bleeding
      showed higher resource utilization for F + G/T cases relative to F matched pairs
      during spinal surgery. Lower resource use in the F group was characterized by
      shorter hospital length of stay and surgical time as well as fewer blood
      transfusions and less hemostat agent used per surgery. OBJECTIVE: To evaluate the
      cost-consequence of using F compared to F + G/T in minor, major and severe spinal
      surgery from the US hospital perspective. METHODS: A cost-consequence model was
      developed using the US hospital perspective. Model inputs include clinical inputs
      from the literature, cost inputs (hemostatic matrices, blood product transfusion,
      hospital stay and operating room time) from the literature, and an analysis of
      annual spine surgery volume (minor, major and severe) using the 2012 National
      Inpatient Sample (NIS) database. Costs are reported in 2017 US dollars. One-way
      and probabilistic sensitivity analyses address sources of variability in the
      results. RESULTS: A medium-volume hospital (130 spine surgeries per year) using F
      versus F + G/T for spine surgeries is expected to require 85 less hours of
      surgical time, 58 fewer hospital days and 7 fewer blood transfusions in addition
      to hemostat volume savings (F: 1 mL, thrombin: 1994 mL). The cost savings
      associated with the hospital resources for a medium-volume hospital are expected
      to be $317,959 (surgical hours = $154,746, hospital days = $125,237, blood
      transfusions = $19,023, hemostatic agents = $18,953) or $2445 per spine surgery.
      CONCLUSIONS: The use of F versus F + G/T could lead to annual cost savings for US
      hospitals performing a low to high volume of spinal surgeries per year.

PMID- 30112924
TI  - The Difficulties in Emotion Regulation Scale-Parent Report: A Psychometric
      Investigation Examining Adolescents With and Without ADHD.
AB  - Emotion dysregulation is associated with attention deficit/hyperactivity disorder
      (ADHD) and confers risk for behavior problems and functional impairment; however,
      there is little guidance on best practices for measurement in adolescents. We
      developed a parent-report version of the Difficulties in Emotion Regulation Scale
      (DERS-P). Evidence of reliability and validity was evaluated in a large community
      online sample (Study 1: n = 978; Mage = 13.52 years; SD = 1.93) and in two
      samples of adolescents with ADHD (Study 2, Sample 1: n = 78; Mage = 12.12 years,
      SD = 0.91; Sample 2: n = 206; Mage = 15.35 years; SD = 0.85). A four-factor
      solution of the DERS-P was obtained in Study 1 and confirmed in Study 2, with
      factors demonstrating acceptable internal consistency. The community sample was
      generally rated as less dysregulated than the ADHD samples. Support was obtained
      for convergent, concurrent, and incremental validity evidence. These findings
      provide preliminary evidence for the DERS-P as a psychometrically sound parent
      report measure of emotion dysregulation in 11- to 17-year-old adolescents.

PMID- 30112927
TI  - Synthesis and characterization of photocatalytic polyurethane and poly(methyl
      methacrylate) microcapsules for the controlled release of methotrexate.
AB  - The aim of this work is to prepare ultraviolet (UV) triggered controlled release
      of compounds from microcapsule systems (MCs). Polyurethane (PU) and poly(methyl
      methacrylate) (PMMA) microcapsules were studied with/without chemical
      functionalization using photocatalytic TiO2 nanoparticles (NPs) on their surface.
      Once TiO2 nanoparticles are illuminated with UV light (lambda = 370 nm), they
      initiate the rupture of the polymeric bonds of the microcapsule and subsequently
      initiate the encapsulated compound release, methotrexate (MTX) or rhodamine (Rh),
      in the present work. The size, polydispersity, charge, and yield of all MCs were
      measured, being the methotrexate drug release for all systems determined and
      compared with and without functionalization with TiO2 NPs, under dark, visible
      light and UV illumination in vitro. Finally, the Rh release was characterized
      using fluorescence microscopy. The TiO2 NPs size is around 10 nm, as determined
      by X-ray diffraction experiments. The PU MCs average size is around 60 um, its
      electric charge +3.11 mV and yield around 85%. As for the PMMA MCs, the average
      size is around 280 um, its electric charge -7.2 mV and yield around 25% and 30%
      for both MTX and Rh, respectively. In general, adding TiO2 NPs or the
      encapsulated products to the MCs does not affect the size but functionalization
      with TiO2 NPs lowers the electric charge. Microcapsules functionalized with TiO2
      nanoparticles and irradiated with UV light presented the highest release of MTX
      and Rh. All other samples showed lower drug release levels when studied under the
      same conditions.

PMID- 30112925
TI  - Potential value of patient record review to assess and improve patient safety in
      general practice: A systematic review.
AB  - BACKGROUND: There is limited research, and guidance, on how to address safety in
      general practice proactively. OBJECTIVES: This review aimed to synthesize the
      literature describing the use of patient record review (PRR) to measure and
      improve patient safety in primary care. The PRR methodologies utilized and the
      resulting outcomes were examined. METHODS: Searches were conducted using Medline,
      Embase, CINAHL and PsycINFO in February 2017. Reference lists of included studies
      and existing review papers were also screened. English language, peer-reviewed
      studies that utilized PRR to identify patient safety incidents (PSIs) occurring
      in general practice were included. Two researchers independently extracted data
      from articles and applied the Quality Assessment Tool for Studies with Diverse
      Designs. RESULTS: A total of 3265 studies were screened, with 15 included.
      Trigger tools were the most frequent method used for the PRRs (n = 6). The mean
      number of safety incidents per 100 records was 12.6. Within studies, a mean of
      30.6% of incidents were associated with severe harm (range 8.6-50%), and a mean
      of 55.6% of incidents was considered preventable (range 32.7-93.5%). The most
      commonly identified types of PSIs related to medication and prescribing,
      diagnosis, communication and treatment. Three studies reported on improvement
      actions taken after the PRRs. CONCLUSION: This review suggests that PRR may be a
      promising means of proactively identifying patient safety incidents and informing
      improvements.

PMID- 30112926
TI  - Teaching HIV-specific content for pre-licensure nursing and health professions
      students: a review and synthesis.
AB  - Persistent Human Immunodeficiency Virus (HIV) prevalence rates remain a
      challenge, particularly because health care providers (HCP) are not fully
      prepared to engage in HIV care. This hesitancy to engage creates access to care
      barriers for people living with HIV (PLWH). We conducted a systematic review to
      identify educational interventions focused on developing HIV competencies in
      higher education across health science disciplines. We searched databases for
      primary studies focused on interventions. Using PRISMA guidelines, we identified
      20 articles from 19 distinct studies. While there was an overwhelming body of
      literature that assessed knowledge, skills, and attitudes in health sciences
      students on HIV and AIDS, the low number of intervention studies was notable.
      With the exception of two studies, PLWH were not included in the interventions.
      This finding stands in sharp contrast to the well-established Greater Involvement
      of People Living with HIV and/or AIDS (GIPA) and Meaningful Engagement of People
      Living with HIV and/or AIDS (MEPA) principles. The primary means of the
      educational intervention was focused on delivering lectures to address HIV and
      AIDS knowledge for HCP. There was a significant lack of focus on historical,
      cultural, policy and legal contexts of HIV and AIDS care; theoretical
      justifications for the interventions were absent. No study focused on the impact
      of an intervention on the care provided to PLWH by HCP after graduation. There is
      an urgent need to develop long-term sustainable and scalable interventions that
      address the consistently identified lack of knowledge and skills, and
      stigmatizing attitudes of HCP and students.

PMID- 30112928
TI  - Heterotopic Respiratory Mucosa in the Rectum: An Unusual Type and Site of
      Heterotopia in the Gastrointestinal Tract.
AB  - Although pancreatic and gastric heterotopias are common findings in the
      gastrointestinal tract, heterotopic respiratory mucosa (HRM) in the rectum is
      extremely rare and has only been reported twice previously. We are presenting, to
      our knowledge, the third case of HRM in the rectum. A 56-year-old man with a
      history of chronic diarrhea presented for diagnostic colonoscopy, where he was
      found to have a rectal subepithelial nodule. He was subsequently referred to a
      tertiary medical center for further evaluation with rectal endoscopic ultrasound.
      Endoscopically, the nodule was hypoechoic, 2 to 3 mm in size, located in the
      submucosa, and did not appear to invade the muscularis propria. An uncomplicated
      endoscopic submucosal resection was subsequently performed. Microscopically, the
      nodule showed a multicystic complex lesion located in the submucosa, lined by
      ciliated pseudostratified columnar epithelium and surrounded by thin to
      moderately thick smooth muscle bundles and multiple lobules of seromucinous
      glands. There was associated acute and chronic inflammation. The rectum overlying
      the subepithelial lesion was lined by congested and edematous colonic mucosa and
      demonstrated no connection with the underlying cystic lesion. Immunohistochemical
      stains showed positive p63 basal cell staining in the respiratory epithelium of
      the lesion, while CDX2, TTF-1, and estrogen receptors were all negative. HRM is a
      benign nonneoplastic lesion with unclear etiology. Pathologists and
      gastroenterologists should be aware of this entity and consider it in their
      differential diagnosis for a subepithelial nodule in the rectum, keeping in mind
      that neoplastic processes can also develop in this location.

PMID- 30112929
TI  - Overcoming drug-resistant lung cancer by paclitaxel-loaded hyaluronic acid-coated
      liposomes targeted to mitochondria.
AB  - As a major cause for the inefficiency of cancer chemotherapy, multidrug
      resistance (MDR) has become a major barrier to cancer treatment. Mitochondrion
      orientated transportation of smart liposomes has been developed as a promising
      strategy to deliver anticancer drugs directly to tumor sites and actively target
      the mitochondria, so that drugs can interfere with mitochondrial function and
      facilitate cell apoptosis, overcoming MDR. Herein, we report a novel dual
      functional paclitaxel (PTX) liposome system possessing both CD44-targeting and
      mitochondrial-targeting properties to enhance drug accumulation in mitochondria
      and trigger apoptosis of drug-resistant cancer cells. Mitochondria-targeting PTX
      loaded liposomes were prepared by thin-film hydration and then coated with
      hyaluronic acid (HA) by electrostatic adsorption. We evaluated the
      characteristics of the PTX liposomes in vitro, and found that their particle size
      was about 100 nm and increased to ~140 nm after modification by HA. The
      entrapment efficiency was larger than 85%, and stability data indicated that the
      liposomes were physically and chemically stable for at least one week at 4 
      degrees C. We further evaluated the intake, mitochondrial targeting, ATP levels,
      caspase-3 activity measurement, and antitumor actives of the liposomes. The
      results indicated that HA-coated liposomes with mitochondria targeting had
      significant inhibitory effects against A549 and A549/Taxol cells, showing them to
      be a promising means of improving therapeutic efficacy and overcoming MDR in
      cancer treatment.

PMID- 30112930
TI  - Safety and tolerability of lifitegrast ophthalmic solution 5.0%: Pooled analysis
      of five randomized controlled trials in dry eye disease.
AB  - PURPOSE: Characterize the safety and tolerability of lifitegrast ophthalmic
      solution 5.0% for the treatment of dry eye disease. METHODS: Pooled data from
      five randomized controlled trials were analyzed. Key inclusion criteria were
      adults with dry eye disease (Schirmer tear test score ?1 and ?10 mm, eye dryness
      score ?40 (visual analog scale 0-100), corneal staining score ?2.0 (0-4 scale)).
      Participants were randomized to lifitegrast ophthalmic solution 5.0% or placebo
      twice daily for 84 or 360 days. Treatment-emergent adverse events and drop
      comfort scores were assessed. RESULTS: Overall, 2464 participants (lifitegrast, n
      = 1287; placebo, n = 1177) were included. Ocular treatment-emergent adverse
      events occurring in >5% in either group were instillation site irritation
      (lifitegrast, 15.2%; placebo, 2.8%), instillation site reaction (lifitegrast,
      12.3%; placebo, 2.3%), and instillation site pain (lifitegrast, 9.8%; placebo,
      2.1%); the most common (> 5%) nonocular treatment-emergent adverse event was
      dysgeusia (lifitegrast, 14.5%; placebo, 0.3%). The majority of treatment-emergent
      adverse events were mild to moderate in severity. Discontinuation due to
      treatment-emergent adverse events occurred in 7.0% (lifitegrast) versus 2.6%
      (placebo) of participants (ocular: 5.5% vs 1.5%; nonocular: 1.9% vs 1.1%). Drop
      comfort scores with lifitegrast improved within 3 min of instillation and the
      score at 3 min improved across visits (12-week trials (both eyes, day 84 vs 0):
      2.0 vs 3.3; SONATA (day 360 vs 0): right eye, 1.2 vs 1.7; left eye, 1.2 vs 1.8).
      CONCLUSION: Lifitegrast ophthalmic solution 5.0% appeared to be safe and well
      tolerated for the treatment of dry eye disease. Drop comfort with lifitegrast
      improved within 3 min of instillation.

PMID- 30112931
TI  - The burden of non-infectious intraocular inflammatory eye diseases: a systematic
      literature review.
AB  - OBJECTIVE: Non-infectious inflammatory eye diseases (IEDs), although rare, are
      complex and varied and may result in detrimental effects. A systematic literature
      review was conducted on the clinical outcome and economic burden of IED. METHODS:
      The Ovid search platform (Wolters Kluwer) was used to access scientific
      literature databases, including MEDLINE, Embase, Cochrane libraries, Health
      Technology Assessment and the NHS Economic Evaluation database. The search
      strategy targeted clinical and economic outcomes research in 2009-2016. Titles
      and abstracts resulting from inclusion criteria were screened, and two reviewers
      independently extracted relevant information from the selected full-text
      articles. RESULTS: Thirty-nine papers met the inclusion criteria - 21 clinical
      trials, 7 database analyses, 6 non-systematic literature reviews with expert
      commentary, 3 chart reviews, and 2 surveys - which assessed steroids,
      immunosuppressants, implants and biologics. Patients experienced considerable
      morbidity, much of which was associated with corticosteroid use. The average
      annual healthcare costs of patients with IED were $13,728 to $32,268 in 2009 US
      dollars, which amounted to 3.1 to 8.3 times that of patients without IED. Steroid
      releasing intraocular implants were associated with higher up-front costs, close
      monitoring requirements, potential for implant removal and increased rates of
      adverse ocular events than systemic steroids. CONCLUSIONS: IEDs are rare and
      complex conditions that threaten eyesight and impose considerable morbidity as
      well as a substantial economic burden. This review confirms that further research
      is needed to more fully explore the burden of IED and treatment-related adverse
      events, as well as appropriate means for clinicians to intensify treatment.

PMID- 30112932
TI  - A rare case of pelviureteric junction obstruction in the uncrossed kidney of a
      crossed fused renal ectopia.
AB  - Crossed renal ectopia with fusion is an extremely rare congenital anomaly with
      few reported cases of pelviureteric junction obstruction, which often involves
      the crossed-over kidney. To our knowledge, we describe the second case in
      literature to report an uncrossed kidney with pelviureteric junction obstruction
      and giant hydronephrosis, which obstructs the pelviureteric junction of the
      crossed-over kidney. The grossly hydronephrotic kidney was found to be poorly
      functioning and an aberrant crossing vessel was considered to be potentially
      involved, raising both diagnostic and management challenges. By reporting this
      case, we aim to stress the importance of adequate mapping collecting systems,
      drainage patterns and vascular supply in such crossed fused anomalies.

PMID- 30112933
TI  - Diverticulitis of the transverse colon manifesting as colocutaneous fistula.
AB  - The transverse colon is a particularly rare site for a diverticulum to develop,
      with only few reports of solitary diverticula described in the literature. Among
      the reported complications, colocutaneous fistulas appear relatively
      infrequently. We describe the case of an 80-year-old woman with a solitary
      diverticulum of the transverse colon presenting as acute diverticulitis with
      abscess formation in the epigastric region. A fistulous tract was found between
      the inflamed colon and the skin. A wedge resection of the inflamed colon together
      with the fistula and the solitary diverticulum was performed followed by primary
      suturing of the healthy colonic tissue. Despite the sufficient treatment and
      thorough clearance of the area, the patient died ten days later from ventilator
      associated pneumonia. Although rare, in patients presenting with a subcutaneous
      abscess in the abdominal region, there should be a high level of suspicion for
      active intraperitoneal inflammation derived from complicated diverticular disease
      given the continuously elevated prevalence of the condition in Western societies.
      The decision regarding proper management of this clinical state should be based
      on thorough clinical examination and imaging.

PMID- 30112934
TI  - Late life revision surgery for dilated colonic conduit in long gap oesophageal
      atresia.
AB  - Long gap oesophageal atresia presents a surgical challenge as there is
      insufficient length of the oesophagus to restore continuity. Oesophageal
      replacement is generally achieved using a conduit, taken from the stomach,
      jejunum or colon. Preferences of approach vary between and within surgical
      centres. Specific to colonic interposition, the continued growth and dilation of
      the interposed segment may lead to redundancy. Revision surgery in these cases is
      challenging and has been sparsely described in adult patients. We present two
      patients who had colonic interposition for long gap oesophageal atresia in
      infancy and who then underwent successful revision surgery in their fifth decade.

PMID- 30112935
TI  - Patient positioning for tension band wiring of olecranon fractures.

PMID- 30112936
TI  - Indications and outcomes of home parenteral nutrition in patients with an
      ileoanal pouch.
AB  - INTRODUCTION: Restorative proctocolectomy is a surgical treatment for patients
      with medically refractory ulcerative colitis and some cases of familial
      adenomatous polyposis. Intestinal failure, defined as an inability to maintain
      adequate hydration and micronutrient balances when on a conventionally accepted
      normal diet, is a rare complication of restorative proctocolectomy. We describe
      our experience of patients with restorative proctocolectomy who have developed
      intestinal failure requiring parenteral support. MATERIAL AND METHODS: This was a
      retrospective analysis using a database of patients referred to our intestinal
      failure unit from January 1998 to January 2016. We analysed the records of all
      those patients who had restorative proctocolectomy who developed intestinal
      failure. RESULTS: 807 patient records analysed, 35 patients were found to have
      had a restorative proctocolectomy (13 male and 22 female). Ninety-one percent (n
      = 32) of patients developed IF as a consequence of unpredictable complications
      which occurred after RPC formation. Potentially predictable complications were
      noted in 9% (n = 3) of patients. DISCUSSION AND CONCLUSIONS: Most cases of
      intestinal failure in restorative proctocolectomy were unpredictable. In a small
      number of patients, accurate assessment and measurement of the small intestine
      may have better predicted the adverse outcome of intestinal failure allowing
      improved pre-operative counseling of patients.

PMID- 30112937
TI  - A rare complication of ileostomy obstruction: Boerhaave syndrome.
AB  - Small bowel obstruction is the most common surgical emergency after a patient has
      had abdominal surgery. However, Boerhaave syndrome secondary to an ileostomy
      obstruction has not been reported in current literature. We present a rare case
      of two concurrent surgical emergencies in a patient with Boerhaave syndrome and
      small bowel obstruction. A 38-year-old woman presented with sudden onset severe
      central chest pain associated with breathlessness. She had a history of Crohn's
      disease, which had been treated with pancolectomy and ileostomy. Clinical
      examination showed an extensive palpable surgical emphysema extending from the
      neck to the pelvis with a distended abdomen. Computed tomography contrast of the
      chest and abdomen reported bilateral pneumothoraces, ruptured oesophagus and
      distended small bowel secondary to obstruction at the ileostomy. She was referred
      to the nearest cardiothoracic centre for an urgent assessment. Unfortunately she
      passed away shortly after the scan. Ruptured oesophagus is associated with a high
      mobidity and mortality if it is not recognised, so early diagnosis and prompt
      treatment is crucial in reducing the mortality rate. There is a strong
      association between stoma formation and incidence of small bowel obstruction but
      no difference between an ileostomy and colostomy. This case helps to illustrate
      the challenging management of chronic recurring abdominal obstruction and the
      delicate balance of risk of complication versus benefit of various management
      being surgical or conservative. All general surgeons should be wary of the
      potential complication of oesophageal perforation secondary to intestinal
      obstruction.

PMID- 30112938
TI  - A modified approach from the edge of the tragus in the surgical treatment of
      mandibular condyle fractures.
AB  - Introduction We present our experiences using a modified surgical approach from
      the edge of the tragus for mandibular condyle fractures, to reduce the risk of
      postoperative complications and visible scars. Materials and methods Thirty-two
      patients presenting with mandibular condyle fractures were treated through a
      modified approach on the edge of the tragus. The age of the patients ranged from
      6 to 62 years. All mandibular condyle fractures were fixed. The patients were
      asked to start open-mouth training one week postoperatively, undergoing a cone
      beam computed tomography examination and clinical follow-up. Postoperative
      complications were evaluated after surgery. Results Mouth opening was normal
      (average 39.5 mm) in all the patients during the operation and the occlusion
      improved significantly compared with preoperatively. No cases of damaged facial
      nerves were observed during the final follow-up at six months and postoperative
      scars were less noticeable. Conclusions The modified surgical approach from the
      edge of the tragus for mandibular condyle fractures provides a good view of the
      operative field, reduces the risk of facial nerve damage and produces a less
      noticeable postoperative scar.

PMID- 30112940
TI  - Radiolucent triangle and U-bolster for lower leg positioning for circular frame
      application.

PMID- 30112939
TI  - Bariatric fellowship positively influences early outcomes for laparoscopic Roux
      en-Y gastric bypass surgery over seven years of independent practice.
AB  - Introduction Laparoscopic Roux-en-Y gastric bypass (LRYGB) is technically
      demanding and has an associated learning curve. We published previously that
      bariatric fellowship reduces the learning curve of primary LRYGB and improves
      patient outcomes after one year of independent practice. However, the long-term
      effect of fellowship is unknown. We therefore aimed to compare the 30-day
      outcomes of LRYGB between the first year of a surgeon's independent practice with
      the subsequent six years. Materials and methods A prospective database of
      patients undergoing primary LRYGB under a single surgeon from March 2010 until
      February 2017 was analysed. Two groups were studied: first year (< 1 year) and
      the subsequent six years (>= 1 year) of independent practice. Patient
      demographics, length of hospital stay, conversion to open surgery, perioperative
      complications and mortality were compared. Results Among 279 eligible patients,
      74 (26.5%) were in the < 1 year group and 205 (73.5%) in >= 1 year group. The
      preoperative risk scores, American Society of Anesthesiologists (ASA) grade, P =
      0.00; obesity surgery mortality risk score (OS-MRS), P = 0.04) were significantly
      higher in >= 1 year group. There was no significant difference in perioperative
      outcomes (length of stay, P = 0.38; total complications, P = 0.20; readmissions,
      P = 1.00; reoperations, P = 0.60) between the two groups. Conclusions Bariatric
      fellowship reduces the learning curve for LRYGB and helps to achieve excellent
      outcomes in the first and subsequent years of independent practice. The higher
      risk profile of >= 1 year group did not equate to an increase in complications,
      suggesting that experience and standardisation may help in handling complex
      cases. To our knowledge, this represents the only such study in the literature.

PMID- 30112941
TI  - A five-year follow-up observational study of the T-14 paediatric throat disorders
      outcome measure in tonsillectomy and adenotonsillectomy.
AB  - Introduction The T-14 questionnaire is a validated outcome measurement tool to
      assess the value of paediatric tonsillectomy from a parent's perspective. There
      is a paucity of data regarding the long-term postoperative effects of
      tonsillectomy on quality of life in the paediatric population. Our previous study
      assessed T-14 scores up to year 2 postoperatively, with this study extending
      follow-up to 5 years. Materials and methods We undertook a prospective
      uncontrolled observational study examining 54 paediatric patients undergoing
      tonsillectomy at Portsmouth Hospitals NHS Trust. Parents of children undergoing
      surgery were invited to complete a T-14 questionnaire preoperatively, as well as
      at 3 months, 6 months, 1 year, 2 years and now 5 years postoperatively. Results
      In total, 44 of 54 patients completed questionnaires preoperatively and at all
      postoperative time points, with 46 being completed at 5 years. There was a highly
      significant (P < 0.001) difference between the preoperative scores and all other
      measured T-14 scores postoperatively. The mean score preoperatively was 33.3
      compared with 1.0 at 5 years. Conclusions This is the first study to assess long
      term quality of life following paediatric tonsillectomy using the T-14
      questionnaire. The benefits of tonsillectomy on long-term quality of life further
      confirms its value within the paediatric population.

PMID- 30112942
TI  - Hemiarthroplasty compared with total hip arthroplasty in fractured neck of femur:
      a shift in national practice?
AB  - Introduction The aim of this study was to determine the trends in national
      practice regarding total hip arthroplasty compared with hemiarthroplasty in
      fractured neck of femur between 2010 and 2016. Materials and methods A
      retrospective review was conducted of NHS Digital data (England) between 2010 and
      2016. 'Emergency' neck of femur fracture admissions, hemiarthroplasties and total
      hip arthroplasties were included. Elective total hip arthroplasties, revisions
      and prostheses relocations were excluded. Annual percentages for each operation
      were calculated. Trends were tabulated and displayed graphically for analysis.
      Results The total number of emergency neck of femur diagnoses was 257,789. Total
      hip arthroplasty was performed in 2217, 2737, 3305, 3686, 3670 and 3825 patients
      and hemiarthroplasty was performed in 21,335, 21,744, 21,115, 21,798, 21,804 and
      22,163 patients for each year between 2011 and 2016, respectively. The rate of
      change for total hip arthroplasty slowed from 24.54% increase/year (2011-2013) to
      5.24% increase/year (2013-2016). Uncemented arthroplasties decreased over the
      same time period. Discussion Increasing numbers of total hip arthroplasties are
      conducted for hip fractures; however, this trend has slowed since 2013. Possible
      explanations include all eligible fractures being treated with total hip
      arthroplasty, trauma surgeon preference for hemiarthroplasty due to lower
      surgical specialism or publication of individual surgeon data (National Joint
      Registry) which may lead to surgeons favouring hemiarthroplasties which have a
      lower complication rate compared to elective total hip arthroplasties.

PMID- 30112944
TI  - Mediastinal herniation of the biliary tract leading to bile duct: obstruction
      following oesophagectomy.
AB  - Surgical management of oesophageal and gastro-oesophageal junction malignancies
      is one of the most challenging situations confronting the surgeon. Attaining a
      complete circumferential resection margin of lower-third oesophageal and gastro
      oesophageal junction locally advanced carcinomas requires en-bloc resection of
      the hiatus and all the peri-oesophageal tissue and pleura. This results in an
      increased risk of herniation of the abdominal organs through the enlarged hiatus,
      which carries significant risk of morbidity and mortality. The incidence of this
      complication is higher than has been reported. Surgical management of symptomatic
      hernias is the standard treatment while criteria for managing asymptomatic
      hernias are less clear. We report a rare case of a late mediastinal herniation of
      the pancreas and bile duct, leading to obstructive jaundice following
      oesophagectomy which was treated successfully in our unit.

PMID- 30112943
TI  - Cup-on-cup technique to manage severe protrusio acetabular defects.
AB  - Previous studies have demonstrated that revision of total hip arthroplasty
      consumes considerably more resources than the primary procedure. Worse, patients
      who need revision procedures are more likely to have radiographic evidence of
      acetabular and femoral bone loss than those undergone primary total hip
      arthroplasty. Many techniques have been introduced to manage different conditions
      of acetabular deficiencies. We describe a rare case of a 67-year-old man with
      severe acetabular bone loss, which was caused by a long-term loose acetabular
      component and was successfully managed by cup-on-cup technique. We also discuss
      the similarities and differences between cup-on-cup and cup-in-cup techniques in
      the management of protrusio acetabular defects, with a case-based approach.

PMID- 30112945
TI  - Laparoscopic inguinal hernia repair: a rare case of colonic mesh migration.
AB  - Inguinal hernia repair can be performed via either an open or laparoscopic
      technique. Use of a mesh to repair the abdominal wall defect is now common
      practice, leading to a reduction in hernia recurrence but also associated with a
      number of complications. We report a rare case of a 49-year old man who presented
      3 years after laparoscopic hernia repair with right-sided abdominal pain and
      loose stools. Colonoscopy and computed tomography revealed a mesh and fixation
      devices within the lumen of the caecum and ascending colon. The mesh was
      successfully excised with primary closure of the bowel defect. This case
      highlights the importance of recognising mesh migration as a complication of
      hernia repair, a phenomenon which can lead to serious morbidity. We suggest that
      patients should be informed of this risk during the consent process, while
      further research is needed to investigate how this occurrence can be prevented.

PMID- 30112946
TI  - Novel technique for laparoscopic common bile duct exploration using disposable
      bronchoscope.

PMID- 30112947
TI  - Fracture of the tibial tubercle with a Stener-like lesion of the patellar tendon:
      a case report.
AB  - Fractures of the tibial tubercle account for less than 1% of paediatric
      orthopaedic injuries. We report a case of a 15-year-old boy presenting with a
      Stener-like lesion of the patellar tendon associated with a fracture of the
      tibial tubercle. There have been no previously reported cases of this type of
      injury in the literature. Treatment with open reduction and internal fixation of
      the fracture along with a repair of the patellar tendon can result in an
      excellent functional outcome.

PMID- 30112949
TI  - Radial forearm free flap as the last resort for oesophageal reconstruction.
AB  - Strategies for oesophageal reconstruction following resection vary according to
      the nature of the pathology encountered, patient factors and surgeon preference.
      However, reconstruction in patients with multiple previous failed attempts poses
      specific management challenges. We present the case of a 61-year-old man who
      underwent oesophageal reconstruction with a radial forearm flap as a last resort.

PMID- 30112950
TI  - Combination of acellular dermal matrix with a de-epithelialised dermal flap
      during skin-reducing mastectomy and immediate breast reconstruction.
AB  - Introduction Patients with large ptotic breasts undergoing immediate implant
      based reconstruction often require skin-reducing mastectomy to optimise the
      aesthetic outcome. However, healing complications, especially at the resulting
      inverted T-junction, leading to wound dehiscence, infection, skin necrosis,
      implant exposure and failed reconstruction have been widely reported. We present
      an innovative approach for immediate implant-based reconstruction combining
      porcine- or bovine-derived acellular dermal matrices with a de-epithelialised
      dermal sling to protect and support the implant, while improving clinical
      outcomes in this challenging group of patients. Materials and methods
      Demographic, tumour and surgical data were reviewed for patients undergoing Wise
      pattern (T-scar) skin-reducing mastectomies with immediate implant-based
      reconstruction combining porcine- or bovine-derived acellular dermal matrices
      with a de-epithelialised dermal sling. Results This technique was successfully
      employed to reconstruct five large pendulous breasts in four breast cancer
      patients with a median age of 50.5 years (range 34-61 years) who were not
      suitable for, or had declined, flap-based reconstruction. The acellular dermal
      matrices used were SurgiMend(r), StratticeTM and Braxon(r) and the expandable
      implants were placed in the sub-pectoral (n = 3) and pre-pectoral (n = 1) planes.
      The technical steps and clinical outcomes are presented. One patient experienced
      T-junction breakdown overlying the de-epithelialised dermis without implant loss.
      Conclusion The combination of an acellular dermal matrix and a dermal sling
      provides a double-layer 'water-proofing' and support for the implants inferiorly,
      avoiding T-junction breakdown complications, since any dehiscence is on to well
      vascularised dermis. Furthermore, the acellular dermal matrix stabilises the
      implant in the large mastectomy cavity (pocket control). This approach provides a
      viable option which facilitates mastectomy and immediate implant reconstruction
      in large-breasted patients.

PMID- 30112948
TI  - The incidence of stoma related morbidity - a systematic review of randomised
      controlled trials.
AB  - Introduction Several stoma related complications can occur following ileostomy or
      colostomy formation. The reported incidence of these conditions varies widely in
      the literature. A systematic review of randomised controlled trials reporting the
      incidence of stoma related complications in adults was performed to provide the
      most comprehensive summary of existing data. Methods PubMed, CINAHL(r)
      (Cumulative Index to Nursing and Allied Health Literature) and the Cochrane
      Library were searched for trials assessing the incidence of complications in
      adults undergoing conventional stoma formation. Data were extracted by two
      independent reviewers and entered into SPSS(r) for statistical analysis. The
      Cochrane Collaboration tool for assessing risk of bias was used to critically
      appraise each study. Cochran's Q statistic and the I2 statistic were used to
      measure the level of heterogeneity between studies. Results Overall, 18 trials
      were included, involving 1,009 patients. The incidence of stoma related
      complications ranged from 2.9% to 81.1%. Peristomal skin complications and
      parastomal hernia were the most common complications. End colostomy had the
      highest incidence of morbidity, followed by loop colostomy and loop ileostomy.
      There were no trials involving patients with end ileostomy. There was a high
      level of detection bias and heterogeneity between studies. Conclusions This
      systematic review has summarised the best available evidence concerning the
      incidence of stoma related morbidity. The high level of heterogeneity between
      studies has limited the accuracy with which the true incidence of each stoma
      related complication can be reported. Large, multicentre trials investigating
      homogenous participant populations are therefore required.

PMID- 30112952
TI  - ENT in the context of global health.
AB  - Global health is a fashionable term frequently used in the twenty-first century's
      news that is rarely understood by ear, nose and throat (ENT) professionals.
      Communicable diseases such as HIV, tuberculosis and malaria have been in the
      headlines of global health for decades. Despite the recent public health concerns
      about noncommunicable diseases, including ENT disorders, these disorders still
      receive little attention on the global health stage. Despite the 'benign' nature
      and a large number of patients affected at a given time, noncommunicable diseases
      were found to account for 60% of international mortality in 2008. More
      specifically to ENT, disabling hearing impairment has been found to be the most
      common disability globally. Therefore, it is now critical for otolaryngologists
      worldwide to get involved in the overlooked ENT global issues. This article
      discusses the main challenges faced by the ENT community in the developing world
      and proposes what can be done to help.

PMID- 30112951
TI  - A curious case of cololithiasis.
AB  - Gallstone ileus is an uncommon cause of bowel obstruction that involves
      cholecystoenteric fistulation and resultant passage of gallstones into the bowel.
      In the vast majority of cases, the fistula forms between the gallbladder and
      duodenum leading to small bowel obstruction. We report a case of cholecystocolic
      fistulation and subsequent large-bowel obstruction in a 75-year-old woman who
      presented acutely after taking a bowel preparation for an outpatient colonoscopy
      during the course of an investigation of anaemia and nonspecific abdominal pain.
      Preintervention imaging revealed a giant gallstone at the rectosigmoid junction,
      in the presence of a cholecystocolic fistula, and subsequent large bowel
      obstruction. After a failed period of expectant management, laparotomy and
      Hartmann's procedure were performed and the patient made an uneventful recovery.

PMID- 30112953
TI  - Laparoscopic retraction in Nissen fundoplication for the patient who is latex
      allergic.

PMID- 30112954
TI  - Triceps on, alignment off? A comparison of total elbow arthroplasty component
      positioning with a triceps-on and a triceps-off approach.
AB  - Introduction This retrospective review investigates whether the triceps-on
      approach obtains alignment of total elbow arthroplasty implants equivalent to a
      triceps-off approach. Methods The last 30 consecutive total elbow arthroplasties
      performed by the senior author were reviewed to identify the approach used and
      pathology treated. Initially, a triceps split and reflection approach was used,
      then a triceps-preserving approach. Two blinded reviewers measured the component
      alignment in standardised radiographs. Pearson's correlation coefficient was
      calculated to investigate inter/intra-observer and error. The two groups were
      compared using an unpaired Student t-test. Results There were 13 elbows in the
      triceps-off group and 17 in the triceps-on group. Pearson's coefficient was 0.75
      for interobserver error, 0.89 for intra-observer error. There was no statistical
      difference between the achieved alignment. All ulna components were flexed with a
      mean angle deviation of 4.5 degrees in the triceps-off group and 5.7 degrees in
      the triceps on. Two (15%) ulna components in the triceps-off group were placed in
      over 5 degrees of flexion, compared with seven (44%) in the triceps-on group.
      Conclusion These results demonstrate no statistical difference in the achieved
      alignment between the two groups. Surgeons should beware of the tendency to place
      the ulna component in a flexed position, especially in the triceps-on approach.

PMID- 30112956
TI  - Three cases of antibody-LGI1 limbic encephalitis and review of literature.
AB  - Antibody-LGI1 limbic encephalitis(LGI1-Ab LE) is an anti-neuronal surface antigen
      related autoimmune encephalitis, which clinically manifests through memory
      impairment, faciobrachial dystonic seizures (FBDS), epileptic seizures, behavior
      disorders, and hyponatremia. Now, we reported three cases of LGI1-Ab LE. The
      clinical features of our patients presented with memory impairment, epileptic
      seizures, hyponatremia, and two patients presented with behavior disorders. All
      serum LGI1 antibodies were positive, whereas one patient LGI1 antibodies of
      cerebrospinal fluid (CSF) was negative. Gammaglobulin, hormone or both in
      combination were administered to them, the clinical symptoms improved
      significantly.

PMID- 30112955
TI  - Splenic trauma in the twenty-first century: changing trends in management.
AB  - Over the past three decades, management of blunt splenic trauma has changed
      radically. Use of improved diagnostic techniques and proper understanding of
      disease pathology has led to nonoperative management being chosen as the standard
      of care in patients who are haemodynamically stable. This review was undertaken
      to assess available literature regarding changing trends of management of blunt
      splenic trauma, and to identify the existing lacunae in nonoperative management.
      The PubMed database was searched for studies published between January 1987 and
      August 2017, using the keywords 'blunt splenic trauma' and 'nonoperative
      management'. One hundred and fifty-three articles were reviewed, of which 82 free
      full texts and free abstracts were used in the current review. There is clear
      evidence in published literature of the greater success of nonoperative over
      operative management in patients who are haemodynamically stable and the
      increasing utility of adjunctive therapies like angiography with embolisation.
      However, the review revealed a lack of universal guidelines for patient selection
      criteria and diagnostic and grading procedures needed for nonoperative
      management. Indications for splenic artery embolisation, the current role of
      splenectomy and spleen-preserving surgeries, together with the place of minimal
      access surgery in blunt splenic trauma remain grey areas. Moreover, parameters
      affecting the outcomes of nonoperative management and its failure and management
      need to be defined. This shows a need for future studies focused on these
      shortcomings with the ultimate aim being the formulation and implementation of
      universally accepted guidelines for safe and efficient management of blunt
      splenic trauma.

PMID- 30112959
TI  - Use of disease-modifying anti-rheumatic or anti-tumour necrosis factor drugs and
      risk of hospitalized infection in ankylosing spondylitis.
AB  - OBJECTIVE: To assess the risk of hospitalized infection among initiators of
      disease-modifying anti-rheumatic drugs (DMARDs) and/or anti-tumour necrosis
      factor (anti-TNF) agents in ankylosing spondylitis (AS). METHOD: We studied AS
      patients, new users of anti-TNF drugs and/or DMARDs between 1 January 2001 and 31
      December 2011. Cohort entry was defined as the date of first prescription of any
      of these drugs. We used Cox regression with three time-varying drug exposures:
      current use of DMARDs without biologics, current use of anti-TNF agents alone or
      in combination with DMARDs (anti-TNF +/- DMARDs), and current non-use. Models
      were adjusted for baseline patient sociodemographic characteristics, comorbidity,
      outpatient visits and procedures, previous infection, non-steroidal anti
      inflammatory drugs, and corticosteroids. Hospitalized infection was defined on
      the basis of hospitalization discharge diagnoses (primary or non-primary) coding
      for infection. RESULTS: The cohort included 747 AS patients, with a mean age of
      51.1 years (sd 14.6), and 466 (62.4%) were men. During the median follow-up of
      1.98 years, 57 hospitalized infections occurred, for an incidence rate of 2.9/100
      person-years. The adjusted hazard ratio of infection (relative to unexposed) was
      1.00 [95% confidence interval (CI) 0.47-2.11] for the anti-TNF +/- DMARDs group
      and 0.96 (95% CI 0.45-2.04) for DMARDs alone. Use of healthcare, corticosteroids,
      and previous hospitalized infections were associated with infection. CONCLUSION:
      We found no clear evidence that the risk of hospitalized infection was linked to
      DMARD and/or anti-TNF drug use. Because of scarce published literature on
      infection risk in AS patients, our results have important implications for
      clinicians.

PMID- 30112958
TI  - Parametric effect of vibrational drilling on osteonecrosis and comparative
      histopathology study with conventional drilling of cortical bone.
AB  - Drilling to the bones is required to re-fix them at their appropriate location
      using the implants. During drilling some thermal and mechanical losses may be
      faced by the bone and surrounding tissues which may lead to the serious issue in
      terms of osteonecrosis. Osteonecrosis is one of the reasons for impaired healing
      process for the fractured bone and causes further complications like low pullout
      strength of cortical screws and bone crush. In order to maintain the low
      temperature during bone drilling, this study focused the thermal damages observed
      by the bone and its surrounding during bone drilling and compared the results of
      conventional and vibrational drilling techniques. Parametric optimization under
      the influence of vibrations was also studied. Drilling has been done with the
      both drilling technique, and results were recorded in terms of temperature raise.
      Optimal solution for drilling the bone has been accessed using Taguchi
      optimization technique. The morphological comparison has been done for
      conventional and vibrational drilled holes using histopathology of drilled bones
      sections. From Taguchi optimization, it was observed that R1F1A1 is the
      parametric combination which gives minimum thermal injury to the bone in case of
      vibrational bone drilling. Analysis of variance cleared that the all parameters
      involved significantly affect the results (P <= 0.05). Rotational speed was found
      to be the most influential factor among the all with 80.53%. Histopathology
      studies of bone specimens help to understand how heat generation affects the bone
      morphology during drilling. The specimens drilled with vibrational drilling show
      less damage in terms of osteonecrosis near the drill site which shows the
      significance of vibrational drilling in case of orthopedic surgeries. The raise
      in temperature during drilling is collective result of different drilling
      parameters. Vibrational drilling was observed a helping tool to control the
      thermal damage in bone drilling.

PMID- 30112957
TI  - Pathological correlates of white matter hyperintensities in a case of progranulin
      mutation associated frontotemporal dementia.
AB  - White matter hyperintensities (WMH) are often seen on MRI brain scans in
      frontotemporal dementia (FTD) due to progranulin (GRN) mutations, but their
      pathological correlates are unknown. We examined the histological changes
      underlying WMH in a patient with GRN mutation associated behavioral variant FTD.
      In vivo and cadaveric MRI showed progressive, asymmetric frontotemporal and
      parietal atrophy, and asymmetrical WMH predominantly affecting frontal mid-zones.
      We first performed segmentation and localization analyses of WMH present on
      cadaveric MRI FLAIR images, then selected five different brain regions directly
      matched to differing severities of WMH for histological analysis. We used
      immunohistochemistry to assess vascular pathology, degree of spongiosis, neuronal
      and axonal loss, TDP-43, demyelination and astrogliosis, and microglial burden
      and morphology. Brain regions with significant WMH displayed severe cortical and
      white matter pathology, and prominent white matter microglial activation and
      microglial dystrophy, but only mild axonal loss and minimal vascular pathology.
      Our study suggests that WMH in GRN mutation carriers are not secondary to
      vascular pathology. Whilst cortical pathology induced axonal degeneration could
      contribute to white matter damage, individuals with GRN mutations could develop
      selective white matter vulnerability and myelin loss due to chronic, regional
      microglial dysfunction arising from GRN haploinsufficiency.

PMID- 30112960
TI  - Urban public parks and mental health in adult women: Mediating and moderating
      factors.
AB  - BACKGROUND:: The association of green spaces such as urban public parks and
      mental health might vary according to personal characteristics and
      characteristics of the park and be mediated by the use of the park. AIMS:: We
      investigate the association between urban public park coverage and mental health
      in adult women, the moderation of this association by personal and park-related
      characteristics, and the mediation of the association by use of public space.
      METHODS:: Combining data from a cross-sectional survey of the adult female
      population of Tijuana (Mexico) in 2014, and a study of public spaces in 2013, we
      analyzed the association between park coverage in buffers of 400 and 800 m from
      participants' homes and score in the Center for Epidemiologic Studies-Depression
      scale (CES-D). We tested for mediation by use of park and interaction of urban
      park coverage with personal and park characteristics. RESULTS:: Urban public park
      coverage in the 400-m buffer had an inverse association with CES-D score that was
      moderated by age (significant only for younger participants), with no evidence of
      mediation. Park coverage in the 800-m buffer also had an inverse association with
      CES-D score, moderated by age and occupation (significant for younger
      participants and homemakers), and a mediated association was also observed. There
      was no interaction between park coverage and park characteristics in their
      association with CES-D score. CONCLUSION:: Our results confirm the potential of
      public parks to improve mental health and suggest that this effect could be more
      important at some stages in the life course for women. The upper-middle-income,
      Latin American country setting adds to the current knowledge that is mostly based
      on high-income countries.

PMID- 30112961
TI  - Molecular Biological Tools in Concrete Biodeterioration - A Mini Review.
AB  - Concrete structures develop biofilms when exposed to various environments. At a
      certain stage, the microbial films destroy the concrete structures leading to
      significant deterioration. Culture-dependent techniques give an incomplete
      picture of the microbial communities on the concrete surface. Culture independent
      techniques or molecular biological tools pave a new way to analyze microbial
      communities involved in concrete biodeterioration. This study highlights the need
      to 'build' a database, for Microbiologically Influenced Concrete Corrosion (MICC)
      involving microbial groups that are being identified using culture dependent and
      independent techniques. The role of molecular tools such as 16S rRNA sequencing,
      denaturing gradient gel electrophoresis (DGGE), Fluorescent in situ hybridization
      (FISH), Real time Polymerase Chain Reaction (RT-PCR), microarray analysis, 2
      Dimensional gel electrophoresis (2-DE) in analyzing microbial communities on the
      concrete structures have been reviewed in this paper.

PMID- 30112963
TI  - Imaging Brain Metabolism in the Newborn.
AB  - In this review, we discuss molecular brain imaging studies using positron
      emission tomography (PET) with 2-deoxy-2(18F)fluoro-d-glucose (FDG) in human
      newborns and infants, and illustrate how this technology can be applied to probe
      the neuropathophysiology of neonatal neurologic disorders. PET studies have been
      difficult to perform in sick babies because of patient transportation issues and
      suboptimal spatial resolution. With approval from the FDA and the institutional
      review board, we modified and installed the Focus 220 animal microPET scanner
      (Concorde Microsystems, Knoxville, TN) directly in our neonatal intensive care
      unit in Children's Hospital of Michigan and verified the high spatial resolution
      (<2 mm full-width-at-half-maximum) of this microPET. The neonatal pattern of
      glucose metabolism is very consistent, with the highest degree of activity in
      primary sensory and motor cortex, medial temporal region, thalamus, brain stem,
      and cerebellar vermis. Prior studies have shown that increases of glucose
      utilization are seen by 2 to 3 months in the parietal, temporal, cingulate, and
      primary visual cortex; basal ganglia; and cerebellar hemispheres. Between 6 and 8
      months, lateral and inferior frontal cortex becomes more functionally active and,
      eventually, between 8 and 12 months, the dorsal and medial frontal regions also
      show a maturational increase. These findings are consistent with the physical,
      behavioral, and cognitive maturation of the infant. At birth, metabolic rates of
      glucose utilization in cortex are about 30% lower than in adults but rapidly rise
      such that, by 3 years, the cerebral cortical rates exceed adult rates by more
      than 2-fold. At around puberty, the rates for cerebral cortex begin to decline
      and gradually reach adult values by 16-18 years. These nonlinear changes of
      glucose utilization indirectly reflect programed periods of synaptic
      proliferation and pruning in the brain. Positron emission tomographic (PET)
      imaging of GABAA receptors (using 11C-flumazenil) in newborns also show a pattern
      very different from adults, with high binding in amygdala-hippocampus, sensory
      motor cortex, thalamus, brain stem, and basal ganglia, in that order. We
      speculate that the early development of amygdala/hippocampus prepares the baby
      for bonding, attachment, and memory, and the deprivation of such experiences
      during a sensitive period results in malfunction of these networks and
      psychopathology, as has been shown in studies on severely socioemotionally
      deprived children. Recently developed hybrid PET/magnetic resonance (MR) scanners
      allow the simultaneous acquisition of PET and MR data sets with advanced
      applications. These devices are particularly advantageous for scanning babies and
      infants because of the high spatial resolution, automated coregistration of
      anatomical and functional images and, in the case of need for sedation, maximal
      data acquired in 1 session.

PMID- 30112964
TI  - Application of recycling waste products for ex situ and in situ water treatment
      methods.
AB  - The specific objectives of the study were to determine the approximate design
      parameters for filter bed and highlight the possible scope of using mixed iron
      oxides rich smelter slag for in situ or ex situ treatment. The batch and column
      study was conducted to assess the As removal capacities from contaminated water.
      X-ray fluorescence (XRF) analysis of the slag waste product determined the
      presence of large quantities of iron (Fe). In this study, the maximum removal
      capacities were found to be approximately 1.78 mg As per g of slag and 100%
      removal of As(V) was achieved during the first 30 days of three column
      operations. The changes in redox potential (Eh) values and the changes in
      effluent pH throughout the column operation period indicated redox reactions
      occurring in the system. The column experiments were modelled using a semi
      analytic solution to the advection-dispersion-adsorption equation incorporated in
      the commercial software, Pollute V7. From the best-fit of the modelling results
      to the experimental breakthrough curves, the hydrodynamic dispersion coefficient
      (D) was found to be 0.0115 and 0.00775 m2/day for column 1 and column 2,
      respectively, and 0.00862 m2/day for column 3. The values of the distribution
      coefficient (KD) were 0.18, 0.173 and 0.171 m3/kg or L/g for the three columns
      and 0.24 L/g from the batch test. The results from the experiments may be used to
      aid the design of a filter bed or reactive barrier in a scenario where the mixed
      iron oxides rich smelter waste product is used as a candidate reactive medium.

PMID- 30112962
TI  - Childhood violence and mental health among indigenous Sami and non-Sami
      populations in Norway: a SAMINOR 2 questionnaire study.
AB  - : The main objectives of this study were to investigate the association between
      childhood violence and psychological distress and post-traumatic stress symptoms
      (PTS) among Sami and non-Sami adults, and to explore a possible mediating effect
      of childhood violence on any ethnic differences in mental health. This study is
      part of a larger questionnaire survey on health and living conditions in Mid- and
      Northern Norway (SAMINOR 2) which included 2116 Sami and 8674 non-Sami
      participants. A positive association between childhood violence and psychological
      distress and PTS in adulthood was found regardless of ethnicity. For women,
      childhood violence may have mediated some of the ethnic differences in
      psychological distress (53.2%) and PTS (31.4%). A similar pattern was found for
      men as to psychological distress (45.5%) and PTS (55.5%). The prevalence of
      psychological distress was significantly higher in the Sami than in the non-Sami
      group: 15.8% vs. 13.0% for women, and 11.4% vs. 8.0% for men. Likewise, PTS
      showed a higher prevalence in the Sami group, both for women (16.2% vs. 12.4%)
      and for men (12.2% vs. 9.1). CONCLUSION: A positive association between childhood
      violence and adult mental distress was found for both Sami and Norwegian adults.
      More mental problems were found among the Sami. Childhood violence may have
      mediated some of the ethnic differences.

PMID- 30112967
TI  - Current Therapeutic Approaches in Leukodystrophies: A Review.
AB  - Leukodystrophies are a heterogeneous class of genetic diseases affecting the
      white matter in the central nervous system with a broad range of clinical
      manifestations and a frequently progressive course. An interest in precision
      medicine has emerged over the last several decades, and biomedical research in
      leukodystrophies has made exciting advances along this front through therapeutic
      target discovery and novel disease model systems. In this review, we discuss
      current and emerging therapeutic approaches in leukodystrophies, including gene
      therapy, antisense oligonucleotide therapy, CRISPR/CAS-based gene editing, and
      cell and stem cell based therapies.

PMID- 30112965
TI  - The Experiences of Gay and Bisexual Men Post-Prostate Cancer Treatment: A Meta
      Synthesis of Qualitative Studies.
AB  - Studies suggest that gay and bisexual men are affected by the psychological
      aspects of prostate cancer treatment differently than that of heterosexual men;
      however the data have not yet been synthesized. The focus of this meta-synthesis
      is to explore gay and bisexual men's experiences of prostate cancer
      posttreatment. Empirical research published in peer reviewed journals between
      January 1990 and January 2018 were identified in six databases: CINAHL, Cochrane,
      Medline, PsycINFO, PubMed, and Web of Science. Titles and abstracts were checked
      by two reviewers. The six studies that met the inclusion criteria were selected
      and reviewed for quality and the extracted data were then synthesized. The main
      themes that emerged were sexual impact, physical and psychological difficulties,
      challenges to intimacy, and support mechanisms. Gay and bisexual men can have
      specific sexual roles and developing prostate cancer and undergoing treatment may
      compromise their ability to perform their sexual role. The needs of heterosexual
      men were perceived to be accommodated more often than that of gay and bisexual
      men because of engrained heteronormativity in the health-care system. The review
      suggests that more support groups specifically for gay and bisexual men should be
      established, while urologists should cater to the sexual and masculine
      implications of treatment, and not frame problems for gay and bisexual men in
      heterosexual terms. By failing to address the salient needs and concerns of gay
      and bisexual men, health-care professionals are reinforcing invisibility and
      marginalization of gay and bisexual men with prostate cancer.

PMID- 30112968
TI  - Negotiating the Intersection of Science and Commerce.

PMID- 30112966
TI  - 6-Hydroxydopamine induces secretion of PARK7/DJ-1 via autophagy-based
      unconventional secretory pathway.
AB  - : PARK7/DJ-1 is a Parkinson disease- and cancer-associated protein that functions
      as a multifunctional protein involved in gene transcription regulation and anti
      oxidative defense. Although PARK7 lacks the secretory signal sequence, it is
      secreted and plays important physiological and pathophysiological roles. Whereas
      secretory proteins that lack the endoplasmic reticulum-targeting signal sequence
      are secreted from cells by way of what is called the unconventional secretion
      mechanism, the specific processes responsible for causing PARK7 to be secreted
      across the plasma membrane have remained unclear. In the present study, we found
      that PARK7 secretion was increased by treatment with 6-OHDA via the
      unconventional secretory pathway in human neuroblastoma SH-SY5Y cells and MEF
      cells. We also found that 6-OHDA-induced PARK7 secretion was suppressed in Atg5-,
      Atg9-, or Atg16l1-deficient MEF cells or ATG16L1 knockdown SH-SY5Y cells,
      indicating that the autophagy-based unconventional secretory pathway is involved
      in PARK7 secretion. We moreover observed that 6-OHDA-derived electrophilic
      quinone induced oxidative stress as indicated by a decrease in glutathione
      levels, and that this was suppressed by pretreatment with antioxidant NAC. We
      further found that NAC treatment suppressed autophagy and PARK7 secretion. We
      also observed that 6-OHDA-induced autophagy was associated with activation of
      AMPK and ULK1 via a pathway which was independent of MTOR. Collectively these
      results suggest that electrophilic 6-OHDA quinone enhances oxidative stress, and
      that this is followed by AMPK-ULK1 pathway activation and induction of secretory
      autophagy to produce unconventional secretion of PARK7. ABBREVIATIONS: 6-OHDA: 6
      hydroxydopamine; AMPK: AMP-activated protein kinase; ATG: autophagy related;
      CAV1: caveolin 1; ER: endoplasmic reticulum; FN1: fibronectin 1; GSH:
      glutathione; IDE: insulin degrading enzyme; IL: interleukin; LDH: lactate
      dehydrogenase; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3
      beta; MEF: mouse embryonic fibroblast; MTOR: mechanistic target of rapamycin
      kinase; NAC: N-acetyl-L-cysteine; PARK7/DJ-1: Parkinsonism associated deglycase;
      PD: Parkinson disease; RPS6KB1/p70S6K: ribosomal protein S6 kinase B1; RPN1:
      ribophorin I; ROS: reactive oxygen species; ULK1: unc-51 like autophagy
      activating kinase 1; WT: wild-type.

PMID- 30112969
TI  - Preventing Child Sexual Abuse: Screening for Hidden Child Molesters Seeking Jobs
      in Organizations That Care for Children.
AB  - Approximately 10% of children and adolescents are sexually abused by adults
      caring for them outside the home. The current study tested the validity and
      reliability of a child protection screen to identify job applicants who pose a
      sexual risk to children. The screen uses three separate measures. In combination,
      they attempt to identify two types of sexually problematic job applicants: hidden
      abusers and people with cognitive distortions that encourage child sexual
      boundary violations by themselves or tolerate them by others. The high
      specificity (97.8% for males and 98.7% for females) favored the high number of
      job applicants and volunteers who have not crossed sexual boundaries with
      children. The study included over 19,000 participants, and the screen correctly
      identified 77% of the men and over 72% of the women who posed a sexual risk. The
      test-retest correlation was statistically significant at r(121) = .83, and the
      screening methodology is valid and reliable. By identifying most of the job
      applicants who are hiding their history of sexually abusing a child or hiding
      their belief that adult-child sex causes no harm from the organizations they are
      attempting to join, this new preemployment screen methodology can help child
      centered organizations protect children and adolescents in their care.

PMID- 30112971
TI  - Galphaq and hyper-phosphorylated ERK expression in Sturge-Weber syndrome
      leptomeningeal blood vessel endothelial cells.

PMID- 30112972
TI  - A report from the 8th Kuopio Alzheimer Symposium.
AB  - The international Kuopio Alzheimer Symposium was organized by the University of
      Eastern Finland in Kuopio, Finland on June 6-8, 2018 for the 8th time.
      Approximately 300 researchers in the fields of neuroscience and neurology from 12
      different countries around the world gathered to Kuopio to hear and discuss about
      the latest insights into the mechanisms and comorbidities and novel approaches
      for diagnosis, prediction, prevention and therapies of Alzheimer's disease and
      other neurodegenerative diseases. The 2-day international program on June 7-8
      included a keynote session, five oral scientific sessions and a poster session.
      The international symposium was preceded by a 'Memory Day' on June 6, held in
      Finnish and targeted to Finnish healthcare professionals, including doctors,
      psychologists and nurses, who work daily with patients suffering from
      neurodegenerative diseases.

PMID- 30112970
TI  - Highly specific host-pathogen interactions influence Metarhizium brunneum
      blastospore virulence against Culex quinquefasciatus larvae.
AB  - Entomopathogenic fungi are potential biological control agents of mosquitoes. Our
      group observed that not all mosquitoes were equally susceptible to fungal
      infection and observed significant differences in virulence of different spore
      types. Conidiospores and blastospores were tested against Culex quinquefasciatus
      larvae. Blastospores are normally considered more virulent than conidia as they
      form germ tubes and penetrate the host integument more rapidly than conidia.
      However, when tested against Cx. quinquefasciatus, blastospores were less
      virulent than conidia. This host-fungus interaction was studied by optical,
      electron and atomic force microscopy (AFM). Furthermore, host immune responses
      and specific gene expression were investigated. Metarhizium brunneum (formerly M.
      anisopliae) ARSEF 4556 blastospores did not readily adhere to Culex larval
      integument and the main route of infection was through the gut. Adhesion forces
      between blastospores and Culex cuticle were significantly lower than for other
      insects. Larvae challenged with blastospores showed enhanced immune responses,
      with increased levels of phenoloxidase, glutathione-S-transferase, esterase,
      superoxide dismutase and lipid peroxidase activity. Interestingly, M. brunneum
      pathogenicity/stress-related genes were all down-regulated in blastospores
      exposed to Culex. Conversely, when conidia were exposed to Culex, the
      pathogenicity genes involved in adhesion or cuticle degradation were up
      regulated. Delayed host mortality following blastospore infection of Culex was
      probably due to lower adhesion rates of blastospores to the cuticle and enhanced
      host immune responses deployed to counter infection. The results here show that
      subtle differences in host-pathogen interactions can be responsible for
      significant changes in virulence when comparing mosquito species, having
      important consequences for biological control strategies and the understanding of
      pathogenicity processes.

PMID- 30112973
TI  - Gendered Vulnerabilities in Times of Natural Disasters: Male-to-Female Violence
      in the Philippines in the Aftermath of Super Typhoon Haiyan.
AB  - The precarious situation faced by women and girls in the wake of climate-related
      disasters is illustrated through fieldwork conducted in Eastern Visayas in the
      Philippines, one of the regions most affected by Super Typhoon Haiyan in 2013.
      However, this article illustrates that these heightened levels of gendered
      violence faced by women and girls are not a result of the disaster alone; rather,
      they are rooted in the inequalities inherent in the social construction of gender
      prior to the catastrophe, which then become sharpened as efforts to survive
      become more urgent.

PMID- 30112974
TI  - Characterising model dynamics using sparse grid interpolation: Parameter
      estimation of cholera.
AB  - Sparse grid interpolation is a popular numerical discretization technique for the
      treatment of high dimensional, multivariate problems. We consider the case of
      using time-series data to calibrate epidemiological models from both
      phenomenological and mechanistic perspectives using this computational tool. By
      capturing the dynamics underlying both global and local spaces, our algorithm
      identifies potentially optimal regions of the parameter space and directs
      computational effort towards resolving the dynamics and resulting fits of these
      regions. We demonstrate how sparse grid interpolants can be effectively deployed
      to fit available data and discriminate between competing hypotheses to explain
      the current cholera epidemic in Yemen.

PMID- 30112975
TI  - Left ventricular unloading during veno-arterial ECMO: a review of percutaneous
      and surgical unloading interventions.
AB  - Short-term mechanical support by veno-arterial extracorporeal membrane
      oxygenation (VA ECMO) is more and more applied in patients with severe
      cardiogenic shock. A major shortcoming of VA ECMO is its variable, but inherent
      increase of left ventricular (LV) mechanical load, which may aggravate pulmonary
      edema and hamper cardiac recovery. In order to mitigate these negative sequelae
      of VA ECMO, different adjunct LV unloading interventions have gained a broad
      interest in recent years. Here, we review the whole spectrum of percutaneous and
      surgical techniques combined with VA ECMO reported to date.

PMID- 30112976
TI  - Economic analysis and life cycle impact assessment of municipal solid waste (MSW)
      disposal: A case study of Mumbai, India.
AB  - Municipal solid waste (MSW) management is a major concern in Indian cities. This
      work rigorously assesses the relative costs and the environmental and health
      benefits of alternative MSW management methods. Management of MSW over the next
      20 years for the city of Greater Mumbai was considered. A generic model was
      developed to determine the costs for (i) dumping on open ground, (ii) sanitary
      landfill without leachate treatment, (iii) landfilling with leachate treatment
      and (iv) regional composting and landfilling. LandGEM was used to quantify the
      gaseous emissions from landfill, while emissions from leachate and composting
      were taken from literature. The life cycle impact model of one tonne of MSW was
      developed using OpenLCA software and the International Reference Life Cycle Data
      System (ILCD) 2011 method was used for impact assessment. The cost of disposal of
      one tonne of waste was found to be INR344 (US$5.17), INR741 (US$11.13) and
      INR1367 (US$20.53), respectively, for the first three scenarios. As compared to
      open dumping, landfill gas flaring reduced the global warming potential by 32%
      and leachate treatment reduced freshwater ecotoxicity and total human toxicity
      marginally, by 20% and 60%, respectively. Composting-landfilling was the most
      preferred option, with a cost of INR531 tonne-1 (US$7.97), leading to a reduction
      in global warming potential by 79% and a slight decrease in freshwater
      ecotoxicity by 64%. Further, emissions due to accidental fires were also
      quantified. The study provides valuable insights for the selection of MSW
      management options for large metropolitan cities in developing countries.

PMID- 30112978
TI  - Exaggerated reaction to novelty as a predictor of incipient cognitive decline
      among community-dwelling older adults.
AB  - OBJECTIVE: The ability to detect covert markers of incipient cognitive decline
      among older adults before cognitive decline becomes overtly evident on
      traditional cognitive tests represents an important topic of research.
      Exaggerated reactions to novelty, reflected in novelty-induced increases in
      action planning latencies ("novelty effect"; NE) and low openness to experience
      (openness), have been previously associated with incipient cognitive decline
      among older adults who appeared cognitively normal at baseline. The purposes of
      the present study were to extend prior research on the utility of these markers
      by examining whether (a) NE and openness each predict cognitive change uniquely,
      and (b) whether these indices predict cognitive change above and beyond measures
      of memory, executive functions, processing speed/efficiency, premorbid IQ, and
      depressive symptoms. METHOD: Sixty-one cognitively normal community-dwelling
      older adults were administered a battery of tests assessing the relevant
      constructs at baseline and one-year follow up. Changes in cognitive status were
      assessed using the Demetia Rating Scale, 2nd Edition, NE was assessed using the
      Push-Turn-Taptap task (an electronic motor sequence learning task), and openness
      using the NEO Personality Inventory-Revised. The Test of Premorbid Functioning,
      and subtests from Repeatable Battery for the Assessment of Neuropsychological
      Status, Delis-Kaplan Executive Function System, and Wechsler Adult Intelligence
      Scale, 4th Edition, were used for additional assessment of baseline cognition.
      Depressive symptoms were assessed using the Geriatric Depression Scale. RESULTS:
      Results confirmed our hypothesis that both NE and openness contribute to
      prediction of cognitive change beyond baseline cognition and depressive symptoms,
      but none of the covariates (i.e., depression, executive functions, processing
      efficiency, or memory) themselves contributed to the model. NE and openness each
      contributed unique variance and were independent of each other. CONCLUSIONS:
      Openness and NE have the potential to provide evidence-based methods for
      estimating risk of future cognitive change in persons with currently normal
      standardized test scores.

PMID- 30112977
TI  - Source analysis of municipal solid waste in a mega-city (Guangzhou): Challenges
      or opportunities?
AB  - Rapid economic development accelerates the generation of municipal solid waste
      (MSW), and thereby calls for an effective and reliable waste management strategy.
      In the present work, we systematically investigated the status of MSW management
      in a mega-city of China (Guangzhou). The data were collected from literatures,
      government statistics and field sampling work. It can be found that a combination
      of waste sorting by individual residents and a necessary quantity of sanitation
      workers is one of the most feasible strategies to achieve a sustainable waste
      management. With implementation of that integrated strategy, approximately 0.03
      million tons of metal, 0.24 million tons of paper, as well as 0.46 million tons
      of plastics can be recycled/recovered for further processing. A cost reduction of
      70 million US$ is achieved in comparison with the un-optimized system due to the
      sale revenue of recyclable materials and the saving from waste disposal fees. The
      values of environmental assessment were expressed as environmental load units.
      The developed scenarios could decrease the environmental cost, namely, 0.66
      million US$. Based on the studies, waste sorting is urgently needed in Guangzhou.
      However, to make the proposed strategy to be more economically feasible, the
      sorting should be performed individually as well as with public participation.
      The establishment of a win-win situation for all stakeholders is an effective
      path for the improvement of the integrated waste management system.

PMID- 30112980
TI  - Experiences of lower limb prosthetic users in a rural setting in the Mpumalanga
      Province, South Africa.
AB  - BACKGROUND: Ambulation with a prosthesis is the ultimate goal of rehabilitation
      for a person with a major lower limb amputation. Due to challenges with
      prosthetic service delivery in rural settings, many patients with amputations are
      not benefitting from prosthetic interventions. Inaccessibility to prosthetic
      services results in worse functional outcomes and quality of life. Learning from
      the experiences of current prosthetic users in this setting can assist to improve
      prosthetic service delivery. OBJECTIVES: To explore the experiences of lower limb
      prosthetic users and to understand the importance of a lower limb prosthesis to a
      prosthetic user in a rural area of South Africa. STUDY DESIGN: A generic
      qualitative approach and an explorative design were utilised in this study.
      METHODS: A semi-structured interview guide was used to collect data from nine
      prosthetic users in a rural area in the Mpumalanga province of South Africa.
      Interviews were audio-recorded, transcribed verbatim and analysed thematically.
      Demographic details and information related to acute in-patient rehabilitation
      were analysed descriptively. RESULTS: All participants were independent in
      activities of daily living with their prosthesis and participated actively in
      their community. Participants reported that their prosthesis was essential to
      their functioning. High travel cost was highlighted as a barrier to the
      maintenance of their prosthesis. Patients were dissatisfied with being
      unemployed. CONCLUSION: Prosthetic intervention positively influences function,
      independence and community participation. Challenges relating to the
      accessibility, cost and maintenance of prosthetics should be a priority to ensure
      continued functional independence for prosthetic users. Clinical relevance
      Understanding the importance of a prosthesis to a prosthetic user validates
      prosthetic intervention for persons living with an amputation in a rural setting
      and is vital in establishing and remodelling effective systems for prosthetic
      service delivery.

PMID- 30112979
TI  - Mobility, prosthesis use and health-related quality of life of bilateral lower
      limb amputees from the 2008 Sichuan earthquake.
AB  - BACKGROUND: The 2008 Sichuan Earthquake resulted in many amputees, yet due to the
      rare incidence, few studies have explored the rehabilitation outcomes and quality
      of life of bilateral lower limb amputees after major natural disasters.
      OBJECTIVES: To evaluate rehabilitation outcomes of 17 young and adult bilateral
      lower limb amputees under the StandTall rehabilitation programme and to identify
      factors associated with successful functional recovery of bilateral amputees
      after large-scale disasters. STUDY DESIGN: Cross-sectional study. METHODS:
      Mobility (amputee mobility predictor), prosthesis use (Houghton Scale) and health
      related quality of life (Trinity Amputation and Prosthesis Experience Scale,
      Short Form 12) were evaluated through questionnaires and performance-based
      assessments. Means of scores were compared using T-tests. RESULTS: Subjects with
      bilateral through-knee or transtibial amputations had less activity restriction (
      p < 0.01) and higher mobility ( p = 0.03). Subjects using prostheses more than
      50% waking time had better general adjustment ( p = 0.02) and less functional
      restriction ( p = 0.01). Exercise and education were associated with higher
      mobility ( p = 0.06) and mental quality of life, respectively ( p = 0.09).
      CONCLUSIONS: Amputation level and knee joint salvage, prosthesis use, exercise
      and education were associated with better rehabilitation outcomes including
      ambulation, adjustment and quality of life in bilateral lower limb amputees from
      the 2008 Sichuan Earthquake. Clinical relevance The study examined a unique group
      of traumatic bilateral lower limb amputees who were young and healthy before
      having traumatic amputations from a single episode of natural disaster. The
      factors associated with better functional recovery after the earthquake were
      investigated and may support future development of post-disaster rehabilitation
      strategies for bilateral lower limb amputees.

PMID- 30112981
TI  - UK trial of the Osseointegrated Prosthesis for the Rehabilitation for Amputees:
      1995-2018.
AB  - BACKGROUND: Amputation of a limb impacts on patients' self-perception and quality
      of life. Prostheses directly anchored to the skeleton are being investigated,
      aiming to avoid soft tissue complications. OBJECTIVES: We report outcome data for
      the UK trial of the Osseointegrated Prosthesis for the Rehabilitation of Amputees
      Implant System with a minimum of 9-year follow-up. METHODS: Eighteen transfemoral
      amputees received unilateral implants between 1997 and 2008. Five were implanted
      before a formalised protocol, called Osseointegrated Prosthesis for the
      Rehabilitation of Amputees, was developed. Mean follow-up of the Pre
      Osseointegrated Prosthesis for the Rehabilitation of Amputees group is 11.4 years
      (1.8-18.6 years), while for the Post-Osseointegrated Prosthesis for the
      Rehabilitation of Amputees group it is 12.3 years (2.9-15.9). RESULTS: The Kaplan
      Meier cumulative survivorship is 40% for the Pre-Osseointegrated Prosthesis for
      the Rehabilitation of Amputees group and 80.21% for the Post-Osseointegrated
      Prosthesis for the Rehabilitation of Amputees group. Five implants (28%) have
      been removed, three (17%) for deep infection, one (5.6%) for chronic pain, later
      proven to be infected and one (5.6%) due to implant fracture secondary to
      loosening due to infection. Two patients (11%) have peri-implant infections
      suppressed with oral antibiotics. Eleven cases (61%) of superficial infection
      were successfully treated with antibiotics. 36-Item short-form health survey and
      Questionnaire for persons with a Transfemoral Amputation showed significant
      improvements in quality of life up to 5 years after implantation. CONCLUSION:
      This small cohort of patients demonstrates osseointegrated prosthesis allows
      prolonged usage and improves patients' quality of life compared to conventional
      prostheses. Clinical relevance These prostheses may provide a future gold
      standard for amputees and this study provides the first outcome data over such a
      time period to be reported from outside of the developers group.

PMID- 30112982
TI  - Gait speed as an indicator of prosthetic walking potential following lower limb
      amputation.
AB  - BACKGROUND: The relationship between gait speed and prosthetic potential (K-level
      classifications) and function has not been explored among people transitioning
      from hospital rehabilitation to the community. OBJECTIVES: To examine gait speed
      at discharge from inpatient rehabilitation among people prescribed a prosthetic
      leg after unilateral lower limb amputation, and associations between gait speed,
      prosthetic potential and functional ability. STUDY DESIGN: Cohort. METHODS: Gait
      speed (10-m walk test), K-level (Amputee Mobility Predictor) and Functional
      Independence Measure motor were compared for 110 people (mean (standard
      deviation) age: 63 (13) years, 77% male, 71% transtibial amputation, 70%
      dysvascular causes). RESULTS: Median (interquartile range) gait speed and
      Functional Independence Measure motor were 0.52 (0.37-0.67) m/s and 84 (81, 85),
      respectively. Median (IQR) gait speed scores for each K-level were as follows: K1
      = 0.17 (0.15-0.19) m/s, K2 = 0.38 (0.25-0.54) m/s, K3 = 0.63 (0.50-0.71) m/s and
      K4 = 1.06 (0.95-1.18) m/s. Median (IQR) FIM-Motor scores for each K-level were as
      follows: K1 = 82 (69-84), K2 = 83 (79-84), K3 = 85 (83-87) and K4 = 87 (86-89).
      Faster gait speed was associated with higher K-level, higher FIM-Motor, being
      younger, male and having transtibial amputation with nonvascular aetiology.
      CONCLUSION: Gait speed was faster among each higher K-level classification.
      However, gait speeds observed across all K-levels were slower than healthy
      populations, consistent with values indicating high risk of morbidity and
      mortality. Clinical relevance Factors associated with faster gait speed are
      useful for clinical teams considering walking potential of people with lower limb
      prostheses and those seeking to refine prosthetic rehabilitation programmes.

PMID- 30112983
TI  - Upper body accelerations during level walking in transtibial amputees.
AB  - BACKGROUND: The observation of upper body movement is gaining interest in the
      gait analysis community. Recent studies involved the use of body-worn motion
      sensors, allowing translation of laboratory measurements to real-life settings in
      the context of patient monitoring and fall prevention. OBJECTIVES: It was shown
      that amputee persons demonstrate altered acceleration patterns due to the
      presence of prosthetic components, while no information is available on how
      accelerations propagate upwards to the head during level walking. This
      descriptive study aims to fill this gap. STUDY DESIGN: Original research report.
      METHODS: Twenty definitive prosthesis users with transtibial amputation and 20
      age-matched able-bodied individuals participated in the study. Three magneto
      inertial measurement units were placed at head, sternum and pelvis level to
      assess acceleration root mean square. Three repetitions of the 10-m walking test
      were performed at a self-selected speed. RESULTS: Acceleration root mean square
      was significantly larger at pelvis and head level in individuals with amputation
      than in able-bodied participants, mainly in the transverse plane ( p < 0.05).
      Differences were also observed in how accelerations propagate upwards,
      highlighting that a different motor strategy is adopted in amputee persons gait
      to compensate for increased instability. CONCLUSION: The obtained parameters
      allow an objective mobility assessment of amputee persons that can integrate with
      the traditional clinical approach. Clinical relevance Transtibial amputees
      exhibit asymmetries due to the sound limb's support prevalence during gait: this
      is evidenced by amplified accelerations on the transverse plane and by related
      differences in upper body movement control. Assessing these accelerations and
      their attenuations upwards may be helpful to understand amputee's motor
      strategies and to improve prosthetic training.

PMID- 30112984
TI  - Factors associated with committed participation in a wellness-walking program for
      people with lower limb loss: A prospective cohort study.
AB  - BACKGROUND: Wellness activities can benefit health, yet committed adherence is
      challenging. OBJECTIVES: Identify factors associated with committed participation
      in an amputee wellness-walking program and determine benefits of committed
      participation. STUDY DESIGN: Prospective longitudinal cohort. METHODS: Two former
      Paralympians led the wellness-walking sessions. Participants provided medical
      history and self-reported balance confidence and prosthetic functional measures.
      Physiotherapy professionals/paraprofessionals assessed balance and gait.
      Committed participants-those attending three sessions within 3 years-were
      compared to one-time-only participants using Fisher's exact and independent t
      tests. First and third sessions for committed participants were compared with t
      tests. A bootstrapped multivariable logistic regression model was developed using
      significant univariate predictors. RESULTS: A total of 305 volunteers averaged
      55.7 +/- 15.2 years, including 68.4% men, 78.4% White race; 51.8% with
      dysvascular amputations, 40.5% with ?1 prosthetic knee; and 49.1% independent
      community walkers. Committed participants were initially similar to one-time-only
      participants ( p > 0.05) except for fewer years since amputation ( p = 0.007),
      better balance ability ( p = 0.001), and greater likelihood of dieting ( p =
      0.030). The final model-balance ability (odds ratio = 2.4), dieting (odds ratio =
      3.3), and years since amputation (odds ratio = 0.94)-identified 88.0% of
      committed participants ( p = 0.007). Balance confidence and functional
      improvements after three sessions were not significant ( p > 0.07). CONCLUSION:
      Committed participants were more likely to diet, have better balance ability, and
      have more recent amputations than one-time-only participants. Clinical relevance
      Knowing which characteristics identify people most likely to become committed
      participants-such as people with recent amputations, an interest in dieting, and
      better balance ability-may help health practitioners from different professions
      promote consistent participation in wellness activities that may benefit self
      reported function.

PMID- 30112985
TI  - Effects of Human Full-length Amelogenin and C-terminal Amelogenin Peptide on the
      Proliferation of Human Mesenchymal Stem Cells Derived from Adipose Tissue.
AB  - Amelogenins are enamel matrix proteins that play crucial roles in enamel
      formation. Previous studies have indicated that amelogenin and amelogenin C
      terminal peptides have cell-signaling functions. Recently, adipocyte-derived
      mesenchymal stem cells (ADSCs) have received attention as a potential source of
      stem cells for use in regeneration therapy. In this study, we examined the
      effects of human full-length amelogenin (rh174) and amelogenin C-terminal peptide
      (amgCP) on the proliferation of ADSCs. ADSCs were cultured in the presence of
      amgCP or rh174. Cell proliferation was analyzed using BrdU immunoassay and MTS
      assay. Cell migration was evaluated by ELISA. The MAPK-ERK pathway was examined
      by phospho-p44/42 MAPK (Thr202/Tyr204) sandwich ELISA and western blotting. A
      specific MAPK inhibitor, U0126, was used to block ERK activity. ADSC
      proliferation and migration were significantly (P < 0.05) increased in the
      presence of rh174 or amgCP compared to non-treated control cells. The increased
      proliferation of ADSCs induced by rh174 or amgCP was significantly (P < 0.05)
      inhibited in the presence of 2 ug/ml U0126. The pERK/tERK ratio was significantly
      (P < 0.05) increased upon treatment with rh174 or amgCP compared to non-treated
      ADSCs, while this increase was significantly (P < 0.05) suppressed by the
      addition of U0126. Similar results were found by western blot analysis. In
      conclusion, amgCP and rh174 increase ADSC proliferation via the MAPK-ERK
      signaling pathway, and ADSCs may be useful for tissue regeneration in the
      orofacial region.

PMID- 30112986
TI  - Preclinical Pharmacokinetics of Triptolide: A Potential Antitumor Drug.
AB  - Triptolide, a bioactive component in Tripterygium wilfordii extracts, possess
      strong anti-proliferative activity on all 60-national cancer institute (NCI)
      cancer cell lines. The antitumor property of triptolide has made it become a
      promising anti-cancer drug. However, the widespread use of triptolide in the
      clinical practice is greatly limited for its multi-organ toxicity and narrow
      therapeutic window. All the toxic characteristics of triptolide are associated
      with the pharmacokinetics especially its distribution and accumulation in the
      target organ. The article presents a comprehensive review of the preclinical
      pharmacokinetics of triptolide. Oral triptolide is rapidly and highly absorbed.
      Grapefruit juice affects oral absorption, increasing the area under the
      concentration-time curve (AUC) by 153 % and the maximum concentration (Cmax) by
      141 %. The AUC and the Cmax are not dose proportional. Triptolide distributes
      into the liver, heart, spleen, lung and kidney. Biotransformation of triptolide
      in rats includes hydroxylation, sulfate, glucuronide, N-acetylcysteine (NAC) and
      glutathione (GSH) conjugation and combinations of these pathways. Less than 4 %
      of triptolide was recovered from the feces, bile and urine within 24 h. After
      repeating dosage, triptolide was eliminated quickly without accumulation in vivo.
      As a substrate of P-glycoprotein (P-gp) and CYP3A4, triptolide could have
      clinically significant pharmacokinetic interactions with those proteins
      substrates/inhibitors.

PMID- 30112987
TI  - Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, reality or
      dream in managing patients with cardiovascular disease.
AB  - Statins have been a major keystone in the management of patients with
      atherosclerotic cardiovascular disease. The benefits of inhibiting HMG CoA
      reductase, via statins, were translated into reduction in LDL-c (cholesterol)
      with proportionate decrease in cardiovascular events in response to the magnitude
      of LDL-c reduction. Despite major advances in pharmacological treatments,
      including the use of high-dose statins, there are urgent need to further reduce
      future cardiovascular risk. This is in particularly important since 1 out of 5
      high-risk atherosclerotic patients who achieve low LDL-c return with a second
      cardiovascular event within five years. Although this residual risk post-statin
      is largely heterogeneous, lowering LDL-c beyond 'normal' or guidelines
      recommended level of LDL-c using novel therapies has resulted in further
      reduction in cardiovascular events. PCSK9 inhibitors are a new class of lipid
      lowering drugs that are either fully human monoclonal antibodies (evolocumab and
      alirocumab) or humanised monoclonal antibodies (bococizumab) that effectively
      reduce LDL-c to unprecedented level. By blocking circulating PCSK9, these drugs
      would preserve LDL receptors and prevent them from cellular degradation. This
      process promotes recycling of LDL receptors back to hepatocytes surface, leading
      into further reduction of LDL-c. Combining PCSK9 inhibitors with statin have led
      into lower LDL-c, reduction in plaque volume and more importantly reduction in
      future cardiovascular events. While these drugs are very promising, the
      unselective approach of applying these monoclonal antibodies may not prove to be
      cost-effective and potentially exposing some patients to unnecessary side
      effects. The current review will discuss the use of PCSK9 inhibitors in patients
      with atherosclerotic disease.

PMID- 30112988
TI  - The Impact of Antiepileptic Drugs on Vitamin Levels in Epileptic Patients.
AB  - BACKGROUND: The impact of antiepileptics on serum vitamin levels is controversial
      and uncertain. With no clear conclusions on the impact of antiepileptics on serum
      levels of vitamins, there is a need for further clinical studies in order to
      ascertain the impact of old and newer antiepileptic drugs on serum levels of
      vitamins in epileptic patients, thus accomplishing a suitable usage of vitamins
      supplementation. OBJECTIVE: The intention of the present research is to confirm
      the hypothesis of whether or not vitamin levels are altered with antiepileptic
      drugs. The study also aims to reveal which vitamin levels are particularly more
      altered, are vitamin levels affected by gender and the type and number of
      antiepileptics used. METHODS: The present research was piloted in collaboration
      with the Department of Neurology in Qilu Hospital of Shandong University. A total
      of 63 serum samples of epileptic patients receiving antiepileptics as monotherapy
      or polytherapy were requested for analysis of nine vitamin serum levels. Total
      nine vitamins (B1, B2, B6, B9, B12, A, C, D and E) in epileptic patients
      receiving antiepileptic drugs were analyzed. The serum results of all vitamins
      were compiled and evaluated with SPSS. RESULTS: It was alarmingly found that
      serum levels of vitamin D were particularly very low in almost all (90%)
      epileptic patients in this study. Notably, serum levels of vitamin C and vitamin
      B1 were also below reference range in 72% and 46% epileptic patients,
      respectively. The remaining vitamins were almost in reference range for most of
      the patients. In our study, mean and frequency of vitamin D, C and B1 levels do
      not vary too much among different gender groups. The patients receiving newer
      antiepileptic drugs displayed a slightly increased serum vitamin D levels in
      comparison to the patients receiving older antiepileptic drugs. We found low
      vitamin D, C and B1 serum levels in patients who were on monotherapy as in
      comparison with patients on polytherapy. CONCLUSION: The most significant and
      surprising finding of this study revealed that serum vitamin D levels in
      particular were very low in almost all patients and in some patients' vitamin B1
      serum levels were also below the reference range. More importantly, it is first
      time reported here that vitamin C serum levels were also below reference range in
      the majority of these Chinese epileptic patients. It is recommended that all
      these vitamins should be regularly monitored in addition to therapeutic drug
      monitoring of antiepileptic drugs. Additional clinical trials are required for
      further evaluation. It is also recommended that epileptic patients with low serum
      levels of these vitamins may be prescribed vitamins supplementations with
      antiepileptic drugs in order to control their seizures more effectively and
      efficiently.

PMID- 30112989
TI  - Regenerative Dentistry and Stem Cells: A Multilineage Differentiation as a Safe
      and Useful Alternative Way of Harvesting and Selection Adipose Derived
      Mesenchymal Stem Cells.
AB  - BACKGROUND: This review aims to address procedures and indications for the
      application of the adipose-derived stem cells (ADSCs) for regenerative dentistry.
      ADSCs have rarely been used in this particular field; conversely, experience from
      other clinical fields and basic research seems to recommend the suitability of
      this application. AIMS AND METHODS: We reviewed 32 out of 193 articles on Medline
      sorted by the relevance option. The main purpose of this paper is to perform a
      short review of the application of stem cells in regenerative dentistry,
      describing a multilineage differentiation as a safe and useful alternative way of
      harvesting and selection of ADSCs. RESULTS AND CONCLUSION: The most common
      derivation of stem cells for regenerative dentistry is from the adipose tissue.
      There are conditions in which the levy adipose cannot be easily achieved, or
      where large amount of grafting is not needed. For this purpose, the possibility
      of selecting stromal stem cells directly from the lax subcutaneous connective
      tissue, preferably of the head region, would allow a technical simplification.

PMID- 30112990
TI  - Nitrite-stimulated gastric formation of S-nitrosothiols as an antihypertensive
      therapeutic strategy.
AB  - Hypertension is usually associated with deficient nitric oxide (NO)
      bioavailability, and therefore stimulating NO activity is an important
      antihypertensive strategy. Recently, many studies have shown that both nitrite
      and nitrate anions are not simple products of NO metabolism and indeed may be
      reduced back to NO. While enzymes with nitrite-reductase activity capable of
      generating NO from nitrite may contribute to antihypertensive effects of nitrite,
      another mechanism involving the generation of NO-related species in the stomach
      from nitrite has been validated. Under acidic conditions of the stomach, nitrite
      generates NO-related species that form S-nitrosothiols. Conversely, drugs that
      increase gastric pH may impair the gastric formation of S-nitrosothiols, which
      may mediate antihypertensive effects of oral nitrite or nitrate. Therefore, it is
      now becoming clear that promoting gastric formation of S-nitrosothiols may result
      in effective antihypertensive responses, and this mechanism opens a window of
      opportunity in the therapy of hypertension. In this review we discuss the recent
      studies supporting the gastric generation of S-nitrosothiols as a potential
      antihypertensive mechanism of oral nitrite. We also highlight some drugs that
      increase S-nitrosothiols bioavailability, which may also improve the responses to
      nitrite/nitrate therapy. This new approach may result in increased nitrosation of
      critical pharmacological receptors and enzymes involved in the pathogenesis of
      hypertension, which tend to respond less to their activators resulting in lower
      blood pressure.

PMID- 30112991
TI  - Novel Therapeutic Potential of Mitogen-Activated Protein Kinase Activated Protein
      Kinase 2 (MK2) in Chronic Airway Inflammatory Disorders.
AB  - OBJECTIVE: The primary focus of this review is to highlight the current and
      emerging pro-inflammatory role of MK2 kinase signaling in p38MAPK pathway and to
      provide a detailed evaluation on the prospects of MK2 inhibition with special
      emphasis on the etiology of chronic inflammatory airway diseases, such as asthma,
      idiopathic pulmonary fibrosis, lung cancer, acute lung injury and acute
      respiratory distress syndrome. BACKGROUND: Mitogen-activated protein kinase
      activated protein kinase 2 (MK2) is a serine-threonine kinase downstream to
      p38MAPK and is activated directly by stress and inflammatory signal through p38
      phosphorylation. MK2 is stimulated in a wide variety of inflammatory conditions,
      and has been shown to be a direct and essential component in regulating the
      biosynthesis of pro-inflammatory cytokines such as TNF-alpha, IL-6 and IL-1beta
      etc. Targeted disruption of MK2 leads to a significant reduction in the levels of
      these cytokines. Therefore, MK2 has been identified as an effective alternate
      strategy (alternative to p38) to block this pro-inflammatory pathway. RESULTS:
      The inhibition of MK2 may lead to similar or better efficacy as that of p38
      inhibitors, and interestingly avoids the systemic toxicity shown by the p38
      inhibitors. Thus, MK2 has been the focus of intense interdisciplinary research
      and its specific inhibition can be a novel and potential therapeutic strategy for
      treatment of chronic airway inflammatory diseases. CONCLUSION: Promising
      advancement in understanding and rigorous exploration on the role of MK2 kinase
      in inflammatory processes may contribute to the development of newer and safer
      therapy for the treatment of chronic airway inflammatory diseases in future.

PMID- 30112992
TI  - Structure, Function and Inhibition of Poly(ADP-ribose)polymerase, Member 14
      (PARP14).
AB  - Poly(ADP-ribose)polymerase, member 14 (PARP14, alternatively named ARTD8, BAL2,
      and COAST6) is an intracellular mono(ADP-ribosyl) transferase. PARP14 transfers a
      negatively charged ADP-ribose unit from a donor NAD+ molecule onto a target
      protein, post-translationally. PARP14's domain architecture consists of three
      macrodomains (Macro1, Macro2 and Macro3), a WWE domain and an ARTD (or catalytic
      domain). The Macro2 and Macro3 domains bind ADPribose (ADPr) with high affinity,
      whereas the WWE domain stabilizes the protein structure by binding to ADPr
      derivatives. The catalytic domain is involved in binding the NAD+ and catalyzing
      the mono- ADP-ribosylation reaction. PARP14 has been identified as a possible
      anti-cancer and antiinflammatory target. Acting as a transcriptional co-activator
      for STAT6, PARP14 acts to promote the over activation of the Th2 immune response,
      thus promoting the metabolic change to an anaerobic state (Warburg effect) and
      activation of cell survival pathways through JNK2 and the PGI/AMF complex. These
      changes are consistent with the metabolic sophistication observed in cancer, and
      the immune imbalance in inflammatory diseases. Current literature on selective
      and unselective PARP14 inhibitors are reviewed and discussed. Although there is
      no evidence that selective PARP inhibitors would be advantageous we have proposed
      some strategies for future design of selective PARP14 inhibitors.

PMID- 30112993
TI  - Benzamide and Benzamidine Compounds as New Inhibitors of Urokinasetype
      Plasminogen Activators.
AB  - BACKGROUND & METHOD: In this ongoing research, it is aimed to investigate the
      synthesis, structure identification and effects on urokinase-type plasminogen
      activators (uPA) and its receptor levels of 4-(3H-imidazo[4,5-b]pyridin-2-yl)-N
      substituted benzamide and benzamidine derivatives. uPA levels obtained from 4b
      and 7d administration were similar to 5-FU (5-fluorouracil) for colorectal
      carcinoma cells (p<0.05). 4b and 7d significantly reduced uPAR (urokinase-type
      plasminogen activator receptor) levels on both cell lines (p<0.05). CONCLUSION:
      uPAR levels obtaining from 4b and 7d administration were similar to 5-FU for both
      cell lines colorectal (Colo205, CCL-222) and hepatocellular (HepG2, CCL-23)
      carcinoma cells (p<0.05).

PMID- 30112994
TI  - A Review on Recent Synthetic Strategies and Pharmacological Importance of 1,3
      Thiazole Derivatives.
AB  - Thiazole is the versatile heterocyclic compound in heterocyclic chemistry and in
      drug design. Presence of several reaction sites in the thiazole moiety extends
      their range of applications and leads to new solutions for challenges in
      synthetic and medicinal chemistry. Thiazole derivatives are widely used as
      bioactive agents, liquid crystals, sensors, catalysts, etc. The motivating
      molecular architecture of 1,3-thiazoles make them suitable moieties for drug
      development. In this review, our aim is to corroborate the recent data available
      on various synthetic strategies and biological properties of 1,3-thiazole
      derivatives.

PMID- 30112995
TI  - Post chikungunya chronic arthritis: a systemic inflammatory status triggering the
      acute coronary syndrome.
AB  - BACKGROUND: Atherosclerosis and coronary plaque destabilization are linked to
      each other. Infections due to various microbes may trigger acute coronary
      syndrome (ACS) by systemic inflammation cascade. METHODS: We have evaluated the
      prevalence of Post chikungunya chronic arthritis (PCCA) among 400 consecutive ACS
      patients (Case group) and compared with control group subjected to elective
      surgery by the prospective case-control observational study. Cases were excluded
      if standard criteria of ACS were not satisfied and in control group if the
      patient suffered a myocardial infarction (MI) within 28 days of elective surgery.
      PCCA duration more than two years or serum IgM anti-CCP positive patients were
      also excluded from the case as well as a control group. RESULTS: The case and
      control groups were similar except, less number of heart failure (O.R.7.3, 95%
      C.I. 3.3-15.9) and higher past history of coronary artery disease patients (O.R.
      0.5, 95% C.I. 0.3-0.9) in the elective surgery (control) group. PCCA was present
      in 24 out of 400 ACS cases and 8 out of 400 control group. Among ACS case
      patients, those suffering from PCCA tended to be younger and more often women,
      with more diabetes, hypertension, chronic kidney injury and high mean CRP. In
      unadjusted analysis PCCA was three times more common in the case versus control
      (O.R. 3.0, 95% C.I. 1.4-6.4); results were indistinguishable after
      multidiscipline adjustment (O.R. 3.0, 95% C.I. 1.3-6.8). CONCLUSIONS: PCCA is
      common among patients with ACS and post-infective systemic inflammation of PCCA
      may trigger plaque destabilization.

PMID- 30112996
TI  - N-(Sulfamoylbenzoyl)-L-proline Derivatives as Potential Non-beta-lactam ESBL
      Inhibitors: Structure-Based Lead Identification, Medicinal Chemistry and
      Synergistic Antibacterial Activities.
AB  - BACKGROUND: There is an urgent need to develop novel inhibitors against
      clinically widespread extended-spectrum beta-lactamases (ESBLs) to meet the
      challenges of the ever-evolving threat of antibiotic resistances. Most existing
      ESBL inhibitors sharing a common chemical feature of beta-lactam ring in their
      molecule, this structural characteristic makes them intrinsically susceptible to
      enzymatic breakdown by the resistance mechanisms employed by the bacteria.
      OBJECTIVE: The aim of this study was to screen and discover novel lead compounds
      by using L-proline as initial scaffold to create a "non-sulfur, non-beta-lactam"
      new chemotypes for potential ESBL inhibitors. METHODS: Structure-based molecular
      docking and virtual screening were employed in the novel inhibitor generation
      process for lead compound screening and SAR analysis. Evaluation of the ESBL
      inhibitory activity of the lead compounds was performed in combination with three
      of the most susceptible antibiotics: ceftazidime, meropenem and ampicillin,
      against thirteen ESBL enzymes including four new CTX-M harboring strains and four
      KPC-2 producing species. RESULTS: L-proline derived (S)-1-(2
      sulfamoylbenzoyl)pyrrolidine-2-carboxylic acid (compound 6) as a "non-sulfur, non
      beta-lactam" and the most potential ESBL inhibitor was identified. Compound 6
      possesses ideal anti-resistance activities by reducing MICs of ceftazidime,
      meropenem and ampicillin by 16-133, 32-133 and 67-267 fold respectiveily. The
      inhibitory mechanism of 6 with CTX-M, KPC-2 and penicillinase were proposed and
      probed with molecular docking analysis. CONCLUSION: Given that the simple proline
      derivative but promising synergistic antibacterial properties of compound 6
      augers well for further investigations into its in vivo efficacy.

PMID- 30112997
TI  - Dabigatran Reversal with Idarucizumab in an Emergency Lumbar Puncture: a case
      report.
AB  - The widespread use of direct oral anticoagulants (DOACs) has been increasing the
      conditions in which emergency physicians are forced to rapidly reverse
      anticoagulation in case of life-threatening bleeding or need of urgent surgery or
      invasive procedures. Recent approval of Idarucizumab, a humanized monoclonal
      antibody fragment (Fab), offered the opportunity to rapidly and safely neutralize
      the anticoagulant effect of Dabigatran. However, real world experience of its
      effective use in different emergency setting is now required. Lumbar puncture
      (LP) is recognized as an invasive procedure at major bleeding risk and is
      therefore contraindicated in anti-coagulated patients. We report a successful use
      of Idarucizumab in an emergency LP of a young woman with a possible diagnosis of
      encephalitis and a previous history of venous thromboembolism on longterm
      treatment with Dabigatran 150 mg twice a day.

PMID- 30112998
TI  - Mesenchymal stem cells, immune cells and tumor cells cross talk: A sinister
      triangle in the tumor microenvironment.
AB  - Mesenchymal Stem Cells [MSCs] are a heterogeneous population of fibroblast-like
      cells which maintain self-renewability and pluripotency. Many studies have
      demonstrated the immunomodulatory effects of MSCs on the innate and adaptive
      immune cells. As a result of interactions with tumor cells, microenvironment and
      immune-stimulating milieu, MSCs contribute to tumor progression by several
      mechanisms, including sustained proliferative signal in cancer stem cells [CSCs],
      inhibition of tumor cell apoptosis, transition to tumor associated fibroblasts
      [TAFs], promotion of angiogenesis, stimulation of epithelial-mesenchymal
      transition [EMT], suppression of immune responses, and consequential promotion of
      tumor metastasis. Here we present an overview of the latest findings on Janus
      faced roles that MSCs play in tumor microenvironment [TME], with a concise focus
      on innate and adaptive immune responses.

PMID- 30112999
TI  - Recent advances of useful cell sources in the periodontal regeneration.
AB  - BACKGROUND: Periodontitis is an inflammatory disease that can result in
      destruction of the tooth attachment apparatus. Therefore, periodontal tissue
      regeneration is currently an important focus of research in the field. Approaches
      using stem cells and reprogrammed cells, such as induced pluripotent stem cells
      (iPSCs) or trans-differentiated cells, represent the cutting edge in periodontal
      regeneration, and have led to many trials for their clinical application.
      Objectives and Results: In this review, we consider all available stem cell
      sources, methods to obtain the cells, their capability to differentiate into the
      desired cells, and the extent of their utilization in periodontal regeneration.
      In addition, we introduce the new concepts of using iPSCs and trans
      differentiated cells for periodontal regeneration. Finally, we discuss the
      promise of tissue engineering for improving cell therapy outcomes for periodontal
      regeneration. CONCLUSIONS: Despite their limitations, iPSCs and trans
      differentiated cells may be promising cell sources for periodontal tissue
      regeneration. Further collaborative investigation is required for the effective
      and safe application of these cells in combination with tissue engineering
      elements, like scaffolds and biosignals.

PMID- 30113000
TI  - Modulation of Mitochondrial and Epigenetic Targets by Polyphenols-rich Extract
      from Araucaria angustifolia in Larynx Carcinoma.
AB  - Araucaria angustifolia extract (AAE) is a polyphenol-rich extract that has gained
      interest as a natural anticancer agent. Recent work suggests that AAE induces
      oxidative damage and apoptosis through its action on decreasing complex I
      activity of the mitochondrial electron transport chain (ETC). In the present
      study, we aimed to further examine the specific targets by which AAE exerts pro
      apoptotic effects in HEp-2 cancer cells. Specifically, the effect of AAE on the:
      1) levels of pyruvate dehydrogenase was assessed by ELISA assay; 2) levels of
      mitochondrial ETC complexes, focusing on complex I at the gene transcript and
      protein level relevant to ROS generation was evaluated by multiplex ELISA
      followed by qRT-PCR and immunoblotting; 3) mitochondrial membrane potential
      (DeltaPsim) was assessed by MitoTracker Red CMXRos; and 4) chemical variations on
      DNA was evaluated by dot-blotting in HEp-2 cells. Results demonstrated that AAE
      increased protein levels of PDH, switching energy metabolism to oxidative
      metabolism. Protein expression levels of complex I and III were found decreased
      in AAE-treated HEp-2 cells. Analyzing the subunits of complex I, changes in
      protein and gene transcript levels of NDUFS7 and NDUFV2 were found. AAE was able
      to induced a loss of DeltaPsim, along with DNA hypomethylation and decreased DNA
      (cytosine-5)-methyltransferase 1 activity. Our data demonstrate for the first
      time that AAE alters expression of NDUFS7 and NDUFV2 mitochondrial subunits and
      induce epigenetic changes in HEp-2 cancer cells leading to a possible suppression
      of oncogenes.

PMID- 30113002
TI  - Sofosbuvir: really meets the unmet needs for Hepatis C treatment ?
AB  - Chronic hepatitis C remains a major public health concern with a prevalence of
      more than 1% worldwide. Of late, with the discovery of newer drugs, chronic HCV
      treatment has touched new dimensions. The treatment has progressed from
      Interferons to pegylated interferon (Peg IFN) based therapy, with or without
      ribavirin to treatment with orally active direct acting antivirals (DAA) with Peg
      IFN and ribavirin and eventually to various combinations of DAA, without IFN.
      Introduction of newer DAAs has transfigured the treatment of chronic HCV. Chronic
      HCV patients with advanced liver disease, psychiatric condition, anemia or
      autoimmune diseases, not eligible for Peg IFN based therapy have a ray of hope
      now. Amongst all DAAs , nucleoside inhibitors have been the most promising agent.
      Thus the present review focuses on Sofosbuvir, one of the most effective
      nucleoside inhibitors; in terms of potency, resistance profile, activity against
      all genotypes of HCV and adverse effects. FDA approved Sofobuvir for clinical use
      in 2013. Chemically it is 2'-deoxy-2'-alpha-fluoro-beta-C-methyluridine-5'
      triphosphate; a phosphoramidate prodrug that is activated by enzyme present in
      human liver. It is a highly potent inhibitor of HCV NS5B polymerase. Efficacy of
      the Sofosbuvir has been established in various phase 2 and phase 3 clinical
      trials like PROTON, ELECTRON, FUSION, POSITRON etc. Sofosbuvir has a good safety
      profile with few mild to moderate adverse effects. Evidence reveals that
      sofosbuvir has substantial impact on the treatment of HCV.

PMID- 30113001
TI  - Bactericidal Activity of a Cationic Peptide on Neisseria meningitidis.
AB  - The increasing prevalence of antibiotic resistance has formed an urgent need for
      substitute drugs with new mechanisms of action. Antimicrobial peptides (AMPs) are
      promising candidates that could address the meal of multidrug-resistant bacteria.
      Neisseria meningitidis represents a pathogen of great public health importance in
      both developed and developing countries and is intrinsically highly resistant to
      some AMPs, such as polymyxin B. In this work, a cationic 11-residue peptide named
      of poly-Leu (KLKLLLLLKLK) was synthesized and its antimeningococcal activity
      availed and compared with cecropin A and the poly-P (KLKPPPPPKLK) by flow
      cytometry, electron microscopy and measurement of the periplasmatic enzyme
      alkaline phosphatase activity. Live N. meningitidis serotype B cells were grown
      with different concentrations of the peptides and after washing propidium iodide
      was added and the optical density measured at 600 nm. N. meningitidis cells
      containing 10 ug/106 cells of the poly-Leu peptide presented 90,3% uptake of the
      dye (EC50 value of 7.9 ug mL-1). The uptake of the dye by control cells not
      incubated with the poly-Leu peptide or with an identical concentration of
      cecropin and poly-Pro peptides was lesser than 10%. The susceptibility of the N.
      meningitidis serotype B to the cationic peptide poly-Leu was also demonstrated by
      electron microscopy analysis. The damage increased with the increase of the
      peptide concentration and a slicing and peels effect of the cellular wall and
      apparent injury of the internal membrane. The damage to the external membrane was
      confirmed through the measurement of the alkaline phosphatase.

PMID- 30113003
TI  - Evaluation of antibiotic susceptibility pattern and distribution of coa genes in
      coagulase negative S. aureus from Ahvaz, Iran.
AB  - BACKGROUND: Staphylococcus aureus is one of the important causes of clinical
      infections that can be more destructive by its antibiotic resistant strains.
      OBJECTIVE: This study aimed to determine the antibiotic susceptibility pattern
      and distribution of mecA and coa genes in clinical isolates of S. aureus.
      METHODS: Two hundred seventy-three specimens suspected to S. aureus were taken
      from hospitals of Ahvaz, southwest of Iran. Isolates were identified by standard
      microbiologic tests and confirmed by the molecular method. Antimicrobial
      susceptibility testing was carried out by disk diffusion method. The presence of
      mecA and coa genes were determined by PCR method. RESULTS: Of a total of 200
      isolates which were tested for coagulase tube test 143 (71.5%) were shown
      coagulase positive, and 57 (28.5%) were a coagulase-negative reaction.
      Antibacterial susceptibility pattern of 200 S. aureus isolates showed that the
      highest and lowest susceptibility rate to linezolid (98%) and ciprofloxacin
      (42%), respectively. The prevalence of methicillin-resistant S. aureus (MRSA) by
      detection of mecA gene were estimated 47.5 % (95/200), of which the rate of MRSA
      in coagulase positive and negative isolates were 35% (50/143), and 65% (45/57),
      respectively. Meanwhile, coa gene was detected in 100% of coagulase positive and
      28.1% of coagulase-negative isolates. CONCLUSION: The results of this study
      showed that the number of atypical CNSA in our area is high. Since the coagulase
      test is an essential test for diagnosis of S. aureus, our findings regarding the
      emergence of CNSA is a warning about the misdiagnosis and selection of
      appropriate treatment approach for S. aureus isolates.

PMID- 30113004
TI  - Prevalence of human and animal fascioliasis in Iran: Systematic Review and Meta
      analysis.
AB  - OBJECTIVE: The aim of this study was to investigate the prevalence of
      fascioliasis in humans, cattle, sheep, and goats,which was done by a systematic
      review in Iran. METHODS: Fifty articles were extracted from sites, including
      Iranian papers such as Google scholar, Magiran, IranMedex, SID, and Pubmed. Out
      of these, 21 articles were selected for meta-analysis. Essential information for
      meta-analysis was extracted from papers and archived inExcel software,for
      calculating bystatistical tests. Variance of each study was obtained using the
      binomial distribution. Heterogeneity of the studies was surveyed using I2 index.
      Data wasanalyzed using a random effect model. RESULTS: From the 21 collected
      papers, 1,275,506 samples from cow (507,152), sheep (454,882), goat (207,925),
      and human (105,547) had been surveyed in Iran. Eight studies were conducted on
      humans and 13 on animals. Prevalence rate obtained in humans was 3% with
      confidence interval (CI) of 95% (1%-7%). Prevalence rate obtained in cows, sheep,
      and goats was 13% with CI of 95% (10%-16%). The highest level of prevalence was
      reported from cities in the North in animals with a prevalence of 14%. Highest
      level of prevalence was reported from Gilan in humans with a prevalence of 0.1%.
      CONCLUSION: The prevalence of the disease in Iran has reduced in recent years,
      but this hasnot loweredthe importance of fascioliasis. In many cities of Iran
      there is no study on the disease.

PMID- 30113005
TI  - Autophagy and Mitochondria: Targets in Neurodegenerative Disorders.
AB  - BACKGROUND & OBJECTIVE: Cellular physiology and energy metabolism are maintained
      by the constant supply of energy furnished by the powerhouses of the cell called
      mitochondria. Cellular homeostasis depends on the timely clearance of damaged
      cellular organelles and proteins via pathways including autophagy. Mitochondria
      and mitochondrial autophagy play a vital role in cellular health and failure of
      these pathways can have a devastating effect on cellular homeostasis. Amongst the
      various cell types, neuronal cells are more vulnerable to bioenergetic depletion
      since most of their functions critically depend on the availability of energy
      derived from mitochondrial metabolism, thus making neurodegenerative disorders an
      obstinate issue. Research in the past few decades has shown that these
      neurodegenerative disorders are associated with mitochondrial dysfunction and
      compromised mitophagy leading to accumulation of protein aggregates which
      ultimately culminate in neurodegeneration. CONCLUSION: Thus, targeting
      mitochondria and autophagy-related proteins and enzymes in neurodegenerative
      disorders may open the avenues for potential targets for discovering effective
      therapies. Here, we review the involvement of mitochondrial and autophagy
      dysfunction in neurodegenerative disorders specifically focusing on Alzheimer's,
      Parkinson's and Huntington's disease.

PMID- 30113006
TI  - Bioinformatic Analysis Reveals Key Genes and Pathways in Aging Brain of
      Senescence-accelerated Mouse P8 (SAMP8).
AB  - BACKGROUND: Aging is a complex process accompanied with the decline of the
      different physiological functions. Numerous differentially expressed genes (DEGs)
      have been found in the aging brain of senescence-accelerated mouse P8 (SAMP8),
      however, it was challenging to screen out the crucial ones. OBJECTIVE: This study
      aimed to explore the crucial genes and pathways in aging brain of SAMP8 mice,
      which would be beneficial for understanding the pathogenesis of brain aging.
      METHODS: Firstly, 430 genes that are differentially expressed in SAMP8 mice
      versus SAMR1 mice were obtained from 9 gene expression studies, and gene-gene
      network was constructed. Clustering analysis and topological analysis were used
      to single out the hub genes from this network. Secondly, pathway enrichment
      analysis was utilized to identify the key pathways from the 430 DEGs, and the
      DEGs in key pathways were considered as functional genes. Thirdly, the inner
      network between hub genes and functional genes was constructed, and the key genes
      were predicted. Parts of the key genes were experimentally verified by
      quantitative real-time PCR (qRT-PCR), and the associated transcription factors
      (TFs) were predicted. RESULTS: Our results revealed that 12 crucial genes might
      affect brain aging, including Trp53, Bcl2, Tnf, Casp9, Fos, Il6, Ptgs2, Il1b,
      Bdnf, Cdkn1a, Pik3c3, Rps6ka1, among which Casp9, Fos, Ptgs2, Cdkn1a, Pik3c3, and
      Rps6ka1 had been verified by qRT-PCR in 10-moth-old SAMP8 mice. Five functional
      groups including mitogen-activated protein kinase (MAPK) signaling pathway,
      neurotrophin signaling pathway, Hepatitis B, Alzheimer's disease and Oxytocin
      signaling pathway were significantly changed during aging process in SAMP8 mice.
      Two key transcription factors of c-Fos and C/EBPbeta were predicted by
      constructing a TF-target gene network. CONCLUSION: These putative genes and
      pathways are closely related to brain senescence and our results would gain new
      insight into the pathogenesis of brain aging.

PMID- 30113007
TI  - Effects of Exercise and Ferulic Acid on Alpha Synuclein and Neuroprotective Heat
      Shock Protein 70 in An Experimental Model of Parkinsonism Disease.
AB  - : In this study we aimed to investigate and to compare the effects of ferulic
      acid (FR), muscle exercise (Ex) and combination of them on rotenone (ROT)-induced
      Parkinson disease (PD) in mice as well as their underlying mechanisms. Thirty
      five male C57BL/6 mice were allocated into 5 equal groups, 1) Normal control
      (CTL) group, 2) ROT group (rats received ROT 3 mg/Kg i.p. for 70 days), 3) FR
      group (rats received ROT + FR at 20 mg/kg/day), 4) Ex group (rats received ROT +
      swimming Ex) and 5) FR+Ex group (rats received ROT + FR and Ex). Compared to CTL
      group, ROT group showed significant impairment in motor performance and
      exploratory behavior with bradykinesia with significant loss of dopaminergic
      neurons (tyrosine hydroxylase, (TH)) and Lowy bodies (alpha synuclein) aggregates
      and significant reduction in Hsp70 expression (p< 0.05). Compared to ROT group,
      other treated groups (FR, EX and FR+Ex) showed significant improvement in motor
      performance, exploratory behavior and bradykinesia, TH density and Hsp70 with
      loss of Lowy bodies aggregates in corpus striatum, however the effect of FR alone
      was more potent than Ex alone (p< 0.05) and addition of Ex to FR caused no more
      significant improvement than FR alone. CONCLUSION: FR and Ex seems to improve the
      motor performance in PD rodent model which might be due to upregulation of Hsp70
      and increasing density of dopaminergic neurons in corpus striatum. FR offers more
      protective effects than Ex and combination of both did not offer more protection
      than FR alone.

PMID- 30113008
TI  - Vigilance States: Central Neural Pathways, Neurotransmitters And Neurohormone.
AB  - : Bakground and objective: The sleep-wake cycle is characterized by a circadian
      rhythm involving neurotransmitters and neurohormones that are released from
      brainstem nuclei and hypothalamus. Aim of this review is to analyze the role
      played by central neural pathways, neurotrasmitters and neurohormones in the
      regulation of vigilance states. METHODS: We analyzed the literature identifying
      relevant articles dealing with central neural pathways, neurotrasmitters and
      neurohormones involved in the control of wakefulness and sleep. RESULTS: The
      reticular activating system is the key center in the control of the states of
      wakefulness and sleep via alertness and hypnogenic centers. Neurotransmitters and
      neurohormones interplay during the dark-light cycle in order to maintain a normal
      plasmatic concentrations of ions, proteins and peripheral hormones, and
      behavioral state control. CONCLUSION: An updated description of pathways,
      neurotransmitters and neurohormones involved in the regulation of vigilance
      states has been depicted.

PMID- 30113009
TI  - Dietary patterns and components to prevent and treat heart failure: a
      comprehensive review of human studies.
AB  - Growing evidence has emerged about the role of dietary patterns and components in
      heart failure (HF) incidence and severity. The objective here is to provide a
      comprehensive summary of the current evidence regarding dietary
      patterns/components and HF. A comprehensive search of online databases was
      conducted using multiple relevant keywords to identify relevant human studies.
      The Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets have
      consistently been associated with decreased HF incidence and severity. Regarding
      specific dietary components, fruit, vegetables, legumes and whole grains appear
      beneficial. Current evidence suggests that red/processed meats, eggs and refined
      carbohydrates are harmful, while fish, dairy products and poultry remain
      controversial. However, there is a notable lack of human intervention trials. The
      existing but limited observational and interventional evidence from human studies
      suggests that a plant-based dietary pattern high in antioxidants, micronutrients,
      nitrate and fibre but low in saturated/trans-fat and Na may decrease HF
      incidence/severity. Potential mechanisms include decreased oxidative stress,
      homocysteine and inflammation but higher antioxidant defence and NO
      bioavailability and gut microbiome modulation. Randomised, controlled trials are
      urgently required.

PMID- 30113010
TI  - Legal reflections on the evolving role of general practitioners in China's
      primary care: an assessment of regulatory strategies.
AB  - : AimTo assess the regulation of the Chinese healthcare system in assisting a
      nationwide implementation of general practitioner (GP) services. BACKGROUND:
      Along with the perennial problems of unaffordable and inequitable healthcare, a
      rapidly ageing population and the increasing burden of non-communicable diseases
      pose challenges to the Chinese healthcare system. Recognising these challenges
      and to satisfy people's demands for more and better healthcare, China has
      initiated a plan, named 'Healthy China 2030', based on the findings from a two
      year joint study by the World Health Organization (WHO) and the World Bank Group
      (WBG) in collaboration with Chinese agencies. The Chinese healthcare plan,
      officially approved in 2016, is an attempt to use the people-centred, integrated
      care (PCIC) model recommended by the WHO and WBG to shape the Chinese healthcare
      system. In accordance with PCIC, China began the implementation of gatekeeping
      primary care by introducing GP services to local communities. METHODS: A
      comparative analysis was employed to point out the importance of introducing GP
      services. A systematic assessment was carried out to evaluate the regulatory
      sector of the Chinese healthcare system, including a critical review of related
      legal norms and a theoretical exploration of external impediments (eg, cultural
      attitudes, government capacity and interest groups).FindingsResults demonstrate
      that the current regulatory sector of the Chinese healthcare system needs to be
      improved in order to assist the nationwide implementation of GP services and to
      strengthen its gatekeeping role. Major deficiencies include the problematic
      relationship between legal norms and health policies, the lack of effective and
      consistent new legislation, the low rate of social acceptance, and lack of
      support from agencies. To address those challenges, this paper recommends that
      preliminary efforts be devoted, in part, to two changes in the legal structure:
      enacting a specific law, and creating an independent regulatory oversight body.

PMID- 30113011
TI  - Development and characterization of monoclonal antibodies against Besnoitia
      besnoiti tachyzoites.
AB  - This is the first report on the development and characterization of eight
      monoclonal antibodies (MABs) generated against whole- and membrane-enriched
      tachyzoite extracts of the apicomplexan parasite Besnoitia besnoiti. Confocal
      laser scanning immunofluorescence microscopy was used to localize respective
      epitopes in B. besnoiti tachyzoites along the lytic cycle. A pattern compatible
      with dense granule staining was observed with MABs 2.A.12, 2.F.3 and 2.G.4, which
      could be confirmed by immunogold electron microscopy for MABs 2.A.12 and 2.F.3.
      In particular, MABs 2.F.3 and 2.G.4 were secreted during early invasion,
      proliferation and egress phases. MABs 3.10.8 and 5.5.11 labelled the tachyzoite
      surface, whilst MABs 1.17.8, 8.9.2 and 2.G.A recognized the apical tip, which is
      reminiscent for microneme localization. Besides, the epitopes recognized by the
      latter two (MABs 8.9.2 and 2.G.A) exhibited a redistribution from the anterior
      part across the parasite surface towards the posterior end during invasion. Most
      MABs developed were genus-specific. Indeed, the MABs cross-reacted neither with
      T. gondii nor with N. caninum tachyzoites. In summary, we have generated MABs
      that will be useful to study the key processes in the lytic cycle of the parasite
      and with additional promising diagnostic value. However, the molecular identity
      of the antigens recognized remains to be elucidated.

PMID- 30113012
TI  - Inadequate benzodiazepine dosing may result in progression to refractory and non
      convulsive status epilepticus.
AB  - Status epilepticus (SE) is defined as ongoing seizures lasting longer than five
      minutes or multiple seizures without recovery. Benzodiazepines (BZDs) are first
      line agents for the management of SE. Our objective was to evaluate BZD dosing in
      SE patients and its effects on clinical/electrographic outcomes. A retrospective
      analysis was conducted from a prospective database of SE patients admitted to a
      university-based neurocritical care unit. The initial presentation and
      progression to refractory SE (RSE) and non-convulsive SE (NCSE) with coma was
      evaluated. Outcome measures included length of stay (LOS), rates of intubation,
      ventilator-dependent days, and Glasgow outcome scale (GOS). The lorazepam
      equivalent (LE) dosage of BZDs administered was calculated and we analysed
      variations in progression if 4 mg or more of LE (adequate BZDs) was administered.
      Among 100 patients, the median dose of LE was 3 mg (IQR: 2-5 mg). Only 31% of
      patients received adequate BZDs. Only 18.9% of patients with NCSE without coma
      received adequate BZDs (p=0.04). Among patients progressing to RSE, 75.4% had not
      received adequate BZDs (p=0.04) and among patients developing NCSE with coma,
      80.6% did not receive adequate BZDs (p=0.07). Escalating doses of BZDs were
      associated with a decrease in cumulative incidences of RSE (correlation
      coefficient r=-0.6; p=0.04) and NCSE with coma (correlation coefficient r=-0.7;
      p=0.003). Outcome measures were not influenced by BZD dosing. The majority of our
      patients were not adequately dosed with BZDs. Inadequate BZD dosing progressed to
      RSE and had a tendency to lead to NCSE with coma. Our study demonstrates the need
      to develop a hospital-wide protocol to guide first responders in the management
      of SE.

PMID- 30113013
TI  - Crystal growth and magnetic characterization of HoIr2Si2 (I4/mmm).
AB  - Single crystals of HoIr2Si2 with the body-centered ThCr2Si2-type structure
      (I4/mmm) were grown by Bridgman method from indium flux. Single crystal structure
      determination yielded a Si-z position of 0.378(1) in the structure. We excluded
      the presence of the high temperature phase with the primitive CaBe2Ge2-type
      structure (P4/nmm) by powder x-ray diffraction. Magnetic measurements on the
      single crystals yield a Neel temperature of [Formula: see text] K. In the inverse
      magnetic susceptibility a strong anisotropy with Weiss temperatures [Formula: see
      text] K and [Formula: see text] K occurs above T N. The effective magnetic moment
      [Formula: see text] and [Formula: see text] is close to the expected value for a
      free Ho3+ ion, [Formula: see text]. The field dependent magnetization shows a
      step-like behaviour due to crystalline electric field effects. The temperature
      and field dependence of the magnetization hint to the ordering of the magnetic
      moments along the c direction below T N.

PMID- 30113014
TI  - Confinement effects, surface effects, and transport in Bi and Bi1-x Sb x
      semiconducting and semimetallic nanowires.
AB  - Hicks and Dresselhaus predicted that quantum well and nanowire thermoelectric
      materials could show a meaningful enhancement of the heat-to-electricity
      conversion efficiency compared to their bulk counterparts. The unique transport
      properties of bismuth, specifically the low effective mass, high mobility, and
      large Bohr radius of its charge carriers, enabled the study of size-quantization
      effects in Bi nanowires following those theoretical predictions. In this review,
      the band structure of Bi and Bi1-x Sb x alloys is discussed as a function of
      their composition, temperature, and size-quantization effects. Further, the
      theoretical basis of the thermoelectric performance enhancement in Bi nanowires
      is reviewed and compared to experimental data. Single-wire conductivity and Hall
      data are reviewed. Finally, several synthesis routes for Bi1-x Sb x nanowire
      samples are discussed, including liquid pressure impregnation, vapor
      impregnation, electrochemical deposition and wet chemistry impregnation in a
      template.

PMID- 30113015
TI  - Deep learning with cinematic rendering: fine-tuning deep neural networks using
      photorealistic medical images.
AB  - Deep learning has emerged as a powerful artificial intelligence tool to interpret
      medical images for a growing variety of applications. However, the paucity of
      medical imaging data with high-quality annotations that is necessary for training
      such methods ultimately limits their performance. Medical data is challenging to
      acquire due to privacy issues, shortage of experts available for annotation,
      limited representation of rare conditions and cost. This problem has previously
      been addressed by using synthetically generated data. However, networks trained
      on synthetic data often fail to generalize to real data. Cinematic rendering
      simulates the propagation and interaction of light passing through tissue models
      reconstructed from CT data, enabling the generation of photorealistic images. In
      this paper, we present one of the first applications of cinematic rendering in
      deep learning, in which we propose to fine-tune synthetic data-driven networks
      using cinematically rendered CT data for the task of monocular depth estimation
      in endoscopy. Our experiments demonstrate that: (a) convolutional neural networks
      (CNNs) trained on synthetic data and fine-tuned on photorealistic cinematically
      rendered data adapt better to real medical images and demonstrate more robust
      performance when compared to networks with no fine-tuning, (b) these fine-tuned
      networks require less training data to converge to an optimal solution, and (c)
      fine-tuning with data from a variety of photorealistic rendering conditions of
      the same scene prevents the network from learning patient-specific information
      and aids in generalizability of the model. Our empirical evaluation demonstrates
      that networks fine-tuned with cinematically rendered data predict depth with
      56.87% less error for rendered endoscopy images and 27.49% less error for real
      porcine colon endoscopy images.

PMID- 30113016
TI  - Antiferromagnetic successive superexchange interactions underlying ferromagnetic
      couplings in codoped diluted magnetic semiconductors.
AB  - Our recent works have revealed that the magnetic coupling among the magnetic
      codopants in diluted magnetic semiconductors and doped transition metal oxides
      has a strong local feature. This was attributed to successive spin polarizations
      induced by the codopants to their neighboring anion ligands. In the present work,
      we analyze and refine the successive spin polarization based magnetic coupling
      using results of ab initio calculations and assign the magnetic coupling among
      the magnetic codopants to a combination of superexchange and double-exchange
      interactions. In particular, it is shown that antiferromagnetic successive
      superexchange interactions can lead to a ferromagnetic coupling between two
      magnetic dopants mediated by a suitable codopant with the latter forming a
      ferromagnetic double exchange coupling with its first nearest neighbor anions
      which couple it with the magnetic cations. This is exemplified by ab initio
      results for the magnetic coupling of two Co-dopants in the presence of a mediated
      Cu codopant in the environment of various hosts, namely ZnO, GaN, GaP, TiO2, CdS
      and SnO2. Additional results for other codopant pairs in various hosts are also
      presented.

PMID- 30113017
TI  - Dynamics of a single hole in the Heisenberg-Kitaev model: a self-consistent Born
      approximation study.
AB  - The magnetic properties of 4d and 5d transition-metal insulating compounds with
      the honeycomb structure are believed to be described by the Heisenberg-Kitaev
      model, which contains both the isotropic Heisenberg interaction J and anisotropic
      Kitaev interaction K. In this paper, we study the single-hole propagation of the
      t-J-K model in various magnetically ordered phases by the self-consistent Born
      approximation. We find that there are low-energy coherent quasiparticle (QP)
      excitations in all of these phases which appear firstly around the K point in the
      first Brillouin zone (BZ), but the bandwidths of these QPs are very small due to
      the hole-magnon coupling. Interestingly, in the zigzag phase relevant to recent
      experiments, though the QP weights are largely suppressed in the physical spectra
      in the first BZ, we find that they recover in the extended BZs. Moreover, our
      results reveal that the low-energy QP spectra are reduced with the increase of K.

PMID- 30113018
TI  - Linear energy transfer (LET) spectra and survival fraction distribution based on
      the CR-39 plastic charged-particle detector in a spread-out Bragg peak
      irradiation by a 12C beam.
AB  - Facilities for heavy ion therapies are steadily increasing in number worldwide.
      One of the advantages of heavy ions is their high relative biological effect
      (RBE). In a model used at NIRS (National Institute of Radiological Sciences),
      linear energy transfer (LET) spectra are required to estimate biological dose
      (physical dose  *  RBE). The CR-39 plastic charged-particle detector (CR-39) is
      suitable for measurement of LET. For the present study, done at the Gunma
      University Heavy Ion Medical Center (GHMC), we measured LET spectra at 11 depths
      in spread-out Bragg peak (SOBP) irradiation by a 12C beam of 380 MeV/u. The lower
      threshold of the CR-39 to measure LET was about 5 keV um-1 due to poor
      sensitivity for low LET. Then we calculated biological dose and survival fraction
      distributions and compared them with treatment planning results at GHMC. We used
      Monte Carlo simulation (Geant4) to calculate LET spectra. The simulation results
      were in good agreement with the experimental spectra. Moreover, the biological
      dose and survival fraction distributions estimated from the CR-39 reproduced the
      treatment planning. The CR-39 is suitable for estimating biological dose in
      carbon ion therapy.

PMID- 30113019
TI  - Unfavorably altered plasma clot properties in women with a HERDOO2 score equal to
      or greater than 2 and prediction of recurrent venous thromboembolism.
AB  - Introduction The HERDOO2 rule can help identify patients in whom anticoagulation
      can be safely discontinued. Unfavorably altered fibrin clot properties predict
      recurrent venous thromboembolism (VTE). Objectives We aimed to assess a possible
      association between fibrin clot properties and the HERDOO2 score in women after
      unprovoked VTE. Patients and methods Eighty women younger than 70 years after a
      first unprovoked VTE separately and combined with 32 women after hormone-related
      VTE were followed for a median of 48.5 months (interquartile range, 37.5-67
      years). Plasma fibrin clot permeability (Ks), lysability, turbidity measurements,
      and thrombin generation were assessed 3 months after the index event in relation
      to the HERDOO2 score. Results Nineteen women (23.8%) with a HERDOO2 score equal
      to or higher than 2 were characterized by lower Ks (-6.8%), indicating formation
      of more compact clots, impaired fibrinolysis as evidenced by a reduced maximum
      rate of D-dimer release from clots (D-D rate, by 6.8%), and prolonged clot lysis
      time (CLT, by 23.8%). No increased thrombin generation or differences in the
      remaining fibrin clot properties were observed. When combined with estrogen
      related VTE, the same trends were observed. D-D rate and CLT correlated with the
      HERDOO2 score (r = -0.28, P = 0.01 and r = 0.35, P = 0.002, respectively) in 80
      women with unprovoked VTE. Unfavorable clot phenotype, defined as Ks <=6.55*10-9
      cm2 and CLT >99.5 minutes, was associated with high risk of recurrence in the
      HERDOO2 rule (P = 0.02). Conclusions We showed that middle-aged women after
      unprovoked VTE with high risk of recurrence based on the HERDOO2 rule are
      characterized by formation of denser fibrin clots and impaired fibrinolysis.

PMID- 30113020
TI  - The first Polish cohort of adult patients with common variable immunodeficiency
      from 4 specialized centers: do we provide standards of care?

PMID- 30113021
TI  - Increased Concentrations of Extracellular Histones in Patients with Tuberculous
      Pleural Effusion.
AB  - BACKGROUND Extracellular histones have recently been suggested as critical
      mediators in many inflammatory diseases. However, the role of extracellular
      histones in tuberculous pleural effusion (TPE) is unclear. The goal of this study
      was to explore the potential involvement of extracellular histones in patients
      with TPE. MATERIAL AND METHODS Samples of pleural effusion and peripheral blood
      were obtained from 58 patients with tuberculosis. Extracellular histones were
      determined in both TPE and serum samples. Moreover, the biomarkers for cellular
      damage, inflammatory cell activation, and systemic inflammation including lactate
      dehydrogenase (LDH), myeloperoxidase (MPO), S100A8/A9, as well as multiple
      inflammatory cytokines were measured. RESULTS Extracellular histone levels were
      significantly elevated in TPE (4.762 mg/mL [3.336, 7.307]) and serum samples
      (1.502 mg/mL [1.084, 2.478]) from tuberculosis patients as compared with the
      serum (0.585 mg/mL [0.285, 0.949]) from healthy controls. Notably, extracellular
      histones in TPE were also much higher than in serum of patients (P=0.002). LDH,
      MPO, and S100A8/A9 levels were all increased in TPE, along with a remarkable
      elevation of various cytokines. A correlation analysis showed that extracellular
      histones were positively associated with LDH, MPO, and S100A8/A9, and a panel of
      inflammatory cytokines in TPE. CONCLUSIONS These results suggest that high
      concentrations of extracellular histones are markedly present in TPE, which may
      play an inflammatory role towards the progression of tuberculosis.

PMID- 30113022
TI  - [The Rice OsDUF810 Family: OsDUF810.7 May be Involved in the Tolerance to Salt
      and Drought].
AB  - With the advance of sequencing technology, the number of sequenced plant genomes
      has been rapidly increasing. However, understanding of the gene function in these
      sequenced genomes lags far behind; as a result, many coding plant sequences in
      public databases are annotated as proteins with domains of unknown function
      (DUF). Function of a protein family DUF810 in rice is not known. In this study,
      we analysed seven members of OsDU810 (OsDUF810.1-OsDUF810.7) family with three
      distinct motifs in rice Nipponbare. By phylogenetic analysis, OsDUF810 proteins
      fall into three major groups (I, II, III). Expression patterns of the seven
      corresponding OsDUF810 protein-encoding genes in 15 different rice tissues vary.
      Under drought, salt, cold and heat stress conditions and ABA treatment, the
      expression of OsDUF810.7 significantly increases. Overexpression of this protein
      in E. coli lead to a significant enhancement of catalase (CAT) and peroxidase
      (POD) activities, and improved bacterial resistance to salt and drought.

PMID- 30113023
TI  - [Algorithm for Physiological Interpretation of Transcriptome Profiling Data for
      Non-Model Organisms].
AB  - Modern techniques of next-generation sequencing (NGS) allow obtaining expression
      profile of all genes and provide an essential basis for characterizing metabolism
      in the organism of interest on a broad scale. An important condition for
      obtaining a demonstrative physiological picture using high throughput sequencing
      data is the availability of the genome sequence and its sufficient annotation for
      the target organism. However, a list of species with properly annotated genomes
      is limited. Transcriptome profiling is often performed in the so-called non-model
      organisms, which are those with unknown or poorly assembled and/or annotated
      genome sequences. The transcriptomes of non-model organisms are possible to
      investigate using algorithms of de novo assembly of the transcripts from
      sequences obtained as the result of RNA sequencing. A physiological
      interpretation of the data is difficult in this case because of the absence of
      annotation of the assembled transcripts and their classification by metabolic
      pathway and functional category. An algorithm for transcriptome profiling in non
      model organisms was developed, and a transcriptome analysis was performed for the
      basidiomycete Lentinus edodes. The algorithm includes open access software and
      custom scripts and encompasses a complete analysis pipeline from the selection of
      cDNA reads to the functional classification of differentially expressed genes and
      the visualization of the results. Based on this algorithm, a comparative
      transcriptome analysis of the nonpigmented mycelium and brown mycelial mat was
      performed in L. edodes. The comparison revealed physiological differences between
      the two morphogenetic stages, including an induction of cell wall biogenesis,
      intercellular communication, ion transport, and melanization in the brown
      mycelial mat.

PMID- 30113024
TI  - [Mutation Frequencies in RNAi Targets in HIV-1 Genomes Obtained from Blood Plasma
      of Patients Receiving Anti-Retroviral Therapy].
AB  - Gene therapy for AIDS based on RNA interference (RNAi) is currently looked upon
      as a promising alternative to conventional antiretroviral chemotherapy. The high
      variability of HIV-1 is the main challenge in developing new approaches to AIDS
      therapy. To date, about 18 million HIV-1 infected individuals receive
      antiretroviral therapy worldwide. As of 2017, about 44% of individuals with AIDS
      received antiretroviral therapy in Russia. Since the RNAs used for efficient RNAi
      and the corresponding targets in the viral transcript should be perfectly
      complementary to each other, it is necessary to continuously monitor the
      nucleotide sequences of clinical HIV-1 isolates obtained from blood and cells of
      naive patients and patients receiving antiretroviral therapy. Comprehensive
      analysis of the mutation frequencies in the viral genome is only possible with
      deep sequencing approaches. The present paper reports on an analysis of the
      mutation frequencies in six 100 bp genome regions in clinical HIV-1 isolates
      obtained from blood plasma of four Russian AIDS patients who have been receiving
      antiretroviral therapy for several years. These regions contain efficient RNAi
      targets. The average frequencies of all possible transversions and transitions
      within the RNAi targets and in their proximity have been estimated. It has been
      demonstrated that reverse transcriptase inhibition decreases the frequency of a
      number of reverse mutations. It has been found that mutations in RNAi targets are
      rarer (5-75 times lower than the mutation frequency for different nucleotide
      substitutions) than in the adjacent sequences. Our findings speak in favor of
      these conservative targets for developing new approaches to gene therapy of AIDS.

PMID- 30113025
TI  - [CAX3 Gene is Involved in Flax Response to High Soil Acidity and Aluminum
      Exposure].
AB  - Understanding the molecular mechanisms of plant response to unfavorable
      conditions is necessary for the effective selection of tolerant genotypes.
      Earlier, using high-throughput transcriptome sequencing of flax plants after
      exposure to aluminum ions (Al^(3+)) and high soil acidity, we detected stress
      induced alteration in the expression of several genes, including CAX3, which
      encodes Ca^(2+)/H^(+)-exchanger involved in calcium ion transport. Here we
      describe CAX3 mRNA levels in flax cultivars either tolerant (Hermes and TMP1919)
      or sensitive (Lira and Orshanskiy) to Al^(3+). Stress-induced increased
      expression of CAX3 was detected only in aluminum-tolerant flax cultivars. The
      product of CAX3 gene may participate in flax response to high soil acidity and
      high Al^(3+) concentration through Ca^(2+)-mediated intracellular regulation.

PMID- 30113026
TI  - [In silico Analyses of Transcriptomes of the Marine Green Microalga Dunaliella
      tertiolecta: Identification of Sequences Encoding P-type ATPases].
AB  - De novo assembled transcriptomes of the marine microalga Dunaliella tertiolecta
      (Chlorophyta) were analyzed. Transcriptome assemblies were performed using short
      read RNA-seq data deposited in the SRA database (DNA and RNA Sequence Read
      Archive, NCBI). A merged transcriptome was assembled using a pooled RNA-seq data
      set. The goal of the study was in silico identification of nucleotide sequences
      encoding P-type ATPases in D. tertiolecta transcriptomes. P-type ATPases play a
      considerable role in the adaptation of an organism to a variable environment, and
      this problem is particularly significant for microalgae inhabiting an environment
      with an unstable ionic composition. Particular emphasis was given to searching
      for a sequence coding Na^(+)-ATPase. This enzyme is expected to function in the
      plasma membrane of D. tertiolecta like in some marine algae, in particular, in
      the closely related alga Dunaliella maritima. An ensemble of 12 P-type ATPases
      consisting of members belonging to the five main subfamilies of the P-type ATPase
      family was revealed in the assembled transcriptomes. The genes of the following P
      type ATPases were found: (1) heavy metal ATPases (subfamily PIB); (2) Ca^(2+)
      ATPases of SERCA type (subfamily P2A); (3) H^(+)-ATPases (subfamily P3); (4)
      phospholipid-transporting ATPases (flippases) (subfamily P4); (5) cation
      transporting ATPases of uncertain specificities (subfamily P5). The presence of
      functional Na^(+)-ATPases in marine algae is presently undoubted. However,
      contrary to expectations, we failed to find a nucleotide sequence encoding a
      protein that could unequivocally be considered a Na^(+)-ATPase. Further study is
      necessary to elucidate the roles of in silico revealed D. tertiolecta ATPases in
      Na^(+) transport.

PMID- 30113027
TI  - [Cytotoxicity of Malondialdehyde and Cytoprotective Effects of Taurine via
      Oxidative Stress and PGC-1alpha Signal Pathway in C2C12 Cells].
AB  - One of the end-products of ROS-induced peroxidation, malondialdehyde (MDA),
      induces the cross-links in proteins, which leads to perturbation of the
      physiological functions of cells and contributes to abnormal biological
      regulation and various disorders. Taurine (2-aminoethanesulfonic acid, Tau) aids
      in adjusting normal physiological functions to confer stress resistance. The
      protective effects of Tau against MDA stress in vitro or in vivo were reported
      previously. In this study, we had investigated the protective effects of taurine
      on viability, oxidative stress levels and mitochondrial biogenesis in mouse
      muscle C2C12 cells undergoing MDA induced stress. We show that the treatment with
      100 MUM MDA leads to increase in cell oxidative stress levels, inhibition of
      mitochondrial biogenesis and the reduction of the cell survival rates. The
      pretreatment with 0.1 MUM taurine reduced MDA-induced death rate via inhibition
      of oxidative stress, restoration of mitochondrial functions of the mitochondrial
      membrane potential (MMP) and ATP production. In MDA stress, the pre-treatment
      with 0.1 MUM taurine leads to upregulation of the factors of mitochondrial
      biogenesis. These observations suggest that the cytoprotective effects of taurine
      may be due to an induction of mitochondrial biogenesis.

PMID- 30113028
TI  - [Development and Optimization of Therapeutic Analogues of Anti-TNFalpha Antibody
      Infliximab].
AB  - Previously, we have reported the crystal structures of Fab fragment of Infliximab
      in complex with TNFalpha. The structurally identified epitope on TNFalpha
      revealed the mechanism of TNFalpha inhibition by partially overlapping with the
      TNFalpha-receptor interface and the possibility to optimize the binding affinity.
      In this study, we launched a screen of a phage display library to isolate novel
      anti-TNFalpha antibodies based on the infliximab epitope. To develop novel anti
      TNFalpha antibodies, structural analysis, the phage display antibody isolation,
      step by step antibody optimization, CDR residues random mutagenesis, and binding
      affinity characterization were performed. One of the novel antibodies generated
      on the backbone of infliximab, Inf3D6, has the superior binding affinity to
      TNFalpha, thus, demonstrating the potential for structure guided optimization for
      improvement of existing antibody-based therapeutics.

PMID- 30113029
TI  - [Modification of Anti-Glycan IgG and IgM Profiles in Allergic Inflammation].
AB  - Glycans and anti-glycan antibodies (AGAs) are essential for infiltration of
      inflammatory cells in various allergies. The glycocalyx structure of the cells is
      modified during disease progression, and this modification is possible to
      evaluate by assessment of AGAs. A printed glycan array with 55 immobilized
      glycans and immobilized antibodies to IgG, IgA, and IgM was used to study the
      changes in AGA profiles in bronchial asthma (BA). Levels of antibodies to certain
      glycans in BA patients statistically differed from levels in healthy donors (p <
      0.0007 by the Mann-Whitney test); the glycan set included 6Su-6'-SiaLec, Sia LeX,
      Sia6Htype2; Talphaalpha, Manbeta1-4GlcNAc, and Manalpha1-4Manbeta. The obtained
      results help to better understand the mechanisms of the cell-mediated immune
      response in bronchial asthma and other types of allergic reactions.

PMID- 30113030
TI  - [Mutations in Hemagglutinin and Polymerase Alter the Virulence of Pandemic
      A(H1N1) Influenza Virus].
AB  - To study the pathogenicity factors of the pandemic A(H1N1) influenza virus, a
      number of mutant variants of the A/Hamburg/5/2009 (H1N1)pdm09 strain were
      obtained through passage in chicken embryos, mouse lungs, and MDCK cell culture.
      After 17 lung-to-lung passages of the A/Hamburg/5/2009 in mice, the minimum
      lethal dose of the derived variant decreased by five orders of magnitude compared
      to that of the parental virus. This variant differed from the original virus by
      nine amino acid residues in the following viral proteins: hemagglutinin (HA),
      neuraminidase (NA), and components of the polymerase complex. Additional
      passaging of the intermediate variants and cloning made it possible to obtain
      pairs of strains that differed by a single amino acid substitution. Comparative
      analysis of replicative activity, receptor specificity, and virulence of these
      variants revealed two mechanisms responsible for increased pathogenicity of the
      virus for mice. Thus, (1) substitutions in HA (Asp225Gly or Gln226Arg) and
      compensatory mutation decreasing the charge of HA (Lys123Asn, Lys157Asn,
      Gly158Glu, Asn159Asp, or Lys212Met) altered viral receptor-binding specificity
      and restored the functional balance between HA and NA; (2) Phe35Leu substitution
      in the PA protein increased viral polymerase activity.

PMID- 30113031
TI  - [Oncolytic Properties of a Mumps Virus Vaccine Strain in Human Melanoma Cell
      Lines].
AB  - The oncolytic potential of the attenuated mumps virus (MV) vaccine strain
      Leningrad-3 (L-3) was evaluated in a panel of four human metastatic melanoma cell
      lines. The lines were shown to be susceptible and permissive to MV infection.
      Efficient MV replication led to death of melanoma cells, but the effect differed
      among the cell lines. Possible mechanisms mediating the selectivity of MV L-3
      towards the cell lines were explored. Replicative and oncolytic activity of MV
      was found to depend on the expression pattern of type I interferon genes. None of
      the melanoma cell lines showed induction of expression of the total spectrum of
      genes required to inhibit virus replication. Based on the results, MV L-3 was
      assumed to be a promising oncolytic agent for human melanoma cells.

PMID- 30113032
TI  - [Expression of SLC30A10 and SLC23A3 Transporter mRNAs in Caco-2 Cells Correlates
      with an Increase in the Area of the Apical Membrane].
AB  - Drug bioavailability studies commonly employ in vitro barrier tissue models
      consisting of epithelial and endothelial cells. These experiments require that
      the cell barrier quality be assessed regularly, which is usually performed using
      various labeled substrates and/or evaluation of transepithelial
      (transendothelial) electrical resistance (TEER). This technique provides
      information on the integrity of the monolayer, but not on differentiation-induced
      changes in the cell morphology. The present work shows that impedance
      spectroscopy can be applied to monitor both the integrity of the monolayer and
      the morphological changes of Caco-2 cells. The growth kinetics of the apical
      membrane was determined by calculating the electrical capacitance of the cell
      monolayer. In the course of differentiation, the most pronounced changes in the
      expression levels were observed for the mRNAs that encode SLC30A10 and SLC23A3
      transporters. Their increase correlated with an increase in the apical membrane
      area, indicating that SLC30A10 and SLC23A3 mRNA levels assessed by qRT-PCR may be
      employed as cell differentiation biomarkers in Caco-2 models.

PMID- 30113033
TI  - [Ribosome Inactivation and the Integrity of the Intestinal Epithelial Barrier].
AB  - The mistletoe lectin viscumin (MLI) is a ribosome-inactivating protein from
      Viscum album widely used in cancer therapy. Its antitumor properties are due to
      its immunomodulating action, previously demonstrated in experiments involving
      intravenous, subcutaneous, and oral administration of viscumin. To investigate
      whether viscumin has a cytotoxic effect on the intestinal epithelium, its safety
      was assessed using (i) impedance spectroscopy to measure the integrity of the
      colorectal adenocarcinoma Caco-2 cell monolayer after exposure to viscumin and
      (ii) a novel technique of determining the portion of viscumin-inactivated
      ribosomes. It was shown that inactivation of at least 20% of the ribosomes within
      6 h did not lead to disruption of the Caco-2 cell monolayer or alter the
      physicochemical parameters of enterocyte membranes.

PMID- 30113034
TI  - [Enalaprilat Inhibits Zinc-Dependent Oligomerization of Metal-Binding Domain of
      Amyloid-beta Isoforms and Protects Human Neuroblastoma Cells from Toxic Action of
      these Isoforms].
AB  - Intact amyloid-beta peptides (Abeta) may undergo prion-like aggregation when they
      interact with chemically or structurally modified variants of Abeta present in
      extracellular pathohistological inclusions (amyloid plaques). This aggregation is
      regarded as one of the key molecular mechanisms of Alzheimer's disease (AD)
      pathogenesis. Zinc ions are involved in the pathological dimerization and
      oligomerization of natural Abeta isoforms, and zinc-induced oligomers can also
      initiate the pathological aggregation of Abeta. Based on the earlier found
      molecular mechanism of zinc-dependent oligomerization of Abeta, it has been
      suggested that the targeted inhibition of the 11EVHH14 site in one Abeta molecule
      from zinc-mediated interactions with the same site of another Abeta molecule can
      effectively inhibit the oligomerization and aggregation of Abeta. Taking into
      account the similarity in the structural organization of zinc-binding sites
      within Abeta and angiotensin-converting enzyme (ACE), we hypothesized that
      inhibitors of the ACE active sites could specifically interact with the 11EVHH14
      site of Abeta. Using a surface plasmon resonance biosensor and nuclear magnetic
      resonance spectroscopy, we have found that the ACE inhibitor enalaprilat
      effectively inhibits zinc-dependent dimerization of the metal-binding domains of
      intact Abeta and Abeta with isomerized Asp7 (isoAbeta). We have also found that
      enalaprilat protects SH-SY5Y human neuroblastoma cells from the toxic effects of
      Abeta(1-42) and isoAbeta(1-42), which are among the most common components of
      amyloid plaques. The results confirm the role of zincdependent oligomerization of
      Abeta in AD pathogenesis and make it possible one to consider enalaprilat as a
      prototype of antiaggregation agents for treating AD.

PMID- 30113035
TI  - [Mutations in the Effector Domain of RhoV GTPase Impair Its Binding to Pak1
      Protein Kinase].
AB  - Atypical RhoV GTPase (Chp/Wrch-2) is a member of the human Rho GTPase family,
      which belongs to the superfamily of Ras-related small GTPases. The biological
      functions of RhoV, regulation of its activity, and mechanisms of its action
      remain largely unexplored. Rho GTPases regulate a wide range of cellular
      processes by interacting with protein targets called effectors. Several putative
      RhoV effectors have been identified, including protein kinases of the Pak (p21
      activated kinase) family: Pak1, Pak2, Pak4, and Pak6. RhoV GTPase activates Pak1
      protein kinase and simultaneously induces its ubiquitin-dependent degradation.
      Pak1 regulates E-cadherin localization at adherens junctions downstream of RhoV
      during gastrulation in fish. The effector domain of RhoV mediates its binding to
      the CRIB (Cdc42/Rac1 interactive binding) motif in the N-terminal p21-binding
      domain (PBD) of Pak6 protein kinase. The role of the RhoV effector domain in
      mediating interaction with Pak1 has not been studied. This study has identified
      mutations in the effector domain of RhoV GTPase (Y60K, T63A, L65A, and D66A) that
      impair its interaction with Pak1 in the GST-PAK-PBD pull-down assay and
      coimmunoprecipitation. Our results suggest that the effector domain of RhoV
      mediates its binding to Pak1, complementing the current view of the molecular
      basics of RhoV binding to effectors of the Pak family. These data lay the basis
      for further studies on the role of Pak1 in RhoV-activated signaling pathways and
      cellular processes.

PMID- 30113036
TI  - [In silico Search for Tubulin Polymerization Inhibitors].
AB  - Cytostatic colchicine is widely used in the treatment of Familial Mediterranean
      fever, but it has several side effects. For finding new, more effective drugs
      with higher affinity and diminishside effects we carried out virtual screening of
      potential inhibitors of the main target of colchicine, the polymerization of
      tubulin by evaluating affinity 25745 compounds, structurally related to the
      colchicine. We have identified 11 commercially available compounds with higher
      affinity to tubulin. Compounds with highest binding scores include
      trimethoxybenzene and its derivatives; these compounds bind to the same site in
      similar orientation. Information provided can form the basis for design of new
      cytostatics.

PMID- 30113037
TI  - [Ultrasonic Footprinting].
AB  - Ligand binding influences the dynamics of the DNA helix in both the binding site
      and adjacent regions. This, in particular, is reflected in the changing pattern
      of cleavage of complexes under the action of ultrasound. The specificity of
      ultrasound-induced cleavage of the DNA sugar-phosphate backbone was studied in
      actinomycin D (AMD) complexes with double-stranded DNA restriction fragments.
      After antibiotic binding, the cleavage intensity of phosphodiester bonds between
      bases was shown to decrease at the chromophore intercalation site and to increase
      in adjacent positions. The character of cleavage depended on the sequences
      flanking the binding site and the presence of other AMD molecules bound in the
      close vicinity. A comparison of ultrasonic and DNase I cleavage patterns of AMD
      DNA complexes provided more detail on the local conformation and dynamics of the
      DNA double helix in both binding site and adjacent regions. The results pave the
      way for developing a novel approach to studies of the nucleotide sequence
      dependence of DNA conformational dynamics and new techniques to identify
      functional genome regions.

PMID- 30113038
TI  - [CTAB-PEG DNA Extraction from Fungi with High Contents of Polysaccharides].
AB  - Polysaccharides influence concentration and purity of extracted DNA. Here we
      present rapid and efficient protocol for DNA extraction from samples rich in
      polysaccharides. The technique has been developed using cultures of Schizophyllum
      commune and involves a modification of known Cetyltrimethyl Ammonium Bromide
      (CTAB) protocol. To remove polysaccharides, Polyethylene Glycol (PEG) 8000 was
      added during DNA precipitation. Genomic DNA obtained with the CTAB-PEG method had
      high integrity, with average fragment size >30 kb, the concentration higher than
      100 ng/MUL, and the yield more than 30 MUg/g. Presented technique is suitable for
      DNA extraction from fungi, bacteria, archaea or even mollusks with high
      polysaccharide content.

PMID- 30113039
TI  - [Immuno-PCR Assay for Quantitation of Antibodies to Epstein-Barr Virus].
AB  - Successful disease prevention and therapy critically depend on timely diagnosis
      of infections. Quantitative immuno-PCR (qiPCR) technology improves the
      sensitivity in the detection of antibodies to pathogens. A qiPCR-based assay was
      developed to determine IgG antibodies to Epstein-Barr virus (EBV) in the human
      blood serum. EBV nuclear protein 1 fragment (pEBV) was expressed in Escherichia
      coli. A synthetic single-stranded deoxyribonucleotide was conjugated to
      streptavidin, and the conjugate was used to detect rEBV-IgG1-biotin complexes by
      qiPCR. The IgG1 titers determined by qiPCR were compared to the results of enzyme
      linked immunosorbent assay (ELISA). The sensitivity of qiPCR was one order of
      magnitude higher than that of ELISA. Thus, a highly sensitive qiPCR-based assay
      was developed to quantitate antibodies specific to the recombinant EBV antigen.

PMID- 30113040
TI  - Precise surface structure of nanofibres with nearly atomic-level precision.
AB  - We report the first example of endowing the surface structure of a polymeric
      assembly with nearly atomic-level precision. The solenoidal wrapping of a DNA
      chain around the surface of a nanofibre transcribes the precise sequence
      structure of the DNA onto the nanofibre surface, resulting in a precise surface
      structure.

PMID- 30113041
TI  - Innovative HPTLC method with fluorescence detection for assessment of febuxostat
      montelukast combination and study of their protective effects against gouty
      arthritis.
AB  - The present study was designed to evaluate the potential protective effects of
      the cysteinyl leukotriene receptor blocker montelukast (MNK) and the xanthine
      oxidase inhibitor febuxostat (FBX) and their combination on a model of acute
      gouty arthritis induced by intraarticular injection of monourate sodium crystal
      (MUC) injection in rats. Additionally, we established an HPTLC method for the
      quantitative determination of both drugs simultaneously and applied this method
      to detect this combination in rat plasma. In this study, the treated male Wistar
      rats were grouped as follows: a negative control group injected with phosphate
      buffer saline (PBS) and a positive control group injected with MUC in their
      tibiotarsal joint. Four groups were treated orally with diclofenac (4 mg kg-1),
      MNK (10 mg kg-1), FBX (5 mg kg-1) and MNK plus FBX before MUC injection in their
      tibiotarsal joints. MUC injection in joints without pretreatment led to a
      progressive significant increase in joint diameter and heavy leucocytic
      infiltration compared to the PBS-injected joints. Treatment with diclofenac or a
      combination of MNK and FBX significantly decreased both joint diameters and
      leucocytic infiltration compared to the MUC group. MNK or FBX treatment
      attenuated leucocytic infiltration and significantly decreased joint diameters
      compared to the MUC group. Thus, MNK and FBX can prevent the development of MUC
      induced acute gouty arthritis in rats. Also, MNK can be an alternative preventive
      treatment, particularly in elderly patients who cannot tolerate NSAIDs or
      corticosteroid. Furthermore, a new thin-layer chromatographic method combined
      with fluorescence detection was developed and validated for the simultaneous
      estimation of a mixture of FBX and MNK in spiked human plasma. In this method, we
      employed TLC aluminium plates precoated with silica gel G 60F254 as the
      stationary phase and chloroform : methanol (9 : 1, v/v) as the mobile phase. The
      optimized mobile phase selected for development gives compact bands (Rf values
      are 0.28 and 0.63 for FBX and MNK, respectively). The emission intensities were
      measured using a K400 optical filter after excitation at 322 nm. The linear
      regression data for the calibration plots showed excellent linear relationship (r
      = 0.9990 and 0.9996 for FBX and MNK, respectively), and the linearity range was
      10.0-800.0 ng per band for both drugs. According to ICH-guidelines, this method
      was validated for precision, accuracy, robustness and selectivity. Also, the
      limits of detection and quantitation were calculated. In addition, stability
      studies on the studied mixture were performed. Statistical analysis proved that
      this method is reproducible and selective for the estimation of a mixture of FBX
      and MNK.

PMID- 30113042
TI  - Melanoma - role of the environment and genetics.
AB  - Melanoma rates have increased in populations that are mainly European. The main
      etiologic factor is ultraviolet radiation, from the sun as well as artificial
      tanning devices. Host factors such as skin color, number of nevi, hair and eye
      color and tanning ability are critical factors in modifying an individual's
      response to the sun. Genetic factors interact with host factors and environmental
      factors to increase risk. This review summarizes our current knowledge of
      environment and genetics on melanoma risk and on gene-environment interaction.

PMID- 30113043
TI  - Ultrasound-assisted liquid-liquid spray extraction for the determination of multi
      class trace organic compounds in high-volume water samples.
AB  - In order to extract trace organic compounds (TrOCs) from large volumes of water
      (over 10 L), an ultrasound-assisted liquid-liquid spray extraction (UA-LLSE)
      technique is proposed. The UA-LLSE integrates liquid-liquid extraction, spray
      atomisation and ultrasonication in a single step. Under an acoustic field, a
      water sample is continuously spray injected into an extracting organic solvent to
      generate numerous water microdroplets in the organic phase. As a result, the
      extraction time and efficiency are significantly improved through increasing the
      interactive surface area, collision probability and mass transfer between two
      liquid phases. Other major parameters affecting the extraction efficiency such as
      nozzle type, spray angle, flow rate, nozzle position, ultrasonication energy, and
      extraction cycle were optimised. This newly developed technique has been applied
      to determine the trace organic compounds in real-world environmental matrices,
      and the results were compared with the results of the conventional liquid-liquid
      extraction method. For the analysis of high-volume water samples, UA-LLSE is a
      simple, inexpensive, time-saving (20 min for 10 L of water sample) and
      environmentally friendly method (reduction in solvent usage), with high
      extraction efficiency (over 90% average recoveries) and excellent precision
      (lower than 7% relative standard deviation, RSD). Most importantly, it is an
      ideal on-site pre-treatment technique for the in situ extraction of trace organic
      compounds in high-volume water matrices.

PMID- 30113044
TI  - Integrating molecular probes and molecular dynamics to reveal binding modes of
      GLUT5 activatory and inhibitory ligands.
AB  - Fructose transporter GLUT5 is characterized by unusual substrate specificity and
      is linked to a variety of metabolic disorders. A series of high-affinity GLUT5
      specific sugar-based probes - ManCous - have been very recently described and
      efficiently used as reporters of GLUT5 activity in cells. Here we present several
      1 microsecond molecular dynamics (MD) simulations of GLUT5 and its complexes with
      fructose and two different ManCou probes, in a solvated cell membrane
      environment. These simulations show key molecular interactions within GLUT5 that
      promote the passage of the substrate through vs. blockage of the transport
      mechanism. Identification of these specific interactions and their long-range
      effects on GLUT5 structure and dynamics provides an essential basis for the
      future development of GLUT5-specific inhibitors.

PMID- 30113045
TI  - Formation of a bi-rhodium boron tube Rh2B18 and its great CO2 capture ability.
AB  - The geometries, bonding and abilities for CO2 capture of the doubly rhodium-doped
      boron cluster Rh2B18 are presented. DFT calculations using the TPSSh functional
      show that the doubly doped Rh2B18 is stable in a high symmetry shape (D9d) in
      which two Rh dopants are vertically and oppositely coordinated to nonagonal faces
      of a (2 * 9) double ring B18 tube, having the form of a teetotum toy. Bonding of
      the tube is analysed using different schemes for partition of total electron
      density (EDI_D, AIM). The high thermodynamic stability of Rh2B18 can be
      rationalized in terms of its electron distribution in which both Rh atoms share
      delocalized bonds with B atoms. Molecular dynamic simulations also confirm its
      stability within a range of temperatures. Exploration of the interaction of gas
      phase CO2 molecules with Rh2B18 suggests that this tubular structure has a great
      ability for capture and transformation of carbon dioxide. Formation of two new
      strong bonds of CO2 with the B-B edges of Rh2B18 favour its capture through a
      dissociative adsorption mechanism in which a nearly spontaneous dissociation of
      CO2 into CO and BO groups follows its attachment.

PMID- 30113046
TI  - Dual-mode infrared laser-excited synergistic effect in NaGdF4:Er3+ nano-glass
      ceramics: a kinetic model.
AB  - Realization of the absorption and conversion of wide band infrared light have
      been a challenge in the field of upconversion luminescence. Herein, a facile
      physical approach is reported to realize the cooperative absorption and
      conversion of dual-band infrared light by NaGdF4:Er3+ nano-glass ceramics by
      employing a dual-mode excitation source (980 nm + 1545 nm). A synergistic effect
      of infrared photons induced by dual-wavelength infrared excitation is observed.
      The dual-mode excited red emission intensity is 2.76 times the total red emission
      intensities from 980 nm and 1545 nm single excitation. This upconversion
      synergistic effect can be modulated by adjusting the single excitation power, and
      it is proved to originate from ground and excited state absorption, in which the
      Er3+ ions in metastable states excited by 980 nm (or 1545 nm) photons are excited
      again by the 1545 nm (or 980 nm) infrared photons. A rate equation model is
      established to simulate the dynamic process in the dual-mode infrared
      upconversion process. The synergistic effect provides us with a way to convert
      two low-energy infrared photons into middle-energy visible photons to enhance the
      upconversion efficiency of rare earth ion doped glass ceramics.

PMID- 30113047
TI  - H2 reduction of Gd- and Sm-doped ceria compared to pure CeO2 at high
      temperatures: effect on structure, oxygen nonstoichiometry, hydrogen solubility
      and hydroxyl chemistry.
AB  - The effect of Gd- and Sm-doping on pure CeO2 with respect to crystal structure,
      oxygen nonstoichiometry, hydrogen solubility and hydroxyl chemistry in a hydrogen
      atmosphere at elevated temperatures was studied using a combination of powder X
      ray diffraction (XRD), temperature-programmed methods (such as reduction,
      desorption and oxidation), and Fourier-Transform Infrared Spectroscopy (FT-IR).
      In particular, Gd0.1Ce0.9O2-delta (GDC10) and Sm0.15Ce0.85O2-delta (SDC15) were
      compared to pure CeO2. After H2 reduction of GDC10/SDC15/CeO2 at 900  degrees C,
      two distinct phases form, which differ from each other in terms of oxygen
      nonstoichiometry. One phase is only slightly reduced and maintains a cubic
      fluorite unit cell. The other phase is strongly oxygen depleted and changes its
      lattice to triclinic. Enrichment or depletion of the dopants in the two phases
      upon reduction was not observed. No evidence for a long-range ordered cerium
      hydride could be found, despite the fact that all samples clearly incorporate
      hydrogen during the reduction procedure. Generally, the treatment of all three
      samples with flowing H2 at 700  degrees C, 800  degrees C and 900  degrees C
      causes the oxygen deficiency and the amount of bound hydrogen to increase with
      reduction temperature. Acceptor doping, thus, promotes hydrogen incorporation,
      but it at the same time decreases the amount of reactive oxygen. In conclusion,
      the study of hydroxyl chemistry shows that doping CeO2 with Gd or Sm creates
      binding sites for reactive hydroxyl groups that are not observed for pure CeO2.
      The distinct infrared absorption peak at ca. 2127 cm-1 - which originates from an
      electronic transition of Ce3+ (2F5/2 -> 2F7/2) - is a viable indicator for the
      reduction degree of all three specimens.

PMID- 30113051
TI  - Metabolic and genetic response to probiotics supplementation in patients with
      diabetic nephropathy: a randomized, double-blind, placebo-controlled trial.
AB  - This study was carried out to evaluate the effects of probiotics administration
      on the metabolic and genetic profiles in patients with diabetic nephropathy (DN).
      This was a randomized, placebo-controlled clinical trial with homeostasis model
      of assessment-estimated insulin resistance (HOMA-IR) as the primary and other
      metabolic profiles, and biomarkers of inflammation and oxidative stress as the
      secondary outcomes. This randomized, double-blind, placebo-controlled clinical
      trial was performed on 60 patients with DN. The patients were randomly assigned
      into two groups to receive either 8 * 109 CFU day-1 probiotic supplements or
      placebo (n = 30 in each group) for 12 weeks. Fasting blood was collected at the
      baseline and end of intervention to measure glycemic control, lipid profiles,
      biomarkers of inflammation and oxidative stress. Multiple linear regression
      models were used to assess the treatment effects on the outcomes adjusting for
      confounding variables. Probiotics supplementation, compared with the placebo,
      resulted in a significant reduction in fasting plasma glucose (P = 0.01), serum
      insulin concentrations (P = 0.01) and HOMA-IR (P = 0.007), and a significant
      increase in the quantitative insulin sensitivity check index (P = 0.04).
      Additionally, compared with the placebo, probiotic intake resulted in a
      significant reduction in triglycerides (P = 0.001) and total-/HDL-cholesterol
      ratio (P < 0.001), and a significant increase in HDL-cholesterol levels (P <
      0.001). Supplementation with probiotics, compared with the placebo, was
      associated with a significant reduction in high-sensitivity C-reactive protein (P
      = 0.001), malondialdehyde (P < 0.001) and advanced glycation end products (P <
      0.001), and a significant elevation in plasma total glutathione (P < 0.001).
      Overall, our study indicated that probiotics supplementation had beneficial
      effects on glycemic control and markers of cardio-metabolic risk.

PMID- 30113052
TI  - Metal vapor synthesis of ultrasmall Pd nanoparticles functionalized with N
      heterocyclic carbenes.
AB  - The synthesis of N-heterocyclic carbene (NHC)-stabilized palladium nanoparticles
      (PdNPs) by an entirely new strategy comprising the NHC functionalization of
      ligand-free PdNPs obtained by metal vapor synthesis is described. Detailed
      characterization confirms the formation of very small monodisperse PdNPs (2.3 nm)
      and the presence of the NHC ligand on the Pd surface. The stable NHC
      functionalized PdNPs dispersed onto a carbon support showed high activity in the
      hydrogenation of limonene with enhanced regioselectivity in comparison to bare
      PdNPs on carbon.

PMID- 30113053
TI  - CBS extrapolation in electronic structure pushed to the end: a revival of minimal
      and sub-minimal basis sets.
AB  - The complete basis set (CBS) limit is secluded in calculations of electronic
      structure, and hence CBS extrapolation draws immediate attention. Of the highest
      importance is the extremely slow-convergent correlation energy as obtained both
      from Moller-Plesset perturbation theory (MP2) and the gold standard coupled
      cluster singles, doubles, and perturbative triples method [CCSD(T)], both picked
      as the focal point. Because today's massive electronic structure calculations
      demand schemes for CBS extrapolation from the lowest rungs of the hierarchical
      staircase, the focus is also on how minimal and subminimal basis sets can help in
      the endeavour. The above has prompted, for the first time, the development of a
      reliable analytic variant of the unified singlet- and triplet-pair extrapolation
      (USTE) scheme, which is next utilized to hierarchize any arbitrary basis set.
      With all available basis set families for molecular orbital calculations
      systematized as subminimal, minimal and extended from the fraction of correlation
      energy that they can recover, the full approach is simple and general, yet
      reliable, and hereby illustrated for basis sets as small as Huzinaga MINI and as
      extended as the sophisticated ansatzes that are utilized in modern explicitly
      correlated MP2-F12 and CCSD(T)-F12 calculations. Extensively tested with up to 26
      basis sets from various families, the reported results show that CBS
      extrapolation from a (subminimal, extended) basis-set pair yields correlation
      energies that outperform by far those obtained from Kohn-Sham density functional
      theory (KS DFT). When employing two subminimal basis sets, the results may still
      outperform KS-DFT but at a drastically smaller computational cost. To further
      gauge its performance, the new method is utilized to calculate the energies of
      all 45 isomers of C8H8 recently reported at a high ab initio level, with the
      present results showing excellent agreement with the available data. The present
      cost-effective approach may therefore be expected to have a broad impact on
      chemistry and even materials science.

PMID- 30113054
TI  - Carbonate: an alternative dopant to stabilize new perovskite phases; synthesis
      and structure of Ba3Yb2O5CO3 and related isostructural phases Ba3Ln2O5CO3 (Ln =
      Y, Dy, Ho, Er, Tm and Lu).
AB  - In this paper we report the synthesis of the new layered perovskite oxide
      carbonate, Ba3Yb2O5CO3. This phase is formed when 3BaCO3 : 1Yb2O3 mixtures are
      heated in air at temperatures <=1000  degrees C, while above this temperature the
      carbonate is lost and the simple oxide phase Ba3Yb4O9 is observed. The structure
      of Ba3Yb2O5CO3 was determined from neutron diffraction studies and consists of a
      tripled perovskite with double Yb-O layers separated by carbonate layers, the
      first example of a material with such a structure. Further studies showed that
      analogous Ba3Ln2O5CO3 phases could be formed for other rare earths (Ln = Y, Dy,
      Ho, Er, Tm and Lu). The results highlight the ability of the perovskite structure
      to accommodate carbonate groups, and emphasise the need to consider their
      potential presence particularly for perovskite systems prepared in lower
      temperature synthesis routes.

PMID- 30113055
TI  - Two-component supramolecular metallogels with the presence of Pt-Pt metal-metal
      interactions.
AB  - Two-component supramolecular metallogels have been successfully constructed with
      the involvement of heteromeric Pt(ii)Pt(ii) metal-metal interactions, which
      display low-energy emissions in the near-infrared region. We demonstrate and
      rationalize how the gel stability can be increased by modulating the gelation
      solvent as well as the crosslinking unit.

PMID- 30113056
TI  - Tunable photoluminescence in a van der Waals heterojunction built from a MoS2
      monolayer and a PTCDA organic semiconductor.
AB  - We report the photoluminescence (PL) characteristics of a van der Waals (vdW)
      heterojunction constructed by simply depositing an organic semiconductor of
      3,4,9,10-perylene tetracarboxylic dianhydride (PTCDA) onto a two-dimensional MoS2
      monolayer. The crystallinity of PTCDA on MoS2 is significantly improved due to
      the vdW epitaxial growth. We observe an enhanced PL intensity and PL peak shift
      of the MoS2/PTCDA heterojunction compared with the solo MoS2 and PTCDA layer. The
      synergistic PL characteristics are believed to originate from the hybridization
      interaction between the MoS2 and the PTCDA as evidenced by density functional
      theory calculations and Raman measurements. The hybridization interfacial
      interaction is found to be greatly influenced by the crystalline ordering of the
      PTCDA film on the 2D MoS2. Our study opens up a new avenue to tune the PL of vdW
      heterojunctions consisting of TMDs and organic semiconductors for optoelectronic
      applications.

PMID- 30113061
TI  - Shape-dependent thermo-plasmonic effect of nanoporous gold at the nanoscale for
      ultrasensitive heat-mediated remote actuation.
AB  - Nanoporous gold (NPG) promises efficient light-to-heat transformation, yet
      suffers limited photothermal conversion efficiency owing to the difficulty in
      controlling its morphology for the direct modulation of thermo-plasmonic
      properties. Herein, we showcase a series of shape-controlled NPG nanoparticles
      with distinct bowl- (NPG-B), tube- (NPG-T) and plate-like (NPG-P) structures for
      quantitative temperature regulation up to 140  degrees C in <1 s using laser
      irradiation. Notably, NPG-B exhibits the highest photothermal efficiency of 68%,
      which is >12 and 39 percentage points better than those of other NPG shapes (NPG
      T, 56%; NPG-P, 49%) and Au nanoparticles (29%), respectively. We attribute NPG
      B's superior photothermal performance to its >13% enhanced light absorption cross
      section compared to other Au nanostructures. We further realize an ultrasensitive
      heat-mediated light-to-mechanical "kill switch" by integrating NPG-B with a heat
      responsive shape-memory polymer (SMP/NPG-B). This SMP/NPG-B hybrid is analogous
      to a photo-triggered mechanical arm, and can be activated swiftly in <4 s simply
      by remote laser irradiation. Achieving remotely-activated "kill switch" is
      critical in case of emergencies such as gas leaks, where physical access is
      usually prohibited or dangerous. Our work offers valuable insights into the
      structural design of NPG for optimal light-to-heat conversion, and creates
      opportunities to formulate next-generation smart materials for on-demand and
      multi-directional responsiveness.

PMID- 30113062
TI  - Synthesis and application of a new chiral monodentate spiro phosphoramidite
      ligand based on hexamethyl-1,1'-spirobiindane backbone in asymmetric
      hydroamination/arylation of alkenes.
AB  - The design and synthesis of a new chiral monodentate spiro phosphoramidite ligand
      based on a hexamethyl-1,1'-spirobiindane scaffold has been accomplished. The
      ligand could serve as an elegant chiral monodentate ligand in the Pd-catalyzed
      asymmetric hydroamination/arylation of alkenes leading to chiral imidazolidin-2
      ones with good enantioselectivities.

PMID- 30113063
TI  - High-performance asymmetric supercapacitors based on monodisperse MnO
      nanocrystals with high energy densities.
AB  - Monodisperse spherical MnO nanocrystals (NCs) with a size of 22.5 nm were
      synthesized by the thermal decomposition of manganese oleate in the presence of
      oleic acid and 1-octadecene. The as-synthesized MnO NCs show superior
      electrochemical performances with a specific capacitance of 736.4 F g-1 at a
      current density of 1 A g-1 and retain 93.3% of initial specific capacitance after
      5000 cycles. The MnO NC electrode was successfully assembled in an asymmetric
      supercapacitor as the cathode with an activated carbon (AC) electrode as the
      anode. The as-fabricated device can demonstrate remarkable performance with an
      energy density of 44.2 W h kg-1, a power density of 900 W kg-1, and excellent
      cycling stability. This work provides a new direction for MnO nanomaterials
      towards high-performance energy storage devices.

PMID- 30113065
TI  - Turning intercalators into groove binders: synthesis, photophysics and DNA
      binding properties of tetracationic mononuclear ruthenium(ii)-based chromophore
      quencher complexes.
AB  - The synthesis of two new tetracationic mononuclear RuII complexes containing the
      tetrapyridyl [3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine ligand in which the
      uncoordinated site has been converted into a dicationic ethylene-bipyridyldiylium
      unit is reported. The structure of the complexes is fully assigned through
      detailed NMR studies and, in one case, through an X-ray crystallography study.
      Voltammetry, optical spectroscopy and computational studies confirm that the
      bipyridyldiylium moiety has a low-lying reduction that quenches the 3MLCT-based
      emission usually observed in such systems. The new complexes interact with DNA in
      a quite different manner to their dicationic analogues: they both bind to duplex
      DNA with micromolar affinity through groove binding. These observations are
      rationalized through a consideration of their structural and electronic
      properties.

PMID- 30113066
TI  - Idiopathic histiocytoid Sweet syndrome: a case report with clinical and
      histopathological considerations.
AB  - BACKGROUND: Histiocytoid Sweet syndrome is characterized by a predominant
      neutrophilic dermal infiltrate. Usual clinical differential diagnosis includes
      erythema multiforme, drug eruption, and erythema nodosum. Histiocytoid Sweet
      syndrome is considered an uncommon histopathological variant of the disease.
      METHODS: We evaluated clinical, histopathological, and immunohistochemical
      findings of a case categorized as idiopathic histiocytoid Sweet syndrome in which
      clinical-epidemiological data raised the possibilities of Sweet syndrome,
      leprosy, and drug reaction. RESULTS: Positive reaction to myeloperoxidase (MPO)
      in histiocytoid cells of the dermal infiltrate, response to oral corticosteroids,
      clinical and laboratory investigation, and absence of cutaneous lesions or
      clinical complaints within 1 year of follow-up are consistent with the diagnosis
      of idiopathic histiocytoid Sweet syndrome. CD68 (PG-M1) and CD15 positive cells
      were also present among dermal cells. CONCLUSIONS: Epidemiological data are
      relevant while considering a clinical differential diagnosis of Sweet syndrome
      that can be further expanded, from a histopathological point of view, when
      dealing with the histiocytoid variant since neutrophils, macrophages, and
      immature myelomonocytic cells with histiocytoid morphology are present. The
      significance of the MPO positive mononuclear dermal cells are not completely
      established.

PMID- 30113067
TI  - Limiting Respiratory Viral Infection by Targeting Antiviral and Immunological
      Functions of BST-2/Tetherin: Knowledge and Gaps.
AB  - Recent findings regarding the cellular biology and immunology of BST-2 (also
      known as tetherin) indicate that its function could be exploited as a universal
      replication inhibitor of enveloped respiratory viruses (e.g., influenza,
      respiratory syncytial virus, etc.). BST-2 inhibits viral replication by
      preventing virus budding from the plasma membrane and by inducing an antiviral
      state in cells adjacent to infection via unique inflammatory signaling
      mechanisms. This review presents the first comprehensive summary of what is
      currently known about BST-2 anti-viral function against respiratory viruses, how
      these viruses construct countermeasures to antagonize BST-2, and how BST-2
      function might be targeted to develop therapies to treat respiratory virus
      infections. The authors address the current gaps in knowledge, including the need
      for mechanistic understanding of BST-2 antagonism by respiratory viruses, that
      should be bridged to achieve that goal.

PMID- 30113069
TI  - Neuronal response properties across cytochrome oxidase stripes in primate V2.
AB  - Cytochrome oxidase histochemistry reveals large-scale cortical modules in area V2
      of primates known as thick, thin, and interstripes. Anatomical,
      electrophysiological, and tracing studies suggest that V2 cytochrome oxidase
      stripes participate in functionally distinct streams of visual information
      processing. However, there is controversy whether the different V2 compartments
      indeed correlate with specialized neuronal response properties. We used multiple
      electrode arrays (16 * 2, 8 * 4 and 4 * 4 matrices) to simultaneously record the
      spiking activity (N = 190 single units) across distinct V2 stripes in
      anesthetized and paralyzed capuchin monkeys (N = 3 animals, 6 hemispheres).
      Visual stimulation consisted of moving bars and full-field gratings with
      different contrasts, orientations, directions of motion, spatial frequencies,
      velocities, and color contrasts. Interstripe neurons exhibited the strongest
      orientation and direction selectivities compared to the thick and thin stripes,
      with relatively stronger coding for orientation. Additionally, they responded
      best to higher spatial frequencies and to lower stimulus velocities. Thin stripes
      showed the highest proportion (80%) of neurons selective to color contrast
      (compared to 47% and 21% for thick and interstripes, respectively). The great
      majority of the color selective cells (86%) were also orientation selective.
      Additionally, thin stripe neurons continued to increase their firing rate for
      stimulus contrasts above 50%, while thick and interstripe neurons already
      exhibited some degree of response saturation at this point. Thick stripes best
      coded for lower spatial frequencies and higher stimulus velocities. In
      conclusion, V2 CytOx stripes exhibit a mixed degree of segregation and
      integration of information processing, shedding light into the early mechanisms
      of vision.

PMID- 30113068
TI  - S,S-Chiral Linker Induced U Shape with a Syn-facial Sensitizer and Photocleavable
      Ethene Group.
AB  - There is a major need for light-activated materials for the release of
      sensitizers and drugs. Considering the success of chiral columns for the
      separation of enantiomer drugs, we synthesized an S,S-chiral linker system
      covalently attached to silica with a sensitizer ethene near the silica surface.
      First, the silica surface was modified to be aromatic rich, by replacing 70% of
      the surface groups with (3-phenoxypropyl)silane. We then synthesized a 3
      component conjugate [chlorin sensitizer, S,S-chiral cyclohexane and ethene
      building blocks] in 5 steps with a 13% yield, and covalently bound the conjugate
      to the (3-phenoxypropyl)silane-coated silica surface. We hypothesized that the
      chiral linker would increase exposure of the ethene site for enhanced 1 O2 -based
      sensitizer release. However, the chiral linker caused the sensitizer conjugate to
      adopt a U shape due to favored 1,2-diaxial substituent orientation; resulting in
      a reduced efficiency of surface loading. Further accentuating the U shape was pi
      pi stacking between the (3-phenoxypropyl)silane and sensitizer. Semiempirical
      calculations and singlet oxygen luminescence data provided deeper insight into
      the sensitizer's orientation and release. This study has lead to insight on
      modifications of surfaces for drug photorelease and can help lead to the
      development of miniaturized photodynamic devices.

PMID- 30113071
TI  - Collaborative challenges in the use of telecare.
AB  - INTRODUCTION: As a growing number of seniors with complex needs are living at
      home, the implementation of telecare has become a priority. This article aims to
      identify factors influencing inter- and intra-organisational collaboration in
      Norwegian primary care. The focus is on collaboration in service provision for
      senior users with telecare solutions, in this case personal alarms. METHODS: Data
      were collected from two individual interviews with each of seven middle managers
      from four different units. Additionally, group interviews were conducted during
      two workshops, both with 16 and 17 front-line staff members from four local
      authority units. RESULTS: Challenges and barriers to collaboration and
      integration were information flow and information sharing, unclear understanding
      of the division of duties between the units involved and their employees and the
      lack of meeting points between the emergency medical centre and home nursing.
      Interagency meetings between the purchasing office and home nursing enhance
      collaboration. CONCLUSION: The introduction of telecare does not simplify
      collaboration or improve services; technology does not solve collaboration
      challenges. Technology limits information to written form, which may not meet the
      needs of the service provider and user. Collaboration and integration require
      common strategies and leadership that implements them, including in telecare.

PMID- 30113070
TI  - PGK1 as an immune target in Kawasaki disease.
AB  - Kawasaki disease (KD) is an immune-mediated vasculitis with symptoms that mimic
      febrile illness; the immune origin has been suggested but never proved. First,
      cell chip technology was used to screen immune targets cells. With the indirect
      immunofluorescence assay we found that the HeLa cell chip could be recognized by
      KD patient serum samples. The target cell proteome was extracted as antigens, and
      antigen recognition reaction was performed using the patients' serum as
      antibodies and the detected target protein was detected and identified as
      phosphoglycerate kinase 1 (PGK1). Then PGK1 was produced and tested with enzyme
      linked immunosorbent assay (ELISA), Western blotting, immunoprecipitation and
      competitive inhibition immunofluorescence assay. Immunoglobulin (Ig)G against
      PGK1 was detected in 46% (23 of 50) sera of KD patients, 13% (five of 38) sera in
      febrile non-KD patients (FC) and 2.6% (one of 38) sera in healthy donors. As an
      immune target, PGK1 not only helps understanding of the pathogenesis, it also has
      potential value in facilitating the laboratory diagnosis of KD.

PMID- 30113072
TI  - Chromoblastomycosis: clinical experience and review of literature.
AB  - BACKGROUND: Chromoblastomycosis is a tropical chronic infectious dermatosis
      characterized by the moriform bodies. To review all cases of chromoblastomycosis
      attended in the reference service of dermatology. METHODS: Series of cases of
      chromoblastomycosis attended in a dermatology reference service. Through an
      integrated system search of assistance, based on CID-10 B43, we reviewed
      epidemiological and comorbidities data, clinical presentations, treatments, and
      outcomes of each clinical case. RESULTS: From 2011 to 2017, we had five new cases
      of chromoblastomycosis. The average age was 65.6 years. All of them were men. One
      patient was HIV-positive, and another patient was immunosuppressed by the use of
      mycophenolate mofetil and prednisone due to renal transplant. Two patients had no
      history of evident trauma. The time between onset of symptoms and diagnosis
      ranged from 7 to 600 months. Fonsecaea pedrosoi was the isolated fungi. All cases
      were formally confirmed. Itraconazole with or without other therapies was
      effective in all cases. CONCLUSIONS: We report five never reported cases of
      chromoblastomycosis, and we review the clinical experience in diagnosis and
      treatment of chromoblastomycosis, an infrequent and neglected subcutaneous
      mycosis.

PMID- 30113073
TI  - Risk of endometrial cancer and endometrial hyperplasia with atypia in
      asymptomatic postmenopausal women with endometrial thickness >=11 mm: A
      systematic review and meta-analysis.
AB  - PURPOSE: To evaluate the risk of endometrial cancer and/or endometrial
      hyperplasia with atypia in asymptomatic postmenopausal women with endometrial
      thickness >= 11 mm. METHODS: Systematic review of literature using database
      search (PubMed and Web of Science) of articles published between January 1990 and
      December 2016 evaluating the correlation between endometrial thickness as
      measured by transvaginal ultrasound (double layer) and histopathological findings
      in asymptomatic postmenopausal women, using the following terms: "endometrial
      thickness," "postmenopausal," "postmenopause," and "asymptomatic." Inclusion
      criteria were prospective or retrospective studies of more than 150 cases that
      provided information on endometrial thickness and its correlation with
      histopathological data. Studies that included patients with hormone replacement
      therapy, tamoxifen, or aromatase inhibitors were excluded. The overall relative
      risk (RR) for EC/EHA was calculated, stratifying the patients into two groups
      according to endometrial thickness (<11 mm and >=11 mm). Heterogeneity was
      assessed by calculating I2 . RESULTS: The search identified 289 studies. After
      exclusions, nine articles that met all the inclusion criteria were included,
      comprising data from 4751 women. The prevalence of endometrial cancer and/or
      endometrial hyperplasia with atypia was 2.4%. The relative risk of endometrial
      cancer and/or endometrial hyperplasia with atypia in the >=11 mm group was 2.59
      (95% CI: 1.66-4.05). High heterogeneity was observed between studies (I2 : 57.3%,
      P = .016). CONCLUSIONS: Overall the risk for EC/EHA was 2.6 times greater in
      women with ET >=11 mm vs women with ET 5-10 mm, although there was significant
      heterogeneity in estimates across studies.

PMID- 30113074
TI  - Influence of light on lignin-degrading activities of fungal genus Polyporus s.
      str.
AB  - Six strains belonging to five species of Polyporus (P. arcularius, P.
      arcularioides, P. tricholoma, P. cfr. tricholoma, and P. varius), collected from
      an Atlantic Forest area in Misiones (Argentina), where species usually grow
      exposed to high temperatures and humidity, were identified by morphological and
      molecular analyses. P. tricholoma (BAFC 4536) and P. arcularioides (BAFC 4534)
      were selected by their lignin-degrading enzyme production, their ability to
      produce primordial of basidiomes under submerged fermentation, and the decrease
      in lignin content caused in Poplar wood (up to 29% after 45 days). Among several
      variables evaluated with a Plackett-Burman design (glucose, copper, vanillic acid
      and manganese concentration, incubation period, and light incidence), the most
      important factor affecting laccase and Mn-peroxidase (MnP) production by both
      strains, was light incidence. Light induced fruit body development but diminished
      laccase and MnP production. Moreover, a modified isoenzymatic laccase pattern was
      observed, showing additional isoenzymes when fungi were cultivated under darkness
      and differences in optimal temperature. Although the studied strains did not
      produce high laccase and MnP titers (uppermost detected 4230 and 90 U L-1 ,
      respectively), their laccases showed thermal stability and optimal temperature
      above 70  degrees C, representing an interesting source in the search of thermo
      tolerant enzymes for biotechnological applications.

PMID- 30113075
TI  - Is this the time to reconsider the names for xenobiotic nuclear receptors?
AB  - Pregnane X receptor (PXR) has been known as a xenobiotic nuclear receptor and
      transcriptional factor that is important for inducing the expression of genes
      involved in drug disposition (1, 2). Recently, PXR has emerged to critically
      regulate endobiotic metabolism, including the homeostasis of glucose, lipids,
      steroids, bile acids, bilirubin, retinoids and bone minerals, and maybe
      implicated in the treatment of cholestasis, inflammatory bowel disease, and
      nonalcoholic fatty liver diseases (3). PXR activation is also well known to
      increase liver size and cause liver hypertrophy. However, only a few studies have
      explored the role of PXR in liver regeneration and regrowth (4, 5), moreover, the
      exact mechanism by which PXR induces liver growth, especially how PXR interacts
      with the machinery of cellular proliferation, remains unclear. This article is
      protected by copyright. All rights reserved.

PMID- 30113076
TI  - Migraine and Non-Migraine Headaches Following Diagnostic Catheter-Based Cerebral
      Angiography.
AB  - BACKGROUND AND OBJECTIVE: No reliable estimates of headaches following catheter
      based cerebral angiography are available. We performed an observational cohort
      study to ascertain the frequency and type of headaches following catheter-based
      cerebral angiography. MATERIALS AND METHODS: Consecutive patients who underwent
      cerebral angiography through the transfemoral (or infrequently radial) route were
      included. Each patient underwent a brief neurological assessment after the
      procedure and more detailed assessment was performed if any patient reported
      occurrence of a headache. The headaches were classified as migraine if the
      diagnostic criteria specified by International Headache Society were met. The
      headache severity was classified using a visual numeric rating scale and time to
      reach pain free status for 2 consecutive hours was ascertained. RESULTS: Migraine
      headaches occurred in 5 (3.1%, 95% confidence interval [CI] 1.0-7.2%) of 158
      patients who underwent cerebral angiography. The median severity of migraine
      headaches was 10/10 and time to resolution of headaches was 120 minutes (range 60
      360 minutes). Migraine headaches occurred in 4 (18.1%, 95% CI 5.2-40.3%) of 22
      patients with a history of migraine and 4 (23.5%, 95% CI 6.8-50%) of 17 patients
      with regular migraine headaches (>=1 episodes per month). Headaches occurred in 6
      (3.8%, 95% CI 1.8-8.0%) patients who did not meet the criteria for migraine
      headaches. CONCLUSIONS: We provide occurrence rates of migraine headaches, an
      under-recognized adverse event, in patients undergoing catheter-based cerebral
      angiography.

PMID- 30113077
TI  - Optimization of a reduced volume PCR amplification for PowerPlex(r) Fusion kit
      using FTATM cards and generation of population genetic data for Brunei
      population.
AB  - The commercial PowerPlex(r) Fusion kit is an autosomal STR multiplex kit that has
      high discrimination power and is more informative in forensic, paternity, and
      relationship-testing cases. Key features of this multiplex system are the
      possibility to direct amplify FTATM card punches as well as non-FTA cards and
      commonly used swabs; optimised inhibitor tolerance and high sensitivity
      generating full profiles from amount as little as 100 pg of human DNA. This study
      focused on the optimization of performance variables such as FTATM punch sizes,
      reduced reaction volumes, and FTATM purification reagent aiming to increase the
      analytical sensitivity, decrease the sample consumption, and cost effectiveness.
      LOD and LOQ values demonstrated high sensitivity of the PowerPlex(r) Fusion
      system. In addition, population databases of Brunei Malay and Chinese from the
      Brunei Darussalam were established, and parameters of forensic importance were
      calculated. Overall, the forensic parameters indicated an enhanced utility of the
      PowerPlex(r) Fusion kit for forensic evidence analysis and paternity testing in
      Brunei Malay and Chinese populations.

PMID- 30113078
TI  - Evolving systems biology approaches to understanding non-coding RNAs in pulmonary
      hypertension.
AB  - Our appreciation of the roles of non-coding RNAs, in particular microRNAs, in the
      manifestation of pulmonary hypertension (PH) has advanced considerably over the
      past decade. Comprised of small nucleotide sequences, microRNAs have demonstrated
      critical and broad regulatory roles in the pathogenesis of PH via the direct
      binding to messenger RNA transcripts for degradation or inhibition of
      translation, thereby exerting a profound influence on cellular activity. Yet, as
      inherently pleiotropic molecules, microRNAs have been difficult to study using
      traditional, reductionist approaches alone. With the advent of high-throughput 
      omics technologies and more advanced computational modelling, the study of
      microRNAs and their multi-faceted and complex functions in human disease serves
      as a fertile platform for the application of systems biology methodologies in
      combination with traditional experimental techniques. Here, we offer our
      viewpoint of past successes of systems biology in elucidating the otherwise
      hidden actions of microRNAs in PH, as well as areas for future development to
      integrate these strategies into the discovery of RNA pathobiology in this
      disease. We contend that such successful applications of systems biology in
      elucidating the functional architecture of microRNA regulation will further
      reveal the molecular mechanisms of disease, while simultaneously revealing
      potential diagnostic and therapeutic strategies in disease amelioration.

PMID- 30113079
TI  - SLIT with house dust mite tablets in children - the evidence based journey of AIT
      proceeds.

PMID- 30113080
TI  - Transposons: the agents of antibiotic resistance in bacteria.
AB  - Transposons are a group of mobile genetic elements that are defined as a DNA
      sequence. Transposons can jump into different places of the genome; for this
      reason, they are called jumping genes. However, some transposons are always kept
      at the insertion site in the genome. Most transposons are inactivated and as a
      result, cannot move. Transposons are divided into two main groups:
      retrotransposons (class I) and DNA transposons (class II). Retrotransposons are
      often found in eukaryotes. DNA transposons can be found in both eukaryotes and
      prokaryotes. The bacterial transposons belong to the DNA transposons and the Tn
      family, which are usually the carrier of additional genes for antibiotic
      resistance. Transposons can transfer from a plasmid to other plasmids or from a
      DNA chromosome to plasmid and vice versa that cause the transmission of
      antibiotic resistance genes in bacteria. The treatment of bacterial infectious
      diseases is difficult because of existing antibiotic resistance that part of this
      antibiotic resistance is caused by transposons. Bacterial infectious diseases are
      responsible for the increasing rise in world mortality rate. In this review,
      transposons and their roles have been studied in bacterial antibiotic resistance,
      in detail.

PMID- 30113081
TI  - Mobile phone-based UV fluorescence microscopy for the identification of fungal
      pathogens.
AB  - BACKGROUND AND OBJECTIVE: Dermatophytes are fungi that cause infections in hair,
      skin, and nails. Potassium Hydroxide (KOH) microscopy is the most frequently used
      method for identifying dermatophytes. KOH helps in the visualization of the
      hyphae as it clears the debris present in the specimen but needs a trained eye
      for final diagnosis of the infection. Fluorescence microscopy using staining
      agents, such as calcofluor white (CFW) or blankophor, is a better method for
      identification of dermatophytes but is not used in clinics due to the cost and
      complexity of fluorescence microscopes. The objective of the present work is to
      develop a simple low-cost mobile phone-based device for the identification of
      fungal pathogens in skin samples. MATERIALS AND METHODS: A fluorescence
      spectrometer was used to establish the excitation/emission peaks of fluorescence
      intensity of CFW and KOH and Methyl Cellulose, a surrogate of fungi used for
      system development. A transillumination microscopy prototype was fabricated using
      off-the-shelf components, 3D printing and a mobile phone. The system was
      optically characterized using contrast resolution targets and verified using
      fungi isolate samples. An isolate of Trichophyton (T) rubrum was grown for 10-14
      days for formation of fungal colonies. The surface of a single colony was gently
      scraped with a sterile loop and transferred to a glass slide. CFW with KOH was
      added to the T. rubrum and covered with cover slip for microscopic examination.
      The images of T. rubrum obtained with the prototype device were compared to those
      obtained using a commercial microscope. RESULTS: The excitation/emission
      wavelength pair for CFW was found to be 370/430 nm. The proposed device design is
      a transillumination microscopy setup using a mobile phone. It consists of a 365
      nm LED as the excitation source, a 3V battery to power the LED, a slide to hold
      the sample, a lens for magnification and a phone to capture and store the images
      of the sample. The fabricated prototype has a resolution of 70 to 99 um, a 2% to
      30% distortion, and 60% contrast value for well illuminated samples. Images of T.
      rubrum samples obtained under brightfield illumination clearly show the long
      septate hyphae of the dermatophyte. As expected, images of the same samples with
      CFW and KOH show blue fluorescence, which results from the binding of the CFW to
      the chitin and cellulose in the fungal hyphae. These images are similar to those
      obtained with a commercial microscope. SUMMARY AND CONCLUSIONS: The concept and
      design of a mobile phone-based fluorescence microscope to identify dermatophytes
      has been demonstrated in a prototype and laboratory samples. The concept and
      design offer a simple, low-cost, compact but robust method for identification of
      fungal pathogens. This method is shown to be feasible for detecting fluorescence
      accurately and imaging the fungal structure at a resolution of 100 um or better.
      Lasers Surg. Med. (c) 2018 Wiley Periodicals, Inc.

PMID- 30113082
TI  - Pathogens and autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a severe form of hepatitis resulting in the
      autoimmune-mediated destruction of the liver parenchyma. Whereas many of the
      immunopathogenic events have been elucidated and some of the drivers of the
      disease have been identified, little is known about the aetiology of the disease.
      There are certain risk factors, such as particular human leucocyte antigen (HLA)
      haplotypes, that enhance the susceptibility for AIH or influence the severity of
      the disease. However, as for many other autoimmune diseases, the mere presence of
      such risk factors does not warrant the occurrence of the disease. Not all
      individuals carrying risk factors develop AIH, and not all patients with AIH are
      carriers of high-risk alleles. Thus, additional environmental factors need to be
      considered as triggers for AIH. Environmental factors include diet, sunlight
      exposure, stress, medication and hygiene, as well as pathogen infections and
      vaccinations. This review discusses if pathogens should be considered as triggers
      for the initiation and/or propagation of AIH.

PMID- 30113083
TI  - Interventions for treating oro-antral communications and fistulae due to dental
      procedures.
AB  - BACKGROUND: An oro-antral communication is an unnatural opening between the oral
      cavity and maxillary sinus. When it fails to close spontaneously, it remains
      patent and is epithelialized to develop into an oro-antral fistula. Various
      surgical and non-surgical techniques have been used for treating the condition.
      Surgical procedures include flaps, grafts and other techniques like re
      implantation of third molars. Non-surgical techniques include allogenic materials
      and xenografts. This is an update of a review first published in May 2016.
      OBJECTIVES: To assess the effectiveness and safety of various interventions for
      the treatment of oro-antral communications and fistulae due to dental procedures.
      SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the
      following databases: Cochrane Oral Health's Trials Register (to 23 May 2018), the
      Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library,
      2018, Issue 4), MEDLINE Ovid (1946 to 23 May 2018), and Embase Ovid (1980 to 23
      May 2018). The US National Institutes of Health Trials Registry
      (ClinicalTrials.gov) and the World Health Organization International Clinical
      Trials Registry Platform were searched for ongoing trials. No restrictions were
      placed on the language or date of publication when searching the electronic
      databases. We also searched the reference lists of included and excluded trials
      for any randomised controlled trials (RCTs). SELECTION CRITERIA: We included RCTs
      evaluating any intervention for treating oro-antral communications or oro-antral
      fistulae due to dental procedures. We excluded quasi-RCTs and cross-over trials.
      We excluded studies on participants who had oro-antral communications, fistulae
      or both related to Caldwell-Luc procedure or surgical excision of tumours. DATA
      COLLECTION AND ANALYSIS: Two review authors independently selected trials. Two
      review authors assessed trial risk of bias and extracted data independently. We
      estimated risk ratios (RR) for dichotomous data, with 95% confidence intervals
      (CI). We assessed the overall quality of the evidence using the GRADE approach.
      MAIN RESULTS: We included only one study in this review, which compared two
      surgical interventions: pedicled buccal fat pad flap and buccal flap for the
      treatment of oro-antral communications. The study involved 20 participants. The
      risk of bias was unclear. The relevant outcome reported in this trial was
      successful (complete) closure of oro-antral communication.The quality of the
      evidence for the primary outcome was very low. The study did not find evidence of
      a difference between interventions for the successful (complete) closure of an
      oro-antral communication (RR 1.00, 95% Cl 0.83 to 1.20) one month after the
      surgery. All oro-antral communications in both groups were successfully closed so
      there were no adverse effects due to treatment failure.We did not find trials
      evaluating any other intervention for treating oro-antral communications or
      fistulae due to dental procedures. AUTHORS' CONCLUSIONS: We found very low
      quality evidence from a single small study that compared pedicled buccal fat pad
      and buccal flap. The evidence was insufficient to judge whether there is a
      difference in the effectiveness of these interventions as all oro-antral
      communications in the study were successfully closed by one month after surgery.
      Large, well-conducted RCTs investigating different interventions for the
      treatment of oro-antral communications and fistulae caused by dental procedures
      are needed to inform clinical practice.

PMID- 30113084
TI  - The influence of sleep disorders on the quality of life in patients with chronic
      low back pain.
AB  - INTRODUCTION: Low back pain (LBP) is one of the most common pain syndromes, and
      its prevalence has increased significantly in the past three decades. OBJECTIVES:
      The aim of this study was to evaluate the effects of insomnia and daytime
      sleepiness on the quality of life (QOL) of patients suffering from chronic back
      pain. MATERIAL AND METHODS: It is a cross-sectional study conducted among 100
      people (aged 25-75 years - mean age 49.53 +/- 10.92) treated in a neurological
      clinic for chronic back pain lasting longer than 3 months. The diagnostic survey
      method was applied for the purposes of this study with the use of: the author's
      questionnaire and standardised questionnaires that is Visual Analogue Scale
      (VAS), Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS) and Polish
      version of WHO Quality of Life-BREF questionnaire (WHOQOL-BREF). The results were
      statistically analysed. RESULTS: Analysis of the study material showed that 83%
      of patients suffered from insomnia (scored 6 or more points on the AIS) and 29%
      experienced mild daytime sleepiness. People who were more sleepy during the day
      were characterised by lower perception of the QOL (r = -0.034, p = 0.029) and
      lower perception of general health (r = -0.035, p = 0.04). Analysis of multiple
      variables (using linear regression) showed that independent predictor of the QOL
      in all domains is the result of the AIS questionnaire (p < 0.05). CONCLUSIONS:
      Sleep disorders - both insomnia and daytime sleepiness - are a common health
      problem experienced by people with LBP. Insomnia is an important predictor
      affecting the QOL in people with LBP.

PMID- 30113085
TI  - Ultrasonography and autopsy correlation of fetal hypoplastic left heart syndrome.
AB  - Hypoplastic left heart syndrome (HLHS) represents a spectrum of abnormalities
      which marks the underdevelopment of left side cardiac structures. We present the
      ultrasound and autopsy correlation of two cases with HLHS with core pathology as
      isolated mitral atresia in one and aortic atresia in another. In both the cases
      after diagnostic confirmation on ultrasound (US), the couple opted for
      termination of pregnancy and consented for autopsy. The correlation of US and
      autopsy images of HLHS, facilitated our understanding of pathology behind the
      image obtained on US. The autopsy not only confirmed the antenatal diagnosis, but
      also added new findings.

PMID- 30113086
TI  - The clinical anatomy of dyspareunia: A review.
AB  - Dyspareunia can be described as continuous unremitting or intermittent pain
      associated with intercourse. It can be classified based on the location of the
      pain - entry or deep dyspareunia, or based on when the pain was first experienced
      - primary or secondary dyspareunia. There are different causes of dyspareunia and
      some of the most important causes include the following: vulvodynia, postpartum
      dyspareunia, endometriosis, inadequate vaginal lubrication or arousal, and other
      anogenital causes such as hemorrhoids and anal fissures. In this review, our
      objective is to apply the anatomical knowledge of dyspareunia to patient care,
      increase awareness among clinicians about the diverse etiology of dyspareunia and
      ensure that the whole patient, not just the pain of dyspareunia is being treated
      as the causes of dyspareunia can be due to various pathologies. Clin. Anat.,
      31:1013-1017, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30113087
TI  - Using the pain principle to provide a new approach to invasive treatments and end
      of-life care.

PMID- 30113088
TI  - Prevalence of musculocutaneous nerve variations: Systematic review and meta
      analysis.
AB  - We aimed to establish the prevalence of the musculocutaneous nerve (MCN)
      variations and the probability of the variation being pure or mixed in the same
      plexus. We applied the principles of evidence-based anatomy to find, appraise,
      and synthesize data through a meta-analysis of anatomical studies. The variations
      were grouped based on the presence and location of the communicating branch with
      the median nerve and the origin of branches to anterior arm muscles. Forty-three
      cadaveric studies met the inclusion criteria, providing data from 4124 plexuses.
      The overall pooled prevalence of plexuses with MCN variations was 20%. Based on
      the classification applied in our study, the pooled prevalence of variations was
      17% in region 1A, 20% in region 1B, 36% in region 2 and 49% in region 3.
      Importantly, 64.58% of variations in region 1A and 74.14% of variations in region
      1B were mixed, that is, associated with a variation in another region. The odds
      of finding another variation in the presence of a variation in region 2 or 3 were
      equal 0.37 and 0.52, respectively, demonstrating a significantly lower
      probability of finding mixed variations involving these regions, when compared
      with region 1A. Variations of the MCN are most common in the part distal to the
      exit from within or beneath the coracobrachialis muscle. Proximal variations are
      more often associated with another variation located along the nerve. These
      findings can assist health care professionals in the treatment of brachial plexus
      lesions. Clin. Anat., 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30113089
TI  - Spatial distribution of smooth muscle tissue in the male pelvic floor with
      special reference to the lateral extent of the rectourethralis muscle:
      Application to prostatectomy and proctectomy.
AB  - The anatomy of the rectourethralis muscle is essential for performing radical
      prostatectomy and proctectomy. The rectourethralis muscle is known to continue to
      the rectal wall posteriorly and to the membranous urethra anteriorly. However,
      the lateral extent of the rectourethralis muscle remains unclear. This study
      aimed to verify the hypothesis that the rectourethralis muscle laterally extends
      and directly adheres to the levator ani. Eight male cadavers were used for
      macroscopic dissection, and three male cadavers were used for immunohistological
      analysis using anti-smooth muscle and anti-skeletal muscle antibodies. The
      rectourethralis muscle laterally extended smooth muscle fibers both
      superoposteriorly and inferoanteriorly toward the levator ani. The smooth muscle
      fibers sandwiched the levator ani superoanteriorly and inferoanteriorly. A few
      smooth muscle fibers of the rectourethralis muscle inserted into the levator ani.
      This study clarified the spatial distribution of the rectourethralis muscle and
      its detailed positional relationship with the levator ani. The findings are
      valuable especially to urologists and anorectal surgeons for dissecting an
      optimal layer around the urethra and the rectum, and for avoiding rectal or
      urethral injuries during surgery. Clin. Anat., 2018. (c) 2018 Wiley Periodicals,
      Inc.

PMID- 30113090
TI  - Anatomical and functional relationships between external abdominal oblique muscle
      and posterior layer of thoracolumbar fascia.
AB  - The abdominal muscles are important for the stability of the lumbar region
      through the thoracolumbar fascia (TLF). However, there is not full agreement
      regarding the posterior transversal continuity of the external abdominal oblique
      muscle (EO) with the TLF. To clarify this point, 10 cadavers and computed
      tomography (CT) images from 27 subjects were used to evaluate the transversal
      continuity of the TLF with the abdominal muscles. The width of the fascial
      continuity of the EO with the posterior layer of TLF along the posterior border
      of the EO was also measured (40.70 +/-3.92 mm). The epimysial fascia of the EO
      was in direct continuity with the posterior layer of TLF in eight cadavers and 23
      CT images, whereas in two cadavers and four CT images, the epimysial fascia of
      the EO first fused with the fascia covering the latissimus dorsi, and then, both
      fasciae were in continuity with the posterior layer of TLF. Therefore, the
      transversal fascial continuity of the EO could explain the transmission of
      tension from the EO to the posterior layer of TLF and its importance in
      maintaining the stability of the lumbar spine through a hydraulic effect.
      Regarding fascial continuity in the trunk, and taking the EO into consideration,
      the TLF is formed by the fascia of all the abdominal muscles as the rectus
      sheath. In this manner, myofascial continuity between the TLF and the abdominal
      muscles is achieved through the aponeurosis and fascia, which ensures
      synchronization between the erector spinae and the rectus abdominis. Clin. Anat.
      31:1092-1098, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30113091
TI  - A novel marker for identifying and studying the membranes, barriers, and
      compartments surrounding peripheral nerves microscopically.
AB  - Recent anatomical discoveries indicate the importance of identifying membranes
      and compartments surrounding peripheral nerves into which local anesthetic agents
      can be injected and continuous nerve block catheters placed during regional
      anesthetic procedures. However, current markers used in anatomical studies have
      multiple drawbacks, specifically extravasation into noninjected locations, which
      can result in inadequate treatment. We studied a readily-available new marker,
      heparinized blood solution (HBS), which is easy to identify by microscopy and can
      remain in the nerve compartment into which it is deposited without distorting the
      tissue. We collected blood from 22 patients and prepared it as HBS. This was then
      injected into four fresh cadavers as in routine clinical practice for ultrasound
      guided nerve blocks to form a so-called "doughnut" by "hydro-dissecting" at 32
      sites. All samples, including nerves and neighboring tissues, were then prepared
      and examined by light microscopy. Although no deliberate intraneural injection
      was attempted, the marker was identified inside all the nerve compartments except
      the fascicles. Apart from leaking through the needle entry site in some
      instances, there was no extravasation of the HBS into neighboring nerve
      compartments in either direction. The tissues were not distorted and the
      erythrocytes did not form a thrombus. Nerve membranes and compartments could be
      clearly identified with routine staining. This technique enabled us to study the
      longitudinal and circumferential spread in all nerve compartments and to collect
      data for better interpretation of factors influencing an anesthetic nerve block
      and situations in which complications could possibly arise. HBS seemed superior
      to other markers because it did not leave the compartments into which it had been
      injected, did not distort the tissue, and was easily visible under the light
      microscope. Clin. Anat., 31:1050-1057, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30113092
TI  - Reduced differential renal function in scintigraphy predicted high-grade
      vesicoureteral reflux in children with antenatal hydronephrosiss.
AB  - AIM: A top-down approach is widely used for detecting vesicoureteral reflux (VUR)
      in children with febrile urinary tract infections. We evaluated the diagnostic
      value of renal scintigraphy in predicting VUR in children with antenatal
      hydronephrosis (AHN). METHODS: The voiding cystourethrogram (VCUG) and renal
      scintigraphy results of 125 AHN patients (76% male) admitted to the Children's
      Hospital of Helsinki University, Finland, from 2003 to 2013 were analysed. Of
      those, 94 had nonrefluxing hydronephrosis, nine had low-grade VUR and 22 had high
      grade VUR. RESULTS: Scintigraphy was performed at a median age of 1.4 (0.8-15.6)
      months. In patients with high-grade VUR, the differential renal function (DRF) of
      the worse kidney was significantly lower than in patients without VUR, with a
      median of 35% and interquartile range (IQR) of 20-45 versus 47% (IQR: 44-49), (p
      < 0.001). There was no difference between patients with low-grade VUR and
      patients without VUR (p = 0.181). DRFs below 44% showed a sensitivity of 73% and
      specificity of 79% and predicted significantly high-grade VUR (odds ratio 9.82,
      95% confidence interval 3.44-28.05, p < 0.001) in the univariate analysis.
      CONCLUSION: A DRF below 44% predicted high-grade VUR in patients with AHN and
      supported the decision to perform VCUG.

PMID- 30113093
TI  - Elaborating a coiled-coil-assembled octahedral protein cage with additional
      protein domains.
AB  - De novo design of protein nano-cages has potential applications in medicine,
      synthetic biology, and materials science. We recently developed a modular,
      symmetry-based strategy for protein assembly in which short, coiled-coil
      sequences mediate the assembly of a protein building block into a cage. The
      geometry of the cage is specified by the combination of rotational symmetries
      associated with the coiled-coil and protein building block. We have used this
      approach to design well-defined octahedral and tetrahedral cages. Here, we show
      that the cages can be further elaborated and functionalized by the addition of
      another protein domain to the free end of the coiled-coil: in this case by fusing
      maltose-binding protein to an octahedral protein cage to produce a structure with
      a designed molecular weight of ~1.8 MDa. Importantly, the addition of the maltose
      binding protein domain dramatically improved the efficiency of assembly,
      resulting in ~ 60-fold greater yield of purified protein compared to the original
      cage design. This study shows the potential of using small, coiled-coil motifs as
      off-the-shelf components to design MDa-sized protein cages to which additional
      structural or functional elements can be added in a modular manner.

PMID- 30113094
TI  - Michelangelo buonarroti's code in the frescoes of the sistine chapel - an
      allusion to gematria of the hebrew/greek alphabet and the Golden Ratio.
AB  - According to Giorgio Vasari (1511-1574), the great genius of anatomy,
      Michelangelo Buonarroti (1475-1564), in painting the frescoes on the ceiling of
      the Sistine Chapel (1508-1512), demonstrated to the world a new
      dimension/perspective of painting, especially in the sublime manner with which
      the artist represented the anatomical details of the characters that made up his
      frescoes. Since then, the Sistine Chapel has received millions of tourists
      annually, who marvel at the anatomical beauty of the characters depicted on its
      ceiling. It has also received many scholars of art and even anatomists, who have
      often tried to infer theses and explanations regarding Michelangelo's real
      intentions in elaborating this great work. However, even after five centuries,
      the Vatican's own official explanations of the true intentions of the artist
      remain quite uncertain. In an attempt to elucidate Michelangelo's possible
      intentions in the design of this memorable work, this article presents
      unpublished evidence that all the frescoes on the ceiling of the Sistine Chapel
      were organized by the artist according to a code based on the number of
      characters in each fresco, the gematria of the Hebrew/Greek alphabet, and the
      Golden Ratio. This decoding process could reveal a key factor influencing the
      artist's intentions in ordering the elements in this work. Clin. Anat. 31:948
      955, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30113095
TI  - Factors related to difficult self-expandable metallic stent placement for
      malignant colonic obstruction: A post-hoc analysis of a multicenter study across
      Japan.
AB  - BACKGROUND AND AIM: Colorectal cancer patients often present with large bowel
      obstruction. Elective placement of a self-expandable metallic stent (SEMS) can
      relieve obstruction, but can be challenging. Previous studies have compared cases
      by outcomes only, but the present study investigated successful cases only to
      identify factors related to prolonged and difficult SEMS placement in patients
      with malignant colonic obstruction. METHODS: A post-hoc analysis of a multicenter
      clinical trial conducted between March 2012 and October 2013 at 46 facilities
      across Japan (UMIN000007953) was carried out; 511 patients who required SEMS
      placement for acute colorectal obstruction or symptomatic stricture secondary to
      malignant neoplasm were enrolled. Technical success rates and procedure times
      were recorded. Clinical and interventional parameters were investigated for their
      potential effect on procedure time by univariate and multivariate analyses.
      RESULTS: Technical success rate of SEMS placement was 98%. Median procedure time
      was 30 (range, 4-170) min. In 27% of patients, procedure time exceeded 45 min,
      indicating technically difficult placement. Multivariate analyses showed
      significant associations between technically difficult placement and a ColoRectal
      Obstruction Scoring System (CROSS) score of 0 before SEMS placement (odds ratio
      [OR], 1.6; P < 0.05), tumor site in the right colon (OR, 2.5; P < 0.0001),
      stricture length >=5 cm (OR, 2.2; P < 0.001), peritoneal carcinomatosis (OR, 1.7;
      P < 0.05), and multiple SEMS placement (OR, 8.0; P < 0.01). CONCLUSION:
      Clinicians must anticipate technical challenges in cases with peritoneal
      carcinomatosis, a CROSS score of 0, or expansive strictures; such cases require
      experienced clinicians to carry out SEMS placement.

PMID- 30113096
TI  - Profile of sunless tanning product users: Results from a nationwide
      representative survey.
AB  - BACKGROUND: Sunless tanning products (STPs) are often seen as "healthy
      alternative" to sunbathing and indoor tanning. However, STP use may entail
      indirect risks such as overestimating an individual's natural skin type,
      resulting in risky (natural and artificial) tanning behavior. We aimed to explore
      STP use in combination with other health-related risk behaviors (eg, smoking),
      skin cancer risk, risk awareness of ultraviolet radiation, and preventive
      behavior. METHODS: We used data from the NCAM, a nationwide representative cross
      sectional sample (n = 3000, aged 14-45, 48.6% female) interviewed via telephone.
      Differences between STP users and nonusers regarding the abovementioned aspects
      were identified using chi2-test. RESULTS: The 1-year prevalence of STP use was
      7.5%. Tanning bed users showed a higher prevalence of STP use than past and never
      users (16.1% vs 9.6% vs 5.8%, P < 0.05). Although STP users had a higher skin
      cancer risk based on individual characteristics, they were less likely to have
      participated in a skin cancer screen. CONCLUSION: The identified parallel use of
      STPs and tanning beds can have severe health consequences, since the "fake tan"
      of STPs may lead to an overestimation of the individual's skin type, which may
      result in overdosed UV exposure. The lower risk awareness among STP users
      accompanied with their higher skin cancer risk calls for target group-specific
      prevention.

PMID- 30113097
TI  - Bisphenol A vascular toxicity: Protective effect of Vitis vinifera (grape) seed
      extract and resveratrol.
AB  - The underlying mechanism of Bisphenol A (BPA)-induced vascular toxicity and the
      protective role of grape seed extract (GSE) and resveratrol were investigated in
      vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were exposed
      to different concentrations of GSE and resveratrol. Then, BPA was added to the
      cells and cell viability and effects on the protein level of cell adhesion
      molecules were measured through MTT and western blotting. Animals were randomly
      divided into control, GSE (3 and 12 mg.kg-1 .day-1 ip), resveratrol (100 mg.kg-1
      .day-1 ip), BPA (35 mg.kg-1 .day-1 , gavage), BPA plus GSE (3, 6, and 12 mg.kg-1
      .day-1 ip), BPA plus resveratrol (25, 50, and 100 mg.kg-1 .day-1 ip), and BPA
      plus vitamin E (200 IU/kg per every other day ip). After 2 months, contractile
      and relaxant responses were evaluated on the isolated aorta. BPA increased the
      level of aorta malondialdehyde (p < 0.001) and decreased vascular responses to
      KCl (p < 0.01), phenylephrine (p < 0.001), and acetylcholine (p < 0.01). In
      HUVECs, BPA (IC50 : 220 MUM) increased protein level of vascular cell adhesion
      molecule (p < 0.05) and cleaved capase3 (p < 0.001). GSE, resveratrol, and
      vitamin E cotreatment restored toxic effects of BPA in some levels. BPA vascular
      toxicity was attributed to lipid peroxidation and endothelial dysfunction. The
      protective role of GSE and resveratrol against BPA-endothelial dysfunction could
      be attributed to their potent antioxidant properties.

PMID- 30113098
TI  - Modulating reconsolidation and extinction to regulate drug reward memory.
AB  - Drug addiction is an aberrant memory that shares the same memory processes as
      other memories. Brief exposure to drug-associated cues could result in
      reconsolidation, a hypothetical process during which original memory could be
      updated. In contrast, longer exposure times to drug-associated cues could trigger
      extinction, a process that decreases the conditioned responding. In this review,
      we discuss the pharmacological and non-pharmacological manipulations on the
      reconsolidation and extinction that could be used to interfere with drug reward
      memories. Pharmacological agents such as beta-adrenergic receptor antagonist
      propranolol can interfere with reconsolidation to disrupt drug reward memory.
      Pharmacological agents such as the NMDA receptor glycine site agonists d
      cycloserine and d-serine can facilitate extinction and then attenuate the
      expression of drug reward memory. Besides pharmacological interventions, drug
      free behavioral approaches by utilizing the reconsolidation and extinction, such
      as 'post-retrieval extinction' and 'UCS-retrieval extinction', are also effective
      to erase or inhibit the recall of drug reward memory. Taken together,
      pharmacological modulation and non-pharmacological modulation of reconsolidation
      and extinction are promising approaches to regulate drug reward memory and
      prevent relapse.

PMID- 30113099
TI  - Diatoms do radiate: evidence for a freshwater species flock.
AB  - Due to the ubiquity and high dispersal capacity of unicellular eukaryotes, their
      often extraordinary diversity found in isolated and long-lived ecosystems such as
      ancient lakes is typically attributed to multiple colonization events rather than
      to in situ speciation. However, respective evolutionary studies are very scarce
      and the often high number of species flocks in ancient lakes across multicellular
      taxa raises the question whether unicellular species, such as diatoms, may
      radiate as well. Here, we use an integrative approach that includes molecular
      data from benthic diatom species of the genus Aneumastus endemic to ancient Lake
      Ohrid, fossil data obtained from the sediment record of a recent deep-drilling
      project and biogeographical information to test if this group, indeed,
      constitutes a species flock. Molecular-clock and phylogenetic analyses indicate a
      young monophyletic group of several endemic species. Molecular, fossil and
      biogeographical data strongly suggest a rapid intralacustrine diversification,
      which was possibly triggered by the emergence of novel habitats. This finding is
      the first evidence for a species flock in diatoms and suggests that in situ
      speciation is also a relevant evolutionary process for unicellular eukaryotes in
      isolated ecosystems.

PMID- 30113100
TI  - Brain morphometry of preschool age children affected by autism spectrum disorder:
      correlation with clinical findings.
AB  - INTRODUCTION: The aim of our study was to use a combined imaging and clinical
      approach to identify possible patterns of clinical and imaging findings in a
      cohort of preschool age Autism Spectrum Disorder (ASD) patients. MATERIAL AND
      METHODS: In order to identify imaging patterns that could be related to specific
      clinical features, a selected group of ASD patients (age range 3-6 years) without
      dysmorphic features, epilepsy or other major neurological signs, malformations or
      other lesions at MRI was subjected to brain volumetric analysis using
      semiautomatic brain segmentation. An age-matched group of typically developing
      children was subjected to the same analysis. RESULTS: Our results were consistent
      with previous literature: Total Gray Matter Volume, Total Cortical Gray Matter
      Volume and amygdalar volumes were significantly greater in the ASD group than the
      control group. When we divided the study group into subgroups on the basis of
      clinical findings such as high- or low-functioning, or verbal and non-verbal, the
      only significant difference between verbal and non-verbal subjects was in
      cerebellar hemispheric size. CONCLUSIONS: Our results confirm that newer brain
      MRI techniques using semiautomatic brain segmentation can provide information
      useful for defining the differences between ASD patients and controls,
      particularly if they form part of an integrated approach between MRI and
      cognitive-behavioral and genetic data. This article is protected by copyright.
      All rights reserved.

PMID- 30113101
TI  - What do we know about the pharmacotheraputic management of insomnia in cannabis
      withdrawal: A systematic review.
AB  - BACKGROUND AND OBJECTIVES: Sleep disturbance is one of the hallmarks of cannabis
      withdrawal. Studies have indicated that treatment of this key symptom may
      facilitate abstinence. In the present paper we aim to provide a systematic review
      of the extant literature on pharmacological management of sleep disturbance
      associated with cannabis withdrawal. METHOD: We conducted a systematic literature
      search across five electronic databases including PubMed, Psycinfo, MEDLINE,
      Cochrane review and Embase. Human studies using a pharmacological treatment for
      sleep disturbances associated with cannabis withdrawal were included. Review
      articles, case-series, open trials, posters, and editorials were excluded.
      RESULTS: Seventeen publications, involving 562 participants, were included in
      this review. Major limitations involved small sample size, high dropout rate,
      methodological limitations, and heterogeneity of participants. Most of the
      studies were at high risk of bias, further downgrading the level of evidence. A
      meta-analysis was not performed due to lack of quantitative data, marked
      heterogeneity and low quality of the included studies. CONCLUSION: There is not
      sufficient evidence for any of the reviewed treatment options. Methodological
      limitations in a majority of the studies rendered their findings preliminary. Of
      the twelve investigated pharmacological agents, Gabapentin, Lofexidine,
      Mirtazapine, Quetiapine, and Zolpidem showed some primary benefits for treatment
      of sleep difficulties associated with cannabis withdrawal; however, future
      prospective studies are required to confirm such results. SCIENTIFIC
      SIGNIFICANCE: This review examines the current evidence for potential
      pharmacological options for treatment of cannabis withdrawal and associated sleep
      disturbance. It furthers our knowledge and provides groundwork for future
      research. (Am J Addict 2018;27:453-464).

PMID- 30113102
TI  - Transfer of the Dorsal Cutaneous Branch of the Ulnar Nerve for Restoration of
      Median Nerve Sensation: A Cadaveric Study.
AB  - The use of dorsal cutaneous branch of the ulnar nerve (DCBUN) transfer for median
      nerve (MN) sensory restoration has not been evaluated anatomically and
      histologically in humans. The purpose of this study was to evaluate the
      feasibility of DCBUN to MN transfer for sensory restoration with respect to nerve
      branch pattern, length, and fascicle count match.Using seven fresh frozen
      cadaveric upper limb specimens, the DCBUN and its branch patterns, lengths, and
      sizes were recorded. The MN was exposed within the carpal tunnel and dissected
      distally to identify the common digital nerves (CDN). Simulated nerve transfer
      was performed with palmar coaptation of the DCBUN branches with the CDNs.
      Histological analysis of each nerve branch was performed. The seven specimens had
      a mean of 3.57 branches (range 2-4) off the DCBUN. The longest branch innervated
      the dorsal 4th web space, on average reaching 7.6 cm distal to the wrist crease.
      Transferring the DCBUN branches palmarly did not substantially change their
      maximum distance distal to the wrist crease. The MN CDNs and DCBUN branches had
      mean cross-sectional areas of 6.37 and 1.99 mm2 , respectively, and mean fascicle
      counts of 10.4 and 4.05, respectively. The DCBUN provides 2-4 branches suitable
      for tension-free end-to-end transfer to the MN CDNs. The individual size of the
      DCBUN branch is smaller than CDN; however, combining two or more branches of the
      DCBUN would overcome the fascicle and size mismatch to reconstruct the 1st web
      space CDN for critical sensory restoration. Clin. Anat. 31:1006-1012, 2018. (c)
      2018 Wiley Periodicals, Inc.

PMID- 30113103
TI  - Porous-Carbon-Confined Formation of Monodisperse Iron Nanoparticle Yolks toward
      Versatile Nanoreactors for Metal Extraction.
AB  - All-in-one architectures in which uniform nanoscale zero-valent iron
      nanoparticles are wrapped in hollow porous carbon shells are highly desirable for
      environmental applications such as wastewater treatment and for use as catalysts,
      but their preparation remains a significant challenge. Herein, a spatially
      confined strategy for the in situ preparation of uniform Fe0 @mC
      (mC=micro/mesoporous carbon) yolk-shell nanospheres, in which the iron
      nanoparticles are encapsulated in thin, porous carbon shells, is reported. The
      elaborately designed Fe0 @mC yolk-shell nanospheres were obtained by utilizing
      silica- and phenolic-resin-coated magnetite nanoparticle core-shell structures as
      templates by means of selective etching and in situ thermal reduction. The highly
      dispersed iron nanoparticles with superior reduction capability can effectively
      remove metal pollutants (e.g., AuIII , AgI , and CuII ), the carbon shell acts as
      protective cover and prevents aggregation of iron nanoparticles, and the void
      space in the capsules serves as a reactor for reduction and catalytic reactions.

PMID- 30113105
TI  - Suicidality among gambling helpline callers: A consideration of the role of
      financial stress and conflict.
AB  - BACKGROUND AND OBJECTIVES: High rates of suicidal ideation and attempts secondary
      to gambling are well established among those with gambling disorders. The present
      study explores potential risk factors for suicidal ideation and/attempt among a
      sample of help-line callers. METHODS: Participants (N = 202) completed measures
      assessing demographics; gambling behavior; and financial, family/social,
      employment, substance use, and legal difficulties related to gambling. Bivariate
      analyses, logistic regression, and mediation analyses were used to explore
      relationship between predictors and risk of suicidal ideation and attempt.
      RESULTS: Female gender, gambling severity (including engagement in illegal
      behaviors), a history of mental health problems, financial problems, and conflict
      related to gambling were associated with current suicidality in this sample.
      Mediation analyses revealed that financial problems were associated with
      increased familial conflict, which was in turn associated with increased
      suicidality. CONCLUSIONS: Family and social conflict may be one important way in
      which financial problems confer risk for suicidality among problem gamblers.
      These results align with findings from the substance use disorder (SUD)
      literature and highlight one potential factor that may merit further assessment
      and/or intervention. SCIENTIFIC SIGNIFICANCE: Researchers and clinicians may want
      to consider the overall level of conflict a patient is experiencing when
      assessing suicide risk among individuals with gambling problems. Professionals
      may also want to consider the suitability of interventions to address conflict
      within the context of gambling treatment. (Am J Addict 2018;27:531-537).

PMID- 30113104
TI  - Fullerenols Revisited: Highly Monodispersed Photoluminescent Nanomaterials as
      Ideal Building Blocks for Supramolecular Chemistry.
AB  - Fullerenols have been known for decades; however, the photoluminescent (PL)
      properties and applications in supramolecular chemistry of these molecules have
      not been well addressed. Herein, a strategy has been developed to purify the as
      prepared fullerenols, and the photoluminescence and capabilities of these
      molecules to form supramolecular self-assemblies were systematically studied. It
      was found that fullerenols show wavelength-dependent emission with an absolute
      fluorescent quantum yield of approximately 3.5 %. The PL characteristics are
      reminiscent of carbon dots, especially those obtained by using the top-down
      method. The studied fullerenols can be used to detect Cu2+ ions with a limit of
      detection down to 3.50 MUm. In addition, the amphiphilicity of the fullerenols
      can be readily tuned by ionic complexation with cationic surfactants, such as 1
      tetradecyl-3-methylimidazoliumbromide (C14 mimB) and tetradecyltrimethylammonium
      bromide (TTAB). On increasing the concentration of the surfactant, the transition
      of aggregates was induced from highly ordered vesicles to honeycomb-structured
      crystals and finally to giant micelles. After the formation of supramolecular
      self-assemblies, enhancement of photoluminescence was observed, which can be
      ascribed to the suppression of intramolecular vibrations and motion combined with
      the loosely packed self-assembly array. This study provides a facile way to
      generate PL nanoarchitectures, which may find applications in fluorescent
      sensing, drug delivery, and optoelectronics.

PMID- 30113106
TI  - Rhodium-Catalyzed Asymmetric Allylation of Malononitriles as Masked Acyl Cyanide
      with Allenes: Efficient Access to beta,gamma-Unsaturated Carbonyls.
AB  - A rhodium-catalyzed regio- and enantioselective intermolecular allylation of
      malononitriles as masked acyl cyanides (MAC) with terminal and symmetrical
      internal allenes is reported. A RhI /Josiphos catalytic system combined with
      subsequent oxidative degradation of the primary adducts enables a straightforward
      access to alpha-branched, beta,gamma-unsaturated carbonyl compounds. The present
      protocol exhibits perfect atom economy in the allylation step and is
      characterized by a great functional group compatibility. Furthermore, the use of
      alpha-substituted malononitriles allowed for the construction of all-carbon
      quaternary centers.

PMID- 30113107
TI  - Prps1l1, a testis-specific gene, is dispensable for mouse spermatogenesis.

PMID- 30113108
TI  - Effects of different levels of modified palygorskite supplementation on the
      growth performance, immunity, oxidative status and intestinal integrity and
      barrier function of broilers.
AB  - This experiment was designed to investigate effects of different levels of
      modified palygorskite (MPal) supplementation on growth performance, immunity,
      oxidative status and intestinal integrity and barrier function of broilers. A
      total of 320 1-day-old Arbor Acres broilers were randomly assigned into 5 dietary
      treatments and fed a basal diet supplemented with 0, 0.25, 0.5, 1 and 2 g/kg
      MPal, respectively, for a 42-day feeding trial. Treatments quadratically reduced
      feed/gain ratio (F:G) during 1-21 days and linearly decreased average daily feed
      intake and F:G during 22-42 days, and linearly and quadratically decreased
      average daily feed intake and F:G during overall period (p < 0.05, 0.50 g/kg
      treatment showed the lowest F:G). MPal supplementation increased the contents of
      21-day jejunal secretory immunoglobulin A (SIgA) quadratically, and 21-day
      jejunal immunoglobulin G (IgG), immunoglobulin M (IgM) and 42-day jejunal total
      superoxide dismutase (T-SOD) activity linearly and quadratically (0.50 g/kg
      treatment showed the highest immunoglobulin concentration), whereas linearly
      reduced 21-day ileal SIgA level and 42-day jejunal malondialdehyde (MDA)
      accumulation and serum diamine oxidase activity, and quadratically decreased 21
      day ileal MDA level (p < 0.05). The 42-day jejunal SIgA, IgG and IgM
      concentrations, and T-SOD activity in jejunum at 21 days and ileum at both 21
      days and 42 days were quadratically increased with MPal administration (p < 0.05,
      0.50 g/kg treatment showed the highest T-SOD activity). The mucin 2 mRNA
      abundances in 42-day jejunum and 21-day ileum were quadratically increased with
      MPal supplementation (p < 0.05). Treatments linearly increased 42-day ileal
      zonula occludens-1, claudin-3 and jejunal claudin-3 mRNA level, whereas linearly
      and quadratically increased ileal claudin-2 mRNA level (p < 0.05). In conclusion,
      MPal supplementation exhibited beneficial effects on growth performance,
      intestinal immunity, antioxidant capacity and intestinal integrity and barrier
      function of broiler with its optimum dosage being 0.5 g/kg.

PMID- 30113109
TI  - Value of protected areas to avian persistence across 20 years of climate and land
      use change.
AB  - Establishing protected areas, where human activities and land cover changes are
      restricted, is among the most widely used strategies for biodiversity
      conservation. This practice is based on the assumption that protected areas
      buffer species from processes that drive extinction. However, protected areas can
      maintain biodiversity in the face of climate change and subsequent shifts in
      distributions have been questioned. We evaluated the degree to which protected
      areas influenced colonization and extinction patterns of 97 avian species over 20
      years in the northeastern United States. We fitted single-visit dynamic occupancy
      models to data from Breeding Bird Atlases to quantify the magnitude of the effect
      of drivers of local colonization and extinction (e.g., climate, land cover, and
      amount of protected area) in heterogeneous landscapes that varied in the amount
      of area under protection. Colonization and extinction probabilities improved as
      the amount of protected area increased, but these effects were conditional on
      landscape context and species characteristics. In this forest-dominated region,
      benefits of additional land protection were greatest when both forest cover in a
      grid square and amount of protected area in neighboring grid squares were low.
      Effects did not vary with species' migratory habit or conservation status.
      Increasing the amounts of land protection benefitted the range margins species
      but not the core range species. The greatest improvements in colonization and
      extinction rates accrued for forest birds relative to open-habitat or generalist
      species. Overall, protected areas stemmed extinction more than they promoted
      colonization. Our results indicate that land protection remains a viable
      conservation strategy despite changing habitat and climate, as protected areas
      both reduce the risk of local extinction and facilitate movement into new areas.
      Our findings suggest conservation in the face of climate change favors creation
      of new protected areas over enlarging existing ones as the optimal strategy to
      reduce extinction and provide stepping stones for the greatest number of species.

PMID- 30113110
TI  - Medical education for millennials: How anatomists are doing it right.
AB  - Millennial students born between 1980 and 1999 are currently the most prevalent
      generation in medical schools. Understanding this generation of inspiring yet
      challenging learners is key to satisfying instructional interaction. Effective
      strategies for teaching millennial learners can be summarized with 5 R's:
      ensuring a relaxed learning environment, building rapport with learners,
      highlighting the relevance and rationale of learning objectives and assessments,
      and implementing research-based educational methods. These strategies are
      exemplified by anatomists who relate (through platforms that encourage team-based
      learning in a relaxed environment), resonate (by highlighting the relevance and
      rationale of basic science learning objectives and feedback strategies), and
      innovate (by adopting cutting edge, research-proven technologies) within their
      curricula. Anatomists lead the way in effectively engaging, teaching and
      evaluating Millennial medical students in the 21st century. Broad application of
      these principles by other medical educators can further enhance Millennial
      education. Clin. Anat., 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30113111
TI  - Modulation of network-to-network connectivity via spike-timing-dependent
      noninvasive brain stimulation.
AB  - Human cognitive abilities and behavior are linked to functional coupling of many
      brain regions organized in distinct networks. Gaining insights on the role those
      networks' dynamics play in cognition and pathology requires their selective,
      reliable, and reversible manipulation. Here we document the possibility to
      manipulate the interplay between two brain networks in a controlled manner, by
      means of a Transcranial Magnetic Stimulation (TMS) protocol inducing spike timing
      dependent plasticity (STDP). Pairs of TMS pulses at specific inter-stimulus
      intervals, repeatedly delivered over two negatively correlated nodes of the
      default mode network (DMN) and the task-positive network (TPN) defined on the
      basis of individual functional magnetic resonance imaging (fMRI) data, induced a
      modulation of network-to-network connectivity, even reversing correlation from
      negative to slightly positive in 30% of cases. Results also suggest a baseline
      dependent effect, with a greater connectivity modulation observed in participants
      with weaker between-networks connectivity strength right before TMS. Finally,
      modulation of task-evoked fMRI activity patterns during a sustained attention
      task was also observed after stimulation, with a faster or slower switch between
      rest and task blocks according to the timing of TMS pulses. The present findings
      promote paired associative TMS as a promising technique for controlled
      manipulation of fMRI connectivity dynamics in humans, as well as the causal
      investigation of brain-behavior relations.

PMID- 30113113
TI  - Assisted reproductive technology is effective for but does not affect the
      prognosis of young patients with breast cancer: Experience in a single
      institution.
AB  - Assisted reproductive technology (ART) helps women preserve fertility after
      chemotherapy for cancer treatment. We examined the long-term survival of patients
      with early breast cancer who did or did not receive ART, as well as post
      treatment pregnancy and childbirth rates. Our study consisted of 44 young
      patients (<=35 years of age). Eight patients were pregnant post-treatment;
      however, none of these patients received ART intervention. ART intervention
      prevented patient omits of necessary treatment to avoid adverse events. It did
      not affect the prognosis of patients with breast cancer. Technical improvements
      are needed to increase the likelihood of pregnancy after breast cancer treatment.

PMID- 30113112
TI  - Development and evaluation of a multimodal marker of major depressive disorder.
AB  - This study aimed to identify biomarkers of major depressive disorder (MDD), by
      relating neuroimage-derived measures to binary (MDD/control), ordinal (severe
      MDD/mild MDD/control), or continuous (depression severity) outcomes. To address
      MDD heterogeneity, factors (severity of psychic depression, motivation, anxiety,
      psychosis, and sleep disturbance) were also used as outcomes. A multisite,
      multimodal imaging (diffusion MRI [dMRI] and structural MRI [sMRI]) cohort (52
      controls and 147 MDD patients) and several modeling techniques-penalized logistic
      regression, random forest, and support vector machine (SVM)-were used. An
      additional cohort (25 controls and 83 MDD patients) was used for validation. The
      optimally performing classifier (SVM) had a 26.0% misclassification rate
      (binary), 52.2 +/- 1.69% accuracy (ordinal) and r = .36 correlation coefficient
      (p < .001, continuous). Using SVM, R2 values for prediction of any MDD factors
      were <10%. Binary classification in the external data set resulted in 87.95%
      sensitivity and 32.00% specificity. Though observed classification rates are too
      low for clinical utility, four image-based features contributed to accuracy
      across all models and analyses-two dMRI-based measures (average fractional
      anisotropy in the right cuneus and left insula) and two sMRI-based measures
      (asymmetry in the volume of the pars triangularis and the cerebellum) and may
      serve as a priori regions for future analyses. The poor accuracy of
      classification and predictive results found here reflects current equivocal
      findings and sheds light on challenges of using these modalities for MDD
      biomarker identification. Further, this study suggests a paradigm (e.g., multiple
      classifier evaluation with external validation) for future studies to avoid
      nongeneralizable results.

PMID- 30113116
TI  - Copper-Catalyzed Arylation of Remote C(sp3 )-H Bonds in Carboxamides and
      Sulfonamides.
AB  - Reported herein is an unprecedented copper-catalyzed arylation of remote C(sp3 )
      H bonds. Stirring a trifluorotoluene solution of either N-fluorocarboxamides or N
      fluorosulfonamides and arylboronic acids in the presence of a catalytic amount of
      copper(II) trifluoroacetylacetonate, 2,2'-bipyridine, and sodium tert-butoxide
      afforded the gamma- and delta-C(sp3 )-H arylated carboxamides and sulfonamides,
      respectively, in good to high yields. Mechanistic studies indicate that the
      reaction might proceed through an amidyl radical generation, 1,5-hydrogen atom
      transfer (HAT), and copper-catalyzed cross-coupling of the resulting carbon
      radical with arylboronic acids.

PMID- 30113115
TI  - Sofosbuvir with NS5A inhibitors in hepatitis C virus infection with severe renal
      insufficiency.
AB  - Treatment of Hepatitis C virus (HCV) in patients with severe renal insufficiency
      is cumbersome as sofosbuvir is mainly excreted by the kidneys. There is paucity
      of data on the use of sofosbuvir and NS5A inhibitors in these patients. We hereby
      report our experience of treating chronic hepatitis C in patients with severe
      renal insufficiency with full dose sofosbuvir and NS5A inhibitors. Forty-seven
      patients with severe renal insufficiency (on dialysis n = 39, predialysis n = 8)
      with HCV infection were treated between December 2015-August 2017 with full dose
      sofosbuvir with ledipasvir or daclatasvir for 12/24 weeks depending on the
      genotype and the presence or absence of cirrhosis. The distribution of HCV
      genotype was genotype 1 in 32 (68.1%), genotype 3 in 13 (27.7%) and 4 in 2 (4.3%)
      patients. Among 12 (25.5%) patients with cirrhosis, 7 (14.9%) were decompensated
      with ascites. All patients had end of treatment response, and sustained viral
      response at 12 weeks was achieved in 45 (95.7%) patients. There was significant
      improvement in liver stiffness at 3 months after treatment (8.8 (3.8-42) to 7.1
      (3.3-24.1) kPa; (P = 0.047)). There was no change in haemoglobin and eGFR with
      treatment in predialysis group (haemoglobin- 10.2 +/- 1.5 g/dL vs 9.6 +/- 1.3
      g/dL, P = 0.44; eGFR- 19.8 +/- 9.4 mL/min vs 17.9 +/- 8.5 mL/min, P = 0.67).
      Therapy was very well accepted. Full dose sofosbuvir with NS5A inhibitors is a
      well tolerated and effective therapy for HCV infection in severe renal
      insufficiency.

PMID- 30113117
TI  - Computed microtomography study of untreated, shaped and filled mesiobuccal canals
      of maxillary first molars.
AB  - This study assessed the effectiveness of modern endodontic shaping and filling
      procedures on mesiobuccal roots of maxillary molars with two canals. The canals
      of 20 mesiobuccal roots were treated with Mtwo rotary files, passive ultrasonic
      irrigation and Guttafusion obturators. X-ray computed microtomography analysis
      was carried out prior to treatment, after canal shaping and after canal filling
      to determine the alterations of the canal volume before and after the
      instrumentation, the volume of the hard tissue debris, and percentage of the
      volume occupied by filling materials. The shaping instruments and filling
      materials reached only partially the endodontic space of the second mesiobuccal
      canal and the accessory endodontic structures. Canal irregularities,
      ramifications, and interconnections were accumulation sites of hard tissue
      debris. This study demonstrated that rotary files, passive ultrasonic irrigation
      and carrier-based filling systems could be partially effective for the treatment
      of the mesiobuccal canals and their accessory endodontic structures.

PMID- 30113118
TI  - Accounting for the shared environment in cognitive abilities and academic
      achievement with measured socioecological contexts.
AB  - Behavioral and molecular genetic research has established that child cognitive
      ability and academic performance are substantially heritable, but genetic
      variation does not account for all of the stratification of cognitive and
      academic outcomes across families. Which specific contexts and experiences
      contribute to these shared environmental influences on cognitive ability and
      academic achievement? Using an ethnically and socioeconomically diverse sample of
      N = 1728 twins ages 7-20 from the Texas Twin Project, we identified specific
      measured family, school, and neighborhood socioecological contexts that
      statistically accounted for latent shared environmental variance in cognitive
      abilities and academic skills. Composite measures of parent socioeconomic status
      (SES), school demographic composition, and neighborhood SES accounted for
      moderate proportions of variation in IQ and achievement. Total variance explained
      by the multilevel contexts ranged from 15% to 22%. The influence of family SES on
      IQ and achievement overlapped substantially with the influence of school and
      neighborhood predictors. Together with race, the measured socioecological
      contexts explained 100% of shared environmental influences on IQ and
      approximately 79% of shared environmental influences on both verbal comprehension
      and reading ability. In contrast, nontrivial proportions of shared environmental
      variation in math performance were left unexplained. We highlight the potential
      utility of constructing "polyenvironmental risk scores" in an effort to better
      predict developmental outcomes and to quantify children's and adolescents'
      interrelated networks of experiences. A video abstract of this article can be
      viewed at: https://youtu.be/77E_DctFsr0.

PMID- 30113114
TI  - Sustained versus instantaneous connectivity differentiates cognitive functions of
      processing speed and episodic memory.
AB  - Synchrony of brain activity over time describes the functional connectivity
      between brain regions but does not address the temporal component of this
      relationship. We propose a complementary method of analysis by introducing the
      width of cross-correlation curves between functional MRI (fMRI) time series as a
      metric of the relative duration of synchronous activity between brain regions, or
      "sustained connectivity". Using resting-state fMRI, cognitive, and demographics
      data from 1,003 subjects included in the Human Connectome Project, we find that
      sustained connectivity is a reproducible trait in individuals, heritable, more
      transient in females, and shows changes with age in early adulthood. Sustained
      connectivity in sensory brain regions is specifically associated with differences
      in processing speed across subjects, particularly in men. In contrast,
      traditional functional connectivity was correlated with a measure of episodic
      memory, but not with processing speed. Individual differences in hemodynamic
      response function (HRF) are closely approximated by sustained connectivity and
      width of the HRF is also correlated with processing speed across individuals,
      suggesting that variability in hemodynamic response may be influenced by
      transient versus sustained neural activity rather than simply differences in
      vascularity and signal transduction. Sustained connectivity may provide new
      opportunities to study brain dynamics in clinical populations.

PMID- 30113119
TI  - Genomics-Driven Discovery of a Symbiont-Specific Cyclopeptide from Bacteria
      Residing in the Rice Seedling Blight Fungus.
AB  - The rice seedling blight fungus Rhizopus microsporus harbors endosymbiotic
      bacteria (Burkholderia rhizoxinica) that produce the virulence factor rhizoxin
      and control host development. Genome mining indicated a massive inventory of
      cryptic nonribosomal peptide synthetase (NRPS) genes, which have not yet been
      linked to any natural products. The discovery and full characterization of a
      novel cyclopeptide from endofungal bacteria is reported. In silico analysis of an
      orphan, symbiont-specific NRPS predicted the structure of a nonribosomal peptide,
      which was targeted by LC-MS/MS profiling of wild-type and engineered null
      mutants. NMR spectroscopy and chemical derivatization elucidated the structure of
      the bacterial cyclopeptide. Phylogenetic analyses revealed the relationship of
      starter C domains for rare N-acetyl-capped peptides. Heptarhizin is produced
      under symbiotic conditions in geographically constrained strains from the Pacific
      clade; this indicates a potential ecological role of the peptide.

PMID- 30113121
TI  - Self-Assembly of an Anion-Binding Cryptand for the Selective Encapsulation,
      Sequestration, and Precipitation of Phosphate from Aqueous Systems.
AB  - The self-assembled trimetallic species [L2 Cu3 ]6+ contains a cavity that acts as
      a host to many different anions. By using X-ray crystallography, ESI-MS, and
      UV/Vis spectroscopy we show that these anions are encapsulated both in the solid
      state and aqueous systems. Upon encapsulation, the anions Br- , I- , CO32- ,
      SiF62- , IO63- , VO43- , WO42- , CrO42- , SO42- , AsO43- , and PO43- are all
      precipitated from aqueous solution and can be removed by filtration. Furthermore,
      the cavity can be tuned to be selective to either phosphate or sulfate anions by
      variation of the pH. Phosphate anions can be removed from water, even in the
      presence of other common anions, reducing the concentration from 1000 to <0.1 ppm
      and recovering approximately 99 % of the phosphate anions.

PMID- 30113120
TI  - Heart failure with preserved ejection fraction in Asia.
AB  - BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a global
      public health problem. Unfortunately, little is known about HFpEF across Asia.
      METHODS AND RESULTS: We prospectively studied clinical characteristics,
      echocardiographic parameters and outcomes in 1204 patients with HFpEF (left
      ventricular ejection fraction >=50%) from 11 Asian regions, grouped as Northeast
      Asia (Hong Kong, Taiwan, China, Japan, Korea, n = 543), South Asia (India, n =
      252), and Southeast Asia (Malaysia, Thailand, Singapore, Indonesia, Philippines,
      n = 409). Mean age was 68 +/-12 years (37% were < 65 years) and 50% were women.
      Seventy per cent of patients had >=2 co-morbidities, most commonly hypertension
      (71%), followed by anaemia (57%), chronic kidney disease (50%), diabetes (45%),
      coronary artery disease (29%), atrial fibrillation (29%) and obesity (26%).
      Southeast Asian patients had the highest prevalence of all co-morbidities except
      atrial fibrillation, South Asians had the lowest prevalence of all co-morbidities
      except anaemia and obesity, and Northeast Asians had more atrial fibrillation.
      Left ventricular hypertrophy and concentric remodelling were most prominent among
      Southeast and South Asians, respectively (P < 0.001). Overall, 12.1% of patients
      died or were hospitalized for heart failure within 1 year. Southeast Asians were
      at higher risk for adverse outcomes, independent of co-morbidity burden and
      cardiac geometry. CONCLUSION: These first prospective multinational data from
      Asia show that HFpEF affects relatively young patients with a high burden of co
      morbidities. Regional differences in types of co-morbidities, cardiac remodelling
      and outcomes of HFpEF across Asia have important implications for public health
      measures and global HFpEF trial design.

PMID- 30113122
TI  - Effect of whey protein supplementation after resistance exercise on the muscle
      mass and physical function of healthy older women: A randomized controlled trial.
AB  - AIM: To evaluate the effectiveness of a 24-week program of nutritional
      supplementation using whey protein, ingested after resistance exercise, in
      increasing muscle mass and physical function among community-dwelling healthy
      older Japanese women. METHODS: We carried out a randomized controlled trial, with
      81 healthy women, aged 65-80 years, allocated to three groups of 27 participants
      each: the exercise and protein supplementation group, the exercise only group,
      and the protein supplementation only group. A 24-week program of resistance
      exercise, carried out twice per week, was combined with whey protein
      supplementation, containing 22.3 g of protein. The total protein intake for
      participants in all three experimental groups was adjusted to a level of at least
      1.2 g/kg bodyweight/day, and more during the intervention period. Between-group
      differences in the pre- to post-intervention change in skeletal muscle mass and
      physical function were evaluated using an analysis of variance. RESULTS: The pre-
      to post-intervention increase in the skeletal muscle mass index was significantly
      higher for the exercise only group than for the protein supplementation only
      group (P =0.008), and significantly higher for the exercise and protein
      supplementation group than for either the exercise only (P =0.007) or protein
      supplementation only (P <0.001) groups. Similarly, the increase in grip strength
      and gait speed was significantly greater for the exercise and protein
      supplementation group than for the protein supplementation only group (grip
      strength P =0.014, gait speed P =0.026). CONCLUSIONS: Whey protein
      supplementation, ingested after resistance exercise, could be effective for the
      prevention of sarcopenia among healthy community-dwelling older Japanese women.
      Geriatr Gerontol Int 2018; 18: 1398-1404.

PMID- 30113123
TI  - Nickel-Catalyzed Amide Bond Formation from Methyl Esters.
AB  - Despite being one of the most important and frequently run chemical reactions,
      the synthesis of amide bonds is accomplished primarily by wasteful methods that
      proceed by stoichiometric activation of one of the starting materials. We report
      a nickel-catalyzed procedure that can enable diverse amides to be synthesized
      from abundant methyl ester starting materials, producing only volatile alcohol as
      a stoichiometric waste product. In contrast to acid- and base-mediated
      amidations, the reaction is proposed to proceed by a neutral cross coupling-type
      mechanism, opening up new opportunities for direct, efficient, chemoselective
      synthesis.

PMID- 30113124
TI  - Structural and functional cerebral bases of diminished inhibitory control during
      healthy aging.
AB  - Inhibitory control or the ability to refrain from incorrect responses is a
      critical executive function known to diminish during aging. Imaging studies have
      elucidated cerebral changes that may underlie the age-related deficits. However,
      it remains unclear whether the structural and functional changes occur in the
      same brain regions and whether reduced gray matter volumes (GMV) mediate
      decreased activation during inhibition. Here, in a sample of 149 participants, we
      addressed the issues using structural and functional magnetic resonance imaging.
      Individual's response inhibition was evaluated by the stop signal reaction time
      (SSRT) in a stop signal task. The results showed that age was associated with
      prolonged SSRT across participants. Many cortical and subcortical regions
      demonstrated age-related reduction in GMV and activation to response inhibition.
      Additionally, age-related diminution in inhibitory control, as indexed by the
      SSRT, was associated with both shared and distinct morphometric and functional
      changes. Voxel-based morphometry demonstrated age-related reduction in GMV in the
      right dorsolateral prefrontal cortex and caudate head as well as bilateral
      insula, in association with prolonged SSRT. In a contrast of stop success versus
      go success trials, age was associated with lower activation in the medial and
      inferior frontal cortex and inferior parietal cortex. Further, reduction in GMV
      mediated age-related differences in activations only of the medial prefrontal
      cortex, providing limited evidence for structure function association. Thus, the
      decline in inhibitory control, as evidenced in the stop signal task, manifest
      with both shared and distinct structural and functional processes during aging.

PMID- 30113125
TI  - Clinical spectrum of vitreoretinal lymphoma and its association with MyD88 L265P
      mutation.

PMID- 30113126
TI  - Rehabilitation of the edentulous mandible with implant-supported overdentures on
      telescopic abutments and immediate loading. A controlled prospective clinical
      study.
AB  - : The rehabilitation of the edentulous mandible with implant-supported
      overdentures is an established clinical procedure but immediate loading of
      implants supporting mandibular overdentures has not been equally documented. AIM:
      The aim of this prospective clinical study was to evaluate the rehabilitation of
      the edentulous mandible with immediate loading and implant-supported
      overdentures. MATERIALS AND METHODS: 10 patients were restored with immediate
      loading of the implants and 5 with delayed loading. The treatment planning
      included placement of four implants in the interforaminal area of the mandible.
      Prefabricated titanium abutments with 4 degrees of conical inclination were fixed
      on the implants and the telescoping conical caps were connected to the base of
      the mandibular denture. Bone loss was assessed by comparison of panoramic x-rays
      at baseline 3, 6, and 36 months by visual observation from clinicians. RESULTS: A
      total of 60 implants were restored, 40 with immediate and 20 with delayed
      loading. The follow-up period ranged from 4 to 10 years with 72 months mean
      observation time. Prosthetic complications appeared with low frequency and no
      implant loss occurred during the follow-up period. No statistical significance
      was observed in the bone loss in the cervical area of the immediate and late
      loaded implants. CLINICAL SIGNIFICANCE: The rehabilitation of the edentulous
      mandible with implant-supported overdentures and telescopic copings is a viable
      clinical solutions with multiple clinical advantages both for the clinician and
      the patient. . Immediate loading can be applied in cases where increased initial
      stability can be achieved. More extended long-term clinical studies with
      increased number of patients and implants are needed, however, to verify the
      efficacy of the treatment method.

PMID- 30113127
TI  - Pharmacotherapy vs surgery as initial therapy for patients with moderate-to
      severe benign prostate hyperplasia: a cost-effectiveness analysis.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of using a surgery, such as
      transurethral resection of the prostate (TURP) or photoselective vaporisation of
      the prostate using greenlight laser (GL-PVP), as initial treatment for men with
      moderate-to-severe benign prostate hyperplasia (BPH) compared to the standard
      practice of using pharmacotherapy as initial treatment followed by surgery if
      symptoms do not resolve. PATIENTS AND METHODS: We compared a combination of eight
      strategies involving upfront pharmacotherapy (i.e., alpha-blocker, 5alpha
      reductase inhibitor, or combination) followed by surgery (e.g. TURP or GL-PVP)
      upon failure vs TURP or GL-PVP as initial treatment, for a target population of
      men with moderate-to-severe BPH symptoms, with a mean age of 65 years and no
      contraindications for treatment. A microsimulation decision-analytic model was
      developed to project the costs and quality-adjusted life years (QALYs) of the
      target population over the lifetime. The model was populated and validated using
      published literature. Incremental cost-effectiveness ratios (ICERs) were
      determined. Cost-effectiveness was evaluated using a public payer perspective, a
      lifetime horizon, a discount rate of 1.5%, and a cost-effectiveness threshold of
      $50 000 (Canadian dollars)/QALY. Sensitivity and probabilistic analyses were
      performed. RESULTS: All options involving an upfront pharmacotherapy followed by
      TURP for those who fail were economically unattractive compared to strategies
      involving a GL-PVP for those who fail, and compared to using either BPH surgery
      as initial treatment. Overall, upfront TURP was the most costly and effective
      option, followed closely by upfront GL-PVP. On average, upfront TURP costs $1015
      more and resulted in a small gain of 0.03 QALYs compared to upfront GL-PVP,
      translating to an incremental cost per QALY gained of $29 066. Results were
      robust to probabilistic analysis. CONCLUSIONS: Surgery is cost-effective as
      initial therapy for BPH. However, the health and economic evidence should be
      considered concurrently with patient preferences and risk attitudes towards
      different therapy options.

PMID- 30113128
TI  - Primary cryotherapy for localised or locally advanced prostate cancer.
AB  - Cryotherapy is a minimally invasive treatment option of prostate cancer that
      involves freezing of the whole prostate (whole gland therapy) or only the cancer
      (focal therapy), but it is unclear how effective this is in comparison to
      standard treatments such as radical prostatectomy and radiotherapy [1,2]. We
      updated a previously published Cochrane Review to assess the effects of
      cryotherapy (whole gland or focal) compared with other interventions for primary
      treatment of clinically localized (cT1-T2) or locally-advanced (cT3) non
      metastatic prostate cancer by performing a comprehensive search of multiple
      databases (CENTRAL, MEDLINE, EMBASE), clinical trial registries and a grey
      literature repository up to 6 March 2018 [3]. We also searched the reference
      lists of other relevant publications and conference proceedings. This article is
      protected by copyright. All rights reserved.

PMID- 30113129
TI  - Assessment of marginal adaptation and fracture resistance of endocrown
      restorations utilizing different machinable blocks subjected to thermomechanical
      aging.
AB  - OBJECTIVE: This in vitro study was conducted to assess the marginal adaptation
      and fracture resistance of computer aided design/computer aided manufacturer (CAD
      CAM) fabricated endocrowns restoring endodontically treated molars using
      different machinable blocks with thermomechanical loading protocols. MATERIALS
      AND METHODS: Devitalized mandibular molars were prepared in a standardized way
      and divided into 4 groups (n = 10) to receive CAD/CAM fabricated endocrowns using
      four materials (Lithium disilicate ceramics, polymer infiltrated ceramics,
      zirconia-reinforced lithium silicate ceramics and resin nanoceramics. Marginal
      gaps (um) were measured using stereomicroscope before cementation and after
      cementation. After thermomechanical aging, marginal gap measurements were
      repeated, and then fracture resistance test was performed. Two-way analysis of
      variance (ANOVA) and Tukey HSD multiple comparisons were used to assess the
      effect of material on the marginal gap before, after cementation, and after
      thermomechanical aging. One Way ANOVA was used to assess the effect of material
      on the fracture resistance. RESULTS: The difference between marginal gaps values
      of the tested materials was statistically insignificant but with significant
      increase after cementation and after thermomechanical aging. Cerasmart endocrowns
      showed the highest mean fracture load value (1508.5 +/- 421.7N) with
      statistically significant difference than Vita Enamic endocrowns and Celtra Duo.
      CONCLUSION: The tested materials showed marginal vertical gap readings within the
      limits of clinically acceptable standards. Resin nanoceramics and lithium
      disilicate showed the highest values of fracture resistance followed by polymer
      infiltrated ceramics favoring their use for endocrown restorations. CLINICAL
      SIGNIFICANCE: The mechanical behavior of ceramic materials varies with the
      variation of their structure and mechanical properties. Accordingly, further
      investigation is always needed to explore the biomechanical behavior of recent
      materials when used as endocrowns before clinical trials.

PMID- 30113130
TI  - In Vitro Gut Metabolism of [U-13 C]-Quinic Acid, The Other Hydrolysis Product of
      Chlorogenic Acid.
AB  - SCOPE: Quinic acid in its free form is broadly abundant in plants, and can
      accumulate in copious amounts in coffee, tea, and certain fruits. However, it has
      been mostly studied as chlorogenic acid, an ester of caffeic and quinic acids.
      When chlorogenic acid reaches the colon, it is hydrolyzed by microbial esterases
      releasing caffeic and quinic acids. While biotransformation of chlorogenic and
      caffeic acids have been elucidated by in vitro and in vivo studies, the gut
      metabolism of quinic acid has been so far overlooked. METHODS AND RESULTS: [U-13
      C]-Quinic acid is submitted to a colonic model using human fecal microbiota for
      assessing its metabolic fate. The metabolite profiles formed along microbial
      biotransformation are monitored by a combined metabolomics approach, using both
      2D GC- and ultra-HPLC-MS. Six metabolic intermediates are identified by
      incorporation of isotopic label. CONCLUSION: Two parallel degradation pathways
      could be proposed: (1) an oxidative route, leading to aromatization and
      accumulation of protocatechuic acid, and a (2) reductive route, including
      dehydroxylation to cyclohexane carboxylic acid. Elucidating the biotransformation
      of food bioactives by the gut microbiota is of relevance for understanding
      nutrition, interindividual variability and potential effects on human metabolism.

PMID- 30113131
TI  - Macroeconomic impact of foot-and-mouth disease vaccination strategies for an
      outbreak in the Midwestern United States: A computable general equilibrium.
AB  - The impacts of alternative responses to a hypothetical foot-and-mouth disease
      (FMD) outbreak occurring in the Midwestern United States are estimated using the
      Regional Economic Modelling Incorporated Policy Insight + (REMI) computable
      general equilibrium model, with particular attention paid to the employment
      impact estimates. The impact on employment and GDP is estimated using forecasts
      of a 10-year period with disease outbreak duration up to 2 years. Fifteen
      different vaccination protocols are compared to a disease control protocol that
      relies on animal depopulation with no vaccination. Results show that over the 10
      year study period, the strictly depopulation strategy that made no use of
      vaccination results in approximately 677,000 jobs lost with $47 billion GDP loss.
      Based on the analysis conducted, losses can be reduced through protocols that
      utilize vaccination strategies. Through a vaccinate-to-live strategy with the
      highest vaccination capacity and largest vaccination zone, savings can be as many
      as 509,000 jobs in comparison to the strategy that relies strictly on slaughter
      with no use of vaccination. By including detailed job losses by occupation, this
      study highlights the downstream employment effects and shows that job losses
      resulting from an FMD outbreak can go far beyond the farm sector impacts that
      have been reported in earlier studies. Understanding the impacts on employment by
      sector provides more actionable information than producer and consumer surplus
      estimates frequently reported in economic impact studies.

PMID- 30113132
TI  - Aortic dissection detection risk score has high sensitivity with moderate inter
      rater reliability.
AB  - OBJECTIVE: To retrospectively assess the accuracy and inter-rater reliability of
      the aortic dissection detection risk score (ADD-RS). METHODS: Single-centre,
      observational, diagnostic accuracy study undertaken in a university-affiliated,
      tertiary hospital ED. RESULTS: Two hundred patients were enrolled. Five patients
      were diagnosed with acute aortic dissection and had an elevated ADD-RS >0. The
      ADD-RS was 100% sensitive with a negative and positive predictive values of 100%
      (if ADD-RS >=1). Inter-rater reliability was moderate (Kappa = 0.55). CONCLUSION:
      The ADD-RS was highly sensitive in our cohort. Further work to evaluate the score
      prospectively and in combination with a D-Dimer is required.

PMID- 30113133
TI  - The effects of work-family interface on domain-specific satisfaction and well
      being across nations: The moderating effects of individualistic culture and
      economic development.
AB  - Work-family conflict (WFC) and work-family enrichment (WFE) have been shown to be
      important predictors of employees' domain-specific satisfaction and well-being.
      In this meta-analysis, we consider how the effects of WFC/WFE on various outcomes
      differ across different national cultures and economic settings. We hypothesized
      that WFC would have stronger effects on employees' domain-specific satisfaction
      and well-being in high individualistic nations and economies with higher levels
      of economic development, whereas WFE would have stronger effects on employees'
      domain-specific satisfaction and well-being in low individualistic nations and
      economies with lower levels of economic development. Results generally supported
      these hypotheses, suggesting that employees in more individualistic and more
      developed countries are more sensitive to how work interferes with family life,
      whereas employees in less individualistic and less developed countries are more
      sensitive to how work provides material, social, and cognitive resources that
      help in the fulfillment of family roles. Further research is needed exploring
      more detailed explanations for these differences and their implications for
      spillover theory and work-family practices in organizations.

PMID- 30113134
TI  - Heritability estimates of spatial working memory and set-shifting in a healthy
      Chinese twin sample: A preliminary study.
AB  - Impairments in spatial working memory (SWM) and set-shifting abilities have both
      been consistently observed in individuals with schizophrenia and are considered
      to be potential endophenotypes of this illness. However, an endophenotype needs
      to fulfill a set of stringent criteria, including heritability. This study
      examined the heritability of these two functions in a healthy Chinese twin
      sample. Forty-five pairs of monozygotic (MZ) twins and 35 pairs of dizygotic (DZ)
      twins completed the SWM task and the Intra-Extra Dimensional Set-Shifting (IED)
      task of the Cambridge Neuropsychological Test Automated Battery (CANTAB). We
      found a moderate heritability for SWM, of which the familial/genetic factors
      accounted for 33% of the total variance. However, we failed to find any
      significant heritability for set-shifting ability, of which the specific
      environmental factor explained most of the variance (85%). The preliminary
      findings from this small healthy Chinese twin sample suggest that SWM is
      heritable, whereas the set-shifting ability may reflect "extra-genetic"
      influences.

PMID- 30113135
TI  - An Electrospun Core-Shell Nanofiber Web as a High-Performance Cathode for Iron
      Disulfide-Based Rechargeable Lithium Batteries.
AB  - FeS2 /C core-shell nanofiber webs were synthesized for the first time by a unique
      synthesis strategy that couples electrospinning and carbon coating of the
      nanofibers with sucrose. The design of the one-dimensional core-shell morphology
      was found to be greatly beneficial for accommodating the volume changes
      encountered during cycling, to induce shorter lithium ion diffusion pathways in
      the electrode, and to prevent sulfur dissolution during cycling. A high discharge
      capacity of 545 mAh g-1 was retained after 500 cycles at 1 C, exhibiting
      excellent stable cycling performance with 98.8 % capacity retention at the last
      cycle. High specific capacities of 854 mAh g-1 , 518 mAh g-1 , and 208 mAh g-1
      were obtained at 0.1 C, 1 C, and 10 C rates, respectively, demonstrating the
      exceptional rate capability of this nanofiber web cathode.

PMID- 30113137
TI  - Metaphyseal burst sign: A secondary sign on MRI of subchondral insufficiency
      fracture of the knee.
AB  - INTRODUCTION: To describe a novel secondary sign of subchondral insufficiency
      fracture of the knee, metaphyseal burst sign (soft tissue oedema in the meta
      epiphyseal region of the affected condyle). METHODS: An electronic database
      research of 7926 knee MRI examinations was performed. Forty-eight scans were
      included in the study. The diagnosis of subchondral insufficiency fracture (SIF)
      was confirmed in a consensus review by one fellowship trained musculoskeletal
      (MSK) radiologist and one radiology fellow. The presence of metaphyseal burst
      sign was evaluated in the cohort. RESULTS: Forty-one patients were included in
      the study (21 males, 20 females). The mean age was 61.5 years (range 41-80
      years). The anatomical location was medial femoral condyle (n = 28), the lateral
      femoral condyle (n = 5) and medial tibial condyle (n = 8). The metaphyseal burst
      sign was present in 45 of the 48 scans reviewed. The average craniocaudal length
      of the soft tissue oedema defined as metaphyseal burst sign was 7 cm (range 10.5
      to 4.5). CONCLUSION: The metaphyseal burst sign is an early, indirect sign of
      SIF.

PMID- 30113136
TI  - Clinical procedures, designs, and survival rates of all-ceramic resin-bonded
      fixed dental prostheses in the anterior region: A systematic review.
AB  - OBJECTIVES: The aim of this study is to systematically review all the clinical
      articles about all-ceramic resin-bonded fixed dental prosthesis (RBFDP) in the
      anterior region and assess their designs, clinical procedures, and survival
      rates. A systematic review was conducted after searching electronic databases
      PubMed/Medline and EBSCOhost Research Databases for articles published in English
      between 1987 and July 2017. MATERIALS AND METHODS: The inclusion criteria were
      selected as all clinical studies, original design clinical reports, and clinical
      reports (follow-up time more than 1 year) as all clinical information in the
      literature are desired to be included in the present review. RESULTS: The initial
      electronic search generated 472 articles from PubMed/Medline and 464 articles
      from EBSCOhost Research Databases. After selection of the articles as per the
      inclusion criteria, a final sample of 29 original studies is decided as: 1
      randomized controlled clinical trial, 4 clinical controlled trials, 4 prospective
      cohort studies, 2 retrospective cohort studies, 6 original design clinical
      reports, and 12 clinical reports. After evaluation of the selected articles, it
      is likely that cantilever design all-ceramic RBFDPs are more successful than two
      retainer design in the anterior region; however, there is limited evidence for
      this result in the literature. CONCLUSION: Well-designed randomized controlled
      clinical trials with large sample size are still needed to achieve more accurate
      results about the clinical success rate of different RBFDPs designs in the
      anterior region. CLINICAL SIGNIFICANCE: Indications, designs, abutment teeth
      preparation, provisionalization, try-in, surface treatment options, and
      cementation of the all-ceramic resin-bonded fixed dental prostheses are described
      in this article. Clinical survival rates are also given in detail, so that
      clinicians can easily compare the current studies and give their own decision
      about all-ceramic resin-bonded fixed dental prostheses in the anterior region.

PMID- 30113138
TI  - Implementation of multiparametric magnetic resonance imaging technology for
      evaluation of patients with suspicion for prostate cancer in the clinical
      practice setting.
AB  - OBJECTIVES: To investigate the impact of implementing magnetic resonance imaging
      (MRI) and ultrasonography fusion technology on biopsy and prostate cancer (PCa)
      detection rates in men presenting with clinical suspicion for PCa in the clinical
      practice setting. PATIENTS AND METHODS: We performed a review of 1 808
      consecutive men referred for elevated prostate-specific antigen (PSA) level
      between 2011 and 2014. The study population was divided into two groups based on
      whether MRI was used as a risk stratification tool. Univariable and multivariable
      analyses of biopsy rates and overall and clinically significant PCa detection
      rates between groups were performed. RESULTS: The MRI and PSA-only groups
      consisted of 1 020 and 788 patients, respectively. A total of 465 patients
      (45.6%) in the MRI group and 442 (56.1%) in the PSA-only group underwent biopsy,
      corresponding to an 18.7% decrease in the proportion of patients receiving biopsy
      in the MRI group (P < 0.001). Overall PCa (56.8% vs 40.7%; P < 0.001) and
      clinically significant PCa detection (47.3% vs 31.0%; P < 0.001) was
      significantly higher in the MRI vs the PSA-only group. In logistic regression
      analyses, the odds of overall PCa detection (odds ratio [OR] 1.74, 95% confidence
      interval [CI] 1.29-2.35; P < 0.001) and clinically significant PCa detection (OR
      2.04, 95% CI 1.48-2.80; P < 0.001) were higher in the MRI than in the PSA-only
      group after adjusting for clinically relevant PCa variables. CONCLUSION: Among
      men presenting with clinical suspicion for PCa, addition of MRI increases
      detection of clinically significant cancers while reducing prostate biopsy rates
      when implemented in a clinical practice setting.

PMID- 30113139
TI  - Discovery of a Potent, Long-Acting, and CNS-Active Inhibitor (BIA 10-2474) of
      Fatty Acid Amide Hydrolase.
AB  - Fatty acid amide hydrolase (FAAH) can be targeted for the treatment of pain
      associated with various medical conditions. Herein we report the design and
      synthesis of a novel series of heterocyclic-N-carboxamide FAAH inhibitors that
      have a good alignment of potency, metabolic stability and selectivity for FAAH
      over monoacylglycerol lipase (MAGL) and carboxylesterases (CEs). Lead
      optimization efforts carried out with benzotriazolyl- and imidazolyl-N
      carboxamide series led to the discovery of clinical candidate 8 l (3-(1
      (cyclohexyl(methyl)carbamoyl)-1H-imidazol-4-yl)pyridine 1-oxide; BIA 10-2474) as
      a potent and long-acting inhibitor of FAAH. However, during a Phase I clinical
      trial with compound 8 l, unexpected and unpredictable serious neurological
      adverse events occurred, affecting five healthy volunteers, including the death
      of one subject.

PMID- 30113140
TI  - Serum soluble receptor for advanced glycation end-products during acute
      bronchiolitis in infant: Prospective study in 93 cases.
AB  - INTRODUCTION: Acute bronchiolitis is a major cause of acute respiratory distress
      in infants. The soluble receptor for advanced glycation end-products (sRAGE) is a
      biomarker of pulmonary damage processes, with a diagnostic and a prognostic value
      in acute respiratory distress syndrome (ARDS). The RAGE pathway is also
      implicated in the pathogenesis of other respiratory diseases like asthma, but the
      value of sRAGE levels in acute bronchiolitis remains under-investigated. MATERIAL
      AND METHODS: A prospective, observational, and analytical study was conducted at
      Clermont-Ferrand University Hospital. The main objective was to evaluate the
      correlation between serum sRAGE and clinical severity of bronchiolitis in
      hospitalized infants aged <1 year. We analyzed correlations between serum sRAGE
      and Wainwright score, short-term morbidity attributable to bronchiolitis, causal
      viruses and risk for recurrent wheezing at 1 year. RESULTS: The study included 93
      infants. sRAGE levels were significantly lower in acute bronchiolitis patients
      (mean 1101 pg/mL) than in controls (2203 pg/mL, P < 0.001) but did not correlate
      with clinical severity. No correlation was found between serum sRAGE and severity
      score, respiratory viruses, and recurrent wheezing at 1 year. Serum sRAGE levels
      were negatively correlated with age (r = -0.45, P < 0.001). CONCLUSION: Serum
      sRAGE levels are decreased in acute bronchiolitis but not correlated with disease
      severity. sRAGE levels should be age-adjusted in infants. Serum sRAGE levels
      measured in the setting of acute bronchiolitis were not predictive of recurrent
      wheezing.

PMID- 30113141
TI  - Anogenital distance and reproductive outcomes in 9- to 11-year-old boys: the INMA
      Granada cohort study.
AB  - BACKGROUND: Studies examining the association of anogenital distance (AGD), a
      biomarker of prenatal androgen exposure, with sexual development in children are
      lacking. OBJECTIVE: To assess the association between AGD measures and
      reproductive outcomes, including puberty onset, testicular volume, reproductive
      hormone levels, and urogenital malformations in boys aged 9-11 years. MATERIALS
      AND METHODS: A cross-sectional study was conducted among children belonging to
      the Spanish Environment and Childhood (INMA) Project, a population-based birth
      cohort study. The present sample included 279 boys for whom data were available
      on AGD, pubertal stage, testicular volume, and relevant covariates. Out of the
      boys with AGD data, 187 provided a blood sample for hormone analysis. AGD was
      measured from the center of the anus to the base of the scrotum. Pubertal
      development was assessed according to Tanner stage of genital development (G1
      G5), and testicular volume was measured with an orchidometer. RESULTS: After
      adjusting for potential confounders, logistic regression analysis showed that AGD
      was positively associated with testicular volume but not with Tanner stage (>G1
      vs. G1), serum hormone levels, or undescended testis. Regardless of their age,
      body mass index, and Tanner stage (G1 or >G1), boys with longer AGD showed
      increased odds of a testicular volume >3 mL (OR = 1.06, 95%CI = 1.00-1.19 per 10%
      increment in AGD; and OR = 3.14, 95%CI = 0.99-9.94 for AGD >42 mm vs. <33 mm).
      DISCUSSION: Longer AGD was associated with testicular growth, an indicator of
      gonadarche, but not with other reproductive outcomes. CONCLUSIONS: Although AGD
      was positively associated with testicular volume, it remains unclear whether AGD
      predicts testis size at puberty or is related to puberty onset.

PMID- 30113142
TI  - Frequency of Self-Monitoring of Blood Glucose during the School Day Is Associated
      with the Optimal Glycemic Control among Korean Adolescents with Type 1 Diabetes.
AB  - BACKGROUND: This study aimed to evaluate the relationship between the frequency
      of self-monitoring of blood glucose (SMBG) and glycosylated hemoglobin (HbA1c)
      levels among Korean adolescents with type 1 diabetes mellitus (T1DM). Factors
      affecting the SMBG frequency were analyzed in order to improve their glycemic
      control. METHODS: Sixty-one adolescents aged 13 to 18 years with T1DM were
      included from one tertiary center. Clinical and biochemical variables were
      recorded. Factors associated with SMBG frequency were assessed using structured
      self-reported questionnaires. RESULTS: Average total daily SMBG frequency was
      3.8+/-2.1 and frequency during the school day was 1.3+/-1.2. The mean HbA1c level
      was 8.6%+/-1.4%. As the daily SMBG frequency increased, HbA1c levels declined
      (P=0.001). The adjusted odds of achieving the target HbA1c in participants who
      performed daily SMBG >=5 significantly increased 9.87 folds (95% confidence
      interval [CI], 1.58 to 61.70) compared with those performed SMBG four times a
      day. In the subjects whose SMBG frequency <1/day during the school day, an 80%
      reduction in the adjusted odds ratio 0.2 (95% CI, 0.05 to 0.86) showed compared
      to the group with performing two SMBG measurements in the school setting. The
      number of SMBG testing performed at school was significantly high for individuals
      assisted by their friends (P=0.031) and for those who did SMBG in the classrooms
      (P=0.039). CONCLUSION: Higher SMBG frequency was significantly associated with
      lower HbA1c in Korean adolescents with T1DM. It would be necessary to establish
      the school environments that can facilitate adequate glycemic control, including
      frequent SMBG.

PMID- 30113143
TI  - Impact of Socioeconomic Status on Health Behaviors, Metabolic Control, and
      Chronic Complications in Type 2 Diabetes Mellitus.
AB  - BACKGROUND: The aim of the study was to assess the impact of socioeconomic status
      (SES) on health behaviors, metabolic control, and chronic complications in people
      with type 2 diabetes mellitus (T2DM) from South Korea, a country with universal
      health insurance coverage and that has experienced rapid economic and social
      transition. METHODS: A total of 3,294 Korean men and women with T2DM aged 30 to
      65 years, participating in the Korean National Diabetes Program (KNDP) cohort who
      reported their SES and had baseline clinical evaluation were included in the
      current cross-sectional analysis. SES included the level of education and monthly
      household income. RESULTS: Lower education level and lower income level were
      closely related, and both were associated with older age in men and women. Women
      and men with lower income and education level had higher carbohydrate and lower
      fat intake. After adjustment for possible confounding factors, higher education
      in men significantly lowered the odds of having uncontrolled hyperglycemia
      (glycosylated hemoglobin >=7.5%) (odds ratio [OR], 0.63; 95% confidence interval
      [CI], 0.43 to 0.91 for highest education; P(trend)=0.048), while higher household
      income in men significantly lowered the odds of having diabetic retinopathy (OR,
      0.59; 95% CI, 0.37 to 0.95 for highest income level; P(trend)=0.048). In women,
      lower income was associated with a higher stress level. CONCLUSION: Men with
      lower SES had higher odds of having diabetic retinopathy and uncontrolled
      hyperglycemia, showing the need to improve care targeted to this population.

PMID- 30113144
TI  - Development and Validation of the Korean Diabetes Risk Score: A 10-Year National
      Cohort Study.
AB  - BACKGROUND: A diabetes risk score in Korean adults was developed and validated.
      METHODS: This study used the National Health Insurance Service-National Health
      Screening Cohort (NHIS-HEALS) of 359,349 people without diabetes at baseline to
      derive an equation for predicting the risk of developing diabetes, using Cox
      proportional hazards regression models. External validation was conducted using
      data from the Korean Genome and Epidemiology Study. Calibration and
      discrimination analyses were performed separately for men and women in the
      development and validation datasets. RESULTS: During a median follow-up of 10.8
      years, 37,678 cases (event rate=10.4 per 1,000 person-years) of diabetes were
      identified in the development cohort. The risk score included age, family history
      of diabetes, alcohol intake (only in men), smoking status, physical activity, use
      of antihypertensive therapy, use of statin therapy, body mass index, systolic
      blood pressure, total cholesterol, fasting glucose, and gamma glutamyl
      transferase (only in women). The C-statistics for the models for risk at 10 years
      were 0.71 (95% confidence interval [CI], 0.70 to 0.73) for the men and 0.76 (95%
      CI, 0.75 to 0.78) for the women in the development dataset. In the validation
      dataset, the C-statistics were 0.63 (95% CI, 0.53 to 0.73) for men and 0.66 (95%
      CI, 0.55 to 0.76) for women. CONCLUSION: The Korean Diabetes Risk Score may
      identify people at high risk of developing diabetes and may be an effective tool
      for delaying or preventing the onset of condition as risk management strategies
      involving modifiable risk factors can be recommended to those identified as at
      high risk.

PMID- 30113145
TI  - Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic
      Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus.
AB  - BACKGROUND: Carotid artery intima medial thickness (IMT), brachial-ankle pulse
      wave velocity (baPWV), and ankle-brachial index (ABI) are commonly used surrogate
      markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus
      (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV,
      which is affected by blood pressure. However, it is unclear which marker is the
      most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD).
      METHODS: This was a retrospective non-interventional study that enrolled 219
      patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the
      relationship of these tests to the 10-year ASCVD risk were also analyzed.
      RESULTS: Among the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group,
      CAVI correlated significantly with IMT after adjusting for confounding variables,
      but ABI was not associated with CAVI or IMT. The analyses after dividing the non
      ASCVD group into three subgroups according to the CAVI score (<8, >=8 and <9, and
      >=9) demonstrated the significant increase in the mean IMT, 10-year ASCVD risk
      and number of metabolic syndrome risk factors, and decrease in the mean ABI in
      the high-CAVI group. A high CAVI was an independent risk factor in the non-ASCVD
      group for both a high 10-year ASCVD risk (>=7.5%; odds ratio [OR], 2.42; P<0.001)
      and atherosclerosis (mean IMT >=1 mm; OR, 1.53; P=0.007). CONCLUSION: In Korean
      patients with T2DM without ASCVD, CAVI was the most sensitive of several
      surrogate markers for the detection of subclinical atherosclerosis.

PMID- 30113147
TI  - The Prevalence and Risk Factors for Diabetic Retinopathy in Shiraz, Southern
      Iran.
AB  - Globally, diabetic retinopathy (DR) is one of the leading causes of blindness,
      that diminishes quality of life. This study aimed to describe the prevalence of
      DR, and its associated risk factors. This cross-sectional study was carried out
      among 478 diabetic patients in a referral center in Fars province, Iran. The
      mean+/-standard deviation age of the participants was 56.64+/-12.45 years old and
      DR prevalence was 32.8%. In multivariable analysis, lower education levels
      (adjusted odds ratio [aOR], 0.43; 95% confidence interval [CI], 0.24 to 0.76),
      being overweight (aOR, 1.70; 95% CI, 1.02 to 2.83) or obese (aOR, 1.88; 95% CI,
      1.09 to 3.26), diabetes duration of 10 to 20 years (aOR, 2.35; 95% CI, 1.48 to
      3.73) and over 20 years (aOR, 5.63; 95% CI, 2.97 to 10.68), receiving insulin
      (aOR, 1.99; 95% CI, 1.27 to 3.10), and having chronic diseases (aOR, 1.71; 95%
      CI, 1.02 to 2.85) were significantly associated with DR. In conclusion, longer
      diabetes duration and obesity or having chronic diseases are strongly associated
      with DR suggesting that control of these risk factors may reduce both the
      prevalence and impact of retinopathy in Iran.

PMID- 30113146
TI  - Diabetes Fact Sheet in Korea, 2016: An Appraisal of Current Status.
AB  - BACKGROUND: This report presents the recent prevalence and comorbidities related
      to diabetes in Korea by analyzing the nationally representative data. METHODS:
      Using data from the Korea National Health and Nutrition Examination Survey for
      2013 to 2014, the percentages and the total number of subjects over the age of 30
      years with diabetes and prediabetes were estimated and applied to the National
      Population Census in 2014. Diagnosis of diabetes was based on fasting plasma
      glucose (>=126 mg/dL), current taking of antidiabetic medication, history of
      previous diabetes, or glycosylated hemoglobin (HbA1c) >=6.5%. Impaired fasting
      glucose (IFG) was defined by fasting plasma glucose in the range of 100 to 125
      mg/dL among those without diabetes. RESULTS: About 4.8 million (13.7%) Korean
      adults (>=30 years old) had diabetes, and about 8.3 million (24.8%) Korean adults
      had IFG. However, 29.3% of the subjects with diabetes are not aware of their
      condition. Of the subjects with diabetes, 48.6% and 54.7% were obese and
      hypertensive, respectively, and 31.6% had hypercholesterolemia. Although most
      subjects with diabetes (89.1%) were under medical treatment, and mostly being
      treated with oral hypoglycemic agents (80.2%), 10.8% have remained untreated.
      With respect to overall glycemic control, 43.5% reached the target of HbA1c <7%,
      whereas 23.3% reached the target when the standard was set to HbA1c <6.5%,
      according to the Korean Diabetes Association guideline. CONCLUSION: Diabetes is a
      major public health threat in Korea, but a significant proportion of adults were
      not controlling their illness. We need comprehensive approaches to overcome the
      upcoming diabetes-related disease burden in Korea.

PMID- 30113149
TI  - [To promote clinical trials for muscular dystrophy].

PMID- 30113150
TI  - [The pitfalls of using diagnosis and treatment guidelines for patients with
      juvenile myasthenia gravis].
AB  - Even though evidence-based clinical guidelines are useful for the management of
      common diseases, there are several problems in applying such guidelines to
      patients with rare diseases. First, there are few references providing high-level
      evidence pertaining to such diseases, and randomized control as well as large
      cohort studies are lacking. Most grades of recommendation are "suggest" rather
      than "recommend" or, often, are based on "expert opinion". Juvenile myasthenia
      gravis (MG) is a rare disease and has mainly been reported in East Asia. In 2014,
      evidence-based clinical guidelines for MG diagnosis and treatment were published
      in Japan. Since references were scarce, these guidelines were also based on
      expert opinions such as those of a few institutes or specialists who had gathered
      most of the patients in Japan. The guidelines might be of limited usefulness for
      general pediatricians or pediatric neurologists with no MG experience, and we
      should be aware of strengths and pitfalls when applying such guidelines. For
      example, while knowing when to start steroid administration or the appropriate
      steroid dose is feasible, the optimal timing of switching from an anti
      cholinesterase drug to a steroid or adding an anti-inflammatory drug and how to
      decrease or stop steroid administration cannot be ascertained from the
      guidelines. The lack of references with high-level evidence makes the guidelines
      difficult to apply, since this would be the information most desired by
      clinicians. Another problem is that a recommendation may easily be reversed if
      opposing results are obtained in a single study of a rare disease. Thymectomy was
      recognized as not being beneficial for MG without thymoma but one recent study
      reversed this recommendation in the guidelines. Herein, we discuss pitfalls in
      applying diagnostic and treatment guidelines in patients with juvenile MG.

PMID- 30113148
TI  - The Association between Pancreatic Steatosis and Diabetic Retinopathy in Type 2
      Diabetes Mellitus Patients.
AB  - BACKGROUND: Whether pancreatic steatosis has a local or systemic effect, like
      ectopic fat of other major organs, remains unknown. Data on the influence of
      pancreatic steatosis on microvascular complication are rare. Therefore, we
      investigated the relationship between pancreatic steatosis and diabetic
      retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). METHODS: The
      attenuation of three pancreatic regions (head, body, and tail) and the spleen (S)
      in 186 patients with T2DM was measured using non-enhanced computed tomography
      imaging. We used three parameters for the assessment of pancreatic steatosis ('P'
      mean: mean attenuation of three pancreatic regions; P-S: difference between 'P'
      mean and 'S'; P/S: the 'P' mean to 'S' ratio). The presence of DR was assessed by
      an expert ophthalmologist using dilated fundoscopy. RESULTS: The average P mean
      was 29.02 Hounsfield units (HU), P-S was -18.20 HU, and P/S was 0.61. The three
      pancreatic steatosis parameters were significantly associated with the prevalence
      of DR in non-obese T2DM patients. In the non-obese group, the odds ratios of P
      mean, P-S, and P/S for the prevalence of DR, after adjustment for age, sex, and
      glycosylated hemoglobin level, were 2.449 (P=0.07), 2.639 (P=0.04), and 2.043
      (P=0.02), respectively. CONCLUSION: In this study, pancreatic steatosis was
      significantly associated with DR in non-obese patients with T2DM. Further studies
      are necessary to clarify the causal relationship between pancreatic steatosis and
      the development of DR.

PMID- 30113151
TI  - [The efficacy of intravenous alendronate for osteoporosis in patients with severe
      motor intellectual disabilities].
AB  - Objective: Bone fractures in patients with severe motor and intellectual
      disabilities (SMIDs) have become an important problem to be solved. These
      fractures may result from disuse osteoporosis. Bisphosphonate administration is
      generally the most established treatment for patients with osteoporosis. However,
      traditional oral bisphosphonate use is associated with esophagitis as a side
      effect and may increase the risk of reflux esophagitis for bedridden patients.
      Intravenous alendronate, one of the bisphosphonates, was released in 2012 in
      Japan. Though it is appropriate for patients with SMIDs, there are no reports
      about the effects of intravenous alendronate on osteoporosis in SMID patients.
      Therefore, the efficacy of intravenous alendronate for osteoporosis was
      investigated in SMID patients. Methods: The subjects were 62 SMID patients with
      osteoporosis (20 to 60 years old) in our hospital. They were divided two groups,
      bisphosphonate treatment group (32 patients) and age-matched controls (30
      patients). Patients in bisphosphonate treatment groups were given 900MUg
      intravenous alendronate once a month. All patients were also administered oral
      vitamin D3. Serial bone density, bone metabolism markers, and existence of
      fractures were compared in both groups before and after treatment (6 months, 1
      years, and 2 years). Results: In bisphosphonate treatment group, the change rate
      of bone density was significantly increased and bone metabolism markers were
      improved at 6 months and 1 year after starting treatment. After a year, 16
      patients in treatment group changed into other treatments, and 12 controls
      started bisphosphonate treatment. In remaining treatment group (16 patients), the
      change rate of bone density and bone metabolism markers were improved
      significantly at 2 years after starting treatment. A patient in control group had
      a bone fracture, but no patients in bisphosphonate treatment groups had fractures
      or severe adverse effects. Conclusion: Intravenous alendronate is an effective
      treatment for osteoporosis in SMID patients.

PMID- 30113152
TI  - [The characteristics of social skills, school maladjustment and stress responses
      in junior high school students with autism spectrum disorder].
AB  - Objective: The purpose of this study was to test difference between the social
      skills of adolescents with autism spectrum disorder (ASD) and their typically
      developing students." Methods: Participants were 299 junior high school students
      from public schools. The group included 19 junior high school students with ASD.
      Participants responded to self-rated questionnaire on social skills, school
      maladjustment, and stress. Results: Results showed that adolescent with ASD had
      mental health difficulties (in stress responses and school maladjustment) and
      poor social skills as compared to their typically developing peers. A cluster
      analysis was conducted by dividing the participants into the following four
      groups based on their z-scores on the social skills scale: "low skill type", "low
      skill of continuing relationship type", "well-balance type", and "inactive type".
      A Chi-square test revealed that a greater portion of the ASD group included
      students belonging to the "inactive, authoritative and low type" and "inactive
      type" cluster as compared to the typically developing group. Conclusions: The
      Adolescent with ASD have social skills characterized by inactive type that poor
      entry skills.

PMID- 30113153
TI  - [Irreversible cerebral ischemia caused by febrile status epilepticus in Sturge
      Weber syndrome type III].
AB  - We report a 9-year-old girl with Sturge-Weber syndrome (SWS) type III, whose
      motor function deteriorated after an episode of febrile status epilepticus. The
      patient had leptomeningeal angiomas in the left temporal, occipital, and parietal
      lobes. Complex partial seizures, which started at 8 months, were controlled by
      antiepileptic medications. At 9 years of age, she developed irreversible ischemic
      lesions in the left temporal and occipital regions after the febrile status
      epilepticus and her motor function deteriorated. In addition to antiepileptic
      medications, aspirin therapy was started.SWS type III is a rare disorder
      characterized by leptomeningeal angiomatosis without facial nevus. In addition to
      the chronic ischemia in the affected cortex, epileptic seizures result in a
      phased progression of ischemia in SWS. Although the patient's complex partial
      seizures had been well-controlled, a single episode of febrile status epilepticus
      resulted in permanent brain lesions. The impairment of appropriate hemodynamic
      response to status epilepticus, together with venous hypertension in the affected
      side in SWS may have caused the cerebral infarction in our case. Seizure control
      is crucial to improving the neurological prognosis of SWS.

PMID- 30113154
TI  - [A case of West syndrome with a deletion at chromosome 2q24.3-q31.3].
AB  - A male infant suffered from partial seizures at four months of age, and developed
      West syndrome at eight months of age. ACTH therapy was effective for the West
      syndrome. However, partial seizures recurred at 14 months of age, which could not
      be sufficiently controlled with an anti-epileptic drug. A characteristic facial
      appearance, great toe abnormalities, and developmental retardation were noted. An
      interstitial deletion of 2q was detected by chromosomal G-banding and array
      comparative genomic hybridization (CGH) confirmed the deletion as arr 2q24.3q31.3
      (166,303,447-180,982.972) *1 (build19). He presented with clinical findings
      similar to those of the recently defined 2q31.1 deletion syndrome. The deletion
      extended to the SCN1A gene, a gene responsible for Dravet syndrome, mapped to the
      2q24.3 region. No deletion was noted in the adjacent SCN2A gene. Thus, for
      interstitial deletions, detailed breakpoints should be identified by array CGH.
      The frequency of epilepsy varies with deletion ranges in the 2q24-q31 region,
      suggesting that deletions in the SCN1A gene deletion, as well as in the 2q31.1
      region, are involved in the development of West syndrome.

PMID- 30113155
TI  - [Ictal arterial spin labeling MRI findings in two cases of acute confusional
      migraine].
AB  - Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique that
      enables visualizing of cerebral blood flow without need of a contrast medium. In
      recent years, there have been reports from outside Japan related to ASL use in
      migraine attacks. We report two cases of acute confusional migraine (ACM) in
      children. At time of confusion, ASL imaging showed reduced blood flow: for the
      first patient, in both cerebral hemispheres from the occipital lobe through the
      parietal lobe to the temporal lobe; for the second patient, throughout the left
      cerebral hemisphere. T1-, T2-, diffusion-weighted images, and fluid attenuation
      inversion recovery (FLAIR) images indicated normal results. Subsequent ASL re
      examinations for both cases showed recovery from reduced blood flow. In our view,
      ACM can be characterized by a reduction in blood flow not limited to the
      occipital lobe but across wide regions of the cerebral hemisphere. We consider
      ASL to be helpful in the difficult differentiation of ACM from other disturbances
      of consciousness, in addition to enabling repeated examinations without the risks
      associated with single-photon emission computed tomography (SPECT) concerning
      radiation exposure or with contrast MRI concerning contrast media use.

PMID- 30113156
TI  - Erratum.
AB  - [This corrects the article DOI: 10.5152/TurkJOrthod.2017.17045.].

PMID- 30113157
TI  - [Non-invasive positive pressure ventilation during the management of severe
      spinal muscular atrophy type I].
AB  - Patients with spinal muscular atrophy type I (SMA I) with the onset before the
      age of 3 months are considered as severe form of SMA I (severe SMA I) and have
      poor prognosis. Here, we report the efficacy of non-invasive positive pressure
      ventilation (NPPV) in a patient with severe SMA I. She was born with generalized
      hypotonia and feeding difficulties, and had SMN1 gene mutations (the deletion of
      exons 7 and 8). At 1 month of age, she was intubated because of respiratory
      failure due to a respiratory tract infection, and extubation proved difficult.
      Her parents decided that NPPV and a mechanical in-exsufflator (MI-E) should be
      used for respiratory management rather than a tracheotomy. The NPPV improved her
      peripheral coldness, cold sweats, chest wall movement, and heart rate and enabled
      her to sleep well. At 1 year and 2 months, chest computed tomography revealed
      mild pneumonia and did not show any atelectasis. The NPPV facilitated discharge,
      and the patient had a good quality of life (QOL) from the point of view of voice
      production, the ability to move easily, the simplicity of bathing, and the low
      level of discomfort she experienced. However, she suffered repeated episodes of
      aspiration pneumonia and airway obstruction (by sputum) after 11 months of age.
      Thereafter, she required continuous NPPV and high-span inspiratory positive
      airway pressure (21 cmH2O). At 1 year and 4 months, she died of respiratory
      failure at home. As her bulbar weakness worsened, respiratory management with
      NPPV became difficult. However, the long-term use of NPPV together with high-span
      positive inspiratory pressure plus positive end-expiratory pressure, and a high
      pressure MI-E at an early age might improve respiratory management outcomes and
      patient prognosis. In our case, NPPV was effective at improving ventilation and
      preventing atelectasis and helped to provide the patient with a good QOL.

PMID- 30113158
TI  - Preparation and Characterization of Chiral Transition-Metal Dichalcogenide
      Quantum Dots and Their Enantioselective Catalysis.
AB  - Two-dimensional transition-metal dichalcogenides (TMDs) had attracted enormous
      interests owing to their extraordinary optical, physical, and chemical
      properties. Herein, we prepared for the first time a series of chiral TMD quantum
      dots (QDs) from MoS2 and WS2 bulk crystals by covalent modification with chiral
      ligands cysteine and penicillamine. The chiral TMD QDs were carefully
      investigated by spectroscopic and microscopic techniques. Their chiral optical
      activity was confirmed by distinct circular dichroism signals different to those
      of the chiral ligands. Interestingly, with the assistance of copper ions, the
      chiral QDs displayed strong and chiral selective peroxidase-like activity. Up to
      now, inorganic nanomaterials with peroxidase-like activity were tremendous but
      seldom examples with enantioselectivity. The enantioselectivity of our chiral TMD
      QDs toward chiral substrates d- and l-tyrosinol was highly up to 6.77, which was
      almost the best performance ever reported. The mechanisms of enantioselectivity
      was further investigated by quartz crystal microbalance assays. We believed that
      because of the extraordinary electronic and optical properties, the chiral TMD
      QDs should be useful for nonlinear optical materials, asymmetric catalysis,
      chiral and biological sensors, and so on.

PMID- 30113159
TI  - Bioactive Injectable Hydrogels Containing Desferrioxamine and Bioglass for
      Diabetic Wound Healing.
AB  - Diabetic wound is hard to heal mainly because of the difficulty in
      vascularization in the wound area. Accumulating results have shown that
      desferrioxamine (DFO) can promote secretion of hypoxia inducible factor-1 (HIF
      1alpha), thereby upregulating the expression of angiogenic growth factors and
      facilitating revascularization. Our preliminary study has demonstrated that Si
      ions in bioglass (BG) can upregulate vascular endothelial growth factor (VEGF)
      expression, thus promoting revascularization. It is hypothesized that the
      combined use of BG and DFO may have a synergistic effect in promoting VEGF
      expression and revascularization. To prove this, we first determined DFO
      concentration range that had no apparent cytotoxicity on human umbilical vein
      endothelial cells (HUVECs). Then, the optimal concentration of DFO promoting tube
      formation of HUVECs was determined by cell migration and tube formation assays.
      In addition, we demonstrated that combination use of BG and DFO improved the
      migration and tube formation of HUVECs as compared with the use of either BG or
      DFO alone as BG and DFO could synergistically upregulate VEGF expression.
      Furthermore, a sodium alginate hydrogel containing both BG and DFO was developed,
      and this hydrogel better facilitated diabetic skin wound healing than the use of
      either BG or DFO alone as BG and DFO in the hydrogels worked synergistically in
      promoting HIF-1alpha and VEGF expression and subsequently vascularization in the
      wound sites. Therefore, in this study, the synergistic effect in promoting
      revascularization between BG and DFO was first demonstrated and an injectable
      hydrogel simultaneously containing BG and DFO was developed for enhancing repair
      of diabetic chronic skin defects by taking advantages of the synergistic effects
      of BG and DFO in promoting revascularization. The study opens up a new prospect
      for the development of skin repair-promoting biomaterials.

PMID- 30113160
TI  - Low-Temperature Plasma-Assisted Atomic-Layer-Deposited SnO2 as an Electron
      Transport Layer in Planar Perovskite Solar Cells.
AB  - In this work, we present an extensive characterization of plasma-assisted atomic
      layer-deposited SnO2 layers, with the aim of identifying key material properties
      of SnO2 to serve as an efficient electron transport layer in perovskite solar
      cells (PSCs). Electrically resistive SnO2 films are fabricated at 50  degrees C,
      while a SnO2 film with a low electrical resistivity of 1.8 * 10-3 Omega cm, a
      carrier density of 9.6 * 1019 cm-3, and a high mobility of 36.0 cm2/V s is
      deposited at 200  degrees C. Ultraviolet photoelectron spectroscopy indicates a
      conduction band offset of ~0.69 eV at the 50  degrees C
      SnO2/Cs0.05(MA0.17FA0.83)0.95Pb(I2.7Br0.3) interface. In contrast, a negligible
      conduction band offset is found between the 200  degrees C SnO2 and the
      perovskite. Surprisingly, comparable initial power conversion efficiencies (PCEs)
      of 17.5 and 17.8% are demonstrated for the champion cells using 15 nm thick SnO2
      deposited at 50 and 200  degrees C, respectively. The latter gains in fill factor
      but loses in open-circuit voltage. Markedly, PSCs using the 200  degrees C
      compact SnO2 retain their initial performance at the maximum power point over 16
      h under continuous one-sun illumination in inert atmosphere. Instead, the cell
      with the 50  degrees C SnO2 shows a decrease in PCE of approximately 50%.

PMID- 30113163
TI  - Coordination Chemistry and QTAIM Analysis of Homoleptic Dithiocarbamate
      Complexes, M(S2CNiPr2)4 (M = Ti, Zr, Hf, Th, U, Np).
AB  - In a systematic approach to comparing the molecular structure and bonding in
      homoleptic transition-metal and actinide complexes, a series of dithiocarbamates,
      M(S2CNiPr2)4 (M = Ti, Zr, Hf, Th, U, Np), have been synthesized. These complexes
      have been characterized through spectroscopic and X-ray crystallographic
      analysis, and their bonding has been examined using density functional theory
      calculations. Computational results indicate that the covalent character
      associated with the M-S bonds shows the trend of Hf < Zr < Th < Ti < U ~ Np.

PMID- 30113162
TI  - Site Selectivity of Hydride in Early-Transition-Metal Ruddlesden-Popper
      Oxyhydrides.
AB  - Layered perovskite titanium oxyhydrides have been prepared by low-temperature
      topochemical CaH2 reduction from Ruddlesden-Popper Sr n+1Ti nO3 n+1 phases ( n =
      1, 2) and structurally characterized by combined synchrotron X-ray and neutron
      diffraction data refinements. In the single-layered Sr2TiO3.91(2)D0.14(1)
      material, hydride anions are statistically disordered with oxides on the apical
      site only, as opposed to known transition-metal oxyhydrides exhibiting a
      preferred occupation of the equatorial site. This unprecedented site selectivity
      of H- has been reproduced by periodic DFT+ U calculations, emphasizing for the
      hydride defect a difference in formation energy of 0.24 eV between equatorial and
      apical sites. In terms of electronic structure, the model system
      Sr2TiO3.875H0.125 is found to be slightly metallic and the released electron
      remains mostly delocalized over several Ti atoms. On the other hand, hydride
      anions in the double-layered Sr3Ti2O6.20H0.12 material show a clear preference
      for the bridging apical site within the perovskite slabs, as confirmed by DFT
      calculations on the Sr3Ti2O6.875H0.125 model system. Finally, the influence of
      the B-site chemical nature on the hydride site selectivity for early 3d
      transition metals is theoretically explored in the single-layered system by
      substituting vanadium for titanium. The V3+ electronic polaron is suggested to
      play a role in stabilizing H- on the equatorial site in Sr2VO4- xH x for x =
      0.125.

PMID- 30113161
TI  - Duplex-Specific Nuclease-Amplified Detection of MicroRNA Using Compact Quantum
      Dot-DNA Conjugates.
AB  - Advances in nanotechnology have provided new opportunities for the design of next
      generation nucleic acid biosensors and diagnostics. Indeed, combining advances in
      functional nanoparticles, DNA nanotechnology, and nuclease-enzyme-based
      amplification can give rise to new assays with advantageous properties. In this
      work, we developed a microRNA (miRNA) assay using bright fluorescent quantum dots
      (QDs), simple DNA probes, and the enzyme duplex-specific nuclease. We employed an
      isothermal target-recycling mechanism, where a single miRNA target triggers the
      cleavage of many DNA signal probes. The incorporation of DNA-functionalized QDs
      enabled a quantitative fluorescent readout, mediated by Forster resonance energy
      transfer (FRET)-based interaction with the DNA signal probes. Our approach splits
      the reaction in two, performing the enzyme-mediated amplification and QD-based
      detection steps separately such that each reaction could be optimized for
      performance of the active components. Target recycling gave ca. 3 orders of
      magnitude amplification, yielding highly sensitive detection with a limit of 42
      fM (or 1.2 amol) of miR-148, with excellent selectivity versus mismatched
      sequences and other miRNAs. Furthermore, we used an alternative target (miR-21)
      and FRET pair for direct and absolute quantification of miR-21 in RNA extracts
      from human cancer and normal cell lines.

PMID- 30113164
TI  - Incorporating Carbohydrates into Laboratory Curricula.
AB  - As an important but underappreciated field, carbohydrate chemistry is a critical
      topic for undergraduate students to learn. With applications to nutrition, food
      science, and diabetes, carbohydrates provide real-world relevance to students.
      This review summarizes the literature of undergraduate laboratory experiments
      which use carbohydrates since the year 2000. Experiments explore important
      chemical concepts such as synthesis, kinetics, analysis, and computational
      chemistry. Experiments designed for general chemistry, organic chemistry,
      biochemistry, and analytical chemistry at a variety of skill levels are
      presented.

PMID- 30113165
TI  - Versatile Coordination and C-C Coupling of Diphosphine-Tethered Imine Ligands
      with Ni(II) and Ni(0).
AB  - Ligands that can adapt their coordination mode to the electronic properties of a
      metal center are of interest to support catalysis or small molecule activation
      processes. In this context, the ability of imine moieties to bind in either an
      eta1(N)-fashion via sigma-donation of the lone pair or, less commonly, in an
      eta2(C,N)-fashion via pi-coordination is potentially attractive for the design of
      new metal-ligand cooperative systems. Herein, the coordination chemistry of
      chelating ligands with a diphosphine imine framework (PCNP) to nickel is
      investigated. The imine moiety binds in an eta1(N)-fashion in a Ni(II)Cl2
      complex. The uncommon eta2(C,N)-interaction is obtained in Ni(0) complexes in the
      presence of a PPh3 coligand. Increasing the bulk on the phosphine side-arms in
      the Ni(0) complexes, by substituting phenyl for o-tolyl groups, leads to a
      distinct binding mode in which only one of the phosphorus atoms is coordinated.
      In the absence of a coligand, a mixture of two different dimeric Ni(0) complexes
      is formed. In one of them, the imine adopts an uncommon eta1(N)eta2(C,N) bridging
      mode of the ligand to nickel, while the second one may involve reactivity on the
      ligand by the formation of a new C-C bond by oxidative coupling. The latter is
      supported by the isolation and structural characterization of a crystalline bis
      CO derivative featuring a C-C bond formed by oxidative coupling of two imine
      moieties.

PMID- 30113166
TI  - Potential of Fructooligosaccharides and Xylooligosaccharides as Substrates To
      Counteract the Undesirable Effects of Several Antibiotics on Elder Fecal
      Microbiota: A First in Vitro Approach.
AB  - Fructooligosaccharides (FOS) and xylooligosaccharides (XOS) were employed as
      substrates for in vitro fermentations to assess their capacity to counteract the
      effects caused by three antibiotics (ABs) at different doses on the elderly gut
      microbiota and its metabolic activity. The AB type and dose scarcely affected the
      total bacterial numbers and the microbiota composition after 24 h. However, in
      the presence of ABs, the relative percentages of Lactobacillus decreased (from
      11.4% to 3.2% in the presence of XOS1), as well as the butyrate production,
      whereas the population of Bacteroides increased significantly in the presence of
      XOS1 (from 27.5% to 55.7%). FOS were able to counteract these effects by
      increasing the butyrate production and the number of Lactobacillus, while
      maintaining the number of Bacteroides almost constant and decreasing the
      clostridia. XOS2 (mainly DP = 2-4) also showed ability to increase the
      percentages of Bifidobacterium and the production of both butyrate and acetate.

PMID- 30113167
TI  - A Series of Compounds Based on [P2W18O62]6- and Transition Metal Mixed Organic
      Ligand Complexes with High Catalytic Properties for Styrene Epoxidation.
AB  - Seven compounds based on [P2W18O62]6- ({P2W18}) were successfully prepared and
      carefully characterized. [HC5H5N][Cu(2,2'-bpy)2]2[HP2W18O62].2H2O (bpy =
      bipyridine) (1) is constructed from {P2W18} bridged by [Cu(2,2'-bpy)2]2+.
      [HC5H5N][Zn(2,2'-bpy)2]2[HP2W18O62].4H2O (1a) is isostructural and isomorphous
      with compound 1. [Cu4(2,2'-bpy)3(nic)3(OH)2(H2O)][H3P2W18O62].0.5H2O (nic =
      nicotinic acid) (2) is formed by {P2W18} and tetracopper transition metal mixed
      organic ligand complexes (TMMCs). [Cu2(2,2'-bpy)2(C2O4)]3[P2W18O62].3H2O (3) is
      made up of {P2W18} and bicopper TMMCs, [Cu6(2,2'-bpy)6(OH)6][P2W18O62].2H2O (4)
      is built up from {P2W18}, and hexacopper complexes of 2,2'-bpy and hydroxyls.
      [Cu(2,2'-bpy)(hnic)0.5][Cu3(2,2'-bpy)3(hnic)2(H2O)2][H3P2W18O62] (hnic = hydroxyl
      nicotinic acid) (5a) contains two different TMMCs. In addition, compound 5a is
      the first example of a compound that contains Cu-pi interactions. [Cu2(2,2'
      bpy)2(hnic)][H4P2W18O62]. xH2O ( x ~ 50) (5b) is based on {P2W18} and [Cu2(2,2'
      bpy)2(hnic)]2+. We discuss the mechanisms for the formations of these compounds.
      All the catalytic performances of the compounds for styrene epoxidation to
      styrene oxide are high.

PMID- 30113168
TI  - Guest-Responsive Elastic Frustration "On-Off" Switching in Flexible, Two
      Dimensional Spin Crossover Frameworks.
AB  - In this study we exploit the flexible nature of porous coordination polymers
      (PCPs) with integrated spin crossover (SCO) properties to manipulate the
      multistability of spin-state switching profiles. We previously reported the two
      dimensional Hofmann-type framework [Fe(thtrz)2Pd(CN)4].EtOH,H2O (1.EtOH,H2O), N
      thiophenylidene-4 H-1,2,4-triazol-4-amine), displaying a distinctive two-step SCO
      profile driven by extreme elastic frustration. Here, we reveal a reversible
      release mechanism for this elastic frustration via stepwise guest removal from
      the parent phase (1.EtOH,H2O -> 1.H2O -> 1.O). Parallel variable temperature
      structural and magnetic susceptibility measurements reveal a synergistic
      framework flexing and "on-off" switching of multistep SCO character concomitant
      with the onset of guest evacuation. In particular, the two-step SCO properties in
      1.EtOH,H2O are deactivated such that both the partially solvated (1.H2O) and
      desolvated (1.O) phases show abrupt and hysteretic one-step SCO behaviors with
      differing transition temperatures (1.H2O: T1/2?: 215 T1/2?: 235 K; 1.O: T1/2?:
      170 T1/2?: 182 K). This "on-off" elastic frustration switching is also reflected
      in the light-induced excited spin state trapping (LIESST) properties of
      1.EtOH,H2O and 1.O, with nonquantitative (ca. 50%, i.e., LS <-> 1:1 HS:LS) and
      quantitative (ca. 100%, LS <-> HS) photoinduced spin state conversion achieved
      under light irradiation (510 nm at 10 K), respectively. Conversely, the two-step
      SCO properties are retained in the water saturated phase 1.3H2O but with a subtle
      shift in transition temperatures. Comparative analysis of this and related
      materials reveals the distinct roles that indirect and direct guest interactions
      play in inducing, stabilizing, and quantifying elastic frustration and the
      importance of lattice flexibility in these porous framework architectures.

PMID- 30113169
TI  - Toward a Synthesis of Fawcettimine-Type Lycopodium Alkaloids: Stereocontrolled
      Synthesis of a Functionalized Azaspirocycle Precursor.
AB  - The stereocontrolled synthesis of a new azaspirocycle precursor of the
      fawcettimine-type Lycopodium alkaloids is described. Our approach provides an
      efficient entry to the azaspirocycle via a cascade Wacker-allylation sequence
      followed by a highly stereoselective Claisen rearrangement. This azaspirocycle,
      bearing all of the requisite functionality with pivotal stereogenic centers, is
      considered to be a versatile precursor useful for the fawcettimine-type
      Lycopodium alkaloids.

PMID- 30113170
TI  - Identification of Missing Proteins in Human Olfactory Epithelial Tissue by Liquid
      Chromatography-Tandem Mass Spectrometry.
AB  - We performed proteomic analyses of human olfactory epithelial tissue to identify
      missing proteins using liquid chromatography-tandem mass spectrometry. Using a
      next-generation proteomic pipeline with a < 1.0% false discovery rate at the
      peptide and protein levels, we identified 3731 proteins, among which five were
      missing proteins (P0C7M7, P46721, P59826, Q658L1, and Q8N434). We validated the
      identified missing proteins using the corresponding synthetic peptides. No
      olfactory receptor (OR) proteins were detected in olfactory tissue, suggesting
      that detection of ORs would be very difficult. We also identified 49 and 50
      alternative splicing variants mapped at the neXtProt and GENCODE databases,
      respectively, and 2000 additional single amino acid variants. This data set is
      available at the ProteomeXchange consortium via PRIDE repository (PXD010025).

PMID- 30113171
TI  - Correction to An Inexpensive and Scalable Synthesis of Shld.

PMID- 30113172
TI  - Galactose-Functionalized Double-Hydrophilic Block Glycopolymers and Their
      Thermoresponsive Self-Assembly Dynamics.
AB  - Glycopolymers with large galactose units are attractive in biological processes
      because of their ability to selectively recognize lectin proteins. Recently,
      thermoresponsive double-hydrophilic block glycopolymers (TDHBGs) have been
      designed, which allow sugar residues to expose or hide via the lower critical
      solution temperature (LCST)-type phase transition. In this work, we first
      synthesize a new type of TDHBGs, composed of a thermoresponsive poly(di(ethylene
      glycol)methyl ether methacrylate) block and a galactose-functionalized, poly(6- O
      vinyladipoyl-d-galactose) (POVNG) block. The LCST can be tuned by varying the
      size of the POVNG block. Then, we have systematically investigated their
      thermoresponsive self-assembly behavior, using static and dynamic light
      scattering techniques, combined with transmission electron microscopy (TEM)
      imaging. It is found that the TDHBGs possess both micellization and LCST-type
      transition, and there exist strong interactions between them, depending on the
      concentration and structure of the TDHBGs. It is particularly interesting that
      for the same type of TDHBGs under different conditions, such interactions result
      in rich morphologies of the formed micelles (or nanoparticles) such as spheres,
      hollow spheres, prolate ellipsoids, crystal-like, and so on, thus potentially
      enriching their biological applications by noting that they are hepatoma
      targeting glycopolymers.

PMID- 30113173
TI  - Copper-Catalyzed Synthesis of Hindered Ethers from alpha-Bromo Carbonyl
      Compounds.
AB  - A catalytic method for the synthesis of sterically hindered ethers and thioethers
      from alpha-bromo carbonyl compounds and the corresponding nucleophiles using an
      inexpensive Cu(I) catalytic system is reported. This facile transformation takes
      place at ambient temperature and does not require the exclusion of air or
      moisture; thus, it is well-suited for the functionalization and derivatization of
      complex organic molecules.

PMID- 30113175
TI  - Transracially adoptive parents' colorblindness and discrimination recognition:
      Adoption stigma as moderator.
AB  - OBJECTIVES: In a sample of transracially adoptive parents, this study examined
      the moderating role of adoption stigma in the relationship between their
      colorblind attitudes and their perceptions of different forms of discrimination.
      Specifically, we hypothesized that parents' colorblind attitudes would be
      negatively related to their perceptions of their adopted children's experiences
      with racism and their views toward racial microaggressions and institutional
      racism. We also hypothesized that perceived adoption stigma would moderate these
      relationships, such that the inverse association between colorblindness and the 3
      outcome variables would be weakened by adoption stigma. METHOD: A total of 172
      White parents (Mage = 48.41) with adopted children of color participated in the
      study by completing questionnaires about their experiences as transracially
      adoptive parents. Women comprised 74% of participants. RESULTS: Results indicated
      that the relationship between participants' colorblind attitudes and their
      reports of adoptees' racist experiences was enhanced at nearly all levels
      perceived adoption stigma. In addition, results revealed that at high levels of
      perceived adoption stigma (75th and 90th percentiles), the magnitude of the
      relationships between colorblind attitudes with microaggressions and
      institutional discrimination was significantly reduced and became nonsignificant
      for parents with younger adoptees but not older adoptees. CONCLUSIONS: Findings
      point to the potential benefits of helping transracially adoptive parents explore
      different dimensions of their own social-cultural identity as a way to enhance
      their ability to recognize different forms of discrimination that their adopted
      children may face. (PsycINFO Database Record

PMID- 30113174
TI  - Hedyorienoids A and B, Two Sesquiterpenoid Dimers Featuring Different Polycyclic
      Skeletons from Hedyosmum orientale.
AB  - Hedyorienoids A (1) and B (2), two sesquiterpenoid dimers, were isolated and
      characterized from Hedyosmum orientale. Compound 1 was an unprecedented
      heterodimer of two different classes of sesquiterpenoids furnished by forming an
      unusual 1,3-dioxolane ring, while compound 2 possessed a new dimerization pattern
      of two guaiane-type sesquiterpenoids. Biosynthetic pathways for 1 and 2 were
      proposed with the coexisting monomers chloranthalactone A (3) and hedyosumin A
      (4) as the precursors. Compounds 2 and 3 showed significant NF-kappaB inhibitory
      activity.

PMID- 30113176
TI  - Before the deluge: The 1932 International Congress of Psychology in Copenhagen.
AB  - The Tenth International Congress of Psychology, held in Copenhagen in late August
      of 1932, was the last International Congress held before events leading up to
      World War II came to interfere with the course of the congresses. Despite the
      difficult times, primarily because of the Great Depression and the fragile
      political situation, the congress nevertheless managed to bring together
      participants from many countries, thus emphasizing the international profile of
      psychology. The 1932 congress was characterized by the wide range of topics
      presented and discussed. A book of proceedings, containing all the papers
      delivered, was planned but never appeared, as the organizers of the congress were
      unable to obtain funds required for the publication. Therefore, relatively little
      has been written about the congress. The congress, however, aroused great
      interest in the Danish newspapers. Many participants took part in interviews,
      casting an interesting light on their approaches to psychology. The newspaper
      reports, along with archival sources, make it possible to describe the course of
      the conference. It clearly emerges that psychology had, by this time, shed the
      narrow experimental focus of its earliest decades. The gathering clouds of
      international unrest had some effects on the course of the congress. Shortly
      after the congress, the careers and even the lives of many of the participants
      faced serious challenges. (PsycINFO Database Record

PMID- 30113177
TI  - Ostracism, attributions, and their relationships with international students' and
      employees' outcomes: The moderating effect of perceived harming intent.
AB  - The two studies reported in this article tested the relationships among
      ostracism, attributions of ostracism, and the victims' outcomes. I examined the
      moderating effect of perceived harming intent on these mediational relationships.
      Study 1 used online survey design and was based on a group of 150 international
      students who studied in the United States. Ostracism was positively related to
      both internal and external attributions. Internal attribution was more strongly
      negatively related to self-esteem than was external attribution. Perceived
      harming intent moderated the relationship between ostracism and internal
      attribution. International students made more internal attributions when the
      perceived harming was low rather than high. Study 2 used time-lagged online
      survey design and was based on data from 403 (Time 1, N = 236 at Time 2) full
      time employees. Employees made both internal and external attributions of
      ostracism. Internal attribution was more strongly related to employee outcomes
      (i.e., lower self-esteem, higher depression, psychological strains, physical
      strains, and absence) than was external attribution. Perceived harming intent of
      ostracism moderated ostracism in relation to both internal and external
      attributions. Employees made more internal attributions when perceived harming
      intent was low (i.e., nonpurposeful ostracism); they made more external
      attributions when perceived harming intent was high (i.e., purposeful ostracism).
      Both studies provided support to the moderated mediation model in which the
      indirect effect of ostracism on employee outcomes via internal attribution was
      dependent upon the level of perceived harming intent. (PsycINFO Database Record

PMID- 30113179
TI  - Visual attention, indicative gestures, and calls accompanying gestural
      communication are associated with sociality in wild chimpanzees (Pan troglodytes
      schweinfurthii).
AB  - The challenges of life in complex social groups may select for complex
      communication to regulate interactions among conspecifics. Whereas the
      association between social living and vocalizations has been explored in nonhuman
      primates, great apes also have a rich repertoire of gestures, and how the
      complexity of gestural communication relates to sociality is still unclear. We
      used social network analysis to examine the relationship between the duration of
      time pairs of chimpanzees spent in proximity (within 10 m) and the rates of
      gestural communication accompanied by visual attention of the signaler, one-to
      one calls, indicative gestures (collectively self-relevance cues), and
      synchronized pant-hoot calls. Pairs of chimpanzees that spent a longer duration
      of time in proximity had a higher rate of visual gestures accompanied by these
      behaviors. Further, individual chimpanzees that had a greater number of proximity
      bonds had a larger social network maintained through gestures accompanied by
      synchronized pant-hoot calls. In contrast, gestures unaccompanied by these
      behaviors were not positively associated with either proximity bonds in pairs of
      chimpanzees or individual differences in sociality. These results suggest that
      self-relevance cues and synchronized pant-hoot calls accompanying gestures may
      increase the efficiency of gestural communication in social bonding and that
      multimodal communication may have played a key role in language evolution.
      (PsycINFO Database Record

PMID- 30113178
TI  - Worksite physical activity intervention and somatic symptoms burden: The role of
      coworker support for basic psychological needs and autonomous motivation.
AB  - Suffering from somatic symptoms can seriously hamper one's quality of life and
      ability to function, causing lost work productivity, sickness absence, and
      extensive medical utilization. Physical activity (PA) has demonstrated promising
      results related to mild to moderate cases of somatic symptoms. The present study
      explored whether a worksite health promotion intervention was able to increase PA
      and cardiorespiratory fitness, and to reduce somatic symptoms and sickness
      absence. The intervention was designed based on the tenets of Self-determination
      theory. A pre-post cluster randomized controlled trial was conducted with 202
      industrial workers in a Norwegian logistics company. Results from repeated
      measures, multivariate analysis of variance, revealed an overall intervention
      effect and significant change between groups related to somatic symptoms in favor
      of the intervention group, albeit no significant change in sickness absence. We
      applied structural equations modeling to test a model of health behavioral
      change, which posited that increased support for PA from coworkers and autonomous
      motivation for PA predicted changes in PA, cardiorespiratory fitness, and somatic
      symptoms. The results underline the effectiveness of including coworker social
      support in health promotion programs aimed to increase PA and reduce somatic
      symptoms. (PsycINFO Database Record

PMID- 30113180
TI  - The effects of routine outcome monitoring (ROM) on therapy outcomes in the course
      of an implementation process: A randomized clinical trial.
AB  - This study investigated the effects of the Partners for Change Outcome Management
      System (PCOMS) in adult outpatient treatment at a hospital-based mental health
      clinic. It also investigated whether the effects differed with the timing of the
      treatment within a 4-year implementation period, with clients' initial distress
      levels, and between therapists. Adult clients (N = 170) were randomized to
      treatment as usual (TAU) or routine outcome monitoring (ROM). Twenty therapists
      provided therapy in both conditions. Therapy outcome was measured by the Behavior
      and Symptoms Identification Scale (BASIS-32). Data were analyzed in a series of
      multilevel models (MLMs). Clients in the ROM condition were 2.5 times more likely
      to demonstrate improvement than those in the TAU condition. Controlling for
      therapist variability, the overall effect size (ES) in favor of ROM was small (d
      = 0.26, p = .037). The superiority for ROM over TAU increased significantly over
      the duration of the study. ROM effects were not moderated by clients' initial
      distress levels. Differences between therapists accounted for 9%-10% of the
      variability in outcomes, and there were no significant differences in ROM effects
      between therapists. ROM was associated with better treatment outcomes independent
      of clients' initial distress levels. Clients treated later in the study
      benefitted more from ROM than those treated earlier. (PsycINFO Database Record
      (c) 2018 APA, all rights reserved).

PMID- 30113181
TI  - "Determining optimal parameters of the self-referent encoding task: A large-scale
      examination of self-referent cognition and depression": Correction to Dainer-Best
      et al. (2018).
AB  - Reports an error in "Determining optimal parameters of the self-referent encoding
      task: A large-scale examination of self-referent cognition and depression" by
      Justin Dainer-Best, Hae Yeon Lee, Jason D. Shumake, David S. Yeager and
      Christopher G. Beevers (Psychological Assessment, Advanced Online Publication,
      Jun 07, 2018, np). In this article, there was an error in how exclusions for one
      of the three samples were reported, which resulted in inaccurate reporting of how
      many participants did not have complete data. This error did not change the
      primary results of the article or the conclusions. However, in the second
      paragraph of the Participant Attrition and Data Filtering section, the number of
      exclusions for the adolescent sample should be 301, not 163. As a result, n=408
      should read n=270 in the abstract; in paragraph 3 of the Method section; and in
      the Figure 1 legend. In addition, the correct values for the Adolescents sample
      reported in Tables 1 and 2 are provided in the erratum. (The following abstract
      of the original article appeared in record 2018-25404-001.) Although the self
      referent encoding task (SRET) is commonly used to measure self-referent cognition
      in depression, many different SRET metrics can be obtained. The current study
      used best subsets regression with cross-validation and independent test samples
      to identify the SRET metrics most reliably associated with depression symptoms in
      three large samples: a college student sample (n = 572), a sample of adults from
      Amazon Mechanical Turk (n = 293), and an adolescent sample from a school field
      study (n = 408). Across all 3 samples, SRET metrics associated most strongly with
      depression severity included number of words endorsed as self-descriptive and
      rate of accumulation of information required to decide whether adjectives were
      self-descriptive (i.e., drift rate). These metrics had strong intratask and split
      half reliability and high test-retest reliability across a 1-week period. Recall
      of SRET stimuli and traditional reaction time (RT) metrics were not robustly
      associated with depression severity. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30113182
TI  - Latent factor structure of DSM-5 posttraumatic stress disorder: Evaluation of
      method variance and construct validity of novel symptom clusters.
AB  - [Correction Notice: An Erratum for this article was reported online in
      Psychological Assessment on Nov 19 2018 (see record 2018-60122-001). In the
      article, the affiliations of multiple authors were incorrectly listed in the
      author byline and author note. For Daniel J. Lee, Michelle J. Bovin, Denise M.
      Sloan, Terence M. Keane, and Brian P. Marx, the affiliations should have read
      "National Center for PTSD, Boston, Massachusetts; VA Boston Healthcare System,
      Boston, Massachusetts; and Department of Psychiatry, Boston University School of
      Medicine." For author Paula P. Schnurr, the affiliations should have read
      "National Center for PTSD, White River Junction, Vermont; Department of
      Psychiatry, Geisel School of Medicine at Dartmouth." All versions of this article
      have been corrected.] The Diagnostic and Statistical Manual of Mental Disorders,
      Fifth Edition (DSM-5) 4-factor model of posttraumatic stress disorder (PTSD) has
      demonstrated adequate fit in several confirmatory factor analysis (CFA) studies.
      Although several alternative measurement models have demonstrated better fit,
      there is no consensus yet on the best model, and newly proposed models lack
      sufficient construct validation. Notably, these studies have relied exclusively
      on questionnaire data, and thus their findings may be attributable to a method
      effect. This study examined the factor structure of DSM-5 PTSD symptoms using
      both questionnaire and interview data to determine the impact of assessment
      method on factor structure and construct validity of alternative model symptom
      clusters. Participants (N = 380) were veterans who completed the PTSD Checklist
      for DSM-5 (PCL-5; Weathers et al., 2013) and the Clinician-Administered PTSD
      Scale for DSM-5 (CAPS-5; Weathers et al., 2013). Fit was similar across models.
      However, the seven-factor Hybrid model (Armour et al., 2015) fit best. Limited
      evidence of a method effect was observed. Results of construct validity analyses
      were mixed; some of the newly proposed symptom clusters demonstrated hypothesized
      differential associations with external correlates, but others did not. These
      findings suggest that results of previous DSM-5 PTSD CFAs supporting the Hybrid
      model are not attributable to a method effect. However, observed limited
      difference in model fit and mixed construct validity evidence raise concerns
      regarding the value of parsing DSM-5 symptom clusters. Constructs implied by the
      new factors in the more complex measurement models of PTSD require greater
      explication and construct validation. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30113183
TI  - Is perceived criticism an independent construct? Evidence for divergent validity
      across two samples.
AB  - Perceived criticism (PC) is a predictor of poor outcomes across a range of
      psychological disorders. Yet what is being measured when people are asked to
      report on how critical a key individual is of them is far from clear. In two
      community-based studies, we examined the divergent validity of PC in relation to
      measures of personality, psychopathology, early experiences with parents, and
      other cognitive and affective variables. In Study 1, an unselected sample of
      participants completed measures in the laboratory. In Study 2, participants were
      required to be married or partnered, and measures were completed online. Across
      both studies, PC was not consistently or reliably related to any measure. This
      suggests that PC may not simply be a proxy for another variable. Rather, our
      findings suggest that PC may be an independent construct worthy of research and
      clinical attention in its own right. (PsycINFO Database Record

PMID- 30113184
TI  - Nonlinear growth curve modeling using penalized spline models: A gentle
      introduction.
AB  - This didactic article aims to provide a gentle introduction to penalized splines
      as a way of estimating nonlinear growth curves in which many observations are
      collected over time on a single or multiple individuals. We begin by presenting
      piecewise linear models in which the time domain of the data is divided into
      consecutive phases and a separate linear regression line is fitted in each phase.
      Linear splines add the feature that the regression lines fitted in adjacent
      phases are always joined at the boundary so there is no discontinuity in level
      between phases. Splines are highly flexible raising the fundamental tradeoff
      between model fit and smoothness of the curve. Penalized spline models address
      this tradeoff by introducing a penalty term to achieve balance between fit and
      smoothness. The linear mixed-effects model, familiar from multilevel analysis, is
      introduced as a method for estimating penalized spline models. Higher order
      spline models using quadratic or cubic functions which further enhance a smooth
      fit are introduced. Technical issues in estimation, hypothesis testing, and
      constructing confidence intervals for higher order penalized spline models are
      considered. We then use data from the Early Childhood Longitudinal Study to
      illustrate each step in fitting a higher order penalized spline model, and to
      illustrate hypothesis testing, the construction of confidence intervals, and the
      comparison of the functions in 2 groups (boys and girls). Extensive graphical
      illustrations are provided throughout. Annotated computer scripts using the R
      package nlme are provided in online supplemental materials. (PsycINFO Database
      Record

PMID- 30113185
TI  - Pierced identities: Body modification, borderline personality features, identity,
      and self-concept disturbances.
AB  - Little is known about the connection between body modification and borderline
      personality disorder (BPD). This study investigated the relation between a wide
      range of body modification practices (piercing, tattooing, scarification, pubic
      hair removal, and cosmetic surgery) and BPD features, with a special focus on
      identity and identity dysfunction, in an adult community sample (N = 330).
      Results indicated BPD features were positively correlated with total number of
      body modifications and breadth of body modification practices endorsed, as well
      as, specifically, increased piercings, tattoos, and scarifications. Furthermore,
      identity problems (i.e., identity diffusion and low self-concept clarity) were
      associated with body modifications. Implications of these findings are discussed,
      including their heuristic value in understanding body modification in light of
      its connection to BPD (and particularly identity/self-concept functions).
      (PsycINFO Database Record

PMID- 30113186
TI  - Patients with borderline personality disorder show increased agency in life
      stories after 12 months of psychotherapy.
AB  - Patients with borderline personality disorder (BPD) display disturbances in self
      and other understanding, which is also evident when they narrate events from
      their own and significant others' lives. In a recent study, we found that
      patients described both their own and their parents' life stories as more
      negative and with fewer themes of agency and communion fulfillment. Hence, we
      examined whether 12 months of psychotherapy would change how patients described
      their own and their parents' life stories. At baseline, 30 BPD patients and 30
      matched control participants described and answered questions about their
      personal and their parents' life stories. At follow-up, 23 patients and 23
      control participants repeated the same procedure after patients had completed 12
      months of psychotherapy. At both baseline and follow-up, the life stories were
      coded for complexity and themes of agency, communion, communion fulfillment, and
      self-other confusion. BPD patients' personal life stories increased significantly
      in agency from baseline to follow-up compared with the control group, whereas
      other aspects of personal and parents' life stories did not change significantly
      after therapy. Development of agency through the reconstruction of personal life
      stories may be a crucial mechanism in psychotherapy with BPD patients. (PsycINFO
      Database Record

PMID- 30113187
TI  - Latent factor structure of PTSD symptoms in veterans with a history of mild
      traumatic brain injury and close-range blast exposure.
AB  - OBJECTIVE: Confirmatory factor analysis (CFA) has previously been employed to
      examine the latent factor structure of posttraumatic stress disorder (PTSD)
      symptoms with mixed results. A limited number of studies examined PTSD factor
      structure among veterans of recent military conflicts. This study examined the
      relationship between PTSD factor structure and the hallmark conditions of these
      conflicts, mild traumatic brain injury (mTBI) and close-range blast exposure
      (CBE). METHOD: The fit of previously proposed PTSD factor models was compared in
      a cohort of 387 combat-exposed veterans, with stratified analyses comparing
      factor structure models between those with a history of military-related mTBI and
      CBE (n = 106) and those without either of these antecedents (n = 151). CFAs were
      conducted using criteria from the Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994). RESULTS: The
      4-factor emotional numbing (EN) model yielded the best fit when using a clinician
      administered assessment of PTSD symptoms regardless of mTBI/CBE exposure status.
      However, when using a self-report measure of PTSD symptom severity, the EN model
      yielded best fit for those with mTBI/CBE exposure history while the 5-factor
      dysphoric arousal (DA) model was preferable among combat-exposed veterans with no
      history of mTBI/CBE exposure. CONCLUSIONS: Factors including mTBI and blast
      exposure and type of assessment tools must be considered when determining
      preferable PTSD latent factor structure models. (PsycINFO Database Record

PMID- 30113188
TI  - Examining posttraumatic growth and mental health difficulties in the aftermath of
      Hurricane Sandy.
AB  - OBJECTIVE: Hurricane Sandy continues to affect the mental health of New York
      residents. This study examined associations between Posttraumatic Growth (PTG)
      and mental health difficulties (MHD) including symptoms of anxiety, depression,
      and posttraumatic stress disorder (PTSD). METHOD: Participants (N = 1,356)
      recruited from the New York metropolitan area completed questionnaires regarding
      their PTG, demographics, MHD, and hurricane experiences. A weighted least squares
      regression assessed the association between MHD and PTG. A post hoc analysis
      determined whether anxiety or depression moderated the effect of PTSD on PTG.
      RESULTS: All MHD were crudely associated with greater PTG. After adjustment, an
      increased PTSD score was significantly associated with a 0.20 unit increase in
      PTG (t = 6.05, p < .001); this did not hold for depression or anxiety symptoms.
      Higher PTG was associated with being non-White (B = 5.90, t = 6.49, p < .001),
      Hispanic (B = 3.38, t = 2.89, p = .004), a smoker (B = 3.18, t = 3.28, p = .001),
      and greater Hurricane Sandy exposure (t = 7.11, p < .001). The positive
      association between PTSD symptoms and PTG was weaker among participants with
      probable depression. CONCLUSION: Results suggest that participants with higher
      PTSD symptoms were more likely to grow from the impact of the storm, indicating
      resilience. Highly exposed participants were more likely to experience PTG. A
      decrease in PTG was found among those with both PTSD and depression symptoms. The
      development and implementation of interventions fostering PTG could be beneficial
      in clinical disaster response work. (PsycINFO Database Record

PMID- 30113189
TI  - The effectiveness of army field manual interrogation approaches for educing
      information and building rapport.
AB  - In 2016, the U.S. Congress mandated that federal intelligence interrogators
      adhere to the methods of the U.S. Army Field Manual FM 2-22.3 (AFM) and that the
      manual be revised based upon empirically based evaluations of the interrogation
      methods' effectiveness with interviewees motivated to withhold information. In
      the present study, 120 participants took part in a testing situation in which
      half were induced to cheat. All participants were then accused of cheating and
      interrogated with either (a) a combination of AFM interrogation approaches that
      focused on the potential benefits of cooperation with the interviewer
      (cooperation-focused condition), or (b) a combination of AFM approaches that
      focused on the potential risks of withholding information (withholding-focused
      condition). Participants who cheated on the test were significantly more likely
      to admit their wrongdoing and to provide additional relevant information when
      interrogated with the withholding-focused approaches than when questioned with
      the cooperation-focused approaches. The "we know all" AFM approach was especially
      effective for eliciting truthful admission-related details. Participants reported
      high rapport with the interrogator in both the cooperation-focused and
      withholding-focused conditions. These findings indicate that the we-know-all
      approach can be effective for maintaining rapport and eliciting accurate
      information in brief interrogations. (PsycINFO Database Record (c) 2018 APA, all
      rights reserved).

PMID- 30113190
TI  - Reconsidering risk assessment with insanity acquittees.
AB  - States continue to rely on conditional release (CR) as an effective and cost
      effective way to manage individuals found not guilty by reason of insanity
      (NGRI). Research has demonstrated that insanity acquittees returning to the
      community have low recidivism rates and moderately low revocation rates. This
      study followed 238 individuals found NGRI in Oregon who were evaluated with the
      Historical, Clinical, Risk-20 (HCR-20; Webster, Douglas, Eaves, & Hart, 1997) and
      placed in the community on CR. The majority of individuals on CR (n = 157, 66%)
      maintained their release throughout the entire follow-up period (between 4 and 9
      years), but 81 (33.6%) had their release revoked during the follow up. In
      considering the efficacy of violence risk assessment in predicting CR outcome
      with NGRI acquittees, the HCR-20 was mostly unrelated to CR outcome. Only two
      items from the HCR-20, both from the Risk Management scale (exposure to
      destabilizers and stress) predicted revocation, but not imminence to CR
      revocation. This paper reconsiders how risk assessments are utilized with
      insanity acquittees and provides a roadmap for improving risk assessments with
      this unique population by relying on risk assessment results to plan effective
      interventions to reduce the likelihood of revocation and violence. (PsycINFO
      Database Record (c) 2018 APA, all rights reserved).

PMID- 30113191
TI  - To lead or to be liked: When prestige-oriented leaders prioritize popularity over
      performance.
AB  - Leaders often are faced with making difficult decisions for their group, such as
      when a course of action preferred by group members conflicts with one that is
      likely to optimize group success. Across 5 experiments (N = 1110), we provide
      evidence that a psychological orientation toward prestige (but not dominance)
      causes leaders to adhere publicly to group members' desires at the expense of
      group task outcomes-to prioritize popularity over performance. Experiments 1-3
      demonstrated that, in private, prestige-oriented leaders chose what they saw as
      best for group performance but that, in public, they chose whichever option was
      preferred by members of their group. In private, prestige-oriented leaders'
      tendency to choose the performance-enhancing option was mediated by group
      performance motives; in public, their adherence to group preferences was mediated
      by social approval motives. Experiments 4 and 5 advanced the investigation by
      using experimental manipulations to prime an orientation toward prestige.
      Findings replicated those from the earlier studies: participants primed with a
      prestige orientation prioritized popularity over performance. Results illuminate
      the conditions under which "good" leaders might make poor decisions. (PsycINFO
      Database Record

PMID- 30113192
TI  - On being forgotten: Memory and forgetting serve as signals of interpersonal
      importance.
AB  - Our memories contain a wealth of social information-including details of past
      interactions, facts about others, and others' identities. Yet, human memory is
      imperfect, and we often find ourselves unable to recall such information in
      social interactions. Conversely, people routinely find themselves on the
      receiving end of others' memory failures; that is, people sometimes find
      themselves forgotten. Despite the apparent pervasiveness of such experiences,
      modern science possesses no explanatory framework for understanding the
      psychological impact of being forgotten in part or in whole. Here, we propose
      that evidence of memory in social interactions is a powerful signal of the
      subjective importance attached to an object of memory and that interpretation of
      such signals has important consequences for interpersonal relationships. We
      further proposed that attributional explanations for forgetting and that the
      closeness of the relationship between the people involved in forgetting might
      moderate the impact of being forgotten. We tested this framework in four studies
      examining the experience of being forgotten in daily life (Study 1), in
      experimentally controlled firsthand encounters (Study 2), and in third party
      perceptions of forgetting (Studies 3 and 4). Results converged to support our
      proposed framework as well as the moderating role of attribution. Surprisingly,
      we found no evidence supporting the moderating role of initial relationships
      closeness. These results advance a systematic model of an understudied but
      important phenomenon and suggest rich and varied avenues of additional
      exploration. (PsycINFO Database Record

PMID- 30113193
TI  - Implicitly imprinting the past on the present: Automatic partner attitudes and
      the transition to parenthood.
AB  - A new model is proposed to explain how automatic partner attitudes affect how
      couples cope with major life transitions. The automatic partner attitudes in
      transition (APAT) model assumes that people simultaneously possess contextualized
      automatic attitudes toward their partner that can differ substantively in valence
      pre- and posttransition. It further assumes that evaluatively inconsistent pre-
      and posttransition automatic partner attitudes elicit heightened behavioral angst
      or uncertainty, self-protective behavior in response to risk, and relationship
      distress. A longitudinal study of the transition to first parenthood supported
      the model. People with evaluatively inconsistent automatic partner attitudes,
      whether more negative pretransition and positive posttransition, or more positive
      pretransition and negative posttransition, exhibited heightened evidence of
      cardiovascular threat discussing conflicts, increased self-protective behavior in
      response to parenting-related transgressions in daily interaction, and steeper
      declines in relationship well-being in the year following the transition to
      parenthood. (PsycINFO Database Record

PMID- 30113194
TI  - Sixteen going on sixty-six: A longitudinal study of personality stability and
      change across 50 years.
AB  - How much do people's personalities change or remain stable from high school to
      retirement? To address these questions, we used a large U.S. sample (N = 1,795)
      that assessed people's personality traits in adolescence and 50 years later. We
      also used 2 independent samples, 1 cross-sectional and 1 short-term longitudinal
      (N = 3,934 and N = 38, respectively), to validate the personality scales and
      estimate measurement error. This was the first study to test personality
      stability/change over a 50-year time span in which the same data source was
      tapped (i.e., self-report). This allowed us to use 4 different methods (rank
      order stability, mean-level change, individual-level change, and profile
      stability) answering different developmental questions. We also systematically
      tested gender differences. We found that the average rank-order stability was .31
      (corrected for measurement error) and .23 (uncorrected). The average mean-level
      change was half of a standard deviation across personality traits, and the
      pattern of change showed maturation. Individual-level change also supported
      maturation, with 20% to 60% of the people showing reliable change within each
      trait. We tested 3 aspects of personality profile stability, and found that
      overall personality profile stability was .37, distinctive profile stability was
      .17, and profile normativeness was .51 at baseline and .62 at the follow-up.
      Gender played little role in personality development across the life span. Our
      findings suggest that personality has a stable component across the life span,
      both at the trait level and at the profile level, and that personality is also
      malleable and people mature as they age. (PsycINFO Database Record

PMID- 30113195
TI  - Underlying wishes and nudged choices.
AB  - Is the inferred preference of a deceased relative to donate his or her organs
      stronger when the choice was made under a mandated rather than under an automatic
      default (i.e., nudged choice) legislative system? The answer to this is
      particularly important, because families can, and do, veto the choices of their
      deceased relatives. In three studies, we asked American and European participants
      from countries that have either a default opt-in or a default opt-out system to
      take on the role of a third party to judge the likelihood that an individual's
      "true wish" was to actually donate his or her organs, given that the decedent was
      registered to donate on the organ donation register. In each study participants
      were randomly assigned to one of four organ donation legislative systems (default
      opt-in, default opt-out, mandated choice, mandatory). Overall, regardless of
      which country participants came from, they perceived the donor's underlying
      preference to donate as stronger under the default opt-in and mandated choice
      systems as compared with the default opt-out and mandatory donor systems. We
      discuss the practical issues that result from using default systems in the domain
      of organ donation and propose potential ways to ameliorate the uncertainty around
      inferences of underlying preference from a nudged choice. (PsycINFO Database
      Record (c) 2018 APA, all rights reserved).

PMID- 30113196
TI  - Is there hindsight bias without real hindsight? Conjectures are sufficient to
      elicit hindsight bias.
AB  - After learning about an event, people often mistakenly believe to have predicted
      what happened all along (hindsight bias). However, what if what has happened is
      not known, but subject to conjecture? Could conjectures, in the absence of
      knowledge about the event, elicit the same bias and make people believe they
      "conjectured it all along", too? We examined this question in 2 studies.
      Immediately after the disappearance of flight MH370 in March, 2014, we asked N =
      432 individuals about the likelihood of a number of possible events. One year
      later, N = 100 of these individuals participated again and were randomly assigned
      to 2 experimental conditions. Participants in the current conjecture group
      answered the same questions from their current perspective, participants in the
      reproduced conjecture group were asked to reproduce their earlier estimates.
      Results show that conjectures had changed over time and affected participants'
      reproductions of their earlier estimates. We replicated this finding in a
      controlled lab experiment (N = 94) and found a comparable magnitude of conjecture
      based and knowledge-based hindsight bias. These findings demonstrate hindsight
      distortions in the absence of definite knowledge and extend theoretical
      assumptions about the prerequisites of hindsight bias in the context of events.
      (PsycINFO Database Record

PMID- 30113197
TI  - Delivering problem-solving treatment in low-vision rehabilitation: A pilot
      feasibility study.
AB  - PURPOSE: To explore the feasibility and preliminary effectiveness of Problem
      Solving Treatment for Primary Care (PST-PC) delivered by low-vision
      rehabilitation (LVR) practitioners to adult clients with depressive symptoms.
      DESIGN/METHOD: A single-group pre/postintervention study. Eighteen adult LVR
      clients with depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] score of
      >=5) received 6-8 weekly telephone sessions of PST-PC delivered by expertly
      trained practitioners (n = 14). Feasibility was determined via participating
      client and practitioner recruitment and intervention retention rates. Depressive
      symptoms (PHQ-9), health-related quality of life (HRQoL; Assessment of QoL
      Instrument-7D), and confidence in one's ability to cope using problem-solving
      strategies (Coping Self-Efficacy Scale) were assessed using pre/posttelephone
      assessments. RESULTS: Participating client recruitment and retention rates were
      71% and 40%, respectively. Seventy percent of practitioners completed supervised
      training in PST-PC and demonstrated satisfactory levels of fidelity and
      competency. Postintervention, we observed a 53% improvement in depressive
      symptoms (p < .001), a 23% improvement in HRQoL (p = .001), and an 18%
      improvement in participants' confidence to use problem-focused coping strategies
      (p = .001). CONCLUSIONS: Telephone-PST-PC delivered by a trained LVR practitioner
      may be an effective intervention for clients of LVR services who exhibit
      depressive symptoms. A randomized controlled trial is now needed to confirm these
      preliminary findings and establish longer-term effectiveness. (PsycINFO Database
      Record

PMID- 30113198
TI  - Psychosocial adjustment to a lower limb amputation ten months after surgery.
AB  - OBJECTIVE: This longitudinal multisite study examined the influence of
      demographic characteristics, psychological reactions, functionality, coping
      strategies, and social support on psychosocial adjustment to lower limb
      amputation 10 months after surgery. METHOD: Of an initial referral of 206
      Portuguese patients, a sample of 86 patients who underwent a lower limb
      amputation due to Diabetes Mellitus Type II were evaluated during the
      hospitalization that preceded surgery (t0) and at inpatient follow-up
      consultations, 1 (t1), 6 (t2), and 10 months (t3) after surgery. RESULTS: Higher
      levels of anxiety symptoms and functionality at presurgery were associated with
      lower social adjustment to amputation and with higher adjustment to the
      limitations (t3) respectively. Traumatic stress symptoms (t1) were negatively
      associated with general and social adjustment, and with the adjustment to the
      limitations (t3). Perceived social support (t2) mediated the relationship between
      traumatic stress symptoms (t1) and adjustment to the limitations (t3). Male
      gender was associated with a higher anxiety and depression symptoms (t0) and with
      a higher level of functionality (t1). Male gender was associated with
      functionality at presurgery and postsurgery, and with anxiety and depression
      symptoms of presurgery. IMPLICATIONS: Results support the need to improve
      psychological screening and early treatment of anxiety symptoms before the
      surgery, as well as depression and traumatic stress symptoms after a lower limb
      amputation, and the promotion of social support over time, in order to promote
      psychosocial adjustment to amputation. This set of psychosocial variables should
      be included when planning postamputation rehabilitation and psychosocial
      intervention programs for this target population. (PsycINFO Database Record

PMID- 30113199
TI  - Trajectories in postoperative recovery of elderly hip-fracture patients at risk
      for depression: A follow-up study.
AB  - OBJECTIVES: This secondary-analysis study aimed to identify distinct
      developmental depressive-symptom trajectories among elderly hip-fracture patients
      at risk for depression, examine the associations of trajectories with potential
      risk factors and care models, and explore the effect of trajectory membership on
      recovery outcomes. METHOD: Longitudinal data were obtained for 179 patients in a
      randomized controlled trial. These patients were included if their Geriatric
      Depression Scale short form scores were >= 5 before discharge or 1, 3, 6, or 12
      months following discharge. Individuals who followed similar developmental
      depressive-symptom trajectories were identified by group-based trajectory
      modeling. Associations between trajectory-group membership and postoperative
      outcomes over the 12 months following discharge were evaluated by the generalized
      estimating equations method. RESULTS: We identified a progressively lower-risk
      group and a fluctuating higher-risk group. Patients' membership in the
      progressively lower-risk group was associated with receiving a comprehensive care
      model featuring psychological and physical interventions. Membership in this
      group was associated with better postoperative outcomes and fewer emergency
      department visits or hospital readmissions. Patients were more likely to belong
      to the fluctuating higher-risk group if they had more comorbidities or worse
      prefracture mobility. Patients in the fluctuating higher-risk group not only had
      higher levels of depressive symptoms, but also a greater likelihood of poor
      postoperative recovery outcomes. CONCLUSIONS: Depressive symptoms in elderly hip
      fracture patients may be alleviated by postoperative comprehensive care that
      features both psychological and physical interventions. Patients with increasing
      depressive status should be targeted for early interventions. (PsycINFO Database
      Record

PMID- 30113200
TI  - Regaining equilibrium: Understanding the process of sibling adjustment to
      pediatric acquired brain injury.
AB  - OBJECTIVE: This study developed a comprehensive framework for understanding the
      process of sibling adjustment to pediatric acquired brain injury (ABI).
      PARTICIPANTS: Grounded theory methodology was employed to inductively explore the
      issues siblings perceived to be their main concerns and how they managed these
      concerns. Fifty-three interviews (N = 28) were conducted recursively with 20
      child and adolescent siblings of individuals with an ABI, 4 adult siblings of
      individuals with an ABI, and 4 child and adolescent siblings of individuals with
      congenital disability. Observational and secondary data from hospital staff and
      parents were also analyzed. The framework was developed and verified through
      simultaneous data collection and analysis that continued to the point of data
      saturation. RESULTS: The main concern for siblings was the loss of equilibrium in
      their lives as defined by the concepts of vulnerability and emotional turmoil.
      Losing equilibrium was enduring and threatened siblings' sense of security,
      safety, predictability and control many years post injury. To manage these
      concerns, siblings employed a variety of interrelated strategies to regain
      equilibrium. These strategies were conceptualized by the concepts navigating and
      sacrificing to restore safety, predictability, and control. Like the nonfinite
      nature of losing equilibrium, regaining equilibrium was an ongoing cyclical
      process. CONCLUSIONS: Rather than focusing on adjustment outcomes only, this
      study extends previous research by offering a framework for understanding the
      process of sibling adjustment, and thus providing a set of integrated categories,
      concepts, hypotheses, and propositions to inform future research and practice.
      (PsycINFO Database Record

PMID- 30113201
TI  - Rehabilitants' conscientiousness as a moderator of the intention-planning
      behavior chain.
AB  - PURPOSE/OBJECTIVE: After rehabilitation, it is important to maintain adopted
      target behaviors such as physical activity and physical exercise. By generating
      detailed behavioral plans, rehabilitants may translate their intentions into
      actual behavior. The aim of this study was to investigate whether
      Conscientiousness would further facilitate this mechanism in a way that
      rehabilitants who are more conscientious would be more likely to act upon their
      plans. Research Method/Design: The study presents secondary analyses from a
      larger intervention in cardiac and orthopedic rehabilitation. N = 136
      rehabilitants were surveyed via online questionnaires during treatment (Time 1
      [T1]) and with computer-assisted telephone interviews (CATIs) 6 weeks (Time 2
      [T2]) and 6 months (Time 3 [T3]) after discharge from the clinic. Intention,
      planning, Conscientiousness, and behavior were measured. A conditional process
      analysis examined whether Conscientiousness moderates the intention-planning
      physical activity chain. RESULTS: Planning had a mediating effect on intentions
      and physical activity. Moreover, this mediation effect was conditional on the
      level of Conscientiousness: Highly conscientious rehabilitants were more
      successful in translating their plans into behavior than their less conscientious
      counterparts. CONCLUSIONS/IMPLICATIONS: Self-regulatory mechanisms such as action
      facilitating planning strategies may be more efficient in conscientious
      rehabilitants. Conscientiousness reflects dispositional self-regulation and can
      be supportive when it comes to maintain difficult behaviors. Lack of
      Conscientiousness needs to be compensated by more intense support of
      rehabilitation patients, in order to plan appropriately and to act upon these
      plans in the face of barriers. (PsycINFO Database Record

PMID- 30113202
TI  - Subjective well-being differs with age in multiple sclerosis: A brief report.
AB  - OBJECTIVE: Increased age is associated with improved subjective well-being in the
      general population. However, there are conflicting findings regarding this
      association in individuals with multiple sclerosis (MS). In the present study, we
      examined differences in depression and quality of life (QOL) among 3 age groups
      of individuals with MS. METHOD: Participants consisted of 57 individuals with MS
      who were divided into 3 age groups: 35-44, 45-54, and 55-65 years. Outcome
      measures included the Mood and Evaluative scale t scores on the Chicago
      Multiscale Depression Inventory (CMDI) and the Physical and Mental scale scores
      on the Multiple Sclerosis Quality of Life Instrument (MSQOL-54). RESULTS: After
      controlling for disease duration, individuals in the oldest group reported
      significantly less severe depressive symptoms and better physical QOL than the
      youngest group. CONCLUSIONS: Results are consistent with theoretical predictions
      and observations of improved subjective well-being with age in the general
      population. Younger individuals with MS may be at higher risk for depression and
      poor QOL. Additional research is needed to model the findings in larger samples
      and clarify the theoretical mechanisms of the observed associations. (PsycINFO
      Database Record

PMID- 30113203
TI  - Cognitive Log performance among individuals without brain injury in an inpatient
      rehabilitation setting.
AB  - PURPOSE/OBJECTIVE: Despite the widespread use of the Cognitive Log, information
      regarding normative performance is only available in individuals with known brain
      injury and in healthy college students. The purpose of the current research is to
      provide information about Cognitive Log performance in a regional group of
      rehabilitation patients without history of brain injury. Secondarily, non
      neurological factors that may predict performance are considered. Research
      Method/Design: Participants included in this study were 121 consecutive patients
      admitted to an inpatient rehabilitation hospital spinal cord and orthopedic
      floor. Based on history, only patients without insult to the brain were included.
      RESULTS: This study provides normative information for Cognitive Log performance
      in a nonbrain injured population, showing that these patients score in between
      those with acquired brain injury and healthy controls. Variables including age,
      estimated intelligence, and self-reported pain, fatigue, and affective distress
      accounted for 47.5% of the variance in Cognitive Log scores, although age and
      estimated intelligence, which accounted for 43.3% of the variance, were the only
      individually significant contributors to performance. CONCLUSIONS/IMPLICATIONS:
      This study provides an estimate of normative Cognitive Log performance in a
      nonbrain injured population. This information is especially useful in that it
      signifies that both neurological and non-neurological factors contribute to
      Cognitive Log performance, and this information may shape how clinicians
      conceptualize scores in patients with and without brain injury. Age and
      longstanding intellectual abilities should be taken into consideration when
      interpreting Cognitive Log performances, developing rehabilitation strategies,
      and determining need for additional testing. (PsycINFO Database Record

PMID- 30113204
TI  - "The tolerance benefits of multicultural experiences depend on the perception of
      available mental resources": Correction to Tadmor et al. (2018).
AB  - Reports an error in "The tolerance benefits of multicultural experiences depend
      on the perception of available mental resources" by Carmit T. Tadmor, Ying-yi
      Hong, Melody M. Chao and Ayala Cohen (Journal of Personality and Social
      Psychology, Advanced Online Publication, Jul 23, 2018, np). In the article, the
      legend labels for Figure 4 are missing. The correct labels are Regulated-writing
      for the black bar and Free-writing for the gray bar. All versions of this article
      have been corrected. (The following abstract of the original article appeared in
      record 2018-34852-001.) Multicultural experience has been shown to lead to
      greater intergroup tolerance via reduced need for cognitive closure (NFCC).
      However, the requisite metacognitive conditions that facilitate this effect have
      yet to be examined. In 6 studies, we systematically demonstrated that the
      ameliorative effects of multicultural experience on intergroup bias are achieved
      only when individuals perceived that they had sufficient mental resources. Mental
      resources were either (a) measured during the Hong Kong "Umbrella Revolution"
      (Study 1), (b) experimentally manipulated in the lab through a classic depletion
      task (Study 2), or (c) subjectively recalled (Studies 3, 4, 5, and 6). We further
      showed that the moderating effects of perceived resource availability on the
      tolerance benefits of multicultural experience were mediated by reduced levels of
      NFCC (Studies 1, 5, and 6). This effect was consistent across a variety of
      targeted outgroups (Mainland Chinese, Arabs, Russians, Blacks, Asian Americans,
      and homosexuals), regardless of whether multicultural experience was measured or
      manipulated, and across samples (Hong Kongers, Jewish Israelis, and U.S.-born
      Americans). Overall, by integrating the literature on multicultural experiences
      with that on perceived resource depletion, we demonstrate the state-dependent
      nature of the advantages of multicultural experiences as well as afford a more
      nuanced view of the downstream influence of perceived mental depletion. (PsycINFO
      Database Record

PMID- 30113205
TI  - Introspection is not always blind to the costs of multitasking: The case of task
      switching.
AB  - Previous studies have provided evidence that introspection about dual-task
      performance in the psychological refractory period (PRP) paradigm is severely
      limited. The present study investigated introspection at the other pole of the
      multitasking continuum, namely task switching. In 2 experiments, participants
      provided estimates of their response times (i.e., introspective RTs) after each
      trial in modified versions of the alternating-runs and the task-cuing paradigm,
      which included only 2 tasks in a trial. In contrast to the previously observed
      unawareness of dual-task costs in the PRP paradigm, participants reported their
      switch costs in introspective RTs. Thus, introspection about multitasking
      performance appears to not always be as limited as in the PRP paradigm.
      Nevertheless, introspection is not without limits also in task switching.
      Participants only partly reported the beneficial impact of longer preparation
      time on their performance. The present results suggest that introspective RTs
      depend on multiple cues, of which some are valid and some are invalid. (PsycINFO
      Database Record

PMID- 30113206
TI  - The role of retrieval in answering multiple-choice questions.
AB  - Taking a test improves memory for that tested information, a finding referred to
      as the testing effect. Multiple-choice tests tend to produce smaller testing
      effects than do cued-recall tests, and this result is largely attributed to the
      different processing that the two formats are assumed to induce. Specifically, it
      is generally assumed that the multiple-choice format bypasses the need to
      retrieve information. Research suggests, however, that multiple-choice questions
      can be constructed to induce retrieval of information pertaining to the incorrect
      alternatives. In the present research, we investigated the processes that
      individuals use to answer multiple-choice questions and how those processes
      relate to later memory, particularly for information pertaining to the incorrect
      alternatives. Most critically, we found that participants sometimes spontaneously
      recall information pertaining to incorrect alternatives, and these spontaneous
      retrievals are associated with retention of those alternatives as correct answers
      to related questions later. Although multiple-choice questions can be constructed
      so as to bypass retrieval, they can also be constructed to induce retrieval, and
      when they are, learning benefits are likely to occur. The present work has
      practical implications for how instructors can create multiple-choice questions
      to induce processes that facilitate learning. (PsycINFO Database Record

PMID- 30113207
TI  - Representation and selection of determiners with phonological variants.
AB  - The aim of this study is to contribute to a better understanding of cross
      linguistic differences in the time course of determiner selection during language
      production. In Germanic languages, participants are slower at naming a picture
      using a determiner + noun utterance (die Katze "the cat") when a superimposed
      distractor is of a different gender (gender congruency effect). In Romance
      languages in which the pronunciation of the determiner also depends on the
      phonology of the next word, there is no such effect. This difference is
      traditionally assumed to arise because determiners are selected later in Romance
      languages (late selection hypothesis). It has further been suggested that in a
      given language, all determiners are either selected late or early (maximum
      consistency principle). Data on French have challenged these 2 hypotheses by
      revealing a gender congruency effect when participants name pictures using the
      definite singular determiner le-la (l' before vowels) and a noun, at positive
      stimulus onset asynchrony (SOA), that is, when there is a delay between the
      presentation of the picture and that of the distractor. We examined this finding
      further and investigated whether it generalizes to the indefinite determiner un
      une. Results of 4 picture-word interference experiments reveal that gender
      congruency effects in French are not restricted to the definite determiner or
      positive SOAs, but can be hard to detect in experiments which do not account for
      the variability in reading and naming times across participants and trials. We
      discuss the implications of these results for the modeling of determiner
      selection across languages. (PsycINFO Database Record

PMID- 30113208
TI  - Dissecting the role of Folr1 and Folh1 genes in the pathogenesis of metabolic
      syndrome in spontaneously hypertensive rats.
AB  - Increased levels of plasma cysteine predispose to obesity and metabolic
      disturbances. Our recent genetic analyses in spontaneously hypertensive rats
      (SHR) revealed mutated Folr1 (folate receptor 1) on chromosome 1 as a
      quantitative trait gene associated with reduced folate levels, hypercysteinemia
      and metabolic disturbances. The Folr1 gene is closely linked to the Folh1 (folate
      hydrolase 1) gene which codes for an enzyme involved in the hydrolysis of dietary
      polyglutamyl folates in the intestine. In the current study, we obtained evidence
      that Folh1 mRNA of the BN (Brown Norway) origin is weakly but significantly
      expressed in the small intestine. Next we analyzed the effects of the Folh1
      alleles on folate and sulfur amino acid levels and consecutively on glucose and
      lipid metabolism using SHR-1 congenic sublines harboring either Folr1 BN and
      Folh1 SHR alleles or Folr1 SHR and Folh1 BN alleles. Both congenic sublines when
      compared to SHR controls, exhibited significantly reduced folate clearance and
      lower plasma cysteine and homocysteine levels which was associated with
      significantly decreased serum glucose and insulin concentrations and reduced
      adiposity. These results strongly suggest that, in addition to Folr1, the Folh1
      gene also plays an important role in folate and sulfur amino acid levels and
      affects glucose and lipid metabolism in the rat.

PMID- 30113209
TI  - Oral Sensorimotor Intervention Enhances Breastfeeding Establishment in Preterm
      Infants.
AB  - OBJECTIVE: To assess the efficacy of an oral sensorimotor intervention on
      breastfeeding establishment and maintenance in preterm infants. STUDY DESIGN:
      Thirty-one preterm infants born <=34 weeks gestation were randomized into an
      experimental or control group. The experimental group received a 15-minute
      program consisting of stroking the peri-oral structures for the first 5 minutes,
      tongue exercises for the next 5 minutes, followed by non-nutritive sucking for
      the final 5 minutes. The control group received a sham intervention for the same
      duration. The interventions were administered once daily for 10 days. The
      outcomes included: time to attainment of full oral feeding, breastfeeding
      acquisition (i.e., >=50% of direct breastfeeding at hospital discharge),
      breastfeeding skill assessment using the Preterm Infant Breastfeeding Behavior
      Scale (PIBBS), length of hospitalization, and breastfeeding maintenance at 3 and
      6 months posthospitalization. RESULTS: Full oral feeding was attained earlier in
      the experimental group compared with the control (10.7 +/- 2.1 vs. 19.3 +/- 3.6
      days, p < 0.01). This was associated with a greater number of infants in the
      intervention group acquiring breastfeeding at hospital discharge compared with
      the controls (n = 11 vs. 5, p = 0.049). There was no statistical difference in
      PIBBS score, length of hospitalization, and breastfeeding rates at 3 and 6 months
      posthospitalization between the two groups (all tests, p > 0.32). CONCLUSIONS: An
      oral sensorimotor intervention accelerated the achievement of full oral feeding
      and enhanced direct breastfeeding rates at hospital discharge only. Provision of
      an oral sensorimotor intervention is a safe and low-cost intervention that may
      increase breastfeeding rates in a highly vulnerable population.

PMID- 30113210
TI  - Dietary supplementation with ferric tyrosine improves zootechnical performance
      and reduces caecal Campylobacter spp. load in broilers.
AB  - 1. The objective of this study was to evaluate the effect of ferric tyrosine on
      the reduction of Campylobacter spp. and zootechnical performance in broilers
      exposed to Campylobacter spp. using a natural challenge model to simulate
      commercial conditions. Additionally, the minimum inhibitory concentrations (MICs)
      of ferric tyrosine against common enteropathogens were evaluated. 2. At the start
      of the trial, 840 healthy male 1-d-old birds (Ross 308) were randomly allocated
      to 6 replicate pens of 35 birds each and fed diets containing different
      concentrations of ferric tyrosine (0, 0.02, 0.05 and 0.2 g/kg) in mash form for
      42 d. 3. Broilers fed diets containing ferric tyrosine showed significantly
      higher body weight at d 42 and weight gain compared to the control group.
      However, birds fed ferric tyrosine ate significantly more than the control birds
      so significant improvements in feed conversion rate were not observed. 4.
      Microbiological analyses of caecal samples collected on d 42 of the study showed,
      per gram of sample, 2-3 log10 reduction in Campylobacter spp. and 1 log10
      reduction in Escherichia coli in the groups fed diets containing ferric tyrosine
      compared to the control. 5. The MICs of ferric tyrosine was >400 mg/l for C.
      jejuni and >200 mg/l for E. coli and Salmonella enterica, indicating that ferric
      tyrosine did not exert antimicrobial activity. 6. The results showed that birds
      fed ferric tyrosine grew faster and consumed more feed compared to the control
      group, indicating potential benefits of faster time to reach slaughter weight
      with no significant reduction on feed efficiency. Moreover, ferric tyrosine
      significantly reduced caecal Campylobacter spp. and E. coli indicating potential
      as a non-antibiotic feed additive to lower the risk of infections transmitted
      through the food chain.

PMID- 30113211
TI  - Diabetes, subclinical atherosclerosis and multiple cardiovascular risk factors in
      hard-to-reach asymptomatic patients.
AB  - AIM:: To examine the association of cardiovascular disease risk factors with and
      their cumulative effect on coronary artery calcium in hard-to-reach asymptomatic
      patients with diabetes. METHODS:: A total of 2563 community-dwelling asymptomatic
      subjects from Central Appalachia participated in coronary artery calcium
      screening at a heart centre. Binary variable was used to indicate that coronary
      artery calcium was either present or absent. Independent variables consisted of
      demographic and modifiable risk factors and medical conditions. Descriptive
      statistics and multinomial logistic regression analyses were conducted. RESULTS::
      In total, 55.8% and 13.7% of study participants had subclinical atherosclerosis
      (coronary artery calcium ?1) and diabetes, respectively. The presence of coronary
      artery calcium was higher in subjects with diabetes (68.5%) than those without
      (53.8%). Compared to subjects without diabetes with coronary artery calcium = 0,
      obesity, hypertension, hypercholesterolaemia and smoking increased the odds of
      the presence of coronary artery calcium (coronary artery calcium score ?1)
      regardless of diabetes status; however, with larger odds ratios in subjects with
      diabetes. Compared to subjects without diabetes with coronary artery calcium
      score = 0, having 3, 4 and ?5 risk factors increased the odds of presence of
      coronary artery calcium in subjects with diabetes by 14.06 (confidence interval =
      3.26-62.69), 32.30 (confidence interval = 7.41-140.82) and 47.12 (confidence
      interval = 10.35-214.66) times, respectively. CONCLUSION:: There is a need for
      awareness about subclinical atherosclerosis in patients with diabetes and more
      research about coronary artery calcium in subpopulations of patients.

PMID- 30113212
TI  - Percutaneous Nephrolithotomy in Children: Analysis of Nationwide Hospitalizations
      and Short-Term Outcomes for the United States, 2001-2014.
AB  - OBJECTIVE: To describe population-wide utilization rates and outcomes of
      percutaneous nephrolithotomy (PCNL) in the management of pediatric upper urinary
      tract calculi (UUTC). PATIENTS AND METHODS: Patients <18 years with a diagnosis
      of UUTC, who underwent PCNL between 2001 and 2014 were identified from the
      National Inpatient Sample database. Annual PCNL rates, based on the at-risk
      population for each year, were estimated, and change in utilization rate was
      analyzed using negative binomial regression. Perioperative outcomes, hospital
      length of stay (LOS), and costs were determined; continuous and categorical
      variables were analyzed using nonparametric tests and Chi-squared tests,
      respectively. Trends tests and multivariable analyses (MVAs) were also performed
      where appropriate. RESULTS: An estimated 3206 pediatric PCNL procedures were
      performed. Mean annual PCNL rate increased significantly relative to 2001
      (incidence rate ratio = 1.40; 95% confidence interval 1.15-1.71, p = 0.001).
      Proportion of PCNL as a fraction of all inpatient surgical procedures for UUTC
      also significantly increased over time, from 15.7% in 2001 to 26.4% in 2014 (p <
      0.0001). Complications overall occurred in 20.7% of cases, with a significantly
      rising rate over time period (p < 0.0001). Complication rates were similar across
      hospital types and geographic regions. Median hospitalization cost was
      significantly higher for the West than for each of the other regions (p < 0.05 in
      each case). Median LOS was also highest for the West (4 days vs 3 days for each
      of the other regions). In MVA, significant predictors of both increased LOS and
      costs included black race, comorbidities of hypertension, diabetes, coagulopathy
      and neurologic disease, hospitalization in the South, and presence of
      complications. Race, gender, comorbidities, and treatment year were among the
      predictors of complications. CONCLUSIONS: PCNL utilization in the management of
      pediatric UUTC has significantly increased since 2001, with an associated
      increase in complication rates, although major complications were uncommon.
      Regional variations in costs and LOS were evident.

PMID- 30113213
TI  - SDH2 is involved in proper hypha formation and virulence in Candida albicans.
AB  - AIM: To investigate the role of SDH2 in Candida albicans filamentation and
      virulence. MATERIALS & METHODS: Caenorhabditis elegans and mouse candidiasis
      models were used to assess the virulence of a sdh2Delta/Delta mutant. Various
      hypha-inducing media were used to evaluate the hyphal development of C. albicans.
      DCFH-DA was used to measure intracellular Reactive Oxygen Species (ROS) levels.
      RESULTS: The sdh2Delta/Delta mutant was avirulent in the C. elegans model,
      hypovirulent in a murine candidiasis model, and defective to form filaments both
      in vitro and in vivo. Intracellular ROS level increased in the sdh2Delta/Delta
      mutant, and the filamentation defects of sdh2Delta/Delta were rescued by
      decreasing intracellular ROS. CONCLUSION: SDH2 plays an important role in C.
      albicans filamentation and virulence probably through affecting intracellular
      ROS. [Formula: see text].

PMID- 30113215
TI  - Waist Circumference and Subclinical Thyroid Dysfunction in a Large Cohort of
      Chinese Men and Women.
AB  - OBJECTIVE: The association between subclinical thyroid dysfunction and waist
      circumference (WC) is still controversial, especially from the perspective of sex
      differences. We aimed to explore the impact of sex on this relationship in a
      large Chinese cohort. METHODS: This cross-sectional study recruited 13,505
      healthy participants (8,346 males, 5,159 females) who were enrolled in a health
      check program. Clinical data were collected. The association between subclinical
      thyroid dysfunction and WC of both sexes was analyzed separately after dividing
      WC into quartiles. Odds ratios (ORs) were calculated by binary logistic
      regression models, and linear regression analysis was also performed. RESULTS:
      The prevalence rates of subclinical hyper-and hypothyroidism were significantly
      lower in males. Binary logistic regression models showed that WC in females with
      subclinical hypothyroidism had a detrimental effect with an OR of 1.011, but the
      effect disappeared when we included other covariates. The other ORs indicated no
      significant effects. The weak negative relationship between WC and thyrotropin
      was also indicated by linear regression analyses with very low R2 values.
      CONCLUSION: The current research did not show WC as a risk factor for subclinical
      thyroid dysfunction in either sex. Regional and ancestral origin differences may
      account for the variations with other studies. ABBREVIATIONS: ALT = alanine
      aminotransferase; BMI = body mass index; FT3 = free triiodothyronine; FT4 = free
      thyroxine; TG = triglycerides; TSH = thyroid-stimulating hormone; UA = uric acid;
      WC = waist circumference.

PMID- 30113214
TI  - Challenges in identifying antibiotic resistance targets for point-of-care
      diagnostics in general practice.
AB  - General practitioners stand at the front line of healthcare provision and have a
      pivotal role in the fight against increasing antibiotic resistance. In this
      respect, targeted antibiotic prescribing by general practitioners would help
      reduce the unnecessary use of antibiotics, leading to reduced treatment failures,
      fewer side-effects for patients and a reduction in the (global) spread of
      antibiotic resistances. Current 'gold standard' antibiotic resistance detection
      strategies tend to be slow, taking up to 48 h to obtain a result, although the
      implementation of point-of-care testing by general practitioners could help
      achieve the goal of targeted antibiotic prescribing practices. However, deciding
      on which antibiotic resistances to include in a point-of-care diagnostic is not a
      trivial task, as outlined in this publication.

PMID- 30113216
TI  - Pentamidine inhibits the growth of Sporothrix schenckii complex and exhibits
      synergism with antifungal agents.
AB  - AIM: The purpose of this study was to evaluate the effects of the
      antileishmanials meglumine antimoniate and pentamidine against Sporothrix
      schenckii complex. MATERIALS & METHODS: The antifungal activity of the two
      antileishmanials was assessed by broth microdilution. The interaction between the
      antileishmanials and antifungal drugs (amphotericin B, itraconazole and
      terbinafine) was evaluated by the checkerboard assay. The effect of prior
      exposure of Sporothrix spp. yeast cells to antileishmanials was evaluated by
      broth microdilution. RESULTS: Only pentamidine showed antifungal activity against
      Sporothrix spp. Synergistic interactions were observed between pentamidine and
      the antifungals. Also, the pre-exposure to meglumine antimoniate reduced the
      susceptibility of Sardinella brasiliensis and S. schenckii sensu stricto to
      amphotericin B and itraconazole. CONCLUSION: Pentamidine showed antifungal
      activity against Sporothrix spp., indicating it is a possible therapeutic
      alternative for the treatment of sporotrichosis.

PMID- 30113217
TI  - Identification of lncRNAs and Their Functional Network Associated with
      Chemoresistance in SW1990/GZ Pancreatic Cancer Cells by RNA Sequencing.
AB  - Drug resistance is a major problem in the treatment of pancreatic cancer (PC).
      Long noncoding (lnc)RNAs modulate a variety of cellular processes. This study was
      carried out to identify lncRNAs that are differentially expressed in drug
      resistant PC by next-generation RNA sequencing. We identified 205 differentially
      expressed lncRNAs (DELs) and 847 differentially expressed mRNAs (DEMs) in a
      comparison of gemcitabine-resistant and -sensitive SW1990 human PC cells. The
      expression levels of 12 randomly selected lncRNAs were confirmed by quantitative
      real-time PCR. A total of 55 and 99 DEMs were predicted to be targeted by the
      DELs through cis and trans mechanisms, respectively. The DEMs were significantly
      enriched in the Gene Ontology terms cell part, binding, and cellular processes,
      and a Kyoto Encyclopedia of Genes and Genomes analysis showed that they were
      associated with metabolic pathway, pathways in cancer, insulin resistance,
      microRNAs in cancer, and phosphotidylinositol 3-kinase-Akt signaling pathway. A
      coexpression network revealed a hub comprising lncRNAs (MIR210HG, SNHG1, and
      LOC729970) and mRNAs (RAB3D, DDX17, and SPNS2) that presumably mediate drug
      resistance in PC. The identified lncRNAs can serve as diagnostic or prognostic
      biomarkers and therapeutic targets for PC.

PMID- 30113218
TI  - Interactions of helminths with macrophages: therapeutic potential for
      inflammatory intestinal disease.
AB  - INTRODUCTION: Macrophages represent a highly heterogeneous and plastic cell type
      found in most tissues of the body; the intestine is home to enormous numbers of
      these cells. Considerable interest surrounds the 'M2 macrophage,' as it is able
      to control and regulate inflammation, while promoting tissue repair. Areas
      covered: As potent inducers of M2 macrophages, intestinal helminths and helminth
      derived products are ideal candidates for small molecule drug design to drive M2
      macrophage polarization. Several gastrointestinal helminths have been found to
      cause M2 macrophage-inducing infections. This review covers current knowledge of
      helminth products and their impact on macrophage polarization, which may in the
      future lead to new therapeutic strategies. A literature search was performed
      using the following search terms in PubMed: M2 macrophage, alternative
      activation, helminth products, helminth ES, helminth therapy, nanoparticle,
      intestinal macrophages. Other studies were selected by using references from
      articles identified through our original literature search. Expert commentary:
      While the immunomodulatory potential of helminth products is well established, we
      have yet to fully characterize many components of the intestinal helminth product
      library. Current work aims to identify the protein motifs responsible for
      modulation of macrophages and other components of the immune system.

PMID- 30113219
TI  - Pharmaceutical excipients properties and screw feeder performance in continuous
      processing lines: a Quality by Design (QbD) approach.
AB  - Screw feeder performance is a critical aspect in continuous manufacturing
      processes. Pharmaceutical excipients, such as mannitol, microcrystalline
      cellulose, lactose monohydrate, and anhydrous dibasic calcium phosphate can
      present problems in ensuring a continuous stable feed rate due to their sub
      optimal flow properties. In alignment with Quality by Design (QbD) goals, the aim
      of this work was to identify and explain critical sources of variability of some
      powder excipients delivery by screw feeding, in particular to continuous
      processing lines. Pharmaceutical excipients with a wide range of material
      properties were selected, and the impact of their flow and density properties on
      screw feeder performance was investigated. The analysis of the powder conveying
      by the screws was performed at different hopper fills and different screw speeds.
      A multivariable model involving bulk density (CBD) and parameters from FT4
      dynamic downwards testing (SI) and dynamic upwards testing (SE) explained 95.7%
      of excipients feed rates (p < .001). The study gathers valuable information about
      the screw feeder performance and input materials properties that can help process
      understanding and QbD-based development of solid dosage forms in continuous
      processing lines.

PMID- 30113221
TI  - Insights on the use of thermography in human physiology practical classes.

PMID- 30113220
TI  - Cardiac rhythm dance protocol: a smartphone-assisted, hands-on activity to
      introduce concepts of cardiovascular physiology and scientific methodology.
AB  - Physiology teaching resources have advanced to include innovative pedagogical
      approaches that meet the learning expectations of the current generation of
      students, while at the same time ensuring content delivery is accurate and the
      use of technologies is appropriate. We developed a quick experimental assay
      protocol to introduce the basic concepts of cardiac rhythms, and to demonstrate
      simultaneously that smartphone applications are a reliable and cost-effective
      tool for data collection in teaching the scientific method and performing
      physiology activities. The cardiac rhythm dance (CRD) protocol engages students
      in dancing a cardiac cyclelike movement to the rhythm of classical, pop, and
      samba music, and measuring their own cardiac frequency. Students collected their
      own data using the app Instant Heart Rate (Azumio). The CRD protocol allowed
      students to conclude that cardiac cycle-like movements paced by a pop song could
      represent the normal cardiac rhythm, whereas a classical song induced a
      significant reduction of heart rate, and the samba song significantly increased
      heart rate compared with the pop song. After group discussion, students
      considered that the pop rhythm is more realistic of day-by-day movement rhythms
      and is equivalent to the steady state of daily cardiac rhythms. Students
      considered the bradycardic and tachycardic movements to the dancing performed to
      the classical and samba rhythms, respectively. Thus the CRD protocol provides a
      multiple sensory-based and active learning resource that can engage students in
      learning cardiovascular physiology and recognizes smartphones as scientific
      instruments for collecting data during hands-on activities.

PMID- 30113222
TI  - Tackling the threshold concepts in physiology: what is the role of the laboratory
      class?
AB  - Laboratory practical programs are expected to fulfill many roles in the learning
      process, including the development of laboratory skills and problem-solving
      skills. However, little is known about the role of laboratory practical classes
      in the conceptual learning of physiology. Therefore, the main aims of this study
      were to identify some of the threshold concepts in physiology and to explore the
      role of our laboratory practical program in helping students to tackle these
      concepts. An online questionnaire gathered opinions from students on the value of
      the laboratory classes in helping them to learn. Interviews with students and
      with lecturers were performed to ascertain which concepts students find
      particularly difficult, why they find these concepts difficult, and what their
      opinions are on the role of the laboratory practical classes in helping students
      to grasp difficult concepts. A number of threshold concepts in physiology were
      identified, and some possible reasons underlying the difficulties were explored.
      Overall, the majority of respondents found that the laboratory practical program
      helped them to learn physiology. While the laboratory classes were found to
      promote conceptual learning in a number of ways, a prominent finding was that the
      laboratory classes help students to grasp the theory because they allow students
      to visually see the physiological events, they bring the theory to life, and they
      allow students to experience some applications of the theory. The study also
      highlighted areas for further development in relation to the promotion of
      conceptual learning within the teaching laboratory.

PMID- 30113224
TI  - Association Between Long Noncoding RNA MEG3 Polymorphisms and Lung Cancer
      Susceptibility in Chinese Northeast Population.
AB  - Long noncoding RNA (lncRNA) maternal-expressed gene 3 (MEG3) is associated with
      proliferation of various tumor cells and has decreased expression in many types
      of cancers. In this study, we aimed at demonstrating the association between MEG3
      polymorphisms and the risk of lung cancer in northeast China. There were 526 lung
      cancer patients and 526 healthy controls included in this hospital-based case
      control study. The genotyping of two polymorphisms, rs7158663 G > A and rs4081134
      G>A, was performed by the Taqman allelic discrimination method. We found that
      MEG3 rs4081134-AA may be associated with the risk of lung cancer (AA vs. GG:
      adjusted odds ratio [OR] = 0.487, confidence interval [95% CI] = 0.257-0.897, p =
      0.030; AA vs. AG+GG: adjusted OR = 0.522, 95% CI = 0.274-0.992, p = 0.047).
      Similar associations in several subgroups were found in subsequent stratified
      analysis. Further, there were no statistically significant interactions of
      rs4081134 polymorphism and smoking to lung cancer susceptibility. In addition,
      the associations between the MEG3 rs7158663 polymorphism and lung cancer
      susceptibility were not found. These results indicate that the MEG3 rs4081134
      polymorphism was significantly associated with lung cancer susceptibility in the
      Chinese population.

PMID- 30113225
TI  - Host Genetic Polymorphisms Influencing Susceptibility to Dengue.
AB  - Dengue is a pandemic-prone viral disease which is endemic in more than 100
      countries and which puts half of the world's population at risk. While the
      disease presents as subclinical infection or mild fever in the majority of cases,
      approximately a quarter of the infected individuals experience severe forms of
      disease like dengue hemorrhagic fever/dengue shock syndrome that cause
      significant rates of mortality and morbidity. The pathogenesis of this
      differential outcome of infection is determined by a complex interplay of factors
      associated with the virus, vector, and host; much of which is not completely
      understood. In this review, we present an update on the various host genetic
      polymorphisms that have been reported to influence the susceptibility to dengue.
      For the convenience of discussion, we have categorized the genetic factors
      according to the different arms of the immune system with which the corresponding
      immune determinants are associated.

PMID- 30113226
TI  - Antibiotic Utilization Before Endourological Surgery for Urolithiasis:
      Endourological Society Survey Results.
AB  - INTRODUCTION: Ureteroscopy (URS) and percutaneous nephrolithotomy (PCNL) are
      common procedures performed to treat kidney stones. Despite advances in
      technology/technique, serious infectious complications can occur. To better
      understand the preoperative antibiotic administration patterns and adherence to
      guidelines from the American Urological Association (AUA) and the European
      Association of Urology (EAU), members of the Endourological Society were sent a
      clinical vignette-based survey to assess the antibiotic use in a variety of pre
      URS and pre-PCNL scenarios. METHODS: Endourological Society members were e-mailed
      a survey that queried antibiotic therapy duration before uncomplicated URS and
      PCNL with negative and asymptomatic positive preoperative urine cultures (PUCs).
      For negative PUC questions, selecting more perioperative antibiotics was
      considered a "prolonged" course as it extends past the maximum of 24-hour
      perioperative prophylaxis recommended by both the AUA and EAU. RESULTS: The
      response rate was 16.3% for a total of 326 responders. Twenty-one percent to 39%
      of respondents reported giving prolonged courses of preoperative antibiotics
      before a URS or PCNL with a negative PUC (p < 0.0001). When presented with a
      negative PUC, more prolonged antibiotic courses were reported with the following
      hierarchy: PCNL for 2 cm intrarenal stones (39%) > URS for 12 mm renal pelvis
      stone (28%) > URS for 7 mm distal ureteral stones (21%) (p < 0.0001). In both
      negative and positive PUC questions, differences were noted in preoperative
      antibiotic prescribing patterns among site of practice (United States, Canada,
      Europe, Asia, South America, and Others), type of practice (academic vs all
      others), years in practice (<10 or >=10 years), and surgical volume (URS and PCNL
      >100 or <=100 annual cases). CONCLUSIONS: Adherence to guidelines on antibiotic
      administration before PCNL and URS with a negative PUC varies by scenario and
      provider. In 21% to 39% of negative PUC cases, reported antibiotic use before a
      URS or PCNL is not consistent with recommendations from the AUA and EAU. Before a
      positive PUC URS or PCNL, nearly all surveyed provide preoperative antibiotics;
      however, the regimen length is variable.

PMID- 30113223
TI  - Responding to the emergence of antifungal drug resistance: perspectives from the
      bench and the bedside.
AB  - The incidence of serious fungal infections is increasing rapidly, and yet the
      rate of new drugs becoming available to treat them is slow. The limited
      therapeutic armamentarium is a challenge for clinicians, because the available
      drugs are often toxic, expensive, difficult to administer, ineffective or a
      combination of all four. Given this setting, the emergence of resistance is
      especially concerning, and a review of the topic is timely. Here we discuss
      antifungal drug resistance in Candida spp. and Aspergillus spp. with reference to
      the most commonly used first-line antifungal agents - azoles and echinocandins.
      We review the resistance mechanisms of the leading pathogens, how resistance can
      be identified in the diagnostic lab and the clinical implications of resistance
      once detected.

PMID- 30113227
TI  - Early Airway Microbial Metagenomic and Metabolomic Signatures are Associated with
      Development of Severe Bronchopulmonary Dysplasia.
AB  - The pathogenesis of bronchopulmonary dysplasia (BPD) is not well understood. We
      previously identified differences in the airway microbiome at birth between
      preterm infants who were BPD-predisposed versus those who were BPD-resistant. In
      this study, we attempted to identify mechanisms by which the airway microbiome
      could modify the risk for BPD. We used a software-based method to predict the
      metagenome of the tracheal aspirate (TA) microbiome from 16s rRNA sequencing data
      in preterm infants and to identify functional ortholog genes that were
      differentially abundant in BPD-predisposed and BPD-resistant infants. We also
      identified metabolites that were differentially enriched in these samples using
      untargeted mass spectrometry and mummichog to identify the metabolic pathways
      involved. Microbial metagenome analysis identified specific pathways that were
      less abundant in the functional metagenome of the microbiota of BPD-predisposed
      infants compared to BPD-resistant infants. The airway metabolome of BPD
      predisposed infants was enriched for metabolites involved in fatty acid
      activation, androgen and estrogen biosynthesis compared to BPD-resistant infants.
      These findings suggest that in extremely preterm infants, the early airway
      microbiome may alter the metabolome thereby modifying the risk of BPD. The
      differential enrichment of sex steroid metabolic pathways support previous
      studies suggesting a role for sexual dimorphism in BPD risk. This study also
      suggests a role for metabolomic and metagenomic profiles to serve as early
      biomarkers of BPD risk.

PMID- 30113228
TI  - Ancestry and Genetic Associations with Bronchopulmonary Dysplasia in Preterm
      Infants.
AB  - Bronchopulmonary dysplasia in premature infants is a common and often severe lung
      disease with long term sequelae. A genetic component is suspected but not fully
      defined. We performed an ancestry and genome-wide association study to identify
      variants, genes and pathways associated with survival without bronchopulmonary
      dysplasia in 387 high-risk infants treated with inhaled nitric oxide in the Trial
      of Late Surfactant study. Global African genetic ancestry was associated with
      increased survival without bronchopulmonary dysplasia among infants of maternal
      self-reported Hispanic White race/ethnicity (OR=4.5, p=0.01). Admixture mapping
      found suggestive outcome associations with local African ancestry at 18q21 and
      10q22 among infants of maternal self-reported African American race/ethnicity.
      For all infants, the top individual variant identified was within the intron of
      NBL1, which is expressed in mid-trimester lung and is an antagonist of bone
      morphogenetic proteins (rs372271081, OR=0.17, p=7.4x10-7). The protective allele
      of this variant was significantly associated with lower nitric oxide metabolites
      in the urine of non-Hispanic white infants (p= 0.006), supporting a role in the
      racial differential response to nitric oxide. Interrogating genes upregulated in
      bronchopulmonary dysplasia lungs indicated association with variants in CCL18, a
      cytokine associated with fibrosis and interstitial lung disease, and pathway
      analyses implicated variation in genes involved in immune/inflammatory processes
      in response to infection and mechanical ventilation. Our results suggest that
      genetic variation related to lung development, drug metabolism, and immune
      response contribute to individual and racial/ethnic differences in respiratory
      outcomes following inhaled nitric oxide treatment of high-risk premature infants.

PMID- 30113229
TI  - Umbilical Cord Blood Metabolomics Reveal Distinct Signatures of Dyslipidemia
      Prior to Bronchopulmonary Dysplasia and Pulmonary Hypertension.
AB  - Pulmonary hypertension (PH) is a common consequence of bronchopulmonary dysplasia
      (BPD) and remains a primary contributor to increased morbidity and mortality
      among preterm infants. Unfortunately, at the present time there are no reliable
      early predictive markers for BPD-associated PH. Considering its health
      consequences, understanding in utero perturbations that lead to the development
      of BPD and BPD-associated PH and identifying early predictive markers is of
      utmost importance. As part of the discovery phase, we applied a multi-platform
      metabolomics approach consisting of untargeted and targeted methodologies to
      screen for metabolic perturbations in umbilical cord blood (UCB) plasma from
      preterm infants that did (n=21; cases) or did not (n=21; controls) develop
      subsequent PH. A total of 1,656 features were detected of which 407 were
      annotated by metabolite structures. PH-associated metabolic perturbations were
      characterized by reductions in major choline-containing phospholipids such as
      phosphatidycholines (PCs) and sphingomyelins, indicating altered lipid
      metabolism. The reduction in UCB abundances of major choline-containing
      phospholipids was confirmed in an independent validation cohort consisting of UCB
      plasmas from 10 cases and 10 controls matched for gestational age and BPD status.
      Sub-analyses in the discovery cohort indicated that elevations in the oxylipins
      PGE1, PGE2, PGF2a, 9- and 13-HOTE, 9- and 13-HODE, and 9- and 13-KODE were
      positively associated with BPD presence and severity. This expansive evaluation
      of cord blood plasma identifies compounds reflecting dyslipidemia and suggest
      altered metabolite provision associated with metabolic immaturity that
      differentiate subjects both by BPD severity and PH development.

PMID- 30113230
TI  - What pharmacotherapeutics should one use for early stage non-small cell lung
      cancer?

PMID- 30113231
TI  - Low-Molecular-Weight Heparin for the Prevention of Venous Thromboembolism in
      Patients Undergoing Knee Arthroscopic Surgery and Anterior Cruciate Ligament
      Reconstruction: A Meta-analysis of Randomized Controlled Trials.
AB  - BACKGROUND: Low-molecular-weight heparin (LMWH) thromboprophylaxis is widely used
      for reducing the risk of thrombosis after major orthopaedic surgery. However, the
      effect and safety on knee arthroscopic surgery are still controversial. PURPOSE:
      To assess the efficacy and safety of LMWH for the prevention of symptomatic
      venous thromboembolism (VTE) after knee arthroscopic surgery and anterior
      cruciate ligament reconstruction (ACLR) by conducting a meta-analysis of
      randomized controlled trials (RCTs). STUDY DESIGN: Meta-analysis. METHODS: The
      authors searched the electronic databases of MEDLINE, Embase, Cochrane Central
      Register of Controlled Trials (CENTRAL), ClinicalTrials.gov , and Web of Science
      for all studies from inception to June 30, 2017. All selected studies were
      categorized into 2 subgroups: simple knee arthroscopic surgery and ACLR. The
      primary effect and safety endpoint were the incidence of major VTE and major
      bleeding events (BEs), respectively. The secondary effect and safety endpoint
      were the incidence of all VTE and all BEs, respectively. Relative risks (RRs)
      with 95% CIs were calculated using Review Manager 5.3. RESULTS: Eight RCTs with
      4113 patients were included. For patients undergoing simple knee arthroscopic
      surgery, LMWH prophylaxis did not bring a significant reduction in the risk of
      major VTE (RR, 1.00 [95% CI, 0.37-2.67]; P > .99) and all VTE (RR, 0.63 [95% CI,
      0.31-1.29]; P = .21) and did not increase the risk of major BEs (RR, 0.98 [95%
      CI, 0.06-15.72]; P = .99) but did have a higher risk of all BEs (RR, 1.64 [95%
      CI, 1.18-2.28]; P = .003) in comparison with non-LMWH prophylaxis. For patients
      undergoing ACLR, LMWH prophylaxis was associated with a significantly lower rate
      of major VTE (RR, 0.23 [95% CI, 0.12-0.43]; P < .001) and all VTE (RR, 0.22 [95%
      CI, 0.06-0.73]; P = .01) but no increase in major BEs (RR, 1.80 [95% CI, 0.19
      17.25]; P = .61) and all BEs (RR, 1.12 [95% CI, 0.72-1.74]; P = .61) in
      comparison with non-LMWH prophylaxis. CONCLUSION: Compared with non-LMWH
      treatment, LMWH had no significant efficacy in preventing VTE in patients
      undergoing simple knee arthroscopic surgery but increased the risk of BEs.
      However, LMWH had significant efficacy in preventing VTE for patients mainly
      undergoing ACLR and did not increase the risk of BEs.

PMID- 30113232
TI  - Hereditary cancer testing challenges: assembling the analytical pieces to solve
      the patient clinical puzzle.
AB  - Expanded genetic test utilization to guide cancer management has driven the
      development of larger gene panels and greater diversity in the patient population
      pursuing testing, resulting in increased identification of atypical or
      technically challenging genetic findings. To ensure appropriate patient care, it
      is critical that genetic tests adequately identify and characterize these
      findings. We describe genetic testing challenges frequently encountered by our
      laboratory and the methodologies we employ to improve test accuracy for the
      identification and characterization of atypical genetic findings. While these
      findings may be individually rare, 15,745 (9%) individuals tested by our
      laboratory for hereditary cancer risk had an atypical genetic finding,
      highlighting the importance of employing highly accurate and comprehensive
      methods in clinical genetic testing.

PMID- 30113233
TI  - Selecting appropriate weight loss pharmacotherapies in older adults to reduce
      cardiovascular risk.

PMID- 30113234
TI  - Leveling the playing field: can psychological coping resources reduce the
      influence of physical and technical skills on athletic performance?
AB  - BACKGROUND AND OBJECTIVES: The present study assessed the extent to which
      individual differences in psychological coping resources are related to athletic
      performance; whether they can attenuate the amount of performance variance
      accounted for by physical/technical skills; and whether coping resources remain
      significant predictors of performance when physical/technical skill level is
      statistically controlled. METHODS: Twenty college golf coaches rated the
      physical/technical skills of 189 men and women varsity golfers on their teams.
      Athletes completed the Athletic Coping Skills Inventory (ACSI-28), with the total
      (Personal Coping Resources) score serving as a global measure of sport-relevant
      psychological coping resources. Subsequent performance (stroke average per round)
      of 105 golfers was assessed over a mean of 12.04 competitive rounds during the
      remainder of the season. RESULTS: Physical/technical skills and psychological
      coping resource measures were minimally correlated and both were significant and
      similarly influential predictors of performance. With psychological resources
      controlled, performance variance accounted for by physical/technical skills was
      reduced from 21.2% to 10.6%. With physical/technical skills statistically
      controlled, psychological coping resources, though reduced from 18.2% to 7.5% of
      accountable variance, remained a significant predictor of performance.
      CONCLUSION: Results support the significant role played by psychological coping
      resources as predictors of athletic performance, together with their ability to
      "level the field" by reducing the influence of physical/technical talent.

PMID- 30113235
TI  - Scavenger receptor class BI (SR-BI) mediates uptake of CPX-351 into K562 leukemia
      cells.
AB  - PURPOSE: CPX-351 is a liposomal formulation of cytarabine and daunorubicin
      encapsulated at a 5:1 molar ratio, for the treatment of acute myeloid leukemia.
      The Scavenger Receptor class B type I (SR-BI) plays an important role in
      mediating the uptake of high-density lipoproteins. The purpose of this study is
      to assess the role of the cell surface lipoprotein receptor SR-BI in the uptake
      of CPX-351 liposomes (Jazz Pharmaceuticals) into K562 leukemia cells. METHODS:
      K562 cells were pre-treated with 10 nM siRNA for 48 h and then treated with
      varying amount of CPX-351 for 24, 48 and 72 h. Cells were then collected and
      analyzed at 480/590 nm on a CytoFLEX Multicolour flow instrument to determine
      cellular uptake of daunorubicin. Experimental data were analyzed using two-way
      ANOVA with Bonferroni multiple comparisons. Significance was set at p < .05.
      RESULTS: K562 cells pre-treated with SR-BI siRNA for 48 h had a reduced SRB1 cell
      surface concentration (74-85%). Addition of CPX-351 at 10-50 nM followed by
      measurement of cellular daunorubicin at 48, 48 or 72 h showed a significantly
      lower percentage of daunorubicin positive population compared with control K562
      cells (p < .05). There was significantly less daunorubicin taken up in the SR-BI
      knock-down cells across all drug concentrations and at all three time points,
      although there were no concentration-related trends. CONCLUSIONS: These
      preliminary studies suggest that SR-BI may be one potential mechanism by which
      CPX-351 is taken up into K562 cells.

PMID- 30113236
TI  - Acid suppressant medications and the risk of allergic diseases.
AB  - INTRODUCTION: Acid suppressant medications (ASMs), such as proton pump inhibitors
      and histamine-2 receptor antagonists, are used often and throughout the lifespan.
      These medications have been linked to the development of a variety of allergic
      diseases. Areas covered: This review discusses prior studies investigating the
      association between acid ASM exposure and the development of allergic diseases.
      We performed a thorough literature search to identify potentially relevant
      studies for inclusion. In summary, exposure to these medications prenatally, in
      childhood and in adulthood, may increase the risk of allergic diseases. The
      current evidence is limited by primarily observational study design and potential
      bias and confounding. The mechanism of action is not yet known, but there are
      several proposed theories. Expert commentary: There is a growing body of evidence
      to support that exposure to acid ASMs increases the risk of developing allergic
      diseases. Further research is needed to not only clarify this relationship but to
      define the potential mechanism of action. If further research confirms these
      observations, we believe that could warrant changes in the patterns of
      prescribing and use of acid ASMs.

PMID- 30113237
TI  - Do antimicrobial peptides and antimicrobial-peptide resistance play important
      roles during bacterial infection?

PMID- 30113238
TI  - A cost-effectiveness modeling evaluation comparing a biosimilar follitropin alfa
      preparation with its reference product for live birth outcome in Germany, Italy
      and Spain.
AB  - BACKGROUND/OBJECTIVE: Although biosimilar drugs may be cheaper to purchase than
      reference biological products, they may not be the most cost-effective treatment
      to achieve a desired outcome. The analysis reported here compared the overall
      costs to achieve live birth using the reference follitropin alfa (GONAL-f) or a
      biosimilar (Ovaleap) in Spain, Italy and Germany. METHODS: Patient and treatment
      data was obtained from published sources; assisted-reproductive technology,
      gonadotropin, follow-up and adverse-event-related costs were calculated from
      tariffs and reimbursement frameworks for each country. Incremental cost
      effectiveness ratios (ICERs) were calculated from the difference in costs between
      reference and biosimilar in each country, divided by the difference in live-birth
      rates. Mean cost per live birth was calculated as total costs divided by the live
      birth rate. RESULTS: The published live birth rates were 32.2% (reference) and
      26.8% (biosimilar). Drug costs per patient were higher for the reference
      recombinant human follicle-stimulating hormone in all three countries, with
      larger cost differences in Germany (?157.38) and Italy (?141.50) than in Spain
      (?22.41). The ICER for the reference product compared with the biosimilar was
      ?2917.47 in Germany, ?415.43 in Spain and ?2623.09 in Italy. However, the overall
      cost per live birth was higher for the biosimilar in all three countries (Germany
      ?8135.04 vs. ?9185.34; Italy ?8545.22 vs. ?9733.37; Spain ?14,859.53 vs.
      ?17,767.19). Uncertainty in efficacy, mean gonadotropin dose and costs did not
      have a strong effect on the ICERs. CONCLUSIONS: When considering live birth
      outcomes, treatment with the reference follitropin alfa was more cost effective
      than treatment with the biosimilar follitropin alfa.

PMID- 30113239
TI  - Factors that drive the increasing use of FFPE tissue in basic and translational
      cancer research.
AB  - The decision to use 10% neutral buffered formalin fixed, paraffin embedded (FFPE)
      archival pathology material may be dictated by the cancer research question or
      analytical technique, or may be governed by national ethical, legal and social
      implications (ELSI), biobank, and sample availability and access policy.
      Biobanked samples of common tumors are likely to be available, but not all
      samples will be annotated with treatment and outcomes data and this may limit
      their application. Tumors that are rare or very small exist mostly in FFPE
      pathology archives. Pathology departments worldwide contain millions of FFPE
      archival samples, but there are challenges to availability. Pathology departments
      lack resources for retrieving materials for research or for having pathologists
      select precise areas in paraffin blocks, a critical quality control step. When
      samples must be sourced from several pathology departments, different fixation
      and tissue processing approaches create variability in quality. Researchers must
      decide what sample quality and quality tolerance fit their specific purpose and
      whether sample enrichment is required. Recent publications report variable
      success with techniques modified to examine all common species of molecular
      targets in FFPE samples. Rigorous quality management may be particularly
      important in sample preparation for next generation sequencing and for optimizing
      the quality of extracted proteins for proteomics studies. Unpredictable failures,
      including unpublished ones, likely are related to pre-analytical factors,
      unstable molecular targets, biological and clinical sampling factors associated
      with specific tissue types or suboptimal quality management of pathology
      archives. Reproducible results depend on adherence to pre-analytical phase
      standards for molecular in vitro diagnostic analyses for DNA, RNA and in
      particular, extracted proteins. With continuing adaptations of techniques for
      application to FFPE, the potential to acquire much larger numbers of FFPE samples
      and the greater convenience of using FFPE in assays for precision medicine, the
      choice of material in the future will become increasingly biased toward FFPE
      samples from pathology archives. Recognition that FFPE samples may harbor greater
      variation in quality than frozen samples for several reasons, including
      variations in fixation and tissue processing, requires that FFPE results be
      validated provided a cohort of frozen tissue samples is available.

PMID- 30113240
TI  - The olfactory mucosa: a potential source of stem cells for hearing regeneration.
AB  - The olfactory mucosa contains cells that enable it to generate new neurons and
      other supporting cells throughout life, allowing it to replace cells of the
      mucosa that have been damaged by exposure to various insults. In this article, we
      discuss the different types of stem cell found within the olfactory mucosa and
      their properties. In particular, the mesenchymal-like cells found within the
      lamina propria will be reviewed in detail. In addition, we discuss potential
      applications of olfactory-derived stem cells toward hearing regeneration
      secondary to either inner hair cell loss or primary or secondary auditory nerve
      degeneration.

PMID- 30113241
TI  - Utility of international normative 20 m shuttle run values for identifying youth
      at increased cardiometabolic risk.
AB  - The purpose of this study was to examine the ability of international normative
      centiles for the 20 m shuttle run test (20mSRT) to identify youth at increased
      cardiometabolic risk. This was a cross-sectional study involving 961 children
      aged 10-17 years (53% girls) from the United Kingdom. Receiver operating
      characteristic (ROC) curves determined the discriminatory ability of
      cardiorespiratory fitness percentiles for predicting increased cardiometabolic
      risk. ROC analysis demonstrated a significant but poor discriminatory accuracy of
      cardiorespiratory fitness in identifying low/high cardiometabolic risk in girls
      (AUC = 0.58, 95% CI: 0.54-0.63; p = 0.04), and in boys (AUC = 0.59, 95% CI: 0.54
      0.63; p = 0.03). The cardiorespiratory fitness cut-off associated with high
      cardiometabolic risk was the 55th percentile (sensitivity = 33.3%; specificity =
      84.5%) in girls and the 60th percentile (sensitivity = 42.9%; specificity =
      73.6%) in boys. These 20mSRT percentile thresholds can be used to identify
      children and adolescents who may benefit from lifestyle intervention.
      Nonetheless, further work involving different populations and cardiometabolic
      risk scores comprising of different variables are needed to confirm our initial
      findings.

PMID- 30113242
TI  - Introducing a new standardized nanomaterial environmental toxicity screening
      testing procedure, ISO/TS 20787: aquatic toxicity assessment of manufactured
      nanomaterials in saltwater Lakes using Artemia sp. nauplii.
AB  - This paper introduces a new standardized testing procedure for nanomaterial
      environmental toxicity (International Organization for Standardization/Technical
      Specification (ISO/TS) 20787): 'aquatic toxicity assessment of manufactured
      nanomaterials in saltwater lakes using Artemia sp. Nauplii' intended to generate
      more reliable and repeatable aquatic toxicity data testing manufactured
      nanomaterials, using Artemia sp., to evaluate their possible ecotoxicity in
      saltwater lake ecosystems. The principles behind testing with Artemia sp. are
      reviewed and the paper gives an overview of research published between 2009 and
      2018 in which manufactured nanomaterials were tested using Artemia sp.

PMID- 30113243
TI  - Systemic and Cerebral Hemodynamic Contribution to Cognitive Performance in Spinal
      Cord Injury.
AB  - Cognitive deficits are prevalent in the spinal cord injury (SCI) population, and
      consensus suggests that concomitant traumatic brain injury or comorbid conditions
      are primarily responsible for these deficits. However, mounting evidence supports
      the possibility that systemic and cerebral hemodynamic dysfunction may contribute
      to the cognitive deficits reported in persons with SCI. We sought to determine
      the contribution of changes in blood pressure (BP) and changes in cerebral blood
      flow velocity (CBFv) to test performance on the Symbol Digit Modalities Test
      (SDMT) in persons with SCI compared with matched non-SCI controls. Participants
      included 36 non-SCI controls and 67 persons with SCI: 33 with paraplegia (T2-T12)
      and 34 with tetraplegia (C3-T1). Continuous beat-to-beat BP and simultaneous CBFv
      was monitored for 5 min during seated rest and during the SDMT, which assesses
      information processing speed, sustained attention, and visual working memory. The
      results indicate significantly lower SDMT scores in the group with tetraplegia
      (44 +/- 10) compared to the non-SCI controls (53 +/- 14; p < 0.01); however, SDMT
      scores did not differ significantly between the non-SCI controls and the group
      with paraplegia (49 +/- 13). Whereas group affiliation was the most significant
      predictor of test performance (F = 4.84; p = 0.010, eta2 = 0.088), change in
      systolic BP (SBP) (r2 = 0.047, p = 0.028) and change in diastolic CBFv (DFV) (r2
      = 0.047, p = 0.028) contributed significantly to SDMT scores. Further, change in
      SBP accounted for a significant amount of variance in change in DFV in the total
      study sample (r2 = 0.090; p = 0.002). These results support previous findings of
      cognitive deficits in persons with SCI and indicate that inadequate systemic and
      cerebral hemodynamic responses to testing contribute to test performance.
      Therefore, clinical treatment of cognitive dysfunction in the SCI population
      should consider focusing on increasing systemic BP to improve CBFv, particularly
      in individuals with lesions above T1.

PMID- 30113245
TI  - A nationwide epidemiological study on the prevalence of multiple sclerosis and
      neuromyelitis optica spectrum disorder with important multi-ethnic differences in
      Malaysia.
AB  - OBJECTIVES: This study looked at observed crude prevalence/incidence of multiple
      sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) in Malaysia and
      identified any inter-ethnic differences for MS/NMOSD. METHODS: This was a
      nationwide tertiary hospital-based retrospective cross-sectional study using the
      capture-recapture method. It looked at the estimated crude prevalence of
      confirmed MS and NMOSD and annual incidence on 29 December 2017. Recapture of
      data was done between February and March 2018 on 1 March 2018. Public and
      referring private institutions were accessed. RESULTS: The survey identified 767
      MS and 545 NMOSD subjects, with crude prevalence rates of 2.73 per 100,000 (95%
      confidence interval (CI): 2.53; 2.92 per 100,000 population) and 1.94 per 100,000
      (95% CI: 1.77; 2.10 per 100,000 population) with observed crude annual incidence
      of 0.55 (95% CI: 0.43; 0.58) for MS and 0.39 per 100,000 (95% CI: 0.35; 0.47) for
      NMOSD. The MS:NMOSD ratios were 1.4:1.0. The capture-recapture method revealed
      913 MS (95% CI: 910; 915.9) and 580 (95% CI: 578.8; 581.2) NMOSD with prevalence
      per 100,000 of 3.26 (95% CI: 3.05; 3.47) and 2.07 (95% CI: 1.90; 2.24),
      respectively. In the MS group, 59.4% were Malay, 16.6% Chinese, 20.5% Indian, and
      3.5% were from indigenous groups. In the NMOSD group, 47.3% were Malay, 46.9%
      Chinese, 3.5% Indian, and 2.3% were from other indigenous groups. The ratio of
      NMOSD to MS among the Chinese was 2:1, but the ratio of MS to NMOSD among the
      Malays was 1.8:1, and that in Indians was 8.3:1. CONCLUSION: There is a modest
      increase in the prevalence of MS and NMOSD in Malaysia with inter-ethnic
      differences for MS/NMOSD.

PMID- 30113244
TI  - Pain Outcomes After Celiac Plexus Block in Children and Young Adults with Cancer.
AB  - PURPOSE: The use of celiac plexus block (CPB) for abdominal pain has been
      extensively reported in adults. However, pediatric literature is limited to three
      single case reports and a series of three cases. This study evaluated the
      effectiveness of CPB in children and young adults (aged 8-20 years) with
      abdominal malignancies. METHODS: Pain outcomes after CPB were evaluated in four
      children and young adults with cancer. Mean daily pain score (PS, 0-10) and
      morphine consumption (intravenous morphine equivalent daily [MED], mg/kg/day)
      before and after CPB were used to assess effectiveness. RESULTS: Mean daily PS
      reduced after CPB in all patients. In one patient, this reduction was sustained
      up to 6 months of follow-up, and analgesics were discontinued 1 week after CPB.
      The other three patients had limited survival (6, 16, and 37 days) after CPB. One
      patient had a PS of 0 over the last few days of life, but the MED was escalated
      from 0.74 before the block to 5.4 mg/kg/day at the end of life. In the other two
      patients, MED was lower during the first week after CPB than that before CPB
      (4.55 vs. 1.59 and 2.88 vs. 1.51 mg/kg/day, respectively). As these two patients
      had disease progression during their last days of life, the MED was increased to
      4.75 and 263.9 mg/kg/day, respectively. CONCLUSIONS: Our results suggest that CPB
      may contribute to reducing PS and MED. We observed the use of CPB rather late in
      the disease trajectory.

PMID- 30113246
TI  - How do expatriate health workers cope with needs to provide palliative care in
      humanitarian emergency assistance? A qualitative study with in-depth interviews.
AB  - BACKGROUND:: Given the worldwide increase of chronic diseases, expatriate health
      workers on assignment with humanitarian emergency organisations can face more
      clinical situations that require advanced pain control or palliative care.
      Multiple reasons can prevent the provision of this care. AIM:: To better know how
      health workers react to and cope with this dilemma. DESIGN:: A qualitative
      interview study using inductive thematic analysis was performed.
      SETTING/PARTICIPANTS:: A total of 15 expatriate health workers took part in
      individual in-depth interviews after their assignment with the organisation
      'Medecins sans Frontieres'. RESULTS:: Clinical situations requiring advanced pain
      control or palliative care do occur during assignments. Expatriate health workers
      have different levels of knowledge of pain control and palliative care. Lacking
      opioids were a main reason for inadequate pain control. The expatriates felt
      helpless, distressed and frustrated in such situations. Peer support was
      sometimes helpful. Guidelines for palliative care in emergency settings would
      have been useful. CONCLUSION:: Pain control and palliative care needs occur
      during clinical practice in emergency humanitarian assistance. Training for
      expatriate health workers should be improved. Humanitarian organisations should
      strengthen their capacity to provide pain control and palliative care by
      developing and applying adapted guidelines.

PMID- 30113247
TI  - Design and acceptability of a psychosocial text messaging intervention for
      victims of gender-based violence.
AB  - Mobile phones can produce detailed and personalized data to help diagnose, treat,
      prevent or rehabilitate women who are victims of gender violence. We sent
      automatic text messages, based on cognitive-behavioural therapy, to female
      victims of gender violence to assess the feasibility of the medium for mental
      health intervention. During the 28-day intervention period, each woman received
      four automatic text messages every day on a pre-established schedule. We
      evaluated symptoms of depression using the Personal Health Questionnaire-9. The
      Personal Health Questionnaire-9 decreased from an average of 14.8 at the
      beginning of the intervention, to 6.1 at the end of the text messaging period.
      All of the women reported that they liked receiving the messages, they found them
      useful and they felt that the messages had improved their health. Text messages
      are acceptable to women users who are recipients of public health and social
      services. Future research should focus more on the evaluation of the results and
      on how the specific content and aspects of text messaging improve health
      outcomes.

PMID- 30113248
TI  - Multiple Drug Resistance and Virulence Profiling of Salmonella enterica Serovars
      Typhimurium and Enteritidis from Poultry Farms of Faisalabad, Pakistan.
AB  - The zoonotic serovars of Salmonella enterica particularly Typhimurium and
      Enteritidis pose a continuous global threat to poultry industry and public
      health. We report the prevalence of Salmonella Typhimurium and Salmonella
      Enteritidis serovars in local poultry, phenotypic antimicrobial resistance
      profiling, and molecular detection of antimicrobial resistance and virulence
      genes. A total of 340 clinical samples were collected and 239 carried Salmonella,
      which were identified by genus-specific PCR (invA gene) and by matrix-assisted
      laser desorption/ionization time-of-flight. The 68 and 22 isolates were confirmed
      as Salmonella Typhimurium (stm gene) and Salmonella Enteritidis (sdfI gene)
      respectively. Pulsed-field gel electrophoresis (PFGE) revealed 27 and 9 PFGE
      types of Salmonella Typhimurium and Salmonella Enteritidis respectively. Among 24
      antimicrobials tested, highest resistance was observed against pefloxacin while
      highest susceptibility was found for ertapenem in Salmonella Typhimurium and
      aztreonam in Salmonella Enteritidis. All isolates were found multiple drug
      resistant, 98.8% as motile and 8.8% as extended spectrum beta lactamase
      producers. Most prevalent resistance gene in Salmonella Typhimurium was parE
      (69.1%) while in Salmonella Enteritidis blaTEM-1 (72.7%). High prevalence of SopE
      gene in Salmonella Typhimurium (91.1%) and Salmonella Enteritidis (81.8%)
      indicated their zoonotic potential. The study is first of its kind from this
      region and highlights the emerging trends of antimicrobial resistance of global
      concern.

PMID- 30113249
TI  - Prognostic value of cerebrospinal fluid neurofilament light chain and chitinase-3
      like-1 in newly diagnosed patients with multiple sclerosis.
AB  - BACKGROUND: Neurofilament light chain (NFL) and chitinase-3-like-1 (CHI3L1)
      concentrations in cerebrospinal fluid (CSF) may have prognostic value in
      clinically isolated syndromes (CIS) and relapsing-remitting multiple sclerosis
      (RRMS). OBJECTIVES: To compare the prognostic value of CSF concentrations of NFL
      and CHI3L1 in newly diagnosed CIS and RRMS patients. METHODS: NFL and CHI3L1 were
      measured in CSF in 177 newly diagnosed patients with CIS or RRMS who were
      followed clinically for a mean of 5.7 years. RESULTS: At baseline CSF
      concentrations of NFL correlated with CSF concentrations of CHI3L1, relapses in
      the previous year, time from last relapse, and the Expanded Disability Status
      Scale (EDSS) score. CSF concentrations of NFL and CHI3L1 were both associated
      with increased relapse risk during the first 2 years in univariate analyses, but
      only the CSF concentration of NFL was independently associated with relapse risk
      in a multivariable analysis. There was no relationship between CSF concentrations
      of NFL or CHI3L1 and risk of conversion to secondary progressive MS or
      development of disability. CONCLUSION: CSF concentrations of NFL are associated
      with 2-year relapse risk but not with disease progression or clinical worsening
      in newly diagnosed CIS and RRMS patients. This may be due to confounding by the
      effect of disease-modifying therapies.

PMID- 30113250
TI  - Experience of Engagement in a Somatosensory Discrimination Intervention for
      Children with Hemiplegic Cerebral Palsy: A Qualitative Investigation.
AB  - BACKGROUND: To successfully modify an intervention from an adult population for
      use with children with cerebral palsy, it is important to understand the
      components that support a child's motivation and engagement. METHOD: Ten children
      who had participated in the Sense(c) intervention (mean age = 11 years 2 m [SD =
      2 years]; four males; Manual Ability Classification System level I = 1, II = 9)
      and their primary caregivers (N = 11, 10 females) were interviewed. Transcripts
      were analyzed using framework analysis. RESULTS: Key themes were identified in
      the core domains of the Synthesis of Child, Occupational Performance and
      Environment in Time model. Child: children's somatosensory discrimination ability
      improved; Motivation: incorporating child's goals was essential, as were real
      world gains; Environmental: parents were interested in having more involvement in
      the intervention. CONCLUSION: The most engaging elements of the intervention for
      children were the attainment of their self-selected goals. Opportunities to
      modify the intervention for improved partnership with parents were identified.

PMID- 30113251
TI  - Molecular Epidemiology of Plasmid-Mediated Fosfomycin Resistance Gene
      Determinants in Klebsiella pneumoniae Carbapenemase-Producing Klebsiella
      pneumoniae Isolates in China.
AB  - The Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae has become
      a serious problem because the species is wide ranging and there are few treatment
      options. Fosfomycin has attracted renewed interest in combination therapy for
      infections caused by KPC-producing K. pneumoniae isolates. Because of the
      increasing use of fosfomycin, resistant isolates have been continually reported
      in carbapenem-resistant K. pneumoniae (CRKP). At present, multiple mechanisms can
      result in fosfomycin resistance. However, there is limited knowledge with respect
      to plasmid-mediated fosfomycin resistance gene (fosA3) determinants in KPC
      producing K. pneumoniae isolates. In this study, a total of 101 CRKP strains were
      collected from four hospitals in Zhejiang province from January 2013 to August
      2014; 28.7% (29/101) of CRKP isolates were resistant to fosfomycin. Gene fosA3
      was detected in 29 fosfomycin-resistant KPC-producing K. pneumoniae isolates,
      whereas genes fosA, fosB, fosB2, fosC, fosC2, and fosX were all negative among
      the resistant isolates. In addition, among 29 fosfomycin-resistant KPC-producing
      K. pneumoniae isolates, pulsed-field gel electrophoresis (PFGE) analysis revealed
      five pulsotypes. S1-PFGE and Southern blot showed that the fosA3 gene was located
      on an approximately 140-kb plasmid in all isolates. Eight of the 29 isolates
      (27.6%) tested could successfully transfer their fosfomycin-resistant phenotype
      to Escherichia coli strain J53. All fosA3-positive isolates were determined to
      have an identical genetic background, IS26-tetR-cadC-orf1-fosA3-IS26, which is
      the same as that of the fosA3-positive plasmid pFOS18 in China. The primary
      resistance mechanism to fosfomycin was caused by a plasmid-mediated fosA3.
      Furthermore, it is noteworthy that the plasmid genetically carrying a combination
      of the fosA3 and blaKPC-2 genes could accelerate the spread of antibiotic
      resistance. Effective and persistent monitoring and surveillance will be vital to
      prevent further dissemination of these resistance genes.

PMID- 30113252
TI  - Lack of short-chain fatty acids and overgrowth of opportunistic pathogens define
      dysbiosis of neuromyelitis optica spectrum disorders: A Chinese pilot study.
AB  - BACKGROUND: Intestinal microbiota is an important environmental factor in the
      initiation and progression of autoimmune diseases. However, investigations on the
      gut microbiome in neuromyelitis optica spectrum disorders (NMOSD) are relatively
      insufficient, especially for that of the Asia population. OBJECTIVES: To evaluate
      whether or not the intestinal microbiota of NMOSD patients had specific microbial
      signatures. METHODS: Next-generation sequencing and gas chromatography were
      employed to compare the fecal microbial composition and short-chain fatty acids
      (SCFAs) spectrum between patients with NMOSD ( n = 84) and healthy controls ( n =
      54). RESULTS: The gut microbial composition of NMOSD distinguished from healthy
      individuals. Streptococcus, significantly increased in NMOSD, is positively
      correlated with disease severities ( p < 0.05). The use of immunosuppressants
      results in a decrease of Streptococcus, suggesting that Streptococcus might play
      a significant role in the pathogenesis of NMOSD. A striking depletion of fecal
      SCFAs was observed in NMOSD patients ( p < 0.0001), with acetate and butyrate
      showing significantly negative correlation with disease severities ( p < 0.05).
      CONCLUSION: The fecal organismal structures and SCFAs level of patients with
      NMOSD were distinctive from healthy individuals. These findings not only could be
      critical events driving the aberrant immune response responsible for the
      pathogenesis of these disorders but could also provide suggestions for disease
      therapy.

PMID- 30113253
TI  - Vitamin D-binding protein and multiple sclerosis: Evidence, controversies, and
      needs.
AB  - The vitamin D-binding protein (DBP) occupies a key node in the regulation of the
      vitamin D system. Being the main plasma carrier of vitamin D metabolites, it
      regulates their stability and bioavailability. However, DBP is also a
      multifunctional protein with roles in the organism's actin scavenging system and
      immunomodulation. All these activities may affect multiple sclerosis (MS)
      pathophysiology. DBP can be measured in blood and cerebrospinal fluid, body
      fluids that have been investigated as sources of accessible biomarkers of MS.
      Yet, available data on DBP expression and function in MS are scattered and
      somewhat controversial. Aims of this review are to summarize current evidence
      from studies on DBP in MS patients, to discuss possible shortcomings and to
      highlight key points that need to be addressed to gain deeper insight into the
      role of DBP in MS.

PMID- 30113254
TI  - A Comprehensive Meta-Analysis of Spatial Interference From Linguistic Cues:
      Beyond Petrova et al. (2018).

PMID- 30113255
TI  - First Report of Rhizoctonia solani AG-3 Causing Tobacco Target Spot in Yunnan,
      China.

PMID- 30113256
TI  - Occurrence of the Ordinary and the Andean Strains of Potato Virus S Infecting
      Potatoes in the Eastern Region of Kazakhstan.

PMID- 30113257
TI  - First Report of Bean Common Mosaic Necrosis Virus Infecting Soybean in Korea.

PMID- 30113258
TI  - First Report of Lethal Yellowing Associated with Phytoplasma Subgroup 16SrIV-A on
      Silver Date Palm and Chinese Windmill Palm in Louisiana.

PMID- 30113259
TI  - Secondhand Smoke and Streptococcal Infection in Young Children Under Japan's
      Voluntary Tobacco-Free Policy.
AB  - Tobacco-free policy in Japan lags behind those of most developed countries.
      Evidence is required to promote strong implementation of existing policies. This
      study aimed to assess whether exposure to secondhand smoke (SHS) influences the
      incidence of streptococcal infection in young children, to further support the
      need for effective tobacco-free policies in Japan. This study used medical
      administrative claim and health check data from the Japan Health Insurance
      Association Fukuoka branch. Participants were beneficiaries' dependents younger
      than age 4 years. Exposure was defined as SHS from beneficiaries' smoking, each
      year during 2011-2014. The outcome was incidence of streptococcal infection,
      diagnosed with and without laboratory testing. Logistic regression analysis was
      performed to yield odds ratios (ORs) of associations with the outcome and 95%
      confidence intervals (CIs). This study included a total of 5743 children. The
      proportion of all participants with a record of streptococcal infection was 4.2%
      (n = 244). The results of logistic regression analysis between streptococcal
      infection and SHS exposure showed a significantly higher association (OR 1.39,
      95% CI 1.07-1.80, P < 0.05) if all cases were included and an insignificant
      association with diagnoses using testing (OR 1.20, 95% Cl 0.80-1.80, P = 0.39).
      This study showed that 60% of streptococcal infections in young children were
      diagnosed without testing, and SHS increased this incidence regardless of
      testing. It reports new findings regarding the effect of SHS on infection in
      young children to support implementation and promotion of tobacco-free policies
      by the Japanese government not only in public spaces, but also at home.

PMID- 30113260
TI  - The social and psychological health outcomes of team sport participation in
      adults: An integrative review of research.
AB  - AIM: The aim of this article was to review the international scientific research
      literature about the social and psychological health outcomes associated with
      participation in team sport and to synthesise the key issues about team sport as
      a health-promoting activity. METHODS: The methodological framework guiding the
      review process is the integrative research review. A search of 10 key electronic
      databases was conducted to identify both quantitative and qualitative studies
      addressing the social and/or psychological health outcomes from participation in
      a team sport. A total of 6,097 publications were identified and 17 studies met
      the inclusion criteria. RESULTS: A wide range of different positive social,
      psychological, and psychosocial health outcomes associated with team sport
      participation were identified in the studies, with emotional social support,
      sense of belonging, higher self-esteem, social network, and social interaction
      being the most frequently reported health benefits. In addition, three key issues
      influencing the psychological and social health outcomes of team sport
      participation as a health-promoting activity were identified: (1) team sport
      versus individual sport, (2) competitive versus non-competitive structure, and
      (3) commitment and continuation. CONCLUSIONS: There is consistent evidence that
      participation in a team sport is associated with improved social and
      psychological health independent of the type of team sport, age, somatic, or
      mental health problems. The findings indicate that team sport could be more
      efficient in promoting health and ensuring exercise participation and
      continuation than individual sport. However, when utilising team sports for
      health purposes, precautions must be taken with regard to their inherent
      competitive nature.

PMID- 30113262
TI  - Stay Cool During the Hot Summer Months.

PMID- 30113261
TI  - Extent of Health Care Fragmentation in Different Payer Populations: Evidence from
      the Hudson Valley of New York.
AB  - Health care fragmentation occurs when patients see multiple ambulatory providers,
      but no single provider accounts for a substantial proportion of visits. Most
      previous studies have measured fragmentation in Medicare, which may not be
      generalizable. The study objective was to compare the extent of fragmented
      ambulatory care across commercially insured, Medicare, and Medicaid populations.
      The authors conducted a cross-sectional study of adults (N = 256,047) in the
      Hudson Valley region of New York, who were continuously insured (through 5
      commercial payers, Medicare, or Medicaid), were attributed to a primary care
      physician, and had >=4 ambulatory visits in the study year. Fragmentation was
      calculated using a reversed Bice-Boxerman Index, which captures both dispersion
      of care across providers and the relative share of visits by each provider. Chi
      square tests, t tests, and correlation were used to compare patient
      characteristics and patterns of care across payers. Patients with Medicare had
      more chronic conditions (45% had >=5 chronic conditions) than patients with
      commercial insurance (20%) or Medicaid (23%) (P < 0.01). However, mean
      fragmentation scores were comparable across all 3 payer populations: 0.73
      (commercial insurance), 0.74 (Medicare), 0.72 (Medicaid). The correlation between
      number of chronic conditions and fragmentation was weak across payers, ranging
      from r = 0.004 to r = 0.12. If the extent of fragmentation does not vary with
      payer type or with the number of chronic conditions, it suggests that the causes
      of fragmentation may be more numerous and more complex than medical need alone.

PMID- 30113263
TI  - Analysis of phthalate esters in two different baby care products available in
      United Arab Emirates.
AB  - Phthalates are used as plasticizers in a wide range of products and are known to
      affect the human health adversely. Hence, the present study was carried out to
      identify and quantify the presence of four phthalates namely dimethyl phthalate
      (DMP), dibutyl phthalate (DBP), and diethyl phthalate (DEP), di (2-ethylhexyl)
      phthalate (DEHP) in the two baby products i.e. baby oils and baby lotions. The
      daily exposure levels and hazard index of each phthalate were also calculated. It
      was an analytical study where two different brands of samples of baby oil and
      baby lotion each, from the date of manufacturing of 3, 10, and 20 months were
      collected. The extraction of phthalates from different samples was done and
      analyzed using HPTLC. Results showed the presence of all four phthalates,
      although some phthalates were not present in 3 M samples. The maximum
      concentration of all the phthalates was found in 20 M samples. Their
      concentration increased with the storage time indicating the possibility of
      leaching and migration of phthalates from the container into the product. The
      hazard indices for phthalates estimated for baby oil and baby lotion were found
      below 1, which denotes that the daily phthalate exposures are within the
      regulatory limits. It is important to consider that the exposure to phthalates
      can occur not only by dermal contact of these baby products but also through
      other routes. Hence, the study signifies the importance of phthalates
      concentration in such regularly used products.

PMID- 30113264
TI  - Trends in educational and income inequalities in cardiovascular morbidity in
      middle age in Northern Sweden 1993-2010.
AB  - AIMS: Research is scarce regarding studies on income and educational inequality
      trends in cardiovascular disease in Sweden. The aim of this study was to assess
      trends in educational and income inequalities in first hospitalizations due to
      cardiovascular disease (CVD) from 1993 to 2010 among middle-aged women and men in
      Northern Sweden. METHODS: The study comprised repeated cross-sectional register
      data from year 1993-2010 of all individuals aged 38-62 years enrolled in the
      Vasterbotten Intervention Programme (VIP). Data included highest educational
      level, total earned income and first-time hospitalization for CVD from national
      registers. The relative and slope indices of inequality (RII and SII,
      respectively) were used to estimate educational and income inequalities in CVD
      for six subsamples for women and men, and interaction analyses were used to
      estimate trends across time periods. RESULTS: Educational RII and SII were stable
      in women, while they decreased in men. Income inequalities in CVD developed
      differently compared with educational inequalities, with RII and SII for both men
      and women increasing during the study period, the most marked for RII in women
      rising from 1.52 in the 1990s to 2.62 in the late 2000s. CONCLUSIONS: The trend
      of widening income inequalities over 18 years in the middle-aged in Northern
      Sweden, in the face of stable or even decreasing educational inequalities, is
      worrisome from a public health perspective, especially as Swedish authorities
      monitor socioeconomical inequalities exclusively by education. The results show
      that certain social inequalities in CVD rise and persist even within a
      traditionally egalitarian welfare regime.

PMID- 30113265
TI  - Diffusion Tensor Imaging Assessment of Regional White Matter Changes in the
      Cervical and Thoracic Spinal Cord in Pediatric Subjects.
AB  - There are no studies to date,describing changes in the diffusion tensor imaging
      (DTI) metrics of the white matter (WM) regions of the entire cervical and
      thoracic spinal cord (SC) remote from the lesion in pediatric spinal cord injury
      (SCI) subjects. The purpose of this study was to determine whether DTI at sites
      cephalad and caudal to a lesion provides measures of cord abnormalities in
      children with chronic SCI. A retrospective study included 10 typically developing
      subjects (TD) and 10 subjects with chronic SCI who underwent SC imaging in 2014
      2017. Axial diffusion tensor images using an inner field of view DTI sequence
      were acquired to cover the entire cervical and thoracic SC. Regions of interest
      were drawn on the SC WM: right and left lateral (motor), ventral (motor), and
      dorsal (sensory) tracts. To detect differences in DTI metrics between TD and SCI
      of the cord, a one way analysis of variance with pooled t test was performed. A
      stepwise regression analysis was performed to assess the correlation between DTI
      metrics and clinical scores. In motor and sensory tracts, fractional anisotropy
      (FA) and axial diffusivity (AD) were significantly decreased in the proximal
      segments of the caudal cord. In motor tracts cephalad to the lesion, FA was
      significantly decreased whereas AD was significantly increased in the proximal
      segment; however, AD was decreased in the distal and middle segments.
      International Standards for Neurological Classification of Spinal Cord Injury
      (ISNCSCI) total score was significantly correlated with FA and AD of the motor
      and sensory tracts cephalad to the lesion. This study demonstrates that FA and AD
      have the potential to be sensitive biomarkers of the full extent of cord injury
      and might be useful in detecting remote injuries to the SC and in guiding new
      treatments.

PMID- 30113266
TI  - Minocycline Reduces the Severity of Autonomic Dysreflexia after Experimental
      Spinal Cord Injury.
AB  - Spinal cord injury (SCI) is a devastating neurological condition for which there
      is no effective treatment to restore neurological function. The development of
      new treatments for those with SCI may be hampered by the insensitivity of
      clinical tools to assess motor function in humans. Treatments aimed at preserving
      neuronal function through anti-inflammatory pathways (i.e., neuroprotection) have
      been a mainstay of pre-clinical SCI research for decades. Minocycline, a
      clinically available antibiotic agent with anti-inflammatory properties, has
      demonstrated promising neuroprotective effects in a variety of animal models and
      improved motor recovery in a Phase-2 human trial. Here, we leveraged our recently
      developed T3 severe contusion model in the rat to determine the ability of
      minocycline to preserve descending sympathoexcitatory axons and improve
      cardiovascular control after SCI. Forty-one male Wistar rats were randomized to
      either a treatment group (minocycline; n = 20) or a control group (vehicle; n =
      21). All rats received a severe T3 contusion. Minocycline (or vehicle) was
      administered intraperitoneally at one hour post-injury (90 mg/kg), then every 12
      h for two weeks (45 mg/kg). Neuroanatomical correlates (lesion area, descending
      sympathoexcitatory axons) were assessed, in addition to an assessment of
      cardiovascular control (hemodynamics, autonomic dysreflexia) and motor behavior.
      Here, we show that minocycline reduces lesion area, increases the number of
      descending sympathoexctitatory axons traversing the injury site, and ultimately
      reduces the severity of autonomic dysreflexia. Finally, we show that autonomic
      dysreflexia is a more sensitive marker of treatment stratification than motor
      function.

PMID- 30113267
TI  - Blast Exposure Impairs Sensory Gating: Evidence from Measures of Acoustic Startle
      and Auditory Event-Related Potentials.
AB  - Many military service members and veterans who have been exposed to high
      intensity blast waves experience traumatic brain injury (TBI), resulting in
      chronic auditory deficits despite normal hearing sensitivity. The current study
      sought to examine the neurological cause of this chronic dysfunction by testing
      the hypothesis that blast exposure leads to impaired filtering of sensory
      information at brainstem and early cortical levels. Groups of blast-exposed and
      non-blast-exposed participants completed self-report measures of auditory and
      neurobehavioral status, auditory perceptual tasks involving degraded and
      competing speech stimuli, and physiological measures of sensory gating, including
      pre-pulse inhibition and habituation of the acoustic startle reflex and
      electrophysiological assessment of a paired-click sensory gating paradigm. Blast
      exposed participants showed significantly reduced habituation to acoustic startle
      stimuli and impaired filtering of redundant sensory information at the level the
      auditory cortex. Multiple linear regression analyses revealed that poorer sensory
      gating at the cortical level was primarily influenced by a diagnosis of TBI,
      whereas reduced habituation was primarily influenced by a diagnosis of post
      traumatic stress disorder. A statistical model was created including cortical
      sensory gating and habituation to acoustic startle, which strongly predicted
      performance on a degraded speech task. These results support the hypothesis that
      blast exposure impairs central auditory processing via impairment of neural
      mechanisms underlying habituation and sensory gating.

PMID- 30113268
TI  - South Korean Thyroid Cancer Trends: Good News and Bad.

PMID- 30113269
TI  - Rationale and methods of the IDOMENEO health outcomes of the peripheral arterial
      disease revascularisation study in the GermanVasc registry.
AB  - BACKGROUND: Atherosclerotic disease of the lower extremity arteries (PAD) remains
      a significant burden on global healthcare systems with increasing prevalence.
      Various guidelines on the diagnosis and treatment of patients with PAD are
      available but they often lack a sufficient evidence base for high-grade
      recommendations since randomized and controlled trials (RCT) remain rare or are
      frequently subject to conflicts of interest. This registry trial aims to evaluate
      the outcomes of catheter-based endovascular revascularisations vs. open-surgical
      endarterectomy vs. bypass surgery for symptomatic PAD on medical and patient
      reported outcomes. METHODS AND DESIGN: The study is a prospective non-randomized
      multicentre registry trial including invasive revascularisations performed in 10
      000 patients treated for symptomatic PAD at 30 to 40 German vascular centres. All
      patients matching the inclusion criteria are consecutively included for a
      recruitment period of six months (between May and December 2018) or until 10 000
      patients have been included in the study registry. There are three follow-up
      measures at three, six, and 12 months. Automated completeness and plausibility
      checks as well as independent site visit monitoring will be performed to assure
      high internal and external validity of the study data. Study endpoints include
      relevant major cardiovascular and limb events and patient-reported outcomes from
      two Delphi studies with experts in vascular medicine and registry-based research.
      DISCUSSION: It remains unclear if results from RCT can reflect daily treatment
      practice. Furthermore, great costs and complexity make it challenging to
      accomplish high quality randomized trials in PAD treatment. Prospective registry
      based studies to collect real-world evidence can help to overcome these
      limitations.

PMID- 30113270
TI  - Provocative decompression causes diffuse vascular injury in mice mediated by
      microparticles containing interleukin-1beta.
AB  - Inflammatory mediators are known to be elevated in association with decompression
      from elevated ambient pressure, but their role in tissue damage or overt
      decompression sickness is unclear. Circulating microparticles (MPs) are also know
      to increase and because interleukin (IL)-1beta is packaged within these
      particles, we hypothesized that IL-1beta was responsible for tissue injuries.
      Here, we demonstrate that elevations of circulating MPs containing up to 9-fold
      higher concentrations of IL-1beta occur while mice are exposed to high air
      pressure (790 kPa), whereas smaller particles carrying proteins specific to
      exosomes are not elevated. MPs number and intra-particle IL-1beta concentration
      increase further over 13 hours post-decompression. MPs also exhibit intra
      particle elevations of tumor necrosis factor-alpha, caspase-1, inhibitor of
      kappaB kinase -beta and -gamma, and elevated IL-6 is adsorbed to the surface of
      MPs. Contrary to lymphocytes, neutrophil NLRP3 inflammasome oligomerization and
      cell activation parameters occur during high pressure exposure, and additional
      evidence for activation are manifested post-decompression. Diffuse vascular
      damage, while not apparent immediately post-decompression, was present 2 hours
      later and remained elevated for at least 13 hours. Prophylactic administration of
      an IL-1beta receptor inhibitor or neutralizing antibody to IL-1beta inhibited MPs
      elevations, increases of all MPs-associated pro-inflammatory agents, and vascular
      damage. We conclude that an auto-activation process triggered by high pressure
      stimulates MPs production and concurrent inflammasome activation, and IL-1beta is
      a proximal factor responsible for further cytokine production and decompression
      associated vascular injuries.

PMID- 30113271
TI  - Association of physical activity with age-related changes in muscle echo
      intensity in older adults: A 4-year longitudinal study.
AB  - Ultrasonic echo intensity (EI), an easy-to-use measure of intramuscular fat and
      fibrous tissues, is known to increase with aging. However, age-related changes in
      EI have not been examined in a longitudinal design. The objective of this study
      was to investigate 4-year longitudinal changes in the EI of the quadriceps
      femoris in older adults, based on difference in physical activity (PA). This
      study included 131 community-dwelling older adults with a mean age of 72.9 {plus
      minus} 5.2 years. Subcutaneous fat thickness (FT), muscle thickness (MT), and EI
      of the quadriceps femoris were measured by ultrasound. Isometric knee extensor
      strength was also measured. PA was assessed using a questionnaire at baseline,
      and participants were classified into the high- or low-PA groups. In 4 years,
      significant decrease in FT, MT, and strength was observed in both groups (P <
      0.05) while significant decrease in EI was observed only in the high-PA group (P
      < 0.05). Multiple linear regression analyses revealed that the difference in PA
      was a significant predictor of 4-year changes in MT (beta= 0.189, P = 0.031) and
      EI (beta= -3.145, P = 0.045), but not in the body mass index, FT, or strength
      adjusted for potential confounders. The present findings suggest that greater PA
      has a positive effect on longitudinal changes in the MT and EI of the quadriceps
      femoris in older adults. In addition, greater PA may contribute to future
      decrease in EI, and increase in EI may not occur in 4 years even in older adults
      with lesser PA.

PMID- 30113272
TI  - Measurement of nitrate and nitrite in biopsy-sized muscle samples using HPLC.
AB  - Studies of rats have indicated that skeletal muscle plays a central role in whole
      body nitrate (NO3-)/nitrite (NO2-)/nitric oxide (NO) metabolism. Extending these
      results to humans, however, is challenging due to the small size of needle biopsy
      samples. We therefore developed a method to precisely and accurately quantify NO3
      and NO2- in biopsy-sized muscle samples. NO3- and NO2- were extracted from rat
      soleus samples using methanol combined with mechanical homogenization +
      ultrasound, bead beating, pulverization at liquid N2 temperature, or
      pulverization + 0.5% Triton X-100. After centrifugation to remove proteins, NO3-
      and NO2- were measured using HPLC. Mechanical homogenization + ultrasound
      resulted in the lowest NO3- content (62{plus minus}20 pmol/mg), with high
      variability (CV >50%) across samples from the same muscle. The NO2-:NO3- ratio
      (0.019{plus minus}0.006) was also elevated, suggestive of NO3- reduction during
      tissue processing. Bead beating or pulverization yielded lower NO2- and slightly
      higher NO3- levels, but reproducibility was still poor. Pulverization + 0.5%
      Triton X-100 provided the highest NO3- content (124{plus minus}12 pmol/mg) and
      lowest NO2-:NO3- ratio (0.008{plus minus}0.001), with the least variability
      between duplicate samples (CV ~15%). These values are consistent with literature
      data from larger rat muscle samples analyzed using chemiluminescence. Samples
      were stable for at least 5 wk at -80{degree sign} C provided residual xanthine
      oxidoreductase activity was blocked using 0.1 mmol/L oxypurinol. We have
      developed a method capable of measuring NO3- and NO2- in <1 mg of muscle. This
      method should prove highly useful in investigating the role of skeletal muscle in
      NO3-/NO2-/NO metabolism in human health and disease.

PMID- 30113273
TI  - Muscle type-specific RNA polymerase II recruitment during PGC-1alpha gene
      transcription after acute exercise in adult rats.
AB  - Epigenetic regulation of gene expression differs between fast- and slow-twitch
      skeletal muscles in adult rats, although the precise mechanisms are still
      unknown. The present study investigates the differences in responses of RNA
      polymerase II (Pol II) and histone acetylation during transcriptional activation
      in the plantaris and soleus muscles of adult rats after acute treadmill running.
      We targeted the peroxisome proliferator-activated receptor gamma coactivator 1
      alpha (PGC-1alpha) gene to analyze epigenomic changes by chromatin
      immunoprecipitation. The mRNA expression of the PGC-1alpha-b isoform was
      significantly up-regulated in both plantaris and soleus muscles 2 h after acute
      running, although the magnitude of the up-regulation was more pronounced in the
      plantaris muscle. The sequences of proximal exons of the PGC-1alpha locus were
      expressed more in the plantaris muscle after acute running. Accumulation of Pol
      II was noted near the alternative exon 1 in both plantaris and soleus muscles in
      association with the enhanced distribution of acetylated histone 3. Accumulation
      of Pol II was also observed at the transcription start site, exon 2, and exon 3
      in the plantaris muscle, but not the soleus muscle. It was noted that in the
      soleus muscle, acetylation of histone 3 at lysine 27 was enhanced throughout the
      PGC-1alpha locus in response to transcriptional activation, suggesting that
      elongating Pol II was capable of traveling through to the end of the locus. These
      results indicate that the mobility of Pol II during PGC-1alphatranscription
      differed between fast- and slow-twitch skeletal muscles, affecting the strength
      of the transcriptional activity.

PMID- 30113274
TI  - Psychometric properties of the Persian version of Neal and Griffin's safety
      performance scale.
AB  - INTRODUCTION: Neal and Griffin's safety performance scale is an appropriate tool
      to evaluate safety performance. This article was validated and relied on the
      Persian version of Neal and Griffin's scale as the widely used tool to assess
      safety performance. METHODS: Neal and Griffin's scale has eight questions and two
      dimensions - safety compliance and safety participation. A back-forward method
      was used to translate the original English version into Persian. A total of 161
      employees of a petrochemical complex were selected for data collection. Content
      validity, Cronbach's alpha and split-half methods, concurrent validity and
      confirmatory factor analysis were used for psychometric evaluation. RESULTS: The
      content validity index and content validity ratio were 0.82 and 0.84,
      respectively. Cronbach's alpha for total items was 0.9, indicating a high
      consistency. Additionally, Cronbach's alpha values for safety compliance and
      safety participation were 0.87 and 0.83, respectively. Spearman's correlation
      coefficients indicated a positive correlation between safety performance and
      safety culture items (r = 0.182-0.852, p < 0.01). Goodness-of-fit indexes in the
      default model had poor values. Thus, these values were improved in the modified
      model. CONCLUSION: The results demonstrated that Neal and Griffin's scale could
      be a reliable tool to evaluate preventive measures of safety performance among
      Iranian workers.

PMID- 30113275
TI  - Developing a Mental Health Measurement Strategy to Capture Psychological Problems
      among Lower Caste Adolescent Girls in Rural, South India.
AB  - Adolescent girls vulnerable to early marriage and school dropout in rural India
      may be at elevated risk of psychosocial problems. However, few screening
      instruments have been culturally adapted and validated to measure this risk. This
      paper describes the process by which the Primary Health Questionnaire PHQ-9, a
      screening instrument for depression, was tested for cultural validity as part of
      the Samata evaluation - an intervention to support low caste adolescent girls in
      rural south India to attend and complete secondary school and to delay marriage
      until adulthood. Three focus groups discussions (FGDs) were held with 20
      adolescent girls and six outreach workers of the Samata programme in rural north
      Karnataka, south India. The FGDs were used to explore local expressions of
      psychosocial problems and to understand the acceptability and appropriateness of
      PHQ-9 items. A thematic content analysis was conducted on the transcripts of the
      FGDs. Descriptions of local expressions of psychosocial problems generally
      matched the items on the PHQ-9. However, not all representations of psychological
      symptoms were captured by this tool. Persistent worry, loneliness and isolation,
      and externalised behaviours were also described by participants as common
      expressions of psychosocial distress. Based on the limitations of translation
      methods, local stakeholders must be involved in evaluating the cultural
      appropriateness of mental health screening tools. The current research
      demonstrates a strategy by which to assess the cultural validity of Western
      psychiatric instruments with key stakeholders in low- and middle-income settings.

PMID- 30113276
TI  - Some People May Need it, But Not Me, Not Now: Seeking Professional Help for
      Mental Health Problems in Urban China.
AB  - In recent years, various levels of the Chinese government have undertaken the
      task of developing new models of community-based mental health services. Greater
      availability and higher quality will not result in substantial improvements if
      those suffering from mental illnesses do not use the services. This article
      examines not only people's cultural perception of mental health and help-seeking
      but also their practical concerns and preferences about mental health service
      provision in urban China. The study analyzes qualitative data from in-depth
      interviews with 50 respondents who belong to the most psychologically distressed
      subgroup (with the Kessler Psychological Distress Scale (K10) score >= 25)
      identified in a household survey in Beijing. While stigma about mental illness
      and help-seeking is real and well described, most interviewees are also not aware
      of the availability of professional mental health services. They believe that
      professional services target the upper-middle and upper classes, and are outside
      the sphere of their daily life and socio-economic status. The interviewees do not
      welcome the prospect of a mental health clinic or treatment center in their
      neighborhood due to concerns about stigma and confidentiality; instead, they
      support the creation of mental health referral services and promotion programs
      within the community or on the Internet. The findings suggest that the
      development of community-based mental health services in mainland China should
      take into account not only the cultural constraints that make people reluctant to
      seek professional help but also the structural inadequacies that deter potential
      user groups from accessing such services.

PMID- 30113277
TI  - Executive Functions and Their Relation to Sleep Following Mild Traumatic Brain
      Injury in Preschoolers.
AB  - OBJECTIVES: Traumatic brain injury (TBI) sustained during childhood is known to
      impact children's executive functioning. However, few studies have focused
      specifically on executive functioning after preschool TBI. TBI has also been
      associated with sleep disturbances, which are known to impair executive functions
      in healthy children. The aim of this study was to investigate executive functions
      in preschoolers with mild TBI, and to determine the role of sleep in the links
      between TBI and executive functioning. METHODS: The sample was drawn from a
      longitudinal study and included 167 children, aged 18 to 60 months, divided into
      2 groups: children with accidental mild TBI (n=84) and typically developing
      children (n=83). Children were assessed 6 months post-injury on executive
      function measures (inhibition and cognitive flexibility) and sleep measures
      (actigraphy data and parental rating of sleep problems). RESULTS: The two groups
      did not differ in their executive abilities. However, relative to controls,
      children with mild TBI and shorter nighttime sleep duration or increased sleep
      problems exhibited poorer executive functions. CONCLUSIONS: These results support
      a "double hazard" effect, whereby the combination of sleep disturbances and mild
      TBI results in poorer executive functions. The findings highlight the importance
      of assessing and monitoring the quality of sleep even after mild head injuries.
      Poor sleep may place children at risk for increased cognitive difficulties.
      (JINS, 2018, 24, 769-780).

PMID- 30113278
TI  - Maternal and neonatal characteristics of a Canadian urban cohort receiving
      treatment for opioid use disorder during pregnancy.
AB  - The epidemic of prescription and non-prescription opioid misuse is of particular
      importance in pregnancy. The Society of Obstetricians and Gynaecologists of
      Canada currently recommends opioid replacement therapy with methadone or
      buprenorphine for opioid-dependent women during pregnancy. This vulnerable
      segment of the population has been shown to be at increased risk of blood-borne
      infectious diseases, nutritional insecurity and stress. The objective of this
      study was to describe an urban cohort of pregnant women on opioid replacement
      therapy and to evaluate potential effects on the fetus. A retrospective chart
      review of all women on opioid replacement therapy and their infants who delivered
      at The Ottawa Hospital General and Civic campuses between January 1, 2013 and
      March 24, 2017 was conducted. Data were collected on maternal characteristics,
      pregnancy outcomes, neonatal outcomes and corresponding placental pathology.
      Maternal comorbidities identified included high rates of infection, tobacco use
      and illicit substance use, as well as increased rates of placental abruption
      compared with national averages. Compared with national baseline averages, the
      mean neonatal birth weight was low, and the incidence of small for gestational
      age infants and congenital anomalies was high. The incidence of NAS was
      comparable with estimates from other studies of similar cohorts. Findings support
      existing literature that calls for a comprehensive interdisciplinary risk
      reduction approach including dietary, social, domestic, psychological and other
      supports to care for opioid-dependent women in pregnancy.

PMID- 30113279
TI  - Does hut climate matter for piglet survival in organic production?
AB  - Piglet mortality in outdoor production systems varies across the year, and a
      reason for this variation could be fluctuations in hut climate, as ambient
      temperature might influence piglet survival, both directly and indirectly.
      Therefore, the aim of the current study was to investigate the impact of
      farrowing hut climate and year variation on stillbirth and liveborn mortality. A
      large-scale observational study was conducted at five commercial organic pig
      producing herds in Denmark from June 2015 to August 2016. Both year variation (F
      3,635=4.40, P=0.004) and farrowing hut temperature (F 2,511=6.46, P=0.002)
      affected the rate of stillbirths. The risk of stillborn piglets was lowest in
      winter and during this season larger changes in hut temperature between day 1
      prepartum and the day of farrowing increased the risk of stillbirths (F
      1,99=6.39, P=0.013). In addition, during the warm part of the year stillbirth
      rate increased at temperatures ?27 degrees C. Year variation also affected
      liveborn mortality (F 3,561=3.86, P=0.009) with a lower rate of liveborn deaths
      in spring. However, the hut climate did not influence liveborn deaths.
      Consequently, other factors than hut climate may explain the influence of year
      variation on liveborn mortality. These could be light differences causing
      seasonality in reproduction and lactation.

PMID- 30113280
TI  - New Yes/No Recognition Memory Analysis on the California Verbal Learning Test-3:
      Clinical Utility in Alzheimer's and Huntington's Disease.
AB  - OBJECTIVES: The third edition of the California Verbal Learning Test (CVLT-3)
      includes a new index termed List A versus Novel/Unrelated recognition
      discriminability (RD) on the Yes/No Recognition trial. Whereas the Total RD index
      incorporates false positive (FP) errors associated with all distractors
      (including List B and semantically related items), the new List A versus
      Novel/Unrelated RD index incorporates only FP errors associated with novel,
      semantically unrelated distractors. Thus, in minimizing levels of source and
      semantic interference, the List A versus Novel/Unrelated RD index may yield purer
      assessments of yes/no recognition memory independent of vulnerability to source
      memory difficulties or semantic confusion, both of which are often seen in
      individuals with primarily frontal-system dysfunction (e.g., early Huntington's
      disease [HD]). METHODS: We compared the performance of individuals with
      Alzheimer's disease (AD) and HD in mild and moderate stages of dementia on CVLT-3
      indices of Total RD and List A versus Novel/Unrelated RD. RESULTS: Although AD
      and HD subgroups exhibited deficits on both RD indices relative to healthy
      comparison groups, those with HD generally outperformed those with AD, and group
      differences were more robust on List A versus Novel/Unrelated RD than on Total
      RD. CONCLUSIONS: Our findings highlight the clinical utility of the new CVLT-3
      List A versus Novel/Unrelated RD index, which (a) maximally assesses yes/no
      recognition memory independent of source and semantic interference; and (b)
      provides a greater differentiation between individuals whose memory disorder is
      primarily at the encoding/storage level (e.g., as in AD) versus at the retrieval
      level (e.g., as in early HD). (JINS, 2018, 24, 833-841).

PMID- 30113284
TI  - Stratification of the risk of bipolar disorder recurrences in pregnancy and
      postpartum.
AB  - BACKGROUND: Pregnancy and childbirth are a period of high risk for women with
      bipolar disorder and involve difficult decisions particularly about continuing or
      stopping medications.AimsTo explore what clinical predictors may help to
      individualise the risk of perinatal recurrence in women with bipolar disorder.
      METHOD: Information was gathered retrospectively by semi-structured interview,
      questionnaires and case-note review from 887 women with bipolar disorder who have
      had children. Clinical predictors were selected using backwards stepwise logistic
      regression, conditional permutation random forests and reinforcement learning
      trees. RESULTS: Previous perinatal history of affective psychosis or depression
      was the most significant predictor of a perinatal recurrence (odds ratio (OR) =
      8.5, 95% CI 5.04-14.82 and OR = 3.6, 95% CI 2.55-5.07 respectively) but even
      parous women with bipolar disorder without a previous perinatal mood episode were
      at risk following a subsequent pregnancy, with 7% developing postpartum
      psychosis. CONCLUSIONS: Previous perinatal history of affective psychosis or
      depression is the most important predictor of perinatal recurrence in women with
      bipolar disorder and can be used to individualise risk assessments.Declaration of
      interestNone.

PMID- 30113285
TI  - Rise of the machines? Machine learning approaches and mental health:
      opportunities and challenges.
AB  - SummaryMachine learning methods are being increasingly applied to physical
      healthcare. In this article we describe some of the potential benefits,
      challenges and limitations of this approach in a mental health context. We
      provide a number of examples where machine learning could add value beyond
      conventional statistical modelling.Declaration of interestNone.

PMID- 30113282
TI  - Use of schizophrenia and bipolar disorder polygenic risk scores to identify
      psychotic disorders.
AB  - BACKGROUND: There is increasing evidence for shared genetic susceptibility
      between schizophrenia and bipolar disorder. Although genetic variants only convey
      subtle increases in risk individually, their combination into a polygenic risk
      score constitutes a strong disease predictor.AimsTo investigate whether
      schizophrenia and bipolar disorder polygenic risk scores can distinguish people
      with broadly defined psychosis and their unaffected relatives from controls.
      METHOD: Using the latest Psychiatric Genomics Consortium data, we calculated
      schizophrenia and bipolar disorder polygenic risk scores for 1168 people with
      psychosis, 552 unaffected relatives and 1472 controls. RESULTS: Patients with
      broadly defined psychosis had dramatic increases in schizophrenia and bipolar
      polygenic risk scores, as did their relatives, albeit to a lesser degree.
      However, the accuracy of predictive models was modest. CONCLUSIONS: Although
      polygenic risk scores are not ready for clinical use, it is hoped that as they
      are refined they could help towards risk reduction advice and early interventions
      for psychosis.Declaration of interestR.M.M. has received honoraria for lectures
      from Janssen, Lundbeck, Lilly, Otsuka and Sunovian.

PMID- 30113289
TI  - Security of mind: 20 years of attachment theory and its relevance to psychiatry.
AB  - SummaryIn this editorial, I suggest that no psychiatrist should be without a
      working knowledge of attachment theory, and it is a capability that all trainees
      should cover in the proposed new curriculum. I have focused on three domains of
      research to argue that attachment theory is relevant to practicing
      psychiatrists.Declaration of interestNone.

PMID- 30113288
TI  - Fractional anisotropy of the uncinate fasciculus and cingulum in bipolar disorder
      type I, type II, unaffected siblings and healthy controls.
AB  - BACKGROUND: Fractional anisotropy in the uncinate fasciculus and the cingulum may
      be biomarkers for bipolar disorder and may even be distinctly affected in
      different subtypes of bipolar disorder, an area in need of further
      research.AimsThis study aims to establish if fractional anisotropy in the
      uncinate fasciculus and cingulum shows differences between healthy controls,
      patients with bipolar disorder type I (BD-I) and type II (BD-II), and their
      unaffected siblings. METHOD: Fractional anisotropy measures from the uncinate
      fasciculus, cingulum body and parahippocampal cingulum were compared with
      tractography methods in 40 healthy controls, 32 patients with BD-I, 34 patients
      with BD-II, 17 siblings of patients with BD-I and 14 siblings of patients with BD
      II. RESULTS: The main effects were found in both the right and left uncinate
      fasciculus, with patients with BD-I showing significantly lower fractional
      anisotropy than both patients with BD-II and healthy controls. Participants with
      BD-II did not differ from healthy controls. Siblings showed similar effects in
      the left uncinate fasciculus. In a subsequent complementary analysis, we
      investigated the association between fractional anisotropy in the uncinate
      fasciculus and polygenic risk for bipolar disorder and psychosis in a large
      cohort (n = 570) of healthy participants. However, we found no significant
      association. CONCLUSIONS: Fractional anisotropy in the uncinate fasciculus
      differs significantly between patients with BD-I and patients with BD-II and
      healthy controls. This supports the hypothesis of differences in the
      physiological sub-tract between bipolar disorder subtypes. Similar results were
      found in unaffected siblings, suggesting the potential for this biomarker to
      represent an endophenotype for BD-I. However, fractional anisotropy in the
      uncinate fasciculus seems unrelated to polygenic risk for bipolar disorder or
      psychosis.Declaration of interestNone.

PMID- 30113291
TI  - Neurotrophins, cytokines, oxidative stress mediators and mood state in bipolar
      disorder: systematic review and meta-analyses.
AB  - BACKGROUND: A reliable biomarker signature for bipolar disorder sensitive to
      illness phase would be of considerable clinical benefit. Among circulating blood
      derived markers there has been a significant amount of research into inflammatory
      markers, neurotrophins and oxidative stress markers.AimsTo synthesise and
      interpret existing evidence of inflammatory markers, neurotrophins and oxidative
      stress markers in bipolar disorder focusing on the mood phase of illness. METHOD:
      Following PRISMA (Preferred Reporting Items for Systematic reviews and Meta
      analyses) guidelines, a systematic review was conducted for studies investigating
      peripheral biomarkers in bipolar disorder compared with healthy controls. We
      searched Medline, Embase, PsycINFO, SciELO and Web of Science, and separated
      studies by bipolar mood phase (mania, depression and euthymia). Extracted data on
      each biomarker in separate mood phases were synthesised using random-effects
      model meta-analyses. RESULTS: In total, 53 studies were included, comprising 2467
      cases and 2360 controls. Fourteen biomarkers were identified from meta-analyses
      of three or more studies. No biomarker differentiated mood phase in bipolar
      disorder individually. Biomarker meta-analyses suggest a combination of high
      sensitivity C-reactive protein/interleukin-6, brain derived neurotrophic
      factor/tumour necrosis factor (TNF)-alpha and soluble TNF-alpha receptor 1 can
      differentiate specific mood phase in bipolar disorder. Several other biomarkers
      of interest were identified. CONCLUSIONS: Combining biomarker results could
      differentiate individuals with bipolar disorder from healthy controls and
      indicate a specific mood-phase signature. Future research should seek to test
      these combinations of biomarkers in longitudinal studies.Declaration of
      interestNone.

PMID- 30113293
TI  - Kaleidoscope.

PMID- 30113294
TI  - Impulsivity, Attachment, and Relational Psychopathology.

PMID- 30113295
TI  - Codon pair bias deoptimization of the major oncogene meq of a very virulent
      Marek's disease virus.
AB  - Codon pair bias deoptimization (CPBD) has been successfully used to attenuate
      several RNA viruses. CPBD involves recoding a viral protein-coding sequence to
      maximize the number of codon pairs that are statistically underrepresented in the
      host, which presumably slows protein translation and, hence, causes virus
      attenuation. However, since recoding preserves the amino acid composition and
      codon bias, attenuated and parental viruses are antigenically identical. To
      determine if Marek's disease virus (MDV), a highly oncogenic herpesvirus of the
      chicken with a large double-stranded DNA genome, can be attenuated by CPBD of its
      major oncogene meq, we recoded the gene to minimize (meq-D), maximize (meq-O), or
      preserve (meq-R) the level of codon pairs that are overrepresented in the chicken
      protein-coding sequences. Unexpectedly, mutants carrying recoded genes produced
      comparable or increased levels of Meq in the context of viral infection in
      cultured cells. In addition, parental virus and mutant viruses carrying recoded
      meq genes replicated with comparable kinetics in vitro and in vivo, and were
      equally virulent in susceptible chickens. In summary, CPBD of meq failed to
      produce any quantifiable attenuation of MDV and confirms differences in the
      complexity of applying CPBD to large DNA viruses versus RNA viruses.

PMID- 30113296
TI  - Drechmeria panacis sp. nov., an endophyte isolated from Panax notoginseng.
AB  - An endophytic strain (designated as strain SYPF 8335T) was isolated from a root
      of Panax notoginseng in Wenshan district, Yunnan province of China. Strain SYPF
      8335T grew very slowly and formed white colonies. Phylogenetic analysis of four
      loci indicated that strain SYPF 8335T was placed in the Drechmeria clade with
      Drechmeria campanulata as its closest phylogenetic neighbour. The nucleotide
      differences between strain SYPF 8335T and D. campanulata are 30 substitutions in
      the internal transcriber region region. A key morphological feature that
      differentiates the two fungi is that D. campanulata produces campanulate conidia.
      Combined with the morphology and molecular analyses, a new species named
      Drechmeria panacis sp. nov., is proposed.

PMID- 30113297
TI  - Differences in the effects of mutations in GP131, a guinea pig cytomegalovirus
      homologue of pentameric complex component UL130, on macrophage and epithelial
      cell infection.
AB  - As congenital cytomegalovirus (CMV) infection is the major cause of developmental
      abnormalities in children, the development of effective vaccines is critical to
      public health. Recent studies have demonstrated that the pentameric complex
      (Pentamer) of glycoproteins, which is required for human CMV infection of
      endothelial and epithelial cells, could be a potent vaccine antigen. As guinea
      pig CMV (GPCMV) infects congenitally and encodes homologues of all Pentamer
      components, GPCMV models are considered to be useful for the development of
      vaccine strategies. Here, to clarify the precise requirement of GP131, one of the
      GPCMV Pentamer components, for the infection of epithelial cells and macrophages,
      we prepared several mutants with a charged amino acid-to-alanine alteration in
      GP131 and found some differences in the effects of the mutations on the infection
      of the two cell types, suggesting the existence of cell type-dependent
      recognition or function of Pentamer in GPCMV infection.

PMID- 30113298
TI  - FliW controls growth-phase expression of Campylobacter jejuni flagellar and non
      flagellar proteins via the post-transcriptional regulator CsrA.
AB  - Campylobacter jejuni is an important human pathogen that causes 96 million cases
      of acute diarrheal disease worldwide each year. We have shown that C. jejuni CsrA
      is involved in the post-transcriptional regulation of more than 100 proteins, and
      altered expression of these proteins is presumably involved in the altered
      virulence-related phenotypes of a csrA mutant. Mutation of fliW results in C.
      jejuni cells that have greatly truncated flagella, are less motile, less able to
      form biofilms, and exhibit a reduced ability to colonize chicks. The loss of FliW
      results in the altered expression of 153 flagellar and non-flagellar proteins,
      the majority of which are members of the CsrA regulon. The number of proteins
      dysregulated in the fliW mutant was greater at mid-log phase (120 proteins) than
      at stationary phase (85 proteins); 52 proteins showed altered expression at both
      growth phases. Loss of FliW altered the growth-phase- and CsrA-mediated
      regulation of FlaA flagellin. FliW exerts these effects by binding to both FlaA
      and to CsrA, as evidenced by pull-down assays, protein-protein cross-linking, and
      size-exclusion chromatography. Taken together, these results show that CsrA
      mediated regulation of both flagellar and non-flagellar proteins is modulated by
      direct binding of CsrA to the flagellar chaperone FliW. Changing FliW:CsrA
      stoichiometries at different growth phases allow C. jejuni to couple the
      expression of flagellar motility to metabolic and virulence characteristics.

PMID- 30113299
TI  - Thauera hydrothermalis sp. nov., a thermophilic bacterium isolated from hot
      spring.
AB  - A Gram-stain-negative, non-spore-forming, rod-shaped, motile bacterial strain,
      designated GD-2T, was isolated from a sediment sample collected from a hot spring
      in the Tibet Autonomous Region, China. Strain GD-2T grew at a temperature range
      of 37-55  degrees C (optimum, 45-50  degrees C), a pH range of 5.5-11.0 (pH 7.0
      7.5) and a NaCl concentration range of 0-4.0 % (0 %). The phylogenetic analysis
      based on 16S rRNA gene sequencing showed that strain GD-2T represented a member
      of the genus Thauera within the family Zoogloeaceae. Strain GD-2T was closely
      related to Thauera linaloolentis 47LolT with the highest 16S rRNA gene sequence
      similarity of 95.5 %. The whole genomic average nucleotide identity value for GD
      2T and 47LolT was 75.3 %. The predominant cellular fatty acids of the strain were
      C16 : 0, summed feature 3 (C16 : 1omega6c and/or C16 : 1omega7c), C10 : 0 3-OH
      and C12 : 0. The main polar lipids were phosphatidylethanolamine,
      phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids
      and two unidentified aminolipids. The major isoprenoid quinone was ubiquinone 8.
      Genome sequencing revealed that the genome size of GD-2T was 3 059 321 bp with a
      G+C content of 63.57 mol%. On the basis of phylogenetic, phenotypic and
      chemotaxonomic characteristics, strain GD-2T is considered to represent a novel
      species of the genus Thauera, for which the name Thauera hydrothermalis sp. nov.
      is proposed. The type strain is GD-2T (=NBRC 112472T=CGMCC 1.15527T).

PMID- 30113300
TI  - Simulacricoccus ruber gen. nov., sp. nov., a microaerotolerant, non-fruiting,
      myxospore-forming soil myxobacterium and emended description of the family
      Myxococcaceae.
AB  - A non-fruiting group of myxobacteria was previously speculated to exist in nature
      based on metagenomics data containing uncultured members of the order
      Myxococcales. Here, we describe a myxobacterial strain, designated MCy10636T,
      which was isolated from a German soil sample collected in 2013. It exhibits
      swarming characteristics but atypically produces myxospores in the absence of
      fruiting bodies. The novel strain stains Gram-negative and Congo-red-negative and
      is characterized mesophilic, neutrophilic, chemoheterotrophic and
      microaerotolerant. Branched-chain fatty acids are the predominant cellular fatty
      acids over the straight-chain type, and contain the major fatty acids iso-C17 : 0
      2-OH, C16 : 1, iso-C17 : 0 and iso-C15 : 0. Based on blastn results, the 16S rRNA
      gene sequence reveals similarity (97 %) to Aggregicoccus edonensis MCy1366T, (97
      %) Myxococcus macrosporus DSM 14697T, (96 %) Corallococcus coralloides DSM2259T
      and Corallococcus exiguus Cc e167T. Phylogenetic analysis showed a novel lineage
      of MCy10636T in the family Myxococcaceae, suborder Cystobacterineae. Based on
      polyphasic taxonomic characterization, we propose that this unusual, non
      fruiting, myxospore-forming and microaerotolerant myxobacterial strain,
      MCy10636T, represents a novel genus and species, Simulacricoccus ruber gen. nov.,
      sp. nov. (DSM 106554T=NCCB 100651T).

PMID- 30113302
TI  - Proposal to emend Rules 50a and 50b of the International Code of Nomenclature of
      Prokaryotes.
AB  - Rules 50a and 50b of the International Code of Nomenclature of Prokaryotes
      respectively regulate the elevation of a subspecies to the rank of a species and
      the lowering of a species to the rank of subspecies. The Code does not indicate
      that the resulting new names must be considered new combinations, as the cases
      described in Rules 50a and 50b are not covered by Rule 34a. Based on the rules of
      the Code, new combination events are applicable only at the identical rank, and
      therefore new combination events and new species/subspecies events are mutually
      exclusive. In spite of this there have been at least 44 cases in which the new
      names were described as comb. nov. during elevation in rank from subspecies to
      species and at least 30 such cases during lowering in rank from species to
      subspecies. To prevent confusion in the future we propose adding notes to Rules
      50a and 50b to clarify the issue.

PMID- 30113301
TI  - Flagellimonas aquimarina sp. nov., and transfer of Spongiibacterium flavum Yoon
      and Oh 2012 and S. pacificum Gao et al. 2015 to the genus Flagellimonas Bae et
      al. 2007 as Flagellimonas flava comb. nov. and F. pacifica comb. nov.,
      respectively.
AB  - A Gram-stain-negative, non-spore-forming, rod-shaped, aerobic and diffusible
      yellow-coloured bacterial strain, designated strain ECD12T was isolated from a
      seaweed, Ecklonia cava. The isolate required sea salts for growth. Catalase
      positive and oxidase-negative. A phylogenetic tree based on 16S rRNA gene
      sequences showed that strain ECD12T formed an evolutionary lineage within the
      radiation enclosing the members of genera Spongiibacterium and Flagellimonas
      sharing the highest similarity to Flagellimonas eckloniae DOKDO007T (96.8 % 16S
      rRNA gene sequence similarity) followed by Spongiibacterium pacificum SW169T
      (96.4 %) and Spongiibacterium flavum DSM 22638T (96.1 %). The major fatty acids
      were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The new isolate contained
      MK-6 as the only isoprenoid quinone and phosphatidylethanolamine, two
      unidentified amino lipids and two unidentified lipids as the major polar lipids.
      The genomic DNA G+C content is 39 mol%. A number of phenotypic characteristics
      such as the production of diffusible pigment distinguished strain ECD12T from the
      related species. On the basis of the evidence presented in this study, a novel
      species, Flagellimonas aquimarina sp. nov., is proposed for strain ECD12T (=KCTC
      52351T=JCM 32292T). Based on the sequence similarity, phylogenetic relationship
      and common morphological, physiological and chemical characters among the members
      of the genera Spongiibacterium and Flagellimonas, it is recommended that the two
      genera are combined into a single genus. Thus, transfer of S. flavumYoon and Oh
      2012 and S. pacificum Gao et al. 2015 to the genus FlagellimonasBae et al. 2007
      as Flagellimonas flava comb. nov. and Flagellimonas pacifica comb. nov.,
      respectively, is also proposed.

PMID- 30113303
TI  - Aerosolization of Mycobacterium avium and Mycobacterium abscessus from a
      household ultrasonic humidifier.
AB  - PURPOSE: To measure the aerosolization of Mycobacterium avium subspecies
      hominissuis and Mycobacterium abscessus subspecies abscessus from ultrasonic
      humidifiers. METHODOLOGY: An ultrasonic humidifier was filled with sterile tap
      water and inoculated with water-acclimated cells of either the M. avium or M.
      abscessus strains to achieve a range of densities similar to those of
      mycobacteria found in drinking waters. During operation of the humidifier,
      aerosols were collected using an Andersen 6-Stage Cascade Sampler. RESULTS: Cells
      of the M. avium and M. abscessus strains were readily aerosolized and recovered
      in particles (1-5 um diameter); small enough to enter the furthest reaches of the
      human lung. Aerosolization of M. abscessus was significantly reduced in the
      presence of a normal drinking water bacterial flora. Significantly greater
      numbers of M. avium cells were aerosolized from high-density suspensions (1200
      c.f.u. ml-1), than from low-density (120 c.f.u. ml-1) and very low-density (12
      c.f.u. ml-1) suspensions. CONCLUSIONS: This report documents the potential for M.
      avium subspecies hominissuis and M. abscessus subspecies abscessus cells in
      drinking water to be aerosolized from one type of portable humidifier; an
      ultrasonic humidifier. Care should be taken in using an ultrasonic humidifier
      where an individual at risk for mycobacterial pulmonary disease could be exposed.

PMID- 30113304
TI  - Inactivation of invertase enhances sucrose production in the cyanobacterium
      Synechocystis sp. PCC 6803.
AB  - Sucrose is naturally synthesized by many cyanobacteria under high salt
      conditions, which can be applied to produce this widely used feedstock. To
      improve sucrose production with the moderate halo-tolerant cyanobacterium
      Synechocystis sp. PCC 6803, we identified and biochemically characterized the
      sucrose-degrading invertase. Inactivating the invertase encoding gene sll0626
      (inv) significantly increased cellular sucrose levels; interestingly sucrose over
      accumulation was also observed under NaCl-free conditions. The subsequent
      inactivation of inv in the mutant DeltaggpS, which cannot synthesize the major
      compatible solute glucosylglycerol, resulted in further enhanced sucrose
      accumulation in the presence of 1.5 % NaCl. Then, inv mutation was introduced
      into the previously obtained sucrose-producing strain WD25 (Du W, Liang F, Duan
      Y, Tan X, Lu X. Metab Eng 2013;19:17-25), which resulted in almost 40 % higher
      sucrose accumulation. These findings show that invertase is an interesting target
      in obtaining efficient sucrose production in cyanobacterial host cells.

PMID- 30113305
TI  - Characterization of pelvic and cervical microbiotas from patients with pelvic
      inflammatory disease.
AB  - PURPOSE: The aims of this work were: (i) to profile and compare pelvic and
      cervical microbiota from patients with pelvic inflammatory disease (PID); (ii) to
      test the ascending infection hypothesis that the microbes in the vagina or cervix
      spread to the upper genital tract and cause PID. METHODOLOGY: Thirty-eight PID
      patients and 19 control patients were enrolled in this study and received
      salpingectomy or salpingo-oophorectomy. Both pelvic and cervical samples were
      collected during surgery, which were subject to culture diagnosis and next
      generation sequencing (NGS)-based 16S rRNA profiling. RESULTS: For the PID group,
      the NGS-based method revealed that half of the pelvic samples were dominated by a
      single organism while the other half exhibited a polymicrobial infection. The
      pelvic and cervical microbiota were similar in terms of both taxonomic richness
      and evenness. Pelvic microbiota was dominated by Acinetobacter, Escherichia,
      Sneathia and Streptococcus whereas cervical microbiota was dominated by
      Lactobacillus and Gardnerella. Only six pelvic samples were positive by culture
      diagnosis, three of which matched the NGS-based results. The PID group was
      further divided into 23 hydrosalpinx and 15 pyosalpinx samples according to the
      pelvic mass collected during surgery, the former showing a richer bacterial
      composition than the latter. CONCLUSION: The NGS-based method provides a more
      informative profile of pelvic microbiota than the culture method. The pelvic and
      cervical microbiota from the same patient were inconsistent with each other, and
      thus therapeutic decisions based on cervical microbiota may lead to antimicrobial
      misuse.

PMID- 30113306
TI  - Icelandic ovine Mycoplasma ovipneumoniae are variable bacteria that induce
      limited immune responses in vitro and in vivo.
AB  - PURPOSE: Mycoplasma ovipneumoniae is a pathogen that causes atypical pneumoniae
      in sheep and goats. While infection of lambs can induce strong immune responses,
      typically measured as serum antibodies, experimental vaccines appear to induce
      lower antibody titres. The purpose of this study was to better understand the
      bacterium and its interaction with the host, in order to improve the vaccination
      strategy. METHODOLOGY: We designed primers to compare seven M. ovipneumoniae gene
      sequences, in addition to the 16S sequence typically used, to estimate the
      variability between isolates. In addition, we labelled bacteria with a two-step
      process to examine whether bacteria could be intracellular as well as on the host
      surface in vitro. Finally, we vaccinated sheep four times and examined the
      induction of humoral and cellular responses. RESULTS: We were able to reliably
      amplify the seven housekeeping gene sequences to examine variability of the
      different isolates, and the bacteria could be found intracellularly, as well as
      on the host cell surface. Four vaccinations of sheep produced only modest humoral
      and cellular responses in this study, likely due to previous exposure of the
      animals to mycoplasmas. CONCLUSIONS: The moderate immune responses seen in this
      study indicate that previous exposure to mycoplasmas is a challenge for
      vaccination of lambs against M. ovipneumoniae. However, an alternative
      vaccination strategy, e.g. utilizing a recombinant vaccine, may overcome this
      vaccination hurdle in endemic regions and we suggest a possible vaccine
      candidate.

PMID- 30113307
TI  - Excess body weight and age associated with the carriage of fluoroquinolone and
      third-generation cephalosporin resistance genes in commensal Escherichia coli
      from a cohort of urban Vietnamese children.
AB  - PURPOSE: Antimicrobial-resistant bacterial infections in low- and middle-income
      countries (LMICs) are a well-established global health issue. We aimed to assess
      the prevalence of and epidemiological factors associated with the carriage of
      ciprofloxacin- and ceftriaxone-resistant Escherichia coli and associated
      resistance genes in a cohort of 498 healthy children residing in urban Vietnam.
      METHODOLOGY: We cultured rectal swabs onto MacConkey agar supplemented with
      resistant concentrations of ciprofloxacin and ceftriaxone. Additionally, we
      screened meta-E. coli populations by conventional PCR to detect plasmid-mediated
      quinolone resistance (PMQR)- and extended-spectrum beta-lactamase (ESBL)-encoding
      genes. We measured the associations between phenotypic/genotypic resistance and
      demographic characteristics using logistic regression.Results/Key findings.
      Ciprofloxacin- and ceftriaxone-resistant E. coli were cultured from the faecal
      samples of 67.7 % (337/498) and 80.3 % (400/498) of children, respectively. The
      prevalence of any associated resistance marker in the individual samples was 86.7
      % (432/498) for PMQR genes and 90.6 % (451/498) for beta-lactamase genes.
      Overweight children were significantly more likely to carry qnr genes than
      children with lower weight-for-height z-scores [odds ratios (OR): 1.24; 95 %
      confidence interval (CI): 10.5-1.48 for each unit increase in weight for height;
      P=0.01]. Additionally, younger children were significantly more likely to carry
      ESBL CTX-M genes than older children (OR: 0.97, 95 % CI: 0.94-0.99 for each
      additional year, P=0.01). CONCLUSION: The carriage of genotypic and phenotypic
      antimicrobial resistance is highly prevalent among E. coli in healthy children in
      the community in Vietnam. Future investigations on the carriage of antimicrobial
      resistant organisms in LMICs should focus on the progression of carriage from
      birth and structure of the microbiome in obesity.

PMID- 30113309
TI  - Arabidopsis formin 2 regulates cell-to-cell trafficking by capping and
      stabilizing actin filaments at plasmodesmata.
AB  - Here, we demonstrate that Arabidopsis thaliana Formin 2 (AtFH2) localizes to
      plasmodesmata (PD) through its transmembrane domain and is required for normal
      intercellular trafficking. Although loss-of-function atfh2 mutants have no overt
      developmental defect, PD's permeability and sensitivity to virus infection are
      increased in atfh2 plants. Interestingly, AtFH2 functions in a partially
      redundant manner with its closest homolog AtFH1, which also contains a PD
      localization signal. Strikingly, targeting of Class I formins to PD was also
      confirmed in rice, suggesting that the involvement of Class I formins in
      regulating actin dynamics at PD may be evolutionarily conserved in plants. In
      vitro biochemical analysis showed that AtFH2 fails to nucleate actin assembly but
      caps and stabilizes actin filaments. We also demonstrate that the interaction
      between AtFH2 and actin filaments is crucial for its function in vivo. These data
      allow us to propose that AtFH2 regulates PD's permeability by anchoring actin
      filaments to PD.

PMID- 30113308
TI  - Motoneuron Wnts regulate neuromuscular junction development.
AB  - The neuromuscular junction (NMJ) is a synapse between motoneurons and skeletal
      muscles to control motor behavior. Unlike extensively investigated postsynaptic
      differentiation, less is known about mechanisms of presynaptic assembly. Genetic
      evidence of Wnt in mammalian NMJ development was missing due to the existence of
      multiple Wnts and their receptors. We show when Wnt secretion is abolished from
      motoneurons by mutating the Wnt ligand secretion mediator (Wls) gene, mutant mice
      showed muscle weakness and neurotransmission impairment. NMJs were unstable with
      reduced synaptic junctional folds and fragmented AChR clusters. Nerve terminals
      were swollen; synaptic vesicles were fewer and mislocated. The presynaptic
      deficits occurred earlier than postsynaptic deficits. Intriguingly, these
      phenotypes were not observed when deleting Wls in muscles or Schwann cells. We
      identified Wnt7A and Wnt7B as major Wnts for nerve terminal development in rescue
      experiments. These observations demonstrate a necessary role of motoneuron Wnts
      in NMJ development, in particular presynaptic differentiation.

PMID- 30113310
TI  - Integrated externally and internally generated task predictions jointly guide
      cognitive control in prefrontal cortex.
AB  - Cognitive control proactively configures information processing to suit expected
      task demands. Predictions of forthcoming demand can be driven by explicit
      external cues or be generated internally, based on past experience (cognitive
      history). However, it is not known whether and how the brain reconciles these two
      sources of information to guide control. Pairing a probabilistic task-switching
      paradigm with computational modeling, we found that external and internally
      generated predictions jointly guide task preparation, with a bias for internal
      predictions. Using model-based neuroimaging, we then show that the two sources of
      task prediction are integrated in dorsolateral prefrontal cortex, and jointly
      inform a representation of the likelihood of a change in task demand, encoded in
      frontoparietal cortex. Upon task-stimulus onset, dorsomedial prefrontal cortex
      encoded the need for reactive task-set adjustment. These data reveal how the
      human brain integrates external cues and cognitive history to prepare for an
      upcoming task.

PMID- 30113312
TI  - An assessment of intra-individual variability in carotid artery longitudinal wall
      motion: recommendations for data acquisition.
AB  - OBJECTIVE: To assess the intra-individual variation in carotid artery
      longitudinal wall motion (CALM) in healthy adults in order to determine the
      amount of data required to generate a representative measurement of CALM.
      APPROACH: We conducted an analysis of 27 healthy men to determine whether
      calculation of resting individual CALM outcomes is dependent on the number of
      averaged heart cycles. CALM was assessed at rest, 1-2 cm proximal to the right
      carotid bifurcation during a breath hold and was segmented into three motion
      displacements: systolic anterograde CALM, systolic retrograde CALM, and diastolic
      CALM. A 2D measure of total carotid artery motion (RALength) was also determined
      from the longitudinal and radial displacements. Outcomes were averaged discretely
      using two, three, four, five, and six consecutive heart cycles to assess the
      impact of additional data on intra-individual coefficients of variation (CV%) and
      intra-class correlations (ICC). MAIN RESULTS: Calculated means were similar
      between all heart cycle averaging for CALM displacements (all P  >  0.05), though
      the two-heart cycle average of RALength (P  =  0.06) was reduced in comparison to
      all other averages. Averaging data from four heart cycles was sufficient to
      generate a plateau in the variability in resting CALM displacements, such that
      within-subject ICC values all reached  >0.90 and CV% were similar to previously
      reported day-to-day variability in healthy adults. SIGNIFICANCE: There is
      variability in beat-to-beat measures of CALM that should be considered when
      designing protocols for data collection and analysis. We suggest that four
      consecutive heart cycles should be averaged to generate representative resting
      CALM outcomes in humans. While indices of variability were reduced when assessing
      outcomes generated from two to four heart cycles, no further improvements were
      observed when more heart cycles were included, indicating that averaging more
      than four heart cycles is likely not required.

PMID- 30113311
TI  - The role of acquisition and quantification methods in myocardial blood flow
      estimability for myocardial perfusion imaging CT.
AB  - In this work, we clarified the role of acquisition parameters and quantification
      methods in myocardial blood flow (MBF) estimability for myocardial perfusion
      imaging using CT (MPI-CT). We used a physiologic model with a CT simulator to
      generate time-attenuation curves across a range of imaging conditions, i.e. tube
      current-time product, imaging duration, and temporal sampling, and physiologic
      conditions, i.e. MBF and arterial input function width. We assessed MBF
      estimability by precision (interquartile range of MBF estimates) and bias
      (difference between median MBF estimate and reference MBF) for multiple
      quantification methods. Methods included: six existing model-based deconvolution
      models, such as the plug-flow tissue uptake model (PTU), Fermi function model,
      and single-compartment model (SCM); two proposed robust physiologic models (RPM1,
      RPM2); model-independent singular value decomposition with Tikhonov
      regularization determined by the L-curve criterion (LSVD); and maximum upslope
      (MUP). Simulations show that MBF estimability is most affected by changes in
      imaging duration for model-based methods and by changes in tube current-time
      product and sampling interval for model-independent methods. Models with three
      parameters, i.e. RPM1, RPM2, and SCM, gave least biased and most precise MBF
      estimates. The average relative bias (precision) for RPM1, RPM2, and SCM was 
      ?11% (?10%) and the models produced high-quality MBF maps in CT simulated phantom
      data as well as in a porcine model of coronary artery stenosis. In terms of
      precision, the methods ranked best-to-worst are: RPM1  >  RPM2  >  Fermi  >  SCM 
      >  LSVD  >  MUP [Formula: see text] other methods. In terms of bias, the models
      ranked best-to-worst are: SCM  >  RPM2  >  RPM1  >  PTU  >  LSVD [Formula: see
      text] other methods. Models with four or more parameters, particularly five
      parameter models, had very poor precision (as much as 310% uncertainty) and/or
      significant bias (as much as 493%) and were sensitive to parameter
      initialization, thus suggesting the presence of multiple local minima. For
      improved estimates of MBF from MPI-CT, it is recommended to use reduced models
      that incorporate prior knowledge of physiology and contrast agent uptake, such as
      the proposed RPM1 and RPM2 models.

PMID- 30113313
TI  - CASToR: a generic data organization and processing code framework for multi-modal
      and multi-dimensional tomographic reconstruction.
AB  - In tomographic medical imaging (PET, SPECT, CT), differences in data acquisition
      and organization are a major hurdle for the development of tomographic
      reconstruction software. The implementation of a given reconstruction algorithm
      is usually limited to a specific set of conditions, depending on the modality,
      the purpose of the study, the input data, or on the characteristics of the
      reconstruction algorithm itself. It causes restricted or limited use of
      algorithms, differences in implementation, code duplication, impractical code
      development, and difficulties for comparing different methods. This work attempts
      to address these issues by proposing a unified and generic code framework for
      formatting, processing and reconstructing acquired multi-modal and multi
      dimensional data. The proposed iterative framework processes in the same way
      elements from list-mode (i.e. events) and histogrammed (i.e. sinogram or other
      bins) data sets. Each element is processed separately, which opens the way for
      highly parallel execution. A unique iterative algorithm engine makes use of
      generic core components corresponding to the main parts of the reconstruction
      process. Features that are specific to different modalities and algorithms are
      embedded into specific components inheriting from the generic abstract
      components. Temporal dimensions are taken into account in the core architecture.
      The framework is implemented in an open-source C++ parallel platform, called
      CASToR (customizable and advanced software for tomographic reconstruction).
      Performance assessments show that the time loss due to genericity remains
      acceptable, being one order of magnitude slower compared to a manufacturer's
      software optimized for computational efficiency for a given system geometry.
      Specific optimizations were made possible by the underlying data set organization
      and processing and allowed for an average speed-up factor ranging from 1.54 to
      3.07 when compared to more conventional implementations. Using parallel
      programming, an almost linear speed-up increase (factor of 0.85 times number of
      cores) was obtained in a realistic clinical PET setting. In conclusion, the
      proposed framework offers a substantial flexibility for the integration of new
      reconstruction algorithms while maintaining computation efficiency.

PMID- 30113314
TI  - Radiation interaction parameters of dosimetric importance for some commonly used
      compensators in IMRT using Monte Carlo simulation code.
AB  - Radiotherapy is one of the commonly used treatments for cancer. A compensator is
      a device used in intensity modulated radiotherapy (IMRT) treatments to compensate
      for the irregularities of the body. One can provide a more uniform distribution
      of dose for the treatment of tumors using compensators in IMRT to obtain a better
      therapeutic outcome. A variety of compensators are used in IMRT. One high Z
      (cerrobend), two medium Z (brass and steel) and one low Z (lucite) compensators
      are selected for the present study. The mass attenuation coefficients have been
      computed in an energy range of 15 keV to 15 MeV using XCOM program and the Monte
      Carlo N-particle-5 (MCNP5) code. The percentage deviation between the values
      indicates that the mass attenuation coefficients obtained using both the methods
      are in good agreement. These values are further used to calculate the linear
      attenuation coefficients, mass energy absorption coefficients, effective atomic
      numbers, electron densities, equivalent atomic numbers and energy absorption and
      exposure buildup factors. All these parameters have been calculated in the energy
      range of 0.015-15.0 MeV. The variation of parameters has been studied with
      incident photon energies, chemical composition and penetration depth of the
      various compensators. It is observed that up to 3 MeV and 14 mean free path
      (mfp): compensator with lowest values of the effective atomic numbers has the
      highest value of the buildup factor. Cerrobend has a particularly high value of
      the buildup factor near 100 keV. Above 3 MeV and 14 mfp: compensator with lowest
      values of the effective atomic numbers has the lowest value of the buildup
      factor. Thus a complete reversal in trend is observed at 3 MeV and 14 mfp. All
      these observation have been explained due to the dominance of the different
      interaction processes in different energy regions.

PMID- 30113315
TI  - The mechanical bidomain model of cardiac muscle with curving fibers.
AB  - In the heart, cardiac muscle fibers curve creating zones of membrane forces
      resulting in regions of mechanotransduction. This study uses the finite
      difference method to solve the mechanical bidomain equations numerically for a
      complex fiber geometry. The magnitude of the active tension T is constant but its
      direction makes an angle with the x-axis that varies with position. Differences
      between the intracellular and extracellular displacements result from the
      bidomain behavior of the tissue that gives rise to forces on the integrin
      proteins in the membrane. The long-term goal is to use the mechanical bidomain
      model to suggest experiments and make predictions about growth and remodeling in
      the heart.

PMID- 30113316
TI  - Nanodiamonds and gold nanoparticles to obtain a hybrid nanostructure with
      potential applications in biomedicine.
AB  - Using detonation nanodiamonds and fluorescent nitrogen-vacancy center
      nanodiamonds, linked to gold nanoparticles, we synthesized two hybrid
      nanostructures (HGDs) that were subsequently conjugated with a fluorophore. An
      amplification effect induced by the gold nanoparticles increased the emission
      spectrum of the fluorophore, maximizing the possibilities for imaging
      applications of these HGDs. The incubation of the nanostructures with HeLa cells
      produced no alteration of cell viability after 3 h and showed the presence of
      nanostructures in the cell cytoplasm at 24 h. These observations also indicate
      the potential biomedical use of the proposed HGDs.

PMID- 30113317
TI  - Physical activity characterization: does one site fit all?
AB  - BACKGROUND: It is evident that a growing number of studies advocate a wrist-worn
      accelerometer for the assessment of patterns of physical activity a priori, yet
      the veracity of this site rather than any other body-mounted location for its
      accuracy in classifying activity is hitherto unexplored. OBJECTIVE: The objective
      of this review was to identify the relative accuracy with which physical
      activities can be classified according to accelerometer site and analytical
      technique. METHODS: A search of electronic databases was conducted using Web of
      Science, PubMed and Google Scholar. This review included studies written in the
      English language, published between database inception and December 2017, which
      characterized physical activities using a single accelerometer and reported the
      accuracy of the technique. RESULTS: A total of 118 articles were initially
      retrieved. After duplicates were removed and the remaining articles screened, 32
      full-text articles were reviewed, resulting in the inclusion of 19 articles that
      met the eligibility criteria. CONCLUSION: There is no 'one site fits all'
      approach to the selection of accelerometer site location or analytical technique.
      Research design and focus should always inform the most suitable location of
      attachment, and should be driven by the type of activity being characterized.

PMID- 30113318
TI  - A unified computational framework for modeling genome-wide nucleosome landscape.
AB  - Nucleosomes form the fundamental building blocks of eukaryotic chromatin, and
      previous attempts to understand the principles governing their genome-wide
      distribution have spurred much interest and debate in biology. In particular, the
      precise role of DNA sequence in shaping local chromatin structure has been
      controversial. This paper rigorously quantifies the contribution of hitherto
      debated sequence features-including G+C content, 10.5 bp periodicity, and
      poly(dA:dT) tracts-to three distinct aspects of genome-wide nucleosome landscape:
      occupancy, translational positioning and rotational positioning. Our
      computational framework simultaneously learns nucleosome number and nucleosome
      positioning energy from genome-wide nucleosome maps. In contrast to other
      previous studies, our model can predict both in vitro and in vivo nucleosome maps
      in Saccharomyces cerevisiae. We find that although G+C content is the primary
      determinant of MNase-derived nucleosome occupancy, MNase digestion biases may
      substantially influence this GC dependence. By contrast, poly(dA:dT) tracts are
      seen to deter nucleosome formation, regardless of the experimental method used.
      We further show that the 10.5 bp nucleotide periodicity facilitates rotational
      but not translational positioning. Applying our method to in vivo nucleosome maps
      demonstrates that, for a subset of genes, the regularly-spaced nucleosome arrays
      observed around transcription start sites can be partially recapitulated by DNA
      sequence alone. Finally, in vivo nucleosome occupancy derived from MNase-seq
      experiments around transcription termination sites can be mostly explained by the
      genomic sequence. Implications of these results and potential extensions of the
      proposed computational framework are discussed.

PMID- 30113319
TI  - Opioid-related Emergency Department Visits and Hospitalizations Among
      Commercially Insured Individuals, 2009-2015.
AB  - OBJECTIVES: Overall opioid prescribing rates have decreased since 2012, but
      opioid-involved deaths have not. This study describes the regional and overall
      trends of opioid-related emergency department visits (EDVs) and hospitalizations
      of commercially insured patients on chronic opioids and those on concurrent
      opioids and benzodiazepines. METHODS: Secondary data analysis from Truven Health
      MarketScan Commercial Claims and Encounters (MarketScan) database from 2009 to
      2015 was used. Outcomes were geographic rates of opioid-related EDVs and
      hospitalizations and rates of concurrent benzodiazepine and opioid use. RESULTS:
      Rates of opioid-related EDVs and hospitalizations for patients on chronic opioids
      have decreased since 2009. Two thirds of those with opioid-related EDVs and
      nearly 3-quarters of those with an opioid-related hospitalization were
      coprescribed benzodiazepines. The North Central region had the highest proportion
      of individuals on chronic opioid therapy (2.7%) in 2015. However, the South had
      not only the highest rates of opioid-related EDVs (23/100,000 in 2015) and opioid
      related hospitalizations (39/100,000 in 2015) but also the largest percentage of
      individuals on concurrent opioids and benzodiazepines (41%). DISCUSSION: Rates of
      opioid-related EDVs and hospitalizations, as well as concurrent opioid and
      benzodiazepine use, vary geographically. More research is needed to examine
      factors that impact regional variation and what influences the concurrent use of
      opioids and benzodiazepines.

PMID- 30113320
TI  - Extracellular Mitochondrial DNA and N-Formyl Peptides in Trauma and Critical
      Illness: A Systematic Review.
AB  - OBJECTIVES: Extracellular mitochondrial DNA and N-formyl peptides released
      following tissue damage may contribute to systemic inflammation through
      stimulation of the innate immune system. In this review, we evaluate existing in
      vivo human data regarding a role for mitochondrial DNA and N-formyl peptides in
      producing systemic inflammation in trauma and critical illness, investigate the
      utility of these molecules in risk prediction and clinical decision support, and
      provide suggestions for standardization of future research. DATA SOURCES: PubMed,
      Embase (1971-2017). STUDY SELECTION: Studies measuring extracellular
      mitochondrial DNA and/or N-formyl peptides in acutely ill patients. DATA
      EXTRACTION: Fifty-four studies were analyzed. Data extracted included article
      characteristics, methods, results, and performance in clinical prediction. DATA
      SYNTHESIS: The most common patient types investigated were trauma (19 studies)
      and sepsis (eight). In studies comparing patient mitochondrial DNA or N-formyl
      peptide levels to healthy controls, 38 (90.5%) reported significantly elevated
      mitochondrial DNA levels in patients at first reported time point, as did the one
      study making this comparison for N-formyl peptides. Nine studies (81.8%) reported
      significantly elevated plasma/serum mitochondrial DNA levels in at least one time
      point in patients who developed inflammatory complications of their primary
      pathology compared with patients without inflammatory complications. For the
      ability of mitochondrial DNA to predict complications or outcomes, the area under
      the curve was 0.7 or greater in 84.6% of receiver operating characteristic
      curves, and 92.9% of odds, adjusted odds, risk, and hazard ratios were
      statistically significant. CONCLUSIONS: Extracellular mitochondrial DNA levels
      are elevated early in patients' hospital courses in many acute illnesses and are
      higher in patients who develop inflammatory complications. Elevated mitochondrial
      DNA levels may be clinically useful in risk prediction and clinical decision
      support systems. Further research is needed to determine the role of
      extracellular N-formyl peptides in systemic inflammation and their possible
      clinical utility.

PMID- 30113321
TI  - Optimizing outcome measurement with murine ferric chloride-induced thrombosis.
AB  - : The murine FeCl3 model is a widely used model for studying arterial thrombosis,
      yet provides limited information from each mouse, often only a single time point
      for the onset of occlusion (defined as the time to occlusion; TTO). To optimize
      data from the murine ferric chloride model of thrombosis. FeCl3 injury was
      induced in the carotid arteries of wild-type and Factor IX (FIX) knockout mice,
      with infusion of recombinant FIX (rFIX) to normalize FIX deficiency at various
      times around FeCl3 injury. The TTO was recorded as a percentage of baseline flow
      as occlusion continued to zero flow, with identification of reflow events. The
      TTO among the treatment groups of FIX-deficient mice showed no statistical
      differences, except with physiological saline-treated FIX-deficient mice and
      those receiving delayed treatment. Incidences of occlusion were 100% for wild
      type mice and FIX-deficient mice receiving slow infusions of rFIX at early times
      around the FeCl3 application. In contrast, only 68% of FIX-deficient mice
      achieved occlusion with preinfusion of rFIX and none occluded with delayed rFIX
      infusion. A majority of occluded vessels exhibited reflow events, with
      significantly lower incidence for slow infusion of rFIX starting 4 min after
      FeCl3 application in comparison with preinjury bolus, demonstrating
      characterization of a differential response to timing and infusion rates of
      treatment. Simple use of the time to occlusion may not maximize data available
      from the FeCl3 arterial thrombosis model. Inclusion of documenting reflow events
      can extend the useful data obtained with application of this model.

PMID- 30113322
TI  - Diagnosis of HIV-associated tuberculosis.
AB  - PURPOSE OF REVIEW: The current review highlights recent advances in tuberculosis
      (TB) diagnostics that are relevant for clinicians engaged in the care of HIV
      positive adults. RECENT FINDINGS: The first section focuses on newly available
      tools, highlighting recent progress. The second section focuses on new diagnostic
      approaches that are not yet widely available or implemented, but have
      considerable potential to improve the management of TB/HIV coinfected persons.
      The final section speculates about future directions that may be fruitful.
      SUMMARY: Advances in Mycobacterium tuberculosis nucleic acid amplification-based
      genotypic tests stand to improve case detection and drug susceptibility testing
      in the near term. Identification of human gene expression signatures that are
      associated with TB and/or TB risk, and the identification of novel M.
      tuberculosis targets coupled with exploitation of advances in biosensor
      technology may transform TB diagnosis in the future.

PMID- 30113324
TI  - Epidemiology of binge eating disorder.
AB  - PURPOSE OF REVIEW: In 2013, binge eating disorder (BED) was officially recognized
      as a distinct eating disorder in the Fifth Edition of the Diagnostic and
      Statistical Manual of Mental Disorders. The purpose of this review is to assess
      the available epidemiological data to determine whether BED should be considered
      for inclusion in global disease burden quantification efforts, such as the Global
      Burden of Disease Study (GBD). RECENT FINDINGS: A systematic search of three
      electronic databases (PubMed, EMBASE, and PsycINFO) found 32 studes meeting GBD
      inclusion criteria. The global pooled prevalence of BED was 0.9% (95% confidence
      intervals: 0.7-1.0%). Although women (1.4%, 1.1-1.7%) had higher prevalence than
      men (0.4%, 0.3-0.6%), no significant difference in prevalence was found between
      high-income countries (0.9%, 0.8-1.1%) and low- and middle-income countries
      (0.7%, 0.3-1.1%). SUMMARY: The current article presents the findings of a recent
      systematic review of the epidemiology of BED and discusses the case for including
      BED as a new cause in future iterations of GBD.

PMID- 30113323
TI  - Prevalence and Distribution of Diffuse Idiopathic Skeletal Hyperostosis on Whole
      spine Computed Tomography in Patients With Cervical Ossification of the Posterior
      Longitudinal Ligament: A Multicenter Study.
AB  - STUDY DESIGN: This was a retrospective multicenter study. OBJECTIVE: To clarify
      the progression of diffuse idiopathic skeletal hyperostosis (DISH) using whole
      spine computed tomography in patients with cervical ossification of the posterior
      longitudinal ligament (OPLL). SUMMARY OF BACKGROUND DATA: DISH and cervical OPLL
      frequently coexist, and can cause ankylosing spinal fractures due to
      biomechanical changes and fragility of the affected vertebrae. The epidemiology
      and pathophysiology of DISH occurring with cervical OPLL are unclear. MATERIALS
      AND METHODS: We used whole-spine computed tomography to determine the prevalence
      of DISH in 234 patients with a diagnosis of cervical OPLL based on plain cervical
      radiographs. We established a novel system for grading the progression of DISH
      based on a cluster analysis of the DISH distribution along the spine. We
      calculated the correlation coefficient between this grading system and patient
      age. RESULTS: The prevalence of DISH in patients with cervical OPLL was 48.7%.
      Patients with DISH were significantly older than those who did not have DISH
      (67.3 vs. 63.4 y; P=0.005). Cluster analysis classified the DISH distribution
      into 6 regions, based on the levels affected: C2-C5, C3-T1, C6-T5, T3-10, T8-L2,
      and T12-S1. DISH was observed most frequently at T3-T10. We defined a system for
      grading DISH progression based on the number of regions involved, from grade 0 to
      6. DISH was distributed at T3-T10 in >60% of the grade 1 patients, whereas most
      patients with DISH at the cervical or lumbar spine were grade 4 or 5. There was a
      weak but significant correlation between the DISH grade and patient age.
      CONCLUSIONS: DISH was present in nearly half of the patients with cervical OPLL.
      DISH was more common in older patients. DISH developed at the thoracic level and
      progressed into the cervical and/or lumbar spine with age. LEVEL OF EVIDENCE:
      Level III.

PMID- 30113326
TI  - Imported onchocerciasis in migrants and travelers.
AB  - PURPOSE OF REVIEW: With increasing international travel and mass global
      population migration, clinicians in nonendemic countries must be familiar with
      imported neglected tropical diseases including onchocerciasis, which is commonly
      known as 'river blindness'. RECENT FINDINGS: Imported onchocerciasis manifests
      differently in travelers compared with migrants from endemic areas and is likely
      underdiagnosed in both groups. Recent clinical studies confirm that eosinophilia
      is not a sensitive marker for Onchocerca volvulus, with one-third of patients
      having a normal eosinophil count. Novel diagnostics measuring antibodies to
      multiple recombinant O. volvulus antigens maintain a high sensitivity while
      improving specificity compared with conventional pan-filarial serologic testing.
      A 6-week course of doxycycline has macrofilaricidal activity through Wolbachia
      depletion and may be useful in nonendemic areas in addition to standard serial
      ivermectin. SUMMARY: Recent studies characterizing distinct clinical
      presentations in travelers and migrants may enable clinicians to better recognize
      imported onchocerciasis. Although novel diagnostics have improved specificity,
      most remain restricted to tropical disease reference laboratories and to date
      there is no marker of cure. Prolonged doxycycline treatment may reduce the need
      for serial ivermectin, though more potent short-course macrofilaricidal drugs are
      being developed.

PMID- 30113325
TI  - Relapse in anorexia nervosa: a systematic review and meta-analysis.
AB  - PURPOSE OF REVIEW: Relapse is common in patients with anorexia nervosa. The aim
      of this study is to systematically review the existing literature on relapse in
      anorexia nervosa. RECENT FINDINGS: A systematic literature search was conducted
      in PubMed, PsychInfo and CINAHL published up to April 2018. Of the 1527 studies
      screened, 16 studies were included in the present review. SUMMARY: This analysis
      shows that, of the patients included in this review, 31% relapsed after
      treatment. The highest risk of relapse is during the first year after discharge
      and this risk continues for up to 2 years. An overview was made of all factors
      significantly associated with a higher risk of relapse, resulting in the
      following four clusters: eating disorder variables, comorbidity symptoms, process
      treatment variables and demographic variables. Future research on relapse
      prevention is necessary to further unravel the mechanisms that might lead to
      relapse.

PMID- 30113328
TI  - Teaching dysmorphology in the era of genomics: new technologies, new learners.

PMID- 30113327
TI  - Recent developments in the epidemiology, diagnosis, and treatment of Fasciola
      infection.
AB  - PURPOSE OF REVIEW: This review aims at describing the latest research in Fasciola
      epidemiology, diagnosis, treatment, and control in endemic countries. RECENT
      FINDINGS: The geographic distribution and range of reservoirs for Fasciola
      hepatica continues to expand. The impact of fascioliasis goes beyond human
      disease to affect food security and income in developed and developing countries.
      Promising serologic and molecular methods to diagnose fascioliasis have been
      described, but are not widely available. Triclabendazole remains the only highly
      active medication to treat human and livestock infected with juvenile and adult
      forms of Fasciola spp. Efforts to control fascioliasis may be hindered by the
      emergence of resistance to triclabendazole among livestock and subsequently in
      humans. SUMMARY: Increased awareness and surveillance are likely to uncover the
      real distribution and burden of fascioliasis in human. Research into new drugs or
      adjuvants to tackle the emerging resistance to triclabendazole is imperative to
      treat and control Fasciola infection.

PMID- 30113329
TI  - Noninvasive measures in atopic dermatitis.
AB  - PURPOSE OF REVIEW: To summarize the current knowledge on the morphology,
      functionality and biochemical composition of the skin in allergic reactions. We
      address novel noninvasive techniques that promise to disclose intimate mechanisms
      of skin allergy in vivo. Epidermal barrier is not just a static wrap of the
      organism but rather a dynamic field for immunological, biophysical and
      biochemical processes and serves as a bio-sensor for exogenous danger signals.
      RECENT FINDINGS: Classical biophysical methods are amended by novel in-vivo
      techniques, such as Raman spectroscopy, analysing the skin microcomposition and
      develop epidermal profiles. Visualization techniques, such as reflectance
      spectroscopy and optical coherence tomography (OCT) are employed in studying the
      micro-morphological changes in the skin of allergic patients. SUMMARY: The
      noninvasive assessment of skin functions, micro-morphology and biochemical as
      well as immunological pathways will help to better understand skin allergies.
      They will allow to detect subtypes, for example in atopic dermatitis and to
      develop specific treatment modalities.

PMID- 30113331
TI  - To Drain or Not to Drain Infraperitoneal Anastomosis after Rectal Excision for
      Cancer: An Unclosed Debate.

PMID- 30113330
TI  - Ovarian conservation in management of pediatric gynecology malignancies.
AB  - PURPOSE OF REVIEW: The purpose of this review is to outline ovarian conservation
      and fertility sparing surgery (FSS) in the management of the most common
      pediatric gynecology malignancies. RECENT FINDINGS: Management of gynecologic
      malignancies has evolved to have a greater appreciation for adverse late effects
      from radical surgery, chemotherapy, and radiation. A growing body of literature
      has led to a paradigm shift toward ovarian conservation and FSS in the management
      of pediatric ovarian malignancies and genitourinary rhabdomyosarcoma (RMS). The
      role of minimally invasive surgery is still being explored but guidelines support
      this approach as a viable option for early stage ovarian cancers when performed
      by skilled surgeons. Research continues to address settings in which adjuvant
      chemotherapy for ovarian cancer can be avoided. Treatment for genitourinary RMS
      has transitioned from radical surgery to a conservative multimodal approach with
      FSS, systemic chemotherapy, and targeted radiation. SUMMARY: FSS and ovarian
      conservation are emerging concepts in the management of gynecologic malignancies
      in young women. Conservative surgical approaches and avoidance of gonadotoxic
      chemotherapy and radiation to minimize acute and long-term complications while
      maintaining efficacy are important considerations. Fertility preservation
      techniques continue to evolve and offer young women the opportunity for future
      fertility and preservation of ovarian function.

PMID- 30113332
TI  - Are Postoperative Components of ERAS the Real Major Factors for Optimal Recovey?

PMID- 30113333
TI  - The Virtual Hepatectomy Changed the Practice of Liver Surgery: More Details, More
      Significance.

PMID- 30113334
TI  - Defining Benchmarks for Transthoracic Esophagectomy: A Multicenter Analysis of
      Total Minimally Invasive Esophagectomy in Low-risk Patients.

PMID- 30113335
TI  - High Incidence and Clinical Significance of MYC Rearrangements in Primary
      Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type.
AB  - Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) and
      primary cutaneous follicle center lymphoma (PCFCL) are cutaneous B-cell lymphomas
      (CBCL) with different clinical characteristics and behavior. PCDLBCL-LT is the
      most aggressive CBCL with a relatively poor prognosis. In nodal diffuse large B
      cell lymphoma (DLBCL), rearrangements of the MYC gene, especially in combination
      with a second hit in BCL2 and/or BCL6, and double protein expression of MYC and
      BCL2 (DE) are adverse prognostic factors. As the clinical significance of these
      factors in CBCL is largely unknown, we studied the frequency and prognostic value
      of MYC rearrangements and DE in a cohort of 44 patients with PCDLBCL-LT and 17
      patients with PCFCL. Compared with nodal DLBCL (9% to 14%), the PCDLBCL-LT
      patients had a high incidence of MYC rearrangements (32%), but only 2 patients
      (4%) had a second hit, both with BCL6. PCDLBCL-LT patients with a MYC
      rearrangement showed an inferior disease-specific survival (Log-rank, P=0.036)
      and disease-free survival (Log-rank, P=0.028), but no significant adverse effect
      on overall survival (Log-rank, P=0.157) at 5 years compared with patients without
      a MYC rearrangement. DE, present in 65% of the PCDLBCL-LT patients, was not
      associated with reduced survival. In the PCFCL group, MYC rearrangements and DE
      were not detected. In conclusion, this study identifies a high incidence of MYC
      rearrangements in PCDLBCL-LT compared to nodal DLBCL and further shows that a MYC
      rearrangement is an inferior prognostic marker in these patients. Therefore, our
      data suggest that it is useful to perform MYC-FISH in all newly diagnosed PCDLBCL
      LT patients.

PMID- 30113336
TI  - Staphylococcus aureus in cystic fibrosis: pivotal role or bit part actor?
AB  - PURPOSE OF REVIEW: The cystic fibrosis (CF) lung has long been appreciated as a
      competitive niche for complex interactions between bacterial species. The
      individual relationships between effects on the host, and thereafter clinical
      outcomes, has been poorly understood. We aim to describe the role of Staphyloccus
      aureus, one of the most commonly encountered bacteria cultured from the
      respiratory tracts of people with CF, and it's complex interplay with other
      organisms, with particular attention to Pseudomonas aeruginosa. RECENT FINDINGS:
      We describe the challenges posed in understanding the role that S. aureus plays
      in the CF lung, including the difficulties in interpreting culture results
      depending upon sampling technique, relationships with P. aeruginosa and the rest
      of the microbiome, as well as discussing the relative merits and potential harms
      of antibiotic prophylaxis. Finally, we describe the particular challenge of
      methicillin-resistant S. aureus. SUMMARY: We describe research underway that will
      address the long-held contentious issues of antibiotic prophylaxis. We also
      describe the emerging research interest in determining whether, at differences
      phases in the evolution of CF airways infection, S. aureus infection can have
      both harmful and protective effects for the host.

PMID- 30113337
TI  - CORR Insights(r): 2018 Frank Stinchfield Award: Spinopelvic Hypermobility Is
      Associated With an Inferior Outcome After THA: Examining the Effect of Spinal
      Arthrodesis.

PMID- 30113338
TI  - Gendered Innovations in Orthopaedic Science: What's in a Name?

PMID- 30113339
TI  - CORR Insights(r): Higher Volume Surgeons Have Lower Medicare Payments,
      Readmissions, and Mortality After THA.

PMID- 30113340
TI  - Current Procedural Terminology Codes - Why Are They Important?

PMID- 30113341
TI  - Radiologic Evaluation of Clinically Benign Rectal Neoplasms May Not Be Necessary
      Before Local Excision.
AB  - BACKGROUND: Local excision may be curative for benign and malignant rectal
      neoplasms. Because many early rectal cancers are discovered incidentally after
      local excision of clinically benign lesions, it is unclear whether preoperative
      imaging with transrectal ultrasound or MRI affects management. OBJECTIVE: The
      purpose of this study was to determine the diagnostic characteristics and effect
      of preoperative imaging on the incidence of malignancy in benign rectal lesions
      undergoing local excision. DESIGN: Prospective data from 2 institutions were
      included. Coarsened exact matching created a balanced cohort comparing imaging
      and no-imaging groups. SETTING: The study was conducted at high-volume specialist
      referral hospitals. PATIENTS: Adult patients undergoing local excision via
      transanal endoscopic surgery between 1997 and 2016 for clinically benign rectal
      neoplasms were included. INTERVENTION: The study intervention included
      preoperative imaging with transrectal ultrasound and/or MRI. MAIN OUTCOME
      MEASURES: We measured the incidence of malignancy and diagnostic accuracy of
      preoperative imaging. RESULTS: A total of 620 patients were included (272 with
      preoperative imaging and 348 without). There were 250 patients undergoing
      transrectal ultrasound, and 24 patients undergoing MRI (2 patients underwent
      both). Transrectal ultrasound and MRI correctly identified malignant polyps in
      50% (11/22) and 44% (8/18). Overall agreement for benign versus malignant polyps
      between preoperative imaging and final pathology was kappa = 0.30 (95% CI, 0.18
      0.41) for transrectal ultrasound and 0.29 (95% CI, 0.01-0.57) for MRI. In both
      the overall and unmatched cohorts, the incidence of malignancy, margin
      involvement, and proportion of patients requiring salvage surgery was similar.
      LIMITATIONS: Data were obtained from 2 institutions with different equipment over
      a long time period. CONCLUSIONS: Preoperative imaging did not accurately identify
      malignancy in clinically benign rectal lesions and did not affect the incidence
      of malignancy, margin involvement, or proportion of patients requiring salvage
      surgery. Therefore, preoperative imaging may not be necessary for clinically
      benign lesions undergoing local excision. See Video Abstract at
      http://links.lww.com/DCR/A695.

PMID- 30113343
TI  - The Association Between Buccal Mucosa Thickness and Periimplant Bone Loss and
      Attachment Loss: A Cross-Sectional Study.
AB  - PURPOSE: The aim of this study was to assess if there is an association between
      buccal mucosa thickness and periimplant attachment loss after 1 year of function.
      MATERIALS AND METHODS: A total of 28 patients (14 periimplantitis implants and 14
      healthy implants) were included. The buccal mucosal thickness was assessed using
      K-files at 3 mm apical to the soft tissue margin of the implant. Probing depth,
      recession (REC), clinical attachment level (CAL), bleeding on probing, and
      radiographic bone loss on mesial and distal sites of the implant were recorded.
      RESULTS: The data showed that there was a statistically significant difference in
      midfacial REC between thin and thick buccal mucosa groups. However, the CAL was
      not statistically significant different between both groups. In addition, there
      was no statistically significant difference in mesial and distal bone loss
      between implants with thin and thick mucosa. CONCLUSION: When the midfacial soft
      tissue thickness was thin, the midfacial REC was greater and the CAL also tended
      to be higher. There was no association between buccal mucosa thickness and
      periimplant bone loss on mesial and distal sites of the implant after 1 year of
      function.

PMID- 30113342
TI  - Vulnerability to the Cardiovascular Effects of Ambient Heat in Six US Cities:
      Results from the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - BACKGROUND: With climate change, temperatures are increasing. Heat-associated
      health events disproportionately affect certain subpopulations. However, prior
      research has often lacked information on individual-level health and air
      conditioning and neighborhood stressors/protections. OBJECTIVES: To assess
      whether (1) heat (2-day mean temperature above local 75th percentiles) is
      associated with increased heart rate and decreased blood pressure, controlling
      for age, time, season, daily ozone, and daily particulate matter (PM2.5) and (2)
      associations differ by antihypertensive medication use, renal function, fasting
      glucose, emotional support, air conditioning ownership and use, normalized
      difference vegetation index, neighborhood safety, and residence- specific oxides
      of nitrogen and PM2.5. METHODS: Health and behavioral characteristics were
      obtained repeatedly on participants of the Multi-Ethnic Study of Atherosclerosis
      in six US sites (2000-2010). These were linked with airport temperature, air
      quality, and satellite- and survey-derived neighborhood characteristics. We used
      a fixed-effects design, regressing health outcomes on linear temperature splines
      with knots at the 75th percentiles, interaction terms for each characteristic,
      and adjustment for month of year, age, PM2.5, and ozone. RESULTS: Overall, heat
      was not associated with heart rate. However, for a 2 degrees C increase in heat,
      systolic blood pressure decreased by 1.1 mmHg (95% CI = -1.6, -0.6) and diastolic
      blood pressure by 0.3 mmHg (95% CI = -0.6, -0.1). Among nonusers of
      antihypertensive medications, heat-associated decreases in SBP were 2.1 mmHg
      greater among individuals with central air conditioning versus those without.
      Confidence intervals around the remaining modifiers were wide after multiple
      comparisons corrections or sensitivity analyses. CONCLUSIONS: Outdoor heat is
      associated with decreasing blood pressure, and cardiovascular vulnerability may
      vary primarily by ownership of central air conditioning.

PMID- 30113344
TI  - Intramedullary Nailing of Periarticular Fractures.
AB  - Plate fixation has historically been the preferred surgical treatment method for
      periarticular fractures of the lower extremity. This trend has stemmed from
      difficulties with fracture reduction and concerns of inadequate fixation with
      intramedullary implants. However, the body of literature on management of
      periarticular fractures of the lower extremities has expanded in recent years,
      indicating that intramedullary nailing of distal femur, proximal tibia, and
      distal tibia fractures may be the preferred method of treatment in some cases.
      Intramedullary nailing reliably leads to excellent outcomes when performed for
      appropriate indications and when potential difficulties are recognized and
      addressed.

PMID- 30113345
TI  - Management of the Failed Medial Unicompartmental Knee Arthroplasty.
AB  - With recent design modifications, proper patient selection, and sound surgical
      technique, medial unicompartmental knee arthroplasty has demonstrated long-term
      success in the management of degenerative joint disease. Nevertheless,
      complications do occur, most often aseptic loosening, tibial fracture,
      polyethylene wear, bearing dislocation, disease progression, infection, and
      unexplained pain. Some failures can be managed with retention of the implant,
      whereas others require revision to total knee arthroplasty (TKA), possibly
      including augments and stems. Although outcomes of unicompartmental knee
      arthroplasty may not match those of a primary TKA, they tend to exceed results of
      revision of a previous TKA.

PMID- 30113346
TI  - Minimally Invasive Plate Osteosynthesis of Humeral Shaft Fractures: Current State
      of the Art.
AB  - Most closed humeral shaft fractures can be successfully managed nonsurgically.
      However, fractures for which closed treatment is unsuccessful are stabilized
      using either plates or intramedullary nails. There are shortcomings associated
      with each technique, including the potential complications of nonunion,
      infection, shoulder pain, and radial nerve injury. Minimally invasive plate
      osteosynthesis (MIPO), an innovative alternative treatment, is gaining in
      popularity. This technique is based on the anterior humeral shaft providing a
      relatively safe surface for plate application, and limited open exposures
      proximally and distally allow percutaneous insertion of the necessary implant.
      More than 40 articles have been published regarding MIPO, and it compares
      favorably to other available forms of treatment with excellent functional
      outcomes and a lower rate of iatrogenic radial nerve injury. Larger randomized
      controlled trials comparing this method with other accepted techniques, including
      nonsurgical management, are necessary to better define the role of MIPO in the
      management of humeral shaft fractures.

PMID- 30113348
TI  - Reply to the Letter to the Editor: Internal Fixation of Osteoporotic Bone.

PMID- 30113347
TI  - Letter to the Editor: Internal Fixation of Osteoporotic Bone.

PMID- 30113349
TI  - Incidence and risk factors of pulmonary atelectasis in mechanically ventilated
      trauma patients in ICU: a prospective study.
AB  - AIM: The aim of the study was to obtain information about the incidence and risk
      factors for pulmonary atelectasis in mechanically ventilated patients in the
      trauma ICU (TMICU). Pulmonary atelectasis is a common complication leading to
      serious lung dysfunction in patients in the TMICU and early identification of
      patients at risk is important for their effective management. METHODS: All trauma
      patients admitted to the TMICU with mechanical ventilation for more than 1 day
      were included in a prospective 12-month study. Pulmonary atelectasis was
      diagnosed from chest radiographs by a critical care doctor and radiologist.
      RESULTS: A total of 405 trauma patients were identified and data from 338
      patients analyzed showing the incidence of pulmonary atelectasis to be 14%.
      Multivariate analysis revealed significant risk factors to be chest injury with
      an adjusted odds ratio (AOR) of 102.8, abdominal injury (AOR: 4.6), surgical
      intervention (AOR: 8.4), comorbidity (AOR: 13.7), Acute Physiology and Chronic
      Health Evaluation II score (APACHE II) of at least 15 (AOR: 4.8), sedation of at
      least 7 days (AOR: 7.5) and mechanical ventilation of at least 9 days (AOR:
      3.43). Patients with chronic pulmonary disease tended to have higher risk for
      pulmonary atelectasis (AOR: 8.8). Patients with pulmonary atelectasis had longer
      stays in TMICU (P < 0.001) and higher mortality (P = 0.013). CONCLUSION: The
      incidence of pulmonary atelectasis in TMICU in Thailand is comparable with that
      of the developed world. Pulmonary atelectasis is particularly associated with
      chest trauma, whereas abdominal injury, APACHE II of at least 15, surgery,
      comorbidity and prolonged mechanical ventilation are also significant risk
      factors. Early interventions to prevent or treat pulmonary atelectasis in these
      patients may improve outcome and shorten their stay in the TMICU and hospital.

PMID- 30113350
TI  - Low-dose ketamine infusion reduces postoperative hydromorphone requirements in
      opioid-tolerant patients following spinal fusion: A randomised controlled trial.
AB  - BACKGROUND: The current opioid epidemic highlights the urgent need for effective
      adjuvant therapies to complement postoperative opioid analgesia. Intra-operative
      ketamine infusion has been shown to reduce postoperative opioid consumption and
      improve pain control in opioid-tolerant patients after spinal fusion surgery. Its
      efficacy for opioid-naive patients, however, remains controversial. OBJECTIVE: We
      hypothesised that low-dose ketamine infusion after major spinal surgery reduces
      opioid requirements in opioid-tolerant patients, but not in opioid-naive
      patients. DESIGN: Randomised placebo-controlled study. SETTING: Single-centre,
      tertiary care hospital, November 2012 until November 2014. PATIENTS: A total of
      129 patients were classified as either opioid-tolerant (daily use of opioid
      medications during 2 weeks preceding the surgery) or opioid-naive group, then
      randomised to receive either ketamine or placebo; there were thus four groups of
      patients. All patients received intravenous hydromorphone patient-controlled
      analgesia postoperatively. INTERVENTION: Patients in the ketamine groups received
      a ketamine infusion (bolus 0.2 mg kg over 30 min followed by 0.12 mg kg h for 24
      h). Patients in the placebo groups received 0.9% saline. MAIN OUTCOME MEASURES:
      The primary outcome was opioid consumption during the first 24 h postoperatively.
      The secondary outcome was numerical pain scores during the first 24 h and central
      nervous system side effects. RESULTS: Postoperative hydromorphone consumption was
      significantly reduced in the opioid-tolerant ketamine group, compared with the
      opioid-tolerant placebo group [0.007 (95% CI 0.006 to 0.008) versus 0.011 (95% CI
      0.010 to 0.011) mg kg h, Bonferroni corrected P < 0.001]. There was no difference
      in hydromorphone use between the opioid-naive groups (0.004 and 0.005 mg kg h in
      the opioid-naive ketamine and placebo group, respectively, P = 0.118). Pain
      scores did not differ significantly between the opioid-tolerant ketamine group
      and the opioid-naive groups. There was no significant difference in side effects
      among groups. CONCLUSION: Postoperative low-dose ketamine infusion reduces opioid
      requirements for the first 24 h following spinal fusion surgery in opioid
      tolerant, but not in opioid-naive patients. TRIAL REGISTRATION: NCT03274453 with
      clinicaltrials.gov.

PMID- 30113351
TI  - Emergence delirium in children is related to epileptiform discharges during
      anaesthesia induction: An observational study.
AB  - BACKGROUND: Epileptiform discharges frequently occur in children during induction
      of anaesthesia. However, studies analysing the impact of epileptiform discharges
      on postoperative emergence delirium in children are still scarce. The aim of this
      study is to correlate the incidence of epileptiform activity during anaesthesia
      induction with the occurrence of emergence delirium during stay in the recovery
      room. OBJECTIVES: Prospective, observational cohort study in children 0.5 to 8
      years old undergoing planned surgery. Bifrontal electroencephalogram electrodes
      were placed before induction of anaesthesia. Visual electroencephalogram analysis
      was performed from start of anaesthetic agent administration until intubation
      with regard to epileptiform patterns: rhythmic polyspikes; periodic epileptiform
      discharges; delta with spikes; and suppression with spikes. Emergence delirium
      was assessed during stay in the recovery room using the Pediatric Assessment of
      Emergence Delirium Score. DESIGN: Prospective, observational cohort study.
      SETTING: University hospital - Germany/Berlin. Children were included between
      September 2015 and February 2017. PATIENTS: A total of 62 Children, aged 0.5 to 8
      years old undergoing planned surgery were included. MAIN OUTCOME MEASURES:
      Primary outcome was emergence delirium. Secondary outcomes, peri-operative
      Electroencephalography (EEG) data analysis. The presented study analysed an
      association between emergence delirium and the occurrence of epileptiform
      discharges during anaesthesia induction. RESULTS: A total of 43.5% of the
      children developed emergence delirium and 56.5% did not. Epileptiform discharges
      were observed more often in children developing emergence delirium (63%) compared
      with children not developing emergence delirium (43%). But only the occurrence of
      interictal spike events - such as rhythmic polyspikes; periodic epileptiform
      discharges and delta with spikes - were significantly related to emergence
      delirium (emergence delirium-group 48% vs. nonemergence delirium-group 14%, OR =
      5.6 [95% CI: 1.7 to 18.7]; P = 0.004). CONCLUSION: Emergence delirium in children
      is significantly related to interictal spike events occurring during induction of
      anaesthesia. CLINICAL TRIAL: NCT02481999.

PMID- 30113352
TI  - Can We Improve Physical Health Monitoring for Patients Taking Antipsychotics on a
      Mental Health Inpatient Unit?
AB  - BACKGROUND: Patients with severe mental illness are at risk of medical
      complications, including cardiovascular disease, metabolic syndrome, and
      diabetes. Given this vulnerability, combined with metabolic risks of
      antipsychotics, physical health monitoring is critical. Inpatient admission is an
      opportunity to screen for medical comorbidities. Our objective was to improve the
      rates of physical health monitoring on an inpatient psychiatry unit through
      implementation of an electronic standardized order set. METHODS: Using a clinical
      audit tool, we completed a baseline retrospective audit (96 eligible charts) of
      patients aged 18 to 100 years, discharged between January and March 2012,
      prescribed an antipsychotic for 3 or more days. We then developed and implemented
      a standard electronic admission order set and provided training to inpatient
      clinical staff. We completed a second chart audit of patients discharged between
      January and March 2016 (190 eligible charts) to measure improvement in physical
      health monitoring and intervention rates for abnormal results. RESULTS: In the
      2012 audit, thyroid-stimulating hormone (TSH), blood pressure, blood glucose,
      fasting lipids, electrocardiogram (ECG), and height/weight were measured in 71%,
      92%, 31%, 36%, 51%, and 75% of patients, respectively. In the 2016 audit, TSH,
      blood pressure, blood glucose, fasting lipids, ECG, and height/weight were
      measured in 86%, 96%, 96%, 64%, 87%, and 71% of patients, respectively. There
      were statistically significant improvements (P < 0.05) in monitoring rates for
      blood glucose, lipids, ECG, and TSH. Intervention rates for abnormal blood
      glucose and/or lipids (feedback to family doctor and/or patient, consultation to
      hospitalist, endocrinology, and/or dietician) did not change between 2012 and
      2016. CONCLUSIONS: Electronic standardized order set can be used as a tool to
      improve screening for physical health comorbidity in patients with severe mental
      illness receiving antipsychotic medications.

PMID- 30113353
TI  - Psychopharmacology in Japan: An Overview and Recent Topics.

PMID- 30113354
TI  - The Role of C-Reactive Protein in Early Detection of Myocarditis Associated With
      Clozapine.

PMID- 30113355
TI  - In Vitro Mesenchymal Progenitor Cell Expansion is a Predictor of Transplant
      related Mortality and acute GvHD III-IV After Bone Marrow Transplantation in
      Univariate Analysis: A Large Single-Center Experience.
AB  - Mesenchymal stromal cells (MSCs) are multipotent stem cells able to differentiate
      into mesenchymal origin tissue and support the growth of hematopoietic stem
      cells. In order to understand the role of MSCs infused in bone marrow grafts, 53
      consecutive patients were analyzed for engraftment, acute and chronic graft
      versus-host disease (GvHD), transplant-related mortality (TRM), relapse
      incidence, and overall survival. The MSC content was measured as MSC expansion at
      the second passage. When in vitro-expanded MSC (cumulative population doubling at
      second passage, cPDp2) values were stratified according to the median value (2.2
      fold increase), the univariate analysis showed a significant difference in TRM
      (23% vs. 3.8%, P=0.05.) and in acute GvHD III-IV incidence (12% vs. 4%, P=0.04),
      while the multivariate analysis did not confirm its independent role. No clinical
      parameters in donors and recipients were identified as predictors of cPDp2
      expansion. Our study suggests a role for short-term ex vivo-expanded MSCs in
      reduced aGVHD III-IV incidence and TRM in univariate analysis. A multicenter,
      larger study is warranted to confirm these data.

PMID- 30113357
TI  - Risk Factors and the Prevention of Weight Gain During Induction Chemotherapy in
      Children With Acute Lymphoblastic.

PMID- 30113356
TI  - Paratesticular Fibrous Pseudotumor in Children: A Case Report and Review of
      Literature.
AB  - BACKGROUND: Paratesticular fibrous pseudotumor (PFP) is a rare benign tumor that
      can mimic malignant tumors; thus, radical orchiectomy was the standard treatment
      in the past. OBSERVATION: A 15-year-old boy came to our attention for a hard
      right inguinal swelling. An ultrasound showed a highly vascularized mass. The boy
      underwent a gonadal-sparing excision of the mass that was diagnosed to be a PFP.
      The patient recovered well, without recurrences at the follow-up. CONCLUSIONS:
      PFP is mostly asymptomatic, and its diagnosis is incidental. Only further 4
      pediatric cases were reported in the literature. Our case confirms that gonadal
      sparing surgery is an optimal treatment.

PMID- 30113358
TI  - Global Health Education at Home: Canadian Medical Students' Perspectives After
      Learning Alongside Haitian Peers.
AB  - PURPOSE: To explore how host medical students learn from visiting foreign
      students, by reporting on a global health program that has invited two or three
      Haitian medical students each year since 2013 to a Canadian medical school for a
      summer anatomy program. METHOD: In 2017, the authors conducted a qualitative
      descriptive study that collected data through one-on-one, semistructured
      interviews with 10 Canadian students, who participated in the Universite
      Quisqueya-McGill University collaborative, a bidirectional global health
      education initiative, 2013-2016. The authors' critical constructivist thematic
      analysis, while exploratory, was sensitized by their knowledge of contemporary
      frameworks of global health competencies, a postcolonial understanding of power
      relations, and three key concepts (agency, cultural humility, and reflexivity).
      RESULTS: The authors found two phenomena related to bidirectional exchange: the
      nature of the relationship between Canadian and Haitian students, and elements of
      the learning experience that facilitated transformation and growth. There were
      three important components to the nature of the relationship between Canadian and
      Haitian students-reflection on practices and privilege, negotiation of power
      dynamics, and perception of Haitian students as agents-and three components of
      the learning experience that facilitated transformation and growth-working in
      groups, common learning objectives, and informal social gatherings. CONCLUSIONS:
      Bidirectional programs may have implications for Canadian students' perception of
      the agency of international medical learners and may prompt self-reflection that
      manifests in a range of ways, including an experience of culture shock at home.
      These tensions seemed to create space to practice reflexivity and cultural
      humility.

PMID- 30113359
TI  - Core Clerkship Grading: The Illusion of Objectivity.
AB  - Core clerkship grading creates multiple challenges that produce high stress for
      medical students, interfere with learning, and create inequitable learning
      environments. Students and faculty alike succumb to the illusion of objectivity -
      that quantitative ratings converted to grades convey accurate measures of the
      complexity of clinical performance.Clerkship grading is the first high-stakes
      assessment within medical school and occurs just as students are newly immersed
      full time in an environment in which patient care supersedes their needs as
      learners. Students earning high marks situate themselves to earn entry into
      competitive residency programs and selective specialties. However, there is no
      commonly accepted standard for how to assign clerkship grades, and the process is
      vulnerable to imprecision and bias. Rewarding learners for the speed with which
      they adapt inherently favors students who bring advantages acquired before
      medical school and discounts the goal of all learners achieving competence.The
      authors propose that, rather than focusing on assigning core clerkship grades,
      assessment of student performance should incorporate expert judgment of learning
      progress. Competency-based medical education is predicated on the articulation of
      stepwise expectations for learners, with the support and time allocated for each
      learner to meet those expectations. Concurrently, students should ideally review
      their own performance data with coaches to self-assess areas of relative strength
      and areas for further growth. Eliminating grades in favor of competency-based
      assessment for learning holds promise to engage learners in developing essential
      patient care and teamwork skills and to foster their development of lifelong
      learning habits.

PMID- 30113360
TI  - Professional Responsibilities and Personal Impacts: Residents' Experiences as
      Participants in Education Research.
AB  - PURPOSE: Although the field of medical education research is growing and
      residents are increasingly recruited to participate as subjects in research
      studies, little is known about their experiences. The goal of this study was to
      explore the experiences and perceptions of residents who are study participants
      in medical education research. METHOD: A phenomenographic approach was chosen to
      examine the range of residents' experiences as research participants. A maximum
      variation sampling strategy was used to identify residents with diverse
      experiences. Semi-structured interviews that explored experiences as research
      participants were conducted with nineteen residents in internal medicine, general
      surgery, and pediatrics at the University of Toronto in 2015-2016. RESULTS: The
      perceptions and experiences of participants fell into two categories. First,
      participation was seen as a professional responsibility to advance the
      profession, including a desire to improve future educational practices and a
      sense of responsibility to contribute to the academic cause. Second, the
      experience was noted for its personal impact, including benefits (e.g., receiving
      monetary incentives or novel educational experiences) and risks (e.g., coercion
      and breaches of confidentiality). The time required to participate in a study was
      identified as one of the most important factors affecting willingness to
      participate and the impact of participation. CONCLUSIONS: Being a participant in
      medical education research can be perceived in different ways. Understanding the
      view of resident participants is important to optimize potential benefits and
      minimize risks and negative consequences for them, thus fostering ready
      participation and high-quality research.

PMID- 30113361
TI  - Governance of Academic Health Centers and Systems: A Conceptual Framework for
      Analysis.
AB  - Health care has evolved from a cottage industry to a very complex one comprising
      nearly one-fifth of the U.S. economy. Large aggregated health care systems have
      evolved primarily for the purpose of optimizing financial performance by
      capturing greater market share and taking advantage of economies of scale in care
      delivery. With the noble intent of providing a broader base of support for the
      academic mission, academic health centers (AHCs) have followed suit by partnering
      with community hospitals and organizations with variable prior experience in the
      education and research arenas. Such a strategy makes good business sense, but it
      creates challenges for the academic mission. Singular emphasis on physicians'
      clinical productivity enhances financial margin but often reduces faculty time
      and effort dedicated to the academic mission. While individual AHC governance is
      varied, the leadership structure of large aggregated health systems built around
      an AHC is even more complex and heterogeneous. Yet, to ensure the prosperity of
      the academic mission, the governance structure of such health care systems is of
      critical importance. Preservation of academic oversight of the faculty practice
      plan, a unifying central focal point of organizational decision-making, and
      genuine physician leadership are three overarching governance characteristics
      that strengthen the prosperity of the academic mission within large aggregated
      health systems. Despite the heterogeneous nature of academic health system
      governance, these critical components of organizational leadership structure
      facilitate support of a robust academic mission. Understanding these principles
      and objectives of governance is essential for critical faculty engagement in AHC
      leadership activities.

PMID- 30113362
TI  - Choosing Our Own Pathway to Competency-Based Undergraduate Medical Education.
AB  - After many years in the making, an increasing number of postgraduate medical
      education (PGME) training programs in North America are now adopting a competency
      based medical education (CBME) framework based upon entrustable professional
      activities (EPAs) that, in turn, encompass a larger number of competencies and
      training milestones. Following the lead of PGME, CBME is now being incorporated
      into undergraduate medical education (UME) in an attempt to improve integration
      across the medical education continuum and to facilitate a smooth transition from
      clerkship to residency by ensuring that all graduates are ready for indirect
      supervision of required EPAs on day one of residency training. The Association of
      Faculties of Medicine of Canada recently finalized its list of 12 EPAs, which
      closely parallels the list of 13 EPAs published earlier by the Association of
      American Medical Colleges, and defines the "core" EPAs that are an expectation of
      all medical school graduates.In this article, the authors focus on important,
      practical considerations for the transition to CBME that they feel have not been
      adequately addressed in the existing literature. They suggest that the transition
      to CBME should not threaten diversity in UME or require a major curricular
      upheaval. However, each UME program must make important decisions that will
      define its version of CBME, including which terminology to use when describing
      the construct being evaluated; which rating tools and raters to include in the
      assessment program; and how to make promotion decisions based upon all of the
      available data on EPAs.

PMID- 30113363
TI  - Ethical Shades of Gray: International Frequency of Scientific Misconduct and
      Questionable Research Practices in Health Professions Education.
AB  - PURPOSE: To maintain scientific integrity and engender public confidence,
      research must be conducted responsibly. Whereas deliberate scientific misconduct
      such as data fabrication is clearly unethical, other behaviors-often referred to
      as questionable research practices (QRPs)-exploit the ethical shades of gray that
      color acceptable practice. This study aimed to measure the frequency of self
      reported misconduct and QRPs in a diverse, international sample of health
      professions education (HPE) researchers. METHOD: In 2017, the authors conducted
      an anonymous, cross-sectional survey study. The web-based survey contained 43
      items that asked respondents to rate how often they had engaged in a variety of
      irresponsible research behaviors. The items were adapted from previously
      published surveys. RESULTS: In total, 590 HPE researchers took the survey. The
      mean age was 46 years (SD = 11.6), and the majority of participants were from the
      United States (26.4%), Europe (23.2%), and Canada (15.3%). The three most
      frequently reported irresponsible research behaviors were adding authors who did
      not qualify for authorship (60.6%), citing articles that were not read (49.5%),
      and selectively citing papers to please editors or reviewers (49.4%).
      Additionally, respondents reported misrepresenting a participant's words (6.7%),
      plagiarizing (5.5%), inappropriately modifying results (5.3%), deleting data
      without disclosure (3.4%), and fabricating data (2.4%). Overall, 533 (90.3%)
      respondents reported at least one irresponsible behavior. CONCLUSIONS:
      Notwithstanding the methodological limitations of survey research, these findings
      indicate that a substantial proportion of HPE researchers report a range of
      misconduct and QRPs. Consequently, reforms may be needed to improve the conduct
      of HPE research.Written work prepared by employees of the Federal Government as
      part of their official duties is, under the U.S. Copyright Act, a "work of the
      United States Government" for which copyright protection under Title 17 of the
      United States Code is not available. As such, copyright does not extend to the
      contributions of employees of the Federal Government.

PMID- 30113364
TI  - Using Machine Learning to Assess Physician Competence: A Systematic Review.
AB  - PURPOSE: To identify the different machine learning (ML) techniques that have
      been applied to automate physician competence assessment and evaluate how these
      techniques can be used to assess different competence domains in several medical
      specialties. METHOD: In May 2017, MEDLINE, EMBASE, PsycINFO, Web of Science, ACM
      Digital Library, IEEE Xplore Digital Library, PROSPERO, and Cochrane Database of
      Systematic Reviews were searched for articles published from inception to April
      30, 2017. Studies were included if they applied at least one ML technique to
      assess medical students', residents', fellows', or attending physicians'
      competence. Information on sample size, participants, study setting and design,
      medical specialty, ML techniques, competence domains, outcomes, and
      methodological quality was extracted. MERSQI was used to evaluate quality, and a
      qualitative narrative synthesis of the medical specialties, ML techniques, and
      competence domains was conducted. RESULTS: Of 4,953 initial articles, 69 met
      inclusion criteria. General surgery (24, 34.8%) and radiology (15, 21.7%) were
      the most studied specialties; natural language processing (24, 34.8%), support
      vector machine (15, 21.7%), and hidden Markov models (14, 20.3%) were the ML
      techniques most often applied; and patient care (63, 91.3%) and medical knowledge
      (45, 65.2%) were the most assessed competence domains. CONCLUSIONS: A growing
      number of studies have attempted to apply ML techniques to physician competence
      assessment. Although many studies have investigated the feasibility of certain
      techniques, more validation research is needed. The use of ML techniques may have
      the potential to integrate and analyze pragmatic information that could be used
      in real-time assessments and interventions.

PMID- 30113365
TI  - Becoming a Clinical Teacher: Identity Formation in Context.
AB  - PURPOSE: Most clinical teachers have not been trained to teach, and faculty
      development for clinical teachers is undermined by poor attendance, inadequate
      knowledge transfer, and unsustainability. A crucial question for faculty
      developers to consider is how clinicians become teachers "on the job." Such
      knowledge is important in the design of future workplace-based faculty
      development initiatives. The authors conducted a scoping review of research on
      the relationship between becoming a clinical teacher and the clinical
      environments in which those teachers work. METHOD: In June 2017, using the
      scoping review design described by Levac et al (2010), the authors searched
      twelve databases. They subjected the articles discovered to four phases of
      screening, using iteratively developed inclusion/exclusion criteria. They charted
      data from the final selection of articles and used thematic analysis to
      synthesize findings. RESULTS: Thirty-four research reports met the inclusion
      criteria. Most (n = 24) took an individualist stance towards identity, focusing
      on how teachers individually construct their teacher identity in tension with
      their clinician identities. Only 10 studies conceptualized clinical teacher
      identity formation as a social relational phenomenon, negotiated within
      hierarchical social structures. Twenty-nine of the included studies made little
      or no use of explicit theoretical frameworks, which limited their rigour and
      transferability. CONCLUSIONS: Clinicians reconciled their identities as teachers
      with their identities as clinicians by juggling the two, finding mutuality
      between them, or forging merged identities that minimized tensions between
      educational and clinical roles. They did so in hierarchical social settings where
      patient care and research were prioritized above teaching.

PMID- 30113366
TI  - Developing a Quality Measurement Strategy in an Academic Primary Care Setting: An
      Environmental Scan.
AB  - PURPOSE: The purpose of this project was to: (1) develop a strategy for primary
      care quality measurement using an environmental scan and interviews to identify
      best practices and candidate measures; (2) present recommendations to facilitate
      successful measurement. METHODS: Following stakeholder interviews and review of
      existing measures, we created a three-tiered recommendation system for selecting
      and implementing measures. We also developed a framework for reviewing and
      prioritizing measures and prepared a detailed project report. RESULTS: Interviews
      provided a broader perspective on measuring quality, including implementing
      measures, measuring value, and identifying measurement gaps. Our recommendations
      fall into three tiers: Tier 1 measures can be implemented quickly and include
      clinical processes and outcomes for preventive care and disease states. Tier 2
      measures require modifications to electronic health record, workflows, and/or
      staff preparation. Tier 3 (Strategic Vision) addresses topics that should be
      incorporated in the future to ensure high-quality primary care (adherence,
      patient activation, patient experience, teamness, staff satisfaction, and value),
      and infrastructure development to support ongoing quality measurement.
      CONCLUSIONS: Implementing a quality measurement strategy is challenging and labor
      intensive but is necessary to improve healthcare quality. Our work demonstrates
      the effort and investment required to progress quality measurement and offers
      recommendations for successfully undertaking this type of endeavor.

PMID- 30113367
TI  - Nonalcoholic fatty liver disease: current concepts, epidemiology and management
      strategies.
AB  - Nonalcoholic fatty liver disease (NAFLD) is now the most prevalent liver disease
      in the world. It involves a spectrum of conditions from hepatic steatosis to
      nonalcoholic steatohepatitis and liver fibrosis, and is a major cause of
      cirrhosis and hepatocellular carcinoma. It is defined by presence of steatosis in
      5% of hepatocytes or more in the absence of other causes of fatty liver. The
      metabolic syndrome is the major known risk factor for NAFLD. Dietary contributors
      such as high fructose intake and coffee consumption appear to increase and
      decrease the risk of disease respectively, but these links are unclear. Genetic
      associations have also been identified. The estimated prevalence of the disease
      varies according to diagnostic method and population demographics. It appears to
      be a major issue in Europe with population studies showing up to 50% of the
      individuals are affected while in the USA one in three adults are estimated to
      have NAFLD. Laboratory investigations and ultrasound are typically first-line
      investigations. Fibrosis may be assessed noninvasively through transient
      elastography and biomarkers but liver biopsy remains the gold standard to
      quantify hepatic damage. Associated comorbidities include cardiovascular disease
      and chronic kidney disease. Weight loss, dietary changes and exercise are
      recommended in management. Medications should be considered to manage underlying
      risk factors including insulin resistance. Surgical options include bariatric
      procedures and liver transplantation. The combination of rising prevalence and
      significant potential complications warrant further research into NAFLD,
      particularly in areas with research gaps including Eastern Europe.

PMID- 30113368
TI  - Alternatively spliced tissue factor levels are elevated in the plasma of patients
      with chronic liver diseases.
AB  - OBJECTIVES: In patients with chronic liver diseases, hypercoagulability can
      contribute to the progression of fibrosis and complications of cirrhosis. Tissue
      factor (TF) is a transmembrane glycoprotein that initiates the extrinsic pathway
      of blood coagulation. Recent investigations have established that TF is elevated
      in patients with pancreatic cancer, blood disorders, diabetes, and cardiovascular
      disease. Alternatively spliced tissue factor (asTF), a secreted form of TF,
      induces angiogenesis and exhibits low-level procoagulant activity. The aim of
      this study was to investigate whether the circulating levels of asTF are elevated
      in the plasma of patients with liver disease. MATERIALS AND METHODS: In a single
      center study, we retrospectively analyzed asTF plasma levels in healthy
      participants and patients having stage F0-F3 liver fibrosis, liver cirrhosis, as
      well as hepatocellular carcinoma (HCC). AsTF plasma levels were measured using a
      sandwich enzyme-linked immunosorbent assay. Values were expressed as median with
      interquartile range (IQR). RESULTS: The lowest median plasma asTF concentration
      (94 pg/ml, IQR: 33-275) was found in the healthy control group. The patients with
      low-grade liver fibrosis (F0-F1 group) displayed the highest median asTF
      concentration (404 pg/ml, IQR: 277-789). Significant differences between the asTF
      levels in the plasma of healthy participants and those in patients with grade F0
      F1 fibrosis (P<0.001), patients with grade F2-F3 fibrosis (P=0.019), patients
      with cirrhosis (P=0.004), and patients with HCC (P<0.001) were found using a
      Wilcoxon rank-sum test. Treatment-naive patients with HCC had significantly
      higher asTF levels (P=0.018) than those receiving treatment. AsTF levels were
      found to increase with worsening Child-Pugh scores and heightened liver disease
      activity. CONCLUSION: AsTF levels are elevated in patients with chronic liver
      diseases, which increase with worsening Child-Pugh scores and decrease following
      HCC therapy.

PMID- 30113369
TI  - Clinical and pathological profile of eosinophilic gastroenteritis.
AB  - BACKGROUND: Eosinophilic gastroenteritis (EoGE) can be diagnosed on the basis of
      histologic criteria; however, the pathology is considered to be heterogeneous.
      There is no consensus on the management of this enigmatic disorder with an
      unknown etiology. PATIENTS AND METHODS: Data for patients diagnosed with EoGE and
      followed up over a 1-year period were analyzed. Their symptoms, patterns of
      flares, and type of treatment were documented. The shift in peripheral blood
      eosinophil levels was also examined. RESULTS: A total of 10 (mean age, 44 years;
      range: 31-70 years; women, 5) patients were diagnosed with EoGE. The most
      frequent presenting symptom was abdominal pain, and eight patients were
      classified with mucosal type of EoGE. Chronic disease or multiple flares were
      observed in seven out of 10 (70.0%) patients, and all of them had a history of
      allergy. Four were corticosteroid dependent (three relapsed during corticosteroid
      tapering and one following corticosteroid withdrawal). One of them received anti
      IL5 monoclonal antibody that enabled corticosteroid dose tapering. In four
      patients with highly elevated initial eosinophil levels at diagnosis, the
      peripheral eosinophil level correlated with the amelioration and deterioration of
      their symptoms. The remaining three patients had a single flare without relapse.
      Two had no history of allergy. CONCLUSION: EoGE is a unique disorder with a
      variable clinical course. Although further studies are required to confirm our
      observations, the presence of other allergic disorders is associated with
      chronicity or multiple flares. Peripheral eosinophil level may be an effective
      biomarker for recurrence in patients with severe systemic disorders at diagnosis.

PMID- 30113372
TI  - SOS Asynchronies: Do We Need Help?

PMID- 30113370
TI  - Translational Sepsis Research: Spanning the Divide.
AB  - OBJECTIVE: Our knowledge of the molecular mechanisms of sepsis has attained
      exponential growth. Yet, the pillars of its care remain antibiotics, fluid
      resuscitation, and physiologic support of failing organ systems. The inability to
      bring biologic breakthroughs to the bedside is not for lack of effort. Over 60
      clinical trials of novel therapies, each heavily supported by the momentum of
      biologic data suggesting clinical utility, have been conducted and have failed to
      identify benefit. This mass of "negative" clinical data abut an equally towering
      mound of knowledge of sepsis biology, which collectively have led investigators
      to ask, "what happened?" DATA SOURCES: Review of published scientific literature
      via MEDLINE searches using key terms related to the article topics. STUDY
      SELECTION: Original articles, review articles, and systematic reviews were
      considered. DATA EXTRACTION: Articles were selected for inclusion based upon
      author consensus. DATA SYNTHESIS: Here, we present a synthetic review of some of
      the challenges in translating experimental animal models of sepsis to the
      bedside. We commence with the concept that the heterogeneity in the kinetics of
      the sepsis response serves as an important, often underappreciated but
      surmountable, source of translational impedance. Upon this groundwork, we discuss
      distinctions between animal experimentation and clinical trial design in the
      elements for hypothesis testing: cohort selection, power and sample size,
      randomization and blinding, and timing of intervention. From this concept, we
      develop a contextual framework for advancing the paradigm of animal-based
      investigations to facilitate science that transitions from molecule to medicine.
      CONCLUSIONS: A persistent divide exists between the laboratory and clinical
      research arenas, which may be addressable via systematic targeting of identified
      translational gaps.

PMID- 30113374
TI  - Progress Toward "Ruling Out" Sepsis.

PMID- 30113371
TI  - Executive Summary: Clinical Practice Guidelines for the Prevention and Management
      of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult
      Patients in the ICU.

PMID- 30113373
TI  - The Evolution of Post Intensive Care Syndrome.

PMID- 30113375
TI  - Music Therapy in Critical Illness: Entertainment With Benefits....

PMID- 30113376
TI  - Exposing and Engaging Unknown Unknowns in Traumatic Brain Injury.

PMID- 30113377
TI  - On Benzodiazepines, Paradoxical Agitation, Hyperactive Delirium, and Chloride
      Homeostasis.

PMID- 30113378
TI  - Efficacy and Safety of Procalcitonin Guidance in Patients With Suspected or
      Confirmed Sepsis: A Systematic Review and Meta-Analysis: Author Correction.

PMID- 30113380
TI  - Secretoneurin in Sepsis: Is It the Brain?

PMID- 30113381
TI  - The authors reply.

PMID- 30113379
TI  - Clinical Practice Guidelines for the Prevention and Management of Pain,
      Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients
      in the ICU.
AB  - OBJECTIVE: To update and expand the 2013 Clinical Practice Guidelines for the
      Management of Pain, Agitation, and Delirium in Adult Patients in the ICU. DESIGN:
      Thirty-two international experts, four methodologists, and four critical illness
      survivors met virtually at least monthly. All section groups gathered face-to
      face at annual Society of Critical Care Medicine congresses; virtual connections
      included those unable to attend. A formal conflict of interest policy was
      developed a priori and enforced throughout the process. Teleconferences and
      electronic discussions among subgroups and whole panel were part of the
      guidelines' development. A general content review was completed face-to-face by
      all panel members in January 2017. METHODS: Content experts, methodologists, and
      ICU survivors were represented in each of the five sections of the guidelines:
      Pain, Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and
      Sleep (disruption). Each section created Population, Intervention, Comparison,
      and Outcome, and nonactionable, descriptive questions based on perceived clinical
      relevance. The guideline group then voted their ranking, and patients prioritized
      their importance. For each Population, Intervention, Comparison, and Outcome
      question, sections searched the best available evidence, determined its quality,
      and formulated recommendations as "strong," "conditional," or "good" practice
      statements based on Grading of Recommendations Assessment, Development and
      Evaluation principles. In addition, evidence gaps and clinical caveats were
      explicitly identified. RESULTS: The Pain, Agitation/Sedation, Delirium,
      Immobility (mobilization/rehabilitation), and Sleep (disruption) panel issued 37
      recommendations (three strong and 34 conditional), two good practice statements,
      and 32 ungraded, nonactionable statements. Three questions from the patient
      centered prioritized question list remained without recommendation. CONCLUSIONS:
      We found substantial agreement among a large, interdisciplinary cohort of
      international experts regarding evidence supporting recommendations, and the
      remaining literature gaps in the assessment, prevention, and treatment of Pain,
      Agitation/sedation, Delirium, Immobility (mobilization/rehabilitation), and Sleep
      (disruption) in critically ill adults. Highlighting this evidence and the
      research needs will improve Pain, Agitation/sedation, Delirium, Immobility
      (mobilization/rehabilitation), and Sleep (disruption) management and provide the
      foundation for improved outcomes and science in this vulnerable population.

PMID- 30113382
TI  - Acidosis and Survival Among Septic Patients: A New Therapeutic Shield.

PMID- 30113383
TI  - The authors reply.

PMID- 30113384
TI  - Disparities in the Propensity for Interhospital Transfer Among Mechanically
      Ventilated Septic Patients.

PMID- 30113386
TI  - Culture-Negative Septic Shock Compared With Culture-Positive Septic Shock
      Mortality.

PMID- 30113385
TI  - The authors reply.

PMID- 30113387
TI  - The author replies.

PMID- 30113388
TI  - Septic Cardiomyopathy and Bacterial Exotoxins.

PMID- 30113389
TI  - The authors reply.

PMID- 30113390
TI  - Remote Photoplethysmographic Assessment of the Peripheral Circulation in Critical
      Care Patients Recovering from Cardiac Surgery.
AB  - PURPOSE: Camera-based photoplethysmography (cbPPG) remotely detects the volume
      pulse of cardiac ejection in the peripheral circulation. The cbPPG signal is
      sourced from the cutaneous microcirculation, yields a two-dimensional intensity
      map and is therefore an interesting monitoring technique. In this study we
      investigated, whether cbPPG is in general sufficiently sensitive to discern
      hemodynamic conditions. METHODS: cbPPG recordings of seventy patients recovering
      from cardiac surgery were analyzed. Photoplethysmograms were processed offline
      and the optical pulse power (OPP) of cardiac ejection was calculated. Hemodynamic
      data, image intensity and patient movements were recorded synchronously. The
      effects of hemodynamic parameters and measurement conditions on the patient's
      individual OPP variability and their actual OPP values were calculated in mixed
      effects regression models. RESULTS: Mean arterial pressure, pulse pressure, heart
      rate and central venous pressure significantly explained the individual OPP
      variability. Pulse pressure had the highest explanatory power (19.9%). Averaged
      OPP significantly increased with pulse pressure and mean arterial pressure (p <
      0.001, respectively) and decreased with higher heart rate (p = 0.024). Central
      venous pressure had a two-directional, non-significant effect on averaged OPP.
      Image intensity and patient movements did significantly affect OPP. After
      adjustment for hemodynamic co-variables and measurement conditions, the effect of
      pulse pressure and heart rate remained unchanged, whereas that of mean arterial
      pressure vanished. CONCLUSION: cbPPG is sensitive to hemodynamic parameters in
      critical care patients. It is a potential application for monitoring the
      peripheral circulation. Its value in a clinical setting has to be determined.

PMID- 30113391
TI  - Renal Resistive Index: Response to Shock and its Determinants in Critically Ill
      Patients.
AB  - INTRODUCTION: Shock is characterised by micro- and macrovascular flow impairment
      contributing to acute kidney injury (AKI). Routine monitoring of the circulation
      regards the macrocirculation but not the renal circulation which can be assessed
      with Doppler ultrasound as renal resistive index (RRI). RRI reflects resistance
      to flow. High RRI predicts persistent AKI. Study aims were to determine whether
      RRI is elevated in shock and to identify determinants of RRI. MATERIALS AND
      METHODS: This prospective observational cohort study included two cohorts of
      patients, with and without shock <24-h after intensive care admission. Apart from
      routine monitoring, three study measurements were performed simultaneously: RRI,
      sublingual microcirculation and bioelectral impedance analysis. RESULTS: 92
      patients were included (40 shock, 52 non-shock), median age was 69 [60-76] vs. 67
      [59-76], p = 0.541; APACHE III was 87 [65-119] vs. 57 [45-69], p < 0.001. Shock
      patients had higher RRI than patients without shock (0.751 [0.692-0.788] vs.
      0.654 [0.610-0.686], p < 0.001). Overall, high age, APACHE III score, lactate,
      vasopressor support, pulse pressure index (PPI), central venous pressure (CVP),
      fluid balance, and low pre-admission estimated glomerular filtration rate, mean
      arterial pressure (MAP), creatinine clearance and reactance/m were associated
      with high RRI at univariable regression (p < 0.01). Microcirculatory markers were
      not. At multivariable regression, vasopressor support, CVP, PPI and MAP,
      reactance/m and pre-admission eGFR were independent determinants of RRI (n = 92,
      Adj.R = 0.587). CONCLUSIONS: Patients with shock have a higher RRI than patients
      without. Independent determinants of high RRI were pressure indices of the
      systemic circulation, low membrane capacitance and pre-admission renal
      dysfunction. Markers of the sublingual microcirculation were not. TRIAL
      REGISTRATION CLINICALTRIALS.GOV:: NCT02558166. DATE OF REGISTRATION: 22-09-2015,
      retrospectively registeredThis is an open access article distributed under the
      terms of the Creative Commons Attribution-Non Commercial-No Derivatives License
      4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided
      it is properly cited. The work cannot be changed in any way or used commercially
      without permission from the journal. http://creativecommons.org/licenses/by-nc
      nd/4.0.

PMID- 30113392
TI  - Evidence Review Conducted for the Agency for Healthcare Research and Quality
      Safety Program for Improving Surgical Care and Recovery: Focus on Anesthesiology
      for Bariatric Surgery.
AB  - Enhanced recovery after surgery protocols for bariatric surgery are increasingly
      being implemented, and reports suggest that they may be associated with superior
      outcomes, reduced length of hospital stay, and cost savings. The Agency for
      Healthcare Research and Quality, in partnership with the American College of
      Surgeons and the Johns Hopkins Medicine Armstrong Institute for Patient Safety
      and Quality, has developed the Safety Program for Improving Surgical Care and
      Recovery. We have conducted an evidence review to select anesthetic interventions
      that positively influence outcomes and facilitate recovery after bariatric
      surgery. A literature search was performed for each intervention, and the highest
      levels of available evidence were considered. Anesthesiology-related
      interventions for pre- (carbohydrate loading/fasting, multimodal preanesthetic
      medications), intra- (standardized intraoperative pathway, regional anesthesia,
      opioid minimization and multimodal analgesia, protective ventilation strategy,
      fluid minimization), and postoperative (multimodal analgesia with opioid
      minimization) phases of care are included. We have summarized the best available
      evidence to recommend the anesthetic components of care for enhanced recovery
      after surgery for bariatric surgery. There is evidence in the literature, and
      from society guidelines, to support the Agency for Healthcare Research and
      Quality Safety Program for Improving Surgical Care and Recovery goals for
      bariatric surgery.

PMID- 30113393
TI  - Frailty Phenotypes and Relations With Surgical Outcomes: A Latent Class Analysis.
AB  - BACKGROUND: Frailty is an important concept in the care of older adults although
      controversy remains regarding its defining features and clinical utility. Both
      the Fried phenotype and the Rockwood deficit accumulation approaches cast frailty
      as a "burden" without exploring the relative salience of its cardinal markers and
      their relevance to the patient. New multifactorial perspectives require a
      reliable assessment of frailty that can validly predict postoperative health
      outcomes. METHODS: In a retrospective study of 2828 unselected surgical patients,
      we used item response theory to examine the ability of 32 heterogeneous markers
      capturing limitations in physical, functional, emotional, and social activity
      domains to indicate severity of frailty as a latent continuum. Eighteen markers
      efficiently indicated frailty severity and were then subject to latent class
      analysis to derive discrete phenotypes. Next, we validated the obtained frailty
      phenotypes against patient-reported 30-day postoperative outcomes using
      multivariable logistic regression. Models were adjusted for demographics,
      comorbidity, type and duration of surgery, and cigarette and alcohol consumption.
      RESULTS: The 18 markers provided psychometric evidence of a single reliable
      continuum of frailty severity. Latent class analyses produced 3 distinct
      subtypes, based on patients' endorsement probabilities of the frailty indicators:
      not frail (49.7%), moderately frail (33.5%), and severely frail (16.7%). Unlike
      the moderate class, severely frail endorsed emotional health problems in addition
      to physical burdens and functional limitations. Models adjusting for age, sex,
      type of anesthesia, and intraoperative factors indicated that severely frail
      (odds ratio, 1.89; 95% confidence interval, 1.42-2.50) and moderately frail
      patients (odds ratio, 1.31; 95% confidence interval, 1.03-1.67) both had higher
      odds of experiencing postoperative complications compared to not frail patients.
      In a 3-way comparison, a higher proportion of severely frail patients (10.7%)
      reported poorer quality of life after surgery compared to moderately frail (9.2%)
      and not frail (8.3%) patients (P < .001). There was no significant difference
      among these groups in proportions reporting hospital readmission (5.6%, 5.1%, and
      3.8%, respectively; P = .067). CONCLUSIONS: Self-report frailty items can
      accurately discern 3 distinct phenotypes differing in composition and their
      relations with surgical outcomes. Systematically assessing a wider set of domains
      including limitations in functional, emotional, and social activities can inform
      clinicians on what precipitates loss of physiological reserve and profoundly
      influences patients' lives. This information can help guide the current
      discussion on frailty and add meaningful clinical tools to the surgical practice.

PMID- 30113394
TI  - Midazolam Premedication Facilitates Mask Ventilation During Induction of General
      Anesthesia: A Randomized Clinical Trial.
AB  - BACKGROUND: During induction of general anesthesia, proper mask ventilation is
      crucial for supplying sufficient oxygen to unconscious patients. Midazolam has a
      relaxing effect on airway muscles. We hypothesized that sedative premedication
      with midazolam would facilitate mask ventilation during anesthetic induction.
      METHODS: Patients undergoing elective surgery under general anesthesia were
      randomized into 2 groups. The midazolam group received midazolam premedication at
      the reception area, 3 minutes before transfer to the operating room. Patients in
      the control group were treated with normal saline as a placebo. The primary
      outcome was difficulty of mask ventilation during induction, as evaluated using
      the Warters scales. RESULTS: A total of 97 patients completed the analysis: 49 in
      the control group and 48 in the midazolam group. The patients in the midazolam
      group showed a significantly lower mask ventilation difficulty score on the
      Warters scale than that of the control group (mean [standard deviation], 0.92
      [1.13] vs 0.19 [0.57]; estimated difference [95% confidence interval], 0.73 [0.37
      1.09]; P < .001). The incidence of difficult mask ventilation (>=2 Warters scale)
      was significantly lower in the midazolam group than in the control group (risk
      ratio [95% confidence interval], 0.15 [0.03-0.72]; P = .015). CONCLUSIONS: This
      randomized clinical trial demonstrated that midazolam premedication enhanced mask
      ventilation during induction of general anesthesia.

PMID- 30113395
TI  - Comparison of Intermittent Intravenous Boluses of Phenylephrine and
      Norepinephrine to Prevent and Treat Spinal-Induced Hypotension in Cesarean
      Deliveries: Randomized Controlled Trial.
AB  - BACKGROUND: Phenylephrine (PE) is currently the vasopressor of choice to prevent
      and treat spinal-induced hypotension at cesarean delivery (CD). However, its use
      is often associated with reflex bradycardia. Norepinephrine (NE) has been put
      forward as an alternative vasopressor during CD due to its ability to treat
      hypotension while maintaining heart rate (HR). Recent studies have focused on the
      role of NE used as an infusion with favorable results compared to PE. No studies
      have compared equipotent bolus doses of PE and NE at CD. We hypothesized that
      when used in equipotent doses as an intermittent bolus regimen to prevent and
      treat spinal-induced hypotension, NE would result in a reduction in the incidence
      of bradycardia compared to PE. METHODS: This was a double-blind, randomized
      clinical trial of women undergoing elective CD under spinal anesthesia. Women
      were randomized to receive either PE 100 ug or NE 6 ug when the systolic blood
      pressure (SBP) was below baseline. In addition to the randomized treatment,
      ephedrine was given intravenously to both groups if the SBP was below baseline
      and the HR <60 bpm or if the SBP was <80% of baseline for 2 consecutive readings.
      The primary outcome was bradycardia (HR <50 bpm) in the predelivery period.
      Secondary outcomes included hypotension (SBP <80% of baseline), hypertension (SBP
      >120% of baseline), tachycardia (HR >120% of baseline), >=2 episodes of
      bradycardia, nausea, vomiting, umbilical artery and vein blood gases, and Apgar
      scores. RESULTS: One hundred twelve patients were randomized. The incidence of
      bradycardia was lower in the NE group compared to the PE group (10.9% vs 37.5%; P
      < .001; difference [95% confidence interval {CI}], -26.8% [-41.8% to -11.7%]),
      implying an estimated 71% relative reduction (95% CI, 35%-88%). The distribution
      of the number of bradycardia episodes was also different between the 2 groups (P
      = .007). Further testing showed that the patients in the PE group had a higher
      risk of multiple bradycardia episodes (>=2 episodes) compared to the NE group
      (19.6% for PE versus 3.6% for NE; P = .008). The proportion of patients requiring
      rescue boluses of ephedrine was lower in the NE group compared to the PE group
      (7.2% for NE versus 21.4% for PE; P < .03; difference [95% CI], -14.3% [-27.0% to
      -1.6%]). No differences were observed between the 2 groups in the incidence of
      other secondary outcomes. CONCLUSIONS: When used as an intermittent bolus regimen
      to prevent and treat spinal-induced hypotension during CD, NE resulted in a
      significant reduction in the incidence of bradycardia as compared to an
      equipotent bolus regimen of PE. We conclude that the hemodynamic profile offered
      by NE during CD is superior to that of PE due to less fluctuations in HR and
      possibly cardiac output.

PMID- 30113396
TI  - Factors Associated With Recovery Room Intravenous Opiate Requirement After
      Pediatric Outpatient Operations.
AB  - BACKGROUND: Many children recovering from anesthesia experience pain that is
      severe enough to warrant intravenous (IV) opioid treatment within moments of
      admission to the postanesthesia care unit (PACU). Postoperative pain has several
      negative consequences; therefore, preventing significant PACU pain in children is
      both a major clinical goal and a moral/ethical imperative. This requires
      identifying patient-level and perioperative factors that may be used to predict
      PACU IV opioid requirement. This should allow for the development of personalized
      care protocols to prevent clinically significant PACU pain in children. Our
      objective was to develop prediction models enabling practitioners to identify
      children at risk for PACU IV opioid requirement after various painful ambulatory
      surgical procedures. METHODS: After Institutional Review Board approval,
      clinical, demographic, and anthropometric data were prospectively collected on
      1256 children 4-17 years of age scheduled for painful ambulatory surgery (defined
      as intraoperative administration of analgesia or local anesthetic infiltration).
      Three multivariable logistic regression models to determine possible predictors
      of PACU IV opioid requirement were constructed based on (1) preoperative history;
      (2) history + intraoperative variables; and (3) history + intraoperative
      variables + PACU variables. Candidate predictors were chosen from readily
      obtainable parameters routinely collected during the surgical visit. Predictive
      performance of each model was assessed by calculating the area under the
      respective receiver operating characteristic curves. RESULTS: Overall, 29.5% of
      patients required a PACU IV opioid, while total PACU analgesia requirement (oral
      or IV) was 41.1%. Independent predictors using history alone were female sex,
      decreasing age, surgical history, and non-Caucasian ethnicity (model area under
      the receiver operating characteristic curve [AUROC], 0.59 [95% confidence
      interval {CI}, 0.55-0.63]). Adding a few intraoperative variables improved the
      discriminant ability of the model (AUROC for the history + intraoperative
      variables model, 0.71 [95% CI, 0.67-0.74]). Addition of first-documented PACU
      pain score produced a substantially improved model (AUROC, 0.85 [95% CI, 0.82
      0.87]). CONCLUSIONS: Postoperative pain requiring PACU IV opioid in children may
      be determined using a small set of easily obtainable perioperative variables. Our
      models require validation in other settings to determine their clinical
      usefulness.

PMID- 30113397
TI  - The GCs-SGK1-ATP Signaling Pathway in Spinal Astrocytes Underlied Presurgical
      Anxiety-Induced Postsurgical Hyperalgesia.
AB  - BACKGROUND: Patients undergoing surgery often feel anxious. Accumulating evidence
      indicated that presurgical anxiety was related to the more severe postsurgical
      pain. An animal model was established that exposed Sprague-Dawley rats to a
      single-prolonged stress (SPS) procedure to induce presurgical anxiety-like
      behaviors. The experiment revealed that presurgical anxiety not only aggravated
      but also prolonged postsurgical pain. However, the underlying mechanisms were
      unknown. METHODS: The rats in group C + Cort, group I + Cort, group A + Cort, and
      group AI + Cort were injected with corticosterone. The rats in group C + RU486,
      group I + RU486, group A + RU486, and group AI + RU486 were injected with
      mifepristone (RU486). The rats in group C + GSK650394 and group AI + GSK650394
      were injected with GSK650394. The rats in group C + FC1 and group AI + FC1 were
      injected with fluorocitrate (FC) 30 minutes before SPS, 30 minutes before
      incision, and on postoperative days 1, 2, 3, 4, and 5. The rats in group C + FC2
      and group AI + FC2 were injected with FC on postoperative days 7, 8, 9, 10, 11,
      12, and 13. The paw withdrawal mechanical threshold was assessed 24 hours before
      SPS and from postoperative days 1 to 28. The level of corticosterone was
      determined by enzyme-linked immunosorbent assay. The expression of
      serum/glucocorticoid regulated kinase 1 (SGK1), interleukin-1beta, and tumor
      necrosis factor-alpha was visualized by Western blot. The concentrations of
      adenosine triphosphate (ATP) were measured by ATP assay kit. RESULTS: This study
      showed SPS elevated plasma glucocorticoids and ATP release from astrocytes, which
      meant the mechanical pain hypersensitivity in presurgical anxiety-induced
      postsurgical hyperalgesia was dependent on GCs-SGK1-ATP signaling pathway. SGK1
      protein level in astrocytes was increased in response to the glucocorticoid
      stimuli and enhanced the extracellular release of ATP. Furthermore, spinal
      astrocytes played a key role in the maintenance. Targeting spinal astrocytes in
      maintenance phase prevented the pathological progression. CONCLUSIONS: These data
      suggested an important signaling pathway that affected the pain sensitivity after
      operation caused by presurgical anxiety.

PMID- 30113398
TI  - Comparative Regimens of Lipid Rescue From Bupivacaine-Induced Asystole in a Rat
      Model.
AB  - BACKGROUND: It is currently unknown whether bupivacaine-induced asystole is
      better resuscitated with lipid emulsion (LE) administered peripherally or
      centrally, and whether different LE regimens administered peripherally
      demonstrated similar effects. In this study, we compared the effects of various
      regimens of lipid administration in a rat model of bupivacaine-induced asystole.
      METHODS: Forty-five adult male Sprague-Dawley rats were subjected to bupivacaine
      induced asystole and randomly divided into 3 lipid regimens groups: (1) 20% LE
      was administered continuously via the internal jugular vein (CV-infusion group);
      (2) 20% LE was administered continuously via the tail vein (PV-infusion group);
      and (3) 20% LE was administered as divided boluses via the tail vein (PV-bolus
      group). The maximum dose of LE did not exceed 10 mL.kg. External chest
      compressions were administered until the return of spontaneous circulation (ROSC)
      or the end of a 40-minute resuscitation period. RESULTS: The survival rate, rate
      of ROSC, systolic blood pressure, heart rate, heart rate-blood pressure product,
      and coronary perfusion pressure during 2-40 minutes in the CV-infusion and PV
      bolus groups were significantly higher than those in the PV-infusion group (P <
      .01), and the plasma total bupivacaine concentration and myocardial bupivacaine
      content were significantly lower (P < .05). Time to heartbeat return and time to
      ROSC in the CV-infusion and PV-bolus groups were significantly shorter than those
      in the PV-infusion group (P < .05). CONCLUSIONS: In the rat model of bupivacaine
      induced asystole, a divided LE bolus regimen administered peripherally provided a
      better resuscitation outcome than that of a continuous LE infusion regimen
      peripherally, and performed in a similar fashion as the continuous LE infusion
      regimen administered centrally.

PMID- 30113399
TI  - Postoperative Corneal Injuries: Incidence and Risk Factors.
AB  - BACKGROUND: Previous studies of postoperative corneal injury rates relied on
      provider-initiated incident reports, which may underestimate the true incidence.
      Postoperative administration of proparacaine eye drops is used almost exclusively
      to diagnose corneal injury; therefore, identifying instances of administration
      may provide a better estimate of corneal injuries. We compared proparacaine
      administration versus provider-initiated reports to determine rates of corneal
      injury. In addition, potential associations between clinical variables and injury
      were assessed with a matched case-control study. METHODS: The health records of
      132,511 sequential adult postanesthesia recovery room admissions (January 1, 2011
      to June 30, 2017) were reviewed to identify postoperative proparacaine
      administration and incident reports of corneal injury. Patients with corneal
      injury were matched with control patients at a 1:2 ratio to assess factors
      associated with injury. RESULTS: Proparacaine drops were administered to 442
      patients (425 patients received proparacaine for diagnosis and 17 patients
      received proparacaine for unrelated reasons). Incident reports identified 320
      injuries, and the aggregate corneal injury count was 436 (incidence, 3.3 injuries
      [95% confidence interval {CI}, 3.0-3.6] per 1000 cases of general anesthesia).
      Proparacaine administration had a greater case ascertainment percentage than
      incident reporting (97.5% vs 73.4%; P < .001). The matched case-control analysis
      found greater risks associated with longer duration of anesthesia (odds ratio,
      1.05 [95% CI, 1.03-1.07] per 10 minutes of anesthesia; P < .001) and nonsupine
      surgical position (odds ratio, 3.89 [95% CI, 2.17-6.98]; P < .001). Patients with
      injuries also had more evidence of sedation and agitation during anesthesia
      recovery. CONCLUSIONS: Calculation of incidence by using the administration of a
      medication (proparacaine eye drops) that is almost exclusively used to diagnose a
      specific injury (corneal injury) showed higher case ascertainment percentage than
      incident-reporting methods. Similar strategies could be used to monitor the rates
      of other adverse events.

PMID- 30113400
TI  - Informed Consent in Pediatric Anesthesia: A Narrative Review.
AB  - Informed consent for pediatric anesthesia challenges practitioners to navigate
      complex ethical, medical, and legal ambiguities. A patient's status as a minor
      does not negate the importance of his or her participation in the decision-making
      process but, rather, necessitates a nuanced evaluation of age and development to
      involve the patient to an appropriate extent. Given the complexities involved
      with pediatric informed consent in anesthesia practice and research, it is
      important to understand the experience of key stakeholders involved. For this
      review, we searched Medline, the Cochrane database, PROSPERO, and
      Clinicaltrials.gov for studies involving pediatric anesthesia informed consent.
      Inclusion and exclusion criteria were designed to select for studies that
      included issues related to informed consent as primary outcomes. The following
      data were extracted from included studies: title, authors, date of publication,
      study type, intervention, data collection method, participant type (ie, parent,
      pediatric patient, anesthesia provider), number of participants, pediatric
      patient age range, and primary outcome measures. Twenty-two articles were
      included for final review: studies of informed consent in pediatric anesthesia
      span many aspects of informed consent. Parental understanding has been studied
      most often (7/22 studies), followed by parental preferences (5/22 studies) and
      provider-related outcomes (5/22 studies) such as time spent interacting with
      patients, subjective reporting on amount of training related to informed consent,
      and provider satisfaction with the informed consent process. Outcomes pertaining
      to pediatric patients themselves constitute the smallest number of studies,
      including child anxiety (1/22), child understanding (1/22), and child refusal
      (1/22). Among the parties involved, parents have been most frequently identified
      as the subjects of these studies (2719/3805 subjects across all included studies,
      or 71% of all subjects). Pediatric patients are the least frequently involved
      subjects of studies that investigate informed consent in pediatric anesthesia
      (493/3805, or 13% of all subjects). Anesthesia providers and investigators have
      been study subjects (593/3805, or 16% of all subjects) for a range of topics
      including time spent interacting with patient, nature of informed consent
      conversation in relation to trainee status, satisfaction with informed consent
      process, and priorities for informed consent content. The aim of the present
      narrative review is to summarize the work that has been done on informed consent
      for pediatric anesthesia.

PMID- 30113401
TI  - Questions Raised by "Profound Intraoperative Hypotension Associated With
      Transfusion via the Belmont Fluid Management System".

PMID- 30113402
TI  - Feasibility of a Perioperative Text Messaging Smoking Cessation Program for
      Surgical Patients.
AB  - Although surgical patients who smoke could benefit from perioperative abstinence,
      few currently receive support. This pilot study determined the feasibility and
      acceptability of a perioperative text messaging smoking cessation program. One
      hundred patients (73% of eligible patients approached) enrolled in a surgery
      specific messaging service, receiving 1-3 daily messages about smoking and
      surgical recovery for 30 days. Only 17 patients unenrolled, the majority
      responded to prompting messages, and satisfaction with the program was high.
      Surgical patients are amenable to text message-based interventions; a future
      efficacy trial of text messaging smoking cessation support in surgical patients
      is warranted.

PMID- 30113404
TI  - Role of the Father of the Baby on Maternal Mental Health and Birth Outcomes Among
      Black Women in the United States.

PMID- 30113403
TI  - Vulnerabilities at First Sex and Their Association With Lifetime Gender-Based
      Violence and HIV Prevalence Among Adolescent Girls and Young Women Engaged in Sex
      Work, Transactional Sex, and Casual Sex in Kenya.
AB  - BACKGROUND: Adolescent girls and young women (AGYW) experience high rates of HIV
      early in their sexual life course. We estimated the prevalence of HIV-associated
      vulnerabilities at first sex, and their association with lifetime gender-based
      violence (GBV) and HIV. METHODS: We conducted a cross-sectional biobehavioral
      survey among AGYW (14-24 years) in Mombasa, Kenya in 2015. We compared the
      prevalence of first sex vulnerabilities across AGYW who self-identified as
      engaging in sex work (N = 408), transactional sex (N = 177), or casual sex (N =
      714) and used logistic regression to identify age-adjusted associations between
      first sex vulnerabilities and outcomes (GBV after first sex; HIV). RESULTS: The
      median age at first sex was 16 years (interquartile range 14-18). A total of
      43.6% received gifts or money at first sex; 41.2% and 11.2% experienced a coerced
      and forced first sex, respectively. First sex vulnerabilities were generally more
      common among AGYW in sex work. GBV (prevalence 23.8%) and HIV (prevalence 5.6%)
      were associated with first sex before age 15 [GBV adjusted odds ratio (AOR) 1.4,
      95% confidence interval (CI): 1.0 to 1.9; HIV AOR 1.9, 95% CI: 1.1 to 1.3];
      before or within 1 year of menarche (GBV AOR 1.3, 95% CI: 1.0 to 1.7; HIV AOR
      2.1, 95% CI: 1.3 to 3.6); and receipt of money (GBV AOR 1.9, 95% CI: 1.4 to 2.5;
      HIV AOR 2.0, 95% CI: 1.2 to 3.4). CONCLUSIONS: HIV-associated vulnerabilities
      begin at first sex and potentially mediate an AGYW's trajectory of risk. HIV
      prevention programs should include structural interventions that reach AGYW
      early, and screening for a history of first sex vulnerabilities could help
      identify AGYW at risk of ongoing GBV and HIV.

PMID- 30113406
TI  - Evaluation of Content on Commonly Used Web sites About Induction of Labor and
      Pain Management During Labor.
AB  - PURPOSE: The Internet is a common source of information for women during
      pregnancy. A multitude of data about birth can be found on the Internet, yet
      there are few guidelines to direct women to credible Web sites. Providers are
      often unaware of the health sites their patients access. The purpose of this
      study was to evaluate the quality of the written content on Web sites about
      induction of labor and pain management during labor. STUDY DESIGN AND METHODS:
      Descriptive study of 11 Web sites on induction of labor and pain management
      during labor. Searches on Google, Yahoo, and Bing were used to identify Web sites
      women use to seek information about labor and birth. The Web sites were evaluated
      using the Health Information Technology Institute (HITI) criteria, readability,
      and content criteria from UpToDate, an evidence-based, healthcare professional
      authored clinical resource. RESULTS: No Web sites met all the HITI criteria for
      both topics. One Web site was written at or below a seventh-grade reading level
      and six were written at or above a ninth-grade level. Although there was no
      perfect Web site, we noted government Web sites provided the highest quality
      information. CLINICAL IMPLICATIONS: Evaluation and discussion of Web sites used
      by pregnant women is needed. Nurses and other healthcare providers should be
      aware of what information exists and what Web sites women are using so they can
      guide women to credible, evidence-based data. Directing women to government
      sponsored Web sites on childbirth topics may help them access accurate
      information.

PMID- 30113405
TI  - Symptoms of Depression and Preterm Birth Among Black Women.
AB  - OBJECTIVE: To investigate the relationship between depressive symptoms and
      preterm birth (PTB) while adjusting for social support, both general and from the
      father of the baby. DESIGN: Retrospective study design. SETTING: Participants of
      the Life-course Influences of Fetal Environments (LIFE) study were recruited from
      a suburban hospital in Metropolitan Detroit, Michigan. PARTICIPANTS: The LIFE
      data consisted of 1,410 self-identified Black women age 18 to 45 years; 1,207
      women were included in this analysis. METHODS: Women were interviewed using a
      structured questionnaire administered 24 to 48 hours after birth during their
      postpartum hospitalization. Data on the newborns and their mothers' health were
      collected through medical record abstraction. The Center for Epidemiologic
      Studies Depression Scale (CES-D) was used to measure symptoms of depression. The
      CES-D scores >=23 were considered severe symptoms of depression. Modified Poisson
      regression models were built using a stepwise approach to assess association
      between symptoms of depression and PTB. RESULTS: Approximately, 17% of women had
      a PTB and 20% of women in the sample had a CES-D scores >=23. Women who had CES-D
      score >=23 were about 70% more likely to have a PTB compared with women with CES
      D scores <23 (PR = 1.68, 95% CI: 1.24-2.16) after adjustment for both general
      social support and father of the baby support. CONCLUSION: Women with CES-D
      scores >=23 were almost twice more likely to have PTB compared with women with
      CES-D scores <23. Referrals for mental healthcare providers might benefit women
      with symptoms of depression and improve birth outcomes. Nurses should encourage
      women to seek support beyond the father of the baby.

PMID- 30113407
TI  - The Smart Nutrition and Conditioning for Kids (SNACK) Program: An Approach to
      Increasing Nutrition Knowledge of Second-Grade Students.
AB  - BACKGROUND: The Smart Nutrition and Conditioning for Kids (SNACK) program was
      developed in response to the 2010 Childhood Obesity Study () recognizing a 49%
      childhood obesity rate in Trenton New Jersey. Lifestyle influences contributing
      to childhood obesity and Type 2 diabetes mellitus include poor food choices,
      inadequate access to healthy foods, decrease in physical activity, and
      insufficient access to safe play environments. METHODS: Second-grade students
      were selected by teachers to be in the SNACK intervention group or a control
      group based on their classroom assignment. The SNACK program integrated nutrition
      lessons to students in an urban and urban rim elementary school during regularly
      scheduled physical education class. Nutrition lesson plans were developed to
      educate the children on healthy eating in a fun, interactive manner. The SNACK
      intervention was performed twice a week for 8 weeks. Pre- and poststudy CATCH
      (CATCH [Coordinated Approach to Child Health] Global Foundation, 2017)
      Nutritional Knowledge surveys were completed by all of the participating
      children. RESULTS: Students who were offered the nutrition-based lessons (SNACK
      intervention group) performed better on their Healthy Choices survey (p < 0.05),
      but not the Nutritional Knowledge survey (p = 0.87), when compared with control
      group students. CONCLUSION: Results suggest that the SNACK program was a partial
      success and is one example of an interdisciplinary approach to early intervention
      that can teach young children how to choose healthy foods.

PMID- 30113408
TI  - Gender Identity: A Brief for Perinatal Nurses.

PMID- 30113409
TI  - Delayed School Starts for Middle and High Schools Makes Sense.

PMID- 30113410
TI  - Barriers to a Healthy Diet.

PMID- 30113411
TI  - The Millennium Villages Project: Outcomes Evaluation.

PMID- 30113413
TI  - Racial and Ethnic Disparities in Maternity Care in the United States Put Mothers
      and Babies at Risk.

PMID- 30113417
TI  - A Rare Case of Kikuchi-Fujimoto Disease With Diffuse Lung Involvement Presenting
      a Lymphatic-like Distribution on Thin-section Computed Tomography.

PMID- 30113418
TI  - A Sensible Approach to Diagnosing Cardiac Aneurysms, Pseudoaneurysms and Common
      Mimickers.
AB  - The heart can manifest a spectrum of focal convexities that range from
      insignificant crypts and diverticula to clinically relevant aneurysms and
      pseudoaneurysms. The distinction of a clinically significant lesion from a minor
      focal convexity can be challenging. This article outlines the various types of
      focal convexities on the basis of location within the heart and discusses unique
      morphologic and functional features to further characterize these entities. We
      also highlight the most critical clinical consequences of cardiac aneurysms and
      pseudoaneurysms such as thromboembolic events, aneurysm ruptures, intracardiac
      shunting, hemopericardium, and arrhythmias.

PMID- 30113416
TI  - Validation of the STA-Liatest DDi assay for exclusion of proximal deep vein
      thrombosis according to the latest Clinical and Laboratory Standards
      Institute/Food and Drug Administration guideline: results of a multicenter
      management study.
AB  - : Recommended strategy for venous thromboembolism (VTE) diagnosis includes the
      use of sensitive D-dimer (DDi) assays along with pretest probability (PTP)
      assessment. The Clinical and Laboratory Standards Institute (CLSI) recently
      issued a guideline (US FDA endorsed) on DDi in VTE exclusion. Such guideline
      specifies the ideal D-dimer assay characteristics and target population.
      Demonstrate STA-LiatestD-Di performance combined with a PTP score for proximal
      deep vein thrombosis (pDVT) exclusion in a CLSI compliant study. International,
      multicenter, prospective nonrandomized, noninterventional clinical outcome
      management study conducted in a standard-of-care setting. DDi was measured in DVT
      suspected consecutive low/moderate PTP outpatients, without conditions possibly
      impacting DDi values independently of thrombosis presence (age >80, pregnancy,
      postoperative, cancer) using a 0.5 MUg/ml (FEU) threshold for DVT exclusion.
      Results were used to determine test performance. One thousand two hundred and
      thirty-four patients (17 centers) signed informed consent. Nine hundred and
      eighty (mean age: 55) with valid results (494 negative DDi) completed the study
      (DVT prevalence: 8.7%). STA-LiatestD-Di performance exceeded CLSI/FDA
      requirements: sensitivity: 100% (95% CI 95.8-100%), NPV: 100% (95% CI 99.3-100%).
      STA-LiatestD-Di associated with PTP score showed excellent performance for pDVT
      exclusion, as recently demonstrated for pulmonary embolism. The assay allows safe
      VTE exclusion, avoiding unnecessary imaging tests.

PMID- 30113419
TI  - Comparison of Mechanical Stabilization of the Mandibular Angulus Fracture
      Fixation, With Titanium Plates and Screws, Resorbable Plates and Screws, and Bone
      Adhesives.
AB  - Mandibular fractures mostly occur at the angulus mandibula with a concurrent
      symphysis or corpus fracture on the opposite side. Misapplication can damage the
      nerves, adjacent teeth, soft tissues, and result in permanent tooth germs. In
      children, growth centers can be damaged, and this may result in asymmetry and
      retardation in growth and development. The aim of this study was to compare the
      mechanical stabilization after different techniques were used to create the
      mandibular angle fracture fixation and to create oblique fractures at mandible
      angles. This study included 32 hemi-mandibles that were divided into 4 groups
      with 8 units per group. All of the hemi-mandibles were fixated using different
      techniques; titanium mini plates and screws, resorbable mini plate and screws,
      and resorbable mini plates and cyanoacrylate bone adhesive only. The fixated
      mandibles were tested under molar masticatory forces, and their stabilization
      endurance was assessed. There were no significant differences in titanium mini
      plaque screw and resorbable plaque screw techniques under 40 N force. Resorbable
      and titanium plates and screws did not have any advantage over each other in
      terms of biomechanical behaviors. It is suitable to use adhesives in the
      reduction of complicated but nonload-bearing areas. The adhesive used in this
      study can adhere to the bone but should be further evolved for clinical use.

PMID- 30113420
TI  - A Simple and Reliable Submental Intubation Technique for Maxillofacial Fractures.
AB  - In 1986, Altemir first reported the use of submental intubation to avoid
      tracheotomy in patients with panfacial and midfacial fractures for whom
      intermaxillary fixation is necessary, but orotracheal and nasotracheal
      intubations are not recommended. This novel technique allowed intraoperative
      access to perform dental occlusion and reconstruction of the nasal pyramid in
      patients with skull base fractures. Herein, we describe a refined technique based
      on Altemir's original procedure. Seven male patients with panfacial fractures
      underwent submental intubation using our refined technique. The technique was
      developed after encountering a technical error with Altemir's original procedure.
      In this new technique, we employed a 2-0 silk suture guide to allow the passage
      of both the endotracheal and cuff-inflation tubes through the same tunnel created
      from the oral cavity to the submental area. The success rate of the refined
      technique was 100%, and there were no intraoperative or postoperative
      complications. There was 20 seconds of ventilation outage time in total.
      Endotracheal and cuff-inflation tubes were easily and quickly passed through the
      same submental tunnel. Our refined technique is simple, easy, safe, fast,
      inexpensive, and does not require specific materials. Submental scars were
      smaller and relatively inconspicuous in this study, compared to those reportedly
      associated with other modified techniques.

PMID- 30113421
TI  - Do Patients With More Education Receive More Subsidized Dental Care? Evidence
      From a Natural Experiment Using the Introduction of a School Reform in Norway as
      an Instrumental Variable.
AB  - BACKGROUND: In Norway, for several dental conditions, a substantial part of
      treatment costs are reimbursed by the National Insurance Scheme. Ideally, the
      probability of receiving subsidized dental care (SDC) should be independent of
      social determinants of health, such as education, so that dental services are
      accessible to everyone independent of their social status. OBJECTIVE: The main
      objective of this study was to estimate the causal effect of education on the
      probability of receiving SDC in the adult Norwegian population. RESEARCH DESIGN:
      During the period 1960-1972, all municipalities in Norway were required to
      increase the number of compulsory years of education from 7 to 9 years. This
      education reform was used to create exogenous variation in the education
      variable. Since municipalities implemented the reform at different times, we have
      both cross-sectional and time series variation in the reform instrument. Thus we
      were able to estimate the effect of education on the probability of receiving SDC
      by controlling for municipality fixed effects and trend variables. SUBJECTS: This
      study included all Norwegian adults, born during the period of 1947-1958.
      MEASURES: Information about education (number of years), whether the individuals
      had received SDC, place of residence (municipality) was collected. RESULTS: The
      probability of receiving SDC was found to increase by 2 percentage points per
      additional year of education. CONCLUSION: People with the most resources benefit
      the most from a universal welfare scheme that is addressed to reach everybody. We
      suggest providing information about the subsidy scheme in a way that is easily
      available and understandable to all individuals, independent of their level of
      education.

PMID- 30113422
TI  - Assessing Trends in Hospital System Structures From 2008 to 2015.
AB  - BACKGROUND: The Affordable Care Act introduced a major systematic change aimed to
      promote coordination across the care continuum. Yet, it remains unknown the
      extent to which hospital system structures have changed following the Affordable
      Care Act. The structure of hospital systems has important implications for the
      cost, quality, and accessibility of health services. OBJECTIVES: To assess trends
      in the structures of hospital systems. RESEARCH DESIGN: We aggregated data from
      the American Hospital Association (AHA) Annual Survey to the system level. Using
      a panel of hospital systems from 2008 to 2015, we assessed trends in the number
      of hospital systems, their size, ownership characteristics, geospatial
      arrangements, and integration with outpatient services. RESULTS: In the period
      2008-2015, there was an increasing percentage of hospitals that were system
      affiliated as well as growth in the number of hospital systems. A greater
      percentage of hospital systems that were organized as moderately centralized
      systems transitioned to centralized systems than to decentralized systems (19.8%
      vs. 4.7%; P<0.001). In terms of geospatial arrangement, a greater percentage of
      hub-and-spoke systems moved to a regional design than to national systems (20.0%
      vs. 8.2%; P<0.05). An increasing trend over time toward greater integration with
      outpatient services was found in a measure of total system level integration with
      outpatient services. CONCLUSIONS: Our findings suggest that hospital systems may
      be moving toward more regional designs. In addition, the trend of increasing
      integration offered across hospital systems overall, and as portion of total
      integration, suggests that systems may be increasing their services along the
      continuum of care.

PMID- 30113424
TI  - Improving Access to Primary Care.

PMID- 30113423
TI  - Geographic Variation in the Initiation of Commonly Used Opioids and Dosage
      Strength in United States Nursing Homes.
AB  - OBJECTIVES: To examine and quantify geographic variation in the initiation of
      commonly used opioids and prescribed dosage strength among older US nursing home
      residents. METHODS: We merged 2011 Minimum Data Set 3.0 to Medicare claims and
      facility characteristics data to conduct a cross-sectional study among long-stay
      nursing home residents who initiated short-acting opioids commonly used in
      nursing homes (oxycodone, hydrocodone, or tramadol). We examined geographic
      variation in specific opioids initiated and potentially inappropriate doses (>=50
      mg oral morphine equivalent/d) across hospital referral regions (HRRs).
      Multilevel logistic models quantified the proportional change in between-HRR
      variation and associations between commonly initiated opioids and inappropriate
      doses after adjusting for resident characteristics, facility characteristics, and
      state. RESULTS: Oxycodone (9.4%) was initiated less frequently than hydrocodone
      (56.2%) or tramadol (34.5%) but varied dramatically between HRRs (range, 0%
      74.5%). In total, resident/facility characteristics and state of residence,
      respectively explained 84.1%, 58.2%, 59.1%, and 46.6% of the between-HRR
      variation for initiating oxycodone, hydrocodone, tramadol, and inappropriate
      doses. In all cases, state explained the largest proportion of between-HRR
      variation. Relative to hydrocodone, residents initiating oxycodone were more
      likely (adjusted odds ratio, 5.00; 95% confidence interval, 4.57-5.47) and those
      initiating tramadol were less likely (adjusted odds ratio, 0.28; 95% confidence
      interval, 0.25-0.31) to be prescribed potentially inappropriately high doses.
      CONCLUSIONS: We documented extensive geographic variation in the opioid and dose
      initiated for nursing home residents, with state explaining the largest
      proportion of the observed variation. Further work is needed to understand
      potential drivers of opioid prescribing patterns at the state level.

PMID- 30113425
TI  - Interruptions to Intensive Care Nurses and Clinical Errors and Procedural
      Failures: A Controlled Study of Causal Connection.
AB  - OBJECTIVES: Interruptions occur frequently in the intensive care unit (ICU) and
      are associated with errors. To date, no causal connection has been established
      between interruptions and errors in healthcare. It is important to know whether
      interruptions directly cause errors before implementing interventions designed to
      reduce interruptions in ICUs. The aim of the study was to investigate whether ICU
      nurses who receive a higher number of workplace interruptions commit more
      clinical errors and procedural failures than those who receive a lower number of
      interruptions. METHODS: We conducted a prospective controlled trial in a high
      fidelity ICU simulator. A volunteer sample of ICU nurses from a single unit
      prepared and administered intravenous medications for a patient manikin. Nurses
      received either 3 (n = 35) or 12 (n = 35) scenario-relevant interruptions and
      were allocated to either condition in an alternating fashion. Primary outcomes
      were the number of clinical errors and procedural failures committed by each
      nurse. RESULTS: The rate ratio of clinical errors committed by nurses who
      received 12 interruptions compared with nurses who received 3 interruptions was
      2.0 (95% confidence interval = 1.41-2.83, P < 0.001). The rate ratio of
      procedural failures committed by nurses who received 12 interruptions compared
      with nurses who were interrupted three times was 1.2 (95% confidence interval =
      1.05-1.37, P = 0.006). CONCLUSIONS: More workplace interruptions during
      medication preparation and administration lead to more clinical errors and
      procedural failures. Reducing the frequency of interruptions may reduce the
      number of errors committed; however, this should be balanced against important
      information that interruptions communicate.

PMID- 30113426
TI  - Preexisting Diabetes Elevates Risk of Local and Systemic Complications in Acute
      Pancreatitis: Systematic Review and Meta-analysis.
AB  - The prevalence of diabetes mellitus (DM) and acute pancreatitis (AP) increases
      continuously, therefore, to understand the effects of preexisting diabetes on AP
      is crucially needed. Here, we performed a systematic review and meta-analysis in
      which AP patients including DM and non-DM groups were sorted. Several outcome
      parameters were analyzed, and the odds ratio (OR) and standardized mean
      difference with 95% confidence intervals (CIs) were calculated.We found 1417
      articles, of which 9 articles involving 354,880 patients were analyzed. More
      complications were seen in diabetic patients than in non-DM patients (OR, 1.553
      [95% CI, 1.266-1.904]; P < 0.001). Intensive care unit admission (OR, 1.799 [95%
      CI, 1.442-2.243]; P < 0.001) and renal failure (OR, 1.585 [95% CI, 1.278-1.966];
      P < 0.001) were more frequent in DM patients. There was a tendency of higher
      mortality and local complications (OR, 1.276 [95% CI, 0.991-1.643]; P = 0.059;
      and OR, 1.267 [95% CI, 0.964-1.659]; P = 0.090, respectively) in preexisting DM.
      Length of hospitalization was longer in DM patients (standardized mean
      difference, 0.217 [95% CI, 0.075-0.360]; P = 0.003). Preexisting DM negatively
      influences the outcome of AP and increases the risk of renal failure, local
      complications, and mortality.

PMID- 30113429
TI  - Acute Pancreatitis in Chronic Dialysis Patients.
AB  - The annual incidence of acute pancreatitis (AP) ranges from 4.9 to 73.4 cases per
      100,000 worldwide. Patients with end-stage renal disease on dialysis have an
      increased risk for developing AP compared with patients without renal disease. In
      addition to the general population risk factors, there are factors related to
      renal insufficiency and dialysis process that might predispose to AP in this
      population. Clinical features and diagnosis are the same as those in patients
      without renal failure; however, amylase and lipase levels should be interpreted
      cautiously as they might be falsely elevated in renal failure. In this article,
      we will describe the risk factors that are exclusive to this population. In
      addition, we will also focus on the laboratory indices and clinical features that
      are unique to this population with patients with end-stage renal disease.

PMID- 30113430
TI  - Adjuvant Treatment in Potentially Curable Pancreatic Cancer: Need to Include
      Tumor Location in the Equation?

PMID- 30113428
TI  - Pancreatic Cancer-Induced Cachexia and Relevant Mouse Models.
AB  - Pancreatic cancer is the third leading cause of cancer death in the United
      States, with projections that it will become the second leading cause by the year
      2030. It carries a dismal prognosis with a 5-year overall survival rate of less
      than 9% and is associated with numerous comorbidities, the most notable being
      cachexia. Defined as the loss of muscle mass not reversible by conventional
      nutritional support, cachexia is seen in over 85% of pancreatic cancer patients
      and contributes significantly to mortality, where nearly 30% of pancreatic cancer
      deaths are due to cachexia rather than tumor burden. Therefore, there is an
      urgent need to identify the mechanisms behind the development of muscle wasting
      in pancreatic cancer patients and design novel therapeutics targeting cachexia.
      This review highlights the current understanding surrounding the mechanisms
      underpinning the development of cachexia in pancreatic cancer, as well as the
      current mouse models of pancreatic cancer-induced muscle wasting described in the
      literature.

PMID- 30113431
TI  - Retrospective Analysis of Factors Associated With Venous Thromboembolism Among
      Pancreatic Cancer Patients: A Single Institution Experience.

PMID- 30113432
TI  - Anti-PD-1 Drug (Nivolumab) May Induce Acute and Life-Threatening Pancreatitis in
      Lung Cancer Patient: A Case Report.

PMID- 30113433
TI  - beta-Catenin Expression in Glucagon-Producing alpha Cells of Human Fetal
      Pancreatic Islets Suggests Wnt Signaling-Dependent Development.

PMID- 30113434
TI  - Cardiac Toxicity in a Patient Receiving Peptide Receptor Radionuclide Therapy.

PMID- 30113435
TI  - Hypothermia: A Sign of Sepsis in Young Infants in the Emergency Department?
AB  - OBJECTIVES: Diagnosis of sepsis in young infants can be challenging due to the
      nonspecific signs, which can include hypothermia. Whether the presence of
      hypothermia in young infants should prompt evaluation for serious infection is
      unclear. The objectives were to measure the prevalence of serious infection among
      infants <=60 days of age with hypothermia in the emergency department (ED) and
      determine other clinical features of hypothermic infants who have serious
      infection. METHODS: This is a retrospective analysis of all infants <=60 days
      seen in a children's hospital ED from April 2014 to February 2017. Primary
      outcome was presence of serious infection, defined as urinary tract infection,
      bacteremia, meningitis, pneumonia, or herpes virus infection. Hypothermia was
      defined as a rectal temperature of 36.0 degrees C or less. RESULTS: Of 4797
      infants <=60 days of age seen in the ED, 116 had hypothermia. The prevalence of
      serious infection was 2.6% (3/116) in hypothermic infants compared with 15.2%
      (61/401) in febrile infants (P < 0.01). Hypothermic infants with serious
      infections were more likely to have a history of prematurity, apnea, poor
      feeding, lethargy, ill-appearance, and respiratory signs than hypothermic infants
      without serious infection. All 3 hypothermic infants with serious infection had
      other concerning features. CONCLUSIONS: The prevalence of serious infection in
      hypothermic young infants in the ED is low. Serious infection is unlikely in
      infants with isolated hypothermia.

PMID- 30113436
TI  - Pulmonary Alveolar Proteinosis in Hereditary and Autoimmune Forms With 2 Cases.
AB  - Pulmonary alveolar proteinosis (PAP) is a respiratory pathology characterized by
      the accumulation and increase of surfactant-derived material in the lungs. In
      clinical practice, PAP may present as the primary form, which includes autoimmune
      and hereditary PAP, or as the secondary form. Diffuse alveolar radiopacities on
      chest x-ray and the crazy-paving pattern on high-resolution computed tomography
      are important, although not specific findings for PAP. Bronchoalveolar lavage
      biopsy is a diagnostic method, and whole-lung lavage remains the criterion
      standard for the treatment of PAP. Evidence is required regarding treatment with
      exogenous anti-granulocyte/macrophage colony-stimulating factor.Here, we present
      a 13-year-old male patient with hereditary PAP and a 15-year-old female patient
      with autoimmune PAP who presented with complaints of easy fatigability and
      weakness to emphasize the importance of keeping in mind PAP as a differential
      diagnosis in patients with respiratory failure findings.

PMID- 30113437
TI  - Nationwide Survey of Hospitalization Due to Pediatric Food-Induced Anaphylaxis in
      the United States.
AB  - OBJECTIVE: Anaphylaxis is a common, serious, systemic allergic reaction. In the
      United States, the change of annual hospitalization rates by anaphylaxis-trigger
      foods and risk factors associated with severity remain unclear. METHODS: Hospital
      discharge records of food-induced anaphylactic reactions of individuals younger
      than 20 years were obtained from Kids' Inpatient Database in 2006, 2009, and 2012
      and were weighted to estimate the number of hospitalizations in the United
      States. We identified annual hospitalization rates by patients' characteristics
      and anaphylaxis-trigger foods and investigated factors associated with severity
      and use of mechanical ventilation with multivariable logistic regression.
      RESULTS: A total of 3427 hospitalizations were obtained, and annual
      hospitalization rates showed a significantly increasing trend from 1.2 per
      100,000 children in 2006 to 1.5 per 100,000 children in 2012 (P < 0.001). The
      leading causes of hospitalizations due to food-induced anaphylaxis were peanuts
      (0.35-0.48 per 100,000 children), tree nuts and seeds (0.20-0.32 per 100,000
      children), and milk products (0.09-0.13 per 100,000 children), with significantly
      increasing trends during 2006-2012. Milk products were significantly associated
      with severity (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.3-2.9). Ages
      between 13 and 20 years (OR, 2.7; 95% CI, 1.4-5.1) and comorbidity of asthma (OR,
      2.1; 95% CI, 1.3-3.4) were significantly associated with the use of mechanical
      ventilation. CONCLUSIONS: The annual hospitalization rates in the entire United
      States showed an increasing trend during 2006-2012. The rates of peanuts, tree
      nuts and seeds, and milk products demonstrated upward trends. Milk products, ages
      between 13 and 20 years, and comorbidities of asthma were related to severity and
      morbidity.

PMID- 30113427
TI  - Germline Variants and Risk for Pancreatic Cancer: A Systematic Review and
      Emerging Concepts.
AB  - Pancreatic cancer requires many genetic mutations. Combinations of underlying
      germline variants and environmental factors may increase the risk of cancer and
      accelerate the oncogenic process. We systematically reviewed, annotated, and
      classified previously reported pancreatic cancer-associated germline variants in
      established risk genes. Variants were scored using multiple criteria and binned
      by evidence for pathogenicity, then annotated with published functional studies
      and associated biological systems/pathways. Twenty-two previously identified
      pancreatic cancer risk genes and 337 germline variants were identified from 97
      informative studies that met our inclusion criteria. Fifteen of these genes
      contained 66 variants predicted to be pathogenic (APC, ATM, BRCA1, BRCA2, CDKN2A,
      CFTR, CHEK2, MLH1, MSH2, NBN, PALB2, PALLD, PRSS1, SPINK1, TP53). Pancreatic
      cancer risk genes were organized into key biological mechanisms that promote
      pancreatic oncogenesis within an oncogenic model. Development of precision
      medicine approaches requires updated variant information within the framework of
      an oncogenic progression model. Complex risk modeling may improve interpretation
      of early biomarkers and guide pathway-specific treatment for pancreatic cancer in
      the future. Precision medicine is within reach.

PMID- 30113438
TI  - Acute Hemorrhagic Edema of Infancy With Associated Hemorrhagic Lacrimation.
AB  - Acute hemorrhagic edema of infancy is a rare leukocytoclastic vasculitis that
      affects infants and children aged 4 to 24 months. We report a case of a 5-month
      old girl with purpuric lesions with associated hemorrhagic lacrimation and
      epistaxis.

PMID- 30113439
TI  - Domestically Acquired Aural Myiasis in a Tennessee Girl.
AB  - We present the rare case of a 12-year-old girl from Tennessee with domestically
      acquired aural myiasis.

PMID- 30113440
TI  - Vascular Endothelial Growth Factor Enhances Proliferation of Human Tenocytes and
      Promotes Tenogenic Gene Expression.
AB  - BACKGROUND: In obtaining human tenocytes for tendon tissue engineering, a low
      proliferation rate and phenotype loss during passaging is a problem. It was the
      authors' aim to evaluate the influence of vascular endothelial growth factor
      (VEGF) on human tenocyte growth and gene expression. METHODS: Human tenocytes
      were exposed to human VEGF in various concentrations (5, 10, and 20 ng/ml) for 5
      days. Cell proliferation was counted and expression of tendon-related genes was
      analyzed. RESULTS: Tenocyte count was 1.4 * 10/ml, 2.7 * 10/ml, 2.3 * 10/ml, and
      3.7 * 10/ml for 0, 5, 10, and 20 ng/ml VEGF, respectively. Expression of Col1 was
      up-regulated 6.4 +/- 4.2-fold, 60.1 +/- 21.6-fold, and 15.8 +/- 10.2-fold for 5,
      10, and 20 ng/ml VEGF; all differences were significant with p < 0.05. Col3 was
      down-regulated to 0.2 +/- 0.1-fold, 0.3 +/- 0.1-fold, and 0.1 +/- 0.03-fold for
      5, 10, and 20 ng/ml VEGF; all differences were significant. Eln was up-regulated
      2.3 +/- 1.7-fold, 25.5 +/- 10.9-fold, and 16.6 +/- 9.0-fold for 5, 10, and 20
      ng/ml VEGF; differences were significant for 10 and 20 ng/ml VEGF. TSC was down
      regulated to 0.3 +/- 0.1-fold and 0.3 +/- 0.1-fold for 5 and 20 ng/ml VEGF;
      differences were significant for 5 and 20 ng/ml. SCX was up-regulated to 31.3 +/-
      8.5-fold, 49.1 +/- 23.4-fold, and 20.9 +/- 9.5-fold for 5, 10, and 20 ng/ml VEGF;
      all changes were significant. CONCLUSIONS: VEGF enhances proliferation and
      expression of tendon-related genes in human tenocytes. It could therefore be a
      useful addition for tenocyte cultivation.

PMID- 30113441
TI  - A Review of Validated Quality-of-Life Patient-Reported Outcome Measures in
      Pediatric Plastic Surgery.
AB  - BACKGROUND: There has been an exponential increase in the number of patient
      reported outcome measures in plastic surgery. The authors reviewed the
      reliability, validity, and practicality of the most frequently used patient
      reported outcome measures in pediatric plastic surgery research. METHODS: A
      review of the literature from January of 2010 to June of 2015 was conducted to
      identify patient-reported outcome measures in pediatric plastic surgery. Patient
      reported measures used in five articles with two validation studies were included
      for analysis and classified as generic, disease-specific, and mental health. The
      type of validation used and reliability scores were compared across each class of
      outcome measure. The practicality of each measure was determined by the frequency
      of use and the number of items and cost. RESULTS: Of the 173 unique patient
      reported outcome measures identified, 14 were included for analysis and
      classified as generic (n = 7), disease-specific (n = 4), and mental health (n =
      3). The majority of all measures used construct validity. Disease-specific
      measures had the highest distribution of domains related to physical functioning,
      the same domain also found to have the highest reliability scores. A patient
      reported outcome measure's frequency of use was not associated with its number of
      items or cost. CONCLUSIONS: This review found that generic patient-reported
      outcome measures were used most often, construct validity was used most
      frequently, physical functioning domains had the highest reliability, and the
      number of items or cost of a patient-reported outcome measure was not related to
      its frequency of use. Considered together, this information may inform the future
      development or selection of patient-reported outcome measures in pediatric
      plastic surgery.

PMID- 30113442
TI  - Combined Carpal Tunnel Release and Palmar Fasciectomy for Dupuytren's Contracture
      Does Not Increase the Risk for Complex Regional Pain Syndrome.
AB  - BACKGROUND: Hand surgery dogma suggests that simultaneous surgical treatment of
      carpal tunnel syndrome and Dupuytren's contracture results in an increased
      incidence of complex regional pain syndrome. As a result, many surgeons do not
      perform surgery for the two conditions concurrently. The authors' goal was to
      determine the extent of this association. METHODS: The authors identified all
      patients undergoing surgical treatment for carpal tunnel syndrome, Dupuytren's
      contracture, or both between April of 1982 and March of 2017 using the Indiana
      Network for Patient Care, a large, multi-institutional, statewide information
      exchange. Demographics, comorbidities, and 1-year postoperative incidence of
      complex regional pain syndrome were recorded. RESULTS: A total of 51,739 patients
      (95.6 percent) underwent carpal tunnel release only, 2103 (3.9 percent) underwent
      palmar fasciectomy only, and 305 (0.6 percent) underwent concurrent carpal tunnel
      release and palmar fasciectomy. There was no difference in the likelihood of
      developing complex regional pain syndrome (p = 0.163) between groups. Independent
      risk factors for developing complex regional pain syndrome were younger age;
      anxiety; depression; epilepsy; gout; and history of fracture of the radius, ulna,
      or carpus. CONCLUSIONS: Concurrent carpal tunnel release and palmar fasciectomy
      is not associated with an increased risk for developing complex regional pain
      syndrome. Patient demographics, medical comorbidities, and a history of upper
      extremity trauma are associated with the development of complex regional pain
      syndrome after surgery and should be discussed preoperatively as potential risk
      factors. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30113443
TI  - Intracranial Volume and Head Circumference in Children with Unoperated Syndromic
      Craniosynostosis.
AB  - BACKGROUND: When analyzing intracranial volume gain resulting from operative
      intervention in craniosynostosis, it is necessary to understand the underlying
      growth. The authors sought to create comprehensive intracranial volume and
      occipitofrontal circumference growth charts, as measured on unoperated
      craniosynostotic children, and aimed to investigate whether intracranial volume
      and occipitofrontal circumference could act as proxy measures for each other.
      METHODS: All preoperative Great Ormond Street Hospital patients with a diagnosis
      of Apert, Crouzon-Pfeiffer, or Saethre-Chotzen syndrome from the year 2004 onward
      were considered for this study. A control group of unaffected Great Ormond Street
      Hospital patients were also measured. Intracranial volume and occipitofrontal
      circumference were measured on the same scans. To study correlation between
      intracranial volume and occipitofrontal circumference, logarithmic fits were
      assessed. RESULTS: One hundred forty-seven craniosynostotic children with 221
      preoperative scans were included (81 Apert, 81 Crouzon, 31 Pfeiffer, and 28
      Saethre-Chotzen). The control group comprised 56 patients with 58 scans. Apert
      intracranial volume curves were significantly larger than those of other
      syndromes from 206 days onward; occipitofrontal circumference curves were not
      significantly different. The correlation coefficient between intracranial volume
      and occipitofrontal circumference was R = 0.87 for all syndromes combined and R =
      0.91 for the control group. CONCLUSIONS: Apert syndrome children have a larger
      intracranial volume than children with other syndromic craniosynostotic
      conditions and unaffected children but maintain a similar occipitofrontal
      circumference. This study demonstrates high correlation between intracranial
      volume and occipitofrontal circumference with clinical care implications. The
      authors' reference growth curves can be used to monitor intracranial volume
      change over time and correct operative change for underlying growth.

PMID- 30113444
TI  - Mechanical Loading Improves Engineered Tendon Formation with Muscle-Derived
      Cells: An In Vivo Analysis.
AB  - BACKGROUND: The authors' previous study showed that muscle-derived cells could
      regenerate strong engineered tendon with better tissue structure. However, little
      was known about the mechanism of neotendon built by muscle-derived cells, and the
      development and maturation of the cells. The authors hypothesized that mechanical
      loading modulated this process. The aim of this study was to investigate whether
      mechanical loading could regulate muscle-derived cell-based engineered tendon
      formation and maturation. METHODS: Muscle-derived cells were isolated, expanded,
      and seeded onto polyglycolic acid fibers that formed a cell-scaffold complex.
      After in vitro culture for 2 weeks, half of them were implanted without loading
      and the other half were sutured to mouse fascia that could provide a natural
      dynamic loading. At 12 and 24 weeks after implantation, histologic examinations,
      ultrastructure, and biomechanical characteristics were evaluated. RESULTS: Gross
      observation results showed that under mechanical loading, neotendon tissue could
      be generated with muscle-derived cells and the tissue structure became more
      mature with the increase of culture time. Well-organized aligned collagen fibers
      and elongated morphologic cells were observed on histologic examination under
      mechanical loading. In contrast, the nonload group failed to form neotendon, but
      formed disorganized fibrous tissue with significantly worse mechanical properties
      and poor collagen fibril structure. CONCLUSIONS: This study demonstrates that
      mechanical loading is indispensable in tendon tissue engineering with muscle
      derived cells. Although muscle-derived cells have a potential advantage in
      neotendon regeneration, stress deprivation resulted in a distinctly inferior
      maturity level of engineered tendon.

PMID- 30113445
TI  - Validity of the Tinel Sign and Prevalence of Tibial Nerve Entrapment at the
      Tarsal Tunnel in Both Diabetic and Nondiabetic Subjects: A Cross-Sectional Study.
AB  - BACKGROUND: Nerve entrapments like carpal tunnel syndrome are more prevalent in
      patients with diabetes, especially in those with diabetic polyneuropathy. Our
      study aims were to investigate the validity of the Tinel sign in diagnosing
      tibial neuropathy and determine the prevalence of tibial nerve entrapment in both
      a diabetic and nondiabetic population. METHODS: Two hundred forty nonneuropathic
      subjects with diabetes and 176 diabetic subjects with neuropathy participating in
      the prospective Rotterdam Diabetic Foot Study and 196 reference subjects without
      diabetes and without neuropathy complaints were evaluated. All subjects underwent
      sensory testing of the feet, and complaints were assessed using the Michigan
      Neuropathy Screening Instrument. The Tinel sign was defined as discriminative and
      valid for diagnosing tibial nerve entrapment when the nerve-related Michigan
      Neuropathy Screening Instrument subscore of neuropathic symptoms differed at
      least 5 percent between the Tinel-positive and Tinel-negative subjects. When the
      sign was valid, prevalence estimates of tibial nerve entrapment at the tarsal
      tunnel were calculated. RESULTS: Significantly more neuropathic symptoms (p <
      0.002) and higher sensory thresholds (p < 0.0005) were observed in (compressed)
      tibial nerve-innervated areas, indicating that a positive Tinel sign at the
      tarsal tunnel is a valid measure of tibial nerve abnormality. The prevalence of
      tibial nerve entrapment in diabetic patients was 44.9 percent (95 percent CI,
      40.1 to 49.7 percent) versus 26.5 percent (95 percent CI, 20.3 to 32.7 percent)
      in healthy controls (p < 0.0001). CONCLUSIONS: Tibial nerve entrapment is more
      prevalent in diabetic subjects than in controls. The significantly more
      frequently reported neuropathic complaints and concomitant sensory disturbances
      provide evidence for the role of superimposed entrapment neuropathy in diabetes
      related neuropathy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

PMID- 30113446
TI  - Cephalic Rotation of the Nasal Tip.
AB  - The position of the nasal tip holds important aesthetic significance. Cephalic
      rotation of the nasal tip is a frequent motivating factor for patients seeking
      rhinoplasty. The position of the nasal tip is a complex interplay of the size,
      morphology, and position of several anatomic components of the lower one-third of
      the nose. Cephalic rotation can be achieved by way of six different methods. The
      indirect methods promote passive cephalic rotation and include cephalic trim of
      the lower lateral cartilages, caudal trim of the upper lateral cartilages, and
      caudal septal trim. Direct methods involve precise repositioning of the domes and
      include shortening the lateral crura, lateral domal relocation, and the tip
      rotation suture. Used alone or in combination, these techniques and their subtle
      variations, represent comprehensive and effective methods to achieve cephalic
      rotation of the nasal tip.

PMID- 30113447
TI  - Simultaneous Reconstruction of the Lower Lip with Gracilis Functioning Free
      Muscle Transplantation for Facial Reanimation: Comparison of Different
      Techniques.
AB  - BACKGROUND: Functioning free muscle transplantation is currently the gold
      standard for the reconstruction of facial paralysis, focusing more on the upper
      lip reconstruction rather than on the lower lip. This study aimed to compare
      different lower lip reconstructive methods when performing functioning free
      muscle transplantation for facial reanimation. METHODS: A retrospective review of
      functioning free muscle transplantation for facial reanimation from 2007 to 2015
      was performed. Patients were divided into three groups: in group 1 (n = 15), a
      free plantaris tendon graft anchored to the gracilis muscle was passed into the
      lower lip to create a loop within; in group 2 (n = 12), an aponeurosis tail of
      the gracilis muscle was attached to the lower lip; and in group 3 (n = 18), no
      suspension of the lower lip was performed. All patients had at least 2 years of
      follow-up. Outcomes were assessed by photographs and videos, including subjective
      evaluation of midline deviation and horizontal tilt and objective analysis of
      smile dimensions and area. RESULTS: A total of 45 patients were included. Results
      from the subjective evaluation demonstrate group 1 patients having the best
      improvement (overall score: p = 0.004 and p = 0.005, Fisher's exact test). The
      objective evaluation showed group 1 and 2 patients with better results compared
      with group 3 (horizontal component, p = 0.009; vertical component, p = 0.004;
      area distribution, p < 0.001, Kruskal-Wallis test). CONCLUSIONS: Both plantaris
      tendon graft and gracilis aponeurosis achieved better improvement in subjective
      and objective evaluations than those who had no reconstruction of the lower lip.
      In particular, the plantaris tendon graft can achieve the most lower lip
      excursion with overall improved symmetry. CLINICAL QUESTION/LEVEL OF EVIDENCE:
      Therapeutic, III.

PMID- 30113448
TI  - Discussion: Simultaneous Reconstruction of the Lower Lip with Gracilis
      Functioning Free Muscle Transplantation for Facial Reanimation: Comparison of
      Different Techniques.

PMID- 30113449
TI  - Outcome and Complications following Vertical Rectus Abdominis Myocutaneous Flap
      Surgery to Reconstruct Sacrectomy Defects.
AB  - BACKGROUND: The vertical rectus abdominis myocutaneous flap has been used to
      reliably reconstruct posterior soft-tissue defects following resection of high
      sacral tumors, providing skin and soft-tissue bulk. Current literature examining
      the use of these flaps for high sacral reconstruction is limited. The purpose of
      this study was to report the authors' institution's outcome on the use of the
      vertical rectus abdominis myocutaneous flap to reconstruct a high sacral defect
      following an oncologic resection. METHODS: Eighty-seven patients (29 female and
      58 male) underwent vertical rectus abdominis myocutaneous flap surgery to
      reconstruct a posterior wound following high sacral tumor resection from 1994 to
      2016. The mean age and body mass index were 52 years and 27.8 kg/m, respectively.
      The mean follow-up was 6 years. RESULTS: Sixty-eight patients (79 percent)
      sustained a complication, most commonly a wound complication [n = 41 (47
      percent)]. Twenty patients (23 percent) sustained a donor-site wound
      complication, most commonly a wound dehiscence (n = 10). Complications resulted
      in a reoperation in 44 patients (51 percent), with total flap failure occurring
      in one (1 percent). Preoperative radiotherapy and obesity were found to increase
      the risk of wound complications (p = 0.004 and p = 0.02, respectively) and deep
      infection (p = 0.03 and p = 0.02, respectively). CONCLUSIONS: Complications were
      common following vertical rectus abdominis myocutaneous flap surgery; however,
      total flap loss was not. Patients with obesity and preoperative radiotherapy
      should be cautioned on their increased risk of complications. Currently, the
      vertical rectus abdominis myocutaneous flap is the authors' preferred means of
      soft-tissue reconstruction following high sacral tumor resection. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

PMID- 30113450
TI  - Complete androgen insensitivity syndrome in a young woman with metabolic disorder
      and diabetes: A case report.
AB  - RATIONALE: Androgen insensitivity syndrome (CAIS) is a rare X-linked recessive
      androgen receptor disorder characterized by complete resistance to the actions of
      androgen in an individual with 46,XY karyotype. Metabolic disorder and diabetes
      has been rarely reported in these patients. PATIENT CONCERNS: A 22-year-old
      female patient was admitted to our center for the evaluation of high blood sugar.
      The central obesity, lipid dysfunction, and diabetes were found in the patient.
      The patient also presented as primary amenorrhea and poor secondary sex
      characteristics after puberty. DIAGNOSES: The diagnosis of CAIS in this patient
      was established by infantile female genitalia, absence of ovary and uterus,
      history of gonadectomy, 46,XY karyotype, and carried a mutation c.2751C>G (p.917F
      > L) in androgen receptor gene. INTERVENTION: The patient was treated by insulin,
      metformin, statins and estrogen. OUTCOMES: After 6 months follow-up, blood sugar
      and lipid profiles were normal, but breast development and weight loss were not
      obvious. LESSONS: We report a case of CAIS in a 22-year-old female accompanying
      central obesity, dyslipidemia, and diabetes mellitus. It is extremely important
      to recognize special type diabetes among the young-onset diabetic patients, and
      this case will provide further evidence of a link between impaired androgen
      receptor signaling and metabolic regulation.

PMID- 30113451
TI  - The utility of FDG-PET/CT imaging in the evaluation of multicentric
      reticulohistiocytosis: A case report.
AB  - INTRODUCTION: Multicentric reticulohistiocytosis (MRH) is a rare histiocytic
      disorder that involves the skin, joints, and visceral organs. CASE PRESENTATION:
      We report a 67-year-old woman with MRH who presented with a 2-years history of
      polyarthralgia and skin nodules. Her symptoms were an inflammatory
      polyarthropathy with punched-out lesions of the distal interphalangeal (DIP)
      joints of both hands. Doppler ultrasonography of the hands showed large bone
      erosions with power Doppler signals in the DIP joints. F-fluorodeoxyglucose
      positron emission tomography/computed tomography (FDG-PET/CT) demonstrated
      increased FDG uptake in cutaneous papules surrounding the affected joints,
      suggesting an inflammatory process. There was no evidence of malignancy. Biopsy
      samples of skin nodules exhibited dermal infiltration with CD68-positive
      histiocytes and multinucleated giant cells. The patient was diagnosed with MRH
      and treated with combination therapy comprising a steroid (prednisolone),
      tacrolimus, methotrexate, and infliximab, which resulted in clinical improvement.
      Following infliximab treatment, there was a significant decrease in a bone
      resorption marker (tartrate-resistant acid phosphatase 5b: TRACP-5b), suggesting
      that tumor necrosis factor-alpha targeting therapy may inhibit osteoclast
      formation and resorption activity in patients with MRH. CONCLUSION: MRH is a
      progressive destructive arthritic condition, and early diagnostic and therapeutic
      strategies are necessary to improve the outcome. FDG-PET/CT and joint
      ultrasonography might be noninvasive imaging modalities that could help diagnose
      MRH.

PMID- 30113452
TI  - Nurses' knowledge and practices in the face of the challenge of using the
      systematization of nursing care as an instrument of assistance in a first aid in
      Brazil.
AB  - OBJECTIVE: To analyze the performance of nurses in the implementation of nursing
      care systematization (NCS). This study is a descriptive research developed from a
      qualitative approach. The content analysis (CA) must be developed through 3
      chronological poles allowing the researcher to construct an analysis structure
      that corresponds to the needs of the research and the objectives of the proposed
      research; The chronological poles of CA are described as: Phase 1-preanalysis,
      phase 2-exploration of the material: phase 3-treatment of the results obtained
      and interpretation. Only a semistructured interview will be conducted with the
      research subjects who meet the inclusion criteria of the study, preserving the
      identity of the individuals and guaranteeing the right to quit the research at
      any time during the interview. The Research Ethics Committee of Hospital of the
      clinics of Acre, Brazil (Amazon region) under the opinion no. 1.460.960 approved
      this protocol. The clinical protocol was registered in the "Brazilian Registry of
      Clinical Trials" validated by the World Health Organization, and received
      clinical trials "RBR-882rg2."

PMID- 30113453
TI  - Dermatomyositis as an extrahepatic manifestation of hepatitis B virus-related
      hepatocellular carcinoma: A case report and literature review.
AB  - RATIONALE: Dermatomyositis is an idiopathic inflammatory myopathy with specific
      cutaneous manifestations, which is closely associated with malignancy. However,
      the exact mechanism remains elusive. Even less is known about dermatomyositis
      with hepatocellular carcinoma (HCC). PATIENT CONCERNS: We reported a case of
      dermatomyositis with hepatitis B virus (HBV) infection. He incidentally found his
      lower limbs little weakness accompanied with his wrist erythema. He was found
      HBsAg positive for forty years with slightly positive of alpha-fetal protein
      (AFP). DIAGNOSES: A dermapathology from his hand-wrist lesions demonstrated a
      scattered inflammatory infiltrate around the capillaries of the dermis. Abdominal
      enhanced computer tomography (CT) revealed infiltrative HCC affecting the whole
      liver, accompanied by liver metastasis and liver cirrhosis. Liver tumor needle
      biopsy pathology showed HCC with moderate differentiation. The left
      supraclavicular lymph node needle biopsy pathology confirmed metastasic HCC.
      INTERVENTIONS: Prednisolone was gradually withdrawn with the introduction of
      Entecavir 0.5 mg daily. Radiofrequency ablation therapy for liver tumor was
      performed once in order to decrease the tumor load. OUTCOMES: His muscle power
      improved to grade 4+/5 in the lower limb one month after anti-HBV treatment.
      However, this patient died finally from liver failure due to the development of
      liver tumor. LESSONS: In the coming clinic work, we must pay more attention to
      the extrahepatic disorder induced by HBV. On treating experience, glucocorticoid
      administration is often contraindicated for HBV infected patients because of its
      potential promotion of HBV replication. Thus, it is necessary to administrate
      high-effective anti-HBV drug prior to glucocorticoid treatment in order to
      prevent liver failure.

PMID- 30113455
TI  - Effects of nonvalvular atrial fibrillation on the structure and function of
      mitral valves (a STROBE-compliant article).
AB  - The aim of this study was to explore the effects of nonvalvular atrial
      fibrillation (NVAF) on the structure and function of mitral valve and analyze
      independent risk factors of moderate to severe mitral regurgitation (MR) by
      quantitative measurement of mitral parameters using real-time 3-dimensional
      transesophageal echocardiography.This study included 30 subjects with sinus
      rhythm group, and 65 patients with NVAF. The 65 patients with NVAF were divided
      into 35 with paroxysmal atrial fibrillation group and 30 with persistent atrial
      fibrillation. According to MR degree, the patients with NVAF were again divided
      into no or mild MR group (n = 44) and moderate to severe MR group (n = 21).There
      were significant differences in anterolateral-to-posteromedial diameter (DAlPm),
      anterior-to-posterior diameter, 3-dimensional circumference (C3D), 2-dimensional
      area (A2D), mitral leaflet surface area in late systolic phase, the index of
      mitral valve coaptation and left atrial internal diameter (LAID) between
      different cardiac rhythm groups (all P < .05). The DAlPm, C3D, A2D, nonplanar
      angle (thetaNPA), and LAID were greater but the mitral valve coaptation index was
      smaller in the moderate to severe MR group than in the no or mild MR group (all P
      < .05). Logistic regression analysis indicated that DAlPm and LAID were
      independent risk factors of moderate to severe MR in the patients with NVAF (OR >
      1, P < .05).DAlPm and LAID are independent risk factors of moderate to severe MR
      in the patients with NVAF. NVAF can change the structure and function of mitral
      valve, which leads to MR.

PMID- 30113454
TI  - Novel frame shift mutation in ERCC6 leads to a severe form of Cockayne syndrome
      with postnatal growth failure and early death: A case report and brief literature
      review.
AB  - INTRODUCTION: Cockayne syndrome (CS) is a rare multisystemic autosomal recessive
      disease. The primary manifestations of which are developmental delay,
      neurological impairment, abnormal skin sensitivity to sunlight and unique facial
      appearance as sunken eyes, large ears, and thin large nose. The disorders of the
      nucleotide excision repair system significantly are caused by mutations of
      Excision repair cross-complementing group 6 (ERCC6) and Excision repair cross
      complementing group 8 (ERCC8) genes, and the ERCC6 gene mutations are present in
      approximately 65% of cases. CASE PRESENTATION: Here we described a girl in a
      consanguineous Jordanian family with abnormal facial appearance and postnatal
      growth delay. She was not able to gain weight. Her condition deteriorated
      progressively and she developed difficulty of swallowing even to water. The
      patient was diagnosed as CS based on her facial appearance and neurologic
      dysfunction. The patient was examined at 3 years old, and died at 4 years old.
      CONCLUSION: Genetic analysis and sequencing revealed homozygosity for a novel
      frame shift mutation c.2911_2915del5ins9 (p.Lys971TryfsX14) in the ERCC6. The
      mutation is predicted to delete 5 nucleotides and add 9 nucleotides with a
      premature termination, resulting in approximately 34% length reduction of the
      wild-type transcript. The multisystem malformations of CS are clinically
      heterogeneous. The frame shift mutation of ERCC6 found in this patient is a novel
      one, which caused postnatal growth failure and early death. Our findings indicate
      truncated mutation in CS lead to more severe CS phenotype and add to the genotype
      phenotype correlations in CS.

PMID- 30113456
TI  - Perforation caused by gastric mucosa associated lymphoid tissue lymphoma: A case
      report and literature review.
AB  - RATIONALE: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the most
      common and best-studied extranodal marginal zone lymphoma of the MALT. It is
      characterized by an indolent clinical course and excellent survival compared with
      other malignant tumor. Complications such as obstruction, perforation or bleeding
      are rarely observed. The treatment strategy is still controversial. PATIENT
      CONCERNS: A 59-year-old man, who had been diagnosed with MALT lymphoma by
      gastroscopy and biopsy one month before, came to the hospital for a sudden onset
      of abdominal pain after breakfast. DIAGNOSES: MALT lymphoma; gastric perforation.
      INTERVENTIONS: Emergency surgery. OUTCOMES: Gastric perforation repair and
      jejunostomy was performed. The patient recovered well and is preparing for
      combined chemotherapy. LESSONS: This case report illustrates the challenges in
      diagnosis and treatment of MALT lymphoma. We discussed the particularity of its
      clinical characteristics, treatment strategies and prognosis combined with
      literature review, and we think that early diagnosis and timely appropriate
      chemotherapy is of great importance.

PMID- 30113457
TI  - Imaging features and differential diagnosis of multiple diaphyseal sclerosis: A
      case report and review of literature.
AB  - RATIONALE: Multiple diaphyseal sclerosis (MDS), known as Ribbing disease, is a
      rare congenital bone disease resulting from autosomal recessive inheritance. The
      case study involved a 22-year-old female patient who had been diagnosed with
      chronic sclerosing osteomyelitis due to lack of knowledge about MDS. Previous
      studies reported rarely on this condition. PATIENT CONCERNS: A 22-year-old female
      with MDS was analyzed. DIAGNOSES: MDS is characterized radiographically by a
      fusiform widening of the diaphyseal portion of the long bones, which is caused by
      a thickening of the cortex with obstruction of the medullary cavity. The
      pathologies are observed utilizing diagnostic imagery and are often difficult to
      identify. INTERVENTION: The patient was following a suggested regimen of oral
      celecoxib capsules at 200 mg/day for 6 days. OUTCOMES: The patient's diagnosis
      was revised to the rare condition of Ribbing disease by reviewing the clinical
      history and distinctive radiography images and because the symptoms were
      alleviated by celecoxib capsule. We also present a review of the literature on
      the diagnosis and differential diagnosis of MDS based on clinical and imaging
      features. LESSONS: MDS is rare and may often be initially misdiagnosed as another
      type of sclerosing bone dysplasia, thus, it is important to be aware of the
      existence of MDS. Once MDS is suspected, differential diagnosis should be
      performed to exclude other sclerosing bone dysplasias, taking into account
      clinical history, distinctive radiographic appearance, distribution, and
      laboratory and histopathologic findings. Laboratory evaluation and pathologic
      findings are nonspecific but assist in excluding other diagnoses. More evidence
      is needed to illustrate the effectiveness of medical or surgical treatments for
      patients with MDS.

PMID- 30113458
TI  - Multidrug-resistance Acinetobacter baumannii pneumonia in a rheumatoid arthritis
      patient receiving tumor necrosis factor inhibitor: A case report.
AB  - INTRODUCTION: Multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia with
      severe sepsis in a patient with rheumatoid arthritis (RA), who is predisposed
      after treatment with tumor necrosis factor inhibitor (TNFI), is a rare severe
      infection and can be successfully treated with prompt antibiotics. CASE
      PRESENTATION: A 75-year-old woman was diagnosed with RA >30 years previously.
      After inadequate treatment responses to conventional disease-modifying
      antirheumatic drugs (DMARDs), she developed progressive RA, including swollen
      joints in both hands, and had a high disease activity score of 4.96 when
      presenting at our rheumatology clinic. She had started taking the TNFI, golimumab
      (50 mg/month), 3 years before and developed a productive cough 4 weeks before
      this admission. One week after admission, she developed fever, dyspnea,
      hypoxemia, tachycardia, and increased serum C-reactive protein level. DIAGNOSIS:
      Chest plain film (CxR) and computed tomography of the chest showed hospital
      acquired pneumonia; microbial examination of the sputum showed the presence of
      MDRAB. THERAPEUTICS: She was prescribed a full course of antibiotics with
      cefoperazone sulbactam. OUTCOMES: CxR showed complete remission of pneumonia.
      CONCLUSION: Biological DMARDs, such as TNFI, act as a double-edged sword: these
      drugs are used to treat autoimmune diseases, but they increase the risk of
      infection. The trend toward antibiotic resistance and persistent environmental
      survival of MDRAB is an emerging problem in countries with high rates of
      antibiotic abuse. TNFI may affect intestinal immunity by inducing dysbiosis,
      which affects T helper 17-mediated mucosal immunity and can contribute to A
      baumannii colonization and the development of MDRAB in frequently hospitalized
      patients.

PMID- 30113459
TI  - Intracerebral hemorrhage in an adult patient with Tetralogy of Fallot: Case
      report and review of the literature.
AB  - RATIONALE: Tetralogy of Fallot (TOF) accounts for approximately 5% of all
      congenital heart disease. However, only 1% of patients with TOF survive to the
      age of 40 years without undergoing surgery. Additionally, the relationship
      between intracerebral hemorrhage and unrepaired TOF remains unknown. We report a
      rare case of unrepaired TOF in a patient who presented with intracerebral
      hemorrhage, and we also present a literature review. PATIENT CONCERNS: A 40-year
      old man presented with headache and right-sided limb weakness. DIAGNOSES: He was
      diagnosed with TOF approximately a year prior to presentation and did not undergo
      any definitive treatment or any symptomatic management. Head computed tomography
      revealed an intracerebral hematoma in the left basal ganglia. The patient was
      drowsy, and his blood oxygen saturation was 77%. INTERVENTIONS: Owing to his poor
      cardiopulmonary status, the patient did not undergo surgery and was treated with
      only symptomatic supportive therapy. OUTCOMES: After 2 days of therapy, his
      disturbance of consciousness and motor ability showed improvement. LESSONS:
      Literature reviews reveal that intracerebral hemorrhage is rarely observed in
      patients with TOF, and to date, only 3 cases have been reported. Furthermore,
      this patient was 40 years old and did not undergo cardiac surgery. Severe
      hypoxia, as well as low levels of platelets and coagulation factors in the blood
      could have led to intracerebral hemorrhage.

PMID- 30113460
TI  - A retrospective cohort study of risk factors and pregnancy outcomes in 14,014
      Chinese pregnant women.
AB  - This study aims to investigate major complications or symptoms of pregnant women,
      causes of maternal near-miss, and issues that are relevant to severe maternal
      disease.A retrospective analysis was performed in the "maternal individual
      investigation form," which included all critical maternity patients admitted to
      the First Affiliated Hospital of Anhui Medical University from January 1, 2012 to
      September 31, 2015.A total of 14,014 pregnant patients who delivered at 28 to 42
      weeks of gestation were included. Eight thousand eighty-six patients experienced
      complications or symptoms, and top 7 of these were postpartum hemorrhage,
      hypertension during pregnancy, diabetes, anemia, hepatopathy, nephroma, and
      connective tissue disease, of which the morbidity were 11.92%, 10.15%, 9.34%,
      8.57%, 3.13%. 0.56%, and 0.55%, respectively. Delivery times, gestational weeks,
      and informal pregnancy examinations had significant correlation with maternal
      near-miss (P < .05); nevertheless, the age at pregnancy, number of pregnancies,
      and education were not so significant (P > .05). Two hundred sixty-five patients
      had severe maternal diseases (maternal near miss), and the top 5 causes for
      severe maternal morbidity were massive blood transfusion, thrombocytopenia,
      clinical feature of shock, uterus removal induced by uterus infection or
      bleeding, and coagulation dysfunction, of which the morbidity were 24.15%,
      18.87%, 13.58%, 9.43%, and 6.79%, respectively.Delivery times, gestational weeks,
      and informal pregnancy examinations should be considered in maternal near miss
      patients. Moreover, hypertensive disorders during pregnancy, postpartum
      hemorrhage, anemia, thrombocytopenia, hepatopathy, and cardiopathy were the
      principal causes of maternal near miss. Therefore, the monitoring of these
      principal causes of severe maternity near miss is important for reducing the
      maternal morbidity and mortality.

PMID- 30113461
TI  - Sexual behavior across the transition to adulthood and sexually transmitted
      infections: Findings from the national survey of human papillomavirus prevalence
      (POP-Brazil).
AB  - The sexual behaviors of 15- to 24-year-olds increase the risk of this population
      to acquire sexually transmitted infections (STIs). The present study aimed to
      describe the sexual behavior in the transition to adulthood Brazilian population
      and its association with STI history.We analyzed cross-sectional data collected
      from 8562 sexually active women and men who participated in the National Survey
      of Human Papillomavirus Prevalence (POP-Brazil). This large-scale survey enrolled
      participants from 26 Brazilian capitals and the Federal District. Professionals
      from primary care facilities were trained to collect data utilizing a
      standardized questionnaire with questions on sociodemographic, sexual behavior,
      and drug use. We constructed a Poisson model with robust variance for both crude
      and adjusted analysis to investigate the associations between the variables. To
      adjust the distribution of the sample to the study population, we weighted the
      measures by the population size in each city and by gender.There were differences
      in several aspects from sexual behavior between genders. The majority of men
      reported an early sexual initiation, more sexual partners, and a different
      practice in sexual positions when compared with women. Women reported use of
      contraception more frequently than men (P < .001). The use of alcohol and drugs
      and the use of drugs before sexual intercourse impact in STIs equally between the
      genders. Exclusive for women, the presence of any STI was associated with the
      practice of vaginal sex and other types of intercourse (adjusted prevalence ratio
      [APR] 1.43, 95% CI 1.08-1.88). For men, the number of sexual partners in the last
      year (APR 1.02, 95% CI 1.01-1.04), not having vaginal sex (APR 3.25, 95% CI 1.78
      5.92) and sexual experience with someone of the same sex (APR 4.05, 95% CI, 2.88
      5.70) were associated with a higher presence of STIs.This is the first report
      regarding sexual behavior in a nationally representative population sample in
      Brazil. This study provides more valid estimates of sexual behavior and
      associated STIs, identifying important differences in sexual behavior and
      identifying predictors for referred STIs among females and males.

PMID- 30113462
TI  - Spontaneous expulsion of a huge cervical leiomyoma from the vagina after
      cesarean: A case report with literature review.
AB  - RATIONALE: As more and more women delay their child bearing age, the prevalence
      of uterine fibroids during pregnancy is likely to increase. PATIENT CONCERNS &
      LESSONS: We report a Chinese Tibetan case with spontaneous expulsion of a huge
      cervical myoma after cesarean. Decreased blood supply of the myoma and the
      uterine contraction may contribute to the spontaneous expulsion. Vaginal
      myomectomy is recommended as the initial treatment.

PMID- 30113463
TI  - Association between -174G>C polymorphism in the IL-6 promoter region and the risk
      of obesity: A meta-analysis.
AB  - BACKGROUND: Many researchers have suggested that the -174G>C polymorphism in the
      interleukin-6 (IL-6) promoter region contributes to the risk of obesity; however,
      this hypothesis is still inconclusive. Therefore, we conducted a meta-analysis to
      combine the data from several studies to arrive at a conclusion regarding the
      association between -174G>C polymorphism and the risk of obesity. METHODS: The
      PubMed and Embase databases were searched up to February 20, 2018. The odds
      ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using a
      random-effects model. Subgroup analysis and sensitivity were also performed.
      RESULTS: Ten eligible studies involving 7210 cases were performed to identify the
      association strength. The association strength was measured by the ORs and 95%
      CIs. By pooling the eligible studies, we found a significant association between
      the -174G>C polymorphism and obesity risk (C vs G: OR = 1.37; 95% CI, 1.08-1.74;
      Pheterogeneity < .01). Overall, individuals with the variant CC (OR = 1.58; 95%
      CI, 1.09-2.28; Pheterogeneity < 0.01) and GC/CC (OR = 1.61; 95% CI, 1.13-2.29;
      Pheterogeneity < .01) were associated with a significantly increased risk of
      obesity. CONCLUSION: The meta-analysis results suggested that the polymorphism 
      174G>C in the IL-6 promoter region was associated with a significantly increased
      risk of obesity.

PMID- 30113464
TI  - Stereotactic radiosurgery (SRS) alone versus whole brain radiotherapy plus SRS in
      patients with 1 to 4 brain metastases from non-small cell lung cancer stratified
      by the graded prognostic assessment: A meta-analysis (PRISMA) of randomized
      control trials.
AB  - BACKGROUND: The present study aims to assess the therapeutic effect of whole
      brain radiotherapy (WBRT) for brain metastases from non-small cell lung cancer
      stratified by graded prognostic assessment (GPA) through meta-analysis. METHODS:
      The Cochrane Library, PubMed, Ovid (Elsevier) were retrieved. The included
      randomized controlled trials (RCT) were evaluated, and the statistical analysis
      was performed using RevMan 5.3 software. Cochrane handbook was applied to
      evaluate the methodological quality. Statistical significance was considered as P
      < .05. RESULTS: There were 2 randomized control trials identified eligible for
      the meta-analysis. Stereotactic radiosurgery (SRS)+WBRT did not significantly
      improved overall survival (OS) in 2 subgroups. (GPA <2: HR, 0.93; 95% confidence
      interval [CI], 0.61-1.40; P = .71), (GPA >=2: HR, 1.28; 95% CI, 0.58-2.80; P =
      .54). The use of SRS+WBRT significantly extended brain tumor recurrence (BTR)
      free time in both subgroups (GPA <2: HR, 5.46; 95% CI: 2.09-14.22; P = .0005),
      (GPA >=2: HR, 4.24; 95% CI: 2.24-8.04; P < .00001). The meta-analysis showed
      salvage therapy was more frequent among the SRS-alone in 2 subgroups (GPA <2: RR,
      5.83; 95% CI: 1.47-23.06; P = .01), (GPA >=2: RR, 2.53; 95% CI: 1.30-4.93; P =
      .006). The rate of grade 3 or 4 late radiation toxic effects was similar in 2
      subgroups between SRS and SRS+WBRT CONCLUSIONS:: Because there are few studies to
      meet inclusion criteria, we cannot include more researches. The results of this
      analysis must be carefully interpreted in view of the unclear risk of bias in
      inclusion in the study. This meta-analysis of 2 randomized trails indicated that
      the combined treatment group did not show a survival benefit over SRS alone.
      However, SRS+WBRT improved BTR free time in the subgroup both GPA <2 and GPA >=2
      with the similar grade 3 or 4 late radiation toxicities.

PMID- 30113465
TI  - Intestinal fatty acid-binding protein as a predictor of prognosis in
      postoperative cardiac surgery patients.
AB  - During the perioperative period of cardiac disease, as many risk factors exist,
      such as primary cardiac diseases, the use of vasopressors, ischemia-reperfusion
      injury during cardiopulmonary bypass (CPB), and surgical stress, the gut suffered
      from ischemia, anoxia and oxidative stress, which would lead to the enterocyte
      injury. The aim of this study was to explore whether serum intestinal fatty acid
      binding protein (IFABP), which is excreted specifically from damaged intestinal
      enterocytes, as a predictor of prognosis in postoperative cardiac surgery
      patients.From January 2017 to December 2017, 40 postoperative cardiac surgery
      patients were enrolled in this observational study. Serum IFABP levels and
      prognostic biomarkers were recorded at intensive care unit (ICU) admission.The
      serum IFABP levels were significantly higher in postoperative cardiac surgery
      patients who complicated with multiple organ dysfunction syndrome (MODS) (median,
      883.20 pg/mL vs 426.10 pg/mL; P < .001), infective complications (median, 917.70
      pg/mL vs 409.40 pg/mL; P < .001), or who stayed in ICU beyond 4 days (median,
      807.65 pg/mL vs 426.10 pg/mL; P < .001). Moreover, in patients who suffered from
      right ventricular dysfunction, the serum IFABP levels were significantly higher
      (median, 737.85 pg/mL vs 445.55 pg/mL; P = .016). The serum IFABP levels also
      showed great precision for the prediction of MODS (the area under curve, AUC
      0.923), infective complications (AUC 0.961) and ICU stay beyond 4 days (AUC
      0.853). And it correlated significantly with the acute physiology and chronic
      health evaluation (APACHE) II score (P < .05), sequential organ failure
      assessment (SOFA) score (P < .05), and acute gastrointestinal injury (AGI) grade
      (P < .001).The serum IFABP level at ICU admission is a valuable, convenient, and
      objective early predictor of prognosis in postoperative cardiac surgery patients.

PMID- 30113466
TI  - Effect of reducing assistance during robot-assisted gait training on step length
      asymmetry in patients with hemiplegic stroke: A randomized controlled pilot
      trial.
AB  - BACKGROUND: An assist-as-needed robot-assisted gait training protocol was
      recently developed. It allows active movement during training, but its exact
      criteria remain unknown. Asymmetric step length is a common abnormal gait pattern
      in hemiplegic stroke patients. We compared the effects of assist-as-needed robot
      assisted gait training on the unaffected and affected limbs of hemiplegic stroke
      patients. METHOD: Twenty-four chronic stroke patients with asymmetric step
      lengths were randomly assigned to 1 of 2 groups. Twelve completed the study
      protocol. Group 1 underwent 20 sessions of assist-as-needed robot-assisted gait
      training for the unaffected limb and fully-assisted robot-assisted training for
      the affected limb. Group 2 underwent 20 sessions of robot-assisted gait training
      using the opposite protocol. Clinical measurements were obtained and 3
      dimensional gait analyses were performed at baseline and after 10 and 20 training
      sessions. RESULTS: Clinical measurements improved in both groups after 20
      training sessions. The unaffected limb's step length asymmetry ratio and hip
      maximal extension moment significantly improved in group 1. The affected limb's
      maximal dorsiflexion angle for the ankle in the swing phase significantly
      improved in group 2. CONCLUSION: Application of the assist-as-needed training
      mode for the unaffected limb helped improve step length asymmetry in chronic
      stroke patients.

PMID- 30113468
TI  - Pathologic outcomes of endoscopic submucosal dissection for gastric epithelial
      neoplasia.
AB  - Endoscopic submucosal dissection (ESD) has been widely implemented for the
      treatment of gastric superficial neoplasia. However, the final pathologic
      diagnosis after ESD may be different from that indicated by the results of
      endoscopic forceps biopsy. This study identified risk factors for gastric
      epithelial lesions so that early gastric cancer (EGC) could be diagnosed after
      ESD.From December 2008 to January 2017, 1541 lesions (1410 patients) diagnosed as
      initial adenoma or indefinite for neoplasia by endoscopic forceps biopsy were
      enrolled. The EGC rate and factors predicting upstaged diagnoses were analyzed
      retrospectively.The diagnostic discrepancy rate was 31.1%. Upstaged and
      downstaged diagnostic rates after ESD were 23.8% and 7.3%, respectively. The
      upstaged diagnosis rate for EGC was 18.8%. Gross depression (OR, 16.017) and
      surface redness (OR, 22.136) were significantly associated with EGC and lesions
      indefinite for neoplasia during the initial endoscopic forceps biopsy. Central
      depression (OR, 2.959), nodular surface (OR, 6.581), and surface redness (OR,
      6.399) were significantly associated with EGC and lesions with low-grade
      dysplasia during the initial endoscopic forceps biopsy. Central depression (OR,
      1.999), nodular surface (OR, 1.733), surface redness (OR 2.283), lesion location
      (upper third of the stomach) (OR, 3.989), and tumor size >=10 mm (OR, 2.200) were
      significantly associated with EGC and lesions with high-grade dysplasia during
      the initial endoscopic forceps biopsy.Central depression, nodular surface,
      surface redness, lesion location, and tumors >10 mm were associated with EGC.
      Gastric epithelial lesions with these characteristics require attention before
      ESD.

PMID- 30113467
TI  - Bacteriuria and asymptomatic infection in chronic patients with indwelling
      urinary catheter: The incidence of ESBL bacteria.
AB  - Urinary tract infections due to the presence of a urinary catheter represent a
      real problem for patients who have to carry such an invasive device for a long
      time.Our aim was to identify the susceptibility of extended spectrum beta
      lactamases (ESBL) versus non-ESBL bacteria to antibiotics in urinary tract
      infections in patients who are chronic carriers of urinary catheters.The
      retrospective study included a period of 5 years, a total of 405 patients who are
      chronic carriers of urinary catheters, admitted to rehabilitation and palliative
      care units.Escherichia coli (E coli) was isolated in 41.2% of patients,
      Klebsiella pneumoniae (K pneumoniae) in 24.7%, and Proteus mirabilis (P
      mirabilis) in 15.3%. E coli microbial resistance rates ranged from a minimum of
      7.5% (nitrofurantoin) to a maximum of 77.1% (ampicillin). In the case of K
      pneumoniae, microbial resistance ranged from 34.2% (netilmicin) to 73.2%
      (ceftriaxone). Resistance rates of P mirabilis ranged from 11.1% (cefepim) to
      89.5% (ampicillin). Positivity of ESBL bacteria was identified in 47.4% of
      patients. Resistance rates of ESBL-positive E coli ranged from 50.0%
      (ceftriaxone) to 88.1% (cefepime), and ESBL-negative E coli rates ranged from
      3.4% (cefepime) to 64.4% (amikacin). Resistance rates of ESBL-positive K
      pneumoniae ranged between 39.1% (netilmicin) and 85.1% (ceftriaxone), and ESBL
      negative K pneumoniae between 7.1% (cefepime) and 53.3% (amikacin). In cases of
      ESBL-positive P mirabilis, rates ranged from 13.3% (cefepime) to 90.3%
      (ceftriaxone), whereas in cases of ESBL-negative P mirabilis, rates ranged
      between 8.3% (cefepime) and 80.0% (trimetroprim).Bacteriuria and asymptomatic
      catheter infection in chronic carriers is an important public health concern due
      to the frequent presence of multidrug-resistant bacteria. Our study highlights
      the need to develop control programs of catheter infections to minimize the risk
      of infections associated with these medical devices, and also the need for
      treatment of the infection rather than catheter colonization or contamination.

PMID- 30113469
TI  - Cognitive decline and white matter changes in mesial temporal lobe epilepsy.
AB  - Noninvasive imaging plays a pivotal role in assessing the brain structural and
      functional changes in presurgical mesial temporal lobe epilepsy (MTLE) patients.
      Our goal was to study the relationship between the changes of cerebral white
      matter (WM) and cognitive functions in MTLE patients.Voxel-based morphometry
      (VBM) and tract-based spatial statistics (TBSS) MRI were performed on 24 right
      handed MTLE patients (12 with left MTLE and 12 with right MTLE) and 12 matching
      healthy controls. Gray matter (GM), WM, and whole brain (WB) volumes were
      measured with VBM while fractional anisotropy (FA), mean diffusivity (MD), axial
      diffusivity (AD), and radial diffusivity (RD) were measured with TBSS. All
      patients and controls also underwent Montreal Cognitive Assessment (MoCA) before
      MRI.WM volume and the ratio of WM volume versus WB volume were significantly
      lower in MTLE patients compared with controls. WM volume in MTLE patients had a
      positive correlation with MoCA score (r = 0.71, P < .001) and a negative
      correlation with the duration of epilepsy (r = -0.693, P < .001). Volumetric
      differences were mainly located in the corpus callosum, uncinate fasciculus,
      inferior longitudinal fasciculus, and superior longitudinal fasciculus. FA of
      both left MTLE and right MTLE groups was significantly decreased, while MD, AD,
      and RD were significantly increased. Most left MTLE patients showed bilateral WM
      fiber tract changes versus ipsilateral changes for right MTLE patients.Changes in
      DTI parameters and WM volume were found in MTLE patients and more ipsilateral
      changes were seen with right-sided MTLE. Cognitive changes of MTLE patients were
      found to be correlated with the changes in WM structure. These findings not only
      provide useful information for lateralization of the seizure focus but can also
      be used to explain functional connectivity disorders which may be an important
      physiological basis for cognitive changes in patients with MTLE.

PMID- 30113471
TI  - Burr hole drainage and burr hole drainage with irrigation to treat chronic
      subdural hematoma: A systematic review and meta-analysis.
AB  - OBJECTIVE: Numerous studies have investigated different operative procedures for
      treating chronic subdural hematoma (CSDH); however, the results are
      controversial. This meta-analysis was performed to evaluate the efficacy of burr
      hole drainage without irrigation (BHD) and burr hole drainage with irrigation
      (BHDI) for CSDH. METHODS: We searched the following electronic databases to
      identify all studies from their inception to September 2017: Cochrane Library,
      Science Direct, MEDLINE, EMBASE, Scopus, Google Scholar, the China Biomedical
      Database (CBM), and the Chinese National Knowledge Infrastructure (CNKI).
      Randomized clinical trials (RCTs), prospective cohort studies, retrospective
      observational cohort studies, and case-control studies investigating BHD and BHDI
      for the treatment of CSDH were included. The Cochrane Collaboration's RevMan 5.3
      software was used for meta-analysis. RESULTS: In total, 7 retrospective cohort
      studies and 2 RCTs involving 993 participants were included. Comprehensive
      analysis results of 9 studies indicated that the recurrence of the BHDI was
      similar to that in BHD (odds ratio [OR] = 1.27, 95% confidence interval [CI] =
      .61-2.63, P = .53). Moreover, analysis for comparing recurrence in the 2 RCTs was
      not significantly different (OR = 1.14, 95% CI = .16-8.24, P = .95).In addition,
      meta-analysis of pneumocephalus (OR = 5.91, 95% CI = .61-56.86, P = .12) and
      mortality (OR = 0.94, 95% CI 0.14-6.16, P = .95) was not significantly different.
      CONCLUSIONS: The results of this meta-analysis demonstrated that procedures with
      or without irrigation in the treatment of CSDH might have similar effect
      regarding recurrence and complications; therefore, irrigation might not be
      necessary. However, well-conducted RCTs and high-quality observational studies
      are still required to corroborate this issue.

PMID- 30113470
TI  - Potential role of contrast-enhanced ultrasound for the differentiation of
      malignant and benign gallbladder lesions in East Asia: A meta-analysis and
      systematic review.
AB  - BACKGROUND: The purpose of this study was to systematically review and evaluate
      the diagnostic accuracy of contrast-enhanced ultrasound (CEUS) in differentiating
      malignant and benign gallbladder lesions. METHODS: We conducted a comprehensive
      search on PubMed, Embase, and Cochrane Library for all potential relevant
      articles published before December 2017. The pooled sensitivity, specificity,
      diagnostic odds ratio (DOR) and area under the curve (AUC) of summary receiver
      operating characteristic (SROC) were calculated by Meta-Disc Version 1.4 and
      STATA 12.0. RESULTS: Twelve eligible studies were included in our study. A total
      of 1044 patients were assessed. The pooled sensitivity and specificity were 0.81
      (95% confidence interval [CI], 0.77-0.84; inconsistency index [I] = 84.5%) and
      0.87 (95% CI, 0.85-0.89; I = 94.4%), respectively. The pooled DOR was 58.84 (95%
      CI, 32.39-106.88; I = 51.9%). The AUC was 0.9371. According to Deek funnel plot
      asymmetry test, there was no significant publication bias (P = .31). CONCLUSIONS:
      The results yielded from the available evidence suggest that CEUS is a promising
      and adjuvant imaging technique to conventional ultrasound for the differential
      diagnosis of benign and malignant gallbladder lesions.

PMID- 30113472
TI  - Clinical relevance of point mutations in the 23S rRNA gene in Helicobacter pylori
      eradication: A prospective, observational study.
AB  - Clarithromycin-based triple therapy is prescribed worldwide for Helicobacter
      pylori eradication. However, increases in the clarithromycin resistance of H
      pylori are thought to be responsible for eradication failure. Here, we studied
      whether point mutations in domain V of the 23S rRNA gene can affect H pylori
      eradication failure in a prospective, open-label, observational study. Of the 755
      enrolled patients, 299 patients (39.6%) had positive Campylobacter-like organism
      (CLO) tests. DNA sequencing analysis of H pylori 23S rRNA in 295 patients
      revealed that 2143G was the most frequent point mutation (24.7% of patients),
      followed by the 2182T mutation (11.5%). The overall eradication failure rate was
      20.9% (42/201) in clarithromycin-based triple therapy. Patients with the 2143G
      had an approximately 60% eradication failure rate, which suggested that 2143G was
      a high-risk genotype for eradication failure. Patients with the 2182C genotype
      without 2143G had an 8.7% failure rate, and patients without 2143G or 2182C had
      only a 4.3% failure rate. The presence of 2143G, which was associated with
      previous eradication history and female sex, was an independent risk factor for
      eradication failure. In conclusion, the 2143G point mutation in the 23S rRNA of H
      pylori was an independent risk factor for eradication failure in clarithromycin
      based triple therapy. Personalized tailored therapy based on the genotypes of 23S
      rRNA can increase eradication success rates in H pylori infections.

PMID- 30113475
TI  - Meta-analysis of the efficacy of Ningmitai capsule on the treatment of chronic
      prostatitis in China.
AB  - BACKGROUND: To evaluate the efficacy and safety of Ningmitai (NMT) capsule for
      treating chronic prostatitis (CP) in China. METHODS: Retrieving the China Journal
      Full-Text Database (CNKI), Wanfang database, China's outstanding
      master's/doctoral dissertation database, VIP Science and Technology Periodical
      Database, Cochrane library, PubMed, Embase, and Chinese academic conference
      papers. Collecting and selecting literatures of randomized controlled trials
      before March 2017 on NMT capsule for CP, evaluated by Jadad scale, and then
      analyzed with Stata software. RESULTS: Thirty randomized clinical trials
      including 6185 patients (3124 in the test group and 3061 in the control group)
      were included. The overall treatment risk ratios (RRs) were 1.19 (1.14, 1.24).
      The merged RRs were 1.05 (0.95, 1.15) and 1.22 (1.19, 1.26) for the single-drug
      group and the combined-drug group, respectively. The adverse events were found to
      be lower in all groups. CONCLUSION: NMT is effective and safety on the treatment
      of CP, especially in combined-drug groups. High quality and a good design of
      multicentered, randomized, parallel-controlled and blinding trials are needed in
      order to make further studies, and deserve further examination for the treatment
      of CP with NMT.

PMID- 30113473
TI  - Ovarian yolk sac tumor in postmenopausal females: A case series and a literature
      review.
AB  - RATIONALE: Ovarian yolk sac tumors (YSTs) are the second most common histologic
      type of ovarian germ cell tumors. Most patients are adolescent and young women,
      while cases in postmenopausal women were rarely reported. Due to its rarity, we
      know little about the treatment and prognosis of postmenopausal patients with
      ovarian YSTs. We reported 3 cases of mixed ovarian YST in postmenopausal females
      reviewed the related current English literature. PATIENT CONCERNS: The ages of
      the three patients were 61, 58 and 77 respectively. The three patients came to
      the hospital because of the abdominal discomfort or tenderness, and the third
      patient also has vaginal bleeding. DIAGNOSES: Imaging examination revealed pelvic
      mass with cystic and solid components. The elevated serum AFP level and
      pathologcial examination confirmed mixed ovarian YST. INTERVENTIONS: All patients
      received surgery and chemotherapy. Two patients received PEB (cisplatin,
      etoposide, and bleomycin) chemotherapy initially and one patient received TC
      (paclitaxel carboplatin) chemotherapy. OUTCOMES: One patient relapsed 8 months
      after diagnosis and underwent re-cytoreductive surgery. The three patients all
      survived at last follow-up. LESSONS: The diagnosis of postmenopausal ovarian YST
      is relatively difficult and it can coexist with other germ cell or epithelial
      tumors. Postmenopausal ovarian YSTs are aggressive, and may have a worse
      prognosis compared with those in young patients. More aggressive treatment is
      needed. When YST mixed with epithelial cancer components, adjuvant chemotherapy
      regimen should include platinum-based chemotherapy aiming at both epithelial
      ovarian cancer and germ cell tumors.

PMID- 30113474
TI  - Fifteen-gene expression based model predicts the survival of clear cell renal
      cell carcinoma.
AB  - Clear-cell renal cell carcinoma (ccRCC) is the major renal cell carcinoma
      subtype, but its postsurgical prognosis varies among individual patients.We used
      gene expression, machine learning (random forest variable hunting), and Cox
      regression analysis to develop a risk score model based on 15 genes to predict
      survival of patients with ccRCC in the The Cancer Genome Atlas dataset (N = 533).
      We validated this model in another cohort, and analyzed correlations between risk
      score and other clinical indicators.Patients in the high-risk group had
      significantly worse overall survival (OS) than did those in the low-risk group (P
      = 5.6e-16); recurrence-free survival showed a similar pattern. This result was
      reproducible in another dataset, E-MTAB-1980 (N = 101, P = .00029). We evaluated
      correlations between risk score and other clinical indicators. Risk was
      independent of age and sex, but was significantly associated with hemoglobin
      level, primary tumor size, and grade. Radiation therapy also had no effect on the
      prognostic value of the risk score. Cox multivariate regression showed risk score
      to be an important indicator for ccRCC prognosis. We plotted a nomogram for 3
      year OS to facilitate use of risk score and other indicators.The risk score model
      based on expression of the 15 selected genes can predict survival of patients
      with ccRCC.

PMID- 30113476
TI  - Reduction in the incidence of pneumonia in elderly patients after hip fracture
      surgery: An inpatient pulmonary rehabilitation program.
AB  - Hip fracture is an important health care issue in the elderly. Postoperative
      pulmonary complications occur in 4% of patients after hip fracture surgery.
      However, previous research is limited regarding pulmonary rehabilitation in this
      group. In this study, we present clinical evidence regarding the impact of a
      comprehensive pulmonary rehabilitation program in elderly hip fracture patients
      after hip surgery.We designed a nonrandomized, Quasi-experimental study,
      comparing 2 sequential time periods in the same center. Elderly patients (>=65
      years) with a new hip fracture from February 1, 2014 to December 31, 2015 and who
      were willing to undergo a postoperative pulmonary rehabilitation program were
      enrolled. The pulmonary rehabilitation program started on January 1, 2015.
      Patients who refused rehabilitation or did not receive a surgical intervention
      were excluded. Patients received either standard care (standard care group) or
      standard care plus the postoperative rehabilitation program (intervention
      group).A total of 240 patients (163 women and 77 men) were enrolled, including
      138 in the standard care group and 102 in the intervention group. The
      intervention group had a significantly lower incidence of pneumonia (6 patients,
      5.9%) compared to the standard care group (19 patients, 13.9%). An age >80 years,
      cancer status, and not undergoing the postoperative pulmonary rehabilitation
      program were factors associated with a higher risk of pneumonia. In multivariate
      analysis, age >80 years, history of stroke/cancer, thrombocytopenia, and
      hyperglycemia (>200 mg/dL) were identified as risk factors for pneumonia.The
      incidence of pneumonia was lower in the elderly patients with hip fractures who
      received the postoperative pulmonary rehabilitation program after surgery. This
      is the first trial to demonstrate the effect of a postoperative pulmonary
      rehabilitation program in hip surgery patients.

PMID- 30113477
TI  - Preoperative radiologic predictors of successful soft tissue release surgery for
      hip subluxation among cerebral palsy patients: A STROBE compliant study.
AB  - Paralytic hip subluxation is a common problem in children with cerebral palsy.
      Although surgical procedures such as soft tissue release and osteotomy have been
      advocated for its prevention, the exact indications of such procedures remain
      unclear. We attempted to evaluate preoperative radiographic parameters and
      identify prognostic factors in children with cerebral palsy. We retrospectively
      investigated 43 hips in 27 children with cerebral palsy who had undergone soft
      tissue release surgery for hip subluxation. We evaluated the age at the time of
      surgery and the radiographic parameters such as the center-edge angle (CEA), the
      migration percentage (MP), and the acetabular index (AI) at 3 time points:
      preoperation, 1 year after surgery, and at final follow-up. The outcome measure
      was determined by the MP value at final follow-up. Student t test was used to
      compare the quantitative variables between 2 groups (good vs poor outcome). Then
      the multiple regression analysis was applied to determine the prognostic factors
      upon soft tissue release surgery. Children with good outcome exhibited higher CEA
      (average value of -1.43 degrees  vs -13.2 degrees  in those with poor outcome),
      lower MP (53.9% vs 71.3%), and lower AI (28.1 degrees  vs 35.3 degrees ). Upon
      multiple regression analysis, we found that the age at the time of surgery,
      preoperative CEA, and preoperative MP did not appear to be independent prognostic
      factors. The only independent factor that affected prognosis after soft tissue
      release surgery was the preoperative AI. The preoperative AI values <34 degrees 
      were associated with the good outcome with specificity of 87% and sensitivity of
      60% according to the receiver operating characteristic curve analysis. These
      findings indicate that the outcome of soft tissue release surgery can be
      predicted by the preoperative AI value.

PMID- 30113478
TI  - Rhabdomyolysis revisited: Detailed analysis of magnetic resonance imaging
      findings and their correlation with peripheral neuropathy.
AB  - The objective is to evaluate the magnetic resonance imaging (MRI) findings in
      rhabdomyolysis in detail and determine their correlation with the development of
      peripheral neuropathy.Magnetic resonance images for 23 patients with confirmed
      rhabdomyolysis with (n = 11) or without (n = 12) peripheral neuropathy were
      retrospectively reviewed for the signal intensity on T1- and T2-weighted images,
      intramuscular hemorrhage, enhancement pattern, shape and margin in the
      longitudinal plane, edema in the deep fascia and overlying subcutaneous layer,
      multiplicity, and bilateral limb involvement. The collected data were
      statistically analyzed and the relationship between the imaging findings and the
      development of peripheral neuropathy was determined.Abnormal signal intensities
      on T1- or T2-weighted images were observed for all patients except one. Fourteen
      patients (60.9%) showed intramuscular hemorrhage. Stippled enhancement (11/23;
      47.8%) was the most common enhancement pattern. Nineteen patients (86.4%) showed
      a well-defined rectangular shape with a ragged margin in the longitudinal plane.
      The affected muscle volume usually increased (17/23; 73.9%), with edema in the
      deep fascia and the overlying subcutaneous layer (13/23; 56.5%). Multiplicity
      within a muscle, compartment, and limb was observed in 7 (31.8%), 18 (81.8%), and
      16 (72.7%) patients, respectively. Bilateral involvement was observed in 7
      patients (30.4%). Only multiplicity within a compartment showed a statistically
      significant correlation with peripheral neuropathy development.Common MRI
      findings in rhabdomyolysis include intramuscular hemorrhage, stippled
      enhancement, a well-defined rectangular shape with a ragged margin in the
      longitudinal plane, and multiplicity. Multiplicity within a compartment may be a
      predictor of the development of peripheral neuropathy.

PMID- 30113479
TI  - Differentiation of acute cholecystitis from chronic cholecystitis: Determination
      of useful multidetector computed tomography findings.
AB  - The purpose of this study was to determine the diagnostic value of multidetector
      computed tomography (MDCT) imaging findings, to identify the most predictive
      findings, and to assess diagnostic performance in the diagnosis and
      differentiation of acute cholecystitis from chronic cholecystitis.In this
      retrospective study, we enrolled 382 consecutive patients with pathologically
      proven acute or chronic cholecystitis who underwent computed tomography (CT)
      within 1 month before surgery. The CT findings were compared and logistic
      regression analysis was used to identify significant CT findings in predicting
      acute cholecystitis. Diagnostic performance of each CT finding and of combined
      findings was also assessed.Statistically significant CT findings distinguishing
      acute cholecystitis from chronic cholecystitis were increased gallbladder
      dimension (85.5% vs 50.6%, P < .001), increased wall enhancement (61.8% vs 78.9%,
      P = .001), increased wall thickness (67.9% vs 31.1%, P < .001), mural striation
      (64.9% vs 28.3%, P < .001), pericholecystic haziness or fluid (66.4% vs 21.2%, P
      < .001), increased adjacent hepatic enhancement (80.0% vs 32.4%, P < .001), focal
      wall defect (9.2% vs 0, P < .001), and pericholecystic abscess (10.7% vs 0, P <
      .001). Subsequent multivariate logistic regression analysis revealed that
      increased adjacent hepatic enhancement [P = .006, odds ratio (OR) = 3.82],
      increased gallbladder dimension (P = .027, OR = 3.12), increased wall thickening
      or mural striation (P = .019, OR = 2.89), and pericholecystic haziness or fluid
      (P = .032, OR = 2.61) were significant predictors of acute cholecystitis. When 2
      of these 4 CT findings were observed together, the sensitivity, specificity, and
      accuracy for the detection of acute cholecystitis were 83.2%, 65.7%, and 71.7%,
      respectively. When 3 of these 4 CT findings were observed together, the
      sensitivity, specificity, and accuracy were 56.5%, 84.5%, and 74.9%,
      respectively. When none of these 4 CT findings were observed, the negative
      predictive value was 96.4%.Increased adjacent hepatic enhancement, increased
      gallbladder dimension, increased wall thickening or mural striation, and
      pericholecystic fat haziness or fluid were the most discriminative MDCT findings
      for the diagnosis and differentiation of acute cholecystitis from chronic
      cholecystitis.

PMID- 30113481
TI  - Management of greenlight laser plus transurethral resection of prostate for
      elderly men.
AB  - The study is aiming to evaluate the treatment safety and efficacy of greenlight
      laser photovaporization of the prostate (PVP) combined with transurethral
      electrovaporization resection (TUVP) for elderly (>= 70 years) men with lower
      urinary tract symptoms due to benign prostatic hyperplasia (BPH/LUTS) with a
      large prostate volume (>= 80 mL). One hundred twelve BPH/LUTS patients treated
      with PVP were divided into 2 groups according to prostate volume (PV), the
      outcomes of the 2 groups were assessed at 12 months after the operation. Patients
      in the PV >= 80 group (n = 51) had a higher level of maximum detrusor pressure
      (Pdet.max) than those in the PV < 80 group (n = 61) (97.14  +/-  36.68 vs 70.70
      +/- 32.55, P < .001). Pdet.max level of the 2 groups was significantly decreased
      at the end of follow-up. International Prostate Symptom Score questionnaires
      (IPSS) score, maximum flow rate (Qmax), and residual urine volume (PVR) were
      significantly improved in comparison to the preoperative status (P < .001). PVP
      combined with TUVP can significantly improve outcomes (IPSS, Qmax, PVR) and is a
      safe and effective technique for elderly BPH/LUTS patients with a large prostate
      volume.

PMID- 30113480
TI  - The role of NLRP3 inflammasome in stroke and central poststroke pain.
AB  - BACKGROUND: NLRP3 inflammasome plays a prominent role in the pathogenesis and
      progression of many diseases, such as type 2 diabetes mellitus, obesity,
      atherosclerosis, and Alzheimer's disease. However, little knowledge is known
      about the role of NLRP3 inflammasome in central post-stroke pain (CPSP). METHODS:
      We selected relevant studies by searching PubMed, Embase, and Medline from
      inception through February, 2018. We systematically reviewed available
      publications according to the terms "NLRP3 inflammasome" and "stroke" or "central
      post-stroke pain" in the title/abstract field. RESULTS: We reviewed the articles
      and put forward two possible ways for NLRP3 inflammasome in CPSP. One way is that
      NLRP3 activation causes cerebral cortex injure, decreasing descending projection
      fiber to thalamus. Such condition may let GABAergic releases reduce, making the
      ventral basal (VB) neurons excitability increased. Finally, CPSP occur. Another
      way is that NLRP3 inflammasome leads to thalamic lesion and strengthens
      inflammatory response of microglia at the same time. Persistent inflammation
      causes GABAergic alteration in thalamus reticular neurons (TRN) to restrain VB
      interneurons functions, contributing to CPSP. CONCLUSIONS: These possible
      mechanisms will help become knowledgeable about the occurrence CPSP and provide
      potential therapy for CPSP.

PMID- 30113483
TI  - Transarterial chemoembolization extends long-term survival in patients with
      unresectable hepatocellular carcinoma.
AB  - The long-term survival benefit of treating unresectable hepatocellular carcinoma
      (HCC) patients with transarterial chemoembolization (TACE) rather than
      conservative treatment remains controversial. This retrospective case-control
      study evaluated the survival of patients with unresectable HCC treated with TACE,
      relative to that of patients who received best supportive care.From January 2002
      to December 2010, 522 of 2386 consecutive patients with unresectable HCC were
      enrolled. Patients were treated with TACE (n = 347) or best supportive care (non
      TACE; n = 175). A survival analysis compared the survival of the 2 groups, as
      well as only those at Barcelona Clinic Liver Cancer Classification (BCLC)-C and
      Child-Pugh-B (39 TACE, 61 non-TACE).The median follow-up was 5 months (0.15-106
      months).The overall median survival of the TACE group (8.0 months) was
      significantly longer than that of the non-TACE (2.0 months; P <= .01). Of the
      patients at BCLC-C and Child-Pugh-B, the overall median survivals of the TACE and
      non-TACE patients were 6.0 and 2.0 months, respectively (P <= .01); and the 1, 2,
      3, 5, and 8-year overall survival rates were significantly superior in the TACE
      group (P <= .01). For all the patients, the independent predictors of survival
      were treatment modalities, portal vein tumor thrombosis, alpha-fetoprotein, and
      BCLC stage. Regarding the TACE patients, contributors to prognosis were portal
      vein tumor thrombosis, alpha-fetoprotein level, and the number of TACE
      procedures.TACE for unresectable HCC was associated with longer survival compared
      with best supportive care, especially for patients at BCLC-C and Child-Pugh-B.

PMID- 30113482
TI  - Contributions of rare coding variants in hypotension syndrome genes to population
      blood pressure variation.
AB  - Rare variants, in particular renal salt handling genes, contribute to monogenic
      forms of hypertension and hypotension syndromes with electrolyte abnormalities. A
      study by Ji et al (2008) demonstrated this effect for rare loss-of-function
      coding variants in SLC12A3 (NCCT), SLC12A1 (NKCC2), and KCNJ1 (ROMK) that led to
      reduction of ~6 mm Hg for SBP and ~3 mm Hg for DBP among carriers in 2492
      European ancestry Framingham Heart Study (FHS) subjects. These findings support a
      potentially large role for these variants in interindividual variation in
      systolic and diastolic blood pressure (SBP, DBP) in the population. The present
      study focuses on replicating the analyses completed by Ji et al to identify
      effects of rare variants in the population-based Atherosclerosis Risk in
      Communities (ARIC) study.We attempted to replicate the findings by Ji et al by
      applying their criteria to identify putative loss-of-function variants with
      allele frequency <0.001 and complete conservation across a set of orthologs, to
      exome sequencing data from 7444 European ancestry participants of the ARIC
      study.Although we failed to replicate the previous findings when applying their
      methods to the ARIC study data, we observed a similar effect when we restricted
      analyses to the subset of variants they observed.These results simultaneously
      support the utility of exome sequencing data for studying extremely rare coding
      variants in hypertension and underscore the need for improved filtering methods
      for identifying functional variants in human sequences.

PMID- 30113484
TI  - Brown tumor of multiple facial bones associated with primary hyperparathyroidism:
      A clinical case report.
AB  - RATIONALE: Only 4.5% of brown tumors involve facial bones; of these, solitary
      bone involvement is usual. Brown tumors of multiple facial bones are extremely
      rare. Here, we report the case of a brown tumor of multiple facial bones
      initially misdiagnosed as an odontogenic cyst. PATIENT CONCERNS: A pregnant 26
      year-old woman was referred to our hospital with painful swelling of multiple
      facial bones, anemia, urinary calculi, marasmus, and a history of multiple bone
      fractures. Laboratory examination revealed an elevated serum calcium level of
      3.09 mmol/L (normal range: 2.0-2.8 mmol/L) and a low phosphorus level of 0.62
      mmol/L (normal range: 0.81-1.65 mmol/L). The serum alkaline phosphatase
      concentration was 397 IU/L (normal range: 24-82 IU/L) and parathyroid hormone
      level was 267 pg/mL (normal range: 14-72 pg/mL). Cone beam computed tomography
      revealed multiple ossifying fibromas of the maxilla and mandible. Incisional
      biopsy revealed abundant spindle cells with areas of hemorrhage and haphazardly
      arranged diffuse multinucleated giant cells. DIAGNOSES: The patient was diagnosed
      with primary hyperparathyroidism (HPT). INTERVENTIONS: She was treated by
      parathyroidectomy. OUTCOMES: The multiple osteitis fibrosa cystica gradually
      resolved as bone re-mineralized. The patient has been followed up for 2 years
      without evidence of tumor recurrence. LESSONS: As multiple osteolytic lesions of
      facial bones can be caused by primary HPT, serum calcium and parathyroid hormone
      assays should be performed routinely when investigating these lesions.

PMID- 30113485
TI  - Late onset adrenal insufficiency after adrenalectomy due to latent nonclassical
      21-hydroxylase deficiency: A case report.
AB  - RATIONALE: Adrenal incidentaloma is sometimes complicated with 21-hydroxylase
      deficiency (21-OHD). Latent nonclassical 21-OHD in incidentaloma is difficult to
      diagnose. Although adrenalectomy in 21-OHD has been conducted when malignancy
      could not be excluded, adrenal insufficiency sometimes occurs, and it might not
      be observed immediately after operation. Here, we report a case of a 71-year-old
      man who experienced adrenal insufficiency over 2 decades postadrenalectomy,
      leading to a diagnosis of latent nonclassical 21-OHD. PATIENT CONCERNS: A 71-year
      old man was admitted to the hospital due to difficulty in movements and a sodium
      level of 119 mEq/L. His medical history revealed precocious puberty and left
      adrenalectomy because of an incidentaloma at 49 years of age, diagnosed
      pathologically as an adenoma. He did not attend follow-up visits because he did
      not have any symptoms. In 2017, 3 months before hospitalization, he experienced
      general fatigue. A few days before admittance, he complained of difficulty in
      moving and visual hallucination of small animals. DIAGNOSES: Laboratory
      evaluations revealed a high level of adrenocorticotropic hormone (ACTH) and low
      cortisol level. ACTH-stimulating test revealed a low basal level and low response
      for cortisol, and a high basal level and low response for 17-hydroxyprogesterone.
      We analyzed large gene deletion or conversion and the 9 most common micro
      mutations in the CYP21A2 gene by polymerase chain reaction; micro mutation of
      I172N and heterozygous large gene deletion or conversion were detected leading to
      the diagnosis of nonclassical 21-OHD. INTERVENTIONS: Immediately, 100 mg
      hydrocortisone was administered, followed by daily hydrocortisone and saline. The
      symptoms and hyponatremia improved in a few days. He was discharged from the
      hospital on day 34 with a daily dose of 15 mg hydrocortisone. LESSONS: Clinicians
      should be aware of late onset of adrenal insufficiency after adrenalectomy. In
      such cases, clinicians should not overlook the latent nonclassical 21-OHD.

PMID- 30113486
TI  - Novel surgical treatment of abdominal aortic aneurysm complicated with primary
      aorto-colonic fistula: A case report.
AB  - RATIONALE: Primary aorto-colonic fistula is a rare complication of an abdominal
      aortic aneurysm. Without surgical treatment, the associated mortality rate is
      100%. Even if patients receive timely surgical treatment, they may still die of
      complications such as infection. PATIENT CONCERNS: A 65-year-old male patient was
      transferred to our hospital because of massive hematochezia and abdominal pain.
      DIAGNOSES: Aortic computed tomography angiography demonstrated abdominal aortic
      aneurysm complicated with aorto-enteric fistula. INTERVENTIONS: We used a gelatin
      impregnated knitted vascular prosthesis to re-establish the aneurysm in its
      original position combined with local drainage to treat the fistula. OUTCOMES:
      The patient had an uneventful postoperative course, and there was no recurrence
      during the 18-month follow-up. LESSONS: This surgical treatment is suitable for
      patients with abdominal aortic aneurysms complicated with primary aorto-colonic
      fistula in which the intestine is very difficult to repair or resect.

PMID- 30113488
TI  - Aortic stenosis complicated by cardiogenic shock treated by transcatheter aortic
      valve replacement with extracorporeal membrane oxygenation: A case report.
AB  - RATIONALE: Cardiogenic shock secondary to aortic stenosis (AS) is a challenging
      problem owing to the high mortality associated with treatment, and successful
      treatment of such patients has been rare. PATIENT CONCERNS: A 77-year-old man
      presented with exercise intolerance and progressive exertional dyspnea and chest
      pain. The patient was suffered from cardiogenic shock after percutaneous coronary
      intervention. DIAGNOSIS: He was diagnosed by transthoracic echocardiography (TTE)
      and coronary angiogram. His main diagnose was AS and coronary artery disease.
      INTERVENTION: The patient received venoarterial extracorporeal membrane
      oxygenation (VA-ECMO) and transcatheter aortic valve replacement (TAVR). OUTCOME:
      As of the 5-month follow-up, the patient was well, and capable of basic
      independent living. The TTE suggested that the left ventricular end-diastolic
      volume had decreased from 66 to 45 mm and the left ventricular ejection fraction
      had risen from 20% to 50%. LESSONS: Patients with cardiogenic shock secondary to
      AS are very difficult to treat medically. ECMO with TAVR may be a reasonable
      strategy.

PMID- 30113487
TI  - Relationship of cardiac biomarkers with white matter hyperintensities in
      cardioembolic stroke due to atrial fibrillation and/or rheumatic heart disease.
AB  - White matter hyperintensities (WMHs), which are common in elderly people and
      contribute to age-related disability, can coexist with cardiac injury. It remains
      unclear whether cardiac biomarkers are associated with WMHs.To investigate this
      question, we prospectively recruited patients with cardioembolic stroke due to
      atrial fibrillation (AF) and/or rheumatic heart disease (RHD). Four cardiac
      biomarkers were measured: myoglobin, high-sensitivity cardiac troponin T (hs
      cTnT), creatine kinase-MB, and terminal pro-brain natriuretic peptide. WMHs in
      periventricular and deep white matter were assessed separately.In the entire
      sample of 171 patients, 120 (70.2%) presented with WMHs, of whom 18 (10.5%)
      presented with moderate to severe deep white matter hyperintensities (DWMH) and
      55 (32.2%) presented with moderate to severe periventricular hyperintensities
      (PVH). Risk of moderate to severe PVH, after adjusting for confounders, was 2.460
      fold higher in patients with high myoglobin levels than in those with low levels,
      and the risk was 2.608-fold higher in patients with high hs-cTnT levels than in
      those with low levels. There were no significant associations between any of the
      4 cardiac biomarkers and moderate to severe DWMH.This prospective observational
      study provides new evidence of the potential relationship of cardiac biomarkers
      with WMHs in patients with cardioembolic stroke due to AF and/or RHD. We found
      that elevated myoglobin levels and high hs-TnT levels were independently
      associated with the presence of moderate to severe PVH. Further studies are
      required to test our findings and explore whether cardiac biomarkers contribute
      directly to WMHs pathogenesis.

PMID- 30113489
TI  - Association between serum vitamin D deficiency and age-related macular
      degeneration in Koreans: Clinical case-control pilot study.
AB  - The objective of this study was to evaluate the association between serum vitamin
      D deficiency and age-related macular degeneration (AMD) in Koreans through a
      clinical case-control pilot study. The study included 96 patients: 30 with late
      AMD, 32 with early AMD, and 34 normal controls. The patients with late AMD were
      divided into 2 subgroups based on the presence or absence of subretinal fibrosis
      on optical coherence tomography (OCT) images. We measured 25-hydroxyvitamin D
      levels in the serum of all patients during the same season to rule out seasonal
      variation of serum vitamin D level. Serum vitamin D deficiency was defined as a
      serum 25-hydroxyvitamin D level below 20 ng/mL. Serum vitamin D deficiency had a
      tendency to increase the risk of early AMD, although with borderline significance
      [odds ratio (OR) = 3.59; 95% confidence interval (95% CI) 0.95-13.58; P = .060].
      It was significantly associated with a greater risk of late AMD (OR = 3.61; 95%CI
      1.04-12.51; P = .043). Among the 2 subgroups of patients with late AMD, those
      with subretinal fibrosis present on the OCT images showed a greater risk of serum
      vitamin D deficiency than the normal controls (OR = 7.54; 95% CI 1.34-42.51).
      However, there was no significant association between serum vitamin D deficiency
      and late AMD without subretinal fibrosis (OR = 1.89; 95% CI 0.40-8.92). Serum
      vitamin D deficiency may increase the risk of early and late AMD in Koreans, and
      may also be associated with subretinal fibrosis in this population.

PMID- 30113491
TI  - Surgical decompression of the lateral femoral cutaneous nerve (LFCN) for Meralgia
      paresthetica treatment: Experimental or state of the art? A single-center outcome
      analysis.
AB  - Meralgia paresthetica (MP) is a rare lateral femoral cutaneous nerve-(LFCN)
      mononeuropathy. Treatment for this disorder includes conservative and operative
      approaches; the latter is considered if conservative therapy fails. The most
      commonly used surgical approaches are decompression/neurolysis and
      avulsion/neurectomy. However, there are no definitive guidelines on the optimal
      surgical approach to be used. The purpose of this study was to evaluate the
      outcome of surgical decompression of the LFCN for the treatment of persistent MP
      with preservation of sensation along the distribution of the LFCN.We evaluated
      the outcomes of LFCN procedures performed between 2015 and 2016. A total of 16
      surgical decompressions could be identified. Retrospective analysis of
      prospectively collected patient data was performed, as well as systematic
      evaluation of the postoperative course, with regular follow-up examinations based
      on a standardized protocol. Pain was analyzed using an NRS (numeric rating
      scale). Several postsurgical parameters, including temperature hypersensitivity
      and numbness in the LFCN region, were compared with the presurgical data.Sixty
      nine percent of patients had histories of trauma or surgery, which were
      designated as the onset of pain. Of these patients, 78% had hip prostheses, 2 had
      previous falls. Postoperatively, a significant reduction of 6.6 points in the
      mean NRS pain value was observed. All other evaluated parameters also improved
      postoperatively. Patient satisfaction was high, with 86% reporting complete
      satisfaction, and 14% reporting partial satisfaction.Previous studies favor
      either avulsion/neurectomy as the preferred procedure for MP treatment, or
      provide no recommendation. Our findings instead confirm the
      decompression/neurolysis approach as the primary surgical procedure of choice for
      the treatment of MP, if conservative treatment fails.

PMID- 30113490
TI  - Performance of 5 disseminated intravascular coagulation score systems in
      predicting mortality in patients with severe trauma.
AB  - The present study aimed to analyze and compare the prognostic performances of the
      Japanese Ministry of Health and Welfare (JMHW) score, the Korean Society on
      Thrombosis and Hemostasis (KSTH) score, the International Society on Thrombosis
      and Haemostasis (ISTH) score, the Japanese Association for Acute Medicine (JAAM)
      score, and the revised JAAM (rJAAM) score, for 28-day mortality in severe
      trauma.This retrospective observational study included patients admitted for
      severe trauma between 2012 and 2015. Receiver operating characteristics analysis
      was performed to examine the prognostic performance of the 5 different DIC score
      systems. The primary outcome was 28-day mortality following an injury.Of the 1266
      patients included in the study, 28-day mortality rate was 19.7% (n = 249). The
      area under the curves (AUCs) of JMHW, KSTH, ISTH, JAAM, and rJAAM scores for 28
      day mortality were 0.751 [95% confidence interval (95% CI), 0.726-0.775], 0.726
      (95% CI, 0.701-0.750), 0.700 (95% CI, 0.674-0.725), 0.673 (95% CI, 0.646-0.699),
      and 0.676 (95% CI, 0.649-0.701), respectively. The AUC of JMHW score was
      significantly different from those of the other score systems. Fibrinogen levels
      <=1.0 g/L [odds ratio (OR), 1.824; 95% CI, 1.029-3.232] and 1.0 to 1.5 g/L (OR,
      1.697; 95% CI, 1.058-2.724) were independently associated with 28-day mortality
      compared with fibrinogen level above 1.5 g/L.JMHW score has the highest
      prognostic performance for 28-day mortality among DIC score systems in severe
      trauma. Fibrinogen level seemed to have a role in greater discrimination of JMHW
      scores than the other DIC score systems.

PMID- 30113492
TI  - Antilung cancer effect of ergosterol and cisplatin-loaded liposomes modified with
      cyclic arginine-glycine-aspartic acid and octa-arginine peptides.
AB  - BACKGROUND: Lung cancer is one of the most important diseases threatening human
      health, and targeted therapy has become the main research direction. This work,
      therefore, aimed to develop cyclic arginine-glycine-aspartic (RGD) and octa
      arginine (R8) peptide-modified ergosterol (ERG)-combined cisplatin
      (diamminedichloridoplatinum(II) [DDP]) liposomes (LIP) as a drug delivery system.
      METHODS: Soybean phospholipids (SPC) and cholesterol (Chol) were selected to
      prepare different LIPs: ERG-loaded LIP (ERG-LIP), DDP and ERG-LIP (DDP/ERG-LIP),
      R8 peptide-modified DDP and ERG-LIP (R8-DDP/ERG-LIP), and cyclic RGD and R8
      DDP/ERG-LIP (RGD/R8-DDP/ERG-LIP). The quality, tumor sphere penetrating ability,
      in vitro cellular uptake, mechanism of cellular uptake, and in vitro cytotoxicity
      of RGD/R8-DDP/ERG-LIP were evaluated. RESULTS: The LIP quality evaluation
      revealed that RGD/R8-DDP/ERG-LIP is round with a double-layer structure. The
      average particle size, dispersion coefficient of the polydispersity index (PDI),
      and zeta potential of RGD/R8-DDP/ERG-LIP were 155.2 +/- 8.7 nm, 0.102, and 4.74
      +/- 0.7 mV, respectively. Furthermore, the LIPs were stable in the serum, and
      obviously inhibited the growth of A549 lung cancer cells with RGD/R8-DDP/ERG-LIP
      exhibiting the strongest inhibitory effect. The highest cellular uptake rate,
      which was at 4 hours, was exhibited by RGD/R8-DDP/ERG-LIP in a concentration
      dependent manner. CONCLUSION: The results showed that LIP uptake by A549 cells
      was mainly by the clathrin-mediated endocytosis pathway (chlorpromazine). The
      results also suggest that RGD/R8-DDP/ERG-LIP might be a promising drug delivery
      system to improve antilung cancer drug effect and tumor-targeting in vitro.

PMID- 30113493
TI  - Clinicopathological study of 9 cases of megakaryocytes in pleural and peritoneal
      fluids.
AB  - To systemically analyze megakaryocytes in pleural and peritoneal fluids and their
      clinical significance. We retrospectively examined 10,846 pleural, peritoneal,
      and pericardial fluid samples obtained from 3 hospitals over a 20-year period.
      Megakaryocytes were observed in the pleural fluid samples from 7 patients and
      peritoneal fluid samples from 2 patients, and the incidence was 0.83%. The
      clinical diagnoses of these 9 patients included myeloproliferative disorders,
      trauma, and tumors. The serous effusions in all 9 patients were bloody, and the
      megakaryocytes could be associated with trauma, bone marrow pollution,
      extramedullary hematopoiesis, or cancer. Additionally, differentiating between
      megakaryocytes and tumor cells or nuclear mesothelial cells in the pleural fluid
      is difficult. Therefore, megakaryocytes should be carefully observed and
      differentiated in pleural and peritoneal fluids because they can be confused with
      other cells in the clinic. Altogether, the megakaryocytes in the pleural and
      peritoneal fluids were mainly associated with contamination in the bone marrow or
      extramedullary hematopoiesis.

PMID- 30113494
TI  - Surgical approach towards Grynfelt hernia: A single center experience.
AB  - Due to the rarity of Grynfelt hernia, there is no standardized surgical
      technique.From April 2010 to September 2017, 12 cases of primary superior lumbar
      hernia (Grynfelt hernia) were identified through medical records reviewing and
      included in our study. Perioperative data, surgical outcomes, and long-term
      follow-up results were retrospectively analysed.Male/female ratio of patients was
      1:1, with age 69.5 (62, 74.5) [median (25 percentile, 75 percentile)] years old.
      Right/left side ratio of lumbar hernia was 9/3. The in-hospital duration was 7
      (5, 8) days. The surgical duration was 35 (30, 50) minutes. The defect size was
      2.1 (1.5, 3) cm in diameter. The discharge of the patient was on 3 (2, 4) post
      operative day (POD). The meshes used were: MK5816 (10), MK5810 (1), and UHS (1).
      There was only 1 case of postoperative complication where the patient was
      admitted in intensive care unit (ICU) due to hypoxemia. Morbidity, mortality, and
      recurrence cases were null.Our study indicates that open surgery with mesh
      implantation is a reliable way for the management of primary superior lumbar
      hernia.

PMID- 30113495
TI  - Role of C-reactive protein and procalcitonin in discriminating between infectious
      fever and tumor fever in non-neutropenic lung cancer patients.
AB  - This study assessed whether C-reactive protein (CRP) and procalcitonin (PCT)
      levels can discriminate between infectious fever and tumor fever (TF) in non
      neutropenic patients with nonsmall cell lung cancer (NSCLC).This retrospective
      clinical study included 96 adults with NSCLC who were admitted to the Third
      Hospital of Hebei Medical University between July 2015 and July 2017. Febrile,
      non-neutropenic patients were enrolled. CRP and PCT levels, neutrophil count, and
      antimicrobial response were evaluated.This study included 26 patients with TF, 49
      with localized bacterial infection (LBI), and 21 with bloodstream infection
      (BSI). CRP levels in BSI were significantly higher than in TF (P < .05) and LBI
      (P < .05). No statistically significant difference was found between patients
      with TF and LBI (P > .05). PCT levels were significantly higher in BSI and LBI
      than in TF (P < .05). CRP and PCT levels in patients with stage IV disease were
      significantly higher than in those with stage II to III disease (P < .05). CRP
      and PCT levels declined significantly in patients with BSI who were responding to
      antimicrobials (P < .05).Compared with CRP levels, PCT levels can discriminate
      between TF and infectious fever more accurately. PCT and CRP levels may predict
      different stages of lung cancer.

PMID- 30113496
TI  - Lower risk of musculoskeletal pain among patients with end-stage renal disease
      treated by hemodialysis: A frequency-matched retrospective cohort study.
AB  - Musculoskeletal pain is experienced by 5%-14% of the general adult population,
      and it is highly common among patients with chronic kidney disease (CKD).
      Therefore, the purpose of the study was to decide the prevalent rate of
      musculoskeletal pain in end-stage renal disease (ESRD) patients and to analyze
      this relationship between myalgia and ESRD using clinical features and
      determinants.A total of 93,013 patients who received ESRD diagnoses during 2000
      and 2010 and were followed up until December 31, 2011, were identified from the
      Longitudinal Health Insurance Database 2000 (LHID2000) of the National Health
      Research Institutes (NHRI); non-ESRD controls were also selected from the
      LHID2000.The results indicated that the risk of chronic musculoskeletal pain is
      significantly lower in the hemodialysis treated ESRD cohort (subhazard ratio =
      0.52, P < .0001), despite of sex, age, or comorbidities. Older patients were
      discovered to be at lower risk of chronic musculoskeletal pain (subhazard ratio =
      0.94, P = .0765), with those aged 40 to 64 years having the highest hazard ratios
      (subhazard ratio = 1.21, P < .0001), and the prevalence of chronic
      musculoskeletal pain in women was higher than that in men (vs female sex;
      subhazard ratio = 0.69, P < .0001). Kaplan-Meier analysis revealed a higher
      cumulative incidence of myalgia development in the non-ESRD cohort compared with
      the ESRD cohort (log-rank test, P < .001).Clinicians should assess the risk of
      chronic musculoskeletal pain in such patients and provide appropriate and timely
      support of hemodialysis.

PMID- 30113497
TI  - Comparative analysis of immune checkpoint inhibitors and chemotherapy in the
      treatment of advanced non-small cell lung cancer: A meta-analysis of randomized
      controlled trials.
AB  - BACKGROUND: Recently, immune checkpoint inhibitors have shown survival advantage
      over chemotherapy in the treatment of advanced non-small cell lung cancer
      (NSCLC). This meta-analysis was conducted to gather and analyze the available
      evidence (Evidence level I; Randomized Controlled Trials) comparing efficacy and
      safety of anti-programmed cell death-1 (PD1)/programmed cell death ligand 1 (PD
      L1) therapies and chemotherapy in the treatment of advanced NSCLC. METHODS: A
      search strategy was devised to identify the randomized controlled trials (RCTs)
      using electronic databases of PubMed, Cochrane Library, and Web of Science.
      Hazard ratios or odds ratios obtained for overall survival (OS), progression-free
      survival (PFS), objective response rate (ORR), and treatment related adverse
      events (TRAEs) were analyzed using fixed effect model or random effects model.
      Additionally, subgroup analysis was also performed. RESULTS: A total of seven
      RCTs (n = 3867) were identified and selected for inclusion in this meta-analysis.
      Anti-PD1/PD-L1 therapies (nivolumab, pembrolizumab, atezolizumab) resulted in
      better OS (HR 0.72 [95% confidence interval [CI] 0.63, 0.82; P < .00001]), PFS
      (HR 0.84 [95% CI 0.72, 0.97; P < .02]), and ORR (odds ratio [OR] 1.52 [95% CI
      1.08, 2.14; P < .02]) in comparison to chemotherapy in advanced NSCLC. Improved
      safety was observed with anti-PD1/PD-L1 therapies (OR 0.31 [95%CI 0.26, 0.38; P <
      .00001]). Subgroups analysis revealed Eastern Cooperative Oncology Group
      Performance Status (ECOG PS) 1 (HR 0.76 [95%CI 0.62, 0.93; P = .007]), squamous
      cell type (HR 0.76 [95% CI 0.63, 0.92; P = .005]), current/former smoker (HR 0.76
      [95% CI 0.63, 0.92; P = .005]), epidermal growth factor receptor (EGFR) wild type
      (HR 0.67 [95% CI 0.60, 0.76; P < .00001]), Kirsten rat sarcoma oncogene mutation
      (KRAS) mutant (HR 0.60 [95% CI 0.39, 0.93; P < .02]), and absence of central
      nervous system (CNS) metastases (HR 0.71 [95% CI 0.63, 0.80; P < .00001]) were
      associated with better overall survival. CONCLUSIONS: Anti-PD1/PD-L1 therapies
      are safe and effective treatment option in advanced non-small cell lung cancer
      and can be recommended selectively.

PMID- 30113498
TI  - Hybrid coronary revascularization versus conventional coronary artery bypass
      grafting: Systematic review and meta-analysis.
AB  - BACKGROUND: Hybrid coronary revascularization (HCR) combining minimally invasive
      grafting of the left internal mammary artery to the left anterior descending
      artery with percutaneous coronary intervention has become a viable option for
      treating coronary artery disease. The aim of this meta-analysis was to compare
      HCR with conventional coronary artery bypass grafting (CABG) in a range of
      clinical outcomes and hospital costs. METHODS: To identify potential studies,
      systematic searches were carried out in various databases. The key search terms
      included "hybrid revascularization" AND "coronary artery bypass grafting" OR
      "HCR" OR "CABG." This was followed by a meta-analysis investigating the need for
      blood transfusion, hospital costs, ventilation time, hospital stay,
      cerebrovascular accident, myocardial infarction, mortality, postoperative atrial
      fibrillation, renal failure, operation duration, and ICU stay. RESULTS: The
      requirement for blood transfusion was significantly lower for HCR: odds ratio
      0.38 (95% confidence intervals [CIs] 0.31-0.46, P < .00001) as was the hospital
      stay: mean difference (MD) -1.48 days (95% CI, -2.61 to -0.36, P = 0.01) and the
      ventilation time: MD -8.99 hours (95% CI, -15.85 to -2.13, P = .01). On the
      contrary, hospital costs were more expensive for HCR: MD $3970 (95% CI, 2570
      5370, P < .00001). All other comparisons were insignificant. CONCLUSIONS: In the
      short-term, HCR is as safe as conventional CABG and may offer certain benefits
      such as a lower requirement for blood transfusion and shorter hospital stays.
      However, HCR is more expensive than conventional CABG.

PMID- 30113499
TI  - Comparative effectiveness of hyperthermic intraperitoneal chemotherapy for
      gastric cancer: A systematic review and network meta-analysis protocol.
AB  - BACKGROUND: Comparative efficacy and safety of different hyperthermic
      intraperitoneal chemotherapies (HIPEC) in patients with advanced gastric cancer
      who underwent gastrectomy is unclear. To investigate this question, we conduct a
      systematic review and network meta-analysis. METHODS: The protocol followed
      Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols.
      PubMed, Embase, and the Cochrane Library will be searched systematically for
      eligible randomized controlled trials without language restriction. The primary
      outcome is overall survival. The second outcomes are postoperative complications.
      The surface under the cumulative ranking curve value will be calculated to
      establish a hierarchy of the treatments. RESULTS: The results will provide useful
      information about the effectiveness and safety of HIPEC regimens in patients with
      resected gastric cancer. CONCLUSION: The findings of the study will be
      disseminated through peer-reviewed journal.

PMID- 30113501
TI  - A new percutaneous method for inframammary fold reconstruction in implant-based
      breast reconstruction: Vertical pendulum suture.
AB  - Several operative techniques for inframammary fold (IMF) reconstruction have been
      described and have resolved the shortcomings of conventional methods. However,
      there are still difficulties with IMF reconstruction, that is, performance
      through small mastectomy scars, creation of a smooth IMF curve, transfer of
      external IMF markings to the interior chest wall, or determining correct IMF
      without an implant in place. We have used a type of anchor suture with a
      completely percutaneous approach, the vertical pendulum suture (VP suture), to
      reconstruct the IMF easily in implant-based breast reconstruction.The VP suture
      requires a pair of skin incisions a few millimeters in length (incisions A and
      B). The needle passes through the subcutaneous tissue from incision A, the chest
      wall, again through the subcutaneous tissue, and exits from incision B. Then, the
      needle passes through the edge of the dermis from incision B, the superficial
      layer of the subcutaneous tissue, again through the other edge of the dermis, and
      exits from incision A. The knot is tied and buried in the subcutaneous tissue.
      The whole technique can be performed percutaneously without visualizing the
      inside of the pocket. A retrospective case series study of photographs and chart
      review was conducted for all cases of unilateral implant-based breast
      reconstruction performed from December 2016 to December 2017 at Ina Central
      Hospital, Ina, Japan.Nine consecutive patients underwent unilateral implant-based
      breast reconstruction. Five patients treated using the VP suture were included in
      this study. All 5 patients showed good esthetic results over the follow-up period
      (average, 11 months). Scalloped appearance was observed in all patients, but
      flattened spontaneously and disappeared within 3 months postoperatively. There
      were no complications, such as hematoma, infection, skin necrosis, pneumothorax,
      seroma, scar contracture, or implant injury.The VP suture is completely
      percutaneous, parallel to the IMF, and is easy to perform at any time during
      surgery regardless of whether the implant is in place or not. IMF reconstruction
      is facilitated by freeing the surgeon from the need to visualize the inside of
      the pocket.

PMID- 30113500
TI  - Detection of spleen, kidney and liver infarcts by abdominal computed tomography
      does not affect the outcome in patients with left-side infective endocarditis.
AB  - Extra-cardiac abdominal complications are common in left-side infective
      endocarditis (LS-IE). The aim of this work was to study whether patients with LS
      IE presenting splenic, renal, or liver (SRL) involvement seen in abdominal
      computed tomography (CT) had different clinical features, therapeutic plans, and
      outcome than those without these findings on CT.From January 2008 to April 2010,
      multidisciplinary teams have prospectively collected all consecutive cases of IE,
      diagnosed according to the Duke criteria, in which abdominal CT was performed.A
      total of 147 patients with LS-IE had abdominal CT. Fifty (34%) had SRL lesions:
      46 splenic, 15 renal, 1 liver infarct, and 2 liver abscesses. Patients with SRL
      lesions were mainly men (P = .01), had liver disease (P = .001) with natural
      valve (P = .050) and mitro-aortic valve involvement (P = .042), splenomegaly (P =
      .001), nonabdominal emboli (P = .001), and a greater number and larger vegetation
      (>15 mm, P = .049) in the mitro-aortic valves (P = .051) than patients with
      normal abdominal CT. The site of acquisition, clinical characteristics,
      microbiology, surgical treatment, days of hospitalization, hospital death, and 1
      year mortality were similar in patients with and without SRL emboli on CT. In the
      stepwise logistic regression analysis, male gender (odds ratio [OR] = 3.6, 95%
      confidence interval [CI] = 1.4-9.1), liver disease (OR = 8.3, 95% CI = 2.1-31.8),
      and nonabdominal emboli (OR = 5.2, 95% CI = 2.3-11.7) were independently
      associated with SRL lesions.Male patients with native LS-IE who had liver disease
      and nonabdominal emboli had more frequent abdominal lesions seen on CT. The
      presence of SRL infarcts on abdominal CT scan performed on patients with LS-IE
      seems to have poor practical implications, and as a consequence, its realization
      should only be considered when there are symptoms or signs that suggest them.

PMID- 30113504
TI  - Characteristics, outcome and treatments with cranial pachymeningitis: A
      multicenter French retrospective study of 60 patients: Erratum.

PMID- 30113502
TI  - Unilateral versus bilateral percutaneous balloon kyphoplasty for osteoporotic
      vertebral compression fractures: A systematic review of overlapping meta
      analyses.
AB  - BACKGROUND: Unilateral and bilateral percutaneous balloon kyphoplasty (PKP) are 2
      main approaches for the treatment of patients with osteoporotic vertebral
      compression fractures (OVCFs). Numerous published systematic reviews and meta
      analyses evaluating the effectiveness of 2 approaches remain inconclusive. In
      order to propose a significant principle to make decisions for comparing clinical
      safety and efficacy of unilateral versus bilateral PKP for treating OVCFs
      patients based on the currently best available evidence, a systematic review of
      overlapping meta-analysis was conducted. METHODS: Three electronic databases,
      Pubmed/Medline, Embase2 and the Cochrance Library, were searched systematically
      to retrieve and identify all eligible systematic reviews and meta-analyses
      comparing unilateral and bilateral PKP for the treatment of patients with OVCFs.
      Only systematic reviews or meta-analyses with an exclusively pooled analysis of
      randomized controlled trials (RCTs) met the minimum eligibility criteria in this
      investigation. The Oxford Levels of Evidence, Jadad algorithm and Assessment of
      Multiple Systematic Reviews (AMSTAR) instrument were adopted for evaluation of
      the methodological quality for each included literature to select currently best
      available evidence. RESULTS: Screening determined that out of 2159, 9 meta
      analyses with level II or III of evidence met the inclusion criteria in the
      systematic review of overlapping meta-analyses. The multiple systematic reviews
      scores ranged from 8 to 9 with a mean of 8.55 (median 8.5). According to the
      search process and selection strategies of the Jadad algorithm, a meta-analysis
      by Feng et al with the best available evidence (12 RCTs and an AMSTAR score of 9)
      demonstrated that unilateral and bilateral PKP are both nice choices for the
      treatment of patients with OVCFs, and no significant differences were revealed in
      clinical scores, radiological outcomes, and quality of life with long-term follow
      up. However, compared with bilateral PKP, unilateral PKP produced a shorter
      surgery time, smaller dosage of cement, lower risk of cement leakage, and
      relieved a higher degree of intractable pain at short-term follow-up after
      surgery. CONCLUSION: Unilateral percutaneous balloon kyphoplasty is more
      advantageous and superior to bilateral percutaneous kyphoplasty, and should be
      considered an effective option for the treatment of patients with osteoporotic
      vertebral compression fractures.

PMID- 30113505
TI  - Eunkyosan for treatment of the common cold: A protocol for the systematic review
      of controlled trials: Erratum.

PMID- 30113506
TI  - Parecoxib prevents early postoperative cognitive dysfunction in elderly patients
      undergoing total knee arthroplasty: A double-blind, randomized clinical consort
      study: Erratum.

PMID- 30113503
TI  - The value of 3-dimensional color Doppler in predicting intraoperative hemorrhage
      for cesarean scar pregnancy.
AB  - The aim of this study is to evaluate the efficacy of 3-dimensional (3D)
      ultrasonography and 3D color power Doppler ultrasound in the management of
      cesarean scar pregnancy (CSP).A case-control study enrolled 190 CSP patients who
      underwent uterine artery embolization (UAE) in combination with dilatation and
      curettage (D&C). The maximum diameter of gestational sac or CSP mass, uterine
      scar thickness, and resistance index (RI) were measured by 2D ultrasound. The
      lesion volume, vascular index (VI), flow index (FI), blood vessels, and blood
      flow index (VFI) were assessed by 3D ultrasound. The changes of these parameters
      before and after UAE were analyzed. Then, the patients were divided into bleeding
      group and control group according to the intraoperative hemorrhage during D&C to
      access and compare the significance of 2D and 3D parameters in intraoperative
      hemorrhage.The mean VI and the mean VFI were significantly reduced after
      embolization (P < .01). In the bleeding group, the lesion volume and diameter of
      gestational sac or CSP mass were significantly larger, VI and VFI were
      significantly higher, the uterine scar thickness was thinner, and RI was lower (P
      < .05). The best indicator for prediction of massive intraoperative bleeding was
      the VI with an area under the curve of 0.870, the best cut-off value of VI was
      7.500, and the sensitivity and specificity were 88.2% and 82.4%, respectively. In
      comparing the receiver operating characteristic curves among 2D and 3D ultrasound
      parameters, the diagnostic efficacy of lesion volume was significantly higher
      than maximum diameter (P < .001). The diagnostic efficacy of VI was significantly
      higher than maximum diameter (P = .020) and RI (P = .011).UAE reduces the number
      of vessels and the blood flow perfusion obviously; however, it does not reduce
      lesion size or increases myometrial thickness. Three-dimensional ultrasonography
      and power Doppler, especially VI, lesion volume may be helpful in predicting
      excessive bleeding during D&C after UAE.

PMID- 30113507
TI  - A multicenter, open-label, phase III study of Abcertin in Gaucher disease:
      Erratum.

PMID- 30113508
TI  - CO2 Laser-assisted Deep Sclerectomy Combined With Phacoemulsification in Patients
      With Primary Open-angle Glaucoma and Cataract.
AB  - PURPOSE: To assess the safety and efficacy of CO2 laser-assisted sclerectomy
      surgery (CLASS) combined with phacoemulsification in patients with primary open
      angle glaucoma (POAG) and visually significant cataracts. MATERIALS AND METHODS:
      This was a prospective, uncontrolled, interventional case series. Seventeen
      patients (17 eyes) diagnosed with POAG and cataracts were enrolled starting from
      November 2015. All subjects underwent CLASS combined with phacoemulsification
      surgery by the same surgeon. After the surgery, all patients were followed for 12
      months. The preoperative to postoperative changes in intraocular pressure (IOP),
      glaucoma medication requirements, best-corrected visual acuity and adverse events
      were recorded. RESULTS: The results of 17 eyes of 17 patients were included in
      the statistical analysis. The baseline mean IOP was 23.94+/-8.57 mm Hg (mean+/
      SD), and patients used 2.18+/-0.88 types of antiglaucoma medication. At 12 months
      postsurgery, the mean IOP was 14.67+/-2.97 mm Hg, and patients used 0.59+/-0.87
      types of antiglaucoma medication (both P<0.001). The logarithm of the minimal
      angle of resolution of the best-corrected visual acuity improved from 0.77+/-0.42
      preoperatively to 0.33+/-0.47 postoperatively (P<0.05). Two patients experienced
      intraoperative perforation accompanied by iris prolapse. One patient exhibited
      postoperative choroidal detachment. CONCLUSIONS: CLASS with phacoemulsification
      may become a safe and effective intervention for patients with POAG and visually
      significant cataracts.

PMID- 30113509
TI  - Safety and Efficacy of Diode Laser Transscleral Cyclophotocoagulation in Eyes
      With Good Visual Acuity.
AB  - BACKGROUND/AIMS: The main aim of this study was to evaluate the safety and
      efficacy of diode laser transscleral cyclophotocoagulation (TSCPC) in eyes with
      good visual acuity. PATIENTS AND METHODS: A retrospective chart review identified
      patients who underwent TSCPC for uncontrolled intraocular pressure (IOP) from
      2014 to 2016. Enrollment criteria included pretreatment best-corrected visual
      acuity (BCVA) of 20 of 40 or better, and a minimum of 6 months of postoperative
      follow-up. RESULTS: Thirty-three eyes of 33 patients(mean age, 72.1+/-16.0 y)
      were enrolled (mean follow-up 12.6+/-6.1 mo). The mean (SD) IOP was reduced 48.3%
      from 27.1 mm Hg (7.8) at baseline to 13.1 mm Hg (4.2) at last follow-up.
      Reduction of >=1 glaucoma medications was achieved in 17 eyes (51.5%) at last
      follow-up. The cumulative probability of complete success (BCVA loss <2 Snelling
      lines, 20% reduction IOP, no reoperation for glaucoma, no IOP<5 mm Hg) was 78.8%
      and 50% at months 6 and 12, respectively. The cumulative probability of qualified
      success (BCVA>=2 lines with >=20% reduction IOP, no reoperation for glaucoma, no
      IOP<5 mm Hg) was 90.1% and 81.3% at month 6 and 1 year, respectively. Significant
      vision loss, defined as BCVA>=2 lines, occurred in 33% of patients. The most
      common complications were postoperative iritic (56.3%) and cystoid macular edema
      (12.5%). CONCLUSIONS: TSCPC demonstrates a strong reduction in IOP and glaucoma
      medication use. However, with significant vision loss in 33% of patients, future
      prospective studies with a comparison group receiving traditional glaucoma
      surgery are needed to determine comparative safety and efficacy.

PMID- 30113510
TI  - Extrusion and Breakage of XEN Gel Stent Resulting in Endophthalmitis.
AB  - The mainstay of open-angle glaucoma surgery involves subconjunctival drainage of
      aqueous fluid. Insertion of the XEN Gel Stent leads to formation of a
      subconjunctival bleb to assist in the drainage of aqueous fluid and offers the
      advantage of ease and speed of insertion with conjunctival sparing over
      traditional surgical techniques. This is the first case of XEN Gel Stent-related
      endophthalmitis associated with extrusion and breakage of the stent, a previously
      undocumented complication of this relatively new surgery.

PMID- 30113511
TI  - Needling With 5-Fluorouracil (5-FU) After XEN Gel Stent Implantation: 6-Month
      Outcomes.
AB  - PURPOSE: The purpose of this study was to evaluate frequency, safety, and
      efficacy of needling in patients that underwent XEN Gel Stent implantation.
      METHODS: Retrospective case review of 19 eyes of 57 consecutive patients (61
      eyes) with primary open-angle glaucoma or pseudoexfoliative glaucoma that
      previously underwent implantation of XEN45 alone or in combination with cataract
      surgery followed by needling procedure with 5-FU. Success was defined at 2 IOP
      levels: <=21 mm Hg and <=15 mm Hg, with or without additional glaucoma
      medications. Treatment failure was defined as IOP>21 mm Hg or <5 mm Hg, need for
      additional glaucoma surgery or loss of light perception. RESULTS: Totally 19 of
      61 eyes that underwent XEN gel implantation had subsequent needling and were
      included. Preneedling IOP was 26.2+/-9.5 and postneedling IOP at last follow-up
      15.4+/-3.7 mm Hg (P=0.0001). Overall success rates of 17 (90%) and 13 eyes (69%)
      were observed at the <=21 mm Hg and <=15 mm Hg level, respectively. Preneedling
      and postneedling visual acuity and number of medications remained unchanged
      (P>0.05). Two eyes (10%) were categorized as treatment failures. No major
      complications occurred. Mean follow-up was 203.8+/-142.2 (range, 22 to 456) days.
      CONCLUSIONS: Needling revision following XEN gel stent implantation showed a good
      IOP-lowering effect without significant increase in number of antiglaucoma
      medications, decrease in visual acuity, nor any major complications. Further
      studies with long-term follow-up and a larger number of patients are needed to
      fully assess the safety and efficacy of this procedure.

PMID- 30113512
TI  - Predictors of Outcome in Selective Laser Trabeculoplasty: A Long-term Observation
      Study in Primary Angle-closure Glaucoma After Laser Peripheral Iridotomy Compared
      With Primary Open-angle Glaucoma.
AB  - PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) for
      patients with primary angle-closure glaucoma (PACG) following a YAG laser
      peripheral iridotomy (PI) in comparison with primary open-angle glaucoma (POAG)
      and to assess the predictors of outcome of SLT. PATIENTS AND METHODS: In
      retrospective study 68 patients with PACG after PI (68 eyes) and 74 POAG patients
      (74 eyes) were observed for 6 years. The effectiveness of SLT (20% reduction of
      intraocular pressure) was assessed using Kaplan-Meier survival analysis. The
      parameters for distinguishing the eyes with success and failure of SLT were
      detected by means of area under receiver operating characteristic curve (AUC).
      The predictive factors affecting SLT outcome were determined using Cox-regression
      analysis. RESULTS: The success ratio was 87% in both groups in 1 year and dropped
      to 4% in PACG and to 6% in POAG in 6 years. Corneal hysteresis [odds ratio
      (OR)=0.367, R=0.005 for PACG, OR=0.446, R=0.008 for POAG] and age (OR=1.182,
      P=0.012 for PACG, OR=1.164, P=0.002 for POAG) were detected as the predictors of
      SLT outcome. In PACG pre-SLT anterior chamber depth was additional predictor
      (OR=0.242, R=0.001). The number of pre-SLT pressure-lowing medications was higher
      in the eyes with SLT failure (AUC, 0.794; P=0.0005 in PACG and AUC, 0.760;
      P=0.014 in POAG). CONCLUSIONS: One-year efficacy of SLT in POAG and PACG after PI
      was high, but it was reduced in long-term period. Corneal hysteresis, age, and
      number of pre-SLT hypotensive eye drops were significant prognostic factors for
      treatment success in both glaucoma forms. In PACG pre-SLT anterior chamber depth
      affected the SLT outcome.

PMID- 30113513
TI  - Effects of Circumpapillary Retinal Nerve Fiber Layer Segmentation Error
      Correction on Glaucoma Diagnosis in Myopic Eyes.
AB  - PURPOSE: In a myopic population, we investigated the occurrence of
      circumpapillary retinal nerve fiber layer (RNFL) segmentation errors that
      required manual correction in optical coherence tomography (OCT) and its effect
      on glaucoma diagnostic capability of OCT. MATERIALS AND METHODS: Myopic subjects
      (spherical equivalent refractive error <-3 D) with and without primary open-angle
      glaucoma were recruited. Three circumpapillary RNFL scans with diameters of 3.45,
      4.50, and 6.00 mm were obtained using spectral-domain OCT. RNFL segmentation
      errors were manually corrected. Receiver operating characteristic curves of
      retinal nerve fiber layer thickness (RNFLT) were obtained and area under the
      curves were calculated before and after manual correction. RESULTS: In total, 90
      myopic eyes with glaucoma (90 patients; visual field mean deviation, -9.5+/-7.1
      dB) and 58 myopic eyes without glaucoma (58 control subjects) were included.
      Glaucomatous eyes required manual correction more frequently than control eyes
      (56% vs. 32% of RNFL OCT scans; P<0.001). After manual correction in the glaucoma
      group, the global RNFLT decreased significantly from 61.8 to 57.5 um (P=0.025),
      50.8 to 47.2 um (P=0.019), and 45.5 to 39.6 um (P=0.006) for the 3.45-, 4.50-,
      and 6.00-mm scans, respectively. After manual correction of RNFL segmentation
      errors, the glaucoma diagnostic capability of the global RNFLT improved
      significantly; the area under the curves increased from 0.827 to 0.886 (P=0.017),
      0.829 to 0.880 (P=0.033), and 0.762 to 0.846 (P=0.006) for the 3.45-, 4.50-, and
      6.00-mm scans, respectively. CONCLUSIONS: A significant proportion of myopic eyes
      had RNFL segmentation errors in automated spectral-domain OCT analysis,
      decreasing glaucoma diagnostic capability of OCT RNFLT measurement.

PMID- 30113514
TI  - Corynebacterium macginleyi-associated Blebitis: A Case Report.
AB  - PURPOSE: The purpose of this study was to report a rare case of
      posttrabeculectomy bleb-related infection associated with Corynebaterium
      macginleyi, a rare conjunctival pathogen. METHODS: Case description including
      clinical imaging and microbiology data, and literature review of Corynebacterium
      macginleyi-related infections. RESULTS: A 60-year-old glaucomatous female patient
      presented with a bleb-related infection 6 years after trabeculectomy in her right
      eye, suggestive of blebitis. No bleb-related endophthalmitis was reported.
      CONCLUSIONS: C. macginleyi is a rare conjunctival pathogen that can cause
      conjunctivitis and, rarely, bleb-related infections.

PMID- 30113515
TI  - Micropulse Versus Continuous Wave Transscleral Cyclophotocoagulation in
      Refractory Pediatric Glaucoma.
AB  - PURPOSE: The aim of this study was to compare the safety and efficacy of
      micropulse cyclophotocoagulation (MP-CPC) and transscleral continuous wave
      cyclophotocoagulation (CW-CPC) for the treatment of refractory glaucoma in the
      pediatric age group. METHODS: This prospective study included 45 eyes of 36
      children requiring transscleral cyclophotocoagulation, in the period spanning
      from September 2016 to August 2017, using micropulse (MP-CPC) or continuous wave
      (CW-CPC) modes. The intraocular pressure (IOP) reduction, success rates, and
      complications were compared for both groups. Success was defined as an IOP of 5
      to 21 mm Hg, in the absence of vision-threatening complications at 6 months.
      RESULTS: The MP-CPC group included 17 eyes, in patients aged 67.8+/-48 months,
      and the CW-CPC group included 28 eyes, in patients aged 61.3+/-38.3 months. There
      was a tendency toward lower IOP in the MP-CPC group at all follow-ups, almost
      reaching statistical significance at 2 weeks and 3 months (P=0.05). IOP reduction
      was 63% in the MP-CPC group and 67% in the CW-CPC group (P=0.6). The success rate
      was higher in the MP-CPC group (71% vs. 46% in the CW-CPC group), but the
      difference was not significant (P=0.1). No significant complications were noted
      in the MP-CPC group whereas, in the CW-CPC group, 1 eye developed phthisis bulbi,
      and 2 eyes had severe pain and uveitis (P=0.3). CONCLUSIONS: Both the MP-CPC and
      CW-CPC are effective in lowering the IOP in children with refractory glaucoma.
      However, the rate of complications, pain, and inflammation seem to be lower with
      the micropulse mode, making it a safer alternative for cyclophotocoagulation,
      especially since retreatments are often needed.

PMID- 30113516
TI  - Ex-PRESS Miniature Glaucoma Shunt Versus Ahmed Glaucoma Valve in the Surgical
      Treatment of Glaucoma in Pseudophakic Patients.
AB  - PURPOSE: The aim of this study was to compare the 3-year outcome of Ex-PRESS
      miniature glaucoma shunt versus Ahmed glaucoma valve in pseudophakic patients.
      PATIENTS AND METHODS: We retrospectively reviewed the records of patients with a
      history of clear corneal phacoemulsification alone, or failed trabeculectomy
      following phacoemulsification, who subsequently underwent Ahmed glaucoma valve
      (AGV) implantation or Ex-PRESS shunt surgery. The main outcome measure, surgical
      success, was defined as an intraocular pressure between 5 and 21 mm Hg and a 20%
      intraocular pressure reduction from baseline (with/without glaucoma medications)
      without glaucoma reoperation. RESULTS: In total, 92 patients (92 eyes) were
      included (43 AGV, 49 Ex-PRESS). Overall success at 3 years was 92.7% for AGV and
      66.1% for Ex-PRESS (P=0.006). AGV had a higher success rate in patients with
      prior phacoemulsification and failed trabeculectomy (96% AGV vs. 64.1% Ex-PRESS;
      P=0.023). There was no difference in success rate for patients with only previous
      phacoemulsification (87.5% AGV vs. 69.4% Ex-PRESS; P=0.205). Glaucoma reoperation
      rates were 4.6% and 30.6% in the AGV and Ex-PRESS group, respectively (P=0.001).
      Both procedures had similar complication rates. CONCLUSIONS: AGV compared with Ex
      PRESS shunt, had a higher success rate for secondary surgeries but not primary
      surgeries, in patients with prior clear corneal phacoemulsification. The AGV
      surgery also had a lower overall glaucoma reoperation rate.

PMID- 30113517
TI  - Intraocular Pressure Lowering Effect of Latanoprost as First-line Treatment for
      Glaucoma.
AB  - PURPOSE: The purpose of this study was to assess the intraocular pressure (IOP) -
      reducing effect of latanoprost in treatment-naive patients with newly detected
      open-angle glaucoma with no restriction of the level of untreated IOP. METHODS:
      Eighty-six patients (105 eyes) with a diagnosis of open-angle glaucoma received
      IOP-lowering therapy with latanoprost. The IOP reduction 1 and 3 months after
      initiation of treatment was recorded. RESULTS: Mean untreated IOP for all eyes
      was 26.2 mm Hg (ranging from 10 to 51 mm Hg). The mean pressure reduction was 7.9
      mm Hg (28%), with equivalent average levels at 1 and 3 months. The reduction in
      IOP ranged from -2.3 to 25.3 mm Hg after 1 month, and from -1.3 to 33.3 mm Hg
      after 3 months. The pressure-lowering effect was considerably more pronounced in
      eyes with higher untreated IOP; the reduction increased by 0.55 mm Hg per mm Hg
      higher untreated IOP. Four eyes, with untreated IOP within statistically normal
      limits, had no or negative IOP-reduction. A regression model predicted that IOP
      reduction ended at untreated IOP<=16 mm Hg. Multiple regression analysis showed
      that an additional IOP-lowering effect of 1.28 mm Hg was achieved in eyes with
      pseudoexfoliation glaucoma. CONCLUSIONS: To the best of our knowledge, this paper
      is the first to report the IOP-reducing effect of latanoprost treatment at all
      untreated IOP levels in newly detected glaucoma patients. The effect was
      proportional to the untreated IOP at all levels above 16 mm Hg and better at
      higher untreated IOP levels, also in relative terms. Our results further confirm
      the indication of latanoprost as a first-line therapy for glaucoma.

PMID- 30113518
TI  - Diagnostic Bedside Ultrasound Program Development in Pediatric Critical Care
      Medicine: Results of a National Survey.
AB  - OBJECTIVES: To assess current diagnostic bedside ultrasound program core element
      (training, credentialing, image storage, documentation, and quality assurance)
      implementation across pediatric critical care medicine divisions in the United
      States. DESIGN: Cross-sectional questionnaire-based needs assessment survey.
      SETTING: Pediatric critical care medicine divisions with an Accreditation Council
      of Graduate Medical Education-accredited fellowship. RESPONDENTS: Divisional
      leaders in education and/or bedside ultrasound training. INTERVENTIONS: None.
      MEASUREMENTS AND MAIN RESULTS: Fifty-five of 67 pediatric critical care medicine
      divisions (82%) with an Accreditation Council of Graduate Medical Education
      accredited fellowship provided responses. Overall, 63% of responding divisions
      (34/54) were clinically performing diagnostic bedside ultrasound studies with no
      difference between divisions with large versus small units. Diagnostic bedside
      ultrasound training is available for pediatric critical care medicine fellows
      within 67% of divisions (35/52) with no difference in availability between
      divisions with large versus small units. Other core elements were present in less
      than 25% of all divisions performing clinical studies, with a statistically
      significant increase in credentialing and documentation among divisions with
      large units (p = 0.048 and 0.01, respectively). All core elements were perceived
      to have not only high impact in program development but also high effort in
      implementation. Assuming that all structural elements could be effectively
      implemented within their division, 83% of respondents (43/52) agreed that
      diagnostic bedside ultrasound should be a core curricular component of fellowship
      education. CONCLUSIONS: Diagnostic bedside ultrasound is increasingly prevalent
      in training and clinical use across the pediatric critical care medicine
      landscape despite frequently absent core programmatic infrastructural elements.
      These core elements are perceived as important to program development, regardless
      of division unit size. Shared standardized resources may assist in reducing the
      effort in core element implementation and allow us to measure important
      educational and clinical outcomes.

PMID- 30113519
TI  - Hepatobiliary Dysfunction and Disseminated Intravascular Coagulation Increase
      Risk of Mortality in Pediatric Hemophagocytic Lymphohistiocytosis.
AB  - OBJECTIVES: Hemophagocytic lymphohistiocytosis poses significant challenges due
      to limited tools to guide clinical decisions in a population at high risk of
      death. We sought to assess whether disseminated intravascular coagulation and
      hepatobiliary dysfunction, significant comorbidities seen in critical care
      settings, would identify hemophagocytic lymphohistiocytosis patients with
      increased risk of mortality. DESIGN: Retrospective chart review. SETTING: Single
      center PICU. PATIENTS: All patients admitted to a tertiary care children's
      hospital diagnosed with hemophagocytic lymphohistiocytosis from 2005 to 2012.
      INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Forty-three patients were
      diagnosed with hemophagocytic lymphohistiocytosis with median age of 61 months.
      The 5-year overall survival was 51% (22/43). Univariate analyses revealed
      ferritin levels greater than 10,000 (ng/mL), international normalized ratio
      greater than 1.5, or platelet counts less than 100,000/uL at initiation of
      dexamethasone were individually associated with mortality. Development of
      disseminated intravascular coagulation, hepatobiliary dysfunction, or both
      increased the likelihood of death in hemophagocytic lymphohistiocytosis patients
      (relative risk; 95% CI) (6; 1.4-34; p < 0.05), (4.1; 1.8-10; p < 0.05), and (7.5;
      1.8-42; p < 0.05). Of 12 autopsies performed, 75% had at least one active
      infection, 66% had chronic lymphopenia, 50% had lymphocyte depletion in the
      spleen, thymus, or bone marrow, 42% had evidence of microvascular thrombosis, and
      92% had evidence of hepatocellular injury. CONCLUSIONS: Hemophagocytic
      lymphohistiocytosis continues to have high mortality with hemophagocytic
      lymphohistiocytosis-1994/2004 (dexamethasone/etoposide), the current standard of
      care for all children with hemophagocytic lymphohistiocytosis. Hemophagocytic
      lymphohistiocytosis patients who developed disseminated intravascular
      coagulation, hepatobiliary dysfunction, or both had higher risk of death with
      mortalities of 60%, 77%, and 77%, respectively. Phenotypic classifications are
      urgently needed to guide individualized treatment strategies to improve outcomes
      for children with hemophagocytic lymphohistiocytosis.

PMID- 30113521
TI  - Walking in Minimalist Shoes Is Effective for Strengthening Foot Muscles.
AB  - INTRODUCTION: Weakness of foot muscles may contribute to a variety of loading
      related injuries. Supportive footwear may contribute to intrinsic foot muscle
      weakness by reducing the muscles' role in locomotion (e.g. absorbing forces and
      controlling motion). Increased stimulus to the foot muscles can be provided
      through a variety of mechanisms, including minimalist footwear and directed
      exercise. PURPOSE: To determine the effect of walking in minimalist footwear or
      performing foot strengthening exercises on foot muscle size and strength.
      RESULTS: In study 1, genotype frequencies for ESR1 rs2234693 were significantly
      different between the injured and non-injured groups in a C-allele dominant
      (CC+CT vs. TT: odds ratio [OR] = 0.62, 95% confidence interval [CI] = 0.43-0.91)
      and additive (CC vs. CT vs. TT: OR = 0.70, 95% CI = 0.53-0.91) model in all
      athletes. In study 2, hamstring muscle stiffness was lower in subjects with the
      CC+CT genotype than in those with the TT genotype; a significant linear trend was
      found (r = 0.135, P = 0.029). In contrast, no associations were observed between
      ESR1 rs9340799 G/A and muscle injury or stiffness. METHODS: Fifty-seven runners
      were randomly assigned to one of three groups - minimalist shoe walking (MSW),
      foot strengthening exercise (FS), or control (C). All groups maintained their pre
      study running mileage throughout the study. The MSW group walked in provided
      footwear, increasing weekly the number of steps/day taken in the shoes. The FS
      group performed a set of progressive resistance exercises at least 5 days/week.
      Foot muscle strength (via custom dynamometers) and size (via ultrasound) were
      measured at the beginning (week 0), middle (week 4), and end (week 8) of the
      study. Mixed model ANOVAs were run to determine if the interventions had
      differing effects on the groups.Single nucleotide polymorphism; estrogen
      receptor; muscle stiffness; injury prediction; athletes RESULTS: There were
      significant group by time interactions for all muscle size and strength
      measurements. All muscle sizes and strength increased significantly from weeks 0
      8 in the FS and MSW groups, while there were no changes in the C group. Some
      muscles increased in size by week 4 in the FS and MSW groups.Single nucleotide
      polymorphism; estrogen receptor; muscle stiffness; injury prediction; athletes
      CONCLUSION: Minimalist shoe walking is as effective as foot strengthening
      exercises in increasing in foot muscle size and strength. The convenience of
      changing footwear rather than performing specific exercises may result in greater
      compliance.

PMID- 30113520
TI  - ESR1 rs2234693 Polymorphism Is Associated with Muscle Injury and Muscle
      Stiffness.
AB  - PURPOSE: Muscle injury is the most common sports injury. Muscle stiffness, a risk
      factor for muscle injury, is lower in females than in males, implying that sex
      related genetic polymorphisms influence muscle injury associated with muscle
      stiffness. The present study aimed to clarify the associations between two
      genetic polymorphisms (rs2234693 and rs9340799) in the estrogen receptor 1 gene
      (ESR1) and muscle injury or muscle stiffness. METHODS: In study 1, a
      questionnaire was used to assess the muscle injury history of 1,311 Japanese top
      level athletes. In study 2, stiffness of the hamstring muscles was assessed using
      ultrasound shear wave elastography in 261 physically active young adults. In both
      studies, rs2234693 C/T and rs9340799 G/A polymorphisms in the ESR1 were analysed
      using the TaqMan SNP Genotyping Assay. RESULTS: In study 1, genotype frequencies
      for ESR1 rs2234693 were significantly different between the injured and non
      injured groups in a C-allele dominant (CC+CT vs. TT: odds ratio [OR] = 0.62, 95%
      confidence interval [CI] = 0.43-0.91) and additive (CC vs. CT vs. TT: OR = 0.70,
      95% CI = 0.53-0.91) model in all athletes. In study 2, hamstring muscle stiffness
      was lower in subjects with the CC+CT genotype than in those with the TT genotype;
      a significant linear trend was found (r = 0.135, P = 0.029). In contrast, no
      associations were observed between ESR1 rs9340799 G/A and muscle injury or
      stiffness. CONCLUSION: Our results suggest that the ESR1 rs2234693 C allele, in
      contrast to the T allele, provides protection against muscle injury by lowering
      muscle stiffness.Single nucleotide polymorphism; estrogen receptor; muscle
      stiffness; injury prediction; athletes.

PMID- 30113522
TI  - Equivalent Hypertrophy and Strength Gains in HMB- or Leucine-supplemented Men.
AB  - : Ingestion of proteins with high leucine content during resistance training (RT)
      can augment hypertrophy. Some data suggest that a leucine metabolite, beta
      hydroxy, beta-methylbutyrate (HMB), is substantially more anabolically
      efficacious than leucine. PURPOSE: We aimed to test whether supplementation with
      HMB versus leucine, added to whey protein, would result in differential muscle
      hypertrophy and strength gains in young men performing resistance training.
      METHODS: Twenty-six resistance-trained men (23 +/- 2 y) performed 12 wk of RT
      with 3 phases. Phase 1: 8 wk of periodized RT (3 training sessions/wk). Phase 2:
      2 wk overreaching period (5 sessions/wk). Phase 3: 2 wk taper (3 sessions/wk).
      Participants were randomly assigned to twice daily ingestion of: whey protein (25
      g) plus HMB (1.5 g) (Whey+HMB; n=13) or whey protein (25 g) plus leucine (1.5 g)
      (Whey+Leu; n=13). Skeletal muscle biopsies were performed before and after RT.
      Measures of fat and bone-free mass (FBFM), vastus lateralis (VL) muscle thickness
      and muscle cross-sectional area (CSA - both by ultrasound), muscle fiber CSA, and
      1-repetition maximum (1-RM) strength tests were determined. RESULTS: We observed
      increases in FBFM, VL muscle thickness, muscle CSA and fiber type CSA and 1-RM
      strength with no differences between groups at any phase. We observed no
      differences between groups or time-by-group interactions in hormone
      concentrations at any phase of the RT program. CONCLUSION: HMB added to whey did
      not result in greater increases in any measure of muscle mass, strength, or
      hormonal concentration compared to leucine added to whey. Our results show that
      HMB is no more effective in stimulating RT-induced hypertrophy and strength gains
      than leucine.

PMID- 30113523
TI  - Augmented Anabolic Responses following 8-weeks Cycling with Blood Flow
      Restriction.
AB  - INTRODUCTION: Low-intensity endurance training performed with blood flow
      restriction (ET-BFR) can improve muscle strength, cross-sectional area (CSA) and
      cardiorespiratory capacity. Whether muscle strength and CSA as well as
      cardiorespiratory capacity (i.e.:VO2max) and underlying molecular processes
      regulating such respective muscle adaptations are comparable to resistance and
      endurance training is unknown. PURPOSE: To determine the respective chronic
      (i.e.: 8 weeks) functional, morphological and molecular responses of ET-BFR
      training compared to conventional, unrestricted resistance training (RT) and
      endurance training (ET). METHODS: Thirty healthy young men were randomly assigned
      to one of three experimental groups: ET-BFR (n=10, 4 days/wk, 30 min cycling at
      40% of VO2max), RT (n=10, 4 days/wk, 4 sets of 10 reps leg-press at 70% of 1-RM
      with 60 s rest) or ET (n=10, 4 days/wk, 30 min cycling at 70% of VO2max) for 8
      weeks. Measures of quadriceps CSA, leg press 1-RM, and VO2max as well as muscle
      biopsies were obtained prior to and post intervention. RESULTS: Both RT and ET
      BFR increased muscle strength and hypertrophy responses. ET-BFR also increased
      VO2max, total COXIV abundance and VEGF mRNA abundance despite the lower work load
      compared to ET. CONCLUSION: Eight weeks of ET-BFR can increase muscle strength
      and induce similar muscle hypertrophy responses to RT while VO2max responses also
      increased post-intervention even with a significantly lower work load compared to
      ET. Our findings provide new insight to some of the molecular mechanisms
      mediating adaptation responses with ET-BFR and the potential for this training
      protocol to improve muscle and cardiorespiratory capacity.

PMID- 30113524
TI  - Predictors of Dropout in Exercise Trials in Older Adults.
AB  - PURPOSE: Dropout from exercise programs, both in the real world and in research,
      is a challenge, and more information on dropout-predictors is needed for
      establishing strategies to increase the likelihood of maintaining participants in
      a prescribed exercise program. The aim of the present study was to determine the
      dropout rate and its predictors during a 3-year exercise program in older adults.
      METHODS: In total, 1514 men and women (age 72.4+/-1.9 years) were included in the
      present study. Participants were randomized to either a supervised exercise
      intervention or to follow national guidelines for physical activity (PA). Self
      reported demographics (e.g. education), general health, morbidity (e.g. heart
      disease, memory loss, psychological distress), smoking and PA were examined at
      baseline. Cardiorespiratory fitness (CRF) and grip strength were directly
      measured at baseline. Dropout rate was evaluated after 1- and 3-years.
      Multivariate logistic regression analysis was used to identify dropout
      predictors. RESULTS: The total dropout rate was 11.0% (n=166) after 1-year and
      14.9% (n=225) after 3-years. Significant predictors of dropout after 1-year were
      low education, low grip strength, lower CRF, low PA level and randomization to
      supervised exercise. The same predictors of dropout were significant after 3
      years, with reduced memory status as an additional predictor. CONCLUSION: This is
      the largest study to identify dropout-predictors in a long-term exercise program
      in older adults. Our findings provide new and important knowledge about potential
      risk factors of dropout in long-term exercise programs in older adults.

PMID- 30113525
TI  - Range of Extension Correlates with Posterior Capsule Length after Knee
      Remobilization.
AB  - INTRODUCTION: Knee injuries are common in sports, and postinjury immobilization
      is often required to protect healing tissues and alleviate pain, but both the
      injury and the immobilization can lead to a knee contracture. Knee flexion
      contractures limit performance. Previous research has identified posterior knee
      capsule fibrosis as a contributor to immobility-induced knee flexion
      contractures. This study aims to measure posterior knee capsule length at various
      durations of remobilization after knee immobilization and to correlate with the
      recovery of knee range of motion. METHODS: Two hundred fifty-nine male Sprague
      Dawley rats had one knee extra-articularly immobilized in flexion with a
      Delrin(r) plate at a 45 degrees  angle for one of six durations: 1, 2, 4, 8, 16,
      or 32 wk, followed by spontaneous remobilization after plate removal, which
      lasted zero, one, two, and four times the duration of immobilization. The
      contralateral knees served as controls. The posterior knee capsule length was
      measured by histomorphometry. These measures were correlated with previously
      published range of motion data from the same cohort of specimens. RESULTS: Knees
      immobilized for 1 and 2 wk partially recovered posterior capsule length (P >
      0.05). Knees immobilized beyond 2 wk failed to recover posterior capsule length,
      irrespective of the duration of remobilization (P < 0.05). The residual posterior
      capsule shortening correlated with the lack of knee extension (P < 0.003).
      CONCLUSIONS: For knee injuries requiring more than 2 wk of immobilization,
      unassisted remobilization will not restore posterior knee capsule shortening and
      the reduction in knee extension. These results support the role of the posterior
      capsule in knee joint contracture and the need to minimize the duration of
      immobility and to assist the recovery of the range of knee extension after a
      sport injury.

PMID- 30113526
TI  - Diabetic patients with essential hypertension treated with amlodipine: blood
      pressure and arterial stiffness effects of canagliflozin or perindopril.
AB  - INTRODUCTION: Hypertension control reduces cardiovascular and renal risks in type
      2 diabetes. Sodium-glucose cotransporter-2 inhibitors prevent renal glucose
      reabsorption and decrease glucose plasma levels, blood pressure (BP) and weight
      reduction. Treatment of hypertension and sodium-glucose cotransporter-2 are able
      to improve arterial stiffness. AIMS: To evaluate, in patients with type 2
      diabetes and hypertension, the effects of 6 months treatment with canagliflozin,
      or perindopril, an angiotensin converting enzyme inhibitor, on central BP and
      carotid-femoral pulse wave velocity (cfPWV). METHODS: Thirty type 2 diabetic
      patients with hypertension taking amlodipine, 10 mg daily, and metformin, 750
      2000 mg daily, were randomized and a third medication was added: canagliflozin,
      300 mg daily (n = 15, nine women, mean age: 63 +/- 8 years), or perindopril, 10
      mg daily (n = 15, five women, mean age 59 +/- 4 years), for 6 months. Ambulatory
      BP monitoring was assessed at baseline and after 3 and 6 months of treatment,
      whereas cfPWV was measured before and after 6 months of treatment. Plasma fasting
      glucose, glycated hemoglobin, creatinine, plasma and urinary sodium and potassium
      were also measured. RESULTS: Both treatments significantly reduced BP and cfPWV.
      Only canagliflozin maintained the PWV action after adjusting for BP values and
      reduced glycemia, glycated hemoglobin and 24 h urinary sodium. Other security
      laboratory parameters, including gluthamic oxaloacetic transaminase, gluthamic
      piruvic transaminase; and bilirubin failed to show any change. CONCLUSION:
      Canagliflozin reduced BP and improve arterial stiffness, independently of the BP
      effect. These two conditions could explain the cardiovascular protection observed
      with canagliflozin compared with perindopril.

PMID- 30113528
TI  - Change in left ventricular geometry over 10 years in the elderly and risk of
      incident cardiovascular disease.
AB  - OBJECTIVE: Left ventricular hypertrophy (LVH) is related to a poor prognosis. We
      aimed to determine how left ventricular (LV) geometry changes over time, and how
      this relates to future cardiovascular disease. METHODS: In the Prospective Study
      of the Vasculature in Uppsala Seniors study, 1016 individuals were investigated
      with echocardiography at age 70. This was repeated after 5 and 10 years. Incident
      cardiovascular disease (myocardial infarction, stroke, and heart failure, n =
      163) was recorded over 10 years. RESULTS: LV mass index (LVMI) and LV end
      diastolic diameter (LVEDD) progressively increased over 10 years, while LV
      thickness declined (P < 0.0001 for all). Adjusting for traditional cardiovascular
      risk factors, LVMI at baseline, but not LVEDD, was significantly associated with
      incident cardiovascular disease [hazard ratio (HR) 1.02, 95% confidence interval
      1.003-1.03, P = 0.019]. When adding the change in LVMI, or change in LVEDD,
      between ages 70 and 75 years to the models and using the time between 75 and 80
      as follow-up (in total 82 incident cases), neither the change in LVMI nor the
      change in LVEDD were significant. Using updated information on LV geometric
      groups, an increased risk was seen for concentric LVH as compared with the normal
      group following adjustment for traditional risk factors (HR 2.29, P = 0.0014, 95%
      confidence interval 1.38-3.82). Eccentric LVH and concentric remodeling were not
      associated with a statistically significant increased risk of cardiovascular
      disease. CONCLUSION: In elderly individuals without myocardial infarction, a
      progressive dilatation of the LV was seen over 10 years. However, the LV dilation
      seen over time in this age group was not associated with a major increase in risk
      of future cardiovascular disease.

PMID- 30113527
TI  - Application of a central iliac arteriovenous coupler device in severe treatment
      resistant hypertension: a 3.5-year follow-up.
AB  - OBJECTIVE: In patients with resistant hypertension, percutaneous placement of an
      iliac arteriovenous coupler device leads to a reduction of blood pressure (BP)
      via decreased total vascular resistance and improved arterial compliance.
      However, long-term efficacy and safety need to be further explored. We report on
      the first case of 3.5-year follow-up in a patient who underwent implantation of
      an iliac arteriovenous coupler device. RESULTS: A patient with resistant
      hypertension was admitted to hospital. Despite treatment with six anti
      hypertensive drugs, his BP was poorly controlled. Previously, he had undergone
      renal denervation, which did not cause a significant BP decrease. Therefore, an
      arteriovenous coupler device was implanted, leading to an immediate and
      significant BP decrease. The patient was discharged with an office BP of 122/71
      mmHg. After 3 months, there was a sustained BP decrease (-14/9 mmHg), whereas
      later, it was fluctuant (office BP: 147-173/85-95 mmHg, ABPM: 153-166/81-94 mmHg)
      probably due to medication non-adherence confirmed by a urinary toxicological
      screening test. Follow-up right heart catheterization showed changes in
      hemodynamic parameters related to volume congestion, which were accompanied by
      progressive dyspnea and weight gain. This was controlled by an optimized diuretic
      therapy. Additionally, an invasive closure maneuver was performed, leading to an
      immediate BP increase after closure and a similar decrease after re-opening of
      the anastomosis, verifying its proper long-term function. CONCLUSION: The
      implantation of an iliac arteriovenous coupler device appears to be a promising
      and effective method to decrease BP and therefore reduce cardiovascular risk in
      patients with severe, treatment-resistant hypertension.

PMID- 30113529
TI  - Do treatment-induced changes in arterial stiffness affect left ventricular
      structure? A meta-analysis.
AB  - BACKGROUND: Vascular research demonstrated that pulse wave velocity (PWV), a
      measure of arterial stiffness, is inherently blood pressure dependent.
      Considering the hypothesized pathophysiological chain of increased arterial
      stiffness leading to increased blood pressure load with consequent left
      ventricular hypertrophy (LVH) development, we conducted a systematic review of
      antihypertensive and lifestyle intervention studies to determine the association
      between, on the one hand, changes in arterial stiffness and blood pressure, and,
      on the other hand, changes in left ventricular mass (LVM). METHODS: Using PubMed,
      EMBASE, Cochrane and Web of Science, we identified 23 studies, containing 2573
      patients. Studies reported changes in arterial stiffness (assessed by means of
      PWV), SBP, DBP and LVM index (LVMI), respectively. RESULTS: Statistically
      significant reductions in SBP, PWV and LVMI were reported in 16, 14 and 20
      studies, respectively. Pooled analysis of studies showed that the proportion in
      SBP reduction did not correlate significantly to the proportion in reductions of
      the other two variables. On the contrary, we found a significant positive
      correlation (r = 0.61, P = 0.003) between arterial stiffness and reduction of
      LVM, expressed as a relevant reduction in LVMI of 6.9 g/m per 1.0 m/s reduction
      in PWV. CONCLUSION: Our findings provide evidence that a decrease in arterial
      stiffness is associated with reduction of LVM. To investigate whether there
      exists a causal relation between LVH due to arterial stiffness increases and in
      turn blood pressure load increases, future studies should strive for a multiple
      follow-up design and use of blood pressure independent or corrected stiffness
      indices.

PMID- 30113530
TI  - Impact of hypertension on retinal capillary microvasculature using optical
      coherence tomographic angiography.
AB  - OBJECTIVE: Reduction in capillary density or rarefaction is a hallmark of
      essential hypertension. We measured the retinal capillary density using
      noninvasive optical coherence tomographic angiography (OCT-A) in adults with
      treated systemic hypertension and determined possible correlations with
      ambulatory blood pressure (BP) and renal parameters. METHODS: This observational
      cross-sectional study consisted of 153 normal eyes from 77 nondiabetic
      hypertensive adults [mean (SD) age, 58 (9) years; 49% women; 23% poorly
      controlled BP]. Data on 24-h ambulatory BP monitoring, serum creatinine, and
      urine microalbumin/creatinine ratio (MCR) were collected. Estimated glomerular
      filtration rate (eGFR) was calculated based on CKD-EPI Creatinine Equation.
      Retinal capillary density measured with the OCT-A (AngioVue) at superficial (SVP)
      and deep vascular plexuses (DVP). Linear regression was used to investigate the
      association of risk factors with capillary density. RESULTS: Retinal capillary
      density (percentage) at DVP was reduced in patients with poorly controlled BP
      (SBP = 148 +/- 8 mmHg; 27.2 +/- 13.0) compared with those with well controlled BP
      (SBP = 125 +/- 9 mmHg; 34.7 +/- 11.3). In the multivariable analysis, poorly
      controlled BP [beta = -6.49, 95% confidence interval (CI), -12.39 to -0.59],
      higher SBP (beta = -0.23, 95% CI -0.44 to -0.02) and lower eGFR (beta = 6.42, 95%
      CI 1.25-11.60) were associated with sparser retinal capillary density. Systemic
      factors were not associated with capillary density at SVP (all P > 0.05).
      CONCLUSION: In adults with treated systemic hypertension, retinal capillary
      density reduced with higher BP and poorer eGFR. These findings highlight the
      potential role of OCT-A to study early microvascular changes because of systemic
      hypertension.This is an open access article distributed under the terms of the
      Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC
      ND), where it is permissible to download and share the work provided it is
      properly cited. The work cannot be changed in any way or used commercially
      without permission from the journal. http://creativecommons.org/licenses/by-nc
      nd/4.0.

PMID- 30113531
TI  - Health care providers' perceptions regarding fundamental issues to consider prior
      to launching nurse practitioner training in Tanzania.
AB  - BACKGROUND AND PURPOSE: Although the demand for competent health care
      professionals and better services is high, studies concerning nursing education
      are not a priority in sub-Saharan African countries, as revealed in limited
      available records. Strengthening nursing education by establishing proper
      training models for newly developed advanced practice roles such as "nurse
      practitioner" (NP) will increase competency in nurses and reduce the shortage of
      skilled staff within the health care system, thereby enhancing the proper
      provision of health care services. The main purpose of this research was to
      investigate fundamental issues that should be considered in the launching of NP
      training. METHODS: A descriptive qualitative design was used in this study. A
      nonprobability sampling approach and significantly purposeful sampling were also
      used to recruit 20 health care providers into the study. Individual face-to-face
      interviews were conducted on scheduled timings, which required an average of 30
      minutes for each interview. Finally, a content analysis was used to identify the
      themes. CONCLUSION: The current working environment at the rural primary health
      care facilities is not convenient for the practices of NPs trained at the
      master's level. Therefore, before the training of NPs, the government and all
      stakeholders should strive to improve the environment of the facilities including
      adequate diagnostic equipment and on-time supply of drugs from the store.
      Institutions aiming to introduce programs for NPs must develop their curriculum
      based on currently available local and international guidelines. IMPLICATIONS FOR
      PRACTICE: Adequate preparation before launching an NP training program will be
      needed to help build a strong training and hence produce competent professionals.

PMID- 30113532
TI  - The impact of interprofessional education on family nurse practitioner students'
      and family medicine residents' knowledge and confidence in screening for breast
      and cervical cancer.
AB  - BACKGROUND AND PURPOSE: This study determined the impact of an interprofessional
      education (IPE) simulation on family nurse practitioner (FNP) students' and
      family medicine residents' (FMRs) self-reported confidence in counseling women
      reluctant to engage in cancer screening or evaluation and assessed knowledge of
      breast and cervical cancer risk factors. METHOD: A multi-item knowledge survey on
      breast and cervical cancer risk factors was administered to 76 FNP students and
      FMRs followed by an IPE simulation with a pre-/postsurvey of self-reported
      confidence in counseling a woman reluctant to have breast and cervical cancer
      screening and evaluation. DISCUSSION: Data demonstrated knowledge deficits in
      breast and cervical cancer risk factors in both disciplines with the average risk
      factor knowledge score of 8.5/12 for breast cancer and 7.8/12 for cervical
      cancer. Following IPE simulation, confidence in counseling women reluctant to
      have breast or cervical cancer screening improved across both disciplines (p <
      .05) and debrief feedback findings suggest improved attitudes toward
      collegiality, communication, and understanding of other interprofessional roles
      among both disciplines. CONCLUSION: Knowledge gaps exist among both FNP students
      and FMRs in breast and cervical cancer risk factors. This study suggests IPE
      simulation is effective in building individual provider confidence and team
      collegiality.

PMID- 30113533
TI  - Nurse practitioners' time on nonbillable activities.
AB  - BACKGROUND AND PURPOSE: During the provision of patient care delivery, all
      providers, including nurse practitioners (NPs), spend some time in activities
      that are not reimbursable. Understanding these nonbillable activities is crucial
      to the economic viability and success of existing and projected practice models.
      This study explored and compared seven nonbillable activities occurring in the
      practices of NPs in various settings. METHODS: Using a nonexperimental,
      descriptive design, 509 NPs were surveyed about nonbillable activities
      encountered in daily practice. Binomial regression analyses and incidence rate
      ratios were used to interpret relationships between each variable and nonbillable
      time. CONCLUSIONS: Although not every variable had significance, there were
      significant differences found in the amount of time spent in certain nonbillable
      activities depending on workplace setting, number of support staff, and primary
      care provider role. IMPLICATIONS FOR PRACTICE: The uncertainty of health care
      reform, including reimbursement, provider shortage, and the expanding roles of
      NPs, requires a closer look at both billable and nonbillable care activities.
      Understanding how nonbillable time affects work efficiency, costs, and the value
      of NPs will allow NPs to influence future health care reimbursement policies and
      delivery care models.

PMID- 30113534
TI  - Nurse practitioners' recommendations for pharmacotherapy in the management of
      adolescent concussion.
AB  - BACKGROUND AND PURPOSE: Nurse practitioners (NPs) frequently treat acute
      conditions presenting in children and adolescents in the outpatient setting. No
      evidence-based guidance exists pertaining to the treatment of concussion with
      medications. The purpose of this study was to examine recommendations by NPs for
      pharmacotherapy of acute symptoms for adolescent concussion. METHODS: This is a
      secondary analysis of data from a web-based census survey of all licensed NPs in
      Oregon and Washington State, where they practice as independent providers with
      prescriptive authority. Based on a standardized adolescent patient scenario
      video, NPs were asked to indicate prescription or nonprescription medication
      recommendations for concussion symptoms. Open-ended descriptions of medication
      recommendations were coded, summarized, and described. CONCLUSIONS: In narrative
      text, 78.4% of the 991 respondents recommended at least one type of prescription
      or nonprescription medication. Prescription medications (recommended by 17.2%)
      included antiemetics and antimigraine medications; nonprescription medications
      (recommended by 75.5%) included nonsteroidal anti-inflammatory drugs, over-the
      counter pain relievers, and herbal medications. Pharmacotherapy recommendations
      varied by NP practice setting and rurality. IMPLICATIONS FOR PRACTICE: Nurse
      practitioners have full prescriptive authority in many states. No guidelines
      inform medication use in managing acute concussion symptoms, yet many providers
      recommend their use.

PMID- 30113535
TI  - The Effectiveness of Full-body EOS Compared With Conventional Chest X-ray in
      Preoperative Evaluation of the Chest for Patients Undergoing Spine Operations: A
      Preliminary Study.
AB  - STUDY DESIGN: A prospective radiographic comparative study. OBJECTIVE: The aim of
      this study was to compare full-body EOS with conventional chest X-ray (CXR) for
      use in the preoperative evaluation of the chest in patients undergoing spine
      operations. SUMMARY OF BACKGROUND DATA: The full-body EOS reproduces an image of
      the chest similar to a routine CXR. The potential for the former replacing the
      latter is plausible. This is especially applicable in spine patients who would
      routinely have a preoperative full-body EOS performed. METHODS: A radiographic
      comparative study of 266 patients was conducted at a single tertiary center from
      January 2013 to July 2016. Each patient had EOS and CXR done in random order <2
      weeks apart. Two radiologists reported the image findings using a checklist. A
      third radiologist was consulted in cases of discrepancy. Interobserver agreement
      was calculated using Gwet AC1 and a comparison between EOS and CXR findings was
      analyzed using paired Chi-squared test. Multivariate analysis was performed to
      identify predictors for abnormal radiological findings. The institutional ethics
      committee approved this prospective study and waiver of informed consent was
      obtained. RESULTS: There were 84 males (31.6%) and 182 females (68.4%). The mean
      age was 38.9 years (SD = 25.0 years). High interobserver agreement was found for
      EOS and CXR (Gwet AC1 0.993 and 0.988, respectively). There were no significant
      differences between both imaging modalities. Rare diagnoses precluded comparison
      of certain conditions. Age >18 years [odds ratio (OR) 7.69; P = 0.009] and
      American Society of Anesthesiologists physical status 3 (OR 6.64; P = 0.018) were
      independent predictors of abnormal radiological findings. CONCLUSION: EOS is not
      inferior to, and may be used to replace CXR in preoperative radiological
      screening of thoracic conditions especially in low-risk patients <=18 years old
      and patients with ASA <3. Preoperative assessment should never rely on a single
      modality. High-risk patients should be sent for a thorough work-up before spine
      surgery. LEVEL OF EVIDENCE: 4.

PMID- 30113536
TI  - Validation of the Dutch-Flemish PROMIS Pain Interference Item Bank in Patients
      With Musculoskeletal Complaints.
AB  - STUDY DESIGN: Cross sectional study. OBJECTIVE: To validate the Dutch-Flemish
      PROMIS Pain Interference item bank in patients with musculoskeletal complaints.
      SUMMARY OF BACKGROUND DATA: PROMIS item banks have been developed and validated
      in the US. They need to be further validated in various patient populations and
      in different languages. METHODS: 1677 patients answered the full item bank. A
      Graded Response Model (GRM) was used to study dimensionality with confirmatory
      factor analyses and by assessing local independency. Monotonicity was evaluated
      with Mokken scaling. An IRT model was used to study item fit, and to estimate
      slope and threshold parameters. Differential Item Functioning (DIF) for language,
      age and gender was assessed using ordinal logistic regression analyses. DIF for
      language was evaluated by comparing our data with a similar US sample. Hypotheses
      concerning construct validity were tested by correlating item bank-scores with
      scores on several legacy instruments. RESULTS: The GRM showed suboptimal evidence
      of unidimensionality in confirmatory factor analysis (CFI: 0.903, TLI: 0.897,
      RSMEA: 0.144), and 99 item pairs with local dependence. A bi-factor model showed
      good fit (CFI: 0.964, TLI: 0.961, RSMEA: 0.089), with a high Omega-H (0.97), a
      high Explained Common Variance (ECV: 0.81), and no local dependence. Sufficient
      monotonicity was shown for all items (Mokken H(i): 0.367-0.686). The
      unidimensional IRT model showed good fit (Only two items with S-X < 0.001), with
      slope parameters ranging from 1.00 to 4.27, and threshold parameters ranging from
      -1.77 to 3.66. None of the items showed DIF for age or gender. One Item showed
      DIF for language. Correlations with legacy instruments were high (Pearson's R:
      0.53-0.75), supporting construct validity. CONCLUSION: The high omega-H and the
      high ECV indicate that the item bank could be considered essentially
      unidimensional. The item bank showed good item fit, good coverage of the pain
      interference trait, and good construct validity. LEVEL OF EVIDENCE: N/A.

PMID- 30113537
TI  - Community-associated Methicillin-Resistant Staphylococcus aureus Infection Rates
      and Management among Student-Athletes.
AB  - PURPOSE: Although community-associated methicillin-resistant Staphylococcus
      aureus (CA-MRSA) infections have reduced among inpatient populations, the
      incidence in athletics continues to range greatly dependent on the sport. Over
      the 2015 to 2016 and 2016 to 2017 school years, we assessed the annual CA-MRSA
      incidence, sport risk, referral practices, and management protocols or
      interventions among high school and intercollegiate athletics. METHODS: This
      study targeted high school and intercollegiate athletic programs across the
      United States. For the 2015 to 2016 study, 269 athletic trainers completed a one
      time questionnaire. In the 2016 to 2017 study, 217 athletic trainers reported
      data bimonthly during the academic year. Each questionnaire targeted demographic
      information, physician-confirmed CA-MRSA infection occurrence, and management of
      CA-MRSA infections and bacterial skin lesions. RESULTS: The CA-MRSA infection
      incidence was 26.8 per 10,000 athletes (95% confidence interval [CI], 24-30) in
      2015-2016 and 20.3 per 10,000 athletes (95% CI, 18-23) in 2016-2017. The CA-MRSA
      infection incidence was high in wrestling and football compared to the general
      student-athlete population. During the 2015 to 2016 study, the wrestling
      incidence rate was 248.3 per 10,000 (95% CI, 204-302); the football incidence
      rate was 71.0 per 10,000 (95% CI, 60-85). In the 2016 to 2017 study, the
      wrestling incidence rate was 100.0 per 10,000 (95% CI, 66-151); the football
      incidence rate was 81.8 per 10,000 (95% CI, 68-99). At least 23% of respondents
      denoted at least one physician-confirmed CA-MRSA infection within their
      populations (2015-2016, 39%, n = 105; 2016-2017, 23.5%, n = 51). In the 2015 to
      2016 survey, respondents indicated that athlete education and environmental
      decontamination were the most used management steps (51.8%, n = 582).
      CONCLUSIONS: Despite increased awareness of CA-MRSA, more educational efforts
      focusing on best practices and education are needed, especially with athletes and
      the medical community involved in their care.

PMID- 30113539
TI  - Heat Loss Is Impaired in Older Men on the Day after Prolonged Work in the Heat.
AB  - PURPOSE: Prolonged work in the heat may exacerbate the rise in core temperature
      on the next work day, especially in older workers who display impairments in
      whole-body heat loss that increase body heat storage and core temperature
      relative to young adults during heat stress. We therefore evaluated whether whole
      body heat loss in older adults was impaired on the day after prolonged work in
      the heat. METHODS: Whole-body heat exchange and heat storage were assessed in
      nine older (53-64 yr) men during three 30-min bouts of semirecumbent cycling at
      fixed rates of metabolic heat production (150 [Ex1], 200 [Ex2], 250 W.m [Ex3]),
      each separated by 15-min recovery, in hot-dry conditions (40 degrees C, 20%
      relative humidity), immediately before (day 1), and on the day after (day 2) a
      prolonged, work simulation (~7.5 h) involving moderate-intensity intermittent
      exercise in hot-dry conditions (38 degrees C, 34% relative humidity). Total heat
      loss (evaporative +/- dry heat exchange) and metabolic heat production were
      measured using direct and indirect calorimetry, respectively. Body heat storage
      was quantified as the temporal summation of heat production and loss. RESULTS:
      Total heat loss (mean +/- SD) during Ex1 did not differ between days 1 and 2 (151
      +/- 15 and 147 +/- 14 W.m, respectively; P = 0.27), but was attenuated on day 2
      during Ex2 (181 +/- 15 W.m) and Ex3 (218 +/- 16 W.m) relative to day 1 (192 +/-
      14 and 230 +/- 19 W.m, respectively; both P < 0.01). Consequently, body heat
      storage throughout the protocol on day 2 (276 +/- 114 kJ) was 31% greater than on
      day 1 (191 +/- 87 kJ; P < 0.01). CONCLUSIONS: Prolonged work in the heat causes
      next-day impairments in whole-body heat loss, which exacerbate heat storage and
      may elevate the risk of heat injury on the following day in older workers.

PMID- 30113540
TI  - Bed Rest Studies as Analogs of Conditions Encountered in Space and in Diseases.

PMID- 30113541
TI  - Synthesizing complex neonatal health intervention research in low- and middle
      income countries: should we be doing it with a "grain of salt"?

PMID- 30113538
TI  - Benefits of 8-wk Mindfulness-based Stress Reduction or Aerobic Training on
      Seasonal Declines in Physical Activity.
AB  - : Mindfulness-based stress reduction (MBSR) and aerobic exercise training (AET)
      programs improve health and well-being. Exercise participation has been related
      to mindfulness and may be altered by MBSR training. PURPOSE: This study aimed to
      compare 8 wk of MBSR, AET, and no-treatment control during the fall season on
      objectively measured physical activity in healthy adults. METHODS: Participants
      (n = 66) wore an ActiGraph GT3X+ accelerometer for 7 d prerandomization and after
      8 wk MBSR or AET interventions, or neither (control). Mean daily minutes (min) of
      moderate-to-vigorous physical activities (MVPA) were calculated along with weekly
      time spent in bouts of MVPA >=10 min (MVPABouts) to assess physical activity
      sufficient to meet national guidelines. Groups were compared on pairwise changes
      in outcomes across time. Effect sizes were calculated using Cohen's d. RESULTS:
      Sufficient data (>=3 weekdays, >=1 weekend day, and >=10 h.d) were obtained from
      49 participants (18 MBSR, 14 AET, and 17 control). Daily MVPA decreased in all
      groups from prerandomization to postintervention (August to November); control
      decreased 17.9 +/- 25.7 min.d, MBSR decreased 5.7 +/- 7.5 min.d, and AET
      decreased 7.4 +/- 14.3 min.d (mean +/- SD), without significant differences among
      the groups (all P > 0.05). MVPABouts decreased 77.3 +/- 106.6 min.wk in control
      and 15.5 +/- 37.0 min.wk in MBSR (between-group difference: P = 0.08; d = 0.86),
      whereas it increased by 5.7 +/- 64.1 min.wk in AET (compared with control: P =
      0.029; d = 0.97; compared with MBSR; P = 0.564; d = 0.29). CONCLUSION: Data from
      participants in a randomized controlled trial showed that although AET increases
      MVPA bouts compared with no treatment, MBSR training may also mitigate the
      influence of shorter day length and cooler weather on participation in physical
      activities. Future research is needed to determine how MBSR affects exercise to
      inform interventions. Interventions combining MBSR and exercise may be
      particularly successful at increasing physical activity participation.

PMID- 30113543
TI  - Effectiveness of non-pharmacological interventions for pain and physical function
      in adults with rib fractures: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVES: The review question is: what are the effects of non
      pharmacological therapeutic interventions on pain and physical function in adults
      with rib fractures?The objectives of this systematic review are to determine.

PMID- 30113542
TI  - The economic cost of robotic rehabilitation for adult stroke patients: a
      systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify the best
      available evidence on the economic cost of robotic rehabilitation for adult
      stroke patients to improve their motor movement abilities. More specifically, the
      objective is to identify the evidence on the economic cost of robotic training
      compared to conventional physiotherapy for adult stroke patients, from the
      perspective of hospitals.

PMID- 30113544
TI  - Home oxygen therapy criteria, guidelines and protocols for hypoxia management in
      pediatric patients with acute bronchiolitis: a scoping review protocol.
AB  - REVIEW OBJECTIVE/QUESTION: The objectives of this scoping review are: to explore
      existing literature related to discharge criteria, guidelines and protocols from
      hospitals or clinics that are being implemented for home oxygen therapy (HOT) in
      the management of hypoxia in pediatric patients with acute bronchiolitis, examine
      and conceptually map the evidence, and identify any gaps in the literature.The
      question of this review is: what discharge criteria, guidelines, and protocols
      are used for HOT in the management of hypoxia in pediatric patients with acute
      bronchiolitis?

PMID- 30113545
TI  - Prevalence of mental disorders in Uganda: a systematic review protocol.
AB  - REVIEW QUESTION: The questions to be addressed by this systematic review are.

PMID- 30113546
TI  - Laterality judgment performance between people with chronic pain and pain-free
      individuals: a systematic review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to establish the
      association between chronic pain and laterality judgment. Specifically, the
      review question: Is there a difference in laterality judgment in people with
      chronic pain and pain-free individuals?

PMID- 30113547
TI  - Management of full thickness rotator cuff tears in the elderly: a systematic
      review protocol.
AB  - REVIEW QUESTION/OBJECTIVE: The objective of this review is to synthesize the best
      available evidence on the effectiveness of non-surgical and surgical treatment on
      the clinical and functional outcomes of elderly patients with full thickness
      rotator cuff tear.

PMID- 30113548
TI  - Adherence to activity monitoring devices or smartphone applications for improving
      physical activity in adults with cardiovascular disease: a systematic review
      protocol.
AB  - REVIEW QUESTION: The question of this review is: what is the adherence to the use
      of activity monitoring devices or applications to improve physical activity in
      adults with cardiovascular disease?Specifically, the review objectives are.

PMID- 30113549
TI  - The association between prenatal exposure to environmental tobacco smoke and
      childhood obesity: a systematic review.
AB  - OBJECTIVE: The objective of the review was to determine if prenatal exposure to
      environmental tobacco smoke (ETS) increases the risk of obesity and overweight in
      children. INTRODUCTION: Childhood obesity has reached epidemic proportions in
      many developed countries. This is of great concern as childhood obesity is
      associated with early onset of chronic diseases such as coronary artery disease,
      type II diabetes and hypertension in adulthood. Extensive research suggests a
      multifactorial etiology. These factors include genetic markers, individual
      lifestyle, social and environmental factors, particularly the interaction between
      these factors. Among environmental factors, prenatal exposure to ETS has been
      linked to increased rates of obesity and overweight in childhood. INCLUSION
      CRITERIA: This review considered studies on children of women who were non
      smokers and who reported exposure to ETS during pregnancy. The exposure of
      interest was exposure to ETS or second hand smoke during pregnancy, determined by
      either: i) self-reported maternal exposure; and/or ii) serum cotinine levels.
      Observational studies such as cohort studies, case control studies, retrospective
      studies and analytical cross-sectional studies were included. Outcomes of
      interest were weight, height and body mass index of children from birth up to 18
      years. METHODS: A three-step search strategy was used to search for published and
      unpublished studies in the English language. No search range (years) was set. Two
      reviewers assessed the studies for inclusion and methodological quality using the
      Joanna Briggs Institute System for the Unified Management, Assessment and Review
      of Information (JBI SUMARI) standardized appraisal instruments. Data was
      extracted by two people independently and entered into the JBI extraction tool.
      Extracted data was pooled in a statistical meta-analysis based on a random
      effects model. RESULTS: Nineteen studies were included in the review. Eight of
      the studies were included in the final meta-analysis. Findings suggest that there
      was an association between prenatal exposure to ETS and childhood obesity (odds
      ratio [OR]: 1.905, CI: 1.23-2.94), and no association between ETS exposure and
      overweight (OR: 1.51, CI: 0.49-4.59). The high rates of heterogeneity between
      studies in both of the meta-analyses determined by the I statistic (97% and 99%,
      respectively) sanction caution in the interpretation and use of these findings.
      CONCLUSIONS: Based on the evidence, childhood obesity is associated with exposure
      to prenatal ETS, however overweight does not appear to be associated with this
      type of exposure.

PMID- 30113550
TI  - Effectiveness of multisensory stimulation in managing neuropsychiatric symptoms
      in older adults with major neurocognitive disorder: a systematic review.
AB  - OBJECTIVE: The objective of the review was to synthesize the effectiveness of
      multisensory stimulation in managing neuropsychiatric symptoms (NPS) in older
      adults with major neurocognitive disorder (NCD). INTRODUCTION: Major
      neurocognitive disorder is characterized by changes in specific cognitive domains
      with a progressive deterioration in cognitive ability and capacity for
      independent living. Most older adults with this condition have one or more
      concomitant symptoms known as NPS. Evidence shows that nonpharmacological
      therapies have been effective in controlling these symptoms, with multisensory
      stimulation attracting further investigation. INCLUSION CRITERIA: The review
      considered studies on older adults aged 65 years or over with major NCD. The
      intervention of interest was multisensory stimulation, and the comparator was
      usual care (e.g. no occupational therapy, no cognitive training, and no art
      therapy, but with possible control of activities such as looking at photographs
      or doing quizzes), or another intervention (e.g. occupational therapy, cognitive
      training and art therapy). Primary outcomes were NPS (agitation, aggression,
      motor disturbances, mood liability, anxiety, apathy, night-time behaviour, eating
      disorders, delusion and hallucination). Secondary outcomes were quality of life,
      functional status in activities of daily living, cognitive status and caregiver
      burden. Experimental study designs were considered. METHODS: A broad range of
      keywords and a three-step search strategy were used to identify potentially
      eligible published and unpublished studies from January 1990 to June 2016 in
      major healthcare-related online databases. Studies in English, Spanish and
      Portuguese were included. Two independent reviewers assessed the methodological
      quality of eight included studies using the Joanna Briggs Institute (JBI)
      Critical Appraisal Checklists for Randomized Controlled Trials and Quasi
      Experimental Studies. Data were extracted using the standardized data extraction
      tool from the JBI System for the Unified Management, Assessment and Review of
      Information (JBI SUMARI) and included details about the interventions,
      populations, study methods and outcomes of interest. Significant differences were
      found between participants, interventions, outcome measures (clinical
      heterogeneity), and designs (methodological heterogeneity). For these reasons, a
      meta-analysis could not be performed. Therefore, the results have been described
      in a narrative format. RESULTS: Eight studies (seven randomized controlled trials
      and one quasi-experimental study) were included, with a total sample of 238
      participants (pre-intervention). Four studies confirmed the effectiveness of
      multisensory stimulation in domains such as physically nonaggressive behavior,
      verbally agitated behavior and agitation. However, these effects did not always
      persist in the long-term. Six studies showed poorly consistent results on the
      effects of multisensory stimulation in improving mood, with only one displaying
      significant effects. Similarly, despite poor results, two studies showed benefits
      concerning anxiety. Participants reported significantly decreased levels of
      anxiety over the course of the intervention, and this improvement persisted in
      the long-term. In regard to functional status in activities of daily living, two
      studies reported an improvement in the short-term. Moreover, the effectiveness in
      cognitive domains such as memory and attention to surroundings also showed
      inconsistent results across the seven studies that analyzed this outcome. Two
      studies reflected an improvement during the intervention, but also reported a
      gradual decline in the long-term. Only one study observed significantly better
      results during the intervention that persisted until the follow-up assessment.
      Apathy, night-time behavior, eating disorders, delusion and hallucination were
      NPS that were not explored in the studies that met the criteria to be included in
      this review. CONCLUSIONS: These findings suggest that multisensory stimulation
      could be an effective intervention for managing NPS in older adults with major
      NCD in a mild to severe stage, particularly for managing behavioral symptoms such
      as agitation. This research provides an indication of the likely effect of the
      multisensory stimulation on NPS such as agitation and anxiety, as well on
      cognitive status.

PMID- 30113551
TI  - Improving the accuracy of fluid intake charting through patient involvement in an
      adult surgical ward: a best practice implementation project.
AB  - OBJECTIVES: The main objective of this evidence-based utilization project was to
      improve the accuracy of fluid intake charting through patient involvement.
      INTRODUCTION: The accurate documentation and maintenance of fluid balance charts
      constitute an integral part of nursing care. However, inaccuracies in fluid
      balance charting by nurses often occur. Inaccurate charting can result in delayed
      interventions, affecting the safety of patients. It has been found that fluid
      intake charting in an acute surgical inpatient ward is highly inaccurate. Many
      expressions of dissatisfaction are evident among medical healthcare professionals
      and patients regarding the accurate updating of the charts. Therefore, evidence
      based measures need to be implemented in order to improve the safety of patient
      care through accurate recording of patients' fluid intake. METHODS: The project
      took place in a 21-bed acute surgical ward which had 30 patients. The Joanna
      Briggs Institute Practical Application of Clinical Evidence System (JBI-PACES)
      and Getting Research into Practice (GRiP) tools were used to implement the
      evidence-based project. A pre- and post- audit methodology congruent with the
      framework was applied. The project was implemented in three phases from April to
      September 2016. The audit criteria obtained from JBI-PACES were used. The
      project's primary focus was to harness patient involvement in improving the
      accuracy of fluid intake charting. RESULTS: Criteria 1 and 2 revealed low levels
      of compliance during the pre-implementation audit, 3% and 10%, respectively.
      There were significant improvements one month post-implementation for both
      Criteria 1 and 2, 100% and 87%, also respectively. Fisher's exact test was
      carried out and the statistical significance of the results was achieved (p <
      0.001), compared to the pre-implementation audit. At six months post
      implementation, the audit found that both criteria were adequately sustained as a
      practice in the ward (Criterion 1: 100%, Criterion 2: 83%). CONCLUSIONS: This
      project has demonstrated the effectiveness of improving the accuracy of fluid
      intake charting through patient involvement. The use of JBI-PACES and GRiP has
      allowed the effective utilization of evidence in practice. It has also provided
      evidence that effective engagement of the ground nurses and stakeholders coupled
      with the commitment of change champions and ground nurses can contribute to
      improving practice in a highly demanding acute care setting and lead to
      healthcare success.

PMID- 30113552
TI  - Falls prevention strategies for adult inpatients in a university hospital of Sao
      Paulo, Brazil: a best practice implementation project.
AB  - OBJECTIVES: The main objective of this project was to reduce the incidence and
      harm from falls that occur among patients admitted in the acute Internal Medicine
      Unit and Intensive Care Unit in a public teaching hospital in Sao Paulo, Brazil.
      INTRODUCTION: Falls are a challenge for health professionals and healthcare
      services as they may result in high-impact outcomes for patients, such as
      functional decline, increase in length of hospital stay, increase in the cost of
      healthcare services, and death. In an attempt to promote safe care the World
      Health Organization (WHO) launched the World Alliance for Patient Safety in 2004
      that encourages the adoption of best practice to reduce adverse events in
      healthcare services. METHODS: The project used the Joanna Briggs Institute
      Practical Application of Clinical Evidence System (JBI-PACES) and Getting
      Research into Practice (GRiP) audit tool for promoting change in health practice.
      A baseline audit was conducted measuring eight best practice criterias, followed
      by the implementation of target strategies and a follow-up audit. RESULTS: The
      results of the baseline audit identified large gaps between current practice and
      overall compliance with best practice. The GRiP module helped identify strategies
      related to education programs for patients, families and nursing teams, and a
      falls risk assessment with an accurate tool to address the gaps in compliance.
      The follow-up audit cycle was satisfactory as all best practice audit criteria
      showed an improvement as an aggregated result. CONCLUSIONS: The project used the
      audit and feedback strategy to translate evidence into practice. Some of the
      measured criteria improved to moderate-high compliance with best practice. The
      results showed that implementation of evidence-based practice leads to an
      improvement in falls prevention. Future audits are required to sustain
      improvements.

PMID- 30113553
TI  - Augmented Reality of the Middle Ear Combining Otoendoscopy and Temporal Bone
      Computed Tomography.
AB  - HYPOTHESIS: Augmented reality (AR) may enhance otologic procedures by providing
      sub-millimetric accuracy and allowing the unification of information in a single
      screen. BACKGROUND: Several issues related to otologic procedures can be
      addressed through an AR system by providing sub-millimetric precision, supplying
      a global view of the middle ear cleft, and advantageously unifying the
      information in a single screen. The AR system is obtained by combining
      otoendoscopy with temporal bone computer tomography (CT). METHODS: Four human
      temporal bone specimens were explored by high-resolution CT-scan and dynamic
      otoendoscopy with video recordings. The initialization of the system consisted of
      a semi-automatic registration between the otoendoscopic video and the 3D CT-scan
      reconstruction of the middle ear. Endoscope movements were estimated by several
      computer vision techniques (feature detectors/descriptors and optical flow) and
      used to warp the CT-scan to keep the correspondence with the otoendoscopic video.
      RESULTS: The system maintained synchronization between the CT-scan image and the
      otoendoscopic video in all experiments during slow and rapid (5-10 mm/s)
      endoscope movements. Among tested algorithms, two feature-based methods, scale
      invariant feature transform (SIFT); and speeded up robust features (SURF),
      provided sub-millimeter mean tracking errors (0.38 +/- 0.53 mm and 0.20 +/- 0.16
      mm, respectively) and an adequate image refresh rate (11 and 17 frames per
      second, respectively) after 2 minutes of procedure with continuous endoscope
      movements. CONCLUSION: A precise augmented reality combining video and 3D CT-scan
      data can be applied to otoendoscopy without the use of conventional
      neuronavigation tracking thanks to computer vision algorithms.

PMID- 30113554
TI  - Preliminary Study on Antinuclear Antibodies in Patients With Chronic Dilatory
      Eustachian Tube Dysfunction.
AB  - BACKGROUND AND HYPOTHESIS: There are some known reasons for chronic dilatory
      Eustachian tube dysfunction (chronic D-ETD, also known as chronic obstructive
      tube dysfunction), for example infections, hyperplastic adenoids, or tumors. In
      many cases though, none of these reasons apply. The question arises whether there
      might be an autoimmune pathogenesis in patients with idiopathic chronic D-ETD.
      METHODS: The study includes 31 consecutive patients with chronic D-ETD and 92
      consecutive blood donors (BD, comparative cohort). The production of antinuclear
      antibodies (ANA), as an indicator for autoimmune pathologies, was measured in the
      serum of patients and BD. RESULTS: ANA titers were significantly higher in
      patients with chronic D-ETD, compared with BD (p = 0.0027). The results weighted
      clearly toward higher ANA titers in younger patients. A comparison of ANA titers
      in patients and BD aged less than 40 years showed a significant difference (p =
      0.0062), whereas it was not significant between patients and BD aged >= 40 years
      (p = 0.19). CONCLUSION: The significant results of elevated ANA titers in chronic
      D-ETD make an autoimmune pathogenesis highly probable, at least in some of the
      patients concerned. Further research with higher numbers of patients is needed to
      confirm the hypothesis of an autoimmune chronic D-ETD. A better understanding of
      etiology and pathogenesis of chronic D-ETD might open up new and perhaps even
      causal therapeutic strategies.

PMID- 30113555
TI  - Further Beneficial Effect of Hearing Aids on Speech Recognition Performance
      Besides Amplification: Importance of the Restoration of Symmetric Hearing.
AB  - OBJECTIVE: To identify the improvement in auditory spectral resolution, temporal
      resolution, and speech recognition conferred with various hearing-aid (HA)
      technologies when the amplification effect of the HA is excluded, and to compare
      the beneficial effects depending on the restoration of symmetric hearing with
      different amplification settings in various hearing impairment conditions. STUDY
      DESIGN: Prospective study. SETTING: Tertiary referral center. SUBJECTS: Sixty-two
      subjects who had used HAs for more than 3 months were divided into four groups:
      group 1, bilateral HAs (n = 28); group 2, unilateral HA in the better ear (n =
      12); group 3, unilateral HA in the worse ear (n = 12); group 4, unilateral HA
      with symmetric hearing thresholds (n = 10). METHODS: Aided performance and
      unaided performance were compared in each group. Four different psychoacoustic
      measurements were made: 1) spectral ripple discrimination; 2) temporal modulation
      detection; 3) speech recognition threshold in white noise; and 4) speech
      discrimination score (SDS) under quiet conditions. All test signals were
      presented by a loudspeaker located 1 m in front of the subject in a sound
      attenuating booth, at their most comfortable levels, with or without HAs.
      RESULTS: In group 1, the use of HAs significantly improved both SDS under quiet
      conditions and speech recognition in noise compared with the unaided condition.
      Group 2 showed better SDS under quiet conditions with HAs, and group 3 showed
      improved speech recognition in noise with HAs. In contrast, in group 4, no
      measurements differed with or without HAs. CONCLUSIONS: These results demonstrate
      the benefits of HAs on speech perception in noise, in addition to their
      amplification effect, but only when HA restores symmetric hearing.

PMID- 30113556
TI  - Hearing Loss Asymmetry due to Chronic Occupational Noise Exposure.
AB  - OBJECTIVE: To determine whether occupational noise exposure causes symmetrical or
      asymmetrical hearing loss. STUDY DESIGN: Retrospective Case Series. SETTING:
      Otorhinolaryngology Specialist Centre. PATIENTS: Seven hundred forty-four reports
      for occupational noise-induced hearing loss (NIHL) compensation were analyzed.
      Subjects with at least 40% of their total hearing loss due to occupational NIHL
      were included. Claimants with any confounding factor that could cause asymmetric
      hearing loss such as history of shooting, head, or ear trauma were excluded. With
      the strict inclusion criteria, 83 subjects were included in the study. Claimants
      with >=40%, >=60%, and >=80% occupational NIHL of their total hearing loss were
      compared. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The left ear hearing
      threshold compared with the right ear hearing threshold (dB) at the frequencies
      0.5 to 8 kHz. RESULTS: In the total group, the left ear hearing threshold was
      statistically significantly higher compared with the right ear at 3 kHz (2.41
      dB). In the subgroups >=60% and >=80% occupational NIHL of total hearing loss,
      the left ear hearing threshold was statistically significant higher compared with
      the right ear at 3 kHz, respectively, 3.81 dB and 5.53 dB and 4 kHz,
      respectively, 2.86 dB and 5.53 dB. An asymmetry of more than 10 dB at 3 and 4 kHz
      was observed in 39% and 30% of the subjects respectively. In these cases, the
      vast majority had more pronounced hearing loss in the left ear. CONCLUSION:
      Findings of this study further indicate that the left ear is more susceptible to
      noise exposure compared with the right ear.

PMID- 30113558
TI  - Evolving Trends in Cochlear Implantation: A Critical Look at the Older
      Population.
AB  - OBJECTIVES/HYPOTHESIS: Cochlear implantation (CI) is a well-accepted surgical
      option for the treatment of moderate to profound deafness. The purpose of this
      study was to evaluate the temporal and geographic trends of this procedure
      nationwide in the Medicare population in an attempt to explore the impact of
      evolving technologies and changes in healthcare policy. METHODS: Medicare Part B
      national summary procedural datasets from 2007 to 2016 were obtained. Current
      Procedural Terminology codes for CI as well as auditory osseointegrated
      implantation were obtained. Centers for Medicare and Medicaid Services (CMS)
      datasets were evaluated to determine temporal trends. For geographic trends,
      specific carrier datasets from 2007 and 2016 were used. RESULTS: From 2007
      through 2016, the number of CI procedures increased annually from 1603 to 3600
      (124.6%). Other procedures to treat hearing loss including bone-anchored
      implantation exhibited comparatively modest increases (23%, 90%). CI procedures
      increased every year in contrast to bone-anchored implants. Controlling for
      Medicare population, the greatest number of CI procedures performed per capita in
      the United States was in the West North Central, with an average 1.05 CIs per
      10,000 beneficiaries. CONCLUSION: The number of CI procedures performed in the
      elderly population has increased markedly over the past 10 years, far outpacing
      growth in other hearing surgeries. Potential reasons may relate to changes in
      criteria for CI candidacy over the past decade, although significant regional
      variability demonstrated suggests a lack of consensus. Further studies would be
      necessary to ascertain the true reason for geographic disparities.

PMID- 30113557
TI  - Intra-Cochlear Electrocochleography During Cochear Implant Electrode Insertion Is
      Predictive of Final Scalar Location.
AB  - HYPOTHESIS: Electrocochleography (ECochG) patterns observed during cochlear
      implant (CI) electrode insertion may provide information about scalar location of
      the electrode array. BACKGROUND: Conventional CI surgery is performed without
      actively monitoring auditory function and potential damage to intracochlear
      structures. The central hypothesis of this study was that ECochG obtained
      directly through the CI may be used to estimate intracochlear electrode position
      and, ultimately, residual hearing preservation. METHODS: Intracochlear ECochG was
      performed on 32 patients across 3 different implant centers. During electrode
      insertion, a 50-ms tone burst stimulus (500 Hz) was delivered at 110 dB SPL. The
      ECochG response was monitored from the apical-most electrode. The amplitude and
      phase changes of the first harmonic were imported into an algorithm in an attempt
      to predict the intracochlear electrode location (scala tympani [ST],
      translocation from ST to scala vestibuli [SV], or interaction with basilar
      membrane). Anatomic electrode position was verified using postoperative computed
      tomography (CT) with image processing. RESULTS: CT analysis confirmed 25
      electrodes with ST position and 7 electrode arrays translocating from ST into SV.
      The ECochG algorithm correctly estimated electrode position in 26 (82%) of 32
      subjects while 6 (18%) electrodes were wrongly identified as translocated
      (sensitivity = 100%, specificity = 77%, positive predictive value = 54%, and a
      negative predictive value = 100%). Greater hearing loss was observed
      postoperatively in participants with translocated electrode arrays (36 +/- 15 dB)
      when compared with isolated ST insertions (28 +/- 20 dB HL). This result,
      however, was not significant (p = 0.789). CONCLUSION: Intracochlear ECochG may
      provide information about CI electrode location and hearing preservation.

PMID- 30113559
TI  - No Squelch Effect After Sequential Bilateral Cochlear Implantation in
      Postlingually Deafened Adults: Is There a First Ear Advantage?
AB  - OBJECTIVES: To investigate whether a squelch effect develops in postlingually
      deafened adults after sequential bilateral cochlear implantation. STUDY DESIGN:
      Prospective study as part of a randomized controlled trial on the difference
      between simultaneous versus sequential bilateral cochlear implantation. SETTING:
      Tertiary referral center. PARTICIPANTS: Sixteen postlingually deafened adults.
      INTERVENTION: Sequential bilateral cochlear implantation with a 2-year
      interimplant interval. MAIN OUTCOME MEASURE: A squelch effect was defined as a
      better bilateral score than unilateral score on a speech-intelligibility-in-noise
      test with spatially separated sources. The squelch effect was evaluated for the
      participants' best performing cochlear implant (CI) ear, the left CI in the
      condition with speech from -60 degrees azimuth and noise from +60 degrees azimuth
      (S-60 N+60), the right CI (N-60 S+60), CI1 and CI2. Evaluations took place 1, 2
      and median 4 years after sequential implantation. RESULTS: No significant squelch
      effect was found, except for the right CI (N-60 S+60) after 2 years. No
      differences in speech perception-in-noise from straight ahead were seen between
      CI1 and CI2. Comparing performance of participants whose better or worse ear was
      implanted first did not reveal differences either. For the best performing
      situation, 7/16, 6/16, and 3/12 participants exhibited a squelch effect after 1,
      2, and 4 years of follow-up. CONCLUSIONS: Participants who underwent sequential
      bilateral cochlear implantation with a 2-year interimplant interval did not
      develop an evident squelch effect on group level after a median follow-up of 4
      years. Individual participants were able to make use of the squelch effect. The
      less evident squelch effect is at odds with our group of simultaneously implanted
      bilateral cochlear implant users. Neither a difference between CI1 and CI2, nor
      implanting the better or worse ear first could explain the less evident squelch
      effect in these patients. TRIAL REGISTRATION: Dutch Trial Register NTR1722.

PMID- 30113561
TI  - Complications in Endoscopic Ear Surgery.
AB  - OBJECTIVE: The aim of this study was to examine the premise that endoscopic ear
      surgery (EES) is associated with a low rate of complications (intraoperative and
      postoperative). STUDY DESIGN: Retrospective review at two institutions. SETTING:
      Tertiary referral center. PATIENTS: The study included 825 patients who underwent
      exclusive EES between 2008 and 2016 at the Otorhinolaryngology-Head and Neck
      Surgery Department of Modena University Hospital, and between 2014 and 2016 at
      the Otorhinolaryngology-Head and Neck Surgery Department of Verona University
      Hospital. INTERVENTIONS: Exclusive endoscopic ear surgery between 2008 and 2016
      (tympanoplasties, second look or revision tympanoplasties, myringoplasties,
      stapedoplasties, canalplasties, ossiculoplasties, and exploratory tympanotomies).
      All surgical procedures were performed by two experienced surgeons. MAIN OUTCOME
      MEASURE: For each procedure, intraoperative, and early and delayed postoperative
      complications were evaluated. RESULTS: The most common ear pathologies for which
      patients were sent for EES were cholesteatoma (33.6%), chronic otitis media
      (36.3%) and otosclerosis (26.8%). There was no case of major intraoperative
      complications such as injury to the dura or vascular structures. We observed
      minor intraoperative complications in 4.1% of the cases. Only 1.3% of patients
      experienced early postoperative complications. Delayed complications affected
      less than 1% of the cohort. CONCLUSIONS: Data from this study confirm the safety
      of the endoscopic technique, with very low complication rates, indicating that
      EES is a reliable therapeutic option, in particular, for tympanoplasties,
      myringoplasties, and stapedoplasties, as well as second look procedures. We have
      reported our experience with EES morbidity so that it can be compared with data
      from other centers using the same surgical technique.

PMID- 30113562
TI  - Proposal of a Treatment Strategy for Eosinophilic Otitis Media Based on Middle
      Ear Condition.
AB  - OBJECTIVE: We classified eosinophilic otitis media (EOM) into three grades (G1
      G3) based on the middle ear mucosal thickness and aimed to establish a treatment
      strategy for EOM based on these pathological categories. STUDY DESIGN:
      Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: We
      evaluated 136 ears of 68 patients (38 women, 30 men; average age, 56.1 yr; range,
      32-80 yr) with bilateral EOM, including 14 surgically treated ears.
      INTERVENTIONS: Diagnostics and treatment. MAIN OUTCOME MEASURES: Treatment
      responses to intratympanic instillation of triamcinolone acetonide (TA) and
      surgery. RESULTS: G1 (mild) cases of EOM responded well to intratympanic TA. G2
      (moderate) cases required both TA and systemic glucocorticoids. G3 (severe) cases
      with granulation were unresponsive to but tolerated the treatment. In 14 ears,
      granulation tissue was surgically removed and the area was covered with a gelatin
      sponge containing TA. After the surgery, the severity level of EOM decreased from
      G3 to G2 in 12 ears, and hearing improved in 4 ears. Three ears showed
      normalization of the tympanic membrane, and seven ears had less otorrhea. Risk
      factors for granulation (G3) were the presence of bacterial infection (p = 0.017)
      and diabetes mellitus (HbA1c of >=6.5%) (P = 0.039) (odds ratios of 4.55 and
      3.95, respectively). CONCLUSIONS: This study showed that G3 EOM was unresponsive
      to conservative glucocorticoid treatment and required granulation tissue removal.
      Classification based on the middle ear pathology is useful for determining the
      most appropriate and successful treatment for EOM.

PMID- 30113560
TI  - Acute Otitis Media and Associated Complications in United States Emergency
      Departments.
AB  - OBJECTIVE: Complications due to acute otitis media (AOM), while rare, are
      associated with significant morbidity and are not well characterized from an
      epidemiological perspective. We analyze the pattern of presentation and emergency
      department (ED) utilization in patients with AOM and associated complications.
      STUDY DESIGN: Retrospective analysis of the Nationwide Emergency Department
      Sample (NEDS) from 2009 to 2011. SETTING: Emergency Department. PATIENTS:
      Patients who presented with a primary diagnosis of AOM or acute mastoiditis.
      INTERVENTION: Diagnostic. MAIN OUTCOME MEASURES: NEDS was queried for patient
      encounters with a diagnosis of AOM or acute mastoiditis based on ICD-9 codes.
      Complications of severe infection, including petrositis, Gradenigo's syndrome,
      facial paresis, labyrinthitis, meningitis, intracranial abscess, venous sinus
      thrombosis, and cerebrospinal fluid leak, were assessed. Weighted estimates for
      demographics, types of complications, socioeconomic status, and trends over time
      were extracted. RESULTS: A weighted total of 5,811,127 ED visits were identified.
      The majority of patients were less than 18 years old (79.9%) with an average age
      of 10.1 years. Most were discharged (99.4%). There were 15,243 (0.26%) patients
      who presented with a complication. The most common complications were acute
      mastoiditis (0.16%), labyrinthitis (0.06%), and facial paresis (0.03%). Compared
      with patients with uncomplicated AOM, patients with complicated AOM were older
      (37 vs. 10-yr old), insured by Medicare (18% vs. 2.1%), and more likely to be
      admitted (43.6% vs. 0.4%) (p < 0.0001, for all comparisons). CONCLUSIONS: ED
      visits related to AOM or mastoiditis are common and complications are rare. An in
      depth analysis on a national level is useful for assessing healthcare utilization
      trends.

PMID- 30113563
TI  - Evolution of Acquired Middle Ear Cholesteatoma in Patients With Ectrodactyly,
      Ectodermal Dysplasia, Cleft Lip/Palate (EEC) Syndrome.
AB  - OBJECTIVE: To review an institutional experience with the surgical and clinical
      management of acquired middle ear cholesteatoma in patients with ectrodactyly,
      ectodermal dysplasia, cleft lip/palate (EEC) syndrome. STUDY DESIGN:
      Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Eight
      patients with medical history significant for EEC syndrome who underwent surgery
      for acquired middle ear cholesteatoma between 1996 and 2016. INTERVENTION(S):
      Appropriate surgical interventions at the time of admission. MAIN OUTCOME
      MEASURE(S): History of ventilation tube insertion, status of the contralateral
      ear, surgical technique, cholesteatoma recidivism, presence of postoperative
      external auditory canal stenosis, pre and postoperative audiograms. RESULTS:
      Cholesteatoma was diagnosed in all patients, 3 (37.5%) unilateral and 5 (62.5%)
      bilateral, totalizing 13 ears. Six ears (46.2%) underwent a canal wall up
      mastoidectomy but required conversion to a canal wall down technique in a second
      procedure due to recurrent cholesteatoma. In the remaining seven ears (53.8%) a
      canal wall down mastoidectomy was performed. Of all meatoplasty performed, seven
      (53.8%) evolved with stenosis of the external auditory canal. CONCLUSIONS: Our
      results suggest that most patients with EEC syndrome and middle ear cholesteatoma
      should be considered for a canal wall down mastoidectomy due to extensive disease
      and a high rate of recidivism. In addition, a high percentage of postoperative
      stenosis of the external auditory canal was found in this group.

PMID- 30113564
TI  - Reducing Radiation Dose for High-resolution Flat-panel CT Imaging of Superior
      Semicircular Canal Dehiscence.
AB  - OBJECTIVE: High-resolution flat panel computed tomography (FPCT) is useful for
      the evaluation of temporal bone pathologies. While radiation exposure remains a
      concern, efforts have been devoted to reduce dose, while maintaining image
      quality. We hypothesize that removing the antiscatter grid (ASG) results in
      decreased radiation exposure, while maintaining diagnostic image quality for the
      evaluation of superior semicircular canal dehiscence (SSCD). METHODS: Ten
      patients with clinical suspicion for SSCD participated in this prospective study.
      Two sequential collimated 20-second FPCT acquisitions were performed (first: grid
      in; second: grid removed) in all patients. Secondary reconstructions were created
      by manually generating the volume of interest to include the middle ear using a
      voxel size of 0.1 mm and 512 * 512 matrix. Radiation dose parameters (air kerma
      (Ka,r) in mGy and dose area product (DAP) in MUGym) were recorded. Three
      reviewers analyzed images for the ability to diagnose SSCD, to identify the
      stapes crurae, and to determine if an ASG was present. RESULTS: The average Ka,r
      and DAP for the grid-in acquisitions were 246.7 mGy (SD 47.9) and 2838.0 MUGym
      (SD 862.8), versus 160.2 mGy (SD 33.2) and 2026.3 MUGym (SD 644.8) for the grid
      out acquisitions, respectively (p<0.001 for both Ka,r and DAP). Radiation
      exposure was reduced by approximately 30% solely by removing the ASG. All
      reviewers correctly identified all patients with SSCD (confirmed at surgery),
      with mean AUC of 0.99 (kappa = 0.90). CONCLUSION: Removing the antiscatter grid
      during FPCT imaging of the temporal bones is a simple and effective way to reduce
      radiation exposure while maintaining diagnostic image quality for the evaluation
      of SSCD.

PMID- 30113565
TI  - The SLC26A4 c.706C>G (p.Leu236Val) Variant is a Frequent Cause of Hearing
      Impairment in Filipino Cochlear Implantees.
AB  - HYPOTHESIS: Variants in SLC26A4 are an important cause of congenital hearing
      impairment in the Philippines. BACKGROUND: Cochlear implantation is a standard
      rehabilitation option for congenital hearing impairment worldwide, but places a
      huge cost burden in lower-income countries. The study of risk factors such as
      genetic variants that may help determine genetic etiology of hearing loss and
      also predict cochlear implant outcomes is therefore beneficial. METHODS: DNA
      samples from 29 GJB2-negative Filipino cochlear implantees were Sanger-sequenced
      for the coding exons of SLC26A4. Exome sequencing was performed to confirm
      results. RESULTS: Four cochlear implantees with bilaterally enlarged vestibular
      aqueducts (EVA) were homozygous for the pathogenic SLC26A4 c.706C>G (p.Leu236Val)
      variant, which has a minor allele frequency of 0.0015 in Filipino controls. In
      patients with the SLC26A4 variant there was no association between cochlear
      implant outcome and age at implantation or duration of implant. There was also no
      association between the occurrence of the SLC26A4 variant and postsurgical
      audiometric thresholds and parents' evaluation of aural/oral performance of
      children (PEACH) scores. On the other hand, the SLC26A4 variant increased
      presurgical median audiometric thresholds (p = 0.01), particularly at 500 to 2000
      Hz. CONCLUSION: The SLC26A4 c.706C>G (p.Leu236Val) variant is a frequent cause of
      congenital hearing impairment in Filipinos and is associated with bilateral EVA
      and increased presurgical audiometric thresholds, but does not adversely affect
      post-implant outcomes.

PMID- 30113567
TI  - Novel Computed Tomography Findings Suggestive of Perilymph Gusher.
AB  - OBJECTIVES: Perilymphatic gusher (PLG) is an uncommon complication of
      stapedectomy and cochlear implant placement. Computerized tomography (CT) may
      reveal congenital dysplasia responsible for PLG but may also be (incorrectly)
      interpreted as normal. The aim of this study was to review CT findings in
      patients with PLG reported to have normal temporal bones. PATIENTS: Patients in
      which a PLG was encountered and preoperative CT imaging had been interpreted as
      normal. INTERVENTION: Collaborative review of temporal bone computed tomography
      by neurotologist and neuroradiologist. MAIN OUTCOME MEASURE: Identification of
      undetected inner ear anomalies that may predispose to PLG. RESULTS: Unanticipated
      PLG was encountered during stapes surgery in two patients and cochlear
      implantation in one. A focal bony dehiscence between the basal turn of the
      cochlea and internal auditory canal (IAC) was identified on a few oblique
      reformatted images in all patients. CONCLUSIONS: High resolution CT with oblique
      image reformatting is essential to identify focal communication between the IAC
      and basal turn of the cochlea in ears with PLG.

PMID- 30113566
TI  - Prevention of Chlorhexidine Ototoxicity With Poloxamer in Rats.
AB  - OBJECTIVE: Skin preparations, like chlorhexidine, are toxic to the inner ear,
      preventing their use as a preoperative skin disinfectant in the presence of a
      nonintact eardrum (e.g., perforation or tube). We aimed to determine if a
      poloxamer gel applied over perforated eardrums could prevent chlorhexidine
      ototoxicity. STUDY DESIGN: Controlled, in vivo. SETTING: Academic research
      laboratory. SUBJECTS AND METHODS: Bilateral myringotomies were performed on 20
      Sprague-Dawley rats. Half had poloxamer placed over both eardrums before
      treatment. All rats had chlorhexidine instilled in one ear and saline in the
      other. Auditory brainstem response thresholds were measured before and 2- and 4
      weeks posttreatment. Cochlear hair cell damage was assessed using scanning
      electron microscopy. RESULTS: Ears with chlorhexidine without poloxamer had
      significant hearing loss, 37 to 50 dB worse than the other three ear treatments
      at 2 and 4 weeks posttreatment, at all tested frequencies (4, 18, 16, and 24 kHz;
      all p < 0.0001). No significant hearing loss was observed in ears that were
      treated with poloxamer and chlorhexidine (-2 to 8 dB) and the results were not
      different from the ears that received saline, with or without poloxamer (-2.5 to
      8 dB and 5-17 dB; p > 0.05). Electron microscopy showed far more outer hair cell
      damage in the no poloxamer + chlorhexidine ears compared with the other three
      treatments. CONCLUSION: The use of a poloxamer barrier may be an effective
      approach to prevent ototoxicity before chlorhexidine disinfection of the ear with
      a nonintact tympanic membrane.

PMID- 30113568
TI  - Functional status with rhythm- versus rate-control strategy for persistent atrial
      fibrillation.
AB  - Introduction Recent studies have shown that rhythm control does not provide
      additional benefit over rate control in terms of morbidity or mortality and is
      less cost effective in patients with atrial fibrillation (AF). It remains to be
      determined if any of the treatment strategies should be favored on the basis of
      the quality of life (QoL) or functional capacity. Objectives This HOT CAFE
      substudy was conducted to compare the functional status of patients with
      persistent AF assigned either to rate or rhythm control strategy. Patients and
      methods We enrolled 205 patients (mean [SD] age, 60.8 [11.2] years) with
      persistent AF who were randomly assigned either to rate or rhythm control
      strategies. The New York Heart Association (NYHA) functional classification,
      intensity of arrhythmia-related symptoms, exercise tolerance, and QoL were
      analyzed. Results After a mean (SD) of 1.7 (0.4) years, the NYHA class and QoL
      improved in both groups. Both strategies lead to improvement in AF-related
      symptoms. Treadmill test duration and maximal workload increased over time in
      both groups. In terms of NYHA class improvement, rhythm control was superior to
      rate control in patients with AF and hypertension (odds ratio [OR], 1.89; 95% CI,
      0.98-3.65; P = 0.055) and in those with moderate HF (OR, 2.04; 95% CI, 1.03-4.06;
      P = 0.04). When success was considered as left ventricular function improvement,
      the rhythm-control strategy also proved to be superior in patients with
      hypertension (OR, 2.64; 95% CI, 1.21-5.74; P = 0.01) and those with NYHA class II
      or III (OR, 4.27; 95% CI, 1.25-9.85; P <0.001). Conclusions Rate- and rhythm
      control strategies improved functional status in patients with persistent AF.
      However, rhythm control might be more appropriate for patients with AF and
      hypertension and those with moderate HF.

PMID- 30113569
TI  - Does vitamin C prevent the common cold?
AB  - INTRODUCTION: The common cold is one of the most common diseases. It is generally
      believed that the consumption of vitamin C prevents its appearance, but the
      actual efficacy of this measure is controversial. METHODS: To answer this
      question we used Epistemonikos, the largest database of systematic reviews in
      health, which is maintained by screening multiple information sources, including
      MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic
      reviews, reanalyzed data of primary studies, conducted a meta-analysis and
      generated a summary of findings table using the GRADE approach. RESULTS AND
      CONCLUSIONS: We identified eight systematic reviews including 45 studies overall,
      of which 31 were randomized trials. We concluded the consumption of vitamin C
      does not prevent the incidence of common cold.

PMID- 30113570
TI  - Challenges facing the Cuban State arising from demographic aging.
AB  - Demographic aging in Cuba, which has been occurring for over two decades, is
      undoubtedly an achievement of the country?s public health policies and social
      development. Although the State instituted a system of care aimed at guaranteeing
      elderly people favorable conditions for aging, the social achievement of greater
      longevity creates new challenges for social policy, infrastructure, healthcare
      systems and social inclusion. The Cuban population is diminishing and at the same
      time, life expectancy is increasing. These two conditions increase the proportion
      of people aged 60 and over, thus introducing a new scenario of an aging
      population. The present article analyzes some of the challenges that the Cuban
      State must face when developing policies that address and preserve the social
      achievement of a greater longevity, together with the conditions inherent in the
      development model that the country endorses.

PMID- 30113571
TI  - Are postoperative prophylactic antibiotics effective for orbital fracture?
AB  - INTRODUCTION: Infection is one of the main complications of orbital fracture,
      either because of the connection to the paranasal sinuses or as a postoperative
      complication. Despite the advances made in this condition, there is still
      controversy regarding the role of prophylactic antibiotics. METHODS: To answer
      this question we used Epistemonikos, the largest database of systematic reviews
      in health, which is maintained by screening multiple information sources,
      including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the
      systematic reviews, reanalyzed data of primary studies and generated a summary of
      findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified
      only one systematic review including four studies overall, of which only one was
      a randomized trial. We concluded that postoperative antibiotic prophylaxis might
      not decrease the risk of infection in orbital fracture, and probably increases
      the risk of diarrhea.

PMID- 30113572
TI  - [Global action for hearing loss].
AB  - Over 6% of the world's population lives with disabling hearing loss which can
      adversely affect their development, education and overall health. Unless action
      is taken, it is expected that by 2050 the prevalence of hearing loss could grow
      to nearly 10%. Many of the causes responsible for this growth, such as noise,
      ototoxicity and ear infections are preventable through public health measures. In
      those who develop hearing loss: appropriate, timely and cost effective
      interventions can reduce its adverse impact. However, most people do not have
      access to the required ear and hearing care services. Strong government-led
      action, is required to address this issue. Such action must focus on raising
      awareness in all sections of society and providing services to address hearing
      loss. Professional groups and civil society has to support governments in
      developing and implementing evidence-based policies that can ensure accessible
      ear and hearing care for all.

PMID- 30113573
TI  - [The electrically evoked potentials of the auditory cortex].
AB  - The problems concerning the registration of late latency auditory responses to
      electric stimulation in the patients wearing cochlear implants are considered.
      The renewed interest to this class of evoked potentials is due to unexplained
      differences in the results of cochlear implantation in the patients with the
      similar audiological data, etiology, age and the history of deafness as well as
      cochlear implant surgery in children of first years of life and the extended
      possibilities for speech processor programming. It is maintained that the
      advantages of this method include the possibility to objectively evaluate the
      ability of brain to detect and discriminate between different stimulus
      characteristics, such as loudness differences, temporal changes or speech tokens.
      This method is of great clinical significance for the electrophysiological
      monitoring of brain plasticity and documentation of the clinical effectiveness of
      different rehabilitation methods. Based on our own experimental and clinical
      results and the literature data, we consider the application of different
      electrically evoked late latency potentials for the monitoring of the auditory
      pathway maturation dynamics during the electric stimulation as well for the
      estimation of the effectiveness of cochlear implantation. It is concluded that
      the longer duration of deafness and later age at implantation result in immature
      morphology and delayed peak latencies and that patients with shorter latencies
      and higher amplitudes have better speech perception. The use of different classes
      of electrically evoked responses of auditory cortex could provide the objective
      control of the effectiveness of the rehabilitative measured in the children
      following cochlear implantation.

PMID- 30113574
TI  - [Auditory evoked potentials in children with auditory neuropathy spectrum
      disorder].
AB  - The objective of the present study was to estimate peculiarities of the auditory
      brainstem evoked potentials (ABR), auditory steady-state responses (ASSR) and
      cortical auditory evoked potentials (CAEP) in the children presenting with
      bilateral auditory neuropathy spectrum disorder (ANSD). The study included 100
      patients with bilateral ANSD diagnosed based on the positive response of
      otoacoustic emissions (OAEs) and/or cochlear microphonic (CM) detection, while no
      synchronous neural activity was detected in the ABR test. Cochlear microphonic
      was the main clue for the ANSD diagnosing, because OAE was absent in both ears of
      49 children. ABR testing revealed no response bilaterally in 72 cases (out of
      100). In contrast to ABR, the ASSR thresholds were detectable at all the four
      main frequencies in both ears in 73 % of the cases (47 out of the 64 tested
      ones). Both ABR and ASSR in most cases were incomparable with the behavioral
      audiometric thresholds. 28 children underwent CAEP testing. In 7 cases out of 8
      with mild hearing loss detectable CAEP were recorded. CAEP registration in l7
      children making use of the hearing aids and in 3 children after cochlear
      implantation revealed, in the majority of the cases, the concordance between CAEP
      detectability with behavioral thresholds and rehabilitation outcomes with fairly
      good speech intelligibility. It is concluded that the ABR registration with CM
      evaluation is the most informative test for ANSD diagnosis. However, ABR as well
      as ASSR is useless for the estimation of the behavioral thresholds. The results
      of this study suggest that the presence or absence of CAEPs can provide some
      indication of the audibility of a speech sound in the children with ANSD; however
      this method requires further investigation.

PMID- 30113575
TI  - [Evoked potentials in the rehabilitation of the patients after cochlear
      implantation].
AB  - The objective methods for the hearing examination of the patients after cochlear
      implantation provide an important tool for the speech processor fitting. The aim
      of the present study was to evaluate the possibilities and the informative value
      of the electrically evoked compound action potential (ECAP) and electrically
      evoked auditory brainstem response (EABR) combined recording technique. For this
      reason, the comparison of the ECAP and EABR thresholds with comfortable levels of
      stimulation, obtained on the basis of subjective response and psychophysical
      testing of the patients with good results after cochlear implantation was
      performed. 19 patients with the CI experience from 1 to 5 years were included in
      our study. The combined registration of ECAP and EABR can be used to evaluate the
      functional capacity of the central auditory pathways and for the fitting of the
      complicated patients, especially those in whom the registration proved impossible
      with the use of other objective techniques. The ECAP and EABR threshold values
      were well correlated with the individual stimulation map profiles in the patients
      with the CI experience of less than two years (p<0.05). The results obtained in
      the present study allow us to conclude that combined registration of ECAP and
      EABR could be used for the determination of stimulation comfort level parameters
      and individual stimulation map profiles, especially in combination with the
      minimum amount of psychoacoustic information received from the patient.

PMID- 30113576
TI  - [The method for the simultaneous registration of several frequency-specific short
      latency auditory brain-stem responses].
AB  - The present article was designed to describe the newly proposed method for the
      simultaneous registration of several frequency-specific short latency auditory
      evoked potentials based on the use of the sequences of the maximum length. The
      mutual masking between he sequences of different frequency bands was
      investigated. The possibility for the simultaneous registration of five responses
      to the stimuli with the central frequency of 0.5, 1, 2, 4, and 8 kHz has ben
      demonstrated.

PMID- 30113577
TI  - [Twenty years of clinical studies of GJB2-linked hearing loss in Russia].
AB  - The most common cause of congenital hereditary hearing loss was discovered 20
      years ago in 1997 when GJB2 gene was revealed in the first locus of recessive
      hearing loss DFNB1. It encodes protein connexin 26, a structural component of the
      intercellular channels. Recessive mutations in this gene cause the congenital
      bilateral sensorineural hearing loss. For many years the aim of our work was to
      study the prevalence and clinical manifestations of hereditary hearing loss. Our
      research can be divided into three stages. In the beginning, we investigated the
      prevalence of GJB2 mutations in a healthy population and in the people suffering
      from hearing impairment. Further research was conducted in the field of clinical
      manifestations and evidence of the congenital character of GJB2-related hearing
      loss. Currently, we are working on the prevalence of mild and moderate hereditary
      hearing loss and the probability of its progression. Achievements in molecular
      genetics make it possible to establish the hereditary character of congenital
      hearing loss and to avoid repeated family cases. Primary prevention of hereditary
      hearing loss becomes real by raising the awareness of GJB2 mutations carriers.

PMID- 30113578
TI  - [Epidemiology of hearing loss in children of the first year of life].
AB  - The aim of this study was the investigation of the epidemiology of permanent
      hearing impairment in the children of first year of life in the Russian
      Federation after the implementation of the newborn universal hearing screening
      program. The prevalence of hearing loss in children in the first year of life was
      estimated at 2.5 per 1,000 based on the official statistical data and reports of
      hearing rehabilitation centres in 2016. A cohort of 405 children born in 2012 was
      examined at the age from 0 to 4 years of life. Among them 276 children were
      diagnosed with permanent congenital and prelingual hearing loss. 88% of the cases
      were bilateral, sensorineural hearing loss confirmed in 84% of the cases. The
      genetic cause of hearing loss was revealed in 58% of the patients assessed for
      the presence of GJB2 gene mutations. In preterm infants, the permanent hearing
      loss was detected in 70% of the cases. The comprehensive audiological assessment
      before 3 months of life was conducted only in 32% of the children; this finding
      is not consistent with the international newborn hearing screening
      recommendations. Only 70% of the cases of congenital and preverbal hearing loss
      were diagnosed during the first year of life.

PMID- 30113579
TI  - [The application of the screening questionnaires for the diagnostics of the
      central auditory processing disorders in the pediatric practice].
AB  - Identification and diagnostics of auditory processing disorders (APD) in the
      children continues to be a challenge. Screening tools help to decide the need for
      evaluation. However, none of them are used routinely in Russia, nor are there
      thus far auditory checklist questionnaires in the Russian language. The aim of
      his study was to approve Children's Auditory Performance Scale (CHAPS) and
      Fisher's Auditory Checklist in Russian for the children at the age of 5-10 years.
      The study included 52 children at the age from 5 to 11 years. All of them were
      native Russian speakers. Pure tone audiometry, immitancemetry, and the Simplified
      RuMatrix test were performed for all the children. All of them had normal hearing
      thresholds, speech and language development, and normal academic achievement at
      school. The parents filled in the CHAPS and Fisher's Auditory Checklist
      questionnaires in Russian. The mean value of Fisher's Auditory Checklist was 85.7
      +/- 9.3, the mean value of CHAPS questionnaire was equal to 0.08 +/- 0.26. The
      results obtained with the use of the Russian language questionnaires are in
      excellent agreement with the test data yielded by the respective English language
      versions. It is recommended that the clinical assessment for APD should be
      performed for children with the result of the Fisher questionnaire less than 67
      points and with the result of the CHAPS questionnaire less than -1 point. It is
      concluded that Fisher's questionnaire was more convenient for the parents to fill
      in.

PMID- 30113580
TI  - [The management of patients with congenital malformations of the external and
      middle ear].
AB  - Rehabilitation of the patients suffering from with congenital malformations of
      external and middle ear is a specific area of medicine requiring special
      knowledge and skills of the audiologists and ear surgeons. This article
      highlights the issues of epidemiology, classification and methods for the
      rehabilitation of patients presenting with this pathology that reflect our own
      experience and the methodology based on it for all phases of both functional and
      aesthetic surgical inerventions. Special attention is given to the assessment of
      the effectiveness of the treatment, as part of the evaluation of the quality of
      medical services. The results were demonstrated in 56 patients aged from 5 to 17
      years. 32 of them underwent reconstructive, hearing improving surgery
      (meatotympanoplasty), 24 patients were managed by means of the implantation of
      the bone-anchored hearing systems. The assessment of the effectiveness of the
      treatment was conducted according to the algorithm developed by the authors,
      including free field pure tone audiometry and validated questionnaires for the
      assessment of the quality of life (the Glasgow Children's Benefit Inventory).

PMID- 30113581
TI  - [Changes of the auditory function in he children with chronic kidney failure].
AB  - : The risk factors that contribute to the development of hearing loss in the
      children with chronic kidney failure (CRF) are complications and/or
      manifestations of the disease itself as well as the side effects of its
      treatment. There are many similarities between the anatomical, physiological, and
      pharmacological features of the nephron and the striavascularis of the cochlea.
      The objective of the present study was the evaluation of the status of the
      auditory function in the children presenting with CRF. MATERIAL AND METHODS: A
      total of 62 children with CRF were examined. 40 patients were on peritoneal
      dialysis and 9 on hemodialysis whereas 13 children did not receive hemodialysis.
      Kidney was transplanted in 7 patients. The registration of transient evoked
      otoacoustic emission (TEOAE) was performed in all the children. For patients
      without TEOAE complex underwent the audiological examination. RESULTS: The TEOAE
      was not registered in 17 of the 62 examined children. According to the results of
      the comprehensive audiological examinations, 13 children suffered from the
      hearing loss of different forms and severity while 5 children presented with
      bilateral deafness. As the duration of CRF progressed, the patients became more
      prone to develop hearing impairment. Hearing loss is possibly genetically
      determined. Among the etiological factors underlying the development of the
      hearing loss the high doses of immunosuppressants and aminoglycosides are
      considered to be the principal ones.

PMID- 30113582
TI  - [The analysis of the association of the polymorphic variants of the TPMT, COMT,
      and ABCC3 genes with the development of hearing disorders induced by the
      cisplatin treatment].
AB  - Cisplatin and its derivatives are widely used chemotherapeutic agents for the
      treatment of many cancers, including hepatoblastoma, brain tumors, and germ-cell
      tumors. This therapy contributed to the dramatic increase in the survival rate.
      However, its use is restricted by the high incidence of irreversible ototoxicity
      associated with cisplatin application (in more than 60% of the children receiving
      it). Some studies have reported that genetic variants of TPMT (rs 12201199), COMT
      (rs4646316), and ABCC3 (rs 1051640) are conferring increased risk of developing
      cisplatin-induced hearing loss. However, in other studies the results were not
      replicated. In the present study, we replicated the previous studies based on an
      independent cohort of Russian patients. SNP genotypes for rs 12201199, rs4646316
      and rs 1051640 were determined in DNA samples obtained from 16 patients who
      developed hearing loss and a group of 34 patients whose hearing was retained. The
      association between TPMT (rs 12201199), COMT (rs4646316), and ABCC3 (rs 1051640)
      variants and the hearing loss was not observed in our cohort.

PMID- 30113583
TI  - [The effectiveness of the speech therapist and audiologist collaboration during
      speech processor fitting].
AB  - The aim of the study was to present the first clinical experience of clinical
      trials of new methodology of the CI speech processor fitting with the new
      software Nucleus Fitting Software - NFS. At all 4 fittings sessions there were 15
      children. During the fitting sessions 2 techniques were used - with the new NFS
      software and classical technique were used. The efficiency and need of
      collaboration of the speech therapist and the audiologist in the CI fitting
      sessions is proved. Results of inspection have shown that in 76.6% parents have
      established emotional cooperation with the children. Most of children have begun
      to seize the spontaneous speech in natural communication (60% - words, 23.3% -
      simple phrases). The results received by us allow to recommend the offered
      technique of the facilitated speech processor fitting technique for widespread
      introduction in clinical practice.

PMID- 30113584
TI  - [The significance of antistreptolysin O characteristics for the determination of
      indications for tonsillectomy in the children].
AB  - The objective of the present work was to evaluate the diagnostic significance of
      the measurement of the antistreptolysin O (ASLO) titers in the children
      presenting with chronic tonsillitis for determining the indications for
      tonsillectomy. The study included 54 patients at the age varying from 4 to 17
      years who had undergone bilateral tonsillectomy for the treatment of chronic
      tonsillitis. The diagnosis was confirmed by the results of the histological study
      of the removed amygdalae. Prior to surgery, all the patients had been subjected
      to the bacteriological investigation of the smears taken from the surface of the
      palatal tonsils. The titers of antistreptolysin O in the serum were determined
      with the use of the kinetic nephelometric technique before, 6 and 12 months after
      the surgical intervention. The results of the measurements were treated using the
      Statzilla software package (version 3.2, R Foundation for Statistical Computing,
      Vienna, Austria). Streptococcus pyogenes (group A) was identified only in 7 (13%)
      patients. The initially enhanced content of ASLO ranging from 273 to 1880 IU/ml
      was documented in 42 (77.7%) of the 54 patients. Twelve patients had the ASLO
      titers within the normal limits (from 13 to 124 IU/ml). The removal of palatal
      tonsils resulted in a significant decrease of the ASLO titers in the patients who
      had presented with the initially enhanced content of antistreptolysin O (p <
      0.05); nevertheless, their ASLO titers remained higher than the normal values in
      69% and 82% of the patients examined within 6 and 12 months after the surgical
      intervention, respectively. The patients who had exhibited the high levels of
      antistreptolysin O during the preoperative period did not experience
      normalization of this parameter after surgery. It is concluded, taking into
      account the absence of correlation between the enhancement of serum
      antistreptolysin O titers and the presence of group A beta-chemolytic
      Streptococci (BCSA), that the result of the measurement of ASLO titers can not be
      considered as a valid indication for tonsillectomy in the children.

PMID- 30113585
TI  - [Organizational aspects of the improvement of the effectiveness of the research
      and practical activities in otorhinolaryngology].
AB  - The authors discuss the problems pertaining to the methods for the improvement of
      the effectiveness of the research and practical activities in otorhinolaryngology
      and public health care at large. Special attention is given to the elaboration
      and implementation of the flexible approaches to the management of on-going
      research activities and initiatives, the development of horizontal
      complementarity, and the capability of the scientific groups for self
      organization with a view to efficacious achievement of the assigned goals. The
      model of the research work based on the cluster strategy is presented as
      exemplified by organization of these activities at the L.I. Sverzhevskiy Research
      Institute of Clinical Otorhinolaryngology, Moscow. The model makes possible the
      effective interaction of the institute with other research institutions and
      industrial enterprises, it promotes the large-scale implementation of the newly
      developed innovative products.

PMID- 30113586
TI  - [New criteria of radical surgery and long-term outcomes of hilar
      cholangiocarcinoma management].
AB  - AIM: To develop new criteria of radical surgery for hilar cholangiocarcinoma
      (HCC). MATERIAL AND METHODS: There were 165 HCC patients who underwent surgery in
      1986-2016 at the Vishnevsky Institute of Surgery. TNM stage distribution: stage I
      - 4 (2.4%), II - 45 (27.3%) (29 of them are referred to the 1st period of work),
      IIIA - 23 (13.9%), IIIB - 41 (24.8%), IVA - 35 (21.2%), IVB - 17 (10.3%). 80
      (48%) patients underwent hemihepatectomy, 17 (10%) - advanced hemihepatectomy, 16
      (10%) - minor liver resection with common bile duct repair, 52 (32%) - common
      bile duct repair resection. Kaplan-Meier survival analysis was performed. Cox
      proportional hazard model was applied to access relationship between survival and
      prognostic factors. Log-rank test was used to compare both survival curves.
      RESULTS: R0-resection as followed by 5-year survival rate near 32%. Microvascular
      invasion was observed in 42.9%, lymphovascular invasion - in 88.2%, positive
      resection margin - in 59.2%, perineural invasion - in 83.3%, cells in surrounding
      fatty tissue were revealed in 92.3%. Resection may be considered radical (R0) if
      all variables are absent, 5-7 negative factors are followed by conditionally
      radical procedure (R+number of positive factors). Long-term outcomes and
      significance of new criteria were accessed (p=0.004). CONCLUSION: New criteria of
      radical procedure are presented. The last reflects the concept of dependence of
      'pure' surgical edge from not only presence or absence of tumor cells in cut-off
      plane but also from important morphological features of tumor.

PMID- 30113587
TI  - [Surgical resolutions determining outcomes of infected pancreatic necrosis].
AB  - AIM: To evaluate technology, indications and time of minimally invasive semi
      closed and laparotomic sanations for infected pancreatic necrosis (IP). MATERIAL
      AND METHODS: Initially it was used sonography-assisted minimally invasive semi
      closed drainage of IP with gradual augmentation of catheters' diameter. In 462
      patients with IP liquid pus prevailed over sequesters in epigastric localized
      pancreatonecrotic phlegmon (ELPF) and pancreatonecrotic abscesses. So, minimally
      invasive approach may be definitive. Epigastric advanced pancreatonecrotic
      phlegmon with predominant sequesters is often followed by conversion to
      transverse omentobursopancreatostomy (OBPS) to open all purulent accumulations.
      RESULTS: Surgical treatment immediately after parapancreatic infiltrate
      suppuration (i.e. within 3-4 weeks after onset of the disease) is associated with
      reduced mortality. Absent result of minimally invasive drainage is followed by
      mortality from the 11th day and maximum in 14 days after treatment onset.
      Therefore, focal IP resistant to minimally invasive drainage requires conversion
      to transverse OBPS or video-assisted sequestrectomy after 10-13 days. The lowest
      mortality (14.8+/-2.5%) was observed in patients who underwent minimally invasive
      drainage or transverse OBPS within 10-13 days. Ineffective prolonged minimally
      invasive drainage was accompanied by high mortality rate (60.7+/-3.2%, p<0.001).
      CONCLUSION: Conversion to transverse OBPS or video-assisted sequestrectomy are
      required if minimally invasive drainage of IP is ineffective after 10-13 days.
      Clear understanding of indications for closed and open drainage of PI helps to
      avoid tactical and technological errors.

PMID- 30113588
TI  - [Influence of biliary decompression technique on the outcomes of reconstructive
      surgery].
AB  - AIM: To evaluate bile ducts injuries and effect of biliary decompression
      technique on the outcomes of reconstructive surgery. MATERIAL AND METHODS: There
      were 21 patients with biliary injury during cholecystectomy, 20 patients with
      cholelithiasis, and 1 patient after surgery for perforated duodenal ulcer. Their
      age was 22-81 years (mean 54.3 years). Primary surgery through median laparotomy
      was followed by biliary injury in 12 patients, laparoscopic cholecystectomy - in
      6 patients, open laparoscopy - in 3 patients. Patients were divided into 2
      groups. In group 1 (n=11) biliary injury was diagnosed intraoperatively, in group
      2 (n=10) - in 2-11 days after primary procedure. According to European
      Association for Endoscopic Surgery (EAES) 2013 classification biliary injury type
      1 was found in 5 patients, type 2 - in 9 cases, high damage involving confluence
      (type 3) - in 1 patient, type 4 - in 1 patient, and type 6 - in 5 patients.
      Endoscopic retrograde cholangiopancreatography in 3 patients revealed that
      biliary drainage output after laparoscopic cholecystectomy was caused by cystic
      duct clipping failure, endoscopic papillosphincterotomy was successfully used for
      biliary drainage output (type 6). In 3 patients operated through median
      laparotomy biliary excretion cessation was observed after 2-3 days that indicated
      damage of aberrant bile ducts. RESULTS: Bile outflow into gastrointestinal tract
      was restored in 11 out of 16 patients with iatrogenic biliary injury types 1-4,
      external biliary drainage was used in 4 patients due to their severe condition
      and abdominal inflammatory changes. Biliary fistulae occurred in 5 out of 8
      patients in both groups after primary reconstructive surgery. Biliary stricture
      was observed in 3 cases due to external biliary drainage failure followed by
      peritonitis. 7 patients underwent reconstructive surgery with positive result.
      Mortality was absent. In 1 patient with biliary fistula outcome is unknown.
      CONCLUSION: Transumbilical biliary drainage is optimal during reconstructive
      surgery.

PMID- 30113589
TI  - [Microbiological profile of postoperative infection in current oncology surgery].
AB  - AIM: To analyze in-hospital infection in oncology center within 2012-2016.
      MATERIAL AND METHODS: There were 98 patients with nosocomial infection who
      underwent surgery for malignancies. Microbiological examination of biological
      materials was carried out by appropriate laboratories according to generally
      accepted methods. RESULTS: Mono- and polymicrobial infection was observed in 58
      and 42% of cases. Staphylococcus aureus was the most common agent in patients
      with microbial infection. Minimal inhibitory concentration of vancomycin (MIC)
      >=1.0 MUg/ml was revealed in 60% of microbes. Microbial agents isolated were
      resistant to antibacterial drugs used to prevent postoperative infectious
      complications. CONCLUSION: In-hospital infection was accompanied by staphylococci
      as a rule. Causative agents of nosocomial infections are usually resistant to
      conventional antibacterial drugs. Moreover, 60.1% of microbes had minimal
      inhibitory concentration of vancomycin >=1.0 MUg/ml that indicated the need for
      alternative therapeutic agents.

PMID- 30113590
TI  - [Comparative diagnostic value of various methods of intracavitary pressure
      measurement in abdominal compartment syndrome].
AB  - AIM: To investigate diagnostic value of various methods of biophysical somatic
      parameters (BSP) monitoring in peritonitis complicated by abdominal compartment
      syndrome. MATERIAL AND METHODS: 220 patients with advanced peritonitis
      complicated by compartment syndrome were enrolled. Sensitivity, specificity,
      diagnostic value of the measurement of intraabdominal, intraintestinal,
      intrathoracic pressure, paravulnar tissues tension depending on abdominal
      hypertension severity were determined. RESULTS: BSP control including
      intraabdominal, intraintestinal, intrathoracic pressure and paravulnar tissues
      tension is effective for BPS disturbances diagnosis and abele to detect them
      significantly more often (p=0.037) compared with M. Cheatham's method alone.

PMID- 30113591
TI  - [Diaphragmatic hernia in elective thoracic surgery].
AB  - AIM: To clarify the indications for reconstructive surgery in patients with
      diaphragmatic hernia. MATERIAL AND METHODS: Retrospective trial has included 36
      patients with diaphragmatic hernia for the period 1963-2017. There were 23
      (63.9%) women and 13 (36.1%) men. The majority of patients (83%) underwent
      surgery at able-bodied age (18-60 years). 27 (75%) patients had hernia of weak
      diaphragmatic zones, 9 (25%) - posttraumatic hernia. Diaphragm repair was
      performed with primary suture. In 2 cases of posttraumatic hernia mesh
      endoprosthesis was used. RESULTS: All patients were discharged. Postoperative
      complications arose in 4 (11.1%) patients, including 2 cases of mesh
      endoprosthesis deployment. Long-term outcome was followed-up in 15 patients from
      6 months to 17 years. Recurrent hernia was absent in all cases. CONCLUSION:
      Primary suture is acceptable for diaphragmatic hernia repair. Alloplastic repair
      is indicated for large defect, when primary suture is impossible or risk of its
      failure is high.

PMID- 30113592
TI  - [Hemostatic changes in patients with peripheral artery disease before and after
      bypass surgery].
AB  - AIM: To assess intrinsic coagulation pathway factors activity and hemostatic
      markers of endothelial dysfunction in patients with peripheral artery disease
      (PAD) before and after lower extremity bypass surgery. MATERIAL AND METHODS: 80
      patients with PAD Fontaine grade IIB-III were enrolled. 40 patients underwent
      open aorto-femoral-popliteal repair (group A) and 40 patients - medication (group
      B). Before and in 3 months after surgery peripheral venous blood samples were
      collected to assess the activity of factors VIII, IX, XI, von Willebrand factor
      (VWF), protein C (PrC), and metabolites of nitric oxide II (NO). RESULTS:
      Increased preoperative activity of VIII, IX, XI, and VWF factors compared with
      normal values was observed in group A. After 3 months there was an additional
      increase of VIII and VWF factors' activity. Activity of IX and XI factors
      remained increased on background of reduced level of NO metabolites. In group B
      increased activity of IX, XI, and VWF factors was revealed while levels of NO
      metabolites and PrC were normal. CONCLUSION: Thus, PAD is followed by
      prothrombotic state especially in patients after surgery. Surgical procedures are
      associated with more severe hypercoagulation.

PMID- 30113593
TI  - [Critical ischemia of hip stump. Incidence, clinical significance and diagnosis].
AB  - AIM: To study the incidence of hip stump ischemia, risk factors for 5-year
      survival after amputation, clinical features and diagnosis of this complication.
      MATERIAL AND METHODS: 1287 patients with peripheral artery disease followed by
      hip amputation were examined within 1997-2015. 50 of them had stump ischemia.
      RESULTS: It was found that hip stump ischemia occurs in 5.2% of cases and
      significantly aggravates 5-year survival. Transcutaneous oxygen tension less than
      20 mm Hg is reliable hemodynamic criterion of ischemia.

PMID- 30113594
TI  - [The role of in-hospital protocols in diagnosis and treatment of ulcerative
      gastroduodenal bleeding].
AB  - AIM: To improve immediate results in patients with acute ulcerative
      gastroduodenal bleeding. MATERIAL AND METHODS: The study enrolled 91 patients
      with ulcerative gastroduodenal bleeding. RESULTS: Diagnostic and curative
      procedures should be related to hospital's equipment, specialists' qualification
      and comprehensive development and application of accepted tactical approaches. 20
      year development of this protocol which includes original low-temperature
      irrigator of stomach and duodenal mucous membranes, objective choice of
      endoscopic hemostasis technique depending on bleeding source in gastroduodenal
      wall, early administration of proton pump inhibitors significantly increases
      efficacy and reliability of endoscopic hemostasis. It was followed by improved
      early outcomes: recurrent bleeding incidence was 4.2%, surgical activity
      decreased by 68% up to 13.2%, overall and postoperative mortality was 2.2% and
      8.3% respectively.

PMID- 30113595
TI  - [Standardization of intensive therapy tactics for acute hepatic insufficiency in
      patients with liver cirrhosis after portosystem shunting].
AB  - AIM: Here we analyze efficiency of the algorithm for intensive therapy of acute
      hepatic insufficiency in patients with cirrhosis after portosystemic shunting,
      based on the experience of the Republican Specialized Scientific and Practical
      Medical Center of Surgery named after academician V.V. Vakhidov and considering
      recommendations of the world's leading hepatology schools. MATERIAL AND METHODS:
      Algorithm efficiency was analyzed based on the results of portosystemic shunting
      of 556 patients with cirrhosis and acute liver insufficiency. Treatment
      effectiveness was assessed by presence and severity of postoperative
      complications, such as hepatic insufficiency and hepatic encephalopathy. Initial
      decompensation of liver cirrhosis significantly increases the risk of
      postoperative complications of portosystemic shunting due to edematous ascites
      syndrome - liver insufficiency (13.5% vs 6.9% in patients without ascites
      p>=0.05) and hepatic encephalopathy (64.9% vs. 51,7%, respectively, p>=0.05). In
      group of patients with preoperative ascites syndrome mortality rate was 3.8% (10
      patients) and in the group without ascites - 2.3% (6 patients). The main cause of
      early postoperative lethality was anastomotic thrombosis development with
      recurrence of bleeding from esophagus and stomach varicose veins. To reduce the
      risk of postoperative complications and lethality, a therapeutic-tactical
      algorithm was developed which was effective in combination with a complex of
      conservative and biophysical methods of treatment and aimed at eliminating the
      'resolving factors' of their developmen. RESULTS: One of the most important
      components of this algorithm is pharmacotherapy with hepatoprotective drugs use
      in patients with liver cirrhosis in the postoperative period to maintain liver
      functional state. Considering the antihypoxic, detoxifying and antioxidant
      properties of active components of remaxol and revealed positive effect of its
      use in patients (decrease in bilirubin level, increase in albumin fraction of
      total blood protein and decrease in activity of ALAT and ASAT in 2 times), this
      drug can be recommended for inclusion in the postoperative pathogenetic standard
      therapy in this category of patients.

PMID- 30113596
TI  - [Intrapancreatic accessory spleen].
AB  - BACKGROUND: Accessory spleen is the human growth anomaly, which appears in
      embryogenesis and frequently becomes an accidental finding during prophylactic
      medical examination. Pancreatic tail - the second frequent localization after the
      splenic hilus. Intrapancreatic accessory spleen can mimic the pancreatic tumor.
      AIM: To demonstrate case series of intrapancreatic accessory spleen in course of
      differential diagnostic with pancreatic neuroendocrine tumor and metastasis of
      renal - cell cancer. MATERIAL AND METHODS: Three patients with intrapancreatic
      accessory spleen were observed in abdominal department #1 A.V.Vishnevsky
      Institute of Surgery, - two females and one male. RESULTS: Two patients were
      surgically treated: in the first case basing on preoperative anamnesis and
      diagnostic data diagnosis of renal - cell cancer metastasis was established, in
      the second case - nonfunctional pancreatic neuroendocrine tumor. In both cases
      robotic distal pancreatectomy was performed. There were no conversions.
      Postoperative recovery was accompanied by clinicaly not relevant pancreatic
      fistulas, which didn't increase length of hospitalization. In the third case
      during CT and MRI diagnosis of intrapancreatic accessory spleen was determined.
      Surgical treatment wasn't performed. Control examination showed an absence of
      dynamic of characteristics and growth. CONCLUSION: Described cases demonstrate
      difficulty of differential diagnostics of tumor - like mass. Neuroendocrine
      tumors, renal - cell cancer metastases, solid pseudopapillary neoplasms and
      accessory spleen can have similar CT-characteristics. In appearance of
      differential diagnostic difficulties minimally invasive surgical treatment has to
      be performed.

PMID- 30113597
TI  - [Surgical treatment of patient with chronic pancreatitis complicated by
      bleeding].

PMID- 30113598
TI  - [Valve sparing aortic root replacement (David Procedure) in 36 year - old woman
      with the Marfan syndrome at the 27th week of pregnancy].
AB  - The article presents a clinical case of valve sparing aortic root replacement
      (David Procedure) in 36 year - old woman with the Marfan syndrome at the 27th
      week of gestation followed by successful prolongation of pregnancy. Indications
      for reconstructive intervention with cardiopulmonary bypass were: severe aortic
      valve insufficiency, Sinus of Valsalva Aneurysm (66 mm) and the ascending aorta
      dilatation (53 mm) with a rapid increase of aortic root dimension (12 mm during 9
      weeks). The patient underwent a valve sparing aortic root replacement according
      to David procedure using Gelweave Valsalva graft (Vascutec) No 28 The time of
      cardiopulmonary bypass was 137 minutes; the time of aortic cross-clamping was 107
      minutes. The patient was discharged from the hospital in a satisfactory condition
      in 21 days after the operation. Pregnancy was prolonged and ended with a planned
      cesarean section at 38 weeks of gestation, the birth of a boy with an Apgar score
      of 7/8.

PMID- 30113600
TI  - [Stomach carcinoid as a cause of severe gastrointestinal bleeding].

PMID- 30113599
TI  - [Diagnosis of a sonographically negative extensive defect of the lig.falciforme
      hepatis].
AB  - This study assess the US diagnose of very rate extensive trapezoidal defect
      lig.falciforme hepatis. 2 patients with this condition were examined.
      Transabdominal ultrasound of this condition was unsuccessful, specific
      sonographic features of the defect is not revealed.

PMID- 30113601
TI  - [Reality and prospects of sepsis epidemiology research].
AB  - Current foreign and Russian literature for sepsis epidemiology is reviewed. There
      is advanced incidence of sepsis in developing countries among young people as a
      rule. Absent high-quality epidemiological studies lead to overdiagnosis of sepsis
      and increased morbidity. National and territorial screening and diagnostic
      programs for sepsis became possible with introduction of new recommendations
      'Sepsis-3'. Thus, there is a possibility to systematize regular epidemiological
      studies devoted to sepsis.

PMID- 30113602
TI  - [Imaging of neoangiogenesis of internal carotid artery's atherosclerotic plaque
      by contrast-enhanced sonography and histological examination].
AB  - Previously, atherosclerosis was considered a disease accompanied exclusively by
      lipids accumulation. At present time success of fundamental and experimental
      science confirmed that atherosclerotic process is also associated with
      neovascularization and prolonged inflammatory response at all stages of
      atherogenesis from initial manifestations to thrombotic complications. The cause
      of atherosclerotic plaque instability is neovascularization, which is accompanied
      by intra-plaque hemorrhage and damage. Complications of carotid arteries
      atherosclerosis are strokes and transient ischemic attacks. The use of a wide
      range of diagnostic and pathohistological techniques is required for assessing
      this pathology. The most promising diagnostic technique is Contrast Enhanced
      Ultrasonography (CEUS) which allows to assess neovascularization degree in
      atherosclerotic plaque through the injection of a contrast agents.

PMID- 30113603
TI  - Immediate Postextraction Screw-Retained Partial and Full-Arch Rehabilitation: A 3
      Year Follow-up Retrospective Clinical Study.
AB  - The aim of this study was to document the performance of a novel technique
      (OnlyOne), involving immediate restoration of postextraction implants supporting
      a partial or full-arch restoration. A retrospective analysis of patients with at
      least 3 years of follow-up was performed. Implants were tilted mesiodistally and
      vestibulopalatally according to the available bone. Prosthetically guided
      definitive abutments were connected at surgery and never disconnected. Anorganic
      bovine bone grafting was done to preserve the buccal bone and the ridge contour.
      Patients received a screw-retained provisional prosthesis within 24 hours of
      surgery and a final screw-retained prosthesis within 1 year. Prostheses emerged
      from natural soft tissue. Clinical and radiographic evaluation was routinely
      performed. A total of 70 patients received 153 implants in fresh extraction
      sockets. The mean follow-up was 38.0 +/- 3.0 months (range 36 to 51 months). One
      implant failed at the 3-year follow-up. Implant survival was 99.3%. Marginal bone
      level change averaged -0.68 +/- 1.2 mm at the last radiographic control.
      Immediate placement and restoration of implants designed for high primary
      stability with a definitive abutment placed at surgery and final screw-retained
      prosthesis with no artificial gingiva is a viable procedure with excellent medium
      term outcomes.

PMID- 30113604
TI  - Three-Year Results of a Randomized Controlled Clinical Trial Using Submucosally
      Veneered and Unveneered Zirconia Abutments Supporting All-Ceramic Single-Implant
      Crowns.
AB  - This study aimed at evaluating the influence of veneering of the submucosal part
      of zirconia abutments on biologic, radiographic, technical, and esthetic outcomes
      in single-tooth implant sites. A total of 20 patients each received a zirconia
      abutment to support an all-ceramic implant-supported crown. Patients were
      randomly assigned to the test group (n = 10), in which the abutment was modified
      with pink veneering ceramic, or to a control group (n = 10) without further
      submucosal customization. Patients were followed up at baseline (after the
      insertion of the final reconstruction) and yearly thereafter. Wilcoxon-Mann
      Whitney test was used to evaluate the difference between the medians of the two
      groups, whereas Wilcoxon signed rank test allowed calculation of the differences
      per group. At 3 years, 18 patients could be recalled. The survival rates reached
      100% (implant level) and 95% (restorative level). Two implant crowns experienced
      minor chipping, one in each group. No significant intergroup differences were
      observed regarding mucosa thickness between the groups. The width of keratinized
      tissue did not change significantly over time in either group. The radiographic
      evaluation showed no significant differences regarding the marginal bone level at
      any timepoint between the groups. Changes over time reached -0.27 mm (SD 0.41,
      median -0.26) for the test group and -0.21 mm (SD 0.30, median -0.31) for the
      control group. Statistical significance was not reached within or between the
      groups. Veneering of the submucosal part of zirconia abutments did not
      significantly influence biologic and technical outcomes in single-tooth implant
      sites up to 3 years.

PMID- 30113605
TI  - Treatment Outcome of Posterior Composite Indirect Restorations: A Retrospective
      20-Year Analysis of 525 Cases with a Mean Follow-up of 87 Months.
AB  - The purpose of this study was to evaluate the survival of 525 composite indirect
      restorations in premolars and molars after a follow-up of 20 years. For each
      patient, the following variables were recorded and analyzed: age, sex, smoking
      status, presence of plaque according to O'Leary index, and presence of bruxism.
      For each restoration, the following variables were collected: restoration class,
      tooth type (premolar or molar), and restoration material. Mean 20-year survival
      rate of composite restorations was 57%, ranging from 44% to 75%. The Kaplan-Meier
      method demonstrated a probability of survival at 10 years of 80% and 90%.
      Surviving restorations kept their clinical characteristics extremely well, as
      assessed on the basis of the United States Public Health Service criteria. The
      results of this study demonstrate the efficacy of indirect composite
      restorations, confirming their reliability as a posterior prosthetic clinical
      option.

PMID- 30113606
TI  - Surgical Alternatives for Treating Peri-implantitis.
AB  - The objective of this case series was to describe surgical approaches that can be
      used to efficiently and effectively treat peri-implantitis as measured by
      positive changes in clinical parameters. A total of 32 patients with 45 implants
      were treated surgically to eliminate peri-implantitis. Baseline clinical
      parameters measured prior to surgery were compared to those made 6 months
      postsurgery to evaluate the efficacy of each procedure. Implants demonstrating
      signs of peri-implantitis were treated by one of three approaches: (1)
      regenerative surgery, (2) osseous resective surgery, or (3) apically repositioned
      flap surgery. In all instances, the exposed implant surfaces were debrided and
      decontaminated. Relative to baseline values, regenerative surgery yielded
      statistically significant changes in probing depth (PD) (7.21 +/- 0.27 mm to 4.09
      +/- 0.14 mm) and percentage of sites exhibiting bleeding on probing (BoP) (100.0%
      +/- 0.0% to 10.6% +/- 3.3%) as measured at the 6-month recall visit (P <= .05).
      The decrease in probing depth was not dependent on the type of graft material
      used (P <= .05). Resective surgery yielded statistically significant changes in
      PD (5.86 +/- 0.23 mm to 3.63 +/- 0.14 mm) and the percentage of sites exhibiting
      BoP (100.0% +/- 0.0% to none) (P <= .05). Finally, the implants treated via
      apically repositioned flap surgery demonstrated statistically significant
      decreases (P <= .05) in both PD (6.79 +/- 0.27 mm to 4.32 +/- 0.16 mm) and BOP
      (100.0% +/- 0.0% to 14.3% +/- 6.7%) (P <= .05). Regenerative, resective, and
      apically positioned flap surgery can be utilized to successfully treat peri
      implantitis.

PMID- 30113607
TI  - A Two-Step Surgical Approach with Flattening of the Root Surface to Treat
      Localized Gingival Recessions Affecting Mandibular Incisors: A Case Series
      Report.
AB  - Root coverage in the anterior mandible is challenging due to a thin gingiva,
      shallow vestibule, and/or high frenulum. This case series reports on the
      flattening of the root surface to create a new emergence profile conceived with a
      two-step surgical approach aimed at providing more space for the graft,
      increasing the thickness of the gingival margin, and getting extra soft tissue in
      the open area of the recession. A total of 10 patients with recessions affecting
      the mandibular incisors were treated to evaluate this two-step approach, which
      included odontoplasty of the root followed by a connective tissue graft. At 1
      year, the mean coverage was 100% in Class II recessions, and 80.5% in Class III.
      The mean keratinized tissue increase was 5.80 +/- 1.75 mm. This surgical approach
      could be proposed as an alternative when treating mandibular anterior teeth with
      root prominence or with a buccally tilted position.

PMID- 30113608
TI  - Evaluation of Health or Pathology of Bilateral Maxillary Sinuses in Patients
      Referred for Cone Beam Computed Tomography Using a Low-Dose Protocol.
AB  - The aim of this study was to evaluate the health or pathology of bilateral
      maxillary sinuses using cone beam computed tomography (CBCT) with a low-dose
      protocol, and to analyze potential influencing factors. The study included only
      CBCT scans with complete visualization of bilateral maxillary sinuses. The scans
      were taken using a medium to large field of view and a low-dose protocol, as
      indicated by the manufacturer. CBCT images were analyzed with regard to the
      morphology of the sinus membrane and surrounding bone twice by one observer.
      Influencing factors such as age, sex, or status of the remaining dentition in the
      posterior maxilla, including periodontal and endodontic parameters, were
      evaluated. The study included 134 CBCT scans (268 maxillary sinuses). Using a low
      dose protocol, intraobserver reliability of the measurements was almost perfect
      (kappa value range 0.875 to 1). More than half the sinuses evaluated (63.1%) did
      not show visible morphologic changes. The most frequently identified pathologic
      appearance was a flat, shallow thickening of the sinus membrane of > 2 mm (47
      positive findings [17.5%]). Only 15 (5.6%) sinuses were associated with teeth
      with endodontic treatment and/or pathology, and 10 (3.7%) with teeth exhibiting
      periodontal pathology. CBCT scans with a low-dose protocol can be recommended as
      a feasible adjunctive tool to evaluate health or pathology of the maxillary
      sinuses prior to surgical interventions such as sinus floor augmentation. Of all
      morphologic changes seen, only a small portion of the cases were considered to
      need further medical diagnosis/treatment.

PMID- 30113609
TI  - Changes in Peri-implant Soft Tissue Thickness with Bone Grafting and Dermis
      Allograft: A Case Series of 15 Consecutive Patients.
AB  - Immediate implant placement and provisional restoration has become a popular and
      well-supported method of tooth replacement in the maxillary anterior dentition.
      Aside from achieving osseointegration, esthetic demands have grown with better
      understanding of the behavior of hard and soft tissues following this mode to
      therapy. Stability of gingival contours, texture of the surrounding tissues, and
      blending of prosthetic components with the natural dentition are critical for
      successful outcomes to be maintained long-term. Increasing soft tissue thickness
      at the time of therapy plays an important role in this regard. A technique
      combining the proven principles of immediate implant placement and provisional
      restoration with hard and soft tissue augmentation using nonautogenous materials
      is demonstrated with comparisons to nongrafted, temporized historical controls.

PMID- 30113610
TI  - Resective Treatment of Peri-implantitis: Clinical and Radiographic Outcomes After
      2 Years.
AB  - A prospective case series was performed to examine the clinical and radiographic
      changes to peri-implant tissues 2 years after resective treatment of peri
      implantitis, including an apically positioned flap, osteoplasty, and
      implantoplasty. In total, 25 patients with 40 titanium implants of multiple
      brands and advanced peri-implantitis were included in this study. After 2 years,
      all implants survived, mean probing pocket depth was reduced from 8.7 to 3.3 mm,
      and bone level remained stable in 92.5% of the implants. Findings suggest the
      approach of an apically positioned flap combined with osteoplasty and
      implantoplasty as an effective and reliable strategy against peri-implantitis,
      although increased gingival recessions may limit its application in esthetic
      areas.

PMID- 30113611
TI  - Nanomaterial based electrochemical sensors for the safety and quality control of
      food and beverages.
AB  - The issue of foodborne related illnesses due to additives and contaminants poses
      a significant challenge to food processing industries. The efficient, economical
      and rapid analysis of food additives and contaminants is therefore necessary in
      order to minimize the risk of public health issues. Electrochemistry offers
      facile and robust analytical methods, which are desirable for food safety and
      quality assessment over conventional analytical techniques. The development of a
      wide array of nanomaterials has paved the way for their applicability in the
      design of high-performance electrochemical sensing devices for medical
      diagnostics and environment and food safety. The design of nanomaterial based
      electrochemical sensors has garnered enormous attention due to their high
      sensitivity and selectivity, real-time monitoring and ease of use. This review
      article focuses predominantly on the synthesis and applications of different
      nanomaterials for the electrochemical determination of some common additives and
      contaminants, including hydrazine (N2H4), malachite green (MG), bisphenol A
      (BPA), ascorbic acid (AA), caffeine, caffeic acid (CA), sulfite (SO32-) and
      nitrite (NO2-), which are widely found in food and beverages. Important aspects,
      such as the design, fabrication and characterization of graphene-based materials,
      gold nanoparticles, mono- and bimetallic nanoparticles and metal nanocomposites,
      sensitivity and selectivity for electrochemical sensor development are addressed.
      High-performance nanomaterial based electrochemical sensors have and will
      continue to have myriad prospects in the research and development of advanced
      analytical devices for the safety and quality control of food and beverages.

PMID- 30113612
TI  - The local structure in the BmimPF6/acetonitrile mixture: the charge distribution
      effect.
AB  - The changes of the local structure in the binary mixture of 1-butyl-3
      methylimidazolium hexafluorophosphate (BmimPF6) ionic liquid and acetonitrile are
      investigated over the entire composition range. Two charge distribution models of
      the ions are considered: in the first one, the atomic fractional charges of the
      cations and anions are kept equal with those in the neat ionic liquid, and hence
      they are independent from the mole fraction of the ionic liquid, while in the
      second one the charge distribution is scaled up by a mole fraction dependent
      factor. The sum of these charges converge to +1e and -1e on the cation and anion,
      respectively, at infinite dilution. All the other interactions and geometry
      parameters of the ions (i.e., Lennard-Jones, bond stretching, angle bending and
      dihedral parameters) are identical in the two cases. The effect of the fractional
      charge distribution on the hydrogen bonding between the counterions themselves
      and between the ions and solvent molecules, as well as on the stacking
      interactions between the cations, is analyzed. To this end, two distances,
      characteristic of the hydrogen bond formed by the donor moiety and its nearest
      neighbor acceptor, as well as a coordinate system that defines unambiguously the
      orientation between a reference cation and its nearest neighbor, are introduced.
      It is shown that, with the variable charge model, the neighboring cation-anion
      pairs maintain their relative arrangement similar to the neat ionic liquid down
      to an ionic liquid mole fraction of xIL = 0.10, whereas in the case of the
      constant charge model such changes occur already at xIL = 0.20. Furthermore, the
      analysis of the first and the second nearest neighbor distance distributions of
      an anion around a reference cation indicates that, at this mole fraction range,
      there are two different preferred arrangements of the anions around the cations.
      In the first one, similarly to the local structure around a reference cation in
      the neat ionic liquid, the anion forms a distorted hydrogen bond with the cation,
      while in the second one the anion is located farther from the cation, forming no
      hydrogen bond with it. The relative population of these two types of preferred
      nearest neighbor cation-anion arrangements is found to be sensitive to further
      decrease of the ionic liquid mole fraction. These findings correlate with
      experimental results concerning the behavior of many physical chemical properties
      (e.g., excess volume, excess viscosity, chemical shift, infrared and Raman
      vibrational mode shifts, diffusion, etc.) that were found to undergo a drastic
      change in this mole fraction range. Our results show that in this composition
      range a transition occurs from the situation where the macroscopic physical
      chemical properties of the system are determined primarily by the cation-anion
      hydrogen bonding interactions to that where they are determined by the solvation
      of the cation and the anion by the molecular solvent.

PMID- 30113613
TI  - Comparing gas transport in three polymers via molecular dynamics simulation.
AB  - People use polymers as materials for preparing separation media or containers. It
      is necessary to have a molecular level profound knowledge of gas transport in e
      bulk and interface regimes of different polymers, but few researchers have done a
      molecular level study of the bulk and interface behavior of gases in several
      types of non-homologen polymers thoroughly or developed expressions to correlate
      gas transport properties with cavity size distribution and chain oscillation
      flexibility. Therefore, in this work, molecular dynamics (MD) simulation was
      employed to study the transport of methane and n-butane molecules in the bulk and
      interface region of polyethylene (PE), poly(4-methyl-2-pentyne) (PMP) and
      polydimethylsiloxane (PDMS). Penetrant diffusivity, solubility and permeability
      in the bulk were studied first. The subdiffusion behavior of gas molecules is
      explored to obtain the mechanisms behind penetrant transport. Both penetrants
      have much smaller diffusivities in PE than in PMP and PDMS, and they have larger
      diffusivities in PDMS than in PMP. PE has lower accessible cavity fraction (ACF)
      and average oscillation amplitudes (AOAs) of the chains than PDMS and PMP. PE
      also has much smaller solubilities and permeabilities of both penetrants than
      PDMS and PMP. Though the permeabilities of both penetrants in PDMS are higher
      than the corresponding values in PMP, PMP has a higher selectivity of n-butane
      over methane than PDMS. Nonequilibrium MD simulation was performed to study the
      interface property and gas transport in the interface region. Equations to
      predict penetrant diffusivity and permeability from the accessible cavity
      fraction (ACF) and average amplitude of chain oscillation were developed
      successfully. Penetrant diffusivity and permeability are proportional to the
      value of ACF to the power of one third and that of ACF to the power of four
      thirds, respectively.

PMID- 30113614
TI  - Investigation of failure behavior of a thermoplastic elastomer gel.
AB  - Gels are increasingly being used in many applications, and it is important to
      understand how these gels fail subjected to mechanical deformation. Here, we
      investigate the failure behavior of a thermoplastic elastomer gel (TPEG)
      consisting of poly(styrene)-poly(isoprene)-poly(styrene) in mineral oil, in
      tensile mode, under constant stress, and in fracture tests, where the fracture
      initiates from a predefined crack. In these gels, the poly(styrene) endblocks
      associate to form spherical aggregates, as captured using SAXS. Shear-rheology
      experiments indicate that the poly(isoprene) midblocks connecting these
      aggregates are loosely entangled. The relaxation behavior of these gels has been
      captured by time-temperature superposition of frequency sweep data and stress
      relaxation experiments. The relaxation process in these gels involves endblock
      pullout from the aggregates and subsequent relaxation of the chains. An
      unfavorable enthalpic interaction between the endblock and mineral oil results in
      a significantly large relaxation time. These gels display rate dependent
      mechanical properties, likely due to the midblock entanglements. Fracture and
      creep failure tests provide insights into the gel failure mechanism. Creep
      experiments indicate that these gels fail by a thermally activated process.
      Fracture experiments capture the energy release rate as a function of crack-tip
      velocity. The critical energy release rate is estimated by incorporating the
      friction force the polystyrene chains are subjected to, as those are pulled out
      of aggregates, and the enthalpic cost to overcome unfavorable interaction between
      poly(styrene) and mineral oil. Our results provide further insights to the
      failure behavior of the self-assembled TPEGs.

PMID- 30113615
TI  - A series of 3D lanthanide coordination polymers decorated with a rigid 3,5
      pyridinedicarboxylic acid linker: syntheses, structural diversity, DFT study,
      Hirshfeld surface analysis, luminescence and magnetic properties.
AB  - Single crystal X-ray diffraction studies reveal the formation of six new
      coordination polymers (CPs) with the general formulas [Dy(3,5-pdc)(3,5
      pdcH)(H2O)2]n.nH2O (1), [Pr2(3,5-pdc)3(H2O)2]n.2n(H2O) (2), [Sm2(3,5
      pdc)3(H2O)3]n.nH2O (3), {[Eu2(3,5-pdc)3(H2O)3(CH3CHO)]n.n[2(H2O)(DMF)]} (4),
      {[Gd2(3,5-pdc)3 (H2O)2]n.2nH2O} (5) and [Er(3,5-pdc)(adip)0.5(H2O)]n (6) (where
      3,5-pdc2- = fully deprotonated; 3,5-pdcH- = partially deprotonated 3,5
      pyridinedicarboxylic acid; adip2- = fully deprotonated adipic acid; and DMF =
      dimethylformamide) by solvothermal self-assembly of lanthanide ions with rigid
      3,5-pyridinedicarboxylic acid as a linker and adipic acid as an auxiliary
      flexible spacer (only coordinated in CP 6). CPs 1 and 2 crystallize in the
      triclinic P1[combining macron] space group, whereas CPs 3, 4 and 6 crystallize in
      the monoclinic P21/n, P21/c and C2/c space groups, respectively. CP 5 exhibits
      the trigonal R3 space group. The 3,5-pdc ligand exhibits eight diverse
      coordination modes in CPs 1-6, whereas the adipic acid spacer in CP 6 shows only
      one coordination mode (MU4-kappaO:kappaO,O:kappaO:kappaO,O). The organic ligands
      interconnect with metal ions to generate 3D metal-organic frameworks with a
      variety of intriguing topologies. Theoretical studies, DFT calculations and
      Hirshfeld surface analysis support the structures adopted by the various CPs. CPs
      3 (Sm) and 4 (Eu) emit strong ligand-sensitized characteristic f-f luminescence.
      Weak ferromagnetic interactions have been studied at low temperatures for CP 1
      and CP 5.

PMID- 30113616
TI  - The effect of the linker size in C2-symmetrical chiral ligands on the self
      assembly formation of luminescent triple-stranded di-metallic Eu(iii) helicates
      in solution.
AB  - Chiral lanthanide-based supramolecular structures have gained significant
      importance in view of their application in imaging, sensing and other functional
      purposes. We have designed chiral C2-symmetrical ligands (L) based on the use of
      two 2,6-pyridine-dicarboxylic-amide moieties (pda), that differ from one another
      by the nature of the diamine spacer groups (from 1,3-phenylenedimethanamine
      (1(S,S), 2(R,R)) and benzene-1,3-diamine (3(S,S), 4(R,R)) to much bulkier 4,4'
      (cyclohexane-1,1-diyl)bis(2,6-dimethylaniline) (5(S,S), 6(R,R))) between these
      two pda units. The self-assembly between L and Eu(iii) ions were investigated in
      CH3CN solution at low concentration whereby the changes in the absorbance,
      fluorescence and Eu(iii)-centred emission spectra allowed us to model the binding
      equilibria occurring in the solution to the presence of [Eu:L2], [Eu2:L2],
      [Eu2:L3] assemblies and reveal their high binding constant values. The self
      assembly in solution were also studied at higher concentration by following the
      changes in the 1H NMR spectra of the ligands upon Eu(iii) addition, as well as by
      using MALDI-MS of the isolated solid state complexes. The chiroptical properties
      of the ligands were used in order to study the structural changes upon self
      assembly between the ligands and Eu(iii) ions using circular dichroism (CD) and
      circularly polarised luminescence (CPL) spectroscopies. The photophysical
      properties of [Eu2:L3] complexes were evaluated in solution and showed a decrease
      of luminescence quantum yield when going from the ligand with smaller (1(S,S)) to
      bulkier (5(S,S)) linker from ~5.8% to ~2.6%. While mass-spectrometry revealed the
      possible formation of trinucler assemblies such as [Eu3:L3] and [Eu3:L2].

PMID- 30113617
TI  - Omics and bioinformatics applied to vaccine development against Borrelia.
AB  - Borrelia burgdorferi is an extracellular spirochete that causes Lyme disease.
      Currently, no effective vaccine is available for humans and animals except for
      dogs. In the present study, an extensive bioinformatics pipeline was established
      to predict new candidates that can be used for vaccine development including
      building the protein-protein interaction network based on orthologues of
      experimentally verified protein-protein interaction networks, elucidation of the
      proteins involved in the immune response, selection of the topologically
      interesting proteins and their prioritization based on their antigenicity.
      Proteomic network analysis yielded an interactome network with 120 nodes with 97
      interactions. Proteins were selected to obtain a subnet containing only the
      borrelial membrane proteins and immune-related host proteins. This strategy
      resulted in the selection of 15 borrelial targets, which were subjected to
      extensive bioinformatics analysis to predict their antigenic properties. Based on
      the strategy applied in this study the proteins encoded by erpX (ErpX proteins,
      UniProt ID: H7C7L6), erpL (ErpL protein, UniProt ID: H7C7M3) and erpY (ErpY
      protein, UniProt ID: Q9S0D9) are suggested as a novel set of vaccine targets to
      control Lyme disease. Moreover, five different tools were used to validate their
      antigenicity regarding B-cells. The combination of all these proteins in a
      vaccine should allow improved protection against Borrelia infection.

PMID- 30113618
TI  - Diastolic Blood Pressure, Not Just Systolic Blood Pressure, Is Related to
      Cerebral Measures in Middle Age: Implications for Prospective Studies.

PMID- 30113619
TI  - Ultrastructural, Molecular and Functional Mapping of GABAergic Synapses on
      Dendritic Spines and Shafts of Neocortical Pyramidal Neurons.
AB  - The location of GABAergic synapses on dendrites is likely key for neuronal
      integration. In particular, inhibitory inputs on dendritic spines could serve to
      selectively veto or modulate individual excitatory inputs, greatly expanding the
      computational power of individual neurons. To investigate this, we have
      undertaken a combined functional, molecular, and ultrastructural mapping of the
      location of GABAergic inputs onto dendrites of pyramidal neurons from upper
      layers of juvenile mouse somatosensory cortex. Using two-photon uncaging of GABA,
      intracellular labeling with gerphyrin intrabodies, and focused ion beam milling
      with scanning electron microscopy, we find that most (96-98%) spines lack
      GABAergic synapses, although they still display GABAergic responses, potentially
      due to extrasynaptic GABA receptors. We conclude that GABAergic inputs, in
      practice, contact dendritic shafts and likely control clusters of excitatory
      inputs, defining functional zones on dendrites.

PMID- 30113620
TI  - ISCA1 mutation in a patient with infantile-onset leukodystrophy causes defects in
      mitochondrial [4Fe-4S] proteins.

PMID- 30113621
TI  - Percutaneous treatment of a saccular coronary artery aneurysm using multimodal
      imaging and rapid prototyping.

PMID- 30113622
TI  - Erratum to: Evaluation of masticatory muscle activity in patients with unilateral
      posterior crossbite before and after rapid maxillary expansion.

PMID- 30113624
TI  - Determinants of Uncontrolled Hypertension in the Context of Universal Health
      Coverage in Middle-Income Countries.

PMID- 30113625
TI  - Parasympathetic Response Patterns are Associated with Metabolic Syndrome Among
      Older Women but Not Men.
AB  - Background: Little is known about the role of physiological stress responses in
      metabolic syndrome (MetS). Purpose: To examine whether patterns of autonomic
      response to psychological stress are associated with MetS and whether this
      association is moderated by sex. Methods: 1121 men and women (Mage = 65.3 +/-
      6.77 years) with and without coronary artery disease (CAD) underwent an anger
      recall stressor task. Heart rate and heart-rate variability (HRV; HF, LF/HF) were
      assessed. Clusters of participants showing similar patterns of response across
      baseline, stress, and recovery periods were created using ACECLUS and FASTCLUS in
      SAS. Logistic regressions included clusters and interaction between clusters and
      sex as independent variables, controlling for relevant covariates. ANCOVAs were
      conducted in secondary analyses utilizing a continuous composite representation
      of MetS. Results: Men and women showing greater tonic and phasic HR elevations
      were more likely to meet MetS criteria (OR = 1.45, [95% CI = 1.02-2.07], p =
      .037). HF-HRV cluster interacted significantly with sex (p < .001) to predict
      MetS. In women, those with significant parasympathetic withdrawal to stress and
      poor recovery were more likely to have MetS than women with a more moderate
      response (OR = 2.56, [95% CI = 1.23-5.41], p = .013). Women who displayed stress
      related parasympathetic activation were also at greater risk of MetS (OR = 2.30,
      [95% CI = 1.30-4.07], p = .004). Results using a continuous measure of MetS were
      generally consistent with these findings. Conclusion: Among older participants
      with CAD or other noncardiovascular disease, hyperreactivity to stress was
      associated with greater prevalence of MetS, particularly in women. Consistent
      with emerging literature, women who showed blunting or activation of
      parasympathetic responses to stress were similarly at greater risk.

PMID- 30113627
TI  - Distilled Spirits Overconsumption as the Most Important Factor of Excessive Adult
      Male Mortality in Europe.
AB  - Aims: To explain comprehensively variations in adult male mortality rate in
      Europe, and in particular, high mortality in some East European countries with
      particular focus on specific patterns of alcohol consumption. Short summary: Per
      capita distilled spirits consumption is found to be the strongest determinant of
      the adult male mortality rate in Europe as soon as the unrecorded alcohol
      consumption is taken into account. It turns out to be much stronger than the
      other tested significant determinants such as per capita health expenditures,
      smoking prevalence, consumption of hard drugs and per capita consumption of
      vegetables and fruit. Methods: Ordinary least squares (OLS) multiple regression
      with adult male mortality rate as a dependent variable, and various indicators of
      alcohol and drug consumption as well as logarithm of gross domestic product (GDP)
      per capita, logarithm of total per capita health expenditures, latitude (climatic
      factors), per capita fruit and vegetable consumption, smoking prevalence as
      independent factors. Results: Per capita distilled spirits consumption turns out
      to be the strongest determinant of the adult male mortality rate in Europe as
      soon as the unrecorded alcohol consumption is taken into account. It turns out to
      be much stronger than the other tested significant determinants of the adult male
      mortality rate such as per capita health expenditures, smoking prevalence,
      consumption of hard drugs and per capita consumption of vegetables and fruit.
      Still, higher per capita wine consumption has turned out to be a marginally
      significant determinant of the higher adult male mortality rate in some tests.
      Latitude, beer and soft drug consumption have turned out insignificant in this
      study. Conclusions: Spirits consumption is a major risk factor of adult male
      mortality, with significantly greater impact compared to beer and wine.
      Therefore, reduction in distilled spirits consumption in hard liquor drinking
      areas should be a major target in health policy.

PMID- 30113623
TI  - Genome Analyses of the Microalga Picochlorum Provide Insights into the Evolution
      of Thermotolerance in the Green Lineage.
AB  - While the molecular events involved in cell responses to heat stress have been
      extensively studied, our understanding of the genetic basis of basal
      thermotolerance, and particularly its evolution within the green lineage, remains
      limited. Here, we present the 13.3-Mb haploid genome and transcriptomes of a
      halotolerant and thermotolerant unicellular green alga, Picochlorum costavermella
      (Trebouxiophyceae) to investigate the evolution of the genomic basis of
      thermotolerance. Differential gene expression at high and standard temperatures
      revealed that more of the gene families containing up-regulated genes at high
      temperature were recently evolved, and less originated at the ancestor of green
      plants. Inversely, there was an excess of ancient gene families containing
      transcriptionally repressed genes. Interestingly, there is a striking overlap
      between the thermotolerance and halotolerance transcriptional rewiring, as more
      than one-third of the gene families up-regulated at 35  degrees C were also up
      regulated under variable salt concentrations in Picochlorum SE3. Moreover,
      phylogenetic analysis of the 9,304 protein coding genes revealed 26 genes of
      horizontally transferred origin in P. costavermella, of which five were
      differentially expressed at higher temperature. Altogether, these results provide
      new insights about how the genomic basis of adaptation to halo- and
      thermotolerance evolved in the green lineage.

PMID- 30113628
TI  - Critical appraisal of the COMPASS trial.

PMID- 30113626
TI  - Two implantable continuous-flow ventricular assist devices in a biventricular
      configuration: technique and results.
AB  - OBJECTIVES: No continuous-flow right ventricular assist device for long-term
      support is available at the moment. Two continuous-flow ventricular assist
      devices used in a continuous-flow biventricular assist device configuration is an
      emerging option which has proven its feasibility but still is not approved for
      routine use. We present our technique and results of modifying the left
      ventricular assist device and making it suitable for right ventricular support.
      METHODS: Between September 2009 and October 2017, 39 patients received
      implantation of a continuous-flow ventricular assist device for right ventricular
      support in a continuous-flow biventricular assist device configuration. For
      implantation of the HeartWare(r) manufacturers name of the pump HeartWare HVAD
      pump (HVAD)(r) centrifugal ventricular assist device, we performed 2 major
      modifications: banding of the outflow graft and reducing the intracaval length of
      the inflow cannula. The HVAD(r) could be safely implanted into the right atrium
      or ventricle. The HeartMate 3(r) left ventricular assist device needed no
      banding, but we increased the extraventricular part of the inflow cannula.
      RESULTS: The overall 30-day survival for the group receiving primarily a
      continuous-flow biventricular assist device was 72.7% (9.5% standard error of the
      mean (SEM)), and the 1-year survival was 45.0% (10.7% SEM). The overall 30-day
      survival for the group receiving a subsequent pump for right ventricular support
      in a continuous-flow biventricular assist device configuration after temporary
      right ventricular support was 71.4% (12.1% SEM), and 1-year survival was 40.8%
      (13.6% SEM). CONCLUSIONS: At the moment, there is a lack of a continuous-flow
      right ventricular assist device especially designed and approved for right
      ventricular support. Therefore, modifications in continuous-flow ventricular
      assist devices designed for the left ventricle are done to make them suitable for
      right ventricular support. However, more information is needed regarding the
      optimal surgical technique, patient selection and the optimal time point of
      implantation.

PMID- 30113629
TI  - Reply to Dimarakis and Venkateswaran.

PMID- 30113630
TI  - The Cape Town declaration on access to cardiac surgery in the developing world.

PMID- 30113632
TI  - The bicaval Wythenshawe technique in 2018.

PMID- 30113634
TI  - Surgery for arrhythmias and congenital heart disease: is the combined approach
      effective?

PMID- 30113631
TI  - ESMO Consensus Conference on testicular germ cell cancer: diagnosis, treatment
      and follow-up.
AB  - The European Society for Medical Oncology (ESMO) consensus conference on
      testicular cancer was held on 3-5 November 2016 in Paris, France. The conference
      included a multidisciplinary panel of 36 leading experts in the diagnosis and
      treatment of testicular cancer (34 panel members attended the conference; an
      additional two panel members [CB and K-PD] participated in all preparatory work
      and subsequent manuscript development). The aim of the conference was to develop
      detailed recommendations on topics relating to testicular cancer that are not
      covered in detail in the current ESMO Clinical Practice Guidelines (CPGs) and
      where the available level of evidence is insufficient. The main topics identified
      for discussion related to: (1) diagnostic work-up and patient assessment; (2)
      stage I disease; (3) stage II-III disease; (4) post-chemotherapy surgery, salvage
      chemotherapy, salvage and desperation surgery and special topics; and (5)
      survivorship and follow-up schemes. The experts addressed questions relating to
      one of the five topics within five working groups. Relevant scientific literature
      was reviewed in advance. Recommendations were developed by the working groups and
      then presented to the entire panel. A consensus vote was obtained following whole
      panel discussions, and the consensus recommendations were then further developed
      in post-meeting discussions in written form. This manuscript presents the results
      of the expert panel discussions, including the consensus recommendations and a
      summary of evidence supporting each recommendation. All participants approved the
      final manuscript.

PMID- 30113635
TI  - Segmental and tandem chromosome duplications led to divergent evolution of the
      chalcone synthase gene family in Phalaenopsis orchids.
AB  - Background and Aims: Orchidaceae is a large plant family, and its extraordinary
      adaptations may have guaranteed its evolutionary success. Flavonoids are a group
      of secondary metabolites that mediate plant acclimation to challenge
      environments. Chalcone synthase (CHS) catalyses the initial step in the flavonoid
      biosynthetic pathway. This is the first chromosome-level investigation of the CHS
      gene family in Phalaenopsis aphrodite and was conducted to elucidate if
      divergence of this gene family is associated with chromosome evolution. Methods:
      Complete CHS genes were identified from our whole-genome sequencing data sets and
      their gene expression profiles were obtained from our transcriptomic data sets.
      Fluorescence in situ hybridization (FISH) was conducted to position five CHS
      genes to high-resolution pachytene chromosomes. Key Results: The five
      Phalaenopsis CHS genes can be classified into three groups, PaCHS1, PaCHS2 and
      the tandemly arrayed three-gene cluster, which diverged earlier than those of the
      orchid genera and species. Additionally, pachytene chromosome-based FISH mapping
      showed that the three groups of CHS genes are localized on three distinct
      chromosomes. Moreover, an expression analysis of RNA sequencing revealed that the
      five CHS genes had highly differentiated expression patterns and its expression
      pattern-based clustering showed high correlations between sequence divergences
      and chromosomal localizations of the CHS gene family in P. aphrodite.
      Conclusions: Based on their phylogenetic relationships, expression clustering
      analysis and chromosomal distributions of the five paralogous PaCHS genes, we
      proposed that expansion of this gene family in P. aphrodite occurred through
      segmental duplications, followed by tandem duplications. These findings provide
      information for further studies of CHS functions and regulations, and shed light
      on the divergence of an important gene family in orchids.

PMID- 30113633
TI  - The association between blood pressure and long-term outcomes of patients with
      ischaemic cardiomyopathy with and without surgical revascularization: an analysis
      of the STICH trial.
AB  - Aims: Hypertension (HTN) is a well-known contributor to cardiovascular disease,
      including heart failure (HF) and coronary artery disease, and is the leading risk
      factor for premature death world-wide. A J- or U-shaped relationship has been
      suggested between blood pressure (BP) and clinical outcomes in different studies.
      However, there is little information about the significance of BP on the outcomes
      of patients with coronary artery disease and left ventricular dysfunction. This
      study aimed to determine the relationship between BP and mortality outcomes in
      patients with ischaemic cardiomyopathy. Methods and results: The influence of BP
      during a median follow-up of 9.8 years was studied in a total of 1212 patients
      with ejection fraction <=35% and coronary disease amenable to coronary artery
      bypass grafting (CABG) who were randomized to CABG or medical therapy alone (MED)
      in the STICH (Surgical Treatment for Ischaemic Heart Failure) trial. Landmark
      analyses were performed starting at 1, 2, 3, 4, and 5 years after randomization,
      in which previous systolic BP values were averaged and related to subsequent
      mortality through the end of follow-up with a median of 9.8 years. Neither a
      previous history of HTN nor baseline BP had any significant influence on long
      term mortality outcomes, nor did they have a significant interaction with MED or
      CABG treatment. The landmark analyses showed a progressive U-shaped relationship
      that became strongest at 5 years (chi2 and P-values: 7.08, P = 0.069; 8.72, P =
      0.033; 9.86; P = 0.020; 8.31, P = 0.040; 14.52, P = 0.002; at 1, 2, 3, 4, and 5
      year landmark analyses, respectively). The relationship between diastolic BP
      (DBP) and outcomes was similar. The most favourable outcomes were observed in the
      SBP range 120-130, and DBP 75-85 mmHg, whereas lower and higher BP were
      associated with worse outcomes. There were no differences in BP-lowering
      medications between groups. Conclusion: A strong U-shaped relationship between BP
      and mortality outcomes was evident in ischaemic HF patients. The results imply
      that the optimal SBP might be in the range 120-130 mmHg after intervention, and
      possibly be subject to pharmacologic action regarding high BP. Further, low BP
      was a marker of poor outcomes that might require other interactions and treatment
      strategies. Clinical Trial Registration: URL: http://www.clinicaltrials.gov.
      Unique identifier: NCT00023595.

PMID- 30113636
TI  - Successful heart-lung-kidney and domino heart transplantation following veno
      venous extracorporeal membrane oxygenation support.
AB  - A 60-year-old man with cystic fibrosis, mediastinal shift and end-stage kidney
      disease underwent a heart-lung-kidney transplantation. His explanted heart was
      used for a domino heart transplantation. This case showed an excellent outcome,
      even with high preoperative acuity requiring veno-venous extracorporeal membrane
      oxygenation and continuous veno-venous haemodialysis.

PMID- 30113637
TI  - 21st Century Biological Nomenclature-the Enduring Power of Names.
AB  - SYNOPSIS: Nomenclature and taxonomy are complementary and distinct aspects of the
      study of biodiversity, but the two are often confused even by biologists.
      Taxonomy is the part of the science of systematics that deals with identifying,
      describing, and categorizing organisms from species to higher taxa. Nomenclature
      is a system of giving names to organisms based on rules established for the
      process. Adoption of a system of binomial nomenclature by end of the 18th century
      helped standardize the process of naming the wealth of new organisms collected
      during the Age of Exploration, but before the middle of the 19th century, the
      turmoil resulting from differences in procedures and philosophies among
      practicing taxonomists necessitated the development of codes of nomenclature to
      regulate naming. By the early 20th century, codified sets of rules for the names
      of both plants and animals, nowadays usually abbreviated as ICBN (Botanical Code)
      and ICZN (Zoological Code), were in place internationally. These codes worked
      reasonably well through most of the 20th century, under the aegis of various
      international bodies, in part because procedures exist to bypass them when their
      provisions threaten nomenclatural stability. They also inspired the development
      of other nomenclatural codes for specific groups of organisms like bacteria, and,
      alternatively, the proposal of unified codes for all organisms. The rapid
      development of electronic communications and various means of electronic
      publication at the end of the 20th century, combined with what may be the advent
      of a new age of biological extinction, resulted in pressure to revise the codes
      to allow at least some degree of electronic publication and speedier description
      of new taxa in the 21st century. Consistent and unambiguous names are the
      platforms on which biological research and conservation practices are built. As
      we pursue the goals of documenting and conserving biodiversity, for which a
      stable nomenclature is essential, we must do so without restricting the freedom
      of the science of systematics.

PMID- 30113638
TI  - Improved Mental and Motor Development During 3 Years of GH Treatment in Very
      Young Children With Prader-Willi Syndrome.
AB  - Context: Infants and toddlers with Prader-Willi syndrome (PWS) have mental and
      motor developmental delay. Short-term data suggest a positive effect of GH on
      mental and motor development in infants and children with PWS. There are,
      however, no longer-term results about the effects of GH treatment on mental and
      motor development. Objective: To investigate the longer-term effects of GH on
      psychomotor development in infants and toddlers with PWS and the effect of age at
      start of GH treatment on psychomotor development. Design: Prospective cohort
      study during 3 years of GH treatment. Setting: The PWS Reference Center in the
      Netherlands. Intervention: All children were treated with GH 1 mg/m2/d (~0.035
      mg/kg/d). Main Outcome Measures: Mental and motor developmental age assessed with
      Bayleys Scales of Infant Development II and expressed as percentage of the
      expected development (100%). Results: During 3 years of GH, mean (SEM) mental
      development increased from 58.1% (2.8) at baseline to 79.6% (3.7), and motor
      development increased from 41.9% (2.9) to 78.2% (3.9; both P < 0.01). A lower
      baseline psychomotor development and a younger age at start of GH treatment were
      associated with a higher increase in mental and motor development (P < 0.01).
      Conclusions: Mental and motor development increased significantly during 3 years
      of GH treatment, reducing the gap between infants with PWS and healthy peers. A
      younger age at start of GH treatment leads to greater improvement in psychomotor
      development.

PMID- 30113639
TI  - Efficacy of second-line chemotherapy in poor-risk patients with refractory
      relapsed small-cell lung cancer.
AB  - Background: The treatment efficacy of second-line chemotherapy in poor-risk
      patients with refractory-relapsed small-cell lung cancer is unclear. Methods: We
      defined refractory relapse as treatment-free interval <90 days and poor-risk as
      Eastern Cooperative Oncology Group Performance Status >=2. We retrospectively
      examined the medical record data of patients who were treated at our hospital
      between September 2002 and December 2014. Results: Twenty-three poor-risk
      patients with refractory-relapsed small-cell lung cancer were treated in our
      hospital. The characteristics of patients at the time of first-line treatment
      were as follows: median age (range) 71 (57-83) years; male 74%; extensive disease
      96%; proportion of patients with PS 0 or 1 and those with 2-4 was 43 and 57%,
      respectively; median treatment-free interval 26 days. Amrubicin was the most
      commonly used drug and was administered in 15 patients (65%). The overall
      response rate of all patients was 22%. Median progression-free survival and
      overall survival was 2.2 and 3.7 months, respectively. Among patients treated
      with amrubicin, overall response rate was 13%, median progression-free survival
      was 2.2 months, and median overall survival was 3.9 months. The most common grade
      3 or worse adverse events were hematologic toxicities, including leukopenia
      (66%), neutropenia (69%), thrombocytopenia (9%) and anemia (22%). Febrile
      neutropenia was observed in two patients (9%). Conclusions: Second-line
      chemotherapy might have poor efficacy to poor-risk patients with refractory
      relapsed small-cell lung cancer.

PMID- 30113640
TI  - Validation and suggestion of eighth T classifications of the UICC/AJCC staging
      system for nasopharyngeal carcinoma patients: a retrospective analysis.
AB  - Backgrounds: With the aim to validate the applicability of the eighth T
      classifications of AJCC/UICC staging system for nasopharyngeal carcinoma
      patients. Materials and methods: We compare the seventh and eighth T
      classifications of the UICC/AJCC staging system in 382 newly diagnosed
      nasopharyngeal carcinoma patients without cervical lymph node metastasis who were
      staged with magnetic resonance imaging and treated by intensity-modulated
      radiotherapy. Univariate analysis was performed using the log-rank test and
      multivariate analyses with the Cox proportional hazards model were used to
      evaluate the prognostic values between adjacent stage categories. The Akaike
      information criterion and Harrell's concordance index were applied to compare the
      two systems. Results: The median follow-up time was 61.1 months. For local
      relapse-free survival and distant metastasis failure-free survival, the eighth
      editions had superior prognostic value to the seventh edition. The Akaike
      information criterion value was smaller and Harrell's concordance index value was
      larger for the eighth edition compared with the seventh edition staging system.
      Our research also found that the difference in overall survival, local relapse
      free survival and distant metastasis failure-free survival rates between T1 and
      T2 patients was not significant according to the eighth edition of the UICC/AJCC
      staging system, indicating that the discrimination among T1-2 patients was
      diminished. Conclusions: Intensity-modulated radiotherapy with elective neck
      irradiation provides excellent local-regional control for nasopharyngeal
      carcinoma patients and the eighth T classification seems to be superior to the
      seventh T classification. Since local control has improved in the modern era, the
      study considered that the staging system could be further improved and simplified
      by downstaging the current T2 classification patients to T1 with modern
      treatment. Researchers are attempting to incorporate individualized prognostic
      factors, such as Epstein-Barr virus DNA, into nomogram.

PMID- 30113641
TI  - Newborn Screening for Primary Congenital Hypothyroidism: Estimating Test
      Performance at Different TSH Thresholds.
AB  - Context: Active surveillance of primary congenital hypothyroidism (CH) in a
      multiethnic population with established newborn bloodspot screening. Objective:
      To estimate performance of newborn screening for CH at different test thresholds
      and calculate incidence of primary CH. Design: Prospective surveillance from June
      2011 to June 2012 with 3-year follow-up of outcomes. Relative likelihood ratios
      (rLRs) estimated to compare bloodspot TSH test thresholds of 6 mU/L and 8 mU/L,
      with the nationally recommended standard of 10 mU/L for a presumptive positive
      result. Setting: UK National Health Service. Patients: Clinician notification of
      children aged <5 years investigated following clinical presentation or
      presumptive positive screening result. Main Outcome Measure(s): Permanent primary
      CH status determined by clinician report of continuing T4 requirement at 3-year
      follow-up. Results: A total of 629 newborns (58.3% girls; 58.7% white ethnicity)
      were investigated following presumptive positive screening result and 21 children
      (52.4% girls; 52.4% white) after clinical presentation; 432 remained on treatment
      at 3-year follow-up. Permanent CH incidence was 5.3 (95% CI, 4.8 to 5.8) per
      10,000 infants. With use of locally applied thresholds, sensitivity, specificity,
      and positive predictive value were 96.76%, 99.97%, and 66.88%, respectively.
      Compared with a TSH threshold of 10 mU/L, positive rLRs for 8 mU/L and 6 mU/L
      were 1.20 (95% CI, 0.82 to 1.75) and 0.52 (95% CI, 0.38 to 0.72), and negative
      rLRs were 0.11 (95% CI, 0.03 to 0.36) and 0.11 (95% CI, 0.06 to 0.20),
      respectively. Conclusions: Screening program performance is good, but a TSH
      threshold of 8 mU/L appears superior to the current national standard (10 mU/L)
      and requires further evaluation. Further research should explore the implications
      of transient CH for screening policy.

PMID- 30113642
TI  - Comparison of gynecologic cancer risk factors, incidence and mortality trends
      between South Korea and Israel, 1999-2013.
AB  - Objective: To discuss possible causes of disparities in incidence and mortality
      rates of ovarian cancer, uterine cancer and cervical cancer between two diverse
      populations from east and west Asia. Methods: Incidence and mortality data from
      1999 to 2013 were extracted from Korean and Israeli cancer registries. Age
      standardized rates and annual percent changes were calculated. Trends were
      analyzed using Joinpoint analysis and discussed with respect to risk factor
      exposure. Results: Age-standardized rate of ovarian cancer significantly
      increased in Korea (annual percent change 1.7%) but decreased among Jews (annual
      percent change -2.15%). Age-standardized rate of uterine cancer increased among
      both Koreans and Israeli Jews (annual percent changes 5.8 and 1.17%,
      respectively). Incidence of cervical cancer significantly decreased in Korea
      (annual percent change -3.8%) while remained stable on Israel. Mortality trends
      paralleled incidence trends with a significant increase in ovarian cancer and
      uterine cancer mortality in Korea (annual percent changes 1.2 and 4.6%,
      respectively) and a drop in cervical cancer mortality from 2002 (annual percent
      change -5.8%). Among Israeli Jews, uterine cancer mortality increased (annual
      percent change 1.01%), while ovarian cancer mortality decreased (annual percent
      change -0.58%). Uterine cancer mortality among Arabs declined (annual percent
      change -0.5%), while cervical cancer mortality remained unchanged. Conclusions:
      Gynecologic malignancies show different incidence trends in Korea and Israel.
      Uterine cancer is rising in both countries and is correlated to changing trends
      in obesity and dietary habits. Ovarian cancer is rising in Korea but declining
      among Israeli Jews along with changes in parity, childbearing age, contraceptive
      use and increasing awareness to BRCA gene carriers and risk reduction salpingo
      oophorectomy. Cervical cancer is declining in Korea along with an effective
      screening program implemented. Mortality trends follow incidence trends in both
      countries.

PMID- 30113643
TI  - A Pilot Randomized Controlled Trial Testing the Effectiveness of a Pedestrian
      Training Program That Teaches Children Where and How to Cross the Street Safely.
AB  - Objective: Pedestrian injury is a leading cause of injury-related mortality for
      children. This pilot randomized controlled trial tested the efficacy of a
      training program to teach where and how to cross safely. Methods: Using fully
      immersive virtual reality technology, 142 children 7-10 years of age were
      recruited, with 130 completing crossing measures before (pretest) and immediately
      after (posttest) training. Training comprised 1.5 hr, was tailored to each
      child's performance over trials, and focused on either where to cross (n = 44
      children completed testing) or how to cross safely (n = 43); corresponding
      control groups comprised 22 and 21 children, respectively. Following training,
      children in the intervention groups completed additional tasks to test conceptual
      knowledge and generalization of learning. Children in the control groups spent
      the same time as those in training groups but played a video game that used the
      same game controller but provided no training in street crossing. Results: The
      primary outcomes were errors in crossing at posttest, controlling for pretest
      error scores. Children in the intervention group made from 75% to 98% fewer
      errors at posttest than control children for all pedestrian safety variables
      related to where and how to cross safely, with effect sizes (incidence rate
      ratios) varying between 0.02 and 0.25. They also showed a generalization of what
      they had learned and applied this knowledge to novel posttraining situations.
      Conclusion: Training within a virtual pedestrian environment can successfully
      improve children's conceptual understanding and crossing behaviors for both where
      and how to cross streets safely.

PMID- 30113644
TI  - Variability and Determinants of Occupational Noise Exposure Among Iron and Steel
      Factory Workers in Tanzania.
AB  - Background: Machines, processes, and tasks in the iron and steel factories may
      produce noise levels that are harmful to hearing if not properly controlled.
      Studies documenting noise exposure levels and related determinants in sub-Saharan
      Africa, including Tanzania are lacking. The aim of this study was to document
      noise exposure and to identify determinants of noise exposure with a view to
      establishing an effective hearing conservation programme. Methods: A walk-through
      survey was conducted to describe the working environment in terms of noise
      sources in four metal factories (A-D) in Tanzania. Noise measurements were
      conducted by both personal, full-shift noise measurements (8 h) using dosimeters
      and area measurements (10-s measurements) using a sound level meter. A total of
      163 participants had repeated personal noise measurements (Factory A: 46
      participants, B: 43, C: 34, and D: 40). Workers were randomly selected and
      categorized into 13 exposure groups according to their job. Linear mixed effects
      models were used to identify significant determinants of noise exposure in the
      furnace section and the rolling mill section. Results: The average personal noise
      exposure in the four factories was 92.0 dB(A) (range of job group means; 85.4
      96.2 dB(A)) (n = 326). Personal exposure was significantly higher in the rolling
      mill section (93.0 dB(A)) than in the furnace section (89.6 dB(A)). Among the job
      groups, the cutters located in the rolling mill section had the highest noise
      exposure (96.2 dB(A)). In the furnace section, furnace installation (below the
      ground floor), manual handling of raw materials/billets/crowbars, and billet
      weighing/transfer were significant determinants explaining 40% of the total
      variance in personal noise exposure. In the rolling mill section, the size of the
      cutting machine, steel billet weight and feeding re-heating furnace explained 46%
      of the total variance in personal noise exposure. The mean noise level of the
      area measurements was 90.5 dB(A) (n = 376). Conclusion: Workers in the four iron
      and steel factories in Tanzania were exposed to average noise of 92.0 dB(A),
      without using hearing protection, implying a high risk of developing hearing
      loss. Task and factory level determinants were identified in the furnace and the
      rolling mill sections of the plant, which can inform noise control in factories
      with similar characteristics.

PMID- 30113646
TI  - The Association of Acylcarnitines and Amino Acids With Age in Dutch and South
      Asian Surinamese Living in Amsterdam.
AB  - Context: Type 2 diabetes and cardiovascular disease occur more frequently and at
      a younger age in South-Asians than Europeans. This may be related to differences
      in regulation of the fatty acid metabolism during aging. We compared age-related
      acylcarnitine and amino acid concentrations in Dutch and South-Asian Surinamese
      study participants. Methods: We measured types of acylcarnitine and amino acid
      concentrations in plasma (by tandem mass spectrometry) in a random subsample of
      350 Dutch and 350 South-Asian Surinamese origin participants of the Healthy Life
      in an Urban Setting study (Amsterdam, Netherlands). We derived principal
      components (PCs) from the metabolites. Linear regression was used to assess
      differences in PCs and individual metabolite concentrations, and their age trends
      between the groups by sex. We adjusted for body mass index and intake of fat and
      total energy. Results: Mean age was 44.8 (SD, 13.3) years. Amino acid
      concentrations were higher among South-Asian Surinamese women compared with Dutch
      women; acylcarnitine and amino acid levels were higher among South-Asian
      Surinamese men than Dutch men. Metabolite levels increased similarly with age in
      both ethnic groups. Results remained similar after adjustment. Conclusion: Ethnic
      differences in metabolite concentrations suggest that fatty acid and amino acid
      metabolism are more dysregulated among South-Asian Surinamese compared with Dutch
      from a young age. During adulthood, metabolites increase similarly in both ethnic
      groups.

PMID- 30113647
TI  - Cardiometabolic Biomarkers and Their Temporal Patterns Predict Poor Outcome in
      Chronic Heart Failure (Bio-SHiFT Study).
AB  - Purpose: Multiple hormonal and metabolic alterations occur in chronic heart
      failure (CHF), but their proper monitoring during clinically silent progression
      of CHF remains challenging. Hence, our objective was to explore whether temporal
      patterns of six emerging cardiometabolic biomarkers predict future adverse
      clinical events in stable patients with CHF. Methods: In 263 patients with CHF,
      we determined the risk of a composite end point of heart failure hospitalization,
      cardiac death, left ventricular assist device implantation, and heart
      transplantation in relation to serially assessed blood biomarker levels and
      slopes (i.e., rate of biomarker change per year). During 2.2 years of follow-up,
      we repeatedly measured IGF binding proteins 1, 2, and 7 (IGFBP-1, IGFBP-2, IGFBP
      7), adipose fatty acid binding protein 4 (FABP-4), resistin, and chemerin (567
      samples in total). Results: Serially measured IGFBP-1, IGFBP-2, IGFBP-7, and FABP
      4 levels predicted the end point [univariable hazard ratio (95% CI) per 1-SD
      increase: 3.34 (2.43 to 4.87), 2.86 (2.10 to 3.92), 2.45 (1.91 to 3.13), and 2.46
      (1.88 to 3.24), respectively]. Independently of the biomarkers' levels, their
      slopes were also strong clinical predictors [per 0.1-SD increase: 1.20 (1.11 to
      1.31), 1.27 (1.14 to 1.45), 1.23 (1.11 to 1.37), and 1.27 (1.12 to 1.48)]. All
      associations persisted after multivariable adjustment for patient baseline
      characteristics, baseline N-terminal pro-hormone brain natriuretic peptide and
      cardiac troponin T, and pharmacological treatment during follow-up. Main
      Conclusions: The temporal patterns of IGFBP-1, IGFBP-2, IGFBP-7, and adipose FABP
      4 predict adverse clinical outcomes during outpatient follow-up of patients with
      CHF and may be clinically relevant as they could help detect more aggressive CHF
      forms and assess patient prognosis, as well as ultimately aid in designing more
      effective biomarker-guided therapy.

PMID- 30113645
TI  - Sex Differences in the Prenatal Programming of Adult Metabolic Syndrome by
      Maternal Androgens.
AB  - Context: Growing preclinical evidence suggests that hormonal programming by
      androgens in utero may contribute to cardiovascular disease risk in adult
      offspring. However, the effect of prenatal androgens on cardiometabolic outcomes
      in the human population, especially their potential differential impact on male
      vs female offspring, has not been well studied. Design: Adult offspring (n = 274)
      of mothers enrolled in the New England birth cohorts of the Collaborative
      Perinatal Project were assessed at ages 39 to 50. Androgen bioactivity was
      measured in maternal serum during the third trimester using a receptor-mediated
      luciferase expression bioassay. Metabolic syndrome (MetS) using Adult Treatment
      Panel III criteria was assessed in adult offspring. Bioactive androgens were
      analyzed as quartiles, with the lowest quartile (Q1) defined as the reference.
      Generalized estimating equations were used to evaluate the relationship of
      maternal bioactive androgens on offspring MetS risk overall and by sex,
      controlling for potential confounders and intrafamilial correlation. Results:
      Mean age and body mass index of adult offspring were 44.7 +/- 2.6 years and 29.7
      +/- 6.7 kg/m2, respectively. Participants born to mothers with the highest
      quartile (Q4) compared with Q1 of bioactive androgens had higher risk for MetS
      [adjusted odds ratio (aOR): 2.53(1.07 to 6.02)]. Stratified by sex, this
      association was found to be significant among women [Q4 vs Q1; aOR: 4.06 (1.10 to
      14.93)] but not men [Q4 vs Q1; aOR: 1.67 (0.53 to 5.26)]. Women born to mothers
      with the highest levels of maternal bioactive androgens also demonstrated a 4.84
      fold increased odds for having hypertension [Q4 vs Q1; aOR: 4.84 (1.12 to
      20.85)]. Conclusion: Higher levels of maternal androgens were associated with
      increased risk for incident MetS in adult offspring, an effect that was
      significant in women but not men.

PMID- 30113648
TI  - Endocannabinoid Anandamide Mediates the Effect of Skeletal Muscle Sphingomyelins
      on Human Energy Expenditure.
AB  - Context: Skeletal muscle endocannabinoids and sphingolipids (particularly
      sphingomyelins) are inversely associated with sleeping energy expenditure (SLEEP)
      in humans. The endocannabinoid system may increase sphingolipid synthesis via
      cannabinoid receptor-1. Objective: To investigate in human skeletal muscle
      whether endocannabinoids are responsible for the effect of sphingomyelins on
      SLEEP. Design: Muscle endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol
      (2-AG)], endocannabinoid congeners [oleoylethanolamide (OEA),
      palmitoylethanolamide (PEA)], and sphingomyelin content were measured with liquid
      chromatography/mass spectrometry. SLEEP was assessed in a whole-room indirect
      calorimeter. Mediation analyses tested whether the inverse associations between
      sphingomyelins and SLEEP depended on endocannabinoids and endocannabinoid-related
      OEA and PEA. Setting: Inpatient study. Participants: Fifty-three Native Americans
      who are overweight. Main Outcome Measure: SLEEP. Results: AEA (r = 0.45, P =
      0.001), 2-AG (r = 0.47, P = 0.0004), OEA (r = 0.27, P = 0.05), and PEA (r = 0.53,
      P < 0.0001) concentrations were associated with the total sphingomyelin content.
      AEA, OEA, and PEA correlated with specific sphingomyelins (SM18:1/23:0,
      SM18:1/23:1, and SM18:1/26:1) previously reported to be determinants of SLEEP in
      Native Americans (all r > 0.31, all P < 0.03). Up to half of the negative effect
      of these specific sphingomyelins on SLEEP was accounted for by AEA (all P <
      0.04), rendering the direct effect by sphingomyelins per se on SLEEP negligible
      (P > 0.05). Conclusions: In skeletal muscle, AEA is responsible for the
      sphingomyelin effect on SLEEP, indicating that endocannabinoids and
      sphingomyelins may jointly reduce human whole-body energy metabolism.

PMID- 30113649
TI  - Pheochromocytoma in Children and Adolescents With Multiple Endocrine Neoplasia
      Type 2B.
AB  - Context: Multiple endocrine neoplasia type 2B (MEN2B) is characterized by early
      onset medullary thyroid cancer in virtually all cases and a 50% lifetime risk of
      pheochromocytoma (PHEO) development. The literature on PHEO in patients with
      MEN2B is limited with most data being reported from adult studies that primarily
      address MEN2A. Objective: The aim of the current study is to describe PHEO
      development in a cohort of pediatric patients with MEN2B. Design: Retrospective
      chart review of patients with MEN2B evaluated at the National Institutes of
      Health in the period between July 2007 and February 2018. Results: A total of 38
      patients were identified (21 males and 17 females). Mean age at MEN2B diagnosis
      was 10.6 +/- 3.9 years. Eight patients (21%) developed PHEO in the course of
      follow-up to date, all of whom were sporadic cases with the classic M918T RET
      mutation. PHEO was diagnosed based on biochemical and/or imaging screening
      studies in five patients, whereas three patients presented with symptoms of
      excess catecholamines. PHEO was diagnosed at a mean age 15.2 +/- 4.6 (range, 10
      to 25) years and 4.0 +/- 3.3 years after MEN2B diagnosis. Only one patient was
      diagnosed with PHEO as the initial manifestation of MEN2B after she presented
      with hypertension and secondary amenorrhea. Conclusion: Undiagnosed PHEO can be
      associated with substantial morbidity. Current American Thyroid Association
      guidelines recommend PHEO screening starting at age 11 for the high-/highest risk
      group. The youngest patient diagnosed with PHEO in our cohort was an asymptomatic
      10-year-old, suggesting that PHEO development may begin before the screening
      recommended age of 11, though remains clinically undetectable and thus the
      current screening guidelines seem appropriate.

PMID- 30113650
TI  - Early-Onset Complete Ovarian Failure and Lack of Puberty in a Woman With Mutated
      Estrogen Receptor beta (ESR2).
AB  - Context: Estrogen resistance due to mutations in the estrogen receptor alpha gene
      (ESR1) has been described in men and women and is characterized by osteoporosis,
      delayed bone age and continuous growth in adulthood, and delayed puberty and
      multiple ovarian cysts in women. Although mutations in the estrogen receptor beta
      gene ESR2 were found in 46, XY patients with differences of sex development, no
      genetic variants of ESR2 were linked to gonadal defects in women. Settings and
      Patient: Here we describe a 16-year-old female patient who came to our tertiary
      care hospital with complete lack of estrogen action, as demonstrated by absent
      breast development, primary amenorrhea, and osteoporosis, resembling patients
      with ESR1 mutation. However, her gonads were clearly abnormal (streak), a finding
      not observed in ESR1-deficient patients. Design: To gain insights into the
      molecular consequences of the ESR2 defect, whole exome sequencing and extensive
      functional transactivation studies in ovarian, bone, and breast cells were
      conducted, with or without the natural activator of estrogen receptors, 17beta
      estradiol. Results: We identified a loss-of-function heterozygous mutation of a
      highly conserved residue in ESR2 that disrupts estradiol-dependent signaling and
      has a dominant negative effect, most likely due to failure to interact with its
      coactivator, nuclear coactivator 1. Conclusions: This is a report of a loss-of
      function mutation in the estrogen receptor beta in a young woman with complete
      ovarian failure, suggesting that ESR2 is necessary for human ovarian
      determination and/or maintenance and that ESR1 is not sufficient to sustain
      ovarian function in humans.

PMID- 30113651
TI  - Effects of SGLT2 Inhibitors on Circulating Stem and Progenitor Cells in Patients
      With Type 2 Diabetes.
AB  - Context: Reduction in the levels of circulating stem cells (CSCs) and endothelial
      progenitor cells (EPCs) predicts development or progression of microangiopathy
      and macroangiopathy in patients with type 2 diabetes (T2D). Objective: We tested
      whether treatment with sodium glucose cotransporter-2 (SGLT2) inhibitors affected
      the levels of CSCs and EPCs. Design: A randomized trial of dapagliflozin vs
      placebo with open-label extension, and an open-label observational study of
      empagliflozin treatment. Setting: Tertiary referral diabetes outpatient clinic.
      Patients: Patients with T2D aged 18 to 75 years. Intervention: Dapagliflozin at
      10 mg vs placebo (n = 31); empagliflozin at 10 mg (n = 15). Main Outcome
      Measures: We measured CSCs (CD34+) and EPCs (CD34+KDR+) by flow cytometry at
      baseline, at 12 weeks, and after the extension period. Results: After 12 weeks,
      CSCs declined nonsignificantly in the dapagliflozin group, remained stable in the
      placebo group, and the change from baseline was not significantly different
      between the two groups. EPCs declined nonsignificantly in the dapagliflozin
      group, increased nonsignificantly in the placebo group, and the change from
      baseline was significantly different between the two groups. After an open-label
      extension period of about 1.5 years, CSCs remained stable over time, whereas EPCs
      significantly increased in patients who received dapagliflozin. In all patients,
      irrespectively of treatment, EPCs increased significantly from baseline to the
      end of observation, concomitantly with improvement in HbA1c. In a cohort of 15
      patients who received open-label empagliflozin for 12 weeks, CSCs declined
      nonsignificantly, whereas EPCs remained stable. Conclusion: SGLT2 inhibitors do
      not significantly increase CSCs or EPCs. Thus, cardiovascular protection by SGLT2
      inhibitors may not directly involve stem/progenitor cells.

PMID- 30113652
TI  - Vascular Endothelial FSH Receptor, a Target of Interest for Cancer Therapy.
AB  - Improved molecular understanding of tumor microenvironment has resulted in the
      identification of various cancer cell targets for diagnostic and therapeutic
      interventions, including the receptor for the FSH, a glycoprotein hormone
      responsible for growth, maturation, and function of human reproductive system.
      The expression and localization of the FSH receptor (FSHR)-protein were
      associated with the tumor epithelial cells and/or with the peripheral tumor blood
      vessels. The available evidence indicates that in ovarian cancer, prostate
      cancer, and breast cancer, the tumor epithelial FSHR promotes proliferation,
      migration, and invasion of cancer cells. The vascular endothelial FSHR, detected
      in 11 types of solid tumors and 11 types of sarcomas, is involved in receptor
      mediated transendothelial transport of FSH, tumor angiogenesis, and vascular
      remodeling. In contrast to intratumor vessels, which are abnormal and
      disorganized, the FSHR-positive blood microvessels are arranged in a hierarchical
      pattern: arterioles-capillaries-venules. The FSHR-positive blood vessels make
      connections between the intratumor vessels and the general blood circulation of
      patients. In this mini-review, I summarize these studies and discuss the
      rationale for developing a strategy for cancer therapy based on FSHR expressed on
      the luminal endothelial cell surface of blood vessels located in the peritumoral
      area rather than endothelial markers expressed in the core of tumors. Because
      FSHR is a common marker of peritumoral vessels, therapeutic agents coupled to
      anti-FSHR humanized antibodies should in principle be applicable to a wide range
      of tumor types.

PMID- 30113654
TI  - A 'fluttering' diastolic murmur.

PMID- 30113653
TI  - Durable response after discontinuation of nivolumab therapy in patients with
      metastatic renal cell carcinoma.
AB  - We investigated the efficacy of nivolumab treatment in patients with metastatic
      renal cell carcinoma who discontinued nivolumab treatment due to reasons other
      than disease progression. Of the 34 patients, 3 patients discontinued nivolumab
      therapy due to adverse events and were subsequently observed without additional
      treatment. The first patient discontinued nivolumab after 14 cycles of treatment
      due to type 1 diabetes mellitus and has maintained partial remission for 8
      months. The second patient discontinued nivolumab after 11 cycles of treatment
      due to interstitial pneumonitis, and durable response was confirmed for 5 months.
      However, multiple lung lesions reappeared at 6 months after discontinuing
      nivolumab. The third patient discontinued nivolumab due to elevated liver enzymes
      after three cycles of treatment. At the time of discontinuation, a new liver
      lesion appeared, but the lesion decreased in size at 6 months after
      discontinuation. In the present study, a relatively durable response was observed
      in three patients who discontinued nivolumab without additional treatment.

PMID- 30113655
TI  - Macrophage Infiltration in the Saccular Intracranial Aneurysm Wall as a Response
      to Locally Lysed Erythrocytes That Promote Degeneration.
AB  - Saccular intracranial aneurysm (sIA) rupture is often fatal. Rupture-prone sIA
      walls are infiltrated by macrophages expressing hemoglobin-receptor CD163,
      suggesting a role for erythrocyte lysis in the degenerative remodeling
      predisposing to rupture. We therefore studied erythrocyte remnants in 16
      unruptured and 20 ruptured sIA walls using histology and immunohistochemistry.
      Glycophorin A (GPA), an erythrocyte membrane protein, was present in 34/36 (94%)
      sIA walls and correlated with loss of alphaSMA+ cells, reflecting loss of mural
      smooth muscle cells ([SMCs]; r = -0.592, p < 0.001), wall degeneration (p =
      0.008), and rupture (p = 0.005). GPA correlated with high numbers of CD163+ and
      CD68+ phagocytes (r = 0.65 and r = 0.54, p <= 0.001 for both). CD163+ phagocytes
      were mostly HLA-DR-. Interestingly, single SMCs expressed HLA-DR and also CD163
      was expressed in sporadic SMCs, which may reflect their response to hemoglobin
      accumulation. GPA associated with iron (p = 0.014) was detectable by MRI. An
      additional 11 sIAs were therefore imaged ex vivo with a 4.7 T MRI prior to
      histology. In the sIA walls, high GPA and iron accumulation associated with
      signal intensity in T1-weighted gradient echo MRI. We conclude that accumulation
      of lysed erythrocytes is a potential driver of inflammatory response in the sIA
      walls and is associated with the degenerative wall remodeling, thereby
      predisposing to rupture.

PMID- 30113656
TI  - Targeted Molecular Analysis in Adrenocortical Carcinomas: A Strategy Toward
      Improved Personalized Prognostication.
AB  - Context: Adrenocortical carcinoma (ACC) has a heterogeneous prognosis, and
      current medical therapies have limited efficacy in its advanced stages. Genome
      wide multiomics studies identified molecular patterns associated with clinical
      outcome. Objective: Here, we aimed at identifying a molecular signature useful
      for both personalized prognostic stratification and druggable targets, using
      methods applicable in clinical routine. Design: In total, 117 tumor samples from
      107 patients with ACC were analyzed. Targeted next-generation sequencing of 160
      genes and pyrosequencing of 4 genes were applied to formalin-fixed, paraffin
      embedded (FFPE) specimens to detect point mutations, copy number alterations, and
      promoter region methylation. Molecular results were combined with
      clinical/histopathological parameters (tumor stage, age, symptoms, resection
      status, and Ki-67) to predict progression-free survival (PFS). Results: In
      addition to known driver mutations, we detected recurrent alterations in genes
      not previously associated with ACC (e.g., NOTCH1, CIC, KDM6A, BRCA1, BRCA2). Best
      prediction of PFS was obtained integrating molecular results (more than one
      somatic mutation, alterations in Wnt/beta-catenin and p53 pathways, high
      methylation pattern) and clinical/histopathological parameters into a combined
      score (P < 0.0001, chi2 = 68.6). Accuracy of prediction for early disease
      progress was 83.3% (area under the receiver operating characteristic curve:
      0.872, 95% confidence interval 0.80 to 0.94). Furthermore, 17 potentially
      targetable alterations were found in 64 patients (e.g., in CDK4, NOTCH1, NF1,
      MDM2, and EGFR and in DNA repair system). Conclusions: This study demonstrates
      that molecular profiling of FFPE tumor samples improves prognostication of ACC
      beyond clinical/histopathological parameters and identifies new potential drug
      targets. These findings pave the way to precision medicine in this rare disease.

PMID- 30113657
TI  - Vegetation Cover and Microspatial Distribution of Sand Flies (Diptera:
      Psychodidae) in an Endemic Locality for Cutaneous Leishmaniasis in Northern
      Argentina.
AB  - The sand fly fauna in Hipolito Yrigoyen, Argentina, a locality where cutaneous
      leishmaniasis cases occur, was surveyed with zones of higher abundance of sand
      flies correlated to vegetation cover estimated through normalized difference
      vegetation index (NDVI). Sand flies were collected with 10 CDC traps during six
      nights, from December 2009 to January 2010. A map was built of expected sand
      flies abundance in which levels of NDVI were categorized. In total, 1,392
      Phlebotominae (Diptera: Psychodidae) specimens were collected, comprised of the
      following species: Nyssomyia neivai (Pinto 1926), Migonemyia migonei (Franca
      1920), species of the cortelezzii complex (Brethes 1923), Evandromyia sallesi
      (Galvao & Coutinho 1940), and Psathyromyia shannoni (Dyar 1929). Positive
      correlations were found between the abundance of sand flies and the NDVI (P <
      0.05) for buffer areas of <150 m radii from the trap location points, i.e., the
      sand fly abundance was greater where vegetation cover and density were greater.
      In this context, plant cover should be taken into account to prioritize
      surveillance and control areas within the program of sand flies control in
      northern Argentina.

PMID- 30113659
TI  - Blood Metabolomic Measures Associate With Present and Future Glycemic Control in
      Type 2 Diabetes.
AB  - Objective: We studied whether blood metabolomic measures in people with type 2
      diabetes (T2D) are associated with insufficient glycemic control and whether this
      association is influenced differentially by various diabetes drugs. We then
      tested whether the same metabolomic profiles were associated with the initiation
      of insulin therapy. Methods: A total of 162 metabolomic measures were analyzed
      using a nuclear magnetic resonance-based method in people with T2D from four
      cohort studies (n = 2641) and one replication cohort (n = 395). Linear and
      logistic regression analyses with adjustment for potential confounders, followed
      by meta-analyses, were performed to analyze associations with hemoglobin A1c
      levels, six glucose-lowering drug categories, and insulin initiation during a 7
      year follow-up period (n = 698). Results: After Bonferroni correction, 26
      measures were associated with insufficient glycemic control (HbA1c >53 mmol/mol).
      The strongest association was with glutamine (OR, 0.66; 95% CI, 0.61 to 0.73; P =
      7.6 * 10-19). In addition, compared with treatment-naive patients, 31 metabolomic
      measures were associated with glucose-lowering drug use (representing various
      metabolite categories; P <= 3.1 * 10-4 for all). In drug-stratified analyses,
      associations with insufficient glycemic control were only mildly affected by
      different glucose-lowering drugs. Five of the 26 metabolomic measures
      (apolipoprotein A1 and medium high-density lipoprotein subclasses) were also
      associated with insulin initiation during follow-up in both discovery and
      replication. The strongest association was observed for medium high-density
      lipoprotein cholesteryl ester (OR, 0.54; 95% CI, 0.42 to 0.71; P = 4.5 * 10-6).
      Conclusion: Blood metabolomic measures were associated with present and future
      glycemic control and might thus provide relevant cues to identify those at
      increased risk of treatment failure.

PMID- 30113660
TI  - Engaging Families in Rehabilitation of People Who Are Critically Ill: An
      Underutilized Resource.
AB  - Rehabilitation of people who are critically ill has received increased attention
      in recent years, although this has not extended to specifically facilitating
      family involvement. Engaging families in the rehabilitation arc has the potential
      to optimize outcomes. Likely benefits include redirecting family psychological
      distress into an active participatory role, humanizing the patient illness and
      recovery experience, and supporting staff and the health care system beyond the
      constraints of therapy time. This viewpoint explores why families should be
      engaged in critical care rehabilitation, gives an overview of the evidence for
      family participation in bedside care, and provides practical implementation
      strategies and signpost areas for future research.

PMID- 30113658
TI  - INFERNO: inferring the molecular mechanisms of noncoding genetic variants.
AB  - The majority of variants identified by genome-wide association studies (GWAS)
      reside in the noncoding genome, affecting regulatory elements including
      transcriptional enhancers. However, characterizing their effects requires the
      integration of GWAS results with context-specific regulatory activity and linkage
      disequilibrium annotations to identify causal variants underlying noncoding
      association signals and the regulatory elements, tissue contexts, and target
      genes they affect. We propose INFERNO, a novel method which integrates hundreds
      of functional genomics datasets spanning enhancer activity, transcription factor
      binding sites, and expression quantitative trait loci with GWAS summary
      statistics. INFERNO includes novel statistical methods to quantify empirical
      enrichments of tissue-specific enhancer overlap and to identify co-regulatory
      networks of dysregulated long noncoding RNAs (lncRNAs). We applied INFERNO to two
      large GWAS studies. For schizophrenia (36,989 cases, 113,075 controls), INFERNO
      identified putatively causal variants affecting brain enhancers for known
      schizophrenia-related genes. For inflammatory bowel disease (IBD) (12,882 cases,
      21,770 controls), INFERNO found enrichments of immune and digestive enhancers and
      lncRNAs involved in regulation of the adaptive immune response. In summary,
      INFERNO comprehensively infers the molecular mechanisms of causal noncoding
      variants, providing a sensitive hypothesis generation method for post-GWAS
      analysis. The software is available as an open source pipeline and a web server.

PMID- 30113661
TI  - Prebiotic and probiotic treatment of nonalcoholic fatty liver disease: a
      systematic review and meta-analysis.
AB  - Context: Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent and
      underdiagnosed comorbidity of many chronic diseases that is associated with
      altered intestinal bacterial communities. This association has prompted research
      into alternative treatments aimed at modulating intestinal microbiota. Given the
      novelty of these treatments, scarce evidence regarding their effectiveness in
      clinical populations exists. Objective: This meta-analysis sought to systemically
      review and quantitatively synthesize evidence on prebiotic, probiotic, and
      synbiotic therapies for patients with NAFLD in randomized controlled trials. Data
      sources: PRISMA guidelines ensured transparent reporting of evidence. PICOS
      criteria defined the research question for the systematic review. A systematic
      keyword search in PubMed and EMBASE identified 25 studies: 9 assessed prebiotic,
      11 assessed probiotic, and 7 assessed symbiotic therapies for a total of 1309
      patients. Data extraction: Basic population characteristics, the primary
      variables of aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      (utilized for NAFLD diagnosis), and the secondary variables of body mass index
      (BMI), gamma-glutamyl transferase (gamma-GT), tumor necrosis factor alpha (TNF
      alpha), C-reactive protein (CRP), total cholesterol, high-density lipoprotein
      cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and
      triglyceridges (TAG) were extracted. Pooled effect sizes of these variables were
      calculated by meta-analysis. No publication bias was identified using Begg's and
      Egger's tests or Cochrane bias assessment tool. Results: Meta-analysis indicated
      that microbial therapies significantly reduced BMI (-0.37 kg/m2; 95% confidence
      interval [CI], -0.46 to -0.28; P < 0.001), hepatic enzymes (ALT, -6.9 U/L [95%CI,
      -9.4 to -4.3]; AST, -4.6 U/L [95%CI, -6.6 to -2.7]; gamma-GT, -7.9 U/L [95%CI, 
      11.4 to -4.4]; P < 0.001), serum cholesterol (-10.1 mg/dL 95%CI, -13.6 to -6.6; P
      < 0.001), LDL-c (-4.5 mg/dL; 95%CI, -8.9 to -0.17; P < 0.001), and TAG (-10.1
      mg/dL; 95%CI, -18.0 to -2.3; P < 0.001), but not inflammation (TNF-alpha, -2.0
      ng/mL; [95%CI, -4.7 to 0.61]; CRP, -0.74 mg/L [95%CI, -1.9 to 0.37]). Subgroup
      analysis by treatment category indicated similar effects of prebiotics and
      probiotics on BMI and liver enzymes but not total cholesterol, HDL-c, and LDL-c.
      Conclusion: This meta-analysis supports the potential use of microbial therapies
      in the treatment of NAFLD and sheds light on their potential mode of action.
      Further research into these treatments should consider the limitations of
      biomarkers currently used for the diagnosis and progression of NAFLD, in addition
      to the inherent challenges of personalized microbial-based therapies.

PMID- 30113662
TI  - Moving Beyond Collaboration: A Model for Enhancing Social Work's Organizational
      Empathy.
AB  - Many first-year field students and new practitioners enter the "fog of practice"
      seeking a strong mentor who will teach them to survive and thrive in the practice
      world. They are armed with much social work-related ideology but perhaps too
      little organizational knowledge and savvy. This challenge may be traced back to
      another historical professional debate: the imbalance between micro and macro
      social work education and training. This article addresses the challenge by
      introducing the overarching competency of organizational empathy, defined as an
      understanding of the practice environment one occupies. The major objective of
      this article is to help bridge an academe-practice knowledge gap, thereby giving
      the social work practitioner enhanced opportunities for broader organizational
      influence, collaboration, and leadership.

PMID- 30113664
TI  - Postoperative Rigid Cervical Collar Leads to Less Axial Neck Pain in the Early
      Stage After Open-Door Laminoplasty-A Single-Blinded Randomized Controlled Trial.
AB  - BACKGROUND: Cervical collars are used after laminoplasty to protect the hinge
      opening, reduce risks of hinge fractures, and avoid spring-back phenomena.
      However, their use may lead to reduced range of motion and worse neck pain.
      OBJECTIVE: To investigate the clinical, radiological, and functional outcomes of
      patients undergoing single-door laminoplasty with or without collar
      immobilization. METHODS: This was a prospective, parallel, single-blinded
      randomized controlled trial. Patients underwent standardized single-door
      laminoplasty with mini-plates for cervical myelopathy and were randomly allocated
      into 2 groups based on the use of collar postoperatively. Clinical assessments
      included cervical range of motion, axial neck pain (VAS [visual analogue scale]),
      and objective scores (short-form 36-item, neck disability index, and modified
      Japanese Orthopaedic Association). All assessments were performed preoperatively
      and at postoperative 1, 2, 3, and 6 wk, and 3, 6, and 12 mo. Comparative analysis
      was performed via analysis of variance adjusted by baseline scores, sex, and age
      as covariates. RESULTS: A total of 35 patients were recruited and randomized to
      collar use (n = 16) and without (n = 19). There were no dropouts or
      complications. There were no differences between groups at baseline. Subjects had
      comparable objective scores and range of motion at postoperative time-points.
      Patients without collar use had higher VAS at postoperative 1 wk (5.4 vs 3.5; P =
      .038) and 2 wk (3.5 vs 1.5; P = .028) but subsequently follow-up revealed no
      differences between the 2 groups. CONCLUSION: The use of a rigid collar after
      laminoplasty leads to less axial neck pain in the first 2 wk after surgery.
      However, there is no additional benefit with regards to range of motion, quality
      of life, and complication risk.

PMID- 30113663
TI  - Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in
      Women With Polycystic Ovary Syndrome.
AB  - Context: Insulin resistance in skeletal muscle is a major risk factor for the
      development of type 2 diabetes in women with polycystic ovary syndrome (PCOS).
      Despite this, the mechanisms underlying insulin resistance in PCOS are largely
      unknown. Objective: To investigate the genome-wide DNA methylation and gene
      expression patterns in skeletal muscle from women with PCOS and controls and
      relate them to phenotypic variations. Design/Participants: In a case-control
      study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-,
      and body mass index-matched controls (n = 14) were analyzed by array-based DNA
      methylation and mRNA expression profiling. Results: Eighty-five unique
      transcripts were differentially expressed in muscle from women with PCOS vs
      controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS
      had reduced expression of genes involved in immune system pathways. Two CpG sites
      showed differential DNA methylation after correction for multiple testing.
      However, an mRNA expression of ~30% of the differentially expressed genes
      correlated with DNA methylation levels of CpG sites in or near the gene.
      Functional follow-up studies demonstrated that KLF10 is under transcriptional
      control of insulin, where insulin promotes glycogen accumulation in myotubes of
      human muscle cells. Testosterone downregulates the expression levels of COL1A1
      and MAP2K6. Conclusion: PCOS is associated with aberrant skeletal muscle gene
      expression with dysregulated pathways. Furthermore, we identified specific
      changes in muscle DNA methylation that may affect gene expression. This study
      showed that women with PCOS have epigenetic and transcriptional changes in
      skeletal muscle that, in part, can explain the metabolic abnormalities seen in
      these women.

PMID- 30113665
TI  - Predicting Inpatient Length of Stay After Brain Tumor Surgery: Developing Machine
      Learning Ensembles to Improve Predictive Performance.
AB  - BACKGROUND: Current outcomes prediction tools are largely based on and limited by
      regression methods. Utilization of machine learning (ML) methods that can handle
      multiple diverse inputs could strengthen predictive abilities and improve patient
      outcomes. Inpatient length of stay (LOS) is one such outcome that serves as a
      surrogate for patient disease severity and resource utilization. OBJECTIVE: To
      develop a novel method to systematically rank, select, and combine ML algorithms
      to build a model that predicts LOS following craniotomy for brain tumor. METHODS:
      A training dataset of 41 222 patients who underwent craniotomy for brain tumor
      was created from the National Inpatient Sample. Twenty-nine ML algorithms were
      trained on 26 preoperative variables to predict LOS. Trained algorithms were
      ranked by calculating the root mean square logarithmic error (RMSLE) and top
      performing algorithms combined to form an ensemble. The ensemble was externally
      validated using a dataset of 4592 patients from the National Surgical Quality
      Improvement Program. Additional analyses identified variables that most strongly
      influence the ensemble model predictions. RESULTS: The ensemble model predicted
      LOS with RMSLE of .555 (95% confidence interval, .553-.557) on internal
      validation and .631 on external validation. Nonelective surgery, preoperative
      pneumonia, sodium abnormality, or weight loss, and non-White race were the
      strongest predictors of increased LOS. CONCLUSION: An ML ensemble model predicts
      LOS with good performance on internal and external validation, and yields
      clinical insights that may potentially improve patient outcomes. This systematic
      ML method can be applied to a broad range of clinical problems to improve patient
      care.

PMID- 30113666
TI  - Prevalence and control of hypertension by 48-h ambulatory blood pressure
      monitoring in haemodialysis patients: a study by the European Cardiovascular and
      Renal Medicine (EURECA-m) working group of the ERA-EDTA.

PMID- 30113669
TI  - Commentary: Translational Medicine and Neurosurgery: Chance and the Prepared
      Mind.

PMID- 30113668
TI  - The interplay between the Argonaute proteins Piwi and Aub within Drosophila
      germarium is critical for oogenesis, piRNA biogenesis and TE silencing.
AB  - Transposable elements (TEs) have invaded most genomes and constitute up to 50% of
      the human genome. Machinery based on small non-coding piRNAs has evolved to
      inhibit their expression at the transcriptional and post-transcriptional levels.
      Surprisingly, this machinery is weakened during specific windows of time in mice,
      flies or plants, allowing the expression of TEs in germline cells. The function
      of this de-repression remains unknown. In Drosophila, we have previously shown
      that this developmental window is characterized by a reduction of Piwi expression
      in dividing germ cells. Here, we show that the unique knock-down of Aub in these
      cells leads to female sterility. It correlates with defects in piRNA
      amplification, an increased Piwi expression and an increased silencing of
      transcriptionally silenced TEs. These defects are similar to those observed when
      Aub is depleted in the whole germline which underlies the crucial role of this
      developmental window for both oogenesis and TE silencing. We further show that,
      with age, some fertility is recovered which is concomitant to a decrease of Piwi
      and TE silencing. These data pinpoint the Pilp as a tremendously important step
      for female fertility and genome stability. They further show that such a
      restricted developmental niche of germ cells may sense environmental changes,
      such as aging, to protect the germline all along the life.

PMID- 30113671
TI  - A Tribute to Dr Robert J. White.
AB  - Robert J. White is probably best known as the first neurosurgeon to perform
      successful "cephalic exchange" on monkeys in 1971. However, he was also a pioneer
      in the field of neurosurgery and contributed tremendously to the field of
      neuroanesthesia and bioethics. White received medical training at the University
      of Minnesota, Harvard University, Peter Bent Brigham Hospital, and Mayo Clinic
      before becoming the first Chief of Neurosurgery at Metrohealth Hospital in
      Cleveland, Ohio. He made significant strides in the field of spinal cord cooling
      and hypothermia. White and his team was also the first to successfully isolate
      the monkey brain with retention of biological activity. In 2004 and 2006, White
      and colleagues were nominated for the Nobel Prize in Physiology and Medicine,
      with Harvey Cushing and Wilder Penfield being the only other 2 neurosurgeons ever
      to be nominated for the award. Aside from his career as a neurosurgeon, he was
      also an advisor to 2 popes and an advocate for animal research. By the end of his
      career, White performed over 10 000 brain operations and published over 1000
      articles, which has pushed the frontiers of neurosurgical research.

PMID- 30113670
TI  - In vivo cleavage rules and target repertoire of RNase III in Escherichia coli.
AB  - Bacterial RNase III plays important roles in the processing and degradation of
      RNA transcripts. A major goal is to identify the cleavage targets of this
      endoribonuclease at a transcriptome-wide scale and delineate its in vivo cleavage
      rules. Here we applied to Escherichia coli grown to either exponential or
      stationary phase a tailored RNA-seq-based technology, which allows transcriptome
      wide mapping of RNase III cleavage sites at a nucleotide resolution. Our analysis
      of the large-scale in vivo cleavage data substantiated the established cleavage
      pattern of a double cleavage in an intra-molecular stem structure, leaving 2-nt
      long 3' overhangs, and refined the base-pairing preferences in the cleavage site
      vicinity. Intriguingly, we observed that the two stem positions between the
      cleavage sites are highly base-paired, usually involving at least one G-C or C-G
      base pair. We present a clear distinction between intra-molecular stem structures
      that are RNase III substrates and intra-molecular stem structures randomly
      selected across the transcriptome, emphasizing the in vivo specificity of RNase
      III. Our study provides a comprehensive map of the cleavage sites in both intra
      molecular and inter-molecular duplex substrates, providing novel insights into
      the involvement of RNase III in post-transcriptional regulation in the bacterial
      cell.

PMID- 30113667
TI  - The Relation Between Thyroid Function and Anemia: A Pooled Analysis of Individual
      Participant Data.
AB  - Context: Anemia and thyroid dysfunction often co-occur, and both increase with
      age. Human data on relationships between thyroid disease and anemia are scarce.
      Objective: To investigate the cross-sectional and longitudinal associations
      between clinical thyroid status and anemia. Design: Individual participant data
      meta-analysis. Setting: Sixteen cohorts participating in the Thyroid Studies
      Collaboration (n = 42,162). Main Outcome Measures: Primary outcome measure was
      anemia (hemoglobin <130 g/L in men and <120 g/L in women). Results: Cross
      sectionally, participants with abnormal thyroid status had an increased risk of
      having anemia compared with euthyroid participants [overt hypothyroidism, pooled
      OR 1.84 (95% CI 1.35 to 2.50), subclinical hypothyroidism 1.21 (1.02 to 1.43),
      subclinical hyperthyroidism 1.27 (1.03 to 1.57), and overt hyperthyroidism 1.69
      (1.00 to 2.87)]. Hemoglobin levels were lower in all groups compared with
      participants with euthyroidism. In the longitudinal analyses (n = 25,466 from 14
      cohorts), the pooled hazard ratio for the risk of development of anemia was 1.38
      (95% CI 0.86 to 2.20) for overt hypothyroidism, 1.18 (1.00 to 1.38) for
      subclinical hypothyroidism, 1.15 (0.94 to 1.42) for subclinical hyperthyroidism,
      and 1.47 (0.91 to 2.38) for overt hyperthyroidism. Sensitivity analyses excluding
      thyroid medication or high levels of C-reactive protein yielded similar results.
      No differences in mean annual change in hemoglobin levels were observed between
      the thyroid hormone status groups. Conclusion: Higher odds of having anemia were
      observed in participants with both hypothyroid function and hyperthyroid
      function. In addition, reduced thyroid function at baseline showed a trend of
      increased risk of developing anemia during follow-up. It remains to be assessed
      in a randomized controlled trial whether treatment is effective in reducing
      anemia.

PMID- 30113672
TI  - Augmented Zika and dengue neutralizing antibodies are associated with Guillain
      Barre syndrome.
AB  - The role of neutralizing antibodies in Zika-induced Guillain-Barre syndrome (GBS)
      has not yet been investigated. We conducted a case-control study using sera from
      the 2016 Zika epidemic in Colombia to determine the neutralizing antibody
      activity against Zika virus (ZIKV) and dengue virus serotype 2 (DENV2). We
      observed increased neutralizing antibody titers against DENV2 in ZIKV-infected
      individuals compared to uninfected controls and higher titers to both ZIKV and
      DENV2 in ZIKV-infected patients diagnosed with GBS compared to non-GBS ZIKV
      infected controls. These data suggest that high neutralizing antibodies titers to
      DENV and to ZIKV are associated with GBS during ZIKV infection.

PMID- 30113673
TI  - Incubation, not sleep, aids problem-solving.
AB  - Solving a novel problem and finding innovative solutions requires a flexible and
      creative recombination of prior knowledge. It is thought that setting a problem
      aside before giving it another try aids problem-solving. The underlying
      mechanisms of such an incubation period could include unconscious processing that
      fosters spreading activation along associated networks and the restructuring of
      problem representations. Recently, it has been suggested that sleep may also
      support problem-solving by supporting the transformation and restructuring of
      memory elements. Since the effect of sleep on problem-solving has been mainly
      tested using the Remote Associates Test, we chose three different tasks-classical
      riddles, visual change detection, and anagrams-to examine various aspects of
      problem-solving and to pinpoint task-specific prerequisites for effects of sleep
      or incubation to emerge. Sixty-two participants were given two attempts to solve
      the problems. Both attempts either occurred consecutively or were spaced apart by
      a 3-hour incubation interval that was spent awake or asleep. We found that a
      period of incubation positively affected solutions rates in classical riddles,
      but not in visual change detection or anagram solving. Contrary to our
      hypothesis, spending the incubation period asleep, did not yield any additional
      benefit. Our study thus supports the notion that a period of letting a problem
      rest is beneficial for its solution and confines the role of sleep to memory
      transformations that do not directly impact on problem-solving ability.

PMID- 30113676
TI  - Steroid Use Associated With Increased Odds of 30-Day Mortality in Surgical
      Patients With Metastatic Spinal Tumors in the Setting of Disseminated Disease.
AB  - BACKGROUND: Steroid administration is part of a standard treatment regimen in
      metastatic spinal cord compression, though the appropriate dose, duration,
      efficacy, and risks remain controversial. OBJECTIVE: To analyze the risk of
      preoperative steroid use on 30-d mortality in surgical metastatic spinal tumors
      with dissemination disease using a large multicenter national database. METHODS:
      Adult patients who underwent surgical treatment for metastatic spine tumors
      between 2005 and 2014 were identified in the American College of Surgeons
      National Surgical Quality Improvement Program database. Demographic, preoperative
      risk factors, operative information, and postoperative events were extracted.
      Multivariate logistical regression modeling was used to investigate the
      association with preoperative steroid use with the outcome of interest, 30-d
      mortality. Other independent risk factors associated with 30-d mortality were
      also identified. RESULTS: Five hundred fifty-two patients underwent surgical
      treatment of spinal metastases with disseminated cancer present at time of
      surgery. Independent risk factors of 30-d mortality included prolonged steroid
      use (odds ratio [OR] 2.48, 95% confidence interval [CI]: 1.22-5.04, P = .012),
      dependent functional status (OR 2.91, 95% CI: 1.68-5.04, P < .001), history of
      bleeding disorder (OR 2.80, 95% CI: 1.16-6.74, P = .021), history of smoking (OR
      2.26, 95% CI: 1.11-4.61, P = .024), preoperative transfusions (OR 2.91, 95% CI:
      1.02-8.29, P = .049), and preoperative infection/sepsis (OR 2.67, 95% CI: 1.18
      6.08, P = .02). Our model demonstrates very strong predictive capabilities, with
      an area under the receiver operating characteristic curve of 0.7447. CONCLUSION:
      Steroid use is associated with a significant increased risk of 30-d mortality in
      surgical metastatic spine tumor patients with disseminated disease. These
      findings warrant further investigation in controlled experimental environments.

PMID- 30113674
TI  - Impact of Aneurysm Multiplicity on Treatment and Outcome After Aneurysmal
      Subarachnoid Hemorrhage.
AB  - BACKGROUND: One-third of patients with aneurysmal subarachnoid hemorrhage (aSAH)
      have multiple intracranial aneurysms (MIA). OBJECTIVE: To determine the
      predictors of outcome in aSAH patients with MIA compared to aSAH patients with a
      single intracranial aneurysm (SIA). METHODS: The Swiss Study of Subarachnoid
      Hemorrhage dataset 2009-2014 was used to evaluate outcome in aSAH patients with
      MIA compared to patients with SIA with the aid of descriptive and multivariate
      regression analysis. The primary endpoints of this cohort study were presence of
      new stroke on computed tomography (CT) after aneurysm treatment, and presence of
      stroke on CT prior to discharge. The secondary endpoints were the clinical and
      the functional status, and the overall mortality at discharge and at 1 yr.
      RESULTS: Among 1689 consecutive patients, 467 had MIA (prevalence: 26.4%). The
      incidence of stroke was higher in the MIA than in the SIA group, both after
      aneurysm treatment (19.3% vs 15.1%) and at discharge (24% vs 21.4%). However, the
      95% confidence interval (CI) for the corresponding odds ratio (OR) in our
      multivariate model included 1, indicating that the detected trends did not reach
      statistical significance. As for the secondary endpoints, aneurysm multiplicity
      was found to be an independent, statistically significant predictor for
      occurrence of a new focal neurological deficit between admission and discharge
      (OR 1.40, 95% CI 1.08-1.81). Yet, the MIA and SIA groups did not differ in terms
      of either functional outcome or overall survival. CONCLUSION: aSAH patients with
      MIA have a higher short-term morbidity than patients with SIA. This excess
      morbidity does not worsen the functional outcome or lower overall survival.

PMID- 30113675
TI  - Interferon-alpha Triggers Autoimmune Thyroid Diseases via Lysosomal-Dependent
      Degradation of Thyroglobulin.
AB  - Context: Autoimmune thyroid diseases (AITDs) arise from complex interactions
      among genetic, epigenetic, and environmental factors. Thyroglobulin (TG) is a
      major susceptibility gene for both Graves disease and Hashimoto thyroiditis.
      Interferon-alpha (IFNalpha), a cytokine secreted during viral infections, has
      emerged as a key trigger of AITD. We have shown that IFNalpha upregulates TG
      transcription; however, how the upregulation of TG transcription by IFNalpha
      triggers AITD is still unknown. Objective: To evaluate how IFNalpha triggers AITD
      by testing its effects on TG processing. Design: We exposed human thyroid cells
      to IFNalpha and evaluated its effects on TG expression and processing. Results:
      Human thyroid cells exposed to INFalpha had increased levels of TG mRNA but
      reduced TG protein levels, indicating TG protein degradation. IFNalpha induced
      endoplasmic reticulum stress, but surprisingly, neither the use of chemical
      chaperones nor proteasome inhibitor prevented IFNalpha-induced TG degradation.
      IFNalpha also increased LysoTracker staining and autophagy flux measured by net
      light chain 3 (LC3)-II and p62 fluxes. In addition, expression of autophagy
      markers LC3 and autophagy-related gene 5 was higher in thyroid tissues from
      patients with AITD. Finally, blocking lysosomal degradation prevented IFNalpha
      induced degradation of TG. Conclusion: We have shown in this study IFNalpha
      induced lysosomal-dependent degradation of TG in human thyroid cells. Our
      findings suggest that during viral infections, local thyroidal IFNalpha
      production can lead to lysosomal TG degradation, releasing pathogenic TG peptides
      that can trigger AITD.

PMID- 30113677
TI  - Leukopenia and lack of ribavirin predict poor outcomes in patients with
      haematological malignancies and respiratory syncytial virus infection.
AB  - Objectives: Respiratory syncytial virus (RSV) infection causes morbidity and
      mortality in cancer patients. However, studies describing this infection in
      patients with haematological malignancies are scarce. We sought to evaluate the
      clinical impact of RSV infection on this patient population. Methods: We reviewed
      the records of patients with haematological malignancies and RSV infections cared
      for at our institution between January 2000 and March 2013. Results: Of the 181
      patients, 71 (39%) had AML, ALL or myelodysplastic syndrome, 12 (7%) had CML or
      CLL, 4 (2%) had Hodgkin lymphoma, 35 (19%) had non-Hodgkin lymphoma and 59 (33%)
      had multiple myeloma. Most patients [117 (65%)] presented with an upper
      respiratory tract infection (URTI) and 15 (13%) had a subsequent lower
      respiratory tract infection (LRTI). The overall LRTI rate was 44% and the 90 day
      mortality rate was 15%. Multivariable regression analysis showed that having both
      neutropenia and lymphocytopenia (adjusted OR = 7.17, 95% CI = 1.94-26.53, P <
      0.01) and not receiving ribavirin-based therapy during RSV URTI (adjusted OR =
      0.03; 95% CI = 0.01-0.11, P < 0.001) were independent risk factors for LRTI.
      Having both neutropenia and lymphocytopenia at RSV diagnosis was also a risk
      factor for death at 90 days after RSV diagnosis (adjusted OR = 4.32, 95% CI =
      1.24-15.0, P = 0.021). Conclusions: Patients with haematological malignancies and
      RSV infections, especially those with immunodeficiency, may be at risk of LRTI
      and death; treatment with ribavirin during RSV URTI may prevent these outcomes.

PMID- 30113678
TI  - Lack of dermal penetration of topically applied gentamicin as pharmacokinetic
      evidence indicating insufficient efficacy.
AB  - Background: Treatment of skin and superficial soft tissue infections with
      topically applied antibiotics is a controversial topic, because only few clinical
      studies exist and target site concentrations after topical treatment are widely
      unknown. Objectives: This study aimed to investigate the target site
      concentration of topically applied gentamicin as a potential cause of therapeutic
      failure and to explore if microporation by laser might be used to improve
      penetration of gentamicin through the skin barrier. Methods: Six healthy
      volunteers were included in this cross-over Phase 1 study. On two study days,
      separated by a washout period, microdialysate and plasma sampling was performed
      for 6 h after administration of 500 mg of gentamicin cream on a predefined area.
      On one of the study days the skin was microporated before drug application using
      the P.L.E.A.S.E. Professional laser system. Results: In intact skin, Cmax and AUC
      values were 3.3 +/- 5.64 ng/mL and 5.4 +/- 10.4 ng.h/mL, respectively; thereby
      far under the threshold needed to treat common pathogens. With a Cmax of 474.2 +/
      555.3 ng/mL laser application showed a significant increase in tissue
      penetration and decrease in pharmacokinetic variability; however, even after
      microporation no therapeutically active concentrations were achieved as indicated
      by Cmax/epidemiological cut-off ratios of 0.237 and 0.059 for Staphylococcus
      aureus and Pseudomonas aeruginosa, respectively. Solely after administration on
      microporated skin, plasma concentrations of gentamicin were quantifiable (lower
      limit of quantification 10 pg/mL). Conclusions: This study confirmed that after
      topical administration gentamicin penetration through the dermal barrier is
      insufficient, providing pharmacokinetic evidence that topical gentamicin in its
      current form might be inappropriate to treat skin infections.

PMID- 30113679
TI  - A novel IncA plasmid carrying blaVIM-1 in a Kluyvera cryocrescens strain.

PMID- 30113680
TI  - Aortic valve construction using pericardial tissue: short-term single-centre
      outcomes.
AB  - OBJECTIVES: Aortic valve construction using pericardial tissue has been known
      since the late 1960s. The procedure was re-introduced by Ozaki in 2010 and is
      currently used to treat specific aortic valve diseases. The exact sizing of the
      neo-cusps and the insertion of the commissures remain the keys to success when
      performing this procedure. We evaluated our experience using modified custom-made
      templates. METHODS: In this prospective single-centre study, we evaluated 52
      consecutive patients who underwent aortic valve construction between September
      2015 and March 2017 using either autologous (16 patients, 30.8%) or tissue
      engineered pericardium (36 patients, 69.2%). Most patients (34, 65.4%) presented
      with aortic stenosis or endocarditis (5, 9.6%). Twenty patients had bicuspid and
      5 had unicuspid valves. A modified sizing technique with specially designed
      templates was used. The primary end point was early death; the secondary end
      points were major adverse cardiac and cerebrovascular events, freedom from
      reoperation and overall mortality rate. Echocardiographic follow-up was performed
      intraoperatively and at 12-month intervals. RESULTS: The mean age was 60 +/- 14
      years; 63.5% were men; and 34 (65.4%) patients had combined procedures. The mean
      cross-clamp time was 99 +/- 17 min. Early outcomes included 1 stroke, 2 patients
      needing short-term dialysis and 1 death. During follow-up (mean 11.2 +/- 4.8
      months), trace aortic regurgitation was observed in 4 patients; the mean pressure
      gradient was 6.8 +/- 2.9 mmHg. Three patients died later (of non-cardiac
      reasons), and 5 patients needed reoperation due to endocarditis. CONCLUSIONS:
      Aortic valve construction using pericardial tissue could be an alternative in
      middle-age patients presenting with aortic valve disease in whom valve repair was
      not possible. The newly designed templates allow exact sizing of the neo-cusps
      and optimal commissure implantation; however, long-term follow-up in a larger
      cohort is warranted to assess the durability of the neo-valves.

PMID- 30113681
TI  - Development of an algorithm to link electronic health record prescriptions with
      pharmacy dispense claims.
AB  - Objective: Medication adherence is an important aspect of chronic disease
      management. Electronic health record (EHR) data are often not linked to
      dispensing data, limiting clinicians' understanding of which of their patients
      fill their medications, and how to tailor care appropriately. We aimed to develop
      an algorithm to link EHR prescribing to claims-based dispensing data and use the
      results to quantify how often patients with diabetes filled prescribed chronic
      disease medications. Materials and Methods: We developed an algorithm linking EHR
      prescribing data (RxNorm terminology) to claims-based dispensing data (NDC
      terminology), within sample of adult (19-64) community health center (CHC)
      patients with diabetes from a network of CHCs across 12 states. We demonstrate an
      application of the method by calculating dispense rates for a set of commonly
      prescribed diabetes and cardio-protective medications. To further inform clinical
      care, we computed adjusted odds ratios of dispense by patient-, encounter-, and
      clinic-level characteristics. Results: Seventy-six percent of cardio-protective
      medication prescriptions and 74% of diabetes medications were linked to a
      dispensing record. Age, income, ethnicity, insurance, assigned primary care
      provider, comorbidity, time on EHR, and clinic size were significantly associated
      with odds of dispensing. Discussion: EHR prescriptions and pharmacy dispense data
      can be linked at the record level across different terminologies. Dispensing
      rates in this low-income population with diabetes were similar to other
      populations. Conclusion: Record linkage resulted in the finding that CHC patients
      with diabetes largely had their chronic disease medications dispensed.
      Understanding factors associated with dispensing rates highlight barriers and
      opportunities for optimal disease management.

PMID- 30113682
TI  - Emergence of a vancomycin-variable Enterococcus faecium ST1421 strain containing
      a deletion in vanX.
AB  - Background: Primary screening for VRE with PCR directed against vanA allowed
      identification of vanA+ samples from which VRE could not be isolated when
      selective culture methods were used. From such a sample a vancomycin-susceptible,
      vanA+ Enterococcus faecium, Efm-V1511, was isolated, when vancomycin selection
      was not used during culture. Similar isolates with variable susceptibility to
      vancomycin were obtained in the following months. Objectives: To characterize Efm
      V1511 and investigate the causes of variable susceptibility to vancomycin.
      Methods: All strains were sequenced using Illumina technology. Plasmids
      containing vanA were reconstructed by scaffolding to known plasmids or plasmids
      were sequenced using Oxford Nanopore MinION. Derived structures were verified by
      PCR and sequencing. Furthermore, selected vanA+ vancomycin-susceptible isolates
      were passaged in the presence of vancomycin and vancomycin-resistant variants
      obtained were sequenced. Results: Efm-V1511 belonged to ST1421 and contained a 49
      696 bp plasmid pHVH-V1511 carrying a Tn1546-derived genetic element. Within this
      element vanX was truncated by a 252 bp 3' deletion explaining the susceptibility
      of Efm-V1511. Between March 2016 and April 2017, 48 isolates containing pHVH
      V1511 were identified. All were ST1421. In isolates resistant to vancomycin,
      resistance could be attributed to changes in ddl disrupting gene function
      sometimes accompanied by changes in vanS, increased pHVH-V1511 copy number or the
      existence of an additional vanA-containing plasmid encoding a functional vanX.
      Conclusions: E. faecium carrying pHVH-V1511 is capable of nosocomial transmission
      and may develop clinical resistance to vancomycin. Strains may not be detected
      using standard culture methods for VRE.

PMID- 30113683
TI  - Cortisol Excess in Patients With Primary Aldosteronism Impacts Left Ventricular
      Hypertrophy.
AB  - Context: Primary aldosteronism (PA) represents the most frequent form of
      endocrine hypertension. Hyperaldosteronism and hypercortisolism both induce
      excessive left ventricular hypertrophy (LVH) compared with matched essential
      hypertensives. In recent studies frequent cosecretion of cortisol and aldosterone
      has been reported in patients with PA. Objective: Our aim was to investigate the
      impact of cortisol cosecretion on LVH in patients with PA. We determined 24-hour
      excretion of mineralocorticoids and glucocorticoids by gas chromatography-mass
      spectrometry and assessed cardiac remodeling using echocardiography initially and
      1 year after initiation of treatment of PA. Patients: We included 73 patients
      from the Munich center of the German Conn's registry: 45 with unilateral
      aldosterone-producing adenoma and 28 with bilateral adrenal hyperplasia. Results:
      At the time of diagnosis, 85% of patients with PA showed LVH according to left
      ventricular mass index [(LVMI); median 62.4 g/m2.7]. LVMI correlated positively
      with total glucocorticoid excretion (r2 = 0.076, P = 0.018) as well as with
      tetrahydroaldosterone excretion (r2 = 0.070, P = 0.024). Adrenalectomy led to
      significantly reduced LVMI in aldosterone-producing adenoma (P < 0.001) whereas
      mineralocorticoid receptor antagonist therapy in bilateral adrenal patients with
      hyperplasia reduced LVMI to a lesser degree (P = 0.024). In multivariate
      analysis, the decrease in LVMI was positively correlated with total
      glucocorticoid excretion and systolic 24-hour blood pressure, but not with
      tetrahydroaldosterone excretion. Conclusion: Cortisol excess appears to have an
      additional impact on cardiac remodeling in patients with PA. Treatment of PA by
      either adrenalectomy or mineralocorticoid receptor antagonist improves LVMI. This
      effect was most pronounced in patients with high total glucocorticoid excretion.

PMID- 30113684
TI  - Loss of BCAT1 Expression is a Sensitive Marker for IDH-Mutant Diffuse Glioma.
AB  - BACKGROUND: IDH mutation is an important prognostic factor of diffuse
      astrocytomas. Although the majority of IDH mutations could be identified by
      immunohistochemical (IHC) stain for R132H-mutant IDH1, DNA sequencing would be
      required for IHC negative cases to determine their IDH mutation status. This
      approach is not cost-effective for tumors with low IDH mutation rates. OBJECTIVE:
      To investigate whether BCAT1 could be used as a surrogate marker for IDH
      mutations, because BCAT1 is an enzyme related to IDH genes. METHODS: A group of
      120 anaplastic astrocytomas were immunostained for BCAT1, ATRX, and R132H-mutant
      IDH1. Staining results correlated with the results of DNA sequencing of
      IDH1/IDH2. RESULTS: DNA sequencing showed IDH1/2 mutations in 50.8% of cases of
      which 73.8% had IDH1 R132H mutation. Several IDH1 noncodon 132 mutations, ie,
      G97D, S122N, G123E, I130K, and G131S, which had uncertain prognostic
      significance, were identified. IHC stain for R132H-mutant IDH1 identified 93.3%
      of IDH1 R132H mutations and 70.5% of all IDH mutations. BCAT1 loss was seen in
      65.8% of cases, its sensitivity to identify IDH mutations was 96.7%. The
      sensitivity reached 100% for IDH1 codon 132 and IDH2 codon 172 mutations.
      CONCLUSION: Positive BCAT1 stain could be used to exclude diffuse gliomas with
      IDH1 codon 132 and IDH2 codon 172 mutations. Selecting cases with negative BCAT1
      and R132H-mutant IDH1 staining for DNA sequencing of IDH1/2 genes could improve
      the cost-effectiveness of detecting IDH mutations particularly in tumors with low
      IDH mutation rates, and confine the need of 1p/19q assay in IDH-mutant tumors.

PMID- 30113685
TI  - Improved Quality of Recovery from Ambulatory Shoulder Surgery After
      Implementation of a Multimodal Perioperative Pain Management Protocol.
AB  - Objectives: Pain control after shoulder arthroscopy can be challenging, often
      relying on opioids. The study aims to measure the quality of recovery (QoR)
      before and after implementation of a "Multimodal Perioperative Pain Protocol"
      (MP3) in patients undergoing ambulatory shoulder arthroscopy. Design: Prospective
      cohort study. Setting: Free-standing ambulatory surgery facility of a tertiary
      care academic center. Subjects: Patients undergoing ambulatory shoulder
      arthroscopy. Methods: The primary end point of the study was the QoR-9 score at
      24 hours, 48 hours, and one week after surgery. Secondary end points included 1)
      measuring the quality of pain management using the Revised American Pain Society
      Patient Oriented Questionnaire (APS-POQ-R) and 2) postoperative opioid
      requirements. Results: Data from132 patients in the control group (pre
      intervention) and 120 patients in the MP3 group were analyzed. The QoR-9 scores
      were significantly higher for the MP3 group at all time points, but only met the
      minimal clinical important difference threshold at 24 hours (13.4 vs 14.9, P <
      0.05) and 48 hours (14.0 vs 15.0, P < 0.05) postoperatively. Patients reported
      better quality of pain management after implementation of the MP3 in the domains
      of pain intensity, pain interference with activity, and sleep, and they reported
      the presence of negative emotions up to two days after ambulatory shoulder
      surgery. In addition, this protocol significantly reduced opioid consumption up
      to three days after surgery. Conclusions: Implementation of the MP3 improved the
      overall QoR and many aspects of postoperative pain relief while reducing total
      opioid consumption in patients undergoing ambulatory shoulder surgery.

PMID- 30113686
TI  - Risk Factors Associated With 90-Day Readmissions After Degenerative Lumbar
      Fusion: An Examination of the Michigan Spine Surgery Improvement Collaborative
      (MSSIC) Registry.
AB  - BACKGROUND: Most studies have evaluated 30-d readmissions after lumbar fusion
      surgery. Evaluation of the 90-d period, however, allows a more comprehensive
      assessment of factors associated with readmission. OBJECTIVE: To assess the
      reasons and risk factors for 90-d readmissions after lumbar fusion surgery.
      METHODS: The Michigan Spine Surgery Improvement Collaborative (MSSIC) registry is
      a prospective, multicenter, and spine-specific database of patients surgically
      treated for degenerative disease. MSSIC data were retrospectively analyzed for
      causes of readmission, and independent risk factors impacting readmission were
      found by multivariate logistic regression. RESULTS: Of 10 204 patients who
      underwent lumbar fusion, 915 (9.0%) were readmitted within 90 d, most commonly
      for pain (17%), surgical site infection (16%), and radicular symptoms (10%). Risk
      factors associated with increased likelihood of readmission were other race (odds
      ratio [OR] 1.81, confidence interval [CI] 1.22-2.69), coronary artery disease (OR
      1.57, CI 1.25-1.96), >=4 fused levels (OR 1.41, CI 1.06-1.88), diabetes (OR 1.34,
      CI 1.10-1.63), and surgery length (OR 1.09, CI 1.03-1.16). Factors associated
      with decreased risk were discharge to home (OR 0.63, CI 0.51-0.78), private
      insurance (OR 0.79, CI 0.65-0.97), ambulation same day of surgery (OR 0.81, CI
      0.67-0.97), and spondylolisthesis diagnosis (OR 0.82, CI 0.68-0.97). Of those
      readmitted, 385 (42.1%) patients underwent another surgery. CONCLUSION: Ninety
      day readmission occurred in 9.0% of patients, mainly for pain, wound infection,
      and radicular symptoms. Increased focus on postoperative pain may decrease
      readmissions. Among factors impacting the likelihood of 90-d readmission, early
      postoperative ambulation may be most easily modifiable. Optimization of
      preexisting medical conditions could also potentially decrease readmission risk.

PMID- 30113687
TI  - Folate Receptor Overexpression in Human and Canine Meningiomas
      Immunohistochemistry and Case Report of Intraoperative Molecular Imaging.
AB  - BACKGROUND: Meningiomas are well-encapsulated benign brain tumors and surgical
      resection is often curative. Nevertheless, this is not always possible due to the
      difficulty of identifying residual disease intraoperatively. We hypothesized that
      meningiomas overexpress folate receptor alpha (FRalpha), allowing intraoperative
      molecular imaging by targeting FRalpha with a near-infrared (NIR) dye. OBJECTIVE:
      To determine FRalpha expression in both human and canine meningioma cohorts to
      prepare for future clinical studies. Present a case study of a meningioma
      resection with intraoperative NIR fluorescence imaging. METHODS: Tissue samples
      of 27 human meningioma specimens and 7 canine meningioma specimens were
      immunohistochemically stained for FRalpha along with normal dura, skeletal
      muscle, and kidney tissue. We then enrolled a patient with a pituitary adenoma
      and tuberculum sella meningioma in a clinical trial in which the patient received
      an infusion of folate-linked, NIR fluorescent dye prior to surgery. RESULTS: In
      the cohort of human meningiomas, 9 WHO grade I, 12 grade II, and 6 grade III
      tumors were identified. Eighty-nine percent of WHO grade I, 67% of grade II, and
      50% of grade III tumors overexpressed FRalpha. In the 7 canine meningioma
      samples, 100% stained positively for FRalpha. Both human and canine normal dura
      from autopsy samples demonstrated no evidence of FRalpha overexpression. In the
      case study, the meningioma demonstrated a high NIR signal-to-background-ratio of
      4.0 and demonstrated strong FRalpha immunohistochemistry staining. CONCLUSION:
      This study directly demonstrates FRalpha overexpression in both human and canine
      meningiomas. We also demonstrate superb intraoperative imaging of a meningioma
      using a FRalpha-targeting dye.

PMID- 30113688
TI  - Natural variation of DNA methylation and gene expression may determine local
      adaptations of Scots pine populations.
AB  - Long-lived conifers are vulnerable to climate change because classical
      evolutionary processes are slow in developing adaptive responses. Therefore, the
      capacity of a genotype to adopt different phenotypes is important. Gene
      expression is the primary mechanism that converts genome-encoded information into
      phenotypes, and DNA methylation is employed in the epigenetic regulation of gene
      expression. We investigated variations in global DNA methylation and gene
      expression between three Scots pine (Pinus sylvestris L.) populations located in
      northern and southern Finland using mature seeds. Gene expression levels were
      studied in six DNA methyltransferase (DNMT) genes, which were characterized in
      this study, and in 19 circadian clock genes regulating adaptive traits. In
      embryos, expression diversity was found for three DNMT genes, which maintain DNA
      methylation. The expression of two DNMT genes was strongly correlated with
      climate variables, which suggests a role for DNA methylation in local adaptation.
      For adaptation-related genes, expression levels showed between-population
      variation in 11 genes in megagametophytes and in eight genes in embryos, and many
      of these genes were linked to climate factors. Altogether, our results suggest
      that differential DNA methylation and gene expression contribute to local
      adaptation in Scots pine populations and may enhance the fitness of trees under
      rapidly changing climatic conditions.

PMID- 30113691
TI  - Update From the Advisory Committee on Immunization Practices.
AB  - The Advisory Committee on Immunization Practices (ACIP), a group of medical and
      public health experts, meets 3 times per year to develop recommendations for
      vaccine use in the United States. The group has 15 voting members, and each
      member's term is 4 years. ACIP members and Centers for Disease Control and
      Prevention staff discuss the epidemiology of vaccine-preventable diseases and
      vaccine research, effectiveness, safety data, and clinical trial results.
      Representatives from the American Academy of Pediatrics (J. D. C. and D. W. K.)
      and the Pediatric Infectious Diseases Society (S. T. O.) are present as liaisons
      to the ACIP. The ACIP met on June 20 and 21, 2018, to discuss influenza vaccine
      effectiveness and safety, anthrax vaccination in the setting of a mass exposure,
      human papillomavirus vaccine, mumps vaccine, Japanese encephalitis vaccine, and
      pneumococcal vaccination among adults.

PMID- 30113689
TI  - Dengue infection in international travellers visiting Bali, Indonesia.
AB  - Background: Dengue, an acute febrile illness caused by infection with dengue
      virus (DENV), is endemic in Bali, Indonesia. As one of the world's most popular
      tourist destinations, Bali is regularly visited by domestic and international
      travellers, who are prone to infection by endemic pathogens, including DENV.
      Currently, limited data are available on the characteristics of dengue in
      travellers visiting Bali. Information on the epidemiology and virological aspects
      of dengue in these tourists is important to gain a better understanding of the
      dengue disease in international travellers. Methods: We performed a prospective
      cross-sectional dengue study involving foreign travellers visiting Bali,
      Indonesia in the period of 2015-17. Patients presenting at Kasih Ibu Hospital
      with fever and clinical symptoms of dengue were asked to participate in the
      study. Clinical and laboratory assessments were performed and sera were collected
      for molecular analysis, which included DENV serotyping, genome sequencing and
      phylogenetic analysis. Results: Among the 201 patients recruited, dengue was
      confirmed in 133 (66.2%) of them, based on detection of NS1 antigen and/or viral
      RNA. Of these, 115 (86.5%) manifested dengue fever (DF) and 18 (13.5%) dengue
      haemorrhagic fever (DHF). The temporal predominance of infecting DENV serotype
      was DENV-2 (48.7%), followed by DENV-3 (36.1%), DENV-1 (9.2%) and DENV-4 (3.4%).
      Phylogenetic analysis of DENV based on envelope gene sequences revealed that the
      source of DENVs was local endemic viruses. Conclusion: Our study confirms that
      dengue is one of the causes of fever in travellers visiting Bali. Although it is
      a cause of significant morbidity, the majority of patients only experienced mild
      DF, with only a small proportion developing DHF. We revealed that DENVs isolated
      were autochthonous. Accurate diagnosis, preventive measures and continuous
      disease surveillance will be useful for better management of dengue infection in
      travellers.

PMID- 30113690
TI  - Function of pea amino acid permease AAP6 in nodule nitrogen metabolism and
      export, and plant nutrition.
AB  - Legumes fix atmospheric nitrogen through a symbiotic relationship with bacteroids
      in root nodules. Following fixation in pea (Pisum sativum L.) nodules, nitrogen
      is reduced to amino acids that are exported via the nodule xylem to the shoot,
      and in the phloem to roots in support of growth. However, the mechanisms involved
      in amino acid movement towards the nodule vasculature, and their importance for
      nodule function and plant nutrition, were unknown. We found that in pea nodules
      the apoplasmic pathway is an essential route for amino acid partitioning from
      infected cells to the vascular bundles, and that amino acid permease PsAAP6 is a
      key player in nitrogen retrieval from the apoplasm into inner cortex cells for
      nodule export. Using an miRNA interference (miR) approach, it was demonstrated
      that PsAAP6 function in nodules, and probably in roots, and affects both shoot
      and root nitrogen supply, which were strongly decreased in PsAAP6-miR plants.
      Further, reduced transporter function resulted in increased nodule levels of
      ammonium, asparagine, and other amino acids. Surprisingly, nitrogen fixation and
      nodule metabolism were up-regulated in PsAAP6-miR plants, indicating that under
      shoot nitrogen deficiency, or when plant nitrogen demand is high, systemic
      signaling leads to an increase in nodule activity, independent of the nodule
      nitrogen status.

PMID- 30113692
TI  - Medication-related quality of care in residential aged care: an Australian
      experience.
AB  - Objective: To describe medication-related quality of care (MRQOC) for Australian
      aged care residents. Design: Retrospective cohort using an administrative
      healthcare claims database. Setting: Australian residential aged care.
      Participants: A total of 17 672 aged care residents who were alive at 1 January
      2013 and had been a permanent resident for at least 3 months. Main outcome
      measures: Overall, 23 evidence-based MRQOC indicators which assessed the use of
      appropriate medications in chronic disease, exposure to high-risk medications and
      access to collaborative health services. Results: Key findings included underuse
      of recommended cardiovascular medications, such as the use of statins in
      cardiovascular disease (56.1%). Overuse of high-risk medications was detected for
      medications associated with falls (73.5%), medications with moderate to strong
      anticholinergic properties (46.1%), benzodiazepines (41.4%) and antipsychotics
      (33.2%). Collaborative health services such as medication reviews were
      underutilised (42.6%). Conclusion: MRQOC activities in this population should be
      targeted at monitoring and reducing exposure to antipsychotics and
      benzodiazepines, improving the use of preventative medications for cardiovascular
      disease and improving access to collaborative health services. Similarity of
      suboptimal MRQOC between Australia and other countries (UK, USA, Canada and
      Belgium) presents an opportunity for an internationally collaborative approach to
      improving care for aged care residents.

PMID- 30113693
TI  - Transcriptomic comparison reveals genetic variation potentially underlying seed
      developmental evolution of soybeans.
AB  - Soybean (Glycine max) was domesticated from its wild relative Glycine soja.
      However, the genetic variations underlying soybean domestication are not well
      known. Comparative transcriptomics revealed that a small portion of the
      orthologous genes might have been fast evolving. In contrast, three gene
      expression clusters were identified as divergent by their expression patterns,
      which occupied 37.44% of the total genes, hinting at an essential role for gene
      expression alteration in soybean domestication. Moreover, the most divergent
      stage in gene expression between wild and cultivated soybeans occurred during
      seed development around the cotyledon stage (15 d after fertilization, G15). A
      module in which the co-expressed genes were significantly down-regulated at G15
      of wild soybeans was identified. The divergent clusters and modules included
      substantial differentially expressed genes (DEGs) between wild and cultivated
      soybeans related to cell division, storage compound accumulation, hormone
      response, and seed maturation processes. Chromosomal-linked DEGs, quantitative
      trait loci controlling seed weight and oil content, and selection sweeps revealed
      candidate DEGs at G15 in the fruit-related divergence of G. max and G. soja. Our
      work establishes a transcriptomic selection mechanism for altering gene
      expression during soybean domestication, thus shedding light on the molecular
      networks underlying soybean seed development and breeding strategy.

PMID- 30113696
TI  - NICE public health guidance update.
AB  - This article covers recent National Institute for Health and Care Excellence
      guidance and standards relevant to public health. The article also includes an
      overview of key public health aspects of the updated 'stop smoking interventions
      and service guideline', summarizing recommendations for commissioners and
      managers as well as individuals in contact with people who smoke.

PMID- 30113695
TI  - The role of phylogenetically conserved elements in shaping patterns of human
      genomic diversity.
AB  - Evolutionary genetic studies have shown a positive correlation between levels of
      nucleotide diversity and either rates of recombination or genetic distance to
      genes. Both positive-directional and purifying selection have been offered as the
      source of these correlations via genetic hitchhiking and background selection,
      respectively. Phylogenetically conserved elements (CEs) are short (~100bp),
      widely distributed (comprising ~5% of genome), sequences that are often found far
      from genes. While the function of many CEs is unknown, CEs also are associated
      with reduced diversity at linked sites. Using high coverage (>80x) whole genome
      data from two human populations, the Yoruba and the CEU, we perform fine scale
      evaluations of diversity, rates of recombination, and linkage to genes. We find
      that the local rate of recombination has a stronger effect on levels of diversity
      than linkage to genes, and that these effects of recombination persist even in
      regions far from genes. Our whole genome modeling demonstrates that, rather than
      recombination or GC-biased gene conversion, selection on sites within or linked
      to CEs better explains the observed genomic diversity patterns. A major
      implication is that very few sites in the human genome are predicted to be free
      of the effects of selection. These sites, which we refer to as the human
      "neutralome", comprise only 1.2% of the autosomes and 5.1% of the X chromosome.
      Demographic analysis of the neutralome reveals larger population sizes and lower
      rates of growth for ancestral human populations than inferred by previous
      analyses.

PMID- 30113694
TI  - Aminoglycoside ribosome interactions reveal novel conformational states at
      ambient temperature.
AB  - The bacterial 30S ribosomal subunit is a primary antibiotic target. Despite
      decades of discovery, the mechanisms by which antibiotic binding induces
      ribosomal dysfunction are not fully understood. Ambient temperature
      crystallographic techniques allow more biologically relevant investigation of how
      local antibiotic binding site interactions trigger global subunit rearrangements
      that perturb protein synthesis. Here, the structural effects of 2
      deoxystreptamine (paromomycin and sisomicin), a novel sisomicin derivative, N1
      methyl sulfonyl sisomicin (N1MS) and the non-deoxystreptamine (streptomycin)
      aminoglycosides on the ribosome at ambient and cryogenic temperatures were
      examined. Comparative studies led to three main observations. First, individual
      aminoglycoside-ribosome interactions in the decoding center were similar for
      cryogenic versus ambient temperature structures. Second, analysis of a highly
      conserved GGAA tetraloop of h45 revealed aminoglycoside-specific conformational
      changes, which are affected by temperature only for N1MS. We report the h44-h45
      interface in varying states, i.e. engaged, disengaged and in equilibrium. Third,
      we observe aminoglycoside-induced effects on 30S domain closure, including a
      novel intermediary closure state, which is also sensitive to temperature.
      Analysis of three ambient and five cryogenic crystallography datasets reveal a
      correlation between h44-h45 engagement and domain closure. These observations
      illustrate the role of ambient temperature crystallography in identifying dynamic
      mechanisms of ribosomal dysfunction induced by local drug-binding site
      interactions. Together, these data identify tertiary ribosomal structural changes
      induced by aminoglycoside binding that provides functional insight and targets
      for drug design.

PMID- 30113697
TI  - Cardiovascular Benefits of Acarbose vs Sulfonylureas in Patients With Type 2
      Diabetes Treated With Metformin.
AB  - Context: Although alpha-glucosidase inhibitors (AGIs) have been shown to reduce
      the risk of myocardial infarction in patients with impaired glucose tolerance,
      the cardiovascular benefits of AGIs in those with type 2 diabetes (T2D) remains
      unclear. Objective: We compared the clinical outcomes of adding acarbose vs
      sulfonylureas to metformin therapy in patients with T2D. Design, Setting, and
      Participants: The study population was drawn from the database of the Diabetes
      Pay-for-Performance program in Taiwan. Sulfonylureas and acarbose were prescribed
      to 196,143 and 14,306 patients with T2D, respectively, from 2004 to 2015, who had
      been treated with metformin. A propensity score-matched cohort study was
      conducted. The patients were followed up for clinical adverse events of all-cause
      mortality and hospitalizations of major atherosclerotic events (i.e., myocardial
      infarction and ischemic stroke), heart failure, or hypoglycemia. Results: A total
      of 14,306 propensity score-matched pairs (age, 55.8 +/- 13.1 years; 47.8% men)
      were enrolled in the present analysis. Compared with sulfonylureas as the add-on
      therapy to metformin, the use of acarbose was associated with significantly lower
      risks of hospitalizations for major atherosclerotic events [hazard ratio (HR),
      0.69; 95% CI, 0.52 to 0.91], ischemic stroke (HR, 0.68; 95% CI, 0.49 to 0.94),
      and hypoglycemia (HR, 0.23; 95% CI, 0.08 to 0.71), after accounting for major
      confounding factors. Conclusions: In T2D treatment, the use of acarbose as an add
      on remedy to metformin was associated with lower risks of major atherosclerotic
      events, ischemic stroke, and hypoglycemia compared with the use of sulfonylurea
      as an add-on remedy.

PMID- 30113699
TI  - Comparison of injectate spread and nerve involvement between retrolaminar and
      erector spinae plane blocks in the thoracic region: a cadaveric study.
AB  - Although different injection locations for retrolaminar and erector spinae plane
      blocks have been described, the two procedures have a similar anatomical basis.
      In this cadaveric study we compared anatomical spread of dye in the thoracic
      region following these two procedures. Following randomisation, 10 retrolaminar
      blocks and 10 erector spinae plane blocks were performed on the left or right
      sides of 10 unembalmed cadavers. For each block, 20 ml of dye solution was
      injected at the T5 level. The back regions were dissected and the involvement of
      the thoracic spinal nerve was also investigated. Twenty blocks were successfully
      completed. A consistent vertical spread, with deep staining between the posterior
      surface of the vertebral laminae and the overlaying transversospinalis muscle was
      observed in all retrolaminar blocks. Moreover, most retrolaminar blocks were
      predominantly associated with fascial spreading in the intrinsic back muscles.
      With an erector spinae plane block, dye spread in a more lateral pattern than
      with retrolaminar block, and fascial spreading in the back muscles was also
      observed. The number of stained thoracic spinal nerves was greater with erector
      spinae plane blocks than with retrolaminar blocks; median 2.0 and 3.5,
      respectively. Regardless of technique, the main route of dye spread was through
      the superior costotransverse ligament to the ipsilateral paravertebral space.
      Although erector spinae plane blocks were associated with a slightly larger
      number of stained thoracic spinal nerves than retrolaminar blocks, both
      techniques were consistently associated with posterior spread of dye and with
      limited spread to the paravertebral space.

PMID- 30113698
TI  - TDP1 suppresses mis-joining of radiomimetic DNA double-strand breaks and
      cooperates with Artemis to promote optimal nonhomologous end joining.
AB  - The Artemis nuclease and tyrosyl-DNA phosphodiesterase (TDP1) are each capable of
      resolving protruding 3'-phosphoglycolate (PG) termini of DNA double-strand breaks
      (DSBs). Consequently, both a knockout of Artemis and a knockout/knockdown of TDP1
      rendered cells sensitive to the radiomimetic agent neocarzinostatin (NCS), which
      induces 3'-PG-terminated DSBs. Unexpectedly, however, a knockdown or knockout of
      TDP1 in Artemis-null cells did not confer any greater sensitivity than either
      deficiency alone, indicating a strict epistasis between TDP1 and Artemis.
      Moreover, a deficiency in Artemis, but not TDP1, resulted in a fraction of
      unrepaired DSBs, which were assessed as 53BP1 foci. Conversely, a deficiency in
      TDP1, but not Artemis, resulted in a dramatic increase in dicentric chromosomes
      following NCS treatment. An inhibitor of DNA-dependent protein kinase, a key
      regulator of the classical nonhomologous end joining (C-NHEJ) pathway sensitized
      cells to NCS, but eliminated the sensitizing effects of both TDP1 and Artemis
      deficiencies. These results suggest that TDP1 and Artemis perform different
      functions in the repair of terminally blocked DSBs by the C-NHEJ pathway, and
      that whereas an Artemis deficiency prevents end joining of some DSBs, a TDP1
      deficiency tends to promote DSB mis-joining.

PMID- 30113700
TI  - Disparities in hepatocellular carcinoma incidence by race/ethnicity and
      geographic area in California: Implications for prevention.
AB  - BACKGROUND: The incidence of hepatocellular carcinoma (HCC) has been rising
      rapidly in the United States. California is an ethnically diverse state with the
      largest number of incident HCC cases in the country. Characterizing HCC
      disparities in California may inform priorities for HCC prevention. METHODS: By
      using data from the Surveillance, Epidemiology, and End Results 18-Registry
      Database and the California Cancer Registry, age-adjusted HCC incidence in
      California from 2009 through 2013 was calculated by race/ethnicity and
      neighborhood ethnic enclave status. A geographic analysis was conducted using
      Medical Service Study Areas (MSSAs) as the geographic unit, and race/ethnicity
      specific standardized incidence ratios (SIRs) were calculated to identify MSSAs
      with higher-than-expected HCC incidence compared with the statewide average.
      RESULTS: During 2009 through 2013, the age-adjusted incidence of HCC in
      California was the highest in Asians/Pacific Islanders (APIs) and Hispanics
      (>100% higher than whites), especially those living in more ethnic neighborhoods
      (20%-30% higher than less ethnic neighborhoods). Of the 542 MSSAs statewide, 42
      had elevated HCC incidence (SIR >= 1.5; lower bound of 95% confidence interval >
      1) for whites, 14 for blacks, 24 for APIs, and 36 for Hispanics. These MSSAs have
      24% to 52% higher proportions of individuals below the 100% federal poverty line
      than other MSSAs. CONCLUSIONS: APIs and Hispanics residing in more ethnic
      neighborhoods and individuals residing in lower income neighborhoods require more
      extensive preventive efforts tailored toward their unique risk factor profiles.
      The current race/ethnicity-specific geographic analysis can be extended to other
      states to inform priorities for HCC targeted prevention at the subcounty level,
      eventually reducing HCC burden in the country.

PMID- 30113701
TI  - Sensitive skin can be small fibre neuropathy: results from a case-control
      quantitative sensory testing study.
AB  - BACKGROUND: Sensitive skin syndrome (SSS) is defined as the occurrence of
      unpleasant sensations (itch, pain, burning, prickling) in response to stimuli
      that should not normally cause such sensations. Previous studies show that SSS
      could be a small fibre neuropathy, but quantitative sensory testing (QST) is
      lacking. OBJECTIVES: Using QST, to determine the presence or absence of tactile
      sensitivity disorder, mainly heat pain threshold (HPT), in patients with SSS.
      METHODS: This monocentric case-control study included 21 patients with SSS and 21
      controls. The patients underwent QST. Neuropathic pain was assessed by two
      questionnaires: the Douleur Neuropathique 4 (DN4) and the Neuropathic Pain
      Symptom Inventory (NPSI). RESULTS: Forty-two patients were included in the study.
      The HPT was significantly lower in the cases (14.5 +/- 2.8) than in the controls
      (17.8 +/- 2.5) (P < 0.001). Intermediate pain (HPT 5.0) was also significantly
      decreased in patients with SSS. The DN4 and NPSI scores were significantly higher
      in the cases than in the controls. CONCLUSIONS: The decrease in HPT in patients
      with SSS compared with controls suggests the presence of hyperalgesia, probably
      due to the damage of C-fibres. These findings, as well as the increased DN4 and
      NPSI scores, strengthen the neuronal hypothesis of SSS and are new arguments for
      consideration of SSS as small fibre neuropathy.

PMID- 30113703
TI  - Contribution of the results-based financing strategy to improving maternal and
      child health indicators in Burkina Faso.
AB  - In response to the poor performance of its public health care provision, Burkina
      Faso decided, to implement results-based financing (RBF). This strategy relies on
      a strategic purchase of the quantity and quality of services provided by health
      workers, monitored by a set of indicators. However, there is a lack of evidence
      on its effects. The objective of this article is to appreciate the effect of RBF
      on a set of maternal and child health (MCH) indicators in Burkina Faso. The study
      design is quasi-experimental comparative with a control group before and after
      the implementation of the RBF. To estimate the effect of RBF, we used two methods
      of analysis: (1) the segmented regression to measure the effect of RBF in the
      health districts (HD) implementing RBF (RBF HD) and (2) the difference-in
      difference test to estimate the effect of RBF considering the differences in mean
      between RBF HD and HD that did not implement RBF (non-RBF HD). We found among
      five indicators studied that only the postnatal consultation coverage in RBF HD
      was significantly higher (7.68%; P = 0.04) than in the non-RBF HD. Overall, our
      findings do not clearly demonstrate the effectiveness of RBF in improving MCH
      indicators in Burkina Faso.

PMID- 30113704
TI  - Total donor chimerism with bone marrow GVHD after multivisceral transplantation.

PMID- 30113702
TI  - Identification of canine cytochrome P-450s (CYPs) metabolizing the tramadol (+)
      M1 and (+)-M2 metabolites to the tramadol (+)-M5 metabolite in dog liver
      microsomes.
AB  - We previously showed that (+)-tramadol is metabolized in dog liver to (+)-M1
      exclusively by CYP2D15 and to (+)-M2 by multiple CYPs, but primarily CYP2B11.
      However, (+)-M1 and (+)-M2 are further metabolized in dogs to (+)-M5, which is
      the major metabolite found in dog plasma and urine. In this study, we identified
      canine CYPs involved in metabolizing (+)-M1 and (+)-M2 using recombinant enzymes,
      untreated dog liver microsomes (DLMs), inhibitor-treated DLMs, and DLMs from CYP
      inducer-treated dogs. A canine P-glycoprotein expressing cell line was also used
      to evaluate whether (+)-tramadol, (+)-M1, (+)-M2, or (+)-M5 are substrates of
      canine P-glycoprotein, thereby limiting their distribution into the central
      nervous system. (+)-M5 was largely formed from (+)-M1 by recombinant CYP2C21 with
      minor contributions from CYP2C41 and CYP2B11. (+)-M5 formation in DLMs from (+)
      M1 was potently inhibited by sulfaphenazole (CYP2C inhibitor) and chloramphenicol
      (CYP2B11 inhibitor) and was greatly increased in DLMs from phenobarbital-treated
      dogs. (+)-M5 was formed from (+)-M2 predominantly by CYP2D15. (+)-M5 formation
      from (+)-M1 in DLMs was potently inhibited by quinidine (CYP2D inhibitor) but had
      only a minor impact from all CYP inducers tested. Intrinsic clearance estimates
      showed over 50 times higher values for (+)-M5 formation from (+)-M2 compared with
      (+)-M1 in DLMs. This was largely attributed to the higher enzyme affinity (lower
      Km) for (+)-M2 compared with (+)-M1 as substrate. (+)-tramadol, (+)-M1, (+)-M2,
      or (+)-M5 were not p-glycoprotein substrates. This study provides a clearer
      picture of the role of individual CYPs in the complex metabolism of tramadol in
      dogs.

PMID- 30113705
TI  - The NIH's slow response to the AIDS epidemic and the dismissal of Pasteur's
      contributions: Learning from history.
AB  - The National Institutes of Health's (NIH) slow response to the AIDS epidemic in
      the early 1980s led to deaths and missed opportunities to stop the spread of the
      disease. In addition, the NIH systematically diminished the contributions of the
      scientists at the Pasteur Institute who discovered HIV and produced a superior
      AIDS test. I analyze these events by applying three social theories to the global
      response to the epidemic. Structuration, interorganizational learning, and
      negotiated order theories shed light on (1) the delay by the NIH in providing
      grants for AIDS research, (2) the inability of the NIH to learn about the
      epidemic from the Centers for Disease Control and Prevention, and (3) the NIH's
      dismissal of AIDS discoveries by a team of Pasteur scientists. Lastly, I give
      suggestions to enable effective cooperation among health agencies to better
      respond to future epidemics.

PMID- 30113707
TI  - Disasters in conflict areas: finding the politics.
AB  - Despite some 50 years of research, relatively little is known about how disasters
      in conflict areas are created and discursively framed, and how information on
      them is publicly consumed. The emphasis in disaster studies has remained on
      establishing causal linkages, demonstrating the way in which natural hazard
      related disasters result in deepening conflict, or ushering in peace.
      Furthermore, it has been accepted that disaster risk reduction is the state's
      responsibility. The strengths and limitations of these approaches are examined
      prior to a political reimagining of disasters in conflict areas. The absence of
      'politics' from the wider debate on disasters in conflict areas is not just a
      benign oversight, but is in fact the politics of disasters in conflict areas. A
      politics that does not engage with the processes and outcomes of pursuing
      dominant agendas, such as neoliberal orthodoxy and state imperial control, in
      areas and communities vulnerable to natural hazards and political conflict needs
      to be recognised and challenged.

PMID- 30113706
TI  - Flare of Autoimmune Hepatitis causing acute on chronic liver failure (ACLF):
      diagnosis and response to corticosteroid therapy.
AB  - BACKGROUND: Autoimmune hepatitis (AIH) is considered less common in the Asian
      pacific region. Due to this, AIH flare as a cause of acute on chronic liver
      failure(ACLF) is often overlooked and treatment is delayed. We aimed at defining
      clinical, histopathological spectrum and role of steroid therapy in AIH-ACLF.
      PATIENTS AND METHODS: Patients with AIH-ACLF, prospectively recruited and
      followed between 2012-2017, were analyzed from the APASL ACLF Research Consortium
      (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune
      Hepatitis Group (IAIHG) score or simplified AIH score with histopathological
      evidence. RESULTS: Of 2,825 ACLF patients, 82(2.9%) fulfilled criteria of AIH
      (age 42.1+/-18.1yr, 70%females). At baseline, mean bilirubin was 18.6+/-8.2mg/dl,
      CTP score 11.7+/-1.4 and MELD score 27.6+/-6.5. Mean IgG was 21.61+/-7.32 g/dl
      and was elevated >=1.1 times in 97%; 49% were seronegative. Liver histology was
      available in 90%, with median HAI of 10[IQR:7-12]; 90%with moderate to severe
      interface activity; 56% showing significant parenchymal necrosis (bridging and
      confluent necrosis) and cirrhosis in 42%. Twenty eight (34%) patients received
      steroid therapy, and showed shorter ICU stay (median 1.5Vs.4 day; p<0.001),
      improved 90 day survival (75%Vs.48.1%; p=0.02) with comparable incidence of
      sepsis (p=0.32) compared to those who did not. Patients of advanced age, more
      severe liver disease (MELD > 27; 83.3% sensitivity, 78.9% specificity, AUROC
      0.86), presence of hepatic encephalopathy and fibrosis grade >= F3, had an
      unfavourable response to corticosteroid therapy. CONCLUSIONS: AIH presenting as
      ACLF is not uncommon in Asian patients. A low threshold for liver biopsy is
      needed to confirm the diagnosis as nearly half the patients are seronegative.
      Early stratification to steroid therapy or liver transplantation (MELD>27; HE in
      >= F3) would reduce ICU stay and improve outcomes. This article is protected by
      copyright. All rights reserved.

PMID- 30113708
TI  - Population-based outcome analysis of diffuse large B-cell lymphoma in people
      living with HIV infection and competent individuals.
AB  - The prognostic factors and outcome of 58 acquired immunodeficiency syndrome
      related diffuse large B-cell lymphoma (AR-DLBCL) patients from the Swiss HIV
      Cohort Study, diagnosed from 2004 to 2011, were compared with those of 326
      immunocompetent (IC)-DLBCL from the Hematology Division of the Amedeo Avogadro
      University (Italy) and the Oncology Institute of Southern Switzerland. Median
      follow-up was 6 years; 5-year overall survival (OS) was 68% (95% CI: 63%-73%) in
      IC-DLBCL and 63% (95% CI: 49%-75%) in AR-DLBCL (P = .220). The acquired
      immunodeficiency syndrome-related lymphoma international prognostic index
      predicted OS in AR-DLBCL. Among 148 patients younger than 61 years (40 AR-DLBCL
      and 108 IC-DLBCL) treated with RCHOP/RCHOP-like regimens, 20 IC-DLBCL and 9 AR
      DLBCL patients died and OS was not significantly different. A higher proportion
      of early deaths occurred in the AR-DLBCL: indeed, 1-year OS was 94% (95% CI: 87%
      97%) in IC-DLBCL and 82% (95% CI: 66%-91%) in AR-DLBCL patients. After rituximab
      and active antiretroviral therapy introduction, AR-DLBCL and IC-DLBCL patients
      treated with curative intent have similar long-term survival.

PMID- 30113709
TI  - Administrative databases and clinical governance: The case of COPD.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of
      morbidity and mortality worldwide. However, COPD is still underdiagnosed,
      undertreated, and not sufficiently prevented. Health administrative databases
      provide a powerful way of studying COPD in the population. METHODS: This
      retrospective study used administrative data, collected during 2011 and 2012,
      retrieved from 3 Italian local health authorities (LHAs). RESULTS: The analysis
      through administrative databases allowed firstly to identify patients with COPD
      receiving services by the 3 LHAs: The estimated average is ~3% of the population
      aged >=40 years. Furthermore, it was also possible to stratify patients by
      investigating the health consumption in hospitalization for COPD and use of
      respiratory drugs. In all 3 LHA patients with moderate COPD were the majority of
      the population with COPD. Finally, it was possible to distinguish patients who
      made an appropriate use of SABA (76% of the total), patients who had a
      potentially inappropriate use (20%), and those with an overuse of SABA (4%).
      CONCLUSION: The use of SABA consumption patterns can be a reliable proxy variable
      to detect subgroups who may necessitate therapy revision. Health administrative
      databases seem beneficial for planning health care interventions, including the
      COPD field. They are robust information systems subjected to regular data quality
      controls remaining the prevalent data source, reliable because of the amount of
      data and the population coverage, especially in countries with a National Health
      Service System.

PMID- 30113710
TI  - Disasters, climate change, and securitisation: the United Nations Security
      Council and the United Kingdom's security policy.
AB  - Since climate change was included on the United Nations Security Council's agenda
      in 2007, there has been much debate about whether or not it has been securitised.
      This paper starts from the premise that climate change has undergone a partial
      securitisation-that is, a gradual process wherein political choices are made to
      frame certain issues in particular ways. Climate change has been reframed from a
      purely developmental and environmental concern to one that impels foreign policy
      and security domains. This paper makes a novel contribution to disasters, climate
      change, and security studies by arguing that explicit and implicit links to
      natural hazard-related disasters have been employed as part of a gradual process
      of securitisation, or, more specifically, the partial securitisation of climate
      change. This is demonstrated by drawing on two cases: United Nations Security
      Council debates between 2007 and 2017; and the United Kingdom's security policy
      between 1997 and 2017.

PMID- 30113711
TI  - Characterization of Maternal and Neonatal Pharmacokinetic Behavior of
      Ceftazidime.
AB  - Ceftazidime is a parenteral cephalosporin frequently used in pregnant women for
      treatment of urinary tract or intrauterine infections. Despite its regular use in
      pregnant women, ceftazidime disposition in both mother and fetus is not well
      understood, and a pharmacokinetic (PK) model that allows characterization and
      simulation of both maternal and preterm neonatal ceftazidime disposition is not
      available. In this study, 10 pregnant women with suspected or proven intrauterine
      infections in the late second and early third trimester were treated with 1 g of
      ceftazidime intravenously every 6 hours. During ceftazidime treatment, one
      maternal and umbilical cord blood sample was taken at delivery to quantify
      ceftazidime concentrations in the mother and preterm neonate. Data showed that
      ceftazidime concentrations in the mother were comparable to those observed in the
      neonate. Based on these data, a PK model was developed to describe maternal
      disposition, ceftazidime distribution over the placenta, and elimination in the
      neonate. The maternal substructure of the model was parameterized according to a
      previously reported ceftazidime model with minor adjustments to account for
      pregnancy-related effects on renal elimination of ceftazidime. The expanded
      population PK model with an additional neonatal compartment was fitted to
      measured drug concentrations in the neonate. The neonatal elimination rate
      constant at delivery was close to that estimated for the mother. The presented
      results show that ceftazidime readily crosses the placenta and indicate that
      perinatal PK behavior of ceftazidime in preterm neonates can be expected to be
      similar to those observed in their mothers.

PMID- 30113712
TI  - Disaster risk reduction amidst armed conflict: informal institutions, rebel
      groups, and wartime political orders.
AB  - Extant research has explored the effect of natural hazards on the risk of armed
      conflict, but very few studies have examined how conflict dynamics affect
      disaster risk reduction (DRR), including climate change adaptation. This is
      surprising given the empirical evidence that indicates how often disasters and
      armed conflicts collide. To understand better the impact of armed conflict on
      DRR, this paper develops a conceptual typology that is based on rebel groups'
      territorial control and on the strength of informal institutions. It documents
      three main political orders amid conflict: rebel stability; informal stability;
      and fragmented landscape. These wartime political orders will have different
      effects on DRR and other development programmes, revealing the importance of
      desegregating armed conflict to facilitate tailor-made and more efficient
      interventions. The paper provides empirical evidence from Mali and the
      Philippines that illustrates the influence of these wartime political orders on
      DRR programmes.

PMID- 30113713
TI  - Stories from the frontlines: decolonising social contracts for disasters.
AB  - Disasters are framed as political moments when states are unable to provide
      security to their citizens, causing disruption and a possible 'break' in the
      state-citizen social contract. Evidence from the frontlines of insurgency and
      secessionist movements in southern Philippines suggests that social contracts do
      not 'break' in this manner, despite widespread suffering during a complex event.
      This paper presents new perspectives on social contracts after disasters, in
      conflict-affected regions. Using ethnographic data from two case studies in the
      Philippines, it argues that disasters in conflict-affected areas do not manifest
      a 'break' in social contracts in ways that result in 'state failure' and
      'insurgent capture'. Instead, it shows that the state-citizen contract is a
      dynamic contestation of state responsibilities, while also being malleably
      resilient. The inequalities and anxieties prevalent in social contracts are
      reproduced in the highly differentiated experiences of 'disaster citizenship' for
      people living amidst conflict.

PMID- 30113714
TI  - Management of physical pain during induced second-trimester medical abortions: a
      cross-sectional study of methodological quality and recommendations in local
      clinical practice guidelines at Swedish hospitals.
AB  - AIM: The aim was to assess the methodological quality and describe
      recommendations for pain management in local clinical practice guidelines about
      induced second-trimester medical abortions at Swedish university and county
      hospitals. METHODS: In 2017, Swedish university and county hospitals that
      provided abortion care in the second trimester of pregnancy were contacted (n =
      29), and guidelines from 25 were received (university: n = 6, county: n = 19).
      Guideline quality was assessed according to two systematic instruments.
      Recommendations were systematically assessed regarding frequency and tools for
      pain measurement, prophylactic pharmacologic treatment, as needed pharmacologic
      treatment and nonpharmacologic treatment. RESULTS: Overall methodological quality
      was poor across both instruments, as the majority of the guidelines did not
      fulfil the investigated quality criteria. For pain measurements, no guideline
      recommended measurement frequency and four recommended specific measurement
      tools. Prophylactic pharmacologic treatment, described in 23 (92%) guidelines,
      included paracetamol (n = 23, 92%), anti-inflammatory drugs (n = 23, 92%) and
      opioids (n = 18, 72%). As needed pharmacologic treatment, described in 23 (92%)
      guidelines, included anaesthetics (n = 21, 84%), opioids (n = 21, 84%) and
      paracetamol (n = 1, 4%). Recommendations for as needed anaesthetics included
      paracervical block (n = 21, 84%), epidural analgesia (n = 16, 64%) and inhalation
      of nitrous oxide (n = 5, 20%). Nonpharmacologic treatments were recommended in
      nine (36%) guidelines. CONCLUSIONS: The findings indicate that local clinical
      practice guidelines about induced second-trimester medical abortions are of
      inadequate methodological quality and that a large majority lack recommendations
      concerning systematic pain measurements. Although most recommend prophylactic and
      as needed pharmacologic management, national inconsistencies exist in Sweden with
      regard to recommendations of epidural analgesia, nitrous oxide and
      nonpharmacologic methods. In Sweden, there is room for improvement in the
      development of these guidelines.

PMID- 30113715
TI  - Equivocal (HER2 IHC 2+) breast carcinomas: gene-protein assay testing reveals
      association between genetic heterogeneity, individual cell amplification status
      and potential treatment benefits.
AB  - AIMS: Genetic heterogeneity can pose a challenge to identifying eligible cases
      for targeted therapy in the human epidermal growth factor receptor 2 (HER2)
      immunohistochemistry (IHC) 2+ breast carcinoma group. In this study, we
      characterised this subset of tumours according to clinicopathological parameters.
      METHODS AND RESULTS: We assessed 1000 tumour cells per case and recorded the
      number of HER2 and chromosome enumeration probe 17 (CEP17) copies using gene
      protein assay slides. HER2 status was determined based on ASCO/CAP 2013
      guidelines. Tumours with 5-50% of cancer cells with amplification were considered
      to be heterogeneous, whereas those with >50% were considered to be non
      heterogeneous. In a study cohort of 110 HER2 IHC 2+ carcinomas, 93 (84.5%) were
      non-amplified, 12 (10.9%) were amplified and five (4.5%) were ISH-equivocal. All
      the HER2-amplified and two of ISH-equivocal cases (12.7%) corresponded to non
      heterogeneous tumours, with highly significant differences evident in the average
      HER2/CEP17 ratio (P = 0.0002) and the proportion of cells with HER2 >6 copies (P
      < 0.0001) compared with heterogeneous lesions. NST grade 3 and HER2-amplified
      carcinomas average HER2/CEP17 ratio correlated with an increased number of cells
      with HER2/CEP17 >=2.0 (P < 0.014). Triple-negative CEP17 polysomic carcinomas
      showed increased metastatic capacity (P = 0.003) compared with other tumour
      types. CONCLUSION: Non-heterogeneous HER2 IHC 2+ tumours tend to be HER2
      amplified. Adding the percentage of cells with HER2 >6 copies to the average
      HER2/CEP17 ratio may facilitate assessment of amplification status in ISH
      equivocal cases. The proportion of cells with HER2/CEP17 >=2.0 contributes
      information concerning the actual average HER2/CEP17 ratio, depending on tumour
      type.

PMID- 30113716
TI  - 3-(7-Azaindolyl)-4-indolylmaleimides as a novel class of mutant isocitrate
      dehydrogenase-1 inhibitors: Design, synthesis, and biological evaluation.
AB  - A series of 3-(7-azainodyl)-4-indolylmaleimides was designed, synthesized, and
      evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory
      activities. Many compounds such as 11a, 11c, 11e, 11g, and 11s exhibited
      favorable inhibitory effects on IDH1/R132H and were highly selective against the
      wild-type IDH1. Evaluation of the biological activities at the cellular level
      showed that compounds 11a, 11c, 11e, 11g, and 11s could effectively suppress the
      production of 2-hydroxyglutaric acid in U87MG cells expressing IDH1/R132H.
      Preliminary structure-activity relationship (SAR) and molecular modeling studies
      were discussed based on the experimental data obtained. These findings may
      provide new insights into the development of novel IDH1/R132H inhibitors.

PMID- 30113717
TI  - Emergency patients' and family members' experiences of encountering care
      providers and receiving care in nonconveyance situations.
AB  - BACKGROUND: Not much research has been conducted on emergency patients' and
      family members' experiences of encountering care providers and receiving care in
      nonconveyance situations. This knowledge is required to develop the quality and
      safety of emergency care. AIM: The aim of the study was to describe patients' and
      family members' experiences concerning encounters with emergency care providers
      and the patient's care in nonconveyance situations. METHODS: The study is a
      descriptive, cross-sectional survey carried out using quantitative methods.
      Statistical data were analysed using SPSS Statistics for Windows. The responses
      to an open question were analysed using inductive content analysis. RESULTS:
      Patients and family members found that emergency care providers had acted in a
      professional and friendly manner. They would have expected more psychological
      support. Family members were less satisfied with the emergency care than
      patients, especially as regards psychological support and the amount of time
      given to the patient. CONCLUSIONS: Emergency care providers should take the whole
      family's situation into consideration and seek to promote the family's coping by
      providing comprehensible counselling and support.

PMID- 30113719
TI  - Corrigendum to "Polyethylene glycol solutions rapidly restore and maintain axonal
      continuity, neuromuscular structures, and behaviors lost after sciatic nerve
      transections in female rats."

PMID- 30113720
TI  - Brain architecture at varying scales.

PMID- 30113718
TI  - Altered anabolic signalling and reduced stimulation of myofibrillar protein
      synthesis after feeding and resistance exercise in people with obesity.
AB  - KEY POINTS: Lifestyle modifications that include the regular performance of
      exercise are probably important for counteracting the negative consequences of
      obesity on postprandial myofibrillar protein synthetic responses to protein dense
      food ingestion. We show that the interactive effect of resistance exercise and
      feeding on the stimulation of myofibrillar protein synthesis rates is diminished
      with obesity compared to normal weight adults. The blunted myofibrillar protein
      synthetic response with resistance exercise in people with obesity may be
      underpinned by alterations in muscle anabolic signalling phosphorylation (p70S6K
      and 4E-BP1). The results obtained in the present study suggest that further
      exercise prescription manipulation may be necessary to optimize post-exercise
      myofibrillar protein synthesis rates in adults with obesity. ABSTRACT: We aimed
      to determine whether obesity alters muscle anabolic and inflammatory signalling
      phosphorylation and also muscle protein synthesis within the myofibrillar (MYO)
      and sarcoplasmic (SARC) protein fractions after resistance exercise. Nine normal
      weight (NW) (21 +/- 1 years, body mass index 22 +/- 1 kg m-2 ) and nine obese
      (OB) (22 +/- 1 years, body mass index 36 +/- 2 kg m-2 ) adults received l-[ring
      13 C6 ]phenylalanine infusions with blood and muscle sampling at basal and fed
      state of the exercise (EX) and non-exercise (CON) legs. Participants performed
      unilateral leg extensions and consumed pork (36 g of protein) immediately after
      exercise. Basal muscle Toll-like receptor 4 (TLR4) protein was similar between OB
      and NW groups (P > 0.05) but increased at 300 min after pork ingestion only in
      the OB group (P = 0.03). Resistance exercise reduced TLR4 protein in the OB group
      at 300 min (EX vs. CON leg in OB: P = 0.04). Pork ingestion increased p70S6K
      phosphorylation at 300 min in CON and EX of the OB and NW groups (P > 0.05),
      although the response was lower in the EX leg of OB vs. NW at 300 min (P = 0.05).
      Basal MYO was similar between the NW and OB groups (P > 0.05) and was stimulated
      by pork ingestion in the EX and CON legs in both groups (Delta from basal NW: CON
      0.04 +/- 0.01% h-1 ; EX 0.10 +/- 0.02% h-1 ; OB: CON 0.06 +/- 0.01% h-1 ; EX 0.06
      +/- 0.01% h-1 ; P < 0.05). MYO was more strongly stimulated in the EX vs. CON
      legs in NW (P = 0.02) but not OB (P = 0.26). SARC was feeding sensitive but not
      further potentiated by resistance exercise in both groups. Our results suggest
      that obesity may attenuate the effectiveness of resistance exercise to augment
      fed-state MYO.

PMID- 30113721
TI  - Brain structural changes associated with aberrant functional responses to the
      Valsalva maneuver in heart failure.
AB  - Heart failure (HF) patients show inability to regulate autonomic functions in
      response to autonomic challenges. The autonomic deficits may stem from brain
      tissue injury in central autonomic regulatory areas, resulting from ischemic and
      hypoxic processes accompanying the condition. However, the direct evaluation of
      correlations between brain structural injury and functional timing and magnitude
      of neural signal patterns within affected areas, which may lead to impaired
      autonomic outflow, is unclear. In this study, we evaluate neural responses to the
      Valsalva maneuver with blood oxygen level-dependent functional magnetic resonance
      imaging in 29 HF patients and 35 control subjects and brain structural changes
      using diffusion tensor imaging-based mean diffusivity in a subsample of 19 HF and
      24 control subjects. HF showed decreased neural activation in multiple autonomic
      and motor control areas, including cerebellum cortices, vermis, left insular,
      left putamen, and bilateral postcentral gyrus. Structural brain changes emerged
      in similar autonomic, as well as cognitive and mood regulation areas. Functional
      MRI responses in cerebellum and insula in HF subjects are delayed or decreased in
      magnitude to the challenge. The impaired functional responses of insular and
      cerebellar sites are correlated with the severity of tissue changes. These
      results indicate that the functions of insular and cerebellar regions, sites that
      are involved in autonomic regulation, are compromised, and that autonomic
      deficits in these areas have brain structural basis for impaired functions. Our
      study enhanced our understanding of brain structural and functional alterations
      underlying impaired autonomic regulations in HF subjects.

PMID- 30113723
TI  - Corrigendum to "Polyethylene glycol treated allografts not tissue matched nor
      immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular
      functions, and restore voluntary behaviors in female rats".

PMID- 30113722
TI  - Purkinje cell COX deficiency and mtDNA depletion in an animal model of
      spinocerebellar ataxia type 1.
AB  - Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of
      cerebellar degenerative disorders, characterized by progressive gait
      unsteadiness, hand incoordination, and dysarthria. Ataxia type 1 (SCA1) is caused
      by the expansion of a CAG trinucleotide repeat in the SCA1 gene resulting in the
      atypical extension of a polyglutamine (polyQ) tract within the ataxin-1 protein.
      Our main objective was to investigate the mitochondrial oxidative metabolism in
      the cerebellum of transgenic SCA1 mice. SCA1 transgenic mice develop clinical
      features in the early life stages (around 5 weeks of age) presenting pathological
      cerebellar signs with concomitant progressive Purkinje neuron atrophy and
      relatively little cell loss; this evidence suggests that the SCA1 phenotype is
      not the result of cell death per se, but a possible effect of cellular
      dysfunction that occurs before neuronal demise. We studied the mitochondrial
      oxidative metabolism in cerebellar cells from both homozygous and heterozygous
      transgenic SCA1 mice, aged 2 and 6 months. Histochemical examination showed a
      cytochrome-c-oxidase (COX) deficiency in the Purkinje cells (PCs) of both
      heterozygous and homozygous mice, the oxidative defect being more prominent in
      older mice, in which the percentage of COX-deficient PC was up to 30%. Using a
      laser-microdissector, we evaluated the mitochondrial DNA (mtDNA) content on
      selectively isolated COX-competent and COX-deficient PC by quantitative
      Polymerase Chain Reaction and we found mtDNA depletion in those with oxidative
      dysfunction. In conclusion, the selective oxidative metabolism defect observed in
      neuronal PC expressing mutant ataxin occurs as early as 8 weeks of age thus
      representing an early step in the PC degeneration process in SCA1 disease.

PMID- 30113724
TI  - Safety, Pharmacokinetics, and Pharmacodynamics of Multiple Rising Doses of BI
      655064, an Antagonistic Anti-CD40 Antibody, in Healthy Subjects: A Potential
      Novel Treatment for Autoimmune Diseases.
AB  - BI 655064 is a humanized antagonistic anti-cluster of differentiation (CD) 40
      monoclonal antibody that selectively blocks the CD40-CD40L interaction. The CD40
      CD40L pathway is a promising treatment target for autoimmune diseases such as
      rheumatoid arthritis, systemic lupus erythematosus, and lupus nephritis. The
      safety, tolerability, pharmacokinetics, and pharmacodynamics of repeated once
      weekly BI 655064 subcutaneous dosing over 4 weeks were evaluated in a multiple
      dose study in healthy subjects. Subjects (N = 40) were randomized 4:1 to four
      sequential BI 655064 dose groups (80, 120, 180, 240 mg) or to placebo. Safety and
      tolerability, plasma exposure, CD40 receptor occupancy, and CD40L-induced CD54
      upregulation were assessed over 64 and 78 days for the 80- to 180-mg and 240-mg
      dose groups, respectively. BI 655064 exposure increased in a supraproportional
      manner, due to target-mediated drug clearance, for doses between 80 mg and 120
      mg, but was near proportional for doses greater than 120 mg. Terminal half-life
      ranged between 6 and 8 days. Dose-dependent accumulation of BI 655064 supports
      the use of a loading dose in future clinical studies. Following 4 weeks of
      dosing, >90% CD40 receptor occupancy and inhibition of CD54 upregulation were
      observed at all dose levels, lasting for 17 days after the last dose. BI 655064
      was generally well tolerated. There were no serious adverse events and the
      frequency and intensity of adverse events were similar for BI 655064 and placebo;
      no dose relationship or relevant signs of an acute immune reaction were observed.
      These findings support further investigation of BI 655064 as a potential
      treatment for autoimmune diseases.

PMID- 30113725
TI  - Are health care facilities and programs in Western Uganda encouraging or
      discouraging men's participation in maternal and child health care?
AB  - INTRODUCTION: In patriarchal communities, men are in control of health care
      decisions of their families. As spouses, their health status impacts on the
      health of their partners and children as well. The participation of men in
      maternal and child health (MCH) is thus crucial for the reduction of infant and
      maternal mortality, as spouses and parents. Hence, the government of Uganda has
      been encouraging male participation in MCH, and healthy facilities have been
      mandated to implement mandatory male participatory programs such as in antenatal
      care among others. Despite these initiatives, health facilities and programs have
      been failing the government's vision. METHODS: The study was done in Muko Health
      Center IV and Mparo Health Center IV, Kabale District in Western Uganda. Case
      study approach was used with the application of questionnaires, in-depth
      interviews, document analysis, observation, and focus group discussions. RESULTS:
      Men relatively participate in programs that have services they can consume as
      health seekers mostly reproductive health programs such as family planning,
      prevention of mother-to-child transmissions, and elimination of mother-to-child
      transmission. Low participation of men in MCH was attributed to institutional and
      health facility challenges such as feminization of health messages, inadequate
      structures, unfriendly health workers, and social cultural factors. CONCLUSION:
      Male participation in MCH leaves a lot to be desired. Health facilities and
      structures are neither conducive nor encouraging participation. Therefore, health
      institutions should design innovative strategies mainstreaming male involvement
      in line with development trends as well as enhance ethics and integrity among
      health care workers.

PMID- 30113726
TI  - Ultrasound hyperthermia enhances chemo-sensitivity in oral squamous cell
      carcinoma by TRIF-mediated pathway.
AB  - BACKGROUND: Hyperthermia is currently used as an alternative to surgery or in
      combination with chemotherapy and/or radiation therapy in the treatment of oral
      squamous cell carcinoma. However, little has been known about the change in chemo
      sensitivity after hyperthermia and the mechanism underlie it in oral squamous
      cell carcinoma. METHODS: The aim of this study was to explore the influence of
      chemo-sensitivity of CAL-27 and SCC-4 cells by histoculture drug response assay
      after the animal model treated by the ultrasound hyperthermia. Then, we conducted
      a microarray between xenograft after hyperthermia at 42 degrees C for 45 minutes
      and that with no treatment. We further confirmed the expression of TRIF in
      hyperthermia by immunohistochemistry, RT-PCR and Western blot. RESULTS: The chemo
      sensitivity to five kinds of drugs demonstrated ultrasound hyperthermia performed
      in 42 degrees C for 45 minutes would reach the highest inhibition rate in CAL-27
      and SCC-4 cells. The microarray dataset revealed that 847 mRNA were upregulated
      and 1031 were downregulated. GO and pathway analyses indicated that they play an
      important role in translational initiation, nucleoplasm, and poly (A) RNA binding
      in the hyperthermia process. We further confirmed the expression of TRIF was
      downregulated in hyperthermia along with inactivation of NF-kappaB pathway.
      CONCLUSIONS: The experiments confirms the rationality of synchronous combination
      of hyperthermia and chemotherapy and may provide a better treatment that the use
      of sensitivity testing in such cases may lead to individualized, more effective
      therapy.

PMID- 30113728
TI  - Out-of-pocket expenditure for health care: District level estimates for Haryana
      state in India.
AB  - INTRODUCTION: In this paper, we present district level out-of-pocket (OOP)
      expenditures with respect to outpatient consultation within last 15 days and
      hospitalization in last 1 year for Haryana state. METHODS: The data from a large
      cross-sectional household survey covering all 21 districts of Haryana comprising
      of randomly selected 79 742 households were analyzed. Of the total sample, 56 056
      households consisting of 314 639 individuals in 21 districts of Haryana state
      were surveyed to gather information on OOP expenditure incurred on outpatient
      consultation within last 15 days. Similarly, 59 901 households and 324 977
      respondents were interviewed to elicit OOP expenditures for any hospitalization
      during the 1 year preceding the survey. Mean OOP expenditure per OP consultation,
      per hospitalization as well as per capita were computed. Mean OOP expenditure was
      also estimated by the type of provider, gender, and district. RESULTS: The mean
      OOP expenditure for OP consultation and hospitalization in Haryana was Indian
      National Rupees (INR) 1005 (US Dollar [USD] 16.1; 95% CI: INR 934-1076) and INR
      22 489 (USD 360.0; 95% CI: INR 21 375-23 608), respectively. Mean per capita OOP
      expenditure for OP consultation, which was INR 85 (USD 1.3) in Haryana, varied
      from INR 595 (USD 9.5) in district Panipat to INR 29 (USD 0.5) in district
      Kaithal. CONCLUSION: This is the first study to comprehensively present district
      level estimates for OOP expenditure for health care. These estimates are useful
      for policy planning, and preparation for district and state health accounts.

PMID- 30113727
TI  - Biodiversity loss along a gradient of deforestation in Amazonian agricultural
      landscapes.
AB  - Assessing how much management of agricultural landscapes, in addition to
      protected areas, can offset biodiversity erosion in the tropics is a central
      issue for conservation that still requires cross-taxonomic and landscape-scale
      studies. We measured the effects of Amazonia deforestation and subsequent land
      use intensification in 6 agricultural areas (landscape scale), where we sampled
      plants and 4 animal groups (birds, earthworms, fruit flies, and moths). We
      assessed land-use intensification with a synthetic index based on landscape
      metrics (total area and relative percentages of land uses, edge density, mean
      patch density and diversity, and fractal structures at 5 dates from 1990 to
      2007). Species richness decreased consistently as agricultural intensification
      increased despite slight differences in the responses of sampled groups.
      Globally, in moderately deforested landscapes species richness was relatively
      stable, and there was a clear threshold in biodiversity loss midway along the
      intensification gradient, mainly linked to a drop in forest cover and quality.
      Our results suggest anthropogenic landscapes with high-quality forest covering
      >40 % of the surface area may prevent biodiversity loss in Amazonia.

PMID- 30113729
TI  - GIS-based method to delimit spheres of influence for a medical consortium:
      Experience of a pediatric medical consortium, Shanghai.
AB  - BACKGROUND: To improve the utilization efficiency of health care services, the
      concept of a "regional medical consortium" has attracted more attention during
      the most recent round of health care reform in China. Shanghai, a municipality of
      China, has made many efforts to promote its regional medical consortium project.
      In this paper, the pediatric medical consortium of Shanghai will serve as an
      example to introduce the main tasks and groundwork of the Shanghai medical
      consortium and will underscore Shanghai's exploration of the vertical integration
      of medical resources. METHODS: This study delimits the service areas of leading
      hospitals, which can help determine the spheres of influence of top hospitals
      geographically. With this information, regional hospitals or community hospitals
      can find alliance hospitals and leading hospitals more easily. These efforts can
      be realized using ArcGIS for spatial data analysis. RESULTS: According to the
      locations of leading hospitals and actual patient distributions at these
      hospitals, the natural areas of influence of leading hospitals are illustrated.
      Then, hospitals other than leading hospitals can select allied hospitals in the
      same area of influence. In this way, connections in a medical consortium will be
      tighter, and hospitals will be better able to meet the actual demands of
      patients. CONCLUSIONS: In this paper, we introduce a geographic method to delimit
      the spheres of influence of hospitals based on actual health-seeking behaviors of
      patients by analyzing the spatial distribution of hospitalization probability.
      Within the boundaries of a sphere of influence, a geographic connection between
      the leading hospital and the general hospital is established automatically. Based
      on this geographic connection, leading hospitals should provide technological
      support to general hospitals located in their sphere of influence, while the
      general hospitals should provide spare medical resources in return. Thus, the
      medical consortium can be formed geographically and operate more smoothly.

PMID- 30113730
TI  - All-Inorganic Perovskite CsSnBr3 as a Thermally Stable, Free-Carrier
      Semiconductor.
AB  - Hybrid organic-inorganic perovskites, especially methylammonium lead triiodide
      (MAPbI3 ), are intensely studied for their optoelectronic properties. The organic
      MA+ cation is held responsible for the superior performance of MAPbI3 but also
      its instability toward moisture and heat. To explore compositions beyond MAPbI3 ,
      we performed experiments and calculations on two isomorphous perovskites CsSnBr3
      and MASnBr3 . CsSnBr3 is slightly smaller than MASnBr3 in cell dimension, but
      outperforms MASnBr3 in band gap energy, charge-carrier reduced effective mass,
      and optical dielectric constant all by ~19 %. These merits accumulate to
      drastically cut the exciton binding energy from 33 meV for MASnBr3 to 19.6 meV
      for CsSnBr3 , making CsSnBr3 a black, free-carrier semiconductor. CsSnBr3 also
      exhibits distinctly higher stability toward moisture and heat than its organic
      counterparts. These advantages suggest ecofriendly applications for CsSnBr3 ,
      such as tandem solar cells and direct X-ray detectors.

PMID- 30113731
TI  - Unique Supramolecular Liquid-Crystal Phases with Different Two-Dimensional
      Crystal Layers.
AB  - We report herein a series of tetrablock-mimic azobenzene-containing [60]fullerene
      dyads that form supramolecular liquid crystals (LCs) from phase-segregated two
      dimensional (2D) crystals. The unique double-, triple-, and quadruple-layer
      packing structure of fullerenes in the 2D crystals leads to different smectic
      supramolecular LC phases, and novel LC phase transitions were observed upon
      changes in the fullerene packing layer number in the 2D crystals. Interestingly,
      by combining the LC properties with 2D crystals, these materials show excellent
      electron mobility in the order of 10-3  cm2  V-1  s-1 , despite their relatively
      low fullerene content. Our results provide a novel method to manipulate 2D
      crystal layer thickness, with promising applications in optoelectronic devices.

PMID- 30113732
TI  - Optimization of the 2014 Gleason grade grouping in a Canadian cohort of patients
      with localized prostate cancer.
AB  - OBJECTIVES: To evaluate the five-tier Gleason grade group (GG) scoring of
      prostate cancers adopted by the International Society of Urology Pathology (ISUP)
      in 2014, and to propose modifications to optimize its performance. PATIENTS AND
      METHODS: Data were obtained from PROCURE, a prospective cohort of patients with
      localized prostate cancer undergoing radical prostatectomy in Quebec, 2006-2013.
      Surgical specimens were evaluated by genitourinary pathologists using 2014 ISUP
      criteria. Treatment failure was defined as biochemical recurrence and/or
      initiation of secondary, non-adjuvant therapy. Analyses were conducted using
      Kaplan-Meier methods, log-rank tests, Cox proportional hazards models and
      Harrell's concordance indices. RESULTS: A total of 1 917 patients were included,
      with a median follow-up of 69 months. The 5-year treatment failure rates were
      9.6%, 23.5%, 43.1%, 52.6% and 84.3% in GG1-5, respectively (P < 0.001 when
      comparing GG2 with GG3). Treatment failure rates for patients in GG2 and GG3 with
      tertiary Gleason 5 pattern were higher than patients in the same group without a
      tertiary pattern (P < 0.001), but were similar to rates for patients in GGs 3 or
      4 without a tertiary pattern (P > 0.3). Primary Gleason pattern (4/5) predicted
      treatment failure in GG5 (5-year failure rates 82.3% vs 97.1%, respectively; P =
      0.001). The five-tier GG system had greater accuracy as a prognostic indicator
      compared with the four-tier system (Harrell's concordance index 0.716 vs 0.676).
      When upgrading patients in GG2/3 with tertiary Gleason 5 pattern to patients in
      GG3/4, and separating patients in GG5 by primary Gleason pattern, the Harrell's
      concordance index increased to 0.730. CONCLUSION: The five-tier GG system
      increased accuracy for predicting treatment failure compared with the previous
      grading systems, but can be further improved.

PMID- 30113733
TI  - Mixed-methods content and sentiment analysis of adolescents' voice diaries
      describing daily experiences with asthma and self-management decision-making.
AB  - BACKGROUND: Accurate symptom assessment remains challenging in teen populations.
      Little is known of usual symptom/response patterns, and self-reported paper
      diaries have traditionally low compliance rates. Therefore, we used concurrent
      digital voice diaries to capture daily asthma experiences. OBJECTIVE: (a) To
      qualitatively explore usual symptom patterns and self-management responses and
      (b) to quantitatively explore relationships between symptom severity and
      sentiment scores (a marker of emotional response to events). METHODS: Fourteen
      minority and nonminority teenagers (age 13-17) with controlled (50%) and
      uncontrolled asthma used digital recorders to report about their asthma once
      daily over 14 days. Dairy entries were coded for symptom frequency, severity,
      type, and self-management responses, while sentiment analysis was used to
      evaluate the emotional valence of diary entries and to explore whether increased
      symptom levels correlated with greater negative sentiment. RESULTS: Symptom
      frequency and severity recorded in voice diaries were much higher than teens
      indicated at baseline and were discordant with clinical assessments of asthma
      control. Of 175 entries, teens had symptoms 69.1% of days (121/175) and severe
      symptoms on one-third of these. Atypical symptoms (coughing, throat clearing)
      were reported twice as often as traditional symptoms (wheezing, chest tightness)
      and often not recognized as asthma, but rather attributed to being "sick" (25.6%
      of symptom days). Teens frequently minimized symptoms, used rescue and controller
      medication inconsistently, and resorted to alternative strategies to manage
      symptoms. Sentiment was not significantly correlated with assessed control (beta
      = 0.14, P = 0.28), but for teens reporting severe symptoms, sentiment scores
      decreased by 0.31 relative to teens without symptoms (P = 0.006). CONCLUSIONS AND
      CLINICAL RELEVANCE: Teens may minimize symptoms and have greater symptom
      frequency and severity than is recognized by themselves or providers. Screening
      for specific symptoms including coughing, throat clearing, and respiratory
      illness may be needed to identify those experiencing burden from asthma.

PMID- 30113734
TI  - Quantitative analysis of apically extruded bacteria following preparation of
      curved canals with three systems.
AB  - This study compared the amount of apically extruded bacteria following
      preparation of curved root canals using two continuously rotating multifile and
      one reciprocating single-file systems. Mesiobuccal canals from maxillary molars
      were contaminated with Enterococcus faecalis and divided into three groups
      according to the instrumentation system: Reciproc (R25 instrument, 25/.08), BT
      RaCe (10/.06, 35/.00 and 35/.04), and Mtwo (25/.06, 30/.05 and 35/.04). Apically
      extruded material was collected by a customized apparatus with 1.5% agarose gel
      covering the root apex to simulate the periradicular tissues. The extruded
      material was extracted from the gel and subjected to bacteriological culture for
      bacterial quantification. The three systems showed a high frequency of bacterial
      extrusion (>70%). There were no statistically significant differences in the
      counts of extruded bacteria between groups (P > 0.05). The incidence and amount
      of apical bacterial extrusion were similar between the three systems. The
      customized apparatus was effective in collecting apically extruded bacteria.

PMID- 30113735
TI  - Classification and cyclic fatigue evaluation of new kinematics for endodontic
      instruments.
AB  - This study evaluated the effect of new motions of the motor TriAuto ZX2 on the
      cyclic fatigue of endodontic instruments. Vortex Blue 35.06 instruments were
      divided into four groups (n = 10) and tested for fatigue in a curved artificial
      canal (90 degrees  and 2 mm radius) using the following motions: continuous
      rotation (CR), Optimum Torque Reverse (OTR) set at 180 degrees  and the Optimum
      Glide Path (OGP), which was tested at 90 degrees  and 240 degrees . The time to
      fracture (TTF) and the lengths of the fractured fragments were recorded. The mean
      TTF was significantly different among the groups (anova, P < 0.05): OGP 90
      degrees  (213.39 +/- 27.45), OTR 180 degrees  (121.24 +/- 17.03), OGP 240 degrees
      (45.24 +/- 5.61) and CR (8.43 +/- 1.27). Weibull analysis confirmed the shortest
      life expectancy for CR and the longest survival for OGP at 90 degrees . The
      resistance to fatigue was affected by motions and pre-set angles. The proprietary
      movements that are currently available for endodontic instruments were classified
      according to their kinematics.

PMID- 30113736
TI  - Antimicrobial efficacy of clindamycin and triple antibiotic paste as root canal
      medicaments on tubular infection: An in vitro study.
AB  - This study compared the antibacterial effect of 2% clindamycin and 2% and 100%
      concentration of triple antibiotic paste (TAP) on an Enterococcus faecalis
      biofilm. Dentinal tubules of 100 root specimens were infected and randomly
      assigned to five groups. A total of 1000 mg mL-1 of TAP, 20 mg mL-1 of TAP and
      clindamycin, calcium hydroxide or methylcellulose (control) were placed in the
      root canal for 1 week. After treatment, dentine shavings were collected from 200
      and 400 MUm dentine depth and the number of colony-forming units (CFU) per mg was
      determined. Reduction in viable bacteria in first three groups was significantly
      better than calcium hydroxide and control groups. However, the antimicrobial
      effectiveness among these three groups was not significantly different from each
      other. There was no significant difference between data at 200 and 400 MUm in all
      groups except the Ca(OH)2 group. The antibiofilm effect of clindamycin was
      comparable with TAP, so it may be used instead of TAP.

PMID- 30113737
TI  - Macroscale analysis of mistletoe host ranges in the Andean-Patagonian forest.
AB  - The number of host species infected by a mistletoe (host range) is critical in
      that it influences prevalence, virulence and overall distribution of the
      parasite; however, macroecological analyses of this life history feature are
      lacking for many regions. The Andean-Patagonian forest, found along the southern
      Andes from 35  degrees S to Tierra del Fuego at 55  degrees S, contains 12
      mistletoe species in three families (Loranthaceae, Misodendraceae and
      Santalaceae). By tabulating herbarium records, the host ranges and geographical
      distributions of these mistletoes were explored. Our results show that these
      parasites occur on 43 plant species in 24 families but with varying degrees of
      specificity. All Misodendrum species and Desmaria mutabilis (Loranthaceae) are
      specialists that use Nothofagus as their primary hosts. Tristerix and Notanthera
      (Loranthaceae) and Antidaphne and Lepidoceras (Santalaceae) are generalists
      parasitizing more than six host species from several genera and families.
      Although many of the mistletoe species are sympatric, there is low overlap in
      host use. Our data show that in the southern South American bioregion, generalist
      mistletoes have smaller geographic ranges than specialists. This contrast with a
      previous hypothesis that predicted mistletoes with large geographic ranges would
      also have large host ranges, and conversely, less diverse regions would have more
      specialised mistletoes.

PMID- 30113738
TI  - Probabilistic classification of tumour habitats in soft tissue sarcoma.
AB  - The purpose of this work is to propose a method to characterize tumour
      heterogeneity on MRI, using probabilistic classification based on a reference
      tissue. The method uses maps of the apparent diffusion coefficient (ADC), T2
      relaxation, and a calculated map representing high-b-value diffusion-weighted MRI
      (denoted simDWI) to identify up to five habitats (i.e. sub-regions) of tumours.
      In this classification method, the parameter values (ADC, T2 , and simDWI) from
      each tumour voxel are compared against the corresponding parameter probability
      distributions in a reference tissue. The probability that a tumour voxel belongs
      to a specific habitat is the joint probability for all parameters. The
      classification can be visualized using a custom colour scheme. The proposed
      method was applied to data from seven patients with biopsy-confirmed soft tissue
      sarcoma, at three time-points over the course of pre-operative radiotherapy. Fast
      spin-echo images with two different echo times and diffusion MRI with three b
      values were obtained and used as inputs to the method. Imaging findings were
      compared with pathology reports from pre-radiotherapy biopsy and post-surgical
      resection. Regions of hypercellularity, high-T2 proteinaceous fluid, necrosis,
      collagenous stroma, and fibrosis were identified within soft tissue sarcoma. The
      classifications were qualitatively consistent with pathological observations. The
      percentage of necrosis on imaging correlated strongly with necrosis estimated
      from FDG-PET before radiotherapy (R2  = 0.97) and after radiotherapy (R2  =
      0.96). The probabilistic classification method identifies realistic habitats and
      reflects the complex microenvironment of tumours, as demonstrated in soft tissue
      sarcoma.

PMID- 30113740
TI  - Endodontic treatment of a hypertaurodontic mandibular left second molar in a
      patient with many taurodonts combined with multiple pulp stones.
AB  - Taurodontism is a rare embryologic anomaly of teeth, defined by an apical
      displacement of the furcation of roots and enlarged pulp chambers. Taurodontism
      has been classified as hypo-, meso- or hypertaurodontism according to the
      severity of the anomaly. The aim of this case report was to illustrate a clinical
      case with multiple bilateral taurodonts and to describe the endodontic management
      of the hypertaurodontic mandibular left second molar with a C-shaped canal and
      extensive dental pulp calcifications. A healthy 20-year-old male patient was
      referred for the endodontic treatment of his lower left second molar. Cone beam
      computed tomography revealed a C-shaped root canal configuration and several
      dental pulp calcifications in this tooth. The endodontic treatment was performed
      in two appointments under an operating dental microscope. A panoramic radiograph,
      made during the 18 months follow-up appointment, revealed nine other taurodontic
      molars, most of them associated with dental pulp calcifications.

PMID- 30113739
TI  - Calcifying epithelial odontogenic tumours: Collaborative study of 32 cases and
      review of literature.
AB  - OBJECTIVES: To analyse the occurrence of calcifying epithelial odontogenic
      tumours (CEOT) based on biopsy records from different Brazilian geographic
      regions and to contrast the data with a review of the literature. MATERIALS AND
      METHODS: A 2-step study was conducted. Step 1 consisted of a collaborative study
      of biopsies obtained from 1953 to 2017 at six Brazilian oral and maxillofacial
      pathology centres. Evaluation of 86,268 biopsy records was performed. Demographic
      and histopathological diagnosis data were assessed. In Step 2, a review of the
      literature of case reports and cases series of CEOT identified across five
      electronic databases was conducted. RESULTS: In the collaborative study, 32 cases
      of CEOT were evaluated. This figure represented 0.03% of the oral and
      maxillofacial lesions and 1.7% of all odontogenic tumours across the centres.
      Women in the fourth decade of life were more affected. CEOT occurred more in the
      mandible than in the maxilla (ratio 1.9:1). The review of the literature showed
      that Asian individuals were more affected by this neoplasm. CONCLUSIONS: Useful
      knowledge on the epidemiology, treatment and follow-up of CEOT has been provided.
      Demographic data and clinical features of the cases presented in this
      collaborative study were quite similar to those of studies reported worldwide.

PMID- 30113741
TI  - Undergraduate dentistry students' perception of difficulties regarding endodontic
      treatment.
AB  - The present study aimed to identify students' perceptions of endodontic treatment
      at a Brazilian university through a survey, which analysed student profiles and
      their difficulties in 2016. One hundred and two students who had experienced
      endodontic, laboratory or clinical procedures answered a survey based on their
      experiences, regarding their perceptions, experience and self-confidence levels.
      Results demonstrated that there was no significant difficulty among students
      regarding anaesthesia, rubber dam use, chamber access, working length
      determination, instrumentation, root filling and temporary restoration procedures
      during endodontic treatment. However, problems were observed regarding
      radiographic examination (mainly in separating root canals) and the choice of
      intracanal medication. The present study also raised a question regarding dental
      education: how can endodontic education be improved by addressing students'
      perceived difficulties? Evaluating the major student difficulties during root
      canal therapy can help the improvement of teaching strategies during preclinical
      and clinical teaching.

PMID- 30113742
TI  - Effectiveness of calcium and sodium hypochlorite in association with
      reciprocating instrumentation on decontamination of root canals infected with
      Enterococcus faecalis.
AB  - The aim of this study was to evaluate the antimicrobial activity of sodium and
      calcium hypochlorite utilising reciprocating instrumentation. Sixty root canals
      were inoculated with E. faecalis for 14 days. Samples were divided into six
      groups according to decontamination protocol: G1: no treatment, G2: distilled
      water, G3: 2.5% sodium hypochlorite, G4: 2.5% calcium hypochlorite, G5: 5.25%
      sodium hypochlorite and G6: 5.25% calcium hypochlorite. Instrumentation was
      performed with Wave One reciprocating system (Dentsply Sirona Endodontics, York,
      PA, USA) in groups G2 to G6. Colony-forming units (CFUs) counting was performed
      and the data were subjected to Anova and Tukey (alpha  =  0.05). Group 1 and 2
      showed the highest mean contamination, with a significant difference between them
      (P < 0.05). Groups 3, 4, 5 and 6 showed the lowest contamination means with no
      significant difference between them (P < 0.05). Sodium and calcium hypochlorite,
      in association with reciprocating instrumentation, can be an effective
      decontamination protocol in root canals infected with E. faecalis.

PMID- 30113743
TI  - Highly Flexible and Efficient All-Polymer Solar Cells with High-Viscosity
      Processing Polymer Additive toward Potential of Stretchable Devices.
AB  - Considering the potential applications of all-polymer solar cells (all-PSCs) as
      wearable power generators, there is an urgent need to develop photoactive layers
      that possess intrinsic mechanical endurance, while maintaining a high power
      conversion efficiency (PCE).Herein a strategy is demonstrated to simultaneously
      control the intercalation behavior and nanocrystallite size in the polymer
      polymer blend by using a newly developed, high-viscosity polymeric additive,
      poly(dimethylsiloxane-co-methyl phenethylsiloxane) (PDPS), into the TQ-F:N2200
      all-PSC matrix. A mechanically robust 10wt% PDPS blend film with a great
      toughness was obtained. Our results provide a feasible route for producing high
      performance ductile all-PSCs, which can potentially be used to realize
      stretchable all-PSCs as a linchpin of next-generation electronics.

PMID- 30113744
TI  - Cationic Complexes of Boron and Aluminum - An Early 21st Century Viewpoint.
AB  - Boron and aluminum share one main group, they are found in daily life
      commodities, and considered environmentally benign. Nevertheless, they markedly
      differ in their element properties (e.g. metal character, atomic radius). The use
      of Lewis acidic complexes of boron and aluminum for methods of bond activation
      and catalysis (e.g. hydrogenation of unsaturated substrates, polymerization of
      olefins and epoxides) is quickly expanding. The introduction of cationic charge
      may boost the metalloid-centered Lewis acidity and allows for its fine-tuning
      particularly with regard to preference for "hard" or "soft" Lewis bases (i.e.
      substrates). Especially, the isolation of low-coordinate cations (number of
      ligand atoms smaller than 4) demands for elaborate techniques of thermodynamic
      and kinetic stabilization (i.e. electronic saturation and steric shielding) by a
      ligand system. Furthermore, the properties of the solvent and the counteranion
      have to be considered with care. Herein, we revise selected examples for boron
      and aluminum cations.

PMID- 30113745
TI  - Discovery of Layered Indium Hydroxide via a Hydroperoxyl Anion Coordinated
      Precursor at Room Temperature.
AB  - All reported layered metal hydroxides have brucite-like metal-hydroxyl host
      layers, and the discovery of other types of layered metal hydroxides could
      significantly extend the layered metal hydroxide families, which is meaningful in
      both theory and applications. Here, through hydroperoxyl anion coordinated In3+
      cations as a precursor, a new layered indium hydroxide was synthesized, where
      only a three-dimensional cubic phase had existed before. The layer of the product
      exhibits an unusual structure where In(OH)6 octahedra share edges and vertexes
      with each other to form layers, which is completely different from the common
      edge-sharing brucite-like metal-hydroxyl layers. By investigating the formation
      mechanism, the new layered structure is found to be formed by changing the
      traditional crystallization path through the hydroperoxyl anion coordinated
      intermediates. Many other new phases could also be discovered by following the
      same intrinsic principle.

PMID- 30113746
TI  - Interactions between the perception of light and temperature.
AB  - Expanding the acceptable range of indoor temperatures allows to reduce building
      energy consumption and may be beneficial for health. Therefore, we explored
      whether light conditions can be used to influence thermal perception under
      various ambient temperatures. In two laboratory experiments, we tested the effect
      of the correlated color temperature of light (2700 K and 5800 K) and its
      intensity (5 and 1200 lux) on thermal perception. The light exposures were
      provided during cool, neutral, and warm thermal conditions. Cold-induced
      perceived shivering was higher for the 5800 K light exposure. All other
      parameters related to thermal perception did not significantly differ between the
      light exposures. Interestingly, the other way around, an increasing ambient
      temperature resulted in a warmer perception of the light color. In every light
      condition, it appeared that the perceived light intensity was closest to neutral
      under the thermoneutral condition. Between different light sessions, the change
      in visual comfort and the change in thermal comfort were positively related. The
      main conclusion therefore is that thermal discomfort can be partly compensated by
      lighting that results in a higher perceived visual comfort. Field studies are
      required to demonstrate whether lighting can enable new strategies to improve
      indoor environmental workplace satisfaction.

PMID- 30113747
TI  - Effect of sleep bruxism duration on perceived sleep quality in middle-aged
      subjects.
AB  - Sleep-related bruxism may directly impact sleep quality. This study aims to
      evaluate potential relationships between sleep bruxism events and related daytime
      symptoms. We investigated 22 patients (42.1 +/- 11.6 yr of age) with sleep
      bruxism in comparison with 12 good sleeper control subjects of similar age (41.0
      +/- 11.5 yr). Sleep bruxism was visually analyzed and categorized according to
      sleep stage, bruxism type (tonic/phasic) and duration. Clinical instruments
      comprised the Epworth Sleepiness, the Brugmann Fatigue Scale, and the Hospital
      Anxiety and Depression Rating Scale. Sleep quality was measured using the
      Pittsburgh Sleep Quality Index. Controls and patients with sleep bruxism
      presented similar sleep architecture. However, patients with sleep bruxism
      displayed significantly decreased sleep efficiency and higher sleep
      fragmentation. Perceived sleep quality was significantly worse in patients with
      sleep bruxism than in control subjects. Additionally, patients presented with
      significantly greater fatigue intensity and more affective symptoms than
      controls. The cumulative durations of sleep bruxism events (phasic, tonic, and
      combined) were significantly correlated with deterioration of sleep quality,
      whereas neither the event index per hour of sleep nor the count of event types
      (phasic/tonic) were related to sleep quality. Patients with sleep bruxism present
      with higher levels of daytime fatigue and sleepiness than control subjects who
      experience good sleep and may also exhibit impairments of sleep quality which are
      related to the duration of bruxism occurrence rather than to its frequency.

PMID- 30113749
TI  - Efficient Synthesis of Polysubstituted Pyrroles Based on [3+2] Cycloaddition
      Strategy Utilizing [1,2]-Phospha-Brook Rearrangement under Bronsted Base
      Catalysis.
AB  - An efficient method for the synthesis of polysubstituted pyrroles was established
      based on the [3+2] cycloaddition strategy utilizing the [1,2]-phospha-Brook
      rearrangement under Bronsted base catalysis. The less-explored approach of the
      [3+2] cycloaddition, that is, the reaction of a C3 subunit with imines, was
      successfully achieved by making use of newly designed C3 subunits containing the
      requisite umpolung. The two-step formal [3+2] cycloaddition involves the
      catalytic generation of an alpha-oxygenated propargyl anion through the [1,2]
      phospha-Brook rearrangement followed by gamma-addition to the imine under
      Bronsted base catalysis and the subsequent intramolecular cyclization mediated by
      Au catalyst or a halogenation reagent to afford polysubstituted pyrroles having a
      variety of substituents in a positional selective manner. The pyrroles thus
      synthesized were amenable to further transformations, such as palladium-catalyzed
      cross-coupling reactions. The operationally very simple method with readily
      available substrates provides new access to a diverse array of well-organized
      polysubstituted pyrroles.

PMID- 30113750
TI  - Adding vibration to high-intensity intervals increase time at high oxygen uptake
      in well-trained cyclists.
AB  - The importance of accumulated time >=90% of maximal oxygen consumption (VO2max )
      to improve performance in well-trained endurance athletes is well established.
      The present study compared the acute effects of adding vibrations (VIB; 40 Hz)
      with the work intervals during a high-intensity cycling session (HIT) with a
      traditional HIT session without vibration (TRAD) on time >=90% of VO2max , time
      >=90% of peak heart rate (HRpeak ), electromyography (EMG) activity, and mean
      power in well-trained cyclists (n = 10, VO2max =78.6 +/- 7.4 mL/min/kg). The
      order of VIB and TRAD was randomized and consisted of 6 * 5-minutes work
      intervals performed with the highest possible mean power across the work
      intervals (2.5-minutes standardized relief periods). VIB was superior to TRAD on
      time >=90% of VO2max , (10.99 +/- 7.00 vs 6.95 +/- 5.28 minutes, respectively),
      time >=90% of HRpeak (24.61 +/- 2.38 vs 19.97 +/- 4.12 minutes, respectively),
      and averaged EMG activity in m. Vastus Lateralis during the work intervals (all P
      < 0.05). The EMG/power output ratio across all work intervals was higher in VIB
      than TRAD (P < 0.05). Mean values across work intervals showed no difference
      between VIB and TRAD in mean power, rate of perceived exertion, or blood lactate
      concentration. Thus, the present study indicated that adding vibration to the
      work intervals during a HIT session can acutely increase the physiological
      responses of the cardiovascular system and increase time >=90% VO2max and should
      therefore be considered in order to optimize the exercise stimulus of well
      trained cyclists.

PMID- 30113748
TI  - Total Synthesis, Stereochemical Assignment, and Divergent Enantioselective
      Enzymatic Recognition of Larreatricin.
AB  - A concise and efficient total synthesis of the lignan natural product
      larreatricin as well as an unambiguous assignment of configuration of its
      enantiomers are reported, resolving a long-held controversy. Enzyme kinetic
      studies revealed that different polyphenol oxidases show high and remarkably
      divergent enantioselective recognition of this secondary metabolite.

PMID- 30113751
TI  - External invasive resorption: Case report of a rapidly progressive process in an
      impacted maxillary canine during orthodontic treatment.
AB  - External invasive resorption (EIR) is a type of external resorption that can
      involve the coronal, middle and apical parts of the root in its advanced stages
      and results in progressive loss of tooth structure. Common potential predisposing
      factors for EIR are orthodontic treatment and trauma. The EIR progression rate
      has not been described previously. This case report describes rapidly progressive
      EIR in an impacted maxillary canine after surgical exposure and application of
      directional orthodontic traction over 8 months. The article discusses the
      etiologies of EIR, the possible reasons for EIR and its rapid progression in the
      presented case and proposes a new theory of the connection between EIR and tooth
      impaction.

PMID- 30113752
TI  - Real-time curing characteristics of experimental resin composites containing
      amorphous calcium phosphate.
AB  - The real-time polymerization of light-curable experimental resin composites
      filled with amorphous calcium phosphate (ACP) was monitored. Experimental
      composites were based on a 2,2-bis[4-(2-ethoxy-3-methacryloyloxy
      propoxy)phenyl]propane (Bis-EMA)/triethyleneglycol dimethacrylate (TEGDMA)/2
      hydroxyethyl methacrylate (HEMA) resin photoactivated by a
      camphorquinone/tertiary amine system. Four ACP composites were prepared,
      containing 40 wt% ACP and 0/10 wt% reinforcing fillers (barium glass and silica).
      Additionally, two control composites were prepared which contained only
      reinforcing fillers (40-50 wt%). The degree of conversion (DC) was monitored in
      real time using a Fourier-transform infrared (FTIR) spectrometer with an
      attenuated total reflectance accessory. During the light curing (1,219 mW cm-2 )
      for either 20 or 40 s, infrared spectra were collected from the bottom of 2-mm
      thick composite specimens at the rate of two spectra per second over 5 min. When
      cured for 40 s, the ACP composites attained a high DC (89.1%-92.4%), while the DC
      of control composites was significantly lower (53.5%-68.4%). All materials showed
      a lower DC for the shorter curing time (20 s) and various extents of 5-min
      postcure polymerization: 12.9%-21.5% for the ACP composites and 2.7%-5.2% for the
      control composites. The control composites reached the maximum reaction rate much
      earlier (4.1-4.3 s) and at lower DC (9.9%-10.4%) than did the ACP composites
      (17.4-22.0 s and 43.5%-49.3%, respectively).

PMID- 30113753
TI  - Modelling white matter with spherical deconvolution: How and why?
AB  - Since the realization that diffusion MRI can probe the microstructural
      organization and orientation of biological tissue in vivo and non-invasively, a
      multitude of diffusion imaging methods have been developed and applied to study
      the living human brain. Diffusion tensor imaging was the first model to be widely
      adopted in clinical and neuroscience research, but it was also clear from the
      beginning that it suffered from limitations when mapping complex configurations,
      such as crossing fibres. In this review, we highlight the main steps that have
      led the field of diffusion imaging to move from the tensor model to the adoption
      of diffusion and fibre orientation density functions as a more effective way to
      describe the complexity of white matter organization within each brain voxel.
      Among several techniques, spherical deconvolution has emerged today as one of the
      main approaches to model multiple fibre orientations and for tractography
      applications. Here we illustrate the main concepts and the reasoning behind this
      technique, as well as the latest developments in the field. The final part of
      this review provides practical guidelines and recommendations on how to set up
      processing and acquisition protocols suitable for spherical deconvolution.

PMID- 30113754
TI  - Prostatic capsular incision during radical prostatectomy has important
      oncological implications. A systematic review and meta-analysis.
AB  - INTRODUCTION: Capsular Incision (CapI) is an iatrogenic breach of the prostatic
      capsule during radical prostatectomy that can cause positive surgical margins
      (PSM) in organ-confined (pT2) prostate cancer (PCa), or the retention of benign
      prostatic tissue. We systematically interrogated the literature in order to
      clarify the definition of CapI, and the implications of this event for rates of
      PSM and biochemical recurrence (BCR). METHODS: A literature search was conducted
      according to PRISMA criteria using the search terms 'CapI' AND 'prostatectomy'
      and variations of each. 18 studies were eligible for inclusion. RESULTS: A total
      of 51,057 radical prostatectomy specimens were included. The incidence of CapI
      ranged from 1.3-54.3%. CapI definitions varied, and included a breach of the
      prostatic capsule "exposing both benign or malignant PCa cells", "malignant
      tissue only", or "benign tissue only". The incidence of PSM due to CapI ranged
      from 2.8 - 71.7%. Our meta-analysis results found that when CapI was defined as
      "exposing malignant tissue only in organ-confined prostate cancer" there was an
      increased risk of BCR compared to patients with pT2 disease and no CapI (RR 3.53,
      95%CI 2.82-4.41; p < 0.00001). CONCLUSIONS: The absolute impact of CapI on
      oncological outcomes is currently unclear due to inconsistent definitions.
      However, the data implies an association between CapI and PSM and BCR. Reporting
      of possible areas of CapI on the operation note, or marking areas of concern on
      the specimen, are critical to assist CapI recognition by the pathologist. This
      article is protected by copyright. All rights reserved.

PMID- 30113755
TI  - Four-year outcomes from a multiparametric magnetic resonance imaging (MRI)-based
      active surveillance programme: PSA dynamics and serial MRI scans allow omission
      of protocol biopsies.
AB  - OBJECTIVES: To report outcomes from a multiparametric (mp) magnetic resonance
      imaging (MRI)-based active surveillance programme that did not include performing
      protocol biopsies after the first confirmatory biopsy. PATIENTS AND METHODS: All
      patients diagnosed with Gleason 3 + 3 prostate cancer because of a raised PSA
      level who underwent mpMRI after diagnosis were included. Patients were recorded
      in a prospective clinical database and followed up with PSA monitoring and repeat
      MRI. In patients who remained on active surveillance after the first MRI (with or
      without confirmatory biopsy), we investigated PSA dynamics for association with
      subsequent progression. Comparison between first and second MRI scans was
      undertaken. Outcomes assessed were: progression to radical therapy at first
      MRI/confirmatory biopsy and progression to radical therapy in those who remained
      on active surveillance after first MRI. RESULTS: A total of 211 patients were
      included, with a median of 4.2 years of follow-up. The rate of progression to
      radical therapy was significantly greater at all stages among patients with
      visible lesions than in those with initially negative MRI (47/125 (37.6%) vs
      11/86 (12.8%); odds ratio 4.1 (95% CI 2.0-8.5), P < 0.001). Only 1/56 patients
      (1.8%) with negative initial MRI scans who underwent a confirmatory systematic
      biopsy had upgrading to Gleason 3 + 4 disease. PSA velocity was significantly
      associated with subsequent progression in patients with negative initial MRI
      (area under the curve 0.85 [95% CI 0.75-0.94]; P <0.001). Patients with high-risk
      visible lesions on first MRI who remained on active surveillance had a high risk
      of subsequent progression 19/76 (25.0%) vs 9/84 (10.7%) for patients with no
      visible lesions, despite reassuring targeted and systematic confirmatory biopsies
      and regardless of PSA dynamics. CONCLUSION: Men with low-risk Gleason 3 + 3
      prostate cancer on active surveillance can forgo protocol biopsies in favour of
      MRI and PSA monitoring with selective re-biopsy.

PMID- 30113756
TI  - An analysis of the frequency of Y-chromosome microdeletions and the determination
      of a threshold sperm concentration for genetic testing in infertile men.
AB  - OBJECTIVE: To describe the prevalence of Y-chromosome microdeletions in a multi
      ethnic urban population in London, UK. To also determine predictive factors and a
      clinical threshold for genetic testing in men with Y chromosome microdeletions.
      PATIENTS AND METHODS: A retrospective cohort study of 1473 men that were referred
      to a tertiary Andrology centre with male factor infertility between July 2004 and
      December 2016. All had a genetic evaluation, hormonal profile and 2 abnormal
      semen analyses. Those with abnormal examination findings also had targeted
      imaging performed. RESULTS: The prevalence of microdeletions was 4% (n = 58) in
      this study. These microdeletions were partitioned into the following regions:
      Azoospermia factors (AZF); AZFc (75%), AZFb+c (13.8%), AZFb (6.9%), AZFa (1.7%),
      and partial AZFa (1.7%). A high follicle-stimulating hormone level (P < 0.001)
      and a low sperm concentration (P < 0.05) were both found to be significant
      predictors for the identification of a microdeletion. Testosterone level,
      luteinising hormone level and testicular volume did not predict the presence of a
      microdeletion. None of the men with an AZF microdeletion had a sperm
      concentration of >0.5 million/mL. Lowering the sperm concentration threshold to
      this level retained the high sensitivity (100%) and increased the specificity
      (31%). This would produce significant cost savings when compared to the European
      Academy of Andrology/European Molecular Genetics Quality Network and European
      Association of Urology guidelines. The surgical sperm retrieval (SSR) rate after
      microdissection testicular sperm extraction was 33.2% in men with AZFc
      microdeletion. CONCLUSIONS: The prevalence of Y-chromosome microdeletions in
      infertile men appears to vary between populations and countries. A low sperm
      concentration was a predictive factor (P < 0.05) for identifying microdeletions
      in infertile males. A threshold for genetic testing of 0.5 million/mL would
      increase the specificity and lower the relative cost without adversely affecting
      the sensitivity. The rate of SSR was lower than that previously described in the
      literature.

PMID- 30113757
TI  - Bladder emptying method is the primary determinant of urinary tract infections in
      patients with spinal cord injury: results from a prospective rehabilitation
      cohort study.
AB  - OBJECTIVE: To understand the occurrence of and risk factors for urinary tract
      infections (UTIs) in patients with spinal cord injury (SCI) undergoing
      specialized SCI rehabilitation in Switzerland. PATIENTS AND METHODS: This study
      used data collected from 369 patients, who participated in a nationwide
      rehabilitation cohort for SCI in Switzerland between 2013 and 2017. Information
      on UTIs as well as their potential determinants, including demographics, lesion
      characteristics, and time-updated data on functional independence and bladder
      management, was used. Multivariable regression methods were applied to perform a
      time-updated evaluation of determinants of UTI risk. RESULTS: The crude incidence
      rate (IR) of UTIs was 0.55 UTIs per 100 person-days (95% confidence interval [CI]
      0.49-0.62), the cumulative IR was 43%, and the median length of stay was 122
      days. The bladder emptying method at discharge was largely determined by 28 days
      after admission. Among those using indwelling or assisted intermittent
      catheterization (IC), the likelihood of self-IC at discharge was positively
      related to the level of self-care independence, negatively related to age at
      injury, and lower in women than men. Catheter users consistently had higher
      adjusted IRs for UTI than spontaneous voiders. The IR ratios were: indwelling
      catheter: 5.97 (95% CI 2.63-13.57); assisted IC: 6.05 (95% CI 2.63-13.94); self
      IC: 5.16 (95% CI 2.31-11.52); test for differences across catheter groups: P =
      0.82. Lesion severity and previous UTI had additional but smaller effect sizes.
      CONCLUSIONS: Bladder emptying method was identified as the main risk factor for
      UTI in patients with SCI. As spontaneous voiders had the lowest UTI rate, further
      research is warranted to reduce voiding dysfunction, for instance using
      neuromodulation procedures.

PMID- 30113758
TI  - Current management of radiation cystitis: a review and practical guide to
      clinical management.
AB  - INTRODUCTION: Haemorrhage is a frequent complication of radiation cystitis
      leading to emergency presentations in patients with prior pelvic radiation
      therapy. Standard initial patient management strategies involve resuscitation,
      bladder washout with clot evacuation and continuous bladder irrigation. Beyond
      this, definitive surgical treatment is associated with significant morbidity and
      mortality. Alternative less invasive management options for non-emergent
      haemorrhagic cystitis include systemic medical therapies, hyperbaric oxygen
      (HBO), intravesical therapies and laser ablation. However, evidence to support
      and compare treatment for haemorrhagic radiation cystitis is limited. METHODS:
      Herein, a literature search pertaining to the current management of haemorrhagic
      cystitis was conducted. RESULTS: In total, 23 studies were included in this
      review with 2 studies reviewing systemic therapy, 7 studies evaluating HBO
      therapy, 10 studies investigating a variety of intravesical therapies and the
      remaining 4 were relating to ablative therapies. Across these studies, the
      patient groups were heterogenous with small numbers and variable follow up
      periods. CONCLUSION: With evaluation of existing literature, this narrative
      review also provides a stepwise clinical algorithm to aid the urologist in
      treating patients presenting with complications associated with radiation
      cystitis.

PMID- 30113759
TI  - Development of field cancerization in the clinically normal oral mucosa of shisha
      smokers.
AB  - OBJECTIVES: This study aimed to investigate the changes that occur in the oral
      mucosa of shisha smokers and compare them to cigarette smokers, nonsmokers and
      smokers of both shisha and cigarettes and to detect whether these changes could
      be detected biochemically in saliva. METHODS: Four groups of subjects were
      included in our study (16 in each group); cigarette smokers, shisha smokers,
      nonsmokers and smokers of both. A salivary sample and a mucosal biopsy were
      obtained from each subject. Salivary detection of CYFRA 21-1 was performed on
      each salivary sample. The mucosal biopsy was examined by routine H&E techniques.
      Furthermore, immunohistochemical expression of p53 was studied in all cases.
      RESULTS: A statistically significant difference in p53 expression was present
      between nonsmokers and the three smoker groups. However, no statistically
      significant variation was present between the 3 smoker groups. Furthermore, no
      statistically significant changes were found in the CYFRA 21-1 levels among the
      four groups. CONCLUSION: Shisha smoking has the same damaging effect on the oral
      mucosa as cigarette smoking. Furthermore, no correlation was detected between the
      histological findings and the salivary biomarker used (CYFRA 21-1).

PMID- 30113760
TI  - Multipurpose Antifouling Coating of Solid Surfaces with the Marine-Derived
      Polymer Fucoidan.
AB  - The control of biofouling, which is the unwanted adsorption of biomolecules and
      organisms on solid surfaces, is a prerequisite for wider applicability of the
      functional materials that are currently being used in biomedical industries. One
      of the frequently used methods for controlling biofouling is the use of surface
      coatings with antifouling materials. Herein, fucoidan, which is a marine-derived
      polysaccharide, is reported as a new type of antifouling material that is safe
      and broadly applicable. Fucoidan is conjugated with catechols, which are known to
      act as adhesives for grafting functional molecules onto solid substrates.
      Fucoidan catechol (FD-C) is subsequently utilized for robust fucoidan coatings of
      solid substrates, and the FD-C-coated surfaces show excellent antifouling
      capability for fouling organisms, including platelets and bacteria. The FD-C
      coating is also confirmed to be nonirritating upon skin contact, demonstrating
      its potential use in public places for inhibiting contagions.

PMID- 30113761
TI  - From validity to clinical utility: the influence of circulating tumor DNA on
      melanoma patient management in a real-world setting.
AB  - Melanoma currently lacks a reliable blood-based biomarker of disease activity,
      although circulating tumor DNA (ctDNA) may fill this role. We investigated the
      clinical utility (i.e., impact on clinical outcomes and interpretation of
      radiographic data) of measuring ctDNA in patients with metastatic or high-risk
      resected melanoma. Patients were prospectively accrued into >= 1 of three
      cohorts, as follows. Cohort A: patients with radiographically measurable
      metastatic melanoma who underwent comparison of ctDNA measured by a BEAMing
      digital PCR assay to tissue mutational status and total tumor burden; when
      appropriate, determinations about initiation of targeted therapy were based on
      ctDNA data. Cohorts B and C: patients with BRAF- or NRAS-mutant melanoma who had
      either undergone surgical resection of high-risk disease (cohort B) or were
      receiving or had received medical therapy for advanced disease (cohort C).
      Patients were followed longitudinally with serial ctDNA measurements with
      contemporaneous radiographic imaging to ascertain times to detection of disease
      activity and progressive disease, respectively. The sensitivity and specificity
      of the ctDNA assay were 86.8% and 100%, respectively. Higher tumor burden and
      visceral metastases were found to be associated with detectable ctDNA. In two
      patients in cohort A, ctDNA test results revealed a targetable mutation where
      tumor testing had not; both patients experienced a partial response to targeted
      therapy. In four of 30 patients with advanced melanoma, ctDNA assessments
      indicated evidence of melanoma activity that predicted radiographic evidence of
      disease progression by 8, 14, 25, and 38 weeks, respectively. CtDNA was
      detectable in three of these four patients coincident with radiographic
      evaluations that alone were interpreted as showing no evidence of neoplastic
      disease. Our findings provide evidence for the clinical utility of integrating
      ctDNA data in managing patients with melanoma in a real-world setting.

PMID- 30113762
TI  - Explorative study on quality of life in relation to salivary secretion rate in
      head and neck cancer patients treated with radiotherapy up to 2 years post
      treatment.
AB  - OBJECTIVE: The aim of this study was to analyse quality of life (QoL)
      pretreatment and up to 24 months post radiation therapy (RT) in patients with
      head and neck (H&N) cancer. METHODS: Twenty-nine patients (19 men and 10 women)
      with a mean age of 59 +/- 8 years were included. The stimulated salivary
      secretion was measured and the patients completed the European Organisation for
      Research and Treatment of Cancer Quality of Life questionnaires (EORTC QLQ-C30
      and H&N35) and the Hospital Anxiety and Depression scale (HADS) pretreatment and
      at 6, 12 and 24 months post RT. RESULTS: At all time-points after RT (6, 12, and
      24 months), patients with hyposalivation (stimulated secretion rate <=0.7 mL/min)
      reported clinically significant differences (> 10 points) regarding insomnia,
      swallowing, social eating, dry mouth, and sticky saliva. Statistically
      significant differences were found for emotional functioning and insomnia at 12
      months (P < 0.05 for both) and for sticky saliva at both 12 and 24 months (P <
      0.05 and P < 0.01). The number of clinically significant differences increased
      from 10 at both 6 and 12 months post-RT to 14 functioning/symptom scales and
      single items at the 24 months follow-up. At 24 months post RT, 21% of patients
      with hyposalivation had HADS scores suggesting anxiety problems compared to 7%
      for those with stimulated salivary secretion rates >0.7 mL/min. CONCLUSION:
      Patients with hyposalivation showed deterioration in health related quality of
      life (QoL) at 24 months compared with 12 months post RT. Most pronounced were
      problems with insomnia, swallowing, social eating, dry mouth, and sticky saliva.

PMID- 30113763
TI  - Hyperbaric oxygen treatment for the management of radiation-induced xerostomia.
AB  - INTRODUCTION: Hyperbaric oxygen therapy (HBOT) is widely used for the treatment
      of the late effects of radiation therapy. We report a prospective observational
      cohort study of 51 patients designed to examine the effectiveness of hyperbaric
      oxygen treatment (HBOT) for xerostomia following radiotherapy. METHODS: Objective
      (saliva volume) and subjective (quality of life scoring and visual analogue scale
      (VAS) of discomfort) measurements associated with xerostomia were compared prior
      to commencement of HBOT, after 30 sessions (over 6 weeks) of HBOT at 243 kPa for
      90 minutes daily for five days per week and at 6-week review (12 weeks from
      commencement). RESULTS: One hundred and one courses of treatment in 99 patients
      were examined. For 53 (53%) courses in 51 patients, data were recorded before and
      after HBOT and so could be included in the analysis. Thirty-four (34%) of these
      patients had complete data for all three time points. The unit of study was per
      treatment course, not per person. There were no major complications to HBOT.
      There was a statistically significant difference in saliva volume following HBOT
      (P = 0.016). The mean saliva volume increase was 0.9 mL over a 5-min collection
      period (95% CI 0.2-1.5). There was also a statistically significant improvement
      in discomfort after HBOT (P < 0.001) and QOL (P < 0.001). The mean visual
      analogue scale for discomfort (VAS on a 0-10 scale) score decreased by 1.4 units
      (95% CI 0.7-2.1), whilst the mean QOL score was 10 points lower after treatment
      (95% CI 5.9-14.4). CONCLUSION: Hyperbaric oxygen therapy may be a safe and
      effective treatment for symptoms of xerostomia after radiation therapy and should
      be considered when available.

PMID- 30113765
TI  - Marked acanthocytosis in the setting of Klippel-Trenaunay syndrome: A case
      report.

PMID- 30113764
TI  - Easy discrimination of hematogones from lymphoblasts in B-cell progenitor acute
      lymphoblastic leukemia patients using CD81/CD58 expression ratio.
AB  - INTRODUCTION: The discrimination of leukemia lymphoblasts (LB) in diagnosis and
      follow-up of B-cell progenitor acute lymphoblastic leukemia (BCP-ALL) by
      multiparameter flow cytometry (MFC) may be difficult due to the presence of
      hematogones (HG). The aim of this study was to compare lymphoblasts of BCP-ALL
      and HG for the expression of the most discriminating antigens. METHODS: A total
      of 82 bone marrow samples (39 BCP-ALL and 43 patients with HG) were analyzed
      using MFC. Mean fluorescence intensity (MFI) was measured for ten markers
      commonly used in hematology laboratories: CD45, CD19, CD10, CD34, CD38, CD20,
      CD22, CD58, CD81, and CD123. Statistical comparison of the MFI between LB and HG
      was performed. The presence on LB of aberrant expression of myeloid and/or T-cell
      markers was also investigated. RESULTS: Qualitative pattern expression of
      antigens showed overexpression on LB of CD58, CD22, CD34, CD10 and
      underexpression of CD81, CD45, CD38 when compared to HG. Expression of CD123 was
      positive in 34% of BCP-ALL LB and always absent on HG. Aberrant antigen
      expression (myeloid and/or T-cell marker) including CD123 was observed in 58% of
      BCP-ALL patients. The use of a MFI antigen ratio of the most discriminating
      markers (CD81/CD58) (analysis of variance, P < 0.005) increased the distinction
      of LB versus HG with a high specificity and sensitivity as demonstrated by the
      use of ROC curve analysis (AUC of CD81/CD58: 0.995). CONCLUSION: We demonstrate
      in this study that routine use of the MFI antigen ratio (CD81/CD58) in addition
      to the MFC evaluation using WHO classical criteria appears to be an efficient
      approach to discriminate LB from HG.

PMID- 30113766
TI  - Advanced musculoskeletal physiotherapy: Barriers and enablers to multi-site
      implementation.
AB  - OBJECTIVES: Advanced musculoskeletal physiotherapy (AMP) services are a safe,
      effective model of care, but without broad-scale healthcare implementation to
      date. The aim of the present study was to identify the barriers and enablers to
      implementation of 12 AMP services from the perspective of clinical staff.
      METHODS: In a qualitative study, 12 participants (physiotherapists), from 12
      different healthcare networks (seven metropolitan, three regional, two rural),
      were included. Their departments implemented AMP services (orthopaedic
      postoperative joint replacement review, n = 10; general orthopaedic, n = 1;
      emergency, n = 1; and neurosurgery n = 1) over a 12-month period. Participants
      completed a structured survey specifically designed for the study. Thematic
      analysis was used, with themes mapped to the validated Theoretical Domains
      Framework. RESULTS: Nine major themes emerged from the data regarding barriers
      and enablers to the implementation of the AMP services from the perspective of
      clinical staff. These were: demand/capacity; model of care; the organization;
      stakeholders; communication; planning and processes; evaluation; workforce; and
      learning and assessment framework. Important enablers included engagement and buy
      in from key stakeholders and medical staff, and well-established AMP learning
      frameworks for training and operational frameworks. Barriers included competitive
      funding environment, and issues that hindered effective communication. The
      knowledge, skills, availability, motivation and experience of the advanced
      musculoskeletal physiotherapists had a large impact on the implementation.
      CONCLUSIONS: The study identified a number of factors that should be considered
      for successful implementation of AMP services across healthcare services or wider
      healthcare networks.

PMID- 30113767
TI  - Enhancer activities of amphioxus Brachyury genes in embryos of the ascidian,
      Ciona intestinalis.
AB  - The notochord and somites are distinctive chordate structures. The T-box
      transcription factor gene, Brachyury, is expressed in notochord and plays a
      pivotal role in its formation. In the cephalochordate, Branchiostoma floridae,
      Brachyury is duplicated into BfBra1 and BfBra2, which are expressed in the somite
      formation region as well. In a series of experiments to elucidate the regulatory
      machinery of chordate Brachyury expression, we carried out a lacZ reporter assay
      of BfBra in embryos of the urochordate, Ciona intestinalis. Vista analyses
      suggest the presence of conserved non-coding sequences, not only in the 5'
      upstream, but also in the 3'-downstream and in introns of BfBra. We found that:
      (1) 5'-upstream sequences of both BfBra1 and BfBra2 promote lacZ expression in
      muscle cells, (2) 3'-downstream sequences have enhancer activity that promotes
      lacZ expression in notochord cells, and (3) introns of BfBra2 and BfBra1 exhibit
      lacZ expression preferentially in muscle and notochord cells. These results
      suggest shared cephalochordate Brachyury enhancer machinery that also works in
      urochordates. We discuss the results in relation to evolutionary modification of
      Brachyury expression in formation of chordate-specific organs characteristic of
      each lineage.

PMID- 30113768
TI  - Prognostic evaluation of perinephric fat, renal sinus fat, and renal vein
      invasion for patients with pathological stage T3a clear-cell renal cell
      carcinoma.
AB  - OBJECTIVE: To investigate the prognostic significance of various patterns of
      extrarenal extension that comprise pathological stage T3a clear-cell renal cell
      carcinoma (ccRCC) amongst patients undergoing nephrectomy for non-metastatic
      disease. PATIENTS AND METHODS: A retrospective review of 563 patients who
      underwent radical nephrectomy for pathologically confirmed T3aN0/NxM0 ccRCC
      between 1970 and 2011 was performed. All pathological slides were re-reviewed by
      one urological pathologist. Associations of patterns of extrarenal extension
      (perinephric fat [PF], renal sinus fat [SF], and renal vein [RV], in isolation or
      in any combination) with disease progression, cancer-specific mortality (CSM),
      and all-cause mortality were evaluated on multivariable analyses. RESULTS:
      Overall, PF invasion, renal SF invasion, and RV tumour thrombus were present in
      144 (26%), 51 (9%), and 163 (29%) patients, respectively, with multiple patterns
      of extrarenal extension identified in 205 (36%) patients. There were no
      significant differences in survival outcomes for isolated involvement of PF,
      renal SF, or RV. However, patients with multiple patterns of extrarenal extension
      were at significantly increased risk of disease progression (hazard ratio [HR]
      1.31, 95% confidence interval [CI] 1.04-1.65; P = 0.020), CSM (HR 1.64, 95% CI
      1.27-2.12; P < 0.001), and all-cause mortality (HR 1.32, 95% CI 1.08-1.61; P =
      0.008). CONCLUSIONS: The presence of multiple patterns of extrarenal extension is
      associated with a higher risk of disease progression and cancer-related death
      after radical nephrectomy compared to isolated involvement of the PF, renal SF,
      or RV, which carry similar prognostic weight. If validated, these findings may
      help refine risk stratification of non-metastatic T3a RCC by distinguishing
      patients with multiple vs one pattern of extrarenal extension.

PMID- 30113769
TI  - An approach for controlling the timing and order of engineered mutations in mice.
AB  - Significant advances in our understanding of normal development and disease have
      been facilitated by engineered mice in which genes can be altered in a spatially,
      temporally, or cell type restricted manner using site specific recombinase
      systems like Cre-loxP or Flp-frt. In many circumstances it is important to
      understand how interactions between multiple genes influence a given phenotype.
      Robust approaches for precisely controlling multiple genetic alterations
      independently are limited, however, thus the impact of mutation order and timing
      on phenotype is generally unknown. Here we describe and validate a novel
      Gt(ROSA)26Sor targeted transgene allowing precise control over the order and
      timing of multiple genetic mutations in the mouse. The transgene expresses an
      optimized, Flp-estrogen receptor fusion protein (Flpo-ERT2) under the control of
      a loxP-stop-loxP cassette. In this system, genes modified by loxP sites are
      altered first upon expression of Cre. Cre also eliminates the loxP-stop-loxP
      cassette, permitting widespread expression of Flpo-ERT2. Because of the estrogen
      receptor fusion, Flp activity remains inert until administration of tamoxifen,
      allowing genes modified by frt sites to be modified subsequently with
      controllable timing. This mouse transgene will be useful in a wide variety of
      applications where independent control of different mutations in the mouse is
      desirable.

PMID- 30113771
TI  - Comparison of rest-break interventions during a mentally demanding task.
AB  - Research is scarce on ways to enhance the effect of rest breaks during mentally
      demanding tasks. The present study investigated the effectiveness of two rest
      break interventions on well-being during an academic lecture. Sixty-six students
      (53 females, mean age 22.5 years) enrolled in two different university classes of
      4-hr duration participated in the study. Two measures of well-being (fatigue and
      vigor) were assessed immediately before, after, and 20 minutes after the break. A
      control condition without a break as well as an unstructured break was compared
      with breaks either encompassing physical activity or a relaxation exercise.
      Compared with the nonbreak condition, the unstructured rest break led to an
      increase in vigor, the exercise break as well as the relaxation break both to an
      increase in vigor and a decrease in fatigue at 20-min post break. Compared with
      the unstructured break, exercise led to an (additional) increase in vigor and
      relaxation to an (additional) decrease in fatigue at 20-min post break. Thus, the
      effects of rest breaks during mentally demanding tasks can be enhanced by
      engaging in physical activity or relaxation exercises, with effects lasting at
      least as long as 20 min into the continuation of the task.

PMID- 30113770
TI  - GmBTB/POZ, a novel BTB/POZ domain-containing nuclear protein, positively
      regulates the response of soybean to Phytophthora sojae infection.
AB  - Phytophthora sojae is a destructive pathogen of soybean [Glycine max (L.) Merr.]
      which causes stem and root rot on soybean plants worldwide. However, the
      pathogenesis and molecular mechanism of plant defence responses against P. sojae
      are largely unclear. Herein, we document the underlying mechanisms and function
      of a novel BTB/POZ protein, GmBTB/POZ, which contains a BTB/POZ domain found in
      certain animal transcriptional regulators, in host soybean plants in response to
      P. sojae. It is located in the cell nucleus and is transcriptionally up-regulated
      by P. sojae. Overexpression of GmBTB/POZ in soybean resulted in enhanced
      resistance to P. sojae. The activities and expression levels of enzymatic
      superoxide dismutase (SOD) and peroxidase (POD) antioxidants were significantly
      higher in GmBTB/POZ-overexpressing (GmBTB/POZ-OE) transgenic soybean plants than
      in wild-type (WT) plants treated with sterile water or infected with P. sojae.
      The transcript levels of defence-associated genes were also higher in
      overexpressing plants than in WT on infection. Moreover, salicylic acid (SA)
      levels and the transcript levels of SA biosynthesis-related genes were markedly
      higher in GmBTB/POZ-OE transgenic soybean than in WT, but there were almost no
      differences in jasmonic acid (JA) levels or JA biosynthesis-related gene
      expression between GmBTB/POZ-OE and WT soybean lines. Furthermore, exogenous SA
      application induced the expression of GmBTB/POZ and inhibited the increase in P.
      sojae biomass in both WT and GmBTB/POZ-OE transgenic soybean plants. Taken
      together, these results suggest that GmBTB/POZ plays a positive role in P. sojae
      resistance and the defence response in soybean via a process that might be
      dependent on SA.

PMID- 30113772
TI  - Phenotypic severity scoring system and categorisation for prune belly syndrome:
      application to a pilot cohort of 50 living patients.
AB  - OBJECTIVE: To design a novel system of scoring prune belly syndrome (PBS)
      phenotypic severity at any presenting age and apply it to a large pilot cohort.
      PATIENTS AND METHODS: From 2000 to 2017, patients with PBS were recruited to our
      prospective PBS study and medical records were cross-sectionally analysed,
      generating individualised RUBACE scores. We designed the pragmatic RUBACE-scoring
      system based on six sub-scores (R: renal, U: ureter, B: bladder/outlet, A:
      abdominal wall, C: cryptorchidism, E: extra-genitourinary, generating the acronym
      RUBACE), yielding a potential summed score of 0-31. The 'E' score was used to
      segregate syndromic PBS and PBS-plus variants. The cohort was scored per classic
      Woodard criteria and RUBACE scores compared to Woodard category. RESULTS: In all,
      48 males and two females had a mean (range) RUBACE score of 13.8 (8-25) at a mean
      age of 7.3 years. Segregated by phenotypic categories, there were 39 isolated PBS
      (76%), six syndromic PBS (12%) and five PBS-plus (10%) cases. The mean RUBACE
      scores for Woodard categories 1, 2, and 3 were 20.5 (eight patients), 13.8 (25),
      and 10.6 (17), respectively (P < 0.001). CONCLUSIONS: RUBACE is a practical,
      organ/system level, phenotyping tool designed to grade PBS severity and
      categorise patients into isolated PBS, syndromic PBS, and PBS-plus groups. This
      standardised system will facilitate genotype-phenotype correlations and future
      prospective multicentre studies assessing medical and surgical treatment
      outcomes.

PMID- 30113773
TI  - Biallelic deletions of the Waardenburg II syndrome gene, SOX10, cause a
      recognizable arthrogryposis syndrome.
AB  - Random mating in the general population tends to limit the occurrence of
      homozygous and compound heterozygous forms of dominant hereditary disorders.
      Certain phenotypes, the most recognized being skeletal dysplasias associated with
      short stature, lead to cultural interaction and assortative mating. To this well
      known example, may be added deafness which brings together individuals with a
      variety of deafness genotypes, some being dominant. Waardenburg syndrome is one
      such autosomal dominant disorder in which affected individuals may interact
      culturally because of deafness. Biallelic genetic alterations for two Waardenburg
      genes, PAX3 and MITF have been previously recognized. Herein, we report biallelic
      deletions in SOX10, a gene associated with Waardenburg syndromes type II and IV.
      The affected fetuses have a severe phenotype with a lack of fetal movement
      resulting in four-limb arthrogryposis and absence of palmar and plantar creases,
      white hair, dystopia canthorum, and in one case cleft palate and in the other a
      cardiac malformation.

PMID- 30113774
TI  - Redox signalling from NADPH oxidase targets metabolic enzymes and developmental
      proteins in Fusarium graminearum.
AB  - NADPH oxidase (NOX) is one of the sources of reactive oxygen species (ROS) that
      modulates the activity of proteins through modifications of their cysteine
      residues. In a previous study, we demonstrated the importance of NOX in both the
      development and pathogenicity of the phytopathogen Fusarium graminearum. In this
      article, comparative proteomics between the wild-type and a Nox mutant of F.
      graminearum was used to identify active cysteine residues on candidate redox
      sensing proteins. A two-dimensional gel approach based on labelling with
      monobromobimane (mBBR) identified 19 candidate proteins, and was complemented
      with a gel-free shotgun approach based on a biotin switch method, which yielded
      99 candidates. The results indicated that, in addition to temporal regulation, a
      large number of primary metabolic enzymes are potentially targeted by NoxAB
      generated ROS. Targeted disruption of these metabolic genes showed that, although
      some are dispensable, others are essential. In addition to metabolic enzymes,
      developmental proteins, such as the Woronin body major protein (FGSG_08737) and a
      glycosylphosphatidylinositol (GPI)-anchored protein (FGSG_10089), were also
      identified. Deletion of either of these genes reduced the virulence of F.
      graminearum. Furthermore, changing the redox-modified cysteine (Cys325 ) residue
      in FGSG_10089 to either serine or phenylalanine resulted in a similar phenotype
      to the FGSG_10089 knockout strain, which displayed reduced virulence and altered
      cell wall morphology; this underscores the importance of Cys325 to the function
      of the protein. Our results indicate that NOX-generated ROS act as intracellular
      signals in F. graminearum and modulate the activity of proteins affecting
      development and virulence in planta.

PMID- 30113775
TI  - [A brief history of syphilis. The disease through the art and the artist].
AB  - Considering its strong symbolic connotations and its rich history, syphilis could
      be regarded as the perfect example of venerian disease. It could also be seen as
      a representative disease of the whole medical history and the evolution of both
      medical ways of thinking and curing. In this work we will briefly discuss the
      history of the syphilitic disease and try to show how this condition has affected
      the life and works of some of the most famous artists of the 19th century.
      Moreover, we shall try to evoke the complex relationship between art and
      pathology.

PMID- 30113776
TI  - [Acute respiratory distress revealing antisynthetase syndrome].
AB  - Antisynthetase syndrome is a clinical entity characterized by specific anti
      aminoacyl-tRNA-synthetase antibodies usually associated with inflammatory
      myopathy and interstitial lung disease. The classic presentation of the pathology
      is the pulmonary interstitium involvment, wich commonly determines the global
      prognosis. The subsequent diagnosis of antisynthetase syndrome in patients with
      acute respiratory distress syndrome (ARDS) is unusual, even more so when a veino
      veinous (VV) extracorporeal membrane oxygenation (ECMO) is required. This article
      presents a clinical case of antisynthetase syndrome with severe ARDS successfully
      treated with immunosuppressive agents and ECMO.

PMID- 30113777
TI  - [A rare cause of cryptorchidism, the persistence of mullerian ducts syndrome].
AB  - The Persistent Mullerian Ducts Syndrome (PMDS) is a rare congenital syndrome. It
      is one of abnormalities of genito-sexual development that is found on the
      normally virilized boy (46XY). It is characterized by the development of both
      Wolf structures and Muller duct. The pathophysiology can be explained by an
      action deficit of the anti-mullerian hormone (AMH). Its clinical presentations
      vary depending on the localization of the testis and the associated symptoms. Its
      discovery is mostly fortuitous and generally made in per-operative surgery of
      cryptorchidism or inguinal hernia. Treatment should be surgical. It relies on two
      aspects : ensuring the testicular descent and performing the excision of the
      mullerian duct. The follow-up is identical to the cryptorchid testes and the
      fertility problems will be influenced by the surgical procedure as well as the
      timing of the treatment.

PMID- 30113778
TI  - [Acute cytomegalovirus proctitis in a immunocompetent patient].
AB  - Cases of CMV proctitis are frequently reported in immunocompromised patients.
      However, some cases of CMV proctitis are linked to a CMV primary infection and to
      unprotected anal intercourse in immunocompetent patients. The most common symptom
      is bloody diarrhea (hemorrhagic colitis). The endoscopic exam can present in
      distincts forms. The diagnostic is based on a set of clinical, biological,
      endoscopic and histological arguments. The prognosis of the disease is favorable.
      The treatment is supportive. A research on other sexually transmitted diseases
      must be conducted.

PMID- 30113779
TI  - [A disseminated strongyloidiasis in a non immunocompromised patient].
AB  - Strongyloidiasis is a parasitosis mainly located in tropical and subtropical
      regions. Its European incidence is increasing due to population migration. The
      symptomatology is variable, largely depending on the host immune status. The
      diagnosis may be challenging as a specific inquiry is needed. The disseminated
      status, called hyperinfection syndrome, is a life-threatening disease that might
      occur in immunosuppressed patients. The patient's chances for a successful
      outcome depend on a quick and specific management. The treatment is based on
      anthelminthic agents such as ivermectine or albendazole for which the dosage will
      vary according to the infection type.

PMID- 30113780
TI  - [Mediastinitis following EBUS : about a complication after a minimally invasive
      investigation].
AB  - Endobronchial ultrasound (EBUS) is a minimally invasive investigation method that
      permits transbronchial needle aspiration (TBNA) of mediastinal and hilar
      lymphadenopathies in order to determine their etiology. Its indications are
      notably lung cancer staging and lymphadenopathy exploration in case of
      sarcoidosis and malignant lymphomas. The employment of EBUS-TBNA has grown over
      the past few years and has become an alternative to mediastinoscopy due to a
      lower complication rate. However, in rare cases, complications can occur as
      hemorrhage, infections (mediastinitis, pneumonia, pericarditis, cyst infection,
      sepsis) or other (pneumothorax, pneumomediastinitis). We report herein a case of
      a mediastinitis after endobronchial ultrasound-guided transbronchial needle
      aspiration which occurred in a 63-year-old patient treated by methotrexate and
      methylprednisolone for a rheumatoid arthritis. The symptoms appeared as fever and
      progressive dyspnea some days after the endoscopic procedure.

PMID- 30113781
TI  - [Acute myocardial infarction due to polycythemia vera].
AB  - We report the clinical case of a patient presenting with an acute myocardial
      infarction with ST- segment elevation. The patient is affected by polycythemia
      vera for many years and doesn't have any other cardiovascular risk factors. The
      frequency of thrombotic events in polycythemia vera (and more particularly
      myocardial infarction), their predictive factors, pathophysiology and treatment
      will be discussed.

PMID- 30113782
TI  - [Giant adrenal cyst].
AB  - Adrenal cysts are a rare entity which makes their treatment somewhat tough.
      Discovered in a fortuitous way or in the course of explorations for very
      aspecific symptoms, it is necessary to decide on a case-by-case basis, and after
      a careful clinical examination, whether the lesion is to be treated through
      surgery or if a follow-up iconography is sufficient. Three main parameters will
      influence this choice: the functional status of the cyst, its malignant potential
      and the potential complications related to the cyst. Current recommendations
      suggest a surgical treatment for all symptomatic cysts, for functional cysts, for
      cysts with a diameter exceeding 5 cm, for hemorrhagic cysts and for cysts with
      malignant imaging potential. The progress and surgical advantages brought by the
      development of laparoscopy make it the first technique to be chosen.

PMID- 30113783
TI  - [Pseudomyxoma peritonei : a cause of ascites that should not be underestimated].
AB  - Pseudomyxoma peritonei (PMP) is a rare condition that refers to a clinical
      syndrome resulting from the accumulation of mucin in the peritoneal cavity. It
      results from the intraperitoneal rupture of a mucinous epithelial neoplasm which
      is classically appendiceal. The prognosis of a limited appendiceal tumor is
      favourable. Nevertheless, in the case of peritoneal dissemination, the prognosis
      could be different according to the histological type and therapeutic management.
      We report the case of a 71-year-old female patient who developed a pseudomyxoma
      peritonei originating from an appendiceal adenocarcinoma.

PMID- 30113784
TI  - [Chemical peritonitis complicating the spontaneous rupture of a dermoid cyst of
      the ovary].
AB  - Mature ovarian teratoma is the most frequent benign tumor in premenopausal women.
      It is usually asymptomatic but complications are possible such as adnexal
      torsion, infection, malignant transformation or cystic rupture. The latter can be
      spontaneous or more often occurs during surgery of excision of dermoid cyst. It
      can rarely result in chemical peritonitis, which is due to the irritation of the
      peritoneal serosa by the aseptic content of the tumour. We report the case of a
      patient who undrewent an emergency laparotomy for a chemical peritonitis
      following a spontaneous rupture of a dermoid cyst. Afterwards, she developed an
      acute respiratory distress syndrome that required an admission in the intensive
      care unit and subsequent surgery.

PMID- 30113785
TI  - [Primary malignant melanoma of vagina].
AB  - The primary vaginal melanoma is a rare aggressive tumour with a poor prognosis.
      The average age at diagnosis is 60, and there are no known risk factors. The
      establishment of a classification system and treatment protocols are made
      difficult because there are so few cases. The 5-year survival rate is estimated
      at no more than ten per cent. We report a case of an inoperable primary vaginal
      melanoma in a 58-year old woman. There were metastatic lymph nodes in the lumbo
      aortic region, but no extension to bone or viscera. She was treated with
      nivolumab as monotherapy. Clinical and radiological evolution were both
      favourable, and the treatment was well tolerated.

PMID- 30113786
TI  - [Atypical metastasis from a colorectal cancer : the pons is undermined !]
AB  - Brain metastases occur in 1 to 4 % of patients with colorectal cancer and are
      unique in 0.5 % of them. Because of their infrequent nature, brain imaging is not
      recommended in the systematic follow-up of these patients. We report here an
      exceptional case of a unique brain metastasis in a very unusual position. An 82
      year-old patient with a colorectal cancer of the splenic angle that was treated
      with surgery and adjuvant chemotherapy, developed a series of neurological
      symptoms over four to six weeks: difficulty swallowing, loss of strength in the
      four limbs and balance disorders. These symptoms urged the performance of a
      nuclear magnetic resonance to exclude a central neurological lesion. MRI revealed
      a nodular tumor of 20 millimeters in the major transverse axis and 17 millimeters
      in the cerebro-caudal axis, located on the ventral portion of the protuberance.
      Because of its localization, surgery was not possible and the lesion was treated
      with Cyberknife radiosurgery. Thanks to the treatment, the lesion decreased in
      size and the symptoms improved significantly. Despite an initially very poor
      prognosis in view of the localization of the metastasis, the patient is alive and
      in excellent general condition more than eight months after the diagnosis of
      recurrence.

PMID- 30113787
TI  - [Acute myopic shift call sign of hantavirus infection].
AB  - Acute myopic shift may be the first symptom of a hantavirus infection. In
      Belgium, lethal infections are rare, but this illness has to be ruled out in the
      emergency room. The refractive shift has not clearly been explained yet. The
      ancillary tests to describe this phenomenon are not always performed. This
      article may help on how to manage and how to explore this disease.

PMID- 30113788
TI  - [Painful Horner's syndrome revealing carotid artery dissection : about four
      cases].
AB  - We report four cases of painful Horner's syndrome due to carotid artery
      dissection. A lesion on oculosympathic pathway causes Horner's syndrome. A
      painful Horner's syndrome needs a prompt exploration by tomodensitometry or
      magnetic resonance imaging to exclude carotid artery dissection. Actually,
      carotid artery dissection leads to stroke or cerebral ischemic symptoms, mainly
      in the first two weeks. The treatment is based on anticoagulants or antiplatelet
      agents.

PMID- 30113789
TI  - Results of a two year dental health education program to reduce dental caries in
      young Aboriginal children in New South Wales, Australia.
AB  - OBJECTIVE: To assess the effectiveness of a dental health education program,
      'Smiles not Tears' in preventing Early Childhood Caries in young Aboriginal
      children. BASIC RESEARCH DESIGN: Community trial. CLINICAL SETTING: Aboriginal
      Community Controlled Health Services in rural, remote and metropolitan areas in
      New South Wales, Australia. PARTICIPANTS: Aboriginal families who had a child six
      months of age. INTERVENTIONS: Aboriginal Health Workers from eight Aboriginal
      Community Controlled Health Services in rural, remote and metropolitan areas in
      New South Wales recruited Aboriginal families with young children to participate
      in the Smiles not Tears dental education program. A convenience sample of
      Aboriginal children from the same communities was recruited to form a historical
      control group. MAIN OUTCOME MEASURES: The caries prevalence at 30 months of age
      compared to children of a similar age in the control group. RESULTS: More
      children in the test group were caries free (n =104; 97.2%) when compared to the
      historical control group (n = 54; 65.9%). Only three children in the test group
      had caries which is less than the control group (n = 29). CONCLUSION: These
      results suggest that the Smiles not Tears dental education program has a positive
      impact on reducing the caries prevalence in young Aboriginal children.

PMID- 30113790
TI  - Nursing students' experiences of delivering dementia friends sessions to peers.
AB  - BACKGROUND: Nursing students and registered nurses often feel underprepared for
      their roles in dementia care. Extracurricular activities offer nursing students
      additional opportunities for professional development. A student-academic
      partnership initiative was developed in which nursing students delivered dementia
      friends sessions to their peers before formal taught content. AIM: To explore
      dementia champion nursing students' experiences, identify factors that affect
      collaborative working and make recommendations for future student-academic
      partnership projects. METHOD: In individual and dual interviews, three students
      were asked about their experiences of participating in the initiative. Interviews
      were recorded, transcribed and analysed using a thematic analysis framework.
      FINDINGS: Four themes were identified: commitment to working with people who have
      dementia, difficulties in taking on extracurricular responsibilities, personal
      development, and relationships and collaboration. CONCLUSION: Students were
      motivated by the need to provide high-quality dementia care. They identified
      benefits of collaborative working including development of time management, team
      working, leadership, communication and presentation skills. Future projects
      should take into account student workloads and offer rewards that are congruent
      with nursing students' values.

PMID- 30113791
TI  - [Paradigm shift in management of patients with vertigo and imbalance].
AB  - Dizziness is one of the most common causes of medical visits. Management of the
      dizzy patient may be challenging both for the general practitioner, in emergency
      departments, and special clinics, as behind a seemingly homogeneous clinical
      presentation several very different etiologies may occur. Research of the last
      two century enriched our knowledge about physiology and pathophysiology of the
      vestibular system. Much knowledge is now available about the labyrinth being able
      to sense head motions and gravity, processing of afferent vestibular stimuli,
      reflectory oculomotor and postural control, or recovery of the vestibular system.
      Based on scientific results new beside tests have been introduced including
      provocation maneuvers for detecting ectopic otoliths in different semicircular
      canals, head impulse test to examine function of the vestibulo-ocular reflex, and
      the HINTS+ battery for differentiation of peripheral or central origin of an
      acute vestibular syndrome. Technical innovations like videooculography and
      vestibular evoked myogenic potentials enable us to selectively and side
      specifically examine the function of all six semicircular canals and two otolith
      organs. Pathomechanism of disorders with vertigo and dizziness became more clear
      resulting in the development or amendment of diagnostic criteria of several
      vestibular disorders including vestibular migraine, Meniere's disease, benign
      paroxysmal positional vertigo, persistent postural-perceptual dizziness,
      bilateral vestibulopathy. Broader knowledge about the pathomechanism promoted the
      development of new therapeutic methods like different repositioning maneuvers in
      benign paroxysmal positional vertigo, pharmaceutical therapies, vestibular
      rehabilitation, and psychotherapy. We aimed to summarize the novelties in the
      field of oto-neurology.

PMID- 30113792
TI  - Isocitrate dehydrogenase mutations in defining the biology of and supporting
      clinical decision making in glioblastoma.
AB  - Background and purpose: Oncogenesis is related to a sequential accumulation of
      somatic mutations. Comprehensive characterizations of the genomic landscapes have
      been completed recently for several tumors, glioblastoma being among the first
      ones. Our own translational research studies have been focused on defining
      molecular subtypes of glioblastoma in the clinical setting because of an expected
      prognostic and therapeutic utility of the information. Somatic mutations in genes
      of the isocitrate dehydrogenase (IDH) enzyme family appear to be among the best
      defined biomarkers that also influence tumor behavior and confer clinical
      utility. Methods: We have reviewed the literature including our own results to
      summarize basic science and clinical correlates of IDH mutations. Results: The
      surveyed data reveal genomic, transcriptomic, epigenomic and biochemical
      consequences of IDH mutations in the context of glioblastoma biology and
      phenotype. In addition, a few studies highlight the therapeutic potential of
      targeting IDH, although thus far all tests have only been conducted in the
      preclinical setting. Conclusion: Somatic mutations in isoforms of IDH genes
      represent important biomarkers that correlate with biochemical, biological and
      phenotypic features of glioblastoma, and may also facilitate the development of
      new therapeutic strategies complementing the currently available approved
      protocols.

PMID- 30113793
TI  - [Strategies of using the new antiepileptic drugs for epilepsy in adults].
AB  - The new antiepileptic drugs have not changed the basic pharmacological treatment
      principles of epilepsy, but they have given greater choice in focal and in
      generalized epilepsies as well. The new drugs are not necessarily more effective
      than traditional drugs, but they have favourable pharmacokinetic characteristics,
      fewer interactions and better adverse effect profile in the acute and chronic
      phase of the treatment. They generally show a lower teratogenicity risk than the
      standard antiepileptics, although carbamazepine, one of the standard drugs can be
      used and zonisamide, a new one must be avoid in pregnancy. Due to characteristics
      mentioned above they are not only effective as add-on therapy, but in monotherapy
      as well. On the basis of the international and national recommendation
      lamotrigine and levetiracetam belong to the first line antiepileptics. The
      favourable tolerability of the new antiepileptics may improve the patient's
      compliance and adherence to the given treatment. The low teratogenicity makes
      them especially suitable for the treatment of women of childbearing age. The new
      antiepileptic drugs can succesfully used for the treatment of special patients'
      groups as for the post stroke, poszttraumatic epilepsies, for the epilepsies
      accompanied with brain tumours as well as for epilepsies in the elderly. The new
      drugs are advantageous for the treatment of such patients who have psychiatric
      symptoms or signs of cognitive decline and high risk of these symptoms
      respectively.

PMID- 30113794
TI  - [Early experience with minimal invasive treatment of thirty-one thoracolumbar
      injury cases].
AB  - The authors report on their experience with minimal invasive treatment of
      thirtyone thoracolumbar injury cases. The medical charts, radiological
      documentation (preop CT and MRI scans, postop CT scans at 3 and 6 months) were
      analysed retrospectively. All pedicle screws were inserted appropriately, there
      was no neurological deterioration or surgical site infection postoperatively.
      There were three cases of radiological loss of correction, however, these were
      clinically irrelevant. There were no screw loosening or implant failure observed.
      According to our experience, which coincedes with literature data, this minimally
      invasive percutaneous pedicle screw technique can be recommended for the
      treatment of thoracolumbar injury.

PMID- 30113795
TI  - Novel structured MRI reporting system in neonatal hypoxic-ischemic encephalopathy
      - issues of development and first use experiences.
AB  - Background and purpose: To develop an evidence-based, standardized structured
      reporting (SR) method for brain MRI examinations in neonatal hypoxic-ischemic
      encephalopathy (HIE) suitable both for clinical and research use. Methods: SR
      template development was based on comprehensive review of the pertinent
      literature with the basic sections and subdivisions of the template defined
      according to MRI sequences (both conventional and diffusion-weighted, MR
      spectroscopy (MRS), and T2*-weighted imaging), and the items targeted on age
      related imaging patterns of HIE. In order to evaluate the usability of the
      proposed SR template we compared data obtained from the brain MR image analysis
      of 87 term and 19 preterm neonates with the literature. The enrolled 106 infants
      were born between 2013 and 2015, went through therapeutic hypothermia according
      to the TOBY criteria due to moderate to severe asphyxia and had at least one
      brain MRI examination within the first two weeks of life. Ethical approval was
      obtained for this retrospective study. Descriptive statistical analysis was also
      performed on data exported from the structured reporting system as feasibility
      test. Results: The mean gestational age of the study population was 38.3+/-2.2
      weeks; brain MRI was performed on 5.8+/-2.9 day of life, hence in 78% of our
      patients after the conclusion of therapeutic hypothermia. Our main imaging
      findings were concordant to the pertinent literature. Moreover, we identified a
      characteristic temporal evolution of diffusion changes. Interestingly 18%
      (n=19/106) of the clinically asphyxiated infants had isolated axial-extraaxial
      haemorrhage without any imaging sign of HIE. Conclusion: In this article our
      approach of reporting HIE cases with our novel SR template is described. The SR
      template was found suitable for reporting HIE cases, moreover it uncovered time
      and location dependent evolution of diffusion abnormalities (and
      pseudonormalization, as well), suggesting its usefulness in clinical research
      applications. The high number of isolated intracranial haemorrhages, and the
      changing diffusion pattern emphasizes the importance of early imaging in HIE.

PMID- 30113796
TI  - Can high uric acid levels be an independent risk factor for acute ischemic stroke
      due to large-artery atherosclerosis?
AB  - Background and purpose: Uric acid is a molecule that is known to act as a natural
      antioxidant in acute oxidative stress conditions such as acute ischemic stroke
      (AIS). Although there are several studies on the prognostic value of serum uric
      acid (UA) level, especially the AIS, its importance in ischemic stroke is still
      controversial. Our aim in this study is to investigate whether the serum UA level
      is an indicative biomarker in the large-artery atherosclerosis in the AIS
      etiology. Methods: Of the patients admitted to Sakarya University Training and
      Research Hospital Department of Neurology between January 2017 and November 2017,
      91 hospitalized patients, who had AIS diagnosis and had their uric acid levels
      measured, were analyzed retrospectively. Patients with diabetes mellitus (DM),
      hypertension (HT), smoking habit, obesity, gout, hyperlipidemia (HL) and renal
      failure were excluded from the study. Patients were classified as anterior system
      and posterior system infarct. Then, patients were divided into two groups, one
      with internal carotid artery (ICA) > 50% stenosis and the other with ICA < 50%
      stenosis according to carotid-vertebral artery doppler USG examination performed
      for etiology. Serum UA, total bilirubin, direct bilirubin and indirect bilirubin
      levels of both groups were statistically compared. Results: In the comparison of
      serum UA values of ICA>50% stenosis and ICA<50% stenosis group of AIS patients, a
      statistically significant difference was found between the UA levels (p<0.000),
      but there was no difference between total bilirubin, direct bilirubin and
      indirect bilirubin values (p>0.05). Conclusion: High uric acid levels can be
      considered an independent, indicative risk factor for large-artery disease in
      AIS.

PMID- 30113797
TI  - Atypical type of Hirayama disease: Onset of proximal upper extremity.
AB  - Hirayama disease is a rare, benign motor neuron disease. It has been proposed
      that the dura mater's posterior wall lacks sufficient elasticity in the lower
      cervical region and this causes the tense dura part to displace anteriorly upon
      flexion. The disease is described as involving unilateral upper extremity with a
      distal-onset. We reported weakness and atrophy of the proximal part of an
      extremity in a 45-year-old man who is diagnosed with Hirayama disease. Proximal
      onset is a rare type of Hirayama Disease. Clinicians must be alert of proximal
      involvement and the diagnosis should be confirmed with electrophysiological and
      flexion MRI studies.

PMID- 30113798
TI  - [Clinical characteristics of early juvenile GM2 gangliosidosis: a case report].
AB  - We describe the case of a 15-year-old male with early juvenile type GM2
      gangliosidosis. He first manifested with progressive clumsiness in his
      extremities at the age of 1.5 years, followed by motor regression. Intellectual
      disability became evident as late as age 6 years. This discrepancy along with
      rapid motor deterioration after varicella infection, lack of startle response or
      macrocephaly, and paucity of myoclonus were thought to be characteristic of
      juvenile GM2 gangliosidosis. In contrast to the cerebellar atrophy as the initial
      finding in usual juvenile GM2 gangliosidosis, magnetic resonance imaging revealed
      initially cerebral, and subsequently cerebellar, progressive atrophy. Autistic
      behavioral problems, including phonophobia, during intellectual regression in
      this patient was also unusual in juvenile GM2 gangliosidosis. Thus, recognition
      of these features would prompt proper diagnosis and insights into the
      pathomechanisms of GM2 gangliosidosis.

PMID- 30113799
TI  - [Successful treatment with topiramate in a case of idiopathic intracranial
      hypertension refractory to acetazolamide].
AB  - A 6-year-old girl experienced nausea and vomiting for 3 weeks and double vision
      for 1 week prior to her first visit to our hospital. She had bilateral
      ophthalmoplegia from sixth cranial nerve palsy and papilledema. Her brain MRI
      showed normal brain parenchyma. The lumbar cerebrospinal fluid (CSF) opening
      pressure was 1000 mm of water measured with normal CSF contents. From these
      findings, she was diagnosed with idiopathic intracranial hypertension (IIH).
      Initial lumbar puncture (LP) immediately improved her symptoms, but
      acetazolamide, a first line drug for the treatment of IIH, failed to maintain the
      remission, and three more periodical LP were required to relieve her symptoms
      every 2 weeks. After the fourth LP, acetazolamide was switched to a second line
      drug for IIH, topiramate, which was found to be highly effective in controlling
      IIH in a short time period. The long process of IIH causes vision loss,
      therefore, its prompt treatment is vital. In cases refractory to medical
      treatment, surgical treatments such as CSF shunt are considered. Acetazolamide is
      used in most IIH cases after the initial diagnosis, but in this case, it was
      ineffective, and topiramate was highly effective. Both acetazolamide and
      topiramate are inhibitors of carbonic anhydrase isoforms involved in CSF
      secretion. Inhibition of choroid plexus carbonic anhydrase by these drugs leads
      to decreased CSF secretion and the consequent control of intracranial pressure.
      Higher isoform specificity and increased lipophilic nature of topiramate, which
      are advantageous for passing through the blood brain barrier, may be the reasons
      for better activity than acetazolamide, at least in the present case. Topiramate
      might be effective and should be considered for refractory IIH cases before
      surgical treatments.

PMID- 30113801
TI  - Harnessing CRISPR Effectors for Infectious Disease Diagnostics.
AB  - Nucleic acid detection is an important method for pathogen identification but can
      be expensive, have variable sensitivity and specificity, and require substantial
      infrastructure. Two new methods capitalize on unexpected in vitro properties of
      clustered regularly interspaced short palindromic repeats (CRISPR) effectors,
      turning activated nucleases into intrinsic amplifiers of a specific nucleic-acid
      binding event. These effectors are coupled with a variety of reporters and used
      in tandem with existing isothermal amplification methods to produce sensitive,
      sequence-specific pathogen identification in multiple field-deployable formats.
      While still in their infancy, these modular CRISPR-based methods have the
      potential to transform pathogen identification and other aspects of infectious
      disease diagnostics.

PMID- 30113800
TI  - Facile Access to Wearable Device via Microfluidic Spinning of Robust and Aligned
      Fluorescent Microfibers.
AB  - Microfluidic spinning technology (MST) has drawn much attention owing to its
      ideal platform for ordered fluorescent fibers, along with their large-scale
      manipulation, high efficiency, flexibility, and environment friendliness. Here,
      we employed the MST to fabricate a series of uniform fluorescent microfibers. By
      adjusting the microfluidic spinning parameters, the as-prepared microfibers of
      different diameters are successfully obtained. For more practice, these regular
      arranged fibers could be formed to versatile fluorescent codes by using various
      microfluidic chips. Also, these versatile fluorescent fibers could be further
      weaved into a white fluorescent film via continuous and cross-spinning process,
      which could be applied in a white light emitting diode (WLED) and a wearable
      device. Besides, we investigated the MST-directed microreactors to carry out
      green synthesis of CdSe quantum dots (QDs) fibers by the knot of Y-type
      microfluidic chip. The as-prepared CdSe QDs show nice optical property and are
      good candidate as phosphors in WLED. This strategy offers a facile and
      environment-friendly route to fluorescent hybrid microfibers and might open their
      potential application in optical devices, security, and fluorescent coding.

PMID- 30113802
TI  - Inorganic "Conductive Glass" Approach to Rendering Mesoporous Metal-Organic
      Frameworks Electronically Conductive and Chemically Responsive.
AB  - A representative mesoporous metal-organic-framework (MOF) material, NU-1000, has
      been rendered electronically conductive via a robust inorganic approach that
      permits retention of MOF crystallinity and porosity. The approach is based on
      condensed-phase grafting of molecular tin species onto the MOF nodes via
      irreversible reaction with hydroxyl and aqua ligands presented at the node
      surface, a self-limiting process termed solvothermal installation (of metal ions)
      in MOFs (SIM, a solution-phase analog of atomic layer deposition in MOFs).
      Treatment of the modified MOF with aerated steam at 120  degrees C converts the
      grafted tin molecules to tetratin(IV)oxy clusters, with the clusters being sited
      between insulating pairs of zirconia-like nodes (the zirconium component being
      key to endowing the parent material with requisite chemical and thermal
      stability). By introducing new O-H presenting ligands on the modified-MOF node,
      the high-temperature steam step additionally serves to reset the material to
      reactive form, thus enabling a second self-limiting tin-grafting step to be run
      (and after further steam treatment, enabling a third). Difference-envelop-density
      (DED) analyses of synchrotron-derived X-ray scattering data, with and without
      installed tin species, show that the clusters formed after one cycle are
      spatially isolated, but that repetitive SIM cycling adds metal and oxygen ions in
      a way that enshrouds nodes, links clusters, and yields continuous one-dimensional
      strands of oxy-tin(IV), oriented exclusively along the c axis of the MOF. Two
      probe conductivity measurements show that the parent MOF and the version
      containing isolated oxy-tin(IV) clusters are electrically insulating, but that
      the versions featuring continuous strands show an electrical conductivity of 1.8
      * 10-7 S/cm after three Sn-SIM cycles. When combined with interdigitated
      microelectrodes, the solvent-free and conductive-glass-modified material (three
      Sn-SIM cycles) displays a substantial and persistent increase in electrical
      conductivity during exposure to 5% H2, indicating a role for dissociated H2 as an
      electronic dopant. The increase can be repetitively reversed by alternating H2
      with air, illustrating the ability of the conductive MOF to function as a
      resistive sensor for H2 and suggesting further potential applications that may
      capitalize on the combination of high volumetric surface area, high mesoporosity,
      high chemical and thermal stability, and significant electrical conductivity.

PMID- 30113803
TI  - Performance Enhancement of Mesoporous TiO2-Based Perovskite Solar Cells by SbI3
      Interfacial Modification Layer.
AB  - TiO2 is commonly used as an electron-transporting material in perovskite
      photovoltaic devices due to its advantages, including suitable band gap, good
      photoelectrochemical stability, and simple preparation process. However, there
      are many oxygen vacancies or defects on the surface of TiO2 and thus this affects
      the stability of TiO2-based perovskite solar cells under UV light. In this work,
      a thin (monolayer) SbI3 modification layer is introduced on the mesoporous TiO2
      surface and the effect at the interface between of TiO2 and perovskite is
      monitored by using a quartz crystal microbalance system. We demonstrate that the
      SbI3-modified TiO2 electrodes exhibit superior electronic properties by reducing
      electronic trap states, enabling faster electron transport. This approach results
      in higher performances compared with electrodes without the SbI3 passivation
      layer. CH3NH3PbI3 perovskite solar cells with a maximum power conversion
      efficiency of 17.33% in air, accompanied by a reduction in hysteresis and
      enhancement of the device stability, are reported.

PMID- 30113804
TI  - Integration of Nanomaterials into Three-Dimensional Vertical Architectures.
AB  - A novel layer-by-layer three-dimensional (3D) architecture allowing one to expand
      device fabrication in the vertical direction and integrating functional
      nanomaterials is presented by emulating civil engineering. The architecture uses
      SU-8 pillars as structural columns, which support multiple horizontal suspended
      thin films. The films then serve as platforms for the integration of
      nanomaterials and nanodevices. Multiple graphene layers suspended across SU-8
      pillars with precise control on their vertical spacing are demonstrated. In
      addition to graphene, silicon nitride films that offer high strength yield and
      thickness control are also presented. Metallic microstructures, plasmonic
      nanostructures, semiconducting quantum dots, and monolayer graphene on the
      suspended films are achieved to prove the capability of integrating functional
      nanomaterials. This work provides the potential to integrate highly compact
      micro/nanoscale devices at different vertical levels with high surface density,
      which allows for more capabilities and functionalities in a single device.

PMID- 30113805
TI  - Multiscale Functional Imaging of Interfaces through Atomic Force Microscopy Using
      Harmonic Mixing.
AB  - The spatial resolution of atomic force microscopy (AFM) needed to resolve
      material interfaces is limited by the tip-sample separation ( d) dependence of
      the force used to record an image. Here, we present a new multiscale functional
      imaging technique that allows for in situ tunable spatial resolution, which can
      be applied to a wide range of inhomogeneous materials, devices, and interfaces.
      Our approach uses a multifrequency method to generate a signal whose d-dependence
      is controlled by mixing harmonics of the cantilever's oscillation with a
      modulated force. The spatial resolution of the resulting image is determined by
      the signal's d-dependence. Our measurements using harmonic mixing (HM) show that
      we can change the d-dependence of a force signal to improve spatial resolution by
      up to a factor of two compared to conventional methods. We demonstrate the
      technique with both Kelvin probe force microscopy (KPFM) and bimodal AFM to show
      its generality. Bimodal AFM with harmonic mixing actuation separates conservative
      from dissipative forces and is used to identify the regions of adhesive residue
      on exfoliated graphene. Our electrostatic measurements with open-loop KPFM
      demonstrate that multiple force modulations may be applied at once. Further, this
      method can be applied to any tip-sample force that can be modulated, for example,
      electrostatic, magnetic, and photoinduced forces, showing its universality.
      Because HM enables in situ switching between high sensitivity and high spatial
      resolution with any periodic driving force, we foresee this technique as a
      critical advancement for multiscale functional imaging.

PMID- 30113806
TI  - Plasmon Coupling Effect-Enhanced Imaging of Metal Ions in Living Cells Using
      DNAzyme Assembled Core-Satellite Structures.
AB  - We demonstrate a core-satellite plasmonic nanoprobe assembled via metal-ion
      dependent DNA-cleaving DNAzyme linker for imaging intercellular metal ion based
      on plasmon coupling effect at a single-particle level. As metal ions are present
      in the system, the DNAzyme linker will be cleaved, and thus, disassembly of the
      core-satellite nanoprobes occurs, which results in distinct blue shift of the
      scattering spectra of Au core-satellite probes and naked color change of the
      scattering light. This change in scattering spectra has been supported by
      theoretical simulations. As a proof of concept, sensitive detection of Cu2+ with
      a limit of detection down to 67.2 pM has been demonstrated. The nanoprobes have
      been further utilized for intracellular Cu2+ imaging in living cells. The results
      demonstrate that the present strategy provides a promising platform for detection
      and imaging of metal ions in living cells and could be potentially applied to
      imaging other interesting target molecules simply by substituting the
      oligonucleotide sequence.

PMID- 30113807
TI  - Microfluidic Fabrication of Bioinspired Cavity-Microfibers for 3D Scaffolds.
AB  - We present a gas-in-water microfluidic method to precisely fabricate well
      controlled versatile microfibers with cavity knots (named cavity-microfiber),
      like tiny-cavity-microfiber, hybrid-cavity-microfiber, cavity-microfiber, and
      chained microfiber. The cavity-microfibers are endowed with tunable morphologies,
      unique surface properties, high specific surface area, assembling ability,
      flexibility, cytocompatibility, and hydroscopicity. We assemble cavity
      microfibers as 3D scaffolds for culturing the human umbilical vein endothelial
      cells (HUVECs) and dehumidifying. The HUVECs on the scaffolds demonstrate good
      cell viability and 3D HUVECs frameworks, confirming the unique cytocompatibility
      of cavity-microfiber. And the cavity-microfibers and their scaffolds also
      demonstrate excellent dehumidifying ability and large-scale dehumidifying,
      respectively. Our cavity-microfiber can offer a broad range of applications in
      sensor, wearable electronics, dehumidifying, water collection engineering, drug
      delivery, biomaterials, and tissue engineering.

PMID- 30113808
TI  - Electrochemical Behaviors of a Vapor-Phase Polymerized Conductive Polymer Coated
      on LiV3O8 in Li-Metal Rechargeable Batteries.
AB  - A new coating method called vapor-phase polymerization (VPP) is used to coat a
      conductive polymer on LiV3O8 (LVO) surfaces for the first time in lithium-metal
      secondary batteries to protect the interface layer and enhance the
      electrochemical properties of the cathode. The VPP method can be used to coat an
      appropriate amount of the polymer and homogeneously coat the LVO active material
      surfaces because of the use of vapor-phase monomers. The presence of the coating
      layer was confirmed by X-ray photoelectron spectroscopy, Fourier transform
      infrared spectroscopy, and transmission electron microscopy. Polymer coating of
      LVO by VPP results in enhanced cyclic stability and rate capability at various C
      rates. At 0.2 C-rate, it has high specific capacities of 254.7 and 272.2 mA h g-1
      in the first and second cycles, respectively. Further, the capacity retention is
      94.6% from the 2nd cycle to the 100th cycle. The improved electrochemical
      performance is attributed to the homogeneously conductive polymer formed by VPP,
      which can improve the electrical conductivity of the active material and inhibit
      dissolution by preventing direct contact with the electrolyte.

PMID- 30113809
TI  - Matrix Vesicles-Containing Microreactors as Support for Bonelike Osteoblasts to
      Enhance Biomineralization.
AB  - Therapeutic cell mimicry aims to provide a source of cell-like assemblies, which
      exhibit the core structural or functional properties of their natural
      counterparts with broad envisioned applications in biomedicine. Bone tissue
      engineering (BTE) aims at promoting and inciting the natural healing process of,
      for instance, critically sized bone defects. Microreactors designed to co
      assemble with biological bone-forming osteoblasts like SaOS-2 cells to start
      biomineralization are reported for the first time. The alginate-based
      microparticles are equipped with active alkaline phosphatase-loaded artificial
      liposomes or SaOS-2-derived matrix vesicles (MVs). Spheroids assembled from SaOS
      2 cells and microreactors not only exhibit higher cell viability, but also show
      enhanced biomineralization when MVs are present. The active biomineralization
      stimulation of the microreactors is illustrated by colorimetric calcium
      quantification and micro-computed tomography. These findings show the promising
      potential of applying cell mimicry in BTE.

PMID- 30113810
TI  - Natural Brain Penetration Enhancer-Modified Albumin Nanoparticles for Glioma
      Targeting Delivery.
AB  - The unsatisfactory therapeutic outcome for glioma is mainly due to the poor blood
      brain barrier (BBB) permeability and inefficient accumulation in the glioma area
      of chemotherapeutic agents. The existing drug delivery strategies can increase
      drug transport to the brain but are restricted by side effects and/or poor
      delivery efficiency. In this study, potent brain penetration enhancers were
      screened from the active components of aromatic resuscitation drugs used in
      traditional Chinese medicine. A novel glioma-targeting system based on enhancer
      modified albumin nanoparticles was developed to safely and efficiently deliver
      drugs to the glioma regions in the brain. The nanoparticles improved the
      transport of nanoparticles across brain capillary endothelial cell (BCEC)
      monolayer by increasing endocytosis in endothelial cells and causing BBB
      disruption. In vivo imaging studies demonstrated that the systems could enter the
      brain and subsequently accumulate in glioma cells with a much higher targeting
      efficiency than that of transferrin-modified albumin nanoparticles. Of note, the
      nanoparticles could be captured and penetrate through endothelial cells fenestrae
      in pineal gland, which is suggestive of an effective way to deliver a nanosystem
      to the brain by bypassing the BBB. The nanoparticles showed good biocompatibility
      and negligible cytotoxicity. The results reveal an efficient and safe strategy
      for brain drug delivery in glioma therapy.

PMID- 30113811
TI  - Catalyst Support Effect on the Activity and Durability of Magnetic Nanoparticles:
      toward Design of Advanced Electrocatalyst for Full Water Splitting.
AB  - Earth-abundant element-based inorganic-organic hybrid materials are attractive
      alternatives for electrocatalyzing energy conversion reactions. Such material
      structures do not only increase the surface area and stability of metal
      nanoparticles (NPs) but also modify the electrocatalytic performance. Here, we
      introduce, for the first time, multiwall carbon nanotubes (MWNTs) functionalized
      with nitrogen-rich emeraldine salt (ES) (denoted as ES-MWNT) as a promising
      catalyst support to boost the electrocatalytic activity of magnetic maghemite
      (gamma-Fe2O3) NPs. The latter component has been synthesized by a simple and
      upscalable one-step pulsed laser ablation method on Ni core forming the core
      shell Ni@gamma-Fe2O3 NPs. The catalyst (Ni@gamma-Fe2O3/ES-MWNT) is formed via
      self-assembly as strong interaction between ES-MWNT and Ni@gamma-Fe2O3 results in
      NPs' encapsulation in a thin C-N shell. We further show that Ni does not directly
      function as an active site in the electrocatalyst but it has a crucial role in
      synthesizing the maghemite shell. The strong interaction between the NPs and the
      support improves notably the NPs' catalytic activity toward oxygen evolution
      reaction (OER) in terms of both onset potential and current density, ranking it
      among the most active catalysts reported so far. Furthermore, this material shows
      a superior durability to most of the current excellent OER electrocatalysts as
      the activity, and the structure, remains almost intact after 5000 OER stability
      cycles. On further characterization, the same trend has been observed for
      hydrogen evolution reaction, the other half-reaction of water splitting.

PMID- 30113812
TI  - Highly Durable and Flexible Transparent Electrode for Flexible Optoelectronic
      Applications.
AB  - A highly-durable, highly-flexible transparent electrode (FTE) is developed by
      applying a composite made of a thin metal grid and a doped conducting polymer
      onto a colorless polyimide-coated NOA63 substrate. The proposed FTE exhibits a
      transparency of 90.7% at 550 nm including the substrate and a sheet resistance of
      30.3 Omega/sq and can withstand both moderately high-temperature annealing (~180 
      degrees C) and acidic solution (70  degrees C, pH 0.3) processes without
      performance degradation. The fabricated FTE yielded good mechanical stability
      under 10 000 cycles of bending deformations at a bending radius less than 1 mm
      without degradation of electrical conductivity. The high durability of the
      proposed FTE allows for the fabrication of flexible energy harvesting devices
      requiring harsh conditions, such as highly flexible perovskite solar cells
      (FPSCs) with a steady-state power conversion efficiency (PCE) of 12.7%. Notably,
      93% of the original PCE is maintained after 2000 bending cycles at an extremely
      small bending radius of 1.5 mm. The FPSCs installed on curved surfaces of
      commercial devices drive them under various environments. The applicability of
      the proposed FTE is further confirmed via the fabrication of a flexible
      perovskite light-emitting diode. The proposed FTE demonstrates great potential
      for applications in the field of flexible optoelectronic devices.

PMID- 30113813
TI  - Graphene-Loaded Bi2Se3: A Conversion-Alloying-type Anode Material for Ultrafast
      Gravimetric and Volumetric Na Storage.
AB  - Sodium-ion battery (SIB) has been a promising alternative for sustainable
      electrochemical energy-storage devices. However, it still needs great efforts to
      develop electrode materials with ultrafast gravimetric and volumetric Na-storage
      performance, due to difficult balance between Na-ion diffusion kinetics and
      pressing density of materials. In this work, Bi2Se3/graphene composites,
      synthesized by a selenization reaction, are investigated as anode materials for
      SIBs. Na-ion storage mechanism of Bi2Se3 should be attributed to a combined
      conversion-alloying one by a series of ex situ measurements. In the composites,
      Bi2Se3 particles with an average diameter of 100 nm are uniformly dispersed onto
      graphene with strong interfacial interaction. Despite their nanoscale size, the
      pressing density of Bi2Se3/graphene composite could still reach a high value of
      2.07 g/cm3. Therefore, the composites can deliver a high gravimetric specific
      capacity of 346 mAh/g and volumetric specific capacity of 716 mAh/cm3 at a
      current density of 0.1 A/g. Remarkably, the composites exhibit an ultrafast Na
      storage capability and a negligible capacity fading with the increasing of
      current density from 0.2 to 5 A/g. Even at 10 A/g (~30 C), the composites still
      possess a gravimetric capacity of 183 mAh/g and volumetric capacity of 379
      mAh/cm3 with ultrastable cyclability up to 1000 cycles. This work introduces a
      valid route to design electrode materials with both excellent gravimetric and
      volumetric performance of Na-ion storage.

PMID- 30113814
TI  - Minimizing Context Dependency of Gene Networks Using Artificial Cells.
AB  - The functioning of synthetic gene circuits depends on their local chemical
      context defined by the types and concentrations of biomolecules in the
      surrounding milieu that influences gene transcription and translation. This
      chemical-context dependence of synthetic gene circuits arises from significant
      yet unknown cross talk between engineered components, host cells, and
      environmental factors and has been a persistent challenge for synthetic biology.
      Here, we show that the sensitivity of synthetic gene networks to their
      extracellular chemical contexts can be minimized, and their designed functions
      rendered robust using artificial cells, which are synthetic biomolecular
      compartments engineered from the bottom-up using liposomes that encapsulate the
      gene networks. Our artificial cells detect, interact with, and kill bacteria in
      simulated external environments with different chemical complexity. Our work
      enables the engineering of synthetic gene networks with minimal dependency on
      their extracellular chemical context and creates a new frontier in controlling
      robustness of synthetic biological systems using bioinspired mechanisms.

PMID- 30113815
TI  - Significantly Accelerated Osteoblast Cell Growth on TiO2/SrHA Composite Mediated
      by Phenolic Compounds (BHM) from Hippocamp us kuda Bleeler.
AB  - The microstructure of hydroxyapatite is known to influence cellular behavior, can
      be used as a substrate for osteoblast growth, and exploited as a drug-release
      platform. However, easy delamination and self-decomposition of hydroxyapatite
      caused by poor adhesion with substrates are the main problems currently. In this
      paper, we successfully fabricated titanium dioxide/strontium-doped hydroxyapatite
      (TiO2/SrHA) composite scaffolds by self-generated strontium-substituted
      hydroxyapatite microspheres in TiO2 nanotubes. Moreover, the active compound 1-(5
      bromo-2-hydroxy-methoxyphenyl)-ethanone (BHM) from Seahorse ( Hippocampus kuda
      Bleeler) was loaded in this scaffold, and the controlled release kinetics of BHM
      was studied. It was found that in the first 5 h, the release concentration and
      time of BHM had a good linear relationship, and the correlation coefficient
      reached 0.98. TiO2/SrHA/BHM composites exhibited favorable cytocompatibility at a
      given concentration of BHM (20 MUmol/L). Compared to pure SrHA, TiO2 nanotubes,
      and traditional TiO2/SrHA composites, superior cytocompatibility (cell adhesion
      and proliferation) of MC3T3-E1 was obtained on TiO2/SrHA/BHM composites. The
      expression levels of osteogenic marker genes such as alkaline phosphatase,
      osteopontin, osteocalcin, runt-related transcription factor 2, and collagen I are
      also upregulated to varying degrees. This TiO2/SrHA composite scaffold-mediated
      phenolic compound BHM could be applied in bone tissue repair.

PMID- 30113816
TI  - Electrochemical Characterization of Single Lithium-Ion Conducting Polymer
      Electrolytes Based on sp3 Boron and Poly(ethylene glycol) Bridges.
AB  - A novel series of single lithium-ion conducting polymer electrolytes (SLICPE)
      based on sp3 boron and poly(ethylene glycol) (PEG) bridges is presented, in the
      context of the development of a new generation of batteries, with the aim to
      overcome the problems related to concentration overpotential and low ion
      transport numbers in conventional solid polymer electrolytes (SPE). The phase
      separation generated by the physical mixture of SPE with plasticizers such as
      poly(ethylene oxide) is still a serious problem. In this work, the use of PEG
      with different chain lengths, for the polycondensation reaction with LiB(OCH3)4,
      to synthesize SLICPE allows preventing phase separation while tuning the
      predominant conduction mechanism, and thus the electrical properties, especially
      the lithium-ion transference number. The ionic transport is promoted by chain
      mobility as the chain length is increased. SLICPE with the best ionic
      conductivity values (4.95 +/- 0.05) * 10-6 S cm-1 was the one synthesized from
      poly(ethylene glycol) with an average MN of 400 (BEG8), having an O/Li+ ratio of
      20. The lithium transference number ( tLi+) and electrochemical stability window
      of SLICPE membranes at 25  degrees C decreased as the PEG bridge length between
      sp3 boron atoms increased from 0.97 to 0.88 and 5.4 to 4.2 V vs Li0/Li+,
      respectively, for SLICPE synthesized from PEG with an average MN of 50-400 (BEG1
      to BEG8).

PMID- 30113817
TI  - An EPR Investigation of Binding Environments by N-Donor Chelating Exchange Resins
      for Cu Extraction from Aqueous Media.
AB  - Chelating exchange resins (CERs) are now widely used for metal extraction in
      aqueous acidic media. Many of these CERs contain surface N-donor ligands, such as
      di(2-picolylamine) (BPA) and picolylamine (PA), which are highly selective for
      Cu(II) uptake. Two such widely used resins are Dowex M4195 and CuWRAM.
      Surprisingly, very little is known about the Cu(II) binding environments on the
      exchange resins, particularly at variable concentrations and pH's, and therefore
      we used EPR spectroscopy to investigate this binding. The broad EPR spectra of
      the Cu(II) loaded resins are quite complex, indicating the presence of multiple
      Cu(II) binding environments. By preparing a series of well-defined [CuII(PA) x]
      and [CuII(BPA) x] complexes and studying their EPR and UV-vis spectra, the
      individual Cu(II) species contributing to the broad and overlapping EPR spectra
      of the loaded resins were identified. For Dowex M4195, [CuII(BPA)](H2O) m and
      [CuII(BPA)2] complexes are most dominant, whereas for CuWRAM two dominant species
      including [CuII(PA)2](H2O) m and [CuII(PA)3] were identified. Notably,
      [CuII(PA)](H2O) m was not present in this sample. The experimental spin
      Hamiltonian parameters for all these species were in good agreement with the
      density functional theory derived values. Additional intermolecular Cu(II)
      species were identified on both resins, labeled [CuII(BPA) x(BPA) y(H2O) n] and
      [CuII(PA) x(PA) y(H2O) n]. The presence of coordinated water in these
      intermolecular anchored sites was confirmed in a series of dehydration
      rehydration experiments. Furthermore, a series of acid elution experiments also
      confirmed that these species are less strongly coordinated to the resins compared
      to the intramolecular species [CuII(BPA)](H2O) m, [CuII(BPA)2], [CuII(PA)2](H2O)
      m, and [CuII(PA)3]. Finally, while equilibrium batch uptake measurements revealed
      that the CuWRAM material had a much lower Cu(II) capacity compared to the
      polymeric Dowex material, the adsorbed copper can be recovered more efficiently
      using acid elution.

PMID- 30113818
TI  - Transgenerational Inheritance of DNA Hypomethylation in Daphnia magna in Response
      to Salinity Stress.
AB  - Epigenetic mechanisms have been found to play important roles in environmental
      stress response and regulation. These can, theoretically, be transmitted to
      future unexposed generations, yet few studies have shown persisting stress
      induced transgenerational effects, particularly in invertebrates. Here, we focus
      on the aquatic microcrustacean Daphnia, a parthenogenetic model species, and its
      response to salinity stress. Salinity is a serious threat to freshwater
      ecosystems and a relevant form of environmental perturbation affecting freshwater
      ecosystems. We exposed one generation of D. magna to high levels of salinity (F0)
      and found that the exposure provoked specific methylation patterns that were
      transferred to the three consequent nonexposed generations (F1, F2, and F3). This
      was the case for the hypomethylation of six protein-coding genes with important
      roles in the organisms' response to environmental change: DNA damage repair,
      cytoskeleton organization, and protein synthesis. This suggests that epigenetic
      changes in Daphnia are particularly targeted to genes involved in coping with
      general cellular stress responses. Our results highlight that epigenetic marks
      are affected by environmental stressors and can be transferred to subsequent
      unexposed generations. Epigenetic marks could therefore prove to be useful
      indicators of past or historic pollution in this parthenogenetic model system.
      Furthermore, no life history costs seem to be associated with the maintenance of
      hypomethylation across unexposed generations in Daphnia following a single stress
      exposure.

PMID- 30113819
TI  - Click Chemistry-Assisted Synthesis of a beta-d-Galactose-Targeted SiO2@RC Shell
      Core Structure as a Nanoplatform for Metal-Based Complex Delivery.
AB  - A facile reversed-phase microemulsion method was used to synthesize shell-core
      nanospheres of SiO2@RCs (SiO2-encapsuled rare-earth metal complexes). beta-d
      Galactose was then grafted onto the surfaces of the nanospheres through the
      copper(I)-catalyzed azide-alkyne cycloaddition click reaction for targeted
      delivery. The chemical characteristics and surface profiles of the nanocarriers
      were investigated by Fourier transform infrared spectroscopy, dynamic light
      scattering, transmission electron microscopy, and scanning electron microscopy. A
      high-efficiency microwave synthesis method was applied to prepare five complex
      cores by the reaction of different rare-earth metal salts with two isomeric
      ligands, o-CPA (2-chlorophenoxyacetic acid) and m-CPA (3-chlorophenoxyacetic
      acid). The crystal structures of the five synthesized RC cores were confirmed
      through X-ray diffraction, which revealed the formulas of five RCs, [Dy( o
      CPA)3(H2O)].H2O RC1, [Ho( o-CPA)3(H2O)].H2O RC2, 2[Er( m-CPA)3(H2O)].3H2O RC3,
      2[Gd( m-CPA)3(H2O)].3H2O RC4, and [Ce2( m-CPA)6(H2O)3].2H2O RC5. An in vitro cell
      study revealed that all RCs exhibited certain anticancer activities. RC2, in
      particular, showed the strongest cytotoxicity against HepG2 cells. The enhanced
      cell permeability and drug retention considerably improved the cytotoxicity of
      all SiO2@RC2-gal relative to that of RC2. The selective uptake of the beta-d
      galactose-conjugated nanospheres by HepG2 cells through mechanisms mediated by
      cell surface receptors resulted in fewer side effects on extrahepatic tissues.
      Our contribution provides a novel design concept of a target SiO2@RCs-gal
      nanocarrier for delivering affordable antitumor complexes in cancer therapy.

PMID- 30113820
TI  - Impact of Chemoeffectors on Bacterial Motility, Transport, and Contaminant
      Degradation in Sand-Filled Percolation Columns.
AB  - Chemoeffector-mediated bacterial motility and tactic swimming are major drivers
      for contaminant accessibility and biodegradation at submillimeter scales. In sand
      filled percolated columns we tested how and to what degree chemoeffectors
      influenced bacterial transport and thereby promoted accessibility and degradation
      of distantly located 14C-naphthalene (NAH) at the centimeter scale. Sunflower
      root exudates and silver nanoparticles (AgNPs) were used as chemoeffectors to
      stimulate opposing effects of motility and tactic swimming of NAH-degrading
      Pseudomonas putida G7. Sunflower exudates prompted smooth bacterial movement and
      positive taxis, while AgNPs induced tortuous movement and repellent responses.
      Compared to chemoeffector-free controls exudates reduced deposition and
      stimulated bacterial transport during percolation experiments. AgNPs, however,
      provoked bacterial deposition and concomitant saturation of the collector
      surfaces (filter blocking) that led to progressively increased percolation of
      cells. Despite mechanistic differences, both motility patterns supported
      bacterial transport and promoted mineralization rates of NAH desorbing from a
      source placed at the column outlet. Observed mineralization rates in the presence
      of the chemoeffectors were 5-fold higher than those in their absence and similar
      to NAH-mineralization in well-stirred batch assays. Our results indicate that
      chemically mediated, small-scale bacterial motility patterns may become relevant
      for long-distance bacterial transport and the biodegradation of patchy
      contaminants at higher scales, respectively.

PMID- 30113821
TI  - NL2+ Systems as New-Generation Phase-Transfer Catalysts.
AB  - Phase-transfer catalysts (PTCs), currently, are one of the most important tools
      of chemists for performing organic reactions. PTCs accelerate several types of
      reactions in biphasic systems, giving excellent yields of the desired product.
      Most of the PTCs belong to the general formula NR4+X-. In the recent past,
      several compounds possessing a novel scaffold with the general formula NL2+X-
      have been reported as PTCs. In the NL2+ species, a nitrogen atom with a formal
      positive charge accepts electron density from electron-donating ligands.
      Electronic structure studies reported in the literature confirmed the possibility
      of L -> N coordination (donor-acceptor) interactions in these species, and thus,
      this class of compounds are known as divalent NI compounds. These species are
      reported to exhibit better catalytic potential in comparison to the traditional
      NR4+ systems. Some of the NL2+ systems are found to be useful in asymmetric phase
      transfer catalysis. Thus, these systems offer extensive opportunities for
      exploring the catalytic properties and novel mechanistic aspects associated with
      their unique electronic structure. In this paper, the synthesis, electronic, and
      structural properties and the applications in catalysis of the NL2+-based PTCs
      are reviewed with their bright future scope in catalytic organic chemistry.

PMID- 30113822
TI  - Time-Resolved Photoluminescence Microscopy Combined with X-ray Analyses and Raman
      Spectroscopy Sheds Light on the Imperfect Synthesis of Historical Cadmium
      Pigments.
AB  - Recent studies have shown that modern pigments produced after the Second
      Industrial Revolution are complex systems characterized by a high level of
      heterogeneities. Therefore, it is fundamental to adopt a multianalytical approach
      and highly sensitive methods to characterize the impurities present within
      pigments. In this work we propose time-resolved and spectrally resolved
      photoluminescence (PL) microscopy for the mapping of luminescent crystal defects
      and impurities in historical cadmium-based pigments. PL analysis is complemented
      by X-ray diffraction, X-ray fluorescence and Raman spectroscopies, and by
      scanning electron microscopy to determine the chemical composition and crystal
      structure of samples. The study highlights the heterogeneous and complex nature
      of historical samples that can be associated with the imperfect manufacturing
      processes tested during the period between the 1850s and 1950s. The results also
      allow us to speculate on a range of synthesis processes. Since it is recognized
      that the stability of paints can be related to pigments synthesis, this research
      paves the way to a wider study on the relationship between synthesis methods and
      deterioration of cadmium pigments and paints. This rapid and immediate approach
      using PL can be applied to other semiconductor pigments and real case studies.

PMID- 30113823
TI  - Innovative Approaches for Estimating the Levels of Tobacco-Specific Nitrosamines
      in Cured Tobacco Samples.
AB  - Tobacco-specific nitrosamines (TSNAs), mainly the 4-(methylnitrosamino)-1-(3
      pyridyl)-1-butanone (NNK), are known carcinogens. Part of the NNK found in smoke
      is provided from matrix-bound NNK, and its determination is extremely relevant.
      However, the reference extraction procedure of matrix-bound NNK is time-consuming
      and labor-intensive and has a limited analytical capacity. Three different
      methodologies were proposed to predict matrix-bound NNK: simple linear regression
      (LR) with soluble NNK; multiple linear regression (MLR) considering soluble NNK
      and characteristic parameters of the samples; and orthogonal partial least
      squares (O-PLS) regression using high-throughput screening by flow injection
      analysis coupled to high-resolution mass spectrometry (HTS-FIA-HRMS) data. Simple
      linear regression showed a high influence of matrix and leaf origin. Although an
      existing linearity trend has been observed ( R2 = 0.62) for the global model,
      higher correlation values were achieved for matrix and country segregation
      models. Multiple linear regression predicted matrix-bound NNK with more
      satisfactory efficiency than simple linear regression models. The coefficients of
      determination were 0.87 and 0.94 for flue-cured Virginia and air-cured Burley,
      respectively. However, this method has a limited application, since previous
      information about the sample is required. The proposed method based on HTS-FIA
      HRMS and O-PLS has shown the most suitable performance in the prediction of
      matrix-bound NNK, with errors comparable to the reference method, and a higher
      throughput. In addition, this approach allows to determine other soluble
      nitrosamines, namely N'-nitrosoanatabine, N'-nitrosoanabasine, and N
      nitrosonornicotine, with relative percentage errors between 5.25 and 11.98%.
      Therefore, the third approach is the best method for a large number of cured
      tobacco for accuracy in determination of TSNAs.

PMID- 30113824
TI  - Computational Optics Enables Breast Cancer Profiling in Point-of-Care Settings.
AB  - The global burden of cancer, severe diagnostic bottlenecks in underserved
      regions, and underfunded health care systems are fueling the need for
      inexpensive, rapid, and treatment-informative diagnostics. On the basis of
      advances in computational optics and deep learning, we have developed a low-cost
      digital system, termed AIDA (artificial intelligence diffraction analysis), for
      breast cancer diagnosis of fine needle aspirates. Here, we show high accuracy
      (>90%) in (i) recognizing cells directly from diffraction patterns and (ii)
      classifying breast cancer types using deep-learning-based analysis of sample
      aspirates. The image algorithm is fast, enabling cellular analyses at high
      throughput (~3 s per 1000 cells), and the unsupervised processing allows use by
      lower skill health care workers. AIDA can perform quantitative molecular
      profiling on individual cells, revealing intratumor molecular heterogeneity, and
      has the potential to improve cancer diagnosis and treatment. The system could be
      further developed for other cancers and thus find widespread use in global
      health.

PMID- 30113825
TI  - Kinetic Study of Chiral Intermolecular Interactions by Moment Analysis Based on
      Affinity Capillary Electrophoresis.
AB  - Capillary electrophoresis is a method for analyzing intermolecular interactions
      that does not require immobilization of molecules to a solid surface or
      introduction of a luminescent moiety. Recently, an advanced method, moment
      analysis based on affinity capillary electrophoresis (MA-ACE), was developed.
      This method can determine not only the equilibrium constant but also the rate
      constants of an intermolecular interaction. Through MA-ACE, it became possible to
      theoretically predict an increase in the variance of an observed peak caused by
      intermolecular interaction. In this study, we confirm the prediction and
      determine the kinetic constants by using MA-ACE to analyze an intermolecular
      interaction between cyclodextrin and phenoxypropionic acid. A numerical
      calculation is performed to confirm that the derived rate constants by MA-ACE are
      appropriate.

PMID- 30113826
TI  - Gas/Particle Partitioning Constants of Nicotine, Selected Toxicants, and Flavor
      Chemicals in Solutions of 50/50 Propylene Glycol/Glycerol As Used in Electronic
      Cigarettes.
AB  - For an electronic cigarette (e-cigarette) aerosol with known total particulate
      matter concentration (TPM, MUg/m3), predictions of the fractions of some compound
      i in the gas and particle phases ( fg, i and fp, i) at equilibrium can be made
      based on Kp, i (m3/MUg), the compound-dependent gas/particle partitioning
      equilibrium constant. fg, i and fp, i affect the modes and locations of
      deposition in the respiratory tract. Kp, i depends inversely on (1) the pure
      compound liquid vapor pressure ( pL, io), (2) mole fraction activity coefficient
      (zeta i) in the absorbing liquid, and (3) mean molecular weight of the absorbing
      liquid (MW). Kp, i values were measured at 20  degrees C for 32 compounds as
      spiked into simulated e-cigarette liquids prepared as 50/50 mixtures (by weight)
      of propylene glycol (PG) and glycerol (GL). Kp, i values at 37  degrees C were
      estimated. The 32 compounds were nicotine (in free-base form), seven toxicants
      (propanal, acetone, hydroxyacetone, benzene, toluene, p-xylene, and
      ethylbenzene), and 24 flavor chemicals (2,3-pentanedione ("acetyl propionyl"),
      isobutyl acetate, ethyl butyrate, butyl butyrate, isoamyl acetate, 2,3
      dimethylpyrazine, 3-methyl-1-butanol, limonene, 2,3,5-trimethylpyrazine, p
      cymene, benzaldehyde, ( Z)-3-hexen-1-ol, menthol, 2-acetylpyrrole, benzyl
      alcohol, methyl salicylate, cinnamaldehyde, methyl anthranilate, (+)
      aromadendrene, cinnamyl alcohol, methyl cinnamate, maltol, ethyl maltol, and
      coumarin). The measured log Kp, i values were found to be generally correlated
      with literature values of log pL, io; the scatter is caused by variation in zeta
      i between ~1 and ~1000. Kp measurements were attempted, but values were not
      reported for acetaldehyde, 2,3-butanedione (diacetyl), vanillin, and ethyl
      vanillin. Acetaldehyde was found to form significant amounts of its cyclic trimer
      and cyclic tetramer; for diacetyl, the evidence suggested significant amounts of
      reaction products, possibly hemiketals and ketals with PG/GL, and for vanillin
      and ethyl vanillin, the Kp values are large and accordingly more difficult to
      measure. fg values are calculated using a range of Kp and TPM values.

PMID- 30113827
TI  - Effect of Microplastic Amendment to Food on Diet Assimilation Efficiencies of
      PCBs by Fish.
AB  - Diet assimilation efficiencies (AEs) of polychlorinated biphenyls (PCBs) absorbed
      to microplastics and food were determined in goldfish ( Carassius auratus).
      Microplastics were spiked with 14 environmentally rare PCBs and incorporated into
      fish pellets previously spiked with a technical PCB mixture (Aroclor 1254). Five
      diet treatments were created having microplastic contents of 0, 5, 10, 15, 20,
      and 25% and fed to fish within 24 h of the diet creation. Fish from each
      treatment were fed a microplastic amended food pellet and PCB AEs were determined
      by mass balance. Microplastic-associated PCBs had lower AEs (geomean 13.36%)
      compared to food matrix-associated PCBs (geomean 51.64%). There were interactions
      between PCB AEs and the microplastic content of the diet. PCBs affiliated with
      microplastics became more bioavailable with increasing microplastic content of
      food while food matrix-associated PCB bioavailability declined when microplastic
      contents exceeded 5%. Despite controlling for microplastic-food contact time,
      there was some evidence for redistribution of lower KOW food matrix-associated
      PCBs onto microplastics causing a decrease in their AE relative to nonplastic and
      low plastic containing diets. The low bioavailability of microplastic-associated
      PCBs observed in the present study provides further support to indicate that
      microplastics are unlikely to increase POPs bioaccumulation by fish in aquatic
      systems.

PMID- 30113828
TI  - Toward a Predictive Understanding of Phosphine-Catalyzed [3 + 2] Annulation of
      Allenoates with Acrylate or Imine.
AB  - Both theoretical and experimental studies were performed to explore the
      mechanism, regioselectivity, and enantioselectivity of phosphine-catalyzed [3 +
      2] annulation between allenoates and acrylate or imine. Using density functional
      theory computations, we predicted that the enantioselective determining step is
      the nucleophilic addition of acrylate or imine to the catalyst-activated
      allenoate. In the key step, we proposed two hydrogen bonding interaction models
      (intermolecular H-bond model and intramolecular H-bond model). For acrylate
      substrates, the reaction proceeds via the intramolecular H-bond model and the
      strong noncovalent interactions between the 2-naphthyl ester moiety lead to the
      re-face attack pathway being more favorable. For imine substrates, the
      intermolecular H-bond model operates. In the annulation process, the bulky n
      propyl oriented toward a crowded, sterically demanding environment plays a
      significant role in asymmetric induction. The theoretical calculation results
      agreed with experimental observations, and these results provide valuable insight
      into catalyst design and understanding of mechanisms of related reactions.

PMID- 30113830
TI  - Tuning the Spin, Aromaticity, and Quantum Tunneling in Computationally Designed
      Fulvalenes.
AB  - Pentafulvalene is a symmetrical unsaturated hydrocarbon built from two five
      membered rings connected by an exocyclic double bond, where each ring is one
      electron short of being a 6pi-electron aromatic system. Here, we show
      computationally that by selectively introducing electron withdrawing and donating
      substituents, we can design pentafulvalene derivatives that exhibit tunable
      aromaticity properties. Pentafulvalene can be shaped into a species with
      connected aromatic-antiaromatic rings, which can also achieve pi-bond shifting by
      carbon tunneling. We propose an NMR technique that can experimentally prove such
      tunneling mechanism. In addition, we devised a doubly aromatic fulvalene
      involving both Huckel and Baird aromaticities. These results can open
      possibilities to create novel molecules in terms of spin state, aromaticity, and
      reactivity by quantum tunneling.

PMID- 30113829
TI  - Complex Topologies from Simple Building Blocks: Uranium(IV) Thiophosphates.
AB  - Six new uranium thiophosphates, Cs5Na6[U(PS4)4](PS4) (1), Rb5Na3[U(PS4)4] (2),
      CsNa[U(PS4)2] (3), Cs1.67Na0.52I0.19[U(PS4)2] (4), Cs1.033Na1.343I0.376[U(PS4)2]
      (5), and Rb1.35Na0.93I0.28[U(PS4)2] (6), were obtained from halide flux reactions
      and characterized using single-crystal X-ray diffraction. The structures of these
      compounds consist of a pseudotetrahedral uranium unit that in combination with a
      set of PS4 group coordination modes can result in an isolated [U(PS4)4]8- unit, a
      [U(PS4)2]2- chain, or a [U(PS4)2]2- slab. Optical and magnetic properties of 3
      and 4 were collected. Both compounds exhibit paramagnetic behavior, and
      CsNa[U(PS4)2] (3) exhibits a magnetic transition at 200-225 K between two
      paramagnetic states that both have similar effective magnetic moments of 4.13 and
      4.19 MUB/formula unit, and strong antiferromagnetic interactions with theta = 
      183 and -172 K, for the high- and low-temperature states, respectively.

PMID- 30113831
TI  - Come Together: Molecular Details into the Synergistic Effects of Polymer
      Surfactant Adsorption at the Oil/Water Interface.
AB  - The synergistic adsorption of polymers with surfactants at the oil/water
      interface has applications that range from oil remediation to targeted drug
      delivery. However, the inherent inaccessibility of the buried oil/water interface
      has challenged the development of a molecular-level understanding of the
      structure-function relationship of these systems. This study uses vibrational sum
      frequency spectroscopy to examine the molecular structure, orientation, and
      electrostatic effects of synergistic adsorption of the surfactant cetrimonium
      bromide (CTAB) and polymer poly(acrylic acid) (PAA) at a planar oil/water
      interface. Results demonstrate that coadsorption leads to a high degree of
      interfacial ordering of both the polymer and the surfactant and a subsequent
      alteration of the interfacial water bonding and orientation. Complementary zeta
      potential measurements provide further information about how surface partitioning
      of a charged polymer and a surfactant relates to their aggregation behavior in a
      bulk solution. With the CTAB concentration fixed but the PAA concentration
      variable, hydrophobic interactions result in a modest synergic coadsorption when
      CTAB is in excess. However, when the PAA carboxylate monomer concentration
      approaches that of CTAB, the electrostatic interactions between the components
      change the structure and increase the amount of adsorbed PAA until the
      interfacial charge is neutralized. This work reveals that the synergic adsorption
      behavior of this model polyacid/surfactant system arises from a combination of
      concentration-dependent hydrophobic and electrostatic forces working in tandem.

PMID- 30113832
TI  - Mass Spectrometric Study on the Combustion of Tetramethylsilane and the Formation
      of Silicon Oxide Clusters in Premixed Laminar Low-Pressure Synthesis Flames.
AB  - This work investigates the decomposition of tetramethylsilane and the formation
      of silicon oxide clusters in a laminar premixed low-pressure hydrogen flame using
      molecular-beam mass spectrometry (MBMS). A comprehensive list of the species that
      exist in the gas phase was compiled and spatially resolved mole fraction profiles
      of species in the flame were obtained. Quantitative data in dependence of height
      above the burner were obtained for all major species and intermediates. The MBMS
      detection technique allowed to monitor Si-C-O-H, and Si-O-H-containing compounds
      as well as C1-C2 species. The measured data show that the reaction of
      tetramethylsilane is initiated by H-abstraction from a methyl group and
      subsequent formation of oxygenated species. The measurements suggest that
      combustion of tetramethylsilane in a hydrogen flame proceeds mainly by a stepwise
      substitution of the methyl ligands by hydroxyl groups. Molecular and radical
      intermediates like Si(CH3)2OH, Si(OH)3, and Si(OH)4 are formed in the reaction
      zone. Significant amounts of Si(OH)4 are present at large distances above the
      burner. A repetitive growth pattern suggests that the monomer Si(OH)4 is a likely
      species initiating the formation and growth of larger silicon oxide clusters,
      e.g., Si4O10H4, Si5O12H4, and Si6O14H4, that can form nanoparticles in subsequent
      reactions.

PMID- 30113833
TI  - A Flexible Metal-Organic Framework with 4-Connected Zr6 Nodes.
AB  - Zr-based metal-organic frameworks (MOFs) have been known for their excellent
      stability; however, due to the high connectivity of the Zr6 nodes, it is
      challenging to introduce flexibility into Zr-MOFs. Here we present a flexible Zr
      MOF named NU-1400 comprising 4-connected Zr6 nodes and tetratopic linkers. It
      exhibits guest-dependent structural flexibility with up to 48% contraction in the
      unit cell volume as evidenced by single-crystal X-ray diffraction studies. The
      expanded or contracted conformations of NU-1400 showed drastically different
      reactivity toward the hydrolysis of a nerve agent simulant owing to the size
      selective effect toward the reactant.

PMID- 30113834
TI  - Metal-Organic Frameworks Mediate Cu Coordination for Selective CO2
      Electroreduction.
AB  - The electrochemical carbon dioxide reduction reaction (CO2RR) produces diverse
      chemical species. Cu clusters with a judiciously controlled surface coordination
      number (CN) provide active sites that simultaneously optimize selectivity,
      activity, and efficiency for CO2RR. Here we report a strategy involving metal
      organic framework (MOF)-regulated Cu cluster formation that shifts CO2
      electroreduction toward multiple-carbon product generation. Specifically, we
      promoted undercoordinated sites during the formation of Cu clusters by
      controlling the structure of the Cu dimer, the precursor for Cu clusters. We
      distorted the symmetric paddle-wheel Cu dimer secondary building block of HKUST-1
      to an asymmetric motif by separating adjacent benzene tricarboxylate moieties
      using thermal treatment. By varying materials processing conditions, we modulated
      the asymmetric local atomic structure, oxidation state and bonding strain of Cu
      dimers. Using electron paramagnetic resonance (EPR) and in situ X-ray absorption
      spectroscopy (XAS) experiments, we observed the formation of Cu clusters with low
      CN from distorted Cu dimers in HKUST-1 during CO2 electroreduction. These
      exhibited 45% C2H4 faradaic efficiency (FE), a record for MOF-derived Cu cluster
      catalysts. A structure-activity relationship was established wherein the tuning
      of the Cu-Cu CN in Cu clusters determines the CO2RR selectivity.

PMID- 30113835
TI  - Thiols as Hydrogen Bond Acceptors and Donors: Spectroscopy of 2-Phenylethanethiol
      Complexes.
AB  - Evidence and understanding of sulfur-centered hydrogen bonding, especially where
      the donor is a thiol, lags far behind that for conventional OH interactions. To
      help address this deficiency, conformer specific IR spectra of 2
      phenylethanethiol (PET) and associated 1:1 solvent complexes have been measured
      in SH, OH, and CH stretch regions using resonant-two-photon-ionization (R2PI) and
      IR-UV ion dip spectroscopic techniques. The aromatic and aliphatic CH stretch
      regions show signature differences between anti and gauche conformers. Supported
      by ab initio calculations, a PET-water cluster with an OH...S arrangement and a
      PET-diethyl ether cluster expressing an SH...O interaction were identified. The
      SH stretch band of the SH...O complex is red-shifted and undergoes significant
      intensity enhancement compared to the bare molecule, which is characteristic of
      hydrogen bonding. These findings offer insight into the nature of the thiol
      functional group as a potential hydrogen bond donor and acceptor.

PMID- 30113836
TI  - Chemo-enzymatic Total Syntheses of Jorunnamycin A, Saframycin A, and N-Fmoc
      Saframycin Y3.
AB  - The antitumor tetrahydroisoquinoline (THIQ) alkaloids share a common pentacyclic
      scaffold that is biosynthesized by nonribosomal peptide synthetases involving
      unique enzymatic Pictet-Spengler cyclizations. Herein we report concise and
      divergent chemo-enzymatic total syntheses of THIQ alkaloids by merging precise
      chemical synthesis with in vitro engineered biosynthesis. A recombinant enzyme
      SfmC responsible for the biosynthesis of saframycin A was adapted for the
      assembly of these natural products and their derivatives, by optimizing designer
      substrates compatible with SfmC through chemical synthesis. The appropriately
      functionalized pentacyclic skeleton were efficiently synthesized by streamlining
      the linkage between SfmC-catalyzed multistep enzymatic conversions and chemical
      manipulations of the intermediates to install aminonitrile and N-methyl groups.
      This approach allowed rapid access to the elaborated pentacyclic skeleton in a
      single day starting from two simple synthetic substrates without isolation of the
      intermediates. Further functional group manipulations allowed operationally
      simple and expeditious syntheses of jorunnamycin A, saframycin A, and N-Fmoc
      saframycin Y3 that could be versatile and common precursors for the artificial
      production of other antitumor THIQ alkaloids and their variants.

PMID- 30113837
TI  - N-Heterocyclic Carbene-Catalyzed Formal Conjugate Hydroacylation: An Atom
      Economic Synthesis of 1 H-Indol-3-yl Esters.
AB  - An atom-economic synthesis of useful 1 H-indol-3-yl esters has been demonstrated
      by an N-heterocyclic carbene (NHC)-catalyzed formal conjugate hydroacylation of 2
      phenyl-indol-3-ones with readily accessible aldehydes. This reaction involves a
      reductive hydride transfer process that was rarely investigated in the field of
      NHC catalysis. In this process, the hydrogen from the aldehydes was formally
      transferred to a heteroatom with NHC catalysis for the first time.

PMID- 30113838
TI  - NHC Ligated Group 11 Metal-Arylthiolates Containing an Azide Functionality
      Amenable to "Click" Reaction Chemistry.
AB  - The reaction of N-heterocyclic carbene (NHC) Group 11 metal complexes, [(NHC)M-X]
      (X = chloride, acetate), with the new azide-modified arylthiol 1-HSCH2-2,5-Me2-4
      N3CH2-C6H2, 1 (for M = Au; X = Cl), or 1-Me3SiSCH2-2,5-Me2-4-N3CH2-C6H2, 2 (for M
      = Cu, X = Cl; M = Ag, X = OAc), affords the "clickable" NHC-metal thiolates [(
      iPr2-bimy)Au-(1-SCH2-2,5-Me2-4-N3CH2-C6H2)], 5; [(IPr)Au-(1-SCH2-2,5-Me2-4-N3CH2
      C6H2)], 6; [(IPr)Ag-(1-SCH2-2,5-Me2-4-N3CH2-C6H2)], 7; and [(IPr)Cu-(1-SCH2-2,5
      Me2-4-N3CH2-C6H2)], 8 ( iPr2-bimy = 1,3-di-isopropylbenzimidazol-2-ylidene, IPr =
      1,3-bis(2,6-di-iso-propylphenyl)imidazol-2-ylidene). Single-crystal X-ray
      analysis of all metal complexes show that they are two-coordinate, nearly linear,
      with a terminally bonded thiolate ligand possessing an accessible azide (-N3)
      moiety. The strain-promoted alkyne-azide cycloaddition (SPAAC) reaction of
      complex 6 with bicyclo[6.1.0]non-4-yn-9-ylmethanol (BCN-OH) and
      dibenzocyclooctyne-amine (DBCO-NH2) illustrated the reactivity of the azide
      moiety toward strain-promoted cycloaddition. The rate of the SPAAC reaction
      between complex 6 and BCN-OH was determined via 1H NMR spectroscopy under second
      order conditions, and was compared to that of BCN-OH with PhCH2N3.

PMID- 30113839
TI  - Synthetic Routes to a Triazole and Tetrazole with Trinitroalkyl Substitution at
      Nitrogen.
AB  - Two N-substituted trinitroalkyl azoles, one triazole, and one tetrazole were
      synthesized and isolated via efficient cyclization reactions. Both materials were
      thoroughly characterized, and their structures were confirmed by X-ray
      diffraction. The formation of the N-trinitroethyl substituted triazole proceeds
      unexpectedly via nitrosation of an N-substituted diaminomaleonitrile initially
      with HNO3 and subsequently confirmed with HNO2. The N-trinitropropyl substituted
      tetrazole was prepared via a standard cyclization route from
      trinitropropylammonium chloride with orthoformate and azide.

PMID- 30113840
TI  - Revisiting the Dependence of Cu K-Edge X-ray Absorption Spectra on Oxidation
      State and Coordination Environment.
AB  - X-ray absorption spectroscopy (XAS) at the Cu K-edge is an important tool for
      probing the properties of copper centers in transition-metal chemistry and
      catalysis. However, the interpretation of experimental XAS spectra requires a
      detailed understanding of the dependence of spectroscopic features on the local
      geometric and electronic structure, which can be established by theoretical X-ray
      spectroscopy. Here, we present a systematic computational study of the Cu K-edge
      XAS spectra of selected Cu complexes based on time-dependent density-functional
      theory in combination with a molecular orbital analysis of the relevant
      transitions. For a series of Cu ammine model complexes as well as a comprehensive
      test set of 12 Cu(I) and 5 Cu(II) complexes, we revisit the dependence of the pre
      edge region in Cu K-edge XAS spectra on oxidation state and coordination
      geometry. While our calculations confirm earlier experimental assignments, we can
      also reveal additional signatures of the ligand orbitals and identify the
      underlying orbital interactions. The comprehensive picture revealed by this study
      will provide a reliable basis for the interpretation of in situ Cu K-edge XAS
      spectra of catalytic intermediates.

PMID- 30113841
TI  - Pesticide Detox by Design.
AB  - Detoxification (detox) plays a major role in pesticide action and resistance. The
      mechanisms involved are sometimes part of the discovery and development process
      in seeking new biochemical targets and metabolic pathways. Genetically modified
      and chemical-safener-modified crops are a marked exception and often involve
      herbicide detox by design to achieve the required crop tolerance. This
      perspective evaluates the role of detox by design or chance and target-site-based
      selectivity in insecticide, herbicide, and fungicide action and human health and
      environmental effects.

PMID- 30113843
TI  - Divergent Diels-Alder Reactions in the Biosynthesis and Synthesis of Endiandric
      Type Tetracycles: A Computational Study.
AB  - Endiandric acids and related polyketide natural products arise from polyene
      precursors and occur naturally as fused and bridged tetracycles. In some cases,
      the intramolecular Diels-Alder reactions that produce fused and bridged
      tetracycles result from a diene tether that may act as either a 4pi or 2pi
      component in the cycloaddition. To examine the preference for fused or bridged
      products, we applied density functional theory (using the M06-2X and B3LYP
      functionals) to reactants with various substituents for both fused and bridged
      transition states. Fused products were generally preferred except when disfavored
      by extreme steric hindrance (e.g., a tert-butyl group). These computational
      results are consistent with experimental data and suggest the existence of as-yet
      undiscovered natural products.

PMID- 30113842
TI  - Assimilating Radial Distribution Functions To Build Water Models with Improved
      Structural Properties.
AB  - The structural properties of three- and four-site water models are improved by
      extending the ForceBalance parametrization code to include a new methodology
      allowing for the targeting of any radial distribution function (RDF) during the
      parametrization of a force field. The mean squared difference (MSD) between the
      experimental and simulated RDFs contributes to an objective function, allowing
      for the systematic optimization of force field parameters to reach closer overall
      agreement with experiment. RDF fitting is applied to develop modified versions of
      the TIP3P and TIP4P/2005 water models in which the Lennard-Jones potential is
      replaced by a Buckingham potential. The optimized TIP3P-Buckingham and TIP4P
      Buckingham potentials feature 93 and 98% lower MSDs in the OO RDF compared to the
      TIP3P and TIP4P/2005 models respectively, with marked decreases in the height of
      the first peak. Additionally, these Buckingham models predict the entropy of
      water more accurately, reducing the error in the entropy of TIP3P from 11 to 3%
      and the error in the entropy of TIP4P/2005 from 11 to 2%. These new Buckingham
      models have improved predictive power for many nonfitted properties particularly
      in the case of TIP3P. Our work directly demonstrates how the Buckingham potential
      can improve the description of water's structural properties beyond the Lennard
      Jones potential. Moreover, adding a Buckingham potential is a favorable
      alternative to adding interaction sites in terms of computational speed on modern
      GPU hardware.

PMID- 30113845
TI  - Biophysical Mechanisms of Membrane-Thickness-Dependent MscL Gating: An All-Atom
      Molecular Dynamics Study.
AB  - The bacterial mechanosensitive channel, MscL, is activated by membrane tension,
      acting as a safety valve to prevent cell lysis against hypotonic challenge. It
      has been established that its activation threshold decreases with membrane
      thickness, while the underlying mechanism remains to be solved. We performed all
      atom molecular dynamics (MD) simulations for the initial opening process of MscL
      embedded in four different types of lipid bilayers with different thicknesses:
      1,2-dilauroyl- sn-glycero-3-phosphocholine (DLPC)), 1,2-dimyristoyl-glycero-3
      phosphorylcholine (DMPC), 1,2-dipalmitoyl- sn-glycero-3-phosphocholine (DPPC),
      and 1,2-distearoyl- sn-glycero-3-phosphocholine (DSPC). In response to membrane
      stretching, channel opening occurred only in the thinner membranes (DLPC and
      DMPC) in a thickness-dependent way. We found that the MscL opening was governed
      by the rate and degree of membrane thinning and that the channel opening was
      tightly associated with the tilting of transmembrane (TM) helices of MscL toward
      the membrane plane. Upon membrane stretching, the order parameter of acyl chains
      of thinner membranes (DLPC and DMPC) became smaller, whereas other thicker
      membranes (DPPC and DSPC) showed interdigitation with little changes in the order
      parameter. The decreased order parameter contributed much more to membrane
      thinning than did interdigitation. We conclude that the membrane-thickness
      dependent MscL opening mainly arises from structural changes in MscL to match the
      altered membrane thickness by stretching.

PMID- 30113844
TI  - Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases:
      Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol
      4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF
      06700841).
AB  - Cytokine signaling is an important characteristic of autoimmune diseases. Many
      pro-inflammatory cytokines signal through the Janus kinase (JAK)/Signal
      transducer and activator of transcription (STAT) pathway. JAK1 is important for
      the gamma-common chain cytokines, interleukin (IL)-6, and type-I interferon (IFN)
      family, while TYK2 in addition to type-I IFN signaling also plays a role in IL-23
      and IL-12 signaling. Intervention with monoclonal antibodies (mAbs) or JAK1
      inhibitors has demonstrated efficacy in Phase III psoriasis, psoriatic arthritis,
      inflammatory bowel disease, and rheumatoid arthritis studies, leading to multiple
      drug approvals. We hypothesized that a dual JAK1/TYK2 inhibitor will provide
      additional efficacy, while managing risk by optimizing selectivity against JAK2
      driven hematopoietic changes. Our program began with a conformationally
      constrained piperazinyl-pyrimidine Type 1 ATP site inhibitor, subsequent work led
      to the discovery of PF-06700841 (compound 23), which is in Phase II clinical
      development (NCT02969018, NCT02958865, NCT03395184, and NCT02974868).

PMID- 30113846
TI  - One-Dimensional Confinement Inhibits Water Dissociation in Carbon Nanotubes.
AB  - The effect of nanoconfinement on the self-dissociation of water constitutes an
      open problem whose elucidation poses a serious challenge to experiments and
      simulations alike. In slit pores of width ~1 nm, recent first-principles
      calculations have predicted that the dissociation constant of H2O increases by
      almost 2 orders of magnitude [ Munoz-Santiburcio and Marx, Phys. Rev. Lett. 2017
      , 119 , 056002 ]. In the present study, quantum mechanics-molecular mechanics
      simulations are employed to compute the dissociation free-energy profile of water
      in a (6,6) carbon nanotube. According to our results, the equilibrium constant Kw
      drops by 3 orders of magnitude with respect to the bulk phase value, at variance
      with the trend predicted for confinement in two dimensions. The higher barrier to
      dissociation can be ascribed to the undercoordination of the hydroxide and
      hydronium ions in the nanotube and underscores that chemical reactivity does not
      exhibit a monotonic behavior with respect to pore size but may vary substantially
      with the characteristic length scale and dimensionality of the confining media.

PMID- 30113847
TI  - Correction to Brightly Luminescent and Color-Tunable Formamidinium Lead Halide
      Perovskite FAPbX3 (X = Cl, Br, I) Colloidal Nanocrystals.

PMID- 30113848
TI  - Copper-Catalyzed Propargylic Reduction with Diisobutylaluminum Hydride.
AB  - A mild and efficient method for the synthesis of allenes through selective copper
      catalyzed hydride addition to propargylic chlorides using commercially available
      diisobutylaluminum hydride has been developed. This transformation, which is
      promoted by a readily accessible N-heterocyclic carbene-copper complex, provides
      a wide range of new and versatile functionalized allenes in good to excellent
      yields with high regio- and stereoselectivities.

PMID- 30113849
TI  - Synephrine Hydrochloride Suppresses Esophageal Cancer Tumor Growth and Metastatic
      Potential through Inhibition of Galectin-3-AKT/ERK Signaling.
AB  - A library consisting of 429 food-source compounds was used to screen the natural
      products with anticancer properties in esophageal squamous cell carcinoma (ESCC).
      We demonstrated for the first time that synephrine, an active compound isolated
      from leaves of citrus trees, markedly suppressed cell proliferation (inhibition
      rate with 20 MUM synephrine at day 5:71.1 +/- 5.8% and 75.7 +/- 6.2% for KYSE30
      and KYSE270, respectively) and colony formation (inhibition rate with 10 MUM
      synephrine: 86.5 +/- 5.9% and 82.3 +/- 4.5% for KYSE30 and KYSE270,
      respectively), as well as migration (inhibition rate with 10 MUM synephrine: 76.9
      +/- 4.4% and 62.2 +/- 5.8% for KYSE30 and KYSE270, respectively) and invasion
      abilities (inhibition rate with 10 MUM synephrine: 73.3 +/- 7.5% and 75.3 +/-
      3.4% for KYSE30 and KYSE270, respectively) of ESCC cells in a dose-dependent
      manner, without significant toxic effect on normal esophageal epithelial cells.
      Mechanistically, quantitative proteomics and bioinformatics analyses were
      performed to explore the synephrine-regulated proteins. Western blot and qRT-PCR
      data indicated that synephrine may downregulate Galectin-3 to inactivate AKT and
      ERK pathways. In addition, we found that the sensitivity of ESCC to fluorouracil
      (5-FU) could be enhanced by synephrine. Furthermore, in vivo experiments showed
      that synephrine had significant antitumor effect on ESCC tumor xenografts in nude
      mice (inhibition rate with 20 mg/kg synephrine is 61.3 +/- 20.5%) without
      observed side effects on the animals. Taken together, synephrine, a food-source
      natural product, may be a potential therapeutic strategy in ESCC.

PMID- 30113850
TI  - Anisotropic Reactivity of CaAg under Ethylene Epoxidation Conditions.
AB  - The chemical behavior of CaAg as catalyst for ethylene epoxidation was studied
      using a combination of experimental (X-ray powder diffraction, scanning electron
      microscopy, thermal analysis and infrared spectroscopy), and quantum chemical
      techniques as well as real-space chemical bonding analysis. Under oxidative
      ethylene epoxidation conditions, the CaAg (010) surface possesses an outstanding
      stability during long-term experiments. It is caused by the formation of an
      ordered, stable and dense CaO passivation layer with a small amount of embedded
      Ag atoms. On this way, the (010) surface constitutes a kinetic barrier for
      further incorporation of oxygen into the subsurface region and thereby prevents 
      further oxidative decomposition of CaAg. The calculated adsorption energies of
      the reaction species show strong adsorption of the reaction products that may
      explain the observed low conversion of ethylene toward ethylene oxide using CaAg
      as catalyst.

PMID- 30113851
TI  - Seeing, Targeting and Delivering with Upconverting Nanoparticles.
AB  - Efficient control over drug release is critical to increasing drug efficacy and
      avoiding side effects. An ideal drug delivery system would deliver drugs in the
      right amount, at the right location and at the right time noninvasively. This can
      be achieved using light-triggered delivery: light is noninvasive, spatially
      precise and safe if appropriate wavelengths are chosen. However, the use of light
      controlled delivery systems has been limited to areas that are not too deep
      inside the body because ultraviolet (UV) or visible (Vis) light, the typical
      wavelengths used for photoreactions, have limited penetration and are toxic to
      biological tissues. The advent of upconverting nanoparticles (UCNPs) has made it
      possible to overcome this crucial challenge. UCNPs can convert near-infrared
      (NIR) radiation, which can penetrate deeper inside the body, to shorter
      wavelength NIR, Vis and UV radiation. UCNPs have been used as bright, in situ
      sources of light for on-demand drug release and bioimaging applications. These
      remote-controlled, NIR-triggered drug delivery systems are especially attractive
      in applications where a drug is required at a specific location and time such as
      in anesthetics, postwound healing, cardiothoracic surgery and cancer treatment.
      In this Perspective, we discuss recent progress and challenges as well as propose
      potential solutions and future directions, especially with regard to their
      translation to the clinic.

PMID- 30113852
TI  - Proteomic Analysis of Urine from California Sea Lions ( Zalophus californianus):
      A Resource for Urinary Biomarker Discovery.
AB  - Urinary markers for the assessment of kidney diseases in wild animals are
      limited, in part, due to the lack of urinary proteome data, especially for marine
      mammals. One of the most prevalent kidney diseases in marine mammals is caused by
      Leptospira interrogans, which is the second most common etiology linked to
      stranding of California sea lions ( Zalophus californianus). Urine proteins from
      11 sea lions with leptospirosis kidney disease and eight sea lions without
      leptospirosis or kidney disease were analyzed using shotgun proteomics. In total,
      2694 protein groups were identified, and 316 were differentially abundant between
      groups. Major urine proteins in sea lions were similar to major urine proteins in
      dogs and humans except for the preponderance of resistin, lysozyme C, and PDZ
      domain containing 1, which appear to be over-represented. Previously reported
      urine protein markers of kidney injury in humans and animals were also
      identified. Notably, neutrophil gelatinase-associated lipocalin, osteopontin, and
      epidermal fatty acid binding protein were elevated over 20-fold in the
      leptospirosis-infected sea lions. Consistent with leptospirosis infection in
      rodents, urinary proteins associated with the renin-angiotensin system were
      depressed, including neprilysin. This study represents a foundation from which to
      explore the clinical use of urinary protein markers in California sea lions.

PMID- 30113853
TI  - Burden of Diseases and Injuries in Afghanistan, 1990-2016: Findings From the
      Global Burden of Disease 2016 Study.
AB  - BACKGROUND: Afghanistan is one of the low-income countries in the Eastern
      Mediterranean Region with young population and myriad of healthcare needs. We aim
      to report the burden of diseases and injuries in Afghanistan between 1990 and
      2016. METHODS: We used the Global Burden of Disease (GBD) 2016 study for
      estimates of deaths, disability-adjusted life years (DALYs), years of life lost,
      years of life lived with disability, maternal mortality ratio (MMR), neonatal
      mortality rates (NMRs) and under 5 mortality rates (U5MR) in Afghanistan.
      RESULTS: Total mortality rate, NMR and U5MR have progressively decreased between
      1990 and 2016. Mortality rate was 909.6 per 100000 (95% UI: 800.9-1023.3) and MMR
      was 442.8 (95% UI: 328.3-595.8) per 100000 live births in 2016. Conflict and
      terrorism, ischemic heart disease (IHD) and road injuries were the leading causes
      of DALY among males of all ages in 2016 with 10.9%, 7.8% and 7.6% of total DALYs
      respectively, whereas among females of all ages lower respiratory infections
      (LRIs), IHD and congenital birth defects were the leading causes of DALY with
      8.7%, 7.0% and 6.5% of total DALYs respectively. CONCLUSION: Despite improvements
      in certain health indicators, our study suggests an urgent intervention to
      improve health status of the country. Peace and safety by means of stopping the
      conflict and terrorism are the mainstay of all other health interventions.
      Improving health infrastructures, boosting maternal and child health (MCH),
      battling infectious diseases as well as chronic disease risk factor modification
      programs can help to decrease burden of diseases.

PMID- 30113854
TI  - Prevalence, Awareness, Treatment, Control, and Correlates of Hypertension in the
      Pars Cohort Study.
AB  - BACKGROUND: High blood pressure is an important risk factor for all-cause
      mortality and cardiovascular mortality and morbidity among Iranians. We aimed to
      estimate its prevalence, correlates, and its rate of awareness, treatment, and
      control in South of Iran. METHODS: The Pars Cohort Study (PCS) was launched in a
      district of Fars province. All residents between 40 and 75 years old in the
      district were recruited from 2012 to 2014. Hypertension was defined as either
      systolic/diastolic blood pressure >= 140/90 mm Hg or taking medications. Logistic
      regression was used to identify the correlates of hypertension and awareness and
      its treatment and control. A total of 9264 participants were recruited. Of the
      total participants, 46.2% were men. The mean age was 52.6 years (SD: 9.7).
      RESULTS: Prevalence of hypertension was 26.9%. Of the total 2489 hypertensives,
      49.6% were aware and 55.7% were under treatment. Blood pressure was controlled in
      69.2% of treated hypertensives. In the adjusted model, female sex and history of
      cardiovascular disease (CVD) were positively associated with having hypertension,
      higher awareness, and better treatment and control. Older age, being overweight
      or obese, and having a history of diabetes were also positively associated with
      having hypertension and higher awareness and treatment; however, being overweight
      or obese was associated with poorer hypertension control. Older age and having a
      history of diabetes did not show a statistically significant association with
      control. CONCLUSION: Being underweight and higher physical activity were
      inversely associated with having hypertension but were not associated with
      awareness, treatment, or control. Prevalence of hypertension is high but the
      rates of awareness, treatment, and control are not adequate.

PMID- 30113855
TI  - Predictors of Long-term Major Adverse Cardiac Events Following Percutaneous
      Coronary Intervention in the Elderly.
AB  - BACKGROUND: We aimed to recognize the predictors of long-term major adverse
      cardiac events (MACE) in the elderly candidates for elective percutaneous
      coronary intervention (PCI) at our center. METHODS: In this retrospective cohort
      study, we reviewed the data of the elderly (age >=65 years) candidates for
      elective PCI who met our study criteria, at Tehran heart center between 2004 and
      2013. Demographic, anthropometric, clinical, angiographic, procedural and follow
      up data of the enrolled patients were retrieved from the angiography/PCI databank
      of our center. The study characteristics of the patients with or without MACE
      were compared in a univariable Cox-regression analysis. A multivariable Cox
      regression model was applied using variables selected from the univariable model
      to determine the predictors of MACE. RESULTS: We reviewed the data of 2772
      patients (mean age=70.8+/-4.7 years, male sex=1726 patients [62.3%]) from which
      393 patients (14.4%) developed MACE. In the multivariable regression model,
      female sex was a protective factor for MACE (hazard ratio [HR]=0.701; P=0.001),
      while presence of diabetes mellitus (HR=1.333; P=0.007), family history of
      coronary artery disease (CAD) (HR=1.489; P=0.003) and plain balloon angioplasty
      (HR=1.810; P=0.010) were independent risk factors for MACE. CONCLUSION: PCI is a
      safe and effective method of revascularization in the elderly patients, and some
      clinical and procedural factors can predict MACE in this group of patients.

PMID- 30113856
TI  - Efficacy of Vancomycin on Gram-Positive Bacterial Infection in Elderly Critical
      Patients and Risk Factors Associated With Nephrotoxicity.
AB  - BACKGROUND: Vancomycin is widely used for infections caused by gram-positive
      bacteria, but little attention has been paid to vancomycin in the treatment of
      critically ill patients aged >=80 years. The aim of the current study was to
      investigate the efficacy of vancomycin and risk factors associated with
      nephrotoxicity of vancomycin in elderly critically ill patients. METHODS: A
      retrospective study was performed in a 14-bed medical-surgical geriatric ICU
      between January 2007 and June 2014. The patients (aged >=80 years) were included
      if they received >=4 doses of vancomycin and the therapy duration was >= 2 hours.
      RESULTS: The clinical efficacy was 74.0% (37/50). The 28-day mortality was 26.0%
      (13/50). Of the patients, 24% (12/50) had nephrotoxicity during vancomycin
      treatment period. The clinical efficacy was 60%, 86.7%, 58.3%, and 33.3%, and the
      28-day mortality rate was 20%, 23.3%, 33.3%, and 33.3%, respectively, when the
      trough concentrations were <=10 MUg/mL, 10-15 MUg/mL, 15-20 MUg/mL, and >=20
      MUg/mL. The multivariate logistic regression analysis showed that an Acute
      Physiology and Chronic Health Evaluation (APACHE) II score >=25 points,
      vancomycin trough concentrations >=15 MUg/mL, and the combined use of diuretics
      (furosemide >=40 mg/d) were independent risk factors leading to nephrotoxicity.
      CONCLUSION: We did not find that higher vancomycin trough concentrations lead to
      better clinical outcomes in elderly critically ill patients. Increased vancomycin
      trough concentrations, high APACHE II scores, and the combined use of diuretics
      may increase the risks of nephrotoxicity in elderly critically ill patients.

PMID- 30113857
TI  - Validation of the Iranian/Persian Version of the Perceived Therapeutic Efficacy
      Scale for Type 2 Diabetes.
AB  - BACKGROUND: The theory if self-efficacy is the central concept of social
      cognitive theory with emphasis on the constructs of efficacy expectation, outcome
      expectation. Efficacy expectation is defined as the person's confidence to carry
      out a specific behavior. Outcome expectation is beliefs that carrying out a
      specific behavior will lead to a specific outcome. While the benefit of measuring
      outcome expectations has been established, there has been no large scale within
      the Iranian context. The purpose of this study is to examine the reliability
      validity of the Persian version of the Perceived Therapeutic Efficacy Scale
      (PTES). METHODS: This study was conducted among 160 patients with type 2 diabetes
      mellitus (T2DM) using a self-administered instrument measuring outcome
      expectation. We used a methodological study design to assess the validity and
      reliability of the translated Persian version of the instrument. RESULTS: The
      findings of the present study support the uni-dimensionality of the Persian
      version of the instrument. The 10 items of the scale account for 73.54% of the
      total variance and the un-rotated factor loadings ranged from 0.66 to 0.93.
      Moreover, this study offers support for convergent validity and internal
      consistency of the scale. CONCLUSION: Our study demonstrated good convergent
      validity, factor structure and internal consistency in a sample of 160 Iranian
      adults with T2DM. Therefore, the Persian version of the scale is a valid and
      reliable instrument and can be used in research and clinical settings.

PMID- 30113858
TI  - Use of Some Additives for Improving Mesenchymal Stem Cell Isolation Outcomes in
      Non-Mobilized Peripheral Blood.
AB  - BACKGROUND: The mesenchymal stem cells (MSCs) of peripheral blood (PB) have been
      recognized as a promising source for allogeneic cell therapy. The objective of
      the present study was to isolate and characterize MSCs derived from non-mobilized
      PB, and evaluate their differentiation potential. METHODS: The buffy coat
      mononuclear fractions of the PB were concentrated using the Ficoll-Paque density
      gradient centrifugation and were grown on primary and secondary culture media,
      respectively. The isolated cells were characterized using a multidisciplinary
      approach which was based on morphology, immunophenotyping, gene expression, and
      multipotentiality. Flow cytometry and Reverse transcription polymerase chain
      reaction (RT-PCR) were used to identify the expression of different MSC markers.
      Finally, after culturing in osteogenic and adipogenic induction media, the
      isolated cells were stained by Alizarin red and Oil-Red O. RESULTS: In spite of
      absence of any bone marrow stimulating factor, the isolation approach in this
      study yielded a rather homogeneous and spindle-shaped mononuclear cell population
      (the yield of passage 0 was 0.65 +/- 0.15) that stained positive for CD90, CD105,
      and CD73, and were negative for CD45 and CD34. These cells have high
      proliferative capacity (confirmed by the expression of Oct-4, Nucleostemin, and
      Nanog genes) and were able to differentiate into lineage-specific committed
      cells, when exposed to the appropriate medium. CONCLUSION: Overall, it can be
      concluded that conventional, labour-intensive and time-consuming approaches are
      not necessary in isolating MSCs from PB. This relatively accessible and minimally
      invasive source, PB, represents a good alternative reservoir of homogeneous MSCs
      that could open a new era for practical exploitation in regenerative medicine.

PMID- 30113859
TI  - Comparative Effectiveness Study in Multiple Sclerosis Patients Using Instrumental
      Variable Analysis.
AB  - Randomized clinical trials are considered the ideal source for generation of
      robust evidence for clinical and public health decision making. Estimation of
      treatment effect in observational studies is always subject to varying degrees of
      bias due to lack of random allocation, blindness, precise definition of
      intervention, as well as the existence of potential unknown and unmeasured
      confounding variables. Unlike other conventional methods, instrumental variable
      analysis (IVA), as a method for controlling confounding bias in non-randomized
      studies, attempts to estimate the treatment effect with the least bias even
      without knowing and measuring the potential confounders in the causal pathway. In
      this paper, after understanding the main concepts of this approach, it has been
      attempted to provide a method for analyzing and reporting the IVA for clinical
      researchers through a simplified example. The data used in this paper is derived
      from the clinical data of the follow-up of multiple sclerosis (MS) patients
      treated with two class of interferon.

PMID- 30113860
TI  - The Editor and the Author at Fault: A Lesson From Recent Retractions.
AB  - Many reported scientific misconducts included duplication, data fabrication and
      falsification; but recent fake peer reviews have become strange news for many
      researchers worldwide. Using gmail and other non-academic emails to correspond
      with journals should be highly prohibited. Indeed, the dark part of this story is
      lack of conscience by editors who run some journals. Our suggestion in this paper
      can decrease the chance of repeating similar retractions in close future.

PMID- 30113861
TI  - Photoclinic.

PMID- 30113862
TI  - The Life Story of Dr. Moslem Bahadori, the Pioneering Professor of Tehran School
      of Medicine.

PMID- 30113863
TI  - Influence of morphine on TLR4/ NF-kB signaling pathway of MCF-7 cells.
AB  - Morphine affects the risk of metastasis in cancer. The TLR4 gene promotes
      migration in adenocarcinoma cells. We investigated the effect of morphine on
      TLR4, MyD88 and NF-kappa B-expression and migration. Migration of estrogen
      receptor-positive MCF7 breast cancer cells was studied after 24 and 48 hours
      incubation with morphine, with boyden chamber method. Morphine effect on TLR4,
      MyD88 and NF-kappaB mRNA expression was determined by quantitative Real-Time
      polymerase chain reaction. Migration was reduced at the doses of 0.5 and 5 uM (p
      < 0.05). However, TLR4, MyD88 and NF-kappaBmRNA expression was decreased at the
      doses of 0.5, 5 and 500 uM. Morphine at the dose of 50 uM increased the
      expression of mentioned genes. MCF-7 cell line after 48 hours incubation with the
      dose of 0.5 uM morphine decreased the migration and at the dose of 0.5 uM down
      regulated the mRNA expression of TLR4, MyD88 and NF-kappaB, however, the higher
      doses increased the expression of TLR4, MyD88 and NF-kappaB. Morphine affects
      TLR4expression in breast cancer cell, which depends on time and concentration
      (Tab. 1, Fig. 5, Ref. 24).

PMID- 30113864
TI  - Obstructive Sleep Apnea and the Risk of Cognitive Decline in Older Adults.
AB  - Obstructive sleep apnea causes intermittent hypoxia and sleep fragmentation and
      affects at least 20% of individuals after the age of 65. There is accumulating
      evidence that obstructive sleep apnea may impact brain structure and function.
      Recent cohort studies suggest that it is a risk factor for stroke, mild cognitive
      impairment and Alzheimer's disease. Because prevention through treatment of risk
      factors is currently the main intervention for reducing the incidence of
      dementia, how obstructive sleep apnea affects brain health and whether its
      treatment can slow neurodegeneration are relevant questions. This Perspective
      Article presents the most recent findings on the neurocognitive consequences of
      obstructive sleep apnea in the elderly. We focus on the aging brain and the link
      between obstructive sleep apnea, brain health, cognitive decline and dementia. We
      present how new discoveries from animal models, human sleep experiments, and
      Alzheimer's disease biomarkers point to an active role of disturbed sleep in
      dementia pathogenesis. We show preliminary data on how sex, genetics, physical
      exercise and cognitive reserve can strengthen or weaken the association between
      obstructive sleep apnea and dementia. We present preliminary results of
      obstructive sleep apnea treatment, which can slow, stop or reverse
      neurodegenerative processes accentuated by obstructive sleep apnea, even in
      individuals already affected by a neurodegenerative disease. We propose future
      research directions that include studies on mild/moderate untreated obstructive
      sleep apnea, the evaluation of continuous positive airway pressure treatment to
      slow neurodegeneration and follow-up studies of older patients that measure
      predictors/markers of dementia.

PMID- 30113866
TI  - Poppers-Induced Life-Threatening Methemoglobinemia.

PMID- 30113865
TI  - Associations of Intensive Care Unit Capacity Strain with Disposition and Outcomes
      of Patients with Sepsis Presenting to the Emergency Department.
AB  - RATIONALE: Intensive care unit (ICU) capacity strain refers to the potential
      limits placed on an ICU's ability to provide high-quality care for all patients
      who may need it at a given time. Few studies have investigated how fluctuations
      in ICU capacity strain might influence care outside the ICU. OBJECTIVES: To
      determine whether ICU capacity strain is associated with initial level of
      inpatient care and outcomes for emergency department (ED) patients hospitalized
      for sepsis. METHODS: We performed a retrospective cohort study of patients with
      sepsis admitted from the ED to a medical ward or ICU at three hospitals within
      the University of Pennsylvania Health System between 2012 and 2015. Patients were
      excluded if they required life support therapies, defined as invasive or
      noninvasive ventilatory support or vasopressors, at the time of admission. The
      exposures were four measures of ICU capacity strain at the time of the ED
      disposition decision: ICU occupancy, ICU turnover, ICU census acuity, and ward
      occupancy. The primary outcome was the decision to admit to a ward or to an ICU.
      Secondary analyses assessed the association of ICU capacity strain with in
      hospital outcomes, including mortality. RESULTS: Among 77,142 hospital admissions
      from the ED, 3,067 patients met the study's eligibility criteria. The ICU
      capacity strain metrics varied between and within study hospitals over time. In
      unadjusted analyses, ICU occupancy, ICU turnover, ICU census acuity, and ward
      occupancy were all negatively associated with ICU admission. In the fully
      adjusted model including patient-level covariates, only ICU occupancy remained
      associated with ICU admission (odds ratio, 0.87; 95% confidence interval, 0.79
      0.96; P = 0.005), such that a 10% increase in ICU occupancy (e.g., one additional
      patient in a 10-bed ICU) was associated with a 13% decrease in the odds of ICU
      admission. Among the subset of patients admitted initially from the ED to a
      medical ward, ICU occupancy at the time of admission was associated with
      increased odds of hospital mortality (odds ratio, 1.61; 95% confidence interval,
      1.21-2.14; P = 0.001). CONCLUSIONS: The odds that patients in the ED with sepsis
      who do not require life support therapies will be admitted to the ICU are reduced
      when those ICUs experience high occupancy but not high levels of other previously
      explored measures of capacity strain. Patients with sepsis admitted to the wards
      during times of high ICU occupancy had increased odds of hospital mortality.

PMID- 30113867
TI  - An electromagnetic tracking needle clip: an enabling design for low-cost image
      guided therapy.
AB  - INTRODUCTION: In this study, we hypothesized a disposable low-cost needle clip
      with a specially designed electromagnetic (EM) tracking sensor. It could be
      mounted onto 16- to 22-gauge needles, allowing the tip of the needle to be
      tracked in CT or US image-guided procedures using the Aurora EM tracking system.
      MATERIAL AND METHODS: A 3 D printed EM needle clip case contains a pair of
      specially designed electromagnetic solenoids, positioned perpendicularly to each
      other in order to achieve six degrees of freedom for tracking the tip of the
      needle. The performance of the EM tracking needle clip was evaluated. RESULTS: A
      low-cost 3D-printed disposable needle clip with specially designed EM tracking
      sensors that can be mounted on 16- to 22-gauge needles was designed. This needle
      clip has a 570 mm *600 mm *600 mm (L * W * H) working volume, an error <0.7 mm in
      the axial direction and 0.8 mm in the radial direction. The targeting accuracy
      results are on par with the commercially available EM tracking needles.
      CONCLUSION: The designed EM needle clip provided successful needle tracking, with
      acceptable accuracy, and competitive performance compared to existing products.
      This proposed design may increase the clinical adoption of EM tracking needles
      because of its user-friendly design and low cost.

PMID- 30113868
TI  - EDoP Distance Between Sets of Incomplete Permutations: Application to Bacteria
      Classification Based on Gene Order.
AB  - In this work, we extend measures of distance between permutations to support
      incomplete permutations. Modeling and comparing incomplete permutations are a
      challenging computational problem of practical importance in many applications in
      bioinformatics and social science. We show that the proposed distance measure
      admits a closed-form expression and can be efficiently computed on sets of
      permutations involving several missing elements. We demonstrate the proposed
      method on the classification of bacteria from different phyla based on gene
      order.

PMID- 30113869
TI  - The association between post-traumatic stress disorder and coronary artery
      disease: a meta-analysis.
AB  - OBJECTIVES: There are some psychosocial factors that have similar importance to
      biological factors in the genesis of coronary diseases. However, reasons for high
      rates of coronary heart disease in individuals with post-traumatic stress
      disorder (PTSD) are yet to be fully elucidated. Using a meta-analysis, we
      investigated the longitudinal relationship between PTSD and coronary heart
      disease (CHD) as an independent factor in the aetiology of CHD. METHODS: The
      databases of Medline, EBSCOhost and Psychoinfo were electronically searched for
      relevant articles. RESULTS: The pooled hazard ratio (HR) for the magnitude of the
      relationship between PTSD and CHD was an HR of 1.61, and p-value of p < 0.0005,
      95% confidence interval (CI) [1.46-1.77] before adjustment for depression in nine
      studies ( N = 151,144) that met inclusion criteria. The HR estimates for the
      seven depression-adjusted estimates was 1.46, and a p-value of p < 0.0005, 95%
      CI[0.26-1.69]. CONCLUSIONS: This study demonstrates an association between CHD
      and PTSD.

PMID- 30113870
TI  - Histopathological differences of experimental aneurysms treated with bare
      platinum, fibered, and bioactive coils.
AB  - PURPOSE: To evaluate the histopathological features of experimental aneurysms
      embolized with bare platinum, fibered, and bioactive coils. MATERIAL AND METHODS:
      Twelve experimental aneurysms were constructed in three swine. The aneurysms were
      divided into four groups and were embolized using a bare platinum coil alone (P
      group, n = 2), a bioactive coil alone (B group, n = 2), a combination of fibered
      and bare platinum coils (F/P group, n = 4) and a combination of fibered and
      bioactive coils (F/B group, n = 4). Histopathological data for all aneurysms
      recorded at 63 days were analyzed in terms of neointima formation, fibrosis,
      foreign-body giant-cell infiltration, and organization. RESULTS: Fibrosis was
      significantly greater in group B compared with that in group F/P (p = .02). 
      Inflammation with foreign-body giant-cell infiltration was significantly greater
      in groups F/P and F/B compared with that in groups P and B (p = .007).
      CONCLUSION: The present study revealed that the embolic effect of fibered coils
      was not a thrombus but instead was a foreign-body response in the chronic phase.

PMID- 30113871
TI  - iRNA-2OM: A Sequence-Based Predictor for Identifying 2'-O-Methylation Sites in
      Homo sapiens.
AB  - 2'-O-methylation plays an important biological role in gene expression. Owing to
      the explosive increase in genomic sequencing data, it is necessary to develop a
      method for quickly and efficiently identifying whether a sequence contains the 2'
      O-methylation site. As an additional method to the experimental technique, a
      computational method may help to identify 2'-O-methylation sites. In this study,
      based on the experimental 2'-O-methylation data of Homo sapiens, we proposed a
      support vector machine-based model to predict 2'-O-methylation sites in H.
      sapiens. In this model, the RNA sequences were encoded with the optimal features
      obtained from feature selection. In the fivefold cross-validation test, the
      accuracy reached 97.95%.

PMID- 30113872
TI  - Expression of Noncollagenous Bone Matrix Proteins in Osteoblasts Stimulated by
      Mechanical Stretching in the Cranial Suture of Neonatal Mice.
AB  - We investigated the influence of mechanical stretching on the genetic expression
      pattern of noncollagenous bone matrix proteins in osteoblasts. The cranial
      sutures of neonatal mice were subjected to ex vivo mechanical stretching. In the
      nonstretched control group, as osteoblast differentiation progressed, the
      successive genetic expression of bone sialoprotein (BSP), osteopontin (OPN), and
      osteocalcin (OCN) was detected using in situ hybridization, in that order. In the
      stretched group, the sutures were widened, and after 24 hr of cultivation, a
      large number of osteoblasts and abundant new osteoid were observed on the borders
      of the parietal bones. All new osteoblasts expressed BSP and some of them
      expressed OPN, but very few of them expressed OCN. After 48 hr, more extensive
      presence of osteoid was noted on the borders of the parietal bones, and this
      osteoid was partially mineralized; all osteoblasts on the osteoid surface
      expressed BSP, and more osteoblasts expressed OPN than those after 24 hr
      cultivation. Surprisingly, many of the osteoblasts that did not express OPN,
      expressed OCN. This suggests that when osteoblast differentiation is stimulated
      by mechanical stress, the genetic expression pattern of noncollagenous proteins
      in the newly differentiated osteoblasts is affected.

PMID- 30113873
TI  - Documenting Goals of Care Among Patients With Advanced Cancer: Results of a
      Quality Improvement Initiative.
AB  - PURPOSE: Guidelines recommend that oncologists discuss goals of care (GOC) with
      patients who have advanced cancer and that these patients be referred for early
      palliative care (PC). An audit of practice between 2010 and 2015 at the Cancer
      Centre of Southeastern Ontario suggested that these rates were suboptimal. We
      sought to improve the rate of documentation of GOC and referral to PC through the
      implementation of a quality improvement (QI) initiative. METHODS: Patients
      receiving palliative systemic treatment of lung, pancreatic, colorectal, and
      breast cancer were identified via electronic pharmacy records and the electronic
      patient care system. Using the Define, Measure, Analyze, Improve, Control QI
      methodology, we drafted a guideline for GOC documentation and PC referral and
      designed a standardized documentation system. E-mail reminders were sent to
      physicians and a QI scorecard was displayed to document overall and individual
      physician rates of GOC documentation. Data were analyzed monthly and presented on
      statistical process control P charts. RESULTS: Between May 2016 and November
      2017, a total of 303 unique patients were identified (52%, 21%, 17%, and 10% with
      lung, breast, colorectal, and pancreatic cancer, respectively). GOC documentation
      increased significantly over the study period (baseline, 0%; passive phase, 3%;
      active phase, 31%); this increase was likely because of our intervention. PC
      referral rates also increased over the study period (baseline, 36%; passive
      phase, 35%; active phase 48%). We did not identify any patient, physician, or
      disease factors that were associated with GOC discussion or referral to PC.
      CONCLUSION: Our QI initiative was successful in improving rates of GOC
      documentation in patients with advanced cancer.

PMID- 30113874
TI  - Cell cycle-dependent force transmission in cancer cells.
AB  - The generation of traction forces and their transmission to the extracellular
      environment supports the disseminative migration of cells from a primary tumor.
      In cancer cells, the periodic variation of nuclear stiffness during the cell
      cycle provides a functional link between efficient translocation and
      proliferation. However, the mechanical framework completing this picture remains
      unexplored. Here, the Fucci2 reporter was expressed in various human epithelial
      cancer cells to resolve their cell cycle phase transition. The corresponding
      tractions were captured by a recently developed reference-free confocal traction
      force microscopy platform. The combined approach was conducive to the analysis of
      phase-dependent force variation at the level of individual integrin contacts.
      Detected forces were invariably higher in the G1 and early S phases than in the
      ensuing late S/G2, and locally colocalized with high levels of paxillin
      phosphorylation. Perturbation of paxillin phosphorylation at focal adhesions,
      obtained through the biochemical inhibition of focal adhesion kinase (FAK) or the
      transfection of nonphosphorylatable or phosphomimetic paxillin mutants,
      significantly diminished the force transmitted to the substrate. These data
      demonstrate a reproducible modulation of force transmission during the cell cycle
      progression of cancer cells, instrumental to their invasion of dense
      environments. In addition, they delineate a model in which paxillin
      phosphorylation supports the mechanical maturation of adhesions relaying forces
      to the substrate.

PMID- 30113875
TI  - Organoids for Drug Discovery and Personalized Medicine.
AB  - A wide variety of organs are in a dynamic state, continuously undergoing renewal
      as a result of constant growth and differentiation. Stem cells are required
      during these dynamic events for continuous tissue maintenance within the organs.
      In a steady state of production and loss of cells within these tissues, new cells
      are constantly formed by differentiation from stem cells. Today, organoids
      derived from either adult stem cells or pluripotent stem cells can be grown to
      resemble various organs. As they are similar to their original organs, organoids
      hold great promise for use in medical research and the development of new
      treatments. Furthermore, they have already been utilized in the clinic, enabling
      personalized medicine for inflammatory bowel disease. In this review, I provide
      an update on current organoid technology and summarize the application of
      organoids in basic research, disease modeling, drug development, personalized
      treatment, and regenerative medicine. Expected final online publication date for
      the Annual Review of Pharmacology and Toxicology Volume 59 is January 6, 2019.
      Please see http://www.annualreviews.org/page/journal/pubdates for revised
      estimates.

PMID- 30113876
TI  - Low efficacy using the 256-Hz tuning fork when evaluating the influence of
      somatosensation in balance control for relatively healthy elderly.
AB  - BACKGROUND: Diminished foot somatosensation contributes to balance deficits and
      increased fall risk. However, it remains unclear if the 256-Hz tuning fork is
      adequate to measure, in the outpatient clinical setting, somatosensation in
      relatively healthy elderly. AIMS/OBJECTIVES: To evaluate the performance of the
      256-Hz tuning fork compared to other measures of somatosensation and balance.
      MATERIAL AND METHODS: Thirty-six subjects (mean 69.4 +/- 5.3 years) were
      allocated into four 256-Hz tuning fork sensation groups (TFSG) based on their
      ability to detect vibration at the first metatarsal, malleolus, tibia or no
      sites. A biothesiometer measured vibration perception thresholds (VPTs) and 20
      monofilaments tactile pressure sensation thresholds (TPSTs). Balance was
      evaluated with posturography, functional balance tests and questionnaires.
      RESULTS: There were no significant differences in age, VPTs or TPSTs between the
      four TFSGs, nor in outcome of functional balance tests, posturography and
      questionnaires. Very few significant associations were found between TFSGs and
      VPTs, TPSTs, functional balance tests, posturography and questionnaires.
      CONCLUSIONS AND SIGNIFICANCE: Somatosensation measured with a 256-Hz tuning fork
      seems to be a minor determinant for balance and thus superfluous when evaluating
      the importance of vibration perception for balance control in relatively healthy
      elderly.

PMID- 30113877
TI  - Fully endoscopic laser stapedotomy: is it comparable with microscopic surgery?
AB  - BACKGROUND: Microscopic stapedotomy is very successful and has long history, but
      it still has some constraints. Thus, otoendoscopy is increasingly popular
      nowadays. AIMS/OBJECTIVES: The retrospective review study was to investigate the
      role of endoscopic laser stapedotomy in treating patients with otosclerosis.
      MATERIALS AND METHODS: Seventeen patients who received endoscopic laser
      stapedotomy from April 2014 to July 2017 were enrolled and compared to 13
      patients who had microscopic stapedotomy from February 2009 to March 2012. The
      anatomical structures, operative time, and postoperative hearing outcomes were
      assessed in two groups. Relation between external acoustic canal and operative
      time was also analyzed. RESULTS: Using an endoscope, the operative field was
      clear, with easily identified anatomy, without need to sacrifice bony structures.
      The operative time was significantly longer in the endoscopic group in 2014 and
      decreased in the following years. There was no significant difference of hearing
      improvements between the two groups. There was a weak correlation between the
      width of the external auditory canal and the operative time. CONCLUSIONS AND
      SIGNIFICANCE: Fully endoscopic stapes surgery is a feasible and safe surgical
      technique and results in satisfactory hearing outcomes. However, surgeons take
      longer to master the technique and to achieve shorter endoscopic operative times.

PMID- 30113878
TI  - Do emotional responses to food images differ within different types of eating
      disorders?
AB  - OBJECTIVES: To investigate emotional responses to food images in women with
      eating disorders (EDs) and healthy controls (HCs); and in underweight individuals
      post weight-restoration. METHODS: Women (>14 years) with ( n = 139) and without (
      n = 41) an ED rated food images evoking fear, disgust and happiness on a three
      visual-analogue scale. Underweight participants viewed the images at two time
      points; pre- and post-weight-restoration. RESULTS: HCs were significantly
      happier, less fearful/anxious prior to viewing the images compared with EDs.
      Negative emotional responses when viewing images were significantly greater ( p <
      .001) in EDs compared with HCs; however, groups did not differ in happiness.
      Emotional responses were not significantly different within the ED groups. At
      post weight-restoration, individuals were significantly less anxious/disgusted
      when viewing the images. CONCLUSIONS: The importance of considering emotional
      responses when discussing food consumption in EDs trans-diagnostically is
      highlighted. Weight recovery reduces negative food responses, although responses
      remained high in comparison to HCs.

PMID- 30113879
TI  - AMH prevents primordial ovarian follicle loss and fertility alteration in
      cyclophosphamide-treated mice.
AB  - The follicular ovarian reserve, constituted by primordial follicles (PMF), is
      established early in life, then keeps declining regularly along reproductive
      life. The maintenance of a normal female reproductive function implies the
      presence of a vast amount of dormant PMF. This process involves a continuous
      repression of PMF activation into early growing follicle through the balance
      between factors activating the initiation of follicular growth, mainly actors of
      the PI3K signaling pathway, and inhibiting factors such as anti-Mullerian hormone
      (AMH). Any disruption of this balance may induce follicle depletion and
      subsequent infertility. It has been recently proposed that cyclophosphamide (Cy),
      an alkylating agent commonly used for treating breast cancer, triggers PMF
      activation, further leading to premature ovarian insufficiency. Preventing
      chemotherapy-induced ovarian dysfunction might represent an interesting option
      for preserving optimal chances of natural or medically assisted conceptions after
      healing. The aim of the present study was to evaluate, in a model of Cy-treated
      pubertal mice, whether AMH administration might restrain PMF depletion. The
      counting of the total PMF number within mouse ovaries showed that recombinant AMH
      prevented Cy-induced PMF loss. Western blot analysis revealed activation of PI3K
      signaling pathway after Cy administration. After AMH injection, FOXO3A
      phosphorylation, a main actor of PMF activation, was significantly decreased.
      Taken together, these results support a protective role of AMH against Cy-induced
      follicular loss. We also provide evidence for a possible role of autophagy in the
      preservation of follicular pool reserve. Therefore, concomitant recombinant AMH
      administration during chemotherapy might offer a new option for preserving young
      patients' fertility.-Sonigo, C., Beau, I., Grynberg, M., Binart, N. AMH prevents
      primordial ovarian follicle loss and fertility alteration in cyclophosphamide
      treated mice.

PMID- 30113880
TI  - Two intrauterine programming mechanisms of adult hypercholesterolemia induced by
      prenatal nicotine exposure in male offspring rats.
AB  - Epidemiologic studies showed that low birth weight is associated with high
      cholesterol and an increased risk of cardiovascular diseases in adulthood. This
      study aimed to elucidate the intrauterine programming mechanisms of adult
      hypercholesterolemia. The results showed that prenatal nicotine exposure (PNE)
      caused intrauterine growth retardation and hypercholesterolemia in male adult
      offspring rats. Hepatic cholesterol synthesis and output were deceased in utero
      but increased in adults; hepatic reverse cholesterol transport (RCT) persistently
      deceased before and after birth. Meanwhile, PNE elevated serum corticosterone
      level and decreased hepatic IGF1 pathway activity in male fetuses, whereas
      converse changes were observed in male adults. The chronic stress model and
      cortisol-treated HepG2 cells verified that excessive glucocorticoid (GC)-induced
      GC-IGF1 axis programming enhanced hepatic cholesterol synthesis and output. In
      addition, PNE decreased the expression of specific protein 1 and P300 enrichment
      and H3K27 acetylation at the promoter region of genes responsible for RCT both in
      fetal and adult, male livers and reduced expression of those genes, similar
      alterations were also confirmed in cortisol-treated HepG2 cells, suggesting that
      excessive GC-related programming induced continuous RCT reduction by epigenetic
      modification. Taken together, the "2-programming" approach discussed above may
      ultimately contribute to the development of hypercholesterolemia in male adult
      offspring.-Zhou, J., Zhu, C., Luo, H., Shen, L., Gong, J., Wu, Y., Magdalou, J.,
      Chen, L., Guo, Y., Wang, H. Two intrauterine programming mechanisms of adult
      hypercholesterolemia induced by prenatal nicotine exposure in male offspring
      rats.

PMID- 30113881
TI  - Calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation contributes to
      the pathogenesis of experimental colitis via inhibition of intestinal epithelial
      cell proliferation.
AB  - The incidence and prevalence of inflammatory bowel disease (IBD) are increasing
      worldwide. IBD is known to be multifactorial, but inflammatory signaling within
      the intestinal epithelium and a subsequent failure of the intestinal epithelial
      barrier have been shown to play essential roles in disease pathogenesis. CaMKIV
      is a multifunctional protein kinase associated with inflammation and cell cycle
      regulation. CaMKIV has been extensively studied in autoimmune diseases, but a
      role in idiopathic intestinal inflammation has not been described. In this study,
      active CaMKIV was highly expressed within the intestinal epithelium of humans
      with ulcerative colitis and wild-type (WT) mice with experimental induced
      colitis. Clinical disease severity directly correlates with CaMKIV activation, as
      does expression of proinflammatory cytokines and histologic features of colitis.
      In WT mice, CaMKIV activation is associated with increases in expression of 2
      cell cycle proarrest signals: p53 and p21. Cell cycle arrest inhibits
      proliferation of the intestinal epithelium and ultimately results in compromised
      intestinal epithelial barrier integrity, further perpetuating intestinal
      inflammation during experimental colitis. Using a CaMKIV null mutant mouse, we
      demonstrate that a loss of CaMKIV protects against murine DSS colitis. Small
      molecules targeting CaMKIV activation may provide therapeutic benefit for
      patients with IBD.-Cunningham, K. E., Novak, E. A., Vincent, G., Siow, V. S.,
      Griffith, B. D., Ranganathan, S., Rosengart, M. R., Piganelli, J. D., Mollen, K.
      P. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) activation contributes
      to the pathogenesis of experimental colitis via inhibition of intestinal
      epithelial cell proliferation.

PMID- 30113882
TI  - Stabilization of p27Kip1/CDKN1B by UBCH7/UBE2L3 catalyzed ubiquitinylation: a new
      paradigm in cell-cycle control.
AB  - Ubiquitinylation drives many cellular processes by targeting proteins for
      proteasomal degradation. Ubiquitin conjugation enzymes promote ubiquitinylation
      and, thus, degradation of protein substrates. Ubiquitinylation is a well-known
      posttranslational modification controlling cell-cycle transitions and levels
      or/and activation levels of ubiquitin-conjugating enzymes change during
      development and cell cycle. Progression through the cell cycle is tightly
      controlled by CDK inhibitors such as p27Kip1. Here we show that, in contrast to
      promoting its degradation, the ubiquitin-conjugating enzyme UBCH7/UBE2L3
      specifically protects p27Kip1 from degradation. Overexpression of UBCH7/UBE2L3
      stabilizes p27Kip1 and delays the G1-to-S transition, while depletion of
      UBCH7/UBE2L3 increases turnover of p27Kip1. Levels of p21Cip1/Waf1, p57Kip2,
      cyclin A and cyclin E, all of which are also involved in regulating the G1/S
      transition are not affected by UBCH7/UBE2L3 depletion. The effect of UBCH7/UBE2L3
      on p27Kip1 is not due to alteration of the levels of any of the ubiquitin ligases
      known to ubiquitinylate p27Kip1. Rather, UBCH7/UBE2L3 catalyzes the conjugation
      of heterotypic ubiquitin chains on p27Kip1 that are proteolytically incompetent.
      These data reveal new controls and concepts about the ubiquitin proteasome system
      in which a ubiquitin-conjugating enzyme selectively inhibits and may even
      protect, rather than promote degradation of a crucial cell-cycle regulatory
      molecule.-Whitcomb, E. A., Tsai, Y. C., Basappa, J., Liu, K., Le Feuvre, A. K.,
      Weissman, A. M., Taylor, A. Stabilization of p27Kip1/CDKN1B by UBCH7/UBE2L3
      catalyzed ubiquitinylation: a new paradigm in cell-cycle control.

PMID- 30113884
TI  - Cell tension and mechanical regulation of cell volume.
AB  - Animal cells use an unknown mechanism to control their growth and physical size.
      Here, using the fluorescence exclusion method, we measure cell volume for
      adherent cells on substrates of varying stiffness. We discover that the cell
      volume has a complex dependence on substrate stiffness and is positively
      correlated with the size of the cell adhesion to the substrate. From a mechanical
      force-balance condition that determines the geometry of the cell surface, we find
      that the observed cell volume variation can be predicted quantitatively from the
      distribution of active myosin through the cell cortex. To connect cell mechanical
      tension with cell size homeostasis, we quantified the nuclear localization of
      YAP/TAZ, a transcription factor involved in cell growth and proliferation. We
      find that the level of nuclear YAP/TAZ is positively correlated with the average
      cell volume. Moreover, the level of nuclear YAP/TAZ is also connected to cell
      tension, as measured by the amount of phosphorylated myosin. Cells with greater
      apical tension tend to have higher levels of nuclear YAP/TAZ and a larger cell
      volume. These results point to a size-sensing mechanism based on mechanical
      tension: the cell tension increases as the cell grows, and increasing tension
      feeds back biochemically to growth and proliferation control.

PMID- 30113883
TI  - Synthetic cementum protein 1-derived peptide regulates mineralization in vitro
      and promotes bone regeneration in vivo.
AB  - The use of recombinant proteins has revolutionized the development of biologic
      pharmaceuticals; however, they are not free of complications. Some have very high
      molecular weight, some demonstrate in vivo instability, and the high cost of
      producing them remains a major problem. On the other hand, it has been shown that
      peptides derived from active domains keep their biologic activity and can trigger
      events, such as osteogenesis and bone regeneration. Small peptides are
      advantageous because of their ease of synthesis and handling and their low
      immunogenic activity. The purpose of this study was to investigate the functions
      of a synthetic peptide, cementum protein 1-peptide1 (CEMP-1-p1), both in vitro
      and in vivo. Our results show that CEMP-1-p1 significantly enhanced the
      proliferation and differentiation of human periodontal ligament cells toward a
      mineralizing-like phenotype, as evidenced by increasing alkaline phosphatase
      (ALP)-specific activity and osterix, runt-related transcription factor (RUNX)-2,
      integrin binding sialoprotein, bone morphogenetic protein-2, osteocalcin, and
      cementum protein (CEMP)-1 expression at mRNA and protein levels. In vivo assays
      performed through standardized critical-size calvarial defects in rats treated
      with CEMP-1-p1 resulted in newly formed bone after 30 and 60 d. These data
      demonstrate that CEMP-1-p1 is an effective bioactive peptide for bone tissue
      regeneration. The application of this bioactive peptide may lead to implementing
      new strategies for the regeneration of bone and other mineralized tissues.
      Correa, R., Arenas, J., Montoya, G., Hoz, L., Lopez, S., Salgado, F., Arroyo, R.,
      Salmeron, N., Romo, E., Zeichner-David, M., Arzate, H. Synthetic cementum protein
      1-derived peptide regulates mineralization in vitro and promotes bone
      regeneration in vivo.

PMID- 30113885
TI  - Prescription Drug Coverage and Outcomes of Myeloma Therapy Among Medicare
      Beneficiaries.
AB  - PURPOSE: Novel parenteral (bortezomib) and oral (lenalidomide) therapies have
      improved survival in myeloma, but the standard Medicare benefit covers only
      parenteral drugs. We examined the association between prescription drug coverage,
      receipt of therapy, and survival among Medicare beneficiaries with myeloma.
      METHODS: Using SEER-Medicare data, we identified enrollment in a Medicare Part D
      plan (PDP) or other creditable prescription drug coverage (OCC) among 9,755
      beneficiaries who were diagnosed with myeloma in 2006 to 2011. We examined the
      receipt of active myeloma therapy and that of classic cytotoxic agents or
      bortezomib as first-line regimen and overall survival. We report relative risk
      (RR) for binary outcome comparisons and 3-year restricted mean survival time
      (RMST) ratios, with 95% CI, adjusting for baseline patient- and disease-related
      characteristics. Beneficiaries with diffuse large B-cell lymphoma, a cancer that
      is uniformly treated with parenteral chemotherapy, served as a comparison cohort.
      RESULTS: Compared with beneficiaries without prescription drug coverage, PDP or
      OCC enrollees were more likely to receive active myeloma care, and PDP enrollees
      were less frequently treated with parenteral agents (adjusted RR, 0.86; 95% CI,
      0.80 to 0.93) or classic cytotoxic agents in particular (RR, 0.62; 95% CI, 0.51
      to 0.76). Overall survival was significantly better for beneficiaries with PDP
      coverage (adjusted RMST ratio, 1.16; 95% CI, 1.11 to 1.20) or OCC (RMST ratio,
      1.16; 95% CI, 1.12 to 1.21). In contrast, we observed no survival differences by
      prescription drug coverage status in the control cohort with lymphoma.
      CONCLUSION: Prescription drug coverage is associated with decreased use of
      classic cytotoxic chemotherapy and better survival among Medicare beneficiaries
      with myeloma, which suggests improved access to all existing treatment options.
      As oral targeted agents increasingly replace parenteral chemotherapy in oncology,
      adjustments in coverage policy are needed to ensure access to optimal treatment.

PMID- 30113886
TI  - Frequency of Germline Mutations in Cancer Susceptibility Genes in Malignant
      Mesothelioma.
AB  - PURPOSE: The aim of the current study was to determine the prevalence and
      clinical predictors of germline cancer susceptibility mutations in patients with
      malignant mesothelioma (MM). METHODS: We performed targeted capture and next
      generation sequencing of 85 cancer susceptibility genes on germline DNA from 198
      patients with pleural, peritoneal, and tunica vaginalis MM. RESULTS: Twenty-four
      germline mutations were identified in 13 genes in 23 (12%) of 198 patients. BAP1
      mutations were the most common (n = 6; 25%). The remaining were in genes involved
      in DNA damage sensing and repair (n = 14), oxygen sensing (n = 2), endosome
      trafficking (n = 1), and cell growth (n = 1). Pleural site (odds ratio [OR],
      0.23; 95% CI, 0.10 to 0.58; P < .01), asbestos exposure (OR, 0.28; 95% CI, 0.11
      to 0.72; P < .01), and older age (OR, 0.95; 95% CI, 0.92 to 0.99; P = .01) were
      associated with decreased odds of carrying a germline mutation, whereas having a
      second cancer diagnosis (OR, 3.33; 95% CI, 1.22 to 9.07; P = .02) significantly
      increased the odds. The odds of carrying a mutation in BAP1 (OR, 1,658; 95% CI,
      199 to 76,224; P < .001), BRCA2 (OR, 5; 95% CI, 1.0 to 14.7; P = .03), CDKN2A
      (OR, 53; 95% CI, 6 to 249; P < .001), TMEM127 (OR, 88; 95% CI, 1.7 to 1,105; P =
      .01), VHL (OR, 51; 95% CI, 1.1 to 453; P = .02), and WT1 (OR, 20; 95% CI, 0.5 to
      135; P = .049) were significantly higher in MM cases than in a noncancer control
      population. Tumor sequencing identified mutations in a homologous recombination
      pathway gene in 52% (n = 29 of 54). CONCLUSION: A significant proportion of
      patients with MM carry germline mutations in cancer susceptibility genes,
      especially those with peritoneal MM, minimal asbestos exposure, young age, and a
      second cancer diagnosis. These data support clinical germline genetic testing for
      patients with MM and provide a rationale for additional investigation of the
      homologous recombination pathway in MM.

PMID- 30113887
TI  - Organelle Formation in Bacteria and Archaea.
AB  - Uncovering the mechanisms that underlie the biogenesis and maintenance of
      eukaryotic organelles is a vibrant and essential area of biological research. In
      comparison, little attention has been paid to the process of compartmentalization
      in bacteria and archaea. This lack of attention is in part due to the common
      misconception that organelles are a unique evolutionary invention of the
      "complex" eukaryotic cell and are absent from the "primitive" bacterial and
      archaeal cells. Comparisons across the tree of life are further complicated by
      the nebulous criteria used to designate subcellular structures as organelles.
      Here, with the aid of a unified definition of a membrane-bounded organelle, we
      present some of the recent findings in the study of lipid-bounded organelles in
      bacteria and archaea.

PMID- 30113888
TI  - Prostate Volume Segmentation in TRUS using Hybrid Edge-Bhattacharyya Active
      Surfaces.
AB  - OBJECTIVE: We present a new hybrid edge and region-based parametric deformable
      model, or active surface, for prostate volume segmentation in transrectal
      ultrasound (TRUS) images. METHODS: Our contribution is threefold. First, we
      develop a new edge detector derived from the radial bas-relief approach, allowing
      for better scalar prostate edge detection in low contrast configurations. Second,
      we combine an edge-based force derived from the proposed edge detector with a new
      region-based force driven by the Bhattacharyya gradient flow and adapted to the
      case of parametric active surfaces. Finally, we develop a quasi-automatic
      initialization technique for deformable models by analyzing the profiles of the
      proposed edge detector response radially to obtain initial landmark points
      towards which an initial surface model is warped. RESULTS: We validate our method
      on a set of 36 TRUS images for which manual delineations were performed by two
      expert radiation oncologists, using a wide variety of quantitative metrics. The
      proposed hybrid model achieved state-of-the art segmentation accuracy.
      CONCLUSION: Results demonstrate the interest of the proposed hybrid framework for
      accurate prostate volume segmentation. SIGNIFICANCE: This paper presents a
      modular framework for accurate prostate volume segmentation in TRUS, broadening
      the range of available strategies to tackle this open problem.

PMID- 30113889
TI  - A novel minimally-occlusive cuff method utilizing ultrasound vascular imaging for
      stress-free blood pressure measurement: a-proof-of-concept study.
AB  - OBJECTIVE: Occlusive cuff inflation in ambulatory blood pressure (BP) monitoring
      disturbs the daily life of the user, and affects efficacy of monitoring. To
      overcome this limitation, we have developed a novel minimally-occlusive cuff
      method for stress-free measurement of BP. This study aimed to experimentally
      evaluate the reliability of this method. Methods In this method, a thin-plate
      type ultrasound probe placed between the cuff and the skin is used to measure the
      ultrasonic dimension of the artery. Analyzing the arterial dimension and the cuff
      pressure measured during mild cuff inflation (cuff pressure $?lt50$ mmHg) allows
      estimation of systolic ($?rm SBP_e$) and diastolic BP ($?rm DBP_e$). We evaluated
      this method in 6 anesthetized dogs by attaching the cuff with the probe to the
      right thigh to get $?rm SBP_e$ and $?rm DBP_e$. We measured reference SBP and DBP
      using an intra-arterial catheter and determined the pulse arrival time (PAT)
      commonly employed in cuff-less BP monitoring. BP was perturbed by infusing
      noradrenaline or nitroprusside. RESULTS: $?rm DBP_e$ correlated tightly with DBP
      with a coefficient of determination ($?rm R^2$) of 0.85 +/- 0.08, and predicted
      DBP with a bias of 3.9 +/- 7.9 mmHg after a one-time calibration. Reciprocal of
      PAT correlated poorly with DBP ($?rm R^2$ = 0.49 +/- 0.17), and predicted DBP
      less accurately than this method. $?rm SBP_e$ correlated well with SBP ($?rm R^2$
      = 0.78 +/- 0.08) Conclusion: This method reliably tracks BP changes without
      occlusive cuff inflation. Once calibrated, this method measures DBP accurately.
      SIGNIFICANCE: This method has the potential for stress-free BP measurement in
      ambulatory BP monitoring.

PMID- 30113890
TI  - Generation of patient-specific cardiac vascular networks: a hybrid image-based
      and synthetic geometric model.
AB  - OBJECTIVE: In this paper, we propose an algorithm for the generation of a patient
      specific cardiac vascular network starting from segmented epicardial vessels down
      to the arterioles. METHOD: We extend a tree generation method based on
      satisfaction of functional principles, named Constrained Constructive
      Optimization (CCO), to account for multiple, competing vascular trees. The
      algorithm simulates angiogenesis under vascular volume minimization with flow
      related and geometrical constraints adapting the simultaneous tree growths to
      patient priors. The generated trees fill the entire left ventricle myocardium up
      to the arterioles. RESULTS: From actual vascular tree models segmented from CT
      images, we generated networks with 6000 terminal segments for 6 patients. These
      networks contain between 33 and 62 synthetic trees. All vascular models match
      morphometry properties previously described. CONCLUSION AND SIGNIFICANCE: Image
      based models derived from CT angiography are being used clinically to simulate
      blood flow in the coronary arteries of individual patients to aid in the
      diagnosis of disease and planning treatments. However, image resolution limits
      vessel segmentation to larger epicardial arteries. The generated model can be
      used to simulate blood flow and derived quantities from the aorta into the
      myocardium. This is an important step for diagnosis an treatment planning of
      coronary artery disease.

PMID- 30113891
TI  - Regional Multi-view Learning for Cardiac Motion Analysis: Application to
      Identification of Dilated Cardiomyopathy Patients.
AB  - OBJECTIVE: The aim of this paper is to describe an automated diagnostic pipeline
      which uses as input only ultrasound (US) data, but is at the same time informed
      by a training database of multimodal magnetic resonance (MR) and US image data.
      METHODS: We create a multimodal cardiac motion atlas from 3D MR and 3D US data
      followed by multi-view machine learning algorithms to combine and extract the
      most meaningful cardiac descriptors for classification of dilated cardiomyopathy
      (DCM) patients using US data only. More specifically, we propose two algorithms
      based on: multi-view linear discriminant analysis (MLDA) and multi-view Laplacian
      support vector machines (MvLapSVM). Furthermore, a novel regional multi-view
      approach is proposed to exploit the regional relationships between the two
      modalities. RESULTS: We evaluate our pipeline on the classification task of
      discriminating between normals and DCM patients. Results show that the use of
      multi-view classifiers together with a cardiac motion atlas results in a
      statistically significant improvement in accuracy compared to classification
      without the multimodal atlas. MvLapSVM was able to achieve the highest accuracy
      for both the global approach (92.71%) and the regional approach (94.32%).
      CONCLUSION: Our work represents an important contribution to the understanding of
      cardiac motion, which is an important aid in the quantification of the
      contractility and function of the left ventricular myocardium. SIGNIFICANCE: The
      intended workflow of the developed pipeline is to make use of the prior knowledge
      from the multimodal atlas to enable robust extraction of indicators from 3D US
      images for detecting DCM patients.

PMID- 30113892
TI  - Solid Mathematical Marbling.
AB  - Years of research have been devoted to computer-generated two-dimensional
      marbling. However, three-dimensional marbling has yet to be explored. In this
      paper, we present mathematical marbling of three-dimensional solids which
      supports a compact random-access vector representation. Our solid marbling
      textures are created by composing closed-form 3D pattern tool functions. These
      tool functions are an injection function and five deformation functions. The
      injection function is used to generate basic patterns, and the deformation
      functions are responsible for transforming the basic pattern into complex
      marbling effects. The resulting representation is feature preserving and
      resolution-independent. Our approach can render high-quality images preserving
      both the sharp features and the smooth color variations of a solid texture. When
      implemented on the GPU, our representation enables efficient color evaluation
      during the real-time solid marbling texture mapping. The color of a point in the
      volume space is computed by the 3D pattern tool functions from its coordinates.
      Our method consumes very little memory because only the mathematical functions
      and their corresponding parameters are stored. In addition, we develop an
      intuitive user interface and a genetic algorithm to facilitate the solid marbling
      texture authoring process. We demonstrate the effectiveness of our approach
      through various solid marbling textures and 3D objects carved from them.

PMID- 30113893
TI  - Lamplight Stabilization for GPS Rb Atomic Clocks via RF-Power Control.
AB  - Recent evidence indicates that the signal-in-space user-range-error (SIS-URE) for
      GPS is strongly influenced by the satellite atomic clock's rubidium (Rb)
      lamplight intensity jumps. Following a proposal by Bloom and Bell, we have
      implemented RF-power control of an RF-discharge lamp of the type employed in Rb
      atomic frequency standards (RAFS). Since Rb lamplight intensity jumps are mapped
      onto the clock's output frequency via the light-shift effect, stabilization of
      the Rb light emitted by the lamp has the potential to significantly improve the
      RAFS' long-term frequency stability, and hence the GPS SIS-URE. Here, we not only
      demonstrate that RF-power control of the discharge lamp is possible, but also
      that by employing such control the fluctuations in Rb lamplight intensity can be
      reduced by orders of magnitude, providing a pathway for significant improvement
      in global navigation satellite systems.

PMID- 30113894
TI  - Characterization of Elastic Modulus Across the (Al1-xScx)N System Using DFT and
      Substrate-Effect-Corrected Nanoindentation.
AB  - Knowledge of accurate values of elastic modulus of (Al1-xScx)N is required for
      design of piezoelectric resonators and related devices. Thin films of (Al1-xScx)N
      across the entire composition space are deposited and characterized. Accuracy of
      modulus measurements is improved and quantified by removing the influence of
      substrate effects and by direct comparison of experimental results with density
      functional theory calculations. The 5%-30% Sc compositional range is of
      particular interest for piezoelectric applications and is covered at higher
      compositional resolution here than in previous work. The reduced elastic modulus
      is found to decrease by as much as 40% with increasing Sc concentration in the
      wurtzite phase according to both experimental and computational techniques,
      whereas Sc-rich rocksalt-structured films exhibit little variation in modulus
      with composition.

PMID- 30113895
TI  - High Spatial-Temporal Resolution Reconstruction of Plane-Wave Ultrasound Images
      With a Multichannel Multiscale Convolutional Neural Network.
AB  - In recent years, plane-wave imaging (PWI) has attracted considerable attention
      because of its high temporal resolution. However, the low spatial resolution of
      PWI limits its clinical applications, which has inspired various studies on the
      high spatial resolution reconstruction of PW ultrasound images. Although
      compounding methods and traditional high spatial resolution reconstruction
      approaches can improve the image quality, these techniques decrease the temporal
      resolution. Since learning methods can fully reserve the high temporal resolution
      of PW ultrasounds, a novel convolutional neural network (CNN) model for the high
      spatial-temporal resolution reconstruction of PW ultrasound images is proposed in
      this paper. Considering the multiangle form of PW data, a multichannel model is
      introduced to produce balanced training. To combine local and contextual
      information, the multiscale model is adopted. These two innovations constitute
      our multichannel and multiscale CNN (MMCNN) model. Compared with traditional CNN
      methods, the proposed model uses a two-stage structure in which a cascading
      wavelet postprocessing stage is combined with the trained MMCNN model. Cascading
      wavelet postprocessing aims to preserve speckle information. Furthermore, a
      feedback system is appended to the iteration process of the network training to
      solve the overfitting problem and help produce convergence. Based on these
      improvements, an end-to-end mapping is established between a single-angle B-mode
      PW image and its corresponding multiangle compounded, high-resolution image. The
      experiments were conducted on simulated, phantom, and real human data. The
      advantages of our proposed method were compared with a coherent PW compounding
      method, a conventional maximum a posteriori-based high spatial resolution
      reconstruction method, and a 2-D CNN compounding method, and the results verified
      that our approach is capable of attaining a better temporal resolution and
      comparable spatial resolution. In clinical usage, the proposed method is equipped
      to satisfy with many ultrafast imaging applications, which require high spatial
      temporal resolution. i.

PMID- 30113896
TI  - Personalized Exposure Control Using Adaptive Metering and Reinforcement Learning.
AB  - We propose a reinforcement learning approach for real-time exposure control of a
      mobile camera that is personalizable. Our approach is based on Markov Decision
      Process (MDP). In the camera viewfinder or live preview mode, given the current
      frame, our system predicts the change in exposure so as to optimize the trade-off
      among image quality, fast convergence, and minimal temporal oscillation. We model
      the exposure prediction function as a fully convolutional neural network that can
      be trained through Gaussian policy gradient in an end-to-end fashion. As a
      result, our system can associate scene semantics with exposure values; it can
      also be extended to personalize the exposure adjustments for a user and device.
      We improve the learning performance by incorporating an adaptive metering module
      that links semantics with exposure. This adaptive metering module generalizes the
      conventional spot or matrix metering techniques. We validate our system using the
      MIT FiveK and our own datasets captured using iPhone 7 and Google Pixel.
      Experimental results show that our system exhibits stable real-time behavior
      while improving visual quality compared to what is achieved through native camera
      control.

PMID- 30113897
TI  - Inferring Spatial Organization of Individual Topologically Associated Domains via
      Piecewise Helical Model.
AB  - The recently developed Hi-C technology enables a genome-wide view of chromosome
      spatial organizations, and has shed deep insights into genome structure and
      genome function. However, multiple sources of uncertainties make downstream data
      analysis and interpretation challenging. Specifically, statistical models for
      inferring three-dimensional (3D) chromosomal structure from Hi-C data are far
      from their maturity. Most existing methods are highly over-parameterized, lacking
      clear interpretations, and sensitive to outliers. In this study, we propose a
      parsimonious, easy to interpret, and robust piecewise helical model for the
      inference of 3D chromosomal structure of individual topologically associated
      domain from Hi-C data. When applied to a real Hi-C dataset, the piecewise helical
      model not only achieves much better model fitting than existing models, but also
      reveals that geometric properties of chromatin spatial organization are closely
      related to genome function.

PMID- 30113898
TI  - Incorporating prior knowledge about genetic variants into the analysis of genetic
      association data: An empirical Bayes approach.
AB  - In a genome-wide association study (GWAS), the probability that a single
      nucleotide polymorphism (SNP) is not associated with a disease is its local false
      discovery rate (LFDR). The LFDR for each SNP is relative to a reference class of
      SNPs. For example, the LFDR of an exonic SNP can vary widely depending on whether
      it is considered relative to the separate reference class of other exonic SNPs or
      relative to the combined reference class of all SNPs in the data set. As a
      result, the analysis of the data based on the combined reference class might
      indicate that a specific exonic SNP is associated with the disease, while using
      the separate reference class indicates that it is not associated, or vice versa.
      To address that, we introduce empirical Bayes methods that simultaneously
      consider a combined reference class and a separate reference class. Our
      simulation studies indicate that the proposed methods lead to improved
      performance. The new maximum entropy method achieves that by depending on the
      separate class when it has enough SNPs for reliable LFDR estimation and depending
      solely on the combined class otherwise. We used the new methods to analyze data
      from a GWAS of 2000 cases and 3000 controls. R functions implementing the
      proposed methods are available on CRAN https://cran.r
      project.org/web/packages/LFDREmpiricalBayes and Shiny
      https://empiricalbayes.shinyapps.io/lfdrempiricalbayesapp.

PMID- 30113899
TI  - Artificial Fish Swarm Optimization Based Method to Identify Essential Proteins.
AB  - It is well known that essential proteins play an extremely important role in
      controlling cellular activities in living organisms. Identifying essential
      proteins from protein protein interaction (PPI) networks is conducive to the
      understanding of cellular functions and molecular mechanisms. Hitherto, many
      essential proteins detection methods have been proposed. Nevertheless, those
      existing identification methods are not satisfactory because of low efficiency
      and low sensitivity to noisy data. This paper presents a novel computational
      approach based on artificial fish swarm optimization for essential proteins
      prediction in PPI networks (called AFSO_EP). In AFSO_EP, firstly, a part of known
      essential proteins are randomly chosen as artificial fishes of priori knowledge.
      Then, detecting essential proteins by imitating four principal biological
      behaviors of artificial fishes when searching for food or companions, including
      foraging behavior, following behavior, swarming behavior and random behavior, in
      which process, the network topology, gene expression, gene ontology (GO)
      annotation and subcellular localization information are utilized. To evaluate the
      performance of AFSO_EP, we conduct experiments on two species (Saccharomyces
      cerevisiae and Drosophila melanogaster), the experimental results show that our
      method AFSO_EP achieves a better performance for identifying essential proteins
      in comparison with several other well-known identification methods, which
      confirms the effectiveness of AFSO_EP.

PMID- 30113900
TI  - Feasibility of Self-powering and Energy Harvesting using Cardiac Valvular
      Perturbations.
AB  - In this paper we investigate the feasibility of harvesting energy from cardiac
      valvular perturbations to self-power a wireless sonomicrometry sensor. Compared
      to the previous studies involving piezoelectric patches or encasings attached to
      the cardiac or aortic surface, the proposed study explores the use of
      piezoelectric sutures that can be implanted in proximity to the valvular regions,
      where non-linear valvular perturbations could be exploited for self-powering.
      Using an ovine animal model, the magnitude of valvular perturbations are first
      measured using an array of sonomicrometry crystals implanted around the tricuspid
      valve. These measurements were then used to estimate the levels of electrical
      energy that could be harvested using a simplified piezoelectric suture model.
      These results were re-validated across seven different animals, before and after
      valve regurgitation was induced. Our study shows that power harvested from
      different annular planes of the tricuspid valve (before and after regurgitation)
      could range from nano-watts to milli-watts, with the maximum power harvested from
      the leaflet plane. We believe that these results could be useful for determining
      optimal surgical placement of wireless and self-powered sonomicrometry sensor,
      which in turn could be used for investigating the pathophysiology of ischemic
      regurgitation (IR).

PMID- 30113901
TI  - Highly Integrated FPGA-only Signal Digitization Method Using Single-ended Memory
      Interface Input Receivers for Time-of-Flight PET Detectors.
AB  - We propose a new highly integrated FPGA-only signal digitization method for
      individual signal digitization of time-of-flight positron emission tomography
      (TOF PET). We configured I/O port of the FPGA with a single-ended memory
      interface (SeMI) input receiver. The SeMI is a single-ended voltage-referenced
      interface that has a common reference voltage per I/O Bank, such that each SeMI
      input receiver can serve as a voltage comparator. The FPGA-only digitizer that
      uses the single-ended input receivers does not require a separate digitizing
      integrated chip, and can obtain twice as many signals as that using LVDS input
      receivers. We implemented a highly integrated digitizer consisting of 82 energy
      and 82 timing channels using a 28-nm FPGA. The energy and arrival time were
      measured using a 625-ps binary counter, and a 10-ps TDC, respectively. We first
      measured the intrinsic characteristics of the proposed FPGA-only digitizer. The
      SeMI input receiver functioned as the voltage comparator without undesirable
      offset voltage. The standard deviation value of the time difference measured
      using two SeMI input receivers with respective TDCs was less than 14.6 ps RMS. In
      addition, we fed signals from the TOF PET detectors to the SeMI input receivers
      directly and collected data. The TOF PET detector consisted of a 3*3*20 mm3 LYSO
      crystal coupled with a silicon photomultiplier. The energy resolutions were 7.7%
      and 7.1% for two TOF PET detectors. The coincidence resolving time was 204 ps
      FWHM. The SeMI digitizer with a high-performance signal digitizer, processor, and
      high-speed transceivers provides a compact all-in-one data acquisition system.

PMID- 30113902
TI  - Anatomical Structure Segmentation in Ultrasound Volumes using Cross Frame Belief
      Propagating Iterative Random Walks.
AB  - Ultrasound (US) is a widely used as a low-cost alternative to computed tomography
      (CT) or magnetic resonance (MRI) and primarily for preliminary imaging. Since
      speckle intensity in US images is inherently stochastic, readers are often
      challenged in their ability to identify the pathological regions in a volume of a
      large number of images. This paper introduces a generalized approach for
      volumetric segmentation of structures in US images and volumes. We employ an
      iterative random walks (IRW) solver, random forest (RF) learning model, and a
      gradient vector flow (GVF) based inter-frame belief propagation technique for
      achieving cross-frame volumetric segmentation. At the start, a weak estimate the
      tissue structure is obtained using estimates of parameters of a statistical
      mechanics model of ultrasound tissue interaction. Ensemble learning of these
      parameters further using a random forest is used to initialize the segmentation
      pipeline. IRW is used for correcting the contour in various steps of the
      algorithm. Subsequently, a GVF based inter-frame belief propagation is applied to
      adjacent frames based on initialization of contour using information in the
      current frame to segment the complete volume by frame-wise processing. We have
      experimentally evaluated our approach using two different datasets. Intravascular
      Ultrasound (IVUS) segmentation was evaluated using 10 pullbacks acquired at 20
      MHz and thyroid ultrasound segmentation is evaluated on 16 volumes acquired at 11
      - 16 MHz. Our approach obtains a Jaccard score of 0.937 +/- 0.022 for IVUS
      segmentation and 0.908 +/- 0.028 for thyroid segmentation while processing each
      frame in 1.15 +/- 0.05 s for IVUS and in 1.23 +/- 0.27 s for thyroid segmentation
      without the need of any computing accelerators like GPUs.

PMID- 30113903
TI  - Convolutional Neural Network with Shape Prior Applied to Cardiac MRI
      Segmentation.
AB  - In this paper, we present a novel convolutional neural network (CNN) architecture
      to segment images from a series of short-axis cardiac magnetic resonance slices
      (CMRI). The proposed model is an extension of the U-net that embeds a cardiac
      shape prior and involves a loss function tailored to the cardiac anatomy. Our
      system takes as input raw MR images, requires no manual preprocessing or image
      cropping and is trained to segment the endocardium and epicardium of the left
      ventricle, the endocardium of the right ventricle, as well as the center of the
      left ventricle. With its multi-resolution grid architecture, the network learns
      both high and low-level features useful to register the shape prior as well as
      accurately localize the borders of the cardiac regions. Experimental results
      obtained on the ACDC-MICCAI 2017 dataset show that our model segments multi
      slices CMRI (left and right ventricle contours) in 0.17 second with an average
      Dice coefficient of 0.91 and an average 3D Hausdorff distance of 9.5 mm.

PMID- 30113904
TI  - Distributed Average Tracking for Lipschitz-Type of Nonlinear Dynamical Systems.
AB  - In this paper, a distributed average tracking (DAT) problem is studied for
      Lipschitz-type of nonlinear dynamical systems. The objective is to design DAT
      algorithms for locally interactive agents to track the average of multiple
      reference signals. Here, in both dynamics of agents and reference signals, there
      is a nonlinear term satisfying a Lipschitz-type condition. Three types of DAT
      algorithms are designed. First, based on state-dependent-gain design principles,
      a robust DAT algorithm is developed for solving DAT problems without requiring
      the same initial condition. Second, by using a gain adaption scheme, an adaptive
      DAT algorithm is designed to remove the requirement that global information, such
      as the eigenvalue of the Laplacian and the Lipschitz constant, is known to all
      agents. Third, to reduce chattering and make the algorithms easier to implement,
      a couple of continuous DAT algorithms based on time-varying or time-invariant
      boundary layers are designed, respectively, as a continuous approximation of the
      aforementioned discontinuous DAT algorithms. Finally, some simulation examples
      are presented to verify the proposed DAT algorithms.

PMID- 30113905
TI  - Adaptive Fault-Tolerant Consensus Protocols for Multiagent Systems With Directed
      Graphs.
AB  - This paper investigates the problem of adaptive fault-tolerant tracking control
      for the multiagent systems (MASs) under the time-varying actuator faults and
      bounded unknown control input of the leader. On the basis of the local state
      information of neighboring agents, an adaptive fault-tolerant control protocol,
      which consists of the adaptive estimation of faults, is constructed to compensate
      for the loss of actuator effectiveness in the leader-follower consensus of MASs.
      Moreover, the modification term in the adaptive estimation can avoid high
      frequency oscillations. It is shown that the tracking errors converge to a
      neighborhood around the origin in the presence of actuator faults, and the
      performance of the tracking problem is improved. Furthermore, the protocol is
      distributed in the sense that the coupling gains are independent. Finally, two
      examples are given to show the effectiveness of the proposed control protocol.

PMID- 30113906
TI  - Semi-Global Output Consensus for Discrete-Time Switching Networked Systems
      Subject to Input Saturation and External Disturbances.
AB  - The semi-global output consensus problem for multiagent systems depicted by
      discrete-time dynamics subject to external disturbances and input saturation over
      switching networks is investigated in this paper. Assume that only a small part
      of subsystems have directly received the output of the exosystem. The distributed
      consensus algorithms are proposed by adopting the low-gain state feedback and the
      modified algebraic Riccati equation. Then, the outputs of all subsystems can
      reach synchronization asymptotically with those of the exosystem by using the
      proposed consensus protocols on some preconditions. Both the connected switching
      networks and the jointly connected switching networks are considered for the semi
      global output consensus problem, respectively. Some numerical simulation results
      are shown to validate the theoretical analysis.

PMID- 30113907
TI  - Face Detection With Different Scales Based on Faster R-CNN.
AB  - In recent years, the application of deep learning based on deep convolutional
      neural networks has gained great success in face detection. However, one of the
      remaining open challenges is the detection of small-scaled faces. The depth of
      the convolutional network can cause the projected feature map for small faces to
      be quickly shrunk, and most detection approaches with scale invariant can hardly
      handle less than 15$x$15 pixel faces. To solve this problem, we propose a
      different scales face detector (DSFD) based on Faster R-CNN. The new network can
      improve the precision of face detection while performing as real-time a Faster R
      CNN. First, an efficient multitask region proposal network (RPN), combined with
      boosting face detection, is developed to obtain the human face ROI. Setting the
      ROI as a constraint, an anchor is inhomogeneously produced on the top feature map
      by the multitask RPN. A human face proposal is extracted through the anchor
      combined with facial landmarks. Then, a parallel-type Fast R-CNN network is
      proposed based on the proposal scale. According to the different percentages they
      cover on the images, the proposals are assigned to three corresponding Fast R-CNN
      networks. The three networks are separated through the proposal scales and differ
      from each other in the weight of feature map concatenation. A variety of
      strategies is introduced in our face detection network, including multitask
      learning, feature pyramid, and feature concatenation. Compared to state-of-the
      art face detection methods such as UnitBox, HyperFace, FastCNN, the proposed DSFD
      method achieves promising performance on popular benchmarks including FDDB, AFW,
      PASCAL faces, and WIDER FACE.

PMID- 30113908
TI  - Fabrication of high-performance MXene-based all-solid-state flexible
      microsupercapacitor based on a facile scratch method.
AB  - MXenes have emerged as promising electrode materials for microsupercapacitors
      (MSCs) owing to their high volumetric and areal capacitances. In addition to the
      development of novel electrode materials, fabrication of interdigital electrodes
      is another key to realize high-performance MSCs. Herein, we demonstrate the
      patterning of few-layered Ti3C2T x nanosheets on various substrates for MSCs by a
      facile, fast, and nearly zero-cost 'scratch' strategy. The fabricated Ti3C2T x 
      based all-solid-state MSC achieves a high areal capacitance of 25.5 mF cm-2,
      which benefits from the unique layered structure and high electrical conductivity
      of the electrode. The fabricated planar MSC also delivers good cycling stability
      and excellent flexibility. Moreover, our fabrication strategy can be readily
      extended to other composite films for MSCs and become potential micropower
      sources for miniaturized electronic devices.

PMID- 30113909
TI  - Rapid mineralization of methyl orange by nanocrystalline-assembled mesoporous
      Cu2O microspheres.
AB  - In this study, nanocrystalline-assembled mesoporous Cu2O microspheres (MCMs) with
      enhanced visible-light driven photocatalytic activity were synthesized by a
      facile one-step hydrothermal method. MCMs exhibit excellent visible-light driven
      photocatalytic activity with 85% removal of methyl orange (MO) (60% removal of
      total organic carbon (TOC)) in 40 min. The excellent photocatalytic performance
      is dependent on the specific morphology and excellent visible-light absorption
      ability. Interestingly, MCMs can efficiently remove MO with or without light. The
      amount and categories of active species were determined by electron paramagnetic
      resonance and photoluminance (PL). Reactive oxygen species (ROS) (mainly
      .[Formula: see text] and H2O2) and Cu (I) radicals are important in fading and
      further mineralization of MO. With the assistance of gas chromatography-mass
      spectrometer , TOC and x-ray photoelectron spectroscopy, the degradation pathways
      in light and dark conditions were analyzed. It has been proven that MO could be
      efficiently mineralized by ROS generated in light, while reaction in dark
      condition was more likely to be an efficient fading process.

PMID- 30113910
TI  - p-GaN/n-ZnO nanorods: the use of graphene nanosheets composites to increase
      charge separation in self-powered visible-blind UV photodetectors.
AB  - ZnO-based heterojunctions have found applications as self-powered ultraviolet
      photodetectors (PDs). However, high doping levels are not compatible with high
      mobility for metallic doped ZnO-based PDs so further development has been
      inhibited. This study demonstrates a method to increase the open-circuit voltage
      (V oc) that allows keeping a sufficiently high level of mobility of ZnO, using a
      ZnO nanorod/GaN heterojunction that incorporates graphene nanosheets as the
      active layer. These hybrid PDs have triple the value for V oc of PDs that have
      only pure ZnO and better exhibit photo-response characteristics. The results of
      surface Kelvin probe microscopy and x-ray photoelectron spectrometer show that
      the complex defects that occur because Zn interstitials form a shallow donor in
      ZnO are mainly responsible for the increase in the value of V oc. Using this
      functional nanostructure as an active layer represents a new method for the
      manufacture of high-performance self-powered PDs.

PMID- 30113911
TI  - Comparison of Treatment Rates of Depression After Stroke Versus Myocardial
      Infarction: A Systematic Review and Meta-Analysis of Observational Data.
AB  - OBJECTIVE: Depression after stroke and myocardial infarction (MI) is common but
      often assumed to be undertreated without reliable evidence being available. Thus,
      we aimed to determine treatment rates and investigate the application of
      guidelines in these conditions. METHODS: Databases MEDLINE, EMBASE, PsycInfo, Web
      of Science, CINAHL, and Scopus were systematically searched without language
      restriction from inception to June 30, 2017. Prospective observational studies
      with consecutive recruitment reporting any antidepressant treatment in adults
      with depression after stroke or MI were included. Random-effects models were used
      to calculate pooled estimates of treatment rates. RESULTS: Fifty-five studies
      reported 32 stroke cohorts (n = 8938; pooled frequency of depression = 34%, 95%
      confidence interval [CI] = 29%-38%) and 17 MI cohorts (n = 10,767; pooled
      frequency of depression = 24%, 95% CI = 20%-28%). In 29 stroke cohorts, 24% (95%
      CI = 20%-27%) of 2280 depressed people used antidepressant medication. In 15 MI
      cohorts, 14% (95% CI = 8%-19%) of 2381 depressed people used antidepressant
      medication indicating a lower treatment rate than in stroke. Two studies reported
      use of psychosocial interventions, indicating that less than 10% of participants
      were treated. CONCLUSIONS: Despite the high frequency of depression after stroke
      and MI and the existence of efficacious treatment strategies, people often remain
      untreated. Innovative strategies are needed to increase the use of effective
      antidepressive interventions in patients with cardiovascular disease.

PMID- 30113912
TI  - A minimally invasive (sinus tarsi) approach with percutaneous K-wires fixation
      for intra-articular calcaneal fractures in children.
AB  - The aim of this study was to analyze the management of displaced intra-articular
      calcaneal fractures in children at our pediatric orthopedic and to determine the
      results following open reduction via minimally invasive sinus tarsi approach and
      fixation with Kirschner wires (K-wires). Overall, 25 available cases of calcaneal
      fractures in children with mean age of 9.8 years were treated by open reduction
      from January 2010 to December 2015. All patients were followed up from 12 to 30
      months (mean: 19 months). Clinical functional outcomes were graded using the
      American Orthopedic Foot and Ankle Society hindfoot scores. Radiographic
      evaluation included measurement of the Bohler's angle and Gissane's angle of the
      calcaneus on the lateral view. All fractures healed within 3 months. According to
      the American Orthopedic Foot and Ankle Society foot scoring system, the mean
      scores of type II fractures were 92.7+/-2.1, type III 90.2+/-1.8, and type IV
      89.7+/-2.7 at the latest follow-up. The preoperative and postoperative Bohler's
      angles were 17.1 degrees +/-10.7 degrees  and 35.9 degrees +/-6.7 degrees  in
      Sanders type II fractures, 14.4 degrees +/-11.5 degrees  and 34.7 degrees +/-8.5
      degrees  in type III, 9.3 degrees +/-9.7 degrees  and 35.1 degrees +/-4.9 degrees
      in type IV, respectively. The preoperative and postoperative Gissane's angles
      were 102.6 degrees +/-11.5 degrees  and 125.7 degrees +/-7.8 degrees  in Sanders
      type II fractures, 101.7 degrees +/-9.1 degrees  and 117.5 degrees +/-10.8
      degrees  (P<0.05) in type III, and 104.7 degrees +/-5.1 degrees  and 122.8
      degrees +/-9.1 degrees  (P<0.05) in type IV, respectively. No secondary arthrosis
      has been observed so far. No deep infection and wound necrosis occurred. One
      patient had superficial infection around K-wires that was managed using
      dressings. Treatment of calcaneal fractures in children by open reduction by
      sinus tarsi approach and K-wires fixation is a safe and effective method with low
      incidence of complications.

PMID- 30113913
TI  - Novel Technologies Found to be Valid and Reliable for the Measurement of Vertical
      Jump Height With Jump-and-Reach Testing.
AB  - Brooks, ER, Benson, AC, and Bruce, LM. Novel technologies found to be valid and
      reliable for the measurement of vertical jump height with jump-and-reach testing.
      J Strength Cond Res 32(10): 2838-2845, 2018-Vertical jump testing is used by
      coaches and athletes across many sports and disciplines to assess lower-body
      power and neuromuscular fatigue. A range of devices are available to measure jump
      height, with recent innovations attempting to improve portability, usability, and
      accessibility. New devices should be evaluated for their effectiveness and
      dependability in specific tests before being adopted. The purpose of this study
      was to assess the validity and reliability of 2 novel measurement devices for
      jump height testing with a jump-and-reach protocol. Twenty-six healthy, active
      adults participated during 2 testing occasions. A wearable inertial measurement
      unit (VERT) and a smart device application (My Jump 2) were compared with
      established measures (force platform and jump-and-reach apparatus [Yardstick]).
      Correlations between the VERT and force platform were r = 0.95 (90% confidence
      interval [CI]: 0.93-0.97), and r = 0.93 (90% CI: 0.90-0.95) for the Yardstick.
      Correlations between the My Jump 2 app and force platform were r = 0.98 (90% CI:
      0.97-0.99), and r = 0.94 (90% CI: 0.92-0.96) for the Yardstick. Reliability,
      measured as intraclass correlation coefficient (ICC), was 0.91 (90% CI: 0.87
      0.94) for the VERT, and 0.97 (90% CI: 0.96-0.98) for the My Jump 2 app.
      Intrarater reliability for the My Jump 2 app was ICC = 0.99 (90% CI: 0.99-0.99).
      The VERT and the My Jump 2 app have both shown acceptable validity and
      reliability compared with both the force platform and Yardstick. However,
      practitioners should consider which measurement device/s to use based on the
      acceptable level of potential error for their population and testing objectives.

PMID- 30113914
TI  - Changes in External Load When Modifying Rules of 5-on-5 Scrimmage Situations in
      Elite Basketball.
AB  - Vazquez-Guerrero, J, Reche, X, Cos, F, Casamichana, D, and Sampaio, J. Changes in
      external load when modifying rules of 5-on- 5 scrimmage situations in elite
      basketball. J Strength Cond Res XX(X): 000-000, 2018-Constraining tasks are very
      frequent during the team sports training process; however, most of the effects of
      these coaching decisions are unknown, which leads to less controlled performing
      environments, with less chances to promote improvements. The aim of this study
      was to determine the effects of modifying rules of 5-a-side scrimmage on the
      physical performance of professional basketball players. Data were collected from
      12 elite male players (age, 29.6 +/- 4.5 years; height, 1.99 +/- 9.6 cm; body
      mass, 92.1 +/- 11.9 kg) from the Spanish first Division of Basketball during
      thirty-three 5-on-5 scrimmage situations over a 18-week period. Physical demands
      were assessed using WIMU PRO Local Positioning System (Realtrack Systems,
      Almeria, Spain) and included total and speed-ranged distance covered, player
      load, peak speed, number of high-intensity actions, number of total and high
      intensity accelerations and decelerations, and peak acceleration. A repeated
      measures analysis of variance was used to test the differences in all variables,
      considering playing in half-court (HALF), half-court and transition (HTRAN), and
      full-court (FULL) conditions for the 5-on-5 scrimmage drill. Results showed that
      during the HALF condition, there was less distance covered (effect size [ES] =
      3.55), lower peak speeds (ES = 3.00), less player load (ES = 2.79), lesser number
      of high-intensity actions (ES = 1.45), and lesser number of high-intensity
      accelerations (ES = 1.44) and decelerations (ES = 1.31) than in FULL. In HTRAN,
      players covered more distance (ES = 2.42), presented higher player load (ES =
      1.88), higher intensity actions (ES = 1.02), and peak speed (ES = 4.22) than in
      HALF. In conclusion, physical demands can be modulated changing the rules and
      court size using 5-on-5 scrimmage situations, and this factor should be taken
      into account when designing training drills and when fine-tuning periodization.

PMID- 30113915
TI  - Effects of Accentuated Eccentric Loading on Muscle Properties, Strength, Power,
      and Speed in Resistance-Trained Rugby Players.
AB  - Douglas, J, Pearson, S, Ross, A, and McGuigan, M. Effects of accentuated
      eccentric loading on muscle properties, strength, power, and speed in resistance
      trained rugby players. J Strength Cond Res 32(10): 2750-2761, 2018-The purpose of
      this study was to determine the effects of slow and fast tempo resistance
      training incorporating accentuated eccentric loading (AEL) compared with
      traditional resistance training (TRT) in trained rugby players. Fourteen subjects
      (19.4 +/- 0.8 years, 1.82 +/- 0.05 m, 97.0 +/- 11.6 kg, and relative back squat 1
      repetition maximum [1RM]: 1.71 +/- 0.24 kg.BM) completed either AEL (n = 7) or
      TRT (n = 7) strength and power protocols. Two 4-week phases of training were
      completed. The first phase emphasized a slow eccentric tempo, and the second
      phase emphasized a fast eccentric tempo. Back squat 1RM, inertial load peak
      power, drop jump reactive strength index (RSI), 40-m speed, maximum sprinting
      velocity (Vmax), and vastus lateralis (VL) muscle architectural variables were
      determined at baseline and after each phase of training. Slow AEL elicited
      superior improvements in back squat 1RM (+0.12 kg.BM; effect size [ES]: 0.48; and
      90% confidence interval [CI]: 0.14, 0.82), 40-m time (-0.07 seconds; ES: 0.28;
      and CI: 0.01-0.55), and Vmax (+0.20 m.s; ES: 0.52; and CI: 0.18-0.86) vs. slow
      TRT. Fast AEL elicited a small increase in RSI but impaired speed. There was a
      likely greater increase in peak power with fast TRT (+0.72 W.kg; ES: 0.40; and
      CI: 0.00-0.79) vs. fast AEL alongside a small increase in VL pennation angle. The
      short-term incorporation of slow AEL was superior to TRT in improving strength
      and maximum velocity sprinting speed in rugby players undertaking a concurrent
      preparatory program. The second 4-week phase of fast AEL may have exceeded
      recovery capabilities compared with fast TRT.

PMID- 30113916
TI  - Practical Considerations for Assessing Pulmonary Gas Exchange and Ventilation
      During Flume Swimming Using the MetaSwim Metabolic Cart.
AB  - Lomax, M, Mayger, B, Saynor, ZL, Vine, C, and Massey, HC. Practical
      considerations for assessing pulmonary gas exchange and ventilation during flume
      swimming using the MetaSwim metabolic cart. J Strength Cond Res XX(X): 000-000,
      2018-The MetaSwim (MS) metabolic cart can assess pulmonary gas exchange and
      ventilation in aquatic environments. The aims of this study were: (a) to
      determine the agreement between minute ventilation (V[Combining Dot Above]E),
      pulmonary oxygen uptake (V[Combining Dot Above]O2), and carbon dioxide output
      (V[Combining Dot Above]CO2) using the MS and Douglas bag (DB) methods during
      flume swimming; and (b) to assess the repeatability of these and other MS-derived
      parameters. Sixteen trained swimmers completed a combined incremental and
      supramaximal verification cardiopulmonary swimming test to determine maximal
      V[Combining Dot Above]O2, 2 progressive intensity swimming tests during which MS
      and DB measurements were made (agreement protocol), and 3-4 constant-velocity
      submaximal swimming tests during which only the MS was used (repeatability
      protocol). Agreement was determined using limits of agreement (LoA), bias, random
      error, and 95% confidence intervals with systematic bias assessed using paired
      samples t-tests. Within-trial and between-trial repeatability were determined
      using the coefficient of variation (CV) and the repeatability coefficient (CR).
      Where data were heteroscedastic, LoA and CR were log-transformed, antilogged, and
      displayed as ratios. MetaSwim underestimated peak V[Combining Dot Above]O2 and
      V[Combining Dot Above]CO2 (<=0.39 L.min) and V[Combining Dot Above]E (9.08
      L.min), whereas submaximal values varied between 2 and 5% for CV and +/-1.09-1.22
      for ratio CR. The test-retest CV during constant-velocity swimming for
      V[Combining Dot Above]E, tidal volume, breathing frequency, V[Combining Dot
      Above]O2, V[Combining Dot Above]CO2, and end-tidal pressures of O2 and CO2 was
      <9% (ratio CR of +/-1.09-1.34). Thus, the MS and DB cannot be used
      interchangeably. Whether the MS is suitable for evaluating ventilatory and
      pulmonary responses in swimming will depend on the size of effect required.

PMID- 30113917
TI  - Monitoring Age-Group Swimmers Over a Training Macrocycle: Energetics, Technique,
      and Anthropometrics.
AB  - Zacca, R, Azevedo, R, Chainok, P, Vilas-Boas, JP, Castro, FAdS, Pyne, DB, and
      Fernandes, RJ. Monitoring age-group swimmers over a training macrocycle:
      energetics, technique, and anthropometrics. J Strength Cond Res XX(X): 000-000,
      2018-The aim of this study was to quantify changes and contributions of
      energetic, technique, and anthropometric profiles across the first training
      macrocycle (16-week) in a traditional 3-peak swimming season. Twenty-four age
      group swimmers (10 boys and 14 girls age 14.4 +/- 0.9 years) of equal
      maturational stage were monitored through a 400-m test in front crawl (T400).
      Energetic, technique, and anthropometric characteristics were compared before
      (experimental testing 1, E1) and after the preparatory (E2), specific (E3), and
      competitive (E4) training periods. Sex interaction was not significant for any
      variable. Multiple linear regressions and principal component analysis were used
      to identify the most influential variables and the relative contribution of each
      domain (energetics, technique, and anthropometrics) to changes in swimming
      performance of T400. The relative contributions for performance of T400 at E1,
      E2, E3, and E4 were 15, 12, 6, and 13% for energetics, 78, 85, 75, and 70% for
      technique, and 7, 3, 19 and 17% for anthropometrics, respectively. Technique
      played the main role during the first 16-week macrocycle in a competitive season,
      regardless of small fluctuations in the influence of energetics and
      anthropometrics. Changes and influence of energetics, technique, and
      anthropometric on age-group swimmers' performance could be described by the T400
      swimming test, providing a comprehensive biophysical overview of the main
      contributors to swimming performance.

PMID- 30113918
TI  - Influence of Workload and Recovery on Injuries in Elite Male Volleyball Players.
AB  - Timoteo, TF, Debien, PB, Miloski, B, Werneck, FZ, Gabbett, T, and Filho, MGb.
      Influence of workload and recovery on injuries in elite male volleyball players.
      J Strength Cond Res XX(X): 000-000, 2018-The aim of this study was to investigate
      the influence of workload and recovery on injury rates in elite male volleyball
      players. Data were collected from 14 male professional volleyball players over a
      27-week season. Workloads were monitored daily using the session rating of
      perceived exertion, and recovery status was appraised using the Total Quality
      Recovery (TQR) scale. The players were exposed to 4,573.31 hours (h) of training
      and games with an overall injury incidence of 13.99 per 1,000 hours. Overuse
      accounted for 83% (11.58 injuries/1,000 hours) and trauma accounted for 17% (2.40
      injuries per 1,000 hours) of all injuries. There was a higher incidence of
      injuries (p = 0.003), higher weekly workload (p = 0.008), and acute:chronic
      workload ratio (ACWR) (p < 0.001) in the pre-season compared with the competitive
      period. Healthy players had lower ACWR (p = 0.002) compared with the injured
      players. The TQR was higher for the healthy group compared with the injured group
      (p < 0.001). The greater odds of injury was related to higher ACWR (risk factor)
      (p = 0.014) and lower TQR values (p = 0.004) (protection factor). Athlete's
      workloads and the state of recovery may be related to injuries in volleyball. The
      results presented in this study emphasize the importance of controlling these
      variables in professional volleyball teams to prevent injuries.

PMID- 30113920
TI  - Effects of High-Intensity Interval Training vs. On-Court Tennis Training in Young
      Tennis Players.
AB  - Kilit, B and Arslan, E. Effects of high-intensity interval training vs. on-court
      tennis training in young tennis players. J Strength Cond Res XX(X): 000-000, 2018
      This study aimed to examine the effects of 6 weeks of high-intensity interval
      training (HIIT) vs. 6 weeks of on-court tennis training (OTT) on the
      psychophysiological responses, performance responses, and technical scores of
      young tennis players. Twenty-nine young male tennis players (aged 13.8 +/- 0.4
      years) were divided into HIIT (n = 14) and OTT groups (n = 15). Both groups
      trained for the same total training duration with passive rest in each session.
      Pre-test and post-test included maximum oxygen consumption (V[Combining Dot
      Above]O2max), sprinting, jumping, 400-m running time, a tennis-specific technical
      test, and the t-drill agility test. The training interventions resulted in
      similar improvements in V[Combining Dot Above]O2max responses (HIIT: +5.2%, d =
      1.36 [large effect]; OTT: +5.5%, d = 1.50 [large effect]). Both training
      protocols increased jumping and sprinting performances significantly from pre
      testing to post-testing (p < 0.05, d values ranging from 0.40 to 1.10). The OTT
      group showed significantly higher performance responses in terms of the agility
      test performance and technical scores (p < 0.05, d = ranging from 0.77 to 0.88
      [moderate effect]) compared with the HIIT group. By contrast, the HIIT group
      exhibited significantly higher performance responses in terms of the 400-m
      running time (p < 0.05, d = 1.32 [large effect]). Our results showed that tennis
      specific on-court drills might be a more effective training strategy to improve
      agility and technical ability with greater physical enjoyment, whereas HIIT may
      be more appropriate for speed-based conditioning in young tennis players.

PMID- 30113919
TI  - Effects of Far-Infrared Emitting Ceramic Materials on Recovery During 2-Week
      Preseason of Elite Futsal Players.
AB  - Nunes, RFH, Cidral-Filho, FJ, Flores, LJF, Nakamura, FY, Rodriguez, HFM,
      Bobinski, F, De Sousa, A, Petronilho, F, Danielski, LG, Martins, MM, Martins, DF,
      and Guglielmo, LGA. Effects of far-infrared emitting ceramic materials on
      recovery during 2-week preseason of elite futsal players. J Strength Cond Res
      XX(X): 000-000, 2018-We investigated the effects of far-infrared emitting ceramic
      materials (cFIR) during overnight sleep on neuromuscular, biochemical and
      perceptual markers in futsal players. Twenty athletes performed a 2-week
      preseason training program and during sleep wore bioceramic (BIO; n = 10) or
      placebo pants (PL; n = 10). Performance (countermovement jump [CMJ]; squat jump
      [SJ]; sprints 5, 10, and 15-m) and biochemical markers (tumor necrosis factor
      alpha-TNF-alpha, interleukin 10-IL-10, thiobarbituric acid-reactive species
      [TBARS], carbonyl, superoxide dismutase [SOD], catalase [CAT]) were obtained at
      baseline and after the 1st and 2nd week of training. Delayed-onset muscle
      soreness (DOMS) and training strain were monitored throughout. Changes in
      DeltaCMJ and DeltaSJ were possibly (60/36/4 [week-1]) and likely (76/22/2 [week
      2]) higher in BIO. Both groups were faster in 5-m sprint in week 2 compared with
      baseline (p = 0.015), furthermore, BIO was likely faster in 10-m sprint (3/25/72
      [week 1]). Significant group * time interaction in %DeltaTNF-alpha were observed
      (p = 0.024 [week-1]; p = 0.021 [week-2]) with values possibly (53/44/3 [week 1])
      and likely (80/19/1 [week 2]) higher in BIO. The %DeltaIL-10 decreased across
      weeks compared with baseline (p = 0.019 [week-1]; p = 0.026 [week-2]), showing
      values likely higher in BIO (81/16/3 [week-1]; 80/17/3 [week-2]). Significant
      weekly increases in %DeltaTBARS (p = 0.001 [week-1]; p = 0.011 [week-2]) and
      %DeltaCarbonyl (p = 0.002 [week-1]; p < 0.001 [week-2]) were observed compared
      with baseline, showing likely (91/5/4 [week-1]) and possibly (68/30/2 [week-2])
      higher changes in BIO. Significant weekly decreases in %DeltaSOD were observed
      compared with baseline (p = 0.046 [week 1]; p = 0.011 [week-2]), and between week
      2 and week 1 (p = 0.021), in addition to significant decreases in %DeltaCAT
      compared with baseline (p = 0.070 [week 1]; p = 0.012 [week 2]). Training strain
      (p = 0.021; very -likely [0/2/98]; week 1) and DOMS was lower in BIO (likely; 7
      sessions) with differences over time (p = 0.001). The results suggest that the
      daily use of cFIR clothing could facilitate recovery, especially on perceptual
      markers during the early phases of an intensive training period.

PMID- 30113921
TI  - Abnormal intrinsic brain activity in individuals with peripheral vision loss
      because of retinitis pigmentosa using amplitude of low-frequency fluctuations.
AB  - The study aimed to determine alterations in intrinsic brain activity in retinitis
      pigmentosa (RP) individuals using the amplitude of low-frequency fluctuation
      (ALFF)/fractional amplitude of low-frequency fluctuation (fALFF) method. Sixteen
      RP individuals (10 men and six women) and 14 healthy controls (HCs) (six men and
      eight women) closely matched in age, sex, and education were enrolled in the
      study. The ALFF/fALFF method was applied to compare different intrinsic brain
      activities between the RP group and the HC group. The relationship between the
      mean ALFF/fALFF signal values of different brain regions and the visual
      measurements in RP group was analyzed by Pearson correlation. Compared with HCs,
      RP individuals had significantly lower ALFF values in the bilateral lingual gyrus
      (LIGG)/cerebellum posterior lobe [Brodmann area (BA) 17,18], but lower fALFF
      values in the bilateral LIGG/cerebellum anterior lobe (BA 17,18). Meanwhile, RP
      individuals had significantly higher ALFF in the bilateral precuneus
      cortex/middle cingulate cortex (BA 7,31), as well as higher fALFF values in the
      left superior/middle frontal gyrus (BA 9,10) and bilateral supplementary motor
      area (BA 6,8) (voxel-level P<0.01, cluster-level P<0.05). Moreover, the fALFF
      values of the bilateral LIGG/cerebellum anterior lobe showed positive
      relationships with the best-corrected visual acuity (BCVA)-oculus dexter
      (r=0.574, P=0.020) and BCVA-oculus sinister (r=0.570, P=0.021) in RP individuals;
      our results provide evidence that RP individuals may have impaired intrinsic
      brain activity in the primary visual area and the visuomotor coordination area
      that correlates with BCVA. Moreover, our findings indicate that reorganization of
      the dorsal visual stream and the parietoprefrontal pathway occurs in RP
      individuals.

PMID- 30113922
TI  - PI3K/AKT/GSK3beta/CRMP-2-mediated neuroplasticity in depression induced by
      stress.
AB  - Early neurodevelopmental dysplasia or disorder is an important stimulus for
      depression, but early stress can easily damage nerve development and lead to
      decreased neural plasticity. Because of the characteristics of nerve cell, nerve
      loop, structure instability and so on, stress can often lead to the occurrence
      and recurrence of depression. Stress is often associated with the release of
      inflammatory factors in the central nervous system. Recent studies suggest that
      neuroinflammatory factors are most likely involved in the occurrence and
      development of stress-induced depression, attacking neuronal cells through
      central inflammatory factors. The changes in neural plasticity, such as
      microtubule system of nerve scaffold, extension of axonal dendrites, regeneration
      of nerve junctions, disturbance of neurotransmitter synthesis, transmission and
      release, and abnormal synapses, cause abnormal transmission of information
      between nerve cells and cause symptoms of depression. The changes in the
      structure of neural stent microtubules are closely related to the neuroplastic
      damage of depression induced by stress. Our previous studies and current studies
      have found that the AKT/GSK3beta/CRMP-2 pathway mediates the changes in neural
      stent microtubule plasticity. There is an interaction between central
      inflammatory factors and this pathway. Therefore, from the point of view of
      neuritis injury and the plasticity change of nerve scaffold, it can be concluded
      that after the activation and release of central inflammatory factor under
      stress, the possible mechanism of depression is mediated by the AKT/GSK3beta/CRMP
      2 pathway by changing the normal structure and function of the central nervous
      cell scaffold microtubule system.

PMID- 30113923
TI  - Symmetric tract-based spatial statistics of patients with left versus right
      mesial temporal lobe epilepsy with hippocampal sclerosis.
AB  - This study aims to investigate the diffusion metrics of left versus right
      temporal lobe epilepsy in a well-defined subgroup of patients with mesial
      temporal lobe epilepsy (mTLE) because of unilateral hippocampal sclerosis while
      taking into account interhemispheric differences. Eighteen patients with TLE
      [nine left temporal lobe epilepsy (LTLE) and nine right temporal lobe epilepsy
      (RTLE)] and a norm group of 36 nonepileptic individuals were scanned with a
      multiband accelerated diffusion tensor imaging protocol at 3T. The scalar
      diffusion tensor parameters fractional anisotropy (FA), mean diffusivity (MD),
      and radial diffusivity (RD) and, after projection on a symmetric skeleton, their
      hemispheric difference (dFA, dMD, and dRD) were analyzed using tract-based
      spatial statistics. In the cluster with significantly (P<0.008) different dFA,
      dMD, and dRD between right TLE and left TLE, the hemispheric difference in the
      mean scalar indices (dmFA, dmMD, and dmRD) was assessed and tested for
      differences using a one-way analysis of variance and for correlation with patient
      age, seizure onset, or duration of epilepsy using Pearson's correlation. Patients
      with LTLE showed lower dFA, higher dMD, and higher dRD (P<0.008) compared with
      patients with RTLE in a cluster including parts of the uncinated and inferior
      longitudinal fasciculus and the inferior fronto-occipital fasciculus. dmFA, dmMD,
      and dmRD differed significantly between groups (P<10, corrected) and showed no
      correlation with patient age, seizure onset, or duration of epilepsy. The
      exclusion of bilateral interindividual variance through the calculation of the
      hemispheric difference of the diffusion metrics by the symmetric variant of tract
      based spatial statistics allows for a sensitive differentiation of LTLE and RTLE
      with unilateral hippocampal sclerosis.

PMID- 30113924
TI  - CE: Managing Stable COPD: An Evidence-Based Approach.
AB  - : Chronic obstructive pulmonary disease (COPD) affects as many as 16 million
      Americans and is expected to be the third leading cause of death worldwide by
      2020. To increase awareness of COPD, encourage related research, and improve care
      of patients with this chronic disease, the Global Initiative for Chronic
      Obstructive Lung Disease (GOLD) was launched in 1998 and published an evidence
      based report on COPD prevention and management strategies in 2001 that has been
      revised regularly. The fourth major revision, which was published in 2017 and
      revised in 2018, includes significant changes related to COPD classification, as
      well as to pharmacologic, nonpharmacologic, and comorbidity management. The
      authors discuss the changes to the GOLD recommendations and, using a patient
      scenario, explain their application to clinical practice.

PMID- 30113925
TI  - CE: Too Much Sitting: A Newly Recognized Health Risk.
AB  - : While moderate-to-vigorous physical activity (MVPA) has been widely accepted as
      a major factor in promoting optimal health, emerging research specific to
      sedentary behavior suggests that MVPA alone may not be enough. This integrative
      literature review examines the evidence on sedentary behavior as an independent
      health risk for cardiometabolic health conditions, certain cancers, and all-cause
      mortality. In so doing, it reveals new insights into high-volume sitting and
      prolonged uninterrupted sitting and their relationship to adverse health
      conditions in order to increase awareness of sedentary behavior as an independent
      health risk factor, examine the potential effects of displacing sedentary time
      with light-intensity physical activity, and encourage nurses to advance the
      overall reduction of sedentary behavior.

PMID- 30113926
TI  - Analysis of survival and prognostic factors in treatment of hepatocellular
      carcinoma in Spanish patients with drug-eluting bead transarterial
      chemoembolization.
AB  - BACKGROUND AND AIM: Drug-eluting bead transarterial chemoembolization (DEB-TACE)
      improves the survival of patients with hepatocellular carcinoma (HCC),
      intermediate stage [i.e. Barcelona Clinic Liver Cancer-B (BCLC-B)]. The aim of
      our study was to analyse the overall survival (OS) and prognostic factors of
      patients with HCC treated with DEB-TACE. PATIENTS AND METHODS: Patients' clinical
      course was recorded from January 2005 to July 2014. The median OS was obtained by
      the Kaplan-Meier method and compared using the log-rank test. The prognosis
      factors associated with OS were determined by a multivariate Cox regression
      analysis and the accuracy of the OS prediction was determined by calculation of
      the assessment for retreatment with TACE score (ART score). RESULTS: A cohort of
      147 consecutive patients treated with DEB-TACE was included. Median age of the
      patients was 73.4 years. Overall, 68.7% were men, and all had cirrhosis, with
      68.8% being hepatisis C virus positive. Moreover, 35.2% were staged as BCLC-A and
      60.2% as BCLC-B. After a median follow-up of 19.2 months, 29.3% were alive, 4.3%
      needed treatment with sorafenib and 56.1% underwent DEB-TACE retreatment. Median
      OS was 22.8 [95% confidence interval (CI)=19.6-25.9]. After censoring for ascites
      and more than one nodule, OS was 23.87 (95% CI =20.72-27.01) and 26.89 (95% CI
      =21.00-32.78), respectively. The risk of death decreased by 22.3% with the number
      of DEB-TACE sessions (hazard ratio=0.777) and increased by 25.9% with higher
      Child-Pugh score (hazard ratio=1.259). Overall, 61.2% of the cohort had an ART
      score between 0 and 1.5. There were no statistical differences in OS between
      cohort groups with ART of 0-1.5 and at least 2.5. CONCLUSION: The results
      validate the efficacy and safety of DEB-TACE in patients with HCC and the
      importance of some prognostic factors for patient survival.

PMID- 30113927
TI  - Mutation of PACS1: the milder end of the spectrum.

PMID- 30113929
TI  - Monitoring of Metabolic, Cardiac, and Endocrine Indicators in Youth Treated With
      Antipsychotics as Reported by Health Care Professionals.
AB  - BACKGROUND: It is unclear how youth treated with antipsychotics are monitored.
      The purpose of this study was to assess monitoring of metabolic, cardiac, and
      endocrine indicators in youth (<18 years old) treated with antipsychotics as
      reported by health care professionals in the Netherlands. METHODS: A
      questionnaire was designed to collect information from health care professionals
      regarding the monitoring of youth treated with antipsychotics. Data were
      collected at a national conference. FINDINGS AND RESULTS: Fifty-nine health care
      professionals completed the questionnaire, of which 53 (89.8%) were child and
      adolescent psychiatrists (approximately 20% of all child and adolescent
      psychiatrists in the Netherlands). More than 80% of respondents reported
      monitoring physical indicators-weight, height, body mass index, heart rate, and
      blood pressure-and over 50% reported monitoring laboratory indicators-lipid
      profile, blood glucose, and prolactin level. Most of the respondents reported
      monitoring physical indicators more than twice per year and laboratory indicators
      once per year. Almost all respondents (56/59, 94.9%) reported monitoring
      according to a clinical guideline or protocol. Only 1 respondent reported
      monitoring the indicators completely according to the clinical guideline.
      Respondents mentioned that facilitating factors for monitoring, such as access to
      electrocardiogram facilities, were insufficiently available. CONCLUSIONS:
      Although all health care professionals reported monitoring metabolic, cardiac,
      and endocrine indicators in youth treated with antipsychotics, great variability
      exists in reported monitoring practices. Factors contributing to this variability
      must be assessed to optimize the benefit-risk ratio for the individual patient.

PMID- 30113928
TI  - Optimal treatment for obsessive compulsive disorder: a randomized controlled
      feasibility study of the clinical-effectiveness and cost-effectiveness of
      cognitive-behavioural therapy, selective serotonin reuptake inhibitors and their
      combination in the management of obsessive compulsive disorder.
AB  - Established treatments for obsessive compulsive disorder (OCD) include cognitive
      behaviour therapy (CBT) and selective serotonin reuptake inhibitor (SSRI)
      medication. Combined treatment may outperform monotherapy, but few studies have
      investigated this. A total of 49 community-based adults with OCD were randomly
      assigned to CBT, SSRI, or SSRI+CBT. Sertraline (50-200 mg/day) was given as the
      SSRI for 52 weeks. A 16-h-manualized individual CBT was delivered over 8 weeks
      with four follow-up sessions. Assessors were 'blinded' to treatment allocation. A
      preliminary health economic evaluation was conducted. At week 16, combined
      treatment (n=13) was associated with the largest improvement, sertraline (n=7)
      the next largest and CBT (n=9) the smallest on the observed case analysis. The
      effect size (Cohen's d) comparing the improvement in Yale Brown Obsessive
      Compulsive Scale on CBT versus combined treatment was -0.39 and versus sertraline
      was -0.27. Between 16 and 52 weeks, the greatest clinical improvement was seen
      with sertraline, but participant discontinuation prevented reliable analysis.
      Compared with sertraline, the mean costs were higher for CBT and for combined
      treatment. The mean Quality Adjusted Life Year scores for sertraline were 0.1823
      (95% confidence interval: 0.0447-0.3199) greater than for CBT and 0.1135 (95%
      confidence interval: -0.0290-0.2560), greater than for combined treatment.
      Combined treatment appeared the most clinically effective option, especially over
      CBT, but the advantages over SSRI monotherapy were not sustained beyond 16 weeks.
      SSRI monotherapy was the most cost-effective. A definitive study can and should
      be conducted.

PMID- 30113930
TI  - Zero Eosinophil Count as a Predictor of Clozapine-Associated Late-Onset
      Agranulocytosis: A Case Report.

PMID- 30113931
TI  - Statistics Commentary Series: Commentary No. 28: Statistical Significance and
      Replication.

PMID- 30113932
TI  - Long-term Challenges After Solid Organ Transplantation: Summary of Expert
      Presentations From the Sandoz 5th Standalone Transplantation Meeting, 2017.

PMID- 30113933
TI  - SUPRACHOROIDAL INJECTION OF TRIAMCINOLONE ACETONIDE, CLS-TA, FOR MACULAR EDEMA
      DUE TO NONINFECTIOUS UVEITIS: A Randomized, Phase 2 Study (DOGWOOD).
AB  - PURPOSE: Evaluate a single suprachoroidal injection of a proprietary
      triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to
      noninfectious uveitis. METHODS: Randomized, controlled, masked Phase 2 study.
      Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8
      mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary
      efficacy endpoint was change in central subfield thickness from baseline to Month
      2, assessed by spectral domain optical coherence tomography. RESULTS: Twenty-two
      adults were enrolled. The primary endpoint was met in subjects who received
      suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness
      significantly decreased from baseline by 135 um and 164 um at Month 1 (P =
      0.0056) and Month 2 (P = 0.0017), respectively. At Month 2, 69% of subjects who
      received 4.0 mg experienced >=20% reduction in central subfield thickness, and
      65% had improvement of best-corrected visual acuity of >=5 Early Treatment
      Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters (P =
      0.0004). Safety analyses supported acceptable safety/tolerability, with no
      corticosteroid-related increases in intraocular pressure. CONCLUSION: A single
      suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular
      edema due to noninfectious uveitis was well-tolerated, significantly reduced
      central subfield thickness from baseline at 2 months, and significantly improved
      visual acuity.

PMID- 30113934
TI  - Radiation-Induced Optic Neuropathy: Clinical and Imaging Profile of Twelve
      Patients.
AB  - BACKGROUND: Radiation-induced optic neuropathy (RON) is a form of delayed
      radionecrosis of the anterior visual pathways, which develops within months to
      years after external cranial irradiation and causes severe and irreversible
      vision loss. Small series reports have adequately documented its clinical
      features, but imaging characteristics have been less completely described.
      METHODS: We accrued cases from the University of Michigan Neuro-Ophthalmology
      Clinic files and from cases coded as "radiation optic neuropathy" at the
      University of Michigan Medical Center between 1994 and 2017. All patients had
      undergone 3D-conformal linear accelerator (photon) external beam radiation. We
      collected clinical details of vision loss, including the temporal relationship to
      radiation. A single neuroradiologist (E.A.L.) evaluated all available magnetic
      resonance imaging (MRI) studies, noting the presence of enhancement, expansion,
      or volume loss of the optic nerves or chiasm, corresponding T2 signal
      abnormalities, and the absence of demyelination or confounding compressive
      lesions. RESULTS: Twelve patients (15 eyes) met inclusion criteria. Vision loss
      was usually monocular at outset, but both optic nerves were eventually involved
      in 3 (25%) patients. Although usually sudden in onset, vision loss often declined
      slowly over many months, frequently to finger counting, or worse without
      recovery. An afferent pupillary defect was always present at the time of
      presentation. Most affected optic discs were pale at the time of first visual
      symptoms, indicating that subclinical optic nerve damage had been present for
      several weeks. The latency from completion of radiation to onset of vision loss
      ranged from 7 to 48 months (average: 18 months). In 2 patients, radiation was
      delivered to the whole brain, rather than being limited to the anterior visual
      pathway. MRI typically displayed a discrete region of enhancement of the affected
      prechiasmatic optic nerve, often with expansion and high T2 signal in the
      enhancing segment. In 3 affected eyes, enhancement was apparent on imaging
      completed 3-6 weeks before the onset of vision loss. In one patient, segmental
      prechiasmatic enhancement became evident only on repeat MRI completed 7 months
      after vision loss. The duration of enhancement among 9 eyes with follow-up MRIs
      was at least 2 months, but in one case, enhancement was still present on a study
      performed 17 months after treatment. CONCLUSIONS: This study further delineates
      the profile of RON. Visual loss is often acute, profound, and monocular but may
      decline slowly after acute onset and later affect both optic nerves. High
      resolution MRI of the optic nerves usually will display enhancement of a discrete
      segment of the intracranial prechiasmatic optic nerve, often with accompanying
      expansion and T2 hyperintensity. In some cases, these imaging features may
      precede vision loss. They may be subtle or appear after vision loss. Enhancement
      lingers for a wide interval, ranging in this study from 2 to at least 17 months.
      Recognition of these imaging characteristics assists in confirmation of the
      diagnosis of RON.

PMID- 30113935
TI  - Editor's Spotlight/Take 5: Does THA Improve Social Status Among Turkish Women
      with Developmental Dysplasia of the Hip?

PMID- 30113936
TI  - A Day at the Office: The MACRA-sized Headache-Part 1.

PMID- 30113938
TI  - CORR Insights(r): Patient Perceptions Correlate Weakly With Observed Patient
      Involvement in Decision-making in Orthopaedic Surgery.

PMID- 30113937
TI  - CORR Insights(r): Elevated Expression of Transforming Acidic Coiled-Coil
      Containing Protein 3 (TACC3) Is Associated With a Poor Prognosis in Osteosarcoma.

PMID- 30113939
TI  - American Joint Replacement Registry Risk Calculator Does Not Predict 90-day
      Mortality in Veterans Undergoing Total Joint Replacement.
AB  - BACKGROUND: The American Joint Replacement Registry (AJRR) Total Joint Risk
      Calculator uses demographic and clinical parameters to provide risk estimates for
      90-day mortality and 2-year periprosthetic joint infection (PJI). The tool is
      intended to help surgeons counsel their Medicare-eligible patients about their
      risk of death and PJI after total joint arthroplasty (TJA). However, for a
      predictive risk model to be useful, it must be accurate when applied to new
      patients; this has yet to be established for this calculator. QUESTIONS/PURPOSES:
      To produce accuracy metrics (ie, discrimination, calibration) for the AJRR
      mortality calculator using data from Medicare-eligible patients undergoing TJA in
      the Veterans Health Administration (VHA), the largest integrated healthcare
      system in the United States, where more than 10,000 TJAs are performed annually.
      METHODS: We used the AJRR calculator to predict risk of death within 90 days of
      surgery among 31,214 VHA patients older than 64 years of age who underwent
      primary TJA; data was drawn from the Veterans Affairs Surgical Quality
      Improvement Project (VASQIP) and VA Corporate Data Warehouse (CDW). We then used
      VHA mortality data to evaluate the extent to which the AJRR calculator estimates
      distinguished individuals who died compared with those who did not (C-statistic),
      and graphically depicted the relationship between estimated risk and observed
      mortality (calibration). As a secondary evaluation of the calculator, a sample of
      39,300 patients younger than 65 years old was assigned to the youngest age group
      available to the user (65-69 years) as might be done in real-world practice.
      RESULTS: C-statistics for 90-day mortality for the older samples were 0.62 (95%
      CI, 0.60-0.64) and for the younger samples they were 0.46 (95% CI, 0.43-0.49),
      suggesting poor discrimination. Calibration analysis revealed poor correspondence
      between deciles of predicted risk and observed mortality rates. Poor
      discrimination and calibration mean that patients who died will frequently have a
      lower estimated risk of death than surviving patients. CONCLUSIONS: For Medicare
      eligible patients receiving TJA in the VA, the AJRR risk calculator had a poor
      performance in the prediction of 90-day mortality. There are several possible
      reasons for the model's poor performance. Veterans Health Administration
      patients, 97% of whom were men, represent only a subset of the broader Medicare
      population. However, applying the calculator to a subset of the target population
      should not affect its accuracy. Other reasons for poor performance include a lack
      of an underlying statistical model in the calculator's implementation and simply
      the challenge of predicting rare events. External validation in a more
      representative sample of Medicare patients should be conducted to before assuming
      this tool is accurate for its intended use. LEVEL OF EVIDENCE: Level I,
      diagnostic study.

PMID- 30113940
TI  - An introduction to the Biennial Review of Pain.

PMID- 30113941
TI  - How expectations influence pain.

PMID- 30113942
TI  - Postoperative pain, analgesia, and recovery-bedfellows that cannot be ignored.

PMID- 30113943
TI  - Chronic pain as embodied defence: implications for current and future
      psychological treatments.

PMID- 30113944
TI  - The brain on opioids.

PMID- 30113946
TI  - Global burden of pain and global pain policy-creating a purposeful body of
      evidence.

PMID- 30113947
TI  - Postmodern pain education: "from being to becoming".

PMID- 30113948
TI  - From evidence to influence: dissemination and implementation of scientific
      knowledge for improved pain research and management.

PMID- 30113945
TI  - Using stratified medicine to understand, diagnose, and treat neuropathic pain.

PMID- 30113951
TI  - The exceptional role of the first division of the trigeminal nerve.

PMID- 30113950
TI  - Education in pain and palliative care in the low- and middle-income countries of
      the Asia Pacific region.

PMID- 30113949
TI  - A bright future? Optogenetics in the periphery for pain research and therapy.

PMID- 30113954
TI  - Pain pathogenesis in rheumatoid arthritis-what have we learned from animal
      models?

PMID- 30113955
TI  - On Waiting Rooms.

PMID- 30113952
TI  - Chronic pain and mental health: integrated solutions for global problems.

PMID- 30113956
TI  - The Comfort Theory as a Theoretical Framework Applied to a Clinical Case of
      Hospital at Home.
AB  - The comfort theory was applied in the development of a nursing process for the
      clinical case of an older adult with pneumonia treated under hospital at home. It
      was observed that the theory is easy to apply in the domiciliary context and that
      it allows the implementation of a holistic care plan.

PMID- 30113953
TI  - Exercise-induced pain and analgesia? Underlying mechanisms and clinical
      translation.

PMID- 30113957
TI  - Do-Not-Resuscitate in Iranian Muslim Families: A Conventional Content Analysis.
AB  - Families of patients who are dying have a key role in decisions regarding do-not
      resuscitate orders. The objective of this study was to explore the aspects and
      characteristics of this decision by the families of Muslim patients with cancer.
      This study is a conventional content analysis. Eighteen families who met the
      inclusion criteria participated in this study and were selected by purposive
      sampling. Data collection was done by a semistructured interview (each interview
      was 60-110 minutes). The data analysis was performed using content analysis. The
      data analysis introduced 4 main categories and 8 subcategories: (a) feeling
      duality ("sacrifice against selfishness," and "logic against emotion"), (b)
      religious beliefs ("guilt" and "miracle"), (c) stigmatized ("purgatory talk" and
      "family rejection") and (d) decision-making mediators ("religious clergymen" and
      "the application of the deceased"). Maybe, since the effect of religion in Iran
      is more significant than other elements such as ethnicity and law, it is possible
      to receive help from clergymen. It seems necessary for Iran's Ministry of Health
      and Medical Education to plan clinical guidelines in this context.

PMID- 30113958
TI  - Estimating Life Expectancy From Chinese Medicine Could Improve End-of-Life Care
      in Terminally Ill Cancer Patients.
AB  - Preparing for a good death is an important and meaningful concept in Chinese
      culture because people hope to know residual life to make effort for their
      unfinished business. However, the family of terminally ill patients with cancer
      may be annoyed and frustrated about unexpected bereavement if they have
      unresolved conflicts with the loved one, missing a chance for declaring love,
      untimely apologizing and saying goodbye. The study aimed to explore this
      difficult issue. The medical records of 121 deceased terminally ill patients with
      cancer at National Cheng Kung University Hospital between December 2010 and
      February 2012 were reviewed. The signs and awareness of dying among these
      patients were collected using palliative routine instruments in the hospice ward.
      The top 3 most prevalent dying signs were coolness and cyanosis (prevalence
      98.3%, median period from the first documented dying sign to death 2 days, P =
      .028), mirror-like tongue (prevalence 94.2%, median period 5 days, P = .007), and
      earlobe crease (prevalence 93.4%, median period 4 days, P = .052). In addition,
      the prevalence of dying awareness was 71.1% (median period 4 days, P = .001).
      Furthermore, terminal agitation was identified more frequently in terminally ill
      patients with hepatoma and colon cancer (adjusted odds ratio = 3.240, P = .043),
      but turbid sclera with edema was noted more often in terminally ill patients with
      head and neck cancer (adjusted odds ratio = 5.698, P = .042). The results provide
      evidence to support clinical practice, offering knowledge and techniques to
      health care providers, and increasing quality of life for terminally ill patients
      with cancer.

PMID- 30113960
TI  - Survey to Assess Interest in a Mindfulness Intervention at a Midwifery and
      Women's Health Clinic.
AB  - We conducted a voluntary survey among ethnically and socioeconomically diverse
      women. About half of the respondents reported experiencing at least one health
      issue; over half were interested in attending a mindfulness class to reduce
      stress. Our study suggests interest in participating in a mindfulness
      intervention, primarily among those with more health issues.

PMID- 30113959
TI  - Yoga for Teens With Irritable Bowel Syndrome: Results From a Mixed-Methods Pilot
      Study.
AB  - Irritable bowel syndrome (IBS) is a common condition associated with recurrent
      abdominal pain and altered bowel habits. It is particularly pernicious to youth,
      who may withdraw from life tasks due to pain, diarrhea, and/or fear of symptoms.
      Emotional stress exacerbates IBS symptoms, and mind-body interventions may be
      beneficial. In this mixed-methods study of 18 teens aged 14 to 17 years
      undertaking a 6-week Iyengar yoga intervention, we aimed to identify treatment
      responders and to explore differences between responders and nonresponders on a
      range of quantitative outcomes and qualitative themes related to yoga impact,
      goodness of fit, and barriers to treatment. Half of the teens responded
      successfully to yoga, defined as a clinically meaningful reduction in abdominal
      pain. Responders differed from nonresponders on postintervention quantitative
      outcomes, including reduced abdominal pain, improved sleep, and increased
      visceral sensitivity. Qualitative outcomes revealed that responders reported
      generalized benefits early in treatment and that their parents were supportive
      and committed to the intervention. Responders and nonresponders alike noted the
      importance of home practice to achieve maximal, sustained benefits. This study
      reveals the need for developmentally sensitive yoga programs that increase
      accessibility of yoga for all patients.

PMID- 30113961
TI  - Exploring Cultural Health Practices at a Midwestern University.
AB  - This study investigated complementary health practices (CHPs) at a Midwestern
      state university to examine regional usage rates. Study results demonstrated a
      high use of CHPs as compared with national studies, supporting significance of
      incorporating CHPs in the nursing curriculum to ensure culturally competent and
      safe care for all populations.

PMID- 30113962
TI  - Minding the Mind: Bioactives and Nutrients in Green Leafy Vegetables Slow
      Cognitive Decline.

PMID- 30113963
TI  - HIV Screening, Testing, and Preexposure Prophylaxis: Obligations of Holism.

PMID- 30113964
TI  - Incidence of Combat Sport-Related Mild Traumatic Brain Injuries Presenting to the
      Emergency Department From 2012 to 2016.
AB  - OBJECTIVES: We sought to investigate the incidence and characteristics of
      traumatic brain injuries [mild traumatic brain injury (MTBI)] presenting to the
      emergency department as a result of boxing, wrestling, and martial arts (MA).
      DESIGN: Retrospective cross-sectional study of MTBI in combat sport athletes who
      were evaluated in emergency departments in the United States. SETTING: Patient
      data were taken from the National Electronic Injury Surveillance System.
      PARTICIPANTS: All patients with MTBI from 2012 to 2016, which occurred during
      participation in boxing, MA, or wrestling. INTERVENTIONS: None. MAIN OUTCOME
      MEASURES: The incidence of combat sport-related MTBI presenting to emergency
      departments in the United States. RESULTS: The mean annual incidence of MTBI due
      to wrestling was significantly larger (269.3 per 100 000 person-years) than
      boxing (85.6 per 100 000 person-years) and MA (61.0 per 100 000 person-years) (P
      < 0.01). The average age at injury was significantly lower for wrestling compared
      with boxing and MA (15.0 years [SD +/- 3.9] vs 21.7 years [SD +/- 8.2] vs 19.9
      years [SD +/- 10.5]; P < 0.01). A significantly larger proportion of MTBIs
      (95.3%; P < 0.01) in patients younger than 20 years were related to wrestling,
      compared with boxing (55.8%) and MA (54.1%). Most patients with combat sport
      related MTBIs were treated and discharged (96.3%), with only 1.7% of patients
      being admitted and 0.6% of patients being held for observation. CONCLUSION:
      Combat sports athletes are at high risk of sustaining an MTBI. Such athletes
      presenting to the emergency department for combat sport-related MTBI were more
      likely to be male and younger than 20 years. Of these athletes, wrestlers
      experience the highest incidence of MTBI-related emergency department visits.

PMID- 30113965
TI  - Concussion in Motorsport? Experience, Knowledge, Attitudes, and Priorities of
      Medical Personnel and Drivers.
AB  - OBJECTIVE: To assess concussion experiences, knowledge, and attitudes of
      motorsport medical personnel and drivers and to determine priority areas
      regarding concussion within the sport. DESIGN: Sequential mixed-method design.
      Part 1: stakeholder interviews; part 2: cross-sectional online survey. SETTING:
      United Kingdom. PARTICIPANTS: Part 1: key motorsport stakeholders (N = 8); part
      2: motorsport medical personnel and drivers (N = 209) representing amateur and/or
      professional 4-wheeled motorsport. MAIN OUTCOME MEASURES: Concussion experience,
      knowledge, attitudes, and perceived priority areas. RESULTS: Thirty-one percent
      of surveyed drivers (age = 37.91 +/- 13.49 years: 89% male) reported suffering
      from concussion in motorsport. Eighty-seven percent of surveyed medical personnel
      (age = 48.60 +/- 10.68 years: 74% male) reported experience with concussed
      drivers, and 34% reported feeling pressured to clear a driver with concussion.
      Gaps in knowledge and misperceptions about concussion were reported in both
      groups, and disparity between concussion attitudes emerged between drivers and
      medical personnel. Application of assessment and management procedures varied
      between medical personnel and there was evidence motorsport policy and concussion
      guidelines may not be directly followed. According to both medical personnel
      (77%) and drivers (85%), "education and training" is the top priority area for
      the sport. CONCLUSIONS: There is clear evidence of concussions in motorsport, but
      accurate knowledge about this injury is missing. Concussion education and
      training for all drivers and medical personnel is required. Additional
      investigations into concussion attitudes are advised to complement and advance
      simple educational initiatives. Further investigation is also required to
      determine how to best support motorsport medical personnel, and general
      practitioners, who hold significant responsibility in guiding drivers from
      diagnosis to return to racing, and to support the effective implementation of
      policy.

PMID- 30113966
TI  - Quality-of-Life in Achilles Tendinopathy: An Exploratory Study.
AB  - OBJECTIVE: This research aimed to explore the quality-of-life and experiences of
      people with Achilles tendinopathy. DESIGN: This mixed-methods research used the 8
      dimension Assessment of Quality-of-Life (AQoL-8D), focus groups and grounded
      theory analysis. AQoL-8D scores were compared with population normative scores.
      In focus groups, participants discussed their experiences with Achilles
      tendinopathy. SETTING: An online survey was completed, followed by focus groups
      and interviews held at the University of Canberra. PARTICIPANTS: Adults with
      Achilles tendon pain were eligible to participate in the online survey, which was
      distributed through email and social media. RESULTS: Complete survey responses
      were obtained from 92 individuals, and 11 individuals participated in focus
      groups and interviews. AQoL-8D scores were significantly lower in those with
      Achilles tendinopathy (79 +/- 11 vs 81 +/- 13). AQoL-8Ds of mental health, pain,
      senses, and the physical "super dimension" were also significantly lower. The
      difference exceeded the AQoL-8D minimum clinically important difference of 6%
      only for the pain dimension. Themes identified included adapting lifestyles,
      living with the condition, changes in mental and social well-being, conflict with
      identity, frustration, and individual experiences. CONCLUSIONS: Achilles
      tendinopathy is associated with a lower quality-of-life score, but on average,
      the difference does not exceed the minimum clinically important difference. In
      focus groups, some individuals described profound impacts on their life. This
      discrepancy likely reflects the variability of the impact across individuals. For
      some people, the effect is minimal, yet for those who tie their identity and
      social activities to fitness and physical activity, the effect can be profound.

PMID- 30113968
TI  - Evaluation of Muscle Injuries in Professional Football Players: Does Coach
      Replacement Affect the Injury Rate?
AB  - OBJECTIVES: To assess the incidence and characteristics of muscle injuries in
      professional football players and to assess if coach dismissal may be related
      with muscle injuries within 1-month period from the dismissal. DESIGN:
      Prospective cohort study during 3 consecutive seasons. SETTING: Turkish Super
      League football teams. PARTICIPANTS: One hundred eighteen male football players.
      MAIN OUTCOME MEASURES: Data on time-loss muscle injuries confirmed using magnetic
      resonance imaging were recorded, including type, body part, duration, and lay-off
      time, and training session and match exposure times. The muscle injury rate was
      evaluated at 2 weeks and 30 days after coach dismissal. RESULTS: In total, 124
      muscle injuries were recorded, with injury incidences of 2.3 muscle injuries per
      1000 hours of exposure overall, 1.2 in training sessions, and 13.6 in matches.
      Injury time loss ranged from 3 to 67 days (median, 13 days). Eighteen percent of
      the injuries (n = 23) were recurrent; no association was found between recurrence
      rate and the player's age or position (P = 0.15, P = 0.27, respectively).
      Recurrent injuries caused more severe injuries (26.1%, P = 0.02) and longer
      median lay-off time (P = 0.01). During the study, teams A and B replaced 7 and 3
      coaches, respectively. The injury incidence increased to 5.3 per 1000 hours of
      exposure in the 2 weeks after the coach dismissal, and decreased to 4.5 within 1
      month of coach dismissal. CONCLUSION: Given the link between coach dismissal and
      increased rates of muscle strain injuries, increased attentiveness to preventing
      muscle injuries during coaching transitions and to the impact of new training
      regimens is required by trainers and medical teams.

PMID- 30113967
TI  - Concussion in Adolescents Impairs Heart Rate Response to Brief Handgrip Exercise.
AB  - OBJECTIVE: Test the hypotheses that (1) concussion in adolescents impairs
      autonomic neural control of heart rate (HR), and (2) HR reactivity improves with
      symptom resolution. DESIGN: Observational, case-control. PARTICIPANTS: Nineteen
      concussed adolescents (8 female adolescents; age 15 +/- 2 years) and 16 healthy
      controls (6 female adolescents, age 15 +/- 2 years). INTERVENTION: All
      participants performed an isometric handgrip (IHG) at 30% maximum voluntary
      contraction lasting 30 seconds. Heart rate (electrocardiogram) and hemodynamic
      responses (photoplethysmographic Finometer) were recorded from 30 seconds of
      baseline and the last 10 seconds of handgrip. MAIN OUTCOME MEASURES: The HR
      response (DeltaHR) at the onset of moderate-intensity IHG using a mixed 1-way
      analysis of variance. RESULTS: A group * time interaction (P < 0.005) indicated
      that handgrip evoked a greater DeltaHR among control participants (13 +/- 10
      beats/min) compared with concussed (6.4 +/- 6.3 beats/min; group P = 0.63; time P
      < 0.001; d = 0.77). CONCLUSION: These preliminary results suggest that a
      concussion impairs the ability to elevate HR at the exercise onset and, given the
      nature of the task, this could be interpreted to reflect reduced ability to
      withdraw cardiovagal control. Therefore, the data support the hypothesis of
      neural cardiac dysregulation in adolescents diagnosed with concussion. CLINICAL
      RELEVANCE: The IHG test could aid concussion diagnosis and support return-to-play
      decisions.

PMID- 30113969
TI  - Normative Data for the Sway Balance System.
AB  - OBJECTIVE: Static balance, postural stability, and reaction time are commonly
      impaired after a sport-related concussion. The Sway Balance System assesses
      postural sway (ie, stability) and simple reaction time using the triaxial
      accelerometer built into iOS mobile devices. The purpose of this study was to
      provide normative data for children and adolescents and to examine for age and
      sex differences on the Sway Balance System. DESIGN: Cross-sectional study.
      SETTING: Middle and high schools across the United States. PARTICIPANTS:
      Participants were 3763 youth aged 9 to 21 years who completed the Sway Balance
      System Sports protocol in accordance with the company's recommended methods (ie,
      1 acclimation trial and 2-3 baseline tests). INDEPENDENT VARIABLES: Age and sex.
      MAIN OUTCOME MEASURES: Sway Balance score (0-100) and Sway Reaction Time score (0
      100). STATISTICAL ANALYSIS: A multivariate analysis of variance examined the
      effects of age and sex on balance and reaction time scores. RESULTS: Sway Balance
      and Reaction Time scores significantly differed by age [F(10, 7494) = 39.68, P <
      0.001, V = 0.10, etap = 0.05] and sex [F(4, 7494) = 55.29, P < 0.001, V = 0.06,
      etap = 0.03]. Post hoc analyses revealed that older groups generally had better
      scores than younger groups on all balance comparisons (ps < 0.001) and many
      reaction time comparisons. Girls performed better than boys on balance [F(2,
      3747) = 53.79, P < 0.001, etap = 0.03] and boys had faster reaction times [F(2,
      3747) = 37.11, P < 0.001, etap = 0.02]. CONCLUSIONS: Age and sex are important
      factors to consider when assessing Balance and Reaction Time scores using the
      Sway Balance System's Sports protocol in youth. We provide age- and sex-based
      normative values for the Sway Balance System, which will likely be helpful when
      using this technology to assess and manage concussions.

PMID- 30113970
TI  - Take It or Leave It: A Meta-analysis of Perioperative ACE Inhibitors and ARBs.

PMID- 30113971
TI  - Critically Ill, Then Chronically Painful: Pain and Interference With Everyday
      Life.

PMID- 30113972
TI  - Another Win for Lidocaine, Another Loss for Magnesium?

PMID- 30113973
TI  - Dyeing to Find Out How an "AWEsim" Bundle Can Impact Anesthesia Work Environment
      Contamination.

PMID- 30113974
TI  - Intraoperative Transfusion Guidelines: Promoting Clinician Adherence in the
      Operating Room.

PMID- 30113975
TI  - Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers
      Before Elective Noncardiac Surgery: An Ongoing Dilemma.

PMID- 30113976
TI  - Local Anesthetics as...Cancer Therapy?

PMID- 30113977
TI  - Fibrinogen Concentrate: Is It Standard Currency or Bitcoin in Bleeding
      Management?

PMID- 30113978
TI  - American Society for Enhanced Recovery and Perioperative Quality Initiative Joint
      Consensus Statement on Postoperative Gastrointestinal Dysfunction Within an
      Enhanced Recovery Pathway for Elective Colorectal Surgery: Erratum.

PMID- 30113979
TI  - Quantifying Lymph Nodes During Lymph Node Transplantation: The Role of
      Intraoperative Ultrasound.
AB  - Quantifying lymph nodes in vascularized lymph node transfer (VLNT) has been
      performed using preoperative percutaneous ultrasound. The higher resolution and
      accuracy of intraoperative ultrasound (IOUS) over transcutaneous ultrasound has
      been demonstrated in the radiology literature for the identification and
      characterization of finer structures including hepatic lesions, pancreatic
      lesions, and biliary or pancreatic ducts. We hypothesize that IOUS during VLNT
      would be a superior method to quantify and map lymph nodes in our flaps. A
      prospectively collected database of patients undergoing VLNT over 3 years
      (October 2014 to October 2017) was reviewed. Patients who underwent IOUS during
      flap harvest, before pedicle ligation to simultaneously map and quantify the
      number of lymph nodes were included in the study. Twenty-one patients with an
      average age of 58.7 years and a mean BMI of 32.3 underwent VLNT with IOUS for
      chronic lymphedema during the study period. Extremity lymphedema was classified
      as Campisi IB (n = 7), IIA (n = 7), IIB (n = 5), and IIIA (n = 2). There were 14
      superficial circumflex iliac artery flaps, including 4 performed concomitantly
      with a deep inferior epigastric perforator flap, 1 transverse cervical artery
      flap, and 6 omental flaps. The average number of lymph nodes transferred per IOUS
      was 4.3 for superficial circumflex iliac artery flaps, 4 for the transverse
      cervical artery flap, and 5.2 for the omental flaps. Intraoperative ultrasound
      allows the lymphatic surgeon to precisely map the location of lymph nodes which
      can guide intraoperative decision making. As there is no data correlating the
      number of lymph nodes transferred and outcomes after VLNT, developing a precise
      intraoperative quantification method is important.

PMID- 30113980
TI  - Rectus Abdominis Myofascial Flap for Vaginal Reconstruction After Pelvic
      Exenteration.
AB  - BACKGROUND: Several techniques for vaginal reconstruction after pelvic
      exenteration such as myocutaneous and myoperitoneal flaps are available. However,
      the use of a myofascial flap has not been previously described. Thus, the
      objective of this article is to present our experience of vaginal reconstruction
      with rectus abdominis myofascial (RAMF) flap. METHODS: Between May 2008 and March
      2017, 16 patients underwent anterior, posterior, or total pelvic exenteration
      with RAMF flap vaginal reconstruction. Patient records were systematically
      reviewed; demographic, clinic and pathologic, operative details, flap-related and
      non-flap-related complications, and risk factors for wound healing are reported.
      Quality of life and sexual function were also investigated. RESULTS: Eleven
      (68.8%) of 16 patients died during the follow-up (29.1 +/- 25 months), whereas 5
      (31.3%) are still alive. Early complications were reported in 7 patients (43.8%),
      with 2 (12.5%) flap-related and 5 (31.3%) non-flap-related complications.
      Similarly, late complications were reported in 5 patients (31.3%), with 2 (12.5%)
      flap-related and 3 (18.8%) non-flap-related complications. Quality of life
      measured by SF-36 (Survey Short Form 36) significantly improved at 12-month
      follow-up in comparison with baseline (physical component summary 31.5 +/- 4.8 vs
      26.8 +/- 2.9; P = 0.027; mental component summary 29.5 +/- 6.0 vs 25.9 +/- 2.0; P
      = 0.042). CONCLUSIONS: This study demonstrates for the first time that RAMF flap
      vaginal reconstruction after pelvic exenteration is an efficacious and safe
      technique. Furthermore, it is associated with a significant improvement of
      quality of life and sexual function in those women who had sexual intercourse
      before surgery.

PMID- 30113982
TI  - Efficacy of Autologous Platelet Concentrates as Adjuvant Therapy to Surgical
      Excision in the Treatment of Keloid Scars Refractory to Conventional Treatments:
      A Pilot Prospective Study.

PMID- 30113981
TI  - Lower Eyelid Reconstruction Using a Nasolabial, Perforator-based V-Y Advancement
      Flap: Expanding the Utility of Facial Perforator Flaps.
AB  - BACKGROUND: Reconstruction of the lower eyelid represents a unique challenge to
      the reconstructive surgeon. Studies evaluating the utility of the nasolabial V-Y
      advancement flap in lower eyelid reconstruction are limited and techniques to
      optimize outcomes following eyelid reconstruction with this technique are not
      well described. We seek to evaluate our experience and outcomes with lower eyelid
      reconstruction using the nasolabial perforator-based V-Y advancement flap.
      METHODS: After institutional review board approval, medical charts of all
      patients who underwent lower eyelid reconstruction using the nasolabial
      perforator-based V-Y advancement flap between February 2013 and October 2017 were
      reviewed. Data regarding etiology, location of the lesion, lower eyelid defect,
      methods of reconstruction, postoperative complications, and follow up duration
      were collected and analyzed. RESULTS: Over the study period, 5 patients (3 male)
      underwent lower eyelid reconstruction after oncologic resection of melanoma (n =
      1) and nonmelanoma (n = 4) skin cancer using the nasolabial perforator-based V-Y
      advancement flap at a mean age of 69 years (range, 56-82 years). Median follow-up
      duration was 5.9 months (interquartile range, 2.25-25.9). A mean of 5.4 (range, 2
      10) perforators were included in the initial flap design. After completion of
      flap dissection and perforator division, a mean of 4.4 (range, 2-7) perforators
      were preserved and included in the flap. All flaps demonstrated clinical
      viability with no cases of partial or total flap loss. One patient developed an
      asymptomatic ectropion during the follow-up period. CONCLUSIONS: The nasolabial,
      perforator-based V-Y advancement flap is a reliable reconstructive method for
      lower eyelid defects.

PMID- 30113983
TI  - Letter to the Editor Following "A Combination Flap for Nasal Defect
      Reconstruction" by Rajshree Jayarajan, Annals of Plastic Surgery, 2018.

PMID- 30113985
TI  - Sensory phenotype and risk factors for painful diabetic neuropathy: a cross
      sectional observational study: Erratum.

PMID- 30113984
TI  - Topical Deferoxamine Alleviates Skin Injury and Normalizes Atomic Force
      Microscopy Patterns Following Radiation in a Murine Breast Reconstruction Model.
AB  - BACKGROUND: Breast cancer is most commonly managed with a combination of tumor
      ablation, radiation, and/or chemotherapy. Despite the oncologic benefit of these
      treatments, the detrimental effect of radiation on surrounding tissue challenges
      the attainment of ideal breast reconstruction outcomes. The purpose of this study
      was to determine the ability of topical deferoxamine (DFO) to reduce cutaneous
      ulceration and collagen disorganization following radiotherapy in a murine model
      of expander-based breast reconstruction. METHODS: Female Sprague-Dawley rats (n =
      15) were divided into 3 groups: control (expander), XRT (expander + radiation),
      and DFO (expander + radiation + deferoxamine [DFO]). Expanders were placed in a
      submusculocutaneous plane in the right upper back and ultimately filled to 15 mL.
      Radiation was administered via a fractionated dose of 28 Gy. Deferoxamine was
      delivered topically for 10 days following radiation. After a 20-day recovery
      period, skin ulceration and dermal type I collagen organization were analyzed.
      RESULTS: Compared with control, the XRT group demonstrated a significant increase
      in skin ulceration (3.7% vs 43.3%, P = 0.00) and collagen fibril disorganization
      (26.3% vs 81.8%, P = 0.00). Compared with the XRT group, treatment with topical
      DFO resulted in a significant reduction in ulceration (43.3% vs 7.0%, P = 0.00)
      and fibril disorganization (81.8% vs 15.3%, P = 0.00). There were no statistical
      differences between the control and DFO groups in skin ulceration or collagen
      disorganization. CONCLUSIONS: This study suggests topical DFO is capable of
      reducing skin ulceration and type I collagen fibril disorganization following
      radiotherapy. This novel application of DFO has potential to enhance expander
      based breast reconstruction outcomes and improve quality of life for women
      suffering the devastating effects of breast cancer.

PMID- 30113986
TI  - Hyperpolarization-activated cyclic nucleotide-gated channels contribute to
      spontaneous activity in L4 C-fiber nociceptors, but not Abeta-non-nociceptors,
      after axotomy of L5-spinal nerve in the rat in vivo: Erratum.

PMID- 30113987
TI  - Case Report of a Syncope Episode in a Healthy Male Adult Participant During
      Single-Pulse Transcranial Magnetic Stimulation.

PMID- 30113989
TI  - Helping to Prevent Malignant Transformation in Bipolar Disorder: A Response to
      Post.

PMID- 30113990
TI  - Treatment of Possible PERM Underlying Malignant Catatonia and Accompanying
      Psychotic Symptoms With Modified Electroconvulsive Therapy: A Case Report.

PMID- 30113988
TI  - Effectiveness of Electroconvulsive Therapy in Patients With Major Depressive
      Disorder and Comorbid Borderline Personality Disorder.
AB  - OBJECTIVE: Previous research suggests that electroconvulsive therapy (ECT)-the
      criterion standard for the treatment of severe depression-is not as effective
      when the patient has comorbid borderline personality disorder (BPD). The ECT
      outcomes of patients with and without BPD were compared in a retrospective chart
      review to test this claim. METHODS: We enrolled 137 patients with a diagnosis of
      major depressive disorder who completed the McLean Screening Instrument for
      Borderline Personality Disorder. Twenty-nine patients had positive screening
      scores for BPD. The difference in Patient Health Questionnaire (PHQ-9) scores
      before and after ECT was compared between patients with and without BPD. Follow
      up PHQ-9 scores determined after treatment were collected and analyzed. RESULTS:
      Electroconvulsive therapy equally improved symptoms of depression as measured by
      PHQ-9 score in both patients who screened positive and patients who screened
      negative for BPD. No difference in the increase in PHQ-9 scores between these 2
      groups was noted 1 month after treatment (P = 0.19). CONCLUSIONS: These data
      showed that a positive BPD screen does not necessarily predict a poorer response
      to ECT, nor does it predict greater symptom recurrence after ECT. This does not
      suggest that ECT is necessarily an appropriate treatment for major depressive
      disorder in patients with a comorbid BPD, given the limitations of screening
      instruments.

PMID- 30113991
TI  - ECT as a Novel Treatment for PTSD.

PMID- 30113992
TI  - Comparison of Site Localization Techniques for Brain Stimulation.
AB  - OBJECTIVES: The dorsolateral prefrontal cortex (DLPFC) is a commonly targeted
      site using noninvasive brain stimulation techniques. Methods used to localize
      this site commonly rely on the International 10-20 electroencephalography (EEG)
      system, including elastic EEG caps, which stretch to accommodate varying head
      sizes, as well as the Beam F3 algorithm, which uses scalp measurements to
      calculate the location of the DLPFC. Both methods have been validated against
      magnetic resonance imaging-based DLPFC localization and are regularly used in
      research centers and clinics, but an in vivo comparison of reliability has not
      yet been conducted. This study examines whether Beam F3 and EEG cap methods
      differ in DLPFC localization, when applied by different practitioners (measurers)
      on a range of subjects. Further, whether measurer experience or subject head
      characteristics influence localization. METHODS: Measurers (n = 5) of varying
      levels of experience identified the location of the left DLFPC on subjects (n =
      6) with varying head sizes, using both Beam F3 and EEG cap methods. An
      independent assessor recorded the measurers' placements along the anterior
      posterior and medial-lateral planes. Values were normalized to the subjects' mean
      nasion-inion and tragus-tragus distances and examined using a mixed effects
      repeated measures analysis. RESULTS: The Beam F3 method resulted in significantly
      more anterior placements (~11.5 mm) compared with the EEG cap. Subjects with
      smaller head sizes had more anterior placements, compared with medium and large
      heads, regardless of the method used. There was no significant difference between
      methods along the medial-lateral plane. Measurer experience did not significantly
      influence DLPFC localization. CONCLUSIONS: Beam F3 and EEG cap methods resulted
      in similar DLPFC placements, with a small difference along the anterior-posterior
      plane. Measurer experience did not affect either method, suggesting that 2 weeks
      of training is sufficient to achieve competency. Training and reliability of
      DLPFC placement therefore do not represent substantial barriers to application of
      either method. Special care should be taken with subjects with small heads as
      both methods resulted in more anterior DLPFC placements.

PMID- 30113993
TI  - Protocol Duodenal Graft Biopsies Aid Pancreas Graft Surveillance.
AB  - BACKGROUND: Histological evaluation of the pancreas graft is usually done on
      demand resulting in significant delays. This analysis reports on endoscopic
      protocol duodenal graft biopsies at regular intervals to determine feasibility,
      safety and monitoring benefits. METHODS: Protocol duodenal graft biopsies in 27
      18 consecutive pancreas transplants (10 simultaneous pancreas kidney [SPK], 17
      pancreas after kidney [PAK]) with a follow-up of a minimum of 12 months were
      performed at days 14, 30, 90, 180, 360, 430. UPMC classification for intestinal
      rejection was used. C4d staining was performed when antibody mediated rejection
      was suspected. RESULTS: Overall patient and pancreas graft survival was 100% and
      93% at a mean follow-up of 2.8 years. 167 endoscopic biopsy procedures were
      performed in 27 grafts without any complication. Biopsies revealed rejection in 3
      (30%) SPK recipients and in 15 (82%) of PAK recipients as early as 14 days
      posttransplant. Two patients underwent PAK retransplantation diagnosed with acute
      rejection at day 180. All except 1 recipient being treated for rejection, showed
      histological improvement following antirejection treatment. Following transient
      treatment success, a total of 3 pancreas grafts were lost for immunological
      reason. One loss was immediate despite antirejection treatment, 1 secondary to
      nonresolving rejection at 7 months and the third due to recurrent rejection 15
      months posttransplantation. Additionally, biopsies detected vascular (venous
      thrombosis) and overimmunosuppression (CMV infection) complications. CONCLUSIONS:
      Protocol graft duodenal biopsies detect complications following whole organ
      pancreas transplantation, are useful in guiding therapy and carry potential for
      improving outcome.

PMID- 30113994
TI  - Clinical Relevance of a Balance Training Program on Liver Transplant Patients. A
      Randomized Controlled Trial.
AB  - BACKGROUND: Although some studies have reported significant improvements in
      physical function and strength after training programs on Liver Transplant (LT)
      recipients, there is a lack of knowledge on how it affects in static and dynamic
      balance, being an important part of these participants' tasks development. The
      aim of the study was to determine the effects of a 6-month multicomponent circuit
      training program on static and dynamic balance in LT participants. METHODS: 54
      participants were randomized at 6 months after LT into 2 groups: exercise group
      (EXER) and control group (CONTROL), with repeat testing at 6 (baseline) and 12
      months after LT. The intervention consisted in a multicomponent training,
      including balance, strength, endurance and flexibility training, with exercises
      arranged in a circuit setup and a moderate intensity with high perceived
      exertion. Training sessions were performed in the hospital facilities with
      qualified trainers. To determine differences overtime between EXER and CONTROL,
      mixed regression linear models with subject variable as random factor and
      variables of treatment duration, type and interaction as predictors were used.
      RESULTS: EXER showed significant differences (p<.05) compared to CONTROL in all
      variables of static and dynamic balance, hip strength (+49% vs +13%), agility (
      16% vs -1%) and flexibility (+78% vs -26%). Adherence to the intervention was
      94%, and 80% of the participants continued voluntarily training after the 6
      months. CONCLUSIONS: This study demonstrated that a multicomponent circuit
      training program at a moderate intensity with high perceived exertion could
      reduce the probability of injuries because improves balance on LT recipients.

PMID- 30113995
TI  - Blocking CD40/CD40L for Chimerism-Based Tolerance: Lost in Translation?

PMID- 30113996
TI  - Addition of Anti-CD40 Monoclonal Antibody to Nonmyeloablative Conditioning With
      Belatacept Abrogated Allograft Tolerance Despite Induction of Mixed Chimerism.
AB  - BACKGROUND: We recently reported anti-CD40 monoclonal antibody and rapamycin
      (aCD40/rapa) to be a reliable, nontoxic, immunosuppressive regimen for combined
      islet and kidney transplantation (CIKTx) in nonhuman primates (NHPs). In the
      current study, we attempted to induce allograft tolerance through the mixed
      chimerism approach using a conditioning regimen with aCD40 and belatacept (Bela).
      METHODS: Five CIKTx or kidney transplant (KTx) recipients were treated with
      aCD40/rapa for 4 months. All recipients then received a conditioning regimen
      including horse anti-thymocyte globulin (hATG) and aCD40/Bela. The results were
      compared with previous reports of recipients treated with Bela-based regimens.
      RESULTS: All 3 CIKTx recipients developed mixed chimerism, which was
      significantly superior to that observed in the previous Bela-based studies.
      Nevertheless, all CIKTx recipients in this study lost their islet and renal
      allografts as a result of cellular and humoral rejection on days 140, 89, and 84.
      The 2 KTx-alone recipients were treated with the same conditioning regimen and
      suffered rejection on days 127 and 116, despite the development of excellent
      chimerism. B lymphocyte reconstitution dominated by memory phenotypes was
      associated with early development of donor-specific antibodies in 4/5 recipients.
      In vitro assays showed no donor-specific regulatory T cell (Treg) expansion,
      which has been consistently observed in tolerant recipients with our mixed
      chimerism approach.CONCLUSIONDespite displaying excellent immunosuppressive
      efficacy, costimulatory blockade with anti-CD40 mAb (2C10R4) may inhibit the
      induction of renal or islet allograft tolerance via a mixed chimerism approach.

PMID- 30113997
TI  - Safety of Islet Autotransplantation Following Pancreatectomy for Adenocarcinoma.
AB  - BACKGROUND: total pancreatectomy with intraportal islet autotransplantation
      (TPIAT) rather than partial pancreatectomy could represent a major shift in the
      management of patients with resectable pancreatic ductal adenocarcinoma (PDAC)
      when risks of postoperative pancreatic fistula are well identified. This approach
      provides a theoretical risk of tumor cell dissemination when islet cells are
      transplanted into the portal vein. Our objective was to demonstrate the safety of
      TPIAT in PDAC in a mouse preclinical model of subcutaneous xenotransplantation of
      human cells isolated from pancreatic specimen during partial pancreatectomy
      performed for PDAC. METHODS: patients requiring pancreatectomy for PDAC were
      prospectively included. Immunocompromized mice were transplanted with pancreatic
      cells isolated from the nonmalignant part of the surgical specimen (experimental
      group). Results were compared to pancreatic tumor implants (control group).
      Pancreatic grafts were explanted at 6 weeks for histological analyses. RESULTS: 9
      patients were included and 31 mice were transplanted. In the experimental group,
      explants were microscopically devoid of tumor cell and no metastasis was
      observed. In the control group, all explants were composed of tumor. CONCLUSIONS:
      we report in a preclinical model the absence of local and distant spreading of
      malignant cells following pancreatic islets xenograft isolated from PDAC
      patients. These data supports the oncological safety of TPIAT as valuable
      alternative to partial pancreatectomy for PDAC patients with a high risk of
      postoperative pancreatic fistula.

PMID- 30113998
TI  - Intraabdominal Complications Following Pediatric Kidney Transplantation:
      Incidence and Risk Factors.
AB  - BACKGROUND: The incidence and types of intraabdominal complications following
      pediatric transplantation are not well established and specific risk groups have
      not been clearly identified. METHODS: A retrospective chart review of all
      pediatric transplant recipients, between 1995 and 2016 was undertaken.
      Intraabdominal complications were grouped into 4 categories: fluid collections,
      gastrointestinal, vascular and urogenital. Donor, recipient, and transplant
      characteristics were evaluated using univariate and multivariate logistic
      regression. RESULTS: There were 146 transplants meeting the inclusion criteria.
      The mean follow up time was 4.6 +/- 3.7 years (range, 0.3-18). The mean weight at
      transplantation was 31.5 +/-16.5kg (range, 9-78), with 24(16%) recipients being <
      15kg and 23% under 5 years of age. Thirty-four (23%) patients had had previous
      abdominal surgery. There were 32 complications identified in 27 (18%) transplant
      recipients.Fluid collections, requiring surgical drainage, developed in 9 (6.2%),
      gastrointestinal surgical complications in 12 (8.2%), vascular complications in 5
      (3.5%) and urogenital complications in 6 (4.1%). There were only 3 graft losses
      due to abdominal complications, all following renal vein thrombosis.Weight <15kg
      at the time of transplant (p=0.016), previous abdominal surgery (p=0.047) and
      intraperitoneal surgical technique (p=0.008) were risk factors in the univariate
      analysis using COX regression models, whereas only weight <15kg (p=0.003) and
      previous abdominal surgery (p=0.008) were retained in the multivariate analysis.
      CONCLUSIONS: Intraabdominal complications occur in almost 1 in 5 pediatric renal
      transplant recipients. Weight <15kg and previous abdominal surgery are risk
      factors for developing such complications.

PMID- 30113999
TI  - A Predictive Risk Scoring System for Clinically Relevant Pancreatic Fistula After
      Pancreaticoduodenectomy.
AB  - BACKGROUND Postoperative pancreatic fistula remains a challenge after
      pancreaticoduodenectomy (PD). This study aimed to establish a scoring system to
      predict clinically relevant postoperative pancreatic fistula (CR-POPF) after PD.
      MATERIAL AND METHODS The clinical records of 361 consecutive patients who
      underwent PD between 2009 and 2017 were reviewed retrospectively. Patients were
      divided into a study group (225 patients) and a validation group (136 patients).
      CR-POPF was defined and classified based on the 2016 ISGPS definition and
      classification system. Univariate and multivariate logistic regression analyses
      were performed and we thus developed a scoring system based on the regression
      coefficient of the multivariate logistic regression model. The predictive value
      was determined using the receiver operating characteristic (ROC) curve. RESULTS A
      predictive scoring system with a maximum of 6 points for CR-POPF was established
      using the following 4 factors: 1 point for soft pancreatic texture (OR 2.09,
      95%CI 1.10-3.98, P=0.025), 1.5 points for main pancreatic duct diameter <=2.5 mm
      (OR 2.72, 95%CI 1.23-5.99, P=0.013), 0.5 points for extended lymphadenectomy (OR
      1.57, 95%CI 1.13-2.18, P=0.007), 0.5 points for a 25-30 g/L postoperative day 1
      serum albumin (OR 1.43, 95%CI 1.02-2.00, P=0.037), and 3 points for postoperative
      day 1 serum albumin <=25 g/L (OR 5.12, 95%CI 1.82-14.41, P=0.002). The ROC curve
      showed that this scoring system was highly predictive for CR-POPF in the
      validation group (AUC=0.806, 95%CI: 0.735-0.878). CONCLUSIONS This 6-point risk
      scoring system will be useful for perioperative risk management of CR-POPF.

PMID- 30114002
TI  - Erratum: Vol. 67, No. 30.

PMID- 30114000
TI  - Emergence of Localized Serogroup W Meningococcal Disease in the United States -
      Georgia, 2006-2016.
AB  - Several countries in Europe and Australia are reporting an increasing incidence
      of Neisseria meningitidis serogroup W (NmW) as a consequence of the rapid
      expansion of a single NmW clone belonging to clonal complex 11 (1-5). Because
      this clone is reported to be associated with more severe disease, unusual
      clinical presentations, and a high case fatality ratio (CFR), it is considered a
      hypervirulent strain (1,6). In the United States, NmW accounts for approximately
      5% of meningococcal disease reported each year, and this proportion has remained
      stable for several years (7). However, localized increases in NmW have been
      reported, most notably in Florida during 2008-2009 (8). In Georgia, NmW accounted
      for only 3% of meningococcal disease cases reported during 2006-2013; however,
      between January 2014 and December 2016, 42% of all reported cases were NmW.
      Surveillance data from Georgia were analyzed to describe the epidemiology and
      clinical characteristics of NmW cases, and whole-genome sequencing of NmW
      isolates was performed for comparison with NmW strains circulating in the United
      States and worldwide. These data indicate that the U.S. NmW strains might have
      evolved from the same ancestor as the hypervirulent strain that is circulating
      globally. Genetic analysis demonstrates that these strains are closely related,
      which would suggest that genetic variation led to the rise of different strains
      from the same ancestor. Given the recent global expansion of this potentially
      hypervirulent NmW lineage, clinicians and public health officials need to remain
      vigilant in obtaining isolates to monitor changes in circulating strains.

PMID- 30114004
TI  - QuickStats: Percentage Distribution* of Adult Day Services Centers,? by Type of
      ServiceS - National Study of Long-Term Care Providers, 2016 .

PMID- 30114003
TI  - Corneal Infections Associated with Sleeping in Contact Lenses - Six Cases, United
      States, 2016-2018.
AB  - Contact lenses, when worn and cared for properly, are a safe and effective form
      of vision correction used by an estimated 45 million Americans. However, contact
      lens wearers are at risk for contact lens-related eye infections, especially when
      wearers do not practice proper contact lens wear and care habits. These
      infections, affecting the cornea and known as microbial keratitis (Figure), can
      lead to serious adverse health outcomes. Because contact lenses are regulated by
      the Food and Drug Administration (FDA) as medical devices, contact lens-related
      corneal infections should be reported to FDA as an adverse event. To illustrate
      their serious health implications, six cases of contact lens-related corneal
      infection, in which sleeping in lenses was reported as the main risk factor, are
      presented. Consequences of infection reported among the identified cases included
      the need for frequent administration of antibiotic eye drops, multiple follow-up
      medical appointments, and permanent eye damage. Health education measures
      directed toward contact lens wearers should emphasize raising awareness of the
      risks of sleeping in contact lenses as well as adherence to all recommendations
      for the wear and care of contact lenses. Additional measures are needed to
      educate eye care professionals about the need to report contact lens-related
      corneal infections to MedWatch, the FDA Safety Information and Adverse Event
      Reporting program (https://www.fda.gov/MedWatch/).

PMID- 30114001
TI  - Contraceptive Use Among Women at Risk for Unintended Pregnancy in the Context of
      Public Health Emergencies - United States, 2016.
AB  - Ensuring access to and promoting use of effective contraception have been
      identified as important strategies for preventing unintended pregnancy (1). The
      importance of ensuring resources to prevent unintended pregnancy in the context
      of public health emergencies was highlighted during the 2016 Zika virus outbreak
      when Zika virus infection during pregnancy was identified as a cause of serious
      birth defects (2). Accordingly, CDC outlined strategies for state, local, and
      territorial jurisdictions to consider implementing to ensure access to
      contraception (3). To update previously published contraceptive use estimates*
      among women at risk for unintended pregnancy? and to estimate the number of women
      with ongoing or potential need for contraceptive services,S,  data on
      contraceptive use were collected during September-December 2016 through the
      Behavioral Risk Factor Surveillance System (BRFSS). Results from 21 jurisdictions
      indicated that most women aged 18-49 years were at risk for unintended pregnancy
      (range across jurisdictions = 57.4%-76.8%). Estimates of the number of women with
      ongoing or potential need for contraceptive services ranged from 368 to 617 per
      1,000 women aged 18-49 years. The percentage of women at risk for unintended
      pregnancy using a most or moderately effective contraceptive method** ranged from
      26.1% to 65.7%. Jurisdictions can use this information to estimate the number of
      women who might seek contraceptive services and to plan and evaluate efforts to
      increase contraceptive use. This information is particularly important in the
      context of public health emergencies, such as the recent Zika virus outbreak,
      which have been associated with increased risk for adverse maternal-infant
      outcomes (2,4-6) and have highlighted the importance of providing women and their
      partners with resources to prevent unintended pregnancy.

PMID- 30114005
TI  - Prevalence of Disabilities and Health Care Access by Disability Status and Type
      Among Adults - United States, 2016.
AB  - Persons with disabilities face greater barriers to health care than do those
      without disabilities (1). To identify characteristics of noninstitutionalized
      adults with six specific disability types (hearing, vision, cognition, mobility,
      self-care, and independent living),* and to assess disability-specific
      disparities in health care access, CDC analyzed 2016 Behavioral Risk Factor
      Surveillance System (BRFSS) data. The prevalences of disability overall and by
      disability type, and access to health care by disability type, were estimated.
      Analyses were stratified by three age groups: 18-44 years (young adults), 45-64
      years (middle-aged adults), and >=65 years (older adults). Among young adults,
      cognitive disability (10.6%) was the most prevalent type. Mobility disability was
      most prevalent among middle-aged (18.1%) and older adults (26.9%). Generally,
      disability prevalences were higher among women, American Indians/Alaska Natives
      (AI/AN), adults with income below the federal poverty level (FPL), and persons in
      the South U.S. Census region. Disability-specific disparities in health care
      access were prevalent, particularly among young and middle-aged adults. These
      data might inform public health programs of the sociodemographic characteristics
      and disparities in health care access associated with age and specific disability
      types and guide efforts to improve access to care for persons with disabilities.

PMID- 30114006
TI  - Prevalence of Five Health-Related Behaviors for Chronic Disease Prevention Among
      Sexual and Gender Minority Adults - 25 U.S. States and Guam, 2016.
AB  - In recent decades, public health awareness of health disparities among lesbian,
      gay, bisexual, and transgender (LGBT) populations has increased (1). Healthy
      People 2020 included objectives to improve health of LGBT persons.? Five key
      health-related behaviors were found to be likely associated with reduced all
      cause mortality: never smoking, performing regular physical activity, consuming
      no or moderate amounts of alcohol, having a normal body weight, and obtaining
      sufficient sleep daily (2). CDC estimated these five health-related behaviors
      among adults aged >=21 years by sexual orientation and transgender status using
      data from the 2016 Behavioral Risk Factor Surveillance System (BRFSS) in 25 U.S.
      states and Guam. Patterns of these five health-related behaviors varied by sexual
      orientation among men and women, and among transgender adults. Lesbian and
      bisexual women were less likely to engage in all five health-related behaviors
      than were heterosexual women (5.4% and 6.9%, respectively, versus 10.6%).
      Compared with cisgenderS adults, male-to-female transgender adults were less
      likely to engage in any two of five health-related behaviors (12.3% versus
      18.6%). Male-to-female transgender adults, however, were more likely to engage in
      any three of five health-related behaviors than were female-to-male transgender
      adults (47.2% versus 28.2%). The number of health-related behaviors did not
      differ between gay or bisexual men and heterosexual men. Continued efforts are
      needed to target LGBT populations for overall well-being, including strategies
      for health promotion and engagement in health-related behaviors.

PMID- 30114008
TI  - Using CDOM optical properties for estimating DOC concentrations and pCO2 in the
      Lower Amazon River.
AB  - Coloured dissolved organic matter (CDOM) is one of the major contributors to the
      absorption budget of most freshwaters and can be used as a proxy to assess non
      optical carbon fractions such as dissolved organic carbon (DOC) and the partial
      pressure of carbon dioxide (pCO2). Nevertheless, riverine studies that explore
      the former relationships are still relatively scarce, especially within tropical
      regions. Here we document the spatial-seasonal variability of CDOM, DOC and pCO2,
      and assess the potential of CDOM absorption coefficient (aCDOM(412)) for
      estimating DOC concentration and pCO2 along the Lower Amazon River. Our results
      revealed differences in the dissolved organic matter (DOM) quality between
      clearwater (CW) tributaries and the Amazon River mainstream. A linear
      relationship between DOC and CDOM was observed when tributaries and mainstream
      are evaluated separately (Amazon River: N = 42, R2 = 0.74, p<0.05; CW: N = 13, R2
      = 0.57, p<0.05). However, this linear relationship was not observed during
      periods of higher rainfall and river discharge, requiring a specific model for
      these time periods to be developed (N = 25, R2 = 0.58, p<0.05). A strong linear
      positive relation was found between aCDOM(412) and pCO2(N = 69, R2 = 0.65,
      p<0.05) along the lower river. pCO2 was less affected by the optical difference
      between tributaries and mainstream waters or by the discharge conditions when
      compared to CDOM to DOC relationships. Including the river water temperature in
      the model improves our ability to estimate pCO2 (N = 69; R2 = 0.80, p<0.05). The
      ability to assess both DOC and pCO2 from CDOM optical properties opens further
      perspectives on the use of ocean colour remote sensing data for monitoring carbon
      dynamics in large running water systems worldwide.

PMID- 30114009
TI  - Snapshot multi-wavelength interference microscope.
AB  - A snapshot multi-wavelength interference microscope is proposed for high-speed
      measurement of large vertical range discontinuous microstructures and surface
      roughness. A polarization CMOS camera with a linear micro-polarizer array and
      Bayer filter accomplishes snapshot multi-wavelength phase-shifting measurement.
      Four interferograms with ??/2 phase shift are captured at each wavelength for
      phase measurement, the 2?? ambiguities are removed by using two or three
      wavelengths.

PMID- 30114007
TI  - Intron retention is a source of neoepitopes in cancer.
AB  - We present an in silico approach to identifying neoepitopes derived from intron
      retention events in tumor transcriptomes. Using mass spectrometry immunopeptidome
      analysis, we show that retained intron neoepitopes are processed and presented on
      MHC I on the surface of cancer cell lines. RNA-derived neoepitopes should be
      considered for prospective personalized cancer vaccine development.

PMID- 30114010
TI  - Design of an optical see-through light-field near-eye display using a discrete
      lenslet array.
AB  - In this paper, we propose a novel method to construct an optical see-through
      light-field near-eye display (OST LF-NED) by using a discrete lenslet array
      (DLA). The DLA is used as a spatial light modulator (SLM) to generate dense light
      field of three-dimensional (3-D) scenes inside the user's eyebox of the system
      and provide correct focus cues to the user. A corresponding light-field image
      rendering method is also proposed and demonstrated. The light emitted from the
      real objects passes through the transparent region of the display panel and the
      planar area of the DLA successively without redirection, so the user can have a
      clear view of the real scene as well as the virtual information. The stray light
      that may degrade the image quality has been analyzed in detail. The experimental
      result shows that the proposed method is capable of obtaining a corrected depth
      perception of the virtual information in augmented reality (AR) applications.

PMID- 30114011
TI  - 1.3 MUm InAs/GaAs quantum dot DFB laser integrated on a Si waveguide circuit by
      means of adhesive die-to-wafer bonding.
AB  - In this paper we report a single mode InAs/GaAs quantum dot distributed feedback
      laser at 1.3 MUm wavelength heterogeneously integrated on a Si photonics
      waveguide circuit. Single mode lasing around 1300 nm with a side-mode suppression
      ratio higher than 40 dB is demonstrated. High temperature operation with
      continuous wave lasing up to 100 degrees C is obtained. Threshold current
      densities as low as 205 A/cm2 were measured. These devices are attractive
      candidates to use in uncooled silicon photonic transceivers in data centers.

PMID- 30114012
TI  - All-inorganic perovskite quantum dots stabilized blue phase liquid crystals.
AB  - All-inorganic perovskite quantum dots (PQDs) have been effectively incorporated
      in the three-dimensional ordered structure of blue phase liquid crystals (BPLCs)
      to stabilize the BPLCs. Uniform dispersion, reduced phase transition temperature,
      widened BP temperature range, dynamic and fast electro-optical response and
      static optical display of selective reflection mode and photoluminescence mode
      have been confirmed with a given concentration of PQDs. Such a novel strategy of
      assembling all-inorganic PQDs in BPLCs shows favorable prospects for wide-range
      and near room temperature BPLCs, responsive BPLCs, multifunctional display
      materials and tunable bandgap lasers.

PMID- 30114013
TI  - Highly transmissive subtractive color filters based on an all-dielectric
      metasurface incorporating TiO2 nanopillars.
AB  - Transmissive subtractive color filters are proposed and demonstrated that take
      advantage of an all-dielectric metasurface based on a lattice of TiO2 nanopillars
      (NPs), rendering a high transmission efficiency that exceeds 90%. TiO2 NP
      elements have been created that exhibit a high aspect ratio. Specifically, a
      series of lithographic processes are conducted to form a narrow and deep hole in
      the photoresist, which is accompanied by atomic layer deposition of TiO2. A broad
      palette of vivid colors encompassing the visible band has been obtained by
      adjusting the NP diameter for a constant duty ratio of 0.35. For the NP
      resonator, the electric and magnetic field profiles in conjunction with the
      scattering cross-sections have been meticulously investigated to theoretically
      validate that the resonant transmission dips are primarily governed by the
      simultaneous excitation of an electric dipole and a magnetic dipole via Mie
      scattering.

PMID- 30114014
TI  - High repetition-rate femtosecond stimulated Raman spectroscopy with fast
      acquisition.
AB  - Time-resolved femtosecond stimulated Raman spectroscopy (FSRS) is a powerful tool
      for investigating ultrafast structural and vibrational dynamics in light
      absorbing systems. However, the technique generally requires exposing a sample to
      high laser pulse fluences and long acquisition times to achieve adequate signal
      to-noise ratios. Here, we describe a time-resolved FSRS instrument built around a
      Yb ultrafast amplifier operating at 200 kHz, and address some of the unique
      challenges that arise at high repetition-rates. The setup includes detection with
      a 9 kHz CMOS camera and an improved dual-chopping scheme to reject scattering
      artifacts that occur in the 3-pulse configuration. The instrument demonstrates
      good signal-to-noise performance while simultaneously achieving a 3-6 fold
      reduction in pulse energy and a 5-10 fold reduction in acquisition time relative
      to comparable 1 kHz instruments.

PMID- 30114015
TI  - Simultaneous implementation of enhanced resolution and large dynamic range for
      fiber temperature sensing based on different optical transmission mechanisms.
AB  - In this paper, a high resolution and large dynamic range fiber optic temperature
      sensor without measurement crosstalk has been proposed. Two combinational
      mechanisms of anti-resonant reflecting optical waveguide and inline Mach-Zehnder
      interference structure are integrated in single hole twin eccentric cores fiber.
      The dual-effect composite spectrum is consist of several dominant resonant
      wavelengths and comb pattern, which are corresponding to the two above-mentioned
      mechanisms. Gauss fit and fast Fourier transform filtering are used for
      extracting the resonant wavelengths and comb spectrum, respectively. Accordingly,
      the temperature sensitivity of 42.18pm/ degrees C and 2.057nm/ degrees C are
      achieved by tracking the coherent decrease point. The lower sensitivity can
      guarantee a large dynamic range, while the higher one will contribute to the
      enhanced resolution. Therefore, the temperature monitoring is the combination of
      large dynamic range and enhanced resolution. Moreover, the size of the
      ultracompact sensor is only 950MUm, which has a great potential for engineering
      applications.

PMID- 30114016
TI  - Color-tunable organic light-emitting diodes with vertically stacked blue, green,
      and red colors for lighting and display applications.
AB  - We demonstrate independently and simultaneously controlled color-tunable organic
      light-emitting diodes (OLEDs) with vertically stacked blue, green, and red
      elements. The blue, green, and red elements were placed at the bottom, middle,
      and top positions, respectively, forming color-tunable OLEDs. The independently
      driven blue, green, and red elements in the color-tunable OLEDs exhibited low
      driving voltages of 5.3 V, 3.0 V, and 4.6 V, as well as high external quantum
      efficiencies of 11.1%, 10.9%, and 9.6%, respectively, at approximately 1000
      cd/m2. Each element in the color-tunable OLEDs showed high-purity blue, green,
      and red colors with little parasitic emission owing to the delicately designed
      device structure resultant from optical simulations. The color-tunable OLEDs
      could produce any colors inside the triangle formed with blue (0.136, 0.261),
      green (0.246, 0.697), and red (0.614, 0.386) Commission Internationale de
      l'eclairage (CIE) 1931 color coordinates. In addition, the correlated color
      temperatures (CCTs) of white colors in the color-tunable OLED can be easily
      changed from the warm white to the cool white by controlling the red, green, and
      blue emissions simultaneously. The white colors in the color-tunable OLED have
      the CIE 1931 color coordinate of (0.304, 0.351), with a CCT of 6289 K and (0.504,
      0.440), with a CCT of 2407K at the driving voltage of 5 V (blue), 2.8 V (green),
      4.4 V (red), and 4.6 V (blue), 3 V (green), 5 V (red), respectively. Furthermore,
      the white color in the color-tunable OLED exhibited a high color rendering index
      (~88.7) due to vertically stacked three color system. Moreover, we successfully
      fabricated a large-sized, 14 * 12 pixel array of the color-tunable OLEDs to
      demonstrate lighting and display applications, respectively.

PMID- 30114017
TI  - Experimental demonstration of adaptive VFF-RLS-FDE for long-distance mode
      division multiplexed transmission.
AB  - We experimentally demonstrate adaptive variable-forgetting-factor (VFF) recursive
      least-square frequency-domain equalization (RLS-FDE) for mode-division
      multiplexing. The VFF-RLS-FDE algorithm improves convergence speed as
      transmission distance increases. For MDM transmission over a 1,000-km few-mode
      fiber, the convergence speed was increased by 18.7 times in comparison with LMS
      FDE. In the meantime, the convergence error performance of VFF-RLS is also much
      superior to LMS while fixed-forgetting-factor RLS has a 0.2 dB penalty compared
      with LMS. The proposed VFF-RLS algorithm achieves better performances than
      conventional RLS in terms of convergence speed and convergence error.

PMID- 30114019
TI  - Femtosecond pulse and terahertz two-tone generation from facet-free multi-segment
      laser diode in InP-based generic foundry platform.
AB  - In this paper, a monolithically integrated ~1.55 um semiconductor laser in the
      fourth harmonic colliding pulse mode locking configuration is reported. This
      device was developed within a multi-project wafer run at an InP-based active
      passive generic foundry. The 1.66-mm Fabry-Perot cavity is formed with two on
      chip reflector building blocks rather than cleaved facets. In the cavity, three
      absorber sections symmetrically divide the cavity in four gain segments. This
      laser diode is able to emit 100-GHz pulse trains with 500-fs pulse duration as
      well as two-tone emissions with a frequency separation of 2.7 THz. The dependence
      of the spectral behavior on the forward bias current for gain sections and the
      reverse bias voltage for absorber sections are experimentally demonstrated.

PMID- 30114018
TI  - Depth of field extension and objective space depth measurement based on wavefront
      imaging.
AB  - When all the parts of the wavefront imaging system are kept static after
      wavefront measuring, the target's images are blurry, because the depth of field
      (DOF) of the system affects the imaging quality. In this paper, the method for
      extending the DOF of the wavefront imaging system through an integrated
      architecture of a liquid-crystal microlens array (LCMLA) powered by electricity
      and a common photosensitive array, is presented. The DOF can be extended
      remarkably only by stitching together several sub-images of the LCMLA. The
      problem that the wavefronts and imaging results are insensitive to the objective
      depth is also solved. Optimal driving voltage signals are found out according to
      Sobel mean gradient to efficiently calibrate the depth of objective space in
      order to quantitatively measure the depth. The approach indicates a viable way to
      effectively extend the DOF of imaging micro-systems and to measure the
      geometrical depth of targets at the same time.

PMID- 30114020
TI  - Tunable optical-microwave filters optimized for 100 MHz resolution.
AB  - New continuously tunable RF-spectrum analyzers, RF receivers, and RF signal
      generators are proposed and analyzed for the silicon-on-insulator integrated
      photonic platform at the ~1550 nm wavelength. These RF system-on-a-chip
      applications are enabled by a new narrowband 2x2 Mach-Zehnder interferometer
      (MZI) tuned filters for reconfigurable multiplexing, demultiplexing and RF
      channel selection. The filter can be optimized for ~100 MHz 3-dB bandwidth (BW)
      by utilizing N closely coupled Bragg-grating resonators to form one effective
      waveguide resonator in the single-mode silicon nanowire used for each MZI arm.
      The number of periods M within each individual resonator is selected to engineer
      BW in the 0.1 to 1 GHz range. Butterworth design is employed. Continuous tuning
      of the 100 MHz-BW devices over 18.6 GHz has been simulated by using local micron
      scale thermo-optical heater stripes on the MZI arms with a temperature rise from
      0 to 48K. For the case of N = 3 and 100-nm silicon side teeth, some
      representative performance predictions are: insertion loss (IL) = -10.7 dB, BW =
      80.5 MHz and L = 113 MUm for M = 58; while IL = -0.74 dB, BW = 1210 MHz and L =
      86 MUm for M = 44.

PMID- 30114021
TI  - Simulation of internal stress waves generated by laser-induced damage in
      multilayer dielectric gratings.
AB  - Multilayer dielectric (MLD) gratings used in ultrahigh-intensity laser systems
      often exhibit a laser-induced damage performance below that of their constituent
      materials. Reduced performance may arise from fabrication- and/or design-related
      issues. Finite element models were developed to simulate stress waves in MLD
      grating structures generated by laser-induced damage events. These models
      specifically investigate the influence of geometric and material parameters on
      how stress waves can lead to degradation of material structural integrity that
      can have adverse effects on its optical performance under subsequent laser
      irradiation: closer impedance matching of the layer materials reduces maximum
      interface stresses by ~20% to 30%; increasing sole thickness from 50 nm to 500 nm
      reduces maximum interface stresses by ~50%.

PMID- 30114022
TI  - Phase-resolved terahertz self-detection near-field microscopy.
AB  - At terahertz (THz) frequencies, scattering-type scanning near-field optical
      microscopy (s-SNOM) based on continuous wave sources mostly relies on cryogenic
      and bulky detectors, which represents a major constraint for its practical
      application. Here, we devise a THz s-SNOM system that provides both amplitude and
      phase contrast and achieves nanoscale (60-70nm) in-plane spatial resolution. It
      features a quantum cascade laser that simultaneously emits THz frequency light
      and senses the backscattered optical field through a voltage modulation induced
      inherently through the self-mixing technique. We demonstrate its performance by
      probing a phonon-polariton-resonant CsBr crystal and doped black phosphorus
      flakes.

PMID- 30114023
TI  - Characterization of an imaging multimode optical fiber using a digital micro
      mirror device based single-beam system.
AB  - This work demonstrates experimental approaches to characterize a single multimode
      fiber imaging system without a reference beam. Spatial light modulation is
      performed with a digital micro-mirror device that enables high-speed binary
      amplitude modulation. Intensity-only images are recorded by the camera and
      processed by a Bayesian inference based algorithm to retrieve the phase of the
      output optical field as well as the transmission matrix of the fiber. The
      calculated transmission matrix is validated by three standards: prediction
      accuracy, transmission imaging, and focus generation. Also, it is found that
      information on mode count and eigenchannels can be extracted from the
      transmission matrix by singular value decomposition. This paves the way for a
      more compact and cheaper single multimode fiber imaging system for many demanding
      imaging tasks.

PMID- 30114024
TI  - High-efficiency energy transfer in perovskite heterostructures.
AB  - Here, we report the energy transfer in (PEA)2PbI4/MAPbBr3 perovskite
      heterostructures. Under two-photon excitation, the photoluminescence (PL)
      emission of the (PEA)2PbI4 flake is nearly completely quenched, while that of the
      MAPbBr3 microplate is greatly increased (6.5 folds higher) in the
      heterostructure. The opposite variation character of the PL emissions is
      attributed to the radiative energy transfer from the (PEA)2PbI4 flake to the
      MAPbBr3 microplate. The radiative energy transfer occurs on an ultrafast
      timescale with a high efficiency (~100%). In addition, a strongly thickness- and
      wavelength-dependent interlayer interaction is observed under one-photon
      excitation. This work advocates great promise for revealing the interlayer
      interaction of perovskite heterostructures and developing high-performance
      optoelectronic devices.

PMID- 30114025
TI  - Fiber-distributed ultra-wideband radar network based on wavelength reusing
      transceivers.
AB  - A fiber-distributed ultra-wideband (UWB) radar network based on wavelength
      reusing transceivers is proposed and demonstrated. In the proposed system,
      wavelength-division multiplexing technology is applied to connect a central unit
      (CU) and several spatially separated transceivers. The optically generated UWB
      pulses in different transceivers are designed to have different polarities or
      shapes, so the CU can easily identify which transceiver the echo UWB pulse is
      emitted from. By applying the wavelength reusing, the wavelength of the uplink
      UWB pulse can also be used by the CU to identify which transceiver it is received
      by. Therefore, with very simple cooperative signal processing in the CU, the
      information of the target in the radar detection area can be extracted. In
      addition, because the fiber lengths in the network are known, clock
      synchronization in the transceivers is not required, which simplifies further the
      entire system. In an experiment, 2-D localization with localization accuracy of
      about one centimeter is achieved using the proposed radar network with two
      distributed transceivers.

PMID- 30114026
TI  - Novel concept for visible and near infrared spectro-interferometry: laser-written
      layered arrayed waveguide gratings.
AB  - With the growing complexity of astronomical instruments devoted to
      interferometry, such as MATISSE (a 4 telescope beam combiner) or FIRST (a 9 sub
      apertures beam combiner), and the rebirth of space projects such as LIFE (a mid
      infrared interferometer), integrated optics devices can be an interesting and
      complementary approach for beam combination of a large number of apertures.
      Moreover, one of the approaches for beam combination is pairwise combination of
      the inputs (either from individual telescopes or from aperture masking on a
      single telescope), which scales as N(N-1)/2 for an N input system. Astrophotonics
      devices are attractive to reduce mass and system complexity, while achieving all
      the beam combination in a single chip, even for a high number of inputs. The aim
      of this work is to develop a compact photonic device for astronomical
      applications and demonstrate a proof-of-concept of a spectro-interferometer. In
      this paper ultrafast laser inscription is used to fabricate three arrayed
      waveguide gratings (AWGs) stacked vertically. This arrangement enables spectral
      dispersion and interferometry to be measured simultaneously. Individual AWGs were
      designed for operation at 633 nm, and demonstrated at 633nm and 830nm. A scan
      between 790 and 830nm was also achieved to study the wavelength behavior of the
      AWG. Using a segmented mirror, light at 633nm or 830nm was injected
      simultaneously into three AWGs layered 40 um apart, showing analogous behavior
      for all three layers and no unexpected crosstalk. Finally the three outputs were
      vertically combined to obtain interference fringes, showing the feasibility of
      spectro-interferometry and opening the way for compact astrophotonic devices
      devoted to phase closure studies, used in astronomy to reduce the effect of
      atmospheric turbulence.

PMID- 30114027
TI  - Ultrafast optical properties of type-II CdZnS/ZnSe core-shell quantum dots.
AB  - In this study, the ultrafast optical properties of type-II CdZnS/ZnSe core-shell
      quantum dots were investigated using the Z-scan and transient absorption
      technique with femtosecond pulses. With 800-nm wavelength excitation, the
      CdZnS/ZnSe quantum dots exhibited two-photon absorption, and the two-photon
      absorption cross section was obtained as about 3.37 * 106 GM. In addition, the
      transfer time of electrons and the recombination lifetime of a single exciton
      were obtained. For the photoluminescence of the CdZnS/ZnSe quantum dots at
      temperatures from 80 to 280 K, the peak position redshifted by 60 meV, width
      broadened by 3 meV, and intensity decreased by a factor of four.

PMID- 30114028
TI  - Sub-shot-noise-limited phase estimation via SU(1,1) interferometer with thermal
      states.
AB  - We theoretically study the phase sensitivity of an SU(1,1) interferometer with a
      thermal state and a squeezed vacuum state as inputs and parity detection as the
      measurement. We find that the phase sensitivity can beat the shot-noise limit and
      approaches the Heisenberg limit, with increasing input photon number, in an ideal
      situation. We also consider the effect of various noises, including photon loss,
      dark counts, and thermal photon noise. Our results show that the phase
      sensitivity is below the shot-noise limit with photon loss and dark counts, but
      cannot beat the shot-noise limit in the presence of thermal noise.

PMID- 30114029
TI  - High-power passively Q-switched 2.0 MUm all-solid-state laser based on a MoTe2
      saturable absorber.
AB  - In this article, a high-power diode-end-pumped passively Q-switched (PQS) Tm:YAP
      laser is reported with novel two-dimension (2D) molybdenum ditelluride (MoTe2) as
      a saturable absorber (SA). By using the open-aperture Z-scan method, the
      saturable absorption properties around 2.0 MUm was characterized with a saturable
      fluence of 2.26 MUJ/cm2 and a modulation depth of 6.0% for the as-prepared MoTe2
      SA. The band structure of MoTe2 with the introduction of Te vacancies is
      simulated by the DFT method, and the results indicate that the bandgap can be
      reduced with the vacancies in a suitable range. The shortest pulse width of 380
      ns was obtained with an average output power of 1.21 W at a repetition rate of
      144 kHz, corresponding to a maximum single pulse energy of 8.4 uJ and peak power
      of 22.2 W. It is the first presentation of MoTe2 as the saturable absorber in 2.0
      MUm solid-state pulse laser generation and the pulse width is the shortest among
      2.0 MUm solid-state lasers passive Q-switched with transitional metal
      dichalcogenides (TMDs) SAs to the best of our knowledge. The results indicated
      that MoTe2 should be an excellent optical modulator for high repetition rate and
      short pulsed laser generation in a broadband spectral range.

PMID- 30114030
TI  - Holographically controlled three-dimensional atomic population patterns.
AB  - The interaction of spatially structured light fields with atomic media can
      generate spatial structures inscribed in the atomic populations and coherences,
      allowing for example the storage of optical images in atomic vapours. Typically,
      this involves coherent optical processes based on Raman or EIT transitions. Here
      we study the simpler situation of shaping atomic populations via spatially
      dependent optical depletion. Using a near resonant laser beam with a
      holographically controlled 3D intensity profile, we imprint 3D population
      structures into a thermal rubidium vapour. This 3D population structure is
      simultaneously read out by recording the spatially resolved fluorescence of an
      unshaped probe laser. We find that the reconstructed atomic population structure
      is largely complementary to the intensity structure of the control beam, however
      appears blurred due to global repopulation processes. We identify and model these
      mechanisms which limit the achievable resolution of the 3D atomic population. We
      expect this work to set design criteria for future 2D and 3D atomic memories.

PMID- 30114031
TI  - Inter-polarization mixers for coherent detection of optical signals.
AB  - Electro-magnetic (EM) mixers are fundamental building blocks in communication
      systems. They are used in frequency/wavelength filters, interferometric
      modulators, amplitude-phase receivers, to name a few. Traditional EM mixers have
      two or more input ports and work only for co-polarized signal and local
      oscillator (LO) incident on its inputs. Here we report on novel designs, in
      silicon, of inter-polarization EM mixers operating at 1550 nm wavelength. The 180
      degree optical mixer comprising a single input port is demonstrated to coherently
      mix orthogonally polarized signal and LO. Using the proposed 180-degree mixer, we
      report on a novel design for a 90-degree optical mixer on silicon with small
      footprint, broadband response, low loss and good fabrication tolerance. It
      exploits birefringence of a waveguide to achieve broadband and fabrication
      tolerant 90 degrees  phase difference between the signal/LO relative phase in the
      in-phase and quadrature components. A monolithic silicon photonics coherent
      receiver is demonstrated using the reported 90-degree mixer, and its operation at
      22 Gbaud and 44 Gbaud is shown. These mixers pave the way for novel coherent
      receiver architectures in long-haul, metro, passive optical networks and data
      center interconnect applications.

PMID- 30114032
TI  - Realizing frequency controlled wide-angle beam scanning with an artificial
      electromagnetic structure in the terahertz band.
AB  - In this paper, an approach to achieve wide-angle beam scanning in the terahertz
      (THz) band with frequency sweeping was proposed based on a metasurface structure.
      To widen the scanning angular scope, a coherent enhancement mechanism for
      improving the mode competition efficiency of the high-order diffraction mode was
      first implemented. A systematic method was firstly developed for the design of
      practical frequency-controlled beam scanning quasi-optics in THz band, in which
      the optimization of scanning range, linearity, and the avoidance of beam blocking
      are comprehensively considered. The proposed concept and approach was verified by
      the measured wide-angle beam scanning at the 0.18-0.22THz frequency band, with a
      diffraction efficiency of the main lobe as high as 88 percent. The good
      performance of the device paves the way for potential applications in THz
      imaging, moving target detection, and communication.

PMID- 30114034
TI  - Deterministic generation of single soliton Kerr frequency comb in microresonators
      by a single shot pulsed trigger.
AB  - Kerr soliton frequency comb generation in monolithic microresonators recently
      attracted great interests as it enables chip-scale few-cycle pulse generation at
      microwave rates with smooth octave-spanning spectra for self-referencing. Such
      versatile platform finds significant applications in dual-comb spectroscopy, low
      noise optical frequency synthesis, coherent communication systems, etc. However,
      it still remains challenging to straightforwardly and deterministically generate
      and sustain the single-soliton state in microresonators. In this paper, we
      propose and theoretically demonstrate the excitation of single-soliton Kerr
      frequency comb by seeding the continuous-wave driven nonlinear microcavity with a
      pulsed trigger. Unlike the mostly adopted frequency tuning scheme reported so
      far, we show that an energetic single shot pulse can trigger the single-soliton
      state deterministically without experiencing any unstable or chaotic states.
      Neither the pump frequency nor the cavity resonance is required to be tuned. The
      generated mode-locked single-soliton Kerr comb is robust and insensitive to
      perturbations. Even when the thermal effect induced by the absorption of the
      intracavity light is taken into account, the proposed single pulse trigger
      approach remains valid without requiring any thermal compensation means.

PMID- 30114033
TI  - Extremely broadband ultralight thermally-emissive optical coatings.
AB  - We report the design, fabrication, and characterization of ultralight highly
      emissive structures with a record-low mass per area that emit thermal radiation
      efficiently over a broad spectral (2 to 30 microns) and angular (0-60 degrees )
      range. The structures comprise one to three pairs of alternating metallic and
      dielectric thin films and have measured effective 300 K hemispherical emissivity
      of 0.7 to 0.9 (inferred from angular measurements which cover a bandwidth
      corresponding to 88% of 300K blackbody power). To our knowledge, these micron
      scale-thickness structures, are the lightest reported optical coatings with
      comparable infrared emissivity. The superior optical properties, together with
      their mechanical flexibility, low outgassing, and low areal mass, suggest that
      these coatings are candidates for thermal management in applications demanding of
      ultralight flexible structures, including aerospace applications, ultralight
      photovoltaics, lightweight flexible electronics, and textiles for thermal
      insulation.

PMID- 30114035
TI  - Routes of odd-even harmonic emission from oriented polar molecules.
AB  - We study odd-even high-harmonic generation (HHG) from oriented asymmetric
      molecules with different symmetries in strong laser fields. A model based on
      strong-field approximations is used which allows us to resolve the contributions
      of different emission routes to odd-even HHG. The comparison between the HHG
      yields of all routes versus one certain route demonstrates that the routes in
      which the electron ionizes from the gerade component of the asymmetric orbital
      contribute mainly to odd-even HHG. We show that the potential mechanism is
      associated with effects of intramolecular interference in tunneling ionization as
      the bound electron passes through the barrier formed by the laser field and the
      asymmetric Coulomb potential. The influences of different emission routes on
      asymmetric orbital imagining with odd-even HHG are also addressed.

PMID- 30114036
TI  - Illumination uniformity improvement in digital micromirror device based scanning
      photolithography system.
AB  - Illumination uniformity in photolithography systems determines the dimensional
      difference across the entire lithographic substrate. However, traditional
      lithography system relies on expensive and complex illumination system for
      achieving uniform illumination. In this paper, we propose a simple and cost
      effective method based on the modulation of digital micromirror device to improve
      illumination uniformity. The modulation according to a digital mask achieved via
      an iteration program improves the uniformity to be above 95%. We demonstrate the
      effectiveness of the method by experimentally fabricating a linear grating. By
      implementing this method, the maximum dimensional difference is decreased from
      3.3MUm to 0.3MUm. Further simulations indicate that higher uniformity is
      achievable once the field of view on the DMD is divided into smaller subregions.

PMID- 30114037
TI  - Dynamic morphing of 3D curved laser traps for all-optical manipulation of
      particles.
AB  - The development of optical manipulation techniques focused on the confinement and
      transport of micro/nano-particles has attracted increased interest in the last
      decades. In particular the combination of all-optical confinement and propelling
      forces, respectively arising from high intensity and phase gradients of a
      strongly focused laser beam, is promising for optical transport. The recently
      developed freestyle laser trap exploits this manipulation mechanism to achieve
      optical transport along arbitrary 3D curves. In practice, reconfigurable 3D
      optical transport of numerous particles is a challenging problem because it
      requires the ability to easily adapt the trajectory in real time. In this work,
      we introduce and experimentally demonstrate a strategy for on-task adaptive
      design of freestyle laser traps based on a dynamic morphing technique. This
      provides programmable smooth transformation of the 3D shape of the curved laser
      trap with independent control of the propelling forces along it, that can be
      configured according to the considered application. Dynamic morphing, proven here
      on the example of colloidal dielectric micro-particles, significantly simplifies
      the important problem of real-time reconfigurable 3D optical transport and opens
      up routes for other sophisticated optical manipulation tasks.

PMID- 30114038
TI  - Oblique incidence of semi-guided planar waves on slab waveguide steps: effects of
      rounded edges.
AB  - Oblique propagation of semi-guided waves across slab waveguide structures with
      bent corners is investigated. A critical angle can be defined beyond which all
      radiation losses are suppressed. Additionally an increase of the curvature radius
      of the bends also leads to low-loss configurations for incidence angles below
      that critical angle. A combination of two bent corner systems represents a step
      like structure, behaving like a Fabry-Perot interferometer, with two partial
      reflectors separated by the vertical height between the horizontal slabs. We
      numerically analyse typical high-index-contrast Si/SiO2 structures for their
      reflectance and transmittance properties. When increasing the curvature radius
      the resonant effect becomes less relevant such that full transmittance is reached
      with less critical conditions on the vertical distance or the incidence angle.
      For practical interest 3-D problems are considered, where the structures are
      excited by the fundamental mode of a wide, shallow rib waveguide. High
      transmittance levels can be observed also for these 3-D configurations depending
      on the width of the rib.

PMID- 30114039
TI  - Index for the evaluation of the general photometric performance of photometers.
AB  - The General V(lambda) Mismatch Index, f1 ', was defined for a general description
      of the photometric performance of photometers. This index is widely-used in
      photometry, and it is very relevant for selecting photometers for low-uncertainty
      photometric measurements. It quantifies the spectral mismatch between the
      relative spectral responsivity of a photometer and the luminous efficiency
      function for photopic vision, V(lambda). The linear correlation between the real
      general photometric measurement error and f1 ' of 77 photometers was studied for
      four sets of light sources: R, G and B LEDs (narrowband spectral power
      distributions, SPDs), blackbodies at different colour temperatures (broadband
      SPDs), phosphor-based LEDs at different correlated color temperatures (SPDs with
      narrow- and broad-band features), and a mixture of blackbodies and phosphor-based
      LED sources. This article shows that it can be defined an alternative index which
      is notably better correlated with the real general photometric measurement error
      of the photometers under light sources with broadband features in their SPDs,
      adequate for general lighting. This index is based on filtering the high spectral
      frequencies variations between the relative spectral responsivity of the
      photometer and V(lambda). The use of this new index for the assessment of the
      general photometric performance of photometers would improve the selection of
      high quality photometers and, consequently, would contribute to the general
      improvement of photometric measurements.

PMID- 30114040
TI  - Probing vectorial near field of light: imaging theory and design principles of
      nanoprobes.
AB  - Near-field microscopy is widely used for characterizing electromagnetic fields at
      nanoscale, where nanoprobes afford the opportunity to extract subwavelength
      optical quantities, including the amplitude, phase, polarization, chirality, etc.
      However, owing to the complexity of various nanoprobes, a general and intuitive
      theory is highly desired to assess the vectorial responses of nanoprobes and
      interpret the mechanism of the probe-field interaction. Here, we develop a
      general imaging theory based on the reciprocity of electromagnetism and multipole
      expansion analysis. The proposed theory closely resembles the multipolar
      Hamiltonian for light-matter interaction energy, revealing the coupling mechanism
      of the probe-field interaction. Based on this theory, we introduce a new paradigm
      for the design of functional nanoprobes by analyzing the reciprocal dipole
      moments, and establish effective design principles for the imaging of vectorial
      near fields. As application examples of the proposed theory, we numerically
      analyze the responses of two typical probes, a split-ring probe and a
      nanoparticle probe, which can quantitatively reproduce and well explain the
      experimental results of previously reported measurements of the optical magnetism
      and the transverse spin angular momentum. Our work provides a powerful tool for
      the design and analysis of new functional probes that may enable the probing of
      various physical quantities of the vectorial near field.

PMID- 30114041
TI  - Picosecond-pulsed laser ablation of zinc: crater morphology and comparison of
      methods to determine ablation threshold.
AB  - Ablation of bulk polycrystalline zinc in air is performed with single and
      multiple picosecond laser pulses at a wavelength of 1030 nm. The relationships
      between the characteristics of the ablated craters and the processing parameters
      are analyzed. Morphological changes of the ablated craters are characterized by
      means of scanning electron microscopy and confocal laser scanning microscopy.
      Chemical compositions of both the treated and untreated surfaces are quantified
      with X-ray photoelectron spectroscopy. A comparative analysis on the
      determination of the ablation threshold using three methods, based on ablated
      diameter, depth and volume is presented along with associated incubation
      coefficients. The single pulse ablation threshold value is found to equal 0.21
      J/cm2. Using the calculated incubation coefficients, it is found that both the
      fluence threshold and energy penetration depth show lesser degree of incubation
      for multiple laser pulses.

PMID- 30114042
TI  - Intelligent adaptive coherent optical receiver based on convolutional neural
      network and clustering algorithm.
AB  - In a cognitive, heterogeneous, optical network, it would be important to identify
      physical layer information, especially the modulation formats of transmitted
      signals. The modulation format information is also indispensable for carrier
      phase-recovery in a coherent optical receiver. Because constellation diagrams of
      modulation signals are susceptible to various noises, we utilize a convolutional
      neural network to process the amplitude data after the modulation-format-agnostic
      clock recovery. Furthermore, for the carrier-phase-recovered data, we use the
      clustering method based on a fast search and find the density peaks to classify
      the constellation clusters and use the k-nearest-neighbor method to label the
      samples. The proposed receiver system has a simple architecture to identify the
      modulation format based on the amplitude information and can track fast changes
      of the signals to improve the accuracy of the symbol decision. We have
      demonstrated this experimentally and have achieved remarkable BER improvement.

PMID- 30114043
TI  - Laser frequency instability of 2 * 10-16 by stabilizing to 30-cm-long Fabry-Perot
      cavities at 578 nm.
AB  - Laser light at 578 nm is frequency-stabilized to two independent 30-cm-long Fabry
      Perot cavities. To achieve a thermal-noise-limited cavity length stability, the
      geometry and support configuration of the Fabry-Perot cavities are optimized. The
      fractional frequency instability of each cavity-stabilized laser system is 2 * 10
      16 at 1 s averaging time, approaching to the thermal-noise-induced length
      instability of the reference cavity. The most probable linewidth of each laser
      system is about 0.2 Hz, and the laser frequency noise at Fourier frequency of 1
      Hz is 0.1 Hz/?Hz.

PMID- 30114044
TI  - Partially etched chirped fiber Bragg grating (pECFBG) for joint temperature,
      thermal profile, and refractive index detection.
AB  - In this work, a partially etched chirped fiber Bragg grating (pECFBG) is
      introduced, as a compact sensor for multi-parametric measurement of temperature,
      thermal gradients over the active length, and refractive index. The sensor is
      fabricated by wet-etching a portion of a 14-mm linearly chirped FBG with linear
      chirp profile. The resulting device has two active areas: the unetched part of
      the grating (2 mm) can be used either as a uniform temperature sensor, or to
      detect thermal gradients experienced through the grating length by means of a
      spectral reconstruction technique; the etched part (12 mm), besides having a
      similar thermal sensitivity, is exposed to refractive index sensing through the
      introduction of a sensitivity to external refractive index. Overall, the pECFBG
      structure behaves as a compact sensor with multi-parameter capability, that can
      both measure temperature and refractive index on the same grating, but also
      spatially resolve temperature detection through the grating section. The results
      have been validated through both a model and experimental setup, showing that the
      mutual correlation algorithm applied to different spectral parts of the grating
      is able to discriminate between uniform and gradient-shaped temperature profiles,
      and refractive index changes.

PMID- 30114045
TI  - Dynamic control of cylindrical vector beams via anisotropy.
AB  - We demonstrate that the spatially diffractive properties of cylindrical vector
      beams could be controlled via linear interactions with anisotropic crystals. It
      is the first time to show experimentally that the diffraction of the vector beams
      can be either suppressed or enhanced significantly during propagation, depending
      on the sign of anisotropy. Importantly, it is also possible to create a linear
      non-spreading and shape-preserving vector beam, by vanishing its diffraction
      during propagation via strong anisotropy in a crystal. The manageable diffractive
      effect enables manipulating propagation dynamics of the circular Airy vector
      beams, i.e., their propagation trajectories can be dynamically controlled by
      weakening or enhancing self-acceleration of the Airy beam. We further demonstrate
      that the cylindrical vector beams with initially zero orbital angular momentum
      can be rotated either clockwise or anticlockwise, relying on the sign of the
      anisotropy.

PMID- 30114046
TI  - High transparent mid-infrared silicon "window" decorated with amorphous photonic
      structures fabricated by facile phase separation.
AB  - High transparency in the infrared (IR) region is desirable for most common IR
      materials and devices, due to their high interfacial reflectance, resulting from
      the high refractive indices of constituent substances. Herein, a new strategy,
      with using phase-separated polystyrene (PS)/polymethylmethacrylate (PMMA) blends
      as masks, is proposed to fabricate subwavelength structures for Si with
      significantly enhanced mid-IR transmission. Maximum transmittance approaching to
      70% and 90% are achieved with single and double- side structured Si respectively.
      The fabricated subwavelength structures are short-range ordered amorphous
      photonic structures (APSs). By using different spin-coating speeds and molar
      ratios of PS to PMMA and by adjusting the etching duration time, tunable enhanced
      transmission are also obtained. The good performance of high transmission is
      confirmed by mid-IR thermal imaging experiments. Furthermore, the enhanced
      transmission is effective over a wide range of incident angles up to 50 degrees 
      and well maintained at high temperatures up to 600  degrees C.

PMID- 30114047
TI  - DD-OFDM transmission over few-mode fiber based on direct vector mode
      multiplexing.
AB  - The fiber vector eigenmode based mode division multiplexing (VMDM) transmission
      over few-mode fiber (FMF) with the 1st-order cylinder vector beams (CVBs) has
      been demonstrated. The performances of generated CVB using q-plate (QP) have been
      characterized before and after transmission over the FMF respectively based on
      the high-order Poincare sphere model and polarization grating (PG). The measured
      minimum mode isolations between the two CVBs (TM01 and TE01 modes) of the used 4
      mode FMF are about 16.8 dB after transmitting over 5 m and 12.5 dB over 100 m
      respectively. Then the dual-vector-mode-multiplexed transmissions over FMF of 96
      Gb/s with length of 5m and 48 Gb/s of 100 m have been realized in combination
      with the modulation of direct-detection (DD) orthogonal-frequency-division
      multiplexing (OFDM) without using multiple-input multiple-output (MIMO) digital
      signal processing (DSP). The experimental results indicate that the CVB-based
      technology could find the potential in large-capacity short-reach optical
      interconnects.

PMID- 30114048
TI  - Dual-beam manually actuated distortion-corrected imaging (DMDI): two dimensional
      scanning with a single-axis galvanometer.
AB  - We recently demonstrated a new two-dimensional imaging paradigm called dual-beam
      manually actuated distortion-corrected imaging (DMDI). This technique uses a
      single mechanical scanner and two spatially separated beams to determine relative
      sample velocity and simultaneously corrects image distortions due to manual
      actuation. DMDI was first demonstrated using a rotating dual-beam micromotor
      catheter. Here, we present a new implementation of DMDI using a single axis
      galvanometer to scan a pair of beams in approximately parallel lines onto a
      sample. Furthermore, we present a method for automated distortion correction
      based on frame co-registration between images acquired by the two beams.
      Distortion correction is possible for manually actuated motion both perpendicular
      and parallel to the galvanometer-scanned lines. Using en face OCT as the imaging
      modality, we demonstrate DMDI and the automated distortion correction algorithm
      for imaging a printed paper phantom, a dragon fruit, and a fingerprint.

PMID- 30114049
TI  - Fully degeneracy-lifted bow-tie elliptical ring-core multi-mode fiber.
AB  - We present a bow-tie elliptical ring-core multi-mode fiber (BT-ERC-MMF) that
      features an elliptical ring-core structure and two symmetrical bow-tie stress
      applying parts (SAPs). This special fiber design breaking geometry and stress
      symmetry fully separates the two- or four-fold degenerate modes in traditional
      circular symmetry fiber with strong mode coupling during mode-division
      multiplexing (MDM) transmission. The designed fiber is able to support 53 fully
      degeneracy-lifted eigenmodes with minimum effective index difference between
      adjacent modes larger than 1.59 * 10-4 at 1550 nm, facilitating potential fiber
      eigenmode multiplexing transmission without using multiple-input multiple-output
      digital signal processing (MIMO-DSP) technique. The effect of bending on the
      designed fiber is investigated based on conformal mapping. Broadband performance
      including effective modal index (neff), effective index difference (Deltaneff),
      effective mode area (Aeff), nonlinearity and chromatic dispersion (D) is also
      comprehensively studied over the whole C band ranging from 1530 to 1565 nm. The
      designed fiber targets emerging applications in low-crosstalk direct fiber
      eigenmode-division multiplexing combined with the mature wavelength-division
      multiplexing (WDM) technique to increase transmission capacity and spectral
      efficiency.

PMID- 30114050
TI  - Theoretical and experimental investigation of polarization coexistence and
      switching in an optical bistability Tm,Ho:LLF laser.
AB  - We first investigate the polarization coexistence and switching between the
      orthogonal pi- and sigma-polarization states in a free running optical
      bistability Tm,Ho:LLF laser. The output performances of the optical bistability
      Tm,Ho:LLF laser is numerically simulated, based on a new rate equation theory
      model taking into account the influences of polarization-dependent gain and
      losses. The simulation results show the polarization coexistence and switching of
      output laser in the process of decreasing pump power. The physical mechanism of
      polarization coexistence and switching is clarified by analyzing the polarization
      dependent net-gain coefficients. Furthermore, the polarization coexistence and
      switching are experimentally realized in the optical bistability Tm,Ho:LLF laser,
      which validates the theoretical analysis. The theoretical model can be applied to
      analyze the polarization coexistence and switching in other kinds of (quasi-)
      three-level optical bistable lasers.

PMID- 30114051
TI  - Simple method for liquid analysis by laser-induced breakdown spectroscopy (LIBS).
AB  - As a fast-developing technique for in situ multi-element analysis method, laser
      induced breakdown spectroscopy - LIBS is, however, developing slowly on liquid
      analysis due to some technical difficulties. We propose a new method, namely
      capillary mode, to quantify the concentrations of the elements in solution using
      LIBS. A Nd:YAG laser with repetition of 10 Hz were used to analyze the solution
      of Na2CrO4 and no any sample preparation in measurements. The experimental
      results show that the splashing of liquid induced by laser pulses is decreased
      significantly and the pollution of mirrors is avoided effectively using liquid
      capillary mode. The results of quantitative analysis for liquid are also improved
      than other method. The calibration curves of Cr and Na are well characterized by
      straight lines and the regression coefficient values of the linear fit are better
      than 0.998. The limits of detection (LODs) of Cr and Na are determined to be 28.9
      mg/L and 1.0 mg/L in this work, respectively. The experimental results show that
      the liquid capillary mode provides a more practical and very simple approach to
      improve accuracy of quantitative element analysis in liquids by LIBS technique.

PMID- 30114052
TI  - Feature issue introduction: light, energy and the environment, 2017.
AB  - The editors introduce the feature issue on "Energy, Light and the Environment
      (LEE) 2017", which is based on the topics presented at a congress of the same
      name held in Boulder, CO, US, from November 6 to November 9. This feature issue
      presents 13 papers selected from the voluntary submissions by attendees who
      presented at the progress and have extended their work into complete research
      articles. The feature issue highlights contributions from authors who presented
      their research at this congress.

PMID- 30114053
TI  - Flexible InGaN nanowire membranes for enhanced solar water splitting.
AB  - III-Nitride nanowires (NWs) have recently emerged as potential photoelectrodes
      for efficient solar hydrogen generation. While InGaN NWs epitaxy over silicon is
      required for high crystalline quality and economic production, it leads to the
      formation of the notorious silicon nitride insulating interface as well as low
      electrical conductivity which both impede excess charge carrier dynamics and
      overall device performance. We tackle this issue by developing, for the first
      time, a substrate-free InGaN NWs membrane photoanodes, through liftoff and
      transfer techniques, where excess charge carriers are efficiently extracted from
      the InGaN NWs through a proper ohmic contact formed with a high electrical
      conductivity metal stack membrane. As a result, compared to conventional InGaN
      NWs on silicon, the fabricated free-standing flexible membranes showed a 10-fold
      increase in the generated photocurrent as well as a 0.8 V cathodic shift in the
      onset potential. Through electrochemical impedance spectroscopy, accompanied with
      TEM-based analysis, we further demonstrated the detailed enhancement within
      excess charge carrier dynamics of the photoanode membranes. This novel
      configuration in photoelectrodes demonstrates a novel pathway for enhancing the
      performance of III-nitrides photoelectrodes to accelerate their commercialization
      for solar water splitting.

PMID- 30114054
TI  - Fast, deterministic computation of irradiance values using a single extended
      source in 3D.
AB  - Presented is a quasi-analytic method for irradiance evaluation through a single
      refractive surface from a single Lambertian source. The method is compared to
      Monte-Carlo raytracing for a sample system, producing in much less time an
      irradiance distribution equal to within the latter's statistical noise. In
      addition to its interest to optical analysis, the method is also useful for
      optical design problems by allowing for fast, noise-free evaluation of merit
      functions, along with their derivatives.

PMID- 30114055
TI  - Electric-field driven photoluminescence probe of photoelectric conversion in
      InGaN-based photovoltaics.
AB  - The spatial distribution of electric field in photovoltaic multiple quantum wells
      (MQWs) is extremely important to dictate the mutual competition of photoelectric
      conversion and optical transition. Here, electric-field-driven photoluminescence
      (PL) in both steady-state and transient-state has been utilized to directly
      investigate the internal photoelectric conversion processes in InGaN-based MQW
      photovoltaic cell. As applying the reversed external electric field, the
      compensation of the quantum confined stark effect (QCSE) in InGaN QW is
      beneficial to help the photoabsorbed minor carriers drift out from the localized
      states, whereas extremely weakening the PL radiative recombination. A directly
      driven force by the reversed external electric field decreases the transit time
      of photocarriers drifting in InGaN QW. And hence, the overall dynamic PL decay
      including both the slow and fast processes gradually speeds up from 19.2 ns at
      the open-circuit condition to 3.9 ns at a negative bias of -3 V. In particular,
      the slow PL decay lifetime declines more quickly than that of the fast one. It is
      the delocalization of photocarriers by electric-field drift that helps to further
      enhance the high-efficiency photoelectric conversion except for the tunneling
      transport in InGaN-based MQW photovoltaics. Therefore, it can be concluded that
      the electric-field PL probe may provide a direct method for evaluating the
      photoelectric conversion in multilayer quantum structures and related
      multijunction photovoltaic cells.

PMID- 30114056
TI  - Variation in efficiency with change in band gap and thickness in thin film
      amorphous silicon tandem heterojunction solar cells with AFORS-HET.
AB  - Numerical simulation of both single and double absorbing layers in amorphous
      silicon thin film solar cell is performed with the use of AFORS-HET. A single
      absorbing layer solar cell with both a-SiH and a-SiGeH is designed and compared
      with a tandem heterojunction solar cell, a-SiC/a-SiH/a-Si(i)/a-SiGeH. Design
      parameters are investigated, compared and optimized. The maximum efficiency for
      each single absorbing layer and for a tandem heterojunction thin film solar cell,
      a-SiC/a-SiH/a-Si(i)/a-SiGeH, is predicted. The results are validated by comparing
      with two different method of analysis.

PMID- 30114058
TI  - Homo-tandem structures to achieve the ideal external quantum efficiency in small
      molecular organic solar cells.
AB  - In this study, we report a homo-tandem structure of small molecular organic solar
      cells (SMOSCs) using identical single-junction devices as sub-cells. The trade
      off between the absorption and internal quantum efficiency (IQE) of single
      junction devices tends to limit the external quantum efficiency (EQE). However,
      multiple-stacked thin cells with maximized IQE in homo-tandem structures amplify
      the absorption to achieve the ideal EQE. As a result, a high power conversion
      efficiency of 7.81% is achieved in tetraphenyldibenzoperiflanthene (DBP):C70
      based homo-tandem SMOSCs, which is 21.8% higher than that in a single-junction
      device.

PMID- 30114057
TI  - Underway spectrophotometry in the Fram Strait (European Arctic Ocean): a highly
      resolved chlorophyll a data source for complementing satellite ocean color.
AB  - Satellite remote sensing of chlorophyll a concentration (Chl-a) in the Arctic
      Ocean is spatially and temporally limited and needs to be supplemented and
      validated with substantial volumes of in situ observations. Here, we evaluated
      the capability of obtaining highly resolved in situ surface Chl-a using underway
      spectrophotometry operated during two summer cruises in 2015 and 2016 in the Fram
      Strait. Results showed that Chl-a measured using high pressure liquid
      chromatography (HPLC) was well related (R2 = 0.90) to the collocated particulate
      absorption line height at 676 nm obtained from the underway spectrophotometry
      system. This enabled continuous surface Chl-a estimation along the cruise tracks.
      When used to validate Chl-a operational products as well as to assess the Chl-a
      algorithms of the aqua moderate resolution imaging spectroradiometer (MODIS-A)
      and Sentinel-3 Ocean Land Color Imager (OLCI) Level 2 Chl-a operational products,
      and from OLCI Level 2 products processed with Polymer atmospheric correction
      algorithm (version 4.1), the underway spectrophotometry based Chl-a data sets
      proved to be a much more sufficient data source by generating over one order of
      magnitude more match-ups than those obtained from discrete water samples.
      Overall, the band ratio (OCI, OC4) Chl-a operational products from MODIS-A and
      OLCI as well as OLCI C2RCC products showed acceptable results. The OLCI Polymer
      standard output provided the most reliable Chl-a estimates, and nearly as good
      results were obtained from the OCI algorithm with Polymer atmospheric correction
      method. This work confirms the great advantage of the underway spectrophotometry
      in enlarging in situ Chl-a data sets for the Fram Strait and improving satellite
      Chl-a validation and Chl-a algorithm assessment over discrete water sample
      analysis in the laboratory.

PMID- 30114059
TI  - Efficient images storage via modulating the atomic spin coherence in a N-type
      system.
AB  - A four-level N-type cold atomic system is proposed for optimizing images storage
      based on the electromagnetically induced transparency (EIT). Both analytical
      analysis and numerical simulation clearly show that the application, during the
      storage time, of an additional intensity-modulated signal field and an additional
      microwave field can impose an intensity and a phase-dependent factors on the
      atomic spin coherence in a controlled manner, then the amplitude of the retrieved
      images can be increased or decreased with an enhancement in the visibility. Our
      results are very promising for the realization of all-optical information
      processing of images coherently stored in EIT media in the future.

PMID- 30114060
TI  - Conductivity mapping of graphene on polymeric films by terahertz time-domain
      spectroscopy.
AB  - Fast inline characterization of the electrical properties of graphene on
      polymeric substrates is an essential requirement for quality control in
      industrial graphene production. Here we show that it is possible to measure the
      sheet conductivity of graphene on polymer films by terahertz time-domain
      spectroscopy (THz-TDS) when all internally reflected echoes in the substrate are
      taken into consideration. The conductivity measured by THz-TDS is comparable to
      values obtained from four point probe measurements. THz-TDS maps of 25x30 cm2
      area graphene films were recorded and the DC conductivity and carrier scattering
      time were extracted from the measurements. Additionally, the THz-TDS conductivity
      maps highlight tears and holes in the graphene film, which are not easily visible
      by optical inspection.

PMID- 30114061
TI  - Optical magnetization, part III: theory of molecular magneto-electric
      rectification.
AB  - A fully quantized analysis is presented of induced magneto-electric rectification
      in individual diatomic molecules in the steady-state regime. Good agreement is
      obtained between this quantum theory and a classical model that includes the same
      key kinematic elements but predicts temporal dynamics as well. At the molecular
      level, an enhanced magneto-electric optical interaction driven by dual optical
      fields E and H* is shown to give rise to a static electric dipole (ED) moment
      oriented along the propagation direction of linearly-polarized light in
      dielectric materials. This longitudinal Hall effect or "charge separation"
      interaction is quadratic with respect to the incident field strength and exhibits
      an induced moment that is limited by the ED transition moment of the molecular
      resonance. Overall, the two-photon dynamics can be described as first
      establishing an electric polarization and imparting orbital angular momentum on
      which the magnetic field exerts torque in the excited state of the molecule.
      Magnetic torque mediates an exchange of orbital and rotational angular momenta
      that de-excites the molecule and simultaneously enhances magneto-electric
      rectification. Material properties that affect magneto-electric response at the
      molecular level are identified.

PMID- 30114062
TI  - Circular-polarization-sensitive absorption in refractory metamaterials composed
      of molybdenum zigzag arrays.
AB  - Circularly polarized light (CPL) is utilized in various fields, including optical
      communication and biological imaging. To overcome the lack of circular
      polarization-sensitive absorbers working at high temperature, a refractory and
      circular-polarization-sensitive absorber comprised of molybdenum zigzag arrays is
      proposed. At certain resonant wavelengths, one component of circular polarization
      is absorbed by confining electromagnetic field in the dielectric layer, while the
      other component is backscattered. The circular-polarization-sensitive absorber
      could be applied as a CPL thermal radiator as well as a reflective linear-to
      circular polarizer. As a CPL thermal radiator, left-handed circular radiation and
      right-handed circular radiation are dominant at different temperatures,
      respectively. As a linear-to-circular polarizer, both perfect left-handed
      circularly polarized light and nearly perfect right-handed circularly polarized
      light are obtained.

PMID- 30114063
TI  - ICF target DT-layer refractive index and thickness from iterative analysis.
AB  - An iterative algorithm based on optical path difference (OPD) and ray deflection
      is proposed to obtain the DT (deuterium-tritium)-layer refractive index and
      thickness of the ICF (inertial confinement fusion) target simultaneously.
      Starting from an assumed initial value, the refractive index and thickness are
      solved back and forth until the iteration stopping criterion is reached.
      Simulations show that the relative retrieval error of the DT-layer refractive
      index is better than 0.05% after finite iterations, and that of the thickness is
      better than 0.1%. Experiments show that the target shell refractive index and
      thickness can be retrieved with a relative error below +/-2%. The test
      uncertainties from experiments were also analyzed.

PMID- 30114064
TI  - Improving the polarization-holography performance of PQ/PMMA photopolymer by
      doping with THMFA.
AB  - Increasing photosensitizer concentration has been considered as an effective
      approach to improve the performance of holographic material. In this paper, we
      report on new method for increasing the saturated dissolvability of
      photosensitizer PQ within polymeric media by introducing copolymerization monomer
      into the PQ/PMMA. The photosensitizer concentration of PQ was increased from
      0.7wt% to 1.3wt%, compared with the typical PQ/PMMA sample. Besides, we
      investigated performance of polarization holographic recordings in typical
      PQ/PMMA and copolymerization monomer-containing PQ/PMMA with the orthogonally
      polarized signal and reference waves. And the doping of THFMA component resulted
      in a significant improvement of diffraction intensity and photosensitivity. In
      addition, high-quality holographic image reconstruction was realized in our home
      made material.

PMID- 30114065
TI  - Coexistence of rectangular and Gaussian-shape noise-like pulses in a figure-eight
      fiber laser.
AB  - We experimentally report the coexistence of the rectangular noise-like pulse
      (NLP) and the Gaussian-shape NLP in a figure-eight fiber laser. Benefiting from
      the strengthened nonlinear effect of a segment of highly nonlinear fiber (HNLF)
      in the cavity, the coexistent NLPs with various patterns, i.e. one rectangular
      pulse with one Gaussian-shape pulse, one rectangular pulse with two Gaussian
      shape pulses and two rectangular pulses with one Gaussian-shape pulse, are formed
      depending on the cavity parameters setting. In particular, the evolution of these
      coexistent NLPs properties with pump power is investigated. It is found that the
      duration of the rectangular pulse always increases, while the Gaussian-shape
      pulse has almost no changes with the increasing pump power. The achieved results
      demonstrated for the first time, to the best of our knowledge, the pulses with
      different shapes can coexist under the NLP regime, which contributes to further
      understanding the fundamental characteristics of the NLPs and multiple pulses.

PMID- 30114066
TI  - Analysis of continuous wave diode pumped cesium laser with gas circulation:
      experimental and theoretical studies.
AB  - Analysis of the operation of flowing-gas low power DPALs is crucial for designing
      high power devices. In particular, the comparison between the measured and
      calculated temperature rise in the laser cell makes it possible to estimate the
      contribution of the quenching of the alkali atoms electronic states to the gas
      heating. Here we report on an experimental and theoretical study of continuous
      wave flowing-gas Cs DPAL with He and CH4 buffer gases, flow velocities of 1-4 m/s
      and pump powers of 30-65 W. In the calculations we used a 3D computational fluid
      dynamics model, solving the fluid mechanics and kinetics equations relevant to
      the laser operation. Maximum CW output power of 24 W with a slope efficiency of
      48% was obtained. The experimental and theoretical values of the power and gas
      temperature are in good agreement. The lasing power was not affected by the flow
      velocity at this range of pump power and the gas temperature rise was only
      several degrees. It was found that the best agreement between the measured and
      calculated temperature rise is achieved for quenching cross-section ~0.05 A2.

PMID- 30114067
TI  - Wave dynamics on toroidal surface.
AB  - Wave dynamics on curved surfaces has attracted growing attention due to its close
      resemblance to the warped space time governed by general relativity. It also
      opens up opportunities for designing functional optical devices such as geodesic
      lenses. In this work we study the wave dynamics on the surface of a torus, a
      shape of considerable interest due to its nontrivial topology. Governed by the
      conservation of angular momentum, light propagates on the torus in two different
      types of modes: one is able to twist around and sweep through the whole surface
      of the torus; the other is confined within a certain angular range along the
      torus latitude direction. The confined mode exhibits an interesting self focusing
      or imaging behavior, which, similar to a geometric lens, shows no dependence of
      wavelength and thus suffers no chromatic aberration. By changing the geometric
      parameters of the torus, both the focusing point and the focusing distance can be
      controlled. Our work provides a new approach to manipulation of light propagation
      on a curved surface under the conservation of angular momentum.

PMID- 30114068
TI  - Study on the power scalability of all-fiber superfluorescent source operating
      near 980 nm.
AB  - The high-power all-fiber superfluorescent source operating near 980 nm is studied
      experimentally and numerically. In experiment, an all-fiber superfluorescent
      source operating near 980 nm is fabricated with the distributed side-coupled
      cladding-pumping (DSCCP) Yb-doped fiber (YDF). By optimizing the active fiber and
      angle-cleaving of the output port, a recorded 17.1-W output power and 14.6% slope
      efficiency of 980-nm ASE are obtained. No parasitic laser oscillation is observed
      at the maximum output power. The power scalability of the source is also
      numerically investigated. A simple but effective method is present to numerically
      determine the threshold of parasitic laser oscillation. It is found that the
      output power can be scaled up to 50 W and 100 W with the optical feedback of each
      output port suppressed to 1.2 * 10-6 and 7 * 10-7, respectively. It is also
      revealed that coupling coefficient should be larger than 6 to realize more than
      50% slope efficiency. These results provide significant guidance for
      understanding and designing the high-power superfluorescent Yb-doped source
      (SYFS) operating near 980 nm and other sorts of three-level fiber sources.

PMID- 30114069
TI  - Circular dichroism enhancement in plasmonic nanorod metamaterials.
AB  - Optical activity is a fundamental phenomenon originating from the chiral nature
      of crystals and molecules. While intrinsic chiroptical responses of ordinary
      chiral materials to circularly polarized light are relatively weak, they can be
      enhanced by specially tailored nanostructures. Here, nanorod metamaterials,
      comprising a dense array of vertically aligned gold nanorods, is shown to provide
      a significant enhancement of the circular dichroism response of an embedded
      material. A nanorod composite, acting as an artificial uniaxial crystal, is
      filled with chiral mercury sulfide nanocrystals embedded in a transparent
      polymer. The metamaterial, being inherently achiral, enables optical activity
      enhancement or suppression. Unique properties of inherently achiral structures to
      tailor optical activities pave a way for flexible characterization of optical
      activity of molecules and nanocrystal-based compounds.

PMID- 30114070
TI  - Witnessing quantum entanglement in ensembles of nitrogen-vacancy centers coupled
      to a superconducting resonator.
AB  - A hybrid quantum device consisting of three ensembles of nitrogen-vacancy centers
      (NVEs) whose spins are collectively coupled to a superconducting coplanar
      waveguide resonator is shown to enable the generation of controllable tripartite
      macroscopic entangled states. The density matrix of such NVEs can be encoded to
      recast a three-qubit system state, which can be characterized in terms of the
      entanglement witnesses in relation to the Greenberger-Horne-Zeilinger (GHZ)
      states. We identify the parameter space within which the generated entangled
      states can have an arbitrarily large overlap with GHZ states, indicating an
      enhanced entanglement in the system.

PMID- 30114071
TI  - Mismatches analysis based on channel response and an amplitude correction method
      for time interleaved photonic analog-to-digital converters.
AB  - A channel mismatch model for time-interleaved photonic analog-to-digital
      converters is built by decomposing both optical time division multiplexing
      channels and the wavelength division multiplexing channels into time channels
      with uniform and equal-amplitude sampling clock. Based on the model, the
      influence of power and timing mismatch of optical sampling pulse trains, optical
      sampling pulse temporal shape mismatches, photodetection bandwidth mismatches on
      the sampling results are analyzed theoretically. Depending on the found
      relationship between unmodulated components and modulated components, an
      effective online amplitude mismatch correction method applicable to wideband
      signals is proposed. The theoretical results are verified on a 4-channel TIPADC
      system. The proposed amplitude mismatch correction method can suppress the spurs
      caused by unmodulated components mismatch and modulated components mismatch by
      ~50 dB and ~30 dB for a two-tone signal, respectively.

PMID- 30114072
TI  - Ray-optical transformation optics with ideal thin lenses makes omnidirectional
      lenses.
AB  - We present the theory of ray-optical transformation optics (RTO) with ideal thin
      lenses and show that ideal-thin-lens RTO devices are omnidirectional lenses. Key
      to designing such devices are two theorems, the loop-imaging theorem, and the
      edge-imaging theorem, which ensure that the interior physical space is distorted
      in the same way for all viewing directions. We discuss the possibility of
      realising such devices using lens holograms or Fresnel lenses, as both are in
      principle capable of changing the directions of rays incident from a specific
      point precisely like an ideal thin lens, thereby enabling macroscopic and broad
      band RTO devices that work for at least one viewing position. Even when
      restricted in this way, our work opens up new possibilities in ray optics. Our
      devices have the potential to form the basis of new microscope objectives,
      virtual-reality headsets, and medical spectacles.

PMID- 30114073
TI  - Bridged-bowtie and cross bridged-bowtie nanohole arrays as SERS substrates with
      hotspot tunability and multi-wavelength SERS response.
AB  - In this paper, we present bridged-bowtie nanohole arrays and cross bridged-bowtie
      nanohole arrays in a gold thin film as surface enhanced Raman scattering (SERS)
      substrates. These SERS substrates not only exhibit large electromagnetic
      enhancement of SERS but also have the SERS enhancement spread over a much larger
      area than what could be present in SERS substrates consisting of nanopillar
      arrays or nanopillar plasmonic nanoantennas. Numerical simulations based on the
      finite difference time domain (FDTD) method are employed to determine electric
      field enhancement factors (EFs) and therefore the electromagnetic SERS
      enhancement factor for these SERS substrates. It was observed that bridged-bowtie
      nanohole arrays and cross bridge-bowtie nanohole arrays exhibit a highest
      electromagnetic SERS enhancement factor (EF) of ~109, which is orders of
      magnitude higher than what has been previously reported for nanohole arrays as
      SERS substrates. This electromagnetic SERS EF (of ~109) is spread over a hotspot
      region of ~100 nm2 (in each periodic unit of the array), which is larger than the
      case of nanopillar arrays. In addition, it was observed that an electromagnetic
      SERS enhancement factor of at least 108 is spread over a large area (500 nm2 in
      each periodic unit of the array), thus increasing the average enhancement factor.
      It was observed that the bridged-bowtie nanohole arrays and the cross bridged
      bowtie nanohole arrays can be employed as effective SERS substrates in both the
      transmission mode and the reflection mode. The resonance wavelength of these
      arrays of nanoholes can be tuned by altering the size of the nanoholes. The
      effects of varying the gold film thickness and the diameter of the bridged-bowtie
      nanoholes forming the arrays were also analyzed. The bridged-bowtie nanohole
      arrays and cross bridged-bowtie nanohole arrays exhibit very high electric field
      enhancement factors (EFs) at more than one wavelength, and can therefore be used
      to obtain a multi-wavelength SERS response. Moreover, the cross bridged-bowtie
      nanohole array allows the tunability of the position of the hotspot with the
      rotation of the direction of the polarization of incident field.

PMID- 30114074
TI  - 50 Gb/s short-reach interconnects with DSP-free direct-detection enabled by CAPS
      codes.
AB  - We experimentally demonstrate 50 Gb/s transmission below an uncorrected bit error
      rate (BER) of 10-3 in the C band over a transmission reach that extends from 0 to
      20 km using combined amplitude and phase shift (CAPS) codes. The CAPS signal,
      which is not required to be specifically dispersion compensated for each reach
      within the 20 km operating range, is amenable for simple direct detection using a
      single photodetector without any subsequent digital signal processing (DSP).
      Hence, the presented solution constitutes a potentially attractive low cost
      solution for mobile Xhaul applications employing single mode fiber interconnects
      with reaches extending to 20 km. Furthermore, the CAPS signaling is compared to
      other modulation schemes all delivering 50 Gb/s and is found to outperform on-off
      keying (OOK), 4-level pulse amplitude modulation (PAM4) and dispersion
      precompensated OOK in terms of dispersion tolerance. At a lower reach of 10 km,
      the maximum bit rate that can be achieved using CAPS coding at a BER below 10-3
      is found to increase to 67 Gb/s. In addition, using the same testbed, we
      experimentally tested the IQ duobinary modulation format, which is an alternative
      format that approximates the CAPS transmitted waveforms in order to omit the need
      for a power consuming digital-to-analog converter (DAC) to generate the
      transmitted waveforms at the expense of slightly worse dispersion tolerance.
      Though the IQ duobinary format can be in principle generated using a simple DAC
      less analog transmitter, our proof-of-concept experiment used a DAC to emulate
      the analog transmitter by generating the corresponding transmitted waveforms due
      to unavailability of all required analog parts. The IQ duobinary format was found
      experimentally to enable 50 Gb/s over a reach of ~17 km; that is slightly less
      than a CAPS signal at the same bit rate. Finally, we verified the excellent
      performance of the CAPS signaling in an ASE-limited regime where the CAPS signal
      achieved very low OSNR penalty after 10 km relative to OOK in back-to-back.

PMID- 30114075
TI  - Experimental investigation of broad area quantum cascade lasers under external
      feedback.
AB  - Mode creation and temporal response of broad-area quantum cascade lasers (BA-QCL)
      placed within an external feedback cavity are described in this publication. The
      critical feedback parameter becomes the mirror angle relative to the BA-QCL
      facet. With judicious angle choices, a plethora of curious modes can be created,
      each with their particular threshold and slope efficiency. These range from a
      nearly single far-field intensity peak to highly multimode emission similar to
      their diode counterparts. Dynamics are strongly dominated by transverse mode
      competition ranging for less than 20MHz to greater than 100MHz. When the mirror
      is parallel to the facet, higher frequency external cavity oscillations become
      undamped.

PMID- 30114076
TI  - Single-shot time-gated fluorescence lifetime imaging using three-frame images.
AB  - Qualitative and quantitative measurements of complex flows demand for fast single
      shot fluorescence lifetime imaging (FLI) technology with high precision. A
      method, single-shot time-gated fluorescence lifetime imaging using three-frame
      images (TFI-TGFLI), is presented. To our knowledge, it is the first work to
      combine a three-gate rapid lifetime determination (RLD) scheme and a four-channel
      framing camera to achieve this goal. Different from previously proposed two-gate
      RLD schemes, TFI-TGFLI can provide a wider lifetime range 0.6 ~ 13ns with
      reasonable precision. The performances of the proposed approach have been
      examined by both Monte-Carlo simulations and toluene seeded gas mixing jet
      diagnosis experiments. The measured average lifetimes of the whole excited areas
      agree well with the results obtained by the streak camera, and they are 7.6ns (N2
      = 7L/min; O2 < 0.1L/min) and 2.6ns (N2 = 19L/min; O2 = 1L/min) with the standard
      deviations of 1.7ns and 0.8ns among the lifetime image pixels, respectively. The
      concentration distributions of the quenchers and fluorescent species were further
      analyzed, and they are consistent with the experimental settings.

PMID- 30114077
TI  - Dynamic beam control via Mie-resonance based phase-change metasurface: a
      theoretical investigation.
AB  - Here, a non-volatile optically controllable metasurface is theoretically
      investigated at the operating wavelength of 1.55 MUm by utilizing low loss phase
      change Ge2Sb2Se4Te1 (GSST) as the constituent material of high-index resonant
      element. The GSST nanobar as the proposed building block supports both the
      magnetic and electric resonances whose strength and spectral positions can be
      governed by varying the GSST crystallization level. The possibility of operating
      at off-resonance regime (middle of geometrical resonances) and preventing from
      the concurrence of high field confinement and large dissipative loss provide the
      opportunity to obtain high reflection level (varying between 0.6 and 0.8) and
      wide phase agility (~270 degrees ). The phase distribution at the interface of an
      array of GSST nanobars can be tailored by selective modification of the
      crystallization level of nanobars leading to active control over the wave-front
      of reflected beam with numerically calculated reflection efficiency higher than
      45%.

PMID- 30114078
TI  - High resolution continuous wave terahertz spectroscopy on solid-state samples
      with coherent detection.
AB  - We systematically investigate the data analysis methods in terahertz frequency
      domain spectroscopy (THz-FDS) with coherent detection. We demonstrate that the
      Hilbert transform method is one of the most appropriate for data processing in
      THz-FDS. By converting frequency-domain signal into time domain with further data
      processing, the system noise due to Fabry-Perot (FP) interference is greatly
      restrained. Accurate permittivity of lactose monohydrate is successfully
      extracted under the condition of the existence of atmospheric water vapor. Our
      work greatly promotes the development of THz spectroscopy in practical
      applications.

PMID- 30114079
TI  - Establishment of the relationship between the electron energy and the electron
      injection for AlGaN based ultraviolet light-emitting diodes.
AB  - This work establishes the relationship between the electron energy and the
      electron concentration within the multiple quantum wells (MQWs) for AlGaN based
      deep ultraviolet light-emitting diodes (DUV LEDs). The electron energy of
      different values can be obtained by modulating the Si doping concentration in the
      n-AlGaN layer and/or engineering the polarization induced interface charges. The
      modulated Si doping concentration in the n-AlGaN layer will cause the interface
      depletion region within which the electric field can be generated and then tunes
      the electron energy. The polarization induced charges and the polarization
      induced electric field can be obtained by stepwisely reducing the AlN composition
      for the n-AlGaN layer along the [0001] orientation. We find that the electron
      concentration in the MQWs can be increased once the electron energy is reduced to
      a proper level, which correspondingly improves the external quantum efficiency
      (EQE) for DUV LEDs. According to our investigations, it is more advisable to
      adopt the n-AlGaN layer with the stepwise AlN composition, which can make both
      the EQE and the wall plug efficiency high.

PMID- 30114080
TI  - Unusual eigenmodes of wire-medium endoscopes: impact on transmission properties.
AB  - Wire-medium endoscopes represent a promising tool of THz sensing/imaging. Bending
      should not critically harm the endoscope operation and the issue of bending
      losses is that of key importance for any endoscope. In this paper we show that
      the frequency-averaged power transmittance of a wire-medium endoscope is weakly
      sensitive to the bending. However, the frequency dispersion of the power
      loss/transmittance of the endoscope is strongly oscillating. Frequency maxima of
      the loss factor result from unusual eigenmodes of an elongated wire medium
      sample. These modes comprise power vortices and their sensitivity to the sample
      bending seems to be a critical issue for the future of wire-medium endoscopes.

PMID- 30114081
TI  - Effects of combined process of reactive ion etching and dynamic chemical etching
      on UV laser damage resistance and surface quality of fused silica optics.
AB  - We investigate the interest of combined process of reactive ion etching (RIE) and
      dynamic chemical etching (DCE) as a final step after polishing to improve the
      laser damage resistance of fused silica optics at the wavelength of 355 nm. The
      investigation is carried out on the polished fused silica optics by changing the
      RIE depth while keeping the DCE depth fixed. We evidence that the combined
      etching process can effectively remove the damage precursors on the fused silica
      surface and thus improve its laser-induced damage threshold exceeding the level
      of the deep HF-etched surface. The effects of the combined etching depth on the
      surface roughness and surface error are also studied systematically. We show that
      the combined shallow etching can achieve better overall surface quality. Deeper
      etching will cause surface quality degradation of the fused silica optics, which
      is believed to be associated with the chemical etching during the combined
      process. Given that HF acid processing will degrade the surface quality of fused
      silica optics, the combined shallow etching appears as a pertinent alternative to
      HF-based deep etching.

PMID- 30114082
TI  - Passive coherent beam combination of three Nd:YAG lasers using cascaded Michelson
      type compound cavities.
AB  - A coaxial multibeam passive coherent combination of lasers with improved beam
      quality is proposed and verified using cascaded Michelson-type cavities, in which
      4f optical systems are used to compensate for the beam waist separation between
      the combined adjacent lasers. A proof-of-concept experiment shows that three 65 W
      Nd:YAG lasers with an M2 factor of about 5.5 were coherently combined into a
      124.4 W single-lobed output improving the M2 factor to 1.36. The central lobe
      accounted for 76% of the total power, corresponding to a total combined
      efficiency of 66.7%.

PMID- 30114083
TI  - Cross-Kerr effect in a parity-time symmetric optomechanical system.
AB  - The cross-Kerr effects between the cavity and the mechanical oscillator in a
      parity-time symmetric optomechanical system are investigated. It is found that in
      the double-passive case there appears an asymmetric optomechanically induced
      transparency (OMIT) spectrum which is composed of a broad absorption peak located
      around the resonant point and a absorption line at the frequency position mainly
      determined by the Kerr interaction. The distinctive asymmetry induced by the
      cross-Kerr coupling is precisely demonstrated by the analytic findings. In the
      passive-active case, the resonance peaks in the OMIT spectrum are increased with
      the weak tunnel coupling, which is contrary to that in the double-passive case.
      When the tunnel coupling is increased up in the strong coupling region, the broad
      absorption peak and the absorption line in the OMIT spectrum are sequentially
      changed into the amplification ones, and the central amplification dip is split
      into two parts due to the normal mode splitting induced by the strong tunnel
      coupling. This can be used to realize a switching from absorption to
      amplification by only adjusting the tunnel interaction.

PMID- 30114084
TI  - Reevaluation of radiation reaction and consequences for light-matter interactions
      at the nanoscale.
AB  - In the context of electromagnetism and nonlinear optical interactions, damping is
      generally introduced as a phenomenological, viscous term that dissipates energy,
      proportional to the temporal derivative of the polarization. Here, we follow the
      radiation reaction method presented in [Phys. Lett. A157, 217 (1991)], which
      applies to non-relativistic electrons of finite size, to introduce an explicit
      reaction force in the Newtonian equation of motion, and derive a hydrodynamic
      equation that offers new insight on the influence of damping in generic plasmas,
      metal-based and/or dielectric structures. In these settings, we find new damping
      dependent linear and nonlinear source terms that suggest the damping coefficient
      is proportional to the local charge density and nonlocal contributions that stem
      from the spatial derivative of the magnetic field. We discuss the conditions that
      could modify both linear and nonlinear electromagnetic responses.

PMID- 30114085
TI  - Design, analysis of self-configurable modular adjustable latch lock for segmented
      space mirrors.
AB  - This paper presents a connection mechanism for autonomous self-assembly of
      segmented space mirrors. Using this connection mechanism, space mirrors can be
      autonomously captured, positioned, locked and adjusted. The purpose of assembling
      space mirrors on orbit is to overcome the limits of launch volume and mass and
      provide a feasibility for future extremely large space telescope in order to
      improve optical performance to function as monolithic mirrors. In this paper,
      first, the design details and operation principle of the connection mechanism are
      presented. Then, based on the initial capture conditions, a double-contact model
      is investigated. And simulated results of the dynamic and optical performance
      show that the proposed mechanism overcomes significant alignment errors and is
      considered suitable for space optical system.

PMID- 30114086
TI  - Accurate photonic waveguide characterization using an arrayed waveguide
      structure.
AB  - Measurement uncertainties in the techniques used to characterize loss in photonic
      waveguides becomes a significant issue as waveguide loss is reduced through
      improved fabrication technology. Typical loss measurement techniques involve
      environmentally unknown parameters such as facet reflectivity or varying coupling
      efficiencies, which directly contribute to the uncertainty of the measurement. We
      present a loss measurement technique, which takes advantage of the differential
      loss between multiple paths in an arrayed waveguide structure, in which we are
      able to gather statistics on propagation loss from several waveguides in a single
      measurement. This arrayed waveguide structure is characterized using a swept
      wavelength interferometer, enabling the analysis of the arrayed waveguide
      transmission as a function of group delay between waveguides. Loss extraction is
      only dependent on the differential path length between arrayed waveguides and is
      therefore extracted independently from on and off-chip coupling efficiencies,
      which proves to be an accurate and reliable method of loss characterization. This
      method is applied to characterize the loss of the silicon photonic platform at
      Sandia Labs with an uncertainty of less than 0.06 dB/cm.

PMID- 30114087
TI  - Energy transfer enhanced near-infrared spectral performance in bismuth/erbium
      codoped aluminosilicate fibers for broadband application.
AB  - The energy transfer processes between bismuth active centers (BACs) and Er3+ in
      Bi/Er codoped fiber (BEDF) are investigated and, with clear experimental
      evidence, observed for the first time. Under 980 nm pumping, we observed an
      energy transfer from Er3+ to BAC-Al in BEDF, evidenced by the enhanced NIR
      emission and lifetime when compared with a bismuth doped fiber (BDF). Under 830
      nm pumping, the spectral performance of Er3+ in BEDF is found to benefit from BAC
      Al->Er3+, evidenced by the notable increase in NIR emission, lifetime, and gain.
      The observations confirm that proper codoping of Er in Bi-doped fibers could
      introduce significant changes to emission through ET processes and provides a
      promising strategy for improving spectral performance over the 1000-1600 nm
      range.

PMID- 30114088
TI  - Strehl ratio for optical systems with ultrafast illumination.
AB  - We study ultrafast laser pulse properties as they propagate through optical
      systems. A modified definition of Strehl ratio is used to quantify the chromatic
      and temporal behavior of ultrafast laser pulses at the optical focus. We propose
      this parameter as a figure of merit for the design and analysis of optical
      systems with ultrafast illumination. A simple method to obtain approximate
      numerical solutions is given with the help of ray tracing software. Effects of
      monochromatic aberrations and material dispersion up to the second order are
      discussed.

PMID- 30114089
TI  - Polymer optical fiber Bragg grating inscription with a single Nd:YAG laser pulse.
AB  - We experimentally demonstrate the first polymer optical fiber Bragg gratings
      inscribed with only one Nd:YAG laser (266 nm) pulse. The gratings have been
      inscribed in a single-mode poly (methyl methacrylate) optical fiber, with a core
      doped with benzyl dimethyl ketal for photosensitivity enhancement. One laser
      pulse with a duration of 8 ns and energy of 72 uJ is adequate to introduce a
      refractive index change of 0.5 * 10-4 in the fiber core. The stability of the
      gratings has been confirmed and the strain and temperature sensitivity
      measurements demonstrate their tunable properties.

PMID- 30114090
TI  - Burst-mode OH/CH2O planar laser-induced fluorescence imaging of the heat release
      zone in an unsteady flame.
AB  - The paper presents simultaneous high-speed (7.5 kHz) planar laser-induced
      fluorescence (PLIF) of formaldehyde (CH2O) and the hydroxyl-radical (OH) for
      visualization of the flame structure and heat release zone in a non-premixed
      unsteady CH4/O2/N2 flame. For this purpose, a dye laser designed for high-speed
      operation is pumped by the second-harmonic 532 nm output of a Nd:YAG burst-mode
      laser to produce a tunable, 566 nm beam. After frequency doubling a high-energy
      kHz-rate narrowband pulse train of approximately 2.2 mJ/pulse at 283 nm is used
      for excitation of the OH radical. Simultaneously, CH2O is excited by the
      frequency-tripled output of the same Nd:YAG laser, providing a high-frequency
      pulse train over 10 ms in duration at high pulse energies (>100 mJ/pulse). The
      excitation energies enable signal-to-noise ratios (SNRs) of ~10 and ~60 for CH2O
      and OH PLIF, respectively, using a single high-speed intensified CMOS camera
      equipped with an image doubler. This allows sufficient SNR for investigation of
      the temporal evolution of the primary heat release zone and the local flame
      structure at kHz rates from the spatial overlap of the OH- and CH2O-PLIF signals.

PMID- 30114091
TI  - Compressed sensing FTIR nano-spectroscopy and nano-imaging.
AB  - Infrared scattering scanning near-field optical microscopy (IR s-SNOM) provides
      for spectroscopic imaging with nanometer spatial resolution, yet full spatio
      spectral imaging is constrained by long measurement times. Here, we demonstrate
      the application of compressed sensing algorithms to achieve hyperspectral FTIR
      based nano-imaging at an order of magnitude faster imaging speed to achieve the
      same spectral content compared to conventional approaches. At the example of the
      spectroscopy of a single vibrational resonance, we discuss the relationship of
      prior knowledge of sparseness of the employed Fourier base functions and sub
      sampling. Compressed sensing nano-FTIR spectroscopy promises both rapid and
      sensitive chemical nano-imaging which is highly relevant in academic and
      industrial settings for fundamental and applied nano- and bio-materials research.

PMID- 30114092
TI  - High repetition rate, uJ-level, CPA-free ultrashort pulse multipass amplifier
      based on Ho:YLF.
AB  - We report on CPA-free multipass amplification of ps-pulses in Holmium-doped
      yttrium lithium fluoride (Ho:YLF) crystals up to uJ pulse-energy-covering
      repetition rates from 10 kHz up to 500 kHz. The seed pulses at a wavelength of
      2.05 um are provided by a Ho-based all-fiber system consisting of a soliton
      oscillator and a subsequent pre-amplifier followed by a free-space AOM as pulse
      picker. Considering the achieved pulse peak power at MW-level, this system is a
      powerful tool for efficient pumping of parametric conversion stages addressing
      the highly demanded mid-IR spectral region.

PMID- 30114093
TI  - Binary signaling design for visible light communication: a deep learning
      framework.
AB  - This paper develops a deep learning framework for the design of on-off keying
      (OOK) based binary signaling transceiver in dimmable visible light communication
      (VLC) systems. The dimming support for the OOK optical signal is achieved by
      adjusting the number of ones in a binary codeword, which boils down to a
      combinatorial design problem for the codebook of a constant weight code (CWC)
      over signal-dependent noise channels. To tackle this challenge, we employ an
      autoencoder (AE) approach to learn a neural network of the encoder-decoder pair
      that reconstructs the output identical to an input. In addition, optical channel
      layers and binarization techniques are introduced to reflect the physical and
      discrete nature of the OOK-based VLC systems. The VLC transceiver is designed and
      optimized via the end-to-end training procedure for the AE. Numerical results
      verify that the proposed transceiver performs better than baseline CWC schemes.

PMID- 30114094
TI  - Non-linear adaptive three-dimensional imaging with interferenceless coded
      aperture correlation holography (I-COACH).
AB  - Interferenceless coded aperture correlation holography (I-COACH) is an incoherent
      digital holography technique for imaging 3D objects without two-wave
      interference. In I-COACH, the object beam is modulated by a pseudorandom coded
      phase mask (CPM) and propagates to the camera where its intensity pattern is
      recorded. The image of the object is reconstructed by a cross-correlation of the
      object intensity pattern with a point intensity response of the system, whereas
      the light from both the object and the point, are modulated by the same CPM. In
      order to recover the image of the object without bias level and background noise,
      multiple intensity recordings are necessary for both objects as well as the point
      object, which in turn significantly reduces the time resolution of imaging. In
      this study, a non-linear reconstruction technique is developed to reconstruct the
      image of the object with only a single camera shot. Furthermore, the proposed
      technique is adaptive to different experimental conditions in the sense of
      finding different optimal parameters for each experiment. The new method has been
      implemented on a regular I-COACH system in both transmission as well as
      reflection illumination modes.

PMID- 30114095
TI  - Perfect ultraviolet absorption in graphene using the magnetic resonance of an all
      dielectric nanostructure.
AB  - The enhancement of light-matter interaction for monolayer graphene is of great
      importance on many photonic and optoelectronic applications. With the aim of
      perfect ultraviolet trapping on monolayer graphene, we adopt the design of an all
      dielectric nanostructure, in which the magnetic resonance of optical field is
      combined with an ultraviolet mirror. The physics inside is revealed in comparison
      with the conventional plasmonic perfect absorber, and various influence factors
      of absorption bands are systematically investigated. In the ultraviolet range, an
      optimized absorbance ratio up to 99.7% is reached, which is 10 times more than
      that of the suspended graphene, and the absorption bands are linearly
      reconfigurable by angular manipulation of incident light. The scheme for perfect
      ultraviolet trapping in a sub-nanometer scale paves the way for developing more
      promising ultraviolet devices based on graphene and potentially other 2D
      materials.

PMID- 30114096
TI  - Generation of wavelength- and OAM-tunable vortex beam at low threshold.
AB  - Wavelength- and OAM- tunable laser with large tunable range is the key source for
      the application in large capacity optical communications. In this paper, we
      demonstrate a wavelength- and OAM-tunable vortex laser in a 1.2 W single mode
      fiber coupled LD pumped Yb:phosphate laser. A z-type cavity has been used to
      precisely control the laser mode diameter. A thin film polarizer (TFP) is
      inserted to finely control the intra-cavity loss and tune the wavelength.
      Corresponding laser fundamental mode to pump beam ratio has been optimized to
      decrease the pump threshold for high order HG mode running. A pair of cylindrical
      lenses has been used to convert the HG mode to vortex output. The vortex beam
      with OAM-tunable range from 1h to 14 h with wavelength tuning range of ~36.2 nm
      for LG0,1 vortex beam, and ~14.5 nm for LG0,14 vortex beam at pump power of only
      1.2 W have been realized, which is the largest tuning range of both OAM and
      wavelength at ~1 W pump power range to the best of our knowledge.

PMID- 30114097
TI  - Development of a whiteness formula for surface colors under an arbitrary light
      source.
AB  - The whiteness specification is critically important in surface color industry,
      especially when fluorescent whitening agents (FWAs) are added to objects. The CIE
      whiteness formula, the most widely used whiteness formula, only characterizes the
      whiteness under CIE standard D65, which ignores the change of whiteness under
      different light sources due to the spectral content of the light sources. Though
      the adoption of a Chromatic Adaptation Transform (CAT02) in the CIE whiteness
      formula was found effective in recent studies, it failed to allow a comparison
      across different correlated color temperatures (CCTs). In this study, a
      haploscopic viewing condition was employed, with a D65 simulator in the left
      booth, for evaluating the whiteness of eight samples under different light
      sources in the right booth. The whiteness of the four samples under the D65
      simulator was employed as a whiteness scale to aid the evaluation. Based on the
      experiment results, the characterization of whiteness for a surface under an
      arbitrary light source is proposed to use the CIE whiteness formula with the
      sample chromaticities being transformed using CAT02 and an adjusted degree of
      chromatic adaptation factor D.

PMID- 30114098
TI  - Dual-cavity digital laser for intra-cavity mode shaping and polarization control.
AB  - In this paper, we present a digital laser for on-demand modes with polarization
      control based on a single intra-cavity spatial light modulator (SLM). We employ a
      phase-only SLM as the back reflector in a dual-cavity resonator. We prove that we
      can digitally control and switch lasing modes with desired linear polarization at
      video rates. Moreover, we experimentally generate vector beams based on the
      selection and coherent summation of two orthogonally polarized Hermite-Gaussian
      (HG) beams inside the resonator.

PMID- 30114099
TI  - Coexistence of dissipative soliton and stretched pulse in dual-wavelength mode
      locked Tm-doped fiber laser with strong third-order dispersion.
AB  - Mode-locked lasers with strong high order dispersion exhibit rich nonlinear
      dynamics. Here we numerically and experimentally demonstrate coexistence of
      dissipative soliton (DS) and stretched pulse (SP) in a dual-wavelength mode
      locked Tm-doped fiber laser with strong third-order dispersion (TOD), where the
      DS and SP show completely different pulse duration and peak power. Wavelength
      dependent feature of the net cavity group-velocity dispersion (GVD) leaded by the
      strong TOD plays a key role for the coexistence patterns. To our best knowledge,
      this is the first demonstration of the coexistence of different mode-locked pulse
      regimes with strong laser cavity TOD.

PMID- 30114100
TI  - Ring and unimodal angular-frequency distribution of THz emission from two-color
      femtosecond plasma spark.
AB  - We study angular and frequency-angular distributions of the terahertz (THz)
      emission of the low-frequency region (0.3-3 THz) from a two-color femtosecond
      plasma spark experimentally and in three-dimensional numerical simulations. We
      investigate the dependence of the angular shapes of the THz radiation on focusing
      conditions and pulse durations by using two laser facilities (pulse durations 35
      and 150 fs) for different focusing geometries. Our experiments and simulations
      show that decrease in the numerical aperture from NA ~0.2 to NA ~0.02 results
      simultaneously in (I) squeezing of the THz angular distribution and (II)
      formation of the bright conical emission in the THz range. The moderate focusing
      NA ~0.05, which forms the relatively narrow unimodal THz angular distribution, is
      identified as optimal in terms of angular divergence. Numerical simulations with
      carrier wave resolved show that bright THz ring structures appear at the
      frequencies >=2 THz for longer focuses (NA ~0.02), while for optimal focusing
      conditions NA ~0.05 the conical emission develops at THz frequencies higher than
      10 THz.

PMID- 30114101
TI  - Fabry-Perot type polariton modes and their dynamics revealed by Young's
      interference experiment.
AB  - We report experimental studies on the Fabry-Perot (F-P) type polariton modes and
      their dynamics using a modified Young's double-slit interference technique. The
      technique was based on the angle-resolved micro-photoluminescence spectroscopy
      and optimized for nanostructure measurements. Using this technique, we directly
      revealed the parity of the F-P type polariton modes from the angle-dependent
      interference spectra. Moreover, clear features of mode competition were observed
      from the power dependence of the interference patterns. The observed competition
      behaviors can be well simulated by a five-level rate equation model.

PMID- 30114102
TI  - Experimental simulation of ranging action using Si photonic crystal modulator and
      optical antenna.
AB  - Time of flight light detection and ranging (LiDAR) has been tested and used as a
      key device for auto-driving of vehicles. Frequency-modulated continuous-wave
      (FMCW) LiDAR potentially achieves a high sensitivity. In this study, we
      fabricated and tested two components of FMCW LiDAR based on Si photonics. The
      ranging action was also experimentally simulated. A Si photonic crystal slow
      light Mach-Zehnder modulator was driven by linearly frequency-chirped signals to
      generate quasi-frequency-modulated signal light. Then, the light was inserted
      into a fiber delay line of 20-320 m. Its output was irradiated to a photonic
      crystal slow beam steering device that acted as an optical antenna via a free
      space transmission. The detected light was mixed with the reference light
      branched after the modulation in balanced photodiodes. A sufficiently sharp beat
      spectrum was observed, whose frequency well agreed with that expected for the
      delay line. The experimental simulation of the FMCW LiDAR, thus, was achieved.

PMID- 30114103
TI  - Tunable absorption as multi-wavelength at infrared on graphene/hBN/Al grating
      structure.
AB  - This work designs a graphene/hBN/Al grating anisotropic hybrid structure. Formed
      by strong coupling between plasmonic Magnetic polaritons (MPs) in the metal
      grating and phonon-plasmon polaritons, hybrid hyperbolic phonon-plasmon
      polaritons in the graphene/hBN film have been excited, resulting in three sharp,
      high absorption peaks, which are 0.75, 0.97 and 0.97, formed at 5.92 MUm, 6.32
      MUm, and 7.64 MUm respectively. The absorption mechanisms have been theoretically
      analyzed. Local electromagnetic field and power dissipation density are depicted
      for further elucidating the underlying mechanisms. The different structural
      parameters and chemical potential, which affect the absorption peak were
      discussed. These numerical results can provide potential application in the field
      of optical detection and optoelectronic.

PMID- 30114104
TI  - Sparsity-based super-resolution microscopy from correlation information.
AB  - For more than a century, the wavelength of light was considered to be a
      fundamental limit on the spatial resolution of optical imaging. Particularly in
      light microscopy, this limit, known as Abbe's diffraction limit, places a
      fundamental constraint on the ability to image sub-cellular organelles with high
      resolution. However, modern microscopy techniques such as STED, PALM, and STORM,
      manage to recover sub-wavelength information, by relying on fluorescence imaging.
      Specifically, PALM/STORM acquire large sequences of fluorescence images from
      molecules attached to the organelles within the imaged specimen, such that in
      each frame only a small set of fluorophores are active. The position of each
      fluorophore can be found accurately in each frame, and the image is recovered by
      superimposing the points from all frames. The resulting grainy image is
      subsequently smoothed to produce the final super-resolved image with a resolution
      of tens of nano-meters. However, because PALM/STORM rely on many (>10,000)
      exposures, they suffer from poor temporal resolution. To address that, super
      resolution optical fluctuation imaging (SOFI) was shown to produce sub
      diffraction images with increased temporal resolution, by allowing for higher
      fluorophore density and exploiting the temporal statistics of the emissions.
      However, the improved temporal resolution of SOFI comes at the expense of its
      spatial resolution, which is not as high as that of PALM/STORM. Here, we present
      a new method called SPARCOM: sparsity-based super-resolution correlation
      microscopy, which combines a shorter integration time than previously reported
      with spatial resolution comparable to PALM and STORM. SPARCOM relies on sparsity
      in the correlation domain, exploiting the sparse distribution of fluorescent
      molecules and the lack of correlation between different emitters. We demonstrate
      our technique in simulations and in experiments and provide comparisons to state
      of-the-art high density methods.

PMID- 30114105
TI  - Polarization independent fast BOTDA based on pump frequency modulation and cyclic
      coding.
AB  - We propose and experimentally demonstrate a scheme of polarization independent
      fast Brillouin optical time domain analysis (F-BOTDA) based on pump frequency
      modulation and cyclic coding. The Brillouin gain spectrum (BGS) is reconstructed
      by fast scanning frequency of the pump using an arbitrary waveform generator
      (AWG). To realize long range distributed dynamic strain sensing, polarization
      diversity technique and cyclic coding are employed to eliminate polarization
      fading and enhance the signal-to-noise ratio (SNR). Based on this configuration,
      the need of trace averaging is avoided, sensing speed of 440 Hz is achieved over
      ~2 km single mode fiber with 50 scanning frequencies and a spatial resolution of
      1.5 m. Vibration events up to 40 Hz are successfully identified.

PMID- 30114106
TI  - Pulse propagation in the slow and stopped light regime.
AB  - Electromagnetic pulse propagation in the slow light regime and near a zero group
      velocity point is relevant to a plethora of potential applications, and has
      analogies in numerous other wave systems. Unfortunately, the standard frequency
      based formulation for pulse propagation is unsuitable for describing the dynamics
      in such regimes, due to the divergence of the dispersion coefficients. Moreover,
      in the presence of absorption, it is not clear how to interpret the propagation
      dynamics due to the drastic change induced by absorption upon the dispersion
      curves. As a remedy, we present an alternative momentum-based formulation, which
      is rapidly converging in these regimes, and naturally suitable for lossy and
      nonlinear media. It is specialized to a waveguide geometry which provides a
      significant simplification with respect to existing momentum-based schemes. Doing
      so, we provide a somewhat alternative, yet intuitive picture of the seeming
      enhanced absorption and nonlinear response in these regimes, and show that light
      matter interactions are not enhanced in the slow/stopped light regimes.

PMID- 30114107
TI  - Annular beam driven high harmonic generation for high flux coherent XUV and soft
      X-ray radiation.
AB  - Separation of the high average power driving laser beam from the generated XUV to
      soft-X-ray radiation poses great challenges in collinear HHG setups due to the
      losses and the limited power handling capabilities of the typically used
      separating optics. This paper demonstrates the potential of driving HHG with
      annular beams, which allow for a straightforward and power scalable separation
      via a simple pinhole, resulting in a measured driving laser suppression of 5?10
      3. The approach is characterized by an enormous flexibility as it can be applied
      to a broad range of input parameters and generated photon energies. Phase
      matching aspects are analyzed in detail and an HHG conversion efficiency that is
      only 27% lower than using a Gaussian beam under identical conditions is
      demonstrated, revealing the viability of the annular beam approach for high flux
      coherent short-wavelength sources and high average power driving lasers.

PMID- 30114108
TI  - Research on the spectral phase correction method for the atmospheric detection in
      open space.
AB  - During the atmospheric detection process in open space, the excessive phase noise
      is introduced into the signal, due to the atmospheric turbulence, which causes
      the intensity and phase fluctuation. In the previous study, a spectral data
      processing method based on the co-frequency and dual-wave has been used to reduce
      the influence of the scintillation noise from the atmospheric turbulence in open
      space, while the influence of the phase noise remains to be solved. So the
      wavelength modulated signal is theoretically analyzed at first. On studying the
      relationship between the dual-waves in one cycle to eliminate the phase
      fluctuation and reduce the phase fluctuation caused by the atmospheric
      turbulence, a new method of the spectral phase correction for the open space
      atmospheric detection has been proposed. An atmospheric detection experiment on
      the phase correction in the open space based on co-frequency and dual-wave has
      been carried out. The results show that the maximum fluctuation of the spectral
      signal processed with this method is 1.06%, while the power spectral density
      fluctuation is suppressed below 50Hz, and the Allan analysis result is 8.8 * 10
      8(1s). Compared with the traditional concentration inversion method using 2f
      wavelength modulation and the classical light intensity elimination, the proposed
      phase correction method can effectively reduce the fluctuation of random noise
      caused by the short-term atmospheric turbulence and the laser flashing to improve
      the stability of the concentration measurement, which has practical engineering
      value.

PMID- 30114109
TI  - See-through display combined with holographic display and Maxwellian display
      using switchable holographic optical element based on liquid lens.
AB  - We report a switchable holographic optical element based on a liquid lens for a
      see-through display. For the switchable holographic optical element, we recorded
      two optical components in the holographic film in two steps. A numerical
      simulation was also done to define the recording and reconstruction conditions.
      After the recording process, the entire system was changed from 4f optics to
      Maxwellian optics by changing wavefront of the reference wave using a liquid
      lens. The diffraction efficiency was 0.46 for a single element recording and
      around 0.14 for a double element recording. The holographic display and the
      Maxwellian display were successfully switched without any crosstalk. The field of
      view and eye box of the holographic display were 1 degrees  and 4.36 mm,
      respectively, and the field of view and the eye box of the Maxwellian display
      were 3.8 degrees  and 23.2 um, respectively. In the proposed system, spatial
      frequency filtering by the liquid lens and image shape distortion seriously
      affected the hologram image. However, we successfully verified the feasibility of
      our proposed switchable holographic optical element using a liquid lens.

PMID- 30114110
TI  - Design and analysis of a five-mirror derotator with minimal instrumental
      polarization in astronomical telescopes.
AB  - It is well known that derotator is commonly used to compensate for image rotation
      in astronomical telescopes. The classical derotator, consisting of three mirrors,
      is named K-mirror. The main disadvantage of the K-mirror is that it has high
      instrumental polarization, causing a larger polarization measurement error in
      polarimetry. In the paper, we proposed a new design of the derotator based on the
      Mueller matrix transformation theory of mirrors in polarized light. The new
      designed derotator contains five mirrors and is called five-mirror derotator. It
      has a very small instrumental polarization, overcoming the shortcomings of the
      classical K-mirror. A novel method is applied to compensate for the beam shift
      induced by the thickness of the reflector. From the result of numerical
      polarization analysis, it is showed that the five-mirror derotator has a
      significant advantage for the telescopes with a small field of view, especially
      in polarimetry at longer wavelengths.

PMID- 30114111
TI  - Fundamental figures of merit for engineering Forster resonance energy transfer.
AB  - Over the past 15 years there has been an ongoing debate regarding the influence
      of the photonic environment on Forster resonance energy transfer (FRET).
      Disparate results corresponding to enhancement, suppression and null effect of
      the photonic environment have led to a lack of consensus between the traditional
      theory of FRET and experiments. Here we show that the quantum electrodynamic
      theory (QED) of FRET near an engineered nanophotonic environment is exactly
      equivalent to an effective near-field model describing electrostatic dipole
      dipole interactions. This leads to an intuitive and rigorously exact description
      of FRET, previously unavailable, bridging the gap between experimental
      observations and theoretical interpretations. Furthermore, we show that the
      widely used concept of Purcell factor variation is only important for
      understanding spontaneous emission and is an incorrect figure of merit (FOM) for
      analyzing FRET. To this end, we analyze the figures of merit which characterize
      FRET in a photonic environment 1) the FRET rate enhancement factor (FET), 2) FRET
      efficiency enhancement factor (Feff) and 3) Two-point spectral density (SEE)
      which is the photonic property of the environment governing FRET analogous to the
      local density of states that controls spontaneous emission. Counterintuitive to
      existing knowledge, we show that suppression of the Purcell factor is in fact
      necessary for enhancing the efficiency of the FRET process. We place fundamental
      bounds on the FRET figures of merit arising from material absorption in the
      photonic environment as well as key properties of emitters including intrinsic
      quantum efficiencies and orientational dependence. Finally, we use our approach
      to conclusively explain multiple recent experiments and predict regimes where the
      FRET rate is expected to be enhanced, suppressed or remain the same. Our work
      paves for a complete theory of FRET with predictive power for designing the ideal
      photonic environment to control FRET.

PMID- 30114113
TI  - Beam shaping with a plano-freeform lens pair.
AB  - It has been shown in [Arch. Rational Mechanics and Analysis 201, 1013 (2011)].
      Such approach provides a rigorous methodology for designing freeform optics for
      irradiance redistribution. In this paper, this approach is applied to design of a
      laser beam shaping system with two lenses.

PMID- 30114112
TI  - Fast phase retrieval in off-axis digital holographic microscopy through deep
      learning.
AB  - Traditional digital holographic imaging algorithms need multiple iterations to
      obtain focused reconstructed image, which is time-consuming. In terms of phase
      retrieval, there is also the problem of phase compensation in addition to
      focusing task. Here, a new method is proposed for fast digital focus, where we
      use U-type convolutional neural network (U-net) to recover the original phase of
      microscopic samples. Generated data sets are used to simulate different degrees
      of defocused image, and verify that the U-net can restore the original phase to a
      great extent and realize phase compensation at the same time. We apply this
      method in the construction of real-time off-axis digital holographic microscope
      and obtain great breakthroughs in imaging speed.

PMID- 30114114
TI  - Multi-frequency differential absorption LIDAR system for remote sensing of CO2
      and H2O near 1.6 um.
AB  - The specifications and performance of a ground-based differential absorption
      LIDAR (light detection and ranging) system (DIAL) using an optical parametric
      oscillator (OPO) are presented. The OPO is injection-seeded with the output of a
      confocal filter cavity at frequencies generated by an electro-optic phase
      modulator (EOM) from a fixed-frequency external cavity diode laser (ECDL). The
      number of seed frequencies, frequency spacings, and duration is controlled with
      an arbitrary waveform generator (AWG) driving the EOM. Range resolved data are
      acquired using both photon current and photon counts from a hybrid detection
      system. The DIAL measurements are performed using a repeating sequence of 10
      frequencies spanning a range of 37.5 GHz near 1602.2 nm to sequentially sample
      CO2 and H2O at 10 Hz. Dry air mixing ratios of CO2 and H2O with a resolution of
      250 m and an averaging time of 10 min resulted in uncertainties as low as 6
      umol/mol (ppm) and 0.44 g/kg, respectively. Simultaneous measurements using an
      integrated path differential absorption (IPDA) LIDAR system and in situ point
      sensor calibrated to WMO (World Meteorological Organization) gas standards are
      conducted over two 10 hr nighttime periods to support traceability of the DIAL
      results. The column averaged DIAL mixing ratios agree with the IPDA LIDAR results
      to within the measured uncertainties for much of two measurement periods. Some of
      the discrepancies with the in situ point sensor results are revealed through
      trends observed in the gradients of the range resolved DIAL data.

PMID- 30114115
TI  - Watt-level 193 nm source generation based on compact collinear cascaded sum
      frequency mixing configuration.
AB  - A compact, dual-stage, collinear-cascaded sum-frequency mixing configuration is
      presented for generating 193 nm sources. Due to the less-introduced, deep
      ultraviolet optical components, the system is less prone to damage. In our proof
      of-concept experiments, a 1030 nm laser and a 1553 nm laser synchronized to each
      other were used as drivers and an average power of ~0.7 W was obtained. For
      comparison, the noncollinear configuration gave an average power of 0.77 W. The
      difference of 0.07 W is attributed to the spatial walk-off inside the cesium
      lithium borate (CLBO) crystal, confirmed by indirect visualization. A possible
      way to overcome the small gap of 0.07 W is proposed for future work.

PMID- 30114116
TI  - Bimodal grating coupler design on SOI technology for mode division multiplexing
      at 1550 nm.
AB  - In this paper, we evaluate by means of simulation and experimentally the
      simultaneous coupling of the LP01x-LP11ax fiber modes and the TE0-TE1
      nanophotonic SOI waveguide modes using a grating coupler for a two-mode fiber at
      1550 nm. Both the grating width (ranging from 10 um to 15 um) and the grating
      vertical profile have been considered in the design procedure. The optimum design
      (14 um width and 609 nm grating period) has been selected in terms of coupling
      efficiency (both LP01x-TE0 and LP11ax-TE1), compactness and tolerance to lateral
      misalignments between fiber and coupler. The LP01x-TE0 and LP11ax-TE1 modes
      achieved coupling efficiencies of 49% and 45%, respectively.

PMID- 30114117
TI  - Optical design of a prism-grating-based lenslet array integral field
      spectrometer.
AB  - The optics for an integral field spectrometer based on a lenslet array is
      described. The principle behind the integral field spectroscopy of this system is
      introduced and partial modeling of the structure of the system is developed. A
      hybrid design method from physical optics and geometrical optics is used to
      design the system. Because the functions of the optical system before and after
      the lenslet array are different, the telephoto system and the spectrograph need
      to be separated. The optical system was then optimized using a combination
      design. This method is confirmed by simulation and comparison results and can be
      used in the design of other lenslet array integral field spectrometers.

PMID- 30114118
TI  - Antireflection self-reference method based on ultrathin metallic nanofilms for
      improving terahertz reflection spectroscopy.
AB  - We present the potential of an antireflection self-reference method based on
      ultra-thin tantalum nitride (TaN) nanofilms for improving terahertz (THz)
      reflection spectroscopy. The antireflection self-reference method is proposed to
      eliminate mutual interference caused by unwanted reflections, which significantly
      interferes with the important reflection from the actual sample in THz reflection
      measurement. The antireflection self-reference model was investigated using a
      wave-impedance matching approach, and the theoretical model was verified in
      experimental studies. We experimentally demonstrated this antireflection self
      reference method can completely eliminate the effect of mutual interference,
      accurately recover the actual sample's reflection and improve THz reflection
      spectroscopy. Our method paves the way to implement a straightforward, accurate
      and efficient approach to investigate THz properties of the liquids and
      biological samples.

PMID- 30114119
TI  - High-performance thermo-optic tunable grating filters based on laterally
      supported suspended silicon ridge waveguide.
AB  - We demonstrate a novel thermally tunable grating optical filter based on
      suspended silicon ridge waveguide with low power consumption, fast response and
      relatively high mechanical stability. An enhanced power efficiency of ~300 pm/mW
      is achieved by employing isolation trench. Periodic lateral tethers and anchors
      are utilized to support the overall waveguide for maintaining mechanical
      robustness. 10%-90% rising time and falling time are measured to be 78 MUs and 52
      MUs, respectively. Simulations and experiments both indicate that the
      demonstrated device has a relatively homogeneous temperature distribution, which
      is essential for practical integrated photonic devices.

PMID- 30114120
TI  - Phase-shift evolution of the thermally-induced refractive index grating in high
      power fiber laser systems induced by pump-power variations.
AB  - A phase shift between the modal interference pattern and the thermally-induced
      refractive index grating is most likely the ultimate trigger for the damaging
      effect of transverse mode instabilities (TMI) in high-power fiber laser systems.
      By using comprehensive simulations, the creation and evolution of a thermally
      induced phase shift is explained and illustrated in detail. It is shown that such
      a phase shift can be induced by a variation of the pump power. The gained
      knowledge about the generation and evolution of the phase shift will allow for
      the development of new mitigation strategies for TMI.

PMID- 30114121
TI  - Vacuum induced transparency in metamaterials.
AB  - For the cavity-based electromagnetically induced transparent (EIT), as the
      coherent driving field is enhanced by the optical cavity, the weak probe field
      can propagate through the atomic ensemble without absorption even if the driving
      field is weak. The extreme case of vacuum in the cavity is called "vacuum-induced
      transparency" (VIT) to distinguish it from the cavity EIT. Here we construct a
      new kind of cavity made of Metamaterials, i.e. epsilon-negative (EN) and MU
      negative (MN) slabs, and study the VIT phenomena of the atomic ensemble doped
      within it. When the impedances of the MN and EN slabs are matched to each other
      and the dissipation of the material is small, it behaves as a surface plasmon
      cavity with a huge Q factor. And the VIT phenomenon in this cavity appears. By
      adjusting the position of atoms, the coupling strength between the atom and the
      structure could be changed. Two kinds of extremes of VIT, the coherent population
      trapping (CPT) and the Autler-Townes splitting (ATS), can be achieved in this
      system easily. Our proposal could be used in the realization of ultra-strong
      coupling and integrated devices on quantum memory or optical switch.

PMID- 30114122
TI  - Free-space optical wiretap channel and experimental secret key agreement in 7.8
      km terrestrial link.
AB  - Secret key agreement using physical properties of a wireless channel is becoming
      a promising scheme to establish a secret key between two users, especially in
      short-distance radio frequency (RF) communications. In this scheme, the existence
      of codes or key distillation that can make the leaked information to an
      eavesdropper arbitrarily small can be derived in an information theoretical way,
      given a priori knowledge on the channel linking a sender (Alice), a legitimate
      receiver (Bob), and an eavesdropper (Eve), which is called the wiretap channel.
      In practice, however, it is often difficult for Alice and Bob to get sufficient
      knowledge on Eve. In this study, we implement a free-space optical wiretap
      channel in a 7.8 km-terrestrial link and study how to estimate Eve's tapping
      ability, demonstrating high speed secret key agreement in the optical domain
      under a certain restricted condition of line-of-sight.

PMID- 30114123
TI  - Performance optimization of 193 nm antireflective coatings with wide incident
      angle ranges on strongly curved spherical substrates.
AB  - A method to optimize the spectral performance of 193 nm antireflective (AR)
      coating with a broad range of angle of incidence (AOI) on strongly curved
      spherical substrates is described. In this method, the actual film thickness on
      test plates for single-layer LaF3 and MgF2 films are corrected by measuring the
      relationship between the film thickness on test plates and that on quartz crystal
      microbalance. Interface roughness in multi-layer AR coating is obtained from
      atomic force microscopy measurements and its effect on the spectrum of the multi
      layer is taken into account in this method by being simulated as a homogeneous
      sublayer. Porosities of the sublayers in AR coatings are obtained by reversely
      engineering the residual reflectance of the coatings/substrate/coating stacks.
      The obtained refractive indices and thicknesses in the multilayer are then used
      for analysis and optimization of the spectrum of 193 nm AR coatings. For strongly
      curved spherical surfaces, spectrum uniformity of the AR coating is optimized by
      taking into consideration simultaneously the merit functions at different
      positions of spherical substrates. This work provides a general solution to the
      performance optimization of 193 nm AR coatings with broad AOI range and on
      strongly curved spherical substrates.

PMID- 30114124
TI  - Line-edge roughness as a challenge for high-performance wire grid polarizers in
      the far ultraviolet and beyond.
AB  - High-performance nano-optical elements for application wavelengths in the
      ultraviolet spectral range often require feature sizes of only a few tens of
      nanometers where line edge roughness (LER) becomes a critical parameter for the
      optical performance. In this contribution, we explore the influence of LER on the
      optical performance of wire grid polarizers (WGP) in the far ultraviolet range.
      Therefore, we present a method, which uses the finite difference time domain
      method in combination with a comprehensive spatial frequency dependent LER model.
      The measured LER of 3.6 nm (standard deviation) reduces the WGP's extinction
      ratio by a factor of 3.6 at a wavelength of 248 nm. We identify a critical range
      of the correlation length, which maximizes the detrimental effect of LER. The
      presented method and the results provide the basis for future fabrication
      technology optimization of WGPs and other optical meta-surfaces in the
      ultraviolet spectral region or at even shorter wavelengths.

PMID- 30114125
TI  - Demonstration of color display metasurfaces via immersion lithography on a 12
      inch silicon wafer.
AB  - The demonstration of a color display metasurface on a 12-inch silicon wafer with
      critical dimension (CD) below 100 nm by complementary metal-oxide semiconductor
      (CMOS) compatible technology is reported for the first time. The 193 nm ArF deep
      UV immersion lithography is leveraged instead of electron beam lithography (EBL)
      to pattern the metasurface, which greatly improves the efficiency while keeping a
      high resolution. The demonstrated metasurface successfully generates the resonant
      modes and reflects the lights at resonance wavelengths, giving its display in
      red, green, and blue (RGB) colors. The wafer-level uniformities of CD and
      reflection characteristic of the metasurface are measured and analyzed. The
      experimental data show that they are well controlled in the fabrication process.
      The work provides a promising route towards mass production of dielectric
      metasurfaces.

PMID- 30114126
TI  - Theory of microscopic meta-surface waves based on catenary optical fields and
      dispersion.
AB  - Surface waves bounded by subwavelength-structured surfaces have many exotic
      electromagnetic properties different from those supported by smooth surfaces.
      However, there is a long-standing misconception, claiming that these waves must
      propagate along the macroscopic interface. In this paper, we describe in detail
      the microscopic meta-surface wave (M-wave) in artificial subwavelength
      structures. It is shown that the waves penetrating macroscopic surfaces share the
      essence of most surface waves (i.e., they spread along the microscopic
      interfaces, formed by adjacent constitutive materials). Equivalent circuit theory
      and transfer matrix method have been adopted to quantitatively describe these M
      waves with high accuracy in the form of catenary optical fields and dispersion.
      Based on these analyses, novel omnidirectional band-stop filters and wide-angle
      beam deflectors are designed with operational angles up to 88 degrees . We
      believe these results may provide many new perspectives for both the
      understanding and design of functional subwavelength structures.

PMID- 30114127
TI  - Hadamard transform-based calibration method for programmable optical filters
      based on digital micro-mirror device.
AB  - Digital micromirror device (DMD) based optical filters provide a new avenue for
      spectral modulation in many research applications. Traditional sequential channel
      scanning method for the calibration of such filters may suffer from compromised
      spectral tuning accuracy due to the signal to noise ratio restriction on the
      minimum pixel number of each channel. In this work, we propose a Hadamard
      transform based calibration method to address this issue. A DMD-based
      programmable optical filter is constructed and calibrated using both the
      sequential scanning method and the proposed method for the subsequent synthesis
      of three representative filters (i.e., the bandpass filter, Gaussian filter, and
      principal component based filter). The spectral tuning accuracy is evaluated by
      calculating the relative root mean square error (RMSE) between the synthesized
      transmittance spectrum and the target spectrum. The results show that when
      calibrated with the proposed method, the programmable filter exhibits a
      consistent decrease in the relative RMSE with an increasing channel number for
      all filters. The smallest relative RMSE values are therefore achieved when each
      channel contains only one DMD pixel. In contrast, for the sequential scanning
      method, the relative RMSE increases dramatically when each channel contains three
      or fewer DMD pixels. This suggests that our method is superior to the sequential
      scanning method in spectral tuning accuracy when the signal level is low.

PMID- 30114128
TI  - Cascaded DBR plasmonic cavity lens for far-field subwavelength imaging at a
      visible wavelength.
AB  - We experimentally demonstrate a novel cascaded plasmonic superlens, which can
      directly image subwavelength objects with magnification in the far field at a
      wavelength of 640nm. The lens consists of two plasmonic slabs. One is a plasmonic
      cavity lens used for near-field coupling, and the other one is a planar plasmonic
      lens for phase compensation and thus, image magnification. To tune the
      performance wavelength to visible and to enhance the near-field transmission,
      distributed Bragg reflectors are integrated to the plasmonic cavity lens around
      the lens center, forming additional lateral cavities for surface waves. In this
      article, we first show numerical results about the working principle and the
      performance of the lens. Then, we demonstrate the imaging performance of a
      fabricated superlens experimentally. The fabricated superlens exhibits a lateral
      resolution down to 200 nm at the wavelength of 640 nm observed in the far field.
      Compared to our earlier design, shift invariance is achieved with the current
      approach. Our results could open a way for designing and fabricating novel
      miniaturized plasmonic superlenses in the future.

PMID- 30114129
TI  - Quantum metrology beyond Heisenberg limit with entangled matter wave solitons.
AB  - Considering matter wave bright solitons from weakly coupled Bose-Einstein
      condensates trapped in a double-well potential, we study the formation of
      macroscopic non-classical states, including Schrodinger-cat superposition state
      and maximally path entangled N00N-state. We examine these macroscopic states by
      Mach-Zehnder interferometer in the context of parity measurements, which has been
      done to obtain Heisenberg limit accuracy for linear phase shift measurement. We
      reveal that the ratio of two-body scattering length to intra-well hopping
      parameter can be measured with the scaling beyond this limit by using nonlinear
      phase shift with interacting quantum solitons.

PMID- 30114130
TI  - Signal reshaping and noise suppression using photonic crystal Fano structures.
AB  - We experimentally demonstrate the use of photonic crystal Fano resonances for
      reshaping optical data signals. We show that the combination of an asymmetric
      Fano resonance and carrier-induced nonlinear effects in a nanocavity can be used
      to realize a nonlinear power transfer function, which is a key functionality for
      optical signal regeneration, particularly for suppression of amplitude
      fluctuations of data signals. The experimental results are explained using
      simulations based on coupled-mode theory and also compared to the case of using
      conventional Lorentzian-shaped resonances. Using indium phosphide photonic
      crystal membrane structures, we demonstrate reshaping of 2 Gbit/s and 10 Gbit/s
      return-to-zero on-off keying (RZ-OOK) data signals at telecom wavelengths around
      1550 nm. Eye diagrams of the reshaped signals show that amplitude noise
      fluctuations can be significantly suppressed. The reshaped signals are
      quantitatively analyzed using bit-error ratio (BER) measurements, which show up
      to 2 dB receiver sensitivity improvement at a BER of 10-9 compared to a degraded
      input noisy signal. Due to efficient light-matter interaction in the high-quality
      factor and small mode-volume photonic crystal nanocavity, low energy consumption,
      down to 104 fJ/bit and 41 fJ/bit for 2 Gbit/s and 10 Gbit/s, respectively, has
      been achieved. Device perspectives and limitations are discussed.

PMID- 30114131
TI  - Self-trapped pulsed beams with finite power in Kerr media excited by time
      diffracting, space-time beams.
AB  - We study the nonlinear propagation of space-time pulsed beams, also known as time
      diffracting beams, a recently introduced class of diffraction-free spatiotemporal
      wave packets whose temporal-transversal structure is that of diffraction in time.
      We report on the spontaneous formation of propagation-invariant, spatiotemporally
      compressed pulsed beams carrying finite power from exciting time-diffracting
      Gaussian beams in media with cubic Kerr nonlinearity at powers below the critical
      power for collapse, and also with other collapse-arresting nonlinearities above
      the critical power. Their attraction property makes the experimental observation
      of the self-trapped pulsed beams in cubic Kerr media feasible. The structure in
      the temporal and transversal dimensions of the self-trapped wave packets is shown
      to be the same as the structure in the axial and transversal dimensions of the
      self-focusing and (arrested) collapse of monochromatic Gaussian beams.

PMID- 30114132
TI  - Electro-wetting lenticular lens with improved diopter for 2D and 3D conversion
      using lens-shaped ETPTA chamber.
AB  - In this paper, we introduce a method for improving the lens diopter of 2D/3D
      convertible devices using electro-wetting. For stable operation, an electro
      wetting device requires high dioptric performance and this was achieved using bi
      convex liquid-liquid-solid phases. 1-Chloronaphthalene with a refractive index of
      1.633 was used as an oil phase to achieve high diopters. ETPTA
      (trimethylolpropane ethoxylate triacrylate), a UV-sensitive material with low
      chemical reactivity to the 1-Chloronaphthalene, was used as a chamber material.
      This resulted in a diopter of 3030D for high quality multi-view images without
      unstable oil movement or trembling. The ETPTA was molded on a 0.3mm thick glass
      substrate that was coated with UV adhesive (NOA 81). The maximum diopter capable
      of stable operation was 3425D. 2D and 3D conversion and parallax motion were
      demonstrated.

PMID- 30114133
TI  - Linearly chirped mid-infrared supercontinuum in all-normal-dispersion
      chalcogenide photonic crystal fibers.
AB  - We demonstrate all-normal dispersion supercontinuum generation in chalcogenide
      photonic crystal fibers pumped at 2070-2080 nm with a femtosecond fiber laser. At
      2.9 kW peak power, the generated supercontinuum has a 3 dB bandwidth of 27.6 THz
      and -20 dB bandwidth of 75.5 THz. We experimentally investigated the
      supercontinuum evolution inside our sample fiber at various peak powers and fiber
      lengths and study the impact of fiber water absorption on the generated
      supercontinuum spectrum. Multiple tests with fiber length- ranging from 0.34 to
      10 cm-provide insight on pulse evolution along fiber length. Our simulations,
      which utilizes the generalized nonlinear Schrodinger equation model, match
      perfectly the experiments for all tested pump powers and fiber lengths, and
      confirm that the output pulse has a linear chirp, allowing linear pulse
      compression.

PMID- 30114134
TI  - Investigation of the long wavelength limit of soliton self-frequency shift in a
      silica fiber.
AB  - We explore the long wavelength limit of soliton self-frequency shift in silica
      based fibers experimentally and using numerical simulation. We found that the
      longest wavelength soliton generated by soliton self-frequency shift is
      approximately 2500 nm because the soliton loses its energy rapidly at wavelength
      beyond 2400 nm due to material absorption by silica and water. We demonstrate
      1580-2520 nm wavelength-tunable, high-pulse energy soliton generation using
      soliton self-frequency shift in a large-mode-area silica fiber pumped by a
      compact fiber source. Soliton pulses with pulse width of ~100 fs and pulse energy
      up to 73 nJ were obtained. Second harmonic generation of the solitons enables a
      wavelength-tunable femtosecond source from 950 nm to 1260 nm, with pulse energy
      up to 21 nJ. Using such energetic pulses, we demonstrate in vivo two-photon
      excited fluorescence imaging of vasculature and neurons in a mouse brain at
      wavelength beyond the tuning range of a mode-locked Ti:Sapphire lasers.

PMID- 30114135
TI  - Designing MMI structured beam-splitter in LiNbO3 crystal based on a combination
      of ion implantation and femtosecond laser ablation.
AB  - In this work, the design and numerical study of a MMI-based LiNbO3 beam splitter
      were presented, with a combination of ion implantation and femtosecond laser
      ablation as a fabricating strategy. The designed splitters show advantages such
      as good fabrication tolerance, low insertion loss, compactness, and simple
      fabrication processes. We also demonstrated that the self-imaging principle could
      be applied to design low-loss MMI beam splitters for multi-mode input with mode
      number m = 1 and n>1 by carefully choosing the geometry parameters. The presented
      fabrication strategy provides an alternative choice for the fabrication of power
      splitters also with other MMI-based devices in various optical monocrystal chips.

PMID- 30114136
TI  - Experimental demonstration of indoor uplink near-infrared LED camera
      communication.
AB  - In this paper, we present experimental demonstration of an indoor uplink near
      infrared LED camera communication (ICC) that employs near-infrared (IR) light as
      a communication medium and a camera as the receiver. The proposed ICC exploits
      advantages of the camera receiver to provide wider coverage and accurate indoor
      positioning in IR communications. Since near-IR light is the communication
      medium, ICC can safely increase the light intensity compared with other visible
      light based wireless communication schemes. Unlike previous studies focused on
      positioning only, the ICC provides practical uplink indoor wireless communication
      as well as positioning. As in optical camera communications, the blooming effect
      from slow speed cameras needs to be mitigated in the ICC. An adaptive intensity
      compensation algorithm is also proposed for reducing this blooming effect. The
      blooming reduction algorithm is based on the absence of visible light
      interference in IR communications. Experiments demonstrate that employing an even
      low-specification webcam and low-power LEDs can provide centimeter-scale accuracy
      for the user positioning and a data rate of 6.72 kbit/s at a distance of 100 cm.

PMID- 30114137
TI  - Mechanism of single-shot damage of Ru thin films irradiated by femtosecond
      extreme UV free-electron laser.
AB  - Ruthenium is a perspective material to be used for XUV mirrors at free-electron
      laser facilities. Yet, it is still poorly studied in the context of ultrafast
      laser-matter interaction. In this work, we present single-shot damage studies of
      thin Ru films irradiated by femtosecond XUV free-electron laser pulses at FLASH.
      Ex-situ analysis of the damaged spots, performed by different types of
      microscopy, shows that the weakest detected damage is surface roughening. For
      higher fluences we observe ablation of Ru. Combined simulations using Monte-Carlo
      code XCASCADE(3D) and the two-temperature model reveal that the damage mechanism
      is photomechanical spallation, similar to the case of irradiating the target with
      optical lasers. The analogy with the optical damage studies enables us to explain
      the observed damage morphologies.

PMID- 30114138
TI  - Polarization division multiplexing pulse coding for eliminating the effect of
      polarization pulling in Golay-coded BOTDA fiber sensor.
AB  - An approach to eliminating the effect of polarization pulling in Golay-coded
      Brillouin optical time domain analysis (BOTDA) fiber sensor by employing
      polarization division multiplexing (PDM) pulse coding is presented. Three
      different schemes, including polarization switching, polarization scrambling, and
      PDM pulse coding are implemented and compared. Experimental results indicate that
      sensing stability is enhanced by ~2.5 times using the proposed scheme.

PMID- 30114139
TI  - Refractive-index-sensing optical comb based on photonic radio-frequency
      conversion with intracavity multi-mode interference fiber sensor.
AB  - Optical frequency combs (OFCs) have attracted attention as optical frequency
      rulers due to their tooth-like discrete spectra together with their inherent mode
      locking nature and phase-locking control to a frequency standard. Based on this
      concept, their applications until now have been demonstrated in the fields of
      optical frequency metrology. However, if the utility of OFCs can be further
      expanded beyond their application by exploiting new aspects of OFCs, this will
      lead to new developments in optical metrology and instrumentation. Here, we
      report a fiber sensing application of OFCs based on a coherent link between the
      optical and radio frequencies, enabling high-precision refractive index
      measurement based on frequency measurement in radio-frequency (RF) region. Our
      technique encodes a refractive index change of a liquid sample into a repetition
      frequency of OFC by a combination of an intracavity multi-mode-interference fiber
      sensor and wavelength dispersion of a cavity fiber. Then, the change in
      refractive index is read out by measuring the repetition frequency in RF region
      based on a frequency standard. Use of an OFC as a photonic RF converter will lead
      to the development of new applications in high-precision fiber sensing with the
      help of functional fiber sensors and precise RF measurement.

PMID- 30114140
TI  - Effect of PVA coating on the electric field intensity distribution and laser
      damage performance of fused silica optics surfaces.
AB  - A facile method was proposed to enhance the laser damage performance of the fused
      silica optics by coating a PVA film on the rear surface of the optics. FDTD
      simulation result suggests that the PVA coating with suitable thickness can
      transfer the maximal electric field intensity from the rear surface to the
      interface between the coating and air, and reduce the electric field intensity of
      the rear surface remarkably. LIDT tests reveal that the LIDT of fused silica with
      PVA coating changed periodically with respect to the coating thickness, which
      agrees well with the tendency predicted by FDTD simulation. Finally, PVA coatings
      with a thickness of 60 nm and 300 nm can both improve the LIDT of AMP-treated
      fused silica by ~20%, which provide a potential to be applied in high power laser
      facility.

PMID- 30114141
TI  - Subwavelength resolution scanning diffracted-light microscopy using plasmonic
      ultra-thin condensers.
AB  - We used a rotating slit placed at the back focal plane of the microscope's
      objective lens to scan the light diffracted by a plasmonic crystal, which had a
      period smaller than the resolution limit of the optical microscope. A set of
      images were collected at different orientations of the slit. A high-resolution
      image of the plasmonic crystal was obtained by processing the experimental images
      using a numerical Fourier ptychographic algorithm. Supporting simulations of the
      experiments are also presented.

PMID- 30114142
TI  - Interferometric detection of 3D motion using computational subapertures in
      optical coherence tomography.
AB  - Doppler optical coherence tomography (OCT) quantifies axial motion with high
      precision, whereas lateral motion cannot be detected by a mere evaluation of
      phase changes. This problem was solved by the introduction of three-beam Doppler
      OCT, which, however, entails a high experimental effort. Here, we present the
      numerical analogue to this experimental approach. Phase-stable complex-valued OCT
      datasets, recorded with full-field swept-source OCT, are filtered in the Fourier
      domain to limit imaging to different computational subapertures. These are used
      to calculate all three components of the motion vector with interferometric
      precision. As known from conventional Doppler OCT for axial motion only, the
      achievable accuracy exceeds the actual imaging resolution by orders of magnitude
      in all three dimensions. The feasibility of this method is first demonstrated by
      quantifying micro-rotation of a scattering sample. Subsequently, a potential
      application is explored by recording the 3D motion vector field of tissue during
      laser photocoagulation in ex-vivo porcine retina.

PMID- 30114143
TI  - Real-time 20.37 Gb/s optical OFDM receiver for PON IM/DD systems.
AB  - This paper presents the hardware architecture of an OFDM receiver suitable for
      optical communications. The receiver has been implemented in an FPGA device and
      used to demonstrate experimentally an optical OFDM transmission in a passive
      optical link with a directly modulated DFB laser and DAC/ADC at 5 GS/s. A bit
      rate of 20.37 Gb/s is achieved using an OFDM signal with subcarrier modulation
      format up to 512-QAM, it has been successfully transmitted over 10 km SSMF with a
      spectral efficiency of 8.38 bit/s/Hz.

PMID- 30114144
TI  - Oblique propagation of light through a thick, space-variant birefringent element.
AB  - Understanding and modeling the propagation of polarized light through thick,
      space variant birefringent media is important in both fundamental and applied
      optics. We present and experimentally evaluate two methods to model the off axis
      propagation of polarized light through a thick stress-engineered optic (SEO).
      First, we use a differential equation solving method, which utilizes the analytic
      expression for the Jones matrix of the SEO leading to a numerical solution for
      the output electric field. Then we present a geometric method to obtain similar
      results with much less computational complexity. Finally, a comparison is done
      between the data and the simulations.

PMID- 30114145
TI  - Effective heat dissipation in an adiabatic near-field transducer for HAMR.
AB  - To achieve a feasible heat-assisted magnetic recording (HAMR) system, a near
      field transducer (NFT) is necessary to strongly focus the optical field to a
      lateral region measuring tens of nanometres in size. An NFT must deliver
      sufficient power to the recording medium as well as maintain its structural
      integrity. The self-heating problem in the NFT causes materials failure that
      leads to the degradation of the hard disk drive performance. The literature
      reports NFT structures with physical sizes well below 1 micron which were found
      to be thermo-mechanically unstable at an elevated temperature. In this paper, we
      demonstrate an adiabatic NFT to address the central challenge of thermal
      engineering for a HAMR system. The NFT is formed by an isosceles triangular gold
      taper plasmonic waveguide with a length of 6 um and a height of 50 nm. Our study
      shows that in the full optically and thermally optimized system, the NFT
      efficiently extracts the incident light from the waveguide core and can improve
      the shape of the heating source profile for data recording. The most important
      insight of the thermal performance is that the recording medium can be heated up
      to 866 K with an input power of 8.5 mW which is above the Curie temperature of
      the FePt film while maintaining the temperature in the NFT at 390 K without a
      heat spreader. A very good thermal efficiency of 5.91 is achieved also. The
      proposed structure is easily fabricated and can potentially reduce the NFT
      deformation at a high recording temperature making it suitable for practical HAMR
      application.

PMID- 30114146
TI  - Broadband Fourier-transform coherent Raman spectroscopy with an ytterbium fiber
      laser.
AB  - We demonstrate a Fourier transform (FT) coherent anti-Stokes Raman scattering
      (CARS) spectroscopy system based on fiber technology with ultra-broad spectral
      coverage and high-sensitivity. A femtosecond ytterbium fiber oscillator is
      amplified and spectrally broadened in a photonic crystal fiber to synthesize
      pulses with energy of 14 nJ at 1040 nm, that are compressed to durations below 20
      fs. The resulting pulse train is coupled to a FT-CARS interferometer enabling
      measurement of high-quality CARS spectra with Raman shifts of ~3000 cm-1 and
      signal to noise ratio up to 240 and 690 with acetonitrile and polystyrene
      samples, respectively, for observation times of 160 us; a detection limit of one
      part per thousand is demonstrated with a cyanide/water solution. The system has
      the potential to detect trace contaminants in water as well as other broadband
      high-sensitivity CARS spectroscopy applications.

PMID- 30114147
TI  - Calibration of an in-water multi-excitation fluorometer for the measurement of
      phytoplankton chlorophyll-a fluorescence quantum yield.
AB  - A multi-excitation fluorometer (MFL, JFE Advantech Co., Ltd.), originally
      designed to discriminate between phytoplankton species present within a
      population, has been redirected for use in fluorescence quantum yield (FQY)
      determination. While this calibration for apparent FQY requires no modification
      of the MFL, it is necessary to have an independent measurement of the spectral
      absorption coefficient of the subject fluid. Two different approaches to
      calibration were implemented. The primary method made use of reference
      fluorescent dye solutions of known quantum yield. The second method made use of
      acrylic fluorescent plaques and films. The two methods yielded consistent
      results, except in the 570 and 590 nm LED channels of the MFL. Application of the
      MFL in FQY determination is illustrated with an in situ Southern Ocean sample.

PMID- 30114148
TI  - Efficient and robust recurrence relations for the Zernike circle polynomials and
      their derivatives in Cartesian coordinates.
AB  - For some time it has been known and recommended that the calculation of Zernike
      polynomials to radial orders higher than 8 to 10 should be performed using
      recurrence relations rather than explicit expressions due increasingly large
      cancellation errors. This paper presents a set of simple recurrence relations
      that can be used for the unit-normalized Zernike polynomials in polar coordinates
      and easily adapted to Cartesian coordinates as well. The recurrence relations are
      also well suited for the calculation of the Cartesian derivatives of the Zernike
      polynomials. The recurrence relations are easily extended to arbitrarily high
      orders. Assessments of the precision achievable with standard 64-bit floating
      point arithmetic show that Zernike polynomials up to radial order 30 can be
      calculated over the unit disc with errors not exceeding 5E-14, and up to radial
      order 50 with errors not exceeding 1.2E-13. Comparison with the Zernike
      capability in OpticStudio (Zemax) shows that the recurrence relations are
      superior in performance (both speed and precision) over the existing algorithm
      implemented in the software. General pseudo-code for the calculation of Zernike
      polynomials and their derivatives is also presented.

PMID- 30114149
TI  - Free-space quantum key distribution in urban daylight with the SPGD algorithm
      control of a deformable mirror.
AB  - Free-space quantum key distribution (QKD) is important to realize a global-scale
      quantum communication network. However, performing QKD in daylight against the
      strong background light noise is a major challenge. Here, we develop the
      stochastic parallel gradient descent (SPGD) algorithm with a deformable mirror to
      improve the signal-to-noise ratio (SNR). We then experimentally demonstrate free
      space QKD in the presence of urban daylight. The final secure key rate of the QKD
      is 98~419 bps throughout the majority of the daylight hours.

PMID- 30114150
TI  - Optically tunable spin texture of the surface state for Bi2Se3 and SmB6
      topological insulators.
AB  - The spin texture of the surface state for topological insulators can be
      manipulated by the polarization of light, which might play a potential role in
      the applications in spintronics. However, the study so far in this direction
      mainly focuses on the classical light-topological-insulators interactions; TIs
      coupled to quantized light remains barely explored. In this paper, we develop a
      formalism to deal with this issue of spin texture of the surface state for
      topological insulators (for example Bi2Se3 and SmB6) irradiated by a quantum
      field, and we find that the coupling between an electron and a single-mode
      quantum field modulates only the arrow length that represents the spin
      polarization of a topological surface state. Specifically, when the photon number
      of a single-mode quantum field is fixed, the azimuth angle between the quantum
      light and the material surface manipulates the spin textures along the constant
      energy contour rotating (clockwise or counterclockwise) around the high symmetry
      point, and the polar angle controls the magnitude of the spin polarization. These
      results are quite different from the situation where an external field is not
      applied to an electron in a crystal or where a classical external field is
      utilized to control the spin polarization of a photoemitted electron in a vacuum.
      Our results have potential applications in quantum optics and condensed-matter
      physics.

PMID- 30114151
TI  - Temperature and liquid refractive index sensor using P-D fiber structure-based
      Sagnac loop.
AB  - A cost-efficient P-D fiber structure-based Sagnac loop sensor is proposed and
      experimentally demonstrated for measuring temperature and liquid refractive index
      (RI). The P-D structure is fabricated by fusion splicing a section of
      polarization-maintaining fiber (PMF) to a piece of multimode D-shaped optical
      fiber (MMDF). Then the P-D structure is built into a Sagnac loop using a 3dB
      coupler. The temperature and RI characteristics of the sensor are investigated
      experimentally. The results show that two resonant dips have different spectral
      responses of temperature and RI, which indicate that the sensor can realize
      simultaneous temperature and RI measurement. The high sensitivities of -1.804nm/
      degrees C and -131.49nm/RIU are achieved. The obtained resolutions of temperature
      and RI of the proposed sensor can reach 0.01 degrees C and 2.46 * 10-4RIU,
      respectively. The proposed sensor has the potential application in biological and
      chemical fields.

PMID- 30114152
TI  - Fiducial-aided on-machine positioning method for precision manufacturing of
      optical freeform surfaces.
AB  - There are still significant challenges in the accurate positioning of optical
      freeform surfaces on the machine tool and the measurement instrument due to the
      high accuracy requirement and their complex shapes. This paper proposes a
      Fiducial-aided On-machine Positioning method (FAOPM) that combines on-machine
      measurement and off-machine measurement to precisely position optical freeform
      surfaces during the precision manufacturing cycle including rough machining, fine
      machining, measurement, and error compensation. The FAOPM makes use of fiducials
      which are firstly measured on a coordinate measuring machine with nanometric
      accuracy to generate a Fiducial-aided Computer Aided Design (FA-CAD) of the
      designed optical surface, then the developed on-machine measuring device obtains
      the accurate positions of the fiducials after remounting in the machining
      coordinate system. Finally the relative position of the workpiece is identified
      so that the associated cutting paths and compensation tool path can be easily
      generated. Several optical freeform surfaces were experimentally machined to
      prove the capability of the proposed method. The results indicate that the
      positions of the workpiece during the precision manufacturing and measurement
      cycle were precisely achieved and the form accuracy of the optical freeform
      surfaces was remarkable improved based on the FAOPM.

PMID- 30114153
TI  - Theoretical and experimental study of the color of ghost imaging.
AB  - In this article, the color of ghost imaging (GI) was studied theoretically and
      experimentally. The theoretical analysis and experimental data show that the
      color of GI with rotating ground glass plate and computational GI are the same as
      the light source. If multiwavelength source is used in these schemes, a full
      color image without distortion can be obtained. In contrast, the color of GI with
      spatial light modulator as well as that in a quantum system is a superimposed
      one, depending on the idle and object light beams, and following the principle of
      light color superposition. Correspondingly, a full color image can also be
      obtained under the condition of multiwavelength source, but with color distortion
      existing.

PMID- 30114154
TI  - Experimental realization of Heisenberg-limit resolution imaging through a phase
      controlled screen with classical light.
AB  - By using a dynamically phase-controlled screen proposed in [Opt. Express 25,
      22789 (2017)], we demonstrated experimentally a correlation imaging scheme with
      its spatial resolution reaching the fundamental Heisenberg limit. In the
      experiments, the dynamically phase-controlled screen was realized through a
      commercial spatial light modulator by dynamically loading computer generated
      phase patterns, and the scanning-focused-beam illumination mode was employed to
      achieve the Heisenberg-resolution imaging with classical light such as laser and
      pseudo-thermal light.

PMID- 30114155
TI  - Investigation of residual amplitude modulation in squeezed state generation
      system.
AB  - We present an analysis on how the optical parametric oscillator (OPO) detuning
      and the relative phase drift deteriorate the stability of the squeezed states,
      including the output power and the squeezed degree, and investigate the influence
      of RAM on the cavity detuning and the relative phase drift under different cases.
      Subsequently, the RAM is experimentally measured. In term of the measurement
      results, we perform a comparative study about RAM's influence on the cavity and
      phase locking in two cases. As a result, with the error signal extracted from the
      transmission of the OPO, the output power stability of the squeezed light is
      greatly improved. With the phase modulation imposed on the signal beam, the long
      term stability of the squeezed degree is significantly enhanced.

PMID- 30114156
TI  - Independent amplitude and trajectory/beam-width control of nonparaxial beams.
AB  - We show that it is possible to generate non-paraxial optical beams with pre
      engineered trajectories and designed maximum amplitude along these trajectories.
      The independent control of these two degrees of freedom is made possible by
      engineering both the amplitude and the phase of the optical wave on the input
      plane. Furthermore, we come to the elegant conclusion that the beam width depends
      solely on the local curvature of the trajectory. Thus, we can generate beams with
      pre-defined amplitude and beam-width by appropriately selecting the local
      curvature. Our theoretical results are in excellent agreement with numerical
      simulations. We discuss about methods that can be utilized to experimentally
      generate such beam. Our work might be useful in applications where precise beam
      control is important such as particle manipulation, filamentation, and
      micromachining.

PMID- 30114157
TI  - Systematic spectral shifts in the mid-infrared spectroscopy of aerosols.
AB  - Infrared spectroscopy in the spectral fingerprint region from 6.5 to 20 um has
      been applied for decades to identify vapor- and condensed-phase chemicals with
      high confidence. By employing a unique broadband laser operating from 7.2- to
      11.5-um we show that, in this region, wavelength-dependent Mie-scattering effects
      substantially modulate the underlying chemical absorption signature, undermining
      the ability of conventional infrared absorption spectroscopy to identify
      aerosolized liquids and solids. In the aerosol studied, Mie theory predicts that
      the positions of spectroscopic features will blue-shift by up to 200 nm, and this
      behavior is confirmed by experiment, illustrating the critical importance of
      considering Mie contributions to aerosol spectroscopy in the mid infrared. By
      examining the spectroscopy of light scattered from an aerosol of the chemical
      diethyl phthalate, we demonstrate excellent agreement with a Mie-scattering model
      informed by direct measurements of the particle-size-distribution and complex
      refractive index.

PMID- 30114158
TI  - Label-free real-time detection of biotinylated bovine serum albumin using a low
      cost optical cavity-based biosensor.
AB  - We have developed a low-cost optical cavity-based biosensor with a differential
      detection method for point-of-care medical diagnostics. To experimentally
      demonstrate its label-free real-time biosensing capability, we performed the
      detection of biotinylated bovine serum albumin (BSA). Streptavidin is introduced
      into the optical cavity structure and immobilized on 3-aminopropyltriethoxysilane
      (APTES) coated surface. After rinsing out unbound streptavidin with DI water,
      biotinylated BSA without any labeling is introduced. A CMOS camera captures the
      transmitted light of two different wavelengths passing through the optical cavity
      sensing area in real-time. Then, the differential values are calculated to
      enhance the responsivity. We successfully demonstrated the label-free real-time
      detection of biotinylated BSA, and the measurement results matched well with the
      simulation results. The limit of detection of the optical cavity-based biosensor
      for the biotinylated BSA detection with the sensing area of 180 MUm * 180 MUm is
      estimated to be 2.82 pM, which could be reduced further for a smaller sensing
      area with the tradeoff of a longer sensing time.

PMID- 30114159
TI  - Characterizing the effect of femtosecond photo-treatment on the center wavelength
      of fiber Bragg gratings.
AB  - Various types of pre- and post-treatments to optical fibers are typically used to
      improve and/or change the properties of fiber Bragg grating (FBG). Here, we
      investigate experimentally the effects of NIR femtosecond (fs) laser pulses used
      for pre- and post-treatment on the refractive index of the fiber, and the
      resulting center wavelength shift of an fs inscribed FBG. We observe "red"-shift
      when applying a suitable pre-treatment, and both "blue"- and "red"-shifts when
      applying post-treatment. We characterize the photo-treatment parameters and
      compare to an FBG inscribed on a fresh fiber without any treatment. We also show
      that when the photo-treatment is saturated the result is a phase-shifted grating.
      Our results give further insight into the process of fs photo-treatments and
      quantify the effects in the case of fs FBG inscription.

PMID- 30114160
TI  - Fabrication of ordered hierarchical structures on stainless steel by picosecond
      laser for modified wettability applications.
AB  - Ordered hierarchical structures were fabricated on a stainless steel surface
      using a single picosecond laser for highly controllable dimensions. Picosecond
      laser induced periodic structures were firstly used to create large-scale nano
      structures with a period of ~450 nm. Subsequently, laser direct writing, by
      simply changing process parameters was employed to create micro squared
      structures with 19 MUm width, 19 MUm interval and 3-7.5 MUm depth on the
      previously created nano-structures. As a result, micro squared structures covered
      by uniform nano-structures, similar to examples present in nature, were
      successfully fabricated. Additionally, the wettability of the created
      hierarchical structures was analyzed. The results demonstrated that the
      combination of both micro- and nano-structures allowed to tune the wetting
      behavior, presenting a great potential for wettability applications.

PMID- 30114161
TI  - High-resolution stigmatic spectrograph for a wavelength range of 12.5-30 nm.
AB  - We describe a broadband (12.5-30 nm) extreme ultraviolet (XUV) spectrograph,
      which is stigmatic throughout its operating range. The instrument employs a near
      normal-incidence aperiodic Mo/Si multilayer mirror and a grazing-incidence plane
      varied line-space (VLS) grating. Strict stigmatism is fulfilled simultaneously at
      two wavelengths and the condition of practical stigmatism is fulfilled over two
      octaves in wavelength. The vertically space-resolved line spectra of multiple
      charge ions from laser plasma were recorded to demonstrate a spectral resolving
      power of 103 and a spatial resolution of ~26 MUm, both figures corresponding to
      two detector pixels. The electron density was evaluated from the Stark broadening
      of the Balmer line Hbeta (135 A) of C VI in the plasma excited by 0.5 J, 8 ns,
      1.06 MUm pulses.

PMID- 30114162
TI  - Bidirectional long-reach PON using Kramers-Kronig-based receiver for Rayleigh
      Backscattering noise and SSBI interference elimination.
AB  - In this paper, a novel bidirectional long-reach PON is proposed and demonstrated
      by using Kramers-Kronig (KK)-based receiver and 7-core fiber to simultaneously
      cope with the induced signal-signal beating interference (SSBI) and Rayleigh
      backscattering (RB) noises. A low-cost self-homodyne detection using only one PD
      is used at both OLT and ONU, and the middle core of 7-core fiber is used to
      deliver the seed light to ONUs for colorless upstream transmission, and the
      upstream and downstream signals are transmitted simultaneously over the same
      outer core for each ONU. By this means, the signals and local oscillators for
      upstream and downstream transmission all originate from the same laser which is
      located at OLT. With the help of the KK-based receiver, SSBI could be effectively
      eliminated and the fiber dispersion can also be digitally compensated due to the
      reconstruction of the complex field of the received signal. Moreover, by using
      single sideband Nyquist-shaped subcarrier modulation with 16-ary quadrature
      amplitude modulation (SSB-Nyquist-16QAM) technique, the upstream and downstream
      signals are allocated to occupy the left and right sideband of the optical
      carrier respectively, and thus the RB noise can be easily removed by a simple
      optical filter in the receiver. In our experiment, the carrier-to-signal power
      ratio (CSPR) and the frequency gap between the upstream and downstream signals
      are investigated. Furthermore, bidirectional transmission of 60 Gbps SSB-Nyquist
      16QAM signals over 50 km 7-core fiber are successfully achieved, and the
      frequency gap between the upstream and downstream signals is only 3 GHz.

PMID- 30114163
TI  - Polarization switching realized in the continuous-wave and acousto-optic Q
      switched pulse Er:Yb:LaMgB5O10 lasers at 1556 and 1568 nm.
AB  - By using the natural birefringence of crystalline quartz, the switching of a 1568
      nm laser with polarization parallel to the Z optical indicatrix axis to a 1556 nm
      laser with polarization parallel to the Y optical indicatrix axis was observed in
      both continuous-wave and acousto-optic Q-switched pulse lasers based on an X-cut
      Er:Yb:LaMgB5O10 crystal, when the alignment of the output mirror in a 976 nm
      diode-end-pumped plano-concave resonator was precisely tilted. For the continuous
      wave regime, a 1568 nm laser with a maximum output power of 500 mW and slope
      efficiency of 16%, as well as a 1556 nm laser with a maximum output power of 400
      mW and slope efficiency of 13.5% were realized, respectively. For the Q-switched
      regime, a 1568 nm pulse laser with an energy of 144 MUJ and width of 300 ns, as
      well as a 1556 nm pulse laser with an energy of 168 MUJ and width of 270 ns, were
      obtained respectively by precisely tilting the alignment of the output mirror,
      when the absorbed pump power was 4.0 W and pulse repetition frequency was 0.5
      kHz.

PMID- 30114164
TI  - Flexible and tunable terahertz all-dielectric metasurface composed of ceramic
      spheres embedded in ferroelectric/elastomer composite: erratum.
AB  - We report an error in our paper [Opt. Express 26, 11633 2018]. The SEM picture
      shown in Fig. 1(e)Fig. 1(a)-(d) The fabrication process of all-dielectric
      metasurface. (e) The scanning electron microscope (SEM) photograph of fabricated
      sample. was incorrect. This was due to an error during manuscript preparation:
      The SEM picture of control group is inadvertently provided in Fig. 1(e), instead
      of correct SEM picture of sample. Figures 1(a)-1(d) are correct and remain
      unchanged, and this error does not affect the results or conclusions of the
      paper. We apologize for any confusion this may have caused.

PMID- 30114165
TI  - Self-pulsing in single section ring lasers based on quantum dot materials: theory
      and simulations.
AB  - We studied theoretically coherent phenomena in the multimode dynamics of single
      section semiconductor ring lasers with quantum dots (QDs) active region. In the
      unidirectional ring configuration our simulations show the occurrence of self
      mode-locking in the system leading to ultra-short pulses (sub-picoseconds) with a
      terahertz repetition rate. As confirmed by the linear stability analysis (LSA) of
      the traveling wave (TW) solutions this phenomenon is triggered by an analogous of
      the Risken-Nummedal-Graham-Haken (RNGH) instability affecting the multimode
      dynamics of two-level lasers.

PMID- 30114166
TI  - Ultrabroadband etalon-free detection of infrared transients by van-der-Waals
      contacted sub-10-um GaSe detectors.
AB  - We demonstrate ultrabroadband electro-optic detection of multi-THz transients
      using mechanically exfoliated flakes of gallium selenide of a thickness of less
      than 10 um, contacted to a diamond substrate by van-der-Waals bonding. While the
      low crystal thickness allows for extremely broadband phase matching, the
      excellent optical contact with the index-matched substrate suppresses multiple
      optical reflections. The high quality of our structure makes our scheme suitable
      for the undistorted and artifact-free observation of electromagnetic waveforms
      covering the entire THz spectral range up to the near-infrared regime without the
      need for correction for the electro-optic response function. With the current
      revolution of chemically inert quasi-two-dimensional layered materials, we
      anticipate that exfoliated van-der-Waals materials on index-matched substrates
      will open new flexible ways of ultrabroadband electro-optic detection at
      unprecedented frequencies.

PMID- 30114167
TI  - Coherent X-ray source generation with off-resonance laser modulation.
AB  - The generation of ultrashort coherent radiation in the extreme-ultraviolet (EUV)
      and soft X-ray regimes is of great significance in a broad range of research. In
      this paper, a promising scheme for generating coherent harmonic radiation using
      off-resonance seed laser modulation is discussed. The off-resonance seed laser,
      whose wavelength differs from the resonant wavelength of the undulator, is first
      used to modulate the angular distribution of the electron beam (e beam) in the
      undulator (modulator). After passing through a dispersion section, strong
      coherent micro-bunching is introduced into the e beam, which contains high-order
      harmonic components of the seed laser. Theoretical analysis and simulations
      indicate that this method can be used for the generation of coherent EUV and soft
      X-ray radiation at sub-gigawatt power in a meter-scale undulator (radiator).

PMID- 30114168
TI  - Large-area single photon compressive imaging based on multiple micro-mirrors
      combination imaging method.
AB  - We demonstrate a single photon compressive imaging system with the image plane up
      to the entire digital micro-mirror device (DMD) work area. A parallel light
      source is designed to reduce the influence of light scattering on imaging
      resolution and a photon counting photomultiplier tube (PMT) with a large
      photosensitive area is used to effectively collect light reflected from the full
      screen of DMD. A control and counting circuit, based on Field-Programmable Gate
      Array (FPGA), is developed to load binary random matrix into the DMD controller
      for each measurement, and to count single-photon pulse output from PMT
      simultaneously. To reduce imaging time and huge memory occupation for image
      reconstruction, a multiple micro-mirrors combination imaging method is proposed.
      The signal-to-noise ratio and detection limit of the imaging system is
      theoretically deduced. Theoretical analysis and experimental results show that
      micro-mirrors combination imaging method is more suitable for faster imaging in a
      weaker-light-level environment. In order to achieve high imaging quality, the
      size of the combined pixels and the average time of each measurement should be
      moderate, so that the impact of Poisson shot noise is minimized.

PMID- 30114169
TI  - In-fiber Mach-Zehnder interferometer with piecewise interference spectrum based
      on hole-assisted dual-core fiber for refractive index sensing.
AB  - We demonstrate theoretically and experimentally a novel in-fiber Mach-Zehnder
      interferometer (MZI) with piecewise interference spectrum. The interferometer is
      constructed by splicing a short section of single eccentric hole-assisted dual
      core fiber (SEHADCF) to two single mode fibers (SMFs) with a lateral-offset. Due
      to the offset splicing and the small distance between cores, different core modes
      in two cores of the SEHADCF can be excited to form interference at the different
      wavelength ranges. The discontinuous region of the interference spectrum can be
      employed as a mark to identify the order of the interference valley. The in-fiber
      MZI is experimentally investigated as a refractive index sensor, the sensitivity
      of 353.9 nm/RIU is obtained in the RI range of 1.335 ~1.395. The in-fiber MZI
      with a high sensitivity has a great potential in biological and chemical
      applications. Especially, due to the ability to identify the order of
      interference valleys by the discontinuous region, the proposed in-fiber MZI can
      improve the reliability of fiber sensors in remote monitoring applications.

PMID- 30114171
TI  - Cavity optofluidics: a MUdroplet's whispering-gallery mode makes a MUvortex.
AB  - We experimentally demonstrate light-flow interaction, in which the angular
      momentum of circulating light excites micro-vortices. In contrast with the solid
      phase of matter, where one has to overcome static friction in order to start
      motion, liquids have no "static drag." Relevant to almost all optofluidic micro
      systems hence, MUWatt optical power is sufficient to start flows, even in liquids
      50 times more viscous than water. We map the flows to be three-dimensional (3D)
      by using a technique based on fluorescent nano-emitters; to reveal, as expected,
      flow speeds proportional to power divided by viscosity.

PMID- 30114170
TI  - Fidelity test for through-focus or volumetric type of optical imaging methods.
AB  - Rapid increase in interest and applications of through-focus (TF) or volumetric
      type of optical imaging in biology and other areas has resulted in the
      development of several TF image collection methods. Achieving quantitative
      results from images requires standardization and optimization of image
      acquisition protocols. Several standardization protocols are available for
      conventional optical microscopy where a best-focus image is used, but to date,
      rigorous testing protocols do not exist for TF optical imaging. In this paper, we
      present a method to determine the fidelity of the TF optical data using the TF
      scanning optical microscopy images.

PMID- 30114172
TI  - Dynamic control of the interference pattern of surface plasmon polaritons and its
      application to particle manipulation.
AB  - This study proposes a method of dynamically controlling the interference pattern
      of surface plasmon polaritons (SPPs) within a four-slit structure by changing the
      phase difference between multiple-incident Gaussian beams. The theoretical
      analysis of the controlling mechanism of the SPP interference field and the
      numerical simulation of the generation and movement of both one-dimensional and
      two-dimensional SPP interference fields are provided. In addition, through
      simulation, this study demonstrates using the controllable two-dimensional SPP
      interference bright spots field for manipulating particles in static liquids.

PMID- 30114173
TI  - New theoretical formulation for the determination of radiance transmittance at
      the water-air interface: comment.
AB  - We challenge a recent paper in this journal suggesting that the well-established
      formula governing the transmittance of radiance across a refracting interface
      needs revision [Optics Express, 25(22) 27086 (2017)]. We provide a simple example
      of radiative transfer across an interface showing that the accepted formula is
      correct.

PMID- 30114174
TI  - New theoretical formulation for the determination of radiance transmittance at
      the water-air interface: reply.
AB  - Gordon and Voss in their comment challenge the recently published paper [Opt.
      Express25, 27086 (2017)] on the unity factor of radiance transmittance of the
      assumed hypothetical case (i.e., for the albedo equal to 1) and question the
      dependence of particulate contribution to the refractive index of water. Here, we
      provide answers to their comments.

PMID- 30114175
TI  - High-power tunable mid-infrared fiber gas laser source by acetylene-filled hollow
      core fibers.
AB  - High-power tunable pulsed and CW mid-infrared fiber gas laser sources in
      acetylene-filled hollow-core fibers, to the best of our knowledge, are
      demonstrated for the first time. By precisely tuning the wavelength of the pump
      source, an amplified tunable 1.5 MUm diode laser, to match different absorption
      lines of acetylene, the laser output is step-tunable in the range of 3.09~3.21
      MUm with a maximum pulse average power of ~0.3 W (~0.6 MUJ pulse energy) and a
      maximum CW power of ~0.77 W, making this system the first watt-level tunable
      fiber gas laser operating at mid-infrared range. The output spectral and power
      characteristics are systemically studied, and the explanations about the change
      of the ratio of the P over R branch emission lines with the pump power and the
      gas pressure are given, which is useful for the investigations of mid-infrared
      fiber gas lasers.

PMID- 30114176
TI  - Omnidirectional beam steering using aperiodic optical phased array with high
      error margin.
AB  - We propose a pattern-search-like algorithm to design an aperiodic optical phased
      array for extensive applications in light detection and ranging and free-space
      communication. The designed phased array with 128 isotropic elements achieves a
      scan range, peak side-lobe level, minimum beam width, and mean pitch of +/- 82
      degrees , -14.34 dB, 0.062 degrees , and 9.75 MUm, respectively. To our
      knowledge, it has the widest steering range, narrowest divergence, and largest
      mean pitch for the same waveguide number. The minimum pitch can be greater than
      2.67lambda to avoid cross-coupling. The calculated relationship between the
      machine error and side-lobe level indicates that the designed structure has a
      higher error tolerance than its uniformly spaced counterpart.

PMID- 30114177
TI  - High-order mode Yb-doped fiber lasers based on mode-selective couplers.
AB  - We experimentally investigate high-order modes (HOMs) generating at the
      wavelength of 1.0 MUm in all-fiber Yb-doped lasers based on mode-selective
      couplers (MSCs). Broadband MSCs for HOMs conversion are achieved by optimizing
      the phase-matching condition at 1.0 MUm. Efficient generation of HOMs is
      demonstrated with the MSCs inserted both into continuous-wave and mode-locked
      fiber lasers. The slope efficiencies of HOMs (LP11, LP02 and LP21) are presented
      and discussed. Additionally, cylindrical vector and orbital angular momentum
      beams are produced out of the MSCs by controlling the polarization states. The
      results show proof-of-concept implementation of the MSCs, which enables high
      efficiency of HOMs generation especially in pulsed fiber lasers and holds
      promising applications in laser material processing.

PMID- 30114178
TI  - Controllable Gaussian-shaped soliton clusters in strongly nonlocal media.
AB  - In this paper, we discuss the evolution of the Gaussian-shaped soliton clusters
      in strongly nonlocal nonlinear media, which is modeled by the nonlinear
      Schrodinger equation. The influences of three initial incident parameters (the
      initial transverse velocity, the initial position, the input power) on
      propagation dynamics of the soliton clusters are all discussed in detail. The
      results show that the intensity distribution, the trajectory, the center
      distance, and the angular velocity of the clusters can be controlled by adjusting
      the initial incident parameters. A series of analytical solutions on the
      propagation dynamics of the clusters are derived by borrowing ideas from
      classical physics. The results in this paper may have potential applications in
      the beam controlling and all-optical interconnection with the interacting
      characteristics of (2+1)-dimensional soliton clusters.

PMID- 30114179
TI  - Free-space-based multiple-access frequency dissemination with optical frequency
      comb.
AB  - We demonstrate a free-space-based multiple-access frequency dissemination with an
      optical frequency comb by using a passive phase conjunction correction technique.
      Timing fluctuations and Allan Deviations are both measured to characterize the
      excess frequency instability incurred during the frequency transfer process. By
      reproducing a 2 GHz radio-frequency signal at a middle point over a 60-m long
      free-space link in 5000 s, the total root-mean-square (RMS) timing fluctuation
      was measured to be about 224 fs with a fractional frequency instability on the
      order of 8 * 10-14 at 1 s and 1 * 10-16 at 1000 s. This free-space-based multiple
      access frequency transfer with passive phase conjunction correction can be used
      to disseminate a stable frequency signal at an arbitrary point in a free-space
      link.

PMID- 30114181
TI  - Securing noise-adaptive selection of interference signal by nonlinear detection.
AB  - In an interferometer, the interference fringe signal is typically linearly
      detected and modulated to a specific frequency region. A nonlinear detector
      yields the interference fringes of the fundamental and high-harmonic waves in
      different frequency regions. We analyze the formation of nonlinearly detected
      interference fringes. We demonstrate, for the first time, that the interference
      fringes of high-harmonic waves can also be used to determine the position of zero
      optical path length difference between reference and object mirrors. This noise
      adaptive selectability of the interference fringe signal is guaranteed by the
      fact that the positions of the peak envelopes of the interference fringes for the
      fundamental and high-harmonic waves are matched at zero optical path length. The
      proposed method is verified using experimental data. This technique can be
      applied not only to surface profiling but also to length measurements.

PMID- 30114180
TI  - Fast generation of full analytical polygon-based computer-generated holograms.
AB  - A fast calculation method to obtain the full-analytical frequency spectrum of a
      spatial triangle based on the three-dimensional (3D) affine transformation is
      presented. Computer-generated holograms (CGHs) of an object can then be generated
      rapidly using the angular spectrum for propagation. The derivation process in the
      theory, which has more preciseness, indicates a difference from previous methods
      based on affine transformations ([Appl. Opt.47, 1567 (2008)Appl. Opt.52, A290
      (2013)]). The proposed method to achieve 3D transformation from an arbitrary
      triangle to a primitive triangle includes two steps: 3D rotation and 2D affine
      transformation. The overall transform matrix is given by the product of a
      rotation matrix and a 2D affine matrix. A modified back-face culling is also
      introduced based on exterior normal for correct occlusion relation. Several
      complex 3D objects are implemented successfully using the proposed method in
      numerical simulations and optical experiments. The resulting computation time
      demonstrates that the efficiency of the proposed method is enhanced as compared
      to that of previous works.

PMID- 30114182
TI  - Discrete temporal Talbot effect in synthetic mesh lattices.
AB  - We investigate the discrete temporal Talbot effect in a synthetic mesh lattice by
      employing two coupled fiber loops with different lengths. The lattice consists of
      the round-trip number and time delay of pulse trains propagating in the fiber
      loops. The Talbot effect occurs only as the incident pulse train in one loop has
      a temporal period that is 1, 2, or 4 folds of time interval corresponding to the
      length difference of the two loops. By varying the splitting ratio of coupler
      connecting the two loops, the lattice band structure can be engineered and so do
      the Talbot distance, which can be further tuned by imposing an initial linear
      phase distribution on the incident pulse train. In addition, the incident periods
      for Talbot effect can also be fractional fold by using time multiplexing. The
      study may find applications in temporal cloaking, passive amplifying, and pulse
      repetition rate multiplication.

PMID- 30114183
TI  - Reciprocity approach for calculating the Purcell effect for emission into an open
      optical system.
AB  - Based on the reciprocity theorem, we present a formalism to calculate the power
      emitted by a dipole source into a particular propagating mode leaving an open
      optical system. The open system is completely arbitrary and the approach can be
      used in analytical calculations but may also be combined with numerical
      electromagnetic solvers to describe the emission of light sources into complex
      systems. We exemplify the use of the formalism in numerical simulations by
      analyzing the emission of a dipole that is placed inside a cavity with connected
      single mode exit waveguide. Additionally, we show at the example of a practical
      ring resonator system how the approach can be applied to systems that offer
      multiple electromagnetic energy decay channels. As a consequence of its inherent
      simplicity and broad applicability, the approach may serve as a powerful and
      practical tool for engineering light-matter-interaction in a variety of active
      optical systems.

PMID- 30114184
TI  - Laser-based white-light source for high-speed underwater wireless optical
      communication and high-efficiency underwater solid-state lighting.
AB  - White light generated by mixing the red, green, and blue laser diodes (RGB LDs)
      for simultaneous high-speed underwater wireless optical communication (UWOC) and
      high-efficiency underwater solid-state lighting (SSL) was proposed and
      demonstrated experimentally for the first time. The allowable maximum real-time
      data transmission rates of 3.2 Gbps, 3.4 Gbps, and 3.1 Gbps for RGB LDs with
      corresponding BERs of 3.6 * 10-3, 3.5 * 10-3 and 3.7 * 10-3 were obtained at a
      2.3 m underwater transmission distance using an on-off keying (OOK) modulation
      scheme, respectively. And the corresponding UWOC aggregate data rate of 9.7 Gbps
      was achieved based on RGB LDs-based wavelength-division multiplexing (WDM) UWOC.
      Moreover, UWOC and underwater SSL by using RGB LDs mixed white light were
      investigated at different scenarios over an underwater link of 2.3 m. The RGB LDs
      mixed white light-based UWOC system without optical diffusers yielded a maximum
      allowable data rate of 8.7 Gbps with Commission International de l'Eclairage
      coordinates (CIE) of (0.3154, 0.3354), a correlated color temperature of 6322 K,
      a color rendering index of 69.3 and a corresponding illuminance of 7084 lux.
      Furthermore, optical diffusers were employed to provide large-area underwater
      SSL. The LDs mixed white light-based UWOC system with line and circle optical
      diffusers implemented data rates of 5.9 Gbps and 6.6 Gbps with CIE coordinates of
      (0.3183, 0.3269) and (0.3298, 0.3390), respectively. This work suggests the
      potential of LDs for applications in high-efficiency underwater white-light SSL
      and high-speed UWOC.

PMID- 30114185
TI  - Chiroptical response of a single plasmonic nanohelix.
AB  - We investigate the chiroptical response of a single plasmonic nanohelix
      interacting with a weakly focused circularly polarized Gaussian beam. The optical
      scattering at the fundamental resonance is characterized experimentally and
      numerically. The angularly resolved scattering of the excited nanohelix is
      verified experimentally and it validates the numerical results. We employ a
      multipole decomposition analysis to study the fundamental and first higher-order
      resonance of the nanohelix, explaining their chiral properties in terms of the
      formation of chiral dipoles.

PMID- 30114186
TI  - MimicrEE2: Genome-wide forward simulations of Evolve and Resequencing studies.
AB  - Evolve and Resequencing (E&R) studies allow us to monitor adaptation at the
      genomic level. By sequencing evolving populations at regular time intervals, E&R
      studies promise to shed light on some of the major open questions in evolutionary
      biology such as the repeatability of evolution and the molecular basis of
      adaptation. However, data interpretation, statistical analysis and the
      experimental design of E&R studies increasingly require simulations of evolving
      populations, a task that is difficult to accomplish with existing tools, which
      may i) be too slow, ii) require substantial reformatting of data, iii) not
      support an adaptive scenario of interest or iv) not sufficiently capture the
      biology of the used model organism. Therefore we developed MimicrEE2, a multi
      threaded Java program for genome-wide forward simulations of evolving
      populations. MimicrEE2 enables the convenient usage of available genomic
      resources, supports biological particulars of model organism frequently used in
      E&R studies and offers a wide range of different adaptive models (selective
      sweeps, polygenic adaptation, epistasis). Due to its user-friendly and efficient
      design MimicrEE2 will facilitate simulations of E&R studies even for small labs
      with limited bioinformatics expertise or computational resources. Additionally,
      the scripts provided for executing MimicrEE2 on a computer cluster permit the
      coverage even of a large parameter space. MimicrEE2 runs on any computer with
      Java installed. It is distributed under the GPLv3 license at
      https://sourceforge.net/projects/mimicree2/.

PMID- 30114188
TI  - Lactosylceramide synthases encoded by B4galt5 and 6 genes are pivotal for
      neuronal generation and myelin formation in mice.
AB  - It is uncertain which beta4-galactosyltransferase (beta4GalT; gene name, B4galt),
      beta4GalT-5 and/or beta4GalT-6, is responsible for the production of
      lactosylceramide (LacCer) synthase, which functions in the initial step of
      ganglioside biosynthesis. Here, we generated conditional B4galt5 knockout
      (B4galt5 cKO) mice, using Nestin-Cre mice, and crossed these with B4galt6 KO mice
      to generate B4galt5 and 6 double KO (DKO) mice in the central nervous system
      (CNS). LacCer synthase activity and major brain gangliosides were completely
      absent in brain homogenates from the DKO mice, although LacCer synthase activity
      was about half its normal level in B4galt5 cKO mice and B4galt6 KO mice. The DKO
      mice were born normally but they showed growth retardation and motor deficits at
      2 weeks and died by 4 weeks of age. Histological analyses showed that myelin
      associated proteins were rarely found localized in axons in the cerebral cortex,
      and axonal and myelin formation were remarkably impaired in the spinal cords of
      the DKO mice. Neuronal cells, differentiated from neurospheres that were prepared
      from the DKO mice, showed impairments in neurite outgrowth and branch formation,
      which can be explained by the fact that neurospheres from DKO mice could weakly
      interact with laminin due to lack of gangliosides, such as GM1a. Furthermore, the
      neurons were immature and perineuronal nets (PNNs) were poorly formed in DKO
      cerebral cortices. Our results indicate that LacCer synthase is encoded by
      B4galt5 and 6 genes in the CNS, and that gangliosides are indispensable for
      neuronal maturation, PNN formation, and axonal and myelin formation.

PMID- 30114187
TI  - The last universal common ancestor between ancient Earth chemistry and the onset
      of genetics.
AB  - All known life forms trace back to a last universal common ancestor (LUCA) that
      witnessed the onset of Darwinian evolution. One can ask questions about LUCA in
      various ways, the most common way being to look for traits that are common to all
      cells, like ribosomes or the genetic code. With the availability of genomes, we
      can, however, also ask what genes are ancient by virtue of their phylogeny rather
      than by virtue of being universal. That approach, undertaken recently, leads to a
      different view of LUCA than we have had in the past, one that fits well with the
      harsh geochemical setting of early Earth and resembles the biology of prokaryotes
      that today inhabit the Earth's crust.

PMID- 30114191
TI  - Genetic trends and trade-offs between growth and reproductive traits in a Nellore
      herd.
AB  - The knowledge of genetic trends and trade-offs between growth and reproductive
      traits might be useful to understand the evolution of these traits in livestock
      and natural populations of animals. We estimated the genetic trends and trade
      offs between pre-weaning growth and calving intervals of Nellore animals from a
      commercial farm. Two-trait animal models were used to estimate covariance
      components and breeding values (EBV) for direct and maternal genetic effects of
      pre-weaning growth and direct genetic effects of calving intervals. Regression
      analyses were performed to examine the relationship between direct and maternal
      EBV of pre-weaning growth and direct EBV of calving intervals (dependent
      variables) and the coefficient of generation of each animal (independent
      variable). We also performed regression analyses to examine the relationship
      between direct EBV of calving intervals (dependent variables) and direct and
      maternal EBV of pre-weaning growth (independent variables). The genetic trends
      for direct and maternal genetic effect for pre-weaning growth were significant
      and presented genetic evolution in the studied Nellore herd. The genetic trends
      for the reproductive traits were also significant but indicated genetic changes
      in an unfavorable way. The genetic correlations between direct effects of pre
      weaning growth and calving intervals traits and the genetic correlations between
      maternal effects of pre-weaning growth traits and direct effects of calving
      interval traits were not different from zero. The presence of trade-offs between
      the direct effects of growth and reproductive traits were confirmed through
      regression from direct EBV of calving intervals over EBV of pre-weaning growth
      traits. In addition, regression analyses showed that selection to increase pre
      weaning growth also increased calving intervals. Our results showed that pre
      weaning growth and calving intervals are increasing over generations and that
      trade-offs occurred between those traits in the studied Nellore herd.

PMID- 30114189
TI  - AAV9-mediated telomerase activation does not accelerate tumorigenesis in the
      context of oncogenic K-Ras-induced lung cancer.
AB  - Short and dysfunctional telomeres are sufficient to induce a persistent DNA
      damage response at chromosome ends, which leads to the induction of senescence
      and/or apoptosis and to various age-related conditions, including a group of
      diseases known as "telomere syndromes", which are provoked by extremely short
      telomeres owing to germline mutations in telomere genes. This opens the
      possibility of using telomerase activation as a potential therapeutic strategy to
      rescue short telomeres both in telomere syndromes and in age-related diseases, in
      this manner maintaining tissue homeostasis and ameliorating these diseases. In
      the past, we generated adeno-associated viral vectors carrying the telomerase
      gene (AAV9-Tert) and shown their therapeutic efficacy in mouse models of cardiac
      infarct, aplastic anemia, and pulmonary fibrosis. Although we did not observe
      increased cancer incidence as a consequence of Tert overexpression in any of
      those models, here we set to test the safety of AAV9-mediated Tert overexpression
      in the context of a cancer prone mouse model, owing to expression of oncogenic K
      ras. As control, we also treated mice with AAV9 vectors carrying a catalytically
      inactive form of Tert, known to inhibit endogenous telomerase activity. We found
      that overexpression of Tert does not accelerate the onset or progression of lung
      carcinomas, even when in the setting of a p53-null background. These findings
      indicate that telomerase activation by using AAV9-mediated Tert gene therapy has
      no detectable cancer-prone effects in the context of oncogene-induced mouse
      tumors.

PMID- 30114190
TI  - Early metabolic 18F-FDG PET/CT response of locally advanced squamous-cell
      carcinoma of head and neck to induction chemotherapy: A prospective pilot study.
AB  - OBJECTIVE: The objective of this study was to assess the clinical value of 18
      fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG
      PET/CT) after the first cycle of induction chemotherapy (IC) in locally advanced
      squamous cell carcinoma of the head and neck (LASCCHN). METHODS AND FINDINGS: A
      prospective, single-arm, single center study was performed, with patients
      enrolled between February 2010 and July 2013.Patients (n = 49) with stage III/IVA
      B LASCCHN who underwent IC with taxanes, cisplatin, and fluorouracil were
      recruited. Staging procedures included loco-regional and chest imaging,
      endoscopic examination, and PET/CT scan. On day 14 of the first cycle, a second
      PET/CT scan was performed. Patients with no early increase in regional lymph node
      maximum 18F-FDG standard uptake value (SUV), detected using 18F-FDG PET/CT after
      first IC had better progression-free survival (hazard ratio (HR) = 0.18, 95%,
      confidence interval (CI) 0.056-0.585; p = 0.004) and overall survival (HR = 0.14,
      95% CI 0.040-0.498; p = 0.002), and were considered responders. In this subgroup,
      patients who achieved a reduction of >= 45% maximum primary tumor SUV experienced
      improved progression-free (HR = 0.23, 95% CI 0.062-0.854; p = 0.028) and overall
      (HR = 0.11, 95% CI 0.013-0.96; p = 0.046) survival. CONCLUSIONS: These results
      suggest a potential role for early response evaluation with PET/CT examination in
      patients with LASCCHN undergoing IC. Increased regional lymph node maximum SUV
      and insufficient decrease in primary tumor uptake predict poorer outcomes.

PMID- 30114193
TI  - Access to medicines for acute illness and antibiotic use in residents: A
      medicines household survey in Sichuan Province, western China.
AB  - OBJECTIVE: To investigate medicine accessibility and antibiotic use in households
      in western China using World Health Organization (WHO) methodology as well as to
      identify the influencing factor of care-seeking outside the home and primary
      determinant factors that influence the use of antibiotics in Chinese residents.
      METHODS: A cross-sectional household survey was conducted from March to July
      2015, and 1200 households from six cities in Sichuan China were selected for a
      questionnaire survey using stratified multistage random cluster sampling. We used
      logistic regression models to identify the determinants of care-seeking outside
      the home and subsequent antibiotic use among the surveyed residents. RESULTS:
      Overall, 1103 valid questionnaires were collected, and 458 households reported
      that they had had experienced at least one acute illness in the previous 2 weeks.
      Of these households, 97.2% of individuals with acute conditions sought care
      outside their homes and 40.1% of individuals who took medicine received
      antibiotics. Only 15.9% of the individuals with acute conditions reported that
      the medical insurance reimbursement covered at least one medicine. According to
      the multivariate analyses, women were less likely to seek care outside the home
      compared to men. Among those who sought outside care, fever and upper respiratory
      symptoms increased the odds of taking antibiotics, and visiting a private
      hospital also increased antibiotic use. Low-income households were less likely to
      receive antibiotics. Symptoms were strong determinants of antibiotic use when
      patients sought outside care. CONCLUSION: The accessibility of medicine for acute
      illness among households in western China was favorable; however, medical
      insurance reimbursement must be improved. The nature of the symptoms and patterns
      of care-seeking had the greatest influence on the decision to take antibiotics
      among residents with acute conditions. The percentage of antibiotic use in
      patients with acute illness has declined, but the indications for using
      antibiotics must be standardized.

PMID- 30114192
TI  - On the internal reaction forces, energy absorption, and fracture in the hip
      during simulated sideways fall impact.
AB  - The majority of hip fractures have been reported to occur as a result of a fall
      with impact to the greater trochanter of the femur. Recently, we developed a
      novel cadaveric pendulum-based hip impact model and tested two cadaveric femur
      pelvis constructs, embedded in a soft tissue surrogate. The outcome was a femoral
      neck fracture in a male specimen while a female specimen had no fracture. The aim
      of the present study was, first, to develop a methodology for constructing and
      assessing the accuracy of explicit Finite Element Models (FEMs) for simulation of
      sideways falls to the hip based on the experimental model. Second, to use the
      FEMs for quantifying the internal reaction forces and energy absorption in the
      hip during impact. Third, to assess the potential of the FEMs in terms of
      separating a femoral fracture endpoint from a non-fracture endpoint. Using a non
      linear, strain rate dependent, and heterogeneous material mapping strategy for
      bone tissue in these models, we found the FEM-derived results to closely match
      the experimental test results in terms of impact forces and displacements of
      pelvic video markers up to the time of peak impact force with errors below 10%.
      We found the internal reaction forces in the femoral neck on the impact side to
      be approximately 35% lower than the impact force measured between soft tissue and
      ground for both specimens. In addition, we found the soft tissue to be the
      component that absorbed the largest part of the energy of the tissue types in the
      hip region. Finally, we found surface strain patterns derived from FEM results to
      match the fracture location and extent based on post testing x-rays of the
      specimens. This is the first study with quantitative data on the energy
      absorption in the pelvic region during a sideways fall.

PMID- 30114194
TI  - When taxonomy and biological control researchers unite: Species delimitation of
      Eadya parasitoids (Braconidae) and consequences for classical biological control
      of invasive paropsine pests of Eucalyptus.
AB  - The invasive eucalyptus tortoise beetle, Paropsis charybdis, defoliates
      plantations of Eucalyptus nitens in New Zealand. Recent efforts to identify host
      specific biological control agents (parasitoids) from Tasmania, Australia, have
      focused on the larval parasitoid wasp, Eadya paropsidis (Braconidae), first
      described in 1978. In Tasmania, Eadya has been reared from Paropsisterna agricola
      (genus abbreviated Pst.), a smaller paropsine that feeds as a larva on juvenile
      rather than adult foliage of Eucalyptus nitens. To determine which of the many
      paropsine beetle hosts native to Tasmania are utilized by E. paropsidis, and to
      rule out the presence of cryptic species, a molecular phylogenetic approach was
      combined with host data from rearing experiments from multiple locations across
      six years. Sampling included 188 wasps and 94 beetles for molecular data alone.
      Two mitochondrial genes (COI and Cytb) and one nuclear gene (28S) were analyzed
      to assess the species limits in the parasitoid wasps. The mitochondrial genes
      were congruent in delimiting four separate phylogenetic species, all supported by
      morphological examinations of Eadya specimens collected throughout Tasmania.
      Eadya paropsidis was true to the type description, and was almost exclusively
      associated with P. tasmanica. A new cryptic species similar to E. paropsidis,
      Eadya sp. 3, was readily reared from Pst. agricola and P. charybdis from all
      sites and all years. Eadya sp. 3 represents the best candidate for biological
      control of P. charybdis and was determined as the species undergoing host range
      testing in New Zealand for its potential as a biological control agent. Another
      new species, Eadya sp. 1, was morphologically distinctive and attacked multiple
      hosts. The most common host was Pst. variicollis, but was also reared from Pst.
      nobilitata and Pst. selmani. Eadya sp. 1 may have potential for control against
      Pst. variicollis, a new incursion in New Zealand, and possibly Pst. selmani in
      Ireland. Our molecular data suggests that Pst. variicollis is in need of
      taxonomic revision and the geographic source of the beetle in New Zealand may not
      be Tasmania. Eadya sp. 2 was rarely collected and attacked P. aegrota elliotti
      and P. charybdis. Most species of Eadya present in Tasmania are not host specific
      to one beetle species alone, but demonstrate some host plasticity across the
      genera Paropsisterna and Paropsis. This study is an excellent example of
      collaborative phylogenetic and biological control research prior to the release
      of prospective biological control agents, and has important implications for the
      Eucalyptus industry worldwide.

PMID- 30114195
TI  - Influence of age, BMI and parity on the success rate of midurethral slings for
      stress urinary incontinence.
AB  - AIMS: Our aim was to evaluate, in a second data analysis of the prospective
      randomized controlled trial conducted by Austrian Urogynaecology Working Group,
      the effect of age, BMI and parity at the time of surgery on short- and long-term
      outcomes of women primarily treated for SUI (stress urinary incontinence) with
      midurethral slings. METHODS: In the original study 554 patients received randomly
      a retropubic (TVT) or a transobturator midurethral (TVT-O) sling procedure. 480
      (87%) and 277 (50%) patients were available for a follow-up efficacy evaluation
      at 3 months and 5 years respectively. RESULTS: Higher age and BMI at surgery
      appear to lead to a larger probability to have a positive stress test 5 years
      after surgery, but not after 3 months. Older patients seem to have a worse
      perception of improvement 5 years after surgery as compared to younger ones, as
      described by the PGI-I score. Age and BMI do not affect significantly the quality
      of life of women surgically treated for SUI, as reflected by the results of
      King's Health Questionnaire. Parity does not seem to have any effect on objective
      and subjective surgical outcomes. CONCLUSIONS: Higher age and BMI at surgery have
      a detrimental influence on the objective cure rate at 5 years after midurethral
      sling surgery; higher age also has a negative influence on subjective long-term
      outcomes. However, these demographic parameters do not influence significantly
      the quality of life of patients after anti-incontinence surgery. Parity does not
      show any significant influence on success rate of midurethral sling.

PMID- 30114196
TI  - Body composition analysis, anthropometric indices and lipid profile markers as
      predictors for prediabetes.
AB  - OBJECTIVES: To compare different anthropometric indices, Body composition
      analysis and lipid profile markers in terms of their ability to predict
      prediabetes (PD). METHODS: We enrolled 83 subjects with PD and 84 normoglycemic
      subjects who were matched for age and gender. The diagnosis of prediabetes was
      done according to the American Diabetes Association (ADA) criteria. All subjects
      were aged between 30-55 years of age and visited the outpatient department of
      tertiary care hospital. Anthropometric and lipid profile measurements were
      obtained. Analysis of body composition was done using Bodystat 1500MDD
      Instrument. Backward logistic regression was performed for detecting the
      predictors of PD. A receiver operator characteristic curve (ROC) with area under
      curve (AUC) was utilized for the accuracy of the predictors of PD. RESULTS:
      Comparison of anthropometric measurement and body composition analysis parameters
      between the two groups showed that Waist circumference (WC), Body mass index,
      Body Fat% were significantly higher whereas Extracellular water and Dry lean
      weight in percentage (ECW% and DLW%) were found to be lower in PD (p< 0.05).
      Higher triglyceride (TG) levels and lower high-density cholesterol (HDL-C) with
      high TG/HDL-C were seen in subjects with PD. Backward logistic regression
      analysis found the combination of Body Fat % with WC, TG, ECW% and DLW% as strong
      predictors of PD. In ROC analysis, ECW% (AUC = 0.703) was the most predictive
      measure, followed by WC (AUC = 0.702). CONCLUSION: This study demonstrated that
      estimation of Body Fat % combined with waist circumference, Extracellular water
      and Dry lean weight in percentage are valuable in screening and diagnosis of
      prediabetes. Plasma levels of TG in lipid profile measurements can also serve as
      an additional marker for prediction of prediabetes.

PMID- 30114197
TI  - How much does direct transmission between pigs contribute to Japanese
      Encephalitis virus circulation? A modelling approach in Cambodia.
AB  - Japanese Encephalitis (JE) is the most important cause of human encephalitis
      throughout Asia and the Pacific. Although JE is a vector-borne disease, it has
      been demonstrated experimentally that transmission between pigs can occur through
      direct contact. Whether pig-to-pig transmission plays a role in the natural
      epidemiological cycle of JE remains unknown. To assess whether direct
      transmission between pigs may occur under field conditions, we built two
      mathematical models of JE transmission incorporating vector-borne transmission
      alone or a combination of vector-borne and direct transmission. We used Markov
      Chain Monte Carlo (MCMC) techniques to estimate the parameters of the models. We
      fitted the models to (i) two serological datasets collected longitudinally from
      two pig cohorts (C1 and C2) during two periods of four months on a farm on the
      outskirts of Phnom-Penh, Cambodia and to (ii) a cross-sectional (CS) serological
      survey dataset collected from 505 swine coming from eight different provinces of
      Cambodia. In both cases, the model incorporating both vector-borne and direct
      transmission better explained the data. We computed the value of the basic
      reproduction number R0 (2.93 for C1, 2.66 for C2 and 2.27 for CS), as well as the
      vector-borne reproduction number Rpv and the direct transmission reproduction
      number Rpp. We then determined the contribution of direct transmission on R0
      (11.90% for C1, 11.62% for C2 and 7.51% for CS). According to our results, the
      existence of pig-to-pig transmission is consistent with our swine serological
      data. Thus, direct transmission may contribute to the epidemiological cycle of JE
      in Cambodia. These results need to be confirmed in other eco-climatic settings,
      in particular in temperate areas where pig-to-pig transmission may facilitate the
      persistence of JE virus (JEV) during cold seasons when there are no or few
      mosquitoes.

PMID- 30114198
TI  - Leaky resistance and the conditions for the existence of lytic bacteriophage.
AB  - In experimental cultures, when bacteria are mixed with lytic (virulent)
      bacteriophage, bacterial cells resistant to the phage commonly emerge and become
      the dominant population of bacteria. Following the ascent of resistant mutants,
      the densities of bacteria in these simple communities become limited by resources
      rather than the phage. Despite the evolution of resistant hosts, upon which the
      phage cannot replicate, the lytic phage population is most commonly maintained in
      an apparently stable state with the resistant bacteria. Several mechanisms have
      been put forward to account for this result. Here we report the results of
      population dynamic/evolution experiments with a virulent mutant of phage Lambda,
      lambdaVIR, and Escherichia coli in serial transfer cultures. We show that,
      following the ascent of lambdaVIR-resistant bacteria, lambdaVIR is maintained in
      the majority of cases in maltose-limited minimal media and in all cases in
      nutrient-rich broth. Using mathematical models and experiments, we show that the
      dominant mechanism responsible for maintenance of lambdaVIR in these resource
      limited populations dominated by resistant E. coli is a high rate of either
      phenotypic or genetic transition from resistance to susceptibility-a hitherto
      undemonstrated mechanism we term "leaky resistance." We discuss the implications
      of leaky resistance to our understanding of the conditions for the maintenance of
      phage in populations of bacteria-their "existence conditions."

PMID- 30114199
TI  - Risk of childhood cerebral palsy following prenatal exposure to beta2-adrenergic
      receptor agonist: A nationwide cohort study.
AB  - BACKGROUND: Cerebral palsy (CP) is the most common physical developmental
      disability in childhood with a prevalence of 2 to 3 per 1000 live births. beta2
      adrenoreceptor agonist (beta2AA) are widely used for the treatment of asthma.
      Maternal use of beta2AAs may increase the risk of adverse neuro-psychiatric
      health outcomes in the offspring. No study, however, has evaluated the effect of
      prenatal exposure to beta2AAs on the risk of CP. OBJECTIVE: To examine the
      association between prenatal exposure to beta2AAs and the risk of childhood
      cerebral palsy. METHODS: This population-based cohort study included all live
      singleton births in Denmark from January 1, 1997 to December 31, 2003. The
      information on outpatient prescriptions of beta2AAs was extracted from Danish
      National Prescription Registry. Children born to mothers who used beta2AAs from
      30 days before pregnancy until delivery were categorized as the exposed. To
      differentiate the effect of beta2AAs from the underlying indications, the
      exposure window was further extended to 2 years before pregnancy and the exposed
      groups were re-defined to represent different periods of exposure to maternal use
      of beta2AAs (use only before pregnancy, use only during pregnancy, and use both
      before and during pregnancy). Cases of CP were identified from the Danish
      Cerebral Palsy Register. Logistic regression was used to estimate incidence odds
      ratio (OR) of CP. RESULTS: Among all the 442,278 singletons, 19,616 (4.44%) were
      exposed to beta2AAs in utero (from 30 days before pregnancy until delivery). The
      risk of childhood CP was 0.21% in exposed and 0.19% in unexposed group, yielding
      an adjusted OR (aOR) 1.12 (95% confidence interval (CI): 0.82, 1.53). When
      extending the exposure time window to 2 years prior to pregnancy, no overall
      significant association was observed regardless of the exposure period. However,
      an increased risk of CP (aOR = 1.41, 95%CI: 0.92, 2.18) for maternal beta2AAs use
      during pregnancy was observed in female offspring, especially in those born at
      term (aOR = 1.65, 95%CI: 1.02, 2.67). This increase was mainly attributed to an
      increased risk in those born to mothers who used beta2AAs both before and during
      pregnancy (aOR = 1.81, 95%CI: 0.99, 3.33). CONCLUSIONS: We observed an
      association between maternal beta2AAs use during pregnancy and an increased risk
      of CP in female offspring, but we could not rule out confounding by the
      underlying indications for beta2AAs.

PMID- 30114200
TI  - Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia,
      characterised by large lymphoid aggregates and high inflammation.
AB  - OBJECTIVE: To determine whether the expression of IL17A and CD21L genes in
      inflamed rheumatoid synovia is associated with the neogenesis of ectopic lymphoid
      follicle-like structures (ELS), and if this aids the stratification of rheumatoid
      inflammation and thereby distinguishes patients with rheumatoid arthritis that
      might be responsive to specific targeted biologic therapies. METHODS: Expression
      of IL17A and CD21L genes was assessed by RT-PCR, qRT-PCR and dPCR in synovia from
      54 patients with rheumatoid arthritis. A subset of synovia (n = 30) was assessed
      by immunohistology for the presence of CD20+ B-lymphocytes and size of CD20+ B
      lymphocyte aggregates as indicated by maximum radial cell count. The molecular
      profiles of six IL17A+/CD21L+ and six IL17A-/CD21L- synovia were determined by
      complementary DNA microarray analysis. RESULTS: By RT-PCR, 26% of synovia
      expressed IL17A and 52% expressed CD21L. This provided the basis for
      distinguishing four subgroups of rheumatoid synovia: IL17A+/CD21L+ (18.5% of
      synovia), IL17A+/CD21L- (7.5%), IL17A-/CD21L+ (33.3%) and IL17A-/CD21L- (40.7%).
      While the subgroups did not predict clinical outcome measures, comparisons
      between the synovial subgroups revealed the IL17A+/CD21L+ subgroup had
      significantly larger CD20+ B-lymphocyte aggregates (P = 0.007) and a gene
      expression profile skewed toward B-cell- and antibody-mediated immunity. In
      contrast, genes associated with bone and cartilage remodelling were prominent in
      IL17A-/CD21L- synovia. CONCLUSIONS: Rheumatoid synovia can be subdivided on the
      basis of IL17A and CD21L gene expression. Ensuing molecular subgroups do not
      predict clinical outcome for patients but highlight high inflammation and the
      predominance of B-lymphocyte mediated mechanisms operating in IL17A+/CD21L+
      synovia. This may provide a rationale for more refined therapeutic selection due
      to the distinct molecular profiles associated with IL17A+/CD21L+ and IL17A-/CD21L
      rheumatoid synovia.

PMID- 30114201
TI  - Strong correlation of lumefantrine concentrations in capillary and venous plasma
      from malaria patients.
AB  - BACKGROUND: Lumefantrine is a long-acting antimalarial drug with an elimination
      half-life of over 3 days and protein binding of 99 percent. Correlation of
      lumefantrine concentrations from capillary plasma via fingerprick (Cc) versus
      venous plasma (Cv) remains to be defined. METHODS: Venous and capillary plasma
      samples were collected simultaneously from children, pregnant women, and non
      pregnant adults at 2, 24, 120hr post last dose of a standard 3-day artemether
      lumefantrine regimen they received for uncomplicated malaria. Some of the
      enrolled children and pregnant women were also HIV-infected. Samples were
      analyzed via liquid chromatography tandem mass spectrometry. Linear regression
      analysis was performed using the program Stata(r) SE12.1. RESULTS: In children,
      the linear regression equations for Cc vs Cv at 2, 24, and 120hr (day 7) post
      dose are [Cc] = 1.05*[Cv]+95.0 (n = 142, R2 = 0.977), [Cc] = 0.995*[Cv]+56.7 (n =
      147, R2 = 0.990) and [Cc] = 0.958*[Cv]+18.6 (n = 139, R2 = 0.994), respectively.
      For pregnant women, the equations are [Cc] = 1.04*[Cv]+68.1 (n = 43, R2 = 0.990),
      [Cc] = 0.997*[Cv]+37.3 (n = 43, R2 = 0.993) and [Cc] = 0.941*[Cv]+11.1 (n = 41,
      R2 = 0.941), respectively. For non-pregnant adults, the equations are [Cc] =
      1.05*[Cv]-117 (n = 32, R2 = 0.958), [Cc] = 0.962*[Cv]+9.21 (n = 32, R2 = 0.964)
      and [Cc] = 1.04*[Cv]-40.1 (n = 32, R2 = 0.988), respectively. In summary, a
      linear relationship with a slope of ~1 was found for capillary and venous
      lumefantrine levels in children, pregnant women and non-pregnant adults at 2hr,
      24hr and 120hr post last dose, representing absorption, distribution, and
      elimination phases. CONCLUSIONS: Capillary and venous plasma concentration of
      lumefantrine can be used interchangeably at 1:1 ratio. Capillary sampling method
      via finger prick is a suitable alternative for sample collection in clinical
      studies.

PMID- 30114202
TI  - Identifying shape transformations from photographs of real objects.
AB  - An important task of human visual cognition is to make inferences about
      properties of objects. One such property is an object's causal history: what
      happened to the object in its past (e.g., "this paper has been folded"). There is
      relatively little research on whether and how we make such inferences. We took
      photographs of objects from six different materials ('wax', 'aluminum foil',
      'gold foil', 'chicken wire', 'putty', 'cardboard') transformed by one of four
      shape-altering transformations ('folded', 'bent', 'crumpled', 'twisted'). By
      varying execution of transformation and viewpoint, we obtained 30 images of each
      material/transformation combination (720 images). We asked different groups of
      participants to: (1) name transformations and materials, (2) rate images with
      respect to the extent they belonged to each transformation or material class, and
      (3) classify images into the four transformation classes. Our results show that
      participants can infer transformations from object shape-with accuracy being
      modulated by object material. This inference of causal history from observed
      object shape shows that we can distinguish between intrinsic (material) and
      extrinsic (transformation) properties of the object. The separation of observed
      shape features by their causal origin ('shape scission') presumably involves both
      perceptual and cognitive abilities.

PMID- 30114203
TI  - The prehospital quick SOFA score is associated with in-hospital mortality in
      noninfected patients: A retrospective, cross-sectional study.
AB  - This study aimed to determine the accuracy of the quick Sequential Organ Failure
      Assessment (qSOFA) score in predicting mortality among prehospital patients with
      and without infection. This single-center, retrospective, cross-sectional study
      was conducted among patients who arrived via the emergency medical services
      (EMS). We calculated the qSOFA score and Modified Early Warning Score (MEWS) from
      prehospital records. We identified patients as infected if they received
      intravenous antibiotics at the emergency department or within the first 24 hours.
      Receiver operating characteristic analysis was used to evaluate and compare the
      performance of the qSOFA score, each physiological parameter, and the MEWS in
      predicting admission and in-hospital mortality in patients with and without
      infection. Multivariate analysis was used to evaluate the qSOFA score and other
      risk factors. Out of 1574 prehospital patients, 47.1% were admitted and 3.2% died
      in the hospital. The performance of the qSOFA score in predicting in-hospital
      mortality in noninfected patients was 0.70, higher than for each parameter and
      the MEWS. The areas under the curve for the qSOFA+ model vs. the qSOFA- model was
      0.77 vs. 0.68 for noninfected patients (p <0.05) and 0.71 vs. 0.68 for infected
      patients (p = 0.41). The likelihood ratio test comparing the qSOFA- and qSOFA+
      groups demonstrated significant improvement for noninfected patients (p <0.01).
      Multivariate regression analysis for in-hospital mortality demonstrated that the
      qSOFA score is an independent prognosticator for in-hospital mortality,
      especially among noninfected patients (odds ratio, 3.60; p <0.01). In conclusion,
      the prehospital qSOFA score was associated with in-hospital mortality in
      noninfected patients and may be a beneficial tool for identifying deteriorating
      patients in the prehospital setting.

PMID- 30114204
TI  - High glucose and low specific cell growth but not mild hypothermia improve
      specific r-protein productivity in chemostat culture of CHO cells.
AB  - In the biopharmaceutical sector, Chinese hamster ovary (CHO) cells have become
      the host of choice to produce recombinant proteins (r-proteins) due to their
      capacity for correct protein folding, assembly, and posttranslational
      modification. However, the production of therapeutic r-proteins in CHO cells is
      expensive and presents insufficient production yields for certain proteins.
      Effective culture strategies to increase productivity (qp) include a high glucose
      concentration in the medium and mild hypothermia (28-34  degrees C), but these
      changes lead to a reduced specific growth rate. To study the individual and
      combined impacts of glucose concentration, specific growth rate and mild
      hypothermia on culture performance and cell metabolism, we analyzed chemostat
      cultures of recombinant human tissue plasminogen activator (rh-tPA)-producing CHO
      cell lines fed with three glucose concentrations in feeding media (20, 30 and 40
      mM), at two dilution rates (0.01 and 0.018 1/h) and two temperatures (33 and 37 
      degrees C). The results indicated significant changes in cell growth, cell cycle
      distribution, metabolism, and rh-tPA productivity in response to the varying
      environmental culture conditions. High glucose feed led to constrained cell
      growth, increased specific rh-tPA productivity and a higher number of cells in
      the G2/M phase. Low specific growth rate and temperature (33  degrees C) reduced
      glucose consumption and lactate production rates. Our findings indicated that a
      reduced specific growth rate coupled with high feed glucose significantly
      improves r-protein productivity in CHO cells. We also observed that low
      temperature significantly reduced qp, but not cell growth when dilution rate was
      manipulated, regardless of the glucose concentration or dilution rate. In
      contrast, we determined that feed glucose concentration and consumption rate were
      the dominant aspects of the growth and productivity in CHO cells by using
      multivariate analysis.

PMID- 30114205
TI  - Enteric virome of Ethiopian children participating in a clean water intervention
      trial.
AB  - BACKGROUND: The enteric viruses shed by different populations can be influenced
      by multiple factors including access to clean drinking water. We describe here
      the eukaryotic viral genomes in the feces of Ethiopian children participating in
      a clean water intervention trial. METHODOLOGY/PRINCIPAL FINDINGS: Fecal samples
      from 269 children with a mean age of 2.7 years were collected from 14 villages in
      the Amhara region of Ethiopia, half of which received a new hand-dug water well.
      Feces from these villages were then analyzed in 29 sample pools using viral
      metagenomics. A total of 127 different viruses belonging to 3 RNA and 3 DNA viral
      families were detected. Picornaviridae family sequence reads were the most
      commonly found, originating from 14 enterovirus and 6 parechovirus genotypes plus
      multiple members of four other picornavirus genera (cosaviruses, saliviruses,
      kobuviruses, and hepatoviruses). Picornaviruses with nearly identical capsid VP1
      were detected in different pools reflecting recent spread of these viral strains.
      Next in read frequencies and positive pools were sequences from the Caliciviridae
      family including noroviruses GI and GII and sapoviruses. DNA viruses from
      multiple genera of the Parvoviridae family were detected (bocaviruses 1-4,
      bufavirus 3, and dependoparvoviruses), together with four species of adenoviruses
      and common anelloviruses shedding. RNA in the order Picornavirales and CRESS-DNA
      viral genomes, possibly originating from intestinal parasites or dietary sources,
      were also characterized. No significant difference was observed between the
      number of mammalian viruses shed from children from villages with and without a
      new water well. CONCLUSIONS: We describe an approach to estimate the efficacy of
      potentially virus transmission-reducing interventions and the first complete (DNA
      and RNA viruses) description of the enteric viromes of East African children. A
      wide diversity of human enteric viruses was found in both intervention and
      control groups. Mammalian enteric virome diversity was not reduced in children
      from villages with a new water well. This population-based sampling also provides
      a baseline of the enteric viruses present in Northern Ethiopia against which to
      compare future viromes.

PMID- 30114206
TI  - Setback distances for unconventional oil and gas development: Delphi study
      results.
AB  - Emerging evidence indicates that proximity to unconventional oil and gas
      development (UOGD) is associated with health outcomes. There is intense debate
      about "How close is too close?" for maintaining public health and safety. The
      goal of this Delphi study was to elicit expert consensus on appropriate setback
      distances for UOGD from human activity. Three rounds were used to identify and
      seek consensus on recommended setback distances. The 18 panelists were health
      care providers, public health practitioners, environmental advocates, and
      researchers/scientists. Consensus was defined as agreement of >=70% of panelists.
      Content analysis of responses to Round 1 questions revealed four categories:
      recommend setback distances; do not recommend setback distances; recommend
      additional setback distances for vulnerable populations; do not recommend
      additional setback distances for vulnerable populations. In Round 2, panelists
      indicated their level of agreement with the statements in each category using a
      five-point Likert scale. Based on emerging consensus, statements within each
      category were collapsed into seven statements for Round 3: recommend set back
      distances of <1/4 mile; 1/4-1/2 mile; 1-1 1/4 mile; and >= 2 mile; not feasible
      to recommend setback distances; recommend additional setbacks for vulnerable
      groups; not feasible to recommend additional setbacks for vulnerable groups. The
      panel reached consensus that setbacks of < 1/4 mile should not be recommended and
      additional setbacks for vulnerable populations should be recommended. The panel
      did not reach consensus on recommendations for setbacks between 1/4 and 2 miles.
      The results suggest that if setbacks are used the distances should be greater
      than 1/4 of a mile from human activity, and that additional setbacks should be
      used for settings where vulnerable groups are found, including schools, daycare
      centers, and hospitals. The lack of consensus on setback distances between 1/4
      and 2 miles reflects the limited health and exposure studies and need to better
      define exposures and track health.

PMID- 30114207
TI  - HCV elimination among people who inject drugs. Modelling pre- and post-WHO
      elimination era.
AB  - BACKGROUND: Elimination of hepatitis C virus (HCV) among people who inject drugs
      (PWID) is a costly investment, so strategies should not only focus on eliminating
      the disease, but also on preventing disease resurgence. The aims of this study
      are to compute the minimum necessary antiviral therapies to achieve elimination
      with and without the additional expansion of harm reduction (HR) programs and to
      examine the sustainability of HCV elimination after 2030 if treatment is
      discontinued. METHOD: We considered two types of epidemic (with low (30%) and
      high (50%) proportion of PWID who engage in sharing equipment (sharers)) within
      three baseline chronic HCV (CHC) prevalence settings (30%, 45% and 60%), assuming
      a baseline HR coverage of 40%. We define sustainable elimination strategies,
      those that could maintain eliminations results for a decade (2031-2040), in the
      absence of additional treatment. RESULTS: The model shows that the optimum
      elimination strategy is dependent on risk sharing behavior of the examined
      population. The necessary annual treatment coverage to achieve HCV elimination
      under 45% baseline CHC prevalence, without the simultaneous expansion of HR
      programs, ranges between 4.7-5.1%. Similarly, under 60% baseline CHC prevalence
      the needed treatment coverage varies from 9.0-10.5%. Increasing HR coverage from
      40% to 75%, reduces the required treatment coverage by 6.5-9.8% and 11.0-15.0%
      under 45% or 60% CHC prevalence, respectively. In settings with <=45% baseline
      CHC prevalence, expanding HR to 75% could prevent the disease from rebounding
      after elimination, irrespective of the type of the epidemic. In high chronic HCV
      prevalence, counseling interventions to reduce sharing are also needed to
      maintain the HCV incident cases in low levels. CONCLUSIONS: Harm reduction
      strategies have a vital role in HCV elimination strategy, as they reduce the
      required number of treatments to eliminate HCV and they provide sustainability
      after the elimination. The above underlines that HCV elimination strategies
      should be built upon the existing HR services, and argue for HR expansion in
      countries without services.

PMID- 30114209
TI  - Correction: FIN219/JAR1 and cryptochrome1 antagonize each other to modulate
      photomorphogenesis under blue light in Arabidopsis.
AB  - [This corrects the article DOI: 10.1371/journal.pgen.1007248.].

PMID- 30114208
TI  - Renoprotective effects of dexmedetomidine against ischemia-reperfusion injury in
      streptozotocin-induced diabetic rats.
AB  - BACKGROUND: Diabetic patients are susceptible to renal ischemia-reperfusion
      injury, which leads to perioperative complications. Activation of NOD-like
      receptor protein 3 (NLRP3) inflammasome participates in the development of
      diabetes, and contributes to renal ischemia-reperfusion injury. Dexmedetomidine
      (DEX), a highly selective alpha2-adrenoreceptor agonist, shows renoprotective
      effects against ischemia-reperfusion injury. We aimed to elucidate the effects,
      underlying mechanisms, and optimal timing of DEX treatment in diabetic rats.
      METHODS: Male Sprague-Dawley rats (n = 12 per group) were randomly divided into
      normal-sham, diabetes-sham, diabetes-ischemia-reperfusion-control, diabetes
      ischemia-reperfusion-DEX-pre-treatment, and diabetes-ischemia-reperfusion-DEX
      post-treatment groups. Renal ischemia-reperfusion injury was induced in diabetic
      rats by occlusion of both renal arteries for 45 min, followed by reperfusion for
      24 h. DEX (10 MUg/kg) was administered intraperitoneally 1 h before ischemia (pre
      treatment) or upon reperfusion (post-treatment). After reperfusion, renal tissue
      was biochemically and histopathologically evaluated. RESULTS: DEX treatment
      attenuated ischemia reperfusion-induced increase in NLRP3, caspase-1, IL-1beta,
      phospho-AKT, and phospho-ERK signaling. Moreover, oxidative stress injury,
      inflammatory reactions, apoptosis, and renal tubular damage were favorably
      modulated by DEX treatment. Furthermore, post-reperfusion treatment with DEX was
      significantly more effective than pre-treatment in modulating NLRP3 inflammasome,
      AKT and ERK signaling, and oxidative stress. CONCLUSIONS: This study shows that
      the protective effects of DEX in renal ischemia-reperfusion injury are preserved
      in diabetic conditions and may potentially provide a basis for the use of DEX in
      clinical treatment of renal ischemia-reperfusion injury.

PMID- 30114210
TI  - Hajj, Umrah, and the neglected tropical diseases.

PMID- 30114211
TI  - Effectiveness of Lonomia antivenom in recovery from the coagulopathy induced by
      Lonomia orientoandensis and Lonomia casanarensis caterpillars in rats.
AB  - In South America, accidental contact with Lepidoptera larvae can produce a
      diversity of reactions that vary from dermatological problems to severe
      hemorrhagic syndromes, such as those caused by contact with caterpillars of the
      genus Lonomia (Saturniidae). Lonomia venom can alter the hemostatic system and
      lead to renal failure, internal and brain bleeding, and in severe cases, death.
      The only specific treatment available for these envenomations is the Lonomia
      Antivenom (LAV) produced by the Butantan Institute, in Brazil, using an extract
      of Lonomia obliqua scoli as the antigen. LAV has been used to treat exposure to
      other Lonomia species across South America. However, no experimental studies have
      been performed to test the efficacy of LAV in neutralizing the venom of species
      other than L. obliqua found in Southern Brazil. In this study, we tested the
      effectiveness of LAV in reversing the hemostatic disturbances induced by
      injecting Lonomia casanarensis (Lca) and Lonomia orientoandensis (Lor) scolus
      extracts into rats and compared the effects to the case of L. obliqua (Lob)
      scolus extract-induced envenomation. Lca and Lor caterpillars were collected in
      Colombia, and some of them were reared to adults for identification. The Minimum
      Defibrinating Doses (MDD) of Lca and Lor were estimated. Rats were injected
      (i.d.) with a dose of 3 MDD per rat of each scolus extract and treated (i.v.)
      with 1.5 mL of LAV or 1.5 mL of saline. Twenty-four hours after the treatment,
      the fibrinogen levels and platelet counts had recovered to the hemostatic levels
      in the groups treated with LAV. The groups treated with the saline solution had
      fibrinogen levels and platelet counts at non-hemostatic levels.
      Thromboelastometric analyses confirmed these results. In conclusion, the results
      showed that LAV is effective at neutralizing the envenomation induced by Lca and
      Lor spine extracts in rats and restoring hemostasis.

PMID- 30114212
TI  - Association between passive tobacco exposure and caries in children and
      adolescents. A systematic review and meta-analysis.
AB  - To examine the available evidence on the association between exposure to tobacco
      use in the womb and in infancy and the presence of caries in primary and
      permanent dentition in children and adolescents. A systematic review was
      conducted through searches in 4 data bases (Pubmed, Scopus, Embase and Web of
      Science), complemented by hand-searching. Of the 559 articles identified, 400
      were duplicates. Finally, 28 articles were included in the qualitative review and
      21 in the meta-analysis. Their quality was assessed using the Newcastle-Ottawa
      scale. The quality was medium in 44% of the articles included and high in 56%.
      The overall meta-analysis gave a significant odds ratio (OR = 1.53, 95%
      confidence interval 1.39-1.68, Z test p-value = 0.000) and high heterogeneity (Q
      = 200.3, p = 0.000; I2 = 86.52%). Separate meta-analyses were also performed for
      three subgroups: exposure in the womb (prenatal) and caries in primary dentition,
      which resulted in a significant OR = 1.46 with a 95% CI of 1.41-1.52 (Z test p =
      0.000), without heterogeneity (Q = 0.91, p = 0.824; I2 = 0%); exposure in infancy
      (postnatal) and caries in primary dentition, with OR = 1.72 (95% CI 1.45-2.05)
      and high heterogeneity (Q = 76.59, p = 0.00; I2 = 83.01%); and postnatal exposure
      and caries in permanent dentition, with OR = 1.30 (95% CI 1.25-1.34) and no
      heterogeneity (Q = 4.48, p = 0.880; I2 = 0%). In children and adolescents, a
      significant though moderate association was found between passive tobacco
      exposure and caries.

PMID- 30114213
TI  - Urban versus rural residency and pancreatic cancer survival: A Danish nationwide
      population-based cohort study.
AB  - It is unknown whether urban versus rural residency affects pancreatic cancer
      survival in a universal tax-financed healthcare system. We conducted a
      nationwide, population-based cohort study of all patients diagnosed with
      pancreatic cancer in Denmark from 2004-2015. We used nationwide registries to
      collect information on characteristics, comorbidity, cancer-directed treatment,
      and vital status. We followed the patients from pancreatic cancer diagnosis until
      death, emigration, or 1 October 2017, whichever occurred first. We truncated at
      five years of follow up. We stratified patients into calendar periods according
      to year of diagnosis (2004-2007, 2008-2011, and 2012-2015). We used Cox
      proportional hazards model to compute hazard ratios (HRs) with associated 95%
      confidence intervals (CIs) of death, comparing patients in urban and rural areas.
      HRs were adjusted for age, sex, comorbidity, tumor stage, and localization. In a
      sub-analysis, we also adjusted for cancer-directed treatment. We included 10,594
      patients diagnosed with pancreatic cancer. Median age was 71 years (inter
      quartile range: 63-78 years), and half were men. The majority (61.7%) lived in an
      urban area at the time of diagnosis. When adjusting for potential confounders, we
      observed a better survival rate among pancreatic cancer patients residing in
      urban areas compared with rural areas (adjusted HR: 0.92; 95% CI: 0.87-0.98).
      When taking treatment into account, the association was unclear (adjusted HR:
      0.96; 95% CI: 0.88-1.04). Pancreatic cancer patients residing in urban areas had
      a slightly better survival rate compared with patients in rural areas.

PMID- 30114214
TI  - Genomic signatures of adaptive introgression and environmental adaptation in the
      Sheko cattle of southwest Ethiopia.
AB  - Although classified as an African taurine breed, the genomes of Sheko cattle are
      an admixture of Asian zebu and African taurine ancestries. They populate the
      humid Bench Maji zone in Sheko and Bench districts in the south-western part of
      Ethiopia and are considered as a trypanotolerant breed with high potential for
      dairy production. Here, we investigate the genome of Sheko cattle for candidate
      signatures of adaptive introgression and positive selection using medium density
      genome-wide SNP data. Following locus-ancestry deviation analysis, 15 and 72
      genome regions show substantial excess and deficiency in Asian zebu ancestry,
      respectively. Nine and 23 regions show candidate signatures of positive selection
      following extended haplotype homozygosity (EHH)-based analyses (iHS and Rsb),
      respectively. The results support natural selection before admixture for one iHS,
      one Rsb and three zebu ancestry-deficient regions. Genes and/or QTL associated
      with bovine immunity, fertility, heat tolerance, trypanotolerance and lactation
      are present within candidate selected regions. The identification of candidate
      regions under selection in Sheko cattle warrants further investigation of a
      larger sample size using full genome sequence data to better characterise the
      underlying haplotypes. The results can then support informative genomic breeding
      programmes to sustainably enhance livestock productivity in East African
      trypanosomosis infested areas.

PMID- 30114215
TI  - Characterising seasonal influenza epidemiology using primary care surveillance
      data.
AB  - Understanding the epidemiology of seasonal influenza is critical for healthcare
      resource allocation and early detection of anomalous seasons. It can be
      challenging to obtain high-quality data of influenza cases specifically, as
      clinical presentations with influenza-like symptoms may instead be cases of one
      of a number of alternate respiratory viruses. We use a new dataset of confirmed
      influenza virological data from 2011-2016, along with high-quality denominators
      informing a hierarchical observation process, to model seasonal influenza
      dynamics in New South Wales, Australia. We use approximate Bayesian computation
      to estimate parameters in a climate-driven stochastic epidemic model, including
      the basic reproduction number R0, the proportion of the population susceptible to
      the circulating strain at the beginning of the season, and the probability an
      infected individual seeks treatment. We conclude that R0 and initial population
      susceptibility were strongly related, emphasising the challenges of identifying
      these parameters. Relatively high R0 values alongside low initial population
      susceptibility were among the results most consistent with these data. Our
      results reinforce the importance of distinguishing between R0 and the effective
      reproduction number (Re) in modelling studies.

PMID- 30114216
TI  - Arterial compliance probe for cuffless evaluation of carotid pulse pressure.
AB  - OBJECTIVE: Assessment of local arterial properties has become increasingly
      important in cardiovascular research as well as in clinical domains. Vascular
      wall stiffness indices are related to local pulse pressure (DeltaP) level,
      mechanical and geometrical characteristics of the arterial vessel. Non-invasive
      evaluation of local DeltaP from the central arteries (aorta and carotid) is not
      straightforward in a non-specialist clinical setting. In this work, we present a
      method and system for real-time and beat-by-beat evaluation of local DeltaP from
      superficial arteries-a non-invasive, cuffless and calibration-free technique.
      METHODS: The proposed technique uses a bi-modal arterial compliance probe which
      consisted of two identical magnetic plethysmograph (MPG) sensors located at 23 mm
      distance apart and a single-element ultrasound transducer. Simultaneously
      measured local pulse wave velocity (PWV) and arterial dimensions were used in a
      mathematical model for calibration-free evaluation of local DeltaP. The proposed
      approach was initially verified using an arterial flow phantom, with invasive
      pressure catheter as the reference device. The developed porotype device was
      validated on 22 normotensive human subjects (age = 24.5 +/- 4 years). Two
      independent measurements of local DeltaP from the carotid artery were made during
      physically relaxed and post-exercise condition. RESULTS: Phantom-based
      verification study yielded a correlation coefficient (r) of 0.93 (p < 0.001) for
      estimated DeltaP versus reference brachial DeltaP, with a non-significant bias
      and standard deviation of error equal to 1.11 mmHg and +/-1.97 mmHg respectively.
      The ability of the developed system to acquire high-fidelity waveforms (dual MPG
      signals and ultrasound echoes from proximal and distal arterial walls) from the
      carotid artery was demonstrated by the in-vivo validation study. The group
      average beat-to-beat variation in measured carotid local PWV, arterial diameter
      parameters-distension and end-diastolic diameter, and local DeltaP were 4.2%,
      2.6%, 3.3%, and 10.2% respectively in physically relaxed condition. Consistent
      with the physiological phenomenon, local DeltaP measured from the carotid artery
      of young populations was, on an average, 22 mmHg lower than the reference DeltaP
      obtained from the brachial artery. Like the reference brachial blood pressure
      (BP) monitor, the developed prototype device reliably captured variations in
      carotid local DeltaP induced by an external intervention. CONCLUSION: This
      technique could provide a direct measurement of local PWV, arterial dimensions,
      and a calibration-free estimate of beat-by-beat local DeltaP. It can be
      potentially extended for calibration-free cuffless BP measurement and non
      invasive characterization of central arteries with locally estimated
      biomechanical properties.

PMID- 30114218
TI  - Individual-based genetic analyses support asexual hydrochory dispersal in Zostera
      noltei.
AB  - Dispersal beyond the local patch in clonal plants was typically thought to result
      from sexual reproduction via seed dispersal. However, evidence for the
      separation, transport by water, and re-establishment of asexual propagules
      (asexual hydrochory) is mounting suggesting other important means of dispersal in
      aquatic plants. Using an unprecedented sampling size and microsatellite genetic
      identification, we describe the distribution of seagrass clones along tens of km
      within a coastal lagoon in Southern Portugal. Our spatially explicit individual
      based sampling design covered 84 km2 and collected 3 185 Zostera noltei ramets
      from 803 sites. We estimated clone age, assuming rhizome elongation as the only
      mechanism of clone spread, and contrasted it with paleo-oceanographic sea level
      change. We also studied the association between a source of disturbance and the
      location of large clones. A total of 16 clones were sampled more than 10 times
      and the most abundant one was sampled 59 times. The largest distance between two
      samples from the same clone was 26.4 km and a total of 58 and 10 clones were
      sampled across more than 2 and 10 km, respectively. The number of extremely large
      clone sizes, and their old ages when assuming the rhizome elongation as the
      single causal mechanism, suggests other processes are behind the span of these
      clones. We discuss how the dispersal of vegetative fragments in a stepping-stone
      manner might have produced this pattern. We found higher probabilities to sample
      large clones away from the lagoon inlet, considered a source of disturbance. This
      study corroborates previous experiments on the success of transport and re
      establishment of asexual fragments and supports the hypothesis that asexual
      hydrochory is responsible for the extent of these clones.

PMID- 30114217
TI  - Assembly and comparative analysis of the complete mitochondrial genome sequence
      of Sophora japonica 'JinhuaiJ2'.
AB  - Sophora japonica L. (Faboideae, Leguminosae) is an important traditional Chinese
      herb with a long history of cultivation. Its flower buds and fruits contain
      abundant flavonoids, and therefore, the plants are cultivated for the industrial
      extraction of rutin. Here, we determined the complete nucleotide sequence of the
      mitochondrial genome of S. japonica 'JinhuaiJ2', the most widely planted variety
      in Guangxi region of China. The total length of the mtDNA sequence is 484,916 bp,
      with a GC content of 45.4%. Sophora japonica mtDNA harbors 32 known protein
      coding genes, 17 tRNA genes, and three rRNA genes with 17 cis-spliced and five
      trans-spliced introns disrupting eight protein-coding genes. The gene coding and
      intron regions, and intergenic spacers account for 7.5%, 5.8% and 86.7% of the
      genome, respectively. The gene profile of S. japonica mitogenome differs from
      that of the other Faboideae species by only one or two gene gains or losses. Four
      of the 17 cis-spliced introns showed distinct length variations in the Faboideae,
      which could be attributed to the homologous recombination of the short repeats
      measuring a few bases located precisely at the edges of the putative deletions.
      This reflects the importance of small repeats in the sequence evolution in
      Faboideae mitogenomes. Repeated sequences of S. japonica mitogenome are mainly
      composed of small repeats, with only 20 medium-sized repeats, and one large
      repeat, adding up to 4% of its mitogenome length. Among the 25 pseudogene
      fragments detected in the intergenic spacer regions, the two largest ones and
      their corresponding functional gene copies located in two different sets of
      medium-sized repeats, point to their origins from homologous recombinations. As
      we further observed the recombined reads associated with the longest repeats of
      2,160 bp with the PacBio long read data set of just 15 * in depth, repeat
      mediated homologous recombinations may play important role in the mitogenomic
      evolution of S. japonica. Our study provides insightful knowledge to the genetic
      background of this important herb species and the mitogenomic evolution in the
      Faboideae species.

PMID- 30114219
TI  - A competitive scheme for storing sparse representation of X-Ray medical images.
AB  - A competitive scheme for economic storage of the informational content of an X
      Ray image, as it can be used for further processing, is presented. It is
      demonstrated that sparse representation of that type of data can be encapsulated
      in a small file without affecting the quality of the recovered image. The
      proposed representation, which is inscribed within the context of data reduction,
      provides a format for saving the image information in a way that could assist
      methodologies for analysis and classification. The competitiveness of the
      resulting file is compared against the compression standards JPEG and JPEG2000.

PMID- 30114220
TI  - Human plague associated with Tibetan sheep originates in marmots.
AB  - The Qinghai-Tibet plateau is a natural plague focus and is the largest such focus
      in China. In this area, while Marmota himalayana is the primary host, a total of
      18 human plague outbreaks associated with Tibetan sheep (78 cases with 47 deaths)
      have been reported on the Qinghai-Tibet plateau since 1956. All of the index
      infectious cases had an exposure history of slaughtering or skinning diseased or
      dead Tibetan sheep. In this study, we sequenced and compared 38 strains of
      Yersinia pestis isolated from different hosts, including humans, Tibetan sheep,
      and M. himalayana. Phylogenetic relationships were reconstructed based on genome
      wide single-nucleotide polymorphisms identified from our isolates and reference
      strains. The phylogenetic relationships illustrated in our study, together with
      the finding that the Tibetan sheep plague clearly lagged behind the M. himalayana
      plague, and a previous study that identified the Tibetan sheep as a plague
      reservoir with high susceptibility and moderate sensitivity, indicated that the
      human plague was transmitted from Tibetan sheep, while the Tibetan sheep plague
      originated from marmots. Tibetan sheep may encounter this infection by contact
      with dead rodents or through being bitten by fleas originating from M. himalayana
      during local epizootics.

PMID- 30114221
TI  - Family history-based colorectal cancer screening in Australia: A modelling study
      of the costs, benefits, and harms of different participation scenarios.
AB  - BACKGROUND: The Australian National Bowel Cancer Screening Programme (NBCSP) was
      introduced in 2006. When fully implemented, the programme will invite people aged
      50 to 74 to complete an immunochemical faecal occult blood test (iFOBT) every 2
      years. METHODS AND FINDINGS: To investigate colorectal cancer (CRC) screening
      occurring outside of the NBCSP, we classified participants (n = 2,480) in the
      Australasian Colorectal Cancer Family Registry (ACCFR) into 3 risk categories
      (average, moderately increased, and potentially high) based on CRC family history
      and assessed their screening practices according to national guidelines. We
      developed a microsimulation to compare hypothetical screening scenarios (70% and
      100% uptake) to current participation levels (baseline) and evaluated clinical
      outcomes and cost for each risk category. The 2 main limitations of this study
      are as follows: first, the fact that our cost-effectiveness analysis was
      performed from a third-party payer perspective, which does not include indirect
      costs and results in overestimated cost-effectiveness ratios, and second, that
      our natural history model of CRC does not include polyp sojourn time, which
      determines the rate of cancerous transformation. Screening uptake was low across
      all family history risk categories (64%-56% reported no screening). For
      participants at average risk, 18% reported overscreening, while 37% of those in
      the highest risk categories screened according to guidelines. Higher screening
      levels would substantially reduce CRC mortality across all risk categories (95 to
      305 fewer deaths per 100,000 persons in the 70% scenario versus baseline). For
      those at average risk, a fully implemented NBCSP represented the most cost
      effective approach to prevent CRC deaths (AUS$13,000-16,000 per quality-adjusted
      life year [QALY]). For those at moderately increased risk, higher adherence to
      recommended screening was also highly cost-effective (AUS$19,000-24,000 per
      QALY). CONCLUSION: Investing in public health strategies to increase adherence to
      appropriate CRC screening will save lives and deliver high value for money.

PMID- 30114222
TI  - Self-reported functional status predicts post-operative outcomes in non-cardiac
      surgery patients with pulmonary hypertension.
AB  - BACKGROUND: Pulmonary hypertension (PHTN) is associated with increased post
      procedure morbidity and mortality. Pre-procedure echocardiography (ECHO) is a
      widely used tool for evaluation of these patients, but its accuracy in predicting
      post-procedure outcomes is unproven. Self-reported exercise tolerance has not
      been evaluated for operative risk stratification of PHTN patients. OBJECTIVE: We
      analyzed whether self-reported exercise tolerance predicts outcomes (hospital
      length-of-stay [LOS], mortality and morbidity) in PHTN patients (WHO Class I-V)
      undergoing anesthesia and surgery. METHODS AND FINDINGS: We reviewed 550 non
      cardiac, non-obstetric procedures performed on 370 PHTN patients at a single
      institution between 2007 and 2013. All patients had cardiac ECHO documented
      within 1 year prior to the procedure. Pre-procedure comorbidities and ECHO data
      were collected. Functional status (< or >= 4 metabolic equivalents of task
      [METs]) was assigned based on responses to standard patient interview questions
      during the pre-anesthesia clinic visit. Multiple logistic regression was used to
      develop a risk score model (Pulmonary Hypertension Outcome Risk Score; PHORS) and
      determine its value in predicting post-procedure outcomes. In an adjusted model,
      functional status <4 METs was independently associated with a LOS >7 days (p <
      .003), as were higher ASA class (p < .002), open surgical approach (p < .002),
      procedure duration > 2 hours (p < .001), and the absence of systemic hypertension
      (p = .012). PHORS Score >=2 was associated with an increased 30-day major
      complication rate (28.7% vs. 19.2%; p < 0.001) and ICU admission rate (8.6% s
      2.8%; p = .007), but no statistical difference in hospital readmissions rate
      (17.6% vs. 14.0%; p = .29), or mortality (3.5% vs. 1.4%; p = .75). Similar ECHO
      findings did not further improve outcome prediction. CONCLUSIONS: Poor functional
      status is associated with severe PHTN and predicts increased LOS and post
      procedure complications in patients with moderate to severe pulmonary
      hypertension with different etiologies. A risk assessment model predicts
      increased LOS with fair accuracy. A thorough evaluation of underlying etiologies
      of PHTN should be undertaken in every patient.

PMID- 30114223
TI  - High prevalence of hypertension in an agricultural village in Madagascar.
AB  - Elevated blood pressure presents a global health threat, with rates of
      hypertension increasing in low and middle-income countries. Lifestyle changes may
      be an important driver of these increases in blood pressure. Hypertension is
      particularly prevalent in African countries, though the majority of studies have
      focused on mainland Africa. We collected demographic and health data from 513
      adults living in a community in rural Madagascar. We used generalized linear
      mixed models to assess body mass index (BMI), age, sex, and attributes related to
      household composition and lifestyle as predictors of blood pressure and
      hypertension. The prevalence of hypertension in this cohort was 49.1% (both sexes
      combined: N = 513; females: 50.3%, N = 290; males: 47.5%, N = 223). Blood
      pressure, as well as hypertensive state, was positively associated with age and
      BMI. Lifestyle and household factors had no significant relationships with blood
      pressure. The prevalence of hypertension was similar to that found in urban
      centers of other African countries, yet almost double what has been previously
      found in Madagascar. Future research should investigate the drivers of
      hypertension in rural communities worldwide, as well as the lifestyle, cultural,
      and genetic factors that underlie variation in hypertension across space and
      time.

PMID- 30114224
TI  - Infliximab for pediatric patients with Crohn's disease: A Phase 3, open-label,
      uncontrolled, multicenter trial in Japan.
AB  - OBJECTIVES: The prevalence of pediatric Crohn's disease (CD) is increasing in
      Japan and other countries, and many patients are unresponsive to or do not
      tolerate current treatment options. This study aimed to investigate the efficacy,
      safety, and pharmacokinetic profile of infliximab (IFX) in pediatric patients
      with moderate-to-severe CD and inadequate response to existing treatment. STUDY
      DESIGN: This was an open-label, uncontrolled, multicenter Phase 3 study conducted
      at nine sites in Japan between April 2012 and March 2015. Pediatric patients
      (aged 6-17 years) with moderate-to-severe CD were treated with IFX 5 mg/kg at
      Weeks 0, 2, and 6, and at 8-week intervals thereafter until Week 46, with final
      evaluation at Week 54. IFX dose was increased to 10 mg/kg in patients who showed
      loss of response to IFX from Week 14 onwards. RESULTS: A total of 14 patients
      fulfilled eligibility criteria and were treated. Dose-escalation criteria were
      met by five patients who then received 10 mg/kg IFX. The remaining nine patients
      continued to receive an IFX dose of 5 mg/kg. IFX rapidly improved clinical
      symptoms and its effect was maintained for up to 54 weeks. Overall Pediatric
      Crohn's Disease Activity Index (PCDAI) response rate was 85.7%, and overall PCDAI
      remission rate was 64.3%. Three out of five patients who increased IFX dose
      regained PCDAI remission by retrieval of serum IFX concentration. Adverse events
      and serious adverse events occurred in 100.0% and 14.3% of patients,
      respectively. There was no substantial difference in the safety profiles of
      patients taking a constant dose of 5 mg/kg and those taking an increased dose of
      10 mg/kg. CONCLUSIONS: These findings support the effective use of IFX in the
      treatment of pediatric patients with CD where other treatments have proven
      ineffective.

PMID- 30114226
TI  - High protein intake is associated with low plasma NAD+ levels in a healthy human
      cohort.
AB  - High protein intake and reduced levels of the essential pyridine nucleotide
      nicotinamide adenine dinucleotide (NAD+) have both been independently associated
      with promotion of the ageing phenotype. However, it has not yet been shown
      whether these two independent observations are biochemically linked. To
      investigate this possibility, we used a cross-sectional study design of 100
      apparently healthy middle-aged males (n = 48) and females, in which we assessed
      average dietary intakes of multiple components using a validated questionnaire.
      We also analysed fasting blood levels of urea, NAD+ and its metabolites, and
      inflammation-linked biomarkers, including interleukin-6 (IL-6), Kynurenine (Kyn),
      and Tryptophan (Trp). One-way ANOVA and ANCOVA were then performed for
      statistical analysis. Our results have shown for the first time that plasma
      levels of NAD+ and Total NAD(H) were lower with increasing protein intake (F (2,
      92) = 4.61, P = 0.012; F (2, 92) = 4.55, P = 0.013, respectively). The associated
      decrease in NAD+ and NAD(H) levels was even stronger with increasing plasma
      levels of the protein breakdown product urea (F (2, 93) = 25.11, P<=0.001; F (2,
      93) = 21.10, P<=0.001). These associations were all independent of age, gender
      and energy intake. However, no significant association was observed between
      protein intake or plasma urea, and plasma levels of NAD+ metabolites. We also
      observed that plasma levels of the inflammatory cytokine IL-6, and both Kyn, and
      Trp, but not the Kyn/Trp ratio were higher with increasing plasma urea levels (F
      (2, 94) = 3.30, P = 0.041; F (2, 95) = 7.41, P<=0.001; F (2, 96) = 4.23, P =
      0.017, respectively). These associations were dependent on eGFR and energy
      intake, except for the urea and Trp association that was independent of all. In
      conclusion, we report for the first time, a novel association between protein
      intake, its metabolism, and plasma NAD+ levels with a possible link to
      inflammation. These findings provide further insight into how protein restriction
      may contribute to the anti-ageing process observed in several studies.

PMID- 30114228
TI  - High-resolution acoustic surveys with diving gliders come at a cost of aliasing
      moving targets.
AB  - Underwater gliders are autonomous robots that follow a slow, see-saw path and may
      be deployed for months on end. Gliders have a dramatically lower payload capacity
      than research vessels and are thus limited to more simple instrumentation. They
      have the advantage, however, of being deployable for long periods of time without
      the high running costs of a ship. Recent years have seen development of the use
      of gliders to undertake acoustic surveys of biomass in the pelagic environment,
      highlighting their potential to fill future survey gaps. Here it is shown, using
      simulation of sampling, that gliders can resolve acoustic targets at greater
      resolutions than ships, due to their diving pattern, but that survey accuracy is
      strongly dependent on the speed of the target.

PMID- 30114225
TI  - Activation of Nrf2 in the liver is associated with stress resistance mediated by
      suppression of the growth hormone-regulated STAT5b transcription factor.
AB  - The transcription factor Nrf2 (encoded by Nfe2l2) induces expression of numerous
      detoxifying and antioxidant genes in response to oxidative stress. The
      cytoplasmic protein Keap1 interacts with and represses Nrf2 function.
      Computational approaches were developed to identify factors that modulate Nrf2 in
      a mouse liver gene expression compendium. Forty-eight Nrf2 biomarker genes were
      identified using profiles from the livers of mice in which Nrf2 was activated
      genetically in Keap1-null mice or chemically by a potent activator of Nrf2
      signaling. The rank-based Running Fisher statistical test was used to determine
      the correlation between the Nrf2 biomarker genes and a test set of 81 profiles
      with known Nrf2 activation status demonstrating a balanced accuracy of 96%. For a
      large number of factors examined in the compendium, we found consistent
      relationships between activation of Nrf2 and feminization of the liver
      transcriptome through suppression of the male-specific growth hormone (GH)
      regulated transcription factor STAT5b. The livers of female mice exhibited higher
      Nrf2 activation than male mice in untreated or chemical-treated conditions. In
      male mice, Nrf2 was activated by treatment with ethinyl estradiol, whereas in
      female mice, Nrf2 was suppressed by treatment with testosterone. Nrf2 was
      activated in 5 models of disrupted GH signaling containing mutations in Pit1,
      Prop1, Ghrh, Ghrhr, and Ghr. Out of 59 chemical treatments that activated Nrf2,
      36 exhibited STAT5b suppression in the male liver. The Nrf2-STAT5b coupling was
      absent in in vitro comparisons of chemical treatments. Treatment of male and
      female mice with 11 chemicals that induce oxidative stress led to activation of
      Nrf2 to greater extents in females than males. The enhanced basal and inducible
      levels of Nrf2 activation in females relative to males provides a molecular
      explanation for the greater resistance often seen in females vs. males to age
      dependent diseases and chemical-induced toxicity.

PMID- 30114227
TI  - Generation and characterisation of recombinant FMDV antibodies: Applications for
      advancing diagnostic and laboratory assays.
AB  - Foot-and-mouth disease (FMD) affects economically important livestock and is one
      of the most contagious viral diseases. The most commonly used FMD diagnostic
      assay is a sandwich ELISA. However, the main disadvantage of this ELISA is that
      it requires anti-FMD virus (FMDV) serotype-specific antibodies raised in small
      animals. This problem can be, in part, overcome by using anti-FMDV monoclonal
      antibodies (MAbs) as detecting reagents. However, the long-term use of MAbs may
      be problematic and they may need to be replaced. Here we have constructed
      chimeric antibodies (mouse/rabbit D9) and Fabs (fragment antigen-binding)
      (mouse/cattle D9) using the Fv (fragment variable) regions of a mouse MAb, D9
      (MAb D9), which recognises type O FMDV. The mouse/rabbit D9 chimeric antibody
      retained the FMDV serotype-specificity of MAb D9 and performed well in a FMDV
      detection ELISA as well as in routine laboratory assays. Cryo-electron microscopy
      analysis confirmed engagement with antigenic site 1 and peptide competition
      studies identified the aspartic acid at residue VP1 147 as a novel component of
      the D9 epitope. This chimeric expression approach is a simple but effective way
      to preserve valuable FMDV antibodies, and has the potential for unlimited
      generation of antibodies and antibody fragments in recombinant systems with the
      concomitant positive impacts on the 3Rs (Replacement, Reduction and Refinement)
      principles.

PMID- 30114229
TI  - Determinants of bone damage: An ex-vivo study on porcine vertebrae.
AB  - Bone's resistance to fracture depends on several factors, such as bone mass,
      microarchitecture, and tissue material properties. The clinical assessment of
      bone strength is generally performed by Dual-X Ray Photon Absorptiometry (DXA),
      measuring bone mineral density (BMD) and trabecular bone score (TBS). Although it
      is considered the major predictor of bone strength, BMD only accounts for about
      70% of fragility fractures, while the remaining 30% could be described by bone
      "quality" impairment parameters, mainly related to tissue microarchitecture. The
      assessment of bone microarchitecture generally requires more invasive techniques,
      which are not applicable in routine clinical practice, or X-Ray based imaging
      techniques, requiring a longer post-processing. Another important aspect is the
      presence of local damage in the bony tissue that may also affect the prediction
      of bone strength and fracture risk. To provide a more comprehensive analysis of
      bone quality and quantity, and to assess the effect of damage, here we adopt a
      framework that includes clinical, morphological, and mechanical analyses, carried
      out by means of DXA, MUCT and mechanical compressive testing, respectively. This
      study has been carried out on trabecular bones, taken from porcine trabecular
      vertebrae, for the similarity with human lumbar spine. This study confirms that
      no single method can provide a complete characterization of bone tissue, and the
      combination of complementary characterization techniques is required for an
      accurate and exhaustive description of bone status. BMD and TBS have shown to be
      complementary parameters to assess bone strength, the former assessing the bone
      quantity and resistance to damage, and the latter the bone quality and the
      presence of damage accumulation without being able to predict the risk of
      fracture.

PMID- 30114230
TI  - Cost-effectiveness of everolimus-eluting versus bare-metal stents in ST-segment
      elevation myocardial infarction: An analysis from the EXAMINATION randomized
      controlled trial.
AB  - BACKGROUND: Use of everolimus-eluting stents (EES) has proven to be clinically
      effective and safe in patients with ST-segment elevation myocardial infarction
      but it remains unclear whether it is cost-effective compared to bare-metal stents
      (BMS) in the long-term. We sought to assess the cost-effectiveness of EES versus
      BMS based on the 5-year results of the EXAMINATION trial, from a Spanish health
      service perspective. METHODS: Decision analysis of the use of EES versus BMS was
      based on the patient-level clinical outcome data of the EXAMINATION trial. The
      analysis adopted a lifelong time horizon, assuming that long-term survival was
      independent of the initial treatment strategy after the end of follow-up. Life
      expectancy, health-state utility scores and unit costs were extracted from
      published literature and publicly available sources. Non-parametric bootstrapping
      was combined with probabilistic sensitivity analysis to co-assess the impact of
      patient-level variation and parameter uncertainty. The main outcomes were total
      costs and quality-adjusted life-years. The incremental cost-effectiveness ratio
      was expressed as cost per quality-adjusted life-years gained. Costs and effects
      were discounted at 3%. RESULTS: The model predicted an average survival time in
      patients receiving EES and BMS of 10.52 and 10.38 undiscounted years,
      respectively. Over the life-long time horizon, the EES strategy was ?430 more
      costly than BMS (?8,305 vs. ?7,874), but went along with incremental gains of
      0.10 quality-adjusted life-years. This resulted in an average incremental cost
      effectiveness ratio over all simulations of ?3,948 per quality-adjusted life
      years gained and was below a willingness-to-pay threshold of ?25,000 per quality
      adjusted life-years gained in 86.9% of simulation runs. CONCLUSIONS: Despite
      higher total costs relative to BMS, EES appeared to be a cost-effective therapy
      for ST-segment elevation myocardial infarction patients due to their incremental
      effectiveness. Predicted incremental cost-effectiveness ratios were below
      generally acceptable threshold values.

PMID- 30114231
TI  - Curvature-driven spatial patterns in growing 3D domains: A mechanochemical model
      for phyllotaxis.
AB  - Here we discuss the formation of phyllotactic patterns in the shoot apical
      meristem (SAM) of plants, where the spatial distribution of the phytohormone
      auxin determines phyllotaxis in a domain that is growing and changing in time. We
      assume that the concentration of auxin modifies the mechanical properties of the
      domain and that the mechanical stress field in the SAM orients the flux of auxin.
      To study this problem we propose a mechanism for pattern formation in growing
      domains with variable curvature. The dynamics of chemicals is modeled by a
      reaction-diffusion system that produces a three dimensional pattern of chemical
      concentrations that changes the stress field in the domain while growing. The
      growth process is modeled by a phase-field order parameter which determines the
      location of the boundaries of the domain. This field is coupled to the chemical
      concentration through a curvature term that affects the local mechanical stress
      in the domain. The local stress changes in turn modify the chemical patterns. Our
      model constitutes a useful and novel approach in theoretical biology, as many
      developmental processes in organisms seem to be affected by the changes of
      curvature, size, mechanical stress and other physical aspects. Several patterns
      seen in many plants are reproduced under certain conditions by our model.

PMID- 30114233
TI  - Correction: A collaborative translational research framework for evaluating and
      implementing the appropriate use of human genome sequencing to improve health.
AB  - [This corrects the article DOI: 10.1371/journal.pmed.1002631.].

PMID- 30114232
TI  - Historical baselines in marine bioinvasions: Implications for policy and
      management.
AB  - The human-mediated introduction of marine non-indigenous species is a centuries-
      if not millennia-old phenomenon, but was only recently acknowledged as a potent
      driver of change in the sea. We provide a synopsis of key historical milestones
      for marine bioinvasions, including timelines of (a) discovery and understanding
      of the invasion process, focusing on transfer mechanisms and outcomes, (b)
      methodologies used for detection and monitoring, (c) approaches to ecological
      impacts research, and (d) management and policy responses. Early (until the mid
      1900s) marine bioinvasions were given little attention, and in a number of cases
      actively and routinely facilitated. Beginning in the second half of the 20th
      century, several conspicuous non-indigenous species outbreaks with strong
      environmental, economic, and public health impacts raised widespread concerns and
      initiated shifts in public and scientific perceptions. These high-profile
      invasions led to policy documents and strategies to reduce the introduction and
      spread of non-indigenous species, although with significant time lags and limited
      success and focused on only a subset of transfer mechanisms. Integrated, multi
      vector management within an ecosystem-based marine management context is urgently
      needed to address the complex interactions of natural and human pressures that
      drive invasions in marine ecosystems.

PMID- 30114234
TI  - Molecular characterization of a novel Aureusvirus infecting elderberry (Sambucus
      nigra L.).
AB  - A novel virus infecting elderberry was identified by high-throughput Illumina
      sequencing of double strand RNAs isolated form elderberry leaves. The complete
      genome sequence obtained (4512 nucleotides in length) shows an organization
      typical for aureusviruses, with five open reading frames (ORFs) and the typical
      ORF1-RT expression by the readthrough of an amber stop codon. The analysis of the
      RNA-dependent RNA polymerase (RdRp) and coat protein (CP) sequences showed the
      highest identity (respectively 75.7% and 55%) with the corresponding amino acid
      sequences of Pothos latent virus. These two values, below the species demarcation
      criteria for the genus, indicate that the detected virus is a new member of genus
      Aureusvirus, family Tombusviridae, with the proposed name Elderberry aureusvirus
      1 (ElAV1). A survey confirmed the wide distribution of ElAV1 in elderberry in the
      Czech Republic. Phylogenetic analyses of RdRp and CP sequences showed distinct
      microevolution of geographically separated isolates, with a tendency for isolates
      coming from close localities or from the same region to cluster together but
      heterogeneity of viral populations down to a local scale was also observed. The
      symptomatology of the new virus is not fully clear, but many infected trees were
      either asymptomatic or showed mild chlorotic mosaics. More severe symptoms,
      potentially impacting yields of flowers or berries, were observed in plants with
      mixed infections of ElAV1 and other elderberry viruses. Further efforts are now
      needed to determine ElAV1 prevalence outside the Czech Republic and to unravel
      its epidemiology.

PMID- 30114235
TI  - Diffusion weighted and dynamic contrast enhanced MRI as an imaging biomarker for
      stereotactic ablative body radiotherapy (SABR) of primary renal cell carcinoma.
AB  - PURPOSE: To explore the utility of diffusion and perfusion changes in primary
      renal cell carcinoma (RCC) after stereotactic ablative body radiotherapy (SABR)
      as an early biomarker of treatment response, using diffusion weighted (DWI) and
      dynamic contrast enhanced (DCE) MRI. METHODS: Patients enrolled in a prospective
      pilot clinical trial received SABR for primary RCC, and had DWI and DCE MRI
      scheduled at baseline, 14 days and 70 days after SABR. Tumours <5cm diameter
      received a single fraction of 26 Gy and larger tumours received three fractions
      of 14 Gy. Apparent diffusion coefficient (ADC) maps were computed from DWI data
      and parametric and pharmacokinetic maps were fitted to the DCE data. Tumour
      volumes were contoured and statistics extracted. Spearman's rank correlation
      coefficients were computed between MRI parameter changes versus the percentage
      tumour volume change from CT at 6, 12 and 24 months and the last follow-up
      relative to baseline CT. RESULTS: Twelve patients were eligible for DWI analysis,
      and a subset of ten patients for DCE MRI analysis. DCE MRI from the second follow
      up MRI scan showed correlations between the change in percentage voxels with
      washout contrast enhancement behaviour and the change in tumour volume (rho =
      0.84, p = 0.004 at 12 month CT, rho = 0.81, p = 0.02 at 24 month CT, and rho =
      0.89, p = 0.001 at last follow-up CT). The change in mean initial rate of
      enhancement and mean Ktrans at the second follow-up MRI scan were positively
      correlated with percent tumour volume change at the 12 month CT onwards (rho =
      0.65, p = 0.05 and rho = 0.66, p = 0.04 at 12 month CT respectively). Changes in
      ADC kurtosis from histogram analysis at the first follow-up MRI scan also showed
      positive correlations with the percentage tumour volume change (rho = 0.66, p =
      0.02 at 12 month CT, rho = 0.69, p = 0.02 at last follow-up CT), but these
      results are possibly confounded by inflammation. CONCLUSION: DWI and DCE MRI
      parameters show potential as early response biomarkers after SABR for primary
      RCC. Further prospective validation using larger patient cohorts is warranted.

PMID- 30114236
TI  - Identifying feasible operating regimes for early T-cell recognition: The speed,
      energy, accuracy trade-off in kinetic proofreading and adaptive sorting.
AB  - In the immune system, T cells can quickly discriminate between foreign and self
      ligands with high accuracy. There is evidence that T-cells achieve this
      remarkable performance utilizing a network architecture based on a generalization
      of kinetic proofreading (KPR). KPR-based mechanisms actively consume energy to
      increase the specificity beyond what is possible in equilibrium. An important
      theoretical question that arises is to understand the trade-offs and fundamental
      limits on accuracy, speed, and dissipation (energy consumption) in KPR and its
      generalization. Here, we revisit this question through numerical simulations
      where we simultaneously measure the speed, accuracy, and energy consumption of
      the KPR and adaptive sorting networks for different parameter choices. Our
      simulations highlight the existence of a "feasible operating regime" in the speed
      energy-accuracy plane where T-cells can quickly differentiate between foreign and
      self ligands at reasonable energy expenditure. We give general arguments for why
      we expect this feasible operating regime to be a generic property of all KPR
      based biochemical networks and discuss implications for our understanding of the
      T cell receptor circuit.

PMID- 30114237
TI  - Early life predictors of midlife allostatic load: A prospective cohort study.
AB  - BACKGROUND: Allostatic load has been suggested as a pathway through which
      experiences become biologically embedded to influence health. Research on
      childhood predictors of allostatic load has focused on socioeconomic and
      psychosocial exposures, while few studies include prospective measures of
      biomedical exposures. Further, findings on sex differences in the association of
      childhood predictors with various health outcomes related to allostatic load are
      ambiguous. AIMS: To examine the influence of early life biomedical and social
      factors in the first year of life on midlife allostatic load, assessing potential
      sex differences. METHODS: This prospective cohort study includes early life
      information collected at birth and a one year examination for 1,648 members of
      the Copenhagen Perinatal Cohort who also participated in the Copenhagen Aging and
      Midlife Biobank study (aged 49-52 years, 56% women). Allostatic load based on 14
      biomarkers was selected as a measure of midlife health status. Early life factors
      were categorized as predominantly biomedical or social, and their associations
      with midlife allostatic load were examined in domain-specific and combined sex
      stratified multiple regression models. RESULTS: The biomedical factors model
      explained 6.6% of the variance in midlife allostatic load in men and 6.7% in
      women, while the social model explained 4.1% of the variance in men and 7.3% in
      women. For both sexes, parental socioeconomic position at one year and maternal
      BMI significantly predicted midlife allostatic load in a model containing all
      early life factors. For women, additional significant predictors were
      complications at birth, birth weight and not living with parents at one year.
      CONCLUSION: The results confirm an association of lower childhood socioeconomic
      position with higher adult allostatic load while demonstrating the importance of
      other prenatal and early life exposures and highlighting potential sex
      differences.

PMID- 30114238
TI  - Lung cancer in idiopathic pulmonary fibrosis: A systematic review and meta
      analysis.
AB  - BACKGROUND: There are many epidemiological pieces of evidence that show IPF
      patients have the highest risk of lung cancer. We conducted a systematic review
      of all published data to define the characteristics of lung cancer that develops
      in IPF by performing a meta-analysis. METHOD: This study was performed based on
      the PRISMA guideline. Documents gathered by searching through the Web of
      Sciences, Scopus, PubMed/Medline, OVID, and COCHRANE databases which published
      before 03/25/2018 that related to lung cancer in IPFs' patients. Articles were
      searched using standard keywords as well as Mesh and Mesh Entry and all
      probabilistic combinations of words using Boolean operators. Data searching,
      extracting and quality appraising were done by two researchers, independently. At
      last, Random-effects size based on Cochrane test and I2 were used. The review
      protocol has been registered in PROSPERO with ID: CRD42018094037. RESULTS: Based
      on the meta-analysis conducted in 35 (0.18%) included studies, the total sample
      size of patients with IPF was estimated 131947 among whom 6384 had LC. The total
      rate of LC prevalence in IPF patients was estimated to be 13.54% (95% CI: 10.43
      17.4) that was significantly 9 times higher in men vs. Women and smoker vs. non
      smoker. Highest to lowest prevalence of cellular (histological) subtypes of lung
      cancer in IPF were SQCC (37.82%), ADC (30.79%), SmCC (20.48%), LCC (5.21%), and
      ADQC (4.81%), respectively. The highest and lowest stage of lung cancer in IPF
      patients was estimated at III and II, respectively. The highest involvement
      location of lung cancer in IPF patients was in the Peripheral. Also, the
      prevalence of the tumor region involved from the highest to the lowest was
      estimated to be in the RLL, LLL, RUL and LUL regions. CONCLUSIONS: Lung cancer in
      IPF, most commonly SQCC, presents in elderly heavy smokers with a male, locating
      in peripheral regions and the lower part of lung predominance.

PMID- 30114239
TI  - Atopic diseases/diathesis and subsequent ischemic stroke among patients with
      bipolar disorder: A nationwide longitudinal study.
AB  - INTRODUCTION: Previous studies have suggested that both bipolar disorder and
      atopy are associated with an increased risk of stroke. However, the role of
      atopic diseases/diathesis in the risk of stroke among patients with bipolar
      disorder remains unclear. METHODS: Using Taiwan's National Health Insurance
      Research Database, we selected 55,593 patients with bipolar disorder between 2002
      and 2008, divided them into patients with atopic diseases/diathesis (n = 21,050)
      and patients without atopic diseases/diathesis (n = 34,543), and observed them
      until the end of 2011. Patients who experienced a stroke during the follow-up
      period were identified. RESULTS: Patients with bipolar disorder and atopic
      diseases/diathesis had an elevated risk of ischemic stroke (hazard ratio [HR]:
      1.44, 95% confidence interval [CI]: 1.25-1.59) compared with patients with only
      bipolar disorder; a dose-dependent relationship was observed between the number
      of allergic comorbidities and the risk of ischemic stroke (1 atopic disease, HR:
      1.30, 95% CI: 1.13-1.49; 2 atopic diseases, HR: 1.59, 95% CI: 1.33-1.91; >= 3
      atopic diseases, HR: 2.09, 95% CI: 1.50-2.91).The role of atopic diseases in the
      risk of hemorrhagic stroke among patients with bipolar disorder was
      nonsignificant (HR: 0.84, 95% CI: 0.64-1.09). CONCLUSIONS: Patients with bipolar
      disorder and atopic diseases/diathesis are more prone to ischemic stroke later in
      life than are those without atopic diseases/diathesis. Further study is required
      to investigate the underlying mechanism linking atopy, bipolar disorder, and
      stroke.

PMID- 30114240
TI  - The impact of cardiopulmonary resuscitation (CPR) manikin chest stiffness on
      motivation and CPR performance measures in children undergoing CPR training-A
      prospective, randomized, single-blind, controlled trial.
AB  - BACKGROUND: Cardio-pulmonary-resuscitation (CPR) training starting at the age of
      12 years is recommended internationally. Training younger children is not
      recommended because young children lack the physical ability to perform adequate
      CPR and discouragement to perform CPR later is apprehended. The aim of this study
      was to answer the following questions: Are younger children discouraged after CPR
      training? Is discouragement caused by their lack in physical ability to perform
      adequate chest compressions on a standard manikin and would the use of manikins
      with a reduced resistance affect their motivation or performance? METHODS: We
      investigated the motivation and CPR performance of children aged 8-13 years after
      CPR training on manikins of different chest stiffness in a prospective,
      randomized, single-blind, controlled trial. 322 children underwent randomization
      and received 30 minutes CPR training in small groups at school. We used two
      optically identical resuscitation manikins with different compression resistances
      of 45kg and 30kg. Motivation was assessed with a self-administered questionnaire.
      Performance was measured with the Resusci(r)Anne SkillReporterTM. FINDINGS:
      Motivation after the training was generally high and there was no difference
      between the two groups in any of the questionnaire items on motivation: Children
      had fun (98 vs. 99%; P = 0.32), were interested in the training (99 vs. 98%; P =
      0.65), and were glad to train resuscitation again in the future (89 vs. 91%; P =
      0.89). CPR performance was generally poor (median compression score (8, IQR 1-45
      and 29, IQR 11-54; P<0.001) and the mean compression depth was lower in the 45kg
      resistance than in the 30kg-resistance group (33+/-10mm vs. 41+/-9; P<0.001).
      CONCLUSIONS: Compression resistances of manikins, though influencing CPR
      performance, did not discourage 8 to 13 year old children after CPR training. The
      findings refute the view that young children are discouraged when receiving CPR
      training even though they are physically not able to perform adequate CPR.

PMID- 30114241
TI  - cGAS and STING: At the intersection of DNA and RNA virus-sensing networks.

PMID- 30114242
TI  - Is guideline-adherent prescribing associated with quality of life in patients
      with type 2 diabetes?
AB  - BACKGROUND: Guideline-adherent prescribing for treatment of multiple risk factors
      in type 2 diabetes (T2D) patients is expected to improve clinical outcomes.
      However, the relationship to Health-Related Quality of Life (HRQoL) is not
      straightforward since guideline-adherent prescribing can increase medication
      burden. OBJECTIVES: To test whether guideline-adherent prescribing and disease
      specific medication burden are associated with HRQoL in patients with T2D.
      METHODS: Cross-sectional study including 1,044 T2D patients from the e
      VitaDM/ZODIAC study in 2012 in the Netherlands. Data from the diabetes visit,
      such as laboratory and physical examinations and prescribed medication, and from
      two HRQoL questionnaires, the EuroQol 5 Dimensions 3 Levels (EQ5D-3L) and the
      World Health Organization Well-Being Index (WHO-5) were collected. Twenty
      indicators assessing prescribing of recommended glucose lowering drugs, statins,
      antihypertensives and renin-angiotensin-aldosterone system (RAAS)-inhibitors and
      potentially inappropriate drugs from a validated diabetes indicator set were
      included. Disease-specific medication burden was assessed using a modified
      version of the Medication Regimen Complexity Index (MRCI). Associations were
      tested with regression models, adjusting for age, gender, diabetes duration,
      comorbidity, body mass index and smoking. RESULTS: The mean MRCI was 7.1, the
      median EQ5D-3L-score was 0.86 and the mean WHO-5 score was 72. Seven indicators
      included too few patients and were excluded from the analysis. The remaining
      thirteen indicators focusing on recommended start, intensification, current and
      preferred use of glucose lowering drugs, statins, antihypertensives, RAAS
      inhibitors, and on inappropriate prescribing of glibenclamide and dual RAAS
      blockade were not significantly associated with HRQoL. Finally, also the MRCI was
      not associated with HRQoL. CONCLUSIONS: We found no evidence for associations
      between guideline-adherent prescribing or disease-specific medication burden and
      HRQoL in T2D patients. This gives no rise to refrain from prescribing intensive
      treatment in T2D patients as recommended, but the interpretation of these results
      is limited by the cross-sectional study design and the selection of patients
      included in some indicators.

PMID- 30114243
TI  - Cryopreservation effects on a viable sperm sterlet (Acipenser ruthenus)
      subpopulation obtained by a Percoll density gradient method.
AB  - In many fish species, sperm cryopreservation has deleterious effects and leads to
      a significant decrease in spermatozoa viability. However, the effect of
      cryopreservation on sperm cells that survive this process and are still viable is
      not fully understood. The objective of this study was to compare the viability
      and proteomes of fresh and cryopreserved sterlet (Acipenser ruthenus) sperm
      samples before and after live-dead cell separation using Percoll density gradient
      centrifugation. Both fresh and cryopreserved sperm samples were divided into two
      groups (with or without application of Percoll separation). At each step of the
      experiment, sperm quality was evaluated by video microscopy combined with
      integrated computer-assisted sperm analysis software and flow cytometry for live
      dead sperm viability analysis. Sperm motility and the percentage of live cells
      were reduced in the cryopreserved group compared to the fresh group from 89% to
      33% for percentage of motility and from 96% to 70% for live cells. Straight line
      velocity and linearity of track were significantly lower in cryopreserved samples
      than in those separated by Percoll before and after cryopreservation. However,
      the percentages of motile and live spermatozoa were higher than 90% in samples
      subjected to Percoll separation. Proteomic analysis of spermatozoa by two
      dimensional differences in-gel electrophoresis coupled with matrix-assisted laser
      desorption/ionization time-of-flight/time-of-flight mass spectrometry revealed
      that 20 protein spot abundances underwent significant changes in cryopreserved
      samples compared to fresh ones. However, only one protein spot was significantly
      altered when samples before and after cryopreservation followed by Percoll
      separation were compared. Thus, the results of this study show that
      cryopreservation leads to minimal proteomic changes in the spermatozoa
      population, retaining high motility and viability parameters. The results also
      suggest that global differences in protein profiles between unselected fresh and
      cryopreserved samples are mainly due to protein loss or changes in the lethal and
      sublethal damaged cell subpopulations.

PMID- 30114244
TI  - Effective linkage from point of HIV testing to care and treatment in Tanga
      region, Tanzania.
AB  - BACKGROUND: Linkage to care and treatment is an important part of efforts to
      accelerate HIV prevention, treatment, care, and support. It offers an opportunity
      for PLHIV to receive information and services in a timely manner. Clients who
      present late for HIV care and treatment may miss out on timely initiation of
      prophylaxis and ART, which may accelerate disease progression and lead to an
      increased rate of HIV transmission within the community. The objective of this
      study was to determine the factors influencing effective linkages of newly
      diagnosed PLHIV from the point of testing to entry in care and treatment centres
      (CTCs) in Tanga Region, Tanzania. METHODS: This cross-sectional study examined
      five clinics with a high volume of clients in each of the three districts in
      Tanga Region. All adults ages 18 years and above at the time of CTC enrolment,
      between 2010 and 2014, were eligible to participate in the study. The study
      engaged both secondary and primary data. To complement the secondary data, mixed
      methods were applied in primary data collection. Using a structured
      questionnaire, interviews with the sampled CTC clients while focus group
      discussions with healthcare providers and in-depth interviews with CTC clients.
      The qualitative data were analysed using a thematic analysis framework. The
      outcome of interest was whether a client enrolled in a CTC within three months of
      his or her first positive HIV test. A logistic regression model was used to
      determine factors associated with effective linkage of newly diagnosed HIV
      clients to CTC. RESULTS: A total of 16,041 adults from the three study districts
      were enrolled at a CTC from 2010 to 2014. A total of 1,096 clients from the
      sampled CTCs were recruited into the study for interview. The characteristics of
      these clients were representative of the larger group (16,041). The majority
      (72.4%) were female. More than half (52.1%) were married, and almost a quarter
      (21.2%) were single. The majority (59.6%) of participants completed primary
      education and almost half (45.1%) were subsistence farmers. The median CD4 count
      at enrolment was 218 (87-397) cells/mL with more than half (56.3%) having CD4
      counts of less than 350 cells per millilitre (mL). Nearly all (91%) of the
      clients presented at a CTC within three months of receiving a positive HIV test.
      In a multivariate analysis, factors that remained significantly associated with
      early entry in CTC were level of education, CD4 count, and point of diagnosis.
      Participants' responses were consistent with many of the factors explained by
      participants to be barriers to effective linkages and referrals repeated in the
      FGDs and IDIs across the study sites. For instance, FGD respondent expressed that
      clients were worried about stigma from their relatives, which creates a delay in
      seeking treatment. CONCLUSION: Although the rate of early entry in care and
      treatment services is high, surprisingly was a marked increase in those who
      waited more than three months to seek treatment. To meet the target, issues such
      as disclosure and stigma need to be addressed.

PMID- 30114245
TI  - Correction: Molecular characterization and sensitivity to demethylation inhibitor
      fungicides of Aspergillus fumigatus from orange-based compost.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0200569.].

PMID- 30114246
TI  - Comparison of the dose-response pharmacodynamic profiles of detemir and glargine
      in severely obese patients with type 2 diabetes: A single-blind, randomised cross
      over trial.
AB  - BACKGROUND: Despite their widespread use in this population, data on the
      pharmacodynamic (PD) properties of the insulin analogs detemir and glargine in
      severely obese patients with type 2 diabetes are lacking. METHODS: The primary
      objective of the study was to compare the PD properties of two different doses of
      the basal insulin analogs detemir and glargine in patients with type 2 diabetes
      and a BMI > 35 kg/m2. PD data were derived from euglycemic clamp studies over 30
      hours and each subject was studied for four times after the subcutaneous
      injection of a lower (0.8 U/kg body weight) and higher (1.6 U/kg body weight)
      dose of both detemir and glargine using a single-blind, randomised cross-over
      design. RESULTS: Six male and four female patients with type 2 diabetes and a
      mean BMI of 43.2+/-5.1 kg/m2 (mean age 55.7+/-2 years, mean HbA1c 7.2+/-0.3%)
      completed the study. The total GIRAUC0-30 (mean difference 1224 mg/kg, 95%CI 810
      1637, p = 0.00001), GIRAUC0-24 (mean difference 1040 mg/kg, 95%CI 657-1423; p =
      0.00001), GIRAUC24-30 (mean difference 181 mg/kg, 95%CI 64-298; p = 0.004),
      GIRmax (mean difference 0.93 mg/kg/min, 95%CI 0.22-1.64, p = 0.01) and time to
      GIRmax (+1.9 hours, 95%CI 0.5-3.2; p = 0.009) were higher after the higher doses
      of both insulins, without significant differences between detemir and glargine.
      However, during the last 6 hours of the clamp the GIRAUC24-30 was significantly
      increased with glargine (mean difference 122 mg/kg, 95%CI 6-237, p = 0.043),
      reflecting a more pronounced late glucose lowering effect. CONCLUSIONS: A clear
      dose-response relationship can be demonstrated for both insulin analogs, even at
      very high doses in severely obese patients with type 2 diabetes. Compared to
      detemir, glargine has a more pronounced late glucose lowering effect 24-30 h
      after its injection. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN57547229.

PMID- 30114247
TI  - Deubiquitinase inhibitor PR-619 reduces Smad4 expression and suppresses renal
      fibrosis in mice with unilateral ureteral obstruction.
AB  - Deubiquitinating enzymes (DUBs) remove ubiquitin from their substrates and,
      together with ubiquitin ligases, play an important role in the regulation of
      protein expression. Although transforming growth factor (TGF)-beta1-Smad
      signaling is a central pathway of renal fibrosis, the role of DUBs in the
      expression of TGF-beta receptors and Smads during the development of renal
      fibrosis remains unknown. In this study, we investigated whether PR-619, a pan
      DUB inhibitor, suppresses fibrosis in mice with unilateral ureteral obstruction
      (UUO) and TGF-beta1-stimulated normal rat kidney (NRK)-49F cells, a rat renal
      fibroblast cell line. Either the vehicle (dimethyl sulfoxide) or PR-619 (100 MUg)
      was intraperitoneally administered to mice after UUO induction once a day for 7
      days. Administration of PR-619 attenuated renal fibrosis with downregulation of
      mesenchymal markers, extracellular matrix proteins, matrix metalloproteinases,
      apoptosis, macrophage infiltration, and the TGF-beta1 mRNA level in UUO mice.
      Although type I TGF-beta receptor (TGF-betaRI), Smad2, Smad3, and Smad4 protein
      expression levels were markedly increased in mice with UUO, administration of PR
      619 suppressed only Smad4 expression but not TGF-betaRI, Smad2, or Smad3
      expression. PR-619 also had an inhibitory effect on TGF-beta1-induced alpha
      smooth muscle actin expression and reduced Smad4 levels in NRK-49F cells. Our
      results indicate that PR-619 ameliorates renal fibrosis, which is accompanied by
      the reduction of Smad4 expression.

PMID- 30114248
TI  - The blessing of Dimensionality: Feature Selection outperforms functional
      connectivity-based feature transformation to classify ADHD subjects from EEG
      patterns of phase synchronisation.
AB  - Functional connectivity (FC) characterizes brain activity from a multivariate set
      of N brain signals by means of an NxN matrix A, whose elements estimate the
      dependence within each possible pair of signals. Such matrix can be used as a
      feature vector for (un)supervised subject classification. Yet if N is large, A is
      highly dimensional. Little is known on the effect that different strategies to
      reduce its dimensionality may have on its classification ability. Here, we apply
      different machine learning algorithms to classify 33 children (age [6-14 years])
      into two groups (healthy controls and Attention Deficit Hyperactivity Disorder
      patients) using EEG FC patterns obtained from two phase synchronisation indices.
      We found that the classification is highly successful (around 95%) if the whole
      matrix A is taken into account, and the relevant features are selected using
      machine learning methods. However, if FC algorithms are applied instead to
      transform A into a lower dimensionality matrix, the classification rate drops to
      less than 80%. We conclude that, for the purpose of pattern classification, the
      relevant features should be selected among the elements of A by using appropriate
      machine learning algorithms.

PMID- 30114250
TI  - Stirring the strategic direction of scuba diving marine Citizen Science: A survey
      of active and potential participants.
AB  - Citizen Science (CS) strengthens the relationship between society and science
      through education and engagement, with win-win benefits. Marine Citizen Science
      (MCS) is increasingly popular, thanks to society's growing interest in marine
      environments and marine issues. Scuba diving significantly increases the
      potential of MCS, thanks to the skills and behavioural properties of people who
      participate in the sport. To be able to exploit this potential, however, MCS
      needs to face challenges related to CS, to scuba diving activities and to the
      broader scuba diving industry. In particular, engagement and recruitment of
      potential volunteers, as well as retention of active participants, represent key
      milestones. In order to reach these milestones, information is required on
      current participation levels of scuba divers in MCS, as well as the motivations
      behind participation, and the opinions held by potential participants in MCS.
      This study explored different case studies and methods of data collection to
      provide an overview of actual and potential participation in MCS by the scuba
      diving community. The results show that scuba divers, whether active or potential
      marine citizen scientists, are well disposed towards MCS. Some barriers, however,
      prevent the full participation of scuba divers as marine citizen scientists.
      Certain barriers extend beyond the control of both divers and MCS projects, while
      others, such as limited access to MCS projects and poor feedback after
      participation, can and should be addressed. The recommendations of this research
      provide strategic direction to MCS, so that the broad scuba diving community can
      be successfully integrated into MCS. These recommendations acknowledge the
      important role played by stakeholders in the scuba diving industry, as well as
      professional intermediaries and hired experts.

PMID- 30114249
TI  - Adipokines demonstrate the interacting influence of central obesity with other
      cardiometabolic risk factors of metabolic syndrome in Hong Kong Chinese adults.
AB  - OBJECTIVE: Metabolic syndrome (MetS) or prediabetes is a complex disorder that is
      defined by a clustering of cardiometabolic risk factors, including obesity,
      hypertriglyceridemia, reduced high-density lipoprotein (HDL) cholesterol,
      hypertension, and insulin resistance. Among cardiometabolic risk factors, central
      obesity plays a key role in the development of MetS through alterations in the
      secretion of adipokines and interacts with other MetS risk factors to unfavorably
      influence overall cardiometabolic risk. Obesity has grasped epidemic proportions
      in Asia, which has the highest number of people with diabetes in the world. But,
      the importance of central obesity in the clustering of all four MetS risk factors
      or vice versa in predicting severity of MetS has not yet been investigated in
      Asian population. Therefore, the present study examined the influence of central
      obesity on circulating levels of adipokines through its interaction with the
      clustering of cardiometabolic risk factors of MetS including hyperglycemia,
      hypertriglyceridemia, dyslipidemia and hypertension in Hong Kong Chinese adults.
      SUBJECTS: Blood samples from 83 Hong Kong Chinese adults, who were previously
      screened for MetS according to the guideline of the United States National
      Cholesterol Education Program Expert Panel Adult Treatment Panel III criteria
      were selected. Insulin and adipokines, including visfatin, chemerin, plasminogen
      activator inhibitor-1 (PAI-1), resistin, C-C motif chemokine ligand 2 (CCL-2),
      interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumour
      necrosis factor-alpha (TNF-alpha), leptin and adiponectin were assessed. RESULTS:
      The interacting effect of central obesity with all of the other four MetS risk
      factors increased the proinflammatory status of adipokines (TNF-alpha, leptin)
      and decreased the anti-inflammatory status of adipokine (adiponectin).
      CONCLUSION: Our results indicate that the inflammatory status of MetS may be more
      severe in the presence of central obesity. Adipokines, as biomarkers for
      pathophysiological changes, may help to improve early patient identification and
      to predict MetS-associated morbidity and mortality.

PMID- 30114251
TI  - Rapid, inexpensive, fingerstick, whole-blood, sensitive, specific, point-of-care
      test for anti-Toxoplasma antibodies.

PMID- 30114252
TI  - Surveillance cues do not enhance altruistic behavior among anonymous strangers in
      the field.
AB  - The degree of altruistic behavior among strangers is an evolutionary puzzle. A
      prominent explanation is the evolutionary legacy hypothesis according to which an
      evolved reciprocity-based psychology affects behavior even when reciprocity is
      impossible, i.e., altruistic behavior in such instances is maladaptive. Empirical
      support for this explanation comes from laboratory experiments showing that
      surveillance cues, e.g., photographs of watching eyes, increase altruistic
      behavior. A competing interpretation for this evidence, however, is that the cues
      signal the experimenter's expectations and participants, aware of being
      monitored, intentionally behave more altruistically to boost their reputation.
      Here we report the first results from a field experiment on the topic in which
      participants are unaware they are being monitored and reciprocity is precluded.
      The experiment investigates the impact of surveillance cues on a textbook example
      of altruistic behavior-hand hygiene prior to treating a 'patient'. We find no
      evidence surveillance cues affect hand hygiene, despite using different measures
      of hand-hygiene quality and cues that have been previously shown to be effective.
      We argue that surveillance cues may have an effect only when participants have
      reasons to believe they are actually monitored. Thus they cannot support claims
      altruistic behavior between strangers is maladaptive.

PMID- 30114254
TI  - Would you like to leave Beijing, Shanghai, or Shenzhen? An empirical analysis of
      migration effect in China.
AB  - This study aims to estimate the migration effect of the overall samples and
      different flowing scales for the floating population from the perspective of
      personal wages. Although we used both the OLS and PSM methods to estimate the
      migration effect, we found that the PSM method was preferred in the study of
      migration as a result of the selection bias. The empirical results show that
      there is a significant difference in wage before and after migration. In fact,
      migration increased wages by 15.18% to 23.63% overall. Additionally, wages were
      increased by 44.96% to 59.20%, 23.06% to 26.18%, and 10.89% to 15.08%
      respectively for these three migration patterns: flowing into the three largest
      megacities, inter-provincial migration, and inter-city migration within a
      province, but for this pattern of inter-district migration within a city, the
      migration effect is not significant. We concluded that the floating population
      removing policies of the largest megacities maybe are effective because of the
      administrative power of their government. On the other hand, for these policies
      of non-largest megacities to attract labor and local employment and local
      urbanization near the floating population's place of origin, they were not
      effective enough as a result of the lack of significant migration effect in these
      cities.

PMID- 30114253
TI  - The VP1 unique region of human parvovirus B19 and human bocavirus induce lung
      injury in naive Balb/c mice.
AB  - Both human parvovirus B19 (B19V) and human bocavirus (HBoV) are known to be
      important human pathogens of the Parvoviridae family. Our earlier investigation
      demonstrated that both B19V-VP1u and HBoV-VP1u have a significantly disruptive
      effect on tight junctions (TJs) in A549 cells, implying the essential role of
      parvovirus in airway infection and lung injury. However, no direct evidence that
      B19V-VP1u and HBoV-VP1u induce lung injury exists. The present study further
      investigates the induction of lung injury by B19V-VP1u and HBoV-VP1u in naive
      Balb/c mice following subcutaneous injection of PBS, recombinant B19V-VP1u or
      HBoV-VP1u. The experimental results reveal significantly increased activity,
      protein expression and ratio of matrix metalloproteinase-9 (MMP-9) to MMP-2 in
      Balb/c mice that received B19V-VP1u or HBoV-VP1u compared to those that received
      PBS. Significantly higher levels of inflammatory cytokines, including IL-6 and IL
      1beta, and greater lymphocyte infiltration in lung tissue sections were detected
      in mice that received B19V-VP1u or HBoV-VP1u. Additionally, significantly
      increased levels of phosphorylated p65 (NF-kappaB) and MAPK signaling proteins
      were observed in lung tissue of mice that received B19V-VP1u or HBoV-VP1u
      compared to those of mice that received PBS. These findings demonstrate for the
      first time that B19V-VP1u and HBoV-VP1u proteins induce lung inflammatory
      reactions through p65 (NF-kappaB) and MAPK signaling.

PMID- 30114255
TI  - Correction: Weight estimation for children aged 6 to 59 months in limited
      resource settings: A proposal for a tape using height and mid-upper arm
      circumference.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0197769.].

PMID- 30114256
TI  - Probing hyper-negatively supercoiled mini-circles with nucleases and DNA binding
      proteins.
AB  - It is well accepted that the introduction of negative supercoils locally unwinds
      the DNA double helix, influencing thus the activity of proteins. Despite the use
      of recent methods of molecular dynamics simulations to model the DNA supercoiling
      induced DNA deformation, the precise extent and location of unpaired bases
      induced by the negative supercoiling have never been investigated at the
      nucleotide level. Our goals in this study were to use radiolabeled double
      stranded DNA mini-circles (dsMCs) to locate the unpaired bases on dsMCs whose
      topology ranged from relaxed to hyper-negatively supercoiled states, and to
      characterize the binding of proteins involved in the DNA metabolism. Our results
      show that the Nuclease SI is nearly ten times more active on hyper-negatively
      supercoiled than relaxed DNA. The structural changes responsible for this
      stimulation of activity were mapped for the first time with a base pair
      resolution and shown to be subtle and distributed along the entire sequence. As
      divalent cations modify the DNA topology, our binding studies were conducted with
      or without magnesium. Without magnesium, the dsMCs topoisomers mostly differ by
      their twist. Under these conditions, the Escherichia coli topoisomerase I weakly
      binds relaxed dsMCs and exhibits a stronger binding on negatively and hyper
      negatively supercoiled dsMCs than relaxed dsMCs, with no significant difference
      in the binding activity among the supercoiled topoisomers. For the human
      replication protein A (hRPA), the more negatively supercoiled is the DNA, the
      better the binding, illustrating the twist-dependent binding activity for this
      protein. The presence of magnesium permits the dsMCs to writhe upon introduction
      of negative supercoiling and greatly modifies the binding properties of the hRPA
      and Escherichia coli SSB on dsMCs, indicating a magnesium-dependent DNA binding
      behavior. Finally, our experiments that probe the topology of the DNA in the hRPA
      dsMC complexes show that naked and hRPA-bound dsMCs have the same topology.

PMID- 30114257
TI  - Intensive care nurses' knowledge and practice on endotracheal suctioning of the
      intubated patient: A quantitative cross-sectional observational study.
AB  - INTRODUCTION: Endotracheal suction (ETS) is a common invasive procedure which is
      done to keep the airways patent by mechanically removing accumulated pulmonary
      secretions to all in patients with artificial airways. Many life-threatening
      complications can occur when the procedure is not performed correctly. Although
      the evidence-based recommendations regarding ETS are available, many of these
      have not been observed in nurse's clinical practice. We assessed the intensive
      care nurses' knowledge and practice of ETS to intubated patients in selected
      hospitals in Dar es Salaam, Tanzania. METHODOLOGY: A descriptive cross-sectional
      study design involving 103 Intensive Care Unit (ICU) nurses in Dar es Salaam city
      was conducted in 2014. Data were analyzed using SPSS version 20 where descriptive
      statistics were employed to interpret data. RESULTS: Majority of ICU nurses
      (69.9%) knew the indication for the procedure, (77.7%) knew the action to be
      taken in case of abrupt change in the ECG monitor; however, 80.6% demonstrated
      undesirable overall knowledge on ETS evidence-based recommendations. Nurses with
      ICU training (57.3%) significantly demonstrated higher knowledge of ETS than non
      trained nurses (P<0.005), while all other factors had no influence. CONCLUSIONS
      AND RECOMMENDATIONS: Majority of ICU nurses do not have desirable knowledge and
      skills of ETS, and are currently not following current ETS recommendations. This
      study has shown that training on ICU skills have positive influence to
      recommended ETS knowledge. We recommend ICU training, provision of clinical
      guidelines and adequate support to nurses employed in ICUs. Also, further studies
      using analytical approach to identify other factors beyond the scope of this
      study and testing the best approach in fostering adherence to ETS evidence-based
      recommendations are crucial.

PMID- 30114258
TI  - In vitro assessment of the influence of intravenous extension set materials on
      insulin aspart drug delivery.
AB  - Insulin is a frequently prescribed drug in hospitals and is usually administered
      by syringe pumps with an extension line which can be made of various materials.
      Two insulin solutions were studied: an insulin analogue, Novorapid(r) which
      contains insulin aspart and two phenolic preservatives (e.g. phenol and
      metacresol) and Umuline rapide(r) with human insulin and metacresol as
      preservative. Some studies have indicated interactions between insulin, polyvinyl
      chloride (PVC) and polyethylene (PE). The aim of this work was to study such
      interactions between Novorapid(r) or Umuline rapide(r) and infusion extension
      line materials (PVC, PE and coextruded (PE/PVC)). Insulin solution at 1 IU/mL was
      infused at 2 mL/h over 24 hours with 16 different extension lines (8 in PVC, 3 in
      PE and 5 in PE/PVC). Ultra-Fast Liquid Chromatography with diode array detection
      (UFLC-DAD) was performed to quantify insulin (human and aspart) and preservatives
      (metacresol and phenol). Limited human insulin sorption was observed thirty
      minutes after the onset of infusion: 24.3 +/- 12.9%, 3.1 +/- 1.6% and 18.6 +/-
      10.0% for PVC, PE and PE/PVC respectively. With insulin aspart, sorption of about
      5% was observed at the onset of infusion for all materials. However, there were
      interactions between phenol and especially metacresol with PVC, but no
      interactions with PE and PE/PVC. This study shows that insulin interacts with
      PVC, PE and PE/PVC at the onset of infusion. It also demonstrates that insulin
      preservatives interact with PVC, which may result in problems of insulin
      conservation and conformation. Some more studies are required to understand the
      clinical impact of the latter during infusion.

PMID- 30114259
TI  - Distribution of item responses and total item scores for the Center for
      Epidemiologic Studies Depression Scale (CES-D): Data from the Irish Longitudinal
      Study on Ageing (TILDA).
AB  - BACKGROUND: Previous studies have shown that item responses and total scores on
      depression screening scales follow characteristic distribution patterns in the
      United States and Japanese general populations. However, the degree to which
      these findings, especially in terms of item responses, can be generalized to a
      European population is unknown. Thus, we analyzed the item responses and total
      score distribution for the Center for Epidemiologic Studies Depression Scale (CES
      D) in a representative Irish cohort from a large, recent study-the Irish
      Longitudinal Study on Ageing (TILDA). METHODS: We used CES-D data from the 2009
      2011 TILDA (8504 individuals). Responses for the 16 depressive symptoms included
      "rarely," "some of the time," "occasionally," and "all of the time." Item
      response patterns and total score distribution across these 16 depressive symptom
      items were examined using graphical analyses and exponential regression modeling.
      RESULTS: Lines for item responses followed the same pattern across the 16 items.
      These lines were characterized by intersections in the vicinity of a single point
      between "rarely" and "some of the time" and parallel patterns from "some of the
      time" to "all of the time" on a log-normal scale. Total scores for the 16 items
      exhibited an exponential pattern, except for at the lower end of the
      distribution. CONCLUSIONS: The present findings suggest that item responses and
      total scores on depression screening scales among the general population follow
      the same characteristic patterns across populations from multiple nations.

PMID- 30114260
TI  - Immobility in the sedentary plant-parasitic nematode H. glycines is associated
      with remodeling of neuromuscular tissue.
AB  - The sedentary plant-parasitic nematodes are considered among the most
      economically damaging pathogens of plants. Following infection and the
      establishment of a feeding site, sedentary nematodes become immobile. Loss of
      mobility is reversed in adult males while females never regain mobility. The
      structural basis for this change in mobility is unknown. We used a combination of
      light and transmission electron microscopy to demonstrate cell-specific muscle
      atrophy and sex-specific renewal of neuromuscular tissue in the sedentary
      nematode Heterodera glycines. We found that both females and males undergo body
      wall muscle atrophy and loss of attachment to the underlying cuticle during
      immobile developmental stages. Male H. glycines undergo somatic muscle renewal
      prior to molting into a mobile adult. In addition, we found developmental changes
      to the organization and number of motor neurons in the ventral nerve cord
      correlated with changes in mobility. To further examine neuronal changes
      associated with immobility, we used a combination of immunohistochemistry and
      molecular biology to characterize the GABAergic nervous system of H. glycines
      during mobile and immobile stages. We cloned and confirmed the function of the
      putative H. glycines GABA synthesis-encoding gene hg-unc-25 using heterologous
      rescue in C. elegans. We found a reduction in gene expression of hg-unc-25 as
      well as a reduction in the number of GABA-immunoreactive neurons during immobile
      developmental stages. Finally, we found evidence of similar muscle atrophy in the
      phylogenetically diverged plant-parasitic nematode Meloidogyne incognita.
      Together, our data demonstrate remodeling of neuromuscular structure and function
      during sedentary plant-parasitic nematode development.

PMID- 30114261
TI  - The activation of the oxidative stress response transcription factor SKN-1 in
      Caenorhabditis elegans by mitis group streptococci.
AB  - The mitis group, a member of the genetically diverse viridans group streptococci,
      predominately colonizes the human oropharynx. This group has been shown to cause
      a wide range of infectious complications in humans, including bacteremia in
      patients with neutropenia, orbital cellulitis and infective endocarditis.
      Hydrogen peroxide (H2O2) has been identified as a virulence factor produced by
      this group of streptococci. More importantly, it has been shown that
      Streptococcus oralis and S. mitis induce epithelial cell and macrophage death via
      the production of H2O2. Previously, H2O2 mediated killing was observed in the
      nematode Caenorhabditis elegans in response to S. oralis and S. mitis. The
      genetically tractable model organism C. elegans is an excellent system to study
      mechanisms of pathogenicity and stress responses. Using this model, we observed
      rapid H2O2 mediated killing of the worms by S. gordonii in addition to S. mitis
      and S. oralis. Furthermore, we observed colonization of the intestine of the
      worms when exposed to S. gordonii suggesting the involvement of an infection-like
      process. In response to the H2O2 produced by the mitis group, we demonstrate the
      oxidative stress response is activated in the worms. The oxidative stress
      response transcription factor SKN-1 is required for the survival of the worms and
      provides protection against H2O2 produced by S. gordonii. We show during
      infection, H2O2 is required for the activation of SKN-1 and is mediated via the
      p38-MAPK pathway. The activation of the p38 signaling pathway in the presence of
      S. gordonii is not mediated by the endoplasmic reticulum (ER) transmembrane
      protein kinase IRE-1. However, IRE-1 is required for the survival of worms in
      response to S. gordonii. These finding suggests a parallel pathway senses H2O2
      produced by the mitis group and activates the phosphorylation of p38.
      Additionally, the unfolded protein response plays an important role during
      infection.

PMID- 30114262
TI  - High-sensitivity C-reactive protein in heart failure with preserved ejection
      fraction.
AB  - BACKGROUND: Microvascular inflammation may contribute to the pathogenesis of both
      heart failure with preserved ejection fraction (HFpEF) and pulmonary hypertension
      (PH). We investigated whether the inflammation biomarker C-reactive protein (CRP)
      was associated with clinical characteristics, disease severity or PH in HFpEF.
      METHODS: Patients in the Phosphodiesterase-5 Inhibition to Improve Clinical
      Status and Exercise Capacity in Diastolic Heart failure (RELAX) trial had
      baseline high-sensitivity CRP levels measured (n = 214). Clinical
      characteristics, exercise performance, echocardiographic variables and biomarkers
      of neurohumoral activation, fibrosis and myocardial necrosis were assessed.
      Patients with normal (<=3mg/L) versus high (>3mg/L) CRP levels were compared.
      RESULTS: The median CRP level was 3.69mg/L. CRP was elevated in 57% of patients.
      High CRP levels were associated with younger age, higher body mass index (BMI),
      chronic obstructive pulmonary disease (COPD), lower peak oxygen consumption and
      higher endothelin-1 and aldosterone levels. CRP increased progressively with the
      number of comorbidities (0.7mg/L per increment in comorbidity number, P = 0.02).
      Adjusting for age, BMI and statin use, high CRP levels were additionally
      associated with atrial fibrillation, right ventricular dysfunction, and higher N
      terminal pro-B-type natriuretic peptide levels (P<0.05 for all). CRP was not
      associated with PH or left ventricular function. CRP did not identify responders
      to sildenafil(P-value for interaction 0.13). CONCLUSIONS: In HFpEF, high CRP is
      associated with greater comorbidity burden and some markers of disease severity
      but CRP was normal in 40% of patients. These findings support the presence of
      comorbidity-driven systemic inflammation in HFpEF but also the need to study
      other biomarkers which may better reflect the presence of systemic inflammation.

PMID- 30114264
TI  - Perceived neighbourhood affluence, mental health and wellbeing influence
      judgements of threat and trust on our streets: An urban walking study.
AB  - This study aimed to understand how people respond to different urban
      neighbourhoods. We explored whether participants' mental health and wellbeing,
      judgements of resident wealth, family SES and sentiments reflected in
      descriptions of place features predicted in situ sense of threat and trust. Forty
      six student participants walked in groups through 2 urban neighbourhoods,
      separated by a park, in the North West of England, noting responses at pre
      determined stops. Significant differences existed in participants' sense of trust
      and threat between the 2 neighbourhoods along with differences in perceived
      resident wealth and sentiments expressed. Participants' levels of persecutory
      ideas and their sense of residents' wealth predicted in situ trust in both
      neighbourhoods while level of personal resilience predicted the extent of threat
      felt in the more deprived neighbourhood. Demonstrating the value of the method,
      these findings have implications for the governance of urban neighbourhoods
      whereby obvious cues signalling a harsh environment need to be minimised to
      create more positive psychological responses to places.

PMID- 30114265
TI  - D-Track-A semi-automatic 3D video-tracking technique to analyse movements and
      routines of aquatic animals with application to captive dolphins.
AB  - Scoring and tracking animal movements manually is a time consuming and subjective
      process, susceptible to errors due to fatigue. Automated and semi-automated video
      based tracking methods have been developed to overcome the errors and biases of
      manual analyses. In this manuscript we present D-Track, an open-source semi
      automatic tracking system able to quantify the 3D trajectories of dolphins, non
      invasively, in the water. This software produces a three-dimensional
      reconstruction of the pool and tracks the animal at different depths, using
      standard cameras. D-Track allows the determination of spatial preferences of the
      animals, their speed and its variations, and the identification of behavioural
      routines. We tested the system with two captive dolphins during different periods
      of the day. Both animals spent around 85% of the time at the surface of the Deep
      Area of their pool (5-meters depth). Both dolphins showed a stable average speed
      throughout 31 sessions, with slow speeds predominant (maximum 1.7 ms-1). Circular
      swimming was highly variable, with significant differences in the size and
      duration of the "circles", between animals, within-animals and across sessions.
      The D-Track system is a novel tool to study the behaviour of aquatic animals, and
      it represents a convenient and inexpensive solution for laboratories and marine
      parks to monitor the preferences and routines of their animals.

PMID- 30114263
TI  - Glial responses during epileptogenesis in Mus musculus point to potential
      therapeutic targets.
AB  - The Mesio-Temporal Lobe Epilepsy syndrome is the most common form of intractable
      epilepsy. It is characterized by recurrence of focal seizures and is often
      associated with hippocampal sclerosis and drug resistance. We aimed to
      characterize the molecular changes occurring during the initial stages of
      epileptogenesis in search of new therapeutic targets for Mesio-Temporal Lobe
      Epilepsy. We used a mouse model obtained by intra-hippocampal microinjection of
      kainate and performed hippocampal whole genome expression analysis at 6h, 12h and
      24h post-injection, followed by multilevel bioinformatics analysis. We report
      significant changes in immune and inflammatory responses, neuronal network
      reorganization processes and glial functions, predominantly initiated during
      status epilepticus at 12h and persistent after the end of status epilepticus at
      24h post-kainate. Upstream regulator analysis highlighted Cyba, Cybb and Vim as
      central regulators of multiple overexpressed genes implicated in glial responses
      at 24h. In silico microRNA analysis indicated that miR-9, miR-19b, miR-129, and
      miR-223 may regulate the expression of glial-associated genes at 24h. Our data
      support the hypothesis that glial-mediated inflammatory response holds a key role
      during epileptogenesis, and that microglial cells may participate in the initial
      process of epileptogenesis through increased ROS production via the NOX complex.

PMID- 30114266
TI  - Cross-country information transmissions and the role of commodity markets: A
      multichannel Markov switching approach.
AB  - This paper examines the interrelationships among 9 advanced economies using a
      novel multichannel approach to investigate, beyond the usual causal
      relationships, the time-varying dimension of the channels conveying causal
      relationships. The model is derived from the well-known Markov Switching setting
      and account for systems described by multiple variables. A Markov switching
      causality measure is adapted to account for information transmissions between
      distinct multivariate systems. Each country is described by 5 different
      fundamental variables reflecting its state. Our multichannel causality measure is
      then applied on these sets of time series to determine, over time, the main
      channels through which the information is transmitted between the different
      countries. In a second step, we investigate the relationships existing between
      these countries and the commodity markets and look at the possible use of the
      commodity markets as an indirect channel of information transmission between
      countries.

PMID- 30114267
TI  - Genetic homogeneity of North-African goats.
AB  - North Africa represents a rich and early reservoir of goat genetic diversity,
      from which the main African breeds have been derived. In this study, the genetic
      diversity of four indigenous Algerian goat breeds (i.e., Arabia, Makatia,
      M'Zabite and Kabyle, with n = 12 for each breed) has been investigated for the
      first time by genome-wide SNP genotyping; moreover in a broader context, genetic
      structuration of Algerian and Moroccan goats was explored (via FST, MDS,
      STRUCTURE, FineSTRUCTURE, BAPS, sPCA and DAPC analyses). At national level, the
      study revealed high level of genetic diversity and a significant phenomenon of
      admixture affecting all the Algerian breeds. At broader scale, clear global
      genetic homogeneity appeared considering both Algerian and Moroccan stocks.
      Indeed, genetic structuration was almost nonexistent among Arabia (from Algeria),
      Draa, Black and Nord (from Morocco), while the ancestral Kabyle and M'Zabite
      breeds, reared by Berber peoples, showed genetic distinctness. The study
      highlighted the threat to the Maghrebin stock, probably induced by unsupervised
      cross-breeding practices which have intensified in recent centuries. Moreover, it
      underlined the necessity to deepen our understanding of the genetic resources
      represented by the resilient North-African goat stock.

PMID- 30114268
TI  - Internuclear diffusion of histone H1 within cellular compartments of Aspergillus
      nidulans.
AB  - Histone H1 is an evolutionarily conserved linker histone protein that functions
      in arranging and stabilizing chromatin structure and is frequently fused to a
      fluorescent protein to track nuclei in live cells. In time-lapse analyses, we
      observed stochastic exchange of photoactivated Dendra2-histone H1 protein between
      nuclei within the same cellular compartment. We also observed exchange of
      histones between genetically distinct nuclei in a heterokaryon derived from
      fusion of strains carrying histone H1-RFP or H1-GFP. Subsequent analysis of the
      resulting uninucleate conidia containing both RFP- and GFP-labeled histone H1
      proteins showed only parental genotypes, ruling out genetic recombination and
      diploidization. These data together suggest that the linker histone H1 protein
      can diffuse between non-daughter nuclei in the filamentous fungus Aspergillus
      nidulans.

PMID- 30114269
TI  - Associations between activity patterns and cardio-metabolic risk factors in
      children and adolescents: A systematic review.
AB  - INTRODUCTION: Total volumes of physical activity and sedentary behaviour have
      been associated with cardio-metabolic risk profiles; however, little research has
      examined whether patterns of activity (e.g., prolonged bouts, frequency of breaks
      in sitting) impact cardio-metabolic risk. The aim of this review was to
      synthesise the evidence concerning associations between activity patterns and
      cardio-metabolic risk factors in children and adolescents aged 5-19 years.
      MATERIALS AND METHODS: A systematic search of seven databases was completed in
      October 2017. Included studies were required to report associations between
      objectively-measured activity patterns and cardio-metabolic risk factors in
      children and/or adolescents, and be published between 1980 and 2017. At least two
      researchers independently screened each study, extracted data, and undertook risk
      of bias assessments. RESULTS: From the 15,947 articles identified, 29 were
      included in this review. Twenty-four studies were observational (cross-sectional
      and/or longitudinal); five were experimental. Ten studies examined physical
      activity patterns, whilst 19 studies examined sedentary patterns. Only one study
      examined both physical activity and sedentary time patterns. Considerable
      variation in definitions of activity patterns made it impossible to identify
      which activity patterns were most beneficial to children's and adolescents'
      cardio-metabolic health. However, potential insights and current research gaps
      were identified. DISCUSSION AND CONCLUSION: A consensus on how to define activity
      patterns is needed in order to determine which activity patterns are associated
      with children's and adolescents' cardio-metabolic risk. This will inform future
      research on the impact of activity patterns on children's and adolescents' short-
      and longer-term health.

PMID- 30114270
TI  - In vivo distribution of U87MG cells injected into the lateral ventricle of rats
      with spinal cord injury.
AB  - Stem cells could be the next generation therapeutic option for neurodegenerative
      diseases including spinal cord injury (SCI). However, several critical factors
      such as delivery method should be determined before their clinical applications.
      Previously, we have demonstrated that lateral ventricle (LV) injection as
      preclinical simulation could be used for intrathecal administration in clinical
      trials using rodent animal models. In this study, we further analyzed in vivo
      distribution of cells that were injected into LVs of rats with SCI at thoracic
      level using in vivo imaging techniques. When 5 * 106 U87MG cells labelled with
      fluorescent magnetic nanoparticle (FMNP-labelled U87MG) were administrated into
      LVs at 7 days after SCI, FMNP-labelled U87MG cells were observed in all regions
      of the spinal cord at 24 hours after the injection. Compared to water-soluble
      Cy5.5 fluorescent dye or rats without SCI, in vivo distribution pattern of FMNP
      labelled U87MG cells was not different, although migration to the spinal cord was
      significantly reduced in both Cy5.5 fluorescent dye and FMNP-labelled U87MG cells
      caused by the injury. The presence of FMNP-labelled U87MG cells in the spinal
      cord was confirmed by quantitative PCR for human specific sequence and
      immunohistochemistry staining using antibody against human specific antigen.
      These data indicate that LV injection could recapitulate intrathecal
      administration of stem cells for SCI patients. Results of this study might be
      applied further to the planning of optimal preclinical and clinical trials of
      stem cell therapeutics for SCI.

PMID- 30114271
TI  - Effect of the screw type (S2-alar-iliac and iliac), screw length, and screw head
      angle on the risk of screw and adjacent bone failures after a spinopelvic
      fixation technique: A finite element analysis.
AB  - PURPOSE: Spinopelvic fixations involving the S2-alar-iliac (S2AI) and iliac
      screws are commonly used in various spinal fusion surgeries. This study aimed to
      compare the biomechanical characteristics, specifically the risk of screw and
      adjacent bone failures of S2AI screw fixation with those of iliac screw fixation
      using a finite element analysis (FEA). METHODS: A three-dimensional finite
      element (FE) model of a healthy spinopelvis was generated. The pedicle screws
      were placed on the L3-S1 with three different lengths of the S2AI and iliac
      screws (60 mm, 75 mm, and 90 mm). In particular, two types of the S2AI screw, 15
      degrees - and 30 degrees -angled polyaxial screw, were adopted. Physiological
      loads, such as a combination of compression, torsion, and flexion/extension
      loads, were applied to the spinopelvic FE model, and the stress distribution as
      well as the maximum von Mises equivalent stress values were calculated. RESULTS:
      For the iliac screw, the highest stress on the screw was observed with the 75-mm
      screw, rather than the 60-mm screw. The bones around the iliac screw indicated
      that the maximum equivalent stress decreased as the screw length increased. For
      the S2AI screw, the lowest stress was observed in the 90-mm screw length with a
      30 degrees  head angle. The bones around the S2AI screw indicated that the lowest
      stress was observed in the 90-mm screw length and a 15 degrees  head angle.
      CONCLUSIONS: It was found that the S2AI screw, rather than the iliac screw,
      reduced the risk of implant failure for the spinopelvic fixation technique, and
      the 90-mm screw length with a 15 degrees  head angle for the S2AI screw could be
      biomechanically advantageous.

PMID- 30114272
TI  - The ethics conundrum in Recall by Genotype (RbG) research: Perspectives from
      birth cohort participants.
AB  - PURPOSE: Recall by genotype (RbG) research recruits on the basis of genetic
      variation. Increased use of this approach presents an ethical conundrum for
      cohort studies/biobanks: whether to inform individuals of their genetic
      information and deviate from standard practice of non-disclosure of results, or
      mask this information at the level of the individual participant. This paper
      examines the perspectives of research study participants on RbG research.
      METHODS: Fifty-three semi-structured interviews were conducted with young adult
      participants of the Avon Longitudinal Study of Parents and Children (ALSPAC).
      Topics included understandings of RbG research, expectations around recruitment
      and communication of research findings. RESULTS: Participants uniformly expressed
      a deep trust and faith in ALSPAC and considered themselves part of the ALSPAC
      team. Such perspectives, alongside a limited knowledge of genetics and modest
      interest in reported research outcomes, meant few participants reported immediate
      concerns about being recruited by genotype. CONCLUSION: Our findings highlight
      the responsibility and duty of care on RbG researchers, and longitudinal studies
      more generally, and the importance of solidarity, reciprocity and co-production
      in study-participant relations. As such, we consider existing recommendations for
      conducting RbG research in longitudinal studies in light of our results and speak
      to recent changes in the approach used by ALSPAC.

PMID- 30114273
TI  - Characterization and expression of a long neuropeptide F (NPF) receptor in the
      Chagas disease vector Rhodnius prolixus.
AB  - In this study, a long neuropeptide F receptor of the blood-feeding hemipteran,
      Rhodnius prolixus (RhoprNPFR) has been cloned and characterized. Approximately
      70% of the RhoprNPFR deduced protein sequence is identical to that of other
      hemipteran NPFRs. RhoprNPFR has seven highly-conserved transmembrane domains, two
      cysteine residues in the 2nd and 3rd extracellular loops that likely form a
      disulfide bond integral for maintaining the structure of the receptor, and a
      conserved DRY motif after the third transmembrane domain. All of these
      characteristics are typical of class A rhodopsin-like GPCRs. The receptor
      transcript is predominantly expressed in the central nervous system (CNS) and gut
      of both fifth instar and adult R. prolixus. Using fluorescent in situ
      hybridization (FISH), we identified six bilaterally-paired large median
      neurosecretory cells (approximately 30MUm in diameter) in the brain that express
      the RhoprNPFR mRNA transcript. We also found RhoprNPFR transcript expression in
      endocrine cells in the anterior midgut of fifth instars, as well as in putative
      pre-follicular cells present in the germarium and between developing oocytes, and
      in the nutritive cord. These results suggest that RhoprNPFR may play a role
      within the CNS, and in digestion and possibly egg production and/or egg
      development in R. prolixus.

PMID- 30114274
TI  - Factors associated with willingness to enter long-term care facilities among
      older adults in Chengdu, China.
AB  - OBJECTIVE: To describe Chinese older adults' willingness to enter long-term care
      facilities and to examine individual factors associated with the willingness of
      using this growing model of long-term care in China. METHODS: A cross-sectional
      study involving a random sample of 670 adults aged 60+ in the Hezuo community in
      Chengdu, China in 2016. Respondents were interviewed by trained staff on socio
      demographics, health status, quality of life, social support, and willingness to
      enter long-term care facilities. RESULTS: Only 11.9% of the respondents were
      willing to enter long-term care facilities for meeting their medical and social
      service needs. Multivariable logistic regression analysis showed that willingness
      to enter long-term care facilities was associated with higher household income
      (OR = 4.55, 95% CI:1.72-12.00), insurance of Urban Resident Basic Medical
      Insurance (OR = 4.80, 95% CI:1.17-19.67) and unemployment (OR = 0.48, 95% CI:0.24
      0.99). Among those who were willing to enter long-term care facilities, an
      overwhelming majority (81.2%) would prefer going to a facility within 30-minute
      walking distance from their current residence, 82.5% indicated the need of
      nursing care, and 90.0% expected a partnership between the long-term care
      facility and a large hospital. CONCLUSIONS: A minority of older Chinese were
      willing to receive long-term care delivered at a facility within walking distance
      from their current residence. Recent policy aimed at increasing the supply of
      long-term care facilities may not be consistent with consumer preference for home
      and community-based care. Balancing investment between home and community-based
      care, and establishing long-term care insurance remain the top priorities for
      long-term care research and policy development in China.

PMID- 30114276
TI  - Responses of aerial insectivorous bats to local and landscape-level features of
      coffee agroforestry systems in Western Ghats, India.
AB  - Shade coffee has shown great promise in providing crucial habitats for
      biodiversity outside formal protected areas. Insectivorous bats have been
      understudied in coffee, although they may provide pest control services. We
      investigated the influence of local and landscape-level features of coffee farms
      on aerial insectivorous bats in Chikmagalur district in the Western Ghats
      biodiversity hotspot, India. Bats were monitored in 20 farm sites using
      ultrasound detectors, and the response of bat species richness and activity to
      changes in tree density, proportion of built-up area in the neighborhood, and
      distance of farm from forest areas quantified. We examined if models built to
      explain the species richness and activity could also predict them in nine
      additional sites. We detected nine phonic types/species in the study area. The
      quantified predictors had no effect on assemblage-level species richness and
      activity of bats. Responses of edge-space and cluttered-space forager guilds
      mirrored those of the overall assemblage, but some species vulnerable to forest
      conversion like Rhinolophus beddomei were detected rarely. Best models explained
      up to 20% and 15% variation in assemblage-level species richness and activity
      respectively, and were poor predictors of both response variables. We conclude
      that coffee farms in our study area offer an important commuting space for
      insectivorous bats across a gradient of shade management. Further research should
      include species-specific responses to management decisions for at-risk species
      and quantification of ecosystem services like natural pest control to inform
      biodiversity conservation initiatives in the Western Ghats coffee landscapes.

PMID- 30114275
TI  - Genetic structure of the grey side-gilled sea slug (Pleurobranchaea maculata) in
      coastal waters of New Zealand.
AB  - Pleurobranchaea maculata is a rarely studied species of the Heterobranchia found
      throughout the south and western Pacific-and recently recorded in Argentina-whose
      population genetic structure is unknown. Interest in the species was sparked in
      New Zealand following a series of dog deaths caused by ingestions of slugs
      containing high levels of the neurotoxin tetrodotoxin. Here we describe the
      genetic structure and demographic history of P. maculata populations from five
      principle locations in New Zealand based on extensive analyses of 12
      microsatellite loci and the COI and CytB regions of mitochondrial DNA (mtDNA).
      Microsatellite data showed significant differentiation between northern and
      southern populations with population structure being associated with previously
      described regional variations in tetrodotoxin concentrations. However, mtDNA
      sequence data did not support such structure, revealing a star-shaped haplotype
      network with estimates of expansion time suggesting a population expansion in the
      Pleistocene era. Inclusion of publicly available mtDNA sequence sea slugs from
      Argentina did not alter the star-shaped network. We interpret our data as
      indicative of a single founding population that fragmented following geographical
      changes that brought about the present day north-south divide in New Zealand
      waters. Lack of evidence of cryptic species supports data indicating that
      differences in toxicity of individuals among regions are a consequence of
      differences in diet.

PMID- 30114277
TI  - The United Kingdom National Neonatal Research Database: A validation study.
AB  - BACKGROUND: The National Neonatal Research Database (NNRD) is a rich repository
      of pre-defined clinical data extracted at regular intervals from point-of-care,
      clinician-entered electronic patient records on all admissions to National Health
      Service neonatal units in England, Wales, and Scotland. We describe population
      coverage for England and assess data completeness and accuracy. METHODS: We
      determined population coverage of the NNRD in 2008-2014 through comparison with
      data on live births in England from the Office for National Statistics. We
      determined the completeness of seven data items on the NNRD. We assessed the
      accuracy of 44 data items (16 patient characteristics, 17 processes, 11 clinical
      outcomes) for infants enrolled in the multi-centre randomised controlled trial,
      Probiotics in Preterm Study (PiPs). We compared NNRD to PiPs data, the gold
      standard, and calculated discordancy rates using predefined criteria, and
      sensitivity, specificity and positive predictive values (PPV) of binary outcomes.
      RESULTS: The NNRD holds complete population data for England for infants born
      alive from 25+0 to 31+6 (completed weeks) of gestation; and 70% and 90% for those
      born at 23 and 24 weeks respectively. Completeness of patient characteristics was
      over 90%. Data were linked for 2257 episodes of care received by 1258 of the 1310
      babies recruited to PiPs. Discordancy rates were <5% for 13/16 patient
      characteristics (exceptions: mode of delivery 8.7%; maternal ethnicity 10.2%,
      Lower layer Super Output Area 16.5%); <5% for 9/16 processes (exceptions: medical
      treatment for Patent ductus arteriosus 6.1%, high-dependency days 10.2%, central
      line days 11.2%, type of first milk 22.3%; and during first 14 days, summary of
      types of milk 13.8%; number of days of antibiotics 9.0%; whether antacid given
      5.1%); and <5% for 10/11 clinical outcomes (exception: Bronchopulmonary
      dysplasia, defined as oxygen dependency at 36 weeks postmenstrual age 3.3%). The
      specificity of NNRD data was >85% for all outcomes; sensitivity ranged from 50
      100%; PPV ranged from 58.8 (95% CI 40.8-75.4%) for porencephalic cyst to 99.7
      (95% CI 99.2, 99.9%) for survival to discharge. CONCLUSIONS: The completeness and
      quality of data held in the NNRD is high, providing assurance in relation to use
      for multiple purposes, including national audit, health service evaluations,
      quality improvement, and research.

PMID- 30114278
TI  - PPARgamma is reduced in the airways of non-CF bronchiectasis subjects and is
      inversely correlated with the presence of Pseudomonas aeruginosa.
AB  - BACKGROUND: Chronic airway inflammation in conditions such as cystic fibrosis
      (CF) and non-CF bronchiectasis is characterised by a predominant neutrophilic
      inflammatory response, commonly due to the presence of pathogenic bacteria such
      as Pseudomonas aeruginosa. We hypothesised that down-regulation of the anti
      inflammatory nuclear transcription regulator peroxisome proliferator-activated
      receptor gamma (PPARgamma in non-CF bronchiectasis subjects may explain why this
      exuberant neutrophilic inflammation is able to persist unchecked in the inflamed
      airway. METHODS: PPARgamma gene expression was assessed in bronchoalveolar lavage
      fluid (BAL) of 35 macrolide naive non-CF bronchiectasis subjects and compared
      with that in 20 healthy controls. Human RNA was extracted from pelleted BAL and
      PPARgamma expression was determined by reverse-transcription quantitative PCR.
      Bacterial DNA was extracted from paired induced sputum and total bacterial load
      was determined by 16S rRNA qPCR. Quantification of individual bacterial species
      was achieved by qPCR. RESULTS: PPARgamma expression was lower in subjects with
      non-CF bronchiectasis compared with healthy control subjects (control: 1.00, IQR
      0.55-1.44, n = 20 vs. Bronchiectasis: 0.49, IQR 0.12-0.89; n = 35; p<0.001, Mann
      Whitney U test). This lower PPARgamma expression correlated negatively with
      Pseudomonas aeruginosa (r = -0.53, n = 31; p = 0.002). No significant association
      was seen between PPARgamma and total bacterial levels or levels Haemophilus
      influenzae. CONCLUSION: PPARgamma is expressed in low levels in the airways of
      non-CF bronchiectasis subjects, despite an aggressive inflammatory response. This
      low level PPARgamma expression is particularly associated with the presence of
      high levels of P. aeruginosa, and may represent an intrinsic link with this
      bacterial pathogen.

PMID- 30114279
TI  - GRASShopPER-An algorithm for de novo assembly based on GPU alignments.
AB  - Next generation sequencers produce billions of short DNA sequences in a massively
      parallel manner, which causes a great computational challenge in accurately
      reconstructing a genome sequence de novo using these short sequences. Here, we
      propose the GRASShopPER assembler, which follows an approach of overlap-layout
      consensus. It uses an efficient GPU implementation for the sequence alignment
      during the graph construction stage and a greedy hyper-heuristic algorithm at the
      fork detection stage. A two-part fork detection method allows us to identify
      repeated fragments of a genome and to reconstruct them without misassemblies. The
      assemblies of data sets of bacteria Candidatus Microthrix, nematode
      Caenorhabditis elegans, and human chromosome 14 were evaluated with the golden
      standard tool QUAST. In comparison with other assemblers, GRASShopPER provided
      contigs that covered the largest part of the genomes and, at the same time, kept
      good values of other metrics, e.g., NG50 and misassembly rate.

PMID- 30114281
TI  - Antihyperuricemic and xanthine oxidase inhibitory activities of Tribulus arabicus
      and its isolated compound, ursolic acid: In vitro and in vivo investigation and
      docking simulations.
AB  - BACKGROUND: Hyperurecemia is usually associated with gout and various metabolic
      arthritis disorders. Limited medications are available to manage such conditions.
      This study aimed to isolate the triterpenes constituent of the plant and to
      assess xanthine oxidase (XO) inhibitory and antihyperuricemic activities of
      Tribulus arabicus ethanolic extract, its fractions and the isolated compound
      using in vitro and in vivo approaches. METHODS: The ethanolic extract, fractions;
      n-hexane, chloroform and n-butanol and the isolated compound (ursolic acid) were
      evaluated in vitro for their XO inhibitory activity. Those that demonstrated
      significant activity were further evaluated for their antihyperuricemic activity
      on potassium oxonate-induced hyperuricemia in mice. RESULTS: The ethanolic
      extract was found to be safe up to 5000 mg/kg. The extract and its n-hexane
      fraction exhibited significant inhibitory activity on XO, whilst only a modest
      reduction in the enzymatic activity was noticed with n-butanol and chloroform
      fractions. Furthermore, administration of the ethanolic extract at low and high
      doses significantly reduced serum urate levels in mice by 31.1 and 64.6%
      respectively. The isolated active constituent, ursolic acid, showed potent XO
      inhibition activity (Half maximal inhibitory concentration, IC50 = 10.3 MUg/mL),
      and significantly reduced uric acid level in vivo by 79.9%. Virtually, the
      binding mode of ursolic acid with XO was determined using molecular docking
      simulations. CONCLUSIONS: The activity of the ethanolic extract of T. arabicus
      and its n-hexane fraction can be attributed to the isolated compound, ursolic
      acid. Ursolic acid has good hypouricemic activity and therefore has high
      potential to be used for the treatment of gout and hyperuricemia-related
      diseases.

PMID- 30114282
TI  - Spectral effects of light-emitting diodes on plant growth, visual color quality,
      and photosynthetic photon efficacy: White versus blue plus red radiation.
AB  - Arrays of blue (B, 400-500 nm) and red (R, 600-700 nm) light-emitting diodes
      (LEDs) used for plant growth applications make visual assessment of plants
      difficult compared to a broad (white, W) spectrum. Although W LEDs are sometimes
      used in horticultural lighting fixtures, little research has been published using
      them for sole-source lighting. We grew seedlings of begonia (Begonia
      *semperflorens), geranium (Pelargonium *horturum), petunia (Petunia *hybrida),
      and snapdragon (Antirrhinum majus) at 20 degrees C under six sole-source LED
      lighting treatments with a photosynthetic photon flux density (PPFD) of 160
      MUmol?m-2?s-1 using B (peak = 447 nm), green (G, peak = 531 nm), R (peak = 660
      nm), and/or mint W (MW, peak = 558 nm) LEDs that emitted 15% B, 59% G, and 26% R
      plus 6 MUmol?m-2?s-1 of far-red radiation. The lighting treatments (with
      percentage from each LED in subscript) were MW100, MW75R25, MW45R55, MW25R75,
      B15R85, and B20G40R40. At the transplant stage, total leaf area, and fresh and
      dry weight were similar among treatments in all species. Surprisingly, when
      petunia seedlings were grown longer (beyond the transplant stage) under sole
      source lighting treatments, the primary stem elongated and had flower buds
      earlier under MW100 and MW75R25 compared to under B15R85. The color rendering
      index of MW75R25 and MW45R55 were 72, and 77, respectively, which was higher than
      those of other treatments, which were <=64. While photosynthetic photon efficacy
      of B15R85 (2.25 MUmol?J-1) was higher than the W light treatments (1.51-2.13
      MUmol?J-1), the dry weight gain per unit electric energy consumption (in g?kWh-1)
      of B15R85 was similar to those of MW25R75, MW45R55, and MW75R25 in three species.
      We conclude that compared to B+R radiation, W radiation had generally similar
      effects on seedling growth at the same PPFD with similar electric energy
      consumption, and improved the visual color quality of sole-source lighting.

PMID- 30114280
TI  - Cannabinoid 1 receptor signaling on GABAergic neurons influences astrocytes in
      the ageing brain.
AB  - Astrocytes, key regulators of brain homeostasis, interact with neighboring glial
      cells, neurons and the vasculature through complex processes involving different
      signaling pathways. It is not entirely clear how these interactions change in the
      ageing brain and which factors influence astrocyte ageing. Here, we investigate
      the role of endocannabinoid signaling, because it is an important modulator of
      neuron and astrocyte functions, as well as brain ageing. We demonstrate that mice
      with a specific deletion of CB1 receptors on GABAergic neurons (GABA-Cnr1-/-
      mice), which show a phenotype of accelerated brain ageing, affects age-related
      changes in the morphology of astrocytes in the hippocampus. Thus, GABA-Cnr1-/-
      mice showed a much more pronounced age-related and layer-specific increase in
      GFAP-positive areas in the hippocampus compared to wild-type animals. The number
      of astrocytes, in contrast, was similar between the two genotypes. Astrocytes in
      the hippocampus of old GABA-Cnr1-/- mice also showed a different morphology with
      enhanced GFAP-positive process branching and a less polarized intrahippocampal
      distribution. Furthermore, astrocytic TNFalpha levels were higher in GABA-Cnr1-/-
      mice, indicating that these morphological changes were accompanied by a more pro
      inflammatory function. These findings demonstrate that the disruption of
      endocannabinoid signaling on GABAergic neurons is accompanied by functional
      changes in astrocyte activity, which are relevant to brain ageing.

PMID- 30114283
TI  - Predicting segregation of multiple fruit-quality traits by using accumulated
      phenotypic records in citrus breeding.
AB  - In the breeding of citrus (Citrus spp.), suitable fruit quality is essential for
      consumer acceptance of new cultivars. To identify parental combinations producing
      F1 progeny with fruit-quality traits exceeding certain selection criteria, we
      developed a simple and practical method for predicting multiple-trait segregation
      in an F1 progeny population. This method uses breeding values of parental
      genotypes and an additive genetic (co)variance matrix calculated by the best
      linear unbiased prediction method to construct a model for trait segregation in
      F1 progeny. To confirm the validity of our proposed method, we calculated the
      breeding values and additive genetic (co)variances based on phenotypic records on
      nine fruit-quality traits in 2122 genotypes, and constructed a trait segregation
      model. Subsequently, we applied the trait segregation model to all pairs of the
      2122 genotypes (i.e., 2,252,503 combinations), and predicted the most promising
      combinations and evaluated their probabilities of producing superior genotypes
      exceeding the nine fruit-quality traits of satsuma mandarin (Citrus unshiu
      Marcow.) or 'Shiranuhi' ('Kiyomi' * 'Nakano No. 3' ponkan), two popular citrus
      cultivars in Japan. We consider these results to be useful not only for selecting
      good parental combinations for fruit quality or other important traits but also
      for determining the scale of breeding programs required to achieve specific
      breeding goals.

PMID- 30114284
TI  - Mottling score and skin temperature in septic shock: Relation and impact on
      prognosis in ICU.
AB  - INTRODUCTION: Mottling score, defined by 5 areas over the knee is developed to
      evaluate tissue perfusion at bedside. Because of the subjective aspect of the
      score, we aimed to compare mottling score and skin temperature in septic shock
      with infrared thermography in ICU and the correlation to survival. METHODS: We
      conducted a prospective and observational study in a teaching hospital in France
      during 8 months in ICU. All patients with sepsis requiring vasoactive drugs were
      included. We recorded epidemiologic data, hemodynamic parameters, mottling score
      and skin temperature with a thermic camera of the 5 mottling areas around the
      knee (temperatures recorded with FLIRTM software) at bedside. Measures were
      performed at ICU admission (H0) and six hours after initial resuscitation (H6).
      RESULTS: 46 patients were included. Median age was 69 (60-78), SOFA score 11 (8
      12) mean SAPS II was 57+/-20 and 28-day mortality rate was 30%. Patients with
      mottling (score>=1), had a skin temperature of the knee significantly lower (30.7
      vs 33,2 degrees C p = 0.01 at H6) than patients without mottling (score = 0).
      Skin temperatures of the knee in mottling groups 1 to 5 were similar at H0 and
      H6. Neither mottling score nor skin temperature of the knee were associated with
      prognostic regarding day-28 mortality. CONCLUSIONS: Skin temperature measured
      with infrared thermography technology around the knee is lower when mottling sign
      is present and sign microcirculation alterations. This method, compared to
      standard mottling score is objective and allows data collections. However, this
      method failed to predict mortality in ICU patients.

PMID- 30114285
TI  - The signaling peptide-encoding genes CLE16, CLE17 and CLE27 are dispensable for
      Arabidopsis shoot apical meristem activity.
AB  - The shoot apical meristem produces all of the leaves, stems and flowers of a
      flowering plant from a reservoir of stem cells at its growing tip. In
      Arabidopsis, the small polypeptide signaling molecule CLAVATA3 (CLV3), a member
      of the CLV3/EMBRYO SURROUNDING REGION-RELATED (CLE) gene family, is a key
      component of a negative feedback loop that maintains stem cell activity in shoot
      and floral meristems throughout development. Because in some plant species
      multiple CLE genes are involved in regulating shoot apical meristem activity, we
      tested the hypothesis that CLE genes other than CLV3 might function in stem cell
      homeostasis in Arabidopsis. We identified three Arabidopsis CLE genes expressed
      in the post-embryonic shoot apical meristem, generated loss-of-function alleles
      using genome editing, and analyzed the meristem phenotypes of the resulting
      mutant plants. We found that null mutations in CLE16, CLE17 or CLE27 affected
      neither vegetative nor reproductive shoot meristem activity under normal growth
      conditions, although CLE27 appears to slightly prolong vegetative growth. Our
      results indicate that the CLE16, CLE17 and CLE27 genes have largely redundant
      roles in the Arabidopsis shoot apical meristem and/or regulate meristem activity
      only under specific environmental conditions.

PMID- 30114286
TI  - Rapid-onset gender dysphoria in adolescents and young adults: A study of parental
      reports.
AB  - PURPOSE: In on-line forums, parents have been reporting that their children are
      experiencing what is described here as "rapid-onset gender dysphoria," appearing
      for the first time during puberty or even after its completion. The onset of
      gender dysphoria seemed to occur in the context of belonging to a peer group
      where one, multiple, or even all of the friends have become gender dysphoric and
      transgender-identified during the same timeframe. Parents also report that their
      children exhibited an increase in social media/internet use prior to disclosure
      of a transgender identity. The purpose of this study was to document and explore
      these observations and describe the resulting presentation of gender dysphoria,
      which is inconsistent with existing research literature. METHODS: Recruitment
      information with a link to a 90-question survey, consisting of multiple-choice,
      Likert-type and open-ended questions, was placed on three websites where parents
      had reported rapid onsets of gender dysphoria. Website moderators and potential
      participants were encouraged to share the recruitment information and link to the
      survey with any individuals or communities that they thought might include
      eligible participants to expand the reach of the project through snowball
      sampling techniques. Data were collected anonymously via SurveyMonkey.
      Quantitative findings are presented as frequencies, percentages, ranges, means
      and/or medians. Open-ended responses from two questions were targeted for
      qualitative analysis of themes. RESULTS: There were 256 parent-completed surveys
      that met study criteria. The adolescent and young adult (AYA) children described
      were predominantly female sex at birth (82.8%) with a mean age of 16.4 years.
      Forty-one percent of the AYAs had expressed a non-heterosexual sexual orientation
      before identifying as transgender. Many (62.5%) of the AYAs had been diagnosed
      with at least one mental health disorder or neurodevelopmental disability prior
      to the onset of their gender dysphoria (range of the number of pre-existing
      diagnoses 0-7). In 36.8% of the friendship groups described, the majority of the
      members became transgender-identified. The most likely outcomes were that AYA
      mental well-being and parent-child relationships became worse since AYAs "came
      out". AYAs expressed a range of behaviors that included: expressing distrust of
      non-transgender people (22.7%); stopping spending time with non-transgender
      friends (25.0%); trying to isolate themselves from their families (49.4%), and
      only trusting information about gender dysphoria from transgender sources
      (46.6%). CONCLUSION: Rapid-onset gender dysphoria (ROGD) describes a phenomenon
      where the development of gender dysphoria is observed to begin suddenly during or
      after puberty in an adolescent or young adult who would not have met criteria for
      gender dysphoria in childhood. ROGD appears to represent an entity that is
      distinct from the gender dysphoria observed in individuals who have previously
      been described as transgender. The worsening of mental well-being and parent
      child relationships and behaviors that isolate AYAs from their parents, families,
      non-transgender friends and mainstream sources of information are particularly
      concerning. More research is needed to better understand this phenomenon, its
      implications and scope.

PMID- 30114287
TI  - miRNA expression profiles of premalignant and malignant arsenic-induced skin
      lesions.
AB  - Arsenic, a naturally occurring element, contaminates the drinking water of over
      200 million people globally. Chronic arsenic exposure causes multiple cancers
      including those originating from skin, lung and bladder, and is associated with
      liver, kidney, and prostate cancers. Skin is the primary target organ for arsenic
      toxicity; chronic toxicity initially manifests as non-malignant hyperkeratoses
      (HK) and subsequently advances to malignant lesions, including squamous cell
      carcinoma (SCC) and basal cell carcinoma (BCC). In this study, we evaluate the
      miRNA expression profiles of premalignant (3 HK) and malignant (3 BCC and 3 SCC)
      skin lesions from individuals chronically exposed to high levels of arsenic (59
      172 ppb) in their drinking water in West Bengal, India. The lesions were
      histologically complex requiring histopathologic identification of keratinocytes
      to be isolated for RNA analyses. Keratinocytes were harvested using Laser Capture
      Microdissection and miRNA expression profiles were determined using TaqMan(r)
      Array Human MiRNA A Card v2.0. Thirty-five miRNAs were differentially expressed
      among the three lesion types analyzed. Two miRNAs (miR-425-5p and miR-433) were
      induced in both BCC and SCC relative to HK indicating their association with
      malignancy. Two other miRNAs (miR-184 and miR-576-3p) were induced in SCC
      relative to both BCC and HK suggesting selective induction in tumors capable of
      metastasis. Six miRNAs (miR-29c, miR-381, miR-452, miR-487b, miR-494 and miR-590
      5p) were selectively suppressed in BCC relative to both SCC and HK. In
      conclusion, the differential miRNA expression was both phenotype- and stage
      related. These miRNAs are potential biomarkers and may serve as therapy targets
      for arsenic-induced internal tumors.

PMID- 30114289
TI  - Micro-CT study of male genitalia and reproductive system of the Asian citrus
      psyllid, Diaphorina citri Kuwayama, 1908 (Insecta: Hemiptera, Liviidae).
AB  - The Asian citrus psyllid (ACP), Diaphorina citri, is a major vector of the
      bacteria Candidatus Liberibacter asiaticus and C.L. americanus, which cause
      Huanglongbing disease (HLB) (aka Citrus greening disease), considered the most
      serious bacterial disease of citrus trees. As part of a multidisciplinary project
      on psyllid biology (www.citrusgreening.org), the results presented here concern a
      detailed anatomical study of the male reproductive system (testes, seminal
      vesicles, accessory glands, sperm pump, connecting ducts, and aedeagus) using
      micro-computed tomography (micro-CT). The study summarizes current knowledge on
      psyllids male reproductive system and represents significant advances in the
      knowledge of ACP anatomy.

PMID- 30114288
TI  - Initiation of breastfeeding within one hour of birth and its determinants among
      normal vaginal deliveries at primary and secondary health facilities in
      Bangladesh: A case-observation study.
AB  - BACKGROUND: Initiation of breastfeeding within one hour of birth can avert 22% of
      newborn mortality. Several factors influence breastfeeding practice including
      mothers' socio-demographic and obstetric characteristics, and factors related to
      time around child birth. This study explores breastfeeding initiation practices
      and associated influencing factors for initiating breastfeeding within one hour
      of birth in public health facilities of Bangladesh. METHODS: In this study,
      normal deliveries were observed in 15 public health facilities from 3 districts
      in Bangladesh. Study participants were selected by convenient sampling i.e.
      delivery cases attending health facilities during the study period were selected
      excluding caesarean section deliveries. Among 249 mothers, time of initiation of
      breastfeeding was observed and its association was measured with type of health
      facility, privacy in delivery room, presence of separate staff for newborn,
      spontaneous breathing, skin-to-skin contact and postnatal contact of mother or
      newborn with health care providers within one hour after delivery. Data was
      collected during August-September, 2016. Kruskal-Wallis test was used to measure
      equality of median duration of breastfeeding initiation time among two or more
      categories of independent variables. Series of simple logistic regressions were
      conducted followed by multiple logistic regression to identify the determinants
      for breastfeeding initiation within one hour. RESULTS: Among 249 mothers
      observed, 67% initiated breastfeeding within one hour of birth at health
      facilities and median time to initiate breastfeeding was 38 minutes (Inter
      quartile range: 20-56 minutes). After controlling for maternal age as potential
      confounder, the odds of initiating breastfeeding within one hour of birth was
      significantly higher if mothers gave birth in district hospitals (AOR 3.5: 95% CI
      1.5, 6.4), visual privacy was well-maintained in delivery room (AOR 2.6: 95% CI
      1.2, 4.8), newborns cried spontaneously (AOR 4.9: 95% CI 3.4, 17.2), were put to
      skin-to-skin contact with mothers (AOR 3.4: 95% CI 1.9, 10.4) or were examined by
      health care providers in the facilities (AOR 2.4: 95% CI 1.3, 12.9). CONCLUSIONS:
      In health facilities, initiation of breastfeeding within one hour is associated
      with some critical practices and events around the time of birth. With the global
      push toward facility-based deliveries, it is very important to identify those key
      factors, within the landscape of maternal and newborn care, which significantly
      enable health care providers and parents to engage in the evidence-based newborn
      care activities including early initiation of breastfeeding that will, in turn,
      reduce global rates of newborn mortality.

PMID- 30114290
TI  - At 4.5 but not 5.5 years, children favor kin when the stakes are moderately high.
AB  - Adults report more willingness to help siblings over close friends when the
      stakes are extremely high, such as when deciding whether to donate a kidney or
      risk injury to rescue someone in peril. When dividing plentiful, low-value
      resources, in contrast, children expect people to share equally with friends and
      siblings. Even when distributing limited resources-one instead of many-and
      distributing to their own social partners rather than fictional characters,
      children share more with kin and friends than with strangers but do not favor kin
      over friends until 5.5 years of age. However, no study has tested whether
      children would preferentially benefit kin if the rewards require that children
      incur a higher personal cost of their own time and effort. In the present
      experiment, therefore, we asked if children would work harder for kin over non
      kin when playing a challenging geometry game that allowed them to earn rewards
      for others. We found that 4.5-year-old children calibrated their time and effort
      in the game differently according to who received the rewards-they played for
      more trials and answered more trials correctly for kin over non-kin, but 5.5-year
      old children did not. The older children may have found the task easier and less
      costly or may have different social experiences affecting their efforts to
      benefit others. Nonetheless, 4.5-year-old children's social decisions favored kin
      as recipients of their generosity.

PMID- 30114291
TI  - Correction: An evaluation of emergency guidelines issued by the World Health
      Organization in response to four infectious disease outbreaks.
AB  - [This corrects the article DOI: 10.1371/journal.pone.0198125.].

PMID- 30114293
TI  - Efavirenz reduces renal excretion of lamivudine in rats by inhibiting organic
      cation transporters (OCT, Oct) and multidrug and toxin extrusion proteins (MATE,
      Mate).
AB  - Efavirenz (EFV) is a non-nucleoside reverse transcriptase inhibitor used in first
      line combination antiretroviral therapy (cART). It is usually administered with
      nucleoside reverse transcriptase inhibitors (NRTI), many of which are substrates
      of OCT uptake solute carriers (SLC22A) and MATE (SLC47A), P-gp (MDR1, ABCB1),
      BCRP (ABCG2), or MRP2 (ABCC2) efflux transporters. The aim of this study was to
      evaluate the inhibitory potential of efavirenz towards these transporters and
      investigate its effects on the pharmacokinetics and tissue distribution of a
      known Oct/Mate substrate, lamivudine, in rats. Accumulation and transport assays
      showed that efavirenz inhibits the uptake of metformin by OCT1-, OCT2- and MATE1
      expressing MDCK cells and reduces transcellular transport of lamivudine across
      OCT1/OCT2- and MATE1-expressing MDCK monolayers. Only negligible inhibition of
      MATE2-K was observed in HEK-MATE2-K cells. Efavirenz also reduced the efflux of
      calcein from MDCK-MRP2 cells, but had a rather weak inhibitory effect on Hoechst
      33342 accumulation in MDCK-MDR1 and MDCK-BCRP cells. An in vivo pharmacokinetic
      interaction study in male Wistar rats revealed that intravenous injection of
      efavirenz or the control Oct/Mate inhibitor cimetidine significantly reduced the
      recovery of lamivudine in urine and greatly increased lamivudine retention in the
      renal tissue. Co-administration with efavirenz or cimetidine also increased the
      AUC0-infinity value and reduced total body clearance of lamivudine. These data
      suggest that efavirenz is a potent inhibitor of OCT/Oct and MATE/Mate
      transporters. Consequently, it can engage in drug-drug interactions that reduce
      renal excretion of co-administered substrates and enhance their retention in the
      kidneys, potentially compromising therapeutic safety.

PMID- 30114294
TI  - Understanding the dynamics of keratin weakening and hydrolysis by proteases.
AB  - Keratin is the structural protein in hair, nails, feathers and horns. Keratin is
      recalcitrant, highly disulfide bonded and is generally inaccessible to common
      proteases. Only certain types of proteases, called keratinases, are able to
      cleave the peptide bonds within the keratin structure. Due to this outstanding
      activity, keratinases have potential application in industries such as livestock,
      cosmetics and pharmaceuticals. Yet, the process of enzymatic keratin degradation
      is poorly understood, affecting the development of industrial enzyme formulations
      that may require full or only partial modification or weakening. Here we
      investigate the dynamics of keratin weakening and hydrolysis, showing that the
      decrease in hair mechanical strength is associated with cuticle removal and
      damage to the cortex and complete breakdown is dependent on reducing agents.
      Proteases with keratinolytic activity were selected and applied to hair with
      degradation examined by mechanical, biochemical and microscopic techniques. The
      extent of keratin degradation was highly enhanced by the presence of reducing
      agents, principally sodium thioglycolate, exceeding 90% degradation within 16 h
      of enzymatic treatment. Application was extended to feathers showing that the
      findings are relevant to improving the use of keratinases in a variety of
      industries. Overall, the outcomes provide valuable insights into the keratin
      degradation process by enzymes for the optimization of cosmetic and
      pharmaceutical products and for livestock waste recycling among other important
      applications.

PMID- 30114292
TI  - Orthologous proteins of experimental de- and remyelination are differentially
      regulated in the CSF proteome of multiple sclerosis subtypes.
AB  - OBJECTIVE: Here, we applied a multi-omics approach (i) to examine molecular
      pathways related to de- and remyelination in multiple sclerosis (MS) lesions; and
      (ii) to translate these findings to the CSF proteome in order to identify
      molecules that are differentially expressed among MS subtypes. METHODS: To relate
      differentially expressed genes in MS lesions to de- and remyelination, we
      compared transcriptome of MS lesions to transcriptome of cuprizone (CPZ)-induced
      de- and remyelination. Protein products of the overlapping orthologous genes were
      measured within the CSF by quantitative proteomics, parallel reaction monitoring
      (PRM). Differentially regulated proteins were correlated with molecular markers
      of inflammation by using MesoScale multiplex immunoassay. Expression kinetics of
      differentially regulated orthologous genes and proteins were examined in the CPZ
      model. RESULTS: In the demyelinated and remyelinated corpus callosum, we detected
      1239 differentially expressed genes; 91 orthologues were also differentially
      expressed in MS lesions. Pathway analysis of these orthologues suggested that the
      TYROBP (DAP12)-TREM2 pathway, TNF-receptor 1, CYBA and the proteasome subunit
      PSMB9 were related to de- and remyelination. We designed 129 peptides
      representing 51 orthologous proteins, measured them by PRM in 97 individual CSF,
      and compared their levels between relapsing (n = 40) and progressive MS (n = 57).
      Four proteins were differentially regulated among relapsing and progressive MS:
      tyrosine protein kinase receptor UFO (UFO), TIMP-1, apolipoprotein C-II (APOC2),
      and beta-2-microglobulin (B2M). The orthologous genes/proteins in the mouse brain
      peaked during acute remyelination. UFO, TIMP-1 and B2M levels correlated
      inversely with inflammation in the CSF (IL-6, MCP-1/CCL2, TARC/CCL17). APOC2
      showed positive correlation with IL-2, IL-16 and eotaxin-3/CCL26. CONCLUSIONS:
      Pathology-based multi-omics identified four CSF markers that were differentially
      expressed in MS subtypes. Upregulated TIMP-1, UFO and B2M orthologues in
      relapsing MS were associated with reduced inflammation and reflected reparatory
      processes, in contrast to the upregulated orthologue APOC2 in progressive MS that
      reflected changes in lipid metabolism associated with increased inflammation.

PMID- 30114295
TI  - Exploring the needs and possibilities of physicians' continuing professional
      development - An explorative qualitative study in a Chinese primary care context.
AB  - BACKGROUND: One component of the 2009 Chinese health care reform plan is to train
      general practitioners to improve the delivery of primary care services. This
      continuing professional development is expected to further improve the
      physicians' competencies to be general practitioners in primary care. Augmented
      reality-a combination of virtual information and the real environment-may enhance
      general practitioners' continuing professional development by allowing their
      learning experiences to overlap with their workplace practice. OBJECTIVE: To
      explore the needs, opportunities, and challenges involved in continuing
      professional development for Chinese physicians becoming competent general
      practitioners within primary care, with a special focus on the possibilities of
      applying augmented reality. METHODS: This study used a qualitative approach with
      semi-structured face-to-face interviews. Two managers and thirteen physicians
      (from four community health centers and stations) participated. The data were
      analyzed using a thematic inductive analysis approach. RESULTS: Based on our
      interviews, most of the physicians were not fully trained as general
      practitioners but still assumed the duties of that position; they were supposed
      to eventually become fully trained in line with the reforms of the Chinese
      primary care system. However, they reported a lack of in-service training
      opportunities to fulfill this goal. Even those who said that they had such
      opportunities perceived the efficacy of that training as being poor. The managers
      and most of the physicians reacted positively to the idea of using augmented
      reality in continuing professional development, and they suggested antibiotics
      treatment, surgery, and emergency care as learning areas in which augmented
      reality could be applied. CONCLUSIONS: Due to the Chinese reforms of the primary
      care system, both managers and the physicians themselves expect general
      practitioners to become qualified by engaging in continuing professional
      development. Both groups also regarded augmented reality as a potentially useful
      tool.

PMID- 30114297
TI  - In Memoriam: Prof Smail Zubcevic, MD, PhD (1958-2017).

PMID- 30114298
TI  - Letter to the Editor: Optical Coherence Tomography Angiography of Choroidal
      Hemangioma.

PMID- 30114299
TI  - Practical Pearls in Pediatric Vitreoretinal Surgery.

PMID- 30114300
TI  - Predictors of Visual Acuity Outcomes Following Vitrectomy for Idiopathic Macular
      Hole.
AB  - BACKGROUND AND OBJECTIVE: To investigate predictors of visual outcomes in
      patients who underwent vitrectomy for full-thickness macular hole (FTMH) with at
      least 1 year of follow-up. PATIENTS AND METHODS: Retrospective, noncomparative,
      consecutive case series of 132 eyes of 122 patients who underwent surgical repair
      of idiopathic FTMH with at least 1 year of follow-up. Predictors of visual acuity
      (VA) outcomes were analyzed using linear regression. RESULTS: Mean follow-up time
      was 22.2 months. Twenty-three eyes (17.4%) had age-related macular degeneration
      (AMD), of which 17 (73.9%) cases were mild and nonexudative. At final follow-up,
      poor preoperative VA (P < .001), perioperative complications (P < .001), AMD (P <
      .001), and delay from preoperative evaluation to surgery (P = .037) were
      significant predictors of final VA. In multiple regression, these variables
      remained significant (P < .001, P = .011, P < .001, and P = .002, respectively).
      CONCLUSION: Poor preoperative VA, perioperative complications, AMD, and delay to
      surgery were significant predictors of final VA following FTMH repair.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:566-570.].

PMID- 30114296
TI  - Pre-clinical evaluation of quinoxaline-derived chalcones in tuberculosis.
AB  - New effective compounds for tuberculosis treatment are needed. This study
      evaluated the effects of a series of quinoxaline-derived chalcones against
      laboratorial strains and clinical isolates of M. tuberculosis. Six molecules,
      namely N5, N9, N10, N15, N16, and N23 inhibited the growth of the M. tuberculosis
      H37Rv laboratorial strain. The three compounds (N9, N15 and N23) with the lowest
      MIC values were further tested against clinical isolates and laboratory strains
      with mutations in katG or inhA genes. From these data, N9 was selected as the
      lead compound for further investigation. Importantly, this chalcone displayed a
      synergistic effect when combined with moxifloxacin. Noteworthy, the anti
      tubercular effects of N9 did not rely on inhibition of mycolic acids synthesis,
      circumventing important mechanisms of resistance. Interactions with cytochrome
      P450 isoforms and toxic effects were assessed in silico and in vitro. The
      chalcone N9 was not predicted to elicit any mutagenic, genotoxic, irritant, or
      reproductive effects, according to in silico analysis. Additionally, N9 did not
      cause mutagenicity or genotoxicity, as revealed by Salmonella/microsome and
      alkaline comet assays, respectively. Moreover, N9 did not inhibit the cytochrome
      P450 isoforms CYP3A4/5, CYP2C9, and CYP2C19. N9 can be considered a potential
      lead molecule for development of a new anti-tubercular therapeutic agent.

PMID- 30114302
TI  - Normative Data on Foveal Avascular Zone Dimensions in Four Macular Vascular
      Layers.
AB  - BACKGROUND AND OBJECTIVES: To provide normative data on the size of the foveal
      avascular zone (FAZ) in the four histological retinal vascular layers as measured
      using optical coherence tomography angiography (OCTA) and evaluate interobserver
      variability. PATIENTS AND METHODS: Two graders measured the FAZ area in each
      layer (nerve fiber layer [NFL], ganglion cell layer [GCL], inner plexiform layer
      to inner nuclear layer [INL], and INL to outer plexiform layer), as well as the
      superficial and deep capillary plexuses. RESULTS: Forty-seven eyes of 25 subjects
      were included. The FAZ was not clearly delineated in the NFL or GCL layers. There
      was high agreement between measurements of the FAZ area of the different layers.
      Inter- and intraobserver agreements were high. CONCLUSION: This is the first
      study to measure FAZ size across the retina. There was a high correlation between
      FAZ sizes among the different layers on OCTA. [Ophthalmic Surg Lasers Imaging
      Retina. 2018;49:580-586.].

PMID- 30114301
TI  - First-Operated and Fellow Eyes With Bilateral Idiopathic Macular Hole: Comparison
      of Anatomical and Functional Postoperative Outcomes.
AB  - BACKGROUND AND OBJECTIVE: To report anatomical and functional outcomes of surgery
      in each of the eyes in cases of bilateral macular hole (MH). PATIENTS AND
      METHODS: The anatomical and functional results for 42 patients with bilateral
      idiopathic MH were evaluated retrospectively. First-operated and fellow eyes were
      compared at various time points for preoperative characteristics and
      postoperative outcomes. RESULTS: Anatomical success was achieved in all patients
      after a single operation, and no reopening of an initially closed MH was observed
      during the follow-up period. There was a statistically significant difference
      between the first and fellow eyes in mean postoperative logMAR visual acuity (VA)
      (P = .048). Fellow eyes had better postoperative VA, lower rates of ellipsoid
      zone, and interdigitation zone disruption, and none of the fellow eyes had
      external limiting membrane disruption at any time after surgery. CONCLUSIONS:
      Although anatomical success can be achieved in both eyes after successful
      surgery, early detection and treatment of fellow eyes is associated with better
      postoperative VA. The reason for a better outcome in the fellow eye is related to
      the lower photoreceptor impairment rate because of the earlier stage of the hole.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:571-578.].

PMID- 30114303
TI  - Prediction of Visual Acuity After Cataract Surgery Using Optical Coherence
      Tomography Findings in Eyes With Retinitis Pigmentosa.
AB  - BACKGROUND AND OBJECTIVE: To investigate the predictive factors of visual acuity
      (VA) after cataract surgery in patients with retinitis pigmentosa (RP). PATIENTS
      AND METHODS: Retrospective, observational study. The authors reviewed a
      consecutive series of 70 patients (109 eyes) with RP who underwent cataract
      surgery. The changes in best-corrected visual acuity (BCVA) before and 3 months
      after surgery were measured. The relationship between preoperative ellipsoid zone
      (EZ) conditions, external limiting membrane (ELM) conditions, central macular
      thickness (CMT), and postoperative BCVA were investigated. RESULTS: The mean BCVA
      was significantly improved after cataract surgery from 0.80 to 0.45 (P < .001).
      However, final BCVA did not improve in 57 eyes (52.3%). The mean postoperative
      BCVA was significantly better in eyes with an intact ELM than those without (P <
      .001), in eyes with an intact EZ than those without (P < .001), and in eyes with
      relatively normal CMT (>= 200 MUm) than those with decreased CMT (< 200 MUm) (P <
      .001). In multiple linear regression analysis, preoperative logMAR VA (P < .001),
      ELM integrity (P < .001), and CMT (P = .017) remained the only three variables
      that were associated significiantly with postoperative BCVA (R2 = 0.753; P <
      .001). CONCLUSIONS: Postoperative BCVA in approximately half of the eyes was
      improved after cataract surgery in patients with RP. The preoperative BCVA and
      the status of ELM and CMT are important parameters to predict postoperative VA.
      [Ophthalmic Surg Lasers Imaging Retina. 2018;49:587-594.].

PMID- 30114304
TI  - Relationship Between Metamorphopsia and Macular Parameters Before and After
      Idiopathic Macular Hole Surgery.
AB  - BACKGROUND AND OBJECTIVE: To investigate changes in the pattern of metamorphopsia
      in patients after idiopathic macular hole (MH) surgery and the relationship
      between metamorphopsia, visual acuity (VA), and macular parameters. PATIENTS AND
      METHODS: This prospective, interventional study included 53 eyes of 53 patients
      with idiopathic full-thickness MH. The severity of metamorphopsia was quantified
      using M-CHARTs. Minimal and basal diameter of MH and disrupted length of
      ellipsoid zone were measured using spectral-domain optical coherence tomography.
      RESULTS: Preoperative mean M-score was significantly improved from 0.95 (0.73
      1.60) (expressed as median [25% percentile, 75% percentile]) to 0.5 (0.28-0.63)
      after surgery (Z = -5.573; P < .001). Postoperative mean M-score was
      significantly correlated with mean minimal diameter of MH, preoperative mean M
      score, and preoperative logMAR best-corrected VA. Multiple regression analysis
      verified that postoperative mean M-score was significantly correlated with mean
      minimal diameter of MH (adjusted r2 = 0.113; P = .008). CONCLUSION:
      Metamorphopsia and VA were significantly improved after successful MH surgery.
      Mean minimal diameter of MH is valuable prognostic factor to metamorphopsia after
      MH surgery. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:595-602.].

PMID- 30114305
TI  - Choriocapillaris Hypoperfusion Artifact in OCT Angiography.
AB  - BACKGROUND AND OBJECTIVE: To illustrate how optical coherence tomography (OCT)
      angiography (OCTA) can be misinterpreted if not evaluated along with structural
      en face OCT to analyze the signal intensity. PATIENTS AND METHODS: Patients with
      different macular diseases associated with suspicious flow impairment in the
      choriocapillaris were recruited to be imaged on the RTVue XR Avanti device
      (Optovue, Fremont, CA) with the Angio Retina mode. En face OCT angiograms,
      structural en face OCT, and corresponding OCT B-scans with flow signal overlaid
      were compared to evaluate the correspondence of signal strength to areas of flow
      reduction in the choriocapillaris. RESULTS: Six eyes from six patients were
      enrolled. Macular lesions evaluated in this study included acute central serous
      chorioretinopathy, paracentral acute middle maculopathy, age-related macular
      degeneration, adult-onset foveomacular vitelliform dystrophy, and branch retinal
      vein occlusion. In all cases, areas of suspicious flow decrement in the
      choriocapillaris corresponded to hyporeflective areas in the intensity en face
      OCT. Thus, a precise confirmation of choriocapillaris flow impairment was not
      possible. CONCLUSION: It is essential to be aware of the importance of analyzing
      the structural image alongside with the flow image to interpret flow impairment.
      This is more important in subretinal pigment epithelial structures such as
      choriocapillaris and choroid. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:603
      610.].

PMID- 30114306
TI  - Repeat Surgery in Failed Primary Vitrectomy for Macular Holes Operated With the
      Inverted ILM Flap Technique.
AB  - BACKGROUND AND OBJECTIVE: Effects of repeat surgery in failed primary full
      thickness macular hole (FTMH) closure with the inverted internal limiting
      membrane (ILM) flap technique. PATIENTS AND METHODS: Retrospective analysis of
      patients operated with the inverted ILM flap technique. Optical coherence
      tomography was performed before initial and secondary surgeries and then at up to
      12 months post-surgery. RESULTS: During the second surgery, the inverted ILM flap
      created at the first attempt had returned to its original position, instead of
      covering the FTMH. FTMH was closed in 29 eyes after second surgery (89%) and in
      all eyes after third surgery. Visual acuity improved in 28 of 32 cases (87.5%).
      The tamponade used (either silicone oil or air) did not influence final visual
      results (P = .06). CONCLUSIONS: Repeat surgery with the inverted ILM flap
      technique is an effective method of treatment. Silicone oil improved anatomical
      outcome after second surgery but did not influence visual results. [Ophthalmic
      Surg Lasers Imaging Retina. 2018;49:611-618.].

PMID- 30114307
TI  - Localization of Paracentral Acute Middle Maculopathy Using Optical Coherence
      Tomography Angiography.
AB  - Paracentral acute middle maculopathy (PAMM) refers to band-like hyperreflective
      lesions seen on spectral-domain optical coherence tomography, mostly confined to
      the inner nuclear layer. It has been previously demonstrated to involve the deep
      capillary plexus (DCP) using optical coherence tomography angiography (OCTA). A
      29-year-old female presented with PAMM and was investigated using a new OCTA
      system that shows not just the superficial capillary plexus and DCP, but also the
      four vascular plexuses as previously demonstrated in histology. Using this
      system, involvement of the DCP was shown, but also of more superficial layers,
      including the intermediate capillary plexus. [Ophthalmic Surg Lasers Imaging
      Retina. 2018;49:619-624.].

PMID- 30114308
TI  - Late ROP Reactivation and Retinal Detachment in a Teenager.
AB  - Exudative and tractional retinal detachments have been reported as late sequelae
      of retinopathy of prematurity (ROP). The authors report a case of unilateral
      retinal detachment in a 19-year-old patient with history of peripheral ablation
      for ROP in the contralateral eye. This late reactivation is likely due to
      persistent avascular retina producing constant low levels of vascular endothelial
      growth factor. Therefore, close follow-up and ablation of peripheral avascular
      retina should be considered in patients with ROP, regardless of treatment
      history, to decrease lifelong risk of severe complications, including retinal
      detachment decades later. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:625
      628.].

PMID- 30114309
TI  - Aggressive Posterior Retinopathy of Prematurity and a TUBA1A Mutation inde
      Morsier Syndrome.
AB  - The authors report a case of a premature male neonate born at 25.3 weeks
      gestational age weighing 605 grams with septo-optic dysplasia (SOD) and a
      heterozygous mutation in TUBA1A c.715A>C, a critical gene for microtubules, who
      developed asymmetric and aggressive posterior retinopathy of prematurity (ROP).
      This report presents a novel mutation associated with SOD and proposes that optic
      nerve hypoplasia may have potentiated a severe ROP phenotype. [Ophthalmic Surg
      Lasers Imaging Retina. 2018;49:629-632.].

PMID- 30114310
TI  - Acute Macular Neuroretinopathy Phenotype in Behcet's Disease.
AB  - Acute macular neuroretinopathy (AMN) is a rare disease, the etiology of which
      remains unclear. An ischemic event at the level of the deep capillary plexus has
      been proposed. The authors present three cases of AMN in the context of active
      systemic Behcet's disease, with the support of multimodal imaging. All patients
      were known to have Behcet's disease before the diagnosis of AMN. AMN was
      confirmed in all three cases on spectral domain optical coherence tomography (SD
      OCT), near infrared reflectance and OCT angiography. Behcet's disease is known to
      be a prothrombotic disease. The presentation of AMN in this context supports the
      presumed ischemic etiology of AMN. [Ophthalmic Surg Lasers Imaging Retina.
      2018;49:634-638.].

PMID- 30114311
TI  - Optical Coherence Tomography Angiography for Evaluation of Sattler's Layer in
      Vogt-Koyanagi-Harada Disease.
AB  - The authors report a case of acute Vogt-Koyanagi-Harada syndrome with massively
      impaired perfusion in the Sattler's layer on optical coherence tomography
      angiography (OCTA). The hypoperfusion fully resolved during a period of 4 weeks
      and correlated well with hypofluorescent spots on indocyanine green angiography.
      This is the first time reduced perfusion in Sattler's layer has been observed on
      OCTA. This finding may aid further understanding of the pathology underlying VKH
      syndrome and indicates that evaluation of deeper choroidal layers like Sattler's
      layer may be of importance for disease monitoring and predicting prognosis in
      choroidal diseases. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:639-642.].

PMID- 30114312
TI  - Active Iris in Retinopathy of Prematurity and Regression Following Intravitreal
      Ranibizumab Injection.
AB  - Classic active iris vasculature in retinopathy of prematurity is shown, as well
      as regression within 24 hours of off-label ranibizumab injection (0.25 mg) in
      both eyes. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:643-644.].

PMID- 30114313
TI  - Biopsy of a Choroidal Melanoma Using Transvitreal Pars Plana Vitrectomy.
AB  - Determining when a previously benign choroidal nevi becomes malignant can be
      challenging, as traditional biopsy methods are often invasive and can lead to
      secondary complications such as endophthalmitis and vitreous hemorrhage. Using a
      transvitreal approach with the 27-gauge vitrectomy system provides several
      advantages, including direct visualization, theoretically lower risk of
      inadvertent seeding, and collection of a larger sample size. In this video, the
      authors present their technique for transvitreal biopsy of choroidal lesions
      using the 27-gauge vitreous cutter.

PMID- 30114314
TI  - Tree of death: The role of fossils in resolving the overall pattern of plant
      phylogeny.

PMID- 30114315
TI  - Prospective implementation of a standardized screening protocol for deep venous
      thrombosis in abdominal surgical oncology patients.
AB  - BACKGROUND AND OBJECTIVES: Venous thromboembolism (VTE) remains a major cause of
      perioperative morbidity and mortality despite implementation of prophylaxis
      guidelines. We sought to identify risk factors for occult deep venous thrombosis
      (DVT) following abdominal surgery for cancer and measure the clinical impact of a
      prospectively implemented standardized postoperative DVT screening protocol.
      METHODS: Patients undergoing abdominal surgery for malignant indication were
      screened with early postoperative lower extremity duplex to identify DVT.
      Clinical and pathologic factors associated with DVT were identified. RESULTS:
      Among 255 patients meeting study criteria, 25 (9.8%) had occult lower extremity
      DVT on routine postoperative screening. Prior history of VTE and lower
      preoperative hemoglobin were independently associated with DVT (OR, 9.05; P =
      0.004; and OR, 1.27; P = 0.025, respectively). Preoperative chemotherapy within 1
      year and thrombocytopenia were associated with DVT in univariate analyses only.
      Five patients developed postoperative pulmonary emboli (2.0%); three following
      negative duplex and two following positive duplex for distal DVT for which the
      patients were not therapeutically anticoagulated due to a contraindication. There
      were no pulmonary emboli in duplex-positive patients who were anticoagulated or
      who had vena cava filter placed. CONCLUSION: Despite prophylaxis, the prevalence
      of occult DVT in abdominal oncologic surgery patients is considerable.
      Postoperative screening duplex can identify these events to guide management.

PMID- 30114316
TI  - MR lymphography in patients with upper limb lymphedema: The GPS for feasibility
      and surgical planning for lympho-venous bypass.
AB  - BACKGROUND AND OBJECTIVES: Lymphedema is caused by insufficient lymphatic
      drainage leading to abnormal accumulation of interstitial fluid within soft
      tissues. Lympho-venous anastomosis (LVA), as a surgical option for selected
      patients, is widely applied. Through preoperative localization of functional
      lymphatics with indocyanine green, real time visualization of functioning
      lymphatic vessels is possible. This examination is time consuming and operator
      dependant and is not suitable to differentiate the ratio of fat hypertrophy to
      liquid edema. We investigated whether MR lymphangiography is accurate for imaging
      functional lymphatics and adjacent veins in arms. Furthermore, we investigated
      the accuracy and predictability of preoperative mapping for the feasibility of
      performing LVA and the preoperative decision making in lymphedema surgery.
      METHODS: A prospective study was performed in which 25 patients suffering from
      lymphedema of the upper extremity were examined. MR lymphography with contrast
      agent injection in a deep dermal plane was performed. RESULTS: Precise
      localization of lymphatic vessels crossing a vein was achieved in 18 of 25 arms.
      In 16 of the 18 patients in whom functional lymphatics were localized with an
      adjacent vein on MRI an LVA was performed successfully. CONCLUSIONS: MR
      lymphangiography is an accurate and reproducible method for imaging and mapping
      of lymphatic channels in the lymphedemateous limb.

PMID- 30114317
TI  - Canopy structure affects temperature distributions and free convection in moss
      shoot systems.
AB  - PREMISE OF THE STUDY: Nonvascular plants play important roles in exchange of
      water and heat at the soil-atmosphere interface. Differential evaporative cooling
      may cause temperature gradients within bryophyte canopies, influencing convective
      heat and mass transport. Understanding mechanisms that affect fluxes through moss
      layers should improve models of forest floor function. METHODS: A three
      dimensional thermal imaging system measured temperature distributions within moss
      shoot systems that were used to explore relationships among canopy structure,
      temperature gradients, evaporation, and conductance to water vapor (gs ). We
      studied five moss species under dark and light conditions in the lab. Also, these
      properties were measured in two species that differed in canopy structure during
      drying. KEY RESULTS: Differential evaporative cooling led to a 1.4 to 5.0 degrees
      C range in shoot temperatures within canopies. Samples displayed -0.5 to -0.9
      degrees C/cm temperature gradients with cooler apical temperatures. Gradient
      magnitudes did not differ among species, but taller canopies expressed greater
      temperature differences. Light enhanced both the gradient and the temperature
      difference. Rates of evaporation were significantly related to canopy height in
      the light, but not in the dark, although gs was positively associated with canopy
      height in both. Rayleigh (Ra) numbers characterize whether temperature gradients
      likely generate free convection. In tall canopies, Ra numbers exceeded the value
      indicative of free convection and turbulent flow. As plants dried, temperature
      gradients decreased. CONCLUSIONS: When moss canopies are wet, cooler apical
      temperatures create thermal instabilities within the canopies that appear
      sufficient to enhance convective transport of water vapor and heat in tall
      canopies with low bulk density.

PMID- 30114318
TI  - Selection of small plasma peptides for the auxiliary diagnosis and prognosis of
      epithelial ovarian cancer by using UPLC/MS-based non-targeted and targeted
      analyses.
AB  - Epithelial ovarian cancer (EOC) is the leading cause of gynecologic cancer
      related death due to its non-specific characteristics compared to benign cases
      and poor prognosis after conventional therapies. Small peptides (SPs)
      demonstrated to have potential for diagnosis and prognosis were focused on in
      this study for the discovery of biomarkers that address these issues. Metabolic
      profiles of fifteen SPs, including nine dipeptides and six tripeptides were
      acquired from plasma samples of 140 EOC and 158 benign ovarian tumor (BOT)
      patients. Partial least square discriminant analysis showed separations between
      EOC and BOT subjects of different age brackets. Hyp-Leu, Glu-Trp and Phe-Phe were
      selected as promising predictive SP-biomarkers for better EOC diagnosis compared
      to conventional biomarkers. Combined Hyp-Leu, Glu-Trp and CA125 presented an area
      under the curve (AUC) of 0.904, with a sensitivity and specificity of 0.804 and
      0.944, respectively. This finding suggested that the combination of these
      biomarkers performed much better than CA125 alone. Hyp-Leu and Gly-Phe-Trp showed
      significantly improved performances in the log-rank tests and Kaplan-Meier curves
      demonstrating their prognostic potential. All SP-biomarkers proved to have
      excellent stabilities at room temperature. Correlation network analysis implied
      latent conversions among amino acids, dipeptides and tripeptides during EOC. In
      conclusion, the selected SPs in combination with CA125 show profound promise for
      discriminating EOCs from BOTs and for predicting the progression after surgery,
      which provides invaluable information for clinicians in the precision diagnosis
      and treatment of EOC. This article is protected by copyright. All rights
      reserved.

PMID- 30114320
TI  - Recent Advances of MOFs and MOF-Derived Materials in Thermally Driven Organic
      Transformations.
AB  - Owing to the almost boundless structural tunability, MOF and MOF-derived
      catalysts have recently exhibited structures of higher complexity, and hence,
      have demonstrated activity in a wide array of organic transformations. These
      reactions have a broad range of important applications ranging from
      pharmaceuticals to agriculture. Given the increasing number of publications in
      the area, this Minireview is focused on the most recent advancements in thermally
      driven organic transformations using both MOFs, nanoparticle@MOF (NP@MOF)
      composites, and several classes of MOF-derived materials. The most recent
      advancements made in materials design and the utility of these materials in a
      broad range of reactions are discussed.

PMID- 30114319
TI  - Measurement of circulating transcript levels (NETest) to detect disease
      recurrence and improve follow-up after curative surgical resection of well
      differentiated pancreatic neuroendocrine tumors.
AB  - BACKGROUND: Recurrence of pancreatic neuroendocrine tumors (pNET) after surgery
      is common. Strategies to detect recurrence have limitations. We investigated the
      role of clinical criteria and the multigene polymerase chain reaction-based
      NETest during post-operative follow-up of pNET. METHODS: We studied 3 groups of
      resections: R0 with no recurrence (n = 11), R0 with recurrence (n = 12), and R1
      with no recurrence (n = 12). NETest levels (>40%) were compared with chromogranin
      A (CgA) and clinicopathological criteria (CC; grade, lymph node metastases,
      size). Nonparametric, receiver operating characteristics, logistic regression,
      and predictive feature importance analyses were performed. RESULTS: NETest was
      higher in R0 with recurrence (56 +/- 8%) compared with R1 with no recurrence (39
      +/- 6%) and R0 with no recurrence (28 +/- 6%, P < .005). NETest positively
      correlated with recurrence (area under the curve: 0.82), CgA was not (area under
      the curve: 0.51 +/- 0.09). Multiple regression analysis defined factor impact as
      highest for NETest (P < .005) versus CC (P < .03) and CgA (P = .23). NETest gave
      false positive or negative recurrence in 18% using a 40% cutoff. Logistic
      regression modeling of CC was 83% accurate; it was 91% when the NETest was
      included. Combining CC and NETest was approximately 2* more effective than
      individual CC alone (increase in R 2 value from 43% to 80%). CONCLUSIONS: A
      multigene blood test facilitates effective identification of pNET recurrence,
      prediction of disease relapse, and outperforms CgA.

PMID- 30114321
TI  - Oncologic outcomes after robot-assisted versus laparoscopic distal
      pancreatectomy: Analysis of the National Cancer Database.
AB  - BACKGROUND: How the oncologic outcomes after robotic distal pancreatectomy (RDP)
      compare to those after laparoscopic distal pancreatectomy (LDP) remains unknown.
      METHODS: Using the National Cancer Database (NCDB), we analyzed all patients
      undergoing LDP or RDP for resectable pancreatic adenocarcinoma over a 4-year
      period (2010-2013). RESULTS: Of the 704 eligible patients, 605 (86%) underwent
      LDP and 99 (14%) underwent RDP. The median follow-up for patients was 25 months.
      There were no differences in the two groups with respect to sociodemographic,
      clinicopathologic, or treatment characteristics. On comparing LDP versus RDP,
      there was no difference in the margin-positive rate (15% vs 16%; P = 0.84); lymph
      nodes examined (12 vs 11; P = 0.67); overall survival (hazard ratio [HR], 1.1,
      95% confidence intervals [CI], 0.7 to 1.7; 28 vs 25 months; P = 0.71); hospital
      stay (6 vs 5 days; P = 0.14); time to chemotherapy (50 vs 52 days; P = 0.65); 30
      day readmission (9.4% vs 9.1%; P = 0.92); and mortality (1% vs 0%; P = 0.28).
      Patients undergoing LDP had a significantly higher conversion rate to open or
      minimally invasive pancreatic cancer resections compared with RDP (27% vs 10%; P
      < 0.001). CONCLUSION: The early national experience with RDP demonstrates similar
      oncologic outcomes to LDP, with a significantly lower conversion rate.

PMID- 30114322
TI  - The use of variable temperature 13 C solid-state MAS NMR and GIPAW DFT
      calculations to explore the dynamics of diethylcarbamazine citrate.
AB  - Experimental 13 C solid-state magic-angle spinning (MAS) Nuclear Magnetic
      Resonance (NMR) as well as Density-Functional Theory (DFT) gauge-including
      projector augmented wave (GIPAW) calculations were used to probe disorder and
      local mobility in diethylcarbamazine citrate, (DEC)+ (citrate)- . This compound
      has been used as the first option drug for the treatment of filariasis, a disease
      endemic in tropical countries and caused by adult worms of Wuchereria bancrofti,
      which is transmitted by mosquitoes. We firstly present 2D 13 C?1 H dipolar
      coupling-mediated heteronuclear correlation spectra recorded at moderate spinning
      frequency, to explore the intermolecular interaction between DEC and citrate
      molecules. Secondly, we investigate the dynamic behavior of (DEC)+ (citrate)- by
      varying the temperature and correlating the experimental MAS NMR results with DFT
      GIPAW calculations that consider two (DEC)+ conformers (in a 70:30 ratio) for
      crystal structures determined at 293 and 235 K. Solid-state NMR provides insights
      on slow exchange dynamics revealing conformational changes involving particularly
      the DEC ethyl groups.

PMID- 30114324
TI  - On the importance of accurate nuclear quadrupole moments in NMR crystallography.

PMID- 30114323
TI  - Quality of life and sexual well-being after nipple sparing mastectomy: A matched
      comparison of patients using the breast Q.
AB  - BACKGROUND: Nipple sparing mastectomy (NSM) is considered safe for select
      patients. Our objective was to examine quality of life (QOL) and satisfaction for
      NSM compared with skin sparing mastectomy (SSM). We aimed to evaluate these using
      the BREAST-Q. METHODS: After IRB approval, we analyzed patients who underwent NSM
      and reconstruction between July 2010-June 2015. NSM patients were matched with
      those after SSM based on age, race, and body mass index. Telephone interviews
      were prospectively conducted using the BREAST-Q Mastectomy Postoperative Module.
      Bivariate analysis and a paired samples t-test were performed. RESULTS: We
      identified 43 patients meeting our inclusion criteria with a response rate 60% (N
      = 26). NSM and SSM patients were matched well in age (P = 1.00), race (P = 1.00),
      and Body Mass Index (P = 0.99). There were no significant differences in stage,
      estrogen and progesterone status, HER2 expression, reconstruction type and
      radiation. Mean BREAST-Q scores did not vary between NSM and SSM in regards to
      satisfaction with breasts (P = 0.604), psychosocial well-being (P = 0.146),
      physical well-being (P = 0.121), and satisfaction with surgeon (P = 0.170).
      Sexual well-being was significantly higher in NSM patients (P = 0.011).
      CONCLUSION: NSM provides patients with favorable results in psychosocial, sexual,
      and physical well-being and overall satisfaction. Sexual well-being showed
      significant improvement for NSM.

PMID- 30114325
TI  - Regulation of vasoactive intestinal peptide receptor (VPAC) signaling in
      Undifferentiated hen granulosa cells.

PMID- 30114326
TI  - Palladium-Catalyzed Reductive [5+1] Cycloaddition of 3-Acetoxy-1,4-enynes with
      CO: Access to Phenols Enabled by Hydrosilanes.
AB  - A new palladium-catalyzed reductive [5+1] cycloaddition of 3-acetoxy-1,4-enynes
      with CO, enabled by hydrosilanes, has been developed for delivering valuable
      functionalized phenols. This methodology employs hydrosilanes as the external
      reagent to facilitate the [5+1] carbonylative benzannulation. The reaction is a
      conceptually and mechanistically novel carbonylative cycloaddition route for the
      construction of substituted phenols, through the formation of four new chemical
      bonds, with excellent functional-group tolerance.

PMID- 30114327
TI  - Determination of tocopherols and tocotrienols in human breast adipose tissue with
      the use of high performance liquid chromatography-fluorescence detection.
AB  - Tocopherols and tocotrienols have been extensively studied owing to their
      anticancer potential, especially against breast cancer. Therefore, the aim of
      this study was to quantitatively determine tocochromanols in human breast adipose
      tissue with the use of HPLC-FLD. The sample preparation procedure included
      homogenization and solvent extraction with isopropanol-ethanol-0.1% formic acid
      mixture prior to solid-phase extraction. After implementation of central
      composite design, satisfactory separation of all eight target compounds was
      achieved within 10.5 min. Chromatographic runs were carried out with the use of a
      naphthylethyl chromatographic column with methanol-water mixture (89:11, v/v) as
      the mobile phase. Fluorescence detection of tocochromanols was performed with
      excitation and emission wavelengths 298 and 330 nm, respectively. The method was
      validated in terms of linearity, carryover, recovery, precision, accuracy and
      stability. Extraction yield was also determined for accurate evaluation of
      vitamin E content in human breast adipose tissue samples. Finally, concentrations
      of particular tocochromanols compounds were assessed in human breast adipose
      tissue samples obtained from 99 patients, including women with breast cancer,
      healthy volunteers and deceased women who had died as a result of accidents. The
      raw data was transformed according to the newly developed equation for accurate
      estimation of the concentrations of tocochromanols in breast adipose tissue
      samples. Results obtained in the study indicated that the proposed analytical
      assay could be useful in breast cancer research.

PMID- 30114328
TI  - Survival benefits with the addition of adjuvant hysterectomy to radiochemotherapy
      for treatment of stage I-II adenocarcinoma of the uterine cervix.
AB  - BACKGROUND AND OBJECTIVES: To determine the survival benefits of additional
      adjuvant hysterectomy in the International Federation of Gynecology and
      Obstetrics (FIGO) stage I-II cervical adenocarcinoma patients treated with
      radiochemotherapy. METHODS: Patients with FIGO stage I-II cervical adenocarcinoma
      were selected from the Surveillance, Epidemiology, and End Results 18 Regs
      research database. Propensity score matching (PSM) was used to balance patient
      baseline characteristics. Patient characteristics and outcomes were compared
      between the two groups. RESULTS: A total of 530 patients were included, 389
      (73.4%) underwent definitive radiochemotherapy and 141 (26.6%) underwent an
      additional adjuvant hysterectomy. The multivariate Cox analysis surgery was shown
      to be an independent predictor of survival. Before PSM, the hazard ratios for
      cause-specific survival and overall survival in the surgery group were 0.632 (P =
      0.036) and 0.674 (P = 0.041), respectively. After PSM, the respective hazard
      ratios were 0.392 (P < 0.001) and 0.465 (P = 0.001). The surgery group had
      significantly better 5-year cause-specific survival (80.5% vs 59.1%; P = 0.001)
      and overall survival than the nonsurgery group (76.3% vs 56.0%; P = 0.002).
      CONCLUSIONS: Additional adjuvant hysterectomy after radiochemotherapy may improve
      survival outcomes in patients with FIGO stage I-II cervical adenocarcinoma.

PMID- 30114329
TI  - Immediate lymphatic reconstruction.
AB  - Although surgical and medical treatment options are available for the treatment
      of chronic lymphedema, there is no cure. Recent advances in microsurgery have
      provided an opportunity to perform immediate lymphatic reconstruction after
      lymphadenectomy for disease prevention. In this review, we provide the historical
      background leading to a paradigm shift in performing this procedure. We will also
      discuss the current evidence for immediate lymphatic reconstruction, potential
      oncologic procedures amenable to this approach, and detail ongoing challenges.

PMID- 30114330
TI  - Impact of neoadjuvant therapy on postoperative outcomes after
      pancreaticoduodenectomy.
AB  - BACKGROUND: Surgical resection provides the only potentially curative treatment
      of pancreatic cancer. Neoadjuvant chemotherapy and/or radiation (NAT) is used to
      downstage patients with borderline resectable tumors. The objective of this study
      was to examine the postoperative morbidity and mortality of NAT after
      pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDA). METHODS:
      Using the American College of Surgeons-National Surgical Quality Improvement
      Project Targeted Pancreatectomy data, we identified patients who underwent a PD
      for PDA from 2014 to 2015. Patients were grouped by receipt of NAT 90 days before
      PD. Bivariable and multivariable analyses was used to compare postoperative
      outcomes. RESULTS: A total of 3748 patients with PDA underwent PD; 926 (24.7%)
      received NAT. Those in the NAT group had more major vein resections, and longer
      operating times (all P < 0.001). On pathologic staging, those in the NAT group
      had smaller tumors (T1, 10.9% vs 5.1%; P < 0.001) and fewer nodes positive (N0,
      49% vs 28%; P < 0.001). There were no differences in 30-day postoperative
      mortality or overall complications. On multivariable analysis, patients who
      received NAT had a lower likelihood of pancreatic fistula (OR, 0.67; P < 0.001).
      CONCLUSION: NAT does not increase the overall postoperative morbidity or
      mortality of PD for PDA. There is a decreased likelihood of pancreatic fistulas
      in patients that receive neoadjuvant therapy.

PMID- 30114331
TI  - Expression of Hbs, Kirre, and Rst during Drosophila ovarian development.
AB  - The Irre cell-recognition module (IRM) is a group of evolutionarily conserved and
      structurally related transmembrane glycoproteins of the immunoglobulin
      superfamily. In Drosophila melanogaster, it comprises the products of the genes
      roughest (rst; also known as irreC-rst), kin-of-irre (kirre; also known as duf),
      sticks-and-stones (sns), and hibris (hbs). In this model organism, the behavior
      of this group of proteins as a partly redundant functional unit mediating
      selective cell recognition was demonstrated in a variety of developmental
      contexts, but their possible involvement in ovarian development and oogenesis has
      not been investigated, notwithstanding the fact that some rst mutant alleles are
      also female sterile. Here, we show that IRM genes are dynamically and, to some
      extent, coordinately transcribed in both pupal and adult ovaries. Additionally,
      the spatial distribution of Hbs, Kirre, and Rst proteins indicates that they
      perform cooperative, although largely nonredundant, functions. Finally,
      phenotypical characterization of three different female sterile rst alleles
      uncovered two temporally separated and functionally distinct requirements for
      this locus in ovarian development: one in pupa, essential for the organization of
      peritoneal and epithelial sheaths that maintain the structural integrity of the
      adult organ and another, in mature ovarioles, needed for the progression of
      oogenesis beyond stage 10.

PMID- 30114332
TI  - Ergonomics in microsurgery.
AB  - There is a growing body of evidence to suggest that surgeon posture while
      operating contributes to cervical musculoskeletal strain, discomfort, and chronic
      pain. Microsurgeons may be particularly susceptible to this risk due to
      persistent neck flexion, long periods of static posture, and the use of heavy,
      high-power loupe magnification. Several techniques are thus presented that may
      help in obviating the cervicospinal repercussions of performing microsurgery.

PMID- 30114333
TI  - The prognostic value of serum thyroid-stimulating hormone level post-lobectomy in
      low- and intermediate-risk papillary thyroid carcinoma.
AB  - BACKGROUND: This study was undertaken to determine the optimal thyroid
      stimulating hormone (TSH) value associated with structural recurrence in patients
      with low-risk or intermediate-risk papillary thyroid carcinoma (PTC) who
      underwent thyroid lobectomy. METHODS: Patients with PTC (n = 1047) who received
      thyroid lobectomy and central compartment node dissection were included in the
      study. RESULTS: Structural recurrence occurred in 42 of the patients (4.0%), and
      no patient died of PTC. Multivariate analysis showed a primary tumor size (with a
      cut-off of 0.85 cm) and serum TSH level measured 1 year after the initial surgery
      (cut-off 1.85 mU/L) independently predicted structural recurrence. CONCLUSIONS:
      TSH levels during the early postoperative period need to be monitored and
      maintained in the lower normal range even in patients with low- or intermediate
      risk PTC undergoing thyroid lobectomy.

PMID- 30114334
TI  - A gene regulatory network anchored by LIM homeobox 1 for embryonic head
      development.
AB  - Development of the embryonic head is driven by the activity of gene regulatory
      networks of transcription factors. LHX1 is a homeobox transcription factor that
      plays an essential role in the formation of the embryonic head. The loss of LHX1
      function results in anterior truncation of the embryo caused by the disruption of
      morphogenetic movement of tissue precursors and the dysregulation of WNT
      signaling activity. Profiling the gene expression pattern in the Lhx1 mutant
      embryo revealed that tissues in anterior germ layers acquire posterior tissue
      characteristics, suggesting LHX1 activity is required for the allocation and
      patterning of head precursor tissues. Here, we used LHX1 as an entry point to
      delineate its transcriptional targets and interactors and construct a LHX1
      anchored gene regulatory network. Using a gain-of-function approach, we
      identified genes that immediately respond to Lhx1 activation. Meta-analysis of
      the datasets of LHX1-responsive genes and genes expressed in the anterior tissues
      of mouse embryos at head-fold stage, in conjunction with published Xenopus
      embryonic LHX1 (Xlim1) ChIP-seq data, has pinpointed the putative transcriptional
      targets of LHX1 and an array of genetic determinants functioning together in the
      formation of the mouse embryonic head.

PMID- 30114335
TI  - Robotic (super) microsurgery: Feasibility of a new master-slave platform in an in
      vivo animal model and future directions.
AB  - Advanced microsurgical procedures are currently limited by human precision and
      manual dexterity. The potential of robotics in microsurgery is highlighted,
      including a general overview of applications of robotic assistance in
      microsurgery and its introduction in different surgical specialties. A new
      robotic platform especially designed for (super) microsurgery is presented.
      Results of an in vivo animal study underline its feasibility and encourage
      further development toward clinical studies. Future directions of robotic
      microsurgery are proposed.

PMID- 30114336
TI  - PROMIS(r) scores in operative metastatic bone disease patients: A multicenter,
      prospective study.
AB  - BACKGROUND: The prevalence of metastatic bone disease (MBD) grows each year as
      treatments improve. Little has been published about functional and pain outcomes
      in this group after surgery. Patient-Reported Outcomes Measurement Information
      System (PROMIS(r) ) can collect information, in just minutes, about patient's
      physical, mental, and social health. This study evaluated PROMIS(r) pain and
      functional scores in surgically treated patients with MBD. METHODS: Basic
      demographics and PROMIS(r) scores were recorded from a total of 13 patients at 9
      periods of time over 6 months. RESULTS: The average change in physical function
      at week 1 was -2.5 (standard deviation [SD] = 5.4), at 2 weeks 1.7 (SD = 7.6),
      after 4 weeks 6.9 (SD = 10), after 6 weeks 6.4 (SD = 10.9), after 10 weeks 15.3
      (SD = 3.1), and after 3 months 8.6 (SD = 7.6). The average change in pain
      inference at week 1 was -1.2 (SD = 7.3), at 2 weeks -2.1 (SD = 9.5), after 4
      weeks -12.6 (SD = 4.5), after 6 weeks -8.3 (SD = 10.2), after 10 weeks -16.6 (SD
      = 4.3), and after 3 months -11.4 (SD = 8.2). CONCLUSIONS: PROMIS(r) provides a
      feasible means to collect data in this population. Trends of improved function
      and decreased pain were seen after surgery. Continuing this study will hopefully
      elucidate more insight into the surgical treatment of MBD.

PMID- 30114337
TI  - Patterns of failure following the excision of in-transit lesions in melanoma and
      the influence of excisional margins.
AB  - BACKGROUND AND OBJECTIVES: To describe the patterns of failure in patients with
      in-transit (IT) melanoma undergoing surgical excision. METHODS: A retrospective
      review of patients who underwent their first IT lesion(s) resection between May
      2005 and September 2014. Cumulative incidence of local failure (new lesion within
      2 cm of IT resection) was estimated. Associations between clinicopathologic
      characteristics, local failure, and any recurrence were analyzed. RESULTS: One
      hundred and thirty patients presented to our institution with IT disease over the
      study period and met the inclusion criteria. The 2-year cumulative incidence of
      local failure was 19.5%. Twenty-four patients developed disease within 2 cm of
      the resected IT disease; however, only eight were isolated local events.
      Cumulative incidence of local failure and of any disease differed with respect to
      less than 1 year disease-free interval (DFI) from primary melanoma to first IT
      event, and having greater than 1 IT lesion at presentation. Incidence of local
      failure was not found to differ with respect to gross margin greater than 5 mm,
      after adjusting for DFI and greater than 1 IT lesions. CONCLUSIONS: Patients with
      greater than 1 IT lesion and a DFI less than 1 year are at a higher risk of
      failure after surgical excision of a first IT event. Very few failures were
      isolated local disease within 2 cm of the IT resection scar, regardless of IT
      excision margin.

PMID- 30114338
TI  - Measuring Subjective Probabilities: The Effect of Response Mode on the Use of
      Focal Responses, Validity, and Respondents' Evaluations.
AB  - Subjective probabilities are central to risk assessment, decision making, and
      risk communication efforts. Surveys measuring probability judgments have
      traditionally used open-ended response modes, asking participants to generate a
      response between 0% and 100%. A typical finding is the seemingly excessive use of
      50%, perhaps as an expression of "I don't know." In an online survey with a
      nationally representative sample of the Dutch population, we examined the effect
      of response modes on the use of 50% and other focal responses, predictive
      validity, and respondents' survey evaluations. Respondents assessed the
      probability of dying, getting the flu, and experiencing other health-related
      events. They were randomly assigned to a traditional open-ended response mode, a
      visual linear scale ranging from 0% to 100%, or a version of that visual linear
      scale on which a magnifier emerged after clicking on it. We found that, compared
      to the open-ended response mode, the visual linear and magnifier scale each
      reduced the use of 50%, 0%, and 100% responses, especially among respondents with
      low numeracy. Responses given with each response mode were valid, in terms of
      significant correlations with health behavior and outcomes. Where differences
      emerged, the visual scales seemed to have slightly better validity than the open
      ended response mode. Both high-numerate and low-numerate respondents' evaluations
      of the surveys were highest for the visual linear scale. Our results have
      implications for subjective probability elicitation and survey design.

PMID- 30114339
TI  - Dynamic risk stratification in papillary thyroid carcinoma measuring 1 to 4 cm.
AB  - BACKGROUND AND OBJECTIVES: This study aimed to validate the dynamic risk
      stratification (DRS) system, evaluate its correlation with structural recurrence,
      and assess the clinicopathological risk factors associated with a nonexcellent
      response to initial therapy in patients with papillary thyroid cancer (PTC)
      measuring 1 to 4 cm. METHODS: A total of 762 patients with classic PTC measuring
      1 to 4 cm were classified into four categories based on their response to initial
      therapy 2 years postoperatively. RESULTS: Structural recurrent disease occurred
      in 4.7%, 17.1%, 48.4%, and 83.9% of patients with excellent, indeterminate,
      biochemically incomplete, and structurally incomplete responses, respectively, at
      the time of the last follow-up. The response to initial therapy in the DRS was
      one of the independent risk factors for structural recurrence. The disease-free
      survival curves of patients with different responses showed significant
      differences (P < 0.001). Extensive extrathyroidal extension, lymph node (LN)
      metastasis, number of metastatic LNs greater than 2.0, metastatic LN ratio
      greater than 0.22, and extranodal extension were independent risk factors for
      nonexcellent response to initial therapy. CONCLUSIONS: DRS can be a useful tool
      in predicting structural recurrence and guiding postoperative management and
      follow-up strategies in patients with PTC measuring 1 to 4 cm.

PMID- 30114340
TI  - Mutational analysis of CCL20 reveals flexibility of N-terminal amino acid
      composition and length.
AB  - Chemokine-chemokine receptor (CKR) interactions are traditionally described by a
      two-step/two-site mechanism that details the major contact points between
      chemokine ligands and CKRs leading to ligand recognition and receptor activation.
      Chemokine recognition site 1 (CRS1) encompasses interactions between the CKR N
      terminus and the globular chemokine core. Chemokine recognition site 2 (CRS2)
      includes interactions between the unstructured chemokine N-terminus and the
      binding pocket of the receptor. The two-step/two-site paradigm has been an
      adequate framework to study the intricacies of chemokine:CKR interactions, but
      emerging studies highlight the limitations of this model. Here, we present
      studies of CRS2 interactions between the chemokine CCL20 and its cognate receptor
      CCR6 driven by the hypothesis that CCL20 interacts with CCR6 as described by the
      two-step/two-site model. CCL20 is a chemokine with an unusually short N-terminus
      of 5 residues (NH2 -ASNFD), compared to the average length of 10 residues for
      chemokine ligands. We have investigated how well CCL20 tolerates manipulation of
      the N-terminus by monitoring binding affinity of variants and their ability to
      activate the receptor. We show the CCL20 N-terminus tolerates truncation of up to
      3 residues, extension by up to 5 additional residues, and point mutations at 4 of
      5 positions with minimal loss of binding affinity and minimal impairment in
      ability to stimulate calcium mobilization, inositol triphosphate accumulation,
      chemotaxis, and beta-arrestin-2 recruitment. Mutation of the fifth residue,
      aspartate, to alanine or lysine has a dramatic impact on binding affinity for
      CCR6 and ligand potency. We postulate CCL20 does not activate CCR6 through the
      canonical two-step/two-site mechanism of CKR activation.

PMID- 30114341
TI  - Comprehensive Insight into the Hydrogen Bonding of Silanes.
AB  - The interaction of a set of mono-, di- and trisubstituted silanes with OH proton
      donors of different strength was studied by variable temperature (VT) FTIR and
      NMR spectroscopies at 190-298 K. Two competing sites of proton donors
      coordination: SiH and pi-density of phenyl rings-are revealed for phenyl
      containing silanes. The hydrogen bonds SiH???HO and OH???pi(Ph) are of similar
      strength, but can be distinguished in the nuSiH range: the nuSiH???HO vibrations
      appear at lower frequencies while OH???pi(Ph) complexes give Si-H vibrations
      shifted to higher frequency. The calculations showed the manifold picture of the
      noncovalent interactions in hydrogen-bonded complexes of phenylsilanes. As
      OH???HSi bonds are weak, the other noncovalent interactions compete in the
      stabilization of the intermolecular complexes. Still, the structural and
      electronic parameters of "pure" DHB complexes of phenylsilanes are similar to
      those of Et3 SiH.

PMID- 30114342
TI  - In Situ Imaging of Tryptic Peptides by MALDI Imaging Mass Spectrometry Using
      Fresh-Frozen or Formalin-Fixed, Paraffin-Embedded Tissue.
AB  - Tryptic peptide imaging is a primary workflow for matrix-assisted laser
      desorption/ionization imaging mass spectrometry (MALDI IMS) and has led to new
      information reporting highly multiplexed protein localization. Technological
      advances within the last few years have produced robust tools for automated
      spraying of both matrix and enzymes. When combined with high-mass-resolution and
      high-mass-accuracy instrumentation, studies now generally result in two
      dimensional mapping of well over 1,000 peptide peaks. This protocol describes
      sample preparation, spraying, and application of enzymes and matrices, and MALDI
      FT-ICR instrumental considerations for two-dimensional mapping of tryptic
      peptides from fresh-frozen or formalin-fixed, paraffin-embedded tissue sections.
      Procedures for extraction of tryptic peptides from tissue sections for LC-MS/MS
      identification are also described. (c) 2018 by John Wiley & Sons, Inc.

PMID- 30114343
TI  - Heart rate mean and variability as a biomarker for phenotypic variation in
      preschoolers with autism spectrum disorder.
AB  - : Interest in autonomic arousal in autism spectrum disorder (ASD) is increasing;
      however, reliability of these measures in ASD is unknown, and previously reported
      associations with social and cognitive abilities are inconsistent. This study
      assesses heart rate (HR) and HR variability (HRV) in preschoolers with ASD or
      typical development (TD) while they passively watched naturalistic videos.
      Measurement reliability, group differences, and the relationship with social and
      cognitive abilities were evaluated. Seventy one ASD and 66 TD children (2-4
      years) provided cardiac data from two sessions. Test-retest intraclass
      correlations of HR and HRV over a 3-week period were moderate to good in both
      groups. Groups did not differ in mean level of HR or HRV. Intra-individual
      variability of HR between video segments within a session was higher in the ASD
      group, but intraclass correlations of this metric were low. Higher HR related to
      better language skills in TD children, but not after accounting for age and
      nonverbal ability. Higher HRV related to better expressive and receptive language
      in ASD children after controlling for age and nonverbal ability. HR/HRV were not
      related to social or executive functioning skills and did not explain any
      additional variance in abilities at a 12-month follow-up visit. In summary,
      variation in language abilities is associated with HR in the TD group and HRV in
      the ASD group. While preliminary, these results are promising for consideration
      of autonomic control as a biomarker for individual differences in ASD and may
      help us understand the mechanisms that contribute to communication skills. LAY
      SUMMARY: Cardiac activity, such as heart rate and heart rate variability, is
      linked to a wide range of psychological functions. This study shows that there is
      an association between heart rate and heart rate variability and language skills
      in young children with autism spectrum disorder (ASD). These results may help us
      understand what underlies individual differences in developmental abilities in
      young children with ASD.

PMID- 30114344
TI  - Alterations in hub organization in the white matter structural network in
      toddlers with autism spectrum disorder: A 2-year follow-up study.
AB  - Little is currently known about the longitudinal developmental patterns of hubs
      in the whole-brain white matter (WM) structural networks among toddlers with
      autism spectrum disorder (ASD). This study utilized diffusion tensor imaging
      (DTI) and deterministic tractography to map the WM structural networks in 37 ASD
      toddlers and 27 age-, gender- and developmental quotient-matched controls with
      developmental delay (DD) toddlers aged 2-3 years old at baseline (Time 1) and at
      2-year follow-up (Time 2). Furthermore, graph-theoretical methods were applied to
      investigate alterations in the network hubs in these patients at the two time
      points. The results showed that after 2 years, 17 hubs were identified in the ASD
      subjects compared to the controls, including 13 hubs that had not changed from
      baseline and 4 hubs that were newly identified. In addition, alterations in the
      properties of the hubs of the right middle frontal gyrus, right insula, left
      median cingulate gyri, and bilateral precuneus were significantly correlated with
      alterations in the behavioral data for ASD patients. These results indicated that
      at the stage of 2-5 years of age, ASD children showed distributions of network
      hubs that were relatively stable, with minor differences. Abnormal developmental
      patterns in the five areas mentioned above in ASD may contribute to abnormalities
      in the social and nonsocial characteristics of this disorder. Autism Res 2018,
      11: 1218-1228. (c) 2018 International Society for Autism Research, Wiley
      Periodicals, Inc. LAY SUMMARY: This work studied the longitudinal developmental
      patterns of hubs in the whole-brain white matter (WM) structural network among
      toddlers with autism spectrum disorder (ASD). The findings of this study could
      have implications for understanding how the abnormalities in hub organization in
      ASD account for behavioral deficits in patients and may provide potential
      biomarkers for disease diagnosis and the subsequent monitoring of progression and
      treatment effects for patients with ASD.

PMID- 30114345
TI  - Folic acid, dietary habits, and homocysteine levels in relation to neural tube
      defects: A case-control study in North India.
AB  - PURPOSE: The present study attempts to understand the complex contribution of
      biochemical (plasma homocysteine) and nutritional parameters (dietary pattern and
      folate supplementation) to the neural tube defects (NTDs) affected pregnancies
      and controls in North Indian population. METHODS: Case-control study design was
      adopted to assess the role of folic acid, dietary habits, and homocysteine in
      relation to NTD births. The subjects comprised of 130 mothers of affected
      children (cases) and 233 mothers of healthy children (controls), who were either
      carrying NTD fetus or gave birth to NTD child. RESULTS: The mean homocysteine
      levels were elevated in cases (15.71 +/- 8.35 MUmol/L) as compared to controls
      (12.87 +/- 5.95 MUmol/L) but were lower among the non-vergetarians (13.55 +/-
      6.64 MUmol/L) than the vegetarians (14.78 +/- 7.93 MUmol/L). Vegetarian dietary
      habit increased the NTD risk by 1.6 fold (95% CI = 1.0-2.7) while folic acid
      supplementation demonstrated a protective effect for conceptions (OR = 0.59; 95%
      CI = 0.3-0.9). Consumption of folic acid with non-vegetarian diet witnessed
      lowering of homocysteine in cases (12.88 +/- 6.81 MUmol/L) and in controls (11.85
      +/- 5.54 MUmol/L), with an odds ratio depicting a 3.1 fold risk for consuming
      vegetarian diet without folic acid supplementation during the peri-conceptional
      period. CONCLUSION: It is suggested that plasma hyperhomocysteinemia bears
      negative impact on child-bearing women group, of north Indian ancestry, in
      modulating the risk of NTDs. Efforts should be made to enhance awareness
      regarding folic acid and vitamin B12 (non-vegetarian diet) supplementations
      alongwith proper nutritional intake among women, especially those consuming
      vegetarian diet to control homocysteine levels in order to reduce the risk of
      NTDs.

PMID- 30114346
TI  - CBP/p300 inhibitor C646 prevents high glucose exposure induced neuroepithelial
      cell proliferation.
AB  - BACKGROUND: Maternal diabetes related neural tube defects (NTDs) are a result of
      oxidative stress and apoptosis. However, the molecular mechanism behind the
      pathogenesis is not fully understood. Here, we report that high glucose exposure
      induced epigenetic changes influence histone H4 acetylation and neuroepithelial
      cell proliferation. We also show that the acetyltransferase inhibitor C646 can
      prevent high glucose induced changes in histone H4 acetylation and
      neuroepithelial cell proliferation. METHODS: By using LC-MS/MS as an unbiased
      approach, we screened the histone acetylation profile in an E9 neuroepithelial
      cell line (NE-4C) under high glucose exposure. We further explored the mechanism
      in cells in vitro and in maternal diabetes-induced mouse embryos in vivo.
      RESULTS: We identified 35 core histone acetylation marks in normal E9
      neuroepithelial cells, whereas high glucose exposure resulted in novel
      acetylation sites on H4K31 and H4K44. Acetylation levels of embryonic development
      associated H4K5/K8/K12/K16 increased in neuroepithelial cells exposed to high
      glucose in vitro and in brain tissue from maternal diabetes induced exencephalic
      embryos in vivo. Further, mRNA level of histone acetyltransferase CBP encoded
      gene Crebbp was significantly increased both in vitro and in vivo. The addition
      of C646, a selective inhibitor for CBP/p300, significantly rescued increase of
      H4K5/K8/K12/K16 acetylation levels and H3S10pi-labeled neuroepithelial cell
      proliferation induced by high glucose exposure. CONCLUSION: Our data provide
      complementary insights for potential mechanisms of maternal diabetes induced
      NTDs.

PMID- 30114347
TI  - Takayasu arteritis: an update
AB  - Takayasu arteritis (TAK) is a challenging chronic, granulomatous, large-vessel
      systemic vasculitis, mostly due to difficulties in early diagnosis and assessing
      actual disease activity. Since there are no specific diagnostic laboratory tests,
      biomarkers, or autoantibodies, many patients experience considerable delay in
      diagnosis. Remembering the possibility of TAK together with the use of acute
      phase responses and appropriate imaging studies may be helpful for early
      diagnosis. Since there may be discrepancies between systemic and vascular  wall 
      inflammation,  using  only  acute  phase  responses  is  not  reliable  in 
      assessing  current  disease  activity.  Therefore,  physical  examination and new
      imaging findings should also be used to assess current disease activity. Despite
      its limitations, the Indian Takayasu Clinical Activity Score (ITAS2010) may also
      be helpful for this purpose. The rationale of medical treatment is to suppress
      both vascular and systemic inflammation with appropriate systemic
      immunosuppression, including corticosteroids and conventional immunosuppressive
      agents.  In  cases  of  refractory  disease  activity,  leflunomide  and 
      biologic  agents  such  as  TNF  inhibitors  and  tocilizumab  may  be  tried. 
      In selected cases with persistent lesions that cannot be reversed with medical
      treatment, endovascular interventions including balloon angioplasty, stent and
      stent graft replacement, or surgery may be tried. However, such procedures should
      be performed after suppression of inflammation, i.e. during inactive disease.
      Prognosis of TAK is probably getting better with lower mortality rates reported
      in recent years, probably due to the use of more effective medical treatments as
      well as the use of endovascular interventions when necessary and available.

PMID- 30114348
TI  - Polycythemia vera: diagnosis, clinical course, and current management
AB  - Very important developments related to polycythemia vera (PV) have occurred
      during the last two decades. The discovery of Janus kinase (JAK) 2 mutations has
      changed both the diagnosis and clinical management of PV. Currently JAK2
      molecular testing is essential in the diagnostic work-up and JAK2 mutation
      positivity is a major diagnostic criterion. The discovery of JAK2 mutations
      suggested  that  abnormal  JAK-STAT  signaling  was  a  pivotal  feature  in  the
      pathogenesis  of  Philadelphia-negative  myeloproliferative  neoplasms. This
      idea led to the development of JAK inhibitors. Currently ruxolitinib, a JAK1/JAK2
      inhibitor, is also approved for PV patients with hydroxyurea resistance or
      intolerance. International collaborations have made it possible to describe
      disease characteristics and evolution better. Presently it is possible to
      quantify the symptomatic burden of the disease and to estimate prognosis. In
      spite of these  developments,  management  of  PV  still  largely  depends  on 
      estimation  of  thromboembolic  risk  and  trying  to  decrease  the  risk  with
      or without cytoreductive medications. Different approaches have been proposed by
      international disease experts for the diagnosis, thromboembolic  risk 
      estimation,  and  drug  selection.  This  paper  aims  to  review  clinical 
      aspects  of  PV  and  propose  a  management  algorithm. The authors also point
      to still unresolved questions and unmet needs in diagnosis and management.

PMID- 30114349
TI  - Comparison between laparoscopy and laboratory tests for the diagnosis of
      tuberculous peritonitis
AB  - Background/aim: Our study aimed to investigate a reliable diagnostic approach for
      tuberculous peritonitis (TBP) by comparing the commonly used diagnostic tools.
      Materials and methods: Fifty-one patients had received a series of diagnoses,
      including laparoscopy, erythrocyte sedimentation rate (ESR), cancer antigen 125
      (CA125), tuberculin skin test, tuberculosis antibody in serum (TB-Ab), the T
      SPOT.TB test, or adenosine deaminase  (ADA)  in  ascitic  fluid.  The  positive 
      rate  of  each  method  was  calculated  and  the  differences  of  positive 
      rates  between  laparoscopy and laboratory tests that had higher positive rates
      were analyzed by McNemar chi-square test. Results: The  most  common  symptoms 
      and  signs  of  51  patients  were  fever  (86.3%),  abdominal  mass  (78.4%), 
      abdominal  distension  (62.7%), abdominal pain (74.5%), and weight loss (66.7%).
      Furthermore, the positive rates of CA125, laparoscopy, T-SPOT.TB test, and ESR
      were relatively higher than those of the other three methods (tuberculin skin
      test, TB-Ab, and ascitic ADA). Additionally, there was no significant difference
      (P > 0.05) in the positive rates between the diagnoses of laparoscopy and those
      three laboratory tests. Conclusion: CA125, laparoscopy, T-SPOT.TB test, and ESR
      had a stronger diagnostic power for TBP, and they are reliable alternatives for
      the diagnosis of TBP.

PMID- 30114350
TI  - Ultra Gas-Proof Polymer Hybrid Thin Layer.
AB  - Hermetic sealing is an important technology for isolating and protecting air
      sensitive materials and is key in the development of foldable and stretchable
      electronic devices. Here we report an ultra gas-proof polymer hybrid thin layer
      prepared by filling the free volume of the polymer with Al2O3 using gas-phase
      atomic layer infiltration. The high-density polymer-inorganic hybrid shows
      extremely low gas transmission rate, below the detection limit of the Ca
      corrosion test (water vapor transmission rate <10-7 g m-2 day-1). Furthermore,
      because of the remarkable nanometer-scale thinness of the complete polymer
      inorganic hybrid, it is highly flexible, which makes it useful for hermetic
      sealing of stretchable and foldable devices.

PMID- 30114351
TI  - Targeted Therapy of Atherosclerosis by a Broad-Spectrum Reactive Oxygen Species
      Scavenging Nanoparticle with Intrinsic Anti-inflammatory Activity.
AB  - Atherosclerosis is a leading cause of vascular diseases worldwide. Whereas
      antioxidative therapy has been considered promising for the treatment of
      atherosclerosis in view of a critical role of reactive oxygen species (ROS) in
      the pathogenesis of atherosclerosis, currently available antioxidants showed
      considerably limited clinical outcomes. Herein, we hypothesize that a broad
      spectrum ROS-scavenging nanoparticle can serve as an effective therapy for
      atherosclerosis, taking advantage of its antioxidative stress activity and
      targeting effects. As a proof of concept, a broad-spectrum ROS-eliminating
      material was synthesized by covalently conjugating a superoxide dismutase mimetic
      agent Tempol and a hydrogen-peroxide-eliminating compound of phenylboronic acid
      pinacol ester onto a cyclic polysaccharide beta-cyclodextrin (abbreviated as
      TPCD). TPCD could be easily processed into a nanoparticle (TPCD NP). The obtained
      nanotherapy TPCD NP could be efficiently and rapidly internalized by macrophages
      and vascular smooth muscle cells (VSMCs). TPCD NPs significantly attenuated ROS
      induced inflammation and cell apoptosis in macrophages, by eliminating
      overproduced intracellular ROS. Also, TPCD NPs effectively inhibited foam cell
      formation in macrophages and VSMCs by decreasing internalization of oxidized low
      density lipoprotein. After intravenous (i.v.) administration, TPCD NPs
      accumulated in atherosclerotic lesions of apolipoprotein E-deficient (ApoE-/-)
      mice by passive targeting through the dysfunctional endothelium and translocation
      via inflammatory cells. TPCD NPs significantly inhibited the development of
      atherosclerosis in ApoE-/- mice after i.v. delivery. More importantly, therapy
      with TPCD NPs afforded stabilized plaques with less cholesterol crystals, a
      smaller necrotic core, thicker fibrous cap, and lower macrophages and matrix
      metalloproteinase-9, compared with those treated with control drugs previously
      developed for antiatherosclerosis. The therapeutic benefits of TPCD NPs mainly
      resulted from reduced systemic and local oxidative stress and inflammation as
      well as decreased inflammatory cell infiltration in atherosclerotic plaques.
      Preliminary in vivo tests implied that TPCD NPs were safe after long-term
      treatment via i.v. injection. Consequently, TPCD NPs can be developed as a
      potential antiatherosclerotic nanotherapy.

PMID- 30114352
TI  - Triboelectric Nanogenerators Made of Porous Polyamide Nanofiber Mats and
      Polyimide Aerogel Film: Output Optimization and Performance in Circuits.
AB  - Triboelectric nanogenerators (TENGs) have been attracting a tremendous amount of
      attention since their discovery in 2012. Finding new means to enhance energy
      output is an ongoing pursuit. Herein, we introduce a new type of high-performance
      TENG composed of highly porous polyamide (PA) nanofiber mats and polyimide
      aerogel films. We have demonstrated that the thickness of the porous
      triboelectric materials, which is attained by stacking multiple layers of
      triboelectric materials, has a profound effect on the triboelectric output
      performance of TENGs. The triboelectric output increased when PA increased from
      one layer to six layers. However, it decreased when PA was further increased to
      12 layers. With an optimum material thickness, a TENG with only a 2 cm2 effective
      device size achieved a high output voltage of 115 V and a current of 9.5 MUA
      under a small compressive pressure (30 kPa). A peak power density of 1.84 W/m2
      was achieved on a 4.7 MOmega external load. The TENG was able to light 60 light
      emitting diodes easily and quickly charge capacitors with different capacitance
      to 6 V, indicating an outstanding energy harvesting ability. In addition, the
      performance of multiple TENGs connected in different ways, as well as the
      performance of TENGs in resistive/inductive/capacitive circuits, were
      investigated. These findings provide new insight into the working principles of
      TENGs in complex circuits.

PMID- 30114355
TI  - Versatile Cobalt-Catalyzed Enantioselective Entry to Boryl-Functionalized All
      Carbon Quaternary Stereogenic Centers.
AB  - We report an asymmetric synthesis of chiral boryl-functionalized gamma-lactams
      containing all-carbon quaternary stereocenters via a Co-catalyzed
      enantioselective hydroboration/cyclization of amide-tethered 1,6-enynes. These
      enantio-enriched gamma-lactam products can be readily converted to a variety of
      cyclic and acyclic other chiral gamma-lactams, pyrrolidin-2,3-diones, beta-amino
      acid N-carboxyanhydrides, and beta-amino carboxylic amides.

PMID- 30114354
TI  - Patterning-Induced Ferromagnetism of Fe3GeTe2 van der Waals Materials beyond Room
      Temperature.
AB  - Magnetic van der Waals (vdW) materials have emerged as promising candidates for
      spintronics applications, especially after the recent discovery of intrinsic
      ferromagnetism in monolayer vdW materials. There has been a critical need for
      tunable ferromagnetic vdW materials beyond room temperature. Here, we report a
      real-space imaging study of itinerant ferromagnet Fe3GeTe2 and the enhancement of
      its Curie temperature well above ambient temperature. We find that the magnetic
      long-range order in Fe3GeTe2 is characterized by an unconventional out-of-plane
      stripe-domain phase. In Fe3GeTe2 microstructures patterned by a focused ion beam,
      the out-of-plane stripe domain phase undergoes a surprising transition at 230 K
      to an in-plane vortex phase that persists beyond room temperature. The discovery
      of tunable ferromagnetism in Fe3GeTe2 materials opens up vast opportunities for
      utilizing vdW magnets in room-temperature spintronics devices.

PMID- 30114353
TI  - Structure-Function Analyses of the N-Butanoyl l-Homoserine Lactone Quorum-Sensing
      Signal Define Features Critical to Activity in RhlR.
AB  - Pseudomonas aeruginosa is an opportunistic pathogen that coordinates the
      production of many virulence phenotypes at high population density via quorum
      sensing (QS). The LuxR-type receptor RhlR plays an important role in the P.
      aeruginosa QS process, and there is considerable interest in the development of
      chemical approaches to modulate the activity of this protein. RhlR is activated
      by a simple, low molecular weight N-acyl l-homoserine lactone signal, N-butanoyll
      homoserine lactone (BHL). Despite the emerging prominence of RhlR in QS pathways,
      there has been limited exploration of the chemical features of the BHL scaffold
      that are critical to its function. In the current study, we sought to
      systematically delineate the structure-activity relationships (SARs) driving BHL
      activity for the first time. A focused library of BHL analogues was designed,
      synthesized, and evaluated in cell-based reporter gene assays for RhlR agonism
      and antagonism. These investigations allowed us to define a series of SARs for
      BHL-type ligands and identify structural motifs critical for both activation and
      inhibition of the RhlR receptor. Notably, we identified agonists that have ~10
      fold higher potencies in RhlR relative to BHL, are highly selective for RhlR
      agonism over LasR, and are active in the P. aeruginosa background. These
      compounds and the SARs reported herein should pave a route toward new chemical
      strategies to study RhlR in P. aeruginosa.

PMID- 30114356
TI  - Surface-Functionalized Model Contact Lenses with a Bioinspired Proteoglycan 4
      (PRG4)-Grafted Layer.
AB  - Ocular dryness and discomfort are the primary reasons for the discontinuation of
      contact lens wear. This is mainly due to poorly hydrated contact lens surfaces
      and increased friction, particularly at the end of the day and can potentially
      cause reduced vision or even inflammation. Proteoglycan 4 (PRG4) is a mucinous
      glycoprotein with boundary lubricating properties, naturally found in the eye,
      able to prevent tear film evaporation and protect the ocular surface during
      blinking. Aiming to improve the interfacial interactions between the ocular
      surface and the contact lens, the synthesis and characterization of surface
      modified model contact lenses with PRG4 is described. Full-length recombinant
      human PRG4 (rhPRG4) was successfully grafted onto the surface of model
      conventional and silicone hydrogel (SiHy) contact lenses via its somatomedin B
      like end-domain using N, N'-carbonyldiimidazole linking chemistry. Grafting was
      assessed by Fourier transform infrared spectroscopy-attenuated total reflectance,
      X-ray photoelectron spectroscopy, and radioactive (I131) labeling. Surface
      immobilization of rhPRG4 led to model conventional and SiHy materials with
      improved antifouling properties, without impacting optical transparency or
      causing any toxic effects to human corneal epithelial cells in vitro. The surface
      wettability and the boundary friction against human corneal tissue were found to
      be substrate-dependent, with only the rhPRG4-grafted model SiHy exhibiting a
      reduced contact angle and kinetic friction coefficient compared to the unmodified
      surfaces. Hence, clinical grade rhPRG4 can be an attractive candidate for the
      development of novel bioinspired SiHy contact lenses, providing improved comfort
      and overall lens performance.

PMID- 30114357
TI  - Quantifying the Kinetic Residence Time as a Potential Complement to Affinity for
      the Aptamer Selection.
AB  - Aptamers have been widely developed for biotechnological and therapeutic
      applications in recent years. Increasing evidence shows that the quality of the
      aptamer is determined not only by the thermodynamic stability but also by the
      kinetic residence time when binding with its target. However, both experimental
      and computational selection methods of aptamers concentrate solely on the binding
      affinity optimization. Here, we propose a computational method for the
      quantification of the residence time by describing the kinetics on the underlying
      funneled binding energy landscape of aptamer-target complex as a diffusion
      process. The quantified residence time is examined to have the capacity to
      discriminate native aptamer-target complexes against non-native ones. It is found
      that the residence time is correlated with the binding affinity but with
      significant dispersion, suggesting that the residence time can be a potential
      complement in selecting the aptamer. On the basis of the results, a two
      dimensional selection method with both the thermodynamic binding affinity and the
      residence time as kinetic specificity is suggested for diverse applications of
      aptamers. This alters conventional aptamer selection methods by considering the
      kinetic residence time in addition to the affinity.

PMID- 30114359
TI  - Improved Peptide Retention Time Prediction in Liquid Chromatography through Deep
      Learning.
AB  - The accuracy of peptide retention time (RT) prediction model in liquid
      chromatography (LC) is still not sufficient for wider implementation in
      proteomics practice. Herein, we propose deep learning as an ideal tool to
      considerably improve this prediction. A new peptide RT prediction tool, DeepRT,
      was designed using a capsule network model, and the public data sets containing
      peptides separated by reverse-phase liquid chromatography were used to evaluate
      the DeepRT performance. Compared with other prevailing RT predictors, DeepRT
      attained overall improvement in the prediction of peptide RTs with an R2 of
      ~0.994. Moreover, DeepRT was able to accommodate to the peptides that were
      separated by different types of LC, such as strong cation exchange (SCX) and
      hydrophilic interaction liquid chromatography (HILIC) and to reach the RT
      prediction with R2 values of ~0.996 for SCX and ~0.993 for HILIC, respectively.
      If a large peptide data set is available for one type of LC, DeepRT can be
      promoted to DeepRT(+) using transfer learning. Based on a large peptide data set
      gained from SWATH, DeepRT(+) further elevated the accuracy of RT prediction for
      peptides in a small data set and enabled a satisfactory prediction upon limited
      peptides approximating hundreds. Further, DeepRT automatically learns retention
      related properties of amino acids under different separation mechanisms, which
      are well consistent with retention coefficients (Rc) of the amino acids. DeepRT
      was thus proven to be an improved RT predictor with high flexibility and
      efficiency. DeepRT is available at https://github.com/horsepurve/DeepRTplus .

PMID- 30114358
TI  - Enzymatic Synthesis of the C-Glycosidic Moiety of Nogalamycin R.
AB  - Carbohydrate moieties are essential for the biological activity of anthracycline
      anticancer agents such as nogalamycin, which contains l-nogalose and l-nogalamine
      units. The former of these is attached through a canonical O-glycosidic linkage,
      but the latter is connected via an unusual dual linkage composed of C-C and O
      glycosidic bonds. In this work, we have utilized enzyme immobilization techniques
      and synthesized l-rhodosamine-thymidine diphosphate (TDP) from alpha-d-glucose-1
      TDP using seven enzymes. In a second step, we assembled the dual linkage system
      by attaching the aminosugar to an anthracycline aglycone acceptor using the
      glycosyl transferase SnogD and the alpha-ketoglutarate dependent oxygenase SnoK.
      Furthermore, our work indicates that the auxiliary P450-type protein SnogN
      facilitating glycosylation is surprisingly associated with attachment of the
      neutral sugar l-nogalose rather than the aminosugar l-nogalamine in nogalamycin
      biosynthesis.

PMID- 30114360
TI  - Improvement in Nutritional Attributes of Rice Starch with Dodecyl Gallate
      Complexation: A Molecular Dynamic Simulation and in Vitro Study.
AB  - To improve starch functionalities such as digestibility and antioxidant activity,
      rice starch was complexed with antioxidant dodecyl gallate (DG). Molecular
      dynamics simulation showed that the starch-DG inclusion complex was favorable,
      and in 50 ns, the dodecyl segment resided in the helix of the amylose cavities
      but the gallate tail left outside. This theoretical finding was validated by UV
      vis spectroscopy, calorimetric, and crystalline measurements, indicating V-type
      crystalline structures containing type I and type II inclusion complexes can be
      formed after DG complexation. Meritedly, starch digestibility was mitigated by
      synchronously increasing slowly digestible starch (5.12-22.83%) and resistant
      starch content (8.69-14.17%), and the antioxidant activity was also significantly
      increased. Such inclusion complexes thereby acted as a carrier for targeting
      delivery of DG to the human lower gastrointestinal tract with potent antioxidant
      activity. Complexation with DG synergistically improved starch digestibility and
      antioxidant activity, favoring the intervention against chronic diseases, by
      ameliorating the postprandial glycemic response and oxidative stress.

PMID- 30114361
TI  - Enhanced Wear Performance of Hybrid Epoxy-Ceramic Coatings on Magnesium
      Substrates.
AB  - Epoxy-based polymer was deposited as sealing agent on porous anodized coatings
      prepared by plasma electrolytic oxidation (PEO) to construct multilayered "soft
      hard" coatings on Mg substrates. Different thicknesses and microstructures of the
      top epoxy layer were achieved by employing different dip-coating strategies.
      Atomic force microscopy, pull-off tests, and nanoindentation tests were conducted
      to study the surface roughness, the adhesion strength of the epoxy layer, and the
      mechanical properties of each component in the hybrid coating system. The
      micropores and other defects on the anodized layers were sealed by the epoxy
      polymer, which decreased the surface roughness. The dominant abrasive wear
      behavior of blank PEO coatings was significantly reduced by the epoxy layers, and
      the wear mechanism of the hybrid coatings was proposed considering both the
      microstructure of the hybrid coatings and the mechanical properties of the
      different components in the hybrid system.

PMID- 30114362
TI  - Fabrication of Flexible Hydrogel Sheets Featuring Periodically Spaced Circular
      Holes with Continuously Adjustable Size in Real Time.
AB  - We report on the formation of stimuli-responsive structured hydrogel thin films
      whose pattern geometry can be adjusted on demand and tuned reversibly by varying
      solvent quality or by changing temperature. The hydrogel films, ~100 nm in
      thickness, were prepared by depositing layers of random copolymers comprising N
      isopropylacrylamide and ultraviolet (UV)-active methacryloyloxybenzophenone units
      onto solid substrates. A two-beam interference pattern technique was used to
      cross-link the selected areas of the film; any unreacted material was extracted
      using ethanol after UV light-assisted cross-linking. In this way, we produced
      nanoholes, perfectly ordered structures with a narrow size distribution,
      negligible tortuosity, adjustable periodicity, and a high density. The diameter
      of the circular holes ranged from a few micrometers down to several tens of
      nanometers; the hole periodicity could be adjusted readily by changing the
      optical period of the UV interference pattern. The holes were reversibly closed
      and opened by swelling/deswelling the polymer networks in the presence of ethanol
      and water, respectively, at various temperatures. The reversible regulation of
      the hole diameter can be repeated many times within a few seconds. The hydrogel
      sheet with circular holes periodically arranged may also be transferred onto
      different substrates and be employed as tunable templates for the deposition of
      desired substances.

PMID- 30114363
TI  - FeCl3-Catalyzed Regio-Divergent Carbosulfenylation of Unactivated Alkenes:
      Construction of a Medium-Sized Ring.
AB  - A FeCl3-catalyzed regio-divergent carbosulfenylation of unactivated alkenes with
      electrophilic N-sulfenophthalimides has been developed. This protocol provides a
      straightforward and efficient access to various medium-sized rings, especially
      strained 7- and 8-membered carborings with a sulfur atom attached. The endo/exo
      selectivity in the reaction depends on the atom number of the chain between arene
      and alkene. Broad substrate scope, high yields, and gram-scale synthesis
      exemplified the utility and practicability of this protocol. In addition, this
      methodology can be extended to the carboselenylation of isolated alkenes.

PMID- 30114364
TI  - Kinetic Trans-Assembly of DNA Nanostructures.
AB  - The central dogma of molecular biology is the principal framework for
      understanding how nucleic acid information is propagated and used by living
      systems to create complex biomolecules. Here, by integrating the structural and
      dynamic paradigms of DNA nanotechnology, we present a rationally designed
      synthetic platform that functions in an analogous manner to create complex DNA
      nanostructures. Starting from one type of DNA nanostructure, DNA strand
      displacement circuits were designed to interact and pass along the information
      encoded in the initial structure to mediate the self-assembly of a different type
      of structure, the final output structure depending on the type of circuit
      triggered. Using this concept of a DNA structure "trans-assembling" a different
      DNA structure through nonlocal strand displacement circuitry, four different
      schemes were implemented. Specifically, 1D ladder and 2D double-crossover (DX)
      lattices were designed to kinetically trigger DNA circuits to activate
      polymerization of either ring structures or another type of DX lattice under
      enzyme-free, isothermal conditions. In each scheme, the desired multilayer
      reaction pathway was activated, among multiple possible pathways, ultimately
      leading to the downstream self-assembly of the correct output structure.

PMID- 30114365
TI  - Measuring Ligand Binding Kinetics to Membrane Proteins Using Virion Nano
      oscillators.
AB  - Membrane proteins play vital roles in cellular signaling processes and serve as
      the most popular drug targets. A key task in studying cellular functions and
      developing drugs is to measure the binding kinetics of ligands with the membrane
      proteins. However, this has been a long-standing challenge because one must
      perform the measurement in a membrane environment to maintain the conformations
      and functions of the membrane proteins. Here, we report a new method to measure
      ligand binding kinetics to membrane proteins using self-assembled virion
      oscillators. Virions of human herpesvirus were used to display human G-protein
      coupled receptors (GPCRs) on their viral envelopes. Each virion was then attached
      to a gold-coated glass surface via a flexible polymer to form an oscillator and
      driven into oscillation with an alternating electric field. By tracking changes
      in the oscillation amplitude in real-time with subnanometer precision, the
      binding kinetics between ligands and GPCRs was measured. We anticipate that this
      new label-free detection technology can be readily applied to measure small or
      large ligand binding to any type of membrane proteins and thus contribute to the
      understanding of cellular functions and screening of drugs.

PMID- 30114366
TI  - Computational Approach to Unravel the Role of Hydrogen Bonding in the Interaction
      of NAMI-A with DNA Nucleobases and Nucleotides.
AB  - Density functional theory method in combination with a continuum solvation model
      is used to understand the role of hydrogen bonding in the interactions of
      tertiary nitrogen centers of guanine and adenine with monoaqua and diaqua NAMI-A.
      In the case of adenine, the interaction of N3 with monoaqua NAMI-A is preferred
      over that of N7 and N1 whereas, N7 site is the most preferred site over N3 and N1
      in the diaqua ruthenium-adenine interaction. In the monoaqua and diaqua NAMI-A
      guanine interactions, the N7 site is the most preferred site over the N3 site.
      Here, the strength and number of H-bonds play important roles in stabilizing
      intermediates and transition states involved in the interaction of NAMI-A and
      purine bases. Atoms in molecules and Becke surface analysis confirm that the
      interactions between monoaqua and diaqua NAMI-A with the base pairs of GC and AT
      dinucleotides leads to the structural deformation in the geometry of the base
      pairs of dinucleotides. The diaqua NAMI-A adducts induce more disruption in the
      base pairs as compared to monoaqua NAMI-A adducts. which suggests that diaqua
      NAMI-A could be a better anticancer agent than monoaqua NAMI-A. This study can be
      extended to envisage the potential applications of computational studies in the
      development of new drugs and targeted drug delivery systems.

PMID- 30114367
TI  - Exploring DrugBank in Virtual Reality Chemical Space.
AB  - The recent general availability of low-cost virtual reality headsets and
      accompanying three-dimensional (3D) engine support presents an opportunity to
      bring the concept of chemical space into virtual environments. While virtual
      reality applications represent a category of widespread tools in other fields,
      their use in the visualization and exploration of abstract data such as chemical
      spaces has been experimental. In our previous work, we established the concept of
      interactive two-dimensional (2D) maps of chemical spaces followed by interactive
      web-based 3D visualizations, culminating in the interactive web-based 3D
      visualization of extremely large chemical spaces. Virtual reality chemical spaces
      are a natural extension of these concepts. As 2D and 3D embeddings and
      projections of high-dimensional chemical fingerprint spaces have been shown to be
      valuable tools in chemical space visualization and exploration, existing
      pipelines of data mining and preparation can be extended to be used in virtual
      reality applications. Here we present an application based on the Unity engine
      and the Virtual Reality Toolkit, allowing for the interactive exploration of
      chemical space populated by DrugBank compounds in virtual reality. The source
      code of the application as well as the most recent build are available on GitHub
      ( https://github.com/reymond-group/virtual-reality-chemical-space ).

PMID- 30114368
TI  - Two-Dimensional WO3 Nanosheets Chemically Converted from Layered WS2 for High
      Performance Electrochromic Devices.
AB  - Two-dimensional (2D) transitional metal oxides (TMOs) are an attractive class of
      materials due to the combined advantages of high active surface area, enhanced
      electrochemical properties, and stability. Among the 2D TMOs, 2D tungsten oxide
      (WO3) nanosheets possess great potential in electrochemical applications,
      particularly in electrochromic (EC) devices. However, feasible production of 2D
      WO3 nanosheets is challenging due to the innate 3D crystallographic structure of
      WO3. Here we report a novel solution-phase synthesis of 2D WO3 nanosheets through
      simple oxidation from 2D tungsten disulfide (WS2) nanosheets exfoliated from bulk
      WS2 powder. The complete conversion from WS2 into WO3 was confirmed through
      crystallographic and elemental analyses, followed by validation of the 2D WO3
      nanosheets applied in the EC device. The EC device showed color modulation of
      62.57% at 700 nm wavelength, which is 3.43 times higher than the value of the
      conventional device using bulk WO3 powder, while also showing enhancement of
      ~46.62% and ~62.71% in switching response-time (coloration and bleaching). The
      mechanism of enhancement was rationalized through comparative analysis based on
      the thickness of the WO3 components. In the future, 2D WO3 nanosheets could also
      be used for other promising applications such as sensors, catalysis,
      thermoelectric, and energy conversion.

PMID- 30114369
TI  - Rational Design of Thermostable Carbonic Anhydrase Mutants Using Molecular
      Dynamics Simulations.
AB  - The stability of enzymes is critical for their application in industrial
      processes, which generally require different conditions from the natural enzyme
      environment. Both rational and random protein engineering approaches have been
      used to increase stability, with the latter requiring extensive experimental
      effort for the screening of variants. Moreover, some general rules addressing the
      molecular origin of protein thermostability have been established. Herein, we
      demonstrate the use of molecular dynamics simulations to gain molecular level
      understanding of protein thermostability and to engineer stabilizing mutations.
      Carbonic anhydrase (CA) is an enzyme with a high potential for biotechnological
      carbon capture applications, provided it can be engineered to withstand the high
      temperature process environments, inevitable in most gas treatment units. In this
      study, we used molecular dynamics simulations at 343, 353, and 363 K to study the
      relationship between structure flexibility and thermostability in bacterial alpha
      CAs and applied this knowledge to the design of mutants with increased stability.
      The most thermostable alpha-CA known, TaCA from Thermovibrio ammonificans, had
      the most rigid structure during molecular dynamics simulations, but also showed
      regions with high flexibility. The most flexible amino acids in these regions
      were identified from root mean square fluctuation (RMSF) studies, and stabilizing
      point mutations were predicted based on their capacity to improve the calculated
      free energy of unfolding. Disulfide bonds were also designed at sites with
      suitable geometries and selected based on their location at flexible sites,
      assessed by B-factor calculation. Molecular dynamics simulations allowed the
      identification of five mutants with lower RMSF of the overall structure at 400 K,
      compared to wild-type TaCA. Comparison of free-energy landscapes between wild
      type TaCA and the most promising mutants, Pro165Cys-Gln170Cys and Asn140Gly,
      showed an increased conformational stability of the mutants at 400 K.

PMID- 30114370
TI  - Efficiency of Stratification for Ensemble Docking Using Reduced Ensembles.
AB  - Molecular docking can account for receptor flexibility by combining the docking
      score over multiple rigid receptor conformations, such as snapshots from a
      molecular dynamics simulation. Here, we evaluate a number of common snapshot
      selection strategies using a quality metric from stratified sampling, the
      efficiency of stratification, which compares the variance of a selection strategy
      to simple random sampling. We also extend the metric to estimators of exponential
      averages (which involve an exponential transformation, averaging, and inverse
      transformation) and minima. For docking sets of over 500 ligands to four
      different proteins of varying flexibility, we observe that, for estimating
      ensemble averages and exponential averages, many clustering algorithms have
      similar performance trends: for a few snapshots (less than 25), medoids are the
      most efficient, while, for a larger number, optimal (the allocation that
      minimizes the variance) and proportional (to the size of each cluster) allocation
      become more efficient. Proportional allocation appears to be the most
      consistently efficient for estimating minima.

PMID- 30114371
TI  - Development of Mithramycin Analogues with Increased Selectivity toward ETS
      Transcription Factor Expressing Cancers.
AB  - Mithramycin A (1) was identified as the top potential inhibitor of the aberrant
      ETS transcription factor EWS-FLI1, which causes Ewing sarcoma. Unfortunately, 1
      has a narrow therapeutic window, compelling us to seek less toxic and more
      selective analogues. Here, we used MTMSA (2) to generate analogues via peptide
      coupling and fragment-based drug development strategies. Cytotoxicity assays in
      ETS and non-ETS dependent cell lines identified two dipeptide analogues, 60 and
      61, with 19.1- and 15.6-fold selectivity, respectively, compared to 1.5-fold for
      1. Importantly, the cytotoxicity of 60 and 61 is <100 nM in ETS cells. Molecular
      assays demonstrated the inhibitory capacity of these analogues against EWS-FLI1
      mediated transcription in Ewing sarcoma. Structural analysis shows that
      positioning the tryptophan residue in a distal position improves selectivity,
      presumably via interaction with the ETS transcription factor. Thus, these
      analogues may present new ways to target transcription factors for clinical use.

PMID- 30114372
TI  - S-Trap, an Ultrafast Sample-Preparation Approach for Shotgun Proteomics.
AB  - The success of shotgun proteomic analysis depends largely on how samples are
      prepared. Current approaches (such as those that are gel-, solution-, or filter
      based), although being extensively employed in the field, are time-consuming and
      less effective with respect to the repetitive sample processing, recovery, and
      overall yield. As an alternative, the suspension trapping (S-Trap) filter has
      been commercially available very recently in the format of a single or 96-well
      filter plate. In contrast to the conventional filter-aided sample preparation
      (FASP) approach, which utilizes a molecular weight cut-off (MWCO) membrane as the
      filter and requires hours of processing before digestion-ready proteins can be
      obtained, the S-Trap employs a three-dimensional porous material as filter media
      and traps particulate protein suspensions with the subsequent depletion of
      interfering substances and in-filter digestion. Due to the large (submicron) pore
      size, each centrifugation cycle of the S-Trap filter only takes 1 min, which
      significantly reduces the total processing time from approximately 3 h by FASP to
      less than 15 min, suggesting an ultrafast sample-preparation approach for shotgun
      proteomics. Here, we comprehensively evaluate the performance of the individual S
      Trap filter and 96-well filter plate in the context of global protein
      identification and quantitation using whole-cell lysate and clinically relevant
      sputum samples.

PMID- 30114373
TI  - Characteristics of the rhizosphere bacterial community across different
      cultivation years in saline-alkaline paddy soils of Songnen Plain of China.
AB  - The characteristics of the rhizosphere microbial community across different
      cultivation years (from 1, 3, 5, 15, 20, and 50 years) in saline-alkaline paddy
      soils in Songnen Plain of China were investigated based on sequence variation of
      16S rDNA using Illumina MiSeq sequencing. The results showed that the microbial
      community diversity varied across cultivation years, showing higher diversity in
      cultivation years >15 than in cultivation years <15. The dominant microbial
      community of the rhizosphere was mainly composed of Proteobacteria,
      Acidobacteria, Firmicutes, and Bacteroidetes. Furthermore, soil microbial
      diversity appeared to be affected directly by changes in soil properties
      corresponding to cultivated years. Diversity of Proteobacteria decreased as
      cultivated years increased; however, that of Acidobacteria showed the opposite
      direction. In addition, the soil microbial communities were clustered into two
      main groups: one from the sites cultivated for fewer than 15 years, and the other
      from the sites cultivated for more than 15 years. The abundance of nitrogen
      fixing microorganisms in the soil sample was significantly higher in soils
      cultivated for under 15 years than in those cultivated for over 15 years (P <
      0.05). Moreover, there was an obvious negative correlation between the cultivated
      years and Methanosarcina. Our findings on the dynamics of microbial community and
      its specific function in response to variable soil conditions are important for
      understanding and improving physical and chemical characteristics of saline
      alkaline soil in Songnen Plain of China.

PMID- 30114374
TI  - Migratory birds along the Mediterranean - Black Sea Flyway as carriers of
      zoonotic pathogens.
AB  - At the crossroad between Europe, Asia, and Africa, Bulgaria is part of the
      Mediterranean - Black Sea Flyway (MBSF) used by millions of migratory birds. In
      this study, bird species migrating through Bulgaria were investigated as carriers
      of zoonotic pathogens. In total, 706 birds belonging to 46 species were checked
      for the presence of various bacterial pathogens (Campylobacter, Yersinia,
      Salmonella, Listeria, Escherichia coli, Staphylococcus aureus, Francisella
      tularensis, Coxiella burnetii, Borrelia burgdorferi, and Brucella spp.). From 673
      birds we investigated fecal samples, from the remaining 33, blood samples. We
      detected Campylobacter 16S rDNA gene in 1.3% of birds, but none were of
      pathogenic Campylobacter jejuni and Campylobacter coli species. Escherichia coli
      16S rDNA gene was found in 8.8% of the birds. Out of 34 birds that transported
      Yersinia enterocolitica strains (5.05%), only 1 carried a pathogenic isolate.
      Three birds (0.4%) were carriers of nonpathogenic Salmonella strains. Four avian
      samples (0.6%) were positive for Listeria monocytogenes and 1 (0.15%) was
      positive for Brucella spp. None of the birds tested carried the tick-borne
      pathogens C. burnetii or B. burgdorferi sensu lato. Antibiotic-resistant strains
      were detected, suggesting that migratory birds could be reservoirs and spreaders
      of bacterial pathogens as well as antibiotic resistance genes.

PMID- 30114375
TI  - The Course of Lung Function in Middle-aged Heavy Smokers: Incidence and Time to
      Early Onset of Chronic Obstructive Pulmonary Disease.

PMID- 30114376
TI  - Early Plasma Matrix Metalloproteinase Profiles: A Novel Pathway in Pediatric
      Acute Respiratory Distress Syndrome.
AB  - RATIONALE: Matrix metalloproteinases (MMPs) and their endogenous tissue
      inhibitors (TIMPs) may contribute to lung injury through extracellular matrix
      degradation and modulation of inflammation and fibrosis. OBJECTIVES: To test for
      an association between MMP pathway proteins and inflammation, endothelial
      dysfunction, and clinical outcomes. METHODS: We measured MMPs in plasma collected
      on ARDS day 1 from 235 children at 5 hospitals between 2008-2017. We used latent
      class analysis to identify patients with distinct MMP profiles and then
      associated those profiles with markers of inflammation (IL-1RA, -6, -8, -10, and 
      18; MIP-1alpha and -1beta, TNF-alpha and -R2), endothelial injury (Ang-2, vWF,
      sTM), impaired oxygenation (PaO2/FiO2 ratio, oxygenation index), morbidity, and
      mortality. Measurements & Main Results: In geographically distinct derivation and
      validation cohorts, approximately one third of patients demonstrated an MMP
      profile characterized by elevated MMP-1, -2, -3, -7, -8, TIMP-1, and TIMP-2 and
      depressed active and total MMP-9. This MMP profile was associated with multiple
      markers of inflammation, endothelial injury, and impaired oxygenation on day 1 of
      ARDS, and conferred four-fold increased odds of mortality or severe morbidity
      independent of the P/F ratio and other confounders (95% CI 2.1-7.6, p<0.001).
      Logistic regression using both the P/F ratio and MMP profiles was superior to the
      P/F ratio alone in prognosticating mortality or severe morbidity (AUROC 0.75, 95%
      CI 0.68-0.82 vs. 0.66, 95% CI 0.58-0.73, p=0.009). CONCLUSIONS: Pediatric ARDS
      patients have specific plasma MMP profiles associated with inflammation,
      endothelial injury, morbidity, and mortality. MMPs may play a role in the
      pathobiology of children with ARDS.

PMID- 30114377
TI  - Genetic secrets of long-term glioblastoma survivors.
AB  - Glioblastomas account for the majority of primary brain tumors. Although
      glioblastomas are considered as rare diseases, they represent 60%-70% of all
      gliomas and in most cases have fatal consequences. Genetic analyses show great
      heterogeneity both intratumor and intertumor. This notion opens up debates about
      glioblastoma origin. Different brain cells including astrocytes, neural stem
      cells, oligodendrocyte precursor cells and glioblastoma stem cells are proposed
      as capable of initiation and reseeding a tumor; however data is still
      inconclusive. Due to high mortality rate, long term glioblastoma survivors are
      defined as patients who live longer than 2 years post diagnosis. Extreme
      survivors, living 10 years or more after diagnosis, comprise less than 1% of all
      patients. Molecular testing suggests differences in the genetic profiles of
      glioblastoma between short and long term survivors. The most informative
      indicators are IDH mutations and MGMT promotor methylation. Other genes like
      FBLN4, EMP3, IGFBP-2, IGFBP-3, LGALS3, MAOB, PDPN, SERPING1 and TIMP1 have also
      been associated with glioblastoma prolonged survival. Emerging evidence proposes
      roles of different microRNAs in predicting patient survival. Moreover, clinical
      features like seizures as a symptom at presentation, age at diagnosis, and the
      extent of the surgical resection are also factors that influence the length of
      survival. Because of the small number of long term survivors, it is difficult to
      examine these samples and draw conclusions about the genetics of glioblastoma
      longevity. To aid in the clinical care, a thorough "omics" approach is necessary
      for identifying differences between short and long term glioblastoma survivors.

PMID- 30114378
TI  - Downregulation of TSPAN13 by miR-369-3p inhibits cell proliferation in papillary
      thyroid cancer (PTC).
AB  - Previous studies demonstrated dysregulation of different microRNAs in thyroid
      cancer. Tetraspanins (TSPANs) are cell surface proteins with critical roles in
      many cellular processes, and implications in tumor development. Here we
      investigated the role of miR-369-3p in papillary thyroid cancer (PTC) and its
      association with TSPAN13. miR-369-3p and the TSPAN13 gene expression profiles of
      513 thyroid cancer and 59 normal thyroid tissues were downloaded from the Cancer
      Genome Atlas database. Thyroid cancer tissues were classified according to the
      histological type, grouped based on low and high median miR-369-3p and TSPAN13
      expression, and analyzed in relation to overall survival (OS) of patients. Human
      PTC cell lines (TPC-1 and GLAG-66) and human embryonic kidney 293T (HEK293T)
      cells were used for in vitro analysis. Transfection experiments were performed
      with synthetic miRNA mimics for miR-369-3p and small interfering RNAs for
      TSPAN13. Relative expression of miR-369-3p and TSPAN13 mRNA was determined by RT
      qPCR. Protein levels of TSPAN13 were determined by western blotting. Cell
      proliferation (CCK-8 assay), colony formation, and apoptosis (flow cytometry)
      were analyzed in transfected cells. Binding sites of miR-369-3p in TSPAN13 mRNA
      were determined by bioinformatics analysis and dual luciferase reporter assay.
      miR-369-3p was downregulated and TSPAN13 upregulated in PTC, follicular thyroid
      cancer, and tall cell variant tissues. Both low expression of miR-369-3p and high
      expression of TSPAN13 were associated with shorter OS in thyroid cancer patients.
      Overexpression of miR-369-3p significantly suppressed proliferation and promoted
      apoptosis in PTC cells. TSPAN13 was a direct target of miR-369-3p, and silencing
      of TSPAN13 phenocopied the effect of miR-369-3p mimics in PTC cells. Overall, the
      downregulation of miR-369-3p and consequent upregulation of its target TSPAN13
      appear to be involved in pathophysiology of PTC.

PMID- 30114379
TI  - Dose fall-off during the treatment of thoracic spine metastasis with CyberKnife
      stereotactic body radiation therapy (SBRT).
AB  - CyberKnife stereotactic body radiation therapy (SBRT) is becoming increasingly
      used for cancer treatment and, to maximize its clinical application, it is
      important to define the dosimetric characteristics, optimal dose and
      fractionation regimens. The aim of this study was to evaluate the dose fall-off
      in two fractionated regimens of CyberKnife SBRT during the treatment of thoracic
      spinal metastasis. Patients with spinal metastasis involving a vertebra and
      pedicle were treated with 40 Gy in 5 fractions (n = 4), and patients with spinal
      metastasis involving only a vertebra received 33 Gy in 3 fractions (n = 4). A new
      approach was used to measure absolute dose fall-off distance, relative dose fall
      off distance, and the dose fall-off per unit distance along four reference
      directions in the axial plane. Patients treated with 33 Gy/3 fractions had a
      greater absolute dose fall-off distance in direction 1 (from the point with
      maximum dose [Dmax] towards the spinal cord) and direction 3 (the opposite of the
      direction 1), a greater relative dose fall-off distance in direction 3, and a
      lower dose fall-off per unit distance in direction 1 and 3 compared to patients
      treated with 40 Gy/5 fractions (all p < 0.05). Overall, the dose fall-off towards
      the spinal cord is rapid during the treatment of thoracic spinal metastasis with
      CyberKnife SBRT, which allows a higher dose of radiation to be delivered to the
      tumor and, at the same time, better protection of the spinal cord.

PMID- 30114380
TI  - The Radial Forearm Flap: A Technique Modification for Oral Cavity Composite
      Defects Involving a Marginal Mandibulectomy.
AB  - The radial forearm flap is a versatile reconstructive option for oral cavity
      defects with highly reliable success rates. We encountered more than one flap
      compromise when we used a radial forearm flap to reconstruct the soft tissue and
      provide coverage over the mandible, after a marginal mandibulectomy. From this
      observation, we modified our technique for radial forearm harvest and inset to
      avoid placing the pedicle in compression against the mandible. The purpose of
      this article is to present the cases that led to this observation, and present
      the technique modification in design and execution that we have used.

PMID- 30114381
TI  - SEREEGA: Simulating event-related EEG activity.
AB  - BACKGROUND: Electroencephalography (EEG) is a popular method to monitor brain
      activity, but it is difficult to evaluate EEG-based analysis methods because no
      ground-truth brain activity is available for comparison. Therefore, in order to
      test and evaluate such methods, researchers often use simulated EEG data instead
      of actual EEG recordings. Simulated data can be used, among other things, to
      assess or compare signal processing and machine learning algorithms, to model EEG
      variabilities, and to design source reconstruction methods. NEW METHOD: We
      present SEREEGA, Simulating Event-Related EEG Activity. SEREEGA is a free and
      open-source MATLAB-based toolbox dedicated to the generation of simulated epochs
      of EEG data. It is modular and extensible, at initial release supporting five
      different publicly available head models and capable of simulating multiple
      different types of signals mimicking brain activity. This paper presents the
      architecture and general workflow of this toolbox, as well as a simulated data
      set demonstrating some of its functions. The toolbox is available at
      https://github.com/lrkrol/SEREEGA. RESULTS: The simulated data allows established
      analysis pipelines and classification methods to be applied and is capable of
      producing realistic results. COMPARISON WITH EXISTING METHODS: Most simulated EEG
      is coded from scratch. The few open-source methods in existence focus on specific
      applications or signal types, such as connectivity. SEREEGA unifies the majority
      of past simulation methods reported in the literature into one toolbox.
      CONCLUSION: SEREEGA is a general-purpose toolbox to simulate ground-truth EEG
      data.

PMID- 30114382
TI  - CARE-rCortex: A Matlab toolbox for the analysis of CArdio-REspiratory-related
      activity in the Cortex.
AB  - BACKGROUND: Although cardio-respiratory (CR) system is generally controlled by
      the autonomic nervous system, interactions between the cortex and these primary
      functions are receiving an increasing interest in neurosciences. NEW METHOD: In
      general, the timing of such internally paced events (e.g. heartbeats or
      respiratory cycles) may display a large variability. For the analysis of such CR
      event-related EEG potentials, a baseline must be correctly associated to each
      cycle of detected events. The open-source toolbox CARE-rCortex provides an easy
      to-use interface to detect CR events, define baselines, and analyse in time
      frequency (TF) domain the CR-based EEG potentials. RESULTS: CARE-rCortex provides
      some practical tools to detect and validate these CR events. Users can define
      baselines time-locked to a phase of respiratory or heart cycle. A statistical
      test has also been integrated to highlight significant points of the TF maps with
      respect to the baseline. We illustrate the use of CARE-rCortex with the analysis
      of two real cardio-respiratory datasets. COMPARISON WITH EXISTING METHODS:
      Compared to other open-source toolboxes, CARE-rCortex allows users to
      automatically detect CR events, to define and check baselines for each detected
      event. Different baseline normalizations can be used in the TF analysis of EEG
      epochs. CONCLUSIONS: The analysis of CR-related EEG activities could provide
      valuable information about cognitive or pathological brain states. CARE-rCortex
      runs in Matlab as a plug-in of the EEGLAB software, and it is publicly available
      at https://github.com/FannyGrosselin/CARE-rCortex.

PMID- 30114383
TI  - Convective heat transfer coefficients of open and closed Cryotop(r) systems under
      different warming conditions.
AB  - The warming of cryopreserved samples supported by small volume devices is
      governed by heat transfer phenomena which are mathematically described by the
      solution of the transient heat conduction partial differential equations; the
      convective heat transfer coefficient (h) is an important parameter involved in
      the boundary condition which is related to the fluid dynamic behavior at the
      interface device-warming fluid (water, sucrose solution or air). Unfortunately, h
      values for small volume devices (i.e. Cryotop(r)) have not been experimentally
      determined. Moreover, heat transfer coefficients during warming of Cryotop(r)
      cannot be obtained through classical dimensionless correlations expressed in
      terms of Nusselt vs. Reynolds and Prandtl numbers that are available for regular
      geometries and single materials. It is the purpose of present work to determine
      the convective heat transfer coefficients (h) by numerically solving the heat
      transfer equation applying the finite element method. Numerical simulations
      allowed to predict time-temperature histories and warming rates under different
      protocols in Cryotop(r) system which were compared with literature warming rates
      reported for this device. The h values were calculated considering the
      heterogeneous structure of the domain (microdrop, plastic-support) and the
      irregular three-dimensional geometry. The warming conditions analyzed were: a)
      open system in contact with air and sucrose solution at 23  degrees C) and b)
      closed system in contact with air and water at 23  degrees C. The h values of the
      Cryotop(r) open system immersed in sucrose solution (23  degrees C), that
      according to literature achieved a survival in the order of 80%, are in the range
      of 1800-2200 W/m2K. The h values obtained in this work for warming conditions are
      critical parameters for cryobiologists when studying heat transfer rate in this
      small volume device.

PMID- 30114384
TI  - Predominance of Leishmania major and rare occurrence of Leishmania tropica with
      haplotype variability at the center of Iran.
AB  - BACKGROUND: Leishmania major is a causative agent of zoonotic cutaneous
      leishmaniasis in the center of Iran, Abarkouh district. Molecular
      characterization and precise incrimination of Leishmania species was carried out
      to perform controlling measurements and to design treatment programs for zoonotic
      cutaneous leishmaniasis. METHODS: All smears isolated from ulcers of suspected
      patients were examined under a light microscope and graded for amastigotes
      frequency. Extraction of DNA, PCR, RFLP and sequencing of ITS-rDNA genotype were
      done to increase the efficacy of Leishmania parasites identification at their
      species-specific level and to detect any Leishmania infections within. RESULTS:
      Humans were found to be infected with L. major with high infection frequency and
      also Leishmania tropica was identified with low occurrence for the first time as
      non-native species using molecular analyses. The rates of infections was
      considerable with microscopic observation (n = 65, 73%) out of 89 smears prepared
      from suspected patients. Molecular analyses showed that the density of L. major
      was significantly higher (n = 48, 53.93%) than L. tropica (n = 4, 4.49%) (Mann
      Whitney U test: p < 0.05) and two samples (2.25%) remained ambiguous after
      several sequencing. L. major did not have diversity with two common haplotypes
      but L. tropica were found to exhibit high diversity with three novel haplotypes.
      CONCLUSION: L. major was considered the causative agent of leishmaniasis in the
      region, but the identification of a non-native L. tropica revealed the importance
      of further isolation of Leishmania parasites following molecular analyses and
      confirmation, and also revealed the importance of further isolation of Leishmania
      parasites from patients of the field areas who do not have easily access to
      health care centers for specialized treatment strategies.

PMID- 30114385
TI  - Motion estimation: A biologically inspired model.
AB  - When humans (or robots) move through a scene, the scene can be represented as an
      optic flow (optical flow) field that contains vectors representing all of the
      movement within the scene projected onto a two-dimensional sensor. A simultaneous
      sample of these resulting vectors contain a good deal of information. A general
      model of motion estimation of local vectors would therefore be valuable. This
      paper addresses the estimation of motion vectors with uniform motion over a fixed
      time period. Previous reported attempts at computing motion estimation have been
      dominated by the machine vision community; however, these attempts are not
      specifically concerned with biological plausibility. Here, the author presents a
      model of motion estimation that computes motion based on filtering the moving
      image into sinusoidal responses varying in spatial frequency and orientation
      similar to the early visual responses found in human vision. Unlike similar
      spatio-temporal energy models "motion energy" is not computed. The model is
      mathematically explicit and simulated in MATLAB. It has been tested using over
      7000 synthetic moving images with known veridical velocity (ground truth). These
      images range from sparse translating patterns containing 1 to 10,000 random
      pixels, to dense narrow band sinusoidal patterns. Simulation results show that
      the model correctly estimates motion trajectories between 84% and 100% angular
      direction error (within +/-2 degrees ), and displacement error (within +/-1
      pixel). The results remain robust at different contrasts. In addition, a number
      of psychophysical and physiological results are examined in the context of the
      model.

PMID- 30114386
TI  - Enhancement of face-sensitive ERPs in older adults induced by face recognition
      training.
AB  - A common cognitive problem reported by older people is compromised face
      recognition, which is often paralleled by age-related changes in face-sensitive
      and memory-related components in event-related brain potentials (ERPs). We
      developed a new training using photorealistic caricatures based on evidence that
      caricatures are beneficial for people with compromised face processing. Twenty
      four older participants (62-75 yrs, 13 female) completed 12 training sessions (3
      per week, 60 min each) and 24 older participants (61-76 yrs, 12 female) acted as
      controls. Before and after training (or waiting), participants took part in a
      diagnostic test battery for face processing abilities, and in ERP experiments on
      face learning and recognition. Although performance improvements during the
      training provided little evidence for generalization to other face processing
      tasks, ERPs showed substantial training-related enhancements of face-sensitive
      ERPs. Specifically, we observed marked increases of the N170, P200 and N250
      components, which may indicate training-induced enhancement of face detection and
      activation of identity-specific representations. Thus, neuronal correlates of
      face processing are plastic in older age, and can be modulated by caricature
      training.

PMID- 30114387
TI  - Salidroside alleviates ischemic brain injury in mice with ischemic stroke through
      regulating BDNK mediated PI3K/Akt pathway.
AB  - There is evidence suggesting that inhibition of apoptosis plays a critical role
      in preventing neurons from damage and even death, after brain
      ischemia/reperfusion, which shows therapeutic potential for clinical treatment of
      brain injury. In this study, We preformed MCAO model in C57BL/6J wild-type
      (BDNK+/+) and BDNK knockout (BDNF-/-) mice respectively, and investigated the
      neuroprotective effect of Salidroside (Sal) and its underlying mechanisms. The
      results showed that Sal reversed brain infarct size, reduced cerebral edema,
      decreased the neurological deficit score and diminished TUNEL positive cells
      significantly. However, BDNK deficiency inhibited the neuroprotective effect of
      Sal. In addition, Sal increased cell viability, ameliorated neuron cell injury by
      decreasing LDH activity, and inhibited cell apoptotic rate. Sal suppressed
      apoptotic signaling via DNA-binding-dependent and -independent mechanisms.
      Furthermore, the neuroprotective effect of Sal on BDNK was mediated by PI3K/Akt
      pathway, which was proved by the use of PI3K knockout (PI3K-/-) mice and siRNA
      PI3K. In summary, these data strongly suggested that Sal could be used as an
      effective neuroprotective agent to protect against ischemic stroke after cerebral
      I/R injury through regulating BDNK-mediated PI3K/Akt apoptotic pathway in DNA
      binding-dependent and -independent manners.

PMID- 30114388
TI  - Kinetic mechanism of time-dependent inhibition of CYP2D6 by 3,4
      methylenedioxymethamphetamine (MDMA): Functional heterogeneity of the enzyme and
      the reversibility of its inactivation.
AB  - We investigate the mechanism of time-dependent inhibition (TDI) of human
      cytochrome P450 2D6 (CYP2D6) by 3,4-methylenedioxymethamphetamine (MDMA,
      ecstasy), one of the most widespread recreational drugs of abuse. In an effort to
      unravel the kinetic mechanism of the formation of metabolic inhibitory complex
      (MIC) of CYP2D6 with MDMA-derived carbene we carried out a series of
      spectrophotometric studies paralleled with registration of the kinetics of time
      dependent inhibition (TDI) in CYP2D6-incorporated proteoliposomes. The high
      amplitude of spectral signal in this system allowed us to characterize the
      spectral properties of the formed MIC in details and obtain an accurate spectral
      signature of MIC formation. This information was then used in the studies with
      CYP2D6-containing microsomes of insect cells (CYP2D6 SupersomesTM). Our results
      demonstrate that in both systems the formation of the ferrous carbene-derived MIC
      is relatively slow, reversible and is not associated with the accumulation of the
      ferric carbene intermediate, as takes place in the case of CYP3A4 and
      podophylotoxin. Furthermore, the limited amplitude of MIC formation suggests that
      only a fraction (~50%) of spectrally detectable CYP2D6 in both proteoliposomes
      and Supersomes participates in the formation of MIC and is therefore involved in
      the MDMA metabolism. This observation reveals yet another example of a cytochrome
      P450 that exhibits persistent functional heterogeneity of its population in
      microsomal membranes. Our study provides a solid methodological background for
      further mechanistic studies of MIC formation in human liver microsomes and
      demonstrates that the potency and physiological relevance of MDMA-dependent TDI
      of CYP2D6 may be overestimated.

PMID- 30114389
TI  - "Pure apathy" and cognitive dysfunctions in Parkinson's disease: A meta-analytic
      study.
AB  - Parkinson's Disease (PD) is characterized by motor and non-motor symptoms such as
      cognitive deficit and behavioural disturbances. Apathy seems to be related to
      cognitive impairment, but some studies failed to confirm the relationship due to
      different methodological procedures across studies. A meta-analysis on 8 studies
      was performed to explore the cognitive correlates of apathy without depression
      and dementia (pure apathy). Global cognitive function, memory, executive
      functions, processing speed/attention/working memory, visuospatial abilities and
      language were the outcomes. The effect size of the relationship between "pure
      apathy" and reduced global cognitive functioning, executive functions, processing
      speed/attention/working memory, visuospatial functions, long-term verbal memory
      was moderate, whereas apathy was strongly associated with inhibition
      dysfunctioning. Our results revealed a strong association between "pure apathy"
      and cognitive dysfunctions, particularly deficit of memory and executive
      functions related to altered prefronto-subcortical circuitries.

PMID- 30114390
TI  - Fos-like antigen 2 (FOSL2) promotes metastasis in colon cancer.
AB  - Among different cancers, incidence and mortality of colorectal cancer (CRC) is
      one of the highest. KRAS mutation is one of the underlying features in the
      pathogenesis of CRC with CRC tumors harboring mutant KRAS exhibiting a more
      aggressive behavior compared to CRC tumors with wild type KRAS. We had earlier
      shown that the microRNA-143 (miR-143) replenishment not only chemosensitizers CRC
      cell line with mutant KRAS instead of wild-type KRAS gene, to paclitaxel-mediated
      cytotoxicity, but also inhibits cell migration and invasion ability. Hence, the
      study aimed to determine how miR-143 replenishment is inhibiting pre-metastatic
      behavior in CRC cells with mutant KRAS. Top ten mRNA targets of miR-143 as
      predicted by TargetScan were evaluated by qRT-PCR in LoVo cells which were
      performed mock transfection or miR-143 mimic transfection. Evaluation of the
      changes in cognate mRNA target(s) was done in 30 paired CRC tissue and tumor
      adjacent normal tissue specimens and in LoVo cells by western blot. Effect of the
      mRNA target on pro-metastatic behavior was assayed by gain- and loss-of-function
      studies using a combination of western blotting and in vitro cell proliferation
      and transwell migration/invasion assay in LoVo cells and in the normal colonic
      epithelium cell line FHC. In vivo effect of the cognate mRNA target on CRC
      metastasis was assayed by xenograft assay. Of the 10 predicted mRNA targets,
      FOSL2 (P < 0.05) and IGFBP5 (P > 0.05) was down regulated in LoVo cells
      transfected with the miR-143 mimic. FOSL2 mRNA levels were significantly
      downregulated in CRC tissue specimens compared with adjacent normal tissue (P <
      0.05). Immunoblot analysis showed that FOSL2, but not IGFBP5, protein expression
      is down regulated in LoVo cells after the miR-143 mimic transfection. FOSL2
      overexpression in the normal colonic epithelial cell line FHC or siRNA-mediated
      silencing in LoVo cells induced and repressed, respectively, pro-mesenchymal cell
      features. Whereas manipulation of FOSL2 expression did not have any effect on
      cell proliferation rates, silencing its expression inhibited cell migration and
      invasion ability in vitro. In addition, silencing of FOSL2 expression in the LoVo
      cells can significantly inhibited invasion of hepatic, while no effect was found
      for tumorigenic potential. Our results suggest that FOSL2 is a critical regulator
      of CRC metastasis and might be an important marker for prognostic in CRC
      patients.

PMID- 30114392
TI  - Effects of different progestins on prostaglandin biosynthesis in human
      endometrial explants.
AB  - OBJECTIVE: To compare the effects of chlormadinone acetate (CMA), dienogest (DNG)
      and drospirenone (DRSP) on prostaglandin biosynthesis in a human endometrial
      explants model. STUDY DESIGN: Human endometrial explants obtained by aspiration
      curettage and human endometrial YHES cells were stimulated with interleukin-1beta
      (IL-1beta) and exposed to CMA, DNG, DRSP or dexamethasone (DEX; YHES cells).
      Cellular messenger RNA (mRNA) levels of cyclooxygenase-2 (COX-2) were analyzed by
      reverse-transcription quantitative real-time polymerase chain reaction.
      Concentrations of prostaglandin F2alpha (PGF2alpha) in culture supernatants were
      measured by enzyme-linked immunosorbent assay. RESULTS: CMA exerted after IL
      1beta stimulation a stronger down-regulation of COX-2 mRNA compared to DNG and
      DRSP in human explants (-55% vs. -40% and 46%, respectively). The effect of CMA
      on COX-2 mRNA was significantly stronger (p=.025) than that of DNG. Moreover, the
      effect of CMA was independent from cycle phase or presence of endometriosis. In
      order to evaluate the impact of the investigated progestins on effector
      molecules, PGF2alpha release was determined in supernatants. Again, CMA reduced
      the PGF2alpha release significantly by an average of -60% (p<.01). In contrast,
      no significant reduction was found for DNG and DRSP. In YHES cells, only DEX but
      not the progestins under study exerted a significant down-regulating effect (
      79%, p<.01) on COX-2 mRNA after IL-1beta stimulation. CONCLUSION: Among the
      tested progestins, CMA displayed the most consistent suppression of prostaglandin
      biosynthesis in human endometrial explants. IMPLICATION: Among three tested
      progestins, chlormadinone acetate had the most consistent suppressive effect on
      prostaglandins in endometrial explants. These findings support clinical
      observations about the efficacy of chlormadinone acetate in dysmenorrhea
      treatment.

PMID- 30114391
TI  - Development and characterization of DNAzyme candidates demonstrating significant
      efficiency against human rhinoviruses.
AB  - BACKGROUND: Infections with human rhinoviruses (RVs) are responsible for millions
      of common cold episodes and the majority of asthma exacerbations, especially in
      childhood. No drugs specifically targeting RVs are available. OBJECTIVE: We
      sought to identify specific anti-RV molecules based on DNAzyme technology as
      candidates to a clinical study. METHODS: A total of 226 candidate DNAzymes were
      designed against 2 regions of RV RNA genome identified to be sufficiently highly
      conserved between virus strains (ie, the 5'-untranslated region and cis-acting
      replication element) by using 3 test strains: RVA1, RVA16, and RVA29. All
      DNAzymes were screened for their cleavage efficiency against in vitro-expressed
      viral RNA. Those showing any catalytic activity were subjected to bioinformatic
      analysis of their reverse complementarity to 322 published RV genomic sequences.
      Further molecular optimization was conducted for the most promising candidates.
      Cytotoxic and off-target effects were excluded in HEK293 cell-based systems.
      Antiviral efficiency was analyzed in infected human bronchial BEAS-2B cells and
      ex vivo-cultured human sinonasal tissue. RESULTS: Screening phase-generated
      DNAzymes characterized by either good catalytic activity or by high RV strain
      coverage but no single molecule represented a satisfactory combination of those 2
      features. Modifications in length of the binding domains of 2 lead candidates,
      Dua-01(-L12R9) and Dua-02(-L10R11), improved their cleavage efficiency to an
      excellent level, with no loss in eminent strain coverage (about 98%). Both
      DNAzymes showed highly favorable cytotoxic/off-target profiles. Subsequent
      testing of Dua-01-L12R9 in BEAS-2B cells and sinonasal tissue demonstrated its
      significant antiviral efficiency. CONCLUSIONS: Effective and specific management
      of RV infections with Dua-01-L12R9 might be useful in preventing asthma
      exacerbations, which should be verified by clinical trials.

PMID- 30114393
TI  - Prenatal intent and postpartum receipt of long-acting reversible contraception
      among women receiving medication-assisted treatment for opioid use disorder.
AB  - BACKGROUND: Many women with opioid use disorder (OUD) do not use highly effective
      postpartum contraception such as long-acting reversible contraception (LARC). We
      evaluated factors associated with prenatal intent and postpartum receipt of LARC
      among women receiving medication-assisted treatment (MAT) for OUD. STUDY DESIGN:
      This was a retrospective cohort study of 791 pregnant women with OUD on MAT who
      delivered at an academic institution without immediate postpartum LARC services
      between 2009 and 2012. LARC intent was defined as a documented plan for
      postpartum LARC during pregnancy and LARC receipt was defined as documentation of
      LARC placement by 8 weeks postpartum. We organized contraceptive methods into
      five categories: LARC, female sterilization, short-acting methods, barrier
      methods and no documented method. Multivariable logistic regression identified
      characteristics predictive of prenatal LARC intent and postpartum LARC receipt.
      RESULTS: Among 791 pregnant women with OUD on MAT, 275 (34.8%) intended to use
      postpartum LARC and only 237 (29.9%) attended the postpartum visit. Among 275
      women with prenatal LARC intent, 124 (45.1%) attended their postpartum visit and
      50 (18.2%) received a postpartum LARC. Prenatal contraceptive counseling (OR
      6.67; 95% CI 3.21, 13.89) was positively associated with LARC intent. Conversely,
      older age (OR 0.95; 95% CI 0.91, 0.98) and private practice provider (OR 0.48;
      95% CI 0.32, 0.72) were negatively associated with LARC intent. Although parity
      was not predictive of LARC intent, primiparous patients (CI 0.49; 95% CI 0.26,
      0.97) were less likely to receive postpartum LARC. CONCLUSIONS: Discrepancies
      exist between prenatal intent and postpartum receipt of LARC among pregnant women
      with OUD on MAT. Immediate postpartum LARC services may reduce LARC access
      barriers. IMPLICATIONS: Despite prenatal interest in using LARC, most pregnant
      women with OUD on MAT did not receive postpartum LARC. The provision of immediate
      postpartum LARC services may reduce barriers to postpartum LARC receipt such as
      poor attendance at the postpartum visit.

PMID- 30114394
TI  - Activation of TP receptors induces high release of PGI2 in coronary arteries of
      renal hypertensive rats.
AB  - AIM: To investigate the molecular mechanisms and cellular signaling pathways
      involved in the activation of TP receptors and the consequent induction of
      contractile responses in coronary arteries of renal hypertensive (2K-1C) rats.
      METHODS AND RESULTS: The coronary perfusion pressure (CPP) was lower in 2K-1C
      rats during increased coronary flow as measured by the Langendorff technique. The
      coronary contraction and relaxation were evaluated by vascular reactivity
      studies, and the molecular mechanisms were investigated on the basis of the
      protein expression of TP receptors, Cav-1, eNOS, COX-1, and COX-2, as measured by
      Western blot. The levels of eicosanoids were determined by ELISA immunoassay and
      analyzed by reverse-phase HPLC coupled to electrospray ionization mass
      spectrometry (HPLC-MS/MS). The metabolites from NO production were evaluated by
      the Griess reaction. The coronary arteries of 2K-1C rats expressed COX-2 to a
      larger extent and TP receptors to a lesser extent than the coronary arteries of
      normotensive (2K) rats. Selective COX-1 and non-selective COX inhibitors reversed
      the reduction in the contraction induced by TP receptors in the coronary arteries
      of 2K-1C rats. U46619, an agonist of TP receptors, induced a contractile response
      that was relaxed by acetylcholine (ACh). In the coronary arteries of 2K-1C rats,
      this ACh-induced relaxation depended on COX. The activation of TP receptors
      increased the production of PGI2 in the coronary arteries of 2K-1C rats. The
      results demonstrated that increased COX signaling in the coronary arteries of 2K
      1C rats mediated the low levels of CPP, the contraction induced by the activation
      of TP receptors, and the endothelium-dependent relaxation. The vasodilator PGI2
      seemed to be the major product. CONCLUSION: Activation of TP receptors increases
      production of PGI2 in coronary arteries of 2K-1C rats.

PMID- 30114395
TI  - Looking for the right mate-What we really know on the courtship and mating of
      Lucilia sericata (Meigen)?
AB  - Lucilia sericata is well known for causing myiasis in humans, livestock, pets and
      wildlife. It also vectors microbial pathogens, including paratuberculosis agents.
      This species can be exploited in maggot therapy to treat necrotic wounds,
      particularly those infected by multidrug-resistant pathogens. Despite its high
      medical and veterinary importance, our knowledge about its courtship and mating
      behavior is still limited. In this study, we quantified the courtship and mating
      behavior of L. sericata, shedding light on the potential impact of lateralization
      of selected behavioral traits during sexual interactions. When a male identified
      a female, he approached her with head pushing followed by foreleg tapping acts.
      Courtship lasted 7.65 +/- 0.4 s. During copulation attempts, the male continued
      foreleg tapping acts on the female body, and tried to achieve genital contact.
      Copula lasted 14.88 +/- 0.41 min, while male mating success was 85%. Several
      courtship and mating traits were found lateralized at population-level. Most of
      males approached the female with head pushing acts on her left side of the body.
      Both during courtship and copulation attempt phases, males mainly used the right
      foreleg to perform leg tapping acts on females. However, the impact of
      lateralized head pushing and foreleg tapping on the main behavioral parameters
      characterizing L. sericata courtship and mating was not significant, except for a
      higher number of foreleg tapping acts during copulation attempts displayed by
      right-biased males over left-biased ones. Overall, these results contribute to
      improve our basic knowledge on the reproductive behavior of L. sericata. Besides,
      selected behavioral parameters characterized here can be exploited as benchmarks
      to monitor mate quality during mass-rearing, as well as to select males with
      boosted mating competitiveness, helping to improve the success of SIT programs
      and behavior-based control tools.

PMID- 30114397
TI  - Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to
      Aggressive Prostate Cancer in Men on Active Surveillance.
AB  - PURPOSE: Age at prostate cancer (PCa) diagnosis has been positively associated
      with PCa-specific mortality, and for men on active surveillance (AS), a higher
      risk of biopsy grade reclassification (BGR) to Gleason score >=3+4 (grade group
      [GG]>=2); however, the association between age and BGR to an aggressive phenotype
      (Gleason score >=4+3 [GG>=3]) has not been explored. MATERIALS & METHODS: From
      1995-2016, 1625 men aged 41-81y with NCCN very-low (68%) or low (32%) risk PCa
      were followed on AS. We determined rates of BGR to GG>=3. Competing risk analysis
      was used to evaluate the association between age at enrollment and risk of BGR.
      Additionally, in men who underwent radical prostatectomy (RP) after BGR, we
      assessed rates of RP grade reclassification (RPGR; i.e. RP GG>biopsy GG).
      RESULTS: The 5-year incidence of BGR to GG>=3 was 4%, 7% and 14% in men <60y, 60
      69y and >=70y, respectively (p<0.001). In univariate analysis, older age was
      associated with BGR to GG>=3 (HR=2.43 per 10-year increase, p<0.001). In
      multivariable analysis adjusting for year of diagnosis, race, PSA density and
      cancer volume at diagnosis, older age remained associated with BGR to GG>=3
      (HR=2.19 per 10-year increase; p<0.001). In men who underwent RP after BGR, older
      men had higher rates of RPGR (p<0.05). CONCLUSIONS: For men on AS, older age at
      time of diagnosis was positively associated with BGR to GG>=3, and RPGR. These
      observations imply that for many older men, AS (as opposed to watchful waiting)
      remains a more appropriate management strategy.

PMID- 30114396
TI  - Do Patients With Retinal Artery Occlusion Need Urgent Neurologic Evaluation?
AB  - PURPOSE: To describe a framework for logical, immediate action to manage patients
      with retinal artery occlusion. DESIGN: Literature review and perspective.
      METHODS: Review of the literature and the author's experience. RESULTS: Since
      embolism is the most common factor causing retinal artery occlusion, to manage
      these patients, immediate evaluation and management of the source of embolism is
      critical to prevent further episodes. CONCLUSIONS: The logical, immediate action
      to manage patients with retinal artery occlusion is evaluation of the carotid
      artery and heart for embolism, fasting lipid levels and a complete blood count,
      rather than neurological evaluation, unless, of course, there are neurological
      symptoms.

PMID- 30114399
TI  - Can urine osteopontin levels, which may be correlated with nutrition intake and
      body composition, be used as a new biomarker in the diagnosis of nephrolithiasis?
AB  - BACKGROUND AND AIM: The nephrolithiasis has a multifactorial etiology resulting
      from the interaction of metabolic, genetic and environmental factors. Parameters
      such as nutrition and urinary osteopontin (OPN) level may affect kidney stone
      formation. The purpose of this study is to evaluate the correlation between
      urinary OPN level and kidney stone formation and effect of nutrition on OPN level
      in nephrolithiasis. MATERIALS AND METHODS: This study was conducted on 88
      volunteers including 44 healthy individuals and 44 patients diagnosed with
      nephrolithiasis and aging between 20 and 65 years. Some serum parameters and
      urinary OPN levels of the individuals were analyzed. Several anthropometric
      measurements of the individuals were taken and calculated their body mass index.
      Additionally, 24-hour dietary recall and water intakes were recorded and the
      participants completed food-frequency questionnaire for the evaluation of their
      nutritional status. RESULTS: Urinary OPN (ng/mL) levels of patients were lower
      than that of control group (p<0.05). Dietary energy, carbohydrate, poly
      unsaturated fatty acid (PUFA) and n-6 fatty acids intakes and urinary OPN levels
      of male patients were positively correlated (p<0.05). Additionally, there was a
      negative correlation between their urinary OPN (ng/mL) and serum creatinine
      (mg/dL) levels of female patients (p<0.05). Body weight, waist circumference, hip
      circumference and body muscle mass values of healthy males were positively
      correlated with their urinary OPN levels (p<0.05). CONCLUSIONS: Results of the
      study showed that low urinary OPN levels were correlated with increased kidney
      stone risk, and dietary habits can affect urinary OPN level.

PMID- 30114398
TI  - Binge ethanol exposure induces endoplasmic reticulum stress in the brain of adult
      mice.
AB  - Alcohol abuse causes brain damage and cognitive dysfunction. However, the
      underlying mechanisms remain elusive. Endoplasmic reticulum (ER) acts as
      machinery to ensure the proper folding of newly synthesized proteins. The
      perturbation of ER, i.e., ER stress, plays a pivotal role in some neurological
      disorders. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is
      involved in the regulation of ER stress. The current study sought to determine
      whether binge ethanol exposure induces ER stress in adult mouse brain and the
      role mTOR signaling during this process. Adult C57BL6 mice received binge ethanol
      exposure by daily gavage (5 g/kg, 25% ethanol w/v) for 1, 5 or 10 days. Binge
      ethanol exposure caused neurodegeneration and neuroinflammation after 5 days of
      exposure, and a concomitant increase of ER stress and inhibition of mTOR.
      However, ethanol exposure did not significantly alter spatial learning and
      memory, and spontaneous locomotor activity. Ethanol treatment induced ER stress
      and the death of cultured neuronal cells. Cotreatment with an ER stress
      inhibitor, sodium 4-phenylbutyrate (4-PBA) significantly diminished ethanol
      induced ER stress and neuronal apoptosis, suggesting that ER stress contributes
      to ethanol-induced neurodegeneration. Furthermore, the blockage of mTOR activity
      by rapamycin increased ER stress in cultured neuronal cells; whereas the
      activation or inhibition of ER stress by tunicamycin or 4-PBA respectively had
      little effects on mTOR signaling. These results suggested that mTOR signaling is
      upstream of ER stress and may thereby mediate ethanol-induced ER stress.

PMID- 30114400
TI  - Conserved transcriptional activity and ligand responsiveness of avian PPARs:
      Potential role in regulating lipid metabolism in mirgratory birds.
AB  - Migratory birds undergo metabolic remodeling in tissues, including increased
      lipid storage in white adipose and fatty acid uptake and oxidation in skeletal
      muscle, to optimize energy substrate availability and utilization in preparation
      for long-distance flight. Different tissues undergo gene expression changes in
      keeping with their specialized functions and driven by tissue specific
      transcriptional pathways. Peroxisome proliferator-activated receptors (PPARs) are
      lipid-activated nuclear receptors that regulate metabolic pathways involved in
      lipid and glucose utilization or storage in mammals. To examine whether PPARs
      might mediate fatty acid activation of metabolic gene programs that would be
      relevant during pre-migratory fattening, we used gray catbird as the focal
      species. PPAR isoforms cloned from catbird share high amino acid identity with
      mammalian homologs (% vs human): gcPPARalpha (88.1%), gcPPARdelta (87.3%),
      gcPPARgamma (91.2%). We tested whether gcPPARs activated fatty acid (FA)
      utilization genes using Lpl and Cpt1b gene promoter-luciferase reporters in
      mammalian cell lines. In C2C12 mouse myocytes gcPPARalpha was broadly activated
      by the saturated and unsaturated FAs tested; while gcPPARdelta showed highest
      activation by the mono-unsaturated FA, 18:1 oleic acid (+80%). In CV-1 monkey
      kidney cells gcPPARgamma responded to the poly-unsaturated fatty acid, 20:5
      eicosapentaenoic acid (+60%). Moreover, in agreement with their structural
      conservation, gcPPARs were activated by isoform selective synthetic agonists
      similar to the respective mammalian isoform. Adenoviral mediated over-expression
      of PPARalpha in C2C12 myocytes induced expression of genes involved in fatty acid
      transport, including Cd36/Fat, as well as Cpt1b, which mediates a key rate
      limiting step of mitochondrial beta-oxidation. These gene expression changes
      correlated with increased lipid droplet accumulation in C2C12 myoblasts and
      differentiated myotubes and enhanced beta-oxidation in myotubes. Collectively,
      the data predict that the PPARs play a conserved role in gray catbirds to
      regulate lipid metabolism in target tissues that undergo metabolic remodeling
      throughout the annual migratory cycle.

PMID- 30114401
TI  - Aging and the immune system: An overview.
AB  - The world is witnessing a rapid demographic shift towards an older population, a
      trend with major medical, social, economic and political implications. Aging is a
      multifaceted process, involving numerous molecular and cellular mechanisms in the
      context of different organ systems. A crucial component of aging is a set of
      functional and structural alterations in the immune system that can manifest as a
      decreased ability to fight infection, diminished response to vaccination,
      increased incidence of cancer, higher prevalence of autoimmunity and constitutive
      low-grade inflammation, among others. In addition to cell-intrinsic changes in
      both innate and adaptive immune cells, alterations in the stromal
      microenvironment in primary and secondary lymphoid organs play an important role
      in age-associated immune dysfunction. This article will provide a broad overview
      of these phenomena and point out some of their clinical and therapeutic
      implications.

PMID- 30114402
TI  - Neuroprotective effects of fatty acid amide hydrolase catabolic enzyme inhibition
      in a HIV-1 Tat model of neuroAIDS.
AB  - The HIV-1 transactivator of transcription (Tat) is a neurotoxin involved in the
      pathogenesis of HIV-1 associated neurocognitive disorders (HAND). The neurotoxic
      effects of Tat are mediated directly via AMPA/NMDA receptor activity and
      indirectly through neuroinflammatory signaling in glia. Emerging strategies in
      the development of neuroprotective agents involve the modulation of the
      endocannabinoid system. A major endocannabinoid, anandamide (N
      arachidonoylethanolamine, AEA), is metabolized by fatty acid amide hydrolase
      (FAAH). Here we demonstrate using a murine prefrontal cortex primary culture
      model that the inhibition of FAAH, using PF3845, attenuates Tat-mediated
      increases in intracellular calcium, neuronal death, and dendritic degeneration
      via cannabinoid receptors (CB1R and CB2R). Live cell imaging was used to assess
      Tat-mediated increases in [Ca2+]i, which was significantly reduced by PF3845. A
      time-lapse assay revealed that Tat potentiates cell death while PF3845 blocks
      this effect. Additionally PF3845 blocked the Tat-mediated increase in activated
      caspase-3 (apoptotic marker) positive neurons. Dendritic degeneration was
      characterized by analyzing stained dendritic processes using Imaris and Tat was
      found to significantly decrease the size of processes while PF3845 inhibited this
      effect. Incubation with CB1R and CB2R antagonists (SR141716A and AM630) revealed
      that PF3845-mediated calcium effects were dependent on CB1R, while reduced
      neuronal death and degeneration was CB2R-mediated. PF3845 application led to
      increased levels of AEA, suggesting the observed effects are likely a result of
      increased endocannabinoid signaling at CB1R/CB2R. Our findings suggest that
      modulation of the endogenous cannabinoid system through inhibition of FAAH may be
      beneficial in treatment of HAND.

PMID- 30114403
TI  - Applications of the Tunable Diode Laser Absorption Spectroscopy: In-Process
      Estimation of Primary Drying Heterogeneity and Product Temperature During
      Lyophilization.
AB  - The aim of this research was to evaluate the impact of variability in ice
      sublimation rate (dm/dt) measurement and vial heat transfer coefficient (Kv) on
      product temperature prediction during the primary drying phase of lyophilization.
      The mathematical model used for primary drying uses dm/dt and Kv as inputs to
      predict product temperature. A second-generation tunable diode laser absorption
      spectroscopy (TDLAS)-based sensor was used to measure dm/dt. In addition, a new
      approach to calculate drying heterogeneity in a batch during primary drying is
      described. The TDLAS dm/dt measurements were found to be within 5%-10% of
      gravimetric measurement for laboratory- and pilot-scale lyophilizers.
      Intersupplier variability in Kv was high for the same "type" of vials, which can
      lead to erroneous product temperature prediction if "one value" of vial heat
      transfer coefficient is used for "all vial types" from different suppliers.
      Studies conducted in both a laboratory- and a pilot-scale lyophilizer showed
      TDLAS product temperature to be within +/-1 degrees C of average thermocouple
      temperature during primary drying. Using TDLAS data and calculations to estimate
      drying heterogeneity (number of vials undergoing primary drying), good agreement
      was obtained between theoretical and experimental results, demonstrating
      usefulness of the new approach.

PMID- 30114404
TI  - Nucleophilic Addition in Aqueous Apomorphine Formulation Solutions in the
      Presence of Sodium Metabisulfite: Implications for Formulation Development and
      Manufacturing.
AB  - The purpose of this study was to investigate a potential nucleophilic addition
      mechanism in aqueous apomorphine formulation solutions in the presence of widely
      used antioxidants such as sodium metabisulfite (Na2S2O5). The findings of this
      investigation provide insights into how sodium metabisulfite can influence the
      formation of particulate under the conditions leading to the auto-oxidation of
      apomorphine to apomorphine orthoquinone. The addition products resulting from the
      reaction of bisulfite nucleophile on apomorphine orthoquinone in a Michael
      addition fashion were identified and characterized using ultraviolet-visible
      spectroscopy and mass spectrometry.

PMID- 30114405
TI  - A New Hydrate of Cyclosporine: Structural and Physicochemical Characterization.
AB  - This work highlights a new orthorhombic hydrate (Form 2) of cyclosporine (CsA), a
      widely used immunosuppressant. The uniqueness of this new form was established by
      powder X-ray diffractometry, solid-state nuclear magnetic resonance spectroscopy,
      and single crystal X-ray diffraction analysis. The crystal structure of this form
      was solved (P212121, a = 12.639 A, b = 19.758 A, c = 29.568 A, Z = 4). In
      addition, the solid-state properties of Form 2 were compared with other known
      crystalline forms of CsA by thermal analysis, water vapor sorption analysis,
      Fourier-transform infrared spectroscopy, and so on. These studies suggest that
      Form 2 is a nonstoichiometric hydrate with distinctive hydrogen bonding modes.
      More importantly, Form 2 is about an order of magnitude less soluble than the
      commercially available tetragonal form (Form 1). An interconversion map among
      various CsA solid forms was built by slurry experiments. Form 2 was the most
      stable form in aqueous systems, whereas the previously known orthorhombic hydrate
      (Form 3) was the predominant form in nonaqueous vehicles. While Form 2 as a lower
      solubility form poses greater challenge in bioavailability enhancement, the solid
      state properties of this unique hydrate may provide new drug delivery
      opportunities.

PMID- 30114406
TI  - Measurement of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma
      using automated online solid-phase extraction combined with ultra-performance
      liquid chromatography-tandem mass spectrometry and its comparison with
      coagulation assays.

PMID- 30114407
TI  - Not all chromosome aberrations can be detected by NIPT in women at advanced
      maternal age: A multicenter retrospective study.
AB  - OBJECTIVE: To discuss the detectability of NIPT for pregnant women at advanced
      maternal age (AMA), and mainly focused on how many fetal abnormalities will be
      missed by NIPT. METHODS: A total of 4194 women at AMA who accepted cytogenetic
      prenatal diagnosis were recruited in this study. All the AMA women received
      amniocentesis at 18-23 weeks. Combined with our detection level of NIPT and
      literature reports, we evaluated the detectability of NIPT. RESULTS: After cell
      karyotype analysis, a total of 233 (5.56%) fetuses were confirmed to have
      chromosomal abnormalities, including 91.0% were abnormal chromosome number and
      9.0% were abnormal chromosome structure. According to the detectability of NIPT
      we calculated, 87.6% abnormal results could also be detected by NIPT. However,
      NIPT would miss 12.4% abnormal results which could be originally found by the
      karyotype analysis of amniotic fluid cells. The major types of missed fetal
      abnormalities include structural rearrangement, mosaic and triploidy. Meanwhile,
      there were no relationship between the detectability of NIPT and the age of AMA
      pregnant women. CONCLUSIONS: About 12.4% of fetal chromosomal abnormalities will
      be missed if NIPT completely replaces invasive prenatal diagnosis in AMA women.
      Fortunately, these types of fetal abnormalities missed by NIPT did not increase
      with the age elevating of pregnant women.

PMID- 30114408
TI  - Influence of collection tubes during quantitative targeted metabolomics studies
      in human blood samples.
AB  - BACKGROUND: Plasma and serum are the most widely used matrices in clinical
      studies. However, some variability in absolute concentrations of metabolites are
      likely to be observed in these collection tubes matrices. METHODS: We analyzed
      189 metabolites using the same protocol for quantitative targeted metabolomics
      (LC-MS/MS AbsoluteIDQ p180 Kit Biocrates) in three types of samples, serum,
      plasma EDTA and citrate, of 80 subjects from the Cooperative Health Research In
      South Tyrol cohort (40 healthy elderly and 40 healthy young). RESULTS: The
      concentration levels were higher in serum than citrate and EDTA, in particular
      for amino acids and biogenic amines. The average Pearson's correlation
      coefficients were however always higher than 0.7 for these two classes of
      metabolites. We could also demonstrate that blank EDTA vacutainer tubes contain a
      significant amount of sarcosine. Finally, we compared the metabolome of young
      people against elderly subjects and found that the highest number of metabolites
      significantly changing with age was detected in serum. CONCLUSION: Serum samples
      provide higher sensitivity for biomarker discovery studies. Due to the presence
      of spurious amount of sarcosine in vacutainer EDTA tubes, plasma EDTA is not
      suitable for studies requiring accurate quantification of sarcosine.

PMID- 30114409
TI  - Silencing of PHLPP1 promotes neuronal apoptosis and inhibits functional recovery
      after spinal cord injury in mice.
AB  - AIM: Spinal cord injury (SCI) causes increased apoptosis of neurons, leading to
      irreversible dysfunction of the spinal cord. In this study, we investigated the
      effects of the progression of SCI and potential regulation of apoptosis after the
      Pleckstrin homology (PH) domain and leucine rich repeat protein phosphatase 1
      (PHLPP1) gene was silenced. MAIN METHODS: Spinal cord injection, and neuronal
      transfection with a recombinant adenovirus vector encoding small interfering RNA
      (siRNA) against PHLPP1 (AdsiPHLPP1) successfully silenced PHLPP1. These created
      in vivo and in vitro PHLPP1-silenced models, respectively, resulting in stable
      expression of the transgene in neurons. KEY FINDINGS: The results showed that
      silencing of PHLPP1 evidently reduced levels of the nuclear factor erythroid 2
      related factor 2 (Nrf2) after SCI. Western blot analysis revealed that the mice
      injected with AdsiPHLPP1 showed increased the expression of pro-apoptotic factors
      (Bax and cleaved-caspase 3), and reduced levels of neurotrophic (BDNF) and anti
      apoptotic (Bcl-2) factors, both in vivo and in vitro. The motor function of
      AdsiPHLPP1-injected mice was restored more slowly than that of wild type (WT)
      mice. In addition, the number of motor neurons surviving in the anterior horn of
      the spinal cord was also reduced after SCI. SIGNIFICANCE: Our results confirm
      that silencing of PHLPP1 promotes neuronal apoptosis and inhibits functional
      recovery after injury in vivo and in vitro. Consequently, PHLPP1 represents a
      potential therapeutic target gene for the clinical treatment of SCI.

PMID- 30114410
TI  - Analysis of heart rate variability-related indexes in the interictal period in
      patients with focal epilepsy.
AB  - AIMS: Changes in cardiac autonomic nervous function have been evaluated by
      studying the related indexes of heart rate variability (HRV) in patients with
      focal epilepsy (FE) in the interictal period. MAIN METHODS: A total of 30 FE
      patients who were treated in our department from July 2015 to May 2017, were
      included into this study. These patients were divided into three pairs of groups:
      less frequent seizure group and more frequent seizure group; medication group and
      non-medication group; <10 years disease group and >=10 years disease group. In
      addition, 16 normal healthy subjects were enrolled as the control group. The time
      domain and frequency domain indexes of HRV indexes between subgroups and the
      control group were retrospectively analyzed. KEY FINDINGS: The low-frequency/high
      frequency ratio (LF/HF) in the interictal period was higher in the more frequent
      seizure group than in the control group and less frequent seizure group (P <
      0.05). Furthermore, differences in interictal LF/HF and very low frequency (VLF)
      between the medication group and non-medication group and control group were
      statistically significant (P < 0.05). SIGNIFICANCE: In interictal period FE
      patients who present with an imbalance in autonomic nervous function, LF/HF can
      serve as an indicator to evaluate the interictal cardiac sympathetic activity of
      FE patients. Furthermore, the dynamic observation of changes in the HRV-related
      indexes of FE patients can prevent the choice of antiepileptic drugs that affect
      heart function, which is of guiding significance for evaluating autonomic nervous
      function.

PMID- 30114411
TI  - C-type natriuretic peptide (CNP) in endothelial cells attenuates hepatic fibrosis
      and inflammation in non-alcoholic steatohepatitis.
AB  - AIMS: Our previous study revealed that mice transgenic for endothelial-cell
      specific overexpression of CNP (E-CNP Tg mice) are protected against the
      increased fat weight, inflammation, and insulin resistance associated with high
      fat diet (HFD)-induced obesity. In addition, E-CNP overexpression prevented
      abnormal lipid profiles and metabolism and blocked inflammation in the livers of
      HFD-fed mice. Because obesity, dyslipidemia, and insulin resistance increase the
      risk of various liver diseases, including non-alcoholic steatohepatitis (NASH),
      we here studied the role of E-CNP overexpression in the livers of mice in which
      NASH was induced through feeding of either HFD or a choline-deficient defined l
      amino-acid diet (CDAA). MAIN METHODS: Wild-type (Wt) and E-CNP Tg mice were fed
      either a standard diet or HFD for 25 weeks or CDAA for 10 weeks. We then assessed
      hepatic and serum biochemistry; measured blood glucose during glucose tolerance
      test (GTT) and insulin tolerance test (ITT); evaluated hepatic fibrosis and
      inflammation; and performed hepatic histology and gene expression analysis. KEY
      FINDINGS: Serum triglycerides, total cholesterol, non-esterified fatty acids,
      asparagine transaminase, glucose tolerance, and insulin resistance were
      ameliorated by CNP overexpression in endothelial cells of HFD-fed E-CNP Tg mice.
      In addition, hepatic fibrosis and inflammation were decreased in HFD-fed E-CNP Tg
      mice compared with HFD-fed Wt mice. CDAA-fed E-CNP Tg mice showed improved
      glycemic control, but liver parameters, fibrosis, and inflammation were remained
      elevated and equivalent to those in CDAA-fed Wt mice. SIGNIFICANCE: The
      overexpression of CNP in endothelial cells has anti-fibrotic and anti
      inflammatory effects in liver during HFD-induced NASH in mice.

PMID- 30114413
TI  - Lipid-derived and other oxidative modifications of retinal proteins in a rat
      model of Smith-Lemli-Opitz syndrome.
AB  - Oxidative modification of proteins can perturb their structure and function,
      often compromising cellular viability. Such modifications include lipid-derived
      adducts (e.g., 4-hydroxynonenal (HNE) and carboxyethylpyrrole (CEP)) as well as
      nitrotyrosine (NTyr). We compared the retinal proteome and levels of such
      modifications in the AY9944-treated rat model of Smith-Lemli-Opitz syndrome
      (SLOS), in comparison to age-matched controls. Retinas harvested at 3 months of
      age were either subjected to proteomic analysis or to immuno-slot blot analysis,
      the latter probing blots with antibodies raised against HNE, CEP, and NTyr,
      followed by quantitative densitometry. HNE modification of retinal proteins was
      markedly (>9-fold) higher in AY9944-treated rats compared to controls, whereas
      CEP modification was only modestly (<=2-fold) greater, and NTyr modification was
      minimal and exhibited no difference as a function of AY9944 treatment. Anti-HNE
      immunoreactivity was greatest in the plexiform and ganglion cell layers, but also
      present in the RPE, choroid, and photoreceptor outer segment layer in AY9944
      treated rats; control retinas showed minimal HNE labeling. 1D-PAGE/Western blot
      analysis of rod outer segment (ROS) membranes revealed HNE modification of both
      opsin and beta-transducin. Proteomic analysis revealed the differential
      expression of several retinal proteins as a consequence of AY9944 treatment.
      Upregulated proteins included those involved in chaperone/protein folding,
      oxidative and cellular stress responses, transcriptional regulation, and energy
      production. betaA3/A1 Crystallin, which has a role in regulation of lysosomal
      acidification, was down-regulated. Hence, oxidative modification of retinal
      proteins occurs in the SLOS rat model, in addition to the previously described
      oxidation of lipids. The results are discussed in the context of the histological
      and physiological changes that occur in the retina in the SLOS rat model.

PMID- 30114412
TI  - Differential expression of corneal and limbal cytokines and chemokines throughout
      the clinical course of sulfur mustard induced ocular injury in the rabbit model.
AB  - PURPOSE: The sight threatening sulfur mustard (SM) induced ocular injury presents
      specific symptoms for each clinical stage. The acute injury develops in all of
      the exposed eyes and is characterized by erosions and severe inflammation. The
      irreversible late pathology develops only in part of the eyes, and is clinically
      expressed by chronic inflammation and corneal neovascularization (NV). The
      mechanisms underlying this injury are still in research and treatment is
      insufficient. Aiming to shed light on pathological mechanisms and improve the
      therapeutic measures, we studied the expression pattern of various cytokines and
      chemokines at different clinical stages of the ocular injury. METHODS: Rabbit
      right eye was exposed to SM vapor and a clinical follow-up was carried out up to
      4 weeks. Corneal and limbal tissues were collected at 48 h, 1w and 4w post
      exposure and IL-1alpha, IL-1beta, IL-6, TNFalpha, macrophage chemotactic protein
      (MCP)-1 and IL-8 levels were measured by commercial ELISA kits. RESULTS: SM
      exposed eyes presented an acute injury that was partially resolved within a week
      in all of the exposed eyes, and was followed by an irreversible late pathology in
      50%-80% of the eyes, beginning at 2w. A significant elevation was seen in levels
      of the studied factors, however each factor presented a unique expression
      pattern. At the peak of the acute injury, at 48 h, significantly higher levels of
      corneal IL-1alpha, IL-8, and TNFalpha and limbal IL-1alpha and MCP-1 were found
      compared to naive eyes. At 1w, corneal IL-1beta, IL-6, IL-8 and TNFalpha and
      limbal IL-8 and MCP-1 levels were significantly higher compared to naive eyes.
      During the late pathology, at 4w, elevated levels of corneal IL-1beta, IL-6 and
      MCP-1 and limbal MCP-1 and IL-8 were found only in eyes presenting NV.
      CONCLUSIONS: The levels of the studied factors changed throughout the dynamic
      course of the ocular injury. The prolonged increased levels of limbal MCP-1 and
      IL-8 may contribute to the continuous recruitment of inflammatory cells,
      characterizing the symptoms of the late pathology. The significantly elevated IL
      1beta and IL-6 at 1w, after the resolution of the acute injury but before the
      clinical manifestation of the late pathology suggests a therapeutic window for
      intervention with prevention therapy. Mapping the expression pattern of these
      cytokines and chemokines points out towards stage-specific therapeutic options.

PMID- 30114414
TI  - Prediabetes and diabetes accelerate cognitive decline and predict microvascular
      lesions: A population-based cohort study.
AB  - INTRODUCTION: The impact of prediabetes and diabetes on cognitive decline and the
      potential underlying mechanisms remain unclear. We investigated whether
      prediabetes and diabetes accelerate cognitive decline and brain aging, and the
      initial pathological changes linked to microvascular processes. METHODS: Nine
      year longitudinal data from the Swedish National Study on Aging and Care
      Kungsholmen (n = 2746, age >=60 years) and the magnetic resonance imaging
      subsample (n = 455) were used. Cognitive function was assessed with Mini-Mental
      State Examination. Brain magnetic resonance imaging markers included total brain
      tissue, white matter, gray matter, white matter hyperintensities, and hippocampal
      volumes. RESULTS: Compared with diabetes-free status, prediabetes and diabetes
      were independently associated with accelerated cognitive decline. Prediabetes was
      cross-sectionally associated with smaller total brain tissue volume (P < .01),
      particularly smaller white matter volume. Diabetes was associated with larger
      white matter hyperintensities volume. Longitudinally, diabetes was associated
      with faster white matter hyperintensities accumulation. No associations between
      prediabetes or diabetes and hippocampal volume were found. DISCUSSION: Diabetes
      and prediabetes accelerate cognitive decline and might predict microvascular
      lesions among dementia-free older adults.

PMID- 30114415
TI  - Somatic variants in autosomal dominant genes are a rare cause of sporadic
      Alzheimer's disease.
AB  - INTRODUCTION: A minority of patients with sporadic early-onset Alzheimer's
      disease (AD) exhibit de novo germ line mutations in the autosomal dominant genes
      such as APP, PSEN1, or PSEN2. We hypothesized that negatively screened patients
      may harbor somatic variants in these genes. METHODS: We applied an ultrasensitive
      approach based on single-molecule molecular inversion probes followed by deep
      next generation sequencing of 11 genes to 100 brain and 355 blood samples from
      445 sporadic patients with AD (>80% exhibited an early onset, <66 years).
      RESULTS: We identified and confirmed nine somatic variants (allele fractions:
      0.2%-10.8%): two APP, five SORL1, one NCSTN, and one MARK4 variants by
      independent amplicon-based deep sequencing. DISCUSSION: Two of the SORL1 variant
      might have contributed to the disease, the two APP variants were interpreted as
      likely benign and the other variants remained of unknown significance. Somatic
      variants in the autosomal dominant AD genes may not be a common cause of sporadic
      AD, including early onset cases.

PMID- 30114416
TI  - A Comparison between the Compass Fundus Perimeter and the Humphrey Field
      Analyzer.
AB  - PURPOSE: To evaluate relative diagnostic precision and test-retest variability of
      2 devices, the Compass (CMP, CenterVue, Padova, Italy) fundus perimeter and the
      Humphrey Field Analyzer (HFA, Zeiss, Dublin, CA), in detecting glaucomatous optic
      neuropathy (GON). DESIGN: Multicenter, cross-sectional, case-control study.
      PARTICIPANTS: We sequentially enrolled 499 patients with glaucoma and 444 normal
      subjects to analyze relative precision. A separate group of 44 patients with
      glaucoma and 54 normal subjects was analyzed to assess test-retest variability.
      METHODS: One eye of recruited subjects was tested with the index tests: HFA
      (Swedish interactive thresholding algorithm [SITA] standard strategy) and CMP
      (Zippy Estimation by Sequential Testing [ZEST] strategy), 24-2 grid. The
      reference test for GON was specialist evaluation of fundus photographs or OCT,
      independent of the visual field (VF). For both devices, linear regression was
      used to calculate the sensitivity decrease with age in the normal group to
      compute pointwise total deviation (TD) values and mean deviation (MD). We derived
      5% and 1% pointwise normative limits. The MD and the total number of TD values
      below 5% (TD 5%) or 1% (TD 1%) limits per field were used as classifiers. MAIN
      OUTCOME MEASURES: We used partial receiver operating characteristic (pROC) curves
      and partial area under the curve (pAUC) to compare the diagnostic precision of
      the devices. Pointwise mean absolute deviation and Bland-Altman plots for the
      mean sensitivity (MS) were computed to assess test-retest variability. RESULTS:
      Retinal sensitivity was generally lower with CMP, with an average mean difference
      of 1.85+/-0.06 decibels (dB) (mean +/- standard error, P < 0.001) in healthy
      subjects and 1.46+/-0.05 dB (mean +/- standard error, P < 0.001) in patients with
      glaucoma. Both devices showed similar discriminative power. The MD metric had
      marginally better discrimination with CMP (pAUC difference +/- standard error,
      0.019+/-0.009, P = 0.035). The 95% limits of agreement for the MS were reduced by
      13% in CMP compared with HFA in participants with glaucoma and by 49% in normal
      participants. Mean absolute deviation was similar, with no significant
      differences. CONCLUSIONS: Relative diagnostic precision of the 2 devices is
      equivalent. Test-retest variability of MS for CMP was better than for HFA.

PMID- 30114417
TI  - Spectral-Domain OCT Measurements in Alzheimer's Disease: A Systematic Review and
      Meta-analysis.
AB  - TOPIC: OCT is a noninvasive tool to measure specific retinal layers in the eye.
      The relationship of retinal spectral-domain (SD) OCT measurements with
      Alzheimer's disease (AD) and mild cognitive impairment (MCI) remains unclear.
      Hence, we conducted a systematic review and meta-analysis to examine the SD OCT
      measurements in AD and MCI. CLINICAL RELEVANCE: Current methods of diagnosing
      early AD are expensive and invasive. Retinal measurements of SD OCT, which are
      noninvasive, technically simple, and inexpensive, are potential biomarkers of AD.
      METHODS: We conducted a literature search in PubMed and Excerpta Medica Database
      to identify studies published before December 31, 2017, that assessed the
      associations between AD, MCI, and measurements of SD OCT: ganglion cell-inner
      plexiform layer (GC-IPL), ganglion cell complex (GCC), macular volume, and
      choroidal thickness, in addition to retinal nerve fiber layer (RNFL) and macular
      thickness. We used a random-effects model to examine these relationships. We also
      conducted meta-regression and assessed heterogeneity, publication bias, and study
      quality. RESULTS: We identified 30 eligible studies, involving 1257 AD patients,
      305 MCI patients, and 1460 controls, all of which were cross-sectional studies.
      In terms of the macular structure, AD patients showed significant differences in
      GC-IPL thickness (standardized mean difference [SMD], -0.46; 95% confidence
      interval [CI], -0.80 to -0.11; I2 = 71%), GCC thickness (SMD, -0.84; 95% CI, 
      1.10 to -0.57; I2 = 0%), macular volume (SMD, -0.58; 95% CI, -1.03 to -0.14; I2 =
      80%), and macular thickness of all inner and outer sectors (SMD range, -0.52 to 
      0.74; all P < 0.001) when compared with controls. Peripapillary RNFL thickness
      (SMD, -0.67; 95% CI, -0.95 to -0.38; I2 = 89%) and choroidal thickness (SMD
      range, -0.88 to -1.03; all P < 0.001) also were thinner in AD patients.
      CONCLUSIONS: Our results confirmed the associations between retinal measurements
      of SD OCT and AD, highlighting the potential usefulness of SD OCT measurements as
      biomarkers of AD.

PMID- 30114419
TI  - Association between Rates of Visual Field Progression and Intraocular Pressure
      Measurements Obtained by Different Tonometers.
AB  - PURPOSE: To investigate the associations between intraocular pressure (IOP)
      measurements obtained by different tonometric methods and rates of visual field
      loss in a cohort of patients with glaucoma followed over time. DESIGN:
      Prospective, observational cohort study. PARTICIPANTS: This study included 213
      eyes of 125 glaucomatous patients who were followed for an average of 2.4+/-0.6
      years. METHODS: At each visit, IOP measurements were obtained using Goldmann
      applanation tonometry (GAT), the Ocular Response Analyzer (ORA) (Reichert, Inc.,
      Depew, NY), corneal-compensated IOP (IOPcc), and the ICare Rebound Tonometer
      (RBT) (Tiolat, Oy, Helsinki, Finland). Rates of visual field loss were assessed
      by standard automated perimetry (SAP) mean deviation (MD). Linear mixed models
      were used to investigate the relationship between mean IOP by each tonometer and
      rates of visual field loss over time, while adjusting for age, race, central
      corneal thickness, and corneal hysteresis. MAIN OUTCOME MEASURES: Strength of
      associations (R2) between IOP measurements from each tonometer and rates of SAP
      MD change over time. RESULTS: Average values for mean IOP over time measured by
      GAT, ORA, and RBT were 14.4+/-3.3, 15.2+/-4.2, and 13.4+/-4.2 mmHg, respectively.
      Mean IOPcc had the strongest relationship with SAP MD loss over time (R2 = 24.5%)
      and was significantly different from the models using mean GAT IOP (R2 = 11.1%;
      95% confidence interval [CI] of the difference, 6.6-19.6) and mean RBT IOP (R2=
      5.8%; 95% CI of the difference, 11.1-25.0). CONCLUSIONS: Mean ORA IOPcc was more
      predictive of rates of visual field loss than mean IOP obtained by GAT or RBT. By
      correcting for corneal-induced artifacts, IOPcc measurements may present
      significant advantages for predicting clinically relevant outcomes in patients
      with glaucoma.

PMID- 30114420
TI  - Ovotransferrin enhances intestinal immune response in cyclophosphamide-induced
      immunosuppressed mice.
AB  - Ovotransferrin (OVT), a glycoprotein from avian egg, which has a variety of
      biological activities and immunomodulatory effects. The purpose of this research
      was to demonstrate the effect of OVT on intestinal immunomodulatory function
      which used a mouse model of cyclophosphamide (CP) induced intestinal
      immunosuppression and injury by intraperitoneal injection of 80 mg/kg. Effects of
      OVT on intestinal immunomodulatory function in CP-induced immunosuppression mice
      were detected by flow cytometry, real-time quantitative polymerase chain
      reaction, enzyme-linked immunosorbent assay, and western blot. Results showed
      that OVT effectively increased the major histocompatibility complex class II (MHC
      II) and cluster of differentiation 83 (CD83) levels to enhance intestinal
      dendritic cells (DCs) maturation and promoted the expression of cytokines and
      gene of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (IFN-gamma),
      interleukin-4 (IL-4) and interleukin-10 (IL-10). Furthermore, the imbalance ratio
      of the Th1 and Th2 in the intestine was regulated to produce an immune response
      and the expression of immunoglobulin A (IgA) and secretory immunoglobulin A
      (sIgA) were increased to promote humoral immunity by OVT-treated. Meanwhile,
      cyclophosphamide treatment induces activation of p38 MAPK, c-Jun N-terminal
      kinase (JNK) and extracellular signal-regulated kinase (ERK) to causes intestinal
      damage and blockage of p38 MAPK, JNK and ERK activation contributed to the effect
      of OVT on the repair of intestinal damage. These results indicated that OVT may
      have immunomodulatory function and could be potential functional factor to
      regulate body intestinal immunity.

PMID- 30114418
TI  - Mediterranean Diet and Incidence of Advanced Age-Related Macular Degeneration:
      The EYE-RISK Consortium.
AB  - PURPOSE: To investigate associations of adherence to the Mediterranean diet
      (MeDi) with incidence of advanced age-related macular degeneration (AMD; the
      symptomatic form of AMD) in 2 European population-based prospective cohorts.
      DESIGN: Prospective cohort study of the Rotterdam Study I (RS-I) and the
      Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (Alienor) Study
      populations. PARTICIPANTS: Four thousand four hundred forty-six participants 55
      years of age or older from the RS-I (The Netherlands) and 550 French adults 73
      years of age or older from the Alienor Study with complete ophthalmologic and
      dietary data were included in the present study. METHODS: Examinations were
      performed approximately every 5 years over a 21-year period (1990-2011) in RS-I
      and every 2 years over a 4-year period (2006-2012) in the Alienor Study.
      Adherence to the MeDi was evaluated using a 9-component score based on intake of
      vegetables, fruits, legumes, cereals, fish, meat, dairy products, alcohol, and
      the monounsaturated-to-saturated fatty acids ratio. Associations of incidence of
      AMD with MeDi were estimated using multivariate Cox proportional hazard models.
      MAIN OUTCOMES MEASURES: Incidence of advanced AMD based on retinal fundus
      photographs. RESULTS: Among the 4996 included participants, 155 demonstrated
      advanced incident AMD (117 from the RS-I and 38 from the Alienor Study). The mean
      follow-up time was 9.9 years (range, 0.6-21.7 years) in the RS-I and 4.1 years
      (range, 2.5-5.0 years) in the Alienor Study. Pooling data for both the RS-I and
      Alienor Study, participants with a high (range, 6-9) MeDi score showed a
      significantly reduced risk for incident advanced AMD compared with participants
      with a low (range, 0-3) MeDi score in the fully adjusted Cox model (hazard ratio,
      0.59; 95% confidence interval, 0.37-0.95; P = 0.04 for trend). CONCLUSIONS:
      Pooling data from the RS-I and Alienor Study, higher adherence to the MeDi was
      associated with a 41% reduced risk of incident advanced AMD. These findings
      support the role of a diet rich in healthful nutrient-rich foods such as fruits,
      vegetables, legumes, and fish in the prevention of AMD.

PMID- 30114421
TI  - Coacervates and coaggregates: Liquid-liquid and liquid-solid phase transitions by
      native and unfolded protein complexes.
AB  - Coacervates are self-assemblies formed by oppositely charged macromolecules in
      aqueous solution. Although coacervates usually take a homogeneous spherical shape
      with flowability, they have the potential to adopt unexpected macroscopic
      structures. In this study, we investigated the influence of the interaction mode
      and morphology on unfolded proteins constituting coacervates and coaggregates
      using ovalbumin (OVA) and lysozyme (LYZ) as the model systems. The unfolded
      proteins were prepared via heating at 80  degrees C and then incubated at ambient
      temperature. OVA and LYZ formed complexes at pH values between their respective
      isoelectric points in both their native and unfolded states. The unfolded
      proteins were more prone to form complexes than the native proteins due to
      hydrophobic interactions rather than electrostatic attraction. Interestingly,
      native OVA and LYZ formed liquid-like coacervates with spherical shapes, whereas
      unfolded OVA and LYZ formed solid-like coaggregates with amorphous structures.
      Understanding the difference between coacervates and coaggregates will provide
      fundamental information regarding differences between the amorphous aggregation
      and liquid-liquid phase separation of proteins.

PMID- 30114422
TI  - Proteomic approach to identify molecular signatures during experimental hepatic
      fibrosis and resveratrol supplementation.
AB  - We document the changes in sera and liver proteome during experimental hepatic
      fibrosis (HF) and its protection by resveratrol (Rsvtrl) in rats. HF was induced
      by N'-Nitrosodimethylamine (NDMA) administration thrice a week for 21-days.
      Compared to the control group, significant (P < 0.05) elevations in ALT, AST,
      ALP, gammaGT and bilirubin occurred during fibrosis. H&E, IHC for alpha-SMA and
      reticulin stainings of liver demonstrated that collagen amassing and HF were
      concurrent. Rsvtrl-supplementation refurbished hepatic architecture and lessened
      collagen deposition. 2DE proteome analyses showed ~398 (pH, 3-10) and ~129
      signatures (pH, 4-7) within 5-201 kDa range in liver and sera, respectively.
      Nearly, 45 spots in liver and 18 in sera were differentially expressed in
      fibrotic and Rsvtrl-supplemented animals. MALDI-TOF-MS/MS analysis revealed at
      least ten signatures as the potential biomarkers for HF, because of the
      significant changes (>2 fold) in their expression. Out of them, two signatures
      have not so far been characterized and we have accomplished it in this study. Our
      proteomics data provides new evidence on an overall involvement of carbohydrate,
      lipid, Ca2+ signaling and oxidative pathways during NDMA-induced HF. More
      importantly, the oxidative pathway appears to be the principal mediator in the
      NDMA-induced HF as well as the hepato-protection by Rsvtrl.

PMID- 30114423
TI  - Effect of sorbitol content on microstructure and thermal properties of chitosan
      films.
AB  - In this work, the influence of sorbitol content on the microstructure and thermal
      properties of chitosan films was investigated by Fourier transform infrared
      spectroscopy (FTIR), X-ray diffraction (XRD), Thermogravimetric analysis (TGA)
      and Differential scanning calorimetry (DSC). It showed that the addition of
      sorbitol weakened the hydrogen bonding between chitosan molecules as well as the
      electrostatic interactions existed in chitosan films. Structural analysis
      revealed that a small amount of sorbitol (~10 wt%) could facilitate the
      crystallization of chitosan, whereas it was seriously hindered at high content of
      sorbitol (~50 wt%). The thermal behavior of composite films indicated that the
      sorbitol addition did not reduce the thermal stability of polymer films. When the
      sorbitol content rose to above 30 wt%, phase separation may occur and two glass
      transitions presented in composite films. The lower temperature transition was
      associated with the glass-rubber transition of sorbitol-rich phase, and the
      higher one was related to chitosan-rich phase. These results implied that the
      microstructure as well as properties of the plasticized chitosan films can be
      controlled by adding sorbitol, which is important for their usage as packaging
      materials.

PMID- 30114424
TI  - Immobilization of alpha-amylase on chitosan-montmorillonite nanocomposite beads.
AB  - Enzyme immobilization is a way to increase efficiency of the enzyme and
      facilitate its recovery. The aim of this study was to immobilize alpha-amylase on
      chitosan-montmorillonite nanocomposite beads. Nanocomposite beads were prepared
      as the carrier for the enzyme stabilization and their surface was modified by
      Glutaraldehyde. Alpha-amylase was immobilized on nanocomposite beads by covalent
      bonding. The results of scanning electron microscopy (SEM) showed that particle
      size range of montmorillonite was 10-30 nm. This study indicated that the enzyme
      immobilization efficiency was 87%. The activity of free and immobilized enzyme
      during 40 days of storage at 4  degrees C decreased 95% and 36%, respectively.
      The results showed that the immobilized enzyme activity after reusing five times
      decreased about 47%. This study indicated that the immobilized enzyme activity
      was higher than the free enzyme at different temperatures. Also the immobilized
      enzyme was more stable than the free enzyme at lower pH. The results of kinetic
      parameters showed that Km values of the immobilized enzyme (9.12 MUmol/ml) were
      higher than free enzyme (6.80 MUmol/ml). The Vmax values for the free and
      immobilized enzyme were 1.30 and 0.629 MUmol/mg.min, respectively.

PMID- 30114425
TI  - Structural characterization and anti-A549 lung cancer cells bioactivity of a
      polysaccharide from Houttuynia cordata.
AB  - A water-soluble pectic polysaccharide HCA4S1 was isolated from Houttuynia cordata
      and purified by DEAE Cellulose and Sephacryl S-300 column. HCA4S1 with an average
      molecular weight of 21.7 kDa mainly consisted of rhamnose, galacturonic acid,
      galactose, and arabinose. By using partial acid hydrolysis, methylation analysis,
      and NMR spectra, the structure of this polysaccharide is found to have a backbone
      consisting of 1,4-linked alpha-d-GalA and 1,2,4-linked alpha-l-Rha. The latter
      was substituted at C-4 position by 1,4 linked, 1,6-linked beta-Galp, or Teminal
      linked beta-Gal. Bioactivity test showed that this polysaccharide might inhibit
      the proliferation of A549 lung cancer cell by inducing cell cycle arrest and
      apoptosis. The expression of cleaved caspase 3 and cyclinB1 was observed to be
      upregulated after the treatment with this polysaccharide. Collectively, these
      results suggest that the pectin HCA4S1 from Houttuynia cordata is of potential
      value in the treatment of lung cancer, though the underlying mechanisms remain to
      be further confirmed.

PMID- 30114426
TI  - Preparation, structural characterization and bioactivities of Se-containing
      polysaccharide: A review.
AB  - Se-containing polysaccharide is known to Se-conjugated macromolecule, with potent
      bioactivities due to the synergistic effects of Se and native polysaccharide. It
      is not only explored as a novel Se source in dietary supplement, but also as the
      superb bioactive component owning various functions, including antioxidant,
      antitumor, immune-enhancement, hepatoprotective, antidiabetic, anti-inflammatory
      and neuroprotective activities. Se-containing polysaccharide can exert the
      efficacy of Se and polysaccharide, and its activities are much higher than those
      of Se or polysaccharide. In the last decades, numerous reports on Se-containing
      polysaccharide (including natural Se-containing polysaccharide and selenylated
      polysaccharide) appeared in literature. For the first time, this article
      systematically introduces recent advances on preparation, structural
      characterization and bioactivities of Se-containing polysaccharide in details,
      and discusses its future prospects and the weaknesses in the current study.

PMID- 30114427
TI  - Influence of debranching and retrogradation time on behavior changes of
      Amorphophallus paeoniifolius nanostarch.
AB  - In this study, Amorphophallus paeoniifolius (elephant foot yam) starch
      nanoparticles (SNPs) were produced using a native facile and green procedure
      integrated with debranching and recrystallization. SNPs were produced through
      debranching with pullulanase followed by 12- and 24-h retrogradation time.
      Transmission electron microscopy, dynamic light scattering, infrared
      spectroscopy, differential scanning colorimetry, and X-ray diffraction were
      utilized to illustrate the morphology, molecular structure, in vitro
      digestibility, and behavior changes of SNPs. The results revealed that
      debranching and the retrogradation time influenced the yield of SNPs. The results
      showed that the particle size of the nanoparticles ranged between 182.07 and
      198.1 nm. Prolonging the retrogradation time from 12 to 24-h led to an increase
      in gelatinization temperatures and enthalpy of SNPs. In contrast with the
      traditional method for preparing SNPs, the method developed in the present study
      has the advantages of increased yield and rapidity, and also useful for
      developing new materials in biomedical applications.

PMID- 30114428
TI  - Effect of xanthan gum or pectin addition on Sacha Inchi oil-in-water emulsions
      stabilized by ovalbumin or tween 80: Droplet size distribution, rheological
      behavior and stability.
AB  - The aim of this work was to studied the formation, stability and characterization
      of oil-in-water emulsions formed by Sacha Inchi oil (SIO) 8% (w/w) with either
      ovalbumin (Ova) or Tween 80 (Tw80), as emulsifiers at 0.5%-2.0% (w/w) and
      stabilized with pectin (Pec) at 1.0%-3.0% (w/w) or xanthan gum (XG) at 0.25%-1.0%
      (w/w). The emulsions were evaluated at 0, 1, 7 and 14 days after preparation and
      kept at a temperature of 25 +/- 1  degrees C for the zeta-potential, particle
      size distribution, polydispersion, and emulsion stability index measurements. The
      emulsions were characterized by optical microscopy, viscosity and rheological
      behavior. It was observed that it is possible to form oil-in-water emulsions with
      SIO-Ova and Pec that are stable at 25  degrees C for at least 14 days with a
      polydispersion value between 0.2 and 0.5. However, the emulsions with SIO-Ova and
      XG are stable at several concentrations of XG but are more viscous and can form
      aggregates. The presence of a biopolymer is essential for the kinetic stability
      of the emulsions containing Ova as the emulsifier. For the emulsions containing
      Tw80, this conclusion applies only to emulsions with XG concentrations of 0.5% to
      1.0%, in which the stability mechanism is distinct.

PMID- 30114429
TI  - Postnatal stress is associated with impaired fear conditioning and extinction,
      and heightened hippocampal fibroblast growth factor 2, in mother rats.
AB  - Rats exposed to early-life maternal separation (MS) exhibit later alterations in
      fear conditioning and impairments in fear extinction. As MS creates long-lasting
      anxiety in the mother, the present study assessed the influence of MS on fear
      conditioning and extinction in mother rats. It also examined whether estrous
      cycle effects on extinction, which are robust in nulliparous rats, but abolished
      in primiparous rats, re-emerge after MS. Following parturition, pups were removed
      from their mothers for 3 h daily from postpartum day 2-14 (MS), or remained
      housed with their mothers (standard reared condition, SR). Pups were weaned at
      postpartum day 24, and three months later, mothers received fear conditioning,
      extinction training, and test for extinction recall over three days. Extinction
      training took place during Proestrus (high estradiol and progesterone) or
      Metestrus (low estradiol and progesterone). Similar to past findings in non
      stressed mothers, estrous cycle was not associated with conditioned fear
      expression (indexed by fear responses at the start of extinction training) or
      extinction recall in either MS or SR mothers. However, MS mothers exhibited
      weaker conditioned fear expression and impaired extinction recall, relative to SR
      mothers. Hippocampal fibroblast growth factor-2, a neurotrophin involved in
      stress regulation and fear expression, was elevated in MS relative to SR mothers.
      These results indicate that postnatal stress has long-lasting consequences for
      neural and behavioral systems involved in fear learning and inhibition without
      altering the involvement of ovarian hormones in these processes.

PMID- 30114430
TI  - The absence of maternal pineal melatonin rhythm during pregnancy and lactation
      impairs offspring physical growth, neurodevelopment, and behavior.
AB  - Maternal melatonin provides photoperiodic information to the fetus and thus
      influences the regulation and timing of the offspring's internal rhythms and
      preparation for extra-uterine development. There is clinical evidence that
      melatonin deprivation of both mother and fetus during pregnancy, and of the
      neonate during lactation, results in negative long-term health outcomes. As a
      consequence, we hypothesized that the absence of maternal pineal melatonin might
      determine abnormal brain programming in the offspring, which would lead to long
      lasting implications for behavior and brain function. To test our hypothesis, we
      investigated in rats the effects of maternal melatonin deprivation during
      gestation and lactation (MMD) to the offspring and the effects of its therapeutic
      replacement. The parameters evaluated were: (1) somatic, physical growth and
      neurobehavioral development of pups of both sexes; (2) hippocampal-dependent
      spatial learning and memory of the male offspring; (3) adult hippocampal
      neurogenesis of the male offspring. Our findings show that MMD significantly
      delayed male offspring's onset of fur development, pinna detachment, eyes
      opening, eruption of superior incisor teeth, testis descent and the time of
      maturation of palmar grasp, righting reflex, free-fall righting and walking.
      Conversely, female offspring neurodevelopment was not affected. Later on, male
      offspring show that MMD was able to disrupt both spatial reference and working
      memory in the Morris Water Maze paradigm and these deficits correlate with
      changes in the number of proliferative cells in the hippocampus. Importantly, all
      the observed impairments were reversed by maternal melatonin replacement therapy.
      In summary, we demonstrate that MMD delays the appearance of physical features,
      neurodevelopment and cognition in the male offspring, and points to putative
      public health implications for night shift working mothers.

PMID- 30114431
TI  - LH and fertility: A discussion of identifying the period of maximal fertility in
      naturally cycling women.

PMID- 30114432
TI  - Gamma radiation-induced in vitro hormetic apogamy in the fern Pityrogramma
      calomelanos (L.) link.
AB  - Pityrogramma calomelanos (L.) Link, popularly known as "Silver fern" has
      significant importance as a medicinal plant used traditionally for its
      astringent, analgesic, anti-haemorrhagic, anti-hypertensive, anti-pyretic and
      anthelminthic properties. This fern demonstrates an increased morphogenetic
      potential towards sporophyte formation, upon exposure to low doses of gamma
      radiation. Young sporophytic leaf crosier cultures were established in vitro on
      agar based Knop's media with and without 20 g/l sucrose. The cultures were
      subjected to 60Co radiations in the range of 2.5-100 Gy. Apospory (production of
      gametophytes on sporophytic tissue without spores) was observed on leaf tissue
      cultured on Knops media with and without sucrose in P. calomelanos, at the end of
      60 days. 5 Gy treated explants showed high number of aposporous gametophytes and
      was comparable to the control. Other tested doses reduced the aposporous
      gametophyte production significantly. In the second phase of the experimentation,
      the cultures were retained on the gametophyte induction media for a period of 4
      weeks. Aposporous gametophytes were observed to proliferate with occasional
      development of antheridia. At the end of 4 weeks, morphogenetic development on
      the gametophytic tissue resulted in a significantly higher number of apogamous
      sporophytes (production of sporophytes without fusion of gametes) were obtained
      on 5 Gy treated tissue as compared to control and all the other treated explants.
      Apogamous sporophytes thus produced were successfully grown in the greenhouse and
      transferred to the field. Thus the use of gamma radiation in vitro not only
      reduced the need for sucrose for induction of apospory in P.calomelanos, it also
      exhibited hormesis at 5 Gy for improved sporophyte production.

PMID- 30114433
TI  - Development of a TaqMan-based real-time PCR for detecting duck adenovirus 3.
AB  - Recently, a novel duck adenovirus (designated as duck adenovirus 3, DAdV-3) was
      discovered in Muscovy ducks, China. Here, we developed a TaqMan-based real-time
      PCR assay (qPCR) for the detection of DAdV-3 infection. After the optimization of
      the qPCR conditions, the lower limit of detection for DAdV-3 infection was 40.9
      copies/MUl. No cross-reactivity was observed with other duck-derived pathogens.
      Intra- and inter-assay variability was less than 2.30%. DAdV-3 was detected in
      embryos and newly hatched ducklings by qPCR assay, the findings provided evidence
      of possible vertical transmission of DAdV-3. The developed qPCR analysis showed
      high specificity, sensitivity, and reproducibility, thereby indicating that it
      can be used in future investigations on the pathogenesis and epidemiology of DAdV
      3.

PMID- 30114434
TI  - Reversal of morphine conditioned behavior by an anti-dopaminergic post-trial drug
      treatment during re-consolidation.
AB  - Morphine has potent pro-dopamine effects that can be manifested as hyper
      locomotion and these behavioral effects can undergo conditioning and
      sensitization. The aim of the present study was to assess whether an inhibitory
      dopaminergic post-trial treatment (0.05 mg/kg apomorphine) given during re
      consolidation could reduce morphine conditioning. To induce conditioned morphine
      hyperactivity and control for morphine exposure, a paired/unpaired Pavlovian
      conditioning protocol was used. The morphine paired groups received morphine in
      the open-field test arena and the unpaired groups received the same morphine (10
      mg/kg) treatments but in a different environment. The morphine treatments were
      administered once per day for 5 days. With repeated treatments, the paired
      morphine groups developed a sensitized hyper-locomotion response whereas the
      unpaired morphine groups did not differ from vehicle groups. Subsequently, the
      paired, unpaired and vehicle groups were given four daily non-drug 5 min
      conditioning tests. In these conditioning tests, the paired but not the unpaired
      and vehicle groups exhibited a conditioned locomotor stimulant response. These
      groups were subdivided into matched groups and received either vehicle or 0.05
      mg/kg apomorphine either during re-consolidation immediately post-test or after
      re-consolidation 15 min post-test. In the immediate post-trial treatment groups,
      the morphine conditioned response in the paired group was eliminated after only
      one post-trial apomorphine treatment. The same immediate 0.05 mg/kg apomorphine
      post-trial treatments had no effect on the unpaired morphine or vehicle groups.
      In the paired group that received vehicle immediately post-trial, the conditioned
      response remained robust and unchanged over the four conditioning tests. In the
      post-trial 15 min delay treatment groups, the post-trial apomorphine treatments
      had no effect on the morphine conditioned response. These results showed that the
      inhibition of dopamine activity by apomorphine during the re-consolidation of a
      cue activated morphine conditioned response eliminated morphine conditioned
      effects. In that morphine conditioned effects are important for the initiation of
      addiction and in triggering drug craving and relapse, this finding has potential
      relevance to opioid addiction treatment.

PMID- 30114435
TI  - Spleen tyrosine kinase from Nile tilapia (Oreochromis niloticus): Molecular
      characterization, expression pattern upon bacterial infection and the potential
      role in BCR signaling and inflammatory response.
AB  - Spleen tyrosine kinase (SYK), a member of non-receptor tyrosine kinase family,
      plays an important role in immune responses against pathogen infection, which is
      capable of activating B cells signaling pathway and regulating inflammatory
      response. In this study, Nile tilapia (Oreochromis niloticus) ortholog (OnSYK)
      was identified and characterized at expression pattern against bacterial
      infection, function in B cells activation pathway and inflammatory response. The
      cDNA of OnSYK ORF contained 1851 bp of nucleotide sequence encoding polypeptides
      of 616 amino acids. The deduced OnSYK protein was highly homologous to other
      species SYK, containing two SH2 domains and a TyrKc domain. Spatial mRNA
      expression analysis revealed that OnSYK had wide tissue distribution and was
      highly expressed in the liver. After challenge of Streptococcus agalactiae (S.
      agalactiae) in vivo, mRNA expression of OnSYK was significantly up-regulated in
      the head kidney, spleen and liver. The up-regulation of OnSYK transcript was also
      displayed in the head kidney and spleen leukocytes stimulation with S. agalactiae
      and LPS in vitro, which was confirmed at protein level in the head kidney
      leukocytes by FACS analysis. In addition, after induction with mouse anti-OnIgM
      monoclonal antibody in vitro, the expressions of OnSYK and its downstream
      molecules (OnLYN, OnBLNK and OnAP-1) were significantly up-regulated in the head
      kidney leukocytes, and pharmacological inhibition of SYK activity with inhibitor
      (P505-15) significantly attenuated the expressions of OnLYN, OnBLNK and OnAP-1.
      Moreover, upon LPS challenge, the expressions of OnSYK, OnTNF-alpha, OnIL-6 and
      OnAP-1 were also up-regulated in the head kidney monocytes/macrophages. After
      treatment with SYK inhibitor (BAY 61-3606), the expressions of OnTNF-alpha, OnIL
      6 and OnAP-1 were inhibited in the LPS-challenged head kidney
      monocytes/macrophages. Taken together, the results of this study indicated that
      OnSYK, playing potential roles in BCR signaling and inflammatory response, was
      likely to get involved in host defense against bacterial infection in Nile
      tilapia.

PMID- 30114436
TI  - Epigenetic aberrations of miR-369-5p and DNMT3A control Patched1 signal pathway
      in cardiac fibrosis.
AB  - Modulation of epigenetic marks has promised efficacy for treating fibrosis.
      Cardiac fibroblast is the primary source of activated myofibroblasts that produce
      extracellular matrix (ECM) in cardiac fibrosis, but the mechanisms underlying
      this process are incompletely understood. Here we show that microRNA-369-5p (miR
      369-5p) through DNMT3A hypermethylation and suppression of the Patched1 pathway
      leads to fibroblast proliferation in cardiac fibrosis. Forty adult male Sprague
      Dawley (SD) rats were randomly divided into two groups (sham and AAC group),
      cardiac fibrosis was produced by abdominal aortic constriction, and the operation
      of abdominal aortic constriction was carried out according to the method
      described. Cardiac fibroblasts (CFs) were harvested from SD neonate rats and
      cultured. Importantly, miR-369-5p bind directly to DNMT3A with high affinity. MiR
      369-5p leads to inhibition of DNMT3A enzyme activity. Exogenous miR-369-5p in
      cells induces aberrant DNA methylation of the Patched1, resulting in
      hypermethylation of low to moderately methylated regions. Moreover,
      Overexpression of miR-369-5p in cardiac fibroblast cells inhibits proliferation.
      We identify DNMT3A as miR-369-5p target genes and demonstrate that inhibition of
      miR-369-5p expression augments cell proliferation by activating DNMT3A and
      suppression of the Patched1 pathway. Together, our results highlight miR-369-5p
      mediated DNMT3A epigenetic silencing of Patched1 as a mechanism of fibroblast
      proliferation in cardiac fibrosis.

PMID- 30114437
TI  - Stimulus complexity matters when you hear your own voice: Attention effects on
      self-generated voice processing.
AB  - The ability to discriminate self- and non-self voice cues is a fundamental aspect
      of self-awareness and subserves self-monitoring during verbal communication.
      Nonetheless, the neurofunctional underpinnings of self-voice perception and
      recognition are still poorly understood. Moreover, how attention and stimulus
      complexity influence the processing and recognition of one's own voice remains to
      be clarified. Using an oddball task, the current study investigated how self
      relevance and stimulus type interact during selective attention to voices, and
      how they affect the representation of regularity during voice perception. Event
      related potentials (ERPs) were recorded from 18 right-handed males. Pre-recorded
      self-generated (SGV) and non-self (NSV) voices, consisting of a nonverbal
      vocalization (vocalization condition) or disyllabic word (word condition), were
      presented as either standard or target stimuli in different experimental blocks.
      The results showed increased N2 amplitude to SGV relative to NSV stimuli.
      Stimulus type modulated later processing stages only: P3 amplitude was increased
      for SGV relative to NSV words, whereas no differences between SGV and NSV were
      observed in the case of vocalizations. Moreover, SGV standards elicited reduced
      N1 and P2 amplitude relative to NSV standards. These findings revealed that the
      self-voice grabs more attention when listeners are exposed to words but not
      vocalizations. Further, they indicate that detection of regularity in an auditory
      stream is facilitated for one's own voice at early processing stages. Together,
      they demonstrate that self-relevance affects attention to voices differently as a
      function of stimulus type.

PMID- 30114438
TI  - ETS-1 induces Sorafenib-resistance in hepatocellular carcinoma cells via
      regulating transcription factor activity of PXR.
AB  - Transcription factor E26 transformation specific sequence 1 (ETS-1) is a primary
      regulator in the metastasis of human cancer cells, especially hepatocellular
      carcinoma (HCC) cells; and it would affect the prognosis of HCC patients who
      received chemotherapies. However, the regulatory role of ETS-1 in the resistance
      of HCC cells to molecular-targeting agent remains poorly understood. In the
      present work, we demonstrate that high ETS-1 expression correlates with poor
      prognosis of advanced HCC patients received Sorafenib treatment. Mechanistically,
      ETS-1 binds to nuclear Pregnane X receptor (PXR) directly and enhances PXR's
      transcription factor activity, which further leads to the induction of the PXR's
      downstream multi-drug resistance related genes. Overexpression of ETS-1
      accelerates the metabolic clearance of Sorafenib in HCC cells and leads to the
      better survival and faster migration of those cells. The therapeutic studies show
      that ETS-1 promotes the Sorafenib-resistance of HCC tumor models and ETS-1
      blockade enhances the anti-tumor capacity of Sorafenib by decreasing PXR
      activation. Thus, our study suggests that ETS-1 could enhance the activation of
      PXR and be a potential therapeutic target for overcoming Sorafenib resistance in
      HCC treatment.

PMID- 30114439
TI  - Spectrum of Type I and Type II syndromes and associated malformations in Chinese
      patients with Mayer-Rokitansky-Kuster-Hauser syndrome: A retrospective analysis
      of 274 cases.
AB  - OBJECTIVE: To analyze the spectrum of Type I and Type II malformations in Chinese
      patients with Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. METHODS: It was a
      cross-sectional descriptive study that used data from a National Clinical
      Research Center for Obstetrical and Gynecological Diseases of China, reviewed
      from January 2009 to July 2017. Patients with MRKH syndrome, both in- and out
      patients were reviewed and analyzed. RESULTS: A total of 274 cases were included
      in the analysis: 197 (71.9%) with Type I MRKH syndrome and the remaining 77
      (28.1%) with Type II MRKH syndrome. The rate of concurrent deformities was 13.1%
      (32/244) for renal malformation, and 39.2% (49/125) for skeletal malformation.
      Nine patients had both renal and skeletal malformations (MURCS). Cardiac,
      neurologic and other malformations (e.g., anal atresia) were sporadic. The
      percentage of Type II MRKH syndrome in our cohort was considerably higher than
      that reported (7.2%) in a previous large-scale study in southern China, but lower
      than that (46.2%) reported for Caucasians. CONCLUSIONS: The spectrum of Type I
      and Type II MRKH syndrome varies across different races and geological locations.

PMID- 30114440
TI  - The role of T cells in the pathogenesis of Parkinson's disease.
AB  - Recent evidence has shown that neuroinflammation plays a key role in the
      pathogenesis of Parkinson's disease (PD). However, different components of the
      brain's immune system may exert diverse effects on neuroinflammatory events in
      PD. The adaptive immune response, especially the T cell response, can trigger
      type 1 pro-inflammatory activities and suppress type 2 anti-inflammatory
      activities, eventually resulting in deregulated neuroinflammation and subsequent
      dopaminergic neurodegeneration. Additionally, studies have increasingly shown
      that therapies targeting T cells can alleviate neurodegeneration and motor
      behavior impairment in animal models of PD. Therefore, we conclude that abnormal
      T cell-mediated immunity is a fundamental pathological process that may be a
      promising translational therapeutic target for Parkinson's disease.

PMID- 30114441
TI  - In vitro activity of lascufloxacin, a novel fluoroquinolone antibacterial agent,
      against various clinical isolates of anaerobes and Streptococcus anginosus group.
AB  - The in vitro activities of lascufloxacin were evaluated by comparison with seven
      reference compounds using 412 clinical isolates of anaerobes and Streptococcus
      anginosus group. Lascufloxacin showed potent and broad antibacterial activities
      greater than those of existing quinolones against the clinical isolates used in
      this study.

PMID- 30114442
TI  - Clinical epidemiology of Clostridium difficile infection among hospitalized
      patients with antibiotic-associated diarrhea in a university hospital of Brazil.
AB  - A cohort of 110 adult individuals was analyzed to compare clinical
      characteristics of hospitalized patients who received antibiotics and developed
      Clostridium difficile infection (CDI) with those who received antibiotics and did
      not develop the disease in a university Hospital in Brazil. CDI was diagnosed by
      toxigenic culture and C. difficile isolates were characterized by PCR ribotyping.
      Stool samples were also screened for Clostridium perfringens, methicillin
      resistant Staphylococcus aureus (MRSA) and Klebsiella oxytoca. The prevalence of
      CDI among patients with AAD was 31.8%. C. difficile diarrhea was significantly
      associated with the severity of underlying comorbidities at admission (OR = 1.21;
      95% CI, 1.04-1.40) and with the number of antibiotics used during hospitalization
      (OR = 1.43; 95% CI, 1.07-1.92). Diabetes mellitus was markedly associated with a
      higher risk of death in patients with AAD (OR = 6.38; 95% CI, 1.33-30.7). PCR
      ribotypes 014/020 and 106 (20.6% each) were the most common among the isolates.
      Binary toxin-encoding gene (cdtB) was detected in six samples, but previously
      described hypervirulent ribotypes 027 and 078 were not found. K. oxytoca and
      enterotoxigenic C. perfringens were not detected, while only one patient (0.9%)
      was positive for MRSA. Our results indicate that comorbidity severity and the
      number of antibiotics used during hospitalization are strong independent
      predictors of nosocomial C. difficile diarrhea. Diabetes was associated with a
      higher mortality among patients with AAD. A huge diversity of C. difficile
      ribotypes was observed in our study, although classical hypervirulent strains
      were not observed.

PMID- 30114443
TI  - Caries-arresting effects of silver diamine fluoride and sodium fluoride on
      dentine caries lesions.
AB  - OBJECTIVES: To investigate the remineralising effect and bacterial growth
      inhibition of 38% silver diamine fluoride (SDF) solution and 5% sodium fluoride
      (NaF) varnish on artificial dentine caries lesions. METHODS: Demineralised
      dentine blocks were treated with SDF + NaF (Group 1), SDF (Group 2), NaF (Group
      3) and water (Group 4) and subjected to a Streptococcus mutans biofilm challenge.
      Lesion depth, precipitates' characteristics and matrix (collagen)-to-mineral
      ratio were evaluated by micro-computer tomography (micro-CT), X-ray diffraction
      (XRD) and Fourier transform infrared spectroscopy (FTIR), respectively. The
      biofilm kinetics, viability and topography were assessed by counts of colony
      forming units (CFUs), confocal laser scanning microscopy (CLSM) and scanning
      electron microscopy (SEM), respectively. Data were analysed by two-way ANOVA
      test. RESULTS: The lesion depths of Groups 1-4 were 170 +/- 28 MUm, 160 +/- 32
      MUm, 353 +/- 38 MUm and 449 +/- 24 MUm, respectively. The addition of NaF to SDF
      did not show better remineralisation than SDF (p = 0.491). Metallic silver and
      silver chloride were found in Groups 1 and 2. The amide I-to-hydrogen phosphate
      ratios of the four groups were 0.14 +/- 0.02, 0.14 +/- 0.01, 0.29 +/- 0.05 and
      0.49 +/- 0.16, respectively, and the addition of NaF to SDF did not offer better
      protection against collagen exposure than SDF (p = 0.986). The Log10 CFUs of
      Groups 1-4 were 5.75 +/- 0.56, 4.49 +/- 0.57, 6.55 +/- 0.39 and 6.40 +/- 0.38,
      respectively. The presence of NaF reduced the antibacterial effect of SDF (p <
      0.001). The SEM and CLSM images supported the findings. CONCLUSION: Application
      of SDF with or without NaF reduced the demineralisation of dentine caries, but
      SDF exerted stronger inhibition of biofilm growth than SDF with NaF. CLINICAL
      SIGNIFICANCE: NaF varnish affects the antibacterialeffects of SDF, the adjunctive
      application of SDF solution and NaF varnish is not recommended to arrest dentine
      caries in clinic.

PMID- 30114444
TI  - Eye-tracking in dentistry: What do children notice in the dentist?
AB  - OBJECTIVES: To determine, using eye-tracking technology, what children notice the
      most when they look at the dentist. METHODS: A total of 41 children viewed 10
      images of dentists of different genders and ethnicities, and wearing different
      attires, on a computer screen. Due to calibration issues with the eye tracking
      equipment, data from one child was excluded thus resulting in a final sample of
      40 children (21 females; 19 males). Participants were aged 4-12 years. A Tobii X2
      60 eye-tracking camera was used, which follows the location of participants' gaze
      as they look at images on a screen. Areas of interest (AOI's) were pre-defined on
      each image (e.g. eyes, mouth, shirt). Other images were displayed between dentist
      images with no consecutive dentist images displayed. Number of participants to
      fixate and mean length of fixation for each AOI were measured. RESULTS: Visual
      assessment illustrated that the dentist's face had the highest concentration of
      fixations, followed by attire. The circum-oral area has significantly more
      fixations than the eyes. The number of fixations and the mean length of fixation
      were both longer for the face than for the attire, and for the circum-oral area
      compared to the eyes. Distractors such as pens and ties exhibited more and longer
      fixations compared to images without distractors. CONCLUSIONS: Children fixated
      most on the dentist's face particularly the circum-oral area, followed by attire.
      Distractors were able to draw the children's gaze. Importantly, eye-tracking was
      an effective tool in assessing where children look on dentists' images. CLINICAL
      SIGNIFICANCE: This research will provide an understanding of where children focus
      when they look at a dentist. This has not previously been known and will allow
      dentists to modify how they present themselves and interact with child patients.

PMID- 30114446
TI  - Measuring aldehyde emissions in e-cigarettes and the contribution of flavors: A
      response to Khlystov and Samburova.

PMID- 30114445
TI  - RIFM fragrance ingredient safety assessment, 3,3,5-trimethylcyclohexaneacetic
      acid, CAS Registry Number 3213-73-8.

PMID- 30114448
TI  - YouTube videos teaching Arabic speaking population how to perform cardiopulmonary
      resuscitation: The gap between the need and quality!

PMID- 30114447
TI  - RIFM fragrance ingredient safety assessment, dihydroterpinyl acetate, CAS
      registry number 58985-18-5.

PMID- 30114449
TI  - Effect of ascorbic and chondrogenic derived decellularized extracellular matrix
      from mesenchymal stem cells on their proliferation, viability and
      differentiation.
AB  - BACKGROUND: The development and application of biomaterials to promote stem cell
      proliferation and differentiation has undergone major expansion over the last few
      years. Decellularized stem cell matrix (DSCMs) represent bioactive and
      biocompatible materials which achieve similar characteristics of native
      extracellular matrix. DSCMs have given promising outcomes in generating novel
      cell culture substrates mimicking specific niche microenvironments in tissue
      engineering. AIMS: This research aims at producing two different DSCMs obtained
      from adipose derived mesenchymal stem cells and bone marrow mesenchymal stem
      cells, characterize them and evaluate the DSCMs bioactivity on mesenchymal stem
      cells. METHODS: DSCMs were produced using ascorbic or chondrogenic medium, which
      were then used as a scaffold for adipose derived mesenchymal stem cells and bone
      marrow mesenchymal stem cells, respectively. The biological characteristics of
      both types of DSCMs, including cell attachment, morphology, proliferation,
      viability, and chondrogenic and osteogenic differentiation were evaluated and
      compared. RESULTS: Differences between ascorbic derived-DSCMs and chondrogenic
      derived DSCMs were found. Chondrogenic derived-DSCMs remained compact and
      stronger during extraction and this made their handling easier. Ascorbic derived
      DSCMs showed a different protein composition to chondrogenic-DSCMs. Bioactive
      characteristics analyzed were different depending on the cellular origin of DSCM
      and the method used to produce them. CONCLUSIONS: The DSCMs obtained in this work
      constitutes favorable structure- and growth factors providing a microenvironment
      which is very similar to that of native ECM, which results in enhanced biological
      potential of the MSCs and responsiveness to the induction of differentiation. We
      found differences between ascorbic derived-DSCMs and chondrogenic derived DSCMs.
      Our results suggest that the cell source used to produce DSCMs is highly related
      to the bioactive characteristics of DSCMs.

PMID- 30114450
TI  - Evidence for leptin receptor immunoreactivity in the gastrointestinal tract and
      gastric leptin regulation in the rainbow trout (Oncorhynchus mykiss).
AB  - In this study, evidence for leptin receptor (LR) and gastric leptin
      immunoreactivity along the digestive tract of the rainbow trout (Oncorhynchus
      mykiss), is reported. Besides this, the regulation of gastric leptin and its
      transcript by fatty acids was analyzed in vitro. LR was detected mainly in the
      cells of the stomach gastric glands and in the brush border of the epithelium of
      the anterior, middle and distal intestine. In the stomach LR was co-distributed
      with leptin. The regulation of gastric leptin and its transcript by fatty acids
      was analyzed by in vitro incubations. Rabbit polyclonal antibodies anti rainbow
      trout leptin were developed and employed to detect leptin concentration in the
      stomach and in the incubation medium. Stomach slices were incubated with butyric
      (4:0), oleic (18:1n-9), alpha-linolenic (18:3n-3) and arachidonic fatty acids
      (20:4n-6). All fatty acids caused an increase in the protein in both the stomach
      and culture medium, while leptin transcript was not modified. Overall, the
      results confirm the gastric leptin release upon nutritional modulation.

PMID- 30114451
TI  - Reduction-sensitive mixed micelles for selective intracellular drug delivery to
      tumor cells and reversal of multidrug resistance.
AB  - Stimuli-responsive nanocarriers have demonstrated their potentials in optimizing
      chemotherapeutics and anticancer efficacy. In this study, a mixed micelle system
      (THSP) was prepared by combining reduction-sensitive hyaluronic acid
      poly(lactide) (HA-ss-PLA) conjugates and D-alpha-tocopheryl polyethylene glycol
      1000 succinate (TPGS), with objective to achieve multiple functionalities of
      selective intracellular rapid release, active targeting capability and multidrug
      resistance reversal. The mixed micelle possessed desirable particle diameter of
      124.32 nm and high entrapment efficiency at 87.97%. Importantly, the THSP mixed
      micelles demonstrated good stability in systemic circulation and rapidly released
      PTX in intracellular reductive environment. In vitro cellular uptake study and
      cytotoxicity assay indicated that the mixed micelles effectively increased drug
      accumulation in A549 cells and Taxol resistant A549/Taxol cells, and inhibited
      growth of tumor cells. In addition, the redox-responsive THSP micelles
      preferentially accumulated to the tumor site and improved anticancer drug
      activity in vivo, with a TIR of 69.08%. It was concluded that redox-sensitive
      mixed micelles THSP provided a potential vehicle for efficient anticancer drug
      delivery and enhancement in treating MDR tumor in the future.

PMID- 30114452
TI  - Genome-wide patterns of copy number variations in Spodoptera litura.
AB  - Spodoptera litura is a polyphagous pest and can feed on more than 100 species of
      plants, causing great damage to agricultural production. The SNP results showed
      that there were gene exchanges between different regions. To explore the
      variations of larger segments in S. litura genome, we used genome resequencing
      samples from 14 regions of China, India, and Japan to study the copy number
      variations (CNVs). We identified 3976 CNV events and 1581 unique copy number
      variation regions (CNVRs) occupying the 108.5 Mb genome of S. litura. A total of
      5527 genes that overlapped with CNVRs were detected. Selection signal analysis
      identified 19 shared CNVRs and 105 group-specific CNVRs, whose related genes were
      involved in various biological processes in S. litura. We constructed the first
      CNVs map in S. litura genome, and our findings will be valuable for understanding
      the genomic variations and population differences of S. litura.

PMID- 30114453
TI  - Preoperative hypertension increases intraoperative bleeding in patients
      undergoing Mohs micrographic surgery.

PMID- 30114454
TI  - How to navigate dermatology care for the uninsured.

PMID- 30114455
TI  - Angiotensin Converting Enzyme and Subclinical Atherosclerosis in Psoriasis: Is
      there Any Association? A case-control study.

PMID- 30114456
TI  - Growth in the cost of biologics in Medicare beneficiaries, 2013 to 2016.

PMID- 30114457
TI  - The Neurochemistry of Mathematical Genius: Reduced Frontal Excitation/Inhibition
      Balance in an Expert Calculator.
AB  - Alterations in excitatory and inhibitory neurotransmitters (glutamate and GABA,
      respectively) have been found in various neuropsychiatric disorders, but have not
      been examined in individuals with prodigious cognitive abilities. Understanding
      exceptional brain processing is critical for developing biomedical interventions
      for cognitive and neurodevelopmental atypicalities. We tested the 11-fold world
      champion in mental calculation, G.M., and compared his right middle frontal
      gyrus, which has been associated with mathematical prodigy, to four healthy
      control expert calculators, who were not prodigies. We found substantially lower
      frontal glutamate/GABA compared to non-prodigy controls, but not glutamate or
      GABA individually, measured with magnetic resonance spectroscopy. We suggest that
      prefrontal glutamate/GABA is a potential marker of extraordinary cognitive
      skills.

PMID- 30114458
TI  - Greater inflammation and adiposity are associated with lower bone mineral density
      in youth with type 1 diabetes.
AB  - AIMS: The objectives of this study were to investigate relationships of
      inflammation and adiposity with bone mineral density (BMD) in youth with type 1
      diabetes followed prospectively for 18 months. METHODS: Participants were youth
      with type 1 diabetes (n = 136, 8-16.9 years) enrolled in an 18-month behavioral
      nutrition intervention trial. BMD of the total body, subtotal, lumbar spine,
      pelvis leg, arm and rib, percent body fat and percent trunk fat (by dual energy x
      ray absorptiometry) and C-reactive protein (CRP), a marker of inflammation, were
      assessed at baseline, 12 and 18 months. Linear mixed-effects models estimated
      associations of time-varying BMD with time-varying CRP, and with percent body and
      trunk fat. RESULTS: CRP was inversely associated with BMD of the total body,
      pelvis and leg (n = 136). Percent body fat was inversely associated with BMD of
      the total body and pelvis; whereas percent trunk fat was related only to total
      body BMD. CONCLUSIONS: Greater inflammation and adiposity were related to lower
      BMD in youth with type 1 diabetes. Investigating the impact of inflammation and
      adiposity on bone turnover markers could provide insights on mechanisms that
      contribute to this relationship.

PMID- 30114460
TI  - Hallux plantar flexor strength in people with diabetic neuropathy: Validation of
      a simple clinical test.
AB  - AIM: To validate the paper grip test for assessing plantar flexion strength of
      the hallux. METHODS: Plantar flexor strength for 69 people with diabetic
      neuropathy was assessed: (a) using the paper grip test while simultaneously a
      plantar pressure platform quantified the force under the hallux, and (b) using a
      hand-held dynamometer. Following testing, participants were divided into groups:
      (1) passed vs. failed paper grip test (2) males vs. females. Statistical analyses
      determined if differences were evident between the groups and assessed the
      relationship between the paper grip test and the hand-held dynamometer. The
      discrimination ability, sensitivity, specificity, and reproducibility of the
      paper grip test was established. RESULTS: Participants who passed the paper grip
      test demonstrated greater grip force at the hallux than those who failed, and
      they also exhibited greater isometric maximum force during the hand-held
      dynamometry test (p <= 0.05). Grip force for males was significantly higher than
      for females. A moderate positive correlation between the paper grip test and the
      hand-held dynamometer was evident. CONCLUSIONS: In the population examined the
      paper grip test was found to be a valid clinical tool; it offers a non-invasive,
      inexpensive, and quick method to assess plantar flexion strength of the hallux.

PMID- 30114459
TI  - Derivation and external validation of risk algorithms for cerebrovascular
      (re)hospitalisation in patients with type 2 diabetes: Two cohorts study.
AB  - AIMS: Cerebrovascular disease is one of more typical reasons for hospitalisation
      and re-hospitalisation in people with type 2 diabetes. We aimed to derive and
      externally validate two risk prediction algorithms for cerebrovascular
      hospitalisation and re-hospitalisation. METHODS: Two independent cohorts were
      used to derive and externally validate the two risk scores. The development
      cohort comprises 4704 patients with type 2 diabetes registered in 18 general
      practices across Cambridgeshire. The validation cohort includes 1121 type 2
      patients from a post-trial cohort data. Outcomes were cerebrovascular
      hospitalisation within two years and cerebrovascular re-hospitalisation within
      ninety days of the previous cerebrovascular hospitalisation. Logistic regression
      was applied to derive the two risk scores for cerebrovascular hospitalisation and
      re-hospitalisation from development cohort, which were externally validated in
      the validation cohort. RESULTS: The incidence of cerebrovascular hospitalisation
      and re-hospitalisation was 3.76% and 1.46% in the development cohort, and 4.99%
      and 1.87% in the external validation cohort. Age, gender, body mass index, blood
      pressures, and lipid profiles were included in the final model. Model
      discrimination was similar in both cohorts, with all C-statistics > 0.70, and
      very good calibration of observed and predicted individual risks. CONCLUSION: Two
      new risk scores that quantify individual risks of cerebrovascular hospitalisation
      and re-hospitalisation have been well derived and externally validated. Both
      scores are on the basis of a few of clinical measurements that are commonly
      available for patients with type 2 diabetes in primary care settings and could
      work as tools to identify individuals at high risk of cerebrovascular
      hospitalisation and re-hospitalisation.

PMID- 30114461
TI  - Knowledge-based planning for identifying high-risk stereotactic ablative
      radiotherapy treatment plans for lung tumors larger than 5cm.
AB  - PURPOSE: Stereotactic ablative body radiotherapy (SABR) for lung tumors >=5cm,
      can be associated with more toxicity. We investigated the relationship between
      dosimetry and toxicity and used a knowledge-based planning solution to
      retrospectively perform individualized treatment plan quality assurance (QA) with
      the aim of identifying where planning could have been improved. MATERIAL AND
      METHODS: Prior retrospective analysis of 53 patients with primary or recurrent
      non-small cell lung cancer >=5cm, treated with 5 or 8-fraction volumetric
      modulated arc therapy SABR, between 2008-2014, showed 30% >=grade (G) 3 toxicity.
      During this period, several improvements were made to departmental planning
      protocols. RapidPlan was used to compare dosimetry of patients with/without G>=3
      toxicity and a model comprising plans from patients without toxicity and
      compliant with the current planning protocol, was used to quality assure the
      plans from patients who had toxicity. RESULTS: 16/53 patients had G>=3 toxicity,
      including 10 radiation pneumonitis (RP), 3 lung hemorrhage (LH) (1 also had RP)
      and one airway stenosis/atelectasis. RP was again shown to be significantly
      correlated with contralateral and total-lung V5 and mean lung dose. The 4 highest
      contralateral-lung doses belonged to patients with RP. 5/10 clinical plans in
      patients with RP had a contralateral-lung mean dose up to 2.5x higher than the
      knowledge-based plan. For 2/3 patients with LH and one with airway
      stenosis/atelectasis, the clinical plans had the highest proximal bronchial tree
      doses, which was also higher than in plans from the model. In 8 patients with
      G>=3 toxicity, clinical plans had similar dosimetry as the predictions from the
      model. CONCLUSION: A "no-toxicity" RapidPlan model identified the potential for
      dosimetric improvement in nearly 50% of historical treatment plans from patients
      with G>=3 toxicity after SABR for lung tumors>=5cm. Model-based QA may be useful
      for benchmarking treatment planning protocols in routine practice and in clinical
      studies.

PMID- 30114462
TI  - Secondary Neutron Dose from a Dynamic Collimation System During Intracranial
      Pencil Beam Scanning Proton Therapy: A Monte Carlo Investigation.
AB  - Patients receiving pencil beam scanning (PBS) proton therapy with the addition of
      a Dynamic Collimation System (DCS) are potentially subject to additional neutron
      dose from interactions between the incident proton beam and the trimmer blades.
      This study investigates the secondary neutron dose rates for both single field
      uniform dose and intensity modulated proton therapy treatments. Secondary neutron
      dose distributions were calculated for both a dynamically collimated and
      uncollimated, dual-field chordoma treatment plan and compared to previously
      published neutron dose rates from other contemporary scanning treatment
      modalities. Monte Carlo N-Particle transport code was used to track all primary
      and secondary particles generated from nuclear reactions within the DCS during
      treatment through a model of the patient geometry acquired from the CT planning
      dataset. Secondary neutron ambient dose equivalent distributions were calculated
      throughout the patient using a meshgrid with a tally resolution equivalent to
      that of the treatment planning CT. The median healthy brain neutron ambient dose
      equivalent for a dynamically collimated intracranial chordoma treatment plan
      using a DCS was found to be 0.97 mSv/Gy, 1.37 mSv/Gy, and 1.24 mSv/Gy for the
      right lateral single field uniform dose (SFUD) field, apex SFUD field, and
      composite intensity modulated proton therapy distribution from two fields,
      respectively. This was at least 55 % lower than what has been reported for
      uniform scanning modalities with brass apertures but is still an increase in the
      excess relative risk of secondary cancer incidence compared to an uncollimated
      PBS treatment using only a graphite range shifter. Regardless, the secondary
      neutron dose expected from the DCS for these PBS proton therapy treatments
      appears to be on the order of, or below, what is expected for alternative
      collimated proton therapy techniques.

PMID- 30114463
TI  - Clinical responses in cows vaccinated with a developed prototype killed
      Staphylococcus aureus mastitis vaccine.
AB  - Mastitis is an inflammatory condition of the udder that occurs as a result of the
      release of leucocytes into the udder in a response to bacterial invasion. The
      major causes of mastitis are an array of gram positive and negative bacteria,
      however, algae, virus, fungi, mechanical or thermal injury to the gland have also
      been identified as possible causes. Mastitis vaccines are yet to be developed
      using Malaysian local isolate of bacteria. The objective of the present
      experimental trial was to develop a monovalent vaccine against mastitis using S.
      aureus of Malaysian isolate and to evaluate the clinical responses such as
      temperature, respiratory rates and heart rates in vaccinated cows. S. aureus is a
      major causative bacteria in clinical and subclinical types of mastitis in cows.
      Four concentrations of the bacterin (106, 107, 108 and 109 cfu/ml of the local
      isolate of S. aureus) were prepared using Aluminium potassium sulfate adjuvant.
      Thirty cows were grouped into four treatment groups (B, C, D and E) with a fifth
      group as control (A). These groups were vaccinated intramuscularly(IM) with the
      prepared monovalent vaccine and its influence on the vital signs were
      intermittently measured. The mean of rectal temperature was significantly
      different (p? 0.05) at 0hr Post Vaccination [1]" in groups D and E (39.5 +/- 0.15
      degrees C and 39.4 +/- 0.15  degrees C respectively) and at 3 h PV in groups C,
      D and E (39.8 +/- 0.14  degrees C, 39.9 +/- 0.14  degrees C and 40.3 +/- 0.14 
      degrees C respectively) compared to the control group. This indicated a sharp
      increased rectal temperatures between 0hr and 3 h PV in groups C, D and E which
      later declined at 24 h PV. The mean of rectal temperature of group E was
      significantly different (p? 0.05) at weeks 1 and 2 PV (39.87 +/- 0.19  degrees C
      and 39.80 +/- 0.18  degrees C respectively) compared to the control group. The
      mean of heart rate was significantly different (p? 0.05) at week 1 PV in groups D
      and E (83.0 +/- 3.8 beats/minute and 80.0 +/- 3.8  degrees C respectively)
      compared to control. A trending decrease was however observed in heart rates of
      group E from weeks through 4 PV and in group D from weeks 1 through 3 PV. The
      mean of respiratory rates was significantly different (p? 0.05) at week 3 PV in
      group B and D (31.0 +/- 1.2 breaths/minute and 28.0 +/- 1.2 breaths/minute)
      compared to control. In conclusion, this study highlights responses of these
      vital signs due to vaccination against S. aureus causing mastitis in cows. To the
      best of our knowledge the findings of this study adds value to the shallow
      literature on vital signs alterations in cows vaccinated against mastitis as
      elevated levels of temperature and heart rates of group D and E indicated obvious
      response.

PMID- 30114465
TI  - Action-effect contingency modulates the readiness potential.
AB  - The ability to constantly anticipate events in the world is critical to human
      survival. It has been suggested that predictive processing originates from the
      motor system and that incoming sensory inputs can be altered to facilitate
      sensorimotor integration. In the current study, we investigated the role of the
      readiness potentials, i.e. the premotor brain activity registered within the
      fronto-parietal areas, in sensorimotor integration. We recorded EEG data during
      three conditions: a motor condition in which a simple action was required, a
      visual condition in which a visual stimulus was presented on the screen, and a
      visuomotor condition wherein the visual stimulus appeared in response to a button
      press. We measured evoked potentials before the motor action and/or after the
      appearance of the visual stimulus. Anticipating a visual feedback in response to
      a voluntary action modulated the amplitude of the readiness potentials. We also
      found an enhancement in the amplitude of the visual N1 and a reduction in the
      amplitude of the visual P2 when the visual stimulus was induced by the action
      rather than externally generated. Our results suggest that premotor brain
      activity might reflect predictive processes in sensory-motor binding and that the
      readiness potentials may possibly represent a neural marker of these predictive
      mechanisms.

PMID- 30114464
TI  - Gamma-irradiation-killed Streptococcus pneumoniae potently induces the expression
      of IL-6 and IL-8 in human bronchial epithelial cells.
AB  - Streptococcus pneumoniae is a major respiratory pathogen that can cause
      pneumonia, meningitis, and otitis media. Although capsular polysaccharide-based
      vaccines are commercially available, there is a need for broad-spectrum, serotype
      independent, and cost-effective vaccines. Recently, an intranasal vaccine
      formulated with gamma-irradiated nonencapsulated S. pneumoniae whole cells has
      been developed and its immunogenicity is under investigation. Since innate
      immunity influences the subsequent adaptive immunity, in the present study, we
      investigated the immunostimulatory activity of gamma-irradiated S. pneumoniae (r
      SP) in the human bronchial epithelial cell-line, BEAS-2B, by comparing with heat
      inactivated S. pneumoniae (h-SP) and formalin-inactivated S. pneumoniae (f-SP). r
      SP potently induced interleukin (IL)-6 and IL-8 at both mRNA and protein levels
      in a dose- and time-dependent manner, whereas h-SP and f-SP poorly induced them.
      Of note, the mRNA levels of IL-6 and IL-8 were approximately two-fold higher when
      cells were stimulated with 3 * 107 CFU/ml of r-SP for 3 h, while the protein
      levels of IL-6 and IL-8 were approximately five-fold higher after stimulation
      with 3 * 107 CFU/ml of r-SP for 24 h. Furthermore, r-SP exhibited potent
      activation of Toll-like receptor 2 compared with h-SP or f-SP. The expression of
      IL-6 and IL-8 induced by r-SP was mediated through the activation of mitogen
      activated protein kinases. Remarkably, when r-SP was further treated with heat or
      formalin, there was a decrease in the aforementioned activities. Taken together,
      we suggest that r-SP stimulates the human respiratory epithelial cells to produce
      the cytokines IL-6 and IL-8, which might influence the induction of adaptive
      immune responses.

PMID- 30114467
TI  - Cytotoxicity of abietane diterpenoids from Salvia multicaulis towards multidrug
      resistant cancer cells.
AB  - Diterpenoids salvimulticanol (1) and salvimulticaoic acid (2) together with known
      diterpenoid (3-6) were isolated from Salvia multicaulis. Structures were
      elucidated by spectroscopic techniques including HRESIMS as well as 1D-, and 2D
      NMR. In-vitro cytotoxicity was assayed against human cancer cell lines. As
      several metabolites exhibited activity against drug-resistance lines, compounds
      were screened against a panel of human drug-sensitive and multidrug-resistant
      cancer lines. A proposed biosynthetic pathway for these new diterpenoids (1-2) as
      well as the cytotoxic structure-activity relationship of all identified compounds
      were discussed. Compound 1 and 6 showed the most potent cytotoxicity with IC50
      11.58 and 4.13 towards leukemia cell lines CCRF-CEM and CEM-ADR5000,
      respectively.

PMID- 30114466
TI  - Processing of auditory novelty across the cortical hierarchy: An intracranial
      electrophysiology study.
AB  - Under the predictive coding hypothesis, specific spatiotemporal patterns of
      cortical activation are postulated to occur during sensory processing as
      expectations generate feedback predictions and prediction errors generate
      feedforward signals. Establishing experimental evidence for this information flow
      within cortical hierarchy has been difficult, especially in humans, due to
      spatial and temporal limitations of non-invasive measures of cortical activity.
      This study investigated cortical responses to auditory novelty using the
      local/global deviant paradigm, which engages the hierarchical network underlying
      auditory predictive coding over short ('local deviance'; LD) and long ('global
      deviance'; GD) time scales. Electrocorticographic responses to auditory stimuli
      were obtained in neurosurgical patients from regions of interest (ROIs) including
      auditory, auditory-related and prefrontal cortex. LD and GD effects were assayed
      in averaged evoked potential (AEP) and high gamma (70-150 Hz) signals, the former
      likely dominated by local synaptic currents and the latter largely reflecting
      local spiking activity. AEP LD effects were distributed across all ROIs, with
      greatest percentage of significant sites in core and non-core auditory cortex.
      High gamma LD effects were localized primarily to auditory cortex in the superior
      temporal plane and on the lateral surface of the superior temporal gyrus (STG).
      LD effects exhibited progressively longer latencies in core, non-core, auditory
      related and prefrontal cortices, consistent with feedforward signaling. The
      spatial distribution of AEP GD effects overlapped that of LD effects, but high
      gamma GD effects were more restricted to non-core areas. High gamma GD effects
      had shortest latencies in STG and preceded AEP GD effects in most ROIs. This
      latency profile, along with the paucity of high gamma GD effects in the superior
      temporal plane, suggest that the STG plays a prominent role in initiating novelty
      detection signals over long time scales. Thus, the data demonstrate distinct
      patterns of information flow in human cortex associated with auditory novelty
      detection over multiple time scales.

PMID- 30114469
TI  - Bioactivity-guided isolation of beta-Carboline alkaloids with potential anti
      hepatoma effect from Picrasma quassioides (D. Don) Benn.
AB  - beta-Carboline alkaloids in Picrasma quassioides (D. Don) Benn. have been proven
      to possess inhibitory activity against various cancer cells. However, their
      effect on hepatocellular carcinoma and structure-activity relationships (SAR)
      have not been systematically reported. In this work, bioactivity-directed
      fractionation of P. quassioides led to the separation of active fraction A2-2. A
      total of 39 beta-carbolines, including 4 new ones (1-4), were obtained from the
      active fraction. Moreover, all the isolated compounds were identified in the
      active fraction A2-2 by LC-MS. The cytotoxicity on HepG2 and Hep3B cells of all
      compounds was screened by MTT assay, and the SAR were established. The SAR were
      also supported by the apoptosis ratio of HepG2 cells using flow cytometry
      analysis after treatment with potential compounds 1, 2, 9, 10, 12, 29, 36 and 38.
      It suggested that these active compounds caused death of hepatoma cells through
      apoptosis induction. In addition, further study revealed that compounds 12, 29,
      36 significantly activated caspase-3 in HepG2 cells.

PMID- 30114468
TI  - Amaryllidaceae alkaloids from Crinum latifolium with cytotoxic, antimicrobial,
      antioxidant, and anti-inflammatory activities.
AB  - Four novel and potently bioactive Amaryllidaceae alkaloids, 4,8-dimethoxy
      cripowellin C (1), 4,8-dimethoxy-cripowellin D (2), 9-methoxy-cripowellin B (3),
      and 4-methoxy-8-hydroxy-cripowellin B (4), together with one known alkaloid,
      cripowellin C (5) were isolated from the 95% EtOH extract of the bulbs of Crinum
      latifolium. Structural elucidation of all the compounds were performed by
      spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR as well as
      spectroscopy high resolution mass spectrometry. All isolates were in vitro
      evaluated for their cytotoxic activity against seven lung cancer cell lines, in
      addition to antimicrobial activity for eight bacteria, scavenging potential using
      ABTS.+ and DPPH test, and anti-inflammatory activity for Cox-1 and Cox-2 which
      had not previously been tested for crinane-type alkaloids with the cleavage
      between C-1 and C-13. Consequently, alkaloids 1-5 exhibited potent cytotoxicity
      against all of seven tested tumor cell lines with (IC50 < 30 nM). Alkaloids 3 and
      4 displayed the significant antimicrobial activity with IC50 values <0.50 mM and
      antioxidant activity in the ABTS.+ and DPPH test. Additionally, Alkaloids 1-5
      exhibited comparable inhibition of Cox-1 (>64%) and Cox-2 (>90%) with positive
      control.

PMID- 30114470
TI  - 4'-Hydroxy-6,7-methylenedioxy-3-methoxyflavone: A novel flavonoid from Dulacia
      egleri with potential inhibitory activity against cathepsins B and L.
AB  - A new flavone, 4'-hydroxy-6,7-methylenedioxy-3-methoxyflavone 1, and two other
      nucleosides, ribavirin 2 and adenosine 3, were isolated from the leaves of
      Dulacia egleri. The nucleosides were identified by spectroscopic techniques (1D,
      2D-NMR) while the structure of the flavonoid was established by 1D, 2D-NMR
      analysis, including HRESIMS data. The results obtained in the biological assays
      showed that the compound 1 was able to inhibit cathepsins B and L with IC50 of
      14.88 +/- 0.18 MUM and 3.19 +/- 0.07 MUM, respectively. The mechanism of
      inhibition for both enzymes were determined showing to be competitive at
      cathepsin B with Ki = 12.8 +/- 0.6 MUM and non-linear non-competitive with
      positive cooperativity inhibition at cathepsin L with Ki = 322 +/- 33 MUM,
      alphaKi = 133 +/- 15 MUM, betaKi = 5.14 +/- 0.41 MUM and gammaKi = 13.2 +/- 13
      MUM.

PMID- 30114471
TI  - Daily, repeating fluctuations in embryonic incubation temperature alter
      metabolism and growth of Lake whitefish (Coregonus clupeaformis).
AB  - Lake whitefish (Coregonus clupeaformis) utilize overwintering embryonic
      development (up to 180 days), and such stenothermic, cold-water embryos may be
      particularly susceptible to thermal shifts. We incubated whitefish embryos in
      temperature treatments that were constant temperature (2.0 +/- 0.1  degrees C,
      5.0 +/- 0.1  degrees C, and 8.0 +/- 0.1  degrees C; mean +/- SD) or variable
      temperature (VT, mean = 5.0 +/- 0.3  degrees C). In the VT, a daily 2  degrees C
      temperature change followed a continuous pattern throughout development: 2-4-6-8
      6-4-2  degrees C. Hatchling survival proportion from fertilization to hatch was
      significantly impacted by incubation temperature (P < 0.001): 2  degrees C (0.88
      +/- 0.01) and 5  degrees C (0.91 +/- 0.01) showed higher survival than both the
      VT (0.83 +/- 0.02) and 8  degrees C groups (0.15 +/- 0.06), which were
      statistically distinct from each other. Time to hatch (dpf) was significantly
      different across all treatments (P < 0.001): 8  degrees C (68 +/- 2 dpf), VT (111
      +/- 4 dpf), 5  degrees C (116 +/- 4 dpf), 2  degrees C (170 +/- 3 dpf). Likewise,
      hatchling yolk-free dry mass (mg) and total body length (mm) were significantly
      different across all treatments (P < 0.001): 8  degrees C (0.66 +/- 0.08 mg; 11.1
      +/- 0.08 mm), VT (0.97 +/- 0.06 mg; 11.7 +/- 0.05 mm), 5  degrees C (1.07 +/-
      0.03 mg; 12.0 +/- 0.02 mm), 2  degrees C (1.36 +/- 0.04 mg; 12.8 +/- 0.05 mm).
      Oxygen consumption rate (Vo2) was significantly affected by the interaction
      between treatment and measurement temperature (P < 0.001). Hatchling VT whitefish
      showed mean Vo2 that was higher compared to the 2  degrees C group measured at 2 
      degrees C, and lower compared to the 2  degrees C and 5  degrees C group measured
      at 8  degrees C. This study demonstrates that the VT incubation treatment
      produced fewer (increased mortality), smaller embryos that hatched earlier than 2
      degrees C and 5  degrees C embryos. The plasticity of Vo2 for this stenothermic
      incubating fish species under variable incubation conditions reveals a metabolic
      cost to cycling thermal incubation conditions.

PMID- 30114472
TI  - alpha-(phenylselanyl) acetophenone abolishes acute restraint stress induced
      comorbid pain, depression and anxiety-related behaviors in mice.
AB  - alpha-(phenylselanyl) acetophenone (PSAP) is an organoselenium compound that
      presents antidepressive-like and antinociceptive effect in animal models. In this
      study, we evaluate the potential pharmacological effects of PSAP on acute stress
      restriction (ARS)-induced depressive and anxiogenic-like behavior associated with
      hyperalgesia and mechanical allodynia in male adult Swiss mice (25-35 g). The ARS
      is an unavoidable stress situation that was applied for a period of 4 h using an
      individual rodent restraint. Ten min after ARS, the animals were treated with the
      PSAP (10 mg/kg, intragastrically [IG]) or imipramine (IMI, 10 mg/kg, IG) and
      after thirty min they were submitted to the behavioral observations in the forced
      swimming test (FST), sucrose preference test, hot plate, Von-Frey Hair filaments
      (VHF), marble burying test and elevated plus maze (EPM). It was also evaluated
      the levels of plasma corticosterone and some parameters of oxidative stress in
      cortex and hippocampus. The ARS caused a decrease in the latency to the first
      episode of immobility in the FST, the sucrose preference, latency time in the hot
      plate test, frequency of paw withdrawal in the VFH and time spent in the open
      arms of the EPM. ARS also increased the immobility time of mice in the FST, the
      number of marbles buried and enclosed entries number in the EPM. PSAP or IMI
      reversed all these parameters. ARS increased the levels of lipid peroxidation,
      reactive species (RS) and nitrite and nitrate (NOx) levels in cortex and
      hippocampus and the treatment with PSAP or IMI also reduced these parameters,
      demonstrating its effect on the reduction of oxidative stress. In addition, ARS
      also caused an increase in plasma corticosterone levels and PSAP treatment
      reversed this effect. Hence, PSAP exhibited antidepressant-like, anxiolytic-like,
      anti-hyperalgesic and anti-allodynic effect in the ARS model and could be a
      promising molecule to treat these comorbidities.

PMID- 30114473
TI  - Unhealthy gut, unhealthy brain: The role of the intestinal microbiota in
      neurodegenerative diseases.
AB  - The number of bacterial cells living within the human body is approximately equal
      to, or greater than, the total number of human cells. This dynamic population of
      microorganisms, termed the human microbiota, resides mainly within the
      gastrointestinal tract. It is widely accepted that highly diverse and stable
      microbiota promote overall human health. Colonization of the gut with maladaptive
      and pathogenic microbiota, a state also known as dysbiosis, is associated with a
      variety of peripheral diseases ranging from type 2 diabetes mellitus to
      cardiovascular and inflammatory bowel disease. More recently, microbial dysbiosis
      has been associated with a number of brain pathologies, including autism spectrum
      disorder, Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic
      lateral sclerosis (ALS), suggesting a direct or indirect communication between
      intestinal bacteria and the central nervous system (CNS). In this review, we
      illustrate two pathways implicated in the crosstalk between gut microbiota and
      CNS involving 1) the vagus nerve and 2) transmission of signaling molecules
      through the circulatory system and across the blood-brain barrier (BBB). We
      summarize the available evidence of the specific changes in the intestinal
      microbiota, as well as microorganism-induced modifications to intestinal and BBB
      permeability, which have been linked to several neurodegenerative disorders
      including ALS, AD, and PD. Even though each of these diseases arises from unique
      pathogenetic mechanisms, all are characterized, at least in part, by chronic
      neuroinflammation. We provide an interpretation for the substantial evidence that
      healthy intestinal microbiota have the ability to positively regulate the
      neuroimmune responses in the CNS. Even though the evidence is mainly associative,
      it has been suggested that bacterial dysbiosis could contribute to an adverse
      neuroinflammatory state leading to increased risk of neurodegenerative diseases.
      Thus, developing strategies for regulating and maintaining healthy intestinal
      microbiota could be a valid approach for lowering individual risk and prevalence
      of neurodegenerative diseases.

PMID- 30114474
TI  - Athletes versus video game players: A predictive contextual processing study.
AB  - We investigated the effect of abstract and real life meaningful images from
      sports on predictive contextual processing in professional athletes and video
      gamers. EEG was recorded in three groups: professional basketball players (BP),
      professional athletes of individual sports (IA) and experienced action video game
      players (VG). Two recording sessions, each with a different set of visual stimuli
      was presented: either triangles facing left, up, right or down or four images of
      a basketball player throwing a ball. Recording blocks consisted of targets
      preceded by randomized sequences of standards and by sequences including a
      predictive sequence signaling the occurrence of a subsequent target event. The
      gradual increase of P3b amplitudes across the predictive sequence was greater in
      BP compared with VG, when stimuli consisted of real life images of a basketball
      player. For the basketball session, we observed increased local modularity and
      stronger functional connectivity within frontal attentional networks in BP and VG
      compared with IA, during the processing of the predictive sequence. Our findings
      suggest increased top-down attentional allocation, during the processing of
      predictive visual stimuli, in basketball players compared with video gamers and
      individual sports athletes.

PMID- 30114475
TI  - The left central nucleus of the amygdala contributes to mechanical allodynia and
      hyperalgesia following right-sided peripheral nerve injury.
AB  - The left and right central nucleus of the amygdala (CeA) exert asymmetric
      pronociceptive functions. In the setting of a transient noxious stimulus or
      persistent inflammatory pain, neuronal activity increases in the right but not
      left CeA, regardless of side of injury. Much less is known regarding this
      lateralization with respect to the behavioral manifestations of persistent
      neuropathic pain. To address this question, we conducted spared nerve injury
      (SNI) to the left or right hindlimb and then inactivated the left and/or right
      CeA with local microinjection of lidocaine. We evaluated injury-induced
      hypersensitivity with von Frey hairs (mechanical allodynia), a blunt pin
      (mechanical hyperalgesia), and acetone application (cold allodynia). Following
      left-sided SNI, inactivation of the right or bilateral CeA attenuated mechanical
      allodynia and hyperalgesia as well as cold hypersensitivity, while inactivation
      of the left CeA had no effect. Following right-sided SNI, we observed a modality
      dependent effect: mechanical allodynia was attenuated by inactivation of the left
      but neither the right nor bilateral CeA, mechanical hyperalgesia was attenuated
      by left, right and bilateral intra-CeA lidocaine, and cold allodynia was
      unaffected. These data suggest that CeA-mediated control of neuropathic pain is
      not strictly limited to the right CeA as previously assumed. We conclude that
      functional lateralization depends on the type of pain, side of injury and the
      sensory modality, and that the left CeA contributes to mechanical allodynia and
      hyperalgesia after peripheral nerve injury to the right side of the body.

PMID- 30114476
TI  - Up-regulation of ASIC3 expression by beta-estradiol.
AB  - Sex differences occur in nociceptive pain, and estrogens are involved in the sex
      differences. Our previous study shows sex differences exist in acidosis-induced
      nociception in rats, with females being more sensitive than males to acetic acid.
      However, the mechanisms underlying the sex differences remain unclear. We report
      here17beta-estradiol (E2) up-regulates expression of acid-sensing ion channel 3
      (ASIC3), which can mediate the acidosis-induced events. The recombinant plasmid
      of pCDNA3.1-ASIC3-GFP and pCDNA3.1-estrogen receptor alpha (ERalpha) were
      cotransfected to 293 T cells by lipid transfection method. And western blot
      assays showed expression of ASIC3. We found that E2 markedly increases ASIC3
      protein expression in a dose- and time- dependent manner in 293 T cells
      expressing ASIC3 and ERalpha. The up-regulating effect of E2 on ASIC3 protein
      expression is almost completely blocked by the addition of MPP, a specific
      ERalpha antagonist. We also observed that sex differences occur in ASIC3
      expression in rat dorsal root ganglia (DRG) and in acetic acid-induced
      nociceptive responses. ASIC3 protein expression in female rat DRG is higher than
      those in male rat DRG. And female rats are more sensitive to acetic acid-induced
      nociception than males. ASIC3 protein expression in DRG decreases significantly
      after ovariectomy, but not after orchiectomy. These results suggest that E2 up
      regulates ASIC3 expression through ERalpha, which may contribute to sex
      differences in acetic acid-induced nociception.

PMID- 30114477
TI  - NQO1 regulates mitotic progression and response to mitotic stress through
      modulating SIRT2 activity.
AB  - Previous studies have shown that SIRT2 plays a role in mitosis through
      deacetylating specific downstream targets. However, the upstream regulation of
      SIRT2 activity has been relatively unexplored. In this study, we provide evidence
      that NAD(P)H:quinone oxidoreductase 1 (NQO1) interacts with and activates SIRT2
      in an NAD-dependent manner. Strong protein-protein interaction and co
      localization of the two proteins during mitosis is required to maintain an active
      NQO1-SIRT2 axis which is critical for successful completion of mitosis. This is
      evident by the observed delay in mitotic exit in cells upon NQO1 inhibition.
      Mechanistically, this phenotype can be explained by the decrease in APC/C complex
      activity resulting from decreased SIRT2 deacetylation activity. Furthermore, we
      show that this newly established role of NQO1 has an impact on how cancer cells
      may respond to mitotic stress. In this regard, both pharmacologic and genetic
      NQO1 inhibition increases sensitivity to anti-mitotic drugs functioning as
      microtubule poisons by inducing mitotic arrest and allowing cells to accumulate
      cell death signals. Therefore, the significant prognostic value of NQO1 in
      predicting outcome of cancer patients might be explained in part due to the
      functional contribution of NQO1-SIRT2 axis to mitotic stress. Altogether, this
      novel mechanism of action further supports the pleiotropic biological effects
      exerted by NQO1 in addition to its antioxidant function and it might provide the
      basis for expanding the therapeutic potential of NQO1 inhibition towards
      increasing sensitivity to standard treatments.

PMID- 30114479
TI  - Rickettsia massiliae infection after a tick bite on the eyelid.

PMID- 30114478
TI  - N-acetylcysteine ethyl ester as GSH enhancer in human primary endothelial cells:
      A comparative study with other drugs.
AB  - Several drugs are currently in use as glutathione (GSH) enhancers in clinical,
      pre-clinical and experimental research. Here we compare the ability of N
      acetylcysteine (NAC), 2-oxothiazolidine-4-carboxylic acid (OTC), glutathione
      ethyl ester (GSH-EE) and N-acetylcysteine ethyl ester (NACET) to increase the
      intracellular concentration of GSH using primary human umbilical vein endothelial
      cells (HUVEC) as in vitro model. Our experiments highlighted that NACET is
      largely the most efficient molecule in increasing the intracellular levels of
      GSH, cysteine, and gamma-glutamylcysteine. This is because NACET is lipophilic
      and can freely cross plasma membrane but, inside the cell, it is de-esterified to
      the more hydrophilic NAC, which, in turn, is trapped into the cell and slowly
      transformed into cysteine. The higher availability of cysteine is matched by an
      increase in GSH synthesis, cysteine availability being the rate limiting step for
      this reaction. Surprisingly, the increase in GSH concentration was not linear but
      peaked at 0.5 mM NACET and gradually decreased when cells were treated with
      higher concentrations of NACET. We demonstrated that this puzzling ceiling effect
      was due to the fact that NAC released from NACET turned out to be a competitive
      inhibitor of the enzyme glutamate-cysteine ligase, with a Ki value of 3.2 mM. By
      using a cell culture medium lacking of cysteine and methionine, we could
      demonstrate that the slight increase in intracellular levels of cysteine and GSH
      induced by NAC in HUVEC grown in standard medium was due to the reduction of the
      cystine present in the medium itself there rather than to the action of NAC as
      Cys pro-drug. This fact may explain why NAC works well as GSH enhancer at very
      high concentrations in pre-clinical and in vitro studies, whereas it failed in
      most clinical trials.

PMID- 30114480
TI  - Two cases of imported hemorrhagic fever with renal syndrome and systematic review
      of literature.
AB  - Many factors are involved in the epidemiology of hemorrhagic fever with renal
      syndrome (HFRS). Imported cases, as well as those by emigrants, have been
      reported in literature worldwide. Our goal is to document two cases of HFRS,
      imported by two immigrants from two countries, and to make a review of the
      imported HFRS literature data. We performed a systematic literature review
      (PRISMA guidelines) of imported cases of HFRS and herein describe our two
      clinical cases. We found 20 published papers, with 16 of them in English and 4 in
      other languages. Twenty-three patients with travel- or immigration-associated
      HFRS, including our two cases, were identified. We included only papers that were
      in English. The average age of the patients was 35.9 +/- 15.13 years, and the
      ratio of male to female was 8:1. Imported disease from Europe to Europe occurred
      in seven cases, America to Europe occurred in four cases, Europe to America
      occurred in two cases, America to America occurred in two cases, Asia to Asia in
      one case, Asia to Europe in one case, and Europe to Asia in one case. The results
      of the two cited cases are based on the clinical-laboratory, anamnestic, and
      serologic data for both the patients who tested positive for HFRS. Our systematic
      analysis shows that international travelers are important sources of infectious
      diseases. HFRS related to travel and immigration is a rare event. Principal risk
      factors for travelers and immigrants are camping outside recommended areas or
      under unsuitable conditions. In recent years, various publications have shown
      that international travelers and immigrants have expanded the spectrum of
      imported infectious diseases. The literature data show that the actual reported
      numbers of imported case of HFRS are limited.

PMID- 30114481
TI  - Sensorimotor integration in healthy aging: Baseline differences and response to
      sensory training.
AB  - Sensorimotor integration is the process through which somatosensory information
      is incorporated to inform motor output. Given its important behavioural
      implications, understanding the influence of healthy aging on the underlying
      neurophysiology of sensorimotor integration and whether it is modifiable through
      intervention is important. The aims of the current work were to: 1) profile aging
      related differences in sensorimotor integration, and 2) to determine if
      sensorimotor integration in older adults can be modulated in response to sensory
      training. A group of older healthy individuals and younger healthy individuals
      participated in two experimental sessions. First, baseline neurophysiology of
      sensorimotor integration was assessed. Short-latency afferent inhibition,
      afferent facilitation, and long-latency afferent inhibition provided nerve-based
      assessment of sensorimotor integration. Vibration-based measures of sensorimotor
      integration combined vibration of abductor pollicis brevis with single and paired
      pulse transcranial magnetic stimulation techniques. In the second experimental
      session, a 15-min block of sensory training designed to modulate sensorimotor
      integration preceded the same neurophysiological assessment. Results indicate
      that there are aging-related differences in nerve-based measures of sensorimotor
      integration, specifically short- and long-latency afferent inhibition. In
      contrast, there are not aging-related differences when peripheral muscle belly
      vibration is used to probe sensorimotor integration. Following sensory training
      there is a reduction in the cortical response to vibration. These results suggest
      that there is differential aging-related modulation of sensorimotor integration,
      based on the type of afferent information. Additionally, sensorimotor integration
      is modifiable with a single session of sensory training, and this ability for
      neuroplastic change is retained with healthy aging.

PMID- 30114482
TI  - Altered plasmalogen content and fatty acid saturation following epithelial to
      mesenchymal transition in breast epithelial cell lines.
AB  - Epithelial to mesenchymal transition (EMT) is a developmental event characterized
      by phenotypic switching from a polarized epithelial phenotype to an unpolarized
      mesenchymal phenotype. Changes to plasma membrane function accompany EMT yet the
      differences in lipid composition of cells that have undergone EMT are relatively
      unexplored. To address this the lipidome of two cell models of EMT in breast
      epithelial tissue, D492 and HMLE, were analyzed by untargeted LC-MS. Detected
      masses were identified and their abundance was compared through multivariate
      statistical analysis. Considerable concordance was observed in eight lipid
      components between epithelial and mesenchymal cells in both cell models.
      Specifically, an increase in phosphatidylcholine and triacylglycerol were found
      to accompany EMT while phosphatidylcholine- and phosphatidylethanolamine
      plasmalogens, as well as diacylglycerols decreased. The most abundant fatty acid
      lengths were C16 and C18 but mesenchymal cells had on average shorter and more
      unsaturated fatty acids. The results are consistent with enhanced cell mobility
      post EMT and reflect a consequence of oxidative stress pre- and post EMT in
      breast epithelial tissue.

PMID- 30114483
TI  - Successful Hemostasis of Bleeding From Biliary Varices.

PMID- 30114484
TI  - Lowering the Starting Age for Colorectal Cancer Screening to 45 Years: Who Will
      Come...and Should They?

PMID- 30114485
TI  - The Houston Consensus Conference on Testing for Helicobacter pylori Infection.

PMID- 30114486
TI  - Combination Therapy With Vedolizumab and Tofacitinib in a Patient With Ulcerative
      Colitis and Spondyloarthropathy.

PMID- 30114487
TI  - Use of Augmented Reality and Virtual Reality Technologies in Endoscopic Training.

PMID- 30114488
TI  - Spontaneous Seroclearance of Hepatitis B Surface Antigen and Risk of
      Hepatocellular Carcinoma.
AB  - Hepatitis B (HBV) infection is the leading cause of hepatocellular carcinoma
      (HCC) in Asia.1 Hepatitis B surface antigen (HBsAg) seroclearance is considered
      to be one of the most important end points of chronic HBV infection and is
      associated with a reduced risk of HCC.

PMID- 30114489
TI  - A mitochondrial DNA D loop insertion detected almost exclusively in non
      replicating tissues with maternal inheritance across three generations.
AB  - Muscle biopsy identified a possibly pathogenic, mitochondrial DNA D-loop
      insertion, in each of 5 family members from two generations, that was otherwise
      undetectable in most other tissues. The tissue specific regulation of
      heteroplasmy is reflected in an age related increase in muscle heteroplasmy
      level, across the pedigree. This latter finding is in keeping with previous
      reports (e.g. T408A, C16327) but differs in having a very high muscle
      heteroplasmy level, and appears maternally transmitted.

PMID- 30114490
TI  - Consumers' evaluation of imported organic food products: The role of geographical
      distance.
AB  - Country-of-origin (COO) effects and consumer evaluation of organic food products
      are rarely studied in combination. The aim of this study was therefore to
      investigate organic consumers' preferences for imported organic food products
      from different origins and the underlying reasons for these preferences,
      including how consumers' COO preferences depend on the geographical distance to
      the COO. We employed a multi-method, qualitative approach consisting of in-store
      interviews (N = 255) and focus groups (six, N = 38) with organic consumers in
      three German cities located in the north (Hamburg, close to Denmark), west
      (Munster, close to The Netherlands) and south (Munich, close to Austria). The
      interviews confirmed the well-known preference for domestic (also for) organic
      products. It also revealed a preference for geographically close countries as
      origin for imported organic products. The main reason for this preference is the
      perceived negative environmental impact of transportation, followed by trust in
      the country and general country image. Implications for exporters of organic food
      products are discussed, underlining the importance of building trust and
      supporting a positive country image, especially in geographically close export
      markets.

PMID- 30114491
TI  - Transitions on the shopping floor: Investigating the role of Canadian
      supermarkets in alternative protein consumption.
AB  - A transition to a more sustainable diet likely requires substituting proteins of
      animal origin with alternatives like plant-based foods. Yet consumers are not
      regularly consuming alternative protein products, and one potential explanation
      is that the dominant food retail infrastructure is not oriented in favour of
      these foods. This study provides an in-depth exploration of the role of
      supermarkets in plant-based protein consumption in a Canadian food retail
      setting. A mixed-methods approach involving seven supermarket audits, 24 consumer
      interviews, and five key informant interviews was used to explore the in-store
      context for plant-based protein purchasing as well as the forms of "fits" and
      "misfits" between the supermarket's strategies for retailing plant-based protein
      and consumer strategies when shopping for these products. Our findings suggest
      that supermarkets are simultaneously enabling and limiting consumers when it
      comes to alternative protein consumption by increasing the availability of plant
      based options, but assuming basic strategies when it comes to marketing these
      products in-store. We propose several tactics that could facilitate greater
      uptake of these products, including placing plant-based meat and dairy
      substitutes on the same shelves as other meat and dairy products and the devotion
      of more resources to product promotions and the innovation of new varieties. In
      concluding, we contend that efforts to increase society's consumption of
      alternative protein products would greatly benefit from better understanding the
      supermarket's role in mediating this transition.

PMID- 30114493
TI  - Reply to the Editor-TB or not TB: That is the question.

PMID- 30114492
TI  - Eating healthy to impress: How conspicuous consumption, perceived self-control
      motivation, and descriptive normative influence determine functional food
      choices.
AB  - Functional foods are promoted as products that provide specific health benefits
      beyond basic nutrition. While a number of studies show that the motivation behind
      the purchase of such products is oriented towards health concerns, we argue that
      consumers' choice of functional food can also be driven by less health-related
      hedonic or social motives, such as a tendency for indulgence vs. self-control or
      the motivation to impress and show off. This proposition has not been
      systematically and empirically tested before. Hence, the aim of the present study
      is to reveal the relationship between conspicuous consumption, perceived self
      control motivation, susceptibility to descriptive normative influence and the
      consumption of functional foods. Our results (N = 900) suggest that conspicuous
      consumption and susceptibility to descriptive normative influence are positively
      associated with functional food distinctiveness evaluation while perceived self
      control motivation is negatively associated with such evaluation. Moreover,
      results further revealed the indirect effects of susceptibility to descriptive
      normative influence, conspicuous consumption and perceived self-control
      motivation on self-reported purchase rates of functional foods via the functional
      food distinctiveness evaluation. The findings support the relevance of social and
      hedonic motives for policy makers and marketers in the functional foods industry
      for marketing and health promotion.

PMID- 30114494
TI  - Letter to the Editor-TB or not TB? That is the question.

PMID- 30114496
TI  - Dropped Bifurcation Technique for Femoral Endarterectomy.
AB  - Femoral endarterectomy is an established procedure with excellent outcomes.
      Variations in performing this operation generally reflect the extension of
      pathology into the superficial and deep femoral arteries. For these instances, we
      developed a technique not previously described that enables continued flow to the
      superficial and deep femoral arteries and facilitates patch placement.

PMID- 30114495
TI  - Improving emergency surgical care for patients with right iliac fossa pain at a
      regional scale: A quality improvement study using the Supported Champions
      implementation strategy.
AB  - INTRODUCTION: Methods to improve clinical systems safety suffer from significant
      difficulties in implementation and scaling up. We used an upscaling
      implementation strategy entitled Supported Champions in a quality and safety
      improvement programme for emergency surgery at regional level, focusing on
      patients with right iliac fossa pain. METHODS: A before-after study was conducted
      across four acute NHS Trusts: A 6 month intervention phase was preceded and
      followed by 3 months of data collection. An established Human Factors
      intervention was led at each Trust by a small group of staff selected as
      Champions. Champions received training in teamwork and systems improvement and
      were supported by Human Factors experts. The primary improvement aim was to
      expedite surgery for patients with sepsis, using Royal College of Surgeons
      emergency surgery guidelines as the measure. Additional outcomes studied included
      length of inpatient stay and 30-day readmission rates. RESULTS: Breaches of RCS
      urgency guidelines decreased markedly from 13.7% of operated patients pre
      intervention to 3.5% post-intervention (p = 0.000). Mean time from booking to
      incision decreased in three of the four sites, whilst median length of stay
      increased in 3 of 4. Overall 30-day readmission rate remained stable (7.84% pre
      intervention versus 7.31% post-intervention, p = 0.959). DISCUSSION: The
      Supported Champions model allowed all surgical teams to reduce delay for septic
      patients by more than 50%, using distinct Quality Improvement strategies to
      address local issues. Improvement was implemented in 4 diverse settings with a
      quarter of the level of expert input previously used in a single hospital.

PMID- 30114497
TI  - The Transposed Femoral Vein Fistula: The Native Choice in Desperate Vascular
      Access.
AB  - BACKGROUND: This is a review of our experience in creating transposed femoral
      vein (TFV) fistulas and some of the lessons we have learnt while performing this
      challenging procedure over the last 5 years. METHODS: This is retrospective
      review of patients who underwent TFV fistula formation between January 2013 and
      December 2017. RESULTS: Fifteen patients underwent FV fistula formation with 4
      cases being excluded from analysis. Median follow-up was 1.17 years
      (interquartile range 0.19-3.59 years). Primary and primary-assisted patency rates
      were 75% and 100% at 6 months, respectively, and 66.7% and 100% at 1 year.
      CONCLUSIONS: Our patient group showed good fistula patency at 1 year and did not
      experience any incidence of ischemic steal syndrome. We believe this to be due to
      careful preoperative patient assessment and meticulous surgical technique. Our
      experience suggests that such procedures should be performed by surgeons with
      vascular expertise wherever possible to reduce the incidence of complications.

PMID- 30114498
TI  - Should the Histological Examination Be Used in the Diagnosis of Aneurysms of the
      Dorsalis Pedis Artery? A Case Report and Review of the Literature.
AB  - Aneurysms of the dorsalis pedis artery are rare, and they are not commonly
      examined histologically. In general, pseudoaneurysms are thought to be more
      common than true aneurysms of the dorsalis pedis artery. We present a patient
      with a true aneurysm of the dorsalis pedis artery, which was initially diagnosed
      as a pseudoaneurysm that had developed because of a blunt trauma of the ankle.
      However, the intraoperative appearance and histological examination both
      confirmed a true aneurysm. Our experiences seem to confirm that postoperative
      histological examination is needed to distinguish pseudoaneurysms from true
      aneurysms of the dorsalis pedis artery. The treatment of aneurysms of the
      dorsalis pedis artery is simple and includes resection, which completely relieves
      the symptoms; few patients need vascular reconstructions.

PMID- 30114499
TI  - A 3D Printed Aortic Arch Template to Facilitate Decision-Making Regarding the Use
      of an Externalized Transapical Wire during Thoracic Endovascular Aneurysm Repair.
AB  - Thoracic endovascular aortic repair (TEVAR) is an established treatment option,
      although some anatomical challenges require a through-and-through wire technique,
      and subsequently transapical access via minithoracotomy can be required. It is
      clear that an objective tool to facilitate decision-making is needed. A 3D print
      of a severely angulated aortic arch was used as a template to advance a stent
      graft, and this was achieved after pulling the top of the wire. This simulation
      assisted in decision-making relating to transapical access with a wire
      externalization. A 3D aortic print could be used in advance to simulate the TEVAR
      procedure and facilitate any other decisions regarding additional transapical
      access.

PMID- 30114500
TI  - Endovascular Repair of Iliac Vein Laceration Associated with Complex Pelvic
      Fracture.
AB  - BACKGROUND: Iliac vein injury associated with pelvic fracture due to blunt trauma
      is an uncommon and difficult diagnosis but a life-threatening condition which
      often requires an emergent management. Although open repair has been
      traditionally used as the treatment of choice in unstable patients, it is
      controversial, given the difficulty due to injured vessel exposure in patients
      with significant retroperitoneal hematoma as well as tamponade effect loss
      associated with laparotomy. We present a challenging case of iliac vein
      laceration successfully treated by placement of a self-expanding covered stent.
      METHODS: A 15-year-old male was hemodynamically unstable and was transferred to
      our emergency department after a severe polytrauma due to a motorcycle accident.
      Contrast-enhanced computed tomography showed a left external iliac vein
      laceration with active bleeding and retroperitoneal hematoma as well as complex
      pelvic and left supracondylar femoral fractures. A 13 * 100 mm self-expanding
      covered stent was successfully deployed through duplex ultrasound-guided
      percutaneous approach of both femoral veins. RESULTS: The patient's blood
      pressure was normalized as soon as the stent graft was placed, and then femoral
      fracture was reduced and fixed. At 12-month follow-up, the patient remained
      asymptomatic, and stent-graft patency was confirmed. CONCLUSIONS: Covered stent
      graft placement can be an effective and rapid treatment for life-threatening
      iliac vein injury.

PMID- 30114501
TI  - The Progression of Billowing of Endologix AFX2(r) Abdominal Aortic Aneurysm
      Device as a Precursor for the Rupture of an Abdominal Aortic Aneurysm.
AB  - Despite recent publications indicating billowing (aneurysmal degeneration of the
      outer fabric material manifesting as a bulging sac of contained contrast due to
      weakening of the fabric material between the metal struts) as a benign finding,
      we present a unique case of billowing that resulted in aneurysmal rupture with
      the AFX2(r) stent graft (Endologix, Inc., Irvine, CA). AFX2(r) consists of an
      inner metallic endoskeleton with multiple metallic struts covered by a
      polytetrafluoroethylene graft fabric. It allows the flow of blood or contrast
      beyond the border of the metallic endoskeleton without evidence of endoleak or
      rupture secondary to the outer cover being anchored to the endoskeleton with
      polypropylene sutures only at the proximal and distal ends. Our report raises the
      concern that although billowing may be a relatively common manifestation with
      Endologix stent grafts, clinicians have to be diligent as the phenomenon may
      progress to abdominal aortic aneurysm rupture.

PMID- 30114502
TI  - Endovascular Treatment of Claudication due to Isolated Internal Iliac Artery
      Occlusive Disease.
AB  - Aortoiliac occlusive disease is a common cause of lower extremity claudication.
      Patients are typically found to have diminished femoral pulses and abnormal
      noninvasive vascular studies of the lower extremities. Isolated lesions of the
      internal iliac arteries are much less commonly treated but can cause similar
      claudication symptoms in the buttocks, hips, or thighs. Occlusive disease in the
      internal iliac artery is more challenging to diagnose because the lower extremity
      pulses and vascular studies can be normal. This may falsely steer the diagnosis
      away from a vascular etiology. We present a case of disabling buttock
      claudication in a patient with normal pulses and isolated ipsilateral internal
      iliac artery stenosis. This was treated successfully with drug-eluting balloon
      angioplasty. We review the literature for similar cases of isolated internal
      iliac artery occlusive disease and summarize the disease characteristics and
      treatment modalities.

PMID- 30114503
TI  - Updated Clinical and Radiological Classification of Lower Limb Atherosclerotic
      Disease.
AB  - Lower limb atherosclerotic disease has classically been classified as acute or
      chronic; however, this is an evolving process that has a wide spectrum of
      clinical and imaging aspects. Owing to the evolvement of endovascular and imaging
      techniques, we have now garnered new information regarding the pathophysiology
      and behavior of atherosclerotic disease, also in response to endovascular and
      surgical techniques. Clinical presentation can actually be classified according
      to the time of presentation, ranging from acute (<2 weeks) and subacute (from 2
      weeks to 3 months) to chronic (over 3 months) and acute/subacute on underlying
      chronic disease. Imaging characteristics such as the presence of thrombus, number
      of collaterals, and target vessel wall features may help in defining the correct
      type of atherosclerotic lesion, triggering the appropriate treatment strategy.
      Clinical and imaging characteristics of those different stages are complex and
      not systematically addressed by current guidelines, that do not show any specific
      recommendations for imaging pathways/characteristics or treatment. This review
      illustrates the clinical and imaging characteristics of the different stages of
      lower limb atherosclerotic disease and related treatment options.

PMID- 30114504
TI  - Revascularization with Obturator or Hemi-neoaortoiliac System for Partial Aortic
      Graft Infections.
AB  - BACKGROUND: Infections of isolated limbs of prosthetic grafts are challenging.
      Management can be morbid, involving partial or complete removal of all prosthetic
      material followed by aortic reconstruction. More limited resections of only
      infected material and reconstruction of the affected iliac limb has been reported
      as a viable surgical option. We review 2 academic institution's experiences
      treating limited aortic graft infections by obturator canal bypass (OCB) or hemi
      neoaortoiliac system (H-NAIS). METHODS: A retrospective review of OCB at one
      institution between 1995 and 2013 and H-NAIS at the other institution between
      2003 and 2014 was conducted. Demographics, comorbidities, and postoperative and
      medium-term events were recorded. Outcomes were patency, limb salvage, graft
      preservation without reinfection, and survival. RESULTS: OCB was performed in 18
      limbs and H-NAIS in 34 limbs. The OCB group had a higher prevalence of cancer
      (40% vs. 10%; P = 0.04). The most common treatment indication was infection of an
      aortobifemoral bypass limb in both groups. No differences were seen in overall
      graft infection, with one patient suffering a late graft reinfection (6% of OCB
      versus 0% in H-NAIS; P = 0.35). There were no perioperative deaths in either
      group. Regarding major adverse limb events, there were no amputations performed
      in the perioperative period in either group. The most frequent organism cultured
      in both OCB and H-NAIS was Staphylococcus aureus. Surgery duration was similar
      between the groups (OCB 379 +/- 115 minutes vs. H-NAIS 370 +/- 137 minutes; P =
      0.8) as was the length of stay (OCB 10.5 +/- 5.3 days vs. H-NAIS 12.4 +/- 10.6
      days; P = 0.4). At 36 months, there was no difference in primary patency (OCB 45%
      vs. H-NAIS 63%; P = 0.7), primary-assisted patency (OCB 51% vs. H-NAIS 61%; P =
      0.5), or secondary patency (OCB 68% vs. H-NAIS 63%; P = 0.6) between the groups.
      Endovascular and open reinterventions occurred more frequently in OCB than in H
      NAIS (61.1% vs. 23.5%; P = 0.007). There were no differences in overall survival
      (OCB 83% vs. H-NAIS 81%; P = 0.6), and no significant difference in amputation
      rate was seen during the follow-up period (OCB 17% vs. H-NAIS 6%; P = 0.35).
      CONCLUSIONS: OCB and H-NAIS are effective strategies for treatment of limited
      aortic graft infections with reasonable patency, survival, and limb salvage at
      medium-term follow-up. Prudent patient selection and institutional experience
      with aortic graft infection treatment leads to good outcomes with lifelong follow
      up recommended. Further study of the optimal treatment strategy for this complex
      group of patients is needed.

PMID- 30114505
TI  - Quantification of Daily Physical Activity and Sedentary Behavior of Claudicating
      Patients.
AB  - BACKGROUND: Claudication is the most common manifestation of peripheral artery
      disease (PAD), producing significant ambulatory compromise. Limited information
      exists on the routine physical activity of claudicating patients. Our objective
      was to record the intensity/time profiles of physical activity and the timing and
      duration of sedentary behavior of a sample of community-dwelling claudicating
      patients. METHODS: Forty-four claudicating patients referred to our vascular
      clinic were recruited. Physical activity was recorded using the ActiGraph GT1M
      activity monitor. The Actigraph monitor is a lightweight instrument designed to
      measure human movement through changes in acceleration, measured as counts over 1
      minute time periods. Data from 7 consecutive days were used for the calculations.
      We processed the data using the ActiLife software program. RESULTS: The average
      daily activity of the claudicating patients shows a steady increase beginning
      approximately 05:30 AM until a peak plateau from approximately 10:00 AM to 01:30
      PM followed by a steady decrease until approximately 09:30 PM, when a sustained
      period of inactivity begins. The average claudicating patient takes 3586 steps
      per day at an average intensity of 1.77 metabolic equivalents of task (METs, a
      physiological measure expressing the energy cost of physical activities). Average
      physical activity intensity and peak intensity fluctuate very little during the
      day, and they rarely exceed the level of light activity (light = <3 METs maximum
      effort, such as casual walking or light housework). During awake time,
      approximately 7 hours are spent in sedentary behaviors (<1.5 METs), and sedentary
      time is spread throughout the day mostly in short intervals between periods of
      low-energy activity. CONCLUSIONS: Our study objectively demonstrates the reduced
      physical activity of claudicating patients and documents physical
      activity/duration profiles throughout the day. The intensity of the physical
      activity of the average claudicating patient fluctuates very little during the
      day and rarely exceeds a light intensity level. Claudicating patients spend
      approximately half of their awake time in sedentary behavior and when they walk
      they do it in short bursts followed by several minutes of rest. We anticipate
      that changes in routine physical activity/duration profiles of patients with PAD
      will provide relevant, sensitive, and direct measures of the effectiveness of
      therapeutic interventions.

PMID- 30114506
TI  - Successful Hybrid Zone 0 Landing Thoracic Endovascular Aortic Repair for
      Ascending Aortic Pseudoaneurysm after Bentall Procedure and Coronary Artery
      Bypass Grafting in Takayasu Arteritis.
AB  - Pseudoaneurysm at the suture line is one of the most common complications in
      aortic surgery for Takayasu arteritis (TA) and is associated with a high
      mortality rate. A 52-year-old man with TA, who previously underwent the Bentall
      procedure and 2 redo surgeries for coronary artery obstruction and a
      pseudoaneurysm of a coronary button, was diagnosed with an anastomotic
      pseudoaneurysm in the ascending aorta. Hybrid zone 0 debranching thoracic
      endovascular aortic repair was performed, and the patient was discharged
      uneventfully on postoperative day 8.

PMID- 30114507
TI  - Failure of Sandwich Technique for Thoracoabdominal Aneurysm Treated with Custom
      Made Fenestrated Endograft.
AB  - BACKGROUND: Custom-made fenestrated and branched endografts are considered the
      gold standard devices for thoracoabdominal repair, with lower perioperative
      mortality and morbidities than open surgical repair. Although they are not
      feasible in urgent and emergent settings, in which sandwich techniques are often
      necessary, custom-made devices can still be used as bail-out options to correct
      late complications such as high-flow endoleaks, as shown in this case report.
      METHODS: A complex, symptomatic thoracoabdominal aneurysm, unsuitable for open
      repair, was treated by sandwich technique on the celiac trunk despite having a
      short distal neck. After the finding of a high-flow type IB endoleak during
      postoperative follow-up, reintervention was planned with a custom-made endograft
      with a distal scallop, to preserve patency of the superior mesenteric artery.
      RESULTS: The procedure achieved technical success, with complete exclusion of the
      aneurysm and patency of all the visceral arteries. CONCLUSIONS: Bail-out
      endovascular repair with custom-made endografts after failure of parallel graft
      repair of thoracoabdominal aneurysms is a valuable treatment option preventing
      the risks related to an open conversion.

PMID- 30114508
TI  - Post-stroke losartan and captopril treatments arrest hemorrhagic expansion in
      SHRsp without lowering blood pressure.
AB  - We assessed the ability of poststroke losartan and captopril treatment to
      attenuate hematoma expansion and plasma extravasation after intracerebral
      hemorrhagic stroke in Kyoto-Wistar stroke-prone hypertensive rats (SHRsp).
      Cerebrum volume, herniation and surface areas exhibiting new and old hemorrhages
      and albumin extravasation were measured prior to and after stroke and following
      30 and 60 days of post-stroke losartan or captopril treatment in Evans Blue dye
      perfused brains. Lesion morphology was studied in serial sections. Losartan or
      captopril treatment initiated at stroke prevented death for 60 days without
      lowering BP. Stroke onset was associated with the development and subsequent
      expansion of cerebrum volume, herniation, hematoma and plasma albumin
      extravasation. Losartan arrested cerebral volume expansion and herniation, and
      produced the virtual disappearance of hematoma and plasma albumin extravasation
      after 60 days. Captopril treatment equally attenuated cerebral herniation and
      hematoma expansion but was less effective in stopping albumin extravasation and
      allowed cerebrum volume to increase to post-stroke levels after 60 days of
      treatment. Both treatments resolved hematomas into cortical fluid filled spaces
      and prevented new hemorrhage formation. We believe that the treatments attenuated
      death after stroke by inhibiting hemorrhagic expansion through non-pressure
      related physiological changes mediated by the inhibition of the renin-angiotensin
      system.

PMID- 30114509
TI  - Asiatic acid stabilizes cytoskeletal proteins and prevents TNF-alpha-induced
      disorganization of cell-cell junctions in human aortic endothelial cells.
AB  - Endothelial hyperpermeability represents an initiating step in early
      atherosclerosis and it often occurs as a result of endothelial barrier
      dysfunction. Asiatic acid, a major triterpene isolated from Centella asiatica
      (L.) Urban, has previously been demonstrated to protect against tumor necrosis
      factor (TNF)-alpha-induced endothelial barrier dysfunction. The present study
      aimed to investigate the mechanisms underlying the barrier protective effect of
      asiatic acid in human aortic endothelial cells (HAECs). The localization of F
      actin, diphosphorylated myosin light chain (diphospho-MLC), adherens junctions
      (AJs) and tight junctions (TJs) was studied using immunocytochemistry techniques
      and confocal microscopy. Their total protein expressions were examined using
      western blot analysis. The endothelial permeability was assessed using In Vitro
      Vascular Permeability Assay kits. In addition, intracellular redistribution of
      the junctional proteins was evaluated using subcellular fractionation kits. We
      show that asiatic acid stabilized F-actin and diphospho-MLC at the cell periphery
      and prevented their rearrangement stimulated by TNF-alpha. However, asiatic acid
      failed to attenuate cytochalasin D-induced increased permeability. Besides,
      asiatic acid abrogated TNF-alpha-induced structural reorganization of vascular
      endothelial (VE)-cadherin and beta-catenin by preserving their reticulum
      structures at cell-cell contact areas. In addition, asiatic acid also inhibited
      TNF-alpha-induced redistribution of occludin and zona occludens (ZO)-1 in
      different subcellular fractions. In conclusion, the barrier-stabilizing effect of
      asiatic acid might be associated with preservation of AJs and prevention of TJ
      redistribution caused by TNF-alpha. This study provides evidence to support the
      potential use of asiatic acid in the prevention of early atherosclerosis, which
      is initiated by endothelial barrier dysfunction.

PMID- 30114510
TI  - Quantitative proteomics using tandem mass tags in relation to the acute phase
      protein response in chicken challenged with Escherichia coli lipopolysaccharide
      endotoxin.
AB  - : The inflammatory response in chickens (Gallus Gallus domesticus) is an integral
      part of the bird's response to infection. Detailing proteomic changes occurring
      during infection would be beneficial to the poultry industry, offering
      opportunities for comparative pathophysiological analysis. The objective of this
      study was to quantify the changes in the plasma proteome in chickens challenged
      with lipopolysaccharide (LPS), a bacterial endotoxin known to stimulate the host
      innate immune system. Plasma from chicken (N = 6) challenged with Escherichia
      coli (LPS) (2 mg/kg body weight) was collected pre (0 h) and at 12, 24, 48, and
      72 h post-injection along with plasma from a control group (N = 6) challenged
      with sterile saline. Samples were analysed by a quantitative Tandem Mass Tags
      approach using a Q-Exactive-Plus mass-spectrometer. Identification and relative
      quantification were performed using Proteome Discoverer, and data were analysed
      using R. Gene Ontology terms were analysed by Cytoscape based on the Gallus
      gallus database. Finally, 87 significantly regulated proteins were found,
      including serum-amyloid-A, ovotransferrin and alpha-1-acid-glycoprotein, showing
      a significant effect of time post-injection in the LPS-treated group. Different
      pathways related with protein activation cascade and heterotopic cell-cell
      adhesion were affected by LPS-challenge. LPS-challenged chickens demonstrate
      significant changes to the plasma proteome with both increases and decreases of
      individual proteins within 12 h of challenge. SIGNIFICANCE: The injection of
      chicken with bacterial lipopolysaccharide followed by sequential plasma and
      clinical analysis of the bird, is a long established and a widely used model for
      inflammation and infection studies. This study, utilising and combining proteomic
      and immunoassay analysis with bioinformatic analysis, revealed that several
      biological pathways are modulated during this early period of inflammation. In
      addition, proteins with biomarker potential were identified and successfully
      validated. This experimental model also demonstrated potential for
      pathophysiological mechanism investigation and as an inflammatory model for
      biomedical research. There is, despite plasma being an easily accessible
      biological matrix which is representative of the health status of the bird,
      scarce data on the chicken plasma proteome. This research makes a positive
      contribution to the current field, generating significant data for continuing
      comparative analysis.

PMID- 30114511
TI  - Knufia epidermidis: a rare finding in a paediatric dermatological sample.

PMID- 30114513
TI  - Building atomic models based on near atomic resolution cryoEM maps with existing
      tools.
AB  - The EMDataBank Validation Challenge was a challenging task for students newly
      introduced to the cryoEM and molecular modeling fields. However, the competition
      provided an effective space for student modelers to discover and explore the
      potentials of atomic modeling and refinement by practicing on published atomic
      structures. Here, by employing manual molecular modeling programs such as Coot,
      Phenix, and Chimera, we have regularized and improved three targets. The T20S
      proteasome and TRPV1 ion channel allowed us to broaden our understanding of these
      modeling techniques while the 70S ribosome served as a challenge to test the
      limits of our abilities. We were successful in our efforts to improve each of the
      models and provide here our cohesive methodology for de novo modeling with and
      without homology models, which may serve as a starting point for other
      undergraduates and researchers just entering the realm of cryoEM. Additionally,
      we provide some constructive criticism to facilitate the introduction of said
      undergraduates and researchers into cryoEM in the future.

PMID- 30114512
TI  - The first single particle analysis Map Challenge: A summary of the assessments.
AB  - The recent successes of cryo-electron microscopy fostered great expectation of
      solving many new and previously recalcitrant biomolecular structures. However, it
      also brings with it the danger of compromising the validity of the outcomes if
      not done properly. The Map Challenge is a first step in assessing the state of
      the art and to shape future developments in data processing. The organizers
      presented seven cases for single particle reconstruction, and 27 members of the
      community responded with 66 submissions. Seven groups analyzed these submissions,
      resulting in several assessment reports, summarized here. We devised a range of
      analyses to evaluate the submitted maps, including visual impressions, Fourier
      shell correlation, pairwise similarity and interpretation through modeling.
      Unfortunately, we did not find strong trends. We ascribe this to the complexity
      of the challenge, dealing with multiple cases, software packages and processing
      approaches. This puts the user in the spotlight, where his/her choices becomes
      the determinant of map quality. The future focus should therefore be on
      promulgating best practices and encapsulating these in the software. Such
      practices include adherence to validation principles, most notably the processing
      of independent sets, proper resolution-limited alignment, appropriate masking and
      map sharpening. We consider the Map Challenge to be a highly valuable exercise
      that should be repeated frequently or on an ongoing basis.

PMID- 30114514
TI  - Bone and parietal anterior iliac crest reconstruction for trans-iliac hernia
      after tricortical graft harvesting: An original technique.
AB  - Tricortical cortico-cancellous bone allografts from the anterior iliac crest are
      routinely used in revision arthroplasty and to treat non-union. Trans-iliac
      herniation (TIH) has been reported as an exceptional complication after extensive
      graft harvesting. The various reconstruction techniques include isolated parietal
      reconstruction and combined parietal and bone reconstruction using allografts or
      a spacer to reconstruct the bone defect. No previous study has evaluated a
      combined reconstruction technique involving both bone reconstruction with a
      titanium plate and abdominal wall reconstruction with a parietal reinforcement
      prosthesis. This technical note describes the evaluation of an original combined
      reconstruction technique used after failure of isolated parietal reconstruction
      to treat TIH. Through a direct approach to the anterior iliac crest, the bone
      defect was repaired using a flexible titanium cranio-facial reconstruction plate
      and the abdominal wall defect using a polypropylene/poliglecaprone parietal
      reinforcement prosthesis. This original technique was demonstrated to be
      effective for treating TIH, with no recurrence after 2.5 years of follow-up. In
      addition, this technique involves no added morbidity related, for instance, to
      allograft using or spacer migration.

PMID- 30114516
TI  - Protective effects of Paederia scandens extract on rheumatoid arthritis mouse
      model by modulating gut microbiota.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Paederia scandens (Lour.) Merr. (P. scandens) has
      been traditionally used to treat the pain of rheumatism. AIM OF THE STUDY: The
      purpose of this study was to investigate the possible influences of P. scandens
      on the progression of rheumatoid arthritis (RA), inflammatory responses and gut
      bacterial communities in RA mouse model. MATERIALS AND METHODS: collagen-induced
      arthritis (CIA) mice were orally administered with P. scandens extract (PSE) for
      24 days. Then, pro-inflammatory cytokine levels in the serum were measured, and
      gut microbiota was examined with Illumina HiSeq. RESULTS: Compared with the
      vehicle group, PSE significantly inhibited paw swelling and reduced arthritis
      score. Histological examination of ankle soft tissue of demonstrated PSE
      effectively inhibited the tissue fibrosis and inflammatory cell infiltration. The
      increased serum levels of TNF-alpha, IL-1beta, IL-6, IL-7, and IL-23 in RA mice
      were significantly suppressed by PSE. Moreover, PSE treatment help restore gut
      microbial ecosystem altered in RA mice including decreasing relative abundance of
      inflammatory related microorganisms, Desulfovibrio, Mucispirillum, Helicobacter,
      and Lachnospiraceae. CONCLUSION: These results suggest that PSE has therapeutic
      effects in RA mice with CIA, showing the potential as anti-arthritis reagent.

PMID- 30114515
TI  - Evaluation of the toxicity and anti-inflammatory activities of the infusion of
      leaves of Campomanesia guazumifolia (Cambess.) O. Berg.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Some species of Campomanesia are used in the folk
      medicine due to anti-inflammatory, anti-diarrheal, anti-diabetes and
      hypercholesterolemic. However studies with Campomanesia guazumifolia (Cambess.)
      O. Berg. are scarce. AIM OF THE STUDY: This study investigated the anti
      inflammatory activity and toxicological profile of infusion obtained from leaves
      of Campomanesia guazumifolia in mice. MATERIALS AND METHODS: Leaves infusion of
      C. guazumifolia was obtained in the proportion of 20 g/L (leaves/water) at 95-100
      degrees C for 10 min in an enclosed container. The acute toxicity of the leaves
      infusion of C. guazumifolia lyophilized (ICG) was assessed by oral administration
      to female mice at doses of 500, 1000, 2000, and 5000 mg/kg, and the general
      behavior and toxic symptoms were observed for 14 days. In the subacute toxicity
      model, female mice were treated orally with the ICG (250, 500, and 1000 mg/kg)
      during 28 days, and biochemical, toxic signs and the estrous cycle were
      evaluated. The anti-inflammatory activity of the ICG (70, 300 and 700 mg/kg) was
      analyzed using carrageenan-induced pleurisy and inflammatory paw (mechanical and
      thermal hyperalgesia). RESULTS: Three flavonoids glycosylated and a
      cyclohexanecarboxylic acid were identified in the ICG: quercetin pentose,
      quercetin deoxyhexoside, myricetin deoxyhexoside and quinic acid. No clinical
      signs of acute toxicity were observed, suggesting that the LD50 (Lethal Dose) is
      above 5000 mg/kg. Subacute exposure of mice to the ICG did not change
      significantly the hematological and biochemical parameters as well as histology
      of organs. The ICG increased the duration of estrous cycle in all phases, showing
      anti-inflammatory potential by decreasing leukocyte migration, extravasation
      protein in the pleural cavity and antiedematogenic activity. The ICG treatment at
      a dose of 700 mg/kg decreased the mechanical hyperalgesia, while at doses of 300
      mg/kg and 700 mg/kg, decreased the sensitivity to the cold. CONCLUSION: The
      results evidenced the anti-inflammatory potential with low toxicity of infusion
      of the leaves of C. guazumifolia, supporting the popular use of this species.

PMID- 30114517
TI  - Therapeutic effects of Caesalpinia minax Hance on complete Freund's adjuvant
      (CFA)-induced arthritis and the anti-inflammatory activity of cassane diterpenes
      as main active components.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Caesalpinia minax Hance called 'Ku-Shi
      Lian' (KSL) in China have been used as Zhuang or Dai folk medicines for treatment
      of common cold, fever, rheumatoid arthritis and dysentery for hundred years. AIM
      OF THE STUDY: This study aimed to investigate therapeutic efficacy of KSL extract
      using complete Freund's adjuvant (CFA) induced arthritis in a rat model and the
      anti-inflammatory activity of cassane diterpenes as the main active material
      basis of this herb. MATERIALS AND METHODS: Arthritis was induced in male Wistar
      rats (200-220 g) by immunization with CFA. Dexamethasone (DXMS) and Tripterygium
      glycosides (TG) were chosen as the positive drugs. Water soluble fraction (CMW,
      1000 and 2000 mg/kg) and chloroform soluble fraction (CMC, 400 and 800 mg/kg) of
      KSL were orally administered from day 1 and continued for 21 days. Change of paw
      swelling perimeter, arthritics score, body weight growth, were observed, and the
      production of TNF-alpha, IL-1beta and IL-6 in serum were measured by enzyme
      linked immunosorbent assay (ELISA). The histological changes in the ankle joint
      were analyzed in adjuvant induced arthritis rats. Moreover, the inhibitory effect
      on mRNA expression of proinflammatory cytokine IL-1beta, IL-6 and TNF-alpha of
      fourteen cassane diterpenes obtained from CMC extract were valued using the RAW
      264.7 macrophages cell stimulated by lipopolysaccharide (LPS) assay. RESULTS: The
      chloroform soluble fraction (CMC) showed the significantly suppressed change of
      paw swelling perimeter, arthritics score and increased body weight loss. The
      overproduction of TNF-alpha, IL-1beta and IL-6 were remarkably suppressed in the
      serum. Fourteen cassane derivatives as the main constituents of CMC extract
      showed the promising activity on the expression mRNA of cytokine IL-1beta, IL-6
      and TNF-alpha produced by macrophages cells. CONCLUSIONS: In this study, the
      chloroform soluble fraction of 'KSL' (seeds of C. minax) was found to exert an
      anti-RA activity significantly in vivo for the first time, which indicted this
      fraction might be used as a powerful therapeutic agent for arthritis treatments.
      Cassane diterpenes, as the main constituents in this fraction, showed the anti
      inflammation activity through the regulation of cytokine expression, which might
      be developed as target-agents for this national herb further developing.

PMID- 30114518
TI  - The inhibitory effect of Filipendula ulmaria (L.) Maxim. on colorectal
      carcinogenesis induced in rats by methylnitrosourea.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Meadowsweet (Filipendula ulmaria (L.) Maxim.) is
      a medicinal plant with a variety of therapeutic properties, traditionally used in
      various diseases including treatment and prevention of tumors. The aim of this
      study was to present an ethnomedicinal justification that a meadowsweet decoction
      is able to inhibit colorectal carcinogenesis induced by the methylnitrosourea
      (MNU) in rats. MATERIALS AND METHODS: The chemical composition of meadowsweet
      extracts was studied by traditional methods. In animal experiments adult outbred
      female rats received four intrarectal instillations of MNU, one per week, at dose
      4 mg in 0.5 ml saline (the total dose of MNU during the 4-week exposure was 16
      mg/rat). After carcinogenic exposure one group (MNU) of rats continued to receive
      standard feed and tap water throughout life. In another group (MNU+meadowsweet),
      rats were given daily a decoction of the meadowsweet instead of drinking water
      and standard feed. RESULTS: Meadowsweet extracts showed a sufficiently high
      content of flavonoids and tannins and also some individual phenolic compounds and
      salicylic acid. In rats after administration of MNU the overall incidence of
      tumors was 91% with tumor multiplicity of 3.5. The majority of rats (86%)
      developed multiple tumors of large intestine (most often adenocarcinomas:88 from
      107; index of multiplicity - 2.0). In rats from the group MNU+meadowsweet there
      was a statistically significant decrease of the overall tumor incidence and
      multiplicity-by 1.4 and 2.9 times, respectively, and the incidence and
      multiplicity of colon tumors - by 2.0 and 2.8 times, respectively; the incidence
      and multiplicity of malignant tumors of other localizations was also reduced-by
      2.2 and 3.0 times, respectively. CONCLUSIONS: Meadowsweet extract is an effective
      inhibitor of colorectal carcinogenesis in experiment, that provides support for
      the traditional use of this plant in the oncology.

PMID- 30114519
TI  - Liver-specific metabolomics characterizes the hepatotoxicity of Dioscorea
      bulbifera rhizome in rats by integration of GC-MS and 1H-NMR.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea bulbifera rhizome (DBR), one type of
      herbal medicine, is extensively used in both Indian and Chinese system of
      traditional medicine. It has been effective in treating various diseases, such as
      sore throat, struma, and tumors. However, more and more clinical investigations
      have suggested that DBR can cause liver injury. AIM OF THE STUDY: In the present
      study, we aimed to characterize the corresponding molecular changes of liver
      dysfunction and reveal overall metabolic and physiological mechanisms of the
      subchronic toxic effect of DBR. MATERIALS AND METHODS: A liver-specific
      metabolomics approach integrating GC-MS and 1H-NMR was developed to assess the
      hepatotoxicity in rats after DBR exposure for 12 weeks. Multivariate statistical
      analysis and pattern recognition were employed to examine different metabolic
      profiles of liver in DBR-challenged rats. RESULTS: A total of 61 metabolites were
      screened as significantly altered metabolites, which were distributed in 43
      metabolic pathways. The correlation network analysis indicated that the hub
      metabolites of hepatotoxicity could be mainly linked to amino acid, lipid,
      purine, pyrimidine, bile acid, gut microflora, and energy metabolisms. Notably,
      purine, pyrimidine, and gut microflora metabolisms might be novel pathways
      participating in metabolic abnormalities in rats with DBR-triggered hepatic
      damage. CONCLUSIONS: Our results primarily showed that the liver-specific
      metabolic information provided by the different analytical platforms was
      essential for identifying more biomarkers and metabolic pathways, and our
      findings provided novel insights into understand the mechanistic complexity of
      herb-induced liver injury.

PMID- 30114520
TI  - Childhood- versus Adult-Onset Polyarteritis Nodosa Results from the French
      Vasculitis Study Group Registry.
AB  - OBJECTIVE: To investigate differences between childhood (cPAN)- and adult-onset
      polyarteritis nodosa (aPAN) patients. METHODS: cPAN patients' clinical findings
      at onset and outcomes were compared to those of aPAN patients from the French
      Vasculitis Study Group registry matched for year of enrollment and initial
      systemic versus cutaneous disease. Their information on medications, disease
      activity and damage were collected. Kaplan-Meier relapse-free survival curves and
      the log-rank test were used to analyze cPAN versus aPAN differences for
      predefined outcomes. RESULTS: Twenty-one children with systemic and 13 with
      cutaneous PAN were compared with 84 systemic- and 27 cutaneous-matched aPAN
      patients. Median follow-up exceeded 5 years for both groups. At study entry,
      mononeuritis multiplex was less frequent in systemic cPAN than systemic aPAN (P =
      0.04), and purpura and myalgias were less frequent in cutaneous cPAN than
      cutaneous aPAN (P < 0.03). During follow-up, systemic cPAN relapsed more often
      than matched systemic aPAN (P < 0.0001), while relapse rates were similar for
      cutaneous disease (P > 0.05). Mostly minor relapses, predominantly involving the
      skin, occurred in all 4 groups. At last visit, damage accrual was comparable for
      cPAN and aPAN patients, but fewer systemic cPAN patients were treatment-free (15%
      versus 42%; P = 0.03). Two (6%) cPAN and 8 (7%) aPAN patients died. CONCLUSION:
      Systemic PAN is equally severe in children and adults and carries a higher risk
      of relapse. The main cutaneous PAN features seem not to be influenced by age at
      disease onset.

PMID- 30114521
TI  - Aporocotylids from batoid and elopomorph fishes from Moreton Bay, Queensland,
      Australia, including a new genus and species of blood fluke infecting the Giant
      shovelnose ray, Glaucostegus typus (Rhinopristiformes: Glaucostegidae).
AB  - Fishes of the elasmobranch superorder Batoidea and the basal teleost superorder
      Elopomorpha were assessed for blood flukes (Digenea: Aporocotylidae) during a
      parasitological survey conducted in Moreton Bay, Queensland, Australia. A new
      blood fluke genus and species, Ogawaia glaucostegi n. gen., n. sp., is described
      from the Giant shovelnose ray, Glaucostegus typus (Anonymous [Bennett])
      (Rhinopristiformes: Glaucostegidae). Ogawaia glaucostegi differs from species of
      all other aporocotylid genera in the combination of the absence of anterior caeca
      and oral sucker, having a pronounced distal oesophageal chamber, a strongly
      coiled testis and a common genital pore. The new species most closely resembles
      Myliobaticola richardheardi Bullard & Jensen, 2008, from which it differs in
      lacking an oral sucker and in possessing a straight (rather than coiled)
      oesophagus, longer caeca in proportion to the oesophageal and total body length,
      and a much longer testis relative to body length. Ogawaia glaucostegi is just the
      eighth aporocotylid described from chondrichthyans, of which four belong to
      monotypic genera. This is the first description of a blood fluke from the order
      Rhinopristiformes, and the first of a chondrichthyan-infecting aporocotylid from
      Australian waters. Elopicola bristowi Orelis-Ribeiro & Bullard, 2017 is reported
      from Australia for the first time, from the type-host, Elops hawaiensis Regan
      (Elopiformes: Elopidae). This species is identified by morphological and
      molecular data and distinctions between our specimens and those of the original
      description are discussed.

PMID- 30114523
TI  - Biobanks: let's share specimens.

PMID- 30114522
TI  - Characterization of Plasmodium knowlesi dihydrofolate reductase-thymidylate
      synthase and sensitivity to antifolates.
AB  - Malaria caused by an infection of Plasmodium knowlesi can result in high
      parasitemia and deaths. Therefore, effective and prompt treatment is necessary to
      reduce morbidity and mortality. The study aims to characterize P. knowlesi
      dihydrofolate reductase-thymidylate synthase enzyme (PkDHFR-TS) and its
      sensitivity to antifolates. The putative Pkdhfr gene was PCR amplified from field
      isolates collected from the Southern Thailand. Molecular analysis showed 11
      polymorphisms in the dhfr domain of the bifunctional dhfr-ts gene. Of these, 1
      polymorphism was a non-synonymous substitution (R34L) that had previously been
      reported but not associated with antifolate resistance. The recombinant PkDHFR-TS
      enzyme was found to be sensitive to standard antifolates-pyrimethamine and
      cycloguanil-as well as P218, a registered candidate drug currently first in human
      clinical trial. Results suggest that antifolates class of compounds should be
      effective against P. knowlesi infection.

PMID- 30114524
TI  - Description of a 2682-bp plasmid containing qnrD1 in Proteus mirabilis isolated
      from a diseased chicken.

PMID- 30114525
TI  - Expression profile and localization of vitellogenin mRNA and protein during
      ovarian development in turbot (Scophthalmus maximus).
AB  - Egg yolk generation is a common physiological process in oviparous animals. To
      understand oogenesis and reproductive capacity, it is necessary to characterize
      vitellogenins (Vtgs), which are the precursors of major egg yolk proteins (Yps).
      Therefore, to improve our understanding of the entire process of egg yolk
      generation in female turbot (Scophthalmus maximus), we obtained full-length cDNAs
      of vtg genes, examined gene expression in the female liver and ovary, and
      analyzed Vtg synthesis in the ovary. Three distinct complete polypeptide
      sequences were identified and designated as VtgAa, VtgAb, and VtgC, which
      confirmed the multiplicity of the vtg gene in turbot and showed that it follows a
      "three vtg model". The expression of these three vtg genes in the female liver
      was far higher than that in other tissues, including the ovary. The expression of
      all three vtg genes was extremely low before vitellogenesis, and then increased
      and was maintained at a high level until the degradation stage, which was in
      accordance with changes in the concentration of estradiol-17beta (E2) and the
      gonadosomatic index. Compared with the liver, the ovary had a higher E2 level and
      lower vtg expression, suggesting that some other factors limit high vtg
      expression in the ovary of turbot. Transcripts of vtgAb and the Yps derived from
      them were both detected in oogonia and primary oocytes, which showed that these
      might possess the ability to perform autosynthesis of yolk. These findings add to
      our understanding of the reproductive physiology of Vtg synthesis in turbot.

PMID- 30114526
TI  - Phoenixin participated in regulation of food intake and growth in spotted scat,
      Scatophagus argus.
AB  - Phoenixin (Pnx) is an endogenous peptide known to be involved in reproduction and
      food intake in rats, with two active isoforms, phoenixin-14 (Pnx-14) and
      phoenixin-20 (Pnx-20). However, little is known about the functions of Pnx in
      teleost. Here, pnx was cloned and was detected in all tissues of both male and
      female in spotted scat (Scatophagus argus), including growth axis, hypothalamus,
      pituitary, and liver. Real-time PCR analysis showed that pnx in the hypothalamus
      increased significantly after 2 d and 7 d fasting, while reduced significantly
      after re-feeding (P < 0.05). When pituitary and liver fragments were cultured in
      vitro with Pnx-14 and Pnx-20 (10 nM and 100 nM) for 6 h, the expression of ghrhr
      (growth hormone-releasing hormone receptor) and gh (growth hormone) in the
      pituitary, and ghr1 (growth hormone receptor 1) in the liver increased
      significantly, except ghr2 (growth hormone receptor 2) incubated with 10 nM and
      100 nM Pnx-20 and ghr1 incubated with 10 nM Pnx-20. Similarly, the expression of
      ghrhr and gh in the pituitary, as well as ghr1 and ghr2 in the liver, increased
      significantly after injecting S. argus with Pnx-14 and Pnx-20 (10 ng/g and 100
      ng/g body weight). These results indicate that Pnx is likely to be involved in
      the regulation of food intake, and also regulates the growth of S. argus by
      increasing ghrhr and gh expression in the pituitary, ghr1 and ghr2 in the liver,
      and ghr1 directly in the liver.

PMID- 30114527
TI  - Characterization of Midkine in tongue sole (Cynoglossus semilaevis)and its role
      on the germ layer genesis in zebrafish (Danio rerio).
AB  - Midkine (Mdk) is a cytokine involved in controlling tissue repair and new tissue
      development, and regulating inflammation involved in several signaling pathway,
      such as the mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3
      kinase (PI3K)/AKT pathways. But the role of Mdk in the development of Cynoglossus
      semilaevis is poorly understood. In this study, the Midkine of C. semilaevis
      (CsMdk) was cloned, and its spatiotemporal expression pattern and structural
      characteristics were analyzed. Furthermore, the essential genes related to
      nervous system development and germ layer formation marker gene were identified
      by qRT-PCR and in situ hybridization after overexpression the CsMdk via zebrafish
      model. The result showed CsMdk was mainly expressed in the brain of embryo,
      especially in the diencephalon, mid-hindbrain boundary (MHB) and hindbrain. In
      adult fish, it could only be detected in brain. Overexpression of CsMdk mRNA in
      zebrafish embryos suppressed the development of forebrain, midbrain, hindbrain
      and the notochord in zebrafish and influence the development of the mesoderm. All
      results showed CsMdk played a significant role on the germ layer and nervous
      development.

PMID- 30114528
TI  - Knowledge gaps and barriers to early peanut introduction among allergists,
      pediatricians, and family physicians.

PMID- 30114529
TI  - Pharmacological preconditioning with inhaled nitric oxide (NO): Organ-specific
      differences in the lifetime of blood and tissue NO metabolites.
AB  - BACKGROUND: Endogenous nitric oxide (NO) may contribute to ischemic and
      anesthetic preconditioning while exogenous NO protects against ischemia
      reperfusion (I/R) injury in the heart and other organs. Why those beneficial
      effects observed in animal models do not always translate into clinical
      effectiveness remains unclear. To mitigate reperfusion damage a source of NO is
      required. NO inhalation is known to increase tissue NO metabolites, but little
      information exists about the lifetime of these species. We therefore sought to
      investigate the fate of major NO metabolite classes following NO inhalation in
      mice in vivo. METHODS: C57BL/6J mice were exposed to 80 ppm NO for 1 h. NO
      metabolites were measured in blood (plasma and erythrocytes) and tissues (heart,
      liver, lung, kidney and brain) immediately after NO exposure and up to 48 h
      thereafter. Concentrations of S-nitrosothiols, N-nitrosamines and NO-heme
      products as well as nitrite and nitrate were quantified by gas-phase
      chemiluminescence and ion chromatography. In separate experiments, mice breathed
      80 ppm NO for 1 h prior to cardiac I/R injury (induced by coronary arterial
      ligation for 1 h, followed by recovery). After sacrifice, the size of the
      myocardial infarction (MI) and the area at risk (AAR) were measured. RESULTS:
      After NO inhalation, elevated nitroso/nitrosyl levels returned to baseline over
      the next 24 h, with distinct multi-phasic decay profiles in each compartment. S/N
      nitroso compounds and NO-hemoglobin in blood decreased exponentially, but
      remained above baseline for up to 30min, whereas nitrate was elevated for up to
      3hrs after discontinuing NO breathing. Hepatic S/N-nitroso species concentrations
      remained steady for 30min before dropping exponentially. Nitrate only rose in
      blood, liver and kidney; nitrite tended to be lower in all organs immediately
      after NO inhalation but fluctuated considerably in concentration thereafter. NO
      inhalation before myocardial ischemia decreased the ratio of MI/AAR by 30% vs
      controls (p = 0.002); only cardiac S-nitrosothiols and NO-hemes were elevated at
      time of reperfusion onset. CONCLUSIONS: Metabolites in blood do not reflect NO
      metabolite status of any organ. Although NO is rapidly inactivated by hemoglobin
      mediated oxidation in the circulation, long-lived tissue metabolites may account
      for the myocardial preconditioning effects of inhaled NO. NO inhalation may
      afford similar protection in other organs.

PMID- 30114531
TI  - CRAC channels in dental enamel cells.
AB  - Enamel mineralization relies on Ca2+ availability provided by Ca2+ release
      activated Ca2+ (CRAC) channels. CRAC channels are modulated by the endoplasmic
      reticulum Ca2+ sensor STIM1 which gates the pore subunit of the channel known as
      ORAI1, found the in plasma membrane, to enable sustained Ca2+ influx. Mutations
      in the STIM1 and ORAI1 genes result in CRAC channelopathy, an ensemble of
      diseases including immunodeficiency, muscular hypotonia, ectodermal dysplasia
      with defects in sweat gland function and abnormal enamel mineralization similar
      to amelogenesis imperfecta (AI). In some reports, the chief medical complain has
      been the patient's dental health, highlighting the direct and important link
      between CRAC channels and enamel. The reported enamel defects are apparent in
      both the deciduous and in permanent teeth and often require extensive dental
      treatment to provide the patient with a functional dentition. Among the dental
      phenotypes observed in the patients, discoloration, increased wear, hypoplasias
      (thinning of enamel) and chipping has been reported. These findings are not
      universal in all patients. Here we review the mutations in STIM1 and ORAI1
      causing AI-like phenotype, and evaluate the enamel defects in CRAC channel
      deficient mice. We also provide a brief overview of the role of CRAC channels in
      other mineralizing systems such as dentine and bone.

PMID- 30114530
TI  - The role of nitrite in muscle function, susceptibility to contraction injury, and
      fatigability in sickle cell mice.
AB  - Sickle cell disease (SCD) patients can have limited exercise capacity and muscle
      dysfunction characterized by decreased force, atrophy, microvascular
      abnormalities, fiber distribution changes, and skeletal muscle energetics
      abnormalities. Growing evidence suggests that in SCD there is alteration in
      nitric oxide (NO) availability/signaling and that nitrate/nitrite can serve as a
      NO reservoir and enhance muscle performance. Here, we examined effects of nitrite
      on muscle strength, exercise capacity, and on contractile properties of fast
      (extensor digitorum longus, EDL) and slow-twitch (soleus) muscles in SCD mice.
      Compared to controls, homozygotes (sickling) had decreased grip strength,
      impaired wheel running performance, and decreased muscle mass of fast-twitch, but
      not slow-twitch muscle. Nitrite treatment yielded increases in nitrite plasma
      levels in controls, heterozygotes, and homozygotes but decreases in muscle
      nitrite levels in heterozygotes and homozygotes. Regardless of genotype, nitrite
      yielded increases in grip strength, which were coupled with increases in specific
      force in EDL, but not in soleus muscle. Further, nitrite increased EDL, but not
      soleus, fatigability in all genotypes. Conversely, in controls, nitrite
      decreased, whereas in homozygotes, it increased EDL susceptibility to contraction
      induced injury. Interestingly, nitrite yielded no changes in distances ran on the
      running wheel. These differential effects of nitrite in fast- and slow-twitch
      muscles suggest that its ergogenic effects would be observed in high
      intensity/short exercises as found with grip force increases but no changes on
      wheel running distances. Further, the differential effects of nitrite in
      homozygotes and control animals suggests that sickling mice, which have altered
      NO availability/signaling, handle nitrite differently than do control animals.

PMID- 30114532
TI  - Smooth muscle gap-junctions allow propagation of intercellular Ca2+ waves and
      vasoconstriction due to Ca2+ based action potentials in rat mesenteric resistance
      arteries.
AB  - The role of vascular gap junctions in the conduction of intercellular Ca2+ and
      vasoconstriction along small resistance arteries is not entirely understood. Some
      depolarizing agents trigger conducted vasoconstriction while others only evoke a
      local depolarization. Here we use a novel technique to investigate the temporal
      and spatial relationship between intercellular Ca2+ signals generated by smooth
      muscle action potentials (APs) and vasoconstriction in mesenteric resistance
      arteries (MA). Pulses of exogenous KCl to depolarize the downstream end (T1) of a
      3 mm long artery increased intracellular Ca2+ associated with vasoconstriction.
      The spatial spread and amplitude of both depended on the duration of the pulse,
      with only a restricted non-conducting vasoconstriction to a 1 s pulse. While
      blocking smooth muscle cell (SMC) K+ channels with TEA and activating L-type
      voltage-gated Ca2+ channels (VGCCs) with BayK 8644 spread was dramatically
      facilitated, so the 1 s pulse evoked intercellular Ca2+ waves and
      vasoconstriction that spread along an entire artery segment 3000 MUm long. Ca2+
      waves spread as nifedipine-sensitive Ca2+ spikes due to SMC action potentials,
      and evoked vasoconstriction. Both intercellular Ca2+ and vasoconstriction spread
      at circa 3 mm s-1 and were independent of the endothelium. The spread but not the
      generation of Ca2+ spikes was reversibly blocked by the gap junction inhibitor
      18beta-GA. Thus, smooth muscle gap junctions enable depolarization to spread
      along resistance arteries, and once regenerative Ca2+-based APs occur, spread
      along the entire length of an artery followed by widespread vasoconstriction.

PMID- 30114533
TI  - A Novel Competing Risk Analysis Model to Determine the Role of Cervical Lordosis
      in Bony and Ligamentous Injuries.
AB  - OBJECTIVE: To determine role of lordosis in cervical spine injuries using a novel
      competing risk analysis model. METHODS: The first subgroup of published
      experiments (n = 20) subjected upright human cadaver head-neck specimens to
      impact loading. The natural lordosis was removed. The second (n = 21) and third
      (n = 10) subgroups of published tests subjected inverted specimens to head impact
      loading. Lordosis was preserved in these 2 subgroups. Using axial force and age
      as variables, competing risks analysis techniques were used to determine the role
      of lordosis in the risk of bone-only, ligament-only, and bone and ligament
      injuries. RESULTS: Bony injuries were focused more at 1 level to a straightened
      spine, and ligament injuries were spread around multiple levels. Age was not a
      significant (P < 0.05) covariate. A straightened spine had 3.23 times higher risk
      of bony injuries than a lordotic spine. The spine with maintained lordosis had
      1.14 times higher risk of ligament injuries, and 2.67 times higher risk of bone
      and ligament injuries than a spine without lordosis (i.e., preflexed column).
      CONCLUSIONS: Increased risk of bony injuries in a preflexed spine and ligament
      injuries in a lordotic spine may have implications for military personnel, as
      continuous use of helmets in the line of duty affects the natural curvature;
      astronauts, as curvatures are less lordotic after missions; and civilian patients
      with spondylotic myelopathy who use head protective devices, as curvatures may
      change over time in addition to the natural aging process.

PMID- 30114534
TI  - Predominance of Spinal Metastases Involving the Posterior Vertebral Body.
AB  - BACKGROUND: Spinal metastases pose significant morbidity. For many histologies,
      the spine is a frequent site for bone metastases. This predilection is not fully
      understood, and there are conflicting reports regarding the distribution within
      the vertebral body itself. Knowing this distribution will give clues as to the
      underlying biologic reason for this increased incidence in the spine and lead to
      a better understanding of tumor dispersion and growth. METHODS: We
      retrospectively examined magnetic resonance imaging scans of patients undergoing
      radiation to the spine from 2015 to 2017 for spinal metastases. The anatomical
      distribution of lesions was categorized. Lesions were sorted along the sagittal
      plane into 5 groups: anterior only, anterior + middle, middle only, posterior +
      middle, and posterior only. Lesions that covered all groups were discarded. chi2
      and post-hoc analyses were used for statistical analyses. RESULTS: Three hundred
      metastatic lesions were examined in 89 patients; 203 lesions were used for
      analysis. Sixty-five percent of all lesions were found in posterior only and
      posterior + middle aspects of the vertebral body (P < 0.0001). This localization
      was significant regardless of histology: lung (67%, P < 0.0001), kidney (66%, P <
      0.0001), sarcoma (67%, P < 0.0001), prostate (63%, P = 0.01), and breast (63%, P
      = 0.01). This was consistent across thoracic (n = 96) and lumbar (n = 63) regions
      (72% and 64%, respectively, P < 0.0001). CONCLUSIONS: Metastatic lesions of the
      thoracolumbar spine have a greater propensity to localize to the posterior aspect
      of the vertebral body. These data support the hypothesis that there may be
      differences within the vertebral body leading to differential tumor dispersion
      and growth.

PMID- 30114535
TI  - Demonstration of Infectious Transgression Through the Skull Base Occurring 9
      Years After Pituitary Adenoma Resection.
AB  - BACKGROUND: Sellar infections represent less than 1% of all sellar lesions and
      can be life-threatening. These infections occur de novo in up to 70% of patients
      or can less commonly develop after surgical treatment of another primary lesion,
      such as a pituitary adenoma. CASE DESCRIPTION: We report a unique case of a 27
      year-old woman with a recurrent pituitary adenoma treated with 2 previous
      transsphenoidal resections. She ultimately presented with hypopituitarism,
      followed by headaches, malaise, chills, and visual-field and acuity deficits 9
      years after her second transsphenoidal resection. During the second operation,
      the sellar floor was reconstructed with hydroxyapatite bone cement. On the most
      recent presentation, magnetic resonance imaging of the brain and pituitary
      demonstrated a residual sellar mass accompanied by significant enhancement and T2
      hyperintensity of the infundibulum, hypothalamus, optic chiasm, and optic tracts.
      The patient was started on empiric antibiotics and steroids before frank
      purulence in the sella was discovered and removed by transsphenoidal endoscopy.
      Cultures were positive for methicillin-sensitive Staphylococcus aureus and
      Propionibacterium acnes. At her 3-month follow-up evaluation, the patient had
      complete resolution of her symptoms and radiographic findings. CONCLUSIONS: This
      case demonstrates the fact that patients with pituitary lesions who have foreign
      material used for surgical closure can present with infections many years after
      the initial intervention. Furthermore, with appropriate clinical diagnosis and
      treatment, the reactive inflammation caused by sellar infection is reversible. We
      review the literature regarding the risk factors and management strategies for
      delayed postoperative sellar infections.

PMID- 30114536
TI  - Effect of Dural Substitute and Technique on Cranioplasty Operative Metrics: A
      Systematic Literature Review.
AB  - BACKGROUND: Cranioplasty after decompressive craniectomy can be associated with
      significant morbidity. Dural substitutes during the initial decompression could
      improve outcomes. METHODS: We performed a systematic literature review of online
      peer-reviewed databases to determine the effect of dural substitutes during
      decompressive craniectomy on operative metrics and outcomes after subsequent
      cranioplasty. RESULTS: Nine studies from 2006 to 2018 had reported the results
      from 922 patients undergoing autologous cranioplasty. Seven types of dural
      substitute were described, including biologic and synthetic materials. Compared
      with no graft, the use of dural substitutes was associated with significantly
      decreased operative times and surgical blood loss during subsequent cranioplasty.
      One study evaluated dual-layer substitutes and documented superior results
      compared with single layer. The most commonly reported complications were
      infection and cerebrospinal fluid leak; however, a significant reduction in
      complications was seen in only 1 study. CONCLUSIONS: The use of dural substitutes
      was associated with superior operative metrics, complication rates, and long-term
      outcomes.

PMID- 30114537
TI  - Analysis of Peripheral Nerve Schwannoma Pseudocapsule.
AB  - BACKGROUND: Using proper surgical technique, schwannomas can be resected safely,
      with a low recurrence rate and high likelihood of improvement in symptomatology.
      There are multiple peritumoral tissue layers, and finding the correct plane is
      critical to safe tumor enucleation. The contents of the pseudocapsule tissue
      surrounding a schwannoma are not well described, and the consequences of
      resecting or leaving pseudocapsules are unknown. METHODS: An institutional
      database was searched for any pathology reports that contained both of the words
      "schwannoma" and "capsule." Charts and histopathologic specimens were reviewed to
      determine the contents of various tissue layers and determine if there was any
      correlation between pseudocapsular contents and clinical outcomes. RESULTS: A
      pseudocapsule was separately sent for pathology in 36 patients during schwannoma
      resection. Ten pseudocapsule specimens contained microscopic foci of tumor. In a
      separate 6 patients, there was evidence of nerve fascicles. There were no
      correlations between the tumor or nerve in the pseudocapsule and postoperative
      neurologic deficits. After an average follow-up time of 3.1 years, no patients
      developed a recurrence either clinically or on follow-up imaging (imaging
      available in 52.7%). Histopathologically, the pseudocapsule was made of dense
      hypocellular collagen and occasionally contained arteries, veins, and nerve
      fascicles. CONCLUSIONS: The pseudocapsule surrounding a schwannoma occasionally
      contained nerve tissue and blood vessels. While a microscopic focus of tumor was
      often found in this tissue layer, recurrence is exceedingly rare and did not
      occur in this case series. The risk of undue pseudocapsule dissection likely
      outweighs any negligible benefit from microscopic cytoreduction.

PMID- 30114538
TI  - Spontaneous Regression of a True Intracanalicular Fusiform Ophthalmic Artery
      Aneurysm After Endovascular Treatment of an Associated Dural Arteriovenous
      Fistula.
AB  - BACKGROUND: Ophthalmic trunk aneurysms associated with other vascular
      malformations are extremely rare, and little is known regarding its natural
      history and options of treatment. CASE DESCRIPTION: We present the interesting
      case of a 51-year-old man who was admitted with progressive visual loss secondary
      to a concurrent fusiform ophthalmic trunk aneurysm associated with a dural
      arteriovenous fistula. He was treated with transarterial embolization of the
      fistulous point. CONCLUSIONS: A follow-up angiogram at 6 months showed complete
      obliteration of the dural arteriovenous fistula and regression of the ophthalmic
      trunk aneurysm. The literature is reviewed, and potential pathophysiologic
      mechanisms leading to this association and regression in this subgroup of
      aneurysms are discussed.

PMID- 30114539
TI  - Candida parapsilosis Infection of Ventriculoperitoneal Shunt in Adult: Case
      Report and Literature Review.
AB  - BACKGROUND: Candida parapsilosis is an incredibly rare cause of
      ventriculoperitoneal (VP) shunt infections, with only 1 adult case reported in
      the literature to date. CASE DESCRIPTION: We describe the case of a 45-year-old
      man admitted for a traumatic fall and subsequently treated with VP shunt
      placement for obstructive hydrocephalus secondary to a cerebellar contusion and
      intraventricular hemorrhage. Eight months following VP shunt placement, the
      patient presented with a 2-month history of clear fluid leakage through a
      dehiscent surgical abdominal wound overlying the distal VP shunt. Cerebrospinal
      fluid cultures were obtained and grew C. parapsilosis. The patient subsequently
      underwent VP shunt externalization and began antifungal treatment with
      intravenous liposomal amphotericin B. Cerebrospinal fluid studies continued to
      redemonstrate C. parapsilosis infection, for which VP shunt removal and external
      ventricular drain placement was performed. Three days into treatment with
      amphotericin B, he endured significant nephrotoxicity necessitating a switch to
      oral fluconazole. Following 3 weeks of oral fluconazole treatment with negative
      serial cerebrospinal fluid cultures, the patient underwent external ventricular
      drain removal and VP shunt insertion. Following the procedure and 22 total days
      of oral fluconazole treatment, our patient recovered well and was discharged to a
      rehabilitation facility in stable condition. CONCLUSIONS: In our report, we
      describe the clinical course of our patient and offer a review and analysis of
      the most up-to-date literature concerning C. parapsilosis shunt infections, as
      well as treatment guidelines for central nervous system candidiasis.

PMID- 30114540
TI  - Risk of Pseudoarthrosis After Spinal Fusion: Analysis From the Healthcare Cost
      and Utilization Project.
AB  - BACKGROUND: Pseudoarthrosis after spinal fusion is an important cause of pain,
      neurologic decline, and reoperation. METHODS: The Healthcare Cost and Utilization
      Project State Inpatient Databases were queried in New York, California, Florida,
      and Washington for adult patients who had undergone new spinal fusion from 2009
      to 2011. In accordance with the Healthcare Cost and Utilization Project methods
      series and analysis guidelines, generalized linear mixed effects models were used
      to estimate the odds of experiencing postoperative pseudoarthrosis as a function
      of multivariable patient characteristics, comorbidities, and surgical approach.
      RESULTS: Of the 107,420 patients who had undergone cervical fusion, 1295 (1.2%)
      developed pseudoarthrosis requiring reoperation. On multivariable analysis, the
      risk factors included posterior (odds ratio [OR], 4.47; 95% confidence interval
      [CI], 3.92-5.10) and combined (OR, 1.77; 95% CI, 1.33-2.36) approaches, fusion of
      >=9 vertebrae (OR, 2.54; 95% CI, 1.38-4.68), smoking (OR, 1.19; 95% CI, 1.05
      1.34), and long-term steroid use (OR, 1.89; 95% CI, 1.18-3.00). Of the 148,081
      patients who underwent thoracic or lumbar fusion, 2665 (1.8%) developed
      pseudoarthrosis. Posterior (OR, 0.58; 95% CI, 0.51-0.56) and combined (OR, 0.46;
      95% CI, 0.40-0.54) approaches resulted in reduced rates. Fusion of 4-8 vertebrae
      (OR, 1.52; 95% CI, 1.39-1.67), >=9 vertebrae (OR, 1.87; 95% CI, 1.49-2.34),
      hypertension (OR, 1.18; 95% CI, 1.09-1.28), sleep apnea (OR, 1.48; 95% CI, 1.26
      1.72), smoking (OR, 1.22; 95% CI, 1.12-1.33), and long-term steroid use (OR,
      1.53, 95% CI, 1.08-2.18) resulted in increased rates. CONCLUSIONS: These findings
      strongly associate several diagnoses with the development of pseudoarthrosis.
      However, further prospective studies are warranted to establish causation.

PMID- 30114541
TI  - Unilateral Supraorbital Approach to Clip Bilateral Posterior Communicating Artery
      Aneurysms: 2-Dimensional Operative Video.
AB  - This video (Video 1) demonstrates bilateral posterior communicating artery (PCoA)
      aneurysms that were treated through a unilateral supraorbital approach. A 53-year
      old woman presented with a Hunt-Hess grade I subarachnoid hemorrhage. Computed
      tomography scan showed subarachnoid hemorrhage in the left sylvian fissure and
      basal cistern. Angiography demonstrated bilateral aneurysms of the PCoA.
      Considering posteromedial projection of the contralateral aneurysm, a unilateral
      approach from the side of the ruptured aneurysm was chosen to clip bilateral
      aneurysms. The patient was positioned supine, and the aneurysm was exposed via
      the left lateral supraorbital approach. We firstly opened the chiasmatic cistern
      and left carotid cistern, followed by the proximal part of the sylvian fissure.
      Coagulation of the dura covering the anterior clinoid process and partial
      clinoidectomy were performed to expose the proximal aneurysm neck. The anterior
      choroid artery was separated from the distal aneurysm neck. The aneurysm was
      clipped with a simple straight clip. The interoptic space and contralateral optic
      carotid space were further dissected to expose the contralateral carotid artery,
      PCoA, anterior choroid artery, and neck of the aneurysm. A fenestrated clip was
      used to occlude the aneurysm with preservation of these critical vessels. The
      patient recovered well without any complications. Postoperative angiography
      confirmed complete obliteration of these 2 aneurysms. For selected bilateral PCoA
      aneurysms with non-low-lying and posteromedial projection of the contralateral
      aneurysm, surgical clipping of all aneurysms via a unilateral approach is a
      feasible alternative.

PMID- 30114542
TI  - Modified Posterior Short-Segment Pedicle Screw Instrumentation for Lumbar Burst
      Fractures with Incomplete Neurological Deficit.
AB  - PURPOSE: We have introduced a method of modified posterior short-segment pedicle
      screw fixation and evaluated its clinical effects in treating lumbar burst
      fractures with incomplete neurological deficits. METHODS: The data from 22
      patients with lumbar burst fracture and incomplete neurological deficits who had
      undergone modified posterior short-segment instrumentation with Schanz screw
      fixation from January 2012 to February 2018 in our clinic were evaluated in the
      present retrospective study. All Schanz screws were implanted in an oblique
      downward direction into the vertebrae above and below the injured vertebra
      (insertion depth, 90%-100%). The implants were removed ~1 year after surgery.
      Neurological function, back pain, anterior and posterior body height ratio,
      kyphosis angle, percentage of canal compromise, fracture severity, and treatment
      related complications were evaluated. RESULTS: Technical success was achieved in
      all 22 patients. No infection, instrument loosening or failure, or breakage was
      observed. Statistically significant improvements with regard to the anterior body
      height (P < 0.05) and posterior body height (P < 0.05) ratios, kyphosis angle,
      and percentage of canal compromise (P < 0.05) were observed at 1 week
      postoperatively or the final follow-up visit. No correction loss had occurred at
      the final follow-up examination. Postoperatively, all patients with neurological
      deficits had functional improvement equivalent to >=1 grade on the American
      Spinal Injury Association impairment scale and fracture union. Back pain was
      greatly improved postoperatively. CONCLUSIONS: Short-segment Schanz screw
      fixation implanted in an oblique downward direction seems to be a promising
      method for lumbar burst fractures with incomplete neurological deficits because
      it provided good clinical and radiographic outcomes.

PMID- 30114543
TI  - The CRISPR-Cas9 Genome Editing System: Not as Precise as Previously Believed.

PMID- 30114544
TI  - Frontal Tumefactive Demyelinating Lesion Mimicking Glioblastoma Differentiated by
      Methionine Positron Emission Tomography.
AB  - BACKGROUND: Tumefactive demyelinating lesion (TDL) is often reported as a rare
      variation of multiple sclerosis (MS). TDL is difficult to diagnose solely by
      magnetic resonance imaging (MRI) in patients with no history of MS. This is
      because the lesion often shows ring enhancement with perifocal brain edema on
      gadolinium MRI, thus mimicking glioblastoma multiforme (GBM). CASE DESCRIPTION: A
      54-year-old healthy woman complained of headache 1 month before admission. She
      developed a decline in cognitive function, decreased attention, and executive
      function disorder 10 days before admission. Gadolinium magnetic resonance imaging
      showed a ring-shaped enhancement accompanied by massive brain edema in the left
      frontal lobe. This suggested GBM, but methionine positron emission tomography
      (MET PET), surprisingly, showed no uptake with a tumor-to-normal brain ratio of
      1.18. Accordingly, we eliminated GBM and suspected brain abscess because
      diffusion-weighted images showed high signal intensity in the lesion. Although we
      performed drainage, we could not demonstrate the presence of pus. Pathologic
      analysis of a specimen obtained by needle biopsy revealed broad necrosis and a
      small number of inflammatory cells. We therefore prescribed steroid therapy, by
      which symptoms gradually improved. No relapse occurred for 2 years. We finally
      diagnosed the patient as having TDL. CONCLUSIONS: MET PET is considered a
      possible diagnostic modality for demyelinating disease as it can appropriately
      reflect pathologic findings. MET PET will facilitate decision making regarding
      surgery in patients with TDL.

PMID- 30114545
TI  - Comparison of cow-side diagnostic techniques for subclinical endometritis in
      dairy cows.
AB  - A limited number of cow-side diagnostic techniques exist for the diagnosis of
      subclinical endometritis (SCE) in dairy cattle. The objectives of this study were
      to compare results of endometrial cytology from samples collected by cytobrush
      (CB) and low-volume lavage (LVL) and to assess leukocyte esterase (LE) test
      strips and Brix refractometry as surrogate cow-side tests for SCE. Two samples
      were consecutively collected from 248 Holstein cows between 29 and 35 days
      postpartum, using CB and LVL techniques. Each sample was analyzed using cytology
      with a cut-point of >=5% polymorphonuclear (PMN) cells, LE strips using cut
      points of >=1 and >= 2, and a Brix refractometer. Each diagnostic technique was
      compared intra-sample using the respective cytology as a gold standard and inter
      sample using CB samples as the referent. The concordance correlation coefficient
      (CCC, rhoc) for PMN% between CB and LVL was rhoc = 0.59 [95% confidence interval
      (CI): 0.50 to 0.67] and the Kappa (kappa) for agreement was kappa = 0.35
      [sensitivity (Se) = 0.88, specificity (Sp) = 0.45]. The optimal cut-point of LE
      >= 2 resulted in moderate agreement between CB and LVL samples, kappa = 0.56 (Se
      = 0.89, Sp = 0.65). Agreement between LE and cytology using CB (kappa = 0.49; Se
      = 0.89, Sp = 0.57) and LVL (kappa = 0.44; Se = 0.77, Sp = 0.67) were similar. The
      correlation between Brix values from CB and LVL was rhoc = 0.12 (CI -0.01 to
      0.26). The correlation between CB cytology and Brix was rhoc = 0.33 (CI 0.20 to
      0.45) but rhoc = -0.07 (CI -0.21 to 0.06) between LVL cytology and Brix. While LE
      strips with a cut-point of LE >= 2 had moderate agreement with cytology, Brix
      refractometry had poor performance for the diagnosis of SCE. Samples taken by CB
      and LVL produced comparable cow-side diagnostic results and either is a viable
      method for the diagnosis of SCE.

PMID- 30114546
TI  - Is it possible to predict falls in older adults using gait kinematics?
AB  - BACKGROUND: Gait kinematic parameters have been reported as an important clinical
      tool to assess the risk of falls in older adults. However, the ability of these
      parameters to predict falls in the older population is still unclear. OBJECTIVE:
      To identify the ability that gait kinematic parameters present to predict fall in
      older adults. METHODS: Data from 102 older adults, who live in a community
      setting, were considered for this study. For data collection, older subjects had
      to walk on a 14 meter-walkway in their preferred gait speed. The incidence of
      falls was recorded at baseline together with gait kinematics and then every three
      months during the period of the study. The ability of gait kinematic parameters
      to predict falls was tested using the ROC curve. RESULTS: Stance time
      variability, swing time, and stride length presented a sensitivity to predict
      falls in older adults higher than 70%. CONCLUSION: Gait kinematic parameters,
      such as stance variability, swing time, and stride length may predict future
      falls in older adults.

PMID- 30114547
TI  - SSVEP recognition by modeling brain activity using system identification based on
      Box-Jenkins model.
AB  - The steady-state visual evoked potential (SSVEP) based brain-computer interface
      (BCI) has received increasing attention in recent years. The present study
      proposes a new method for recognition based on system identification. The method
      relies on modeling the electroencephalogram (EEG) signals using the Box-Jenkins
      model. In this approach, the recorded EEG signal is considered as a combination
      of an SSVEP signal evoked by periodic visual stimulation and a background EEG
      signal whose components are modeled by a moving average (MA) process and an auto
      regressive moving average (ARMA) process, respectively. Then, the target
      frequency is determined by comparing the modeled SSVEP signals for all
      stimulation frequencies. The experimental results of the proposed method for
      recorded EEG signals from five subjects (each subject with four stimulation
      frequencies) demonstrated a significant improvement in the accuracy of the SSVEP
      recognition in contrast to canonical correlation analysis, least absolute
      shrinkage and selection operator, and multivariate linear regression methods. The
      proposed method exhibits enhanced accuracy especially for short data length and a
      small number of channels. This superiority suggests that the proposed method is
      an appropriate choice for the implementation of real-time SSVEP based BCI
      systems.

PMID- 30114548
TI  - Production of plant metabolites with applications in the food industry using
      engineered microorganisms.
AB  - Secondary plant metabolites are extensively used in today's food industries, for
      example, as coloring-agents, flavouring-agents or texturizing agents. In
      particular, metabolites with antioxidative properties find applications as
      preservatives or anti-browning agents. Today, extraction from plant material
      represents the major source of these metabolites, but progress in the field of
      metabolic engineering also enabled the microbial production of these valuable
      compounds as a more economic and ecological alternative. This review article
      presents the current state of metabolic engineering of microorganisms for
      production of plant metabolites with applications in the food industries. We
      focus on compounds, which are already used in food applications, discuss current
      limitations of microbial plant metabolite production, and outline strategies on
      how these challenges can be addressed in the future.

PMID- 30114549
TI  - Deep convolutional neural network-based segmentation and classification of
      difficult to define metastatic spinal lesions in 3D CT data.
AB  - This paper aims to address the segmentation and classification of lytic and
      sclerotic metastatic lesions that are difficult to define by using spinal 3D
      Computed Tomography (CT) images obtained from highly pathologically affected
      cases. As the lesions are ill-defined and consequently it is difficult to find
      relevant image features that would enable detection and classification of lesions
      by classical methods of texture and shape analysis, the problem is solved by
      automatic feature extraction provided by a deep Convolutional Neural Network
      (CNN). Our main contributions are: (i) individual CNN architecture, and pre
      processing steps that are dependent on a patient data and a scan protocol - it
      enables work with different types of CT scans; (ii) medial axis transform (MAT)
      post-processing for shape simplification of segmented lesion candidates with
      Random Forest (RF) based meta-analysis; and (iii) usability of the proposed
      method on whole-spine CTs (cervical, thoracic, lumbar), which is not treated in
      other published methods (they work with thoracolumbar segments of spine only).
      Our proposed method has been tested on our own dataset annotated by two mutually
      independent radiologists and has been compared to other published methods. This
      work is part of the ongoing complex project dealing with spine analysis and spine
      lesion longitudinal studies.

PMID- 30114550
TI  - Quantification of the detailed cardiac left ventricular trabecular morphogenesis
      in the mouse embryo.
AB  - During embryogenesis, a mammalian heart develops from a simple tubular shape into
      a complex 4-chamber organ, going through four distinct phases: early primitive
      tubular heart, emergence of trabeculations, trabecular remodeling and development
      of the compact myocardium. In this paper we propose a framework for standardized
      and subject-independent 3D regional myocardial complexity analysis, applied to
      analysis of the development of the mouse left ventricle. We propose a
      standardized subdivision of the myocardium into 3D overlapping regions (in our
      case 361) and a novel visualization of myocardial complexity, whereupon we: 1)
      extend the fractal dimension, commonly applied to image slices, to 3D and 2) use
      volume occupied by the trabeculations in each region together with their surface
      area, in order to quantify myocardial complexity. The latter provides an
      intuitive characterization of the complexity, given that compact myocardium will
      tend to occupy a larger volume with little surface area while high surface area
      with low volume will correspond to highly trabeculated areas. Using 50 mouse
      embryo images at 5 different gestational ages (10 subjects per gestational age),
      we demonstrate how the proposed representation and complexity measures describe
      the development of LV myocardial complexity. The mouse embryo data was acquired
      using high resolution episcopic microscopy. The complexity analysis per region
      was carried out using: 3D fractal dimension, myocardial volume, myocardial
      surface area and ratio between the two. The analysis of gestational ages was
      performed on embryos of 14.5, 15.5, 16.5, 17.5 and 18.5 embryonic days, and
      demonstrated that the regional complexity of the trabeculations increases
      longitudinally from the base to the apex, with a maximum around the middle. The
      overall complexity decreases with gestational age, being most complex at 14.5.
      Circumferentially, at ages 14.5, 15.5 and 16.5, the trabeculations show similar
      complexity everywhere except for the anteroseptal and inferolateral area of the
      wall, where it is smaller. At 17.5 days, the regions of high complexity become
      more localized towards the inferoseptal and anterolateral parts of the wall. At
      18.5 days, the high complexity area exhibits further localization at the
      inferoseptal and anterior part of the wall.

PMID- 30114551
TI  - Three new case reports of Arteriovenous malformation-related Amyotrophic Lateral
      Sclerosis.
AB  - Despite recent advances in genetics, in most cases of Amyotrophic Lateral
      Sclerosis (ALS) no etiological factor can be identified. Cerebral Arteriovenous
      Malformations (AVMs) have been associated with ALS development in a few studies,
      but the nature of this connection is unclear. We report here 3 additional cases
      of young adults, who had undergone repeated embolizations for complex AVMs, and
      who then developed, after many years, ALS symptoms and signs. In two of these
      cases Vascular Endothelial Growth Factor (VEGF) levels were found to be extremely
      high, in contrast to previous reports. Our 3 cases, together with the previously
      reported ones, suggest that a subgroup of patients with AVMs, with a particular
      profile of a complex nidus with repeated embolization procedures, are at
      increased risk of developing ALS. The reason for this association is unclear, but
      may relate to dysregulation of secreted vascular factors, as suggested by our
      VEGF results, or more broadly to the neurovascular hypothesis of ALS.
      Alternatively, a transneuronal type of neurodegeneration may be involved.

PMID- 30114552
TI  - Development of inhibition and switching: A longitudinal study of the maturation
      of interference suppression and reversal processes during childhood.
AB  - Inhibition and switching are executive functions (EFs) that have different
      developmental trajectories across childhood. The development of specific
      processes unique to each EF may contribute to these trajectories. Interference
      suppression and reversal were examined in a large sample of children aged 7 and 9
      years (n = 120) and followed-up after two-years to investigate developmental
      trajectories of inhibition and switching. The N2 and P3b components provided
      neural correlates of conflict monitoring and attentional processing of conflict
      involved in interference suppression and reversal. Interference suppression
      improved over time, however, switching performance did not significantly change
      between 7 and 11 years. Improvements in correct RT with age and time indicated
      increased efficiency of stimulus evaluation, response preparation and execution.
      N2 amplitude decreased with both age and time, indicating less reliance on
      conflict monitoring to signal cognitive control to manage stimulus and response
      conflict. P3b amplitude modulations indicated that different amounts of attention
      were allocated to updating mental representations of interference suppression and
      reversal task features. These data indicated different developmental trajectories
      of specific processes unique to inhibition and switching across the childhood
      period of 7-11 years, providing further empirical evidence that 7-11 years is a
      critical period for cognitive development.

PMID- 30114553
TI  - A preliminary study on potential association between psychopathological status
      and rhythmic masticatory muscle activity of young patients with sleep bruxism in
      Tianjin China.
AB  - OBJECTIVES: The aim of this cross-sectional study was to assess the psychological
      status of patients with bruxism and to explore the potential relationship between
      psychological status and rhythmic masticatory muscle activity (RMMA), since the
      basic manifestation of sleep bruxism is RMMA. METHODS: Twenty-five patients (nine
      males, 16 females, and mean age 27.84 +/- 5.60) who self-reported having SB and
      25 normal subjects were randomly recruited. Fifty subjects filled out the Symptom
      Checklist-90 (SCL-90) to assess their psychopathological status. SB was diagnosed
      by polysomnography (PSG), and RMMA was recorded based on the results of PSG.
      RESULTS: In this study we detected 15.89 +/- 4.23 RMMA episodes per hour in
      normal subjects, whereas 41.23 +/- 16.78 RMMA episodes per hour were recorded in
      patients with SB, which was nearly three times of the former group with
      statistical significance (P = 0.001). Paired t-test revealed significant
      differences between SB patients and normal subjects in any of the SCL-90
      subscales (P = 0.001). Regarding total psychopathological scores, 10 of the 25 SB
      patients endorsed scores higher than 160, and the positive rate was 40%. In
      addition, obsessive-compulsive behavior, interpersonal sensitivity, depression,
      anxiety, paranoid ideation and psychoticism were all statistically associated
      with RMMA (P < 0.05). CONCLUSION: Within the limitations of the study, we found
      that patients with sleep bruxism tend to have poor psychological status, and
      obsessive-compulsive behavior, interpersonal sensitivity, depression, anxiety,
      paranoid ideation and psychoticism are related to onset of SB.

PMID- 30114554
TI  - Association of metformin use with vitamin B12 deficiency in the institutionalized
      elderly.
AB  - Elderly people living in long term care institutions are particularly at risk of
      vitamin B12 deficiency. The prevalence of vitamin B12 deficiency was 34.9% among
      the 1996 institutionalized elderly residents in our previous study. The present
      retrospective study evaluated the association of metformin use with vitamin B12
      deficiency in the same group of patients. Of 1996 patients, 507 (25.4%) had
      diabetes, of which 188 received metformin treatment. The prevalence of vitamin
      B12 deficiency in diabetic patients taking metformin was 53.2% compared with 31%
      (P < 0.001) of diabetic patients not taking metformin and 33.3% (P < 0.001) of
      those without diabetes. Among the vitamin B12 deficient patients, diabetic
      patients taking metformin had lower serum vitamin B12 concentration (97 pmol/L)
      than the diabetic patients not taking metformin (113 pmol/L, P < 0.001) and those
      without diabetes (111 pmol/L, P < 0.001). Subanalysis of 174 metformin users
      found that dose and duration of metformin use were significantly associated with
      vitamin B12 deficiency. Adjusted odds ratio for those taking metformin >=1500 mg
      /day was 2.72 (95% CI 1.11-6.7, P = 0.029) compared with those using metformin
      <1000mg/day. Adjusted odds ratio for those taking metformin>4 years was 3.00 (95%
      CI 1.35-6.68, P = 0.007) compared with those taking metformin <2 years.
      Prevalence of vitamin B12 deficiency among those taking metformin >=1500 mg/day
      for >2 years was 75.9% and was more than 2 times that of patients taking
      metformin <1500 mg/day for <=2 years (35.3%). In conclusion, metformin use is
      associated with increased risk and severity of vitamin B12 deficiency in the
      institutionalized elderly residents. Patients taking metformin >=1500 mg/day for
      >2 years are particularly at risk. Testing for vitamin B12 status before and
      regularly after the start of metformin may be considered.

PMID- 30114555
TI  - Impacts of low-temperature thermal treatment on microbial detoxification of
      tetrachloroethene under continuous flow conditions.
AB  - Coupling in situ thermal treatment (ISTT) with microbial reductive dechlorination
      (MRD) has the potential to enhance contaminant degradation and reduce cleanup
      costs compared to conventional standalone remediation technologies. Impacts of
      low-temperature ISTT on Dehalococcoides mccartyi (Dhc), a relevant species in the
      anaerobic degradation of cis-1,2-dichloroethene (cis-DCE) and vinyl chloride (VC)
      to nontoxic ethene, were assessed in sand-packed columns under dynamic flow
      conditions. Dissolved tetrachloroethene (PCE; 258 +/- 46 MUM) was introduced to
      identical columns bioaugmented with the PCE-to-ethene dechlorinating consortium
      KB-1(r). Initial column temperatures represented a typical aquifer (15  degrees
      C) or a site undergoing low-temperature ISTT (35  degrees C), and were
      subsequently increased to 35 and 74  degrees C, respectively, to assess
      temperature impacts on reductive dechlorination activity. In the 15  degrees C
      column, PCE was transformed primarily to cis-DCE (159 +/- 2 MUM), which was
      further degraded to VC (164 +/- 3 MUM) and ethene (30 +/- 0 MUM) within 17 pore
      volumes (PVs) after the temperature was increased to 35  degrees C. Regardless of
      the initial column temperature, ethene constituted >50 mol% of effluent
      degradation products in both columns after 73-74 PVs at 35  degrees C, indicating
      that MRD performance was greatly improved under low-temperature ISTT conditions.
      Increasing the temperature of the column initially at 35  degrees C resulted in
      continued VC and ethene production until a temperature of approximately 43 
      degrees C was reached, at which point Dhc activity substantially decreased. The
      abundance of the vcrA reductive dehalogenase gene exceeded that of the bvcA gene
      by 1-2.5 orders of magnitude at 15  degrees C, but this relationship inversed at
      temperatures >35  degrees C, suggesting Dhc strain-specific responses to
      temperature. These findings demonstrate improved MRD performance with low
      temperature thermal treatment and emphasize potential synergistic effects at
      sites undergoing ISTT.

PMID- 30114556
TI  - Effect of sulfate radical-based oxidation pretreatments for mitigating ceramic UF
      membrane fouling caused by algal extracellular organic matter.
AB  - Algal extracellular organic matter (EOM) released from Microcystis aeruginosa can
      cause severe membrane fouling during algae-laden water treatment. To solve this
      problem, three typical sulfate radical-based advanced oxidation processes (SR
      AOPs), i.e., ferrous iron/peroxymonosulfate (Fe(II)/PMS), UV/PMS and
      UV/Fe(II)/PMS, were employed as membrane pretreatment strategies. Their
      performance on mitigating EOM fouling of a ceramic UF membrane was systematically
      investigated and compared in the present study. The results indicated that SR
      AOPs pretreatments could promote the reduction of DOC and UV254, and the removal
      performance showed an apparent regularity of UV/Fe(II)/PMS > Fe(II)/PMS > UV/PMS.
      The pretreatments were very effective for decomposing high-MW biopolymers
      (>20,000 Da) into low-MW humic substances (1000-20,000 Da), thus reducing the
      accumulation of high-MW biopolymers on membrane surface. With respect to membrane
      fouling control, Fe(II)/PMS significantly mitigated both reversible and
      irreversible membrane fouling, whereas UV/PMS only reduced reversible fouling,
      and exhibited little effect on irreversible fouling. By contrast, UV/Fe(II)/PMS
      showed the best performance for fouling reduction due to the synergistic effect
      of UV and Fe(II) for PMS activation. The dominating fouling mechanism was
      governed by both pore blockage and cake filtration, likely due to the bimodal MW
      distribution of EOM, and SR-AOPs pretreatments delayed the transition from pore
      blockage to cake filtration. In addition, SR-AOPs prior to UF membrane were also
      very effective to improve the removal of micropollutants (i.e., ATZ, SMT and p
      CNB). These results demonstrate the potential application of SR-AOPs as
      pretreatment for membrane fouling control during algae-laden water treatment.

PMID- 30114558
TI  - Association of recipient and donor hypercholesterolemia prior allogeneic stem
      cell transplantation and graft-versus-host disease.
AB  - Few authors have reported a decreased frequency of acute graft-versus-host
      disease (aGVHD) using statins, as these medications have anti-inflammatory
      effects, however, to date, the direct association between high cholesterol and
      GVHD has not been reported. The aim of his study was to investigate the
      association of recipient and donor hypercholesterolemia with the incidence of
      aGVHD. A retrospective analysis was performed identifying allogeneic
      hematopoietic stem cell transplantation (allo-HSCT) recipients and donors at the
      National Institute of Medical Sciences and Nutrition in Mexico City between May
      1999 and August 2017. The final cohort included 113 consecutive patients
      undergoing allo-HSCT and 110 donors with complete data. Acute GVHD was present in
      24% patients. A statistically significant increase in the frequency of aGVHD
      associated with hypercholesterolemia in the recipients or donors (p = 0.03 and p
      = 0.008, respectively). Hypercholesterolemia in both, donor and recipient, was
      also associated with increased aGVHD compared to either patient or donor having
      hypercholesterolemia or neither (p = 0.002). No statistical significance was
      observed for other variables. To date, this is the first study associating
      hypercholesterolemia with aGVHD. According to our results we conclude that
      hypercholesterolemia in the donor, or in both, the patient and donor, is an
      independent factor for the development of aGVHD, however, further prospective and
      larger studies are needed as our results are preliminary.

PMID- 30114557
TI  - Splice-Modulating Oligonucleotide QR-110 Restores CEP290 mRNA and Function in
      Human c.2991+1655A>G LCA10 Models.
AB  - Leber congenital amaurosis type 10 (LCA10) is a severe inherited retinal
      dystrophy associated with mutations in CEP290. The deep intronic c.2991+1655A>G
      mutation in CEP290 is the most common mutation in LCA10 individuals and
      represents an ideal target for oligonucleotide therapeutics. Here, a panel of
      antisense oligonucleotides was designed to correct the splicing defect associated
      with the mutation and screened for efficacy and safety. This identified QR-110 as
      the best-performing molecule. QR-110 restored wild-type CEP290 mRNA and protein
      expression levels in CEP290 c.2991+1655A>G homozygous and compound heterozygous
      LCA10 primary fibroblasts. Furthermore, in homozygous three-dimensional iPSC
      derived retinal organoids, QR-110 showed a dose-dependent restoration of mRNA and
      protein function, as measured by percentage and length of photoreceptor cilia,
      without off-target effects. Localization studies in wild-type mice and rabbits
      showed that QR-110 readily reached all retinal layers, with an estimated half
      life of 58 days. It was well tolerated following intravitreal injection in
      monkeys. In conclusion, the pharmacodynamic, pharmacokinetic, and safety
      properties make QR-110 a promising candidate for treating LCA10, and clinical
      development is currently ongoing.

PMID- 30114559
TI  - CC-486 (oral azacitidine) in patients with myelodysplastic syndromes with
      pretreatment thrombocytopenia.
AB  - Thrombocytopenia is among the strongest predictors of decreased survival for
      patients with myelodysplastic syndromes (MDS) across all prognostic risk groups.
      The safety and efficacy of CC-486 (oral azacitidine) was investigated in early
      phase studies; we assessed clinical outcomes among subgroups of MDS patients from
      these studies, defined by presence or lack of pretreatment thrombocytopenia (<=75
      * 109/L platelet count). Patients received CC-486 300 mg once-daily for 14 or 21
      days of repeated 28-day cycles. Overall, 81 patients with MDS, median age 72
      years, comprised the Low Platelets (n = 45) and High Platelets (n = 36) cohorts.
      Pretreatment median platelet counts were 34 * 109/L and 198 * 109/L,
      respectively. Grade 3-4 bleeding events occurred in 2 patients in the Low
      Platelets and 1 patient in the High Platelets groups; events resolved without
      sequelae. Treatment-related mortality was reported for 7 patients, 5 of whom had
      pretreatment platelet values <25 * 109/L. Overall response rates were 38% and 46%
      in the Low Platelets and High Platelets groups, respectively. Five
      thrombocytopenic patients attained complete remission and 9 attained platelet
      hematologic improvement. In both cohorts, platelet counts dropped during the
      first CC-486 treatment cycle, then increased thereafter. Extended CC-486 dosing
      was generally well tolerated and induced hematologic responses in these patients
      regardless of pretreatment thrombocytopenia.

PMID- 30114560
TI  - Secondary acute lymphoblastic leukemia, a retrospective analysis from Washington
      University and meta-analysis of published data.
AB  - Secondary acute lymphoblastic leukemia (s-ALL) is rare and poorly defined and
      data regarding outcomes post-transplant are lacking. Here, we report a detailed
      analysis of s-ALL at our Institution. Among 211 eligible patients with ALL from
      2006 to 2017, 30 (14%) were defined as s-ALL and the remaining as primary ALL (p
      ALL). s-ALL patients were older and had higher incidence of adverse risk factors.
      Overall response (OR) after induction was not different between s-ALL and p-ALL
      (79% versus 90% respectively, p = 0.106). S-ALL group had a higher risk of
      relapse (RFS) and death (RFS HR = 1.93, 95% CI 1.2-3.12, p = 0.007. OS HR: =1.95,
      95% CI 1.18-3.23, p = 0.01). In multivariate analysis, the adverse effect of s
      ALL on RFS and OS was no longer significant, however a pooled meta-analysis of
      our and published data indicated that s-ALL is an independent risk factor for
      lower OS (HR: 1.30, 95% CI: 1.11-1.52, p < 0.01). Myeloablative allogeneic
      transplantation in s-ALL was associated with lower rates of relapse and higher
      transplant related mortality without improvement in OS. These data indicate that
      s-ALL status should be considered for risk- stratification of newly diagnosed
      ALL. The optimal conditioning regimen for s-ALL patients undergoing allogeneic
      stem cell transplantation needs to be evaluated in a larger study.

PMID- 30114561
TI  - Tinzaparin for the treatment of foetal growth retardation: An open-labelled
      randomized clinical trial.
AB  - OBJECTIVE: Foetal growth retardation (FGR) is a leading cause of perinatal death
      and long-term harms at survivors. Placental infarction plays a role in FGR, yet,
      no trials have evaluated whether low molecular weight heparins increase birth
      weight in ongoing FGR pregnancies. METHODS: An open-labelled randomized trial in
      Denmark during 2011-2016, including singleton pregnant women with FGR (estimated
      foetal weight < 2.3 percentile) diagnosed before gestational weeks 32.
      Participants were randomly assigned using sealed, blinded envelopes 1:1 to
      tinzaparin (4500 IU daily until 37 gestational weeks) or no tinzaparin. The
      primary outcomes were the observed birthweight relative to the expected for
      gestational age and gender, and foetal growth rates in the two trial groups
      evaluated by an intention to treat analysis. RESULTS: We enrolled 53 women. The
      mean gestational age was 261 days in the tinzaparin group and 246 days in the no
      treatment group. The mean birth weight was 2229 g in the tinzaparin group
      compared to 1968 g in the no treatment group. However, the birth weight relative
      to the expected from gestational age and gender was only 2.5 percentage points
      higher in the tinzaparin group [-5.1 to 10.0] (p = 0.51). The foetal growth rate
      during follow-up was 124 g/week in the tinzaparin group and 119 g/week in the no
      treatment group, a difference of 5 g/week [-19 to 29] (p = 0.67). Two perinatal
      deaths both occurred in the no treatment group. CONCLUSION: We found no evidence
      of a tinzaparin effect on the foetal growth rate or the birth weight after
      adjustment for gestational age.

PMID- 30114563
TI  - Effect of storage time and temperature on the viability of E. coli O157:H7,
      Salmonella spp., Listeria innocua, Staphylococcus aureus, and Clostridium
      sporogenes vegetative cells and spores in vacuum-packed canned pasteurized milk
      cheese.
AB  - The effect of storage temperature and time on the viability of several foodborne
      bacterial pathogens inoculated into vacuum-packed canned pasteurized cow's milk
      cheese was investigated. Three popular cheese styles namely, a semi-soft white
      Monterey Jack style cheese, and two Cheddar cheeses vacuum packaged in mason jars
      were inoculated with a 3-strain cocktail of each of the following microbes at the
      mean concentrations listed: Escherichia coli O157:H7 (6.6 log CFU/g), Salmonella
      spp. (6.3 log CFU/g), Listeria innocua (6.4 log CFU/g), Staphylococcus aureus
      (3.6 log CFU/g), and Clostridium sporogenes vegetative cells (6.3 log CFU/g), and
      spores (6.0 log CFU/g). The effect of storage temperature (at 4.4, 10, and 21.1 
      degrees C) and the time (from 0 to 365 days) on the survival of the inoculated
      organisms was evaluated at different sampling times (0, 30, 60, 120,180, and 365
      days). Both storage temperature and the time had a significant effect on the
      viability of the test organisms. Increasing the storage temperature from 4.4 to
      21.1  degrees C and the storage time for up to 365 days increased pathogen
      reduction. The type of cheese also had a significant effect on the viability of
      the test organisms. At the same sampling times, the viability of E. coli O157:H7
      and Salmonella spp., were highest in Monterey Jack-style cheese followed by the
      Cheddar cheeses one to which annatto had been added (Cheddar 1) and the second, a
      white Cheddar that has an added adjunct flavor culture (Cheddar 2). Similarly,
      the type of cheese and the time-temperature conditions to which the cheese was
      exposed had a significant effect on the viability of L. innocua. Among the tested
      organisms, S. aureus was most susceptible while C. sporogenes (both vegetative
      cells and spores) were most resistant. The findings of this challenge study
      indicate that vacuum packed canned cheese is not a favorable environment for the
      growth of bacterial pathogens. Depending upon the type of canned cheese,
      appropriate storage times and temperatures are critical to ensure microbiological
      safety.

PMID- 30114562
TI  - The effect of surface poly(ethylene glycol) length on in vivo drug delivery
      behaviors of polymeric nanoparticles.
AB  - Engineering nanoparticles of reasonable surface poly(ethylene glycol) (PEG)
      length is important for designing efficient drug delivery systems. Eliminating
      the disturbance by other nanoproperties, such as size, PEG density, etc., is
      crucial for systemically investigating the impact of surface PEG length on the
      biological behavior of nanoparticles. In the present study, nanoparticles with
      different surface PEG length but similar other nanoproperties were prepared by
      using poly(ethylene glycol)-block-poly(epsilon-caprolactone) (PEG-b-PCL)
      copolymers of different molecular weights and incorporating different contents of
      PCL3500 homopolymer. The molecular weight of PEG block in PEG-PCL was between
      3400 and 8000 Da, the sizes of nanoparticles were around 100 nm, the terminal PEG
      density was controlled at 0.4 PEG/nm2 (or the frontal PEG density was controlled
      at 0.16 PEG/nm2). Using these nanoproperties well-designed nanoparticles, we
      demonstrated PEG length-dependent changes in the biological behaviors of
      nanoparticles and exhibited nonmonotonic improvements as the PEG molecular weight
      increased from 3400 to 8000 Da. Moreover, under the experimental conditions, we
      found nanoparticles with a surface PEG length of 13.8 nm (MW = 5000 Da)
      significantly decreased the absorption with serum protein and interaction with
      macrophages, which led to prolonged blood circulation time, enhanced tumor
      accumulation and improved antitumor efficacy. The present study will help to
      establish a relatively precise relationship between surface PEG length and the in
      vivo behavior of nanoparticles.

PMID- 30114564
TI  - Firm responses to targeted consumer incentives: Evidence from reference pricing
      for surgical services.
AB  - This paper examines how health care providers respond to a reference pricing
      insurance program that increases consumer cost sharing when consumers choose high
      priced surgical providers. We use geographic variation in the population covered
      by the program to estimate supply-side responses. We find limited evidence of
      market segmentation and price reductions for providers with baseline prices above
      the reference price. Finally, approximately 75% of the reduction in provider
      prices is in the form of a positive externality that benefits a population not
      subject to the program.

PMID- 30114565
TI  - Shale gas development and infant health: Evidence from Pennsylvania.
AB  - This research exploits the introduction of shale gas wells in Pennsylvania in
      response to growing controversy around the drilling method of hydraulic
      fracturing. Using detailed location data on maternal addresses and GIS
      coordinates of gas wells, this study examines singleton births to mothers
      residing close to a shale gas well from 2003 to 2010 in Pennsylvania. The
      introduction of drilling increased low birth weight and decreased term birth
      weight on average among mothers living within 2.5 km of a well compared to
      mothers living within 2.5 km of a permitted well. Adverse effects were also
      detected using measures such as small for gestational age and APGAR scores, while
      no effects on gestation periods were found. In the intensive margin, an
      additional well is associated with a 7 percent increase in low birth weight, a 5
      g reduction in term birth weight and a 3 percent increase in premature birth.
      These results are robust to other measures of infant health, many changes in
      specification and falsification tests. These findings suggest that shale gas
      development poses significant risks to human health.

PMID- 30114566
TI  - Gibberellic acid affects the functioning of the flower abscission zone in Lupinus
      luteus via cooperation with the ethylene precursor independently of abscisic
      acid.
AB  - The abscission of plant organs is a phytohormone-controlled process. Our study
      provides new insight into the involvement of gibberellic acid (GA3) in the
      functioning of the flower abscission zone (AZ) in yellow lupine (Lupinus luteus
      L.). Physiological studies demonstrated that GA3 stimulated flower abortion.
      Additionally, this phytohormone was abundantly presented in the AZ cells of
      naturally abscised flowers, especially in vascular bundles. Interesting
      interactions among GA3 and other modulators of flower separation were also
      investigated. GA3 accumulated after treatment with the ethylene (ET) precursor 1
      aminocyclopropane-1-carboxylic acid (ACC). Abscisic acid (ABA) treatment did not
      cause such an effect. Furthermore, the expression of the newly identified
      LlGA20ox1 and LlGA2ox1 genes encoding 2-oxoglutarate-dependent dioxygenases
      fluctuated after ACC or ABA treatment which confirmed the existence of regulatory
      crosstalk. GA3 appears to cooperate with the ET precursor in the regulation of AZ
      function in L. luteus flowers; however, the presented mechanism is ABA
      independent.

PMID- 30114567
TI  - Source contributions to water-soluble organic carbon and water-insoluble organic
      carbon in PM2.5 during Spring Festival, heating and non-heating seasons.
AB  - To investigate the influences of anthropogenic activities on carbon aerosols,
      especially on water-soluble organic carbon (WSOC), PM2.5 samples were collected
      at an urban site in a northern city of China during Spring Festival (SF), heating
      season (HS), and non-heating season (NHS). Carbonaceous species and ions (Ca2+,
      SO42-, NO3-, etc.) were analyzed. Mass concentrations of WSOC and WSIC exhibited
      higher levels in SF and HS, and high WSOC/OC ratios (67.4%) on average were
      found. Stronger correlations between WSOC and K+, Cl- occurred in SF, which might
      due to contributions of firework emissions. Six major sources of PM2.5 were
      quantified by PMF model, which contributed in aerosol mass differently in
      different periods: biomass & firework burning exhibited higher contribution
      (11.2%) in SF; crustal dust accounted for 19.4% during NHS; secondary particles
      contributed most (41.0%) in HS; during SF and HS, coal combustion devoted more to
      aerosol mass. Contributions to WSOC were in the order of vehicular exhaust (41.0%
      of WSOC) > coal combustion (29.3%) > secondary formation (17.0%) > biomass &
      firework burning (12.7%). The 82.0% of WIOC were from coal combustion and the
      rest were devoted by vehicular exhaust. Obvious peaks of firework burning
      contributions to WSOC were observed on SF's Eve and Lantern Festival. Coal
      combustion contributed to organic carbons highly in SF and HS. Results implied
      that anthropogenic activities contributions, like firework burning and coal
      combustion, significantly influenced the levels of PM2.5 and WSOC.

PMID- 30114568
TI  - Concentrations and potential health risks of strontium in drinking water from
      Xi'an, Northwest China.
AB  - Information about the concentrations of strontium (Sr(II)) in drinking water in
      China and the corresponding health risks to Chinese residents is lacking. This
      study investigated Sr(II) in drinking water through a monthly sampling campaign
      in twelve locations in Xi'an, Northwest China. A health risk assessment for
      different age groups and exposure pathways were carried out by Monte Carlo
      simulation. The results show Sr(II) concentrations of 0.06-1.69 mg/L in all
      drinking water samples, which exceeded the minimum reporting level (MRL) of 0.3
      MUg/L. Also, one sample exceeded the health reference level (HRL) of 1500 MUg/L.
      Higher Sr(II) levels were recorded in groundwater supply zones and springs, and
      more potential changes in Sr(II) occurred in distribution pipes transporting
      groundwater. The non-carcinogenic risk associated with Sr(II) exposure via
      drinking water was less than 1, indicating no significant health risk to the
      residents of Xi'an. As the first attempt to provide information on the health
      risks of Sr(II) in drinking water in China, findings from this study can be
      useful for the development of potential strategies for risk control and
      management.

PMID- 30114569
TI  - On the sensitivity of event-related fields to recollection and familiarity.
AB  - The sensitivity of event-related potentials (ERPs) to the processes of
      recollection and familiarity has been explored extensively, and ERPs have been
      used subsequently to infer the contributions these processes make to memory
      judgments under a range of different circumstances. It has also been shown that
      event-related fields (ERFs, the magnetic counterparts of ERPs) are sensitive to
      memory retrieval processes. The links between ERFs, recollection and familiarity
      are, however, established only weakly. In this experiment, the sensitivity of
      ERFs to these processes was investigated in a paradigm used previously with ERPs.
      An early frontally distributed modulation varied with memory confidence in a way
      that aligns it with the process of familiarity, while a later parietally
      distributed modulation tracked subjective claims of recollection in a way that
      aligns it with this process. These data points strengthen the argument for
      employing ERFs to assess the contributions these processes can make to memory
      judgments, as well as for investigating the nature of the processes themselves.

PMID- 30114571
TI  - Assessment of the treatment efficiency of an urban stormwater pond and its impact
      on the natural downstream watercourse.
AB  - During the last few decades, stormwater ponds have become an alternative
      management practice in order to avoid flooding and to contain rainwater and
      runoff in urban areas where impervious land cover has increased. A second purpose
      of stormwater ponds is to improve the quality of runoff water that is usually
      contaminated with nitrogen, phosphorus, metals and organic micropollutants.
      Processes used are based on natural methods such as settlement and contribute to
      minimize the impact of these inputs to the natural aquatic system. This study
      aims to better understand the behavior of a wet stormwater pond, Heron Lake (33
      ha) located in the city of Villeneuve d'Ascq in northern France through various
      indicators [trace metals, PAHs, PCBs, caffeine (CAF), carbamazepine (CBZ),
      nutrients and pathogens]. For that purpose, water quality was monitored for 1
      year, mainly at the entrance and at the outlet of the lake. Sampling have also
      been done in the downstream aquatic environment, the Marque River. Sediments were
      sampled in the lake to evaluate the pollution trapped during sedimentation. Our
      results of both water and sediment sampling highlight: (i) the wastewater input
      into the Heron Lake is estimated to be equivalent to that of roughly 3800
      inhabitants; (ii) the removal rates observed at the outlet, relative to
      concentrations at the entrance channel, vary as follows for these dissolved
      species: 24% for NO3- and PO43-, 28% for CBZ, 35% for Cu, 63% for Pb, 78% for
      CAF, 84% for Zn and up to 93% for NH4+; (iii) there are high levels of sediment
      contamination with metals, PAHs and PCBs at the entrance channel; (iv) the
      eutrophication of this pond is attributed to persistent high nutrient
      concentrations in both water and sediment, and has contributed to the development
      of an invasive macrophyte, the Elodea nuttallii; and (v) there appears to be only
      a negligible impact of the discharge from the lake to the natural watercourse,
      contributing annual loads of <2 up to 6% of the total amount of Cu, Pb, Zn, CAF,
      CBZ and nutrients measured in the Marque River, and having a slight diluting
      effect on concentrations in the Marque River.

PMID- 30114570
TI  - Electrochemical disinfection of bacterial contamination: Effectiveness and
      modeling study of E. coli inactivation by electro-Fenton, electro-peroxi
      coagulation and electrocoagulation.
AB  - The present work undertakes an examination and comparison of electro-Fenton (EF),
      electro-peroxi-coagulation (EPC) and electrocoagulation (EC) applied to the E.
      coli inactivation in batch reactor. Indeed, platinum (Pt (anode), EF), stainless
      steel (SS (cathode), EF, EPC) and ordinary steel (Fe (anode), EPC) and aluminum
      (Al, EC) were used respectively. The current intensity, nature of electrolytic
      support, bacterial density and hydrogen peroxide (H2O2) concentration are the
      most influenced study parameters. The obtained results showed that the high
      current intensities were significant for better inactivation and destruction of
      E. coli cells and caused a maximum of energy consumption. Both disinfection and
      energy consumption were improved by adding NaCl (or Na2SO4) in the three
      processes. Higher cellular density limited the electrochemical process and has
      negative effect in E. coli inactivation and the energy consumption. Only in the
      EPC case, the disinfection was considerably increased in function with H2O2
      concentration. The modeling parameters of the inactivation kinetics of E. coli
      showed a good fitting of the established model (0.9560 < R2 < 0.9979, 0.9267 < R2
      adjusted <0.997 and 0.0189 < RMSE <0.4821), faster kinetics of E. coli
      inactivation (significant values of Kmax and Sl) in the case of high current
      intensity (0.2442<Kmax<0.7440 and 10.50 < Sl < 24.69), the presence of chlorides
      or sulfates (0.6662<Kmax<0.7818 and 11.67 < Sl < 18.59), and the sufficient H2O2
      concentration (0.4712<Kmax<0.9204 and 13.00 < Sl < 16.38). Moreover, the analysis
      of the results revealed that the EF is more effective in terms of the E. coli
      inactivation and the energy consumption comparatively to the other studied
      processes.

PMID- 30114572
TI  - CO2 capture and storage: A way forward for sustainable environment.
AB  - The quest for a sustainable environment and combating global warming, carbon
      capture, and storage (CCS) has become the primary resort. A complete shift from
      non-renewable resources to renewable resources is currently impossible due to its
      major share in energy generation; making CCS an imperative need of the time. This
      study, therefore, aims to examine the reckoning of carbon dioxide (CO2),
      measurement methods, and its efficient capture and storage technologies with an
      ambition to combat global warming and achieve environmental sustainability.
      Conventionally, physical, geological and biological proxies are used to measure
      CO2. The recent methods for CO2 analyses are spectrometry, electrochemical gas
      sensors, and gas chromatography. Various procedures such as pre, post, and
      oxyfuel combustion, and use of algae, biochar, and charcoal are the promising
      ways for CO2 sequestration. However, the efficient implementation of CCS lies in
      the application of nanotechnology that, in the future, could provide a better
      condition for the environment and economic outlooks. The captured carbon can be
      stored in the earth crust for trillions of years, but its leakage during storage
      can raise many issues including its emissions in the atmosphere and soil
      acidification. Therefore, global and collective efforts are required to explore,
      optimize and implement new techniques for CCS to achieve high environmental
      sustainability and combat the issues of global warming.

PMID- 30114573
TI  - Landscape dimension in the built environment: The spatial operative of an
      integrated micro agriculture unit.
AB  - The rapid urbanization creates an increased demand for food supply and security
      in urban system. The imminent risks stemmed from climate change appeal for a
      greater effort in an overhaul of the customary practices in the planning and
      management of the urban systems. Urban centers should accommodate the growing
      need for green infrastructure and edible landscape; options such as farming
      alternative has gained interest as a possible solution to the urban-scape and the
      food production stability for the urban inhabitants. This article presents the
      systemic approach to building integrated agriculture unit prototype's design
      thinking and proposed a prototype model allowing the locality and place to be
      incorporated into the design framework. The research concludes that: (1) in line
      with human-nature connection and raising its priority level within both design
      research and design practice should consider the environmental, social, economic
      and spatial criteria for the design thinking exploration; (2) the design results
      in a flexible system model of the micro building integrated agriculture unit,
      allowing the units to fit either indoor or outdoor, as a probable solution suited
      for the locality and the increasing demand for edible greens; (3) indoor units
      need further study in integration with the indoor climate control and automation
      as well as added indoor air purification and sensor functions. (4) Prototype
      units should be capable of providing locally available edible production and
      social well-being for the urban system.

PMID- 30114574
TI  - Optimizing the H3PO4 leaching conditions of post-precipitated sewage sludge using
      response surface methodology.
AB  - The leaching procedure of post-precipitated aluminium phosphate sludge with
      dilute phosphoric acid was developed. The leaching offers a route to recover both
      critical phosphorous from sewage sludge and the metal used in precipitation.
      Using phosphoric acid as leaching solution makes it possible to continue the
      recovery process without the need to remove chloride or sulfate anions. The
      optimization of the leaching was based on experimental three-level-four-variable
      central composite face-centered design. The four variables included were acid
      concentration, volume of acid, temperature and time of leaching. The leaching was
      conducted for dewatered and water-containing sludge (total solid content 3-4%)
      and for both second-order regression models were obtained. For water-containing
      sludge optimal conditions for leaching are solid to liquid ratio (S/L) 400 gL-1,
      a temperature of 60  degrees C and a leaching time of 6 h. For the dewatered
      sludge, optimal leaching is attained when S/L ratio 119 gL-1 with 2 M acid is
      used at a temperature of 20  degrees C. The obtained results enable the
      developing of full-scale process where phosphate in the sludge is refined to
      phosphorous acid and metal used in sludge production recycled back to
      precipitation.

PMID- 30114575
TI  - Selective separation of Cu, Ni and Ag from printed circuit board waste using an
      environmentally safe technique.
AB  - Printed circuit boards (PCBs) make up a large part of e-waste and include high
      concentrations of high-value metals. Therefore, the recovery of these metals is
      interesting from both the environmental and economic points of view. Here, the
      extraction/separation of copper, nickel and silver from PCB leachate was studied
      using an aqueous two-phase system (ATPS) formed by triblock copolymers with an
      electrolyte and water, which is in compliance with the principles of green
      chemistry. The best conditions for the selective extraction consisted of 1-(2
      pyridylazo)-2-naphthol (3.5 mmol kg-1) at pH = 6.0 in 6 sequential steps for the
      Cu(II), dimethylglyoxime (5.00 mmol kg-1) at pH = 9.0 for the Ni(II) and
      thiocyanate (5.20 mmol kg-1) at pH = 9.0 for the Ag(I). These conditions were
      applied sequentially for extraction of Cu, Ni and Ag from the PCB leachate,
      obtaining high separation factor (S) values between the analyte and the metallic
      concomitants (SCu,Ni = 1,460, SCu,Fe = 15,500, SCu,Ag = 15,900, SNi,Fe = 32,700,
      SNi,Ag = 34,700 and SAg,Fe = 4800). The maximum extraction percentages (%E) for
      Cu, Ni and Ag were 99.9%, 99.9% and 99.8%, respectively. After the extraction, a
      single step stripping process was performed, resulting in more than 82% of the
      ion available in a clean lower phase. For the first time, an ATPS has been used
      for sequential extraction of several metal analytes from a real sample.

PMID- 30114576
TI  - Biophysiological and factorial analyses in the treatment of rural domestic
      wastewater using multi-soil-layering systems.
AB  - Multi-soil-layering (MSL) system was developed as an attractive alternative to
      traditional land-based treatment techniques. Within MSL system, the environmental
      cleanup capability of soil is maximized, while the soil microbial communities may
      also change during operation. This study aimed to reveal the nature of
      biophysiological changes in MSL systems during operation. The species diversity
      in soil mixture blocks was analyzed using Illumina HiSeq sequencing of the 16S
      rRNA gene. The interactive effects of operating factors on species richness,
      community diversity and bacteria abundance correlated with COD, N and P removal
      were revealed through factorial analysis. The results indicated the main factors,
      aeration, bottom submersion and microbial amendment, had different significant
      effects on microbial responses. The surface area and porosity of zeolites in
      permeable layers decreased due to the absorption of extracellular polymeric
      substances. The findings were applied for the design and building of a full-size
      MSL system in field and satisfied removal efficiency was achieved. The results of
      this study can help better understand the mechanisms of pollutant reduction
      within MSL systems from microbial insights. It will have important implications
      for developing appropriate strategies for operating MSL systems with high
      efficiency and less risks.

PMID- 30114577
TI  - Elucidating efficacy of biomass derived nanocomposites in water and wastewater
      treatment.
AB  - In the present study, two synthesis methods of nanocomposites-one involving a
      mixture of biomass and the other using chemical modification were investigated to
      evaluate practical application of green approach in pollution control,
      specifically for water and wastewater treatment. Newer multifunctional
      superparamagnetic nanocomposites using biomaterials such as unripened fruit of
      Cassia fistula (Golden shower) and Aloe vera were developed as an example of
      green approach while chemical modification was illustrated using n-octanol. Two
      specific model applications were studied for the developed materials-dye removal
      (Methyl Blue and Congo Red) and disinfection-demonstrating antimicrobial
      property. To elucidate the multifunctional character, the texture, morphology and
      composition of the prepared bionanocomposites were studied. The surface area
      values were 6.2 and 9.8 m2/g for Aloe vera and octanol based nanocomposites while
      the average pore diameters were 1.79 nm and 5.7 nm respectively, indicating
      presence of highly developed micropores in the first material having a honeycomb
      shape and the later showing excellent staircase type formation with larger pores.
      A very high dye removal to the extent of 100% was obtained that can be attributed
      largely to the functionalities imparted from Cassia fistula compared to
      ingredients from Aloe vera and octanol. The nanomaterials could be completely
      separated with absolute ease by applying simple magnetic field. Also, successful
      application of the developed materials in disinfection, removal of E. coli, was
      demonstrated with a very high efficiency of over 95%. The biomass derived
      nanocomposites exhibit excellent pollutant removal and disinfection properties,
      even at very low nanoparticle content; octanol based material indicating ~5 times
      lowered cost, while the Aloe vera based bionanocomposites have potential for cost
      reduction to the extent of 10 times as compared to only magnetite nanoparticles,
      thereby highlighting techno-economical alternative in water and wastewater
      treatment.

PMID- 30114578
TI  - The influence of impulsivity and the Dark Triad on self-reported aggressive
      driving behaviours.
AB  - The present study tested the role of Dark Triad traits (DT; narcissism,
      psychopathy, and Machiavellianism) as potential contributors to self-reported
      aggressive driving alongside driving anger, general aggression, impulsiveness,
      and attributions of malign driving intent. Members of the general community (N =
      168) completed an online survey battery measuring these characteristics, and a
      proxy measure of aggressive driving. Regression analyses revealed that
      psychopathy, a history of physical aggression towards others, and the "progress
      impeded" aspect of driving anger, accounted for 50.8% of the variance in self
      reported aggressive driving behaviours. The remaining variables were not
      significant. A structural equation model found all measures fitted into a single
      model in which impulsivity and the DT predicted general aggression, general
      aggression fully mediated the effect of the DT on driving anger, and general
      aggression and progress impedance predicted self-reported aggressive driving (GFI
      = 0.925). These results indicate tendencies toward expressing aggression
      physically, frustration at goals being impeded, and a callous, impulsive nature
      can predispose an individual to aggressive driving behaviours. Implications of
      these findings and recommendations for research are discussed.

PMID- 30114579
TI  - Raman spectroscopy based differentiation of typhoid and dengue fever in infected
      human sera.
AB  - This study investigated the potential of Raman spectroscopy, to differentiate
      between two different types of human pathological conditions with some symptom
      similarity; typhoid and dengue. Raman spectra were recorded from 20 Salmonella
      Typhi infected and 22 dengue virus (DENV) infected sera samples using laser
      wavelength 785 nm. When Raman spectrum (540 to 1830 cm-1) of serum samples was
      compared it showed significant variations. Twelve characteristic Raman bands at
      562, 649, 716, 780, 838, 1099, 1144, 1156, 1260, 1386, 1556 and 1746 cm-1 were
      recorded specifically in case of the typhoid infected samples, whereas four Raman
      bands at 756, 1218, 1672 and 1686 cm-1 were found specifically in the DENV
      infected samples. For statistical differentiation principal component analysis
      (PCA) and linear discriminant analysis (LDA) was applied which successfully
      separated two sets of data. These disease specific Raman signatures may be
      labeled as biomarkers for identification as well as differential diagnosis of
      typhoid and dengue infection. Hence we propose that Raman spectroscopy has the
      potential to not only identify but also to differentiate between different
      pathological conditions, having some similar symptoms like high grade fever in
      this case.

PMID- 30114581
TI  - Transport and retention of silver nanoparticles in soil: Effects of input
      concentration, particle size and surface coating.
AB  - Soils are considered as a major sink for engineered nanoparticles (ENPs) because
      of their inevitable release to the subsurface environment during production,
      transportation, use and disposal processes. In this context, the transport and
      retention of silver nanoparticles (AgNPs) with different input particle
      concentration, particle size, and surface coating were investigated in clay loam
      using water-saturated column experiments. Our results showed that the mobility of
      AgNPs in the soil was considerably low, and >73.9% of total injected AgNPs
      (except for no coating condition) was retained in columns. This is primarily due
      to the high specific surface area and favorable retention sites in soil.
      Increased transport of AgNPs occurred at higher input concentration and smaller
      particle size. The presence of surface coatings (i.e., polyvinylpyrrolidone (PVP)
      and citrate) further promoted the transport and reduced the retention of AgNPs in
      soil, which is likely due to their effective blocking of the solid-phase sites
      that are originally available for AgNPs retention. Although the shape of
      retention profiles (RPs) of AgNPs was either hyperexponential or nonmonotonic
      that is different from the colloid filtration theory prediction, the 1-species
      (consider both time- and depth-dependent retention) and/or 2-species (account for
      the release of reversibly deposited AgNPs) model successfully described the
      transport behaviors of AgNPs in soil columns under all the investigated
      conditions. This study proves the applicability of mathematical model in
      predicting the fate and transport of ENPs in real soils, and our findings
      presented herein are significant to ultimately develop management strategies for
      reducing the potential risks of groundwater contamination due to ENPs entering
      the environment.

PMID- 30114580
TI  - Univariate calibrations with or without chemometric assistance for determination
      of drugs lacking peak maxima in their zero-order profiles.
AB  - Trandolapril has no sharp peak in its zero-order spectrum and therefore, it is
      difficult to be measured by direct spectrophotometry. In this manuscript, several
      univariate and multivariate spectrophotometric methods were developed and
      validated for determination of Trandolapril (TR) and Verapamil (VR) combination.
      The first method for measuring Trandolapril is Constant Multiplication-Spectrum
      Subtraction (CM-SS), where Trandolapril was measured at 210 nm in its zero-order
      curve after elimination of Verapamil spectrum. Second and third methods are two
      Base Points (2BP) and area under the curve (AUC) to measure Trandolapril
      concentration without depending on the shoulder peak. The fourth method for
      Trandolapril is Derivative Subtraction (DS) that utilizes the sharp peak appeared
      in the first order spectrum of Trandolapril. Verapamil was determined by two
      methods, Constant Multiplication (CM) and Derivative Subtraction-Constant
      Multiplication (DS-CM). Also, two multivariate methods were developed for
      measurement of the mixture, Partial Least Squares (PLS) and Principal Component
      Regression (PCR). All the developed methods were validated as per ICH guidelines
      and the results proved that the developed methods are accurate and selective.
      Moreover, a statistical comparison between the developed methods and a reference
      method was done. Also, One-way ANOVA statistical test was done between all the
      proposed univariate and multivariate spectrophotometric methods.

PMID- 30114582
TI  - A cyclodextrin polymer membrane-based passive sampler for measuring triclocarban,
      triclosan and methyl triclosan in rivers.
AB  - In recent years, extensive attention has been paid to the passive sampling
      technology of diffusive gradients in thin films (DGT) due to its growing
      application in the measurement of a widening variety of compounds. Within any DGT
      device, the binding phase is a key component, and seeking novel binding phases is
      an issue worth studying. Cyclodextrin polymer, as a green and eco-friendly
      material, may be a good choice for measuring organic chemicals. In this study, a
      novel DGT sampler with cyclodextrin polymer membrane (CDPM) as the binding phase
      was developed for measuring the concentrations of triclosan, triclocarban and
      methyl triclosan. Firstly, the type and content of cyclodextrin used in CDPM was
      optimized, and a series of tests showed that CDPM had good hydrophilicity,
      thermal stability, fast uptake rate and sufficient uptake capacity, thus CDPM was
      determined to be suitable for use as the binding phase of DGT sampler. Moreover,
      the sampling rates of this DGT sampler were not influenced by ionic strength and
      dissolved organic matter, making it feasible for in situ monitoring of compounds
      in the field. Hence, we deployed the developed DGT sampler in the Qinhuai and
      Jiuxiang Rivers to measure the concentrations of three compounds. We also
      collected water samples and processed them with the solid phase extraction (SPE)
      method. Results indicated that there was no significant difference between the
      DGT-measured and the SPE-measured concentrations for each compound, which
      confirmed the reliability of this DGT sampler for monitoring the concentrations
      of compounds in natural waters.

PMID- 30114583
TI  - Identification of sewage markers to indicate sources of contamination: Low cost
      options for misconnected non-stormwater source tracking in stormwater systems.
AB  - There has been increasing research focusing on the detection and occurrence of
      wastewater contamination in urban water systems. To find suitable markers to
      indicate industrial and domestic sewage flows inappropriately entering storm
      drains, this study investigated the occurrence and fate of 52 chemical markers
      through wastewater treatment facilities of manufacturers of agricultural and
      sideline products, beverage products, and pharmaceutical products, which are also
      consumed in our daily life. Of the 52 candidate markers, sodium, chloride,
      potassium, isomalto-oligosaccharide, acesulfame, theanine, glycerol, and
      clarithromycin were found to be conservative markers, with an average change in
      concentrations through the wastewater treatment processes of <30%. These markers
      are useful in identifying industrial and domestic sewage flow contamination in
      urban sewers. Specially, sodium, chloride, potassium, isomalto-oligosaccharide,
      acesulfame, and clarithromycin exhibited higher concentrations in blackwater than
      in greywater, with detected average concentrations of 43.8 mg/L, 189 mg/L, 37.3
      mg/L, 123 MUg/L, 37.2 MUg/L, and 0.99 MUg/L in blackwater, respectively. In
      contrast, theanine and glycerol were observed with higher concentrations in
      greywater than in blackwater (average 10.1 MUg/L and 19.5 MUg/L in greywater,
      respectively). The benchmark concentrations to discriminate between industrial
      and domestic sewage were also presented. A study in a storm drainage system of
      downstream Taihu catchment, China demonstrated the usefulness of the markers as
      low-cost options to trace and quantify misconnected wastewater entries into storm
      drains, while denoting priority areas for misconnected entries correction.

PMID- 30114585
TI  - Lessons learnt from a pilot study on residual dye removal by an aerated treatment
      wetland.
AB  - Treatment wetlands (TWs) have shown good capacity in dye removal from textile
      wastewater. However, the high hydraulic retention times (HRTs) required by these
      solutions and the connected high area requirements, remain a big drawback towards
      the application of TWs for dye treatment at full scale. Aerated TWs are
      interesting intensified solutions that attempt to reduce the TW required area.
      Therefore, an aerated CW pilot plant, composed of a 20 m2 horizontal subsurface
      flow TW (HF) and a 21 m2 Free Water System (FWS), equipped with aeration
      pipelines, was built and monitored to investigate the potential reduction of
      required area for dye removal from the effluent wastewater of a centralized
      wastewater treatment plant (WWTP). During a 8 months long study, experimenting
      with different hydraulic retention times (HRTs - 1.2, 2.6 and 3.5 days) and
      aeration modes (intermittent and continuous), the pilot plant has shown a normal
      biological degradation for organic matter and nutrients, while the residual dye
      removal has been very low, as demonstrated by the absorbance measure at three
      wavelengths: at 426 nm (blue) the removal varies from -55% at influent absorbance
      of 0.010 to 41% at 0.060; at 558 nm (yellow) the removal is negative at 0.005 (
      58%) and high at higher influent concentrations (72% at 0.035 of absorbance for
      the inlet); at 660 nm (red) -82% of removal efficiency was obtained at influent
      absorbance of 0.002 and 74% at 0.010. These results are a consequence of the
      biological oxidation processes taking place in the WWTP, so that the residual dye
      seems to be resistant to further aerobic degradation. Therefore, TWs enhanced by
      aeration can provide only a buffer effect on peak dye concentrations.

PMID- 30114584
TI  - Personal care products use and phthalate exposure levels among pregnant women.
AB  - BACKGROUND: Fetuses are susceptible to phthalates, known endocrine disrupting
      chemicals, within sensitive windows of development. It is crucial to determine
      the major sources of phthalates to reduce exposure. This study aims to examine
      the associations between usage patterns of personal care products (PCPs) and
      urinary levels of phthalate metabolites across pregnancy in a multi-hospital
      based birth cohort. METHODS: During 2012-2015, we conducted a birth cohort study
      named the Taiwan Mother Infant Cohort Study (TMICS). Usage patterns of PCPs were
      obtained using structured questionnaires during the third trimester of pregnancy.
      Spot urine samples were collected at each trimester, and levels of eleven
      phthalate metabolites were measured by liquid chromatography tandem mass
      spectrometry. The association of PCPs use with urinary phthalate metabolite
      concentrations was assessed using GEE models. RESULTS: Among the 1676 pregnant
      women participated in TMICS, 281 who provided two or three urine samples across
      pregnancy were included. The levels of several phthalate metabolites were
      significantly associated with the use of PCPs, particularly leave-on PCPs. With
      the increasing use of skin toners (11.7%; 95% CI: 1.5%, 22.9%), lipsticks (13.2%;
      95% CI: 4.6%, 22.5%), and essential oils (21.8%; 95% CI: 9.1%, 36.0%),
      individuals are exposed to higher concentrations of mono-ethyl phthalate (MEP).
      Additionally, a positive trend was found regarding the number of leave-on PCPs
      used and the measured change in MEP concentrations (P for trend = 0.01). Other
      positive associations included MBzP and body lotions (7.9%; 95% CI: 0.1%, 16.2%).
      With regard to rinse-off PCPs, we found a positive association between urinary
      MBzP and shampoo use, and a negative association between urinary MMP and face
      wash. CONCLUSION: Leave-on PCPs were found to be a more probable source of
      phthalate exposure than the use of rinse-off PCPs. We suggest pregnant women
      reduce the frequency of leave-on PCPs use during pregnancy to avoid such
      phthalate exposure.

PMID- 30114586
TI  - Proximate, fatty acids and metals in edible marine bivalves from Italian market:
      Beneficial and risk for consumers health.
AB  - Seafood is recognized as a healthy food choice due to high contents of essential
      nutrients, including polyunsaturated fatty acids (PUFAs) of the n-3 family.
      However, seafood is often contaminated by toxic compounds, which have adverse
      effects on human health. The aim of this study was to provide information about
      the percentage of edible part, condition index and the benefit and risk for human
      consumers health associated to the consumption of eight bivalve species
      (Flexopecten glaber, Mimachlamys varia, Modiolus barbatus, Mytilus
      galloprovincialis, Ostrea edulis, Ruditapes philippinarum, Solen marginatus and
      Venus verrucosa) of high commercial value, purchased from Taranto local fish
      markets. High percentage of edibility and condition index were found in all
      analysed species. The relatively high protein content, low levels of lipid and
      high percentage of healthy n-3 PUFAs make M. varia, O. edulis, S. marginatus, M.
      galloprovincialis, M. barbatus more suitable for benefit to consumers.
      Provisional tolerable weekly intake and hazard index calculated on the basis of
      trace metals in edible tissues, indicated specific recommendations for a
      responsible daily consumption of shellfish. For the most part of studied species,
      the estimated balance between beneficial and risk for consumers recommend a daily
      portion (RDP) lesser of 60 g/person/day than M. galloprovincialis, O. edulis and
      R. philippinarum (>=60 g/person/day). Careful risk-benefit considerations should
      promote seafood consumption while minimizing exposure to toxic contaminants.

PMID- 30114587
TI  - Linking watershed modeling and bacterial source tracking to better assess E. coli
      sources.
AB  - Terrestrial fate and transport processes of E. coli can be complicated by human
      activities like urbanization or livestock grazing. There is a critical need to
      address contributing sources of bacterial contamination, properly assess the
      management of critical sources, and ultimately reduce E. coli concentrations in
      impaired water bodies. In particular, characterization of wildlife animal
      contributions and other "background" input sources of microbial pollution are
      highly uncertain and data are scarce. This study attempts to identify critical
      sources of E. coli and the efficacy of conservation practices for mitigating E.
      coli concentrations in the Arroyo Colorado watershed, Texas, using a process
      based hydrologic and water quality model. We propose to incorporate a bacterial
      source tracking assessment into the modeling framework to fill the gap in data on
      wildlife and human contribution. In addition, other sources identified through a
      GIS survey, national census, and local expert knowledge were incorporated into
      the model as E. coli sources. Results suggest that simulated distribution of E.
      coli sources significantly improved after incorporating this enhanced data on E.
      coli sources into the model (R2 = 0.90) compared to the SWAT result without BST
      (R2 = 0.59). Scenario assessments indicate that wildlife contributions may remain
      significant despite land use change and urbanization, expected to mostly occur in
      agricultural and range lands. A combination of nonpoint source management
      measures, voluntary implementation of advanced treatment by wastewater plants
      where possible, and installation of aerators in the zone of impairment were
      demonstrated to be effective measures for restoring the recreation and aquatic
      life uses of the Arroyo Colorado.

PMID- 30114588
TI  - Evaluation of metal oxides and activated carbon for lead removal: Kinetics,
      isotherms, column tests, and the role of co-existing ions.
AB  - Activated carbon (AC) is commonly used in faucet and pitcher filters for lead
      (Pb(II)) removal in homes. This study evaluated the Pb(II) removal performance of
      AC and metal oxides (e.g. Fe(OH)3 and TiO2), as well as the co-existing ions'
      effect on Pb(II) removal. Results showed that metal oxides had higher adsorption
      capacity (28.9-51.5 mg/g) than AC (21.2 mg/g). Pb(II) was inner-spherically
      adsorbed onto both AC and metal oxides surfaces. Among various metal ions,
      calcium (Ca(II)) demonstrated dramatic effects on Pb(II) removal ability of AC,
      while it had no effect on Pb(II) adsorption by metal oxides. This difference
      resulted from the inner- and outer-sphere adsorption of Ca(II) on AC and metal
      oxides, respectively. The presence of orthophosphate (orth-P) and sulfate
      enhanced Pb(II) removal by those three adsorbents, whereas carbonate and silicate
      had negligible effect on Pb(II) adsorption. Interestingly, while the orth-P was
      usually used as corrosion inhibitor because of the formation of lead-phosphate
      coprecipitate, we found that the enhanced effect of orth-P on Pb(II) removal was
      mainly due to the synergistic adsorption. This study provides valuable
      information for the selection of effective adsorbents for Pb(II) removal and is
      helpful for understanding the roles of co-existing ions on it.

PMID- 30114589
TI  - Sustainability assessment of home-made solar cookers for use in developed
      countries.
AB  - The sustainability benefits of using solar cookers in developing countries have
      been analysed widely in the literature. However, the sustainability potential of
      solar cookers in developed economies has not been explored yet, which is the
      topic of this paper. Three types of solar cooker - box, panel and parabolic -
      were built as part of this research, using mostly (>70%) reused household
      materials. Their life cycle environmental and economic performance was analysed
      and compared to conventional microwaves. The results were first considered at the
      level of individual cookers and then scaled up to the levels of a city, region
      and country, considering a conservative (10%) uptake of solar cookers in
      substitution of microwaves. The contribution of home-made solar cookers to a
      circular economy and their social sustainability were also analysed. Spain was
      used as an illustrative example to demonstrate the potential sustainability
      benefits of using solar cookers in developed countries. The results suggest that,
      in comparison with microwaves, they could reduce annual life cycle costs by up to
      40% and environmental impacts by up to 65%, including greenhouse gas emissions.
      At the national level, 42,600 t of CO2 eq. would be avoided annually while the
      consumption of primary energy would be reduced by 860 TJ. Furthermore, the
      electricity consumption would decrease by 67 GWh/yr and 4200 t/yr of household
      waste would be avoided. If solar cookers were built entirely by reusing household
      materials, up to ?23.2 million could be saved per year. Finally, the development
      of craft activities to build and repair the cookers can help people to engage
      socially and reduce stress, thus enhancing their social wellbeing. It can also
      increase people's awareness of a more sustainable use of resources. Therefore,
      home-made solar cookers represent a promising opportunity to motivate behavioural
      changes towards a circular economy and sustainability in developed countries.

PMID- 30114590
TI  - Origin and fate of nitrate runoff in an agricultural catchment: Haean, South
      Korea - Comparison of two extremely different monsoon seasons.
AB  - The monsoon season in South Korea has great influences on biogeochemical and
      hydrological processes in the entire country, but is specifically of concern in
      the Soyang lake watershed, the main drinking water reservoir for the 20-million
      people metropolis Seoul. Therefore, water quality and nitrate concentration
      control in Lake Soyang is of high public priority. The Haean catchment is the
      most prominent agriculture-dominated sub-catchment of the Soyang lake watershed.
      It is a complex terrain influenced by extreme rain events and non-point nitrate
      sources. In this investigation we used input-output calculations and a stable
      isotope approach to quantify and determinate the origin of nitrate inputs into
      the rivers that later flow into the lake. During pre-monsoon and monsoon seasons
      in 2013 and 2014 we measured daily rainfall and river water discharge within the
      Haean catchment and collected rain, river water and groundwater samples in order
      to analyze nitrate concentrations and nitrate nitrogen and oxygen isotope
      abundances. Furthermore, we collected nitrogen fertilizers as applied in the
      catchment. Heavy monsoon events, as in 2013, were the most pronounced drivers of
      nitrate leaching being responsible for >80% of the nitrate output in the river
      runoff. On the other hand, an almost missing summer monsoon in 2014 drove the
      nitrate runoff in a different manner, being responsible for only 0.4% of the
      total nitrate nitrogen river discharge in the previous year. Results of nitrate
      nitrogen and oxygen isotope abundance analyses suggest soil microbial
      nitrification as the most important contributor to the nitrate in the river
      runoff. In addition, nitrate from groundwater partially affected by microbial
      denitrification contributed to the nitrate in the runoff due to river-aquifer
      exchange fluxes during the monsoon season. Direct leaching of nitrate from
      mineral fertilizers and atmospheric nitrate deposition were obviously only minor
      contributors to the nitrate in the runoff.

PMID- 30114592
TI  - Metabolic and NH4 excretion rate of fresh water species, Chondrostoma regium in
      response to environmental stressors, different scenarios for temperature and pH.
AB  - Changes in water temperature and pH levels have substantial adverse effects on
      aquatic organisms, hence causing physiological constraint on their well-being. To
      understand the physiological responses of Chondrostoma regium to temperature or
      pH changes, standard metabolic rate (SMR), maximum metabolic rate (MMR), absolute
      and factorial aerobic scope (AS&FAS) as well as the specific rate of ammonia
      excretion (Jamm) were measured at following temperatures: acute low (3.5-4.5 
      degrees C), 24 h low (5.5-6.5  degrees C), 7 d low (5.5-6.5  degrees C), acute
      high (30-31  degrees C), 24 h high (29-30  degrees C), 7 d high (28-29  degrees
      C), and different pH treatments: acute low (4.3-4.4), 24 h low (4.3-4.4), 7 d low
      (6.3-6.4), acute high (9.8-9.9), 24 h high (9.8-9.9), 7 d high (8.8-8.9). A
      control group was also assigned to optimum temperature = 22-23  degrees C and pH
      = 7.8-7.9. These experimental ranges for each treatment were obtained based on
      critical thermal and pH thresholds, i.e., 1.9 to 31.7  degrees C and 2.7 to 11.1,
      respectively. SMR was enhanced significantly (P < 0.05) following pH treatments,
      except for 24 h low pH treatment. Results showed significant (P < 0.05) changes
      in both SMR and MMR at low and high temperature treatments. The AS was elevated
      following pH treatments except for acute low pH treatment in which AS
      significantly was declined (P < 0.05). Low temperature treatments resulted in
      lower AS while no significant changes in AS were observed in high temperatures.
      In all treatments, FAS value did not differ significantly from control, except
      for acute and 24 h low treatments of both temperature and pH. All high pH and
      temperature treatments showed a significant increase (P < 0.05) in Jamm.
      Histopathological results of gills indicated hyperplasia and fusion of secondary
      lamella and kidneys histopathology revealed necrosis and loss of tubular lumen in
      the most treatments. Results indicated that increases in water temperature or pH
      are more stressful than the lower ranges of them, suggesting higher capability of
      fish to adjust to the low levels of temperature or pH.

PMID- 30114593
TI  - The diversity, evolution and origins of vertebrate RNA viruses.
AB  - Despite a substantial increase in our knowledge of the biodiversity and evolution
      of vertebrate RNA viruses, far less is known about the diversity, evolution and
      origin of RNA viruses across the diverse phylogenetic range of viruses, and
      particularly in healthy animals that are often only rarely utilized for
      virological sampling. Fortunately, recent advances in virus discovery using
      metagenomic approaches are beginning to reveal a multitude of RNA viruses in
      vertebrates other than birds and mammals. In particular, fish harbor a remarkable
      array of RNA viruses, including the relatives of important pathogens. In
      addition, despite frequent cross-species transmission, the RNA viruses in
      vertebrates generally follow the evolutionary history of their hosts, which began
      in the oceans and then moved to terrestrial habitats over timescales covering
      hundreds of millions of years.

PMID- 30114591
TI  - Prediction of bioconcentration factors in fish and invertebrates using machine
      learning.
AB  - The application of machine learning has recently gained interest from
      ecotoxicological fields for its ability to model and predict chemical and/or
      biological processes, such as the prediction of bioconcentration. However,
      comparison of different models and the prediction of bioconcentration in
      invertebrates has not been previously evaluated. A comparison of 24 linear and
      machine learning models is presented herein for the prediction of
      bioconcentration in fish and important factors that influenced accumulation
      identified. R2 and root mean square error (RMSE) for the test data (n = 110
      cases) ranged from 0.23-0.73 and 0.34-1.20, respectively. Model performance was
      critically assessed with neural networks and tree-based learners showing the best
      performance. An optimised 4-layer multi-layer perceptron (14 descriptors) was
      selected for further testing. The model was applied for cross-species prediction
      of bioconcentration in a freshwater invertebrate, Gammarus pulex. The model for
      G. pulex showed good performance with R2 of 0.99 and 0.93 for the verification
      and test data, respectively. Important molecular descriptors determined to
      influence bioconcentration were molecular mass (MW), octanol-water distribution
      coefficient (logD), topological polar surface area (TPSA) and number of nitrogen
      atoms (nN) among others. Modelling of hazard criteria such as PBT, showed
      potential to replace the need for animal testing. However, the use of machine
      learning models in the regulatory context has been minimal to date and is
      critically discussed herein. The movement away from experimental estimations of
      accumulation to in silico modelling would enable rapid prioritisation of
      contaminants that may pose a risk to environmental health and the food chain.

PMID- 30114594
TI  - Mourning our dead: The impact of Mexico's war on drugs on citizens' depressive
      symptoms.
AB  - BACKGROUND: Research has shown the substantial impact on mental health for
      victims of drug-related crime in Mexico, especially individuals who have been
      heavily exposed to violence. However, the effect of drug-related violence in non
      victims has been less studied because causal pathways via indirect violence are
      more ambiguous. We argue that drug-related violence does have an influence on the
      mental health of non-victims: For example, because of how violence is publicized
      by criminal groups, including their use of gruesome killing methods in
      executions, or via news about government confrontations with these criminal
      groups. METHODS: We estimate linear models of the effect of drug-related violence
      (CIDE-PPD database) on depression symptoms (MxFLS 2009-2012). We use lagged
      violence variables to match the time when individuals' depression symptoms were
      reported, using different proxies of violence. FINDINGS: Our findings suggest a
      negative effect of drug-related violence on the mental health of individuals,
      specifically in relation to communication used by criminal groups
      (narcomessages), the brutality of executions, and the confrontations between
      government forces (specifically local police) and criminal groups. CONCLUSIONS:
      Our findings suggest that the general population is a direct victim of the
      psychological violence imposed by the use of narcomessages. This additional
      effect of the war on drugs should be considered when deciding how to address the
      psychological effects of drug-related violence. The government should provide
      safer public spaces to improve perceptions about security, and more mental health
      services in communities that are most affected by organized crime violence.
      Mental health is also affected when police forces fight criminal groups. These
      findings corroborate the crisis of local institutions, the low confidence
      citizens have in police, and/or the infiltration of organized crime in local
      police corps. Mexico requires police reform, not only to avoid the involvement of
      the military in public security operations, but also to avoid social and
      psychological damage produced by weak police forces fighting organized crime.

PMID- 30114596
TI  - Synthesis and anticoagulation studies of "short-armed" fucosylated chondroitin
      sulfate glycoclusters.
AB  - Fucosylated chondroitin sulfate (FuCS) is a structurally complex
      glycosaminoglycan found in sea cucumbers with a wide spectrum of biological
      activities, among which anticoagulant activity is particularly attractive for the
      development of alternative anticoagulant drugs with decreased adverse effects and
      risks of bleeding. Previous studies show that FuCS glycomimetics bearing several
      trisaccharide epitopes displayed promising anticoagulant activity and did not
      change the mode of action of FuCS. To simplify synthetic difficulty of high
      valent glycoclusters and obtain candidate compounds with relatively low molecular
      weights, here we report the synthesis of two FuCS glycoclusters with low valence
      and more compact structures. Anticoagulation studies showed that these simplified
      "short-armed" glycoclusters demonstrated comparable potency with "long-armed"
      high valent glycoclusters, offering a concise approach for the development of
      novel anticoagulant agents.

PMID- 30114597
TI  - Investigation of inner mechanism of anisotropic mechanical property of antler
      bone.
AB  - Bones have different functions and various applications depending on the roles
      they play in different mammal bodies. The internal relationships between the
      functions and microstructures of bones need further expounding to understand
      their specific mechanical properties. In this study, the relationships between
      the mechanical properties and microstructures of the compact bone of antler
      (called as antler bone for short) along its three different orientations are
      investigated. First, the bending mechanical properties of the specimens of the
      antler bone along its three different orientations are tested with material
      testing machine, followed by the observations of the crack-extending routes and
      the fracture surfaces of the three different orientations with a scanning
      electron microscope (SEM). The results of the tests reveal that the antler bone
      possesses anisotropic mechanical property. Namely, the mechanical properties of
      the antler bone are closely related to its orientations. Concretely, the fracture
      strength, elastic modulus and work-of-fracture along the transversal orientation
      of the bone are remarkably larger than those of the longitudinal and radial
      orientations. The results of the observation of the SEM show that there are
      different crack-extending routes and fracture-surface characteristics along the
      three different fracture orientations of the bone. Specifically, there are crack
      deflections and crack twists along the transversal fracture orientation, crack
      bridging along the longitudinal fracture orientation and crack rounding of
      osteons along the radial fracture orientation. Based on the tested and observed
      results, the fractal models of the crack-extending routes along the three
      different fracture orientations are presented. The fractal dimensions and
      critical crack extension forces along the three different fracture directions are
      calculated based on the fractal models. Further, the box-counting method is
      adopted to verify the correctness of the models. It is indicated that the fractal
      dimension and fracture energy of the transversal orientation are obviously larger
      than those of the longitudinal and radial orientations, which are in accordance
      with the experimental results.

PMID- 30114595
TI  - Establishment and Characterization of Paired Primary and Peritoneal Seeding Human
      Colorectal Cancer Cell Lines: Identification of Genes That Mediate Metastatic
      Potential.
AB  - Peritoneal metastasis is one of the major patterns of unresectability in
      colorectal cancer (CRC) and a cause of death in advanced CRC. Identification of
      distinct gene expressions between primary CRC and peritoneal seeding metastasis
      is to predict the metastatic potential of primary human CRC. Three pairs of
      primary CRC (SNU-2335A, SNU-2404A, and SNU-2414A) and corresponding peritoneal
      seeding (SNU-2335D, SNU-2404B, and SNU-2414B) cell lines were established to
      determine the different gene expressions and resulting aberrated signaling
      pathways in peritoneal metastasis tumor using whole exome sequencing and
      microarray. Whole exome sequencing detected that mutation in CYP2A7 was
      exclusively shared in peritoneal seeding cell lines. Microarray identified that
      there were five upregulated genes (CNN3, SORBS1, BST2, EPSTI1, and KLHL5) and two
      downregulated genes (TRY6 and STYL5) in the peritoneal metastatic cell lines.
      CNN3 expression was highly augmented in both mRNA and protein levels in
      peritoneal metastasis cells. Knockdown of Calponin 3 resulted in augmented level
      of E-cadherin in peritoneal metastasis cells, and migration and invasiveness
      decreased accordingly. We suggest that CNN3 takes part in cell projection and
      movement, and the detection and distribution of CNN3 may render prognostic
      information for predicting peritoneal seeding metastasis from primary colorectal
      cancer.

PMID- 30114598
TI  - Acute exposure of zebrafish embryo (Danio rerio) to flutolanil reveals its
      developmental mechanism of toxicity via disrupting the thyroid system and
      metabolism.
AB  - Flutolanil, an amide fungicide, had been detected frequently in aquatic
      environments; it is thus potentially a great risk to aquatic organisms and human
      health. Therefore, we investigated the developmental toxicity and the potential
      mechanism of thyroid endocrine disruption induced by flutolanil based on 1H NMR
      metabolomics analysis using a zebrafish model. Hatching of zebrafish embryo
      exposed to flutolanil was inhibited at 72 hpf (hour post-fertilization) and
      survival and body length at 96 hpf. In addition, increased teratogenic effects on
      embryos were observed, including pericardial edema, spine deformation, and tail
      malformation. Furthermore, flutolanil induced slower heartbeat and larger
      pericardial area in the treated groups than control group. Transcription levels
      of TRH, TSHR, TPO, Dio1, TRalpha, and UGT1ab were significantly altered after
      flutolanil exposure. Metabolomics analysis further indicated that flutolanil
      induced alterations of energy, amino acids, nucleotide, lipids, and fatty acid
      metabolism. Our study also indicated that flutolanil exposure led to alterations
      of endogenous metabolites, which induced the thyroid endocrine disruption in
      zebrafish. Ultimately, embryonic developmental toxicity was caused by flutolanil.

PMID- 30114599
TI  - Heavy metals in nectar modify behaviors of pollinators and nectar robbers:
      Consequences for plant fitness.
AB  - Plants growing in heavy-metal-rich soils can accumulate metals into their nectar.
      Nectar chemical composition can alter foraging behavior of floral visitors
      (including pollinators and floral antagonists) and further affect plant
      reproductive fitness. The role of nectar heavy metals in deterring pollinators
      (e.g., shortening foraging time) has been recently studied, but their effects on
      plant reproduction via changes in behaviors of both pollinators and floral
      antagonists (e.g., nectar robbers) are less understood. We experimentally
      manipulated four nectar heavy metals (Zn, Cu, Ni, and Pb) in a native ornamental
      plant, Hosta ensata F. Maekawa, to investigate the effect of nectar metals on
      plant reproductive success. We also recorded nectar robbing as well as foraging
      time and visitation rate of pollinators to assess whether nectar metals could
      alter the behavior of antagonists and mutualists. Although metals in nectar had
      no significant direct effects on plant reproduction via hand-pollination, we
      detected their positive indirect effects on components of female fitness mediated
      by pollinators and nectar robbers. Matching effects on female plant fitness,
      nectar robbers responded negatively to the presence of metals in nectar, robbing
      metal-treated flowers less often. Pollinators spent less time foraging on metal
      treated flowers, but their visitation rate to metal-treated flowers was
      significantly higher than to control flowers. Moreover, pollinators removed less
      nectar from flowers treated with metals. Our results provide the first direct
      evidence to date that heavy metals in nectar are capable of deterring nectar
      robbers and modifying pollinator foraging behavior to enhance plant reproductive
      fitness.

PMID- 30114600
TI  - Interactions between algal (AOM) and natural organic matter (NOM): Impacts on
      their photodegradation in surface waters.
AB  - The occurrence of algae bloom would lead to the release of algae-derived organic
      matter (AOM) and then alter the abundance and behavior of dissolved organic
      matter (DOM) in aquatic ecosystems. In this study, the characteristics and
      photodegradation of AOM, naturally occurring organic matter (NOM) derived from
      soil and plants and their mixtures were explored to reveal the potential
      interactions between AOM and NOM in water. Results indicated that the protein
      like components from AOM and the humic-like components from SRNOM took place
      inter-component interactions in the AOM-NOM mixtures. Meanwhile, application of
      two-dimensional Fourier transform infrared correlation spectroscopic (2D-FTIR
      COS) analysis revealed that carboxylic C=O had a high priority to bind with other
      functional groups (e.g., phenolic-OH, polysaccharides C-O, amideIIC-N/N-H and
      celluloses C-H). More crucially, it was found that the AOM-NOM mixtures subjected
      to a very different photodegradation behavior to their end-members (i.e., AOM and
      NOM), likely because of the occurrence of AOM-NOM interactions as well as their
      roles in mediating the yield of reactive oxygen species. For instance, the
      presence of AOM led to increased photodegradation degrees of the chromophoric
      fraction in NOM. In contrast, the NOM did not exhibit any photosensitization role
      in the photodegradation of the proteins from AOM. This study has potential
      implications for our understanding of the carbon cycling in anthropogenically
      impacted aquatic systems such as inland rivers and lakes.

PMID- 30114601
TI  - Urban soils impacted by tailings from coal mining: PAH source identification by
      59 PAHs, BPCA and alkylated PAHs.
AB  - Urban soils in mining and industrial regions like the Ruhr Area are characterized
      by admixtures of anthropogenic substrates, e. g. tailings, coals, ashes, debris
      or scoria. These soils often show elevated concentrations of polycyclic aromatic
      hydrocarbons (PAHs) which are commonly attributed to non-point pyrogenic carbon
      sources like soot and particulate matter. An emission source of PAHs into urban
      soils in these regions, that surprisingly is still largely neglected, are the
      millions of tons of tailings from underground coal mining that have been used as
      material for road construction, terrain leveling, river channeling and support of
      embankments. Here we classify the PAH sources of 13 urban soils as either
      petrogenic or pyrogenic. The soils contained (1) tailings, (2) ashes and (3)
      different anthropogenic substrates. The classification is based on a
      comprehensive analysis of 59 PAHs and alkylated PAH distributions by GC-MS and
      BPCA analyses by LC-TOF-MS. PAH concentrations (?59 PAHs) of all soils ranged
      from 60 to 140 mg/kg, except one soil showing 559 mg/kg. The PAH source in the
      urban soils containing tailings was identified as petrogenic carbon due to (1)
      the dominance of low molecular weight PAHs, (2) bell shape distribution patterns
      of the alkylated PAHs, and (3) comparable BPCA distribution patterns to
      bituminous coals. In contrast, the PAH source of the ash-containing soil was
      identified as pyrogenic carbon by high molecular weight PAH percentages >80%,
      slope shape distribution patterns of the alkylated PAHs and a higher degree of
      aromatic condensation (B6CA/BPCA) than bituminous coals, coal ashes or charcoal.
      The urban soils containing different anthropogenic substrates revealed the
      occurrence of both a petrogenic and a pyrogenic PAH source. Surprisingly, the
      separate analyses of isolated coal ash particles revealed typical petrogenic
      indicators showing that by visual approach coal ashes cannot generally be
      classified as being of a pyrogenic PAH source.

PMID- 30114602
TI  - TAome analysis of type-II toxin-antitoxin system from Xenorhabdus nematophila.
AB  - Here we report the first essentially complete TAome analysis for type II toxin
      antitoxin (TA) system, a major class of TA modules found in bacterial system,
      from entomopathogenic bacterium Xenorhabdus nematophila ATCC 19061 (NCBI RefSeq
      NC_014228). We summarize this analysis in terms of TA locus, accession
      identifier, hits in conserved domain database, toxin superfamily, antitoxin
      superfamily and chromosomal/mobile genome/plasmid occurrences. Moreover, for TA
      context analyses we use six different specifications namely virulence factors,
      mobile genetic elements (MGE), antibiotic resistance genes, secretion systems,
      prophage and a classification of mobile genetic elements (ACLAME); among these
      hits are found for only MGE, ACLAME and prophage. A total 39 sets of TA have been
      discovered in which numbers of TA encoded for MGE, ACLAME and prophage are 15, 15
      and 5 respectively while the remaining four have no context hit. In addition, a
      comparative analysis of TAome was also done with closely related bacterium
      Photorhabdus luminescens subsp. laumondii TTO1 (NCBI RefSeq NC_005126) and
      results shows that a total 8 sets of TA are conserved. Further, a bootstrap
      Neighbor-Joining phylogenetic tree was also constructed for major toxin protein
      superfamily found namely RelE, HigB, GNAT, CcdB and MazF explored in the TAome of
      X. nematophila. We also characterized, the most abundantly found TA module
      (relBE) in this TAome, functionally and transcriptionally. This first TAome
      analysis of type II TA modules provides new insights in multi-drug tolerance in
      bacterial populations.

PMID- 30114603
TI  - Influence of inhibitors on the adhesion of SRB to the stainless steel in
      circulating cooling water.
AB  - Influence of the surface characteristics of three stainless steels (SS304, 316L
      and 317) and presence of scale inhibitors on adhesion kinetics of sulfate
      reducing bacteria (SRB) in circulating cooling water, were investigated by
      evaluating surface free energy, adhesion kinetic constants in a parallel plate
      flow chamber. Results show that the surface free energy values of SS317, SS316L
      and SS304 are -31.69, -24.18 and -13.92 mJ m-2, respectively. SS317 surface had
      higher surface hydrophobicity than SS316L and SS304. In the process of bacteria
      cells adhesion onto SS surfaces, electrostatic interaction for SS is slightly
      more than hydrophobic interaction. The number of adhering bacteria and the
      adhesion kinetic constants are different on the three types of stainless steel.
      The adhesion kinetic constants for SS317 and 316L are greater than that for
      SS304, which are 0.0354, 0.0282 and 0.0190 min-1, respectively. Scale inhibitors
      of hydrosy ethyl fork phosphonic acid (HEDP) and phosphono butane-1, 2, 4
      tricarboxylic acid (PBTCA) have a certain influence on the initial adhesion of
      bacteria cell and adhesion kinetics constants are reduced in the presence of HEDP
      and PBTCA.

PMID- 30114604
TI  - Evaluation of the efficacy of nicotine in treatment of allergic asthma in BALB/c
      mice.
AB  - Nicotine, an nAChR agonist, shows prominent anti-inflammatory properties, and
      some studies have illustrated its suppressive effects on inflammation. Here, we
      have examined whether nicotine as a medicine may have beneficial effects on the
      treatment of asthma in a mouse model of allergic asthma. BALB/c mice were
      sensitized with OVA and alum. Two weeks later, the mice received nicotine with
      concentrations of 1 and 10 mg/kg three times every other day. After 10 days, the
      mice were challenged with OVA (5%) using an ultrasonic nebulizer and died the
      next day. Our results showed that the administration of nicotine reduced lung
      tissue inflammation, the number of eosinophils in bronchoalveolar fluid, allergen
      specific IgE and IL-4 production, while it increased the TGF-beta/IL-4 ratio and
      the number of Treg cells. Our results showed that nicotine applies its
      suppressive effects in a dose-dependent manner: administration of 10 mg/kg of
      nicotine showed more suppressive effects than 1 mg/kg. Such data suggested that
      nicotine might be a good candidate to be used as a medicine in the treatment of
      allergic asthma by decreasing allergic inflammation severity and potentiating
      Treg cells proliferation against the allergen.

PMID- 30114605
TI  - MS-STEM-FEM: A parallelized multi-slice fluctuation TEM simulation tool.
AB  - Atomic configurations of glassy or amorphous materials containing medium-range
      order (MRO) may be identified by comparing fluctuation transmission electron
      microscopy (FTEM) measurements to FTEM simulations obtained using model
      configurations. Candidate model sizes have traditionally been much thinner than
      the samples measured experimentally, and publicly available FTEM simulation
      software has until now omitted microscope parameters, dynamical scattering, and
      the phase of the diffracted electron wave. We introduce MS-STEM-FEM, an open
      source software package for simulating FTEM experiments using established multi
      slice TEM simulation techniques to emulate experiment more closely by
      incorporating microscope parameters and simulating electron scattering and
      propagation as a complex valued wave. Simulations using established models are
      compared with results of experimental STEM-FEM to validate the software. Several
      statistical measures of diffraction are implemented and their responses to model
      features are compared. Dynamical scattering is found to be less influential than
      the variety of crystallite orientations which occur in thicker models.
      Simulations of variable resolution microscopy confirm that cumulative intensity
      of the FTEM signal decreases with reduced model MRO and increased coherence
      volume. Advantageous model scaling characteristics and efficient processor
      performance scaling are demonstrated, along with a study of convergence with
      respect to pertinent simulation parameters to identify accuracy requirements.

PMID- 30114606
TI  - LC-MS analysis of key components of the glutathione cycle in tissues and body
      fluids from mice with myocardial infarction.
AB  - Oxidative stress is suggested to play an important role in several
      pathophysiological conditions. A recent study showed that decreasing 5-oxoproline
      (pyroglutamate) concentration, an important mediator of oxidative stress, by over
      expressing 5-oxoprolinase, improves cardiac function post-myocardial infarction
      in mice. The aim of the current study is to gain a better understanding of the
      role of the glutathione cycle in a mouse model of myocardial infarction by
      establishing quantitative relationships between key components of this cycle. We
      developed and validated an LC-MS method to quantify 5-oxoproline, L-glutamate,
      reduced glutathione (GSH) and oxidized GSH (GSSG) in different biological samples
      (heart, kidney, liver, plasma, and urine) of mice with and without myocardial
      infarction. 5-oxoproline concentration was elevated in all biological samples
      from mice with myocardial infarction. The ratio of GSH/GSSG was significantly
      decreased in cardiac tissue, but not in the other tissues/body fluids. This
      emphasizes the role of 5-oxoproline as an inducer of oxidative stress related to
      myocardial infarction and as a possible biomarker. An increase in the level of 5
      oxoproline is associated with a decrease in the GSH/GSSG ratio, a well
      established marker for oxidative stress, in cardiac tissue post-myocardial
      infarction. This suggests that 5-oxoproline may serve as an easily measurable
      marker for oxidative stress resulting from cardiac injury. Our findings show
      further that liver and kidneys have more capacity to cope with oxidative stress
      conditions in comparison to the heart, since the GSH/GSSG ratio is not affected
      in these organs despite a significant increase in 5-oxoproline.

PMID- 30114607
TI  - Evaluation of extraction and normalisation strategies for the analysis of lipids
      in placental vessels.
AB  - The analysis of lipids in tough or fibrous biological tissues can be challenging
      due to difficulties in obtaining a representative sample following homogenisation
      of the tissue. Furthermore, the choice of normalisation method can have a major
      effect on the quality of quantitative results. Therefore, a range of mechanical
      homogenisation techniques and normalisation strategies were evaluated for
      application to human placental vessels. The findings showed that rotor-stator
      homogenisation in a suitable solvent and wet weight normalisation were the best
      combination of procedures for quantitative analysis of lipids in placental blood
      vessels.

PMID- 30114608
TI  - The application of on-line two-dimensional liquid chromatography (2DLC) in the
      chemical analysis of herbal medicines.
AB  - Herbal medicines are complicated chemical systems containing hundreds of small
      molecules of various polarities, structural types, and contents. Thus far, the
      chromatographic separation of herbal extracts is still a big challenge. Two
      dimensional liquid chromatography (2DLC) has become an attractive separation tool
      in the past few years. Particularly, a lot of attention has been paid to on-line
      2DLC. In this review, we aim to give an overview on applications of on-line 2DLC
      in the chemical analysis of herbal medicines since 2010. Firstly, classification
      and general configurations of on-line 2DLC were briefly introduced. Then, we
      summarized main applications in herbal medicines of heart-cutting 2DLC (LC-LC),
      comprehensive 2DLC (LC * LC), and their combinations, with emphasis on LC * LC.
      Mass spectrometry is the most popular detector coupled with 2DLC, which allows
      sensitive and accurate structural characterization of herbal compounds. Finally,
      future developments in on-line 2DLC techniques were also discussed.

PMID- 30114609
TI  - Combing metabolomics with bioanalysis methods to study the antitumor mechanism of
      the new acridone derivative 8q on CCRF-CEM cells: 8q induced mitochondrial
      mediated apoptosis and targeted the PI3K/AKT/FOXO1 pathway.
AB  - A novel acridone derivative, N-(2-(dimethylamino)ethyl)-1-((3
      methoxybenzyl)amino)-5- nitro-9-oxo-9,10-dihydro-acridine-4-carboxamide (8q),
      which was synthesized in our lab, showed potent anti-leukaemia activity against
      CCRF-CEM cells. Moreover, in silico predictions showed that 8q conformed to the
      rule of five and displayed low toxicity. However, the mechanism of anti-leukaemia
      action remains unclear. The aim of this research was to reveal the probable anti
      leukaemia mechanism of 8q on CCRF-CEM cells. Flow cytometry assay demonstrated
      that 8q induced apoptosis. The expression of caspase family proteins results
      showed that 8q could only promote cleaved caspase-3, 7 and 9 expressions without
      affecting cleaved caspase-8 protein, hinting that 8q induced mitochondrial
      mediated apoptosis. Further, we detected 3 indicators of mitochondrial lesions,
      including increased of Cyt-C release, with a decrease in MMP and ATP levels.
      Next, metabolomics were introduced to assist in the research of the anti
      leukaemia mechanism of 8q. The metabolomics results showed that 100 nM 8q could
      increase the level of GSH, and decrease its oxidation products. These indicated
      8q could influence the ROS, which derived by mitochondria. Then we examined the
      effect of 8q on intracellular ROS levels. What is particularly interesting is
      that 8q inhibited cell ROS stress at low concentration and stimulated ROS stress
      at high concentration. The pro-apoptosis mechanisms of 8q were then explored. 8q
      significantly decreased anti-apoptotic proteins Bcl-2 and Bcl-xL expression,
      whereas it up-regulated the pro-apoptotic proteins Bax, Bak, Bad, Bik and Puma
      expression. In addition, 8q dramatically inhibited the expression of FASN, which
      is related to fatty acid metabolism. Furthermore, PI3K, AKT and FOXO1 were
      inactivated, and the expression of total AKT was also inhibited by 8q treatment,
      which promoted intrinsic apoptosis. In conclusion, these findings demonstrate
      that 8q can induce mitochondrial lesions and promote mitochondrial-mediated
      pathway apoptosis by regulating the expression of Bcl-2 family proteins and
      inhibiting the activity of the PI3K/AKT/FOXO1 signaling pathway.

PMID- 30114610
TI  - Rapid authentication and differentiation of herbal medicine using 1H NMR
      fingerprints coupled with chemometrics.
AB  - The public concern and increasing awareness of herbal medicines calls for methods
      available to assure quality and authenticity. In the present study, a novel
      strategy combing 1H nuclear magnetic resonance (1H NMR) spectral analyses coupled
      with chemometrics was developed and validated to allow comprehensive analysis and
      rapid authentication of herbal medicines. Polygoni Multiflori Radix, a widely
      used herbal medicine and a kind of popular functional food, was taken as an
      example. Characteristic profiling of 1H NMR fingerprints was achieved by genetic
      algorithm and a counter-propagation artificial neural network. Multivariate
      classification methods were employed to evaluate and validate the performance of
      the developed characteristic profiling of 1H NMR fingerprints. The results well
      showed that the proposed method improved the predictive ability of the PLS-DA,
      and presented equivalent performance to the original spectrum in other
      classification methods. In conclusion, the developed method is an accurate,
      sensitive and rapid authentication of Polygoni Multiflori Radix, which could be a
      useful tool for rapid authentication and quality control of herbal medicines.

PMID- 30114611
TI  - Simultaneous determination of alkaloids dicentrine and sinomenine in Stephania
      epigeae by 1H NMR spectroscopy.
AB  - Stephania epigaea Lo is an important herbal medicine used as antiphlogistic and
      analgesic drugs. Its major components are dicentrine (1) and sinomenine (2). In
      the present study, a rapid, accurate, and precise method for simultaneous
      quantitation of dicentrine (1) and sinomenine (2) in S. epigeae using 1H NMR
      spectra was developed. The deuterated solvent of DMSO-d6 enabled satisfactory
      separation of the signals to be integrated in 1H NMR spectrum and dimethyl
      terephthalate was selected as an internal standard. The feature signals of delta
      7.57 and 5.70 were selected for quantifying the dicentrine (1) and sinomenine
      (2), respectively. Validation of the quantitative method was performed in terms
      of specificity, accuracy, precision, and stability. This work implied that
      quantitative 1H NMR represents a feasible alternative to high-performance liquid
      chromatography-based methods for quantitation of dicentrine (1) and sinomenine
      (2) in S. epigeae and is suitable for the quality control of S. epigeae.

PMID- 30114612
TI  - Simultaneous optimization of mobile phase composition and pH using retention
      modeling and experimental design.
AB  - Chromatographic methods are progressing continuously. Increasing sample
      complexity and safety expectations lead to higher regulatory demands, hence
      challenges in liquid chromatography analysis are rising, even today, when faster
      and faster chromatographic systems are extensively employed and become widely
      accessible for successful method development. The goal of this study was to
      investigate the impact of mobile phase influences as important factors of
      selectivity tuning in method development. This would mitigate mobile phase
      related robustness issues throughout the method's lifecycle. To discover and
      understand these effects, a new module of chromatographic modeling software
      DryLab (ver. 4.3.4. beta) was introduced and a special experimental design (DoE)
      was tested, allowing the simultaneous optimization of solvent-dependent
      parameters, such as gradient time (tG), ternary eluent composition (tC) and pH,
      requiring 18 input experiments (2 * 3 * 3 = 18). Additionally, the model
      creation, using a UPLC system and a narrow bore column (50 * 2.1 mm), the entire
      experimental work could be finished in 2-3 hours. To demonstrate the
      applicability of this new design, amlodipine and its related pharmacopoeia
      impurities (A-H) were subjected to be used in a case study. Predicted vs.
      Experimental (or Verification) runs showed excellent agreement, average retention
      time deviations were typically less than 1 s. Modelled robustness testing was
      also performed, elucidating all important mobile phase and instrument parameters
      that could influence a method's lifetime performance. Furthermore, as the in
      silico robustness testing is the least time consuming part of the method
      development process, it can be used extensively to evaluate robustness even at
      the very early part in stage 1 of the Method Life Cycle (MLC).

PMID- 30114613
TI  - Proteomic analysis of evodiamine-induced cytotoxicity in thyroid cancer cells.
AB  - Evodiamine is a natural product extracted from herbal plants such as Tetradium
      which has shown to have anti-fat uptake and anti-proliferation properties.
      However, the effects of evodiamine on the behavior of thyroid cancers are largely
      unknown. To determine if evodiamine might be useful in the treatment of thyroid
      cancer and its cytotoxic mechanism, we analyzed the impact of evodiamine
      treatment on differential protein expression in human thyroid cancer cell line
      ARO using lysine-labeling two-dimensional difference gel electrophoresis (2D
      DIGE) combined with mass spectrometry (MS). This study demonstrated 77 protein
      features that were significantly changed in protein expression and revealed
      evodiamine-induced cytotoxicity in thyroid cancer cells involves dysregulation of
      protein folding, cytoskeleton, cytoskeleton regulation and transcription control.
      Our work shows that this combined proteomic strategy provides a rapid method to
      study the molecular mechanisms of evodiamine-induced cytotoxicity in thyroid
      cancer cells. The identified targets may be useful for further evaluation as
      potential targets in thyroid cancer therapy.

PMID- 30114614
TI  - Diagnostic absolute configuration determination of clavulanate potassium: A
      comprehensive investigation of chiroptical spectroscopies and theoretical
      calculations.
AB  - Clavulanate potassium (CP) is a classic beta-lactamase inhibitor, which is
      extensively used as a combination drug in antibiotics therapy. As a chiral drug,
      CP is the only effective stereoisomer revealing prominent activities. To
      determine the chirality of CP efficiently, we provide an accurate and convenient
      method based on the comprehensive investigation of circular dichroism spectra and
      theoretical calculations. The results demonstrate two distinguishable cotton
      effects in electronic circular dichroism (ECD) and a sequence of cotton effect
      signs at specific wavenumbers in vibrational circular dichroism (VCD) can be
      regarded as diagnostic characteristics for the determination of absolute
      configuration. Additionally, the corresponding spectroscopic appearance of CP was
      elucidated with the help of theoretical analysis of molecular orbitals, natural
      bond orbitals and molecular electrostatic potential. The explicit absolute
      configuration determination of CP facilitates the thorough understanding in the
      stereochemistry of clavulanate potassium and its derivatives.

PMID- 30114615
TI  - Does a facilitated pathway improve access to dental services for homeless and
      disadvantaged adults?
AB  - Access to dental care is poorer for people experiencing homelessness and
      disadvantage due to barriers such as lengthy waiting lists, lack of transport,
      lack of information and fear of authorities and treatment. This study aimed to
      evaluate a system integration model for oral health care for clients of homeless
      services in Brisbane, Australia. This model aimed to provide a facilitated access
      pathway between homeless community organisations and a public dental service to
      improve access to dental care. Participants were adult (>=18 years) clients
      Brisbane homeless community organisations. Those who participated in the
      intervention evaluation completed a questionnaire, had their oral health screened
      and followed up for feedback at their dental appointment. Seventy-six clients of
      community organisations in Brisbane participated in the intervention and its
      evaluation. Fear was a barrier to accessing dental services for 23% (n = 18).
      Attendance to the subsequent appointments at the public dental clinic was high,
      with 85% (n = 64) attending their first appointment. A higher proportion of
      participants who had surgical and prosthodontic treatment needs at the screening
      did not attend their appointment compared to those with other needs. Overall the
      model piloted in this study had positive outcomes; with high attendance rates to
      the dental facility and positive experiences by participants.

PMID- 30114616
TI  - Comparative analysis of the factors contributing to sustainability of a food and
      nutrition intervention programme: Two case studies from South Africa.
AB  - Sustainability of health interventions is a consistent and ongoing issue in
      Africa. Understanding key aspects of sustainable interventions provides the
      necessary methods for success. This research evaluates a nutrition intervention
      implemented in two peri-urban communities in the Free State and Gauteng province
      in South Africa (SA) respectively. A case study approach was employed using cross
      case study analyses, including triangular data collection (empirical research
      through surveys of respondents; qualitative data collection through researcher
      journals, diaries, communications and photographs; and research team
      reflections). The information from these case studies is organized according to a
      framework from the United States (US) Office of Organizational Health (OAH) to
      evaluate the sustainability of intervention programmes. All eight of the OAH
      criteria were met in the Free State community and supported the importance of
      these key factors for sustainability compared to only three in the Gauteng
      community. The OAH framework provided a compelling rationale for the relative
      success of the intervention and clearly showed the Free State project was
      sustainable. The Gauteng project was not sustainable. Planned interventions
      should devote significant effort and time towards ensuring sustainability. The
      OAH guidelines provide key steps that the research shows is relevant to the South
      African context.

PMID- 30114617
TI  - Mobile underwater in situ gamma-ray spectroscopy to localize groundwater
      emanation from pockmarks in the Eckernforde bay, Germany.
AB  - Eckernforde Bay in the Baltic Sea is well-known for the pockmarks areas which are
      located in the centre and off the southern shore-line of the bay emanating
      groundwater in a non-continuous but episodic way. Mobile underwater in situ gamma
      ray spectroscopy is exploited proving that both 214Bi and 40K are efficient
      radiotracers for localization of seepage areas whenever either sediment is in
      mixture with the emanating fluid or resuspension of surface sediment occurs as a
      side effect of the fluid emanation.

PMID- 30114618
TI  - Assessment of anthropogenic and geogenic impacts on marine sediments along the
      coastal areas of Egyptian Red Sea.
AB  - The present study was conducted to assess the possible impacts of human
      activities and naturally occurring on the marine sediments, to test for anomalous
      enrichments in metals. A total of 32 marine sediments samples collected from 12
      coastal areas of the Egyptian Red Sea analyzed using different analytical
      techniques. The analysis explored 43 elements for the marine sediments. Principal
      component analysis and multivariate statistics were implemented on the data. The
      extent of pollution was quantified for selected 6 pollutants using the
      geoaccumulation indices (Igeo), enrichment factor (EF), metal pollution index
      (MPI), contamination factor (Cf), and degree of contamination factor (Cd). The
      associated risk using potential ecological risk factor (PER), and risk index (RI)
      was calculated. The data was interpolated using ArcGIS technology to construct
      the spatial distribution maps of the selected 6 pollutants along the coastal
      areas of the Egyptian Red Sea. The data was normalized and the peak values were
      observed for Ca (13.6%) >Na (1.9%) > Mg (1.6%) >Br (41.1 ppm). The obtained
      findings were compared with other local and regional data shows that the metal
      enrichment in studied areas is in line and anomalous enrichments in metals were
      not evidenced. Even though out of 12 studied areas 2 areas viz., Sharam El-Bahari
      in the middle of the coast and downwards to the southern Marsa Hemira area found
      to have peak values of metals, however still show a good agreement with results
      with other data. Moderate enriched sediments with Cr were noticed. It could be
      stated that comparison of the gained data from this study with others clearly
      indicates that nearly the metal concentrations were in the natural unpolluted
      sediments range.

PMID- 30114619
TI  - TIPE2 sensitizes osteosarcoma cells to cis-platin by down-regulating MDR1 via the
      TAK1- NF-kappaB and - AP-1 pathways.
AB  - TIPE2 participates in multiple types of cancer development. However, its
      mechanism underlying chemoresistance in osteosarcoma has not been elucidated.
      Herein, we observed the expression of TIPE2 and MDR1 in cis-platin-resistant
      osteosarcoma tissues and cell lines. Compared to their matched sensitive cell
      lines and tissues, TIPE2 was downregulated while MDR1 expression was increased.
      Further investigation showed that overexpression of TIPE2 effectively inhibited
      MDR1 expression and greatly sensitized osteosarcoma cells to cis-platin, both in
      vivo and in vitro. Mechanistically, TIPE2 inhibited the transcription of the MDR1
      promoter by interfering with the TAK1-NF-kappaB and -AP-1 pathways. Overall, our
      results elucidated for the first time that TIPE2 sensitizes osteosarcoma cells to
      cis-platin through downregulation of MDR1 and may be a novel target in
      osteosarcoma therapy.

PMID- 30114620
TI  - Modelling the dispersion of radon-222 from a landform covered by low uranium
      grade waste rock.
AB  - The dispersion of 222Rn from the planned remediation of the Ranger U mine in the
      wet-dry tropics of Northern Australia was modelled. Dry and wet season contour
      maps of 222Rn dose normalised to 226Ra activity concentration in the proposed
      waste rock substrate on the remediated landform were developed. Three example
      exposure scenarios were assessed based on an anticipated waste rock 226Ra
      activity concentration of 800 Bq kg-1. The estimated above-background annual dose
      from 222Rn to hypothetical receptors at the Aboriginal community at Mudginberri
      (~10 km NNW) was 0.005 mSv and at the township of Jabiru (~7 km W) was 0.033 mSv.
      The estimated above-background annual dose for the hypothetical worst case
      scenario, representing a receptor 1 km WNW of the landform centroid during the
      dry season and at the centroid during the wet season, was 0.13 mSv. Variability
      analysis on the 20 y meteorological dataset used in the dispersion modelling
      showed that the dry and wet season 222Rn dose predictions in any single year
      could be approximately double those of an average year, which suggests that
      estimates of average 222Rn dose should potentially be doubled if the assessment
      aim is to demonstrate compliance with the public dose limit.

PMID- 30114621
TI  - Removal capacity and chemical speciation of groundwater iodide (I-) and iodate
      (IO3-) sequestered by organoclays and granular activated carbon.
AB  - Radioiodine (present mostly as 129I) is difficult to remove from waste streams or
      contaminated groundwater because it tends to exist as multiple anionic species
      (i.e., iodide (I-), iodate (IO3-) and organo-iodide) that do not bind to minerals
      or synthetic materials. In this work, the efficacy of organoclay OCB and OCM, and
      granular activated carbon (GAC) as sorbents to bind I- and IO3- from artificial
      groundwater (AGW) was examined. These sorbents were highly effective at removing
      I- and IO3- from AGW under oxic condition, with the adsorption capacity up to 30
      mg I/g sorbent. Based on X-ray spectroscopy measurements, I- was bound to organic
      ligands in organoclays OCB and OCM, but when GAC was exposed to I- in
      groundwater, the sequestered I species was molecular I2. For IO3- interacting
      with organoclay OCB and GAC, the adsorbed I species remained being IO3-, but when
      organoclay OCM that contains both quaternary amine and sulfur was exposed to IO3
      , the sulfur compound would reduce IO3- to I- that was then bound to organic
      ligands. Thus, the inexpensive and high-capacity organoclays and GAC may provide
      a practical solution for removing 129I contaminant from environmental systems and
      liquid nuclear wastes.

PMID- 30114622
TI  - Sorption of 137Cs, 90Sr, Se, 99Tc, 152(154)Eu, 239(240)Pu on fractured rocks of
      the Yeniseysky site (Nizhne-Kansky massif, Krasnoyarsk region, Russia).
AB  - The study demonstrates the effect of sorption properties of fractured host rocks
      from the Yeniseysky site (Nizhne-Kansky rock massif, Krasnoyarsk region) on the
      migration of dissolved radioactive components (137Cs, 90Sr, 79Se, 99Tc,
      152(154)Eu, 239(240)Pu) in the deep geological conditions of a high-level
      radioactive waste repository. Estimates of radionuclide distribution coefficients
      between the aqueous solution and fractured rocks obtained from sorption
      experiments were used to study the influence of various petrographic types and
      fracture-filling substances on the retardation of radioactive components by
      different fractured rock units of Nizhne-Kansky rock massif. Based on the results
      of sorption experiments, we concluded that the type and attributes of rock
      discontinuities, as well as the mineral composition of the material in fractures,
      are crucial for the immobilization of radionuclides during their migration
      through a geological environment.

PMID- 30114624
TI  - Spatiotemporal and demographic variation in the association between temperature
      variability and hospitalizations in Brazil during 2000-2015: A nationwide time
      series study.
AB  - BACKGROUND: Extreme temperature events are known to be adversely associated with
      a range of health outcomes, but little is known about the effect of less extreme,
      but more frequent fluctuation in temperature. We examined the spatiotemporal and
      demographic variation in the effect of temperature variability (TV) on nationwide
      hospitalizations in Brazil during 2000-2015. METHODS: Data on daily
      hospitalizations and weather variables were collected from 1814 cities,
      comprising 78.4% of Brazilian population. TV was defined as the standard
      deviation of daily minimum and maximum temperatures during exposure days. City
      specific TV effect was estimated using a quasi-Poisson regression model, and then
      pooled at the national and regional level using meta-analysis. Stratified
      analyses were performed by sex, 10 age-groups, and 11 cause categories. Meta
      regression was applied to city-year-specific estimates to examine the temporal
      change. RESULTS: The estimate of TV effect peaked on 0-1 days' exposure,
      contributing to 3.5% [95% confidence interval (CI): 3.1-3.8%] of hospitalizations
      nationwide, equalling 221 (95%CI: 200-242) cases per 100,000 population annually.
      The effect estimate varied across 11 cause categories, which was strongest for
      respiratory admissions. Males, particular those 10-49 year old were more affected
      than females but there was no sex difference for the attributable hospitalization
      rate. The attributable rate for the under-fives was twice as high as for the
      elderly, and five times higher than in adults. The majority of the most affected
      cities were located in the central west and the inland of northeast. The risk of
      hospitalization related to TV showed a significant increase over the 16-year
      period at the national level. CONCLUSIONS: In Brazil, the effect of TV on
      hospitalization is acute, and varies by spatial, sex, age, and cause category.
      Given there is no evidence regarding TV adaptation, hospitalization burden
      associated with TV is likely to further increase and warrants consideration when
      developing future public health policies in the context of climate change.

PMID- 30114625
TI  - Unexpected high multiple sclerosis activity after switching from fingolimod to
      alemtuzumab.
AB  - Unexpected high disease activity (UHDA) after Fingolimod withdrawal has recently
      become a controversial concern for physicians. Here, we report the case of a
      patient with severe exacerbation of MS after switching from Fingolimod to
      Alemtuzumab treatment. This UHDA despite profound lymphopenia raised the question
      of the management of sequential use of biotherapies such as Fingolimod and
      Alemtuzumab in MS.

PMID- 30114623
TI  - Impacts of farmed fish consumption and food trade on methylmercury exposure in
      China.
AB  - The global pollutant mercury (Hg), especially as methylmercury (MeHg), threatens
      human and ecosystem health. But major contributors of MeHg exposure to people in
      China remain highly debated. We developed the China Mercury Exposure Assessment
      (CMEA) model, which incorporates human exposure pathways for MeHg and total Hg
      (THg), the interregional, including international and interprovincial, food
      trading as well as human physiology to provide a comprehensive system that can
      evaluate the pathway of Hg forms to human consumers in China. Based on the CMEA
      model that employed the most comprehensive and recent data, we have found that
      the Probable Daily Intake (PDI) of MeHg for the Chinese population was 0.057
      (range: 0.036-0.091 as 60% confidence interval) MUg.kg-1.day-1, while that of THg
      was 0.35 (range: 0.22-0.55) MUg.kg-1.day-1. MeHg exposure was dominated by fish
      intake, especially by farm-raised freshwater fish due to higher consumption of
      these fish. In 2011, fish intake contributed to 56% to the total MeHg exposure,
      followed by rice (26%). Consumption of farm-raised fish reduced human exposure to
      MeHg by 33%. On the other hand, interregional food trading increased MeHg
      exposure of the Chinese population, as a whole, by 7.6%. The international and
      interprovincial food trades contributed to 5.1% and 22% of MeHg intake,
      respectively. For the whole China, fish intake related exposure to MeHg was
      highest for the Eastern and Northeastern populations, while Tibetans were
      chronically exposed to the highest MeHg from other sources. Our findings
      highlight the importance of farmed fish and food trade for MeHg exposure.

PMID- 30114626
TI  - Dysregulation of long non-coding RNA profile in peripheral blood of multiple
      sclerosis patients.
AB  - Multiple sclerosis (MS) is a chronic autoimmune disorder in which dysregulation
      or aberrant expressions of several immune-related genes have been noted. More
      recently, the participation of long non-coding RNAs (lncRNAs) in regulation of
      immune responses has been highlighted. In the present study, we evaluated
      expression levels of three lncRNAs named Nuclear Paraspeckle Assembly Transcript
      1 (NEAT1), P21 associated ncRNA DNA damage activated (PANDA) and Taurine-up
      regulated gene 1 (TUG1) in peripheral blood of 50 relapsing-remitting MS patients
      and 50 matched healthy subjects. All three lncRNAs have been significantly over
      expressed in MS patients compared with healthy subjects. In addition, significant
      correlations were found between expression levels of these three lncRNAs in the
      patients group. NEAT1 expression was inversely correlated with age at onset and
      disease duration in female patients. Moreover, TUG1 expression was inversely
      correlated with disease duration in female patients. The present study provides
      further evidences for the role of lncRNAs in pathogenesis of MS.

PMID- 30114627
TI  - Recipient-derived IL-22 alleviates murine acute graft-versus-host disease in
      association with reduced activation of antigen presenting cells.
AB  - Acute graft-versus-host disease (aGVHD) remains a major challenging complication
      of patients receiving allogeneic hematopoietic cell transplantation (allo-HCT).
      CD4+ effector T cells and their related cytokines mediate pathogenesis of aGVHD,
      in which donor-T-cell derived interleukin-22 (IL-22) was recently indicated to
      play a role. The role of recipient-derived IL-22 in aGVHD remains to be
      elucidated. By applying IL-22 knock out (IL-22KO) mice as recipients of
      allotransplant, we found recipient derived IL-22 alleviated aGVHD and improved
      survival of allotransplant recipients. Knock out of IL-22 in recipient increased
      levels of T-helper (Th1) 1 cells but decreased levels of regulatory T cells
      (Tregs) in target tissues of aGVHD. Levels of IL-22 increased in aGVHD mice.
      Recipient antigen presenting cells (APCs) are important sources of IL-22. IL-22
      reduced activation of APCs in vitro. Defect of IL-22 in APCs resulted in
      increased polarization of Th1 cells but decreased level of Tregs in an in vitro
      co-culture system. Our data highlight an immunoregulatory function of recipient
      derived IL-22 in aGVHD.

PMID- 30114629
TI  - Effects of fish oil-based lipid emulsion on inflammation and kidney injury in
      mice subjected to unilateral hind limb ischemia/reperfusion.
AB  - This study investigated the effects of a fish oil-based lipid emulsion (FO) on
      local skeletal muscle and remote renal damage at 72 h post-reperfusion in a
      murine model of hind limb ischemia-reperfusion (IR) injury. Mice were assigned to
      1 sham group and 3 IR groups. The IR groups were treated daily with either saline
      or FO from 3 days prior to limb ischemia till 3 days after reperfusion. Limb IR
      was induced by applying a 4.5-oz orthodontic rubber band above the left greater
      trochanter for 120 min followed by band-released reperfusion for 72 h. Mice were
      then sacrificed to harvest blood, muscle, and kidney for analysis. The results
      showed that IR injury led to upregulation of pro-inflammatory monocytes in blood,
      infiltration of leukocytes into injured muscle, and over-expression of pro
      inflammatory genes in muscle and kidney tissues. Supplementing FO either before
      or after IR injury alleviated IR-induced inflammatory gene expressions in muscle
      and kidney tissues. Furthermore, FO given after IR injury reduced circulating pro
      inflammatory monocytes, limited muscle leukocytic infiltration, and improved
      renal histology. These results suggest that FO may protect the muscles from IR
      injury. FO given after IR injury can better downregulate the inflammation seen in
      IR-induced remote kidney injury.

PMID- 30114628
TI  - Hyperglycemia induces inflammatory mediators in the human chorionic villous.
AB  - This study was based on the hypothesis that IL-1beta and its central regulator,
      the inflammasome, may play a role in the inflammatory condition exhibited by
      placental tissues from mothers with different gestational hyperglycemia levels.
      Pregnant women were classified according to the glycemic reference as non
      diabetic (n = 15), mild gestational hyperglycemia (n = 15), gestational diabetes
      mellitus (n = 15) and type 2 diabetes mellitus (n = 15). We investigated levels
      of pro-inflammatory factors in maternal plasma and placental tissues (by ELISA or
      immunohistochemistry) and, NFKB activity (by electrophoretic mobility shift
      assay) and inflammasome protein expression (by Western blot) in chorionic
      villous. Maternal plasma and placental levels of inflammatory factors (IL-1beta,
      IL-6, and MCP-1) were increased during all hyperglycemic conditions. Villous
      stroma cells showed strong immunoreactivity to CD68. In addition, with
      syncytiotrophoblast, the villous stroma cells were also stained to detect iNOS,
      MCP-1, TLR2, and TLR4. Although the levels of protein had fluctuated in the
      groups, NLRP1, NLRP3, ASC, and Caspase 1 were up-regulated in all hyperglycemic
      groups suggesting the inflammasome may be assembled in these pregnant women. The
      NFKB activity also exhibited higher levels in hyperglycemic groups, which might
      imply in pro-inflammatory cytokines production. In summary, increased maternal
      glucose levels during pregnancy changed systemic and placental inflammatory
      patterns, which occurred in parallel with the expression of inflammasome factors
      and processing and secretion of the pro-inflammatory cytokine IL-1beta. These
      results suggest an inflammatory condition in all gestational hyperglycemic
      conditions, even in hyperglycemia that is less severe than gestational or overt
      diabetes, likely associated with inflammasome activation and inflammatory
      cytokine secretion. Inflammasome activation as a possible source of inflammatory
      factors may be an important target to be considered while managing hyperglycemia
      and preventing adverse pregnancy outcomes.

PMID- 30114630
TI  - IL-9 receptor: Regulatory role on FLS and pannus formation.
AB  - OBJECTIVE: Functions of the Th9 cells and its signature cytokine IL-9 in human
      autoimmune diseases is currently under extensive research. Here we are reporting
      new functions of IL-9-receptor (IL-9R); its regulatory role on (i) FLS
      (fibroblast like synoviocyte) biology and (ii) pannus formation in rheumatoid
      arthritis (RA) and psoriatic arthritis (PsA). METHODS: RA, PsA, and OA synovial
      tissue biopsies were obtained; FLS were derived and cultured from these tissues.
      T quantify protein and messenger RNA levels of IL9-receptor (IL-9R) Western blot
      and real-time PCR techniques were used. For Pro-growth/survival effect of IL-9
      (rIL-9) Annexin-V (apoptosis assay) and MTT assays were used. RESULTS: Immunoblot
      and RT-PCR studies demonstrated IL9-R in FLS of RA, PsA, and OA. IL9-R was
      functionally active. rIL-9 induced significant proliferation of FLS (p < 0.001)
      and had an inhibitory effect on TNF-alpha induced apoptosis. Proliferation of FLS
      induced by rIL-9 could be significantly inhibited (p < 0.001) with an IL-9R
      antibody. Further we observed, rIL-9 induced increased secretion of IL-6, IL-8
      and also unregulated MMP-3 expression in FLS. CONCLUSIONS: Proliferation of FLS,
      induction of pro-nflammatory cytokines and upregulation of metaloprotinase (MMP
      3) the key pathologic events for pannus formation are regulated by IL-9 and its
      recptor. Thus the IL-9/IL-9R system is a new contributing factor in the cytokine
      network of PsA and RA.

PMID- 30114631
TI  - Risk stratification for colorectal neoplasia detection in the Flemish colorectal
      cancer screening programme.
AB  - BACKGROUND: The quantitative faecal immunochemical test (FIT) detects pre
      cancerous lesions and colorectal cancer (CRC). Current CRC screening programmes
      are based upon a binary FIT result. This study evaluates the possibility of
      personalised risk prediction, based on FIT, age and gender to gain more insight
      into improving discrimination between normal outcomes, pre-cancerous lesions,
      carcinoma in situ and CRC working towards a more tailored screening approach.
      METHODS: In this retrospective study, from October 2013 until July 2016, data
      from 57,421 participants who underwent a colonoscopy after a positive FIT in the
      Flemish CRC screening programme were analysed using a multinomial multivariable
      logistic regression model. RESULTS: A significant difference in risk of detecting
      neoplasia was found between the established risk profiles based on the
      combination of the quantitative FIT, age and gender. The odds for detecting CRC
      in men aged 74, with a FIT result of >=1000 ng/ml, was higher by a factor of
      58.43 than that for women aged 56, with a FIT result of 75 ng/ml. CONCLUSION: A
      large difference in risk with regard to the detection of colorectal neoplasia was
      found, based on demographics of the population. For some participants, the chance
      of finding no anomalies was more than 60%. Including additional variables in a
      prediction model could further increase discrimination between outcomes and
      practicality.

PMID- 30114632
TI  - Wicherhamomyces anomalus biofilm supported on wood husk for chromium wastewater
      treatment.
AB  - A Wickeramomyces anomalus biofilm supported on wood husk was used to remediate
      water bodies contaminated with chromium (Cr), in batch and open systems. The
      favorable adhesion ability of the chromium-resistant yeast strain on the wood
      husk was predicted by XDLVO theory and confirmed by environmental scanning
      electronic microscopy. The chromium decontamination was then optimized in a batch
      mode using a central composite design (CCD). Analysis of variance (ANOVA) showed
      a high coefficient of determination (R2) value of 0.93-0.91 for Cr(VI) and total
      Cr removal, respectively, ensuring a satisfactory fitting of the second-order
      regression model to the experimental data. In batch system, the concentration of
      biomass exhibited the minimal effect on the process. An acidic pH of 3.72 and
      5.48, an initial chromium concentration of 10 and 16.91 mg/L and a support dose
      of 6.95 and 8.20 g/L were optimal for Cr(VI) and total Cr removal, respectively.
      The breakthrough curves were determined in open system for different initial
      chromium concentrations. The study of glucose concentration effect on the yeast
      extracellular polymeric substances (EPS) production showed that a medium exempt
      of glucose allowed maximal EPS production and minimal chromium removal
      efficiency, while 20 g/L glucose concentration of presented the optimal condition
      for chromium removal.

PMID- 30114633
TI  - Inhalational supplementation of metformin butyrate: A strategy for prevention and
      cure of various pulmonary disorders.
AB  - The management of chronic lung diseases such as cancer, asthma, COPD and
      pulmonary hypertension remains unsatisfactory till date, and several strategies
      are being tried to control the same. Metformin, a popular anti-diabetic drug has
      shown promising effects in pre-clinical studies and has been subject to several
      trials in patients with debilitating pulmonary diseases. However, the clinical
      evidence for the use of metformin in these conditions is disappointing. Recent
      observations suggest that metformin use in diabetic patients is associated with
      an increase in butyrate-producing bacteria in the gut microbiome. Butyrate,
      similar to metformin, shows beneficial effects in pathological conditions found
      in pulmonary diseases. Further, the pharmacokinetic data of metformin suggests
      that metformin is predominantly concentrated in the gut, even after absorption.
      Butyrate, on the other hand, has a short half-life and thus oral supplementation
      of butyrate and metformin is unlikely to result in high concentrations of these
      drugs in the lung. In this paper, we review the pre-clinical studies of metformin
      and butyrate pertaining to pathologies commonly encountered in chronic lung
      diseases and underscore the need to administer these drugs directly to the lung
      via the inhalational route.

PMID- 30114634
TI  - Ganoderma lucidum: Persuasive biologically active constituents and their health
      endorsement.
AB  - Ganoderma lucidum comprises probably 400 different biologically active
      constituents principally polysaccharides, triterpenoids, proteins, enzymes,
      steroids, sterols, nucleotides, fatty acids, vitamins and minerals which have
      been proved to have several therapeutical properties to control various diseases.
      Broad spectrum of its pharmacological actions have been established which include
      immunomodulation, anticancer, antidiabetic, antioxidant, antiatherosclerotic,
      antifibrotic, chemopreventive, antitumor, anticancer drug toxicity prevention,
      analgesic, anti inflammatory, antinociceptive, antimicrobial, hypolipidemic,
      hepatoprotective, antiandrogenic, antiangiogenic, antiherpetic, antiarthritic,
      antiosteoporotic, antiaging, antiulcer properties and estrogenic activity. The
      present review is an effort to investigate and compile the reported biologically
      active compounds, pharmacological activity, toxicity and comparative study of
      different medicinal mushrooms.

PMID- 30114635
TI  - Preclinical evaluation of the diuretic and saluretic effects of (-)-epicatechin
      and the result of its combination with standard diuretics.
AB  - Several studies have suggested that (-)-epicatechin-containing foods and plant
      extracts benefit conditions that affect the cardiovascular system, such as
      hypertension and endothelial dysfunction. However, no study was conducted so far
      to evaluate the potential of this flavonoid on diuretic activity assay. For that,
      female Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR)
      received a single oral treatment with (-)-epicatechin (EPI), hydrochlorothiazide
      (HCTZ) or just vehicle (VEH). The effects of EPI in combination with diuretics
      for clinical use, as well as with L-NAME, atropine and indomethacin were also
      explored. Cumulative urine volume, plasma and urinary parameters were evaluated
      at the end of 8 h experiment. When given to NTR and SHR, at doses of 0.3, 1 and 3
      mg/kg, EPI was able to stimulate both diuresis and saluresis (Na+, K+ and Cl-),
      without interfering with plasma electrolyte content or urinary pH and uric acid
      values, when compared with VEH-treated only rats. The combination with HCTZ, but
      not with furosemide or amiloride, successfully strengthened EPI-induced diuresis.
      This effect was not accompanied by a potentiation of the saluretic effects. On
      the other hand, when given EPI in combination with amiloride, a significant
      increase in Cl- excretion and maintenance of the potassium-sparing effects
      characteristic of this class of diuretics were detected. In addition, the
      diuretic effect of EPI was enhanced after pretreatment with L-NAME and its action
      was significantly precluded in the presence of indomethacin, a cyclooxygenase
      inhibitor. In conclusion, this study shows the diuretic and saluretic properties
      of EPI in rats, adding another biological activity whose effect may contribute to
      the different positive actions already described.

PMID- 30114636
TI  - Analgesic effects of TLR4/NF-kappaB signaling pathway inhibition on chronic
      neuropathic pain in rats following chronic constriction injury of the sciatic
      nerve.
AB  - OBJECTIVE: Chronic neuropathic pain (CNP) is attributed to a lesion or disease of
      the somatosensory system, may be derived from the peripheral and central system.
      Recent study revealed that spinal cord stimulation attenuated CNP by inhibiting
      TLR4/NF-kappaB signaling pathway. The present study focuses on the potential
      analgesic effects of TLR4/NF-kappaB signaling pathway on CNP in a rat model of
      chronic constriction injury (CCI). METHODS: We successfully established the rat
      model of CCI by Bennett method, and then inhibited the TLR4/NF-kappaB signaling
      pathway in rat models. Next, we measured the mechanical withdrawal threshold
      (MWT) and thermal withdrawal latency (TWL) 0D, 2D, 6D, 8D and 12D after operation
      respectively. MTS510 100 mg/kg, an inhibitor of TLR4, was intrathecal injected
      into rats after 6D, 8D and 12D after operation. The experiment lasted for 12
      days, and then the rats were sacrificed to collect the spinal cord tissues.
      Protein and mRNA expression levels of toll-like receptor 4 (TLR4), nuclear factor
      kappaB (NF-kappaB), glial cell line-derived neurotrophic factor (GDNF), glial
      fibrillary acidic protein (GFAP) and nerve growth factor (NGF) were detected by
      western blot analysis and RT-qPCR, respectively. Immunohistochemistry was
      performed to detect GDNF, GFAP and NGF expression. RESULTS: With the prolongation
      of MTS510 treatment time, MWT and TWL were increased and finally, the MWT and TWL
      were close to the baseline level. The levels of TLR4, NF-kappaB, GDNF, and GFAP
      as well as NGF increased in rats treated with CCI + Immunoglobulin G1 (IgG1) or
      CCI + MTS510, suggesting the model establishment was successful. Besides, with
      the prolongation of MTS510 treatment time, the protein level and mRNA expression
      of NF-kB, GDNF, GFAP and NGF decreased in rats treated with CCI + IgG1 or CCI +
      MTS510. Moreover, the GDNF, GFAP and NGF expression in spinal cord tissue in rats
      treated with CCI + IgG1 or CCI + MTS510 increased obviously, while the GDNF, GFAP
      and NGF expression decreased in spinal cord tissue in rats treated with CCI +
      IgG1 or CCI + MTS510 after MTS510 treatment. CONCLUSIONS: Collectively, this
      study defines the role of TLR4 and NF-kappaB, and inhibition of TLR4/NF-kappaB
      signaling pathway might contribute to the alleviation of CNP and improvement of
      MWT and TWL in a rat model of CCI. Additionally, the results obtained from the
      study provided a promising basis that could aid as an experimental basis for the
      potential treatment of TLR4/NF-kappaB signaling pathway.

PMID- 30114637
TI  - Safety evaluation, anti-oxidative and anti-inflammatory effects of subchronically
      dietary supplemented high dosing grape seed powder (GSP) to healthy rat.
AB  - Grape seed powder (GSP) contains high amount of bioactive polyphenols usually
      used as nutritional supplement or food preservatives due to their antioxidant and
      scavenging properties. The purpose of the present work was to evaluate the safety
      of increasing dosage GSP (w/w) of 0.5%, 5%, 10% and 20% corresponding to 0.4, 4,
      8 and 16 g/kg bw respectively, when administered sub-chronically to Wistar rats
      in a 2 month-repeated dosing oral toxicity trial. Overally GSP had no effect on
      food intake, decreased body weight gain without affecting brain, liver, heart or
      kidney relative weight. GSP did not alter haematology except an increase in
      platelets, slightly decreased plasma transaminases, creatinine, urea and xanthine
      oxidase activity, without affecting uricemia, glycemia, triglyceridemia and
      cholesterolemia. GSP did not affect intracellular mediators as calcium, free iron
      or H2O2, but exerted real anti-oxidative properties in the four selected organs
      as assessed by lower lipoperoxidation and carbonylation, higher non protein
      thiols and antioxidant enzyme activities as CAT, GPx and SOD. Besides GSP exerted
      anti-inflammatory properties as supported by lower plasma IL17 A and CRP and
      higher IL10 and adiponectin. Histopathologically GSP provoked the dilation of
      heart and kidney arterioles and increased the size of the hippocampal dentate
      gyrus reflecting higher neurogenesis as assessed by Ki-67 labeling. Under the
      experimental conditions of the current study, GSP appeared as highly safe even
      when administered at very high dosage and could find potential applications in a
      variety of biotic or abiotic stresses-induced multi-organ dysfunction.

PMID- 30114638
TI  - Knockdown of lncRNA XIST inhibits retinoblastoma progression by modulating the
      miR-124/STAT3 axis.
AB  - Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) was reportedly
      to be tightly associated with tumorigenesis and progression of multiple cancers.
      However, the expression, biological function, and action mechanisms of XIST in
      retinoblastoma (RB) are still unknown. Here, we found that XIST expression was
      upregulated in RB tissues and cell lines, and that increased XIST expression was
      positively associated with advanced cTNM stage (III-V) and late differentiation
      status. We also revealed that knockdown of XIST inhibited RB cell proliferation,
      promoted cell cycle at G1/G0 phase, and induced cell apoptosis. Mechanistically,
      XIST directly bound to microRNA (miR)-124 in RB cells. XIST mRNA expression was
      inversely correlated with miR-124 in RB tissues. Importantly, miR-124 inhibition
      partially reversed the effect on cell proliferation, cycle arrest and apoptosis
      by XIST knockdown mediated. In addition, XIST could regulate expression of signal
      transducer and activator of transcription 3(STAT3), a directly target of miR-124
      in RB. These findings implied that XIST promoted RB progression partially by
      modulating the miR-124/STAT3 axis.

PMID- 30114639
TI  - Honokiol: An anticancer lignan.
AB  - BACKGROUND: Honokiol ((3',5-di-(2-propenyl)-1,1'-biphenyl-2,2'-diol), a lignan,
      is a promising antitumor compound, having exerted activity against a number of
      human cancer cell lines. Honokiol has inhibitory role on the proliferation,
      invasion and survival of cancer cells in in vitro as well as in vivo studies. It
      interferes with signaling pathways components in order to elicit the anticancer
      effect. SCOPE AND APPROACH: In present review, the published data on the efficacy
      of honokiol against various cancer cell lines and tumor-bearing animal models has
      been presented and discussed. KEY FINDINGS AND CONCLUSIONS: Honokiol lowers the
      expression of pluripotency-factors, the formation of mammosphere, P-glycoprotein
      expression, receptor CXCR4 level, c-FLIP, steroid receptor coactivator-3 (SRC-3),
      Twist1, matrix metalloproteinases, class I histone deacetylases, H3K27
      methyltransferase among numerous other anticancer functions. It increases bone
      morphogenetic protein 7 (BMP7), Bax protein, among others. It does so by
      interfering with the major checkpoints such as nuclear factor kappa B (NF
      kappaB), and activator of transcription 3 (STAT3), mammalian target of rapamycin
      (m-TOR), epidermal growth factor receptor (EGFR), Sonic hedgehog (SHH). It
      promotes the efficacy of several anticancer drugs and radiation tolerance. The
      derivatization of honokiol results in compounds with interesting attributes in
      terms of cancer control. This review will shed light on the scopes and hurdles in
      the relevance of the bioactive lignan honokiol in cancer management.

PMID- 30114641
TI  - Postmenopausal osteoporosis and breast cancer: The biochemical links and
      beneficial effects of functional foods.
AB  - Breast cancer as a multifactorial disease has been classified among the major
      causes of morbidity and mortality in women across the world, with a higher
      prevalence among post-menopausal women. Osteoporosis, a condition characterized
      by altered bone mineralization is also commonly found among post-menopausal
      women. Consequently, post-menopausal women are at risk of morbidity and mortality
      associated with breast cancer and postmenopausal osteoporosis. This may not be
      unconnected to the fact that, there may be existent biochemical links between the
      two mayhems, which might rally round between the cellular and molecular
      connectivity based on the actions and inactions of RANKL, estrogen, free radicals
      induced oxidative stress and metabolic implications of age related obesity among
      others. Cells and tissues including breast and bone are more prone to oxidative
      stress with age, and oxidative stress could alter the activity of key proteins
      and pathways required for protection against breast cancer and osteoporosis. As a
      result, the potentials of antioxidant rich functional foods in preventing,
      managing and possibly treating breast cancer and postmenopausal osteoporosis
      cannot be overemphasised. This review mainly uses ISI, SCOPUS and PubMed indexed
      journals and books containing various experimental reports vacillating from
      humans, animals and in vitro studies in relation to breast cancer and
      postmenopausal osteoporosis, biochemical links and possible beneficial effects of
      functional foods. One distinct feature of the review is that it categorically
      intends to provide a critical appraisal on the said available experimental data
      within the variables of breast cancer and osteoporosis among females vis-a-vis
      the potentials of functional foods.

PMID- 30114640
TI  - Inhibiting of RIPK3 attenuates early brain injury following subarachnoid
      hemorrhage: Possibly through alleviating necroptosis.
AB  - Necroptosis is an inflammatory form of cell death that depends on receptor
      interacting serine-threonine kinase 3 (RIPK3) and mixed lineage kinase domain
      like (MLKL) and displays the morphological characteristics of necrosis. To date,
      it is unclear to what extent necroptosis contributes to subarachnoid hemorrhage
      (SAH) induced brain injury. The present study aimed to investigate the RIPK3
      mediated necroptosis and the effects of the RIPK3 selective inhibitor GSK'872 in
      early brain injury following SAH. After SAH, RIPK3 expression increased as early
      as 6 h and peaked at 72 h. Double immunofluorescence staining revealed that RIPK3
      was mainly located in neurons. Most necrotic cells were neurons, which were
      further confirmed by TEM. Intracerebroventricular injection of GSK'872 (25 mM)
      could attenuate brain edema and improve neurological function following SAH and
      reduce the number of necrotic cells. In addition, GSK'872 could also decrease the
      protein levels of RIPK3 and MLKL, and cytoplasmic translocation and expression of
      HMGB1, an important pro-inflammatory protein. Taken together, the current study
      provides the new evidence that RIPK3-mediated necroptosis is involved in early
      brain injury and GSK'872 decreases the RIPK3-mediated necroptosis and subsequent
      cytoplasmic translocation and expression of HMGB1, as well as ameliorates brain
      edema and neurological deficits.

PMID- 30114642
TI  - Nanomaterial-involved neural stem cell research: Disease treatment, cell
      labeling, and growth regulation.
AB  - Neural stem cells (NSCs) have been widely investigated for their potential in the
      treatment of various diseases and transplantation therapy. However, NSC growth
      regulation, labeling, and its application to disease diagnosis and treatment are
      outstanding challenges. Recently, nanomaterials have shown promise for various
      applications including genetic modification, imaging, and controlled drug
      release. Here we summarize the recent progress in the use of nanomaterials in
      combination with NSCs for disease treatment and diagnosis, cell labeling, and NSC
      growth regulation. The toxicity of nanomaterials to NSCs is also discussed.

PMID- 30114643
TI  - Long non-coding RNA SNHG5 sponges miR-26a to promote the tumorigenesis of
      osteosarcoma by targeting ROCK1.
AB  - BACKGROUND: Osteosarcoma (OS) is one of the most common invasive malignancies of
      the bone. The long non-coding RNA (lncRNA) SNHG5 (small nucleolar RNA host gene
      5) has been consistently shown to be involved in many cancers, although its
      precise function in osteosarcoma remains poorly understood. In this study, we
      investigated the role of SNHG5 in OS progression and the underlying mechanism.
      METHODS: SNHG5 expression in 32 OS tissues and 4 OS cell lines was measured by
      quantitative real-time PCR (qRT-PCR). Migration, invasion, proliferation and cell
      cycle profiles were analyzed by established assays to determine the biological
      functions of SNHG5 and miR-26a in OS cells. The binding sites of miR-26a in SNHG5
      and ROCK1 were predicted by the RNAhybrid 2.2 program. Luciferase reporter assay
      was then used to validate the direct targeting of SNHG5 with miR-26a and of Rho
      associated coiled coil-containing protein kinase 1 (ROCK1) with miR-26a. The
      effect of SNHG5 on the ROCK signaling pathway was assessed by western blotting.
      RESULTS: Elevated expression of SNHG5 was correlated with poor clinical outcome
      and prognosis in OS patients. SNHG5 functioned as a sponge for miR-26a and
      promoted proliferation, invasion and migration, and accelerated G1 to S phase
      transition in OS cells. SNHG5 functioned as a competing endogenous RNA (ceRNA)
      for miR-26a and activated the ROCK signaling pathway through the miR-26a-ROCK1
      axis. CONCLUSION: SNHG5 acts as an oncogene in OS via the SNHG5-miR-26a-ROCK1
      axis and is therefore a potential novel therapeutic target for OS treatment.

PMID- 30114644
TI  - Upregulation of EID3 sensitizes breast cancer cells to ionizing radiation-induced
      cellular senescence.
AB  - Previous studies have shown that BMS-345541 (BMS, a specific IkappaB kinase beta
      inhibitor) sensitized various tumor cells including MCF-7 breast cancer cells to
      ionizing radiation (IR). However, the mechanisms of BMS action are unknown. Since
      the expression of E1A-like inhibitor of differentiation 3 (EID3) was highly
      upregulated in MCF-7 cells after BMS treatment, we investigated the role of EID3
      in the response of MCF-7 cells to IR. We found that BMS induced EID3 expression
      in MCF-7 cells in a time- and dose-dependent manner. Knockdown of EID3 by
      specific shRNA attenuated BMS-induced radiosensitization in MCF-7 cells. In
      contrast, induction of EID3 expression in an inducible EID3 expressing MCF-7 cell
      line with doxycycline sensitized the cells to IR. EID3-mediated sensitization of
      MCF-7 cells to IR was not attributed to an increase in apoptosis. Instead, EID3
      expressing MCF-7 cells exhibited significantly higher levels of senescence
      associated beta-galactosidase (SA-beta-gal) activity and higher levels of p21 and
      p57 than EID3-MCF-7 cells without induction of EID3 after exposure to IR. Similar
      findings were observed when EID3-expressing MCF-7 cells were treated with
      etoposide, a topoisomerase II inhibitor. Taken together, our findings reveal a
      novel function of EID3 and suggest that the induction of EID3 by BMS may be
      exploited as a new strategy to sensitize breast cancer cells to IR and
      chemotherapy by inducing cancer cell senescence.

PMID- 30114645
TI  - Lycorine: A prospective natural lead for anticancer drug discovery.
AB  - Nature is the most abundant source for novel drug discovery. Lycorine is a
      natural alkaloid with immense therapeutic potential. Lycorine is active in a very
      low concentration and with high specificity against a number of cancers both in
      vivo and in vitro and against various drug-resistant cancer cells. This review
      summarized the therapeutic effect and the anticancer mechanisms of lycorine. At
      the same time, we have discussed the pharmacology and comparative structure
      activity relationship for the anticancer activity of this compound. The
      researches outlined in this paper serve as a foundation to explain lycorine as an
      important lead compound for new generation anticancer drug design and provide the
      principle for the development of biological strategies to utilize lycorine in the
      treatment of cancers.

PMID- 30114646
TI  - Hollow Ag44Pt56 nanotube bundles with high electrocatalytic performances for
      hydrogen evolution and ethylene glycol oxidation reactions.
AB  - It is a main challenge to synthesize highly efficient and durable nanocatalysts
      towards hydrogen evolution reaction (HER) and alcohol oxidation reaction in
      energy conversion and storage. Herein, a green wet-chemical approach was
      developed to directly prepare hollow Ag44Pt56 nanotube bundles (H-Ag44Pt56 NTBs),
      utilizing 5-azacytosine as a structure-directing agent. The obtained
      electrocatalyst displayed superior catalytic activity and durability for HER in
      acid media, and the great improvement in catalytic performance for ethylene
      glycol oxidation reaction (EGOR) in the alkaline electrolyte, outperforming home
      made Ag34Pt66 nanoparticles (NPs), Ag70Pt30 NPs, and commercial Pt/C catalysts.
      The high electrocatalytic characters are mainly attributed to the special
      nanostructures and the synergetic effects between the bimetals.

PMID- 30114647
TI  - Roles of cobalt and cerium species in three-dimensionally ordered macroporous
      CoxCe1-xOdelta catalysts for the catalytic oxidation of diesel soot.
AB  - Three-dimensionally ordered macroporous (3DOM) CoxCe1-xOdelta oxides with
      different Co/Ce atomic ratios were synthesized by a colloidal crystal template
      (CCT) method. They show higher activity for soot combustion in O2 than single
      CeO2 and Co3O4 under loose contact conditions. XRD, Raman, XPS, H2-TPR and soot
      TPR characterizations were carried out to study the surface and bulk oxygen
      vacancies and to correlate them to the activity. There exists electron transfer
      from Ce to Co in the matrix. Both Ce3+ and Co2+ species contribute importantly to
      the creation of surface and bulk oxygen vacancies, which determine the ignition
      and burnout temperatures of the catalysts, respectively.

PMID- 30114648
TI  - 2D-NLDFT adsorption models for porous oxides with corrugated cylindrical pores.
AB  - In this work, we develop two-dimensional models based on the non-local density
      functional theory (2D-NLDFT) for the analysis of pore size distribution (PSD) of
      oxide materials with cylindrical pores with rough and heterogeneous walls. The
      existing standard NLDFT models for porous oxides assume the smooth energetically
      uniform surface of the pore walls. Due to this assumption, the calculated
      theoretical isotherms show typical layering transitions, which are not consistent
      with the experimental adsorption isotherms measured on real oxide materials. As a
      result, the fits of standard NLDFT models to N2 or Ar adsorption isotherms show
      deviations from the experimental points in association with artifacts observed on
      the calculated PSD plots. The 2D-NLDFT framework allows us to improve the
      standard model by introducing the corrugation and energetic heterogeneity to the
      surface of cylindrical pores. The surface roughness and energetic heterogeneity
      are known characteristics of the oxide surfaces. With these assumptions we
      develop a comprehensive approach in which both branches of the adsorption
      isotherm may be used for the PSD analysis of mesoporous oxide materials. We
      validate this approach by using Ar data measured at 87 K on the reference set of
      MCM-41 silica samples (Kruk and Jaroniec, 2000). The generated kernels are
      smooth, do not show layering transitions and fit accurately the reference data.

PMID- 30114649
TI  - The selectively fluorescent sensing detection and adsorptive removal of Pb2+ with
      a stable [delta-Mo8O26]-based hybrid.
AB  - A polyoxomolybdate based hybrid, [delta-Mo8O26](L)2.2H2O (BUC-77), was
      synthesized via hydrothermal method, which exhibited selectively fluorescent
      detection and efficient adsorptive removal toward Pb2+ in aqueous environment. A
      good linearity was observed between the fluorescence quenching percentage of BUC
      77 and the Pb2+ concentration, along with the detection limit being 6.91 ppb. BUC
      77 was stable in common solvents and wide pH range, which could be regenerated by
      being washed with dilute inorganic acids like HNO3 after adsorption of Pb2+. The
      results revealed that BUC-77 could be potentially used to achieve both detection
      and removal of Pb2+ in wastewater.

PMID- 30114650
TI  - Adhesive forces between two cleaved calcite surfaces in NaCl solutions: The
      importance of ionic strength and normal loading.
AB  - The mechanical strength of calcite bearing rocks is influenced by pore fluid
      chemistry due to the variation in nano-scale surface forces acting at the grain
      contacts or close to the fracture tips. The adhesion of two contacting surfaces,
      which affects the macroscopic strength of the material, is not only influenced by
      the fluid chemistry but also by the surface topography. In this paper, we use
      Atomic Force Microscope (AFM) to measure the interfacial forces between two
      freshly cleaved calcite surfaces in CaCO3-saturated solutions with varying NaCl
      concentration. We show that calcite contacts become stronger with increasing NaCl
      concentration (>100 mM), as a result of progressively weaker secondary hydration
      and increasing attraction due to instantaneous ion-ion correlation. Moreover, we
      discuss the effect of normal applied force (Fn) and surface roughness on the
      measured adhesion forces (Fad). We show that the measured pull-off force
      (adhesion) is linearly correlated with the magnitude of Fn, where an increase in
      applied force results in increased adhesion. This is attributed to a larger
      number of contacting surface asperities and thus increase in real contact area
      and the contact-bond strength. We discuss that the possible variation in local
      topography at contacts, together with strong dependence on ionic strength of the
      solution, can explain the inconsistent behavior of calcite rocks in NaCl
      solutions.

PMID- 30114651
TI  - Micro-tomographic analyses of specific interfacial area inside unconsolidated
      porous media with differing particle characteristics from microscopic to
      macroscopic scale.
AB  - HYPOTHESIS: In capillary trapping in an unconsolidated porous medium, the
      interphase area is influenced by the distribution of the trapped phase clusters.
      These attributes, in turn, are affected by particle characteristics, indicating
      that the interphase area is affected by the particle characteristics.
      EXPERIMENTS: A micro-tomography technique was used to observe capillary trapping
      of a nitrogen-water system. The effect of particle characteristics on micro- to
      macroscopic properties was measured, respectively: pore size distribution (PSD)
      and porosity, bubble size distribution (BSD) and saturation, and bubble surface
      area and specific interfacial area. Capillary trapping experiments were carried
      out for media consisting of different particle shapes, range of sizes, and
      degrees of uniformity. FINDINGS: Particle characteristics govern not only the PSD
      but also the pore shape. Then, the PSD and pore shape govern the BSD and bubble
      surface area, thus, affecting the specific interfacial area. The specific
      interfacial area of highly angular particles differs from that of highly
      spherical particles and natural sands. On the basis of these findings, a
      statistical model of PSD and a bubble morphology model are developed. Comparisons
      of specific interfacial area with uniform bubble distribution and thermodynamic
      filling assumption models show that those assumptions predict interfacial area
      less accurately.

PMID- 30114652
TI  - In situ growth of self-supported and defect-engineered carbon nanotube networks
      on 316L stainless steel as binder-free supercapacitors.
AB  - Self-supported and defect-engineered carbon nanotube networks directly grown on
      316L stainless steel are used for binder-free supercapacitors. In situ growth of
      the carbon nanotube networks on 316L stainless steel is obtained through the
      chemical vaporization deposition and thermal treatment to generate various
      defects. The relationship between the microstructures of carbon nanotube networks
      and electrochemical characteristics is investigated. The as-prepared carbon
      nanotube networks are characterized by scanning electron microscopy, transmission
      electron microscopy, X-ray photoelectron spectroscopy and Raman analysis. Cyclic
      voltammetry, galvanostatic charge-discharge and electrochemical impedance
      spectroscopy tests are also carried out to evaluate their capacitive properties,
      suggesting that the electrochemical characteristics are significantly affected by
      annealing time. The carbon nanotube networks annealed at 500 0C for 2 h display
      high capacitance of 11 mF cm-2 and excellent cycling lifetime with capacitance
      retention ration 97% at the scan rate of 0.5 mA cm-2 for 5000 periods, which is
      attributed to the defect engineering increasing the defects of carbon nanotube
      networks, enhancing hydrophilic property and facilitating the transportation of
      electrolyte ions.

PMID- 30114653
TI  - Evidence of photoinduced lipid hydroperoxidation in Langmuir monolayers
      containing Eosin Y.
AB  - Photodynamic therapy (PDT) efficiency depends on many factors including the
      incorporation of the photosensitizer (PS) in cell membranes and possible lipid
      hydroperoxidation. In this study, we show that hydroperoxidation may be
      photoinduced when eosin Y is incorporated into Langmuir monolayers that serve as
      cell membrane models. This occurs for Langmuir monolayers of 1,2-dioleoyl-sn
      glycero-3-phosphocholine (DOPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3
      phosphocholine (POPC), which have unsaturation in their hydrophobic chains. In
      contrast, light irradiation had no effect on monolayers of saturated 1,2
      dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Evidence of hydroperoxidation was
      obtained from the area increase in eosin-containing DOPC and POPC monolayers upon
      irradiation, which was accompanied by a decrease in monolayer thickness according
      to grazing incidence X-ray off-specular scattering (GIXOS) data. Furthermore, the
      changes in polarization-modulated infrared reflection absorption spectroscopy (PM
      IRRAS) induced by irradiation were consistent with hydroperoxide migration toward
      the lipid hydrophilic heads.. In summary, this combination of experimental
      methods allowed us to determine the effects of eosin Y interaction with cell
      membrane models under irradiation, which may be associated with the underlying
      mechanisms of eosin Y as photosensitizer in PDT.

PMID- 30114655
TI  - Social exclusion and cognitive impairment - A triple jeopardy for Chinese rural
      elderly women.
AB  - This study investigates how social exclusion, defined as a multidimensional
      concept encompassing financial deprivation, social isolation, and a lack of basic
      social rights, is associated with cognitive impairment of elderly Chinese. Using
      three waves of the Chinese Longitudinal Healthy Longevity Survey (N = 10,923), we
      find that rural elderly women are the most vulnerable to social exclusion
      (17.28%) and cognitive impairment (18.52%) among the Chinese elderly. After
      addressing the methodological challenges of endogeneity and sample attrition due
      to mortality, and holding an array of demographic, lifestyle, and health
      variables constant, we find that social exclusion is significantly associated
      with higher risks of cognitive impairment. Rural elderly women suffering from
      severe or extreme social exclusion are 23 times more likely to be cognitively
      impaired as compared to their urban male counterparts who are not socially
      excluded. Lack of participation in social activity is the most common risk factor
      associated with cognitive impairment across groups, after controlling for
      relevant covariates.

PMID- 30114654
TI  - Fabrication of dihydroxyflavone-conjugated hyaluronic acid nanogels for targeted
      antitumoral effect.
AB  - We prepared hyaluronic acid (HA)-based nanogels conjugated with dihydroxyflavone
      (DHF) and evaluated their cellular uptake and antitumoral efficiency. 4-(4,6
      dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM) was used as a
      conjugation agent for esterification between DHF and HA as well as crosslinking
      among HA. The conjugations were confirmed by nuclear magnetic resonance
      spectroscopy, UV/vis spectroscopy, and high-performance liquid chromatography.
      The size and Zeta-potential of the DHF/HA nanogels were reduced with an increase
      in the concentration of DMTMM due to the involvement of more HA molecules for the
      conjugation reactions. The DHF/HA nanogel with a smaller size was greatly taken
      up by two kinds of tumor cells (HeLa and HepG2), compared to NIH3T3. The cell
      viabilities were reduced to approximately 60% for HeLa and HepG2 cells after 48 h
      post treatment with DHF/HA nanogels.

PMID- 30114656
TI  - Depression and functioning are important to subjective quality of life after a
      first episode psychosis.
AB  - BACKGROUND: Subjective quality of life (S-QoL) is an important outcome measure in
      first-episode psychosis, but its associations with clinical predictors may vary
      across the illness course. In this study we examine the association pattern,
      including both direct and indirect effects, between specific predefined clinical
      predictors (insight, depression, positive psychotic symptoms and global
      functioning) and S-QoL the first ten years after a first-episode psychosis.
      METHODS: Three hundred and one patients with a first-episode psychosis were
      included at first treatment, and reassessed at 3 months, 1 year, 2 years, 5 years
      and 10 years after inclusion. At 10-year follow-up 186 participated. S-QoL was
      assessed with Lehman's Quality of Life Interview. Applying a structural equation
      model, we investigated cross-sectional association patterns at all assessments
      between the predefined clinical predictors and S-QoL. RESULTS: At baseline, only
      depression was significantly associated with S-QoL. At all follow-up assessments,
      depression and functioning showed significant associations with S-QoL. Insight
      was not associated with S-QoL at any of the assessments. Better insight, less
      depressive symptoms and less positive psychotic symptoms were all associated with
      higher functioning at all assessments. Functioning seems to mediate a smaller
      indirect inverse association between positive psychotic symptoms and S-QoL. The
      association pattern was stable across all follow-up assessments. CONCLUSIONS:
      Together with depression, functioning seems to be important for S-QoL.
      Functioning seems to be a mediating factor between positive symptoms and S-QoL. A
      focus on functional outcome continues to be important.

PMID- 30114657
TI  - Nonsuicidal self-injury, suicide ideation and suicide attempts in the National
      Guard.
AB  - BACKGROUND: Among members of the National Guard, suicide rates are higher than
      age and sex matched civilian counterparts. Across many civilian samples,
      nonsuicidal self-injury has emerged as a particularly strong correlate of suicide
      risk. The current study describes the prevalence and correlates of NSSI and
      suicidal thoughts and behaviors among National Guard members. METHODS:
      Participants were 897 National Guard personnel recruited online who completed
      study measures anonymously. RESULTS: Approximately 6% of males and 14% of females
      reported a history of NSSI. Almost one third of the sample reported suicide
      ideation and 3% of men and 11% of women reported a suicide attempt. NSSI was
      strongly associated with a history of suicide ideation and attempts.
      Characteristics of NSSI were similar across men and women. DISCUSSION: Reliable
      access to effective interventions is essential for National Guard members in
      light of their risk for suicidal and nonsuicidal self-injurious behavior.

PMID- 30114659
TI  - Titanium dioxide nanoparticles induce mouse hippocampal neuron apoptosis via
      oxidative stress- and calcium imbalance-mediated endoplasmic reticulum stress.
AB  - The purpose of this study was to explore the potential neurotoxicity and the
      underlying mechanism of titanium dioxide nanoparticles (TiO2-NPs) to mouse
      hippocampal neuron HT22 cells. We found that TiO2-NPs had concentration-dependent
      and time-dependent cytotoxicities to HT22 cells by the MTT assay. Propidium
      iodide (PI) staining with FACScan flow cytometry proved that TiO2-NPs dose
      dependently increased the apoptosis rate in HT22 cells, and the apoptotic
      features were observed by Hochest 33258 and AO/EB staining. The levels of calcium
      (Ca2+) and reactive oxygen species (ROS) were significantly increased in TiO2-NPs
      treated cells. Further studies by western blot and real-time QPCR proved that the
      protein and mRNA levels of GRP78, IRE-1alpha, ATF6, CHOP and caspase-12 were up
      regulated after TiO2-NPs treatment, which indicates that TiO2-NPs-induced
      cytotoxicity is related to endoplasmic reticulum stress (ERS). Apoptosis-related
      protein cleaved caspase-3 and pro-apoptotic protein Bax expression levels were up
      regulated, and the anti-apoptotic protein Bcl-2 expression level was down
      regulated in TiO2-NPs-treated cells. The antioxidant N-acetyl-L-cysteine (NAC)
      can significantly reduce TiO2-NPs-induced ERS characterized by the down
      regulation of GRP78 and cleaved caspase-12 levels, which indicates that oxidative
      stress is participated in TiO2-NPs-induced ERS. Our study suggests that TiO2-NPs
      induced apoptosis in HT22 cells is through oxidative stress- and calcium
      imbalance-mediated ERS.

PMID- 30114658
TI  - Pharmacogenetic analyses of 2183 patients with advanced colorectal cancer;
      potential role for common dihydropyrimidine dehydrogenase variants in toxicity to
      chemotherapy.
AB  - BACKGROUND: Inherited genetic variants may influence response to, and side
      effects from, chemotherapy. We sought to generate a comprehensive inherited
      pharmacogenetic profile for oxaliplatin and 5FU/capecitabine therapy in advanced
      colorectal cancer (aCRC). METHODS: We analysed more than 200 potentially
      functional, common, inherited variants in genes within the 5FU, capecitabine,
      oxaliplatin and DNA repair pathways, together with four rare dihydropyrimidine
      dehydrogenase (DPYD) variants, in 2183 aCRC patients treated with oxaliplatin
      fluoropyrimidine chemotherapy with, or without, cetuximab (from MRC COIN and COIN
      B trials). Primary end-points were response, any toxicity and peripheral
      neuropathy. We had >85% power to detect odds ratios (ORs) = 1.3 for variants with
      minor allele frequencies >20%. RESULTS: Variants in DNA repair genes (Asn279Ser
      in EXO1 and Arg399Gln in XRCC1) were most associated with response (OR 1.9, 95%
      confidence interval [CI] 1.2-2.9, P = 0.004, and OR 0.7, 95% CI 0.5-0.9, P =
      0.003, respectively). Common variants in DPYD (Cys29Arg and Val732Ile) were most
      associated with toxicity (OR 0.8, 95% CI 0.7-1.0, P = 0.008, and OR 1.6, 95% CI
      1.1-2.1, P = 0.006, respectively). Two rare DPYD variants were associated with
      increased toxicity (Asp949Val with neutropenia, nausea and vomiting, diarrhoea
      and infection; IVS14+1G>A with lethargy, diarrhoea, stomatitis, hand-foot
      syndrome and infection; all ORs > 3). Asp317His in DCLRE1A was most associated
      with peripheral neuropathy (OR 1.3, 95% CI 1.1-1.6, P = 0.003). No common variant
      associations remained significant after Bonferroni correction. CONCLUSIONS: DNA
      repair genes may play a significant role in the pharmacogenetics of aCRC. Our
      data suggest that both common and rare DPYD variants may be associated with
      toxicity to fluoropyrimidine-based chemotherapy.

PMID- 30114660
TI  - Recent advancement of piperidine moiety in treatment of cancer- A review.
AB  - Piperidine is an important pharmacophore, a privileged scaffold and an excellent
      heterocyclic system in the field of drug discovery which provides numerous
      opportunities in studying/exploring this moiety as an anticancer agent by acting
      on various receptors of utmost importance. Cancer is an uncontrolled division of
      cells that results in the formation of tumour which have the potential to migrate
      to other parts of the body (metastasis) finally becoming a major threat to human
      population. Since piperidine displayed great potential in this area it is being
      further probed to get novel entities for the treatment of cancer. This review
      throws light on recent biological expansions of piperidine along with structure
      activity relationships to deliver association between various synthesized
      newer/novel derivatives and receptor sites.

PMID- 30114661
TI  - Pyrrolopyrimidines: An update on recent advancements in their medicinal
      attributes.
AB  - Fused heterocycles are reported to demonstrate variety of biological activities
      such as anticancer, antibacterial, antifungal and anti-inflammatory, and are thus
      exhaustively utilized in the field of medicinal chemistry. Pyrrolopyrimidines is
      one of the major classes of fused heterocycles which are extensively reported
      throughout the literature. Several reports suggest that pyrrolopyrimidine as
      fused scaffold possess more diverse and potent pharmacological profile than
      individual pyrrole and pyrimidine nucleus. Different pathological targets require
      different structural attributes reflected via varied substitutions, thus in
      recent years, researchers have employed various synthetic strategies to achieve
      desired substitutions on the pyrrolopyrimidine nucleus. In this review, authors
      highlight the recent advancement in this area, special focus was laid on the
      pharmacological profile and structure-activity relationship studies (SAR) of
      various synthesized pyrrolopyrimidine derivatives.

PMID- 30114663
TI  - Fasciculation intensity and disease progression in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: To investigate the association between the frequency and intensity of
      fasciculations with clinical measures of disease progression in amyotrophic
      lateral sclerosis (ALS). METHODS: Twenty-four consecutive patients with ALS
      underwent clinical review and neuromuscular ultrasound assessment to detect
      intensity of fasciculations. Results were correlated with clinical markers of
      disease severity, as measured by the ALS Functional Rating Scale-revised (ALSFRS
      R) and rate of disease progression (DeltaFS), in addition to assessment of
      cortical motor function. RESULTS: Disease duration negatively correlated (R = 
      0.530, p < 0.01) with fasciculation intensity, while the DeltaFS positively
      correlated with the fasciculation number (R = 0.626, p < 0.01). In terms of
      potential central contributions to ectopic impulse generation, patients were
      classified into cohorts based on their fasciculation intensity and short interval
      intracortical inhibition (SICI). DeltaFS was significantly higher in patients
      with established hyperexcitability (low SICI) with high fasciculation intensity
      compared to those patients with minimal SICI change. CONCLUSIONS: Fasciculation
      intensity appears linked to disease progression and separately to markers of
      cortical dysfunction, specifically the advent of cortical hyperexcitability.
      SIGNIFICANCE: Assessment of the intensity of patient fasciculations is a
      noninvasive approach that may provide further insight disease pathophysiology in
      ALS.

PMID- 30114662
TI  - Strength and stability of EEG functional connectivity predict treatment response
      in infants with epileptic spasms.
AB  - OBJECTIVE: Epileptic spasms (ES) are associated with pathological neuronal
      networks, which may underlie characteristic EEG patterns such as hypsarrhythmia.
      Here we evaluate EEG functional connectivity as a quantitative marker of
      treatment response, in comparison to classic visual EEG features. METHODS: We
      retrospectively identified 21 ES patients and 21 healthy controls. EEG data
      recorded before treatment and after >=10 days of treatment underwent blinded
      visual assessment, and functional connectivity was measured using cross
      correlation techniques. Short-term treatment response and long-term outcome data
      were collected. RESULTS: Subjects with ES had stronger, more stable functional
      networks than controls. After treatment initiation, all responders (defined by
      cessation of spasms) exhibited decreases in functional connectivity strength,
      while an increase in connectivity strength occurred only in non-responders. There
      were six subjects with unusually strong pre-treatment functional connectivity,
      and all were responders. Visually assessed EEG features were not predictive of
      treatment response. CONCLUSIONS: Changes in network connectivity and stability
      correlate to treatment response for ES, and high pre-treatment connectivity may
      predict favorable short-term treatment response. Quantitative measures outperform
      visual analysis of the EEG. SIGNIFICANCE: Functional networks may have value as
      objective markers of treatment response in ES, with potential to facilitate rapid
      identification of personalized, effective treatments.

PMID- 30114664
TI  - Giant viruses and their mobile genetic elements: the molecular symbiosis
      hypothesis.
AB  - Among the virus world, Giant viruses (GVs) compose one of the most successful
      eukaryovirus families. By contrast with other eukaryoviruses, GV genomes contain
      a wide array of mobile genetic elements (MGEs) that encompass diverse, mostly
      prokaryotic-like, transposable element families, introns, inteins, restriction
      modification systems and enigmatic classes of mobile elements having little
      similarities with known families. Interestingly, several of these MGEs may be
      beneficial to the GVs, fulfilling two kinds of functions: (1) degrading host or
      competing virus/virophage DNA and (2) promoting viral genome integration,
      dissemination and excision into the host genomes. By providing fitness advantages
      to the virus in which they reside, these MGEs compose a kind of molecular
      symbiotic association in which both partners benefit from the presence of each
      other's. Thus, protective effects provided by some of these MGEs may have
      generated an arm race between competing GVs in order to encode the most diverse
      arsenal of anti-viral weapons, explaining the unusual abundance of MGEs in GV
      genomes by a kind of ratchet effect.

PMID- 30114665
TI  - Prevalence and incidence of postpartum depression among healthy mothers: A
      systematic review and meta-analysis.
AB  - This review aims to examine the prevalence and incidence of postpartum depression
      among healthy mothers without prior history of depression including postpartum
      depression and who gave birth to healthy full-term infants. A systematic search
      of ClinicalTrials.gov, CINAHL, EMBASE, PsycINFO, and PubMed was performed for
      English articles from the inception of the database to November 2017, as well as
      a manual search of the reference lists of the included articles, and an expert
      panel was consulted. Across 15,895 articles, 58 articles (N = 37,294 women) were
      included in the review. The incidence of postpartum depression was 12% [95% CI
      0.04-0.20] while the overall prevalence of depression was 17% [95% CI 0.15-0.20]
      among healthy mothers without a prior history of depression. Prevalence was
      similar regardless of the type of diagnostic tool used; however, there were
      statistical differences in the prevalence between different geographical regions,
      with the Middle-East having the highest prevalence (26%, 95% CI 0.13-0.39) and
      Europe having the lowest (8%, 95% CI 0.05-0.11). There was no statistical
      difference in prevalence between different screening time points, but an
      increasing prevalence was observed beyond six months postpartum. Intervention
      studies often neglect healthy mothers. This review reports a similar prevalence
      rate of postpartum depression among mothers without history of depression when
      compared to mothers with history of depression. Thus, future studies should place
      equal emphasis on this neglected group of mothers so that targeted interventions
      and follow-ups can be introduced at appropriate time points.

PMID- 30114666
TI  - Isolation, identification and characterization of lignocellulolytic aerobic and
      anaerobic fungi in one- and two-phase biogas plants.
AB  - Aerobic and anaerobic fungi are among the most effective plant biomass degraders
      known and have high potential to increase the efficiency of lignocellulosic
      biomass utilization, such as for biogas generation. However, limited information
      is available on their contribution to such industrial processes. Therefore, the
      presence of fungi along the biogas production chain of one-phase and two-phase
      biogas plants in Germany was analyzed. Seventeen aerobic species of Zygomycota,
      Ascomycota and Basidiomycota were identified, including efficient producers of
      lignocellulases, such as Trichoderma capillare isolated from a hydrolysis tank
      and Coprinopsis cinerea from fibers separated from pressed digestate. Five
      anaerobic fungal species of the phylum Neocallimastigomycota (comprising two
      novel clades) were present in an slightly acidic fermenter of a biogas plant fed
      with cow manure displaying endoglucanase transcriptional activity. The broad
      fungal presence demonstrated in this study can serve developing bioaugmentation
      systems with relevant lignocellulolytic fungi to improve biogas production from
      recalcitrant fiber material.

PMID- 30114667
TI  - Disentangling effects of temperature on microbial community and copper extraction
      in column bioleaching of low grade copper sulfide.
AB  - The lack of knowledge about responses of microbial community to temperature in
      copper sulfide bioleaching, and subsequent effects on copper extraction hampered
      understanding of how to improve bioleaching efficiency. This study presents first
      detailed quantitative data on microbial diversity and dynamics during bioleaching
      of low grade copper sulfide at different temperatures. The results demonstrate
      that temperature had significant effects on microbial community and copper
      extraction. The microbial structures on the ore surfaces were independent of
      communities in the leachates. Different species dominated the communities at
      different temperatures and portions of laboratory scale heap column. Moderate
      thermophiles rather than extreme thermophiles dominated the communities at 65 
      degrees C. The height of ore bed was sufficient to affect microbial communities
      at 30  degrees C and 65  degrees C. Sulfur-oxidizers were very important to
      improve copper extraction. High microbial diversity also were beneficial to
      enhance copper extraction within a certain temperature range in the final stage.

PMID- 30114668
TI  - Catalytic conversion of duckweed to methyl levulinate in the presence of acidic
      ionic liquids.
AB  - In this study, an efficient strategy is proposed for selective methyl levulinate
      production from duckweed, a typical fast-growing aquatic microalgae in warm and
      humid regions, in the presence of acidic ionic liquids (ILs). The results show
      that IL structure has a significant effect on its acidic strength, which finally
      determines the process efficiency for levulinate methyl generation. With the
      optimized catalyst of [C3H6SO3HPy]HSO4, 88.0% duckweed is consumed, resulting in
      a comparable methyl levulinate yield of 73.7% and a process efficiency of 81.8%
      at 170  degrees C for 5 h. Furthermore, this process is substantially influenced
      by the reaction condition, particularly, it is significantly temperature
      dependent. In addition, solvent has a remarkable intensified effect on the
      process efficiency, which dramatically decreases from 81.8 to 53.7% when methanol
      is replaced by water.

PMID- 30114669
TI  - Enhancement of the adaptability of anammox granules to zinc shock by appropriate
      organic carbon treatment.
AB  - Heavy metals, which are commonly present in high ammonia-containing wastewater,
      can cause inhibitory effects to anammox reaction. This study proposes a novel
      approach to enhance the adaptability of anammox granules to heavy metal [Zn(II)]
      shock by organic carbon (sodium acetate, NaAc) treatment, paying special
      attention to optimization of the treatment dosage and duration. For granules
      treated with 200 mg chemical oxygen demand (COD)/L NaAc for 2 d, the activity
      recovery (six cycles) efficiency after Zn(II) (40 mg/L) shock reached 127.4%. The
      extracellular polymeric substance (EPS) production increased by 168% and
      heterotrophic bacteria mildly proliferated (increased by 14%) in such granules
      compared with the control. The dramatic recovery capacity was likely due to the
      entrapment and barrier function of EPS and the outer-layer proliferated
      heterotrophic bacteria. This finding offers a useful process to enable maximum
      adaptability of anammox granules from heavy metals shocks, allowing anammox
      technology to be more widely applied.

PMID- 30114670
TI  - Maximizing the production of aromatic hydrocarbons from lignin conversion by
      coupling methane activation.
AB  - Maximizing the production of aromatic hydrocarbons from lignin conversion by
      coupling methane activation without solvent was investigated over Zn-Ga modified
      zeolite catalyst. The co-loading of Zn and Ga greatly improves lignin conversion,
      arene yield along with BTEX (i.e., benzene, toluene, ethylbenzene, and xylene)
      selectivity, which gives 37.4 wt% yield of aromatic hydrocarbons with 62.2 wt%
      selectivity towards BTEX at 400  degrees C and 3.0 MPa. Methane presence has a
      negligible impact on lignin conversion, but improves arene yield and BTEX
      selectivity. Liquid 13C, 1H and 2H NMR investigations confirm the incorporation
      of methane into the final arene products. The NMR results reveal that methane
      might be incorporated into both the methyl group and aromatic ring, possibly via
      methylation of aryl moieties and co-aromatization of alkyl moieties. Pyridine and
      ammonia as probes for surface acidity analysis of the developed catalysts
      demonstrate that HZSM5 modification with Zn and Ga species could redistribute BAS
      (Bronsted acid sites) and LAS (Lewis acid sites) and significantly increase the
      fraction of weak acidic sites on the catalyst, rendering better catalytic
      performance on the depolymerization of lignin to arene products with higher BTEX
      selectivity. The results reported in this work may open a novel route to a
      promising technique for lignin valorization into aromatics and cost-efficient
      utilizations of biomass and natural gas resources.

PMID- 30114672
TI  - Effects of age and individual experiences on tactile perception over the life
      span in women.
AB  - Tactile perception results from the interplay of peripheral and central
      mechanisms for detection and sensation of objects and the discrimination and
      evaluation of their size, shapes, and surface characteristics. For different
      tasks, we investigated this interaction between more bottom-up stimulus-driven
      and rather top-down attention-related and cognitive processes in tactile
      perception. Moreover, we were interested in effects of age and tactile
      experiences on this interaction. 299 right-handed women participated in our study
      and were divided into five age groups: 18-25 years (N = 77), 30-45 years (N =
      76), 50-65 years (N = 62), 66-75 years (N = 63) and older than 75 years (N = 21).
      They filled a questionnaire on tactile experiences and rated their skin as either
      very dry, dry, normal, or oily. Further they performed three tactile tests with
      the left and right index fingers. Sensitivity for touch stimuli was assessed with
      von Frey filaments. A sand paper test was used to examine texture discrimination
      performance. Spatial discrimination was investigated with a tactile Landolt ring
      test. Multivariate ANOVA confirmed a linear decline in tactile perceptual skills
      with age (F(3, 279) = 76.740; p < .000; pEta2 = 0.452), starting in early
      adulthood. Largest age effects were found for the Landolt ring test and smallest
      age effects for the Sand paper test, indicating different aging slopes. Tactile
      experiences had a positive effect on tactile performance (F (3,279) = 4.450; p =
      .005; pEta2 = 0.046) and univariate ANOVA confirmed this effect for the sand
      paper and the Landolt ring test, but not for the von Frey test. Using structural
      equation modelling, we confirmed two dimensions of tactile performance; one
      related to more peripheral or early sensory cortical (bottom-up) processes (i.e.,
      sensitivity) and one more associated with cognitive or evaluative (top-down)
      processes (i.e., perception). Interestingly, the top-down processes were stronger
      influenced by age than bottom-up ones, suggesting that age-related deficits in
      tactile performance are mainly caused by a decline of central perceptive
      evaluative capacities rather than by reduced sensitivity.

PMID- 30114671
TI  - Molecular characterization of long-term impacts of macrophytes harvest management
      in constructed wetlands.
AB  - There is little understanding of constructed wetlands (CWs) microbial community
      patterns in response to harvest management. Therefore, long-term impacts of
      harvesting Phragmites australis (Cav.) Trin. ex Steudel annually in November on
      the activity and community structure of microorganisms critical to the treatment
      efficiency of CW are elucidated. Findings show exponential increases in P.
      australis density and biomass with continuous harvesting, up to three times over
      unharvested CW. High-throughput pyrosequencing analysis demonstrates that plants
      harvesting improves the microbial community diversity and richness significantly,
      and more particularly, the relative abundance of Flavobacterium,
      Paenisporosarcina, and Povalibacter, which are extensively associated with CW
      performance. Consequently, increased plants biomass resulted in enhanced plants
      nutrients uptake in harvested (56.5 g N/m2, 5.5 g P/m2) than unharvested CWs
      (17.5 g N/m2, 1.8 g P/m2), whereas improved rhizosphere microclimates
      significantly enhanced nutrients removals in harvested CW (TN 109.9 g/m2 vs 67.4
      g/m2, TP 18.0 g/m2 vs 13.0 g/m2).

PMID- 30114673
TI  - Targets for repair: detecting and quantifying DNA damage with fluorescence-based
      methodologies.
AB  - Detection and characterization of DNA damage is essential for evaluating
      genotoxicity, monitoring DNA repair, developing biomarkers for exposures, and
      evaluating the efficacy of chemotherapies. These diverse applications for DNA
      damage measurements have spurred the continual development and refinement of
      methodologies for detecting, characterizing, and quantifying DNA damage from
      isolated DNA and in cells and tissues. Current damage detection methods cover a
      wide range of techniques from radiolabeling to mass spectrometry, and use of
      these techniques varies widely based on expense, expertise, and knowledge of
      adduct formation. More generalizable, easy-to-use methods for detecting and
      quantifying DNA damage are needed, and there has been an emergence of
      fluorescence-based methodologies to address this need. Developments in these
      fluorescence-based strategies are reviewed here.

PMID- 30114674
TI  - Positive heavy drinking attitude mediates the association between college alcohol
      beliefs and alcohol-related outcomes.
AB  - College alcohol beliefs and personal attitudes about alcohol use are important
      predictors of alcohol use and related problems both cross-sectionally and over
      time. However, little work has examined these constructs together and how they
      may influence one another in predicting various alcohol related outcomes over
      time. The current study aimed to evaluate one's attitude toward heavy drinking as
      a mediator of the association between college alcohol beliefs and drinking
      related outcomes over a 12-month period of time. Participants were mandated
      students (n = 568; 28% female) who violated campus alcohol policy and received a
      Brief Motivational Intervention. Analyses included the use of linear regression
      for prospective predictions as well as PROCESS to evaluate the proposed mediation
      models. Overall, the results indicate that one's attitude toward heavy drinking
      significantly mediates the association between college alcohol beliefs and drinks
      per week, binge frequency, as well as alcohol-related problems over 12 months.
      These findings provide a compelling rationale for incorporating both college
      alcohol beliefs and attitudes in the development and refinement of intervention
      strategies.

PMID- 30114675
TI  - Impact of poorly controlled epilepsy in the Republic of Guinea.
AB  - PURPOSE: To characterize people with epilepsy (PWE) presenting to a free
      neurology consultation and antiepileptic drug (AED) service in the Republic of
      Guinea. METHODS: Guinea is a low-income country in West Africa that recently
      experienced an Ebola Virus Disease epidemic. Community-dwelling PWE were seen at
      a public referral hospital in Conakry, the capital city. During two visits in
      2017, an African-U.S. team performed structured interviews and
      electroencephalograms and provided AEDs. RESULTS: Of 257 participants (143
      children, 122 female), 25% had untreated epilepsy and 72% met our criteria for
      poorly controlled epilepsy. 59% had >100 lifetime seizures, and 58% reported a
      history consistent with status epilepticus. 38 school-aged children were not in
      school and 26 adults were unemployed. 115 were not currently taking an AED,
      including 50 participants who had previously taken an AED and stopped. Commonly
      cited reasons for AED discontinuation were perceived side effects,
      unaffordability, and unavailability of AEDs. Traditional medicine use was more
      frequent among children versus adults (92/143 vs. 60/114, p = 0.048). 57
      participants had head injuries, 29 had burns, and 18 had fractures. In a
      multivariable regression analysis, >100 lifetime seizure count was strongly
      associated with seizure-related injury (p < 0.001). Burns were more likely to
      occur among females (p = 0.02). CONCLUSIONS: There is an urgent need to improve
      the standard of care for PWE in Guinea. Several missed opportunities were
      identified, including low use of AEDs and high use of traditional medicines,
      particularly in children. Targeted programs should be developed to prevent
      unintentional injury and improve seizure control.

PMID- 30114676
TI  - Enhanced photorespiration in transgenic rice over-expressing maize C4
      phosphoenolpyruvate carboxylase gene contributes to alleviating low nitrogen
      stress.
AB  - The objective of this study was to reveal the physiological and molecular
      mechanisms of low-nitrogen (N) tolerance in transgenic plant lines containing C4
      phosphoenolpyruvate carboxylase (C4-PEPC) gene. The transgenic rice lines only
      over-expressing the maize C4-PEPC) (PC) and their untransformed wild type,
      Kitaake (WT), were used in this study. At different N levels, the dry weight,
      total N content, carbon and N levels, photorespiration-related enzymatic
      activities, gene expression levels and photorespiration-related product
      accumulations were measured, as were the transgenic lines' agronomic traits. The
      PC line, having lower total N and higher soluble sugar contents, was more
      tolerant to low-N stress than WT, which was consistent with its higher PEPC and
      lower N-assimilation-related enzyme activity levels. The photosynthetic
      parameters, enzymatic activity levels, transcripts and products related to
      photorespiration in PC were also greater than in WT under low-N conditions. This
      study showed that increased carbon levels in transgenic rice lines overexpressing
      C4-PEPC could help regulate the photorespiratory pathway under low-N conditions,
      conferring low-N tolerance and a higher grain yield per plant.

PMID- 30114677
TI  - Characterization of human parainfluenza virus-3 circulating in Israel, 2012-2015.
AB  - BACKGROUND: Human parainfluenza virus 3 (hPIV-3) causes respiratory tract
      infection. OBJECTIVES: The objective of this study was to describe the
      epidemiology of hPIV-3 infection among hospitalized patients and characterize the
      circulating strains. STUDY DESIGN: A cross-sectional study was conducted using
      respiratory samples of 15,946 hospitalized patients with respiratory symptoms in
      2012-2015 in Israel. All samples were subjected to q-PCR and q-RT-PCR to
      determine the presence of hPIV-3 and other respiratory viruses. Samples positive
      for hPIV-3 were subjected to molecular typing and phylogenetic analysis. RESULTS:
      Overall, 547 samples 3.4% (95% CI 3.2-3.7) were positive for hPIV-3. Of these 87
      (15.9%) were mixed infections; 41.4% with adenovirus, 40.2% with RSV (40.2%) and
      19.5% influenza A viruses. The prevalence of hPIV-3 was highest (5.1%) in
      children aged 0-4 years. Hospitalization in oncology department was associated
      with increased likelihood of hPIV-3 infection: adjusted odds ratio [aOR] 2.29
      (95% confidence intervals [CI] 1.78-2.96), as well as hospitalization in organ
      transplantation department: aOR 3.65 (95% CI 2.80-4.76). The predominant lineages
      were C3c (62.3%) and C1b (24.6%), followed by sub-lineages C5 (8.7%) and C3b
      (2.9%). A new sub-lineage emerged in our analysis, named C1d, which was 17 (1.5%)
      nucleotide different from C1a, 25 (2.2%) nucleotide different from C1b and 24
      (2.1%) nucleotide different from C1c. DISCUSSION: Young children and
      immunocompromised patients are likely the risk groups for severe respiratory
      infections with hPIV-3. Strains belonging to lineages C3c and C1b, which are
      present worldwide, should be targeted in vaccine development. The emergence of
      new lineage might have public health implications and on vaccine development.

PMID- 30114678
TI  - WU polyomavirus detected in children with severe respiratory failure.
AB  - BACKGROUND: WU polyomavirus (WUPyV) is a relatively new virus associated with
      respiratory infections. However, its role is unclear in children with severe
      respiratory failure. OBJECTIVES: We aimed to evaluate the characteristics of
      severe respiratory failure associated with WUPyV infection in children. STUDY
      DESIGN: We retrospectively reviewed cases of respiratory tract infection at a
      tertiary children's hospital in Japan and performed real-time polymerase chain
      reaction (PCR) for WUPyV using residual extracted nucleic acid samples taken from
      respiratory tract samples of pediatric patients primarily with respiratory
      failure. We investigated the clinical characteristics of patients positive for
      WUPyV and assessed samples positive for WUPyV for other respiratory pathogens
      using multiplex PCR. RESULTS: WUPyV was detected in 14 of 318 specimens of
      respiratory tract infections. The median age was 34 months and males were
      predominant (n = 11, 64%). An underlying disease was found in 11 (79%) patients
      including five preterm and three immunocompromised patients. The most common
      clinical diagnosis was pneumonia (n = 13, 93%). The majority of the samples were
      endotracheal tube aspirates (n = 11, 79%). Other viruses were co-detected in nine
      (64%) patients, while WUPyV was the only pathogen detected in five patients with
      a history of admission to the neonatal intensive care unit. These five patients
      presented with fever and cough, and perihilar infiltrates were detected on chest
      radiograph in several days. CONCLUSIONS: WUPyV was detected in children with
      severe respiratory failure independently or concurrently with other pathogens.
      WUPyV can be a pathogen for children with a history of preterm birth or an
      underlying disease.

PMID- 30114679
TI  - The added value of magnifying endoscopy in diagnosing patients with certain
      gastroesophageal reflux disease.
AB  - PURPOSE: In most cases gastroesophageal reflux disease proceeds without
      macroscopic erosions in the esophagus. We aimed to clarify if abnormalities
      detectable in magnifying endoscopy may offer additional diagnostic criteria for
      gastroesophageal reflux disease and to what histopathologic structures do they
      correspond. PATIENTS/METHODS: Esophageal mucosa above and below Z-line was
      evaluated under x115 magnification in 67 gastroesophageal reflux disease patients
      (11 with erosive reflux disease, 28 with Barrett's esophagus, 28 with nonerosive
      reflux disease) and in 12 patients without gastroesophageal reflux disease
      (negative control group). Features characteristic of gastroesophageal reflux
      disease were specified by comparing erosive reflux disease and Barrett's
      esophagus patients with negative control group. Afterwards the presence of
      identified features were evaluated in nonerosive reflux disease group.
      Interobserver agreement in the recognition of the proposed criteria was rated.
      Biopsies collected from the mucosa above Z-line were evaluated histologically
      after hematoxylin and eosin staining. RESULTS: Endoscopic lesions characteristic
      of gastroesophageal reflux disease were: microerosions, abnormal intrapapillary
      capillary loops, obscured palisade vessels, white points, big triangular
      indentations of Z-line and villous mucosa below Z-line. The presence of two or
      more of the above features indicated gastroesophageal reflux disease with 97%
      sensitivity and 75% specificity. Substantial interobserver agreement was achieved
      in evaluation of obscured palisade vessels, abnormal intrapapillary capillary
      loops and white points. Endoscopic lesions were correlated to histology. Lesions
      identified with magnifying endoscopy were helpful in discerning between negative
      control group and nonerosive reflux disease patients. CONCLUSIONS: Magnifying
      endoscopy reveals abnormalities that can be used as additional endoscopic
      diagnostic criteria of gastroesophageal reflux disease.

PMID- 30114681
TI  - Factor X Deficiency Caused by Nonsecretory Myeloma Successfully Corrected with
      Bortezomib: A Case Report and Review of the Literature.
AB  - A 62-year-old female presenting with anemia and extensive hemorrhages is
      reported. Coagulation tests showed significantly prolonged prothrombin time (PT)
      and activated partial thromboplastin time. Decreased levels of clotting factor X
      activity were determined (5.4%). Bone marrow biopsy revealed neoplastic plasma
      cells. Serum and urine protein electrophoresis were both negative for monoclonal
      gammopathy, and both bone marrow and abdominal fat biopsies were negative for
      amyloid deposition. The patient was diagnosed as suffering from nonsecretory
      multiple myeloma (MM) complicated by acquired factor X deficiency. A complete
      response (CR) of the myeloma and recovery of factor X activity (56.6%) were
      achieved after the administration of treatment, including chemotherapy and
      bortezomib. We suggest that patients with nonsecretory MM might present with
      factor X deficiency and should be carefully screened for light chain amyloidosis.
      Novel agents such as bortezomib should be highly considered as treatment in these
      patients.

PMID- 30114680
TI  - Effects of a violence prevention intervention in schools and surrounding
      communities: Secondary analysis of a cluster randomised-controlled trial in
      Uganda.
AB  - The Good School Toolkit is effective in reducing staff violence against children
      in Ugandan primary schools. A secondary analysis of cluster-randomised trial data
      was conducted to investigate intervention effects on school operational culture,
      and on normative beliefs and violence against children from caregivers outside of
      school. Students and staff completed cross-sectional surveys at baseline in 2012
      and follow-up in 2014. Students' caregivers completed follow-up surveys only.
      Data from 3820 students, 597 staff, and 799 caregivers were included in cross
      sectional analyses at follow-up. Statistically significant intervention effects
      were observed for aspects of school operational culture, including students'
      greater perceived emotional support from teachers and peers, students' greater
      identification with their school, students' and staffs' lower acceptance of
      physical discipline practices in school, and students' and staffs' greater
      perceived involvement in school operations. Outside the school, the intervention
      was associated with significantly lower normative beliefs accepting the use of
      physical discipline practices in schools (adjusted mean difference, AMD: -0.77;
      95%CI: -0.89 to -0.66; p < 0.001) and at home (AMD: -0.67; 95%CI: -0.80 to -0.54;
      p < 0.001), based on aggregated caregiver reports. No differences between groups
      were observed in past-week violence against children at home. This intervention
      shows promise as a platform for addressing violence against children within the
      school environment and surrounding community.

PMID- 30114682
TI  - The Impact of Depressive Disorder Symptoms and Subtypes on 6-Year Incidence of
      Somatic Diseases.

PMID- 30114683
TI  - Implementation of a Systematic Literature Search Strategy in a National Breast
      Cancer Guideline: The Relevance of Systemic Therapy in Lymph Node Recurrent
      Disease.
AB  - PURPOSE: Our aim was to implement a structured literature search using PICO
      (patient/intervention/comparison/outcome) questions and a standardized consensus
      method for the German Guideline 'Detection, diagnostics, therapy and follow-up of
      Breast Cancer' using, as an example, the significance of systemic therapy in
      lymph node recurrent disease (LNRD). METHODS: We defined specified PICO questions
      according to the clinical significance of a recommendation for systemic therapies
      in locoregional LNRD. A methodologist performed a systematic literature search
      including randomized controlled trials, systematic reviews and observational
      studies (2007-2016). In a consensus conference, the level of evidence and
      consensus was determined and the clinical recommendation was adopted. RESULTS: In
      total 143 publications were identified according to the search strategy including
      14 duplicates, which were excluded. 4 publications were included based on
      experts' choice. The team excluded 119 publications, leaving 14 that were then
      screened by a full text search. Finally, 1 publication was found to be of
      methodologically and clinically reliable content. The conclusion of this
      publication in favor of systemic therapy for LNRD received strong consent from
      the consensus conference. CONCLUSIONS: The literature search strategy using PICO
      questions helped to achieve a fast and standardized selection of publications.
      The recommendation concerning systemic treatment of LNRD was first implemented in
      the update of the German Breast Cancer guideline.

PMID- 30114684
TI  - The Use of a Long-Acting Somatostatin Analogue (Lanreotide) in Three Children
      with Focal Forms of Congenital Hyperinsulinaemic Hypoglycaemia.
AB  - BACKGROUND: A long-acting somatostatin analogue (lanreotide) is used in the
      management of a diazoxide-unresponsive diffuse form of congenital hyperinsulinism
      (CHI). However, no reports of its use in patients with the focal form of CHI
      exist. Case 1: A 1-month-old boy diagnosed with diazoxide-unresponsive CHI due to
      a paternal heterozygous ABCC8 gene mutation showed partial response to
      octreotide. 18F-DOPA-PET/CT scan revealed a focal lesion in the pancreatic head.
      Surgical removal of the lesion was unsuccessful. He was switched to monthly
      lanreotide treatment at the age of 11 months, which stabilised his blood glucose
      over a 12-month period. Case 2: A 1-month-old boy with diazoxide-unresponsive CHI
      due to a paternal heterozygous KCNJ11 gene mutation was partially responsive to
      octreotide. 18F-DOPA-PET/CT scan confirmed a focal pancreatic head lesion. Over 6
      months, he underwent 3 lesionectomies and afterwards responded to octreotide. At
      the age of 9 months, treatment was switched to monthly lanreotide. Currently, he
      is aged 3, with stable glycaemia, and improved fasting tolerance. Case 3: A 3
      week-old girl with a paternal heterozygous ABCC8 gene mutation was unresponsive
      to diazoxide. 18F-DOPA-PET/CT scan confirmed a focal pancreatic head lesion. She
      responded to octreotide, and her parents preferred to avoid pancreatic surgery.
      At the age of 20 months, treatment was switched to monthly lanreotide, resulting
      in euglycaemia over the last 7 months. CONCLUSION: CHI patients with focal
      pancreatic head lesions are challenging, especially if not surgically amenable.
      Conservative treatment is preferable, and lanreotide might be an option. The
      therapeutic impact of lanreotide treatment in patients with the focal forms of
      CHI should be confirmed in prospective studies with close monitoring of the side
      effects.

PMID- 30114686
TI  - Komodo Dragon Predation on Crab-Eating Macaques at the Rinca Island's Visitor
      Centre, Indonesia.
AB  - We investigated the proportion of crab-eating macaques in the diet of Komodo
      dragons and quantified the spatial habitat use between the species as a proxy for
      predation threat and in relation to prey availability due to ecotourism. In 2013,
      in Loh Buaya valley of Rinca Island, Komodo National Park, we conducted
      macroscopic identification of hairs, claws, dentition and osteological remains of
      consumed prey. For habitat use, we quantified the use of vertical strata by
      macaques through focal animal sampling. For Komodo dragons in the valley,
      macaques were a significant component of their diet (20.7%), ranking second after
      rusa deer (58.6%); the proportion of macaques we observed in the diet is much
      higher than in previous studies. An increased use of the forest floor by macaques
      at this site may increase their vulnerability as a prey species, especially in
      the daytime when tourist presence impacts the availability of other favoured prey
      species.

PMID- 30114685
TI  - Association of Antioxidative Enzymes Polymorphisms with Efficacy of Platin and
      Fluorouracil-Based Adjuvant Therapy in Gastric Cancer.
AB  - BACKGROUND/AIMS: Imbalance of oxidative/antioxidative enzymes in cells is
      associated with carcinogenesis and cancer cell chemoresistance. The aim of this
      study was to examine the clinical significance of potentially functional single
      nucleotides polymorphisms (SNPs) in antioxidative enzymes, GPxs and CAT, in
      stages II and III gastric cancer patients. METHODS: A total of 591 gastric cancer
      patients who had radical gastrectomy were recruited. 207 patients received
      platinum and fluorouracil-based (PF-based) adjuvant chemotherapy and 384 patients
      were untreated. GPx1 rs1050450, GPx2 rs4902346, GPx3 rs736775, rs3828599 and CAT
      rs769218 were genotyped in the DNA samples extracted from paraffin-embedded tumor
      tissue. RESULTS: CAT rs769218 was significantly correlated with the overall
      survival (OS) in the dominant model (P = 0.014). Multivariate analysis revealed
      that CAT rs769218 GA/AA (HR, 0.715; 95%CI, 0.562-0.910, P = 0.006) was an
      independent prognostic marker indicating improved survival. After adjustments,
      GPx3 rs736775 TC/CC was significantly associated with improved OS (HR, 0.621;
      95%CI, 0.399-0.965; P=0.034) in patients treated with PF-based adjuvant
      chemotherapy, and CAT rs769218 GA/AA was significantly associated with improved
      OS (HR, 0.646; 95% CI, 0.482-0.864; P = 0.003) in the untreated patients. PF
      based chemotherapy significantly decreased risk of death for patients carrying
      GPx3 rs736775 TC/CC and age <= 60 years or with diffused type adenocarcinoma
      compared to surgery alone. CONCLUSION: our findings suggested CAT rs769218 and
      GPx3 rs736775 may be considered as prognostic markers in gastric cancer. Patient
      stratification by GPx3 rs736775 and conventional pathological parameters may
      provide additional predictive information in treatment decision-making.

PMID- 30114687
TI  - Agranulocytosis Associated with Waldenstrom Macroglobulinemia.
AB  - Currently, there are only 2 case reports of Waldenstrom macroglobulinemia (WM)
      associated with severe neutropenia. This is a case report of a woman with a past
      medical history of WM who presented with neutropenic fever. The patient's febrile
      neutropenia resolved after RCD chemotherapy (cyclophosphamide 750 mg/m2,
      dexamethasone 20 mg, and rituximab 375 mg/m2). Fourteen days after
      administration, the neutrophil level had started to rise and normalized after 6
      days. To the best of our knowledge, this is the 3rd reported case of
      agranulocytosis due to WM.

PMID- 30114688
TI  - Associated Pulmonary Hypertension Is an Independent Contributor to Exercise
      Intolerance in Chronic Fibrosing Interstitial Pneumonias.
AB  - BACKGROUND: Associated pulmonary hypertension (APH) is frequently observed in
      fibrosing interstitial pneumonias (FIP), such as idiopathic pulmonary fibrosis
      (IPF). APH is associated with worse prognosis, but it remains unclear whether it
      is associated with greater functional impairment. Six-minute walk distance (6MWD)
      is widely used to assess functional capacity in pulmonary hypertension and FIP.
      OBJECTIVES: To investigate if APH independently contributes to exercise
      intolerance in FIP, irrespective of the extent of underlying fibrosis. METHODS:
      Patients diagnosed with FIP (September 2009 to June 2017) were included in the
      study if they underwent right heart catheterization, high-resolution chest
      computed tomography (HRCT), and 6MWD within 3 months. Recruitment was not limited
      only to patients undergoing lung transplant assessment. APH was defined as mean
      pulmonary artery pressure (mPAP) >=25 mm Hg. The extent of fibrosis was
      quantified on HRCT using a visual fibrosis score by 2 separate observers.
      RESULTS: Seventy-two patients (60 with IPF) were identified. Fifty-five patients
      had APH. mPAP was not significantly different in subgroups stratified according
      to the extent of fibrosis on HRCT. Pulmonary vascular resistance (PVR) was the
      strongest predictor of 6MWD on both univariate and stepwise regression analyses,
      and remained so considering only patients with normal wedge pressure (< 15 mm Hg)
      (n = 61). HRCT fibrosis score and pulmonary function tests did not significantly
      correlate with 6MWD. CONCLUSIONS: In patients with FIP, PVR is a significant
      contributor of 6MWD, independently from the extent of fibrosis on HRCT. These
      results strengthen both the rationale to use 6MWD as endpoint in FIP and to
      target APH with specific therapies.

PMID- 30114689
TI  - Prognostic Implication of Urothelial Stem Cell Markers Differs According to
      Primary Tumour Location in Non-Muscle-Invasive Bladder Cancer.
AB  - BACKGROUND/AIMS: This study aimed to validate the value of urothelial stem cell
      (USC) markers DeltaNp63, integrin beta4, CD47, and CD44v6 in predicting the
      prognosis of non-muscle invasive bladder cancer (NMIBC) located in different
      anatomic regions of bladder. METHODS: The study reviewed the clinicopathologic
      data of 169 patients with NMIBC. Using real-time PCR and immunohistochemistry,
      the expression of DeltaNp63, integrin beta4, CD47, and CD44v6 in archived
      specimens of patients with NMIBC were validated. Kaplan-Meier analysis and Cox
      proportional hazards model were used to assess the prognostic impact of USC
      markers for recurrent-free survival (RFS). RESULTS: The Real-time PCR data showed
      that the expression of USC markers were higher in tumors located in the trigone
      and posterior wall than that in other regions of bladder (P< 0.05). Statistical
      analysis showed that high expression of DeltaNp63 was correlated with tumor stage
      (P=0.023) and tumor size (P=0.001), that high expression of integrin beta4 was
      correlated with tumor stage (P=0.026), tumor grade (P=0.005) and tumor size
      (P=0.003), and that high integrin beta4, CD47, and CD44v6 expression were
      significantly associated with tumor recurrence (P=0.032, P=0.010, and P=0.043,
      respectively). Moreover, high expression of DeltaNp63 and integrin beta4 was
      correlated with poor RFS in patients with tumors located in the trigone (P=0.025
      and P=0.023, respectively). High expression of integrin beta4, CD47, and CD44v6
      was correlated with poor RFS in patients with tumors in the posterior wall
      (P=0.017, P=0.033 and P=0.047, respectively). High expression of integrin beta4
      and CD47 was correlated with poor RFS in patients with tumors in the
      trigone/posterior wall area (P=0.002 and P=0.005, respectively). CONCLUSION: Our
      results suggest that USC markers are linked with poor prognosis of NMIBC
      patients, especially in patients with tumors in the trigone and posterior wall.

PMID- 30114690
TI  - Long Noncoding RNA BCYRN1 Promotes the Proliferation of Colorectal Cancer Cells
      via Up-Regulating NPR3 Expression.
AB  - BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) constitute a large proportion of
      noncoding transcripts that have recently emerged as a new class of important
      regulators in cancers. LncRNA BCYRN1, also known as BC200, has a potential
      function in tumorigenesis. However, the clinical significance of BCYRN1 and its
      effect on colorectal cancer (CRC) progression remains unclear. METHODS:
      Quantitative reverse transcriptase PCR (qRT-PCR) was performed to investigate the
      expression of BCYRN1 in CRC tissues and cell lines. The biological function of
      BCYRN1 was also investigated through knockdown and overexpression of BCYRN1 in
      vitro. Microarray bioinformatics analysis was performed to analyze the putative
      targets of BCYRN1. RESULTS: The results showed that BCYRN1 expression was
      significantly upregulated in 96 CRC tumor tissues compared with para-carcinoma
      control tissues. Additionally, BCYRN1 overexpression was associated with larger
      tumor size and advanced pathological stages in CRC patients. In vitro BCYRN1
      knockdown significantly inhibited the proliferation and apoptosis of CRC cells.
      Furthermore, NPR3 was identified to be a target of BCYRN1 and was downregulated
      by BCYRN1 knockdown. CONCLUSION: Together, we provide the first evidence that
      BCYRN1 plays an oncogenic role in CRC cells. BCYRN1 may be a promising prognostic
      biomarker and a potential therapeutic target for CRC.

PMID- 30114691
TI  - Evidence of Decreased Activity in Intermediate-Conductance Calcium-Activated
      Potassium Channels During Retinoic Acid-Induced Differentiation in Motor Neuron
      Like NSC-34 Cells.
AB  - BACKGROUND/AIMS: Intermediate-conductance Ca2+-activated K+ (IKCa; KCa3.1 or
      KCNN4) channels affect the behaviors of central neurons including motor neurons.
      The mechanism through which neuronal differentiation is related to the activity
      of these channels remains largely unclear. METHODS: By using various molecular
      biology tools and electrophysiological measurements, we investigated possible
      changes in the activity of IKCa channels in a retinoic acid (RA)-induced
      differentiation process in motor neuron-like NSC-34 cells. RESULTS: The protein
      and messenger RNA expression of KCa3.1 substantially diminished as NSC-34 cells
      were differentiated with low serum (1%) and 1 uM RA. In whole-cell current
      recordings, the density of delayed-rectifier K+ currents obtained from
      differentiated cells was elevated. However, the density of a ramp pulse-elicited
      K+ current that was sensitive to blockage by 1-((2-chlorophenyl)
      (diphenyl)methyl)-1H-pyrazole (TRAM-34)-an inhibitor of IKCa channels-was
      significantly higher in undifferentiated NSC-34 cells than in differentiated
      cells. In undifferentiated cells, the activity of IKCa channels was readily
      detected and the probability of channel openings was resistant to stimulation by
      diazoxide or suppression by verruculogen. Furthermore, this probability was
      increased by 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one or 9
      phenanthrol and reduced by TRAM-34. The channel-opening probability decreased in
      RA-induced differentiated cells, whereas the single-channel conductance of IKCa
      channels did not differ between undifferentiated and differentiated cells.
      Moreover, the slow component of the mean closed time in these channels was
      significantly shorter in undifferentiated cells than in differentiated cells;
      however, the mean open time in the channel remained unchanged as cells were
      differentiated. CONCLUSION: RA-induced differentiation in neurons could exert a
      suppressive effect on the activity of IKCa channels.

PMID- 30114692
TI  - Identifying Barriers to Idiopathic Pulmonary Fibrosis Treatment: A Survey of
      Patient and Physician Views.
AB  - BACKGROUND: Antifibrotics are recommended for the treatment of individuals with
      idiopathic pulmonary fibrosis (IPF), but treatment use remains at ~60%.
      OBJECTIVE: To investigate the views of individuals with IPF and pulmonologists on
      the diagnosis and management of IPF to understand treatment patterns. METHODS:
      Interviews and/or online surveys were completed by patients and pulmonologists
      from Canada, France, Germany, Italy, Spain, and the UK. Responses from physicians
      were analyzed by time between diagnosis and treatment initiation in the majority
      of patients with IPF (group A, > 4 months; group B, <=4 months). Statistical
      comparisons between physicians were undertaken using z tests, with p < 0.05
      considered statistically significant. RESULTS: The physicians in group A saw
      fewer patients, were less comfortable discussing the IPF prognosis with patients,
      and had less belief in the benefits of antifibrotic treatments than the
      physicians in group B. These physicians' attitudes contrasted with those of the
      patients, who wanted more information about the IPF prognosis and pharmacological
      treatment options at diagnosis and were more concerned about preventing disease
      progression than avoiding medication side effects. Differences between countries
      were found regarding physicians' comfort in discussing the prognosis at diagnosis
      and access to care. CONCLUSIONS: Several barriers to antifibrotic treatment,
      principally reflecting the differing views and values of patients and physicians,
      were identified in this study, suggesting a need for better patient-physician
      communication about pharmacological therapy for IPF.

PMID- 30114695
TI  - Why Is the Immunoglobulin Heavy Chain Gene Mutation Status a Prognostic Indicator
      in Chronic Lymphocytic Leukemia?
AB  - The immunoglobulin heavy chain gene (IgHV) mutation status correlates with the
      clinical outcome of patients with chronic lymphocytic leukemia (CLL) treated with
      chemoimmunotherapy. Why the survival rate of patients with unmutated IgHV is
      worse than that of patients with mutated IgHV is unknown. CLL cells with
      unmutated IgHV were thought to originate from naive B lymphocytes, whereas CLL
      cells with mutated IgHV were thought to arise from B cells that have undergone
      somatic hypermutation (SHM). Cell surface protein expression profile and gene
      expression studies showing that all CLL cells, regardless of their IgHV mutation
      status, are of postgerminal center origin, negated this hypothesis. We hereby
      propose that all CLL cells undergo SHM and their proliferation rate determines
      their IgHV mutation status. DNA breaks, accumulated during SHM, are restored by
      various DNA repair mechanisms. In rapidly dividing cells DNA breaks are repaired
      by the efficient high-fidelity homology-directed DNA repair apparatus, whereas in
      slowly dividing cells they are repaired by the inefficient low-fidelity
      nonhomology end-joining repair mechanism. Accordingly, a low IgHV mutation rate
      is found in rapidly dividing cells whereas a high mutation rate is typically
      found in slowly dividing cells. Thus, the proliferation rate of CLL cells
      determines the IgHV mutation status and patients' clinical outcome.

PMID- 30114694
TI  - Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem
      Cell Injection in Rat Liver Fibrosis Model.
AB  - BACKGROUND/AIMS: The most appropriate route for bone marrow-derived mesenchymal
      stem cell (BM-MSC) transplantation in the management of liver fibrosis remains
      controversial. This study investigated the therapeutic efficacy of intravenous
      and intrasplenic BM-MSC transplantation on carbon tetrachloride (CCl4)-induced
      rat liver fibrosis. METHODS: Fifty rats were divided into 5 groups (n = 10 rats
      per group): healthy control group, CCl4 group, CCl4/ recovery group, CCl4/BM-MSC
      intravenous group, and CCl4/BM-MSC intrasplenic group. BM-MSCs were isolated,
      labeled with green fluorescent protein (GFP), and injected into fibrotic rats
      either intravenously or intrasplenically. Gene expression of interleukins (IL
      1beta and IL-6), interferon (INF)-gamma, hepatic growth factor, and the
      hepatocyte-specific marker cytokeratin 18 was estimated by quantitative real-time
      reverse transcription-polymerase chain reaction. Vascular endothelial growth
      factor and connective tissue growth factor was detected by western blot analysis
      and enzyme-linked immunosorbent assay, respectively. At 2 weeks after intravenous
      and intrasplenic BM-MSC injections, GFP-positive cells were detected in liver
      tissue. RESULTS: Both routes achieved a similar enhancement of liver function,
      which was confirmed by histopathological examination. The intravenous route was
      more effective than the intrasplenic route in reducing gene expression levels of
      IL-1beta, IL-6, and INF-gamma. However, fibrotic changes were still observed in
      the recovery group. CONCLUSION: Intravenous BM-MSC injection was an efficient and
      appropriate route for BM-MSC transplantation for the management of liver
      fibrosis.

PMID- 30114693
TI  - Overexpressed D2 Dopamine Receptor Inhibits Non-Small Cell Lung Cancer
      Progression through Inhibiting NF-kappaB Signaling Pathway.
AB  - BACKGROUND/AIMS: Non-small cell lung cancer (NSCLC) is one of the deadliest
      cancers worldwide. Dopamine receptor D2 (DRD2) has multiple roles in clinical
      progression of NSCLC and functional maintenance of cancer cells. However, little
      is known about the molecular mechanism. Here, we clarified whether DRD2 inhibits
      lung cancer progression and identified the underlying downstream signaling.
      METHODS: DRD2 mRNA and protein levels were detected in clinical specimens by qRT
      PCR and immunohistochemistry, respectively. MTT and colony formation assays were
      applied to analyze cell proliferation. The underlying molecular mechanism was
      identified by dual luciferase, western blot, qRT-PCR, cAMP detection,
      immunoprecipitation, and chromatin immunoprecipitation assays. A murine NSCLC
      model was used to clarify the role of DRD2 in tumor cell proliferation. RESULTS:
      We found that DRD2 ablated tumor cell growth. DRD2 expression in NSCLC tissues
      was lower than in adjacent normal lung tissues. Moreover, DRD2 mRNA and protein
      levels in NSCLC were negatively correlated with the tumor size, TNM status, and
      patient overall survival. In vitro experiments showed that disruption of DRD2
      promoted the proliferation of NSCLC cell lines A549 and SK-MES-1 by inhibiting
      the NF-kappaB signaling pathway. Furthermore, DRD2 overexpression not only
      blocked lipopolysaccharide-induced A549 and SK-MES-1 cell proliferation and
      growth, but also inhibited the tumorigenesis in murine xenograft models.
      CONCLUSION: These results indicate that DRD2 may be a potential therapeutic
      target for lung cancer patients with high DRD2 expression by ablating the NF
      kappaB signaling pathway.

PMID- 30114696
TI  - Medicine and Economy in an Ever-Changing World.

PMID- 30114697
TI  - ANTXR1 Intronic Variants Are Associated with Fetal Hemoglobin in the Arab-Indian
      Haplotype of Sickle Cell Disease.
AB  - Disease severity of sickle cell anemia is highly variable, and it is commonly
      accepted that fetal hemoglobin (HbF) levels play a major role as an ameliorating
      factor. Investigation of genetic variants have identified several genes to be the
      principal influencers of HbF regulation. Here, we further elucidated the
      association of rs4527238 and rs35685045 of ANTXR1 genes in the context of HbF
      level variance in sickle cell anemia patients of the Arab-Indian haplotype.
      Samples from 630 sickle cell anemia patients were analyzed for the mutations at 2
      specific locations of the ANTXR1 gene by TaqMan(r)-based real-time PCR. The CC
      genotype (p = 0.018) of rs4527238 and the TT genotype (p = 0.048) of rs35685045
      of ANTXR1 were found to be significantly associated with low HbF expression. The
      frequency of the CC genotype of rs4527238 was observed to be high in the low HbF
      patient group compared to the high HbF group (p = 0.009). Likewise, the frequency
      of the TT genotype of rs35685045 was also high among the low HbF group (p =
      0.017). The ANTXR1 genetic mutations and the association with HbF expression in
      the Arab-Indian haplotype sickle cell patients revealed that the ANTXR1 gene may
      be a major HbF modulator leading to potential therapeutic options that should be
      further explored.

PMID- 30114698
TI  - The Role of the Acute Octreotide Suppression Test in Detecting Patients with
      Neuroendocrine Neoplasms.
AB  - BACKGROUND: Serum chromogranin A (CgA) is routinely used as a biomarker in
      patients with neuroendocrine neoplasms (NENs). Several conditions and
      comorbidities may be associated with falsely elevated CgA, often leading to
      extensive diagnostic evaluation, which may be costly and harmful. The aim of this
      study was to analyze the effectiveness of the acute octreotide suppression test
      (AOST) in differentiating falsely elevated serum CgA. METHODS: Our prospective
      study enrolled 45 patients from two different patient cohorts: (1) 29 patients
      with suspicion or presence of NENs (extensive workup and subsequent biopsy
      confirmed 16 NENs); (2) 16 consecutive patients admitted via the Emergency
      Department without NENs (non-NENs). AOST was performed after an overnight fast.
      Baseline CgA was measured, after which 0.25 mg of octreotide was administered
      subcutaneously. CgA was measured 3 and 6 h after administration. RESULTS:
      Baseline CgA levels were similar in NENs and non-NENs. At the end of the AOST,
      CgA decreased by a median of 83.3% (41.0-127.4) in non-NENs and 13.8% (0.0-43.6)
      in NENs (p < 0.001). In patients with increased baseline CgA, a decrease in CgA
      at the 6th hour of < 51.3% had 90.0% sensitivity and 88.9% specificity in
      detecting NENs. In patients with normal baseline serum CgA, a decrease in CgA at
      the 3rd hour of < 17.6% had 83.3% sensitivity and 81.8% specificity in detecting
      patients with NENs. The diagnostic accuracy of the AOST in the entire study
      population was 86.7%. CONCLUSIONS: AOST is a promising tool to increase the
      diagnostic accuracy of serum CgA.

PMID- 30114699
TI  - Spontaneous Viral Clearance in Sixteen HIV-Infected Patients with Chronic
      Hepatitis C.
AB  - BACKGROUND/AIMS: Spontaneous viral clearance of the chronic hepatitis C virus
      (HCV) in human immunodeficiency virus (HIV)-infected patients is a rare event. We
      aimed to identify the clinical, therapeutic, demographic, and laboratory features
      associated with spontaneous HCV clearance in 16 HIV-infected patients with
      chronic hepatitis C (CHC, the largest case series, to our knowledge). METHODS:
      This case series study reports the findings from 16 HIV/HCV coinfected patients
      with CHC who experienced spontaneous clearance of HCV infection. Patients were
      monitored between 2000 and 2013 in the Infectious Diseases Outpatient Clinic at
      the Centro Hospitalar S. Joao, Porto, Portugal. RESULTS: Apart from
      antiretroviral therapy (ART), all patients were also consuming other potential
      hepatotoxic drugs (e.g., alcohol, illicit drugs, methadone, and antituberculosis
      medication). In all but 1 of the 16 HIV-infected patients with CHC, viral
      remission was associated with a temporary suspension of the ART. All patients
      showed a sustained HCV viral clearance. CONCLUSION: A possible drug-induced liver
      injury and/or suspension of ART may, in some cases, contribute to increasing the
      chances of spontaneous HCV clearance in HIV-infected patients with CHC.

PMID- 30114700
TI  - Spontaneous Keloids: A Literature Review.
AB  - BACKGROUND: Keloids are benign fibroproliferative tumors that extend beyond the
      original wound. Spontaneous keloids are those that result without a significant
      history of trauma. There are multiple reported cases in the literature.
      OBJECTIVE: This article provides a summary and review of the cases that have been
      reported with spontaneous keloids and organizes them according to their
      associated medical conditions. METHODS: A literature review was conducted using
      PubMed and MEDLINE that included all English published cases and case series from
      May 1955 to February 2018. RESULTS: Spontaneous keloids have been reported mainly
      in association with syndromes such as Rubinstein-Taybi syndrome, Dubowitz
      syndrome, Noonan syndrome, Goeminne syndrome, Bethlem myopathy,
      conjunctivocorneal dystrophy, X-linked recessive polyfibromatosis and a novel X
      linked syndrome with flamin A mutation. Furthermore, spontaneous keloids were
      reported in atopic patients and a couple of patients who are medically healthy.
      CONCLUSION: Spontaneous keloids are diagnosed clinically based on the patient's
      history, and it is challenging to confirm since they might be triggered by
      minimal injury or inflammation especially if it is a single lesion. Reported
      syndromes indicate a genetic possibility in the pathogenesis of spontaneous
      keloids.

PMID- 30114702
TI  - Reproducibility and Clinical Correlates of Supine Diaphragmatic Motion Measured
      by M-Mode Ultrasonography in Healthy Volunteers.
AB  - BACKGROUND: Assessing diaphragm mobility is important to detect malfunctions or
      impending exhaustion and to evaluate the effects of many chest and abdominal
      conditions on respiratory mechanics. Amongst several imaging methods,
      ultrasonography represents the only noninvasive, nonionizing imaging technique
      widely available for the direct assessment of diaphragm excursion. OBJECTIVES:
      the aim of this study is to prospectively assess the supine diaphragmatic motion
      amplitude, intra- and inter-observer agreement, and anthropometric correlates of
      diaphragm motion variability, measured through M-mode ultrasonography, in a
      sample of healthy volunteers. METHODS: One-hundred healthy volunteers were
      considered eligible for the study. Instead of B-mode imaging, the M-mode
      technique was used to achieve a more accurate measurement of diaphragm motion. To
      assess intra-observer variability, 3 consecutive measurements (M-mode and B-mode)
      of the right dome motion were obtained at every session. To test for inter-rater
      reliability, the subjects were asked to provide 2 more diaphragm motion
      measurements every week, each performed by 2 experienced operators, and 42
      subjects accepted. RESULTS: Diaphragmatic motion was positively correlated with
      height and weight both at quiet (Spearman's coefficient = 0.514, p < 0.001 and
      0.314, p = 0.038) and deep breathing (Spearman's coefficient = 0.342, p = 0.001
      and 0.225, p = 0.024, respectively) and negatively correlated with age, but only
      during deep breathing (Spearman's coefficient = -0.272, p = 0.006). Intra
      observer agreement degree on all 3 measurements was excellent during both quiet
      and deep breathing, with a Cronbach's alpha of 0.793 and 0.901, respectively, and
      an intra-class coefficient of 0.797 and 0.900, respectively. Similarly, the
      degree of inter-observer agreement achieved a Cronbach's alpha of 0.638 and
      0.776, and an inter-class coefficient of 0.632 and 0.778, respectively. Deep
      breathing was associated with sex only in linear multivariable models (B = 
      10.14; 95% confidence interval [CI] -17.86, -2.41; p = 0.011), while quiet
      breathing resulted to be affected by height only (B = 30.05; 95% CI 0.79-59.31; p
      = 0.044). CONCLUSIONS: Diaphragm excursion measurements using the M-mode
      technique were accurate and could be reproduced also when obtained in recumbent
      patients. After adjustments, the main predictors of diaphragmatic motion were sex
      and height, which should be considered to design a specifically tailored study
      and to develop normality reference equations.

PMID- 30114701
TI  - Anti-Cancer Effects of Radix Angelica Sinensis (Danggui) and N
      Butylidenephthalide on Gastric Cancer: Implications for REDD1 Activation and mTOR
      Inhibition.
AB  - BACKGROUND/AIMS: Radix Angelica Sinensis (danggui in Chinese) is widely used in
      traditional chinese medicine (TCM). N-butylidenephthalide (BP), a bioactive
      compound in danggui, is a potential antitumor agent for various cancer types.
      However, its clinical effect and mechanism in the treatment of gastric cancer
      remain undetermined. METHODS: The in vivo protective effect of danggui in
      patients with gastric cancer were validated using data from Taiwan's National
      Health Insurance Research Database (NHIRD). The genes induced by BP-treatment
      were analyzed by whole transcriptome RNA sequencing (RNA-seq) and validated by
      real-time PCR, western blot and siRNA transfection. The effect of BP on AGS cell
      migration and invasion was evaluated in transwell assays. The antitumor effects
      of BP were evaluated in vivo in an AGS xenograft animal model. RESULTS: Danggui
      users were found to have an increased survival rate when compared with danggui
      nonusers (log-rank test p = 0.002) . The use of danggui highly associated with
      decreased mortality (the adjusted hazard ratio (HR) of danggui user was 0.72 [95
      % CI, 0.57-0.92] (p = 0.009). The in vitro results showed that BP inhibited
      gastric cancer cell proliferation, and triggered cellular apoptosis depending on
      the activation of mitochondrial apoptotic pathway. Using RNA-seq analysis we
      found that REDD1 was the highest transcript induced by BP in gastric cancer
      cells. BP induce an increase of REDD1 expression that inhibits mTOR signaling,
      thus inhibiting gastric cancer growth. We used RNA interference to demonstrate
      that the knock-down of REDD1 attenuated the BP-induced mTORC1 activation and
      growth inhibition. BP suppressed the growth of AGS xenografts tumor in vivo.
      CONCLUSION: Danggui can prolong the survival rate of gastric cancer patients in
      Taiwan. BP caused gastric cancer cell death through the activation of
      mitochondria-intrinsic pathway and induced the REDD1 expression leading to mTOR
      signal pathway inhibition in gastric cancer cells. BP inhibited the in vivo
      growth of AGS xenograft tumors. These results may provide the basis for a new
      therapeutic approach toward the treatment of gastric cancer progression.

PMID- 30114703
TI  - Faecal Particle Size in Free-Ranging Proboscis Monkeys, Nasalis larvatus:
      Variation between Seasons.
AB  - Reducing the size of food particles is crucial for herbivores. Seasonal dietary
      changes are known to influence animals' chewing efficiency. Proboscis monkeys
      (Nasalis larvatus) are foregut fermenters, with a high chewing efficiency
      allowing them to achieve very fine faecal particles. In this study, we
      investigated how proboscis monkeys' chewing efficiency varies between wet and dry
      seasons, hypothesising differences possibly related to diet change. Faecal
      particle size analysis is an established approach to estimate chewing efficiency
      in mammalian herbivores. We analysed 113 proboscis monkey faecal samples
      collected in the Lower Kinabatangan Wildlife Sanctuary, between 2015 and 2017. By
      following standard sieve analysis protocols, we measured a mean particle size
      MPS0.025-8 of 0.45 +/- 0.14 mm, and confirmed a previous result that proboscis
      monkeys have a very low faecal MPS. This study highlights a seasonal influence on
      proboscis monkeys' chewing efficiency, with smaller MPS (better chewing
      efficiency) during the wet season. During that time of the year, individuals may
      potentially change their diet, as all faecal samples contained intact seeds.
      Whether the seasonal MPS difference in proboscis monkeys is smaller than in other
      colobines due to their "rumination" strategy remains to be investigated.

PMID- 30114704
TI  - PCI29732, a Bruton's Tyrosine Kinase Inhibitor, Enhanced the Efficacy of
      Conventional Chemotherapeutic Agents in ABCG2-Overexpressing Cancer Cells.
AB  - BACKGROUND/AIMS: Multidrug resistance (MDR) induced by the ABC transporter
      subfamily B member 1 (ABCB1) and subfamilyG member 2 (ABCG2) limits successful
      cancer chemotherapy and no commercially available MDR modulator is used in the
      clinic. In the current study, we aimed to investigate the effects of PCI29732 on
      the enhancement of chemotherapeutic agents. METHODS: Cell cytotoxicity and
      reversal effect were measured with MTT assay. Additionally, flow cytometry was
      employed to detect the accumulation and efflux of the drugs. We investigated the
      interaction of PCI29732 and the substrate binding sites of ABCG2 was investigated
      via the photo-labeling of ABCG2 with the [125I] iodoarylazidoprazosin. The
      vanadate-sensitive ATPase activity of ABCG2 was measured to identify whether the
      drug affected the ATPase activity. RT-PCR and Western blot were utilized to
      analyze mRNA and protein expression respectively. RESULTS: Here, we found that
      PCI29732 significantly enhanced the efficacy of substrate chemotherapeutic agents
      in ABCG2-overexpressing cells and also in xenografts harboring the H460/MX20 cell
      that overexpress ABCG2, but not in their parental sensitive cells and ABCB1
      overexpressing cells. Mechanistically, the intracellular accumulations of
      doxorubicin and Rhodamine 123 were increased in ABCG2-overexpressing S1-MI-80
      cells with the presence of PCI29732. PCI29732 stimulated the ATPase activity of
      ABCG2 at low concentrations. However at the high concentrations, PCI29732
      inhibited the ATPase activity, and competed with [125I]-iodoarylazidoprazosin for
      photo-affinity labeling of ABCG2. PCI29732 did neither alter the mRNA or protein
      expression levels of ABCG2 nor the phosphorylation levels of AKT and ERK1/2.
      CONCLUSION: Our study demonstrates that PCI29732 inhibits the function of ABCG2
      by competitively binding to the ATP-binding site of ABCG2 and enhances the anti
      tumor efficacy of substrate chemotherapeutic agents, This findings encourages the
      development of combinational chemotherapy for the treatment of ABCG2-
      overexpressing cancer patients.

PMID- 30114706
TI  - Extracorporeal Membrane Oxygenation in Predominantly Leuco- and Thrombocytopenic
      Haematologic/Oncologic Patients with Acute Respiratory Distress Syndrome - a
      Single-Centre Experience.
AB  - AIMS: The acute respiratory distress syndrome (ARDS) is a frequent condition
      following pneumonia in immunocompromised cancer patients. Extracorporeal membrane
      oxygenation (ECMO) may serve as a rescue therapy in refractory ARDS but has still
      not been studied in predominantly leuco- and thrombocytopenic cancer patients.
      PATIENTS AND METHODS: In this monocentric, retrospective, observational study, we
      assessed all cancer patients treated with ECMO for ARDS between 2013 and 2017.
      RESULTS: 25 patients, 11 of whom underwent haematopoietic stem cell
      transplantation (SCT), were analysed. The main reason for ARDS was pneumonia in
      72%. All patients were under invasive ventilation at ECMO. All but 9/3 patients
      suffered from leuco-/thrombocytopenia due to anti-cancer treatment or underlying
      disease. Overall, 17 patients (68%) died on ECMO, whereas 5 patients survived to
      hospital discharge (20%). All patients after recent allogeneic (allo-)SCT have
      died. 4 patients experienced severe bleeding events. CONCLUSIONS: Discouraging
      survival rates in patients treated after allo-SCT do not support the use of ECMO
      for ARDS in this patient subgroup. On the contrary, cancer patients in at least
      stable disease otherwise eligible for full-code intensive care unit management,
      even those with severe thrombocytopenia, may be potential candidates for ECMO in
      case of severe ARDS failing conventional measures.

PMID- 30114705
TI  - Autophagy and Ubiquitin-Mediated Proteolytic Degradation of PML/Raralpha Fusion
      Protein in Matrine-Induced Differentiation Sensitivity Recovery of ATRA-Resistant
      APL (NB4-LR1) Cells: in Vitro and in Vivo Studies.
AB  - BACKGROUND/AIMS: Although the cure rate of acute promyelocytic leukemia (APL) has
      exceeded 90%, the relapse/refractory APL that resistant to all-trans retinoic
      acid (ATRA) or ATO was still serious concern. Matrine (MAT) could improve the
      differentiation ability of ATRA-resistant APL cells. This study aimed to explore
      how the APL-specific fusion protein was degraded in ATRA-resistant APL with the
      application of MAT and ATRA. METHODS: ATRA-sensitive (NB4) and ATRA-resistant
      (NB4-LR1) cell lines were used. Nitroblue tetrazolium reduction assay and flow
      cytometry were used to detect the differentiation ability. The activity of
      ubiquitin-proteasome and autophagy-mediated pathways in both cells treated with
      ATRA with or without MAT were compared in protein and mRNA level (Western blot
      analysis, qRT-PCR), the Fluorescent substrate Suc-LLVY-AMC detection was used to
      detect the activity of proteasome, and electron microscope for observing
      autophagosome. MG 132(proteasome inhibitor), rapamycin (autophagy activator),
      hydroxychloroquine (lysosomal inhibitor) and STI571 [retinoic acid receptor alpha
      (RARalpha) ubiquitin stabilizer] were used as positive controls. The effect of
      MAT was observed in vivo using xenografts. RESULTS: MAT improved the sensitivity
      of NB4-LR1cells to ATRA treatment, which was consistent with the expression of
      PML-RARalpha fusion protein. MAT promoted the ubiquitylation level in NB4-LR1. MG
      132 induced the decrease in RARalpha in both cell lines, and hampered the
      differentiation of NB4 cells. MAT also promoted the autophagy in NB4-LR1 cells,
      with an increase in microtubule-associated protein 1 light chain3 (LC3)-II and
      LC3-II/LC3-I ratio and exhaustion of P62. The expression of LC3II increased
      significantly in the MAT and ATRA + MAT groups in combination with lysosomal
      inhibitors. A similar phenomenon was observed in mouse xenografts. MAT induced
      apoptosis and differentiation. CONCLUSIONS: Autophagy and ubiquitin-mediated
      proteolytic degradation of PML/RARalpha fusion protein are crucial in MAT-induced
      differentiation sensitivity recovery of NB4-LR1 cells.

PMID- 30114707
TI  - Chartis Measurement of Collateral Ventilation: Conscious Sedation versus General
      Anesthesia - A Retrospective Comparison.
AB  - BACKGROUND: Absence of interlobar collateral ventilation using the Chartis
      measurement is the key predictor for successful endobronchial valve treatment in
      severe emphysema. Chartis was originally validated in spontaneous breathing
      patients under conscious sedation (CS); however, this can be challenging due to
      cough, mucus secretion, mucosal swelling, and bronchoconstriction. Performing
      Chartis under general anesthesia (GA) avoids these problems and may result in an
      easier procedure with a higher success rate. However, using Chartis under GA with
      positive pressure ventilation has not been validated. OBJECTIVES: In this study
      we investigated the impact of anesthesia technique, CS versus GA, on the
      feasibility and outcomes of Chartis measurement. METHODS: We retrospectively
      analyzed all Chartis measurements performed at our hospital from October 2010
      until December 2017. RESULTS: We analyzed 250 emphysema patients (median forced
      expiratory volume in 1 s 26%, range 12-52% predicted). In 121 patients (48%) the
      measurement was performed using CS, in 124 (50%) using GA, and in 5 (2%) both
      anesthesia techniques were used. In total, 746 Chartis readings were analyzed
      (432 CS, 277 GA, and 37 combination). Testing under CS took significantly longer
      than GA (median 19 min [range 5-65] vs. 11 min [3-35], p < 0.001) and required
      more measurements (3 [1-13] vs. 2 [1-6], p < 0.001). There was no significant
      difference in target lobe volume reduction after treatment (-1,123 mL [-3,604 to
      332] in CS vs. -1,251 mL [-3,333 to -1] in GA, p = 0.35). CONCLUSIONS: In
      conclusion, Chartis measurement under CS took significantly longer and required
      more measurements than under GA, without a difference in treatment outcome. We
      recommend a prospective trial comparing both techniques within the same patients
      to validate this approach.

PMID- 30114708
TI  - Orai1 and Stim1 Mediate the Majority of Store-Operated Calcium Entry in Multiple
      Myeloma and Have Strong Implications for Adverse Prognosis.
AB  - BACKGROUND/AIMS: Multiple myeloma (MM) is a plasma cell neoplasm which
      constitutes about 10% of all hematologic malignancies. Despite the development
      and application of novel agents, MM still undergoes an aggressive and incurable
      course in the vast majority of patients. Ca2+ is one of the critical regulators
      of cell migration. Ca2+ influx is essential for the migration of various types of
      cells including tumor cells. However, the role of store-operated calcium entry
      (SOC) channels, the only Ca2+ channels of non-excitable cells, has not yet been
      reported in MM cell survival. METHODS: We evaluated the expression of Stim1 and
      Orai1 (two key regulators of SOC) in MM tissues and cell lines by
      immunohistochemical assay, quantitative real-time PCR assay and western blot. MM
      cell lines were pretreated with pharmacological blockers and siRNAs, and then MM
      cell proliferation, cell cycle arrest, and apoptosis were examined by FACS (flow
      cytometry) assay, and Annexin V-FITC/PI staining. The correlation between the
      expression of Stim1 (or Orai1) level and outcome in MM were assessed by using
      Progress Free Survival (PFS). RESULTS: Stim1 and Orai1 were both abundantly
      expressed in MM tissue and MM cell lines. Inhibition of SOCE reduced MM cell
      viability, and induced cell cycle arrest and apoptosis. Stim1 or Orai1 silencing
      also reduced cell viability, caused cell apoptosis and cell cycle arrest in MM
      cell lines. Over-expression of Stim1/Orai1 in MM patients was closely associated
      with the clinical outcome of MM. CONCLUSION: The Stim1/Orai1-mediated signaling
      participates in the pathogenesis of MM, which represents an attractive target for
      future therapeutic intervention.

PMID- 30114709
TI  - Metabolic Shift Induced by omega -3 PUFAs and Rapamycin Lead to Cancer Cell
      Death.
AB  - BACKGROUND/AIMS: Rapamycin (Rp), the main mammalian target of rapamycin complex
      inhibitor, is a promising therapeutic agent for breast cancer. However, metabolic
      disorders and drug resistance reduce its efficacy. Epidemiological, clinical, and
      experimental studies have demonstrated that omega-3 polyunsaturated fatty acids
      (omega-3 PUFAs) significantly reduce the incidence and mortality of breast cancer
      and improve metabolic disorders. METHODS: Three breast cancer cell lines and
      immunocompetent and immunodeficient mice were used to evaluate the therapeutic
      effects of Rp plus omega-3 PUFA treatment. The production of reactive oxygen
      species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift
      was examined by metabonomics, seahorse experiments, and western blot analysis.
      RESULTS: We found that omega-3 PUFAs and Rp synergistically induced cell cycle
      arrest and apoptosis in vitro and in vivo, accompanied by autophagy blockage. In
      addition, Rp-induced hypertriglyceridemia and hypercholesterolemia were
      completely abolished by omega-3 PUFA supplementation. Moreover, the combined
      treatment of omega-3 PUFA and Rp significantly inhibited glycolysis and glutamine
      metabolism. The anti-tumor effects of this combination treatment were dependent
      on ROS production, which was increased by beta-oxidation and oxidative
      phosphorylation. CONCLUSION: Our study revealed that omega-3 PUFA enhanced the
      anti-tumor activity of Rp while minimizing its side effects in vitro and in vivo.
      These results provide novel insights into the mechanisms underlying the potential
      beneficial effects of Rp combined with omega-3 PUFAs on the prevention of breast
      cancer.

PMID- 30114711
TI  - Contact Lens Health Week - August 20-24, 2018.
AB  - August 20-24, 2018, marks the fifth annual Contact Lens Health Week. In
      collaboration with partners from clinical, public health, industry, and
      regulatory sectors, CDC is promoting healthy contact lens wear and care practices
      to reduce the risk for eye infections among the approximately 45 million persons
      in the United States who wear contact lenses. Research after outbreaks of rare
      but serious eye infections in the United States has indicated that these
      infections occur most often in contact lens wearers who do not take proper care
      of their contact lenses, indicating a need to promote safer wear and care (1,2).

PMID- 30114710
TI  - CD38 Deficiency Protects Heart from High Fat Diet-Induced Oxidative Stress Via
      Activating Sirt3/FOXO3 Pathway.
AB  - BACKGROUND/AIMS: Previous studies showed that CD38 deficiency protected heart
      from ischemia/reperfusion injury and high fat diet (HFD)-induced obesity in mice.
      However, the role of CD38 in HFD-induced heart injury remains unclear. In the
      present study, we have investigated the effects and mechanisms of CD38 deficiency
      on HFD-induced heart injury. METHODS: The metabolites in heart from wild type
      (WT) and CD38 knockout (CD38-/-) mice were examined using metabolomics analysis.
      Cell viability, lactate hydrogenase (LDH) release, super oxide dismutase (SOD)
      activity, reactive oxygen species (ROS) production, triglyceride concentration
      and gene expression were examined by biochemical analysis and QPCR. RESULTS: Our
      results revealed that CD38 deficiency significantly elevated the intracellular
      glutathione (GSH) concentration and GSH/GSSG ratio, decreased the contents of
      free fatty acids and increased intracellular NAD+ level in heart from CD38-/-
      mice fed with HFD. In addition, in vitro knockdown of CD38 significantly
      attenuated OA-induced cellular injury, ROS production and lipid synthesis.
      Furthermore, the expression of mitochondrial deacetylase Sirt3 as well as its
      target genes FOXO3 and SOD2 were markedly upregulated in the H9C2 cell lines
      after OA stimulation. In contrast, the expressions of NOX2 and NOX4 were
      significantly decreased in the cells after OA stimulation. CONCLUSION: Our
      results demonstrated that CD38 deficiency protected heart from HFD-induced
      oxidative stress via activating Sirt3/FOXO3-mediated anti-oxidative stress
      pathway.

PMID- 30114712
TI  - Bilateral Paravertebral Block versus Thoracic Epidural Analgesia for Pain Control
      Post-Cardiac Surgery: A Randomized Controlled Trial.
AB  - BACKGROUND:  Adequate pain control after cardiac surgery is essential.
      Paravertebral block is a simple technique and avoids the potential complications
      of epidural catheters. The objective of this study is to compare the effect of
      ultrasound-guided bilateral thoracic paravertebral block with thoracic epidural
      block on pain control after cardiac surgery. MATERIALS AND METHODS:  Between
      March 2016 and 2017, 145 patients who had cardiac surgery through median
      sternotomy were randomized by stratified blocked randomization into two groups.
      Group I (n = 70 patients) had bilateral ultrasound-guided thoracic paravertebral
      block and Group II (n = 75 patients) had thoracic epidural analgesia. The primary
      end point was the postoperative visual analogue scale (VAS). The duration of
      mechanical ventilation, intensive care unit (ICU), and hospital stay were the
      secondary end points. The study design is a randomized parallel superiority
      clinical trial. RESULTS:  Both groups had similar preoperative and operative
      characteristics. No significant difference in VAS measured immediately after
      endotracheal extubation then after 12, 24, and 48 hours between groups (p =
      0.45). Pain score significantly declined with the repeated measures (p < 0.001)
      and the decline was not related to the treatment group. Postoperative pain was
      significantly related to diabetes mellitus (p = 0.039). Six patients in group I
      (8.5%) required an additional dose of morphine versus three patients (4%) in
      group II (p = 0.30). Patients in group I had significantly shorter ICU stay (p =
      0.005) and lower incidence of urinary retention (p = 0.04) and vomiting (p =
      0.018). No difference was found in operative complications between groups.
      CONCLUSION:  This randomized parallel controlled trial demonstrates that
      ultrasound-guided paravertebral block is safe and effective method for relieving
      post-cardiac surgery sternotomy pain compared with thoracic epidural analgesia
      but not superior to it.

PMID- 30114713
TI  - Acute Effect of Mitral Valve Repair on Mitral Valve Geometry.
AB  - BACKGROUND:  The aim of this study was to quantify acute mitral valve (MV)
      geometry dynamic changes throughout the cardiac cycle using three-dimensional
      transesophageal echocardiography (3D TEE) in patients undergoing surgical MV
      repair (MVR) with ring annuloplasty and optional neochord implantation. METHODS: 
      Twenty-nine patients (63 +/- 10 years) with severe primary mitral regurgitation
      underwent surgical MVR using ring annuloplasty with or without neochord
      implantation. We recorded 3D TEE data throughout the cardiac cycle before and
      after MVR. Dynamic changes (4D) in the MV annulus geometry and anatomical MV
      orifice area (AMVOA) were measured using a novel semiautomated software (Auto
      Valve, Siemens Healthcare). RESULTS:  MVR significantly reduces the
      anteroposterior diameter by up to 38% at end-systole (36.8-22.7 mm; p < 0.001)
      and the lateromedial diameter by up to 31% (42.7-30.3 mm; p < 0.001). Moreover,
      the annular circumference was reduced by up to 31% at end-systole (129.6-87.6 mm,
      p < 0.001), and the annular area was significantly decreased by up to 52% (12.8
      5.7 cm2; p < 0.001). Finally, the AMVOA experienced the largest change,
      decreasing from 1.1 to 0.2 cm2 during systole (at midsystole; p < 0.001) and from
      4.1 to 3.2 cm2 (p < 0.001) during diastole. CONCLUSIONS:  MVR reduces the annular
      dimension and the AMVOA, contributing to mitral competency, but the use of
      annuloplasty rings reduces annular contractility after the procedure. Surgeons
      can use 4D imaging technology to assess MV function dynamically, detecting the
      acute morphological changes of the mitral annulus and leaflets before and after
      the procedure.

PMID- 30114714
TI  - Minimally Invasive Redo-Aortic Valve Replacement: Reduced Operative Times as
      Compared to Full Sternotomy.
AB  - OBJECTIVES:  Increasing experience with minimally invasive cardiac (MIC) aortic
      valve (AV) replacement makes AV reoperations (rAVR) an appealing alternative to
      conventional redo surgery. The aim of the study was to compare the perioperative
      outcome after isolated MIC versus full-sternotomy (FS) rAVR. METHODS:  We
      retrospectively analyzed data of 116 patients from three centers who underwent
      rAVR by using a FS (n = 70, 60.3%) or a partial upper sternotomy approach (n =
      46, 39.7%). Both groups were compared in terms of 30-day mortality by using
      binary-logistic regression models. Further the EuroSCORE II was used to adjust
      for preoperative conditions in a multivariable model. Perioperative times and
      complications were compared between the two groups. RESULTS:  There was no
      statistically significant difference in perioperative mortality between FS (n =
      5, 7.1%) and MIC (n = 1, 2.2%) rAVR in the original population (odds ratio [OR]
      3.462, 95% confidence interval [CI] 0.391-30,635, p = 0.264) and after adjusting
      for EuroSCORE II (OR 2.759, 95% CI 0.298-25.567, p = 0.372). Cardiopulmonary
      bypass- (115.5 minutes vs. 137.5 minutes, p = 0.070) and cross-clamp times (69.0
      minutes vs. 81.0 minutes, p = 0.028) were reduced in the MIC group. There was a
      lower prevalence of postoperative renal failure requiring renal replacement
      therapy (RRT) in the MIC group 0 and 8.6% (p = 0.041), respectively. No
      differences were detected between the groups regarding postoperative
      complications. CONCLUSION:  MIC rAVR is associated with reduced cardiopulmonary
      and cross-clamp times as well as the need for RRT as compared with FS. MIC-rAVR
      seems to be a viable option in surgical candidates for AV reoperations.

PMID- 30114715
TI  - Is the Freedom SOLO Stentless Bioprosthesis a Useful Tool for Patients with
      Aortic Endocarditis and Aortic Annular Destruction?
AB  - BACKGROUND:  The Freedom SOLO (FS) stentless bovine-pericardial prosthesis with a
      supra-annular implantation technique can be a viable option for patients with
      endocarditic annular destruction. We assessed early- and long-term outcomes
      following the use of this prosthesis in extensive aortic valve endocarditis.
      METHODS:  From 2006 to 2016, 59 patients with extensive aortic endocarditis
      underwent aortic valve replacement (AVR) with FS (cumulative follow-up 263
      patients-years) in three European centers; all patients presented annular tissue
      infection, while 54.3% of patients had annular abscess. RESULTS:  Mean age was 66
      +/- 11 years and mean EuroSCORE I was 30.3% (standard deviation: 24.1%). In our
      series, 30.5% of patients had prosthetic valve endocarditis. Early mortality was
      15.2% (nine patients). Estimated overall survival at 5 and 10 years was 68.9%
      (95% confidence interval [CI]: 62.8-75.0%) and 59.1% (95% CI: 66.8-81.2%),
      respectively. At 10-year survival, freedom from valve-related death was 83.7%
      (95% CI: 80.9-86.5%). No structural valve deterioration was reported in this
      series. Five patients (8.5%) had recurrent endocarditis during follow-up and two
      of them underwent reoperation. Survival freedom from reoperation and endocarditis
      at 10-year follow-up was 88.0% (CI: 80.4-95.6%) and 86.7% (CI: 80.5-92.9%),
      respectively. CONCLUSION:  FS stentless bioprosthesis is a valuable and simple
      option to achieve AVR in patients with extensive aortic annulus endocarditis.
      Although in this group of complex patients, early mortality remains considerably
      high, late survival outcomes are comparable to the more technically demanding
      homografts and conventional stentless bioprostheses, with low rates of
      endocarditis recurrence.

PMID- 30114716
TI  - Meta-analysis of Valve-in-Valve Transcatheter versus Redo Surgical Aortic Valve
      Replacement.
AB  - OBJECTIVE:  The objective of this study was to determine whether valve-in-valve
      transcatheter aortic valve implantation (VIV-TAVI) is associated with better
      survival than redo surgical aortic valve replacement (SAVR) in patients with
      degenerated aortic valve bioprostheses, and we performed a meta-analysis of
      comparative studies. METHODS:  To identify all comparative studies of VIV-TAVI
      versus redo SAVR; MEDLINE, Embase, and the Cochrane Central Register of
      Controlled Trials were searched through October 2017. For each study, data
      regarding all-cause mortality in both the VIV-TAVI and redo SAVR groups were used
      to generate odds ratios (ORs). To assess selection bias, we generated ORs and
      (standardized) mean differences (MDs) for baseline characteristics. Study
      specific estimates were combined in the random-effects model. RESULTS:  Of 446
      potentially relevant articles screened initially, 6 reports of retrospective
      comparative studies enrolling a total of 498 patients were identified. Pooled
      analyses of baseline characteristics demonstrated no statistically significant
      differences in the proportion of women, patients with diabetes mellitus, patients
      with coronary artery disease, and patients with baseline New York Heart
      Association functional class of >=III; baseline ejection fraction; and predicted
      mortality between the VIV-TAVI and redo SAVR groups. Patients in the VIV-TAVI
      group, however, were significantly older (MD, 4.20 years) and had undergone prior
      coronary artery bypass grafting more frequently (OR, 2.19) than those in the redo
      SAVR group. Main pooled analyses demonstrated no statistically significant
      differences in early (30 days or in-hospital) (OR, 0.91; p = 0.83) and midterm
      (180 days-3 years) all-cause mortalities (OR, 1.42; p = 0.21) between the VIV
      TAVI and redo SAVR groups. CONCLUSION:  In patients with degenerated aortic valve
      bioprostheses, especially elderly or high-risk patients, VIV-TAVI could be a
      safe, feasible alternative to redo SAVR. The lack of randomized data and
      differences in baseline characteristics in the present analysis emphasize the
      need for prospective randomized trials.

PMID- 30114717
TI  - Preoperative Assessment of Coronary Arteries by Cardiac Computed Tomography in
      Patients with Lung Cancer.
AB  - BACKGROUND:  To retrospectively evaluate characteristics of coronary artery
      disease (CAD) in patients undergoing lung resection for cancer by using dual
      source computed tomography (DSCT), thus increasing our understanding of
      perioperative evaluation. METHODS:  DSCT coronary angiography was performed for
      perioperative evaluation in 145 patients with non-small cell lung cancer (NSCLC)
      due to suspected CAD. The imaging characteristics of CAD including extent,
      distribution and types of plaques, and luminal stenosis and congenial anomalous
      including origin of coronary arteries and myocardial bridge (MB) were evaluated
      and compared by sex, smoking behavior, and pathological types. RESULTS:  In
      total, coronary artery plaques were observed in 130 (89.7%) patients. A total of
      205 coronary vessels (1.7 +/- 1.3 per patient) and 278 segments (2.4 +/- 2.3 per
      patient) were found to have plaques, respectively. The most frequently involved
      segment were the left anterior descending (LAD) artery (45.4%) and its proximal
      segment (24.1%) (p < 0.05). Mild narrowing (61.7%) and calcified plaques (52.9%)
      were most found (all p < 0.001). Types of plaques, luminal narrowing and extent
      were not significantly different by sex, smoking behavior, or pathological type.
      Anomalous origination of the right coronary ostium from left sinus was observed
      in 0.7% of patients. MB was observed in 16.6% of patients. CONCLUSION:  Dual
      source CT is a useful preoperative noninvasive test for CAD in patients planning
      to undergo lung resection for cancer.

PMID- 30114718
TI  - Platelet Function or Genetic Testing for Guiding De-Escalation of Anti-Platelet
      Therapy: The Jury is Still Out.

PMID- 30114719
TI  - HTRA2 Defect: A Recognizable Inborn Error of Metabolism with 3-Methylglutaconic
      Aciduria as Discriminating Feature Characterized by Neonatal Movement Disorder
      and Epilepsy-Report of 11 Patients.
AB  - Neonatal-onset movement disorders, especially in combination with seizures, are
      rare and often related to mitochondrial disorders. 3-methylglutaconic aciduria (3
      MGA-uria) is a marker for mitochondrial dysfunction. In particular, consistently
      elevated urinary excretion of 3-methylglutaconic acid is the hallmark of a small
      but growing group of inborn errors of metabolism (IEM) due to defective
      phospholipid remodeling or mitochondrial membrane-associated disorders (mutations
      in TAZ, SERAC1, OPA3, CLPB, DNAJC19, TMEM70, TIMM50). Exome/genome sequencing is
      a powerful tool for the diagnosis of the clinically and genetically heterogeneous
      mitochondrial disorders. Here, we report 11 individuals, of whom 2 are previously
      unpublished, with biallelic variants in high temperature requirement protein A2
      (HTRA2) encoding a mitochondria-localized serine protease. All individuals
      presented a recognizable phenotype with neonatal- or infantile-onset
      neurodegeneration and death within the first month of life. Hallmark features
      were central hypopnea/apnea leading to respiratory insufficiency, seizures,
      neutropenia, 3-MGA-uria, tonus dysregulation, and dysphagia. Tremor, jitteriness,
      dystonia, and/or clonus were also common. HTRA2 defect should be grouped under
      the IEM with 3-MGA-uria as discriminating feature. Clinical characteristics
      overlap with other disorders of this group suggesting a common underlying
      pathomechanism. Urinary organic acid analysis is a noninvasive and inexpensive
      test that can guide further genetic testing in children with suggestive clinical
      findings.

PMID- 30114720
TI  - [Interface Problems Between Inpatient, GP and Outpatient Specialist Care:
      Viewpoint of General Practitioners in Dresden].
AB  - OBJECTIVES: The aim of the study was to identify interface problems between
      inpatient, GP and outpatient specialist care from the perspective of general
      practitioners in Dresden, especially in older multimorbid patients. METHODS: The
      data were collected in the context of the pilot study "Multimedication and its
      Consequences for the Primary Care of Patients in Saxony" and included guided
      interviews with 7 general practitioners. The interviews were transcribed and
      analyzed according to the inductive content analysis of Mayring. RESULTS: At the
      interface of inpatient to outpatient care, several problems regarding discharge
      management, intersectoral communication and cooperation as well as in the
      management of medication were found. Concerning the interface between general
      practitioners and outpatient specialist care, problems were particularly marked
      with regard to free choice of doctors, appointment management, medical decision
      making process, medication management as well as the use of the electronic health
      card. Regardless of the interfaces, the lack of communication could be worked out
      as a central challenge. CONCLUSION: There are several problems with all adjacent
      interfaces. What is striking here is the lack of communication and cooperation
      between all parties involved. Possible causes were the often very different
      working methods and framework conditions, human and material resources and
      therapeutic intentions and approaches between the different interfaces. One
      possible approach to improve the situation may be the law regarding secure
      digital communications and healthcare applications, which exists since 2016.
      Among other things, it promises a secure and rapid inter- and intrasectoral
      exchange of patient data. The overall goal of healthcare in Germany should be an
      optimized and process-oriented interface management in order to ensure a secure
      and seamless sectoral transition to patients.

PMID- 30114722
TI  - Generation of Pancreatic beta-cells From iPSCs and their Potential for Type 1
      Diabetes Mellitus Replacement Therapy and Modelling.
AB  - Diabetes type 1 (T1D) is a common autoimmune disease characterized by permanent
      destruction of the insulin-secreting beta-cells in pancreatic islets, resulting
      in a deficiency of the glucose-lowering hormone insulin and persisting high blood
      glucose levels. Insulin has to be replaced by regular subcutaneous injections,
      and blood glucose level must be monitored due to the risk of hyperglycemia.
      Recently, transplantation of new pancreatic beta-cells into T1D patients has come
      to be considered one of the most potentially effective treatments for this
      disease. Therefore, much effort has focused on understanding the regulation of
      beta-cells. Induced pluripotent stem cells (iPSCs) represent a valuable source
      for T1D modelling and cell replacement therapy because of their ability to
      differentiate into all cell types in vitro. Recent advances in stem cell-based
      therapy and gene-editing tools have enabled the generation of functionally adult
      pancreatic beta-cells derived from iPSCs. Although animal and human pancreatic
      development and beta-cell physiology have significant differences, animal models
      represent an important tool in evaluating the therapeutic potential of iPSC
      derived beta-cells on type 1 diabetes treatment. This review outlines the recent
      progress in iPSC-derived beta-cell differentiation methods, disease modelling,
      and future perspectives.

PMID- 30114721
TI  - Electrical Stimulation to the Infraspinatus on Hypertrophy and Strength of the
      Shoulder.
AB  - The purpose of this study was to determine the effects of six weeks of electrical
      muscle stimulation (EMS) on the strength and muscle mass of the infraspinatus
      muscle. Twenty non-athletes (age: 24+/-3.4 years, height: 171.5+/-5.6 cm, mass:
      65.2+/-8.1 kg) were randomly classified into two groups, an electrical muscle
      stimulation group (EMS group) and a control group (CON group). The EMS group
      completed a total of 18 20- min EMS sessions, three times per week over a period
      of six weeks, while the CON group received no intervention. The muscle
      thicknesses of both the infraspinatus and the deltoid muscles, the cross
      sectional area (CSA) of the whole infraspinatus muscle, and the isometric and
      isokinetic peak torques of shoulder external rotations were measured before and
      after intervention. It was found that the muscle thickness of the superior
      infraspinatus (Pre 0.92+/-0.19 cm2, Post 0.99+/-0.16 cm2, p=0.02) and the CSA
      (Pre 10.99+/-1.32 cm2, Post 11.99+/-1.02 cm2, p=0.03) significantly increased in
      the EMS group. This study demonstrated that EMS of the infraspinatus muscle over
      a period of six weeks resulted in hypertrophy of the infraspinatus muscle.

PMID- 30114723
TI  - [Fundamental Changes in the Treatment of Lung Cancer].
AB  - In recent years, the diagnosis and medical treatment of lung cancer patients has
      been changed profoundly. Still being a deadly disease for most patients, new
      developments in treatment approaches and therapy selection lead to significantly
      extended duration of disease control and overall survival. This development is
      evident not only in medical issues but also comprises various political and
      organisational aspects. These aspects will be briefly characterised and discussed
      in the following.

PMID- 30114724
TI  - Tetralogy of Fallot with mesocardia with dual hepatic venous drainage.

PMID- 30114725
TI  - Conjunctival ultraviolet autofluorescence area, but not intensity, is associated
      with myopia.
AB  - BACKGROUND: Conjunctival ultraviolet autofluorescence (CUVAF) has been used as a
      biomarker of time spent outdoors. Smaller CUVAF area is associated with myopia in
      southern hemisphere cohorts. Further research is required to determine if this
      association is replicated in northern latitudes and whether average CUVAF
      intensity is a valuable metric. This prospective study explored the association
      between myopia, CUVAF (area and intensity) and additional indicators of sun
      exposure (vitamin D3 and self-reported sun exposure preferences) across seasons
      at a location of 55 degrees  north. METHODS: Young adults (age 18-20) provided
      blood samples biannually (March/April and September/October) over an 18-month
      period (four phases) for the assessment of 25-hydroxyvitamin D (25(OH)D3 )
      concentrations (liquid chromatography-tandem mass spectrometry). CUVAF (total
      area, average intensity) and self-reported sun exposure preferences were recorded
      at each phase. Axial length and corneal radius were measured. Refractive error
      was measured by autorefractor and spherical equivalent refraction used to
      classify participants into refractive groups: myopic (spherical equivalent
      refraction <= -0.50 DS) or non-myopic. RESULTS: Fifty-four participants (24
      myopes, 30 non-myopes) participated. CUVAF area was negatively associated with
      the presence of myopia (odds ratio = 0.94, 95 per cent confidence interval = 0.90
      0.98, p = 0.002). Myopes = 4.5 mm2 (interquartile range [IQR] 0.95-6.4 mm2 ), non
      myopes = 7.0 mm2 (IQR = 2.0-10.7 mm2 ). No significant association was found
      between CUVAF intensity and refractive group (p = 0.17). There was no significant
      association between sun exposure preferences or serum concentration of 25(OH)D3
      and refractive status (all p >= 0.21). CUVAF measures were not associated with
      ocular biometry measures (all p >= 0.084). CUVAF area was unaffected by season
      (all p >= 0.45) and variations in CUVAF area over the study period did not exceed
      the repeatability of the measurement technique. CONCLUSION: Myopia was associated
      with smaller areas of CUVAF indicative of less cumulative ultraviolet-B exposure.
      These findings suggest that CUVAF measures are a useful, non-invasive biomarker
      of the time spent outdoors in adults in northern hemisphere populations.

PMID- 30114726
TI  - Total observed caries experience: assessing the effectiveness of community-based
      caries prevention.
AB  - OBJECTIVES: To compare common measures for dental caries in longitudinal caries
      research in support of a new measure, the Total Observed Caries Experience
      (TOCE). METHODS: TOCE was calculated as the total number of decayed or filled
      teeth ever observed. TOCE was compared to dmft, DMFT, and the prevalence of
      untreated decay using data from a 4-year, cluster randomized community-based
      caries prevention program. Outcomes were analyzed using generalized estimating
      equations and assessed change over time and effects across treatment groups.
      RESULTS: For TOCE and DMFT, the risk of caries over time increased. In contrast,
      risks decreased for dmft and the prevalence of untreated decay, driven largely by
      decayed primary teeth being exfoliated. Effects across treatment groups showed
      increased risk for some outcomes and attenuated risks in others; however,
      treatment effects for TOCE were more in line with expected results when compared
      with controls. CONCLUSIONS: TOCE accounts for caries on primary and permanent
      dentition and is not subject to bias due to exfoliation. It can be used as a
      robust measure to evaluate community-based caries prevention programs.

PMID- 30114727
TI  - Association of changes in inflammation with variation in glycaemia, insulin
      resistance and secretion based on the KORA study.
AB  - AIMS: Subclinical systemic inflammation may contribute to the development of type
      2 diabetes, but its association with early progression of glycaemic deterioration
      in persons without diabetes has not been fully investigated. Our primary aim was
      to assess longitudinal associations of changes in pro-inflammatory (leukocytes,
      high-sensitivity C-reactive protein (hsCRP)) and anti-inflammatory (adiponectin)
      markers with changes in markers that assessed glycaemia, insulin resistance, and
      secretion (HbA1c , HOMA-IR, and HOMA-beta). Furthermore, we aimed to directly
      compare longitudinal with cross-sectional associations. MATERIALS AND METHODS:
      This study includes 819 initially nondiabetic individuals with repeated
      measurements from the Cooperative Health Research in the Region of Augsburg
      (KORA) S4/F4 cohort study (median follow-up: 7.1 years). Longitudinal and cross
      sectional associations were simultaneously examined using linear mixed growth
      models. Changes in markers of inflammation were used as independent and changes
      in markers of glycaemia/insulin resistance/insulin secretion as dependent
      variables. Models were adjusted for age, sex, major lifestyle and metabolic risk
      factors for diabetes using time-varying variables in the final model. RESULTS:
      Changes of leukocyte count were positively associated with changes in HbA1c and
      HOMA-beta while changes in adiponectin were inversely associated with changes in
      HbA1c . All examined cross-sectional associations were statistically significant;
      they were generally stronger and mostly directionally consistent to the
      longitudinal association estimates. CONCLUSIONS: Adverse changes in low-grade
      systemic inflammation go along with glycaemic deterioration and increased insulin
      secretion independently of changes in other risk factors, suggesting that low
      grade inflammation may contribute to the development of hyperglycaemia and a
      compensatory increase in insulin secretion.

PMID- 30114728
TI  - Bare and nonionic surfactant-functionalized praseodymium oxide nanoparticles:
      Toxicological studies.
AB  - The applications of praseodymium oxide (Pr6O11) nanomaterials in catalysis,
      oxygen storage materials, and optical devices are the emergent areas that possess
      an urgent requirement for the toxicological evaluation of these nanomaterials to
      determine their impact on the ecology. In the present work, we have employed a
      multiassay approach for the toxicological profiling of bare and nonionic surface
      modulated Pr6O11 nanoparticles (NPs). The contemporary analysis in this work has
      presented a great prospect to develop efficient indicators and inspect the toxic
      nature of bare and functionalized Pr6O11 NPs. The effect of Pr6O11 NPs was
      analyzed on germination parameters by the wheat seed germination assay and on
      algal growth by the paper disc approach. The influence of Pr6O11 NPs on the
      percentage viability of four different types of bacteria, namely, Staphylococcus
      aureus, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi, was
      investigated. The substantial effect of different concentrations of Pr6O11 NPs on
      Allium cepa was investigated at the genomic level by using the chromosomal
      aberration assay. The functionalized NPs exhibited 41.05%-400% higher
      biocompatibility by the wheat seed germination assay and 27.1%-47.3% by the A.
      cepa chromosomal aberration assay than the bare NPs. In algal growth assay and
      antibacterial activity testing, biocompatibility of the developed functionalized
      NPs enhanced by 23.1%-37.1% and 10%-70.6%, respectively. The current work
      evaluated the toxicity of the NPs and measured the competence of the obtained
      data to characterize possibilities of probable threats, prominence of data
      requirement, and breaches that must be filled to diminish the ambiguities about
      the safe use of Pr6O11 NPs.

PMID- 30114729
TI  - Analysis of gold and silver nanoparticles internalized by zebrafish (Danio rerio)
      using single particle-inductively coupled plasma-mass spectrometry.
AB  - With the increase in the application of nano-consumer products containing
      engineered nanoparticles (NPs), the unintended environmental exposure to NPs has
      been inevitable. Because of the bioaccumulation of NPs, concern about their
      potential cytotoxicity to aquatic organisms is also growing. Although measuring
      tools for analyzing particle size and/or concentration of NPs in intracellular
      uptake of tissues have been well developed, a simultaneous analysis of the two
      characteristics is difficult. The objective of this study was to use single
      particle-inductively coupled plasma-mass spectrometry (sp-ICP-MS) to measure the
      bioaccumulation and particle size changes of NPs exposed to zebrafish (Danio
      rerio) for 7 days. The uptake of NPs in the liver, intestine, and gill tissues
      was confirmed by electron microscopic (EM) analysis. However, the primary
      particle size of NPs in tissues could not be determined by the EM analysis.
      Therefore, sp-ICP-MS coupled with alkaline digestion was used for the easy
      extraction and immediate analysis of NPs from tissues. Zebrafish were exposed to
      four NPs (30 and 80 nm gold/silver NPs; AuNPs/AgNPs). Uptake amounts of AgNPs in
      the liver and intestine were significantly higher than those of AuNPs. Although
      larger NPs were finally accumulated in the liver and intestine tissues, most of
      the smaller NPs were filtered in the gills. The sp-ICP-MS method coupled with
      alkaline digestion enabled the accurate analysis of size, size distribution, and
      mass concentration of NPs in an aquatic organism.

PMID- 30114730
TI  - Catalytic wet air oxidation of Reactive Black 5 in the presence of LaNiO3
      perovskite catalyst as a green process for azo dye removal.
AB  - The removal of textile azo dye, Reactive Black from the aqueous solutions by
      catalytic wet air oxidation in the presence of LaNiO3 perovskite catalyst has
      been investigated. The most suitable reaction conditions were determined by
      testing various the catalyst loadings, reaction temperature and pressure values,
      and the initial pH of the Reactive Black 5 solutions. The most suitable reaction
      conditions with 0.61 L/min of air flow rate were found to be 1 g/L of LaNiO3
      loading, 50  degrees C of reaction temperature, 1 atm of reaction pressure, and,
      pH = 3 for the oxidation of 100 mg/L Reactive Black solutions. Under these
      conditions the degradation and the decolorization efficiencies were evaluated as
      65.4% and 89.6%, respectively. The phytotoxicity analyzes were carried out by
      using Lepidium sativum. According to the toxicity tests a remarkable decrease in
      the growth inhibition was achieved by the catalytic wet air oxidation in the
      presence of LaNiO3 catalyst. The growth inhibition in the untreated and treated
      dye solutions were calculated as 49.3% and 23.7%, respectively.

PMID- 30114731
TI  - Assessment of cytotoxicity of choline chloride-based natural deep eutectic
      solvents against human HEK-293 cells: A QSAR analysis.
AB  - Deep eutectic solvents (DESs) are a new generation of solvents. To consider them
      as green solvents, investigation of their toxicity is essential. In this work,
      the cytotoxicity of a number of natural deep eutectic solvents (NADESs) against
      HEK-293 human embryonic kidney cells was evaluated by MTT assay. The NADESs were
      prepared with choline chloride (ChCl) as hydrogen-bond acceptor (HBA) and
      different sugar alcohols as hydrogen-bond donor (HBD) constituents. They showed
      IC50 values in the range of 3.52-75.46 mM. These results were used to evaluate
      the effect of structural parameters on the cytotoxicity of the studied NADESs by
      using quantitative structure activity relationship (QSAR) analysis. A three
      parameter linear model was obtained between - log(IC50) as a dependent variable
      and structural descriptors as independent variables. Rotatable bond number (RBN),
      mean atomic van der Waals volume (Mv) and the interaction of second power carbon
      numbers with the molar ratio of HBA to HBD in each NADES (C2 Ratio), were three
      major parameters. The statistical model covered about 76.4% and 69.8% variance of
      data in training and leave-one-out cross-validation, respectively. This work, as
      the first study on the QSAR analysis of DESs, can provide a good perspective for
      designing greener novel DESs.

PMID- 30114732
TI  - Improving leachate quality and optimizing CH4 and N2O emissions from a pre
      aerated semi-aerobic bioreactor landfill using different pre-aeration strategies.
AB  - Landfill aeration efficiently accelerates municipal solid waste (MSW)
      stabilization. This method also impacts methane (CH4) and nitrous oxide (N2O)
      emissions during aeration. In this study, the effects of three pre-aeration
      strategies on leachate quality variations and CH4 and N2O emissions from three
      lab-scale pre-aerated semi-aerobic bioreactor landfills, which were filled with
      MSW, were investigated: low frequency and high frequency intermittent aeration
      (LIA and HIA) and continuous micro-aeration (CMA). Experimental results showed
      that these three strategies effectively reduced organic and N-based pollutants
      concentration in leachate. Compared with intermittent aeration (IA), CMA
      increased cumulative CH4 emissions (9234.3 mg) and resulted in a longer emission
      period (95 days). HIA generated the least cumulative CH4 emissions (4297.6 mg)
      and shortest emission period (65 days) due to organic matter loss during
      aeration. N2O emissions were present at low levels in early stages for each
      bioreactor, and then, increased by 1-3 orders of magnitude in the later stages
      due to low influent carbon-nitrogen ratio. HIA resulted in maximum cumulative N2O
      emissions (2884.6 mg) and experienced a longer emission period (179 days)
      compared to CMA (2281.6 mg; 151 days). LIA had the longest N2O emission period
      (209 days), but had the lowest cumulative N2O emissions (1486.3 mg). CH4 and N2O
      emissions mainly occurred in the early and later stages of landfill
      stabilization, respectively. Therefore, the study proposes an optimized pre
      aeration strategy for practical landfill aeration management: early CMA may
      promote rapid organic matter removal and effective CH4 recovery; and late LIA may
      reduce N2O emissions.

PMID- 30114733
TI  - Heavy metal concentrations and chemical fractions in sediment from Swan Lagoon,
      China: Their relation to the physiochemical properties of sediment.
AB  - This study was performed to determine the distribution and chemical fractions of
      five heavy metals (Cd, Cr, Cu, Pb, and Zn) in sediment from three sampling areas
      in Swan Lagoon, and their relation to the physiochemical properties of sediment
      were explored. The results revealed that Cd in sediment from the sand part (SP),
      muddy sand part (MSP) and sand muddy part (SMP) were potentially highly
      susceptible and bioavailable since the exchangeable fractions were 21.0%, 27.4%,
      and 32.1%, respectively, of the total concentrations. A portion of Pb and Zn were
      observed as reducible fractions owing to their affinity to Fe-Mn; they were able
      to complex with Fe-Mn oxides and oxyhydroxides in the sediment. A large amount of
      Cu in the oxidizable fraction may be due to the fact that Cu can easily form
      stable complexes with organic matter. Cr was overwhelmingly found in the residual
      fraction, suggesting that Cr was strongly bound in mineral lattices. Enrichment
      factors (EF) indicated that Cd in three sampling areas suffered severe
      enrichment, whereas other metals were present in only minor amounts. In addition,
      Cd may pose a medium to high risk in the MSP and SMP based on risk assessment
      codes. According to the mean probable effects level quotient, the samples from
      the MSP and SMP had a 21% probability of toxicity. The multivariate statistical
      analysis suggested that sediment texture (d0.5, sand and silt), Fe-Mn, and the
      total organic carbon (TOC) influenced the distribution of the studied metals and
      their chemical fractions.

PMID- 30114734
TI  - Changes in thyroid status of Menidia beryllina exposed to the antifouling booster
      irgarol: Impacts of temperature and salinity.
AB  - The triazine-based herbicide irgarol is widely used in antifouling systems as an
      algicide and has been detected recently in multiple coastal environments. Studies
      evaluating sub-lethal responses of fish following exposure to irgarol are
      limited. Moreover, impacts of climate change on fish endocrinology may also
      contribute to the sublethal toxicity of irgarol. We assessed the effects of
      irgarol on thyroid endpoints in juveniles of Menidia beryllina under two
      different treatments of salinity (10 and 20 0/00) and two temperatures (10 and 20
      degrees C). Condition factor coefficients (K) of animals were significantly
      affected by 0.1 to 10 MUg/L of irgarol at the higher temperature. Levels of T3
      were changed in whole body homogenates from both temperatures at 100/00 following
      exposure to 1 to 10 MUg/L. T4 levels were altered only at 10 degrees C when
      animals were treated with 1 to 10 MUg/L (10 0/00), and in 0.1 and 10 MUg/L (20
      0/00). Increased transcripts of deiodinase enzymes at 10  degrees C may be
      impacted by salinity and alter thyroid hormone homeostasis. Impact on gene
      expression of thyroid (alpha and beta) and growth hormone receptors were also
      determined. Our results highlight the relevance of environmental variable that
      may impact the ecological risk of irgarol in estuarine systems.

PMID- 30114735
TI  - Kinetics of arsenic absorption by the species Eichhornia crassipes and Lemna
      valdiviana under optimized conditions.
AB  - This work aimed to study the kinetics of arsenic absorption by Eichhornia
      crassipes and Lemna valdiviana under pre-established conditions of pH phosphate
      and nitrate in the nutrient solution. Additional aims were to evaluate the
      conversion kinetics between As(III) and As(V), and the effect of arsenic
      concentrations on development of the species. The plants were cultivated in
      nutrient solutions containing different arsenic concentrations: 0, 0.56, 0.89 and
      1.38 mg L-1 for the water-hyacinth, and 0, 0.13, 0.48, 0.99 and 1.4 mg L-1 for
      Lemna. Monitoring of arsenic removal by the plants was performed by sampling at
      intervals of 0, 4, 8, 16, 24, 48, 96, 144, 192 and 240 h for the water hyacinth,
      and 0, 4, 8, 16, 24, 48, 96, 144 and 168 h for Lemna. The samples were submitted
      to analysis of total arsenic, As(III), As(V) and phosphorus. The first-order
      kinetics was fit to the arsenic removal kinetics by the plants, and it was
      observed that the decay coefficient (k) decreased with the increase of its
      initial concentration in the nutrient solution. For the, absorption was observed
      after 96 h of culture, the time coinciding with the greatest As(V)
      concentrations. For Lemna, the metal was only absorbed by the plant after decay
      of the phosphate levels of the medium, which occurred at 48 h. Concentrations
      above 1 mg L-1 implied deleterious effects in both plant species and in the
      phytoremediation process, and the bioaccumulation factor decreased for
      concentration above this for both E. crassipes and L. valdiviana.

PMID- 30114736
TI  - Effects of bisphenol A in soil on growth, photosynthesis activity, and genistein
      levels in crop plants (Vigna radiata).
AB  - The compound bisphenol A (BPA), an endocrine-disrupting compound that can act as
      an estrogen, is widely used in the industrial manufacture of plastic products and
      epoxy resins. Because of the widespread use of the compound and its use in soil
      amendments, there is concern regarding its effects on crop plants, although
      comparatively little information is available on the ecotoxicity and potential
      risk of bisphenol. Here, we investigated the toxicity of BPA on mung bean (Vigna
      radiata) by evaluating growth, photosynthesis parameters, and phytoestrogen
      changes. Adverse effects on shoot growth were observed at a dose of 750 mg BPA/kg
      dry soil after acute (14 days) and chronic (21 days) exposure, and inhibition of
      root development was confirmed at a dose of 1000 mg BPA/kg dry soil. Chlorophyll
      content and stomatal size decreased at doses of 250 and 500 mg BPA/kg dry soil,
      respectively, and leaf spots due to leaf necrosis were observed in the groups
      that received 250 mg BPA/kg dry soil. Photosynthetic activity appeared to
      decrease in the groups that received the highest exposure, although it was not
      statistically significant. Meanwhile, exposure to bisphenol A increased the level
      of the phytoestrogen genistein. We propose that changes in genistein levels due
      to endocrine-disrupting compounds can be considered as a specific toxicity
      endpoint for endocrine-disrupting chemicals; further studies should explore this
      effect. This study confirmed the phytotoxicity of BPA at various endpoints and
      the results provide a basis for future ecological risk assessment for BPA.

PMID- 30114737
TI  - Modelling PAH partitioning during sludge disintegration: The key role of
      dissolved and colloidal matter.
AB  - The partitioning between solids and the aqueous phase largely controls the fate
      of PAH compounds in biological treatment. The prediction of PAH sorption
      behaviour into activated sludge was investigated here. The suitability of a three
      compartment model to describe partitioning in such a complex matrix was first
      evaluated by adding increasing quantities of dissolved and colloidal matter (DCM)
      (from 0 to 34.9% of the total matter). In a range of DCM concentrations varying
      from 0 to 1.4 g L-1, the PAH aqueous fraction, including both freely dissolved
      and sorbed to DCM molecules, increased from 9.9% to 33% for naphthalene (the most
      soluble PAH) and from 0.29% to 13.3% for indeno(1,2,3,c,d)pyrene (the least
      soluble PAH tested). The sorption of PAHs on dissolved and colloidal matter (DCM)
      was assessed by determining two partitioning constants (KPART and KDCM) for the
      16 PAHs listed by the US EPA. New experiments were carried out for model
      validation and show that the model properly predicts the PAH partitioning
      following sludge disintegration by sonication.

PMID- 30114738
TI  - Salinity influences the interactive effects of cadmium and zinc on ethylene and
      polyamine synthesis in the halophyte plant species Kosteletzkya pentacarpos.
AB  - Salt marshes are major sinks for heavy metals where plants are often exposed to
      polymetallic contamination and high salinity. Seedlings from the wetland
      halophyte plant species Kosteletzkya pentacarpos were exposed during three weeks
      to nutrient solution containing 10 MUM CdCl2, 100 MUM ZnCl2 or a combination of
      the two metals (Cd + Zn) in the presence or absence of 50 mM NaCl. Synthesis of
      the senescing hormone ethylene was quantified together with the concentration of
      protecting polyamines (spermidine and spermine) and their precursor putrescine
      and analyzed in relation to senescence markers (soluble protein, malondialdehyde,
      chlorophyll content and assessment of cell membrane stability). Salinity reduced
      the deleterious impact of heavy metals on plant growth and decreased accumulation
      of the pollutants in the plants. Heavy metals increased ethylene synthesis but
      NaCl decreased it in plants exposed to Cd or to the combined treatment (Cd + Zn)
      but not in plants exposed to Zn alone. Putrescine increased while spermine and
      spermidine decreased in Cd-treated plants. Zinc had only a marginal impact on
      polyamine concentration. The highest putrescine and spermine concentrations were
      observed in plants exposed to the combined treatment. The inhibitor of ethylene
      synthesis (AVG; aminovynilglycine) partially restored plant growth, reduced
      putrescine content and increased spermidine and spermine concentration, leading
      to an attenuation of senescence, mainly in Cd-treated plants. Combined treatment
      induced a specific physiological status in K. pentacarpos which could not be
      fully explained by an additive effect of Cd and Zn. Results are discussed in
      relation to specificities of heavy metals impacts on plant response.

PMID- 30114739
TI  - Degradation of sulfonamide antibiotics and their intermediates toxicity in an
      aeration-assisted non-thermal plasma while treating strong wastewater.
AB  - Aeration-assisted non-thermal plasma (NTP) process is known as promising due to
      simultaneous generation of oxygen- and nitrogen-based reactive chemicals for non
      biodegradable pollutants removal in a wastewater. Despite its effective oxidizing
      capability, the decomposition mechanism of antibiotics is not yet clarified well.
      This study verifies the NTP's removal potential of non-biodegradable sulfonamide
      antibiotics in the treatment of strong wastewater. The instantaneous production
      of hydrogen peroxide (H2O2) was quantified to prove synergistic advanced
      oxidation, and degradation kinetic coefficients of N, N-Dimethyl-4-nitrosoaniline
      (RNO) reveals rapid oxidation rate of NTP. Also, the results of an acute-toxicity
      test using Daphnia magna demonstrate how the toxicity of antibiotics
      intermediates responds to the NTP. Results indicate that the NTP has better
      potential than conventional oxidation processes in terms of OH-radical generation
      due to the interplay of reactive species. This study provides useful information
      that aeration-assisted NTP application to wastewater treatment can be a viable
      option to enhance treatment efficiency via plasma-related reactive species and
      that how environmental ecotoxicity responds to the by-products of sulfonamide
      antibiotics.

PMID- 30114740
TI  - Structural and functional responses of coastal marine phytoplankton communities
      to PAH mixtures.
AB  - The toxicity of polycyclic aromatic hydrocarbons (PAHs) mixtures was evaluated on
      natural phytoplankton communities sampled from lagoons of Bizerte (South-western
      Mediterranean Sea) and Thau (North-western Mediterranean Sea). PAHs induced short
      term dose and ecosystem-dependant decreases in photosynthetic potential.
      Chlorophyll a was negatively affected by increasing PAHs concentrations, together
      with dramatic changes in phytoplankton community composition. Size classes were
      strongly affected in the Bizerte compare to the Thau lagoon, with a decrease in
      nano- and microphytoplankton densities compare to picophytoplankton. In both
      locations, the diatom Entomoneis paludosa appeared favoured under PAH exposure as
      evidenced by increase in cell density, whereas autotrophic flagellates and
      dinophytes were strongly reduced. Smaller cells were more tolerant to exposure to
      highest PAHs concentrations, with persistent picophytoplankton carbon biomass at
      the end of the incubations. Apparent recovery of photosynthetic potential,
      accompanied with a regrowth of chlorophyll a under the lowest PAH doses,
      coincided with a significantly altered community composition in both lagoons.
      Furthermore, sensitivity to PAHs was not related to the phytoplankton cell size,
      and toxicity-induced modification of top-down control by grazers during the
      experiment cannot be excluded.

PMID- 30114741
TI  - Vetiver grass (Chrysopogon zizanioides) is capable of removing insensitive high
      explosives from munition industry wastewater.
AB  - Synthetic organic explosive compounds in the wastewater stream of industrial
      munition facilities are subject to regulatory permits and require pretreatment
      prior to discharge. Munition industries are currently focused on developing
      insensitive high explosives (IHEs) such as dinitroanisole (DNAN), nitroguanidine
      (NQ), and 1,2,4-triazol-3-one (NTO), to replace conventional munitions such as
      trinitrotoluene (TNT) and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). IHEs are
      typically more soluble than conventional explosives, and their production
      generates waste streams with high nitrate (N) concentrations. Several chemical
      remediation studies have attempted to degrade the explosive compounds within
      waste streams with limited success. Phytoremediation is a relatively new
      application for the remediation of munition industry wastewater, which is both
      environmentally and economically sustainable. Vetiver grass (Chrysopogon
      zizanioides), with its massive and dense root system and ability to grow in harsh
      environments, has been observed to remove many chemicals from soil and water,
      including nutrients and TNT. The objective of this study was to evaluate the
      phytoremediation potential of vetiver in removing explosive compounds and N from
      wastewater effluents generated in an industrial munition facility. Results show
      that the removal efficiency of vetiver was a factor of the initial concentration.
      Successive batches of vetiver removed DNAN, NQ, and RDX by 96, 79 and 100%,
      respectively. More than 95% of N was removed by four successive batches of
      vetiver grass. A major portion of NQ and RDX was translocated from root to shoot.
      LC-MS analysis showed the presence of transformation products of RDX, HMX
      (1,3,5,7-Tetranitro-1,3,5,7-tetrazocane) and DNAN in vetiver root and shoot.

PMID- 30114742
TI  - Application of field-portable-XRF for the determination of trace elements in
      deciduous leaves from a mine-impacted region.
AB  - Deciduous leaves (n = 87) from beech (Fagus sylvatica), birch (Betula spp.) and
      oak (Quercus spp.) trees have been collected from three metal mine-impacted sites
      in southwest England and tested for concentrations of trace elements (As, Cu, Pb
      and Zn) using a field-portable-x-ray fluorescence (FP-XRF) spectrometer
      configured in a low density mode and housed in a stand. When intact leaves were
      analysed directly, mean detection limits ranged from about 10 (As) to 70 MUg g-1
      (Cu) on a fresh weight basis; after freeze-drying, respective limits increased to
      about 20 and 120 MUg g-1 on a dry weight basis. Within these constraints, As and
      Zn were detected in samples from all genera, with concentration differences
      between fresh and dry states attributed to the mass of water present and its
      propensity to attenuate x-rays. A comparison with As and Zn concentrations in
      local soils and determined by XRF in a higher density mode revealed different
      accumulation and exclusion characteristics among the three genera of tree. In
      contrast, and despite soil concentrations that were similar to those of Zn, Cu
      was detected in only two dried leaves and Pb evaded detection throughout. Pooled
      results from the study showed good agreement with independent results derived
      from ICP following acid digestion, with a slope defining the overall relationship
      that was close to unit value. Accordingly, the XRF approach is able to provide a
      rapid assessment of the levels of certain trace elements in leaves from
      contaminated sites, with the configuration deployed on site having potential to
      deliver immediate results.

PMID- 30114743
TI  - Exploring the relationship between molecular structure of dyes and light sources
      for photodegradation and electricity generation in photocatalytic fuel cell.
AB  - Reactive green 19, acid orange 7 and methylene blue are employed as the organic
      pollutants in this work. A photocatalytic fuel cell is constructed based on the
      idea of immobilizing zinc oxide onto zinc photoanode and platinum loaded carbon
      cathode, both evaluated under sunlight and ultraviolet irradiation, respectively.
      Influence of light and dye structures on the performance of photocatalytic fuel
      cell are examined. With reactive green 19, 93% and 86% of color removal are
      achieved after 8 h of photocatalytic fuel cell treatment under sunlight and
      ultraviolet irradiation, respectively. The decolorization rate of diazo reactive
      green 19 is higher than acid orange 7 (monoazo dye) when both dyes are treated by
      photocatalytic fuel cell under sunlight and ultraviolet irradiation, as the
      electron releasing groups (-NH-triazine) allow reactive green 19 easier to be
      oxidized. Comparatively, acid orange 7 is less favorable to be oxidized. The
      degradation of methylene blue is enhanced under sunlight irradiation due to the
      occurrence of self-sensitized photodegradation. When methylene blue is employed
      in the photocatalytic fuel cell under sunlight irradiation, the short circuit
      current (0.0129 mA cm-2) and maximum power density (0.0032 mW cm-2) of
      photocatalytic fuel cell greatly improved.

PMID- 30114745
TI  - The characteristics of organic matter influence its interfacial interactions with
      MnO2 and catalytic oxidation processes.
AB  - The influence of dissolved organic matter (DOM) properties on its interfacial
      interactions with MnO2 and on catalytic oxidation processes was studied by Time
      Resolved Dynamic Light Scattering (TR-DLS) and Atomic Force Microscopy (AFM)
      under varied solution conditions. Four DOM fractions of different characteristics
      (e.g., SUVA, hydrophobic character, structural properties) were selected. Bared
      MnO2 nanoparticles readily aggregated in NaCl and CaCl2 solutions. Classic DLVO
      Theory successfully described critical coagulation concentrations and aggregation
      behaviors. In NaCl solution, DOM adsorbed on MnO2 nanoparticles and provided
      electrosteric stabilization. The two DOM fractions of higher hydrophobic (HPO)
      character were more efficient in decreasing the aggregation rates. Enhanced MnO2
      aggregation was observed at high Ca2+ concentrations due to charge screening and
      cation bridging between carboxyl groups in DOM structures. The addition of
      oxidant (H2O2) induced a high aggregation of bared-MnO2 nanoparticles, possibly
      due to the release of Mn2+ (i.e., complexation mechanisms) and generation of
      reactive species (O2-, HO2-, and H). Contrasted with their hydrophilic (HPI)
      counterparts, HPO isolates adsorbed on MnO2 significantly decreased the catalytic
      oxidation processes between H2O2/MnO2; suggesting a more efficient and stronger
      DOM coating. Interfacial forces measured by AFM, showed weaker interactions
      between HPI isolates and MnO2; suggesting unfavorable polar interactions.
      Conversely, the high adhesion forces between MnO2/HPO isolate would indicate
      stronger bonds and hydrophobic interactions. This study provided a nanoscale
      understanding of the impact of DOM characteristics on: a) performance of the MnO2
      coated ceramic membranes in water treatment, and b) biogeochemical cycle of Mn
      oxides in the environmental.

PMID- 30114746
TI  - Zinc alleviates copper toxicity to symbiotic nitrogen fixation in agricultural
      soil affected by copper mining in central Chile.
AB  - According to the Terrestrial Biotic Ligand Model, other cations might compete
      with Cu+2 for biotic ligand sites and provide a protective effect. In particular,
      evidence suggests Zn may alleviative Cu toxicity. No study, to the best of our
      knowledge, has focused explicitly on the alleviating effect Zn might have on Cu
      toxicity to soil microorganisms in field-contaminated soils. The aim of this
      study was to investigate the alleviating effect Zn might have on Cu toxicity to
      symbiotic nitrogen fixation in agricultural soils affected by copper mining in
      central Chile. The bioassay estimated the symbiotic nitrogen fixation capacity of
      a population of rhizobia in a specified soil, using the soil as inocula for
      Phaseolus vulgaris L. grown in a soil-less system (pots with perlite) irrigated
      with a sterile nitrogen-free nutrient solution. Among all soil physicochemical
      characteristics, the Cu/Zn ratio best explained changes in symbiotic nitrogen
      fixation. The effective concentration 50% (EC50) of Cu/Zn ratio for symbiotic
      nitrogen was equal to 1.2, with 95% confidence interval of 1.0-1.3. Symbiotic
      nitrogen fixation decreased with increased Cu/Zn ratio, thus suggesting that Zn
      alleviates Cu toxicity to nitrogen fixing microorganisms.

PMID- 30114744
TI  - Air pollution associated with non-suicidal self-injury in Chinese adolescent
      students: A cross-sectional study.
AB  - BACKGROUND: Non-suicidal self-injury (NSSI) is a frequent phenomenon in
      adolescents and is closely related to eventual suicide. Although the effect of
      air pollution on various diseases has been extensively investigated, no studies
      examined its effect on NSSI in young students. OBJECTIVES: We investigated the
      effect of air pollution on NSSI in Chinese students. METHODS: We investigated the
      incidence of NSSI in the past 12 months in 54 923 Chinese students with an
      anonymous questionnaire. We assessed the air pollution exposure of each student
      by the air quality matched with their schools, which were calculated by the
      inverse distance weighting method from the environmental monitoring data. We
      discussed the association between ambient air pollutants and the incidence of
      NSSI using generalized additive mixed models. RESULTS: A 10 MUg/m3 increase in
      the annual moving average concentration of particulate matter with diameters less
      than 2.5 MUm (PM2.5) and ozone (O3) was associated with a 13.9 percent and a 10.5
      percent increase in the odds ratio (OR) of NSSI, respectively. In addition, a 0.1
      mg/m3 increase in the annual moving average concentration of carbon monoxide (CO)
      was associated with a 4.8 percent increase in the OR of NSSI. NO2 and SO2 were
      not related to NSSI. CO and O3 show non-linear effects on NSSI. Male students in
      high school are the most s to the effects of PM2.5 on NSSI. CONCLUSIONS: Our
      study suggests that increases in PM2.5, O3 and CO may increase the incidence of
      NSSI among adolescent students.

PMID- 30114747
TI  - The silk gland damage and the transcriptional response to detoxifying enzymes
      related genes of Bombyx mori under phoxim exposure.
AB  - Silk gland is a major organ of Bombyx mori for the synthesis and secretion of
      silk protein. Phoxim exposure can be toxic to B. mori and causes a decrease of
      fibroin synthesis, finally affecting the silk production in industry. To study
      the mechanism of metabolism and detoxification of silk gland under phoxim
      exposure, we measured the residual quantity of phoxim in silk gland and hemolymph
      after phoxim exposure, and the detoxifying enzymes-related genes and enzyme
      activity were also investigated. Results indicated that the residual amount of
      phoxim existed up to 24 h in silk gland compared with that in hemolymph,
      suggesting that phoxim can accumulate in the silk glands within a certain time
      course. The transcriptional levels of PI3K/Akt genes, including Akt, Tor1, p70s6k
      and 4e-bp, were up-regulated by 6.919, 1.358, 10.766 and 7.708-fold,
      respectively. The expression of two downstream genes (CncC and Keap1) was up
      regulated by 1.939 and 3.373-fold, respectively. In addition, the transcriptional
      levels of detoxification-related genes including CYP6AB, CYP306A, CarE2, GST1 and
      GSTd1 were up-regulated by 1.731, 1.221, 1.366, 1.376 and 6.591-fold,
      respectively. The enzymatic activity of CYP450, CarE and GST were increased over
      time. These results provided possible insights into the injury of silk gland and
      the transcriptional response to detoxifying enzymes-related genes in silkworm
      after phoxim exposure.

PMID- 30114749
TI  - Di (2-ethyl hexyl) phthalate (DEHP)-induced kidney injury in quail (Coturnix
      japonica) via inhibiting HSF1/HSF3-dependent heat shock response.
AB  - Di (2-ethyl hexyl) phthalate (DEHP) as a plasticizer can leach away from the
      plastic and hence entrances into the animal food chain which caused serious
      hazard in organs of animals, but there are few studies on DEHP kidney toxicity.
      The heat-shock response (HSR) consisting of the HSPs and HSFs plays an important
      role in various toxicity stress conditions. To investigate the influence on
      kidney toxicity and the modulation of HSR during DEHP exposure, female quail were
      fed the diet with 0, 250, 500 and 750 mg/kg DEHP by gavage administration for 45
      days. The shrinkages of glomeruli and dilation of kidney tubule epithelia cells
      were observed in the kidney of DEHP-exposed quail. DEHP treatment could
      significantly decrease the expressions of HSP25, HSP27, HSP47, HSP60, while the
      expressions of HSP10, HSP40, HSP70, HSP90, HSP110 were upregulated in the kidney.
      In addition, the expression levels of HSF1 and HSF3 were significantly increased
      under DEHP. This is the first study to demonstrate quail exposure to DEHP is in
      fact detrimental to bird kidney. Besides, DEHP could attack HSR by affecting the
      synthesis of HSFs to mediate the transcription of the HSPs resulting in kidney
      damage.

PMID- 30114748
TI  - AlCl3 inhibits LPS-induced NLRP3 inflammasome activation and IL-1beta production
      through suppressing NF-kappaB signaling pathway in murine peritoneal macrophages.
AB  - Aluminum (Al), a common environmental pollutant, has been reported to inhibit the
      immune functions of macrophage. However, the mechanisms involved remain unclear.
      In this study, murine peritoneal macrophages were exposed to 0, 0.27, 0.54, and
      1.08 mg/mL of aluminium chloride (AlCl3) for 24 h, and then treated with 1 MUg/mL
      lipopolysaccharide (LPS) for another 6 h. No addition of both AlCl3 and LPS
      serviced as control group. We observed that AlCl3 has cytotoxicity in murine
      peritoneal macrophages, showing a decrease in cell viability and an increase in
      lactate dehydrogenase release. Besides, AlCl3 exposure restrained the LPS-induced
      NLR pyrin domain containing 3 (NLRP3) inflammasome activation presented as NLRP3
      expressions reduction, caspase-1 cleavage inhibition and interleukin 1 beta (IL
      1beta) maturation lessened. Meanwhile, AlCl3 exposure decreased LPS-induced
      IKKbeta activity, IkappaBalpha phosphorylation, the phosphorylation and mRNA
      expression of NF-kappaB p65, as well the genes expression and concentration in
      medium supernatant of tumor necrosis factor alpha (TNF-alpha) and interleukin 6
      (IL-6). The results suggested that AlCl3 inhibited the activation of NF-kappaB
      signaling pathway induced by LPS, which maybe one of the upstream signals
      involved in the inhibition of NLRP3 inflammasome activation by AlCl3. This
      research can provide theoretical basis for understanding the immune toxicity of
      Al, and deepening the cognition of Al exposure hazards to immune response.

PMID- 30114750
TI  - Phytotoxic activity of diclofenac: Evaluation using a model green alga
      Chlamydomonas reinhardtii with atrazine as a reference substance.
AB  - Human activities have caused increasing inputs of pharmaceuticals to the
      environment and diclofenac (DF) is one of the most commonly detected in
      freshwater systems. The aim of this study was to determine the impact of DF on a
      freshwater green alga as a non-target organism. For DF toxicity evaluation, its
      effects on a model organism Chlamydomonas reinhardtii were compared with effects
      caused by the herbicide atrazine (AT). EC50 values were about 135 mg/L for DF and
      78 mg/L for AT, respectively. Both toxicants enhanced H2O2 production by the
      cells (144% and 178% of control for AT and DF, respectively) and stimulated
      catalase activity (~200% of control). Activity of ascorbate peroxidase was
      elevated in AT-cells but not in DF-treated cells. DF did not influence dark
      respiration of the cells, whereas AT inhibited this process by about 50% compared
      to the control. Both toxicants caused photosynthesis inhibition. Analysis of
      parameters of chlorophyll a fluorescence in vivo showed diminishment of a
      performance index (PI) in both DF- and AT-treated cells (~50% of control), but
      the reasons for the changes detected were different. AT diminished the efficiency
      of electron transport between PS II and PS I without significant inhibition of PS
      II or PS I reaction centers (RCs). In contrast to AT, DF seemed to influence
      directly PS II RCs. The fraction of active PS II RCs was lowered in DF-treated
      cells, but energy flux per active RC increased. Our study indicates that DF
      phytotoxicity results mainly from photosynthesis inhibition due to "silencing" of
      a fraction of PS II RCs.

PMID- 30114752
TI  - Mapping the electric field distribution of tightly focused cylindrical vector
      beams with gold nanorings.
AB  - In this paper gold nanorings (NRs) are applied as particularly well-suited
      sensing elements for mapping the radially symmetric electric fields in the high
      numerical aperture focus of cylindrical vector beams. The optical properties of
      gold nanorings are analyzed by a combination of extinction and single particle
      dark field spectroscopy as well as confocal photoluminescence (PL) imaging. The
      results are compared to numerical calculations. The in-plane components in the
      focus of the cylindrical vector beams are estimated through the PL intensity
      distributions of the NRs. The optimum overlap between the structure and
      excitation is visualized by a narrow centre spot in the far-field PL scan.

PMID- 30114751
TI  - Enhanced degradation of ibuprofen by heterogeneous electro-Fenton at
      circumneutral pH.
AB  - Fenton based reactions are effective for pharmaceutical removals, but traditional
      Fenton processes have drawbacks of pH adjustment and large amount of produced
      iron sludge. To overcome these challenges, a heterogeneous electro-Fenton process
      was proposed for effective contaminant degradation at circumneutral pH without
      iron sludge production. The anti-inflammatory drug ibuprofen (a common
      pharmaceutical in natural waters) was used as a representative contaminant.
      Activated carbon fibers (ACFs) supported ferric citrate (Cit-Fe/ACFs) was
      synthesized and used as the cathode, and RuO2/Ti was used as the anode. H2O2 was
      electro-generated in situ from O2 reduction and the production rate of OH per
      unit area was 6.8 MUM W-1 cm-2 using Cit-Fe/ACFs cathode. A maximal ibuprofen
      degradation of 97% was obtained after 120 min at the current density of 7 mA cm
      2. The electrical energy per order (EEO) varied from 0.24+/-0.03 to 2.65+/-0.04
      kWh log-1 m-3 when the current density ranged from 1 to 7 mA cm-2. The Cit
      Fe/ACFs cathode showed relatively good reusability and ~85% IBP removal was
      achieved after 6 cycles of degradation. Our results showed that the prepared Cit
      Fe/ACFs cathode was promising for the treatment of pharmaceutical contaminants.

PMID- 30114753
TI  - Interferometric analysis of sub-nanosecond laser-induced optical breakdown
      dynamics in the bulk of fused-silica glass.
AB  - Dynamics of laser-induced optical breakdown in the bulk of fused-silica glass
      irradiated by a sub-nanosecond laser pulse at a wavelength of 790 nm with a
      fluence of 522 J/cm2 was studied by the femtosecond time-resolved complex
      interferometry in Nomarski arrangement utilising a Fresnel bi-prism. Evolution of
      the plasma channel and the development of the free electron density were in focus
      of the investigation. The measured ultimate length of the plasma channel was
      equal to 30 MUm and almost doubled the length estimated within the moving
      breakdown model. The history of the transient electron density distribution in
      the plasma was reconstructed from the phase shift maps using the inverse Abel
      transform and it revealed further deviation from this model. The core of the
      plasma channel exhibited at the last stages of the development a considerable
      level of the electron density up to 2.4*1020 cm-3. The signature of the pre
      breakdown phase has been identified as radiation caused by ionization-released
      electrons interacting with ions and has been demonstrated in solids for the first
      time in this way. Origin of the discrepancy between the theoretical prediction of
      the moving breakdown model and the measured values of the channel length is
      discussed as well.

PMID- 30114754
TI  - Prime number decomposition using the Talbot effect.
AB  - We report on prime number decomposition by use of the Talbot effect, a well-known
      phenomenon in classical near field optics whose description is closely related to
      Gauss sums. The latter are a mathematical tool from number theory used to analyze
      the properties of prime numbers as well as to decompose composite numbers into
      their prime factors. We employ the well-established connection between the Talbot
      effect and Gauss sums to implement prime number decompositions with a novel
      approach, making use of the longitudinal intensity profile of the Talbot carpet.
      The new algorithm is experimentally verified and the limits of the approach are
      discussed.

PMID- 30114755
TI  - Estimation of particle size distributions from bulk scattering spectra:
      sensitivity to distribution type and spectral noise.
AB  - A shape dependent method for particle size distribution (PSD) estimation based on
      bulk scattering properties was elaborated. This method estimates the parameters
      of a particle size distribution with predefined shape from the bulk scattering
      spectra. The estimation routine was validated on simulated data of polystyrene in
      water suspensions. To investigate the effect of measurement errors on PSD
      estimates, a sensitivity analysis was performed. The influence of spectral
      resolution and range was rather limited. Good PSD estimations were obtained on
      noise-free spectra, spectra with limited random noise and for estimations on MUs
      or MUs' in case of a multiplicative baseline. However, the PSD estimation
      deteriorated if an incorrect value for the refractive index of the particle
      relative to the medium was used as input parameter. Deviations caused by an
      incorrect distribution type were smaller for more narrow PSDs than for broader
      ones. Overall, this study showed the potential to estimate PSDs from bulk
      scattering spectra and indicated the factors affecting the accuracy.

PMID- 30114756
TI  - Real-time superchannel transmission over 10,500 km submarine link at 4.66 b/s/Hz
      spectral efficiency.
AB  - We show real-time measurement of error-free superchannel transmission over more
      than 10,500 km of large-area fiber at a spectral efficiency of 4.66 b/s/Hz,
      utilizing subcarrier based signal processing optimized at 5.4 GBd.

PMID- 30114757
TI  - Transmitter skew tolerance and spectral efficiency tradeoff in high baud-rate QAM
      optical communication systems.
AB  - Residual IQ skew in a coherent transmitter severely degrades the performance of
      long-haul coherent optical communication systems. The impairment is particularly
      detrimental for a high baud-rate system using quadrature amplitude modulation
      (QAM). Furthermore, Nyquist pulse shaping increases the spectral efficiency for
      WDM systems. However, sharp roll-off of Nyquist pulse shaping further reduces the
      tolerance to residual IQ skew. Thus, certain trade-offs between spectral
      efficiency and roll-off factor should be made to improve the tolerance of
      residual IQ skew. We experimentally studied this trade-off and determined the
      optimal roll-off factor, channel spacing, receiver bandwidth, and equalizer
      length. The results serve as a guideline for high baud-rate coherent WDM systems.

PMID- 30114758
TI  - Random two-step phase shifting interferometry based on Lissajous ellipse fitting
      and least squares technologies.
AB  - To accurately obtain the phase distribution of an optical surface under test, the
      accurate phase extraction algorithm is essential. To overcome the phase shift
      error, a random two-step phase shifting algorithm, which can be used in the
      fluctuating and non-uniform background intensity and modulation amplitude,
      Lissajous ellipse fitting, and least squares iterative phase shifting algorithm
      (LEF&LSI PSA), is proposed; pre-filtering interferograms are not necessary, but
      they can get relatively accurate phase distribution and unknown phase shift
      value. The simulation and experiment verify the correctness and feasibility of
      the LEF & LSI PSA.

PMID- 30114759
TI  - Imaging of objects through a thin scattering layer using a spectrally and
      spatially separated reference.
AB  - Incoherently illuminated or luminescent objects give rise to a low-contrast
      speckle-like pattern when observed through a thin diffusive medium, as such a
      medium effectively convolves their shape with a speckle-like point spread
      function (PSF). This point spread function can be extracted in the presence of a
      reference object of known shape. Here it is shown that reference objects that are
      both spatially and spectrally separated from the object of interest can be used
      to obtain an approximation of the point spread function. The crucial observation,
      corroborated by analytical calculations, is that the spectrally shifted point
      spread function is strongly correlated to a spatially scaled one. With the
      approximate point spread function thus obtained, the speckle-like pattern is
      deconvolved to produce a clear and sharp image of the object on a speckle-like
      background of low intensity.

PMID- 30114760
TI  - Generation of Raman dissipative solitons near 1.3 microns in a phosphosilicate
      fiber cavity.
AB  - An external-cavity generation of powerful ultrashort pulses in an all-fiber
      scheme by using a new type of phosphosilicate polarization maintaining fiber is
      investigated. The phosphorus-related Stokes shifted Raman pulse near 1.3 microns
      is observed. Optimization of Stokes output spectrum depending on pump pulse
      duration (chirp), energy and output coupling ratio of the cavity is performed. As
      result, the output energy of highly-chirped pulses compressible to 570 fs reaches
      1.6 nJ.

PMID- 30114761
TI  - Interferometric autocorrelation of ultrafast optical pulses in silicon sub
      micrometer p-i-n waveguides.
AB  - We investigated the high-sensitivity interferometric autocorrelation of ultrafast
      optical pulses utilizing two-photon absorption in sub-micrometer silicon p-i-n
      waveguides. The autocorrelation sensitivities were evaluated to be about 0.5 and
      4.5 * 10-8 W2 for 1- and 0.5-mm devices, respectively. Such sensitivities are
      about 100 times higher than the traditional two-photon conductivity
      photodetectors in commercial autocorrelators; thus favor weak pulse
      characterization. We comprehensively studied the interferometric autocorrelation
      performances by the experiment and FDTD (finite-difference time-domain)
      simulation. The pulse energy dependences of measured autocorrelation
      photocurrents and pulse widths were well explained by the simulation with the
      free carrier absorption and free carrier plasma effect considered. The
      autocorrelation error tends to occur if the pulse energy is high enough to cause
      strong free carrier effects and the threshold pulse energy for error occurrence
      is increased for shorter devices, but accurate autocorrelation measurement was
      achieved for sub-Watts pulses at which the influences of free carrier effects on
      interferometric autocorrelation was negligible. The minimum applicable range of
      pulse widths was estimated from waveguide dispersion analysis to be ~0.09 and
      0.13 ps with a 10% target error for 0.5-mm and 1-mm devices, respectively. The
      interferometric autocorrelation in sub-micrometer silicon p-i-n waveguides is
      promising as a monolithic photonic device for on-chip monitor and diagnostics of
      weak ultrafast pulses.

PMID- 30114762
TI  - Symmetric polarization-insensitive directional couplers fabricated by femtosecond
      laser writing.
AB  - We study analytically the polarization behaviour of directional couplers composed
      of birefringent waveguides, showing that they can induce polarization
      transformations that depend on the specific input-output path considered. On the
      basis of this study, we propose and demonstrate experimentally, by femtosecond
      laser writing, directional couplers that yield a polarization-independent power
      splitting and, at the same time, preserve the polarization state of the
      propagating light. More in detail, we devise two different approaches to realize
      such devices: the first one is based on local birefringence engineering by
      additional refractive index modification tracks, while the second one exploits
      ultra-low birefringence waveguides (b = 1.2 * 10-6), obtained by thermal
      annealing.

PMID- 30114763
TI  - Efficient marching solver for a class of three-dimensional optical waveguides.
AB  - An efficient marching method of the wave propagation computation in the three
      dimensional (3D) rectangular box is developed by solving the scalar Helmholtz
      equation with the weakly range-dependent refractive-index or wavenumber profile.
      The method is based on the application of the one-way formulation accompanied by
      a truncated technique that allows for the reduction of the number of eigenmodes
      and for quickly achieving reliable numerical results. The merits of the high
      accuracy and fast computation with a larger range step are shown to solve the
      equation. This treatment can be also applied to other complicated 3D waveguides.

PMID- 30114764
TI  - All-fiber polarization beam splitting and rotating based on vector-mode-assisted
      coupling.
AB  - We propose and design a new kind of all-fiber polarization beam splitter and
      rotator (PBS and PBR) based on vector-mode-assisted coupling. By embedding a high
      contrast-index ring-core between two cores of the conventional fiber couplers,
      being a three-core coupling structure, the state of polarization (SOP) of fiber
      guided modes can be availably controlled, such as polarization splitting and
      rotating, by transitional coupling through TM01 or TE01 vector mode. Furthermore,
      the SOP of coupled mode can be rotated with arbitrary angle under different three
      core layouts. In particular, by exploiting HE21-assisted coupling case, we can
      realize full-dimensional SOP rotation for arbitrary polarization input. We give
      the numerical simulation for the proposed all-fiber PBS and PBR, and investigate
      the corresponding polarization extinction ratio and polarization rotating purity
      in detail. The calculation results manifest a favorable performance on SOP
      management of fiber-guided modes. This vector-mode-assisted coupling might be
      expected to find potential applications in the polarization-based optical signal
      processing, multiplexing, and sensing system.

PMID- 30114765
TI  - Numerical model built for the simulation of the earth magnetopause by lobster-eye
      type soft X-ray imager onboard SMILE satellite.
AB  - Solar wind magnetosphere ionosphere link explorer (SMILE) scientific satellite is
      dedicated to observe solar wind-magnetosphere coupling. The key payload, soft X
      ray imager (SXI), is designed to map the location, shape, and motion of dayside
      magnetospheric boundaries by Angel-type lobster-eye optical system. Contrast to
      traditional Wolter-type X-ray telescope with very narrow field-of-view, the
      lobster-eye-type optics has a unique capability of providing wide field of view
      for panoramic imaging with moderate spatial resolution in soft X-ray band. Since
      the lobster-eye optics focus X-ray by reflecting of the inner walls of the micro
      channel array shaped in spherical surface, traditional optical design tools can't
      well match to the requirements of simulation for SXI. In this paper, a 3D Angel
      type lobster-eye model is designed for simulation of lobster-eye optics and its
      capability is demonstrated for the applying scenarios including the imaging of
      point light source, surface light source with uniform and non-uniform intensity
      distribution. The simulation results are well consistent with those of
      theoretical estimate.

PMID- 30114766
TI  - Accurate effective atomic number determination with polychromatic grating-based
      phase-contrast computed tomography.
AB  - The demand for quantitative medical imaging is increasing in the ongoing
      digitalization. Conventional computed tomography (CT) is energy-dependent and
      therefore of limited comparability. In contrast, dual-energy CT (DECT) allows for
      the determination of absolute image contrast quantities, namely the electron
      density and the effective atomic number, and is already established in clinical
      radiology and radiation therapy. Grating-based phase-contrast computed tomography
      (GBPC-CT) is an experimental X-ray technique that also allows for the measurement
      of the electron density and the effective atomic number. However, the
      determination of both quantities is challenging when dealing with polychromatic
      GBPC-CT setups. In this paper, we present how to calculate the effective atomic
      numbers with a polychromatic, laboratory GBPC-CT setup operating between 35 and
      50?,kVp. First, we investigated the accuracy of the measurement of the
      attenuation coefficients and electron densities. For this, we performed a
      calibration using the concept of effective energy. With the reliable experimental
      quantitative values, we were able to evaluate the effective atomic numbers of the
      investigated materials using a method previously shown with monochromatic X-ray
      radiation. In detail, we first calculated the ratio of the electron density and
      attenuation coefficient, which were experimentally determined with our
      polychromatic GBPC-CT setup. Second, we compared this ratio with tabulated total
      attenuation cross sections from literature values to determine the effective
      atomic numbers. Thus, we were able to calculate two physical absolute quantities 
      - the electron density and effective atomic number -- that are in general
      independent of the specific experimental conditions like the X-ray beam spectrum
      or the setup design.

PMID- 30114767
TI  - Frequency noise suppression of optical injection-locked quantum cascade lasers.
AB  - This work theoretically investigates the frequency noise (FN) characteristics of
      quantum cascade lasers subject to the optical injection through a set of coupled
      rate equations with Langevin noise sources. It is shown that the low-frequency FN
      is completely suppressed by the optical injection, and the suppression bandwidth
      increases with the increasing injection ratio. The optimal FN peak suppression
      ratio at an injection ratio of 10 dB reaches 2.9 dB. In addition, it is found
      that the optical injection at positive frequency detunings close to the locking
      boundary invokes an additional peak in the FN spectrum, which can be higher than
      the carrier noise-induced one of free-running lasers. This peak amplitude
      strongly depends on the value of the linewidth broadening factor. Unlike
      injection-locked interband lasers, the FN peak does not necessarily exhibit a
      resonance.

PMID- 30114768
TI  - Ultrafast shifted-core coaxial nano-emitter.
AB  - We present an ultrafast nanoscale light source utilizing a shifted-core coaxial
      nano-cavity, with a footprint of merely one-third of its emission wavelength in
      all three dimensions at telecommunication wavelengths. We show that, by shifting
      the metallic core off center of the coaxial structure, the effective mode volume
      of the cavity can be as small as 0.0078 * (lambda0/na)3, resulting in a Purcell
      factor over 390 and a modulation bandwidth exceeding 60GHz. We further show that
      the evolution trend of the cavity Q factor as a function of core-shifting
      distance can be engineered by choosing proper substrate material. Compared to its
      symmetric counterpart, this shifted-core coaxial nano-cavity features not only
      higher Q factor, Purcell factor, and modulation bandwidth but also an improved
      emission directivity that is essential in its coupling with other on-chip
      components. The proposed nano-emitter also features robust single mode operation
      over the entire core-shifting range, resulting in a near-unity spontaneous
      emission factor. Therefore, this device can be a good candidate for low power
      optical interconnect applications.

PMID- 30114769
TI  - Micron-precision measurement using a combined frequency-modulated continuous wave
      ladar autofocusing system at 60 meters standoff distance.
AB  - In this paper, we propose a novel combined frequency-modulated continuous wave
      (FMCW) ladar autofocusing system and a fast compensation method for dispersion
      mismatch, which could allow high-precision ranging to be performed at a long
      distance. By using the dual-beam laser autofocusing system based on a liquid
      lens, this system can quickly complete a measurement with high-precision. The
      experimental results showed that the precision was below 126 MUm in a range up to
      60m, corresponding to a relative precision of 2.1 * 10 -6, compared to a
      reference interferometer.

PMID- 30114770
TI  - Fiber optic method for obtaining the peak reflected pressure of shock waves.
AB  - Most of fiber-optic pressure sensors used in shock wave measurements are based on
      deformations of sensing elements. These approaches result in low dynamic pressure
      ranges for these sensors used in the air. A novel fiber-optic method based on the
      relationship between pressure and the acceleration of a diaphragm is proposed to
      obtain peak reflected pressure of shock waves in the air. The optical sensor is
      designed with a thin circular diaphragm as the sensing element, and the Fabry
      Perot optical interferometry is used to detect the acceleration of the diaphragm.
      Shock tube and explosive-blast experiments prove that the proposed fiber optic
      method is feasible and has the advantages of no calibration, high precision and
      fast response time. The proposed fiber-optic pressure method has potential in
      practical applications for shock wave measurements.

PMID- 30114771
TI  - Si-based Mach-Zehnder wavelength/mode multi/demultiplexer for a WDM/MDM
      transmission system.
AB  - We propose and experimentally demonstrate a low-loss and low-crosstalk Mach
      Zehnder mode/wavelength multi/demultiplexer for WDM/MDM transmission based on a
      Si-photonics platform. A broadband 3-dB mode divider, which is also newly devised
      here, makes it possible to compose a Mach-Zehnder filter for "mode" and
      "wavelength" simultaneously. Transmission characteristics of fabricated 3-dB mode
      dividers are in excellent agreement with theoretical results. Mach-Zehnder
      filters using the 3-dB mode divider with a free spectral range (FSR) of 20 and 1
      nm are also fabricated and the modal crosstalk is less than -24 dB in the 40-nm
      wavelength range for the MZ filter with an FSR of 20 nm. The tuning of the peak
      wavelength position by the TiN heater is also demonstrated.

PMID- 30114772
TI  - Machine-learning techniques for fast and accurate feature localization in
      holograms of colloidal particles.
AB  - Holograms of colloidal particles can be analyzed with the Lorenz-Mie theory of
      light scattering to measure individual particles' three-dimensional positions
      with nanometer precision while simultaneously estimating their sizes and
      refractive indexes. Extracting this wealth of information begins by detecting and
      localizing features of interest within individual holograms. Conventionally
      approached with heuristic algorithms, this image analysis problem can be solved
      faster and more generally with machine-learning techniques. We demonstrate that
      two popular machine-learning algorithms, cascade classifiers and deep
      convolutional neural networks (CNN), can solve the feature-localization problem
      orders of magnitude faster than current state-of-the-art techniques. Our CNN
      implementation localizes holographic features precisely enough to bootstrap more
      detailed analyses based on the Lorenz-Mie theory of light scattering. The wavelet
      based Haar cascade proves to be less precise, but is so computationally efficient
      that it creates new opportunities for applications that emphasize speed and low
      cost. We demonstrate its use as a real-time targeting system for holographic
      optical trapping.

PMID- 30114773
TI  - 2D Monte Carlo simulation of a silicon waveguide-based single-photon avalanche
      diode for visible wavelengths.
AB  - Integrated photonics platforms are crucial to the development and implementation
      of scalable quantum information and networking schemes, but many such devices
      still rely on external bulk photodetectors. We report the design and simulation
      of a waveguide-based single-photon avalanche diode (SPAD) for visible
      wavelengths. The SPAD consists of a p-n junction implemented in a doped silicon
      waveguide, which is end-fire coupled to an input silicon nitride waveguide. We
      developed a 2D Monte Carlo model to simulate the avalanche multiplication process
      of charge carriers following the absorption of an input photon, and calculated
      the photon detection efficiency (PDE) and timing jitter of the SPAD. We
      investigated the SPAD performance at a wavelength of 640 nm and temperature of
      243K for different device dimensions and device doping configurations. For our
      simulated parameters, we obtained a maximum PDE of 0.45 at a reverse bias voltage
      of ~20 V, and full-width-half-max (FWHM) timing jitter values <8 ps.

PMID- 30114774
TI  - Layer thickness dependence of the terahertz emission based on spin current in
      ferromagnetic heterostructures.
AB  - The emission with a bandwidth of 1.5 terahertz based on the spin current in the
      ferromagnetic heterostructure Co/Pt is demonstrated. The spin transient launched
      by the NIR femtosecond laser pulse in the Co/Pt is converted into the in-plane
      charge current due to the inverse spin Hall effect, which gives rise to the
      terahertz emission towards free space. The dependence of the terahertz emission
      on the Pt-layer thickness is investigated. To optimize the geometry structure of
      the new type of emitter, we developed the theoretical model by carefully
      analyzing the spin transport. Our model reveals the importance to take into
      account the interfacial spin loss. It can be used to analyze more complex
      heterostructures.

PMID- 30114775
TI  - Quantum-limited directional amplifier based on a triple-cavity optomechanical
      system.
AB  - We theoretically propose a scheme for realizing a quantum-limited directional
      amplifier in a triple-cavity optomechanical system, where one microwave cavity
      and two optical cavities are, respectively, coupled to a common mechanical
      resonator. Moreover, the two optical cavities are coupled directly to facilitate
      the directional amplification between microwave and optical photons. We find that
      directional amplification between the three cavity modes is achieved with two
      gain process and one conversion process, and the direction of amplification can
      be modulated by controlling the phase difference between the field-enhanced
      optomechanical coupling strengths. Furthermore, with increasing the
      optomechanical cooperativity, both gain and bandwidth of the directional
      amplifier can be enhanced, and the noise added to the amplifier can be suppressed
      to approach the standard quantum limit on the phase-preserving linear amplifier.

PMID- 30114776
TI  - Upper temperature limit and multi-channel effects in ellipsoidal lithium-niobate
      optical parametric oscillators.
AB  - This paper theoretically investigated type-I optical parametric oscillations
      (OPOs) in lithium niobate (LN) ellipsoidal microcavities. We calculated the
      dependence of signal (idler) wavelength on temperature and found that multiple
      OPO channels are universal phenomenon in LN whispering gallery mode (WGM)
      microcavities. Additionally, We discovered OPOs in LN WGM microcavities, instead
      of having a lower-temperature limit, have an upper-temperature limit beyond which
      no OPO takes place. The dependence of the OPO tuning behaviors on the cavity
      geometry and pump wavelength was discussed systematically. Our investigations
      provide new conceptions for OPOs in LN WGM microcavities and may benefit the
      research on tunable laser sources or high-order entangled photon sources.

PMID- 30114777
TI  - Flat-field illumination for quantitative fluorescence imaging.
AB  - The uneven illumination of a Gaussian profile makes quantitative analysis highly
      challenging in laser-based wide-field fluorescence microscopy. Here we present
      flat-field illumination (FFI) where the Gaussian beam is reshaped into a uniform
      flat-top profile using a high-precision refractive optical component. The long
      working distance and high spatial coherence of FFI allows us to accomplish
      uniform epi and TIRF illumination for multi-color single-molecule imaging. In
      addition, high-throughput borderless imaging is demonstrated with minimal image
      overlap.

PMID- 30114778
TI  - Three-dimensional long-period waveguide gratings for mode-division-multiplexing
      applications.
AB  - We propose a three-dimensional (3D) long-period grating structure that has a
      controllable grating width and depth and can be formed at any chosen position on
      the surface of a waveguide core with a single photolithography process. The
      process relies on the partial etching of small structures on the surface of a
      polymer waveguide through a waveguide mask with narrow apertures that define the
      grating pattern. The 3D grating structure allows the design of mode converters
      for any nondegenerate guided modes of a waveguide, regardless of their symmetry
      properties, and thus relaxes the design constraint of conventional two
      dimensional waveguide gratings. To show the flexibility of the 3D grating
      structure, we present several mode converters fabricated with this structure. The
      mode-conversion efficiencies achieved are higher than 90% at the resonance
      wavelengths. In addition, we demonstrate a three-mode multiplexer by integrating
      a grating-based mode converter with two asymmetric directional couplers. The
      proposed grating structure together with the fabrication process can greatly
      facilitate the development of grating-based devices, especially for MDM
      applications.

PMID- 30114779
TI  - Bidirectional ring amplifier with twin pulses for high-power lasers.
AB  - A novel bidirectional ring amplifier with twin pulses for high-power lasers is
      proposed, and the performances on output energy capability and extraction
      efficiency are comprehended with detailed simulation. The results show that an
      extraction efficiency of 62.3% and the output energy of 13.4 kJ per pulse at the
      B integral limit can be obtained at low average fluence of 10.3 J/cm2 and the low
      injection energy of 3.9 mJ in the bidirectional ring amplifier. Compared with the
      multi-pass amplifier, the bidirectional ring amplifier is more compact and the
      extraction efficiency is much higher at low injection energy and low laser
      fluence operation, which is beneficial to simplify the preamplifier system and
      reduce the effects of nonlinear phase shift.

PMID- 30114780
TI  - Investigation of deep level defects on Beryllium compensation doping of
      In0.53Ga0.47As/GaAs0.49Sb0.51 type-II superlattice photodiodes.
AB  - In this paper, deep level transient spectroscopy (DLTS) characterization was
      performed on Beryllium compensation doping of InGaAs/GaAsSb type-II superlattice
      photodiode. Three electron traps with the energy levels located at Ec-0.11 eV
      (E1), Ec-0.28 eV (E2), Ec-0.17 eV (E3), and a hole trap situated at Ev + 0.25 eV
      (H1) were revealed. The position distribution and depth concentration of these
      traps in SL absorption region was also explored. Furthermore, the bandlike states
      (E2) and localized states (E1 and H1) of extended defects were confirmed by DLTS
      measurements as a function of the filling-pulse time, these traps as generation
      recombination centers are responsible for dominant dark current.

PMID- 30114781
TI  - Learned phase coded aperture for the benefit of depth of field extension.
AB  - Modern consumer electronics market dictates the need for small-scale and high
      performance cameras. Such designs involve trade-offs between various system
      parameters. In such trade-offs, Depth Of Field (DOF) is a significant issue very
      often. We propose a computational imaging-based technique to overcome DOF
      limitations. Our approach is based on the synergy between a simple phase aperture
      coding element and a convolutional neural network (CNN). The phase element,
      designed for DOF extension using color diversity in the imaging system response,
      causes chromatic variations by creating a different defocus blur for each color
      channel of the image. The phase-mask is designed such that the CNN model is able
      to restore from the coded image an all-in-focus image easily. This is achieved by
      using a joint end-to-end training of both the phase element and the CNN
      parameters using backpropagation. The proposed approach provides superior
      performance to other methods in simulations as well as in real-world scenes.

PMID- 30114782
TI  - Few-mode multicore fiber enabled integrated Mach-Zehnder interferometers for
      temperature and strain discrimination.
AB  - We proposed and experimentally demonstrated paralleled Mach-Zehnder
      interferometers (MZIs) in few-mode multicore fiber (FM-MCF) for temperature and
      strain discriminative sensing. A section of FM-MCF is sandwich-spliced between
      two single-mode multicore fiber (SM-MCF) with a rotational offset. The
      arbitrarily controlled angular misalignment generates intentional intermodal
      interferences in outer cores of the FM-MCF thus multiple MZI structures are
      implemented. Experimental results show that the temperature sensitivities are
      105.8 pm/ degrees C and 223.6 pm/ degrees C for two outer cores, strain
      sensitivity is 13.96 pm/MUepsilon for the outer core 1 and 11.7 pm/MUepsilon for
      the outer core 2, respectively. Due to the low condition number of the cross
      coefficient matrix dependent on the temperature and strain response indexes, the
      temperature-strain cross sensitivity can be efficiently eliminated. In addition,
      the structure's fabrication process is simple, cost effective, and repeatable.
      The sensing structure can be applied to a wide range of measurements and is
      expected to develop potentials by building a higher dimensional matrix with more
      cores.

PMID- 30114783
TI  - Tailoring terahertz surface plasmon wave through free-standing multi-walled
      carbon nanotubes metasurface.
AB  - Surface plasmons have a fundamental role in the dynamics of photon-electron
      interactions and in optical metamaterials. Terahertz (THz) time-domain
      spectroscopy was used to characterize the complex dielectric constant, index of
      refraction, and conductivity of super-aligned, free-standing, multi-walled carbon
      nanotube films over the range 0.2-2.5 THz. These complex parameters were in
      excellent agreement with Maxwell-Garnett and Drude-Lorentz models. In addition,
      surface plasmon excitations in engineered, subwavelength, multi-walled carbon
      nanotube metasurfaces were examined. The observed surface plasmon resonances,
      reproduced by simulation, could be changed over the THz frequency range by
      altering the lattice constant of the arrays. The THz transmission was enhanced at
      the resonance peak. Overall, the results indicate potential applications for THz
      metasurfaces based on super-aligned, free-standing multi-walled carbon nanotubes.

PMID- 30114784
TI  - Large angle beam steering THz antenna using active frequency selective surface
      based on hybrid graphene-gold structure.
AB  - Numerous studies have been made to design pattern reconfigurable THz antennas to
      achieve optimum performance for particular environmental conditions. However, it
      is still a challenge to achieve large angle beam steering for reconfigurable
      antenna in terahertz band. Here we propose a 360-degree beam steering THz antenna
      using active frequency selective surface (AFSS) based on hybrid graphene-gold
      structure. The proposed antenna consists of a THz omnidirectional monopole
      antenna coated with a hexagonal AFSS screen. By adjusting the chemical potential
      of graphene from 0 to 0.5eV, the AFSS unit cell can be switched from ON state
      (high transmission) to OFF state (total reflection) in terahertz, which can steer
      the beam direction as the monopole antenna is surrounded with six parts of AFSS
      screen with different ON/OFF states. In this way, the antenna can achieve beam
      scanning covering 360 degrees. Moreover, unlike the conventional AFSS with only
      two states, the reflection and transmission coefficient of the proposed AFSS are
      continuously variable due to the tunable chemical potential, which allows the
      radiation gain of antenna to be enlarged or suppressed. This antenna may serve
      the reconfigurable THz wireless system with flexible beam direction and gain
      level.

PMID- 30114785
TI  - 3D printed fiber optic faceplates by custom controlled fused deposition modeling.
AB  - A 3D printing technique for manufacturing air-clad coherent fiber optic
      faceplates is presented. The custom G-code programming is implemented on a fused
      deposition modeling (FDM) desktop printer to additively draw optical fibers using
      high-transparency thermoplastic filaments. The 3D printed faceplate consists of
      20000 fibers and achieves spatial resolution 1.78 LP/mm. Transmission loss and
      crosstalk are characterized and compared among the faceplates printed from four
      kinds of transparent filaments as well as different faceplate thicknesses. The
      printing temperature is verified by testing the transmission of the faceplates
      printed under different temperatures. Compared with the conventional stack-and
      draw fabrication, the FDM 3D printing technique simplifies the fabrication
      procedure. The ability to draw fibers with arbitrary organization, structure and
      overall shape provides additional degree of freedom to opto-mechanical design.
      Our results indicate a promising capability of 3D printing as the manufacturing
      technology for fiber optical devices.

PMID- 30114786
TI  - Fast light in the generation configuration of stimulated Brillouin scattering
      based on high-Q micro-cavities.
AB  - In this article, we reported self-pumped stimulated Brillouin scattering (SBS)
      induced fast light in a micro-resonator. The optically induced thermal effect in
      the micro-resonator will lead to a shift of the dispersion spectrum and make the
      SBS gain occurred in the anomalous dispersion regime. The group delay could be
      experimentally optimized from -91.0 microsecond to 2.6 microsecond by changing
      the modulation frequency in a microsphere with its diameter of 175 MUm. The
      experimental results will benefit applications utilizing anomalous dispersion
      such as gyroscope.

PMID- 30114787
TI  - Self-suppression of common-mode noises of the different fiber optic
      interferometric accelerometers.
AB  - This study proposes two new fiber optic interferometric accelerometers with the
      utilization of the push-pull structure, one is based on the principle of triple
      low-reflectivity fiber Bragg gratings, and the other is based on the 1x3
      unbalanced Michelson interferometer. The proposed accelerometers are capable of
      suppressing the common-mode noises (CMNs) by themselves without additional
      reference accelerometers, and therefore reducing the volume and the cost of the
      sensing system. Besides, the accelerometers can also suppress the sensor noises
      caused by the environment, and therefore show better CMNs suppression effect than
      the traditional method of using the reference accelerometer. The two
      accelerometers are experimentally verified and show respectively an improvement
      of 33 dB and 28 dB in CMNs suppression at 100 Hz. Both presented fiber optic
      accelerometers show huge advantages for the large-scale quasi-distributed oil and
      gas reservoir monitoring applications.

PMID- 30114788
TI  - Enhanced adaptive DA-ML carrier phase estimator and its application to accurate
      laser linewidth and SNR estimation.
AB  - We proposed a novel adaptive carrier phase estimator based on the phase
      information of the received signal only. Through eliminating the perturbation due
      to the amplitude of the AWGN, the proposed method outperforms the conventional
      adaptive filter in terms of both the carrier phase estimation and the filter gain
      tracking. Additionally, a dynamic tracking of both the laser linewidth and SNR is
      derived based on the proposed carrier phase estimator which requires no prior
      knowledge of the channel parameters. Numerical simulations and experiments are
      conducted to verify its feasibility in real applications.

PMID- 30114789
TI  - Pupil mask diversity for image correction in microscopy.
AB  - Three-dimensional microscopy suffers from sample-induced aberrations that reduce
      the resolution and lead to misinterpretations of the object distribution. In this
      paper, the resolution of a three-dimensional fluorescent microscope is
      significantly improved by introducing an amplitude diversity in the form of a
      binary amplitude mask positioned in several different orientations within the
      pupil, followed by computer processing of the diversity images. The method has
      proved to be fast, easy to implement, and cost-effective in high-resolution
      imaging of casper fli:GFP zebrafish.

PMID- 30114790
TI  - Scheimpflug Lidar for combustion diagnostics.
AB  - A portable Lidar system developed for large-scale (~1-20 m) combustion
      diagnostics is described and demonstrated. The system is able to perform remote
      backscattering measurements with range and temporal resolution. The range
      resolution is obtained by sharply imaging a part of the laser beam onto a CMOS
      array or ICCD detector. The large focal depth required to do this is attained by
      placing the laser beam, the collection optics and the detector in a so-called
      Scheimpflug configuration. Results from simulations of the range capabilities and
      range resolution of the system are presented and its temporal resolution is also
      discussed. Various applications, important for combustion diagnostics, are also
      demonstrated, including Rayleigh scattering thermometry, aerosol detection and
      laser-induced fluorescence measurements. These measurements have been carried out
      using various continuous-wave GaN diode lasers, emitting in the violet-blue (405 
      450 nm) wavelength regime. It is anticipated that Scheimpflug Lidar will provide
      a useful and versatile diagnostic tool for combustion research, not only for
      fundamental studies, but in particular for applications at industrial sites.

PMID- 30114791
TI  - Ultra-sensitive mid-infrared emission spectrometer with sub-ns temporal
      resolution.
AB  - We evaluate the performance of a mid-infrared emission spectrometer operating at
      wavelengths between 1.5 and 6 MUm based on an amorphous tungsten silicide (a-WSi)
      superconducting nanowire single-photon detector (SNSPD). We performed laser
      induced fluorescence spectroscopy of surface adsorbates with sub-monolayer
      sensitivity and sub-nanosecond temporal resolution. We discuss possible future
      improvements of the SNSPD-based infrared emission spectrometer and its potential
      applications in molecular science.

PMID- 30114792
TI  - Carrier dynamics of InxGa1-xN/GaN multiple quantum wells grown on (-201) beta
      Ga2O3 for bright vertical light emitting diodes.
AB  - High-quality InxGa1-xN/GaN multi-quantum well (MQW) structures (0.05<=x<=0.13),
      are successfully grown on transparent and conductive (-201)-oriented beta-Ga2O3
      substrate. Scanning-transmission electron microscopy and secondary ion mass
      spectrometry (SIMS) show well-defined high quality MQWs, while the In and Ga
      compositions in the wells and the barriers are estimated by SIMS. Temperature
      dependant Photoluminescence (PL) confirms high optical quality with a strong
      bandedge emission and negligble yellow band. time-resolved PL measurements (via
      above/below-GaN bandgap excitations) explain carrier dynamics, showing that the
      radiative recombination is predominant. Our results demonstrate that (-201)
      oriented beta-Ga2O3 is a strong candidate as a substrate for III-nitride-based
      vertical- emitting devices.

PMID- 30114793
TI  - Reconfigurable optical-microwave filter banks using thermo-optically tuned Bragg
      Mach-Zehnder devices.
AB  - A new reconfigurable, tunable on-chip optical filter bank is proposed and
      analyzed for the silicon-on-insulator platform at the ~1550 nm wavelength. The
      waveguided bank is a cascade connection of 2 x 2 Mach-Zehnder interferometer
      (MZI) filters. An identical standing-wave resonator is situated in each MZI
      "arm." Using the thermo-optic (TO) effect to perturb this waveguide's index, the
      TO heater stripes provide continuous tuning of the filter by shifting the
      resonance smoothly along the wavelength axis. To reconfigure and program the
      cascade array, a broadband 2 x 2 MZI-related switch is inserted between adjacent
      filters. The novel TO switch, described here, can provide either single or double
      interconnection of 2 x 2 filters. The filter resonator is a new in-guide array of
      N closely coupled phase-shifted Bragg-grating resonators that provide one
      resonant spectral profile with 5 to 100 GHz bandwidth. The length of each grating
      cavity in the N group is chosen according to the Butterworth filter technique,
      and this gives high peak transmission for the composite. The predicted spectral
      profiles of a three-stage cascade show two-or-three peaks, or two-or-three
      notches with movable wavelength-locations as well as tunable wavelength
      separations between those features. A tunable notch within a wider movable
      passband is also feasible. Potential applications include microwave photonics,
      wavelength-selective systems, optical spectroscopy and optical sensing.

PMID- 30114794
TI  - Abrupt-tapered fiber filter arrangement for a switchable multi-wavelength and
      tunable Tm-doped fiber laser.
AB  - A switchable and tunable multi-wavelength Tm-doped fiber laser is successfully
      demonstrated using a filter constructed with two tapered fiber elements in the
      cavity. The proposed system design uses a low-cost simple filter that allows
      stable dual, triple, quadruple, and quintuple-wavelength emission operation in
      the region around 1.9 MUm. In the dual wavelength regime, the laser is capable of
      independently tuning each wavelength. For switching and tuning, a curvature is
      applied to the tapered fibers.

PMID- 30114795
TI  - Closed-loop superluminal passive cavity.
AB  - We demonstrate the operation of a closed-loop fast-light cavity that allows rapid
      (~10 ms) measurements of the cavity mode frequency and its uncertainty. We vary
      the scale factor by temperature tuning the atomic density of an intracavity vapor
      cell. The cavity remains locked even as the system passes through the critical
      anomalous dispersion where a pole is observed in the scale factor. Positive and
      negative scale-factor enhancements as large as |S| ~70 were obtained. To our
      knowledge, these are the first experiments that demonstrate a scale-factor
      enhancement in a closed-loop fast-light device by changing the optical path
      length, laying the groundwork for the improvement of cavity-based metrology
      instruments such as optical gyroscopes.

PMID- 30114796
TI  - X-ray ptychography using randomized zone plates.
AB  - We have developed a randomized grating condenser zone plate (GCZP) that provides
      a um-scale probe for use in x-ray ptychography. This delivers a significantly
      better x-ray throughput than probes defined by pinhole apertures, while providing
      a clearly-defined level of phase diversity to the illumination on the sample, and
      helping to reduce the dynamic range of the detected signal by spreading the zero
      order light over an extended area of the detector. The first use of this novel x
      ray optical element has been demonstrated successfully for both amplitude and
      phase contrast imaging using soft x-rays on the TwinMic beamline at the Elettra
      synchrotron.

PMID- 30114797
TI  - Diode-pumped alexandrite ring laser in single-longitudinal mode operation for
      atmospheric lidar measurements.
AB  - We present, to the best of our knowledge, design and performance data of the
      first diode-pumped Alexandrite ring laser in Q-switched single-longitudinal mode
      (SLM) operation. The laser resonator contains two Alexandrite crystals, which are
      pumped longitudinally by means of two laser diode-bar modules emitting at 636 nm.
      Single-longitudinal mode operation is achieved by seeding the laser with a diode
      laser operating in SLM and actively stabilizing the cavity, yielding a linewidth
      of < 10 MHz at the potassium resonance line at 770 nm. The pulse energy is 1 mJ
      at a repetition rate of 150 Hz and 0.65 mJ at 320 Hz. The beam quality of M2 <
      1.2 in both directions remains unchanged for the different repetition rates.
      After characterization in the laboratory, the laser was implemented in a novel
      mobile lidar system and first atmospheric measurements were conducted
      successfully.

PMID- 30114798
TI  - Replication of a glass microlens array using a vitreous carbon mold.
AB  - A low-cost fabrication method for a high-surface-quality glass microlens array
      (MLA) was proposed using a glass molding technique with a vitreous carbon (VC)
      mold. A VC mold with a high-surface-quality MLA cavity was fabricated, and the
      glass MLA with a root mean square surface roughness of 4.59 nm was replicated
      using the VC mold. To obtain the glass MLA with high replication quality, the
      effects of molding conditions were examined. The surface quality was not degraded
      during the proposed VC mold fabrication method and glass molding process. The
      focused beam spot of the glass molded MLA was analyzed; it showed a diffraction
      limited characteristic of the glass molded MLA.

PMID- 30114799
TI  - Spatially-distributed orbital angular momentum beam array generation based on
      greedy algorithms and coherent combining technology.
AB  - A novel approach to generate a spatially-distributed orbital angular momentum
      (OAM) beam array based on coherent combining technology is presented. The
      arrangement of the multiple fundamental Gaussian beams at the initial plane, as
      well as the intensity weights and the phase distributions of the array beams, is
      determined by the reversal of Huygens Fresnel diffraction and the greedy
      algorithm. This method ensures that a vortex beam array is formed at a specified
      distance, and the distance can be adjusted by phase modulation. The evolution
      properties of the synthesized beam array near the receiver plane are studied as
      well to estimate the robustness of the method. The experimental limitations of
      this technique are discussed, including the maximum number of beams, the relative
      separation of each beam and the maximum topological charges. The results
      illustrate that a spatially-distributed OAM beam array can be effectively
      generated within a finite distance interval, and the distance is adjustable. This
      new method enables further applications of a structured optical field, such as
      optical communication and spatial light structuring.

PMID- 30114800
TI  - Mach-Zehnder crossbar switching and tunable filtering using N-coupled waveguide
      Bragg resonators.
AB  - This theoretical modeling-and-simulation paper presents designs and projected
      performance of ~1500-nm silicon-on-insulator 2 x 2 Mach-Zehnder interferometer
      (MZI) optical crossbar switches and tunable filters that are actuated by thermo
      optical (TO) means. A TO heater stripe is assumed to be on the top of each
      waveguided arm in the interferometer. Each strip-waveguide arm contains an inline
      set of N-fold coupled, phase-shifted Bragg-grating resonators. To implement
      accurate and realistic designs, a mixed full-vectorial mathematical model based
      upon the finite-element, coupled-mode, and transfer-matrix approaches was
      employed. The Butterworth-filter technique for grating length and weighting was
      used. The resulting narrowband waveguide-transmission spectral shape was better
      than-Lorentzian because of its steeper sidewalls (faster rolloff). The metrics of
      crossbar switching, insertion loss (IL) and crosstalk (CT), were evaluated for
      choices of grating strength and TO-induced change in the grating-waveguide
      refractive index. The predicted ILs and CTs were quite superior to those cited in
      the literature for experimental and theoretical MZI devices based upon silicon
      nanobeam resonators. This was true for the Type-I and Type-II resonator
      addressing discussed here. Finally, we examined the TO-tunable composite filter
      profiles that are feasible by connecting two or more Type-I MZIs in an optical
      series arrangement. A variety of narrow filter shapes, tunable over ~2 nm, was
      found.

PMID- 30114801
TI  - Inline fiber optic power sensor featuring a variable tap ratio based on a tightly
      focused femtosecond laser inscription.
AB  - We propose and demonstrate an inline fiber optic power sensor (IFPS) resorting to
      an embedded waveguide tap, which is formed to traverse across the cladding and
      core of a standard single-mode fiber. The tap was produced via a single-step
      inscription based on the femtosecond laser direct-writing method. A tightly
      focused pulsed laser beam has been particularly exploited to suppress the
      elongation along the laser propagation direction, thereby improving the cross
      sectional symmetry of the created tap waveguide. The fabricated fiber optic tap
      has been stably combined with a photodiode via a compact package. The achieved
      tap ratio could be tuned from 1.0% to 5.9% at the wavelength of 1550 nm by
      adjusting the applied laser power, while the induced excess loss was kept below
      0.6 dB. The proposed IFPS will be highly suitable for real-time power monitoring
      in a variety of applications, including optical communication networks and
      systems.

PMID- 30114802
TI  - Fast fully-integrated front-end circuit to overcome pile-up limits in time
      correlated single photon counting with single photon avalanche diodes.
AB  - Time-Correlated Single Photon Counting (TCSPC) is an essential tool in many
      scientific applications, where the recording of optical pulses with picosecond
      precision is required. Unfortunately, a key issue has to be faced: distortion
      phenomena can affect TCSPC experiments at high count rates. In order to avoid
      this problem, TCSPC experiments have been commonly carried out by limiting the
      maximum operating frequency of a measurement channel below 5% of the excitation
      frequency, leading to a long acquisition time. Recently, it has been demonstrated
      that matching the detector dead time to the excitation period allows to keep
      distortion around zero regardless of the rate of impinging photons. This solution
      paves the way to unprecedented measurement speed in TCSPC experiments. In this
      scenario, the front-end circuits that drive the detector play a crucial role in
      determining the performance of the system, both in terms of measurement speed and
      timing performance. Here we present two fully integrated front-end circuits for
      Single Photon Avalanche Diodes (SPADs): a fast Active Quenching Circuit (AQC) and
      a fully-differential current pick-up circuit. The AQC can apply very fast voltage
      variations, as short as 1.6ns, to reset external custom-technology SPAD
      detectors. A fast reset, indeed, is a key parameter to maximize the measurement
      speed. The current pick-up circuit is based on a fully differential structure
      which allows unprecedented rejection of disturbances that typically affect SPAD
      based systems at the end of the dead time. The circuit permits to sense the
      current edge resulting from a photon detection with picosecond accuracy and
      precision even a few picoseconds after the end of the dead time imposed by the
      AQC. This is a crucial requirement when the system is operated at high rates.
      Both circuits have been deeply characterized, especially in terms of achievable
      measurement speed and timing performance.

PMID- 30114803
TI  - Pump distribution effect in dual-wavelength Raman-erbium random distributed
      feedback fiber laser.
AB  - This work demonstrates a simple dual-wavelength random distributed feedback fiber
      laser via excitation of the Raman-erbium hybrid gain by a single pump source.
      Lasing wavelengths at 1568 nm and 1595 nm with 48.48 dBm maximum OSNR were
      generated without the need for physical reflectors. Enhancements were performed
      using pump power distribution and a seeded feedback to reduce the peak disparity
      to only 0.16 dB. The long cavity hybrid random laser with its balanced and
      broadly spaced dual-wavelength output offers immense potential for long distance
      dual laser applications.

PMID- 30114804
TI  - Frequency-modulated continuous-wave LiDAR compressive depth-mapping.
AB  - We present an inexpensive architecture for converting a frequency-modulated
      continuous-wave LiDAR system into a compressive-sensing based depth-mapping
      camera. Instead of raster scanning to obtain depth-maps, compressive sensing is
      used to significantly reduce the number of measurements. Ideally, our approach
      requires two difference detectors. Due to the large flux entering the detectors,
      the signal amplification from heterodyne detection, and the effects of background
      subtraction from compressive sensing, the system can obtain higher signal-to
      noise ratios over detector-array based schemes while scanning a scene faster than
      is possible through raster-scanning. Moreover, by efficiently storing only 2m
      data points from m < n measurements of an n pixel scene, we can easily extract
      depths by solving only two linear equations with efficient convex-optimization
      methods.

PMID- 30114805
TI  - Dual-feedback mid-infrared cavity-enhanced absorption spectroscopy for H2CO
      detection using a radio-frequency electrically-modulated interband cascade laser.
AB  - A mid-infrared cavity-enhanced sensor system was demonstrated for the detection
      of formaldehyde (H2CO) using a continuous-wave (cw) interband cascade laser (ICL)
      centered at 3599 nm. A compact Fabry-Perot (F-P) cavity with a physical size of
      38 * 52 * 76 mm3 was developed consisting of two concave mirrors with a radius of
      curvature of 80 mm and a reflectivity of 99.8% at 3.6 MUm. Different from the
      widely reported electro-optical (EO) external modulation based Pound-Drever-Hall
      (PDH) locking technique, a radio-frequency electrical internal modulation based
      PDH technique was used for locking the laser mode to the cavity mode. A dual
      feedback control on the laser current and on the piezo transducer (PZT)
      displacement was utilized for further stabilizing mode locking. A 20 m effective
      optical path length was achieved with a cavity length of 2 cm and a finesse of
      1572. The effectiveness and sensitivity of the sensor system were demonstrated by
      targeting an absorption line at 2778.5 cm-1 for H2CO measurements. A linear
      relation between the cavity transmitted signal amplitude and the H2CO
      concentration was obtained within the range of 0-5 ppm. A 1sigma detection limit
      of 25 parts-per-billion (ppb) was achieved with an averaging time of 1 s based on
      Allan-Werle variance analysis. The reported dual-feedback RF modulation based PDH
      technique led to a method for gas detection using a similar experimental setup
      and measurement scheme.

PMID- 30114806
TI  - Waveguide-based electro-absorption modulator performance: comparative analysis.
AB  - Electro-optic modulators perform a key function for data processing and
      communication. Rapid growth in data volume and increasing bits per second rates
      demand increased transmitter and thus modulator performance. Recent years have
      seen the introduction of new materials and modulator designs to include
      polaritonic optical modes aimed at achieving advanced performance in terms of
      speed, energy efficiency, and footprint. Such ad hoc modulator designs, however,
      leave a universal design for these novel material classes of devices missing.
      Here we execute a holistic performance analysis for waveguide-based electro
      absorption modulators and use the performance metric switching energy per unit
      bandwidth (speed). We show that the performance is fundamentally determined by
      the ratio of the differential absorption cross-section of the switching
      material's broadening and the waveguide effective mode area. We find that the
      former shows highest performance for a broad class of materials relying on Pauli
      blocking (absorption saturation), such as semiconductor quantum wells, quantum
      dots, graphene, and other 2D materials, but is quite similar amongst these
      classes. In this respect these materials are clearly superior to those relying on
      free carrier absorption, such as Si and ITO. The performance improvement on the
      material side is fundamentally limited by the oscillator sum rule and thermal
      broadening of the Fermi-Dirac distribution. We also find that performance scales
      with modal waveguide confinement. Thus, we find highest energy-bandwidth-ratio
      modulator designs to be graphene, QD, QW, or 2D material-based plasmonic slot
      waveguides where the electric field is in-plane with the switching material
      dimension. We show that this improvement always comes at the expense of increased
      insertion loss. Incorporating fundamental device physics, design trade-offs, and
      resulting performance, this analysis aims to guide future experimental modulator
      explorations.

PMID- 30114808
TI  - Experimental study of performance enhanced IM/DD transmissions based on
      constellation switching.
AB  - In this work, we experimentally investigate the performance improvement in IM/DD
      systems using constellation switching (CS), which is simple to implement with a
      reasonably low complexity. By encoding extra bits on the selection of a PAM
      constellation pattern from a set of constellations, a lower symbol rate can be
      used to achieve the same system bit rate compared with standard PAM systems based
      on a single constellation pattern. In our experiments with bandwidth limited
      components, including a 14 GHz bandwidth digital-to-analog converter (DAC), we
      demonstrate that the CS signals can improve the receiver sensitivity. In
      particular, in the 112 Gbit/s PAM4 case, the required receiver power was reduced
      by 0.8 dB and 1.1 dB using the CS at the HD FEC threshold of BER = 4 * 10-3 in
      the back-to-back (B2B) and 3 km fiber transmission, respectively. Similarly, in
      the 84 Gbit/s two-dimension (2D) PAM4 case, the required receiver power was
      reduced by 1.05 dB and 3.5 dB at the HD FEC threshold of BER = 4 * 10-3 in the
      back-to-back (B2B) and 5 km fiber transmission, respectively. Moreover, we show
      by simulations that the improved performance of using the CS signals is also
      observed over a wide range of transmitter bandwidth, further indicating the
      merits of using the CS in IM/DD PAM transmissions.

PMID- 30114807
TI  - Orbital angular momentum modes emission from a silicon photonic integrated device
      for km-scale data-carrying fiber transmission.
AB  - We experimentally demonstrate orbital angular momentum (OAM) modes emission from
      a high emission efficiency OAM emitter for 20-Gbit/s quadrature phase-shift
      keying (QPSK) carrying data transmission in few-mode fiber (FMF). The device is
      capable of emitting vector optical vortices carrying well-defined OAM efficiently
      with the efficiency of the device >37%. Seven modes propagate through a 2-km two
      mode and a 3.6-km three-mode FMF with measured optical signal-to-noise ratio
      (OSNR) penalties less than 4 dB at a bit-error rate (BER) of 2 * 10-3. The
      demonstrations with favorable performance pave the way to incorporate silicon
      photonic integrated devices as transceivers in an OAM-enabled optical fiber
      communication link.

PMID- 30114809
TI  - Manipulation of extinction features in frequency combs through the usage of
      graphene.
AB  - Lately, the integration of two-dimensional materials into semiconductor devices
      has allowed the modification of their effective index by simply applying a modest
      voltage (between 0 and 3 volts). In this work, we present a device composed of
      two evanescently coupled silicon microring resonators where both rings have a
      graphene layer on top. This design is aimed to produce frequency combs with
      transmission characteristics controlled upon voltage application to the graphene
      layer. We numerically analyze the device response as a function of the incident
      wavelength and applied voltage. The results showed a low input intensity (0.6
      GW/cm2) needed and a rapid response time (0.1 MUs), in comparison to devices
      controlled by heat injection.

PMID- 30114810
TI  - Hamiltonian approach for optimization of phase-sensitive double-pumped parametric
      amplifiers.
AB  - In this work we applied a Hamiltonian formalism to simplify the equations of non
      degenerate nonlinear four-wave mixing to the one-degree-of-freedom Hamiltonian
      equations with a three-parameter Hamiltonian. Thereby, a problem of signal
      amplification in a phase-sensitive double-pumped parametric fiber amplifier with
      pump depletion was reduced to a geometrical study of the phase portraits of the
      one-degree-of-freedom Hamiltonian system. For a symmetric case of equal pump
      powers and equal signal and idler powers at the fiber input, it has been shown
      that the theoretical maximum gain occurs on the extremal trajectories. However,
      to reduce the nonlinear interaction of waves, we proposed to choose the
      separatrix as the optimal trajectory on the phase plane. Analytical expressions
      were found for the maximum amplification, as well as the length of optical fiber
      and the relative phase of interacting waves allowing this amplification. Using
      the proposed approach, we optimized of the phase-sensitive parametric amplifier.
      As a result, the optimal parameters of the phase-sensitive amplifier were found
      and the maximum possible signal amplification was realized in a broad range of
      signal wavelengths.

PMID- 30114811
TI  - Short-wave infrared compressive imaging of single photons.
AB  - We present a short-wave infrared (SWIR) single photon camera based on a single
      superconducting nanowire single photon detector (SNSPD) and compressive imaging.
      We show SWIR single photon imaging at a megapixel resolution with a low signal-to
      background ratio around 0.6, show SWIR video acquisition at 20 frames per second
      and 64x64 pixel video resolution, and demonstrate sub-nanosecond resolution time
      of-flight imaging. All scenes were sampled by detecting only a small number of
      photons for each compressive sampling matrix. In principle, our technique can be
      used for imaging faint objects in the mid-IR regime.

PMID- 30114812
TI  - Time-multiplexed multi-view three-dimensional display with projector array and
      steering screen.
AB  - A novel time-multiplexed multi-view three-dimensional (3D) display has been
      implemented using a projector array to provide the image source and an angular
      steering-screen module to generate multiple high density horizontal views. The
      liquid crystal (LC)-based steering screen was specially developed to deflect
      light beams over a small range and operate in synchronism with the projector
      array with the use of a customized FPGA driver. The prototype produces vivid
      color 3D scenes with smooth parallax to multiple viewers. The experimental
      results verify the proposed multi-projection time-multiplexed multi-view 3D
      display method that uses a steering screen to produce dense views. Displaying
      both static and dynamic 3D contents is achieved in our implemented 36-view 3D
      display prototype. The results of crosstalk measurements are given and analyzed
      to evaluate the display performance.

PMID- 30114813
TI  - Optical fibre-tip probes for SERS: numerical study for design considerations.
AB  - Enhancement of sub-wavelength optical fields using sub-micron plasmonic probes
      has found many applications in chemical, material, biological and medical
      sciences. The enhancement is via localised surface-plasmon resonance (LSPR) which
      enables the highly sensitive vibrational-spectroscopy technique of surface
      enhanced Raman scattering (SERS). Combining SERS with optical fibres can allow
      the monitoring of biochemical reactions in situ with high resolution. Here, we
      study the electromagnetic-field enhancement of a tapered optical fibre-tip coated
      with gold nanoparticles (AuNPs) using finite-element simulations. We investigate
      the electric-field enhancement associated with metallic NPs and study the effect
      of parameters such as tip-aperture radius, cone angle, nanoparticle size and gaps
      between them. Our study provides an understanding of the design and application
      of metal-nanoparticle-coated optical-fibre-tip probes for SERS. The approach of
      using fibre-coupled delivery adds flexibility and simplifies the system
      requirements in SERS, making it suitable for cellular imaging and mapping bio
      interfaces.

PMID- 30114814
TI  - Frequency comb generation in a quadratic nonlinear waveguide resonator.
AB  - Enhancement of a nonlinear optical interaction through waveguides or resonators
      disclose unconventional interplay among multiple lights. Microresonator-based
      optical frequency comb (OFC) generation via third order nonlinearity is a typical
      example of such enhancements. Recently, quadratic-nonlinearity-based OFC with an
      external cavity configuration has been found and its on-chip implementation is
      highly demanded. Here we for the first time demonstrate such an on-chip OFC with
      a quadratic nonlinear waveguide resonator. Furthermore, we controlled the comb
      spectra separation by adjusting frequency difference of two pump light. This on
      chip quadratic device will be useful for not only metrologies but also integrated
      quantum information technologies.

PMID- 30114815
TI  - Leaky property of the Dyakonov-like wave at the surface of a semi-infinite metal
      dielectric multilayered structure.
AB  - We investigate the Dyakonov-like surface wave (DLSW) at the interface of a
      dielectric and a metal-dielectric multilayered (MDM) structure when this MDM
      structure serves as an elliptic medium according to the effective medium
      approximation (EMA). Different from the conventional Dyakonov surface waves, we
      find that this kind of DLSW possesses an unexpected leaky property due to an
      additional hyperbolic-like wave in the MDM structure, resulting in a significant
      increase of propagation loss compared to the results estimated by a simple
      effective model based on the EMA. Moreover, such leaky property is found to be
      sensitive to the period of the MDM structure. Thus, to diminish this non
      negligible leaky loss, one can suppress the amplitude of the leaky component by
      designing the MDM structure with a smaller period. On the other hand, as the MDM
      structure sometimes can also support an additional elliptic-like dispersion when
      it is regarded as a hyperbolic medium, we discuss this condition for
      completeness. Based on this elliptic-like dispersion, an apparent leaky property
      is observed in the resultant DLSW. This DLSW propagates with a wider range of
      propagation direction but suffers from a poor field confinement to the interface
      it is propagating along.

PMID- 30114816
TI  - Investigation of spectral properties and lateral confinement of THz waves on a
      metal-rod-array-based photonic crystal waveguide.
AB  - Terahertz (THz) waves laterally confined in a 1 mm-thick microstructured planar
      waveguide are demonstrated on a free-standing metal rod array (MRA), and one
      apparent rejection band of a transmission spectrum, resembling the bandgap of a
      photonic crystal, is found in 0.1-0.6 THz. The visibility of the photonic bandgap
      in the spectral width and power distinction can be manipulated by changing the
      MRA geometry parameters, including the rod diameter, the interspace between
      adjacent rods, and the propagation length based on the interactive MRA-layer
      number. THz transmission ratio enhanced by a large interactive length is verified
      in 30 MRA layers due to the longitudinally resonant guidance of transverse
      magnetic-polarized waveguide modes along the MRA length, which is critical to the
      interspace width of adjacent rods and the metal coating of the rod surface. For
      an MRA with respective rod diameter and interspace dimensions of about 0.16 and
      0.26 mm, the highest transmission of the guided resonant THz waves are performed
      at 0.505-0.512 THz frequency with strong confinement on the metal rod tips and a
      low scattering loss of 0.003 cm-1.

PMID- 30114817
TI  - Nb5N6 microbolometer for sensitive, fast-response, 2-um detection.
AB  - Room-temperature thermal detection at a wavelength of 2 um in the short-wave
      infrared range (1.7-3 um) was demonstrated for the first time using a Nb5N6
      microbolometer. The photothermal responses of two types of Nb5N6 microbolometers
      were evaluated. By suspending Nb5N6 microwires in the air above the substrate, a
      reduction in thermal conductance of the device by a factor of 39 was achieved.
      The measured optical voltage responsivity RO of the Nb5N6 microbolometer reached
      the value of 61.5 V/W. A noise equivalent power of 8.5 * 10-11 W/?Hz (at 1 kHz)
      and a detectivity D* = 2.0 * 107 cm?Hz /W with a typical response time as small
      as 0.17 ms was obtained at a wavelength of 2 um for a 10 * 30-um2 device. The
      performance could be improved further by optimizing the design and operating
      parameters. This study revealed a simple low-cost technique to develop a large
      scale focal plane array in silicon for infrared detection.

PMID- 30114818
TI  - Hyperuniformity in amorphous speckle patterns.
AB  - Hyperuniform structures possess the ability to confine and drive light, although
      their fabrication is extremely challenging. Here we demonstrate that speckle
      patterns obtained by a superposition of randomly arranged sources of Bessel beams
      can be used to generate hyperunifrom scalar fields. By exploiting laser light
      tailored with a spatial filter, we experimentally produce (without requiring any
      computational power) a speckle pattern possessing maxima at locations
      corresponding to a hyperuniform distribution. By properly filtering out intensity
      fluctuation from the same speckle pattern, it is possible to retrieve an
      intensity profile satisfying the hyperuniformity requirements. Our findings are
      supported by extensive numerical simulations.

PMID- 30114819
TI  - Far-field propagation of partially coherent laser light in random mediums.
AB  - The irradiance of a partially coherent light propagated under the influence of
      multiple random effects is shown to be the convolution of the irradiance
      propagated in a vacuum with the system's point spread function representing the
      random effects. This is true regardless of whether the propagation is far-field
      or not. We also show that the far-field irradiance of any laser system,
      regardless of complexity, can be expressed in terms of three basic parameters;
      laser power, field area, and a pupil factor. A general analytical formula for the
      far-field irradiance distribution for partially coherent laser sources of any
      complexity is derived. The formula includes multiple random effects including
      strong turbulence, random beam jitter, partial coherence, in addition to laser
      system pupil effects. An efficient matrix based numerical solution is also
      developed to verify the accuracy of the formula. Applications to the propagation
      of clipped Gaussian or flat-top beams with an obscuration, both as a single beam
      or an array of beams, are shown to give accurate results over the whole range of
      weak to strong turbulence as compared to numerical modeling.

PMID- 30114820
TI  - Low-cost single-pixel 3D imaging by using an LED array.
AB  - We propose a method to perform color imaging with a single photodiode by using
      light structured illumination generated with a low-cost color LED array. The LED
      array is used to generate a sequence of color Hadamard patterns which are
      projected onto the object by a simple optical system while the photodiode records
      the light intensity. A field programmable gate array (FPGA) controls the LED
      panel allowing us to obtain high refresh rates up to 10 kHz. The system is
      extended to 3D imaging by simply adding a low number of photodiodes at different
      locations. The 3D shape of the object is obtained by using a non-calibrated
      photometric stereo technique. Experimental results are provided for an LED array
      with 32 * 32 elements.

PMID- 30114821
TI  - Core position alignment in polymer optical waveguides fabricated using the
      Mosquito method.
AB  - We fabricate multimode polymer optical waveguides with circular graded-index (GI)
      cores which are aligned in parallel at desired positions using the Mosquito
      method. In the Mosquito method, three-dimensional wiring patterns can be formed
      with a simple process. However, the core position is likely to deviate from the
      designed position because of multiple fabrication factors. Hence, in this paper,
      the dominant parameters to influence on the core height in the cladding are
      investigated both theoretically and experimentally. In particular, a linear
      relationship between the core height and the needle-tip height is confirmed with
      theoretical fluid analysis. Using this relationship, we succeeded in fabricating
      a waveguide in which the maximum variation of the core height from the designed
      value is controlled to be less than 10 um.

PMID- 30114822
TI  - Analysis and characterization of chaos generated by free-running and optically
      injected VCSELs.
AB  - We report on the dynamics of free-running and optically injected VCSELs. In
      particular, the powerful measures including the 0-1 test for chaos and
      permutation entropy are used for locating the chaotic dynamics in a free-running
      VCSEL, which illustrates the effects of some key parameters on the chaotic
      region. In order to enhance chaotic dynamics, the output of the free-running
      VCSEL (master) is injected to another free-running VCSEL (slave). Our results
      show that the chaotic dynamics of the slave VCSEL can be greatly enhanced, i.e.,
      both the bandwidth and complexity, while this occurs only outside of the
      injection locking region where the correlation between the mater and slave lasers
      is low. To take advantage of these enhanced chaotic dynamics exhibiting extremely
      high complexity and broadband bandwidth, a three-laser synchronization scheme is
      proposed and demonstrated. These findings pave the way to the generation of high
      quality chaos (no time-delay signature, high bandwidth and complexity) and
      notably chaos-based applications based on free-running and optically injected
      VCSELs.

PMID- 30114823
TI  - Quantum plasmonic epsilon near zero: field enhancement and cloaking.
AB  - We investigate the effect of the electron wave function producing permittivity
      (epsilon) near zero in sub-nanometer gaps and at surfaces. The field enhancement
      is calculated for gaps and nanoparticles, as well as the absorption from
      nanoparticles. Our modified quantum corrected model shows reduced absorption for
      nanoparticles due to "cloaking" of the epsilon near zero region, which has lower
      loss than the bulk region. We demonstrate that a modified quantum corrected model
      finite-difference time-domain simulation of metal slits with sub-nanometer gaps
      are in good agreement with the analytic expression for the quantum corrected
      plasmonic resonance wavelength as a function of gap size coming from Re{epsilon}
      = 0.

PMID- 30114824
TI  - Transparent broadband metamaterial absorber enhanced by water-substrate
      incorporation.
AB  - In this paper, a transparent metamaterial absorber (MA) loaded with water
      substrate is presented, which can simultaneously achieve enhanced broadband
      microwave absorption and tunable infrared radiation. As a proof, the indium tin
      oxide (ITO) films are first introduced here as a frequency selective surface
      (FSS) on the top layer and reflective backplane on the ground layer. Next the
      distilled water combined with the polymethyl methacrylate (PMMA) substrate is
      employed as a hybrid substrate in the middle. Simulation and experimental
      measurements show that the transparent water-substrate MA can achieve broadband
      microwave absorption with efficiency over 90% in the frequency band of 6.4
      23.7GHz, and the proposed hybrid substrate has almost no influence on its
      original transmittance. Moreover, owing to the available water circulation
      system, the infrared radiation of the proposed MA is also demonstrated to be
      controlled by the temperature of the injected water. Based on its multifunction
      and high performance, it is expected that the proposed design may find potential
      applications, such as glass window of stealth equipment, electromagnetic
      compatible buildings/facilities, etc.

PMID- 30114825
TI  - Universal modeling of second-order nonlinear frequency conversion in three
      dimensional nonlinear photonic crystals.
AB  - The second-order nonlinear frequency conversion in three-dimensional nonlinear
      photonic crystals is theoretically studied using coupled wave equations. A
      universal theoretical model is obtained, with a unified expression combining
      birefringence phase match, quasi-phase match, nonlinear Raman-Nath diffraction,
      nonlinear Cerenkov radiation and nonlinear Bragg diffraction. They are
      demonstrated in the numerical simulation. With the phase-matching conditions in
      lower dimensions extended to three dimensions, more various phenomena can be seen
      and corresponding mechanisms can be explained. This research enables the control
      of second-harmonic generation more efficiently and has potential applications in
      more complicated nonlinear photonic crystals.

PMID- 30114826
TI  - Generation of single or double parallel breathing soliton pairs, bound breathing
      solitons, moving breathing solitons, and diverse composite breathing solitons in
      optical fibers.
AB  - Interactions of two truncated Airy pulses with arbitrarily initial relative
      phases, initial pulse intervals, and different soliton order are numerically
      investigated in optical fibers. When the soliton order is 1, depending on
      different initial pulse intervals, the initial in-phase Airy pulses may evolve to
      single breathing solitons, bound breathing solitons, and single parallel
      breathing solitons. While the out-of-phase Airy pulses may evolve to parallel or
      repulsive soliton pairs with breathing or weak breathing, after radiating away
      some dispersive waves. When the initial relative phases take arbitrary values
      except 0 and pi, moving single breathing solitons and repulsive or parallel
      soliton pairs will form. Moreover, the whole temporal profiles may become
      asymmetric. The repulsive soliton pairs consist of two moving breathing solitons
      with different intensities, moving velocities, and breathing periods. The most
      interestingly is that, when the soliton order is larger than one, we observe
      double bound breathing solitons, double parallel breathing soliton pairs, and
      diverse composite breathing solitons which consist of two or more different
      breathing solitons. one can effectively manipulate and select the soliton
      expected and its evolution dynamics by adjusting the soliton order, initial pulse
      intervals, and initial relative phases.

PMID- 30114827
TI  - Numerical investigation of pulsed gas amplifiers operating in hollow-core optical
      fibers.
AB  - Optically pumped molecular gas amplifiers having a gain medium contained in a
      hollow-core optical fiber are investigated with numerical modeling to understand
      the primary physical processes that affect amplifier output and efficiency. A
      comparison of computational results with experimental measurements of incident
      pump, absorbed pump, and emitted mid-IR from a pulsed, acetylene-filled, hollow
      core fiber amplifier [ Opt. Exp.25, 13351 (2017)] is used to explore the effects
      of various physical processes on pulsed amplifier operation. Single frequency,
      one-dimensional, time-dependent models are shown to align with experimentally
      measured lasing thresholds and ratios of absorbed pump to emitted laser energy
      but significantly over predict the amount of incident pump energy that is
      absorbed. A two-dimensional, time-dependent model that assumes Gaussian spectral
      and radial intensity profiles for the pump is developed and shows an improved
      ability to capture pump absorption. Results indicate that 1D, time-dependent
      models have utility in guiding experiments but the significant influence of the
      pump and laser propagation modes and the pump spectral characteristics on
      efficiency, threshold, and signal output must be explicitly included in high
      fidelity high-power modeling.

PMID- 30114828
TI  - Continuous-wave and pulsed 1,066-nm Nd:Gd0.69Y0.3TaO4 laser directly pumped by a
      879-nm laser diode.
AB  - We demonstrated an 879-nm-diode-pumped Nd:Gd0.69Y0.3TaO4 laser in continuous-wave
      (CW), pulse-pumped, pulse-reflection-mode Q-switched, and cavity-dumped burst
      mode Q-switched operations for the first time. A maximum output power of 9.3 W at
      1,066 nm was obtained in the CW operation with a slope efficiency of ~48%. The
      slope efficiency reached the value of ~68% in the pulse-pumped operation. A peak
      power of 150 kW and pulse width of 3.4 ns were obtained in the cavity-dumped
      burst-mode Q-switched operation at a Q-switching repetition rate of 20 kHz.

PMID- 30114829
TI  - Enhanced performance of a multiband super-Nyquist CAP16 VLC system employing a
      joint MIMO equalizer.
AB  - In this paper, we have experimentally demonstrated the feasibility of a LMS
      Volterra based joint MIMO equalizer in multiband super-Nyquist carrierless
      amplitude phase modulation visible light communication system. To obtain higher
      spectrum efficiency, overlapping between different sub-bands is introduced in
      this experiment. By using joint MIMO equalizer, an aggregate data rate of 1.26
      Gb/s is successfully achieved in 1-m indoor free space transmission with the BER
      below the 7% FEC limit of 3.8 * 10-3. To our best knowledge, this is the first
      time that our proposed joint MIMO equalizer is used to equalize multiband super
      Nyquist data in VLC system.

PMID- 30114830
TI  - Temperature stability of thin film refractory plasmonic materials.
AB  - Materials such as W, TiN, and SrRuO3 (SRO) have been suggested as promising
      alternatives to Au and Ag in plasmonic applications owing to their stability at
      high operational temperatures. However, investigation of the reproducibility of
      the optical properties after thermal cycling between room and elevated
      temperatures is so far lacking. Here, thin films of W, Mo, Ti, TiN, TiON, Ag, Au,
      SrRuO3 and SrNbO3 are investigated to assess their viability for robust
      refractory plasmonic applications. These results are further compared to the
      performance of SrMoO3 reported in literature. Films ranging in thickness from 50
      to 105 nm are deposited on MgO, SrTiO3 and Si substrates by e-beam evaporation,
      RF magnetron sputtering and pulsed laser deposition, prior to characterisation by
      means of AFM, XRD, spectroscopic ellipsometry, and DC resistivity. Measurements
      are conducted before and after annealing in air at temperatures ranging from 300
      to 1000 degrees  C for one hour, to establish the maximum cycling temperature and
      potential longevity at elevated temperatures for each material. It is found that
      SrRuO3 retains metallic behaviour after annealing at 800 degrees  C, while SrNbO3
      undergoes a phase transition resulting in a loss of metallic behaviour after
      annealing at 400 degrees  C. Importantly, the optical properties of TiN and TiON
      are degraded as a result of oxidation and show a loss of metallic behaviour after
      annealing at 500 degrees  C, while the same is not observed in Au until annealing
      at 600 degrees  C. Nevertheless, both TiN and TiON may be better suited than Au
      or SRO for high temperature applications operating under vacuum conditions.

PMID- 30114831
TI  - Chirp-control of resonant high-order harmonic generation in indium ablation
      plumes driven by intense few-cycle laser pulses.
AB  - We have studied high-order harmonic generation (HHG) in an indium ablation plume
      driven by intense few-cycle laser pulses centered at 775 nm as a function of the
      frequency chirp of the laser pulse. We found experimentally that resonant
      emission lines between 19.7 eV and 22.3 eV (close to the 13th and 15th harmonic
      of the laser) exhibit a strong, asymmetric chirp dependence, with pronounced
      intensity modulations. The chirp dependence is reproduced by our numerical time
      dependent Schrodinger equation simulations of a resonant HHG by the model indium
      ion. As demonstrated with our separate simulations of HHG within the strong field
      approximation, the resonance can be understood in terms of the chirp-dependent
      HHG photon energy coinciding with the energy of an autoionizing state to ground
      state transition with high oscillator strength. This supports the validity of the
      general theory of resonant four-step HHG in the few-cycle limit.

PMID- 30114832
TI  - Three-dimensional super-resolution correlation-differential confocal microscopy
      with nanometer axial focusing accuracy.
AB  - We present a correlation-differential confocal microscopy (CDCM), a novel method
      that can simultaneously improve the three-dimensional spatial resolution and
      axial focusing accuracy of confocal microscopy (CM). CDCM divides the CM imaging
      light path into two paths, where the detectors are before and after the focus
      with an equal axial offset in opposite directions. Then, the light intensity
      signals received from the two paths are processed by the correlation product and
      differential subtraction to improve the CM spatial resolution and axial focusing
      accuracy, respectively. Theoretical analyses and preliminary experiments indicate
      that, for the excitation wavelength of lambda = 405 nm, numerical aperture of NA
      = 0.95, and the normalized axial offset of uM = 5.21, the CDCM resolution is
      improved by more than 20% and more than 30% in the lateral and axial directions,
      respectively, compared with that of the CM. Also, the axial focusing resolution
      important for the imaging of sample surface profiles is improved to 1 nm.

PMID- 30114833
TI  - Chasing quantitative biases in neutron imaging with scintillator-camera
      detectors: a practical method with black body grids.
AB  - We propose a method for improving the quantification of neutron imaging
      measurements with scintillator-camera based detectors by correcting for
      systematic biases introduced by scattered neutrons and other sources such as
      light reflections in the detector system. This method is fully experimental,
      using reference measurements with a grid of small black bodies (BB) to measure
      the bias contributions directly. Using two test samples, one made of lead alloy
      and having a moderate (20%) neutron transmission and one made of stainless-steel
      and having a very low (1%) transmission, we evaluated the improvement brought by
      this method in reducing both the average quantification bias and the uncertainty
      around this average bias after tomographic reconstruction. The results show that
      a reduction of the quantification bias of up to one order of magnitude can be
      obtained. For moderately transparent samples, little sensitivity is observed to
      the parameters used for the correction. For the more challenging sample with very
      low transmission, a correct placement of the BB grid is of utmost importance for
      a successful correction.

PMID- 30114834
TI  - Investigation on 1.3 MUm laser performance with Nd:Gd0.69Y0.3TaO4 and
      Nd:Gd0.68Y0.3NbO4 mixed crystals.
AB  - Laser performances around 1.3 MUm are investigated in 879 nm laser diode (LD) end
      pumped Nd3+ doped mixed crystals with Nd:Gd0.69Y0.3TaO4 and Nd:Gd0.68Y0.3NbO4
      crystals for the first time to our best knowledge. The maximum average power in
      LD end pumped Nd:Gd0.69Y0.3TaO4 1328 nm laser reaches 435 mW at 50 Hz with an
      optical-to-optical efficiency of 5.0% and a slope efficiency of 6.9%. In
      comparison, the highest average power of LD end pumped Nd:Gd0.68Y0.3NbO4 laser at
      1337 nm is 190 mW at 50 Hz, corresponding to an optical-to-optical efficiency of
      3.5% and a slope efficiency of 4.2%.

PMID- 30114835
TI  - Theoretical analysis of the SRS-induced mode distortion in large-mode area fiber
      amplifiers.
AB  - In this paper, the spectral evolution properties of different transverse modes
      with the stimulated Raman scattering (SRS) effect are analyzed in large-mode-area
      (LMA) fiber amplifiers for the first time. Both the ratios of laser power in
      Raman Stokes light and high order modes (HOMs) can be calculated through the
      comprehensive analysis of transverse mode competition and nonlinear transverse
      mode coupling processes. The theoretical study reveals that SRS-induced inter
      modal wave mixing (IM-WM) effect would transfer power from signal light in LP01
      mode to Raman Stokes light in LP11 mode and lead to the onset of the mode
      distortion phenomenon in high-power LMA fiber amplifiers. Different from the
      traditional thermal-induced mode instability (MI) phenomenon, the SRS-induced
      mode distortion could occur by just with the contribution of quantum noise.

PMID- 30114836
TI  - Suppression of inter-modal four-wave mixing in high-power fiber lasers.
AB  - For the inter-modal four-wave mixing (IMFWM) in high-power fiber lasers, the
      phase-matching frequency shift and coherence length are calculated to determine
      the fiber mode combinations corresponding to IMFWM peaks; then, the parameters of
      the laser are optimized accordingly to suppress the IMFWM. On the basis of laser
      parameter optimization, the fiber coiling method is applied to further suppress
      the IMFWM. To validate this method, a master oscillator power amplifier was
      configured with 20/400 fiber to produce IMFWM peaks at 1108 and 1071.6 nm in the
      output spectrum, and then those peaks were removed by reducing the bending radius
      of the fiber.

PMID- 30114837
TI  - Hybrid low-permittivity slot-rib plasmonic waveguide based on monolayer two
      dimensional transition metal dichalcogenide with ultra-high energy confinement.
AB  - A hybrid plasmonic waveguide design is proposed that incorporates a two
      dimensional transition metal dichalcogenide monolayer covered slot-rib in between
      a cylindrical waveguide and a metal surface. A deep optical energy confinement
      (mode area ranging from lambda2/1000000-lambda2/100000) along with a reasonable
      propagation length (5MUm-25MUm) can be realized at the working wavelength of 1550
      nm. In comparison with a traditional hybrid plasmonic waveguide, the proposed
      waveguide structure exhibits a smaller mode area as well as a higher figure of
      merit. Investigation on the influence of various two-dimensional materials on
      modal properties reveals that a larger permittivity provides a stronger field
      confinement. Owing to its excellent energy field confinement with low
      transmission loss, the proposed waveguide can be utilized in a variety of
      plasmonic devices such as compact plasmonic chips, high-integration plasmonic
      nano-lasers and high-sensitivity plasmonic detectors.

PMID- 30114838
TI  - Depth extraction with offset pixels.
AB  - Numerous depth extraction techniques have been proposed in the past. However, the
      utility of these techniques is limited as they typically require multiple imaging
      units, bulky platforms for computation, cannot achieve high speed and are
      computationally expensive. To counter the above challenges, a sensor with Offset
      Pixel Apertures (OPA) has been recently proposed. However, a working system for
      depth extraction with the OPA sensor has not been discussed. In this paper, we
      propose the first such system for depth extraction using the OPA sensor. We also
      propose a dedicated hardware implementation for the proposed system, named as the
      Depth Map Processor (DMP). The DMP can provide depth at 30 frames per second at
      1920 * 1080 resolution with 31 disparity levels. Furthermore, the proposed DMP
      has low power consumption as for the aforementioned speed and resolution it only
      requires 290.76 mW. The proposed system makes it an ideal choice for depth
      extraction systems in constrained environments.

PMID- 30114839
TI  - Discrimination of viable and dead microbial materials with Fourier transform
      infrared spectroscopy in 3-5 micrometers.
AB  - We present a method to show that average mass extinction coefficient of microbes
      evaluated via Lorenz-Mie theory can be used to discriminate between viable and
      dead microbes. Reflectance of viable and dead self-cultured fungal spores and
      mycelia were measured by the Fourier transform infrared spectroscopy. Complex
      refractive indices and mass extinction coefficient of viable and dead fungal
      spores and mycelia were obtained in terms of Kramers-Kronig (KK) relation and
      Lorenz-Mie theory respectively. Smoke box experimental system was built to
      validate the effectiveness of the method. The results show that viable and dead
      fungal spores and mycelia via average mass extinction coefficients can be
      distinguished. The method can be used to discriminate the bioactivity of microbes
      and has potential applications in identification, detection, and optical
      characteristics of viable and dead microbial materials.

PMID- 30114840
TI  - Evaluation of structural and molecular variation of starch granules during the
      gelatinization process by using the rapid Mueller matrix imaging polarimetry
      system.
AB  - Starch is an essential and widely distributed natural material, but its detailed
      conformation and thermal transition properties are not yet well understood. We
      present a rapid Mueller matrix imaging system to explore the structural
      characteristics of starch granules by using 16 measurements with different
      incoming and outgoing polarizations. Due to the minimum rotation of the optical
      elements and the self-calibration ability of this system, the full Mueller matrix
      images can be accurately obtained within ten-odd seconds. Both structural and
      molecular features of the starch granule were investigated in the static state
      and gelatinization process by means of multiple optical characteristics deduced
      from the Mueller matrix. The experimental results for the structural changes
      during the gelatinization were close to other nonlinear optical approaches;
      moreover, the crystallinity and optical rotation of the starch granule are also
      determined through the use of this approach.

PMID- 30114842
TI  - Direct detection of polarization multiplexed single sideband signals with
      orthogonal offset carriers.
AB  - We propose a novel direct detection (DD) scheme for polarization division
      multiplexed (PDM) single sideband (SSB) signals with two orthogonal carriers
      located at the opposite sides. Polarization diversity is realized with a pair of
      optical filters that are used to suppress the unwanted orthogonal carrier
      component. A PDM-SSB DD receiver is thus constructed without polarization de
      rotation. The intra-polarization signal-signal beat interference (SSBI) can be
      mitigated by Kramers-Kronig detection or iterative SSBI cancellation. For inter
      polarization SSBI mitigation, we propose a joint iterative SSBI cancellation
      method. The proposed PDM-SSB DD scheme is validated with a principle experiment
      of 40Gbaud PDM-SSB 16-ary quadrature amplitude modulation (16-QAM) signals. After
      80km standard single-mode fiber (SSMF) transmission, the bit-error rates (BERs)
      achieve 20% hard-decision forward error correction (HD-FEC) threshold of 1.5 * 10
      2. The performance of iterative SSBI cancellation, Kramers-Kronig detection, and
      joint iterative SSBI cancellation are evaluated for PDM-SSB signals with
      different carrier-to-signal ratios (CSPRs) through numerical simulations.
      Moreover, a multi-input-multi-output (MIMO) equalization scheme is proposed and
      validated with numerical simulation, which can suppress the linear inter
      polarization crosstalk and relax the sharpness requirement of optical filter
      edges.

PMID- 30114841
TI  - Visualized charge transfer processes in monolayer composition-graded WS2xSe2(1-x)
      lateral heterojunctions via ultrafast microscopy mapping.
AB  - Two-dimensional transitional metal dichalcogenides (TMDCs) based lateral
      heterojunctions have emerged as appealing and intriguing materials for
      applications in the next generation flexible nanoelectronics. The construction of
      depletion region near the in-plane interface brings rich opto-electrical
      dynamics, which is essential for future applications. Due to the synchronous
      requirement of spatial and time resolution, the study of lateral heterojunction
      dynamics remains a challenging issue. Herein, with a home-built spatiotemporal
      femtosecond transient absorption (TAS) spectroscopy platform, we have
      investigated the ultrafast photocarrier dynamics of monolayer spatial composition
      graded WS2xSe2(1-x) lateral heterojunctions. At the alloy interface, the charge
      transfer (CT) processes have been visualized and referred to occur in 1 ps time
      scale. The mobility difference between electrons and holes results in the space
      modulation of the interface and a significant broadening of rising edge on the
      shell region. Moreover, carrier lifetime near the interface is extraordinarily
      extended by over 3 times from 153 ps to 678 ps. All these results unveil its
      great potential in designing future low cost logic devices and ultrafast optical
      applications.

PMID- 30114843
TI  - Light emitting properties of Si+ self-ion implanted silicon-on-insulator from
      visible to infrared band.
AB  - The photoluminescence (PL) properties of silicon-on-insulator (SOI) samples,
      modified by the Si+ self-ion-implantation (SII) into Si thin film followed by
      annealing, have been well investigated. The well-known W-line can also be
      observed in SII SOI samples, its emitting behavior and structural evolution have
      been discussed in this article. The parallel PL pattern trend and the similar
      changes of temperature-dependent intensity suggest that luminescence center of I1
      and I2 peaks located in the near-infrared band originates from the same
      interstitial-clusters (InCs). The PL peak at 1.762 eV can be ascribed to the
      quantum confinement (QC) from small-sized Si nanocrystals. Based on the electron
      spin resonance (ESR) experiments and the variation of normalized PL intensities
      at different annealing temperature (TA), the neutral oxygen vacancy (NOV) [O3=Si
      Si=O3] is proposed to be responsible for the blue emission of P2 and P3 peaks,
      whose intensity can be restrained by the existence of the paramagnetic E1'
      defects [O3=Si+]. The density of E1' defect is found to reduce with the increase
      of annealing temperature (TA). Our results provide a useful method to identify
      the origin of luminescence centers and pave a way for the application of new type
      optical defects on silicon based light emitting devices (LEDs).

PMID- 30114844
TI  - Post-fabrication trimming of photonic crystal nanobeam cavities by electron beam
      irradiation.
AB  - We demonstrate that resonant wavelength of photonic crystal (PhC) nanobeam
      cavities can be individually post-fabrication tuned by electron beam irradiation.
      By measuring the transmission spectrum of the cavities before and after trimming,
      it is shown that resonant wavelength shifts are proportional to the scanning time
      and the acceleration voltage. Furthermore, larger resonant wavelength shifts can
      be achieved by scanning the region where the electric field is highly localized.
      The measurement results show that the resonant wavelength difference can be
      reduced from 5.5 nm (before trimming) to 0.4 nm (after trimming), while the
      quality factor of the cavities can be maintained.

PMID- 30114845
TI  - Mode selective up-conversion detection for LIDAR applications.
AB  - We study mode selective up-conversion detection as a viable approach to improving
      signal-to-noise and ranging resolution in LIDAR applications. It involves pumping
      a nonlinear waveguide at the edge of phase matching with picosecond pulses, so
      that only the backscattered signal photons in a single or few desirable time
      frequency modes are efficiently up-converted while the broadband background noise
      in all other modes is rejected. We demonstrate a 41-dB increase in the signal-to
      noise ratio for single-photon counting compared to that of direct detection using
      a commercial InGaAs single-photon detector, while achieving sub-millimeter
      ranging resolution with few detected photons. The proposed technique implies new
      LIDAR capabilities for ranging and imaging.

PMID- 30114846
TI  - Theoretical ranging performance model and range walk error correction for photon
      counting lidars with multiple detectors.
AB  - Ranging performance is the key indicator for a ranging lidar system, and a
      theoretical ranging performance model can be used for optimizing systematic
      parameters when designing a lidar system. The fluctuation of the signal photon
      numbers introduces range walk error to photon-counting lidars that can be as high
      as tens of centimeters. In this paper, based on the lidar equation and the
      statistical property of photon-counting detectors, a theoretical ranging
      performance model for photon-counting lidars with multiple detectors is first
      derived. Next, a theoretical correction method for offsetting range walk error is
      proposed, as verified by experiments using a Gm-APD (Geiger mode avalanche
      photodiode) lidar system. The results indicate that multiple detectors are very
      useful to maintain a consistent ranging precision when the mean received signal
      photons are variable. With a 1600 repetitive ranging measurement, the new method
      can achieve a centimeter ranging accuracy, with a mean and standard deviation of
      the residual errors of 1.14 cm and 1.23 cm, respectively. This new method is
      potentially suitable for a satellite photon-counting lidar system such as ICESat
      2, as only a certain number of repetitive measurements, the time tag, and a
      certain number of triggered detectors are required to offset the range walk
      error.

PMID- 30114847
TI  - Graphene-based hybrid plasmonic waveguide for highly efficient broadband mid
      infrared propagation and modulation.
AB  - In this paper, a graphene-based hybrid plasmonic waveguide is proposed for highly
      efficient broadband surface plasmon polariton (SPP) propagation and modulation at
      mid-infrared (mid-IR) spectrum. The hybrid plasmonic waveguide is composed of a
      monolayer graphene sheet in the center, a polysilicon gating layer, and two inner
      dielectric buffer layers and two outer parabolic-ridged silicon substrates
      symmetrically placed on both sides of the graphene. Owing to the unique parabolic
      ridged waveguide structure, the light-graphene interaction and subwavelength SPPs
      confinement of the fundamental SPP mode for the hybrid waveguide can be
      significantly increased. Under the graphene chemical potential of 1.0 eV, the
      proposed waveguide can achieve outstanding SPP propagation performance with long
      propagation length of 12.1-16.7 MUm and small normalized mode area of ~10-4 in
      the frequency range of 10-20 THz, exhibiting more than one order smaller in the
      normalized mode area while remaining the propagation length almost the same level
      with respect to the hybrid plasmonic waveguide without parabolic ridges. By
      tuning the graphene chemical potential from 0.1 to 1.0 eV, we demonstrate the
      waveguide has a modulation depth greater than 51% for the frequency ranging from
      10 to 20 THz and reaches a maximum of nearly 100% at the frequency higher than 18
      THz. Benefitting from the excellent broadband mid-IR propagation and modulation
      performance, the graphene-based hybrid plasmonic waveguide may open up a new way
      for various mid-IR waveguides, modulators, interconnects and optoelectronic
      devices.

PMID- 30114848
TI  - Snapshot multispectral polarization imaging using a photonic crystal filter
      array.
AB  - A new filter array and a demosaicking method for snapshot multispectral
      polarization imaging are proposed in this paper. The proposed filter array is a
      thin-film wavy multilayer structure regarded as a photonic crystal that can be
      fabricated using the autocloning method. The multispectral polarization filter
      array is developed by altering the wave structure of the photonic crystal at each
      pixel. In addition, we propose a demosaicking method for multispectral
      polarization images by considering snapshot imaging as a linear model. In the
      experiments, we evaluated the recovered spectrum error in some color charts and
      showed various demosaicked images such as multispectral polarization images,
      specific-band degree of linear polarization images, polarized RGB images, and non
      polarized RGB images.

PMID- 30114849
TI  - Laser-induced plasma imaging for low-pressure detection.
AB  - A novel technique based on laser induced plasma imaging is proposed to measure
      residual pressure in sealed containers with transparent walls, e.g. high voltage
      vacuum interrupter in this paper. The images of plasma plumes induced on a copper
      target at pressure of ambient air between 10-2Pa and 105Pa were acquired at delay
      times of 200ns, 400ns, 600ns and 800ns. All the plasma images at specific
      pressures and delay times showed a good repeatability. It was found that ambient
      gas pressure significantly affects plasma shape, plasma integral intensities and
      expansion dynamics. A subsection characteristic method was proposed to extract
      pressure values from plasma images. The method employed three metrics for
      identification of high, intermediate and low pressures: the distance between the
      target and plume center, the integral intensity of the plume, and the lateral
      size of the plume, correspondingly. The accuracy of the method was estimated to
      be within 15% of nominal values in the entire pressure range between 10-2Pa and
      105Pa. The pressure values can be easily extracted from plasma images in the
      whole pressure range, thus making laser induced plasma imaging a promising
      technique for gauge-free pressure detection.

PMID- 30114850
TI  - Nanophotonics with 2D transition metal dichalcogenides [Invited].
AB  - Two-dimensional semiconducting transition metal dichalcogenides (TMDCs) have
      recently become attractive materials for several optoelectronic applications,
      such as photodetection, light harvesting, phototransistors, light-emitting
      diodes, and lasers. Their bandgap lies in the visible and near-IR range, and they
      possess strong excitonic resonances, high oscillator strengths, and valley
      selective response. Coupling these materials to optical nanocavities enhances the
      quantum yield of exciton emission, enabling advanced quantum optics and
      nanophotonics devices. Here, we review the state-of-the-art advances of hybrid
      exciton-polariton structures based on monolayer TMDCs coupled to plasmonic and
      dielectric nanocavities. We discuss the optical properties of 2D WS2, WSe2, MoS2
      and MoSe2 materials, paying special attention to their energy bands,
      photoluminescence/absorption spectra, excitonic fine structure, and to the
      dynamics of exciton formation and valley depolarization. We also discuss light
      matter interactions in such hybrid exciton-polariton structures. Finally, we
      focus on weak and strong coupling regimes in monolayer TMDCs-based exciton
      polariton systems, envisioning research directions and future opportunities for
      this material platform.

PMID- 30114851
TI  - Nanophotonic control of thermal radiation for energy applications [Invited].
AB  - The ability to control thermal radiation is of fundamental importance for a wide
      range of applications. Nanophotonic structures, where at least one of the
      structural features are at a wavelength or sub-wavelength scale, can have thermal
      radiation properties that are drastically different from conventional thermal
      emitters, and offer exciting opportunities for energy applications. Here we
      review recent developments of nanophotonic control of thermal radiation, and
      highlight some exciting energy application opportunities, such as daytime
      radiative cooling, thermal textile, and thermophotovoltaic systems that are
      enabled by nanophotonic structures.

PMID- 30114852
TI  - Photonic switching in high performance datacenters [Invited].
AB  - Photonic switches are increasingly considered for insertion in high performance
      datacenter architectures to meet the growing performance demands of
      interconnection networks. We provide an overview of photonic switching
      technologies and develop an evaluation methodology for assessing their potential
      impact on datacenter performance. We begin with a review of three categories of
      optical switches, namely, free-space switches, III-V integrated switches and
      silicon integrated switches. The state-of-the-art of MEMS, LCOS, SOA, MZI and MRR
      switching technologies are covered, together with insights on their performance
      limitations and scalability considerations. The performance metrics that are
      required for optical switches to truly emerge in datacenters are discussed and
      summarized, with special focus on the switching time, cost, power consumption,
      scalability and optical power penalty. Furthermore, the Pareto front of the
      switch metric space is analyzed. Finally, we propose a hybrid integrated switch
      fabric design using the III-V/Si wafer bonding technique and investigate its
      potential impact on realizing reduced cost and power penalty.

PMID- 30114853
TI  - Eleanor H. Slifer: An appreciation.

PMID- 30114854
TI  - Establishment of the site of involution at novel locations on the amphibian
      embryo.
AB  - Anuran (Rana) and urodele (Ambystoma) amphibian eggs were subjected to prolonged
      unnatural orientations in relation to gravity. In some cases eggs were rotated 90
      degrees , while in other instances eggs were rotated 180 degrees  (complete
      inversion). Alterations in the pigmentation pattern, cleavage pattern, and site
      of involution were observed. Despite these unnatural orientations to gravity, the
      morphogenesis of axial structures was frequently normal. Reorganization of the
      egg cytoplasm apparently takes place after the unnatural orientation. Rather than
      being localized in a fixed position in the egg (e.g., the egg cortex), the
      determinants for the pattern of early embryogenesis are probably located in that
      portion of the cytoplasm (e.g., "internal" cytoplasm) that orients to gravity.

PMID- 30114855
TI  - Evidence for the holocrine nature of lipoid secretion by avian epidermal cells: A
      histochemical and fine structural study of rictus and the uropygial gland.
AB  - Cells of the avian epidermis (rictus of the chicken), when examined under the
      light microscope following suitable fat staining, show similarities to epithelial
      cells of the uropygial gland of chicken and pigeon, an organ which is recognized
      both morphologically and functionally as a holocrine gland. Evidence thus far
      from electron microscopic studies strongly suggests that the skin of the bird is
      also a holocrine gland, although details of cytogenesis and secretion differ
      somewhat in the two organs.

PMID- 30114856
TI  - Development and metamorphosis of the digestive system of larval lobsters, Homarus
      americanus (Decapoda: Nephropidae).
AB  - This study provides a detailed account of the development of the digestive system
      of larval lobsters (Homarus americanus H. Milne Edwards, 1837) and the
      morphological changes that occur at metamorphosis. The most dramatic of these
      changes involves the gastric mill of the cardiac stomach. First-and second-stage
      lobsters lack the medial and lateral teeth characteristic of the grinding stomach
      of adult lobsters. Clearly recognizable, heavily cuticularized teeth first appear
      in the third stage, and accessory lateral teeth do not appear until the fourth
      stage. In place of the teeth of the gastric mill, first- and second-stage
      stomachs have a series of pads and ridges which are the apparent rudiments of the
      teeth. The development of the gastric mill during the larval stages enables
      lobsters to deal successfully with the more substantial food they encounter in
      the benthic environment, and corresponds to the drastic change of habitat and
      diet which occurs at metamorphosis. Confusion about the extent of the midgut and
      hindgut in larval lobsters has been clarified. The results of this study have
      shown that the larvae have a long midgut, which lacks a cuticle, and a short
      hindgut with a cuticular lining, just as in adult lobsters. The junction between
      midgut and hindgut lies in the sixth abdominal segment in all of the first four
      stages, as well as in the adult.

PMID- 30114857
TI  - Correlation of cyclic GMP and cyclic AMP immunofluorescence with cytochemical
      patterns during dormancy release and development from gemmules in Spongilla
      lacustris L. (Porifera: Spongillidae).
AB  - The spongillid freshwater sponges asexually produce an encapsulated dormant
      stage, the gemmule. With release from dormancy, internal, yolk-laden, binucleate
      thesocytes differentiate into histoblasts or archeocytes. The histoblasts
      emerging first from the gemmule form the initial pinacoderm of the hatching
      sponge. Immunohistochemistry was employed to examine the distribution of cyclic
      GMP (cGMP) and cyclic AMP (cAMP) following dormancy release and during gemmule
      germination and hatching in the freshwater sponge, Spongilla lacustris L. Cyclic
      nucleotide fluorescence patterns were analyzed in relation to the distribution of
      cytochemically demonstrable macromolecular constituents and intracellular
      organelles. Twenty-four hours following temperature-activated release from
      dormancy, cGMP fluorescence levels are elevated in thesocytes at the gemmule
      periphery prior to histoblast formation. The cAMP fluorescence in the gemmule
      also occurs first in those thesocytes differentiating into histoblasts.
      Cytochemical patterns in germinating gemmules are comparable with those described
      by Ruthmann ('65) and Tessenow ('69). However, cytochemically demonstrable events
      of cytodifferentiation follow the earlier appearance of cGMP and cAMP in the
      histoblast precursors by approximately 12 hours. In addition, cGMP appears to be
      associated with the membranes of cytoplasmic organelles, possibly lysosomes or
      lipid inclusions, in the region of vitelline platelets and with symbiotic algae.
      cAMP is located primarily on the membranes of the vitelline platelets and on
      membranes of vacuoles involved in forming the spicular skeleton These
      observations suggest that cGMP and cAMP are involved in the mobilization of
      nutrient reserves and in ion transport during dormancy release and development
      from gemmules in freshwater sponges.

PMID- 30114858
TI  - Digital morphology in Varanus and Iguana.
AB  - Marked tendinous bands lie along the lateral sides of the fingers in Varanus and
      Iguana and have asymmetrical roots in the metacarpal region. The radial band of
      each finger represents the distal extension of an oblique band arising at an ulno
      dorsally located line in the proximal part of the metacarpal, whereas the ulnar
      bands each form a tendinous extension of an interosseus muscle bundle. The
      function of this metacarpo-digital system must be seen in relation to the
      deformations of the hand, imposed during locomotion by longitudinal rotation of
      the forearm. The latter motion results from the foreward and backward sway of the
      humerus with the elbow bent at 90 degrees .

PMID- 30114859
TI  - Determination of temperature sensitive stages for sexual differentiation of the
      gonads in embryos of the turtle, Emys orbicularis.
AB  - In order to determine the temperature sensitive stages for sexual differentiation
      of the gonads in Emys orbicularis, eggs of this turtle were shifted at different
      stages of embryonic development from the male-producing temperature of 25 degrees
      C to the female-producing temperature of 30 degrees C and reciprocally. Based on
      the series of developmental stages described by Yntema ('68) for Chelydra
      serpentina, temperature begins to influence sexual differentiation of Emys
      orbicularis at stage 16, a stage in which the gonads are still histologically
      undifferentiated. Its action lasts over the first steps of histological
      differentiation of the gonads. The minimal exposure at 25 degrees C required for
      male differentiation of all individuals extends from stage 16 to somewhat before
      stage 21. For 100% female differentiation, incubation at 30 degrees C must be
      longer, from stage 16 to somewhat before stage 22. Shorter exposures at 25
      degrees C or 30 degrees C during these periods result in different percentages of
      males, females, and intersexes. Our results show that there is a critical stage
      (stage 16) which is the same for both male and female differentiation of the
      gonads. The thermosensensitive periods are rather long, corresponding to 11-12
      days at 25 degrees C and 30 degrees C.

PMID- 30114860
TI  - Descriptive and functional anatomy of the digital vascular system of the tokay,
      Gekko gecko.
AB  - The vascular system of the digits of the tokay is more complex than has hitherto
      been suspected and has a configuration which suggests it is intimately involved
      in the process of adhesion. Distinction can be made between lamellae (expanded
      scales beneath the proximal portion of the digit) and scansors (elaborations of
      lamellae that contain a large amount of subdermal material and therefore do not
      technically qualify as scales). Such a distinction is made on anatomical grounds
      and can be appreciated only if anatomical investigation is carried out. There are
      no externally obvious features by which lamellae and scansors can be
      distinguished, except position. Scansors are found beneath hyperextensible
      phalanges, whereas lamellae are located more proximally and are not subjected to
      digital hyperextension during locomotion. Whether this distinction can be applied
      to other pad-bearing geckos and to anoline lizards remains to be seen. The large
      sinus beneath the penultimate phalanx appears to govern the pressure within the
      system; the reticular blood systems of the scansors appear to manifest the
      pressure changes with respect to the locomotor substratum. Changes in pressure
      within the system probably permit the overlapping scansors to comply precisely
      with each other and with the substratum. The presence of a system based on fluid
      pressure differentials means that scansors are deformable along multiple axes at
      any one time, thus permitting a high degree of compliance with their entire
      surroundings. It is probable that changes in pressure within the system promote
      release from the substratum as well as compliance with and attachment to it. The
      mechanism of control of the system awaits further investigation. The pattern of
      the digital vascular complex has been considered in relation to the mode of
      operation of the digits during locomotion. Distal drainage of the sinus is
      ideally suited to the activity of hyperextension of the digits. This combination
      permits sequential pressurizing and depressurizing of the scansors and allows the
      bond to be created or broken in a gradual fashion rather than in an all-or-none
      manner. By avoiding sudden shifts in the pattern of dynamic loading (the bond is
      not broken instantaneously but sequentially), the risk of transverse instability
      during locomotion is lessened. The increase of loading on the other feet is thus
      gradual. The importance of this is discussed more fully elsewhere in a
      consideration of the structure and function of scansors. That the digits of the
      tokay are hyperextended during horizontal as well as vertical locomotion
      (Russell, '75, p. 463) can now be rationalized not only from the point of view of
      protection of the setae but also because of the manner in which the vascular
      system of the digits functions and is drained.

PMID- 30114863
TI  - Questions to ask a patient with nocturia.
AB  - BACKGROUND: Patients may not raise nocturia as a concern as they mistakenly
      consider the symptom to be a normal part of ageing. Nocturia is associated with
      significant morbidity and is likely to be a marker of poor health. OBJECTIVE:
      This paper provides questions to guide diagnosis, evaluation and individualised
      treatment of nocturia. DISCUSSION: Nocturia results from the interplay between
      nocturnal polyuria, reduced bladder storage and sleep disruption. Changes in the
      function of the urinary bladder, kidneys, brain and cardiovascular system, and
      hormone status underlie the development and progression of nocturia. Medications
      commonly prescribed to older people can affect development or resolution of
      nocturia. The bother caused to a patient by waking to void relates to disturbance
      of slow-wave sleep, the physical act of getting out of bed and resulting chronic
      fatigue. An assessment process that identifies relevant and co-existing causes of
      an individual's nocturia will facilitate a targeted approach to treatment.

PMID- 30114862
TI  - Differential MicroRNA Expression between EGFR T790M and L858R Mutated Lung
      Cancer.
AB  - BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that mediate post
      transcriptional gene regulation. They are commonly deregulated in human
      malignancies, including non-small cell lung cancer (NSCLC). The aim of this study
      is to investigate miRNA expression in T790M-mutated NSCLC resistant to epidermal
      growth factor receptor (EGFR) tyrosine kinase inhibitors. METHODS: Six cases of
      resected NSCLC harboring the T790M mutation were examined. We performed miRNA
      time polymerase chain reaction (PCR) array profiling using EGFR T790M-mutated
      NSCLC and L858R-mutated NSCLC. Once identified, miRNAs that were differentially
      expressed between the two groups were validated by quantitative real-time
      polymerase chain reaction (qRT-PCR). RESULTS: miRNA PCR array profiling revealed
      three up-regulated miRNAs whose expression levels were altered 4.0-fold or more
      in the EGFR T790M mutation group than in the L858R group: miR-1 (fold change,
      4.384), miR-196a (fold change, 4.138), and miR-124 (fold change, 4.132). The
      three differentially expressed miRNAs were validated by qRT-PCR, and they were
      found to be overexpressed in the T790M group relative to L858R group. In
      particular, expression levels of miR-1 and miR-124 were significantly higher in
      the T790M group (p-value of miR-1 = .004, miR-124 = .007, miR-196a = .096).
      CONCLUSIONS: MiR-1, miR-124, and miR-196a are overexpressed in EGFR T790M mutated
      NSCLC.

PMID- 30114864
TI  - Female pattern hair loss.
AB  - BACKGROUND: Female pattern hair loss (FPHL) is a commonly encountered clinical
      presentation in primary care. Patterned hair loss in women is characterised by
      diffuse hair thinning and often becomes an ongoing cause of psychosocial
      distress. OBJECTIVE: The aim of this article is to present a practical approach
      for the clinical assessment of female hair loss and to review the up-to-date
      treatment modalities. DISCUSSION: Alopecia can be the first symptom of systemic
      illness. It is therefore crucial for the primary care physician to be able to
      differentiate between FPHL and more concerning causes of hair loss. Treatment
      options often involve a combination of non-androgenic and androgenic therapy. The
      use of oral minoxidil in combination with oral spironolactone is a novel therapy
      with promising results. The role of the general practitioner is paramount in
      establishing the diagnosis, setting achievable therapeutic goals and navigating
      the psychosocial comorbidity associated with this chronic condition.

PMID- 30114865
TI  - Review and update of benign prostatic hyperplasia in general practice.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common benign tumour
      in men. Although men with BPH often need medical or surgical management from a
      urologist at some point throughout the timeline of their disease, most men are
      initially assessed and managed by a general practitioner (GP) in the primary
      healthcare setting. OBJECTIVE: The aim of this article is to highlight the
      principles of the pathogenesis, presentation, assessment and management of BPH in
      a primary care setting. DISCUSSION: Between 2009 and 2011, BPH was managed by GPs
      at approximately 228,000 general practice visits per annum in Australia. Several
      changes in pharmaceutical agents and surgical intervention have occurred over the
      past decade. As a result, it is imperative that GPs remain up to date with
      assessment and management of BPH, are aware of new therapies and understand when
      to refer to a urologist.

PMID- 30114866
TI  - A brief review of global climate change and the public health consequences.
AB  - BACKGROUND: Global climate change (GCC) will have an enormous impact on public
      health in the 21st century. Evidence clearly implicates the use of fossil fuels
      and the resultant anthropogenic greenhouse gases as the major source of GCC.
      OBJECTIVE: This paper seeks to examine briefly the association between fossil
      fuels and GCC, the consequent environmental changes and the predicted public
      health effects. DISCUSSION: Complex and interrelated climate changes are forecast
      to present immense challenges, including increased morbidity and mortality,
      arising from heatwaves, extreme weather events, infectious and non-communicable
      diseases. The subsequent health effects, modulated by socioeconomic determinants,
      will be distributed inequitably primarily to vulnerable populations, largely in
      the tropics. A response to GCC is urgently required, involving strategies to
      mitigate and adapt to GCC. Not only will general practitioners be managing health
      conditions caused by GCC, but they are also well placed in the community to
      advocate for GCC mitigation.

PMID- 30114861
TI  - Interleukin-31, Interleukin-31RA, and OSMR Expression Levels in Post-burn
      Hypertrophic Scars.
AB  - BACKGROUND: Although several studies have shown the role of interleukin-31 (IL
      31) and its receptors in inducing pruritus in certain skin disorders, knowledge
      of its role in post-burn hypertrophic scars is insufficient. Therefore, the
      histopathological expression levels of IL-31, IL-31 receptor alpha (IL-31RA), and
      oncostatin M receptor (OSMR) in post-burn hypertrophic scar tissues were
      investigated and compared with normal tissue expression levels. METHODS: Samples
      of hypertrophic scar tissue were obtained from 20 burn patients through punch
      biopsy. Normal samples were obtained from areas adjacent to the burn injury site
      of the same patients. Samples were placed in 10% neutral buffered formalin,
      embedded in paraplast, and processed into serial 5-MUm sections.
      Immunohistochemistry results were semi-quantitatively evaluated for IL-31, IL
      31RA, and OSMR. By hematoxylin and eosin staining, epidermal and dermal thickness
      were assessed with a microscope and digital camera. Intensities were rated on a
      scale of 1 to 4. RESULTS: Percentages for IL-31, IL-31RA, and OSMR in the
      epidermal basal layer cell cytoplasm were significantly greater in the burn scar
      tissue compared to normal skin, as well as the dermal and epidermal thickness (p
      < .05). There was a significant difference in IL-31 epidermal basal layer
      intensity in burn scar tissue compared to normal skin (p < .05). Besides the OSMR
      basal layer intensity, IL-31 and IL-31RA intensities between the burn scar and
      normal tissues were not significant. However, correlations were significant,
      indicating that the greater the infiltration percentage, the higher the intensity
      (p < .05). CONCLUSIONS: IL-31, IL-31RA, and OSMR expression levels are increased
      in hypertrophic scars compared with normal tissue.

PMID- 30114867
TI  - Human papillomavirus vaccination update: Nonavalent vaccine and the two-dose
      schedule.
AB  - BACKGROUND: Australia has included quadrivalent human papillomavirus (HPV)
      vaccination in its national program since 2007. Significant declines have been
      observed in the incidence of HPV infection, genital warts and high-grade cervical
      lesions. In 2018, the program changed to a nonavalent HPV vaccine administered
      over a routine two-dose schedule for the target cohort of adolescents aged 12-13
      years. OBJECTIVE: The aim of this article is to provide an overview of the
      nonavalent HPV vaccine, the rationale for its use and expected outcomes, and to
      review the updated dose scheduling requirements for HPV vaccines. DISCUSSION: The
      nonavalent HPV vaccine will broaden the impact of HPV vaccination, primarily
      against cervical cancer and pre-cancer. A two-dose schedule with an interval of 6
      12 months between doses is appropriate for those aged <=14 years at the time of
      first dose. Older individuals and those who are immunocompromised should continue
      to receive the three-dose schedule at zero, two and six months.

PMID- 30114868
TI  - Preconception care.
AB  - BACKGROUND: Preconception care (PCC) comprises counselling and the provision of
      biomedical, behavioural and social health interventions to optimise the health of
      women and their partners prior to pregnancy and improve health related outcomes
      for themselves and their children. OBJECTIVE: With a focus on women, the aim of
      this paper is to discuss the evidence for PCC, available guidelines and
      strategies to increase primary care access. DISCUSSION: Each year an estimated
      10% of women in Australia become pregnant. There is increasing evidence that
      optimising health in the preconception period is crucial to improving short-term
      and long-term outcomes for mothers and babies. General practitioners can have a
      key role in assisting women to identify modifiable and non-modifiable
      preconception risks and to make informed decisions about planning or avoiding
      pregnancy. The Royal Australian College of General Practitioners Guidelines for
      preventive activities in general practice includes a chapter on preventive
      activities prior to pregnancy, which is a useful resource. The critical first
      step is screening women for their pregnancy intentions by asking a simple
      question that can help facilitate the start of the PCC conversation.

PMID- 30114869
TI  - Human papillomavirus testing as part of the renewed National Cervical Screening
      Program.
AB  - BACKGROUND: On 1 December 2017, Australia moved to a new National Cervical
      Screening Program (NCSP), which uses primary human papillomavirus (HPV) nucleic
      acid testing (NAT) followed by reflex liquid-based cytology for women aged
      between 25 and 74 years. OBJECTIVE: The aim of this article is to provide an
      overview of the different HPV NAT assays that satisfy the requirements for use in
      the renewed NCSP. DISCUSSION: Australia has adopted innovative, evidence-based
      criteria for the inclusion of HPV NAT assays in the renewed NCSP. These include
      the requirements for detection of all 12 designated oncogenic HPV types,
      including separate detection and reporting of HPV 16 and 18; validation against
      reference assays showing sufficient sensitivity and specificity for the detection
      of underlying high-grade cervical disease; reproducibility; and the presence of
      cellularity and inhibition controls. Practitioners can feel assured that HPV NAT
      undertaken as part of the renewed NCSP will produce high-quality results
      irrespective of location or pathology provider.

PMID- 30114870
TI  - Recurrent pregnancy loss: A summary of international evidence-based guidelines
      and practice.
AB  - BACKGROUND: Recurrent pregnancy loss (RPL) is defined as two or more pregnancy
      losses. It affects <5% of couples. There are many proposed causes; however, in a
      significant proportion of cases, the cause is unknown. OBJECTIVE: The aim of this
      paper is to provide a summary of the aetiology, investigations and management of
      RPL, which is based on the three most recent international guidelines on RPL
      (European Society of Human Reproduction and Embryology, 2017; American Society
      for Reproductive Medicine, 2012; and the Royal College of Obstetricians and
      Gynaecologists, 2011). DISCUSSION: Management of RPL should occur in a
      specialised clinic. Appropriate investigations include karyotyping of parents and
      products of conception, two-dimensional/three-dimensional ultrasonography with
      sonohysterography, thyroid function tests, and antibodies and testing for
      acquired thrombophilias. Management options encompass some lifestyle
      modifications for smoking, alcohol, illicit drug use and caffeine consumption.
      Acquired thrombophilias should be treated with unfractionated heparin and low
      dose aspirin.

PMID- 30114871
TI  - Gestational diabetes mellitus: A pragmatic approach to diagnosis and management.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is a common condition with risks
      for mother and baby. Type 2 diabetes mellitus (T2DM) and obesity are occurring
      with increasing frequency, and the incidence of GDM reflects this trend. Further,
      new diagnostic criteria have greatly increased the prevalence of GDM. Potential
      lifelong consequences exist for mother and baby if the condition goes untreated;
      however, adverse maternal and fetal effects can be ameliorated by effective
      pregnancy management. OBJECTIVE: The aim of this article is to provide practical
      advice regarding GDM diagnosis, management and postpartum follow-up for general
      practitioners, who, increasingly, will be involved in GDM care. DISCUSSION:
      Controversy surrounds many aspects of GDM. Recommendations are frequently based
      on consensus. In the context of a deficient evidence base, any recommendations
      are open to debate. However, it is reasonable to suggest a pragmatic way forward,
      maintaining an open mind about the current diversity of practice and a
      preparedness to include further research findings into future practice.

PMID- 30114872
TI  - Pelvic girdle pain in pregnancy.
AB  - BACKGROUND: Pelvic girdle pain (PGP) in pregnancy is a common condition that can
      cause significant physical disability and has an important psychosocial impact on
      pregnant women and their families. It is often under-reported and poorly managed
      by obstetric caregivers, and this can result in poorer outcomes, reduced quality
      of life and chronic pain. OBJECTIVE: The objective of this article is to discuss
      the practical assessment and management of PGP in pregnancy. DISCUSSION:
      Conservative management that includes activity modification, pelvic support
      garments, management of acute exacerbations, physiotherapy and exercise programs
      can alleviate symptoms and prevent progression of symptoms. General practitioners
      are an integral part of the multidisciplinary team to help manage PGP.

PMID- 30114873
TI  - Intentional self-inflicted and peer-inflicted aerosol skin injuries called
      'frosties': Cohort series and systematic literature review.
AB  - BACKGROUND AND OBJECTIVES: 'Frosties' are deliberate cold skin burns caused by an
      aerosol device. The aim of this article was to examine our own cohort, and those
      previously published, to identify the key features of patients presenting with
      frosties and inform appropriate early clinical interventions. METHOD: We compared
      cases in our dataset that occurred between 1 January 2013 and 30 June 2017 with
      those reported in the literature, focusing on seven domains: sex, age at injury,
      days to presentation, first aid, depth of injury and outcome. RESULTS: The median
      patient age was 13 years; 70.5% were female. Adequate first aid was not reported
      in any patient. Where recorded, the median time to presentation to a health
      service was six days. Where severity of injury was recorded, 13 of 37 cases
      (35.1%) were full thickness, and 10 patients received a split thickness skin
      graft. Two subgroups were identified: cluster injuries and psychological
      distress. DISCUSSION: Cluster injuries occur as the result of a mutual 'test of
      courage'. Solo injuries may point to underlying psychological distress. Frosties
      frequently result in significant burn injuries and often require skin grafting.
      The severity of frosties is underappreciated and, as a consequence, treatment,
      through first aid or presentation to a health service, is delayed or absent.
      General practitioners should be familiar with the appearance of frosties in order
      to identify them in unrelated consultations.

PMID- 30114874
TI  - Management of sore throat in primary care.
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to examine the knowledge,
      attitudes and practices of general practitioners (GPs) in Victoria, Australia in
      the management of sore throat. METHOD: We conducted a cross-sectional survey of
      100 GPs using a questionnaire with the same four case vignettes used in a 1994
      Victorian study. RESULTS: Eighty-nine per cent of respondents indicated they
      would prescribe antibiotics to a child with a short history of sore throat and
      fever, with examination findings of fever, tonsillar pus and tender cervical
      lymph nodes. Only 18% of respondents indicated they would order a throat swab
      with culture to investigate the aetiology. Very few respondents indicated they
      would prescribe antibiotics to patients presenting with sore throat with clinical
      features consistent with a viral infection. DISCUSSION: This study suggests that
      there is a role for better communication of the gradual but practical changes of
      Australian sore throat management guidelines to GPs, which may reduce antibiotic
      prescribing.

PMID- 30114875
TI  - Bringing futurism into medical education: Harnessing augmented reality to foster
      more engagement.

PMID- 30114877
TI  - Women's health.

PMID- 30114876
TI  - Fertility and pregnancy care.

PMID- 30114878
TI  - A new era in cervical cancer prevention.

PMID- 30114881
TI  - A woman with persistent fever and a skin lesion.

PMID- 30114879
TI  - July correspondence.

PMID- 30114882
TI  - Multiple myeloma: Updated approach to management in 2018.
AB  - BACKGROUND: Multiple myeloma is an uncommon haematological cancer of plasma
      cells. Improvements in understanding of this disease have lead to drastic changes
      regarding diagnosis, management and its prognosis. OBJECTIVE: The aim of this
      article is to provide a concise update regarding the current management of
      myeloma in Australia, and important management issues for general practitioners.
      DISCUSSION: With the advent of new treatments, the outcomes of myeloma have
      changed drastically in the past decade, and it is now a disease that requires
      long-term monitoring by both haematologists and general practitioners.

PMID- 30114884
TI  - Denosumab-related hypocalcaemia in chronic kidney disease.

PMID- 30114883
TI  - A general practitioner primer on groin hernias.
AB  - BACKGROUND: Patients, particularly adult males, commonly present to general
      practice with groin hernias. Although rarely life-threatening, groin hernias can
      be associated with considerable morbidity and limitation of earning capacity.
      General practitioners should be equipped with a sound knowledge of the relevant
      anatomy, clinical findings and management principles in order to facilitate all
      aspects of the patient journey. OBJECTIVE: Drawing on evidence from the
      literature and personal clinical experience, this article seeks to enhance
      understanding of groin hernias and provide information on what is considered
      current best practice. DISCUSSION: A number of key points have been generated
      that will serve to inform the management of patients with groin hernias in the
      primary care setting.

PMID- 30114885
TI  - Building a fit-for-purpose Australian primary healthcare workforce.

PMID- 30114886
TI  - Workforce innovation: Embracing emerging technologies.
AB  - BACKGROUND: In a rapidly evolving digital world, it is crucial that general
      practice embraces the potential of artificial intelligence (AI) and virtual
      reality (VR) in a real and proactive manner. OBJECTIVE: Using examples of AI and
      VR, the article outlines some of the benefits and challenges we face in
      integrating these digital tools into daily clinical practice and our training
      programs. DISCUSSION: It is clear that AI and VR digital innovations will
      continue to grow in significance, with more and more options being offered to
      clinicians. As we increase our understanding of the benefits of these
      technologies, adapting our traditional curricula and daily clinical practice will
      require an openness to change. This is somewhat easier with VR, as it is a low
      risk intervention that is providing an additional clinical intervention modality.
      AI is generating more challenges that will require a balanced, ongoing discussion
      involving clinicians and AI practitioners.

PMID- 30114887
TI  - Workforce planning: How we think about the impact of organisations on outcomes.
AB  - BACKGROUND: Healthcare workforce availability and planning is of fundamental
      importance to patients, clinicians, operational managers and strategic leaders
      alike. Despite much attention and development of plans and policy, a definitive
      answer remains elusive. OBJECTIVE: The aim of this article is to encourage
      colleagues to make explicit their underlying assumed models when undertaking
      workforce planning. DISCUSSION: It is posited that, akin to making a holistic
      diagnosis in medicine, understanding workforce issues by uncovering the prisms of
      presupposition and assumption that we hold about organisations is critical to
      generating fruitful new insights. Morgan's organisational metaphors are described
      as one example of a management conceptual model that might help us to illuminate
      these prisms. Examples are given of how each metaphor alters the way in which we
      might address our workforce needs and priorities.

PMID- 30114888
TI  - Developing a general practice workforce for the future.
AB  - BACKGROUND: Australia continues to develop as a multicultural nation, with a
      population that is ageing and developing complex health needs. The world around
      us is changing, and the pace of change is increasing. These contextual changes
      pose challenges for general practice training. OBJECTIVE: This paper explores the
      potential impact of these changes on the general practice workforce. DISCUSSION:
      General practitioners (GPs) will continue to have a central role in coordinating
      continuous, comprehensive care but are more likely to act as managers of multi
      source, continuous monitoring data that facilitate personalised medical care. GPs
      will need to adapt rapidly to change, seizing opportunities offered by disruptive
      technology in a globalised world affected by climate change. The nature and
      impact of change is difficult to predict, and more research is needed to explore
      how change will affect healthcare and healthcare professionals. Ideally, training
      for general practice should include preparation for managing continuous change.

PMID- 30114889
TI  - Producing a general practice workforce: Let's count what counts.
AB  - BACKGROUND: Medical workforce problems still dominate headlines despite
      considerable investment in education, training and other initiatives. There is
      little consensus about what Australia's general practice workforce should look
      like or what training outcomes should be reported. OBJECTIVE: The aim of this
      paper was to explore a number of issues relevant to outcomes of workforce
      programs and offer suggestions for identifying and overcoming these issues.
      DISCUSSION: Social accountability literature highlights the importance of
      outcomes focusing on community needs. We suggest that evaluations should 'count
      what counts' and be careful what is counted. Numbers are only part of the story;
      not everything that counts is counted, and synergies and cooperation are key.
      Australia has many general practice workforce programs that are generally heading
      in the right direction. We believe that closer attention to appropriate outcome
      measures is important if we are to maximise return on investment and get the best
      outcomes for the community.

PMID- 30114890
TI  - General practice work and workforce: Interdependencies between demand, supply and
      quality.
AB  - BACKGROUND: General practice is regarded as central to the Australian health
      system. However, issues affecting the general practitioner (GP) workforce have
      been focused mainly on remuneration, numbers and distribution. The focus is
      shifting to how best to enable GPs to deliver effective, efficient and equitable
      care. OBJECTIVE: The aim of this paper is to identify important elements,
      dynamics and interdependencies that influence GPs' work and their ability to
      continually improve outcomes for individuals and communities. DISCUSSION: Most
      important problems are multifaceted and cannot be reduced to a simple, single
      solution. Influence diagrams capture the interdependent domains that affect
      general practice, such as the variations in patients' needs in the community and
      the impact of disadvantage and care expectations on outcomes. Identifying
      interrelationships between key domains should capture the dynamics that 'feed the
      problem'. Finding 'best possible solutions' to improve interdependent system
      problems and avoid the inherent risk of unintended failures requires an ongoing
      mix of qualitative and quantitative modelling.

PMID- 30114891
TI  - Talking to migrant and refugee young people about sexual health in general
      practice.
AB  - BACKGROUND AND OBJECTIVES: Young people are an important group to target with
      health promotion and preventive healthcare. This paper focuses on the engagement
      of migrant and refugee young people with sexual and reproductive healthcare in
      general practice. METHOD: Semi-structured first interviews (n = 27; 16 female, 11
      male) and follow-up interviews (n = nine; six female, three male) were undertaken
      with migrant and refugee young people aged 16-24 years living in Sydney. RESULTS:
      The majority of participants had seen a general practitioner (GP) for general
      health issues. However, most were reluctant to discuss sexual health with a
      practitioner whom they described as their 'family doctor', primarily because of
      concerns about judgement and confidentiality. Most described negative experiences
      with GPs for sexual health matters, including not being listened to or being
      rushed through the appointment. DISCUSSION: There appears to be a lack of
      effective engagement with migrant and refugee young people by GPs in relation to
      sexual health. Building the skills and confidence of GPs to work with this group
      and promote sexual health and wellbeing should be considered, and efforts should
      be made to communicate confidentiality and trustworthiness.

PMID- 30114892
TI  - What can pharmacists do in general practice? A pilot trial.
AB  - BACKGROUND AND OBJECTIVES: Non-dispensing pharmacists are being suggested as a
      useful addition to the workforce in general practice. The aim of this study was
      to describe the activities of three general practice pharmacists over six months
      in a pilot trial. METHOD: Three general practices integrated a part-time (15.2-16
      hours per week) non-dispensing pharmacist to be employed according to their
      individual skillset and local workplace needs. Each general practice pharmacist
      maintained a daily activity diary, which was subsequently analysed. RESULTS: The
      general practice pharmacists' activities were categorised as quality of practice
      (37%), administration (34%), medication review (19%) and patient education (11%).
      Within the quality of practice category, most time was spent conducting clinical
      audits (47%). Over the course of the six months, time spent on administration
      decreased, while time communicating with general practitioners (GPs) on clinical
      issues increased. DISCUSSION: The general practice pharmacists conducted a range
      of predominantly clinically related activities involving their expertise in the
      quality use of medications. Involvement in clinical activities to support GPs
      increased with time working in the practice. Randomised controlled trials are
      required to collect clinical outcomes and determine which activities conducted by
      pharmacists are most beneficial to Australian patients and GPs.

PMID- 30114893
TI  - Junior doctors, burnout and wellbeing: Understanding the experience of burnout in
      general practice registrars and hospital equivalents.
AB  - BACKGROUND AND OBJECTIVES: Australian junior doctors are stressed and report high
      rates of burnout. The aim of this study was to understand the experience of
      burnout in general practice registrars and hospital equivalents. METHOD:
      Qualitative, semi-structured interviews were completed until saturation and
      thematically analysed. RESULTS: Stress was common among the interviewees, and the
      causes of stress were multifactorial. The junior doctors were aware of burnout
      prevention strategies but were not always effectively undertaking them. They were
      more likely to be feeling stressed when their expectations regarding workplace
      support were not met and when they believed they were practising beyond the level
      of their own abilities. DISCUSSION: On the basis of our findings, we propose a
      multifactorial model of junior doctor burnout. This model warrants further
      investigation to inform policies to reduce burnout in junior doctors and ensure a
      research-based solution is found to the progressive concerns regarding junior
      doctor burnout and suicides.

PMID- 30114894
TI  - Medication non-adherence in a cohort of chronically ill Australians: A case of
      missed opportunities.
AB  - BACKGROUND AND OBJECTIVES: This study investigated the effect of management -
      including home medicines reviews and chronic disease management plans funded
      through the Medicare Benefits Schedule - on self-reported medication non
      adherence. METHOD: An observational cohort study including 244 individuals with
      an exacerbation of chronic illness enrolled into the Care Navigation randomised
      controlled trial of integrated care. Non-adherence was measured using the Morisky
      Greene-Levine self-reported adherence tool. RESULTS: The cohort comprised an
      equal number of older men and women with, on average, three chronic diseases,
      receiving between five and 10 unique medications each month and visiting a
      general practitioner (GP) more than 50 times in the year prior to completing the
      questionnaire. Forty per cent reported non-adherence, which was greater in males
      (relative risk [RR]: 1.73; 95% confidence interval [CI]: 1.25, 2.54) and in
      patients reporting a recent fall (RR 1.40; 95% CI: 1.02, 1.89). GP-initiated
      chronic disease management programs did not influence adherence. DISCUSSION:
      Despite almost weekly contact with GPs, two in five patients were non-adherent.
      Better methods of encouraging adherence are needed.

PMID- 30114895
TI  - Impact of training for general practitioners on their mental health services: The
      Hong Kong experience.
AB  - METHOD: A questionnaire survey was conducted among GPs. Of the 516 respondents,
      76 (14.7%) had attended a one-year postgraduate mental health training course.
      RESULTS: The GPs with mental health training saw significantly more patients with
      mental health problems per week (median class 11-15 versus 6-10) and treated a
      higher percentage of patients with mental health problems (median class 41-60%
      versus 21-40%). The differences remained significant, with odds ratios of 2.6 for
      both indicators after controlling for gender, healthcare setting and years of
      practice. DISCUSSION: Policies should promote training of GPs as part of the
      increasing workforce for mental healthcare. Estimated from the results, GPs with
      mental health training have nearly triple the number of consultations related to
      mental health, compared with other GPs (340 versus 120 per year).

PMID- 30114896
TI  - The youth-centricity of three university-associated general practices.
AB  - BACKGROUND AND OBJECTIVES: Young people are poor attenders of mainstream general
      practice; however, university general practices may be an exception, given the
      age demographic of the population from which they draw patients. The objective of
      this article was to explore the youth-centricity of 12 months of encounter data
      from three university-associated general practices: Queensland University of
      Technology (QUT) in Brisbane, University of New South Wales (UNSW) in Sydney and
      the University of Melbourne (UniMelb). METHOD: Encounter data from January to
      December 2016 were extracted from information management software and analysed
      using SPSS Statistics 24. RESULTS: The highest percentages of encounters were
      with patients aged 20-24 years at QUT (39.8%), UNSW (40.6%) and UniMelb (40%).
      DISCUSSION: The age encounter data from the general practices associated with
      QUT, UNSW and UniMelb demonstrate their youth-centricity, with almost 50% of
      encounters with patients aged 15-24 years. This result is unsurprising given the
      age demographic from which these practices draw patients, but a proportional
      under-representation of younger students suggests possible access issues that
      require further research. Questions regarding the role of these and other
      Australian university-associated general practices in the health of young people
      attending university are signposted for future enquiry.

PMID- 30114897
TI  - Workplace issues in general practice.

PMID- 30114899
TI  - Conducting simulation studies for computerized adaptive testing using SimulCAT:
      an instructional piece.
AB  - Computerized adaptive testing (CAT) technology is widely used in a variety of
      licensing and certification examinations administered to health professionals in
      the United States. Many more countries worldwide are expected to adopt CAT for
      their national licensing examinations for health professionals due to its reduced
      test time and more accurate estimation of a test-taker's performance ability.
      Continuous improvements to CAT algorithms promote the stability and reliability
      of the results of such examinations. For this reason, conducting simulation
      studies is a critically important component of evaluating the design of CAT
      programs and their implementation. This report introduces the principles of
      SimulCAT, a software program developed for conducting CAT simulation studies. The
      key evaluation criteria for CAT simulation studies are explained and some
      guidelines are offered for practitioners and test developers. A step-by-step
      tutorial example of a SimulCAT run is also presented. The SimulCAT program
      supports most of the methods used for the 3 key components of item selection in
      CAT: the item selection criterion, item exposure control, and content balancing.
      Methods for determining the test length (fixed or variable) and score estimation
      algorithms are also covered. The simulation studies presented include output
      files for the response string, item use, standard error of estimation, Newton
      Raphson iteration information, theta estimation, the full response matrix, and
      the true standard error of estimation. In CAT simulations, one condition cannot
      be generalized to another; therefore, it is recommended that practitioners
      perform CAT simulation studies in each stage of CAT development.

PMID- 30114898
TI  - The Effect of Trimebutine on the Overlap Syndrome Model of Guinea Pigs.
AB  - Background/Aims: Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are
      common gastrointestinal (GI) disorders and these patients frequently overlap.
      Trimebutine has been known to be effective in controlling FD co-existing diarrhea
      dominant IBS, however its effect on overlap syndrome (OS) patients has not been
      reported. Therefore, we investigated the effect of trimebutine on the model of OS
      in guinea pigs. Methods: Male guinea pigs were used to evaluate the effects of
      trimebutine in corticotropin-releasing factor (CRF) induced OS model. Different
      doses (3, 10, and 30 mg/kg) of trimebutine were administered orally and incubated
      for 1 hour. The next treatment of 10 MUg/kg of CRF was intraperitoneally injected
      and stabilized for 30 minutes. Subsequently, intragastric 3 mL charcoal mix was
      administered, incubated for 10 minutes and the upper GI transit analyzed. Colonic
      transits were assessed after the same order and concentrations of trimebutine and
      CRF treatment by fecal pellet output assay. Results: Different concentrations (1,
      3, and 10 MUg/kg) of rat/human CRF peptides was tested to establish the OS model
      in guinea pigs. CRF 10 MUg/kg was the most effective dose in the experimental OS
      model of guinea pigs. Trimebutine (3, 10, and 30 mg/kg) treatment significantly
      reversed the upper and lower GI transit of CRF induced OS model. Trimebutine
      significantly increased upper GI transit while it reduced fecal pellet output in
      the CRF induced OS model. Conclusions: Trimebutine has been demonstrated to be
      effective on both upper and lower GI motor function in peripheral CRF induced OS
      model. Therefore, trimebutine might be an effective drug for the treatment of OS
      between FD and IBS patients.

PMID- 30114900
TI  - A novel tool for evaluating non-cognitive traits of doctor of physical therapy
      learners in the United States.
AB  - PURPOSE: The primary aim of this study was to develop a survey addressing an
      individual's non-cognitive traits, such as emotional intelligence, interpersonal
      skills, social intelligence, psychological flexibility, and grit. Such a tool
      would provide beneficial information for the continued development of admissions
      standards and would help better capture the full breadth of experience and
      capabilities of applicants applying to doctor of physical therapy (DPT) programs.
      METHODS: This was a cross-sectional survey study involving learners in DPT
      programs at 3 academic institutions in the United States. A survey was developed
      based on established non-proprietary, non-cognitive measures affiliated with
      success and resilience. The survey was assessed for face validity, and
      exploratory factor analysis (EFA) was used to identify subgroups of factors based
      on responses to the items. RESULTS: A total of 298 participants (90.3%) completed
      all elements of the survey. EFA yielded 39 items for dimensional assessment with
      regression coefficients < 0.4. Within the 39 items, 3 latent constructs were
      identified: adaptability (16 items), intuitiveness (12 items), and engagement (11
      items). CONCLUSION: This preliminary non-cognitive assessment survey will be able
      to play a valuable role in DPT admissions decisions following further examination
      and refinement.

PMID- 30114902
TI  - Low-Frequency Noise in Graphene Tunnel Junctions.
AB  - Graphene tunnel junctions are a promising experimental platform for single
      molecule electronics and biosensing. Ultimately their noise properties will play
      a critical role in developing these applications. Here we report a study of
      electrical noise in graphene tunnel junctions fabricated through feedback
      controlled electroburning. We observe random telegraph signals characterized by a
      Lorentzian noise spectrum at cryogenic temperatures (77 K) and a 1/ f noise
      spectrum at room temperature. To gain insight into the origin of these noise
      features, we introduce a theoretical model that couples a quantum mechanical
      tunnel barrier to one or more classical fluctuators. The fluctuators are
      identified as charge traps in the underlying dielectric, which through random
      fluctuations in their occupation introduce time-dependent modulations in the
      electrostatic environment that shift the potential barrier of the junction.
      Analysis of the experimental results and the tight-binding model indicate that
      the random trap occupation is governed by Poisson statistics. In the 35 devices
      measured at room temperature, we observe a 20-60% time-dependent variance of the
      current, which can be attributed to a relative potential barrier shift of between
      6% and 10%. In 10 devices measured at 77 K, we observe a 10% time-dependent
      variance of the current, which can be attributed to a relative potential barrier
      shift of between 3% and 4%. Our measurements reveal a high sensitivity of the
      graphene tunnel junctions to their local electrostatic environment, with
      observable features of intertrap Coulomb interactions in the distribution of
      current switching amplitudes.

PMID- 30114901
TI  - Color-Coded Single-Particle Pyrophosphate Assay with Dark-Field Optical
      Microscopy.
AB  - In this work, we demonstrate a convenient yet sensitive color-coded single
      particle detection method for the quantification of pyrophosphate (PPi) by using
      single gold nanoparticle (GNP) as the probe. The design is based on GNP-dependent
      catalytic deposition of Cu onto the surface of GNPs with reduced nicotinamide
      adenine dinucleotide (NADH). Without PPi, Cu2+ can be directly reduced to Cu0
      through the gold-catalyzed oxidization of NADH. In the presence of PPi, the
      coating process is impeded due to the strong coordination capability of PPi with
      Cu2+. The selective coating of Cu shell onto the GNPs surface results in the
      extraordinary red-shift of localized surface plasmon resonance from individual
      GNPs. By quantitatively counting the fraction of yellow particles with color
      coded dark-field optical microscopy, the trace amounts of PPi in solution can be
      accurately quantified. The limit-of-detection is as low as 1.49 nM with a linear
      dynamic range of 0-4.29 MUM, which is much lower than the spectroscopic
      measurements in bulk solution. In artificial urine sample, good recovery
      efficiency was achieved. As a consequence, the method demonstrated herein will
      find promising applications for the ultrasensitive detection of target
      biomolecules under biological milieu in the future.

PMID- 30114903
TI  - Understanding the Effect of Conformation on Hole Delocalization in
      Poly(dimethylsilane).
AB  - Density functional theory calculations confirm that the simple explanation of the
      origin of the striking conformational dependence of sigma-electron
      localization/delocalization in polysilanes offered by the extremely simple Ladder
      C model is correct.

PMID- 30114904
TI  - Large Scale Synthetic Site Saturation GPCR Libraries Reveal Novel Mutations That
      Alter Glucose Signaling.
AB  - Site saturation mutagenesis (SSM) is a powerful mutagenesis strategy for protein
      engineering and directed evolution experiments. However, limiting factors using
      this method are either biased representation of variants, or limiting library
      size. To overcome these hurdles, we generated large scale targeted synthetic SSM
      libraries using massively parallel oligonucleotide synthesis and benchmarked this
      against an error-prone (epPCR) library. The yeast glucose activated GPCR-Gpr1 was
      chosen as a prototype to evolve novel glucose sensors. We demonstrate superior
      variant representation and several unique hits in the synthetic library compared
      to the PCR generated library. Application of this mutational approach further
      builds the possibilities of synthetic biology in tuning of a response to known
      ligands and in generating biosensors for novel ligands.

PMID- 30114905
TI  - Study on the Thermodynamics of Polymer Crystallization Based on Twin-Lattice
      Model.
AB  - Polymer crystallization is the most important part in determining the performance
      of polymeric materials. The twin-lattice model originally provided by Lennard
      Jones and Devonshire, developed by Pople and Karasz and other researchers, is
      extended for describing the thermodynamics of polymer crystallization. The
      positional order of segments and the orientational order of bonds are considered
      in this model. The free energy of polymers is obtained by further introducing the
      conformational energy and entropy, and thus a new parameter is defined, which is
      the ratio of conformational energy and positional diffusion energy. We studied
      two kinds of processes in polymer crystallization, including the process with
      plastic crystal phase and without any mesophases. The choice of crystallizing
      process is determined by the magnitude of lattice energy and conformational
      energy. The solid-solid transition from crystal to plastic crystal shows a
      significant dependence on the conformational energy. Considering data
      reliability, n-paraffins are chosen as the representation of polymers to compare
      the predictions of the model with experimental observations. We predict the
      number of carbons beyond which the rotator phase disappears, which is quite in
      agreement with the experiments. These calculations and results show this model
      can provide a new understanding to the crystallization of polymers.

PMID- 30114906
TI  - Development of an Analytical Method for Estimating Three-Dimensional Distribution
      of Sediment-Associated Radiocesium at a Reservoir Bottom.
AB  - After the Fukushima Daiichi Nuclear Power Station accident, the distributions of
      sediment-associated radiocesium were investigated to evaluate the dispersion and
      accumulation of radiocesium in the reservoir field. To develop an analytical
      method for measuring the horizontal and vertical distributions of radiocesium on
      a wide scale, we obtained 253 gamma-ray spectra at the bottoms of 64 ponds in
      Fukushima during 2014-2016 by using a NaI(Tl) scintillation detector. For
      visualizing horizontal distribution, the correlation between detector counting
      rate and radiocesium concentration of the bottom sediment was confirmed. In
      estimating vertical distribution, the depth profile of sediment-associated
      radiocesium was found to be correlated to the intensities of scattered and photo
      peaks. Good agreement was observed between the results of in situ spectrometry
      and core sampling. These results indicate that the developed method is suitable
      for understanding the behavior of radiocesium and determining whether
      decontamination of reservoirs is required.

PMID- 30114907
TI  - An Integrated, High-Throughput Strategy for Multiomic Systems Level Analysis.
AB  - Proteomics, metabolomics, and transcriptomics generate comprehensive data sets,
      and current biocomputational capabilities allow their efficient integration for
      systems biology analysis. Published multiomics studies cover methodological
      advances as well as applications to biological questions. However, few studies
      have focused on the development of a high-throughput, unified sample preparation
      approach to complement high-throughput omic analytics. This report details the
      automation, benchmarking, and application of a strategy for transcriptomic,
      proteomic, and metabolomic analyses from a common sample. The approach, sample
      preparation for multi-omics technologies (SPOT), provides equivalent performance
      to typical individual omic preparation methods but greatly enhances throughput
      and minimizes the resources required for multiomic experiments. SPOT was applied
      to a multiomics time course experiment for zinc-treated HL-60 cells. The data
      reveal Zn effects on NRF2 antioxidant and NFkappaB signaling. High-throughput
      approaches such as these are critical for the acquisition of temporally resolved,
      multicondition, large multiomic data sets such as those necessary to assess
      complex clinical and biological concerns. Ultimately, this type of approach will
      provide an expanded understanding of challenging scientific questions across many
      fields.

PMID- 30114908
TI  - Otherwise Unstable Structures Self-Assemble in the Cavities of Cuboctahedral
      Coordination Cages.
AB  - We present a method for the directed self-assembly of interlocked structures and
      coordination complexes in a set of metal-organic hosts. New homo- and
      heteroleptic metal complexes-species that cannot be prepared outside-form within
      the cavities of cuboctahedral coordination cages. When linear bidentate guests
      and macrocycles are sequentially introduced to the host, a rotaxane is threaded
      internally; the resulting ternary host-guest complex is a new kind of molecular
      gyroscope. Tetradentate guests segregate the cavities of these cages into
      distinct spaces, promoting new stoichiometries and modes of ligand binding to
      metal ions. The behaviors of bound complexes were observed to alter markedly as a
      result of confinement: In situ oxidations and spin transitions, neither of which
      occur ex situ, were both observed to proceed. By providing a tailored space for
      new modes of coordination-driven self-assembly, the inner phases of cuboctahedral
      coordination cages provide a new medium for synthetic coordination chemistry.

PMID- 30114909
TI  - Conformational Transitions of Melittin between Aqueous and Lipid Phases:
      Comparison of Simulations with Experiments.
AB  - Peptides are promising drug candidates with advantageous therapeutic properties.
      However, their inherent flexibility makes the development of structure-activity
      relationships difficult. Molecular dynamics simulations have been widely used to
      study peptide conformations, but they are limited by force field parameters. We
      explore the ability of nine combinations of commonly used protein, lipid, and
      water force field models (ff99/tip3p, ff14SB/tip3p, c22/tip3p, c22/tips3p,
      c36/tip3p, c36/tips3p, c36m/tip3p, c36m/tips3p, and g53a6/spc) in capturing the
      conformational dynamics of the antimicrobial peptide melittin between the aqueous
      and model membrane environments. Circular dichroism experiments of melittin
      displayed a structural transition from a random coil in an aqueous solution to a
      helix in the presence of a model membrane. Of the protein/lipid/water models that
      we examined, c22 with the tips3p water model correctly recapitulated the
      experimentally observed disordered conformations in an aqueous solution and
      helical conformations in the presence of the model membrane, followed by
      c36/tips3p. Hydration analysis revealed that the tips3p water model leads to
      stronger peptide-water interactions, which, in turn, better describe the
      solvation and its effects on conformational distributions in aqueous and membrane
      environments. The results of this study reveal the secondary structure
      preferences of various force fields and emphasize the role of hydration and
      microenvironment in modulating peptide conformations.

PMID- 30114910
TI  - Development of RBC Membrane Antigen Arrays for Validating Blood Grouping
      Reagents.
AB  - Antibody reagents have been remained as a standard approach to characterize blood
      group (BG) antigens in clinic. The specificity and cross-reactivity of these BG
      antibodies are routine detected using the gel microcolumn assay (GMA). However,
      the GMA is neither specific nor sensitive, thus increasing the risk of improperly
      matched RBC transfusions. In this work, we describe a bead-based RBC membrane
      antigen array to detect BG antibody-antigen binding with ~700-fold higher
      sensitivity and dynamic range than the GMA. RBC membrane antigen arrays were
      fabricated using fragmented RBC membranes highly enriched in BG panel antigens.
      The arrays were then used to screen the interactions of 15 BG reagents to three
      antigen panels. The majority of the antibody reactions (i.e., 86.7%; 39/45)
      aligned with those obtained with the GMA. The six cross-reactive, nonspecific
      antibody reactions identified only by our arrays (i.e., 13.3%; 6/45) were
      confirmed by agglutination inhibition and genotyping assays. These results
      demonstrate that our RBC membrane antigen array has great potential in screening
      BG antibodies and improving the safety of RBC transfusions.

PMID- 30114911
TI  - Reversible Supramolecular Assembly of Velvet Worm Adhesive Fibers via
      Electrostatic Interactions of Charged Phosphoproteins.
AB  - Velvet worms secrete a fluid hunting slime comprised of a dispersion of
      nanoglobules that form microfibers under small mechanical shear forces,
      facilitating the rapid formation of stiff biopolymeric fibers. Here, we
      demonstrate that the nanoglobules are held together and stabilized as a
      dispersion by electrostatic interactions reminiscent of coacervate-based natural
      adhesives. Variation of ionic strength and pH affects the stability of
      nanoglobules and their ability to form fibers. Fibers mainly consist of large
      (~300 kDa), highly charged proteins, and current biochemical analysis reveals a
      high degree of protein phosphorylation and presence of divalent cations. Taken
      together, we surmise that polyampholytic protein sequences, phosphorylated sites,
      and ions give rise to transient ionic cross-linking, enabling reversible curing
      of ejected slime into high-stiffness fibers following dehydration. These results
      provide a deeper understanding of velvet worm adhesive fibers, which may
      stimulate new routes toward mechanoresponsive and sustainable materials.

PMID- 30114912
TI  - Terminal Thiolate-Dominated H/D Exchanges and H2 Release: Diiron Thiol-Hydride.
AB  - To determine the reaction pathways at a metal-ligand site in enzymes, we
      incorporated a terminal thiolate site into a diiron bridging hydride. Trithiolato
      diiron hydride, (MU-H)Fe2(pdt)(dppbz)(CO)2(SR) (1(MU-H)) [pdt2- = 1,3-(CH2)3S22-,
      dppbz = 1,2-C6H4(PPh2)2, RS- = 1,2-Cy2PC6H4S-)], was synthesized directly by
      photoassisted oxidative addition of 1,2-Cy2PC6H4SH to Fe2(pdt)(dppbz)(CO)4. The
      terminal thiolate in 1(MU-H) undergoes protonation, affording a thiol-hydride
      complex [1(MU-H)H]+. Placing an acidic SH site adjacent to the Fe-H-Fe site
      allows intramolecular thiol-hydride coupling and releases H2 from [1(MU-H)H]+. A
      diiron eta2-H2 intermediate in the formation of H2 is proposed, and is evidenced
      by the H/D exchange reactions of [1(MU-H)H]+ with D2, D2O, and CD3OD. Isotopic
      exchange in [1(MU-D)H]+ is driven by an equilibrium isotope effect with 2.1
      kJ/mol difference in free energy that favors [1(MU-H)D]+. [1(MU-H)H]+ catalyzes
      H/D scrambling between H2 and D2O or CD3OD to produce HD. The reactions based on
      such a "proton-hydride" model provide insights into the reversible heterolytic
      cleavage of H2 by H2ases.

PMID- 30114913
TI  - Stable Covalent Organic Frameworks as Efficient Adsorbents for High and Selective
      Removal of an Aryl-Organophosphorus Flame Retardant from Water.
AB  - A critical challenge in environmental remediation is the design of adsorbents
      with proper pore size for the removal of organic pollutants. Three covalent
      organic frameworks (COFs) with different pore sizes were successfully prepared by
      a room-temperature solution-suspension method and used to remove a typical aryl
      organophosphorus flame retardant [triphenyl phosphate (TPhP)] from aqueous
      solution. The prepared COFs showed strong acid resistance and thermal stability.
      The 1,3,5-triformylphloroglucinol (TFP) reacted with benzidine (BD) (COF2) and
      exhibited the highest sorption capacity for TPhP, followed by the reaction of TFP
      and 4,4"-diamino- p-terphenyl (DT) (COF3), and the reaction of TFP and p
      phenylenediamine (COF1). Their adsorption equilibriums were achieved within 12 h,
      and COFs with a larger pore size have higher initial sorption rate but longer
      time to reach sorption equilibrium. According to the Langmuir fitting, the
      maximum sorption capacities of three COFs for TPhP were 86.1, 387.2, and 371.2
      mg/g, respectively. The density functional theory calculation verified that COF1
      with a small pore size prevents TPhP molecules from entering the pores, resulting
      in extremely low sorption capacity, whereas a relatively too large pore size
      (COF3) will decrease the sorption energy, which is also not conducive to the
      adsorption of TPhP. Moreover, the prepared COFs can selectively adsorb TPhP in
      the presence of coexisting compounds and had high removal of TPhP from actual
      municipal wastewater, showing a promising application potential for selective
      removal of micropollutants from water by precisely controlling the COF structure.

PMID- 30114915
TI  - Development of Antimicrobial and Antifouling Universal Coating via Rapid
      Deposition of Polydopamine and Zwitterionization.
AB  - Biomaterials-associated infections (BAIs) are related to bacterial colonization
      on medical devices, which lead to a serious medical burden, such as increased
      healthcare cost, prolonged hospital stays, and high mortality and morbidity. To
      reduce the risk of infections, in this work, a new approach which makes use of a
      bioinspired coating with dual antimicrobial and antifouling functions was
      developed through rapid deposition of functional polydopamine (pDA) and
      antimicrobial copper ions, and subsequent conjugation of zwitterionic antifouling
      sulfobetaine (SB) moieties by the aza-Michael addition reaction. pDA permits
      surface-independent versatile functionalization on a variety of substrates, such
      as TiO2, SiO2, gold, plastics, and Nitinol alloy. The characterizations for
      chemical elemental compositions and hydrophilicity by X-ray photoelectron
      spectroscopy and contact angle goniometer, respectively, indicating the
      successful grafting of SB moieties and the presence of copper ions in the pDA
      adlayers. Ellipsometric thicknesses of the thin films were followed to monitor
      the formation of pDA films and the changes after the post conjugation. UV-vis
      spectroscopy and inductively coupled plasma-mass spectrometry revealed the
      coordination structure of catechol-Cu, and release profile of Cu2+ from the
      constructed functional coatings. The superhydrophilic and charge-balanced SB
      interface allowed effective resistance of bacterial adsorption. Intriguingly, we
      scrutinized that the release of bactericidal copper ions enables killing the
      residual amount of adsorbed bacteria. Moreover, viability tests for fibroblast
      cells indicate the excellent biocompatibility of the developed medical coatings.
      For real-world implementation, the antifouling and antimicrobial coatings were
      applied on commercially available silicone-based urinary catheters, and the
      existence of bacteria was evaluated by using the plate-counting assay. The
      results showed an undetectable level of living bacteria. Consequently, the dual
      functional medical coating offers a promising approach to eliminate BAIs for
      practical applications.

PMID- 30114916
TI  - Lithium-Ion-Transfer Kinetics of Single LiFePO4 Particles.
AB  - The Li-ion desertion process of a single LiFePO4 particle with a diameter of 400
      nm in aqueous media at high potential is investigated by stochastic collision of
      the particle at a microelectrode. No extra additive, such as polymeric binder or
      conductive carbon, is involved in this stochastic measurement. The ion diffusion
      inside the particle is proved to be the rate-determining step that limits the
      discharge rate of batteries using LiFePO4 in an aqueous environment. This result
      offers guidance for exploring the most effective enhancement of Li-ion batteries.
      Moreover, this general method can be applied to study the electrochemical
      behavior of other electrode materials as an alternative and complementary route.

PMID- 30114914
TI  - Comparing Multiple Machine Learning Algorithms and Metrics for Estrogen Receptor
      Binding Prediction.
AB  - Many chemicals that disrupt endocrine function have been linked to a variety of
      adverse biological outcomes. However, screening for endocrine disruption using in
      vitro or in vivo approaches is costly and time-consuming. Computational methods,
      e.g., quantitative structure-activity relationship models, have become more
      reliable due to bigger training sets, increased computing power, and advanced
      machine learning algorithms, such as multilayered artificial neural networks.
      Machine learning models can be used to predict compounds for endocrine disrupting
      capabilities, such as binding to the estrogen receptor (ER), and allow for
      prioritization and further testing. In this work, an exhaustive comparison of
      multiple machine learning algorithms, chemical spaces, and evaluation metrics for
      ER binding was performed on public data sets curated using in-house
      cheminformatics software (Assay Central). Chemical features utilized in modeling
      consisted of binary fingerprints (ECFP6, FCFP6, ToxPrint, or MACCS keys) and
      continuous molecular descriptors from RDKit. Each feature set was subjected to
      classic machine learning algorithms (Bernoulli Naive Bayes, AdaBoost Decision
      Tree, Random Forest, Support Vector Machine) and Deep Neural Networks (DNN).
      Models were evaluated using a variety of metrics: recall, precision, F1-score,
      accuracy, area under the receiver operating characteristic curve, Cohen's Kappa,
      and Matthews correlation coefficient. For predicting compounds within the
      training set, DNN has an accuracy higher than that of other methods; however, in
      5-fold cross validation and external test set predictions, DNN and most classic
      machine learning models perform similarly regardless of the data set or molecular
      descriptors used. We have also used the rank normalized scores as a performance
      criteria for each machine learning method, and Random Forest performed best on
      the validation set when ranked by metric or by data sets. These results suggest
      classic machine learning algorithms may be sufficient to develop high quality
      predictive models of ER activity.

PMID- 30114917
TI  - Progression of Self-Assembly of Amelogenin Protein Supramolecular Structures in
      Simulated Enamel Fluid.
AB  - Mechanisms of protein-guided mineralization in enamel, leading to organized
      fibrillar apatite nanocrystals, remain elusive. In vitro studies reveal
      recombinant human amelogenin (rH174), a matrix protein templating this process,
      self-assembles into a variety of structures. This study endeavors to clarify the
      self-assembly of rH174 in physiologically relevant conditions. Self-assembly in
      simulated enamel fluid was monitored up to 2 months. At alkali (7.3-8.7) and
      acidic (5.5-6.1) pH ranges, a distinct progression in formation was observed from
      nanospheres (17-23 nm) to intermediate-length nanorods, concluding with the
      formation of long 17-18 nm wide nanoribbons decorated with nanospheres. Assembly
      in acidic condition progressed quicker to nanoribbons with fewer persistent
      nanospheres. X-ray diffraction exhibited reflections characteristic of
      antiparallel beta-sheets (4.7 and 9.65 A), supporting the model of amyloid-like
      nanoribbon formation. This is the first observation of rH174 nanoribbons at
      alkaline pH as well as concurrent nanosphere formation, indicating both
      supramolecular structures are stable together under physiological conditions.

PMID- 30114918
TI  - Ultrafast Energy Dissipation via Coupling with Internal and External Phonons in
      Two-Dimensional MoS2.
AB  - Atomically thin two-dimensional materials have emerged as a promising system for
      optoelectronic applications; however, the low quantum yield, mainly caused by
      nonradiative energy dissipation, has greatly limited practical applications. To
      reveal the details for nonradiative energy channels, femtosecond pump-probe
      spectroscopy with a detection wavelength ranging from visible to near-infrared to
      mid-infrared is performed on few-layer MoS2. With this method, the many-body
      effects, occupation effects, and phonon dynamics are clearly identified. In
      particular, thermalization of the MoS2 lattice via electron-phonon scattering is
      responsible for a redshift of the exciton resonance energy observed within tens
      to hundreds of picoseconds after photoexcitation, which provides a direct real
      time sensor for measuring the change in lattice temperature. We find that the
      excess energy from the cooling of hot carriers and the formation of bound
      carriers is efficiently transferred to the internal phonon system within 2 ps,
      while that from Shockley-Read-Hall recombination (~9 ps) is mainly dissipated
      from the MoS2 surfaces to external phonons.

PMID- 30114919
TI  - Scalable and Tunable Periodic Graphene Nanohole Arrays for Mid-Infrared
      Plasmonics.
AB  - Despite its great potential for a wide variety of devices, especially mid
      infrared biosensors and photodetectors, graphene plasmonics is still confined to
      academic research. A major reason is the fact that, so far, expensive and low
      throughput lithography techniques are needed to fabricate graphene
      nanostructures. Here, we report for the first time a detailed experimental study
      on electrostatically tunable graphene nanohole array surfaces with periods down
      to 100 nm, showing clear plasmonic response in the range ~1300-1600 cm-1, which
      can be fabricated by a scalable nanoimprint technique. Such large area plasmonic
      nanostructures are suitable for industrial applications, for example, surface
      enhanced infrared absorption (SEIRA) sensing, as they combine easy design,
      extreme field confinement, and the possibility to excite multiple plasmon modes
      enabling multiband sensing, a feature not readily available in nanoribbons or
      other localized resonant structures.

PMID- 30114920
TI  - Redox-Responsive Polymer Template as an Advanced Multifunctional Catalyst Support
      for Silver Nanoparticles.
AB  - Hybridization of metal nanoparticles (NPs) with redox-switchable polymer supports
      not only mitigates their aggregation, but also introduces interfacial electron
      pathways desirable for catalysis and numerous other applications. The large
      surface area and surface accessible atoms for noble metal nanoparticles (e.g.,
      Ag, Au, Pt) offer promising opportunities to address challenges in catalysis and
      environmental remediation. Herein, AgNPs were supported onto redox-switchable
      polyaniline that acts as an advanced multifunctional conducting template for
      enhanced catalytic activity. At the initial stage of reduction of Ag+,
      leucoemeraldine is oxidized in situ to pernigraniline (PG), which acts as
      interfacial pathway between NPs for electron transport. With the contribution of
      BH4-, PG acts as an electron-acceptor site, which creates interfacial electron
      hole pairs, serving as additional active catalytic reduction sites. The use of a
      redox-responsive composite system as a template enhances catalyst performance
      through adjustable charge injection across interfacial sites, along with catalyst
      reusability for the reduction of 4-nitrophenol (4-NPh). Strikingly, from X-ray
      photoelectron spectroscopy results it was observed that in situ reduction of Ag+
      onto the conductive polymer alters the electronic character of the catalyst. The
      unique multielectronic effects of such Ag-supported NPs enrich the scope of such
      catalytic systems via a tunable interface, diversified catalytic activity, fast
      kinetics, minimization of AgNPs aggregation, and maintenance of high stability
      under multiple reaction cycles.

PMID- 30114921
TI  - Fe-Catalyzed Conversion of N2 to N(SiMe3)3 via an Fe-Hydrazido Resting State.
AB  - The catalytic conversion of N2 to N(SiMe3)3 by homogeneous transition metal
      compounds is a rapidly developing field, yet few mechanistic details have been
      experimentally elucidated for 3 d element catalysts. Herein we show that
      Fe(PP)2(N2) (PP = R2PCH2CH2PR2; R = Me, 1Me; R = Et, 1Et) are highly effective
      for the catalytic production of N(SiMe3)3 from N2 (using KC8/Me3SiCl), with the
      yields being the highest reported to date for Fe-based catalysts. We propose that
      N2 fixation proceeds via electrophilic Nbeta silylation and 1e- reduction to form
      unstable FeI(NN-SiMe3) intermediates, which disproportionate to 1Me/Et and
      hydrazido FeII[N-N(SiMe3)2] species (3Me/Et); the latter act as resting states on
      the catalytic cycle. Subsequent 2e- reduction of 3Me/Et leads to N-N scission and
      formation of [N(SiMe3)2]- and putative anionic Fe imido products. These
      mechanistic results are supported by both experiment and DFT calculations.

PMID- 30114925
TI  - Bisphosphonate Use in Pediatric Oncology for Pain Management.
AB  - The use of bisphosphonates for pain control in children with cancer is not
      extensively studied. We retrospectively evaluated 35 children with cancer treated
      with intravenous bisphosphonates for pain management at a single institution from
      1998 through 2015. We analyzed pain scores and opioid and adjuvant medication
      consumption before bisphosphonate administration, daily for 2 weeks, and at 3 and
      4 weeks after administration. We also determined the time interval between
      diagnosis and first administration of bisphosphonates and duration of life after
      bisphosphonate administration. Mean pain scores were 2.45 (+/-2.96) and 0.75 (+/
      1.69) before and 14 days after bisphosphonate administration, respectively ( P =
      .25), and morphine equivalent doses of opioids were 5.52 (+/-13.35) and 5.27 (+/
      9.77), respectively ( P = .07). Opioid consumption was significantly decreased at
      days 4 to 8, days 11 to 12, and week 3 after first bisphosphonate administration.
      The median duration of life after first bisphosphonate administration was 80
      days, indicating its use late in the course of treatment. Bisphosphonates did not
      significantly improve pain outcomes at 2 weeks, but opioid consumption was
      reduced at several time points during the first 3 weeks. The use of
      bisphosphonates earlier in the course of pediatric oncological disease should be
      evaluated in prospective investigations.

PMID- 30114926
TI  - Perfusion-CT analysis for assessment of hepatocellular carcinoma lesions:
      diagnostic value of different perfusion maps.
AB  - Background Computed tomography liver perfusion (CTLP) has been improved in recent
      years, offering a variety of perfusion-parametric maps. A map that better
      discriminates hepatocellular carcinoma (HCC) is still to be found. Purpose To
      compare different CTLP maps, regarding their ability to differentiate cirrhotic
      or non-cirrhotic parenchyma from malignant HCC. Material and Methods Twenty-six
      patients (11 cirrhotic) with 50 diagnosed HCC lesions, underwent CTLP on a 128
      row dual-energy CT system. Nine different maps were generated. Regions of
      interest (ROIs) were positioned on non-tumorous parenchyma and on HCCs found on
      previous magnetic resonance imaging. Perfusion parameters for non-cirrhotic and
      cirrhotic livers were compared. Receiver operating characteristic (ROC) analysis
      was employed to evaluate each map's ability to discriminate HCCs from non
      tumorous livers. Comparison of ROC curves was performed to evaluate statistical
      significance of differences in the discriminating efficiency of derived perfusion
      maps. Results Perfusion parameters for non-tumorous liver and HCCs recorded in
      cirrhotic patients did not significantly differ from corresponding values
      recorded in non-cirrhotic patients ( P > 0.05). The highest power for HCC
      discrimination was found for the maximum-slope-of-increase (MSI) parametric map,
      with estimated the area under ROC curve of 0.997. An MSI cut-off criterion of 2.2
      HU/s was found to provide 96% sensitivity and 100% specificity. Time to peak,
      blood flow, and transit time to peak were also found to have high discriminating
      power. Conclusion Among available CTLP-derived perfusion parameters, MSI was
      found to provide the highest diagnostic accuracy in discriminating HCCs from non
      tumorous parenchyma. Perfusion parameters for non-tumorous livers and HCCs were
      not found to significantly differ between cirrhotic and non-cirrhotic patients.

PMID- 30114922
TI  - Large-Scale Synthesis, Crystal Structure, and Optical Properties of the
      Ag146Br2(SR)80 Nanocluster.
AB  - Solving the atomic structure of large-sized metal nanoclusters is a highly
      challenging task yet critically important for understanding the properties and
      developing applications. Herein, we report a stable silver nanocluster
      Ag146Br2(SR)80 (where SR = 4-isopropylbenzenethiolate)-with its structure solved
      by X-ray crystallography. Gram-scale synthesis with high yield has been achieved
      by a one-pot reaction, which offers opportunities for functionalization and
      applications. This silver nanocluster possesses a core-shell structure with a
      Ag51 core surrounded by a shell of Ag95Br2S80. The Ag51 core can be viewed as a
      distorted decahedron, endowing this nanocluster with quantized electronic
      transitions. In the surface-protecting layer, five different types of S-Ag
      coordination modes are observed, ranging from the linear Ag-S-Ag to S-Ag3
      (triangle) and S-Ag4 (square). Furthermore, temperature-dependent optical
      absorption and ultrafast electron dynamics are conducted to explore the
      relationship between the properties and structure, demonstrating that the
      distorted metal core and "flying saucer"-like shape of this nanocluster have
      significant effects on the electronic behavior. A comparison with multiple sizes
      of Ag nanoclusters also provides some insights into the evolution from molecular
      to metallic behavior.

PMID- 30114928
TI  - Perfusion-sensitive parameters of intravoxel incoherent motion MRI in rectal
      cancer: evaluation of reproducibility and correlation with dynamic contrast
      enhanced MRI.
AB  - Background Intravoxel incoherent motion magnetic resonance imaging (IVIM-MRI)
      acquires tumor perfusion information without injection of contrast medium, which
      is promising in tumor assessment. However, its consistency with dynamic contrast
      enhanced MRI (DCE-MRI), a more widely used method for tumor perfusion evaluation,
      is not revealed in rectal cancer. Purpose In this study, we aimed to investigate
      the correlation of perfusion-sensitive parameters derived from IVIM-MRI with DCE
      MRI and measurement reproducibility of IVIM-MRI parameters in rectal cancer.
      Material and Methods Forty-seven rectal cancer patients underwent IVIM-MRI with
      16 b-values and DCE-MRI. The perfusion fraction ( f), pseudo-diffusion
      coefficient ( D*), and f. D* were measured by two radiologists independently and
      correlated with the transfer constant ( Ktrans), reflux constant ( kep), and
      extravascular extracellular fractional volume ( ve) obtained from DCE-MRI.
      Results Pearson's correlation analyses of IVIM-MRI and DCE-MRI parameters showed
      fair to moderate correlation between f and Ktrans ( r = 0.461, P = 0.001),
      followed by f and kep ( r = 0.430, P = 0.003), f.D*, and Ktrans ( r = 0.425, P =
      0.003), f.D*, and kep ( r = 0.384, P = 0.008). There was no significant
      correlation between ve and f, ve and D*, ve and f. D*, D* and Ktrans, and D* and
      kep. The reproducibility of IVIM-MRI measurements was moderate. For parameter f,
      intraclass correlation coefficient (ICC) = 0.71 (0.53-0.82), coefficient of
      variation (CV) = 13.05 +/- 0.02%, limit of agreement (LoA) = -0.05-0.04; for
      parameter D*, ICC = 0.55 (0.32-0.72), CV = 20.28 +/- 3.23%, LoA = -9.6-8.4.
      Conclusion Perfusion-sensitive parameters derived from IVIM-MRI correlated fairly
      to moderately with DCE-MRI in rectal cancer patients and showed moderate
      measurement reproducibility. IVIM-MRI supplements routine high-resolution MRI
      without contrast enhancement to provide information of tumor microcirculation.

PMID- 30114927
TI  - DCE-MR imaging of orbital lesions: diagnostic performance of the tumor flow
      residence time tau calculated by a multi-compartmental pharmacokinetic tumor
      model based on individual factors.
AB  - Background Differentiating benign from malignant orbital lesions by imaging and
      clinical presentation can be challenging. Purpose To differentiate benign from
      malignant orbital masses using dynamic contrast-enhanced magnetic resonance
      imaging (DCE-MRI) based on tumor flow residence time tau calculated with the aid
      of a pharmacokinetic tumor model. Material and Methods Sixty patients with
      orbital masses were investigated by 3-T MRI including dynamic sequences. The
      signal intensity-time curve after i.v. contrast medium administration within
      lesions was approximated by Gd-concentration profiles on the basis of model
      calculations where the tumor is embedded in a whole-body kinetic model. One
      output of the model was tumor flow residence time tau, defined as the ratio of
      the tumor volume and the tumor blood flow rate. Receiver operating characteristic
      (ROC) curves were used to analyze the diagnostic performance of tau. The results
      were compared with those of Ktrans, kep, ve, iAUC, and ADC. Results Thirty-one
      benign and 29 malignant orbital masses were identified (reference standard:
      histopathology, clinical characteristics). Mean tau was significantly longer for
      benign masses (94 +/- 48 s) than for malignant masses (21 +/- 19 s, P < 0.001).
      ROC analysis revealed the highest area under the curve (AUC = 0.94) for tau in
      orbital masses compared to standard methods. Conclusion Tumor flow residence
      times tau of benign and malignant orbital masses are valuable in the diagnostic
      work-up of orbital tumors. Measures of diagnostic accuracy were superior for tau
      compared to ADC, Ktrans, ve, and iAUC.

PMID- 30114929
TI  - Relationship between serum thyrotropin and urine albumin excretion in euthyroid
      subjects with diabetes.
AB  - Background Microalbuminuria represents vascular and endothelial dysfunction.
      Thyroid hormones can influence urine albumin excretion as it exerts crucial
      effects on the kidney and on the vascular system. This study explores the
      relationship between serum thyrotropin and urine albumin excretion in euthyroid
      patients with diabetes. Methods A total of 433 patients with type 1 or 2 diabetes
      were included in this retrospective cross-sectional study. Data included
      anthropometric measurements and biochemical parameters from diabetes clinic.
      Males with urine albumin creatinine ratio >2.5 and female's >3.5 mg/mmoL were
      considered to have microalbuminuria. Results 34.9% of the patients had
      microalbuminuria. Prevalence of microalbuminuria increased according to TSH
      quartiles (26.9, 34.6, 38.5 and 44.9%, P for trend = 0.02). In a fully adjusted
      logistic regression model, higher TSH concentrations were associated with high
      prevalence of microalbuminuria (adjusted odds ratio 2.06 [95% CI: 1.14-3.72]; P =
      0.02), while comparing the highest with the lowest quartile of TSH. Multiple
      linear regression analysis showed an independent association between serum TSH
      and urine albumin creatinine ratio (beta = 0.007, t = 2.03 and P = 0.04). The
      risk of having microalbuminuria was higher with rise in TSH concentration in
      patients with younger age (<65 years), raised body mass index (>=25 kg/m2),
      hypertension, type 2 diabetes and hyperlipidaemia and age was the most important
      determinant ( P for interaction = 0.02). Conclusion Serum TSH even in the
      euthyroid range was positively associated with microalbuminuria in euthyroid
      patients with diabetes independent of traditional risk factors. This relationship
      was strongest in patients with components of the metabolic syndrome.

PMID- 30114930
TI  - Circulating tumour DNA as a cancer biomarker.
AB  - Measurement of genetically altered DNA shed from tumours into the circulation can
      potentially provide a new generation of blood-based cancer biomarkers. Compared
      with tissue DNA biomarkers which require surgery or biopsy, samples for
      circulating tumour DNA assays can be obtained with minimal inconvenience and at
      lower cost. Furthermore, in contrast to tissue, the use of circulating tumour DNA
      allows serial monitoring, faster delivery of results and potentially provides an
      integrative representation of genetic alterations across all tumour sites within
      a patient. In contrast to existing protein-based cancer biomarkers, all of which
      can be produced by benign disease, circulating tumour DNA biomarkers would be
      expected to be more specific for malignancy. Furthermore, unlike the available
      blood cancer biomarkers, circulating tumour DNA can be used to predict response
      to specific therapies, identify mechanisms of therapy resistance and detect
      potentially actionable mutations. One of the first circulating tumour DNA assays
      recommended for clinical use involves EGFR mutation testing for predicting
      response to EGFR tyrosine kinase inhibitors in patients with advanced non-small
      cell lung cancer, especially when tumour tissue is unavailable. In order to
      accelerate the introduction of circulating tumour DNA assays into routine
      clinical use, laboratory medicine staff will have to undergo training in the use
      of polymerase chain reaction and DNA sequencing. Furthermore, existing
      circulating tumour DNA assays will need to be simplified, standardized, shown to
      have clinical utility, be made available at reasonable costs and be reimbursable.

PMID- 30114931
TI  - Parent descriptions of the presentation and management of anxiousness in children
      on the autism spectrum.
AB  - The complex interaction between anxiety and autism has led to debate about the
      presentation of anxiety in individuals on the spectrum and questions about the
      extent to which traditional checklists assess the entire range of symptomatology.
      Moreover, studies to date have not explored how the presentation of anxiety may
      differ between settings. Through a combination of open-ended questions, closed
      questions and standardised measures, parents of 173 children (aged 6-13) on the
      autism spectrum provided (1) descriptors of their child's anxiety at home, school
      and in the community and (2) strategies used to reduce their child's anxiety in
      each setting. Over half (52.6%) felt their child was anxious at home, 77.6% at
      school and 76.2% in the community. Parents reported differing presentations of
      anxiety between settings, with the majority of descriptions relating to
      observable, behavioural changes (e.g. hides/shuts down, repetitive behaviours)
      rather than cognitive or physiological signs. Parents also reported using
      different strategies across settings. The use of open-ended questions allowed the
      identification of signs of anxiety not explored within traditional questionnaires
      and highlighted the potential for signs to vary across settings. This knowledge
      is critical to inform the development or adaptations of anxiety measures and
      interventions.

PMID- 30114932
TI  - Autism at a glance: A pilot study optimizing thin-slice observations.
AB  - Borrowing from a clinical psychology observational methodology, thin-slice
      observations were used to assess autism characteristics in toddlers. Thin-slices
      are short observations taken from a longer behavior stream which are assigned
      ratings by multiple raters using a 5-point scale. The raters' observations are
      averaged together to assign a "thin-slice" value for each observation. In this
      study, a total of 60 toddlers were selected from a video archive: 20 children
      with typical development, 20 children with developmental language disorder, and
      20 children with autism. In the first part of this study, 20 raters observed
      small play segments between toddlers and an assessor. Raters assigned scores to
      each of the 60 toddlers on items related to autism symptomatology. Item analysis
      and generalizability and decision studies were conducted to determine the factor
      structure and optimal number of raters to achieve a stable estimate of autism
      characteristics. In the second part of the study, generalizability and decision
      studies were conducted to determine the most efficient and optimal combination of
      raters and naturalistic contexts. This pilot study provides recommendations for
      optimizing the utility of thin-slice observations for measuring autism
      symptomatology in young children.

PMID- 30114933
TI  - TEG-seq: an ion torrent-adapted NGS workflow for in cellulo mapping of CRISPR
      specificity.
AB  - GUIDE-seq was developed to detect CRISPR/Cas9 off-target. However, as originally
      reported, it was associated with a high level of nonspecific amplification. In an
      attempt to improve it, we developed target-enriched GUIDE-seq (TEG-seq). The
      sensitivity level reached 0.1-10 reads-per-million  depending on the NGS platform
      used, which was equivalent to 0.0002-1% measured by Targeted Amplicon-seq.
      Application of TEG-seq was demonstrated for the evaluation of various Cas9/gRNA
      configurations, which suggests delivery of Cas9/gRNA ribonucleoprotein results in
      significantly fewer off-targets than Cas9/gRNA plasmid. TEG-seq was also applied
      to 22 gRNAs with relatively high in silico ranking score that targeted the
      biological relevant SNPs. The result indicated the initial selection of gRNAs
      with high score is important, although it cannot exclude the possibility of off
      target.

PMID- 30114934
TI  - Assessment of the Stability of von Willebrand Profile Clotting Factors and
      Platelet Dense Granule Testing Following Air Transport.
AB  - The purpose of this study was to determine the reliability of test results
      dependent upon blood and plasma sample stability when shipped by airfreight
      courier for reference laboratory assessment. Of particular interest was
      evaluation of von Willebrand profile assays and platelet dense granule storage
      pool analysis. Peripheral venous blood was obtained from healthy volunteers. von
      Willebrand factor (VWF) activity, VWF antigen, and factor VIII coagulant activity
      assays were performed immediately following venipuncture with additional aliquots
      of plasma frozen and stored at -70 degrees C for subsequent analysis 48 hours
      later. One frozen aliquot was shipped via airfreight for analysis 48 hours later,
      with another frozen aliquot that remained on-site. Blood was also collected to
      enumerate platelet dense granules to determine whether shipment would affect
      results. Statistical analysis of all test results demonstrated significant
      correlation between immediately assayed samples and samples that were stored for
      48 hours at -70 degrees C ( P < .0001), or frozen and shipped on dry ice ( P <
      .0001) for analysis upon return to our laboratory. No difference was found in the
      mean number of platelet dense granules between samples retained in our laboratory
      or samples analyzed upon return of shipment ( P = .751).

PMID- 30114935
TI  - PTSD post-childbirth: a systematic review of women's and midwives' subjective
      experiences of care provider interaction.
AB  - OBJECTIVE: Review primary research regarding PTSD Post-Childbirth (PTSD-PC) that
      focussed on Quality of Provider Interaction (QPI) from the perspective of women
      who developed PTSD-PC, or midwives. BACKGROUND: Up to 45% of women find
      childbirth traumatic. PTSD-PC develops in 4% of women (18% in high-risk groups).
      Women's subjective experiences of childbirth are the most important risk factor
      in the development of PTSD-PC, with perceived QPI being key. METHODS: A
      systematic search was performed for PTSD-PC literature. Reviewed papers focussed
      on either women's subjective childbirth experiences, particularly QPI, or
      midwives' perspectives on QPI. Study quality was assessed using the Critical
      Appraisal Skills Programme (CASP) tools, and a narrative synthesis of findings
      produced. RESULTS: Fourteen studies were included. Three features of QPI
      contribute towards developing PTSD-PC: interpersonal factors; midwifery care
      factors; and lack of support. CONCLUSION: QPI is a significant factor in the
      development of PTSD-PC and the identified key features of QPI have potential to
      be modified by midwives. The development of guidelines for midwives should be
      grounded on evidence highlighted in this review, along with further high-quality
      qualitative research exploring QPI from the perspective of women with PTSD-PC,
      but also midwives' knowledge and needs regarding their role within QPI.

PMID- 30114936
TI  - Evaluation of a computer-based and counseling support intervention to improve HIV
      patients' viral loads.
AB  - We sought to integrate a brief computer and counseling support intervention into
      the routine practices of HIV clinics and evaluate effects on patients' viral
      loads. The project targeted HIV patients in care whose viral loads exceeded 1000
      copies/ml at the time of recruitment. Three HIV clinics initiated the
      intervention immediately, and three other HIV clinics delayed onset for 16 months
      and served as concurrent controls for evaluating outcomes. The intervention
      components included a brief computer-based intervention (CBI) focused on
      antiretroviral therapy adherence; health coaching from project counselors for
      participants whose viral loads did not improve after doing the CBI; and
      behavioral screening and palm cards with empowering messages available to all
      patients at intervention clinics regardless of viral load level. The analytic
      cohort included 982 patients at intervention clinics and 946 patients at control
      clinics. Viral loads were assessed at 270 days before recruitment, at time of
      recruitment, and +270 days later. Results indicated that both the control and
      intervention groups had significant reductions in viral load, ending with
      approximately the same viral level at +270 days. There was no evidence that the
      CBI or the targeted health coaching was responsible for the viral reduction in
      the intervention group. Results may stem partially from statistical regression to
      the mean in both groups. Also, clinical providers at control and intervention
      clinics may have taken action (e.g., conversations with patients, referrals to
      case managers, adherence counselors, mental health, substance use specialists) to
      help their patients reduce their viral loads. In conclusion, neither a brief
      computer-based nor targeted health coaching intervention reduced patients' viral
      loads beyond levels achieved with standard of care services available to patients
      at well-resourced HIV clinics.

PMID- 30114937
TI  - Both mental and physical health predicts one year mortality and readmissions in
      patients with implantable cardioverter defibrillators: findings from the national
      DenHeart study.
AB  - BACKGROUND: Although highly effective in preventing arrhythmic death, there is a
      high prevalence of anxiety, depression and reduced quality of life among patients
      who have received an implantable cardioverter defibrillator (ICD). Whether
      mortality, ICD shock and readmission are predicted by patient-reported outcomes
      is unknown. AIM: The aim of this study was to describe patient-reported outcomes
      among patients with ICDs compared by: ICD indication and generator type (ICD or
      cardiac resynchronisation therapy ICD), and to determine whether patient-reported
      outcomes at discharge predict mortality, ICD therapy and readmission. METHODS: A
      national cross-sectional survey at hospital discharge ( n=998) with register
      follow-up. Patient-reported outcomes included the Hospital Anxiety and Depression
      Scale, Short Form-12, HeartQoL, EQ-5D and Edmonton Symptom Assessment Scale.
      Register data: ICD therapy, readmissions and mortality within one year following
      discharge. RESULTS: Patients with primary prevention ICDs had significantly worse
      patient-reported outcomes at discharge than patients with secondary prevention
      ICDs. Likewise, patients with cardiac resynchronisation therapy ICDs had
      significantly worse patient-reported outcomes at discharge than patients without
      cardiac resynchronisation therapy. One-year mortality was predicted by patient
      reported outcomes, with the highest hazard ratio (HR) being anxiety (HR 2.02;
      1.06-3.86), but was not predicted by indication or cardiac resynchronisation
      therapy. ICD therapy and ventricular tachycardia/ventricular fibrillation were
      not predicted by patient-reported outcomes, indication or cardiac
      resynchronisation therapy. Overall, patient-reported outcomes predicted
      readmissions, e.g. symptoms of anxiety and depression predicted all readmissions
      within 3 months (HR 1.50; 1.13-1.98) and 1.47 (1.07-2.03), respectively).
      CONCLUSION: Patients with primary indication ICDs and cardiac resynchronisation
      therapy ICDs report worse patient-reported outcomes than patients with secondary
      indication and no cardiac resynchronisation therapy. Patient-reported outcomes
      such as mental health, quality of life and symptom burden predict one-year
      mortality and acute and planned hospital readmissions.

PMID- 30114938
TI  - Effective diversity, equity, and inclusion practices.
AB  - Demographics in Canada, and the workplace, are changing. These include population
      changes due to race, ethnicity, religion/faith, immigration status, gender,
      sexual identity and orientation, disability, income, educational background,
      socioeconomic status, and literacy. While this rich diversity can present
      challenges for patient experiences/outcomes and working environments, it can also
      present opportunities for positive transformation. For successful transformation
      to take place, strategies should focus on "Diversity, Equity, and Inclusion"
      (DEI) versus "diversity" alone and on creating inclusive team environments for
      positive staff experiences/engagement. There is a growing understanding of the
      relationship between the providers' work environments, patient outcomes, and
      organizational performance. This article leverages the principle of improving the
      healthcare provider's experience based on Health Quality Ontario's Quadruple Aim
      ("people caring for people"). Based on learnings/experiences, the top three
      successful practices from the organization's DEI strategy have been outlined in
      this article.

PMID- 30114939
TI  - Exploring the costs of a 13-valent pneumococcal conjugate vaccination program for
      home care patients.
AB  - OBJECTIVE: The city of Joensuu in Finland vaccinated 409 elderly home care
      patients with the 13-valent pneumococcal conjugate vaccine (PCV13) in autumn
      2012. All home care patients were also eligible for a seasonal influenza vaccine.
      The objective of this retrospective real-world data cohort study was to evaluate
      whether the immunization intervention with PCV13 for home care patients was cost
      saving from the payer's (municipality's) perspective in terms of a return on
      investment (ROI). METHODS: This was a retrospective observational registry study.
      We used registry data from the regional Mediatri patient information system
      covering all North Karelian municipalities, including individual-level data for
      all health and social care service utilization, diagnoses and procedures. Home
      care patients and their use of services were followed for 2 years. Cost
      comparisons were based on two specifications: (1) pneumonia-related health care
      costs; and (2) total health care costs. We compared patients who had received
      both influenza and PCV13 vaccinations to patients only vaccinated against
      influenza. RESULT: The pneumonia-related costs in the PCV13-vaccinated group were
      434 EUR lower and the total health care costs 3800 EUR lower per person, compared
      to the non-PCV13-vaccinated group (bootstrapped 95% CIs -1682-527 EUR and -8233
      621 EUR, respectively). PCV13 vaccination was associated with a return on
      investment of 7 EUR per 1 EUR spent during the 2 year follow-up period when
      pneumonia-related costs were used as baseline. Probability of the positive return
      on investment was .715. CONCLUSION: The results suggest that vaccinating home
      care patients could potentially be cost saving from the health care and service
      producer's perspectives. The uncertainty from the decision-making perspective was
      due to the large variation in individual costs.

PMID- 30114940
TI  - Responsiveness: is it time to move beyond ordinal scores and approach interval
      measurements?

PMID- 30114941
TI  - Progressive Massive Fibrosis Resurgence Identified in U.S. Coal Miners Filing for
      Black Lung Benefits, 1970-2016.
AB  - RATIONALE: There has been a resurgence of progressive massive fibrosis (PMF) in
      the United States, particularly among central Appalachian miners. OBJECTIVES: We
      characterized the proportion of PMF among former U.S. coal miners applying for
      Federal Black Lung Program benefits, 1970-2016. METHODS: Data from the U.S.
      Department of Labor were used to characterize trends in proportion of PMF cases,
      defined as an approved black lung claim with a determination of PMF, among all
      miners who filed for federal benefits between January 1, 1970, and December 31,
      2016. Joinpoint, logistic, and linear regression models were used to identify
      changes in the proportion of claimants with PMF over time. RESULTS: There were
      4,679 unique PMF cases among claimants for federal black lung benefits between
      1970 and 2016, with 2,474 miners determined to have PMF since 1996. The number of
      PMF cases among Federal Black Lung Program claimants fell from 404 (0.5% of
      claimants) in 1978 to a low of 18 cases (0.6%) in 1988, and then increased to 353
      cases (8.3%) in 2014. The proportion of federal black lung benefits claimants
      with PMF has been increasing since 1978 (0.06% annual percent change [APC]; 95%
      confidence interval [CI], 0.05-0.07%; P < 0.0001), and began increasing at a
      significantly increased rate after 1996 (0.26% APC; 95% CI, 0.25-0.28%; P <
      0.0001). Most miners with PMF (84%) last mined in West Virginia, Kentucky,
      Pennsylvania, or Virginia. Since 1970, the proportion of claimants with PMF has
      increased significantly among miners who last worked in Kentucky (16.6% APC; 95%
      CI, 16.5-16.7%), Pennsylvania (4.7% APC; 95% CI, 4.6-4.8%), Tennessee (16.1% APC;
      95% CI, 15.7-16.4%), West Virginia (16.8% APC; 95% CI, 16.6-16.9%), and most
      sharply among miners last working in Virginia (31.5% APC; 95% CI, 31.2-31.7%),
      where in 2009, more than 17% of claimants received a PMF determination. The
      proportion of PMF determinations for the rest of the United States has not
      exceeded 4%. CONCLUSIONS: There has been a resurgence of PMF, particularly in
      central Appalachian miners. The resurgence of this preventable disease points to
      the need for improved primary and secondary prevention of dust-related lung
      disease in U.S. coal miners.

PMID- 30114942
TI  - Serum Electrolyte Levels and Ventricular Arrhythmia.

PMID- 30114943
TI  - Benefit-risk review of different drug classes used in chronic heart failure.
AB  - INTRODUCTION: Heart failure (HF) is an important public health problem with an
      increasing prevalence across the globe. The mortality rates from this complex
      clinical problem have stabilized in the recent years with the use of
      pharmacotherapeutics which demonstrated survival benefits in patients with HF
      with reduced ejection fraction (HFrEF). Areas covered: We reviewed the seven
      classes of medications which constitute the guideline-directed medical therapy
      (GDMT) in chronic HF patients. We discussed clinical trials which support or
      contradict their use, potential adverse events, and available real-world data on
      utilization and safety. Expert opinion: Loop diuretics form a major component of
      baseline therapy in HF patients to maintain euvolemia. As diastolic HF is more
      volume sensitive then systolic HF, diuretic use should be judiciously monitored
      to prevent states of volume depletion and associated complications. Neurohormonal
      modulation with pharmacotherapies are efficacious in reducing morbidity and
      mortality in the chronic HFrEF population. However, registry data showed that
      treatment intolerance and adverse events result in lower prescription rates of
      GDMT. Sacubitril/valsartan represents a major therapeutic advance in the
      treatment of HFrEF patients and can be safely used in addition to other GDMTs.
      Therapies to improve outcomes in diastolic HF  patients are needed.

PMID- 30114944
TI  - Prevalence of Preventive and Symptomatic Drug Treatments in Hospice Care: An
      Italian Observational Study.
AB  - BACKGROUND: The aim of pharmacotherapy in people at the end of life should be
      symptom control, more than prolonging life. Drugs for disease prevention should
      therefore be discouraged, but this is not the usual practice. The prevalence of
      unnecessary preventive drugs at the end of life is not well described, although
      some studies suggest it is common. METHODS: This retrospective longitudinal study
      describes the prevalence of patients receiving preventive and symptomatic drug
      treatments at admission (T1) and before death (T2) in an Italian hospice. All
      adults admitted to the VIDAS hospice between March 2015 and February 2017 were
      included in the analysis. RESULTS: The study sample comprised 589 end-of-life
      patients with a mean age of 75.3 (12.1) years. The mean number of drugs decreased
      from admission to the hospice to the time of death (mean [standard deviation]:
      9.7 [3.4] and 8.7 [3.0]). All patients were appropriately treated with
      symptomatic drugs at T1 and T2, while there were significantly fewer patients
      from T1 to T2 with at least 1 preventive medication that could be considered for
      deprescription at the end of life (511, 86.8% and 286, 48.6%; P < .0001).
      CONCLUSIONS: Hospice admission can be associated with a definite reduction in the
      use of commonly prescribed preventive medications. However, about half of end-of
      life patients can be prescribed avoidable medications. Drugs for peptic ulcer and
      gastroesophageal reflux disease and antithrombotics were the potentially
      avoidable preventive medications most frequently prescribed at admission to the
      hospice and before death.

PMID- 30114945
TI  - Home-based family focused rehabilitation for adolescents with severe Chronic
      Fatigue Syndrome.
AB  - AIMS: The purpose of this article is to describe and evaluate a home based,
      family focused rehabilitative approach for severely affected housebound
      adolescents with Chronic Fatigue Syndrome (CFS). The main aims were to facilitate
      a return to school, improve physical functioning, reduce fatigue and assess any
      adverse effects of the intervention. METHODS: Six housebound adolescents aged 11
      18, diagnosed with CFS by a paediatrician, were assessed and treated at home by
      an experienced cognitive behaviour therapist. Outcomes were assessed 12 months
      after discharge from treatment. RESULTS: At 12 months follow-up all patients had
      returned to either school or college, and physical functioning had improved in
      most of the patients. Fatigue had reduced in some. No adverse effects of the
      intervention were reported. CONCLUSION: Severely affected adolescents with CFS
      showed improved physical functioning and social adjustment after a home-based
      rehabilitative approach. Although several patients showed improvements in
      physical functioning, they did not all show substantial improvements in fatigue.
      At this crucial stage of development, it is important to offer young people and
      their parents hope by stating that improvement is possible.

PMID- 30114946
TI  - All the players in the game: driving home the global commitment for legitimate
      drugs.
AB  - Substandard, falsified, and counterfeit medications are a concern for the
      industry and for the public's health. Data collection and research on these
      illegitimate drugs must continue to be a priority and common recommendations must
      be implemented immediately. The health of the public continues to be at risk, and
      as such global consensus and collaboration must be swift. Process improvements
      and policy decisions can support expert recommendations while technology and
      research continue to drive home change. Addressing counterfeit and substandard
      drugs is cost effective, feasible, and the right thing to do.

PMID- 30114947
TI  - Comparison of Ankle Pressure, Systolic Toe Pressure, and Transcutaneous Oxygen
      Pressure to Predict Major Amputation After 1 Year in the COPART Cohort.
AB  - The hemodynamic definition of critical limb ischemia (CLI) has evolved over time
      but remains controversial. We compared the prediction of major amputation by 3
      hemodynamic methods. Patients were selected from the Cohorte des Patients
      ARTeriopathes cohort of patients hospitalized for peripheral arterial disease.
      Patients with CLI were enrolled according to the Trans-Atlantic Inter-Society
      Consensus Document on Management of Peripheral Arterial Disease II definition and
      followed up for at least 1 year. We compared the major amputation rate according
      to initial ankle pressure (AP), systolic toe pressure (STP), and forefoot
      transcutaneous oxygen pressure (TcPO2); 556 patients were included and divided
      into surgical (264) and medical (292) groups. The AP failed to identify 42% of
      patients with CLI. After 1 year, 27% of medical and 17% of surgical patients had
      undergone major amputation. The TP <30 mm Hg predicted major amputation in the
      whole sample and in the medical group (odds ratio [OR] 3.5 [1.7-7.1] and OR 5 [2
      12.4], respectively), but AP did not. The TcPO2 <10 mm Hg also predicted major
      amputation (OR 2.3 [1.5-3.5] and OR 3.8 [2.1-6.8]). The best predictive
      thresholds to predict major amputation were STP <30 mm Hg and TcPO2 <10 mm Hg.
      None of these methods performed before surgery was able to predict outcome in the
      revascularized patients.

PMID- 30114948
TI  - Coronary Artery Disease Severity Is Associated With Abdominal Aortic Intima-Media
      Thickness in Patients With Non-ST-Segment Elevation Myocardial Infarction.
AB  - The aim of this study was to evaluate the relationship between aortic intima
      media thickness (aIMT) and coronary artery disease (CAD) severity in patients
      with non-ST-segment elevation myocardial infarction (NSTEMI). SYNTAX score (SS)
      was calculated. Patients were categorized into 2 main groups according to the SS:
      patient with high risk (SS >= 13) and low risk (SS < 13). Common carotid artery
      IMT (cIMT), common femoral artery IMT, and aIMT were measured with a high
      resolution ultrasound Doppler system. We had 147 (52.9%) patients in the high
      risk group and 132 patients in the low-risk group. Both cIMT and aIMT were
      significantly increased, and left ventricular ejection fraction (LVEF) was
      significantly lower in the high-risk group; aIMT (odds ratio [OR]: 1.272, P <
      .001), cIMT (OR: 1.239, P = .009), and LVEF (OR: 0.931, P = .002) were determined
      as independent predictors for the high-risk group. When the cutoff value was
      accepted as 1.25 mm for the aIMT, patients with high SS identification had 74.1%
      sensitivity and 89.4% specificity (area under the curve: 0.764, P < .001). In
      conclusion, aIMT detected by abdominal B-mode ultrasonography is closely
      associated with CAD severity in patients with NSTEMI.

PMID- 30114949
TI  - Glucose Concentration Affects Fibrin Clot Structure and Morphology as Evidenced
      by Fluorescence Imaging and Molecular Simulations.
AB  - Although in vivo studies have been conducted in the past to determine
      hyperglycemic effects and influence on clotting risk in patients with diabetes,
      the true extent of hyperglycemia on unstable and spontaneous clot formation
      remains highly debated. Factors such as increased glycation, elevated fibrinogen
      concentration, elevated prothrombin levels, and decreased plasminogen are known
      to influence fibrin conversion, clot morphology, and thrombus formation in these
      individuals. In this regard, the isolated effects of hyperglycemia on irregular
      fibrin clot formation were investigated in a controlled fibrinogen system. In
      this study, fibrin clot characteristic differences at 3 glucose concentrations
      were analyzed to determine the effects of glucose concentration on fibrinogen
      glycation and fibrin clot morphology using confocal microscopy, glycation
      quantification, molecular simulations, and image processing methods. Algorithms
      coupled with statistical analysis support in vivo findings that hyperglycemia
      increases fibrinogen glycation, with ensuing altered fibrin clot structure
      characteristics. Our experimental and molecular simulation results consistently
      show an increased glucose adsorption by fibrinogen with increased glucose
      concentration. Significant differences in clot structure characteristics were
      observed, and the results of this work can be used to further develop diagnostic
      tools for evaluating clotting risk in individuals with hypercoagulable and
      hyperglycemic conditions.

PMID- 30114950
TI  - The Impact of co-morbid severe mental illness and HIV upon mental and physical
      health and social outcomes: a systematic review.
AB  - Our aim was to review the evidence related to the impact of co-morbid severe
      mental illness SMI (schizophrenia, schizoaffective and bipolar disorder) and HIV
      upon mental health, physical health and social outcomes. We carried out a
      systematic review of scientific evidence, searching online databases (MEDLINE,
      PsychInfo, EMBASE, Global Health and Scopus) for studies between 1983 and 2017
      using search terms for SMI and HIV. Studies were included if they compared health
      or social outcomes between people living with co-morbid SMI and HIV and people
      living with either: a) HIV only; or b) SMI only. Outcomes of interest were:
      mortality, health service use, HIV/SMI-related, co-morbidities, and social
      outcomes. We identified 20 studies which met our inclusion criteria. Although
      studies were generally high quality, there was heterogeneity in both selection of
      outcomes and choice of measure. It was therefore difficult to draw strong
      conclusions regarding the impact of co-morbid SMI and HIV across any outcome. We
      found little evidence that co-morbid SMI and HIV were associated with lower
      levels of treatment, care or poorer clinical outcomes compared to people living
      with SMI or HIV alone. However, mortality appeared to be higher among the co
      morbid group in three out of four analyses identified. Physical and mental co
      morbidities and social outcomes were rarely measured. Limited data mean that the
      impact of co-morbid SMI and HIV is uncertain. In order to develop evidence-based
      guidelines, there is an urgent need for further research. This may be realized by
      exploring opportunities for using data from existing cohort studies, routinely
      collected data and data linkage to investigate important questions relating to
      this neglected but potentially important area.

PMID- 30114951
TI  - Aerosol source (biomass, traffic and coal emission) apportionment in Lithuania
      using stable carbon and radiocarbon analysis.
AB  - In the present study, a combination of the stable carbon isotope ratio (13C/12C)
      with radiocarbon data (14C) allowed us to perform the aerosol source
      apportionment. Filter samples of PM1 were collected during the warm and cold
      periods in rural and urban sites in Lithuania. The 14C/12C ratio of total carbon
      (TC) was measured using the single stage accelerator mass spectrometer
      quantifying of fossil and non-fossil derived aerosol emissions. The delta13C
      value was measured using an elemental analyser interfaced with an isotope ratio
      mass spectrometer. We have found that the highest fraction of contemporary carbon
      (fc = 0.82) was measured during a warm period in a rural location. A higher
      fraction of fossil fuel-derived carbon was observed for air masses transported
      from highly industrialized Western European regions during both seasons. Isotope
      mass balance calculations revealed that the traffic emissions composed 15 and 25
      % in rural and urban sites, respectively, and did not change during either
      season. Input from coal-derived aerosol particles was estimated to be 15 % at an
      urban site during the cold period. The combination of the stable carbon isotope
      ratio with the radiocarbon data allowed us to distinguish coal, liquid fossil
      fuel combustion, and non-fossil derived aerosol particle emissions.

PMID- 30114953
TI  - Combination therapy of hepatocellular carcinoma by DNA shuffling-based VEGF
      vaccine and doxorubicin.
AB  - Antiangiogenic therapy can enhance the efficacy of chemotherapy against solid
      tumors. This study was to determine whether TT46, a potential VEGF vaccine from
      DNA shuffling with a helper T-cell epitope of tetanus toxin B subunit, could
      enhance the efficacy of doxorubicin to combat hepatocellular carcinoma (HCC).
      Compared with monotherapy, the combination with TT46 vaccination and doxorubicin
      could significantly reduce microvessel counts and inhibit tumor angiogenesis.
      Enhanced immunization with TT46 for total six doses could induce long-term
      response maintenance with high anti-VEGF antibody titers in body. As a result,
      the combination with enhanced TT46 vaccination and doxorubicin significantly
      inhibited the HCC growth, and improved the survival rate of HCC-bearing mice in
      both of subcutaneous tumor model and lung metastasis model. In conclusion, the
      combined therapy with TT46 vaccination and doxorubicin has antitumor effects in
      both a prophylactic and therapeutic setting in a mouse model of H22
      hepatocellular carcinoma.

PMID- 30114952
TI  - Analysis of peripheral blood lymphocyte subsets in critical patients at ICU
      admission: A preliminary investigation of their role in the prediction of sepsis
      during ICU stay.
AB  - A better knowledge of factors predicting the development of sepsis in patients
      hospitalized in intensive care unit (ICU) might help deploy more targeted
      preventive and therapeutic strategies. In addition to the known clinical and
      demographic predictors of septic syndromes, in this study, we investigated
      whether measuring T and B lymphocyte subsets upon admission in the ICU may help
      individualize the prediction of ensuing sepsis during ICU stay. Between May 2015
      and December 2016, we performed a prospective cohort study evaluating peripheral
      blood lymphocyte T-CD4+ (T-helper cells), T-CD8+ (cytotoxic T-cells), T-CD56 +
      (natural killer cells), and T-CD19+ (B-lymphocytes), using flow cytometry on
      blood samples collected 2 days after admission in the ICU. We enrolled 176
      patients, 65.3% males, with mean age of 61.1 +/- 15.4 years. At univariate
      analyses, higher percentages of CD19 B-cells were significantly associated with
      ensuing sepsis (20.5% (15.7-27.7)% vs 16.9% (11.3-22)%, P = 0.0001), whereas
      median interquartile range (IQR) proportions of CD4 T-cells (41.2% (33.4-50.6)%
      vs 40% (35-47)%, P = 0.5), CD8 T-cells (21.1% (15.8-28.2)% vs 19.6% (14.6-25.1)%,
      P = 0.2) and CD56 T-cells (1.7% (0.9-3.1)% vs 1.45% (0.7-2.3)%, P = 0.4) did not
      reveal any significant association. An unexpected, highly significant inverse
      correlation of CD8 T-cells and CD19 B-cells proportions, however, was observed,
      suggesting that patients with lower CD19 and higher CD8 proportions might be
      somehow protected from ensuing sepsis. We therefore studied the ability of the
      CD8/CD19 ratio to predict ensuing sepsis in our sample. In final models of
      multivariate logistic regression, the following independent associations were
      found: previous antibiotic exposure (odds ratio (OR): 3.8 (95% confidence
      interval (CI): 1.35-10.87), P = 0.01), isolation of at least one multi-drug
      resistant organism at any time during ICU stay (OR: 8.4 (95% CI: 3.47-20.6), P <
      0.0001), decreasing age (OR: 0.9 (95% CI: 0.93-0.99), P = 0.02) and a CD8/CD19
      ratio >2.2 (OR: 10.3 (95% CI: 1.91-55.36), P = 0.007). Our data provide
      preliminary evidence that immune characterization of critically ill patients on
      ICU admission may help personalize the prediction of ensuing sepsis during their
      ICU stay. Further polycentric evaluation of the true potential of this new tool
      is warranted.

PMID- 30114954
TI  - Long-term cost-effectiveness analysis shows that IDegLira is associated with
      improved outcomes and lower costs compared with insulin glargine U100 plus
      insulin aspart in the US.
AB  - AIMS: The clinical and economic impact of diabetes is growing in the US. Choosing
      therapies that are both effective and cost-effective is becoming increasingly
      important. The aim of the present analysis was to assess the long-term cost
      effectiveness of IDegLira for treatment of patients with type 2 diabetes mellitus
      not meeting glycemic targets on basal insulin, vs insulin glargine U100 plus
      insulin aspart, in the US setting. MATERIALS AND METHODS: Long-term projections
      of cost-effectiveness outcomes were made using the IQVIA CORE Diabetes Model.
      Clinical inputs were based on the DUAL VII trial, with costs (accounted from a
      healthcare payer perspective) and utilities based on published sources. Future
      costs and clinical benefits were discounted at 3% annually. RESULTS: IDegLira was
      associated with increased discounted life expectancy by 0.02 years and increased
      discounted quality-adjusted life expectancy by 0.22 quality-adjusted life years
      compared with insulin glargine U100 plus insulin aspart. Evaluation of direct
      medical costs suggested that the mean cost per patient with IDegLira was $3,571
      lower than with insulin glargine U100 plus insulin aspart. The cost saving was
      driven predominantly by the lower acquisition cost of IDegLira compared with
      insulin glargine U100 plus insulin aspart, with further cost savings identified
      as a result of avoided treatment of diabetes-related complications. IDegLira was
      associated with improved clinical outcomes at a reduced cost compared with
      insulin glargine U100 plus insulin aspart. CONCLUSIONS: Based on clinical trial
      data, the present analysis suggests that IDegLira is associated with improved
      clinical outcomes and cost savings compared with treatment with insulin glargine
      U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic
      control on basal insulin in the US. Therefore, IDegLira is likely to be
      considered dominant (cost saving and more effective) and, consequently, highly
      cost-effective in the US setting.

PMID- 30114956
TI  - Shared decision making can aid the informed consent process for end-of-life
      chemotherapy in cancer patients.

PMID- 30114955
TI  - Ten guidelines for the design of non-assembly mechanisms: The case of 3D-printed
      prosthetic hands.
AB  - In developing countries, prosthetic workshops are limited, difficult to reach, or
      even non-existent. Especially, fabrication of active, multi-articulated, and
      personalized hand prosthetic devices is often seen as a time-consuming and
      demanding process. An active prosthetic hand made through the fused deposition
      modelling technology and fully assembled right after the end of the 3D printing
      process will increase accessibility of prosthetic devices by reducing or
      bypassing the current manufacturing and post-processing steps. In this study, an
      approach for producing active hand prosthesis that could be fabricated fully
      assembled by fused deposition modelling technology is developed. By presenting a
      successful case of non-assembly 3D printing, this article defines a list of
      design considerations that should be followed in order to achieve fully
      functional non-assembly devices. Ten design considerations for additive
      manufacturing of non-assembly mechanisms have been proposed and a design case has
      been successfully addressed resulting in a fully functional prosthetic hand. The
      hand prosthesis can be 3D printed with an inexpensive fused deposition modelling
      machine and is capable of performing different types of grasping. The activation
      force required to start a pinch grasp, the energy required for closing, and the
      overall mass are significantly lower than body-powered commercial prosthetic
      hands. The results suggest that this non-assembly design may be a good
      alternative for amputees in developing countries.

PMID- 30114957
TI  - The patient's voice in the emerging era of participatory medicine.
AB  - Professionalism in any field requires keeping pace with change, and nowhere is it
      more true than medicine. Knowledge flow has changed dramatically since today's
      accreditation standards were developed, and change continues more rapidly than
      ever. It's time for a fresh look at how best to achieve care in this altered
      environment, where valid knowledge may come from the patient as well as from
      clinician resources: a sociological change driven by technological change. The
      power structure of the clinical relationship is inevitably altered as constraints
      on patient knowledge are loosened by the internet, apps, and devices, undermining
      a paradigm of patients as uninformed recipients of care based on a one-way flow
      of wisdom from providers. Case after case is presented showing that patients
      today have generated undeniable value, violating the expectations and assumed
      best practices of the old model. To understand this sociological (yet scientific)
      change, this article reviews the role of paradigms in the history of sciences as
      described in Thomas Kuhn's landmark book The Structure of Scientific Revolutions
      and describes how these anomalous patient stories force the conclusion that the
      traditional paradigm of patients is no longer supportable and a new paradigm is
      needed. This in turn means our standards of professionalism and appropriate care
      must be updated, lest we fail to achieve best possible care in our increasingly
      overburdened system. Our new standard must be to teach clinicians to recognize,
      welcome, and work with empowered "e-patients" in the new model of participatory
      medicine.

PMID- 30114958
TI  - A positive psychology-motivational interviewing intervention for patients with
      type 2 diabetes: Proof-of-concept trial.
AB  - Objective Eighteen million Americans with type 2 diabetes (T2D) do not follow
      recommended guidelines for physical activity. Motivational interviewing (MI) has
      had modest effects on activity and related behaviors in T2D. Positive
      psychological attributes (e.g., optimism) are associated with superior medical
      outcomes in T2D, and positive psychology (PP) interventions promote such
      attributes. There had been no study in T2D of a combined PP-MI intervention to
      promote well-being and health behavior adherence. We developed a novel, telephone
      delivered, 16-week PP-MI intervention and explored its feasibility and impact in
      T2D patients in a single-arm, proof-of-concept trial. Method Participants
      completed PP-based exercises and MI-based physical activity goal-setting
      activities and reviewed these activities weekly with a study trainer for 16
      weeks. Feasibility and acceptability were assessed via exercise completion rates
      and post-exercise ratings of ease/utility (0-10 scales). Impact was explored by
      examining changes in physical activity (via accelerometers and self-report),
      other health behaviors, psychological measures, and medical outcomes (e.g.,
      hemoglobin A1c (A1C)) from baseline to 16 weeks, using paired t tests. Results
      Twelve participants enrolled, and 10 provided follow-up data. Seventy-eight
      percent of PP-MI activities were completed, and participants rated the PP-MI
      content and sessions as easy (mean = 8.2/10, standard deviation (SD) = 1.9) and
      useful (mean = 9.1/10, SD = 1.5). PP-MI was associated with improved adherence to
      health behaviors and overall self-care, variable effects on accelerometer
      measured activity and psychological outcomes, and modest beneficial effects on
      body mass index and A1C. Conclusion Further testing of this intervention is
      warranted in a larger, controlled trial to assess its effects on important health
      outcomes.

PMID- 30114960
TI  - Cardiopulmonary bypass prime composition: beyond crystalloids versus colloids.
AB  - INTRODUCTION: In the literature addressing cardiopulmonary bypass (CPB) prime
      composition, there is a considerable lack of discussion concerning plasma
      osmolality changes induced by using a hyperosmolar prime. With this study, we try
      to determine the magnitude and temporal relationship of plasma osmolality changes
      related to the use of a hyperosmolar CPB prime. METHOD: In this prospective
      observational study performed in a university hospital setting, we enrolled
      thirty patients scheduled for elective coronary bypass surgery. Plasma osmolality
      was analysed on eight occasions. A hyperosmolar CPB prime was used. RESULTS:
      Analyses of the perioperative plasma osmolality on eight occasions gave the
      following results: the preoperative osmolality level was normal (297+/-4
      mOsm/kg); a significant increase to 322+/-17 mOsm/kg (p<0.001) was observed at
      the commencement of CPB and remained elevated after 30 minutes (310+/-4 mOsm/kg)
      and throughout the procedure (309+/-4 mOsm/kg); the osmolality level returned to
      291+/-5 mOsm/kg on day 1 postoperatively and remained normal the following day
      (291+/-6 mOsm/kg). CONCLUSIONS: Use of hyperosmolar CPB prime resulted in a
      dramatic and instant elevation of the plasma osmolality. Rapid changes in plasma
      osmolality are associated with organ dysfunction (e.g. osmotic demyelination
      syndrome), therefore, effects on plasma osmolality related to the CPB prime
      composition should be recognised. Influence on organ function and clinical
      outcome warrants further investigations. - Clinical Trials.gov (NCT03060824).
      Changes in Plasma Osmolality Related to the Use of Cardiopulmonary Bypass With
      Hyperosmolar Prime. URL:
      https://clinicaltrials.gov/ct2/show/NCT03060824?term=cpb&cond=osmolality&rank=1.

PMID- 30114959
TI  - A percutaneous, minimally invasive annulus fibrosus needle puncture model of
      intervertebral disc degeneration in rabbits.
AB  - PURPOSE: Various animal models have been proposed to mimic the pathophysiologic
      process of intervertebral disc degeneration, a leading cause of back pain. The
      purpose of this study is to describe a minimally invasive technique via
      percutaneous needle puncture of the annulus fibrosus in New Zealand white
      rabbits. METHODS: Under fluoroscopic guidance, an 18-gauge spinal needle was
      inserted 2 cm lateral to the midline spinous process. The needle was slowly
      advanced at approximately 45 degrees  angle until it was adjacent to the L5/L6
      disc space. Lateral and anteroposterior views were used to verify correct needle
      position before advancing into the nucleus pulposus. The rabbits underwent weekly
      X-rays for 4 weeks to assess disc height index. MRI T2 relaxation was evaluated
      at week four to assess morphological changes. Discs were histologically graded on
      a 12-point scale to assess degeneration and compared to discs obtained from
      uninjured rabbits. RESULTS: There were no complications associated with the
      percutaneous needle puncture procedure. All animals survived the duration of the
      experiment. Four weeks after injury, the disc height had progressively narrowed
      to approximately 50% of baseline. MRI assessment at the 4-week time point
      demonstrated a mean T2 relaxation time at the L5/L6 level that was 20.9% of the
      T2 relaxation time at the uninjured L4/L5 disc level ( p < 0.001). Histological
      analysis demonstrated lamellar disorganization of the annulus and decreased
      cellularity and proteoglycan content within the injured nucleus compared to
      uninjured control discs. CONCLUSION: The present study demonstrated a reliable
      technique of inducing an annular tear via a percutaneous needle puncture.
      Compared to open surgical approaches, the percutaneous model produces similar
      progressive disc degeneration while minimizing harm to the animal subjects.
      CLINICAL RELEVANCE: The present study establishes a technique for the
      introduction of novel therapeutic agents to treat disc degeneration that may
      translate to future clinical trials.

PMID- 30114961
TI  - Sixty years of change in Tibetan fertility: An assessment.
AB  - Existing knowledge of Tibetan historical population development is mostly based
      on 'best-guess' estimates and is heavily politicized. Using census data, I
      reconstruct the development of Tibetan fertility in China since the 1940s, with
      the objective of providing an independent assessment that can be used as
      benchmark for future studies and debates on Tibetan demography. Following major
      social and economic transformations starting in the 1950s, Tibetan fertility
      unexpectedly increased from the late 1950s to the late 1960s. As noted in several
      existing studies, Tibetan fertility in China then declined swiftly from the early
      1980s onwards and has now reached values close to replacement level. Focusing on
      the 1950-70 period, I examine factors that contributed to shaping the Tibetan
      fertility increase in more detail. This confirms that changes in nuptiality and
      disease-related infertility both played a role in pushing up fertility rates
      among Tibetan women in China.

PMID- 30114963
TI  - Conflating screening detection rates with the uptake of further testing: A
      potential source of confusion.

PMID- 30114962
TI  - Kallikrein-related peptidases represent attractive therapeutic targets for
      ovarian cancer.
AB  - INTRODUCTION: Aberrant levels of kallikrein-related peptidases (KLK1-15) have
      been linked to cancer cell proliferation, invasion and metastasis. In ovarian
      cancer, the KLK proteolytic network has a crucial role in the tissue and tumor
      microenvironment. Publically available ovarian cancer genome and expression data
      from multiple patient cohorts show an upregulation of most KLKs. Areas covered:
      Here, we review the expression levels of all 15 members of this family in normal
      and ovarian cancer tissues, categorizing them into highly and moderately or
      weakly expressed KLKs, and their association with patient prognosis and survival.
      We summarize their tumor-biological functions determined in cell-based assays and
      xenograft models, further highlighting their suitability as cancer biomarkers and
      attractive candidates for drug development. Finally, we discuss some different
      pharmaceutical approaches, including peptide-based and small molecule inhibitors,
      cyclic peptides, depsipeptides, engineered natural inhibitors, antibodies,
      RNA/DNA-based aptamers, prodrugs, miRNA and siRNA. Expert opinion: In light of
      the results from clinical and tumor-biological studies, together with the
      available pharmaceutical tools, we suggest KLK4, KLK5, KLK6 and possibly KLK7 as
      preferred targets for inhibition in ovarian cancer.

PMID- 30114964
TI  - Navigation of a 6-French guiding sheath into the common carotid artery using a
      tri-axial catheter system in transbrachial carotid artery stenting.
AB  - Background and purpose Placement of a large-bore guiding sheath or catheter into
      the common carotid artery (CCA) is crucial in transbrachial carotid artery
      stenting (CAS). Herein, we describe technical tips for the navigation of a 6
      French guiding sheath into the CCA using a tri-axial catheter system in
      transbrachial CAS. Materials and methods A total of 27 patients underwent
      transbrachial CAS. For the right side, a 6-French straight guiding sheath was
      navigated directly into the CCA using a tri-axial catheter system, with a 4
      French Simmons catheter placed through a 6-French straight guiding catheter. For
      the left side, a 6-French Simmons guiding sheath was navigated into the CCA using
      a tri-axial catheter system, with a 4-French Simmons catheter placed through a 6
      French Simmons guiding catheter. After the placement of a 6-French guiding sheath
      into the CCA, CAS was performed under distal filter or balloon protection.
      Results Fifteen patients had a right carotid stenosis and 12 patients had a left
      carotid stenosis. The 6-French guiding sheath was safely placed with ease and
      provided adequate stabilization for CAS. All procedures were successfully
      performed without any complications. Conclusion The use of a tri-axial catheter
      system for the navigation of a 6-French guiding sheath into the CCA appears safe
      and efficient, allowing transbrachial CAS, with 6-French guiding sheath
      stabilization, to be performed without any complication.

PMID- 30114965
TI  - Structure based virtual screening, 3D-QSAR, Molecular dynamics and ADMET studies
      for selection of natural inhibitors against structural and non-structural targets
      of Chikungunya.
AB  - The transmission of mosquito-borne Chikungunya virus (CHIKV) has large epidemics
      worldwide. Till date, there are neither anti-viral drugs nor vaccines available
      for the treatment of Chikungunya. Accumulated evidences suggest that some natural
      compounds i.e. Epigallocatechin gallate, Harringtonine, Apigenin, Chrysin,
      Silybin etc. have the capability to inhibit CHIKV replication in vitro. Natural
      compounds are known to possess less or no side effects. Therefore, natural
      compound in its purified or crude extracts form could be the preeminent and safe
      mode of therapies for Chikungunya. Wet lab screening and identification of
      natural compounds against Chikungunya targets is a time consuming and expensive
      exercise. In the present study, we used in silico techniques like receptor-ligand
      docking, Molecular dynamic (MD), 3D-QSAR and ADME properties to screen out
      potential compounds. Aim of the study is to identify potential lead/s from
      natural sources using in silico techniques that can be developed as a drug like
      molecule against Chikungunya infection and replication. Three softwares were used
      for molecular docking studies. Potential ligands selected by docking studies were
      subsequently subjected 3D-QSAR studies to predict biological activity. Based on
      docking scores and pIC50 value, potential anti-Chikungunya compounds were
      identified. Best docked receptor-ligands were also subjected to MD for more
      accurate estimation. Lipinski's rule and ADME studies of the identified compounds
      were also studied to assess their drug likeness properties. Results of in silico
      findings, led to identification of few best fit compounds of natural origin
      against targets of Chikungunya virus which may lead to discovery of new drugs for
      Chikungunya.

PMID- 30114966
TI  - Compensation Appraisals and Labor Union Membership.
AB  - Given the beneficial effects of labor unions on "bread and butter issues," union
      members should appraise their economic circumstances more favorably than nonunion
      members do. Yet, research on the anomaly of the dissatisfied union worker
      challenges this expectation. Using the General Social Survey's Quality of Work
      Life module, this article examines whether union members appraise their economic
      circumstances less favorably than nonunion members. Results suggest that union
      membership is associated with more favorable appraisal of benefits but not wages.
      These findings may help to provide at least a partial explanation for the anomaly
      of the dissatisfied union worker. Because income constitutes a vital component of
      job satisfaction, this study contributes more broadly to our understanding of
      employee well-being. It also connects the study of occupational health to that on
      institutions, contributes to the growing literature on the political economy of
      health, and highlights latent effects of union security agreements.

PMID- 30114967
TI  - Sex differences in stroke: Challenges and opportunities.
AB  - Biologic sex influences many variables that are important to brain health in
      general, and to stroke or cerebral ischemia in particular, such as general health
      status, cerebrovascular anatomy and function, unique risk factors such as
      pregnancy and preeclampsia, symptomatology, and therapeutic response. A more
      complete understanding of the scale and depth of sexual dimorphism in the brain
      and the role of more general sex-based factors is crucial to reducing the burden
      of stroke in women and men. This focused review highlights recent findings in
      stroke, including sex differences in epidemiology, risk factor reduction,
      comparative use of stroke therapeutics in both sexes, the importance of frailty
      in women, and the biologic basis for sex differences in stroke. Such findings
      show tremendous promise for the future of personalized medicine in stroke
      prevention and treatment.

PMID- 30114968
TI  - Supramolecular complex binding to G-quadruplex DNA: Berberine encapsulated by a
      planar side arm-tethered beta-cyclodextrin.
AB  - G-quadruplex-binders have the plausible potential to act as anticancer agents.
      Herein, the mode of binding of a synthesized fluorenyl derivative of beta
      cyclodextrin with a duplex and G-quadrulex DNAs has been investigated. Moreover,
      the loading of the well-known G-quadruplex binder, berberine, in the beta
      cyclodextrin derivative using 2-dimensional rotating-frame Overhauser effect
      spectroscopy is studied. The intensity of proton NMR signals is weakened on the
      beta-cyclodextrin derivative's interaction with the quadruplexes. Binding
      constants are reported for each binding of the ligands to calf thymus DNA, kit22,
      telo24, and myc22 employing fluorescence spectroscopy. A general trend of
      fluorescence response (quenching) on the beta-cyclodextrin derivative to the DNAs
      is modified when the berberine molecule is loaded in the host structure. Despite
      berberine binds to the macromolecular target strongly, its host-guest association
      with the cavity of beta-cyclodextrin diminishes the binding strength. A
      significant difference between the binding strengths of the ligands with duplex
      and quadruplex structures is observed. Communicated by Ramaswamy H. Sarma.

PMID- 30114969
TI  - Assessing the quality, reliability and readability of online health information
      regarding systemic lupus erythematosus.
AB  - Introduction Systemic lupus erythematosus (SLE) has complex pathophysiology and
      treatments, and patients often use the internet to better understand their
      condition. This report systematically assesses the quality, reliability and
      readability of online information. Methods The search term 'systemic lupus
      erythematosus' was used with GoogleTM, BingTM and YahooTM search engines
      sequentially. The first 25 websites returned ('hits') for each search engine
      (total 75 websites) were compiled. The search terms 'SLE' and 'lupus' were used
      in separate Google searches to assess for commonality. After removal of excluded
      hits, websites were assessed using the DISCERN instrument, Journal of the
      American Medical Association benchmarks and Gunning Fog Index for quality,
      reliability and readability and presence of 'Health on the Net Code' (HoN)
      standardisation recorded. Results There was a large degree of commonality among
      hits from the three different search engines using the search term 'systemic
      lupus erythematosus', as well as hits returned for the three different search
      terms using Google. The mean DISCERN score was 47.7 (SD 13.2) for 'systemic lupus
      erythematosus', 46.4 (SD 14.2) for 'SLE' and 45.2 (SD 10.1) for 'lupus', with no
      statistically significant difference. The mean number of JAMA benchmarks (maximum
      four) present for the 'systemic lupus erythematosus', 'SLE' and 'lupus' searches
      was 1.3 (SD 1.2), 1.4 (SD 1.3) and 1.2 (SD 1.0), respectively, with no
      statistically significance difference. The average readability of hits for the
      three different search terms was 9.3 (SD 3.4), 10.0 (SD 3.1) and 11.1 (SD 2.7),
      with no statistically significant difference. Conclusion There was a large degree
      of commonality of hits among the different search engines and the utilised search
      terms but they are not synonymous. Regardless of search term, the overall quality
      of websites was fair, whilst reliability was poor. Websites appearing higher in
      searches did not score better. Presence of the HoN did not represent better
      quality. Readability was higher than recommended for near-universal
      understanding. There was no difference in quality, reliability or readability of
      websites using the search terms 'systemic lupus erythematosus', 'SLE' or 'lupus',
      with some high-scoring websites appearing in only one search term result. This
      study reminds clinicians to direct patients to high-quality websites rather than
      rely on search engines.

PMID- 30114970
TI  - Fluid dynamics in syringomyelia cavities: Effects of heart rate, CSF velocity,
      CSF velocity waveform and craniovertebral decompression.
AB  - Purpose How fluid moves during the cardiac cycle within a syrinx may affect its
      development. We measured syrinx fluid velocities before and after craniovertebral
      decompression in a patient and simulated syrinx fluid velocities for different
      heart rates, syrinx sizes and cerebrospinal fluid (CSF) flow velocities in a
      model of syringomyelia. Materials and methods With phase-contrast magnetic
      resonance we measured CSF and syrinx fluid velocities in a Chiari patient before
      and after craniovertebral decompression. With an idealized two-dimensional model
      of the subarachnoid space (SAS), cord and syrinx, we simulated fluid movement in
      the SAS and syrinx with the Navier-Stokes equations for different heart rates,
      inlet velocities and syrinx diameters. Results In the patient, fluid oscillated
      in the syrinx at 200 to 210 cycles per minute before and after craniovertebral
      decompression. Velocities peaked at 3.6 and 2.0 cm per second respectively in the
      SAS and the syrinx before surgery and at 2.7 and 1.5 cm per second after surgery.
      In the model, syrinx velocity varied between 0.91 and 12.70 cm per second.
      Increasing CSF inlet velocities from 1.56 to 4.69 cm per second increased peak
      syrinx fluid velocities in the syrinx by 151% to 299% for the three cycle rates.
      Increasing cycle rates from 60 to 120 cpm increased peak syrinx velocities by
      160% to 312% for the three inlet velocities. Peak velocities changed
      inconsistently with syrinx size. Conclusions CSF velocity, heart rate and syrinx
      diameter affect syrinx fluid velocities, but not the frequency of syrinx fluid
      oscillation. Craniovertebral decompression decreases both CSF and syrinx fluid
      velocities.

PMID- 30114972
TI  - Endovascular Repair of Ruptured Hepatic Artery Pseudoaneurysm Secondary to
      Fibromuscular Dysplasia.
AB  - We describe successful endovascular treatment of a patient with fibromuscular
      dysplasia of the celiac axis leading to development of a common hepatic artery
      pseudoaneurysm with contained rupture. An 81-year-old woman was transferred to
      our quaternary care center with concern for a hepatic artery rupture. Further
      imaging demonstrated a common hepatic artery pseudoaneurysm with surrounding
      hematoma as well as multifocal areas of narrowing and dilatation in the celiac
      trunk consistent with fibromuscular dysplasia. A similar pattern was subsequently
      identified in the bilateral renal and carotid arteries. The patient underwent
      successful endovascular exclusion of the pseudoaneurysm with a balloon-expandable
      covered stent and was discharged home without incident. Fibromuscular dysplasia
      is a nonatherosclerotic arteriopathy that can lead to stenosis, occlusion,
      dissection, and aneurysm formation. While it primarily affects the carotid and
      renal arteries, there are rare case reports involving the mesenteric vasculature.
      Endovascular therapy appears to be a feasible treatment option for the
      complicated sequelae of this condition in the rare case of mesenteric arterial
      involvement.

PMID- 30114973
TI  - Effects of low volume isometric leg press complex training at two knee angles on
      force-angle relationship and rate of force development.
AB  - This study compared knee angle-specific neuromuscular adaptations after two low
      volume isometric leg press complex training programmes performed at different
      muscle lengths. Fifteen young males were divided into two groups and trained
      three times per week for 6 weeks. One group (n = 8) performed 5-7 sets of 3 s
      maximum isometric leg press exercise, with 4 min recovery, with knee angle at 85
      degrees  +/- 2 degrees  (longer muscle-tendon unit length; L-MTU). The other
      group (n = 7) performed the same isometric training at a knee angle of 145
      degrees  +/- 2 degrees  (180 degrees  = full extension; shorter muscle-tendon
      unit length; S-MTU). During the recovery after each set of isometric exercise,
      participants performed two CMJ every minute, as a form of complex training.
      Maximum isometric force (MIF) and rate of force development (RFD) were measured
      over a wide range of knee angles. Countermovement jump (CMJ) performance and
      maximum half-squat strength (1RM) were also assessed. Training at S-MTU induced a
      large increase of MIF (22-58%, p < 0.02) and RFD (18-43%, p < 0.05 to 0.001) at
      knee angles close to the training angle and resulted in a 14 degrees  +/- 9
      degrees  shift of the force vs. knee joint angle relationship towards extended
      knee joint angles (p = 0.001). In contrast, training at L-MTU, resulted in a
      moderate and similar (~12.3%, p = 0.028) improvement of force at all knee angles.
      CMJ performance and 1RM were equally increased in both groups after training by
      10.4% +/- 8.3% and 7.8% +/- 4.7% (p < 0.001), respectively. Low-volume maximal
      isometric leg-press complex training at S-MTU causes angle-specific adaptations
      in isometric strength and RFD, while dynamic muscle performance is independent of
      muscle length during training.

PMID- 30114971
TI  - Consensus statement on placebo effects in sports and exercise: The need for
      conceptual clarity, methodological rigour, and the elucidation of neurobiological
      mechanisms.
AB  - In June 2017 a group of experts in anthropology, biology, kinesiology,
      neuroscience, physiology, and psychology convened in Canterbury, UK, to address
      questions relating to the placebo effect in sport and exercise. The event was
      supported exclusively by Quality Related (QR) funding from the Higher Education
      Funding Council for England (HEFCE). The funder did not influence the content or
      conclusions of the group. No competing interests were declared by any delegate.
      During the meeting and in follow-up correspondence, all delegates agreed the need
      to communicate the outcomes of the meeting via a brief consensus statement. The
      two specific aims of this statement are to encourage researchers in sport and
      exercise science to 1. Where possible, adopt research methods that more
      effectively elucidate the role of the brain in mediating the effects of
      treatments and interventions. 2. Where possible, adopt methods that factor for
      and/or quantify placebo effects that could explain a percentage of inter
      individual variability in response to treatments and intervention.

PMID- 30114974
TI  - The association between smoking and cardiometabolic risk among male adults with
      disabilities in Taiwan.
AB  - BACKGROUND: Individuals with disabilities have health needs similar to the
      general population. Smoking and metabolic syndrome have emerged as major
      cardiovascular risks that contribute to systemic inflammation and mortality.
      However, few studies have focused on the association between smoking and
      cardiometabolic risks in adult men with disabilities. AIMS: This study explored
      the prevalence of smoking and its association with cardiometabolic risk and
      associated factors among male adults with disabilities. METHODS: This study was
      part of a nurse-led health-promotion program designed to examine the health needs
      in health programs for adults with disabilities. A community-based, cross
      sectional study was conducted between July 2013-December 2014, in Chiayi County,
      Taiwan. RESULTS: Of the total of 964 male participants enrolled in this study,
      874 (90.7%) participants had complete data sets. The prevalence of cigarette
      smoking and metabolic syndrome were 42%, and 33.3%, respectively. More than half
      (62.7%) had high blood pressure and 43.5% had central obesity. Compared with non
      smokers, smokers tended to engage in less frequent regular exercise ( p<0.001),
      eat fewer vegetables and fruit ( p<0.05), and drink less water ( p<0.05). After
      adjusting for potential confounding variables, multivariable logistic regression
      analysis showed that smoking was an independent factor for cardiometabolic risk.
      CONCLUSION: The present findings show a high prevalence of cigarette smoking,
      unhealthy lifestyle, and cardiometabolic risk among adult men with disabilities.
      Clinicians and primary healthcare providers should reduce the consequences
      thereof by initiating innovative health promotion programs.

PMID- 30114975
TI  - Characteristics of sports participation and psychosocial health in children:
      Results of a cross-sectional study.
AB  - Several studies suggest that sports participation is beneficial for psychosocial
      health. There is, however, only a limited number of studies about the
      relationship of specific characteristics of sports participation with
      psychosocial health. The present study investigated associations between
      characteristics of sports participation and three aspects of psychosocial health,
      i.e. internalising problems, externalising problems and prosocial behaviour. The
      examined characteristics of sports participation pertained to individual versus
      team sports, indoor versus outdoor sports, involvement in competition or not, and
      contact sports versus non-contact sports. Cross-sectional data were collected
      from 1768 Dutch children aged 10-12 years who were member of a sports club. These
      children completed the Movement and Sports Monitor Questionnaire Youth aged 8-12
      years (MSMQ) and the Strength and Difficulties Questionnaire (SDQ). Linear
      multilevel analyses and logistic generalised estimating equation were conducted.
      Children participating in team sports, outdoor sports, or competition showed
      fewer internalising problems than children engaged in individual sports, indoor
      sports, or only training. The associations with internalising problems were
      stronger for boys than for girls. Children participating in non-contact sports
      showed fewer externalising problems than children performing non-contact sports
      as well as contact sports. Children practising indoor sports or non-contact
      sports showed better prosocial behaviour than children doing outdoor or contact
      sports. In conclusion, the form of sports participation seemed to matter highly
      with respect to internalising problems, especially for boys, and, to a lesser
      extent, with respect to externalising problems and prosocial behaviour. This
      offers starting points for developing tailor-made sports programmes for children.

PMID- 30114976
TI  - Bystander Intervention to Abusive Behavior on Social Networking Websites.
AB  - The current study assessed which bystander intervention behaviors individuals
      reported they would engage in when exposed to abuse in their online network and
      the correlates of these behaviors. Data were drawn from college students'
      responses ( N = 600) to three vignettes, ranging in severity, where the
      respondent's male friend commented about his ex-girlfriend on a social network.
      Although it was hypothesized respondents would intervene on the website when
      exposed to abuse, results suggested this was not the case. Respondents were more
      likely to offer support to the victim, report the behavior, and recommend
      programming for the most severe scenario. Implications are discussed.

PMID- 30114977
TI  - Equilibrium Distributions of Populations of Biological Species on Networks of
      Social Sites.
AB  - We investigate the problem of how a population of biological species would
      distribute over a given network of social sites so that their social contacts
      through the connected sites can be maximized (or minimized). This problem has
      applications in modelling the behaviours of social (or solitary) species such as
      the development of social groups in human society and the spread of solitary
      animals in distant habitats. We show that this problem can be formulated as an
      evolutionary game, with the equilibrium state of the game corresponding to a
      strategy for choosing the residing sites, each with a certain probability, or
      equivalently, to a distribution of the population on these sites. The game has a
      symmetric payoff matrix, and can therefore be analyzed via the solution of a
      corresponding quadratic programme: An equilibrium strategy of the game is a KKT
      point of the quadratic programme, which may be a local maximizer, local
      minimizer, or saddle point, but it is evolutionarily stable if and only if it is
      a strict local maximizer. In general, with a goal to maximize the social
      contacts, the species tend to spread on network sites where there are dense
      connections such as a complete subnetwork or in other words, a network clique. We
      show that at equilibrium, the population may or may not distribute on a network
      clique, but the stability of the equilibrium state does depend on the structure
      of the selected subnetwork. In particular, we show that the distribution of the
      population on a maximal network clique is evolutionarily stable unless the clique
      is 'attached' to another clique of the same or larger size, when the population
      may be able to switch or expand to the neighbouring clique to increase or at
      least maintain its total amount of contacts. However, the distribution of the
      population on a non-clique subnetwork is always evolutionarily unstable or weakly
      evolutionarily stable at the very best, for the population can always move away
      from its current distribution without decreasing its total amount of contacts. We
      conclude that the strategies to spread on maximal network cliques are not only
      equilibrium strategies but also evolutionarily more stable than those on non
      clique subnetworks, thus theoretically reaffirming the evolutionary advantages of
      joining social cliques in social networks for social species.

PMID- 30114978
TI  - Households' knowledge, attitudes, and practices toward solid waste management in
      suburbs of Phnom Penh, Cambodia.
AB  - This study developed logistic regression models to analyse the relationship
      between 12 observed variables on knowledge, attitudes, and practices toward solid
      waste management in the suburbs of Phnom Penh city. We interviewed 800
      households, including 200 collection service users and 600 non-service users. The
      determinants of how individuals are aware of, think of, and behave were assessed
      in the models based on the values of estimated coefficient and probability of t
      statistics. As a result, education level and knowledge of health effects have
      positive influences on knowledge of waste problems. Income is a decisive economic
      factor of knowledge and attitudes. The residents seem dissatisfied with the
      status of waste management and collection service if they are aware of the
      problems. The administration, therefore, needs improvements to satisfy the
      knowledgeable citizens. Service provision to the non-service users is imperative
      to halt the practice of illegal dumping. However, the infrequent collection still
      leads to the improper practice of the service users. We suggest that the service
      is provided widely, efficiently, and regularly.

PMID- 30114979
TI  - Investigation of construction wastes generated in the Malaysian residential
      sector.
AB  - The construction sector is among the fastest growing sectors in Malaysia; it
      consumes a vast amount of natural resources and produces a massive volume of
      construction and demolition waste. The waste is collected in a decentralised
      manner by sub-contracted companies. It is challenging to obtain reliable
      information on the amount of construction waste generated, because it is hard to
      determine its exact quantity and composition. Therefore, this study proposes a
      quantitative construction waste estimation model for residential buildings
      according to available data collected from the Construction Industry Development
      Board, Malaysia. In the development of this model, a theoretical investigation of
      the construction procedure and the construction waste generation process was
      conducted. The waste generated rate was determined as 25.79 kg m-2 for new
      residential constructions, which translates into about 553,406 t of anticipated
      waste annually.

PMID- 30114980
TI  - The acceptance and commitment therapy model in occupational rehabilitation of
      musculoskeletal and common mental disorders: a qualitative focus group study.
AB  - AIMS: The aim of this study was to examine whether and how intended processes of
      behavioural change were reflected in participants' experiences after an inpatient
      occupational rehabilitation programme. The programme was transdiagnostic, lasted
      31/2 weeks and was based on the acceptance and commitment therapy model. METHODS:
      Twenty-two participants (17 women and 5 men) took part in five qualitative focus
      group interviews after the programme. Analysis was data-driven, categorising
      participants' experiences using an initial explorative phenomenological approach.
      The emerging data-driven categories were re-contextualised within the theoretical
      framework of the therapy model. RESULTS: The participants referred to experiences
      within all three intended domains of the model (openness, awareness, and
      engagement). Our results indicate that the transdiagnostic approach may have
      facilitated openness, while the attainment of flexible self-awareness was less
      evident. Participants expressed engagement and behavioural changes linked to
      personal values, but did not mention actions leading to imminent return to work.
      CONCLUSIONS: The results imply that for implementation in occupational
      rehabilitation, further development of this model is needed specifically
      regarding processes related to self-awareness and committed action towards work.
      These findings are relevant for the interpretation of results from randomised
      clinical trials on acceptance and commitment therapy in occupational
      rehabilitation. Implications for rehabilitation Acceptance and commitment therapy
      seems to be a feasible component in an occupational rehabilitation programme for
      persons with different diagnoses. A transdiagnostic approach mixing
      musculoskeletal pain disorders and common mental disorders in the same
      rehabilitation programme seems to facilitate the process of openness and
      acceptance. There is a need to further develop and operationalise some of the
      processes in Acceptance and commitment therapy to accommodate the approach to the
      occupational rehabilitation context.

PMID- 30114982
TI  - Notice of Retraction

PMID- 30114981
TI  - Estrogen Receptor-alpha and Progesterone Receptor Expression in Mammary
      Proliferative Lesions of Female Pet Rabbits.
AB  - In breast cancer of women, the estrogen receptor-alpha (ERalpha) and progesterone
      receptor (PR) status has prognostic and therapeutic significance. The aim of this
      study was (1) to characterize by immunohistochemistry the expression of ERalpha
      and PR in nonneoplastic and neoplastic mammary gland tissue of pet rabbits and
      (2) to correlate the ERalpha/PR status and histological features. All 124 rabbits
      included in this study had a mammary tumor; in addition, 2 rabbits had lobular
      hyperplasia and 25 had multiple cysts. Of the 124 neoplasms, 119 (96%) were
      carcinoma, 2 (2%) were carcinoma in situ, and 3 (2%) were adenoma. ERalpha or PR
      or both were detected in 2 of 2 carcinomas in situ, 3 of 3 adenomas, 19 of 25
      cysts, and 2 of 2 lesions of lobular hyperplasia. Most carcinomas (75/119, 63%)
      were negative for both ERalpha and PR; 22 of 119 carcinomas (18%) were double
      immunopositive. The ERalpha and PR expression was not influenced by histotype or
      histological tumor grade. In carcinomas, there was a statistically significant
      correlation between increased mitotic count and reduced expression of ERalpha and
      PR, and the mitotic count was higher in double-immunonegative carcinomas
      (75/119). The findings suggest that in rabbit mammary carcinomas, proliferative
      activity is mainly influenced by factors other than estrogen and progesterone and
      provides the basis for future investigations into the prognostic significance of
      the ERalpha and PR status of mammary tumors.

PMID- 30114983
TI  - Non-pharmacologic treatments for symptoms of diabetic peripheral neuropathy: a
      systematic review.
AB  - OBJECTIVE: To systematically assess benefits and harm of non-pharmacologic
      interventions for diabetic peripheral neuropathy (DPN) symptoms. METHODS:
      MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were
      searched from 1966 to May 24, 2016 for randomized controlled trials. Two
      reviewers evaluated studies for eligibility, serially abstracted data, evaluated
      risk of bias, and graded strength of evidence (SOE) for critical outcomes (pain
      and quality-of-life). RESULTS: Twenty-three trials were included. For pain, alpha
      lipoic acid was more effective than placebo (moderate SOE) and frequency
      modulated electromagnetic stimulation was more effective than sham (low SOE) in
      the short-term but not the long-term. Electrical stimulation (including
      transcutaneous) was not effective for pain (low SOE). Spinal cord stimulation was
      more effective than usual care for pain (low SOE), but had serious complications,
      and studies had no sham arm. Evidence for cognitive behavioral therapy and
      acupuncture was insufficient; no exercise or physical therapy trials met
      inclusion criteria. No interventions reported sufficient evidence on quality-of
      life. Most studies were short-term with unclear risk of bias. CONCLUSIONS: Alpha
      lipoic acid and spinal cord stimulation were effective for pain; studies were
      short-term with quality deficits. Spinal cord stimulation had serious adverse
      events. Further research should address long-term outcomes and other non
      pharmacologic treatments.

PMID- 30114985
TI  - Adherence to health management guidelines for children with Down's syndrome at
      the Bustamante Hospital for Children, Jamaica.
AB  - Health surveillance of children with Down's syndrome may be inadequate. We aimed
      to assess adherence to health management guidelines at the main paediatric
      hospital in Jamaica. Ours was a retrospective descriptive study over a five-year
      period. Data on demographics, co-morbidities, investigations, referrals and
      interventions were recorded. Of 41 children included in the study, 85% were
      diagnosed in the neonatal period. Congenital heart disease in 29 (76%) and
      ophthalmological disorders in 13/24 (54%) were the most common co-morbidities.
      Evaluations in accordance with the American Academy of Pediatrics guidelines were
      carried out in only 46% of the children for echocardiography, 48% for
      ophthalmology, 30% for hearing evaluation and 10% for neonatal thyroid screening.
      Thus, the recommended guidelines were not carried out in a timely manner in the
      majority of the children. Education of healthcare providers and caregivers along
      with the provision of adequate resources may help to resolve this inadequacy.

PMID- 30114984
TI  - Featured Article: Deterioration of visual function mediated by senescence
      associated endoplasmic reticulum stress in inflammatory tie2-TNF mice.
AB  - Stress-associated premature senescence plays a major role in retinal diseases. In
      this study, we investigated the relationship between endothelial dysfunction,
      endoplasmic reticulum (ER) stress, and cellular senescence in the development of
      retinal dysfunction. We tested the hypothesis that constant endothelial
      activation by transmembrane tumor necrosis factor-alpha (tmTNF-alpha) exacerbates
      age-induced visual deficits via senescence-mediated ER stress in this model. To
      address this, we employed a mouse model of chronic vascular activation using
      endothelial-specific TNF-alpha-expressing (tie2-TNF) mice at 5 and 10 months of
      age. Visual deficits were exhibited by tie2-TNF mice at both 5 months and 10
      months of age, with the older mice showing statistically significant loss of
      visual acuity compared with tie2-TNF mice at age 5 months. The neural defects, as
      measured by electroretinogram (ERG), also followed a similar trend in an age
      dependent fashion, with 10-month-old tie2-TNF mice showing the greatest decrease
      in "b" wave amplitude at 25 cd.s.m2 compared with age-matched wildtype (WT) mice
      and five-month-old tie2-TNF mice. While gene and protein expression from the
      whole retinal extracts demonstrated increased inflammatory (Icam1, Ccl2), stress
      associated premature senescence (p16, p21, p53), and ER stress (Grp78, p
      Ire1alpha, Chop) markers in five-month-old tie2-TNF mice compared with five-month
      old WT mice, a further increase was seen in 10-month-old tie2-TNF mice. Our data
      demonstrate that tie2-TNF mice exhibit age-associated increases in visual
      deficits, and these data suggest that inflammatory endothelial activation is at
      least partly at play. Given the correlation of increased premature senescence and
      ER stress in an age-dependent fashion, with the loss of visual functions and
      increased endothelial activation, our data suggest a possible self-enhanced loop
      of unfolded protein response pathways and senescence in propagating neurovascular
      defects in this model. Impact statement Vision loss in most retinal diseases
      affects the quality of life of working age adults. Using a novel animal model
      that displays constant endothelial activation by tmTNF-alpha, our results
      demonstrate exacerbated age-induced visual deficits via premature senescence
      mediated ER stress. We have compared mice of 5 and 10 months of age, with highly
      relevant human equivalencies of approximately 35- and 50-year-old patients,
      representing mature adult and middle-aged subjects, respectively. Our studies
      suggest a possible role for a self-enhanced loop of ER stress pathways and
      senescence in the propagation of retinal neurovascular defects, under conditions
      of constant endothelial activation induced by tmTNF-alpha signaling.

PMID- 30114986
TI  - Tuberculosis of the thyroid in Togo: a clinicopathologic study of 11 presumed
      cases.
AB  - Tuberculosis (TB) remains a real public health concern in Africa; thyroid
      localisation of the disease is a very rare form of extrapulmonary TB. We
      conducted a descriptive and cross-sectional study on all histologically proved
      cases of thyroid TB diagnosed in Togo over the last 20 years. Eleven cases of TB
      of the thyroid were identified, of which nine were in women, with an average age
      of 29.4 +/- 0.2 years. The clinical signs were the presence of a nodule in seven,
      an abscess in three and a swelling with cutaneous fistulisation in one. Thyroid
      involvement alone was found in four, associated with pleuropulmonary TB in six
      and mammary TB in one. Human immunodeficiency virus (HIV) co-infection was
      present in six. All histopathology results showed inflammatory granulomata with
      caseous necrosis. The clinical features are often misleading and pose a real
      diagnostic problem, especially with differentials of simple abscess and cancer.

PMID- 30114987
TI  - Comparison of cyanoacrylate embolization and radiofrequency ablation for the
      treatment of varicose veins.
AB  - Objective To review clinical outcomes of varicose vein patients treated with
      cyanoacrylate embolization and radiofrequency ablation at our institution.
      Methods A retrospective review of patients who underwent cyanoacrylate
      embolization and radiofrequency ablation during a three-year period. Patient
      records were reviewed to assess demographics, location and severity of disease,
      treatment details and outcome at short- and mid-term follow-ups. Outcome
      parameters included treatment success and complications. Results Between January
      2014 and December 2016, 335 patients with 476 veins were treated with either
      cyanoacrylate embolization (n = 148) or radiofrequency ablation (n = 328) at the
      Vancouver General Hospital Vascular Surgery Vein Clinic. The average age of
      patients were 57 +/- 1 years with the majority being female (78%) and an average
      BMI of 24.8 +/- 0.5. CEAP classes were 2 (49%), 3 (26%), 4a (22%) and >4b (3%).
      Of the veins treated with cyanoacrylate embolization, the vein types were as
      follows: 76% were great saphenous vein, 16% were small saphenous vein, 5% were
      anterior accessory great saphenous vein and 1.4% were perforator veins. The vein
      types for radiofrequency ablation were 88%, 9%, 3% and 0%, respectively. The
      average amount of cyanoacrylate embolization delivered for great saphenous vein
      treatment was 1.8 +/- 0.1 ml with a treatment length of 43 +/- 1 cm. Subgroup
      comparison was done for great saphenous vein segments. Treatment success was 100%
      in cyanoacrylate embolization and 99% in radiofrequency ablation. Superficial
      phlebitis was the most common complication noted at mid-term follow-up in 5% of
      cyanoacrylate embolization and 16% of radiofrequency ablation treatments (P <
      0.05). One patient in each group had asymptomatic proximal thrombus extension
      treated with anticoagulation for 2-3 weeks. Three superficial infections from
      glue clumps were noted in the cyanoacrylate embolization group requiring excision
      and drainage. Five patients in the radiofrequency ablation group had persistent
      numbness and one wound complications at the access site. Conclusion Cyanoacrylate
      embolization offers equivalent success rates with lower mid-term complication
      rates as radiofrequency ablation.

PMID- 30114988
TI  - Brain Processing (Auditory Event-Related Potential) of Stressed Versus Unstressed
      Words in Thai Speech.
AB  - This study investigated the effect of the stressed word in Thai language on
      auditory event-related potential (aERP) in unattended conditions. We presented 30
      healthy participants with monosyllabic Thai words consisting of either stressed
      or unstressed words. We instructed them not to attend to the sound stimuli, but
      rather to watch and memorize the contents of a silent natural documentary without
      subtitles. The two listening conditions consisted of 20% deviant stimuli (70
      stressed and 70 unstressed words, respectively) and 80% standard stimuli (other
      280 unstressed words) presented pseudorandomly and binaurally via a pair of
      earphones. Participants' aERPs from the two conditions were evaluated by the
      mismatch negativity (MMN) component of aERP. The mismatch negativity amplitudes
      in the stressed word condition were significantly higher than those in the
      unstressed word condition, especially in frontal and left fronto-central brain
      areas. Therefore, these data show the role of the frontal and left fronto-central
      brain regions in auditory preattentive processing of stressed word perception
      among native Thai speakers. This is the first study demonstration that stressed
      meaningful monosyllable words in tonal language facilitate word perception in
      this preattentive stage. This result has implications for developing clinical
      tests evaluating preattentive speech perception.

PMID- 30114989
TI  - Social transformation, collective health and community-based arts: 'Buen Vivir'
      and Ecuador's social circus programme.
AB  - Worldwide, interest is increasing in community-based arts to promote social
      transformation. This study analyzes one such case. Ecuador's government, elected
      in 2006 after decades of neoliberalism, introduced Buen Vivir ('good living'
      derived from the Kichwan sumak kawsay), to guide development. Plans included
      launching a countrywide programme using circus arts as a sociocultural
      intervention for street-involved youth and other marginalised groups. To examine
      the complex ways by which such interventions intercede in 'ways of being' at the
      individual and collective level, we integrated qualitative and quantitative
      methods to document relationships between programme policies over a 5-year period
      and transformations in personal growth, social inclusion, social engagement and
      health-related lifestyles of social circus participants. We also conducted
      comparisons across programmes and with youth in other community arts. While
      programmes emphasising social, collective and inclusive pedagogy generated
      significantly better wellbeing outcomes, economic pressures led to prioritising
      productive skill-building and performing. Critiques of the government's
      operationalisation of Buen Vivir, including its ambitious technical goals and
      pragmatic economic compromising, were mirrored in social circus programmes.
      However, the programme seeded a grassroots social circus movement. Our study
      suggests that creative programmes introduced to promote social transformation can
      indeed contribute significantly to nurturing a culture of collective wellbeing.

PMID- 30114991
TI  - Florid reactive periostitis of the metacarpal bone: a case of resolution without
      resection.

PMID- 30114990
TI  - Asymptomatic reference values for the Disability of Arm, Shoulder and Hand and
      Patient-Rated Wrist/Hand Evaluation - electronic data collection and its clinical
      implications.
AB  - The purpose of this study was to establish normal asymptomatic population values
      for the Disability of Arm, Shoulder and Hand and Patient-Rated Wrist/Hand
      Evaluation in healthy, asymptomatic individuals of different age, gender,
      ethnicity, handedness and nationality, using electronic data collection. Two
      hundred and ninety-two Australian and 293 Canadian citizens with no active wrist
      pain, injury or pathology in their dominant hand, were evaluated. Participants
      completed an electronically administered questionnaire and were assessed
      clinically. There was no statistically significant association between both wrist
      scores and nationality. There was a statistically significant association between
      both wrist scores and age, demonstrating that as age increased, normal wrist
      function declined. This study has established an electronic, asymptomatic control
      group for future studies using these scores. When using the Disability of Arm,
      Shoulder and Hand and Patient-Rated Wrist/Hand Evaluation, the control group can
      be sourced from a pre-established control group within a database, without
      necessarily being sourced from the same country of origin. Level of evidence: II.

PMID- 30114992
TI  - Nodular granulomatous Pneumocystis jiroveci pneumonia consequent to delayed
      immune reconstitution inflammatory syndrome.
AB  - Although Pneumocystis jiroveci pneumonia (PCP) is a frequent manifestation of
      acquired immune deficiency syndrome (AIDS), the granulomatous form is uncommon.
      Here, we present an unusual case of granulomatous PCP consequent to immune
      reconstitution inflammatory syndrome (IRIS) after highly active antiretroviral
      therapy. A 36-year-old woman with human immunodeficiency virus (HIV) presented
      with cough and dyspnea that were attributed to typical PCP associated with AIDS.
      She was successfully treated with antibiotic, steroid, and antiretroviral
      therapies. After six months, however, she presented with consolidating lung
      lesions caused by bronchial obstruction from PCP granulomatous disease. Although
      antibiotics were ineffective, the effectiveness of steroid therapy suggested a
      diagnosis of granulomatous IRIS caused by persistent PCP antigens. Physicians
      should strongly suspect PCP in HIV-positive patients with nodular lung lesions
      and must remain aware that these lesions, if immune in origin, might not respond
      to antimicrobial therapy.

PMID- 30114993
TI  - Rectal Trichomonas vaginalis infection in South African men who have sex with
      men.
AB  - This study from South Africa highlights the importance of rectal Trichomonas
      vaginalis infection as a sexually transmitted infection among men who have sex
      with men (MSM). We report seven MSM presenting with rectal T. vaginalis
      infection. Two men presented with symptoms of proctitis; 5/7 had urethral
      coinfection with T. vaginalis. Rectal T. vaginalis infection should be considered
      in MSM in areas where genital infection is endemic.

PMID- 30114994
TI  - Congenital syphilis presenting with liver lesions.
AB  - Congenital syphilis is a prevalent infection in much of the world but rare in
      contexts where antenatal screening and treatment are available. In the UK in
      2016, three cases of congenital syphilis were reported in babies born to women
      who were seronegative at the time of booking and hence a high degree of clinical
      vigilance is required in the unwell infant. We present the case of a seven-week
      old baby girl with congenital syphilis with the unusual finding of discrete liver
      lesions. This baby was successfully treated with intravenous ceftriaxone.

PMID- 30114995
TI  - Sexual behaviours and sexually transmitted infection outcomes in a cohort of HIV
      negative men who have sex with men attending sexual health clinics in England.
AB  - Men who have sex with men (MSM) attending sexual health (SH) clinics are at high
      risk for HIV acquisition and are disproportionately affected by sexually
      transmitted infections (STIs). We collected standardised behavioural data from
      MSM attending clinics to characterise sexual behaviours and identify predictors
      for HIV and STIs. In 2012-2013, HIV-negative MSM attending five SH clinics in
      England reported sexual behaviours in the previous three months via a self
      administered questionnaire. Behaviours were linked to the individual's clinical
      records using national surveillance. The prevalence and incidence of bacterial
      STIs (gonorrhoea, Chlamydia, lymphogranuloma venereum and syphilis) and incidence
      of HIV were calculated. Adjusted odds ratios and hazard ratios with 95%
      confidence interval (CI) were reported for significant predictors. Of 1278 HIV
      negative MSM, 54% were of white ethnicity and UK-born and 43% were 25-34 years
      old. Almost all men reported at least one partner in the last three months. Half
      reported condomless anal sex and 36% condomless receptive anal intercourse
      (CRAI). Incidence of bacterial STIs was 46/100 (95%CI 39-54) person years (py)
      and of HIV was 3.1/100 (95%CI 1.7-5.6) py. A STI at baseline and CRAI with
      increasing numbers of partners were associated with both incident infections. In
      this cohort of MSM high-risk behaviours and STIs were prevalent. Engagement in
      CRAI increased the likelihood of subsequent infection, while men diagnosed with a
      bacterial STI were at increased risk of a future STI. Clinical and behavioural
      risk assessments to determine an individual's risk of infection could allow a
      more nuanced prevention approach that has greater success in reducing
      transmission.

PMID- 30114996
TI  - Urinary liver-type fatty acid-binding protein levels as a potential risk factor
      for renal dysfunction in male HIV-infected Japanese patients receiving
      antiretroviral therapy: a pilot study.
AB  - Renal dysfunction is recognized with increasing frequency among the non
      infectious co-morbidities associated with human immunodeficiency virus (HIV)
      infection. Recently, urinary liver-type fatty acid-binding protein (L-FABP) was
      suggested to be a predictor of the progression of renal dysfunction in patients
      without HIV. However, little is known regarding the utility of urinary L-FABP as
      a predictor of renal dysfunction in patients with HIV. A retrospective,
      observational, single-centre study was conducted between July 2014 and December
      2016. The primary outcome was renal dysfunction defined as decrease in estimated
      glomerular filtration rate to less than 60 ml/min/1.73 m2. To estimate the effect
      of urinary L-FABP, proteinuria category, and urinary beta2 microglobulin
      (beta2MG) on the time to the first event, a log-rank test was performed.
      Accuracy, determined by area under the curve and calculated from receiver
      operating characteristic curves, was also assessed. Thirty Japanese outpatients
      with HIV receiving antiretroviral therapy (ART) were enrolled. The primary
      outcome occurred in five patients during the follow-up period. Urinary L-FABP
      level and proteinuria category were significantly associated with renal
      dysfunction (p = 0.045 and p = 0.037, respectively). In contrast, urinary beta2MG
      level was not significantly associated with renal dysfunction (p = 0.141).
      Urinary L-FABP was the most accurate predictor of renal dysfunction among the
      three urinary parameters. In conclusion, urinary L-FABP levels in HIV patients
      receiving ART were more accurate for predicting renal dysfunction than
      proteinuria and urinary beta2MG. In addition, urinary L-FABP helped to
      discriminate those patients with a higher risk for renal dysfunction.

PMID- 30114997
TI  - Lessons from a decade of voluntary medical male circumcision implementation and
      their application to HIV pre-exposure prophylaxis scale up.
AB  - Oral pre-exposure prophylaxis (PrEP) has the ability to curb HIV incidence
      worldwide and bring us closer to ending the HIV epidemic. Scale up of PrEP
      service delivery has many similar challenges to those faced by voluntary medical
      male circumcision (VMMC) services roll-out. This article outlines ten important
      lessons learned during the scale up of VMMC services in sub-Saharan Africa and
      their application to current oral PrEP implementation efforts to promote faster
      expansion for public health impact.

PMID- 30114998
TI  - Reactive hemophagocytic syndrome in the setting of acute human immunodeficiency
      virus 1 infection: case report and review of the literature.
AB  - We report a case of reactive hemophagocytic syndrome (RHS) in the setting of
      acute human immunodeficiency virus type 1 infection (AHI). In addition, we review
      11 previously reported cases of RHS precipitated by AHI and discuss strategies in
      the diagnosis and management of these overlapping clinical entities.

PMID- 30114999
TI  - Treatment of disseminated histoplasmosis in advanced HIV using itraconazole with
      increased bioavailability.
AB  - Disseminated histoplasmosis (DH), an endemic mycosis caused by the dimorphic
      fungus Histoplasma capsulatum, is a life-threatening infection in
      immunocompromised hosts. A patient with newly-diagnosed human immunodeficiency
      virus (HIV) infection presented with a violaceous, raised, indurated, pruritic
      rash over the face, arms and trunk on a background of significant weight loss,
      fevers with sweats, diarrhoea and worsening shortness of breath. His CD4+ T cell
      count was 14 cells/ul (12%). Histoplasmosis was diagnosed from histology, fungal
      stain and culture of skin biopsy. In addition to DH, he was found to have
      Pneumocystis jiroveci pneumonia and multi-resistant Salmonella choleraesuis
      bacteraemia. He improved with treatment with antibiotics and was commenced on
      conventional itraconazole, orally. Antiretroviral therapy was commenced soon
      after. He was unable to achieve therapeutic levels with the conventional
      formulation due to gastrointestinal side effects and had ongoing fevers. A newer
      formulation of oral itraconazole with improved bioavailability was commenced. He
      achieved therapeutic drug levels and had no further intolerance. His fevers
      settled and the rash improved. He has now completed one year of treatment and is
      well. To our knowledge this is the first case of moderate DH in an advanced HIV
      patient treated successfully with oral itraconazole with improved
      bioavailability.

PMID- 30115000
TI  - Repeat HIV testing among HIV-uninfected men who have sex with men attending Silom
      Community Clinic, Bangkok, 2011 - 2014.
AB  - Since 2010, the Thailand Ministry of Public Health has recommended that men who
      have sex with men (MSM) have an HIV test at least two times a year. We calculated
      the proportion of, and factors associated with, testing adherence among the HIV
      uninfected MSM clients attending Silom Community Clinic @TropMed. We defined
      testing adherence as repeating at least one HIV test within six months of an
      initial HIV-negative test, and used log-binomial regression to test for
      associated factors. We included 1927 clients during 2011-2014; 362 (19%) were
      adherent with an increased trend ( p < 0.01), from 16% to 24%. Clients aged 18-24
      years and those having a history of HIV testing were more likely to adhere (aRR:
      1.3, 95% CI: 1.1-1.6; and aRR: 1.3, 95% CI: 1.0-1.5, respectively). One-fifth
      adhered to the recommendation; older clients or naive testees were less likely to
      adhere. We need to impress on clients the importance of repeat HIV testing.

PMID- 30115002
TI  - The effect of playing status, maturity status, and playing position on the
      development of match skills in elite youth football players aged 11-18 years: A
      mixed-longitudinal study.
AB  - This mixed-longitudinal study examined the development of match skills in elite
      male youth footballers (aged 11-18 years), while considering the effect of
      playing status, maturity status, and playing position. Across two seasons, 126
      elite male youth footballers were assessed in 1-10 competitive matches (401
      player-matches). For each match, the on-the-ball actions of each player were
      recorded using a notation system. The match skills observed were frequencies of
      successful passes, on-target shots, dribbles, crosses, clearances, and
      tackles/blocks/interceptions. Multilevel Poisson analysis was used to model the
      development of players, with regard to each match skill. Modelling revealed
      significant (p < .05) age-related changes in the frequency of several match
      skills. That is, dribbles increased, on-target shots, crosses and
      tackles/blocks/interceptions decreased, whereas changes in successful passes were
      position-specific. Players retained by an academy performed more dribbles
      compared to released players (p < .05) (e.g. retained vs. released 18-year-old
      centre forward = 4.1 vs. 2.0 dribbles per hour), and retained defenders performed
      more tackles/blocks/interceptions than released defenders (p < .05) (e.g.
      retained vs. released 18-year-old, on-time maturing centre back = 12.5 vs. 10.2
      tackles/blocks/interceptions per hour). Moreover, compared to on-time maturing
      players, early maturing players performed more tackles/blocks/interceptions (p <
      .05) (e.g. on-time vs. early maturing retained 18-year-old centre back = 12.5 vs.
      15.2 tackles/blocks/interceptions per hour). Playing position affected all match
      skills (p < .05). The developmental profiles of match skills presented here may
      support experts in identifying and developing talented footballers across a wide
      age range, while considering the influence of maturity status and playing
      position.

PMID- 30115001
TI  - Systematic assessment of decision-analytic models evaluating diagnostic tests for
      acute myocardial infarction based on cardiac troponin assays.
AB  - INTRODUCTION: Despite the emphasis on the clinical importance of cardiac troponin
      assays (cTn), there are insufficient cost-effectiveness comparisons of various
      troponin test protocols for the diagnosis of myocardial infarction (MI).
      Therefore, the purpose of the review was to identify and systematically assess
      published economic evaluations using decision-analytic models for diagnostic
      testing strategies based on cTn and to make recommendations for the development
      of future models. Areas covered: MEDLINE, Science Direct, Cochrane Database, CRD
      Database, and gray literature were screened for full economic evaluation studies
      with relevant clinical outcomes over a defined time horizon addressing a
      population with suspected MI and comparison of different diagnostic test
      strategies. Standardized forms for data extraction and evidence tables were used
      for the summary of study design, methodological framework and data sources.
      Studies were assessed for quality using the CHEERS and the BMJ checklists. Expert
      commentary: Although there are 11 identified studies and several well-designed
      models, there remains a need for decision-analytic models including differential
      diagnosis for acute MI, different health facility configurations, clinician
      preferences, and behavioral components, and in the top of the subgroup analyses
      additional important personalized medicine aspects.

PMID- 30115003
TI  - Spoilers Affect the Enjoyment of Television Episodes but Not Short Stories.
AB  - While spoilers are culturally regarded as something that detracts enjoyment from
      a narrative, research has presented a complicated picture. When Leavitt and
      Christenfeld presented participants plot-crucial information to individuals
      before reading a short story, the story was subsequently enjoyed as much as, or
      more than, unspoiled stories. Other research shows that these findings may be
      driven by an interaction of individual differences, such as need for cognition,
      rather than a broad spoiling effect. In Experiment 1, we tested if reported
      enjoyment of a narrative decreased even when participants were alerted to the
      presence of a plot spoiler, to extend previous findings for short stories while
      adding a condition informing participants beforehand that their short stories was
      being spoiled. Experiment 2 extended this methodology to full-length episodes of
      television. Our results were different from previously reported positive effects
      of spoilers and show that spoilers, under certain circumstances, have a negative
      effect on enjoyment for television but not short stories.

PMID- 30115004
TI  - Unemployment Normalization: Its Effect on Mental Health During Various Stages of
      Unemployment.
AB  - The negative effects of job loss on mental health have been thoroughly described
      in the literature. However, different fluctuations in mental health during the
      unemployment period have been noticed. We argue that a coping process takes place
      in this kind of situation. Therefore, in this study, we investigated the effect
      of the unemployment normalization process on mental health during various stages
      of unemployment. Participants ( N = 803) completed the General Health
      Questionaire-12 and the Unemployment Normalization Questionnaire. Results showed
      that a negative perception of unemployment had the greatest impact on mental
      health during the different phases of unemployment. Nevertheless, during the
      first year, having a positive perception counteracted these negative effects, and
      after 1 year, the unemployment norm took over the role of buffering against the
      negative effects on mental health. These results indicate that unemployment is
      still perceived as negative, but depending on the stage of unemployment, various
      coping strategies are used to buffer the negative consequences of unemployment.

PMID- 30115005
TI  - Acceptance of Workplace Bullying Behaviors and Job Satisfaction: Moderated
      Mediation Analysis With Coping Self-Efficacy and Exposure to Bullying.
AB  - Previous research explored workplace climate as a factor of workplace bullying
      and coping with workplace bullying, but these concepts were not closely related
      to workplace bullying behaviors (WBBs). To examine whether the perceived exposure
      to bullying mediates the relationship between the climate of accepting WBBs and
      job satisfaction under the condition of different levels of WBBs coping self
      efficacy beliefs, we performed moderated mediation analysis. The Negative Acts
      Questionnaire - Revised was given to 329 employees from Serbia for assessing
      perceived exposure to bullying. Leaving the original scale items, the instruction
      of the original Negative Acts Questionnaire - Revised was modified for assessing
      (1) the climate of accepting WBBs and (2) WBBs coping self-efficacy beliefs.
      There was a significant negative relationship between exposure to bullying and
      job satisfaction. WBB acceptance climate was positively related to exposure to
      workplace bullying and negatively related to job satisfaction. WBB acceptance
      climate had an indirect relationship with job satisfaction through bullying
      exposure, and the relationship between WBB acceptance and exposure to bullying
      was weaker among those who believed that they were more efficient in coping with
      workplace bullying. Workplace bullying could be sustained by WBB acceptance
      climate which threatens the job-related outcomes. WBBs coping self-efficacy
      beliefs have some buffering effects.

PMID- 30115006
TI  - Five-Factor Model Best Describes Narcissistic Personality Inventory Across
      Different Item Response Formats.
AB  - The objective of this research was to validate the Narcissistic Personality
      Inventory across different response formats, given that several factor structures
      were proposed, ranging from two to seven factors. The original forced-choice
      format of the Narcissistic Personality Inventory was given to 410 participants
      and a modified, i.e., Likert format was given to 423 participants from the
      general population, along with personality and other narcissism measures. The
      results showed that the five-factor model proposed by Ackerman et al. had the
      best model fit in both response formats and that a distinction between adaptive
      (Leadership, Vanity, and Superiority) and some aspects of maladaptive
      (Manipulativeness and Exhibitionism) narcissism factors could be established.
      However, the redundancy of items in certain factors could be problematic and
      further improvements of the Narcissistic Personality Inventory should include
      more indicators of some proposed factors, especially of Vanity.

PMID- 30115007
TI  - Early postoperative recovery in operating room after desflurane anesthesia
      combined with Bispectral index (BIS) monitoring and warming in lengthy abdominal
      surgery: a randomized controlled study.
AB  - BACKGROUND: This study aimed to determine whether the use of desflurane (DES)
      anesthesia combined with bispectral index (BIS) monitoring and warming is
      effective in reducing anesthesia-controlled operating room time (ACT) in patients
      undergoing lengthy abdominal surgery. METHODS: Seventy patients, 40 years of age
      or older, undergoing abdominal surgery expected to last three to five hours were
      randomly assigned to the DES group (n = 35) or the control group (n = 35).
      Patients in the DES group were maintained with desflurane anesthesia and received
      BIS monitoring and warming. Patients in the control group were given non
      desflurane anesthesia for maintenance, and the usage of BIS monitoring and
      warming were not mandatory and determined by anesthesia care providers. Early
      postoperative recovery times were recorded. RESULTS: The times to extubation (8.8
      +/- 8.5 vs 14.7 +/- 13.7 min, P = 0.035), eye opening (8.4 +/- 8.6 vs 14.4 +/-
      13.4 min, P = 0.028), responds on command (8.2 +/- 8.5 vs 14.4 +/- 13.0 min, P =
      0.022), and the ACT (23.8 +/- 11.4 vs 32.7 +/- 15.4 min, P = 0.009) were
      significantly less in the DES group than that in the control group. The
      postanesthesia care unit (PACU) length of stay, incidence of prolonged
      extubation, and surgeon and anesthesiologist satisfaction were similar in two
      groups. Also, the result of multivariable linear regressions showed that patients
      who were younger, female, lower BMI and non-DES anesthesia regimen resulted in
      prolonged extubation. CONCLUSIONS: Desflurane anesthesia combined with BIS
      monitoring and warming is associated with early postoperative recovery in lengthy
      abdominal surgery. TRIAL REGISTRATION: ChiCTR-INR-17013333 . Date of
      registration: November 11, 2017.

PMID- 30115008
TI  - The importance of trust-based relations and a holistic approach in advance care
      planning with people with dementia in primary care: a qualitative study.
AB  - BACKGROUND: ACP enables individuals to define and discuss goals and preferences
      for future medical treatment and care with family and healthcare providers, and
      to record these goals and preferences if appropriate. Because general
      practitioners (GPs) often have long-lasting relationships with people with
      dementia, GPs seem most suited to initiate ACP. However, ACP with people with
      dementia in primary care is uncommon. Although several barriers and facilitators
      to ACP with people with dementia have already been identified in earlier
      research, evidence gaps still exist. We therefore aimed to further explore
      barriers and facilitators for ACP with community-dwelling people with dementia.
      METHODS: A qualitative design, involving all stakeholders in the care for
      community-dwelling people with dementia, was used. We conducted semi-structured
      interviews with community dwelling people with dementia and their family
      caregivers, semi structured interviews by telephone with GPs and a focus group
      meeting with practice nurses and case managers. Content analysis was used to
      define codes, categories and themes. RESULTS: Ten face to face interviews, 10
      interviews by telephone and one focus group interview were conducted. From this
      data, three themes were derived: development of a trust-based relationship,
      characteristics of an ACP conversation and the primary care setting. ACP is
      facilitated by a therapeutic relationship between the person with dementia/family
      caregiver and the GP built on trust, preferably in the context of home visits.
      Addressing not only medical but also non-medical issues soon after the dementia
      diagnosis is given is an important facilitator during conversation. Key barriers
      were: the wish of some participants to postpone ACP until problems arise, GPs'
      time restraints, concerns about the documentation of ACP outcomes and concerns
      about the availability of these outcomes to other healthcare providers.
      CONCLUSIONS: ACP is facilitated by an open relationship based on trust between
      the GP, the person with dementia and his/her family caregiver, in which both
      medical and non-medical issues are addressed. GPs' availability and time
      restraints are barriers to ACP. Transferring ACP tasks to case managers or
      practice nurses may contribute to overcoming these barriers.

PMID- 30115010
TI  - Visceral, general, abdominal adiposity and atherogenic index of plasma in
      relatively lean hemodialysis patients.
AB  - BACKGROUND: Obesity is a well-established risk factor for atherosclerosis.
      However, it is unknown which measure of adiposity best relates to atherosclerosis
      in relatively lean maintenance hemodialysis (MHD) patients. We aimed to explore
      and compare the associations between different adiposity indices reflecting
      general, abdominal, visceral adiposity and arteriosclerosis risk with atherogenic
      index of plasma(AIP) in relatively lean MHD patients. METHODS: We conducted a
      multicenter, cross-sectional study in Guizhou Province, Southwest China.
      General/abdominal adiposity indices like body mass index (BMI), waist
      circumference(WC), waist-height ratio(WHtR), conicity index (Ci) and visceral
      obesity indices including visceral adiposity index (VAI), lipid accumulation
      product (LAP) and the hypertriglyceridemic waist phenotype (HW phenotype) were
      recorded. Univariate and multivariate linear regression models were used.
      RESULTS: All adiposity indices correlated positively with AIP in univariate
      analysis both in men and women except for Ci. After adjustment for age and
      traditional atherosclerosis risk factors, BMI, WC, WHtR, VAI and LAP still had
      associations with AIP both in men (beta = 0.265, 0.153, 0.16, 0.788 and 0.74,
      respectively, all P < 0.001) and women (beta = 0.34,0.199, 0.21, 0.83 and 0.74,
      respectively, all P < 0.001). After further adjustment for BMI, associations
      between AIP and VAI, LAP remained significant, but associations between WC, WHtR
      and AIP disappeared. CONCLUSIONS: The HW phenotype, VAI, and LAP, validated and
      convenient markers of visceral obesity, were superior to classical anthropometric
      general/ abdominal adiposity indices for atherosclerosis risk assessment,
      especially in relatively lean MHD patients aged 40 years or older.

PMID- 30115009
TI  - Discovery and genome characterization of three new Jeilongviruses, a lineage of
      paramyxoviruses characterized by their unique membrane proteins.
AB  - BACKGROUND: In the past decade, many new paramyxoviruses that do not belong to
      any of the seven established genera in the family Paramyxoviridae have been
      discovered. Amongst them are J-virus (JPV), Beilong virus (BeiPV) and Tailam
      virus (TlmPV), three paramyxovirus species found in rodents. Based on their
      similarities, it has been suggested that these viruses should compose a new
      genus, tentatively called 'Jeilongvirus'. RESULTS: Here we present the complete
      genomes of three newly discovered paramyxoviruses, one found in a bank vole
      (Myodes glareolus) from Slovenia and two in a single, co-infected Rungwe brush
      furred rat (Lophuromys machangui) from Mozambique, that represent three new,
      separate species within the putative genus 'Jeilongvirus'. The genome
      organization of these viruses is similar to other paramyxoviruses, but like JPV,
      BeiPV and TlmPV, they possess an additional open reading frame, encoding a
      transmembrane protein, that is located between the F and G genes. As is the case
      for all Jeilongviruses, the G genes of the viruses described here are unusually
      large, and their encoded proteins are characterized by a remarkable amino acid
      composition pattern that is not seen in other paramyxoviruses, but resembles
      certain motifs found in Orthopneumovirus G proteins. CONCLUSIONS: The
      phylogenetic clustering of JPV, BeiPV and TlmPV with the viruses described here,
      as well as their shared features that set them apart from other paramyxoviruses,
      provide additional support for the recognition of the genus 'Jeilongvirus'.

PMID- 30115011
TI  - The effect of patient positions on perfusion index.
AB  - BACKGROUND: The optimal position for surgery is one in which the patient is
      provided the best possible surgical intervention and put at minimum risk.
      Different surgical positions may cause changes in tissue perfusion. This study
      investigates the relationship between surgical patient positions and perfusion
      index. METHODS: A sample of 61 healthy individuals with no peripheral circulatory
      disorders, chronic diseases, or anemia was included in this study. Participants
      held six different positions: supine, prone, 45-degree sitting-supine, 45-degree
      supine with legs lifted, Trendelenburg (45-degrees head down), and reverse
      Trendelenburg (45-degrees head up). Perfusion index values were then measured and
      recorded after individuals held their positions for five minutes. RESULTS:
      Participants' perfusion index values were affected by different body positions (p
      < 0.05). Perfusion index was lowest in the sitting position (4.5 +/- 2.5) and
      highest in individuals with Trendelenburg position (7.8 +/- 3.8). CONCLUSION:
      Different body positions can cause changes in tissue perfusion. This should be
      considered in patient follow-up along with the perfusion index.

PMID- 30115013
TI  - Adult minimal-change disease: observational data from a UK centre on patient
      characteristics, therapies, and outcomes.
AB  - BACKGROUND: Minimal change disease (MCD) is a common cause of the nephrotic
      syndrome in adults with limited evidence on its treatment and prognosis. We
      examined the presenting characteristics, treatments, and outcomes of adult
      patients with MCD in our centre. METHODS: This was an observational cohort study
      using retrospectively-collected data. All patients who had a renal biopsy
      reported as MCD between 1996 and 2012 were included, and data were collected at
      baseline and during follow-up. Statistical analysis included Cox-regression
      analysis to examine which factors were associated with risk of relapse. RESULTS:
      Seventy-eight patients were included, and had a median age of 36 years, and were
      60% male and 73% white. Median follow-up time was 72 months. 37% were in AKI at
      presentation, which was significantly associated with a lower serum albumin and
      older age. Although 10% were steroid-resistant, 98% achieved remission at a
      median time of 5 weeks. 61% relapsed, at a median time of 11 months, and patients
      had a median number of 2 relapses during follow-up. A higher eGFR was associated
      with an increased risk of relapse (hazard ratio 1.18 [1.03-1.36] per 10 mL/min
      increase in eGFR), and females were significantly more likely than males to have
      an early relapse. Nearly half of the cohort required an additional
      immunosuppressive agent on top of glucocorticoids, the most commonly used being
      calcineurin inhibitors. Five patients subsequently developed FSGS: these patients
      had a lower baseline creatinine, a higher serum albumin, a longer time to
      remission, and were more likely to be steroid-resistant. Follow-up renal function
      was generally preserved, but follow-up creatinine was higher in those who had
      presented with AKI, and in those who had been commenced on a RAS inhibitor after
      biopsy. Infection requiring admission, diabetes mellitus and venous
      thromboembolism developed in 14%, 12%, and 12% of patients respectively.
      CONCLUSIONS: Nearly all adults with MCD achieve remission, but relapses and
      disease- and therapy-related complications are common. In our cohort, eGFR and
      gender were associated with risk of relapse, and these previously undescribed
      associations could be explored further in future work.

PMID- 30115012
TI  - Structure and function of a lignostilbene-alpha,beta-dioxygenase orthologue from
      Pseudomonas brassicacearum.
AB  - BACKGROUND: Stilbene cleaving oxygenases (SCOs), also known as lignostilbene
      alpha,beta-dioxygenases (LSDs) mediate the oxidative cleavage of the olefinic
      double bonds of lignin-derived intermediate phenolic stilbenes, yielding small
      modified benzaldehyde compounds. SCOs represent one branch of the larger
      carotenoid cleavage oxygenases family. Here, we describe the structural and
      functional characterization of an SCO-like enzyme from the soil-born, bio-control
      agent Pseudomonas brassicacearum. METHODS: In vitro and in vivo assays relying on
      visual inspection, spectrophotometric quantification, as well as liquid
      chormatographic and mass spectrometric characterization were applied for
      functional evaluation of the enzyme. X-ray crystallographic analyses and in
      silico modeling were applied for structural investigations. RESULTS: In vitro
      assays demonstrated preferential cleavage of resveratrol, while in vivo analyses
      detected putative cleavage of the straight chain carotenoid, lycopene. A high
      resolution structure containing the seven-bladed beta-propeller fold and
      conserved 4-His-Fe unit at the catalytic site, was obtained. Comparative
      structural alignments, as well as in silico modelling and docking, highlight
      potential molecular factors contributing to both the primary in vitro activity
      against resveratrol, as well as the putative subsidiary activities against
      carotenoids in vivo, for future validation. CONCLUSIONS: The findings reported
      here provide validation of the SCO structure, and highlight enigmatic points with
      respect to the potential effect of the enzyme's molecular environment on
      substrate specificities for future investigation.

PMID- 30115015
TI  - The association between socioeconomic disparities and left ventricular
      hypertrophy in chronic kidney disease: results from the KoreaN Cohort Study for
      Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD).
AB  - BACKGROUND: Left ventricular hypertrophy (LVH) is one of the risk factors for
      cardiovascular (CV) disease and mortality. However, the relationship between
      socioeconomic status (SES) and LVH in chronic kidney disease remains unclear.
      METHODS: Data were collected from the KoreaN Cohort Study for Outcome in Patients
      With Chronic Kidney Disease (KNOW-CKD, NCT01630486 at
      http://www.clinicaltrials.gov ). Subjects with CKD and aged >=50 were included.
      SES was characterized based on monthly income and educational attainment, each of
      which was divided into three strata. LVH was defined as LV mass/height2.7 >= 47
      g/m2.7 in female and >= 50 g/m2.7 in male. Age, sex, diabetes, CKD stage, body
      mass index, blood pressure and physical activity were included as covariates.
      RESULTS: A total of 1361 patients were included. Mean age was 60.9 +/- 6.9 years,
      and 63.2% were men. Higher education level was associated with higher monthly
      income (P for trend < 0.001). The lowest education level was independently
      associated with LVH (lower than high school, adjusted odds ratio [OR] 1.485, 95%
      CI 1.069-2.063, P = 0.018; completed high school, adjusted OR 1.150, 95%
      confidence interval [CI] 0.834-1.584, P = 0.394; highest education level as the
      reference). Monthly income level was marginally associated with LVH after
      adjusting for covariates ($1500-4500, adjusted OR 1.230, 95% CI 0.866-1.748, P =
      0.247; < $1500, adjusted OR 1.471, 95% CI 1.002-2.158, P = 0.049; > $4500;
      reference). CONCLUSIONS: In the CKD population, lower SES, defined by educational
      attainment and low income level exhibited a significant association with LVH,
      respectively. Longitudinal follow-up will reveal whether lower SES is associated
      with poor CKD outcomes.

PMID- 30115014
TI  - PdumBase: a transcriptome database and research tool for Platynereis dumerilii
      and early development of other metazoans.
AB  - BACKGROUND: The marine polychaete annelid Platynereis dumerilii has recently
      emerged as a prominent organism for the study of development, evolution, stem
      cells, regeneration, marine ecology, chronobiology and neurobiology within
      metazoans. Its phylogenetic position within the spiralian/ lophotrochozoan clade,
      the comparatively high conservation of ancestral features in the Platynereis
      genome, and experimental access to any stage within its life cycle, make
      Platynereis an important model for elucidating the complex regulatory and
      functional molecular mechanisms governing early development, later organogenesis,
      and various features of its larval and adult life. High resolution RNA-seq gene
      expression data obtained from specific developmental stages can be used to
      dissect early developmental mechanisms. However, the potential for discovery of
      these mechanisms relies on tools to search, retrieve, and compare genome-wide
      information within Platynereis, and across other metazoan taxa. RESULTS: To
      facilitate exploration and discovery by the broader scientific community, we have
      developed a web-based, searchable online research tool, PdumBase, featuring the
      first comprehensive transcriptome database for Platynereis dumerilii during early
      stages of development (2 h ~ 14 h). Our database also includes additional stages
      over the P. dumerilii life cycle and provides access to the expression data of
      17,213 genes (31,806 transcripts) along with annotation information sourced from
      Swiss-Prot, Gene Ontology, KEGG pathways, Pfam domains, TmHMM, SingleP, and
      EggNOG orthology. Expression data for each gene includes the stage, the
      normalized FPKM, the raw read counts, and information that can be leveraged for
      statistical analyses of differential gene expression and the construction of
      genome-wide co-expression networks. In addition, PdumBase offers early stage
      transcriptome expression data from five further species as a valuable resource
      for investigators interested in comparing early development in different
      organisms. To understand conservation of Platynereis gene models and to validate
      gene annotation, most Platynereis gene models include a comprehensive
      phylogenetic analysis across 18 species representing diverse metazoan taxa.
      CONCLUSIONS: PdumBase represents the first online resource for the early
      developmental transcriptome of Platynereis dumerilii. It serves as a research
      platform for discovery and exploration of gene expression during early stages,
      throughout the Platynereis life cycle, and enables comparison to other model
      organisms. PdumBase is freely available at http://pdumbase.gdcb.iastate.edu .

PMID- 30115017
TI  - Lesions of "uncertain malignant potential" in the breast (B3) identified with
      mammography screening.
AB  - BACKGROUND: Core needle biopsy (CNB) is a standard diagnostic procedure in the
      setting of breast cancer screening. However, CNB may result in the borderline
      diagnoses of lesion of uncertain malignant potential (B3). The aim of this study
      was to access the outcome of lesions diagnosed as B3 category in a large series
      of screen-detected cases to evaluate the rates of malignancy for the different
      histological subtypes. METHODS: We identified all CNBs over a six-year period
      (2009-2015) in a breast cancer screening unit in Germany. A total of 8.388 CNB's
      were performed for screen detected breast lesions. B3 diagnosis comprised 4.5%
      (376/8.388). Of the 376 patients who were diagnosed as B3, 299 underwent
      subsequent excision biopsy with final excision histology. RESULTS: Out of 376
      patients diagnosed with B3 lesions, the prevalence of different histopathology
      showed 161 (42.8%) patients with atypical ductal hyperplasia (ADH), 98 (26.1%)
      with flat epithelial atypia (FEA), 50 women (13.3%) showed lobular neoplasia
      (LN), in 40 (10.6%) patients papillary findings and in 27 patients (7.2%) a
      radial scar complex. Final excision histology was benign in 74% (221/299) and
      malignant in 26% (78/299) of the patients. Lesion specific positive predictive
      values (PPV) for a subsequent diagnosis of in situ or invasive carcinoma were as
      follows: ADH 40%, FEA 20.5%, papillary lesion 13.5%, radial scar 16.6%, LN 0%.
      CONCLUSION: Our results show that approximately one-third of core needle biopsies
      of screen detected breast lesions classified as B3 are premalignant or malignant
      on excision. Lesions of uncertain malignant potential of the breast (B3) are
      heterogeneous in respect to risk of malignancy.

PMID- 30115016
TI  - Differential expression of Cosmc, T-synthase and mucins in Tn-positive colorectal
      cancers.
AB  - BACKGROUND: The Tn neoantigen (GalNAcalpha1-O-Ser/Thr) is an O-glycan expressed
      in various types of human cancers. Studies in several Tn-expressing cancer cell
      lines and pancreatic tumors have identified loss of Cosmc expression caused by
      either mutations or promoter hypermethylation. In this study, we explored the
      mechanism(s) for Tn expression in human colorectal cancers (CRC). METHODS: Tn
      expressing cell populations were isolated from CRC cell lines by Fluorescence
      associated cell sorting (FACS). The expression of the Tn and sialylated Tn (STn)
      antigens, Cosmc, T-synthase, and mucins was characterized in paired specimens
      with CRC and in CRC cell lines by immunostaining, western blot, and qPCR.
      RESULTS: Using well-defined monoclonal antibodies, we confirmed prevalent Tn/STn
      expression in CRC samples. However, a majority of these tumors had elevated T
      synthase activity and expression of both Cosmc and T-synthase proteins.
      Meanwhile, Tn antigen expression was not caused by mucin overproduction. In
      addition, we found that Tn-expressing CRC cell lines had either loss-of-function
      mutations in Cosmc or reversible Tn antigen expression, which was not caused by
      the deficiency of T-synthase activity. CONCLUSIONS: Our results demonstrate
      multiple mechanisms for Tn expression in CRCs.

PMID- 30115018
TI  - Planning for an uncertain future in progressive neurological disease: a
      qualitative study of patient and family decision-making with a focus on eating
      and drinking.
AB  - BACKGROUND: Dysphagia and other eating and drinking difficulties are common in
      progressive neurological diseases. Mealtimes can become a major source of
      difficulty and anxiety for patients and their families. Decisions about eating,
      drinking and care can become challenging as disease progresses, and the person in
      question loses the capacity to participate in decisions about their own care. We
      sought to investigate how patients and their family members make decisions about
      their future care as their condition deteriorates, with a particular focus on
      mealtimes, eating and drinking. METHODS: Longitudinal qualitative in-depth
      interviews were undertaken with patients and their family members (N = 29) across
      a range of disease groups, including: dementia, Parkinson's Disease, Huntington's
      Disease, Progressive Supranuclear Palsy, Motor Neurone Disease, Multiple
      Sclerosis. Patients had varying degrees of eating and drinking difficulties, and
      levels of decision-making capacity. Interviews were 'participant led' and
      undertaken in the patients' own homes or a place of their choosing. Follow-up
      interviews were three months to one year later depending upon disease trajectory.
      Interviews were audio recorded and analysed in NVivo using a Thematic Analysis
      approach. RESULTS: Twenty-nine participants were interviewed between 2015 and
      2017. Two key themes emerged from the analysis: 1) Health Literacy: the extent to
      which patients and relatives appeared to know about the condition and its
      treatment. Patients and their family members varied in their ability to speak and
      communicate about their condition and prognosis. 2) Planning style: the extent to
      which participants appeared to value involvement in advance care-planning.
      Patients and their family members varied in the way in which they made decisions:
      some preferred to 'take each day as it comes', while others wished to plan
      extensively for the future. CONCLUSIONS: Issues with eating and drinking are
      often overlooked. Clinicians need to understand both the patient's level of
      health literacy and their style of planning before communicating with patients
      and their families about these sensitive issues.

PMID- 30115019
TI  - Engaging pregnant women in observational research: a qualitative exploratory
      study.
AB  - BACKGROUND: Recruitment of pregnant women to population health research can be
      challenging, especially if the research topic is sensitive. While many pregnant
      women may be inherently interested in research about pregnancy, there is the
      possibility that the nature and timing of the project may give rise to anxiety in
      some women, especially if the topic is sensitive or it brings about new awareness
      of potential pregnancy complications. Research staff undertaking recruitment need
      to be skilled at strategies to manage the environment, and have well developed
      communication and interpersonal skills to explain and promote the study and
      facilitate each woman's informed decision-making regarding participation.
      However, the skills needed by recruitment staff to successfully engage pregnant
      women with a research topic are not well understood. This study aimed to address
      this evidence gap by providing insight into the dynamics between a pregnant woman
      and recruitment staff at the time of the offer to participate in an observational
      study about alcohol use in pregnancy. METHODS: Naturalistic inquiry guided a
      qualitative exploratory descriptive approach. Experienced recruitment staff from
      the Asking Questions about Alcohol in Pregnancy (AQUA) study (Muggli et al., BMC
      Pregnancy Childbirth 14:302, 2014) participated in individual semi-structured
      interviews and were asked about their experiences and approaches to engaging
      pregnant women. Interviews were transcribed verbatim and analysed using inductive
      content analysis. RESULTS: Pregnant women brought with them an inherent interest
      or disinterest in alcohol research, or in research in general, which formed the
      basis for engagement. Women responded favourably to the invitation to participate
      being delivered without pressure, and as part of a two-way conversation.
      Engagement with a sensitive topic such as alcohol use in pregnancy was
      facilitated by a non-judgmental and non-targeted approach. Influences such as
      privacy, distractions, partner's opinion, time factors and level of clinical
      support either facilitated or hindered a woman's engagement with the research.
      CONCLUSIONS: These results provide an in-depth explanation of barriers and
      enablers to recruitment of pregnant women in antenatal clinics to studies that
      may inform strategies and the training of recruitment staff.

PMID- 30115020
TI  - Do fragments and glycosylated isoforms of alpha-1-antitrypsin in CSF mirror
      spinal pathophysiological mechanisms in chronic peripheral neuropathic pain? An
      exploratory, discovery phase study.
AB  - BACKGROUND: Post-translational modifications (PTMs) generate a tremendous protein
      diversity from the ~ 20,000 protein-coding genes of the human genome. In chronic
      pain conditions, exposure to pathological processes in the central nervous system
      could lead to disease-specific PTMs detectable in the cerebrospinal fluid (CSF).
      In a previous hypothesis-generating study, we reported that seven out of 260 CSF
      proteins highly discriminated between neuropathic pain patients and healthy
      controls: one isoform of angiotensinogen (AG), two isoforms of alpha-1
      antitrypsin (AT), three isoforms of haptoglobin (HG), and one isoform of pigment
      epithelium-derived factor (PEDF). The present study had three aims: (1) To
      examine the multivariate inter-correlations between all identified isoforms of
      these seven proteins; (2) Based on the results of the first aim, to characterize
      PTMs in a subset of interesting proteins; (3) To regress clinical pain data using
      the 260 proteins as predictors, thereby testing the hypothesis that the above
      mentioned seven discriminating proteins and/or the characterized
      isoforms/fragments of aim (2) would be among the proteins having the highest
      predictive power for clinical pain data. METHODS: CSF samples from 11 neuropathic
      pain patients and 11 healthy controls were used for biochemical analysis of
      protein isoforms. PTM characterization was performed using enzymatic reaction
      assay and mass spectrometry. Multivariate data analysis (principal component
      analysis and orthogonal partial least square regression) was applied on the
      quantified protein isoforms. RESULTS: We identified 5 isoforms of AG, 18 isoforms
      of AT, 5 isoforms of HG, and 5 isoforms of PEDF. Fragments and glycosylated
      isoforms of AT were studied in depth. When regressing the pain intensity data of
      patients, three isoforms of AT, two isoforms of PEDF, and one isoform of
      angiotensinogen "reappeared" as major results, i.e., they were major findings
      both when comparing patients with healthy controls and when regressing pain
      intensity in patients. CONCLUSIONS: Altered levels of fragments and/or
      glycosylated isoforms of alpha-1-antitrypsin might mirror pathophysiological
      processes in the spinal cord of neuropathic pain patients. In particular, we
      suggest that a putative disease-specific combination of the levels of two
      different N-truncated fragments of alpha-1-antitrypsin might be interesting for
      future CSF and/or plasma biomarker investigations in chronic neuropathic pain.

PMID- 30115023
TI  - Impact of childhood trauma on sensory gating in patients with first-episode
      schizophrenia.
AB  - BACKGROUND: Childhood trauma (CT) has been found to contribute to the onset of
      schizophrenia and auditory sensory gating deficit is a leading endophenotype for
      schizophrenia. However, the association between the CT and sensory gating in
      first-episode schizophrenia remains elusive. METHODS: Fifty-six patients and 49
      age and sex-matched healthy controls were assessed using the Childhood Trauma
      Questionnaire-Short Form (CTQ-SF) for CT and Positive and Negative Syndrome Scale
      (PANSS) for symptoms severity. Sensory gating was tested using the modified
      paradigm, perceived spatial separation-induced prepulse inhibition (PSS-PPI), and
      the perceived spatial co-location PPI (PSC-PPI or classical PPI). RESULTS:
      Comparing with healthy controls, the patients had significantly higher score on
      sexual abuse (t = 2.729, p < 0.05), lower PSS- PPI, % (ISI = 120 ms and ISI = 60
      ms) (t = - 3.089, - 4.196, p < 0.05). Univariate analysis revealed the absence of
      a significant correlation among CT, PPI paradigms and symptoms. However, multiple
      linear regression analyses demonstrated the CTQ-SF total was negatively
      associated with PSS PPI (ISI = 120 ms) (p = 0.018). CONCLUSION: The current study
      illustrates that the impact of CT on sensory gating in patients with first
      episode schizophrenia, and thus we conclude that CT may be a risk factor to the
      occurrence of schizophrenia through its impact on sensory gating.

PMID- 30115021
TI  - Wearables for gait and balance assessment in the neurological ward - study design
      and first results of a prospective cross-sectional feasibility study with 384
      inpatients.
AB  - BACKGROUND: Deficits in gait and balance are common among neurological
      inpatients. Currently, assessment of these patients is mainly subjective. New
      assessment options using wearables may provide complementary and more objective
      information. METHODS: In this prospective cross-sectional feasibility study
      performed over a four-month period, all patients referred to a normal neurology
      ward of a university hospital and aged between 40 and 89 years were asked to
      participate. Gait and balance deficits were assessed with wearables at the ankles
      and the lower back. Frailty, sarcopenia, Parkinsonism, depression, quality of
      life, fall history, fear of falling, physical activity, and cognition were
      evaluated with questionnaires and surveys. RESULTS: Eighty-two percent (n = 384)
      of all eligible patients participated. Of those, 39% (n = 151) had no gait and
      balance deficit, 21% (n = 79) had gait deficits, 11% (n = 44) had balance
      deficits and 29% (n = 110) had gait and balance deficits. Parkinson's disease,
      stroke, epilepsy, pain syndromes, and multiple sclerosis were the most common
      diseases. The assessment was well accepted. CONCLUSIONS: Our study suggests that
      the use of wearables for the assessment of gait and balance features in a
      clinical setting is feasible. Moreover, preliminary results confirm previous
      epidemiological data about gait and balance deficits among neurological
      inpatients. Evaluation of neurological inpatients with novel wearable technology
      opens new opportunities for the assessment of predictive, progression and
      treatment response markers.

PMID- 30115022
TI  - Galectin 3 expression in regional lymph nodes and lymph node metastases of oral
      squamous cell carcinomas.
AB  - BACKGROUND: Neck dissection is standard in surgical management of oral squamous
      cell carcinomas (oscc). However, the immunologic link between primary tumor and
      lymph nodes is insufficiently understood. Galectin 3 (Gal3) promotes M2
      polarization of macrophages and contributes to immunosuppression. The current
      study analyzes the association between Gal3 expression in regional lymph nodes of
      oscc with histomorphologic parameters (T-, N-, L- Pn-stage, grading) of the
      primary tumor. Additionally, Gal3 expression is correlated with markers of
      macrophage polarization (M1 vs. M2). METHODS: Preoperative diagnostic biopsies (n
      = 26), tumor resection specimens (n = 34), tumor-free lymph nodes (n = 28) and
      lymph node metastases (n = 10) of T1/T2 oscc patients were immunohistochemically
      analyzed for Gal3 and macrophage marker (CD68, CD11c, CD163 and MRC1) expression.
      The number of positive cells and the expression ratios were quantitatively
      assessed. RESULTS: High Gal3 expression in tumor-free regional lymph nodes was
      significantly (p < 0.05) associated with increased tumor size. The epithelial
      compartment of lymph node metastases showed a significantly (p < 0.05) increased
      Gal3 expression compared to biopsies and tumor resection specimens. Cell density
      of M2 macrophages was significantly (p < 0.05) and positively correlated with the
      number of Gal3 expressing cells in lymph nodes and tumor specimens. CONCLUSION:
      Gal3 expression in regional lymph nodes might be associated with oscc
      progression. The increased Gal3 expression in regional lymph nodes of larger
      tumors underlines the need of immunomodulatory treatment concepts in early-stage
      oscc. Blocking of Gal3 might be a therapeutic option in oral cancer.

PMID- 30115024
TI  - Assessment of meibomian glands using a custom-made meibographer in dry eye
      patients in Ghana.
AB  - BACKGROUND: Meibomian Gland Dysfunction (MGD) is a leading cause of evaporative
      Dry Eye Disease (DED). This makes non-invasive meibography an important procedure
      in the clinical evaluation of DED patients. Our purpose was to conduct a lead-off
      investigation focused on the practicality of performing meibography in a
      developing country, with limited access to complex ophthalmic imaging systems,
      using a custom meibographer, as a step to future comparative studies on meibomian
      glands and DED in Africa. METHODS: Meibomian glands(MG) in 76 upper eyelids (UL)
      and 49 lower eyelids (LL) in 1 eye each of 125 patients randomly selected from a
      patient population presenting with subjective DED symptoms at a clinic were
      photographed using a custom meibographer. Single frames were captured, and the MG
      area determined by intensity threshold segmentation and area calculation using
      Image J software. MG loss (MGL) was quantified by outlining its area and
      expressing it as a percentage of the total MG per Pult's grading scheme. Dry eye
      measures included Tear Film Break Up - Time (TUBT), Schirmer's test and Ocular
      Surface Staining (OSS). Symptoms were evaluated using the SPEED II questionnaire.
      Correlations between MGL and age, ocular signs and symptoms were analyzed by
      Pearson's. Differences between comparable groups were analyzed by Mann - Whitney
      test; p < 0.05 was considered significant. RESULTS: Overall mean MGL was 32.10%
      +/- 25.0% (26.25% +/- 22.40% for UL and 40.33% +/- 26.70% for LL). MGL correlated
      significantly with age [r = 0.91, p = 0.001], SPEED scores [r = 0.90, p = 0.001],
      OSS [r = 0.75, p = 0.001] and TBUT [r = - 0.81, p = 0.001]. MGL scores were
      significantly higher in the UL than LL [U = 1293.5 p = 0.004]. CONCLUSION: This
      study for the first time presents data on the status of Meibomian glands in
      Africa. It furthermore suggests that it is feasible to examine Meibomian glands
      using a custom meibographer in developing countries with limited access to
      complex imaging systems. It also demonstrates the benefit and cost-effectiveness
      of a simple device by the observed significant relations between meibomian gland
      loss and DED in these patients.

PMID- 30115025
TI  - Gefitinib successfully administered in a lung cancer patient with leptomeningeal
      carcinomatosis after erlotinib-induced pneumatosis intestinalis.
AB  - BACKGROUND: Pneumatosis intestinalis (PI) is a rare complication of chemotherapy,
      characterized by multiple gas accumulations within the bowel wall. CASE
      PRESENTATION: A 71-year-old woman with epidermal growth factor receptor (EGFR)
      mutation-positive lung adenocarcinoma was admitted to our hospital because of
      reduced consciousness. She was diagnosed as having leptomeningeal carcinomatosis
      (LM) using lumbar puncture. Because she could not swallow a tablet, erlotinib was
      administered via a feeding tube. Her state of consciousness gradually improved,
      but she experienced diarrhea several times a day. After 3 weeks of erlotinib
      therapy, PI occurred. Erlotinib was discontinued and PI was resolved after
      treatment with conservative therapies. Erlotinib was re-administrated and PI
      occurred again. After improvement of erlotinib-induced PI, gefitinib was
      administered by a feeding tube and the patient did not experience PI or diarrhea.
      The patient survived 8 months from the diagnosis of LM. CONCLUSION: PI is one of
      the side effects of erlotinib, and consecutive therapies are useful for the
      treatment of PI. In this patient, gefitinib was successfully administered after
      erlotinib-induced PI.

PMID- 30115026
TI  - Simultaneous detection of lung fusions using a multiplex RT-PCR next generation
      sequencing-based approach: a multi-institutional research study.
AB  - BACKGROUND: Gene fusion events resulting from chromosomal rearrangements play an
      important role in initiation of lung adenocarcinoma. The recent association of
      four oncogenic driver genes, ALK, ROS1, RET, and NTRK1, as lung tumor predictive
      biomarkers has increased the need for development of up-to-date technologies for
      detection of these biomarkers in limited amounts of material. METHODS: We
      describe here a multi-institutional study using the Ion AmpliSeqTM RNA Fusion
      Lung Cancer Research Panel to interrogate previously characterized lung tumor
      samples. RESULTS: Reproducibility between laboratories using diluted fusion
      positive cell lines was 100%. A cohort of lung clinical research samples from
      different origins (tissue biopsies, tissue resections, lymph nodes and pleural
      fluid samples) were used to evaluate the panel. We observed 97% concordance for
      ALK (28/30 positive; 71/70 negative samples), 95% for ROS1 (3/4 positive; 19/18
      negative samples), and 93% for RET (2/1 positive; 13/14 negative samples) between
      the AmpliSeq assay and other methodologies. CONCLUSION: This methodology enables
      simultaneous detection of multiple ALK, ROS1, RET, and NTRK1 gene fusion
      transcripts in a single panel, enhanced by an integrated analysis solution. The
      assay performs well on limited amounts of input RNA (10 ng) and offers an
      integrated single assay solution for detection of actionable fusions in lung
      adenocarcinoma, with potential savings in both cost and turn-around-time compared
      to the combination of all four assays by other methods.

PMID- 30115027
TI  - Low serum gastrin associated with ER+ breast cancer development via inactivation
      of CCKBR/ERK/P65 signaling.
AB  - BACKGROUND: Gastrin is an important gastrointestinal hormone produced primarily
      by G-cells in the antrum of the stomach. It normally regulates gastric acid
      secretion and is implicated in a number of human disease states, but how its
      function affects breast cancer (BC) development is not documented. The current
      study investigated the suppressive effects of gastrin on BC and its underlying
      mechanisms. METHODS: Serum levels of gastrin were measured by enzyme-linked
      immunosorbent assay (ELISA) and correlation between gastrin level and development
      of BC was analyzed by chi-square test. Inhibitory effects of gastrin on BC were
      investigated by CCK-8 assay and nude mice models. Expressions of CCKBR/ERK/P65 in
      BC patients were determined through immunohistochemistry (IHC) and Western blot.
      Survival analysis was performed using the log-rank test. RESULTS: The results
      indicated that the serum level of gastrin in BC patients was lower compared with
      normal control. Cellular and molecular experiments indicated that reduction of
      gastrin is associated with inactivation of cholecystokinin B receptor
      (CCKBR)/ERK/P65 signaling in BC cells which is corresponding to molecular type of
      estrogen receptor (ER) positive BC. Furthermore, we found that low expression of
      gastrin/CCKBR/ERK /P65 was correlated to worse prognosis in BC patients. Gastrin
      or ERK/P65 activators inhibited ER+ BC through CCKBR-mediated activation of
      ERK/P65. Moreover, combination treatment with gastrin and tamoxifen more
      efficiently inhibited ER+ BC than tamoxifen alone. CONCLUSIONS: We concluded that
      low serum gastrin is related to increased risk of ER+ BC development. The results
      also established that CCKBR/ERK/P65 signaling function is generally tumor
      suppressive in ER+ BC, indicating therapies should focus on restoring, not
      inhibiting, CCKBR/ERK/P65 pathway activity.

PMID- 30115029
TI  - Increased risk of deep vein thrombosis in end-stage renal disease patients.
AB  - BACKGROUND: Previous studies have shown that chronic kidney disease increases the
      risk of deep vein thrombosis (DVT). DVT is the risk of pulmonary embolism among
      persons with end-stage renal disease (ESRD). Information on the incidence of DVT
      in ESRD is limited, and no studies have been conducted in the Asian population.
      The aim of our study was to investigate the incidence of DVT in Asian ESRD
      patients by comparing with the non-ESRD patients and to identify the associated
      risk factors. METHODS: This study retrieved patients who were diagnosed with ESRD
      (ICD-9-CM codes 585 or 586) between January 1, 2004, and December 31, 2010, from
      the National Health Insurance Research Database in Taiwan. All ESRD patients had
      received a catastrophic illness card from the Ministry of Health and Welfare in
      Taiwan, with the major illness identified as ESRD. Patients who had DVT before
      the index date or who had incomplete records were excluded from the analysis. A
      total of 4865 ESRD patients were enrolled. There are 3564 ESRD patients included
      after exclusion of patients with previous DVT and patients with incomplete
      records. The control subjects were randomly selected as the patients without ESRD
      by matching study subjects according to age (+/-3 years), gender, and the year of
      admission at a 2:1 ratio from the same dataset. RESULTS: The incidence rate of
      DVT was substantially higher in the ESRD group than in the without-ESRD group
      (20.9 vs. 1.46 per 10^4 person-years). The adjusted hazard ratio (aHR 13.92; 95%
      CI 9.25-20.95) of DVT for the ESRD patients was 13.92 times that for the non-ESRD
      patients. ESRD patients older than 50 years had a higher risk of DVT (aHR 1.65;
      95% CI 1.13-2.40; P = 0.01). Hyperlipidemia was significantly associated with an
      increased risk of DVT (aHR 1.73; 95% CI 1.08-2.78; P = 0.02). ESRD patients with
      three or more comorbidities were substantially more likely to have DVT (aHR 1.45;
      95% CI 1.03-2.03; P = 0.03). CONCLUSIONS: ESRD patients had a higher risk of DVT
      than non-ESRD patients. Among the ESRD patients, being older than 50 years and
      having dyslipidemia increased the risk of DVT.

PMID- 30115028
TI  - Value-based evaluation of dialysis versus conservative care in older patients
      with advanced chronic kidney disease: a cohort study.
AB  - BACKGROUND: Conservative care is argued to be a reasonable treatment alternative
      for dialysis in older patients with advanced chronic kidney disease (CKD).
      However, comparisons are scarce and generally focus on survival only. Comparative
      data on more patient-relevant outcomes are needed to truly foster shared decision
      making on an individual level, and cost comparison is needed to assess value of
      care. METHODS: We conducted a retrospective observational single-center cohort
      study in 366 patients aged >=70 years with advanced CKD, who chose dialysis (n =
      240) or conservative care (n = 126) after careful counselling by a
      multidisciplinary team in a non-academic teaching hospital in The Netherlands.
      Using a value-based health care approach (value = outcomes/cost): survival,
      health-related quality of life-cross-sectionally assessed with the Kidney Disease
      Quality of Life Short FormTM-treatment burden, and treatment costs were
      evaluated. RESULTS: The overall survival benefit of patients on a dialysis
      pathway compared with patients on conservative care diminished or lost
      significance in patients aged >=80 years or with severe comorbidity. There were
      no differences between patients managed conservatively and dialysis patients on
      physical and mental health summary scores (all P > 0.1). Patients on conservative
      care had 352.7 hospital free days per year versus 282.7 in patients on a dialysis
      pathway, calculated from treatment decision (adjusted incidence rate ratio: 1.15,
      95% confidence interval: 1.09 to 1.21, P <  0.001). Annual treatment costs were
      lower in patients on conservative care (adjusted cost ratio: 0.43, 95% confidence
      interval: 0.28 to 0.67, P <  0.001). CONCLUSIONS: In this study, conservative
      care is shown to be a viable treatment option in older patients with advanced
      CKD, particularly in the oldest old and those with severe comorbidity. By
      achieving similar outcomes at lower treatment burden and treatment costs, value
      was generated for older patients choosing conservative care and society.

PMID- 30115031
TI  - Effect of the menstrual cycle on circulation during combined spinal-epidural
      anaesthesia.
AB  - BACKGROUND: From adolescence to menopause, hormone levels during the menstrual
      cycle affect various body systems, from the cardiovascular system to the water
      and electrolyte balance. This study investigated the effect of different phases
      of the menstrual cycle on circulatory function relative to changes in body
      position and combined spinal-epidural anaesthesia (CSEA). METHODS: Forty-six
      women were selected who underwent scheduled gynaecological surgery, were
      classified as American Society of Anesthesiology (ASA) I-II, and met the test
      criteria. The sample was divided into the follicular and corpus luteal groups.
      Preoperative heart rate and blood pressure measurements were taken from the
      supine and standing positions. Heart rate measurements as well as systolic,
      diastolic, and mean blood pressure measurements were taken upon entering the
      operating room, at the beginning of the spinal-epidural anaesthesia, and 10, 20,
      and 30 min after anaesthesia was administered. RESULTS: The heart rates of
      patients in the corpus luteal group were higher than those of patients in the
      follicular group both before and after anaesthesia (P <  0.05). Significantly
      more ephedrine was used during the first 30 min of CSEA in the corpus luteal
      group than in the follicular group (P <  0.05). CONCLUSIONS: Although the effect
      was slight, women in the follicular phase were better able to compensate and
      tolerate circulatory fluctuations than those in the luteal phase.

PMID- 30115030
TI  - Construction of high-density linkage maps for mapping quantitative trait loci for
      multiple traits in field pea (Pisum sativum L.).
AB  - BACKGROUND: The objective of this research was to map quantitative trait loci
      (QTLs) of multiple traits of breeding importance in pea (Pisum sativum L.). Three
      recombinant inbred line (RIL) populations, PR-02 (Orb x CDC Striker), PR-07
      (Carerra x CDC Striker) and PR-15 (1-2347-144 x CDC Meadow) were phenotyped for
      agronomic and seed quality traits under field conditions over multiple
      environments in Saskatchewan, Canada. The mapping populations were genotyped
      using genotyping-by-sequencing (GBS) method for simultaneous single nucleotide
      polymorphism (SNP) discovery and construction of high-density linkage maps.
      RESULTS: After filtering for read depth, segregation distortion, and missing
      values, 2234, 3389 and 3541 single nucleotide polymorphism (SNP) markers
      identified by GBS in PR-02, PR-07 and PR-15, respectively, were used for
      construction of genetic linkage maps. Genetic linkage groups were assigned by
      anchoring to SNP markers previously positioned on these linkage maps. PR-02, PR
      07 and PR-15 genetic maps represented 527, 675 and 609 non-redundant loci, and
      cover map distances of 951.9, 1008.8 and 914.2 cM, respectively. Based on
      phenotyping of the three mapping populations in multiple environments, 375 QTLs
      were identified for important traits including days to flowering, days to
      maturity, lodging resistance, Mycosphaerella blight resistance, seed weight,
      grain yield, acid and neutral detergent fiber concentration, seed starch
      concentration, seed shape, seed dimpling, and concentration of seed iron,
      selenium and zinc. Of all the QTLs identified, the most significant in terms of
      explained percentage of maximum phenotypic variance (PVmax) and occurrence in
      multiple environments were the QTLs for days to flowering (PVmax = 47.9%), plant
      height (PVmax = 65.1%), lodging resistance (PVmax = 35.3%), grain yield (PVmax =
      54.2%), seed iron concentration (PVmax = 27.4%), and seed zinc concentration
      (PVmax = 43.2%). CONCLUSION: We have identified highly significant and
      reproducible QTLs for several agronomic and seed quality traits of breeding
      importance in pea. The QTLs identified will be the basis for fine mapping
      candidate genes, while some of the markers linked to the highly significant QTLs
      are useful for immediate breeding applications.

PMID- 30115032
TI  - How many patients are required to provide a high level of reliability in the
      Japanese version of the CARE Measure? A secondary analysis.
AB  - BACKGROUND: Empathy is widely regarded as being key to effective consultation in
      general practice. The Consultation and Relational Empathy (CARE) Measure is a
      widely used and well-validated patient-rated measure in English. A Japanese
      version of the CARE Measure has undergone preliminary validation, but its ability
      to differentiate between individual doctors has not been established. The current
      study sought to investigate the reliability of the Japanese version of the CARE
      Measure in terms of discrimination between doctors. METHODS: We conducted
      secondary analysis of a dataset involving 252 patients assessed by nine attending
      General Practitioners. The intra-cluster correlation coefficient was evaluated as
      an index of the reliability of the Japanese version of the CARE Measure for
      discriminating between doctors. With a criterion of intra-cluster correlation
      coefficient = 0.8, we conducted a decision (D) study using generalizability
      theory to determine the required number of patients for reliable CARE Measure
      estimates. RESULTS: The ability of the CARE Measure to discriminate between
      doctors increased with the number of patients assessed per doctor. A sample size
      of 38 or more patients provided an average intra-cluster correlation coefficient
      of 0.8. CONCLUSIONS: The Japanese CARE Measure appears to reliably discriminate
      between doctors with a feasible number of patient-ratings per doctor. Further
      studies involving larger numbers of doctors with a multicenter analysis are
      required to confirm the results of the current study, which was conducted at a
      single institution.

PMID- 30115033
TI  - Exceptional association of two species of bacteria causing mediastinitis:
      Haemophilus influenzae (H. influenzae) and Aggregatibacter aphrophilus (A.
      aphrophilus).
AB  - BACKGROUND: Post cardiac surgery mediastinitis is the major infectious
      complication, despite the development of surgical techniques and the application
      of strict preventive measures. The Haemophilus influenzae mediastinitis is very
      rare. The mediastinitis caused by the association between Haemophilus influenzae
      and Aggregatibacter aphrophilus has never been described to our knowledge. CASE
      PRESENTATION: We report the case of an exceptional combination of Haemophilus
      influenzae and Aggregatibacter aphrophilus in a patient operated for single
      bypass which is complicated by mediastinitis the 10th day after the surgical act.
      CONCLUSION: The conclusion to be drawn from this work is to think in unusual
      seeds in case of mediastinitis post cardiac surgery for the elaboration of
      recommendations for antibiotic prophylaxis.

PMID- 30115036
TI  - The Interdialytic Creatinine Rise is a novel marker of volume overload and
      mortality risk in hemodialysis patients.
AB  - BACKGROUND: Volume overload poses a major risk in hemodialysis patients but
      simple detection methods are lacking. We propose a novel marker, the
      Interdialytic Creatinine Rise (IDCR), readily calculated as the change in serum
      creatinine over time (in mg/dL/h), to assess volume overload and predict
      mortality risk in hemodialysis patients. METHODS: First, we calculated IDCR
      changes with volume in a prospective cohort of 35 hospitalized hemodialysis
      patients awaiting hemodialysis and 33 hospitalized patients undergoing
      hemodialysis every other day. Second, in a prospective cohort of 25 outpatients,
      IDCR cutoff values associated with hypervolemia were determined between two
      treatments and compared with simultaneous volume assessments by their
      nephrologist. Third, IDCR as a mortality predictor was studied using survival
      analysis in a longitudinal retrospective cohort study of 39 maintenance
      hemodialysis patients followed from 2012 until death or 2017. RESULTS: IDCR
      decreased by - 0.014 mg/dL/h each day (95%CI - 0.017,- 0.010; p < 0.001) without
      dialysis due to fluid volume gain and increased by 0.013 mg/dL/h (95%CI
      0.008,0.017; p < 0.001) from before to after each successive hemodialysis due to
      fluid removal. Choosing an IDCR cutoff value of <=0.1 had sensitivity of 82% and
      specificity of 79% in diagnosing volume overload with the area under the ROC
      curve of 0.78 (95%CI 0.59,0.97). The hazard ratio of death for each 0.01 decrease
      in IDCR was 1.64 (95%CI 1.31,2.07; p < 0.001). If IDCR decreased to less than
      0.05 mg/dL/h, the median survival was 32 days and the odds ratio of death within
      2 months was 38 (95%CI 8, 131; p < 0.001). CONCLUSIONS: In this pilot study, IDCR
      is shown to be a novel metric that decreases with fluid retention and increases
      after fluid removal. IDCR can assist clinicians in detection or exclusion of
      volume overload in hemodialysis patients and provide prognostic value in
      identifying those at high risk for death.

PMID- 30115037
TI  - The effect of a voucher incentive on a survey response rate in the clinical
      setting: a quasi-randomized controlled trial.
AB  - BACKGROUND: Financial rewards have been shown to be an important motivator to
      include normal healthy volunteers in trials. Less emphasis has been put on non
      healthy volunteers. No previous study has investigated the impact of a voucher
      incentive for participants in a cross-sectional study in a clinical setting. The
      objective of this study was to examine the impact of a small voucher incentive on
      a survey response rate in a clinical setting at the point-of-care in a quasi
      randomized controlled trial (q-RCT). METHODS: This was an ancillary study to a
      survey of patients subsequent to their appointment with a physician investigating
      physician-patient communication. We randomized participants to receive or not
      receive a voucher for a coffee (costs: 1 ?) enclosed in the survey package.
      Alternation of groups was performed on a weekly basis. The exact Chi-square test
      was used to compare response rates between study arms. RESULTS: In total, 472
      participants received the survey package. Among them, 249 participants were quasi
      randomized to the voucher arm and 223 to the control group. The total response
      rate was 46%. The response rates were 48% in the voucher arm and 44% in the
      control group. The corresponding risk ratio was 1.09 (95% CI: 0.89, 1.32).
      CONCLUSIONS: A small voucher incentive to increase the response rate in a survey
      investigating physician-patient communication was unlikely to have an impact. It
      can be speculated whether the magnitude of the voucher was too low to generate an
      impact. This should be further investigated in future real-world studies.

PMID- 30115034
TI  - Genomic regions underlying uniformity of yearling weight in Nellore cattle
      evaluated under different response variables.
AB  - BACKGROUND: In livestock, residual variance has been studied because of the
      interest to improve uniformity of production. Several studies have provided
      evidence that residual variance is partially under genetic control; however, few
      investigations have elucidated genes that control it. The aim of this study was
      to identify genomic regions associated with within-family residual variance of
      yearling weight (YW; N = 423) in Nellore bulls with high density SNP data, using
      different response variables. For this, solutions from double hierarchical
      generalized linear models (DHGLM) were used to provide the response variables, as
      follows: a DGHLM assuming non-null genetic correlation between mean and residual
      variance (rmv ? 0) to obtain deregressed EBV for mean (dEBVm) and residual
      variance (dEBVv); and a DHGLM assuming rmv = 0 to obtain two alternative response
      variables for residual variance, dEBVv_r0 and log-transformed variance of
      estimated residuals (ln_[Formula: see text]). RESULTS: The dEBVm and dEBVv were
      highly correlated, resulting in common regions associated with mean and residual
      variance of YW. However, higher effects on variance than the mean showed that
      these regions had effects on the variance beyond scale effects. More independent
      association results between mean and residual variance were obtained when null
      rmv was assumed. While 13 and 4 single nucleotide polymorphisms (SNPs) showed a
      strong association (Bayes Factor > 20) with dEBVv and ln_[Formula: see text],
      respectively, only suggestive signals were found for dEBVv_r0. All overlapping 1
      Mb windows among top 20 between dEBVm and dEBVv were previously associated with
      growth traits. The potential candidate genes for uniformity are involved in
      metabolism, stress, inflammatory and immune responses, mineralization, neuronal
      activity and bone formation. CONCLUSIONS: It is necessary to use a strategy like
      assuming null rmv to obtain genomic regions associated with uniformity that are
      not associated with the mean. Genes involved not only in metabolism, but also
      stress, inflammatory and immune responses, mineralization, neuronal activity and
      bone formation were the most promising biological candidates for uniformity of
      YW. Although no clear evidence of using a specific response variable was found,
      we recommend consider different response variables to study uniformity to
      increase evidence on candidate regions and biological mechanisms behind it.

PMID- 30115035
TI  - PIK3CA mutation is a favorable prognostic factor in esophageal cancer: molecular
      profile by next-generation sequencing using surgically resected formalin-fixed,
      paraffin-embedded tissue.
AB  - BACKGROUND: Practical and reliable genotyping procedures with a considerable
      number of samples are required not only for risk-adapted therapeutic strategies,
      but also for stratifying patients into future clinical trials for molecular
      targeting drugs. Recent advances in mutation testing, including next-generation
      sequencing, have led to the increased use of formalin-fixed paraffin-embedded
      tissue. We evaluated gene alteration profiles of cancer-related genes in
      esophageal cancer patients and correlated them with clinicopathological features,
      such as smoking status and survival outcomes. METHODS: Surgically resected
      formalin-fixed, paraffin-embedded tissue was collected from 135 consecutive
      patients with esophageal cancer who underwent esophagectomy. Based on the
      assessment of DNA quality with a quantitative PCR-based assay, uracil DNA
      glycosylase pretreatment was performed to ensure quality and accuracy of amplicon
      based massively parallel sequencing. Amplicon-based massively parallel sequencing
      was performed using the Illumina TruSeq(r) Amplicon Cancer Panel. Gene
      amplification was detected by quantitative PCR-based assay. Protein expression
      was determined by automated quantitative fluorescent immunohistochemistry.
      RESULTS: Data on genetic alterations were available for 126 patients. The median
      follow-up time was 1570 days. Amplicon-based massively parallel sequencing
      identified frequent gene alterations in TP53 (66.7%), PIK3CA (13.5%), APC
      (10.3%), ERBB4 (7.9%), and FBXW7 (7.9%). There was no association between
      clinicopathological features or prognosis with smoking status. Multivariate
      analyses revealed that the PIK3CA mutation and clinical T stage were independent
      favorable prognostic factors (hazard ratio 0.34, 95% confidence interval: 0.12
      0.96, p = 0.042). PIK3CA mutations were significantly associated with APC
      alterations (p = 0.0007) and BRAF mutations (p = 0.0090). CONCLUSIONS: Our study
      provided profiles of cancer-related genes in Japanese patients with esophageal
      cancer by next-generation sequencing using surgically resected formalin-fixed,
      paraffin-embedded tissue, and identified the PIK3CA mutation as a favorable
      prognosis biomarker.

PMID- 30115038
TI  - Perception of Beninese on intimate partner violence: evidence from 2011-2012
      Benin demographic health survey.
AB  - BACKGROUND: Violence against women remains an important issue of inequality in
      African societies, with several consequences to health, social and economic
      status. This study aims to identify the factors related to the perception of
      intimate partner violence in Benin. METHODS: Data on intimate partner violence
      was collected by conducting live interviews, and from the Benin Demographic and
      Health Survey 2012. The dependent variable was acceptance of intimate partner
      violence. The independent variables were socio-demographic features such as age,
      level of education, matrimonial status, ethnicity, religion, place of residence
      and the index of economic well-being. Logistic regressions were performed and
      odds ratios (OR) with a confidence interval of 95% (CI95%) were estimated.
      RESULTS: Among the 21,574 people who answered the questions relating to violence
      against women by an intimate partner, the prevalence of acceptance of intimate
      partner violence was 15.77%. Ethnicity, level of education, administrative
      department of residence, religion, and socio-economic quintile were factors
      associated with the respondents' acceptance of violence against women by an
      intimate partner. CONCLUSION: Acceptance of intimate partner violence could be a
      major obstacle to the success of some health programs. There is a need to break
      the norms that support the vulnerability of women in Beninese society.

PMID- 30115039
TI  - Attachment, mentalisation and expressed emotion in carers of people with long
      term mental health difficulties.
AB  - BACKGROUND: Expressed emotion (EE) is a global index of familial emotional
      climate, which is comprised of emotional over-involvement (EOI) and critical
      comments (CC)/hostility. Although EE is an established predictor of negative
      outcomes for both people with long-term mental health difficulties and their
      family carers, its psychological underpinnings remain relatively poorly
      understood. This paper examined associations between attachment, mentalisation
      ability and aspects of EE. METHODS: Carers of people with long-term mental health
      difficulties (n = 106) completed measures of adult attachment (the Experiences in
      Close Relationships-Short Form questionnaire), mentalisation (the Reading the
      Mind in the Eyes Test and the Emotional Self-Efficacy Scale) and EE (the Family
      Questionnaire). Data were analysed using hierarchical multiple regression.
      RESULTS: Attachment avoidance and facets of mentalisation were directly and
      uniquely positively associated with CC/hostility, with attachment avoidance and
      other-directed emotional self-efficacy (one facet of mentalisation) each
      significantly predicting CC/hostility scores after controlling for the effects of
      EOI and demographic variables. However, no associations were observed between
      EOI, attachment anxiety and mentalisation. Furthermore, no indirect effects from
      attachment to EE via mentalisation was found. CONCLUSIONS: Although it would be
      premature to propose firm clinical implications based on these findings, data
      indicate that it may be beneficial for clinicians to consider attachment and
      mentalisation in their conceptualisation of carers' criticism and hostility.
      However, further research is needed to clarify the magnitude of these
      associations and their direction of effect before firm conclusions can be drawn.

PMID- 30115041
TI  - Prompt mental health care, the Norwegian version of IAPT: clinical outcomes and
      predictors of change in a multicenter cohort study.
AB  - BACKGROUND: Prompt mental health care (PMHC) is a Norwegian initiative, inspired
      by the English 'Improving Access to Psychological Therapy' (IAPT), aimed to
      provide low-threshold access to primary care treatment for persons with symptoms
      of anxiety and depression. The objectives of the present study are to describe
      the PMHC service, to examine changes in symptoms of anxiety and depression
      following treatment and to identify predictors of change, using data from the 12
      first pilot sites. METHODS: A prospective cohort design was used. All
      participants were asked to complete questionnaires at baseline, before each
      treatment session and at the end of treatment. Effect sizes (ES) for pre-post
      changes and recovery rates were calculated based on the Patient Health
      Questionnaire and the Generalized Anxiety Disorder scale. Multiple imputation
      (MI) was used in order to handle missing data. We examined predictors through
      latent difference score models and reported the contribution of each predictor
      level in terms of ES. RESULTS: In total, N = 2512 clients received treatment at
      PMHC between October 2014 and December 2016, whereof 61% consented to
      participate. The changes from pre- to post-treatment were large for symptoms of
      both depression (ES = 1.1) and anxiety (ES = 1.0), with an MI-based reliable
      recovery rate of 58%. The reliable recovery rate comparable to IAPT based on last
      observation-carried-forward was 48%. The strongest predictors for less
      improvement were having immigrant background (ES change depression - 0.27, ES
      change anxiety - 0.26), being out of work at baseline (ES change depression -
      0.18, ES change anxiety - 0.35), taking antidepressants (ES change anxiety -
      0.36) and reporting bullying as cause of problems (ES change depression - 0.29).
      Taking sleep medication did on the other hand predict more improvement (ES change
      depression 0.23, ES change anxiety 0.45). CONCLUSIONS: Results in terms of
      clinical outcomes were promising, compared to both the IAPT pilots and other
      benchmark samples. Though all groups of clients showed substantial improvements,
      having immigrant background, being out of work, taking antidepressant medication
      and reporting bullying as cause stood out as predictors of poorer treatment
      response. Altogether, PMHC was successfully implemented in Norway. Areas for
      improvement of the service are discussed.

PMID- 30115040
TI  - The validity of Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5) as
      screening instrument with Kurdish and Arab displaced populations living in the
      Kurdistan region of Iraq.
AB  - BACKGROUND: The Posttraumatic Stress Disorder Checklist (PCL) is a valid and
      reliable self-report measure for the assessment of Posttraumatic Stress Disorder
      (PTSD). Recently the PCL was updated according to the DSM-5 criteria for PTSD. So
      far only a few studies have examined the psychometric properties of the PCL-5,
      and all of these are restricted to populations living in industrialized
      countries. The aim of this study was to determine the psychometric properties and
      diagnostic utility of the PCL-5 as a screening instrument for war-affected
      displaced Kurdish and Arab populations. The specific goal was to determine a
      contextually valid cut-off score for a probable diagnosis of PTSD. METHODS: The
      PCL-5 was translated into Arabic and two Kurdish dialects. Trained interviewers
      administered these translations as assisted self-reports to 206 adults living in
      camps for displaced people in Iraq, together with depression and war-exposure
      instruments. Two weeks later, 98 randomly chosen subjects were reassessed by
      expert clinical psychologists. In the absence of a gold-standard instrument with
      proven validity in this context, the expert interviewers applied the PCL-5 items
      in the form of a clinical interview and used a DSM-5-algorithm to determine a
      diagnosis of PTSD. Receiver operator characteristics (ROC) were performed to
      determine a valid cutoff-score. RESULTS: The internal consistency of the PCL-5
      was high (alpha = .85) and the instrument showed an adequate convergent validity.
      Using the cut-off score of 23, the PCL-5 achieved the optimal balance of
      sensitivity and specificity (area under the curve = .82, p < .001; sensitivity =
      .82, specificity = .70). CONCLUSIONS: Given that the comparison of the two
      assessments included both a re-test interval and validation by different
      interviewers, our results indicate that the PCL-5 can be recommended as an
      assessment and screening instrument for Kurdish and Arab populations.

PMID- 30115042
TI  - The use of intravenous versus subcutaneous monoclonal antibodies in the treatment
      of severe asthma: a review.
AB  - BACKGROUND: Monoclonal antibodies (mAbs) approved for use as add-on therapy in
      patients with severe asthma target the underlying pathogenesis of asthma. MAIN
      BODY: Omalizumab binds immunoglobulin E (IgE), thereby inhibiting its interaction
      with the high-affinity IgE receptor and reducing the quantity of free IgE
      available to trigger the allergic cascade. Anti-interleukin (IL)-5 mAbs
      mepolizumab, benralizumab and reslizumab block the interaction between IL-5 and
      its receptor on eosinophils, thus targeting the eosinophilic pathway in asthma.
      Most mAbs are available as intravenous (IV) or subcutaneous (SC) formulations, as
      their high molecular weight and gastric degradation preclude oral administration.
      This review compares the pharmacology, efficacy, immunogenicity, injection- and
      infusion-related adverse drug reactions of subcutaneously administered omalizumab
      and mepolizumab with the intravenously administered reslizumab. In terms of
      pharmacokinetics, IV route of administration appears to be superior to the SC
      route due to quicker absorption, greater bioavailability, shorter time to maximum
      serum concentration and similar elimination half-life. Route of administration
      does not appear to translate into striking differences in efficacy and safety of
      mAbs used for the treatment of severe asthma, as all are generally considered to
      be effective and well tolerated. Hypersensitivity and administration-related
      reactions have been described with both IV and SC mAbs. CONCLUSION: mABs are
      effective and have low immunogenicity due to their nature as humanised
      antibodies. Evidence on the use of mAbs in indications other than severe asthma
      suggest that both the SC and the IV routes of administrations have their
      respective advantages and disadvantages; but their full utility remains to be
      elucidated.

PMID- 30115043
TI  - Supermarket retailers' perspectives on healthy food retail strategies: in-depth
      interviews.
AB  - BACKGROUND: Excess calorie consumption and poor diet are major contributors to
      the obesity epidemic. Food retailers, in particular at supermarkets, are key
      shapers of the food environment which influences consumers' diets. This study
      seeks to understand the decision-making processes of supermarket retailers
      including motivators for and barriers to promoting more healthy products-and to
      catalogue elements of the complex relationships between customers, suppliers,
      and, supermarket retailers. METHODS: We recruited 20 supermarket retailers from a
      convenience sample of full service supermarkets and national supermarket chain
      headquarters serving low- and high-income consumers in urban and non-urban areas
      of New York. Individuals responsible for making in-store decisions about retail
      practices engaged in online surveys and semi-structured interviews. We employed
      thematic analysis to analyze the transcripts. RESULTS: Supermarket retailers,
      mostly representing independent stores, perceived customer demand and suppliers'
      product availability and deals as key factors influencing their in-store
      practices around product selection, placement, pricing, and promotion.
      Unexpectedly, retailers expressed a high level of autonomy when making decisions
      about food retail strategies. Overall, retailers described a willingness to
      engage in healthy food retail and a desire for greater support from healthy food
      retail initiatives. CONCLUSIONS: Understanding retailers' in-store decision
      making will allow development of targeted healthy food retail policy approaches
      and interventions, and provide important insights into how to improve the food
      environment.

PMID- 30115044
TI  - Time-use and environmental determinants of dropout from organized youth football
      and tennis.
AB  - BACKGROUND: Many adolescents drop out of organized sports. Lack of motivation and
      competing priorities are known as important reasons for dropout. However, time
      use factors as well as environmental determinants have been largely neglected in
      the current literature on dropout from youth sports. The aim of this study is to
      investigate how (changes in) time use and characteristics of the physical
      environment determine dropout from football and tennis among adolescents.
      METHODS: Data on time use and background characteristics were collected through
      online surveys in 2015 and 2016 among adolescents aged 13-21 (N = 2555),
      including both the dropped outs and those who still continued membership of their
      football or tennis clubs. Physical environmental determinants (travel distance to
      the sports club, and neighbourhood density) were measured objectively. Binary
      logistic regression analyses were carried out for football and tennis separately
      to examine the associations between time use (time spent on various activities
      and changes related to the school and job situation), and environmental factors
      on the probability of dropping out from sports. RESULTS: Time spent on sports
      outside the context of the sports club, and time spent on social or voluntary
      activities at the sports club was positively associated with continuing being
      football and tennis members. Tennis players who changed schools or participated
      in two sports at the same time had a higher probability of dropping out, whereas
      tennis players who travelled greater distances from home to the tennis club were
      less likely to drop out. CONCLUSIONS: Determinants of dropout differed between
      football and tennis. However, time use variables were important predictors of
      dropout from football as well as tennis, whereas environmental determinants
      hardly contributed to the prediction of dropout. To keep youths involved in
      organized sports, this study recommends that sports professionals should: 1)
      offer flexibility in training and competition schedules, 2) stimulate
      participation in social activities and voluntary work at the sports club, 3) pay
      special attention to their needs and preferences, and 4) encourage possibilities
      to practice and play sports outside of regular training hours, for instance at
      the sports club or at playgrounds or parks in the neighbourhood.

PMID- 30115045
TI  - Predictors of postpartum contraceptive use in rural Tigray region, northern
      Ethiopia: a multilevel analysis.
AB  - BACKGROUND: Postpartum family planning services is one of the recommended public
      health intervention aimed at reducing maternal and child morbidity and
      mortalities. However, there is a paucity studies in rural Tigray region.
      Therefore, determining the level and associated factors of contraceptive use
      among postpartum women has the potential to contribute in achieving the Ethiopian
      Health Sector Transformation Plan and to the Sustainable Development Goals on
      maternal and infant survival. METHODS: A community-based cross-sectional study
      was done among 1109 postpartum women from March 29, 2017 to April 29, 2017. Face 
      to-face interview was used for data collection. The collected data were entered
      and cleaned using EPI - INFO version 7statistical software and later exported to
      and analyzed using STATA version 12. Mixed-effects multilevel logistic regression
      analysis was used to identify the individual and community-level factors
      associated with contraception adoption. A two side p-value< 0.05 was considered
      to be statistically significant. RESULTS: The level of contraceptive use was
      38.3%. Individual-level variables such as women belong to fourth (AOR = 1.2; 95%
      CI: 1.1-3.2) and fifth (AOR = 1.5; 95% CI: 1.3-2.5) wealth quintiles were
      identified as key predictors of contraception use. In addition, partner secondary
      (AOR = 2.3; 95% CI: 1.8-3.5) and diploma (AOR = 1.2; 95% CI, 1.1-2.6) educational
      level and postnatal care (AOR = 2.0; 95% CI: 1.9, 4.3) were also significantly
      affected contraception use. Community-level variables such as high community
      level antenatal care services use (AOR = 2.1; 95% CI: 1.9-4.2) and proximity of
      women to health facility (AOR = 3.0; 95% CI: 2.7-4.6) were also determinants of
      contraception uptake. CONCLUSIONS: The status of contraceptive use in rural
      Tigray region was found to be low. It was found that both individual and
      community-level variables showed a marked determinant on postpartum contraception
      use. This study suggested that in order to increase contraceptive use the
      government should focus on increasing postnatal care, antenatal care services use
      and reduction of poverty level are important avenues for intervention.

PMID- 30115046
TI  - Persistent synovial inflammation plays important roles in persistent pain
      development in the rat knee before cartilage degradation reaches the subchondral
      bone.
AB  - BACKGROUND: The major complaint of knee osteoarthritis (OA) is persistent pain.
      Unlike acute inflammatory pain, persistent pain is usually difficult to manage
      since its pathology is not fully understood. To elucidate the underlying
      mechanisms of persistent pain, we established 2 different inflammation-induced
      arthritis models by injecting monoiodo-acetic acid (MIA) into the joint cavity
      and performed integrated analyses of the structural changes in the synovial
      tissue and articular cartilage, sensory neuron rearrangement, and pain avoidance
      behavior in a rat arthritis model. METHODS: Male Wistar rats received intra
      articular injections of MIA (0.2 mg/30 MUL, low-dose group; 1 mg/30 MUL, high
      dose group) in the right knee and phosphate buffered saline (PBS; 30 MUL, control
      group) in the left knee. Fluorogold (FG), a retrograde neural tracer, was used to
      label the nerve fibers for the identification of sensory neurons that dominate
      the joints in the dorsal root ganglion (DRG). Both knees were subjected to the
      intra-articular injection of 2% FG in PBS (5 MUL) under anesthesia 5-7 days prior
      to sacrifice. We performed pain avoidance behavior tests (incapacitance and von
      Frey tests) at 0, 1, 3, 5, 7, 14, 21, and 28 days. At 5, 14, and 28 days, the
      rats were sacrificed and the knee joint and DRG were excised for histological
      assessment. The knee joints were stained with hematoxylin and eosin, safranin O,
      and calcitonin gene-related peptide (CGRP). The DRG were immunostained with CGRP.
      RESULTS: A transient inflammatory response followed by mild articular cartilage
      degeneration was observed in the low-dose MIA model versus persistent
      inflammation with structural changes in the synovial tissue (fibrosis) in the
      high-dose model. In the high-dose model, full-thickness cartilage degeneration
      was observed within 2 weeks post-MIA injection. The pain avoidance behavior tests
      indicated that persistent synovial inflammation and structural changes of the
      infrapatellar fat pad may play important roles in persistent knee joint pain
      before the articular cartilage degeneration reaches the subchondral bone.
      CONCLUSIONS: Transient inflammation without structural changes of the synovial
      tissues did not induce persistent pain in the rat knee joint before degradation
      of the articular cartilage reached the subchondral bone plate.

PMID- 30115047
TI  - Development of a core outcome set for therapeutic clinical trials enrolling dogs
      with atopic dermatitis (COSCAD'18).
AB  - BACKGROUND: For decades, the efficacy of interventions in clinical trials
      enrolling dogs with atopic dermatitis (AD) relied on heterogeneous evaluations of
      skin lesions and pruritus using unvalidated tools. Although some instruments for
      clinical signs were validated later, there was little impact on standardizing
      outcome measures resulting in difficulties in comparing treatment efficacy
      between trials and impeding meta-analyses. RESULTS: Participants in the Outcome
      Measures subcommittee of the International Committee of Allergic Diseases of
      Animals (ICADA) collaborated for two years to develop a core outcome set (COS)
      for canine AD, the COSCAD. This project involved several steps, constantly-re
      assessed during online exchanges, to define the scope of this COS, to identify
      the relevant stakeholders, the domains to be evaluated, the instruments available
      for measuring agreed-upon domains and how to express outcome measures. This
      COSCAD'18 was designed principally for therapeutic-but not preventive or
      proactive-clinical trials enrolling dogs with chronic, nonseasonal (perennial),
      moderate-to-severe AD. Selected domains were skin lesions, pruritus
      manifestations and perception of treatment efficacy. Instruments to evaluate
      these domains were the CADESI4 or CADLI, the 10-point pruritus visual analog
      scale (PVAS10) and the Owner Global Assessment of Treatment Efficacy (OGATE),
      respectively. The COSCAD'18 has three outcome measures: the percentages of dogs
      with veterinarian-assessed skin lesions or owner-rated pruritus manifestation
      scores in the range of normal dogs or those with mild AD; the third is a good-to
      excellent global assessment by the pet owners of their perception of treatment
      efficacy. Importantly, this COSCAD'18 is not meant to represent the sole-or
      primary-outcome measures evaluated in a trial; authors are always free to add any
      others, which they deem will best assess the efficacy of tested interventions.
      Benchmarks to define a threshold for treatment success were not set, as what
      constitutes a clinically-relevant therapeutic efficacy is expected to vary
      greatly depending interventions. CONCLUSIONS: This COSCAD'18 should help
      veterinarians and owners compare the benefits of treatments in future trials.
      This COS should also facilitate the combination of trial results in future
      systematic reviews, thereby producing more reliable summary estimates of
      treatment effects and enhancing evidence-based veterinary dermatology.

PMID- 30115048
TI  - Uptake of the NICE osteoarthritis guidelines in primary care: a survey of older
      adults with joint pain.
AB  - BACKGROUND: Osteoarthritis (OA) is a leading cause of pain and disability. NICE
      OA guidelines (2008) recommend that patients with OA should be offered core
      treatments in primary care. Assessments of OA management have identified a need
      to improve primary care of people with OA, as recorded use of interventions
      concordant with the NICE guidelines is suboptimal in primary care. The aim of
      this study was to i) describe the patient-reported uptake of non-pharmacological
      and pharmacological treatments recommended in the NICE OA guidelines in older
      adults with a self-reported consultation for joint pain and ii) determine whether
      patient characteristics or OA diagnosis impact uptake. METHODS: A cross-sectional
      survey mailed to adults aged >=45 years (n = 28,443) from eight general practices
      in the UK as part of the MOSAICS study. Respondents who reported the presence of
      joint pain, a consultation in the previous 12 months for joint pain, and gave
      consent to medical record review formed the sample for this study. RESULTS: Four
      thousand fifty-nine respondents were included in the analysis (mean age 65.6
      years (SD 11.2), 2300 (56.7%) females). 502 (12.4%) received an OA diagnosis in
      the previous 12 months. More participants reported using pharmacological
      treatments (e.g. paracetamol (31.3%), opioids (40.4%)) than non-pharmacological
      treatments (e.g. exercise (3.8%)). Those with an OA diagnosis were more likely to
      use written information (OR 1.57; 95% CI 1.26,1.96), paracetamol (OR 1.30; 95% CI
      1.05,1.62) and topical NSAIDs (OR 1.30; 95% CI 1.04,1.62) than those with a joint
      pain code. People aged >=75 years were less likely to use written information (OR
      0.56; 95% CI 0.40,0.79) and exercise (OR 0.37; 95% CI 0.25,0.55) and more likely
      to use paracetamol (OR 1.91; 95% CI 1.38,2.65) than those aged < 75 years.
      CONCLUSION: The cross-sectional population survey was conducted to examine the
      uptake of the treatments that are recommended in the NICE OA guidelines in older
      adults with a self-reported consultation for joint pain and to determine whether
      patient characteristics or OA diagnosis impact uptake. Non-pharmacological
      treatment was suboptimal compared to pharmacological treatment. Implementation of
      NICE guidelines needs to examine why non-pharmacological treatments, such as
      exercise, remain under-used especially among older people.

PMID- 30115050
TI  - Barriers and facilitators to the integration of depression services in primary
      care in Vietnam: a mixed methods study.
AB  - BACKGROUND: Although the prevalence of depression in Vietnam is on par with
      global rates, services for depression are limited. The government of Vietnam has
      prioritized enhancing depression care through primary healthcare (PHC) and
      efforts are currently underway to test and scale-up psychosocial interventions
      throughout the country. With these initiatives in progress, it is important to
      understand implementation factors that might influence the successful integration
      of depression services into PHC. As the implementers of these new interventions,
      primary care providers (PHPs) are well placed to provide important insight into
      implementation factors affecting the integration of depression services into PHC.
      This mixed-methods study examines factors at the individual, organizational and
      structural levels that may act as barriers and facilitators to the integration of
      depression services into PHC in Vietnam from the perspective of PHPs. METHODS:
      Data collection took place in Hanoi, Vietnam in 2014. We conducted semi
      structured interviews with PHPs (n = 30) at commune health centres and outpatient
      clinics in one rural and one urban district of Hanoi. Theoretical thematic
      analysis was used to analyse interview data. We administered an online survey to
      PHPs at n = 150 randomly selected communes across Hanoi. N = 226 PHPs responded
      to the survey. We used descriptive statistics to describe the study variables
      acting as barriers and facilitators and used a chi-square test of independence to
      indicate statistically significant (p < .05) associations between study variables
      and the profession, location and gender of PHPs. RESULTS: Individual-level
      barriers include low level of knowledge and familiarity with depression among
      PHPs. Organizational barriers include low resource availability in PHC and low
      managerial discretion. Barriers at the structural level include limited mental
      health training among all PHPs and the existing programmatic structure of PHC in
      Vietnam, which sets mental health apart from general services. Facilitators at
      the individual level include positive attitudes among PHPs towards people with
      depression and interest in undergoing enhanced training in depression service
      delivery. CONCLUSIONS: While facilitating factors at the individual level are
      encouraging, considerable barriers at the structural level must be addressed to
      ensure the successful integration of depression services into PHC in Vietnam.

PMID- 30115049
TI  - Oral administration of inactivated porcine epidemic diarrhea virus activate DCs
      in porcine Peyer's patches.
AB  - BACKGROUND: Peyer's patches (PPs) can be considered as the immune site of the
      intestine. Within PPs, Dendritic cells (DCs) can uptake antigens from the gut
      lumen by extending dendrites into epithelium, and process it and then present to
      lymphocytes, which effectively antigen produces an immune response. Porcine
      epidemic diarrhea virus (PEDV) is the causative agent of porcine epidemic
      diarrhea (PED), an acute and highly contagious enteric viral disease. The
      interaction between inactivated porcine epidemic diarrhea virus and porcine
      monocyte-derived dendritic cells (Mo-DCs) has been reported. However, little is
      known about the interaction between inactivated PEDV and DCs in porcine PPs.
      RESULTS: In this study, for the first time we investigated the role of DCs in
      porcine PPs after oral administration inactivated PEDV. Firstly, a method to
      isolate DCs from porcine PPs was established, in which the purity of SWC3a+/MHC
      II+ DCs was more than 90%. Our findings clearly indicate that DCs in porcine PPs
      after oral administration of inactivated PEDV not only stimulated the
      proliferation of allogeneic lymphocytes, but also secreted cytokines (IL-1, IL
      4). Furthermore, the number of DCs and IgA+ cells in porcine intestinal mucosal
      significantly increased and the levels of anti-PEDV specific IgG antibody in the
      serum and SIgA antibody in the feces increased after oral administration
      inactivated PEDV. CONCLUSIONS: Our findings indicate that oral administration of
      inactivated PEDV activate DCs in porcine Peyer's patches and inactivated PEDV may
      be a useful and safe vaccine to trigger adaptive immunity.

PMID- 30115051
TI  - A pre and post intervention study to reduce unnecessary urinary catheter use on
      general internal medicine wards of a large academic health science center.
AB  - BACKGROUND: Urinary catheters are a common medical intervention, yet they can
      also be associated with harmful adverse events such as infection, urinary tract
      trauma, delirium and patient discomfort. The purpose of this study was to
      describe the use of the SafetyLEAP program to drive improvement efforts, and
      specifically to reduce the use of urinary catheters on general internal medicine
      wards. METHODS: A pre and post intervention study using the SafetyLEAP program
      was performed with urinary catheter prevalence as the primary outcome on two
      general internal medicine wards in a large academic health sciences center.
      RESULTS: A total of n = 534 patients (n = 283 from ward #1; and n = 252 from ward
      #2) were included in the initial audit and feedback portion of the study and 1601
      patients (n = 824 pre-intervention and n = 777 post-intervention were included in
      the planned quality improvement portion of the study). A total of 379 patients
      during the quality improvement intervention had a urinary catheter. Overall, the
      adherence to the SafetyLEAP program was 97.4% on both general internal medicine
      wards. The daily catheter point prevalence decreased from 22 to 13%. After the
      implementation of the program, the urinary catheter utilization ratio (defined as
      urinary catheter days/patient days) declined from 0.14 to 0.12. Catheter
      associated urinary tract infections (CAUTI) were unchanged. CONCLUSION: The
      SafetyLEAP program can help provide a systematic approach to the detection, and
      reduction of safety incidents. Future studies should aim at refining and
      implementing this intervention broadly.

PMID- 30115052
TI  - Nutrient foramen location on the laminae provides a landmark for pedicle screw
      entry: a cadaveric study.
AB  - BACKGROUND: Nutrient foramina are often encountered around the entry point of
      pedicle screws. Further, while probing the pedicle for pedicle screw insertion
      around the nutrient foramen, bleeding from the probe insertion hole is often
      observed. The purpose of this study was to investigate the frequency of
      occurrence of nutrient foramina, the association between the nutrient foramen and
      pedicle, and the safety and accuracy of cervical and thoracic pedicle screw
      placement using the nutrient foramen as the entry point. METHODS: We identified
      the location of the nutrient foramina for the dorsal branches of the segmental
      artery and their anatomical association to the pedicles and bony landmarks in the
      vertebrae for C3-T12 in seven cadavers. We also determined the frequency with
      which the nutrient foramina were present in 119 cadaveric vertebrae. We
      identified the pedicle location, base of the superior articular facet, and
      lateral border of laminae with respect to the nutrient foramen. RESULTS: The
      overall presence of the nutrient foramina was 63% (150/238) in the specimens,
      with 60% (42/70) and 64% (108/168) identifiable in the cervical and thoracic
      vertebrae, respectively. In the cervical vertebrae, the nutrient foramen was
      located on the outer wall of the pedicle and was positioned between the cephalad
      and caudal walls. In the thoracic spine, 98% (106/108) nutrient foramina were
      located inside the pedicle walls. CONCLUSIONS: Our study findings confirm that
      the location of the nutrient foramen can be used for identifying the entry point
      for pedicle screws. In the cervical vertebrae, the nutrient foramina are located
      lateral to pedicle but within the cranial and caudal margins. In the thoracic
      vertebrae, the nutrient foramina are located in the medial and caudal regions of
      the pedicle. Thus, to decrease the risk of overshoot, the entry point for
      thoracic pedicle screws should be positioned a few millimeters cephalad and
      lateral to the nutrient foramen.

PMID- 30115053
TI  - Annular closure device for disc herniation: meta-analysis of clinical outcome and
      complications.
AB  - BACKGROUND: Lumbar intervertebral disc herniation is a common cause of lower back
      and leg pain, with surgical intervention (e.g. discectomy to remove the herniated
      disc) recommended after an appropriate period of conservative management, however
      the existing or increased breach of the annulus fibrosus persists with the
      potential of reherniation. Several prosthesis and techniques to reduce re
      herniation have been proposed including implantation of an annular closure device
      (ACD) - BarricaidTM and an annular tissue repair system (AR) - Anulex-XcloseTM.
      The aim of this meta-analysis is to assist surgeons determine a potential
      approach to reduce incidences of recurrent lumbar disc herniation and assess the
      current devices regarding their outcomes and complications. METHODS: Four
      electronic full-text databases were systematically searched through September
      2017. Data including outcomes of annular closure device/annular repair were
      extracted. All results were pooled utilising meta-analysis with weighted mean
      difference and odds ratio as summary statistics. RESULTS: Four studies met
      inclusion criteria. Three studies reported the use of Barricaid (ACD) while one
      study reported the use of Anulex (AR). A total of 24 symptomatic reherniation
      were reported among 811 discectomies with ACD/AR as compared to 51 out of 645 in
      the control group (OR: 0.34; 95% CI: 0.20,0.56; I2 = 0%; P < 0.0001). Durotomies
      were lower among the ACD/AR patients with only 3 reported cases compared to 7 in
      the control group (OR: 0.54; 95% CI: 0.13, 2.23; I2 = 11%; P = 0.39). Similar
      outcomes for post-operative Oswestry Disability Index and visual analogue scale
      were obtained when both groups were compared. CONCLUSION: Early results showed
      the use of Barricaid and Anulex devices are beneficial for short term outcomes
      demonstrating reduction in symptomatic disc reherniation with low post-operative
      complication rates. Long-term studies are required to further investigate the
      efficacy of such devices.

PMID- 30115054
TI  - A program evaluation of an in-school daily physical activity initiative for
      children and youth.
AB  - BACKGROUND: The school system is one setting in which children's physical
      activity levels may be increased through daily physical activity (DPA) policies
      and initiatives. Adherence to DPA policies is typically poor and results are
      limited in regard to the associated benefits for participating children.
      Therefore, the purpose of this study was to evaluate a range of psychosocial
      outcomes following a community-led, in-school DPA initiative for 9-14 year old
      children and youth. METHODS: This program evaluation examined the impact of a DPA
      program consisting of 20 min of teacher-led DPA for 20 consecutive weeks. Student
      outcomes were measured using a questionnaire administered at three time points:
      baseline, mid-intervention, and post-intervention. A teacher questionnaire
      regarding program adherence and student behaviour was completed at post
      intervention. Mixed effects models were used to test for intervention effects,
      with random intercepts for students, classes, and schools, as well as fixed
      effects for age and sex. Due to the large number of outcomes measured, we first
      conducted an omnibus test of the intervention effect followed by three
      exploratory analyses examining each outcome separately, associations between
      outcomes and program adherence, and results from the teacher survey. RESULTS:
      Thirty classes (N = 19 experimental) from 7 schools participated in the study,
      with a total of 362 children (n = 265 experimental). There was no significant
      overall effect of the intervention (z = 0.89, p = 0.38) and the exploratory
      analyses demonstrated significant differences only for self-esteem and subjective
      happiness, with the control group slightly increasing relative to the
      experimental group. Teacher-reported adherence to the program was poor with only
      21% of teachers adhering to the program. There was no association between overall
      adherence and student reported outcomes; however, positive correlations were
      present between adherence and teacher-reported student behaviour. CONCLUSIONS:
      The DPA program evaluated here did not improve the psychosocial well-being of
      elementary school-aged children more than usual practices. However, adherence to
      the program was poor and it did not have a negative effect on the students.
      Future work is needed on how best to support DPA implementation in the context of
      the school day and how student well-being may be positively impacted through
      school-based physical activity. TRIAL REGISTRATION: Program Evaluation of an in
      school Daily Physical Activity Initiative NCT03618927 , August 6, 2018.
      Retrospectively registered.

PMID- 30115055
TI  - Use of The Global Alliance for Musculoskeletal Health survey module for
      estimating the population prevalence of musculoskeletal pain: findings from the
      Solomon Islands.
AB  - BACKGROUND: Musculoskeletal (MSK) conditions are common and the biggest global
      cause of physical disability. The objective of the current study was to estimate
      the population prevalence of MSK-related pain using a standardized global MSK
      survey module for the first time. METHODS: A MSK survey module was constructed by
      the Global Alliance for Musculoskeletal Health Surveillance Taskforce and the
      Global Burden of Disease MSK Expert Group. The MSK module was included in the
      2015 Solomon Islands Demographic and Health Survey. The sampling design was a two
      stage stratified, nationally representative sample of households. RESULTS: A
      total of 9214 participants aged 15-49 years were included in the analysis. The
      age-standardized four-week prevalence of activity-limiting low back pain, neck
      pain, and hip and/or knee pain was 16.8, 8.9, and 10.8%, respectively. Prevalence
      tended to increase with age, and be higher in those with lower levels of
      education. CONCLUSIONS: Prevalence of activity-limited pain was high in all
      measured MSK sites. This indicates an important public health issue for the
      Solomon Islands that needs to be addressed. Efforts should be underpinned by
      integration with strategies for other non-communicable diseases, aging,
      disability, and rehabilitation, and with other sectors such as social services,
      education, industry, and agriculture. Primary prevention strategies and
      strategies aimed at self-management are likely to have the greatest and most cost
      effective impact.

PMID- 30115056
TI  - Social network and HIV risk behaviors in female sex workers: a systematic review.
AB  - BACKGROUND: Social network characteristics have an important role in
      understanding HIV transmission among female sex workers. The purpose of this
      systematic review was to summarize and critically appraise the existing studies
      on the social network characteristics and HIV risk behaviors among female sex
      workers. METHOD: A systematic review was performed using predefined eligibility
      criteria through searching electronic databases. Two independent reviewers
      assessed the methodological quality of studies. RESULTS: Nineteen papers met the
      eligible review criteria. The synthesized evidence suggests that characteristics
      of social networks, especially functional characteristics such as social support
      and social capital, are important constructs for understanding the HIV risk
      behaviors. CONCLUSIONS: The findings of the present review enhance our
      understanding of the role of social network characteristics in HIV risk behaviors
      among female sex workers. However, the findings also highlighted a dearth of
      knowledge about the association of structural characteristics of social networks
      with HIV risk behaviors among female sex workers.

PMID- 30115058
TI  - Distinct metabolic profile according to the shape of the oral glucose tolerance
      test curve is related to whole glucose excursion: a cross-sectional study.
AB  - BACKGROUND: The shapes of the plasma glucose concentration curve during the oral
      glucose tolerance test are related to different metabolic risk profiles and
      future risk of type 2 DM. We sought to further analyze the relationship between
      the specific shapes and hyperglycemic states, the metabolic syndrome and hormones
      involved in carbohydrate and lipid metabolism, and to isolate the effect of the
      shape by adjusting for the area under the glucose curve. METHODS: One hundred
      twenty one adult participants underwent a 2-h oral glucose tolerance test and
      were assigned to either the monophasic (n = 97) or the biphasic (n = 24) group
      based upon the rise and fall of their plasma glucose concentration. We evaluated
      anthropometric measures, blood pressure, lipid profile, high-sensitivity C
      reactive protein, glycated hemoglobin, insulin sensitivity, beta-cell function, C
      peptide, glucagon, adiponectin and pancreatic polypeptide. RESULTS: Subjects with
      monophasic curves had higher fasting and 2-h plasma glucose levels, while
      presenting lower insulin sensitivity, beta-cell function, HDL cholesterol,
      adiponectin and pancreatic polypeptide levels. Prediabetes and metabolic syndrome
      had a higher prevalence in this group. Glycated hemoglobin, total cholesterol,
      triglycerides, high-sensitivity C-reactive protein and glucagon were not
      significantly different between groups. After adjusting for the area under the
      glucose curve, only the differences in the 1-h and 2-h plasma glucose
      concentrations and HDL cholesterol levels between the monophasic and biphasic
      groups remained statistically significant. CONCLUSIONS: Rates and intensity of
      metabolic dysfunction are higher in subjects with monophasic curves, who have
      lower insulin sensitivity and beta-cell function and a higher prevalence of
      prediabetes and metabolic syndrome. These differences, however, seem to be
      dependent on the area under the glucose curve.

PMID- 30115057
TI  - Total hip arthroplasty following failure of tantalum rod implantation for
      osteonecrosis of the femoral head with 5- to 10-year follow-up.
AB  - BACKGROUND: Total hip arthroplasty (THA) with failure of tantalum rod implant for
      osteonecrosis of the femoral head (ONFH) will be the only choice for patients.
      However,it remains unknown whether tantalum rod implantation has an adverse
      effect on the survival time of implants following conversion to THA. The aim of
      this study was to retrospectively evaluate the clinical and radiographic outcomes
      of conversion to THA in patients who were previously treated with implantation of
      a tantalum rod. METHODS: This study included 31 patients (39 hips), who underwent
      conversion to THA due to failure of core decompression with an implanted tantalum
      rod. Among these 31 patients, 26 patients were male and five patients were
      female. The mean age of these patients was 49.3 years old (range: 36-64 years
      old). The control group included 33 patients (40 hips), who underwent total hip
      replacement without tantalum rod implantation. The hip Harris score, implant
      wear, osteolysis, radiolucencies and surgical complications were recorded during
      the follow-up. The distribution of tantalum debris in the proximal, middle and
      distal periprosthetic femoral regions, radiolucent lines and osteolysis were
      analyzed on post-operative radiographs. RESULTS: There were no significant
      differences in Harris score, liner wear and complications between the two groups
      (P > 0.05). Osteolysis and radiolucent lines more likely occurred in patients
      with tantalum debris distributed in three regions than in one or two regions (P <
      0.05). CONCLUSIONS: The mid-term clinical outcome of patients who underwent THA
      with tantalum rod implantation was not different from those without a tantalum
      rod, suggesting that tantalum debris did not increase the liner wear rate.
      However, the distribution of periprosthetic tantalum debris in the proximal,
      middle and distal femoral regions may increase the risk of femoral osteolysis and
      radiolucent lines.

PMID- 30115060
TI  - Neuralgia due to iliohypogastric nerve injury after inguinal hernioplasty: a case
      report.
AB  - BACKGROUND: Neuralgia due to iliohypogastric nerve entrapment from sutures and
      mesh after inguinal hernioplasty is a rare entity in clinic. Its' awareness and
      management remain a clinical challenge. CASE PRESENTATION: We report a case of 54
      year-old male who presented with post-operative pain after 1 month and sensory
      disturbances of the right lower limb. He underwent partial neurectomy and during
      the surgery it was found that there was injury to iliohypogastric nerve due to
      entrapment from sutures and mesh. CONCLUSION: We hope to strengthen awareness
      about the importance of the identification of iliohypogastric nerve during
      inguinal hernioplasty.

PMID- 30115059
TI  - The epidemiology of MRI detected shoulder injuries in athletes participating in
      the Rio de Janeiro 2016 Summer Olympics.
AB  - BACKGROUND: To use Magnetic Resonance Imaging (MRI) to characterize the severity,
      location, prevalence, and demographics of shoulder injuries in athletes at the
      Rio de Janeiro 2016 Summer Olympic Games. METHODS: This was a retrospective
      analysis of all routine shoulder MRIs obtained from the Olympic Village
      Polyclinic during the Rio 2016 Summer Olympics. Imaging was performed on 1.5 T
      and 3 T MRI, and interpretation was centrally performed by a board-certified
      musculoskeletal radiologist. Images were assessed for tendon, muscle, bone,
      bursal, joint capsule, labral, and chondral abnormality. RESULTS: A total of
      11,274 athletes participated in the Games, of which 55 (5%) were referred for a
      routine shoulder MRI. Fifty-three (96%) had at least two abnormal findings. Seven
      (13%) had evidence of an acute or chronic anterior shoulder dislocation. Forty
      nine (89%) had a rotator cuff partial tear and / or tendinosis. Subacromial /
      subdeltoid bursitis was present in 29 (40%). Thirty (55%) had a tear of the
      superior labrum anterior posterior (SLAP). CONCLUSION: Our study demonstrated a
      high prevalence of both acute and chronic shoulder injuries in the Olympic
      athletes receiving shoulder MRI. The high rates of bursal, rotator cuff, and
      labral pathology found in these patients implies that some degree of glenohumeral
      instability and impingement is occurring, likely due to fatigue and overuse of
      the dynamic stabilizers. Future studies are needed to better evaluate sport
      specific trends of injury.

PMID- 30115061
TI  - Balloon pulmonary angioplasty - efficient therapy of chronic thromboembolic
      pulmonary hypertension in the patient with advanced sarcoidosis - a case report.
AB  - BACKGROUND: Approximately a quarter of patients with advanced sarcoidosis develop
      pulmonary hypertension (PH), which affects their prognosis. We report unusual
      case of confirmed chronic thromboembolic pulmonary hypertension (CTEPH) in a
      patient with stage IV sarcoidosis successfully treated with balloon pulmonary
      angioplasty (BPA). CASE PRESENTATION: A 65 years old male with a history of
      colitis ulcerosa, and pulmonary sarcoidosis diagnosed in 10 years before, on long
      term oral steroids, with a history of deep vein thrombosis and acute pulmonary
      embolism chronically anticoagulated was referred to our center due to severe
      dyspnea. On admission he presented WHO functional class IV, mean pulmonary artery
      pressure (mPAP) in right heart catheterization (RHC) was elevated to 54 mmHg.
      Diagnosis of CTEPH was definitely confirmed with typical V/Q scan, and with
      selective pulmonary angiography (PAG) completes by intravascular imagining
      (intravascular ultrasound, optical coherent tomography). The patient was deemed
      inoperable by CTEPH team and two sessions of BPA with multimodal approach
      resulted in significant clinical and haemodynamical improvement to WHO class II
      and mPAP decrease to 27 mmHg. CONCLUSIONS: Balloon pulmonary angioplasty, rapidly
      developing method of treatment of inoperable CTEPH patients, is also extremely
      useful therapeutic tool in complex PH patients.

PMID- 30115062
TI  - Risk factors and outcomes in asymmetrical femoral component size for posterior
      referencing bilateral total knee arthroplasty: a matched pair analysis.
AB  - BACKGROUND: Theoretically, potential errors in femoral component (FC) sizing can
      affect postoperative functional outcomes after total knee arthroplasty (TKA),
      including range of motion (ROM), anterior knee pain, and flexion stability.
      Incidences of asymmetrical femoral components (AFC) in bilateral TKA have been
      reported; however; there is a lack of data on exactly why AFC size selection may
      differ in patients who have had posterior referencing system bilateral TKA.
      Therefore, this study was conducted to determine risk factors of AFC size
      selection in patients specifically undergoing posterior referencing bilateral TKA
      and to compare clinical outcomes between those with AFC or symmetrical femoral
      component (SFC) sizes. METHODS: We conducted a retrospective matched-pair study
      comparing thirty-four patients who had undergone simultaneous and staged
      bilateral TKA using AFC size (Group I) and thirty-five patients with SFC size
      (Group II). Patients were matched according to gender, body mass index,
      prosthesis type, and operative technique. Preoperative radiographic morphology of
      both distal femurs including anteroposterior/mediolateral diameters, anterior
      posterior femoral offset, and postoperative radiographic data of FC comprising
      flexion and valgus angle were recorded. The postoperative functional outcomes
      including ROM, anterior knee pain, knee society score, and functional score at 6
      weeks, 3, 6, 12 and 24 months were compared. RESULTS: There were no differences
      in morphology between left and right distal femurs from preoperative radiographic
      data in both groups. The postoperative radiograph showed a significantly greater
      FC flexion angle difference in Group I vs. Group II (2.18 degrees  +/- 1.29
      degrees  and 1.36 degrees  +/- 1.08 degrees  P = 0.007), while the other
      parameters were the same. The postoperative clinical outcomes displayed no
      distinction between groups. CONCLUSION: The factor primarily associated with AFC
      size selection in bilateral TKAs is the difference in FC flexion angle but not
      the morphological diversity between sides. The postoperative functional outcomes
      were not inferior in AFC patients in comparison with SFC patients.

PMID- 30115063
TI  - The impact of complications on a programme of enhanced recovery in colorectal
      surgery.
AB  - BACKGROUND: The advantages of Enhanced Recovery (ER) programmes are well known,
      in terms of improved overall experience of the patients, which associates with
      low morbidity and reduced length of stay. As a result, the pattern of morbidity
      is changing and some patients may develop complications after discharge. Aim of
      this work was to evaluate the impact of morbidity and related outcomes such as
      unplanned readmission and reoperation rate on an ER programme in colorectal
      surgery. METHODS: Prospectively collected clinical data of patients who underwent
      colorectal resection have been retrospectively analysed. Endpoints were: 90-day
      mortality and morbidity, length of hospital stay (LOS) and rate of unplanned
      readmissions and reoperations. RESULTS: Mortality and morbidity did not change in
      the analysed period, but LOS reduced significantly. Main determinant of
      postoperative LOS was the type of surgical approach, laparoscopy being associated
      with earlier discharge. LOS was longer in patients who developed complications.
      Morbidity and reoperation rate were significantly higher in patients discharged
      after day 4. Majority of complications happened in patients who were still in the
      hospital. However, the few patients who developed complications after discharge
      did not have a worse outcome if compared to those who had complications in
      hospital. CONCLUSIONS: ER protocols must become integral part of the
      perioperative management of colorectal patients. ER and laparoscopy have a
      synergic effect to improve the postoperative recovery and reduce morbidity. Early
      discharge of patients does not affect the outcome of postoperative complications.

PMID- 30115064
TI  - Development and convergent validity of new self-administered questionnaires of
      active transportation in three African countries: Kenya, Mozambique and Nigeria.
AB  - BACKGROUND: There is currently a rapid physical activity transition taking place
      in developing countries that includes a decrease in active transportation.
      Building on findings from an earlier systematic review, this paper describes the
      development and convergent validity of self-administered child and parent
      questionnaires assessing active transportation of children in three African
      countries: Kenya, Mozambique and Nigeria. METHODS: A pilot study was conducted to
      examine the convergent validity of the developed questionnaires by comparing
      responses between children and their parents (N = 121; n = 43 for Mozambique, n =
      24 for Kenya and n = 54 for Nigeria). After modification, the questionnaires were
      then administered to a larger convenient sample of both children and parents from
      Kenya (n = 1123), Mozambique (n = 1097) and Nigeria (n = 831) which defined the
      main study. The questionnaires assessed active transportation to/from 8
      categories of destinations including school, friends' and relatives' home/houses,
      parks and playgrounds among others. Twenty items were used to assess child - and
      parent-perceived barriers to active transportation, and the parent questionnaire
      inquired about parent education and availability of cars, motorcycles, and
      bicycles. Spearman's rho was used to compare children's mode of travel in the
      pilot study while the prevalence-adjusted bias-adjusted kappa (PABAK) coefficient
      was used to compare convergent validity between children's and parents responses
      on active transportation in the main study. RESULTS: Findings of the main study
      show that convergent validity for active transportation to and from each
      destination in the combined sample ranged from 0.472 (from school) to 0.998 (to
      other places). Convergent validity for challenges/barriers to active
      transportation to school ranged from fair (0.30 - The route does not have good
      lighting) to substantial (0.77 - My child has a disability). It varied between
      countries from fair (n = 11-items) to moderate (n = 9-items) agreement in Kenya
      and from poor (n = 2-items) to fair (n = 16-items) agreement in Nigeria. Data
      from Mozambique was however missing and therefore could be included. CONCLUSIONS:
      The questionnaires provided valid information on the number of trips to/from
      various destinations and show acceptable and modest convergent validity for
      measuring barriers to active transport in a sample of children from three African
      countries. These questionnaires may be suitable for future research on active
      transport among school children in Sub-Saharan African countries.

PMID- 30115067
TI  - Efficacy of polymyxin B hemoperfusion in and beyond septic shock: is an
      "endotoxin severity score" needed?

PMID- 30115065
TI  - Simultaneously characterizing the comparative economics of routine female
      adolescent nonavalent human papillomavirus (HPV) vaccination and assortativity of
      sexual mixing in Hong Kong Chinese: a modeling analysis.
AB  - BACKGROUND: Although routine vaccination of females before sexual debut against
      human papillomavirus (HPV) has been found to be cost-effective around the world,
      its cost-benefit has rarely been examined. We evaluate both the cost
      effectiveness and cost-benefit of routine female adolescent nonavalent HPV
      vaccination in Hong Kong to guide its policy, and by extension that of mainland
      China, on HPV vaccination. One major obstacle is the lack of data on
      assortativity of sexual mixing. Such difficulty could be overcome by inferring
      sexual mixing parameters from HPV epidemiologic data. METHODS: We use an age
      structured transmission model coupled with stochastic individual-based
      simulations to estimate the health and economic impact of routine nonavalent HPV
      vaccination for girls at age 12 on cervical cancer burden and consider vaccine
      uptake at 25%, 50%, and 75% with at least 20 years of vaccine protection.
      Bayesian inference was employed to parameterize the model using local data on HPV
      prevalence and cervical cancer incidence. We use the human capital approach in
      the cost-benefit analysis (CBA) and GDP per capita as the indicative willingness
      to-pay threshold in the cost-effectiveness analysis (CEA). Finally, we estimate
      the threshold vaccine cost (TVC), which is the maximum cost for fully vaccinating
      one girl at which routine female adolescent nonavalent HPV vaccination is cost
      beneficial or cost-effective. RESULTS: As vaccine uptake increased, TVC decreased
      (i.e., economically more stringent) in the CBA but increased in the CEA. When
      vaccine uptake was 75% and the vaccine provided only 20 years of protection, the
      TVC was US$444 ($373-506) and $689 ($646-734) in the CBA and CEA, respectively,
      increasing by approximately 2-4% if vaccine protection was assumed lifelong. TVC
      is likely to be far higher when non-cervical diseases are included. The inferred
      sexual mixing parameters suggest that sexual mixing in Hong Kong is highly
      assortative by both age and sexual activity level. CONCLUSIONS: Routine HPV
      vaccination of 12-year-old females is highly likely to be cost-beneficial and
      cost-effective in Hong Kong. Inference of sexual mixing parameters from
      epidemiologic data of prevalent sexually transmitted diseases (i.e., HPV,
      chlamydia, etc.) is a potentially fruitful but largely untapped methodology for
      understanding sexual behaviors in the population.

PMID- 30115066
TI  - A unified resource for transcriptional regulation in Escherichia coli K-12
      incorporating high-throughput-generated binding data into RegulonDB version 10.0.
AB  - BACKGROUND: Our understanding of the regulation of gene expression has benefited
      from the availability of high-throughput technologies that interrogate the whole
      genome for the binding of specific transcription factors and gene expression
      profiles. In the case of widely used model organisms, such as Escherichia coli K
      12, the new knowledge gained from these approaches needs to be integrated with
      the legacy of accumulated knowledge from genetic and molecular biology
      experiments conducted in the pre-genomic era in order to attain the deepest level
      of understanding possible based on the available data. RESULTS: In this paper, we
      describe an expansion of RegulonDB, the database containing the rich legacy of
      decades of classic molecular biology experiments supporting what we know about
      gene regulation and operon organization in E. coli K-12, to include the genome
      wide dataset collections from 32 ChIP and 19 gSELEX publications, in addition to
      around 60 genome-wide expression profiles relevant to the functional significance
      of these datasets and used in their curation. Three essential features for the
      integration of this information coming from different methodological approaches
      are: first, a controlled vocabulary within an ontology for precisely defining
      growth conditions; second, the criteria to separate elements with enough evidence
      to consider them involved in gene regulation from isolated transcription factor
      binding sites without such support; and third, an expanded computational model
      supporting this knowledge. Altogether, this constitutes the basis for adequately
      gathering and enabling the comparisons and integration needed to manage and
      access such wealth of knowledge. CONCLUSIONS: This version 10.0 of RegulonDB is a
      first step toward what should become the unifying access point for current and
      future knowledge on gene regulation in E. coli K-12. Furthermore, this model
      platform and associated methodologies and criteria can be emulated for gathering
      knowledge on other microbial organisms.

PMID- 30115068
TI  - Suppression of DNA/RNA and protein oxidation by dietary supplement which contains
      plant extracts and vitamins: a randomized, double-blind, placebo-controlled
      trial.
AB  - BACKGROUND: Excessive oxidative stress may impair bio-molecules and cellular
      function. Multi antioxidant supplementation is thought to be more effective than
      a single antioxidant probably through the synergistic or complementary action of
      natural substances that could enhance the prospective effect. METHODS: In order
      to estimate the effect of a plant extract based supplement in apparently healthy
      volunteers' oxidative stress markers, a double-blind and placebo controlled
      intervention was performed. 62 apparently healthy volunteers, overweight with
      medium adherence to the Mediterranean diet, were recruited and randomly allocated
      into two intervention groups (supplement or placebo) for 8 weeks. Basic
      biochemical markers, oxidized LDL (oxLDL), resistance of serum in oxidation,
      protein carbonyls in serum and 8-isoprostane and DNA/RNA damage in urine were
      measured. RESULTS: No differentiation was observed in basic biochemical markers,
      in oxLDL levels as well as in serum resistance against oxidation, during
      intervention in the examined groups. A significant resistance regarding urine
      isoprostanes levels in the supplement group compared to the placebo one, was
      observed. Reduction on DNA/RNA damage and on protein carbonyls levels (almost 30%
      and 20% respectively, at 8 weeks) was detected in volunteers who consumed the
      supplement compared to the control group. CONCLUSION: Consumption of plant
      extract based supplement seems to reduce DNA/RNA and protein oxidation and in
      less extent lipids peroxidation. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier for this study is: NCT02837107.

PMID- 30115071
TI  - Impact of immediate and delayed chilling of raw milk on chemical changes in lipid
      fraction of pasteurized milk.
AB  - BACKGROUND: In many developing countries, milk chilling facilities are not
      available on the farm where milk is produced, rather these are located at the
      distance of 10-12 km. After milking, it takes about 2-3 h to reach milk to the
      chilling facilities. The milk is then chilled and transported to the milk
      processing plants for thermal processing and value addition. In developing
      countries, shelf life of pasteurized milk is only 3 days, as compared to 7-10
      days in developed countries. The factors which are responsible for the shorter
      shelf life of pasteurized milk should be discovered for the improvement of dairy
      sectors of these countries. The magnitude of chemical changes which takes place
      in un-chilled milk and their effect on fatty acids profile, antioxidant status
      and lipid oxidation is not previously studied. METHODS: Raw milk samples of the
      same farm were either rapidly chilled to 4  degrees C immediately or held at room
      temperature (35 +/- 2  degrees C) for 2 h followed by rapid chilling to 4 
      degrees C. Immediately and delayed chilled raw milk samples were stored at 4 
      degrees C for 72 h. Both milk samples were pasteurized at 65  degrees C, filled
      in 250 ml transparent PET bottles and stored at 4  degrees C for 6 days. Fatty
      acid profile, selenium, zinc, total antioxidant capacity, total flavonoid content
      and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, free
      fatty acids, peroxide value and anisidine value were determined at different
      stages of the experiment. This experiment was repeated with milk of same farm for
      at least five times. RESULTS: Storing raw milk at ambient temperature (35 +/- 2 
      degrees C) significantly influenced the pH and lactose content of milk. The loss
      of short-chain fatty acids in delayed chilled milk was 1.19%, 3.27% and 1.60%, as
      compared to immediately chilled raw milk. In delayed chilled milk, loss of C18:1
      and C18:2 after 3 days of storage period was 6.67% and 01.22. In delayed chilled
      milk after 6 days of storage, loss of C18:1 and C18:2 was 7.7% and 1.39%,
      respectively. In immediately chilled milk loss of C18:1 and C18:2 after 3 days of
      storage was 3.48% and 0.64%. In immediately chilled milk loss of C18:1 and C18:2
      after 6 days of storage was 4.57% and 0.9%. Almost 41% vitamin E was lost when
      raw milk was stored at ambient temperature for 2 hrs. About 21% and 7% vitamin E
      was lost in delayed and immediately chilled milk, when samples were analyzed
      immediately after pasteurization. Loss of selenium and zinc contents after 2 h of
      ambient storage of raw milk were 0.43 and 224 MUg/100 g. After 2 h of storage of
      milk at ambient temperature, free fatty acids increased by 0.03% (p < 0.05).
      After 6 days of storage, rise of free fatty acids in immediately and delayed
      chilled milk was 0.06% and 0.14%, respecitively. Rise of 0.13(MeqO2/kg) was
      recorded, when un-chilled raw milk was stored at ambient temperature for 2 h.
      After 3 and 6 days of storage, peroxide value of pasteurized milk (delayed
      chilled) was 0.88 and 1.56 (MeqO2/kg). After 3 and 6 days of storage, peroxide
      value of pasteurized (immediately chilled) was 0.39 and 0.42(MeqO2/kg). After 2
      hrs of ambient storage, 18.41% flavonoids were lost. After 2 hrs of ambient
      storage of raw milk, loss of total antioxidant capacity and DPPH free radical
      scavenging activity was 29.31% and 44.53%. After 6 days of pasteurization, loss
      of total antioxidant capacity and DPPH free radical scavenging activity in
      delayed chilled raw milk was 72.1% and 89.57%. CONCLUSIONS: The findings of this
      investigation showed that delayed chilling of raw milk leads to several
      undesirable chemical changes in lipid fraction of milk.

PMID- 30115070
TI  - Associations of the MTHFR rs1801133 polymorphism with coronary artery disease and
      lipid levels: a systematic review and updated meta-analysis.
AB  - BACKGROUND: The associations of the 5,10-methylenetetrahydrofolate reductase gene
      (MTHFR) rs1801133 polymorphism with coronary artery disease (CAD) and plasma
      lipid levels have been widely investigated, but the results were inconsistent and
      inconclusive. This meta-analysis aimed to clarify the relationships of the
      rs1801133 polymorphism with CAD and plasma lipid levels. METHODS: By searching in
      PubMed, Google Scholar, Web of Science, Cochrane Library, Wanfang, VIP and CNKI
      databases, 123 studies (87,020 subjects) and 65 studies (85,554 subjects) were
      identified for the CAD association analysis and the lipid association analysis,
      respectively. Odds ratio (OR) and standardized mean difference (SMD) were used to
      determine the effects of the rs1801133 polymorphism on CAD risk and lipid levels,
      respectively. RESULTS: The variant T allele of the rs1801133 polymorphism was
      associated with increased risk of CAD under allelic model [OR = 1.11, 95%
      confidence interval (CI) = 1.06-1.17, P < 0.01], additive model (OR = 1.25, 95%
      CI = 1.14-1.37, P < 0.01), dominant model (OR = 1.11, 95% CI = 1.04-1.17, P <
      0.01), and recessive model (OR = 1.22, 95% CI = 1.12-1.32, P < 0.01). The T
      carriers had higher levels of total cholesterol (TC) (SMD = 0.04, 95% CI = 0.01
      0.07, P = 0.02) and low-density lipoprotein cholesterol (LDL-C) (SMD = 0.07, 95%
      CI = 0.01-0.12, P = 0.01) than the non-carriers. CONCLUSIONS: The meta-analysis
      suggested that the T allele of the rs1801133 polymorphism is a risk factor for
      CAD, which is possibly and partly mediated by abnormal lipid levels.

PMID- 30115072
TI  - Preliminary clinical experience with robotic retroperitoneoscopic pancreatic
      surgery.
AB  - BACKGROUNDS: Retroperitoneoscopic surgery has shown advantages in urological
      surgery. However, its application in pancreatic surgery for neoplasm is rare.
      Robotic surgical system with its magnified view and flexible instruments may
      provide a superior alternative to conventional laparoscopic system in
      retroperitoneoscopic surgery. We aimed to evaluate the safety, feasibility, and
      short-term outcomes in a series of patients treated by robotic
      retroperitoneoscopic pancreatic surgery. CASE PRESENTATION: Between March 2016
      and May 2016, four patients with solitary pancreatic neuroendocrine neoplasms
      were treated with robotic retroperitoneoscopic surgery. Prospective collected
      clinical data were retrospectively analyzed. Three patients underwent distal
      pancreatectomy (one combined with resection of left adrenal adenoma), and one
      patient enucleation. The mean operative time was 80 min (range 30-110 min). The
      estimated blood loss was insignificant. There was no conversion to open
      procedure. The mean postoperative hospital stay was 5.25 days (range 4-6 days).
      The mean tumor size was 1.375 cm (range 1.0-1.8 cm) in diameter. All patients'
      blood glucose level returned to normal range within 1 week postoperatively. Two
      patients had pancreatic biochemical leak. No patients underwent subsequent
      treatment, and no recurrence occurred during the 12-month follow-up period.
      CONCLUSIONS: This study preliminarily indicates that robotic retroperitoneoscopic
      pancreatic surgery is safe and feasible for neoplasms in the dorsal portion of
      distal pancreas in selected patients, with some potential advantages of
      straightforward access, simple and fine manipulation, short operative time, and
      fast recovery.

PMID- 30115069
TI  - Abscopal effect of radiotherapy combined with immune checkpoint inhibitors.
AB  - Radiotherapy (RT) is used routinely as a standard treatment for more than 50% of
      patients with malignant tumors. The abscopal effect induced by local RT, which is
      considered as a systemic anti-tumor immune response, reflects the regression of
      non-irradiated metastatic lesions at a distance from the primary site of
      irradiation. Since the application of immunotherapy, especially with immune
      checkpoint inhibitors, can enhance the systemic anti-tumor response of RT, the
      combination of RT and immunotherapy has drawn extensive attention by oncologists
      and cancer researchers. Nevertheless, the exact underlying mechanism of the
      abscopal effect remains unclear. In general, we speculate that the immune
      mechanism of RT is responsible for, or at least associated with, this effect. In
      this review, we discuss the anti-tumor effect of RT and immune checkpoint
      blockade and discuss some published studies on the abscopal effect for this type
      of combination therapy. In addition, we also evaluate the most appropriate time
      window for the combination of RT and immune checkpoint blockade, as well as the
      optimal dose and fractionation of RT in the context of the combined treatment.
      Finally, the most significant purpose of this review is to identify the potential
      predictors of the abscopal effect to help identify the most appropriate patients
      who would most likely benefit from the combination treatment modality.

PMID- 30115073
TI  - Time spent on work-related activities, social activities and time pressure as
      intermediary determinants of health disparities among elderly women and men in 5
      European countries: a structural equation model.
AB  - BACKGROUND: Psychosocial factors shape the health of older adults through complex
      inter-relating pathways. Besides socioeconomic factors, time use activities may
      explain gender inequality in self-reported health. This study investigated the
      role of work-related and social time use activities as determinants of health in
      old age. Specifically, we analysed whether the impact of stress in terms of time
      pressure on health mediated the relationship between work-related time use
      activities (i.e. housework and paid work) on self-reported health. METHODS: We
      applied structural equation models and a maximum-likelihood function to estimate
      the direct and indirect effects of psychosocial factors on health using pooled
      data from the Multinational Time Use Study on 11,168 men and 14,295 women aged
      65+ from Italy, Spain, UK, France and the Netherlands. RESULTS: The fit indices
      for the conceptual model indicated an acceptable fit for both men and women. The
      results showed that socioeconomic status (SES), demographic factors, stress and
      work-related time use activities after retirement had a significant direct
      influence on self-reported health among the elderly, but the magnitude of the
      effects varied by gender. Social activities had a positive impact on self
      reported health but had no significant impact on stress among older men and
      women. The indirect standardized effects of work-related activities on self
      reported health was statistically significant for housework (beta = - 0.006; P <
      0.001 among men and beta = - 0.008; P < 0.001 among women) and paid work (beta =
      0.012; P < 0.01 among men and beta = 0.000; P > 0.05 among women), which implied
      that the paths from paid work and housework on self-reported health via stress
      (mediator) was very weak because their indirect effects were close to zero.
      CONCLUSIONS: Our findings suggest that although stress in terms of time pressure
      has a direct negative effect on health, it does not indirectly influence the
      positive effects of work-related time use activities on self-reported health
      among elderly men and women. The results support the time availability hypothesis
      that the elderly may not have the same time pressure as younger adults after
      retirement.

PMID- 30115075
TI  - Significance of glomerular fibrinogen deposition in children with Henoch
      Schonlein purpura nephritis.
AB  - BACKGROUND: Henoch-Schonlein purpura nephritis (HSPN) is the most common
      pediatric secondary glomerular disease. This study aimed to investigate the
      significance of glomerular fibrinogen (Fib) deposition in children with HSPN.
      METHODS: Eighty-two patients with HSPN were enrolled retrospectively at the
      Children's Hospital of Soochow University from January 2015 to March 2017.
      Patients were divided into groups according to the presence or absence and
      intensity of glomerular Fib deposits, and clinical and pathological features were
      compared among the groups. RESULTS: Glomerular Fib deposition was observed in 64
      children (78.05%), including 1 Fib+/- case (1.22%), 23 Fib+ cases (28.05%), 37
      Fib++ cases (45.12%), and 3 Fib+++ cases (3.66%). Significantly different levels
      of high-sensitivity C-reactive protein (hs-CRP), D-dimer (DD), proportions of
      CD19 + CD23+ cells and urine microalbumin:creatinine ratios (UMA/Cr) were noted
      among the different Fib deposition groups (no, mild and severe). Pairwise
      comparison in multiple groups revealed significantly increased hs-CRP, proportion
      of CD19 + CD23+ cells and UMA/Cr in the severe deposition group compared with the
      mild and no deposition groups, and remarkably increased DD levels were noted in
      the severe and mild deposition groups compared with the no deposition group. The
      degree of glomerular Fib deposition was positively correlated with the degree of
      glomerular IgA deposition, and the incidence of glomerular IgG deposition in the
      severe deposition group was increased compared with the no deposition group.
      CONCLUSION: HSPN children with glomerular Fib deposition, especially those with
      severe Fib deposition, exhibit more severely disordered immunologic function,
      inflammatory reactions and hypercoagulability; glomerular damage in these
      patients may also be more severe.

PMID- 30115074
TI  - What do we know about community-based health worker programs? A systematic review
      of existing reviews on community health workers.
AB  - OBJECTIVE: To synthesize current understanding of how community-based health
      worker (CHW) programs can best be designed and operated in health systems.
      METHODS: We searched 11 databases for review articles published between 1 January
      2005 and 15 June 2017. Review articles on CHWs, defined as non-professional paid
      or volunteer health workers based in communities, with less than 2 years of
      training, were included. We assessed the methodological quality of the reviews
      according to AMSTAR criteria, and we report our findings based on PRISMA
      standards. FINDINGS: We identified 122 reviews (75 systematic reviews, of which
      34 are meta-analyses, and 47 non-systematic reviews). Eighty-three of the
      included reviews were from low- and middle-income countries, 29 were from high
      income countries, and 10 were global. CHW programs included in these reviews are
      diverse in interventions provided, selection and training of CHWs, supervision,
      remuneration, and integration into the health system. Features that enable
      positive CHW program outcomes include community embeddedness (whereby community
      members have a sense of ownership of the program and positive relationships with
      the CHW), supportive supervision, continuous education, and adequate logistical
      support and supplies. Effective integration of CHW programs into health systems
      can bolster program sustainability and credibility, clarify CHW roles, and foster
      collaboration between CHWs and higher-level health system actors. We found gaps
      in the review evidence, including on the rights and needs of CHWs, on effective
      approaches to training and supervision, on CHWs as community change agents, and
      on the influence of health system decentralization, social accountability, and
      governance. CONCLUSION: Evidence concerning CHW program effectiveness can help
      policymakers identify a range of options to consider. However, this evidence
      needs to be contextualized and adapted in different contexts to inform policy and
      practice. Advancing the evidence base with context-specific elements will be
      vital to helping these programs achieve their full potential.

PMID- 30115077
TI  - Environmental factors of diarrhea prevalence among under five children in rural
      area of North Gondar zone, Ethiopia.
AB  - BACKGROUND: In the sub-Saharan countries, many of the children including found in
      health facilities are not having sufficient care of diarrhea. Diarrheal disease
      in these countries is one of the main causes of deaths for under-five children.
      METHODS: A community-based cross-sectional study design was used to collect data
      from May-June, 2016 to determine environmental factors of diarrhea prevalence
      among under five children in North Gondar Zone. Structured interview
      questionnaire and observational checklist were used to collect data. Using
      probability proportion to size, number of households was determined in each
      district. The multivariable binary logistic regression analysis with a 95%
      confidence interval and p < 0.05.was used to identify environmental factors
      associated with childhood diarrheal disease. RESULTS: Of the total 736
      individuals surveyed from 736 households, a total of 163 (22.1%) with [95% CI
      (19.1-25.1)] under -five children had 2 week period diarrhea prevalence. Roof
      material [AOR: 1.99, 95% CI (1.1-3.82)], hand washing facility [AOR: 0.52, 95%CI
      (0.33-0.82)], presence of Latrine facility [AOR: 1.65, 95% CI (1.01-2.72)],
      presence of feces around the pit hole [AOR: 1.65, 95% CI (1.01-2.72)], presence
      of feces around the house compound [AOR: 1.65, 95% CI (1.01-2.72)] and risk of
      contamination of household storage had significant associations with diarrheal
      morbidity. CONCLUSION: The prevalence of childhood diarrheal disease among under 
      five children in rural settings of northwest Ethiopia was high. Type of roof
      material, hand washing facility, presence of Latrine facility, presence of feces
      around the pit hole, presence of feces around the house compound and risk of
      contamination of household storage had significant associations with diarrheal
      morbidity.

PMID- 30115076
TI  - The inverted pattern of circulating miR-221-3p and miR-222-3p associated with
      isolated low HDL-C phenotype.
AB  - BACKGROUND: We investigated the baseline characterization of cardiovascular
      disease (CVD)-derived circulating miR-221-3p/222-3p in isolated low HDL-C
      phenotype (ILHP) to enhance our understanding on their molecular pathological
      pattern prior to disease onset. METHODS: We screened 174 asymptomatic subjects
      with isolated low HDL-C phenotype (n = 88) and normal lipid phenotype (n = 86),
      and detected circulating levels of CVD-derived circulating miR-221-3p/222-3p
      using TaqMan miRNA Real-time PCR detection system. RESULTS: We found the inverted
      pattern of decreased circulating miR-221-3p (0.415 [0.249, 1.004] vs 0.658
      [0.347, 1.534], p = 0.002) versus increased miR-222-3p levels (0.379 [0.101,
      0.701] vs 0.156 [0.043, 0.407], p < 0.001) in ILHP. The baseline levels of
      circulating miR-221-3p and miR-222-3p are correlated with serum HDL-C levels (miR
      221-3p: r = 0.306, p < 0.001; miR-222-3p: r = - 0.201, p = 0.008). Gender-based
      analysis showed female-specific elevation of circulating miR-221-3p in
      asymptomatic individual. Multiple logistic regression analysis showed that
      circulating miR-222-3p is robustly independent factor (adjusted OR = 8.42, 95%CI:
      2.53-27.98, p < 0.001) and significantly improved the performance of the
      predictive clinical model distinguished ILHP from normal lipid phenotype (AUC:
      0.816, 95%CI (0.754, 0.879) vs AUC: 0.771, 95%CI (0.702, 0.840); Z = 2.169, p =
      0.030). Moreover, the increased original Ct ratio of miR-221-3p to miR-222-3p in
      male ILHP (1.003 [0.927, 1.063] vs 0.927 [0.858, 0.967], p < 0.001) significantly
      enhanced the ability to classify male ILHP compared with the male predictive
      clinical model (AUC: 0.851, 95%CI (0.770, 0.933) vs AUC: 0.759, 95%CI (0.659,
      0.859); Z = 2.474, p < 0.05). CONCLUSIONS: The inverted pattern of circulating
      miR-221-3p and miR-222-3p are potentially clinically actionable signature for
      molecular pathology in isolated low HDL-C phenotype.

PMID- 30115078
TI  - KPNA2 promotes metabolic reprogramming in glioblastomas by regulation of c-myc.
AB  - BACKGROUND: Cancer cells maintain energy metabolism mainly by glycolysis, even
      under sufficient oxygen conditions. It gives cancer cells better growth
      advantages under complicated internal environment. KPNA2 is a novel oncogene that
      has received much attention in recent years, but the exact mechanisms of KPNA2 in
      tumorigenesis and progression are largely unknown. Especially its potential roles
      in the metabolic transformation of tumors still remain to be explored. METHODS:
      The expressions of KPNA2 in glioblastoma and normal human brain samples were
      analyzed by immunohistochemical analysis. The activities of key enzymes in
      glycolysis, the production of lactate acid and glucose uptake were investigated
      by colorimetry. GLUT-1 expression was measured by flow cytometry. CCK8 was used
      to examine the cell viability in vitro, and the xenograft models in nude mice
      were established to explore the roles of KPNA2 in vivo. In addition, Co-IP,
      subcellular fractionation, western blot, immunofluorescence and luciferase assay
      were used to investigate the internal connection between KPNA2, c-myc and E2F1.
      RESULTS: In the present study, we found that KPNA2 was highly expressed in the
      glioma compared to the normal brain tissues. Level of KPNA2 was an independent
      predictor of prognosis in the glioma patients. Knockdown of KPNA2 in the
      glioblastoma cell lines U87 and U251 decreased deoxyglucose uptake, activities of
      the key glycolytic enzymes and lactate production. The level of oxidative
      phosphorylation (OXPHOS) was moderately decreased. Additioanlly, tumor
      proliferation and invasiveness were concomitantly downregulated. We have
      identified c-myc as a potential mediator of KPNA2. Aberrant expression of KPNA2
      significantly changed the subcellular distribution of c-myc as well as its
      expression level. E2F1, another key cargo protein of KPNA2, was further
      identified to play a potential role in regulating the transcription of c-myc by
      KPNA2. CONCLUSIONS: Our findings suggested that KPNA2, a potential tumor
      oncogene, performs its function in part via regulating cellular metabolism
      through c-myc signaling axis. It would provide a possible explanation for Warburg
      effect and thus offer a new perspective to the roles of KPNA2 in gliomagenesis.

PMID- 30115079
TI  - Myocardial native T2 measurement to differentiate light-chain and transthyretin
      cardiac amyloidosis and assess prognosis.
AB  - BACKGROUND: To assess the diagnostic and prognosis value of myocardial native T2
      measurement in the distinction between Light-chain (AL) and Transthyretin (ATTR)
      cardiac amyloidosis (CA). METHODS: Forty-four patients with CA (24 AL; 20 ATTR)
      and 40 healthy subjects underwent 1.5 T cardiovascular magnetic resonance (CMR).
      They all underwent T1 and T2 mapping (modified Look-Locker inversion recovery),
      cine and late gadolinium enhancement (LGE) imaging. The Query Amyloid Late
      Enhancement (QALE) score, myocardial native T2, T1 and extra cellular volume
      fraction (ECV) were calculated for all patients. RESULTS: Of the 44 patients, 36
      (82%) exhibited enhancement on LGE images. Mean QALE score of AL (7.9 +/- 6) and
      ATTR (10.5 +/- 5) patients were similar (p = 0.6). Myocardial native T2 was
      significantly (p < 0.0001) higher in AL (63.2 +/- 4.7 ms) than in ATTR (56.2 +/-
      3.1 ms) patients, and both higher (p < 0.001) than healthy subjects (51.1 +/- 3.1
      ms). Myocardial native T2 was highly correlated with myocardial native T1
      (Spearman's rho = 0.79; p < 0.001) and exhibited higher diagnostic performance
      than T1 to separate AL and ATTR patients: the area under curve (AUC) of T2 was
      0.94 (95% CI: 0.86-1, p < 0.001) and the AUC of T1 was 0.77 (95% CI: 0.62-0.91, p
      = 0.03). Myocardial native T2 did not impact overall survival in patients (HR
      1.03 (0.94-1.12); p = 0.53) in contrast to ECV that was the best predictor of
      outcome (HR 1.66 per 0.1 increase in ECV (1.24-2.22); p = 0.0006). CONCLUSIONS:
      Myocardial native T2 significantly is increased in CA, especially in AL patients
      in comparison to ATTR patients. Myocardial native T2 does not impact survival in
      CA patients in contrast to ECV that was the best predictor of outcome. TRIAL
      REGISTRATION: Trial Registration and unique number: CNIL cardio 1778041. Date of
      registration: 20 December 2012.

PMID- 30115080
TI  - Successful treatment of secondary poor graft function post allogeneic
      hematopoietic stem cell transplantation with eltrombopag.
AB  - Poor graft function (PGF) is a life-threatening complication after allogeneic
      hematopoietic stem cell transplantation (allo-HSCT). Current treatment strategies
      include the use of growth factors, CD34+-selected stem cell boost, mesenchymal
      stem cell transfusion, and second allo-HSCT, but these treatments are not
      effective in all patients. Eltrombopag, an oral thrombopoietin receptor agonist,
      which showed promising results in severe aplasia anemia, may be an alternative
      choice for PGF patients. Therefore, we treated 12 patients who responded poorly
      to standard treatments for secondary PGF after allo-HSCT with eltrombopag. The
      median duration was 116 (35-1000) days from transplantation to PGF diagnosis and
      59 (30-180) days from PGF diagnosis to eltrombopag treatment. Eltrombopag was
      started at a dose of 25 mg/d for 3 days and then increased to 50 or 75 mg/d.
      Median treatment duration was 8 (2-23) weeks. Ten patients (83.3%) responded to
      the treatment: 8 achieved complete response (CR), and the remaining 2 achieved
      partial response. In the 10 responding subjects, median platelet count was 18 (5
      27) * 109/L vs 74 (30-117) * 109/L prior to and after treatment. Neutrophil count
      was 0.51 (0.28-0.69) * 109/L vs 1.84 (0.78-4.90) * 109/L. Hemoglobin was 88 (63
      123) vs 101 (78-134) g/L. In the 8 patients who achieved CR, the time from
      eltrombopag initiation to achieving CR was 29 (10-49) days; the response lasted
      until the last follow-up in all 8 CR subjects (10-18 months). The 12-month
      overall survival rate was 83.3%. There was no treatment-related mortality and no
      evidence of cataract, thrombosis, or any other grade 3/4 toxicities.

PMID- 30115081
TI  - Protective effect and related mechanisms of curcumin in rat experimental
      periodontitis.
AB  - BACKGROUND: Curcumin exhibits anti-inflammatory effects and has been suggested as
      a treatment for inflammatory diseases. The aim of this study was to investigate
      the effects of curcumin on the lipopolysaccharide induced inflammatory response
      in rat gingival fibroblasts in vitro and ligation-induced experimental
      periodontitis in vivo, and to speculate the possible anti-inflammatory mechanism
      of curcumin. METHODS: The gingival fibroblasts were incubated with different
      concentrations of curcumin in the absence or presence of lipopolysaccharide
      (LPS). Concentrations of interleukin-1beta(IL-1beta), tumor necrosis factor-alpha
      (TNF-alpha), osteoprotegerin (OPG) and soluble receptor activator of nuclear
      factor kappa-B ligand (RANKL) culture supernatants of rat gingival fibroblasts
      were determined by enzyme linked immunosorbent assay. The nuclear fraction of rat
      gingival fibroblasts was extracted and nuclear factor kappa-B (NF-kappaB)
      activation was assessed by western blotting to elucidate related mechanisms.
      Curcumin was given every two days by oral gavage. The gingival inflammation and
      alveolar bone loss between the first and second molars were observed by
      hematoxylin and eosin staining. Collagen fibers were observed by picro-sirius red
      staining. Alveolar bone loss was assessed by micro-CT analysis. RESULTS: Curcumin
      attenuated the production of IL-1beta and TNF-alpha in rat gingival fibroblasts
      stimulated by LPS, and inhibited the LPS-induced decrease in OPG/sRANKL ratio and
      NF-kappaB activation. Curcumin significantly reduced gingival inflammation and
      modulated collagen fiber and alveolar bone loss in vivo. CONCLUSIONS: curcumin
      modulates inflammatory activity in rat periodontitis by inhibiting NF-kappaB
      activation and decreasing the OPG/sRANKL ratio induced by LPS.

PMID- 30115082
TI  - Music meets robotics: a prospective randomized study on motivation during robot
      aided therapy.
AB  - BACKGROUND: Robots have been successfully applied in motor training during
      neurorehabilitation. As music is known to improve motor function and motivation
      in neurorehabilitation training, we aimed at integrating music creation into
      robotic-assisted motor therapy. We developed a virtual game-like environment with
      music for the arm therapy robot ARMin, containing four different motion training
      conditions: a condition promoting creativity (C+) and one not promoting
      creativity (C-), each in a condition with (V+) and without (V-) a visual display
      (i.e., a monitor). The visual display was presenting the game workspace but not
      contributing to the creative process itself. In all four conditions the therapy
      robot haptically displayed the game workspace. Our aim was to asses the effects
      of creativity and visual display on motivation. METHODS: In a prospective
      randomized single-center study, healthy participants were randomly assigned to
      play two of the four training conditions, either with (V+) or without visual
      display (V-). In the third round, the participants played a repetition of the
      preferred condition of the two first rounds, this time with a new V condition
      (i.e., with or without visual display). For each of the three rounds, motivation
      was measured with the Intrinsic Motivation Inventory (IMI) in the subscales
      interest/enjoyment, perceived choice, value/usefulness, and man-machine-relation.
      We recorded the actual training time, the time of free movement, and the velocity
      profile and administered a questionnaire to measure perceived training time and
      perceived effort. All measures were analysed using linear mixed models.
      Furthermore, we asked if the participants would like to receive the created music
      piece. RESULTS: Sixteen healthy subjects (ten males, six females, mean age: 27.2
      years, standard deviation: 4.1 years) with no known motor or cognitive deficit
      participated. Promotion of creativity (i.e., C+ instead of C-) significantly
      increased the IMI-item interest/enjoyment (p=0.001) and the IMI-item perceived
      choice (p=0.010). We found no significant effects in the IMI-items man-machine
      relation and value/usefulness. Conditions promoting creativity (with or without
      visual display) were preferred compared to the ones not promoting creativity. An
      interaction effect of promotion of creativity and omission of visual display was
      present for training time (p=0.013) and training intensity (p<0.001). No
      differences in relative perceived training time, perceived effort, and perceived
      value among the four training conditions were found. CONCLUSIONS: Promoting
      creativity in a visuo-audio-haptic or audio-haptic environment increases
      motivation in robot-assisted therapy. We demonstrated the feasibility of
      performing an audio-haptic music creation task and recommend to try the system on
      patients with neuromuscular disorders. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT02720341. Registered 25 March 2016,
      https://clinicaltrials.gov/ct2/show/NCT02720341.

PMID- 30115083
TI  - Determining the HPV vaccine schedule for a HIV-infected population in sub Saharan
      Africa, a commentary.
AB  - BACKGROUND: Epidemiological studies have established human papillomavirus (HPV)
      infection as the central cause of invasive cervical cancer (ICC) and its
      precursor lesions. HIV is associated with a higher prevalence and persistence of
      a broader range of high-risk HPV genotypes, which in turn results in a higher
      risk of cervical disease. Recent WHO HPV vaccination schedule recommendations,
      along with the roll out of HAART at an earlier CD4 count within the female HIV
      infected population, may have programmatic implications for sub Saharan Africa.
      This communication identifies research areas, which will need to be addressed for
      determining a HPV vaccine schedule for this population in sub Saharan Africa. A
      review of WHO latest recommendations and the evidence concerning one-dose HPV
      vaccine schedules was undertaken. CONCLUSION: For females >=15 years at the time
      of first dose and immunocompromised and/or HIV-infected, a 3-dose schedule (0, 1
      2, 6 months) is recommended for all three vaccines. There is some evidence that
      there is similar protection against HPV 16 and 18 infection from a single
      vaccination than from two or three doses, however there is no cross protection
      conferred to other genotypes. There is a need for periodic prevalence studies to
      determine the vaccination coverage of bivalent, quadrivalent and nonavalent
      vaccine targeted oncogenic HPV genotypes in women with CIN 3 or ICC at national
      level. In light of the increasing number of sub Saharan HIV-infected girls
      initiating HAART at a CD4 count above 350 mm3, there are a number of clinical,
      virological and public health research gaps to address before a tailored vaccine
      schedule can be established for this population.

PMID- 30115084
TI  - Impact of reducing portion sizes in worksite cafeterias: a stepped wedge
      randomised controlled pilot trial.
AB  - BACKGROUND: Reducing the portion sizes of foods available in restaurants and
      cafeterias is one promising approach to reducing energy intake, but there is
      little evidence of its impact from randomised studies in field settings. This
      study aims to i. examine the feasibility and acceptability, and ii. estimate the
      impact on energy purchased, of reducing portion sizes in worksite cafeterias.
      METHODS: Nine worksites in England were recruited to reduce by at least 10% the
      portion sizes of foods available in their cafeterias from targeted categories
      (main meals, sides, desserts, cakes). In a stepped wedge randomised controlled
      pilot trial, each site was randomised to a date of implementation, staggered
      fortnightly, following a baseline period of four weeks. Impact on energy
      purchased was analysed using generalised linear mixed modelling. We also assessed
      feasibility, acceptability, and fidelity of intervention implementation. RESULTS:
      Data from six of the nine randomised sites were analysed, with three sites
      excluded for not providing sufficient data and/or not implementing the
      intervention. The extent to which the intervention was implemented varied by
      site, with between 6 and 49% of products altered within targeted categories.
      Feedback following the intervention suggested it was broadly acceptable to
      customers and cafeteria staff. For the primary outcome of daily energy (kcal)
      purchased from intervention categories, there was no statistically significant
      change when data from all six sites were pooled: percentage change - 8.9% (95%
      CI: -16.7, - 0.4; p = 0.081). Each of these six sites showed reductions in energy
      purchased, ranging from - 15.6 to - 0.3%, which were borderline statistically
      significant at two sites (respective percentage changes (95% CIs): - 15.6% (-
      26.7, - 2.8); - 14.0% (- 25.0, - 1.2)). Secondary outcome data are suggestive of
      a compensatory increase in energy purchased from food categories not targeted by
      the intervention, with no overall effect observed on energy purchased across all
      categories. CONCLUSIONS: The results of this pilot trial suggest that reducing
      portion sizes could be effective in reducing energy purchased and consumed from
      targeted food categories, and merits investigation in a larger trial. Future
      studies will need to address factors that prevented optimal implementation
      including site dropout and application across a limited range of products. TRIAL
      REGISTRATION: ( ISRCTN52923504 ). Registered on 20th September 2016.

PMID- 30115085
TI  - The discordance between evidence and health policy in the United States: the
      science of translational research and the critical role of diverse stakeholders.
AB  - BACKGROUND: There is often a discordance between health research evidence and
      public health policies implemented by the United States federal government. In
      the process of developing health policy, discordance can arise through subjective
      and objective factors that are unrelated to the value of the evidence itself, and
      can inhibit the use of research evidence. We explore two common types of
      discordance through four illustrative examples and then propose a potential means
      of addressing discordance. DISCUSSION: In Discordance 1, public health
      authorities make recommendations for policy action, yet these are not based on
      high quality, rigorously synthesised research evidence. In Discordance 2,
      evidence-based public health recommendations are ignored or discounted in
      developing United States federal government policy. Both types could lead to
      serious risks of public health and clinical patient harms. We suggest that, to
      mitigate risks associated with these discordances, public health practitioners,
      health policy-makers, health advocates and other key stakeholders should take the
      opportunity to learn or expand their knowledge regarding current research
      methods, as well as improve their skills for appropriately considering the
      strengths and limitations of research evidence. This could help stakeholders to
      adopt a more nuanced approach to developing health policy. Stakeholders should
      also have a more insightful contextual awareness of these discordances and
      understand their potential harms. In Discordance 1, public health organisations
      and authorities need to acknowledge their own historical roles in making public
      health recommendations with insufficient evidence for improving health outcomes.
      In Discordance 2, policy-makers should recognise the larger impact of their
      decision-making based on minimal or flawed evidence, including the potential for
      poor health outcomes at population level and the waste of huge sums. In both
      types of discordance, stakeholders need to consider the impact of their own
      unconscious biases in championing evidence that may not be valid or conclusive.
      CONCLUSION: Public health policy needs to provide evidence-based solutions to
      public health problems, but this is not always done. We discuss some of the
      factors inhibiting evidence-based decision-making in United States federal
      government public health policy and suggest ways these could be addressed.

PMID- 30115086
TI  - Tolerance of preterm formula versus pasteurized donor human milk in very preterm
      infants: a randomized non-inferiority trial.
AB  - BACKGROUND: Human milk (HM) is the best feeding for premature infants. When own
      mother's milk (OMM) is insufficient or unavailable, pasteurized donor human milk
      (PDHM) and preterm formula (PF) are the alternative nutritional sources, but the
      benefits of donor milk over formula are not defined. This study aimed to assess
      whether, in the absence of OMM, the PF could guarantee a feeding tolerance not
      inferior to that seen with the use of PDHM during the first two weeks of life of
      very preterm infants. METHODS: Infants with gestational age (GA) of <=32 weeks
      who started enteral feeding within the first 7 days of life were randomized to
      receive PDHM or PF as a supplement to the OMM insufficient or unavailable. The
      primary outcome was the day of life when full enteral feeding (FEF) of 150
      mL/Kg/d was achieved. RESULTS: Seventy infants were randomized, 35 in the PF
      group (GA 30.2 +/- 1.7 weeks; BW 1342 +/- 275 g), 35 in the PDHM group (GA 30 +/-
      1.9 weeks; BW 1365 +/- 332 g). The time to achieve FEF was the same for infants
      fed with PF and for infants fed with PDHM (12.3 +/- 7.0 days vs 12.8 +/- 6.5).
      CONCLUSIONS: This trial shows that PF could be a valid alternative for the early
      feeding of very preterm infants when OMM is insufficient or unavailable. TRIAL
      REGISTRATION: UMIN000013922 . Date of formal registration: December 31, 2014.

PMID- 30115087
TI  - The effect of the "Follow in my Green Food Steps" programme on cooking behaviours
      for improved iron intake: a quasi-experimental randomized community study.
AB  - BACKGROUND: Nutritional iron deficiency is one of the leading factors for
      disease, disability and death. A quasi-experimental randomized community study in
      South-West Nigeria explored whether a branded behaviour change programme
      increased the use of green leafy vegetables (greens) and iron-fortified bouillon
      cubes in stews for improved iron intake. METHODS: A coinflip assigned the
      intervention to Ile-Ife (Intervention town). Osogbo (Control town) received no
      information. At baseline 602 mother-daughter pairs (daughters aged 12-18) were
      enrolled (Intervention: 300; Control: 302). A Food Frequency Questionnaire
      assessed the addition of cubes and greens to stews, the primary outcome.
      Secondary outcomes were the addition of cubes and greens to soups and changes in
      behavioural determinants measured using the Theory of Planned Behaviour.
      Structural Equation Modelling (SEM) evaluated the impact of the intervention on
      behavioural determinants and behaviour. RESULTS: The data of 527 pairs was used
      (Intervention: 240; Control: 287). The increase in greens added to stews was
      larger in the Intervention town compared to the Control town (MIntervention = 0.3
      [SE = 0.03]; MControl = 0.0 [SE = 0.04], p < 0.001, r = 0.36). Change in iron
      fortified cubes added to stews did not differ between towns (p = 0.07). The
      increase in cubes added to soups was larger in the Intervention town compared to
      the Control Town (MIntervention = 0.9 [SE = 0.2] vs MControl = 0.4 [SE = 0.1], p
      < .0001, r = 0.20). Unexpectedly, change in greens added to soups was larger in
      the Control town compared to the Intervention town (MIntervention = - 0.1 [SE =
      0.1]; MControl = 0.5 [SE = 0.1], p = 0.003, r = 0.15). The intervention
      positively influenced awareness of anaemia and the determinants of behaviour in
      the Intervention town, with hardly any change in the Control town. Baseline SEMs
      could not be established, so no mediation analyses were done. Post-intervention
      SEMs highlighted the role of habit in cooking stews. CONCLUSIONS: The behaviour
      change programme increased the amount of green leafy vegetables added to stews
      and iron-fortified cubes added to soups. Future research should assess the long
      term impact and the efficacy of the programme as it is scaled up and rolled out.

PMID- 30115088
TI  - Development and characterization of an HPV18 detection kit using two novel HPV18
      type-specific monoclonal antibodies.
AB  - BACKGROUND: HPV 18 is one of the most prevalent oncogenic types, only second to
      HPV 16, and included in the licensed vaccines on the market. In this study, we
      describe the production and characterization of a panel of monoclonal antibodies
      (mAb) to HPV18. METHODS: The immunocompetence of 1B1 and 4C2 mAbs for HPV L1
      protein was evaluated by SDS-PAGE analysis, neutralization assays, affinity
      identification, and ELISA. The 1B1 and 4C2 genes were sequenced and analyzed.
      Finally, the detection kit with the two mAbs was assessed for linearity,
      repeatability and specificity. RESULTS: Both mAbs specifically recognized HPV18
      L1 and virus-like particles (VLPs). These mAbs are conformation-neutralizing
      antibodies that have high affinity and type specificity. Based on these
      characteristics of these mAbs, we developed an ELISA kit for specifically
      detecting HPV 18 antigen. We showed that this kit displayed good linearity,
      repeatability and sensitivity for detecting HPV18 L1 pentamer and HPV18 VLP.
      CONCLUSIONS: We characterized two monoclonal neutralizing antibodies for HPV L1
      protein, and developed an ELISA kit for specifically detecting HPV 18 antigen.
      This newly developed kit can be used to monitor the potency of HPV vaccines
      throughout the entire production process as well as preliminary analysis of HPV18
      infections.

PMID- 30115089
TI  - Annual severity increment score as a tool for stratifying patients with Niemann
      Pick disease type C and for recruitment to clinical trials.
AB  - BACKGROUND: Niemann-Pick disease type C (NPC) is a lysosomal storage disease with
      a heterogeneous neurodegenerative clinical course. Multiple therapies are in
      clinical trials and inclusion criteria are currently mainly based on age and
      neurological signs, not taking into consideration differential individual rates
      of disease progression. RESULTS: In this study, we have evaluated a simple
      metric, denoted annual severity increment score (ASIS), that measures rate of
      disease progression and could easily be used in clinical practice. We show that
      ASIS is stable over several years and can be used to stratify patients for
      clinical trials. It achieves greater homogeneity of the study cohort relative to
      age-based inclusion and provides an evidence-based approach for establishing
      inclusion/exclusion criteria. In addition, we show that ASIS has prognostic value
      and demonstrate that treatment with an experimental therapy - acetyl-DL-leucine -
      is associated with a reduction in ASIS scores. CONCLUSION: ASIS has the potential
      to be a useful metric for clinical monitoring, trial recruitment, for prognosis
      and measuring response to therapy.

PMID- 30115090
TI  - Adjuvant vitamin C in cardiac arrest patients undergoing renal replacement
      therapy: an appeal for a higher high-dose.

PMID- 30115091
TI  - Diagnostics of rare disorders: whole-exome sequencing deciphering locus
      heterogeneity in telomere biology disorders.
AB  - BACKGROUND: The telomere biology disorders (TBDs) include a range of multisystem
      diseases characterized by mucocutaneous symptoms and bone marrow failure. In
      dyskeratosis congenita (DKC), the clinical features of TBDs stem from the
      depletion of crucial stem cell populations in highly proliferative tissues,
      resulting from abnormal telomerase function. Due to the wide spectrum of clinical
      presentations and lack of a conclusive laboratory test it may be challenging to
      reach a clinical diagnosis, especially if patients lack the pathognomonic
      clinical features of TBDs. METHODS: Clinical sequencing was performed on a cohort
      of patients presenting with variable immune phenotypes lacking molecular
      diagnoses. Hypothesis-free whole-exome sequencing (WES) was selected in the
      absence of compelling diagnostic hints in patients with variable immunological
      and haematological conditions. RESULTS: In four patients belonging to three
      families, we have detected five novel variants in known TBD-causing genes (DKC1,
      TERT and RTEL1). In addition to the molecular findings, they all presented
      shortened blood cell telomeres. These findings are consistent with the displayed
      TBD phenotypes, addressing towards the molecular diagnosis and subsequent
      clinical follow-up of the patients. CONCLUSIONS: Our results strongly support the
      utility of WES-based approaches for routine genetic diagnostics of TBD patients
      with heterogeneous or atypical clinical presentation who otherwise might remain
      undiagnosed.

PMID- 30115092
TI  - Head-to-head comparison between the EQ-5D-5L and the EQ-5D-3L in general
      population health surveys.
AB  - BACKGROUND: The EQ-5D has been frequently used in national health surveys. This
      study is a head-to-head comparison to assess how expanding the number of levels
      from three (EQ-5D-3L) to five in the new EQ-5D-5L version has improved its
      distribution, discriminatory power, and validity in the general population.
      METHODS: A representative sample (N = 7554) from the Catalan Health Interview
      Survey 2011-2012, aged >=18, answered both EQ-5D versions, and we evaluated the
      response redistribution and inconsistencies between them. To assess validity of
      this redistribution, we calculated the mean of the Visual Analogue Scale (VAS),
      which measures perceived health. The discriminatory power was examined with
      Shannon Indices, calculated for each dimension separately. Spanish preference
      value sets were applied to obtain utility indices, examining their distribution
      with statistics of central tendency and dispersion. We estimated the proportion
      of individuals reporting the best health state in EQ-5D-5L and EQ-5D-3L within
      groups of specific chronic conditions and their VAS mean. RESULTS: A very small
      reduction in the percentage of individuals with the best health state was
      observed, from 61.8% in EQ-5D-3L to 60.8% in EQ-5D-5L. In contrast, a large
      proportion of individuals reporting extreme problems in the 3 L version moved to
      severe problems (level 4) in the 5 L version, particularly for pain/discomfort
      (75.5%) and anxiety/depression (66.4%). The average proportion of inconsistencies
      was 0.9%. The pattern of the perceived health VAS mean confirmed the hypothesis
      established a priori, supporting the validity of the observed redistribution.
      Shannon index showed that absolute informativity was higher in the 5 L version
      for all dimensions. The means (SD) of the Spanish EQ-5D-3L and EQ-5D-5L indices
      were 0.87 (0.25) and 0.89 (0.22). The proportion of individuals with the best
      health state within each specific chronic condition was very similar, regardless
      of the EQ-5D version (<= 30% in half of the 28 chronic conditions). CONCLUSION:
      Although the proportion of individuals with the best possible health state is
      still very high, our findings support that the increase of levels provided by the
      EQ-5D-5L contributed to the validity and discriminatory power of this new version
      to measure health in general population, as in the national health surveys.

PMID- 30115093
TI  - Bilateral reaching deficits after unilateral perinatal ischemic stroke: a
      population-based case-control study.
AB  - BACKGROUND: Detailed kinematics of motor impairment of the contralesional
      ("affected") and ipsilesional ("unaffected") limbs in children with hemiparetic
      cerebral palsy are not well understood. We aimed to 1) quantify the kinematics of
      reaching in both arms of hemiparetic children with perinatal stroke using a
      robotic exoskeleton, and 2) assess the correlation of kinematic reaching
      parameters with clinical motor assessments. METHODS: This prospective, case
      control study involved the Alberta Perinatal Stroke Project, a population-based
      research cohort, and the Foothills Medical Center Stroke Robotics Laboratory in
      Calgary, Alberta over a four year period. Prospective cases were collected
      through the Calgary Stroke Program and included term-born children with magnetic
      resonance imaging confirmed perinatal ischemic stroke and upper extremity
      deficits. Control participants were recruited from the community. Participants
      completed a visually guided reaching task in the KINARM robot with each arm
      separately, with 10 parameters quantifying motor function. Kinematic measures
      were compared to clinical assessments and stroke type. RESULTS: Fifty children
      with perinatal ischemic stroke (28 arterial, mean age: 12.5 +/- 3.9 years; 22
      venous, mean age: 11.5 +/- 3.8 years) and upper extremity deficits were compared
      to healthy controls (n = 147, mean age: 12.7 +/- 3.9 years). Perinatal stroke
      groups demonstrated contralesional motor impairments compared to controls when
      reaching out (arterial = 10/10, venous = 8/10), and back (arterial = 10/10,
      venous = 6/10) with largest errors in reaction time, initial direction error,
      movement length and time. Ipsilesional impairments were also found when reaching
      out (arterial = 7/10, venous = 1/10) and back (arterial = 6/10). The arterial
      group performed worse than venous on both contralesional and ipsilesional
      parameters. Contralesional reaching parameters showed modest correlations with
      clinical measures in the arterial group. CONCLUSIONS: Robotic assessment of
      reaching behavior can quantify complex, upper limb dysfunction in children with
      perinatal ischemic stroke. The ipsilesional, "unaffected" limb is often abnormal
      and may be a target for therapeutic interventions in stroke-induced hemiparetic
      cerebral palsy.

PMID- 30115094
TI  - Research, diagnosis and education in inborn errors of metabolism in Colombia: 20
      years' experience from a reference center.
AB  - The use of specialized centers has been the main alternative for an appropriate
      diagnosis, management and follow up of patients affected by inborn errors of
      metabolism (IEM). These centers facilitate the training of different
      professionals, as well as the research at basic, translational and clinical
      levels. Nevertheless, few reports have described the experience of these centers
      and their local and/or global impact in the study of IEM. In this paper, we
      describe the experience of a Colombian reference center for the research,
      diagnosis, training and education on IEM. During the last 20 years, important
      advances have been achieved in the clinical knowledge of these disorders, as well
      as in the local availability of several diagnosis tests. Organic acidurias have
      been the most frequently detected diseases, followed by aminoacidopathies and
      peroxisomal disorders. Research efforts have been focused in the production of
      recombinant proteins in microorganisms towards the development of new enzyme
      replacement therapies, the design of gene therapy vectors and the use of
      bioinformatics tools for the understanding of IEM. In addition, this center has
      participated in the education and training of a large number professionals at
      different levels, which has contributed to increase the knowledge and divulgation
      of these disorders along the country. Noteworthy, in close collaboration with
      patient advocacy groups, we have participated in the discussion and construction
      of initiatives for the inclusion of diagnosis tests and treatments in the health
      system.

PMID- 30115096
TI  - Healthcare resource utilization in the management of hypophosphatasia in three
      patients displaying a spectrum of manifestations.
AB  - BACKGROUND: Hypophosphatasia (HPP) is a rare, heterogeneous disease caused by low
      tissue-nonspecific alkaline phosphatase activity and associated with a range of
      signs and symptoms, including bone mineralization defects, respiratory problems,
      seizures, premature tooth loss, and fractures. Data from patients with HPP and
      their healthcare resource utilization are lacking. We evaluated healthcare
      utilization for 3 patients with differing severities of HPP. RESULTS: Patient 1
      had perinatal HPP (received enzyme replacement therapy asfotase alfa under a
      compassionate use program), Patient 2 had infantile HPP, and Patient 3 had
      childhood HPP. Healthcare resources used in the National Health Service, England,
      were identified from coded activities in the hospital database and detailed
      medical records. These data showed that healthcare utilization was directly
      related to disease severity. Patient 1 had respiratory complications
      necessitating prolonged admission for ventilation from birth. Over 2.5 years,
      this patient was hospitalized 725 days, with visits from 16 specialists. Patient
      2 had HPP-associated signs and symptoms starting in infancy, was treated for
      craniosynostosis, experienced multiple fractures, and required outpatient
      management for > 18 years. Patient 3 developed signs and symptoms of HPP in
      childhood and received outpatient and day case treatment for dental, orthopedic,
      and cardiovascular problems over 24 years. Healthcare utilization varied with
      severity and complexity of disease manifestations between these patients.
      CONCLUSIONS: With the recent approval of asfotase alfa for HPP, data from this
      analysis may help mobilize multidisciplinary healthcare resources for management
      of HPP by elucidating healthcare resource needs of patients who show a spectrum
      of clinical manifestations of HPP.

PMID- 30115095
TI  - Low fertility may be a significant determinant of ovarian cancer worldwide: an
      ecological analysis of cross- sectional data from 182 countries.
AB  - BACKGROUND: Ageing, socioeconomic level, obesity, fertility, relaxed natural
      selection and urbanization have been postulated as the risk factors of ovarian
      cancer (OC56). We sought to identify which factor plays the most significant role
      in predicting OC56 incidence rate worldwide. METHODS: Bivariate correlation
      analysis was performed to assess the relationships between country-specific
      estimates of ageing (measured by life expectancy), GDP PPP (Purchasing power
      parity), obesity prevalence, fertility (indexed by the crude birth rate),
      opportunity for natural selection (Ibs) and urbanization. Partial correlation was
      used to compare contribution of different variables. Fisher A-to-Z was used to
      compare the correlation coefficients. Multiple linear regression (Enter and
      Stepwise) was conducted to identify significant determinants of OC56 incidence.
      ANOVA with post hoc Bonferroni analysis was performed to compare differences
      between the means of OC56 incidence rate and residuals of OC56 standardised on
      fertility and GDP respectively between the six WHO regions. RESULTS: Bivariate
      analyses revealed that OC56 was significantly and strongly correlated to ageing,
      GDP, obesity, low fertility, Ibs and urbanization. However, partial correlation
      analysis identified that fertility and ageing were the only variables that had a
      significant correlation to OC56 incidence when the other five variables were kept
      statistically constant. Fisher A-to-Z revealed that OC56 had a significantly
      stronger correlation to low fertility than to ageing. Stepwise linear regression
      analysis only identified fertility as the significant predictor of OC56. ANOVA
      showed that, between the six WHO regions, multiple mean differences of OC56
      incidence were significant, but all disappeared when the contributing effect of
      fertility on OC56 incidence rate was removed. CONCLUSIONS: Low fertility may be
      the most significant determining predictor of OC56 incidence worldwide.

PMID- 30115098
TI  - Bartter syndrome-like phenotype in a patient with diabetes: a case report.
AB  - BACKGROUND: Bartter's syndrome is a rare genetic tubulopathy affecting the loop
      of Henle leading to salt wasting. It is commonly seen in utero or in early
      neonatal period. Rare cases of acquired Bartter's syndrome are reported in
      association with infections like tuberculosis, granulomatous conditions like
      sarcoidosis, autoimmune diseases, and drugs. The mainstay of management includes
      potassium, calcium, and magnesium supplementation. CASE PRESENTATION: We report
      the case of a 62-year-old Sri Lankan Sinhalese man with diabetes and hypertension
      presenting with generalized weakness with clinical evidence of proximal myopathy.
      He was severely hypokalemic with high urinary potassium excretion and
      hypochloremic metabolic alkalosis. He poorly responded to intravenously
      administered potassium supplements. A diagnosis of idiopathic Bartter-like
      phenotype was made. He responded well to spironolactone and indomethacin.
      CONCLUSIONS: Patients presenting with body weakness need serum potassium
      estimation. Acquired Bartter's syndrome although rare, should be ruled out in
      those with hypokalemia and metabolic alkalosis with increased urinary potassium
      loss with poor response to potassium replacement.

PMID- 30115097
TI  - Chromosome-scale comparative sequence analysis unravels molecular mechanisms of
      genome dynamics between two wheat cultivars.
AB  - BACKGROUND: Recent improvements in DNA sequencing and genome scaffolding have
      paved the way to generate high-quality de novo assemblies of pseudomolecules
      representing complete chromosomes of wheat and its wild relatives. These
      assemblies form the basis to compare the dynamics of wheat genomes on a megabase
      scale. RESULTS: Here, we provide a comparative sequence analysis of the 700
      megabase chromosome 2D between two bread wheat genotypes-the old landrace Chinese
      Spring and the elite Swiss spring wheat line 'CH Campala Lr22a'. Both chromosomes
      were assembled into megabase-sized scaffolds. There is a high degree of sequence
      conservation between the two chromosomes. Analysis of large structural variations
      reveals four large indels of more than 100 kb. Based on the molecular signatures
      at the breakpoints, unequal crossing over and double-strand break repair were
      identified as the molecular mechanisms that caused these indels. Three of the
      large indels affect copy number of NLRs, a gene family involved in plant
      immunity. Analysis of SNP density reveals four haploblocks of 4, 8, 9 and 48 Mb
      with a 35-fold increased SNP density compared to the rest of the chromosome. Gene
      content across the two chromosomes was highly conserved. Ninety-nine percent of
      the genic sequences were present in both genotypes and the fraction of unique
      genes ranged from 0.4 to 0.7%. CONCLUSIONS: This comparative analysis of two high
      quality chromosome assemblies enabled a comprehensive assessment of large
      structural variations and gene content. The insight obtained from this analysis
      will form the basis of future wheat pan-genome studies.

PMID- 30115099
TI  - Space-time clustering and associated risk factors of pulmonary tuberculosis in
      southwest China.
AB  - BACKGROUND: Pulmonary tuberculosis (PTB,both smear positive and smear negative)
      is an airborne infectious disease of major public health concern in China and
      other parts of the world where PTB endemicity is reported. This study aims at
      identifying PTB spatio-temporal clusters and associated risk factors in Zhaotong
      prefecture-level city, located in southwest China, where the PTB notification
      rate was higher than the average rate in the entire country. METHODS: Space-time
      scan statistics were carried out using PTB registered data in the nationwide TB
      online registration system from 2011 to 2015, to identify spatial clusters. PTB
      patients diagnosed between October 2015 and February 2016 were selected and a
      structured questionnaire was administered to collect a set of variables that
      includes socio-economic status, behavioural characteristics, local environmental
      and biological characteristics. Based on the discovery of detailed town-level
      spatio-temporal PTB clusters, we divided selected subjects into two groups
      including the cases that resides within and outside identified clusters. Then,
      logistic regression analysis was applied comparing the results of variables
      between the two groups. RESULTS: A total of 1508 subjects consented and
      participated in the survey. Clusters for PTB cases were identified in 38 towns
      distributed over south-western Zhaotong. Logistic regression analysis showed that
      history of chronic bronchitis (OR = 3.683, 95% CI: 2.180-6.223), living in an
      urban area (OR = 5.876, 95% CI: 2.381-14.502) and using coal as the main fuel (OR
      = 9.356, 95% CI: 5.620-15.576) were independently associated with clustering.
      While, not smoking (OR = 0.340, 95% CI: 0.137-0.843) is the protection factor of
      spatial clustering. CONCLUSIONS: We found PTB specially clustered in south
      western Zhaotong. The strong associated factors influencing the PTB spatial
      cluster including: the history of chronic bronchitis, living in the urban area,
      smoking and the use of coal as the main fuel for cooking and heating. Therefore,
      efforts should be made to curtail these associated factors.

PMID- 30115100
TI  - Impact of transposable elements on genome structure and evolution in bread wheat.
AB  - BACKGROUND: Transposable elements (TEs) are major components of large plant
      genomes and main drivers of genome evolution. The most recent assembly of
      hexaploid bread wheat recovered the highly repetitive TE space in an almost
      complete chromosomal context and enabled a detailed view into the dynamics of TEs
      in the A, B, and D subgenomes. RESULTS: The overall TE content is very similar
      between the A, B, and D subgenomes, although we find no evidence for bursts of TE
      amplification after the polyploidization events. Despite the near-complete
      turnover of TEs since the subgenome lineages diverged from a common ancestor, 76%
      of TE families are still present in similar proportions in each subgenome.
      Moreover, spacing between syntenic genes is also conserved, even though syntenic
      TEs have been replaced by new insertions over time, suggesting that distances
      between genes, but not sequences, are under evolutionary constraints. The TE
      composition of the immediate gene vicinity differs from the core intergenic
      regions. We find the same TE families to be enriched or depleted near genes in
      all three subgenomes. Evaluations at the subfamily level of timed long terminal
      repeat-retrotransposon insertions highlight the independent evolution of the
      diploid A, B, and D lineages before polyploidization and cases of concerted
      proliferation in the AB tetraploid. CONCLUSIONS: Even though the intergenic space
      is changed by the TE turnover, an unexpected preservation is observed between the
      A, B, and D subgenomes for features like TE family proportions, gene spacing, and
      TE enrichment near genes.

PMID- 30115101
TI  - Linking the International Wheat Genome Sequencing Consortium bread wheat
      reference genome sequence to wheat genetic and phenomic data.
AB  - The Wheat@URGI portal has been developed to provide the international community
      of researchers and breeders with access to the bread wheat reference genome
      sequence produced by the International Wheat Genome Sequencing Consortium. Genome
      browsers, BLAST, and InterMine tools have been established for in-depth
      exploration of the genome sequence together with additional linked datasets
      including physical maps, sequence variations, gene expression, and genetic and
      phenomic data from other international collaborative projects already stored in
      the GnpIS information system. The portal provides enhanced search and browser
      features that will facilitate the deployment of the latest genomics resources in
      wheat improvement.

PMID- 30115102
TI  - The prevalence of Lynch syndrome in women with endometrial cancer: a systematic
      review protocol.
AB  - BACKGROUND: Lynch syndrome is the most common inherited cancer syndrome, which
      predisposes individuals to a number of different cancers, principally colorectal
      and endometrial cancer. The early diagnosis of Lynch syndrome enables colorectal
      surveillance, which has been shown to save lives through the detection and
      removal of premalignant polyps and earlier detection of invasive disease.
      Endometrial cancer, which is often the sentinel cancer in women, provides an
      opportunity to diagnose Lynch syndrome and thus enable colorectal surveillance as
      well as the cascade testing for Lynch syndrome in other family members. These
      potential benefits have led to a call for the universal screening of women with
      endometrial cancer for Lynch syndrome, a practice that is now commonplace in
      colorectal cancer. Healthcare providers and clinicians are however restricted by
      insufficient knowledge about the prevalence of Lynch syndrome in women with
      endometrial cancer, with estimates varying as widely as 1-10%. The aim of this
      study is to perform a systematic review with a meta-analysis of the current
      literature base in order to estimate the prevalence of Lynch syndrome among women
      with endometrial cancer to inform this discussion. METHODS: Medline, Embase,
      Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Methodology
      Register, NHS Health and Technology Assessment Database and the Web of Science
      will be systematically searched for relevant studies via the Ovid platform. Two
      authors will review the titles and abstracts independently, with discrepancy
      settled by a third author. Data extraction will be completed to record
      demographic, pathological and clinical data, as well as the diagnostic methods
      used for estimating the prevalence of Lynch syndrome in women with endometrial
      cancer. Bias will be assessed and recorded using the Newcastle-Ottawa Scale and
      that of the International Cochrane Collaboration. Dependent on the heterogeneity
      of the data, we aim to produce a cumulative incidence in addition to subgroup
      analyses as to investigate secondary outcomes. DISCUSSION: The aim of this
      systematic review is to provide a robust estimate of the prevalence of Lynch
      syndrome in women with endometrial cancer. This will enable resource allocation
      and decision-making regarding the appropriateness of screening all women, or
      certain women, with endometrial cancer for Lynch syndrome. Such a policy could
      enable the earlier diagnosis of Lynch syndrome in women and, through the
      application of colorectal cancer surveillance, improve their survival outcomes.
      SYSTEMATIC REVIEW REGISTRATION: This systematic review has been registered on
      PROSPERO (ref CRD42017081707 ).

PMID- 30115103
TI  - Intravenous ivabradine versus placebo in patients with low cardiac output
      syndrome treated by dobutamine after elective coronary artery bypass surgery: a
      phase 2 exploratory randomized controlled trial.
AB  - BACKGROUND: Low cardiac output syndrome (LCOS) is a severe condition which can
      occur after cardiac surgery, especially among patients with pre-existing left
      ventricular dysfunction. Dobutamine, its first-line treatment, is associated with
      sinus tachycardia. This study aims to assess the ability of intravenous
      ivabradine to decrease sinus tachycardia associated with dobutamine infused for
      LCOS after coronary artery bypass graft (CABG) surgery. METHODS: In a phase 2,
      multi-center, single-blind, randomized controlled trial, patients with left
      ventricular ejection fraction below 40% presenting sinus tachycardia of at least
      100 beats per minute (bpm) following dobutamine infusion for LCOS after CABG
      surgery received either intravenous ivabradine or placebo (three ivabradine for
      one placebo). Treatment lasted until dobutamine weaning or up to 48 h. The
      primary endpoint was the proportion of patients achieving a heart rate (HR) in
      the 80- to 90-bpm range. Secondary endpoints were invasive and non-invasive
      hemodynamic parameters and arrhythmia events. RESULTS: Nineteen patients were
      included. More patients reached the primary endpoint in the ivabradine than in
      the placebo group (13 (93%) versus 2 (40%); P = 0.04). Median times to reach
      target HR were 1.0 h in the ivabradine group and 5.7 h in the placebo group.
      Ivabradine decreased HR (112 to 86 bpm, P <0.001) while increasing cardiac index
      (P = 0.02), stroke volume (P <0.001), and systolic blood pressure (P = 0.03). In
      the placebo group, these parameters remained unchanged from baseline. In the
      ivabradine group, five patients (36%) developed atrial fibrillation (AF) and one
      (7%) was discontinued for sustained AF; two (14%) were discontinued for
      bradycardia. CONCLUSION: Intravenous ivabradine achieved effective and rapid
      correction of sinus tachycardia in patients who received dobutamine for LCOS
      after CABG surgery. Simultaneously, stroke volume and systolic blood pressure
      increased, suggesting a beneficial effect of this treatment on tissue perfusion.
      TRIAL REGISTRATION: European Clinical Trials Database: EudraCT 2009-018175-14 .
      Registered February 2, 2010.

PMID- 30115104
TI  - Partial factorial trials: comparing methods for statistical analysis and economic
      evaluation.
AB  - BACKGROUND: Partial factorial trials compare two or more pairs of treatments on
      overlapping patient groups, randomising some (but not all) patients to more than
      one comparison. The aims of this research were to compare different methods for
      conducting and analysing economic evaluations on partial factorial trials and
      assess the implications of considering factors simultaneously rather than drawing
      independent conclusions about each comparison. METHODS: We estimated total costs
      and quality-adjusted life years (QALYs) within 10 years of surgery for 2252
      patients in the Knee Arthroplasty Trial who were randomised to one or more
      comparisons of different surgical types. We compared three analytical methods: an
      "at-the-margins" analysis including all patients randomised to each comparison
      (assuming no interaction); an "inside-the-table" analysis that included
      interactions but focused on those patients randomised to two comparisons; and a
      Bayesian vetted bootstrap, which used results from patients randomised to one
      comparison as priors when estimating outcomes for patients randomised to two
      comparisons. Outcomes comprised incremental costs, QALYs and net benefits.
      RESULTS: Qualitative interactions were observed for costs, QALYs and net
      benefits. Bayesian bootstrapping generally produced smaller standard errors than
      inside-the-table analysis and gave conclusions that were consistent with at-the
      margins analysis, while allowing for these interactions. By contrast, inside-the
      table gave different conclusions about which intervention had the highest net
      benefits compared with other analyses. CONCLUSIONS: All analyses of partial
      factorial trials should explore interactions and assess whether results are
      sensitive to assumptions about interactions, either as a primary analysis or as a
      sensitivity analysis. For partial factorial trials closely mirroring routine
      clinical practice, at-the-margins analysis may provide a reasonable estimate of
      average costs and benefits for the whole trial population, even in the presence
      of interactions. However, such conclusions will be misleading if there are large
      interactions or if the proportion of patients allocated to different treatments
      differs markedly from what occurs in clinical practice. The Bayesian bootstrap
      provides an alternative to at-the-margins analysis for analysing clinical or
      economic endpoints from partial factorial trials, which allows for interactions
      while making use of the whole sample. The same techniques could be applied to
      analyses of clinical endpoints. TRIAL REGISTRATION: ISRCTN, ISRCTN45837371 .
      Registered on 25 April 2003.

PMID- 30115105
TI  - High-frequency ultrasound of the skin in systemic sclerosis: an exploratory study
      to examine correlation with disease activity and to define the minimally
      detectable difference.
AB  - BACKGROUND: Thickened skin is a major clinical feature in patients with systemic
      sclerosis (SSc). We investigated changes of skin thickness in patients with SSc
      using both high frequency ultrasound (HFU) and the modified Rodnan skin score
      (mRSS) to evaluate the feasibility of application of HFU in skin involvement and
      the relationship between HFU and clinical profiles. METHODS: We recruited 31
      consecutive patients with SSc and 31 age-matched and sex-matched healthy controls
      in this prospective, cross-sectional study. Skin thickness was measured by an 18
      MHz ultrasonic probe at five different skin sites. Total skin thickness (TST) and
      skin thickness using categorical mRSS scores were recorded and compared to HFU.
      The European Scleroderma Trial and Research (EUSTAR) group Disease Activity Index
      (EUSTAR-DAI) and other clinical manifestations were assessed and analyzed.
      RESULTS: TST in patients with SSc was thicker than in healthy controls (P <
      0.001), and correlated positively with total mRSS and the EUSTAR-DAI and
      correlated negatively with disease duration (P < 0.05). Patients with higher TST
      had higher EUSTAR-DAI, mRSS, C-reactive protein (CRP) and lower diffusing
      capacity of the lung for carbon monoxide (DLCO) (P < 0.05). Even in patients who
      on clinical assessment were assigned an mRSS that suggested the skin thickness
      was normal. This was also true to mRSS locally of 1 and 2 (P < 0.01). The area
      under the receiver operator characteristic (ROC) curve was 0.831 and yielded
      sensitivity of 77.4% and specificity of 87.1% at the predicted probability of 7.4
      mm as the optimal cutoff point to access skin thickness. CONCLUSIONS: In the
      study, HFU was able to measure skin thickness, it correlated quantitatively with
      a valid measure of SSc activity, and a minimal detectable difference was
      identified.

PMID- 30115107
TI  - A methodological approach to identify the most reliable human milk collection
      method for compositional analysis: a systematic review protocol.
AB  - BACKGROUND: Breast milk composition has been reported to vary significantly
      between individual women and between different populations. However, the
      composition is also known to vary within the same woman between different days,
      within the same day, and even across the same feed. Therefore, it is unclear to
      what extent variations in composition are due to variations in sampling
      methodology between studies. The purpose of this systematic review is to compare
      the results obtained for breast milk macronutrient composition between studies
      utilizing different sampling methodologies and to use this as a basis to
      determine the most robust and consistent sampling approach as an alternative to
      full expression (gold standard). METHODS: The EMBASE, MEDLINE/PubMed, Cochrane
      Library, Scopus, Web of Science, and ProQuest Dissertations and Theses Global
      databases will be searched for relevant articles. Observational studies,
      including cross-sectional, comparative cohort, and longitudinal cohort studies
      which involve lactating women who are breastfeeding (exclusively or not) or
      expressing (manually or using a breast pump) at any lactation stage will be
      included. This review will compare different methods of breast milk collection
      used in research studies which report macronutrient levels (protein, fat,
      lactose). Two review authors will independently screen titles and abstracts of
      studies identified by the literature search to determine articles for the full
      text screening. Quality assessment of included articles will be conducted
      independently by two review authors using the Newcastle-Ottawa scale. DISCUSSION:
      It is important to identify the most reliable and practical method of human milk
      collection which best represents the average composition of the milk that is
      being consumed by the infant. This systematic review will be critical for
      ensuring that we determine a robust and consistent sampling approach to use in
      future studies of evaluating breast milk composition in a larger population.
      Identifying a recommended standard collection protocol will also provide more
      opportunities for sharing and combining data from different research groups, thus
      enhancing replicability and knowledge in the field. SYSTEMATIC REVIEW
      REGISTRATION: PROSPERO CRD42017072563.

PMID- 30115106
TI  - Serum biomarker for diagnostic evaluation of pulmonary arterial hypertension in
      systemic sclerosis.
AB  - BACKGROUND: Systemic sclerosis-associated pulmonary arterial hypertension (SSc
      PAH) is one of the leading causes of death in SSc. Identification of a serum
      based proteomic diagnostic biomarker for SSc-PAH would allow for rapid non
      invasive screening and could positively impact patient survival. Identification
      and validation of novel proteins could potentially facilitate the identification
      of SSc-PAH, and might also point to important protein mediators in pathogenesis.
      METHODS: Thirteen treatment-naive SSc-PAH patients had serum collected at time of
      diagnosis and were used as the discovery cohort for the protein-expression
      biomarker. Two proteins, Midkine and Follistatin-like 3 (FSTL3) were then
      validated by enzyme-linked immunosorbent assays. Midkine and FSTL3 were tested in
      combination to identify SSc-PAH and were validated in two independent cohorts of
      SSc-PAH (n = 23, n = 11). RESULTS: Eighty-two proteins were found to be
      differentially regulated in SSc-PAH sera. Two proteins (Midkine and FSTL3) were
      also shown to be elevated in publicly available data and their expression was
      evaluated in independent cohorts. In the validation cohorts, the combination of
      Midkine and FSTL3 had an area under the receiver operating characteristic curve
      (AUC) of 0.85 and 0.92 with respective corresponding measures of sensitivity of
      76% and 91%, and specificity measures of 76% and 80%. CONCLUSIONS: These findings
      indicate that there is a clear delineation between overall protein expression in
      sera from SSc patients and those with SSc-PAH. The combination of Midkine and
      FSTL3 can serve as an SSc-PAH biomarker and are potential drug targets for this
      rare disease population.

PMID- 30115108
TI  - Hemodynamic management of critically ill burn patients: an international survey.

PMID- 30115109
TI  - Indicators of deterioration in young adults with serious mental illness: a
      systematic review protocol.
AB  - BACKGROUND: The first signs of serious mental illnesses (SMIs) including
      schizophrenia, bipolar disorder and major depression are likely to occur before
      the age of 25. The combination of high prevalence of severe mental health
      symptoms, inability to recognise mental health deterioration and increased
      likelihood of comorbidity in a complex transitional young group makes detecting
      deterioration paramount. Whilst studies have examined physical and mental health
      deterioration in adults, no systematic review has examined the indicators of
      mental and physical deterioration in young adults with SMI. The study aim is to
      systematically review the existing evidence from observational studies that
      examine the indicators of mental and physical deterioration in young adults with
      SMI and highlight gaps in knowledge to inform future research. METHODS: Seven
      databases including CINHAL, MEDLINE, Embase, PsycINFO, Health Management
      Information Consortium, Cochrane databases and Web of Science will be searched
      against five main facets (age, serious mental illness, sign, deterioration and
      patient) and a subsequent comprehensive list of search terms. Searches will be
      run individually in each database to reflect each unique set of relevant subject
      headings and appropriate MeSH terms. Inclusion and exclusion criteria were
      developed and refined by the research team. Two reviewers will participate in
      each search stage including abstract/title and full text screening, data
      extraction and appraisal, to ensure reliability. A narrative synthesis of the
      data will also be conducted. DISCUSSION: This systematic review will likely make
      a significant contribution to the field of mental health and help inform future
      research pertaining to interventions that help highlight deteriorating patients.
      This may vary depending on the patient group, mental illness or deterioration
      type. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42017075755.

PMID- 30115110
TI  - Effects of transitional care on self-care, readmission rates, and quality of life
      in adult patients with systemic lupus erythematosus: a randomized controlled
      trial.
AB  - BACKGROUND: Lack of adequate self-care, frequent admissions, and poor quality of
      life are common and serious problems in adult patients with systemic lupus
      erythematosus (SLE). Some studies have revealed that transitional care is
      effective in improving self-care and quality of life as well as reducing
      rehospitalization rates. However, limited studies explored its effects in adult
      patients with SLE. Therefore, we performed a study to examine the effects of
      transitional care on self-care, readmission rates, and quality of life in adult
      patients with SLE. METHODS: This study was a single-center, single-blind, and
      parallel-group randomized controlled trial comparing transitional care with usual
      care in SLE patients from a university hospital in China. Evaluations were
      conducted at baseline before discharge and at 3 months after discharge by using
      hospital readmission rate, the Exercise of Self-Care Agency Scale, and the
      Medical Outcomes Study Short Form 36-item Health Survey for self-care and quality
      of life. Data were collected between June and December 2016. RESULTS: Compared
      with the usual care group, the transitional care group reported significantly
      greater improvement in self-care and quality of life. Additionally, the 30-day
      readmission rate for the patients in the transitional care group was
      significantly lower than in the usual care group, and this effect remained
      significant at 60 and 90 days after patient discharge. CONCLUSION: This study
      shows that transitional care improves self-care and quality of life in adult
      patients with SLE and reduces readmissions. However, further studies are needed.
      TRIAL REGISTRATION: China clinical trial registry, ChiCTR-IPR-16007708 .
      Registered January 5, 2016.

PMID- 30115111
TI  - Castleman disease versus lymphoma in neck lymph nodes: a comparative study using
      contrast-enhanced CT.
AB  - BACKGROUND: The purpose of this study was to determine the contrast-enhanced CT
      characteristics for differentiating between Castleman disease (CD) and lymphoma
      in neck lymph nodes. METHODS: This retrospective study evaluated the number
      (solitary or multiple), strength of contrast-enhancement, type of contrast
      enhancement, surrounding vessels, contrast-enhanced Hounsfield unit (HU) values,
      and anatomical distributions of lymph nodes in 34 patients with confirmed CD and
      55 patients with newly diagnosed untreated lymphoma. Independent t-tests,
      receiver operating characteristic (ROC) curve analysis, and chi-square tests were
      used to evaluate the variables and CT features. RESULTS: Several significant
      differences were found between CD and lymphoma. The interval between first
      contrast-enhanced CT and biopsy/surgery was significantly longer in the CD group
      (mean 72 +/- 105 days, median 60 days) than in the lymphoma patients (mean 30 +/-
      2 days, median 12 days; p = 0.015). The lymphoma patients presented significantly
      more often with fatigue and fever (p = 0.023 and p = 0.016 respectively) than did
      the CD subjects. HU values of nodules after enhancement were significantly higher
      in the CD patients than in the lymphoma patients. In cases involving multiple
      lymph nodes, in all the CD cases, all affected nodes were located in only the
      left or right side of the neck, not bilaterally. ROC analysis showed a
      significant difference in contrast-enhanced CT attenuation values between
      lymphoma and CD (p < 0.001, area under the curve = 0.954), with a cut-off value
      of 92.5 HU. We constructed a decision tree according to these imaging
      characteristics. CONCLUSIONS: Contrast-enhanced CT can be useful for
      differentiating between CD and lymphoma.

PMID- 30115112
TI  - Metacognitive therapy home-based self-help for cardiac rehabilitation patients
      experiencing anxiety and depressive symptoms: study protocol for a feasibility
      randomised controlled trial (PATHWAY Home-MCT).
AB  - BACKGROUND: Anxiety and depression are common among patients attending cardiac
      rehabilitation services. Currently available pharmacological and psychological
      interventions have limited effectiveness in this population. There are presently
      no psychological interventions for anxiety and depression integrated into cardiac
      rehabilitation services despite emphasis in key UK National Health Service
      policy. A new treatment, metacognitive therapy, is highly effective at reducing
      anxiety and depression in mental health settings. The principal aims of the
      current study are (1) to evaluate the acceptability of delivering metacognitive
      therapy in a home-based self-help format (Home-MCT) to cardiac rehabilitation
      patients experiencing anxiety and depressive symptoms and conduct a feasibility
      trial of Home-MCT plus usual cardiac rehabilitation compared to usual cardiac
      rehabilitation; and (2) to inform the design and sample size for a full-scale
      trial. METHODS: The PATHWAY Home-MCT trial is a single-blind feasibility
      randomised controlled trial comparing usual cardiac rehabilitation (control)
      versus usual cardiac rehabilitation plus home-based self-help metacognitive
      therapy (intervention). Economic and qualitative evaluations will be embedded
      within the trial. Participants will be assessed at baseline and followed-up at 4
      and 12 months. Patients who have been referred to cardiac rehabilitation
      programmes and have a score of >= 8 on the anxiety and/or depression subscales of
      the Hospital Anxiety and Depression Scale will be invited to take part in the
      study and written informed consent will be obtained. Participants will be
      recruited from the National Health Service in the UK. A minimum of 108
      participants will be randomised to the intervention and control arms in a 1:1
      ratio. DISCUSSION: The Home-MCT feasibility randomised controlled trial will
      provide evidence on the acceptability of delivering metacognitive therapy in a
      home-based self-help format for cardiac rehabilitation patients experiencing
      symptoms of anxiety and/or depression and on the feasibility and design of a full
      scale trial. In addition, it will provide provisional point estimates, with
      appropriately wide measures of uncertainty, relating to the effectiveness and
      cost-effectiveness of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov,
      NCT03129282 , Submitted to Registry: 11 April 2017.

PMID- 30115113
TI  - Comparison of crystalloid resuscitation fluids for treatment of acute brain
      injury: a clinical and pre-clinical systematic review and network meta-analysis
      protocol.
AB  - BACKGROUND: Current guidelines identify the choice of fluid resuscitation as
      important in minimizing the incidence of secondary brain injury from cerebral
      edema. It is widely accepted that isotonic crystalloid resuscitation fluids,
      specifically normal saline (NS), are optimal for resuscitation and that other
      relatively hypotonic fluids, such as Ringer's lactate (RL), should be avoided in
      this patient population. The aim of this review is to systematically compare the
      use of relatively hypotonic versus isotonic crystalloid resuscitation fluids in
      clinical and pre-clinical models of acute brain injury and their effect on
      outcomes. In recognition of the potential need for a network meta-analysis (NMA),
      we have also included all other relevant crystalloid resuscitation fluids as
      interventions of relevance to potentially inform indirect comparisons. METHODS:
      Systematic searches of MEDLINE, Embase, and Web of Science BIOSIS Previews(r)
      will be used to identify eligible clinical and pre-clinical studies, which
      included studies examining acute brain injury (human and in vivo animal brain
      injury models) within the first 7 days of therapy. The intervention of interest
      is the intravenous use of relatively hypotonic crystalloid resuscitation fluids
      (e.g., Ringer's lactate, Hartmann's or Plasma Lyte(r) fluids). The main
      comparator of interest is an isotonic crystalloid resuscitation fluid,
      specifically normal saline (0.9%). Other crystalloid resuscitation fluids (e.g.,
      hypertonic saline (3-23.4%)) will also be included as an additional intervention
      of interest. The primary outcome measures of interest are intracranial pressure
      (ICP) and cerebral perfusion pressure (CPP). Secondary outcomes include the
      effect of resuscitation on cerebral edema, brain and serum osmolarity, and
      electrolyte concentrations and clinical outcomes including modified Rankin Scale
      (mRS), (extended) Glasgow Outcome Scale (GOS/eGOS), and mortality. Separate meta
      analyses will be conducted to quantify the effects of the different fluid
      resuscitation on acute brain injury outcomes in clinical and pre-clinical
      populations. Network meta-analyses to compare interventions will also be
      performed to compare the effects of different interventions. DISCUSSION: This
      systematic review will comprehensively summarize the difference in treatment
      efficacy of various crystalloid resuscitation fluids in acute brain injury. This
      review is essential to underscore the evidence, or lack thereof, present in the
      literature to date to support current preference-driven practice and to direct
      future study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO #CRD42016042960.

PMID- 30115114
TI  - Mother's Infant and Young Child Feeding (IYCF) knowledge improved timely
      initiation of complementary feeding of children aged 6-24 months in the rural
      population of northwest Ethiopia.
AB  - OBJECTIVES: Appropriate complementary feeding is vital to reduce young child
      morbidity and mortality. However, it continues as sub-optimal in Ethiopia, and
      literatures are also scarce. Therefore, this study aimed to determine timely
      initiation of complementary feeding and associated factors among mothers with
      children aged 6-24 months in the rural population of northwest Ethiopia. In the
      community based cross-sectional study, data on child feeding practices,
      individual and household characteristics were collected in Dabat Demographic
      Surveillance System site, Dabat District, northwest Ethiopia from 01 May to 29
      June 2015. The bivariate and backward stepwise multivariable statistical methods
      were carried out to identify factors associated with timely initiation of
      complementary feeding. RESULTS: About 53.8% [95% CI 45.9, 61.7] and 4.6% [95% CI
      1.3, 7.9] of children were found with timely initiation of complementary feeding
      and had minimum dietary diversity, respectively. The odds of timely initiation of
      complementary feeding was higher among mothers with medium [AOR = 2.34, 95% CI
      1.54, 3.81] and high [AOR = 2.10, 95% CI 1.41, 3.87] mother's IYCF knowledge. In
      Dabat district, complementary feeding practice is lower. Thus, efforts should be
      strengthened to boost mother's IYCF knowledge.

PMID- 30115115
TI  - The potential of computerised analysis of bowel sounds for diagnosis of
      gastrointestinal conditions: a systematic review.
AB  - BACKGROUND: Gastrointestinal (GI) conditions are highly prevalent, and their
      standard diagnostic tests are costly and carry risks. There is a need for new,
      cost-effective, non-invasive tests. Our main objective was to assess the
      potential for use of bowel sounds computerised analysis in the diagnosis of GI
      conditions. METHODS: The systematic review followed the PRISMA requirements.
      Searches were made of four databases (PubMed, MEDLINE, Embase, and IEEE Xplore)
      and the references of included papers. Studies of all types were included. The
      titles and abstracts were screened by one author. Full articles were reviewed and
      data collected by two authors independently. A third reviewer decided on
      inclusion in the event of disagreement. Bias and applicability were assessed via
      a QUADAS tool adapted to accommodate studies of multiple types. RESULTS: Two
      thousand eight hundred eighty-four studies were retrieved; however, only 14
      studies were included. Most of these simply assessed associations between a bowel
      sound feature and a condition. Four studies also included assessments of
      diagnostic accuracy. We found many significant associations between a bowel sound
      feature and a GI condition. Receiver operating characteristic curve analyses
      revealed high sensitivity and specificity for an irritable bowel syndrome test,
      and a high negative predictive value for a test for post-operative ileus.
      Assessment of methodological quality identified weaknesses in all studies. We
      particularly noted a high risk of bias in patient selection. Because of the
      limited number of trials included and the variety in conditions, technology, and
      statistics, we were unable to conduct pooled analyses. CONCLUSIONS: Due to
      concerns over quality and small sample sizes, we cannot yet recommend an existing
      BSCA diagnostic test without additional studies. However, the preliminary results
      found in the included studies and the technological advances described in
      excluded studies indicate excellent future potential. Research combining
      sophistical clinical and engineering skills is likely to be fruitful. SYSTEMATIC
      REVIEW REGISTRATION: The review protocol (review ID number 42016054028) was
      developed by three authors (AI, KMW, and JM) and was published in the PROSPERO
      International prospective register of systematic reviews. It can be accessed from
      https://www.crd.york.ac.uk/PROSPERO/ .

PMID- 30115116
TI  - Dedifferentiated parosteal osteosarcoma of the maxilla: a case report and review
      of the literature.
AB  - BACKGROUND: Parosteal osteosarcomas are usually low-grade tumors, however,
      sometimes they transform to high-grade tumors, which is named dedifferentiation.
      This phenomenon has been reported in long bones. Recently, we encountered a
      patient with dedifferentiated parosteal osteosarcoma occurring in the maxilla.
      Here, we report a first case of dedifferentiated parosteal osteosarcoma of the
      head and neck region. CASE PRESENTATION: A 45-year-old Japanese woman with a
      refractory bone lesion in the maxilla presented to our hospital. A biopsy showed
      atypical spindle cell proliferation involving dedifferentiated high-grade
      component, which was diagnosed as dedifferentiated parosteal osteosarcoma. Three
      cycles of neoadjuvant chemotherapy using ifosfamide and pirarubicin were
      performed followed by sub-total maxillectomy. Histopathological results showed
      that neoadjuvant chemotherapy was effective for high-grade component. The
      decision to perform adjuvant chemotherapy (cisplatin and pirarubicin) was made
      because distant metastasis has been reported, even in cases with dedifferentiated
      parosteal osteosarcoma in which complete necrosis of high-grade component was
      achieved due to neoadjuvant chemotherapy. There was no recurrence 15 months after
      surgery. CONCLUSIONS: Dedifferentiated parosteal osteosarcoma can occur in the
      head and neck region. Chemotherapy including anthracycline anticancer agent could
      be effective for high-grade component of dedifferentiated parosteal osteosarcoma.

PMID- 30115118
TI  - Cerebrospinal fluid synaptosomal-associated protein 25 is a key player in
      synaptic degeneration in mild cognitive impairment and Alzheimer's disease.
AB  - BACKGROUND: There is accumulating evidence that synaptic loss precedes neuronal
      loss and correlates best with impaired memory formation in Alzheimer's disease
      (AD). Cerebrospinal fluid (CSF) synaptosomal-associated protein 25 (SNAP-25) is a
      newly discovered marker indicating synaptic damage. We here test CSF SNAP-25 and
      SNAP-25/amyloid-beta42 (Abeta42) ratio as a diagnostic marker for predicting
      cognitive decline and brain structural change in the Alzheimer's Disease
      Neuroimaging Initiative (ADNI) database. METHODS: We stratified 139 participants
      from the ADNI database into cognitively normal (CN; n = 52), stable mild
      cognitive impairment (sMCI; n = 22), progressive MCI (pMCI; n = 47), and dementia
      due to AD (n = 18). Spearman correlation was performed to test the relationships
      between biomarkers. Overall diagnostic accuracy (area under the curve (AUC)) was
      obtained from receiver operating curve (ROC) analyses. Cox proportional hazard
      models tested the effect of CSF SNAP-25 and SNAP-25/Abeta42 measures on the
      conversion from MCI to AD. Relationships between the CSF SNAP-25 levels, SNAP
      25/Abeta42 ratio, and diagnostic groups were tested with linear regressions.
      Linear mixed-effects models and linear regression models were used to evaluate
      CSF SNAP-25 and SNAP-25/Abeta42 as predictors of AD features, including cognition
      measured by the Mini-Mental State Examination (MMSE) and brain structure and
      white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI).
      RESULTS: CSF SNAP-25 and SNAP-25/Abeta42 were increased in patients with pMCI and
      AD compared with CN, and in pMCI and AD compared with sMCI. Cognitively normal
      subjects who progressed to MCI or AD during follow-up had increased SNAP
      25/Abeta42 ratio compared with nonprogressors. CSF SNAP-25, especially SNAP
      25/Abeta42, offers diagnostic utility for pMCI and AD. CSF SNAP-25 and SNAP
      25/Abeta42 significantly predicted conversion from MCI to AD. In addition,
      elevated SNAP-25/Abeta42 ratio was associated with the rate of hippocampal
      atrophy in pMCI and the rate of change of cognitive impairment in CN over the
      follow-up period. CONCLUSIONS: These data suggest that both CSF SNAP-25 and SNAP
      25/Abeta42 ratio are already increased at the early clinical stage of AD, and
      indicate the promise of CSF SNAP-25 and SNAP-25/Abeta42 ratio as diagnostic and
      prognostic biomarkers for the earliest symptomatic stage of AD.

PMID- 30115117
TI  - IgM response against amyloid-beta in aging: a potential peripheral protective
      mechanism.
AB  - BACKGROUND: The immune system plays a major role in the pathogenesis of age
      related dementia, including Alzheimer's disease (AD). An insight into age
      associated changes in the immune response to amyloid-beta (Abeta) in individuals
      without AD may be beneficial in identifying mechanisms preventing accumulation of
      Abeta. METHODS: We examined the response of human monocyte-derived dendritic
      cells (DCs), T cells, and peripheral blood mononuclear cells (PBMCs) from healthy
      aged and young subjects to Abeta peptide 1-42, Abeta fibrils, and recombinant,
      nonaggregated tau-4 protein with a view to understand the role of peripheral
      immunity in AD. RESULTS: Our studies revealed that DCs from healthy aged subjects
      display weak reactivity towards the Abeta peptide and no reactivity towards Abeta
      fibrils and tau compared with their young counterparts. An analysis of old and
      young PBMCs revealed that there is no significant T-cell memory against Abeta
      peptide, fibrils, or tau. Remarkably, the plasma levels of IgM antibodies
      specific to Abeta peptide 1-42 were significantly increased in aged subjects
      compared with young subjects, while IgG levels were comparable. Abeta peptide
      specific IgM and IgG levels were also determined in the plasma of AD subjects
      compared with age-matched controls to demonstrate that the immune response
      against Abeta is stronger in AD patients. A decline in Abeta peptide-specific IgM
      antibodies was observed in AD patients compared with age-matched controls. In
      contrast, the levels of IgG as well as interleukin-21, the major cytokine
      involved in class switching, were increased in AD and patients with mild
      cognitive impairment, indicating a strong immune response against Abeta.
      CONCLUSIONS: Collectively, low immunogenicity of Abeta in healthy controls may
      prevent inflammation while the generation of specific IgM antibodies may help in
      the clearance of Abeta in healthy subjects.

PMID- 30115119
TI  - Evaluation of 99mTc-rhAnnexin V-128 SPECT/CT as a diagnostic tool for early
      stages of interstitial lung disease associated with systemic sclerosis.
AB  - BACKGROUND: Given the need for early detection of organ involvement in systemic
      sclerosis, we evaluated 99mTc-rhAnnexin V-128 for the detection of early stages
      of interstitial lung disease (ILD) in respective animal models using single
      photon emission computed tomography (SPECT/CT). METHODS: In bleomycin (BLM)
      challenged mice, fos-related antigen 2 (Fra-2) transgenic (tg) mice and
      respective controls, lung injury was evaluated by analysis of hematoxylin and
      eosin (HE) and Sirius red staining, with semi-quantification of fibrosis by the
      Ashcroft score. Apoptotic cells were identified by TUNEL assay, cleaved caspase 3
      staining and double staining with specific cell markers. To detect early stages
      of lung remodeling by visualization of apoptosis, mice were injected
      intravenously with 99mTc-rhAnnexin V-128 and imaged by small animal SPECT/CT. For
      confirmation, biodistribution and ex vivo autoradiography studies were performed.
      RESULTS: In BLM-induced lung fibrosis, inflammatory infiltrates occurred as early
      as day 3 with peak at day 7, whereas pulmonary fibrosis developed from day 7 and
      was most pronounced at day 21. In accordance, the number of apoptotic cells was
      highest at day 3 compared with saline controls and then decreased over time.
      Epithelial cells (E-cadherin+) and inflammatory cells (CD45+) were the primary
      cells undergoing apoptosis in the earliest remodeling stages of experimental ILD.
      This was also true in the pathophysiologically different Fra-2 tg mice, where
      apoptosis of CD45+ cells occurred in the inflammatory stage. In accordance with
      the findings on tissue level, at day 3 in the BLM and at week 16 in the Fra-2 tg
      model, biodistribution and/or ex vivo autoradiography showed increased pulmonary
      uptake of 99mTc-rhAnnexin V-128 compared with controls. However, accumulation of
      the radiotracer and thus the signal intensity in lungs was too low to allow the
      differentiation of healthy and injured lungs in vivo. CONCLUSION: At the tissue
      level, 99mTc-rhAnnexin V-128 successfully demonstrated early stages of ILD in two
      animal models by detection of apoptotic epithelial and/or inflammatory cells. In
      vivo, however, we did not detect early lung injury. It remains to be investigated
      whether the same applies to human ILD.

PMID- 30115120
TI  - Aberrantly expressed messenger RNAs and long noncoding RNAs in degenerative
      nucleus pulposus cells co-cultured with adipose-derived mesenchymal stem cells.
AB  - BACKGROUND: Stem cell therapy is considered as a promising alternative to treat
      intervertebral disc degeneration (IDD). Extensive work had been done on
      identifying and comparing different types of candidate stem cells, both in vivo
      and in vitro. However, few studies have shed light on degenerative nucleus
      pulposus cells (NPCs), especially their biological behavior under the influence
      of exogenous stem cells, specifically the gene expression and regulation pattern.
      In the present study, we aimed to determine messenger RNAs (mRNAs) and long non
      coding RNAs (lncRNAs), which are differentially expressed during the co-culturing
      process with adipose-derived mesenchymal stem cells (ASCs) and to explore the
      involved signaling pathways and the regulatory networks. METHODS: We compared
      degenerative NPCs co-cultured with ASCs with those cultured solely using lncRNA
      mRNA microarray analysis. Based on these data, we investigated the significantly
      regulated signaling pathways based on the Kyoto Encyclopedia of Genes and Genomes
      (KEGG) pathway database. Moreover, 23 micro RNAs (miRNAs), which were
      demonstrated to be involved in IDD were chosen; we investigated their theoretic
      regulatory importance associated with our microarray data. RESULTS: We found 632
      lncRNAs and 1682 mRNAs were differentially expressed out of a total of 40,716
      probes. We then confirmed the microarray data by real-time PCR. Furthermore, we
      demonstrated 197 upregulated, and 373 downregulated Gene Ontology terms and 176
      significantly enriched pathways, such as the mitogen-activated protein kinase
      (MAPK) pathway. Also, a signal-net was constructed to reveal the interplay among
      differentially expressed genes. Meanwhile, a mRNA-lncRNA co-expression network
      was constructed for the significantly changed mRNAs and lncRNAs. Also, the
      competing endogenous RNA (ceRNA) network was built. CONCLUSION: Our results
      present the first comprehensive identification of differentially expressed
      lncRNAs and mRNAs of degenerative NPCs, altered by co-culturing with ASCs, and
      outline the gene expression regulation pattern. These may provide valuable
      information for better understanding of stem cell therapy and potential candidate
      biomarkers for IDD treatment.

PMID- 30115121
TI  - Topiramate versus naltrexone for alcohol use disorder: study protocol for a
      genotype-stratified, double-blind randomised controlled trial (TOP study).
AB  - BACKGROUND: Current treatments for alcohol use disorders have limited efficacy
      and there is a high degree of variability in treatment response. In a randomised,
      placebo-controlled clinical trial, there was a large effect size for topiramate
      in people homozygous for the GRIK1 rs2832407*C allele. The primary aim of the TOP
      study is to examine prospectively the therapeutic and cost-effectiveness of
      topiramate versus an active control (naltrexone) in improving treatment outcomes
      for alcohol dependence. Participants will be stratified on rs2832407 to compare C
      allele homozygotes with A-allele carriers to examine the moderating effect of
      rs2832407 on drinking outcomes. An exploratory aim is to examine the moderating
      effects of rs1799971, a polymorphism in OPRM1, on the response to naltrexone by
      comparing Asn40 homozygotes with Asp40 carriers. METHODS/DESIGN: This double
      blind trial will randomise 180 alcohol-dependent participants to a 12-week regime
      of either topiramate (titrating the dose up to 200 mg/day) or naltrexone (50
      mg/day). Participants will be stratified on the two polymorphisms before
      randomisation. All participants will receive medical management. The primary
      drinking outcome will be the number of heavy drinking days per week and secondary
      drinking outcomes will include the time to relapse, the time to lapse and the
      percentage of abstinent days. Other secondary outcomes will include body mass
      index, tobacco use, anxiety symptoms and depressive symptoms. DISCUSSION: If
      successful, the TOP study will improve management strategies for alcohol
      dependence by providing support for the use of genetic biomarkers to inform
      medication selection. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03479086 .
      Registered on 27 March 2018.

PMID- 30115122
TI  - The wild side of plant microbiomes.

PMID- 30115123
TI  - Correction to: Antihypertensive medication adherence and associated factors among
      adult hypertensive patients at Jimma University Specialized Hospital, southwest
      Ethiopia.
AB  - After publication of our article [1] we became aware that we had not obtained
      permission to reproduce the questions from the eight-item Morisky's Medication
      Adherence Scale. The table in this Correction replaces Table 2 in our article. In
      addition, the second number for the MMAS-8 question 2 was incorrect and has been
      updated to 223(79.6).

PMID- 30115124
TI  - Adding body load modifies the vibratory sensation of the foot sole and affects
      the postural control.
AB  - BACKGROUND: Heavy backpacks are often used by soldiers and firefighters. Weight
      carrying could reduce the speed and efficiency in task completion by altering the
      foot sole sensitivity and postural control. METHODS: In fifteen healthy subjects,
      we measured the changes in sensitivity to vibrations applied to the foot sole
      when standing upright or walking after load carrying (30% body weight). The
      participants were asked to judge different vibration amplitudes applied on the
      2nd or 5th metatarsal head and the heel at two frequencies (25 and 150 Hz) to
      determine the vibration threshold and the global perceptual representation (?)of
      the vibration amplitude (F) given by the Stevens power function (? = k * Fn). Any
      increase in negative k value indicated a reduction in sensitivity to the lowest
      loads. Pedobarographic measurements, with computation of the center of pressure
      (COP) and its deviations, were performed during weight carrying. RESULTS: The 25
      Hz vibration threshold significantly increased after weight carrying when
      standing upright or walking. After standing with the added loads, the absolute
      negative k value increased for the 25 Hz frequency. After walking with the added
      loads, the k coefficient increased for the two vibration frequencies. Weight
      carrying significantly increased both the CoP surface and CoP lateral deviation.
      CONCLUSIONS: Our data show that weight carrying reduces the sensory pathways from
      the foot sole and accentuates the center of pressure deviations.

PMID- 30115125
TI  - Identification of target genes in cardiomyopathy with fibrosis and cardiac
      remodeling.
AB  - BACKGROUND: Identify genes probably associated with chronic heart failure and
      predict potential target genes for dilated cardiomyopathy using bioinformatics
      analyses. METHODS: Gene expression profiles (series number GSE3585 and GSE42955)
      of cardiomyopathy patients and healthy controls were downloaded from the
      Expression Omnibus Gene (GEO) database. Differential expression of genes (DEGS)
      between the two groups of total 14 cardiomyopathy patients and 10 healthy
      controls were subsequently identified by limma package of R. Database for
      Annotation, Visualization, and Integrated Discovery (DAVID Tool), which is an
      analysis of enriched biological processes. Search Tool for the Retrieval
      Interacting Genes (STRING) was used as well for the analysis of protein-protein
      interaction network (PPI). Prediction of the potential drugs was suggested based
      on the preliminarily identified genes using Connectivity Map (CMap). RESULTS:
      Eighty-nine DEGs were identified (57 up-regulated and 32 down-regulated). The
      most enrichment Gene Ontology (GO) terms (P < 0.05) contain genes involved in
      extracellular matrix (ECM) and biological adhesion signal pathways (P < 0.05, ES
      > 1.5) such as ECM-receptors, focal adhesion and transforming growth factor beta
      (TGF-beta), etc. Fifty-one differentially expressed genes were found to encode
      interacting proteins. Eleven key genes along with related transcription factors
      were identified including CTGF, POSTN, CORIN, FIGF, etc. CONCLUSION:
      Bioinformatics-based analyses reveal the targeted genes probably associated with
      cardiomyopathy, which provide clues for pharmacological therapies aiming at the
      targets.

PMID- 30115126
TI  - Does mandatory reporting legislation increase contact with child protection? - a
      legal doctrinal review and an analytical examination.
AB  - BACKGROUND: Within Canadian provinces over the past half-century, legislation has
      been enacted to increase child protection organization (CPO) involvement in
      situations of child maltreatment (CM). This study had two objectives: 1) to
      document enactment dates of legislation for mandatory reporting of CM; 2) to
      examine reported CPO involvement among people reporting a CM history in relation
      to the timing of these legislative changes. METHODS: The history of mandatory
      reporting of CM was compiled using secondary sources and doctrinal legal review
      of provincial legislation. The 2012 Canadian Community Health Survey - Mental
      Health (CCHS-MH) with n = 18,561 was analyzed using birth cohorts to assess
      associations between the timing of legislation enactment and contact with CPO.
      RESULTS: All Canadian provinces currently have mandatory reporting of physical
      and sexual abuse; 8 out of 10 provinces have mandatory reporting for children's
      exposure to intimate partner violence. Increases in reporting CM to CPOs
      paralleled these laws' enactment, particularly for severe and frequent CM.
      CONCLUSIONS: These findings show that mandatory reporting laws increase reporting
      contact with CPO, particularly for severe and frequent CM. Whether they have had
      the intended effect of improving children's lives remains an important,
      unanswered question.

PMID- 30115129
TI  - ETV6/RUNX1-positive childhood acute lymphoblastic leukemia in China: excellent
      prognosis with improved BFM protocol.
AB  - BACKGROUND: In childhood B-precursor acute lymphoblastic leukemia (B-ALL), the
      ETV6/RUNX1 fusion transcript is considered to have an excellent outcome. However,
      few studies of children with ETV6/RUNX1-positive ALL from China have been
      conducted. It is largely unknown whether clinical outcomes for patients with this
      genotype and important factors that influence such outcomes are similar to those
      reported in other countries. Therefore, it is important to analyze the outcomes
      of children with ETV6/RUNX1-positive ALL treated at our institution with the aim
      of identifying significant prognostic variables in a Chinese population. METHODS:
      We studied the clinical characteristics and treatment outcomes for 77 pediatric
      patients diagnosed with ETV6/RUNX1-positive ALL between 2005 and 2015 at our
      institution. RESULTS: The 5-year event-free survival (EFS) and the disease-free
      survival (DFS) were reported to be 90% +/- 3% and 96% +/- 3% respectively. Two
      patients had a relapse at a median of 42 months from diagnosis and the 5-year
      cumulative incidence of relapse was 2.1%. Despite intensive chemotherapy or
      allogeneic hematopoietic cell transplantation, the 2 relapsed patients succumbed
      to the disease progression and the 5-year overall survival (OS) was 97% +/- 2%.
      Multivariate analysis for EFS revealed that the minimal residual disease (MRD)
      >=10- 3 on Day + 33 negatively affected the outcome. CONCLUSIONS: In conclusion,
      patients with ETV6/RUNX1 fusion transcript can achieve a high rate of complete
      remission and the long-term curative effect was excellent under risk-stratified
      treatment. In case of relapse, the MRD level at the end of induction therapy
      should be taken into consideration while deciding the appropriate chemotherapy
      dosage.

PMID- 30115130
TI  - Association of osteoarthritis and circulating adiponectin levels: a systematic
      review and meta-analysis.
AB  - BACKGROUND: The objective of this study was to perform a meta-analysis to
      investigate the specific relationship between the expression level of circulating
      adiponectin and osteoarthritis (OA). METHOD: Multiple databases were searched to
      estimate the high quality of studies relevant to adiponectin and OA. We extracted
      the data from the eligible studies and included them in the meta-analysis using a
      random effects model. Subgroup analysis and meta-regression were further
      performed to explore the potential sources of heterogeneity. RESULTS: Ten
      articles consisting of thirteen case-control studies that contained a combined
      total of 1255 subjects. Our results revealed that the OA patients displayed
      higher adiponectin levels than the healthy controls (SMD = 0.327, 95% CI: 0.11
      0.55, P = 0.003). The ethnicity-stratified subgroup analysis indicated that the
      adiponectin was a sensitive biomarker in both Caucasians (P = 0.021) and Asians
      (P = 0.037). Moreover, the meta-regression analysis suggested that the sample
      size (P = 0.03) and nationality (p = 0.01) could account for a part of
      heterogeneity in our study. CONCLUSION: Taken together, the current study
      indicated that the adiponectin expression levels were higher in the OA patients
      than in the healthy controls and might be associated with OA prevalence.

PMID- 30115128
TI  - Optical and physical mapping with local finishing enables megabase-scale
      resolution of agronomically important regions in the wheat genome.
AB  - BACKGROUND: Numerous scaffold-level sequences for wheat are now being released
      and, in this context, we report on a strategy for improving the overall assembly
      to a level comparable to that of the human genome. RESULTS: Using chromosome 7A
      of wheat as a model, sequence-finished megabase-scale sections of this chromosome
      were established by combining a new independent assembly using a bacterial
      artificial chromosome (BAC)-based physical map, BAC pool paired-end sequencing,
      chromosome-arm-specific mate-pair sequencing and Bionano optical mapping with the
      International Wheat Genome Sequencing Consortium RefSeq v1.0 sequence and its
      underlying raw data. The combined assembly results in 18 super-scaffolds across
      the chromosome. The value of finished genome regions is demonstrated for two
      approximately 2.5 Mb regions associated with yield and the grain quality
      phenotype of fructan carbohydrate grain levels. In addition, the 50 Mb centromere
      region analysis incorporates cytological data highlighting the importance of non
      sequence data in the assembly of this complex genome region. CONCLUSIONS:
      Sufficient genome sequence information is shown to now be available for the wheat
      community to produce sequence-finished releases of each chromosome of the
      reference genome. The high-level completion identified that an array of seven
      fructosyl transferase genes underpins grain quality and that yield attributes are
      affected by five F-box-only-protein-ubiquitin ligase domain and four root
      specific lipid transfer domain genes. The completed sequence also includes the
      centromere.

PMID- 30115131
TI  - Dietary habits and metabolic risk factors for non-communicable diseases in a
      university undergraduate population.
AB  - BACKGROUND: Unhealthy dietary patterns are associated with metabolic changes and
      increased risk of non-communicable diseases (NCDs), but these associations have
      not been investigated in representative populations of university undergraduates
      in low-to-middle income countries (LMICs). METHODS: This study was conducted in
      the three universities in Lagos State, Nigeria to assess the dietary pattern and
      metabolic risk factors of NCDs among university undergraduate population.
      Multistage sampling technique was used to select 506 undergraduates from the
      universities. Pre-tested questionnaire was used to obtain data on socio
      demographic characteristics and dietary patterns. Body mass index and metabolic
      risk factors (abdominal obesity, dyslipidemias, high blood pressure and
      hyperglycemia) were assessed following standard procedures. SPSS (version 20) was
      used for data entry and analysis. Association between variables was determined
      using chi-square and Fisher's exact tests. RESULTS: The mean age was 20.3 +/- 3.5
      years; 54.7% of them were female. More than one third (37.6%) had no consistent
      source of income or received less than N10, 000 ($31.7) per month. Less than one
      third (31.0%) ate three daily meals, 23.0% ate breakfast regularly, and only 2%
      consumed the recommended daily amount of fruits and vegetables. Almost half
      (44.0%) ate pastry snacks daily. Refined rice was the commonest cereal (28.2%)
      consumed while meat was more commonly consumed daily (32.0%) than milk (14.0%)
      and fish (10.0%). Twenty-nine (29.0%) and 6.2% of the population daily consumed
      carbonated soft drinks and alcohol, respectively. Prevalence of abdominal obesity
      (based on waist circumference) was 5% (1.3% in males and 8.4% in females),
      dyslipidemias (57.3%), pre-hypertension (8.2%), hypertension (2.8%), and pre
      diabetes (1.0%). Obesity was positively associated with consumption of alcohol
      (chi2 = 13.299, p < 0.001). CONCLUSION: Unhealthy diets and metabolic risk
      factors of non-communicable diseases are prevalent in the undergraduate
      population studied. Well-recognized recommendations regarding adequate
      consumption of fruits, vegetables, fish, and whole grains should be emphasized in
      a targeted manner in this population. Carbonated soft drinks and alcohol
      consumption should be discouraged to stem a rising tide of metabolic risk factors
      for non-communicable diseases among undergraduate students.

PMID- 30115133
TI  - Could ultrasound-guided internal jugular vein catheter insertion replace the use
      of chest X-ray?

PMID- 30115134
TI  - Local perspectives and context in relation to feeding practices of children under
      2 years in the mountain villages of northern Thailand.
AB  - OBJECTIVE: To gain an in-depth understanding of infant and young child feeding
      practices, accompanying beliefs and their sociocultural context in the Karen and
      Lua ethnic communities of northern Thailand. DESIGN: A two-day workshop and
      thirty in-depth interviews were undertaken in June 2014. Dialogue occurred with
      the assistance of translators and was recorded, transcribed and translated. A
      detailed thematic analysis was undertaken. SETTING: Northern Thai indigenous
      communities in which one-third of the children under 5 years of age are stunted.
      SUBJECTS: People with various roles in the local health system and twenty-six
      villagers who cared for infants and young children. RESULTS: Predominant breast
      feeding was said to occur for 1 to 3 months but was not exclusive due to early
      introduction of water and/or rice. Exclusive breast-feeding for 6 months was
      impeded by the need for mothers to return to farming work, with the early
      introduction of solids enabling infants to be cared for by other family members.
      Low variety in complementary foods was typical during infancy, with few local
      foods having appropriate texture and special preparation of foods rarely
      described. A pervasive underlying issue is women's responsibility to labour and
      lack of time to care for their young children. Poverty and food insecurity also
      featured in participants' accounts. CONCLUSIONS: In combination, women's limited
      time to care, poverty and food insecurity are perpetuating poor nutrition of
      children in early life. Agricultural solutions that are being explored should
      also attend to the burden of work for women.

PMID- 30115132
TI  - Investigating the impact of poverty on colonization and infection with drug
      resistant organisms in humans: a systematic review.
AB  - BACKGROUND: Poverty increases the risk of contracting infectious diseases and
      therefore exposure to antibiotics. Yet there is lacking evidence on the
      relationship between income and non-income dimensions of poverty and
      antimicrobial resistance. Investigating such relationship would strengthen
      antimicrobial stewardship interventions. METHODS: A systematic review was
      conducted following Preferred Reporting Items for Systematic Reviews and Meta
      Analyses (PRISMA) guidelines. PubMed, Ovid, MEDLINE, EMBASE, Scopus, CINAHL,
      PsychINFO, EBSCO, HMIC, and Web of Science databases were searched in October
      2016. Prospective and retrospective studies reporting on income or non-income
      dimensions of poverty and their influence on colonisation or infection with
      antimicrobial-resistant organisms were retrieved. Study quality was assessed with
      the Integrated quality criteria for review of multiple study designs (ICROMS)
      tool. RESULTS: Nineteen articles were reviewed. Crowding and homelessness were
      associated with antimicrobial resistance in community and hospital patients. In
      high-income countries, low income was associated with Streptococcus pneumoniae
      and Acinetobacter baumannii resistance and a seven-fold higher infection rate. In
      low-income countries the findings on this relation were contradictory. Lack of
      education was linked to resistant S. pneumoniae and Escherichia coli. Two papers
      explored the relation between water and sanitation and antimicrobial resistance
      in low-income settings. CONCLUSIONS: Despite methodological limitations, the
      results suggest that addressing social determinants of poverty worldwide remains
      a crucial yet neglected step towards preventing antimicrobial resistance.

PMID- 30115135
TI  - Testing the Enemy Release Hypothesis on tall-statured grasses in South Africa,
      using Arundo donax, Phragmites australis, and Phragmites mauritianus as models.
AB  - The Enemy Release Hypothesis (ERH) predicts that introduced plant species can
      escape herbivory and therefore have a competitive advantage over native plants,
      which are exposed to both generalist and specialist natural enemies. In this
      study, the ERH was explored using the invasive alien species, Arundo donax and
      two native tall-statured grasses, the cosmopolitan Phragmites australis and
      African endemic Phragmites mauritianus in South Africa. It was predicted that A.
      donax would have reduced species richness of herbivores compared with the native
      Phragmites spp., that it would be devoid of specialist herbivores and would thus
      be experiencing enemy escape in the adventive range. The herbivore assemblages
      were determined from both field surveys and a literature review. The assumptions
      of the ERH were for the most part not met; 13 herbivores were found on A. donax
      compared with 17 on P. australis and 20 on P. mauritianus. Arundo donax had two
      specialist herbivores from its native range, and shared native herbivores with
      Phragmites spp. Although A. donax had reduced species richness and diversity
      compared with that found in the native distribution, it has partially re-acquired
      a herbivore assemblage which is similar to that found on analogous native
      species. This suggests that enemy release may not fully explain the invasive
      success of A. donax in South Africa.

PMID- 30115137
TI  - Delivering recovery focused mental health care in Ireland: implications for
      services and practice development.
AB  - : Introduction The recovery approach provides a key organising principle
      underlying mental health policy throughout the English speaking world with
      endorsement by agencies such as the World Health Organisation. In Ireland,
      personal recovery is one of the quality markers identified by users of mental
      health services and has become central to national mental health policy. Aim and
      objective The aim of this study was to explore the implications for mental health
      services and professional practice arising from a structured investigation of
      what personal recovery means for people using specialist mental health services
      and the extent to which services support their individual recovery. METHOD: Ten
      service user participants in a service initiative were assessed using a novel
      measure based on an empirically based conceptual framework of recovery. The
      INSPIRE determines the level of recovery promoting support received from mental
      health staff and the quality of the supportive relationship as perceived by
      individual service users. RESULTS: A consistent pattern of beliefs about recovery
      in keeping with national guidelines and the international literature was
      apparent. All respondents indicated that support by other people was an important
      part of their recovery with high levels of support received from mental health
      professionals. There was less consistent endorsement of the quality of
      relationships with professionals and recovery-oriented practice as perceived by
      participants. CONCLUSION: The findings are highly relevant to the development of
      recovery focused, clinically excellent services. Further work is needed to
      improve the process of translating recovery guidance into mental health practice.

PMID- 30115138
TI  - Irish General Practitioner referrals to psychological therapies.
AB  - OBJECTIVE: General Medical Practitioners play a crucial role in the detection and
      referral of mental health problems in primary care. This study describes the
      referral patterns of Irish General Practitioners (GPs) to psychological therapies
      and profiles the range of psychological therapies available. METHOD: A 21-item
      study-specific questionnaire exploring referral processes to psychological
      therapies was sent to all GPs listed by the Irish College of General
      Practitioners in one county in Ireland. A 19-item questionnaire exploring details
      of psychological therapies offered and referral pathways was sent to members of
      psychological therapy accrediting bodies in the same county. RESULTS: Of 97 GP
      respondents (33% response rate), their estimation of the percentage of their
      patients who have presenting or underlying mental health issues averaged 22%.
      When asked to indicate which psychological therapies they consider for referrals,
      psychiatric referrals was the most frequent referral option (94%), followed by
      Counsellors (69%), Clinical psychologist (60%) and Psychotherapists (30%). GPs
      indicated they had some or very little knowledge of specific psychological
      therapies. Of 129 psychological therapists (45% response rate), self-referral and
      GP referral were their main referral pathways; 80% worked in private practice;
      highest qualification level was Undergraduate/Higher Diploma (66%), Master Level
      (39%) and Doctoral Level (5%). CONCLUSION: GPs refer patients presenting with
      mental health problems to psychiatrists with significantly lower percentages
      referring to other types of psychological therapists. Findings demonstrate that
      there is a need for greater education and information-sharing between GPs and
      providers of accredited psychological therapies to increase knowledge on specific
      therapies and their evidence base.

PMID- 30115136
TI  - Dietary protein and changes in markers of cardiometabolic health across 20 years
      of follow-up in middle-aged Americans.
AB  - OBJECTIVE: Dietary protein plays a role in counteracting age-related muscle loss.
      However, limited long-term data exist on protein intake and markers of
      cardiometabolic health, which tend to deteriorate with age. DESIGN: Prospective
      cohort study. FFQ-derived protein intake (g/d) and cardiometabolic markers were
      assessed up to five times across 20 years. Markers included systolic (SBP) and
      diastolic (DBP) blood pressures, circulating lipids (total, HDL and LDL
      cholesterol; TAG), estimated glomerular filtration rate (eGFR), fasting glucose
      (FG), weight and waist circumference (WC). Mixed models accounting for repeated
      measures were used to estimate adjusted mean annualized changes in outcomes per
      quartile category of protein. SETTING: Framingham Heart Study Offspring cohort,
      USA. SUBJECTS: Participants (n 3066) with 12 333 unique observations, baseline
      (mean (sd)) age=54.0 (9.7) years, BMI=27.4 (4.9) kg/m2, 53.5 % female. RESULTS:
      In fully adjusted models, there were favourable associations (mean (se)) of total
      protein with annualized changes in SBP (lowest v. highest intake: 0.34 (0.06) v.
      0.04 (0.06) mmHg, P trend=0.001) and eGFR (-1.03 (0.06) v. -0.87 (0.05) ml/min
      per 1.73 m2, P trend=0.046), unfavourable associations with changes in FG (0.013
      (0.004) v. 0.028 (0.004) mmol/l, P trend=0.004) and no associations with weight,
      WC, DBP or lipids. Animal protein was favourably associated with SBP and
      unfavourably with FG and WC; plant protein was favourably associated with FG and
      WC. CONCLUSIONS: The present study provides evidence that protein intake may
      influence changes in cardiometabolic health independent of change in weight in
      healthy adults and that protein's role in cardiometabolic health may depend on
      the protein source.

PMID- 30115139
TI  - Delirious mania intractable to treatment.
AB  - We present the case of a 68-year-old lady with a background diagnosis of bipolar
      disorder, who developed significant episodes of intractable delirium during each
      of her last three inpatient psychiatric admissions, where she was admitted with
      mania and psychosis. The case demonstrates diagnostic and management difficulties
      secondary to this delirium. We discuss the probable cause of this delirium and
      the various management strategies utilised in an effort to ameliorate her
      condition.

PMID- 30115140
TI  - Mental illness self-management: a randomised controlled trial of the Wellness
      Recovery Action Planning intervention for inpatients and outpatients with
      psychiatric illness.
AB  - OBJECTIVE: Wellness Recovery Action Planning (WRAP) is a cross-diagnostic,
      patient-centred, self-management intervention for psychiatric illness. WRAP
      utilises an individualised Wellness Toolbox, a six part structured monitoring and
      response system, and a crisis and post-crisis plan to promote recovery. The
      objective of this study was to evaluate the effect of WRAP on personal recovery,
      quality of life, and self-reported psychiatric symptoms. METHOD: A prospective
      randomised controlled trial, based on the CONSORT principles was conducted using
      a sample of 36 inpatients and outpatients with a diagnosis of a mental disorder.
      Participants were randomly allocated to Experimental Group or Waiting List
      Control Group conditions in a 1:1 ratio. Measures of personal recovery, personal
      recovery life areas, quality of life, anxiety, and depression were administered
      at three time points: (i) pre-intervention, (ii) post-Experimental Group
      intervention delivery, and (iii) 6-month follow-up. Data was analysed by
      available case analysis using univariate and bivariate methodologies. RESULTS:
      WRAP had a significant effect on two personal recovery life areas measured by the
      Mental Health Recovery Star: (i) addictive behaviour and (ii) identity and self
      esteem. WRAP did not have a significant effect on personal recovery (measured by
      the Mental Health Recovery Measure), quality of life, or psychiatric symptoms.
      CONCLUSIONS: Findings indicate that WRAP improves personal recovery in the areas
      of (i) addictive behaviour and (ii) identity and self-esteem. Further research is
      required to confirm WRAP efficacy in other outcome domains. Efforts to integrate
      WRAP into recovery-orientated mental health services should be encouraged and
      evaluated.

PMID- 30115141
TI  - Mental health outcomes at age 11 of very low birth weight infants in Ireland.
AB  - : Aim To compare mental health (MH) outcomes of and service use by children born
      under 1500 g in Ireland with a matched control group. METHOD: Using a
      retrospective cohort design, semi-structured and standardised MH assessments were
      conducted with parents, teachers and youth. RESULTS: A total of 64 of 127
      surviving children from a very low birth weight (VLBW) cohort from a National
      Maternity Hospital participated at a mean age of 11.6 years (s.d. 1.0), along
      with 51 matched controls. More VLBW children received clinical or borderline
      scores when rated by parents [chi 2 (1, n=114)=7.3, p=0.007] or youths [chi 2 (1,
      n=114)=4.83, p=0.028], but not by teachers [chi 2 (1, n=114)=1.243, p=0.463].
      There was no increase in the use of MH services. A main effect of birth weight
      remained on the parent Strengths and Difficulties Questionnaire [F (1, 88)=5.07,
      p<0.05) after controlling for intelligence quotient (IQ) and socio-economic
      status (SES), but only on hyperactivity in males. SES, rather than IQ or birth
      weight, predicted identification of problems by teachers [F (1, 82)=6.99,
      p=0.01). Interpretations Teachers miss MH difficulties and are influenced more by
      SES than by IQ or birth weight. This has implications for MH service access.
      Initial perinatal investment needs to be matched with ongoing surveillance and
      psychoeducation to ensure that disorders are recognised early and offered
      appropriate interventions.

PMID- 30115142
TI  - An exciting new chapter for the Irish Journal of Psychological Medicine.
AB  - It is with great optimism that I step into the role as Editor-in-Chief with Irish
      Journal of Psychological Medicine. Much progress has been made since inception of
      the journal over three decades ago, most recently marked by new partnerships with
      the College of Psychiatrists of Ireland and Cambridge University Press. This is a
      crucial time for the journal to sustain and build on progress made to date. The
      journal will continue with the previous tradition of publishing high-quality
      original research, and will disseminate this research to an audience with the aim
      of improving mental health for all. I would like to express a huge gratitude to
      the outgoing Editor from all involved in the journal for the steadfast work
      throughout his tenure, and I look forward with enthusiasm to taking further steps
      of progress in this role.

PMID- 30115143
TI  - Thirty years of referrals to a community mental health service.
AB  - OBJECTIVES: In recent decades mental health services have become increasingly
      community based and multidisciplinary. However, it is unclear if referrals have
      changed over this period. The aim of this study was to compare referrals to a
      community mental health service over a 30-year period. METHOD: New referrals to a
      community mental health service were randomly sampled from 4 time points over a
      30-year period, 1983, 1993, 2003 and 2013, using a mental health information
      system. Original referral letters were retrieved and anonymised. Referrals were
      compared with regard to referral sources, demographics, reason for referral,
      psychotherapy requests, urgency, risk concerns and subsequent hospital admission.
      RESULTS: There was a 20-fold increase in the number of new referrals between 1983
      and 2013. Over the 30 years there was a significant decrease in the proportion of
      referrals expressing concern about psychosis, but an increase in the proportion
      that were deemed urgent and which were concerned with suicidal risk. Referrals in
      2013 were longer and more likely to contain requests for psychotherapy.
      CONCLUSIONS: The work of community mental health teams is increasingly concerned
      with emotional crises. Although services are now more multidisciplinary, they
      have not been adequately resourced to meet these changing demands.

PMID- 30115144
TI  - Psychological distress and frailty transitions over time in community-dwelling
      older adults.
AB  - OBJECTIVES: Physical health and, in particular, frailty may be associated with
      psychological factors among older adults. We aimed to investigate the
      relationships between aspects of psychological distress and progression of
      frailty over time among older adults. METHODS: We used a longitudinal
      observational study design with 624 participants aged over 60 years (mean
      age=72.75, s.d.=7.21, 68% female) completing a baseline comprehensive
      biopsychosocial geriatric assessment, and 447 returning for a follow-up
      assessment 2 years later. Aspects of psychological distress, physical health, and
      frailty were analysed for the purposes of this study. We employed a series of
      logistic regression analyses to determine psychological predictors of changing
      states of aspects of frailty over time. RESULTS: With individual components of
      frailty, neuroticism and age predicted negative transitions of exhaustion and
      grip strength, respectively, whereas age alone was a predictor of transitions in
      overall frailty scores based on four components. CONCLUSION: We conclude that
      neuroticism and age may impact upon physical frailty and its progression over
      time in an ageing population. These findings may reflect the tendency for those
      with high levels of neuroticism to endorse negative symptoms, or alternatively,
      neuroticism may result in exhaustion via worry in an older population. Further
      research is required to further elucidate this relationship.

PMID- 30115145
TI  - A pilot study of performance among hospitalised elderly patients on a novel test
      of visuospatial cognition: the letter and shape drawing (LSD) test.
AB  - OBJECTIVES: Conventional bedside tests of visuospatial function such as the clock
      drawing (CDT) and intersecting pentagons tests (IPT) are subject to considerable
      inconsistency in their delivery and interpretation. We compared performance on a
      novel test - the letter and shape drawing (LSD) test - with these conventional
      tests in hospitalised elderly patients. METHODS: The LSD, IPT, CDT and the
      Montreal Cognitive Assessment (MoCA) were performed in 40 acute elderly medical
      inpatients at University Hospital Limerick The correlation between these tests
      was examined as well as the accuracy of the visuospatial tests to identify
      significant cognitive impairment on the MoCA. RESULTS: The patients (mean age
      81.0+/-7.71; 21 female) had a median MoCA score of 15.5 (range=1-29). There was a
      strong, positive correlation between the LSD and both the CDT (r=0.56) and IPT
      (r=0.71). The correlation between the LSD and MoCA (r=0.91) was greater than for
      the CDT and IPT (both 0.67). The LSD correlated highly with all MoCA domains
      (ranging from 0.54 to 0.86) and especially for the domains of orientation
      (r=0.86), attention (0.81) and visuospatial function (r=0.73). Two or more errors
      on the LSD identified 90% (26/29) of those patients with MoCA scores of ?20,
      which was substantially higher than for the CDT (59%) and IPT (55%). CONCLUSION:
      The LSD is a novel test of visuospatial function that is brief, readily
      administered and easily interpreted. Performance correlates strongly with other
      tests of visuospatial ability, with favourable ability to identify patients with
      significant impairment of general cognition.

PMID- 30115146
TI  - An evaluation of community-based cognitive stimulation therapy: a pilot study
      with an Irish population of people with dementia.
AB  - OBJECTIVES: Research shows that cognitive stimulation therapy (CST) improves
      cognitive function, quality of life, and well-being of people with mild-moderate
      dementia. Despite consistent evidence and recommendations, CST is not routinely
      available in Ireland post-diagnosis. The aim of the current research was to
      develop and evaluate community-based CST for people with mild-moderate dementia,
      run by the Alzheimer Society of Ireland across four pilot sites in Ireland.
      METHODS: Participants with mild-moderate dementia attended once weekly CST
      sessions for 14 weeks. Baseline and post-intervention assessments were completed
      by CST participants, carers, and CST facilitators. Primary outcomes of interest
      for CST participants included quality of life (Quality of Life in Alzheimer
      Disease Scale), cognitive function (Montreal Cognitive Assessment), and
      subjective cognitive function (Memory Awareness Rating Scale-Functioning
      Subscale). Secondary outcomes included well-being, cognitive ability,
      satisfaction with cognitive performance, and engagement and confidence of CST
      participants; well-being of carers; and job satisfaction of facilitators. Post
      intervention interviews supplemented quantitative analyses. RESULTS: In total, 20
      CST participants, 17 carers, and six CST facilitators completed evaluation
      assessments. Results showed that CST improved participants' satisfaction with
      cognitive performance (p=0.002), level of engagement (p=0.046), level of
      confidence (p=0.026). Improvements on subjective cognitive function just fell
      short of significance (p=0.055). Qualitative analysis of interview data
      identified consistent themes of cognitive and overall benefits of CST; and
      provided support for quantitative data. CONCLUSIONS: Community-based CST
      positively impacted the lives of people with dementia and their families. This
      study supports prior recommendations that CST should be made routinely available
      to people with mild-moderate dementia, particularly in light of the lack of post
      diagnostic interventions currently offered in Ireland.

PMID- 30115147
TI  - Suicide in Ireland in the 19th century.
AB  - : Introduction This paper is an attempt to determine the extent and
      characteristics of suicide in 19th-century Ireland and the proportion of these
      that occurred in asylums. METHODS: The procedures used in this presentation
      involve analysis of data from the 1841 and 1851 Censuses of Ireland and the
      Reports of the Registrar-General of Ireland from 1864 to 1899 and the Annual
      Reports of the Inspectors of Lunacy, 1850 to 1899. RESULTS: Reported suicides had
      relatively low rates in the 19th century, ranging from 0.9 to 3.3 per 100 000 per
      year. The proportion of these suicides that occurred in asylums was low at ~4%.
      CONCLUSIONS: The reporting of suicide as a cause of death was relatively rare in
      the first-half of the 19th century in Ireland, but increased in frequency
      progressively throughout the second-half of that century. The reported numbers
      are likely to have minimised the real rates because of under-reporting.

PMID- 30115148
TI  - Evidence for the treatment of moderate depression: a systematic review.
AB  - OBJECTIVES: This study aims to investigate existing evidence for the
      effectiveness of psychological treatments and/or antidepressant medication as a
      treatment for those diagnosed with moderate levels of depression. METHODS: A
      PRISMA systematic review of articles using electronic research databases (2000
      2014) was conducted to identify studies investigating the effectiveness of
      psychotherapy and/or medication as a treatment for people with moderate levels of
      depression. Search terms included moderate depression, psychotherapy and/or
      medication, depressive disorders, antidepressants, psychotherapy, mental health
      services, and randomized-controlled trial (RCT). The included studies were then
      assessed, extracted, and synthesised. RESULTS: A total of 14 studies met the
      inclusion criteria (11 RCTs and three additional studies) for this review. The
      findings of the systematic review indicate that there is limited evidence
      available specific to the treatment of moderate depression and that this research
      seems to suggest that psychotherapy or combined treatment has a beneficial
      effect. CONCLUSIONS: Given that depression is one of the biggest challenges the
      world faces at present, further research is required to examine the effectiveness
      of treatment for different levels of depression severity.

PMID- 30115149
TI  - The collaborative assessment and management of suicide (CAMS): an important model
      for mental health services to consider.
AB  - The collaborative assessment and management of suicide (CAMS) model has been
      developed over 25 years providing mental health clinicians with a flexible,
      evidenced-based, collaborative and ethically informed way of addressing
      suicidality with service users. This paper briefly overviews the CAMS model and
      its advantages and advocates for its use in mental health services both
      nationally and internationally.

PMID- 30115150
TI  - Health student regard for substance-using patients as measured by the Medical
      Condition Regard Scale: a systematic review.
AB  - OBJECTIVES: As clinical impartiality is an accepted basic principle of ethical
      practice, any proactive exercises that may inform selection, training, clinical
      placements, and other interventions, which promote future positive and equitable
      professional conduct, thus guarding against future discriminatory attitudes are
      germane. Within this context, the purpose of this review was to identify trends
      and patterns in health student, namely future practitioners', regard for
      substance-using patients using the Medical Condition Regard Scale. METHODS: Six
      electronic databases were systematically searched for studies that used the
      Medical Condition Regard Scale as an outcome measure in assessing health student
      regard for drug-using patients. Academics who had published in this area were
      also consulted to recommend texts that would complement the above citation
      sourcing process. Following an elimination of duplicates, the application of
      inclusion and exclusion criteria, as well as conducting citation searches, 16
      studies were incorporated in the final review. Although the quality of all
      included studies was satisfactory, no study was free from a potential source of
      bias. RESULTS: This review found that patients with drug-use problems were
      consistently held in the lowest echelons of regard by trainee health
      practitioners. The impact of sex, age, year of course, and personal exposure to
      mental health difficulties in predicting negative regard was unclear.
      CONCLUSIONS: Unless addressed, patients with drug problems may have a high
      potential for future treatment marginalisation by tomorrow's health
      professionals. This scenario needs to be proactively managed by all stakeholders
      through a greater investment in educational and clinical training placement
      opportunities.

PMID- 30115151
TI  - From the Editor's Desk.

PMID- 30115152
TI  - A national survey of offending behaviour amongst intellectually disabled users of
      mental health services in Ireland.
AB  - BACKGROUND: Offenders with an intellectual disability pose a major challenge to
      Intellectual Disability Service providers in the Republic of Ireland. This is
      especially so as no national Forensic Intellectual Disability Service currently
      exists. The Forensic Intellectual Disability Working Group of the Irish College
      of Psychiatrists was established in order to take steps to address this issue by
      establishing the level of need for a Forensic Intellectual Disability Service in
      Ireland and developing a college position paper. No previous study has been
      carried out to measure offending behaviour amongst persons with an intellectual
      disability attending mental health services in Ireland. METHODS: A postal survey
      was undertaken targeting the lead clinicians of all Intellectual Disability
      Psychiatry, General Adult Psychiatry and Forensic Psychiatry Services in the
      Republic of Ireland. This survey requested anonymous data regarding service users
      with an intellectual disability and offending behaviour in this population.
      RESULTS: Data relating to 431 service users was returned. Those reported to
      engage in offending behaviour were predominantly young males. Assault was the
      most common offence type. A significant number of serious offences such as
      unlawful killing, sexual assault and arson were reported. CONCLUSIONS: There is
      an urgent need for the development of a Forensic Intellectual Disability Service
      in the Republic of Ireland. The current efforts of the National Forensic Mental
      Health Service to establish such a service by the creation of a post of
      Consultant Forensic Psychiatrist (special interest in intellectual disability)
      are to be welcomed.

PMID- 30115153
TI  - An evaluation of Access to Psychological Services Ireland: year one outcomes.
AB  - OBJECTIVES: To evaluate the clinical effectiveness and cost-effectiveness of
      Access to Psychological Services Ireland (APSI), a primary care adult psychology
      service. METHODS: A repeated measures design was used to evaluate the clinical
      outcomes of service users who completed an intervention. Psychological distress,
      depressive symptomatology and anxiety symptomatology were measured using the
      Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM), the Patient
      Health Questionnaire-9 (PHQ-9) and the Generalised Anxiety Disorder-7 (GAD-7),
      respectively. Self-reported health and economic outcomes were measured using the
      EQ-5D-3L and the Eco-Psy, respectively. RESULTS: A total of 381 adults were
      assessed as suitable for an APSI intervention, with 198 (52%) of these completing
      at least one intervention. Significant reductions in psychological distress were
      observed for completers of guided self-help and brief cognitive behavioural
      therapy, with service users also showing significant reductions in anxiety and
      depressive symptomatology. Reliable and clinically significant change on the CORE
      OM was observed for 67.9% of treatment completers. Service users reported
      significant improvements in their health status but did not show changes in their
      health service usage in the 3-month follow-up period. CONCLUSIONS: APSI provided
      an accessible service model that was clinically effective in managing a range of
      mild to moderate mental health difficulties. The cost-effectiveness of the
      service model may be enhanced by offering a wider range of high-throughput
      interventions and by increasing the treatment completion rate.

PMID- 30115154
TI  - Responding to mental health statutory drivers: experience of a low intensity
      cognitive behavioural therapy programme.
AB  - OBJECTIVES: Stress control (SC), a brief psycho-education course, was implemented
      to increase access to psychological therapies in line with Northern Irish mental
      health service statutory drivers. The first aim of this study was to gauge the
      efficacy of SC in a robust manner with clinical significance testing. The second
      aim was to assess whether demographics traditionally 'hard-to-reach' - males,
      younger adults and those from deprived areas - accessed SC. The third aim was to
      elucidate what prompted their access and the experiences of attendees at SC.
      METHODS: Attendees at SC were 170 adults over six iterations of the course. Pre-
      and post-questionnaires included the Depression Anxiety Stress Scales - 21,
      captured demographic details and qualitative feedback, which was subject to a
      mixed-methods analysis. RESULTS: SC attendees reported significant decreases on
      depression, anxiety and stress sub-scales post-intervention. Moreover, 38.71%
      (n=36) of attendees who completed SC exhibited clinically significant improvement
      afterwards on one or more sub-scale. Attendance figures for males, younger adults
      and those classified as socioeconomically deprived were modest. Patterns within
      the data suggested prospective success for targeting these cohorts. CONCLUSIONS:
      SC attracted people in need of mental healthcare input and affected quantifiable
      change within those people's lives, while satisfying statutory demands for
      service delivery in an accessible community context. Recommendations to increase
      engagement with those traditionally 'hard-to-reach' for psychological services
      are provided, which, if implemented, have the potential to achieve further
      compliance with Northern Irish mental health statutory drivers.

PMID- 30115155
TI  - The effectiveness of cognitive behavioural therapy for pain in childhood and
      adolescence: a meta-analytic review.
AB  - OBJECTIVES: A variety of chronic painful conditions are present in the paediatric
      population. Patients with chronic pain often experience considerable scepticism
      and avoidance by health care providers. This meta-analytic review aimed to
      utilise well-designed studies, in examining the effectiveness of cognitive
      behavioural therapy (CBT) in the treatment of chronic pain in children and
      adolescents. METHODS: Nine randomized controlled trial studies examining CBT for
      chronic pain were reviewed. Outcome measures were child reported pain intensity,
      pain duration and functional disability. RESULTS: CBT had a large effect on pain
      intensity for recurrent abdominal pain (RAP), a small effect on headaches, and a
      medium effect on fibromyalgia. CBT had a medium effect on pain duration across
      pain types. CBT had a large effect on functional disability for RAP, a small
      effect on fibromyalgia and a moderate effect on headaches. Findings are limited
      by the small number of studies and varied control conditions. CONCLUSIONS: CBT
      may be effective in reducing child reported pain symptomology. Future studies
      using a larger sample and examining the differential impact of varied control
      conditions are needed.

PMID- 30115156
TI  - Beneficence and non-maleficence: confidentiality and carers in psychiatry.
AB  - The editorial considers how psychiatrists can deal with concerns relating to
      confidentiality that are prominent in patients and their carers. Confidentiality
      is paramount but there are situations when it can be breached. Some of these
      relate to emergency situations, others apply in less compelling circumstances.
      The ethical principles relating to confidentiality will be discussed. An
      assessment of capacity is central to the person's ability to consent/refuse
      information gathering or disclosure. Even when capacity is present, there are
      strategies that psychiatrists can use to respect patient autonomy while meeting
      the needs of carers. The possibility of training in negotiating these should be
      considered, as should advance directives.

PMID- 30115157
TI  - Meditation - a two edged sword for psychosis: a case report.
AB  - Meditation is believed to have many health benefits apart from enhancing
      spiritual health. However, there is evidence that meditation may even lead to
      psychosis or worsen it in some cases. The aim of this paper is to present a case
      and discuss the role of meditation as a precipitating factor to psychosis. A 27
      year-old male presented with psychotic symptoms with a temporal correlation with
      meditation. He was then successfully treated with antipsychotic medication and is
      maintaining well. This case report highlights the possibility that intense
      meditation could precipitate psychosis in vulnerable individuals. However, there
      are several beneficial effects of meditation in patients with psychosis if
      practiced with caution.

PMID- 30115158
TI  - An evaluation of the effectiveness of 'Time to Adjust' a group-based cognitive
      behavioural-therapy (CBT) programme for patients recovering from cancer.
AB  - OBJECTIVES: 'Time to Adjust' (TTA) is a 6-week group-based cognitive-behavioural
      therapy programme for patients recovering from cancer. The TTA intervention is
      designed to facilitate patient's adjustment to life after cancer by enhancing
      existing coping skills, developing new coping skills and drawing on peer support
      within the context of group delivery of the programme. The study aims to explore
      patient psychological adjustment and to identify features of the intervention
      that patients find most beneficial. METHODS: This retrospective repeated measures
      design study represents a clinical evaluation of a group-based intervention
      routinely delivered by the Cancer Psychology Service at University Hospital
      Limerick. TTA was open to patients with a cancer diagnosis who had completed
      their surgery, radiotherapy and chemotherapy treatment by the programme start
      date. Patients self-referred and suitability for the programme was assessed by
      pre-programme clinical interview. Pre- and post-intervention data from 59
      participants was collected using self-report measures of stress and coping. A
      brief end-of-programme questionnaire provided descriptive feedback on patients'
      experience of the programme. RESULTS: Findings revealed favourable trends in the
      psychological adjustment of patients. Self-reported depression, anxiety and
      negative adjustment was lower post-TTA. CONCLUSIONS: This study indicates that
      TTA supports patients' psychological recovery from cancer with multiple
      components of the programme facilitating psychological adjustment. Findings
      support the delivery of group-based therapeutic interventions for this patient
      group. Future research could use in-depth post-intervention interviews for a
      richer understanding of the programme benefits. Longer-term follow-up in could
      examine the degree to which benefits are maintained over time.

PMID- 30115159
TI  - Clinical predictors of involuntary detention among voluntary inpatients in St
      Patrick's University Hospital (SPUH).
AB  - BACKGROUND: Few studies have described clinical characteristics of patients
      subject to an involuntary detention in an Irish context. The Irish Mental Health
      Act 2001 makes provision under Section 23(1), whereby a person who has voluntary
      admission status can be detained. Aims This study aimed to describe all
      involuntary admissions to St Patrick's University Hospital (SPUH) (2011-2013) and
      to evaluate clinical characteristics of voluntary patients who underwent Mental
      Health Act assessment during 2011 to determine differences in those who had
      involuntary admission orders completed and those who did not. METHODS: All uses
      of Mental Health Act 2001 within SPUH 2011-2013 were identified. All uses of
      Section 23(1) during 2011 were reviewed and relevant documents/case-notes
      examined using a pro forma covering clinical data, factors recognized to
      influence involuntary admissions and validated scales were used to determine
      diagnoses, insight, suicide and violence risk. RESULTS: Over 2011-2013, 2.5-3.8%
      of all admissions were involuntary with more detained after use of Section 23(1)
      than Section 14(2). The majority of initiations of Section 23(1) did not result
      in an involuntary admission (72%), occurred out of hours (52%) and many occurred
      early after admission (<1 week, 43%). Initiation of Section 23(1) by a consultant
      psychiatrist (p=0.001), suicide risk (p=0.03) and lack of patient insight into
      treatment (p=0.007) predicted conversion to involuntary admission. CONCLUSION:
      This study predicts a role for patient insight, suicide risk and consultant
      psychiatrist decision making in the initiation of Mental Health Act assessment of
      voluntary patients. Further data describing the involuntary admissions process in
      an Irish setting are needed.

PMID- 30115161
TI  - Atypical social cognitive processing in premotor Huntington's disease: a single
      case study.
AB  - BACKGROUND: We report the case of a 52-year-old male with pre-motor Huntington's
      disease (HD) who has undergone detailed clinical and neuropsychological
      examination. This patient's negative symptomatology and behavioural change are
      having a detrimental impact on his social, occupational and interpersonal life,
      in the absence of motor symptoms. METHODS: The patient has undergone repeat
      neuropsychological testing (T1 aged 50; T2 aged 52) with particular focus on
      executive function and social cognition on repeat testing. RESULTS: This case
      details a specific manifestation of HD relating to behavioural, psychiatric and
      social affective deficits. CONCLUSIONS: This case illustrates how social
      cognitive changes can occur in HD, months and even years prior to the onset of
      motor features and how such unrecognized deficits can have a deleterious impact
      on an individual's functional ability and lifestyle, before the disease is
      traditionally considered to have become manifest.

PMID- 30115160
TI  - Eating Disorder Examination Questionnaire (EDE-Q): norms for female university
      students attending a university primary health care service in Ireland.
AB  - OBJECTIVES: The Eating Disorder Examination Questionnaire (EDE-Q) is a self
      report questionnaire that is used to identify probable cases of eating disorders.
      Norms are needed for interpretation of scores. The aim of this study is to
      establish norms for the EDE-Q among female university students attending a
      university primary health care service in Ireland and to present prevalence of
      key eating disorder behaviours. METHODS: The EDE-Q was administered to a
      consecutive sample of 200 female students aged 18-30 years attending a university
      primary health care service. RESULTS: The mean global EDE-Q score was 1.51
      (s.d.=1.28). There was a positive association between body mass index and the
      global EDE-Q score; 5.8% of the sample scored in the clinically significant range
      on the global EDE-Q score. CONCLUSIONS: This study presents normative EDE-Q data
      for an Irish female university sample. These norms may inform clinicians and/or
      researchers in the evaluation of EDE-Q scores in Irish female university
      students.

PMID- 30115127
TI  - Epidemiology and patterns of tracheostomy practice in patients with acute
      respiratory distress syndrome in ICUs across 50 countries.
AB  - BACKGROUND: To better understand the epidemiology and patterns of tracheostomy
      practice for patients with acute respiratory distress syndrome (ARDS), we
      investigated the current usage of tracheostomy in patients with ARDS recruited
      into the Large Observational Study to Understand the Global Impact of Severe
      Acute Respiratory Failure (LUNG-SAFE) study. METHODS: This is a secondary
      analysis of LUNG-SAFE, an international, multicenter, prospective cohort study of
      patients receiving invasive or noninvasive ventilation in 50 countries spanning 5
      continents. The study was carried out over 4 weeks consecutively in the winter of
      2014, and 459 ICUs participated. We evaluated the clinical characteristics,
      management and outcomes of patients that received tracheostomy, in the cohort of
      patients that developed ARDS on day 1-2 of acute hypoxemic respiratory failure,
      and in a subsequent propensity-matched cohort. RESULTS: Of the 2377 patients with
      ARDS that fulfilled the inclusion criteria, 309 (13.0%) underwent tracheostomy
      during their ICU stay. Patients from high-income European countries (n =
      198/1263) more frequently underwent tracheostomy compared to patients from non
      European high-income countries (n = 63/649) or patients from middle-income
      countries (n = 48/465). Only 86/309 (27.8%) underwent tracheostomy on or before
      day 7, while the median timing of tracheostomy was 14 (Q1-Q3, 7-21) days after
      onset of ARDS. In the subsample matched by propensity score, ICU and hospital
      stay were longer in patients with tracheostomy. While patients with tracheostomy
      had the highest survival probability, there was no difference in 60-day or 90-day
      mortality in either the patient subgroup that survived for at least 5 days in
      ICU, or in the propensity-matched subsample. CONCLUSIONS: Most patients that
      receive tracheostomy do so after the first week of critical illness. Tracheostomy
      may prolong patient survival but does not reduce 60-day or 90-day mortality.
      TRIAL REGISTRATION: ClinicalTrials.gov, NCT02010073 . Registered on 12 December
      2013.

PMID- 30115162
TI  - Review of international clinical guidelines for adolescents on transition to
      Adult Mental Health Services and adults with attention-deficit hyperactivity
      disorder and their application to an irish context.
AB  - OBJECTIVES: To review the available clinical guidelines from Canada, North
      America, Europe and the United Kingdom for the diagnosis and management of
      attention-deficit hyperactivity disorder (ADHD) for adolescents previously
      diagnosed in Child and Adolescent Mental Health Services (CAMHS) on transition to
      Adult Mental Health Services (AMHS) and for adults presenting with a diagnostic
      query re-ADHD. This article seeks to apply the available guidelines to an Irish
      context. METHOD: Various clinical guidelines and consensus statements were
      identified by a literature search of PubMed, incorporating literature from the
      past 10 years from English speaking countries and inclusion of any additional
      guidelines of clinical relevance. A clinical guideline with specific reference
      for Irish clinicians was proposed for the diagnosis and management of adults
      presenting for the first time with a diagnostic query re-ADHD and also to include
      those young adults previously diagnosed in CAMHS on transition to AMHS.
      CONCLUSIONS: ADHD is a lifelong disorder, which if undiagnosed or untreated can
      lead to significant impairment resulting in a high economic cost for society.
      Stimulant medication is a first-line treatment option for adults with ADHD;
      however, some formulations are unlicensed in Ireland. Recent licensing of
      Atomoxetine, for both adolescents on transition and for adults with newly
      diagnosed ADHD is a welcome development. Third-line agents are rarely prescribed
      due to their side effect profiles and are prescribed off-label: It is important
      to establish clinical guidelines for an Irish context incorporating a
      biopsychosocial approach. Further discussion amongst clinicians and stakeholders
      is needed to plan service development.

PMID- 30115163
TI  - Impact of co-facilitated information programmes on outcomes for service users and
      family members: the EOLAS programmes (paper 2).
AB  - OBJECTIVE: The present study evaluated the impact on psychosocial outcome of
      parallel clinician and peer-led information programmes for people with a
      diagnosis of schizophrenia and bipolar disorder and for family members within an
      Irish context. METHODS: A sequential mixed method design was used. Quantitative
      data were collected using pre- and post-programme questionnaires followed by an
      integrated qualitative component involving semi-structured interviews after the
      programme. The questionnaires assessed knowledge, attitudes towards recovery,
      hope, support, advocacy and well-being. Interviews with participants,
      facilitators and project workers explored their experiences and views of the
      programme. Findings While a number of the questionnaires did not show a
      statistically significant change, findings from the interviews suggest that the1
      programmes had a number of positive outcomes, including increases in perceived
      knowledge, empowerment and support. Participants in both programmes valued the
      opportunity to meet people in similar circumstances, share their experiences,
      learn from each other and provide mutual support. CONCLUSION: The EOLAS
      programmes offer a novel template for communication and information sharing in a
      way that embodies the principles of collaboration and offers users and families a
      meaningful opportunity to become involved in service design, delivery and
      evaluation.

PMID- 30115164
TI  - An established practice in new surroundings: concepts, challenges, pitfalls and
      guidelines for NCHD Balint Groups.
AB  - Balint groups are now mandatory for psychiatry trainees. Balint groups have been
      in existence in General Practice for several decades. Providing Balint groups for
      Psychiatry Non Consultant Hospital Doctors brings with it challenges for the
      group leader and participants. Many of these challenges are common place in any
      form of group work, while others are unique to this cohort. This article
      describes these challenges. Guidelines which offer the the group the best chance
      of success, in the face of these common challenges, are discussed.

PMID- 30115166
TI  - A participatory approach to the development of a co-produced and co-delivered
      information programme for users of services and family members: the EOLAS
      programme (paper 1) - Corrigendum.

PMID- 30115165
TI  - A participatory approach to the development of a co-produced and co-delivered
      information programme for users of services and family members: the EOLAS
      programme (paper 1).
AB  - OBJECTIVE: The EOLAS programme is a peer and clinician-led mental health
      information programme on recovery from mental health difficulties, specifically
      for people with a diagnosis of schizophrenia spectrum or bipolar disorders, their
      family members and significant others. METHOD: This article, the first of a two
      part series, outlines the background to and the rationale behind the EOLAS
      programme, and traces the participatory process used to inform the development
      and implementation of the pilot phase of the project. The aims of the programme,
      and the overarching principles that guided its development, delivery and
      evaluation, including the set-up of the project steering group are outlined and
      discussed. Findings Two separate programmes, one for family members and one for
      service users were designed. In addition, participant and facilitator handbooks
      were developed for each programme, including a training programme for
      facilitators. CONCLUSION: Central to a recovery oriented service is the
      involvement of service users and families in the design and delivery of services.
      EOLAS is one potential model for achieving this aim.

PMID- 30115167
TI  - Impact of co-facilitated information programmes on outcomes for service users and
      family members: the EOLAS programmes (paper 2) - Corrigendum.

PMID- 30115168
TI  - The impact of a specialized inpatient and day patient group programme on clinical
      outcome in older adolescents and young adults with mental illness.
AB  - : Introduction Effective transition from child and adolescent mental health
      services (CAMHS) to adult services is one of the main challenges currently facing
      child psychiatry today The Young Adult 1Programme (YAP) based at St. Patrick's
      University Hospital Dublin, is a group based day programme especially designed to
      meet the needs of younger people aged 18-25 and support them through this
      difficult period. Aims To examine the effectiveness of participation in YAP for
      young adults with mental illness. To determine whether participation in
      particular aspects of the programme prove more beneficial and what factors might
      be associated with outcome. METHOD: All patients enrolled in YAP between 1
      September 2011 and 31 August 2012 were included in the study. Each patient was
      assessed using the Health of the Nation Outcome Scales (HONOS) and Global
      Assessment of Functioning (GAF) rating scale before beginning the programme and
      after discharge in order to evaluate improvement. The frequency of attendance at
      individual group sessions was recorded. Patient and illness variables were also
      recorded, for example demographics, diagnosis. RESULTS: A total of 101 service
      users were in enrolled in YAP during this 12-month period. Eight service users
      could not be used for analysis, as they did not have a complete data set, mostly
      due to failure to attend for discharge HONOS/GAF ratings Using a paired sample t
      test, there is a significant reduction in HONOS: Mean df=1.3, s.d.=1.09 (95%
      CI=1.08-1.53), p<0.001 Using a paired sample t-test, there is a significant
      increase in GAF: Mean df=9.25, s.d.=7.69 (95% CI=7.66-10.83), p<0.001
      Improvements in HONOS and GAF scores are significantly correlated with better
      attendance at the programme (p<0.04, <0.00 respectively). CONCLUSION: More
      attendance at YAP sessions correlates with better improvement in both HONOS and
      GAF rating scores.

PMID- 30115170
TI  - Correspondence.

PMID- 30115169
TI  - Monitoring of prolactin levels in children and adolescents prescribed
      antipsychotic medication: a complete audit cycle.
AB  - : Aims and methods Antipsychotics have proven benefits in children and
      adolescents with autism spectrum disorders. However, notwithstanding some
      therapeutic benefits significant side effects are associated with the use of
      antipsychotics, such as hyperprolactinaemia. We completed an audit cycle between
      April 2013 and December 2013 to evaluate the practice in the Beechpark Autism
      Service with respect to monitoring and managing hyperprolactinaemia in children
      and adolescents prescribed antipsychotics. The re-audit assessed whether the
      recommended guidelines and changes had been implemented. The National Institute
      for Health and Care Excellence guidelines were used as a gold standard for this
      audit. RESULTS: Basal determinations of serum prolactin improved significantly at
      the end of the audit cycle (28.6% v. 57%) with slight improvement in six monthly
      repeat prolactin monitoring (28.6% v. 39.1%) showing some change in clinical
      practice. However, there was minimal improvement in managing hyperprolactinaemia
      (0% v. 12.5%). Clinical implication There is growing awareness about
      hyperprolactinaemia associated with the use of antipsychotic medication in
      children and adolescents and the long-term effects. Clear documented guidelines
      will help increase and improve the monitoring and management of
      hyperprolactinaemia in these groups of patients. However, more needs to be done
      in improving the practice of monitoring and managing hyperprolactinaemia in
      children and adolescent prescribed antipsychotic medication giving the documented
      long-term effects.

PMID- 30115171
TI  - Psychotropic prescribing patterns among adolescents in Northern Ireland
      presenting with psychotic symptoms during a 5-year period.
AB  - OBJECTIVE: To report new prescriptions of psychotropic medications among
      adolescents presenting with new onset psychotic symptoms during a 5-year period.
      METHODS: The Northern Ireland Early Onset Psychosis Study is a naturalistic
      longitudinal observational study of patients with an early onset first psychotic
      episode. All patients aged <18 years presenting to specialist mental health
      services across Northern Ireland with new onset psychotic symptoms between 2001
      and 2006 were recruited (n=113). Clinical case notes were analysed
      retrospectively for details of subsequent treatment with psychotropic
      medications. RESULTS: A total of 100 patients (88.5%) were prescribed some form
      of psychotropic medication. Over three-quarters of patients received an
      antipsychotic as their first medication. Risperidone (45.8%), olanzapine (24.0%)
      and chlorpromazine (12.5%) were the most commonly prescribed first-line
      antipsychotic medications. Of a total of 160 antipsychotic prescriptions, 81
      (50.6%) were off-label. Prescriptions were most likely to have been deemed off
      label owing to medications not being licensed in under-18s (71.6% of off-label
      prescriptions) but other reasons were medications being used outside licensed age
      ranges (23.5%) and outside licensed indications (4.9%). CONCLUSIONS: This is the
      first study examining psychotropic prescribing patterns in a complete sample of
      all children and adolescents presenting with early onset psychotic episodes in a
      single geographical area. The observation of risperidone as the most commonly
      prescribed antipsychotic was in keeping with previous studies in child and
      adolescent populations. Rates of off-label prescribing were lower than previously
      observed although our study was the first to investigate off-label prescribing
      solely in children and adolescents presenting with psychotic symptoms.

PMID- 30115172
TI  - Visual hallucinations in the elderly: a case series and discussion of aetiology
      and treatment.
AB  - BACKGROUND: Visual hallucinations are a common phenomenon, among the older adult
      population. They can be functional or organic in aetiology. However, new onset
      visual hallucinations in this population are strongly suggestive of organic brain
      disease. Visual impairment, cerebrovascular disease and Parkinson's disease are
      three causes of visual hallucinations, considered in this case series. The
      evidence in the literature, for the treatment of these conditions is scant at
      best. There is a paucity of randomised controlled trials available concerning
      possible therapeutic options. Aims/Methods We describe three case reports of
      visual hallucinations due to diverse underlying aetiologies. We then discuss the
      aetiologies of visual hallucinations in general and then in these particular
      cases and finally include results of a literature search examining the available
      evidence for any therapeutic options proposed. RESULTS: Our three cases have
      different, underlying aetiologies. One case is of Charles Bonnet syndrome. The
      next is of visual hallucinations associated with vascular dementia. The final
      case is of visual hallucinations associated with Parkinson's disease. The first
      two cases are of particular interest due to the efficacy of Amisulpride in both
      clinical scenarios. CONCLUSIONS: Visual hallucinations are a common phenomenon in
      the elderly population They can be due to a myriad of underlying causes. There
      are a number of neurochemical factors and neuroanatomical structures implicated.
      The evidence for psychopharmacological interventions is scanty. Randomised
      controlled trials are lacking in the area. An interesting finding in this case
      series, was of the clinical utility of Amisulpiride. Given this agent's unique
      psychopharmacological profile it is possible that it may be efficacious in other
      cases of visual hallucinations associated with particular neurochemical factors.

PMID- 30115173
TI  - Using electronic medical records to determine prevalence and treatment of mental
      disorders in primary care: a database study.
AB  - OBJECTIVES: With prevention and treatment of mental disorders a challenge for
      primary care and increasing capability of electronic medical records (EMRs) to
      facilitate research in practice, we aim to determine the prevalence and treatment
      of mental disorders by using routinely collected clinical data contained in EMRs.
      METHODS: We reviewed EMRs of patients randomly sampled from seven general
      practices, by piloting a study instrument and extracting data on mental disorders
      and their treatment. RESULTS: Data were collected on 690 patients (age range 18
      95, 52% male, 52% GMS-eligible). A mental disorder (most commonly anxiety/stress,
      depression and problem alcohol use) was recorded in the clinical records of 139
      (20%) during the 2-year study period. While most patients with the common
      disorders had been prescribed medication (i.e. antidepressants or
      benzodiazepines), a minority had been referred to other agencies or received
      psychological interventions. 'Free text' consultation notes and 'prescriptions'
      were how most patients with disorders were identified. Diagnostic coding alone
      would have failed to identify 92% of patients with a disorder. CONCLUSIONS:
      Although mental disorders are common in general practice, this study suggests
      their formal diagnosis, disease coding and access to psychological treatments are
      priorities for future research efforts.

PMID- 30115174
TI  - Stigma and treatment of eating disorders in Ireland: healthcare professionals'
      knowledge and attitudes.
AB  - OBJECTIVES: This study examines aspects of healthcare professionals' knowledge
      and attitudes about eating disorders (EDs), which might impede the effective
      detection or treatment of EDs in Ireland. METHODS: A total of 1,916 healthcare
      professionals were invited to participate in a web-based survey. Participants
      were randomly allocated to view one of five vignettes depicting a young person
      with symptoms consistent with anorexia nervosa, bulimia nervosa, binge-eating
      disorder, depression or type 1 diabetes. Study-specific questions examined
      participants' responses to the vignettes and ED knowledge and experience.
      RESULTS: In total, 171 clinicians responded (9% response rate). Participants had
      an average of 15.8 years of clinical experience (s.d.=9.2) and included
      psychiatrists, GPs, psychologists and counsellors. Although participants'
      knowledge of EDs was moderately good overall, responses showed poor recognition
      of the symptoms of EDs compared with depression [chi 2 (4, n=127)=20.17,
      p<0.001]. Participants viewed EDs as chronic disorders that primarily affected
      females. Participants believed that clinicians like working with patients with
      depression and diabetes more than with AN patients [F (4,101)=5.11, p=0.001].
      Among the professionals surveyed, psychiatrists were the most knowledgeable about
      EDs [F (4,82)=9.18, p<0.001], and were more confident in their ability to
      diagnose and treat EDs than professionals of all other disciplines, except
      psychologists [F (4,85)=8.99, p<0.001]. Psychiatrists were also the most
      pessimistic about ED patients' long-term life prospects [chi 2 (4, n=65)=15.84,
      p=0.003]. CONCLUSIONS: This study recommends that specific attention should be
      given to EDs in professional educational programmes across healthcare
      disciplines. This training should not be restricted to improving healthcare
      professionals' knowledge of EDs, but should also strive to increase service
      providers' awareness of how their own potentially stigmatising attitudes can
      undermine engagement with treatment.

PMID- 30115175
TI  - The Irish Journal of Psychological Medicine: expanding horizons, moving on.

PMID- 30115176
TI  - Opting out of IJPM printed copies.

PMID- 30115177
TI  - Opinions of key stakeholders concerning involuntary admission of patients under
      the Mental Health Act 2001.
AB  - OBJECTIVES: To evaluate and compare the opinions of key stakeholders involved in
      the involuntary admission and treatment of patients under the Mental Health Act
      (MHA) 2001 regarding their views towards the operation of the legislation.
      METHODS: We employed a descriptive survey design. A questionnaire was distributed
      to stakeholders involved in the operation of the MHA 2001 (except service users,
      whose views were explored in a separate qualitative study) via paper or online
      versions evaluating their opinions regarding the operation of the MHA 2001 in
      relation to assessment, care, rights, transfer and information available.
      RESULTS: Stakeholders agreed that in their opinion that patients generally
      benefit from the care they receive (79%) and that the MHA 2001 ensures an
      independent and fair review of the person's detention (65%). However, only 23% of
      stakeholders were satisfied with the process of transferring patients to hospital
      and with the clinical assessment procedures therein (37%), with the greatest
      levels of dissatisfaction amongst Gardai (Police), general practitioners (GPs)
      and family members. CONCLUSIONS: While the introduction of the MHA 2001 has
      assisted delivery of care to patients with improved adherence to international
      human rights frameworks applicable at the time of its enactment, substantial
      dissatisfaction with the implementation of the MHA 2001 in practice is
      experienced by stakeholders particularly at the distressing phase of clinical
      assessment and transfer to hospital.

PMID- 30115178
TI  - A comparison of mental health legislation in five developed countries: a
      narrative review.
AB  - OBJECTIVES: To describe similarities and differences in mental health legislation
      between five jurisdictions: the Republic of Ireland, England and Wales, Scotland,
      Ontario (Canada), and Victoria (Australia). METHODS: An in-depth examination was
      undertaken focussing on the process of involuntary admission, review of Admission
      Orders and the legal processes in relation to treatment in the absence of patient
      consent in each of the five jurisdictions of interest. RESULTS: All jurisdictions
      permit the detention of a patient if they have a mental disorder although the
      definition of mental disorder varies between jurisdictions. Several additional
      differences exist between the five jurisdictions, including the duration of
      admission prior to independent review of involuntary detention and the role of
      supported decision making. CONCLUSIONS: Across the five jurisdictions examined,
      largely similar procedures for admission, detention and treatment of involuntary
      patients are employed, reflecting adherence with international standards and
      incorporation of human rights-based principles. Differences exist in relation to
      the criteria to define mental disorder, the occurrence of automatic review
      hearings in a timely fashion after a patient is involuntarily admitted and the
      role for supported decision making under mental health legislation.

PMID- 30115179
TI  - Service users' perspective of their admission: a report of study findings.
AB  - OBJECTIVES: The 'Service Users' Perspective of their Admission' study examined
      voluntarily and involuntarily admitted services users' perception of coercion
      during the admission process and whether this was associated with factors such as
      the therapeutic alliance, satisfaction with services, functioning and quality of
      life. This report aims to collate the findings of the study. METHODS: The study
      was undertaken across three community mental health services in Ireland.
      Participants were interviewed before discharge and at 1 year using the MacArthur
      Admission Experience. Caregivers of participants were interviewed about their
      perception of coercion during the admission. RESULTS: A total of 161 service
      users were interviewed and of those admitted involuntarily, 42% experienced at
      least one form of physical coercion. Service users admitted involuntarily
      reported higher levels of perceived coercion and less procedural justice than
      those admitted voluntarily. A total of 22% of voluntarily admitted service users
      reported levels of perceived coercion comparable with involuntarily admitted
      service users and this was associated with treatment in a secure ward or being
      brought to hospital initially under mental health legislation. In comparison with
      the service user, caregivers tended to underestimate the level of perceived
      coercion. The level of procedural justice was moderately associated with the
      therapeutic relationship and satisfaction with services. After 1 year, 70%
      experienced an improvement in functioning and this was not associated with the
      accumulated level of coercive events, when controlled for confounders.
      CONCLUSIONS: This study has provided valuable insights into the perceptions of
      coercion and can help inform future interventional studies aimed at reducing
      coercion in mental health services.

PMID- 30115180
TI  - Service users' experiences of mental health tribunals in Ireland: a qualitative
      analysis.
AB  - OBJECTIVES: To explore the mental health tribunal experiences of people admitted
      involuntarily under the Mental Health Act 2001. METHODS: Employing a qualitative
      descriptive study design, data were collected from 23 service users who had
      experienced mental health tribunals during a recent involuntary admission. Face
      to-face semi-structured interviews were conducted ~3 months post-revocation of
      their involuntary admission order. Data were analysed using an inductive thematic
      process. RESULTS: The majority of participants reported mixed experiences
      comprising positive and negative aspects in relation to information provision,
      emotional support and an inclusive atmosphere. Some participants reported
      receiving accessible information about the tribunal process, felt emotionally
      supported throughout, and encountered respectful and dignifying practices during
      the tribunal proceedings. However, many participants described experiencing non
      inclusive practices, reported feeling ill-informed regarding the tribunal
      process, emotionally unsupported during and after the tribunal, and distressed by
      what they perceived as adversarial tribunal proceedings. CONCLUSIONS: Systemic
      changes could ensure that the positive experiences encountered by the minority of
      participants in this study are more consistently experienced. Ongoing education
      and training of stakeholders in the provision of inclusive tribunal practices,
      and the provision of accessible information and emotional support to service
      users through the stages of the involuntary admission process appear likely to be
      beneficial. Service users should automatically be offered the option of having a
      support person of their choosing present during tribunals.

PMID- 30115181
TI  - Voluntary and involuntary psychiatric admissions in a suburban area: comparison
      with national rates, diagnosis and other correlates of involuntary admission
      status.
AB  - OBJECTIVES: To establish if the relatively low rate of involuntary psychiatric
      admission in a suburban area between 2007 and 2011 was maintained in 2014/2015,
      and explore key correlates of involuntary status. METHODS: We used existing
      hospital records and data sources to extract rates and selected potential
      correlates of voluntary and involuntary admission in south west Dublin (catchment
      area: 273 419 people) over 18 months in 2014/2015 and compared these with
      published national data from the census and Health Research Board. RESULTS: The
      rate of involuntary admission in the suburban area studied between 2007 and 2011
      was 33.8 involuntary admissions per 100 000 population annually, which was lower
      than the national rate (48.6). By 2014/2015, the rate of involuntary admission in
      this area had risen to 46.8 involuntary admissions per 100 000 population
      annually, similar to the national rate (44.9). Nevertheless, the overall
      (voluntary and involuntary) admission rate in the suburban area (346.7 admissions
      per 100 000 population annually) was still lower the national rate (387.9), owing
      to a lower rate of voluntary admission in the suburban area (299.9) compared to
      Ireland as a whole (342.9). Multi-variable testing demonstrated that diagnosis
      was the strongest driver of involuntary admission in the suburban area: this area
      had 28.5 involuntary admissions per 100 000 population annually with
      schizophrenia or related disorders, compared to 18.9 nationally. Schizophrenia
      and related disorders accounted for 60.9% of involuntary admissions in the
      suburban area compared to 42.1% nationally. CONCLUSIONS: Schizophrenia is the
      strongest driver of involuntary admission in the suburban area in this study.

PMID- 30115182
TI  - Coercion: an understudied issue in mental health.
AB  - Coercion in mental health services is a controversial practice, yet it is a
      relatively understudied area. This special themed edition draws upon research
      from the international community with the aim of addressing issues related to
      coercion and involuntary admission. The issue covers topics such as community
      treatment orders, service users' perspectives, alternative models of involving
      service users in their treatment, and future directions for coercion research. It
      is hoped that this edition will encourage funding and inspire future research on
      this important topic.

PMID- 30115183
TI  - A randomized study of a smartphone application compared with booklet to improve
      service user's knowledge of their legal rights.
AB  - BACKGROUND: The Mental Health Act 2001 has introduced significant changes to the
      process of admission to hospital for individuals affected by mental health
      disorders. This study aimed to determine whether a newly designed smartphone
      application could result in an improvement in service users' knowledge of their
      rights compared with the paper booklet. METHODS: This was a randomized study
      conducted in an outpatient and day-hospital in North Dublin. Participants were
      randomized to receive the information booklet as either a smartphone application
      or in the paper form. A questionnaire which was scored from 0 to 10 was devised
      and was completed at baseline and at 1-week follow-up. RESULTS: A total of 42
      individuals completed the baseline and follow-up questionnaire and of these,
      53.7% were female and the mean age was 38.2 years (s.d.+/-13.5). A total of 34.1%
      had a diagnosis of a psychotic disorder, 29.3% had a depressive disorder and 22%
      had bipolar-affective disorder. The mean score before the intervention in the
      total group was 3.5 (s.d.+/-2.2) and this increased to 5.8 (s.d.+/-2.2) at follow
      up. Participants randomized to the smartphone application improving by a mean of
      2.5 (s.d.+/-2.5), while those randomized to the booklet improving by a mean of
      2.3 (s.d.+/-2.6), which was not statistically significant. CONCLUSIONS: Both
      forms of the information booklet showed improvement in service users' knowledge
      of their legal rights. It is possible that each individual will have preference
      for either a paper form or a smartphone form and this study suggests that both
      forms should be offered to each individual service user.

PMID- 30115185
TI  - Differences between DSM-IV and DSM-5 as applied to general adult psychiatry.

PMID- 30115184
TI  - Psychiatric illness, medication and driving: an audit of documentation.
AB  - OBJECTIVES: Guidelines on advising patients on fitness to drive have been
      published recently by the Road Safety Authority in collaboration with the Royal
      College of Physicians of Ireland. The aim of this audit is to assess if the new
      guidelines are being adhered to. METHOD: Examination of the documentation and
      adherence to the guidelines in the inpatient psychiatric unit, Mayo General
      Hospital. RESULTS: Of the 100 patients included in audit cycle one, none had any
      specific documentation about driving. One patient was admitted with alcohol
      misuse and was driving. On re-auditing, following presentation at academic
      meeting and education of team members on the guidelines, there was a minor
      improvement of 7%. CONCLUSION: There was no significant difference in
      documentation on re-audit. However, an increase of 7% is nonetheless encouraging.
      Information concerning driving should be a standard part of advice given to all
      psychiatric patients.

PMID- 30115186
TI  - Monitoring of extrapyramidal side effects in patients on antipsychotic treatment:
      a completed audit cycle.
AB  - BACKGROUND: Movement disorders are a common problem in those receiving
      antipsychotic medication. Clinical guidelines recommend that these side-effects
      are monitored regularly throughout treatment. However, due to a lack of training,
      clinician confidence levels in assessment are often low and regular monitoring
      may be neglected. Aims To audit current practice in our services regarding
      monitoring of extrapyramidal side effects (EPSE) and improve monitoring through
      education of clinicians. METHOD: The clinical records of patients receiving
      antipsychotic treatment, seen in the outpatient clinic over a 2-week period, were
      reviewed. Data were collected on whether or not EPSE had been assessed. A re
      audit was undertaken following a teaching session. RESULTS: Documentation
      regarding EPSE was present in only 14% of patient records. Following a teaching
      session, the overall level of documentation of EPSE rose to 42%, with rates of
      assessment dramatically improving in non-consultant hospital doctors. CONCLUSION:
      In our practice, clinicians are generally poor to assess and record EPSE.
      However, rates of assessment improved significantly following a teaching session,
      especially in NCHDs.

PMID- 30115187
TI  - Are parents and children satisfied with CAMHS?
AB  - BACKGROUND: Client Satisfaction with services is an important predictor of health
      care seeking, treatment compliance and health status outcome. Given that both
      parents and young people may have different views of services offered, this study
      examines both perspectives with respect to Child and Adolescent Mental Health
      Services (CAMHS) in Ireland. METHOD: Following ethical approval, the Client
      Satisfaction Questionnaire-8 (CSQ-8) were sent to all open cases attending three
      urban CAMHS. Returned questionnaires were received from 426 (280 parents and 146
      adolescents) giving a response rate of 49%. RESULTS: No significant differences
      were observed between parents and adolescents regarding general satisfaction with
      CAMHS (Mann-Whitney U-test; Z=-0.255; p=0.799) with a range of good and excellent
      ratings between 77.1% (for the extent that program met user's needs) and 93.1%
      (for recommendation of program to a friend). Significant positive associations
      were found between age of child (Spearman's rho=0.159; p=0.017), receiving a
      diagnosis (Mann-Whitney U-test; Z=-2.14; p=0.032), frequent attendance (chi
      2=8.74; df=3; p=0.033) and living in close proximity to the service (chi 2=9.24;
      df=3; p=0.026). There was a strong negative correlation between reduction in
      impairment and levels of satisfaction (rho=-0.44, n=275, p<0.000). Waiting time
      or duration in service were not associated with CSQ and 53% (145) requested
      clinic opening hours outside of 09:00 a.m. to 17:00 p.m. CONCLUSION: Regular user
      feedback, a robust and distinct measure of service quality, will ensure the
      development of effective, accessible, client-centered and responsive services,
      which can evolve in partnership with families and young people.

PMID- 30115188
TI  - Psychiatric shades of grey: mirtazapine-induced hair discoloration and hair loss.
AB  - : Introduction Mirtazapine is indicated in the treatment of major depressive
      disorder particularly in selective serotonin re-uptake inhibitors resistance. Its
      effect on hair loss is rare with no previous documented effect on hair colour.
      METHOD: Review of relevant literature and description of a case report of a 54
      year-old male patient who developed alopecia and hair discoloration after
      initiation of mirtazapine treatment. RESULTS: Upon cessation of mirtazapine
      treatment full restoration of hair colour and regrowth of hair was attained
      within 10 weeks. Discussion There was clear temporal relationship between
      experiencing hair loss and commencing mirtazapine treatment. No other more likely
      medical reason to explain such experience was established. A noticeable
      restoration of the hair colour occurred following mirtazapine cessation.
      CONCLUSION: Mirtazapine is associated with hair discoloration and hair loss. The
      possibility of such distressing adverse effects needs to be conveyed to patients
      by clinicians and to be further explored by researchers.

PMID- 30115189
TI  - The challenges of diagnosis and treatment of dementia in Down's syndrome.
AB  - OBJECTIVES: People with Down syndrome (DS) are at high risk for developing
      dementia and early diagnosis is vital in enhancing quality of life. Our aim was
      to compare our practice to consensus recommendations on evaluation, diagnosis and
      pharmacological treatment of individuals with DS who develop dementia. We also
      aimed to establish the average time taken to make a diagnosis of dementia and to
      commence pharmacotherapy, and to assess tolerability to acetylcholinesterase
      inhibitors. METHODS: Retrospective chart review in an exhaustive sample
      containing all current service users attending our service with DS and a
      diagnosis of dementia (n=20). RESULTS: The sample was 75% female and 70% had a
      moderate intellectual disability. The average age at diagnosis of dementia was
      52.42 years old. The average time to diagnosis from first symptom was 1.13 years
      and the average time to commence pharmacotherapy was 0.23 years. A total of 17
      patients commenced on acetylcholinesterase inhibitors, and of these seven
      discontinued medication due to side-effects or lack of efficacy. CONCLUSIONS: The
      results on anticholinesterases add to the limited pool of data on treatment of
      dementia in DS. There was an identified need to improve the rates of medical,
      vision and hearing assessments, and prospective screening. Deficiencies in
      screening and diagnosis may be addressed by implementing a standardised dementia
      assessment pathway to include prospective screening and longitudinal assessment
      using easily administered scales. We highlight the importance of improving the
      diagnostic process, as a vital window of opportunity to commence a comprehensive
      care plan may be lost.

PMID- 30115190
TI  - Diabetes and brain health: implications for practice.
AB  - BACKGROUND: It is widely accepted that people with mental illness have increased
      risk of cardiometabolic complications such as obesity and type 2 diabetes
      mellitus. What is less well known is that individuals with diabetes have an
      increased risk of brain health complications including depression, cognitive
      impairment and dementia. These conditions can adversely influence disease self
      management and further increase risk of other diabetes complications. Aim The aim
      of this paper is to highlight the increased risk of brain health complications in
      populations with diabetes in order to promote awareness of such complications
      among healthcare professionals and encourage timely intervention. METHODS: An
      overview of the prevalence and potential mechanisms linking depression and
      cognitive impairment with diabetes as well as implications for detection,
      management and brain health protection, based on a narrative review of the
      literature. CONCLUSIONS: Early detection and effective management of depression
      and cognitive impairment among individuals with diabetes has the potential to
      minimise adverse health outcomes. In order to promote screening healthcare
      professionals caring for individuals with diabetes in all settings must be aware
      of the increased risk of brain health complications in this vulnerable
      population.

PMID- 30115192
TI  - Offering support to the general public by building CBT-based life skills: lessons
      learnt from an initial evaluation.
AB  - : AimsCognitive behavioural therapy (CBT) is effective for symptoms of mild to
      moderate depression yet access to such therapy is frequently limited. An
      alternative to traditional ways of delivering CBT is lower intensity methods
      based on self-help principles, using written CBT resources, in a group or class
      setting. Aware, the Irish National charity providing support to people
      experiencing depression, has implemented a 6-week CBT-based group programme which
      has been independently evaluated to demonstrate its effectiveness using
      quantitative and qualitative measures. METHOD: Two outcome measures (the Patient
      Health Questionnaire - PHQ-9, and Generalised Anxiety Disorder - GAD-7) were
      completed and analysed using a matched pairs t-test in respect of all
      participants at three intervals across the programme. Qualitative feedback was
      also sought upon completion of the course and offered insight into significant
      change and individual impact of the programme. RESULTS: A total of 2289
      individuals nationwide registered for the programme through the Aware website
      with 1885 completing the 6 weeks. There was an average attendance of 67% for the
      6-week programme. Statistically significant reductions in terms of scores of
      depression and anxiety were seen upon completion but earlier trends towards
      improvement were noted. CONCLUSION: Completion of a 6-week Life Skills Programme
      has been associated with a reduction from moderately severe to mild scores in
      relation to both depressive and anxiety symptoms. Longitudinal follow-up will be
      required to determine if the effectiveness of the intervention is maintained but
      CBT-based group programmes may represent a useful alternative to traditional
      services to treat clinically significant depression.

PMID- 30115191
TI  - Prevalence of housing needs among inpatients: a 1 year audit of housing needs in
      the acute mental health unit in Tallaght Hospital.
AB  - OBJECTIVE: There is a dearth of information relating to the prevalence of housing
      needs among psychiatric in-patients in Ireland. Most of the information we have
      to date emerged as a result of attempts to plan for the closure of old
      psychiatric hospitals and inappropriate community residences. This study sought
      to identify the prevalence of housing needs among in-patients in the acute
      psychiatric unit in Tallaght Hospital. METHODS: Each week, over a 12-month
      period, nursing managers and/or key nurses who knew the patients well were asked
      for numerical data. Information was collected on the numbers of in-patients with
      accommodation needs, number of delayed discharges due to accommodation needs and
      number of discharges to homeless accommodation in the previous week. RESULTS: On
      average, 38% of in-patients had accommodation related needs at any one time. Most
      (98%) of delayed discharges had accommodation related needs. Delayed discharge in
      patients with accommodation needs accounted for 28% of all inpatients and for 72%
      of all inpatients with accommodation related needs. CONCLUSIONS: Accommodation
      need among psychiatric in-patients is underreported. Housing need data should be
      routinely collected and effective interagency strategies developed to address
      housing needs.

PMID- 30115193
TI  - Dimensional thinking in psychiatry in the era of the Research Domain Criteria
      (RDoC).
AB  - The biological mechanisms underlying psychiatric diagnoses are not well defined.
      Clinical diagnosis based on categorical systems exhibit high levels of
      heterogeneity and co-morbidity. The Research Domain Criteria (RDoC) attempts to
      reconceptualize psychiatric disorders into transdiagnostic functional dimensional
      constructs based on neurobiological measures and observable behaviour. By
      understanding the underlying neurobiology and pathophysiology of the relevant
      processes, the RDoC aims to advance biomarker development for disease prediction
      and treatment response. This important evolving dimensional framework must also
      consider environmental factors. Emerging evidence suggests that gut microbes
      (microbiome) play a physiological role in brain diseases by modulating
      neuroimmune, neuroendocrine and neural signalling pathways between the gut and
      the brain. The integration of the gut microbiome signature as an additional
      dimensional component of the RDoC may enhance precision psychiatry.

PMID- 30115194
TI  - Hunger strikes in prisons: a narrative systematic review of ethical
      considerations from a physician's perspective.
AB  - OBJECTIVES: We sought to identify and review published studies that discuss the
      ethical considerations, from a physician's perspective, of managing a hunger
      strike in a prison setting. METHODS: A database search was conducted to identify
      relevant publications. We included case studies, case series, guidelines and
      review articles published over a 20-year period. Non-English language
      publications were translated. RESULTS: The review found 23 papers from 12
      jurisdictions published in five languages suitable for inclusion. CONCLUSIONS:
      Key themes from included publications are identified and summarised in the
      context of accepted guidelines from the World Medical Association. Whilst there
      seems to be an overall consensus favouring autonomy over beneficence, tensions
      along this fine balance are magnified in jurisdictions where legislation leads to
      a dual loyalty conflict for the physician.

PMID- 30115195
TI  - Client personal recovery and recovery orientation of an Irish suicide
      intervention charity.
AB  - BACKGROUND: Recovery is a key goal for individuals, and services' recovery
      orientation can facilitate this process. The independent mental health sector is
      increasingly important in Ireland, particularly in counselling and suicide
      prevention. We aimed to evaluate Pieta House as a recovery-oriented service
      through clients' self-rated recovery; and clients' and therapists' evaluation of
      the service. METHODS: Clients completing therapy over a 3-month period were
      invited to complete the Recovery Assessment Scale (RAS) and the Recovery Self
      Assessment-Revised (RSA-R). Therapists completed the RSA-R staff version.
      RESULTS: Response rate was 36.7% for clients (n=88), 98% for therapists (n=49).
      Personal recovery was endorsed by 73.8% of clients, with highest agreement for
      factors 'Willingness to Ask for Help' (84.5%), and 'Reliance on Others' (82.1%).
      A smaller number agreed with factors 'Personal Confidence and Hope' (61.3%) and
      'No Domination by Symptoms' (66.6%). Clients' and therapists' evaluation of the
      service showed high levels of agreement with factors of 'Choice' (90.9% clients,
      100% therapists); 'Life Goals' (84.1% clients, 98% therapists) and 'Individually
      Tailored Services' (80.6% clients, 79.6% therapists). Client involvement in
      service management had the lowest level of agreement (36.4% clients, 30.6%
      therapists). Clients' self-rated recovery correlated with their rating of the
      service (correlation value 0.993, p=0.01). CONCLUSIONS: Clients' self-rated
      recovery and the recovery orientation of Pieta House were rated highly, with
      areas for improvement in service user involvement, peer support and advocacy. The
      correlation of personal recovery and recovery orientation of the service may
      merit further study.

PMID- 30115196
TI  - Anxiety and depression among patients with alcohol dependence: co-morbid or
      substance-related problems?
AB  - OBJECTIVES: There are conflicting reports on the levels of anxiety and depression
      in individuals with alcohol problems and whether these conditions are substance
      related or independent of the alcohol problem. The aim of this study was to
      characterise rates of co-morbid psychiatric symptoms among a group of individuals
      commencing treatment for alcohol dependence, and to examine the stability of
      these symptoms following treatment of the alcohol problem. METHODS: Symptoms of
      anxiety and depression were examined in a group of individuals (n=93) undergoing
      residential treatment for alcohol dependence. Symptoms were measured at treatment
      entry and again at treatment completion using the Beck Anxiety Inventory and the
      Beck Depression Inventory - II. RESULTS: High levels of anxiety and depressive
      symptoms were reported at treatment entry, but on completion of treatment (28
      days later) the majority of participants were no longer reporting symptoms
      suggestive of a possible co-morbid condition. CONCLUSIONS: The significant change
      in rates of reported symptoms following completion of treatment suggests that a
      large proportion of symptoms reported at treatment entry were substance related.
      Diagnosing co-morbid conditions is best left until after a period of abstinence
      during which the alcohol problem has been treated. Assessing for co-morbidity at
      time of treatment seeking is likely to result in inappropriate co-morbid
      diagnoses being made and inappropriate or unnecessary treatments being prescribed
      for such individuals.

PMID- 30115197
TI  - Client personal recovery and recovery orientation of an Irish suicide
      intervention charity - Corrigendum.

PMID- 30115198
TI  - The association of dissociative symptoms with exposure to trauma.
AB  - BACKGROUND: The Khyber Pakhtunkhwa province of North-West Pakistan has endured
      increased levels of violence in recent years. The psychological sequelae of such
      trauma including the presence of dissociative symptoms has been minimally
      investigated to date. The study examines psychopathology experienced including
      the presence of dissociative symptoms, and ascertain what factors are potentially
      predictive of these symptoms. METHOD: Third-level students (n=303) completed
      psychometric instruments relating to their experience of traumatic events and
      assessed depression, anxiety and dissociative symptoms. RESULTS: Symptoms
      suggestive of post-traumatic stress disorder were evident in 28% of individuals.
      Symptoms relating to intrusive experiences and alterations in reactivity
      predicted dissociative, depressive and anxiety symptoms (p<0.01). CONCLUSION:
      Trauma related to violence in this study was associated with significant
      pathology including dissociative symptoms. Identification and subsequent
      treatment of dissociative symptoms in individuals who have experienced trauma,
      may have a significant ameliorating effect on levels of functioning and thus
      should be included in clinical assessment.

PMID- 30115199
TI  - Are we finally making progress with suicide and self-harm? An overview of the
      history, epidemiology and evidence for prevention.
AB  - Ireland's suicide rate is falling, but suicide and self-harm remain substantial
      societal problems. It is not possible to predict suicide at the level of the
      individual but good primary care, good mental health care and good social care
      all likely reduce risk. In terms of targeted interventions, public health
      measures, such as paracetamol pack size regulations, have the best evidence base
      to support them. Despite increased public and professional discussion, much
      remains to be done to provide effective, coordinated support to those at risk of
      suicide and those bereaved. In 2016, there were up to 300 different groups
      providing support. Clearly, a coordinated, effective and compassionate approach
      is needed, linking community and state resources meaningfully with each other.
      Approaches rooted outside of core mental health services will be vital:
      addressing alcohol problems and other addictions, reducing homelessness,
      reforming the criminal justice system and improving social care.

PMID- 30115200
TI  - From the editor's desk.

PMID- 30115201
TI  - Internet use among young people with and without mental health difficulties.
AB  - OBJECTIVES: Research regarding adolescent internet use and mental health is
      sparse. However, awareness of a young person's internet use is becoming
      increasingly recognised as an important element of clinical assessment and
      intervention, and requires the development of an evidence base. The aim of the
      present study was to better understand the internet use of young people
      experiencing mental health difficulties and to contrast it with those who
      currently report no concerns. METHOD: In total, 299 young people aged 12-19
      years, across a continuum of mental health difficulties, completed an online
      survey measuring internet use and related experiences. Young people were assigned
      to four groups: (a) attending inpatient services; (b) attending outpatient
      services; (c) a community group with mental health concerns and no clinical
      support; and (d) a regular community group. RESULTS: Those in the inpatient and
      outpatient groups visited more potentially harmful websites. Young people
      attending inpatient and outpatient services showed aspects of both more risky and
      less risky use. The community group reporting no mental health difficulties
      showed least risky use. The group experiencing difficulties but not receiving
      support showed consistently high risky use, suggesting this is a particularly
      vulnerable group. CONCLUSIONS: Despite methodological limitations, findings
      suggest that those with mental health difficulties may experience more of the
      risks and fewer of the benefits offered by the internet. Though further research
      is needed to clarify these findings, clinicians should consider routine
      assessment of Internet use when planning interventions for young people
      experiencing mental health difficulties.

PMID- 30115202
TI  - Widening the net: exploring social determinants of burden of informal carers.
AB  - OBJECTIVES: Providing care for a person with dementia or other chronic illness at
      home often places stress on the primary caregiver. In an Irish population, ~67%
      of carers reported experiencing extreme physical or mental tiredness. This study
      aimed to identify factors that influence carer burden and identify the sub
      populations of carers who are most susceptible to burden. METHODS: Consecutive
      carers referred to a local carers' support organisation completed the following
      measurements: the Neuropsychiatric Inventory, Zarit Burden Interview, Social
      Network Index, General Health Questionnaire, Short Form Survey, Hamilton
      Depression Rating Scale, Brown's Locus of Control scale and provided demographic
      data on themselves and their patient. RESULTS: The sample consisted 53 carers,
      mean age: 64.5+/-11.7, of whom 43 (81.1%) were females. A linear regression model
      found significant independent (p<0.05) factors for carer burden were: increased
      behavioural problems of the patient, carer characteristics including female
      gender, younger age, high number of contacts, lower physical functioning and
      emotional problems, while protective factors were marriage and higher number of
      embedded networks. CONCLUSIONS: The ability to predict which carers are more
      susceptible to burden allows service providers to more quickly and accurately
      identify 'higher risk' carers, facilitating routine check-ups by physicians and
      carer support services.

PMID- 30115204
TI  - A dramatic case of a woman discovered after 7 months of untreated catatonia.
AB  - Described is an unusually severe case of catatonia in the context of a major
      depressive episode. The patient is a 49-year-old Caucasian female who was living
      with her husband in an urban apartment. In March 2015, she experienced a major
      depressive episode in the context of financial hardship after being dismissed
      from her job. She became catatonic and did not leave her apartment for 7 months.
      For the first 4 months she lay in bed, then after losing bowel and bladder
      continence, she was transferred by her husband to the bedroom floor where she lay
      prone for another 3 months before paramedics were notified. She subsequently
      underwent a 4-month admission to an intensive care unit, surgical ward, and
      psychiatric ward. This case shows the extreme extent of psychiatric and physical
      sequelae that can result from prolonged delay of treatment of severe catatonia in
      the context of depression.

PMID- 30115203
TI  - The association between childhood trauma, parental bonding and depressive
      symptoms and interpersonal functioning in depression and bipolar disorder.
AB  - OBJECTIVES: This study explores rates of a history of childhood trauma in adult
      patients with bipolar disorder and depression and the impact of such trauma and
      parental bonding patterns on depressive mood and interpersonal functioning at the
      time of assessment. METHODS: A cross-sectional design was used and a sample of 49
      participants was recruited from a mental health outpatient service in Northern
      Ireland. Data were subject to correlations, one-way analysis of variance and
      hierarchal regression analyses. A cut-off point of r=+/-0.25 was used to select
      variables for inclusion in the hierarchal regression analyses. RESULTS: High
      rates of childhood trauma were present in both samples: 74% in bipolar disorder
      and 82% in depression. Childhood trauma and poor parental bonding (with mother)
      were significant predictors of higher rates of current inter-episode depressive
      mood and interpersonal difficulties. CONCLUSIONS: This finding adds to the
      evidence that routine assessment of early childhood experience is likely to prove
      helpful in clinical care.

PMID- 30115205
TI  - Effectiveness of a national 'Minnesota Model' based residential treatment
      programme for alcohol dependence in Ireland: outcomes and predictors of outcome.
AB  - OBJECTIVES: The aims of this study were (a) to examine the effectiveness of an
      inpatient treatment programme for alcohol dependence based on the 'Minnesota
      Model' and (b) to examine potential predictors of outcomes from such treatment.
      METHODS: Demographics and data relating to psychosocial functioning of a group of
      individuals who commenced treatment for alcohol dependence were gathered at the
      point of treatment entry. These individuals were then followed up 6 months after
      they were to complete their inpatient treatment to establish their alcohol
      related outcomes. Outcomes from treatment were identified as an index of
      treatment effectiveness and the outcome data were analysed to determine whether
      any of the baseline variables could be used to predict outcomes from treatment.
      RESULTS: Of those who were contacted at 6-month follow-up, 81.5% had a 'good
      outcome'. This represented 66.7% of the total group who participated in the
      study. The only variable that was found to predict outcomes at 6-month follow-up
      was severity of alcohol dependence at treatment entry, with more severe alcohol
      problems associated with poorer outcomes. CONCLUSIONS: This study provides
      evidence of the potential for a Minnesota-based treatment programme to be
      effective in helping people with alcohol dependence to reduce the amount of
      alcohol they consume and sustain this reduction beyond the treatment period.

PMID- 30115206
TI  - Exploring the impact of adverse childhood experiences on symptomatic and
      functional outcomes in adulthood: advances, limitations and considerations.
AB  - Exposure to traumatic experiences in childhood is a risk (and potentially causal)
      factor for the development of a range of adverse physical and mental health
      conditions. In addition to the onset of clinical disorders, there is emerging
      evidence that childhood trauma may also be associated with other long-term
      outcomes, such as the persistence and severity of an individual's symptoms, as
      well as their long-term social and occupational functioning. However, the reasons
      for this remain poorly understood. A greater understanding both of the mediators
      that drive these associations, and those variables that enhance resilience
      against such damaging experiences may help to inform effective therapeutic
      interventions. In addition to biological and cognitive measures, there is a need
      to consider social and environmental factors, such as parental bonding and
      attachment, when investigating these complex relationships.

PMID- 30115207
TI  - Examining stress: an investigation of stress, mood and exercise in medical
      students.
AB  - OBJECTIVES: Stress is an event that threatens homoeostasis and thus causes
      physiological and behavioural responses to reinstate equilibrium. Excessive
      and/or chronic stress can be psychologically and physiologically detrimental.
      Examinations can represent a significant source of stress for students. The
      hypothalamic-pituitary-adrenal axis (HPA) is the core endocrine stress system.
      Investigations into the HPA response to examinations have yielded inconsistent
      results. The aim of this study is to further explore the relationship between
      examination stress, HPA axis activity, mood, sleep and exercise in students
      undergoing a naturalistic examination period stressor. METHODS: In total, 16
      medical students participated. Students completed self-reported stress, anxiety,
      mood, sleep and physical activity questionnaires, and provided saliva samples
      during an examination-free period and an examination period 1 month later. The
      cortisol awakening response, representative of HPA activity, was determined from
      saliva samples by enzyme-linked immunosorbent assay. RESULTS: Anxiety levels
      increased (p=0.04) and mood decreased (p=0.05) during the examination period.
      There was concomitant decease in physical activity levels (p=0.02). There was no
      significant increase in HPA activity during the examination period (p=0.29).
      Sleep quality did not significantly worsen (p=0.55) during the examination
      period. CONCLUSIONS: Examination periods are associated with increased anxiety
      levels, lower mood and decreased physical activity. Future studies incorporating
      examination results and cognitive function may help to identify potential
      protective interventional strategies, while optimising performance.

PMID- 30115208
TI  - Conceptualizations of suicide through time and socio-economic factors: a
      historical mini-review.
AB  - OBJECTIVES: Suicide is a complex phenomenon determined by the interplay of an
      articulated network of factors including socio-economic factors which have a
      decisive role. This paper investigates the development of the modern
      conceptualization of suicide in Europe, its sociological understandings and its
      intertwinement with economic cycles throughout time. METHODS: MEDLINE, SCHOLAR,
      EMBASE using the keywords 'socioeconomic factors AND suicide'; 'economic cycles
      AND suicide'; 'history AND suicide' without timeframe limitations. Moreover,
      journal-by-journal search in journals of related areas was performed. RESULTS: In
      total, 51 historical studies focusing on the subjects in European countries were
      included. Three main areas arose: (a) development of the conceptualization of
      suicide over time; (b) sociological understandings of suicide according to the
      structure of society and its economy of power; (c) economic theories explaining
      the intertwinement of economic cycles and suicides. CONCLUSIONS: Suicide is a
      deeply human phenomenon inescapably linked to and grounded in society and
      economic cycles. Understandings from the past show the importance of accurate
      analysis of socio-economic contexts that shape societies together with man's own
      sense of self in order to organize multi-layered tangible and intangible support
      strategies to better understand and prevent suicide in this day and age.

PMID- 30115209
TI  - A comprehensive analysis of the factor structure of the Beck Depression Inventory
      II in a sample of outpatients with adjustment disorder and depressive episode.
AB  - OBJECTIVES: Despite being commonly used in research and clinical practice, the
      evidence regarding the factor structure of the Beck Depression Inventory-II (BDI
      II) remains equivocal and this has implications on how the scale scores should be
      aggregated. Researchers continue to debate whether the BDI-II is best viewed as a
      unidimensional scale, or whether specific subscales have utility. The present
      study sought to test a comprehensive range of competing factor analytic models of
      the BDI-II, including traditional non-hierarchical multidimensional models and
      confirmatory bifactor models. METHOD: Participants (n=370) were clinical
      outpatients diagnosed with either depressive episode or adjustment disorder.
      Confirmatory factor analysis and confirmatory bifactor modelling were used to
      test 15 competing models. The unidimensionality of the best fitting model was
      assessed using three strength indices (explained common variance, percentage of
      uncontaminated correlations and omega hierarchical). RESULTS: Overall, bifactor
      solutions provided superior fit than both unidimensional and non-hierarchical
      multidimensional models. The best fitting model consisted of a general depression
      factor and three specific factors: cognitive, somatic and affective. High factor
      loadings and strength indices for the general depression factor supported the
      view that the BDI-II measures a single latent construct. CONCLUSIONS: The BDI-II
      should primarily be viewed as a unidimensional scale, and should be scored as
      such. Although it is not recommended that scores on individual subscales are used
      in isolation, they may prove useful in clinical assessment and/or treatment
      planning if used in conjunction with total scores.

PMID- 30115210
TI  - Polyvagal theory, neurodevelopment and psychiatric disorders.
AB  - Neurodevelopment is an area of psychiatry which has attracted huge interest in
      the last few decades. There is substantial evidence that perinatal events can
      contribute to later development of mental disorder. In the current perspective
      article we propose a novel polyvagal theory which attempts to link prenatal
      events with neurodevelopment and the later onset of psychiatric disorder.

PMID- 30115211
TI  - Young people, the internet and mental health.
AB  - The original research by Mullen et al. in this issue is a welcome contribution to
      the increasingly important research area concerned with mental health and
      internet use. There is a persistent and growing tension between harmful online
      content and the potential to support vulnerable people online. Although current
      research has established both negative and positive influences of the internet on
      mental health, a policy framework to guide the development of online mental
      health resources is lacking. Based on 20 years of online service provision (in
      Australia originally and now in Ireland), ReachOut.com has gained important
      insights into young people's online behaviour and help-seeking preferences. Given
      that young people have expressed concerns about the impact of the internet and
      social media on their mental health, yet they will go online for support, there
      is a clear need for leadership and the resourcing of quality assured, engaging
      online mental health supports. Such an approach will be the most effective way of
      mitigating the threat posed by harmful online content.

PMID- 30115212
TI  - General Practitioners' experience of child and adolescent suicidal ideation and
      behaviour - a survey.
AB  - OBJECTIVES: A major cause of death in Irish men aged 15-24 is suicide and the
      rates for those aged 15-19 are amongst the highest in Europe. Despite concerns
      over suicidal ideation or behaviour, little research has been done in the Irish
      primary care context. We therefore aimed to carry out a study of Irish General
      Practitioners (GPs)' experience regarding suicidal ideation or behaviour in
      children and adolescents. METHODS: The study design was a descriptive, cross
      sectional, questionnaire survey. We randomly selected 480 GPs and invited them to
      participate via post. RESULTS: In total, 198 GPs replied, representing a response
      rate of 41% with a sampling error of +/-6.8%. In total, 184 of respondents (93%)
      saw more than 50 children and adolescent patients annually, however,
      presentations of suicidal ideation and behaviour were relatively rare, with 36%
      reporting seeing none, 58% seeing between one and five and 6% seeing more than
      five such presentations annually. In total, 119 (62%) of GPs reported a
      willingness to prescribe antidepressants for this age group. In total, 66% of GPs
      felt this was either 'always' or 'usually' a difficult patient group to manage,
      and the single most commonly reported difficulty by GPs was access to services
      [n=48 (33%)]. CONCLUSIONS: GPs reported that their management of children and
      adolescents with suicidal ideation or behaviour is often difficult. GPs play a
      key liaison role in the area of child and adolescent mental health, but our
      results indicate that GPs are also involved in the treatment of this patient
      group. However, ongoing education was not a priority according to GPs themselves.

PMID- 30115213
TI  - An intensive personalised support approach to treating individuals with psychosis
      and co-morbid mild intellectual disability.
AB  - OBJECTIVES: To evaluate the clinical benefits and associated cost effectiveness
      of an intensive personalised support (IPS) approach for clients suffering from
      psychosis and co-morbid mild intellectual disability (ID). METHOD: Four
      individuals with a psychotic disorder and co-morbid mild ID participated in an 18
      month IPS rehabilitative intervention. Biopsychosocial measures were used to
      evaluate clinical effectiveness. A cost analysis was undertaken to examine the
      cost effectiveness of the intervention. RESULTS: Reductions in psychopathology
      including anxiety symptoms were noted in all individuals. In addition, increased
      functioning and quality of life were demonstrated in all cases. Overall cost
      reductions were noted in inpatient care, accommodation and legal/emergency
      expenses. CONCLUSION: The IPS approach was clinically effective particularly in
      addressing individual's psychosocial needs, psychological functioning, daily
      living skills and overall quality of life. Costs had decreased for three of the
      four individuals, ranging from a 17% to 46% savings. The findings highlight that
      the intervention was cost effective in most cases at this early stage. However,
      further research is necessary in order to ascertain if cost savings occur over
      time.

PMID- 30115214
TI  - Demographic characteristics of survivors of torture presenting for treatment to a
      national centre for survivors of torture in Ireland (2001-2012).
AB  - OBJECTIVES: The asylum process has received a lot of recent media attention but
      little has been said about the psychological needs of those seeking or granted
      asylum. Many asylum seekers have experienced trauma and torture, which is
      associated with substantial psychiatric and psychological morbidity. The Spiritan
      Asylum Services Initiative (Spirasi) is Ireland's national treatment centre for
      survivors of torture. The aim of this study was to examine the demographic
      profile of those attending Spirasi and to consider potential clinical
      implications of this. METHODS: We retrospectively analysed demographic data
      relating to the 2590 individuals who attended Spirasi over a 12-year period (2001
      2012 inclusive). RESULTS: The majority of attenders were asylum seekers (88%),
      male (71%) and from African countries. The mean age was 31.9 years. The rate of
      new referrals, as a percentage of Ireland's asylum-seeking population, has
      stabilised at ~6% since 2008. Women are underrepresented among those who attend.
      CONCLUSIONS: The number of new referrals to Spirasi is lower than expected given
      international estimates of torture prevalence and the impact this has on mental
      health. Clinicians working with populations of asylum seekers and refugees should
      sensitively enquire about such events and be aware of the available services.
      Female refugees and asylum seekers are underrepresented, especially from Asian
      and Middle Eastern regions. Psychiatric, psychological and general practice
      services need to respond flexibly to evolving patterns of migration and address
      potential barriers to access, especially among female refugees and asylum
      seekers.

PMID- 30115215
TI  - Lipids and polyunsaturated fatty acid levels in deliberate self-harm: a 10-year
      follow-up study.
AB  - OBJECTIVES: To evaluate if n-3 polyunsaturated fatty acids (PUFAs) and lipid
      levels are associated with episodes of self-harm or depression over a 10-year
      period. METHODS: We included 40 individuals who self-harmed and 40 controls.
      Episodes of self-harm and depression were ascertained and levels of depression,
      impulsivity, suicidal ideation and plasma lipid levels measured at baseline and
      at 10-year follow-up. RESULTS: Further episode(s) of self-harm occurred in 26% of
      cases. Omega-3 PUFAs or lipids were not predictive of depressive or self-harm
      episodes. Baseline eicosapentaenoic acid levels were modestly correlated with
      suicidal ideation at follow-up and dihomo-gamma-linolenic acid and arachidonic
      acid were modestly correlated with motor impulsivity at follow-up in cases.
      CONCLUSIONS: Despite significant negative correlations at baseline between plasma
      lipids, n-3 PUFAs and psychopathology, these levels were not predictive of
      clinical outcome over a 10-year period. Further research however is required due
      to the relatively low sample size and the risk of selection bias due to loss to
      follow-up in this study.

PMID- 30115216
TI  - Anthropology and its relevance to psychiatry.

PMID- 30115217
TI  - Letter to the Editor.

PMID- 30115218
TI  - Lithium monitoring patterns in the United Kingdom and Ireland: Can shared care
      agreements play a role in improving monitoring quality? A systematic review.
AB  - BACKGROUND: The appropriate monitoring of patients on lithium therapy has been
      the subject of extensive research in the form of clinical audits and surveys
      culminating in the development of specific guidelines to help clinicians provide
      optimal care for patients on lithium. The concept of 'shared care' has also
      gained attention in the literature with various types of shared care
      interventions being introduced as potential ways of improving communication
      between primary and secondary care. OBJECTIVES: This article aims to (1) review
      the literature evaluating lithium monitoring practices in the United Kingdom and
      Ireland in the last 25 years and (2) determine whether locally agreed shared care
      agreements have the potential to improve monitoring quality. METHODS: A
      literature search was conducted using the following databases: PubMed, Scopus,
      Web of Science, Academic Search Premier, CINAHL and PsychInfo. A total of 12
      studies were selected for review including 11 audits/prospective chart reviews
      and one qualitative study using semi-structured interviews. CONCLUSIONS: Overall,
      the quality of lithium monitoring seems to be improving throughout the years.
      However, none of the studies reviewed revealed complete adherence to monitoring
      guidelines. This may be due to a lack of effective communication between primary
      and secondary care. Several shared care interventions have been described in the
      literature but there is a paucity of studies concerned with the effects of local
      shared care arrangements designed for the specific purpose of lithium monitoring.
      Nonetheless, the extant data suggests that such agreements may help improve
      monitoring standards by allowing the responsibilities for managing the
      prescribing and monitoring of lithium to be more clearly defined and shared
      between primary and secondary care.

PMID- 30115219
TI  - Improving fluoroquinolone use in the outpatient setting using a patient safety
      initiative.
AB  - We analyzed the impact of a fluoroquinolone patient safety initiative on the
      weekly fluoroquinolone prescription rate in Veterans Affairs community-based
      outpatient clinics. We observed a significant initial but unsustained reduction.
      Such an initiative can function as an antimicrobial stewardship intervention;
      however, strategies to promote sustainability should be explored.

PMID- 30115220
TI  - Myocardial Fibrosis in Patients With Primary Mitral Regurgitation With and
      Without Prolapse.
AB  - BACKGROUND: Recent studies reported left ventricular (LV) fibrosis in patients
      with primary mitral regurgitation (MR) thought to be principally due to mitral
      valve prolapse (MVP). OBJECTIVES: This study sought to evaluate the prevalence,
      characteristics, and prognostic implications of LV fibrosis in a large cohort of
      primary MR patients with and without MVP using cardiovascular magnetic resonance
      (CMR). METHODS: Patients referred for contrast CMR assessment of chronic primary
      MR were enrolled and underwent comprehensive assessment of cardiac remodeling,
      severity of MR, and LV replacement fibrosis. Primary MR patients were stratified
      into: an MVP group if there was >2 mm mitral leaflet displacement on cine-CMR, or
      a non-MVP group. Patients were followed for arrhythmic events (sudden cardiac
      death, aborted sudden cardiac arrest, and sustained or inducible ventricular
      arrhythmia). RESULTS: A total of 356 primary MR patients (177 MVP and 179 non
      MVP) were enrolled. LV fibrosis was more prevalent in the MVP group than the non
      MVP group (36.7% vs. 6.7%; p < 0.001). The presence of MVP had the strongest
      association (odds ratio: 6.82; p < 0.001) with LV fibrosis even after adjustment
      for clinical variables, measures of cardiac remodeling, and MR severity. During
      follow-up (median 1,354 days), MVP patients with LV fibrosis had the highest
      event rate for arrhythmic events. CONCLUSIONS: In primary MR patients, LV
      fibrosis is more prevalent in MVP than non-MVP, suggesting a unique
      pathophysiology beyond volume overload in MVP. LV fibrosis in primary MR may
      represent a risk marker of arrhythmic events.

PMID- 30115221
TI  - Mitral Valve Prolapse: A Disease of Valve and Ventricle.

PMID- 30115222
TI  - Edoxaban in Asian Patients With Atrial Fibrillation: Effectiveness and Safety.
AB  - BACKGROUND: It is unclear whether edoxaban shows better risk reduction of
      ischemic stroke, bleeding, and all-cause mortality than warfarin in Asian
      patients with nonvalvular atrial fibrillation (AF). OBJECTIVES: This study
      compared the effectiveness and safety of edoxaban with those of warfarin in a
      Korean population with AF. METHODS: Using the Korean National Health Insurance
      Service database, we included new users of edoxaban and warfarin in patients with
      AF from January 2014 to December 2016 (n = 4,200 on edoxaban, and n = 31,565 on
      warfarin) and analyzed the risk of ischemic stroke, intracranial hemorrhage
      (ICH), hospitalization for gastrointestinal (GI) bleeding, hospitalization for
      major bleeding, and all-cause death. The propensity score matching method was
      used to balance covariates across edoxaban and warfarin users. RESULTS: We
      compared a 1:3 propensity score-matched cohort of patients with AF who were new
      users of edoxaban and warfarin (n = 4,061 and n = 12,183, respectively). Baseline
      characteristics were balanced between the 2 groups (median age 72 years; median
      CHA2DS2-VASc [congestive heart failure, hypertension, age >=75 years, diabetes
      mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular
      disease, age 65-74 years, sex category (female)] score 3). Edoxaban users had a
      significantly lower risk of ischemic stroke (hazard ratio [HR]: 0.693; 95%
      confidence interval [CI]: 0.487 to 0.959), ICH (HR: 0.407; 95% CI: 0.182 to
      0.785), hospitalization for GI bleeding (HR: 0.597; 95% CI: 0.363 to 0.930),
      hospitalization for major bleeding (HR: 0.532; 95% CI: 0.352 to 0.773), and all
      cause death (HR: 0.716; 95% CI: 0.549 to 0.918) than warfarin users. All
      subgroups (age, sex, CHA2DS2-VASc score, renal function, edoxaban dose) showed
      better clinical outcomes with edoxaban than with warfarin. CONCLUSIONS: In this
      real-world Asian population with AF, edoxaban might be associated with reduced
      risk of ischemic stroke, major bleeding, and all-cause death compared with
      warfarin. These benefits were consistent across various high-risk subgroups.

PMID- 30115223
TI  - Edoxaban's Journey: From East Asia to the Globe, Back to East Asia.

PMID- 30115224
TI  - Late Gadolinium Enhancement in Patients With Hypertrophic Cardiomyopathy and
      Preserved Systolic Function.
AB  - BACKGROUND: A high proportion of patients with hypertrophic cardiomyopathy (HCM)
      have evidence of late gadolinium enhancement (LGE) on cardiac magnetic resonance
      (CMR). OBJECTIVES: This study sought to assess the incremental prognostic utility
      of LGE in patients with HCM. METHODS: We studied 1,423 consecutive low
      /intermediate-risk patients with HCM (age >=18 years) with preserved left
      ventricular (LV) ejection fraction (mean age 66 +/- 14 years, 60% men) who
      underwent transthoracic echocardiography (TTE) (including dimensions and LV
      outflow tract gradients) and CMR (including LGE as a % of LV mass) at our center
      between January 2008 and December 2015. The primary composite endpoint was sudden
      cardiac death (SCD) and appropriate implantable cardioverter-defibrillator
      discharge. The percent 5-year SCD risk score was calculated. RESULTS: The mean 5
      year SCD risk score was 2.3 +/- 2.0. Mean maximal LV outflow tract gradient (TTE)
      was 70 +/- 55 mm Hg (median 74 mm Hg [interquartile range (IQR): 10 to 67 mm
      Hg]); indexed LV mass and LGE (both on CMR) were 91 +/- 10 g/m2 and 8.4 +/- 12%
      (IQR: 0% to 19%); 50% had LGE on CMR. Of these, 458 were nonobstructive and 965
      were obstructive (of which 686 were underwent myectomy). At 4.7 +/- 2.0 years of
      follow-up, 60 (4%) met the composite endpoint. On quadratic spline analysis, LGE
      >=15% was associated with increased risk of composite events. In the obstructive
      subgroup, on competing risk regression analysis, >=15% LGE (subhazard ratio: 3.04
      [95% confidence interval: 1.48 to 6.10]) was associated with a higher rate and
      myectomy (subhazard ratio: 0.44 [95% confidence interval: 0.20 to 0.76]) was
      associated with a lower rate of composite endpoints (both p < 0.01). Similarly,
      sequential addition of LGE >=15% and myectomy to % 5-year SCD risk score improved
      the log likelihood ratios from -227.85 to -219.14 (chi-square 17) and to -215.14
      (chi-square 8; both p < 0.01). Association of %LGE with composite events was
      similar even in myectomy and nonobstructive subgroups. CONCLUSIONS: In low
      /intermediate-risk adult patients with HCM (obstructive, myectomy, and
      nonobstructive subgroups) with preserved systolic function, %LGE was
      significantly associated with a higher rate of composite endpoint, providing
      incremental prognostic utility.

PMID- 30115225
TI  - Further Refining Risk in Hypertrophic Cardiomyopathy With Late Gadolinium
      Enhancement by CMR.

PMID- 30115227
TI  - Survival After Takotsubo, Revisited.

PMID- 30115229
TI  - Manipulating Macrophage Polarization to Fix the Broken Heart: Challenges and
      Hopes.

PMID- 30115230
TI  - Cardiovascular Health Promotion: An Issue That Can No Longer Wait.

PMID- 30115226
TI  - Long-Term Prognosis of Patients With Takotsubo Syndrome.
AB  - BACKGROUND: Prognosis of Takotsubo syndrome (TTS) remains controversial due to
      scarcity of available data. Additionally, the effect of the triggering factors
      remains elusive. OBJECTIVES: This study compared prognosis between TTS and acute
      coronary syndrome (ACS) patients and investigated short- and long-term outcomes
      in TTS based on different triggers. METHODS: Patients with TTS were enrolled from
      the International Takotsubo Registry. Long-term mortality of patients with TTS
      was compared to an age- and sex-matched cohort of patients with ACS. In addition,
      short- and long-term outcomes were compared between different groups according to
      triggering conditions. RESULTS: Overall, TTS patients had a comparable long-term
      mortality risk with ACS patients. Of 1,613 TTS patients, an emotional trigger was
      detected in 485 patients (30%). Of 630 patients (39%) related to physical
      triggers, 98 patients (6%) had acute neurologic disorders, while in the other 532
      patients (33%), physical activities, medical conditions, or procedures were the
      triggering conditions. The remaining 498 patients (31%) had no identifiable
      trigger. TTS patients related to physical stress showed higher mortality rates
      than ACS patients during long-term follow-up, whereas patients related to
      emotional stress had better outcomes compared with ACS patients. CONCLUSIONS:
      Overall, TTS patients had long-term outcomes comparable to age- and sex-matched
      ACS patients. Also, we demonstrated that TTS can either be benign or a life
      threating condition depending on the inciting stress factor. We propose a new
      classification based on triggers, which can serve as a clinical tool to predict
      short- and long-term outcomes of TTS. (International Takotsubo Registry [InterTAK
      Registry]; NCT01947621).

PMID- 30115228
TI  - Deficiency of GATA3-Positive Macrophages Improves Cardiac Function Following
      Myocardial Infarction or Pressure Overload Hypertrophy.
AB  - BACKGROUND: Macrophages are highly plastic cells that play an important role in
      the pathogenesis of cardiovascular disease. OBJECTIVES: This study investigated
      the role of GATA3-positive macrophages in modulating cardiac function after
      myocardial infarction (MI) or in response to pressure overload hypertrophy.
      METHODS: Myeloid-specific GATA3-deficient (mGATA3KO) mice were generated, MI or
      pressure overload was induced, and cardiac function was determined by
      echocardiography. GATA3-sufficient Cre mice were used as a control.
      Immunohistochemical staining, flow cytometry, MILLIPLEX Mouse Cytokine/Chemokine
      Assay, cultured macrophages, quantitative real-time polymerase chain reaction,
      and western blot were used to determine the role of GATA3 in macrophages.
      RESULTS: GATA3-positive macrophages rapidly accumulated in the infarcted region
      of the myocardium after acute MI. Deficiency of GATA3-positive macrophages led to
      a significant improvement of cardiac function in response to acute MI or pressure
      overload hypertrophy compared with the control mice. This improvement was
      associated with the presence of a large number of proinflammatory Ly6Chi
      monocytes/macrophages and fewer reparative Ly6Clo macrophages in the myocardium
      of mGATA3KO mice compared with control mice. Analysis of serum proteins from the
      2 mouse genotypes revealed no major changes in the profile of serum growth
      factors and cytokines between the 2 mice genotypes before and after MI. GATA3 was
      found to be specifically and transiently induced by interleukin 4 in cultured
      macrophages through activity of the proximal promoter, whereas the distal
      promoter remained silent. In addition, the absence of GATA3 in macrophages
      markedly attenuated arginase-1 expression in cultured macrophages. CONCLUSIONS:
      We demonstrated that the presence of GATA3-positive macrophages adversely affects
      remodeling of the myocardium in response to ischemia or pressure overload,
      whereas the absence of these macrophages led to a significant improvement in
      cardiac function. Targeting of signaling pathways that lead to the expression of
      GATA3 in macrophages may have favorable cardiac outcomes.

PMID- 30115233
TI  - It Takes a Team to Deliver Optimal Cardiovascular Care.

PMID- 30115232
TI  - His Bundle Pacing.
AB  - Traditional right ventricular (RV) pacing for the management of bradyarrhythmias
      has been pursued successfully for decades, although there remains debate
      regarding optimal pacing site with respect to both hemodynamic and clinical
      outcomes. The deleterious effects of long-term RV apical pacing have been well
      recognized. This has generated interest in approaches providing more
      physiological stimulation, namely, His bundle pacing (HBP). This paper reviews
      the anatomy of the His bundle, early clinical observations, and current
      approaches to permanent HBP. By stimulating the His-Purkinje network, HBP engages
      electrical activation of both ventricles and may avoid marked dyssynchrony.
      Recent studies have also demonstrated the potential of HBP in patients with
      underlying left bundle branch block and cardiomyopathy. HBP holds promise as an
      attractive mode to achieve physiological pacing. Widespread adaptation of this
      technique is dependent on enhancements in technology, as well as further
      validation of efficacy in large randomized clinical trials.

PMID- 30115234
TI  - Correlation of Altmetric Attention Score With Article Citations in Cardiovascular
      Research.

PMID- 30115235
TI  - Omega-3 Fatty Acids Effect on Post-Myocardial Infarction ST2 Levels for Heart
      Failure and Myocardial Fibrosis.

PMID- 30115236
TI  - Infection-Induced Humoral Autoimmunity: A Missing Link in the Interplay Between
      Pathogens, Dyslipidemia, and Innate Immunity?

PMID- 30115237
TI  - Patient-Specific Computer Modeling for the Planning of Transcatheter Mitral Valve
      Replacement.

PMID- 30115238
TI  - Reply: Infection and Atherogenesis.

PMID- 30115239
TI  - Reply: Patient-Specific Computer Modeling for the Planning of Transcatheter
      Mitral Valve Replacement.

PMID- 30115231
TI  - Cardiovascular Disease Prevention by Diet Modification: JACC Health Promotion
      Series.
AB  - Reduction in excess calories and improvement in dietary composition may prevent
      many primary and secondary cardiovascular events. Current guidelines recommend
      diets high in fruits, vegetables, whole grains, nuts, and legumes; moderate in
      low-fat dairy and seafood; and low in processed meats, sugar-sweetened beverages,
      refined grains, and sodium. Supplementation can be useful for some people but
      cannot replace a good diet. Factors that influence individuals to consume a low
      quality diet are myriad and include lack of knowledge, lack of availability, high
      cost, time scarcity, social and cultural norms, marketing of poor-quality foods,
      and palatability. Governments should focus on cardiovascular disease as a global
      threat and enact policies that will reach all levels of society and create a food
      environment wherein healthy foods are accessible, affordable, and desirable.
      Health professionals should be proficient in basic nutritional knowledge to
      promote a sustainable pattern of healthful eating for cardiovascular disease
      prevention for both healthy individuals and those at higher risk.

PMID- 30115240
TI  - Evolving Perspectives on the Public Health Burden of Eating Disorders.

PMID- 30115241
TI  - Stereotactic Radiosurgical Capsulotomy for the Treatment of Refractory Obsessive
      Compulsive Disorder.

PMID- 30115242
TI  - Distinct but Synergistic Roles for Histone Deacetylase in the Dorsal Striatum
      During Habit Formation.

PMID- 30115243
TI  - Poverty, Parenting, and Psychiatry.

PMID- 30115244
TI  - A Developmental Perspective of Dopaminergic Dysfunction in Tourette Syndrome.

PMID- 30115245
TI  - Machine learning and evidence-based training in technical skills.

PMID- 30115246
TI  - Near-infrared spectroscopy: unfulfilled promises.

PMID- 30115247
TI  - Can you hear me now? Information processing in primary auditory cortex at loss of
      consciousness.

PMID- 30115248
TI  - Back to the future: lifelong changes in pain processing in 'ageing of
      prematurity'.

PMID- 30115249
TI  - Dr J. Edmund Riding CBE, MD, FRCA, FRCS (Hon), FCARCSI (Hon), FANZCA (Hon): 1924
      2018.

PMID- 30115250
TI  - Dynamic arterial elastance measured by uncalibrated pulse contour analysis
      predicts arterial-pressure response to a decrease in norepinephrine.
AB  - BACKGROUND: Dynamic arterial elastance (Eadyn) has been proposed as an indicator
      of vascular tone that predicts the decrease in arterial pressure in response to
      changes in norepinephrine (NE). The purpose of this study was to determine
      whether Eadyn measured by uncalibrated pulse contour analysis (UPCA) can predict
      a decrease in arterial pressure when the NE dosage is decreased. METHODS: We
      conducted a prospective study in a university hospital intensive care unit.
      Patients with vasoplegic syndrome for whom the intensive care physician planned
      to decrease the NE dosage were included. Haemodynamic and UPCA (VolumeView and
      FloTrac; Edwards Lifesciences, Irvine, CA, USA) values were obtained before and
      after decreasing the NE dosage. Responders were defined by a >10% decrease in
      mean arterial pressure (MAP). RESULTS: Of 35 patients included, 11 (31%) were
      pressure responders with a median decrease of 13%. Eadyn was correlated to
      systolic arterial pressure (SAP) (r=0.255; P=0.033), diastolic arterial pressure
      (r=0.271; P=0.024), MAP (r=0.310; P=0.009), heart rate (r=0.543; P=0.0001), and
      transthoracic echography cardiac output (r=0.264; P=0.024). Baseline Eadyn was
      correlated with MAP changes (r=0.394; P=0.019) and SAP changes (r=0.431;
      P=0.009). Eadyn predicted the decrease in arterial pressure with an area under
      the receiver-operating-characteristic curve of 0.84 (95% confidence interval:
      0.70-0.97). The best cut-off was 0.90. CONCLUSIONS: The present study confirms
      the ability of Eadyn measured by UPCA to predict an arterial pressure response to
      a decrease in NE. Eadyn may constitute an easy-to-use functional approach to
      arterial tone assessment regardless of the monitor used to measure its
      determinant. CLINICAL TRIAL REGISTRATION: DRCIT95.

PMID- 30115251
TI  - Carotid ultrasound measurements for assessing fluid responsiveness in
      spontaneously breathing patients: corrected flow time and respirophasic variation
      in blood flow peak velocity.
AB  - BACKGROUND: This study evaluated the ability of two Doppler ultrasound-derived
      parameters, the carotid corrected flow time (FTc) and respirophasic variation in
      carotid artery blood flow peak velocity (DeltaVpeak), to predict fluid
      responsiveness in spontaneously breathing patients. METHODS: A total of 53
      spontaneously breathing patients were studied before anaesthetic induction for
      neurosurgery. Carotid FTc, DeltaVpeak, and haemodynamic data were measured before
      and after administration of 6 ml kg-1 colloid. Fluid responsiveness was defined
      as a 15% or more increase in stroke volume index as assessed by transthoracic
      echocardiography after the fluid challenge. RESULTS: Twenty-two (42%) patients
      were fluid responders. The areas under the receiver operating characteristic
      curves for FTc and DeltaVpeak were 0.842 [95% confidence interval (CI) 0.735
      0.948, P<0.001] and 0.818 (95% CI: 0.701-0.935, P<0.001), respectively. The
      optimal cut-off values of FTc and DeltaVpeak for fluid responsiveness were 349.4
      ms (sensitivity of 72.7%; specificity of 83.9%) and 9.1% (sensitivity of 72.7%;
      specificity of 87.1%), respectively. The grey zone for FTc was 346.9-361.0 ms and
      included 28% of the patients, and the grey zone for DeltaVpeak was 6.5-10.2% and
      included 50% of the patients. CONCLUSIONS: Using Doppler ultrasound-derived
      parameters measured at the carotid artery, FTc predicted fluid responsiveness in
      spontaneously breathing patients better than DeltaVpeak. However, further studies
      are warranted before these parameters are recommended for clinical use. CLINICAL
      TRIAL REGISTRATION: NCT 02843477.

PMID- 30115252
TI  - Validation of capnodynamic determination of cardiac output by measuring effective
      pulmonary blood flow: a study in anaesthetised children and piglets.
AB  - BACKGROUND: Effective pulmonary blood flow (COEPBF) has recently been validated
      as a technique for determining cardiac output (CO) in animals of varying sizes.
      The primary aim of our study was to investigate this new technique in paediatric
      surgical patients, compared with suprasternal two-dimensional Doppler (COSSD).
      METHODS: A total of 15 children undergoing cleft lip/palate surgery were
      investigated. Before the start of surgery, manoeuvres that were anticipated to
      reduce (increase in PEEP from 3 to 10 cm H2O) and increase (atropine) CO were
      undertaken. A study in mechanically ventilated piglets was also undertaken under
      general anaesthesia, measuring COEPBF and pulmonary artery (COTS) flow by
      ultrasonic probe as the comparator. Bias (Bland-Altman plots) and limits of
      agreement were assessed for effective pulmonary blood flow and COSSD or COTS.
      RESULTS: In paediatric patients (median age 8.5 months), overall bias was -8.1
      (limits of agreement -82 to +66) ml kg-1 min-1, with a mean percentage error of
      48% and a concordance rate of 64%. In the piglet model, overall bias was -1 (-36
      to +38) ml kg-1 min-1, with a mean percentage error of 31% and a concordance rate
      of 95%. CONCLUSIONS: Under controlled experimental conditions, COEPBF is
      associated with excellent agreement and good trending ability when compared with
      the gold standard COTS. In the paediatric clinical setting, COEPBF performs well;
      by contrast, COSSD, an operator- and anatomy-dependent technology, appears less
      reliable than COEPBF.

PMID- 30115253
TI  - Population pharmacokinetic analysis of propofol in underweight patients under
      general anaesthesia.
AB  - BACKGROUND: The modified Marsh and Schnider pharmacokinetic models for propofol
      consistently produce negatively and positively biased predictions in underweight
      patients, respectively. We aimed to develop a new pharmacokinetic model of
      propofol in underweight patients. METHODS: Twenty underweight (BMI<18.5 kg m-2)
      patients aged 20-68 yr were given an i.v. bolus of propofol (2 mg kg-1) for
      induction of anaesthesia. Anaesthesia was maintained with a zero-order infusion
      (8 mg kg-1 h-1) of propofol and target-controlled infusion of remifentanil.
      Arterial blood was sampled at preset intervals. A population pharmacokinetic
      analysis was performed using non-linear mixed effects modelling. The time to peak
      effect (tpeak, maximally reduced bispectral index) was measured in 28 additional
      underweight patients receiving propofol 2 mg kg-1. RESULTS: In total, 455 plasma
      concentration measurements from the 20 patients were used to characterise the
      pharmacokinetics of propofol. A three-compartment mammillary model well described
      the propofol concentration time course. BMI and lean body mass (LBM) calculated
      using the Janmahasatian formula were significant covariates for the rapid
      peripheral volume of distribution and for the clearance of the final
      pharmacokinetic model of propofol, respectively. The parameter estimates were as
      follows: V1(L)=2.02, V2(L)=12.9(BMI/18.5), V3(L)=139, Cl (L?min-1)=1.66(LBM/40),
      Q1 (L?min-1)=1.44, Q2 (L?min-1)=0.87+0.0189*(LBM-40). The median tpeak of
      propofol was 1.32 min (n=48). CONCLUSIONS: A three-compartment mammillary model
      can be used to administer propofol via target effect-site concentration
      controlled infusion of propofol in underweight patients. CLINICAL TRIAL
      REGISTRATION: KCT0001760.

PMID- 30115254
TI  - Estimating the rapid haemodynamic effects of passive leg raising in critically
      ill patients using bioreactance.
AB  - BACKGROUND: Rapid detection of changes in cardiac index (CI) in real time using
      minimally invasive monitors may be of clinical benefit. We tested whether the
      Starling-SV bioreactance device, which averages CI over a short 8 s period, could
      assess the effects of passive leg raising (PLR), a clinical test that is
      recommended to assess fluid responsiveness during septic shock. METHODS: In 32
      critically ill patients, we measured CI by transpulmonary thermodilution (PiCCO2,
      CItd), pulse contour analysis (PiCCO2, CIPulse), and the Starling-SV device
      (CIStarling) at baseline. CIPulse and CIStarling were measured again at the end
      of a PLR test. In the 13 patients with a positive PLR test, CItd, CIPulse, and
      CIStarling were measured before and after a 500 ml saline infusion. The primary
      outcome was relative changes from baseline measurements in CItd, CIPulse, and
      CIStarling. Secondary outcomes compared absolute values measured by each method.
      RESULTS: Relative changes in CIPulse and CItd were significantly correlated
      (r=0.82; n=45; P<0.001), with an 89% concordance rate (n=45 paired measurements).
      Relative changes in CIStarling and CItd were also significantly correlated
      (r=0.59; n=45; P<0.001) with a 78% concordance rate. For absolute measures of CI
      (n=77 paired measurements), the bias between CIPulse and CItd was 0.01 L min-1 m
      2 (limits of agreement, -0.49 and 0.51 L min-1 m-2; 15% percentage error). Bias
      between CIStarling and CItd was 0.03 L min-1 m-2 (limits of agreement, -1.61 and
      1.67 L min-1 m-2; 48% percentage error). CONCLUSIONS: In critically ill patients,
      a non-invasive bioreactance device with a shorter averaging period assessed a
      passive leg raising test with reasonable accuracy.

PMID- 30115255
TI  - Volume kinetics of Ringer's lactate solution in acute inflammatory disease.
AB  - BACKGROUND: Little is known about the turnover of crystalloid fluids infused in
      patients with acute systemic inflammation. We hypothesised that systemic
      inflammation would be associated with altered distribution and elimination of
      Ringer's lactate solution (volume kinetics). METHODS: Ringer's lactate solution
      (15 ml kg-1) was infused intravenously over 35 min in patients undergoing
      cholecystectomy (n=20) or appendectomy (n=20) starting before induction of
      general anaesthesia. Blood samples and urine were collected over the following 2
      h. Plasma concentrations of inflammatory (tumour necrosis factor-alpha,
      interleukin-10, and C-reactive protein) and endothelial damage (syndecan-1)
      biomarkers were quantified by enzyme-linked immunosorbent assay. The volume
      kinetics was studied using mixed-effect modelling. RESULTS: Ongoing surgery
      (duration: 30-45 min) increased the rate constant for fluid transfer from the
      plasma to the extravascular space (k12; from 32 to 57*10-3 min-1; P<0.001), and
      decreased the elimination rate constant (k10; from 5.3 to 0.6*10-3 min-1;
      P<0.001). A lower mean arterial pressure was associated with reduced elimination,
      independent of conscious/anaesthetised state. The redistribution of fluid back to
      the plasma occurred more slowly in the group with appendicitis (P<0.02), in whom
      higher plasma concentrations of C-reactive protein were measured [median: 38.1
      (range 1.8-143.6) vs 1.3 (0.1-159.0) MUg ml-1; P<0.001]. However, no biomarkers
      for inflammation or endothelial damage were significantly associated covariates
      in the kinetic model. CONCLUSIONS: No association was found between the volume
      kinetics of Ringer's lactate solution and the degree of inflammation as indicated
      by established biomarkers in patients with cholecystitis or appendicitis.
      However, the rate of elimination was greatly retarded by general anaesthesia in
      both groups. CLINICAL TRIAL REGISTRATION: ChiCTR-IOR-15006063.

PMID- 30115256
TI  - Effects of resuscitation with human albumin 5%, hydroxyethyl starch 130/0.4 6%,
      or crystalloid on kidney damage in an ovine model of septic shock.
AB  - BACKGROUND: Colloid solutions have been associated with kidney dysfunction in
      septic animals and humans. The present study investigated the influence of
      resuscitation with human albumin (HA) 5%, hydroxyethyl starch (HES) 130/0.4 6%,
      and balanced crystalloids on ultrastructural kidney damage, kidney function, and
      survival in a model of ovine septic shock. METHODS: After induction of peritoneal
      septic shock, animals were randomised to one of the following groups: (1) HA 5%,
      (2) HES 130/0.4 6%, (3) balanced crystalloid, and (4) control (each n=10). Causal
      therapy included re-laparotomy, peritoneal lavage, and antimicrobial therapy.
      Sequential kidney biopsies were obtained for the assessment of the electron
      microscopic tubular injury (EMTI) score. RESULTS: Serum creatinine and urea were
      highest in the control group, and there were no differences between the
      intervention groups. Cumulative diuresis was significantly higher in the HA group
      [1.0 ml kg-1 h-1 (0.6; 1.2)] compared with control [0.7 ml kg-1 h-1 (0.6; 0.9),
      P<0.05]. Creatinine clearance was highest in the HA and crystalloid groups.
      Ultrastructural kidney damage was highest in the control group [EMTI score 7.8
      (6.7; 9.0)] without differences between intervention groups. Survival was 100% in
      the colloid groups vs 90% (crystalloid) and 60% (control, all P<0.05).
      CONCLUSION: In an ovine model of septic shock, kidney function and cumulative
      diuresis were preserved in the 5% albumin and crystalloid resuscitation groups,
      whereas HES 130/0.4 6% resulted in diminished creatinine clearance. Differences
      in kidney function between resuscitation fluids could not be explained by
      differences in ultrastructural kidney damage. CLINICAL TRIAL REGISTRATION: 84
      02.04.2011.A300.

PMID- 30115257
TI  - Ultrasound-tagged near-infrared spectroscopy does not disclose absent cerebral
      circulation in brain-dead adults.
AB  - BACKGROUND: Near-infrared spectroscopy, a non-invasive technique for monitoring
      cerebral oxygenation, is widely used, but its accuracy is questioned because of
      the possibility of extra-cranial contamination. Ultrasound-tagged near-infrared
      spectroscopy (UT-NIRS) has been proposed as an improvement over previous methods.
      We investigated UT-NIRS in healthy volunteers and in brain-dead patients.
      METHODS: We studied 20 healthy volunteers and 20 brain-dead patients with two UT
      NIRS devices, CerOxTM and c-FLOWTM (Ornim Medical, Kfar Saba, Israel), which
      measure cerebral flow index (CFI), a parameter related to changes in cerebral
      blood flow (CBF). Monitoring started after the patients had been declared brain
      dead for a median of 34 (range: 11-300) min. In 11 cases, we obtained further
      demonstration of absent CBF. RESULTS: In healthy volunteers, CFI was markedly
      different in the two hemispheres in the same subject, with wide variability
      amongst subjects. In brain-dead patients (median age: 64 yr old, 45% female; 20%
      traumatic brain injury, 40% subarachnoid haemorrhage, and 40% intracranial
      haemorrhage), the median (inter-quartile range) CFI was 41 (36-47), significantly
      higher than in volunteers (33; 27-36). CONCLUSIONS: In brain-dead patients, where
      CBF is absent, the UT-NIRS findings can indicate an apparently perfused brain.
      This might reflect an insufficient separation of signals from extra-cranial
      structures from a genuine appraisal of cerebral perfusion. For non-invasive
      assessment of CBF-related parameters, the near-infrared spectroscopy still needs
      substantial improvement.

PMID- 30115258
TI  - Propofol compared with sevoflurane general anaesthesia is associated with
      decreased delayed neurocognitive recovery in older adults.
AB  - BACKGROUND: The choice of general anaesthetics may affect postoperative cognitive
      outcomes. This study was designed to compare the potential impact of propofol
      based vs sevoflurane-based general anaesthesia on the development of delayed
      neurocognitive recovery in older adults early after major cancer surgery.
      METHODS: Older adults (aged >=65 and <90 yr) who were scheduled to undergo major
      cancer surgery (>=2 h) were randomised to receive either propofol- or sevoflurane
      based general anaesthesia. Cognitive function was assessed before and 1 week
      after surgery with a battery of neuropsychological tests. Age- and education
      matched non-surgical controls were recruited, and their cognitive functions were
      tested at comparable time intervals in order to adjust for learning effects from
      repeated tests. Delayed neurocognitive recovery was diagnosed according to the
      International Study of Postoperative Cognitive Dysfunction 1 definition. RESULTS:
      From April 1, 2015 to October 15, 2016, 392 patients were enrolled and
      randomised. Of these patients, 387 completed the intervention and 30-day follow
      up, and 379 completed 1-week neuropsychological tests. Fifty-nine control
      subjects were enrolled and completed repeated neuropsychological tests. The
      incidence of delayed neurocognitive recovery at 1 week was significantly lower in
      the propofol group [14.8% (28/189)] than in the sevoflurane group [23.2%
      (44/190); odds ratio=0.577; 95% confidence interval, 0.342-0.975; P=0.038].
      Safety outcomes did not differ between the two groups. CONCLUSIONS: When compared
      with sevoflurane-based general anaesthesia, propofol-based general anaesthesia
      might decrease the incidence of delayed neurocognitive recovery in older adults
      after major cancer surgery. CLINICAL TRIALS REGISTRATION: NCT02662257; Chinese
      Clinical Trial Registry (identifier: ChiCTR-IPR-15006209).

PMID- 30115259
TI  - Altered stimulus representation in rat auditory cortex is not causal for loss of
      consciousness under general anaesthesia.
AB  - BACKGROUND: Current concepts suggest that impaired representation of information
      in cortical networks contributes to loss of consciousness under anaesthesia. We
      tested this idea in rat auditory cortex using information theory analysis of
      multiunit responses recorded under three anaesthetic agents with different
      molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if
      changes in the representation of sensory stimuli are causal for loss of
      consciousness, they should occur regardless of the specific anaesthetic agent.
      METHODS: Spiking responses were recorded with chronically implanted microwire
      arrays in response to acoustic stimuli incorporating varied temporal and spectral
      dynamics. Experiments consisted of four drug conditions: awake (pre-drug),
      sedation (i.e. intact righting reflex), loss of consciousness (a dose just
      sufficient to cause loss of righting reflex), and recovery. Measures of firing
      rate, spike timing, and mutual information were analysed as a function of drug
      condition. RESULTS: All three drugs decreased spontaneous and evoked spiking
      activity and modulated spike timing. However, changes in mutual information were
      inconsistent with altered stimulus representation being causal for loss of
      consciousness. First, direction of change in mutual information was agent
      specific, increasing under dexmedetomidine and decreasing under isoflurane and
      propofol. Second, mutual information did not decrease at the transition between
      sedation and LOC for any agent. Changes in mutual information under anaesthesia
      correlated strongly with changes in precision and reliability of spike timing,
      consistent with the importance of temporal stimulus features in driving auditory
      cortical activity. CONCLUSIONS: The primary sensory cortex is not the locus for
      changes in representation of information causal for loss of consciousness under
      anaesthesia.

PMID- 30115260
TI  - Usefulness of the pain sensitivity questionnaire to discriminate the pain
      behaviour of chronic pain patients.
AB  - BACKGROUND: Chronic pain is no longer an effective warning system, but a syndrome
      with co-morbidities and many causes, needing a careful evaluation. Questions
      remain about the pain behaviour of chronic pain patients compared with patients
      with acute pain, or healthy subjects that we investigated. METHODS: We compared
      three populations: healthy (HS, n=280), with acute pain (AP=110 patients), and
      chronic pain (CP=280 patients) by assessing their pain behaviour with the pain
      sensitivity questionnaire (PSQ-total and PSQ-minor). The influence of central
      sensitisation syndrome (CSS) on chronic pain behaviour, including
      catastrophising, was further investigated by using the central sensitisation
      inventory. RESULTS: Compared with the AP patients and HS, the CP patients
      exhibited significantly higher catastrophising scores; higher PSQ-minor scores
      [29.0 (21.0-39.0), than for AP 24.0 (14.0-32.5), and for healthy subjects 25.0
      (17.0-34.0); and PSQ-total scores of for CP, 63.5 for AP, and 64.0 for HS. No
      significant difference was observed between the HS and AP populations.
      Significant differences were observed between the CP patients with and without
      CSS. The median PSQ-minor for patients with CSS was 33.0 and without CSS was 25.0
      (P<0.05); the median PSQ-total for patients with CSS was 82.0 and without CSS was
      65 (P<0.05). The CP patients without CSS did not show any significant difference
      compared with the AP and HS groups, except for catastrophising. CONCLUSIONS: This
      study highlights the influence of CSS in the results of PSQ and catastrophising
      by chronic pain patients in comparison with healthy controls and acute pain
      patients. CLINICAL TRIAL REGISTRATION: P2014/134.

PMID- 30115263
TI  - Liberal fluid fasting: impact on gastric pH and residual volume in healthy
      children undergoing general anaesthesia for elective surgery.
AB  - BACKGROUND: The paediatric preoperative fasting time of 2 h for clear fluids, as
      suggested by guidelines, is often exceeded. Shorter preoperative fasting has been
      proposed to avoid potential outcomes such as dehydration, ketoacidosis, reduced
      arterial blood pressure, and patient discomfort. The aim of this study was to
      investigate whether liberal clear fluid intake until premedication significantly
      reduces actual fasting time and impacts gastric pH and residual volume. METHODS:
      Children (1-16 yr old, ASA I or II) undergoing elective procedures with general
      anaesthesia requiring tracheal intubation were randomised for clear fluid intake
      until premedication with midazolam (liberal) or 2 h fluid fasting (standard).
      Actual fasting times were recorded. Gastric content was sampled after tracheal
      intubation with an orogastric tube to determine gastric pH and residual volume.
      Data are presented as median [interquartile range]. RESULTS: We included 162
      children aged 1.1-16 yr; gastric pH was determined in 138 patients. Patients'
      characteristics were similar in the two groups. The liberal fasting group had
      significantly shorter fasting times (48 [18.5-77.5] vs 234 [223.5-458.5] min;
      P<0.001). No significant difference was observed regarding gastric pH (1.6 [1.5
      1.8] vs 1.6 [1.4-1.7]; P=0.237) or residual volume (0.38 [0.1-1.1] vs 0.43 [0.13
      0.73] ml kg-1; P=0.535). Twelve patients (15%) in the liberal group (median fluid
      fasting 32 min) vs one patient (1%) had gastric residual volumes >2 ml kg-1
      (P=0.001). CONCLUSION: Fluid intake until premedication allows for significantly
      shorter fasting times. Elevated gastric residual volumes may occur more often in
      patients with fasting times of 30 min or shorter. CLINICAL TRIAL REGISTRATION:
      NCT02603094.

PMID- 30115261
TI  - Somatosensory function and pain in extremely preterm young adults from the UK
      EPICure cohort: sex-dependent differences and impact of neonatal surgery.
AB  - BACKGROUND: Surgery or multiple procedural interventions in extremely preterm
      neonates influence neurodevelopmental outcome and may be associated with long
      term changes in somatosensory function or pain response. METHODS: This
      observational study recruited extremely preterm (EP, <26 weeks' gestation; n=102,
      60% female) and term-born controls (TC; n=48) aged 18-20 yr from the UK EPICure
      cohort. Thirty EP but no TC participants had neonatal surgery. Evaluation
      included: quantitative sensory testing (thenar eminence, chest wall); clinical
      pain history; questionnaires (intelligence quotient; pain catastrophising;
      anxiety); and structural brain imaging. RESULTS: Reduced thermal threshold
      sensitivity in EP vs TC participants persisted at age 18-20 yr. Sex-dependent
      effects varied with stimulus intensity and were enhanced by neonatal surgery,
      with reduced threshold sensitivity in EP surgery males but increased sensitivity
      to prolonged noxious cold in EP surgery females (P<0.01). Sex-dependent
      differences in thermal sensitivity correlated with smaller amygdala volume
      (P<0.05) but not current intelligence quotient. While generalised decreased
      sensitivity encompassed mechanical and thermal modalities in EP surgery males, a
      mixed pattern of sensory loss and sensory gain persisted adjacent to neonatal
      scars in males and females. More EP participants reported moderate-severe
      recurrent pain (22/101 vs 4/48; chi2=0.04) and increased pain intensity
      correlated with higher anxiety and pain catastrophising. CONCLUSIONS: After
      preterm birth and neonatal surgery, different patterns of generalised and local
      scar-related alterations in somatosensory function persist into early adulthood.
      Sex-dependent changes in generalised sensitivity may reflect central modulation
      by affective circuits. Early life experience and sex/gender should be considered
      when evaluating somatosensory function, pain experience, or future chronic pain
      risk.

PMID- 30115264
TI  - Randomised controlled trial comparing preoperative carbohydrate loading with
      standard fasting in paediatric anaesthesia.
AB  - BACKGROUND: Preoperative fasting is a major cause of perioperative discomfort in
      paediatric anaesthesia and leads to postoperative insulin resistance, thus
      potentially enhancing the inflammatory response to surgery. Addressing these
      problems by preoperative carbohydrate intake has not been a well-defined approach
      in children. METHODS: We randomised 120 children scheduled for gastroscopy under
      general anaesthesia to either a control group of standard preoperative fasting or
      a study group receiving a carbohydrate beverage (PreOpTM; Nutricia, Erlangen,
      Germany). Their stomach contents were aspirated endoscopically, and the volume
      and pH measured. Perioperative discomfort was evaluated using, among other
      parameters, an observational pain scale in <=4-yr-olds and a VAS in >4-yr-olds.
      The investigators doing the endoscopies and outcome evaluations were blinded to
      the study group allocation. RESULTS: Compared with fasting, carbohydrate loading
      was associated with significantly less gastric content (P=0.01), fewer patients
      experiencing postoperative nausea (P=0.028), with no significant difference in
      postoperative vomiting. High preoperative VAS scores (>5) were recorded for only
      one child in the carbohydrate group vs five children in the fasting group. Bowel
      cleansing for simultaneous colonoscopies (n=61) made no difference to any of the
      intergroup findings. CONCLUSIONS: Preoperative carbohydrates can reduce nausea
      and gastric content, the latter being a surrogate parameter for the risk and
      severity of gastric aspiration into the lungs during anaesthesia. Our study adds
      knowledge for preoperative fasting guidelines in paediatric anaesthesia. CLINICAL
      TRIAL REGISTRATION: DRKS00005020.

PMID- 30115262
TI  - Conditioned pain modulation identifies altered sensitivity in extremely preterm
      young adult males and females.
AB  - BACKGROUND: Conditioned pain modulation is a potential biomarker for risk of
      persistent pain. As early-life experience can alter subsequent somatosensory
      processing and pain response, we evaluated conditioned pain modulation after
      extremely preterm birth. METHODS: This observational study recruited extremely
      preterm (<26 weeks gestation; n=98) and term-born control (n=48) young adults (19
      20 yr) from the longitudinal EPICure cohort. Pressure pain threshold (PPT;
      variable test stimulus lower leg) was measured before, during, and after a
      conditioning stimulus (contralateral hand immersion; 5 degrees C water; 30 s).
      Questionnaires assessed current pain, medication use, anxiety, and pain
      catastrophising. RESULTS: For participants tolerating conditioning, there were
      significant main effects of extremely preterm status, sex, and time on PPT during
      and after hand immersion. Inhibitory modulation was evoked in 64/98 extremely
      preterm (3, no change) and 38/48 term-born control (3, facilitation) subjects.
      The conditioned pain modulation effect (percentage change in PPT) did not differ
      between the extremely preterm and term-born control groups {53% [95% confidence
      interval (CI): 41-65] vs 57% [95% CI: 42-71]}. Reduced cold tolerance (<20 s)
      hampered conditioned pain modulation quantification in a higher proportion of
      extremely preterm participants [extremely preterm vs term-born control: 31/98
      (32%) vs 7/48 (15%); P=0.03]. One-third of extremely preterm females withdrew the
      hand before parallel PPT (<15 s), and had lower baseline PPT than term-born
      control females [4.9 (95% CI: 4.8-5.1) vs 5.3 (95% CI: 5.1-5.5) ln kPa; P=0.02].
      Higher anxiety, pain catastrophising, and medication use correlated with pain
      intensity, but not conditioned pain modulation effect. CONCLUSIONS: Cold
      conditioning evoked inhibitory modulation in the majority of young adults and
      identified a subgroup of extremely preterm females with increased baseline
      sensitivity. Early-life experience and sex/gender should be considered when
      evaluating persistent pain risk with conditioned pain modulation.

PMID- 30115266
TI  - Dynamic arterial elastance might not be an indicator of ventriculo-arterial
      coupling. Comment on Br J Anaesth 2017; 118: 938-46.

PMID- 30115265
TI  - Using an animated patient avatar to improve perception of vital sign information
      by anaesthesia professionals.
AB  - BACKGROUND: Maintaining situation awareness of monitored patients can be
      challenging because care providers must continually read and integrate multiple
      waveforms and numerical vital sign values into a mental model of the patient's
      situation. We developed and evaluated a technology designed to improve perception
      of vital sign information by presenting patient status as an animated patient
      avatar. METHODS: After step-wise improvement of the avatar, anaesthesia
      professionals from two hospitals participated in a comparative study of
      conventional monitoring. Participants observed identical monitoring scenarios via
      the two technologies for brief time intervals and afterwards recalled patient
      status. RESULTS: Overall, 150 anaesthesia professionals participated in the
      validation process and 32 participated in the comparative study, completing 128
      scenarios, which allowed for 64 direct comparisons. The avatar's inter-rater
      reliability was high, with Fleiss' kappa of 0.98 (95% confidence interval 0.96
      0.99, P<0.001). With the avatar, participants recalled almost twice as many vital
      signs correctly as with conventional monitoring (9 vs 5, P<0.001). Perceived
      confidence was improved (2=certain vs 1=uncertain, P<0.001) and perceived
      workload lowered (task load index 60 vs 76, P<0.001). Participants obtained these
      results only after watching an educational video explaining the avatar and
      suggesting quick learnability and potential for real-life usability. CONCLUSIONS:
      This study provides empirical evidence that an animated avatar offers the
      opportunity to transmit vital sign information significantly more quickly than
      conventional monitoring and with improved confidence and reduced cognitive
      effort. This could help care providers gain situation awareness more efficiently.

PMID- 30115267
TI  - Goal-directed fluid therapy in the era of enhanced recovery after surgery: the
      jury is still out. Comment on Br J Anaesth 2018; 120: 734-44.

PMID- 30115268
TI  - Use of inferior vena cava ultrasonography to guide fluid therapy. Comment on Br J
      Anaesth 2018; 120: 101-8.

PMID- 30115270
TI  - Fibreoptic tracheal intubation: blind or direct vision. Comment on Br J Anaesth
      2018; 120:1139-40.

PMID- 30115269
TI  - Personalised anaesthesia: three-dimensional printing of facial prosthetic for
      facial deformity with difficult airway.

PMID- 30115271
TI  - Tracheal tube impingement during oral fibreoptic intubation. Comment on Br J
      Anaesth 2018; 120: 1139-40.

PMID- 30115272
TI  - Use of OptiflowTM nasal high-flow oxygen in a patient with malignant
      hyperthermia.

PMID- 30115273
TI  - A genetic mystery in malignant hyperthermia 'solved'?

PMID- 30115275
TI  - Comment on 'Cutaneous innervation of the hand: clinical testing in volunteers
      shows high intra- and inter-individual variability' (Br J Anaesth 2018; 120: 836
      45).

PMID- 30115274
TI  - Enhanced recovery protocol in total hip replacement does not increase general
      practitioner visits.

PMID- 30115276
TI  - Authors' response to a comment on 'Cutaneous innervation of the hand: clinical
      testing in volunteers shows high intra- and inter-individual variability' (Br J
      Anaesth 2018; 120:836-45).

PMID- 30115277
TI  - Corrigendum to 'Local anaesthetic dosage of peripheral nerve blocks in children:
      analysis of 40 121 blocks from the pediatric regional anesthesia network
      database' (Br J Anaesth 2018;120: 317-322).

PMID- 30115278
TI  - Corrigendum to "Pharmacokinetic and pharmacodynamic study of intranasal and
      intravenous dexmedetomidine" (Br J Anaesth 2018; 120: 960-968).

PMID- 30115279
TI  - Optimization of femtosecond lasers using porcine and human donor corneas before
      in vivo use.
AB  - PURPOSE: To demonstrate a safe and effective method of optimizing a femtosecond
      laser upon installation or for a new procedure before use on patients. In this
      case, specifically for optimizing settings for intrastromal corneal pocket
      creation for the presbyopic small-aperture corneal inlay (Kamra) and deep laser
      in situ keratomileusis (LASIK) flaps for the presbyopic hydrogel corneal inlay
      (Raindrop). SETTING: Keil LASIK Vision Center, Grand Rapids, Michigan, USA.
      DESIGN: Experimental study. METHODS: Human donor corneas were used to optimize
      femtosecond laser settings after initial optimization with porcine corneas. The
      laser used was the Femto LDV Z4. RESULTS: Pocket settings optimized for porcine
      corneas were 12.0 mm/s pocket and tunnel at 105% energy; whereas, settings
      optimized with human donor corneas were 13.0 mm/s pocket and tunnel at 110%
      energy. Settings optimized with human donor corneas were subsequently applied in
      vivo to create pockets for the small-aperture corneal inlay. Further adjustment
      of settings to 14.0 mm/s pocket at 110% energy was still necessary to optimize
      pockets. No change in settings was necessary when creating deeper corneal LASIK
      flaps (ie, the same settings could be used for flaps of 110 MUm or 180 MUm).
      CONCLUSIONS: After settings were optimized for porcine corneas, further
      optimization was necessary before successful corneal incisions could be created
      in vivo for corneal pockets. No further optimization was required when creating
      deeper corneal flaps for the hydrogel inlay. It is important to emphasize that
      settings obtained and reported here are not applicable to other femtosecond
      lasers.

PMID- 30115281
TI  - August consultation #3.

PMID- 30115280
TI  - Small-aperture intraocular lens combined with secondary piggyback intraocular
      lens during cataract surgery after previous radial keratotomy.
AB  - A 73-year-old woman with bilateral previous radial keratotomies (RK) and
      symptomatic cataracts was referred. The uncorrected distance visual acuity (UDVA)
      was 0.24 logarithm of the minimum angle of resolution (logMAR) in the left eye
      and 0.32 logMAR in the left eye. The American Society of Cataract and Refractive
      Surgery calculator for eyes with previous RK was used for intraocular lens (IOL)
      power calculation. The dominant left eye had uneventful cataract extraction with
      monofocal IOL implantation. For the nondominant right eye, a small-aperture
      posterior chamber IOL with the highest available power was used; this was
      followed by planned secondary piggyback sulcus IOL implantation for the expected
      residual refractive error. The UDVA after the primary procedure was 0.50 logMAR
      in the right eye and 0.10 logMAR in the left eye. After the planned secondary
      procedure, the UDVA was -0.10 logMAR in both eyes with a -0.50 diopter spherical
      equivalent and the patient did not require spectacles for near, intermediate, or
      distance vision.

PMID- 30115282
TI  - August consultation #2.

PMID- 30115283
TI  - Extreme intraocular pressure, mild glaucoma, and previous canaloplasty with
      indwelling suture: August consultation #1.

PMID- 30115285
TI  - August consultation #5.

PMID- 30115284
TI  - August consultation #4.

PMID- 30115286
TI  - August consultation #7.

PMID- 30115287
TI  - August consultation #6.

PMID- 30115288
TI  - Editor's Comment.

PMID- 30115289
TI  - Reply.

PMID- 30115290
TI  - Rate of complete capsulotomies from precision pulse technology.

PMID- 30115291
TI  - Comment on the ESCRS PREMED study.

PMID- 30115292
TI  - Reply.

PMID- 30115293
TI  - Small aperture intraocular lenses: The new kids on the block.

PMID- 30115294
TI  - Flapless and sutureless intrascleral fixation of posterior chamber intraocular
      lens for correction of aphakia.
AB  - A new intrascleral fixation technique for a standard 3-piece posterior chamber
      intraocular lens (PC IOL) using a simple guide is described. To secure the
      haptics, 27-gauge scleral tunnels are created. Both haptics are secured
      extraocularly. The leading haptic of the PC IOL placed in the cartridge is
      released partly and introduced into the lumen of the guide. The PC IOL is
      inserted into the eye, and the leading haptic is externalized by pulling the
      guide gently through the 27-gauge sclerotomy site. The trailing haptic is
      externalized using the same procedure. This technique facilitates achieving
      minimally invasive sutureless intrascleral PC IOL fixation.

PMID- 30115295
TI  - Microinterventional endocapsular nucleus disassembly for phacoemulsification-free
      full-thickness fragmentation.
AB  - We describe a new technique for nucleus disassembly using a microinterventional
      approach. This is the first report of a microinterventional phacoemulsification
      free endocapsular lens fragmentation using a superelastic memory-shaped nickel
      and titanium (nitinol) microfilament (miLOOP). After standard capsulorhexis and
      hydrodissection, the microinterventional loop is inserted through the 2.3 mm
      clear corneal incision. An actuation mechanism is used to unfold the microloop,
      which glides horizontally on the anterior surface of the lens, expands below the
      anterior capsule, and then rotates vertically while traveling in the
      hydrodissection plane to encircle the entire nucleus. Then, the loop is
      mechanically retracted within the sleeve, achieving full-thickness centripetal
      segmentation of the nucleus. After rotation of the lens, the loop cuts can be
      repeated to create 4 or more segments without using phaco energy. The technique
      is independent of cataract grade and eliminates the need for phacoemulsification
      or femtosecond energy during the nucleus disassembly step of cataract surgery.

PMID- 30115296
TI  - Comparison of 9 modern intraocular lens power calculation formulas for a
      quadrifocal intraocular lens.
AB  - PURPOSE: To evaluate the accuracy of 9 formulas (Barrett Universal II, Haigis,
      Hill-Radial Basis Function [RBF], Hoffer Q, Holladay 1, Holladay 2, Olsen,
      Sanders-Retzlaff-Kraff/theoretical [SRK/T], and T2) calculating the power of the
      quadrifocal Acrysof IQ Panoptix TFNT00 intraocular lens (IOL). SETTING:
      Department of Ophthalmology, Goethe University, Frankfurt, Germany. DESIGN:
      Retrospective case series. METHODS: The study included patients having cataract
      surgery with insertion of a quadrifocal IOL over 15 months. Preoperative biometry
      measurements were obtained from an IOLMaster 500. Optimized IOL constants were
      calculated to reduce the mean refractive prediction error. The primary outcomes
      were differences in mean absolute prediction error between the formulas. Median
      and maximum absolute prediction errors were evaluated as well as percentages of
      eyes within prediction errors of +/-0.25 diopters (D), +/-0.50 D, +/-1.00 D, and
      +/-2.00 D. RESULTS: The study comprised 75 eyes of 38 patients. The formulas were
      ranked by the mean absolute refractive prediction error as follows: Barrett
      Universal II (0.294 D), Hill-RBF (0.332 D), Olsen (0.339 D), T2 (0.351 D),
      Holladay 1 (0.381 D), Haigis (0.382 D), SRK/T (0.393 D), Holladay 2 (0.399 D),
      and Hoffer Q (0.410 D). The differences in absolute errors between the formulas
      were significant (P < .001). The lowest maximum absolute prediction error was
      obtained with the Barrett Universal II. CONCLUSION: The most accurate predictions
      of actual postoperative refraction were achieved using the Barrett Universal II,
      Hill-RBF, Olsen, or T2 formula. Thus, one of these formulas should be used for
      IOL power calculation of the quadrifocal IOL.

PMID- 30115297
TI  - Long-term comparison of postoperative refractive outcomes between
      phacotrabeculectomy and phacoemulsification.
AB  - PURPOSE: To compare long-term postoperative refractive outcomes between
      phacotrabeculectomy and phacoemulsification, both with posterior chamber
      intraocular lens implantation. SETTING: Department of Ophthalmology, Konyang
      University, Kim's Eye Hospital, Myung-Gok Eye Research Institute, Seoul, South
      Korea. DESIGN: Retrospective comparative study. METHODS: Postoperative refractive
      outcomes were compared between patients with cataract and coexisting primary or
      secondary open-angle glaucoma (OAG) who had phacotrabeculectomy (combined group)
      and patients with cataract with or without coexisting OAG who had
      phacoemulsification alone (phaco-only group). The refractive prediction error,
      mean absolute error, and median absolute error were compared between groups.
      Subgroup analysis based on preoperative axial length (AL) was performed (medium
      >22.0 to <24.5 mm; medium-long >=24.5 to <26.0 mm; long >=26.0 mm). RESULTS: The
      combined group comprised 51 eyes and the phaco-only group, 74 eyes. The mean
      interval between surgery and refraction measurement was 14.70 months +/- 10.80
      (SD) (median 13.0 months) and 4.81 +/- 4.97 months (median 2.0 months),
      respectively. Postoperatively, there was no statistically significant between
      group difference in the following mean values: refractive prediction error, -0.05
      +/- 0.64 versus -0.04 +/- 0.52 (P = .905); mean absolute error, 0.46 +/- 0.44
      versus 0.38 +/- 0.36 (P = .258); median absolute error, 0.32 (interquartile range
      [IQR], 0.17, 0.67) versus 0.28 (IQR, 0.13, 0.54) (P = .297). Subgroup analysis
      also did not show significant differences between the 2 groups (all P > .05).
      CONCLUSION: The long-term postoperative refractive outcomes of
      phacotrabeculectomy and phacoemulsification alone were not significantly
      different in eyes with OAG, regardless of preoperative AL.

PMID- 30115299
TI  - Correlation of Scheimpflug densitometry changes with clinical outcomes after
      corneal crosslinking.
AB  - PURPOSE: To characterize changes in densitometry after corneal crosslinking (CXL)
      and correlate it with visual outcomes. SETTING: Tertiary referral academic
      medical center, New York, New York, USA. DESIGN: Retrospective case series.
      METHODS: Patients with progressive keratoconus or post-laser in situ
      keratomileusis ectasia had CXL following the Dresden protocol. The corrected
      distance visual acuity (CDVA) and Pentacam imaging were obtained at baseline and
      follow-up visits. RESULTS: Fifty-seven patients were followed for a mean of 15
      months (range 1 to 24 months) after CXL. The CDVA improved significantly from
      baseline to 6, 12, 18, and 24 months postoperatively. The change in densitometry
      of the mid-stromal layer, 2.0 to 6.0 mm annulus, at 6 months was correlated with
      the improvement in CDVA at 6, 12, and 24 months (all P < .10). The increase in
      densitometry of the mid-stromal layer, centermost 0.0 to 2.0 mm annulus, at 6
      months was significantly associated with the decrease in maximum keratometry (K)
      at 6 and 12 months (both P < .05). Last, the change in densitometry at 6 months
      was significantly correlated with the decrease in specific higher-order
      aberrations (HOAs) (P < .05). CONCLUSIONS: Although the greatest and most durable
      post-CXL densitometry change was in the anterior layer, the degree of increased
      densitometry haze in the mid-stromal layer was most associated with and possibly
      predictive of improvement in CDVA, maximum K, and HOAs. The persistence of
      corneal haze at 6 months, measured by increased densitometry, might be a
      prognostic marker for CXL effectiveness.

PMID- 30115298
TI  - Analysis of cases and accuracy of 3 risk scoring systems in predicting ectasia
      after laser in situ keratomileusis.
AB  - PURPOSE: To identify risk factors for ectasia after laser in situ keratomileusis
      (LASIK) by comparing the accuracy of the Ectasia Risk Score System (ERSS),
      Screening Corneal Objective Risk of Ectasia (SCORE) Analyzer, and percentage of
      tissue altered (PTA) in predicting the occurrence of ectasia. SETTING: Multiple
      centers in 8 countries. DESIGN: Retrospective case series. METHODS: Previously
      unpublished post-LASIK ectasia cases were analyzed. Consecutive patients who had
      LASIK performed at least 5 years previously with no resultant ectasia were used
      as controls. Axial maps from preoperative Orbscan IIz topographies were analyzed
      in a masked fashion, and examination files tested with the SCORE Analyzer. The
      PTA values and ERSS scores were generated using available preoperative and
      perioperative data. Only eyes with subjectively identified normal preoperative
      topography were tested with the PTA. Threshold values for the SCORE, ERSS, and
      PTA were more than or equal to 0, 4, and 40, respectively. RESULTS: Ectasia
      occurred in 31 eyes (22 patients); 79 eyes (44 patients) were used as controls.
      In all eyes, the sensitivity and specificity for predicting ectasia,
      respectively, were 67.7% and 79.7% for the ERSS and 64.5% and 100% for the SCORE.
      In eyes with normal topography (ectasia group, 12 eyes; controls, 64 eyes), the
      PTA yielded sensitivity of 33.3% and specificity of 85.9%. The area under the
      receiver operating characteristic curve was highest for SCORE (0.911) followed by
      the ERSS (0.844) and PTA (0.557). CONCLUSIONS: The SCORE was most predictive of
      ectasia, achieving the best specificity; the ERSS had the best sensitivity.
      Further studies are required to validate the PTA as a screening metric for
      ectasia.

PMID- 30115300
TI  - Editorial to the Special Issue: Animal Model of the Year 2036: Novel Perspectives
      in Behavioral Neuroscience.

PMID- 30115301
TI  - Editorial overview: Nothing in plant-biotic interactions makes sense....

PMID- 30115302
TI  - Biliary radiofrequency ablation: burning issues.

PMID- 30115303
TI  - Per-oral endoscopic myotomy in achalasia: Which way to go-anterior or posterior?

PMID- 30115304
TI  - Response.

PMID- 30115305
TI  - Bougie cap esophageal passage: A novel potential tool for calibration of lumen
      diameter in eosinophilic esophagitis?

PMID- 30115306
TI  - Worrisome endoscopic feature in the stomach of patients with familial adenomatous
      polyposis: the proximal white mucosal patch.

PMID- 30115307
TI  - Response.

PMID- 30115308
TI  - EUS-guided biliary drainage versus ERCP for the primary treatment of malignant
      distal biliary obstruction: time for a large randomized study.

PMID- 30115309
TI  - Response.

PMID- 30115310
TI  - No difference does not always mean equivalent.

PMID- 30115311
TI  - Response.

PMID- 30115312
TI  - Role of warfarin as a predictor of recurrent bleeding after negative small-bowel
      capsule endoscopy.

PMID- 30115313
TI  - Use of N-acetylcysteine plus simethicone to improve mucosal visibility during
      upper GI endoscopy.

PMID- 30115314
TI  - Response.

PMID- 30115315
TI  - Meta-analysis evaluating colonoscopy novelties: mind the methodology!

PMID- 30115316
TI  - Response.

PMID- 30115317
TI  - Taxonomy and pathogenicity of Olpidium brassicae and its allied species.
AB  - The classification and physiology of the zoosporic plant-pathogen Olpidium
      brassicae and its relationships with the closely-related species are often
      confusing. This review focuses on these species and intends to differentiate them
      based on the literatures published since the discovery and establishment of the
      species by Woronin in 1878 under the name of Chytridium brassicae to current
      molecular era. The goal of this review is to help researchers better understand
      the taxonomy, the host range, and the potential role in plant health of O.
      brassicae-related species. To reach the goal, we reviewed the rationales behind
      the creation or reduction in synonymy of the different names for O. brassicae and
      its allied species in order to elucidate the evolution of the species concept on
      them based on the traditional morphological studies. Furthermore, the studies by
      molecular biology methods improve our knowledge and perspectives on O. brassicae
      and its host specificity. In particular, we clarify the differences between O.
      brassicae and Olpidium virulentus, and propose potential new research avenues. We
      therefore hope that this review will give a better perspective on Olpidium spp.
      and their potential role in the root microbiome of plants in natural environments
      and in agricultural settings.

PMID- 30115318
TI  - Taxonomic and phylogenetic analysis of the Oomycota mosquito larvae pathogen
      Crypticola clavulifera.
AB  - Beside the taxonomic features displayed by Crypticola clavulifera in culture and
      unpublished data on its phylogeny, little is known about the main phylogenetic
      features of this unusual mosquito pathogen. We have PCR amplified the 18S SSU
      rDNA, ITS, and the partial coding regions of COXII and COXI to study the
      phylogenetic features of this pathogen within the tree of life. Our phylogenetic
      data showed C. clavulifera clustered among homologous DNA sequences of the
      Oomycota class Saprolegniomycetes. Our study support previous taxonomic and
      unpublished molecular analysis, placing this unusual mosquito larvae pathogen as
      part of the earliest diverging cluster within the Saprolegniomycetes.

PMID- 30115319
TI  - Diversity and evolution of polyketide biosynthesis gene clusters in the
      Ceratocystidaceae.
AB  - Polyketides are secondary metabolites with diverse biological activities.
      Polyketide synthases (PKS) are often encoded from genes clustered in the same
      genomic region. Functional analyses and genomic studies show that most fungi are
      capable of producing a repertoire of polyketides. We considered the potential of
      Ceratocystidaceae for producing polyketides using a comparative genomics
      approach. Our aims were to identify the putative polyketide biosynthesis gene
      clusters, to characterize them and predict the types of polyketide compounds they
      might produce. We used sequences from nineteen species in the genera,
      Ceratocystis, Endoconidiophora, Davidsoniella, Huntiella, Thielaviopsis and
      Bretziella, to identify and characterize PKS gene clusters, by employing a range
      of bioinformatics and phylogenetic tools. We showed that the genomes contained
      putative clusters containing a non-reducing type I PKS and a type III PKS.
      Phylogenetic analyses suggested that these genes were already present in the
      ancestor of the Ceratocystidaceae. By contrast, the various reducing type I PKS
      containing clusters identified in these genomes appeared to have distinct
      evolutionary origins. Although one of the identified clusters potentially allows
      for the production of melanin, their functional characterization will undoubtedly
      reveal many novel and important compounds implicated in the biology of the
      Ceratocystidaceae.

PMID- 30115320
TI  - Comparison of fungal communities among ten macrophyte rhizospheres.
AB  - The fungal community composition, size and several physico-chemical properties
      were individually investigated in ten macrophyte rhizospheric substrates using
      nested PCR-denaturing gradient gel electrophoresis and soil chemical methods.
      Results indicated that both Dothideomycetes and Sordariomycetes were dominant
      fungi in macrophyte rhizospheric substrates, and denitrifying fungi (Fusarium
      graminearum) was found in nine of ten macrophyte rhizospheres. Fungal Shannon
      Wiener diversity index (H) and richness (S) in Thalia dealbata, Typha latifolia,
      Iris hexagona and Hemerocallis aurantiaca rhizospheres were higher than those in
      other six rhizospheres. Fungal number and biomass were 1.91 * 103 CFUs g-1 dw and
      1.53 MUg ergosterol g-1 dw in Iris pseudacor rhizosphere, and were greater than
      in other nine rhizospheres. The correlation analysis showed that fungal number
      and biomass significantly and positively correlated to total soil phosphorus,
      while fungal H and S were significantly and negatively correlated to total
      organic carbon. The principal components analysis (PCA) showed that the fungal
      community significantly divided ten macrophyte rhizospheres into four groups,
      showing the significant difference of fungal communities among ten rhizospheric
      substrates. The current study revealed for the first time the importance of
      rhizospheric fungal community in distinguishing macrophyte rhizospheres, thus
      will undoubtedly widen our insight into fungal communities in aquatic
      rhizospheres.

PMID- 30115321
TI  - Heterologous expression, purification and characterization of a highly
      thermolabile endoxylanase from the Antarctic fungus Cladosporium sp.
AB  - Numerous endoxylanases from mesophilic fungi have been purified and
      characterized. However, endoxylanases from cold-adapted fungi, especially those
      from Antarctica, have been less studied. In this work, a cDNA from the Antarctic
      fungus Cladosporium sp. with similarity to endoxylanases from glycosyl hydrolase
      family 10, was cloned and expressed in Pichia pastoris. The pure recombinant
      enzyme (named XynA) showed optimal activity on xylan at 50  degrees C and pH 6-7.
      The enzyme releases xylooligosaccharides but not xylose, indicating that XynA is
      a classical endoxylanase. The enzyme was most active on xylans with high content
      of arabinose (rye arabinoylan and wheat arabinoxylan) than on xylans with low
      content of arabinose (oat spelts xylan, birchwood xylan and beechwood xylan).
      Finally, XynA showed a very low thermostability. After 20-30 min of incubation at
      40  degrees C, the enzyme was completely inactivated, suggesting that XynA would
      be the most thermolabile endoxylanase described so far in filamentous fungi. This
      is one of the few reports describing the heterologous expression and
      characterization of a xylanase from a fungus isolated from Antarctica.

PMID- 30115322
TI  - Modified Adamek's medium renders high yields of Metarhizium robertsii
      blastospores that are desiccation tolerant and infective to cattle-tick larvae.
AB  - Blastospores are yeast-like cells produced by entomopathogenic fungi that are
      infective to arthropods. The economical feasible production of blastospores of
      the insect killing fungus Metarhizium spp. must be optimized to increase yields.
      Moreover, stabilization process is imperative for blastospore formulation as a
      final product. In this sense, our goal was to increase blastospore production of
      two Metarhizium isolates (ESALQ1426 and ESALQ4676) in submerged liquid cultures.
      A modified Adamek's medium was supplemented with increased glucose concentrations
      and the fermentation time was accelerated by using a blastospore pre-culture as
      inoculum. Virulence of air-dried stable blastospores was compared with conidia
      toward larvae of the cattle tick, Rhipicephalus microplus. Our results revealed
      that blastospore production of Metarhizium is isolate- and species-dependent.
      Glucose-enriched cultures (140 g glucose/L) inoculated with pre-cultures improved
      yields with optimal growth conditions attained for Metarhizium robertsii
      ESALQ1426 that rendered as high as 5.9 * 108 blastospores/mL within 2 d.
      Resultant air-dried blastospores of ESALQ1426 were firstly proved to infect and
      quickly kill cattle tick larvae with comparable efficiency to conidia.
      Altogether, we argue that both osmotic pressure, induced by high glucose titers,
      and isolate selection are critical to produce high yields of blastospores that
      hold promise to control cattle-tick larvae.

PMID- 30115323
TI  - Genetic diversity of the entomopathogenic fungus Cordyceps tenuipes in forests
      and butterfly gardens in Quindio, Colombia.
AB  - Cordyceps tenuipes is an entomopathogenic fungus that infects mostly pupae of
      several lepidopteran families. In Colombia the species has been reported in non
      disturbed tropical rain forests and more recently in butterfly gardens. The aim
      of this study was to assess the genetic diversity in populations of C. tenuipes
      present in natural (forests) and artificial (e.g. butterfly gardens) environments
      in the department of Quindio, Colombia, using three molecular nuclear markers
      ITS, TEF-1alpha and RPB1. All the samples evaluated corresponded morphologically
      and phylogenetically to C. tenuipes. The butterfly garden of Quindio Botanical
      Garden (QBG) showed the highest genetic diversity among all sampling localities
      and was very similar to that of its adjacent forest. The Amaranta Butterfly
      Garden (ABG), located north of QBG, showed lower genetic diversity as well as
      little genetic differentiation with QBG, consistent with the hypothesis of a
      pathogen transfer from QBG to ABG. Higher FST values were observed for TEF-1alpha
      and ITS, revealing genetic differentiation between all demes and the southern
      forest population. Our research constitutes the first study of the intraspecific
      diversity of C. tenuipes in Colombia and can serve as the first step in
      identifying diversity reservoirs and management of epizootic episodes caused by
      this fungal species.

PMID- 30115324
TI  - Ophiostoma quercus: An unusually diverse and globally widespread tree-infecting
      fungus.
AB  - Ophiostoma quercus (Ascomycota, Ophiostomatales) is a globally widespread, insect
      vectored fungus that colonizes a wide diversity of hardwood and conifer hosts.
      Although the fungus is considered to be non-pathogenic, it is closely related to
      the fungi that cause Dutch elm disease. We examined the global diversity of O.
      quercus based on a ribosomal RNA marker and three unlinked gene regions. The
      fungus exhibited substantial morphological diversity. In addition, O. quercus had
      high genetic diversity in every continent from which it was collected, although
      the fungus was most diverse in Eurasia. There was no evidence of geographical
      clustering of haplotypes based on phylogenetic and network analyses. In addition,
      the phylogenetic trees generated based on the different markers were non
      congruent. These results suggest that O. quercus has been repeatedly moved around
      the globe, because of trade in wood products, and that the fungal species most
      likely outcrosses regularly. The high genetic diversity of the fungus, as well as
      its ability to utilize a wide variety of arthropod vectors and colonize a
      tremendous diversity of tree host species makes O. quercus truly unique among
      ophiostomatoid fungi.

PMID- 30115326
TI  - Mycorrhizal inoculation as an alternative for the sustainable production of
      Mimosa tenuiflora seedlings with improved growth and secondary compounds content.
AB  - In this study, we report the effects of arbuscular mycorrhizal fungi (AMF) and
      increasing doses of phosphorus (P) on the growth and production of secondary
      metabolites in Mimosa tenuiflora, a medicinal species native to Brazil. We used a
      completely randomized design with four inoculation treatments: Control not
      inoculated (1); Claroideoglomus etunicatum (2); Gigaspora albida (3); and C.
      etunicatum + G. albida (4) and four doses of P; P0 - baseline dose, P8, P16 and
      P32. After 70 d in a greenhouse, growth, mycorrhizal variables, biochemical and
      phytochemical parameters were evaluated. Compared to non-mycorrhizal plants,
      mycorrhized M. tenuiflora seedlings showed greater: growth, greater
      photosynthetic performance and content of soluble carbohydrates and secondary
      metabolites, with the most significant benefits occurring in soil with low to
      moderate P content (up to 16 mg kg-1). The plant growth is severely restricted at
      low P levels, but the addition of AMF appears to remove this limiting factor.
      Although M. tenuiflora responds to levels of phosphate fertilization, it responds
      well to mycorrhizal inoculation, especially with G. albida, which promotes
      benefits for the initial growth and secondary metabolite content in this plant
      species of medical and potential commercial interest and may be used instead of
      phosphate fertilizer.

PMID- 30115325
TI  - Emerging new crown symptoms on Castanea sativa (Mill.): Attempting to model
      interactions among pests and fungal pathogens.
AB  - In the 2015-2016 growing seasons, two novel symptoms were assessed on the crown
      of trees in orchards and coppices of chestnut groves in Central Italy. The first
      symptom was flagging of annual shoots with green leaves undergoing sudden wilt
      and turning brown later in the season. The second symptom consisted of leaves on
      annual shoots turning yellow before wilting in absence of flagging represented
      the second symptom. Samples were collected along transects in early summer, late
      summer and winter, and processed in the laboratory. The flagging symptom was
      associated in early summer with the presence of C. parasitica in cryptic dried
      buds on stems from the previous year's growth. The pathogen was also found in
      dormant buds in winter, suggesting that the infection could take place in summer
      during the Chinese gall wasp oviposition period. Cryphonectria parasitica was
      also isolated from abandoned galls in winter supporting the hypothesis that galls
      are a potential source of inoculum for crown infections. Aetiology of yellowing
      was not clarified and no fungal taxa were specifically associated with this
      symptom. Gnomoniopsis castanea, C. parasitica and, in early summer,
      Colletotrichum acutatum were the most abundant fungal taxa isolated from chestnut
      shoots and buds.

PMID- 30115327
TI  - Temporal shifts of fungal communities in the rhizosphere and on tubers in potato
      fields.
AB  - Soil fungal communities perform important ecological roles determining, at least
      in part, agricultural productivity. This study aimed at examining the fungal
      community dynamics in the potato rhizosphere across different development stages
      in two consecutive growing seasons (winter and summer). Microbial fingerprinting
      of rhizosphere soil samples collected at pre-planting, tuber initiation,
      flowering and at senescence was performed using ARISA in conjunction with Next
      Generation Sequencing (Illumina MiSeq). The epiphytic fungal communities on
      tubers at harvest were also investigated. Alpha-diversity was stable over time
      within and across the two seasons. In contrast, rhizospheric fungal community
      structure and composition were different between the two seasons and in the
      different plant growth stages within a given season, indicating the significance
      of the rhizosphere in shaping microbial communities. The phylum Ascomycota was
      dominant in the potato fungal rhizosphere, with Operational Taxonomic Units
      (OTUs) belonging to the genus Peyronellaea being the most abundant in all
      samples. Important fungal pathogens of potato, together with potential biological
      control agents and saprophytic species, were identified as indicator OTUs at
      different plant growth stages. These findings indicate that potato rhizosphere
      fungal communities are functionally diverse, which may contribute to soil health.

PMID- 30115328
TI  - Omics tools for the needle out of haystack?

PMID- 30115329
TI  - Tick-Borne Illnesses in the United States.
AB  - Close interaction with nature can lead to tick-borne illnesses, which are seen
      most frequently in primary care clinics when patients present symptoms.
      Considerable morbidity can result from untreated infections. Fortunately, these
      illnesses are often easily managed when diagnosed early.

PMID- 30115330
TI  - Mosquito-Borne Diseases.
AB  - Mosquito-borne diseases have become more common as previously geographically
      isolated diseases have spread globally. Chikungunya, dengue, Japanese
      encephalitis, malaria, West Nile, yellow fever, and Zika are a few of the common
      and emerging viral diseases spread by mosquitoes. A thorough patient history,
      physical, and knowledge of diagnostic testing based on symptom duration is
      important to make a quick and accurate diagnosis. Because the treatment for many
      of these diseases is supportive, the emphasis is on reducing risk and spread of
      infection.

PMID- 30115331
TI  - Mite and Bed Bug Infections.
AB  - Patients with suspected bites or skin rashes regularly present to their primary
      care physician. Common mite infections encountered in the primary care office
      include scabies, chiggers, grain itch, and allergic responses from dust mites. In
      fact, scabies is one of the 50 most prevalent diseases worldwide. Bed bugs are
      also becoming increasingly common, living in dark crevices, such as mattresses,
      feeding at night, and causing a maculopapular immune mediated allergic skin
      response in humans. Proper identification of the mite or bed bug is essential to
      guide treatment and eradication.

PMID- 30115332
TI  - Pertussis: The Whooping Cough.
AB  - Bordetella pertussis can cause serious and potentially fatal complications,
      especially in very young infants. Early diagnosis and treatment of pertussis with
      a macrolide antibiotic, such as azithromycin, before the paroxysmal stage of
      disease can help mitigate complications and reduce the spread of this highly
      contagious disease.

PMID- 30115333
TI  - Skin Infections.
AB  - The primary care provider will commonly see skin and soft tissue infections in
      the outpatient setting. Skin and soft tissue infections range from the
      uncomplicated impetigo to the potentially lethal necrotizing fasciitis. This
      article reviews these infections based on their underlying etiology: bacterial,
      fungal, and viral causes. This article discusses the etiology, presentation,
      evaluation, and management of impetigo, bullous impetigo, erysipelas, cellulitis,
      periorbital cellulitis, orbital cellulitis, folliculitis, furuncles, carbuncles,
      abscess, necrotizing fasciitis, sporotrichosis, tinea corporis, tinea pedis,
      tinea capitis, Herpes Simplex Virus, zoster, molluscum contagiosum, and warts.

PMID- 30115334
TI  - Urinary Tract Infection Antibiotic Resistance in the United States.
AB  - Urinary tract infection (UTI) is one of the most common entities in medicine and
      affected patients present daily in a typical family medicine practice. The
      patients often present with the "classic symptoms" of dysuria and increased
      frequency, but sometimes they are asymptomatic or have a mixed picture. In most
      cases, an antibiotic is prescribed, and this practice is likely contributing to
      increasing worldwide antibiotic resistance. To help combat this problem, it is
      important that clinicians seek out their local bacterial resistance patterns and
      antibiograms, properly diagnose and treat UTI if indicated, and recognize their
      role in antibiotic stewardship.

PMID- 30115335
TI  - Emergence of Global Antibiotic Resistance.
AB  - Antibiotic resistance is a worldwide phenomenon and a global public health
      crisis. The inappropriate use of antibiotics in the human, animal, food, and
      agricultural arenas have contributed to the current dilemma. Both gram-positive
      and gram-negative resistant bacteria have been deemed serious and urgent threats
      by the Centers for Disease Control and Prevention. The World Health Organization
      has created a 5-objective global action plan to address antimicrobial resistance
      and to coordinate numerous international sectors. Antibiotic resistance affects
      both this generation and the next; thus, related ethical challenges, such as
      patient autonomy and justice have yet to be fully understood.

PMID- 30115336
TI  - Guidelines for the Evaluation and Treatment of Pneumonia.
AB  - Pneumonia is a common cause of respiratory infection, accounting for more than
      800,000 hospitalizations in the United States annually. Presenting symptoms of
      pneumonia are typically cough, pleuritic chest pain, fever, fatigue, and loss of
      appetite. Children and the elderly have different presenting features of
      pneumonia, which include headache, nausea, abdominal pain, and absence of one or
      more of the prototypical symptoms. Knowledge of local bacterial pathogens and
      their antibiotic susceptibility and resistance profiles is the key for effective
      pharmacologic selection and treatment of pneumonia.

PMID- 30115337
TI  - Central Nervous System Infections.
AB  - Infections of the nervous system are potential life-threatening and are caused by
      pathogens such as bacteria, viruses, and fungi. Prompt recognition and treatment
      of a central nervous system (CNS) infection is crucial for patient survival, as
      these infections have a high morbidity and mortality. CNS infections include
      meningitis, encephalitis, and brain abscesses. This article seeks to detail the
      etiology, clinical course, diagnostic challenges, and treatment of CNS infections
      organized by infectious agent.

PMID- 30115338
TI  - Common Gastrointestinal Infections.
AB  - Gastrointestinal infections account for a large burden of acute and chronic
      disease, with diarrhea being the most common manifestation. Most cases are due to
      viruses, with norovirus being the most common, whereas bacteria and parasites are
      also important contributors to acute and chronic gastrointestinal infections and
      their sequelae. Nontyphoidal Salmonella species cause the most hospitalizations
      and deaths in the United States. This article reviews an evidence-based approach
      to diarrhea evaluation with a focus on pathogen-specific testing and management
      for the most common viral, bacterial, and parasitic causes in the United States.

PMID- 30115339
TI  - Role of Complementary and Alternative Therapies in Infectious Disease.
AB  - Complementary and alternative medicine (CAM) is increasingly being used in
      Western countries despite the lack of conclusive research studies. Several CAM
      modalities have only shown variable therapeutic efficacy in infectious disease
      management. Clinicians should be familiar with these therapies in order to advise
      patients about alternative therapeutic options when treating infections.

PMID- 30115340
TI  - Health Guidelines for Travel Abroad.
AB  - Most travel medical care is provided by patients' primary care physicians; only
      10% of international travelers visit a travel clinic. The main purposes for
      travel include vacationing, visiting friends and family, business, and for
      educational purposes. The purposes of the pretravel consultation are to estimate
      risk and provide recommendations to mitigate risk.

PMID- 30115341
TI  - Approach to Aquatic Skin Infections.
AB  - Aquatic-based infections can present a treatment challenge for primary care
      physicians because of the likely polymicrobial nature of the infection and the
      possibility of uncommon pathogenic organisms. Although Staphylococcus and
      Streptococcus species that colonize the skin are the most common etiologic agents
      associated with saltwater and freshwater skin and soft tissue infections, other
      significant pathogens can include Vibrio, Aeromonas, Edwardsiella,
      Erysipelothrix, and Mycobacterium. Early detection and appropriate management of
      aquatic infections can significantly decrease morbidity and mortality. This
      article reviews the pathophysiology, presentation, and management for the most
      common water-borne pathogens causing skin and soft tissue infections.

PMID- 30115342
TI  - Infections During Pregnancy.
AB  - Several infections have unique consequences or considerations in pregnancy. Some
      common infections such as urinary tract infections, influenza, sexually
      transmitted diseases, and vaginitis affect pregnant women differently than the
      general population, can cause pregnancy complications, and require treatments
      that are safe in pregnancy. Infections such as hepatitis B and C and human
      immunodeficiency virus can be transmitted vertically and therefore management
      focuses on decreasing perinatal transmission. Certain infections can be
      transmitted in utero and cause congenital infections. Classically, these were
      grouped together as the TORCH infections, although now several others, including
      varicella virus, parvovirus, and Zika virus, have also been recognized.

PMID- 30115343
TI  - "Tick, Tick, Tick...".

PMID- 30115344
TI  - Infectious Disease Topics for Primary Care.

PMID- 30115345
TI  - Reliability and validity of the family satisfaction instrument in families of
      children with pneumonia.
AB  - OBJECTIVE: Family satisfaction has become an integral part of quality of care in
      hospitals. Thus, it is crucial to develop instruments that measure family
      satisfaction. The purpose of this study was to examine the validity and
      reliability of a family satisfaction questionnaire. METHOD: This study used a
      survey questionnaire consisting of 26 items that identified nurses' constructs of
      behaviors and communication. The population surveyed were families whose children
      were hospitalized due to pneumonia. RESULTS: The results revealed that only 16
      items of the instrument demonstrated evidence of acceptable constructs of
      reliability and validity. The study recommends further studies that add other
      potential constructs related to family satisfaction.

PMID- 30115346
TI  - Nurses challenging to terminate irrelevant treatment prior to end of life
      patient.
AB  - Observations were done since 2008 in hospital, community concluded that end of
      life patients, and families did not understand how to respond to advance
      treatment. Besides, there were no similar standard of procedure applied into
      patients. There were some doctors told the families about patients' conditions
      and some did not. Moreover, some families understood that patients' condition
      could not be cured, but in dying process, the physicians suggested to be treated
      in an intensive care unit. In this situation, the families did not have any
      choice instead of to follow the physician suggestion. Indonesian's health care
      system that embrace doctor's domination over decision-making on patient treatment
      exists, although nurse has their own skills, function and knowledge that need to
      be incorporated in the treatment plan. On the other hand, nurses do not have
      initiatives to challenge this system in health care structure. This study refers
      to a Philosophical Carol Gilligan Theory, and Bakker & Zubair Qualitative Method
      of Philosophical Research. The results were divided into 2 groups: firstly were
      the nurses who were mostly women had their limitation to raise up their
      profession, and secondly, the basic nurses education was insufficient to
      encounter the doctors.

PMID- 30115347
TI  - Chronic Heart Failure Patients' Perceptions on their Palliative Care Needs.
AB  - OBJECTIVE: The aim of this study was to investigate the perceptions of patients
      with chronic heart failure regarding palliative care needs. METHOD: The study
      used a qualitative design. Five patients with chronic heart failure (New York
      Heart Association functional classes III or IV) were interviewed in inpatient
      unit at the main referral government hospital in Indonesia. Data was analyzed
      using content analysis. RESULTS: Patients reported dyspnea and fatigue as the
      most common signs and symptoms of chronic heart failure. Psychologically,
      patients experience fear and believe that the disease is the most serious
      illness. Declining body functions and quality of life are the reasons chronic
      heart failure patients need palliative care. Professional treatment, end-of-life
      care, information, support, and motivation are identified as the needs of
      patients in palliative care. CONCLUSIONS: The findings provide valuable
      information for health care professionals about the needs of patients with
      chronic heart failure in relation to palliative care.

PMID- 30115348
TI  - The experience of people with mental disorders in social function adaptation
      after suffering from pasung.
AB  - OBJECTIVE: Pasung is a physical restraint or confinement of people with mental
      disorders performed by non-professional members of society. It can cause various
      effects on people with mental disorders. Pasung can affect the people adaptation
      to functioning socially in society following the release from pasung. The purpose
      of this study was to describe the experience of people with mental disorders,
      post-pasung, in adapting to society METHOD: This was a qualitative study, using a
      descriptive phenomenological approach. Purposive sampling was used to select the
      participants. Data were obtained though in-depth interviews with seven
      participants, and the data were analyzed by using Colaizzi's method. RESULTS:
      Pasung has a physical and psychosocial impact on people with mental disorders in
      adapting to society. The results of the study can be summarized by four themes:
      a) withdrawal from others as an initial manifestation of release from pasung; b)
      biopsychosocial changes after pasung that act as an impediment to performing a
      social function; c) improved social function through the optimization of support
      systems, and d) satisfaction with life as a result of social adaptation.
      CONCLUSIONS: Increased social support is needed to optimize the social function
      of people with mental disorders, post-pasung.

PMID- 30115349
TI  - Relationship between maternal knowledge of balanced nutritional guidelines and
      snack food selection by school-aged children at school.
AB  - OBJECTIVE: Eating behavior of school-aged children was dominated by street foods.
      The aim of the present study was to examine the relationship between maternal
      knowledge of balanced nutritional guidelines and snack food selection by school
      aged children during school hours. This also aims to describe each demographic
      data and level of mother's knowledge. METHOD: This study conducted a descriptive
      correlational design. The participants were selected using simple random sampling
      technique, consisting of 4th and 5th grade elementary school children and their
      mothers in SDN Tugu 4, Depok City, Indonesia. Demographic data were also taken
      for each. The instruments used the Food Frequency Questionnaire and questions
      about the balanced nutritional guidelines. Statistical analysis conducted a
      univariate (descriptive) and bivariate (relationship) analysis. Bivariate
      analysis used independent t test and ANOVA test, using (P value < 0.05) to
      indicate a significant relationship. RESULTS: A total of 118 elementary students
      and their mothers participated. The results showed that there was no significant
      relationship between maternal knowledge of balanced nutritional guidelines and
      snack food behavior by children during school hours (P = 0.108). Level of
      knowledge of the mothers on balance nutritional guidelines was dominantly
      moderate (58.4%). CONCLUSIONS: Parents no longer became a major factor
      influencing the child's diet. Peers have more influence on the diet of children
      this age. This study points to the importance of education on healthy and safe
      snack foods for school-aged children in collaboration with peers, parents,
      teachers, and food vendors at school.

PMID- 30115350
TI  - Arbi Care: an innovative educational game to increase healthy behavior in
      diarrhea prevention among preschoolers.
AB  - Innovation is needed to improve healthy behaviors of children in order to prevent
      diarrhea. Education through games is widely recommended as a way to change
      behavior in children. This study describes the process of developing an
      educational game to increase healthy behaviors of preschool children. This study
      used research and development design techniques with four stages, including:
      define, design, develop, and disseminate. Observation sheets were used to assess
      the effectiveness of the game in educating children. The process of developing
      this educational game included several phases: 1) exploration of the
      characteristics of games favored by children; 2) design of the intervention based
      on games preferred by children; 3) validation of the game prototype by experts
      and testing of the game by preschool children, and 4) revision of the game in
      order to obtain a game focused on diarrhea prevention that can be used as a
      behavioral health intervention. Results showed that in testing of the game by ten
      preschool were able to play and understand the message of the game 92% of the
      time. The results showed that the Arbi Care game can be used as a learning device
      to increase healthy behavior in preschool children.

PMID- 30115351
TI  - Effectiveness of Psychological Adaptation Model of Mental Health Nursing for
      nurse survivors experiencing post-earthquake disaster post-traumatic stress
      syndrome.
AB  - OBJECTIVE: The study to assess the effectiveness of psychological adaptation
      model of mental health nursing for nurse survivors experiencing post-earthquake
      post-traumatic stress syndrome (PTSS). METHOD: This study used a quasi
      experimental pre- post-test without control group method. Respondents amounted to
      42 people who have been screened for PTSS. Research took place in a district in
      West Java. Research instrument consisted of: 1) questionnaire for respondent's
      characteristics and the skills of nurses, and 2) psychological adaptation model
      of mental health nursing intervention in the form of modules. Data collected was
      analyzed using bivariate analysis namely the t test dependent. RESULTS: Nurse
      survivors experienced increased ability in areas including analysis of self
      awareness, communication or interaction, coping mechanisms, and intrinsic
      motivation after undertaking the PTSS intervention. Women were more likely to
      experience PTSS than men. CONCLUSIONS: The model can be used for nursing theory
      development, and as disaster management algorithms. The model is useful for
      training programs, in the form of certification of nurse expertise, and improve
      the ability of nurses to help themselves and others.

PMID- 30115352
TI  - The experience of restraint-use among patients with violent behaviors in mental
      health hospital.
AB  - OBJECTIVE: Patients with violent behavior can harm themselves, others and
      environment. It can be an indicator for mental health hospital admission. Violent
      behaviors can be characterized by verbal and physical attacks demonstrated by the
      individuals intensively. Management of violent behaviors in hospital often uses
      restraint, but it has physical and psychological effects. This study aimed to
      explore experience of restraint use among patients with violent behaviors in
      mental health hospital. METHOD: To gain deep understanding related to the
      patients' experiences, this study used a qualitative design with a
      phenomenological approach. Purposive sampling was employed to find patients who
      were restrained during their hospitalization. The number of participants in this
      study was 8 participants. The data were analyzed with Colaizzi's method. RESULTS:
      Patients with violent behavior, specifically with physical restraint during their
      hospital-ization had negative impacts on patients. The results of this study were
      described in three themes: 1) aggressive behavior as one of the main reason of
      restraint; 2) professional healthcare supports during the restraint use, and 3)
      physical and psychosocial impact of the restraint use. CONCLUSIONS: The impact of
      restraint is related to human right violations and ethical dilemma. The process
      of decision-making for employing restraint, especially in relation to violent
      behavior management, requires a consideration of the rights of the patient. Every
      individual has the right of self-determination, liberty, security and physical
      integrity.

PMID- 30115353
TI  - The influence of assertiveness training on depression level of high school
      students in Bengkulu, Indonesia.
AB  - OBJECTIVE: The research identified the influence of assertiveness training
      against teenage depression in high scholars in Kepahiang Regency, Bengkulu,
      Indonesia. METHOD: This study used a quasi-experiment approach with pre-test and
      post-test design and a control group. Eighty students were engaged through simple
      random sampling. RESULTS: The study found the frequency of depression in
      teenagers and considered the effect of assertiveness training. 14.10 teens were
      counted as depressed before assertiveness training provision, while the post
      training average was 7.98 (p = .000). Assertiveness training had a significant
      effect on the prevalence of depression in the intervention group. CONCLUSIONS:
      The study recommends schools to cooperate with health services to increase mental
      health programs such as building peer groups, delivering assertiveness training,
      and teaching stress management to prevent depression in teenagers.

PMID- 30115354
TI  - Grandparents' roles and psychological well-being in the elderly: a correlational
      study in families with an autistic child.
AB  - OBJECTIVE: The purpose of this study was to explore the family roles and
      psychological well-being of grandparents who are caregivers of grandchildren with
      autism spectrum disorders. METHOD: The study used quantitative methods with a
      correlational design. A self-administered questionnaire was used as an instrument
      to measure the variables of psychological wellbeing and the grandparenting role.
      This research involved 108 grandparents from Semarang, Jepara and Kendal,
      obtained through a quota-purposive sampling technique. Quantitative data analysis
      was based on simple regression analysis. RESULTS: The study results showed rxy=
      0.397; P = .000 (P < .05), which indicates a positive and significant correlation
      between the role played by grandparents and their psychological well-being.
      CONCLUSIONS: The test results indicate a significant correlation between the
      roles of grandparents and their psychological well-being. The greater the role
      played by grandparents, the higher psychological well-being they experienced, and
      vice versa. Grandparents play an important role in families where there is a
      child with autism; they take care of the child when the parents are not at home,
      help with the cost of therapy, and take care of them when sick.

PMID- 30115355
TI  - Prevalence and association between triglyceride level and lifestyle factors among
      Malay obese class I and II adults.
AB  - OBJECTIVE: Hypertriglyceridemia is an independent risk factor for cardiovascular
      diseases. This study aimed to determine the prevalence and association of
      triglyceride level and lifestyle factors among Malay obese class I and II adults.
      METHOD: This is a cross-sectional study of 65 Malay obese class I and class II
      adults aged 20-62 years (21 male, 44 female) from sub-urban areas of Malaysia.
      Overnight fasting venous blood samples were obtained to determine the
      triglyceride level (mmol/L). Subjects were classified into either normal or
      elevated triglyceride level groups based on the triglyceride level (normal < 1.6
      mmol/L, elevated > 1.7 mmol/L). Unhealthy lifestyle behaviors, defined as smoking
      status, hours per day spent on sitting passively and sitting with active motion,
      and the amount of saturated fat, mono-unsaturated and polyunsaturated fat from
      dietary intake, were measured from 24-h dietary intake and physical activity
      recall. We compare the variables of unhealthy lifestyle behaviors between
      subjects with normal and elevated triglyceride level using independent samples t
      test. RESULTS: Among 65 obese class I and II adults, 16 subjects (24.6%) were
      found to have elevated triglyceride levels (mean +/- standard deviation of body
      mass index 31.89 +/- 3.29 kg/m2). There are significant differences between
      subjects having normal and elevated triglyceride level with gender, marital
      status, the number of children, smoking status, weight and monounsaturated fat
      intake (all P-values < .05). CONCLUSIONS: The findings of this study highlighted
      elevated triglyceride level in obese adults might be influenced by unhealthy
      lifestyle behaviors. We suggest that lifestyle modification intervention is
      appropriate to prevent cardiovascular disease among Malay obese class I and II
      adults.

PMID- 30115356
TI  - The life during adolescence in the perspective of ex-drug users in Indonesia.
AB  - OBJECTIVE: Substance misuse tends to be higher among adolescents. This study
      explored the experience of substance misuse during adolescence. METHOD: This
      qualitative study employed a descriptive phenomenological approach. A purposive
      sampling was adopted to involve 8 former drug users. Data were analyzed using
      Collaizi's method. RESULTS: This study generated the following themes: 1) smoking
      as an initial exposure to substance use; 2) substance use is aimed to explore
      self-identity; 3) lack of information and education about substance and drug use
      in the family and community; 4) the quality of family relationships influencing
      substance misuse, and 5) stigmas related to substance abuse. CONCLUSIONS: Smoking
      precedes other substance use among adolescents. To be socially accepted,
      adolescents tend to take risky decisions. Inadequate knowledge of drugs and poor
      family relationships can contribute to substance abuse. Nevertheless, inadequate
      familial or community support to encourage drugs users in rehabilitative programs
      is also problematic. Moreover, drugs users are often stigmatized and socially
      isolated even after becoming clean.

PMID- 30115357
TI  - Family Experience in Treating Children with Chronic Renal Failure Undergoing
      Hemodialysis Therapy.
AB  - OBJECTIVE: Children who enter phase 5 of chronic renal failure need hemodialysis
      as a therapy. In undergoing hemodialysis, children experience various physical
      and psychosocial problems. Parents, as caregivers, are required to be at their
      children's side to overcome these problems. This study aimed to explore the
      experience of families in caring for children with chronic renal failure
      undergoing hemodialysis therapy. METHOD: This research method used a descriptive
      phenomenological approach with in-depth interviews of seven participants.
      Participants were families who had a child with chronic kidney failure undergoing
      hemodialysis in a top referral hospital in Jakarta for at least one month. Data
      were analyzed using the Colaizzi technique. RESULTS: Five themes were identified:
      a) families' response to child care; b) families' coping strategies; c) the
      impact of child care for families; d) family support, and e) families'
      perceptions of changes in children undergoing hemodialysis therapy. These five
      themes highlighted how hemodialysis for children affected family life.
      CONCLUSIONS: Family experiences in treating children with chronic renal failure
      influence their life in economical, physical, psychological, intellectual, and
      religious ways.

PMID- 30115358
TI  - Does open or closed endotracheal suction affect the incidence of ventilator
      associated pneumonia in the intensive care unit? A systematic review.
AB  - OBJECTIVE: To compare closed and open endotracheal suction system in relation to
      ventilator-associated pneumonia in adult intensive care unit patients METHOD:
      Systematic review. RESULTS: Of the 18 eligible studies identified through the
      search strategy, only 5 studies were included in the review. The two endotracheal
      suction systems show no differences in the incidence of ventilator-associated
      pneumonia (5 trials: odds ratio [OR], 0.92; Mantel-Haenszel [M-H], fixed; 95%
      confidence interval [95%CI], 0.72-1.18) or mortality rates (3 trials: OR, 0.89; M
      H, fixed; 95%CI, 0.62-1.28). CONCLUSIONS: Results from 5 studies showed that
      suctioning with either closed or open endotra-cheal suction did not have an
      effect on the incidence of ventilator-associated-pneumonia or mortality rates.
      Therefore, more rigorous and large-scale research is needed for further
      evaluation.

PMID- 30115359
TI  - The influence of health training on teachers and students' knowledge of
      adolescent reproductive health.
AB  - OBJECTIVE: There are many adolescent health problems in Indonesia, particularly
      problems related to reproductive health. If adolescent reproductive health is not
      given adequate attention, this can lead to other adolescent health problems.
      Aside from parents, school staff also plays an important role in overcoming this
      health concern because educational staff is closer to adolescents than their
      parents. Teachers and friends can act as a resource for adolescents, providing
      them with reproductive health information. Therefore, the knowledge level of
      those at school, such as teachers and peer, about adolescent reproductive health
      is important. This research aims to determine the effects of adolescent
      reproductive health training on teacher and peer knowledge. METHOD: This research
      used an experimental design. A purposive sampling technique was used to recruit
      26 students and 24 teachers, and a pretest and posttest were administered to one
      group without control group and then analyzed by Wilcoxon test. RESULTS: The
      results showed that health training had a significant effect on teacher and peer
      knowledge with P < alpha (0.05). CONCLUSIONS: It can be concluded that training
      on adolescent reproductive health for teachers and peers can be implemented at
      every school to increase their knowledge and skills and to prevent unsafety
      adolescent sexual behavior.

PMID- 30115360
TI  - Effectiveness of Lafiska exercise on risk of fall, balance, and health status in
      the elderly.
AB  - This study aims to investigate the effectiveness of Latihan Fisik Lansia "elderly
      physical exercise" on the balance status, risk of fall, and health status of
      institutionalized older adults. A quasi-experimental design was applied measuring
      pre-test and post-test outcomes in a control group to determine the effectiveness
      of the intervention in the interventional group. Eighty participants from Panti
      Sosial Tresna Werdha Budi Mulia 1 Cipayung were divided into an inter-ventional
      group with 39 older adults (70.3 +/- 8.13 years) and a control group with 41
      older adults (69.88 +/- 8.71 years). Trained facilitators guided the exercise
      during 16 sessions over eight weeks, each having duration of 50 min, with a small
      group consisting of 10-12 participants. This study used Morse Fall Scale to
      measure risk of fall, Berg Balance Scale to measure balance status, and SF-12 to
      measure health status. Lafiska had an impact on lowering risk of fall, enhancing
      balance status, and enhancing health status (P value <.0001). Lafiska is a viable
      exercise option for older adults with independent mobility, as well as older
      adults with assistive devices.

PMID- 30115361
TI  - Family stress experience in dealing with child victims of sexual violence.
AB  - OBJECTIVE: Stress is one of the responses experienced by families with child
      victims of sexual violence. The purpose of this study was to explore in depth the
      stress experienced by families dealing with child victims of sexual violence.
      METHOD: This qualitative study employed the phenomenology approach. A purposive
      sample of six families participated in the study. Data were analyzed using
      Colaizzi's method. RESULTS: This study discussed the experience of family with
      children who are victims of sexual violence. This study generated the following 5
      themes: 1) sexual violence and the subsequent behavior changes in children as a
      source of family stress; 2) Family stress as a response to changes in the family
      process; 3) social support as sources of the family's strengths; 4) spiritual
      activities for coping with stress, and 5) parenting changes as a family learning
      and evaluation. CONCLUSIONS: Results suggested the development of the School
      Mental Health Unit to help families, and the community, identify and prevent
      sexual violence. In addition, the School Mental Health Unit would be a useful
      source for students who experience sexual violence to function well at school.

PMID- 30115362
TI  - The experience of older people living in nursing home (Panti Wredha) in DKI
      Jakarta, Indonesia.
AB  - Inability to fulfil daily needs and natural aging process will affect both health
      and life satisfaction among older people. Services to older people in nursing
      home may be affected when cooperation between nurse, caregiver and older people
      are not optimal. Hence, the cooperation between them must be optimized to enhance
      services and maintain quality of life among the older people. The aim of this
      study was to develop a partner model between nurse, caregiver and older people in
      nursing home, Panti Wredha in Jakarta, to improve caring behavior, health status,
      satisfaction and quality of life of older people. This study's operational method
      consisted of three phases: (I) exploration phase, (II) model development phase,
      and (III) model trial phase to assess the model effectiveness. The first year was
      phase I and II. The second year was phase III model trial to assess the model
      effectiveness. This article will report the phase I findings. Qualitative design
      with a descriptive phenomenology approach was used. The population was older
      people living in Nursing Home (Panti Wredha) in Jakarta. The sample for phase I
      was selected according to some criteria until data saturation was achieved: eight
      older people. Data were collected using face-to-face interview to older people.
      Data were analyzed using Collaizi method. The result of 11 themes (older people).
      This result will be used further for development of model and module, and will
      test by readability and expert test.

PMID- 30115363
TI  - Expansion sphincter pharyngoplasty: Usefulness of DISE.
AB  - OBJECTIVES: The aim of this study was first to present the indications and
      results using expansion sphincter pharyngoplasty to treat obstructive sleep
      apnoea-hypopnoea syndrome (OSAHS). And second, to compare the findings of drug
      induced sleep endoscopy (DISE) before and after the surgery. MATERIAL AND
      METHODS: The study design was a prospective cohort of patients surgically treated
      between 2015 and 2016. All patients were diagnosed with mild to severe
      obstructive sleep apnoea and did not tolerate CPAP. All had pre- and post-surgery
      DISE and polysomnography. The inclusion criteria were age, between 18 years and
      70 years, small tonsils (sizes 1 and 2), Friedman II and III clinical stage, and
      lateral collapse in preoperative DISE. We performed surgery to the palate only,
      using expansion sphincter pharyngoplasty. RESULTS: Seventeen patients were
      included, 52.94% had severe OSAHS. Average age was 42 years, average body mass
      index was 28. The surgical success rate according to Sher criteria was 82.35%.
      41.17% had a postoperative apnoea-hypopnoea index of less than 10. Seventy-five
      percent of the patients had no further need for CPAP. CONCLUSION: Expansion
      sphincter pharyngoplasty is a safe technique for treating OSAHS, in patients with
      small tonsils, Friedman grade I and II and collapse of lateral walls in DISE, in
      the absence of multilevel collapse. The postoperative DISE showed improvement of
      the lateral collapse was achieved with the expansion.

PMID- 30115364
TI  - CT spectral parameters and serum tumour markers to differentiate histological
      types of cancer histology.
AB  - AIM: To evaluate lung cancer histology type using computed tomography (CT)
      spectral quantitative parameters combining with serum tumour markers. MATERIALS
      AND METHODS: Patients with suspicious lung cancer underwent CT spectral imaging
      and serum tumour markers. CT spectral quantitative parameters including
      attenuation value, the slope of spectral curve (lambda), iodine concentration,
      water concentration, and effective atomic number (Zeff) were acquired. Serum
      levels of tumour markers including carcinoembryonic antigen (CEA), neuron
      specific enolase (NSE), squamous cell carcinoma antigen (SCC-Ag), and cytokeratin
      fragment CYFRA21-1 were also obtained. All the values were compared among
      different histological types of lung cancer. The diagnostic efficiencies of serum
      tumour markers, CT spectral parameters, and a combination of them were computed
      by statistical analysis. RESULTS: CEA and NSE levels were higher in
      adenocarcinoma and neuroendocrine tumour, respectively, while SCC-Ag and CYFRA21
      1 levels were higher in squamous cell cancer. There was no significant difference
      in attenuation among the groups (p>0.05), whereas lambda in the arterial phase,
      and Zeff and IC in both the arterial and venous phases were significantly
      different among groups (p<0.05). According to the area under the receiver
      operating characteristic (ROC) curve (AUC) and Youden's index, the diagnostic
      efficiency of serum tumour markers were higher than that of CT spectral
      parameters. Moreover, AUCs of combined serum and CT indicators were larger than
      that of combined serum markers and combined CT spectral parameters between
      squamous cell cancer and adenocarcinoma as well as between squamous cell cancer
      and neuroendocrine tumour. CONCLUSION: CT spectral quantitative parameters and
      serum tumour markers are valuable in evaluating histological types of lung
      cancer. In combination they can significantly improve diagnostic efficiency.

PMID- 30115365
TI  - Clinical manifestations and imaging findings of thrombosis of developmental
      venous anomalies.
AB  - AIM: To determine clinical manifestations, imaging findings and outcome of
      patients with thrombosed developmental venous anomalies (DVAs). MATERIALS AND
      METHODS: The radiology database was searched retrospectively for thrombosed DVAs
      between 01/01/2000 to 07/01/2016. Demographic variables, associated risk factors,
      clinical manifestations, imaging findings, treatments, and follow-up were
      recorded. RESULTS: Six patients were found (four female and two male; age range
      16-45 years with mean age, 21.3 years). The most common clinical presentation was
      headaches followed by neurological deficits and seizures. Venous infarction,
      parenchymal haemorrhage, venous congestive oedema were noted as the radiological
      findings. Clinical outcome was favourable in all patients with complete recovery
      or persistence of mild neurological symptoms. CONCLUSION: Thrombosed DVAs may
      occur under rare circumstances, which lead to variable symptoms. Familiarity with
      this entity and early recognition of associated findings including venous
      infarction, parenchymal haemorrhage, and venous congestive oedema would help
      early diagnosis and prompt treatment.

PMID- 30115366
TI  - [Reprint of: Treatment of patients with inoperable stage III or stage IV
      melanoma. Societe francaise de dermatologie].

PMID- 30115367
TI  - The multiple arrhythmia dataset evaluation database (M.A.D.A.E.).
AB  - The convergence between wearable and medical device technologies is a natural
      progression. Miniaturization has allowed the design of small, compact monitoring
      systems that can record physiological signals over longer periods of time. Thus,
      the potential for these devices to expand the understanding of disease
      progression and patients' clinical status is very high. The accuracy of these
      devices, however, is dependent upon the computer algorithms utilized in the
      analysis of the large volume of physiological data monitored and/or recorded by
      the devices. Automated interpretation of the data by these new technologies,
      therefore, necessitates closer examination by regulatory organizations. The
      current requirements for the validation of novel Ambulatory ECG (A-ECG)
      annotation algorithms are based on the AAMI/ANSI-EC57 and IEC60601-2-47 Standard.
      These standards are being updated, but they rely on a very limited set of
      digitized ECG recordings from a couple of ECG databases built in the first half
      of the 70's. These reference signals are obsolete. We are developing a validation
      tool for computerized methods designed to detect and monitor cardiac activities
      based on body-surface ECGs. We will rely on a set of existing digital high
      resolution 12-lead A-ECG recordings acquired in cardiac patients and healthy
      individuals. These ECG signals include a large and unique set of
      electrocardiographic events. This tool is being qualified by the Center for
      Devices and Radiological Health of the United States Food and Drug Administration
      (FDA) as a Medical Device Development Tool (MDDT). This document provides
      insights into the design of the M.A.D.A.E. database, its functionalities, and its
      ultimate role in enabling the next generations of automatic interpretation of ECG
      signals.

PMID- 30115368
TI  - Accurate detection of atrial fibrillation and atrial flutter using the
      electrocardiomatrix technique.
AB  - BACKGROUND: Atrial fibrillation (AFIB) and atrial flutter (AFL) are two common
      cardiac arrhythmias that predispose patients to serious medical conditions. There
      is a need to accurately detect these arrhythmias to prevent diseases and reduce
      mortality. Apart from accurately detecting these arrhythmias, it is also
      important to distinguish between AFIB and AFL due to differing clinical
      treatments. METHODS: In this study, we applied a new technology, the
      electrocardiomatrix (ECM) invented in our lab, in detecting AFIB and AFL in human
      patients. ECM converts 2D ECG signals into a 3D color matrix, which renders
      arrhythmia detection intuitive, fast, and accurate. Using ECM, we analyzed the
      ECG signals from the online MIT-BIH Atrial Fibrillation Database (PhysioNet), and
      compared our ECM-based results to manual annotations based on ECG by physicians.
      RESULTS: Results demonstrate that ECM and PhysioNet annotations of AFIB and AFL
      agree more than 99% of the time. The sensitivities of the ECM for AFIB and AFL
      detection were 99.2% and 98.0%, respectively, and the specificities of the ECM
      for AFIB and AFL were both at 99.8% and 99.8%. CONCLUSIONS: This study
      demonstrates that ECM is a reliable method for accurate identification of AFIB
      and AFL.

PMID- 30115369
TI  - Gastric glomus tumour: A challenge in the preoperative diagnosis of stomach
      subepithelial lesions.

PMID- 30115370
TI  - Intravenous Lipid Emulsions in Veterinary Clinical Toxicology.
AB  - Use of intravenous lipid emulsion (ILE) as an antidote for severe cardiotoxicity
      and neurotoxicity has expanded in the veterinary world in the past decade.
      Despite advances in understanding of potential mechanisms of action of antidotal
      ILE, knowledge gaps remain in efficacy, appropriate dosing rates for various
      toxicants, and potential adverse reactions. Use of ILE in management of toxicoses
      of veterinary patients should be considered investigational, and should not be
      first-line treatment of most toxicoses, especially where established treatment
      protocols have good likelihood of positive outcomes. Use of ILE in veterinary
      toxicology cases requires judicious assessment of individual cases and proper
      informed consent of clients.

PMID- 30115371
TI  - Melatonin and mitochondrial dysfunction are key players in the pathophysiology of
      sepsis.

PMID- 30115372
TI  - Investigation of the nutritional, functional and technological effects of the
      sourdough fermentation of sprouted flours.
AB  - In recent years, recommendations on whole grains consumption have been added to
      the overall dietary guidelines of many countries around the world. Despite the
      many benefits on human health, whole grains contain several anti-nutritional
      factors which decrease their nutritional quality leading to a poor use in human
      diet. Here, an integrate biotechnological approach, combining germination and
      sourdough fermentation with selected lactic acid bacteria, was set-up in order to
      improve the functional and nutritional quality of wheat, barley, chickpea, lentil
      and quinoa grains. Sourdough fermentation with Lactobacillus rossiae LB5,
      Lactobacillus plantarum 1A7 and Lactobacillus sanfranciscensis DE9 further
      enhanced the nutritional and functional features of sprouted flours by means of
      increased peptides, free amino acids and gamma-aminobutyric acid concentrations,
      and decreased phytic acid, condensed tannins, raffinose and trypsin inhibitory
      activity. Sensory appreciable wheat breads fortified with the fermented sprouted
      flours were manufactured and characterized, showing high protein digestibility
      and low starch availability.

PMID- 30115373
TI  - Exploitation of autochthonous Tuscan sourdough yeasts as potential starters.
AB  - The increasing demand for healthy baked goods boosted studies on sourdough
      microbiota with beneficial metabolic traits, to be used as potential functional
      starters. Here, yeast populations of traditional sourdoughs collected from four
      Tuscan bakeries were investigated. Among 200 isolated strains, 78 were randomly
      selected and molecularly characterized. Saccharomyces cerevisiae was dominant,
      representing the only species detected in three out of the four sourdoughs. The
      fourth one harbored also Kazachstania humilis. Inter-delta regions analysis
      revealed a high intraspecific polymorphism discriminating 16 biotypes of S.
      cerevisiae isolates, which clustered based on their origin. Representative
      isolates from each biotype group were individually used to ferment soft and durum
      wheat flour, aiming at evaluating their pro-technological, nutritional and
      functional features. During fermentation under standardized conditions, all
      strains were able to grow of ca. 2 log cycles, but only S. cerevisiae L10Y, D18Y
      and D20Y had a significantly shorter latency phase in both flours. Overall, the
      highest volumes were reached after 16 h of fermentation in both soft and durum
      fermented dough. S. cerevisiae D2Y produced the highest dough volume increase. K.
      humilis G23Y was the only strain able to increase the total free amino acids
      concentration of the doughs. Overall, values of phytase activity were
      significantly higher in durum compared to the corresponding soft fermented dough.
      K. humilis G23Y and S. cerevisiae D20Y, D24Y showed a threefold higher phytase
      activity than spontaneously fermented control, and the highest concentration of
      total phenols. Almost all the strains led to increases of antioxidant activity,
      without significant differences among them. Investigations on the resistance of
      the strains to simulated gastric and intestinal conditions, that is considered a
      pre-requisite for the selection of probiotics, revealed the ability to survive in
      vitro by many of the strains considered. This study proposed the best performing
      yeast strains selected among autochthonous sourdough yeasts based on their pro
      technological, nutritional and functional traits to be used as starters for
      making sourdough baked goods or functional cereal-based beverages. Although some
      yeast strains combined several technological and nutritional traits, the
      association of more selected strains seemed to be a requisite to get optimal
      sourdough characteristics.

PMID- 30115374
TI  - Communities of Niche-Optimized Strains: Small-Genome Organism Consortia in
      Bioproduction.
AB  - Bacterial genome reduction is a common phenomenon in nature that has also
      inspired several projects with biotechnologically relevant organisms. In many
      cases, however, no performance improvements with the streamlined chassis were
      obtained. A comparative analysis of natural and synthetic reduced genomes and
      their corresponding ecological niches reveals that: (i) deleting expressed genes
      can lead to noticeable energy conservation usable for improved biomass or product
      synthesis; and (ii) the simplified strains depend on the environment (e.g.,
      another community member) to complement deleted functions. Based on this
      analysis, we introduce the concept of Community of Niche-optimized Strains
      (CoNoS) as an alternative strategy to generate superior biotechnological
      production processes.

PMID- 30115375
TI  - Single-Molecule Sequencing: Towards Clinical Applications.
AB  - In the past several years, single-molecule sequencing platforms, such as those by
      Pacific Biosciences and Oxford Nanopore Technologies, have become available to
      researchers and are currently being tested for clinical applications. They offer
      exceptionally long reads that permit direct sequencing through regions of the
      genome inaccessible or difficult to analyze by short-read platforms. This
      includes disease-causing long repetitive elements, extreme GC content regions,
      and complex gene loci. Similarly, these platforms enable structural variation
      characterization at previously unparalleled resolution and direct detection of
      epigenetic marks in native DNA. Here, we review how these technologies are
      opening up new clinical avenues that are being applied to pathogenic
      microorganisms and viruses, constitutional disorders, pharmacogenomics, cancer,
      and more.

PMID- 30115376
TI  - Different involvement of the MAPK family in inflammatory regulation in human
      pulmonary microvascular endothelial cells stimulated with LPS and IFN-gamma.
AB  - Pulmonary endothelial injury is central in the pathogenesis of acute lung injury
      (ALI). The MAPK signaling cascades are generally thought to be involved in the
      molecular mechanism underlying the ALI development, but their roles in pulmonary
      endothelial injury is poorly understood. We thus examined the involvement of the
      MAPK family member in inflammatory responses of human pulmonary microvascular
      endothelial cells (HPMVECs) stimulated with LPS and IFN-gamma. HPMVECs were found
      to exhibit the upregulation of expression of Toll-like receptor 4 by IFN-gamma,
      resulting in potentiation of inflammatory cytokine release by LPS stimulation.
      All MAPKs, ERK1/2, JNK, and p38, were activated by simultaneous stimulation with
      LPS/IFN-gamma. JNK activation in cells stimulated with LPS/IFN-gamma was
      significantly potentiated by the two different p38 inhibitors, SB203580 and
      RWJ67657, suggesting the negative regulation of JNK activation by p38 in HPMVECs.
      The mRNA and protein expression levels of ICAM-1 were eliminated by the JNK
      inhibitor, suggesting that ICAM-1 expression is positively regulated by JNK. The
      p38 inhibitor significantly enhanced ICAM-1 expression. ERK1/2 activation was not
      responsible for the LPS/IFN-gamma-induced ICAM-1 upregulation in HPMVECs. THP-1
      monocyte adhesion to HPMVECs under LPS/IFN-gamma stimulation was inhibited by the
      JNK inhibitor and enhanced by the p38 inhibitor. We conclude that, in HPMVECs
      stimulated with LPS/IFN-gamma, JNK mediates ICAM-1 expression that can facilitate
      leukocyte adherence and transmigration, while p38 MAPK negatively regulates the
      upregulation of ICAM-1 through inhibition of JNK activation.

PMID- 30115377
TI  - High frequency of anti-protein Z antibodies in patients with anticardiolipin
      antibodies.
AB  - Protein Z (PZ) is a vitamin K-dependent protein involved in the down-regulation
      of coagulation by forming a complex with the protein Z-dependent protease
      inhibitor. The complex inhibits the activated factor X on phospholipid surface.
      Presence of anti-PZ (aPZ) antibodies was first described in women with
      pathological pregnancies but the significance of aPZ antibodies in other
      pathological situations was poorly studied. In this work we analyzed the
      frequency of aPZ antibodies in a series of 86 consecutive patients with
      anticardiolipin (aCL) antibodies and studied the association of aPZ with other
      antiphospholipid (aPL) antibodies [lupus anticoagulant (LAC) and anti-beta2GP-1
      antibodies] and the clinical signification of these aPZ antibodies in term of
      thrombosis or fetal loss. Anti-PZ antibodies (IgG and IgM) were detected using
      commercially available ELISA assays. The frequency of aPZ antibodies was 40.7% in
      the patient group versus 6.8% in a group of 59 healthy volunteers (p < 0.0001).
      The frequency of aPZ antibodies significantly increases (p < 0.05) in patients
      with a double or triple positivity of aPL antibodies and a higher frequency of
      aPZ antibodies was observed in patients with LAC (57.7%) than in patients without
      LAC (25.6%, p = 0.02). There were no significant differences in aPZ antibodies
      frequency between patients with and without thrombotic events. Interestingly,
      among the 8 women with recurrent foetal losses, aPZ antibodies were observed in 7
      cases, in agreement with previous observations suggesting that aPZ antibodies may
      be associated with obstetrical complications.

PMID- 30115378
TI  - Correlations Among Objectively Measured Impairment, Outcome Classification
      Systems, and Subjectively Perceived Disability After Flexor Tendon Repair.
AB  - PURPOSE: Any loss of range of motion of the finger after flexor tendon repair is
      an impairment of function, but to what extent it causes disability is not
      properly understood. The aim of this study was to assess the correlation between
      perceived function (disability) and objectively measured loss of function
      (impairment), to understand what impairments are meaningful to patients. METHODS:
      We assessed 49 patients who underwent flexor tendon repair an average of 38
      months after repair. We measured the perceived function with the visual analog
      scale, the 4-step rating scale (poor, fair, good, or excellent), and the
      Disabilities of the Arm, Shoulder, and Hand (DASH) score. The objective
      measurement of impairment included active range of motion at each joint, total
      active motion, grip strength, and 2-point discrimination. We also converted range
      of motion into 4 categories (poor, fair, good, and excellent) following
      guidelines from 3 different classification systems (American Society for Surgery
      of the Hand, Strickland-Glocovac, and revised Strickland). We used Spearman rho
      and linear regression to assess the correlation. RESULTS: Active range of motion
      at the distal interphalangeal joint had a strong correlation (rho = 0.61) and
      total active range of motion of the finger joints had a moderate correlation (rho
      = 0.45) with perceived function measured using the visual analog scale and DASH
      score. Other measured impairments did not correlate with perceived function.
      Objective classification categories also did not correlate with the patient's own
      assessment. CONCLUSIONS: Our results validate the use of range of motion and the
      DASH questionnaire in assessing flexor tendon repairs. Classification of angular
      measurement according to the tested systems does not reflect the patient's
      perspective; it limits the precision of the measurement and adds little value to
      the measurement itself. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic IV.

PMID- 30115379
TI  - Runx1 promotes satellite cell proliferation during ischemia - Induced muscle
      regeneration.
AB  - RUNX1 is a transcription factor that is not expressed in uninjured muscles, but
      can be detected in denervated muscles, suggesting a role of RUNX1 in muscle's
      response to injury. However, the role of RUNX1 in muscle's response to ischemia
      has not been reported. Our study showed that Runx1 is up regulated in skeletal
      muscle during ischemia reperfusion induced injury. Over-expression of Runx1 in
      C2C12 cells inhibits myogenic differentiation, but promotes proliferation of
      myoblasts. Consistent with these findings, we found that Runx1 expression was
      decreased in differentiated satellite cells. Our results indicate that Runx1
      regulates muscle regeneration by promoting proliferation of satellite cells.

PMID- 30115380
TI  - Transcriptional activation of EGFR by HOXB5 and its role in breast cancer cell
      invasion.
AB  - HOX genes are transcription factors that play important roles in body patterning
      and many cellular processes during embryonic, fetal, and adult development. Given
      their important function in normal tissues, it is reasonable to assume that
      abnormal expression of HOX genes in adults could lead to serious diseases such as
      cancer. Our previous study reported HOXB5 to be significantly up-regulated in
      breast cancer, and its expression was found to be associated with tumor cell
      proliferation and invasion. Furthermore, the epidermal growth factor receptor
      (EGFR), a cellular tyrosine kinase that plays an important role in breast cancer
      progression, was found significantly up-regulated by HOXB5 in ER-positive breast
      cancer cells. In the present study, we demonstrated that HOXB5 regulates EGFR
      expression at the transcriptional level by directly binding to its promoter
      region and promotes phosphorylation of EGFR as well as its downstream effectors.
      Patients with ER-positive breast cancer, having high co-expression of HOXB5 and
      EGFR, had poor prognosis than those with low expression. Knockdown studies
      validated a key role played by EGFR in the HOXB5-induced invasion of breast
      cancer cells. These results suggest that targeting EGFR could be an effective
      strategy to treat breast cancer in patients with high HOXB5 expression.

PMID- 30115381
TI  - Effects of calcium gluconate on lipopolysaccharide-induced acute lung injury in
      mice.
AB  - Lipopolysaccharide (LPS), which can cause acute airway inflammatory reactions,
      constitutes one of the most common substances to establish acute lung injury
      (ALI) models in mice. Studies suggest that calcium gluconate offers the
      possibility of suppressing the immune response, and this study was intended to
      explore the effects of calcium gluconate on LPS-induced ALI in mice. Mice inhaled
      with LPS were intraperitoneally injected with calcium gluconate (12.5, 25, 50
      mg/kg). IL-1beta, IL-6 and TNF-alpha levels in bronchoalveolar lavage fluid
      (BALF) were determined by ELISA. The expression of signaling proteins,
      phosphorylation extracellular regulated protein kinases (p-ERK), was detected
      using Western Blot in lung tissues. In our study, the release of inflammatory
      cytokines IL-1beta, IL-6 and TNF-alpha in BALF increased after inhalation of LPS.
      Post-treatment with calcium gluconate inhibited LPS-induced airway inflammatory
      injury and the release of inflammatory cytokines. In addition, LPS promoted the
      expression of signaling protein p-ERK while calcium gluconate was capable of
      reversing this change. Overall, calcium gluconate inhibits LPS-induced ALI in
      mice, which may take effects through the inhibition of ERK phosphorylation.

PMID- 30115382
TI  - Heat shock protein 70 and heat shock protein 90 synergistically increase
      hepatitis B viral capsid assembly.
AB  - Hepatitis B virus (HBV) infection can cause chronic liver diseases, cirrhosis,
      and hepatocellular carcinoma (HCC). Heat shock proteins (Hsps) are important
      factors in the formation of the HBV capsid and in genome replication during the
      viral life cycle. Hsp90 is known to promote capsid assembly. However, the
      functional roles of Hsp70 in HBV capsid assembly with Hsp90 have not been studied
      so far. Using microscale thermophoresis analyses and in vitro nucleocapsid
      formation assays, we found that Hsp70 bound to a HBV core protein dimer and
      facilitated HBV capsid assembly. Inhibition of Hsp70 by methylene blue (MB) led
      to a decrease in capsid assembly. Moreover, Hsp70 inhibition reduced
      intracellular capsid formation and HBV virus particle number in HepG2.2.15 cells.
      Furthermore, we examined synergism between Hsp70 and Hsp90 on HBV capsid
      formation in vitro. Our results clarify the role of Hsp70 in HBV capsid formation
      via an interaction with core dimers and in synergistically promoting capsid
      assembly with Hsp90.

PMID- 30115383
TI  - Long non-coding RNA SBF2-AS1 promotes hepatocellular carcinoma progression
      through regulation of miR-140-5p-TGFBR1 pathway.
AB  - A growing number of studies has suggested that long non-coding RNAs (lncRNAs)
      exert essential roles in the development and progression of hepatocellular
      carcinoma (HCC). However, the roles of lncRNA and its molecular mechanism in HCC
      are largely unknown. In the present study, the functions and molecular mechanisms
      of a novel lncRNA, SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1), were
      investigated in HCC tissues and cell lines. We found that the expression levels
      of SBF2-AS1 were significantly up-regulated in HCC tissues and correlated with
      poor prognosis. SBF2-AS1 knockdown could inhibit the proliferation of HCC cells
      and attenuate the development of HCC tumor in vivo. Moreover, wound healing and
      Transwell assays revealed that down-regulation of SBF2-AS1 suppressed the
      migration and invasion of HCC cells by modulating epithelial-mesenchymal
      transition (EMT) ability. Mechanistically, we observed that SBF2-AS1 served as a
      competing endogenous RNA (ceRNA) of miR-140-5p. Subsequently, transforming growth
      factor beta receptor 1 (TGFBR1) was certified as a direct target of miR-140-5p
      and enforcing SBF2-AS1 expression elevated TGFBR1 expression in HCC. Taken
      together, our study suggested that SBF2-AS1 modulated TGFBR1 through sponging miR
      140-5p in HCC development and progression indicating that SBF2-AS1 might be
      further chosen as a potential anticancer therapeutic target and a promising
      prognostic biomarker for HCC.

PMID- 30115385
TI  - Forensic epidemiology: Harnessing the power of public DNA sources to capture
      career criminals.

PMID- 30115384
TI  - Current evidence in predictors of aortic growth and events in acute type B aortic
      dissection.
AB  - OBJECTIVES: Acute type B aortic dissection can have a stable course or evolve
      into aneurysm and subsequent adverse events. The aim of this systematic review
      was to analyze the morphologic predictors of an adverse course to establish their
      validity based on consistency of results. METHODS: Fifty-one studies were
      included in this review, reporting on aortic size, false lumen (FL) size, primary
      entry tear (ET) size and location, status of FL thrombosis, number of ETs, branch
      vessels involvement, and FL longitudinal extent. RESULTS: Some predictors showed
      good consistency, whereas others did not. Aortic size was the most investigated
      predictor. A larger diameter at presentation predicted worse outcomes, with few
      exceptions. Both FL size and size relative to true lumen size also predicted an
      adverse course, although a standardized measurement method was not used.
      Regarding primary ET size and location, evidence was sparse and somewhat
      conflicting. Although FL complete thrombosis was consistently associated with a
      more benign course, the role of partial thrombosis remained unclear and the
      concept of FL saccular formation might account for the inconsistency, but further
      evidence is needed. A higher number of re-entry tears was considered to be
      protective against false channel expansion, but results need to be confirmed. The
      predictive role of branch vessels involvement and FL longitudinal extent remain
      controversial. CONCLUSIONS: Among several predictors of aortic growth and events
      in acute type B aortic dissection, controversial and even conflicting results
      have been described. Consistent evidence has been demonstrated only for two
      predictors: aortic size at presentation is associated with adverse events and
      total FL thrombosis has a protective role.

PMID- 30115387
TI  - Isolation and identification of four major impurities in capreomycin sulfate.
AB  - Capreomycin has good clinical utility to treat multidrug resistant tuberculosis,
      but it is only used as a second line drug due to its adverse reactions.
      Literature has demonstrated that the toxicity of capreomycin product is
      significantly influenced by the impurities in it. Unfortunately, so far, no one
      impurity in capreomycin has ever been isolated and definitely identified due to
      its extremely strong basic character and high polarity. An ion-pair method
      reported in literature can provide separation of capreomycin and its impurities,
      but it is hard to be used for the preparative purpose. In this study, this ion
      pair method was further improved to detect more impurities in capreomycin sulfate
      substance. Besides the four main components (IA, IB, IIA and IIB), four
      impurities (impurity A-D) with their contents much higher than the identification
      threshold were observed. Furthermore, a two dimensional (2D) LC quadrupole-time
      of flight (Q-TOF) MS method was established to realize high resolution MS
      analysis of these impurities. For the purpose of preparative isolation, a
      hydrophilic interaction chromatography (HILIC) method was established. The four
      main components were well isolated, but unfortunately, the four impurities were
      co-eluted with each other or with IB by the HILIC method. Fortunately, the
      degradation experiments revealed that IA and IB could yield clean impurity A and
      B respectively in acidic medium, and can yield clean impurity D and C
      respectively in alkaline medium. Therefore, IA and IB were first isolated by the
      preparative HILIC method, then pure IA and IB underwent acid degradation and base
      degradation separately and followed by re-isolation by the HILIC method to obtain
      pure impurity A-D respectively. Based on Q-TOF MS and NMR analysis, the
      structures (including absolute configuration) of the four isolated impurities
      were definitely identified.

PMID- 30115386
TI  - Preparation and evaluation of a reversed-phase/hydrophilic interaction/ion
      exchange mixed-mode chromatographic stationary phase functionalized with dopamine
      based dendrimers.
AB  - In this work, a novel dendritic stationary phase was synthesized by the repeated
      grafting of 1,4-butanediol diglycidyl ether (BDDE) and dopamine (DA) on the
      surface of silica for performing mixed-mode high-performance liquid
      chromatography (MHPLC). Elemental analysis (EA), thermogravimetric analysis (TGA)
      and Fourier transform infrared spectrometry (FT-IR) showed the successful
      preparation of the dendritic stationary phase. The prepared stationary phase
      showed the retention mechanisms of reversed-phase liquid chromatography (RPLC),
      hydrophilic interaction chromatography (HILIC) and ion-exchange chromatography
      (IEC) under different mobile phase conditions. In detail, alkylbenzenes,
      polycyclic aromatic hydrocarbons (PAHs) and hydrophobic positional isomers were
      separated successfully in the RPLC mode. The baseline separation of nucleobases,
      nucleosides and flavonoids was achieved under HILIC mode, respectively.
      Meanwhile, some acidic and basic analytes were used to evaluate the IEC mode. The
      effects of different chromatographic conditions, such as acetonitrile content,
      salt concentration and pH in the mobile phase, on the different chromatographic
      modes were also investigated. In addition, the application of the mixed-mode
      dendritic stationary phase was demonstrated by the analysis of traditional
      Chinese medicine (TCM), including Carthamus tinctorius L. and Abelmoschus manihot
      (Linn.) Medicus. Interestingly, the stationary phase also has the ability for the
      capture and separation of boric acids. These meaningful applications confirmed
      that the mixed-mode dendritic stationary phase can be potentially applied in the
      analysis of complex samples.

PMID- 30115388
TI  - Platelet to Lymphocyte Ratio on Admission and Prognosis in Patients with Acute
      Cardiogenic Pulmonary Edema.
AB  - BACKGROUND: Acute heart failure is a heterogenous syndrome defined by a number of
      factors, such as its physiopathology, clinical picture, time of onset, and
      relation to acute coronary syndrome. Acute cardiogenic pulmonary edema (ACPE)
      constitutes approximately 10-20% of acute heart failure syndromes, and it is the
      most dramatic symptom of left heart failure. Platelet to lymphocyte ratio (PLR)
      is a relatively novel inflammatory marker that can be utilized for prognosis in
      various disease processes. OBJECTIVE: In this study, we investigated the value of
      the PLR for the prediction of mortality in patients with ACPE. METHODS: A total
      of 115 patients hospitalized with a diagnosis of ACPE were included in this
      study. The patients were divided into tertile groups according to their PLR
      values: high (PLR > 194.97), medium (98.3-194.97), and low tertile (PLR < 98.3).
      RESULTS: We compared the PLR groups for in-hospital mortality and total mortality
      after discharge. Multivariate Cox regression analysis showed that PLR was
      independently associated with total mortality (hazard ratio 5.657; 95% confidence
      interval 2.467-12.969; p < 0.001). Survival analysis using the Kaplan-Meier curve
      showed that the high-PLR group had a significantly higher mortality rate than the
      other groups. CONCLUSIONS: We showed an association between high PLR and
      mortality in patients with ACPE. PLR, together with other inflammatory markers
      and clinical findings, may be used as an adjunctive parameter for the
      stratification of mortality risk, hospitalization, or discharge criteria scoring.

PMID- 30115389
TI  - [Search for the T790M mutation: The need to persevere].
AB  - In cases of advanced EGFR mutation-positive non-small cell lung cancer, first or
      second generation EGFR-tyrosine kinase inhibitors (TKI-EGFR 1G or TKI-EGFR 2G)
      are recommended as first line treatment. Inexorably, progressive disease occurs
      and, in 50-60% of the cases, is secondary to a T790M resistant mutation. The
      prescription of osimertinib (TKI-EGFR3G) in second line is dependent on
      identification of the T790M mutation. We report 7 cases in which the
      identification of the T790M mutation required repeated analyses of cell free DNA
      and/or biopsies over a period of time. In some cases, a positive result was
      obtained a long time after progressive disease had been diagnosed during
      treatment with first or second generation EGFR-TKI. We discuss here the different
      modalities of screening for the T790M mutation and we encourage persevering in
      this search when no alternative mechanism of resistance has been identified.

PMID- 30115390
TI  - 25-Hydroxyvitamin D Testing: Immunoassays Versus Tandem Mass Spectrometry.
AB  - Vitamin D has been associated with many health conditions. Because of widespread
      deficiency in the general population, laboratory testing of vitamin D has
      increased exponentially in recent years. Currently, 25-hydroxyvitamin D (25[OH]D)
      is considered the best marker of vitamin D status. Automated immunoassays and
      tandem mass spectrometry are the most widely used assays for the measurement of
      25(OH)D. Because a medical decision of vitamin D deficiency and treatment are
      made based on specific levels, it is important that different 25(OH)D assays are
      harmonized. Despite standardization efforts, significant differences remain among
      various methods and laboratories for the measurement of 25(OH)D.

PMID- 30115391
TI  - Pain Management Testing by Liquid Chromatography Tandem Mass Spectrometry.
AB  - For appropriate pain medication monitoring, the analytical method must be
      sensitive enough to detect the prescribed medication and metabolites at a
      sufficiently low concentration to recognize compliance, even with a low-dose
      prescription. The method must also provide excellent selectivity to identify
      simultaneously present drugs even with similar chemical structures. The
      analytical method should uncover common illicit drugs/nonprescribed medications.
      Traditional immunoassays cannot satisfy these criteria, but liquid chromatography
      tandem mass spectrometry can. It requires expensive instrumentation, careful test
      design, and extensive validation and produces a large amount of data that must be
      interpreted according to the clinical context.

PMID- 30115392
TI  - Matrix-Assisted Laser Desorption Time of Flight Mass Spectrometry.
AB  - Matrix-assisted laser desorption time of flight mass spectrometry (MALDI-TOF MS),
      adapted for use in clinical microbiology laboratories, challenges current
      standards of microbial detection and identification. This article summarizes the
      capabilities of MALDI-TOF MS in diagnostic clinical microbiology laboratories and
      describes the underpinnings of the technology, highlighting topics such as sample
      preparation, spectral analysis, and accuracy. The use of MALDI-TOF MS in the
      clinical microbiology laboratory is growing, and, when properly deployed, can
      accelerate diagnosis and improve patient care.

PMID- 30115393
TI  - Proteoform Analysis to Fulfill Unmet Clinical Needs and Reach Global
      Standardization of Protein Measurands in Clinical Chemistry Proteomics.
AB  - In clinical testing of protein markers, structure variants of the measurand are
      often not taken into account. This heterogeneous character of protein measurands
      in immunoassays often renders test standardization impossible. Consequently, test
      results from different methods can lead to underdiagnosis or overdiagnosis and,
      thus, undertreatment or overtreatment of patients. The systematic structural
      analysis of protein isoforms has been coined proteoform profiling and is
      performed through mass spectrometry-based proteomics strategies. Knowledge on
      proteoforms allows refining existing uni-marker tests and moreover has great
      potential to contribute to the urgent need for new tests to predict prognosis and
      severity of diseases.

PMID- 30115395
TI  - Accreditation and Quality Assurance for Clinical Liquid Chromatography-Mass
      Spectrometry Laboratories.
AB  - For mass spectrometry (MS) testing in the clinical laboratory, postimplementation
      monitoring for quality is just as important as method development and validation
      but often receives less attention. Quality-assurance monitoring for liquid
      chromatography-tandem MS (LC-MS/MS) testing should be proactive rather than
      reactive and should monitor the entire testing process. An LC-MS/MS quality
      assurance plan should cover overall batch review parameters, individual peak
      review parameters, system and reagent changes, and assessment of long-term
      accuracy. This article discusses Clinical Laboratory Improvement Amendments'
      regulations as they apply to LC-MS/MS-based testing and reviews available
      guidelines for LC-MS/MS quality assurance and postimplementation monitoring.

PMID- 30115394
TI  - Harmonization of Liquid Chromatography-Tandem Mass Spectrometry Protein Assays.
AB  - Harmonization of diagnostic test results is fundamental to the effective use of
      laboratory testing in the diagnosis, treatment, and monitoring of disease. Formal
      approaches to harmonization and standardization provide a rigorous and high
      quality roadmap to this end, although the formal harmonization process can be
      long and complex. In the meantime, more informal approaches to harmonization can
      provide a useful pathway to improved harmonization in the short term. Factors
      relevant to harmonization are discussed with particular attention to protein
      assays using LC-MS/MS. Published formal and informal harmonization projects are
      provided as examples, including lessons drawn from these projects.

PMID- 30115396
TI  - Liquid Chromatography-Mass Spectrometry Education for Clinical Laboratory
      Scientists.
AB  - This article describes the need for, stratifies the complexity of, and proposes
      detailed lists of training competencies for diagnostic laboratory personnel using
      quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) for
      patient care. Although quantitative LC-MS/MS is evolving toward greater
      automation with less need for technical expertise, gaps remain in resources for
      training and assessment.

PMID- 30115397
TI  - Special Considerations for Liquid Chromatography-Tandem Mass Spectrometry Method
      Development.
AB  - Method development for diagnostic liquid-chromatography-tandem mass spectrometry
      (LC-MS/MS) assays are not broadly discussed in publications. Certain aspects of
      the development process are thus learned via experience. This article touches on
      a number of aspects that should be contemplated during method development for LC
      MS/MS tests beyond sample preparation, chromatographic separation, and mass
      spectrometric detection. Utilization of factors intrinsic to LC-MS/MS, such as
      isotopically labeled internal standards and appraisal of transition ratios,
      engenders confidence in assay development and accelerates movement toward
      validation and testing.

PMID- 30115398
TI  - Development of a 25-Hydroxyvitamin D Liquid Chromatography-Tandem Mass
      Spectrometry Assay, Cleared by the Food and Drug Administration, via the De Novo
      Pathway.
AB  - Despite great improvement in vitamin D assay standardization, inaccurate
      recoveries of 25(OH)D2 remain for immunoassays and many laboratory-developed LC
      MS/MS methods don't separate out the 3-epimer interferents. Through the process
      of obtaining FDA-clearance, we learned that communication is key. Mass
      spectrometry-based assays raise different questions of safety and efficacy than
      the predicate immunoassays, with fewer risks due to increased accuracy. This
      process required improving our quality management system to support the
      development and registration of an in vitro diagnostic device. There are similar
      examples for a number of analytes, requiring expeditious entry of FDA-cleared LC
      MS/MS methods into clinical laboratories.

PMID- 30115399
TI  - It's Mass Spectrometry's Turn to Change Clinical Practice.

PMID- 30115400
TI  - ?

PMID- 30115401
TI  - Social dimension of HIV and state response.
AB  - HIV infection is strongly conditioned by social factors. Two of the most
      significant obstacles in the response to HIV is the stigma and the discrimination
      that is still associated with it. The stigmatization process occurs through
      individual drivers and structural facilitators that interweave with overlapping
      stigmas. These stig-mas manifest in several forms and lead to complex
      consequences that negatively influence prevention, diagnosis, treatment and
      quality of life. This article reviews these issues and the evidence of stigma in
      Spain. The response to HIV requires a strong political commitment. However, the
      economic crisis and the lack of leadership from institutions have slowed down the
      progress achieved in Spain. HIV must be placed at the forefront of the political
      agenda in order to achieve international goals.

PMID- 30115402
TI  - Chronicity, ageing and multimorbidity.
AB  - Thanks to highly active antiretroviral therapy (HAART), HIV-related mortality has
      been drastically reduced and HIV infection has become a chronic disease. The HIV
      infected population is ageing prematurely. Despite good immunovirological
      control, HIV causes chronic inflammation and accelerated immunosenes-cence. This
      clinically manifests as an increased prevalence of age-related comorbidity and
      frailty occurring earlier than in the general population. The heterogeneity of
      older HIV-infected adults highlights the rele-vance of identifying those who are
      at risk of poor health, and frailty may be an effective indicator. The rela
      tionship between ageing, HIV infection, antiretroviral treatment, comorbidities
      and frailty still needs to be clarified. Elderly HIV-infected adults are complex
      patients who require a specific, global and multidisci-plinary approach.

PMID- 30115403
TI  - Healthcare and economic impact.
AB  - This chapter reviews the current model of HIV patient care and its economic
      impact. There are clinical and geographical differences in the care HIV patients
      receive and a need to develop new models of comprehen-sive HIV care has been
      identified. HIV infection in Spain is an important and expensive public health
      problem. The main costs are due to an-tiretroviral therapy, indirect costs and
      the cost of admission, consultation and diagnostic testing. A strong correlation
      between severity and cost has been identified. Patients diagnosed late have a
      poorer clinical course, increased mortality and require more medical and
      therapeutic resources. Early detection of the disease significantly improves the
      clinical outcomes of patients. The increased number of patients receiving
      treatment and their progressive ageing will increase costs of HIV healthcare in
      the coming years.

PMID- 30115404
TI  - Current situation of HIV research in Spain.
AB  - Prevention, early detection, clinical follow-up, organisation and management are
      key elements in the chal-lenges to be addressed in the field of HIV infection in
      Spain. In addition to these aspects, research repre-sents a transversal element
      that is highly relevant for building up a comprehensive response against HIV
      infection. The evolution of HIV/AIDS research in Spain, major milestones and the
      development of scientific structures are analysed. An economic description of
      HIV/AIDS research funding in the context of the whole Spanish R&D system is made.
      In particular, the impact of the economic crisis and budget restrictions and
      their con-sequences on medical research are considered. Finally, different
      perspectives on the future of HIV/AIDS research in the global scientific
      situation are discussed.

PMID- 30115405
TI  - Burden of HIV infection, vulnerable populations and access barriers to
      healthcare.
AB  - In Spain, HIV incidence has remained stable and higher than the European average
      since 2000 due to insuf-ficient prevention measures. An estimated 130,000-160,000
      people are believed to be living with HIV in Spain, including 18% who do not know
      they are infected, and half are late diagnoses, with a poorer clinical course,
      lower quality of life and life expectancy, as well as higher costs. Late
      diagnosis is more common in heterosexuals, intravenous drug users, people over 50
      years of age and immigrants, whereas men who have sex with men are the only group
      where the rate of new diagnoses is increasing. An estimated 34% of people with
      HIV have a detectable viral load, mainly due to barriers that hinder diagnosis
      such as insufficient testing availability and the low risk perception of
      undiagnosed individuals and healthcare professionals.

PMID- 30115406
TI  - Primary prevention.
AB  - HIV infection is still not controlled in Spain. New HIV infection prevention
      strategies are required, especially in populations of higher incidence, by means
      of combined interventions. Early diagnosis and treatment of HIV-infected
      individuals is the most cost-effective strategy to control the epidemic,
      including interventions designed to motivate behavioural changes. These types of
      campaigns must not only be directed to the general population through mass
      channels, but also to key populations through more specific channels and
      messages. Biomedical interventions like pre-exposure prophylaxis, uses a
      combination of biomedical tools to reduce the risk of HIV acquisition, and are
      usually accompanied of behavioural interventions. The influence of structural
      factors, social justice and defending the rights of people living with HIV have a
      significant impact on prevention strategies. Structural interventions are
      designed to influence these factors that make some individuals or populations
      more vulnerable to HIV infection.

PMID- 30115407
TI  - Early diagnosis.
AB  - There is broad agreement on the impact that underdiagnosis and late diagnosis of
      HIV infection have on the health of people with HIV and on the persistence of the
      epidemic due to an inadvertent increase in transmission. The need to develop
      strategies that increase the number of diagnoses, and specifically the number of
      early diagnoses, is therefore urgent. Many such strategies have been launched in
      other countries and, in Spain, have been recommended by the Ministry of Health,
      Social Services and Equality (MSSSI). The multidisciplinary group recommends the
      review and implementation of different measures in both health and community
      settings.

PMID- 30115408
TI  - Clinical care of patients with HIV.
AB  - There has been a significant change in the clinical characteristics of people
      living with HIV, with new needs arising that must be tackled. The life expectancy
      of a subject diagnosed early with HIV infection and recei-ving suppressive
      antiretroviral therapy is currently on a par with the life expectancy of the
      general popula-tion. HIV is now a chronic treatable disease and requires a
      multidisciplinary approach that includes both the hospital medicine specialties
      and primary care physicians. The fragmented model to provide social and medical
      healthcare hinders the proper management of patients with HIV infection. There is
      significant clinical and geographical variability in the healthcare provided for
      HIV infection in Spain and the need to define and implement new models of
      healthcare delivery for this disease has been identified.

PMID- 30115409
TI  - HIV infection follow-up, organisational and management model.
AB  - Thanks to advances in antiretroviral therapy, the life expectancy of people
      infected with HIV is approaching that of the general population. In this new
      clinical scenario, comorbidities related to age and geriatric syn-dromes are
      gaining prominence. The experiences from various innovative initiatives for the
      care of patients with chronic diseases indicate that the optimisation of health
      outcomes not only depends on proper diagnosis and treatment, but also on the way
      in which care is managed. To cover the future needs of HIV-infected patients, we
      will have to implement care models that have proven effective in other types of
      chronic di-seases. This will require a reliable method to stratify patients
      according to their level of complexity or functional capacity to detect the most
      vulnerable cases.

PMID- 30115410
TI  - Boldine-loaded PLGA nanoparticles have improved efficiency of drug carriage and
      protective potential against Cisplatin-induced toxicity.
AB  - BACKGROUND: Cisplatin is a widely-used potent anti-cancer drug having severe side
      effects precluding its sustained use. OBJECTIVES: Poly (lactide-co-glycolide)
      (PLGA)-nanoparticles loaded Boldine, an antioxidant ingredient of ethanolic
      extract of Boldo plant (Peumus boldus) was tested in cancer mice model, Mus
      musculus to examine if it could reduce unwanted Cisplatin-induced toxicity in
      normal tissue. MATERIAL AND METHODS: Nano-encapsulation of Boldine was done by
      following the standardized solvent displacement method. Physico-chemical
      characterization of PLGA-encapsulated nano-Boldine (NBol) was accomplished
      through analyses of various spectroscopic techniques. Status of major antioxidant
      enzymes, functional markers, and lipid peroxidation (LPO) was also determined in
      certain tissue and serum samples. Percentage of cells undergoing cytotoxic death,
      Reactive oxygen species (ROS) accumulation and mitochondrial functioning were
      analyzed in both normal and cancer mice. Nanoscale changes in chromatin
      organization were assessed by Transmission electron microscopy (TEM). mRNA and
      protein expressions of Top II, Bax, Bcl-2, Cyt c, caspase 3 were studied by RT
      PCR, immunoblot and immunofluorescence. RESULTS: NBol had faster mobility, site
      specific action and ability of sustained particle release. NBol readily entered
      cells, prevented Cisplatin to intercalate with dsDNA resulting in reduction of
      chromatin condensation, with corresponding changes in ROS levels, mitochondrial
      functioning and antioxidant enzyme activities, leading to reduction in
      Deoxyribose nucleic acid (DNA) damage and cytotoxic cell death. Expression
      pattern of apoptotic genes like Top II, p53, Bax, Bcl-2, cytochrome c and caspase
      3 suggested greater cytoprotective potentials of NBol in normal tissues.
      CONCLUSIONS: Compared to Boldine (Bol), NBol had better ability of drug carriage
      and protective potentials (29.00% approximately) against Cisplatin-induced
      toxicity. Combinational therapeutic use of PLGA-NBol can reduce unwanted
      Cisplatin-induced cellular toxicity facilitating use of Cisplatin.

PMID- 30115411
TI  - Consumer credit scores as a novel tool for identifying health in urban U.S.
      neighborhoods.
AB  - PURPOSE: Credit scores may operate as a socioeconomic indicator of health: they
      represent cumulative financial history that directly influences ability to access
      financial and nonfinancial resources related to health. Yet, little is known
      about the relationship of credit score and health or to traditional measures of
      socioeconomic position (SEP). Our objectives were to (1) evaluate the association
      between area-level credit score and individual self-rated health and (2) compare
      credit score to traditional markers of area-level SEP in predicting self-rated
      health. METHODS: Equifax estimates of average household credit score in 2015
      among nine-digit zip code regions were combined with a representative survey of
      2083 residents of Philadelphia to estimate the correlation with income, housing
      value, education, and occupational status and then predict the odds of self-rated
      health for credit score and each SEP measure. RESULTS: Credit score was
      moderately correlated with SEP markers (r = -0.78 to 0.49). After adjusting for
      area- and individual-level SEP and demographic factors, each SD increase in
      credit score is associated with 26% greater odds of better self-rated health
      (odds ratio = 1.26, 95% confidence interval: 1.09-1.46). Credit score had a
      larger effect size than other SEP markers. CONCLUSIONS: Credit score may be a
      useful complement to traditional measures of SEP in assessing health outcomes.

PMID- 30115413
TI  - The Lombard Effect: From Acoustics to Neural Mechanisms.
AB  - Understanding the neural underpinnings of vocal-motor control in humans and other
      animals remains a major challenge in neurobiology. The Lombard effect - a rise in
      call amplitude in response to background noise - has been demonstrated in a wide
      range of vertebrates. Here, we review both behavioral and neurophysiological data
      and propose that the Lombard effect is driven by a subcortical neural network,
      which can be modulated by cortical processes. The proposed framework offers
      mechanistic explanations for two fundamental features of the Lombard effect: its
      widespread taxonomic distribution across the vertebrate phylogenetic tree and the
      widely observed variations in compensation magnitude. We highlight the Lombard
      effect as a model behavioral paradigm for unraveling some of the neural
      underpinnings of audiovocal integration.

PMID- 30115414
TI  - Patient perceptions of participation in group-based rehabilitation in an
      inpatient brain injury rehabilitation setting.
AB  - OBJECTIVES: The use of groups is common in healthcare. There is a paucity of
      research which captures patient experiences of group participation. The aims of
      this study were to explore the perceptions and experiences of people with
      traumatic brain injury (TBI) about their participation in inpatient occupational
      therapy rehabilitation groups. METHOD: A phenomenological approach guided the
      study. Patients with a TBI who were participating in an inpatient occupational
      therapy group program were recruited. Data were collected through semi-structured
      interviews and analysed using content analysis. RESULTS: Fifteen participants
      consented to the study. Three themes emerged from the data; 1) feeling normal,
      comfortable and connected; 2) learning by doing, seeing and sharing and; 3)
      practicalities of groups. Participants highlighted that groups facilitated
      opportunities to practice skills and prepared them for the real world.
      Opportunities for interaction and support were also emphasised as positive by
      participants. CONCLUSION: Perceptions of patients about participation in groups
      were generally positive, and as such a consumer-focused approach to healthcare
      would support the use of occupational therapy groups in TBI rehabilitation.
      PRACTICE IMPLICATIONS: Recommendations from the perspectives of patients include
      consideration of the selection of group participants, and meeting individual
      needs and goals within a group setting.

PMID- 30115412
TI  - The Posterior Parietal Cortex in Adaptive Visual Processing.
AB  - Although the primate posterior parietal cortex (PPC) has been largely associated
      with space, attention, and action-related processing, a growing number of studies
      have reported the direct representation of a diverse array of action-independent
      nonspatial visual information in the PPC during both perception and visual
      working memory. By describing the distinctions and the close interactions of
      visual representation with space, attention, and action-related processing in the
      PPC, here I propose that we may understand these diverse PPC functions together
      through the unique contribution of the PPC to adaptive visual processing and form
      a more integrated and structured view of the role of the PPC in vision,
      cognition, and action.

PMID- 30115415
TI  - Accuracy and congruence of physician and adolescent patient weight-related
      discussions: Teen CHAT (Communicating health: Analyzing talk).
AB  - OBJECTIVE: We assessed the accuracy and congruence of recall of weight topics
      during clinical encounters between adolescent patients with overweight/obesity
      and physicians (randomized to Motivational Interviewing education vs. control
      arm). METHODS: We audio recorded 357 clinic encounters and coded topics of
      weight, physical activity (PA), breakfast, and fast food. We assessed recall
      accuracy/congruence. Generalized estimation equation modeling assessed
      associations between selected factors and recall accuracy. RESULTS: Accuracy for
      physicians was: weight (90%), PA (88%), breakfast (77%) and fast food (70%).
      Patient accuracy was: weight (94%), PA (94%), breakfast (73%) and fast food
      (61%). Physician/patient congruence was: weight (89%), PA (90%), breakfast (71%)
      and fast food (67%). Use of a reminder report indicating adolescent's weight
      behaviors in the physician control group resulted in increased adolescent (p =
      0.02) and physician accuracy (p = 0.05) for fast food. Adolescents were more
      likely to recall discussions of fast food (odds ratio, 0.87; 95% CI, 0.77-0.97)
      as encounter time decreased; male adolescents were less likely to recall
      breakfast than females (odds ratio, 0.52; 95% CI, 0.28-0.95). CONCLUSION:
      Adolescents and physicians recall weight and PA more often, perhaps indicating
      greater engagement in these topics. PRACTICE IMPLICATIONS: Reminder reports might
      possibly enhance discussion and recall of diet related messages.

PMID- 30115416
TI  - Socioeconomic disadvantages in childhood and metabolic syndrome risk: A call to
      action?

PMID- 30115417
TI  - Advanced interatrial block predicts atrial fibrillation recurrence across
      different populations: Learning Bayes syndrome.

PMID- 30115418
TI  - Plasminogen activator inhibitor-1 and tissue plasminogen activator and incident
      AF: Data from the PREVEND study.

PMID- 30115420
TI  - Cardiovascular risk assessment tools in non-Western populations.

PMID- 30115419
TI  - Dual versus triple therapy in patients on oral anticoagulants and undergoing
      coronary stent implantation: A systematic review and meta-analysis.
AB  - BACKGROUND AND AIMS: There is contrasting evidence regarding the optimal
      antithrombotic regimen after percutaneous coronary stent implantation in patients
      on oral anticoagulants. A systematic review and meta-analysis was performed to
      explore the comparative efficacy and safety of dual (an antiplatelet plus an oral
      anticoagulant) versus triple therapy (dual antiplatelet therapy plus an oral
      anticoagulant). METHODS: We searched the literature for randomized controlled
      trials (RCTs) or observational studies (OSs) addressing this issue. The efficacy
      outcomes were all-cause mortality, cardiovascular mortality, myocardial
      infarction and stent thrombosis. The safety outcomes were major bleeding events
      and all bleeding events. The analyses were stratified by type of anticoagulant
      and of antiplatelet used in dual therapy. RESULTS: Four RCTs and ten OSs met our
      inclusion criteria including a total of 10,126 patients. 5671 patients received
      triple therapy whereas 4455 received dual therapy. Median follow up was 12
      months. There was no difference between dual therapy and triple therapy regarding
      efficacy outcomes. Dual therapy significantly reduced the risk of major bleeding
      (RR 0.66; CI 95% 0.52-0.83; P = 0.0005) and of all bleeding events (RR 0.67, CI
      95% 0.55-0.80; P < 0.0001). The effect was consistent regardless of the type of
      antiplatelet and anticoagulant used in dual therapy. CONCLUSION: Dual
      antithrombotic therapy after coronary stenting in anticoagulated patients
      significantly reduces bleeding events compared with triple therapy. Dual therapy
      might be considered in this setting especially when bleeding risk outweighs
      ischemic risk, although our study was not sufficiently powered to detect a
      difference in ischemic endpoints.

PMID- 30115421
TI  - Defining the Role of Point-of-Care Ultrasound in Cardiovascular Disease.
AB  - Echocardiography is the foundation for diagnostic cardiac testing, allowing for
      direct identification and management of various conditions. Point-of-care
      ultrasound (POCUS) has emerged as an invaluable tool for bedside diagnosis and
      management. The objective of this review is to address the current use and
      clinical applicability of POCUS to identify, triage, and manage a wide spectrum
      of cardiac conditions. POCUS can change diagnosis and management decisions of
      various cardiovascular conditions in a range of settings. In the outpatient
      setting, it is used to risk stratify and diagnose a variety of medical
      conditions. In the emergency department (ED) and critical care settings, it is
      used to guide triage and critical care interventions. Furthermore, the skills
      needed to perform POCUS can be taught to noncardiologists in a way that is
      retained and allows identification of normal and grossly abnormal cardiac
      findings. Various curricula have been developed that teach residents and advanced
      learners how to appropriately employ point-of-care ultrasound. In conclusion,
      POCUS can be a useful adjunct to the physical exam, particularly in critical care
      applications.

PMID- 30115423
TI  - Comparison of Complications of Catheter Ablation for Ventricular Arrhythmias in
      Adults With Versus Without Structural Heart Disease.
AB  - Catheter ablation (CA) is an effective treatment for ventricular arrhythmias
      (VA), with a potential for complications. The presence of structural heart
      disease (SHD) is associated with a higher complication rate although there is no
      data comparing CA of VA between patients with SHD and those without. We aimed to
      compare trends, morbidity, and mortality associated with real world practice of
      CA for VA (ventricular tachycardia and premature ventricular contraction) based
      on the presence of SHD. Using weighted sampling in the National Inpatient Sample
      database, we collected and compared characteristics and outcomes of patients with
      or without SHD that underwent CA of VA. Among 34,907 patients that underwent CA
      for VA (1999-2013), 18,014 (51.6%) had SHD. Major and all complications occurred
      among 1,135/18,014 (6.3%) and 2139/18,014 (11.9%) patients with SHD respectively
      compared with 355/16,893 (2.1%) and 739/16,893 (4.4%) for patients without SHD, p
      < 0.001 for both comparisons. Furthermore, 452/18,014 (2.51%) with SHD died
      versus 20/16,893 (0.12%) without SHD, p < 0.001. Heart failure was associated
      with an odds ratio (OR) of 3.09 for major complications (95%CI: 1.53-6.27, p =
      0.002) for patients with SHD while coronary artery disease OR for major
      complications was 2.47 (95%CI: 1.44-4.23, p = 0.001) for patients without SHD.
      There was a significant increase in major complications over the 15-year study
      period in patients with SHD, p < 0.001. In conclusion, the presence of SHD during
      CA for VA increased the complication rate of major and any complications by
      approximately threefold for both and the hospital mortality by >20-fold compared
      with patients without SHD.

PMID- 30115422
TI  - Bleeding Events After ST-segment Elevation Myocardial Infarction in Patients
      Randomized to an All-comer Clinical Trial Compared With Unselected Patients.
AB  - Most studies reporting bleedings in patients with ST-segment elevation myocardial
      infarction (STEMI) are reports from clinical trials, which may be
      unrepresentative of incidences in real-life. In this study, we investigated 1
      year bleeding and mortality incidences in an unselected STEMI population, and
      compared participants with nonparticipants of a randomized all-comer clinical
      trial (The Third DANish Study of Optimal Acute Treatment of Patients with STEMI
      (DANAMI-3)). Hospital charts were read and bleedings classified according to
      thrombolysis in myocardial infarction (TIMI) and Bleeding Academic Research
      Consortium (BARC) criteria in 2,490 consecutive STEMI patients who underwent
      primary percutaneous coronary intervention in a single, large, and tertiary heart
      center. Thrombolysis in myocardial infarction minor and/or major bleeding (TMMB)
      occurred in 4.4% day 0 to 30 and 2.1% day 31 to 365. DANAMI-3 nonparticipants (n
      = 887) had significantly higher 30-day bleeding rates than DANAMI-3-participants
      (n = 1,603) (7.2% vs 2.9%, p <0.0001), but not thereafter (p = 0.8). DANAMI-3
      nonparticipation was significantly associated with 30-day TMMB (hazard ratio,
      1.8, 95% confidence interval, 1.2 to 2.8, p = 0.007), but this did not persist
      after adjusting for resuscitated cardiac arrest, Killip-class>2 and anemia.
      Patients with cardiac arrest, Killip-class>2, and anemia accounted for 70.0% of
      30-day TMMBs, and the majority of these patients were DANAMI-3 nonparticipants.
      TMMB day 0 to 30 was associated with increased 30-day mortality (hazard ratio
      3.1, 95% confidence interval 1.9 to 5.2, p <0.0001) but not thereafter (p = 0.9).
      In conclusion, we found that clinical trial (DANAMI-3) nonparticipants had
      significantly more TMMBs within 30 days than participants. Patients with
      resuscitated cardiac arrest, anemia, and Killip-class>2 were accountable for a
      high rate of TMMBs. Bleeding incidences from clinical trials cannot be translated
      to an unselected STEMI population.

PMID- 30115424
TI  - Frequency of Ventricular Arrhythmias and Other Rhythm Abnormalities in Children
      and Young Adults With the Marfan Syndrome.
AB  - Patients with the Marfan syndrome (MFS) are at risk for sudden death. The
      contribution of arrhythmias is unclear. This study examines the prevalence of
      arrhythmias in children with the MFS and their relation to clinical and/or
      echocardiographic factors. Data from the Pediatric Heart Network randomized trial
      of atenolol versus losartan in MFS were analyzed (6 months to 25 years old,
      aortic root diameter z-score > 3.0, no previous aortic surgery and/or
      dissection). Baseline 24-hour ambulatory electrocardiographic monitoring was
      performed. Significant ventricular ectopy (VE) and supraventricular ectopy (SVE)
      were defined as >=10 VE or SVE/hour, or the presence of high-grade ectopy. Three
      year composite clinical outcome of death, aortic dissection, or aortic root
      replacement was analyzed. There were 274 analyzable monitors on unique patients
      from 11 centers. Twenty subjects (7%) had significant VE, 13 (5%) significant
      SVE; of these, 2 (1%) had both. None had sustained ventricular or
      supraventricular tachycardia. VE was independently associated with increasing
      number of major Ghent criteria (odds ratio [OR] = 2.13/each additional criterion,
      p = 0.03) and greater left ventricular end-diastolic dimension z-score (OR =
      1.47/each 1 unit increase in z-score, p = 0.01). SVE was independently associated
      with greater aortic sinotubular junction diameter z-score (OR = 1.56/each 1 unit
      increase in z-score, p = 0.03). The composite clinical outcome (14 events) was
      not related to VE or SVE (p >= 0.3), but was independently related to heart rate
      variability (higher triangular index). In conclusion, in this cohort, VE and SVE
      were rare. VE was related to larger BSA-adjusted left ventricular size. Routine
      ambulatory electrocardiographic monitoring may be useful for risk stratification
      in select MFS patients.

PMID- 30115425
TI  - Comparison of Frequency of Atherosclerotic Cardiovascular and Safety Events With
      Systolic Blood Pressure <120mm Hg Versus 135-139mm Hg in a Systolic Blood
      Pressure Intervention Trial Primary Prevention Subgroup.
AB  - Whether the benefit of intensive blood pressure (BP) control reduces
      atherosclerotic cardiovascular disease (ASCVD) risk without increasing risks of
      serious adverse events (SAEs) is unknown. We sought to assess differences in
      incident ASCVD and SAE with intensive BP control across the spectrum of 10-year
      ASCVD risk in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT
      randomized 9,361 participants who were >=50years old and >=1 CVD risk factor to
      standard or intensive BP control (<120 or 130 to 139mm Hg). We excluded adults
      with clinical ASCVD or age >=80. We included 6,875 participants. We compared
      hazard ratios (HR) and risk differences (RD) of incident ASCVD events or SAEs in
      all and across quartiles of baseline risk. Median predicted ASCVD risk was 15.9%.
      Intensive BP control significantly reduced ASCVD events (HR 0.75, 95% confidence
      interval 0.58, 0.97, p = 0.03; RD -0.94; -1.8, -0.1; p = 0.03). There was no
      difference in effect across quartiles of ASCVD risk. There was a non-significant
      increase in SAE with intensive BP control (HR 1.08, 1.00, 1.17 p = 0.06; RD 2.1, 
      0.1, 4.4, p = 0.03), and no difference in this effect across quartiles of risk.
      In SPRINT participants without baseline clinical ASCVD, the benefit of intensive
      BP control for primary prevention of ASCVD may extend to lower risk participants
      without an increase in SAE. In conclusion, lower risk adults with stage 1
      hypertension meeting SPRINT eligibility may benefit from initiation of
      antihypertensives.

PMID- 30115426
TI  - Previous and New Onset Atrial Fibrillation and Associated Outcomes in Acute
      Coronary Syndromes (from the Global Registry of Acute Coronary Events).
AB  - Atrial fibrillation (AF) is a frequent complication of acute coronary syndromes
      (ACS) and is associated with an increased risk of in-hospital and long-term
      mortality. Our objective was to determine whether patients with previous AF and
      those who presented with or developed AF during their ACS hospitalization (new
      onset) have an associated increased risk of short- and mid-term cardiovascular
      events, death, or a composite. We included 7,228 patients from the Global
      Registry of Acute Coronary Events electrocardiogram core laboratory substudy, who
      presented with an ACS. Associated multivariable-adjusted risk of death and major
      adverse cardiovascular events (MACE) of death, re-infarction, or stroke in
      hospital and at 6 months were estimated. New-onset AF and previous AF patients
      had higher rates of in-hospital mortality (14.9% and 10.9%, respectively)
      compared with patients without AF (3.8%; both p < 0.001). New-onset AF and
      previous AF patients had higher rates of 6-month mortality (22.3% and 21.3%,
      respectively) compared with patients without AF (7.0%; both p <0.001). After
      adjustment for clinical prognosticators, including those in the Global Registry
      of Acute Coronary Events risk model, new-onset AF was associated with higher
      mortality in-hospital (ORadj 1.87, 95% CI 1.30 to 2.70) and at 6 months (ORadj
      1.75, 95% CI 1.29 to 2.39) as well as MACE at 6 months (ORadj 1.43, 95% CI 1.12
      to 1.81) compared with patients without AF, but were at similar risk compared to
      those with previous AF (all p > 0.40). In conclusion, the risk of death and MACE
      after ACS in patients with new-onset and previous AF appears similar and
      significantly increased compared with patients without AF.

PMID- 30115427
TI  - Multiclonal tumor origin: Evidence and implications.
AB  - An accurate understanding of the clonal origins of tumors is critical for
      designing effective strategies to treat or prevent cancer and for guiding the
      field of cancer risk assessment. The intent of this review is to summarize
      evidence of multiclonal tumor origin and, thereby, contest the commonly held
      assumption of monoclonal tumor origin. This review describes relevant studies of
      X chromosome inactivation, analyses of tumor heterogeneity using other markers,
      single cell sequencing, and lineage tracing studies in aggregation chimeras and
      engineered rodent models. Methods for investigating tumor clonality have an
      inherent bias against detecting multiclonality. Despite this, multiclonality has
      been observed within all tumor stages and within 53 different types of tumors.
      For myeloid tumors, monoclonal tumor origin may be the predominant path to cancer
      and a monoclonal tumor origin cannot be ruled out for a fraction of other cancer
      types. Nevertheless, a large body of evidence supports the conclusion that most
      cancers are multiclonal in origin. Cooperation between different cell types and
      between clones of cells carrying different genetic and/or epigenetic lesions is
      discussed, along with how polyclonal tumor origin can be integrated with current
      perspectives on the genesis of tumors. In order to develop biologically sound and
      useful approaches to cancer risk assessment and precision medicine, mathematical
      models of carcinogenesis are needed, which incorporate multiclonal tumor origin
      and the contributions of spontaneous mutations in conjunction with the selective
      advantages conferred by particular mutations and combinations of mutations.
      Adherence to the idea that a growth must develop from a single progenitor cell to
      be considered neoplastic has outlived its usefulness. Moving forward, explicit
      examination of tumor clonality, using advanced tools, like lineage tracing
      models, will provide a strong foundation for future advances in clinical oncology
      and better training for the next generation of oncologists and pathologists.

PMID- 30115428
TI  - DNA methylation signatures: Biomarkers of drug and alcohol abuse.
AB  - DNA sequence is a powerful tool that can be used for an individual's
      identification and investigation of various abnormalities in the genome. However,
      recent studies have identified other heritable changes by epigenetic mechanisms
      that cause changes in gene expression without altering the DNA sequence itself.
      In particular, DNA methylation mediates long-lasting changes in gene promoters,
      which makes it an appealing epigenetic mechanism to study variation in
      methylation status that characterizes the extent of drug abuse. We summarize
      recent findings on methylation alterations in a number of genes caused by various
      drugs including cocaine, opioids, cannabinoids, amphetamine, phenobarbital, and
      alcohol in various human and animal model studies. Additionally, a minimal
      discussion of the basic concepts of methylation is provided. The determination of
      possible DNA methylation alterations can assist in finding the cause and
      circumstances of death or ailment, and gene markers can be potentially used as
      biomarkers in the future.

PMID- 30115430
TI  - Rare anemias due to genetic iron metabolism defects.
AB  - Anemia is defined by a deficiency of hemoglobin, an iron-rich protein that binds
      oxygen in the blood. It can be due to multiple causes, either acquired or
      genetic. Alterations of genes involved in iron metabolism may be responsible,
      usually at a young age, for rare forms of chronic and often severe congenital
      anemia. These diseases encompass a variety of sideroblastic anemias,
      characterized by the presence of ring sideroblasts in the bone marrow. Clinical
      expression of congenital sideroblastic anemia is either monosyndromic (restricted
      to hematological lineages) or polysyndromic (with systemic expression), depending
      on whether iron metabolism, and especially heme synthesis, is directly or
      indirectly affected. Beside sideroblastic anemias, a number of other anemias can
      develop due to mutations of key proteins acting either on cellular iron transport
      (such as the DMT1 transporter), plasma iron transport (transferrin), and iron
      recycling (ceruloplasmin). Contrasting with the aforementioned entities which
      involve compartmental, and sometimes, systemic iron excess, the iron refractory
      iron deficiency anemia (IRIDA) corresponds to a usually severe anemia with whole
      body iron deficiency related to chronic increase of plasma hepcidin, the systemic
      negative regulator of plasma iron. Once clinically suggested, these diseases are
      confirmed by genetic testing in specialized laboratories.

PMID- 30115429
TI  - Mutational game changer: Chromothripsis and its emerging relevance to cancer.
AB  - In recent years, the paradigm that genomic abnormalities in cancer cells arise
      through progressive accumulation of mutational events has been challenged by the
      discovery of single catastrophic events. One such phenomenon termed
      chromothripsis, involving massive chromosomal rearrangements arising all at once,
      has emerged as a major mutational game changer. The strong interest in this
      process stems from its widespread association with a range of cancer types and
      its potential as a mutational driver. In this review, we first describe
      chromothripsis detection and incidence in cancers. We then explore recently
      proposed underlying mechanistic origins, which explain the curious observations
      of the highly localised nature of the rearrangements on chromothriptic
      chromosomes. Detection of chromothriptic patterns following incorporation of
      single chromosomes into micronuclei or following telomere attrition have greatly
      contributed to our understanding of the reasons behind this chromosomal
      restriction. These underlying cellular events have been found to be participants
      in the tumourigenic process, strongly suggesting a potential role for
      chromothripsis in cancer development. Thus, we discuss potential implications of
      chromothripsis for cancer progression and therapy.

PMID- 30115432
TI  - Ten Questions About Barium Esophagography and Dysphagia.
AB  - The barium esophagogram is a global test for patients with dysphagia that can
      simultaneously detect morphologic abnormalities in the pharynx and esophagus,
      pharyngeal swallowing dysfunction, esophageal dysmotility, and gastroesophageal
      reflux. The barium esophagram is an inexpensive, noninvasive, and widely
      available procedure that can serve as the initial diagnostic test for dysphagia
      and facilitate selection of other diagnostic studies such as endoscopy. This
      article addresses 10 questions about barium esophagography and dysphagia that
      should help gastroenterologists gain a better perspective about the utility of
      barium studies in this clinical setting.

PMID- 30115433
TI  - Computed Tomography and Magnetic Resonance Small Bowel Enterography: Current
      Status and Future Trends Focusing on Crohn's Disease.
AB  - Computed tomography enterography (CTE) and magnetic resonance enterography (MRE)
      are presently state-of-the-art radiologic tests used to examine the small bowel
      for various indications. This article focuses on CTE and MRE for the evaluation
      of Crohn disease. The article describes recent efforts to achieve more
      standardized interpretation of CTE and MRE, summarizes recent research studies
      investigating the role and impact of CTE and MRE more directly for several
      different clinical and research issues beyond general diagnostic accuracy, and
      provides an update on progress in imaging techniques. Also addressed are areas
      that need further exploration in the future.

PMID- 30115431
TI  - Impact of obesity and overweight on DNA stability: Few facts and many hypotheses.
AB  - Health authorities are alarmed worldwide about the increase of obesity and
      overweight in the last decades which lead to adverse health effects including
      inflammation, cancer, accelerated aging and infertility. We evaluated the state
      of knowledge concerning the impact of elevated body mass on genomic instability.
      Results of investigations with humans (39 studies) in which DNA damage was
      monitored in lymphocytes and sperm cells, are conflicting and probably as a
      consequence of heterogeneous study designs and confounding factors (e.g.
      uncontrolled intake of vitamins and minerals and consumption of different food
      types). Results of animal studies with defined diets (23 studies) are more
      consistent and show that excess body fat causes DNA damage in multiple organs
      including brain, liver, colon and testes. Different molecular mechanisms may
      cause genetic instability in overweight/obese individuals. ROS formation and
      lipid peroxidation were found in several investigations and may be caused by
      increased insulin, fatty acid and glucose levels or indirectly via inflammation.
      Also reduced DNA repair and formation of advanced glycation end products may play
      a role but more data are required to draw firm conclusions. Reduction of telomere
      lengths and hormonal imbalances are characteristic for overweight/obesity but the
      former effects are delayed and moderate and hormonal effects were not
      investigated in regard to genomic instability in obese individuals. Increased BMI
      values affect also the activities of drug metabolizing enzymes which
      activate/detoxify genotoxic carcinogens, but no studies concerning the impact of
      these alterations of DNA damage in obese individuals are available. Overall, the
      knowledge concerning the impact of increased body weight and DNA damage is poor
      and further research is warranted to shed light on this important issue.

PMID- 30115434
TI  - Radiologic Assessment of Gastrointestinal Bleeding.
AB  - Gastrointestinal (GI) bleeding represents a broad differential of disease
      throughout the GI tract. The proper diagnostic evaluation of patients presenting
      with symptoms of GI bleeding depends on the overall clinical acuity and suspected
      source locations. The radiologic assessment of these patients is centered around
      computed tomography (CT) angiography, CT enterography, conventional angiography,
      and nuclear scintigraphy.

PMID- 30115437
TI  - Defecography: An Overview of Technique, Interpretation, and Impact on Patient
      Care.
AB  - Pelvic floor and defecatory dysfunction are common in the female patient
      population. When combined with physical examination, barium defecography allows
      for accurate and expanded assessment of the underlying pathology and helps to
      guide future intervention. Understanding the imaging findings of barium
      defecography in the spectrum of pathology of the anorectum and pelvic floor
      allows one to appropriately triage and treat patients presenting with defecatory
      dysfunction.

PMID- 30115436
TI  - Rectal MRI for Cancer Staging and Surveillance.
AB  - MRI is an integral part of the multidisciplinary treatment of rectal
      adenocarcinoma. Staging MRI is performed to establish TNM stage and assess for
      prognostic factors, including circumferential resection margin status and
      presence of extramural vascular invasion. The results of staging MRI determine
      which patients will undergo preoperative neoadjuvant chemoradiation before
      resection. Restaging MRI is performed to evaluate for treatment response and may
      identify patients with no residual visible tumor who are candidates for a "watch
      and wait" strategy in lieu of resection. In addition, the results of MRI in
      conjunction with endoscopy determine the surgical technique used to remove the
      tumor.

PMID- 30115438
TI  - Multidetector Computed Tomography for Retrospective, Noninvasive Staging of Liver
      Fibrosis.
AB  - Although not traditionally used to assess hepatic fibrosis, computed tomography
      (CT) is fast, accessible, robust, and commonly used for abdominal indications. CT
      metrics are often easily retrospectively obtained without special equipment.
      Metrics such as liver segmental volume ratio, which quantifies regional hepatic
      volume changes; splenic volume; and liver surface nodularity scoring show
      diagnostic performance comparable to elastography techniques for detecting
      significant and advanced fibrosis. Other emerging CT tools, such as CT texture
      analysis and fractional extracellular volume, have also shown promise in
      identifying fibrosis and warrant further study.

PMID- 30115439
TI  - Role of Imaging in Surveillance and Diagnosis of Hepatocellular Carcinoma.
AB  - The prognosis for hepatocellular carcinoma (HCC) is dependent on tumor stage at
      diagnosis, with curative treatment options more available to early-detected HCCs.
      Professional organizations have produced HCC screening guidelines in at-risk
      groups, with ultrasound the most commonly used screening tool and increased
      interest in MRI in specific populations. HCC may be diagnosed by imaging features
      alone and have been universally incorporated into management guidelines. The
      radiology community has standardized imaging criteria for HCC with the
      development of the Liver Imaging Reporting and Data System, which has expanded to
      incorporate computed tomography, MR, and contrast-enhanced ultrasound for
      diagnostic purposes.

PMID- 30115435
TI  - The Natural History of Colorectal Polyps: Overview of Predictive Static and
      Dynamic Features.
AB  - For decades, colorectal screening strategies have been largely driven by static
      features, particularly polyp size. Although cross-sectional features of polyp
      size, morphology, and location are important determinants of clinical relevance
      before histology, they lack any dynamic information on polyp growth rates.
      Computed tomography colonography allows for in vivo surveillance of colorectal
      polyps, providing volumetric growth rates that are providing new insights into
      tumorigenesis. In this article, existing cross-sectional and longitudinal data on
      colorectal polyps are reviewed, with an emphasis on how these features may affect
      clinical relevance and patient management.

PMID- 30115440
TI  - Imaging in Autoimmune Pancreatitis and Immunoglobulin G4-Related Disease of the
      Abdomen.
AB  - Autoimmune pancreatitis (AIP) is steroid-responsive fibroinflammatory disorder of
      the pancreas. There are 2 distinct subtypes of AIP, types 1 and 2. Type 1 is
      associated with systemic immunoglobulin (Ig)G4 disease and may affect multiple
      organs in the body. Type 2 is confined to the pancreas and shows an association
      with ulcerative colitis. This article describes the imaging findings of AIP and
      IgG4 disease in the liver, bile ducts, kidneys, and the retroperitoneal regions.
      The imaging differentiation of AIP from pancreas cancer is discussed.

PMID- 30115441
TI  - Percutaneous Biliary Interventions.
AB  - Biliary drainage is important in the care of patients with benign and malignant
      biliary obstruction. Careful preprocedure evaluation of high-quality cross
      sectional imaging and inventory of symptoms are necessary to determine whether a
      percutaneous, endoscopic, or surgical approach is most appropriate. High bile
      duct obstruction is usually best managed percutaneously; a specific duct can be
      targeted and enteric contamination of isolated ducts can be avoided. Options for
      percutaneous biliary intervention include external or internal/external biliary
      drainage, stent placement, biliary stone retrieval, and bile duct biopsy.
      Preprocedure evaluation, technique, and indications for percutaneous intervention
      in benign and malignant diseases are summarized.

PMID- 30115442
TI  - Splenomegaly: A Combined Clinical and Radiologic Approach to the Differential
      Diagnosis.
AB  - An enlarged spleen (splenomegaly) is a common imaging finding and may be related
      to a broad array of underlying conditions. The multifaceted functions of the
      spleen make it susceptible to involvement by a variety of pathophysiologic
      processes. Understanding these conditions and incorporating all relevant clinical
      and radiologic data allow narrowing the differential diagnosis.

PMID- 30115444
TI  - PET/MRI for Gastrointestinal Imaging: Current Clinical Status and Future
      Prospects.
AB  - Positron emission tomography (PET)/computed tomography (CT) with 2-deoxy-2
      [18F]fluoro-d-glucose (FDG) has become the standard of care for the initial
      staging and subsequent treatment response assessment for numerous
      gastrointestinal malignancies. However, it is often supplemented by magnetic
      resonance imaging (MRI) for local tumor staging. Hybrid PET/MRI scanners, which
      acquire PET data and MRI data simultaneously, have the potential to provide
      accurate whole-body staging in a single examination. Furthermore, to address
      certain limitations of FDG, many new PET tracers have been developed to probe
      distinctive aspects of tumor biology.

PMID- 30115443
TI  - MRI of the Nontraumatic Acute Abdomen: Description of Findings and Multimodality
      Correlation.
AB  - Obtaining a specific diagnosis in the nontraumatic acute abdomen can be
      clinically challenging, because a wide range of disease processes affecting a
      number of different organ systems may have very similar presentations. Although
      computed tomography and ultrasound examination are the imaging tests most
      commonly used to evaluate the acute abdomen, MRI can often offer comparable
      diagnostic performance, and may be considered when other modalities are
      equivocal, suboptimal, or contraindicated. In some circumstances, MRI is emerging
      as an appropriate first-line imaging test.

PMID- 30115445
TI  - Diagnostic Imaging: A Peephole into Many of the Body's Dressing Rooms.

PMID- 30115446
TI  - Gastrointestinal Imaging: Rapid Advancements Leading to Improved Patient Care.

PMID- 30115447
TI  - Intraoperative tap test for coronal syndesmotic instability: A cadaveric study.
AB  - INTRODUCTION: Precise diagnosis of distal tibiofibular syndesmotic injury is
      challenging, and a gold standard diagnostic test has still not been established.
      Tibiofibular clear space identified on radiographic imaging is considered the
      most reliable indicator of the injury. The Cotton test is the most widely used
      intraoperative technique to evaluate the syndesmotic integrity although it has
      its limitations. We advocate for a novel intra operative test using a 3.5 mm
      blunt cortical tap. METHODS: Tibiofibular clear space was assessed in nine
      cadaveric specimens using three sequential fluoroscopic images. The first image
      was taken prior to the application of the tap test (intact, non-stressed). Then,
      a 2.5 mm hole was drilled distally on the lateral fibula, and a 3.5 mm cortical
      tap was then threaded in the hole. The tap test involved gradually advancing the
      blunt tip against the lateral tibia, providing a tibiofibular separation force
      (intact, stressed). This same stress was then applied after all syndesmotic
      ligaments were released (injured, stressed). Measurements were compared by one
      way ANOVA and paired Student's t-test. Intra and inter-observer agreements were
      evaluated by intraclass correlation coefficient (ICC). P-values <.05 were
      considered significant. RESULTS: We found excellent intra-observer (0.97) and
      inter-observer (0.98) agreement following the imaging assessment. Significant
      differences were found in the paired comparison between the groups (p < .05).
      When using an absolute value for TFCS >6 mm as diagnostic for coronal syndesmotic
      instability, the tap test demonstrated a 96.3% sensitivity and specificity, a
      96.3% PPV and NPV and a 96.3% accuracy in diagnosing coronal syndesmotic
      instability. CONCLUSIONS: Our cadaveric study demonstrated that this novel
      coronal syndesmotic instability test using a 3.5 mm blunt cortical tap is a
      simple, accurate and reliable technique able to demonstrate significant
      differences in the tibiofibular clear space when injury was present. It could
      represent a more controlled and stable alternative to the most used Cotton test.

PMID- 30115448
TI  - Immediate surgery or conservative treatment for complicated acute appendicitis in
      children? A meta-analysis.
AB  - PURPOSE: This study carried out a meta-analysis to compare immediate surgery (IS)
      with conservative treatment (CT) of complicated acute appendicitis (CAA) in
      children. METHODS: Systematic literature research was performed for relevant
      studies published from 1969 to date. Trials of IS compared with CT were included.
      Outcomes of interest were postoperative morbidity and length of hospital stay
      (LOS). RESULTS: Fifteen trials were studied (1.243 patients). CT achieved better
      rates of any complication type (odds ratio [OR] 0.22, [95% confidence interval
      (CI): 0.14, 0.38], p = 0.001) and wound infection (OR: 0.40 [95% CI: 0.17, 0.96],
      p = 0.041). Neither intraabdominal abscess (OR: 1.03 [95% CI: 0.31, 3.37], p =
      0.958) nor postoperative ileus (OR: 0.29 [95% CI: 0.06, 1.44], p = 0.130) was
      affected by the treatment option. The polled difference in LOS showed a trend for
      shorter LOS in the IS group (standard mean difference [SMD]: 0.25 [95% CI: 0.07, 
      0.43], p = 0.007). CONCLUSIONS: IS was associated with shorter LOS, while overall
      complication rates and wound infection declined significantly with CT. The
      development of intraabdominal abscess and postoperative ileus was not affected by
      the treatment of choice. The heterogeneity of most studies depicts the need for
      randomized controlled trials (RCTs) to discover safe management of CAA in
      children. LEVEL OF EVIDENCE: III: Type of study: Meta-analysis.

PMID- 30115449
TI  - Congenital prepubic sinus-An aborted dorsal urethral duplication or a cloacal
      remnant?
AB  - BACKGROUND: Congenital Prepubic Sinus (CPS) is an uncommon urogenital anomaly
      characterized by a blind tract between the skin over the pubis to anterior of the
      urinary bladder, Urethra or umbilicus. We report four such cases to emphasize
      varied clinical presentation and embryological conundrum. METHODS: Following
      Ethical Review Committee (ERC) approval, medical records of pediatric patients
      (<16 years) presenting with CPS (identified through operating room records and
      Hospital Information Management System (HIMS) between 1994 and 2018 were reviewed
      for demographics, clinical presentation, investigations including histopathology,
      management and outcome. RESULTS: Four cases of CPS, 3 females and 1 male, age
      range 9 months to 13 years were managed over 25-years. Clinical presentation
      includes a discharging sinus and recurrent episodes of cellulitis and abscess
      formation in pubic area and labia majora. Urological investigations were mostly
      normal. Insertion of lacrimal probe or plastic sheath of intravenous cannula
      through the sinus opening was useful to determine the course of sinus and aid its
      excision. Histology of excised sinus highlights the possible embryological
      origin. CONCLUSIONS: CPS is a rare anomaly with varied clinical presentation. It
      seems CPS is an aborted urethral duplication (Stephen Type 3) or a Cloacal
      remnant. Complete excision of the tract in the reported cases was curative. TYPE
      OF STUDY: Case series. LEVEL OF EVIDENCE: IV.

PMID- 30115451
TI  - Characterizing export of land-based microplastics to the estuary - Part I:
      Application of integrated geospatial microplastic transport models to assess tire
      and road wear particles in the Seine watershed.
AB  - Human and ecological exposure to micro- and nanoplastic materials (abbreviated as
      MP, < 5 mm) occurs in both aquatic and terrestrial environments. Recent reviews
      prioritize the need for assessments linking spatially distributed MP releases
      with terrestrial and freshwater transport processes, thereby providing a better
      understanding of the factors affecting MP distribution to the sea. Tire and road
      wear particles (TRWP) have an estimated generation rate of 1 kg tread inhabitant
      1 year-1 in Europe, but the fate of this MP source in watersheds has not been
      systematically assessed. An integrated temporally and geospatially resolved
      watershed-scale MP modeling methodology was applied to TRWP fate and transport in
      the Seine (France) watershed. The mass balance considers TRWP generation and
      terrestrial transport to soil, air, and roadways, as well as freshwater transport
      processes including particle heteroaggregation, degradation and sedimentation
      within subcatchments. The per capita TRWP mass release estimate in the Seine
      watershed was 1.8 kg inhabitant-1 yr-1. The model estimates indicated that 18% of
      this release was transported to freshwater and 2% was exported to the estuary,
      which demonstrated the potential for appreciable capture, degradation, and
      retention of TRWP prior to export. The modeled pseudo-steady state sediment
      concentrations were consistent with measurements from the Seine watershed
      supporting the plausibility of the predicted trapping efficiency of approximately
      90%. The approach supported the efficient completion of local and global
      sensitivity analyses presented in Part II of this study, and can be adapted to
      the assessment of other MPs.

PMID- 30115452
TI  - Relationship of Patent Ductus Arteriosus Size to Echocardiographic Markers of
      Shunt Volume.
AB  - OBJECTIVE: To define the technique of estimating ductal diameter (DD) that best
      correlates with echocardiographic markers of transductal shunt volume in preterm
      infants >7 days old with persistent patent ductus arteriosus (PDA). STUDY DESIGN:
      We conducted a retrospective study of 104 neonates born at <30 weeks gestation
      that had targeted neonatal echocardiography evaluation of PDA performed between 7
      and 30 days. We used univariate analysis to determine the association of
      echocardiographic markers of shunt volume with ductal size definitions: DD, DD
      indexed to weight, and DD indexed to left pulmonary artery diameter. RESULTS: Two
      hundred echocardiograms were reviewed from 104 patients with a median gestational
      age of 25.4 weeks (range, 25-26.3 weeks) and a median birth weight of 810 g
      (range, 740-920 g). We found a weak correlation of each method of PDA size
      definition with individual echocardiographic markers of transductal shunt volume,
      of which nonindexed DD demonstrated the best correlation. The best correlation
      was found with markers of systemic hypoperfusion, such as diastolic flow reversal
      in the descending aorta (R2 = 0.24) and celiac artery (R2 = 0.21). Markers of
      pulmonary overcirculation, such as left ventricular end-diastolic diameter (R2 =
      0.19) and left ventricular output (R2 = 0.17), showed fair correlation with
      nonindexed DD. CONCLUSION: In preterm infants >7 days old with PDA, nonindexed DD
      demonstrated weak correlations with individual echocardiographic markers of shunt
      volume. These data highlight the need for comprehensive echocardiographic
      evaluation in addition to diameter measurements to provide a better understanding
      of the hemodynamic consequences of PDA.

PMID- 30115450
TI  - [Use of contraception with only progestogens in primary care: Study GESTAGAP].
AB  - AIM: To estimate the prevalence of use of progestin-only contraceptive among
      women who request reversible contraception in Primary Care (PC). DESIGN:
      Multicentre cross-sectional study. SETTING: Primary Care Health Care Centres
      (Madrid). PARTICIPANTS: Women aged 16-50 years old, users of reversible
      contraception, who speak Spanish, and had attended the Primary Care Centre in the
      last year. MAIN MEASUREMENTS: Primary outcome: contraceptive method used:
      Contraception with progestins-only (yes/no). Age, parity, country of origin, type
      of contraceptive method used, reason for choice, source of information,
      satisfaction with the contraceptive method. Telephone survey. RESULTS: A total of
      417 women were interviewed. The median age was 30.3years (SD: 7.7). Spanish 69%,
      and 82% of participants had secondary or university studies. More than half (57%)
      were nulliparous. The type of contraceptive used included: progestins only: 14%,
      combined hormonal contraceptive: 74%, copper IUD: 2%, and condom 10%. The
      prevalence of use of "progestins-only" was 13.9% (95%CI: 10.6-17.2).
      Medroxyprogesterone acetate injection was the most progestin-only method used
      (4.6%), desogestrel oral pill (4.1%), IUD-levonorgestrel IUD (3.9%), and
      etonogestrel subdermal implant (1.9%). The family doctor was the prescriber in
      71% of the women. Satisfaction: high (range 9-10). Using only progestogens was
      associated with older age, being non-Spanish, breastfeeding, and having a medical
      contraindication for combined contraception (P<0.05). CONCLUSIONS: The prevalence
      of use for progestins was 14%, satisfaction was very high for all contraceptive
      methods. The user profile for the only progestins-only corresponds to older, and
      non-Spanish women with conditions such as breastfeeding or contraindications for
      other contraceptives.

PMID- 30115453
TI  - Open Re-rupture of the Achilles Tendon Following Minimally Invasive Repair: A
      Case Report.
AB  - In this report, we describe a rare complication of an open re-rupture of the
      Achilles tendon following a minimally invasive Achilles tendon repair on a
      healthy 29-year-old active male. The reinjury happened 19 weeks following the
      primary surgical repair of a spontaneous rupture, performed by minimally invasive
      technique with the help of a jig using partially absorbable sutures and four
      locking stitches. The wound of the open re-rupture was transverse, in a
      perpendicular orientation relative to the longitudinal approach used in the index
      procedure. Increased scar tissue formation, the absence of an adequate layer of
      paratenon overlying the primary tendon repair, and foreign-body reaction to the
      suture may have been involved in the occurrence of this unusual complication in
      the surgical treatment of Achilles tendon rupture.

PMID- 30115454
TI  - Impact of Regional Nodal Irradiation on the Outcomes of N1 Breast Cancer Patients
      Referred for Adjuvant Treatment: A Patient-Level Pooled Analysis of 2 Clinical
      Trials.
AB  - PURPOSE: To evaluate the impact of regional nodal irradiation (RNI) among N1
      operable breast cancer patients who underwent adequate axillary dissection and
      received adjuvant chemotherapy. PATIENTS AND METHODS: This is a pooled analysis
      of 812 breast cancer patients referred for adjuvant systemic therapy in 2
      prospective randomized studies: NCT00174655 (BIG 02/98) and NCT00312208
      (BCIRG005). Overall survival was assessed according to whether patients received
      supraclavicular and/or internal mammary radiotherapy through Kaplan-Meier
      estimates. Univariate and multivariate analyses of variables affecting overall
      and relapse-free survival were performed through Cox regression analysis.
      Additionally, recurrence rates were analyzed according to regional irradiation
      patterns. RESULTS: Regional relapse rates (after a median follow-up of 76 months)
      were 1.5% in both groups of patients who received or did not receive
      supraclavicular radiotherapy. The risk of regional recurrence was 0.7% in
      patients who received internal mammary node radiotherapy versus 1.6% in patients
      who did not receive internal mammary node radiotherapy. The following factors
      were associated with worse overall survival in multivariate Cox regression
      analysis: age < 40 years (P < .0001), > T1 stage (P = .003), and negative hormone
      receptor status (P = .002). Neither supraclavicular nor internal mammary
      radiotherapy was associated with improvement in overall or relapse-free survival
      in Cox regression analysis. CONCLUSION: The current analysis does not endorse the
      routine use of supraclavicular or internal mammary radiotherapy among N1 operable
      breast cancer patients who have undergone adequate dissection of axillary lymph
      nodes and who have received standard adjuvant systemic therapy. Given the limited
      power and potential selection bias of the current analysis, further prospective
      studies are needed to tackle this research question.

PMID- 30115456
TI  - Impacted intrahepatic stone: Laparoscopic-endoscopic approach using flexible
      cholangioscopy.

PMID- 30115455
TI  - Utility of standardized discharge criteria after appendectomy to identify
      pediatric patients requiring intervention after postoperative imaging.
AB  - BACKGROUND: The purposes of this study were to evaluate the efficacy of failure
      of-discharge criteria and identify the cohort of pediatric patients after
      appendectomy in whom postoperative imaging would impact management. METHODS:
      Pediatric patients who underwent an appendectomy from July 2009 to May 2017 were
      included. Complicated appendicitis was defined based on the intraoperative
      diagnosis. Postoperative imaging was recommended at postoperative days 5-7 for
      patients who met at least one criterion of failure of standard management: fever
      (>38 degrees C), leukocytosis (white blood cell count >12,000/mm3), diet
      intolerance, or uncontrolled pain by oral analgesics at postoperative day 5.
      Primary outcomes included any intervention (reoperation, drainage procedures, or
      change in antibiotics). RESULTS: In all, 3,276 pediatric patients undergoing
      appendectomy were identified. Of these patients, 12% met at least 1 discharge
      criterion of failure Most discharge failures (79%) underwent postoperative
      imaging, such as computed tomography (68%), ultrasonography then computed
      tomography (20%), or ultrasonography only (12%); 39% of imaging patients required
      intervention. On multiple logistic regression, 3 criteria (diet intolerance,
      fever, and leukocytosis), complicated disease, and age were associated with the
      need for intervention after imaging. The type of imaging modality did not
      discriminate need for intervention. CONCLUSION: Standardized criteria identifying
      failure of ability to discharge the patient after appendectomy limits the need
      for unnecessary imaging. In the management of pediatric appendicitis, a selective
      approach resulted in a high yield of complications requiring intervention after
      obtaining postoperative imaging.

PMID- 30115457
TI  - Introducing new and emerging genetic tests into prenatal care.
AB  - Given the rapid advances in genomics, translating new genomic tests effectively
      into prenatal clinical practice remains challenging. We discuss emerging genetic
      tests, considerations for their use, how tests should ideally be validated prior
      to use in clinical practice, and the role of the Federal Drug Administration,
      Clinical Laboratory Improvement Amendments (CLIA) laboratories, commercial
      laboratories, insurers, and professional societies such as the American College
      of Obstetricians and Gynecologists (ACOG), and the Society for Maternal-Fetal
      Medicine (SMFM) in the introduction of new prenatal genetic tests. After the
      introduction of new tests into the prenatal clinic, it is critical to utilize
      shared databases with measured outcomes to improve clinical care as well as to
      advance science.

PMID- 30115458
TI  - Indications for partial parotidectomy using retrograde dissection of the marginal
      mandibular branch of the facial nerve for benign tumours of the parotid gland.
AB  - The aims of this study were to evaluate the efficacy of partial parotidectomy
      using retrograde dissection of the marginal mandibular branch of the facial nerve
      for benign tumours of the parotid gland and to establish the indications for its
      use. We examined 106 consecutive patients with previously untreated benign
      tumours in the lower portion of the parotid gland who were treated by
      parotidectomy. The first group (anterograde group, n=52) consisted of those who
      had standard anterograde parotidectomy. The remaining patients, who underwent
      retrograde parotidectomy, were further divided into two groups: those in whom the
      upper edge of the tumour was located below the mastoid tip (below mastoid group,
      n=46) or those in whom it was above the mastoid tip (above mastoid group, n=8).
      The operating time was significantly shorter in the below mastoid group (141.2,
      127.5, and 98.1minutes, respectively) as was intraoperative blood loss (41.1,
      53.0, and 24.4ml, respectively), compared with the other two groups. There was a
      higher incidence of facial nerve dysfunction in the above mastoid group
      postoperatively (4/8) than in the other two groups. The results suggested that
      the presence of a tumour of any size located below the mastoid tip is a good
      indication for parotidectomy using retrograde dissection of the marginal
      mandibular branch of the facial nerve.

PMID- 30115459
TI  - Condylar hyperplasia: current thinking.
AB  - Unilateral condylar hyperplasia is a rare disease that causes facial asymmetry as
      a result of excessive vertical or horizontal growth, or both, of the mandibular
      condyle. Investigation should address the patient's concerns, and establish
      whether the disease is active with the use of single positron emission tomography
      (PET). Proportional reduction of the condyle arrests active disease and restores
      mandibular height, and any residual asymmetry can be corrected according to
      conventional orthognathic principles. We recommend the use of 3-dimensional
      virtual planning for such complex movements. The rarity of the disease means
      that, to our knowledge, high-quality evidence is lacking and further research is
      needed.

PMID- 30115460
TI  - Effectiveness of nutritional interventions in older adults at risk of
      malnutrition across different health care settings: Pooled analyses of individual
      participant data from nine randomized controlled trials.
AB  - BACKGROUND & AIMS: Protein-energy malnutrition is a health concern among older
      adults. Improving nutritional status by increasing energy and protein intake
      likely benefits health. We therefore aimed to investigate effects of nutritional
      interventions in older adults (at risk of malnutrition) on change in energy
      intake and body weight, and explore if the intervention effect was modified by
      study or participants' characteristics, analysing pooled individual participant
      data. METHODS: We searched for RCTs investigating the effect of dietary
      counseling, oral nutritional supplements (ONS) or both on energy intake and
      weight. Principle investigators of eligible studies provided individual
      participant data. We investigated the effect of nutritional intervention on
      meaningful increase in energy intake (>250 kcal/day) and meaningful weight gain
      (>1.0 kg). Logistic generalized estimating equations were performed and ORs with
      95% CIs presented. RESULTS: We included data of nine studies with a total of 990
      participants, aged 79.2 +/- 8.2 years, 64.5% women and mean baseline BMI 23.9 +/-
      4.7 kg/m2. An non-significant intervention effect was observed for increase in
      energy intake (OR:1.59; 95% CI 0.95, 2.66) and a significant intervention effect
      for weight gain (OR:1.58; 95% CI 1.16, 2.17). Stratifying by type of
      intervention, an intervention effect on increase in energy intake was only
      observed for dietary counseling in combination with ONS (OR:2.28; 95% CI 1.90,
      2.73). The intervention effect on increase in energy intake was greater for
      women, older participants, and those with lower BMI. Regarding weight gain, an
      intervention effect was observed for dietary counseling (OR:1.40; 95% CI 1.14,
      1.73) and dietary counseling in combination with ONS (OR:2.48; 95% CI 1.92,
      3.31). The intervention effect on weight gain was not influenced by participants'
      characteristics. CONCLUSIONS: Based on pooled data of older adults (at risk of
      malnutrition), nutritional interventions have a positive effect on energy intake
      and body weight. Dietary counseling combined with ONS is the most effective
      intervention.

PMID- 30115462
TI  - Cost analysis of chronic intestinal failure.
AB  - BACKGROUND & AIMS: Chronic intestinal failure is a complex medical condition
      which is associated with high costs. These patients require long-term home
      parenteral nutrition (HPN) and costs are compounded by frequent admissions for
      the underlying disease and HPN. However, it is unknown what the specific costs
      subdivisions are and how they evolve over time. The aim of the study was to
      evaluate the cost dynamics of HPN care in a cohort of stable, long-term
      intestinal failure patients. METHODS: A retrospective analysis of our single
      center long-term (>2 years), benign HPN population was performed. All relevant
      clinical and financial data were collected: costs of hospital admissions,
      diagnostics, treatments, out-patient clinics, home care, medication, materials
      and HPN education. The costs were tabulated and assigned by cause (HPN related,
      underlying disease-related or -unrelated). Patients with complicated intestinal
      failure (defined as impending loss of vascular access, liver failure or recurrent
      fluid/electrolyte disorders) were excluded. Data are presented as median (range).
      RESULTS: Thirty-seven patients (24 female; age 58.6 +/- 13.3 years) were included
      in the study. HPN duration was 5.3 years (2.1-15.1) at 4.3 infusion days per week
      (1.5-7). Total cost of the first HPN year was ?83,503 (35,364-256,780). HPN
      related costs accounted for 69% (?57,593) vs 27% for underlying disease-related
      costs (?22,505) and 4% for disease-unrelated costs (?3065). HPN complications
      cost ?16,077 in the first year and accounted for 31% of HPN costs. The total cost
      dropped by 15% in the second year to ?71,311. This reduction was due to fewer
      hospital admissions and fewer HPN complications. This trend continued and by year
      5 the annual cost was 40% cheaper compared to year 1 (?58,187 vs ?83,503).
      CONCLUSIONS: HPN related costs accounted for the majority of the total expenses
      in IF patients. The costs declined after the first year due to a reduction in
      complications and hospital admissions.

PMID- 30115464
TI  - Is Point-of-Care Ultrasonography Effective for the Diagnosis of Urolithiasis?

PMID- 30115463
TI  - [Importance of preoperative guided ultrasound in patients with femoral fracture -
      Case report].
AB  - OBJECTIVE: The aim of this report is to represent the role of the use of bedside
      ultrasound by the anesthesiologist, offering an individualized approach to the
      specific condition of the patient, without unnecessary postponement of femur
      fracture surgical repair in the elderly. CASE REPORT: Female patient, 86 years
      old, hypertensive, victim of trochanteric fracture of the femur, taken to the
      operating room after being released by cardiology service. A bedside ultrasound
      exam allowed the identification of aortic stenosis, left ventricular hypertrophy,
      carotid stenosis, and signs of hypovolemia. From these findings, it was decided
      to use an ultrasound-guided block of the nerves femoral and lateral cutaneous of
      the thigh as an anesthetic technique. CONCLUSIONS: The use of ultrasound guidance
      by the anesthesiologist can provide relevant information for individualizing the
      anesthetic technique, without postponing the surgical intervention, which usually
      occurs when the patient is referred for complete examination by the specialist.

PMID- 30115461
TI  - An international study of the quality of life of adult patients treated with home
      parenteral nutrition.
AB  - BACKGROUND & AIMS: Home parenteral nutrition-quality of life (HPN-QOL(c)) is a
      self-assessment tool for the measurement of QOL in patients on HPN. The aims of
      this study were: to re-assess the basic psychometric properties of the HPN-QOL(c)
      in a multinational sample of adult patients; to provide a description of QOL
      dimensions by short and long HPN treatment duration; to explore clinical factors
      potentially associated to QOL scores. METHODS: Patients (n = 699) from 14
      countries completed the HPN-QOL(c). The questionnaires were analysed to evaluate
      data completeness, convergent/discriminant validity and internal-consistency
      reliability. The association of overall QOL and HPN treatment duration as well as
      other clinical factors were investigated using multivariable linear regression
      models. RESULTS: The analysis of the multitrait-scaling and internal consistency
      indicates a good fit with the questionnaire structure for most items. Item
      discriminant validity correlation was satisfactory and psychometric evaluation of
      the HPN-QOL(c) in the different English, French and Italian language patient sub
      groups confirmed psychometric equivalence of the three questionnaire versions.
      The results of the multivariable linear regression showed that QOL scores were
      significantly associated with HPN duration (better in long-term), underlying
      disease (better in Crohn's disease and mesenteric ischaemia) and living status
      (worse in living alone) and, after adjusting for the other factors, with the
      number of days of HPN infusion per week. CONCLUSIONS: The HPN-QOL(c), is a valid
      tool for measurement of QOL in patients on HPN, to be used in the clinical
      practice as well as in research.

PMID- 30115465
TI  - What Is the Accuracy of Physical Examination, Imaging, and the LRINEC Score for
      the Diagnosis of Necrotizing Soft Tissue Infection?

PMID- 30115466
TI  - Radiation-induced nasopharyngeal ulcers after intensity modulated radiotherapy in
      primary nasopharyngeal carcinoma patients: A dose-volume-outcome analysis.
AB  - OBJECTIVE: This is a retrospective dose-volume-outcome analysis of radiation
      induced nasopharyngeal ulcers after intensity modulated radiotherapy in primary
      nasopharyngeal carcinoma (NPC) patients, with the aim to determine how the
      radiation doses to nasopharynx influence the occurence of radiation-induced
      nasopharyngeal ulcer (RINU) and predict the most serious complication of
      radiotherapy for NPC. METHODS: Data from 6023 consecutive and nonselected
      histologically proven primary NPC patients treated with definitive IMRT were
      collected and 25 patients were diagnosed with nasopharyngeal ulcer and met the
      diagnosis criteria of RINU. Predictive dosimetric factors were identified by
      using univariate and multivariate analysis. RESULTS: Paired samples t-tests
      showed all dosimetric factors were significantly correlated with the development
      of RINU, and these factors were associated with each other closely. (P < 0.001)
      Multivariate analysis revealed D3cc (dose to 3 mL of the nasopharynx) was an
      independent predictor for RINU (P = 0.01); the area under the ROC curve for D3cc
      was 0.87 (P < 0.001), and the cutoff point 73.67 Gy may be the dose tolerance of
      the nasopharynx. The primary tumor location, distribution of high dose regions
      and the location of RINU were consistent. CONCLUSIONS: The study indicates that
      radiation-induced nasopharyngeal ulcer is consistent with primary tumor location
      and 'hottest spots' regions and we suggest a D3cc limit of 73.67 Gy for the
      nasopharynx. Physicians should be cautious of such 'hot spots' in the
      nasopharynxduring IMRT treatment plan optimization, review and approval to avoid
      the most serious complication of radiotherapy for NPC.

PMID- 30115467
TI  - Clarithromycin as the empiric antibiotic therapy for medication-related
      osteonecrosis of the jaw in multiple myeloma patients.
AB  - About half of individuals diagnosed with medication-related osteonecrosis of the
      jaw (MRONJ) are multiple myeloma (MM) patients, and most are treated using
      antibiotics for long-term courses. The penicillin group is recommended as the
      empiric drug of choice, and quinolones, metronidazole, clindamycin, doxycycline,
      and erythromycin as alternatives. This paper suggests the macrolide
      clarithromycin as the empiric antibiotic therapy of MRONJ in MM patients because
      of its better pharmacologic properties in comparison to erythromycin, and the
      beneficial effect of this agent in MM. This empiric antibiotic regimen should be
      later adjusted according to the response and findings of the microbial cultures.

PMID- 30115468
TI  - Age and adenoma size are independent risk factors for the development of
      carcinoma ex pleomorphic adenoma.

PMID- 30115469
TI  - Clinical outcomes with therapies for previously treated recurrent/metastatic head
      and-neck squamous cell carcinoma (R/M HNSCC): A systematic literature review.
AB  - OBJECTIVES: A wide range of objective response rates (ORRs: 0-53%) among
      available treatments in patients with R/M HNSCC with progression on or after
      platinum-based chemotherapy (PBT) renders treatment selection a challenge. This
      systematic literature review (SLR) was intended to aid clinical decision-making
      by classifying historical studies to accurately characterize the response in
      second-line (progression on/after platinum-based therapy), and third-line
      (progression on/after platinum and cetuximab/other drug) settings. METHODS: SLR
      was performed to characterize the ORR, duration of response (DOR), progression
      free survival (PFS) and overall survival (OS) with therapies recommended by the
      National Comprehensive Cancer Network (NCCN) guidelines. Clinical trials
      published in English between January 1, 1985, and September 30, 2016 were
      identified by searching the PubMed (Medline), Cochrane, and Embase databases.
      RESULTS: The SLR identified 34 key studies in second-line R/M HNSCC patients, and
      one of these included a third-line patient cohort. However, several studies did
      not enrol a strictly second-line population. Response in a true second-line
      setting was elucidated by categorizing the studies using a novel framework
      defined according to the extent to which enrolled patients were second-line. Only
      seven studies were strictly second-line, with an estimated pooled ORR of 4% (95%
      CI = 2-8%; N = 414) for methotrexate and 11% (95% CI = 7-15%; N = 235) for
      cetuximab, and a reported ORR of 14% (N = 78) from a single study of paclitaxel.
      The median DOR was limited with cetuximab (~4 months) and paclitaxel (~7 months),
      and not reported for methotrexate. Median PFS or time to progression (TTP) ranged
      from 1.7 to 3.5 months, and median OS from 4.3 to 6.7 months. The ORR in the only
      third-line study was 0% (95% CI = 0-7; N = 53) for the platinum + cetuximab
      combination. CONCLUSION: These findings emphasize the historically bleak
      prognoses in patients with R/M HNSCC following PBT progression. Anti-PD-1
      therapies, namely pembrolizumab and nivolumab, represent novel treatment options
      that may improve clinical outcomes.

PMID- 30115470
TI  - Survival impact and toxicity of metformin in head and neck cancer: An analysis of
      the SEER-Medicare dataset.
AB  - OBJECTIVES: Recent preclinical research has renewed interest in the interplay
      between glucose dysregulation and cancer. Metformin holds promise as an
      adjunctive antineoplastic agent in head and neck cancer (HNC). We aimed to
      explore the impact of metformin in HNC patients from a population-based dataset.
      PATIENTS & METHODS: Patients diagnosed with HNC from 2008 to 2011 were identified
      from the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked
      dataset and categorized into three groups: non-diabetics (nD), diabetics not
      taking metformin (DnM), and diabetics taking metformin (D + M). Overall survival
      (OS) and cancer-specific survival (CSS) were compared between groups using Kaplan
      Meier and Cox regression controlling for sociodemographic, clinical, and
      treatment covariates. The incidence of toxicities associated with HNC therapy was
      compared among groups using chi2 analysis. RESULTS: Among 1646 patients, there
      were 1144 nD, 378 DnM, and 124 D + M. 2-year OS rates was 65.6% for nD, 57.7% for
      DnM, and 73.4% for D + M by Kaplan-Meier (p < 0.01), and corresponding rates of 2
      year CSS were 73.7%, 66.1%, and 88.8% (p < 0.01), respectively. On Cox
      multivariable analysis, OS among the three groups did not significantly differ;
      however, CSS was significantly worse among both nD versus DnM as compared to D +
      M. Toxicity rates were not significantly increased among D + M. CONCLUSION: HNC
      patients with diabetes taking metformin experience improved CSS. Prospective
      investigation of the addition of metformin to standard-of-care HNC therapy is
      warranted.

PMID- 30115471
TI  - Clinical analysis of second primary gingival squamous cell carcinoma after
      radiotherapy.
AB  - INTRODUCTION: Clinically, we have observed that some oral cancer patients have a
      history of radiotherapy for head and neck cancer; we have named this condition
      radiotherapy-associated cancer (RAC). Gingival cancer, which is usually
      juxtaposed with other oral cancer subtypes, is seldom reported individually, and
      there are few reports on the association between the incidence of oral cancer and
      history of radiation therapy. Therefore, this study aimed to elucidate the
      clinicopathological features and prognosis of second primary gingival squamous
      cell carcinoma after head and neck radiotherapy. MATERIALS AND METHODS: The data
      collected included 450 patients diagnosed with gingival squamous cell carcinoma
      from 1964 to 2012 at Sun Yat-sen University Cancer, among whom 52 patients had a
      history of radiotherapy for head and neck cancer. We retrospectively analysed the
      differences in the clinicopathological characteristics and prognosis between
      sporadic gingival squamous cell carcinoma and radiation-associated gingival
      carcinoma, with an emphasis on gingival carcinoma. RESULTS: Sporadic gingival
      squamous cell carcinoma is less likely to have more advanced T stage, and the
      second primary tumour is more likely to be located in the molar area of the
      maxillary gingiva than in the mandibular gingiva (75.6% vs 24.4%, P < 0.05). The
      5-year overall survival of patients with second primary gingival carcinoma was
      influenced by age distribution, T classification, N classification, clinical TNM
      stage, histological grade and radiation history in head and neck. Mandibular
      gingival carcinoma was more likely to have an increased neck lymph node
      metastasis than maxillary gingival carcinoma (P = 0.001), but there was no
      significant difference in 5-year overall survival between these two groups (P =
      0.828). The main therapy for gingiva carcinoma is surgery or comprehensive
      treatment based on surgery. CONCLUSIONS: Second primary gingival squamous cell
      carcinoma after radiotherapy demonstrated particular clinicopathologic features,
      such as prominent sites and TNM stage; and there was statistically significant
      difference in 5-year overall survival and prognosis between second primary
      gingival carcinoma after radiotherapy and sporadic gingival carcinoma.

PMID- 30115473
TI  - Salivary exosomes as potential biomarkers in cancer.
AB  - Over the past decade, there has been emerging research in the field of
      extracellular vesicles, especially those originating from endosomes, referred to
      as 'exosomes. Exosomes are membrane-bound nanovesicles secreted by most cell
      types upon fusion of multivesicular bodies (MVBs) to the cell plasma membrane.
      These vesicles are present in almost all body fluids such as blood, urine,
      saliva, breast milk, cerebrospinal and peritoneal fluids. Exosomes participate in
      intercellular communication by transferring the biologically active molecules
      like proteins, nucleic acids, and lipids to neighboring cells. Exosomes are
      enriched in the tumour microenvironment and growing evidence demonstrates that
      exosomes mediate cancer progression and metastasis. Given the important
      biological role played by these nanovesicles in cancer pathogenesis, these can be
      used as ideal non-invasive biomarkers in detecting and monitoring tumours as well
      as therapeutic targets. The scope of the current review is to provide an overview
      of exosomes with a special focus on salivary exosomes as potential biomarkers in
      head and neck cancers.

PMID- 30115472
TI  - Prospective evaluation of patient reported swallow function with the Functional
      Assessment of Cancer Therapy (FACT), MD Anderson Dysphagia Inventory (MDADI) and
      the Sydney Swallow Questionnaire (SSQ) in head and neck cancer patients.
AB  - OBJECTIVES: The Functional Assessment of Cancer Therapy (FACT) instrument is
      comprised of a group of related and overlapping quality of life (QoL)
      questionnaires including a core general form, head and neck cancer (HNC)-specific
      items, and an expert-selected index (FACT-HNSI). Understanding how these relate
      to more HNC-specific instruments such as the MD Anderson Dysphagia Inventory
      (MDADI) and Sydney Swallow Questionnaire (SSQ) is vital for guiding their use in
      clinical trials. MATERIALS AND METHODS: HNC patients concurrently completed
      MDADI, SSQ, and FACT questionnaires at radiation oncology clinic visits (2015
      2016). Spearman correlation coefficients were calculated between each FACT
      instrument and MDADI or SSQ. Unsupervised k-means cluster analyses were performed
      to identify clusters of similar QoL responses. Principal component analysis (PCA)
      identified the degree of variability explained by each instrument. RESULTS: We
      identified 631 instances (363 patients) where the questionnaires were completed
      concurrently. Correlations between the various FACT measures and SSQ or MDADI
      were all significant (p < 0.001), but FACT HNC-specific subscale and FACT-HNSI
      showed the strongest correlation with MDADI and SSQ. Clustering identified 3
      distinct groups of responses when combining instruments either pairwise or three
      way. PCA revealed that MDADI and FACT HNC-specific subscale provide similar and
      likely redundant information. CONCLUSION: FACT HNC-subscale and FACT-HNSI may be
      preferable over other FACT measures for use in clinical trials where patient
      reported swallow function is evaluated. MDADI and FACT provide similar insights
      into HNC patient QoL while SSQ provides additional, complementary information
      which could serve to better stratify patients into groups with high, medium, and
      low QoL outcomes.

PMID- 30115474
TI  - Low versus high activity radioiodine remnant ablation for differentiated thyroid
      carcinoma with gross extrathyroidal extension invading only strap muscles.
AB  - OBJECTIVES: The efficacy of radioiodine remnant ablation (RRA) for patients with
      differentiated thyroid carcinoma (DTC) with gross extrathyroidal extension (ETE)
      is well described in observational studies. However, its role in gross ETE
      invading only strap muscles, T3b category in the newly proposed eighth edition of
      the TNM staging system, is currently unknown. METHODS: This study retrospectively
      analyzed 260 DTC patients with ETE invading only strap muscles who underwent
      thyroidectomy at a tertiary Korean hospital between 1994 and 2005. Cancer
      specific survival (CSS) and recurrence-free survival (RFS) in the no RRA (n =
      13), low RRA activity (<3.7 GBq, n = 80), and high RRA activity (>=3.7 GBq, n =
      167) groups were studied. RESULTS: No significant differences were observed
      between low and high activity RRA groups in terms of 10-year CSS (97.3% versus
      99.3%; HR 0.23, 95% CI 0.02-2.57; p = .235) and RFS (86.8% versus 88.8%; 0.90,
      0.40-2.03; p = .804). In the no RRA group, no patients died of cancer, and only
      one developed structural recurrence. In Cox regression analyses with inverse
      probability of treatment weighting adjusted for clinicopathologic risk factors,
      high activity RRA was not related to recurrence outcomes compared to low activity
      (HR 0.60, 95% CI 0.26-1.35; p = .214). CONCLUSIONS: Long term oncologic outcomes
      did not significantly differ between low versus high activity RRA groups, which
      suggests that low activity RRA might be sufficient in patients with DTC with
      gross ETE invading only strap muscles. Further studies are needed to clarify the
      optimal activity of RRA in these patients.

PMID- 30115475
TI  - Induction chemotherapy with carboplatin, nab-paclitaxel and cetuximab for at
      least N2b nodal status or surgically unresectable squamous cell carcinoma of the
      head and neck.
AB  - BACKGROUND: Although induction studies of TPF in SCCHN have not improved outcomes
      compared to chemoradiotherapy alone, phase II studies of weekly carboplatin
      (CbP), paclitaxel and cetuximab (C225) have shown promising results. Nano-albumin
      paclitaxel (nab-paclitaxel) based chemotherapy has demonstrated a higher response
      rate (RR) than solvent-based paclitaxel in squamous cell carcinoma of the lung
      with favorable toxicity. MATERIALS AND METHODS: Patients with treatment naive
      SCCHN of any site with >=N2b disease or that was unresectable by strict criteria
      were eligible. Patients were treated with nab-paclitaxel 100 mg/m2, CbP area
      under the curve (AUC) 2 and C225 400 mg/m2 week 1 then 250 mg/m2 for six weeks,
      followed by standard of care chemoradiotherapy (CRT). The primary endpoint was
      clinical response rate to induction therapy as defined by RECIST version 1.1.
      Secondary measures included toxicity, progression-free survival, overall survival
      and quality of life as measured by FACT-HN. RESULTS: 38 eligible subjects were
      treated. Primary sites were: oropharynx (OPX) (25), larynx (3) oral cavity (OC)
      (9), hypopharynx (1). The most common grade 3 or 4 toxicity during induction was
      acneiform rash (26%) followed by neutropenia (16%). RR was 76.3%. Median PFS and
      OS have not been reached (median follow-up of 3.3 years); they were superior in
      patients with response. CONCLUSIONS: The combination of nab-paclitaxel, CbP and
      C225 is feasible, tolerable and active against locally advanced SCCHN.

PMID- 30115476
TI  - Accuracy of computer-assisted surgery in mandibular reconstruction: A systematic
      review.
AB  - Computer-assisted surgery (CAS) for mandibular reconstruction was developed to
      improve conventional treatment methods. In the past years, many different
      software programs have entered the market, offering numerous approaches for
      preoperative planning and postoperative evaluation of the CAS process of
      mandibular reconstruction. In this systematic review, we reviewed planning and
      evaluation methods in studies that quantitatively assessed accuracy of mandibular
      reconstruction performed with CAS. We included 42 studies describing 413
      mandibular reconstructions planned and evaluated using CAS. The commonest
      software was Proplan/Surgicase CMF (55%). In most cases, the postoperative
      virtual 3-dimensional model was compared to the preoperative 3-dimensional model,
      revised to the virtual plan (64%). The commonest landmark for accuracy
      measurements was the condyle (54%). Accuracy deviations ranged between 0 mm and
      12.5 mm and between 0.9 degrees  and 17.5 degrees . Because of a lack of
      uniformity in planning (e.g., image acquisition, mandibular resection size) and
      evaluation methodologies, the ability to compare postoperative outcomes was
      limited; meta-analysis was not performed. A practical and simple guideline for
      standardizing planning and evaluation methods needs to be considered to allow
      valid comparisons of postoperative results and facilitate meta-analysis in the
      future.

PMID- 30115477
TI  - Cellular-based immunotherapy in Epstein-Barr virus induced nasopharyngeal cancer.
AB  - Undifferentiated Nasopharyngeal carcinoma (NPC) is ubiquitously identified with
      the Epstein-Barr virus (EBV), making this cancer a suitable candidate for
      cellular-based immunotherapy (CBI) due to its expression of potentially
      targetable tumor-associated viral antigens. Various preclinical and clinical
      studies have explored the use of cytotoxic T cells (CTLs), tumor-infiltrating
      lymphocytes (TILs), natural killer (NK) cells, and dendritic cells (DCs) in the
      treatment of both refractory and locally advanced NPC with some success. Notably,
      immune-mediated antitumor effects were observed even in heavily pre-treated NPC
      patients, suggesting potential clinical benefit of CBI in this group of patients.
      These immune anti-tumor effects may be even more clinically evident when used as
      a first-line treatment, since there may not be an intense immunosuppressive
      environment which is typically encountered in refractory cancer patients.
      Additionally, CBI may exert an effect in priming the immune system and
      diminishing the cancer's acquired resistance to exert a more robust response to
      previously failed chemotherapy. Although these results are encouraging, further
      refinements of clinical protocols to boost anti-tumor response and benefit a
      larger subset of patients proved necessary. Herein, we aim to review the rational
      of developing CBI in EBV-induced NPC and summarize its current applications in
      clinical studies.

PMID- 30115478
TI  - Oral tongue carcinoma among young patients: An analysis of risk factors and
      survival.
AB  - INTRODUCTION: The incidence of oral tongue squamous cell carcinoma (OTSCC) in
      younger adults has rapidly increased over the past two decades. While tobacco and
      alcohol use may be less likely to cause these tumors, it remains controversial
      whether differences also exist in their prognosis. Our aim is to examine the risk
      factors for cancer among young (<45 years old) OTSCC patients at our institution,
      and to compare their recurrence and survival with older patients in a matched
      cohort. MATERIALS AND METHODS: All OTSCC patients seen at our institution between
      2000 and 2015 were reviewed. Patients under 45 who with sufficient treatment
      information were matched 1:1 on race, T-stage, and N-stage with patients 45 and
      older. Three-year recurrence and survival were determined in stratified and
      adjusted Cox regression models. RESULTS: Of 397 OTSCC patients were seen at our
      institution, 117 (29%) were less than 45 years old. Younger patients were
      significantly more likely to be female, (50% vs. 39%; p = 0.04) and to abstain
      from tobacco (51% vs. 39%; p < 0.01). Young patients in the matched cohort were
      significantly more likely to have a recurrence (HR 3.9 95% CI 1.4-10.5). There
      was no difference in overall survival. CONCLUSION: Younger OTSCC patients in a
      matched cohort were more likely to recur within 3 years, although there was no
      difference in overall mortality. Differences in risk factors and recurrence
      between older and younger patients suggest that some cancer among younger
      patients may be distinct from traditional OTSCC.

PMID- 30115479
TI  - Survival benefit of post-operative chemotherapy for intermediate-risk advanced
      stage head and neck cancer differs with patient age.
AB  - OBJECTIVES: The National Comprehensive Cancer Network (NCCN) guidelines state
      that surgical patients with advanced-stage head and neck cancer (HNC) and risk
      factors other than extranodal extension (ENE) or positive margins should consider
      post-operative chemoradiation (POCRT). The goal of our study was to determine if
      POCRT is associated with overall survival (OS) compared with post-operative
      radiation therapy (PORT) and whether this varies with patient age. MATERIAL AND
      METHODS: We conducted a retrospective study of 5319 adult patients with stage III
      IV HNC who received primary surgical treatment with POCRT or PORT in the National
      Cancer Database (2010-2013). Patients with distant metastases, ENE, and positive
      margins were excluded. Intermediate risk features included pT3-T4, pN2-N3
      disease, and lymphovascular invasion. Our main outcome was overall survival (OS).
      Statistical analysis included chi-squared tests and Cox proportional hazards
      regressions. RESULTS: On multivariable analysis for non-oropharyngeal cancer
      patients <70 years, POCRT was associated with improved OS for T1-4N2-3 disease
      (hazard ratio [HR], 0.73, 95% confidence interval [CI]; 0.58-0.93) but was not
      associated with OS for T3-4N0-1 disease (HR, 0.92; 95% CI, 0.71-1.19). For
      patients >=70 years, POCRT was not associated with improved OS for patients with
      T1-4N2-3 disease (HR, 1.21; 95% CI, 0.79-1.86) or T3-4N0-1 disease (HR, 1.08; 95%
      CI, 0.71-1.65). For oropharyngeal cancer patients with HPV-positive disease,
      POCRT was associated with decreased OS (HR, 9.52; 95% CI, 2.38-38.08).
      CONCLUSION: Chemoradiation may offer a survival benefit for non-oropharyngeal
      intermediate-risk advanced-stage HNC patients <70 years of age with T1-4N2-3
      disease, but may not benefit those >=70 years of age or those with T3-4N0-1
      disease.

PMID- 30115480
TI  - Communication of prognosis in head and neck cancer patients; a descriptive
      qualitative analysis.
AB  - OBJECTIVES: In shared decision making it is important to adequately, timely and
      actively involve patients in treatment decisions. Sharing prognostic information
      can be of key importance. This study describes whether and how prognostic
      information on life expectancy is included during communication on diagnosis and
      treatment plans between physicians and head and neck (H&N) oncologic patients in
      different phases of disease. METHODS: A descriptive, qualitative study was
      performed of n = 23 audiotaped physician-patient conversations in which both
      palliative and curative treatment options were discussed and questions on
      prognosis were expected. Verbatim transcribed consultations were systematically
      analyzed. A distinction was made between prognostic information that was provided
      (a) quantitatively: by giving numerical probability estimates, such as
      percentages or years or (b) qualitatively: through the use of words such as 'most
      likely' or 'highly improbable'. RESULTS: In all consultations, H&N surgeons
      provided some prognostic information. In 5.9% of the provided prognostic
      information, a quantitative method was used. In 94.1% prognostic information was
      provided qualitatively, using six identified approaches. H&N surgeons possibly
      affect patients' perception of prognostic content with two identified
      communication styles: directive (more physician-centered) and affective (more
      patient-centered). CONCLUSION: This study is first in providing examples of how
      H&N surgeons communicate with their patients regarding prognosis in all stages of
      disease. They often exclude specific prognostic information. The study outcomes
      can be used as a first step in developing a guideline for sharing prognostic
      information in H&N oncologic patients, in order enable the process of shared
      decision making.

PMID- 30115481
TI  - Staging HPV-related oropharyngeal cancer: Validation of AJCC-8 in a surgical
      cohort.
AB  - IMPORTANCE: The American Joint Committee on Cancer, 8th edition (AJCC-8) contains
      a new staging system for human papillomavirus (HPV)-related oropharyngeal
      squamous cell carcinoma (OPSCC). Our study aim was to evaluate the effectiveness
      of the AJCC-8 relative to the AJCC 7th edition (AJCC-7). MATERIALS AND METHODS: A
      retrospective chart review was performed on a multi-institutional, prospectively
      collected dataset from two tertiary referral centers. All patients had HPV+ OPSCC
      treated primarily with surgery. The prognostic value of AJCC-7 and AJCC-8 were
      compared for 5-year overall survival (OS) and disease-specific survival (DFS).
      RESULTS: AJCC-8 pathological staging effectively risk stratified patients,
      creating a Cox model with a better fit (lower Akaike's Information Criterion, p <
      0.0001) when compared to AJCC-7 pathological stages for both OS and DFS. The AJCC
      8 pathologic staging did not produce a better fit than the AJCC-8 clinical
      staging (p = 0.15) for OS, however, AJCC-8 pathologic was more effective than
      AJCC-8 clinical for DFS (p < 0.0001). 76% of patients did not change their stage
      between clinical and pathologic AJCC-8 staging; 14% were upstaged by 1, <1% were
      upstaged by 2, 7% were downstaged by 1, and 3% downstaged by 2. CONCLUSIONS AND
      RELEVANCE: The new AJCC-8 staging system represents a significant improvement
      over AJCC-7 for risk stratification into groups that predict overall survival and
      disease-specific survival of surgically treated HPV+ OPSCC patients. The AJCC- 8
      pathologic staging system was not significantly better than the AJCC-8 clinical
      staging system for overall survival, however, the pathologic staging system was
      better than the clinical for disease free survival.

PMID- 30115482
TI  - Self-reported oral morbidities in long-term oropharyngeal cancer survivors: A
      cross-sectional survey of 906 survivors.
AB  - OBJECTIVE: The purpose of this study is to estimate the prevalence and severity
      of late oral morbidities in disease-free oropharyngeal cancer (OPC) survivors
      using patient reported outcomes. MATERIALS AND METHODS: Cross-sectional
      survivorship survey of patients who completed definitive treatment for
      oropharyngeal carcinoma  > 12-months previously without evidence of recurrence,
      second primary malignancy, or distant metastasis after index cancer. Using MD
      Anderson Symptom Inventory- Head and Neck Module (MDASI-HN), scores for 4 self
      reported oral morbidities: dry mouth, mucus secretions, mouth and throat sores,
      and teeth and gum issues were evaluated. RESULTS: Among 906 survey respondents
      (57% response rate), (median survival time: 7 years), "dry mouth" and "problems
      with my mucus" were reported moderate/severe (MDASI-HN item score >=5) in 39% and
      22% of respondents, while 14% reported moderate/severe "problems with teeth and
      gums". Smoking at the time of survey was significantly associated with the
      severity of oral symptoms including "mucus" (p = 0.03), "dry mouth" (p = 0.02),
      "problems with my teeth and gums" (p = 0.001). All the oral morbidities symptom
      items significantly, positively correlated with the mean interference scores
      reflecting adverse impact to quality of life (QOL): "mucus" (r = 0.445, p <
      0.001), "problems with teeth" (r = 0.446, p < 0.001), "mouth sores" (r = 0.321, p
      < 0.001) and "dry mouth" (r = 0.459, p < 0.001). CONCLUSION: This study showed
      that 45.5% reported at least one late oral morbidity at moderate/severe level
      which negatively correlated overall function, even years after treatment.

PMID- 30115483
TI  - ERK-TSC2 signalling in constitutively-active HRAS mutant HNSCC cells promotes
      resistance to PI3K inhibition.
AB  - OBJECTIVES: The PI3K/AKT/mTOR pathway is frequently altered in head and neck
      squamous cell cancer (HNSCC), making this pathway a logical therapeutic target.
      However, PI3K targeting is not universally effective. Biomarkers of response are
      needed to stratify patients likely to derive benefit and exclude those unlikely
      to respond. MATERIALS AND METHODS: We examined the sensitivity of cell lines with
      constitutively-active (G12V mutant) HRAS and wild-type HRAS to PI3K inhibition
      using flow cytometry and cell viability assays. We then overexpressed and
      silenced HRAS and measured sensitivity to the PI3K inhibitor BYL719.
      Immunoblotting was used to determine activation of the PI3K pathway. MEK and mTOR
      inhibitors were then tested in HRAS mutant cells to determine their efficacy.
      RESULTS: HRAS mutant cell lines were non-responsive to PI3K inhibition.
      Overexpression of HRAS led to reduced susceptibility to PI3K inhibition, while
      knockdown improved sensitivity. Immunoblotting revealed suppressed AKT
      phosphorylation upon PI3K inhibition in both wild-type and HRAS mutant cell
      lines, however mutant lines maintained phosphorylation of S6, downstream of mTOR.
      Targeting mTOR effectively reduced viability of HRAS mutant cells and we
      subsequently examined the ERK-TSC2-mTOR cascade as a mediator of resistance to
      PI3K inhibition. CONCLUSIONS: HRAS mutant cells are resistant to PI3K inhibition
      and our findings suggest the involvement of a signalling intersection of the MAPK
      and PI3K pathways at the level of ERK-TSC2, leading to persistent mTOR activity.
      mTOR inhibition alone or in combination with MAPK pathway inhibition may be a
      promising therapeutic strategy for this subset of HNSCC tumors.

PMID- 30115485
TI  - Pain relief during labour: challenging the use of intramuscular pethidine.

PMID- 30115484
TI  - Intravenous remifentanil patient-controlled analgesia versus intramuscular
      pethidine for pain relief in labour (RESPITE): an open-label, multicentre,
      randomised controlled trial.
AB  - BACKGROUND: About a third of women receiving pethidine for labour pain
      subsequently require an epidural, which provides effective pain relief but
      increases the risk of instrumental vaginal delivery. Remifentanil patient
      controlled analgesia (PCA) in labour is an alternative to pethidine, but is not
      widely used. We aimed to evaluate epidural analgesia progression among women
      using remifentanil PCA compared with pethidine. METHODS: We did an open-label,
      multicentre, randomised controlled trial in 14 UK maternity units. We included
      women aged 16 years or older, beyond 37 weeks' gestation, in labour with a
      singleton cephalic presentation, and who requested opioid pain relief. We
      randomly assigned eligible participants (1:1) to either the intravenous
      remifentanil PCA group (40 MUg bolus on demand with a 2 min lockout) or the
      intramuscular pethidine group (100 mg every 4 h, up to 400 mg in 24 h), using a
      web-based or telephone randomisation service with a minimisation algorithm for
      parity, maternal age, ethnicity, and mode of labour onset. Because of the
      differences in routes of drug administration, study participants and health-care
      providers were not masked to the group allocation. The primary outcome was the
      proportion of women who received epidural analgesia after enrolment for pain
      relief in labour. Primary analyses were unadjusted and analysed by the intention
      to-treat principle. This study is registered with the ISRCTN registry, number
      ISRCTN29654603. FINDINGS: Between May 13, 2014, and Sept 2, 2016, 201 women were
      randomly assigned to the remifentanil PCA group and 200 to the pethidine group.
      One participant in the pethidine group withdrew consent, leaving 199 for
      analyses. The proportions of epidural conversion were 19% (39 of 201) in the
      remifentanil PCA group and 41% (81 of 199) in the pethidine group (risk ratio
      0.48, 95% CI 0.34-0.66; p<0.0001). There were no serious adverse events or drug
      reactions directly attributable to either analgesic during the study.
      INTERPRETATION: Intravenous remifentanil PCA halved the proportion of epidural
      conversions compared with intramuscular pethidine. This finding challenges
      routine pethidine use as standard of care in labour. FUNDING: National Institute
      for Health Research Clinician Scientist Award.

PMID- 30115486
TI  - The survival after a radical hysterectomy for cervical cancer by open surgery is
      significantly better then after minimal invasive surgery: Evidence beats gut
      feeling!
AB  - Surgery is the golden standard for early stage cervical cancer. Surgery can be
      done by an open or a closed procedure. A closed procedure or minimal invasive
      surgery (MIS) reduces the morbidity and retrospective analysis suggested that
      there was no difference in survival. In daily practice this meant that open
      surgery was replaced by MIS. The results of the first randomized phase 3 trial
      comparing open versus closed surgery threw another light on the topic. This well
      designed RCT revealed that MIS was associated with significant higher recurrence
      rates and a significant worse overall survival. Changing from MIS to open surgery
      would reduce the number of recurrences by 6 and the number of deaths by 5 per
      100. The study has several strong points and some limitations. The quality of MIS
      is equal to that of open surgery if you look at the tissue specimens.
      Explanations has therefore to be sought in the differences between the surgical
      procedures. Research is needed to test these explanations and to look for other
      reasons. The RCT is convincing, but there is also need for caution. Since, it is
      still possible that some fine tuning of the initial data could modify the overall
      conclusion. The impact of the RCT in daily practice should not be underestimated.
      As clinicians we have to accept this level 1 evidence. During counselling we have
      to discuss with the patient that open surgery in early cervical cancer has a
      survival benefit at the cost of an increased short-term morbidity. The patient
      herself is the prime and only decision maker. The surgery should be tailored and
      performed according to the wishes of the patient. Whether this will change
      current practice has to be seen.

PMID- 30115487
TI  - Body fat, metabolic syndrome and hyperglycemia in South Asians.
AB  - The prevalence of overweight and obesity is escalating in South Asian countries.
      South Asians display higher total and abdominal obesity at a lower BMI when
      compared to Whites. Consequently, metabolic dysfunction leading to metabolic
      syndrome (MetS) and type 2 diabetes mellitus (T2DM) will account for a majority
      of the health burden of these countries. In this review, we discuss those factors
      that contribute to MetS and T2DM in South Asians when compared to whites,
      focusing on adiposity. Abdominal obesity is the single-most important risk factor
      for MetS and its predisposition to T2DM. Excessive ectopic fat deposition in the
      liver (non-alcoholic fatty liver disease) has been linked to insulin resistance
      in Asian Indians, while the effects of ectopic fat accumulation in pancreas and
      skeletal muscle need more investigation. South Asians also have lower skeletal
      muscle mass than Whites, and this may contribute to their higher risk T2DM.
      Lifestyle factors contributing to MetS and T2DM in South Asians include
      inadequate physical activity and high intakes of refined carbohydrates and
      saturated fats. These are reflective of the recent but rapid economic transition
      and urbanization of the South Asian region. There is need to further the research
      into genetic determinants of dysmetabolism as well as gene x environment
      interactions. Collectively, MetS and T2DM have multi-factorial antecedents in
      South Asians and efforts to combat it through low-cost and socio-culturally
      appropriate lifestyle interventions need to be supported.

PMID- 30115488
TI  - Letter to the editor: Sex and the eye test.

PMID- 30115489
TI  - Varied patterns of catch-up in child growth: Evidence from Young Lives.
AB  - The development of human capabilities for many disadvantaged children around the
      world depends on growth recovery ('catch-up growth'). Here we develop a novel
      framework that allows different types of catch-up growth to be classified and
      estimated. We distinguish between catch-up in the mean of a group toward that of
      a healthy reference population versus catch-up within the group. We show these
      different growth types can be tested in a unified setting using a latent growth
      framework. We apply the results to four developing countries, using longitudinal
      data on 7641 children collected over the period 2002-2013. The results show catch
      up growth rates are generally modest but vary significantly between countries,
      and that local environmental factors are material to variation in child growth
      trajectories. The paper discusses the benefits of the new framework versus
      current methods, shows that the method is feasible, and suggests they call for
      intervention designs that are sensitive to community and country contexts.

PMID- 30115490
TI  - Ultrasound-Guided Pharmacomechanical Thrombolysis and Angioplasty for Treatment
      of Acute Thrombotic Prosthetic Arteriovenous Access: 5-Year Experience with 154
      Procedures in a Single Center.
AB  - Pharmacomechanical thrombolysis (PMT) and percutaneous transluminal angioplasty
      (PTA) for the treatment of acute thrombotic prosthetic arteriovenous access
      (PAVA) are conventionally guided by radiography, which may cause radiation injury
      and requires the use of radiographic contrast media. The aim of the present study
      was to summarize our experience with ultrasound-guided PMT and PTA as an
      alternative to radiographic guidance. Between December 2012 and October 2016, 114
      patients with acute thrombosis of PAVA were treated urgently with ultrasound
      guided PMT and PTA to restore blood flow. The patients were followed up every 3
      mo postoperatively. The 114 included patients underwent 154 episodes of
      ultrasound-guided PMT and PTA and were followed up for a mean of 20.7 +/- 9.1 mo.
      The technical success rate was 91.6%, and the clinical success rate was 97.4%.
      Post-intervention-assisted primary patency rates at 3, 6, 12 and 24 mo were
      90.8%, 78.8%, 66.3% and 50.9%, respectively. Post-intervention secondary patency
      rates at 3, 6, 12 and 24 months were 96.3%, 94.5%, 90.6% and 85.4%, respectively.
      PMT and PTA for the treatment of PAVA were performed successfully under the
      guidance of ultrasound with a success rate similar to that under radiographic
      guidance, thus avoiding radiation injury and contrast medium use, although close
      surveillance and timely intervention are imperative to ensure long-term patency.

PMID- 30115491
TI  - Corrigendum to 'Photosensitized methyl paraben induces apoptosis via caspase
      dependent pathway under ambient UVB exposure in human skin cells' [Food Chem.
      Toxicol. 108 (2017) 171-185].

PMID- 30115492
TI  - A series of camptothecin prodrugs exhibit HDAC inhibition activity.
AB  - Camptothecin plays an important role in clinical cancer treatment, and its
      derivatives are a favorite of pharmaceutical chemists. Herein, we have designed a
      series of camptothecin prodrugs that exhibit histone deacetylase (HDAC)
      inhibition activity based on the synergy effect between HDAC inhibitors and
      camptothecin derivatives. With the evaluation of stability in buffers or plasma
      from human or mouse model, an appropriate linker was found, so the active drug
      can be released efficiently and compound 21a exhibited strong antiproliferative
      activity in A549 and HCT-116 cell lines. These results indicated that the well
      designed prodrug can be promising in cancer treatment.

PMID- 30115493
TI  - Design and synthesis of novel 6-hydroxy-4-methoxy-3-methylbenzofuran-7
      carboxamide derivatives as potent Mnks inhibitors by fragment-based drug design.
AB  - A novel series of 6-hydroxy-4-methoxy-3-methylbenzofuran-7-carboxamide
      derivatives featured with various C-2 substituents were designed and synthesized
      as Mnks inhibitors through fragment-based drug design. Among them, 5b, 5i, 5o and
      8k showed the best Mnk2 inhibitory activity with IC50 values of 1.45, 1.16, 3.55
      and 0.27 MUM, respectively. And these compounds inhibited the activity of Mnk1 at
      the same time. Furthermore, compounds 5o and 8k exhibited anti-proliferative
      effects to human leukemia cancer THP-1 and MOLM-13 cell lines and colon cancer
      HCT-116 cell line. Moreover, Western blot assay suggested that 8k could decrease
      the levels of p-eIF4E in a dose-dependent manner in HCT-116 cells. Docking
      studies demonstrated strong interactions between 8k and Mnk2. Therefore, this
      unique benzofuran scaffold demonstrated great potential to be further explored as
      potent Mnks inhibitors with improved potency.

PMID- 30115494
TI  - The effect of a multidisciplinary team on the implementation rates of major
      diagnostic and therapeutic procedures of chronic thromboembolic pulmonary
      hypertension.
AB  - BACKGROUND: Although guidelines have recommended that patients with chronic
      thromboembolic pulmonary hypertension (CTEPH) should be managed by a
      multidisciplinary team (MDT), there is a lack of clinical data indicating that
      the MDT improves CTEPH management. OBJECTIVES: The study aimed to identify the
      effect of an MDT on CTEPH management. METHODS: We divided the study period into
      pre-MDT and post-MDT eras and compared the implementation rates of major
      diagnostic and therapeutic procedures. RESULTS: Of 116 patients with CTEPH, 42
      (36.2%) were diagnosed in the post-MDT era. The implementation rates of right
      heart catheterization (10.8% vs. 97.6%, p < 0.001) and pulmonary endarterectomy
      (32.4% vs. 59.5%, p < 0.005) were significantly increased in the post-MDT era.
      Balloon pulmonary angioplasty was not performed in the pre-MDT era but was
      performed in the post-MDT era. CONCLUSIONS: The MDT appears to be associated with
      improved CTEPH management.

PMID- 30115495
TI  - Morton's ophthalmoscope.

PMID- 30115496
TI  - Acute macular neuroretinopathy: a case report.

PMID- 30115497
TI  - Proliferative diabetic retinopathy imaged by near-infrared reflectance.

PMID- 30115498
TI  - Corrigendum to "Incretin hormones receptor signaling plays the key role in
      antidiabetic potential of PTY-2 against STZ-induced pancreatitis" [Biomed.
      Pharmacother. 97 (330-338) 330-338].

PMID- 30115499
TI  - Selective Prefrontal Disinhibition in a Roving Auditory Oddball Paradigm Under N
      Methyl-D-Aspartate Receptor Blockade.
AB  - BACKGROUND: Disturbances in N-methyl-D-aspartate receptors (NMDARs)-as implicated
      in patients with schizophrenia-can cause regionally specific electrophysiological
      effects. Both animal models of NMDAR blockade and clinical studies in patients
      with schizophrenia have suggested that behavioral phenotypes are associated with
      reduction in inhibition within the frontal cortex. METHODS: Here we investigate
      event-related potentials to a roving auditory oddball paradigm under ketamine in
      healthy human volunteers (N= 18; double-blind, placebo-controlled, crossover
      design). Using recent advances in Bayesian modeling of group effects in dynamic
      causal modeling, we fit biophysically plausible network models of the auditory
      processing hierarchy to whole-scalp event-related potential recordings. This
      allowed us to identify regionally specific effects of ketamine in a distributed
      network of interacting cortical sources. RESULTS: We show that the effect of
      ketamine is best explained as a selective change in intrinsic inhibition, with a
      pronounced ketamine-induced reduction of inhibitory interneuron connectivity in
      frontal sources, compared with temporal sources. Simulations of these changes in
      an integrated microcircuit model shows that they are associated with a reduction
      in superficial pyramidal cell activity that can explain drug effects observed in
      the event-related potential. CONCLUSIONS: These results are consistent with
      findings from invasive recordings in animal models exposed to NMDAR blockers, and
      provide evidence that inhibitory interneuron-specific NMDAR dysfunction may be
      sufficient to explain electrophysiological abnormalities induced by NMDAR
      blockade in human subjects.

PMID- 30115500
TI  - Prognostic indicators lose their value with repeated resection of colorectal
      liver metastases.
AB  - BACKGROUND: The liver is the most common site of colorectal liver metastases
      (CRLM) and surgical resection improves overall survival in selected patients.
      Here, we investigate outcomes and relevant prognostic factors after repeated
      hepatic resections for CRLM. METHODS: From a prospective database, 578 patients
      who underwent 788 resections of colorectal liver metastases were included into
      this study. In total, 169 patients underwent a second and 41 patients had a third
      operation due to intrahepatic metastatic recurrence. Univariate and multivariate
      analyses were performed to determine prognostic risk factors. RESULTS: 5-year
      overall survival was 36.7% (95% CI: 30.2%; 43.2%) and 10-year survival was 20.3%
      (95% CI: 7.6%; 33.0%) in patients undergoing single resection. In patients
      undergoing a second or third resection, 5- and 10-year survival rates were 56.6%
      (95% CI: 45.0%; 68.2%) and 21.9% (95% CI: 6.8%; 37.0%) or 53.2% (95% CI: 32.4%;
      74.0%) and 25.4%, respectively. In patients undergoing single resection,
      established markers (number, size and pattern of CRLM [p = 0.030/0.015/<0.001], R
      status [p = 0.001], surgical/medical complications [p = 0.001/0.008], CEA-level
      [p = 0.001] and Fong-Score [p = 0.02]) were significantly associated with
      survival. In patients undergoing three resections, the only predictive markers
      were pT-stage of the primary tumor in univariate analysis (p = 0.013) and
      metachronous metastasis and medical complications in multivariate analysis (p =
      0.001/0.025). The Fong-Score had no predictive value in patients undergoing two
      (p = 0.08) or three (p = 0.7) resections. CONCLUSION: Established prognostic
      indicators are not applicable in patients undergoing repeated CRLM resection. In
      a highly-selected group of patients, repeated hepatic resections can be performed
      safely with favorable long-term outcomes.

PMID- 30115501
TI  - Zinc overload mediated by zinc oxide nanoparticles as innovative anti-tumor
      agent.
AB  - The predicted global cancer burden is expected to surpass 20 million new cancer
      cases by 2025. Despite recent advancement in tumor therapy, a successful cancer
      treatment remains challenging. The emerging field of nanotechnology offers great
      opportunities for diagnosis, imaging, as well as treatment of cancer. Zinc oxide
      nanoparticles (ZnO NP) were shown to exert selective cytotoxicity against tumor
      cells via a yet unknown mechanism, most likely involving the generation of
      reactive oxygen species (ROS). These nanoparticles are a promising therapeutic
      opportunity as zinc is a nontoxic trace element and its application in medically
      related products is considered to be safe. We could show that ZnO NP can exert
      cytotoxic effects on several human tumor cell lines. There can be found ZnO NP
      concentrations which selectively damage tumor cells while human fibroblasts do
      not sustain lasting damage. Cytotoxicity is attributable to the release of zinc
      ions from the nanoparticles outside the cells as well as to a direct cell
      nanoparticle interaction. This involves uptake of the particles into the tumor
      cells. With a silica shell the cytotoxicity can be delayed which can help in the
      future for a safe transport in the blood stream. Cellular damage finally
      cumulates in apoptotic cell death via zinc overload within 48 h after treatment
      with ZnO NP. A therapeutical perspective could be the targeted accumulation of
      ZnO NP at the tumor side to induce local zinc overload that substantially damages
      the tumor cells with no or low side effects. We suggest further studies to
      explore the potential of ZnO NP as an innovative anti-tumor agent.

PMID- 30115502
TI  - Case report: serratus intercostal plane block/BRILMA and sedation for mastectomy
      in a high risk patient.
AB  - Breast cancer surgery can benefit from regional anaesthesia techniques, which can
      be used as a sole anaesthetic procedure in some cases where risk for general
      anaesthesia is high. Regional anaesthesia allows early recovery, reduces
      postoperative opioid and non opioid analgesics consumption and helps early home
      discharge, reducing thus costs. We present a case of an 87-year-old woman with
      multiple comorbidities who underwent breast cancer surgery. The patient was
      successfully surgically treated under serratus intercostal plane block
      anaesthesia. We discuss the use and benefits of the serratus intercostal plane
      block in thoracic procedures.

PMID- 30115503
TI  - GLUT-1 deficiency presenting with seizures and reversible leukoencephalopathy on
      MRI imaging.
AB  - Glucose transporter type 1 (GLUT1) deficiency syndrome is a well recognised
      genetic neurometabolic disorder typically presenting with progressive
      encephalopathy, acquired microcephaly and drug-resistant epilepsy. Imaging is
      normal in the majority. Here we describe a 5-month-old boy who presented with
      motor delay, myoclonic jerks and tonic-clonic seizures. His MRI brain scan
      revealed confluent symmetrical T2 hyperintense signal abnormality in both
      anterior frontal lobes and delayed myelination. Neurometabolic screen revealed
      low CSF glucose and lactate levels. A pathogenic de novo heterozygous mutation in
      SLC2A1 (c.275+1G > A) confirmed the diagnosis of GLUT1 deficiency. Ketogenic diet
      resulted in a dramatic termination of his seizures at 72 h. At 15 months, he
      continued to be seizure free with marked developmental catch up. Repeat imaging
      revealed a significant resolution of the previously seen changes. This case
      suggests that GLUT1 deficiency should be considered in the differential diagnosis
      of infants with suspected genetic leukoencephalopathies with important treatment
      implications.

PMID- 30115504
TI  - Concussion incidence in amateur Australian Rules Footballers.
AB  - Australian Rules Football is a collision sport that is associated with increased
      sport-related concussion risk. Sport-related concussion is a common form of mild
      traumatic brain injury that is now recognised as a serious health issue. This
      study measured the concussion incidence rate for amateur Australian Rules players
      over 3 seasons (2015-2017) by athlete exposures-a metric used widely in the
      literature. This study also reported concussion incidence based on player match
      hours, a less common yet more accurate method of reporting concussion incidence
      which takes match duration into account. Accurate concussion incidence reporting
      in amateur Australian Rules Football quantifies the problem of concussion in this
      sport. This may be necessary to inform players of their concussion injury risk
      and to help guide rule changes to protect players from this injury.

PMID- 30115505
TI  - High Density of Periaortic Adipose Tissue in Abdominal Aortic Aneurysm.
AB  - OBJECTIVES: Perivascular adipose tissue (PVAT) is currently seen as a paracrine
      organ that produces vasoactive substances, including inflammatory agents, which
      may have an impact on the vasculature. In this study PVAT density was quantified
      in patients with an aortic aneurysm and compared with those with a non-dilated
      aorta. Since chronic inflammation, as the pathway to medial thinning, is a
      hallmark of abdominal aortic aneurysms (AAAs), it was hypothesised that PVAT
      density is higher in AAA patients. METHODS: In this multicentre retrospective
      case control study, three groups of patients were included: non-treated
      asymptomatic AAA (n = 140), aortoiliac occlusive disease (AIOD) (n = 104), and
      individuals without aortic pathology (n = 97). A Hounsfield units based analysis
      was performed by computed tomography (CT). As a proxy for PVAT, the density of
      adipose tissue 10 mm circumferential to the infrarenal aorta was analysed in each
      consecutive CT slice. Intra-individual PVAT differences were reported as the
      difference in PVAT density between the region of the maximum AAA diameter (or the
      mid-aortic region in patients with AIOD or controls) and the two uppermost slices
      of infrarenal non-dilated aorta just below the renal arteries. Furthermore,
      subcutaneous (SAT) and visceral (VAT) adipose tissue measurements were performed.
      Linear models were fitted to assess the association between the study groups,
      different adipose tissue compartments, and between adipose tissue compartments
      and aortic dimensions. RESULTS: AAA patients presented higher intra-individual
      PVAT differences, with higher PVAT density around the aneurysm sac than the
      healthy neck. This association persisted after adjustment for cardiovascular risk
      factors and diseases and other fat compartments (beta = 13.175, SE 4.732, p =
      .006). Furthermore, intra-individual PVAT differences presented the highest
      correlation with aortic volume that persisted after adjustment for other fat
      compartments, body mass index, sex, and age (beta = 0.566, 0.200, p = .005).
      CONCLUSION: The results suggest a relation between the deposition of PVAT and AAA
      pathophysiology. Further research should explore the exact underlying processes.

PMID- 30115506
TI  - Experiences With Querying Gender Identity Across Seven Adolescent Medicine Sites.
AB  - PURPOSE: To determine how the seven Maternal and Child Health Bureau funded
      Leadership and Education in Adolescent Health (LEAH) programs currently obtain
      information on gender identity from their patients. METHODS: A computerized
      survey was sent to all LEAH site directors with questions to identify if and how
      programs documented youth's gender identity and barriers to implementation.
      RESULTS: With response rate of 100%, seven LEAH programs reported a total of 43
      primary care and specialty clinics. For clinics with Electronic Health Records,
      67% of clinics had a standardized gender identity question. Barriers to
      implementing a standardized question included concerns about confidentiality,
      lack of trained providers, low numbers of transgender patients, and no validated
      gender identity question. CONCLUSIONS: Incorporation of inquiry of gender
      identity is possible in numerous clinical settings that serve adolescents. Future
      research is needed to determine how this information affects conversations with
      providers and necessary referrals to treatment.

PMID- 30115507
TI  - Young Adults' Access to Insurance Through Parents: Relationship to Receipt of
      Reproductive Health Services and Chlamydia Testing, 2007-2014.
AB  - PURPOSE: Adolescents' concerns about confidential service receipt have been
      linked to avoidance of sexual and reproductive healthcare. Healthcare system
      changes allowing young adults to remain on a parent's health insurance plan up to
      age 26 may have extended these concerns to young adults. This study examines: (1)
      The association between the relationship of young women to primary health plan
      policy holder (parent or self) on receipt of reproductive health services and
      chlamydia screening. (2)Changes, over time, in the proportion of young women who
      are parentally- versus self-insured. METHODS: Cross-sectional analysis of
      commercially insured young women (18-25) enrolled >=330days in health plans
      included in the Truven Health MarketScan commercial claims and encounters
      database (2007-2014). RESULTS: Between 2010 and 2014, the proportion of
      parentally-insured young women increased significantly across all age groups (AOR
      = 4.32, CI = 4.29, 4.33). Compared to self-insured young women, parentally
      insured young women were less likely to receive a reproductive health service
      (AOR = .66, CI = .66, .67) and sexually active parentally-insured young women
      were less likely to receive chlamydia testing (AOR = .75, CI = .75, .76) using
      their parent's insurance. CONCLUSIONS: Young women who are insured through a
      parent are less likely to receive reproductive health services or chlamydia
      testing using their parent's insurance, which could suggest that concerns about
      confidential receipt of health services may result in missed care. Various
      policies, including those related to explanation of benefits sent to a plan
      policy holder outlining services received, may affect the receipt of confidential
      healthcare by young adults.

PMID- 30115508
TI  - Polytobacco Use Among a Nationally Representative Sample of Adolescent and Young
      Adult E-Cigarette Users.
AB  - PURPOSE: Electronic nicotine delivery systems (ENDS) are adolescents' most
      commonly used tobacco product and young adults' second most used. Little is known
      about ENDS use alongside other tobacco products (polytobacco use) and whether
      exclusive ENDS users differ from polytobacco ENDS users. METHODS: In spring 2016,
      we surveyed a nationally representative sample of 3,517 13-25-year olds (36.9% 13
      17-year olds), and examined sociodemographic and relative risk perceptions
      between two groups of past 30-day ENDS users: exclusive (only ENDS) and
      polytobacco (ENDS and at least one other tobacco product). RESULTS: 4.5% of
      adolescents and 10% of young adults reported past 30-day ENDS use (n = 281;
      analytic sample). ENDS users were 38.8% female and 70.6% white. Over half (55.9%)
      were polytobacco ENDS users. The most common patterns of polytobacco ENDS use
      were ENDS and cigarettes (11.5%), ENDS and cigars (7.7%), and ENDS, cigars, and
      waterpipe (5.2%). Those who perceived ENDS to be less harmful than cigarettes
      were more likely to be exclusive ENDS users than those who perceived ENDS to be
      as or more harmful than cigarettes (adjusted odds ratio = 2.6, confidence
      interval = 1.2, 5.7). There were no differences between ENDS groups on age, race,
      sex, parental education, sexual orientation, or ENDS use frequency. CONCLUSIONS:
      Just over half of ENDS users also used other tobacco products, increasing their
      risk for nicotine addiction and other health harms. The Food and Drug
      Administration is responsible for communicating product risk to consumers and
      should consider common patterns of use and relative risk perceptions in its ENDS
      public education efforts.

PMID- 30115509
TI  - The relationship between trust in primary care physicians and medication
      knowledge among diabetic patients.
AB  - BACKGROUND: Patients' trust in their physicians is critical to ensuring quality
      in healthcare. Despite the fact that both medication knowledge and trust in
      healthcare providers positively correlate with improved clinical outcomes, the
      presence of a link between these two attributes remains to be established.
      OBJECTIVES: To determine whether a relationship exists between patients' trust in
      their primary care physicians and their medication knowledge. METHODS: Patient
      trust was measured using the healthcare relationship (HCR) trust scale, and the
      medication knowledge by the self-reported medication knowledge questionnaire.
      Both forms were translated into Arabic by bilingual healthcare professionals. The
      relationship between the self-reported medication knowledge questionnaire scores
      and HCR-trust scale scores was determined by multiple linear regression,
      controlling for confounding variables. RESULTS: Based on information collected
      from 293 diabetic patients, a positive relationship was identified between
      patients' knowledge of medications and their trust in primary care physicians
      (beta = 0.115; 95% confidence interval, 0.076-0.153; p < 0.0001). Medication
      knowledge was also positively associated with the female sex and education.
      CONCLUSION: A significant relationship exists between the patients' knowledge of
      their prescription medications and trust placed in their primary care physicians.
      The underlying mechanism of this association warrants further studies.

PMID- 30115510
TI  - Understanding the process of clinical judgement for pharmacists when making
      clinical decisions.
AB  - Clinical decision-making is arguably the most important and underappreciated
      skill in pharmacy. It can be described as four discrete steps: information
      gathering, clinical reasoning and judgement and, the decision process. The
      information gathering and decision negotiation steps and to some extent clinical
      reasoning are addressed either implicitly or explicitly by practitioners and
      educators. Clinical judgement, however, remains a largely unexplored concept for
      clinical decision-making in healthcare therapeutics. It defines how practitioners
      arrive at a favourable treatment strategy and, due to the often complicated
      benefit:risk evaluations, is often linked with concepts relating to ambiguity. In
      this article, we use game theory to explore the judgement stage of clinical
      decision-making. Game theory allows us to provide a quantitative evaluation of
      clinical judgement and explore concepts such as ambiguity and its sources in
      healthcare. Clarifying the elements involved in the judgement stage of clinical
      decision-making will enable a better understanding of how pharmacists contribute
      patient care in healthcare teams.

PMID- 30115511
TI  - Amelioration of mechanism-based inactivation of CYP3A4 by a H-PGDS inhibitor.
AB  - This work describes the rational amelioration of mechanism-based inactivation
      (MBI) of Cytochrome P450 (CYP) 3A4 in a human hematopoietic prostaglandin D
      synthase (hH-PGDS) inhibitor (cpd 1). We utilized metabolism reports in order to
      check if patterns in the metabolism of 1 and similar compounds by CYP3A4 could be
      deciphered. Then we used structure based design, first modifying the CYP3A4
      crystal structure (pdb code: 4NY4) by adding an oxyferryl moiety to the heme,
      followed by validating the modified structure to obtain the 1' and 4 position
      oxidation products of midazolam and then recapitulating the metabolism patterns
      deciphered previously for 1 and analogs. We checked if the pattern deciphered
      could lead to a putative reactive moiety. Finally we used the docking pose of 1
      into this model of the modified CYP3A4 crystal structure to guide transformation
      of 1 into MBI-free H-PGDS inhibitors.

PMID- 30115512
TI  - Development of a translational medicine protocol for an NCTN genitourinary
      clinical trial: Critical steps, common pitfalls and a basic guide to
      translational clinical research.
AB  - Translational medicine (TM) components of prospective clinical trials provide an
      invaluable opportunity to test hypotheses that contribute to our knowledge of
      human disease biology and/or the mechanism of action of a given therapeutic
      intervention. Our ability to sample tumors and their microenvironment, and the
      depth and breadth of biological information that can be extracted from them, has
      increased exponentially in recent years. This information is critical to guide
      the next steps clinical research if we are to accelerate the pace of progress in
      cancer treatment. Thus, TM studies should be considered key components of any
      clinical trial. However, TM studies are costly and biologic sampling can impose
      significant morbidity on our patients. Therefore, TM investigators should be
      engaged early in the design process (similar to a statistician) to ensure that
      the most imperative research questions are rigourosly defined, that the obtained
      specimens can be used to answer them and that the results will serve as the
      foundation for additional studies. In this review, we focus on TM studies in the
      context of the National Cancer Institute's National Clinical Trials Network
      trials and offer a description of the genesis of TM components, methods in sample
      acquisition and biomarker research, and a guide to funding mechanisms, in order
      to provide a blueprint for future TM research protocols. While TM studies can
      take many forms, the research discussed primarily focusses on basic and
      translational research involving molecular, cellular, and immunobiology.

PMID- 30115513
TI  - Survey on changes in subjective symptoms, onset/trigger factors, allergic
      diseases, and chemical exposures in the past decade of Japanese patients with
      multiple chemical sensitivity.
AB  - BACKGROUND: Recently, with rapid changes in the Japanese lifestyle, the clinical
      condition of patients with multiple chemical sensitivity (MCS) may also have
      undergone change. Thus, we conducted a new survey for subjective symptoms,
      ongoing chemical exposures, the prevalence of allergic diseases, and presumed
      onset/trigger factors in patients with MCS and compared results with those of an
      old survey from ten years ago. METHODS: The new survey was conducted from 2012 to
      2015 and the old survey was independently conducted from 1999 to 2003, meaning it
      was not a follow-up study. Patients were initially diagnosed by physicians at
      five medical institutions with MCS specialty outpatient services, with 111 and
      103 patients participating in the new and old surveys, respectively. The controls
      were a general population living in Japan, with 1313 and 2382 participants in the
      new and old surveys, respectively. Subjective symptoms and ongoing chemical
      exposure were evaluated using a quick environmental exposure sensitivity
      inventory. Additionally, from clinical findings recorded by an attending
      physician, the prevalence of allergic diseases and presumed onset/trigger factors
      were evaluated. Differences between new and old surveys were analyzed using
      logistic regression analyses and significance tests. RESULTS: Compared with ten
      years ago: (1) Regarding factors affecting patients with ongoing chemical
      exposures, the proportion of patients affected decreased significantly for two
      items only (insecticides and second-hand smoke). The proportion of controls
      showing ongoing exposure to 8 out of 10 items changed significantly. (2) In
      patients, scores for chemical intolerances, other intolerances, and life impacts
      increased significantly. (3) In terms of the prevalence of allergic diseases
      among patients with MCS, bronchial asthma (adjusted odds ratio [AOR]: 5.19),
      atopic dermatitis (AOR: 3.77), allergic rhinitis (AOR: 5.34), and food allergies
      (AOR: 2.63) increased significantly, while hay fever (AOR: 0.38) and drug
      allergies (AOR: 0.40) decreased significantly. (4) With regard to construction
      and renovation, which was the presumed predominant onset/trigger factor for MCS
      10 years ago, this decreased from 68.9% to 35.1%; in contrast, electromagnetic
      fields (0.0%-26.1%), perfume (0.0%-20.7%), and medical treatment (1.9%-7.2%)
      increased significantly, confirming the diversification of onset/trigger factors.
      CONCLUSION: Compared to ten years ago, for patients with MCS, an increase in
      avoidance behavior toward chemical substance exposures, which were presumed to be
      aggravating factors for symptoms, was confirmed. It has been suggested that the
      ongoing chemical exposure of the general population in Japan has largely changed.
      In addition, for patients with MCS, chemical intolerances and life impacts have
      become severe, the prevalence of the main allergic diseases has increased, and
      onset/trigger factors have become diversified.

PMID- 30115514
TI  - Tracheobronchial Foreign Body in Small Children: The Combination of Flexible
      Bronchoscopy and the Urology Stone Retrieval Basket.

PMID- 30115515
TI  - Causes and outcomes in studies of fear of childbirth: A systematic review.
AB  - PROBLEM: Fear of childbirth negatively affects women during pregnancy and after
      birth. AIM: To summarise the findings of published studies regarding possible
      causes/predisposing factors and outcomes of fear of childbirth for childbearing
      women. DESIGN: A systematic review, searching five databases in March 2015 for
      studies on causes/predisposing factors and outcomes of fear of childbirth, as
      measured during pregnancy and postpartum. Quality of included studies was
      assessed independently by pairs of authors. Data were extracted independently by
      reviewer pairs and described in a narrative analysis. FINDINGS: Cross-sectional,
      register-based and case-control studies were included (n=21). Causes were grouped
      into population characteristics, mood-related aspects, and pregnancy and birth
      related aspects. Outcomes were defined as mood-related or pregnancy and birth
      related aspects. Differing definitions of fear of childbirth were found and meta
      analysis could only be performed on parity, in a few studies. CONCLUSIONS:
      Stress, anxiety, depression and lack of social support are associated with fear
      during pregnancy. Need for psychiatric care and presence of traumatic stress
      symptoms are reported outcomes together with prolonged labour, longer labours,
      use of epidural and obstetric complications. Nulliparous and parous women have
      similar levels of fear but for different reasons. Since the strongest predictor
      for fear in parous women is a previous negative birth experience or operative
      birth, we suggest it is important to distinguish between fear of childbirth and
      fear after birth. Findings demonstrate the need for creating woman-centred
      birthing environments where women can feel free and secure with low risk of
      negative or traumatic birth experiences and consequent fear.

PMID- 30115516
TI  - Impact of body composition on survival and morbidity after liver resection in
      hepatocellular carcinoma patients.
AB  - BACKGROUND: Hepatocellular carcinoma is the most common innate liver tumor. Due
      to improved surgical techniques, even extended resections are feasible, and more
      patients can be treated with curative intent. As the liver is the central
      metabolic organ, preoperative metabolic assessment is crucial for risk
      stratification. Sarcopenia, obesity and sarcopenic obesity characterize body
      composition and metabolic status. Here we present the impact of body composition
      on survival after liver resection in patients with hepatocellular carcinoma.
      METHODS: A retrospective database analysis of 70 patients who were assigned for
      liver resection due to hepatocellular carcinoma was conducted. For assessment of
      sarcopenia and obesity, skeletal muscle surface area was measured at lumbar
      vertebra 3 level (L3) in preoperative four-phase contrast enhanced abdominal CT
      scans, and L3 muscle index and body fat percentage were calculated. RESULTS:
      Univariate analysis comparing the survival curves using the score test
      demonstrated superior postoperative overall survival for sarcopenic (P = 0.035)
      and sarcopenic obese (P = 0.048) patients as well as a trend favoring obese (P =
      0.130) subjects. Whereas multivariate analysis could not identify significant
      difference in postoperative survival regarding sarcopenia, obesity or sarcopenic
      obesity. Only large tumor size, multifocal disease and male gender were risk
      factors for long-term survival. CONCLUSIONS: Sarcopenia, obesity and sarcopenic
      obesity are indeed no risk factors for poor postoperative survival in this study.
      Our data do not support the evaluation of sarcopenia, obesity and sarcopenic
      obesity before liver resection in hepatocellular carcinoma patients.

PMID- 30115517
TI  - Multicenter International Survey on the Clinical Practice of Ultra-Fast-Track
      Anesthesia with On-Table Extubation in Pediatric Congenital Cardiac Surgery.
AB  - OBJECTIVE: To describe global practices for on-table extubation (OTE) in
      pediatric cardiac anesthesia in European and non-European countries. DESIGN:
      Multiple-choice, web-based survey with 34 questions addressing organizational
      data, existence of OTE programs, inclusion and exclusion criteria for OTE, and
      intraoperative and immediate postoperative management. SETTING: Online survey
      endorsed by the European Association of Cardiothoracic Anesthesiologists.
      PARTICIPANTS: Anesthesiologists departments in European and non-European
      pediatric cardiac surgical centers. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: The survey was sent to 144 pediatric cardiac surgical centers in 29
      countries as a web-based questionnaire. Addressees were pediatric cardiac
      anesthesiologists who were members of European Association of Cardiothoracic
      Anesthesiologists or were known to the authors. The response rate was 63%. Fifty
      percent of the respondents were practicing in university hospitals. The survey
      demonstrated that 76% of the respondents practiced OTE, with 50% of the pediatric
      cardiac anesthesiologists regularly performing OTE in different proportions,
      ranging from 1 to 51% of on-pump pediatric cardiac surgeries. Seventy-seven
      percent of respondents made their decision to perform OTE on an individual case
      by-case basis. Seventy-eight percent of the congenital cardiac lesions deemed
      eligible for OTE fell into Risk Adjustment for Congenital Heart Surgery-1
      categories 1 and 2. In patients for whom OTE was planned, anesthesia primarily
      was maintained using a combined inhalational and intravenous technique. The main
      reasons not to perform OTE were that it was deemed to provide no major advantage
      (45%), to be dangerous (9%), or to decrease operating room efficiency by
      increasing operating room turnover time (36%). CONCLUSION: The survey
      demonstrated that the majority of the approached pediatric cardiac
      anesthesiologists practice OTE regularly in pediatric cardiac surgery. Frequency
      of OTE and inclusion criteria vary widely. The observations made in this survey
      should prompt appropriately powered, randomized controlled clinical trials to
      examine the effect of OTE on various effectiveness and safety outcomes.

PMID- 30115518
TI  - Houston, ECMO Has Landed.

PMID- 30115519
TI  - Bioelectrical Impedance Phase Angle-Predictor of Blood Transfusion in Cardiac
      Surgery.
AB  - OBJECTIVE: To determine whether bioelectrical impedance-derived phase angle (PA)
      can be a predictor of red blood cell (RBC) transfusion in patients undergoing
      cardiac surgery. DESIGN: An observational retrospective study of prospectively
      collected data. SETTING: Single center, tertiary referral university hospital.
      PARTICIPANTS: The study sample comprised 642 adult patients undergoing elective
      cardiac surgery. INTERVENTIONS: Patient demographic and clinical variables were
      collected. The body composition of the patients was evaluated by bioelectrical
      impedance analysis (BIA) the day prior to surgery. The rates of postoperative RBC
      transfusion were recorded. MEASUREMENTS AND MAIN RESULTS: Among the 642 patients
      (67.8% men, median age of 66 [range 59-73]) included in the present study, 210
      (32.7%) received at least 1 RBC unit postoperatively. Hypertension, preoperative
      stroke, renal failure, preoperative hemoglobin and hematocrit values, BIA-derived
      PA, aortic crossclamp time, and cardiopulmonary bypass (CPB) time were associated
      with the risk of RBC transfusion in the univariate analysis, and were included in
      the final multivariate regression model. Preoperative stroke (odds ratio [OR]
      0.394; 95% confidence interval [CI]: 0.183-0.848; p = 0.017), preoperative
      hemoglobin values (OR 0.943; 95% CI: 0.928-0.960; p < 0.001), PA <15th percentile
      (OR 2.326; 95% CI: 1.351-4.000; p = 0.002), and CPB time (OR 1.013; 95% CI: 1.008
      1.018; p < 0.001) were identified as independent predictors of RBC transfusion.
      CONCLUSION: Several factors were identified to be associated significantly with
      postoperative RBC transfusion in patients undergoing cardiac surgery. Among the
      conventional predictors, the value of the BIA-derived PA was indicated as a
      potent prognostic tool.

PMID- 30115520
TI  - Determination of the activity and relative abundance of mRNA for antioxidant
      enzymes in stallion testicular and epididymal tissues: A comparison between two
      breeding seasons.
AB  - The key prerequisite for successful insemination is sperm characterized to have
      positive values for morphological and biological variables which are determined
      by, among others, effective antioxidant protection during the lifespan of sperm
      cells. This study evaluated the activity and relative abundance of mRNA for
      antioxidant enzymes in stallion testicular and epididymal tissues during breeding
      (n = 5) and non-breeding (n = 5) seasons. The activity of superoxide dismutase
      (SOD) was greater (P < 0.05) during the breeding season, in particular in the
      testes and the caput epididymis, and SOD1 was the predominant isoform of the
      enzyme. The expression of the SOD3 gene was markedly less in the analyzed
      tissues, which indicates that this enzyme contributes to the antioxidant
      protection of the stallion reproductive tract. The activity of catalase (CAT) was
      less (P < 0.05) in the testes during both seasons while its relative abundances
      only during the breeding season. The greatest CAT activity was noted in the cauda
      epididymis during the breeding season. The activity of glutathione peroxidases
      (GPx) was greater (P < 0.05) in the testes than in other tissues and 10-fold
      greater during the breeding season. Similarly, relative abundance of GPx5 mRNA
      was greater (P < 0.05) in the caput epididymis than in the remaining tissues
      during both seasons. This study demonstrated that season has an ambiguous
      influence on the antioxidant defense system in stallion reproductive tissues.
      Seasonal differences in the present study, however, indicate that the
      reproductive system of stallions adapts well to environmental seasonal changes.

PMID- 30115521
TI  - Noble scallop, Chlamys nobilis, sperm motility duration in the post-activation
      phase.
AB  - Sperm motility in the post-activation phase is important for conducting and
      assessing species-specific artificial fertilization protocols. This study
      characterizes spermatozoa movement of the noble scallop, Chlamys nobilis, during
      the post-activation phase. Sperm samples were diluted and activated by fresh
      seawater, and subsequently incubated at 26  degrees C for 4 h. Sperm movement
      variables including total motile sperm (TM), rapid sperm (RAP), curvilinear
      velocity (VCL), straight-line velocity (VSL), average path velocity (VAP),
      lateral head displacement (ALH) and beat-cross frequency (BCF) after sperm
      activation was recorded and analyzed using the computer assisted semen analyze
      system. Based on the motility index (MI), the sperm movement was categorized into
      four groupings (twitching before full activation, full activation, twitching
      after full activation, and decreasing during the latter portion of the sperm
      motility pattern). The full activation lasted 21 min with the greatest movement
      characteristics except BCF, and there was no difference with twitching before
      full activation except for the RAP. The greatest TM was observed at 24.5 min
      after activation. The RAP, VCL, VSL, VAP and ALH values in the post-activation
      phase increased at full activation, followed by a subsequent decrease, while the
      BCF continued to trend downward throughout the study. This study contributes to
      the understanding on the sperm property of the noble scallop for gamete
      management, fertilization and spat production in aquaculture.

PMID- 30115522
TI  - Maternal dietary supplementation of arginine increases the ratio of total cloned
      piglets born to total transferred cloned embryos by improving the pregnancy rate
      of recipient sows.
AB  - The extremely low full-term developmental efficiency of cloned pig embryos limits
      the practical application of pig cloning techniques. Maternal dietary
      supplementation of the nutritionally important amino acid, arginine, can enhance
      prenatal developmental rate of in vivo fertilization-derived pig embryos. It was
      hypothesized that maternal dietary addition of arginine can also improve the
      developmental capacity of cloned pig embryos. To test this hypothesis, there was
      a comparison of the reproductive performance between recipient sows fed an L
      arginine-supplemented diet (L-Arg group) and those fed the control diet (control
      group). There was a subsequent comparison of the developmental indexes of cloned
      piglets farrowed in the L-Arg and control groups of surrogate sows. Dietary
      supplementation of L-arginine during gestation days 14-75 increased the plasma
      concentrations of arginine and arginine metabolites, including nitric oxide,
      spermidine, and putrescine in recipient sows of transferred cloned pig embryos.
      Although maternal arginine addition did not affect the birth weight and placental
      development indexes of newborn cloned piglets, it significantly increased the
      ratio of total cloned piglets born to total transferred cloned pig embryos by
      increasing the pregnancy rate of recipient sows. The results of this study
      suggest that nutritional management of recipient sows is an effective approach to
      improve the developmental rate of cloned pig embryos.

PMID- 30115525
TI  - Roles of insulin resistance and beta cell dysfunction in macrosomia among Chinese
      women with gestational diabetes mellitus.
AB  - AIMS: The aim was to examine associations of insulin resistance and beta cell
      dysfunction with macrosomia in Chinese women with gestational diabetes mellitus
      (GDM). METHODS: We performed a secondary analysis of 923 women with GDM enrolled
      in a randomized controlled trial in 2010-2012 in Tianjin, China. Insulin
      resistance and beta-cell function were estimated using Homeostasis model
      assessment. Binary logistic regression was used to obtain adjusted odds ratios
      (ORs) and 95% confidence intervals (CIs). A two-step adjustment scheme was used
      to control for effects of potential confounders. RESULTS: A total of 138 women
      (16.5%) had excessive weight gain, 127 (7.3%) had macrosomia and 150 (16.3%) had
      a large for gestational age (LGA) infant. Compared to women in bottom tertile of
      insulin resistance, women in upper tertile had increased risk of excessive weight
      gain (OR: 4.32, 95%CI: 1.95-9.62), macrosomia and LGA (OR: 2.61, 95%CI: 1.20
      5.69; 2.75, 95%CI: 1.35-5.62, respectively). The observed overall effects were
      mainly due to their large effect sizes among women with normal pre-pregnancy body
      weight. However, beta cell function was not found to be associated with either of
      them. CONCLUSIONS: Increased insulin resistance during pregnancy was associated
      with excessive weight gain, macrosomia and LGA in Chinese women with GDM.

PMID- 30115524
TI  - The association of adverse events with bivalent human papilloma virus
      vaccination: A nationwide register-based cohort study in Finland.
AB  - BACKGROUND: A bivalent HPV vaccine (Cervarix(r); HPV2, GlaxoSmithKline) was
      introduced into the Finnish national vaccination programme (NVP) in November 2013
      for girls aged 11-13 years with a catch-up for 14-15 year-olds. We evaluated the
      association between HPV2 and selected autoimmune diseases and clinical syndromes
      by conducting a nation-wide retrospective register-based cohort study. METHODS:
      First life-time occurrences of the relevant ICD-10 codes in girls aged 11-15
      years between Nov-2013 and Dec-2016 were obtained from the national hospital
      discharge register. Population denominators were obtained from the Population
      Information System and vaccination records from the National Vaccination
      Register. Registers were linked using unique personal identity codes. Association
      between HPV2 and 38 selected outcomes were studied using Cox regression, with age
      as the main time-scale and the first vaccination dose as the time-dependent
      exposure. The hazard ratios (HR) with 95%CI were assessed according to the time
      since exposure (entire follow-up, 0-180/181-365/>365 days). RESULTS: Of 240 605
      girls eligible for HPV2 vaccination, 134 615 (56%) were vaccinated. After
      adjustment for geographical area (6 hospital districts), country of origin
      (Finnish-born/not) and number of hospital contacts from 9 through 10 years of
      age, HRs ranged from 0.34 (95%CI 0.11-1.05) to 8.37 (95%CI 0.85-82.54) and HPV2
      vaccination was not statistically significantly associated with a higher risk of
      any outcome during the entire follow-up. CONCLUSIONS: This study found no
      significantly increased risk for the selected outcomes after the HPV vaccination
      in girls 11-15 years of age. These results provide valid evidence to
      counterbalance public scepticism, fears of adverse events and possible opposition
      to HPV vaccination and consequently can contribute to increase HPV vaccination
      coverage in Finland as well as elsewhere.

PMID- 30115523
TI  - Adherence to pneumococcal conjugate vaccination schedule and uptake rate as
      compared to the established diphtheria-tetanus-acellular pertussis vaccination in
      Cyprus.
AB  - BACKGROUND: Pneumococcus is a common cause of invasive and non-invasive
      infections in children. In areas with high vaccination coverage, universal infant
      vaccination with conjugated pneumococcal vaccine (PCV) has significantly
      decreased the incidence of vaccine type nasopharyngeal carriage and invasive
      pneumococcal disease. The aim of this study is to examine immunization coverage
      rate and timely administration of the recently introduced PCV and compare to the
      established diphtheria-tetanus-acellular pertussis vaccine (DTaP) with similar
      schedule. METHODS: A stratified random sample of healthy infants and children 6
      36 months of age were recruited. Demographic data were collected from parents.
      Among enrolled children, immunization status for DTaP and PCV was noted from the
      child's health booklet. RESULTS: Of 1105 children enrolled in the study, 586
      (53%) were vaccinated in the private sector and the rest in the public sector. A
      significant higher proportion of children vaccinated at the private sector were
      fully vaccinated for PCV (71% versus 58%, p < 0.05) while no difference in the
      DTaP coverage was observed. Conversely, the compliance to the recommended
      vaccination schedule was much higher in the public sector for the first and
      second dose of PCV and second dose of DTaP. The overall, timely administration
      was higher for the DTaP vaccine when compared to PCV (p < 0.05). Moreover,
      adherence to the program was higher for the firstborn child of the family while
      significant differences were observed between different geographic regions.
      Interestingly, co-administration of DTaP and PCV was observed in only 2% of the
      children. CONCLUSION: In children residing in Cyprus, vaccination coverage and
      adherence to PCV vaccination schedule are significantly lower compared to the
      established DTaP vaccine. There is an urgent need for increasing the overall
      vaccination coverage as well as improving the adherence to vaccination schedule.
      Possible interventions are proposed.

PMID- 30115526
TI  - Glycaemic control in native Kuwaiti Arab patients with type 2 diabetes.
AB  - AIMS: To evaluate the influence of age at diabetes diagnosis, diabetes duration,
      BMI, comorbidity with hypertension and medication regimen on glycaemic control in
      native Kuwaiti Arab patients with T2D. METHODS: This cross-sectional study
      considered 7657 patients from Kuwait Diabetes Registry and analysed data from
      their laboratory and hospital records. RESULTS: HbA1c and prevalence of
      hypertension increased significantly with diabetes duration. Duration of diabetes
      (beta=0.034; P<0.001) and age at diagnosis (beta=-0.03; P<0.001) were
      independently associated with HbA1c. Inadequate glycaemic control was more likely
      in patients diagnosed at <60 than in those >=60 years of age (OR:1.80, 95%
      CI:1.39-2.31). Increasing duration of diabetes witnessed decrease in metformin
      prescription and increase in sulfonylureas prescription; proportion of patients
      treated with insulin increased from 5.6% to 44.4% in 9 years of diagnosis.
      Patients with 9-years duration of diabetes or with combination therapy of insulin
      metformin-sulfonylureas differed in mean BMI for adequate or inadequate glycaemic
      control (29.5 versus 31.2kg/m2; P<0.001 and 29.8 versus 33.2; P<0.01,
      respectively). CONCLUSIONS: Only 25.6% of the T2D patients in this ethnic cohort
      exhibited adequate glycaemic control. The delineated relationship of inadequate
      glycaemic control with diabetes duration, onset age, obesity and hypertension
      prevalence has a bearing on diabetes management programs for Arabs.

PMID- 30115528
TI  - Foam cell formation: A new target for fighting atherosclerosis and cardiovascular
      disease.
AB  - During atherosclerosis, the gradual accumulation of lipids into the
      subendothelial space of damaged arteries results in several lipid modification
      processes followed by macrophage uptake in the arterial wall. The way in which
      these modified lipoproteins are dealt with determines the likelihood of
      cholesterol accumulation within the monocyte-derived macrophage and thus its
      transformation into the foam cell that makes up the characteristic fatty streak
      observed in the early stages of atherosclerosis. The unique expression of
      chemokine receptors and cellular adhesion molecules expressed on the cell surface
      of monocytes points to a particular extravasation route that they can take to
      gain entry into atherosclerotic site, in order to undergo differentiation into
      the phagocytic macrophage. Indeed several GWAS and animal studies have identified
      key genes and proteins required for monocyte recruitment as well cholesterol
      handling involving lipid uptake, cholesterol esterification and cholesterol
      efflux. A re-examination of the previously accepted paradigm of macrophage foam
      cell origin has been called into question by recent studies demonstrating shared
      expression of scavenger receptors, cholesterol transporters and pro-inflammatory
      cytokine release by alternative cell types present in the neointima, namely;
      endothelial cells, vascular smooth muscle cells and stem/progenitor cells. Thus,
      therapeutic targets aimed at a more heterogeneous foam cell population with
      shared functions, such as enhanced protease activity, and signalling pathways,
      mediated by non-coding RNA molecules, may provide greater therapeutic outcome in
      patients. Finally, studies targeting each aspect of foam cell formation and death
      using both genetic knock down and pharmacological inhibition have provided
      researchers with a clearer understanding of the cellular processes at play, as
      well as helped researchers to identify key molecular targets, which may hold
      significant therapeutic potential in the future.

PMID- 30115530
TI  - Pirfenidone increases the epithelialization rate of skin graft donor sites.
AB  - BACKGROUND: Improving epithelialization of donor sites of split-thickness skin
      grafts (STSG) is extremely important in burned patients. We aimed to assess the
      efficacy of pirfenidone, a drug with anti-inflammatory, antifibrotic, and
      antioxidant effects, to accelerate wound healing. We hypothesized that
      pirfenidone accelerates the epithelialization rates in donor sites. METHODS: We
      included 28 patients requiring STSGs with donor sites of at least 7.5*10cm. After
      harvesting, the donor sites were randomly treated with either non-adherent gauze
      or topical pirfenidone and covered with non-adherent gauze. To assess
      epithelialization, biopsies were taken at day 7 and 10 on the pirfenidone group,
      and at day 10 on the control group. Percentage of epithelialization was assessed
      on the same days through clinical photographs. The pathologists and the clinical
      observer were blinded to the group and timepoint of the samples. RESULTS: 24
      patients were included in the study, with a median age of 21(5-73) for control
      group and 28(9-61) for pirfenidone. The thickness of epithelium was 75.10+/-60MUm
      at day 10 for the control group; and 98.21+/-6MUm at day 7, and 108+/-22MUm at
      day 10 for the pirfenidone group (p=<0.05). Epithelization rate was 83.58+/
      14.09% at day 10 for the control group; and 98.7+/-1.8% at day 7, and 99.5+/-1.6%
      at day 10 for the pirfenidone group. CONCLUSIONS: Pirfenidone is efficient in
      reducing the healing times when applied in STSG donor sites, at both days 7 and
      10.

PMID- 30115531
TI  - Trends and inpatient outcomes for palliative care services in major burn
      patients: A 10-year analysis of the nationwide inpatient sample.
AB  - INTRODUCTION: Despite advances in critical care and the surgical management of
      major burns, highly moribund patients are unlikely to survive. Little is known
      regarding the utilization and effects of palliative care services in this
      population. METHODS: All major burn hospitalizations were identified within the
      Nationwide Inpatient Sample. Patients were characterized by burn, demographic,
      facility, and diseases factors. Palliative care services were identified with
      International Classification Disease 9th edition code V6.67. Temporal trends were
      assessed with Poisson modeling. Inpatient mortality and death without surgical
      intervention were assessed with logistic regression. Outcomes were stratified by
      modified Baux scores. RESULTS: 7424 major burns were included; 1.9% received
      palliative care services. Patients receiving palliation had a mean age of 63.6
      years (SD 19.6), mean total body surface area of 62.2% (SD 24.9%), and mean
      modified Baux score of 127.1 (SD 26.7). Adjusting for covariates, the incidence
      rate ratio was 1.42 over the 10-year period (95% CI, 1.31-1.54, p<0.001).
      Independent predictors of palliative consultations included older age, larger
      burns, deeper burns, and higher Elixhauser comorbidity score. Among patients with
      modified Baux scores between 100-153, those receiving palliative care services
      were significantly more likely to die without surgery, OR 3.24 (95% CI 1.13
      10.39, p=0.029), with no significant difference in mortality, OR 11.72 (95% CI
      0.87-22.57, p=0.051) CONCLUSION AND RELEVANCE: Palliative care services were
      increasingly used during the study period. Palliative care services in highly
      moribund burn patients do not impact survival and may decrease the likelihood of
      surgical intervention in select patients.

PMID- 30115529
TI  - Understanding context dependency in the response of forest understorey plant
      communities to nitrogen deposition.
AB  - Understorey communities can dominate forest plant diversity and strongly affect
      forest ecosystem structure and function. Understoreys often respond sensitively
      but inconsistently to drivers of ecological change, including nitrogen (N)
      deposition. Nitrogen deposition effects, reflected in the concept of critical
      loads, vary greatly not only among species and guilds, but also among forest
      types. Here, we characterize such context dependency as driven by differences in
      the amounts and forms of deposited N, cumulative deposition, the filtering of N
      by overstoreys, and available plant species pools. Nitrogen effects on
      understorey trajectories can also vary due to differences in surrounding
      landscape conditions; ambient browsing pressure; soils and geology; other
      environmental factors controlling plant growth; and, historical and current
      disturbance/management regimes. The number of these factors and their potentially
      complex interactions complicate our efforts to make simple predictions about how
      N deposition affects forest understoreys. We review the literature to examine
      evidence for context dependency in N deposition effects on forest understoreys.
      We also use data from 1814 European temperate forest plots to test the ability of
      multi-level models to characterize context-dependent understorey responses across
      sites that differ in levels of N deposition, community composition, local
      conditions and management history. This analysis demonstrated that historical
      management, and plot location on light and pH-fertility gradients, significantly
      affect how understorey communities respond to N deposition. We conclude that
      species' and communities' responses to N deposition, and thus the determination
      of critical loads, vary greatly depending on environmental contexts. This
      complicates our efforts to predict how N deposition will affect forest
      understoreys and thus how best to conserve and restore understorey biodiversity.
      To reduce uncertainty and incorporate context dependency in critical load
      setting, we should assemble data on underlying environmental conditions, conduct
      globally distributed field experiments, and analyse a wider range of habitat
      types.

PMID- 30115532
TI  - How long are burn patients really NPO in the perioperative period and can we
      effectively correct the caloric deficit using an enteral feeding "Catch-up"
      protocol?
AB  - OBJECTIVE: "NPO at midnight" is a standard preoperative practice intended to
      reduce aspiration risk but can result in prolonged feeding interruptions in
      critically ill burn patients. Postoperative hyperalimentation in the form of a
      "catch-up" tube feeding protocol is routine. A retrospective review of our
      perioperative fasting practices and "catch-up" enteral feeding protocols was
      performed. METHODS: Patients admitted to the Burn ICU from July 1st, 2015 to
      August 31st, 2016 were reviewed. Patients who had a protected airway in place,
      prescribed enteral nutrition, and underwent surgery were included. The time from
      NPO to surgical start (NPO-SS), NPO to feeding restart (NPO-FR), and calories
      received/prescribed were quantified. The efficacy of a postoperative catch-up
      feeding protocol was analyzed. RESULTS: There were 41 patients that fit inclusion
      criteria with some undergoing multiple surgeries, yielding 109 surgeries/discrete
      perioperative events. The average total body surface area burn (38.1+/-23.6%),
      age (38.8+/-20.1years), ICU days (45.0+/-37.3 days), and ventilator days (35.1+/
      33.8 days) were calculated. Average fasting durations of NPO-SS and NPO-FR were
      9.3+/-3.1 and 14.2+/-4.1h, respectively. The average caloric deficit to
      prescribed calories ratio during the NPO-SS and NPO-FR periods were 1154+/
      629/3534+/-851kcal and 1765+/-928/3534+/-851kcal, respectively. A post-operative
      catch-up protocol completely compensated for perioperative caloric deficits 68.8%
      (22/32) of the time. CONCLUSIONS: In critically ill burn patients, a preoperative
      fast resulted in an average loss of greater than 50% of prescribed calories on
      the day of surgery. Clinicians should re-evaluate the standard practice of making
      preoperative patients "NPO at midnight". An effective catch-up protocol can
      adequately reduce caloric deficits.

PMID- 30115533
TI  - Assessing condition and ecological role of deep-water biogenic habitats: Glass
      sponge reefs in the Salish Sea.
AB  - Biogenic habitats play important roles in shallow-water ecosystems, but their
      roles in deeper waters are less well-studied. We quantitatively assessed 19 glass
      sponge reefs in the Salish Sea for live reef-building sponge cover and
      biodiversity, explored potential drivers behind variation observed among reefs,
      and quantified individual and collective roles the reefs play in filtration and
      carbon removal. The reefs support diverse and abundant communities of
      invertebrates and fish, with 115 unique taxonomic groups observed. Sponge cover
      varied widely between reefs: percent live reef-building sponge cover ranged from
      0.2 to 17.5% and proportion of live reef habitat category ranged from 0.2 to 92%.
      These differences were predominantly driven by the seabed terrain characteristics
      such as seafloor rugosity, curvature, and depth; human pressure measures explored
      in this study - density of anthropogenic objects and fishing footprint over the
      past 17 years - did not mask the natural influence of seabed terrain. The
      difference in sponge cover between the reefs led to wide variation in ecosystem
      function with individual reefs processing between 465 and 47,300 L/m2 per day.
      Collectively, each day the 19 reefs filter 1.04 * 1011 L of water which
      corresponds to 1% of the total water volume in Strait of Georgia and Howe Sound
      combined. The reefs remove up to 1 g of carbon per m2 per day, comparable to
      carbon sequestration rates reported for terrestrial old growth forests and to
      "blue carbon" sequestration rates by marine vegetation. Implications for sponge
      reef conservation and monitoring are discussed.

PMID- 30115527
TI  - Interferon alpha: The key trigger of type 1 diabetes.
AB  - IFNalpha is a cytokine essential to a vast array of immunologic processes. Its
      induction early in the innate immune response provides a priming mechanism that
      orchestrates numerous subsequent pathways in innate and adaptive immunity.
      Despite its beneficial effects in viral infections IFNalpha has been reported to
      be associated with several autoimmune diseases including autoimmune thyroid
      disease, systemic lupus erythematosus, rheumatoid arthritis, primary biliary
      cholangitis, and recently emerged as a major cytokine that triggers Type 1
      Diabetes. In this review, we dissect the role of IFNalpha in T1D, focusing on the
      potential pathophysiological mechanisms involved. Evidence from human and mouse
      studies indicates that IFNalpha plays a key role in enhancing islet expression of
      HLA-I in patients with T1D, thereby increasing autoantigen presentation and beta
      cell activation of autoreactive cytotoxic CD8 T-lymphocytes. The binding of
      IFNalpha to its receptor induces the secretion of chemokines, attracting
      monocytes, T lymphocytes, and NK cells to the infected tissue triggering
      autoimmunity in susceptible individuals. Furthermore, IFNalpha impairs insulin
      production through the induction of endoplasmic reticulum stress as well as by
      impairing mitochondrial function. Due to its central role in the early phases of
      beta cell death, targeting IFNalpha and its pathways in genetically predisposed
      individuals may represent a potential novel therapeutic strategy in the very
      early stages of T1D.

PMID- 30115534
TI  - Prediction of solar irradiance using ray-tracing techniques for coral macro- and
      micro-habitats.
AB  - Light distribution on coral reefs is very heterogeneous at the microhabitat level
      and is an important determinant of coral thermal microenvironments. This study
      implemented a solar load model that uses a backward ray-tracing method to
      estimate macroscale and microscale variations of solar irradiance penetrating the
      ocean surface and impacting the surfaces of coral colonies. We then explored
      whether morphological characteristics such as tissue darkness (or pigmentation)
      and thickness may influence the amount of light captured and its spectral
      distribution by two contrasting coral colony morphologies, branching and massive.
      Results of global horizontal irradiance above and below the sea-surface and at
      the surface of coral colonies were validated using spectrometer scans, field
      measurements, and empirical correlations. The macroscale results of horizontal,
      irradiated, and shaded irradiance levels and solar altitude angles for PAR, UVA
      and UVB compared very well with the spectrometer-based observations (typically
      within < 5%). In general, a comparison between the model results and field and
      empirical measurements indicated that the contributions of clouds, turbidity, and
      tides to variations in irradiance at various depth (up to 5 m) were typically
      within 5-10% of each other. Moreover, the effect of colony darkness or
      pigmentation on light microenvironment was notably more pronounced for the
      massive species than branching colony. This study provided insights that species
      with thinner tissue have the ability to intercept more light with the difference
      in terms of irradiance levels between 0.1 mm and 0.8 mm tissue thickness for both
      massive and branching colonies were approximately 2 W m-2, which was quite
      unlikely to influence the overall coral heat budgets.

PMID- 30115535
TI  - Differential sensitivity of larvae to ocean acidification in two interacting
      mollusc species.
AB  - Anthropogenically-induced ocean acidification (OA) scenarios of decreased pH and
      altered carbonate chemistry are threatening the fitness of coastal species and
      hence near-shore ecosystems' biodiversity. Differential tolerances to OA between
      species at different trophic levels, for example, may alter species interactions
      and impact community stability. Here we evaluate the effect of OA on the larval
      stages of the rock oyster, Saccostrea cucullata, a dominant Indo-Pacific
      ecosystem engineer, and its key predator, the whelk, Reishia clavigera. pH as low
      as 7.4 had no significant effect on mortality, abnormality or growth of oyster
      larvae, whereas whelk larvae exposed to pH 7.4 experienced increased mortality
      (up to ~30%), abnormalities (up to 60%) and ~3 times higher metabolic rates
      compared to controls. Although these impacts' long-term consequences are yet to
      be investigated, greater vulnerability of whelk larvae to OA could impact
      predation rates on intertidal rocky shores, and have implications for subsequent
      community dynamics.

PMID- 30115536
TI  - Overexpression of UQCRC2 is correlated with tumor progression and poor prognosis
      in colorectal cancer.
AB  - Ubiquinol-cytochrome c reductase complex core protein 2 (UQCRC2) is an important
      subunit of mitochondrial respiratory complex III. However, its role in
      tumorigenesis and tumor progression remains unknown, especially with regards to
      colorectal cancer (CRC). In this research, we measured the expression of UQCRC2
      protein by immunohistochemistry assay in 89 paired paraffin-embedded tumor
      tissues and corresponding adjacent normal tissues from patients with colorectal
      adenocarcinoma and investigated possible correlations of UQCRC2 expression with
      clinicopathological parameters and prognosis. We found that UQCRC2 was
      significantly upregulated in CRC tissues compared with adjacent normal tissues,
      and immunohistochemical UQCRC2 status was correlated to the depth of invasion
      (T), lymph node metastasis (N), advanced TNM stage. Multivariate analysis
      indicated that UQCRC2 remained an independent prognostic factor for poorer
      overall survival. Furthermore, we determined the role of UQCRC2-knockdown in CRC
      cells (RKO and HCT116) using lentivirus-mediated small hairpin RNAs (shRNAs). The
      effects of UQCRC2 knockdown on CRC cells (RKO and HCT116) proliferation were
      analyzed by cell proliferation and colony formation assay, and cell cycle and
      apoptosis were assessed by flow cytometry. We found that silencing UQCRC2
      suppressed cell proliferation and colony formation in RKO and HCT116 cells, led
      to a cell cycle arrest and induced cell apoptosis in vitro. These results
      provided novel insights into the potential role of UQCRC2 in the tumorigenesis
      and progression of CRC, and revealed that UQCRC2 may serve as a new prognostic
      and therapeutic target in CRC.

PMID- 30115537
TI  - Expression of TUSC3 and its prognostic significance in colorectal cancer.
AB  - BACKGROUND: Colorectal cancer (CRC) is one of the most common cancers worldwide.
      Tumor suppressor candidate 3 (TUSC3) has been reported be associated with
      embryogenesis and metabolism. The aim of this study is to investigate the
      expression of TUSC3 in CRC tissues, and to evaluate the clinical pathological
      characters and prognostic significance. METHOD: First, we performed a
      bioinformatics analysis by using Oncomine and COEXPEDIA databases. Gene Set
      Enrichment Analysis (GSEA) was performed using TCGA data set. Then, the protein
      expression level of TUSC3 was detected by immunohistochemistry in 230 pairs of
      primary colorectal cancer and corresponding non-tumor tissues. RESULT: We
      investigated Oncomine databases and found that TUSC3 mRNA expression was
      significantly higher in CRC tissues compared with normal tissues. The
      immunohistochemistry results demonstrated that TUSC3 was overexpressed in the CRC
      tissues. Furthermore, TUSC3 overexpression was associated with T stage, lymph
      node metastasis, and distant metastasis. TUSC3 overexpression was associated with
      worse overall survival for CRC, and retained significance as an independent
      prognostic factor for CRC. Bioinformatics analysis indicated that TUSC3
      expression was associated with epithelial-mesenchymal transition signaling
      pathway and TUSC3 co-expression genes were obtained from COEXPEDIA. CONCLUSION:
      TUSC3 may act as an oncogene in the progression of colorectal cancer. Moreover,
      TUSC3 has potential to be used as prognostic markers or therapeutic targets in
      CRC.

PMID- 30115538
TI  - Possible mechanisms mediating apoptosis of bronchial epithelial cells in chronic
      obstructive pulmonary disease - A next-generation sequencing approach.
AB  - PURPOSE: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory
      airway disease characterized by persistent airflow limitation. Apoptosis of
      pulmonary structural cells contributes to pulmonary destruction and dysfunction.
      This study aimed to explore the possible mechanisms underlying decreased cell
      proliferation and increased apoptosis of bronchial epithelial cells of COPD.
      MATERIALS AND METHODS: The expression profiles of mRNAs and microRNAs in
      bronchial epithelial cells from a COPD patient and a normal subject were
      identified using next-generation sequencing (NGS) and analyzed using
      bioinformatic tools. RESULTS: We identified 233 significantly upregulated and 204
      significantly downregulated genes in COPD bronchial epithelial cells. The PI3K
      Akt pathway was one of the most important dysregulated pathways in bronchial
      epithelial cells. We further identified that 3 genes involved in the PI3K-Akt
      signaling pathway, including IL6, F2R, and FGFR3, might be associated with
      inhibition of cell proliferation in bronchial epithelial cells, while 5 genes
      involved in the PI3K-Akt signaling pathway, including TLR4, IL6, F2R, FGFR3, and
      FGFR1, might be associated with apoptosis of bronchial epithelial cells. FGFR1
      was also a predicted target for some up-regulated miRNAs in COPD bronchial
      epithelial cells, including hsa-miR-195-5p, hsa-miR-424-5p, and hsa-miR-6724-5p.
      CONCLUSION: Our findings suggest PI3K-Akt signaling pathway plays an important
      role in COPD. We observed altered expression of apoptosis and cell proliferation
      related genes that might contribute to the pathogenesis of COPD.

PMID- 30115539
TI  - MRI-based treatment planning for brain stereotactic radiosurgery: Dosimetric
      validation of a learning-based pseudo-CT generation method.
AB  - Magnetic resonance imaging (MRI)-only radiotherapy treatment planning is
      attractive since MRI provides superior soft tissue contrast without ionizing
      radiation compared with computed tomography (CT). However, it requires the
      generation of pseudo CT from MRI images for patient setup and dose calculation.
      Our machine-learning-based method to generate pseudo CT images has been shown to
      provide pseudo CT images with excellent image quality, while its dose calculation
      accuracy remains an open question. In this study, we aim to investigate the
      accuracy of dose calculation in brain frameless stereotactic radiosurgery (SRS)
      using pseudo CT images which are generated from MRI images using the machine
      learning-based method developed by our group. We retrospectively investigated a
      total of 19 treatment plans from 14 patients, each of whom has CT simulation and
      MRI images acquired during pretreatment. The dose distributions of the same
      treatment plans were calculated on original CT simulation images as ground truth,
      as well as on pseudo CT images generated from MRI images. Clinically-relevant DVH
      metrics and gamma analysis were extracted from both ground truth and pseudo CT
      results for comparison and evaluation. The side-by-side comparisons on image
      quality and dose distributions demonstrated very good agreement of image contrast
      and calculated dose between pseudo CT and original CT. The average differences in
      Dose-volume histogram (DVH) metrics for Planning target volume (PTVs) were less
      than 0.6%, and no differences in those for organs at risk at a significance level
      of 0.05. The average pass rate of gamma analysis was 99%. These quantitative
      results strongly indicate that the pseudo CT images created from MRI images using
      our proposed machine learning method are accurate enough to replace current CT
      simulation images for dose calculation in brain SRS treatment. This study also
      demonstrates the great potential for MRI to completely replace CT scans in the
      process of simulation and treatment planning.

PMID- 30115540
TI  - Blurring lines between treatment intensity and patient fitness in elderly people
      with AML.

PMID- 30115542
TI  - Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB
      activation: Potential roles in amyloidosis?
AB  - The cascade of molecular events leading to Human apolipoprotein A-I (apoA-I)
      amyloidosis is not completely understood, not even the pathways that determine
      clinical manifestations associated to systemic protein deposition in organs such
      as liver, kidney and heart. About twenty natural variants of apoA-I were
      described as inducing amyloidosis, but the mechanisms driving their aggregation
      and deposition are still unclear. We previously identified that the mutant
      Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen
      species from cultured RAW 264.7 murine macrophages, suggesting that part of the
      pathogenic pathway could elicit of an inflammatory signal. In this work we gained
      deep insight into this mechanism and determined that Gly26Arg induced a specific
      pro-inflammatory cascade involving activation of NF-kappaB and its translocation
      into the nucleus. These findings suggest that some but not all apoA-I natural
      variants might promote a pro-oxidant microenvironment which could in turn result
      in oxidative processing of the variants into a misfolded conformation.

PMID- 30115543
TI  - Escherichia coli causing meningitis in an adult: A case report and experimental
      characterization of its virulence.

PMID- 30115544
TI  - Salvage Chemotherapy With Gemcitabine, Paclitaxel, Ifosfamide, and Cisplatin for
      Relapsed Germ Cell Cancer.
AB  - BACKGROUND: Metastatic germ cell tumors remain potentially curable when treated
      with salvage chemotherapy at first relapse. In the present phase I/II study, we
      sought to improve on the response rate and duration of the TIP (paclitaxel,
      ifosfamide, cisplatin) regimen by adding gemcitabine (Gem-TIP). MATERIALS AND
      METHODS: Twenty patients were recruited after failure of first-line cisplatin
      containing chemotherapy. The primary objectives were to determine the maximum
      tolerated dose of gemcitabine when combined with TIP and to establish the dose
      intensity of the TIP drugs in this combination. The secondary objectives were the
      response rates, failure-free survival, and overall survival. RESULTS: The maximum
      tolerated dose of gemcitabine was 1200 mg/m2. The mean relative dose intensity
      was 95% (95% confidence interval [CI], 90.2%-99.2%) for gemcitabine, 96% (95% CI,
      92.9%-98.7%) for paclitaxel, 92% (95% CI, 84.5%-98.8%) for ifosfamide, and 94%
      (95% CI, 89.3%-99.0%) for cisplatin. The overall complete response rate was 50%;
      another 30% of the patients achieved a partial response. The 1-year failure-free
      survival and overall survival rates were 68% (95% CI, 43%-84%) and 89.5% (95% CI,
      64%-97%), respectively. CONCLUSION: Gemcitabine can be added to TIP chemotherapy
      at the full dose, with manageable toxicity and no detrimental effect on the dose
      intensity of the TIP drugs. The response rate and duration were improved compared
      with those reported from the Medical Research Council TIP trial; further
      evaluation is warranted.

PMID- 30115541
TI  - Cladribine and low-dose cytarabine alternating with decitabine as front-line
      therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm
      trial.
AB  - BACKGROUND: Front-line therapy for elderly or unfit patients with acute myeloid
      leukaemia (AML) remains unsatisfactory with poor outcomes and excessive toxicity.
      We studied a new low-intensity regimen of cladribine combined with low-dose
      cytarabine alternating with decitabine, aimed at improving outcomes in this
      population. Based on our previous experience, we hypothesised that this
      combination would be safe and more effective than current approaches with
      hypomethylating agents. METHODS: In this single-arm, open-label, single-centre
      phase 2 study, we enrolled patients aged 60 years or older with previously
      untreated AML or high-risk myelodysplastic syndrome who had adequate organ
      function and an Eastern Cooperative Oncology Group performance status of 2 or
      less. Patients were treated with cladribine plus low-dose cytarabine for two 28
      day cycles alternating with decitabine for two 28-day cycles, for up to 18
      cycles. Induction therapy (cycle 1) consisted of cladribine 5 mg/m2 intravenously
      over 1-2 h on days 1-5 and cytarabine 20 mg subcutaneously twice daily on days 1
      10. Patients who had remission during this induction regimen moved on to
      consolidation therapy (cladribine 5 mg/m2 intravenously over 1-2 h on days 1-3
      and cytarabine 20 mg twice daily on days 1-10, alternating with decitabine 20
      mg/m2 intravenously on days 1-5). The primary outcome measure was disease-free
      survival. Secondary outcomes were overall survival, proportion of patients
      achieving complete response, proportion of patients achieving response, toxicity,
      and induction mortality. All treated patients were included in the analyses. This
      trial is ongoing and is registered with ClinicalTrials.gov, number NCT01515527.
      FINDINGS: Between Feb 17, 2012, and July 6, 2017, 118 patients were enrolled and
      treated, among whom 48 (41%) had an adverse karyotype, 20 (17%) had therapy
      related AML, 18 (15%) had treated secondary AML, and 20 (17%) had TP53 mutations.
      Median disease-free survival was 10.8 months (IQR 5.4-25.9). 80 (68%) patients
      achieved objective response: 69 (58%) achieved a complete response and 11 (9%)
      patients had complete response with incomplete count recovery. The median overall
      survival was 13.8 months (6.9-28.6). The regimen was well tolerated, with one
      (1%) death within the first 4 weeks and eight (7%) deaths within the first 8
      weeks. The most common non-haematological adverse events of grade 3 or worse were
      infection (88 [75%] patients), elevated total bilirubin (26 [22%] patients), rash
      (13 [11%] patients), and nausea (13 [11%] patients). INTERPRETATION: The
      combination of cladribine and low-dose cytarabine alternating with decitabine
      appears to be a safe and highly effective regimen for the treatment of elderly or
      unfit patients with newly diagnosed AML. Further testing of this regimen is
      warranted, and could help to provide a new, effective option for reduced
      intensity therapy in this population. FUNDING: Part supported by the National
      Institutes of Health.

PMID- 30115545
TI  - Ruxolitinib Rechallenge Can Improve Constitutional Symptoms and Splenomegaly in
      Patients With Myelofibrosis: A Case Series.
AB  - INTRODUCTION: Myelofibrosis (MF) is one of the classic myeloproliferative
      neoplasms and can occur de novo or following transformation from polycythemia
      vera (PPV MF) or essential thrombocythemia (PET MF). It can be associated with
      constitutional symptoms and splenomegaly, both of which can negatively impact
      quality of life. The only curative option for MF is allogeneic stem cell
      transplantation. Studies have shown that JAK2 inhibitors such as ruxolitinib are
      effective in reducing both splenomegaly and symptom burden. Although there is no
      approved treatment for patients who progress on ruxolitinib, anecdotal evidence
      suggests patients may respond to a re-challenge of ruxolitinib after drug
      cessation. PATIENTS AND METHODS: We conducted a multi-institutional,
      retrospective case series to study patients who were re-challenged with
      ruxolitinib after inadequate response to or loss of response with an initial
      treatment course. Thirteen patients were identified. Six patients had primary MF,
      3 patients had PPV MF, and 4 patients had PET MF. Ten patients were JAK2
      positive, 2 were CALR-positive, and 1 patient had neither mutation. Nine patients
      received 1 ruxolitinib re-challenge, and 4 received 2 re-challenges. Response was
      defined as improvement in constitutional symptoms and/or reduction in spleen
      size. RESULTS: During the primary treatment course with ruxolitinib, there was
      improvement in constitutional symptoms and reduction in spleen size in 92% and
      85% of patients, respectively. Following cessation of ruxolitinib, all patients
      received a first re-challenge course with improvement in symptoms and
      splenomegaly in 92% and 69%, respectively. Of the 4 patients who received a
      second re-challenge course of ruxolitinib, all had improvements in spleen size
      and constitutional symptoms. Six patients have continued on a first or second
      ruxolitinib re-challenge course with good response. CONCLUSION: Our study
      demonstrates that re-exposure to ruxolitinib following a period of treatment
      cessation in patients with MF can lead to durable responses with regards to both
      splenomegaly and symptom burden.

PMID- 30115547
TI  - Microevolution of epidemiological highly relevant non-O157 enterohemorrhagic
      Escherichia coli of serogroups O26 and O111.
AB  - Enterohemorrhagic Escherichia coli (EHEC) are a cause of bloody diarrhea,
      hemorrhagic colitis (HC) and the potentially fatal hemolytic uremic syndrome
      (HUS). While O157:H7 is the dominant EHEC serotype, non-O157 EHEC have emerged as
      serious causes of disease. In Germany, the most important non-O157 O-serogroups
      causing one third of EHEC infections, including diarrhea as well as HUS, are O26,
      O103, O111 and O145. Interestingly, we identified EHEC O-serogroups O26 and O111
      in one single sequence type complex, STC29, that also harbours atypical
      enteropathogenic E. coli (aEPEC). aEPEC differ from typical EHEC merely in the
      absence of stx-genes. These findings inspired us to unravel a putative
      microevolutionary scenario of these non-O157 EHEC by whole genome analyses.
      Analysis of single nucleotide polymorphisms (SNPs) of the maximum common genome
      (MCG) of 20 aEPEC (11 human/ 9 bovine) and 79 EHEC (42 human/ 36 bovine/ 1 food
      source) of STC29 identified three distinct clusters: Cluster 1 harboured strains
      of O-serogroup O111, the central Cluster 2 harboured only O26 aEPEC strains,
      while the more heterogeneous Cluster 3 contained both EHEC and aEPEC strains of O
      serogroup O26. Further combined analyses of accessory virulence associated genes
      (VAGs) and insertion sites for mobile genetic elements suggested a parallel
      evolution of the MCG and the acquisition of virulence genes. The resulting
      microevolutionary model suggests the development of two distinct EHEC lineages
      from one common aEPEC ancestor of ST29 by lysogenic conversion with stx
      converting bacteriophages, independent of the host species the strains had been
      isolated from. In conclusion, our cumulative data indicate that EHEC of O
      serogroups O26 and O111 of STC29 originate from a common aEPEC ancestor and are
      bona fide zoonotic agents. The role of aEPEC in the emergence of O26 and O111
      EHEC should be considered for infection control measures to prevent possible
      lysogenic conversion with stx-converting bacteriophages as major vehicle driving
      the emergence of EHEC lineages with direct Public Health consequences.

PMID- 30115548
TI  - More than the Sum of its Parts: Perception and Neuronal Underpinnings of Sequence
      Processing.

PMID- 30115549
TI  - Effects of corneoscleral topography on soft contact lens performance: A pilot
      study.
AB  - To quantify corneoscleral junction (CSJ) topography in soft contact lens (SCL)
      wearers, and assess the association between the CSJ and SCL performance and
      subjective comfort, forty-four adapted SCL wearers (16 Asians, 16 Caucasians, 12
      Latinos) were recruited for the present study. Corneal topography was taken with
      a Medmont E300 (Medmont International, Pty Ltd.). CSJ images were taken with a
      commercial OCT (Bioptigen, Inc.). Our published CSJ image analysis technique was
      used to describe the geometric properties of the CSJ using the sum of squared
      orthogonalized residuals (SSRo). Multivariable mixed effects models were employed
      to examine associations between SSRo and subject demographics, ocular
      characteristics, SCL fit and performance, and comfort. The SSRo was significantly
      related to quadrant (p < 0.001), ethnicity (p = 0.014), and horizontal corneal
      shape factor (p = 0.044). The nasal quadrant had the largest SSRo, indicating the
      steepest CSJ profile and/or the most irregular CSJ surface, followed by the
      inferior quadrant. The superior and temporal quadrants had the smallest SSRo,
      indicating relatively flat and even CSJ topography. Caucasians had the steepest
      and/or most irregular CSJ compared with Latinos and Asians. Less inferior
      superior heterogeneity in the SSRo was associated with greater comfort after 6 h
      of lens wear. The SSRo was proved to be a useful tool to quantify CSJ geometry in
      SCL wearers. Significant differences in the SSRo were found among quadrants and
      ethnic groups. Better subjective comfort after 6 h of SCL wear was associated
      with a smaller difference in the SSRo between the superior and inferior
      quadrants.

PMID- 30115546
TI  - A critical analysis of risk factors for necrotizing enterocolitis.
AB  - Necrotizing enterocolitis (NEC) is the most common serious gastrointestinal
      morbidity in preterm infants. A number of risk factors for NEC have been reported
      in the literature. With the exception of decreasing gestational age, decreasing
      birth weight and formula feeding, there is disagreement on the importance of
      reported risk factors with uncertain causality. Causal risk factors may be
      observed at any time before the onset of NEC, including prior to an infant's
      birth. The purpose of this review is to examine the existing literature and
      summarize risk factors for NEC. This review may be helpful in understanding the
      epidemiology of NEC and inform the measurement and assessment of risks factors
      for NEC in research studies and quality improvement projects.

PMID- 30115550
TI  - BMI is a misleading proxy for adiposity in longitudinal studies with adolescent
      males: The Australian LOOK study.
AB  - OBJECTIVES: Despite evidence suggesting caution, employment of body mass index
      (BMI, kgm-2) as a proxy for percentage of body fat (PFat) in longitudinal studies
      of children and adolescents remains commonplace. Our objective was to test the
      validity of change in BMI as a proxy for change in PFat measured by dual-energy X
      ray absorptiometry (DXA) during adolescence. DESIGN: Longitudinal study. METHODS:
      Healthy, predominantly Australian youth of mainly Caucasian background (131
      females and 115 males) underwent repeated measures at 12.0 (SD 0.3) and 16.0 (SD
      0.3) years for height, weight and PFat (DXA). RESULTS: There was no significant
      difference in the percentage changes in BMI and PFat for the females (beta=2.45,
      standard error (SE)=1.39, 95% confidence interval (CI)=[-0.27; 5.17]) with their
      mean BMI increasing 15% as their mean PFat increased 18%. However, for the males,
      while their mean BMI also increased 15%, their mean PFat was reduced 25%; this
      change being highly significant (beta=-42.25, SE=2.23, 95% CI=[-46.22, -38.27]).
      CONCLUSIONS: While change in BMI is likely to be a rough proxy for change in PFat
      measured by DXA in longitudinal studies of adolescent females, this is not the
      case for adolescent males, where increased BMI is likely to correspond with
      decreased PFat. Consequently, inferences from longitudinal studies of adolescents
      which have assumed that an increase in BMI (or BMI Z-scores or percentiles)
      represents an increase in adiposity require reconsideration.

PMID- 30115551
TI  - [How I do... a low-cost hysteroscopy model].

PMID- 30115552
TI  - [Robotic surgery in endometrial cancer: Feasibility in obese patients].
AB  - OBJECTIVE: Minimally invasive surgery is a technique frequently used in
      gynecologic surgery. The robot-assisted surgery is a recent approach, and the
      benefits are not yet proven. The objective of this study was to evaluate the
      feasibility to use robot-assisted surgery for obese patient with endometrial
      cancer. METHODS: All patients undergoing a robotic surgery for uterus malignant
      indication between March 2013 and May 2016 in our center were retrospectively
      included. Patients were divided in two groups, according to their body mass index
      (BMI). The group with BMI<30kg/m2 was the reference for this comparative study.
      The main criteria was the robot operative time. The other criteria were total
      operating time, hospital stay and intraoperative and postoperative complications.
      RESULTS: Seventy-seven patients met inclusion criteria for analysis. The median
      robot operative time was 110minutes for all patients [21-341], without difference
      between the five groups (P=0.60). There was no difference for the total operative
      time (P=0.50). The median hospital stay was 3 days (P=0.92). There were ten
      intraoperative complications. One patient had a conversion (1.3%). There was no
      statistical difference for postoperative complications (P=1). CONCLUSION: Our
      study found few differences in the surgical management by laparoscopic robot
      assisted between obese and non obese women. Robot-assisted surgery seems to be
      feasible for uterine cancer treatment of obese patients. Prospective and
      randomized studies are needed to assess the benefit of the robotic surgery.

PMID- 30115553
TI  - Adjunctive S-adenosylmethionine (SAMe) in treating non-remittent major depressive
      disorder: An 8-week double-blind, randomized, controlled trial.
AB  - There has been increasing interest in nutraceutical augmentation strategies to
      boost the efficacy of antidepressants. This study assessed whether S
      adenosylmethionine (SAMe), a methyl donor that occurs naturally in the body, may
      be of such benefit. We conducted an 8-week, double-blind RCT in which 107
      treatment non-remittent outpatients with DSM-5 diagnosed Major Depressive
      Disorder (MDD) were randomized to either SAMe or placebo adjunctively to
      antidepressants. One-carbon cycle nutrients, pertinent single nucleotide
      polymorphisms (SNPs), and BDNF were also analysed as potential moderators of
      response. A linear mixed-effects model revealed a significant overall reduction
      in Montgomery-Asberg Depression Rating Scale (MADRS) score across time, however
      there was no significant between-group difference observed (p = 0.51). Response
      rates at Week 8 were 54.3% in the SAMe group and 50.0% in the placebo group, with
      remission rates 43.5% for SAMe and 38.3% for placebo (all results NS). No effect
      of SAMe was found on any secondary outcome. Differential response to SAMe was not
      modified by a range of key genotypes (e.g. COMT), nor reflected in a change of
      homocysteine, red cell folate, or BDNF. Use of SAMe elicited no significant
      adverse effects beyond placebo, however it was implicated in one case of
      serotonin syndrome-like symptoms. This study concludes that 800 mg/day of SAMe is
      not an effective adjunctive treatment in MDD, and no obvious biomarker reflected
      any differential response to treatment. Due to such a distinctly high placebo
      response (despite rigorous screening), future studies should employ a placebo run
      in period and other strategies to minimize placebo response.

PMID- 30115554
TI  - Frequency of regulatory B cells in adipose tissue and peripheral blood from
      individuals with overweight, obesity and normal-weight.
AB  - STATEMENTS OF THE PROBLEM: Regulatory B (Breg) cells have a critical role in
      adipose tissue homeostasis, and although subtypes of Breg cells have been
      described, their contribution during obesity is unclear. Therefore, the levels of
      regulatory B cells in adipose tissue and peripheral blood samples drawn from
      individuals with overweight, obesity, and normal-weight were evaluated. METHODS:
      The percentages of Breg cells were analyzed by flow cytometry. The activity of
      Breg cells was assessed by measuring the release of IFN-gamma in the supernatants
      of co-cultures of CD4+ T and regulatory B cells with an ELISA assay. The levels
      of IL-17 and IFN-gamma produced by the CD4+ T cells were assessed using an ELISA
      assay. RESULTS: Diminished frequencies of Breg cells with phenotypes
      CD19+CD27+CD38High, CD19+CD24HighCD38High, and CD19+CD24HighCD38HighIL-10+ cells
      were observed in the blood samples from the individuals with overweight and
      obesity but not in the individuals with normal-weight. The production of IFN
      gamma in CD4+ T-cell cultures showed a decrease in the presence of Breg cells in
      individuals with obesity and normal-weight. We found fewer percentages of
      CD19+CD27+CD38High cells in the adipose tissue samples from individuals with
      overweight and obesity compared to individuals with normal-weight. In addition,
      elevated levels of IL-17 and IFN-gamma in the supernatants of the cultures of
      CD4+ T cells from the individuals with obesity compared to the individuals with
      normal-weight were observed. CONCLUSIONS: The results suggest that individuals
      with obesity show increased levels of Th1/Th17 cytokines, which might be caused
      by the decreased frequency of regulatory B cells.

PMID- 30115555
TI  - Defining Adherence to Dietary Self-Monitoring Using a Mobile App: A Narrative
      Review.
AB  - Understanding how adherence to dietary self-monitoring with apps has been defined
      is a first step toward examining the relationship between adherence and weight
      loss. The purpose of this review was to explore how adherence to dietary self
      monitoring has been defined in the empirical literature that addresses weight
      loss app use by overweight and obese adults. The integrative review method and
      the preferred reporting items for systematic reviews and meta-analyses guided
      this review. Scientific databases (n=5) were searched, which yielded 29 studies.
      Studies were screened, evaluated for data quality, and then analyzed according to
      the constant comparison method. Most studies were weak to moderate quality.
      Results indicated that adherence was operationally defined in two ways. Adherence
      was defined as either adherent or nonadherent based on the completion of
      recording a minimum amount of calorie intake or a calorie amount within a
      specific range of calories. Another way that adherence was defined was the
      frequency of dietary self-monitoring, which included the frequency of dietary
      intake recording, interaction with apps, and the timing of recording. Some
      studies defined adherence in both ways. Most included studies lacked diversity in
      study samples. Until a consensus is reached, it may be prudent to study multiple
      indicators of adherence to dietary self-monitoring using apps, and their
      respective relationships with weight loss. Studies are needed that address the
      type and degree of adherence to dietary self-monitoring with an app that is
      associated with weight loss in diverse populations.

PMID- 30115556
TI  - Dietary Assessment with a Wearable Camera among Children: Feasibility and
      Intercoder Reliability.
AB  - BACKGROUND: The eButton, a multisensor device worn on the chest, uses a camera to
      passively capture images of everything in front of the child throughout the day.
      These images can be analyzed to provide a passive method of dietary intake
      assessment. OBJECTIVE: This study assessed the eButton's feasibility and
      intercoder reliability for dietary intake assessment. DESIGN: Children were
      recruited in the summer and fall of 2015, in Houston, TX, to wear the eButton to
      take 2 full days of dietary images, and the child-parent dyad participated in a
      following-day interview to verify what dietitians recorded from the images.
      PARTICIPANTS/SETTING: Thirty 9- to 13-year-old children participated during days
      convenient to them. MAIN OUTCOME MEASURES: Two dietitians independently manually
      reviewed the images to identify eating events, foods in those events, and portion
      sizes. STATISTICAL ANALYSES PERFORMED: Descriptive statistics of agreements and
      disagreements were calculated between dietitians and with children; t tests and
      Bland-Altman plots of differences in total kilocalories were calculated between
      dietitians and between initial dietitian estimates and those finalized after the
      verification interviews. RESULTS: The dietitians agreed on the identity of 60.5%
      of the 1,026 foods but disagreed on 28.6% of the foods and on the names for 10.8%
      of the foods. After the verification interviews, the dietitians agreed with the
      child-parent dyads on the identity of 77.0% of the 921 foods; the child-parent
      dyad identified 12.4% of the day's foods when images were not available or not
      clear; the child-parent dyad clarified that 5.4% of the foods identified were not
      consumed by the child; and the child-parent dyad clarified the identity of 5.2%
      of the foods. A software-based approach (three-dimensional wire mesh) could be
      used to estimate portion size on 24% of the foods, and professional judgment was
      required for 67.8%. Mean caloric intakes per day were not statistically
      significantly different between dietitians but were different between dietitians
      and child-parent dyads in total and on day 2. CONCLUSIONS: An early test of
      intercoder reliability of an all-day image method of dietary intake assessment
      obtained intercoder agreement between the two dietitians processing these images
      of intraclass correlation coefficient=0.67. A following-day verification
      interview with the child and parent was necessary to ensure completeness of
      estimates. Several feasibility problems occurred, which may be remedied with
      additional participant and dietitian training and further technological
      development.

PMID- 30115557
TI  - No Parkin Zone: Mitophagy without Parkin.
AB  - Mitochondria are essential highly dynamic organelles that provide the necessary
      energy for a variety of different processes, such as survival, proliferation, and
      migration. In order to maintain an intact mitochondrial network, cells have
      developed quality control systems that allow the removal of damaged or
      superfluous mitochondria by selective mitochondrial autophagy called mitophagy.
      Although the parkin/PINK1 axis is often considered the main regulator of
      mitophagy, a growing body of evidence has shown that this pathway is not unique
      and that mitophagy can still be functional in the absence of parkin. Here, we
      will review recent literature describing parkin-independent mitophagy and its
      role in various physiopathological conditions, therefore representing potential
      new targets to treat diseases affected by dysregulated mitophagy.

PMID- 30115559
TI  - Unravelment of Medtronic Onyx stent during bifurcation stenting using the jailed
      wire technique; An adverse effect of helical stent structure?
AB  - A 62-year old male underwent treatment of a bifurcation lesion in the left
      anterior descending coronary artery using provisional stenting with a jailed wire
      technique. Severe longitudinal stent deformation and unravelment of the stent
      part proximal of the bifurcation occurred when we tried to pull the jailed wire
      from the side branch. The described case poses a caution on the use of this
      specific stent(-design) in bifurcation lesions.

PMID- 30115560
TI  - Trends in atrial fibrillation and prescription of oral anticoagulants and embolic
      strokes in Germany.
AB  - BACKGROUND: The aim of the study was to compare trends in frequency of atrial
      fibrillation (AF) with the prescription rates of oral anticoagulants (OAC) and
      the incidence of embolic stroke (ES) from 2005 through 2014. METHODS: Annual
      numbers of hospitalized patients with AF and ES were extracted from the Federal
      Bureau of Statistics. Defined daily doses (DDD) of prescribed OAC among
      outpatients were extracted from the insurance drug information system. RESULTS:
      The number of cases hospitalized with the diagnosis AF increased continuously by
      78.3% (1.25 Million in 2005 to 2.19 Million in 2014, p < 0.001), likewise
      frequency of ES increased by 89.0% (from 46,068 to 87,050, p < 0.001) and the
      number of prescribed DDD of OAC almost doubled by 105.4% (from 271,328 to
      557,281, p < 0.001). There is an almost linear correlation between occurrence of
      AF and ES (R2 = 0.9683). In contrast association between prescription rate of OAC
      and incidence of ES is not linear as there was a disproportional increase in OAC
      prescriptions beginning in the year 2010 that is not accompanied by a reduction
      of cases hospitalized with ES. CONCLUSIONS: Our analysis of drug treatment rates
      for OAC in outpatients and hospitalization rates for ES revealed a
      disproportional increase in prescription of OAC beginning in the year 2010 that
      does not affect the number of cases hospitalized with ES.

PMID- 30115558
TI  - Finding the Middle Ground for Autophagic Fusion Requirements.
AB  - Autophagosome/amphisome-lysosome fusion is a highly regulated process at the
      protein, lipid, and biochemical level. Each primary component of fusion, such as
      the core SNAREs, HOPS complex, or physical positioning by microtubule-associated
      dynein motors, are regulated at multiple points to ensure optimum conditions for
      autophagic flux to proceed. With the complexity of the membrane fusion system, it
      is not difficult to imagine how autophagic flux defect-related disorders, such as
      Huntington's disease, non-familial Alzheimer's disease, and Vici syndrome
      develop. Each membrane fusion step is regulated at the protein, lipid, and ion
      level. This review aims to discuss the recent developments toward understanding
      the regulation of autophagosome, amphisome, and lysosome fusion requirements for
      successful autophagic flux.

PMID- 30115563
TI  - Quercetin protects against intestinal barrier disruption and inflammation in
      acute necrotizing pancreatitis through TLR4/MyD88/p38 MAPK and ERS inhibition.
AB  - OBJECTIVE: To investigate the effects of quercetin on intestinal barrier
      disruption and inflammation in acute necrotizing pancreatitis (ANP) in rats, and
      its possible mechanism. METHODS: ANP was established by retrograde injection of
      3.5% sodium taurocholate into the biliopancreatic duct, and quercetin (50 mg/kg *
      3) was administered by intraperitoneal injection prior to and after ANP
      induction. Pancreatitis was assessed by pancreatic histopathology, plasma
      amylase, pancreatic myeloperoxidase (MPO) activity, IL-1beta, TNFalpha and IL-6
      levels. Injury of the distal ileum was assessed by histological evaluation. The
      ultrastructural changes of ileal epithelial cells were examined by transmission
      electron microscope (TEM). Intestinal barrier function was estimated by plasma
      diamine oxidase (DAO), d-lactate, endotoxin; and intestinal tight junction
      proteins including zonula occludens-1 (ZO-1), claudin 1, occludin; and bacterial
      translocation. Intestinal inflammation was determined by IL-1beta, TNFalpha and
      IL-17 A expression. TLR4, MyD88, pp38 MAPK, and endoplasmic reticulum stress
      (ERS)-related molecules (Bip, p-IRE1alpha, sXBP1, p-eIF2alpha, ATF6) were
      measured by immunohistochemistry and WB. RESULTS: Quercetin intervention
      attenuated pancreatic and ileal pathological damages in ANP (P < 0.05),
      ameliorated intestinal barrier disruption and inflammation (P < 0.05). Meantime,
      QE significantly suppressed intestinal TLR4/MyD88/p38 MAPK pathway and ERS
      activation. CONCLUSIONS: Quercetin plays a protective role against intestinal
      barrier disruption and inflammation in ANP, probably partly by inhibiting
      TLR4/MyD88/p38 MAPK and ERS activation.

PMID- 30115562
TI  - Endoscopic ultrasound appearance of pancreatic serotonin-staining neuroendocrine
      neoplasms.
AB  - BACKGROUND/OBJECTIVES: The pancreatic localization of serotonin-staining
      neuroendocrine neoplasms is extremely rare. This is a retrospective study aimed
      at analyzing the endoscopic ultrasound appearance of pancreatic serotoninoma.
      METHODS: Between 2010 and 2016, all consecutive patients with histologically
      proven pancreatic serotoninoma who had undergone endoscopic ultrasound were
      enrolled. RESULTS: Eight patients (six F, median age 68.5 years) had a diagnosis
      of pancreatic serotoninoma and underwent endoscopic ultrasound examinations.
      Median diameter of the lesion was ten mm. The nodule echotexture was hypoechoic
      in seven out of eight cases. The most frequent localization was the pancreatic
      neck (four); in three cases, the tumor was located in the pancreatic head and in
      one in the body. In seven cases the tumor caused a main pancreatic duct dilation;
      in three cases also the secondary ducts were dilated. In one case a dilation of
      the common bile duct was observed. At contrast-enhanced endoscopic ultrasound no
      one showed the typical contrast-enhancement. Elastography (available in two
      patients) showed a rigid pattern of the lesion. CONCLUSIONS: From this case
      series a specific endoscopic ultrasound appearance resulted for pancreatic
      serotoninoma, different from other types of pancreatic neuroendocrine neoplasm,
      but it is difficult to differentiate it from a pancreatic adenocarcinoma or an
      intraductal papillary mucinous neoplasm.

PMID- 30115564
TI  - Physical activity and sedentary behavior thresholds for identifying childhood
      hypertension and its phenotypes: The Healthy Growth Study.
AB  - Hypertension phenotypes may represent differential pathophysiologic mechanisms
      and clinical impact, yet they have been poorly investigated. The study aimed to
      examine the associations of physical activity and sedentary behavior with
      hypertension phenotypes in a large group of Greek children and to identify
      thresholds regarding risk of hypertension. This was a cross-sectional study with
      a regionally representative sample of 2473 schoolchildren aged 9-13 years, with
      full data on physical activity and sedentary behavior indices, as well as
      arterial blood pressure measurements, physical examination, and anthropometry.
      Hypertensive children of both sexes had lower levels of physical activity
      (steps/d). Hypertensive girls had lower moderate-to-vigorous physical activity
      (MVPA), whereas hypertensive boys with isolated systolic hypertension (ISH) had
      more screen time than their normotensive counterparts. Increased levels of
      physical activity was associated with 33%-54% lower risk of all hypertension
      phenotypes in both sexes, whereas increased MVPA was associated with 41%-65%
      lower risk of all phenotypes in girls and with ISH and systolic and diastolic
      hypertension (SDH) in boys. In boys, higher sedentary time was associated with
      11%-13% higher risk for SDH and ISH. Cutoff points of 12,378 steps/d, 47.3 min/d
      of MVPA, and 2.9 h/d of sedentary behavior were determined for identifying
      children at increased risk of hypertension. Physical activity is inversely
      associated with all hypertension phenotypes, whereas sedentary behavior is
      positively associated with ISH and SDH in boys. More studies should confirm the
      hypertension-specific cutoff values identified to be used in future prevention
      programs for childhood hypertension.

PMID- 30115565
TI  - Transmembrane mucin MUC13 distinguishes intraductal papillary mucinous neoplasms
      from non-mucinous cysts and is associated with high-risk lesions.
AB  - BACKGROUND: Intraductal papillary mucinous neoplasms (IPMN) are currently managed
      based on imaging characteristics and cyst fluid sampling. This study was designed
      to determine if MUC13, a glycoprotein aberrantly overexpressed in pancreatic
      adenocarcinoma, might aid in distinguishing high-risk lesions (high grade
      dysplasia/invasive disease) from low-grade lesions. METHODS: MUC13
      immunohistochemical staining was performed on surgically resected formalin-fixed
      tissue specimens from 49 IPMNs and 23 non-mucinous cysts. Membranous MUC13
      expression was measured by H-score, which quantifies staining intensity and the
      percentage of cells involved (range 0-300). RESULTS: MUC13 expression was
      detected in all IPMNs and was significantly greater than in non-mucinous cysts
      (median 210 vs 40, p < 0.001). MUC13 expression was similar among main (n = 26),
      branch (n = 15), and mixed (n = 8) duct lesions (median 210, 200, 225,
      respectively). The highest expression was observed in tumors with intestinal and
      pancreatobiliary histologic features (both median 225) and the lowest in gastric
      type lesions (median 200). MUC13 expression was significantly greater in high
      risk lesions (n = 21) compared to those with low-grade dysplasia (n = 28) (median
      250 vs 195, p < 0.001). CONCLUSION: MUC13 expression was significantly greater in
      high-risk IPMNs in this analysis. The preoperative assessment of MUC13 in cyst
      fluid samples warrants further investigation.

PMID- 30115561
TI  - Gonococcal Defenses against Antimicrobial Activities of Neutrophils.
AB  - Neisseria gonorrhoeae initiates a strong local immune response that is
      characterized by copious recruitment of neutrophils to the site of infection.
      Neutrophils neutralize microbes by mechanisms that include phagocytosis,
      extracellular trap formation, production of reactive oxygen species, and the
      delivery of antimicrobial granular contents. However, neutrophils do not clear
      infection with N. gonorrhoeae. N. gonorrhoeae not only expresses factors that
      defend against neutrophil bactericidal components, but it also manipulates
      neutrophil production and release of these components. In this review, we
      highlight the numerous approaches used by N. gonorrhoeae to survive exposure to
      neutrophils both intracellularly and extracellularly. These approaches reflect
      the exquisite adaptation of N. gonorrhoeae to its obligate human host.

PMID- 30115566
TI  - Identifying Priorities for Faculty Development in General Surgery Using the
      Delphi Consensus Method.
AB  - OBJECTIVE: Faculty teaching skills are critical for effective surgical education,
      however, which skills are most important to be taught in a faculty development
      program have not been well defined. The objective of this study was to identify
      priorities for faculty development as perceived by surgical educators. DESIGN: We
      used a modified Delphi methodology to assess faculty perceptions of the value of
      faculty development activities, best learning modalities, as well as barriers and
      priorities for faculty development. An expert panel developed the initial survey
      and distributed it to the membership of the Association of Program Directors in
      Surgery. Responses were reviewed by the expert panel and condensed to 3 key
      questions that were redistributed to the survey participants for final ranking.
      PARTICIPANTS: Seven experts reviewed responses to 8 questions by 110
      participants. 35 participants determined the final ranking responses to 3 key
      questions. RESULTS: The top three priorities for faculty development were: 1)
      Resident assessment/evaluation and feedback 2) Coaching for faculty teaching, and
      3) Improving intraoperative teaching skills. The top 3 learning modalities were:
      1) Coaching 2) Interactive small group sessions, and 3) Video-based education.
      Barriers to implementing faculty development included time limitations, clinical
      workload, faculty interest, and financial support. CONCLUSIONS: Faculty
      development programs should focus on resident assessment methods, intraoperative
      and general faculty teaching skills using a combination of coaching, small group
      didactic and video-based education. Concerted efforts to recognize and
      financially reward the value of teaching and faculty development is required to
      support these endeavors and improve the learning environment for both residents
      and faculty.

PMID- 30115567
TI  - RNA Polymerase III as a Gatekeeper to Prevent Severe VZV Infections.
AB  - In most individuals, varicella zoster virus (VZV) causes varicella upon primary
      infection and zoster during reactivation. However, in a subset of individuals,
      VZV may cause severe disease, including encephalitis. Host genetics is believed
      to be the main determinant of exacerbated disease manifestations. Recent studies
      have demonstrated that defects in the DNA sensor RNA polymerase III (POL III)
      confer selective increased susceptibility to VZV infection, thus providing
      fundamental new insight into VZV immunity. Here we describe the roles of POL III
      in housekeeping and immune surveillance during VZV infection. We present the
      latest knowledge on the role of POL III in VZV infection and discuss outstanding
      questions related to the role of POL III in VZV immunity, and how this insight
      can be translated into clinical medicine.

PMID- 30115568
TI  - SCCT President's Page: SCCT in 2018 and Beyond.

PMID- 30115569
TI  - Incomplete Cor Triatriatum Dexter: An Unsettling Guest in the Percutaneous
      Closure of Atrial Septal Defects.

PMID- 30115571
TI  - Incidental diagnosis of appendiceal ascariasis during colonoscopy.

PMID- 30115570
TI  - Use of Intra-aortic Balloon Pump as a Bridge to Heart Transplant in Spain:
      Results From the ASIS-TC Study.
AB  - INTRODUCTION AND OBJECTIVES: In Spain, intra-aortic balloon pump (IABP) has been
      used frequently as a bridge to urgent heart transplant (HT). We sought to analyze
      the clinical outcomes of this strategy. METHODS: We conducted a case-by-case,
      retrospective review of clinical records of 281 adult patients listed for urgent
      HT under IABP support in 16 Spanish institutions from 2010 to 2015. Pre- and post
      transplant survival and adverse clinical events were analyzed. RESULTS: A total
      of 194 (69%, 95%CI, 63.3-74.4) patients were transplanted and 20 (7.1%, 95%CI,
      4.4-10.8) died during a mean period of IABP support of 10.9+/-9.7 days. IABP
      support was withdrawn before an organ became available in 32 (11.4%) patients.
      Thirty-five (12.5%, 95%CI, 8.8-16.9) patients transitioned from IABP to full
      support mechanical devices. Mean urgent waiting list time increased from 5.9+/
      6.3 days in 2010 to 15+/-11.7 days in 2015 (P=.001). Post-transplant survival
      rates at 30-days, 1-year, and 5-years were 88.1% (95%CI, 85.7-90.5), 76% (95%CI,
      72.9-79.1), and 67.8% (95%CI, 63.7-71.9), respectively. The incidence rate of
      major adverse clinical outcomes-device dysfunction, stroke, bleeding or infection
      during IABP support was 26 (95%CI, 20.6-32.4) episodes per 1000 patient-days. The
      incidence rate of IABP explantation due to complications was 7.2 (95%CI, 4.5
      10.8) cases per 1000 patient-days. CONCLUSIONS: In a setting of short waiting
      list times, IABP can be used to bridge candidates to urgent HT with acceptable
      postoperative results, but there were significant rates of adverse clinical
      events during support.

PMID- 30115572
TI  - Management of hilum infiltrating tumors of the liver: The impact of experience
      and standardization on outcome.
AB  - BACKGROUND: The primary endpoint of this study was to evaluate the outcome of
      surgery for perihilar cholangiocarcinoma in a high-volume tertiary referral
      center. METHODS: The study population consisted of 196 consecutive patients with
      histologically confirmed perihilar cholangiocarcinoma-PHC-who were candidates to
      surgical treatment. Factors affecting postoperative morbidity were evaluated in
      the whole series (primary endpoint) and after stratification of patients
      according to the following criteria: (a) perioperative management protocol
      implementation; (b) monocentric management (secondary endpoint). RESULTS: The
      postoperative morbidity rate was 51.5% and mortality 4.1%. The most frequent
      cause of death was postoperative liver failure. At multivariate analysis, factors
      affecting the risk of morbidity were: side of hepatectomy, liver volume,
      intraoperative blood loss, preoperative optimization and single-center
      management. Patients treated according to preoperative optimization protocol, as
      well as patients with monocentric management experienced a significant reduction
      of postoperative morbidity. Preoperative optimization and single-center
      management significantly affected even long term outcome of patients. CONCLUSION:
      Despite continuous improvement in the surgical field, hilum-infiltrating tumors
      still remain associated with therapeutic and management challenges: a correct
      preoperative management in a tertiary referral center provides a benefit in terms
      of morbidity and mortality, thus improving long term results.

PMID- 30115573
TI  - Incidence and prevalence of eosinophilic oesophagitis increase continiously in
      adults and children in Central Spain: A 12-year population-based study.
AB  - OBJECTIVES: To update population-based incidence, prevalence and trends for
      eosinophilic oesophagitis (EoE) in children and adults over the past decade.
      METHODS: All patients referred to our EoE unit and living in the study area up to
      December 2017 were prospectively registered. Endoscopy and pathology databases
      and clinical charts were manually reviewed. Diagnosis of EoE was confirmed upon
      symptoms of oesophageal dysfunction and eosinophilia >15 eos/HPF. Annual
      incidence rates and prevalence were estimated with confidence intervals (CI) of
      95%. RESULTS: A total of 117 patients, including 19 children, were diagnosed with
      EoE in the 2006-2017 period. In 2017, the prevalence of EoE in children was 111.9
      (95%CI, 67.4-174.6) cases/100,000 inhabitants and in adults 111.9 (95%CI, 90.8
      136.5) also, and in both cases was significantly higher for male patients. The
      highest prevalences were observed in ages ranging between 20 and 24 and 35-39
      years old. Mean incidence rates of the study period were 10.6 and 9.1 new
      cases/100,000 inhabitants/year in children and adults, respectively. Rise in the
      appearance of EoE during the study period exceeded that for endoscopic
      procedures. No seasonal variation was observed in the diagnosis of EoE.
      CONCLUSION: The incidence and prevalence of EoE has increased sharply in central
      Spain, beyond previous estimations, with one out of every 893 inhabitants now
      being diagnosed.

PMID- 30115574
TI  - Congenital biliary atresia in an infant born to hepatitis B mother treated with
      telbivudine before and during pregnancy.

PMID- 30115575
TI  - Vedolizumab for refractory collagenous colitis: Another piece of the puzzle.

PMID- 30115576
TI  - Aerodynamic Characteristics of Growl Voice and Reinforced Falsetto in Metal
      Singing.
AB  - OBJECTIVES: The present study aimed to assess the aerodynamic characteristics of
      vocally healthy metal singers when producing growl voice or reinforced falsetto.
      METHODS: Fifty-four participants (metal singers) were initially enrolled in this
      study, with 23 meeting the inclusion criteria. Sixteen participants performed
      growl voice and seven performed reinforced falsetto as a voice resource during
      metal singing. All participants were asked to undergo rigid laryngeal
      videostroboscopy to confirm the absence of laryngeal pathology. Then, subjects
      were aerodynamically assessed while performing growl voice or reinforced
      falsetto. RESULTS: Higher glottal airflow rate, sound pressure level, and
      subglottic pressure (Psub) for growl voice samples compared to vowel production
      without growl voice (keeping the same fundamental frequency [F0]) were found.
      Higher Psub, sound pressure level, and glottal resistance for high-pitched
      reinforced falsetto compared to naive falsetto (keeping the same F0) were found.
      No differences for F0 were found for neither growl voice nor reinforced falsetto.
      CONCLUSIONS: It seems that growl voice is produced by decreasing vocal folds
      adduction and increasing Psub, which in turn, promotes an increased airflow rate.
      Reinforced falsetto is characterized by an increased vocal fold adduction and an
      increased Psub. A proper resonance strategy in reinforced falsetto and a
      decreased glottal adduction in growl voice might probably be the factors that
      contribute to prevent voice problems in singers who use these vocal resources,
      classically labeled as vocal abuse.

PMID- 30115577
TI  - Reply to the Letter to the Editor.

PMID- 30115578
TI  - Voice Characteristics of Young Girl Role in Kunqu Opera.
AB  - Three electroglottographic parameters, fundamental frequency, contact quotient,
      and speed quotient were analyzed for two singers of Young girl role in Kunqu
      Opera. Each singer performed three conditions, singing, stage speech, and reading
      lyrics. The phonation types adopted in different conditions were explored based
      on electroglottographic parameters. Fundamental frequency, contact quotient, and
      speed quotient showed different distributions among conditions. Five phonation
      types were used in singing and stage speech, which include (1) breathy voice, (2)
      modal voice with low degree of posterior glottal adduction, (3) modal voice, (4)
      falsetto, and (5) falsetto with high degree of posterior glottal adduction. The
      phonation strategies partly showed differences between singers. Different
      phonation type collocations were employed in singing and stage speech. The
      relationship between phonation types and pitch was complex. The phonation types
      actually used were different from and more complex than those in traditional
      Kunqu Opera singing theory.

PMID- 30115579
TI  - Vocal Characteristics of School-Aged Children With and Without Attention Deficit
      Hyperactivity Disorder.
AB  - OBJECTIVES: The aim of this study was to describe the laryngeal anatomy,
      perceptual, acoustic, and aerodynamic vocal characteristics of school-aged
      children with and without Attention Deficit Hyperactivity Disorder (ADHD). The
      predisposition that children with ADHD have for laryngeal injuries are recurrent
      in nature and are more often than not overlooked as laryngitis. Previous studies
      have reported varied results on the prevalence rates of pediatric vocal fold
      nodules within the school-aged ADHD population. STUDY DESIGN: A static, two-group
      comparison was used in the study to investigate the clinical, perceptual,
      acoustic, and aerodynamic vocal characteristics of children between 7 and 9 years
      old with and without ADHD. METHODS: The study replicated the protocol as executed
      by Barona-Lleo and Fernandez (2016) with additions. The Multidimensional Voice
      Program and the Voice Range Profile as additions to the assessment of vocal
      parameters were used with which comparable dysphonia severity index scores were
      calculated. Once-off clinical, perceptual, acoustic, and aerodynamic voice
      assessments were conducted on 20 age-gender matched participants (Control group
      mean age [months] = 98.80, standard deviation = 10.379; ADHD group mean age
      [months] = 108.00, standard deviation = 10.873). It was hypothesized that
      children with ADHD would have more hyperfunctional vocal characteristics; leading
      to laryngeal injuries, than their control group peers. RESULTS: Forty-five
      percent (n = 9) of the total sample population (both groups combined) had
      laryngeal pathology. Similar parent reported etiological voice symptoms and vocal
      habits were seen across both groups. Both groups performed similarly across both
      perceptual and aerodynamic voice assessments. Acoustically, the control group
      achieved significantly higher producible pitches than the ADHD group (P = 0.028)
      and were found to have more dysphonic dysphonia severity index scores than their
      ADHD group peers (P = 0.034). CONCLUSION: Prepubertal, school-aged children with
      or without ADHD may have similar vocal characteristics than previously thought.
      This is in support of the null hypothesis. The authors of the current study
      recommend that vocal screening in all school-aged children be carried out as an
      effective measure to monitor voice disorders in the pediatric population. Future
      research into larger sample sizes with this population with a special focus on
      the effect that central nervous system stimulants may have on the voice is
      recommended.

PMID- 30115580
TI  - Prevalence and predictors of liver fibrosis evaluated by vibration controlled
      transient elastography in type 1 Gaucher disease.
AB  - BACKGROUND & AIMS: Long-term liver-related complications of Gaucher disease (GD)
      include cirrhosis, portal hypertension and hepatocellular carcinoma. Although
      liver fibrosis is the main determinant of adverse liver-related clinical
      outcomes, it has rarely been evaluated in previously published cohorts of GD
      patients. We aimed at: assessing the prevalence of significant liver fibrosis in
      a cohort of patients with type 1 GD; identifying its predictors among GD-related
      variables, enzyme replacement therapy (ERT) and metabolic features. METHODS: 37
      adult type 1 GD patients from two Italian academic referral centers were
      prospectively submitted to vibration controlled transient elastography
      (Fibroscan(r)); significant fibrosis was defined as liver stiffness >=7 kPa.
      RESULTS: Median liver stiffness was 4.6 [3-15.1] kPa and 7 patients (19%) had
      significant fibrosis. Significant fibrosis was associated with splenectomy (p =
      .046) and with scores (DS3: p = .002; SSI: p = .026) and biomarkers (ACE: p =
      .016; HDL cholesterol: p = .004) of GD severity. Length of ERT was significantly
      lower in GD patients with significant fibrosis. In the subgroup of 29 patients
      who were on stable ERT for at least 24 months, further to splenectomy, GD
      severity and non-N370S GBA1 genotypes, also diastolic blood pressure, BMI and the
      number of metabolic syndrome (MetS) components emerged as factors significantly
      associated with significant fibrosis. CONCLUSIONS: Significant fibrosis is
      present in a remarkable proportion of adult type 1 GD patients. Splenectomy, GD
      severity and GBA1 genotypes are major GD-related predictors of liver fibrosis.
      Length of ERT is inversely correlated with liver disease in GD patients,
      suggesting a beneficial effect of ERT on liver fibrosis. However, GD patients on
      stable ERT should be monitored for metabolic complications, since MetS features
      may enhance liver disease progression despite optimal GD control.

PMID- 30115581
TI  - Opinion of a group of patients about health professionals with tattoos.
AB  - OBJECTIVE: To learn the opinion of a group of young patients about health
      personnel with tattoos. METHOD: Descriptive study conducted in the first semester
      of 2017 on patients admitted to the Obstetrics Unit of the Hospital Complex of
      Ourense. The data collection was carried out by means of a self-administered
      questionnaire prepared "in-house" where several photographs of health
      professionals with and without tattoos were shown. A descriptive analysis of the
      variables and nonparametric tests were carried out to determine the potential
      association between the variables, using the statistical package SPSS 15.0(r).
      RESULTS: A total of 66 patients participated. Regardless of whether or not the
      study participants had tattoos themselves, they all scored the non-tattooed
      better than the tattooed health professionals, although these differences were
      less in the participants who had tattoos. No significant data were found in any
      of the cases. CONCLUSIONS: The participants of our study scored tattooed health
      professionals more poorly in terms of their professionalism, credibility,
      closeness and involvement compared to their counterparts without tattoos.

PMID- 30115582
TI  - 'Understanding Disability': Evaluating a contact-based approach to enhancing
      attitudes and disability literacy of medical students.
AB  - BACKGROUND: Health disparities and disparities in the provision of healthcare to
      people with disabilities remains a topic of concern. Research demonstrates that
      attitudes of healthcare providers contribute to this disparity. The approach to
      disability education and training in medical school warrants evaluation.
      OBJECTIVES: This study sought to investigate the efficacy of an educational
      intervention in cultivating positive attitudes towards disability in medical
      students, and determine the specific impact of an interaction-based hospital
      visit to patients undergoing neurological rehabilitation. METHODS: Web-based
      questionnaires were distributed to medical students undertaking a 12-week
      'Understanding Disability' module. Measures of anxiety, attitude, competency and
      empathy were obtained from 65 students at the beginning (T1), middle (T2) and end
      (T3) of the module. At T2, approximately half of the students had completed a
      hospital visit and half had not. RESULTS: Scores changed significantly across all
      constructs between the beginning and end of the module suggesting a positive
      overall module effect. Findings confirmed a significant difference in anxiety and
      empathy levels between the group of students who had completed the visit to the
      rehabilitation hospital by the middle survey wave and those who had not,
      indicating a specific placement effect. CONCLUSIONS: Our findings suggest that
      interpersonal contact with individuals with disabilities has a distinct impact on
      the affective variables of anxiety and empathy. Previous research suggests that
      this contributes towards improved attitudes to disability. Overall, we provide
      strong evidence for the inclusion of contact-based educational interventions in
      medical school to enhance students' attitudes to disability.

PMID- 30115583
TI  - Racial and ethnic differences in post-stroke subjective cognitive decline exist.
AB  - BACKGROUND: Racial and ethnic minorities consistently demonstrate disparate post
      stroke outcomes. However, there is a paucity of literature related to whether
      this disparity exists specifically in post-stroke cognitive decline. OBJECTIVE:
      To determine if racial and ethnic disparities exist in post-stroke subjective
      cognitive decline (SCD) among non-Hispanic Blacks (Blacks), American Indians or
      Alaska Natives (AI/ANs), Hispanics, and non-Hispanic Whites (Whites) in the
      United States using data from the Behavioral Risk Factor Surveillance System
      (BRFSS). METHODS: A retrospective analysis was completed using the 2016 BRFSS
      data in adults who self-reported stroke and SCD. Descriptive statistics were
      completed for baseline comparisons using chi squared tests for categorical
      variables. A binary logistic regression controlling for baseline differences was
      completed to examine racial and ethnic differences in SCD. RESULTS: Significant
      differences in SCD were identified across all racial and ethnic groups. When
      compared to Whites, Blacks, AI/ANs, and Hispanics more frequently reported
      worsening confusion or memory loss that interfered with day-to-day activities and
      the ability to work, volunteer, and engage in social activities outside of the
      home. AI/ANs who reported SCD were more likely than Whites to have help
      available. Hispanic persons with SCD or their family members were most likely to
      discuss SCD with a healthcare provider. CONCLUSION: Although persons from all
      racial and ethnic groups in this study experienced some degree of SCD, Blacks,
      AI/ANs, and Hispanics most frequently reported worsening confusion or memory loss
      impacting engagement in day-to-day activities and the ability to work, volunteer,
      and engage in social activities outside of the home.

PMID- 30115584
TI  - Pilot randomized trial of a telephone-delivered physical activity and weight
      management intervention for individuals with lower extremity amputation.
AB  - BACKGROUND: Obesity and inactivity are common and burdensome for people with
      lower extremity amputation (LEA). The extent to which home-based physical
      activity/weight management programs are effective and safe for people with LEA is
      unknown. Translating effective interventions for understudied disability groups
      is needed. OBJECTIVE: To test the feasibility, acceptability, and safety of a
      weight management and physical activity intervention and obtain preliminary
      efficacy estimates for changes in weight, body composition, and physical
      functioning. METHODS: Eligibility criteria included: LEA >=1 year prior, 18-69
      years of age, overweight or obese and living in the Seattle area. The
      intervention arm received self-monitoring tools (e.g., pedometer, scale) and
      written materials, a single exercise counseling home visit by a physical
      therapist, and up to 11 telephone calls from a health coach over 20 weeks that
      involved motivational interviewing to set specific, attainable, and measurable
      goals. The self-directed control group received the same tools and materials but
      no home visit or coaching calls. RESULTS: Nineteen individuals consented to
      participate, 15 were randomized (mean age = 56, 73% male, 80% transtibial
      amputation) and 11 completed 20-week follow-up assessments. The intervention was
      acceptable and safe. Coached participants had greater decreases in waist
      circumference (mean difference between groups over 20 weeks, baseline values
      carried forward: -4.3 cm, 95% CI -8.2, -0.4, p = 0.03) and fat mass (-2.1 kg, 95%
      CI -3.8, -0.4, p = 0.02). CONCLUSIONS: The home-based intervention was promising
      in terms of efficacy, safety and acceptability. Inclusion of multiple trial
      centers and increased use of technology may facilitate recruitment and retention.

PMID- 30115585
TI  - C190A knockdown mutation in sodium channel domain II of pyrethroid-resistant
      Rhipicephalus appendiculatus.
AB  - This study investigated the target site mutations in the partial sequence of
      voltage-sensitive sodium channel (VSSC) domain II of synthetic pyrethroid (SP)
      resistant Rhipicephalus appendiculatus. Genomic DNA was extracted from seven tick
      populations (two susceptible and five resistant) collected from central, eastern
      and southwestern Uganda. The PCR amplicons of the VSSC domain II were cloned and
      sequenced to determine novel single nucleotide polymorphisms (SNP). A non
      synonymous mutation C78 A corresponding to C190 A was found in all the five SP
      resistant ticks. The C78 A mutation led to amino acid substitution from leucine
      to isoleucine (L21I) which was previously reported to confer knockdown (kdr)
      mutation in R. (Boophilus) microplus. The genetic confirmation of SP-resistant R.
      appendiculatus in central and southwestern Uganda calls for an urgent strategy
      for controlling the ticks.

PMID- 30115586
TI  - Surgical and oncological outcomes of our first 59 cases of robotic
      pancreaticoduodenectomy.
AB  - PURPOSE: Robotics has shown encouraging results for a number of technically
      demanding abdominal surgeries including pancreaticoduodenectomy, which has
      originally represented a relative contraindication to the application of the
      minimally-invasive technique. We aimed to investigate the perioperative,
      clinicopathologic, and oncological outcomes of robot-assisted
      pancreaticoduodenectomy by assessing a consecutive series of totally robotic
      procedures. METHODS: All consecutive patients who underwent robotic
      pancreaticoduodenectomy were included in the present analysis. Perioperative,
      clinicopathologic and oncological outcomes were examined. In order to investigate
      the role of the learning curve, surgical outcomes were also used to compare the
      early and the late phase of our experience. RESULTS: A total of 59 patients
      underwent surgery. Median hospital stay was 9 days (5 - 110), with an overall
      morbidity and mortality of 37% and 3%, respectively. Of note, the rate of
      clinically relevant pancreatic fistula was 11.8%. R0 resections were achieved in
      96% of patients and the 3-year disease-free and overall survivals were 37.2 and
      61.9%, respectively. Overall, surgical outcomes did not vary significantly
      between the first and the late phase of the series. CONCLUSIONS: Robotic
      pancreaticoduodenectomy can be performed competently. It satisfies all features
      of oncological adequacy and may offer a number of advantages over standard
      procedures in terms of surgical results.

PMID- 30115587
TI  - The role of excessive body weight and meniscal instability in the progression of
      osteoarthritis in a rat model.
AB  - BACKGROUND: The main objective of the study was to determine if excessive body
      weight and meniscal destabilization cause knee articular cartilage damage and
      changes in meniscal histology indicative of knee osteoarthritis (OA). METHODS:
      Forty female Lewis rats were randomly assigned to regular diet sham surgery,
      regular diet medial meniscus destabilization (DMM) surgery, high-fat diet sham
      surgery, or high-fat diet DMM surgery. Surgical intervention occurred four weeks
      after diet initiation. Rats were sacrificed four weeks post-surgery. Progression
      of OA was evaluated in femoral condyles and tibial plateaus using the
      Osteoarthritis Research Society International (OARSI) scoring system by two
      blinded scorers. Ossification of menisci was evaluated with digitized
      histological slides using a grid. RESULTS: DMM surgery had greater OARSI scores
      than sham surgery for all knee surfaces in both diet groups (all P < 0.004). The
      high-fat diet sham surgery group had greater OARSI scores than the regular diet
      sham surgery group on all knee surfaces (all P < 0.02). Histological evaluation
      showed the lateral meniscus had more bone than the medial meniscus, but there was
      no relationship between diet or surgery groups and amount of bone in the
      meniscus. CONCLUSIONS: Results suggested excessive body weight may contribute to
      spontaneous onset of OA and emphasized the importance of preventative care in
      those at risk of developing OA.

PMID- 30115588
TI  - Arthroscopic treatment for symptomatic lateral discoid meniscus: The effects of
      different ages, groups and procedures on surgical outcomes.
AB  - BACKGROUND: There is a paucity of literature regarding the results of
      arthroscopic saucerization, with or without stabilization, for lateral discoid
      meniscus (LDM) in children, and differences in clinical outcomes between adults
      and children. The purpose of this study was to compare the clinical outcomes
      following arthroscopic treatment of symptomatic LDM in children versus adults.
      Secondly, outcomes of different surgical procedures (saucerization only and
      saucerization with repair or centralization) were also compared. METHODS: Fifty
      two consecutive patients with LDM were evaluated and divided into two groups.
      Group 1 had 16 patients (18 knees; nine males, seven females) aged <13 years;
      Group 2 had 36 patients (38 knees; 19 males, 17 females) aged >=13 years. All
      patients were arthroscopically treated with saucerization only, or saucerization
      with repair or centralization for LDM. They had a mean follow-up of 30 months
      (range 24-72). Clinical outcomes were compared preoperatively and at final follow
      up (minimum two years) after surgery using patient-reported outcome scores,
      International Knee Documentation Committee (IKDC) scores, and Lysholm scores.
      Radiographic evaluation was also performed for degenerative changes using
      Kellgren-Lawrence classification. RESULTS: The IKDC scores at final follow-up in
      Group 1 demonstrated better clinical outcomes when compared with those in Group 2
      (91.1 +/- 9.49 vs. 73.7 +/- 16.4, P = 0.001). No significant intergroup
      difference was noted at the follow-up for radiographic osteoarthritic grade
      according to Kellgren-Lawrence classification. Similarly, no differences were
      found at final follow-up between saucerization only and saucerization with repair
      or centralization. There were no significant differences in IKDC score of repair
      and centralization at final follow-up. CONCLUSIONS: Clinical outcomes in children
      aged <13 years was significantly better than those aged >=13 years. Arthroscopic
      saucerization only or saucerization with repair or centralization for discoid
      meniscus was effective in improving knee function and preventing early
      degenerative changes during short-term follow-up periods.

PMID- 30115589
TI  - A study of the relationship between meniscal injury and bone microarchitecture in
      ACL reconstructed knees.
AB  - BACKGROUND: Anterior cruciate ligament (ACL) tears increase the risk of
      developing knee osteoarthritis. This risk increases further with concurrent
      meniscus injury. The role of bone changes during knee osteoarthritis development
      are not well-understood, but may be important to its etiology. PURPOSE: To
      explore the effects of ACL tears on bone mineral density (BMD) and bone
      microarchitecture at five years post-op and their relationship to meniscal
      pathology, using high-resolution peripheral quantitative computed tomography (HR
      pQCT). METHODS: Twenty-eight participants with unilateral ACL reconstructions
      five years prior and no evidence of clinical or radiographic osteoarthritis were
      recruited. All participants represented one of three meniscus statuses: meniscus
      intact, meniscus repair, or meniscectomy. BMD and bone microarchitecture of the
      subchondral bone plate and adjacent trabecular bone were assessed using HR-pQCT,
      and percent-differences between the injured and contralateral knee were
      determined. RESULTS: Subchondral bone plate thickness in the lateral femoral
      condyle was higher in the reconstructed knee (9.0%, p = 0.002), driven by the
      meniscus repair and meniscectomy groups (15.2% to 15.4%, p < 0.05). Trabecular
      BMD was lower in the reconstructed knee in the medial femoral condyle (-4.8% to 
      7.6%, p < 0.05), driven by all meniscus statuses. In the lateral compartments,
      few differences in trabecular bone were found. However, accounting for meniscus
      status, the meniscus intact group had lower trabecular BMD throughout both femur
      and tibia. CONCLUSIONS: Five years post-op, reconstructed knees demonstrated
      detectable differences in BMD and bone microarchitecture, despite having normal
      radiographs. Meniscus damage affected primarily the lateral compartment,
      warranting further investigation to determine if these changes relate to
      osteoarthritis development.

PMID- 30115590
TI  - Influence of tibial component rotation on short-term clinical outcomes in Oxford
      mobile-bearing unicompartmental knee arthroplasty.
AB  - BACKGROUND: Malposition of tibial components is an important factor for
      complications in unicompartmental knee arthroplasty (UKA), but the direct
      relationship between clinical outcomes and position of tibial component remains
      unknown. We aimed to investigate whether tibial component rotation in the axial
      plane could affect clinical outcomes after UKA. METHODS: A total of 50 patients
      with anteromedial osteoarthritis of the knee underwent Oxford mobile-bearing UKA
      in this study. Patient-derived clinical scores using the Oxford Knee Score (OKS)
      and the functional activities of Knee Society Score (KSSF) were assessed
      preoperatively, and then after one year and two years following surgery.
      Postoperative tibial component rotation angles using two reference lines in the
      axial plane were assessed using three-dimensional computed tomography two weeks
      postoperatively. External rotation of the tibial component relative to each
      reference line was considered a positive value. We analysed the sequential change
      of the OKS and KSSF using repeated measures analysis of variance (P < 0.05). The
      effects of tibial component rotation on the OKS and KSSF were analysed using
      linear regression analysis. RESULTS: OKS and KSSF showed significant recovery
      between the preoperative and one-year postoperative period. Rotation angles of
      tibial components had significant negative correlations with the recovery of the
      OKS in the two years following UKA. CONCLUSIONS: Tibial component rotation played
      an important role in improving clinical outcomes during the two years following
      Oxford mobile-bearing UKA. A trend towards poor outcome was observed when the
      tibial component was placed at a higher angle of external rotation. LEVEL OF
      EVIDENCE: III.

PMID- 30115591
TI  - Single-leg vertical jump test as a functional test after anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: The aim of this study was to identify the correlations between the
      single-leg vertical jump (SLVJ) test and subjective and objective tests which
      were used widely for determining return-to-sports (RTS) after anterior cruciate
      ligament reconstruction (ACLR). METHODS: Seventy-five patients (29.5 +/- 9.2
      years) who underwent ACLR between May 2012 and Jan 2014 were included. Subjective
      knee scoring systems including subjective International Knee Documentation
      Committee (IKDC) score, Lysholm score, Tegner activity scale, and ACL-Return to
      Sports after Injury (ACL-RSI) scale were assessed. Objective tests were also
      performed. RESULTS: The limb symmetry index (LSI) for SLVJ test and single-leg
      hop for distance (SLHD) test was 89.4 +/- 14.9% and 90.7 +/- 11.7%. LSI for SLVJ
      test was correlated to subjective IKDC scores (r = 0.26, P = 0.024), Tegner
      activity scale (r = 0.64, P < 0.001), ACL-RSI scale (r = 0.61, P < 0.001), LSI
      for SLHD (r = 0.45, P < 0.001), Co-contraction (r = -0.57, P < 0.001), Shuttle
      run (r = -0.52, P < 0.001), and Carioca (r = -0.54, P < 0.001) tests. In
      isokinetic strength tests, extensor peak torque (r = 0.30, P = 0.009) and
      extensor strength deficit (r = -0.41, P < 0.001) were correlated with LSI for
      SLVJ test. CONCLUSION: There were considerable correlations between SLVJ test and
      subjective IKDC scores, Tegner activity scale, ACL-RSI scale, isokinetic extensor
      muscle strength, and all other functional tests. SLVJ test could be used
      conveniently to determine RTS after ACLR in outpatient clinics. LEVEL OF
      EVIDENCE: Level IV, case series.

PMID- 30115592
TI  - Influence of patient-related factors on clinical outcome of tibial tubercle
      transfer combined with medial patellofemoral ligament reconstruction.
AB  - BACKGROUND: Tibial tubercle transfer is frequently used for treating patellar
      instability. This study aimed to analyze the clinical results following tibial
      tuberosity transfer with medial patellofemoral ligament (MPFL) reconstruction in
      the treatment of patellar instability. METHODS: Seventy-two cases presenting a
      lateralized tibial tubercle were treated with tibial tuberosity transfer and MPFL
      reconstruction. Pre-operative and postoperative pain levels and knee function
      were evaluated using common scoring systems. Cartilage status was assessed at the
      time of surgery, and the influence of patient-related factors was analyzed.
      Median and interquartile ranges were used to present the results. RESULTS: After
      a mean of 27.6 (12 -76) months, a re-dislocation rate of 4.2% and significant
      improvement in knee function from a median of 48.0 (33 -70) to 83.0 (68 -94) and
      a median of 44.0 (24 -62) to 85.0 (69 -93), based on Kujala (P <= 0.001) and
      Lysholm (P <= 0.001) scores were observed. The Tegner score significantly
      increased from a median of 3.0 (2 -4) to 4.0 (4 -5) (P <= 0.001), while the pain
      level decreased from a median of 5.0 (3 -8) to 2.0 (0 -3) (P <= 0.001). Cartilage
      lesions were found in 55/72 (76.4%) knees. The likelihood of finding II degrees 
      cartilage lesions was six times higher in cases of >= two previous operations.
      CONCLUSION: Tibial tuberosity transfer with MPFL reconstruction allowed reliable
      patellar stabilization with a low re-dislocation rate. Patient age and
      unsuccessful attempts at surgical stabilization posed significant risk factors
      for cartilage lesions and may have limited postopertive outcomes.

PMID- 30115594
TI  - Bevacizumab therapy for recurrent gliomas: another disappointment?

PMID- 30115593
TI  - Bevacizumab and temozolomide in patients with first recurrence of WHO grade II
      and III glioma, without 1p/19q co-deletion (TAVAREC): a randomised controlled
      phase 2 EORTC trial.
AB  - BACKGROUND: Bevacizumab is frequently used in the treatment of recurrent WHO
      grade II and III glioma, but without supporting evidence from randomised trials.
      Therefore, we assessed the use of bevacizumab in patients with first recurrence
      of grade II or III glioma who did not have 1p/19q co-deletion. METHODS: The
      TAVAREC trial was a randomised, open-label phase 2 trial done at 32 centres
      across Europe in patients with locally diagnosed grade II or III glioma without
      1p/19q co-deletion, with a first and contrast-enhancing recurrence after initial
      radiotherapy or chemotherapy, or both. Previous chemotherapy must have been
      stopped at least 6 months before enrolment and radiotherapy must have been
      stopped at least 3 months before enrolment. Random group assignment was done
      electronically through the European Organisation for Research and Treatment of
      Cancer web-based system, stratified by a minimisation procedure using
      institution, initial histology (WHO grade II vs III), WHO performance status (0
      or 1 vs 2), and previous treatment (radiotherapy, chemotherapy, or both).
      Patients were assigned to receive either temozolomide (150-200 mg/m2, orally)
      monotherapy on days 1-5 every 4 weeks for a maximum of 12 cycles, or the same
      temozolomide regimen in combination with bevacizumab (10 mg/kg, intravenously)
      every 2 weeks until progression. The primary endpoint was overall survival at 12
      months in the per-protocol population. Safety analyses were done in all patients
      who started their allocated treatment. The study is registered at EudraCT (2009
      017422-39) and ClinicalTrials.gov (NCT01164189), and is complete. FINDINGS:
      Between Feb 8, 2011, and July 31, 2015, 155 patients were enrolled and randomly
      assigned to receive either monotherapy (n=77) or combination therapy (n=78).
      Overall survival in the per-protocol population at 12 months was achieved by 44
      (61% [80% CI 53-69]) of 72 patients in the temozolomide group and 38 (55% [47
      69]) of 69 in the combination group. The most frequent toxicity was
      haematological: 17 (23%) of 75 patients in the monotherapy group and 25 (33%) of
      76 in the combination group developed grade 3 or 4 haematological toxicity. Other
      than haematological toxicities, the most common adverse events were nervous
      system disorders (59 [79%] of 75 patients in the monotherapy group vs 65 [86%] of
      76 in the combination group), fatigue (53 [70%] vs 61 [80%]), and nausea (39
      [52%] vs 43 [56%]). Infections were more frequently reported in the combination
      group (29 [38%] of 76 patients) than in the monotherapy group (17 [23%] of 75).
      One treatment-related death was reported in the combination group (infection
      after intratumoral haemorrhage during a treatment-related grade 4
      thrombocytopenia). INTERPRETATION: We found no evidence of improved overall
      survival with bevacizumab and temozolomide combination treatment versus
      temozolomide monotherapy. The findings from this study provide no support for
      further phase 3 studies on the role of bevacizumab in this disease. FUNDING:
      Roche Pharmaceuticals.

PMID- 30115595
TI  - Venetoclax in chronic lymphocytic leukaemia: a possible cure?

PMID- 30115597
TI  - Rapid remission of first-episode schizophrenia with standardised treatment.

PMID- 30115596
TI  - Bendamustine followed by obinutuzumab and venetoclax in chronic lymphocytic
      leukaemia (CLL2-BAG): primary endpoint analysis of a multicentre, open-label,
      phase 2 trial.
AB  - BACKGROUND: Targeted agents such as the type II anti-CD20 antibody obinutuzumab
      and the B-cell lymphoma-2 antagonist venetoclax have shown impressive therapeutic
      activity in chronic lymphocytic leukaemia. The CLL2-BAG trial was initiated to
      investigate the combination of these two agents in patients with chronic
      lymphocytic leukaemia. METHODS: In this ongoing multicentre, open-label,
      investigator-initiated phase 2 trial, patients (aged >=18 years) with chronic
      lymphocytic leukaemia requiring treatment according to the 2008 International
      Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and an Eastern
      Cooperative Oncology Group performance status of 0-2 were enrolled at 16 sites in
      Germany. Patients with a relevant tumour load (absolute lymphocyte count >=25 000
      cells per MUL or lymph nodes with a diameter of >=5 cm) received sequential
      treatment of debulking with two cycles of bendamustine (70 mg/m2 intravenously on
      days 1 and 2 of each of the two 28-day cycles), followed by induction and
      maintenance with obinutuzumab (1000 mg intravenously on days 1-2, 8, and 15 of
      the first induction cycle, every 4 weeks in induction cycles 2-6, and every 12
      weeks in the maintenance phase) and oral venetoclax (starting in induction cycle
      2 with 20 mg/day, with a weekly dose escalation over 5 weeks to the target dose
      of 400 mg/day). The primary endpoint was the proportion of patients achieving an
      overall response by investigator assessment at the end of induction treatment.
      All patients who received at least two induction cycles were included in the
      efficacy analyses and all patients who received at least one dose of study drug
      were included in the safety analyses. This study is registered with
      ClinicalTrials.gov, number NCT02401503. FINDINGS: Between May 6, 2015, and Jan 4,
      2016, 66 patients were enrolled (35 treatment naive and 31 with relapsed or
      refractory disease), three of whom were excluded from the efficacy analysis
      because they received fewer than two induction cycles. Of the remaining 63
      patients in the efficacy-evaluable population, 34 patients (54%) were treatment
      naive and 29 (46%) had relapsed or refractory disease. At data cutoff (Feb 28,
      2017), all patients had completed induction treatment. At the end of the
      induction, 60 (95%) of 63 patients (95% CI 87-99) had responded, including all 34
      patients in the treatment-naive cohort and 26 [90%] of 29 relapsed or refractory
      patients. The most common grade 3-4 adverse events during debulking were
      neutropenia and anaemia (five [11%] of 47 patients each), and thrombocytopenia
      and infection (three [6%] each). The most common grade 3-4 adverse events during
      induction were neutropenia (29 [44%] of 66 patients), infection (nine [14%]),
      thrombocytopenia (eight [12%]), infusion-related reactions (five [8%]), and
      secondary primary malignancy (four [6%]). 89 serious adverse events, including 69
      related to study treatment, were reported. These serious adverse events were also
      mainly infections (four cases in four patients during debulking and 18 cases in
      11 patients during induction) and cytopenia (four cases in four patients during
      debulking and ten cases in seven patients in induction). Five relapsed or
      refractory patients died: three cases of sepsis were deemed related to study
      treatment, whereas two deaths from Richter's transformation were not.
      INTERPRETATION: The sequential application of bendamustine and obinutuzumab
      combined with venetoclax caused no unexpected or cumulative toxicities. The high
      proportion of patients who achieved overall responses, both treatment-naive and
      relapsed or refractory patients irrespective of physical fitness and genetic risk
      factors, compare favourably to established chronic lymphocytic leukaemia
      therapies. Further follow-up will help to define whether the remissions with
      eradication of minimal residual disease achieved with this combination are
      durable after treatment discontinuation. FUNDING: F Hoffmann-La Roche and AbbVie.

PMID- 30115599
TI  - Glycaemic variability in diabetes: clinical and therapeutic implications.
AB  - Glycaemic variability is an integral component of glucose homoeostasis. Although
      it has not yet been definitively confirmed as an independent risk factor for
      diabetes complications, glycaemic variability can represent the presence of
      excess glycaemic excursions and, consequently, the risk of hyperglycaemia or
      hypoglycaemia. Glycaemic variability is currently defined by a large and
      increasing number of metrics, representing either short-term (within-day and
      between-day variability) or long-term glycaemic variability, which is usually
      based on serial measurements of HbA1c or other measures of glycaemia over a
      longer period of time. In this Review, we discuss recent evidence examining the
      association between glycaemic variability and diabetes-related complications, as
      well as non-pharmacological and pharmacological strategies currently available to
      address this challenging aspect of diabetes management.

PMID- 30115600
TI  - Depressive symptoms and suicidality among individuals with epilepsy enrolled in
      self-management studies: Results from the US Centers for Disease Control and
      Prevention Managing Epilepsy Well (MEW) Network.
AB  - Depression is a common comorbidity in people with epilepsy (PWE) that negatively
      affects self-management and a variety of health outcomes. Suicidal ideation is
      also more common among PWE than the general population. We examined correlates of
      depressive symptoms and suicidal ideation in adults using pooled data from
      epilepsy self-management studies conducted by sites in the Centers for Disease
      Control and Prevention (CDC) Research Center's Managing Epilepsy Well (MEW)
      Network that assessed depression severity with the 9-item Patient Health
      Questionnaire (PHQ-9). Of the 770 subjects in the analysis (mean age 42.4 +/-
      13.0 years), the mean total PHQ-9 score was 9.4 +/- 6.6 and 334 subjects (43.4%)
      had moderate to severe depressive symptoms (PHQ-9 >= 10). Only ongoing seizures
      and low education were associated with moderate-severe depressive symptoms in
      multiple logistic regression analysis. Suicidality (PHQ-9, item 9 score >= 1) was
      endorsed by 155 subjects (20.1%). Only nonsuicidal depressive symptoms were
      associated with suicidality in multiple variable logistic regression analysis. We
      show in this large and regionally diverse dataset that both depression and
      suicidal ideation are common among PWE enrolled in self-management studies.
      Future studies are needed to examine whether suicidality exists independently of
      other depressive symptoms in some populations with epilepsy and investigate other
      correlates of suicidality that may inform screening practices.

PMID- 30115598
TI  - Amisulpride and olanzapine followed by open-label treatment with clozapine in
      first-episode schizophrenia and schizophreniform disorder (OPTiMiSE): a three
      phase switching study.
AB  - BACKGROUND: No established treatment algorithm exists for patients with
      schizophrenia. Whether switching antipsychotics or early use of clozapine
      improves outcome in (first-episode) schizophrenia is unknown. METHODS: This three
      phase study was done in 27 centres, consisting of general hospitals and
      psychiatric specialty clinics, in 14 European countries and Israel. Patients aged
      18-40 years who met criteria of the DSM-IV for schizophrenia, schizophreniform
      disorder, or schizoaffective disorder were treated for 4 weeks with up to 800
      mg/day amisulpride orally in an open-label design (phase 1). Patients who did not
      meet symptomatic remission criteria at 4 weeks were randomly assigned to continue
      amisulpride or switch to olanzapine (<=20 mg/day) during a 6-week double-blind
      phase, with patients and staff masked to treatment allocation (phase 2).
      Randomisation was done online by a randomisation website; the application
      implemented stratification by site and sex, and applied the minimisation method
      for randomisation. Patients who were not in remission at 10 weeks were given
      clozapine (<=900 mg/day) for an additional 12 weeks in an open-label design
      (phase 3). The primary outcome was the number of patients who achieved
      symptomatic remission at the final visits of phases 1, 2, and 3, measured by
      intention-to-treat analysis. Data were analysed with a generalised linear mixed
      model, with a logistic link and binomial error distribution. This trial is
      registered with ClinicalTrials.gov, number NCT01248195, and closed to accrual.
      FINDINGS: Between May 26, 2011, and May 15, 2016, we recruited 481 participants
      who signed informed consent. Of the 446 patients in the intention-to-treat
      sample, 371 (83%) completed open-label amisulpride treatment, and 250 (56%)
      achieved remission after phase 1. 93 patients who were not in remission continued
      to the 6-week double-blind switching trial, with 72 (77%) patients completing the
      trial (39 on olanzapine and 33 on amisulpride); 15 (45%) patients on amisulpride
      versus 17 (44%) on olanzapine achieved remission (p=0.87). Of the 40 patients who
      were not in remission after 10 weeks of treatment, 28 (70%) started on clozapine;
      18 (64%) patients completed the 12-week treatment, and five (28%) achieved
      remission. The number of serious adverse events did not differ between the
      treatment arms in phase 2: one patient on olanzapine was admitted to hospital
      because of an epileptic seizure, and one patient on amisulpride was admitted to
      hospital twice because of exacerbations of psychotic symptoms. Over the course of
      the trial, two serious suicide attempts were reported. INTERPRETATION: For most
      patients in the early stages of schizophrenia, symptomatic remission can be
      achieved using a simple treatment algorithm comprising the sequential
      administration of amisulpride and clozapine. Since switching to olanzapine did
      not improve outcome, clozapine should be used after patients fail a single
      antipsychotic trial-not until two antipsychotics have been tried, as is the
      current recommendation. FUNDING: European Commission Seventh Framework Program.

PMID- 30115601
TI  - Negative effects of interictal spikes on theta rhythm in human temporal lobe
      epilepsy.
AB  - Interictal spike is a biomarker of epilepsy that can occur frequently between
      seizures. Its potential effects on brain oscillations, especially on theta rhythm
      (4-8 Hz) that is related to a variety of cognitive processes, remain
      controversial. Using local field potentials recorded from patients with temporal
      lobe epilepsy (TLE), we investigated here the impact of spikes on theta rhythm
      immediately after spikes and during the prolonged periods (lasting 4-36 s)
      between adjacent spikes. Local field potentials (LFPs) were recorded in different
      epileptogenic areas including the anterior hippocampus (aH) and the entorhinal
      cortex (EC) as well as in the extended propagation pathway. We found that
      interictal spikes had a significant inhibitory effect on theta rhythm. Power of
      theta rhythm was reduced immediately after spikes, and the inhibitory effect on
      theta rhythm might sustain during the prolonged between-spike periods. The
      inhibitory effect was more severe when the epileptogenic areas involved both the
      aH and EC compared to that involved only a single structure. These observations
      suggest that interictal spikes have a significant negative impact on theta rhythm
      and may thus play a role in theta-related cognition changes in patients with TLE.

PMID- 30115602
TI  - "Ictal epileptic headache" and the revised International Headache Classification
      (ICHD-3) published in Cephalalgia 2018, vol. 38(1) 1-211: Not just a matter of
      definition!

PMID- 30115603
TI  - Brain network alterations of mesial temporal lobe epilepsy with cognitive
      dysfunction following anterior temporal lobectomy.
AB  - The aims of this study were to investigate the brain network connectivity
      alterations of intractable unilateral mesial temporal lobe epilepsy (MTLE) with
      cognitive dysfunction before and after anterior temporal lobectomy (ATL) using
      resting-state functional magnetic resonance imaging (rs-fMRI) study and to
      further observe the correlation between the brain network connectivity with
      cognitive performance. Fourteen patients with unilateral left MTLE before and
      after ATL were compared with thirty healthy controls (HCs) on functional
      connectivity (FC) between resting-state networks (RSNs). The correlation between
      the neuropsychological tests of patients and abnormal FC was further
      investigated. When compared with the HCs, patients before surgery showed
      significantly changed FC between special RSNs. No difference of FC was found
      between each RSN when patients were compared with the HCs after surgery. Compared
      with patients before surgery, patients after surgery showed significantly
      decreased FC between RSNs. Abnormal FC between RSNs significantly correlated with
      Montreal Cognitive Assessment (MoCA) scores. Our study suggested that dynamic
      alterations of RSN after ATL in unilateral MTLE may be closely related with
      seizure generating. However, unchanged FC between RSN before and after ATL may be
      closely related with cognitive performance. The present findings may help us
      understand the feature of brain network alterations in patients with left MTLE
      who became seizure-free following ATL.

PMID- 30115604
TI  - Sodium cromoglycate reduces short- and long-term consequences of status
      epilepticus in rats.
AB  - Several studies indicate that sodium cromoglycate (CG) induces neuroprotective
      effects in acute neurological conditions. The present study focused on
      investigating if the use of CG in rats during the post-status epilepticus (post
      SE) period reduces the acute and long-term consequences of seizure activity. Our
      results revealed that animals that received a single dose of CG (50 mg/kg s.c.:
      subcutaneously) during the post-SE period showed a lower number of neurons in the
      process of dying in the dentate gyrus, hilus, cornu ammonis 1 (CA1), and CA3 of
      the dorsal hippocampus than the rats that received the vehicle. However, this
      effect was not evident in layers V-VI of the sensorimotor cortex or the lateral
      posterior thalamic nucleus. A second experiment showed that animals that received
      CG subchronically (50 mg/kg s.c. every 12 h for 5 days followed by 24 mg/kg/day
      s.c. for 14 days using osmotic minipumps) after SE presented fewer generalized
      convulsive seizures and less neuronal damage in the lateral-posterior thalamic
      nucleus but not in the hippocampus or cortex. Our data indicate that CG can be
      used as a therapeutic strategy to reduce short- and long-term neuronal damage in
      the hippocampus and thalamus, respectively. The data also indicate that CG can
      reduce the expression of generalized convulsive spontaneous seizures when it is
      given during the latent period of epileptogenesis.

PMID- 30115605
TI  - Executive and behavioral functioning in pediatric frontal lobe epilepsy.
AB  - OBJECTIVE: Epilepsy, as a chronic and neurological disease, is generally
      associated with an increased risk for social and emotional behavior problems in
      children. These findings are mostly derived from studies on children with
      different epilepsy types. However, there is limited information about the
      associations between frontal lobe epilepsy (FLE) and cognitive and behavioral
      problems. The aim of this study was to examine relationships between FLE and
      executive and behavioral functioning reported by parents and teachers. MATERIAL
      AND METHODS: Teachers and parents of 32 children (18 boys, 14 girls, mean age 9;
      2 years +/-1;6) with a confirmed diagnosis of FLE completed the Behavioral Rating
      Inventory of Executive Function (BRIEF), the Child Behavior Checklist (CBCL), and
      Teacher Report Form (TRF). RESULTS: About 25 to 35% of the parents and teachers
      rated children in the abnormal range of the main scales of the BRIEF, CBCL, and
      TRF. Teachers tend to report more metacognition problems, whereas parents tend to
      report more behavior regulation problems. Children with left-sided FLE showed
      more problems than children with bilateral or right-sided FLE. The whole range of
      executive dysfunctioning is linked to behavioral dysfunctioning in FLE, but
      ratings vary across settings and informants. The epilepsy variables age of onset,
      lateralization, drug load, and duration of epilepsy had only a small and
      scattered contribution. CONCLUSION: Ratings on the BRIEF, CBCL, and TRF are
      moderately to highly correlated, suggesting a (strong) link between executive and
      behavioral functioning. Subtle differences between parents and teachers ratings
      suggest different executive function demands in various settings.

PMID- 30115606
TI  - Harmonized Genome Wide Typing of Tubercle Bacilli Using a Web-Based Gene-By-Gene
      Nomenclature System.
AB  - BACKGROUND: Global tuberculosis (TB) control is challenged by uncontrolled
      transmission of Mycobacterium tuberculosis complex (Mtbc) strains, esp. of
      multidrug (MDR) or extensively resistant (XDR) variants. Precise analysis of
      transmission networks is the basis to trace outbreak M/XDR clones and improve TB
      control. However, classical genotyping tools lack discriminatory power due to the
      high similarity of strains of particular successful lineages, e.g. Beijing or
      outbreak strains. This can be overcome by whole genome sequencing (WGS)
      approaches, but these are not yet standardized to facilitate larger
      investigations encompassing different laboratories or outbreak tracing across
      borders. METHODS: We established and improved a whole genome gene-by-gene multi
      locus sequence typing approach encompassing a stable set of core genome genes
      (cgMLST) and linked it to a web-based nomenclature server (cgMLST.org)
      facilitating assignment and storage of allele numbers. FINDINGS: We evaluated and
      refined a previously suggested cgMLST schema by using a reference strain set (n =
      251) reflecting the global diversity of the Mtbc. A set of 2891 genes showed
      excellent performance with at least 97% of the genes reliably identified in
      strains of all Mtbc lineages and in discriminating outbreak strains. cgMLST
      allele numbers were automatically retrieved from and stored at cgMLST.org.
      INTERPRETATION: The refined cgMLST schema provides high resolution genome-based
      typing of clinical strains of all Mtbc lineages. Combined with a web-based
      nomenclature server, it facilitates rapid, high-resolution, and harmonized
      tracing of clinical Mtbc strains needed for prospective local and global
      surveillance.

PMID- 30115608
TI  - Glutathione S-transferase omega gene polymorphism as a biomarker for human
      papilloma virus and cervical cancer in Iranian women
AB  - Objective: Human papillomavirus (HPV) infection is an important sexually
      transmitted infection worldwide. Persistent infections with different high-risk
      HPV genotypes may cause cervical intraepithelial neoplasia and cervical cancer.
      Single nucleotide polymorphisms of glutathione S-transferase omega (GSTO) 1 and 2
      play an important role in cancer progression. To evaluate GSTO gene polymorphism
      influence on women's susceptibility to low-risk or high-risk HPV infections and
      also risk of cervical cancer development. Material and Methods: We examined 50
      patients with cervical cancer, 43 patients who were positive for HPV, and 43
      healthy individuals as negative controls. We used polymerase chain reaction
      restriction fragment length polymorphism to determine GSTO1 A140D and GSTO2 N142D
      variants in study participants. Results: We found a significant association
      between the GSTO1 A140D gene polymorphism and HPV 6, 16, 18, 16/18 infections and
      cervical cancer in Iranian women. We noted a significant difference for the
      140AD/142NN combination genotype between patients in the cervical cancer group
      and healthy controls. There were no significant differences for the GSTO2 N142D
      genotype and allele frequencies between the patient (i.e., cervical cancer and
      HPV-positive) groups and controls. Conclusion: The 140AD genotype, 140D allele,
      and 140AD/142NN combination genotype seem to confer a protective property in
      women's susceptibility to HPV 6, 16, 18, 16/18 infections and cervical cancer.
      However, the GSTO2 N142D polymorphism is not associated with HPV infections and
      cervical cancer. It would appear that GSTO1 A140D SNPs likely play a role in the
      level of susceptibility to HPV-related cervical cancer.

PMID- 30115609
TI  - Congenital central nervous system anomalies: the 10-year single center experience
      on a challenging issue in perinatal medicine.
AB  - OBJECTIVE: Our goal is to highlight the prenatal diagnosis and management of
      central nervous system (CNS) anomalies through sharing our clinic's experience.
      MATERIAL AND METHODS: We evaluated prenatal findings and postnatal outcomes of
      neonates who had a CNS anomaly diagnosis in our clinic over a ten-year period. A
      total of 183 cases with various CNS anomalies were included in the study. Birth
      or termination preferences of mothers were recorded in all cases, and postnatal
      diagnosis concordance and prognosis after surgical procedures were evaluated in
      mothers who chose to continue the pregnancy. RESULTS: The mean maternal age was
      28.2+/-5.5 years, mean gravida was 2.2+/-1.3, and the mean gestational age at
      diagnosis was 30.5+/-5.5 weeks. Seventy five out of 183 (41%) patients chose to
      terminate their pregnancy. Twenty babies (26.6%) in the termination of pregnancy
      group had additional anomalies. A hundred and eight patients gave birth at our
      institution. Mean birth weight was 3060+/-647.5 g, mean gestational week at
      delivery was 37.9+/-1.7 weeks, and mean APGAR score (5th minute) was 8.8+/-2.3.
      Four neonates died at the postpartum first day. The postnatal diagnosis of 60 of
      the 108 (55.5%) patients who gave birth was concordant with the prenatal
      diagnosis, and 32 of the 108 (29.6%) babies underwent surgical interventions.
      CONCLUSION: CNS anomalies have broad spectrum and variable prognoses. This study
      highlights the limitations of prenatal diagnoses, and the need for parents to
      have this information in order to determine the course of their pregnancy and
      prepare themselves for the postnatal challenging treatment/rehabilitation
      process.

PMID- 30115611
TI  - Seven days in medicine: 8-14 August 2018.

PMID- 30115607
TI  - Non-lab and semi-lab algorithms for screening undiagnosed diabetes: A cross
      sectional study.
AB  - BACKGROUND: The terrifying undiagnosed rate and high prevalence of diabetes have
      become a public emergency. A high efficiency and cost-effective early recognition
      method is urgently needed. We aimed to generate innovative, user-friendly
      nomograms that can be applied for diabetes screening in different ethnic groups
      in China using the non-lab or noninvasive semi-lab data. METHODS: This
      multicenter, multi-ethnic, population-based, cross-sectional study was conducted
      in eight sites in China by enrolling subjects aged 20-70. Sociodemographic and
      anthropometric characteristics were collected. Blood and urine samples were
      obtained 2 h following a standard 75 g glucose solution. In the final analysis,
      10,794 participants were included and randomized into model development (n =
      8096) and model validation (n = 2698) group with a ratio of 3:1. Nomograms were
      developed by the stepwise binary logistic regression. The nomograms were
      validated internally by a bootstrap sampling method in the model development set
      and externally in the model validation set. The area under the receiver operating
      characteristic curve (AUC) was used to assess the screening performance of the
      nomograms. Decision curve analysis was applied to calculate the net benefit of
      the screening model. RESULTS: The overall prevalence of undiagnosed diabetes was
      9.8% (1059/10794) according to ADA criteria. The non-lab model revealed that
      gender, age, body mass index, waist circumference, hypertension, ethnicities,
      vegetable daily consumption and family history of diabetes were independent risk
      factors for diabetes. By adding 2 h post meal glycosuria qualitative to the non
      lab model, the semi-lab model showed an improved Akaike information criterion
      (AIC: 4506 to 3580). The AUC of the semi-lab model was statistically larger than
      the non-lab model (0.868 vs 0.763, P < 0.001). The optimal cutoff probability in
      semi-lab and non-lab nomograms were 0.088 and 0.098, respectively. The
      sensitivity and specificity were 76.3% and 81.6%, respectively in semi-lab
      nomogram, and 72.1% and 67.3% in non-lab nomogram at the optimal cut off point.
      The decision curve analysis also revealed a bigger decrease of avoidable OGTT
      test (52 per 100 subjects) in the semi-lab model compared to the non-lab model
      (36 per 100 subjects) and the existed New Chinese Diabetes Risk Score (NCDRS, 35
      per 100 subjects). CONCLUSION: The non-lab and semi-lab nomograms appear to be
      reliable tools for diabetes screening, especially in developing countries.
      However, the semi-lab model outperformed the non-lab model and NCDRS prediction
      systems and might be worth being adopted as decision support in diabetes
      screening in China.

PMID- 30115612
TI  - Nuclear magnetic resonance-based metabolomics in respiratory medicine.

PMID- 30115610
TI  - Developing Embedded Taxonomy and Mining Patients' Interests From Web-Based
      Physician Reviews: Mixed-Methods Approach.
AB  - BACKGROUND: Web-based physician reviews are invaluable gold mines that merit
      further investigation. Although many studies have explored the text information
      of physician reviews, very few have focused on developing a systematic topic
      taxonomy embedded in physician reviews. The first step toward mining physician
      reviews is to determine how the natural structure or dimensions is embedded in
      reviews. Therefore, it is relevant to develop the topic taxonomy rigorously and
      systematically. OBJECTIVE: This study aims to develop a hierarchical topic
      taxonomy to uncover the latent structure of physician reviews and illustrate its
      application for mining patients' interests based on the proposed taxonomy and
      algorithm. METHODS: Data comprised 122,716 physician reviews, including reviews
      of 8501 doctors from a leading physician review website in China (haodf.com),
      collected between 2007 and 2015. Mixed methods, including a literature review,
      data-driven-based topic discovery, and human annotation were used to develop the
      physician review topic taxonomy. RESULTS: The identified taxonomy included 3
      domains or high-level categories and 9 subtopics or low-level categories. The
      physician-related domain included the categories of medical ethics, medical
      competence, communication skills, medical advice, and prescriptions. The patient
      related domain included the categories of the patient profile, symptoms,
      diagnosis, and pathogenesis. The system-related domain included the categories of
      financing and operation process. The F-measure of the proposed classification
      algorithm reached 0.816 on average. Symptoms (Cohen d=1.58, Deltau=0.216,
      t=229.75, and P<.001) are more often mentioned by patients with acute diseases,
      whereas communication skills (Cohen d=-0.29, Deltau=-0.038, t=-42.01, and
      P<.001), financing (Cohen d=-0.68, Deltau=-0.098, t=-99.26, and P<.001), and
      diagnosis and pathogenesis (Cohen d=-0.55, Deltau=-0.078, t=-80.09, and P<.001)
      are more often mentioned by patients with chronic diseases. Patients with mild
      diseases were more interested in medical ethics (Cohen d=0.25, Deltau 0.039,
      t=8.33, and P<.001), operation process (Cohen d=0.57, Deltau 0.060, t=18.75, and
      P<.001), patient profile (Cohen d=1.19, Deltau 0.132, t=39.33, and P<.001), and
      symptoms (Cohen d=1.91, Deltau=0.274, t=62.82, and P<.001). Meanwhile, patients
      with serious diseases were more interested in medical competence (Cohen d=-0.99,
      Deltau=-0.165, t=-32.58, and P<.001), medical advice and prescription (Cohen d=
      0.65, Deltau=-0.082, t=-21.45, and P<.001), financing (Cohen d=-0.26, Deltau=
      0.018, t=-8.45, and P<.001), and diagnosis and pathogenesis (Cohen d=-1.55,
      Deltau=-0.229, t=-50.93, and P<.001). CONCLUSIONS: This mixed-methods approach,
      integrating literature reviews, data-driven topic discovery, and human
      annotation, is an effective and rigorous way to develop a physician review topic
      taxonomy. The proposed algorithm based on Labeled-Latent Dirichlet Allocation can
      achieve impressive classification results for mining patients' interests.
      Furthermore, the mining results reveal marked differences in patients' interests
      across different disease types, socioeconomic development levels, and hospital
      levels.

PMID- 30115613
TI  - The mode of action of anticholinergics in asthma.
AB  - Acetylcholine binds to muscarinic receptors to play a key role in the
      pathophysiology of asthma, leading to bronchoconstriction, increased mucus
      secretion, inflammation and airway remodelling. Anticholinergics are muscarinic
      receptor antagonists that are used in the treatment of chronic obstructive
      pulmonary disease and asthma. Recent in vivo and in vitro data have increased our
      understanding of how acetylcholine contributes to the disease manifestations of
      asthma, as well as elucidating the mechanism of action of anticholinergics. This
      review assesses the latest literature on acetylcholine in asthma pathophysiology,
      with a closer look at its role in airway inflammation and remodelling. New
      insights into the mechanism of action of anticholinergics, their effects on
      airway remodelling, and a review of the efficacy and safety of long-acting
      anticholinergics in asthma treatment will also be covered, including a summary of
      the latest clinical trial data.

PMID- 30115615
TI  - Reducing the need for carbon dioxide monitoring in the investigation of
      paediatric sleep disordered breathing.

PMID- 30115616
TI  - Metabolic rates, swimming capabilities, thermal niche and stress response of the
      lumpfish, Cyclopterus lumpus.
AB  - The lumpfish (Cyclopterus lumpus) is a semi-pelagic globiform teleost native to
      the North Atlantic with a ventral suction disc that allows for attachment onto
      surfaces. Some local populations are in decline and the species has recently
      become important in salmonid sea cages as cleaner fish. Little is known about the
      basal physiology of the lumpfish, and a characterization of thermal performance,
      aerobic capacity, swimming behaviour and stress response is therefore warranted.
      In the present study, swim tunnel respirometry was performed on lumpfish
      acclimated to 3, 9 or 15 degrees C. Higher temperatures were also attempted, but
      at 18 degrees C their behaviour became erratic and 15% of the fish died over 3
      weeks of acclimation. Water current tolerance was assessed in two size classes
      (~75 g and ~300 g) both with and without the ability to voluntarily use the
      ventral suction disc. Lastly, blood samples were taken from resting, exhausted
      and recovered fish to assess haematological effects of exercise stress. Lumpfish
      had relatively low aerobic scopes that increased slightly with temperature.
      Critical swimming speed was poor, increasing within the tested temperatures from
      1.3 to 1.7 body lengths s-1 in 300 g fish. They struggled to remain sucked onto
      surfaces at currents above 70-110 cm s-1, depending on size. Acute stress effects
      were modest or non-existent in terms of changes in cortisol, lactate, glucose,
      erythrocytes and ion balance. These results describe a typical sluggish and
      benthic species, which is contradictory to the pelagic nature of lumpfish in
      large parts of its lifecycle.

PMID- 30115614
TI  - Extensively drug-resistant tuberculosis in South Africa: genomic evidence
      supporting transmission in communities.
AB  - Despite evidence that transmission is driving an extensively drug-resistant TB
      (XDR-TB) epidemic, our understanding of where and between whom transmission
      occurs is limited. We sought to determine whether there was genomic evidence of
      transmission between individuals without an epidemiologic connection.We conducted
      a prospective study of XDR-TB patients in KwaZulu-Natal, South Africa, during the
      2011-2014 period. We collected sociodemographic and clinical data, and identified
      epidemiologic links based on person-to-person or hospital-based connections. We
      performed whole-genome sequencing (WGS) on the Mycobacterium tuberculosis
      isolates and determined pairwise single nucleotide polymorphism (SNP)
      differences.Among 404 participants, 123 (30%) had person-to-person or hospital
      based links, leaving 281 (70%) epidemiologically unlinked. The median SNP
      difference between participants with person-to-person and hospital-based links
      was 10 (interquartile range (IQR) 8-24) and 16 (IQR 10-23), respectively. The
      median SNP difference between unlinked participants and their closest genomic
      link was 5 (IQR 3-9) and half of unlinked participants were within 7 SNPs of at
      least five participants.The majority of epidemiologically-unlinked XDR-TB
      patients had low pairwise SNP differences with at least one other participant,
      consistent with transmission. These data suggest that much of transmission may
      result from casual contact in community settings between individuals not known to
      one another.

PMID- 30115619
TI  - Palliativedrugs.com.

PMID- 30115617
TI  - Drosophila mef2 is essential for normal mushroom body and wing development.
AB  - MEF2 (myocyte enhancer factor 2) transcription factors are found in the brain and
      muscle of insects and vertebrates and are essential for the differentiation of
      multiple cell types. We show that in the fruit fly Drosophila, MEF2 is essential
      for the formation of mushroom bodies in the embryonic brain and for the normal
      development of wings in the adult. In embryos mutant for mef2, there is a
      striking reduction in the number of mushroom body neurons and their axon bundles
      are not detectable. The onset of MEF2 expression in neurons of the mushroom
      bodies coincides with their formation in the embryo and, in larvae, expression is
      restricted to post-mitotic neurons. In flies with a mef2 point mutation that
      disrupts nuclear localization, we find that MEF2 is restricted to a subset of
      Kenyon cells that project to the alpha/beta, and gamma axonal lobes of the
      mushroom bodies, but not to those forming the alpha'/beta' lobes.

PMID- 30115620
TI  - Palliative care integration in haematological malignancies: towards a needs-based
      approach.

PMID- 30115621
TI  - Social media in palliative medicine research: jump into the cool water.

PMID- 30115622
TI  - Towards evidence-based medicine for paediatricians.

PMID- 30115624
TI  - "No deal" Brexit could be catastrophic for NHS, warns BMA.

PMID- 30115618
TI  - The small G protein Arl8 contributes to lysosomal function and long-range axonal
      transport in Drosophila.
AB  - The small GTPase Arl8 has emerged as a major regulatory GTPase on lysosomes.
      Studies in mammalian cells have shown that it regulates both fusion with late
      endosomes and also lysosomal motility. In its active GTP-bound state, it recruits
      to lysosomes the HOPS (homotypic fusion and protein sorting) endosomal tethering
      complex and also proteins that link lysosomes to microtubule motors such as the
      kinesin adaptor PLEKHM2. To gain further insights into Arl8 biology, we examined
      the single Drosophila ortholog. Drosophila Arl8 is essential for viability, and
      mitotic clones of mutant cells are able to continue to divide but show
      perturbation of the late endocytic pathway. Progeny-lacking Arl8 die as late
      larvae with movement-paralysis characteristic of defects in neuronal function.
      This phenotype was rescued by expression of Arl8 in motor neurons. Examination of
      these neurons in the mutant larvae revealed smaller synapses and axons with
      elevated levels of carriers containing synaptic components. Affinity
      chromatography revealed binding of Drosophila Arl8 to the HOPS complex, and to
      the Drosophila ortholog of RILP, a protein that, in mammals, recruits dynein to
      late endosomes, with dynein being known to be required for neuronal transport.
      Thus Drosophila Arl8 controls late endocytic function and transport via at least
      two distinct effectors.This article has an associated First Person interview with
      the first author of the paper.

PMID- 30115625
TI  - Children's intensive care units are failing to monitor breathing adequately.

PMID- 30115627
TI  - Catastrophic stroke in a patient with left ventricular non-compaction.
AB  - : SummaryWe present the case of a 32-year-old man who presented with a remote
      history of chest pain and was diagnosed with non-compaction cardiomyopathy on
      echocardiography. On presentation, he was relatively asymptomatic with normal
      cardiac function. Unfortunately, he presented 1 year later with a catastrophic
      embolic stroke. LEARNING POINTS: Left ventricular non-compaction (LVNC) is a
      myocardial disorder characterised by prominent left ventricular (LV) trabeculae,
      a thin compacted layer and deep intertrabecular recesses.Two-dimensional
      echocardiography with colour Doppler is the study of choice for diagnosis and
      follow-up of LVNC. CMR serves an important role where adequate echocardiographic
      imaging cannot be obtained.LVNC is associated with high rates of mortality and
      morbidity in adults, including heart failure, thromboembolic events and
      tachyarrhythmias.

PMID- 30115628
TI  - European drug agency loses 30% of staff in planned move to Amsterdam.

PMID- 30115629
TI  - CDK4/6 Inhibitors: What Is the Best Cocktail?
AB  - CDK4/6 inhibitors have shown great potential in the new armamentarium against
      cancer. However, their effect as single agents is limited, and the hopes are on
      new combinatory strategies. Recent data suggest that inhibiting mTOR may
      significantly cooperate with cell-cycle arrest in a variety of cancers. Clin
      Cancer Res; 1-3. (c)2018 AACR. See related article by Song et al.

PMID- 30115626
TI  - Geometrical confinement controls the asymmetric patterning of brachyury in
      cultures of pluripotent cells.
AB  - Diffusible signals are known to orchestrate patterning during embryogenesis, yet
      diffusion is sensitive to noise. The fact that embryogenesis is remarkably robust
      suggests that additional layers of regulation reinforce patterning. Here, we
      demonstrate that geometrical confinement orchestrates the spatial organisation of
      initially randomly positioned subpopulations of spontaneously differentiating
      mouse embryonic stem cells. We use micropatterning in combination with
      pharmacological manipulations and quantitative imaging to dissociate the multiple
      effects of geometry. We show that the positioning of a pre-streak-like population
      marked by brachyury (T) is decoupled from the size of its population, and that
      breaking radial symmetry of patterns imposes polarised patterning. We provide
      evidence for a model in which the overall level of diffusible signals together
      with the history of the cell culture define the number of T+ cells, whereas
      geometrical constraints guide patterning in a multi-step process involving a
      differential response of the cells to multicellular spatial organisation. Our
      work provides a framework for investigating robustness of patterning and provides
      insights into how to guide symmetry-breaking events in aggregates of pluripotent
      cells.

PMID- 30115630
TI  - Proteomic Discovery and Validation of the Confounding Effect of Heparin
      Administration on the Analysis of Candidate Cardiovascular Biomarkers.
AB  - BACKGROUND: Several plasma proteins have been suggested as markers for a variety
      of cardiovascular conditions but fail to qualify in independent patient cohorts.
      This may relate to interference of medication on plasma protein concentrations.
      We used proteomics to identify plasma proteins that changed in concentration with
      heparin administration and therefore potentially may confound their evaluation as
      biomarkers in situations in which heparin is used. METHODS: We used a proteomic
      approach based on isobaric tagging and nano-LC-MS/MS analysis to quantify several
      hundred proteins in a discovery study in which individual plasma samples from 9
      patients at intravascular ultrasound follow-up 12 months after an acute
      myocardial infarction before heparin administration and 2, 15, and 60 min after
      heparin administration; we validated our findings in 500 individual plasma
      samples obtained at admission from patients with suspected ST segment elevation
      myocardial infarction (STEMI), of whom 363 were treated with heparin before
      admission. RESULTS: In the discovery study, 25 of 653 identified plasma proteins
      displayed a changed concentration after heparin administration (Bonferroni
      corrected P value at P < 7.66 * 10-5). Fourteen of the proteins changed
      significantly among heparin-treated patients in the validation study (nominal
      significance level of P < 6.92 * 10-5). Among heparin-affected proteins in both
      the discovery study and the validation study were midkine, spondin 1, secreted
      frizzled-like protein 1, lipoprotein lipase, and follistatin, all previously
      associated with STEMI. CONCLUSIONS: Medications such as heparin administration
      given before blood sampling may confound biomarker discovery and should be
      carefully considered in such studies.

PMID- 30115632
TI  - Benefits and risks of JAK inhibition.

PMID- 30115633
TI  - Non-zero-sum game of transfusions: EOL in leukemia.

PMID- 30115635
TI  - Primary cutaneous small/medium CD4+ T-cell lymphoproliferative disorder.

PMID- 30115634
TI  - Moving target PF4 directs HIT responses.

PMID- 30115631
TI  - TCF3 alternative splicing controlled by hnRNP H/F regulates E-cadherin expression
      and hESC pluripotency.
AB  - Alternative splicing (AS) plays important roles in embryonic stem cell (ESC)
      differentiation. In this study, we first identified transcripts that display
      specific AS patterns in pluripotent human ESCs (hESCs) relative to differentiated
      cells. One of these encodes T-cell factor 3 (TCF3), a transcription factor that
      plays important roles in ESC differentiation. AS creates two TCF3 isoforms, E12
      and E47, and we identified two related splicing factors, heterogeneous nuclear
      ribonucleoproteins (hnRNPs) H1 and F (hnRNP H/F), that regulate TCF3 splicing. We
      found that hnRNP H/F levels are high in hESCs, leading to high E12 expression,
      but decrease during differentiation, switching splicing to produce elevated E47
      levels. Importantly, hnRNP H/F knockdown not only recapitulated the switch in
      TCF3 AS but also destabilized hESC colonies and induced differentiation.
      Providing an explanation for this, we show that expression of known TCF3 target E
      cadherin, critical for maintaining ESC pluripotency, is repressed by E47 but not
      by E12.

PMID- 30115636
TI  - Harlequin cells.

PMID- 30115637
TI  - Exflagellation of Plasmodium vivax microgametocytes in human peripheral blood.

PMID- 30115638
TI  - Cord blood transplantation and refractory severe anaplastic anemia.

PMID- 30115640
TI  - The endoderm from a diverse perspective.
AB  - The historic town of Taos, New Mexico, with its rich multicultural history of art
      and craft, was the site of the second Keystone Symposium on 'Endoderm Development
      and Disease', which was held in February 2018. The theme of the meeting was
      'Cross-Organ Comparison and Interplay', emphasizing an integrative and
      multisystem approach to the broad topics of organ physiology, homeostasis,
      repair, regeneration and disease. As we review here, participants shared their
      recent discoveries and discussed how new technologies developed in one organ
      system might be applied to answer crucial questions in another. Other integrative
      themes were how agents such as parasites, microbes, immune cells, physical forces
      and innervation can affect tissue organization and progenitor cell dynamics, and
      how defects in the development of an organ can impact its adult function.
      Participants came away with a broader vision of their field and a renewed sense
      of collective energy empowered by novel tools and fresh ideas.

PMID- 30115639
TI  - The adverse health effects and harms related to marijuana use: an overview
      review.
AB  - BACKGROUND: With impending marijuana legislation in Canada, a broad understanding
      of the harms associated with marijuana use is needed to inform the clinical
      community and public, and to support evidence-informed public policy development.
      The purpose of the review was to synthesize the evidence on adverse health
      effects and harms of marijuana use. METHODS: We searched MEDLINE, The Cochrane
      Database of Systematic Reviews, Embase, PsycINFO, the Cumulative Index to Nursing
      and Allied Health Literature, and the Health Technology Assessment Database from
      the inception of each database to May 2018. Given that systematic reviews
      evaluating one or other specific harm have been published, this is an overview
      review with the primary objective of assessing a health effect or harm. Data on
      author, country and year of publication, search strategy and results, and
      outcomes were extracted. Quality was assessed using the AMSTAR (A Measurement
      Tool to Assess Systematic Reviews) checklist. RESULTS: The final analysis
      included 68 reviews. Evidence of harm was reported in 62 reviews for several
      mental health disorders, brain changes, cognitive outcomes, pregnancy outcomes
      and testicular cancer. Inconclusive evidence was found for 20 outcomes (some
      mental health outcomes, other types of cancers and all-cause mortality). No
      evidence of harm was reported for 6 outcomes. INTERPRETATION: Harm was associated
      with most outcomes assessed. These results should be viewed with concern by
      physicians and policy-makers given the prevalence of use, the persistent
      reporting of a lack of recognition of marijuana as a possibly harmful substance
      and the emerging context of legalization for recreational use.

PMID- 30115643
TI  - Microfluidic Cell Culture Platforms to Capture Hepatic Physiology and Complex
      Cellular Interactions.
AB  - Animal models such as rats and primates provide body-wide information for drug
      and metabolite responses, including organ-specific toxicity and any unforeseen
      side effects on other organs. Although effective in the drug-screening process,
      their translatability to humans is limited because of the lack of high
      concordance and correlation among enzymatic mechanisms, cellular mechanisms, and
      resulting toxicities. A significant mode of failure for safety prediction in drug
      screening is hepatotoxicity, resulting in ~30% of all safety-related drug
      failures and withdrawals from the market. The liver is a multifunctional organ
      with diverse metabolic, secretory, and inflammatory response roles and is
      essential for maintaining key body functions. Conventional cell culture platforms
      (such as multiwell plate cultures) and metabolic enzyme systems (microsomes,
      cytochrome P450 enzymes) have been routinely used to assess drug pharmacokinetics
      and metabolism. However, current in vitro models often fail to recapitulate the
      complexity and dynamic nature of human tissues, imposing a heavy reliance on in
      vivo testing using preclinical species that have metabolic processes, disease
      mechanisms, and modes of toxicity distinct from humans. Recently,
      microphysiological systems (MPS) have gained attention as powerful tools with the
      potential to generate human-relevant information that can supplant and fill the
      gap of knowledge between preclinical animal models and simpler, conventional in
      vitro cell culture systems. Developments in microfabrication technologies for
      generating complex microfluidic systems, along with the ability to establish and
      maintain multicellular models to capture dynamic, human-relevant behavior, have
      provided new avenues to generate such physiologically relevant systems. These MPS
      platforms, when designed and developed with in vivo-derived design parameters,
      have the potential to capture key aspects and better mimic organ functionality.
      In this review, we discuss developments in microtechnologies for fabricating,
      establishing, and maintaining hepatic cell culture systems, with a specific focus
      on models that aim to capture in vivo physiology in vitro. By designing
      microscale systems to impart specific in vivo physiologic parameters, it is
      possible to create a dynamic system that can capture multiple aspects of the
      hepatic microenvironment, bringing us closer to a comprehensive in vitro testing
      platform for hepatic responses and toxicities.

PMID- 30115641
TI  - Activation of MYC, a bona fide client of HSP90, contributes to intrinsic
      ibrutinib resistance in mantle cell lymphoma.
AB  - The BTK inhibitor ibrutinib has demonstrated a remarkable therapeutic effect in
      mantle cell lymphoma (MCL). However, approximately one-third of patients do not
      respond to the drug initially. To identify the mechanisms underlying primary
      ibrutinib resistance in MCL, we analyzed the transcriptome changes in ibrutinib
      sensitive and ibrutinib-resistant cell lines on ibrutinib treatment. We found
      that MYC gene signature was suppressed by ibrutinib in sensitive but not
      resistant cell lines. We demonstrated that MYC gene was structurally abnormal and
      MYC protein was overexpressed in MCL cells. Further, MYC knockdown with RNA
      interference inhibited cell growth in ibrutinib-sensitive as well as ibrutinib
      resistant cells. We explored the possibility of inhibiting MYC through HSP90
      inhibition. The chaperon protein is overexpressed in both cell lines and primary
      MCL cells from the patients. We demonstrated that MYC is a bona fide client of
      HSP90 in the context of MCL by both immunoprecipitation and chemical
      precipitation. Furthermore, inhibition of HSP90 using PU-H71 induced apoptosis
      and caused cell cycle arrest. PU-H71 also demonstrates strong and relatively
      specific inhibition of the MYC transcriptional program compared with other
      oncogenic pathways. In a MCL patient-derived xenograft model, the HSP90 inhibitor
      retards tumor growth and prolongs survival. Last, we showed that PU-H71 induced
      apoptosis and downregulated MYC protein in MCL cells derived from patients who
      were clinically resistant to ibrutinib. In conclusion, MYC activity underlies
      intrinsic resistance to ibrutinib in MCL. As a client protein of HSP90, MYC can
      be inhibited via PU-H71 to overcome primary ibrutinib resistance.

PMID- 30115642
TI  - Computational modeling and confirmation of leukemia-associated minor
      histocompatibility antigens.
AB  - T-cell responses to minor histocompatibility antigens (mHAs) mediate both
      antitumor immunity (graft-versus-leukemia [GVL]) and graft-versus-host disease
      (GVHD) in allogeneic stem cell transplant. Identifying mHAs with high allele
      frequency, tight binding affinity to common HLA molecules, and narrow tissue
      restriction could enhance immunotherapy against leukemia. Genotyping and HLA
      allele data from 101 HLA-matched donor-recipient pairs (DRPs) were
      computationally analyzed to predict both class I and class II mHAs likely to
      induce either GVL or GVHD. Roughly twice as many mHAs were predicted in HLA
      matched unrelated donor (MUD) stem cell transplantation (SCT) compared with HLA
      matched related transplants, an expected result given greater genetic disparity
      in MUD SCT. Computational analysis predicted 14 of 18 previously identified mHAs,
      with 2 minor antigen mismatches not being contained in the patient cohort, 1
      missed mHA resulting from a noncanonical translation of the peptide antigen, and
      1 case of poor binding prediction. A predicted peptide epitope derived from GRK4,
      a protein expressed in acute myeloid leukemia and testis, was confirmed by
      targeted differential ion mobility spectrometry-tandem mass spectrometry. T cells
      specific to UNC-GRK4-V were identified by tetramer analysis both in DRPs where a
      minor antigen mismatch was predicted and in DRPs where the donor contained the
      allele encoding UNC-GRK4-V, suggesting that this antigen could be both an mHA and
      a cancer-testis antigen. Computational analysis of genomic and transcriptomic
      data can reliably predict leukemia-associated mHA and can be used to guide
      targeted mHA discovery.

PMID- 30115645
TI  - Brain Uptake of [13C] and [14C]Sucrose Quantified by Microdialysis and Whole
      Tissue Analysis in Mice.
AB  - Among small, hydrophilic drug-like molecules, [14C]sucrose has long been
      considered the gold standard for determination of blood-brain barrier
      permeability. However, we have recently shown in rats that, compared with liquid
      chromatography-tandem mass spectrometry analysis of stable isotope (13C) of
      sucrose, [14C]sucrose significantly overestimates the brain tissue concentration
      and uptake of sucrose by a factor of 6 to 7. This discrepancy is due to the
      presence of small quantities of lipophilic impurities in [14C]sucrose tracer
      solutions. Here, we used intracranial microdialysis to measure concentrations of
      both sucrose variants in brain extracellular fluid (ECF) after intravenous bolus
      administration to mice. Both markers displayed similar plasma profiles and ECF
      dialysate concentrations. However, total brain tissue concentrations and apparent
      brain uptake clearance of [14C]sucrose were 4.1- and 3.6-fold higher,
      respectively, than those of [13C]sucrose. Therefore, the contaminants of
      [14C]sucrose with higher permeability were likely sequestered by brain cells,
      which renders them nondialyzable. It is concluded that although measurement of
      radioactivity overestimates the concentrations of intact sucrose in the brain
      tissue, the ECF radioactivity after microdialysis is a relatively accurate
      reflection of intact sucrose after the systemic administration of the
      [14C]sucrose marker.

PMID- 30115644
TI  - Retinal Cholesterol Content Is Reduced in Simvastatin-Treated Mice Due to
      Inhibited Local Biosynthesis Albeit Increased Uptake of Serum Cholesterol.
AB  - Statins, a class of cholesterol-lowering drugs, are currently being investigated
      for treatment of age-related macular degeneration, a retinal disease. Herein,
      retinal and serum concentrations of four statins (atorvastatin, simvastatin,
      pravastatin, and rosuvastatin) were evaluated after mice were given a single drug
      dose of 60 mg/kg body weight. All statins, except rosuvastatin, were detected in
      the retina: atorvastatin and pravastatin at 1.6 pmol and simvastatin at 4.1 pmol.
      Serum statin concentrations (pmol/ml) were 223 (simvastatin), 1401
      (atorvastatin), 2792 (pravastatin), and 9050 (rosuvastatin). Simvastatin was then
      administered to mice daily for 6 weeks at 60 mg/kg body weight. Simvastatin
      treatment reduced serum cholesterol levels by 18% and retinal content of
      cholesterol and lathosterol (but not desmosterol) by 24% and 21%, respectively.
      The relative contributions of retinal cholesterol biosynthesis and retinal uptake
      of serum cholesterol to total retinal cholesterol input were changed as well.
      These contributions were 79% and 21%, respectively, in vehicle-treated mice and
      69% and 31%, respectively, in simvastatin-treated mice. Thus, simvastatin
      treatment lowered retinal cholesterol because a compensatory upregulation of
      retinal uptake of serum cholesterol was not sufficient to overcome the effect of
      inhibited retinal biosynthesis. Simultaneously, simvastatin-treated mice had a
      2.9-fold increase in retinal expression of Cd36, the major receptor clearing
      oxidized low-density lipoproteins from Bruch's membrane. Notably, simvastatin
      treatment essentially did not affect brain cholesterol homeostasis. Our results
      reveal the statin effect on the retinal and brain cholesterol input and are of
      value for future clinical investigations of statins as potential therapeutics for
      age-related macular degeneration.

PMID- 30115646
TI  - Mouse Hepatomas with Ha-ras and B-raf Mutations Differ in Mitogen-Activated
      Protein Kinase Signaling and Response to Constitutive Androstane Receptor
      Activation.
AB  - Nuclear receptors mediate the hepatic induction of drug-metabolizing enzymes by
      xenobiotics. Not much is known about enzyme induction in liver tumors. Here, we
      treated tumor-bearing mice with phenobarbital, an activator of the constitutive
      androstane receptor (CAR), to analyze the response of chemically induced Ha-ras-
      and B-raf-mutated mouse liver adenoma to CAR activation in vivo. Both tumor
      subpopulations possess almost identical gene expression profiles. CAR target gene
      induction in the tumors was studied at the mRNA and protein levels, and a reverse
      phase protein microarray approach was chosen to characterize important signaling
      cascades. CAR target gene induction was pronounced in B-raf-mutated but not in Ha
      ras-mutated tumors. Phosphoproteomic profiling revealed that phosphorylation
      activated extracellular signal-regulated kinase (ERK) 1/2 was more abundant in Ha
      ras-mutated than in B-raf-mutated tumors. ERK activation in tumor tissue was
      negatively correlated with CAR target induction. ERK activation is known to
      inhibit CAR-dependent transcription. In summary, profound differences exist
      between the two closely related tumor subpopulations with respect to the
      activation of mitogenic signaling cascades, and these dissimilarities might
      explain the differences in xenobiotic induction of CAR target genes.

PMID- 30115648
TI  - Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans
      for 1352 Drug Compounds.
AB  - We report a trend analysis of human intravenous pharmacokinetic data on a data
      set of 1352 drugs. The aim in building this data set and its detailed analysis
      was to provide, as in the previous case published in 2008, an extended, robust,
      and accurate resource that could be applied by drug metabolism, clinical
      pharmacology, and medicinal chemistry scientists to a variety of scaling
      approaches. All in vivo data were obtained or derived from original references,
      either through the literature or regulatory agency reports, exclusively from
      studies utilizing intravenous administration. Plasma protein binding data were
      collected from other available sources to supplement these pharmacokinetic data.
      These parameters were analyzed concurrently with a range of physicochemical
      properties, and resultant trends and patterns within the data are presented. In
      addition, the date of first disclosure of each molecule was reported and the
      potential "temporal" impact on data trends was analyzed. The findings reported
      here are consistent with earlier described trends between pharmacokinetic
      behavior and physicochemical properties. Furthermore, the availability of a large
      data set of pharmacokinetic data in humans will be important to further pursue
      analyses of physicochemical properties, trends, and modeling efforts and should
      propel our deeper understanding (especially in terms of clearance) of the
      absorption, distribution, metabolism, and excretion behavior of drug compounds.

PMID- 30115647
TI  - When Does the Rate-Determining Step in the Hepatic Clearance of a Drug Switch
      from Sinusoidal Uptake to All Hepatobiliary Clearances? Implications for
      Predicting Drug-Drug Interactions.
AB  - For dual transporter-enzyme substrate drugs, the extended clearance model can be
      used to predict the rate-determining step(s) (RDS) of a drug and hence predict
      its drug-drug interaction (DDI) liabilities (i.e., transport, metabolism, or
      both). If the RDS of the hepatic clearance of the drug is sinusoidal uptake
      clearance (CLs in), even if the drug is eliminated mainly by hepatic metabolism,
      its DDI liability (as viewed from changes to systemic drug concentrations) is
      expected to be inhibition or induction of uptake transporters but not hepatic
      enzymes; however, this is true only if the condition required to maintain CLs in
      as the RDS is maintained. Here, we illustrate through theoretical simulations
      that the RDS condition may be violated in the presence of a DDI. That is, the RDS
      of a drug can switch from CLs in to all hepatobiliary clearances [i.e.,
      metabolic/biliary clearance (CLmet + bile) and CLs in], leading to unexpected
      systemic DDIs, such as metabolic DDIs, when only transporter DDIs were
      anticipated. As expected, these analyses revealed that the RDS switch depends on
      the ratio of CLmet + bile to sinusoidal efflux clearance (CLs ef). Additional
      analyses revealed that for intravenously administered drugs, the RDS switch also
      depends on the magnitude of CLs in We analyzed published in vitro quantified
      hepatobiliary clearances and observed that most drugs have a CLmet + bile/CLs ef
      ratio < 4; hence, in practice, the magnitude of CLs in must be considered when
      establishing the RDS. These analyses provide insights previously not appreciated
      and a theoretical framework to predict DDI liabilities for drugs that are dual
      transporter-enzyme substrates.

PMID- 30115649
TI  - Somatostatin Is Only Partly Required for the Glucagonostatic Effect of Glucose
      but Is Necessary for the Glucagonostatic Effect of KATP Channel Blockers.
AB  - The mechanisms of control of glucagon secretion are largely debated. In
      particular, the paracrine role of somatostatin (SST) is unclear. We studied its
      role in the control of glucagon secretion by glucose and KATP channel blockers,
      using perifused islets and the in situ perfused pancreas. The involvement of SST
      was evaluated by comparing glucagon release of control tissue or tissue without
      paracrine influence of SST (pertussis toxin-treated islets, or islets or pancreas
      from Sst-/- mice). We show that removal of the paracrine influence of SST
      suppresses the ability of KATP channel blockers or KATP channel ablation to
      inhibit glucagon release, suggesting that in control islets, the glucagonostatic
      effect of KATP channel blockers/ablation is fully mediated by SST. By contrast,
      the glucagonostatic effect of glucose in control islets is mainly independent of
      SST for low glucose concentrations (0-7 mmol/L) but starts to involve SST for
      high concentrations of the sugar (15-30 mmol/L). This demonstrates that the
      glucagonostatic effect of glucose only partially depends on SST. Real-time
      quantitative PCR and pharmacological experiments indicate that the
      glucagonostatic effect of SST is mediated by two types of SST receptors, SSTR2
      and SSTR3. These results suggest that alterations of the paracrine influence of
      SST will affect glucagon release.

PMID- 30115651
TI  - A Systemic Inflammatory Signature Reflecting Cross Talk Between Innate and
      Adaptive Immunity Is Associated With Incident Polyneuropathy: KORA F4/FF4 Study.
AB  - Prospective analyses of biomarkers of inflammation and distal sensorimotor
      polyneuropathy (DSPN) are scarce and limited to innate immunity. We therefore
      aimed to assess associations between biomarkers reflecting multiple aspects of
      immune activation and DSPN. The study was based on 127 case subjects with
      incident DSPN and 386 noncase subjects from the population-based Cooperative
      Health Research in the Region of Augsburg (KORA) F4/FF4 cohort (follow-up 6.5
      years). Proximity extension assay technology was used to measure serum levels of
      biomarkers of inflammation. Of 71 biomarkers assessed, 26 were associated with
      incident DSPN. After adjustment for multiple testing, higher levels of six
      biomarkers remained related to incident DSPN. Three of these proteins (MCP
      3/CCL7, MIG/CXCL9, IP-10/CXCL10) were chemokines, and the other three (DNER,
      CD40, TNFRSF9) were soluble forms of transmembrane receptors. The chemokines had
      neurotoxic effects on neuroblastoma cells in vitro. Addition of all six
      biomarkers improved the C statistic of a clinical risk model from 0.748 to 0.783
      (P = 0.011). Pathway analyses indicated that multiple cell types from innate and
      adaptive immunity are involved in the development of DSPN. We thus identified
      novel associations between biomarkers of inflammation and incident DSPN pointing
      to a complex cross talk between innate and adaptive immunity in the pathogenesis
      of the disease.

PMID- 30115650
TI  - Podocyte-Specific Loss of Kruppel-Like Factor 6 Increases Mitochondrial Injury in
      Diabetic Kidney Disease.
AB  - Mitochondrial injury is uniformly observed in several murine models as well as in
      individuals with diabetic kidney disease (DKD). Although emerging evidence has
      highlighted the role of key transcriptional regulators in mitochondrial
      biogenesis, little is known about the regulation of mitochondrial cytochrome c
      oxidase assembly in the podocyte under diabetic conditions. We recently reported
      a critical role of the zinc finger Kruppel-like factor 6 (KLF6) in maintaining
      mitochondrial function and preventing apoptosis in a proteinuric murine model. In
      this study, we report that podocyte-specific knockdown of Klf6 increased the
      susceptibility to streptozotocin-induced DKD in the resistant C57BL/6 mouse
      strain. We observed that the loss of KLF6 in podocytes reduced the expression of
      synthesis of cytochrome c oxidase 2 with resultant increased mitochondrial
      injury, leading to activation of the intrinsic apoptotic pathway under diabetic
      conditions. Conversely, mitochondrial injury and apoptosis were significantly
      attenuated with overexpression of KLF6 in cultured human podocytes under
      hyperglycemic conditions. Finally, we observed a significant reduction in
      glomerular and podocyte-specific expression of KLF6 in human kidney biopsies with
      progression of DKD. Collectively, these data suggest that podocyte-specific KLF6
      is critical to preventing mitochondrial injury and apoptosis under diabetic
      conditions.

PMID- 30115652
TI  - Contribution of the Long Noncoding RNA H19 to beta-Cell Mass Expansion in
      Neonatal and Adult Rodents.
AB  - Pancreatic beta-cell expansion throughout the neonatal period is essential to
      generate the appropriate mass of insulin-secreting cells required to maintain
      blood glucose homeostasis later in life. Hence, defects in this process can
      predispose to diabetes development during adulthood. Global profiling of
      transcripts in pancreatic islets of newborn and adult rats revealed that the
      transcription factor E2F1 controls expression of the long noncoding RNA H19,
      which is profoundly downregulated during the postnatal period. H19 silencing
      decreased beta-cell expansion in newborns, whereas its re-expression promoted
      proliferation of beta-cells in adults via a mechanism involving the microRNA let
      7 and the activation of Akt. The offspring of rats fed a low-protein diet during
      gestation and lactation display a small beta-cell mass and an increased risk of
      developing diabetes during adulthood. We found that the islets of newborn rats
      born to dams fed a low-protein diet express lower levels of H19 than those born
      to dams that did not eat a low-protein diet. Moreover, we observed that H19
      expression increases in islets of obese mice under conditions of increased
      insulin demand. Our data suggest that the long noncoding RNA H19 plays an
      important role in postnatal beta-cell mass expansion in rats and contributes to
      the mechanisms compensating for insulin resistance in obesity.

PMID- 30115654
TI  - Radiological diagnosis of interstitial lung disease: is it all about pattern
      recognition?

PMID- 30115653
TI  - Whole-Organism Chemical Screening Identifies Modulators of Pancreatic beta-Cell
      Function.
AB  - beta-Cell loss and dysfunction play a critical role in the progression of type 1
      and type 2 diabetes. Identifying new molecules and/or molecular pathways that
      improve beta-cell function and/or increase beta-cell mass should significantly
      contribute to the development of new therapies for diabetes. Using the zebrafish
      model, we screened 4,640 small molecules to identify modulators of beta-cell
      function. This in vivo strategy identified 84 stimulators of insulin expression,
      which simultaneously reduced glucose levels. The insulin promoter activation
      kinetics for 32 of these stimulators were consistent with a direct mode of
      action. A subset of insulin stimulators, including the antidiabetic drug
      pioglitazone, induced the coordinated upregulation of gluconeogenic pck1
      expression, suggesting functional response to increased insulin action in
      peripheral tissues. Notably, Kv1.3 inhibitors increased beta-cell mass in larval
      zebrafish and stimulated beta-cell function in adult zebrafish and in the
      streptozotocin-induced hyperglycemic mouse model. In addition, our data indicate
      that cytoplasmic Kv1.3 regulates beta-cell function. Thus, using whole-organism
      screening, we have identified new small-molecule modulators of beta-cell function
      and glucose metabolism.

PMID- 30115655
TI  - Cold storage of platelets in additive solution: The impact of residual plasma in
      apheresis platelet concentrates.
AB  - Platelet transfusion became an indispensable therapy in the modern medicine.
      Although the clinical advantage of platelet transfusion is well established,
      adverse reactions upon transfusion, especially transmission of bacterial
      infection, still represent a major challenge. While bacterial contamination is
      favored by the storage of platelets at room temperature, cold storage may
      represent a solution for this clinically relevant issue. In this study, we aimed
      to elucidate whether plasma has protective or detrimental effects on cold-stored
      platelets. We investigated the impact of different residual plasma contents in
      apheresis-derived platelet concentrates, stored at 4 degrees ;C or room
      temperature, on platelet function and survival. We found that platelets stored at
      4 degrees C have higher expression of apoptosis marker compared to room
      temperature-stored platelets leading to an accelerated clearance from the
      circulation in a humanized animal model. While cold-induced apoptosis was
      independent of the residual plasma concentration, cold storage was associated
      with better adhesive properties and higher response to activators. Of note, delta
      granule-related functions, such as ADP-mediated aggregation and CD63 release,
      were better preserved at 4 degrees C especially in 100% plasma. An extended study
      to assess cold-stored platelet concentrates produced under standard care GMP
      conditions showed that platelet function, metabolism and integrity were better
      compared to those stored at room temperature. Taken together, our results show
      that residual plasma concentration does not have a cardinal impact on the cold
      storage lesions of apheresis-derived platelet concentrates and indicate that the
      current generation of additive solutions is suitable substitutes for plasma to
      store platelets at 4 degrees C.

PMID- 30115656
TI  - Feasibility and efficacy of addition of individualized dose lenalidomide to
      chlorambucil and rituximab as first-line treatment in elderly and FCR-unfit
      patients with advanced chronic lymphocytic leukemia.
AB  - BACKGROUND: Lenalidomide (Len) has been proven effective both as monotherapy and
      in combination with rituximab for the treatment of chronic lymphocytic leukemia
      (CLL). Len has shown a distinct and more difficult to manage toxicity profile in
      the context of CLL, potentially hampering combination treatment with this drug.
      METHODS: In 1st-line CLL elderly and fludarabine, cyclophosphamide, rituximab
      (FCR) unfit patients, we conducted a phase 1-2 study to evaluate efficacy and
      safety of 6 cycles of chlorambucil (7mg/m2 on days 1-7), rituximab (375mg/m2
      cycle 1 and 500mg/m2 cycle 2-6) and individual dosed Len (started on day 9 of
      cycle 1 2.5 mg, cycle 2 5 mg and cycle 3 and up 10 mg or maximum tolerated dose
      (MTD)) (induction-I). This was followed by 6 months of Len monotherapy at the MTD
      (induction-II). The primary endpoint was the overall response rate (ORR) after
      induction-I. RESULTS: Of 53 evaluable patients in phase 2, 47 patients (89%)
      completed induction-I and 36 patients (68%) completed induction-II. In an
      intention-to-treat analysis, the ORR was 83%. The median progression free
      survival (PFS) was 49 months, after a median follow-up time of 27 months. The 2-
      and 3-year PFS rate was 58% (standard error [SE]=8%) and 54% (SE=8%),
      respectively. The corresponding rate for OS was 98% (SE=2%) and 95% (SE=3%). No
      tumor lysis syndrome was observed, while tumor flair reaction occurred in 5
      patients (9%, 1 grade 3). Most common hematologic toxicity was grade 3-4
      neutropenia in 73%. CONCLUSIONS: Addition of Len to a backbone of chlorambucil
      and rituximab followed by a fixed duration of Len monotherapy in 1st line elderly
      and FCR-unfit patients results in high remission rates and PFS rates, that seem
      comparable to those observed with novel combinations including novel CD20
      monoclonal antibodies or kinase inhibitors. Although Len-specific toxicity
      remains a concern, an individualized dose-escalation schedule is feasible and
      results in an acceptable toxicity profile.

PMID- 30115657
TI  - Relationship between CD33 expression, splicing polymorphism, and in vitro
      cytotoxicity of gemtuzumab ozogamicin and the CD33/CD3 BiTErAMG 330.

PMID- 30115658
TI  - Computed tomography pulmonary angiography versus ventilation-perfusion lung scan
      for pulmonary embolism diagnosis during pregnancy: a systematic review and meta
      analysis.
AB  - Differences of computed tomography pulmonary angiography versus ventilation
      perfusion lung scan in pregnant patients with suspected acute pulmonary embolism
      are not well-known, leading to ongoing debate on which test to choose. We
      searched in PUBMED, EMBASE, Web of science and Cochrane library databases and
      identified all relevant articles and abstracts published up to October1st 2017.
      We assessed diagnostic efficiency, frequency of non-diagnostic results and
      radiation exposure for patient and fetus. We included 13 studies for the
      diagnostic efficiency analysis, 30 for non-diagnostic results analysis and 22 for
      radiation exposure analysis. Pooled rate of false negative test results was 0%
      for both imaging strategies with overlapping confidence intervals. The pooled
      rate of non-diagnostic results with computed tomography pulmonary angiography and
      ventilation-perfusion lung scan were 12% (95%CI 8-17) and 14% (95%CI 10-18),
      respectively. Reported maternal and fetal radiation exposure doses were well
      below the safety threshold, but could not be compared between computed tomography
      pulmonary angiography and ventilation-perfusion lung scan given the lack of high
      quality data. Both imaging tests seem equally safe to rule out PE in pregnancy.
      We found no significant differences in efficiency and radiation exposures between
      computed tomography pulmonary angiography and ventilation-perfusion lung scan
      although direct comparisons were not possible. .

PMID- 30115659
TI  - A mutation in the gene coding for the sialic acid transporter SLC35A1 is required
      for platelet life span but not proplatelet formation.

PMID- 30115660
TI  - Macrophage ferroportin is essential for stromal cell proliferation in wound
      healing.
AB  - Iron recycling by macrophages is essential for erythropoiesis, but may be also
      relevant for iron redistribution to neighbouring cells at the local tissue level.
      Using mice with iron retention in macrophages due to targeted inactivation of the
      iron exporter ferroportin, we investigated the role of macrophage iron release in
      hair follicle cycling and wound healing, a complex process leading to major
      clinical problems, if impaired. Genetic deletion of ferroportin in macrophages
      resulted in iron deficiency and decreased proliferation in epithelial cells,
      which consequently impaired hair follicle growth and caused transient alopecia.
      Hair loss was not related to systemic iron deficiency or anemia, thus indicating
      the necessity of local iron release from macrophages. Inactivation of macrophage
      ferroportin also led to delayed skin wound healing with defective granulation
      tissue formation and diminished fibroplasia. Iron retention in macrophages had no
      impact on the inflammatory processes accompanying wound healing, but affected
      stromal cells proliferation, blood and lymphatic vessels formation, and
      fibrogenesis. Our findings reveal that iron/ferroportin plays a largely
      underestimated role in the macrophage trophic function in skin homeostasis and
      repair.

PMID- 30115662
TI  - Propofol's paradox, explained.
AB  - Tandem JGP studies investigate how propofol affects voltage-gated sodium
      channels.

PMID- 30115661
TI  - Phenotypic plasticity in Periplaneta americana photoreceptors.
AB  - Plasticity is a crucial aspect of neuronal physiology essential for proper
      development and continuous functional optimization of neurons and neural
      circuits. Despite extensive studies of different visual systems, little is known
      about plasticity in mature microvillar photoreceptors. Here we investigate
      changes in electrophysiological properties and gene expression in photoreceptors
      of the adult cockroach, Periplaneta americana, after exposure to constant light
      (CL) or constant dark (CD) for several months. After CL, we observed a decrease
      in mean whole-cell capacitance, a proxy for cell membrane area, from 362 +/- 160
      to 157 +/- 58 pF, and a decrease in absolute sensitivity. However, after CD, we
      observed an increase in capacitance to 561 +/- 155 pF and an increase in absolute
      sensitivity. Small changes in the expression of light-sensitive channels and
      signaling molecules were detected in CD retinas, together with a substantial
      increase in the expression of the primary green-sensitive opsin (GO1).
      Accordingly, light-induced currents became larger in CD photoreceptors. Even
      though normal levels of GO1 expression were retained in CL photoreceptors, light
      induced currents became much smaller, suggesting that factors other than opsin
      are involved. Latency of phototransduction also decreased significantly in CL
      photoreceptors. Sustained voltage-activated K+ conductance was not significantly
      different between the experimental groups. The reduced capacitance of CL
      photoreceptors expanded their bandwidth, increasing the light-driven voltage
      signal at high frequencies. However, voltage noise was also amplified, probably
      because of unaltered expression of TRPL channels. Consequently, information
      transfer rates were lower in CL than in control or CD photoreceptors. These
      changes in whole-cell capacitance and electrophysiological parameters suggest
      that structural modifications can occur in the photoreceptors to adapt their
      function to altered environmental conditions. The opposing patterns of
      modifications in CL and CD photoreceptors differ profoundly from previous
      findings in Drosophila melanogaster photoreceptors.

PMID- 30115663
TI  - Progress in understanding slow inactivation speeds up.

PMID- 30115664
TI  - Preclinical Efficacy of the Novel Monocarboxylate Transporter 1 Inhibitor BAY
      8002 and Associated Markers of Resistance.
AB  - The lactate transporter SLC16A1/monocarboxylate transporter 1 (MCT1) plays a
      central role in tumor cell energy homeostasis. In a cell-based screen, we
      identified a novel class of MCT1 inhibitors, including BAY-8002, which potently
      suppress bidirectional lactate transport. We investigated the antiproliferative
      activity of BAY-8002 in a panel of 246 cancer cell lines and show that
      hematopoietic tumor cells, in particular diffuse large B-cell lymphoma cell
      lines, and subsets of solid tumor models are particularly sensitive to MCT1
      inhibition. Associated markers of sensitivity were, among others, lack of MCT4
      expression, low pleckstrin homology like domain family A member 2, and high
      pellino E3 ubiquitin protein ligase 1 expression. The antitumor effect of MCT1
      inhibition was less pronounced on tumor xenografts, with tumor stasis being the
      maximal response. BAY-8002 significantly increased intratumor lactate levels and
      transiently modulated pyruvate levels. In order to address potential acquired
      resistance mechanisms to MCT1 inhibition, we generated MCT1 inhibitor-resistant
      cell lines and show that resistance can occur by upregulation of MCT4 even in the
      presence of sufficient oxygen, as well as by shifting energy generation toward
      oxidative phosphorylation. These findings provide insight into novel aspects of
      tumor response to MCT1 modulation and offer further rationale for patient
      selection in the clinical development of MCT1 inhibitors. Mol Cancer Ther;
      17(11); 2285-96. (c)2018 AACR.

PMID- 30115665
TI  - Uranium isotope fractionation by abiotic reductive precipitation.
AB  - Significant uranium (U) isotope fractionation has been observed during abiotic
      reduction of aqueous U, counter to the expectation that uranium isotopes are only
      fractionated by bioassociated enzymatic reduction. In our experiments, aqueous U
      is removed from solution by reductive precipitation onto the surfaces of
      synthetic iron monosulfide. The magnitude of uranium isotopic fractionation
      increases with decreasing aqueous U removal rate and with increasing amounts of
      neutrally charged aqueous Ca-U-CO3 species. Our discovery means that abiotic U
      isotope fractionation likely occurs in any reducing environment with aqueous Ca
      >= 1 mM, and that the magnitude of isotopic fractionation changes in response to
      changes in aqueous major ion concentrations that affect U speciation. Our results
      have implications for the study of anoxia in the ancient oceans and other
      environments.

PMID- 30115666
TI  - Extreme bioengineering to meet the nitrogen challenge.

PMID- 30115668
TI  - Neuronal endosomes to lysosomes: A journey to the soma.
AB  - How are lysosomal degradation pathways spatially organized in the complex
      landscape of a neuron? Cheng et al. (2018. J Cell Biol.
      https://doi.org/10.1083/jcb.201711083) and Yap et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201711039) characterize the distribution and function
      of endolysosomal organelles in neurons, providing insights into compartment
      specific mechanisms regulating the neuronal proteome.

PMID- 30115667
TI  - Cell cycle pacemaker keeps adhesion in step with division.
AB  - Adherent cells round up before division but it is unclear how detachment is
      regulated by the cell cycle. In this issue, Jones et al. (2018. J. Cell Biol.
      https://doi.org/10.1083/jcb.201802088) find the kinase CDK1 maintains adhesion
      during interphase by phosphorylating integrin adhesome proteins, including the
      formin FMNL2, and loss of this function of CDK1 activity in G2 triggers adhesion
      disassembly.

PMID- 30115669
TI  - Prospective assessment of the diagnostic and prognostic utility of rotational
      thromboelastometry for canine disseminated intravascular coagulation.
AB  - This study compared the haematological, haemostatic and thromboelastometric (TEM)
      parameters between dogs with and without suspected disseminated intravascular
      coagulation (DIC). Seventy-six dogs with a medical condition known to predispose
      to DIC were prospectively included in the study. Thirty-eight dogs (50 per cent)
      presented with haemorrhagic diatheses. DIC was diagnosed in 32 dogs (42 per
      cent). Thirty-five dogs (46 per cent) had a normal TEM profile, 25 dogs (33 per
      cent) had a hypercoagulable profile and 16 dogs (21 per cent) had a
      hypocoagulable profile. Except for the lysis parameters, all TEM parameters were
      significantly correlated with the presence of DIC in univariate and multivariate
      analyses. Mortality rates were significantly higher in dogs with DIC (50 per
      cent) than in dogs without DIC (27 per cent, P=0.043; OR 2.667, 95 per cent CI
      1.049 to 6.701), and mortality rates were significantly higher in dogs with a
      hypocoagulable profile (69 per cent) than in dogs with a hypercoagulable (24 per
      cent, P=0.017; OR 4.800, 95 per cent CI 1.241 to 16.220) or a normal profile (31
      per cent, P=0.046; OR 3.429; 95 per cent CI 1.006 to 11.470). All TEM parameters
      were significantly associated with mortality in univariate and multivariate
      analyses. Thromboelastometry appears to be a valuable tool for the diagnosis and
      prognosis of dogs with suspected DIC, especially those with a hypocoagulable
      profile that was associated with increased risk of death and increased risk of
      haemorrhagic diatheses.

PMID- 30115670
TI  - Comparison of standard single-bite with multiple-bite biopsy forceps for
      collection of gastrointestinal biopsies in dogs: a prospective study.
AB  - Various types of endoscopic biopsy forceps have been investigated in dogs. The
      Multibite (MB) are multiple-bite forceps that collect up to four tissue specimens
      in a single pass through the endoscope, reducing procedure time. The authors
      prospectively investigated its clinical utility by comparing procedure times and
      diagnostic quality of samples obtained with the MB to that of biopsies performed
      with a single-bite forceps (SB), in 21 dogs with gastrointestinal disorders. When
      comparing the depth, crush artefacts and diagnostic adequacy of the gastric and
      duodenal biopsies, there was no significant difference between the MB and SB
      forceps. The procedure time was significantly longer with the MB. There was no
      learning curve effect, and there were no reported adverse events. This study
      failed to demonstrate any significant clinical advantage associated with the use
      of the Multibite forceps over that of conventional disposable SB forceps.

PMID- 30115671
TI  - How does the environment affect fighting? The interaction between extrinsic
      fighting ability and resource value during contests.
AB  - An individual's performance during a fight is influenced by a combination of
      their capacity and willingness to compete. While willingness to fight is known to
      be determined by both intrinsic and extrinsic drivers, an individual's capacity
      to fight is generally thought of as solely intrinsic, being driven by a host of
      physiological factors. However, evidence indicates that variation in fighting
      ability can also be generated through exposure to different environmental
      conditions. Environmental contributions to fighting ability may be particularly
      important for animals living in spatially and temporally heterogeneous habitats,
      in which fights can occur between rivals recently exposed to different
      environmental conditions. The rapidly changing environment experienced within
      intertidal zones, for example, means that seawater parameters, including
      dissolved oxygen content and temperature, can vary across small spatial and
      temporal scales. Here, we investigated the relative importance of these extrinsic
      contributions to fighting ability and resource value on contest dynamics in the
      beadlet sea anemone Actinia equina We manipulated the extrinsic fighting ability
      of both opponents (through dissolved oxygen concentration prior to fights) and
      resource value (through seawater flow rate during the fight). Our results
      indicate that the extrinsic fighting ability of both opponents can interact with
      resource value to drive escalation patterns and that extrinsic drivers can be
      more important in determining contest dynamics than the intrinsic traits commonly
      studied. Our study highlights the need to combine data on intrinsic state and
      extrinsic conditions in order to gain a more holistic view of the factors driving
      contest behaviour.

PMID- 30115672
TI  - Fluoxetine Affects Differentiation of Midbrain Dopaminergic Neurons In Vitro.
AB  - Recent meta-analyses found an association between prenatal exposure to the
      antidepressant fluoxetine (FLX) and an increased risk of autism in children. This
      developmental disorder has been related to dysfunctions in the brains' rewards
      circuitry, which, in turn, has been linked to dysfunctions in dopaminergic (DA)
      signaling. The present study investigated if FLX affects processes involved in
      dopaminergic neuronal differentiation. Mouse neuronal precursors were
      differentiated into midbrain dopaminergic precursor cells (mDPCs) and
      concomitantly exposed to clinically relevant doses of FLX. Subsequently,
      dopaminergic precursors were evaluated for expression of differentiation and
      stemness markers using quantitative polymerase chain reaction. FLX treatment led
      to increases in early regional specification markers orthodenticle homeobox 2
      (Otx2) and homeobox engrailed-1 and -2 (En1 and En2). On the other hand, two
      transcription factors essential for midbrain dopaminergic (mDA) neurogenesis, LIM
      homeobox transcription factor 1 alpha (Lmx1a) and paired-like homeodomain
      transcription factor 3 (Pitx3) were downregulated by FLX treatment. The stemness
      marker nestin (Nes) was increased, whereas the neuronal differentiation marker
      beta3-tubulin (Tubb3) decreased. Additionally, we observed that FLX modulates the
      expression of several genes associated with autism spectrum disorder and
      downregulates the estrogen receptors (ERs) alpha and beta Further investigations
      using ERbeta knockout (BERKO) mDPCs showed that FLX had no or even opposite
      effects on several of the genes analyzed. These findings suggest that FLX affects
      differentiation of the dopaminergic system by increasing production of
      dopaminergic precursors, yet decreasing their maturation, partly via interference
      with the estrogen system.

PMID- 30115673
TI  - Bortezomib Targets Sp Transcription Factors in Cancer Cells.
AB  - Bortezomib alone and in combination with other anticancer agents are extensively
      used for chemotherapeutic treatment of multiple myeloma (MM) patients and are
      being developed for treating other cancers. Bortezomib acts through multiple
      pathways, and in this study with ANBL-6 and RPMI 8226 MM cells we show that
      bortezomib inhibited growth and induced apoptosis and that this was accompanied
      by downregulation of specificity protein (Sp) 1, Sp3, and Sp4 transcription
      factors that are overexpressed in these cells. Similar results were observed in
      pancreatic and colon cancer cells. The functional importance of this pathway was
      confirmed by showing that individual knockdown of Sp1, Sp3, and Sp4 in MM cells
      inhibited cell growth and induced apoptosis, and that this correlates with the
      results of previous studies in pancreatic, colon, and other cancer cell lines.
      The mechanism of bortezomib-mediated downregulation of Sp transcription factors
      in MM was due to the induction of caspase-8 and upstream factors, including Fas
      associated death domain. These results demonstrate that an important underlying
      mechanism of action of bortezomib was due to the activation of caspase-8
      dependent downregulation of Sp1, Sp3, Sp4, and pro-oncogenic Sp-regulated genes.

PMID- 30115674
TI  - Toward a Better Understanding of Dural Arteriovenous Fistula Angioarchitecture:
      Superselective Transvenous Embolization of a Sigmoid Common Arterial Collector.
AB  - BACKGROUND AND PURPOSE: Our aim was to propose a conceptually new
      angioarchitectural model of some dural arteriovenous fistulas based on subset
      analysis of transverse and sigmoid type lesions. The "common collector" notion
      argues for convergence of multiple smaller caliber arterial vessels on a common
      arterial collector vessel within the sinus wall. Communication of this single
      collector (or constellation of terminal collectors) with the sinus proper defines
      the site of arteriovenous fistula, which can be closed by highly targeted
      embolization, preserving the sinus and avoiding unnecessary permeation of
      indirect arterial feeders. MATERIALS AND METHODS: One hundred consecutive dural
      arteriovenous shunts were examined. Thirty-six transverse/sigmoid fistulas were
      identified within this group and analyzed for the presence of a common arterial
      collector as well as other parameters, including demographics, grade, treatment
      approach, and outcome. RESULTS: A common collector was identified in nearly all
      Cognard type I lesions (15 fistulas with 14 single collector vessels seen) and
      progressively less frequently in higher grade fistulas. Identification of the
      common collector requires careful angiographic analysis, including supraselective
      and intraprocedural angiographies during treatment, and final embolic material
      morphology. CONCLUSIONS: Detailed evaluation of imaging studies allows frequent
      identification of a vascular channel in the sinus wall, which we argue reflects a
      compound, common arterial channel (rather than a venous collector) with 1 or
      several discrete fistulous points between this vessel and the sinus proper.
      Targeted closure of this channel is often feasible, with sinus preservation and
      avoidance of embolic material penetration into arteries remote from fistula site.

PMID- 30115675
TI  - Feasibility, Safety, and Periprocedural Complications Associated with
      Endovascular Treatment of Ruptured Intracranial Aneurysms according to the Depth
      of Anesthesia.
AB  - BACKGROUND AND PURPOSE: The aim of the present study was to report the
      feasibility, safety, and periprocedural complications associated with EVT of
      ruptured intracranial aneurysms according to the depth of anesthesia. In most
      centers, endovascular treatment of intracranial aneurysm is performed under
      general anesthesia. MATERIALS AND METHODS: Between March 2011 and December 2016,
      a total of 183 consecutive patients with 183 aneurysms were treated
      endovascularly at the authors' center. The data about the depth of anesthesia
      (local anesthesia, conscious sedation, deep sedation, and general anesthesia),
      procedural details, and clinical and radiologic outcomes were reviewed. RESULTS:
      A total of 183 consecutive patients with 183 aneurysms (mean age, 60.2 +/- 14.8
      years; 54 men and 129 women) were successfully treated. Of these, 70 (38.3%)
      patients underwent endovascular treatment under local anesthesia, 33 (18.0%)
      patients underwent endovascular treatment under conscious sedation, 78 (42.6%)
      patients underwent endovascular treatment under deep sedation, and only 2 (1.1%)
      patients underwent endovascular treatment under general anesthesia. For patients
      who presented with Hunt and Hess grades 1, 2, 3, 4, and 5, 75%, 59.6%, 59.1%,
      53.3%, and 35.3% were treated under local anesthesia or conscious sedation,
      respectively. The procedure-related complication rates amounted to 8.7% (16/183,
      with 11 thromboembolic complications and 5 intraprocedural ruptures) overall, and
      7.7% (14/183) of complications were symptomatic events. In the patients with good
      clinical grade (Hunt and Hess 1 or 2), the procedure-related complication rate
      was 4.1% (4/97), and all complications were symptomatic events under local
      anesthesia or conscious sedation. CONCLUSIONS: In the authors' experience, local
      anesthesia or conscious sedation seemed safe and feasible for the patients with
      good clinical grade SAH.

PMID- 30115676
TI  - MRI Findings in Tumefactive Demyelinating Lesions: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Accurate diagnosis of tumefactive demyelinating lesions is clinically
      important to avoid unnecessary invasive biopsy or inappropriate treatment.
      PURPOSE: We aimed to evaluate conventional and advanced MR imaging findings of
      tumefactive demyelinating lesions and determine the diagnostic performance of MR
      imaging for differentiating tumefactive demyelinating lesions from primary brain
      tumor. DATA SOURCES: A systematic search of Ovid MEDLINE and EMBASE up to
      December 6, 2017, was conducted. STUDY SELECTION: Original articles describing MR
      imaging findings in patients with tumefactive demyelinating lesions were
      selected. DATA ANALYSIS: The pooled incidences of conventional MR imaging
      findings of tumefactive demyelinating lesions were obtained with the DerSimonian
      and Liard random-effects model. The pooled sensitivity and specificity of MR
      imaging for differentiating tumefactive demyelinating lesions from primary brain
      tumor were obtained using the bivariate random-effects model. DATA SYNTHESIS:
      Nineteen eligible studies with 476 patients with tumefactive demyelinating
      lesions were included. The pooled incidence of open ring or incomplete rim
      enhancement was 35% (95% CI, 24%-47%), which was significantly higher than the
      incidence of closed ring or complete rim enhancement (18% [95% CI, 11%-29%]; P =
      .0281). The pooled incidences of T2 hypointense rim, absent or mild mass effect,
      and absent or mild perilesional edema were 48%, 67%, and 57%, respectively. On
      advanced MR imaging, tumefactive demyelinating lesions showed a high apparent
      diffusion coefficient, peripheral restricted diffusion, and low cerebral blood
      volume. The pooled sensitivity and specificity of MR imaging for differentiating
      tumefactive demyelinating lesions from primary brain tumor were 89% (95% CI, 82%
      93%) and 94% (95% CI, 89%-97%), respectively. LIMITATIONS: Seventeen of 19
      studies were retrospective studies. CONCLUSIONS: Conventional MR imaging findings
      may help differentiate tumefactive demyelinating lesions from primary brain
      tumor, though further study is needed to determine the added value of advanced MR
      imaging.

PMID- 30115677
TI  - Adult-Onset Leukoencephalopathy with Axonal Spheroids and Pigmented Glia: An MRI
      Study of 16 French Cases.
AB  - Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia is an
      autosomal dominant leukoencephalopathy related to CSF1R gene mutations. A growing
      number of clinicoradiologic phenotypes have been described. In this study, we
      analyzed brain imaging findings in 16 patients with adult-onset
      leukoencephalopathy with axonal spheroids and pigmented glia to refine radiologic
      diagnostic clues. T2/FLAIR white matter hyperintensities were present in all
      patients with frontal or frontoparietal predilection, with asymmetric
      distribution in more than one-third. Brain atrophy and callosal involvement were
      almost constant, and corticospinal tract involvement was frequent. Moreover, deep
      white matter hyperintense dots on DWI and deep punctate calcifications on CT were
      often found. Conversely, deep gray matter nuclei, external capsules, and brain
      stem were rarely involved. Our series emphasized the great variability of MR
      imaging findings seen in adult-onset leukoencephalopathy with axonal spheroids
      and pigmented glia. A complete imaging screening including DWI, T2*, and CT is
      mandatory to accurately assess patients with suspected inherited adult-onset
      leukoencephalopathy.

PMID- 30115678
TI  - Value of Contrast-Enhanced MRA versus Time-of-Flight MRA in Acute Ischemic Stroke
      MRI.
AB  - BACKGROUND AND PURPOSE: Vessel imaging in acute ischemic stroke is essential to
      select patients with large-vessel occlusion for mechanical thrombectomy. Our aim
      was to compare the diagnostic accuracy of time-of-flight MR angiography and
      contrast-enhanced MR angiography for identification of vessel occlusion and
      collateral status in acute ischemic stroke. MATERIALS AND METHODS: One hundred
      twenty-three patients with stroke with large-vessel occlusion before thrombectomy
      were included in this retrospective study. Before thrombectomy, 3T MR imaging,
      including conventional 3D TOF-MRA of the intracranial arteries and contrast
      enhanced MRA of intra- and extracranial arteries, was performed. Both techniques
      were assessed independently by 2 neuroradiologists for location of the occlusion,
      imaging quality, and collateral status. Findings were compared, with subsequent
      DSA as the reference standard. RESULTS: Both techniques had good interrater
      agreement of kappa = 0.74 (95% CI, 0.66-0.83) for TOF-MRA and kappa = 0.72 (95%
      CI, 0.63-0.80) for contrast-enhanced MRA. Occlusion localization differed
      significantly on TOF-MRA compared with DSA (P < .001), while no significant
      difference was observed between DSA and contrast-enhanced MRA (P = .75).
      Assessment of collaterals showed very good agreement between contrast-enhanced
      MRA and DSA (94.9% with P = .25), but only fair agreement between TOF-MRA and DSA
      (23.2% with P < .001). CONCLUSIONS: Contrast-enhanced MRA offers better
      diagnostic accuracy than TOF-MRA in acute ischemic stroke. Contrast-enhanced MRA
      was superior in localizing vessel occlusion within a shorter acquisition time
      while providing a larger coverage, including extracranial vessels, and a more
      accurate assessment of collateral status. These results support inclusion of
      contrast-enhanced MRA in acute stroke MR imaging, perhaps making TOF-MRA
      superfluous.

PMID- 30115679
TI  - Colorectal Cancer Incidence Trends by Age, Stage, and Racial/Ethnic Group in
      California, 1990-2014.
AB  - Background: The incidence of colorectal cancer in the United States declined
      substantially over the past 20 years, but evidence suggests that among younger
      adults (under 50 years at diagnosis), incidence is increasing. However, data on
      age- and stage-specific incidence trends across racial/ethnic groups are
      limited.Methods: All incident cases of colorectal cancer diagnosed from 1990
      through 2014 in adults aged 20 years and older were obtained from the California
      Cancer Registry. Incidence rates (per 100,000), incidence rate ratios, and
      triannual percent changes in incidence were estimated for each age group at
      diagnosis (20-49, 50-74, 75+ years), sex, stage, and race/ethnicity (non-Hispanic
      white, non-Hispanic black, Hispanic, and 7 Asian American groups).Results: Of
      349,176 incident colorectal cancer cases diagnosed from 1990 through 2014, 9%
      were in adults younger than 50 years. Increases in incidence of early-onset
      colorectal cancer, especially in regional/distant stage disease, were observed in
      most racial/ethnic groups (statistically significant for non-Hispanic whites and
      Hispanics, ranging from 0.9% to 2.9% every 3 years). Incidence also increased in
      Vietnamese and other Southeast Asian groups of screening age (50-74 years). The
      incidence of colorectal cancer in non-Hispanic blacks aged 50+ declined over the
      25-year period, but remained significantly higher than in non-Hispanic
      whites.Conclusions: Further research is needed to understand the causes of the
      increasing incidence of early-onset colorectal cancer. The rising incidence of
      colorectal cancer among Southeast Asians of screening age and the persistently
      high incidence in non-Hispanic blacks also warrant attention.Impact: Our findings
      may have implications for revisiting screening guidelines in the United States.
      Cancer Epidemiol Biomarkers Prev; 27(9); 1011-8. (c)2018 AACR.

PMID- 30115680
TI  - Linking Pediatrics Patients and Nurses With the Pharmacy and Electronic Health
      Record System Through the Inpatient Television: A Novel Interactive Pain
      Management Tool.
AB  - OBJECTIVES: Implement a novel pain-management interface that is used to bring
      real-time, patient-reported pain assessments to the inpatient television and
      evaluate the impact of implementation on the pain-management clinical workflow,
      patient engagement, and nursing pain reassessments. METHODS: We developed a pain
      management tool interfacing 4 stand-alone technologies: a television-based,
      interactive patient care system; electronic health record system; nursing call
      system; and pharmacy inventory-management system. The workflow is triggered when
      pain medications are dispensed by sending an automatic pain assessment rating
      question via the patient's television at a predefined time. To measure the
      effects of implementation, we calculated patient and/or parent use rates and pain
      reassessment timely documentation rates. Data were extracted from the electronic
      health record for a period of 22 months and covered pre- and postimplementation.
      RESULTS: A total of 56 931 patient records were identified during the study
      period, representing 2447 unique patients. In total, 608 parents and/or patients
      reported their pain through the tool. Use rates were 6.5% for responding to the
      pain rating prompt and 13.3% for the follow-up prompt, in which additional
      nonpharmacologic strategies to eliminate pain were offered. A modest increase was
      found in the mean timely documentation rates on the basis of nursing
      documentation standards (26.1% vs 32.8%, a percentage increase of 25.7%; P <
      .001) along with decreased median time to pain reassessment documentation (29
      minutes versus 25 minutes, a percentage decrease of 13.8%; P < .001).
      CONCLUSIONS: With this novel tool, we offer a potentially scalable approach in
      supporting the pain-management clinical workflow, integration of technologies,
      and promoting of patient and/or parent engagement in the inpatient setting.

PMID- 30115681
TI  - Mechanism of dysfunction of human variants of the IRAK4 kinase and a role for its
      kinase activity in interleukin-1 receptor signaling.
AB  - Interleukin-1 receptor (IL1R)-associated kinase 4 (IRAK4) is a central regulator
      of innate immune signaling, controlling IL1R and Toll-like receptor (TLR)
      mediated responses and containing both scaffolding and kinase activities. Humans
      deficient in IRAK4 activity have autosomal recessive primary immune deficiency
      (PID). Here, we characterized the molecular mechanism of dysfunction of two IRAK4
      PID variants, G298D and the compound variant R12C (R12C/R391H/T458I). Using these
      variants and the kinase-inactive D329A variant to delineate the contributions of
      IRAK4's scaffolding and kinase activities to IL1R signaling, we found that the
      G298D variant is kinase-inactive and expressed at extremely low levels, acting
      functionally as a null mutation. The R12C compound variant possessed WT kinase
      activity, but could not interact with myeloid differentiation primary response 88
      (MyD88) and IRAK1, causing impairment of IL-1-induced signaling and cytokine
      production. Quantitation of IL-1 signaling in IRAK4-deficient cells complemented
      with either WT or the R12C or D329A variant indicated that the loss of MyD88
      interaction had a greater impact on IL-1-induced signaling and cytokine
      expression than the loss of IRAK4 kinase activity. Importantly, kinase-inactive
      IRAK4 exhibited a greater association with MyD88 and a weaker association with
      IRAK1 in IRAK4-deficient cells expressing kinase-inactive IRAK4 and in primary
      cells treated with a selective IRAK4 inhibitor. Loss of IRAK4 kinase activity
      only partially inhibited IL-1-induced cytokine and NF-kappaB signaling.
      Therefore, the IRAK4-MyD88 scaffolding function is essential for IL-1 signaling,
      but IRAK4 kinase activity can control IL-1 signal strength by modulating the
      association of IRAK4, MyD88, and IRAK1.

PMID- 30115682
TI  - Identification of H4K20me3- and H3K4me3-associated RNAs using CARIP-Seq expands
      the transcriptional and epigenetic networks of embryonic stem cells.
AB  - RNA has been shown to interact with various proteins to regulate chromatin
      dynamics and gene expression. However, it is unknown whether RNAs associate with
      epigenetic marks such as post-translational modifications of histones, including
      histone 4 lysine 20 trimethylation (H4K20me3) or trimethylated histone 3 lysine 4
      (H3K4me3), to regulate chromatin and gene expression. Here, we used chromatin
      associated RNA immunoprecipitation (CARIP) followed by next-generation sequencing
      (CARIP-Seq) to survey RNAs associated with H4K20me3- and H3K4me3-marked chromatin
      on a global scale in embryonic stem (ES) cells. We identified thousands of mRNAs
      and noncoding RNAs that associate with H4K20me3- and H3K4me3-marked chromatin.
      H4K20me3- and H3K4me3-interacting RNAs are involved in chromatin organization and
      modification and RNA processing, whereas H4K20me3-only RNAs are involved in cell
      motility and differentiation, and H3K4me3-only RNAs are involved in metabolic
      processes and RNA processing. Expression of H3K4me3-associated RNAs is enriched
      in ES cells, whereas expression of H4K20me3-associated RNAs is enriched in ES
      cells and differentiated cells. H4K20me3- and H3K4me3-interacting RNAs originate
      from genes that co-localize with features of active chromatin, including
      transcriptional machinery and active promoter regions, and the histone
      modification H3K36me3 in gene body regions. We also found that H4K20me3 and
      H3K4me3 are associated with distinct gene features including transcripts of
      greater length and exon number relative to unoccupied transcripts. H4K20me3- and
      H3K4me3-marked chromatin is also associated with processed RNAs (exon
      transcripts) relative to unspliced pre-mRNA and ncRNA transcripts. In summary,
      our results provide evidence that H4K20me3- and H3K4me3-associated RNAs represent
      a distinct subnetwork of the ES cell transcriptional repertoire.

PMID- 30115683
TI  - Ciliary neurotrophic factor (CNTF) protects retinal cone and rod photoreceptors
      by suppressing excessive formation of the visual pigments.
AB  - The retinal pigment epithelium (RPE)-dependent visual cycle provides 11-cis
      retinal to opsins in the photoreceptor outer segments to generate functional
      visual pigments that initiate phototransduction in response to light stimuli.
      Both RPE65 isomerase of the visual cycle and the rhodopsin visual pigment have
      recently been identified as critical players in mediating light-induced retinal
      degeneration. These findings suggest that the expression and function of RPE65
      and rhodopsin need to be coordinately controlled to sustain normal vision and to
      protect the retina from photodamage. However, the mechanism controlling the
      development of the retinal visual system remains poorly understood. Here, we show
      that deficiency in ciliary neurotrophic factor (CNTF) up-regulates the levels of
      rod and cone opsins accompanied by an increase in the thickness of the outer
      nuclear layers and the lengths of cone and rod outer segments in the mouse
      retina. Moreover, retinoid isomerase activity, expression levels of RPE65 and
      lecithin:retinol acyltransferase (LRAT), which synthesizes the RPE65 substrate,
      were also significantly increased in the Cntf -/- RPE. Rod a-wave and cone b-wave
      amplitudes of electroretinograms were increased in Cntf -/- mice, but rod b-wave
      amplitudes were unchanged compared with those in WT mice. Up-regulated RPE65 and
      LRAT levels accelerated both the visual cycle rate and recovery rate of rod light
      sensitivity in Cntf -/- mice. Of note, rods and cones in Cntf -/- mice exhibited
      hypersusceptibility to light-induced degeneration. These results indicate that
      CNTF is a common extracellular factor that prevents excessive production of
      opsins, the photoreceptor outer segments, and 11-cis-retinal to protect rods and
      cones from photodamage.

PMID- 30115685
TI  - A substrate-trapping strategy for protein phosphatase PP1 holoenzymes using
      hypoactive subunit fusions.
AB  - The protein Ser/Thr phosphatase PP1 catalyzes an important fraction of protein
      dephosphorylation events and forms highly specific holoenzymes through an
      association with regulatory interactors of protein phosphatase one (RIPPOs). The
      functional characterization of individual PP1 holoenzymes is hampered by the lack
      of straightforward strategies for substrate mapping. Because efficient substrate
      recruitment often involves binding to both PP1 and its associated RIPPO, here we
      examined whether PP1-RIPPO fusions can be used to trap substrates for further
      analysis. Fusions of an hypoactive point mutant of PP1 and either of four tested
      RIPPOs accumulated in HEK293T cells with their associated substrates and were co
      immunoprecipitated for subsequent identification of the substrates by
      immunoblotting or MS analysis. Hypoactive fusions were also used to study RIPPOs
      themselves as substrates for associated PP1. In contrast, substrate trapping was
      barely detected with active PP1-RIPPO fusions or with nonfused PP1 or RIPPO
      subunits. Our results suggest that hypoactive fusions of PP1 subunits represent
      an easy-to-use tool for substrate identification of individual holoenzymes.

PMID- 30115684
TI  - Metabolic labeling of HIV-1 envelope glycoprotein gp120 to elucidate the effect
      of gp120 glycosylation on antigen uptake.
AB  - The glycan shield on the envelope glycoprotein gp120 of HIV-1 has drawn immense
      attention as a vulnerable site for broadly neutralizing antibodies and for its
      significant impact on host adaptive immune response to HIV-1. Glycosylation sites
      and glycan composition/structure at each site on gp120 along with the
      interactions of gp120 glycan shield with broadly neutralizing antibodies have
      been extensively studied. However, a method for directly and selectively tracking
      gp120 glycans has been lacking. Here, we integrate metabolic labeling and click
      chemistry technology with recombinant gp120 expression to demonstrate that gp120
      glycans could be specifically labeled and directly detected. Selective labeling
      of gp120 by N-azidoacetylmannosamine (ManNAz) and N-azidoacetylgalactosamine
      (GalNAz) incorporation into the gp120 glycan shield was characterized by MS of
      tryptic glycopeptides. By using metabolically labeled gp120, we investigated the
      impact of gp120 glycosylation on its interaction with host cells and demonstrated
      that oligomannose enrichment and sialic acid deficiency drastically enhanced
      gp120 uptake by bone marrow-derived dendritic cells. Collectively, our data
      reveal an effective labeling and detection method for gp120, serving as a tool
      for functional characterization of the gp120 glycans and potentially other
      glycosylated proteins.

PMID- 30115686
TI  - Peptide Receptor Radionuclide Therapy in Grade 3 Neuroendocrine Neoplasms: Safety
      and Survival Analysis in 69 Patients.
AB  - To date, limited data are available concerning peptide receptor radionuclide
      therapy (PRRT) of grade 3 (G3) neuroendocrine neoplasms (NENs) with a Ki-67
      proliferation index of >20%. The purpose of this study was to analyze the long
      term outcome, efficacy and safety of PRRT in patients with SSTR-expressing G3
      NEN. Methods: A total of 69 patients (M=41 males; age 28-81 years) received PRRT
      with lutetium-177 (177Lu) and/or yttium-90 (90Y) labeled somatostatin analogs
      (DOTATATE or DOTATOC). Twenty-two patients had radiosensitising chemotherapy.
      Kaplan-Meier analysis was performed to calculate progression-free survival (PFS)
      and overall survival (OS), defined from start of PRRT, including a subgroup
      analysis for patients with a Ki-67 of <=55% and >55%. Treatment response was
      evaluated according to RECIST 1.1 as well as by molecular imaging criteria
      (EORTC). Short and long-term toxicity was documented (CTCAE v.5.0) using a
      structured database (comprising over 250 items per patient) and retrospectively
      analyzed. Results: Forty-six patients had pancreatic, 11 CUP, 6 midgut, 3
      gastric, and 3 rectal NEN. Median follow-up was 94.3 months. The median PFS was
      9.6 months and median OS was 19.9 months. For G3 NEN with a Ki-67 <=55% (n = 53),
      the median PFS was 11 months and median OS 22 months. Patients with a Ki-67 >55%
      (n = 11), had a median PFS of 4 months and a median OS of 7 months. For those
      patients with positive SSTR imaging, but no FDG uptake, the median PFS was 24
      months and median OS was 42 months. A significant difference was found for both,
      PFS and OS, with a median PFS of 16 vs 5 months and a median OS of 27 vs 9 months
      for a SUVmax >15.0 and a SUVmax <=15.0 on SSTR-PET, respectively. In the group
      with FDG scored as 3-4, the median PFS was 7.1 months and the median OS 17.2
      months. For FDG scored as 0-2, the median PFS was 24.3 months and the median OS
      41.6 months. PRRT was well-tolerated by all patients; no grade 3 or grade 4
      hematotoxicity occurred and no clinically significant decline in renal function
      was observed. There was no hepatotoxicity. Conclusion: PRRT was tolerated well
      without significant adverse effects and is efficacious in G3 NEN with promising
      clinical outcome, especially in patients with a Ki-67 index of <=55% and even in
      patients who have failed chemotherapy. Baseline FDG along with SSTR molecular
      imaging is useful to stratify those G3-NEN patients with high uptake on SSTR
      PET/CT and no or minor FDG-avidity, a mismatch pattern which is associated with a
      better long term prognosis.

PMID- 30115687
TI  - THE WAR IS OPENED: PSMA VS. 64CuCL2 VS. CHOLINE PET/CT.

PMID- 30115688
TI  - Regional Artery Specific Thresholds Of Quantitative Myocardial Perfusion By PET
      Associated With Reduced MI and Death After Revascularization In Stable CAD.
AB  - Rationale: Since randomized coronary revascularization trials in stable CAD have
      shown no reduced MI or mortality, the threshold of quantitative myocardial
      perfusion severity was analyzed for association with reduced death, MI or stroke
      after revascularization within 90 days after PET. Methods: In a prospective long
      term cohort of stable CAD, regional, artery specific, quantitative myocardial
      perfusion by positron emission tomography (PET), coronary revascularization
      within 90 days after PET and all cause death, myocardial infarction and stroke
      (DMS) at 9 years follow-up, mean 3.0 +/- 2.3 years, were analyzed by multivariate
      Cox regression models and propensity analysis. Results: For 3774 sequential rest
      stress PET scans, regional, artery specific, severely reduced Coronary Flow
      Capacity (CFC) (CFR <= 1.27 and stress perfusion <= 0.83 cc/min/g) associated
      with 60% increased hazard ratio for major adverse cardiovascular events (MACE)
      and 30% increased hazard of DMS that was significantly reduced by 54% associated
      with revascularization within 90 days after PET (P = 0.0369), compared to
      moderate or mild CFC, CFR, other PET metrics or medical treatment alone.
      Depending on severity threshold for statistical certainty, up to 19% of this
      clinical cohort had CFC severity associated with reduced DMS after
      revascularization. Conclusion: Coronary Flow Capacity by PET provides objective,
      regional, artery specific, size-severity physiologic quantification of CAD
      severity associated with high risk of death, MI and stroke that is significantly
      reduced after revascularization within 90 days after PET, an association not seen
      for moderate to mild perfusion abnormalities or medical treatment alone.

PMID- 30115690
TI  - Twelve-year Follow-up after Peptide Receptor Radionuclide Therapy (PRRT).
AB  - Peptide receptor radionuclide therapy (PRRT) has been used for more than twenty
      years as a systemic treatment approach in inoperable or metastatic somatostatin
      receptor (SSTR)-positive tumors. The purpose of this study was to analyze the
      long-term outcome of PRRT with regard to the most commonly used
      radiopharmaceuticals, 90Y-DOTA-Tyr3-octreotide (90Y-DOTA-TOC) and 177Lu-DOTA-Tyr3
      octreotate (177Lu-DOTA-TATE). Methods: This retrospective clinical study included
      a total of 44 consecutive patients (27 men) with advanced tumors and enhanced
      SSTR expression. Mean age at initial diagnosis was 60 years (SD 11.3, range 40 to
      84 years). Median follow-up was 80 months. In the mean 5.3 +/- 2.5 cycles were
      administered for 177Lu-PRRT with mean activity of 27.2 +/- 14.9 GBq per patient
      and 5.5 +/- 2.6 cycles for 90Y-PRRT with mean activity of 14.7 +/- 7.3 GBq.
      Overall, 378 cycles were administered (mean 8.6 +/- 3.4 cycles per patient) with
      an overall cumulative activity of 1514.1 GBq. Results: Median overall survival
      (OS) was 79 months. Twenty-one (77.8%) of the 27 men and nine (52.9%) of the 17
      women had died 12 years after commencement of PRRT. Shortest duration of illness
      was eight months, longest 155 months. Severe side-effects (WHO Grades III and IV)
      are seen in nine of the 14 patients still alive. Chronic kidney disease in
      combination with anemia is the most common finding in the nine patients with
      severe side-effects. Very poor prognosis was found for those patients who showed
      progressive disease (PD) in comparison with patients with cumulative disease
      control after initial PRRT (log-rank, p<0.001), while women and patients with no
      more than two tumor sites seem to especially benefit from PRRT not reaching
      significance levels. Conclusion: PRRT is very encouraging in terms of long-term
      outcome. Thirty-two percent (14/44 patients) of the patients with metastatic or
      inoperable disease are still alive more than 12 years after the beginning of
      radionuclide therapy. Possible predictors for favourable outcome are initial
      response to PRRT, number of affected sites and female gender.

PMID- 30115689
TI  - Evaluation of a novel elastic respiratory motion correction algorithm on
      quantification and image quality in abdomino-thoracic PET/CT.
AB  - Our aim is to evaluate in phantom and patient studies a recently developed
      elastic motion debluring (EMDB) technique which makes use of all the acquired PET
      data and compare its performance to other conventional techniques such as phase
      based gating (PBG) and HDChest (HDC) both of which use fractions of the acquired
      data. Comparisons were made with respect to static whole-body (SWB) images with
      no motion correction. Methods: A phantom simulating respiratory motion of the
      thorax with lung lesions (5 spheres with ID=10- 28 mm) was scanned with 0, 1, 2,
      and 3 cm motion. Four reconstructions were performed: SWB, PBG, HDC, and EMDB.
      For PBG, the average (PBGave) and maximum bin (PBGmax) were used. To compare the
      reconstructions, the ratios of SUVmax (RSmax), SUVpeak (RSpeak), and CNR (RCNR)
      were calculated with respect to SWB. Additionally, 46 patients with lung or liver
      tumors < 3 cm diameter were also studied. Measurements of SUVmax, SUVpeak, and
      contrast-to-noise ratio (CNR) were made for 46 lung and 19 liver lesions. To
      evaluate image noise, the SUV standard deviation was measured in healthy lung and
      liver tissue and in the phantom background. Finally, subjective image quality of
      patient exams was scored on a 5 point scale by four radiologists. Results: In the
      phantom, EMDB increased SUVmax/SUVpeak over SWB but to a lesser extent than the
      other reconstruction methodologies. The RCNR for EMDB however was higher than all
      other reconstructions (0.68 EMDB > 0.54 HDC > 0.41 PBGmax > 0.31 PBGave). Similar
      results were seen in patient studies. The SUVmax/SUVpeak were higher by
      19.3/11.1% EMDB, 21.6/13.9% HDC, 22.8/12.8% PBGave, and 45.6/26.8% PBGmax
      compared to SWB. Lung/liver noise increased EMDB (3/15%), HDC (35/56%), PBGave
      (100/170%), and PBGmax (146/219%). CNR increased in lung/liver tumors only for
      EMDB (18/13%), and decreased for HDC (-14/-23%), PBGave (-39/-63%), and PBGmax (
      18/-46%). Average radiologist scores of image quality were SWB (4.0 +/- 0.8) >
      EMDB (3.7 +/- 1.0) > HDC (3.1 +/- 1.0) > PBG (1.5 +/- 0.7). Conclusion: The EMDB
      algorithm had the least increase in image noise, improved lesion CNR, and had the
      highest overall image quality score.

PMID- 30115692
TI  - In Vivo Estimation of Oncolytic Virus Populations within Tumors.
AB  - The use of replication-competent viruses as oncolytic agents is rapidly
      expanding, with several oncolytic viruses approved for cancer therapy. As
      responses to therapy are highly variable, understanding the dynamics of therapy
      is critical for optimal application of virotherapy in practice. Although
      mathematical models have been developed to understand the dynamics of tumor
      virotherapy, a scarcity of in vivo data has made difficult parametrization of
      these models. To tackle this problem, we studied the in vitro and in vivo spread
      of two oncolytic measles viruses that induce expression of the sodium iodide
      symporter (NIS) in cells. NIS expression enabled infected cells to concentrate
      radioactive isotopes that could be reproducibly and quantitatively imaged using
      SPECT/CT. We observed a strong linear relationship in vitro between infectious
      virus particles, viral N and NIS gene expression, and radioactive isotope uptake.
      In vivo radioisotope uptake was highly correlated with viral N and NIS gene
      expression. Similar expression patterns between viral N and NIS gene expression
      in vitro and in vivo implied that the oncolytic virus behaved similarly in both
      scenarios. Significant titers of viable virus were consistently isolated from
      tumors explanted from mice that had been injected with oncolytic measle viruses.
      We observed a weaker but positive in vivo relationship between radioisotope
      uptake and the viable virus titer recovered from tumors; this was likely due to
      anisotropies in the viral distribution in vivo These data suggest that methods
      that enable quantitation of in vivo anisotropies are required for continuing
      development of oncolytic virotherapy.Significance: These findings address a
      fundamental gap in our knowledge of oncolytic virotherapy by presenting
      technology that gives insight into the behavior of oncolytic viruses in vivo
      Cancer Res; 78(20); 5992-6000. (c)2018 AACR.

PMID- 30115693
TI  - IFNgamma PET Imaging as a Predictive Tool for Monitoring Response to Tumor
      Immunotherapy.
AB  - IFNgamma is an attractive target for imaging active antitumor immunity due to its
      function in the T-cell signaling axis. Here, we test an IFNgamma immuno-PET
      (immunoPET) probe for its capacity to identify adaptive immunotherapy response
      after HER2/neu vaccination in both spontaneous salivary and orthotopic neu+ mouse
      mammary tumors. IFNgamma immunoPET detected elevated cytokine levels in situ
      after vaccination, which inversely correlated with tumor growth rate, an
      indicator of response to therapy. In a model of induced T-cell anergy where CD8 T
      cells infiltrate the tumor, but upregulate PD-1, IFNgamma tracer uptake was
      equivalent to isotype control, illustrating a lack of antitumor T-cell activity.
      The IFNgamma immunoPET tracer detected IFNgamma protein sequestered on the
      surface of tumor cells, likely in complex with the IFNgamma receptor, which may
      explain imaging localization of this soluble factor in vivo Collectively, we find
      that the activation status of cytotoxic T cells is annotated by IFNgamma
      immunoPET, with reduced off-target binding to secondary lymphoid tissues compared
      with imaging total CD3+ tumor-infiltrating lymphocytes. Targeting of soluble
      cytokines such as IFNgamma by PET imaging may provide valuable noninvasive
      insight into the function of immune cells in situ Significance: This study
      presents a novel approach to monitor therapeutic outcomes via IFNgamma-targeted
      positron emission tomography. Cancer Res; 78(19); 5706-17. (c)2018 AACR.

PMID- 30115691
TI  - ErbB3 Targeting Enhances the Effects of MEK Inhibitor in Wild-Type BRAF/NRAS
      Melanoma.
AB  - MEK-ERK1/2 signaling is elevated in melanomas that are wild-type for both BRAF
      and NRAS (WT/WT), but patients are insensitive to MEK inhibitors. Stromal-derived
      growth factors may mediate resistance to targeted inhibitors, and optimizing the
      use of targeted inhibitors for patients with WT/WT melanoma is a clinical unmet
      need. Here, we studied adaptive responses to MEK inhibition in WT/WT cutaneous
      melanoma. The Cancer Genome Atlas data set and tumor microarray studies of WT/WT
      melanomas showed that high levels of neuregulin-1 (NRG1) were associated with
      stromal content and ErbB3 signaling. Of growth factors implicated in resistance
      to targeted inhibitors, NRG1 was effective at mediating resistance to MEK
      inhibitors in patient-derived WT/WT melanoma cells. Furthermore, ErbB3/ErbB2
      signaling was adaptively upregulated following MEK inhibition. Patient-derived
      cancer-associated fibroblast studies demonstrated that stromal-derived NRG1
      activated ErbB3/ErbB2 signaling and enhanced resistance to a MEK inhibitor. ErbB3
      and ErbB2-neutralizing antibodies blocked the protective effects of NRG1 in
      vitro and cooperated with the MEK inhibitor to delay tumor growth in both cell
      line and patient-derived xenograft models. These results highlight tumor
      microenvironment regulation of targeted inhibitor resistance in WT/WT melanoma
      and provide a rationale for combining MEK inhibitors with anti-ErbB3/ErbB2
      antibodies in patients with WT/WT cutaneous melanoma, for whom there are no
      effective targeted therapy options.Significance: This work suggests a mechanism
      by which NRG1 regulates the sensitivity of WT NRAS/BRAF melanomas to MEK
      inhibitors and provides a rationale for combining MEK inhibitors with anti
      ErbB2/ErbB3 antibodies in these tumors. Cancer Res; 78(19); 5680-93. (c)2018
      AACR.

PMID- 30115695
TI  - RAS-MAPK Pathway-Driven Tumor Progression Is Associated with Loss of CIC and
      Other Genomic Aberrations in Neuroblastoma.
AB  - Mutations affecting the RAS-MAPK pathway frequently occur in relapsed
      neuroblastoma tumors, which suggests that activation of this pathway is
      associated with a more aggressive phenotype. To explore this hypothesis, we
      generated several model systems to define a neuroblastoma RAS-MAPK pathway
      signature. Activation of this pathway in primary tumors indeed correlated with
      poor survival and was associated with known activating mutations in ALK and other
      RAS-MAPK pathway genes. Integrative analysis showed that mutations in PHOX2B,
      CIC, and DMD were also associated with an activated RAS-MAPK pathway. Mutation of
      PHOX2B and deletion of CIC in neuroblastoma cell lines induced activation of the
      RAS-MAPK pathway. This activation was independent of phosphorylated ERK in CIC
      knockout systems. Furthermore, deletion of CIC caused a significant increase in
      tumor growth in vivo These results show that the RAS-MAPK pathway is involved in
      tumor progression and establish CIC as a powerful tumor suppressor that functions
      downstream of this pathway in neuroblastoma.Significance: This work identifies
      CIC as a powerful tumor suppressor affecting the RAS-MAPK pathway in
      neuroblastoma and reinforces the importance of mutation-driven activation of this
      pathway in cancer. Cancer Res; 78(21); 6297-307. (c)2018 AACR.

PMID- 30115694
TI  - Transcriptomics and Transposon Mutagenesis Identify Multiple Mechanisms of
      Resistance to the FGFR Inhibitor AZD4547.
AB  - In human cancers, FGFR signaling is frequently hyperactivated by deregulation of
      FGF ligands or by activating mutations in the FGFR receptors such as gene
      amplifications, point mutations, and gene fusions. As such, FGFR inhibitors are
      considered an attractive therapeutic strategy for patients with mutations in FGFR
      family members. We previously identified Fgfr2 as a key driver of invasive
      lobular carcinoma (ILC) in an in vivo insertional mutagenesis screen using the
      Sleeping Beauty transposon system. Here we explore whether these FGFR-driven ILCs
      are sensitive to the FGFR inhibitor AZD4547 and use transposon mutagenesis in
      these tumors to identify potential mechanisms of resistance to therapy. Combined
      with RNA sequencing-based analyses of AZD4547-resistant tumors, our in vivo
      approach identified several known and novel potential resistance mechanisms to
      FGFR inhibition, most of which converged on reactivation of the canonical MAPK
      ERK signaling cascade. Observed resistance mechanisms included mutations in the
      tyrosine kinase domain of FGFR2, overexpression of MET, inactivation of RASA1,
      and activation of the drug-efflux transporter ABCG2. ABCG2 and RASA1 were
      identified only from de novo transposon insertions acquired during AZD4547
      treatment, demonstrating that insertional mutagenesis in mice is an effective
      tool for identifying potential mechanisms of resistance to targeted cancer
      therapies.Significance: These findings demonstrate that a combined approach of
      transcriptomics and insertional mutagenesis in vivo is an effective method for
      identifying potential targets to overcome resistance to therapy in the clinic.
      Cancer Res; 78(19); 5668-79. (c)2018 AACR.

PMID- 30115696
TI  - Oxygen-Enhanced and Dynamic Contrast-Enhanced Optoacoustic Tomography Provide
      Surrogate Biomarkers of Tumor Vascular Function, Hypoxia, and Necrosis.
AB  - Measuring the functional status of tumor vasculature, including blood flow
      fluctuations and changes in oxygenation, is important in cancer staging and
      therapy monitoring. Current clinically approved imaging modalities suffer long
      procedure times and limited spatiotemporal resolution. Optoacoustic tomography
      (OT) is an emerging clinical imaging modality that may overcome these challenges.
      By acquiring data at multiple wavelengths, OT can interrogate hemoglobin
      concentration and oxygenation directly and resolve contributions from injected
      contrast agents. In this study, we tested whether two dynamic OT techniques,
      oxygen-enhanced (OE) and dynamic contrast-enhanced (DCE)-OT, could provide
      surrogate biomarkers of tumor vascular function, hypoxia, and necrosis. We found
      that vascular maturity led to changes in vascular function that affected tumor
      perfusion, modulating the DCE-OT signal. Perfusion in turn regulated oxygen
      availability, driving the OE-OT signal. In particular, we demonstrate for the
      first time a strong per-tumor and spatial correlation between imaging biomarkers
      derived from these in vivo techniques and tumor hypoxia quantified ex vivo Our
      findings indicate that OT may offer a significant advantage for localized imaging
      of tumor response to vascular-targeted therapies when compared with existing
      clinical DCE methods.Significance: Imaging biomarkers derived from optoacoustic
      tomography can be used as surrogate measures of tumor perfusion and hypoxia,
      potentially yielding rapid, multiparametric, and noninvasive cancer staging and
      therapeutic response monitoring in the clinic.Graphical Abstract:
      http://cancerres.aacrjournals.org/content/canres/78/20/5980/F1.large.jpg Cancer
      Res; 78(20); 5980-91. (c)2018 AACR.

PMID- 30115697
TI  - Tailoring Chemotherapy for the African-Centric S47 Variant of TP53.
AB  - The tumor suppressor TP53 is the most frequently mutated gene in human cancer and
      serves to restrict tumor initiation and progression. Single-nucleotide
      polymorphisms (SNP) in TP53 and p53 pathway genes can have a marked impact on p53
      tumor suppressor function, and some have been associated with increased cancer
      risk and impaired response to therapy. Approximately 6% of Africans and 1% of
      African Americans express a p53 allele with a serine instead of proline at
      position 47 (Pro47Ser). This SNP impairs p53-mediated apoptosis in response to
      radiation and genotoxic agents and is associated with increased cancer risk in
      humans and in a mouse model. In this study, we compared the ability of wild-type
      (WT) and S47 p53 to suppress tumor development and respond to therapy. Our goal
      was to find therapeutic compounds that are more, not less, efficacious in S47
      tumors. We identified the superior efficacy of two agents, cisplatin and BET
      inhibitors, on S47 tumors compared with WT. Cisplatin caused dramatic decreases
      in the progression of S47 tumors by activating the p53/PIN1 axis to drive the
      mitochondrial cell death program. These findings serve as important proof of
      principle that chemotherapy can be tailored to p53 genotype.Significance: A rare
      African-derived radioresistant p53 SNP provides proof of principle that
      chemotherapy can be tailored to TP53 genotype. Cancer Res; 78(19); 5694-705.
      (c)2018 AACR.

PMID- 30115700
TI  - Extracellular Citrate and Cancer Metabolism-Response.

PMID- 30115699
TI  - CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells
      Letter.

PMID- 30115698
TI  - CD44-Targeting PLGA Nanoparticles Incorporating Paclitaxel and FAK siRNA Overcome
      Chemoresistance in Epithelial Ovarian Cancer.
AB  - Chemotherapy is commonly used in the treatment of ovarian cancer, yet most
      ovarian cancers harbor inherent resistance or develop acquired resistance.
      Therefore, novel therapeutic approaches to overcome chemoresistance are required.
      In this study, we developed a hyaluronic acid-labeled poly(d,l-lactide-co
      glycolide) nanoparticle (HA-PLGA-NP) encapsulating both paclitaxel (PTX) and
      focal adhesion kinase (FAK) siRNA as a selective delivery system against
      chemoresistant ovarian cancer. The mean size and zeta potential of the HA-PLGA-NP
      were 220 nm and -7.3 mV, respectively. Incorporation efficiencies for PTX and FAK
      siRNA in the HA-PLGA-NPs were 77% and 85%, respectively. HA-PLGA-NP showed higher
      binding efficiency for CD44-positive tumor cells as compared with CD44-negative
      cells. HA-PLGA (PTX+FAK siRNA)-NP caused increased cytotoxicity and apoptosis in
      drug-resistant tumor cells. Treatment of human epithelial ovarian cancer tumor
      models HeyA8-MDR (P < 0.001) and SKOV3-TR (P < 0.001) with HA-PLGA (PTX+FAK
      siRNA)-NP resulted in significant inhibition of tumor growth. Moreover, in a drug
      resistant, patient-derived xenograft (PDX) model, HA-PLGA (PTX+FAK siRNA)-NP
      significantly inhibited tumor growth compared with PTX alone (P < 0.002). Taken
      together, HA-PLGA-NP acts as an effective and selective delivery system for both
      the chemotherapeutic and the siRNA in order to overcome chemoresistance in
      ovarian carcinoma.Significance: These findings demonstrate the efficacy of a
      novel, selective, two-in-one delivery system to overcome chemoresistance in
      epithelial ovarian cancer. Cancer Res; 78(21); 6247-56. (c)2018 AACR.

PMID- 30115701
TI  - Extracellular Citrate and Cancer Metabolism-Letter.

PMID- 30115702
TI  - CD39 Expression Defines Cell Exhaustion in Tumor-Infiltrating CD8+ T Cells
      Response.

PMID- 30115704
TI  - Fundamental Mechanisms of Immune Checkpoint Blockade Therapy.
AB  - Immune checkpoint blockade is able to induce durable responses across multiple
      types of cancer, which has enabled the oncology community to begin to envision
      potentially curative therapeutic approaches. However, the remarkable responses to
      immunotherapies are currently limited to a minority of patients and indications,
      highlighting the need for more effective and novel approaches. Indeed, an
      extraordinary amount of preclinical and clinical investigation is exploring the
      therapeutic potential of negative and positive costimulatory molecules. Insights
      into the underlying biological mechanisms and functions of these molecules have,
      however, lagged significantly behind. Such understanding will be essential for
      the rational design of next-generation immunotherapies. Here, we review the
      current state of our understanding of T-cell costimulatory mechanisms and
      checkpoint blockade, primarily of CTLA4 and PD-1, and highlight conceptual gaps
      in knowledge.Significance: This review provides an overview of immune checkpoint
      blockade therapy from a basic biology and immunologic perspective for the cancer
      research community. Cancer Discov; 8(9); 1069-86. (c)2018 AACR.

PMID- 30115705
TI  - DeepLesion Dataset Aids Tumor Detection.
AB  - Historically, researchers interested in developing automated methods to detect
      tumors in medical images have been hampered by the small size of the image
      collections available for training models using a deep-learning approach.
      Recently, however, NIH researchers unveiled DeepLesion, a free collection of over
      30,000 annotated CT scans that scientists can use for this purpose.

PMID- 30115703
TI  - Targeting the MTF2-MDM2 Axis Sensitizes Refractory Acute Myeloid Leukemia to
      Chemotherapy.
AB  - Deep sequencing has revealed that epigenetic modifiers are the most mutated genes
      in acute myeloid leukemia (AML). Thus, elucidating epigenetic dysregulation in
      AML is crucial to understand disease mechanisms. Here, we demonstrate that metal
      response element binding transcription factor 2/polycomblike 2 (MTF2/PCL2) plays
      a fundamental role in the polycomb repressive complex 2 (PRC2) and that its loss
      elicits an altered epigenetic state underlying refractory AML. Unbiased systems
      analyses identified the loss of MTF2-PRC2 repression of MDM2 as central to, and
      therefore a biomarker for, refractory AML. Thus, immature MTF2-deficient
      CD34+CD38- cells overexpress MDM2, thereby inhibiting p53 that leads to
      chemoresistance due to defects in cell-cycle regulation and apoptosis. Targeting
      this dysregulated signaling pathway by MTF2 overexpression or MDM2 inhibitors
      sensitized refractory patient leukemic cells to induction chemotherapeutics and
      prevented relapse in AML patient-derived xenograft mice. Therefore, we have
      uncovered a direct epigenetic mechanism by which MTF2 functions as a tumor
      suppressor required for AML chemotherapeutic sensitivity and identified a
      potential therapeutic strategy to treat refractory AML.Significance: MTF2
      deficiency predicts refractory AML at diagnosis. MTF2 represses MDM2 in
      hematopoietic cells and its loss in AML results in chemoresistance. Inhibiting
      p53 degradation by overexpressing MTF2 in vitro or by using MDM2 inhibitors in
      vivo sensitizes MTF2-deficient refractory AML cells to a standard induction
      chemotherapy regimen. Cancer Discov; 8(11); 1376-89. (c)2018 AACR. See related
      commentary by Duy and Melnick, p. 1348 This article is highlighted in the In This
      Issue feature, p. 1333.

PMID- 30115706
TI  - Myriad manifestations of infective endocarditis.
AB  - Aneurysmal disease of the visceral arteries is rare, often found incidentally and
      carries significant mortality when ruptured. Of these, superior mesenteric artery
      (SMA) aneurysms represent a small minority of visceral artery aneurysms. This
      case highlights a man in his late 50s who presented to the emergency department
      with right upper quadrant and lower back pain. A CT scan revealed an aneurysm in
      the SMA. Increasing abdominal pain and increasing aneurysmal size with concurrent
      diagnosis of infective endocarditis suggestive of mycotic aneurysm prompted
      urgent treatment. The man was treated successfully by endovascular method.

PMID- 30115707
TI  - Acute biliary pancreatitis masking haemobilia due to a false aneurysm of the
      right hepatic artery after laparoscopic cholecystectomy.
AB  - Laparoscopic cholecystectomy is a commonly performed surgical procedure. The
      postoperative course is often uncomplicated; however, complications like
      infection, biliary leakage, and bleeding and bile duct injury can occur. Here we
      report on a patient with common bile duct obstruction and haemobilia due to a
      false aneurysm of the right hepatic artery after laparoscopic cholecystectomy,
      masked by biliary pancreatitis, complicated by an infarction of the liver after
      embolisation. The aetiology of upper gastrointestinal bleeding greatly varies.
      This case is an uncommon case of gastrointestinal bleeding due to a false
      aneurysm of the right hepatic artery, which was successfully treated.

PMID- 30115708
TI  - Hypertension and severe hypokalaemia associated with ectopic ACTH production.
AB  - Ectopic adrenocorticotropic hormone (ACTH) secretion represents 5%-10% of cases
      of Cushing's syndrome (CS), and approximately 50%-60% of these arise from
      neuroendocrine lung tumours, including small-cell lung cancer (SCLC). We report a
      42-year-old man admitted with hypertension, metabolic alkalosis and severe
      hypokalaemia. On physical examination, centripetal obesity with 'moon face' and
      'buffalo's hump' were identified, and wheezing on left lung was heard. A markedly
      elevated serum cortisol, ACTH and urine free cortisol production supported the
      diagnosis of CS. Chest CT showed a left hilar mass with metastasis to the liver,
      adrenal glands and lymph nodes. Bronchoscopy identified bronchial infiltration by
      SCLC. Treatment with metyrapone and chemotherapy was started. Despite initial
      improvement, progressive clinical deterioration occurred, culminating in death 1
      year after diagnosis. Ectopic ACTH secretion is uncommon but should be suspected
      in patients with severe hypokalaemia, hypertension and metabolic alkalosis,
      especially in the context of lung cancer.

PMID- 30115709
TI  - Silicone oil mimicking pathology on CT imaging.
AB  - An 81-year-old man was taken to Accident & Emergency after a fall. CT brain
      imaging demonstrated a well-defined, homogenous, hyperdense mass in the posterior
      segment of the left eye. Reported as vitreous haemorrhage, an urgent
      ophthalmological assessment was instigated.Detailed history revealed previous
      vitreoretinal procedures for multiple retinal detachments. Ophthalmological
      examination confirmed presence of silicone oil in this eye.The appearance of
      silicone oil in the eye has become an increasingly prevalent finding given its
      continued use in complex vitreoretinal procedures since 1962. Clinicians
      regularly interpreting orbital, facial and brain imaging need to be aware of
      these imaging appearances to prevent diagnostic confusion.

PMID- 30115710
TI  - Use of an onlay corneal lamellar graft for brittle cornea syndrome.
AB  - Brittle cornea syndrome (BCS1 OMIM #229200, BCS2 #614170) is a rare autosomal
      recessive condition characterised by diffuse thinning and fragility of the
      cornea. Affected individuals are at risk of globe rupture and blindness after
      relatively minor eye trauma. We describe a 9-year-old girl with BCS1, already
      blind in one eye following trauma, who had a 14 mm diameter corneoscleral onlay
      graft to her contralateral eye to reduce gross irregular corneal astigmatism and
      potentially to reduce further risk from accidental injury. Although there was a
      significant initial improvement in the unaided visual acuity, there was
      subsequent visual loss from secondary glaucoma. In addition, despite the onlay
      graft, an acute corneal hydrops developed approximately 2 years following
      surgery, suggesting that in BCS1, corneal tissue degeneration or resorption
      continues despite external support. Finally, because secondary glaucoma is not a
      feature of BCS1, we speculate that the onlay graft may have reduced aqueous
      outflow by compression of the thinned sclera.

PMID- 30115711
TI  - Oesophageal-pleural fistulation identified through repeated malpositioning of
      nasogastric tubes.
AB  - Two previously fit and healthy males with acute onset dyspnoea and respiratory
      failure required invasive ventilation for respiratory failure. Insertion and
      correct positioning of nasogastric tubes (NGT) proved to be difficult repeatedly
      in both cases over the course of a number of days. Repeated imaging found NGT
      tips sited in varied, atypical positions including extension into the
      hemithoraces. Delineation of repeated malpositioned NGTs identified oesophageal
      perforations in the case of both patients, one with fistulation into the right
      pleura and the other into the left pleura. Both patients developed an empyema
      ipsilateral to the side of fistulation. Both patients died, with subsequent
      postmortems concluding one patient to have experienced a spontaneous out-of
      hospital oesophageal perforation, and the second patient's perforation developing
      as a consequence of a distal oesophageal squamous cell carcinoma. These two cases
      highlight the importance of questioning the possibility of underlying oesophageal
      pathology promptly if repeated NGT insertions are unsuccessful or imaging reveals
      unusual transit paths of NGTs.

PMID- 30115712
TI  - Wandering spleen caused by subcapsular haemorrhage.

PMID- 30115713
TI  - Cerebral air embolism from a Central Venous Catheter: A timely reminder of the
      importance of rapid diagnosis.
AB  - Cerebral air embolism (CAE) is a rare, avoidable and potentially fatal iatrogenic
      complication. Here, we report a case of CAE associated with a central venous
      catheter in the internal jugular vein that resulted in neurological deficits and
      generalised epileptic seizures. A 64-year-old man admitted for fasciotomy for
      compartment syndrome developed CAE with left-sided neurological deficits. The
      suspected origin was retrograde air flow from the right internal jugular venous
      catheter. The air spontaneously resorbed without the need for specific therapy,
      and he made a good recovery. CAE is an infrequent iatrogenic complication that
      requires prompt diagnosis to avoid significant morbidity and mortality. This case
      serves as a timely reminder that adverse outcome such as stroke, seizures or
      death can be avoided by a high index of suspicion and prompt diagnosis.
      Hyperbaric oxygen is the prime therapeutic measure, but high-quality evidence on
      its clinical value is lacking.

PMID- 30115714
TI  - Small bowel adenocarcinoma in a patient with Lynch syndrome.
AB  - A 49-year-old male patient, morbidly obese, with a background of Lynch syndrome
      and subtotal colectomy for colon cancer in 2007, presented with severe abdominal
      pain in December 2015. Since then, the patient presented multiple times to the
      emergency department with severe diffuse abdominal pain. After extensive
      examination, no clear cause for the pain was identified and it was thought to be
      secondary to adhesions, incisional hernias and psychological. Examinations via
      radiological imaging were challenging due to body habitus and claustrophobia. In
      September 2017, the patient was admitted from outpatient clinic with severe
      abdominal pain, weight loss and anaemia. A CT scan of abdomen and pelvis
      demonstrated a dilated jejunal loop with a possible tumour. Surgery confirmed a
      small bowel tumour and, nearly 2 years after the initial presentation, the
      patient was diagnosed with adenocarcinoma of the jejenum. The patient underwent
      surgical excision and his symptoms subsided.

PMID- 30115715
TI  - Keratinising squamous metaplasia of the bladder.
AB  - Keratinising squamous metaplasia of the bladder is a very rare entity that
      carries a risk of progression to malignancy. We present a case of a 62-year-old
      man found to have the condition and discuss the management dilemma with a review
      of the literature.

PMID- 30115716
TI  - Adult-onset Still's disease with haemorrhagic pericarditis and tamponade preceded
      by acute Lyme disease.
AB  - A 61-year-old Caucasian man presented with a fever of unknown origin, a transient
      erythematous rash on his right upper extremity and chest pressure after being
      treated for erythema migrans (Lyme disease). Echocardiogram demonstrated a large
      pericardial effusion with tamponade. He underwent pericardiostomy with tube
      placement. Workup for infectious and malignant etiologies was negative. Histology
      of the pericardium showed acute on chronic fibrinous haemorrhagic pericarditis.
      The patient met criteria for adult-onset Still's disease. Symptoms resolved
      following treatment with methylprednisolone and anakinra. We believe this is the
      first case of adult-onset Still's disease precipitated by acute Lyme disease.

PMID- 30115717
TI  - Rapid and life-threatening heart failure induced by pazopanib.
AB  - A 70-year-old man with history of stage IV renal cell carcinoma, chronic atrial
      fibrillation on warfarin, coronary artery disease status post-percutaneous
      coronary intervention resulting in an ischaemic cardiomyopathy with left
      ventricular ejection fraction of 40%-45%, presented with shortness of breath 10
      days after starting pazopanib. Within the first week of starting pazopanib, the
      patient developed fatigue and progressive dyspnoea on exertion. His symptoms
      quickly worsened and he had compromised mental status. He was transferred to the
      intensive care unit (ICU) and intubated due to continued respiratory distress. He
      was found to be in cardiogenic shock and was started on inotropic support with
      dobutamine and norepinephrine. With maximum support, the patient was slowly
      weaned off vasopressors and was successfully extubated on ICU day 9. His hospital
      stay lasted 29 days with management of multiple medical complications, and he was
      eventually discharged to a rehabilitation facility.

PMID- 30115718
TI  - Nitrofurantoin: friend or foe?
AB  - Nitrofurantoin remains the gold standard treatment of uncomplicated cystitis as
      well as prophylactic treatment of recurrent urinary tract infections. Drug
      induced hepatotoxicity presents in acute (3 in 1 000 000) and chronic (1 in 1500)
      forms. We present a patient with acute liver failure after 5 days of treatment. A
      69-year-old man admitted for chronic obstructive pulmonary disease exacerbation 5
      days into treatment for cystitis with nitrofurantoin. On admission he was noted
      to be jaundiced with elevated liver enzymes and normal international normalised
      ratio. Investigation for infectious, autoimmune and cholestatic causes of
      hepatotoxicity was negative. The patient improved after discontinuation of the
      drug and 10 days of methylprednisolone. There are scant data on acute liver
      failure in the setting of short-term nitrofurantoin administration. The mechanism
      of toxicity remains unclear, but is hypothesised to be an autoimmune process in
      which steroids may play a role in treatment. Diagnosis is one of exclusion as the
      only definitive method of diagnosis is rechallenge.

PMID- 30115719
TI  - Bilateral cataracts as the presenting feature of type 1 diabetes in an 11-year
      old girl.
AB  - Paediatric cataracts can present a diagnostic dilemma to ophthalmologists. Next
      generation DNA sequencing (NGS) has been promoted as a tool to expedite the
      diagnosis of an underlying cause in such cases.1 The authors present an unusual
      case of bilateral cataracts in an 11-year-old girl as the first presenting
      feature of new type 1 diabetes mellitus. Prompt diagnosis and subsequent
      management of this potentially life-threatening condition were achieved through
      careful history taking and targeted biochemical testing. The authors feel this
      case highlights the significance of simple measures such as thorough history
      taking in the assessment of paediatric cataracts. It is important that these
      skills are not lost through the availability of clinical tools such as NGS.

PMID- 30115720
TI  - Tension haemothorax from a bleeding branch of the renal artery following isolated
      penetrating thoracic trauma: a rare presentation.
AB  - A 27-year-old man presented to a major trauma centre with two posterolateral
      thoracic stab injuries over the right scapula and thoracoabdominal junction. He
      was tachycardic and hypotensive with a chest X-ray revealing a large right-sided
      tension haemothorax, requiring insertion of two intercostal chest drains. A
      subsequent CT scan demonstrated a grade 4 right kidney laceration with active
      back bleeding from a renal artery branch, through a right diaphragmatic defect,
      into the pleural cavity. Embolisation of the feeding renal vessel controlled the
      bleeding and avoided the need for a nephrectomy. The patient required subsequent
      video-assisted thoracoscopic evacuation of the haemothorax and diaphragmatic
      repair, confirming that there was no associated lung or major vessel injury. A
      ureteric stent was ultimately inserted to manage a persistent urinary leak. This
      case highlights a rare cause for a common traumatic presentation and the need for
      a multidisciplinary approach in effective management of complex, multiorgan
      trauma.

PMID- 30115721
TI  - What are the odds? Prostate metastases to ureter and peritoneum.
AB  - In patients with prostate cancer, metastases mostly develop in bone, lung, liver,
      pleura and adrenal glands. Prostate carcinoma metastases to the ureter are very
      rare, and the peritoneum is an even rarer site of prostate metastases. We present
      two cases of ureteral metastases of prostate cancer, of which one patient also
      developed malignant ascites and peritoneal metastases. An overview of the
      literature on these metastatic sites is also provided. Both patients presented
      with hydronephrosis and a ureteral mass. Biopsies of the masses were taken, which
      showed the presence of prostate carcinoma metastases. The first patient was
      treated with chemotherapy but was diagnosed with progressive disease and died 3
      years later. The second patient was diagnosed with pathology-confirmed peritoneal
      metastases 8 months later. He died 2 years after presentation with
      hydronephrosis.

PMID- 30115722
TI  - Burkitt's neurolymphomatosis of the trigeminal nerve.

PMID- 30115723
TI  - Coeliac artery dissection as a rare manifestation of Behcet's disease.
AB  - Behcet's disease is a multisystemic vasculitis. Arterial involvement in the form
      of acute dissection is rare. A 42-year-old Lebanese man with Behcet's disease
      presented with severe abdominal pain. On exam, blood pressure was 162/104 mm Hg,
      and he exhibited epigastric tenderness. CT angiogram demonstrated an acute
      dissection of the coeliac artery trunk, common hepatic artery and proper hepatic
      arteries, with asymmetric thickening of the proximal left subclavian artery and
      circumferential thickening of the abdominal infrarenal aorta suggestive of
      vasculitis. Treatment included intravenous clevidipine, nitroprusside and
      methylprednisolone, which transitioned to oral metoprolol, amlodipine and
      prednisone. He responded well. Arterial dissections have been described with
      Behcet's. We report a coeliac artery aneurysm in association with a flare of
      Behcet's disease. Arterial wall inflammation combined with the sheering forces of
      hypertension likely predisposes to arterial dissection.

PMID- 30115725
TI  - How did a prosthetic femoral head migrate to the mesorectum?

PMID- 30115724
TI  - Infarcted accessory spleen masquerading as a mesenteric cyst.
AB  - An accessory spleen is a rare entity which is usually asymptomatic. When
      symptomatic, it presents as an acute abdomen, with either torsion, rupture or
      haemorrhage. We present the case of a 20-year-old man who presented with chronic
      lower abdominal pain since 3 months and a lump in the left lower quadrant. On
      clinical examination and investigations, the lump was diagnosed as a mesenteric
      cyst, and an uncomplicated laparoscopic excision was performed. The postoperative
      histopathological examination reported it as an infarcted accessory spleen.

PMID- 30115726
TI  - Eight-year follow-up of resurfacing hemiarthroplasty for advanced glenohumeral
      osteoarthritis following total acromionectomy.
AB  - Total acromionectomy is now a largely historical procedure due to a number of
      biomechanical sequelae caused by defunctioning of the deltoid, although its
      overall effect on joint kinematics is uncertain. This presents a challenge when
      considering arthroplasty for subsequent glenohumeral arthritis. We report on
      successful management of such a case, treated with resurfacing hemiarthroplasty
      57 years following acromionectomy. The patient continues to enjoy excellent
      functional outcome of the shoulder at 8 years after arthroplasty.

PMID- 30115727
TI  - Takotsubo cardiomyopathy in a patient with bipolar disorder.

PMID- 30115728
TI  - Giant urinary bladder (11 000 mL in volume) with bilateral lower limb oedema: an
      unusual cause of inferior vena cava obstruction.

PMID- 30115729
TI  - Management of sigmoid perforation from chronic constipation and manual
      disimpaction.

PMID- 30115730
TI  - Delayed presentation of post-traumatic pseudo-phacocoele.

PMID- 30115731
TI  - Hypertonic Saline in Bronchiolitis and Type I Error: A Trial Sequential Analysis.
AB  - : : media-1vid110.1542/5799873875001PEDS-VA_2018-1144Video Abstract BACKGROUND
      AND OBJECTIVES: Meta-analyses of nebulized hypertonic saline (HS) for acute viral
      bronchiolitis have yielded disparate conclusions. Trial sequential analysis (TSA)
      is a novel method designed to account for potential sources of error in
      conventional meta-analysis. We sought to use TSA to determine if the existing
      literature base is sufficient to draw firm conclusions about the effectiveness of
      HS in bronchiolitis. METHODS: We used the cohort of studies identified in
      previously published conventional meta-analyses. Included studies were those in
      which authors compared treatment with HS versus normal saline (or supportive
      care) in children with bronchiolitis to reduce hospital length of stay (LOS) or
      hospitalizations. TSA results are used to provide a required information size and
      monitoring boundaries for statistical significance. RESULTS: For the LOS outcome,
      17 studies including 1866 patients analyzed in which authors used conventional
      meta-analysis reveal a statistically significant benefit (mean difference = -0.41
      days; 95% confidence interval = -0.07 to -0.75); however, TSA suggests that those
      conclusions are premature because of failure to reach the adequate information
      size of 2665 individuals. For the risk of hospitalization outcome, 8 studies
      including 1728 patients analyzed in which authors used conventional meta-analysis
      reveal a reduction in the relative risk of hospitalization (relative risk = 0.86;
      95% confidence interval = 0.76 to 0.98); however, TSA suggests these conclusions
      are premature because of failure to reach the adequate information size of 4770.
      Both LOS and hospitalization results from conventional meta-analysis would be
      considered potentially false-positives by TSA. CONCLUSIONS: TSA reveals that
      concluding benefit from HS for children with bronchiolitis potentially represents
      type I error.

PMID- 30115732
TI  - Recruitment and Retention of Community Preceptors.
AB  - BACKGROUND: Recruiting and retaining community-based pediatricians for teaching
      medical students has been explored through the lens of preceptors and educational
      leaders. The purpose of this study was to explore the perspective of pediatric
      department chairs, a key stakeholder group charged with maintaining teaching
      capacity among a faculty. METHODS: In 2015, members of the Association of Medical
      School Pediatric Department Chairs and Council on Medical Student Education in
      Pediatrics joint task force disseminated a 20-item survey to pediatric department
      chairs in the United States and Canada. Topics included demographics, incentives
      offered to community pediatricians, and the perceived value and feasibility of
      such incentives. Data were analyzed using descriptive statistics and chi2 to
      compare categorical variables. RESULTS: Pediatric department chairs from 92 of
      145 (63% response rate) medical schools returned the survey. Sixty-seven percent
      reported difficulty recruiting or retaining preceptors, and 51% reported high
      reliance on preceptors for the ambulatory portion of the pediatrics clerkship.
      Almost all (92%) cited competition from other programs for the services of
      community preceptors. The provision of incentives was correlated with perceived
      feasibility (R2 = 0.65) but not their perceived value (R2 = 0.12). Few (21%)
      chairs reported providing financial compensation to preceptors. The provision of
      compensation was not related to reliance but did vary significantly by
      geographical region (P < .001). CONCLUSIONS: Pediatric departments rely heavily
      on community-based pediatricians but face competition from internal and external
      training programs. The perspective of department chairs is valuable in weighing
      interventions to facilitate continued recruitment and retention of community
      preceptors.

PMID- 30115733
TI  - New Method, Same Answer: We Do Not Know if Hypertonic Saline Helps Bronchiolitis.

PMID- 30115734
TI  - A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus nab-Paclitaxel and
      Gemcitabine in Advanced Solid Tumors.
AB  - LESSONS LEARNED: Itacitinib in combination with nab-paclitaxel plus gemcitabine
      demonstrated an acceptable safety profile with clinical activity in patients with
      advanced solid tumors including pancreatic cancer.The results support future
      studies of itacitinib as a component of combination regimens with other
      immunologic and targeted small molecule anticancer agents. BACKGROUND: Cytokine
      mediated signaling via JAK/STAT is central to tumor growth, survival, and
      systemic inflammation, which is associated with cancer cachexia, particularly in
      pancreatic cancer. Because of their centrality in the pathogenesis of cancer
      cachexia and progression, JAK isozymes have emerged as promising therapeutic
      targets. Preclinical studies have demonstrated antiproliferative effects of
      JAK/STAT pathway inhibition in both in vitro and in vivo models of cancer,
      including pancreatic cancer. METHODS: This phase Ib/II dose-optimization study
      assessed itacitinib, a selective JAK1 inhibitor, combined with nab-paclitaxel
      plus gemcitabine in adults with treatment-naive advanced/metastatic disease (Part
      1) or pancreatic adenocarcinoma (Parts 2/2A; NCT01858883). Starting doses (Part
      1) were itacitinib 400 mg, nab-paclitaxel 125 mg/m2, and gemcitabine 1,000 mg/m2.
      Additional dose levels incorporated were granulocyte colony-stimulating factor,
      de-escalations of itacitinib to 300 mg once daily (QD), nab-paclitaxel to 100
      mg/m2, and gemcitabine to 750 mg/m2. RESULTS: Among 55 patients in Part 1, 6
      developed seven hematologic dose-limiting toxicities (Cycle 1). Itacitinib 300 mg
      plus nab-paclitaxel 125 mg/m2 and gemcitabine 1,000 mg/m2 was tolerated and
      expanded in Part 2. Treatment discontinuation and grade 3/4 neutropenia rates
      prompted itacitinib de-escalation to 200 mg QD in Part 2A. The most common grade
      3/4 toxicities were fatigue and neutropenia. Partial responses occurred across
      all itacitinib doses and several tumor types (overall response rate, 24%).
      CONCLUSION: Itacitinib plus chemotherapy demonstrated acceptable safety and
      clinical activity in patients with advanced solid tumors including pancreatic
      cancers. This study was terminated early (sponsor's decision) based on negative
      phase III results for a JAK1/2 inhibitor in previously treated advanced
      pancreatic cancer.

PMID- 30115735
TI  - FDA Approval Summary: Midostaurin for the Treatment of Advanced Systemic
      Mastocytosis.
AB  - : In April 2017, the U.S. Food and Drug Administration granted regular approval
      to midostaurin for the treatment of adult patients with aggressive systemic
      mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm
      (SM-AHN), or mast cell leukemia (MCL). Approval was based on results from
      CPKC412D2201, a single-arm trial of midostaurin (100 mg orally twice daily) in
      previously treated or untreated patients. For the patients with ASM and SM-AHN,
      efficacy was established on the basis of confirmed complete remission (CR) plus
      incomplete remission (ICR) by modified Valent criteria with six cycles of
      midostaurin. There were no CRs reported; ICR was achieved by 6 of 16 patients
      (38%; 95% confidence interval [CI]: 15%-65%) with ASM and by 9 of 57 patients
      (16%; 95% CI: 7%-28%) with SM-AHN. Within the follow-up period, the median
      duration of response was not reached for the patients with ASM (range, 12.1+ to
      36.8+ months) or with SM-AHN (range, 6.6+ to 52.1+ months). For the patients with
      MCL, efficacy was established on the basis of confirmed CR using modified 2013
      International Working Group-Myeloproliferative Neoplasms Research and Treatment
      European Competence Network on Mastocytosis criteria. Of 21 patients with MCL, 1
      (5%) achieved a CR. Of 142 patients with SM evaluated for safety, 56% had dose
      modifications for toxicity, and 21% discontinued treatment due to a toxicity.
      Over 50% reported nausea, vomiting, or diarrhea, and >=30% reported edema,
      musculoskeletal pain, fatigue, abdominal pain, or upper respiratory tract
      infection. New or worsening grade >=3 lymphopenia, anemia, thrombocytopenia, or
      neutropenia developed in >=20%. Although midostaurin is an active drug for
      treatment of advanced SM, it is not clear that the optimal dose has been
      identified. IMPLICATIONS FOR PRACTICE: Midostaurin is the only U.S. Food and Drug
      Administration-approved therapy for patients with systemic mastocytosis with
      associated hematological neoplasm and mast cell leukemia and is the only therapy
      approved for patients with aggressive systemic mastocytosis regardless of KIT
      D816V mutation status. Based on response rate and duration, midostaurin has
      meaningful clinical activity in these rare, life-threatening diseases.

PMID- 30115736
TI  - Randomized, Open-Label Phase II Study Comparing Capecitabine-Cisplatin Every 3
      Weeks with S-1-Cisplatin Every 5 Weeks in Chemotherapy-Naive Patients with HER2
      Negative Advanced Gastric Cancer: OGSG1105, HERBIS-4A Trial.
AB  - LESSONS LEARNED: Evidence has suggested that capecitabine-cisplatin is similar or
      possibly superior to S-1-cisplatin in terms of safety and efficacy for Japanese
      patients with advanced gastric cancer (AGC).As far as we are aware, our study is
      the first randomized trial of two regimens consisting of an oral fluoropyrimidine
      plus cisplatin in human epidermal growth receptor 2-negative AGC patients with
      measurable lesions. BACKGROUND: We performed a phase II study to evaluate the
      safety and efficacy of capecitabine plus cisplatin in comparison with S-1 plus
      cisplatin for first-line treatment of human epidermal growth receptor 2 (HER2)
      negative advanced gastric cancer in Japan. METHODS: Eligible patients were
      randomly assigned to receive either capecitabine at 1,000 mg/m2 twice daily for
      14 days plus cisplatin at 80 mg/m2 on day 1 every 3 weeks (n = 43) or S-1 at 40
      60 mg twice daily for 21 days plus cisplatin at 60 mg/m2 on day 8 every 5 weeks
      (n = 41). The primary endpoint of the study was response rate. RESULTS: Response
      rate did not differ significantly between the capecitabine-cisplatin and S-1
      cisplatin groups (53.5% vs. 51.2%, respectively, p > .999). S-1-cisplatin tended
      to confer a better progression-free survival (PFS; median of 5.9 vs. 4.1 months,
      p = .284), overall survival (OS; median of 13.5 vs. 10.0 months, p = .290), and
      time to treatment failure (TTF; median of 4.5 vs. 3.1 months, p = .052) compared
      with capecitabine-cisplatin. Common hematologic toxicities of grade 3 or 4
      included anemia and neutropenia in both groups. However, anorexia, fatigue, and
      hyponatremia of grade 3 or 4 occurred more frequently in the capecitabine
      cisplatin group. CONCLUSION: Capecitabine-cisplatin failed to demonstrate
      superior efficacy compared with S-1-cisplatin. The higher incidence of severe
      adverse events with capecitabine-cisplatin suggests that S-1-cisplatin should
      remain the standard first-line chemotherapy for HER2-negative advanced gastric
      cancer in Japan.

PMID- 30115737
TI  - SUMO Suppresses the Activity of the Jasmonic Acid Receptor CORONATINE
      INSENSITIVE1.
AB  - Plants respond rapidly to sudden environmental cues, often responding prior to
      changes in the hormone levels that coordinate these responses. How this is
      achieved is not fully understood. The integrative role of the phytohormone
      jasmonic acid (JA) relies upon the plant's ability to control the levels of
      JASMONATE ZIM (JAZ) domain-containing repressor proteins. Here, we demonstrate
      that regardless of intrinsic JA levels, Small Ubiquitin-like Modifier (SUMO)
      conjugated JAZ proteins inhibit the JA receptor CORONATINE INSENSITIVE1 (COI1)
      from mediating non-SUMOylated JAZ degradation. The SUMO-deconjugating proteases
      OVERLY TOLERANT TO SALT1 (OTS1) and OTS2 regulate JAZ protein SUMOylation and
      stability. The ots1 ots2 double mutants accumulate SUMOylated and non-SUMOylated
      JAZ repressor proteins but show no change in endogenous JA levels compared with
      wild-type plants. SUMO1-conjugated JAZ proteins bind to COI1 independently of the
      JA mimic coronatine. SUMO inhibits JAZ binding to COI1. We identify the SUMO
      interacting motif in COI1 and demonstrate that this is vital to SUMO-dependent
      inhibition of COI1. Necrotroph infection of Arabidopsis thaliana promotes SUMO
      protease degradation, and this increases JAZ SUMOylation and abundance, which in
      turn inhibits JA signaling. This study reveals a mechanism for rapidly regulating
      JA responses, allowing plants to adapt to environmental changes.

PMID- 30115742
TI  - Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: a comparative
      review.
AB  - Type 2 diabetes (T2D) carries risks of both cardiovascular (CV) (myocardial
      infarction, stroke, and peripheral vascular disease) and microvascular
      (retinopathy/nephropathy/neuropathy) complications. Glucose-lowering is an
      effective strategy for preventing microvascular complications, but the extent to
      which it can reduce CV complications is less certain. Glucagon-like peptide-1
      (GLP-1) agonists are potent glucose-lowering agents but also have potentially
      beneficial effects on other traditional (body weight, blood pressure (BP), and
      LDL cholesterol) and non-traditional risk factors (low grade inflammation and
      endothelial dysfunction). The results of four large CV outcome trials with GLP-1
      agonists are now available. These have compared lixisenatide (ELIXA), liraglutide
      (LEADER), semaglutide (SUSTAIN-6), and long-acting exenatide (EXSCEL) with
      placebo and standard of care over 2-4 years; four others (including with
      dulaglutide and albiglutide) are ongoing. LEADER and SUSTAIN-6 have demonstrated
      reductions in rates of major adverse CV events with active GLP-1 treatment but
      ELIXA and EXSCEL have not. In this review, we discuss the mechanisms by which GLP
      1 receptor agonists act on the CV system and the design and conduct of these
      trials. Contrary to the assertions that (a) all GLP-1 agonists reduce CV disease
      in T2D but to different extents or (b) the magnitude of CV protection is
      predominantly related to glucose-lowering, we argue that CV benefit is specific
      to agents that provide longer acting agonism at the GLP-1 receptor. The
      mechanisms involve reduction in body weight and BP, and lowering of LDL
      cholesterol and glucose, but pleiotropic effects-including suppression of low
      grade inflammation, vasodilation, and natriuresis-are also likely relevant.

PMID- 30115741
TI  - Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the
      lysosome.
AB  - Metabolic programs are crucial for regulatory T (T reg) cell stability and
      function, but the underlying mechanisms that regulate T reg cell metabolism are
      elusive. Here, we report that lysosomal TRAF3IP3 acts as a pivotal regulator in
      the maintenance of T reg cell metabolic fitness. T reg-specific deletion of
      Traf3ip3 impairs T reg cell function, causing the development of inflammatory
      disorders and stronger antitumor T cell responses in mice. Excessive mechanistic
      target of rapamycin complex 1 (mTORC1)-mediated hyper-glycolytic metabolism is
      responsible for the instability of TRAF3IP3-deficient T reg cells.
      Mechanistically, TRAF3IP3 restricts mTORC1 signaling by recruiting the serine
      threonine phosphatase catalytic subunit (PP2Ac) to the lysosome, thereby
      facilitating the interaction of PP2Ac with the mTORC1 component Raptor. Our
      results define TRAF3IP3 as a metabolic regulator in T reg cell stability and
      function and suggest a lysosome-specific mTORC1 signaling mechanism that
      regulates T reg cell metabolism.

PMID- 30115739
TI  - hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with
      lymphatic dysplasia.
AB  - We report the first case of nonimmune hydrops fetalis (NIHF) associated with a
      recessive, in-frame deletion of V205 in the G protein-coupled receptor,
      Calcitonin Receptor-Like Receptor (hCALCRL). Homozygosity results in fetal demise
      from hydrops fetalis, while heterozygosity in females is associated with
      spontaneous miscarriage and subfertility. Using molecular dynamic modeling and in
      vitro biochemical assays, we show that the hCLR(V205del) mutant results in
      misfolding of the first extracellular loop, reducing association with its
      requisite receptor chaperone, receptor activity modifying protein (RAMP),
      translocation to the plasma membrane and signaling. Using three independent
      genetic mouse models we establish that the adrenomedullin-CLR-RAMP2 axis is both
      necessary and sufficient for driving lymphatic vascular proliferation. Genetic
      ablation of either lymphatic endothelial Calcrl or nonendothelial Ramp2 leads to
      severe NIHF with embryonic demise and placental pathologies, similar to that
      observed in humans. Our results highlight a novel candidate gene for human
      congenital NIHF and provide structure-function insights of this signaling axis
      for human physiology.

PMID- 30115740
TI  - Identification of non-mutated neoantigens presented by TAP-deficient tumors.
AB  - Most T cell-based immunotherapies of cancer depend on intact antigen presentation
      by HLA class I molecules (HLA-I). However, defects in the antigen-processing
      machinery can cause downregulation of HLA-I, rendering tumor cells resistant to
      CD8+ T cells. Previously, we demonstrated that a unique category of cancer
      antigens is selectively presented by tumor cells deficient for the peptide
      transporter TAP, enabling a specific attack of such tumors without causing
      immunopathology in mouse models. With a novel combinatorial screening approach,
      we now identify 16 antigens of this category in humans. These HLA-A*02:01
      presented peptides do not derive from the mutanome of cancers, but are of "self"
      origin and therefore constitute universal neoantigens. Indeed, CD8+ T cells
      specific for the leader peptide of the ubiquitously expressed LRPAP1 protein
      recognized TAP-deficient, HLA-Ilow lymphomas, melanomas, and renal and colon
      carcinomas, but not healthy counterparts. In contrast to personalized mutanome
      targeted therapies, these conserved neoantigens and their cognate receptors can
      be exploited for immune-escaped cancers across diverse histological origins.

PMID- 30115738
TI  - A Spatiotemporal DNA Endoploidy Map of the Arabidopsis Root Reveals Roles for the
      Endocycle in Root Development and Stress Adaptation.
AB  - Somatic polyploidy caused by endoreplication is observed in arthropods, molluscs,
      and vertebrates but is especially prominent in higher plants, where it has been
      postulated to be essential for cell growth and fate maintenance. However, a
      comprehensive understanding of the physiological significance of plant
      endopolyploidy has remained elusive. Here, we modeled and experimentally verified
      a high-resolution DNA endoploidy map of the developing Arabidopsis thaliana root,
      revealing a remarkable spatiotemporal control of DNA endoploidy levels across
      tissues. Fitting of a simplified model to publicly available data sets profiling
      root gene expression under various environmental stress conditions suggested that
      this root endoploidy patterning may be stress-responsive. Furthermore, cellular
      and transcriptomic analyses revealed that inhibition of endoreplication onset
      alters the nuclear-to-cellular volume ratio and the expression of cell wall
      modifying genes, in correlation with the appearance of cell structural changes.
      Our data indicate that endopolyploidy might serve to coordinate cell expansion
      with structural stability and that spatiotemporal endoreplication pattern changes
      may buffer for stress conditions, which may explain the widespread occurrence of
      the endocycle in plant species growing in extreme or variable environments.

PMID- 30115743
TI  - Evidence for Majorana bound states in an iron-based superconductor.
AB  - The search for Majorana bound states (MBSs) has been fueled by the prospect of
      using their non-Abelian statistics for robust quantum computation. Two
      dimensional superconducting topological materials have been predicted to host
      MBSs as zero-energy modes in vortex cores. By using scanning tunneling
      spectroscopy on the superconducting Dirac surface state of the iron-based
      superconductor FeTe0.55Se0.45, we observed a sharp zero-bias peak inside a vortex
      core that does not split when moving away from the vortex center. The evolution
      of the peak under varying magnetic field, temperature, and tunneling barrier is
      consistent with the tunneling to a nearly pure MBS, separated from nontopological
      bound states. This observation offers a potential platform for realizing and
      manipulating MBSs at a relatively high temperature.

PMID- 30115744
TI  - Suppressing spatiotemporal lasing instabilities with wave-chaotic microcavities.
AB  - Spatiotemporal instabilities are widespread phenomena resulting from complexity
      and nonlinearity. In broad-area edge-emitting semiconductor lasers, the nonlinear
      interactions of multiple spatial modes with the active medium can result in
      filamentation and spatiotemporal chaos. These instabilities degrade the laser
      performance and are extremely challenging to control. We demonstrate a powerful
      approach to suppress spatiotemporal instabilities using wave-chaotic or
      disordered cavities. The interference of many propagating waves with random
      phases in such cavities disrupts the formation of self-organized structures such
      as filaments, resulting in stable lasing dynamics. Our method provides a general
      and robust scheme to prevent the formation and growth of nonlinear instabilities
      for a large variety of high-power lasers.

PMID- 30115746
TI  - MCM2 promotes symmetric inheritance of modified histones during DNA replication.
AB  - During genome replication, parental histones are recycled to newly replicated DNA
      with their posttranslational modifications (PTMs). Whether sister chromatids
      inherit modified histones evenly remains unknown. We measured histone PTM
      partition to sister chromatids in embryonic stem cells. We found that parental
      histones H3-H4 segregate to both daughter DNA strands with a weak leading-strand
      bias, skewing partition at topologically associating domain (TAD) borders and
      enhancers proximal to replication initiation zones. Segregation of parental
      histones to the leading strand increased markedly in cells with histone-binding
      mutations in MCM2, part of the replicative helicase, exacerbating histone PTM
      sister chromatid asymmetry. This work reveals how histones are inherited to
      sister chromatids and identifies a mechanism by which the replication machinery
      ensures symmetric cell division.

PMID- 30115745
TI  - A mechanism for preventing asymmetric histone segregation onto replicating DNA
      strands.
AB  - How parental histone (H3-H4)2 tetramers, the primary carriers of epigenetic
      modifications, are transferred onto leading and lagging strands of DNA
      replication forks for epigenetic inheritance remains elusive. Here we show that
      parental (H3-H4)2 tetramers are assembled into nucleosomes onto both leading and
      lagging strands, with a slight preference for lagging strands. The lagging-strand
      preference increases markedly in budding yeast cells lacking Dpb3 and Dpb4, two
      subunits of the leading strand DNA polymerase, Pol epsilon, owing to the
      impairment of parental (H3-H4)2 transfer to leading strands. Dpb3-Dpb4 binds H3
      H4 in vitro and participates in the inheritance of heterochromatin. These results
      indicate that different proteins facilitate the transfer of parental (H3-H4)2
      onto leading versus lagging strands and that Dbp3-Dpb4 plays an important role in
      this poorly understood process.

PMID- 30115747
TI  - The cloak, dagger, and shield: proteases in plant-pathogen interactions.
AB  - Plants sense the presence of pathogens or pests through the recognition of
      evolutionarily conserved microbe- or herbivore-associated molecular patterns or
      specific pathogen effectors, as well as plant endogenous danger-associated
      molecular patterns. This sensory capacity is largely mediated through plasma
      membrane and cytosol-localized receptors which trigger complex downstream immune
      signaling cascades. As immune signaling outputs are often associated with a high
      fitness cost, precise regulation of this signaling is critical. Protease-mediated
      proteolysis represents an important form of pathway regulation in this context.
      Proteases have been widely implicated in plant-pathogen interactions, and their
      biochemical mechanisms and targets continue to be elucidated. During the plant
      and pathogen arms race, specific proteases are employed from both the plant and
      the pathogen sides to contribute to either defend or invade. Several pathogen
      effectors have been identified as proteases or protease inhibitors which act to
      functionally defend or camouflage the pathogens from plant proteases and immune
      receptors. In this review, we discuss known protease functions and protease
      regulated signaling processes involved in both sides of plant-pathogen
      interactions.

PMID- 30115748
TI  - Glycans and glycosaminoglycans in neurobiology: key regulators of neuronal cell
      function and fate.
AB  - The aim of the present study was to examine the roles of l-fucose and the
      glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin sulfate/dermatan
      sulfate (CS/DS) with selected functional molecules in neural tissues. Cell
      surface glycans and GAGs have evolved over millions of years to become cellular
      mediators which regulate fundamental aspects of cellular survival. The
      glycocalyx, which surrounds all cells, actuates responses to growth factors,
      cytokines and morphogens at the cellular boundary, silencing or activating
      downstream signaling pathways and gene expression. In this review, we have
      focused on interactions mediated by l-fucose, KS and CS/DS in the central and
      peripheral nervous systems. Fucose makes critical contributions in the area of
      molecular recognition and information transfer in the blood group substances,
      cytotoxic immunoglobulins, cell fate-mediated Notch-1 interactions, regulation of
      selectin-mediated neutrophil extravasation in innate immunity and CD-34-mediated
      new blood vessel development, and the targeting of neuroprogenitor cells to
      damaged neural tissue. Fucosylated glycoproteins regulate delivery of synaptic
      neurotransmitters and neural function. Neural KS proteoglycans (PGs) were
      examined in terms of cellular regulation and their interactive properties with
      neuroregulatory molecules. The paradoxical properties of CS/DS isomers decorating
      matrix and transmembrane PGs and the positive and negative regulatory cues they
      provide to neurons are also discussed.

PMID- 30115749
TI  - Studying the differential efficacy of postsymptom antitoxin treatment in type A
      versus type B botulism using a rabbit spirometry model.
AB  - Botulinum neurotoxin (BoNT) serotypes A, B and E are responsible for most cases
      of human botulism. The only approved therapy for botulism is antitoxin treatment
      administered to patients after symptom onset. However, a recent meta-analysis of
      antitoxin efficacy in human botulism cases over the past century concluded that a
      statistically significant reduction in mortality is associated with the use of
      type E and type A antitoxin, but not with type B antitoxin. Animal models could
      be highly valuable in studying postsymptom antitoxin efficacy (PSAE). However,
      the few attempts to evaluate PSAE in animals relied on subjective observations
      and showed ~50% protection. Recently, we developed a novel spirometry model for
      the quantitative evaluation of PSAE in rabbits and used it to demonstrate full
      protection against BoNT/E. In the current study, a comparative evaluation of PSAE
      in botulism types A and B was conducted using this quantitative respiratory
      model. A lethal dose of each toxin induced a comparable course of disease both in
      terms of time to symptoms (TTS, 41.9+/-1.3 and 40.6+/-1.1 h, respectively) and of
      time to death (TTD, 71.3+/-3.1 and 66.3+/-1.7 h, respectively). However, in
      accordance with the differential serotypic PSAE observed in humans, postsymptom
      antitoxin treatment was fully effective only in BoNT/A-intoxicated rabbits. This
      serotypic divergence was reflected by a positive and statistically significant
      correlation between TTS and TTD in BoNT/A-intoxicated rabbits (r=0.91, P=0.0006),
      but not in those intoxicated with BoNT/B (r=0.06, P=0.88). The rabbit spirometry
      system might be useful in the evaluation toolkit of botulism therapeutics,
      including those under development and intended to act when antitoxin is no longer
      effective.

PMID- 30115752
TI  - Cell scientist to watch - Pere Roca-Cusachs.
AB  - Pere Roca-Cusachs received his doctorate in cellular biophysics from the
      University of Barcelona, Spain, in 2007, having worked with Daniel Navajas on
      mechanical properties of cells using atomic force microscopy. He then joined the
      laboratory of Michael Sheetz at Columbia University, USA, to study integrin
      mediated mechanotransduction. In 2012, Pere established his own research group
      with a joint position between the Institute for Bioengineering of Catalonia
      (IBEC) and the University of Barcelona. His research focuses on the mechanisms
      cells employ to detect and respond to mechanical signals. Pere is the recipient
      of an EMBO young investigator award and has received numerous national awards.

PMID- 30115753
TI  - First person - Rini Ravindran.
AB  - First Person is a series of interviews with the first authors of a selection of
      papers published in Journal of Cell Science, helping early-career researchers
      promote themselves alongside their papers. Rini Ravindran is the first author on
      'New ubiquitin-dependent mechanisms regulating the Aurora B-protein phosphatase 1
      balance in Saccharomyces cerevisiae', published in Journal of Cell Science. Rini
      is a PhD student in the lab of Kelly Tatchell at LSU Health Sciences Center in
      Shreveport, Louisiana, USA, investigating the maturation and regulation of
      protein phosphatase 1 (PP1).

PMID- 30115751
TI  - The kinetochore-microtubule interface at a glance.
AB  - Accurate chromosome segregation critically depends on the formation of
      attachments between microtubule polymers and each sister chromatid. The
      kinetochore is the macromolecular complex that assembles at the centromere of
      each chromosome during mitosis and serves as the link between the DNA and the
      microtubules. In this Cell Science at a Glance article and accompanying poster,
      we discuss the activities and molecular players that are involved in generating
      kinetochore-microtubule attachments, including the initial stages of lateral
      kinetochore-microtubule interactions and maturation to stabilized end-on
      attachments. We additionally explore the features that contribute to the ability
      of the kinetochore to track with dynamic microtubules. Finally, we examine the
      contributions of microtubule-associated proteins to the organization and
      stabilization of the mitotic spindle and the control of microtubule dynamics.

PMID- 30115750
TI  - Correction of cognitive deficits in mouse models of Down syndrome by a
      pharmacological inhibitor of DYRK1A.
AB  - Growing evidence supports the implication of DYRK1A in the development of
      cognitive deficits seen in Down syndrome (DS) and Alzheimer's disease (AD). We
      here demonstrate that pharmacological inhibition of brain DYRK1A is able to
      correct recognition memory deficits in three DS mouse models with increasing
      genetic complexity [Tg(Dyrk1a), Ts65Dn, Dp1Yey], all expressing an extra copy of
      Dyrk1a Overexpressed DYRK1A accumulates in the cytoplasm and at the synapse.
      Treatment of the three DS models with the pharmacological DYRK1A inhibitor
      leucettine L41 leads to normalization of DYRK1A activity and corrects the novel
      object cognitive impairment observed in these models. Brain functional magnetic
      resonance imaging reveals that this cognitive improvement is paralleled by
      functional connectivity remodelling of core brain areas involved in
      learning/memory processes. The impact of Dyrk1a trisomy and L41 treatment on
      brain phosphoproteins was investigated by a quantitative phosphoproteomics
      method, revealing the implication of synaptic (synapsin 1) and cytoskeletal
      components involved in synaptic response and axonal organization. These results
      encourage the development of DYRK1A inhibitors as drug candidates to treat
      cognitive deficits associated with DS and AD.

PMID- 30115754
TI  - Phosphatidylcholine synthesis regulates triglyceride storage and chylomicron
      secretion by Caco2 cells.
AB  - Intracellular lipid droplets (LDs) supply fatty acids for energy, membrane
      biogenesis, and lipoprotein secretion. The surface monolayer of LDs is composed
      of phospholipids, primarily phosphatidylcholine (PC), that stabilize the neutral
      lipid core of triglyceride (TG). To determine the relationship between PC
      synthesis and TG storage and secretion in chylomicrons, we used a model of
      intestinal-derived human epithelial colorectal adenocarcinoma (Caco2) cells with
      knockout of PCYT1A, which encodes the rate-limiting enzyme CTP:phosphocholine
      cytidylyltransferase (CCT)alpha in the CDP-choline pathway, that were treated
      with the fatty acid oleate. CRISPR/Cas9 knockout of CCTalpha in Caco2 cells
      (Caco2-KO cells) reduced PC synthesis by 50%. Compared with Caco2 cells, Caco2-KO
      cells exposed to oleate had fewer and larger LDs and greater TG accumulation as a
      result. The addition of exogenous lysophosphatidylcholine to Caco2-KO cells
      reversed the LD morphology defect. Caco2-KO cells, differentiated into epithelial
      monolayers, accumulated intracellular TG and had deficient TG and chylomicron
      associated apoB48 secretion; apoB100 secretion was unaffected by CCTalpha
      knockout or oleate. Metabolic-labeling and LD imaging of Caco2-KO cells indicated
      preferential shuttling of de novo synthesized TG into larger LDs rather than into
      chylomicrons. Thus, reduced de novo PC synthesis in Caco2 cells enhances TG
      storage in large LDs and inhibits apoB48 chylomicron secretion.

PMID- 30115755
TI  - MS-based lipidomics of human blood plasma: a community-initiated position paper
      to develop accepted guidelines.
AB  - Human blood is a self-regenerating lipid-rich biological fluid that is routinely
      collected in hospital settings. The inventory of lipid molecules found in blood
      plasma (plasma lipidome) offers insights into individual metabolism and
      physiology in health and disease. Disturbances in the plasma lipidome also occur
      in conditions that are not directly linked to lipid metabolism; therefore, plasma
      lipidomics based on MS is an emerging tool in an array of clinical diagnostics
      and disease management. However, challenges exist in the translation of such
      lipidomic data to clinical applications. These relate to the reproducibility,
      accuracy, and precision of lipid quantitation, study design, sample handling, and
      data sharing. This position paper emerged from a workshop that initiated a
      community-led process to elaborate and define a set of generally accepted
      guidelines for quantitative MS-based lipidomics of blood plasma or serum, with
      harmonization of data acquired on different instrumentation platforms across
      independent laboratories as an ultimate goal. We hope that other fields may
      benefit from and follow such a precedent.

PMID- 30115758
TI  - Novel lncRNA LINC00844 Regulates Prostate Cancer Cell Migration and Invasion
      through AR Signaling.
AB  - : The human genome is mostly transcribed, yielding a rich repository of noncoding
      transcripts that are involved in a myriad of biological processes including
      cancer. However, how many noncoding transcripts such as long noncoding RNAs
      (lncRNA) function in cancer is still unclear. This study identified a novel set
      of clinically relevant androgen-regulated lncRNAs in prostate cancer. Among this
      group, LINC00844 was demonstrated to be a direct androgen-regulated target that
      is actively transcribed in androgen receptor (AR)-dependent prostate cancer
      cells. The expression of LINC00844 is higher in normal prostate compared with
      malignant and metastatic prostate cancer clinical specimens, and patients with
      low expression had a poor prognosis and significantly increased biochemical
      recurrence, suggesting LINC00844 functions in suppressing tumor progression and
      metastasis. Indeed, in vitro loss-of-function studies revealed that LINC00844
      prevents prostate cancer cell migration and invasion. Moreover, findings from
      gene expression profiling analysis indicated that LINC00844 functions in trans,
      affecting global androgen-regulated gene transcription. Mechanistic evidence
      reveals that LINC00844 is important in facilitating AR binding to the chromatin.
      Finally, LINC00844 mediates its phenotypic effects in part by activating the
      expression of NDRG1, a crucial cancer metastasis suppressor. Collectively,
      LINC00844 is a novel coregulator of AR that plays a central role in the androgen
      transcriptional network and the development and progression of prostate cancer.
      IMPLICATIONS: This study highlights the function of the lncRNA, LINC00844, in
      regulating global AR-regulated genes in prostate cancer by modulating AR binding
      to chromatin.

PMID- 30115756
TI  - Tyrosine 450 in the Voltage- and Calcium-Gated Potassium Channel of Large
      Conductance Channel Pore-Forming (slo1) Subunit Mediates Cholesterol Protection
      against Alcohol-Induced Constriction of Cerebral Arteries.
AB  - Alcohol (ethanol) at physiologically relevant concentrations (<100 mM) constricts
      cerebral arteries via inhibition of voltage- and calcium-gated potassium channels
      of large conductance (BK) located in vascular smooth muscle (VSM). These channels
      consist of channel-forming slo1 (cbv1, KCNMA1) and accessory beta1 (KCNMB1)
      subunits. An increase in VSM cholesterol (CLR) via either dietary CLR intake or
      in vitro CLR enrichment was shown to protect against endothelium-independent,
      alcohol-induced constriction of cerebral arteries. The molecular mechanism(s) of
      this protection remains unknown. Here, we demonstrate that CLR enrichment of de
      endothelialized middle cerebral arteries (MCAs) of rat increased CLR content in
      the VSM in a concentration-dependent manner. CLR enrichment blunted MCA
      constriction evoked by 18-75 mM but not by 100 mM alcohol. MCA enrichment with
      coprostanol (COPR) also blunted vasoconstriction by 50 mM alcohol, despite the
      fact that COPR and CLR differ in their ability to modify several major physical
      properties of the bilayer. CLR protection against 50 but not 100 mM alcohol was
      also observed in C57BL/6 and KCNMB1 knockout (KO) mice. Permeabilization of
      KCNMA1 KO MCAs with Y450Fcbv1 totally ablated CLR, but not COPR protection
      against vasoconstriction by 50 mM alcohol. Thus, CLR and alcohol interact at the
      level of the BK channel slo1 subunit, with Y450 being critical for CLR protection
      against alcohol-induced vasoconstriction. We document for the first time a
      functional competition between CLR and alcohol in regulating cerebral artery
      diameter and a critical role of a single amino acid within the BK channel pore
      forming subunit in controlling CLR-alcohol interaction at the organ level.

PMID- 30115757
TI  - Midazolam-Resistant Seizures and Brain Injury after Acute Intoxication of
      Diisopropylfluorophosphate, an Organophosphate Pesticide and Surrogate for Nerve
      Agents.
AB  - Organophosphates (OP) such as the pesticide diisopropylfluorophosphate (DFP) and
      the nerve agent sarin are lethal chemicals that induce seizures, status
      epilepticus (SE), and brain damage. Midazolam, a benzodiazepine modulator of
      synaptic GABA-A receptors, is currently considered as a new anticonvulsant for
      nerve agents. Here, we characterized the time course of protective efficacy of
      midazolam (0.2-5 mg/kg, i.m.) in rats exposed to DFP, a chemical threat agent and
      surrogate for nerve agents. Behavioral and electroencephalogram (EEG) seizures
      were monitored for 24 hours after DFP exposure. The extent of brain injury was
      determined 3 days after DFP exposure by unbiased stereologic analyses of valid
      markers of neurodegeneration and neuroinflammation. Seizures were elicited within
      ~8 minutes after DFP exposure that progressively developed into persistent SE
      lasting for hours. DFP exposure resulted in massive neuronal injury or necrosis,
      neurodegeneration of principal cells and interneurons, and neuroinflammation as
      evident by extensive activation of microglia and astrocytes in the hippocampus,
      amygdala, and other brain regions. Midazolam controlled seizures,
      neurodegeneration, and neuroinflammation when given early (10 minutes) after DFP
      exposure, but it was less effective when given at 40 minutes or later. Delayed
      therapy (>=40 minutes), a simulation of the practical therapeutic window for
      first responders or hospital admission, was associated with reduced seizure
      protection and neuroprotection. These results strongly reaffirm that the DFP
      induced seizures and brain damage are progressively resistant to delayed
      treatment with midazolam, confirming the benzodiazepine refractory SE after OP
      intoxication. Thus, novel anticonvulsants superior to midazolam or adjunct
      therapies that enhance its efficacy are needed for effective treatment of
      refractory SE.

PMID- 30115759
TI  - Impeding Circulating Tumor Cell Reseeding Decelerates Metastatic Progression and
      Potentiates Chemotherapy.
AB  - : Circulating tumor cells (CTCs) are commonly detected in the systemic blood of
      patients with cancer with metastatic tumors. However, the mechanisms controlling
      the viability of cancer cells in blood and length of time spent in circulation,
      as well as their potential for generating additional tumors are still undefined.
      Here, it is demonstrated that CX3CR1, a chemokine receptor, drives reseeding of
      breast CTCs to multiple organs. Antagonizing this receptor dramatically impairs
      the progression of breast cancer cells in a relevant model of human metastatic
      disease, by affecting both tumor growth and numerical expansion. Notably,
      therapeutic targeting of CX3CR1 prolongs CTC permanence in the blood, both
      promoting their spontaneous demise by apoptosis and counteracting metastatic
      reseeding. These effects lead to containment of metastatic progression and
      extended survival. Finally, targeting CX3CR1 improves blood exposure of CTCs to
      doxorubicin and in combination with docetaxel shows synergistic effects in
      containing overall tumor burden. IMPLICATIONS: The current findings shed light on
      CTCs reseeding dynamics and support the development of CX3CR1 antagonism as a
      viable strategy to counteract metastatic progression.

PMID- 30115760
TI  - The role of nonmuscle myosin II in polydrug memories and memory reconsolidation.
AB  - Using pharmacologic and genetic approaches targeting actin or the actin-driving
      molecular motor, nonmuscle myosin II (NMII), we previously discovered an
      immediate, retrieval-independent, and long-lasting disruption of methamphetamine-
      (METH-) and amphetamine-associated memories. A single intrabasolateral amygdala
      complex infusion or systemic administration of the NMII inhibitor Blebbistatin
      (Blebb) is sufficient to produce this disruption, which is selective, having no
      retrieval-independent effect on memories for fear, food reward, cocaine, or
      morphine. However, it was unclear if Blebb treatment would disrupt memories of
      other stimulants and amphetamine class drugs, such as nicotine (NIC) or
      mephedrone (MEPH; bath salts). Moreover, many individuals abuse multiple drugs,
      but it was unknown if Blebb could disrupt polydrug memories, or if the inclusion
      of another substance would render Blebb no longer able to disrupt METH-associated
      memories. Therefore, the present study had two primary goals: (1) to determine
      the ability of Blebb to disrupt NIC- or MEPH-associated memories, and (2) to
      determine the ability of METH to modify other unconditioned stimulus (US)
      associations' susceptibility to Blebb. To this end, using the conditional place
      preference model, mice were conditioned to NIC and MEPH alone or METH in
      combination with NIC, morphine, or foot shock. We report that, unlike METH, there
      was no retrieval-independent effect of Blebb on NIC- or MEPH-associated memories.
      However, similar to cocaine, reconsolidation of the memory for both drugs was
      disrupted. Further, when combined with METH administration, NIC- and morphine-,
      but not fear-, associated memories were rendered susceptible to disruption by
      Blebb. Given the high rate of polydrug use and the resurgence of METH use, these
      results have important implications for the treatment of substance use disorder.

PMID- 30115761
TI  - Repeated cocaine exposure dysregulates cognitive control over cue-evoked reward
      seeking behavior during Pavlovian-to-instrumental transfer.
AB  - Drug-paired cues acquire powerful motivational properties, but only lead to
      active drug-seeking behavior if they are potent enough to overwhelm the cognitive
      control processes that serve to suppress such urges. Studies using the Pavlovian
      to-instrumental transfer (PIT) task have shown that rats pretreated with cocaine
      or amphetamine exhibit heightened levels of cue-motivated food-seeking behavior,
      suggesting that exposure to these drugs sensitizes the incentive motivational
      system. However, the PIT testing protocol can also create conflict between two
      competing behavioral responses to the reward-paired cue: active reward seeking
      (e.g., lever pressing) and passive conditioned food-cup approach behavior. We
      therefore investigated whether repeated cocaine exposure alters the way in which
      rats use cue-based reward expectations to resolve such conflict. In-depth
      analysis of previously published and new research confirmed that when drug-naive
      rats are given a cue that signals the timing of a delayed noncontingent reward,
      they adaptively transition from reward seeking to conditioned approach behavior,
      facilitating efficient collection of the predicted reward. In contrast, cocaine
      exposed rats exhibit pronounced behavioral dysregulation, increasing, rather than
      suppressing, their reward-seeking behavior over time, disrupting their ability to
      passively collect reward. Such findings speak to the important and sometimes
      overlooked role that cognitive control plays in determining the motivational
      impact of cues associated with drug and nondrug rewards.

PMID- 30115762
TI  - Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced
      memory deficits and reduces relapse.
AB  - Prolonged use of methamphetamine (meth) has been associated with episodic memory
      deficits in humans, and preclinical rat models of meth self-administration
      indicate the memory deficits are a consequence of meth use. Others have suggested
      that the meth-induced memory deficits may promote a cyclical pattern of drug use,
      abstinence, and relapse, although preclinical evidence for this relationship is
      somewhat lacking. The memory deficits in preclinical models manifest as a loss of
      novel object recognition (NOR) memory. These deficits occur one to two weeks
      after cessation of meth use and involve the perirhinal cortex, a parahippocampal
      region essential to NOR memory. We hypothesized that a loss of perirhinal cortex
      function contributes to both the NOR memory deficits and increased vulnerability
      to relapse in a novel-cue reinstatement model. To test this, we attempted to
      restore NOR memory in meth rats using an excitatory Gq-DREADD in perirhinal
      neurons. Activation of these neurons not only reversed the meth-induced deficit
      in NOR memory, but also restored novelty salience in a novel-cue reinstatement
      model. Thus, perirhinal cortex functionality contributes to both memory deficits
      in relapse in a long-access model of meth self-administration in rats, and
      chemogenetic restoration of perirhinal function restores memory and reduces
      relapse.

PMID- 30115763
TI  - Heterogeneous dopamine signals support distinct features of motivated actions:
      implications for learning and addiction.
AB  - Despite decades of research, investigations into effective neural and
      pharmacological therapies for many drugs of abuse, such as cocaine, have produced
      no FDA-approved approaches. This difficulty derives from the complexity of
      substance use disorders, which encompass a variety of behavioral, psychological,
      and neural circuit-based changes that occur as a result of repeated experience
      with the drug. Dopamine signaling has been demonstrated to play a key role in
      several aspects of drug abuse-from mediating its reinforcing properties and drug
      seeking to triggering relapse-while also mediating a number of important aspects
      of normal (nondrug related) motivated behaviors and actions. Real-time recording
      methods such as in vivo voltammetry, electrophysiology, and calcium imaging
      demonstrate that the signaling properties of dopamine for motivationally relevant
      stimuli are highly dynamic and spatiotemporally circumscribed within afferent
      target regions. In this review, we identify the origins and functional
      consequences of heterogeneous dopamine release in the limbic system, and how
      these properties are persistently altered in the drug-experienced brain. We
      propose that these spatiotemporally parallel dopaminergic signals are
      simultaneously available to the animal, but that these circuits are impaired
      following prolonged drug experience by disrupting the location and content of
      dopamine signals in afferent target regions. These findings are discussed in the
      context of relapse and pathways to discovering new treatments for addiction
      disorders.

PMID- 30115764
TI  - Synaptic plasticity mechanisms common to learning and alcohol use disorder.
AB  - Alcohol use disorders include drinking problems that span a range from binge
      drinking to alcohol abuse and dependence. Plastic changes in synaptic efficacy,
      such as long-term depression and long-term potentiation are widely recognized as
      mechanisms involved in learning and memory, responses to drugs of abuse, and
      addiction. In this review, we focus on the effects of chronic ethanol (EtOH)
      exposure on the induction of synaptic plasticity in different brain regions. We
      also review findings indicating that synaptic plasticity occurs in vivo during
      EtOH exposure, with a focus on ex vivo electrophysiological indices of
      plasticity. Evidence for effects of EtOH-induced or altered synaptic plasticity
      on learning and memory and EtOH-related behaviors is also reviewed. As this
      review indicates, there is much work needed to provide more information about the
      molecular, cellular, circuit, and behavioral consequences of EtOH interactions
      with synaptic plasticity mechanisms.

PMID- 30115766
TI  - Highway to hell or magic smoke? The dose-dependence of Delta9-THC in place
      conditioning paradigms.
AB  - The prerequisites for responsible cannabis use are at the heart of current
      inquiries into cannabis decriminalization by policy makers as well as academic
      and nonacademic stakeholders at a global scale. Delta9-tetrahydrocannabinol
      (Delta9-THC), the prime psychoactive compound of the cannabis sativa, as well as
      cannabimimetics that resemble the pharmacological properties and psychological
      effects of Delta9-THC, lend themselves handsomely to the preclinical scrutiny of
      reward-related behavior because they carry marked translational value. Although a
      functional dichotomy of the psychological effects of Delta9-THC (rewarding versus
      aversive) has been abundantly reported in place conditioning (PC) paradigms, and
      might be best attributed to a dose-dependence of Delta9-THC, most PC studies with
      Delta9-THC feature no significant effects at all. Therefore, after decades of
      rigorous research, it still remains undetermined whether Delta9-THC generally
      exerts rewarding or aversive effects in rodents. Here, we set out to extrapolate
      the commonly alleged dose-dependence of the rewarding and aversive effects of
      Delta9-THC from the existing literature, at the behavioral pharmacological level
      of analysis. Specifically, our meta-analysis investigated: (i) the alleged
      bidirectional effects and dose-dependence of Delta9-THC in the PC test; (ii)
      methodological inconsistencies between PC studies; and (iii) other
      pharmacological studies on cannabinoids (i.e., dopamine release, anxiety, stress,
      conditioned taste aversion, catalepsy) to substantiate the validity of PC
      findings. Our findings suggest that: (i) Delta9-THC dose-dependently generates
      rewarding (1 mg/kg) and aversive (5 mg/kg) effects in PC; (ii) an inconsistent
      use of priming injections hampers a clear establishment of the rewarding effects
      of Delta9-THC in PC tests and might explain the seemingly contradictory plethora
      of nonsignificant THC studies in the PC test; and (iii) other pharmacological
      studies on Delta9-THC substantiate the dose-dependent biphasic effects of Delta9
      THC in PC. A standardized experimental design would advance evidence-based
      practice in future PC studies with Delta9-THC and facilitate the pointed
      establishment of rewarding and aversive effects of the substance.

PMID- 30115767
TI  - Chasing the addicted engram: identifying functional alterations in Fos-expressing
      neuronal ensembles that mediate drug-related learned behavior.
AB  - Given that addiction has been characterized as a disorder of maladaptive learning
      and memory, one critical question is whether there are unique physical
      adaptations within neuronal ensembles that support addiction-related learned
      behavior. The search for the physical mechanisms of encoding these and other
      memories in the brain, often called the engram as a whole, continues despite
      decades of research. As we develop new technologies and tools that allow us to
      study cue- and behavior-activated Fos-expressing neuronal ensembles, the
      possibility of identifying the engrams of learning and memory is moving into the
      realm of reality rather than speculation. It has become clear from recent studies
      that there are specific functional, electrophysiological alterations unique to
      Fos-expressing ensemble neurons that may participate in encoding memories. The
      ultimate goal is to identify the addicted engram and reverse the physical changes
      that support this maladaptive form of learning.

PMID- 30115765
TI  - Cannabinoid disruption of learning mechanisms involved in reward processing.
AB  - The increasing use of cannabis, its derivatives, and synthetic cannabinoids for
      medicinal and recreational purposes has led to burgeoning interest in
      understanding the addictive potential of this class of molecules. It is estimated
      that ~10% of marijuana users will eventually show signs of dependence on the
      drug, and the diagnosis of cannabis use disorder (CUD) is increasing in the
      United States. The molecule that sustains the use of cannabis is Delta9
      tetrahydrocannabinol (Delta9-THC), and our knowledge of its effects, and those of
      other cannabinoids on brain function has expanded rapidly in the past two
      decades. Additionally, the identification of endogenous cannabinoid
      (endocannabinoid) systems in brain and their roles in physiology and behavior,
      demonstrate extensive involvement of these lipid signaling molecules in
      regulating CNS function. Here, we examine roles for endogenous cannabinoids in
      shaping synaptic activity in cortical and subcortical brain circuits, and we
      discuss mechanisms in which exogenous cannabinoids, such as Delta9-THC, interact
      with endocannabinoid systems to disrupt neuronal network oscillations. We then
      explore how perturbation of the interaction of this activity within brain reward
      circuits may lead to impaired learning. Finally, we propose that disruption of
      cellular plasticity mechanisms by exogenous cannabinoids in cortical and
      subcortical circuits may explain the difficulty in establishing viable
      cannabinoid self-administration models in animals.

PMID- 30115769
TI  - The hot 'n' cold of cue-induced drug relapse.
AB  - Environmental cues associated with rewards can acquire motivational properties.
      However, there is considerable variation in the extent to which a reward cue
      gains motivational control over behavior, depending on the individual and the
      form of the cue. When a discrete cue is paired with food reward, it acquires
      greater control over motivated behavior in some rats (sign-trackers, STs) than
      others (goal-trackers, GTs) as indicated by the propensity to approach the cue,
      the willingness to work to obtain it, and its ability to reinstate reward-seeking
      behavior. Here, we review studies that employ this ST/GT animal model to
      investigate characteristics of individuals that are especially susceptible to
      reward cue-elicited behavior and the involvement of dopamine and acetylcholine
      neuromodulator systems in the susceptibility to cue-induced drug relapse. First,
      we discuss individual differences in the attribution of incentive salience to
      different forms of reward cues and the involvement of the mesolimbic dopamine
      system. We then discuss individual differences in cognitive/attentional control
      and the contributions of the cholinergic system in processing reward cues. It is
      suggested that in STs a propensity to attribute motivational properties to a drug
      cue is combined with poor attentional control in the face of these cues, making
      them particularly vulnerable to transition from casual/experimental patterns of
      drug use to addiction and to cue-induced relapse.

PMID- 30115768
TI  - The impact of drugs of abuse on executive function: characterizing long-term
      changes in neural correlates following chronic drug exposure and withdrawal in
      rats.
AB  - Addiction has long been characterized by diminished executive function, control,
      and impulsivity management. In particular, these deficits often manifest
      themselves as impairments in reversal learning, delay discounting, and response
      inhibition. Understanding the neurobiological substrates of these behavioral
      deficits is of paramount importance to our understanding of addiction. Within the
      cycle of addiction, periods during and after withdrawal represent a particularly
      difficult point of intervention in that the negative physical symptoms associated
      with drug removal and drug craving increase the likelihood that the patient will
      relapse and return to drug use in order to abate these symptoms. Moreover, it is
      often during this time that drug induced deficits in executive function hinder
      the ability of the patient to refrain from drug use. Thus, it is necessary to
      understand the physiological and behavioral changes associated with withdrawal
      and drug craving-largely manifesting as deficits in executive control-to develop
      more effective treatment strategies. In this review, we address the long-term
      impact that drugs of abuse have on the behavioral and neural correlates that give
      rise to executive control as measured by reversal learning, delay discounting,
      and stop-signal tasks, focusing particularly on our work using rats as a model
      system.

PMID- 30115770
TI  - The long-term cognitive consequences of adolescent exposure to recreational drugs
      of abuse.
AB  - During adolescence, the brain continues to undergo vital developmental processes.
      In turn, complex behavioral and cognitive skills emerge. Unfortunately,
      neurobiological development during adolescence can be influenced by environmental
      factors such as drug exposure. Engaging in drug use during adolescence has been a
      long-standing health concern, especially how it predicts or relates to drug using
      behavior later in life. However, recent findings suggest that other behavioral
      domains, such as learning and memory, are also vulnerable to adolescent drug use.
      Moreover, it is becoming increasingly apparent that deficits in learning and
      memory following adolescent drug use endure into adulthood, well after drug
      exposure has subsided. Although persistent effects suggest an interaction between
      drug exposure and ongoing development during adolescence, the exact acute and
      long-term consequences of adolescent drug exposure on substrates of learning and
      memory are not fully understood. Thus, this review will summarize human and
      animal findings on the enduring cognitive deficits due to adolescent drug
      exposure. Moreover, due to the fact that adolescents are more likely to consume
      drugs of abuse legally available to adults, this review will focus on alcohol,
      nicotine, and marijuana. Further, given the critical role of the frontal cortex
      and hippocampus in various learning and memory domains, the impact adolescent use
      of the previous listed drugs on the neurobiology within these regions will also
      be discussed.

PMID- 30115773
TI  - Special issue covering the relationship between mechanisms of addiction and
      learning.

PMID- 30115771
TI  - Reconsolidation blockade for the treatment of addiction: challenges, new targets,
      and opportunities.
AB  - Addiction is a chronic, relapsing disorder. The progression to pathological drug
      seeking is thought to be driven by maladaptive learning processes which store and
      maintain associative memory, linking drug highs with cues and actions in the
      environment. These memories can encode Pavlovian associations which link
      predictive stimuli (e.g., people, places, and paraphernalia) with a hedonic drug
      high, as well as instrumental learning about the actions required to obtain drug
      associated incentives. Learned memories are not permanent however, and much
      recent interest has been generated in exploiting the process of reconsolidation
      to erase or significantly weaken maladaptive memories to treat several mental
      health disorders, including addictions. Normally reconsolidation serves to update
      and maintain the adaptive relevance of memories, however administration of
      amnestic agents within the critical "reconsolidation window" can weaken or even
      erase maladaptive memories. Here we discuss recent advances in the field,
      including ongoing efforts to translate preclinical reconsolidation research in
      animal models into clinical practice.

PMID- 30115774
TI  - Correction for Chung et al., "Downregulation of Poly(ADP-Ribose) Polymerase 1 by
      a Viral Processivity Factor Facilitates Lytic Replication of Gammaherpesvirus".

PMID- 30115775
TI  - Correction for Parolini et al., "Stability and Expression Levels of HLA-C on the
      Cell Membrane Modulate HIV-1 Infectivity".

PMID- 30115776
TI  - Man with severe abdominal pain.
AB  - CLINICAL INTRODUCTION: A 59-year-old man with no medical history presented to the
      ED with abdominal distension, vomiting and diffuse abdominal pain after drinking
      seven cups of white gourd drink (an authentic Asian drink composed mainly of
      white gourd). A chest radiograph was performed (figure
      1).emermed;35/9/571/F1F1F1Figure 1Chest radiograph. AP, anteroposterior.
      QUESTION: What is the most likely diagnosis?Crescent in doughnut sign,
      intussusceptionFalciform ligament sign, pneumoperitoneumStepladder sign, small
      bowel obstructionCoffee-bean sign, sigmoid colon volvulus.

PMID- 30115777
TI  - BET 1: Prehospital cardiac troponin testing to 'rule out' acute coronary
      syndromes using point of care assays.
AB  - A shortcut review of the literature was carried out to establish whether
      prehospital point of care (POC) troponin tests are reliable and accurate enough
      to detect acute coronary syndrome (ACS) in adult patients.Nine papers were found
      to be relevant to the clinical question following the below-described search
      strategies. The author, date and country of publication, patient group studied,
      study type, relevant outcomes, results and study weaknesses of those best papers
      are tabulated. It is concluded that based on the currently available evidence,
      POC troponin assays are insufficiently sensitive to 'rule out' ACS in the
      prehospital environment.

PMID- 30115779
TI  - BET 2: Twist score in cases of suspected paediatric testicular torsion.
AB  - A shortcut review of the literature was carried out to establish whether the
      Testicular Workup for Ischemia and Suspected Torsion (TWIST) score was reliable
      and accurate enough to rule out testicular torsion in the paediatric
      population.Four papers were found to be relevant to the clinical question
      following the below-described search strategies. The author, date and country of
      publication, patient group studied, study type, relevant outcomes, results and
      study weaknesses of those best papers are tabulated. It is concluded that based
      on the currently available evidence, a low-risk TWIST score has a high
      sensitivity and can be used in line with clinical judgement to rule out
      testicular torsion.

PMID- 30115772
TI  - Beyond simple tests of value: measuring addiction as a heterogeneous disease of
      computation-specific valuation processes.
AB  - Addiction is considered to be a neurobiological disorder of learning and memory
      because addiction is capable of producing lasting changes in the brain.
      Recovering addicts chronically struggle with making poor decisions that
      ultimately lead to relapse, suggesting a view of addiction also as a
      neurobiological disorder of decision-making information processing. How the brain
      makes decisions depends on how decision-making processes access information
      stored as memories in the brain. Advancements in circuit-dissection tools and
      recent theories in neuroeconomics suggest that neurally dissociable valuation
      processes access distinct memories differently, and thus are uniquely susceptible
      as the brain changes during addiction. If addiction is to be considered a
      neurobiological disorder of memory, and thus decision-making, the heterogeneity
      with which information is both stored and processed must be taken into account in
      addiction studies. Addiction etiology can vary widely from person to person. We
      propose that addiction is not a single disease, nor simply a disorder of learning
      and memory, but rather a collection of symptoms of heterogeneous neurobiological
      diseases of distinct circuit-computation-specific decision-making processes.

PMID- 30115780
TI  - Eighty-nine-year-old woman with abdominal pain and vomiting.
AB  - CLINICAL INTRODUCTION: An 89-year-old female patient presented to the ED with
      mild abdominal pain and a history of vomiting for 3 days. Because of dementia,
      further history was unclear. Vital signs were normal. Clinical examination
      revealed mild abdominal pain without defence or signs of peritonism. Bowel sounds
      were normal. Lab results showed a white cell count of 16x109/L, otherwise normal.
      There was no episode of vomiting during the ED consultation. A supine AXR was
      performed (figure 1).emermed;35/9/576/F1F1F1Figure 1Supine AXR. WHAT IS THE
      DIAGNOSIS?: Foreign bodyGallstone ileusColon obstructionIntestinal volvulus.

PMID- 30115781
TI  - Quantum-inspired computational imaging.
AB  - Computational imaging combines measurement and computational methods with the aim
      of forming images even when the measurement conditions are weak, few in number,
      or highly indirect. The recent surge in quantum-inspired imaging sensors,
      together with a new wave of algorithms allowing on-chip, scalable and robust data
      processing, has induced an increase of activity with notable results in the
      domain of low-light flux imaging and sensing. We provide an overview of the major
      challenges encountered in low-illumination (e.g., ultrafast) imaging and how
      these problems have recently been addressed for imaging applications in extreme
      conditions. These methods provide examples of the future imaging solutions to be
      developed, for which the best results are expected to arise from an efficient
      codesign of the sensors and data analysis tools.

PMID- 30115784
TI  - Don't lose race-conscious policies.

PMID- 30115785
TI  - News at a glance.

PMID- 30115786
TI  - New case of alleged bullying rocks the Max Planck Society.

PMID- 30115787
TI  - Critics pan EPA plan for weighing toxic chemical risks.

PMID- 30115782
TI  - The transcriptional landscape of polyploid wheat.
AB  - The coordinated expression of highly related homoeologous genes in polyploid
      species underlies the phenotypes of many of the world's major crops. Here we
      combine extensive gene expression datasets to produce a comprehensive, genome
      wide analysis of homoeolog expression patterns in hexaploid bread wheat. Bias in
      homoeolog expression varies between tissues, with ~30% of wheat homoeologs
      showing nonbalanced expression. We found expression asymmetries along wheat
      chromosomes, with homoeologs showing the largest inter-tissue, inter-cultivar,
      and coding sequence variation, most often located in high-recombination distal
      ends of chromosomes. These transcriptionally dynamic genes potentially represent
      the first steps toward neo- or subfunctionalization of wheat homoeologs.
      Coexpression networks reveal extensive coordination of homoeologs throughout
      development and, alongside a detailed expression atlas, provide a framework to
      target candidate genes underpinning agronomic traits in wheat.

PMID- 30115789
TI  - Study reignites debate about when Thera blew its top.

PMID- 30115788
TI  - AI takes on video games in quest for common sense.

PMID- 30115790
TI  - Detailed genome maps paths to better wheat.

PMID- 30115791
TI  - Tide of lies.

PMID- 30115792
TI  - Plant nutrient acquisition entices herbivore.

PMID- 30115793
TI  - Choosing the right input in cell signaling.

PMID- 30115794
TI  - Caged clusters shine brighter.

PMID- 30115795
TI  - Phase separation focuses DNA sensing.

PMID- 30115796
TI  - Photocatalytic upgrading of natural gas.

PMID- 30115797
TI  - Turning up translation in fragile X syndrome.

PMID- 30115798
TI  - Global warming policy: Is population left out in the cold?

PMID- 30115799
TI  - Harassment charges: Enough himpathy.

PMID- 30115800
TI  - Harassment charges: Journalists' role.

PMID- 30115801
TI  - Harassment charges: Injustice done?

PMID- 30115802
TI  - Harassment charges: Metoo but due process.

PMID- 30115803
TI  - Stereodivergent synthesis of 1,4-dicarbonyls by traceless charge-accelerated
      sulfonium rearrangement.
AB  - The chemistry of the carbonyl group is essential to modern organic synthesis. The
      preparation of substituted, enantioenriched 1,3- or 1,5-dicarbonyls is well
      developed, as their disconnection naturally follows from the intrinsic polarity
      of the carbonyl group. By contrast, a general enantioselective access to
      quaternary stereocenters in acyclic 1,4-dicarbonyl systems remains an unresolved
      problem, despite the tremendous importance of 2,3-substituted 1,4-dicarbonyl
      motifs in natural products and drug scaffolds. Here we present a broad
      enantioselective and stereodivergent strategy to access acyclic, polysubstituted
      1,4-dicarbonyls via acid-catalyzed [3,3]-sulfonium rearrangement starting from
      vinyl sulfoxides and ynamides. The stereochemistry at sulfur governs the absolute
      sense of chiral induction, whereas the double bond geometry dictates the relative
      configuration of the final products.

PMID- 30115804
TI  - Collective clog control: Optimizing traffic flow in confined biological and
      robophysical excavation.
AB  - Groups of interacting active particles, insects, or humans can form clusters that
      hinder the goals of the collective; therefore, development of robust strategies
      for control of such clogs is essential, particularly in confined environments.
      Our biological and robophysical excavation experiments, supported by
      computational and theoretical models, reveal that digging performance can be
      robustly optimized within the constraints of narrow tunnels by individual
      idleness and retreating. Tools from the study of dense particulate ensembles
      elucidate how idleness reduces the frequency of flow-stopping clogs and how
      selective retreating reduces cluster dissolution time for the rare clusters that
      still occur. Our results point to strategies by which dense active matter and
      swarms can become task capable without sophisticated sensing, planning, and
      global control of the collective.

PMID- 30115783
TI  - Shifting the limits in wheat research and breeding using a fully annotated
      reference genome.
AB  - An annotated reference sequence representing the hexaploid bread wheat genome in
      21 pseudomolecules has been analyzed to identify the distribution and genomic
      context of coding and noncoding elements across the A, B, and D subgenomes. With
      an estimated coverage of 94% of the genome and containing 107,891 high-confidence
      gene models, this assembly enabled the discovery of tissue- and developmental
      stage-related coexpression networks by providing a transcriptome atlas
      representing major stages of wheat development. Dynamics of complex gene families
      involved in environmental adaptation and end-use quality were revealed at
      subgenome resolution and contextualized to known agronomic single-gene or
      quantitative trait loci. This community resource establishes the foundation for
      accelerating wheat research and application through improved understanding of
      wheat biology and genomics-assisted breeding.

PMID- 30115805
TI  - Insulator-metal transition in dense fluid deuterium.
AB  - Dense fluid metallic hydrogen occupies the interiors of Jupiter, Saturn, and many
      extrasolar planets, where pressures reach millions of atmospheres. Planetary
      structure models must describe accurately the transition from the outer molecular
      envelopes to the interior metallic regions. We report optical measurements of
      dynamically compressed fluid deuterium to 600 gigapascals (GPa) that reveal an
      increasing refractive index, the onset of absorption of visible light near 150
      GPa, and a transition to metal-like reflectivity (exceeding 30%) near 200 GPa,
      all at temperatures below 2000 kelvin. Our measurements and analysis address
      existing discrepancies between static and dynamic experiments for the insulator
      metal transition in dense fluid hydrogen isotopes. They also provide new
      benchmarks for the theoretical calculations used to construct planetary models.

PMID- 30115806
TI  - 3D printed polyamide membranes for desalination.
AB  - Polyamide thickness and roughness have been identified as critical properties
      that affect thin-film composite membrane performance for reverse osmosis.
      Conventional formation methodologies lack the ability to control these properties
      independently with high resolution or precision. An additive approach is
      presented that uses electrospraying to deposit monomers directly onto a
      substrate, where they react to form polyamide. The small droplet size coupled
      with low monomer concentrations result in polyamide films that are smoother and
      thinner than conventional polyamides, while the additive nature of the approach
      allows for control of thickness and roughness. Polyamide films are formed with a
      thickness that is controllable down to 4-nanometer increments and a roughness as
      low as 2 nanometers while still exhibiting good permselectivity relative to a
      commercial benchmarking membrane.

PMID- 30115807
TI  - Origin of the bright photoluminescence of few-atom silver clusters confined in
      LTA zeolites.
AB  - Silver (Ag) clusters confined in matrices possess remarkable luminescence
      properties, but little is known about their structural and electronic properties.
      We characterized the bright green luminescence of Ag clusters confined in
      partially exchanged Ag-Linde Type A (LTA) zeolites by means of a combination of x
      ray excited optical luminescence-extended x-ray absorption fine structure, time
      dependent-density functional theory calculations, and time-resolved spectroscopy.
      A mixture of tetrahedral Ag4(H2O) x2+ (x = 2 and x = 4) clusters occupies the
      center of a fraction of the sodalite cages. Their optical properties originate
      from a confined two-electron superatom quantum system with hybridized Ag and
      water O orbitals delocalized over the cluster. Upon excitation, one electron of
      the s-type highest occupied molecular orbital is promoted to the p-type lowest
      unoccupied molecular orbitals and relaxes through enhanced intersystem crossing
      into long-lived triplet states.

PMID- 30115808
TI  - Plant iron acquisition strategy exploited by an insect herbivore.
AB  - Insect herbivores depend on their host plants to acquire macro- and
      micronutrients. Here we asked how a specialist herbivore and damaging maize pest,
      the western corn rootworm, finds and accesses plant-derived micronutrients. We
      show that the root-feeding larvae use complexes between iron and benzoxazinoid
      secondary metabolites to identify maize as a host, to forage within the maize
      root system, and to increase their growth. Maize plants use these same
      benzoxazinoids for protection against generalist herbivores and, as shown here,
      for iron uptake. We identify an iron transporter that allows the corn rootworm to
      benefit from complexes between iron and benzoxazinoids. Thus, foraging for an
      essential plant-derived complex between a micronutrient and a secondary
      metabolite shapes the interaction between maize and a specialist herbivore.

PMID- 30115809
TI  - Fragile X mental retardation 1 gene enhances the translation of large autism
      related proteins.
AB  - Mutations in the fragile X mental retardation 1 gene (FMR1) cause the most common
      inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA)
      translation, but identifying functional targets has been difficult. We analyzed
      quiescent Drosophila oocytes, which, like neural synapses, depend heavily on
      translating stored mRNA. Ribosome profiling revealed that FMR1 enhances rather
      than represses the translation of mRNAs that overlap previously identified FMR1
      targets, and acts preferentially on large proteins. Human homologs of at least 20
      targets are associated with dominant intellectual disability, and 30 others with
      recessive neurodevelopmental dysfunction. Stored oocytes lacking FMR1 usually
      generate embryos with severe neural defects, unlike stored wild-type oocytes,
      which suggests that translation of multiple large proteins by stored mRNAs is
      defective in fragile X syndrome and possibly other autism spectrum disorders.

PMID- 30115810
TI  - The universe in a classroom.

PMID- 30115813
TI  - Inverse relationship between serum hsCRP concentration and hand grip strength in
      older adults: a nationwide population-based study.
AB  - Despite the potential detrimental effects of systemic inflammation on muscle
      mass, which is mainly observed in patients with pathologic diseases, its role in
      muscle strength, especially in a healthy general population reflecting
      subclinical low-grade inflammation, is unclear. This is a nationally
      representative population-based, cross-sectional study from the Korea National
      Health and Nutrition Examination Survey, which enrolled 1,036 men aged >=50 years
      and 1,080 postmenopausal women. After adjustment for confounders, serum high
      sensitivity C-reactive protein (hsCRP) level was inversely associated with hand
      grip strength (HGS) in men. Consistently, compared with men in the lowest serum
      hsCRP quartile, those in the highest quartile showed a significant lower HGS,
      with a linear decrease of HGS across increasing serum hsCRP quartiles. Men with
      low muscle strength had 74.2% higher serum hsCRP than those without, and each
      standard deviation increment in serum hsCRP was associated with a multivariate
      adjusted odds ratio of 1.35 for the risk of low muscle strength in men. However,
      these associations were not statistically significant in women. These findings
      provide clinical evidence that chronic subclinical low-grade inflammation may
      contribute to the deterioration of muscle strength seen with aging, especially in
      men.

PMID- 30115812
TI  - Identification of IDH-mutant gliomas by a prognostic signature according to gene
      expression profiling.
AB  - BACKGROUND: Isocitrate dehydrogenase (IDH) mutations are the most common genetic
      aberrations in gliomagenesis. We aimed to build a high-efficiency prediction gene
      signature in patients with IDH-mutant glioma. METHODS: In total, 167 gliomas from
      Chinese Glioma Genome Atlas (CGGA) dataset were included for discovery. The
      Cancer Genome Atlas (TCGA) dataset was used for validation. R language was the
      main software environment for our statistical operation and graphics. RESULTS: We
      applied the Time-Dependent ROC Curve (timeROC) method to estimate the gene
      prediction accuracy of 3 years and 5 years in two datasets. Seven genes were
      selected for further analysis (AUC >= 0.7 in two datasets). A seven-gene
      enrichment score was established to predict the overall survival of 3 years and 5
      years for IDH- mutant glioma patients. Moreover, the seven-gene signature was an
      independent prognostic indicator for patients with IDH-mutant glioma. Gene
      Ontology (GO) Analysis of associated genes revealed signature-related biological
      process of cell cycle and division. CONCLUSION: We have identified a seven-gene
      signature that can provide a more accurate predictor of 3 years and 5 years for
      patients with IDH-mutant glioma. Moreover, the signature may potentially help
      neurosurgeons with the clinical personalized management of gliomas.

PMID- 30115815
TI  - Equivalent thicknesses of beam hardening filters consisting of aluminium, copper,
      Al/Cu and Al/Gold combinations and plumbiferous acrylic for 40 to 150 kVp
      diagnostic spectra.
AB  - PURPOSE: Beam hardening filters used to reduce patient doses typically consist of
      aluminium, copper, or a combination of both. Optically transparent filters
      containing lead in plumbiferous acrylic became available. One vendor also uses a
      combination of aluminium and gold. Data is provided to compare filter thicknesses
      in terms of half-value layer (HVL) for clinically relevant kVp. METHODS:
      Equivalent filter thicknesses were defined by identical kVp and 1st HVL.
      Equivalent copper filter thicknesses were calculated for aluminium and typical
      filters found in radiographic and interventional systems. A verified semi
      empirical spectrum calculation programme and National Institute of Standards and
      Technology (NIST) mass attenuation coefficients were applied. Lead acrylic
      filters were simulated by a two-component model of acrylic plus lead with mass
      thicknesses determined by matching 1 HVLs in Al at RQR5 using filter
      specifications. RESULTS: Coefficients are provided to convert mm Cu to mm Al and
      vice versa for tube potentials from 40 to 150 kVp. 1 mm Al corresponds to 27.8 +/
      1 MUm Cu over the entire energy range simulated. Using this simple model as
      opposed to simulations of all individual filters made from Al/Cu combinations (1
      and 2 mm Al, 1 Al + 0.1 and 0.2 Cu, 1.5 Al plus 0.3 and 0.6 Cu, 2 Al plus 0.1 Cu)
      for the entire energy range results in differences in equivalent Cu thicknesses
      below 4 MUm Cu (3 MUm for 50-150 kVp). kVp dependence is larger for filters
      containing larger Z elements. 1 mm Al plus 10 MUm gold used by Shimadzu
      corresponds to 75-80 MUm Cu, depending on kVp; plumbiferous acrylic with nominal
      filtrations of 1 Al plus 0.1 Cu, and 1 Al plus 0.2 Cu corresponded to 124-132
      MUm, and 206-232 MUm Cu, respectively. CONCLUSIONS: Experimental verification of
      the equivalence of aluminium and combined aluminium plus copper filters showed
      excellent agreement between calculated copper equivalent thickness and
      measurements with copper filters for clinical beams from 40 to 150 kVp.

PMID- 30115814
TI  - Lycopene ameliorates oxidative stress in the aging chicken ovary via activation
      of Nrf2/HO-1 pathway.
AB  - After 480 days of age, high-producing hens are likely to be subject to ovarian
      aging, mainly due to oxidative stress. In this study, the amelioration of ovarian
      aging in chickens, using a plant antioxidant, lycopene, was investigated. The
      activity of the Nrf2/HO-1 pathway in chicken ovaries at different ages (90, 150,
      280 and 580 days old) were compared to elucidate any age-related changes.
      Subsequently, the putative attenuating effect of lycopene (100 ng/mL) on ovarian
      aging was evaluated through the establishment of a D-gal-induced aging ovarian
      culture model. The cultured ovarian tissues of young (280 days) and old (580
      days) hens were treated with lycopene for 72 h to verify protective effects of
      lycopene on naturally aged ovaries. Results showed that the Nrf2/HO-1 pathway was
      down-regulated during the ovarian aging process. Lycopene rescued the decreased
      antioxidant capacity by increasing the activities of antioxidases and activating
      the Nrf2/HO-1 pathway in both D-gal-induced and naturally aged ovaries. Moreover,
      lycopene promoted cell proliferation and inhibited apoptosis in both D-gal
      induced and naturally aged ovaries. Lycopene also alleviated D-gal-induced
      mitochondrial damage in the living granulosa cells. In conclusion, lycopene can
      effectively ameliorate the oxidative stress in aging hen ovaries via the
      activation of the Nrf2/HO-1 pathway.

PMID- 30115816
TI  - Robust Channel Allocation with Heterogeneous Requirements for Wireless Mesh
      Backbone Networks.
AB  - When multiple mobile sensors and actuators share a common wireless mesh backbone
      network of defence systems, the channel allocation mechanism must guarantee the
      heterogeneous link requirements under conditions of uncertainty. In this paper, a
      robust channel allocation mechanism is proposed by exploiting partially
      overlapped channels for directional multi-channel wireless mesh networks. The
      approach relies on a chance-constrained optimization problem, in which the
      objective is to minimize the spectrum usage of the network, and the constraints
      are the signal-to-interference-plus-noise ratio requirements of links with
      uncertainty. We convert the proposed integer non-linear optimization problem into
      a mixed-integer convex problem by using efficient transition and approximation.
      The optimal channel allocation is obtained by solving the proposed optimization
      problem which adapts to the heterogeneous link and robustness requirements. The
      simulation results show that the proposed method ensures the heterogeneous link
      requirements under uncertain conditions while minimizing the spectrum usage of
      the network.

PMID- 30115817
TI  - Core Symptoms of Major Depressive Disorder among Palliative Care Patients.
AB  - A valid method to diagnose depression in palliative care has not been
      established. In this study, we aim to determine the prevalence of depression and
      the discriminant validity of the items of four sets of diagnostic criteria in
      palliative care. This is a cross-sectional study on 240 palliative care patients
      where the presence of depression was based on the Diagnostic and Statistical
      Manual of Mental Disorders, DSM-IV Criteria, Modified DSM-IV Criteria, Cavanaugh
      Criteria, and Endicott's Criteria's. Anxiety, depression, and distress were
      measured with Hospital Anxiety and Depression Scale and Distress Thermometer. The
      prevalence of depression among the palliative care patients was highest based on
      the Modified DSM-IV Criteria (23.3%), followed by the Endicott's Criteria
      (13.8%), DSM-IV Criteria (9.2%), and Cavanaugh Criteria (5%). There were
      significant differences (p < 0.05) in the depressive symptoms showed by DSM-IV
      item 1 (dysphoric mood), item 2 (loss of interest or pleasure), and Endicott's
      criteria item 8 (brooding, self-pity, or pessimism) among the palliative
      patients, even after adjustment for the anxiety symptoms and distress level. We
      found that dysphoric mood, loss of interest, and pessimism are the main features
      of depression in palliative patients. These symptoms should be given more
      attention in identifying depression in palliative care patients.

PMID- 30115818
TI  - Migration and Fate of Acid Mine Drainage Pollutants in Calcareous Soil.
AB  - As a major province of mineral resources in China, Shanxi currently has 6000
      mines of various types, and acid mine drainage (AMD) is a major pollutant from
      the mining industry. Calcareous soil is dominant in western North China
      (including the Shanxi Province), therefore, clarifying the migration behavior of
      the main AMD pollutants (H+, S, Fe, heavy metals) in calcareous soil is essential
      for remediating AMD-contaminated soil in North China. In this study, the
      migration behavior of the main pollutants from AMD in calcareous soil was
      investigated using soil columns containing 20 cm of surficial soil to which
      different volumes of simulated AMD were added in 20 applications. Filtrate that
      was discharged from the soil columns and the soil samples from the columns were
      analyzed. Almost all of the Fe ions (>99%) from the AMD were intercepted in the 0
      20 cm depth of the soil. Although >80% of SO42- was retained, the retention
      efficiency of the soil for SO42- was lower than it was for Fe. Cu, as a
      representative of heavy metals that are contained in AMD, was nearly totally
      retained by the calcareous soil. However, Cu had a tendency to migrate downward
      with the gradual acidification of the upper soil. In addition, CaCO3 was
      transformed into CaSO4 in AMD-contaminated soil. The outcomes of this study are
      valuable for understanding the pollution of calcareous soil by AMD and can
      provide key parameters for remediating AMD-contaminated soil.

PMID- 30115811
TI  - Remote ischemic conditioning: a promising therapeutic intervention for multi
      organ protection.
AB  - Despite decades of formidable exploration, multi-organ ischemia-reperfusion
      injury (IRI) encountered, particularly amongst elderly patients with clinical
      scenarios, such as age-related arteriosclerotic vascular disease, heart surgery
      and organ transplantation, is still an unsettled conundrum that besets
      clinicians. Remote ischemic conditioning (RIC), delivered via transient,
      repetitive noninvasive IR interventions to distant organs or tissues, is regarded
      as an innovative approach against IRI. Based on the available evidence, RIC holds
      the potential of affording protection to multiple organs or tissues, which
      include not only the heart and brain, but also others that are likely susceptible
      to IRI, such as the kidney, lung, liver and skin. Neuronal and humoral signaling
      pathways appear to play requisite roles in the mechanisms of RIC-related
      beneficial effects, and these pathways also display inseparable interactions with
      each other. So far, several hurdles lying ahead of clinical translation that
      remain to be settled, such as establishment of biomarkers, modification of RIC
      regimen, and deep understanding of underlying minutiae through which RIC exerts
      its powerful function. As this approach has garnered an increasing interest,
      herein, we aim to encapsulate an overview of the basic concept and postulated
      protective mechanisms of RIC, highlight the main findings from proof-of-concept
      clinical studies in various clinical scenarios, and also to discuss potential
      obstacles that remain to be conquered. More well designed and comprehensive
      experimental work or clinical trials are warranted in future research to confirm
      whether RIC could be utilized as a non-invasive, inexpensive and efficient
      adjunct therapeutic intervention method for multi-organ protection.

PMID- 30115819
TI  - High Temperature High Sensitivity Multipoint Sensing System Based on Three
      Cascade Mach-Zehnder Interferometers.
AB  - A temperature multipoint sensing system based on three cascade Mach-Zehnder
      interferometers (MZIs) is introduced. The MZIs with different lengths are
      fabricated based on waist-enlarged fiber bitapers. The fast Fourier
      transformation is applied to the overlapping transmission spectrum and the
      corresponding interference spectra can be obtained via the cascaded frequency
      spectrum based on the inverse Fourier transformation. By analyzing the drift of
      interference spectra, the temperature response sensitivities of 0.063 nm/ degrees
      C, 0.071 nm/ degrees C, and 0.059 nm/ degrees C in different furnaces can be
      detected from room temperature up to 1000  degrees C, and the temperature
      response at different regions can be measured through the sensitivity matrix
      equation. These results demonstrate feasibility of multipoint measurement, which
      also support that the temperature sensing system provides new solution to the MZI
      cascade problem.

PMID- 30115820
TI  - Putative Iron Acquisition Systems in Stenotrophomonas maltophilia.
AB  - Iron has been shown to regulate biofilm formation, oxidative stress response and
      several pathogenic mechanisms in Stenotrophomonas maltophilia. Thus, the present
      study is aimed at identifying various iron acquisition systems and iron sources
      utilized during iron starvation in S. maltophilia. The annotations of the
      complete genome of strains K279a, R551-3, D457 and JV3 through Rapid Annotations
      using Subsystems Technology (RAST) revealed two putative subsystems to be
      involved in iron acquisition: the iron siderophore sensor and receptor system and
      the heme, hemin uptake and utilization systems/hemin transport system. Screening
      for these acquisition systems in S. maltophilia showed the presence of all tested
      functional genes in clinical isolates, but only a few in environmental isolates.
      NanoString nCounter Elements technology, applied to determine the expression
      pattern of the genes under iron-depleted condition, showed significant expression
      for FeSR (6.15-fold), HmuT (12.21-fold), Hup (5.46-fold), ETFb (2.28-fold), TonB
      (2.03-fold) and Fur (3.30-fold). The isolates, when further screened for the
      production and chemical nature of siderophores using CAS agar diffusion (CASAD)
      and Arnows's colorimetric assay, revealed S. maltophilia to produce catechol-type
      siderophore. Siderophore production was also tested through liquid CAS assay and
      was found to be greater in the clinical isolate (30.8%) compared to environmental
      isolates (4%). Both clinical and environmental isolates utilized hemoglobin,
      hemin, transferrin and lactoferrin as iron sources. All data put together
      indicates that S. maltophilia utilizes siderophore-mediated and heme-mediated
      systems for iron acquisition during iron starvation. These data need to be
      further confirmed through several knockout studies.

PMID- 30115821
TI  - An In Vitro Estimation of the Cytotoxicity and Genotoxicity of Root Extract from
      Leonurus sibiricus L. Overexpressing AtPAP1 against Different Cancer Cell Lines.
AB  - As the current cancer treatment success rate is not sufficient, interest has
      grown in plants as possible sources of anti-cancer compounds. One such plant with
      a broad spectrum of activity is Lenourus sibiricus of the family Lamiaceae. This
      study investigates for the first time both the genotoxic and cytotoxic activities
      of TR (transformed) and AtPAP1 TR (with over-expression of transcriptional
      factor) root extracts of Lenourus sibiricus against various cancer cell lines
      (CCRF-CEM, K-562 and A549). Both tested extracts showed a cytotoxic effect on
      CCRF-CEM and K-562 cell lines, but strongest activity was observed for the AtPAP1
      TR extract. No cytotoxic effect was observed against the A549 cell line in the
      tested concentration range, and it was found that both tested extracts may induce
      apoptosis by decreasing mitochondrial membrane potential and inducing nDNA damage
      lesion in the TP53 region and mtDNA in ND1 (mitochondrially encoded NADH:
      ubiquinone oxidoreductase core subunit 1) and ND5 (mitochondrially encoded
      NADH:ubiquinone oxidoreductase core subunit 5) regions in K-562 and CCRF-CEM. Our
      results confirmed that TR and AtPAP1 TR root extracts from L. sibiricus are
      cytotoxic and genotoxic against different model cell lines (CCRF-CEM and K-562).
      However, the observed genotoxicity of both extracts needs to be confirmed by
      additional studies. These preclinical observations support the use of L.
      sibiricus with other pharmacological purposes.

PMID- 30115822
TI  - Graphene and Graphene-Based Nanomaterials for DNA Detection: A Review.
AB  - DNA detection with high sensitivity and specificity has tremendous potential as
      molecular diagnostic agents. Graphene and graphene-based nanomaterials, such as
      graphene nanopore, graphene nanoribbon, graphene oxide, and reduced graphene
      oxide, graphene-nanoparticle composites, were demonstrated to have unique
      properties, which have attracted increasing interest towards the application of
      DNA detection with improved performance. This article comprehensively reviews the
      most recent trends in DNA detection based on graphene and graphene-related
      nanomaterials. Based on the current understanding, this review attempts to
      identify the future directions in which the field is likely to thrive, and
      stimulate more significant research in this subject.

PMID- 30115824
TI  - Numerical Analysis and 1D/2D Sensitivity Study for Monolithic and Laminated
      Structural Glass Elements under Thermal Exposure.
AB  - Glass is largely used in architectural and engineering applications (i.e.,
      buildings and vehicles) as a structural material, especially in the form of
      laminated glass (LG) sections. To achieve adequate and controlled safety levels
      in these applications, the well-known temperature-dependent behavior of
      viscoelastic interlayers for LG sections should be properly accounted for during
      the design process. Furthermore, the materials' thermomechanical degradation with
      increases of temperature could severely affect the load-bearing performance of
      glass assemblies. In this context, uncoupled thermomechanical finite element (FE)
      numerical models could represent a robust tool and support for design engineers.
      Key input parameters and possible limits of the FE method, however, should be
      properly calibrated and assessed, so as to enable reliable estimations for the
      real behavior of glazing systems. In this paper, FE simulations are proposed for
      monolithic (MG) and LG specimens under radiant heating, based on one-dimensional
      (1D) and two-dimensional (2D) models. A special attention is focused on thermal
      effects, being representative of the first step for conventional uncoupled,
      thermomechanical analyses. Based on experimental results available in the
      literature, FE parametric studies are discussed, giving evidence of limits and
      issues due to several modeling assumptions. In particular, careful consideration
      is paid for various thermal material properties (conductivity, specific heat) and
      thermal boundaries (conductivity, emissivity), but also for other influencing
      parameters like the geometrical features of samples (thickness tolerances, cross
      sectional properties, etc.), the composition of LG sections (interlayer type,
      thickness), the loading pattern (heat transfer distribution) and the presence of
      additional mechanical restraints (i.e., supports of different materials).
      Comparative FE results are hence critically discussed, highlighting the major
      effects of such influencing parameters.

PMID- 30115823
TI  - Photosynthetic Accumulation of Lutein in Auxenochlorella protothecoides after
      Heterotrophic Growth.
AB  - In order to enhance lutein accumulation and to explain the reasons for the
      difference in lutein accumulation under photoautotrophic and heterotrophic
      conditions, different culture modes and the associated transcriptome profiles
      were investigated in Auxenochlorella protothecoides. The heterotrophic
      photoautotrophic transition culture mode was investigated for lutein
      accumulation, changing from organic carbon to increase biomass in dark
      fermentation to irradiation under nitrogen rich conditions. This strategy
      increased the lutein content 10 times along with chloroplast regeneration and
      little biomass loss in 48 h. The highest lutein productivity and production in
      the heterotrophic-photoautotrophic transition culture reached 12.36 mg/L/day and
      34.13 mg/L respectively within seven days. Furthermore, compared to the
      photoautotrophic conditions, most genes involved in lutein biosynthesis and
      photosystem generation were down-regulated during heterotrophic growth. By
      contrast, two beta-ring hydroxylases were transiently upregulated, while
      violaxanthin de-epoxidase and zeaxanthin epoxidase were mostly downregulated,
      which explained the extremely low lutein content of heterotrophic cells.
      Nevertheless, the lutein proportion in total carotenoids reached nearly 100%.
      This study is the first to our knowledge to report on a comparative transcriptome
      analysis of lutein biosynthesis, and it provides a promising strategy to boost
      lutein production in A. protothecoides.

PMID- 30115825
TI  - Youth and Adult Visitation and Physical Activity Intensity at Rural and Urban
      Parks.
AB  - Less physical activity among rural residents may contribute to rural-urban health
      disparities. Parks can be ideal community resources for promoting physical
      activity. This study compared park visitation and activity intensity at 15 urban
      and 15 rural parks matched for acreage and amenities. Parks were observed in the
      morning, afternoon, and evening on 4 days to determine number of visitors,
      activity intensity, and amenity use. A total of 5486 visitors were observed with
      no differences in percentages of males (55.5% vs. 53.9%) and females (44.5% vs.
      46.1%) or percentages of weekday (82.4% vs. 81.9%) and weekend (17.6% vs. 18.1%)
      visitors. The probability of visitors sitting was greater and in moderate
      intensity activity lower at rural parks. A greater proportion of children (25.0%
      vs. 14.5%) in rural parks, and teens in urban parks (8.0% vs. 69.6%), were
      observed on sport fields. A greater proportion of adults in urban areas (12.5%
      vs. 46.0%) were observed spectating sports. Greater proportions of rural children
      (10.9% vs. 3.5%), teens (34.1% vs. 12.4%), and adults (38.9% vs. 10.1%) were
      observed using shelters. Thus, when similar amenities are available, rural and
      urban parks are used differently, especially by youth. The urban park study
      results cannot be wholly applied to rural parks.

PMID- 30115826
TI  - Increased Plasma Brain-Derived Neurotrophic Factor 10.5 h after Intake of Whole
      Grain Rye-Based Products in Healthy Subjects.
AB  - It has previously been shown in short-term interventions that kernel-based whole
      grain (WG) rye products have beneficial effects on test markers related to
      obesity and type 2 diabetes (T2D). T2D increases the risk of several severe
      health issues, including declined cognitive functions. The protein brain-derived
      neurotrophic factor (BDNF) is suggested to be a potential biomarker for neuronal
      integrity. The aim of this study was to investigate the effect on plasma BDNF
      concentrations, 10.5 h after the intake of WG rye. Healthy young adults were
      provided late evening meals consisting of WG rye kernel-based bread (RKB) or a
      white wheat flour-based bread (reference product (WWB)), in a randomized cross
      over design. The BDNF concentrations were investigated at fasting in the morning
      10.5 h after single evening meals with RKB and WWB, and also after three
      consecutive evening meals with RKB and WWB, respectively. No difference was
      observed in the BDNF concentrations depending on the priming setting (p > 0.05).
      The RKB evening meals increased the BDNF concentrations by 27% at fasting (p =
      0.001), compared to WWB. The increase of BDNF after the RKB indicate that, in
      addition to anti-diabetic properties, the dietary fiber in WG rye may support
      neuronal integrity.

PMID- 30115827
TI  - Adherence to Nutrition and Physical Activity Cancer Prevention Guidelines and
      Development of Colorectal Adenoma.
AB  - Adherence to the American Cancer Society's (ACS) Nutrition and Physical Activity
      Cancer Prevention Guidelines is associated with reductions in overall cancer
      incidence and mortality, including site-specific cancers such as colorectal
      cancer. We examined the relationship between baseline adherence to the ACS
      guidelines and (1) baseline adenoma characteristics and (2) odds of recurrent
      colorectal adenomas over 3 years of follow-up. Cross-sectional and prospective
      analyses with a pooled sample of participants from the Wheat Bran Fiber (n = 503)
      and Ursodeoxycholic Acid (n = 854) trials were performed. A cumulative adherence
      score was constructed using baseline self-reported data regarding body size,
      diet, physical activity and alcohol consumption. Multivariable logistic
      regression demonstrated significantly reduced odds of having three or more
      adenomas at baseline for moderately adherent (odds ratio [OR] = 0.67, 95%
      confidence intervals [CI]: 0.46-0.99) and highly adherent (OR = 0.50, 95% CI:
      0.31-0.81) participants compared to low adherers (p-trend = 0.005). Conversely,
      guideline adherence was not associated with development of recurrent colorectal
      adenoma (moderate adherence OR = 1.16, 95% CI: 0.85-1.59, high adherence OR =
      1.23, 95% CI: 0.85-1.79).

PMID- 30115828
TI  - Tabla: A Proof-of-Concept Auscultatory Percussion Device for Low-Cost Pneumonia
      Detection.
AB  - Pneumonia causes the deaths of over a million people worldwide each year, with
      most occurring in countries with limited access to expensive but effective
      diagnostic methods, e.g., chest X-rays. Physical examination, the other major
      established method of diagnosis, suffers from several drawbacks, most notably low
      accuracy and high interobserver error. We sought to address this diagnostic gap
      by developing a proof-of-concept non-invasive device to identify the accumulation
      of fluid in the lungs (consolidation) characteristic of pneumonia. This device,
      named Tabla after the percussive instrument of the same name, utilizes the
      technique of auscultatory percussion; a percussive input sound is sent through
      the chest and recorded with a digital stethoscope for analysis. Tabla analyzes
      differences in sound transmission through the chest at audible frequencies as a
      marker for lung consolidation. This paper presents preliminary data from five
      pneumonia patients and eight healthy subjects. We demonstrate 92.3% accuracy in
      distinguishing between healthy subjects and patients with pneumonia after data
      analysis with a K-nearest neighbors algorithm. This prototype device is low cost
      and simple to implement and may offer a rapid and inexpensive method for
      pneumonia diagnosis appropriate for general use and in areas with limited medical
      infrastructure.

PMID- 30115830
TI  - Approaches to Assess Vitamin A Status in Settings of Inflammation: Biomarkers
      Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) Project.
AB  - The accurate estimation of vitamin A deficiency (VAD) is critical to informing
      programmatic and policy decisions that could have important public health
      implications. However, serum retinol and retinol binding protein (RBP)
      concentrations, two biomarkers often used to estimate VAD, are temporarily
      altered during the acute phase response, potentially overestimating the
      prevalence of VAD in populations with high levels of inflammation. In 22
      nationally-representative surveys, we examined (1) the association between C
      reactive protein (CRP) or alpha1-acid glycoprotein (AGP) and retinol or RBP, and
      (2) how different adjustment approaches for correcting for inflammation compare
      with one another. In preschool age children (PSC) and school age children (SAC),
      the association between inflammation and retinol and RBP was largely
      statistically significant; using the regression approach, adjustments for
      inflammation decreased the estimated prevalence of VAD compared to unadjusted VAD
      (range: -22.1 to -6.0 percentage points). In non-pregnant women of reproductive
      age (WRA), the association between inflammation and vitamin A biomarkers was
      inconsistent, precluding adjustments for inflammation. The burden of VAD can be
      overestimated if inflammation is not accounted for, and the regression approach
      provides a method for adjusting retinol and RBP for inflammation across the full
      range of concentrations in PSC and SAC.

PMID- 30115831
TI  - Exploring the Importance of Health Literacy for the Quality of Life in Patients
      with Heart Failure.
AB  - As with all other chronic noncommunicable diseases, adequate health literacy
      plays a key role in making the right decisions in the treatment of heart failure.
      Patients with heart failure and a lower health literacy have a reduced quality of
      life. A cross-sectional study among 200 patients with heart failure was conducted
      at a state university hospital in Belgrade, Serbia. The European Health Literacy
      Questionnaire, HLS-EU-Q47, was used to assess health literacy. Quality of life
      was measured with the generic SF-36 and the Minnesota Living with Heart Failure
      Questionnaire. Descriptive and analytical statistical analysis was applied. More
      than half of the respondents (64%) had limited health literacy. The lowest mean
      health literacy index (28.01 +/- 9.34) was within the disease prevention
      dimension, where the largest number of respondents showed limited health literacy
      (70%). Our patients had a poorer quality of life in the physical dimension, and
      the best scores were identified in the emotional role and social functioning.
      Health literacy was highly statistically significant and an independent predictor
      of quality of life (physical, mental, and total quality of life). Improving
      health literacy can lead to better decisions in the treatment of disease and
      quality of life in heart failure patients.

PMID- 30115832
TI  - An Associative Memory Approach to Healthcare Monitoring and Decision Making.
AB  - The rapid proliferation of connectivity, availability of ubiquitous computing,
      miniaturization of sensors and communication technology, have changed healthcare
      in all its areas, creating the well-known healthcare paradigm of e-Health. In
      this paper, an embedded system capable of monitoring, learning and classifying
      biometric signals is presented. The machine learning model is based on
      associative memories to predict the presence or absence of coronary artery
      disease in patients. Classification accuracy, sensitivity and specificity results
      show that the performance of our proposal exceeds the performance achieved by
      each of the fifty widely known algorithms against which it was compared.

PMID- 30115829
TI  - An Update on Protein, Leucine, Omega-3 Fatty Acids, and Vitamin D in the
      Prevention and Treatment of Sarcopenia and Functional Decline.
AB  - Aging is associated with sarcopenia and functional decline, leading to frailty
      and disability. As a modifiable risk factor, nutrition may represent a target for
      preventing or postponing the onset of these geriatric conditions. Among
      nutrients, high-quality protein, leucine, vitamin D, and omega-3 polyunsaturated
      fatty acids (n-3 PUFA) are of particular interest for their demonstrated effects
      on skeletal muscle health. This narrative review aims to examine the recent
      observational and interventional evidence on the associations and the role of
      these nutrients in the muscle mass, strength, mobility, and physical function of
      free-living older adults, who are either healthy or at risk of frailty. Recent
      evidence supports a higher protein intake recommendation of 1.0-1.2 g/kg/day in
      healthy older adults; an evenly distributed mealtime protein intake or minimal
      protein per meal may be beneficial. In addition, vitamin D supplementation of 800
      1000 IU, particularly when vitamin D status is low, and doses of ~3 g/day of n-3
      PUFA may be favorable for physical function, muscle mass, and strength. Reviewed
      studies are highly heterogenous, yet the quantity, quality, and timing of intakes
      should be considered when designing intervention studies. Combined protein,
      leucine, vitamin D, and n-3 PUFA supplements may convey added benefits and may
      represent an intervention strategy in the prevention of sarcopenia and functional
      decline.

PMID- 30115833
TI  - Drivers Analysis of CO2 Emissions from the Perspective of Carbon Density: The
      Case of Shandong Province, China.
AB  - Against the backgrounds of emission reduction targets promised by China, it is
      crucial to explore drivers of CO2 emissions comprehensively for policy making. In
      this study, Shandong Province in China is taken as an example to investigate
      drivers in carbon density by using an extended Kaya identity and a logarithmic
      mean Divisia index model (LMDI) with two layers. It is concluded that there are
      eight positive driving factors of carbon density during 2000-2015, including
      traffic congestion, land urbanization, etc., and seven negative driving factors
      comprising energy intensity, economic structure, etc. Among these factors,
      economic growth and energy intensity are the main positive and negative driving
      factor, respectively. The contribution rate of traffic congestion and land
      urbanization is gradually increasing. Meanwhile, 15 driving factors are divided
      into five categories. Economic effect and urbanization effect are the primary
      positive drivers. Contrarily, energy intensity effect, structural effect, and
      scale effect contribute negative effects to the changes in carbon density. In the
      four stages, the contribution of urbanization to carbon density is inverted U.
      Overall, the results and suggestions can give support to decision maker to draw
      up relevant government policy.

PMID- 30115835
TI  - Exploring the Relationship between Ridesharing and Public Transit Use in the
      United States.
AB  - Car travel accounts for the largest share of transportation-related greenhouse
      gas emissions in the United States (U.S.), leading to serious air pollution and
      negative health effects; approximately 76.3% of car trips are single-occupant. To
      reduce the negative externalities of cars, ridesharing and public transit are
      advocated as cost-effective and more environmentally sustainable alternatives. A
      better understanding of individuals' uses of these two transport modes and their
      relationship is important for transport operators and policymakers; however, it
      is not well understood how ridesharing use is associated with public transit use.
      The objective of this study is to examine the relationships between the frequency
      and probability of ridesharing use and the frequency of public transit use in the
      U.S. Zero-inflated negative binomial regression models were employed to
      investigate the associations between these two modes, utilizing individual-level
      travel frequency data from the 2017 National Household Travel Survey. The survey
      data report the number of times the respondent had used ridesharing and public
      transit in the past 30 days. The results show that, generally, a one-unit
      increase in public transit use is significantly positively related to a 1.2%
      increase in the monthly frequency of ridesharing use and a 5.7% increase in the
      probability of ridesharing use. Additionally, the positive relationship between
      ridesharing and public transit use was more pronounced for people who live in
      areas with a high population density or in households with fewer vehicles. These
      findings highlight the potential for integrating public transit and ridesharing
      systems to provide easier multimodal transportation, promote the use of both
      modes, and enhance sustainable mobility, which are beneficial for the environment
      and public health.

PMID- 30115836
TI  - A Bio-inspired Motivational Decision Making System for Social Robots Based on the
      Perception of the User.
AB  - Nowadays, many robotic applications require robots making their own decisions and
      adapting to different conditions and users. This work presents a biologically
      inspired decision making system, based on drives, motivations, wellbeing, and
      self-learning, that governs the behavior of the robot considering both internal
      and external circumstances. In this paper we state the biological foundations
      that drove the design of the system, as well as how it has been implemented in a
      real robot. Following a homeostatic approach, the ultimate goal of the robot is
      to keep its wellbeing as high as possible. In order to achieve this goal, our
      decision making system uses learning mechanisms to assess the best action to
      execute at any moment. Considering that the proposed system has been implemented
      in a real social robot, human-robot interaction is of paramount importance and
      the learned behaviors of the robot are oriented to foster the interactions with
      the user. The operation of the system is shown in a scenario where the robot Mini
      plays games with a user. In this context, we have included a robust user
      detection mechanism tailored for short distance interactions. After the learning
      phase, the robot has learned how to lead the user to interact with it in a
      natural way.

PMID- 30115837
TI  - Action-Centered Exposure Therapy (ACET): A New Approach to the Use of Virtual
      Reality to the Care of People with Post-Traumatic Stress Disorder.
AB  - Post-Traumatic Stress Disorder (PTSD) can be seen as the result of dysfunctional
      beliefs that associate stimuli with a danger or a threat leading to anxious
      reactions. Exposure therapy is so far considered to be the most effective
      treatment, and research suggests that it is mainly based on a habituation
      process. Based on learning theories, it appears that a passive systemic exposure
      to traumatic stimuli should not be the best option for the treatment of PTSD. We
      hypothesis that an active learning of safer and healthier coping strategies
      combined with systematic exposure should be more effective in reducing the
      psychological distress associated with PTSD. In this paper, we describe the
      theoretical foundations of this approach that focuses on the action and activity
      of the patient in his or her exposure environment. In this approach, we take
      advantage of Virtual Reality technologies and learning mechanics of serious games
      to allow the patient to learn new safe associations while promoting the
      empowerment. We named this action-centered exposure therapy (ACET). This approach
      exploits behaviorism, cognitivism, and constructivism learning theories. With the
      different benefits of virtual reality technologies, this approach would easily
      integrate with in-virtuo exposure therapy and would allow us to exploit as much
      as possible the enormous potential of these technologies. As a first step toward
      validation, we present a case study that supports the ACET approach.

PMID- 30115834
TI  - Hallmarks of Cancer-Related Newly Prognostic Factors of Oral Squamous Cell
      Carcinoma.
AB  - Head and neck cancer, including oral squamous cell carcinoma (OSCC), is the sixth
      leading malignancy worldwide. OSCC is an aggressive tumor and its prognosis has
      exhibited little improvement in the last three decades. Comprehensive elucidation
      of OSCC's molecular mechanism is imperative for early detection and treatment,
      improving patient survival. Based on broadly accepted notions, OSCC arises from
      multiple genetic alterations caused by chronic exposure to carcinogens. In 2011,
      research revealed 10 key alterations fundamental to cancer cell development:
      sustaining proliferative signaling, evading growth suppressors, avoiding immune
      destruction, activating invasion and metastasis, tumor-promoting inflammation,
      enabling replicative immortality, inducing angiogenesis, genome instability and
      mutation, resisting cell death, and deregulating energetics. This review
      describes molecular pathological findings on conventional and novel hallmarks of
      OSCC prognostic factors. In addition, the review summarizes the functions and
      roles of several molecules as novel OSCC prognosticators.

PMID- 30115838
TI  - Suzuki-Type Cross-Coupling Reaction of Unprotected 3-Iodoindazoles with Pinacol
      Vinyl Boronate: An Expeditive C-3 Vinylation of Indazoles under Microwave
      Irradiation.
AB  - Herein we report an expeditive C-3 vinylation of unprotected 3-iodoindazoles
      under microwave irradiation. Ten C-5 substituted 3-vinylindazole derivatives,
      nine of them novel, were synthesized through this method, which proceeds in
      moderate to excellent yields starting from C-5 substituted 3-iodoindazole
      derivatives. In all cases, the C-3 vinylated derivative was the only isolated
      product. This methodology allows access to 3-vinylated indazoles selectively and
      directly without the need of N-protection. 3-Vinylindazoles could be interesting
      synthetic intermediates allowing access to biologically active molecules.

PMID- 30115839
TI  - The Protean Acremonium. A. sclerotigenum/egyptiacum: Revision, Food Contaminant,
      and Human Disease.
AB  - Acremonium is known to be regularly isolated from food and also to be a cause of
      human disease. Herein, we resolve some sources of confusion that have strongly
      hampered the accurate interpretation of these and other isolations. The recently
      designated type species of the genus Acremonium, A. alternatum, is known only
      from a single isolate, but it is the closest known relative of what may be one of
      the planet's most successful organisms, Acremonium sclerotigenum/egyptianum,
      shown herein to be best called by its earliest valid name, A. egyptiacum. The
      sequencing of ribosomal internal transcribed spacer (ITS) regions, actin genes,
      or both for 72 study isolates within this group allowed the full range of
      morphotypes and ITS barcode types to be elucidated, along with information on
      temperature tolerance and habitat. The results showed that nomenclatural
      confusion and frequent misidentifications facilitated by morphotaxonomy, along
      with misidentified early sequence deposits, have obscured the reality that this
      species is, in many ways, the definitive match of the historical concept of
      Acremonium: a pale orange or dull greenish-coloured monophialidic hyphomycete,
      forming cylindrical, ellipsoidal, or obovoid conidia in sticky heads or obovoid
      conidia in dry chains, and acting ecologically as a soil organism, marine
      organism, plant pathogen, plant endophyte, probable insect pathogen, human
      opportunistic pathogen, food contaminant, probable dermatological communicable
      disease agent, and heat-tolerant spoilage organism. Industrially, it is already
      in exploratory use as a producer of the antibiotic ascofuranone, active against
      trypanosomes, cryptosporidia, and microsporidia, and additional applications are
      in development. The genus-level clarification of the phylogeny of A. egyptiacum
      shows other historic acremonia belong to separate genera, and two are here
      described, Parasarocladium for the Acremonium radiatum complex and Kiflimonium
      for the Acremonium curvulum complex.

PMID- 30115840
TI  - Characterization of Nanospheres Containing Zanthoxylum riedelianum Fruit
      Essential Oil and Their Insecticidal and Deterrent Activities against Bemisia
      tabaci (Hemiptera: Aleyrodidae).
AB  - The aim of our study was to produce and characterize poly-epsilon-caprolactone
      (PCL) nanospheres containing essential oils from Zanthoxylum riedelianum fruit
      and to evaluate their stability gains as well as their insecticidal and deterrent
      activities against whitefly (Bemisia tabaci). The PCL nanospheres exhibited a
      homogeneous spherical morphology, with particle diameters between 106.7 nm and
      129.2 nm, pH of approximately 6, zeta potential (ZP) lower than -19.0 mV and
      encapsulation efficiency higher than 98%. Only 43% of the nanoencapsulated
      essential oil (NSEO) was degraded in response to ultraviolet light, whereas the
      essential oil (EO) degraded by 76% over the same period. In a free-choice test,
      the NSEO and EO reduced the number of whitefly eggs by approximately 70%. NSEO
      and EO at 1.5% killed 82.87% and 91.23% of 2nd-instar nymphs of whitefly,
      respectively. Although NSEO displayed lower insecticidal activity, it offers a
      greater advantage over the free EO, due to protection conferred by polymer
      against photodegradation. Therefore, its usage may optimize the maintenance of
      essential oils in the field through photoprotection and controlled release. Our
      results suggest that the EO of Z. riedelianum fruit can be used for B. tabaci
      management strategy; nevertheless, the benefits of NSEO require further
      evaluation at the field level.

PMID- 30115842
TI  - Mechanical Properties of Hybrid Ultra-High Performance Engineered Cementitous
      Composites Incorporating Steel and Polyethylene Fibers.
AB  - This paper presents the authors' newly developed hybrid ultra-high performance
      (HUHP) engineered cementitious composite (ECC) with steel (ST) and polyethylene
      (PE) fibers. From this point on it will be referred to as HUHP-ECC. The volumes
      of steel and PE fibers were adjusted to obtain different mechanical properties,
      including compressive strength, tensile, and flexural properties. We found that
      tensile and flexural properties, including bending strength and ductility
      indexes, increased with higher PE fiber amounts but reduced with the increased ST
      fiber volume. Notably, the compressive strength had the opposite tendency and
      decreased with increases in the PE volume. The ST fiber had a significantly
      positive effect on the compressive strength. The fluidity of HUHP-ECC improved
      with the increasing amount of ST fiber. The pseudo strain-hardening (PSH) values
      for all the HUHP-ECC mixtures were used to create an index indicating the ability
      of strain capacity; thus, the PSH values were calculated to explain the ductility
      of HUHP-ECC with different fiber volumes. Finally, the morphology of PE and ST
      fibers at the fracture surface was observed by an environmental scanning electron
      microscope (ESEM).

PMID- 30115841
TI  - Biopesticide Activity from Drimanic Compounds to Control Tomato Pathogens.
AB  - Tomato crops can be affected by several infectious diseases produced by bacteria,
      fungi, and oomycetes. Four phytopathogens are of special concern because of the
      major economic losses they generate worldwide in tomato production; Clavibacter
      michiganensis subsp. michiganensis and Pseudomonas syringae pv. tomato, causative
      agents behind two highly destructive diseases, bacterial canker and bacterial
      speck, respectively; fungus Fusarium oxysporum f. sp. lycopersici that causes
      Fusarium Wilt, which strongly affects tomato crops; and finally, Phytophthora
      spp., which affect both potato and tomato crops. Polygodial (1), drimenol (2),
      isonordrimenone (3), and nordrimenone (4) were studied against these four
      phytopathogenic microorganisms. Among them, compound 1, obtained from Drimys
      winteri Forst, and synthetic compound 4 are shown here to have potent activity.
      Most promisingly, the results showed that compounds 1 and 4 affect Clavibacter
      michiganensis growth at minimal inhibitory concentrations (MIC) values of 16 and
      32 ug/mL, respectively, and high antimycotic activity against Fusarium oxysporum
      and Phytophthora spp. with MIC of 64 ug/mL. The results of the present study
      suggest novel treatment alternatives with drimane compounds against bacterial and
      fungal plant pathogens.

PMID- 30115845
TI  - Indoor Visual Positioning Aided by CNN-Based Image Retrieval: Training-Free, 3D
      Modeling-Free.
AB  - Indoor localization is one of the fundamentals of location-based services (LBS)
      such as seamless indoor and outdoor navigation, location-based precision
      marketing, spatial cognition of robotics, etc. Visual features take up a dominant
      part of the information that helps human and robotics understand the environment,
      and many visual localization systems have been proposed. However, the problem of
      indoor visual localization has not been well settled due to the tough trade-off
      of accuracy and cost. To better address this problem, a localization method based
      on image retrieval is proposed in this paper, which mainly consists of two parts.
      The first one is CNN-based image retrieval phase, CNN features extracted by pre
      trained deep convolutional neural networks (DCNNs) from images are utilized to
      compare the similarity, and the output of this part are the matched images of the
      target image. The second one is pose estimation phase that computes accurate
      localization result. Owing to the robust CNN feature extractor, our scheme is
      applicable to complex indoor environments and easily transplanted to outdoor
      environments. The pose estimation scheme was inspired by monocular visual
      odometer, therefore, only RGB images and poses of reference images are needed for
      accurate image geo-localization. Furthermore, our method attempts to use
      lightweight datum to present the scene. To evaluate the performance, experiments
      are conducted, and the result demonstrates that our scheme can efficiently result
      in high location accuracy as well as orientation estimation. Currently the
      positioning accuracy and usability enhanced compared with similar solutions.
      Furthermore, our idea has a good application foreground, because the algorithms
      of data acquisition and pose estimation are compatible with the current state of
      data expansion.

PMID- 30115843
TI  - Treatment of Invasive Candidiasis: A Narrative Review.
AB  - Invasive candidiasis occurs frequently in hospitalized patients, and is
      associated with high mortality rates due to delays in recognition and initiation
      of appropriate antifungals. Management of invasive candidiasis must take into
      account multiple host, pathogen, and drug-related factors, including the site of
      infection, host immune status, severity of sepsis, resistance and tolerance to
      antifungal agents, biofilm formation, and pharmacokinetic/pharmacodynamic
      considerations. Recent treatment directives have been shaped by the widespread
      introduction of echinocandins, highly potent and safe antifungals, into clinical
      use, as well as important changes in drug susceptibility patterns and the
      emergence of known and novel drug-resistant Candida species. Advances in
      molecular diagnostics have the potential to guide early targeted treatment of
      high-risk patients.

PMID- 30115844
TI  - Two New Polyphenol Oxidase Genes of Tea Plant (Camellia sinensis) Respond
      Differentially to the Regurgitant of Tea Geometrid, Ectropis obliqua.
AB  - Polyphenol oxidases (PPOs) have been reported to play an important role in
      protecting plants from attacks by herbivores. Though PPO genes in other plants
      have been extensively studied, research on PPO genes in the tea plant (Camellia
      sinensis) is lacking. In particular, which members of the PPO gene family elicit
      the defense response of the tea plant are as yet unknown. Here, two new PPO
      genes, CsPPO1 and CsPPO2, both of which had high identity with PPOs from other
      plants, were obtained from tea leaves. The full length of CsPPO1 contained an
      open reading frame (ORF) of 1740 bp that encoded a protein of 579 amino acids,
      while CsPPO2 contained an ORF of 1788 bp that encoded a protein of 595 amino
      acids. The deduced CsPPO1 and CsPPO2 proteins had calculated molecular masses of
      64.6 and 65.9 kDa; the isoelectric points were 6.94 and 6.48, respectively. The
      expression products of recombinant CsPPO1 and CsPPO2 in Escherichia coli were
      about 91 and 92 kDa, respectively, but the recombinant proteins existed in the
      form of an inclusion body. Whereas CsPPO1 is highly expressed in stems, CsPPO2 is
      highly expressed in roots. Further results showed that the expression of CsPPO1
      and CsPPO2 was wound- and Ectropis obliqua-induced, and that regurgitant, unlike
      treatment with wounding plus deionized water, significantly upregulated the
      transcriptional expression of CsPPO2 but not of CsPPO1. The difference between
      regurgitant and wounding indicates that CsPPO2 may play a more meaningful
      defensive role against E. obliqua than CsPPO1. Meanwhile, we found the active
      component(s) of the regurgitant elicited by the expression of CsPPO may contain
      small molecules (under 3-kDa molecular weight). These conclusions advance the
      understanding of the biological function of two new PPO genes and show that one
      of these, CsPPO2, may be a promising gene for engineering tea plants that are
      resistant to E. obliqua.

PMID- 30115847
TI  - Analysis of Favorable Process Conditions for the Manufacturing of Thin-Wall
      Pieces of Mild Steel Obtained by Wire and Arc Additive Manufacturing (WAAM).
AB  - One of the challenges in additive manufacturing (AM) of metallic materials is to
      obtain workpieces free of defects with excellent physical, mechanical, and
      metallurgical properties. In wire and arc additive manufacturing (WAAM) the
      influences of process conditions on thermal history, microstructure and resultant
      mechanical and surface properties of parts must be analyzed. In this work, 3D
      metallic parts of mild steel wire (American Welding Society-AWS ER70S-6) are
      built with a WAAM process by depositing layers of material on a substrate of a
      S235 JR steel sheet of 3 mm thickness under different process conditions, using
      as welding process the gas metal arc welding (GMAW) with cold metal transfer
      (CMT) technology, combined with a positioning system such as a computer numerical
      controlled (CNC) milling machine. Considering the hardness profiles, the
      estimated ultimate tensile strengths (UTS) derived from the hardness measurements
      and the microstructure findings, it can be concluded that the most favorable
      process conditions are the ones provided by CMT, with homogeneous hardness
      profiles, good mechanical strengths in accordance to conditions defined by
      standard, and without formation of a decohesionated external layer; CMT
      Continuous is the optimal option as the mechanical properties are better than
      single CMT.

PMID- 30115846
TI  - Recent Advances by In Silico and In Vitro Studies of Amyloid-beta 1-42 Fibril
      Depicted a S-Shape Conformation.
AB  - The amyloid-beta 1-42 (Abeta1-42) peptide is produced by proteolytic cleavage of
      the amyloid precursor protein (APP) by sequential reactions that are catalyzed by
      gamma and beta secretases. Abeta1-42, together with the Tau protein are two
      principal hallmarks of Alzheimer's disease (AD) that are related to disease
      genesis and progression. Abeta1-42 possesses a higher aggregation propensity, and
      it is able to form fibrils via nucleated fibril formation. To date, there are
      compounds available that prevent Abeta1-42 aggregation, but none have been
      successful in clinical trials, possibly because the Abeta1-42 structure and
      aggregation mechanisms are not thoroughly understood. New molecules have been
      designed, employing knowledge of the Abeta1-42 structure and are based on
      preventing or breaking the ionic interactions that have been proposed for
      formation of the Abeta1-42 fibril U-shaped structure. Recently, a new Abeta1-42
      fibril S-shaped structure was reported that, together with its aggregation and
      catalytic properties, could be helpful in the design of new inhibitor molecules.
      Therefore, in silico and in vitro methods have been employed to analyze the
      Abeta1-42 fibril S-shaped structure and its aggregation to obtain more accurate
      Abeta1-42 oligomerization data for the design and evaluation of new molecules
      that can prevent the fibrillation process.

PMID- 30115848
TI  - miR-1246 Targets CCNG2 to Enhance Cancer Stemness and Chemoresistance in Oral
      Carcinomas.
AB  - MiRNAs have been recognized as crucial components in carcinogenesis, but whether
      miR-1246 affects the cancer stemness and drug resistance in oral squamous cell
      carcinoma (OSCC) has not been fully understood and its downstream targets still
      need to be unraveled. In the present work, we employed miRNAs RT-PCR analysis to
      evaluate the expression of miR-1246 in tumor tissues and oral cancer stem cells
      (OCSC). Stemness phenotypes, including self-renewal, migration, invasion, colony
      formation capacities, and in vivo oncogenicity of oral cancer cells following
      transfected with miR-1246 inhibitors or mimics were examined. Our results
      suggested that the expression level of miR-1246 was significantly upregulated in
      the tumor tissues and OCSC. Kaplan-Meier survival analysis of OSCC patients with
      high levels of miR-1246 had the worst survival rate compared to their low
      expression counterparts. Inhibition of miR-1246 in OCSC significantly reduced the
      stemness hallmarks, while overexpression of miR-1246 enhanced these
      characteristics. Moreover, we showed that downregulation of miR-1246 decreased
      chemoresistance. In addition, we verified that miR-1246-inhibited CCNG2
      contributed to the cancer stemness of OSCC. These results demonstrated the
      significance of miR-1246 in the regulation of OSCC stemness. Targeting miR-1246
      CCNG2 axis may be beneficial to suppress cancer relapse and metastasis in OSCC
      patients.

PMID- 30115850
TI  - Synthesis and Coordination Behavior of a Flexible Bis(phosphinoferrocene) Ligand.
AB  - A symmetrical flexible bis(phosphinoferrocene) derivative, viz. bis[1'
      (diphenylphosphino)ferrocenyl]methane (1), was prepared and studied as a ligand
      in Pd(II) and Au(I) complexes. The reactions of 1 with [PdCl2(cod)] (cod =
      cycloocta-1,5-diene) and [Pd(MU-Cl)(LNC)]2 (LNC = [2-(dimethylamino
      kappaN)methyl]phenyl-kappaC1) produced bis(phosphine) complex trans-[PdCl2(1
      kappa2P,P')] (4), wherein the ligand spans trans positions in the square-planar
      coordination sphere of Pd(II) and the tetranuclear, P,P-bridged complex
      [(MU(P,P')-1){PdCl(LNC)}2] (5), respectively. In reactions with the Au(I)
      precursors [AuCl(tht)] and [Au(tht)2][SbF6] (tht = tetrahydrothiophene), ligand 1
      gave rise to tetranuclear Au2Fe2 complex [(MU(P,P')-1)(AuCl)2] (6) and to
      symmetrical macrocyclic tetramer [Au4(MU(P,P')-1)4][SbF6]4 (7). All compounds
      were characterized by spectroscopic methods. In addition, the structures of
      compound 1, its synthetic precursor bis[1'
      (diphenylphosphino)ferrocenyl]methanone (3), and all aforementioned Pd(II) and
      Au(I) complexes were determined by single-crystal X-ray diffraction analysis
      (some in solvated form).

PMID- 30115851
TI  - Synstable Fusion: A Network-Based Algorithm for Estimating Driver Genes in Fusion
      Structures.
AB  - Gene fusion structure is a class of common somatic mutational events in cancer
      genomes, which are often formed by chromosomal mutations. Identifying the driver
      gene(s) in a fusion structure is important for many downstream analyses and it
      contributes to clinical practices. Existing computational approaches have
      prioritized the importance of oncogenes by incorporating prior knowledge from
      gene networks. However, different methods sometimes suffer different weaknesses
      when handling gene fusion data due to multiple issues such as fusion gene
      representation, network integration, and the effectiveness of the evaluation
      algorithms. In this paper, Synstable Fusion (SYN), an algorithm for
      computationally evaluating the fusion genes, is proposed. This algorithm uses
      network-based strategy by incorporating gene networks as prior information, but
      estimates the driver genes according to the destructiveness hypothesis. This
      hypothesis balances the two popular evaluation strategies in the existing
      studies, thereby providing more comprehensive results. A machine learning
      framework is introduced to integrate multiple networks and further solve the
      conflicting results from different networks. In addition, a synchronous stability
      model is established to reduce the computational complexity of the evaluation
      algorithm. To evaluate the proposed algorithm, we conduct a series of experiments
      on both artificial and real datasets. The results demonstrate that the proposed
      algorithm performs well on different configurations and is robust when altering
      the internal parameter settings.

PMID- 30115849
TI  - Long-Term Effects of Cold on Growth, Development and Yield of Narrow-Leaf Lupine
      May Be Alleviated by Seed Hydropriming or Butenolide.
AB  - In this article, the effects of cold on the development of Lupine angustifolius
      and the possibility of mitigating it, via seed hydropriming or pre-treatment with
      butenolide (10-6 M-10-4 M), are investigated in two cultivars, differing in their
      ability to germinate at low temperature. Physiological background of plant
      development after cold stress was investigated in imbibed seeds. For the first
      four weeks, the seedlings grew at 7  degrees C or 13  degrees C. Seeds well
      germinating at 7  degrees C demonstrated higher activity of alpha-amylase and
      higher levels of gibberellins, IAA and kinetin. Germination ability at low
      temperature correlated with dehydrogenase activity and membrane permeability.
      Seed pre-treatment improved germination at low temperature by decreasing abscisic
      acid content. Seed hydropriming alleviated cold effects on plant development rate
      and yield, while butenolide accelerated vegetative development but delayed the
      generative phase. Potential seed yield may be predicted based on the seed
      germination vigour and the photosynthetic efficiency measured before flowering.

PMID- 30115852
TI  - Functional Linkage of RKIP to the Epithelial to Mesenchymal Transition and
      Autophagy during the Development of Prostate Cancer.
AB  - Raf kinase inhibitor protein (RKIP) plays a critical role in many signaling
      pathways as a multi-functional adapter protein. In particular, the loss of RKIP's
      function in certain types of cancer cells results in epithelial to mesenchymal
      transition (EMT) and the promotion of cancer metastasis. In addition, RKIP
      inhibits autophagy by modulating LC3-lipidation and mTORC1. How the RKIP
      dependent inhibition of autophagy is linked to EMT and cancer progression is
      still under investigation. In this study, we investigated the ways by which RKIP
      interacts with key gene products in EMT and autophagy during the progression of
      prostate cancer. We first identified the gene products of interest using the
      corresponding gene ontology terms. The weighted-gene co-expression network
      analysis (WGCNA) was applied on a gene expression dataset from three groups of
      prostate tissues; benign prostate hyperplasia, primary and metastatic cancer. We
      found two modules of highly co-expressed genes, which were preserved in other
      independent datasets of prostate cancer tissues. RKIP showed potentially novel
      interactions with one EMT and seven autophagy gene products (TGFBR1; PIK3C3,
      PIK3CB, TBC1D25, TBC1D5, TOLLIP, WDR45 and WIPI1). In addition, we identified
      several upstream transcription modulators that could regulate the expression of
      these gene products. Finally, we verified some RKIP novel interactions by co
      localization using the confocal microscopy analysis in a prostate cancer cell
      line. To summarize, RKIP interacts with EMT and autophagy as part of the same
      functional unit in developing prostate cancer.

PMID- 30115853
TI  - Consumption of Cherry out of Season Changes White Adipose Tissue Gene Expression
      and Morphology to a Phenotype Prone to Fat Accumulation.
AB  - The aim of this study was to determine whether the consumption of cherry out of
      its normal harvest photoperiod affects adipose tissue, increasing the risk of
      obesity. Fischer 344 rats were held over a long day (LD) or a short day (SD), fed
      a standard diet (STD), and treated with a cherry lyophilizate (CH) or vehicle
      (VH) (n = 6). Biometric measurements, serum parameters, gene expression in white
      (RWAT) and brown (BAT) adipose tissues, and RWAT histology were analysed. A
      second experiment with similar conditions was performed (n = 10) but with a
      cafeteria diet (CAF). In the STD experiment, Bmal1 and Cry1 were downregulated in
      the CHSD group compared to the VHSD group. Pparalpha expression was downregulated
      while Ucp1 levels were higher in the BAT of the CHSD group compared to the VHSD
      group. In the CAF-fed rats, glucose and insulin serum levels increased, and the
      expression levels of lipogenesis and lipolysis genes in RWAT were downregulated,
      while the adipocyte area increased and the number of adipocytes diminished in the
      CHSD group compared to the VHSD group. In conclusion, we show that the
      consumption of cherry out of season influences the metabolism of adipose tissue
      and promotes fat accumulation when accompanied by an obesogenic diet.

PMID- 30115854
TI  - The Effect of Diet on Improved Endurance in Male C57BL/6 Mice.
AB  - The consumption of fruits and vegetables appears to help with maintaining an
      adequate level of exercise and improves endurance. However, the mechanisms that
      are involved in this process are not well understood. In the current study, the
      impact of diets enriched in fruits and vegetables (GrandFusion(r)) on exercise
      endurance was examined in a mouse model. GrandFusion (GF) diets increased
      mitochondrial DNA and enzyme activity, while they also stimulated mitochondrial
      mRNA synthesis in vivo. GF diets increased both the mRNA expression of factors
      involved in mitochondrial biogenesis, peroxisome proliferator-activated receptor
      gamma coactivator 1 alpha (PGC-1alpha), mitochondrial transcription factor A
      (Tfam), estrogen-related receptor alpha (ERRalpha), nuclear respiratory factor 1
      (NRF-1), cytochrome c oxidase IV (COXIV) and ATP synthase (ATPsyn). Mice treated
      with GF diets showed an increase in running endurance, rotarod perseverance and
      grip strength when compared to controls who were on a regular diet. In addition,
      GF diets increased the protein expression of phosphorylated AMP-activated protein
      kinase (AMPK), sirtuin 1 (SIRT1), PGC-1alpha and peroxisome proliferator
      activated receptor delta (PPAR-delta), which was greater than exercise-related
      changes. Finally, GF reduced the expression of phosphorylated ribosomal protein
      S6 kinase 1 (p-S6K1) and decreased autophagy. These results demonstrate that GF
      diets enhance exercise endurance, which is mediated via mitochondrial biogenesis
      and function.

PMID- 30115855
TI  - In Vivo Analysis of miR-34a Regulated Glucose Metabolism Related Genes in
      Megalobrama amblycephala.
AB  - The Megalobrama amblycephala (M. amblycephala) is one of the most important
      economic freshwater fish in China. The molecular mechanism under the glucose
      intolerance responses which affects the growth performance and feed utilization
      is still confused. miR-34a was reported as a key regulator in the glucose
      metabolism, but how did the miR-34a exert its function in the metabolism of
      glucose/insulin in M. amblycephala was still unclear. In this study, we
      intraperitoneally injected the miR-34a inhibitor (80 nmol/100 g body weight) into
      M. amblycephala (fed with high starch diet, 45% starch) for 12 h, and then
      analyzed the gene expression profiling in livers by RNA-seq. The results showed
      that miR-34a expression in M. amblycephala livers was inhibited by injection of
      miR-34a inhibitor, and a total of 2212 differentially expressed genes (DEGs) were
      dysregulated (including 1183 up- and 1029 downregulated DEGs). Function
      enrichment analysis of DEGs showed that most of them were enriched in the
      peroxisome proliferator-activated receptor (PPAR), insulin, AMP-activated protein
      kinase (AMPK) and janus kinase/signal transducers and activators of transcription
      (JAK/STAT) signaling pathways, which were all associated with the glucose/lipid
      metabolic and biosynthetic processes. In addition, we examined and verified the
      differential expression levels of some genes involved in AMPK signaling pathway
      by qRT-PCR. These results demonstrated that the inhibition of miR-34a might
      regulate glucose metabolism in M. amblycephala through downstream target genes.

PMID- 30115858
TI  - Comparative Research on the Rebound Effect in Direct Electromagnetic Forming and
      Indirect Electromagnetic Forming with an Elastic Medium.
AB  - In the process of electromagnetic forming (EMF), the rebound effect caused by
      high speed collision between sheet and die will affect the fittability, which
      results in a bad forming quality of workpiece. In this paper, finite element
      models of direct EMF and indirect EMF with an elastic medium are established, the
      influence factors of fittability in indirect EMF are studied, the two forming
      processes are compared, and the mechanisms of reduced rebound effect in indirect
      EMF are revealed. The results show that: in indirect EMF, with the increase of
      the discharging voltage or thickness of rubber, the fittability increases and
      then decreases; when the thickness of driver plate is equal to the skin depth of
      the driver plate, the fittability is the best. The optimal process parameters of
      indirect EMF are as follows: the discharging voltage is 10 kV, the thickness of
      the rubber is 20 mm and the thickness of driver plate is 2 mm. The rebound effect
      in indirect EMF is reduced compared with direct EMF for the following reasons:
      the impact force caused by the collision between the sheet and die is balanced by
      the pressure provided by the rubber; the sheet is always under tensile stress
      state due to the friction force provided by rubber; the remaining kinetic energy
      of sheet after collision with the die is absorbed by rubber. Therefore, the
      rebound effect in indirect EMF is suppressed compared with direct EMF. So, the
      fittability of the workpiece is improved, which results in a better forming
      quality.

PMID- 30115857
TI  - Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle
      Chronometabolism.
AB  - Antibiotics lead to increased susceptibility to colonization by pathogenic
      organisms, with different effects on the host-microbiota relationship. Here, we
      show that metronidazole treatment of specific pathogen-free (SPF) mice results in
      a significant increase of the bacterial phylum Proteobacteria in fecal pellets.
      Furthermore, metronidazole in SPF mice decreases hind limb muscle weight and
      results in smaller fibers in the tibialis anterior muscle. In the gastrocnemius
      muscle, metronidazole causes upregulation of Hdac4, myogenin, MuRF1, and
      atrogin1, which are implicated in skeletal muscle neurogenic atrophy.
      Metronidazole in SPF mice also upregulates skeletal muscle FoxO3, described as
      involved in apoptosis and muscle regeneration. Of note, alteration of the gut
      microbiota results in increased expression of the muscle core clock and effector
      genes Cry2, Ror-beta, and E4BP4. PPARgamma and one of its important target genes,
      adiponectin, are also upregulated by metronidazole. Metronidazole in germ-free
      (GF) mice increases the expression of other core clock genes, such as Bmal1 and
      Per2, as well as the metabolic regulators FoxO1 and Pdk4, suggesting a microbiota
      independent pharmacologic effect. In conclusion, metronidazole in SPF mice
      results in skeletal muscle atrophy and changes the expression of genes involved
      in the muscle peripheral circadian rhythm machinery and metabolic regulation.

PMID- 30115860
TI  - PLC-Integrated Sensing Technology in Mountain Regions for Drone Landing Sites:
      Focusing on Software Technology.
AB  - In the Republic of Korea, one of the most widely discussed subjects related to
      future logistics technology is the drone-based delivery (transportation) system.
      Much (around 75%) of Korea's territory consists of mountainous areas; however,
      the costs of installing internet facilities for drone landing sites are very high
      compared to other countries. Therefore, this paper proposes the power-line
      communication (PLC) system introduced in the author's previous study as an
      alternative solution. For the system design, a number of lightning rods are used
      together with a monitoring system. The system algorithm performs substantial data
      analysis. Also, as the author found that instantaneous high-voltage currents were
      a major cause of fire incidents, a three-phase three-wire connection was used for
      the installation of the lightning rods (Bipolar Conventional Air Terminal). Thus,
      based on the PLC technology, an artificial intelligence (AI) which avoids
      lightning strikes at the drone landing site by interworking with a closed-circuit
      television (CCTV) monitoring system when a drone flies over the mountain regions
      is proposed in this paper. The algorithm was implemented with C++ and Unity/C#,
      whereas the application for the part concerning the integrated sensing was
      developed with Java Android.

PMID- 30115856
TI  - Muscle and Bone Health in Postmenopausal Women: Role of Protein and Vitamin D
      Supplementation Combined with Exercise Training.
AB  - Menopause is an age-dependent physiological condition associated with a natural
      decline in oestrogen levels, which causes a progressive decrease of muscle mass
      and strength and bone density. Sarcopenia and osteoporosis often coexist in
      elderly people, with a prevalence of the latter in elderly women. The profound
      interaction between muscle and bone induces a negative resonance between the two
      tissues affected by these disorders worsening the quality of life in the
      postmenopausal period. It has been estimated that at least 1 in 3 women over age
      50 will experience osteoporotic fractures, often requiring hospitalisation and
      long-term care, causing a large financial burden to health insurance systems.
      Hormonal replacement therapy is effective in osteoporosis prevention, but
      concerns have been raised with regard to its safety. On the whole, the increase
      in life expectancy for postmenopausal women along with the need to improve their
      quality of life makes it necessary to develop specific and safe therapeutic
      strategies, alternative to hormonal replacement therapy, targeting both
      sarcopenia and osteoporosis progression. This review will examine the rationale
      and the effects of dietary protein, vitamin D and calcium supplementation
      combined with a specifically-designed exercise training prescription as a
      strategy to counteract these postmenopausal-associated disorders.

PMID- 30115861
TI  - The Effect of Plasma Pretreatment and Cross-Linking Degree on the Physical and
      Antimicrobial Properties of Nisin-Coated PVA Films.
AB  - Stable antimicrobial nisin layers were prepared on the carrying medium-polyvinyl
      alcohol (PVA) films, crosslinked by glutaric acid. Surface plasma dielectric
      coplanar surface barrier discharge (DCSBD) modification of polyvinyl alcohol was
      used to improve the hydrophilic properties and to provide better adhesion of
      biologically active peptide-nisin to the polymer. The surface modification of
      films was studied in correlation to their cross-linking degree. Nisin was
      attached directly from the salt solution of the commercial product. In order to
      achieve a stable layer, the initial nisin concentration and the following release
      were investigated using chromatographic methods. The uniformity and stability of
      the layers was evaluated by means of zeta potential measurements, and for the
      surface changes of hydrophilic character, the water contact angle measurements
      were provided. The nisin long-term stability on the PVA films was confirmed by
      tricine polyacrylamide gel electrophoresis (SDS-PAGE) and by antimicrobial assay.
      It was found that PVA can serve as a suitable carrying medium for nisin with
      tunable properties by plasma treatment and crosslinking degree.

PMID- 30115859
TI  - Potential Therapeutic Agents for Feline Calicivirus Infection.
AB  - Feline calicivirus (FCV) is a major cause of upper respiratory tract disease in
      cats, with widespread distribution in the feline population. Recently, virulent
      systemic diseases caused by FCV infection has been associated with mortality
      rates up to 50%. Currently, there are no direct-acting antivirals approved for
      the treatment of FCV infection. Here, we tested 15 compounds from different
      antiviral classes against FCV using in vitro protein and cell culture assays.
      After the expression of FCV protease-polymerase protein, we established two in
      vitro assays to assess the inhibitory activity of compounds directly against the
      FCV protease or polymerase. Using this recombinant enzyme, we identified
      quercetagetin and PPNDS as inhibitors of FCV polymerase activity (IC50 values of
      2.8 MUM and 2.7 MUM, respectively). We also demonstrate the inhibition of FCV
      protease activity by GC376 (IC50 of 18 uM). Using cell culture assays, PPNDS,
      quercetagetin and GC376 did not display antivirals effects, however, we
      identified nitazoxanide and 2'-C-methylcytidine (2CMC) as potent inhibitors of
      FCV replication, with EC50 values in the low micromolar range (0.6 MUM and 2.5
      MUM, respectively). In conclusion, we established two in vitro assays that will
      accelerate the research for FCV antivirals and can be used for the high
      throughput screening of direct-acting antivirals.

PMID- 30115862
TI  - Cognitive Functioning of Geriatric Patients: Is Hypovitaminosis D the Next Marker
      of Cognitive Dysfunction and Dementia?
AB  - The study objective is to investigate whether vitamin D is associated with the
      cognitive function of geriatric patients. This cross-sectional study involved 357
      patients hospitalized in the geriatric ward who complained of memory problems
      (mean age: 82.3 years). The level of cognitive function was measured with the
      Mini-Mental State Examination (MMSE) and the clinical diagnosis of dementia was
      established according to the International Classification of Diseases (ICD-10)
      criteria. The serum 25-hydroxy vitamin D was measured with liquid chromatography
      tandem mass spectrometry. The iterative Bayesian model averaging (BMA) procedure
      was applied to linear and logistic regression models in order to identify the
      best set of factors describing cognitive dysfunction and dementia, respectively.
      According to BMA, there is strong evidence that higher vitamin D levels, higher
      body mass index (BMI), and higher mobility function measured with the Timed Up
      and Go (TUG) test are independently associated with better cognitive performance
      and lower risk of dementia. Additionally, there is strong evidence that fewer
      years of education and lower vitamin B12 plasma levels independently describe
      worse cognitive performance. However, vitamin B12 levels higher than 800 pg/mL is
      negatively associated with the MMSE performance. Hypovitaminosis D in geriatric
      patients is an underrated marker of cognitive dysfunction and dementia.

PMID- 30115863
TI  - Mitochondrial DNA Haplogroup JT is Related to Impaired Glycaemic Control and
      Renal Function in Type 2 Diabetic Patients.
AB  - The association between mitochondrial DNA (mtDNA) haplogroup and risk of type 2
      diabetes (T2D) is undetermined and controversial. This study aims to evaluate the
      impact of the main mtDNA haplogroups on glycaemic control and renal function in a
      Spanish population of 303 T2D patients and 153 healthy controls. Anthropometrical
      and metabolic parameters were assessed and mtDNA haplogroup was determined in
      each individual. Distribution of the different haplogroups was similar in
      diabetic and healthy populations and, as expected, T2D patients showed poorer
      glycaemic control and renal function than controls. T2D patients belonging to the
      JT haplogroup (polymorphism m.4216T>C) displayed statistically significant higher
      levels of fasting glucose and HbA1c than those of the other haplogroups,
      suggesting a poorer glycaemic control. Furthermore, diabetic patients with the JT
      haplogroup showed a worse kidney function than those with other haplogroups,
      evident by higher levels of serum creatinine, lower estimated glomerular
      filtration rate (eGFR), and slightly higher (although not statistically
      significant) urinary albumin-to-creatinine ratio. Our results suggest that JT
      haplogroup (in particular, change at position 4216 of the mtDNA) is associated
      with poorer glycaemic control in T2D, which can trigger the development of
      diabetic nephropathy.

PMID- 30115865
TI  - Electro-Conductive Composite Gold-Polyethersulfone-Ultrafiltration-Membrane:
      Characterization of Membrane and Natural Organic Matter (NOM) Filtration
      Performance at Different In-Situ Applied Surface Potentials.
AB  - Next to the pore size distribution, surface charge is considered to be one main
      factor in the separation performance of ultrafiltration (UF) membranes. By
      applying an external surface potential onto an electro-conductive UF membrane,
      electrostatic induced rejection was investigated. This study introduces in a
      first part a relatively simple but yet not reported technology of membrane
      modification with direct current sputter deposition of ultrathin (15 nm) highly
      conductive gold layers. In a second part, characterization of the gold-coated UF
      flat sheet membrane with a molecular weight cut-off (MWCO) of 150 kDa is
      presented. Membrane parameters as contact angle (hydrophobicity), pure water
      permeability, MWCO, scanning electron microscopy imaging, zeta potential, surface
      conductivity and cyclic voltammetry of the virgin and the modified membrane are
      compared. Due to the coating, a high surface conductivity of 107 S m-1 was
      realized. Permeability of the modified membrane decreased by 40% but MWCO and
      contact angle remained almost unchanged. In a third part, cross-flow filtration
      experiments with negative charged Suwannee River Natural Organic Matter (SRNOM)
      are conducted at different cathodic and anodic applied potentials, different pH
      values (pH 4, 7, 10) and ionic strengths (0, 1, 10 mmol L-1). SRNOM rejection of
      not externally charged membrane was 28% in cross-flow and 5% in dead-end mode.
      Externally negative charged membrane (-1.5 V vs. Ag/AgCl) reached rejection of
      64% which was close to the performance of commercial UF membrane with MWCO of 5
      kDa. High ionic strengths or low pH of feed reduced the effect of electrostatic
      rejection.

PMID- 30115864
TI  - Vitamin D and Influenza-Prevention or Therapy?
AB  - Vitamin D generates many extraskeletal effects due to the vitamin D receptor
      (VDR) which is present in most tissues throughout the body. The possible role of
      vitamin D in infections is implied from its impact on the innate and adaptive
      immune responses. A significant effect is also the suppression of inflammatory
      processes. Because vitamin D could be acknowledged as a "seasonal stimulus", as
      defined by R. Edgar Hope-Simpson, it would be crucial to prove it from a
      potential easy and cheap prophylaxis or therapy support perspective as far as
      influenza infections are concerned. The survey of the literature data generates
      some controversies and doubts about the possible role of vitamin D in the
      prevention of influenza virus. The most important point is to realise that the
      broad spectrum of this vitamin's activity does not exclude such a possibility.
      According to most of the authors, more randomized controlled trials with
      effective, large populations are needed to explore the preventive effect of
      vitamin D supplementation on viral influenza infections.

PMID- 30115867
TI  - Graphene Quantum Dots Decorated Al-doped ZnS for Improved Photoelectric
      Performance.
AB  - Graphene quantum dots (GQDs) decorated Al-doped ZnS composites were prepared
      using the solvothermal process, and the hydrothermal method was used to prepare
      GQDs. Various spectroscopic techniques were used to characterize the products,
      and the results show that Al-ZnS attached GQD composites present lattice fringes
      that can be assigned to ZnS and GQDs, respectively. The absorption peaks of Al
      ZnS/GQDs are red-shifted because of the doping of aluminum and the incorporation
      of GQDs. The luminescence intensity of Al-ZnS/GQDs shows a downward trend with
      the addition of GQDs. As the GQD content changes from 0.6 wt % to 1.8 wt %, the
      photocurrent density achieves a maximum at the addition of 1.2 wt %. The
      photocurrent of Al-ZnS/GQDs composites are about 700% and 200% of pure ZnS and Al
      ZnS, respectively. The results indicate that Al doping can reduce the energy
      bandgap of ZnS and produce more photogenerated electrons. The photogenerated
      electrons from Al-ZnS can be extracted and transferred to GQDs, which act as
      conducting materials to decrease the recombination rate and improve the
      photogenerated electron-transfer.

PMID- 30115866
TI  - Genome-Wide Quantification of the Effect of Gene Overexpression on Escherichia
      coli Growth.
AB  - Recombinant protein production plays an essential role in both biological studies
      and pharmaceutical production. Escherichia coli is one of the most favorable
      hosts for this purpose. Although a number of strategies for optimizing protein
      production have been developed, the effect of gene overexpression on host cell
      growth has been much less studied. Here, we performed high-throughput tests on
      the E. coli a complete set of E. coli K-12 ORF archive (ASKA) collection to
      quantify the effects of overexpressing individual E. coli genes on its growth.
      The results indicated that overexpressing membrane-associated proteins or
      proteins with high abundances of branched-chain amino acids tended to impair cell
      growth, the latter of which could be remedied by amino acid supplementation.
      Through this study, we expect to provide an index for a fast pre-study estimate
      of host cell growth in order to choose proper rescuing approaches when working
      with different proteins.

PMID- 30115868
TI  - Modification of the AFM Sensor by a Precisely Regulated Air Stream to Increase
      Imaging Speed and Accuracy in the Contact Mode.
AB  - Increasing the imaging rate of atomic force microscopy (AFM) without impairing of
      the imaging quality is a challenging task, since the increase in the scanning
      speed leads to a number of artifacts related to the limited mechanical bandwidth
      of the AFM components. One of these artifacts is the loss of contact between the
      probe tip and the sample. We propose to apply an additional nonlinear force on
      the upper surface of a cantilever, which will help to keep the tip and surface in
      contact. In practice, this force can be produced by the precisely regulated
      airflow. Such an improvement affects the AFM system dynamics, which were
      evaluated using a mathematical model that is presented in this paper. The model
      defines the relationships between the additional nonlinear force, the pressure of
      the applied air stream, and the initial air gap between the upper surface of the
      cantilever and the end of the air duct. It was found that the nonlinear force
      created by the stream of compressed air (aerodynamic force) prevents the contact
      loss caused by the high scanning speed or the higher surface roughness, thus
      maintaining stable contact between the probe and the surface. This improvement
      allows us to effectively increase the scanning speed by at least 10 times using a
      soft (spring constant of 0.2 N/m) cantilever by applying the air pressure of 40
      Pa. If a stiff cantilever (spring constant of 40 N/m) is used, the potential of
      vertical deviation improvement is twice is large. This method is suitable for use
      with different types of AFM sensors and it can be implemented practically without
      essential changes in AFM sensor design.

PMID- 30115870
TI  - Analysis of Water, Ethanol, and Fructose Mixtures Using Nondestructive Resonant
      Spectroscopy of Mechanical Vibrations and a Grouping Genetic Algorithm.
AB  - A new haptic sensor that is based on vibration produced by mechanical excitation
      from a clock coupled to a resonant cavity is presented. This sensor is intended
      to determine the chemical composition of liquid mixtures in a completely non
      destructive method. In this case, a set of 23 samples of water, ethanol, and
      fructose mixtures has been used to simulate different kinds of alcoholic
      beverage. The spectral information from the vibrational absorption bands of
      liquid samples is analyzed by a Grouping Genetic Algorithm. An Extreme Learning
      Machine implements the fitness function that is able to classify the mixtures
      according to the concentration of ethanol and fructose. The 23 samples range from
      0%-13% by volume of ethanol and from 0-3 g/L of fructose, all of them with
      different concentration. The new technique achieves an average classification
      accuracy of 96%.

PMID- 30115869
TI  - Eutypellenoids A-C, New Pimarane Diterpenes from the Arctic Fungus Eutypella sp.
      D-1.
AB  - Three new pimarane diterpenes, eutypellenoids A-C (1-3), together with a known
      compound, eutypenoid C (4), were isolated from the culture extract of Eutypella
      sp. D-1 derived from the Arctic region. Compounds 1-3 possessed an uncommon
      tetrahydrofuran-fused pimarane diterpene skeleton. The structures of all
      compounds were determined by detailed spectroscopic analysis, electronic circular
      dichroism (ECD) analysis, as well as a comparison with the literature data.
      Antibacterial, antifungal, and cytotoxic activities of these compounds were
      evaluated. Compound 2 displayed antibacterial activity against Staphylococcus
      aureus and Escherichia coli with MIC values of 8 and 8 MUg/mL, respectively.
      Additionally, compound 2 showed antifungal activity against Candidaparapsilosis,
      Candida albicans, Candida glabrata, and Candida tropicalis with MIC values of 8,
      8, 16, and 32 MUg/mL, respectively. Furthermore, compound 2 exhibited moderate
      cytotoxic activity against HCT-116 cell line with IC50 value of 3.7 MUM.

PMID- 30115871
TI  - Comparative Computational and Experimental Detection of Adenosine Using
      Ultrasensitive Surface-Enhanced Raman Spectroscopy.
AB  - To better understand detection and monitoring of the important neurotransmitter
      adenosine at physiological levels, this study combines quantum chemical density
      functional modeling and ultrasensitive surface-enhanced Raman spectroscopic
      (SERS) measurements. Combined simulation results and experimental data for an
      analyte concentration of about 10-11 molar indicate the presence of all known
      molecular forms resulting from adenosine's complex redox-reaction. Detailed
      analysis presented here, besides assessing potential Raman signatures of these
      adenosinic forms, also sheds light on the analytic redox process and voltammetric
      detection. Examples of adenosine Raman fingerprints for different molecular
      orientations with respect to the SERS substrate are the vibrational line around
      920 +/- 10 cm-1 for analyte physisorption through the carbinol moiety and around
      1600 +/- 20 cm-1 for its fully oxidized form. However, both hydroxyl/oxygen sites
      and NH2/nitrogen sites contribute to molecule's interaction with the SERS
      environment. Our results also reveal that contributions of partially oxidized
      adenosine forms and of the standard form are more likely to be detected with the
      first recorded voltammetric oxidation peak. The fully oxidized adenosine form
      contributes mostly to the second peak. Thus, this comparative theoretical
      experimental investigation of adenosine's vibrational signatures provides
      significant insights for advancing its detection, and for future development of
      opto-voltammetric biosensors.

PMID- 30115872
TI  - Intrathecal Injection of Dual Zipper Kinase shRNA Alleviating the Neuropathic
      Pain in a Chronic Constrictive Nerve Injury Model.
AB  - Dual leucine zipper kinase (DLK) is a member of mitogen-activated protein kinase
      kinase kinase (MAP3K) family mainly involved in neuronal degeneration. However,
      the role of DLK signaling in the neuropathic pain has not yet been fully
      determined. Chronic constrictive injury (CCI) was conducted by four 3-0 chromic
      gut ligatures loosely ligated around the sciatic nerve. Escalated DLK expression
      over the dorsal root ganglion was observed from one to four rings of CCI.
      Remarkable expression of DLK was observed in primary dorsal root ganglion cells
      culture subjected to electrical stimulation and attenuated by DLK short hairpin
      RNA (shRNA) treatment. Intrathecal injection of DLK shRNA attenuates the
      expression of DLK over the dorsal root ganglion and hippocampus neurons and
      increased the threshold of mechanical allodynia and decreased thermal
      hyperalgesia. In CatWalk gait analysis, significant decreases of print area,
      maximum contact maximum intensity, stand phase, single stance, and regular index
      by CCI were alleviated by the DLK shRNA administration. In conclusion, the
      expression of DLK was up-regulated in chronic constrictive injury and attenuated
      by the administration of DLK shRNA, which paralleled the improvement of
      neurobehavior of neuropathic pain. The modulation of DLK expression is a
      potential clinic treatment option for neuropathic pain.

PMID- 30115873
TI  - A Simple Mannose-Coated Poly (p-Phenylene Ethynylene) for Qualitative Bacterial
      Capturing.
AB  - A mannose-functionalized poly (p-phenylene ethynylene) was rationally designed to
      achieve selective detection of bacteria. The polymer was constructed as a
      signaling unit and was modified by attaching aminoethyl mannose using the
      carboxylic acid group at the end of the linker. Incubation of Escherichiacoli
      with the polymer yielded fluorescent bacteria aggregates through polyvalent
      interactions. The utility of the mannose functionalized polymer to detect E.coli
      expressing functional FimH mannose-specific lectin on their surface was also
      demonstrated. The sugar units displayed on the surface of the polymer retained
      their functional ability to interact with mannose-binding lectin. To determine
      the optimum binding time, we measured the fluorescence intensity of the polymer
      bacteria suspension at intervals. Our results showed that binding in this system
      will reach an optimum level within 30 min of incubation. The polymer's affinity
      for bacteria has been demonstrated and bacteria with a concentration of 103 CFU
      mL-1 can be detected by this system.

PMID- 30115875
TI  - The Effect of Alkyl Chain Number in Sucrose Surfactant on the Physical Properties
      of Quercetin-Loaded Deformable Nanoliposome and Its Effect on In Vitro Human Skin
      Penetration.
AB  - Non-invasive skin penetration of a drug is increased by an edge activator, which
      enhances the nanoliposome deformability. The objective of this study was to
      investigate the role of the alkyl chain number of sucrose surfactants as an edge
      activator in elastic nanoliposomes. In addition, the physicochemical properties
      of the elastic nanoliposomes were characterized and an in vitro human skin
      permeation study was performed. Elastic nanoliposomes that were composed of
      sucrose monostearate (MELQ), sucrose distearate (DELQ), and sucrose tristearte
      (TELQ) were prepared using a thin-film hydration method. Particle size and
      entrapment efficiency of elastic nanoliposomes increased proportionally with an
      increase in the amounts and the numbers of the stearate in sucrose surfactant.
      Deformability of elastic nanoliposomes was indicated as DELQ > MELQ > TELQ and
      the same pattern was revealed through the in vitro human skin permeability tests.
      These results suggest that the number of alkyl chains of sucrose surfactant as
      edge activator affects the physicochemical property, stability, and skin
      permeability in elastic nanoliposome. Our findings give a valuable platform for
      the development of elastic nanoliposomes as skin drug delivery systems.

PMID- 30115874
TI  - Enhancement of Radiation Effectiveness in Cervical Cancer Cells by Combining
      Ionizing Radiation with Hyperthermia and Molecular Targeting Agents.
AB  - Hyperthermia (HT) and molecular targeting agents can be used to enhance the
      effect of radiotherapy (RT). The purpose of this paper is to evaluate radiation
      sensitization by HT and different molecular targeting agents (Poly [ADP-ribose]
      polymerase 1 inhibitor, PARP1-i; DNA-dependent protein kinase catalytic subunit
      inhibitor, DNA-PKcs-i and Heat Shock Protein 90 inhibitor, HSP90-i) in cervical
      cancer cell lines. Survival curves of SiHa and HeLa cells, concerning the
      combined effects of radiation with hyperthermia and PARP1-i, DNA-PKcs-i or HSP90
      i, were analyzed using the linear-quadratic model: S(D)/S(0) = exp - (alphaD +
      betaD2). The values of the linear-quadratic (LQ) parameters alpha and beta,
      determine the effectiveness at low and high doses, respectively. The effects of
      these sensitizing agents on the LQ parameters are compared to evaluate dose
      dependent differences in radio enhancement. Combination of radiation with
      hyperthermia, PARP1-i and DNA-PKcs-i significantly increased the value of the
      linear parameter alpha. Both alpha and beta were significantly increased for
      HSP90-i combined with hyperthermia in HeLa cells, though not in SiHa cells. The
      Homologous Recombination pathway is inhibited by hyperthermia. When hyperthermia
      is combined with DNA-PKcs-i and PARP1-i, the Non-Homologous End Joining or
      Alternative Non-Homologous End Joining pathway is also inhibited, leading to a
      more potent radio enhancement. The observed increments of the alpha value imply
      that significant radio enhancement is obtained at clinically-used radiotherapy
      doses. Furthermore, the sensitizing effects of hyperthermia can be even further
      enhanced when combined with other molecular targeting agents.

PMID- 30115877
TI  - Fabrication of Cu Based Metallic Binder for Diamond Tools by Microwave
      Pressureless Sintering.
AB  - Microwave pressureless sintering (MPS) method is successfully applied in the
      fabrication of Cu based metallic matrix for diamond tools. The main purpose of
      this work is to obtain better mechanical properties when the metal binder of the
      diamond tools was prepared by the MPS method. The orthogonal experimental method
      is adopted to design the sintering process parameters. The optimized experimental
      conditions are suggested as 880  degrees C of sintering temperature, 375 MPa of
      cold pressure, and 35 min of withholding time. The contrastive investigation of
      the MPS and conventional pressureless sintering (CPS) are performed under
      optimized conditions. The microstructures information are obtained by scanning
      electron microscopy (SEM), X-ray diffraction (XRD), electron probe microanalysis
      (EPMA), and the necessary mechanical properties, such as relative density,
      hardness, and flexural strength are tested. Experimental results show that the
      MPS method, compared with CPS, can significantly improve the mechanical
      properties of the metallic matrix. The factors of relative density, hardness, and
      flexural strength increase 1.25%, 3.86%, and 6.28%, respectively. The possible
      sintering mechanism of the MPS method is also discussed. This work may provide a
      reference for the fabrication of metal-based diamond tools by microwave heating
      method.

PMID- 30115878
TI  - Mechanical Properties Study of Fe-Mn-Si Shape Memory Alloys Welding Seam Formed
      by Laser Welding with Filler Powder.
AB  - To reduce the residual stress and improve the fatigue property of the laser
      weldment by using the stress self-accommodation characteristic of Fe-Mn-Si shape
      memory alloys (SMAs), a Fe15Mn5Si12Cr6Ni memory alloy welding seam was formed
      inside 304 stainless steel by laser welding with filler powder. The combination
      of the hole-drilling method and the ANSYS software was used to research the
      distribution law of residual stress inside the laser welding specimen. The
      fatigue strength of the laser welded specimens with the Fe-Mn-Si SMAs welding
      seam (experimental materials) and 304 stainless steel welding seam (comparative
      materials) was measured by cycle bending fatigue test. The microhardness of the
      welding specimens was measured by the microhardness tester. The thermodynamic
      model of the laser welding process and the phase transition crystallography of Fe
      Mn-Si SMAs were evaluated to analyze the strengthening mechanism of the
      mechanical properties in the experimental materials. The results show that the
      distribution law for residual stress in the experiment and simulation are
      consistent. The experimental materials possess low residual stress, high fatigue
      strength and high microhardness. The strengthening mechanism for mechanical
      properties is the welding residual stress-induced gamma->epsilon martensitic
      transformation inside the experimental materials, which causes the tensile
      plastic strain of the welding seam to resist residual compression strain, and the
      residual stress, as the transition driving force, is released in shear
      processing.

PMID- 30115876
TI  - Hepatoprotective Effects of MHY3200 on High-Fat, Diet-Induced, Non-Alcoholic
      Fatty Liver Disease in Rats.
AB  - This study investigated the effects of 2-(4-(5-chlorobenzo[d]thiazol-2
      yl)phenoxy)-2,2-difluoroacetic acid (MHY3200) on high-fat diet (HFD)-induced
      hepatic lipid accumulation and inflammation. The measurement of peroxisome
      proliferator-activated receptor (PPAR)alpha activity by using a luciferase assay
      indicated that MHY3200 was more potent than a known PPARalpha agonist, WY14643,
      in AC2F cells. Six-month-old male SD rats were fed chow or HFD for 1 month, and
      after, with or without added MHY3200 (1 or 2 mg/kg/day) for 4 weeks. The oral
      administration of MHY3200 caused a significant decrease in serum triglyceride
      (TG), glucose, alanine aminotransferase, and insulin, as well as a slight
      decrease in the level of free fatty acid and aspartate transaminase. No weight
      gain was detected when compared with HFD rats, and hepatic TG content was also
      attenuated by the administration of MHY3200. Furthermore, phosphorylation of the
      ER stress marker, inositol-requiring kinase 1 and its downstream gene, c-Jun N
      terminal kinase, in addition to serine phosphorylation of insulin receptor
      substrate 1 were suppressed by MHY3200. Consistent with these results, MHY3200
      administration reduced the levels of activation of protein-1, cyclooxygenase-2,
      and inducible nitric oxide synthase. Our results suggested that MHY3200
      ameliorated HFD-induced hepatic lipid accumulation and inflammation, and improved
      insulin resistance through PPARalpha activation.

PMID- 30115879
TI  - Effects of Different Doses of Fructooligosaccharides (FOS) on the Composition of
      Mice Fecal Microbiota, Especially the Bifidobacterium Composition.
AB  - Fructooligosaccharides (FOS) are a well-known class of prebiotic and are
      considered to selectively stimulate the growth of bifidobacteria in the gut.
      Previous studies focused on the growth stimulation of Bifidobacterium, but they
      did not further investigate the bifidobacterial composition and the specific
      species that were stimulated. In this study, mice were fed with FOS in different
      doses for four weeks and the composition of fecal microbiota, in particular
      Bifidobacterium, was analyzed by sequencing the V3-V4 region and the groEL gene
      on the MiSeq platform, respectively. In the high-dose group, the relative
      abundance of Actinobacteria was significantly increased, which was mainly
      contributed by Bifidobacterium. At the genus level, the relative abundances of
      Blautia and Coprococcus were also significantly increased. Through the groEL
      sequencing, 14 species of Bifidobacterium were identified, among which
      B.pseudolongum was most abundant. After FOS treatment, B.pseudolongum became
      almost the sole bifidobacterial species (>95%). B.pseudolongum strains were
      isolated and demonstrated their ability to metabolize FOS by high performance
      liquid chromatography (HPLC). Therefore, we inferred that FOS significantly
      stimulated the growth of B.pseudolongum in mice. Further investigations are
      needed to reveal the mechanism of selectiveness between FOS and B.pseudolongum,
      which would aid our understanding of the basic principles between dietary
      carbohydrates and host health.

PMID- 30115881
TI  - Polyamine Biosynthetic Pathway as a Drug Target for Osteosarcoma Therapy.
AB  - Osteosarcoma (OS) is the most common bone tumor in children. Polyamines (PAs) are
      ubiquitous cations involved in many cell processes including tumor development,
      invasion and metastasis. In other pediatric cancer models, inhibition of the PA
      biosynthesis pathway with ornithine decarboxylase (ODC) inhibitor alpha
      difluoromethylornithine (DFMO) results in decreased cell proliferation and
      differentiation. In OS, the PA pathway has not been evaluated. DFMO is an
      attractive, orally administered drug, is well tolerated, can be given for
      prolonged periods, and is already used in pediatric patients. Three OS cell lines
      were used to study the cellular effects of PA inhibition with DFMO: MG-63, U-2 OS
      and Saos-2. Effects on proliferation were analyzed by cell count, flow cytometry
      based cell cycle analysis and RealTime-GloTM MT Cell Viability assays.
      Intracellular PA levels were measured with high-performance liquid chromatography
      (HPLC). Western blot analysis was used to evaluate cell differentiation. DFMO
      exposure resulted in significantly decreased cell proliferation in all cell
      lines. After treatment, intracellular spermidine levels were drastically
      decreased. Cell cycle arrest at G2/M was observed in U-2 OS and Saos-2. Cell
      differentiation was most prominent in MG-63 and U-2 OS as determined by increases
      in the terminal differentiation markers osteopontin and collagen 1a1. Cell
      proliferation continued to be suppressed for several days after removal of DFMO.
      Based on our findings, DFMO is a promising new adjunct to current osteosarcoma
      therapy in patients at high risk of relapse, such as those with poor necrosis at
      resection or those with metastatic or recurrent osteosarcoma. It is a well
      tolerated oral drug that is currently in phase II clinical trials in pediatric
      neuroblastoma patients as a maintenance therapy. The same type of regimen may
      also improve outcomes in osteosarcoma patients in whom there have been
      essentially no medical advances in the last 30 years.

PMID- 30115880
TI  - An Audit of Australian Bread with a Focus on Loaf Breads and Whole Grain.
AB  - Bread is a vehicle for a range of nutrients within the Australian diet, but has
      been the target of negative press. The aim of this study was to examine bread
      products, particularly white, whole grain and gluten-free loaves, including
      nutrients, health claims and Health Star Rating (HSR). An audit of four
      supermarkets and a bakery franchise (2017) was compared with 2014 data. Median
      and range was calculated for whole grain content, dietary fibre, sodium, protein,
      carbohydrate and sugar. Of all breads (n = 456), 29% were eligible to make a
      whole grain claim with 27% very high in whole grain (>=24 g/serve), an 18%
      increase from 2014. Within loaves (n = 243), 40% were at least a source of whole
      grain (>=8 g/serve), 79% were at least a source of dietary fibre, 54% met the
      sodium reformulation target (<=400 mg/100 g), 78% were a 'source' and 20% were a
      'good source' of protein (10 g/serve), and 97% were low in sugar. Despite
      significant differences between loaves for all nutrients assessed, HSR did not
      differ between white and whole grain varieties. Compared to 2014, there were 20
      fewer white loaves and 20 additional whole grain loaves which may assist more
      Australians achieve the 48g whole grain daily target intake.

PMID- 30115882
TI  - Moderators of School-Based Physical Activity Interventions on Cardiorespiratory
      Endurance in Primary School-Aged Children: A Meta-Regression.
AB  - The purpose of this study was to examine potential moderators of school-based
      physical activity interventions on cardiorespiratory endurance in primary school
      aged children using meta-regression. An Internet search with several databases
      was employed, extracting school-based pediatric physical activity intervention
      studies published within the past 30 years. Studies were included if there was a
      control or comparison group, if the study sample included primary school-aged
      children, if the targeted outcome of cardiorespiratory endurance was objectively
      assessed, if the intervention was at least partially school-based, and if the
      effect estimate's variability was reported. An inverse-variance random effects
      meta-regression was employed using the primary predictors of component number
      (single component or multi-component) and intervention length using 20 extracted
      studies with 23 total effects. The overall pooled effect on cardiorespiratory
      endurance was statistically significant (Hedges' g = 0.30, 95% C.I.: 0.19-0.40; p
      < 0.001). Using random effects meta-regression, neither component number (b = 
      0.09, 95% C.I.: -0.40-0.23; p = 0.560) or intervention length (b = 0.001, 95%
      C.I.: -0.002-0.004; p = 0.427) yielded a significant modifying effect on
      cardiorespiratory endurance. School-based physical activity interventions have a
      significant pooled effect on cardiorespiratory endurance in primary school-aged
      children. Component number and intervention length does not modify this effect,
      suggesting other sources for between-study heterogeneity.

PMID- 30115883
TI  - Prenylated Flavonoids from Roots of Glycyrrhiza uralensis Induce Differentiation
      of B16-F10 Melanoma Cells.
AB  - Roots of Glycyrrhiza uralensis have been used as herbal medicine and natural
      sweetener. By activity-guided phytochemical investigation of the extracts from
      G.uralensis root, ten flavonoids, namely GF-1-GF-10, of which five were
      prenylated flavonoids, were found to show antiproliferative effects in melanoma
      B16-F10 cells. Three of the prenylated flavonoids, namely GF-1, GF-4 and GF-9,
      significantly induced the differentiation of B16-F10 cells; the inductions
      included increase of tyrosinase activity, tyrosinase protein, and melanin
      content. In GF-1 and GF-9 induced melanoma differentiation, the phosphorylation
      of p38 MAPK (mitogen activated potein kinase) was identified; while GF-4 could
      trigger the phosphorylation of PI3K/AKT (phosphatidylinositol 3-kinase/Protein
      Kinase B) signaling. However, application of GF-6 to the melanoma cells did not
      induce differentiation; but which promoted cell apoptotic signaling, i.e.,
      increase levels of cleaved-PRAP, cleaved-caspase 3, and cleaved-caspase 9. These
      results suggested that different types of prenylated flavonoids from G.uralensis
      might have potential anticancer effects against melanoma cells by acting through
      different signaling pathways.

PMID- 30115885
TI  - Methylmercury in Industrial Harbor Sediments in Taiwan: First Observations on its
      Occurrence, Distribution, and Measurement.
AB  - The distribution of methylmercury (MeHg) and total mercury (T-Hg) in sediments of
      the estuaries and the basin in Kaohsiung Harbor (Taiwan) is studied. MeHg in the
      sediment samples was determined using gas chromatography-mass spectrometry. The
      certified reference material of sediments with respect to the method showed the
      recovery efficiency between 97.4 and 103.6% which confirmed the applicability of
      analysis method. The T-Hg and MeHg concentrations were between 149 to 9035 MUg/kg
      and <0.31 to 17.7 MUg/kg, respectively. The T-Hg and MeHg concentrations in the
      estuaries of Kaohsiung Harbor were relatively high. Results suggest that Hg in
      this studied area was likely contributed from the catchments of the rivers. The
      MeHg level was <0.01 to 2.66% of the T-Hg in the sediments. A positive
      correlation is obtained between MeHg, T-Hg, and total organic carbon in the
      sediments, whereas a negative correlation is observed between pH, oxidation
      reduction potential, and MeHg concentration. The results further suggest that
      sediment characteristics contribute mainly to the distribution of MeHg.

PMID- 30115887
TI  - Endotoxins from a Pharmacopoeial Point of View.
AB  - A pyrogen is a substance that causes fever after intravenous administration or
      inhalation. Gram negative endotoxins are the most important pyrogens to
      pharmaceutical laboratories. In the International, United States, Japanese and
      European Pharmacopoeias, there are two official methods to evaluate
      pyrogenicitythat is, the bacterial endotoxin test, and the pyrogen test. The main
      objective of this review is to compare the monographs of each test among the
      different Pharmacopeias, to detect similarities and differences. The former can
      be considered fully harmonized, and only non-significant differences were
      detected. The latter, which is the only available assay for some products and
      formulations to demonstrate apyrogenicity, shows large differences, which should
      be considered.

PMID- 30115884
TI  - Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and
      Beyond.
AB  - Sonic hedgehog (Shh), a member of the hedgehog (Hh) family, was originally
      recognized as a morphogen possessing critical characters for neural development
      during embryogenesis. Recently, however, Shh has emerged as an important
      modulator in adult neural tissues through different mechanisms such as
      neurogenesis, anti-oxidation, anti-inflammation, and autophagy. Therefore, Shh
      may potentially have clinical application in neurodegenerative diseases and brain
      injuries. In this article, we present some examples, including ours, to show
      different aspects of Shh signaling and how Shh agonists or mimetics are used to
      alter the neuronal fates in various disease models, both in vitro and in vivo.
      Other potential mechanisms that are discussed include alteration of mitochondrial
      function and anti-aging effect; both are critical for age-related
      neurodegenerative diseases. A thorough understanding of the protective mechanisms
      elicited by Shh may provide a rationale to design innovative therapeutic regimens
      for various neurodegenerative diseases.

PMID- 30115888
TI  - Colonized Sabethes cyaneus, a Sylvatic New World Mosquito Species, Shows a Low
      Vector Competence for Zika Virus Relative to Aedes aegypti.
AB  - The introduction of Zika virus (ZIKV) to the Americas raised concern that the
      virus would spill back from human transmission, perpetuated by Aedes aegypti,
      into a sylvatic cycle maintained in wildlife and forest-living mosquitoes. In the
      Americas, Sabethes species are vectors of sylvatic yellow fever virus (YFV) and
      are therefore candidate vectors of a sylvatic ZIKV cycle. To test the potential
      of Sabethes cyaneus to transmit ZIKV, Sa. cyaneus and Ae. aegypti were fed on
      A129 mice one or two days post-infection (dpi) with a ZIKV isolate from Mexico.
      Sa. cyaneus were sampled at 3, 4, 5, 7, 14, and 21 days post-feeding (dpf) and
      Ae. aegypti were sampled at 14 and 21 dpf. ZIKV was quantified in mosquito
      bodies, legs, and saliva to measure infection, dissemination, and potential
      transmission, respectively. Of 69 Sa. cyaneus that fed, ZIKV was detected in only
      one, in all body compartments, at 21 dpf. In contrast, at 14 dpf 100% of 20 Ae.
      aegypti that fed on mice at 2 dpi were infected and 70% had virus in saliva.
      These data demonstrate that Sa. cyaneus is a competent vector for ZIKV, albeit
      much less competent than Ae. aegypti.

PMID- 30115886
TI  - Diffuse Gastric Cancer: A Summary of Analogous Contributing Factors for Its
      Molecular Pathogenicity.
AB  - Gastric cancer is the third leading cause of cancer-related deaths and ranks as
      the fifth most common cancer worldwide. Incidence and mortality differ depending
      on the geographical region and gastric cancer ranks first in East Asian
      countries. Although genetic factors, gastric environment, and Helicobacter pylori
      infection have been associated with the pathogenicity and development of
      intestinal-type gastric cancer that follows the Correa's cascade, the
      pathogenicity of diffuse-type gastric cancer remains mostly unknown and
      undefined. However, genetic abnormalities in the cell adherence factors, such as
      E-cadherin and cellular activities that cause impaired cell integrity and
      physiology, have been documented as contributing factors. In recent years, H.
      pylori infection has been also associated with the development of diffuse-type
      gastric cancer. Therefore, in this report, we discuss the host factors as well as
      the bacterial factors that have been reported as associated factors contributing
      to the development of diffuse-type gastric cancer.

PMID- 30115889
TI  - Moderate Effect of Flavonoids on Vascular and Renal Function in Spontaneously
      Hypertensive Rats.
AB  - Many studies have shown that flavonoids are effective as antihypertensive drugs
      in arterial hypertension. In the present work, we have analyzed the effects of
      some flavonoid extracts in the spontaneous hypertensive rat model (SHR). An
      important feature of this study is that we have used a low dose, far from those
      that are usually applied in human therapy or experimental animals, a dose that
      responded to the criterion of a potential future commercial use in human
      subjects. Treatments were carried out for 6 and 12 weeks in two groups of SHR
      rats, which received apigenin, lemon extract, grapefruit + bitter orange (GBO)
      extracts, and cocoa extract. Captopril was used as a positive control in the SHR
      group treated for 6 weeks (SHR6) and Diosmin was used as the industry reference
      in the SHR group treated for 12 weeks (SHR12). Captopril and GBO extracts lowered
      the high arterial pressure of the SHR6 animals, but none of the extracts were
      effective in the SHR12 group. Apigenin, lemon extract (LE), GBO, and captopril
      also improved aortic vascular relaxation and increased plasma and urinary
      excretion of nitrites, but only in the SHR6 group. Kidney and urinary
      thiobarbituric acid reactive substances (TBARS) were also significantly reduced
      by GBO in the SHR6 rats. Apigenin also improved vascular relaxation in the SHR12
      group and all the flavonoids studied reduced urinary thiobarbituric acid reactive
      substances (TBARS) excretion and proteinuria. Vascular abnormalities, such as
      lumen/wall ratio in heart arteries and thoracic aorta, were moderately improved
      by these treatments in the SHR6 group. In conclusion, the flavonoid-rich extracts
      included in this study, especially apigenin, LE and GBO improved vascular
      vasodilatory function of young adult SHRs but only the GBO-treated rats benefited
      from a reduction in blood pressure. These extracts may be used as functional food
      ingredients with a moderate therapeutic benefit, especially in the early phases
      of arterial hypertension.

PMID- 30115890
TI  - Sol-Gel Synthesis of Silicon-Doped Lithium Manganese Oxide with Enhanced
      Reversible Capacity and Cycling Stability.
AB  - A series of silicon-doped lithium manganese oxides were obtained via a sol-gel
      process. XRD characterization results indicate that the silicon-doped samples
      retain the spinel structure of LiMn2O4. Electrochemical tests show that
      introducing silicon ions into the spinel structure can have a great effect on
      reversible capacity and cycling stability. When cycled at 0.5 C, the optimal Si
      doped LiMn2O4 can exhibit a pretty high initial capacity of 140.8 mAh g-1 with
      excellent retention of 91.1% after 100 cycles, which is higher than that of the
      LiMn2O4, LiMn1.975Si0.025O4, and LiMn1.925Si0.075O4 samples. Moreover, the
      optimal Si-doped LiMn2O4 can exhibit 88.3 mAh g-1 with satisfactory cycling
      performance at 10 C. These satisfactory results are mainly contributed by the
      more regular and increased MnO6 octahedra and even size distribution in the
      silicon-doped samples obtained by sol-gel technology.

PMID- 30115891
TI  - Deacetylation of Histone H4 Accompanying Cardiomyogenesis is Weakened in HDAC1
      Depleted ES Cells.
AB  - Cell differentiation into cardiomyocytes requires activation of differentiation
      specific genes and epigenetic factors that contribute to these physiological
      processes. This study is focused on the in vitro differentiation of mouse
      embryonic stem cells (mESCs) induced into cardiomyocytes. The effects of
      clinically promising inhibitors of histone deacetylases (HDACi) on mESC
      cardiomyogenesis and on explanted embryonic hearts were also analyzed. HDAC1
      depletion caused early beating of cardiomyocytes compared with those of the wild
      type (wt) counterpart. Moreover, the adherence of embryonic bodies (EBs) was
      reduced in HDAC1 double knockout (dn) mESCs. The most important finding was
      differentiation-specific H4 deacetylation observed during cardiomyocyte
      differentiation of wt mESCs, while H4 deacetylation was weakened in HDAC1
      depleted cells induced to the cardiac pathway. Analysis of the effect of HDACi
      showed that Trichostatin A (TSA) is a strong hyperacetylating agent, especially
      in wt mESCs, but only SAHA reduced the size of the beating areas in EBs that
      originated from HDAC1 dn mESCs. Additionally, explanted embryonic hearts (e15)
      responded to treatment with HDACi: all of the tested HDACi (TSA, SAHA, VPA)
      increased the levels of H3K9ac, H4ac, H4K20ac, and pan-acetylated lysines in
      embryonic hearts. This observation shows that explanted tissue can be maintained
      in a hyperacetylation state several hours after excision, which appears to be
      useful information from the view of transplantation strategy and the maintenance
      of gene upregulation via acetylation in tissue intended for transplantation.

PMID- 30115892
TI  - Purification and Characterization of a Novel Antiplatelet Peptide from
      Deinagkistrodon acutus Venom.
AB  - Animal venoms are considered as one of the most important sources for drug
      development. Deinagkistrodon acutus is famous for its toxicity to the human
      hematological system and envenomed patients develop a coagulation disorder with
      the symptoms of hemorrhage and microthrombi formation. The purpose of this study
      was to separate antiplatelet peptides from D. acutus venom using a combination of
      an ultrafiltration technique and reversed-phase high performance liquid
      chromatography (HPLC), which was guided by monitoring antiplatelet aggregation
      bioactivity. A novel octa-peptide named DAA-8 was found. This peptide inhibited
      protease-activated receptor1 (PAR-1) agonist (SFLLRN-NH2) induced platelet
      aggregation and it also inhibited platelet aggregation induced by thrombin, ADP,
      and collagen. Furthermore, DAA-8 showed significant antithrombotic activity and
      resulted in a slightly increased bleeding risk in vivo. This is the first report
      of a peptide derived from snake venom, which inhibited PAR-1 agonist-induced
      platelet aggregation. This peptide may provide a template to design a new PAR-1
      inhibitor.

PMID- 30115893
TI  - Centralized Fusion Approach to the Estimation Problem with Multi-Packet
      Processing under Uncertainty in Outputs and Transmissions.
AB  - This paper is concerned with the least-squares linear centralized estimation
      problem in multi-sensor network systems from measured outputs with uncertainties
      modeled by random parameter matrices. These measurements are transmitted to a
      central processor over different communication channels, and owing to the
      unreliability of the network, random one-step delays and packet dropouts are
      assumed to occur during the transmissions. In order to avoid network congestion,
      at each sampling time, each sensor's data packet is transmitted just once, but
      due to the uncertainty of the transmissions, the processing center may receive
      either one packet, two packets, or nothing. Different white sequences of
      Bernoulli random variables are introduced to describe the observations used to
      update the estimators at each sampling time. To address the centralized
      estimation problem, augmented observation vectors are defined by accumulating the
      raw measurements from the different sensors, and when the current measurement of
      a sensor does not arrive on time, the corresponding component of the augmented
      measured output predictor is used as compensation in the estimator design.
      Through an innovation approach, centralized fusion estimators, including
      predictors, filters, and smoothers are obtained by recursive algorithms without
      requiring the signal evolution model. A numerical example is presented to show
      how uncertain systems with state-dependent multiplicative noise can be covered by
      the proposed model and how the estimation accuracy is influenced by both sensor
      uncertainties and transmission failures.

PMID- 30115894
TI  - Functionalized Silver Nano-Sensor for Colorimetric Detection of Hg2+ Ions: Facile
      Synthesis and Docking Studies.
AB  - In the present study, we describe the facile synthesis of silver nanoparticles
      (AgNPs) and their nanostructures functionalized with 2-aminopyrimidine-4,6-diol
      (APD-AgNPs) for Hg2+ ion detection. The promising colorimetric response of APD
      AgNPs to detect Hg2+ ions was visible with naked eyes and spectroscopic changes
      were examined by using a UV-Visible spectrophotometer. The aggregation of APD
      AgNPs upon addition of Hg2+ ions was due to the chelation effect of the
      functionalized nanostructures and results in a color change from pale brown to
      deep yellow color. The probing sensitivity was observed within five minutes with
      a detection limit of about 0.35 uM/L. The TEM images of APD-AgNPs showed
      polydispersed morphologies with hexagonal, heptagonal and spherical
      nanostructures with an average size between 10 to 40 nm. Furthermore, the sensing
      behavior of APD-AgNPs towards Hg2+ ions detection was investigated using docking
      and interaction studies.

PMID- 30115895
TI  - Temporal Variation of Chlorophyll-a Concentrations in Highly Dynamic Waters from
      Unattended Sensors and Remote Sensing Observations.
AB  - Monitoring of water quality changes in highly dynamic inland lakes is frequently
      impeded by insufficient spatial and temporal coverage, for both field surveys and
      remote sensing methods. To track short-term variations of chlorophyll
      fluorescence and chlorophyll-a concentrations in Poyang Lake, the largest
      freshwater lake in China, high-frequency, in-situ, measurements were collected
      from two fixed stations. The K-mean clustering method was also applied to
      identify clusters with similar spatio-temporal variations, using remote sensing
      Chl-a data products from the MERIS satellite, taken from 2003 to 2012. Four lake
      area classes were obtained with distinct spatio-temporal patterns, two of which
      were selected for in situ measurement. Distinct daily periodic variations were
      observed, with peaks at approximately 3:00 PM and troughs at night or early
      morning. Short-term variations of chlorophyll fluorescence and Chl-a levels were
      revealed, with a maximum intra-diurnal ratio of 5.1 and inter-diurnal ratio of
      7.4, respectively. Using geostatistical analysis, the temporal range of
      chlorophyll fluorescence and corresponding Chl-a variations was determined to be
      9.6 h, which indicates that there is a temporal discrepancy between Chl-a
      variations and the sampling frequency of current satellite missions. An analysis
      of the optimal sampling strategies demonstrated that the influence of the
      sampling time on the mean Chl-a concentrations observed was higher than 25%, and
      the uncertainty of any single Terra/MODIS or Aqua/MODIS observation was
      approximately 15%. Therefore, sampling twice a day is essential to resolve Chl-a
      variations with a bias level of 10% or less. The results highlight short-term
      variations of critical water quality parameters in freshwater, and they help
      identify specific design requirements for geostationary earth observation
      missions, so that they can better address the challenges of monitoring complex
      coastal and inland environments around the world.

PMID- 30115896
TI  - Interaction between Tumor-Associated Dendritic Cells and Colon Cancer Cells
      Contributes to Tumor Progression via CXCL1.
AB  - Crosstalk of a tumor with its microenvironment is a critical factor contributing
      to cancer development. This study investigates the soluble factors released by
      tumor-associated dendritic cells (TADCs) responsible for increasing cancer stem
      cell (CSC) properties, cell mobility, and epithelial-to-mesenchymal transition
      (EMT). Dendritic cells (DCs) of colon cancer patients were collected for
      phenotype and CXCL1 expression by flow cytometry and Luminex assays. The
      transcriptome of CXCL1-treated cancer cells was established by next generation
      sequencing. Inflammatory chemokine CXCL1, present in large amounts in DCs
      isolated from colon cancer patients, and SW620-conditioned TADCs, enhance CSC
      characteristics in cancer, supported by enhanced anchorage-independent growth,
      CD133 expression and aldehyde dehydrogenase activity. Additionally, CXCL1
      increases the metastatic ability of a cancer by enhancing cell migration, matrix
      metalloproteinase-7 expression and EMT. The enhanced CXCL1 expression in DCs is
      also noted in mice transplanted with colon cancer cells. Transcriptome analysis
      of CXCL1-treated SW620 cells indicates that CXCL1 increases potential oncogene
      expression in colon cancer, including PTHLH, TYRP1, FOXO1, TCF4 and ZNF880.
      Concurrently, CXCL1 displays a specific microRNA (miR) upregulated by the
      prototypical colon cancer onco-miR miR-105. Analysis of publicly available data
      reveals CXCL1-driven oncogenes and miR-105 have a negative prognostic impact on
      the outcome of colon cancer. This study indicates a new mechanism by which the
      colon cancer milieu exploits DC plasticity to support cancer progression.

PMID- 30115898
TI  - Effects of Loading Frequency and Loading Type on High-Cycle and Very-High-Cycle
      Fatigue of a High-Strength Steel.
AB  - High-cycle and very-high-cycle fatigue tests via rotary bending (52.5 Hz),
      electromagnetic resonance (120 Hz) axial cycling, and ultrasonic (20 kHz) axial
      cycling were performed for a high-strength steel with three heat treatment
      conditions, and the effects of loading frequency and loading type on fatigue
      strength and fatigue life were investigated. The results revealed that the
      loading frequency effect is caused by the combined response of strain rate
      increase and induced temperature rise. A parameter eta was proposed to judge the
      occurrence of loading frequency effect, and the calculated results were in
      agreement with the experimental data. In addition, a statistical method based on
      the control volume was used to reconcile the effect of loading type, and the
      predicted data were consistent with the experimental results.

PMID- 30115899
TI  - Silver Nanoparticles and Polyphenol Inclusion Compounds Composites for
      Phytophthora cinnamomi Mycelial Growth Inhibition.
AB  - Phytophthora cinnamomi, responsible for "root rot" or "dieback" plant disease,
      causes a significant amount of economic and environmental impact. In this work,
      the fungicide action of nanocomposites based on silver nanoparticles and
      polyphenol inclusion compounds, which feature enhanced bioavailability and water
      solubility, was assayed for the control of this soil-borne water mold. Inclusion
      compounds were prepared by an aqueous two-phase system separation method through
      extraction, either in an hydroalcoholic solution with chitosan oligomers (COS) or
      in a choline chloride:urea:glycerol deep eutectic solvent (DES). The new
      inclusion compounds were synthesized from stevioside and various polyphenols
      (gallic acid, silymarin, ferulic acid and curcumin), in a [6:1] ratio in the COS
      medium and in a [3:1] ratio in the DES medium, respectively. Their in vitro
      response against Phytophthora cinnamomi isolate MYC43 (at concentrations of 125,
      250 and 500 ug.mL-1) was tested, which found a significant mycelial growth
      inhibition, particularly high for the composites prepared using DES. Therefore,
      these nanocomposites hold promise as an alternative to fosetyl-Al and metalaxyl
      conventional systemic fungicides.

PMID- 30115897
TI  - Suppression of Schistosoma japonicum Acetylcholinesterase Affects Parasite Growth
      and Development.
AB  - To further investigate the importance of Schistosoma japonicum
      acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and
      development, we used RNA interference (RNAi) to knock-down its expression in
      adults and eggs in vitro. This resulted in its reduced transcription but also
      expression of other important genes involved both in cholinergic signaling and
      glucose uptake were impacted substantially. Significant decreases in AChE protein
      expression, AChE enzymatic activity, and glucose uptake were observed in the
      SjAChE-knockdown parasites compared with luciferase controls. In
      vaccine/challenge experiments, we found that immunization of mice with
      recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in
      male worm numbers (33%), liver granuloma density (41%), and reduced numbers of
      mature intestinal eggs (73%) in the vaccinated group compared with the control
      group. These results indicate AChE plays an important role in the metabolism of
      male worms, and impacts indirectly on female fecundity leading to increased
      numbers of immature eggs being released and reduced sizes of liver granulomas.
      Furthermore, cytokine analysis showed that immunization of mice with rSjAChE
      elicited a predominantly Th1-type immune response characterized by increased
      production of IFNgamma in splenic CD4+ T cells of vaccinated mice. The study
      confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic
      schistosomiasis japonica.

PMID- 30115900
TI  - Correlation of Brain Perfusion with White Matter Hyperintensity, Brain Atrophy,
      and Cognition in Patients with Posterior Cerebral Artery Stenosis and Subjective
      Cognitive Decline.
AB  - BACKGROUND This study aimed to investigate the correlation of brain perfusion
      with white matter hyperintensity (WMH), brain atrophy, and cognition in patients
      with moderate to severe posterior cerebral artery stenosis (PCAS). MATERIAL AND
      METHODS 65 patients with memory decline as the main complaint and no history of
      brain infarction were recruited from the Department of Neurology of Tongji
      Hospital. Patients with moderate to severe PCAS were included in case group, and
      subjects with normal intracranial blood vessels served as controls. The
      demographics and vascular risk factors were recorded. Montreal Cognitive
      Assessment (MoCA) was used to evaluate the cognition. CT perfusion imaging was
      performed, and WASID was employed for the assessment of intracranial artery
      stenosis. The region of interest (ROI) was analyzed based on the whole brain
      perfusion. Cranial MRI was performed, and Scheltens scoring system was used for
      the assessment of WMH on FLAIR. T1 weighed images were obtained, and global
      cortical atrophy (GCA) scale was employed for the assessment of brain atrophy.
      The detections of brain perfusion, WMH and brain atrophy were done at centrum
      ovale, parietal lateral ventricle and basal ganglia layers. RESULTS In PCAS
      patients we found low perfusion in the antecornu and postcornu blood supply areas
      at the lateral ventricle, the blood supply area of the anterior cerebral artery,
      the blood supply area of the posterior cerebral artery, and the blood supply area
      at the hippocampus as compared with control subjects (p<0.05). As compared with
      control subjects, the incidence of WMH in the blood supply areas at the deep
      brain and lateral ventricle was significantly higher in PCAS patients (p<0.05).
      When compared with controls, the incidence of brain atrophy increased
      significantly in PCAS patients (p<0.01). Correlation analysis showed the brain
      perfusion at the blood supply area of the posterior cerebral artery was
      positively correlated to the total MoCA score and negatively correlated to the
      severity of WMH at the blood supply area of the posterior cerebral artery
      (p<0.05). Further analysis showed the brain perfusion at the blood supply area of
      the posterior cerebral artery was negatively associated with cortex supplied by
      the posterior cerebral artery, posterior cingulate, and hippocampus (p<0.01).
      CONCLUSIONS PCAS patients have a higher incidence of brain atrophy, and the
      perfusion at the area supplied by the posterior cerebral artery is correlated to
      the severity of brain atrophy and of WMH, as well as to cognition decline.

PMID- 30115901
TI  - The Efficacy of Rabbit Anti-Thymocyte Globulin for Acute Kidney Transplant
      Rejection in Patients Using Calcineurin Inhibitor and Mycophenolate Mofetil-Based
      Immunosuppressive Therapy.
AB  - BACKGROUND T cell depleting antibody therapy with rabbit anti-thymocyte globulin
      (rATG) is the treatment of choice for glucocorticoid-resistant acute kidney
      allograft rejection (AR) and is used as first-line therapy in severe AR. Almost
      all studies investigating the effectiveness of rATG for this indication were
      conducted at the time when cyclosporine A and azathioprine were the standard of
      care. Here, the long-term outcome of rATG for AR in patients using the current
      standard immunosuppressive therapy (i.e., tacrolimus and mycophenolate mofetil)
      is described. MATERIAL AND METHODS Between 2002 to 2012, 108 patients were
      treated with rATG for AR. Data on kidney function in the year following rATG and
      long-term outcomes were collected. RESULTS Overall survival after rATG was
      comparable to overall survival of all kidney transplantation patients (P=0.10).
      Serum creatinine 1 year after rATG was 179 umol/L (interquartile range (IQR) 136
      234 umol/L) and was comparable to baseline serum creatinine (P=0.22). Early AR
      showed better allograft survival than late AR (P=0.0007). In addition, 1 year
      after AR, serum creatinine was lower in early AR (157 mol/L; IQR 131-203)
      compared to late AR (216 mol/L; IQR 165-269; P<0.05). The Banff grade of
      rejection, kidney function at the moment of rejection, and reason for rATG
      (severe or glucocorticoid resistant AR) did not influence the allograft survival.
      CONCLUSIONS Treatment of AR with rATG is effective in patients using current
      standard immunosuppressive therapy, even in patients with poor allograft
      function. Early identification of AR followed by T cell depleting treatment leads
      to better allograft outcomes.

PMID- 30115902
TI  - Retropharyngeal Hematoma as an Unusual Presentation of Myelodysplastic Syndrome:
      A Case Report.
AB  - BACKGROUND Retropharyngeal hematoma is a relatively rare diagnosis that requires
      a high clinical suspicion and stabilization of the airway to prevent rapid
      deterioration. We report a case of a spontaneous retropharyngeal hematoma in an
      elderly patient with myelodysplastic syndrome and associated thrombocytopenia.
      CASE REPORT A 90-year-old man with myelodysplastic syndrome was brought to the
      Emergency Department with complaints of difficulty swallowing and muffled voice
      for 24 hours. Upon arrival, his vital signs and physical exam were unremarkable,
      except that when he was asked to take a sip of water, he could not swallow it.
      Complete blood count was remarkable for leukocytosis of 14.3*103/mcL, hemoglobin
      of 9.0 gm/dL, and platelet count of 26*103/mcL. Chest X-ray and lateral soft
      tissue neck X-rays were grossly unremarkable. The patient was admitted for
      further evaluation and was scheduled for esophagogastroduodenoscopy. During
      intubation for esophagogastroduodenoscopy, the patient was noted to have
      significant airway narrowing. A subsequent CT scan revealed a 3*2*2 cm
      supraglottic hypodensity, thought to represent a retropharyngeal hematoma. The
      patient was transferred to the Intensive Care Unit (ICU) and received platelet
      transfusions. The ICU course was complicated by anemia, which necessitated
      transfusion of packed red blood cells. On hospital day 7, the patient reported
      resolution of his symptoms and was discharged home. CONCLUSIONS This case adds to
      the growing body of literature on spontaneous retropharyngeal hematomas. High
      clinical suspicion is warranted in patients who present with acute dysphagia,
      odynophagia, and dysphonia. Prompt imaging and airway management are vital in
      managing patients with this condition.

PMID- 30115903
TI  - Biological function of eosinophil extracellular traps in patients with severe
      eosinophilic asthma.
AB  - Eosinophil extracellular traps (EETs), a complex of DNA fibers and cytotoxic
      granule proteins, are implicated in the development of asthma; however, the
      pathophysiological function of EETs in immune responses has not been fully
      determined. The present study investigated the characteristics of EETs from
      patients with non-severe asthma (NSA, n = 20) and severe eosinophilic asthma
      (SEA, n = 20) and evaluated EET function. The percentage of EET-forming
      peripheral blood eosinophils stimulated with IL-5 and LPS was significantly
      higher in patients with SEA than in those with NSA (P = 0.009). This percentage
      negatively correlated with baseline FEV1 (r = -0.350, P = 0.027) and positively
      correlated with serum eosinophil-derived neurotoxin levels in asthmatic subjects
      (r = 0.437, P = 0.018). In addition, EET formation was markedly associated with
      reactive oxygen species production (r = 0.750, P < 0.001). These EETs exhibited
      an autocrine function to induce eosinophil degranulation, which led to granule
      protein production. Airway epithelial cells stimulated with EETs exhibited
      increased epithelial detachment and permeability and pro-inflammatory cytokine
      release. However, EETs were not significantly associated with mast cell
      activation. The present study suggests that peripheral blood eosinophils from
      patients with SEA may be more activated to produce EETs than those from patients
      with NSA, which further induces inflammation in asthmatic airways. Therefore,
      regulation of EET formation and function may be a novel therapeutic approach for
      asthma management.

PMID- 30115905
TI  - Local structure in deeply supercooled liquids exhibits growing lengthscales and
      dynamical correlations.
AB  - Glasses are among the most widely used of everyday materials, yet the process by
      which a liquid's viscosity increases by 14 decades to become a glass remains
      unclear, as often contradictory theories provide equally good descriptions of the
      available data. Knowledge of emergent lengthscales and higher-order structure
      could help resolve this, but this requires time-resolved measurements of dense
      particle coordinates-previously only obtained over a limited time interval. Here
      we present an experimental study of a model colloidal system over a dynamic
      window significantly larger than previous measurements, revealing structural
      ordering more strongly linked to dynamics than previously found. Furthermore we
      find that immobile regions and domains of local structure grow concurrently with
      density, and that these regions have low configurational entropy. We thus show
      that local structure plays an important role at deep supercooling, consistent
      with a thermodynamic interpretation of the glass transition rather than a
      principally dynamic description.

PMID- 30115906
TI  - Enantioselective radical conjugate additions driven by a photoactive
      intramolecular iminium-ion-based EDA complex.
AB  - The photochemical activity of electron donor-acceptor (EDA) complexes provides a
      way to generate radicals under mild conditions. This strategy has found
      application in chemical synthesis and recently in enantioselective catalysis.
      Reported methods classically relied on the formation of intermolecular EDA
      complexes, generated upon aggregation of two suitable reagents. Herein, we
      further expand the synthetic utility of this strategy demonstrating that an
      intramolecular EDA complex can trigger a photochemical catalytic enantioselective
      radical process. This approach enables radical conjugate additions to beta
      substituted cyclic enones to form quaternary carbon stereocenters with high
      stereocontrol using visible light irradiation. Crucial for success is the use of
      an amine catalyst, adorned with a carbazole moiety, which generates, upon
      condensation with enones, chiral iminium ions that show a broad absorption band
      in the visible region. This optical property originates from an intramolecular
      charge transfer pi-pi interaction between the electron-rich carbazole nucleus and
      the electron-deficient iminium double bond.

PMID- 30115904
TI  - Mechanisms regulating intestinal barrier integrity and its pathological
      implications.
AB  - The gastrointestinal tract is a specialized organ in which dynamic interactions
      between host cells and the complex environment occur in addition to food
      digestion. Together with the chemical barrier of the mucosal layer and the
      cellular immune system, the epithelial cell layer performs a pivotal role as the
      first physical barrier against external factors and maintains a symbiotic
      relationship with commensal bacteria. The tight junction proteins, including
      occludin, claudins, and zonula occludens, are crucial for the maintenance of
      epithelial barrier integrity. To allow the transport of essential molecules and
      restrict harmful substances, the intracellular signaling transduction system and
      a number of extracellular stimuli such as cytokines, small GTPases, and post
      translational modifications dynamically modulate the tight junction protein
      complexes. An imbalance in these regulations leads to compromised barrier
      integrity and is linked with pathological conditions. Despite the obscurity of
      the causal relationship, the loss of barrier integrity is considered to
      contribute to inflammatory bowel disease, obesity, and metabolic disorders. The
      elucidation of the role of diseases in barrier integrity and the underlying
      regulatory mechanisms have improved our understanding of the intestinal barrier
      to allow the development of novel and potent therapeutic approaches.

PMID- 30115909
TI  - Author Correction: An NF-kappaB-microRNA regulatory network tunes macrophage
      inflammatory responses.
AB  - Li-Fan Lu and Alexander Y. Rudensky, who supplied miR-146a floxed mice used in
      this study, were inadvertently omitted from the author list in the originally
      published version of this Article. This has now been corrected in both the PDF
      and HTML versions of the Article. The generation of the floxed mice has been
      described in detail by Cho and Lee et al.1.

PMID- 30115908
TI  - Observation of bosonic condensation in a hybrid monolayer MoSe2-GaAs microcavity.
AB  - Bosonic condensation belongs to the most intriguing phenomena in physics, and was
      mostly reserved for experiments with ultra-cold quantum gases. More recently, it
      became accessible in exciton-based solid-state systems at elevated temperatures.
      Here, we demonstrate bosonic condensation driven by excitons hosted in an
      atomically thin layer of MoSe2, strongly coupled to light in a solid-state
      resonator. The structure is operated in the regime of collective strong coupling
      between a Tamm-plasmon resonance, GaAs quantum well excitons, and two-dimensional
      excitons confined in the monolayer crystal. Polariton condensation in a monolayer
      crystal manifests by a superlinear increase of emission intensity from the hybrid
      polariton mode, its density-dependent blueshift, and a dramatic collapse of the
      emission linewidth, a hallmark of temporal coherence. Importantly, we observe a
      significant spin-polarization in the injected polariton condensate, a fingerprint
      for spin-valley locking in monolayer excitons. Our results pave the way towards
      highly nonlinear, coherent valleytronic devices and light sources.

PMID- 30115907
TI  - Size control in mammalian cells involves modulation of both growth rate and cell
      cycle duration.
AB  - Despite decades of research, how mammalian cell size is controlled remains
      unclear because of the difficulty of directly measuring growth at the single-cell
      level. Here we report direct measurements of single-cell volumes over entire cell
      cycles on various mammalian cell lines and primary human cells. We find that, in
      a majority of cell types, the volume added across the cell cycle shows little or
      no correlation to cell birth size, a homeostatic behavior called "adder". This
      behavior involves modulation of G1 or S-G2 duration and modulation of growth
      rate. The precise combination of these mechanisms depends on the cell type and
      the growth condition. We have developed a mathematical framework to compare size
      homeostasis in datasets ranging from bacteria to mammalian cells. This reveals
      that a near-adder behavior is the most common type of size control and highlights
      the importance of growth rate modulation to size control in mammalian cells.

PMID- 30115910
TI  - Mechanical glass transition revealed by the fracture toughness of metallic
      glasses.
AB  - The fracture toughness of glassy materials remains poorly understood. In large
      part, this is due to the disordered, intrinsically non-equilibrium nature of the
      glass structure, which challenges its theoretical description and experimental
      determination. We show that the notch fracture toughness of metallic glasses
      exhibits an abrupt toughening transition as a function of a well-controlled
      fictive temperature (Tf), which characterizes the average glass structure. The
      ordinary temperature, which has been previously associated with a ductile-to
      brittle transition, is shown to play a secondary role. The observed transition is
      interpreted to result from a competition between the Tf-dependent plastic
      relaxation rate and an applied strain rate. Consequently, a similar toughening
      transition as a function of strain rate is predicted and demonstrated
      experimentally. The observed mechanical toughening transition bears strong
      similarities to the ordinary glass transition and explains the previously
      reported large scatter in fracture toughness data and ductile-to-brittle
      transitions.

PMID- 30115911
TI  - Effect of valproate and pregabalin on human anxiety-like behaviour in a
      randomised controlled trial.
AB  - Valproate is an anticonvulsant drug with strong preclinical evidence for reducing
      anxiety behaviour in rodents but no clear clinical evidence. To motivate clinical
      trials, we here investigate the use of valproate in a translational human model
      of anxiety behaviour. In a double-blind, randomised, placebo-controlled trial, n
      = 118 healthy participants played a previously validated approach/avoidance
      conflict computer game to measure anxiety-like behaviour, while under 400 mg
      valproate, under 200 mg of the established anxiolytic/anticonvulsant pregabalin,
      or under placebo. Saccadic peak velocity and subjective ratings were assessed to
      control for drug-induced sedation. Compared to placebo, valproate and pregabaline
      were anxiolytic in the primary outcome, and several secondary outcomes. Bayesian
      model comparison decisively demonstrated no differences between the two drugs.
      Subjective and objective sedation was significantly more pronounced under
      pregabalin than valproate, but did not explain anxiolytic effects. We demonstrate
      acute anxiolytic properties of valproate in healthy humans. Both drugs have
      similar anxiolytic properties at the doses used. Valproate is less sedative than
      pregabalin. Our results suggest clinical trials on the use of valproate in
      anxiolytic treatment. More generally, we propose a strategy of screening drugs in
      human preclinical models that can directly be compared across species, such as
      the approach/avoidance conflict computer game used here. This approach could thus
      facilitate translational anxiety research.

PMID- 30115912
TI  - Adiporon, an adiponectin receptor agonist acts as an antidepressant and metabolic
      regulator in a mouse model of depression.
AB  - Major depression is a psychiatric disorder with complex etiology. About 30% of
      depressive patients are resistant to antidepressants that are currently
      available, likely because they only target the monoaminergic systems. Thus,
      identification of novel antidepressants with a larger action spectrum is urgently
      required. Epidemiological data indicate high comorbidity between metabolic and
      psychiatric disorders, particularly obesity and depression. We used a well
      characterized anxiety/depressive-like mouse model consisting of continuous input
      of corticosterone for seven consecutive weeks. A panel of reliable behavioral
      tests were conducted to assessing numerous facets of the depression-like state,
      including anxiety, resignation, reduced motivation, loss of pleasure, and social
      withdrawal. Furthermore, metabolic features including weight, adiposity, and
      plasma biological parameters (lipids, adipokines, and cytokines) were
      investigated in corticosterone-treated mice. Our data show that chronic
      administration of corticosterone induced the parallel onset of metabolic and
      behavioral dysfunctions in mice. AdipoRon, a potent adiponectin receptor agonist,
      prevented the corticosterone-induced early onset of moderate obesity and
      metabolic syndromes. Moreover, in all the behavioral tests, daily treatment with
      AdipoRon successfully reversed the corticosterone-induced depression-like state
      in mice. AdipoRon exerted its pleiotropic actions on various systems including
      hippocampal neurogenesis, serotonergic neurotransmission, neuroinflammation, and
      the tryptophan metabolic pathway, which can explain its antidepressant
      properties. Our study highlights the pivotal role of the adiponergic system in
      the development of both metabolic and psychiatric disorders. AdipoRon may
      constitute a promising novel antidepressant.

PMID- 30115914
TI  - Correction: Long non-coding RNA LINC00152 promotes cell proliferation,
      metastasis, and confers 5-FU resistance in colorectal cancer by inhibiting miR
      139-5p.
AB  - This article was originally published under Nature Research's License to Publish,
      but now has been made available under a CC BY 4.0 license. The PDF and HTML
      versions of the Article have been modified accordingly.

PMID- 30115913
TI  - Transcriptomic signatures of schizophrenia revealed by dopamine perturbation in
      an ex vivo model.
AB  - The dopaminergic hypothesis of schizophrenia (SZ) postulates that dopaminergic
      over activity causes psychosis, a central feature of SZ, based on the observation
      that blocking dopamine (DA) improves psychotic symptoms. DA is known to have both
      receptor- and non-receptor-mediated effects, including oxidative mechanisms that
      lead to apoptosis. The role of DA-mediated oxidative processes in SZ has been
      little studied. Here, we have used a cell perturbation approach and measured
      transcriptomic profiles by RNAseq to study the effect of DA exposure on
      transcription in B-cell transformed lymphoblastoid cell lines (LCLs) from 514 SZ
      cases and 690 controls. We found that DA had widespread effects on both cell
      growth and gene expression in LCLs. Overall, 1455 genes showed statistically
      significant differential DA response in SZ cases and controls. This set of
      differentially expressed genes is enriched for brain expression and for functions
      related to immune processes and apoptosis, suggesting that DA may play a role in
      SZ pathogenesis through modulating those systems. Moreover, we observed a non
      significant enrichment of genes near genome-wide significant SZ loci and with
      genes spanned by SZ-associated copy number variants (CNVs), which suggests
      convergent pathogenic mechanisms detected by both genetic association and gene
      expression. The study suggests a novel role of DA in the biological processes of
      immune and apoptosis that may be relevant to SZ pathogenesis. Furthermore, our
      results show the utility of pathophysiologically relevant perturbation
      experiments to investigate the biology of complex mental disorders.

PMID- 30115916
TI  - Biased genome editing using the local accumulation of DSB repair molecules
      system.
AB  - Selective genome editing such as gene knock-in has recently been achieved by
      administration of chemical enhancer or inhibitor of particular DNA double-strand
      break (DSB) repair pathways, as well as overexpression of pathway-specific genes.
      In this study, we attempt to enhance the efficiency further to secure robust gene
      knock-ins, by using the local accumulation of DSB repair molecules (LoAD) system.
      We identify CtIP as a strong enhancer of microhomology-mediated end-joining
      (MMEJ) repair by genetic screening, and show the knock-in-enhancing effect of
      CtIP LoADing. Next-generation sequencing reveals that CtIP LoADing highly
      increases the frequency of MMEJ-mediated integration. Selection-free,
      simultaneous triple gene knock-ins are also achieved with the CtIP-LoADing
      strategy. Moreover, by replacing the LoADing molecules and targeting strategies,
      this system can be applied for other specific genome engineering purposes, such
      as introducing longer deletions for gene disruption, independently introducing
      multiple mutations without chromosomal deletion, and efficiently incorporating a
      single-stranded oligodeoxynucleotide donor.

PMID- 30115915
TI  - Symmetry breakdown of 4,4"-diamino-p-terphenyl on a Cu(111) surface by lattice
      mismatch.
AB  - Site-selective functionalization of only one of two identical chemical groups
      within one molecule is highly challenging, which hinders the production of
      complex organic macromolecules. Here we demonstrate that adsorption of 4,4"
      diamino-p-terphenyl on a metal surface leads to a dissymmetric binding affinity.
      With low temperature atomic force microscopy, using CO-tip functionalization, we
      reveal the asymmetric adsorption geometries of 4,4"-diamino-p-terphenyl on
      Cu(111), while on Au(111) the symmetry is retained. This symmetry breaking on
      Cu(111) is caused by a lattice mismatch and interactions with the subsurface
      atomic layer. The dissymmetry results in a change of the binding affinity of one
      of the amine groups, leading to a non-stationary behavior under the influence of
      the scanning tip. Finally, we exploit this dissymmetric binding affinity for on
      surface self-assembly with 4,4"-diamino-p-terphenyl for side-preferential
      attachment of 2-triphenylenecarbaldehyde. Our findings provide a new route
      towards surface-induced dissymmetric activation of a symmetric compound.

PMID- 30115917
TI  - Surveying silicon nitride nanopores for glycomics and heparin quality assurance.
AB  - Polysaccharides have key biological functions and can be harnessed for
      therapeutic roles, such as the anticoagulant heparin. Their complexity-e.g., >100
      monosaccharides with variety in linkage and branching structure-significantly
      complicates analysis compared to other biopolymers such as DNA and proteins.
      More, and improved, analysis tools have been called for, and here we demonstrate
      that solid-state silicon nitride nanopore sensors and tuned sensing conditions
      can be used to reliably detect native polysaccharides and enzymatic digestion
      products, differentiate between different polysaccharides in straightforward
      assays, provide new experimental insights into nanopore electrokinetics, and
      uncover polysaccharide properties. We show that nanopore sensing allows us to
      easily differentiate between a clinical heparin sample and one spiked with the
      contaminant that caused deaths in 2008 when its presence went undetected by
      conventional assays. The work reported here lays a foundation to further explore
      polysaccharide characterization and develop assays using thin-film solid-state
      nanopore sensors.

PMID- 30115918
TI  - Probing warm dense matter using femtosecond X-ray absorption spectroscopy with a
      laser-produced betatron source.
AB  - Exploring and understanding ultrafast processes at the atomic level is a
      scientific challenge. Femtosecond X-ray absorption spectroscopy (XAS) arises as
      an essential experimental probing method, as it can simultaneously reveal both
      electronic and atomic structures, and thus potentially unravel their
      nonequilibrium dynamic interplay which is at the origin of most of the ultrafast
      mechanisms. However, despite considerable efforts, there is still no femtosecond
      X-ray source suitable for routine experiments. Here we show that betatron
      radiation from relativistic laser-plasma interaction combines ideal features for
      femtosecond XAS. It has been used to investigate the nonequilibrium dynamics of a
      copper sample brought at extreme conditions of temperature and pressure by a
      femtosecond laser pulse. We measured a rise-time of the electron temperature
      below 100 fs. This experiment demonstrates the great potential of the table-top
      betatron source which makes possible the investigation of unexplored ultrafast
      processes in manifold fields of research.

PMID- 30115919
TI  - Single-particle mass spectrometry with arrays of frequency-addressed
      nanomechanical resonators.
AB  - One of the main challenges to overcome to perform nanomechanical mass
      spectrometry analysis in a practical time frame stems from the size mismatch
      between the analyte beam and the small nanomechanical detector area. We report
      here the demonstration of mass spectrometry with arrays of 20 multiplexed
      nanomechanical resonators; each resonator is designed with a distinct resonance
      frequency which becomes its individual address. Mass spectra of metallic
      aggregates in the MDa range are acquired with more than one order of magnitude
      improvement in analysis time compared to individual resonators. A 20 NEMS array
      is probed in 150 ms with the same mass limit of detection as a single resonator.
      Spectra acquired with a conventional time-of-flight mass spectrometer in the same
      system show excellent agreement. We also demonstrate how mass spectrometry
      imaging at the single-particle level becomes possible by mapping a 4-cm-particle
      beam in the MDa range and above.

PMID- 30115920
TI  - Discovery of cationic nonribosomal peptides as Gram-negative antibiotics through
      global genome mining.
AB  - The worldwide prevalence of infections caused by antibiotic-resistant Gram
      negative bacteria poses a serious threat to public health due to the limited
      therapeutic alternatives. Cationic peptides represent a large family of
      antibiotics and have attracted interest due to their diverse chemical structures
      and potential for combating drug-resistant Gram-negative pathogens. Here, we
      analyze 7395 bacterial genomes to investigate their capacity for biosynthesis of
      cationic nonribosomal peptides with activity against Gram-negative bacteria.
      Applying this approach, we identify two novel compounds (brevicidine and
      laterocidine) showing bactericidal activities against antibiotic-resistant Gram
      negative pathogens, such as Pseudomonas aeruginosa and colistin-resistant
      Escherichia coli, and an apparently low risk of resistance. The two peptides show
      efficacy against E. coli in a mouse thigh infection model. These findings may
      contribute to the discovery and development of Gram-negative antibiotics.

PMID- 30115921
TI  - Alcoholic liver disease.
AB  - Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease
      worldwide. ALD can progress from alcoholic fatty liver (AFL) to alcoholic
      steatohepatitis (ASH), which is characterized by hepatic inflammation. Chronic
      ASH can eventually lead to fibrosis and cirrhosis and in some cases
      hepatocellular cancer (HCC). In addition, severe ASH (with or without cirrhosis)
      can lead to alcoholic hepatitis, which is an acute clinical presentation of ALD
      that is associated with liver failure and high mortality. Most individuals
      consuming >40 g of alcohol per day develop AFL; however, only a subset of
      individuals will develop more advanced disease. Genetic, epigenetic and non
      genetic factors might explain the considerable interindividual variation in ALD
      phenotype. The pathogenesis of ALD includes hepatic steatosis, oxidative stress,
      acetaldehyde-mediated toxicity and cytokine and chemokine-induced inflammation.
      Diagnosis of ALD involves assessing patients for alcohol use disorder and signs
      of advanced liver disease. The degree of AFL and liver fibrosis can be determined
      by ultrasonography, transient elastography, MRI, measurement of serum biomarkers
      and liver biopsy histology. Alcohol abstinence achieved by psychosomatic
      intervention is the best treatment for all stages of ALD. In the case of advanced
      disease such as cirrhosis or HCC, liver transplantation may be required. Thus,
      new therapies are urgently needed.

PMID- 30115923
TI  - Alcoholic liver disease.

PMID- 30115922
TI  - Simulations tackle abrupt massive migrations of energetic beam ions in a tokamak
      plasma.
AB  - In the late 1990s, fusion scientists at the Japanese tokamak JT-60U discovered
      abrupt large-amplitude events during beam-driven deuterium plasma experiments. A
      large spike in the magnetic fluctuation signal followed by a drop in the neutron
      emission rate indicates that energetic ions abruptly migrate out of the plasma
      core during an intense burst of Alfven waves that lasts only 0.3 ms. With
      continued beam injection, the energetic ion population recovers until the next
      event occurs 40-60 ms later. Here we present results from simulations that
      successfully reproduce multiple migration cycles and report numerical and
      experimental evidence for the multi-mode nature of these intermittent phenomena.
      Moreover, we elucidate the role of collisional slow-down and show that the large
      amplitude Alfvenic fluctuations can drive magnetic reconnection and induce
      macroscopic magnetic islands. In this way, our simulations allow us to gradually
      unravel the underlying physical processes and develop predictive capabilities.

PMID- 30115925
TI  - Understanding voltage decay in lithium-excess layered cathode materials through
      oxygen-centred structural arrangement.
AB  - Lithium-excess 3d-transition-metal layered oxides (Li1+xNiyCozMn1-x-y-zO2, >250
      mAh g-1) suffer from severe voltage decay upon cycling, which decreases energy
      density and hinders further research and development. Nevertheless, the lack of
      understanding on chemical and structural uniqueness of the material prevents the
      interpretation of internal degradation chemistry. Here, we discover a fundamental
      reason of the voltage decay phenomenon by comparing ordered and cation-disordered
      materials with a combination of X-ray absorption spectroscopy and transmission
      electron microscopy studies. The cation arrangement determines the transition
      metal-oxygen covalency and structural reversibility related to voltage decay. The
      identification of structural arrangement with de-lithiated oxygen-centred
      octahedron and interactions between octahedrons affecting the oxygen stability
      and transition metal mobility of layered oxide provides the insight into the
      degradation chemistry of cathode materials and a way to develop high-energy
      density electrodes.

PMID- 30115924
TI  - Emerging Southeast Asian PfCRT mutations confer Plasmodium falciparum resistance
      to the first-line antimalarial piperaquine.
AB  - The widely used antimalarial combination therapy dihydroartemisinin + piperaquine
      (DHA + PPQ) has failed in Cambodia. Here, we perform a genomic analysis that
      reveals a rapid increase in the prevalence of novel mutations in the Plasmodium
      falciparum chloroquine resistance transporter PfCRT following DHA + PPQ
      implementation. These mutations occur in parasites harboring the K13 C580Y
      artemisinin resistance marker. By introducing PfCRT mutations into sensitive Dd2
      parasites or removing them from resistant Cambodian isolates, we show that the
      H97Y, F145I, M343L, or G353V mutations each confer resistance to PPQ, albeit with
      fitness costs for all but M343L. These mutations sensitize Dd2 parasites to
      chloroquine, amodiaquine, and quinine. In Dd2 parasites, multicopy plasmepsin 2,
      a candidate molecular marker, is not necessary for PPQ resistance. Distended
      digestive vacuoles were observed in pfcrt-edited Dd2 parasites but not in
      Cambodian isolates. Our findings provide compelling evidence that emerging
      mutations in PfCRT can serve as a molecular marker and mediator of PPQ
      resistance.

PMID- 30115927
TI  - Large anomalous Hall effect in the chiral-lattice antiferromagnet CoNb3S6.
AB  - An ordinary Hall effect in a conductor arises due to the Lorentz force acting on
      the charge carriers. In ferromagnets, an additional contribution to the Hall
      effect, the anomalous Hall effect (AHE), appears proportional to the
      magnetization. While the AHE is not seen in a collinear antiferromagnet, with
      zero net magnetization, recently it has been shown that an intrinsic AHE can be
      non-zero in non-collinear antiferromagnets as well as in topological materials
      hosting Weyl nodes near the Fermi energy. Here we report a large anomalous Hall
      effect with Hall conductivity of 27 Omega-1 cm-1 in a chiral-lattice
      antiferromagnet, CoNb3S6 consisting of a small intrinsic ferromagnetic component
      (~0.0013 MUB per Co) along c-axis. This small moment alone cannot explain the
      observed size of the AHE. We attribute the AHE to either formation of a complex
      magnetic texture or the combined effect of the small intrinsic moment on the
      electronic band structure.

PMID- 30115926
TI  - Proteomics for blood biomarker exploration of severe mental illness: pitfalls of
      the past and potential for the future.
AB  - Recent improvements in high-throughput proteomic approaches are likely to
      constitute an essential advance in biomarker discovery, holding promise for
      improved personalized care and drug development. These methodologies have been
      applied to study multivariate protein patterns and provide valuable data of
      peripheral tissues. To highlight findings of the last decade for three of the
      most common psychiatric disorders, namely schizophrenia (SZ), bipolar disorder
      (BD), and major depressive disorder (MDD), we queried PubMed. Here we delve into
      the findings from thirty studies, which used proteomics and multiplex immunoassay
      approaches for peripheral blood biomarker exploration. In an explorative
      approach, we ran enrichment analyses in peripheral blood according to these
      results and ascertained the overlap between proteomic findings and genetic loci
      identified in genome-wide association studies (GWAS). The studies we appraised
      demonstrate that proteomics for psychiatric research has been heterogeneous in
      aims and methods and limited by insufficient sample sizes, poorly defined case
      definitions, methodological inhomogeneity, and confounding results constraining
      the conclusions that can be extracted from them. Here, we discuss possibilities
      for overcoming methodological challenges for the implementation of proteomic
      signatures in psychiatric diagnosis and offer an outlook for future
      investigations. To fulfill the promise of proteomics in mental disease
      diagnostics, future research will need large, well-defined cohorts in combination
      with state-of-the-art technologies.

PMID- 30115928
TI  - Enhanced photon collection enables four dimensional fluorescence nanoscopy of
      living systems.
AB  - The theoretically unlimited spatial resolution of fluorescence nanoscopy often
      comes at the expense of time, contrast and increased dose of energy for
      recording. Here, we developed MoNaLISA, for Molecular Nanoscale Live Imaging with
      Sectioning Ability, a nanoscope capable of imaging structures at a scale of 45-65
      nm within the entire cell volume at low light intensities (W-kW cm-2). Our
      approach, based on reversibly switchable fluorescent proteins, features three
      distinctly modulated illumination patterns crafted and combined to gain
      fluorescence ON-OFF switching cycles and image contrast. By maximizing the
      detected photon flux, MoNaLISA enables prolonged (40-50 frames) and large (50 *
      50 um2) recordings at 0.3-1.3 Hz with enhanced optical sectioning ability. We
      demonstrate the general use of our approach by 4D imaging of organelles and fine
      structures in epithelial human cells, colonies of mouse embryonic stem cells,
      brain cells, and organotypic tissues.

PMID- 30115929
TI  - Neural hypersensitivity to pleasant touch in women remitted from anorexia
      nervosa.
AB  - Interoception, or the sensing and integration of bodily state signals, has been
      implicated in anorexia nervosa (AN), given that the hallmark symptoms involve
      food restriction and body image disturbance. Here we focus on brain response to
      the anticipation and experience of affective interoceptive stimuli. Women
      remitted from AN (RAN; N = 18) and healthy comparison women (CW; N = 26)
      underwent a pleasant affective touch paradigm consisting of gentle strokes with a
      soft brush administered to the forearm or palm during functional neuroimaging.
      RAN had a lower brain response relative to CW during anticipation of touch, but a
      greater response when experiencing touch in the right ventral mid-insula. In RAN,
      this reduced anticipatory response was associated with higher levels of harm
      avoidance. Exploratory analyses in RAN also suggested that lower response during
      touch anticipation was associated with greater body dissatisfaction and higher
      perceived touch intensity ratings. This reduced responsivity to the anticipation
      of pleasant affective interoceptive stimuli in association with higher harm
      avoidance, along with an elevated response to the experience of touch, suggests
      an impaired ability in AN to predict and interpret incoming physiological
      stimuli. Impaired interoception may thus impact one's sense of self, thereby
      supporting observations of disturbed body image and avoidance of affective and
      social stimuli. Therapeutic approaches that help AN to better anticipate and
      interpret salient affective stimuli or improve tolerance of interoceptive
      experiences may be an important addition to current interventions.

PMID- 30115930
TI  - Intracellular interleukin-32gamma mediates antiviral activity of cytokines
      against hepatitis B virus.
AB  - Cytokines are involved in early host defense against pathogen infections. In
      particular, tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma) have
      critical functions in non-cytopathic elimination of hepatitis B virus (HBV) in
      hepatocytes. However, the molecular mechanisms and mediator molecules are largely
      unknown. Here we show that interleukin-32 (IL-32) is induced by TNF and IFN-gamma
      in hepatocytes, and inhibits the replication of HBV by acting intracellularly to
      suppress HBV transcription and replication. The gamma isoform of IL-32 (IL
      32gamma) inhibits viral enhancer activities by downregulating liver-enriched
      transcription factors. Our data are validated in both an in vivo HBV mouse model
      and primary human hepatocytes. This study thus suggests that IL-32gamma functions
      as intracellular effector in hepatocytes for suppressing HBV replication to
      implicate a possible mechanism of non-cytopathic viral clearance.

PMID- 30115932
TI  - Ocean sprawl facilitates dispersal and connectivity of protected species.
AB  - Highly connected networks generally improve resilience in complex systems. We
      present a novel application of this paradigm and investigated the potential for
      anthropogenic structures in the ocean to enhance connectivity of a protected
      species threatened by human pressures and climate change. Biophysical dispersal
      models of a protected coral species simulated potential connectivity between oil
      and gas installations across the North Sea but also metapopulation outcomes for
      naturally occurring corals downstream. Network analyses illustrated how just a
      single generation of virtual larvae released from these installations could
      create a highly connected anthropogenic system, with larvae becoming competent to
      settle over a range of natural deep-sea, shelf and fjord coral ecosystems
      including a marine protected area. These results provide the first study showing
      that a system of anthropogenic structures can have international conservation
      significance by creating ecologically connected networks and by acting as
      stepping stones for cross-border interconnection to natural populations.

PMID- 30115931
TI  - The VAR2CSA malaria protein efficiently retrieves circulating tumor cells in an
      EpCAM-independent manner.
AB  - Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is of
      high value for disease monitoring and molecular characterization. Despite the
      development of many new CTC isolation platforms in the last decade, their
      isolation and detection has remained a challenge due to the lack of specific and
      sensitive markers. In this feasibility study, we present a method for CTC
      isolation based on the specific binding of the malaria rVAR2 protein to oncofetal
      chondroitin sulfate (ofCS). We show that rVAR2 efficiently captures CTCs from
      hepatic, lung, pancreatic, and prostate carcinoma patients with minimal
      contamination of peripheral blood mononuclear cells. Expression of ofCS is
      present on epithelial and mesenchymal cancer cells and is equally preserved
      during epithelial-mesenchymal transition of cancer cells. In 25 stage I-IV
      prostate cancer patient samples, CTC enumeration significantly correlates with
      disease stage. Lastly, rVAR2 targets a larger and more diverse population of CTCs
      compared to anti-EpCAM strategies.

PMID- 30115933
TI  - Ideal Cardiovascular Health Metrics Associated with Reductions in the Risk of
      Extracranial Carotid Artery Stenosis: a Population-based Cohort Study.
AB  - The cardiovascular health (CVH) metrics are closely related to the risk of
      stroke. Extracranial carotid artery stenosis (ECAS) represents an important risk
      factor for ischemic stroke. The present study aims to explore the longitudinal
      effect of the baseline CVH metrics on the development of ECAS. Totally 5,440
      participants were randomly enrolled in the Asymptomatic Polyvascular
      Abnormalities Community study from 2010 to 2011. Information regarding the seven
      CVH metrics was collected at baseline. ECAS was assessed by performing carotid
      duplex sonography at baseline (2010-2011) and during the follow-up (2012-2013).
      Finally 3,487 subjects were included, and 976 participants developed ECAS during
      the 2-year follow-up. The optimum CVH status was associated with a 42% (95%
      confidence interval: 0.40-0.85) decreased risk of the incidence of ECAS after
      adjusting for age, sex, weight, education, income, alcohol use, waist-hip ratio,
      triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein
      cholesterol, uric acid, homocysteine, and C-reactive protein. Ideal physical
      activity, total cholesterol and fasting blood glucose were independent protective
      factors of ECAS. In this cohort study, the ideal baseline CVH status was
      negatively associated with the occurrence of ECAS during the follow-up. This
      study provides practical insight for further developing effective screening
      strategies or implementing the best medical treatment.

PMID- 30115934
TI  - Cloning, characterization and functional analysis of an Alveoline-like protein in
      the shell of Pinctada fucata.
AB  - Shell matrix proteins (SMPs) have important functions in biomineralization. In
      the past decades, the roles of SMPs were gradually revealed. In 2015, our group
      identified 72 unique SMPs in Pinctada fucata, among which Alveoline-like (Alv)
      protein was reported to have homologous genes in Pinctada maxima and Pinctada
      margaritifera. In this study, the full-length cDNA sequence of Alv and the
      functional analysis of Alv protein during shell formation were explored. The
      deduced protein (Alv), which has a molecular mass of 24.9 kDa and an isoelectric
      point of 11.34, was characterized, and the functional analyses was explored in
      vivo and in vitro. The Alv gene has high expression in mantle and could response
      to notching damage. The functional inhibition of Alv protein in vivo by injecting
      recombinant Alv (rAlv) antibodies destroyed prism structure but accelerated nacre
      growth. Western blot and immunofluorescence staining showed that native Alv
      exists in the EDTA-insoluble matrix of both prismatic and nacreous layers and has
      different distribution patterns in the inner or outer prismatic layer. Taken
      together, the characterization and functional analyses of matrix protein Alv
      could expand our understanding of basic matrix proteins and their functions
      during shell formation.

PMID- 30115935
TI  - Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on
      nuclear accumulation of p53 tumor suppressor.
AB  - Exportin-1 (XPO1) controls the nucleo-cytoplasmic trafficking of several key
      growth regulatory and tumor suppressor proteins. Nuclear export blockade through
      XPO1 inhibition is a target for therapeutic inhibition in many cancers. Studies
      have suggested XPO1 upregulation as an indicator of poor prognosis in gastric
      cancer. In the current study, we investigated the anti-tumor efficacy of
      selective inhibitors of nuclear export (SINE) compounds KPT-185, KTP-276 and
      clinical stage selinexor (KPT-330) in gastric cancer. XPO1 was found to be
      overexpressed in gastric cancer as compared to adjacent normal tissues and was
      correlated with poor survival outcomes. Among the 3 SINE compounds, in vitro
      targeting of XPO1 with selinexor resulted in greatest potency with significant
      anti-proliferative effects at nano molar concentrations. XPO1 inhibition by
      selinexor resulted in nuclear accumulation of p53, causing cell cycle arrest and
      apoptosis. Also, inhibition of XPO1 lead to the cytoplasmic retention of p21 and
      suppression of survivin. Orally administered selienxor caused significant
      inhibition of tumor growth in xenograft models of gastric cancer. Furthermore,
      combination of selinexor with irinotecan exhibited greater anti-tumor effect
      compared to individual treatment. Taken together, our study underscores the
      therapeutic utility of XPO1 targeting in gastric cancer and suggests the
      potential benefits of XPO1 inhibition in-combination with chemotherapy.

PMID- 30115936
TI  - Damage and Failure of Axonal Microtubule under Extreme High Strain Rate: An In
      Silico Molecular Dynamics Study.
AB  - As a major cytoskeleton element of the axon, the breaking of microtubules (MTs)
      has been considered as a major cause of the axon degeneration. High strain rate
      loading is considered as one of the key factors in microtubule breaking. Due to
      the small size of microtubule, the real-time behavior of microtubule breaking is
      hard to capture. This study employs fully-atomistic molecular dynamics (MD)
      simulation to determine the failure modes of microtubule under different loadings
      conditions such as, unidirectional stretching, bending and hydrostatic expansion.
      For each loading conditions, MT is subjected to extreme high strain rate (108-109
      s-1) loading. We argue that such level of high strain rate may be realized during
      cavitation bubble implosion. For each loading type, we have determined the
      critical energy for MT rupture. The associated rupture mechanisms are also
      discussed. We observed that the stretching has the lowest energy barrier to break
      the MT at the nanosecond time scale. Moreover, the breakage between the dimers
      starts at ~16% of total strain when stretched, which is much smaller compared to
      the reported strain-at-failure (50%) for lower strain rate loading. It suggests
      that MT fails at a significantly smaller strain states when loaded at higher
      strain rates.

PMID- 30115937
TI  - Directly Probing Light Absorption Enhancement of Single Hierarchical Structures
      with Engineered Surface Roughness.
AB  - Hierarchical nanostructures are ideal architectures to harvest solar energy. The
      understanding of light absorption in single hierarchical structures is emergently
      important and greatly helpful in enhancing multiscale optical phenomena and light
      management. However, due to the geometrical complexity of hierarchical
      architectures, theoretical and experimental studies of light absorption have
      faced significant challenges. Here, we directly quantify light absorption in
      single hierarchical structures for the first time by utilizing VO2-based near
      field powermeter. It is found that light trapping is significantly enhanced in
      rough microwires when the roughness amplitude is comparable to the incident light
      wavelength. The roughness enhanced light absorption is verified as a general
      phenomenon on both VO2 and Si hierarchical structures. Therefore, our work not
      only provides a simple and quantitative method of measuring light absorption upon
      single geometrically complex structures in micro/nanoscale, but also contributes
      a general rule to rationally design of hierarchical structures for enhanced
      performance in photoelectric and photochemical applications.

PMID- 30115938
TI  - Modelling vaporised hydrogen peroxide efficacy against mono-species biofilms.
AB  - This pilot study investigates a novel approach towards efficacy testing of
      antimicrobial cleaning agents; focusing primarily on hydrogen peroxide vapour
      (HPV). Contaminated surfaces are recognised modes of pathogen transmission within
      healthcare environments and increase the risk of pathogen acquisition in newly
      admitted patients. Studies have shown these pathogens can survive on surfaces for
      extended periods of time in spite of cleaning. This resilience is characteristic
      of biofilm formation and recent publications have identified their presence in
      hospitals. In this study, biofilm models comprised of multidrug-resistant
      organisms (MDROs) were generated using a drip flow reactor and exposed to HPV
      decontamination. The MDROs included Acinetobacter baumannii, Enterococcus
      faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus
      aureus. Upon exposure, samples were periodically removed and enumerated to
      generate kill curves for each species. Consequently revealing any inherent
      resistances; such as catalase-producing organisms which expressed reduced
      susceptibility. Epifluorescence microscopy revealed an abundance of viable and
      non-viable microcolonies before and after decontamination, respectively. Greater
      than 6-Log10 reduction was achieved within a 100 minutes exposure time. This
      pilot study puts forward a potential methodology for testing antimicrobial agents
      against biofilms and supports the efficacy of HPV.

PMID- 30115939
TI  - Regulation of cofilin phosphorylation in glomerular podocytes by testis specific
      kinase 1 (TESK1).
AB  - Expression of a constitutively active Rho A (V14Rho) in podocytes in vivo induces
      albuminuria and foot process (FP) effacement. These effects may be mediated by
      the Rho A effector Rho kinase (ROK); but inhibition of ROK with Y27632 failed to
      attenuate albuminuria or FP effacement in V14Rho mice. ROK activates LIM kinases
      (LIMKs), which phosphorylate and inhibit the actin depolymerizing factor cofilin
      1 (CFL1). Sustained phosphorylation of CFL1 is implicated in human nephrotic
      diseases, but Y27632 did not inhibit phosphorylation of CFL1 in vivo, despite
      effective ROK inhibition. CFL1 is also phosphorylated by testis-specific kinase 1
      (TESK1) on the same serine residue. TESK1 was expressed in podocytes, and,
      similar to the in vivo situation, Y27632 had little effect on phospho-CFL1
      (pCFL1) levels in cultured podocytes. In contrast, Y27632 reduced pCFL1 levels in
      TESK1 knockout (KO) cells. ROK inhibition enhanced podocyte motility but, the
      motility promoting effect of Y27632 was absent in TESK1 KO podocytes. Thus, TESK1
      regulates podocyte cytoskeletal dynamics in glomerular podocytes and may play an
      important role in regulating glomerular filtration barrier integrity in
      glomerular disease processes.

PMID- 30115940
TI  - Phase-coherent solitonic Josephson heat oscillator.
AB  - Since its recent foundation, phase-coherent caloritronics has sparkled continuous
      interest giving rise to numerous concrete applications. This research field deals
      with the coherent manipulation of heat currents in mesoscopic superconducting
      devices by mastering the Josephson phase difference. Here, we introduce a new
      generation of devices for fast caloritronics able to control local heat power and
      temperature through manipulation of Josephson vortices, i.e., solitons. Although
      most salient features concerning Josephson vortices in long Josephson junctions
      were comprehensively hitherto explored, little is known about soliton-sustained
      coherent thermal transport. We demonstrate that the soliton configuration
      determines the temperature profile in the junction, so that, in correspondence of
      each magnetically induced soliton, both the flowing thermal power and the
      temperature significantly enhance. Finally, we thoroughly discuss a fast
      solitonic Josephson heat oscillator, whose frequency is in tune with the
      oscillation frequency of the magnetic drive. Notably, the proposed heat
      oscillator can effectively find application as a tunable thermal source for
      nanoscale heat engines and coherent thermal machines.

PMID- 30115941
TI  - The Chinese Medicine Wu-Tou Decoction Relieves Neuropathic Pain by Inhibiting
      Hippocampal Microglia Activation.
AB  - The comorbidity between the nociceptive and mental syndromes adds to the
      refractoriness of neuropathic pain (NP). Wu-Tou decoction (WTD) has been
      prescribed for chronic pain for thousands of years in China. Recently, we
      reported that WTD was helpful for hippocampus and co-curative for the
      nociceptive, depressive and anxiety behaviors in the spinal cord ligation (SNL)
      mice. However, the mechanism underlying the rescue of hippocampus, as well as the
      roles hippocampus assumed in co-curation remain unexplored. In this study, we
      validated that in SNL mice, the long-lasting damages to limbic system were mainly
      limited to hippocampus. In addition, hippocampal neurons were proven sensitive to
      harms induced by microglia and rescued by WTD, which in sum indicated hippocampal
      microglia as the critical modulator of co-curation. To validate this hypothesis
      the hippocampal microglia were mal-activated in shamed mice, in which the atrophy
      of hippocampus and the development of NP syndromes were consolidated and proven
      rescued by WTD. On the contrary, in the SNL mice, the failure to control
      hippocampal microglia was sufficient to void all the rescues mediated by WTD. In
      sum, our study points out that the effective modulation of microglia in
      hippocampus is of pivotal importance for the co-curation by WTD.

PMID- 30115942
TI  - Rhamnogalacturonan, a chemically-defined polysaccharide, improves intestinal
      barrier function in DSS-induced colitis in mice and human Caco-2 cells.
AB  - Natural polysaccharides have emerged as an important class of bioactive compounds
      due their beneficial biological effects. Here we investigated the protective and
      healing effects of rhamnogalacturonan (RGal) isolated from Acmella oleracea (L.)
      R.K. Jansen leaves in an experimental model of intestinal inflammation in mice
      and in heterogeneous human epithelial colorectal adenocarcinoma cells (Caco-2).
      The findings demonstrated that RGal treatment for 7 days reduced the severity of
      DSS-induced colitis by protecting mice from weight loss, macroscopic damage and
      reduction of colon length. When compared to the DSS group, RGal also protected
      the colon epithelium and promoted the maintenance of mucosal enterocytes and
      mucus secreting goblet cells, in addition to conserving collagen homeostasis and
      increasing cell proliferation. In an in vitro barrier function assay, RGal
      reduced the cellular permeability after exposure to IL-1beta, while decreasing IL
      8 secretion and claudin-1 expression and preserving the distribution of occludin.
      Furthermore, we also observed that RGal accelerated the wound healing in Caco-2
      epithelial cell line. In conclusion, RGal ameliorates intestinal barrier function
      in vivo and in vitro and may represent an attractive and promising molecule for
      the therapeutic management of ulcerative colitis.

PMID- 30115943
TI  - Macroecological patterns of the phytoplankton production of polyunsaturated
      aldehydes.
AB  - The polyunsaturated aldehydes (PUAs) are bioactive metabolites commonly released
      by phytoplankton species. Based primarily on laboratory experiments, PUAs have
      been implicated in deleterious effects on herbivores and competing phytoplankton
      species or in the regulation of the rates of bacterial organic matter
      remineralization; however, the role of the PUAs at an ecosystem level is still
      under discussion. Using data of PUA production in natural phytoplankton
      assemblages over a wide range of conditions, we analyzed macroecological patterns
      aiming for a comprehensive environmental contextualization that will further our
      understanding of the control and ecologic role played by these compounds. PUA
      composition changed from the predominance of decadienal in oligotrophy,
      octadienal in eutrophy, and heptadienal at intermediate conditions. The
      production of PUAs per unit biomass also showed a strong relationship with the
      trophic status, sharply increasing towards oligotrophic conditions and with small
      sized cells reaching the highest production rates. High ratios of dissolved
      inorganic nitrogen to dissolved inorganic phosphorus also promoted PUA
      production, albeit to a considerably lesser extent. Although the allelopathic use
      of PUAs to outcompete other phytoplankton or reduce herbivory may be key in some
      environments and interactions, the macroecological patterns found here, showing
      higher production towards the poorest waters and among the small species
      typically populating these environments, support and link at the large scale the
      hypotheses of the nutrient-derived stress as driver for the production of PUAs
      together with the use of these compounds as boosters for the nutrient
      remineralization.

PMID- 30115944
TI  - The polymorphism rs35767 at IGF1 locus is associated with serum urate levels.
AB  - Previous studies suggested that the IGF-1/IGF-1 receptor signaling pathway may
      contribute to regulate uric acid levels. To confirm this hypothesis, we assessed
      the effects of the IGF-1-raising genetic variant rs35767 on urate levels in serum
      and urine, and we investigated IGF-1 ability to modulate the expression of
      transporters involved in reabsorption and secretion of uric acid in the kidney.
      The study population included 2794 adult Whites. 24-hour urinary uric acid
      concentration was available for 229 subjects. rs35767 polymorphism was screened
      using TaqMan genotyping assays. HEK293 (human embryonic kidney-293) cell line was
      treated with IGF-1 (1, 5, 10, 50 nM) for 24-hours, and differences in the
      expression of urate transporters were evaluated via Western Blot and real time
      rtPCR. Individuals carrying the IGF-1-raising allele (rs35767 T) exhibited
      significantly lower levels of serum urate according to both additive and
      recessive models, after correction for gender, age, BMI, glucose tolerance,
      glomerular filtration rate, and anti-hypertensive treatment. TT genotype carriers
      displayed higher uricosuria than C allele carriers did, after adjusting for
      confounders. Exposure of HEK293 cells to IGF-1 resulted in a dose-dependent
      increase of uric acid transporters deputed to uric acid excretion (MRP4, NPT1 and
      BCRP), and reduction of GLUT9 expression, the major mediator of uric acid
      reabsorption, both at mRNA and protein level. We observed a significant
      association between the functional polymorphism rs35767 near IGF1 with serum
      urate concentrations and we provide a mechanistic explanation supporting a causal
      role for IGF-1 in the regulation of uric acid homeostasis.

PMID- 30115945
TI  - The placebo effect in the motor domain is differently modulated by the external
      and internal focus of attention.
AB  - Among the cognitive strategies that can facilitate motor performance in sport and
      physical practice, a prominent role is played by the direction of the focus of
      attention and the placebo effect. Consistent evidence converges in indicating
      that these two cognitive functions can influence the motor outcome, although no
      study up-to-now tried to study them together in the motor domain. In this
      explorative study, we combine for the first time these approaches, by applying a
      placebo procedure to increase force and by manipulating the focus of attention
      with explicit verbal instructions. Sixty healthy volunteers were asked to perform
      abduction movements with the index finger as strongly as possible against a
      piston and attention could be directed either toward the movements of the finger
      (internal focus, IF) or toward the movements of the piston (external focus, EF).
      Participants were randomized in 4 groups: two groups underwent a placebo
      procedure (Placebo-IF and Placebo-EF), in which an inert treatment was applied on
      the finger with verbal information on its positive effects on force; two groups
      underwent a control procedure (Control-IF and Control-EF), in which the same
      treatment was applied with overt information about its inefficacy. The placebo
      groups were conditioned about the effects of the treatment with a surreptitious
      amplification of a visual feedback signalling the level of force. During the
      whole procedure, we recorded actual force, subjective variables and
      electromyography from the hand muscles. The Placebo-IF group had higher force
      levels after the procedure than before, whereas the Placebo-EF group had a
      decrease of force. Electromyography showed that the Placebo-IF group increased
      the muscle units recruitment without changing the firing rate. These findings
      show for the first time that the placebo effect in motor performance can be
      influenced by the subject's attentional focus, being enhanced with the internal
      focus of attention.

PMID- 30115946
TI  - Differential expression of serum biomarkers in hemodialysis patients with mild
      cognitive decline: A prospective single-center cohort study.
AB  - Studies suggest that hemodialysis patients are at a higher risk for cognitive
      decline than healthy individuals; however, underlying mechanisms have not been
      fully elucidated. We aimed to investigate the roles of serum biomarkers, such as
      brain-derived neurotrophic factor (BDNF), inflammatory cytokines, fibroblast
      growth factor (FGF)-23 and its co-receptor alpha-klotho and platelet (PLT) count
      in mild cognitive decline (MCD) of patients undergoing hemodialysis in this
      prospective cohort study. Serum levels of BDNF, tumour necrosis factor (TNF)
      alpha, interleukin (IL)-6 and the number of PLT were significantly altered in the
      MCD group compared with those in healthy controls (HCs) or those with normal
      cognitive function (NCF). Although serum alpha-klotho and FGF-23 levels were
      significantly altered in the MCD group, there were no statistical differences
      between the MCD and NCF groups. Serum BDNF levels and PLT counts were
      significantly correlated with cognitive test scores. Receiver operating
      characteristic (ROC) curves demonstrated that BDNF and PLT were potential
      biomarkers for improved MCD diagnosis in patients with hemodialysis. These
      findings suggest that hemodialysis-related MCD is associated with altered BDNF,
      TNF-alpha and IL-6 levels as well as PLT counts and that serum BDNF levels and
      PLT counts are potential biomarkers for hemodialysis-related MCD diagnosis.

PMID- 30115947
TI  - Multiple mechanisms contributing to ciprofloxacin resistance among Gram negative
      bacteria causing infections to cancer patients.
AB  - Fluoroquinolones have been used for prophylaxis against infections in cancer
      patients but their impact on the resistance mechanisms still require further
      investigation. To elucidate mechanisms underlying ciprofloxacin (CIP) resistance
      in Gram-negative pathogens causing infections to cancer patients, 169 isolates
      were investigated. Broth microdilution assays showed high-level CIP resistance in
      89.3% of the isolates. Target site mutations were analyzed using PCR and DNA
      sequencing in 15 selected isolates. Of them, all had gyrA mutations (codons 83
      and 87) with parC mutations (codons 80 and 84) in 93.3%. All isolates were
      screened for plasmid-mediated quinolone resistance (PMQR) genes and 56.8% of them
      were positive in this respect. Among PMQR genes, aac(6')-Ib-cr predominated
      (42.6%) while qnr genes were harbored by 32.5%. This comprised qnrS in 26.6% and
      qnrB in 6.5%. Clonality of the qnr-positive isolates using ERIC-PCR revealed that
      most of them were not clonal. CIP MIC reduction by CCCP, an efflux pump
      inhibitor, was studied and the results revealed that contribution of efflux
      activity was observed in 18.3% of the isolates. Furthermore, most fluoroquinolone
      resistance mechanisms were detected among Gram-negative isolates recovered from
      cancer patients. Target site mutations had the highest impact on CIP resistance
      as compared to PMQRs and efflux activity.

PMID- 30115948
TI  - Insight into the molecular mechanism behind PEG-mediated stabilization of
      biofluid lipases.
AB  - Bioconjugates established between anionic polyethylene glycol (PEG) based
      polymers and cationic proteins have proven to be a promising strategy to engineer
      thermostable biocatalysts. However, the enzyme activity of these bioconjugates is
      very low and the mechanism of non-covalent PEG-stabilization is yet to be
      understood. This work presents experimental and molecular dynamics simulation
      studies, using lipase-polymer surfactant nanoconjugates from mesophile Rhizomucor
      miehei (RML), performed to evaluate the effect of PEG on enzyme stability and
      activity. Results demonstrated that the number of hydrogen bonds between the
      cationized RML and PEG chain correlates with enzyme thermostability. In addition,
      an increase of both the number of PEG-polymers units and cationization degree of
      the enzyme leads to a decrease of enzyme activity. Modelling with SAXS data of
      aqueous solutions of the biofluid lipases agrees with previous hypothesis that
      these enzymes contain a core constituted of folded protein confined by a shell of
      surfactants. Together results provide valuable insight into the mechanism of non
      covalent PEG mediated protein stabilization relevant for engineering active and
      thermostable biofluids. Furthermore, the first biofluids RML with activity
      comparable to their cationized counterpart are presented.

PMID- 30115949
TI  - Pregnancy Outcomes in Women of Advanced Maternal Age: a Retrospective Cohort
      Study from China.
AB  - This retrospective cohort study attempts to investigate pregnancy complications
      and adverse pregnancy outcomes in women of advanced maternal age (AMA). Data were
      extracted from electronic medical records system at West China Second University
      Hospital of Sichuan University from January 2013 to July 2016. The study cohort
      consisted 8 subgroups of women on 4 different age levels (20-29 years, 30-34
      years, 35-39 years and >=40 years) and 2 different parities (primiparity and
      multiparity). In the study period, 38811 women gave birth at our hospital, a
      randomized block was used to include 2800 women of singleton pregnancy >28
      gestational weeks, with 350 patients in each subgroup. Maternal complications and
      fetal outcomes were collected and defined according to relevant guidelines.
      Confounding factors representing maternal demographic characteristics were
      identified from previous studies and analysed in multivariate analysis. There was
      an increasing trend for the risks of adverse pregnancy outcomes with increasing
      age, especially in AMA groups. Our study showed that AMA, primiparity, maternal
      overweight or obesity, lower educational level and residence in rural area
      increased pregnancy complications and adverse fetal outcomes. Increased
      professional care as well as public concern is warranted.

PMID- 30115950
TI  - Whole-exome sequencing reveals known and novel variants in a cohort of
      intracranial vertebral-basilar artery dissection (IVAD).
AB  - Intracranial vertebral-basilar artery dissection (IVAD) is an arterial disorder
      leading to life-threatening consequences. Genetic factors are known to be
      causative to certain syndromic forms of IVAD. However, systematic study of the
      molecular basis of sporadic and isolated IVAD is lacking. To identify genetic
      variants contributing to the etiology of IVAD, we enrolled a cohort of 44
      unrelated cases with a clinical diagnosis of isolated IVAD and performed whole
      exome sequencing (WES) for all the participants; a trio exome sequencing approach
      was used when samples from both parents were available. Four previously reported
      disease-causing heterozygous variants (three in COL3A1 and one in FBN1) and seven
      novel heterozygous variants in IVAD-related genes were identified. In addition,
      six variants in novel IVAD genes including two de novo heterozygous nonsynonymous
      variants (each in VPS52 and CDK18), two stop-gain variants (each in MYH9 and
      LYL1), and two heterozygous biallelic variants in TNXB were considered to be
      possibly contributing to the phenotype, with unknown significance according to
      the existing knowledge. A significantly higher mutational rate of IVAD candidate
      genes was observed in patients versus our in-house controls (P = 0.002) (DISCO
      study, http://www.discostudy.org/ , n = 2248). Our study provided a mutational
      landscape for patients with isolated IVAD.

PMID- 30115952
TI  - Parasite transmission between trophic levels stabilizes predator-prey
      interaction.
AB  - Manipulative parasites that promote their transmission by altering their host's
      phenotype are widespread in nature, which suggests that host manipulation allows
      the permanent coexistence of the host with the parasite. However, the underlying
      mechanism by which host manipulation affects community stability remains
      unelucidated. Here, using a mathematical model, we show that host manipulation
      can stabilise community dynamics. We consider systems wherein parasites are
      transmitted between different trophic levels: intermediate host prey and final
      host predator. Without host manipulation, the non-manipulative parasite can
      destabilise an otherwise globally stable prey-predator system, causing population
      cycles. However, host manipulation can dampen such population cycles,
      particularly when the manipulation is strong. This finding suggests that host
      manipulation is a consequence of self-organized behavior of the parasite
      populations that allows permanent coexistence with the hosts and plays a key role
      in community stability.

PMID- 30115951
TI  - Lysines and Arginines play non-redundant roles in mediating chemokine
      glycosaminoglycan interactions.
AB  - Glycosaminoglycans (GAGs) bind a large array of proteins and mediate fundamental
      and diverse roles in human physiology. Ion pair interactions between protein
      lysines/arginines and GAG sulfates/carboxylates mediate binding. Neutrophil
      activating chemokines (NAC) are GAG-binding proteins, and their sequences reveal
      high selectivity for lysines over arginines indicating they are functionally not
      equivalent. NAC binding to GAGs impacts gradient formation, receptor functions,
      and endothelial activation, which together regulate different components of
      neutrophil migration. We characterized the consequence of mutating lysine to
      arginine in NAC CXCL8, a well-characterized GAG-binding protein. We chose three
      lysines - two highly conserved lysines (K20 and K64) and a CXCL8-specific lysine
      (K67). Interestingly, the double K64R/K20R and K64R/K67R mutants are highly
      impaired in recruiting neutrophils in a mouse model. Further, both the mutants
      bind GAG heparin with higher affinity but show similar receptor activity. NMR and
      MD studies indicate that the structures are essentially identical to the WT, but
      the mutations alter the network of intramolecular ion pair interactions. These
      observations collectively indicate that the reduced in vivo recruitment is due to
      altered GAG interactions, higher GAG binding affinity can be detrimental, and
      specificity of lysines fine-tunes in vivo GAG interactions and function.

PMID- 30115953
TI  - Improving Stem Cell Delivery to the Trabecular Meshwork Using Magnetic
      Nanoparticles.
AB  - Glaucoma is a major cause of blindness and is frequently associated with elevated
      intraocular pressure. The trabecular meshwork (TM), the tissue that primarily
      regulates intraocular pressure, is known to have reduced cellularity in glaucoma.
      Thus, stem cells, if properly delivered to the TM, may offer a novel therapeutic
      option for intraocular pressure control in glaucoma patients. For this purpose,
      targeted delivery of stem cells to the TM is desired. Here, we used magnetic
      nanoparticles (Prussian blue nanocubes [PBNCs]) to label mesenchymal stem cells
      and to magnetically steer them to the TM following injection into the eye's
      anterior chamber. PBNC-labeled stem cells showed increased delivery to the TM vs.
      unlabeled cells after only 15-minute exposure to a magnetic field. Further, PBNC
      labeled mesenchymal stem cells could be delivered to the entire circumference of
      the TM, which was not possible without magnetic steering. PBNCs did not affect
      mesenchymal stem cell viability or multipotency. We conclude that this labeling
      approach allows for targeted, relatively high-efficiency delivery of stem cells
      to the TM in clinically translatable time-scales, which are necessary steps
      towards regenerative medicine therapies for control of ocular hypertension in
      glaucoma patients.

PMID- 30115954
TI  - Analysis of eIF2B bodies and their relationships with stress granules and P
      bodies.
AB  - Eukaryotic cells respond to stress and changes in the environment in part by
      repressing translation and forming cytoplasmic assemblies called stress granules
      and P-bodies, which harbor non-translating mRNAs and proteins. A third, but
      poorly understood, assembly called the eIF2B body can form and contains the eIF2B
      complex, an essential guanine exchange factor for the translation initiation
      factor eIF2. Hypomorphic EIF2B alleles can lead to Vanishing White Matter Disease
      (VWMD), a leukodystrophy that causes progressive white matter loss. An unexplored
      question is how eIF2B body formation is controlled and whether VWMD alleles in
      EIF2B alter the formation of eIF2B bodies, stress granules, or P-bodies. To
      examine these issues, we assessed eIF2B body, stress granule, and P-body
      induction in wild-type yeast cells and cells carrying VWMD alleles in the EIF2B2
      (GCD7) and EIF2B5 (GCD6) subunits of eIF2B. We demonstrate eIF2B bodies are
      rapidly and reversibly formed independently of stress granules during acute
      glucose deprivation. VWMD mutations had diverse effects on stress-induced
      assemblies with some alleles altering eIF2B bodies, and others leading to
      increased P-body formation. Moreover, some VWMD-causing mutations in GCD7 caused
      hyper-sensitivity to chronic GCN2 activation, consistent with VWMD mutations
      causing hyper-sensitivity to eIF2alpha phosphorylation and thereby impacting VWMD
      pathogenesis.

PMID- 30115955
TI  - A comparison between scalp- and source-reconstructed EEG networks.
AB  - EEG can be used to characterise functional networks using a variety of
      connectivity (FC) metrics. Unlike EEG source reconstruction, scalp analysis does
      not allow to make inferences about interacting regions, yet this latter approach
      has not been abandoned. Although the two approaches use different assumptions,
      conclusions drawn regarding the topology of the underlying networks should,
      ideally, not depend on the approach. The aim of the present work was to find an
      answer to the following questions: does scalp analysis provide a correct estimate
      of the network topology? how big are the distortions when using various pipelines
      in different experimental conditions? EEG recordings were analysed with amplitude
      and phase-based metrics, founding a strong correlation for the global
      connectivity between scalp- and source-level. In contrast, network topology was
      only weakly correlated. The strongest correlations were obtained for MST leaf
      fraction, but only for FC metrics that limit the effects of volume
      conduction/signal leakage. These findings suggest that these effects alter the
      estimated EEG network organization, limiting the interpretation of results of
      scalp analysis. Finally, this study also suggests that the use of metrics that
      address the problem of zero lag correlations may give more reliable estimates of
      the underlying network topology.

PMID- 30115956
TI  - A thyroid hormone regulated asymmetric responsive centre is correlated with eye
      migration during flatfish metamorphosis.
AB  - Flatfish metamorphosis is a unique post-embryonic developmental event in which
      thyroid hormones (THs) drive the development of symmetric pelagic larva into
      asymmetric benthic juveniles. One of the eyes migrates to join the other eye on
      the opposite side of the head. Developmental mechanisms at the basis of the
      acquisition of flatfish anatomical asymmetry remain an open question. Here we
      demonstrate that an TH responsive asymmetric centre, determined by deiodinase 2
      expression, ventrally juxtaposed to the migrating eye in sole (Solea
      senegalensis) correlates with asymmetric cranial ossification that in turn drives
      eye migration. Besides skin pigmentation that is asymmetric between dorsal and
      ventral sides, only the most anterior head region delimited by the eyes becomes
      asymmetric whereas the remainder of the head and organs therein stay symmetric.
      Sub-ocular ossification is common to all flatfish analysed to date, so we propose
      that this newly discovered mechanism is universal and is associated with eye
      migration in all flatfish.

PMID- 30115958
TI  - Hamming weight and tight constraints of multi-qubit entanglement in terms of
      unified entropy.
AB  - We establish a characterization of multi-qubit entanglement constraints in terms
      of non-negative power of entanglement measures based on unified-(q, s) entropy.
      Using the Hamming weight of the binary vector related with the distribution of
      subsystems, we establish a class of tight monogamy inequalities of multi-qubit
      entanglement based on the alphath-power of unified-(q, s) entanglement for alpha
      >= 1. For 0 <= beta <= 1, we establish a class of tight polygamy inequalities of
      multi-qubit entanglement in terms of the betath-power of unified-(q, s)
      entanglement of assistance. Thus our results characterize the monogamy and
      polygamy of multi-qubit entanglement for the full range of non-negative power of
      unified entanglement.

PMID- 30115957
TI  - Predicting postoperative facial swelling following impacted mandibular third
      molars extraction by using artificial neural networks evaluation.
AB  - Patients' postoperative facial swelling following third molars extraction may
      have both biological impacts and social impacts. The purpose of this study was to
      evaluate the accuracy of artificial neural networks in the prediction of the
      postoperative facial swelling following the impacted mandibular third molars
      extraction. The improved conjugate grads BP algorithm combining with adaptive BP
      algorithm and conjugate gradient BP algorithm together was used. In this neural
      networks model, the functional projective relationship was established among
      patient's personal factors, anatomy factors of third molars and factors of
      surgical procedure to facial swelling following impacted mandibular third molars
      extraction. This neural networks model was trained and tested based on the data
      from 400 patients, in which 300 patients were made as the training samples, and
      another100 patients were assigned as the test samples. The improved conjugate
      grads BP algorithm was able to not only avoid the problem of local minimum
      effectively, but also improve the networks training speed greatly. 5-fold cross
      validation was used to get a better sense of the predictive accuracy of the
      neural network and early stopping was used to improve generalization. The
      accuracy of this model was 98.00% for the prediction of facial swelling following
      impacted mandibular third molars extraction. This artificial intelligence model
      is approved as an accurate method for prediction of the facial swelling following
      impacted mandibular third molars extraction.

PMID- 30115959
TI  - Non-metastatic castration resistant prostate cancer: a review of current and
      emerging medical therapies.
AB  - BACKGROUND: Non-metastatic castration resistant prostate cancer (M0CRPC) is a
      heterogenous disease state affecting an estimated 100,000 men in the United
      States. Development of more sensitive modalities for detection of metastasis has
      altered the landscape of advanced prostate cancer, but M0CRPC has remained a
      condition that previously lacked FDA-approved treatment. The emerging data on new
      generation Androgen Receptor (AR) pathway inhibitors should address this gap in
      the management of such patients. METHODS: We reviewed and summarized the current
      literature for the definition, diagnosis and treatment of M0CRPC. We highlight
      the results of recent Phase III trials that show significant impact on the
      outcomes of M0CRPC. RESULTS: Androgen deprivation therapy remains the foundation
      of therapy for M0CRPC. Recently published Phase III trials provided data on
      improved progression free survival when ADT is augmented with newer AR pathway
      inhibitors. The SPARTAN trial showed that metastasis-free survival (MFS) for
      patients treated with apalutamide plus ADT is 40.5 months compared to 16.2 months
      for patients who received standard ADT plus placebo, a 72% reduction in the risk
      of distant metastasis or death in apalutamide plus ADT compared to ADT plus
      placebo. The PROSPER trial demonstrated that MFS for patients treated with
      enzalutamide plus ADT was 36.6 months compared to 14.7 months for patients who
      received standard ADT only indicating a 71% reduction in the risk of developing
      metastatic CRPC or death compared to ADT alone. The ARAMIS trial on darolutamide,
      another AR pathway inhibitor, is also ongoing, and can potentially be another
      fitting option for M0CRPC. CONCLUSION: The recent Phase III trials SPARTAN and
      PROPSER demonstrate effective treatment options for the M0CRPC disease state that
      has historically lacked treatment from high level evidence. In particular, an FDA
      approved treatment, Apalutamide, can finally be offered for M0CRPC patients. The
      newer AR pathway inhibitors should provide a basis for further investigation into
      treatments for M0CRPC.

PMID- 30115960
TI  - MRI in active surveillance: a critical review.
AB  - INTRODUCTION: Recent technological advancements and the introduction of modern
      anatomical and functional sequences have led to a growing role for
      multiparametric magnetic resonance imaging (mpMRI) in the detection, risk
      assessment and monitoring of early prostate cancer. This includes men who have
      been diagnosed with lower-risk prostate cancer and are looking at the option of
      active surveillance (AS). The purpose of this paper is to review the recent
      evidence supporting the use of mpMRI at different time points in AS, as well as
      to discuss some of its potential pitfalls. METHODS: A combination of electronic
      and manual searching methods were used to identify recent, important papers
      investigating the role of mpMRI in AS. RESULTS: The high negative predictive
      value of mpMRI can be exploited for the selection of AS candidates. In addition,
      mpMRI can be efficiently used to detect higher risk disease in patients already
      on surveillance. CONCLUSION: Although there is an ongoing debate regarding the
      precise nature of its optimal implementation, mpMRI is a promising risk
      stratification tool and should be considered for men on AS.

PMID- 30115963
TI  - Rising to the Ebola challenge, again.

PMID- 30115962
TI  - Hematoxylin and eosin staining of intact tissues via delipidation and ultrasound.
AB  - Acquiring information on the precise distribution of a tumor is essential to
      evaluate intratumoral heterogeneity. Conventional hematoxylin and eosin staining,
      which has been used by pathologists for more than 100 years, is the gold standard
      of tumor diagnosis. However, it is difficult to stain entire tumor tissues with
      hematoxylin and eosin and then acquire the three-dimensional distribution of
      cells in solid tumors due to difficulties in the staining and rinsing. In this
      paper, we propose a modified hematoxylin and eosin staining method, in which
      delipidation and ultrasound waves were applied to enhance tissue permeability and
      accelerate dye diffusion. This improved hematoxylin and eosin staining method is
      termed iHE (intact tissue hematoxylin and eosin staining). We applied the iHE
      method to stain intact organs of mice, which were then sectioned and imaged
      sequentially. The results showed that the whole tissue was stained homogeneously.
      Combined with micro-optical sectioning tomography (MOST), the iHE method can be
      used for 3D volume imaging and to evaluate the intratumoral heterogeneity of the
      entire tumor tissue spatially. Therefore, this method may help to accurately
      diagnose the invasion stage of tumors and guide clinical treatments.

PMID- 30115961
TI  - Estradiol Prevents High Glucose-Induced beta-cell Apoptosis by Decreased BTG2
      Expression.
AB  - Hyperglycemia stimulates several pathways to induce pancreatic beta-cell
      apoptosis. In our previous study by mRNA analysis, we demonstrated that B-cell
      translocation gene 2 (BTG2) expression was up-regulated in INS-1 cells cultured
      under high glucose conditions, but this effect was reversed by estrogen. In the
      present study, we demonstrated that BTG2 mRNA and protein expressions in both INS
      1 cells and mouse pancreatic islets increased under high glucose conditions
      compared to those cultured under basal glucose conditions, while in the presence
      of estrogen, the BTG2 mRNA and protein expressions decreased. SiRNA-BTG2
      significantly reduced cell apoptosis, cleaved-caspase 3, and Bax, compared to the
      siRNA-control in INS-1 cultured under high glucose conditions. We further
      demonstrated that BTG2 promoter activity was activated under high glucose
      conditions whereas estrogen significantly reduced it. The effects of estrogen on
      BTG2 expression were inhibited by estrogen receptor inhibitors. Also, under high
      glucose conditions, p53 and Bax mRNA and protein expressions increased, but they
      decreased in the presence of estrogen. Again, the effect of estrogen on p53 and
      Bax expression was inhibited by estrogen receptor inhibitors. Taken together,
      this study demonstrates that estrogen reduces pancreatic beta-cell apoptosis
      under high glucose conditions via suppression of BTG2, p53, and Bax expressions.

PMID- 30115965
TI  - Publisher Correction: Materials challenges for the Starshot lightsail.
AB  - In the version of this Perspective originally published, the titles of the
      references were missing; all versions have now been amended to include them.

PMID- 30115964
TI  - Colicin FY inhibits pathogenic Yersinia enterocolitica in mice.
AB  - Yersiniosis belongs to the common foodborne diseases around the world, and
      frequently manifests as diarrhea that can be treated with probiotics. Colicin FY
      is an antibacterial agent produced by bacteria and it is capable of specific
      growth inhibition of Yersinia enterocolitica, the causative agent of
      gastrointestinal yersiniosis. In this study, recombinant E. coli producing
      colicin FY were constructed, using both known probiotic strains EcH22 and
      EcColinfant, and the newly isolated murine strains Ec1127 and Ec1145. All E. coli
      strains producing colicin FY inhibited growth of pathogenic Y. enterocolitica
      during co-cultivation in vitro. In dysbiotic mice treated with streptomycin, E.
      coli strains producing colicin FY inhibited progression of Y. enterocolitica
      infections. This growth inhibition was not observed in mice with normal gut
      microflora, likely due to insufficient colonization capacity of E. coli strains
      and/or due to spatial differences in intestinal niches. Isogenic Y.
      enterocolitica producing colicin FY was constructed and shown to inhibit
      pathogenic Y. enterocolitica in mice with normal microflora. Evidence of in vivo
      antimicrobial activity of colicin FY may have utility in the treatment of Y.
      enterocolitica infections.

PMID- 30115966
TI  - Retrograde Transport by Clathrin-Coated Vesicles is Involved in Intracellular
      Transport of PrPSc in Persistently Prion-Infected Cells.
AB  - Intracellular dynamics of an abnormal isoform of prion protein (PrPSc) are
      tightly associated with prion propagation. However, the machineries involved in
      the intracellular trafficking of PrPSc are not fully understood. Our previous
      study suggested that PrPSc in persistently prion-infected cells dynamically
      circulates between endocytic-recycling compartments (ERCs) and peripheral regions
      of the cells. To investigate these machineries, we focused on retrograde
      transport from endosomes to the trans-Golgi network, which is one of the pathways
      involved in recycling of molecules. PrPSc was co-localized with components of
      clathrin-coated vesicles (CCVs) as well as those of the retromer complex, which
      are known as machineries for retrograde transport. Fractionation of intracellular
      compartments by density gradient centrifugation showed the presence of PrPSc and
      the components of CCVs in the same fractions. Furthermore, PrPSc was detected in
      CCVs isolated from intracellular compartments of prion-infected cells. Knockdown
      of clathrin interactor 1, which is one of the clathrin adaptor proteins involved
      in retrograde transport, did not change the amount of PrPSc, but it altered the
      distribution of PrPSc from ERCs to peripheral regions, including late
      endosomes/lysosomes. These data demonstrated that some PrPSc is transported from
      endosomes to ERCs by CCVs, which might be involved in the recycling of PrPSc.

PMID- 30115967
TI  - Exercise benefits in cardiovascular disease: beyond attenuation of traditional
      risk factors.
AB  - Despite strong scientific evidence supporting the benefits of regular exercise
      for the prevention and management of cardiovascular disease (CVD), physical
      inactivity is highly prevalent worldwide. In addition to merely changing well
      known risk factors for systemic CVD, regular exercise can also improve
      cardiovascular health through non-traditional mechanisms. Understanding the
      pathways through which exercise influences different physiological systems is
      important and might yield new therapeutic strategies to target pathophysiological
      mechanisms in CVD. This Review includes a critical discussion of how regular
      exercise can have antiatherogenic effects in the vasculature, improve autonomic
      balance (thereby reducing the risk of malignant arrhythmias), and induce
      cardioprotection against ischaemia-reperfusion injury, independent of effects on
      traditional CVD risk factors. This Review also describes how exercise promotes a
      healthy anti-inflammatory milieu (largely through the release of muscle-derived
      myokines), stimulates myocardial regeneration, and ameliorates age-related loss
      of muscle mass and strength, a frequently overlooked non-traditional CVD risk
      factor. Finally, we discuss how the benefits of exercise might also occur via
      promotion of a healthy gut microbiota. We argue, therefore, that a holistic view
      of all body systems is necessary and useful when analysing the role of exercise
      in cardiovascular health.

PMID- 30115968
TI  - Lenticulostriate vasculopathy in preterm infants: a new classification, clinical
      associations and neurodevelopmental outcome.
AB  - OBJECTIVE: To examine the inter-rater reliability for the diagnosis of LSV on
      cranial ultrasound (cUS), determine the risk factors associated with LSV and its
      progression, and examine neurodevelopmental outcome. STUDY DESIGN: Prospective
      case-control study of neonates <=32wks of gestation assessed for LSV by serial
      cUS (n = 1351) between 2012 and 2014 and their neurodevelopment at 18-36mon
      corrected age compared to controls. RESULTS: Agreement for LSV on cUS improved
      from Kappaappa 0.4-0.7 after establishing definitive criteria and guidelines. BPD
      was the only variable associated with the occurrence and the progression of LSV.
      Cytomegalovirus (CMV) infection occurred in one neonate (1.5%).
      Neurodevelopmental outcome of neonates with LSV did not differ from controls.
      CONCLUSIONS: Establishment of well-defined stages of LSV improves the reliability
      of the diagnosis and allows identification of neonates with progression of LSV.
      Although LSV was associated with BPD, it was not associated with congenital CMV
      infection.

PMID- 30115969
TI  - beta-nicotinamide mononucleotide (NMN) production in Escherichia coli.
AB  - Diabetes is a chronic and progressive disease with continuously increasing
      prevalence, rising financial pressure on the worldwide healthcare systems.
      Recently, the insulin resistance, hallmark of type 2 diabetes, was cured in mice
      treated with NAD+ precursor beta-nicotinamide mononucleotide (NMN), no toxic
      effects being reported. However, NMN has a high price tag, more cost effective
      production methods are needed. This study proposes a biotechnological NMN
      production method in Escherichia coli. We show that bicistronic expression of
      recombinant nicotinamide phosphoribosyl transferase (Nampt) and phosphoribosyl
      pyrophosphate (PRPP) synthetase in the presence of nicotinamide (NAM) and lactose
      may be a successful strategy for cost effective NMN production. Protein
      expression vectors carrying NAMPT gene from Haemophilus ducreyi and PRPP
      synthetase from Bacillus amyloliquefaciens with L135I mutation were transformed
      in Escherichia coli BL21(DE3)pLysS. NMN production reached a maximum of 15.42 mg
      per L of bacterial culture (or 17.26 mg per gram of protein) in these cells grown
      in PYA8 medium supplemented with 0.1% NAM and 1% lactose.

PMID- 30115971
TI  - Mutant NRAS Q61K is responsible for MAPK pathway activation in the MARIMO cell
      line and renders these cells independent of the CALR-MPL-JAK2-STAT5 pathway.

PMID- 30115970
TI  - Hematopoietic reconstitution of neonatal immunocompetent mice to study conditions
      with a perinatal window of susceptibility.
AB  - Efficient hematopoietic reconstitution of wild type mice requires
      preconditioning. Established experimental protocols exist to transplant
      hematopoietic stem cells into lethally irradiated or chemically myeloablated
      adult mice or unirradiated immunodeficient mice. We sought to develop a protocol
      to reconstitute immuno-replete neonatal mice. We describe irradiation and
      injection procedures for two-day old mice that lead to efficient long-term
      reconstitution of primary and secondary lymphoid organs. We demonstrate that the
      frequencies of lymphoid and myeloid cells in primary and secondary lymphoid
      organs are indistinguishable from unirradiated uninjected sex- and age-matched
      control animals by 5 weeks post-reconstitution. Thus, this system will facilitate
      studies aimed at understanding the developmental and environmental mechanisms
      that contribute to conditions that have a window of susceptibility during the
      perinatal period.

PMID- 30115972
TI  - The Prevalence of Attention Deficit/Hyperactivity Disorder among Chinese Children
      and Adolescents.
AB  - Updating the worldwide prevalence estimates of attention-deficit hyperactivity
      disorder (ADHD) has significant applications for the further study of ADHD.
      However, previous reviews included few samples of Chinese children and
      adolescents. To conduct a systematic review of ADHD prevalence in Mainland China,
      Hong Kong, and Taiwan to determine the possible causes of the varied estimates in
      Chinese samples and to offer a reference for computing the worldwide pooled
      prevalence. We searched for PubMed, Embase, PsycINFO, Web of Science, China
      National Knowledge Infrastructure, VIP, WANFANG DATA, and China Science
      Periodical Database databases with time and language restrictions. A total of 67
      studies covering 642,266 Chinese children and adolescents were included. The
      prevalence estimates of ADHD in Mainland China, Hong Kong, and Taiwan were 6.5%,
      6.4%, and 4.2%, respectively, with a pooled estimate of 6.3%. Multivariate meta
      regression analyses indicated that the year of data collection, age, and family
      socioeconomic status of the participants were significantly associated with the
      prevalence estimates. Our findings suggest that geographic location plays a
      limited role in the large variability of ADHD prevalence estimates. Instead, the
      variability may be explained primarily by the years of data collection, and
      children's socioeconomic backgrounds, and methodological characteristics of
      studies.

PMID- 30115974
TI  - Message from the new Editors-in-Chief.

PMID- 30115975
TI  - PRSS8 suppresses colorectal carcinogenesis and metastasis.
AB  - The serine protease PRSS8 has shown important physiological and pathological
      functions, but its roles in cancer initiation and progression are unclear. We
      developed and dynamically characterized a conditional knockout Prss8fl/fl, p
      Villin-Cre+ mouse model. We found that genetic deficiency of the Prss8 gene
      caused spontaneous colitis and an inflamed rectum at an early age and caused
      intestinal tumors at a late age, which were linked to increased intestinal cell
      proliferation and migration but decreased cell differentiation. Increased PRSS8
      expression inhibited cancer cell growth and metastasis in nude mice and inhibited
      cancer cell migration, invasion, colony formation and tumor sphere formation in
      vitro, but decreased PRSS8 expression facilitated malignancies in vivo and in
      vitro. Gene profiling on manipulated cancer cells and intestinal epithelial cells
      of Prss8 mouse models, gene set enrichment analysis and mechanistic studies
      revealed that PRSS8 targeted the Wnt/beta-catenin, epithelial-mesenchymal
      transition, and stem cell signaling pathways, which were further supported by the
      results from the TCGA data mining and validated by immunohistochemical staining
      on colorectal cancer tissue microarrays. In conclusion, PRSS8 is a novel tumor
      suppressor that plays critical roles in the suppression of colorectal
      carcinogenesis and metastasis.

PMID- 30115973
TI  - Loss of function of miR-342-3p results in MCT1 over-expression and contributes to
      oncogenic metabolic reprogramming in triple negative breast cancer.
AB  - Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive neoplasia
      lacking the expression of hormonal receptors and human epidermal growth factor
      receptor-2. Accumulating evidence has highlighted the importance of miRNAs
      dysregulation in the establishment of cancer programs, but the functional role of
      many miRNAs remains unclear. The description of miRNAs roles might provide novel
      strategies for treatment. In the present work, an integrated analysis of miRNA
      transcriptional landscape was performed (N = 132), identifying the significant
      down-modulation of miR-342-3p in TNBC, probably because of the aberrant activity
      of estrogen receptor, which serves as a transcription factor of the miRNA, as
      demonstrated by a siRNA-knockdown approach. The enhanced expression of miR-342-3p
      significantly decreased cell proliferation, viability and migration rates of
      diverse TN cells in vitro. Bioinformatic and functional analyses revealed that
      miR-342-3p directly targets the monocarboxylate transporter 1 (MCT1), which
      promotes lactate and glucose fluxes alteration, thus disrupting the metabolic
      homeostasis of tumor cells. Optical metabolic imaging assay defined a higher
      optical redox ratio in glycolytic cells overexpressing miR-342-3p. Furthermore,
      we found that hypoxic conditions and glucose starvation attenuate miR-342-3p
      expression, suggesting a crosstalk program between these metabolic factors.
      Consistently, miR-342-3p down-modulation is associated with an increased MCT1
      expression level and glycolytic score in human triple negative tumors. Overall,
      we described for the first time the regulatory activity of miR-342-3p on relevant
      metabolic carcinogenic pathways in TN breast cancers.

PMID- 30115976
TI  - KIFC1 regulated by miR-532-3p promotes epithelial-to-mesenchymal transition and
      metastasis of hepatocellular carcinoma via gankyrin/AKT signaling.
AB  - Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide. The
      poor survival may be due to a high proportions of tumor recurrence and
      metastasis. Kinesin family member C1 (KIFC1) is highly expressed in a variety of
      neoplasms and is a potential marker for non-small cell lung cancer or ovarian
      adenocarcinoma metastasis. Nevertheless, the role of KIFC1 in HCC metastasis
      remains obscure. We investigated this in the present study using HCC cell lines
      and clinical specimens. Our results indicated that increased levels of KIFC1 were
      associated with poor prognosis and metastasis in HCC. In addition, KIFC1 induced
      epithelial-to-mesenchymal transition (EMT) and HCC metastasis both in vitro and
      in vivo. This tumorigenic effect depended on gankyrin; inhibiting gankyrin
      activity reversed EMT via activation of protein kinase B (AKT)/Twist family BHLH
      transcription factor 1 (AKT/TWIST1). We also found that KIFC1 was directly
      regulated by the microRNA miR-532-3p, whose downregulation was associated with
      metastatic progression in HCC. These results denote that a decrease in miR-532-3p
      levels results in increased KIFC1 expression in HCC, leading to metastasis via
      activation of the gankyrin/AKT/TWIST1 signaling pathway.

PMID- 30115978
TI  - Cytosolic nucleic acid sensors of the innate immune system promote liver
      regeneration after partial hepatectomy.
AB  - Stimulation of cytosolic nucleic acid sensors of innate immunity by pathogen
      derived nucleic acids is important for antimicrobial defence, but stimulation
      through self-derived nucleic acids may contribute to autoinflammation and cancer.
      DNA sensing in the cytosol requires the stimulator of interferon genes (STING),
      while cytosolic RNA sensors use mitochondrial antiviral-signalling protein
      (MAVS). In a murine model of two-thirds hepatectomy, combined deficiency of MAVS
      and STING resulted in strongly impaired hepatocyte proliferation and delayed
      recovery of liver mass. Whereas lack of MAVS and STING did not influence
      upregulation of the G1-phase cyclins D1 and E1, it substantially reduced the
      hyperphosphorylation of retinoblastoma protein, attenuated the activation of
      cyclin-dependent kinase (CDK)-2, delayed upregulation of CDK1 and cyclins A2 and
      B1, and impaired S-phase entry of hepatocytes. Mechanistically, lack of cytosolic
      nucleic acid sensors strongly upregulated the anti-proliferative mediators TGF
      beta2 and activin A, which was associated with an increased expression of the
      cell cycle inhibitors p15 and p21. Partial hepatectomy was followed by the
      release of exosomes with abundant nucleic acid cargo, which may provide ligands
      for the MAVS and STING pathways. Together, these findings identify a previously
      unrecognised function of cytosolic nucleic acid sensors of innate immunity for
      promoting liver regeneration.

PMID- 30115977
TI  - MicroRNA-224 down-regulates Glycine N-methyltransferase gene expression in
      Hepatocellular Carcinoma.
AB  - Glycine N-methyltransferase (GNMT) is a tumor suppressor for HCC. It is down
      regulated in HCC, but the mechanism is not fully understood. MicroRNA-224 (miR
      224) acts as an onco-miR in HCC. This study is the first to investigate miR-224
      targeting the coding region of GNMT transcript. The GNMT-MT plasmid containing a
      miR-224 binding site silent mutation of the GNMT coding sequence can escape the
      suppression of miR-224 in HEK293T cells. Expression of both exogenous and
      endogenous GNMT was suppressed by miR-224, while miR-224 inhibitor enhanced GNMT
      expression. miR-224 counteracts the effects of GNMT on the reduction of cell
      proliferation and tumor growth. The levels of miR-224 and GNMT mRNA showed a
      significant inverse relationship in tumor specimens from HCC patients. Utilizing
      CCl4-treated hepatoma cells and mice as a cell damage of inflammatory or liver
      injury model, we observed that the decreased expression levels of GNMT were
      accompanied with the elevated expression levels of miR-224 in hepatoma cells and
      mouse liver. Finally, hepatic AAV-mediated GNMT also reduced CCl4-induced miR-224
      expression and liver fibrosis. These results indicated that AAV-mediated GNMT has
      potential liver protection activity. miR-224 can target the GNMT mRNA coding
      sequence and plays an important role in GNMT suppression during liver
      tumorigenesis.

PMID- 30115979
TI  - Long-term bat abundance in sagebrush steppe.
AB  - Bats of western North America face many threats, but little is known about
      current population changes in these mammals. We compiled 283 surveys from 49
      hibernacula over 32 years to investigate population changes of Townsend's big
      eared bats (Corynorhinus townsendii townsendii) and western small-footed myotis
      (Myotis ciliolabrum) in Idaho, USA. This area comprises some of the best bat
      habitat in the western USA, but is threatened by land-use change. Bats in this
      area also face invasion by the pathogen causing white-nose syndrome. Little is
      known about long-term trends of abundance of these two species. In our study,
      estimated population changes for Townsend's big-eared bats varied by management
      area, with relative abundance increasing by 186% and 326% in two management
      areas, but decreasing 55% in another. For western small-footed myotis, analysis
      of estimated population trend was complicated by an increase in detection of 141%
      over winter. After accounting for differences in detection, this species declined
      region-wide by 63% to winter of 1998-1999. The population fully recovered by 2013
      2014, likely because 12 of 23 of its hibernacula were closed to public access
      from 1994 to 1998. Our data clarify long-term population patterns of two bat
      species of conservation concern, and provide important baseline understanding of
      western small-footed myotis prior to the arrival of white-nose syndrome in this
      area.

PMID- 30115980
TI  - Novel phages of healthy skin metaviromes from South Africa.
AB  - Recent skin metagenomic studies have investigated the harbored viral diversity
      and its possible influence on healthy skin microbial populations, and tried to
      establish global patterns of skin-phage evolution. However, the detail associated
      with the phages that potentially play a role in skin health has not been
      investigated. While skin metagenome and -metavirome studies have indicated that
      the skin virome is highly site specific and shows marked interpersonal variation,
      they have not assessed the presence/absence of individual phages. Here, we took a
      semi-culture independent approach (metaviromic) to better understand the
      composition of phage communities on skin from South African study participants.
      Our data set adds over 130 new phage species of the skin to existing databases.
      We demonstrated that identical phages were present on different individuals and
      in different body sites, and we conducted a detailed analysis of the structural
      organization of these phages. We further found that a bacteriophage related to
      the Staphylococcus capitis phage Stb20 may be a common skin commensal virus
      potentially regulating its host and its activities on the skin.

PMID- 30115981
TI  - 3D microfluidic in vitro model and bioinformatics integration to study the
      effects of Spatholobi Caulis tannin in cervical cancer.
AB  - Cervical cancer is considered the fourth most common malignant disease in women.
      Recently, tannin from Spatholobi Caulis (TTS) has been shown to have potent
      anticancer and antiproliferative characteristics in a few preliminary studies.
      This experiment used 3D microfluidic, flow cytometry, and gene chip technology to
      study the efficacy and mechanism of action of TTS, as well as molecular docking
      technology to study the effect of drugs on related proteins. The cell survival
      rates of the five groups measured by the 3D microfluidic chip were 94%, 85%, 64%,
      55%, and 42%, respectively. With the increase in drug concentration, the cell
      survival rate gradually decreased. Apoptosis rates detected in the five groups
      were 2.12%, 15.87%, 33.40%, 41.13%, and 55.10%, respectively. These data suggest
      that TTS can promote cell apoptosis. The percentages of cells in the G0/G1 phase
      were 43.39%, 55.07%, 59.57%, 64.56%, and 67.39% in the five groups, respectively.
      TTS was demonstrated to inhibit the conversion of cells from G0/G1 to S phase and
      G2/M phase and inhibit gene and protein synthesis to block cell proliferation.
      TTS can effectively modulate pathogenic proteins. The results confirmed the
      efficacy of TTS against HeLa cells and that TTS can be used as an adjunct in
      cervical cancer prevention and treatment.

PMID- 30115982
TI  - Gold nanoparticles-induced cytotoxicity in triple negative breast cancer involves
      different epigenetic alterations depending upon the surface charge.
AB  - Gold nanoparticles (AuNPs) are used enormously in different cancers but very
      little is known regarding their molecular mechanism and surface charge role in
      the process of cell death. Here, we elucidate the molecular mechanism by which
      differentially charged AuNPs induce cytotoxicity in triple negative breast cancer
      (TNBC) cells. Cytotoxicity assay revealed that both negatively charged (citrate
      capped) and positively charged (cysteamine-capped) AuNPs induced cell-death in a
      dose-dependent manner. We provide first evidence that AuNPs-induced oxidative
      stress alters Wnt signalling pathway in MDA-MB-231 and MDA-MB-468 cells. Although
      both differentially charged AuNPs induced cell death, the rate and mechanism
      involved in the process of cell death were different. Negatively charged AuNPs
      increased the expression of MKP-1, dephosphorylated and deacetylated histone H3
      at Ser10 and K9/K14 residues respectively whereas, positively charged AuNPs
      decreased the expression of MKP-1, phosphorylated and acetylated histone H3 at
      Ser 10 and K9/K14 residues respectively. High-resolution transmission electron
      microscopy (HRTEM) studies revealed that AuNPs were localised in cytoplasm and
      mitochondria of MDA-MB-231 cells. Interestingly, AuNPs treatment makes MDA-MB-231
      cells sensitive to 5-fluorouracil (5-FU) by decreasing the expression of
      thymidylate synthetase enzyme. This study highlights the role of surface charge
      (independent of size) in the mechanisms of toxicity and cell death.

PMID- 30115983
TI  - Metabolic syndrome status over 2 years predicts incident chronic kidney disease
      in mid-life adults: a 10-year prospective cohort study.
AB  - We investigated whether changes in MetS status over two years modify the 10-year
      risk of CKD and proteinuria. A prospective cohort study was conducted in 7,251
      subjects without CKD at baseline. We categorized subjects according to MetS
      status over two years: non-MetS (no MetS at either visit), intermittent MetS
      (positive for MetS at one assessment), and persistent MetS (positive for MetS at
      two assessments). The hazard ratio (HR) of new-onset CKD over 10-year was
      calculated using Cox models. During the 10-year follow-up period, 923 (12.7%)
      developed CKD. Compared to the non-MetS group, the fully adjusted HR for new
      onset CKD was the highest in the persistent MetS group (HR, 1.53; 95% CI, 1.23
      1.90), followed by the intermittent MetS group (HR, 1.29; 95% CI, 1.04-1.59) (P
      for trend <0.001). The HR for developing proteinuria was 1.79 (95% CI, 1.15-2.79)
      in the persistent MetS group and 0.70 (95% CI, 0.42-1.19) in the intermittent
      MetS group when the non-MetS group was considered as the reference group.
      Temporal changes in MetS status over two years influenced the 10-year risk of
      incident CKD and proteinuria. Our findings suggest that monitoring and strictly
      controlling MetS are important in preventing renal function decline.

PMID- 30115984
TI  - Using spectral-domain optical coherence tomography to evaluate the type and
      thickness of interdigitation zone band in adult Chinese.
AB  - To study types and thickness of interdigitation zone band in adult Chinese
      subjects, we conducted a cross-sectional study. The population-based Beijing Eye
      Study 2011 included 3468 individuals with a mean age of 64.6 +/- 9.8 years. 263
      people (263eyes) with a mean age of 64.8 years were randomly selected cases
      without macular diseases included in the study. A detailed ophthalmic examination
      was performed including SD-OCT for measurement of the thickness of
      interdigitation zone band. There are two types of interdigitation zone band; the
      type1 which can distinguish RPE-BM complex in 170 eyes; and the Type 2 which the
      two layers merged involved 93 eyes. In type1, the mean thickness of the
      interdigitation zone band was significantly thicker in the foveal center (16.46
      +/- 2.92 MUm), then nasal macular region (16.19 +/- 2.69 MUm), temporal macular
      region (15.73 +/- 2.68 . MUm), superior region (15.72 +/- 2.70 MUm), and inferior
      macular region (14.84 +/- 2.63 MUm) (P all < 0.05). And the mean thickness of the
      interdigitation zone band in the foveal center associated with the subfoveal
      choroidal thickness (P = 0.025) and level of education (P = 0.033). The increase
      in the thickness of the interdigitation zone band may play a role in the
      pathophysiologic features of various age-related ocular conditions.

PMID- 30115985
TI  - Exploring multiple effects of Zn0.15Mg0.85O nanoparticles on Bacillus subtilis
      and macrophages.
AB  - The increasing number of multidrug resistant bacteria raises a serious public
      health concern, which is exacerbated by the lack of new antibiotics. Metal oxide
      nanoparticles are already applied as an antibacterial additive in various
      products used in everyday life but their modes of action have remained unclear.
      Moreover, their potential negative effects to human health are still under
      evaluation. We explored effects of mixed metal oxide Zn0.15Mg0.85O on Bacillus
      subtilis, as a model bacterial organism, and on murine macrophages. Zn0.15Mg0.85O
      killed planktonic bacterial cells and prevented biofilm formation by causing
      membrane damages, oxidative stress and metal ions release. When exposed to a sub
      inhibitory amount of Zn0.15Mg0.85O, B. subtilis up-regulates proteins involved in
      metal ions export, oxidative stress response and maintain of redox homeostasis.
      Moreover, expression profiles of proteins associated with information processing,
      metabolism, cell envelope and cell division were prominently changed. Multimode
      of action of Zn0.15Mg0.85O suggests that no single strategy may provide bacterial
      resistance. Macrophages tolerated Zn0.15Mg0.85O to some extend by both the
      primary phagocytosis of nanoparticles and the secondary phagocytosis of damaged
      cells. Bacterial co-treatment with ciprofloxacin and non-toxic amount of
      Zn0.15Mg0.85O increased antibiotic activity towards B. subtilis and E. coli.

PMID- 30115986
TI  - Prevalence of Transmitted HIV drug resistance in antiretroviral treatment naive
      newly diagnosed individuals in China.
AB  - To investigate the prevalence and temporal trend of transmitted drug resistance
      (TDR), a nationwide cross-sectional survey was conducted among 5627 ART naive
      newly diagnosed HIV-infected individuals in 2015 in China. Totally 4704 partial
      pol sequences were obtained. Among them, the most common HIV-1 circulating
      recombinant form (CRF) or subtype was CRF01_AE (39.0%), followed by CRF07_BC
      (35.6%), CRF08_BC (8.9%), and subtype B (5.5%). TDR mutations were found in 3.6%
      of the cases, with 1.1% harboring TDR to protease inhibitors (PIs), 1.3% having
      TDR to nucleoside reverse transcriptase inhibitors (NRTIs), and 1.6% to non
      nucleoside reverse transcriptase inhibitors (NNRTIs). No significant difference
      was found in the prevalence of TDR, as compared with the results of another
      nationwide survey performed among ART naive HIV-infected people in between 2004
      and 2005, except in the 16-25 year-old group. In addition, four drug-resistant
      transmission clusters were identified in phylogenetic trees, accounting for 6.2%
      (9/145) of the individuals with TDR. Although the rate of TDR remained relatively
      low in the past 10 years in China, surveillance is still needed to monitor the
      trend of TDR and to optimize the first-line regimens.

PMID- 30115987
TI  - Author Correction: The properties of fibreboard based on
      nanolignocelluloses/CaCO3/PMMA composite synthesized through mechano-chemical
      method.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30115988
TI  - Flexible memristive devices based on polyimide:mica nanosheet nanocomposites with
      an embedded PEDOT:PSS layer.
AB  - Flexible memristive devices with a structure of Al/polyimide:mica/poly(3,4
      ethylenedioxythiophene) polystyrene sulfonate/indium-tin-oxide/polyethylene
      glycol naphthalate showed electrical bistability characteristics. The maximum
      current margin of the devices with mica nanosheets was much larger than that of
      the devices without mica nanosheets. For these devices, the current vs. time
      curves showed nonvolatile characteristics with a retention time of more than 1 *
      104 s, and the current vs. number-of-cycles curves demonstrated an endurance for
      high resistance state/low resistance state switchings of 1 * 102 cycles. As to
      the operation performance, the "reset" voltage was distributed between 2.5 and 3
      V, and the "set" voltage was distributed between -0.7 and -0.5 V, indicative of
      high uniformity. The electrical characteristics of the devices after full
      bendings with various radii of curvature were similar to those before bending,
      which was indicative of devices having ultra-flexibility. The carrier transport
      and the operation mechanisms of the devices were explained based on the current
      vs. voltage curves and the energy band diagrams.

PMID- 30115989
TI  - Primary prevention of atherosclerosis by pretreatment of low-density lipoprotein
      receptor knockout mice with sesame oil and its aqueous components.
AB  - Pharmacological intervention using statins and PCSK9 inhibitors have become first
      line therapy in the prevention of hypercholesterolemia and atherosclerosis.
      Currently, no agent is available for the primary prevention of atherosclerosis.
      However, there is an emerging hypothesis that atherosclerosis could be driven by
      inflammation. In this study, we tested whether pretreatment with an aqueous
      extract from sesame oil (SOAE), which showed potent anti-inflammatory properties
      without hypocholesterolemic actions, would prevent subsequent atherosclerosis
      development in a mouse model. RAW 264.7 macrophages and female low-density
      lipoprotein receptor knockout (LDLR-/-) mice were used for in vitro and in vivo
      studies, respectively. Plasma lipids, cytokines and atherosclerotic lesions were
      quantified at the end of the study. RNA was extracted from the liver and aortic
      tissues and used for gene analysis. Pre-treatment of SOAE prevented Ox-LDL uptake
      by RAW macrophages and further inflammation in vitro. SOAE pre-treatment
      significantly reduced atherosclerotic lesions and pro-inflammatory gene
      expressions in LDLR-/- mice as compared to control mice. No significant change in
      plasma cholesterol levels was observed. A significant reduction in plasma levels
      of TNF-alpha, IL-6, MCP-1 and VCAM1 was observed in the SOAE pre-treated animals.
      This is the first study that demonstrates that pre-treatment with anti
      inflammatory agents, could delay/decrease atherosclerosis.

PMID- 30115990
TI  - In vivo imaging of bacterial colonization of the lower respiratory tract in a
      baboon model of Bordetella pertussis infection and transmission.
AB  - Recent whooping cough (pertussis) outbreaks in many countries highlight the
      crucial need for a better understanding of the pathogenesis of Bordetella
      pertussis infection of the respiratory tract. The baboon is a recently described
      preclinical model for the study of B. pertussis infection and may be ideal for
      the evaluation of new pertussis vaccines. However, many pathophysiological
      aspects, including bacterial localization and interactions, have yet to be
      described in this model. Here, we used a baboon model of infection with a
      fluorescent GFP-expressing B. pertussis strain, derived from European clinical
      isolate B1917. Juvenile baboons were used to evaluate susceptibility to infection
      and transmission. Non-invasive in vivo imaging procedures, using probe-based
      confocal endomicroscopy coupled with bronchoscopy, were developed to track
      fluorescent bacterial localization and cellular interactions with host cells in
      the lower respiratory tract of infected animals. All B1917-GFP-challenged animals
      developed classical pertussis symptoms, including paroxysmal cough,
      nasopharyngeal colonization, and leukocytosis. In vivo co-localization with
      antigen presenting cells and progressive bacterial colonization of the lower
      airways were also assessed by imaging during the first weeks of infection. Our
      results demonstrate that in vivo imaging can be used to assess bacterial
      colonization and to point out interactions in a baboon model of pertussis.

PMID- 30115991
TI  - Author Correction: Prediction of Treatment Response for Combined Chemo- and
      Radiation Therapy for Non-Small Cell Lung Cancer Patients Using a Bio
      Mathematical Model.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30115992
TI  - IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis
      infection by live attenuated BPZE1 vaccine.
AB  - BPZE1 is a live attenuated Bordetella pertussis vaccine for nasal administration
      to mimic the natural route of infection. Here, we studied the mechanism of BPZE1
      induced immunity in the murine nasal cavity in contrast to acellular vaccine
      (aPV), although both vaccines protected against lung colonization. Transfer of
      splenocytes or serum from BPZE1-vaccinated or aPV-vaccinated mice protected naive
      mice against lung colonization but not against nasal colonization. However,
      transfer of nasal washes from BPZE1-vaccinated mice resulted in protection
      against nasal colonization, which was lost in IgA-deficient or poly-Ig receptor
      deficient mice, indicating that it depends on secretory IgA (SIgA) induction
      induced in the nose. BPZE1-induced protection against nasal colonization was long
      lived despite the relatively rapid decay of SIgA, indicating a potent BPZE1
      induced local memory response, likely due to CD4+ tissue-resident memory T cells
      induced in the nose by BPZE1. These cells produced interleukin-17 (IL-17), known
      to be important for SIgA secretion. Furthermore, BPZE1 failed to protect Il17-/-
      mice against nasal colonization by B. pertussis and induced only background
      levels of nasal SIgA. Thus, our results show important differences in the
      protective mechanism between the upper and the lower murine respiratory tract and
      demonstrate an IL-17-dependent SIgA-mediated mechanism of BPZE1-induced
      protection against B. pertussis nasopharyngeal colonization.

PMID- 30115993
TI  - Natural killer T cells mediate inflammation in the bile ducts.
AB  - Cholangiocytes function as antigen-presenting cells with CD1d-dependent
      activation of natural killer T (NKT) cells in vitro. NKT cells may act both pro-
      and anti-inflammatory in liver immunopathology. We explored this immune pathway
      and the antigen-presenting potential of NKT cells in the bile ducts by
      challenging wild-type and Cd1d-/- mice with intrabiliary injection of the NKT
      cell activating agent oxazolone. Pharmacological blocking of CD1d-mediated
      activation was performed with a monoclonal antibody. Intrabiliary oxazolone
      injection in wild-type mice caused acute cholangitis with significant weight
      loss, elevated serum levels of alanine transaminase, aspartate transaminase,
      alkaline phosphatase and bilirubin, increased histologic grade of cholangitis and
      number of T cells, macrophages, neutrophils and myofibroblasts per portal tract
      after 7 days. NKT cells were activated after intrabiliary injection of oxazolone
      with upregulation of activation markers. Cd1d-/- and wild-type mice pretreated
      with antibody blocking of CD1d were protected from disease. These findings
      implicate that cells in the bile ducts function as antigen-presenting cells in
      vivo and activate NKT cells in a CD1d-restricted manner. The elucidation of this
      biliary immune pathway opens up for potentially new therapeutic approaches for
      cholangiopathies.

PMID- 30115994
TI  - Polyclonal HIV envelope-specific breast milk antibodies limit founder SHIV
      acquisition and cell-associated virus loads in infant rhesus monkeys.
AB  - Breast milk HIV-1 transmission is currently the predominant contributor to
      pediatric HIV infections. Yet, only ~10% of breastfeeding infants born to
      untreated HIV-infected mothers become infected. This study assessed the
      protective capacity of natural HIV envelope-specific antibodies isolated from the
      milk of HIV-infected women in an infant rhesus monkey (RM), tier 2 SHIV oral
      challenge model. To mimic placental and milk maternal antibody transfer, infant
      RMs were i.v. infused and orally treated at the time of challenge with a single
      weakly neutralizing milk monoclonal antibody (mAb), a tri-mAb cocktail with
      weakly neutralizing and ADCC functionalities, or an anti-influenza control mAb.
      Of these groups, the fewest tri-mAb-treated infants had SHIV detectable in plasma
      or tissues (2/6, 5/6, and 7/8 animals infected in tri-mAb, single-mAb, and
      control-mAb groups, respectively). Tri-mAb-treated infants demonstrated
      significantly fewer plasma transmitted/founder variants and reduced peripheral
      CD4+ T cell proviral loads at 8 weeks post-challenge compared to control mAb
      treated infants. Abortive infection was observed as detectable CD4+ T cell
      provirus in non-viremic control mAb- and single mAb-, but not in tri-mAb-treated
      animals. These results suggest that polyfunctional milk antibodies contribute to
      the natural inefficiency of HIV-1 transmission through breastfeeding and infant
      vaccinations eliciting non-neutralizing antibody responses could reduce postnatal
      HIV transmission.

PMID- 30115995
TI  - Desmoglein 2, but not desmocollin 2, protects intestinal epithelia from injury.
AB  - Desmosomes are the least understood intercellular junctions in the intestinal
      epithelia and provide cell-cell adhesion via the cadherins desmoglein (Dsg)2 and
      desmocollin (Dsc)2. We studied these cadherins in Crohn's disease (CD) patients
      and in newly generated conditional villin-Cre DSG2 and DSC2 knockout mice
      (DSG2DeltaIEC; DSC2DeltaIEC). CD patients exhibited altered desmosomes and
      reduced Dsg2/Dsc2 levels. The intestines of both transgenic animal lines were
      histopathologically inconspicuous. However, DSG2DeltaIEC, but not DSC2DeltaIEC
      mice displayed an increased intestinal permeability, a wider desmosomal space as
      well as alterations in desmosomal and tight junction components. After dextran
      sodium sulfate (DSS) treatment and Citrobacter rodentium exposure, DSG2DeltaIEC
      mice developed a more-pronounced colitis, an enhanced intestinal epithelial
      barrier disruption, leading to a stronger inflammation and activation of
      epithelial pSTAT3 signaling. No susceptibility to DSS-induced intestinal injury
      was noted in DSC2DeltaIEC animals. Dsg2 interacted with the cytoprotective
      chaperone Hsp70. Accordingly, DSG2DeltaIEC mice had lower Hsp70 levels in the
      plasma membrane compartment, whereas DSC2DeltaIEC mice displayed a compensatory
      recruitment of galectin 3, a junction-tightening protein. Our results demonstrate
      that Dsg2, but not Dsc2 is required for the integrity of the intestinal
      epithelial barrier in vivo.

PMID- 30115996
TI  - Pulmonary immunization with a recombinant influenza A virus vaccine induces lung
      resident CD4+ memory T cells that are associated with protection against
      tuberculosis.
AB  - The lung is the primary site of infection with the major human pathogen,
      Mycobacterium tuberculosis. Effective vaccines against M. tuberculosis must
      stimulate memory T cells to provide early protection in the lung. Recently,
      tissue-resident memory T cells (TRM) were found to be phenotypically and
      transcriptional distinct from circulating memory T cells. Here, we identified M.
      tuberculosis-specific CD4+ T cells induced by recombinant influenza A viruses
      (rIAV) vaccines expressing M. tuberculosis peptides that persisted in the lung
      parenchyma with the phenotypic and transcriptional characteristics of TRMs. To
      determine if these rIAV-induced CD4+ TRM were protective independent of
      circulating memory T cells, mice previously immunized with the rIAV vaccine were
      treated with the sphingosine-1-phosphate receptor modulator, FTY720, prior to and
      during the first 17 days of M. tuberculosis challenge. This markedly reduced
      circulating T cells, but had no effect on the frequency of M. tuberculosis
      specific CD4+ TRMs in the lung parenchyma or their cytokine response to
      infection. Importantly, mice immunized with the rIAV vaccine were protected
      against M. tuberculosis infection even when circulating T cells were profoundly
      depleted by the treatment. Therefore, pulmonary immunization with the rIAV
      vaccine stimulates lung-resident CD4+ memory T cells that are associated with
      early protection against tuberculosis infection.

PMID- 30115999
TI  - Osteopontin protects against lung injury caused by extracellular histones.
AB  - Extracellular histones are present in the airways because of cell death occurring
      during inflammation. They promote inflammation and cause tissue damage due to
      their cationic nature. The anionic phosphoglycoprotein osteopontin (OPN) is
      expressed at high levels during airway inflammation and has been ascribed both
      pro- and anti-inflammatory roles. In this study, it was hypothesized that OPN may
      neutralize the harmful activities of extracellular histones at the airway mucosal
      surface. In a model of histone-induced acute lung injury, OPN-/- mice showed
      increased inflammation and tissue injury, and succumbed within 24 h, whereas wild
      type mice showed lower degrees of inflammation and no mortality. In
      lipopolysaccharide-induced acute lung injury, wild-type mice showed less
      inflammation and tissue injury than OPN-/- mice. In bronchoalveolar lavage fluid
      from ARDS patients, high levels of OPN and also histone-OPN complexes were
      detected. In addition, OPN bound to histones with high affinity in vitro,
      resulting in less cytotoxicity and reduced formation of tissue-damaging
      neutrophil extracellular traps (NETs). The interaction between OPN and histones
      was dependent on posttranslational modification of OPN, i.e., phosphorylation.
      The findings demonstrate a novel role for OPN, modulating the pro-inflammatory
      and cytotoxic properties of free histones.

PMID- 30115997
TI  - A novel role for C-C motif chemokine receptor 2 during infection with
      hypervirulent Mycobacterium tuberculosis.
AB  - C-C motif chemokine receptor 2 (CCR2) is a major chemokine axis that recruits
      myeloid cells including monocytes and macrophages. Thus far, CCR2-/- mice have
      not been found to be susceptible to infection with Mycobacterium tuberculosis
      (Mtb). Here, using a prototype W-Beijing family lineage 2 Mtb strain, HN878, we
      show that CCR2-/- mice exhibit increased susceptibility to tuberculosis (TB).
      Following exposure to Mtb HN878, alveolar macrophages (AMs) are amongst the
      earliest cells infected. We show that AMs accumulate early in the airways
      following infection and express CCR2. During disease progression, CCR2-expressing
      AMs exit the airways and localize within the TB granulomas. RNA-sequencing of
      sorted airway and non-airway AMs from infected mice show distinct gene expression
      profiles, suggesting that upon exit from airways and localization within
      granulomas, AMs become classically activated. The absence of CCR2+ cells
      specifically at the time of AM egress from the airways resulted in enhanced
      susceptibility to Mtb infection. Furthermore, infection with an Mtb HN878 mutant
      lacking phenolic glycolipid (PGL) expression still resulted in increased
      susceptibility in CCR2-/- mice. Together, these data show a novel role for CCR2
      in protective immunity against clinically relevant Mtb infections.

PMID- 30115998
TI  - Tuning of human MAIT cell activation by commensal bacteria species and MR1
      dependent T-cell presentation.
AB  - Human mucosal-associated invariant T (MAIT) cell receptors (TCRs) recognize
      bacterial riboflavin pathway metabolites through the MHC class 1-related molecule
      MR1. However, it is unclear whether MAIT cells discriminate between many species
      of the human microbiota. To address this, we developed an in vitro functional
      assay through human T cells engineered for MAIT-TCRs (eMAIT-TCRs) stimulated by
      MR1-expressing antigen-presenting cells (APCs). We then screened 47 microbiota
      associated bacterial species from different phyla for their eMAIT-TCR stimulatory
      capacities. Only bacterial species that encoded the riboflavin pathway were
      stimulatory for MAIT-TCRs. Most species that were high stimulators belonged to
      Bacteroidetes and Proteobacteria phyla, whereas low/non-stimulator species were
      primarily Actinobacteria or Firmicutes. Activation of MAIT cells by high- vs low
      stimulating bacteria also correlated with the level of riboflavin they secreted
      or after bacterial infection of macrophages. Remarkably, we found that human T
      cell subsets can also present riboflavin metabolites to MAIT cells in a MR1
      restricted fashion. This T-T cell-mediated signaling also induced IFNgamma, TNF
      and granzyme B from MAIT cells, albeit at lower level than professional APC.
      These findings suggest that MAIT cells can discriminate and categorize complex
      human microbiota through computation of TCR signals depending on antigen load and
      presenting cells, and fine-tune their functional responses.

PMID- 30116000
TI  - Sphingosine 1-phosphate receptor modulator ONO-4641 stimulates CD11b+Gr-1+ cell
      expansion and inhibits lymphocyte infiltration in the lungs to ameliorate murine
      pulmonary emphysema.
AB  - Sphingolipids play a pivotal role in the pathogenesis of chronic obstructive
      pulmonary disease (COPD). However, little is known about the precise roles of
      sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, and its
      receptor modulation in COPD. In this study, we demonstrated that the S1P receptor
      modulator ONO-4641 induced the expansion of lung CD11b+Gr-1+ cells and
      lymphocytopenia in naive mice. ONO-4641-expanded CD11b+Gr-1+ cells showed higher
      arginase-1 activity, decreased T cell proliferation, and lower IFN-gamma
      production in CD3+ T cells, similar to the features of myeloid-derived suppressor
      cells. ONO-4641 treatment decreased airspace enlargement in elastase-induced and
      cigarette smoke-induced emphysema models and attenuated emphysema exacerbation
      induced by post-elastase pneumococcal infection, which was also associated with
      an increased number of lung CD11b+Gr-1+ cells. Adoptive transfer of ONO-4641
      expanded CD11b+Gr-1+ cells protected against elastase-induced emphysema.
      Lymphocytopenia observed in these models likely contributed to beneficial ONO
      4641 effects. Thus, ONO-4641 attenuated murine pulmonary emphysema by expanding
      lung CD11b+Gr-1+ cell populations and inducing lymphocytopenia. The S1P receptor
      might be a promising target for strategies aimed at ameliorating pulmonary
      emphysema progression.

PMID- 30116001
TI  - An essential role for the nuclear protein Akirin2 in mouse limb interdigital
      tissue regression.
AB  - The regulation of interdigital tissue regression requires the interplay of
      multiple spatiotemporally-controlled morphogen gradients to ensure proper limb
      formation and release of individual digits. Disruption to this process can lead
      to a number of limb abnormalities, including syndactyly. Akirins are highly
      conserved nuclear proteins that are known to interact with chromatin remodelling
      machinery at gene enhancers. In mammals, the analogue Akirin2 is essential for
      embryonic development and critical for a wide variety of roles in immune
      function, meiosis, myogenesis and brain development. Here we report a critical
      role for Akirin2 in the regulation of interdigital tissue regression in the mouse
      limb. Knockout of Akirin2 in limb epithelium leads to a loss of interdigital cell
      death and an increase in cell proliferation, resulting in retention of the
      interdigital web and soft-tissue syndactyly. This is associated with perdurance
      of Fgf8 expression in the ectoderm overlying the interdigital space. Our study
      supports a mechanism whereby Akirin2 is required for the downregulation of Fgf8
      from the apical ectodermal ridge (AER) during limb development, and implies its
      requirement in signalling between interdigital mesenchymal cells and the AER.

PMID- 30116002
TI  - The human metabolic profile reflects macro- and micronutrient intake distinctly
      according to fasting time.
AB  - Although the impact of dietary patterns on human serum metabolites has been
      examined, the fasting effect on the metabolic profile has not yet been
      considered. The aim of this cross-sectional study is to investigate the influence
      of fasting regarding the association between dietary patterns, reflected by macro
      and micronutrient intake, and human serum metabolites in a population-based
      cohort. A total 1197 non-diabetic German adults aged 45 to 83 years, who
      participated in baseline of the CARLA study 2002-2006 and had metabolite
      quantification were selected for this study. Macro- and micronutrient intakes
      were estimated from a food frequency questionnaire (FFQ). Concentrations of 134
      serum metabolites were measured by targeted metabolomics AbsoluteIDQ p150 Kit.
      The association of dietary patterns with serum metabolites was calculated by
      means of linear regression and the influence of the fasting status was considered
      by including interaction terms with each macro- and micronutrient. Higher self
      reported intake of alcohol and lower self-reported intake of organic acids were
      associated with higher concentrations of acylcarnitines and phosphatidylcholines.
      Mainly the associations between dietary patterns and acylcarnitines and hexose
      were altered after including interaction terms, suggesting effect modification by
      fasting status. No effect from fasting time was seen for amino acids and
      saturated, mono- and polyunsaturated phosphatidylcholines.

PMID- 30116005
TI  - Studying tumour-specific T cell responses in 3D.

PMID- 30116003
TI  - Investigation of the anti-TB potential of selected propolis constituents using a
      molecular docking approach.
AB  - Human tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading
      bacterial killer disease worldwide and new anti-TB drugs are urgently needed.
      Natural remedies have long played an important role in medicine and continue to
      provide some inspiring templates for drug design. Propolis, a substance naturally
      produced by bees upon collection of plant resins, is used in folk medicine for
      its beneficial anti-TB activity. In this study, we used a molecular docking
      approach to investigate the interactions between selected propolis constituents
      and four 'druggable' proteins involved in vital physiological functions in M.
      tuberculosis, namely MtPanK, MtDprE1, MtPknB and MtKasA. The docking score for
      ligands towards each protein was calculated to estimate the binding free energy,
      with the best docking score (lowest energy value) indicating the highest
      predicted ligand/protein affinity. Specific interactions were also explored to
      understand the nature of intermolecular bonds between the most active ligands and
      the protein binding site residues. The lignan (+)-sesamin displayed the best
      docking score towards MtDprE1 (-10.7 kcal/mol) while the prenylated flavonoid
      isonymphaeol D docked strongly with MtKasA (-9.7 kcal/mol). Both compounds showed
      docking scores superior to the control inhibitors and represent potentially
      interesting scaffolds for further in vitro biological evaluation and anti-TB drug
      design.

PMID- 30116006
TI  - High-dose ondansetron reduces activation of interoceptive and sensorimotor brain
      regions.
AB  - Several psychiatric disorders involve abnormalities of interoception and
      associated neural circuitry centered on the insula. The development of
      interventions modulating interoceptive circuits could lead to novel treatment
      approaches for these disorders. The 5-HT3 receptor antagonist ondansetron is a
      good candidate for the modulation of interoceptive circuits, as 5-HT3 receptors
      are located abundantly on sensory pathways and ondansetron has shown some
      clinical utility in disorders characterized by sensory and interoceptive
      abnormalities. The present study tested the ability of three different doses of
      ondansetron to engage neural regions involved in interoception to determine the
      drug's utility as a therapeutic agent to target circuit abnormalities in
      patients. Fifty-three healthy subjects were randomized to receive a single 8-mg
      (n = 18), 16-mg (n = 17), or 24-mg (n = 18) dose of ondansetron and placebo
      before MRI scanning on separate days. Subjects performed an fMRI task previously
      shown to engage interoceptive circuitry in which they viewed videos depicting
      body movements/sensation and control videos. The results revealed a highly
      significant relationship between dosage and activation in bilateral insula,
      somatosensory and premotor regions, cingulate cortex, and temporal cortex for
      control but not body-focused videos. These effects were driven by a robust
      reduction in activation for ondansetron compared to placebo for the 24-mg group,
      with weaker effects for the 16-mg and 8-mg groups. In conclusion, high-dose
      ondansetron reduces activation of several areas important for interoception,
      including insula and sensorimotor cortical regions. This study reveals the
      potential utility of this drug in modulating hyperactivity in these regions in
      patients.

PMID- 30116004
TI  - The Facile Modification of Polyacrylate Emulsion via Hexadecane to Enhance
      Controlled-release Profiles of Coated Urea.
AB  - Development of controlled-release urea (CRU) has attracted research attention
      because of food scarcity problems and environmental concerns. To slow down the
      nutrient release of CRU coated with waterborne polyacrylate, conventional
      emulsion polymerization (CEP), conventional emulsion polymerization containing
      hexadecane (CEP + HD), and miniemulsion polymerization (MP) were carried out to
      discern the influence of polymerization technique and hexadecane on the
      properties of emulsions, films, and on the resultant nutrient release profiles of
      controlled-release urea. The addition of hexadecane improved water resistance,
      decreased the glass-transition temperature, and slowed down the nutrient release.
      CEP + HD was superior to MP in retarding nutrient release since the majority of
      HD was distributed in the exteriors of the particles of the former and interiors
      of the particles of the latter. Exterior HD improved water resistance more
      effectively, while interior HD reduced glass-transition temperature more
      significantly. Overall, our findings showed that incorporation of HD into
      polyacrylate emulsion produces excellent coatings that delay the release of urea.
      It has great potential application in controlled-release fertilizers coated with
      waterborne polymers.

PMID- 30116007
TI  - Influence of fatty deposits in the levator aponeurosis/levator palpebrae
      superioris muscle on outcomes of aponeurotic repair in a Japanese population.
AB  - PURPOSE: To examine a part of the levator aponeurosis/levator palpebrae
      superioris (LPS) muscle that did not have fatty deposits in patients with
      aponeurotic blepharoptosis. We also analysed the relation between this length and
      surgical outcome after transcutaneous aponeurotic repair. METHODS: We measured
      the vertical length from the distal end of the anterior layer of the levator
      aponeurosis to the most distal point of fatty deposits in the levator
      aponeurosis/LPS muscle (non-fatty-deposit length) in 94 eyelids. Surgical success
      was defined as a postoperative margin reflex distance-1 (MRD-1) of 2.0-5.0 mm at
      3 months postoperatively. The eyelids were classified into two groups: a surgical
      success group (group A, 76 eyelids) and an undercorrected group (group B, 18
      eyelids). Group A was subdivided according to the evidence of a fatty deposit
      (group A1, fat present, 70 eyelids; group A2, fat absent, 6 eyelids). RESULTS:
      The non-fatty-deposit measurement was significantly longer in group A1 than in
      group B (p = 0.035). The levator aponeurosis was less advanced in groups A1 and
      A2 than in group B (both, p < 0.001), and the eyelids in groups A1 and A2
      obtained a higher MRD-1 than those in group B (both, p < 0.001). CONCLUSIONS:
      Eyelids with less fat deposit required less advancement of the levator
      aponeurosis and obtained more favourable surgical results. Intraoperative
      findings of eyelids with and without fatty deposits and measuring the non-fatty
      deposit length may be useful predictive parameters for outcomes of transcutaneous
      aponeurotic repair.

PMID- 30116008
TI  - Vitrectomy with scleral buckling versus with inferior retinectomy in treating
      primary rhegmatogenous retinal detachment with PVR and inferior breaks.
AB  - PURPOSE: To evaluate anatomic and functional outcomes of patients treated with
      pars plana vitrectomy (PPV) with scleral buckling versus PPV with inferior
      retinectomy for treatment of cases of primary rhegmatogenous retinal detachment
      (RRD) associated with proliferative vitreoretinopathy (PVR) and inferior retinal
      breaks. METHODS: Retrospective, comparative, interventional, single-center study.
      Fifty-one eyes of fifty-one patients with primary RRD associated with inferior
      breaks and PVR grade C1 or more were reviewed over 3 years. Twenty-one eyes
      underwent PPV with encircling band 360 degrees  and thirty eyes underwent PPV
      with primary inferior retinectomy. The primary outcome was final anatomic
      success. Secondary outcomes included change in visual acuity, primary anatomical
      success, the mean number of operations, and incidence of postoperative
      complications. RESULTS: Primary anatomical success of 85.7% was achieved in
      buckle group compared to 83.3% in retinectomy group (p = 0.82). Mean duration of
      follow-up and mean number of operations was 9.8 +/- 2.26 and 9.97 +/- 2.44
      months; 1.24 +/- 0.62 and 1.3 +/- 0.75 in buckle group and retinectomy group,
      respectively, achieving final anatomical success of 95.2% for the buckle group
      and 90% for the retinectomy group with no statistical significant difference (p =
      0.49). Although visual acuity (logMAR) was better in the buckle group in the 1st
      month, it became nearly equal thereafter during the follow-up period (p = 0.5).
      CONCLUSION: Similar anatomical and functional outcomes were achieved by combining
      PPV with scleral buckle or inferior retinectomy for treatment of primary RRD with
      PVR and inferior breaks.

PMID- 30116009
TI  - Impact of the Reticular Stress and Unfolded Protein Response on the inflammatory
      response in endometrial stromal cells.
AB  - During decidualization, endometrial stromal cells undergo reticular stress (RS)
      and unfolded protein response (UPR), allowing the endoplasmic reticulum-expansion
      and immunomodulators production. Physiological RS generates the activation of
      sensing proteins, inflammasome activation and mature-IL-1beta secretion,
      associated with pro-implantatory effects. We focus on the impact of RS and UPR on
      decidualized cells and whether they induce a physiological sterile inflammatory
      response through IL-1beta production. Human endometrial stromal cell line (HESC)
      after decidualization treatment with MPA + dibutyryl-cAMP (Dec) increased the
      expression of RS-sensors (ATF6, PERK and IRE1alpha) and UPR markers (sXBP1 and
      CHOP) in comparison with Non-dec cells. Then we found increased NLRP3 expression
      in Dec cells compared with Non-dec cells. In fact STF-083010 (an IRE1alpha
      inhibitor) prevented this increase. Downstream, increased levels of active
      caspase-1 on Dec cells were detected by FAM-Flica Caspase-1 associated with an
      increase in IL-1beta production. Moreover, the treatment with STF-083010
      decreased the invasion index observed in Dec cells, evaluated by an in vitro
      model of implantation. In endometrial biopsies from recurrent spontaneous
      abortion patients an increased expression of IRE1alpha was found in comparison
      with fertile women; while recurrent implantation failure samples showed a lower
      expression of sXBP1, TXNIP and NLRP3 than fertile women, suggesting that RS/UPR
      tenors might condition endometrial receptivity.

PMID- 30116010
TI  - HbA1c Measured in the First Trimester of Pregnancy and the Association with
      Gestational Diabetes.
AB  - We aimed to examine the prospective association between first trimester HbA1c and
      gestational diabetes (GDM) and explore the utility of HbA1c for prediction of
      GDM. We used data from a case-control study within the prospective NICHD Fetal
      Growth Studies-Singleton Cohort (2009-2013), which enrolled 2,802 women at 12
      U.S. clinical centers. HbA1c was measured in GDM cases (n = 107) and matched
      controls (n = 214) targeted at 8-13, 16-22, 24-29, and 34-37 gestational weeks.
      We excluded women with HbA1c >= 6.5% (48 mmol/mol) at enrollment (n = 3) or who
      had a hemoglobin variant (n = 6). At 8-13 gestational weeks, women who later
      developed GDM had significantly higher HbA1c (5.3[standard deviation 0.3]%;
      34[4]mmol/mol) than women without GDM (5.1[0.3]%; 32[3] mmol/mol) (P <= 0.001);
      this difference remained significant throughout pregnancy. Each 0.1% (1 mmol/mol)
      HbA1c increase at 8-13 weeks was associated with an adjusted 22% increased GDM
      risk (95% confidence interval 1.09-1.36). First trimester HbA1c significantly
      improved GDM prediction over conventional risk factors (AUC 0.59 vs 0.65; P =
      0.04). In conclusion, women who develop GDM may have impaired glucose homeostasis
      early in or prior to pregnancy, as indicated by their elevated first trimester
      HbA1c. First trimester HbA1c may aid in early identification of at risk women.

PMID- 30116011
TI  - Author Correction: Structural and functional studies on Pseudomonas aeruginosa
      DspI: implications for its role in DSF biosynthesis.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30116012
TI  - Effect of MBOAT7 variant on hepatitis B and C infections in Moroccan patients.
AB  - The outcomes of HBV and HCV infections are associated both with viral and host
      genetic factors. Here, we explore the role of a genetic variation located in
      membrane-bound O-acyltransferase domain-containing protein 7 (MBOAT7) gene on
      spontaneous clearance of HBV and HCV infections and on liver fibrosis. We
      genotyped MBOAT7 rs641738 polymorphism in 971 consecutive Moroccan subjects,
      including 288 patients with chronic hepatitis C (CHC), 98 cases with spontaneous
      clearance of HCV, 268 patients with chronic hepatitis B (CHB), 126 spontaneously
      cleared HBV infections and 191 healthy controls. MBOAT7 rs641738 variant is not
      associated with spontaneous clearance of HBV (OR = 0.67, 95% CI: 0.39-1.14; p =
      0.131) and HCV infections (OR = 1.33, 95% CI: 0.79-2.23; p = 0.278). Furthermore,
      multivariable logistic regression analysis adjusted for biologically relevant
      covariates and potential confounders associated with the risk of liver disease
      progression revealed that MBOAT7 rs641738 is not associated either with fibrosis
      progression in CHC group (OR = 1.12; 95% CI: 0.55-2.28; p = 0.761) or with
      chronic progressive state in CHB patients (OR = 0.81; 95% CI: 0.41-1.61; p =
      0.547). We conclude that the variant MBOAT7 rs641738 genotype is not associated
      with spontaneous clearance of HBV and HCV infections or with the progression of
      liver disease in chronic hepatitis B or C in a genetic context of Mediterranean
      patients.

PMID- 30116013
TI  - Extramedullary relapses of acute leukemias after allogeneic hematopoietic stem
      cell transplantation: clinical features, cumulative incidence, and risk factors.
AB  - The aim of this study was to evaluate extramedullary (EM) relapses and its
      features in an allogeneic hematopoietic stem cell transplantation (alloHSCT)
      cohort, which consisted of patients with acute leukemia and advanced-phase
      chronic myeloid leukemia. One hundred and twenty-eight alloHSCT patients
      transplanted between the years 2001 and 2014 were analyzed. EM relapses observed
      in acute lymphoblastic leukemia (ALL) were more frequent than that of in acute
      myeloid leukemia (AML) and CML, although calculation of cumulative risk
      incidence, BM relapse, EM relapse, and non-relapse mortality were considered as
      competing risks of each other. At the 60th month, estimated CBMR and CEMR
      incidences were, respectively, 14.3 (5.1)% and 25.9 (6.6)% in ALL, 25.8 (5.9)%
      and 15.5 (4.8)% in AML, and 61.5 (16.5)% and 17.9 (13.4)% in CML. Among multiple
      parameters, the only type of conditioning regimen (p:0.046), EM involvement at
      diagnosis (p:0.009), and the presence of GVHD were found to be associated with EM
      relapse risk independently (p:0.045). Chronic GVHD and TBI-based regimens
      significantly decreased the EM relapse risk, whereas it was higher with Mel/Flu
      and its variants. In conclusion, EM relapse is not uncommon after alloHSCT. GVHD
      and TBI-based regimens may prevent this complication.

PMID- 30116014
TI  - Comparable outcomes using propylene glycol-free melphalan for autologous stem
      cell transplantation in multiple myeloma.
AB  - Autologous stem cell transplantation (ASCT) remains a mainstay in the treatment
      of multiple myeloma (MM). While the procedure is generally safe, toxicities
      associated with high-dose melphalan conditioning are common and significantly
      affect patient quality of life. Recently, a propylene glycol-free melphalan
      formulation (PG-free MEL; Evomela(r)) was approved by the United States Food and
      Drug Administration as an ASCT-conditioning regimen for MM. PG-free MEL is more
      soluble and stable than propylene glycol-solubilized melphalan (PG-solubilized
      MEL; Alkeran(r)). As such, there is speculation that it could decrease toxicities
      and increase the efficacy of ASCT. We compared the outcomes of patients
      conditioned with PG-free MEL (n = 216) to PG-solubilized MEL (n = 200) at our
      institution. The baseline characteristics were similar between the two groups.
      After Day +0, there were no differences in terms of hospitalizations, neutropenic
      fevers, intravenous granisetron requirement, World Health Organization grade >= 2
      oral/esophageal mucositis, intravenous fluid requirement, or narcotic
      requirement. However, PG-free MEL patients had a higher incidence of diarrhea,
      which was mostly C. difficile-negative (82% vs. 71%, P = 0.015*). Day + 100
      hematologic responses and progression-free survival after ASCT were comparable.
      In summary, we demonstrate that switching to PG-free MEL did not significantly
      reduce short-term complications of ASCT or improve outcomes in MM.

PMID- 30116015
TI  - Resolving the diagnostic dilemma of T-cell clonal expansion after hematopoietic
      stem cell transplantation in T-cell lymphoma patients by TCR-gamma next
      generation sequencing.

PMID- 30116016
TI  - alphabeta T-cell-depleted haploidentical hematopoietic cell transplantation and
      zoledronate/interleukin-2 therapy in children with relapsed, high-risk
      neuroblastoma.

PMID- 30116017
TI  - Safety of mogamulizumab for relapsed ATL after allogeneic hematopoietic cell
      transplantation.

PMID- 30116018
TI  - Methods and role of minimal residual disease after stem cell transplantation.
AB  - Relapse is the major cause of treatment failure after stem cell transplantation.
      Despite the fact that relapses occurred even if transplantation was performed in
      complete remission, it is obvious that minimal residual disease is present though
      not morphologically evident. Since adaptive immunotherapy by donor lymphocyte
      infusion or other novel cell therapies as well as less toxic drugs, which can be
      used after transplantation, the detection of minimal residual disease (MRD) has
      become a clinical important variable for outcome. Besides the increasing options
      to treat MRD, the most advanced technologies currently allow to detect residual
      malignant cells with a sensitivity of 10-5 to 10-6.Under the patronage of the
      European Society for Blood and Marrow Transplantation (EBMT) and the American
      Society for Blood and Marrow Transplantation (ASBMT) the 3rd workshop was held on
      4/5 November 2016 in Hamburg/Germany, with the aim to present an up-to-date
      status of epidemiology and biology of relapse and to summarize the currently
      available options to prevent and treat post-transplant relapse. Here the current
      methods and role of minimal residual disease for myeloid and lymphoid
      malignancies are summarized.

PMID- 30116019
TI  - Graft-versus-leukaemia effect post fludarabine, melphalan and alemtuzumab reduced
      intensity allogeneic stem cell transplantat in HIV-infected patient with acute
      myeloid leukaemia.
AB  - Allogeneic stem cell transplantation (Allo-HSCT) is sine qua non to cure high
      risk acute myeloid leukaemia (AML). In spite the advent of highly active
      antiretroviral treatment, HIV-infected patients display a remarkable risk for
      haematological neoplasms such as non-Hodgkin lymphomas, Hodgkin lymphoma and
      acute leukaemia. Several case series have confirmed the efficacy of the
      autologous stem cell transplantation for the treatment of non-Hodgkin lymphomas
      in the HIV setting. Nonetheless, there is a paucity of data for the role of the
      Allo-HSCT in HIV-infected individuals with haematological malignancies. Herein,
      we presented the successful long-term outcome of a HIV-infected patient who
      received reduced intensity conditioned, matched unrelated donor transplant with
      alemtuzumab as graft-versus-host disease prophylaxis for therapy-related acute
      myeloid leukaemia. We propose that Allo-HSCT in HIV patients is safe and that
      alemtuzumab-based conditioning could further work to eradicate HIV in those whose
      donor is not CCR5 homozygous.

PMID- 30116020
TI  - Cancer in wildlife: patterns of emergence.
AB  - Cancer is ubiquitous in wildlife, affecting animals from bivalves to pachyderms
      and cetaceans. Reports of increasing frequency demonstrate that neoplasia is
      associated with substantial mortality in wildlife species. Anthropogenic
      activities and global weather changes are shaping new geographical limitations
      for many species, and alterations in living niches are associated with visible
      examples of genetic bottlenecks, toxin exposures, oncogenic pathogens, stress and
      immunosuppression, which can all contribute to cancers in wild species. Nations
      that devote resources to monitoring the health of wildlife often do so for human
      centric reasons, including for the prediction of the potential for zoonotic
      disease, shared contaminants, chemicals and medications, and for observing the
      effect of exposure from crowding and loss of habitat. Given the increasing human
      footprint on land and in the sea, wildlife conservation should also become a more
      important motivating factor. Greater attention to the patterns of the emergence
      of wildlife cancer is imperative because growing numbers of species are existing
      at the interface between humans and the environment, making wildlife sentinels
      for both animal and human health. Therefore, monitoring wildlife cancers could
      offer interesting and novel insights into potentially unique non-age-related
      mechanisms of carcinogenesis across species.

PMID- 30116021
TI  - Isolation and differential transcriptome of vascular smooth muscle cells and mid
      capillary pericytes from the rat brain.
AB  - Brain mural cells form a heterogeneous family which significantly contributes to
      the maintenance of the blood-brain barrier and regulation of the cerebral blood
      flow. Current procedures to isolate them cannot specifically separate their
      distinct subtypes, in particular vascular smooth muscle cells (VSMCs) and mid
      capillary pericytes (mcPCs), which differ among others by their expression of
      smooth muscle actin (SMA). We herein describe an innovative method allowing SMA+
      VSMCs and SMA- mcPCs to be freshly isolated from the rat cerebral cortex. Using
      differential RNA-Seq analysis, we then reveal the specific gene expression
      profile of each subtype. Our results refine the current description of the role
      of VSMCs in parenchymal cortical arterioles at the molecular level and provide a
      unique platform to identify the molecular mechanisms underlying the specific
      functions of mcPCs in the brain vasculature.

PMID- 30116022
TI  - Increased Expression of Musashi-1 Evidences Mesenchymal Repair in Maxillary Sinus
      Floor Elevation.
AB  - This study aimed to analyze the expression of Musashi-1 (MSI1) in maxillary
      native bone and grafted bone after maxillary sinus floor elevation. To do so,
      fifty-seven bone biopsies from 45 participants were studied. Eighteen samples
      were collected from native bone while 39 were obtained 6 months after maxillary
      sinus grafting procedures. Musashi-1 was analyzed by immunohistochemistry and RT
      PCR. MSI1 was detected in osteoblasts and osteocytes in 97.4% (38/39) of grafted
      areas. In native bone, MSI1 was detected in only 66.6% (12/18) of the biopsies,
      mainly in osteocytes. Detection of MSI1 was significantly higher in
      osteoprogenitor mesenchymal cells of grafted biopsies (p < 0.001) but minor in
      smooth muscle and endothelial cells; no expression was detected in adipocytes.
      The mesenchymal cells of the non-mineralized tissue of native bone showed very
      low nuclear expression of MSI1, in comparison to fusiform cells in grafted areas
      (0.28(0.13) vs. 2.10(0.14), respectively; p < 0.001). Additionally, the detection
      of MSI1 mRNA was significantly higher in biopsies from grafted areas than those
      from native bone (1.00(0.51) vs. 60.34(35.2), respectively; p = 0.029). Thus, our
      results regardig the significantly higher detection of Musashi-1 in grafted sites
      than in native bone reflects its importance in the remodeling/repair events that
      occur after maxillary sinus floor elevation in humans.

PMID- 30116023
TI  - Coplanar-gate ZnO nanowire field emitter arrays with enhanced gate-control
      performance using a ring-shaped cathode.
AB  - Nanowire field emitters have great potential for use as large-area gated field
      emitter arrays (FEAs). However, the micrometer-scale cathode patterns in gated
      FEA devices will reduce regulation of the gate voltage and limit the field
      emission currents of these devices as a result of field-screening effect among
      the neighboring nanowires. In this article, a ring-shaped ZnO nanowire pad is
      proposed to overcome this problem. Diode measurements show that the prepared ring
      shaped ZnO nanowire pad arrays shows uniform emission with a turn-on field of 5.9
      V/um and a field emission current density of 4.6 mA/cm2 under an applied field of
      9 V/um. The ZnO nanowire pad arrays were integrated into coplanar-gate FEAs and
      enhanced gate-controlled device characteristics were obtained. The gate
      controlled capability was studied via microscopic in-situ measurements of the
      field emission from the ZnO nanowires in the coplanar-gate FEAs. Based on the
      results of both simulations and experiments, we attributed the enhanced gate
      controlled device capabilities to more efficient emission of electrons from the
      ZnO nanowires as a result of the increase edge area by designing ring-shaped ZnO
      nanowire pad. The results are important to the realization of large-area gate
      controlled FEAs based on nanowire emitters for use in vacuum electronic devices.

PMID- 30116024
TI  - A prospective phase II study of pre-operative chemotherapy then short-course
      radiotherapy for high risk rectal cancer: COPERNICUS.
AB  - BACKGROUND: Neoadjuvant chemotherapy (NAC) allows earlier treatment of rectal
      cancer micro-metastases but is not standard of care. There are currently no
      biomarkers predicting long-term progression-free survival (PFS) benefit from NAC.
      PATIENTS AND METHODS: In this single arm phase II trial, patients with non
      metastatic magnetic resonance imaging (MRI)-defined operable rectal
      adenocarcinoma at high risk of post-operative metastatic recurrence, received 8
      weeks of oxaliplatin/fluorouracil NAC then short-course preoperative radiotherapy
      (SCPRT) before immediate surgery. Sixteen weeks of post-operative adjuvant
      chemotherapy (AC) was planned. A pelvic MRI was performed at week 9 immediately
      post-NAC, before SCPRT. The primary end point was feasibility assessed by
      completion of protocol treatment up to and including surgery. Secondary endpoints
      included compliance, toxicity, downstaging efficacy, and PFS. RESULTS: In total
      60 patients were recruited May 2012-June 2014. In total 57 patients completed
      protocol treatment, meeting the primary endpoint. Compliance with NAC was much
      better than AC: Comparing NAC vs. AC, the median percentage dose intensity for
      fluoropyrimidine was 100% vs. 63% and for oxaliplatin 100% vs. 45%. Treatment
      related toxicity was acceptable with no treatment-related deaths. Post-NAC MRI
      showed 44 tumours (73%) were T-downstaged and 22 (37%) had excellent MRI tumour
      regression grade (mrTRG 1-2). Median follow-up was 27 months with 2-year PFS of
      86.2% (10 events). On exploratory analysis, post-NAC mrTRG predicted PFS with no
      event among those with excellent regression. CONCLUSION: The regimen was well
      tolerated with effective downstaging and encouraging PFS. mrTRG response to NAC
      may be a new prognostic factor for long-term PFS, but needs validation in larger
      studies.

PMID- 30116025
TI  - Proteomic phenotyping of metastatic melanoma reveals putative signatures of MEK
      inhibitor response and prognosis.
AB  - BACKGROUND: Genotyping of melanomas is used to identify patients for treatment
      with BRAF and MEK inhibitors, but clinical responses are highly variable. This
      study investigated the utility of protein expression phenotyping to provide an
      integrated assessment of gene expression programs in BRAF/NRAS melanoma which
      would be useful for prognosis and may predict response to MEK inhibition.
      METHODS: Mass spectrometry profiling of early passage cell lines established from
      Stage III cutaneous melanomas was conducted. Basal protein expression was
      correlated with in vitro response to the MEK inhibitor, selumetinib. Protein
      expression in a cohort of 32 drug naive BRAF/NRAS metastatic melanoma specimens
      was examined. The prognostic utility of a subset of these proteins and mRNA
      transcripts from a separate cohort was determined. RESULTS: Unsupervised analysis
      of basal cell line protein abundances delineated response to selumetinib, but
      BRAF/NRAS genotype did not. Resistance was associated with functions including
      cell motility, cell adhesion and cytoskeletal organization. Several of these
      response biomarkers were observed in lymph node biospecimens and correlated with
      melanoma-specific survival. Loss of ICAM-1 protein and mRNA expression was a
      strong prognosticator of diminished survival in BRAF/NRAS mutant melanoma.
      CONCLUSIONS: These results demonstrate the utility of proteomic phenotyping to
      identify both putative biomarkers of response to MEK inhibition and
      prognostication associated with metastatic melanoma.

PMID- 30116026
TI  - Prognostic role of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte
      ratio in patients with bone metastases.
AB  - BACKGROUND: Skeletal metastases are a common problem in patients with cancer, and
      surgical decision making depends on multiple factors including life expectancy.
      Identification of new prognostic factors can improve survival estimation and
      guide healthcare providers in surgical decision making. In this study, we aim to
      determine the prognostic value of neutrophil/lymphocyte ratio (NLR) and
      platelet/lymphocyte ratio (PLR) in patients with bone metastasis. METHODS: One
      thousand and twelve patients from two tertiary referral centers between 2002 and
      2014 met the inclusion criteria. Bivariate and multivariate Cox regression
      analyses were performed to determine the association of NLR and PLR with
      survival. RESULTS: At 3 months, 84.0% of the patients with low NLR were alive
      versus 61.3% of the patients with a high NLR (p < 0.001), and 75.8% of the
      patients with a low PLR were alive versus 55.6% of the patients with a high PLR
      (p < 0.001). Both elevated NLR and elevated PLR were independently associated
      with worse survival (hazard ratio (HR): 1.311; 95% confidence interval (CI):
      1.117-1.538; p = 0.001) and (HR: 1.358; 95% CI: 1.152-1.601; p < 0.001),
      respectively. CONCLUSION: This study showed both NLR and PLR to be independently
      associated with survival in patients who were treated for skeletal metastasis.

PMID- 30116027
TI  - Activation of the mGlu1 metabotropic glutamate receptor has antipsychotic-like
      effects and is required for efficacy of M4 muscarinic receptor allosteric
      modulators.
AB  - Recent clinical and preclinical studies suggest that selective activators of the
      M4 muscarinic acetylcholine receptor have potential as a novel treatment for
      schizophrenia. M4 activation inhibits striatal dopamine release by mobilizing
      endocannabinoids, providing a mechanism for local effects on dopamine signaling
      in the striatum but not in extrastriatal areas. G protein-coupled receptors
      (GPCRs) typically induce endocannabinoid release through activation of Galphaq/11
      type G proteins whereas M4 transduction occurs through Galphai/o-type G proteins.
      We now report that the ability of M4 to inhibit dopamine release and induce
      antipsychotic-like effects in animal models is dependent on co-activation of the
      Galphaq/11-coupled mGlu1 subtype of metabotropic glutamate (mGlu) receptor. This
      is especially interesting in light of recent findings that multiple loss of
      function single nucleotide polymorphisms (SNPs) in the human gene encoding mGlu1
      (GRM1) are associated with schizophrenia, and points to GRM1/mGlu1 as a gene
      within the "druggable genome" that could be targeted for the treatment of
      schizophrenia. Herein, we report that potentiation of mGlu1 signaling following
      thalamo-striatal stimulation is sufficient to inhibit striatal dopamine release,
      and that a novel mGlu1 positive allosteric modulator (PAM) exerts robust
      antipsychotic-like effects through an endocannabinoid-dependent mechanism.
      However, unlike M4, mGlu1 does not directly inhibit dopamine D1 receptor
      signaling and does not reduce motivational responding. Taken together, these
      findings highlight a novel mechanism of cross talk between mGlu1 and M4 and
      demonstrate that highly selective mGlu1 PAMs may provide a novel strategy for the
      treatment of positive symptoms associated with schizophrenia.

PMID- 30116029
TI  - Association of anxiety with subcortical amyloidosis in cognitively normal older
      adults.
AB  - Late-life anxiety has been associated with increased progression from normal
      cognition to amnestic MCI, suggesting that anxiety may be a neuropsychiatric
      symptom of Alzheimer's disease (AD) pathological changes and a possible marker of
      anatomical progression in preclinical AD. This study examined whether cortical or
      subcortical amyloidosis, indicating earlier or later stages of preclinical AD,
      was associated with greater self-reported anxiety among 118 cognitively normal
      volunteers, aged 65-90 years, and whether this association was stronger in
      APOEepsilon4 carriers. Participants underwent Pittsburgh Compound B Positron
      Emission Tomography (PiB-PET) to assess fibrillar amyloid-beta burden in cortical
      and subcortical regions, and measurement of anxiety using the Hospital Anxiety
      and Depression Scale-anxiety subscale. Higher PiB-PET measures in the subcortex
      (striatum, amygdala, and thalamus), but not in the cortex, were associated with
      greater anxiety, adjusting for demographics, cognition, and depression. Findings
      were similar using a cortico-striatal staging system and continuous PET
      measurements. Anxiety was highest in APOEepsilon4 carriers with subcortical
      amyloidosis. This work supports in vivo staging of amyloid-beta deposition in
      both cortical and subcortical regions as a promising approach to the study of
      neuropsychiatric symptoms such as anxiety in cognitively normal older
      individuals. Elevated anxiety symptoms in combination with high-risk biological
      factors such as APOEepsilon4 and subcortical amyloid-beta may identify
      participants closest to MCI for secondary prevention trials.

PMID- 30116030
TI  - What if .... the Moon provides zeitgeber signals to humans?

PMID- 30116028
TI  - Identification of ADHD risk genes in extended pedigrees by combining linkage
      analysis and whole-exome sequencing.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental
      disorder with a complex genetic background, hampering identification of
      underlying genetic risk factors. We hypothesized that combining linkage analysis
      and whole-exome sequencing (WES) in multi-generation pedigrees with multiple
      affected individuals can point toward novel ADHD genes. Three families with
      multiple ADHD-affected members (Ntotal = 70) and apparent dominant inheritance
      pattern were included in this study. Genotyping was performed in 37 family
      members, and WES was additionally carried out in 10 of those. Linkage analysis
      was performed using multi-point analysis in Superlink Online SNP 1.1. From
      prioritized linkage regions with a LOD score >= 2, a total of 24 genes harboring
      rare variants were selected. Those genes were taken forward and were jointly
      analyzed in gene-set analyses of exome-chip data using the MAGMA software in an
      independent sample of patients with persistent ADHD and healthy controls (N =
      9365). The gene-set including all 24 genes together, and particularly the gene
      set from one of the three families (12 genes), were significantly associated with
      persistent ADHD in this sample. Among the latter, gene-wide analysis for the
      AAED1 gene reached significance. A rare variant (rs151326868) within AAED1
      segregated with ADHD in one of the families. The analytic strategy followed here
      is an effective approach for identifying novel ADHD risk genes. Additionally,
      this study suggests that both rare and more frequent variants in multiple genes
      act together in contributing to ADHD risk, even in individual multi-case
      families.

PMID- 30116031
TI  - Cerebrospinal fluid markers of inflammation and infections in schizophrenia and
      affective disorders: a systematic review and meta-analysis.
AB  - Infections and inflammatory processes have been associated with the development
      of schizophrenia and affective disorders; however, no study has yet
      systematically reviewed all available studies on cerebrospinal fluid (CSF) immune
      alterations. We aimed to systematically review the CSF immunological findings in
      schizophrenia spectrum and affective disorders. We identified all studies
      investigating CSF inflammatory markers in persons with schizophrenia or affective
      disorders published prior to March 23, 2017 searching PubMed, CENTRAL, EMBASE,
      Psychinfo, and LILACS. Literature search, data extraction and bias assessment
      were performed by two independent reviewers. Meta-analyses with standardized mean
      difference (SMD) including 95% confidence intervals (CI) were performed on case
      healthy control studies. We identified 112 CSF studies published between 1942
      2016, and 32 case-healthy control studies could be included in meta-analyses.
      Studies varied regarding gender distribution, age, disease duration, treatment,
      investigated biomarkers, and whether recruitment happened consecutively or based
      on clinical indication. The CSF/serum albumin ratio was increased in
      schizophrenia (1 study [54 patients]; SMD = 0.62; 95% CI 0.24-1.00) and affective
      disorders (4 studies [302 patients]; SMD = 0.43; 95% CI 0.25-0.61, I2 = 0%),
      compared to healthy controls. Total CSF protein was elevated in both
      schizophrenia (3 studies [97 patients]; SMD = 0.38; 95% CI 0.12-0.65, I2 = 0%)
      and affective disorders (2 studies [53 patients]; SMD = 0.77; 95% CI 0.36-1.18,
      I2 = 0%). The IgG ratio was increased in schizophrenia (1 study [54 patients];
      SMD = 0.60; 95% CI 0.23-0.98), whereas the IgG Albumin ratio was decreased (1
      study [32 patients]; SMD = -0.62; 95%CI -1.13 to -0.12). Interleukin-6 (IL-6)
      levels (7 studies [230 patients]; SMD = 0.38; 95% CI 0.02-0.74; I2 = 64%) and IL
      8 levels (3 studies [95 patients]; SMD = 0.46; 95% CI 0.17-0.75, I2 = 0%) were
      increased in schizophrenia but not significantly increased in affective
      disorders. Most of the remaining inflammatory markers were not significantly
      different compared to healthy controls in the meta-analyses. However, in the
      studies which did not include healthy controls, CSF abnormalities were more
      common, and two studies found CSF dependent re-diagnosis in 3.2-6%. Current
      findings suggest that schizophrenia and affective disorders may have CSF
      abnormalities including signs of blood-brain barrier impairment and inflammation.
      However, the available evidence does not allow any firm conclusion since all
      studies showed at least some degree of bias and vastly lacked inclusion of
      confounding factors. Moreover, only few studies investigated the same parameters
      with healthy controls and high-quality longitudinal CSF studies are lacking,
      including impact of psychotropic medications, lifestyle factors and potential
      benefits of anti-inflammatory treatment in subgroups with CSF inflammation.

PMID- 30116032
TI  - Genetics of suicide attempts in individuals with and without mental disorders: a
      population-based genome-wide association study.
AB  - Family studies have shown an aggregation of suicidal behavior in families. Yet,
      molecular studies are needed to identify loci accounting for genetic
      heritability. We conducted a genome-wide association study and estimated single
      nucleotide polymorphisms (SNP) heritability for a suicide attempt. In a case
      cohort study, national data on all individuals born in Denmark after 1981 and
      diagnosed with severe mental disorders prior to 2013 (n = 57,377) and individuals
      from the general population (n = 30,000) were obtained. After quality control,
      the sample consisted of 6024 cases with an incidence of suicide attempt and
      44,240 controls with no record of a suicide attempt. Suggestive associations
      between SNPs, rs6880062 (p-value: 5.4 * 10-8) and rs6880461 (p-value: 9.5 * 10
      8), and suicide attempt were identified when adjusting for socio-demographics.
      Adjusting for mental disorders, three significant associations, all on chromosome
      20, were identified: rs4809706 (p-value: 2.8 * 10-8), rs4810824 (p-value: 3.5 *
      10-8), and rs6019297 (p-value: 4.7 * 108). Sub-group analysis of cases with
      affective disorders revealed SNPs associated with suicide attempts when compared
      to the general population for gene PDE4B. All SNPs explained 4.6% [CI-95: 2.9
      6.3%] of the variation in suicide attempt. Controlling for mental disorders
      reduced the heritability to 1.9% [CI-95: 0.3-3.5%]. Affective and autism spectrum
      disorders exhibited a SNP heritability of 5.6% [CI-95: 1.9-9.3%] and 9.6% [CI-95:
      1.1-18.1%], respectively. Using the largest sample to date, we identified
      significant SNP associations with suicide attempts and support for a genetic
      transmission of suicide attempt, which might not solely be explained by mental
      disorders.

PMID- 30116033
TI  - Rhizobacterial community structure in response to nitrogen addition varied
      between two Mollisols differing in soil organic carbon.
AB  - Excessive nitrogen (N) fertilizer input to agroecosystem fundamentally alters
      soil microbial properties and subsequent their ecofunctions such as carbon (C)
      sequestration and nutrient cycling in soil. However, between soils, the
      rhizobacterial community diversity and structure in response to N addition is not
      well understood, which is important to make proper N fertilization strategies to
      alleviate the negative impact of N addition on soil organic C and soil quality
      and maintain plant health in soils. Thus, a rhizo-box experiment was conducted
      with soybean grown in two soils, i.e. soil organic C (SOC)-poor and SOC-rich
      soil, supplied with three N rates in a range from 0 to 100 mg N kg-1. The
      rhizospheric soil was collected 50 days after sowing and MiSeq sequencing was
      deployed to analyze the rhizobacterial community structure. The results showed
      that increasing N addition significantly decreased the number of phylotype of
      rhizobacteria by 12.3%, and decreased Shannon index from 5.98 to 5.36
      irrespective of soils. Compared to the SOC-rich soil, the increases in abundances
      of Aquincola affiliated to Proteobacteria, and Streptomyces affiliated to
      Actinobacteria were greater in the SOC-poor soil in response to N addition. An
      opposite trend was observed for Ramlibacter belong to Proteobacteria. These
      results suggest that N addition reduced the rhizobacterial diversity and its
      influence on rhizobacterial community structure was soil-specific.

PMID- 30116035
TI  - Twenty-four-year trends and determinants of change in compliance with Swiss
      dietary guidelines.
AB  - BACKGROUND AND AIMS: A healthy diet is the cornerstone of disease prevention, and
      dietary guidelines have been issued in most countries. We aimed to assess trends
      in compliance with dietary guidelines in the population of Geneva, Switzerland.
      METHODS: Multiple cross-sectional, population-based surveys conducted between
      1993 and 2016 in the canton of Geneva, Switzerland [20,310 participants (52.3%
      women, mean age 51.9 +/- 10.7 years)]. Trends in compliance with the Swiss
      dietary guidelines regarding food intake were assessed using logistic regression
      (a) for each guideline and (b) for at least three guidelines. Compliance before
      and after the first and second issuing of the guidelines was assessed. RESULTS:
      After multivariable adjustment, compliance with fruits increased overall [odds
      ratio and (95% confidence interval) for 1-year increase: 1.007 (1.003-1.012), p <
      0.001], in men, participants aged over 45 and with low educational level.
      Compliance with vegetables increased overall [1.015 (1.008-1.022), p < 0.001], in
      both genders, age groups [45-54 and 55-64] and participants with low educational
      level. Compliance with meat increased in women [1.007 (1.001-1.013), p = 0.021]
      and participants with a university degree. Compliance with fresh fish increased
      in age group [55-64] [1.009 (1.000-1.018), p = 0.041]. Compliance with dairy
      products decreased overall [0.979 (0.972-0.986), p < 0.001] and in all groups
      studied, except for age group [65-74]. Compliance with at least three guidelines
      increased in age group [55-64] only [1.013 (1.002-1.024), p = 0.019]. No effect
      of the issuing of the guidelines was found. CONCLUSION: In the Geneva adult
      population, compliance with the Swiss dietary guidelines improved little. Issuing
      of dietary guidelines did not impact trends.

PMID- 30116034
TI  - Hazardous gases (CO, NOx, CH4 and C3H8) released from CO2 fertilizer unit lead to
      oxidative damage and degrades photosynthesis in strawberry plants.
AB  - CO2 boilers/direct heating systems used in greenhouses often lead to incomplete
      combustion, which results in the formation of hazardous gases, such as carbon
      monoxide (CO), nitroxide (NOX) and other hydrocarbons. In this study, strawberry
      plants that were grown on rockwool cubes were transferred to airtight bottles and
      treated with CO, NOX, CH4 and C3H8 gases for 1-48 hours. Oxidative damage due to
      hazardous gases was observed, as indicated by H2O2 and [Formula: see text]
      determination. Photosynthetic pigments were reduced, and stomatal guard cells
      were damaged and remained closed compared to the control. The activity of other
      photosynthetic parameters was negatively related to hazardous gases. Reduction in
      the expression of multiprotein complexes was highly observed under hazardous gas
      treatments. This study highlighted that hazardous gases (CO, NOX, CH4 and C3H8)
      emitted due to incomplete combustion of CO2 fertilization units/or direct heating
      systems resulted in the formation of ROS in shoots and limited photosynthetic
      metabolism. We predicted that major steps must be incorporated to improve the
      efficiency of CO2 boiler/heating systems to decrease the emission of these
      hazardous gases and other hydrocarbons and to reduce the observed risks that are
      key to the reduction of crops.

PMID- 30116037
TI  - Abundance and distribution of Archaea in the subseafloor sedimentary biosphere.
AB  - Subseafloor sedimentary environments harbor a remarkable number of microorganisms
      that constitute anaerobic and aerobic microbial ecosystems beneath the ocean
      margins and open-ocean gyres, respectively. Microbial biomass and diversity
      richness generally decrease with increasing sediment depth and burial time.
      However, there has been a long-standing debate over the contribution and
      distribution of Archaea in the subseafloor sedimentary biosphere. Here we show
      the global quantification of archaeal and bacterial 16S rRNA genes in 221
      sediment core samples obtained from diverse oceanographic settings through
      scientific ocean drilling using microfluidic digital PCR. We estimated that
      archaeal cells constitute 37.3% of the total microbial cells (40.0% and 12.8% in
      the ocean margin and open-ocean sites, respectively), corresponding to 1.1 * 1029
      cells on Earth. In addition, the relative abundance of archaeal 16S rRNA genes
      generally decreased with the depth of water in the overlying sedimentary habitat,
      suggesting that Archaea may be more sensitive to nutrient quality and quantity
      supplied from the overlying ocean.

PMID- 30116038
TI  - Biphasic cellular adaptations and ecological implications of Alteromonas
      macleodii degrading a mixture of algal polysaccharides.
AB  - Algal polysaccharides are an important bacterial nutrient source and central
      component of marine food webs. However, cellular and ecological aspects
      concerning the bacterial degradation of polysaccharide mixtures, as presumably
      abundant in natural habitats, are poorly understood. Here, we contextualize
      marine polysaccharide mixtures and their bacterial utilization in several ways
      using the model bacterium Alteromonas macleodii 83-1, which can degrade multiple
      algal polysaccharides and contributes to polysaccharide degradation in the
      oceans. Transcriptomic, proteomic and exometabolomic profiling revealed cellular
      adaptations of A. macleodii 83-1 when degrading a mix of laminarin, alginate and
      pectin. Strain 83-1 exhibited substrate prioritization driven by catabolite
      repression, with initial laminarin utilization followed by simultaneous
      alginate/pectin utilization. This biphasic phenotype coincided with pronounced
      shifts in gene expression, protein abundance and metabolite secretion, mainly
      involving CAZymes/polysaccharide utilization loci but also other functional
      traits. Distinct temporal changes in exometabolome composition, including the
      alginate/pectin-specific secretion of pyrroloquinoline quinone, suggest that
      substrate-dependent adaptations influence chemical interactions within the
      community. The ecological relevance of cellular adaptations was underlined by
      molecular evidence that common marine macroalgae, in particular Saccharina and
      Fucus, release mixtures of alginate and pectin-like rhamnogalacturonan. Moreover,
      CAZyme microdiversity and the genomic predisposition towards polysaccharide
      mixtures among Alteromonas spp. suggest polysaccharide-related traits as an
      ecophysiological factor, potentially relating to distinct 'carbohydrate
      utilization types' with different ecological strategies. Considering the
      substantial primary productivity of algae on global scales, these insights
      contribute to the understanding of bacteria-algae interactions and the
      remineralization of chemically diverse polysaccharide pools, a key step in marine
      carbon cycling.

PMID- 30116039
TI  - Picoeukaryotes of the Micromonas genus: sentinels of a warming ocean.
AB  - Photosynthetic picoeukaryotesx in the genus Micromonas show among the widest
      latitudinal distributions on Earth, experiencing large thermal gradients from
      poles to tropics. Micromonas comprises at least four different species often
      found in sympatry. While such ubiquity might suggest a wide thermal niche, the
      temperature response of the different strains is still unexplored, leaving many
      questions as for their ecological success over such diverse ecosystems. Using
      combined experiments and theory, we characterize the thermal response of eleven
      Micromonas strains belonging to four species. We demonstrate that the variety of
      specific responses to temperature in the Micromonas genus makes this
      environmental factor an ideal marker to describe its global distribution and
      diversity. We then propose a diversity model for the genus Micromonas, which
      proves to be representative of the whole phytoplankton diversity. This prominent
      primary producer is therefore a sentinel organism of phytoplankton diversity at
      the global scale. We use the diversity within Micromonas to anticipate the
      potential impact of global warming on oceanic phytoplankton. We develop a
      dynamic, adaptive model and run forecast simulations, exploring a range of
      adaptation time scales, to probe the likely responses to climate change. Results
      stress how biodiversity erosion depends on the ability of organisms to adapt
      rapidly to temperature increase.

PMID- 30116040
TI  - Genetic diversity and phenotypic plasticity of AHL-mediated Quorum sensing in
      environmental strains of Vibrio mediterranei.
AB  - N-Acyl homoserine lactone (AHL)-mediated Quorum sensing (QS) is one of the most
      studied social behavior among Proteobacteria. However, despite the current
      knowledge on QS-associated phenotypes such as bioluminescence, biofilm formation,
      or pathogenesis, the characterization of environmental factors driving QS in
      realistic ecological settings remains scarce. We investigated the dynamics of AHL
      and AHL-producing Vibrio among 840 isolates  collected fortnightly from the
      Salses-Leucate Mediterranean lagoon in spring and summer 2015 and 2016. Vibrio
      isolates were characterized by gyrB gene sequencing, Enterobacterial repetitive
      intergenic consensus polymerase chain reaction, and genome sequencing, and AHL
      production was investigated by a biosensors-based UHPLC-HRMS/MS approach. Our
      results revealed, for the first time, a succession of V. mediterranei isolates
      with different AHL production phenotypes over time and this dynamics was observed
      in a single genotype (average genomic nucleotide identity >99.9). A multivariate
      DistLM analysis revealed that 83.4% of the temporal variation of V. mediterranei
      QS phenotypes was explained by environmental variables. Overall, our results
      suggest that isolates of a single genotype are able to change their QS phenotypes
      in response to environmental conditions, highlighting the phenotypic plasticity
      of bacterial communication in the environment.

PMID- 30116041
TI  - Inter-Kingdom beach warfare: Microbial chemical communication activates natural
      chemical defences.
AB  - An inter-kingdom beach warfare between a Streptomyces sp. and Aspergillus sp. co
      isolated from shallow water beach sand, collected off Heron Island, Queensland,
      Australia, saw the bacteriostatic Aspergillus metabolite cyclo-(L-Phe-trans-4
      hydroxy-L-Pro) (3) stimulate the Streptomyces to produce nitric oxide (NO), which
      in turn mediated transcriptional activation of a silent biosynthetic gene cluster
      (BGC) for fungistatic heronapyrrole B (1). Structure activity relationship
      studies, coupled with the use of NO synthase inhibitors, donors and scavangers,
      and both genomic and transcriptomic analyses, confirmed the extraordinary
      chemical cue specificity of 3, and its NO-mediated mechanism of transcriptional
      action. Our findings reveal the importance of inter-kingdom (fungal-bacterial)
      chemical communication in the regulation of silent BGCs coding for chemical
      defenses. We propose that the detection and characterisation of NO mediated
      transcriptional activation (NOMETA) of silent chemical defences in the
      environment, may inspire broader application in the field of microbial
      biodiscovery.

PMID- 30116042
TI  - Periodic and coordinated gene expression between a diazotroph and its diatom
      host.
AB  - In the surface ocean, light fuels photosynthetic carbon fixation of
      phytoplankton, playing a critical role in ecosystem processes including carbon
      export to the deep sea. In oligotrophic oceans, diatom-diazotroph associations
      (DDAs) play a keystone role in ecosystem function because diazotrophs can provide
      otherwise scarce biologically available nitrogen to the diatom host, fueling
      growth and subsequent carbon sequestration. Despite their importance, relatively
      little is known about the nature of these associations in situ. Here we used
      metatranscriptomic sequencing of surface samples from the North Pacific
      Subtropical Gyre (NPSG) to reconstruct patterns of gene expression for the
      diazotrophic symbiont Richelia and we examined how these patterns were integrated
      with those of the diatom host over day-night transitions. Richelia exhibited
      significant diel signals for genes related to photosynthesis, N2 fixation, and
      resource acquisition, among other processes. N2 fixation genes were significantly
      co-expressed with host nitrogen uptake and metabolism, as well as potential genes
      involved in carbon transport, which may underpin the exchange of nitrogen and
      carbon within this association. Patterns of expression suggested cell division
      was integrated between the host and symbiont across the diel cycle. Collectively
      these data suggest that symbiont-host physiological ecology is strongly
      interconnected in the NPSG.

PMID- 30116043
TI  - Diverse diazotrophs are present on sinking particles in the North Pacific
      Subtropical Gyre.
AB  - Sinking particles transport carbon and nutrients from the surface ocean into the
      deep sea and are considered hot spots for bacterial diversity and activity. In
      the oligotrophic oceans, nitrogen (N2)-fixing organisms (diazotrophs) are an
      important source of new N but the extent to which these organisms are present and
      exported on sinking particles is not well known. Sinking particles were collected
      every 6 h over a 2-day period using net traps deployed at 150 m in the North
      Pacific Subtropical Gyre. The bacterial community and composition of diazotrophs
      associated with individual and bulk sinking particles was assessed using 16S rRNA
      and nifH gene amplicon sequencing. The bacterial community composition in bulk
      particles remained remarkably consistent throughout time and space while large
      variations of individually picked particles were observed. This difference
      suggests that unique biogeochemical conditions within individual particles may
      offer distinct ecological niches for specialized bacterial taxa. Compared to
      surrounding seawater, particle samples were enriched in different size classes of
      globally significant N2-fixing cyanobacteria including Trichodesmium, symbionts
      of diatoms, and the unicellular cyanobacteria Crocosphaera and UCYN-A. The
      particles also contained nifH gene sequences of diverse non-cyanobacterial
      diazotrophs suggesting that particles could be loci for N2 fixation by
      heterotrophic bacteria. The results demonstrate that diverse diazotrophs were
      present on particles and that new N may thereby be directly exported from surface
      waters on sinking particles.

PMID- 30116044
TI  - Functional metagenomics reveals abundant polysaccharide-degrading gene clusters
      and cellobiose utilization pathways within gut microbiota of a wood-feeding
      higher termite.
AB  - Plant cell-wall polysaccharides constitute the most abundant but recalcitrant
      organic carbon source in nature. Microbes residing in the digestive tract of
      herbivorous bilaterians are particularly efficient at depolymerizing
      polysaccharides into fermentable sugars and play a significant support role
      towards their host's lifestyle. Here, we combine large-scale functional screening
      of fosmid libraries, shotgun sequencing, and biochemical assays to interrogate
      the gut microbiota of the wood-feeding "higher" termite Globitermes
      brachycerastes. A number of putative polysaccharide utilization gene clusters
      were identified with multiple fibrolytic genes. Our large-scale functional
      screening of 50,000 fosmid clones resulted in 464 clones demonstrating plant
      polysaccharide-degrading activities, including 267 endoglucanase-, 24
      exoglucanase-, 72 beta-glucosidase-, and 101 endoxylanase-positive clones. We
      sequenced 173 functionally active clones and identified ~219 genes encoding
      putative carbohydrate-active enzymes (CAZymes) targeting cellulose, hemicellulose
      and pectin. Further analyses revealed that 68 of 154 contigs encode one or more
      CAZyme, which includes 35 examples of putative saccharolytic operons, suggesting
      that clustering of CAZymes is common in termite gut microbial inhabitants.
      Biochemical characterization of a representative xylanase cluster demonstrated
      that constituent enzymes exhibited complementary physicochemical properties and
      saccharolytic capabilities. Furthermore, diverse cellobiose-metabolizing enzymes
      include beta-glucosidases, cellobiose phosphorylases, and phopho-6-beta
      glucosidases were identified and functionally verified, indicating that the
      termite gut micro-ecosystem utilizes diverse metabolic pathways to interconnect
      hydrolysis and central metabolism. Collectively, these results provide an in
      depth view of the adaptation and digestive strategies employed by gut microbiota
      within this tiny-yet-efficient host-associated ecosystem.

PMID- 30116036
TI  - Author Correction: Genome-wide association and HLA fine-mapping studies identify
      risk loci and genetic pathways underlying allergic rhinitis.
AB  - In the version of this article initially published, in Fig. 3, the y-axis
      numbering did not match the log scale indicated in the axis label. The error has
      been corrected in the HTML and PDF version of the article.

PMID- 30116045
TI  - Reporter PET Images Bortezomib Treatment-Mediated Suppression of Cancer Cell
      Proteasome Activity.
AB  - Proteasomal protein degradation is a promising target for cancer therapy. Here,
      we developed a positron emission tomography (PET) technique based on the sodium
      iodide symporter (NIS) gene fused with the carboxyl-terminal of ornithine
      decarboxylase (cODC) that noninvasively images cancer cells with inhibited
      proteasome activity. A retroviral vector was constructed in which the murine cODC
      degron was fused to the human NIS gene (NIS-cODC). Transiently transduced CT26
      and HT29 colon cancer cells and stably expressing CT26/NIS-cODC cells were
      prepared. In cancer cells transiently transduced with NIS-cODC, NIS expression
      and transport activity was low at baseline, but NIS protein and 125I uptake was
      significantly increased by inhibition of proteasome activity with bortezomib.
      Stable CT26/NIS-cODC cells also showed increased cytosolic and membrane NIS by
      bortezomib, and four different stable clones displayed bortezomib dose-dependent
      stimulation of 125I and 99mTc-04- uptake. Importantly, bortezomib dose
      dependently suppressed survival of CT26/NIS-cODC clones in a manner that closely
      correlated to the magnitudes of 125I and 99mTc-04- uptake. CT26/NIS-cODC tumors
      of bortezomib-treated mice demonstrated greater 124I uptake on PET images and
      increased NIS expression on tissue staining compared to vehicle-injected animals.
      NIS-cODC PET imaging may allow noninvasive quantitative monitoring of proteasome
      activity in cancer cells treated with bortezomib.

PMID- 30116046
TI  - Targeting the NLRP3 inflammasome in inflammatory diseases.
AB  - This corrects the article DOI: 10.1038/nrd.2018.97.

PMID- 30116047
TI  - Spinal cord injury: Ion transporter agonist improves recovery.

PMID- 30116048
TI  - Pain: Silencing chronic pain with botulinum toxin.

PMID- 30116050
TI  - Regenerative medicine: Stem cell-derived cardiomyocytes heal a broken heart.

PMID- 30116052
TI  - Gene therapy: Gene therapy before the cradle.

PMID- 30116053
TI  - Corneal confocal microscopy detects corneal nerve damage and increased dendritic
      cells in Fabry disease.
AB  - Fabry disease is characterised by neuropathic pain and accelerated vascular
      disease. This study evaluates the utility of corneal confocal microscopy (CCM) to
      non-invasively quantify corneal nerve and endothelial cell morphology and
      dendritic cell (DC) density in relation to disease severity in subjects with
      Fabry disease. Seventeen consecutive participants with Fabry disease and 17
      healthy control subjects were included in this cross-sectional study. Fabry
      disease severity was measured using the Mainz Severity Score Index (MSSI).
      Central corneal sensitivity was assessed with a contact corneal esthesiometer.
      There was a significant reduction in the corneal sensitivity (5.75 [5.25-6.00]
      vs. 6.00 [6.00-6.00] cm, P = 0.014), nerve fiber density (NFD) (26.4 +/- 10.1 vs.
      33.7 +/- 7.9 fibers/mm2, P = 0.025) and nerve fiber length (NFL) (15.9 +/- 3.4
      vs. 19.5 +/- 4.4 mm/mm2, P = 0.012) and an increase in DC density (38.3 [17.5
      97.3] vs. 13.5 [0-29.4] cells/mm2, P = 0.004) in subjects with Fabry disease
      compared to the healthy control subjects. The total MSSI score correlated with
      NFD (rho = -0.686; P = 0.006), NFL (rho = -0.692; P = 0.006), endothelial cell
      density (rho = -0.511; P = 0.036), endothelial cell area (rho = 0.514; P = 0.036)
      and alpha-galactosidase A enzyme activity (rho = -0.723; P = 0.008). This study
      demonstrates reduced corneal sensitivity, corneal nerve fiber damage and
      increased DCs in subjects with Fabry disease.

PMID- 30116049
TI  - New approaches and challenges to targeting the endocannabinoid system.
AB  - The endocannabinoid signalling system was discovered because receptors in this
      system are the targets of compounds present in psychotropic preparations of
      Cannabis sativa. The search for new therapeutics that target endocannabinoid
      signalling is both challenging and potentially rewarding, as endocannabinoids are
      implicated in numerous physiological and pathological processes. Hundreds of
      mediators chemically related to the endocannabinoids, often with similar
      metabolic pathways but different targets, have complicated the development of
      inhibitors of endocannabinoid metabolic enzymes but have also stimulated the
      rational design of multi-target drugs. Meanwhile, drugs based on botanical
      cannabinoids have come to the clinical forefront, synthetic agonists designed to
      bind cannabinoid receptor 1 with very high affinity have become a societal threat
      and the gut microbiome has been found to signal in part through the
      endocannabinoid network. The current development of drugs that alter
      endocannabinoid signalling and how this complex system could be pharmacologically
      manipulated in the future are described in this Opinion article.

PMID- 30116055
TI  - Advancing internal exposure and physiologically-based toxicokinetic modeling for
      21st-century risk assessments.
AB  - Scientifically sound, risk-informed evaluation of chemicals is essential to
      protecting public health. Systematically leveraging information from exposure,
      toxicology, and epidemiology studies can provide a holistic understanding of how
      real-world exposure to chemicals may impact the health of populations, including
      sensitive and vulnerable individuals and life-stages. Increasingly, public health
      policy makers are employing toxicokinetic (TK) modeling tools to integrate these
      data streams and predict potential human health impact. Development of a suite of
      tools for predicting internal exposure, including physiologically-based
      toxicokinetic (PBTK) models, is being driven by needs to address large numbers of
      data-poor chemicals efficiently, translate bioactivity, and mechanistic
      information from new in vitro test systems, and integrate multiple lines of
      evidence to enable scientifically sound, risk-informed decisions. New modeling
      approaches are being designed "fit for purpose" to inform specific decision
      contexts, with applications ranging from rapid screening of hundreds of
      chemicals, to improved prediction of risks during sensitive stages of
      development. New data are being generated experimentally and computationally to
      support these models. Progress to meet the demand for internal exposure and PBTK
      modeling tools will require transparent publication of models and data to build
      credibility in results, as well as opportunities to partner with decision makers
      to evaluate and build confidence in use of these for improved decisions that
      promote safe use of chemicals.

PMID- 30116057
TI  - EMA and FDA prune the checkpoint inhibitor treatment landscape.

PMID- 30116054
TI  - Epidemic history of hepatitis C virus genotypes and subtypes in Portugal.
AB  - Any successful strategy to prevent and control HCV infection requires an
      understanding of the epidemic behaviour among the different genotypes. Here, we
      performed the first characterization of the epidemic history and transmission
      dynamics of HCV subtypes in Portugal. Direct sequencing of NS5B was performed on
      230 direct-acting antiviral drugs (DAA)-treatment naive patients in Lisbon.
      Phylogenetic analysis was used for subtyping and transmission cluster
      identification. Bayesian methods were used to reconstruct the epidemic history of
      HCV subtypes. Sequences were analysed for resistance-associated substitutions
      (RAS). The majority of strains were HCV-GT1 (62.6%), GT3 (18.3%, all subtype 3a)
      and GT4 (16.1%). Among GT1, the most frequent were subtypes 1a (75.5%) and 1b
      (24.5%). Polyphyletic patterns were found in all but 12 lineages suggesting
      multiple introductions of the different subtypes in this population. Five
      distinct epidemics were identified. The first significant HCV epidemic in
      Portugal occurred between 1930s and 1960s, was caused almost exclusively by GT1b
      and was likely associated with blood transfusions. Rapid expansion of GT3a
      occurred in the 1960s and GT1a in the 1980s, associated with intravenous drug
      use. The most recent epidemics were caused by GT4a and GT4d and seem to be
      associated with the resurgence of opioid use. The C316N substitution was found in
      31.4% of GT1b-patients. Close surveillance of patients bearing this mutation and
      undergoing dasabuvir-based regimens will be important to determine its impact on
      treatment outcome.

PMID- 30116058
TI  - A genome project for Maori and Pasifika: charting a path to equity in genomic
      medicine for Aotearoa.

PMID- 30116059
TI  - Is there a place for day hospitals in older persons mental health care?

PMID- 30116056
TI  - Investigating the role of landscape composition on honey bee colony winter
      mortality: A long-term analysis.
AB  - The health of honey bee colonies is, amongst others, affected by the amount,
      quality and diversity of available melliferous plants. Since landscape is highly
      diverse throughout Austria regarding the availability of nutritional resources,
      we used data from annual surveys on honey bee colony losses ranging over six
      years to analyse a possible relationship with land use. The data set comprises
      reports from a total of 6,655 beekeepers and 129,428 wintered honey bee colonies.
      Regions surrounding the beekeeping operations were assigned to one of six
      clusters according to their composition of land use categories by use of a
      hierarchical cluster analysis, allowing a rough distinction between urban
      regions, regions predominated by semi-natural areas and pastures, and mainly
      agricultural environments. We ran a Generalised Linear Mixed Model and found
      winter colony mortality significantly affected by operation size, year, and
      cluster membership, but also by the interaction of year and cluster membership.
      Honey bee colonies in regions composed predominantly of semi-natural areas,
      coniferous forests and pastures had the lowest loss probability in four out of
      six years, and loss probabilities within these regions were significantly lower
      in five out of six years compared to those within regions composed predominantly
      of artificial surfaces, broad-leaved and coniferous forest.

PMID- 30116060
TI  - Provincial or Tertiary Surgical Treatment for Rectal Cancer in New Zealand?

PMID- 30116061
TI  - Psychogeriatric day hospital reduces depression and anxiety symptoms and improves
      quality of life.
AB  - AIMS: To measure changes in depression and anxiety symptoms, as well as quality
      and satisfaction with life in older adults attending a psychogeriatric day
      hospital. METHODS: One hundred and eighty-five consecutive patients (24% male)
      provided self-report data at intake and discharge. RESULTS: Patients showed
      significant reductions in anxiety and depressive symptoms and significantly
      improved quality of life and satisfaction with life. All changes were of moderate
      effect size. CONCLUSION: Attending a psychogeriatric day hospital that provides
      time-limited personalised care is associated with statistically significant and
      clinically meaningful reductions in anxious and depressive symptoms for patients,
      as well as increasing subjective satisfaction and quality of life. Given the
      projected rise in the number of older adults in coming decades, the establishment
      of more psychogeriatric day hospitals should be considered as an alternative to
      expensive and stretched inpatient services.

PMID- 30116062
TI  - A multicentre, benchmarking study of rectal cancer management in provincial New
      Zealand hospitals.
AB  - AIM: The quality of rectal cancer management within New Zealand provincial
      hospitals is largely unknown. This study was conducted to appraise and benchmark
      the management of rectal cancer in provincial New Zealand centres as compared to
      specialist tertiary centres. METHOD: Retrospective data was collected for all
      patients who underwent elective rectal cancer resection in six provincial New
      Zealand hospitals from January 2012 to December 2013. This was then compared with
      data from two tertiary hospitals over the same time period. The complete
      management pathway was evaluated. RESULTS: A total of 124 provincial and 145
      tertiary rectal cancer resections were analysed. Completeness of preoperative
      staging was comparable between provincial and tertiary centres, as was type of
      surgical procedure performed and rates of clear surgical margins. A statistically
      significant difference was observed in mean number of lymph nodes analysed (10.3
      v 17.2), reporting of mesorectal grade (61% v 77%), and completion colonoscopy
      rates (91% v 99%), all of which were lower in provincial hospitals.
      Multidisciplinary team discussion, rates of neoadjuvant therapy and post
      operative parameters such as 30-day mortality (0.8% v 1.4%), length of stay (11.9
      v 12.4 days), anastomotic leak (7% v 5%) and return to theatre (8% v 8%), were
      similar. CONCLUSION: Management of rectal cancer in provincial hospitals is
      comparable to specialist centres, however lymph node harvest, reporting of
      mesorectal grade and complete colonoscopy were factors identified which were
      lower in the provincial group. Provincial rectal cancer management remains an
      important resource for patients living outside major centres.

PMID- 30116063
TI  - What keeps Northland general practitioners working in Northland?
AB  - AIMS: The aim of this study was to understand why general practitioners continue
      living and practicing in Northland. METHODS: The study was qualitative in nature.
      Ten Northland GPs were interviewed. Interviews were analysed using an evolved
      grounded theory approach based on the sociological perspective of symbolic
      interactionism. RESULTS: Results from the study indicated that doctors whose
      values, and those of their developing families, are compatible with the
      accessible and affordable experiences that the physical environment of Northland
      provides, will stay in Northland. This connection intertwines with the value of
      family commitments and opportunities in the region. Both will not be shaken by
      professional or practice factors that, if positive, will only reinforce the depth
      of commitment to the region. CONCLUSIONS: When selecting students or GP
      registrars to provincial areas or recruiting new GPs to those areas, the values,
      family connections and lifestyle desires of the candidate and their family should
      match the environment offered by the region in order to improve retention in that
      region.

PMID- 30116064
TI  - A media content analysis of New Zealand's district health board Population-Based
      Funding Formula.
AB  - AIM: The Population-Based Funding Formula (PBFF) has a significant impact on
      health funding distribution between New Zealand's 20 district health boards
      (DHBs) yet is subject to little independent oversight or public scrutiny. There
      has been widespread dissatisfaction among DHBs with the allocation process;
      however, there are limited formal avenues available for DHBs and the public to
      discuss the PBFF. As such, the news media has become a key platform for voicing
      concerns. This study aims to gain a better understanding of how the PBFF is
      portrayed in the news media and of perceptions of funding allocations across the
      country. METHOD: We conducted thematic analyses of 487 newspaper articles about
      the PBFF, published over 13 years from 2003-2016. We then identified trends in
      the data. RESULTS: Typically presented in a negative light, the PBFF was commonly
      framed against a background of financial struggle and resultant impacts on health
      services and staff. The effect of factors driving DHB allocations and the PBFF
      process itself were also key themes. There were significant regional and temporal
      variations in reporting volume, with most articles focusing on South Island DHBs
      and occurring during the introduction of the PBFF and at the time of the most
      recent review. CONCLUSIONS: The findings suggest general discontent with the PBFF
      model across the DHB sector and a sense that the PBFF has failed to address
      various challenges facing DHBs. The geographic imbalance in reporting volume
      suggests that frustration with the PBFF is particularly keenly felt in the South
      Island. Although the PBFF is a lightning rod for frustrations over limited health
      funding, the findings point to the need to improve transparency and dialogue
      around the formula and to monitor of the impact of PBFF allocations throughout
      the country.

PMID- 30116065
TI  - Ethnic disparities in community antibacterial dispensing in New Zealand, 2015.
AB  - AIMS: There are significant ethnic disparities in the incidence of various
      infectious diseases in New Zealand. Antimicrobial stewardship interventions which
      ignore these disparities may have negative effects on the health of some ethnic
      groups. We aimed to determine the relationship between ethnicity and community
      antimicrobial dispensing in New Zealand, to inform the development of
      antimicrobial stewardship interventions in New Zealand. METHODS: Demographic data
      on all patients registered with a general practice in New Zealand and on all
      community pharmacy antibacterial dispensings during 2015 were obtained from
      national healthcare databases. The rates of dispensing were measured as the
      number of dispensings per 1,000 population per day and as defined daily doses per
      1,000 population per day. RESULTS: The rate of community antibacterial dispensing
      for the total population surveyed was 3.01 dispensings per 1,000 population per
      day, and was 3.49 for Pacific, 3.23 for Maori, 3.02 for European, 2.70 for Middle
      Eastern, Latin American and African, and 2.35 for Asian people. In all ethnic
      groups the rate of community antibacterial dispensing increased with increasing
      socioeconomic deprivation. Seasonal variation in antibacterial dispensing ranged
      between 34% in Asian people and 24% in European people. CONCLUSIONS: The ethnic
      disparities in the rates of antibacterial dispensing in New Zealand are
      consistent with, but less marked than, the ethnic disparities in the incidence of
      infectious diseases in New Zealand. Improved community-wide understanding of both
      the benefits and the harms of antibacterial medicines is necessary to support
      improved antibacterial use in New Zealand in the future.

PMID- 30116051
TI  - Promoting the clearance of neurotoxic proteins in neurodegenerative disorders of
      ageing.
AB  - Neurodegenerative disorders of ageing (NDAs) such as Alzheimer disease, Parkinson
      disease, frontotemporal dementia, Huntington disease and amyotrophic lateral
      sclerosis represent a major socio-economic challenge in view of their high
      prevalence yet poor treatment. They are often called 'proteinopathies' owing to
      the presence of misfolded and aggregated proteins that lose their physiological
      roles and acquire neurotoxic properties. One reason underlying the accumulation
      and spread of oligomeric forms of neurotoxic proteins is insufficient clearance
      by the autophagic-lysosomal network. Several other clearance pathways are also
      compromised in NDAs: chaperone-mediated autophagy, the ubiquitin-proteasome
      system, extracellular clearance by proteases and extrusion into the circulation
      via the blood-brain barrier and glymphatic system. This article focuses on
      emerging mechanisms for promoting the clearance of neurotoxic proteins, a
      strategy that may curtail the onset and slow the progression of NDAs.

PMID- 30116066
TI  - Antipsychotic prescribing in New Zealand between 2008 and 2015.
AB  - AIM: To examine antipsychotic prescribing trends in New Zealand adults from 2008
      2015. METHODS: Antipsychotic prescribing data was sourced via the Ministry of
      Health. Data were examined by year, type of drug, ethnicity, gender, age and
      location of district health board. RESULTS: All individuals dispensed an
      antipsychotic were included. Rates of antipsychotic prescribing rose from 1.88%
      to 2.81%, an increase of 49% over the seven years. Most of the increase was in
      atypical antipsychotics (particularly quetiapine and olanzapine), which accounted
      for 82% of total antipsychotics in 2015. Maori were prescribed more
      antipsychotics than non-Maori. Asian people had the lowest rate of prescribing
      (0.86%). The highest rate of antipsychotic use was in European females aged 65
      plus. CONCLUSION: Rates of antipsychotic prescription are increasing. Most of
      this change is in prescribing atypical antipsychotics. Young Maori males and
      elderly European females are most likely to receive antipsychotics.

PMID- 30116067
TI  - First, do no harmony: an examination of attitudes to music played in operating
      theatres.
AB  - AIM: It is common for music to be played in operating theatres around the world.
      The benefits or harms of this music on practitioners and patients are not well
      known. The aim of this paper is to examine the attitudes and perceptions of
      theatre staff towards the presence of music during operations on the theatre
      environment. METHOD: This observational study was conducted in a single-centre at
      a tertiary teaching hospital in New Zealand. Over a two-week period in 2014, the
      entire theatre staff population were sent an online survey. We gathered data on
      demographics (eg, age, gender, theatre role), perceived frequency of music being
      played in operating rooms, types of music, disposition to music in different
      situations, the perception of an effect on the theatre team, and on with whom the
      decision to have music played lay with. Appropriate statistical analyses were
      applied. RESULTS: A hundred and six responses were received (45% response rate).
      98% of people said that music is played in their operating rooms, with 50% saying
      it was played more than 50% of the time. 60% liked having it, whereas 30%
      disliked it. Easy Listening was the genre most played closely followed by Pop and
      Classical. Easy Listening was the most preferred and classical music the second
      most. Music was preferred for longer, more familiar and non-urgent procedures, at
      a low to medium volume, preferably from a CD or MP3 player, though 84% felt it
      was a distraction in a crisis situation. Surgeons were the most empowered group,
      and anaesthetic technicians the least when it came to choosing music. Most
      respondents felt music improved calmness, overall mood, overall team performance
      and surgeon's performance, though worsened communication. CONCLUSION: This study,
      while limited in size, demonstrates that theatre staff generally like music in
      the operating theatre, and most believe it has a positive impact on several
      aspects of the theatre environment, though a negative influence on communication.
      There have been no clinical impact studies on patient and this could be an avenue
      for future research.

PMID- 30116068
TI  - An audit of regular medication compliance prior to presentation for elective
      surgery.
AB  - AIM: Patients presenting for elective surgery frequently omit one or more regular
      medications. There is evidence that withholding some medication classes may lead
      to harm in the peri-operative period. We aim to quantify medication non
      compliance in an adult, elective surgical population and identify the reasons for
      this non-compliance. METHOD: Data was collected over a four-week period at an
      elective surgical facility on adult patients presenting for surgery. Surgery and
      anaesthesia type, the names of regular medications and reasons for omission were
      recorded. This information was matched to pharmacy data for six months prior to
      the audit. RESULTS: Six hundred and ninety-two patients underwent surgery during
      the audit period. Data for 631 patients (91%) was collected. Three hundred and
      sixty-six (58%) were prescribed regular medications. After exclusion of diabetic
      medication, 109 patients (30%) had missed one or more regular medications. Thirty
      four patients (31%) were non-compliant with medication due to fasting. Twenty
      seven patients (25%) were confused. Ten percent and 21% of patients prescribed
      beta-blockers or calcium channel blockers respectively were non-compliant on the
      day of surgery. CONCLUSIONS: A significant number of patients were non-compliant
      with their regular medication on the day of surgery. This represents a
      preventable source of risk that could be addressed by improved patient education
      or improved organisational pathways.

PMID- 30116069
TI  - Genomic medicine must reduce, not compound, health inequities: the case for
      hauora-enhancing genomic resources for New Zealand.
AB  - Precision medicine seeks to draw on data from both individuals and populations
      across disparate domains to influence and support diagnosis, management and
      prevention in healthcare at the level of the individual patient and their
      family/whanau. Central to this initiative is incorporating the effects of the
      inherent variation that lies within genomes and can influence health outcomes.
      Identifying and interpreting such variation requires an accurate, valid and
      representative dataset to firstly define what variants are present and then
      assess the potential relevance for the health of a person, their family/whanau
      and the wider community to which they belong. Globally the variation embedded
      within genomes differs enormously and has been shaped by the size, constitution,
      historical origins and evolutionary history of their source populations. Maori,
      and more broadly Pacific peoples, differ substantially in terms of genomic
      variation compared to the more closely studied European and Asian populations. In
      the absence of accurate genomic information from Maori and Pacific populations,
      the precise interpretation of genomic data and the success and benefits of
      genomic medicine will be disproportionately less for those Maori and Pacific
      peoples. In this viewpoint article we, as a group of healthcare professionals,
      researchers and scientists, present a case for assembling genomic resources that
      catalogue the characteristics of the genomes of New Zealanders, with an emphasis
      on peoples of Maori and Polynesian ancestry, as a healthcare imperative. In
      proposing the creation of these resources, we note that their governance and
      management must be led by iwi and Maori and Pacific representatives. Assembling a
      genomic resource must be informed by cultural concepts and values most especially
      understanding that, at a physical and spiritual level, whakapapa is embodied
      within the DNA of a person. Therefore DNA and genomic data that connects to
      whakapapa (genealogy) is considered a taonga (something precious and
      significant), and its storage, utilisation and interpretation is a culturally
      significant activity. Furthermore, such resources are not proposed to primarily
      enable comparisons between those with Maori and broader Pacific ancestries and
      other Aotearoa peoples but to place an understanding of the genetic contributors
      to their health outcomes in a valid context. Ongoing oversight and governance of
      such taonga by Maori and Pacific representatives will maximise hauora (health)
      while also minimising the risk of misuse of this information.

PMID- 30116071
TI  - A new report on the effects of a policy used to restrict access to elective
      inguinal hernia surgery.

PMID- 30116070
TI  - Redundant laparoscopic adjustable gastric band tubing causing internal hernia and
      small bowel obstruction.

PMID- 30116072
TI  - LIMIT CYCLES CAN REDUCE THE WIDTH OF THE HABITABLE ZONE.
AB  - The liquid water habitable zone (HZ) describes the orbital distance at which a
      terrestrial planet can maintain above-freezing conditions through regulation by
      the carbonate-silicate cycle. Recent calculations have suggested that planets in
      the outer regions of the HZ cannot maintain stable, warm climates, but rather
      should oscillate between long, globally glaciated states and shorter periods of
      climatic warmth. Such conditions, similar to "Snowball Earth" episodes
      experienced on Earth, would be inimical to the development of complex land life,
      including intelligent life. Here, we build on previous studies with an updated
      energy balance climate model to calculate this "limit cycle" region of the HZ
      where such cycling would occur. We argue that an abiotic Earth would have a
      greater CO2 partial pressure than today because plants and other biota help to
      enhance the storage of CO2 in soil. When we tune our abiotic model accordingly,
      we find that limit cycles can occur but that previous calculations have
      overestimated their importance. For G stars like the Sun, limit cycles occur only
      for planets with CO2 outgassing rates less than that on modern Earth. For K- and
      M-star planets, limit cycles should not occur; however, M-star planets may be
      inhospitable to life for other reasons. Planets orbiting late G-type and early K
      type stars retain the greatest potential for maintaining warm, stable conditions.
      Our results suggest that host star type, planetary volcanic activity, and
      seafloor weathering are all important factors in determining whether planets will
      be prone to limit cycling.

PMID- 30116073
TI  - Do bonuses affect teacher staffing and student achievement in high poverty
      schools? Evidence from an incentive for national board certified teachers in
      Washington State.
AB  - We study a teacher incentive policy in Washington State that awards a financial
      bonus to National Board certified teachers in high poverty schools. Using a
      regression discontinuity design, we find that the bonus policy increased the
      proportion of certified teachers in bonus-eligible schools by improving hiring,
      increasing certification rates of incumbent teachers, and reducing turnover.
      Depending on the method, we estimate that the proportion of NBCTs in treated
      schools increased by about four to eight percentage points over the first five
      years of eligibility. However, the improvement in certification rates corresponds
      to a change of about 0.2-0.3% of a standard deviation in teacher quality per year
      and we do not find evidence that the bonus resulted in detectible effects on
      student test achievement.

PMID- 30116074
TI  - Fast-tracking of new drugs: getting the balance right.

PMID- 30116076
TI  - Travelling with medicines in 2018.

PMID- 30116075
TI  - Electronic medication management.

PMID- 30116077
TI  - Infantile colic.

PMID- 30116079
TI  - Dentistry concerns for patients taking anticoagulants and antiplatelet drugs.

PMID- 30116078
TI  - Combining anticoagulation and antiplatelet drugs in coronary artery disease.

PMID- 30116080
TI  - Brief interventions for alcohol and other drug use.

PMID- 30116081
TI  - Communication and ciprofloxacin-associated acute kidney injury.

PMID- 30116082
TI  - Atezolizumab for non-small cell lung cancer.

PMID- 30116083
TI  - Ocrelizumab for multiple sclerosis.

PMID- 30116084
TI  - Palbociclib for breast cancer.

PMID- 30116085
TI  - Silodosin for benign prostatic hypertrophy.

PMID- 30116086
TI  - Guanfacine hydrochloride for attention deficit hyperactivity disorder.

PMID- 30116087
TI  - 'LaDePa' process for the drying and pasteurization of faecal sludge from VIP
      latrines using infrared radiation.
AB  - This paper studies a faecal sludge treatment process, LaDePa (Latrine Dehydration
      and Pasteurization), which includes: (i) the characterization of the rheological
      and plastic behaviour of faecal sludge in the feeding section; (ii) the study of
      the drying and pasteurization performance of the process using a laboratory-scale
      prototype; and (iii) an evaluation of the processed faecal sludge for reuse in
      agriculture or as a biofuel. Experiments conducted using a rheometer show that
      the faecal sludge exhibits shear thinning behaviour, i.e. viscosity decrease with
      shear rate increase. Plasticity tests in a cone penetrometer showed that the
      faecal sludge has a more liquid than plastic behaviour, which may affect
      extrusion quality, unless a plasticizer is added, as sawdust in this study. The
      extent of drying and pasteurization of the samples was determined based on
      moisture content and the presence of viable Ascaris eggs respectively. As the
      intensity of infrared radiation was increased, drying was faster and more
      efficient in terms of energy consumption. However, the pellets were thermally
      degraded at temperatures above 200  degrees C. After processing in the LaDePa,
      Ascaris eggs were deactivated or severely damaged so that they would be not able
      to develop. The last part of the study was conducted by determining the content
      of nutrients (C, N, P, K) and calorific value. The results showed that the
      processed pellets have suitable characteristics for reuse in agriculture and as a
      biofuel: similar nutrient content to manure and compost, and similar calorific
      value to wood. Drying did not affect the nutrient content and calorific value of
      the dry bone of faecal sludge.

PMID- 30116088
TI  - Editorial: Critical Race Theory: Why Should We Care about Applying It in our
      Research?

PMID- 30116089
TI  - Editorial: Critical Race Theory - We Are all Others.
AB  - Over the past two years, the persistence of racism in the United States has been
      particularly pronounced in the policies and actions of the administration of
      President Donald J. Trump; however, the structure of the United States has been
      racialized since its inception. This supplement of Ethnicity & Disease uses
      Critical Race Theory (CRT) to explore several implications for public health and
      public health research. We intend for it to spark conversations in the classroom
      and among researchers on how racial phenomena operate and how we as a field can
      address racism.

PMID- 30116090
TI  - Commentary: Just What is Critical Race Theory and What's it Doing in a
      Progressive Field like Public Health?
AB  - Gloria Ladson-Billings cautiously promotes the use of Critical Race Theory (CRT)
      to address racism's contribution to educational disparities. Nearly a decade ago,
      we issued a similar call to the multidisciplinary field of public health. Public
      health touts its progressive roots and focus on equity, but do those efforts draw
      on CRT? To answer this question, we define CRT, describe its origin in the field
      of law, and review the ways its use has grown in the field of public health.
      Public health interventions and policies rely heavily on evidence; therefore, we
      re-introduce the semi-structured research method we developed to facilitate
      empirical application of CRT, ie, the Public Health Critical Race Praxis (PHCRP).

PMID- 30116091
TI  - Toward the Science and Practice of Anti-Racism: Launching a National Campaign
      Against Racism.

PMID- 30116092
TI  - Ensnared by Colorblindness: Discourse on Health Care Disparities.
AB  - Objective: Race consciousness serves as the foundation for Critical Race Theory
      (CRT) methodology. Colorblindness minimizes racism as a determinant of outcomes.
      To achieve the emancipatory intent of CRT and to reduce health care disparities,
      we must understand: 1) how colorblindness "shows up" when health care
      professionals aim to promote equity; 2) how their colorblindness informs (and is
      informed by) clinical practice; and 3) ways to overcome colorblindness through
      strategies grounded in CRT. Design/Setting/Participants: We conducted 21 semi
      structured interviews with key informants and seven focus groups with personnel
      employed by a large Minnesota health care system. We coded transcripts
      inductively and deductively for themes using the constant comparative method. We
      used a race-conscious approach to examine how respondents' accounts align or
      diverge from colorblindness. Results: Evading race, respondents considered
      socioeconomic status, cultural differences, and patients' choices to be the main
      contributors to health disparities. Few criticized the behavior of coworkers or
      that of the organization or acknowledged structural racism. Respondents strongly
      believed that all patients were treated equally by providers and staff, in part
      due to race-neutral care processes and guidelines. Respondents also used several
      semantic moves common to colorblindness to refute suggestions of racial
      inequality. Conclusions: Colorblindness upholds the racial status quo and
      inhibits efforts to promote health equity. Drawing on CRT to guide them, health
      care leaders will need to develop strategies to counter personnel's tendency to
      focus on axes of inequality other than race, to decontextualize patients' health
      behaviors and choices, and to depend heavily on race-neutral care processes to
      produce equitable outcomes.

PMID- 30116093
TI  - "I think that's all a lie...I think It's genocide": Applying a Critical Race
      Praxis to Youth Perceptions of Flint Water Contamination.
AB  - Background: In April 2014, the emergency manager of Flint, Michigan switched the
      city's water supplier from Detroit's water department to the Flint River. The
      change in water source resulted in the Flint Water Crisis (FWC) in which lead
      (Pb) from the city's network of old pipes leached into residents' tap water.
      Residents of Flint reported concerns about the water to officials; however, the
      concerns were ignored for more than a year. Objective: This study sought to
      understand how Black youth in Flint conceptualize, interpret, and respond to
      racism they perceive as part of the normal bureaucracy contributing to the FWC.
      Methods: In 2016, we conducted four community forums with Flint youth aged 13 to
      17 years. Sixty-eight youth participated with 93% self-identifying as Black.
      Participants completed a brief survey. We audio-recorded the forums and
      transcribed them verbatim. Critical Race Theory (CRT) guided the development of
      the interview protocol and Public Health Critical Race Praxis (PHCRP) served as
      an interpretive framework during qualitative data analysis. Content analyses were
      completed using software. Results: Many youth viewed the FWC through a racially
      conscious frame. They described Flint as a Black city where historical and
      contemporary forms of racial stratification persist. Some described the
      contamination of the city's water as a form of genocide targeting Blacks.
      Conclusions: The findings from this exploratory study suggest some Black youth in
      Flint have difficulty coping with the FWC. Those who perceive it through a racial
      frame attribute the crisis to racism. They feel distressed about this and other
      traumas (eg, failure to address high rates of crime) they perceived as racism
      related. Future research should examine the implications for specific mental
      health outcomes among youth.

PMID- 30116094
TI  - Commentary: The Invention of Aboriginal Diabetes: The Role of the Thrifty Gene
      Hypothesis in Canadian Health Care Provision.
AB  - The purpose of this study was to analyze the extent to which the 'thrifty gene
      hypothesis' remains embedded within regimes of Canadian health care. The thrifty
      gene hypothesis, formulated by the American geneticist and travelling scientist
      James V. Neel in 1962, proposed that Indigenous peoples were genetically
      predisposed to Type 2 diabetes due to the foodways of their ancestors. The
      hypothesis was functionally racist and based on what biological anthropologists
      now call 'the myth of forager food insecurity.' Importantly, Neel reconsidered
      his own hypothesis in 1982 before he ultimately rejected it in 1999; nonetheless,
      in the mid-1990s, a team of Canadian scientists led by the endocrinologist Robert
      Hegele of Western University conducted a genetic study on the OjiCree community
      of Sandy Lake First Nation in northern Ontario. Thereafter, Hegele told the
      academic world and news media that he had discovered a thrifty gene in Sandy
      Lake. Like Neel, Hegele later came to reject his own study in 2011. Nonetheless,
      the 'thrifty gene hypothesis' and Hegele's Sandy Lake study continue to be cited,
      referenced, and reproduced in the current Clinical Guidelines of the Canadian
      Diabetes Association, as well as across state-related health literature more
      broadly. The purpose of this study, then, will be to apply the PHCRP to the
      thrifty gene hypothesis in a Canadian context.

PMID- 30116095
TI  - The Intersectionality of Racial and Gender Discrimination among Teens Exposed to
      Dating Violence.
AB  - Objective: Driven by intersectionality, a central tenet of Critical Race Theory,
      this study examines the combined associations of racial and gender
      discrimination, which are interlocking, macro-level social forces, and teen
      dating violence (TDV). Design: Self-report surveys were administered via Audio
      Computer Assisted Self Interview (ACASI) equipment. Logistic regression models
      were used to estimate associations between racial and gender discrimination and
      TDV. Setting: Study participants were recruited during August 2003 to June 2004
      from high school health classes and an after-school program located in South
      Bronx neighborhoods of New York City. Participants: Non-probability sample of 142
      Black and Latino teens aged 13-19 years who reported experiences dating someone
      of a different sex. Main Measures: Experienced discrimination based on race and
      gender adapted from the Experiences of Discrimination (EOD) instrument, dating
      violence items from the Youth Dating Violence Survey. Results: Of the
      participants, 40.1% reported experiencing both racial and gender discrimination,
      and nearly all (93%) experienced dating violence. Participants reporting both
      racial and gender discrimination were 2.5 times more likely to report
      experiencing the highest frequency of dating violence, adjusted for age and sex
      (95% CI: 1.0-6.7). A dose-response of EOD observed in unadjusted models (P for
      trend =.024) was no longer statistically significant after adjustment for age and
      sex (P for trend =.073). Conclusions: Strategies to prevent TDV in this
      population should not ignore the compounding negative effects of racial and
      gender discrimination.

PMID- 30116096
TI  - Anti-Racism Methods for Big Data Research: Lessons Learned from the HIV Testing,
      Linkage, & Retention in Care (HIV TLR) Study.
AB  - Public Health Critical Race Praxis (PHCRP) contributes three functional elements
      to health equity studies: a race conscious orientation; an antiracism lexicon
      based on Critical Race Theory (CRT); and an integrated, reflexive approach. Few
      big data studies employ all three functional elements. Therefore, this article
      describes the application of PHCRP to the Human Immunodeficiency Virus Testing,
      Linkage and Retention in care (HIV TLR) study (N=3,476,741), which connects
      multiple large datasets to electronic medical records to examine contextual
      determinants of racial/ethnic disparities in HIV care continuum outcomes in
      southern California. As HIV TLR demonstrates, PHCRP's innovative tools and
      strategies help big data research maintain fidelity to CRT.

PMID- 30116097
TI  - Commentary: Can Critical Race Theory Enhance the Field of Public Health? A
      Student's Perspective.
AB  - Critical race theory (CRT) is a body of work that seeks to understand and change
      the relationship between race, racism, and power. While relatively new to the
      health sciences, CRT is increasingly used as a conceptual framework to examine
      the role of racism in health inequalities. In this commentary, I outline ways in
      which CRT can also be used to enhance public health education, methodology, and
      practice.

PMID- 30116098
TI  - Developing a Medical School Curriculum on Racism: Multidisciplinary, Multiracial
      Conversations Informed by Public Health Critical Race Praxis (PHCRP).
AB  - Background: To fight racism and its potential influence on health, health care
      professionals must recognize, name, understand and talk about racism. These
      conversations are difficult, particularly when stakes feel high-in the workplace
      and in interracial groups. We convened a multidisciplinary, multi-racial group of
      professionals in two phases of this exploratory project to develop and pilot an
      intervention to promote effective dialogues on racism for first year medical
      students at the University of Minnesota Medical School. Methods: Informed by a
      Public Health Critical Race Praxis (PHCRP) methodology in Phase I, initial
      content was developed by a group of seven women primarily from racial and ethnic
      minority groups. In a later phase, they joined with five White (primarily male)
      colleagues to discuss racism and race. Participants met monthly for 12 months
      from Jan 2016-Dec 2016. All participants were recruited by study PI. An inductive
      approach was used to analyze meeting notes and post intervention reflections to
      describe lessons learned from the process of employing a PHCRP methodology to
      develop the aforementioned curriculum with a multidisciplinary and multi-racial
      group of professionals dedicated to advancing conversations on racial equity.
      Results: Participants from Phase I described the early meetings as "powerful,"
      allowing them to "bring their full selves" to a project that convened individuals
      who are often marginalized in their professional environments. In Phase II, which
      included White colleagues, the dynamics shifted: "...the voices from Phase I
      became quieter..."; "I had to put on my armor and fight in those later
      meetings...". Conclusions: The process of employing PHCRP in the development of
      an intervention about racism led to new insights on what it means to discuss
      racism among those marginalized and those with privilege. Conversations in each
      phase yielded new insights and strategies to advance a conversation about racism
      in health care.

PMID- 30116099
TI  - Commentary: Critical Race Theory Training to Eliminate Racial and Ethnic Health
      Disparities: The Public Health Critical Race Praxis Institute.
AB  - Racism is a fundamental cause of racial and ethnic disparities in health
      outcomes. Researchers have a critical role to play in confronting racism by
      understanding it and intervening on its impact on the health and well-being of
      minority populations. This requires new paradigms and theoretical frameworks that
      are responsive to structural racism's present-day influence on health, health
      disparities, and research. To address the complexity with which racism influences
      both health and the production of knowledge about minority populations, the field
      must accelerate the professional development of researchers who are committed to
      eliminating racial and ethnic health disparities and achieving health equity. In
      this commentary, we describe a unique and vital training experience, the Public
      Health Critical Race Praxis Institute at the University of Maryland's Center for
      Health Equity. Through this training institute, we have focused on the
      experiential knowledge of diverse researchers committed to examining racism and
      trained them on putting racism at the forefront of their research agendas. The
      Institute brought together investigators from across the United States, including
      junior and senior faculty as well as postdoctoral fellows. The public health
      critical race methodology was purposefully used to structure the Institute's
      curriculum, which instructed the scholars on Critical Race Theory as a framework
      in research. During a 2.5-day training in February 2014, scholars participated in
      activities, attended presentations, joined in reflections, and interacted with
      Institute faculty. The scholars indicated a strong desire to focus on race and
      racism and adopt a Public Health Critical Race Praxis framework by utilizing
      Critical Race Theory in their research.

PMID- 30116101
TI  - Examining the Timing of Women's Retirement in Urban China: A Discrete Time Hazard
      Rate Approach.
AB  - In spite of phenomenal wage growth in recent decades, female labor force
      participation in urban China has experienced a notable and puzzling decline,
      particularly so for women aged 40 and above. Concerns about women's status
      motivate an inquiry into the reasons behind the sharp drop, and consideration of
      how this decline may bear on their welfare. This paper estimates a probit model
      of labor force participation and a discrete time hazard rate model of retirement
      and non-retirement labor force withdrawals among urban married women aged 40 to
      51. The analysis uses data from a multi-province panel data set covering the
      interval from 1991 to 2011. The results inform policy discussions about pension
      system reform in the face of population aging and declining labor supply. In
      addition, recommendations are offered for policy measures that would increase
      women's labor force attachment, even as they approach their retirement horizon.

PMID- 30116100
TI  - SCHOOL-RELATED OUTCOMES FROM A RANDOMIZED CONTROLLED TRIAL OF ADOLESCENT
      DEPRESSION PREVENTION PROGRAMS.
AB  - Previous research has demonstrated the effectiveness of school-based depression
      prevention programs in reducing depressive symptoms and improving functioning.
      This study examined whether these programs have positive effects on school
      related outcomes. Students at 10 middle and high schools in New Jersey were
      randomized to weekly sessions of Interpersonal Psychotherapy - Adolescent Skills
      Training (IPT-AST) or group counseling (GC). Analyses examined whether there were
      intervention effects on participants' grades, attendance rates, and disciplinary
      outcomes over approximately one year post-intervention. Although there were no
      significant main effects of intervention condition, moderation analyses indicated
      more favorable effects of IPT-AST among certain higher-risk subgroups (e.g.,
      those from low-income families). Participants who experienced meaningful
      improvement in their depressive symptoms had significantly more positive outcomes
      on overall grades than those who did not experience meaningful improvement,
      regardless of intervention condition. Further research is needed to clarify the
      effects of depression prevention programs on these school-related outcomes.

PMID- 30116102
TI  - A Novel Approach for Identifying Relevant Genes for Breast Cancer Survivability
      on Specific Therapies.
AB  - Analyzing the genetic activity of breast cancer survival for a specific type of
      therapy provides a better understanding of the body response to the treatment and
      helps select the best course of action and while leading to the design of drugs
      based on gene activity. In this work, we use supervised and nonsupervised machine
      learning methods to deal with a multiclass classification problem in which we
      label the samples based on the combination of the 5-year survivability and
      treatment; we focus on hormone therapy, radiotherapy, and surgery. The proposed
      nonsupervised hierarchical models are created to find the highest separability
      between combinations of the classes. The supervised model consists of a
      combination of feature selection techniques and efficient classifiers used to
      find a potential set of biomarker genes specific to response to therapy. The
      results show that different models achieve different performance scores with
      accuracies ranging from 80.9% to 100%. We have investigated the roles of many
      biomarkers through the literature and found that some of the discriminative genes
      in the computational model such as ZC3H11A, VAX2, MAF1, and ZFP91 are related to
      breast cancer and other types of cancer.

PMID- 30116103
TI  - "Programmed Cell Death: A Process of Death for Survival" - How Far Terminology
      Pertinent for Cell Death in Unicellular Organisms.
AB  - Programmed cell death (PCD) is genetically regulated phenomenon of selective
      elimination of target cells that are either under pathological conditions or
      unwanted for organism's normal growth and development due to other reasons. The
      process although being genetically controlled is physiological in nature that
      renders some hallmarks like blebs in the cell membrane, lobe formation in nuclear
      membrane, DNA nicks resulting to DNA ladder of 200 bp, and downstream activation
      of caspases. Moreover, as the process refers to the death of "targeted cell", the
      term is exclusively suitable for multicellular organisms. Number of reports
      advocate similar type of cell death process in unicellular organisms. As cell
      death in unicellular organisms is also reflected by the signature of PCD obtained
      in metazoans, such cell death has been grouped under the broad category of PCD.
      It is pertinent to mention that by definition a unicellular organism is made of a
      single cell wherein it carries out all of its life processes. Using the term
      "Programmed Cell Death" with a preset "survival strategy of the organism" for
      unicellular organisms looks misnomer. Therefore, this correspondence argues and
      requests recommendation committee on cell death to revisit for the nomenclature
      of the cell death process in the unicellular organisms.

PMID- 30116104
TI  - Short-Term Outcomes of Treatment of Hip Osteoarthritis With 4 Bone Marrow
      Concentrate Injections: A Case Series.
AB  - The use of mesenchymal stem cells from bone marrow concentrate (BMC) has become
      an increasingly popular option as an alternative to total joint replacement.
      Although there is evidence to support the use of BMC injections to improve
      quality of life for patients with knee osteoarthritis (OA), there is limited
      evidence to support its use in patients with hip OA. This case series provides
      the short-term outcomes of 4 hip OA patients who each underwent 4 BMC injections.
      On average, the last follow-up was administered 3.5 months after the first
      injection. The results show that patients experienced decreased resting and
      active pain compared with baseline and mean 72.4% total overall improvement.
      Patients also reported less difficulty in performing daily activities following
      the procedure. These encouraging results warrant further research to better
      understand the effects of BMC injections on hip OA.

PMID- 30116105
TI  - Granular Cell Tumor Imaging Using Optical Coherence Tomography.
AB  - Background: Granular cell tumor (GCT) is a relatively uncommon tumor that may
      affect the skin. The tumor can develop anywhere on the body, although it is
      predominately seen in oral cavities and in the head and neck regions. Here, we
      present the results of optical coherence tomography (OCT) imaging of a large GCT
      located on the abdomen of a patient. We also present an analytical method to
      differentiate between healthy tissue and GCT tissues. Materials and methods: A
      multibeam, Fourier domain, swept source OCT was used for imaging. The OCT had a
      central wavelength of 1305 +/- 15 nm and lateral and axial resolutions of 7.5 and
      10 um, respectively. Qualitative and quantitative analyses of the tumor and
      healthy skin are reported. Results: Abrupt changes in architectures of the dermal
      and epidermal layers in the GCT lesion were observed. These architectural changes
      were not observed in healthy skin. Discussion: To quantitatively differentiate
      healthy skin from tumor regions, an optical attenuation coefficient analysis
      based on single-scattering formulation was performed. The methodology introduced
      here could have the capability to delineate boundaries of a tumor prior to
      surgical excision.

PMID- 30116107
TI  - The Effect of Short-Term Sport-Specific Strength and Conditioning Training on
      Physical Fitness of Well-Trained Mixed Martial Arts Athletes.
AB  - The purpose of the present study was to investigate the effect of a short-term,
      high-intensity, low-volume Mixed Martial Arts (MMA) specific strength and
      conditioning training program on performance in national level MMA athletes.
      Seventeen experienced fighters were divided into two groups: (A) Specific
      Training Group (STG; n = 10), which followed a specific strength and conditioning
      program designed according to the demands of MMA competition and (B) Regular
      Training Group (RTG; n = 7), in which participants followed a regular strength
      and conditioning program commonly used by MMA athletes. Before and after the four
      week training period (3 days per week), body composition, aerobic fitness,
      strength, power and speed were evaluated. Significant improvements in estimated
      VO2max, average power during the 2000 m rowing, bench press, back squat and
      deadlift 1RM, SJ power, CMJ height power, medicine ball throw velocity, 10 m
      sprint and 2 m take down speed and fat-free mass were found only in the STG (3.7
      to 22.2%; p < 0.05; Hedge's g = -0.42 - 4.1). No significant changes were found
      for the RTG (p = 0.225 to 0.811). Significant differences between the groups were
      found for almost all post-training assessments (p < 0.05; Hedge's g = 0.25 -
      1.45) as well as for the percentage changes from pre to post training (p < 0.05;
      Hedge's g: 0.25 - 1.45). Significant relationships were found between percentage
      changes in fat-free mass, endurance capacity, muscle strength/power and speed (r:
      -0.475 to 0.758; p < 0.05). These results suggest that a high-intensity low
      volume strength and conditioning training intervention designed according to the
      demands of MMA competition may result in significant performance improvements for
      well-trained fighters.

PMID- 30116106
TI  - Exercise Performance, Muscle Oxygen Extraction and Blood Cell Mitochondrial
      Respiration after Repeated-Sprint and Sprint Interval Training in Hypoxia: A
      Pilot Study.
AB  - This study aimed to investigate and compare the effects of repeated-sprint (RSH)
      and sprint interval training in hypoxia (SIH) on sea level running and cycling
      performance, and to elucidate potential common or divergent adaptations of muscle
      perfusion and -oxygenation as well as mitochondrial respiration of blood cells.
      Eleven team-sport athletes performed either RSH (3x5x10s, 20s and 5min recovery
      between repetitions and sets) or SIH (4x30s, 5min recovery) cycling training for
      3weeks (3 times/week) at a simulated altitude of 2,200m. Before and three days
      after the training period, a Wingate and a repeated cycling sprint test (5x6s,
      20s recovery) were performed with a 30min resting period between the tests. Four
      to five days after the training, participants performed a repeated running sprint
      test (RSA, 6x17m back and forth, 20s recovery) and a Yo-Yo intermittent recovery
      test (YYIR2) with 1 hour active recovery between tests. The order of the tests as
      well as the duration of the resting periods remained the same before and after
      the training period. During the cycling tests near-infrared spectroscopy was
      performed on the vastus lateralis. In four participants, mitochondrial
      respiration of peripheral blood mononuclear cells (PBMC) and platelets was
      measured before and after training. YYIR2 running distance increased by +96.7 +/-
      145.6 m after RSH and by +100.0 +/- 51.6 m after SIH (p = 0.034, eta2 = 0.449).
      RSA mean running time improved by -0.138 +/- 0.14s and -0.107 +/- 0.08s after RSH
      and SIH respectively (p = 0.012, eta2 = 0.564). RSH compared to SIH improved re
      oxygenation during repeated sprinting. Improvements in repeated cycling were
      associated with improvements in re-oxygenation (r = 0.707, p <0.05).
      Mitochondrial electron transfer capacity normalized per PBMC count was decreased
      in RSH only. This study showed that cycling RSH and SIH training improves sea
      level running performance. Our preliminary results suggest that RSH and SIH
      training results in different patterns of muscular oxygen extraction and PBMC
      mitochondrial respiration, without effect on platelets respiration.

PMID- 30116108
TI  - Is Plantar Loading Altered During Repeated Sprints on Artificial Turf in
      International Football Players?
AB  - We compared fatigue-induced changes in plantar loading during the repeated
      anaerobic sprint test over two distinct distance intervals. Twelve international
      male football outfield players (Qatar Football Association) completed 6 * 35-m
      sprints (10 s of active recovery) on artificial turf with their football boots.
      Insole plantar pressure distribution was continuously recorded and values (whole
      foot and under 9 foot zones) subsequently averaged and compared over two distinct
      distance intervals (0-17.5 m vs. 17.5-35 m). Sprint times increased (p <0.001)
      from the first (4.87 +/- 0.13 s) to the last (5.63 +/- 0.31 s) repetition,
      independently of the distance interval. Contact area (150 +/- 23 vs. 158 +/- 19
      cm2; -5.8 +/- 9.1%; p = 0.032), maximum force (1910 +/- 559 vs. 2211 +/- 613 N; 
      16.9 +/- 18.2%; p = 0.005) and mean pressure (154 +/- 41 vs. 172 +/- 37 kPa; 
      13.9 +/- 19.0%; p = 0.033) for the whole foot were lower at 0-17.5 m vs. 17.5-35
      m, irrespectively of sprint number. There were no main effects of sprint number
      or any significant interactions for any plantar variables of the whole foot. The
      distance interval * sprint number * foot region interaction on relative loads was
      not significant. Neither distance interval nor fatigue modified plantar pressure
      distribution patterns. Fatigue led to a decrement in sprint time but no
      significant change in plantar pressure distribution patterns across sprint
      repetitions.

PMID- 30116109
TI  - The Use of Generic and Individual Speed Thresholds for Assessing the Competitive
      Demands of Field Hockey.
AB  - The current study compared the running demands of professional field hockey
      players using individualized speed zones and generic default settings of the GPS
      manufacturer. In addition, the differences in slow, moderate and fast players
      were studied. Sixteen male players from the same club participated in the study
      (age: 25.5 +/- 2.9 years; body mass: 74.6 +/- 5.5 kg; stature 1.77 +/- 0.05 m).
      The peak speed of each participant was established at the end of the data
      collection period by analyzing all training and playing data throughout the
      season. Using players peak speed achieved for each participant during the season,
      individualized speed zones were retrospectively applied to all match-play data.
      Peak speed was used to categorize players into three groups, slow (5 players:
      29.2-30.2 km.h-1), moderate (6 players: 30.7-31.5 km.h-1) and fast (5 players:
      32.2-33.7 km.h-1). Significant differences were observed between generic and
      individual thresholds for the distance covered in moderate, high, and very high
      speed running in all positions (p = 0.01). Our findings show that the distances
      covered at high-speeds in midfielders and forwards were overestimated, while the
      very high-speed running and sprinting in backs were underestimated. Generic speed
      thresholds should be used if comparisons between positions is of importance.
      However, based on the different capacities of field hockey players, individual
      speed thresholds may be more suitable when addressing the relative stress on
      individual athletes.

PMID- 30116110
TI  - Effects of Plyometric Training on Neuromuscular Performance in Youth Basketball
      Players: A Pilot Study on the Influence of Drill Randomization.
AB  - The aim of this single-blind randomized controlled trial was to compare the
      effects of plyometric jump training (PJT), with (RG) and without (NRG) between
      session drill randomization, on performance measures (i.e., jumping and sprinting
      abilities, change of direction speed, and technical performance) in youth male
      basketball players (age, 10.2 +/- 1.7 years), assigned to either the NRG (n = 7),
      RG (n = 6), or control group (n = 6). Before and after the intervention,
      countermovement jump, 20-cm drop jump, 30-m sprint (with or without ball
      dribbling), and change-of-direction speed tests were completed. The PJT was
      applied twice per week for seven weeks. The only difference between PJT groups
      was the order of drill execution. An ANOVA was used to detect differences between
      study groups. The analyses revealed significant main effects of time (all p<.01;
      d = 0.64-0.89) and group x time interaction (all p<.05; d=0.31-51) for all
      examined variables. Post hoc analyses revealed moderate-large significant
      improvements for the RG (countermovement jump: 18.8%, d = 0.6; 20-cm drop jump:
      23.9%, d = 0.80; 30-m sprint: 11.6%, d = 1.13; 30-m sprint with ball dribbling:
      9.3%, d = 0.54; change of direction speed test: 14.6%, d = 1.82). In contrast,
      post hoc analyses revealed only small improvements for the NRG (20-cm drop jump:
      14.1%, d = 0.36; 30-m sprint: 6.8%, d = 0.45; 30-m sprint with ball dribbling:
      8.8%, d = 0.35; change of direction speed test: 10.5%, d = 0.49). Application of
      PJT without randomization is effective for improving physical and technical
      qualities. However, PJT could be more beneficial when executed with between
      session randomization of drills.

PMID- 30116111
TI  - Effects of Spatiotemporal Constraints and Age on the Interactions of Soccer
      Players when Competing for Ball Possession.
AB  - Although there are several descriptions of interpersonal coordination in soccer
      teams, little is known about how such coordination is influenced by space and
      time constraints. In this study, we analyzed variations in interpersonal
      coordination under different marking intensities and across different age groups.
      Marking intensity was manipulated by changing the players' game space and time of
      ball possession in a conditioned soccer game known as rondo. Five participants in
      each age category (U13, U15, U17, and U20) performed rondo tasks in four
      experimental conditions, in a total of 134 trials. The dependent variables
      considered were pass performance and eco-physical variables capturing the player
      environment coupling, such as coupling of the marking between players. Our
      results demonstrate that in soccer: (1) markers and passers are tightly coupled;
      (2) the marker-passer coupling emerges from a flexible and adaptive exchange of
      passes; (3) the marker-passer coupling is stronger in markings of higher
      intensity and older age groups. Thus, the interactions between soccer players in
      marking can be analyzed as an emerging and self-organized process in the context
      of group performance.

PMID- 30116112
TI  - Effect of Compression Garments on the Development of Edema and Soreness in
      Delayed-Onset Muscle Soreness (DOMS).
AB  - Delayed-onset muscle soreness (DOMS), an ultrastructural muscle injury, is one of
      the most common reasons for impaired muscle performance. The purpose of this
      study was to investigate the influence of sport compression garments on the
      development of exercise-induced intramuscular edema in the context of DOMS. DOMS
      was induced in 15 healthy participants. The participants performed a standardized
      eccentric exercise of the calf muscles. Magnetic resonance imaging (MRI) was
      performed at baseline and 60h after exercise (T2-weighted signal intensity and T2
      relaxation time was evaluated in each compartment and the intramuscular edema in
      the medial head of the gastrocnemius muscle was segmented). After the exercise, a
      conventional compression garment (18-21 mmHg) was placed on one randomized calf
      for 60h. The level of muscle soreness was evaluated using a visual analogue pain
      scale. T2-weighted signal intensity, T2 relaxation time and intramuscular edema
      showed a significant interaction for time with increased signal
      intensities/intramuscular edema in the medial head of the gastrocnemius muscle at
      follow-up compared to baseline. No significant main effect for compression or
      interaction between time and limb occurred. Further, no significant differences
      in the soleus muscle and the lateral head of the gastrocnemius muscle were noted
      between limbs or over time. After exercise, there was significantly increased
      muscle soreness in both lower legs in resting condition and when going downstairs
      and a decreased range of motion in the ankle joint. No significant difference was
      observed between the compressed and the non-compressed calf. Our results indicate
      that wearing conventional compression garments after DOMS has been induced has no
      significant effect on the development of muscle edema, muscle soreness, range of
      motion and calf circumference.

PMID- 30116113
TI  - Modelling the HRV Response to Training Loads in Elite Rugby Sevens Players.
AB  - A systems modelling approach can be used to describe and optimise responses to
      training stimuli within individuals. However, the requirement for regular maximal
      performance testing has precluded the widespread implementation of such modelling
      approaches in team-sport settings. Heart rate variability (HRV) can be used to
      measure an athlete's adaptation to training load, without disrupting the training
      process. As such, the aim of the current study was to assess whether chronic HRV
      responses, as a representative marker of training adaptation, could be predicted
      from the training loads undertaken by elite Rugby Sevens players. Eight
      international male players were followed prospectively throughout an eight-week
      pre-season period, with HRV and training loads (session-RPE [sRPE] and high-speed
      distance [HSD]) recorded daily. The Banister model was used to estimate vagally
      mediated chronic HRV responses to training loads over the first four weeks
      (tuning dataset); these estimates were then used to predict chronic HRV responses
      in the subsequent four-week period (validation dataset). Across the tuning
      dataset, high correlations were observed between modelled and recorded HRV for
      both sRPE (r = 0.66 +/- 0.32) and HSD measures (r = 0.69 +/- 0.12). Across the
      sRPE validation dataset, seven of the eight athletes met the criterion for
      validity (typical error <3% and Pearson r >0.30), compared to one athlete in the
      HSD validation dataset. The sRPE validation data produced likely lower mean bias
      values, and most likely higher Pearson correlations, compared to the HSD
      validation dataset. These data suggest that a systems theory approach can be used
      to accurately model chronic HRV responses to internal training loads within elite
      Rugby Sevens players, which may be useful for optimising the training process on
      an individual basis.

PMID- 30116114
TI  - The Relative Age Effect in the 10 Best Leagues of Male Professional Football of
      the Union of European Football Associations (UEFA).
AB  - The aim of the present research was to observe the relative age effect on
      professional soccer players of the ten best leagues of the Union of European
      Football Associations (UEFA), according to the IFFHS (International Federation of
      Football History and Statistics). The sample consisted of 5201 professional
      players who participated in the professional leagues during the 2016-2017 season.
      The birth date of each player was classified in four quartiles (Q1, Q2, Q3 and
      Q4). The frequencies (fr) and percentages (%) of the birth quartiles were
      analyzed. The chi square test (X2) and degrees of freedom (gl) were performed to
      check the differences in the intergroup distribution. Likewise, odd ratios were
      calculated for the different quartiles, where Q4 was the reference group
      according to the different leagues studied, playing positions (goalkeeper,
      defender, midfielder and forward) and classification (first four places, half-of
      the table and four last places). To calculate the size of the effect on the
      nominal variables, the Cramer V test was carried out. The results confirmed a
      greater representation of players born in Q1 and Q2, indicating statistically
      significant values (p < 0.05) for all the leagues studied, except in the Eerste
      Klasse A (Belgium). This significance was repeated for the demarcation variables
      in the field, with a greater effect in the case of the midfielders. Finally, the
      RAE also affected the three groups according to teams' classification. The
      conclusions confirm the effect of the RAE in the sample studied, which would
      require a review of the talent selection processes in football in order to
      balance the chances of success of players born at the end of the year.

PMID- 30116116
TI  - Feasibility and Effects of Structured Physical Exercise Interventions in Adults
      with Relapsing-Remitting Multiple Sclerosis: A Pilot Study.
AB  - Multiple sclerosis (MS) is a chronic neurological disease which affects young
      adults at a time of maximum personal, professional and social growth. Recent
      guidelines on physical activity have established that exercise is an essential
      component of the clinical management of people with MS with mild or moderate
      degree of disability. The main purpose of this study was to test the feasibility
      and the effects of two different 40-week structured physical exercise
      interventions (a supervised high intensity interval training plus home exercise
      program and a self-applied home-based exercise program) on clinical evolution,
      psychological wellbeing, quality of life, fatigue, cardiorespiratory fitness,
      strength and balance of people with MS. Twenty-nine participants with relapsing
      remitting MS (RRMS) participated in this study. All of them were fully ambulatory
      and with minimal disability (Expanded Disability Status Scale <3), for at least
      the last six months. Participants selected to be part of a combined face-to-face
      plus home exercise group (CFTFG; n = 8); a self-applied home-based exercise group
      (HG; n = 11) or a control group (CG; n = 10). A total of 23 participants
      completed the protocol (79.3%), of which 8 participants (100%) from the CFTFG, 7
      (63.6%) from the HG and 8 (80%) from the CG. During the first 20-weeks of
      training, adherence from the CFTFG reached 77.5% and from the HG reached 50 %.
      During the second 20-weeks of training, adherence from the CFTFG reached 62.5%
      and from the HG reached 45.4%. After 20-weeks of training, a significant
      improvement in the absolute VO2 peak and in the 30-second sit to stand test was
      observed in the CFTFG (all p < .05). This study confirms that offering a 40-week
      structured exercise programme to a group of fully ambulatory and minimally
      disabled persons with RRMS is feasible and safe. Any adverse event related to the
      trial was reported by the participants.

PMID- 30116117
TI  - Moral Disengagement and Student Misbehavior in Physical Education.
AB  - This study examined how mechanisms of moral disengagement (MD) were related to
      students' self-reported misbehaviors. Participants were 282 and 336 high school
      students enrolled in physical education classes. In Stage 1, results of
      regression analysis showed that advantageous comparison and non-responsibility
      positively predicted four misbehaviors (i.e., low engagement, failure to follow
      directions, poor self-management, and distracting behavior). In Stage 2, results
      of the structural equation modeling confirmed that advantageous comparison and
      non-responsibility were the significant predictors of student misbehavior in
      physical education. It is suggested that prevention and intervention programs
      should address students' advantageous comparison (e.g., compared to skipping
      class, it is not a big deal to be shirking in class) and non-responsibility
      (e.g., no one is taking the class seriously; I am just one of them) to reduce
      misbehaviors in the physical education context.

PMID- 30116115
TI  - Impact-Induced Muscle Damage: Performance Implications in Response to a Novel
      Collision Simulator and Associated Timeline of Recovery.
AB  - The implications of impact-induced muscle damage (IIMD) that results from
      participation in contact-sport are not well understood. The purpose of the
      present study was to implement a novel method of generating IIMD and characterise
      the implications of this on perceptual, biochemical and exercise performance
      parameters. Eighteen male recreational contact-sport athletes completed a single
      group time series with measures assessed at baseline (PRE) and immediately
      following (POST) an IIMD protocol, with repeat testing 24, 48, and 72 h following
      the IIMD protocol. Biochemical indices of muscle damage (myoglobin [Mb]) and
      inflammation (high-sensitivity C-reactive protein [hs-CRP]), 15 m sprint
      performance, squat jump peak power (SJ-PP), and perceived soreness were compared
      to PRE using a one-way (time) repeated measures ANOVA with post-hoc t tests.
      Speed over 5 and 15 m were impaired for 48 h (7.5 +/- 4%, p < 0.01) and SJ-PP was
      impaired for 48 h following the IIMD protocol (9.5 +/-3 %, p < 0.01). Subjective
      soreness was elevated from baseline for 72 h (P < 0.01) following the IIMD
      protocol. No change in [CRP] or [Mb] was observed (p > 0.01). IIMD resulted in
      impaired ability to produce power and speed, whilst negatively influencing
      perceived soreness. These changes were most pronounced in the 48 h following the
      IIMD protocol. No change in muscle damage or inflammation indices were observed,
      primarily due to the highly variable response. Thus, the experimental protocol
      used in the present study may be used as a model to further investigate other
      aspects of IIMD.

PMID- 30116118
TI  - Comparison of Proprioceptive Training and Muscular Strength Training to Improve
      Balance Ability of Taekwondo Poomsae Athletes: A Randomized Controlled Trials.
AB  - Maintaining balance while performing "Hakdariseogi" in Taekwondo, which involves
      standing on one leg, is a critical aspect of the Poomsae competition. The purpose
      of this study was to investigate the effect of proprioceptive training and lower
      limb muscular strength training on the balance of Taekwondo Poomsae athletes over
      a 6-week period. Thirty Taekwondo Poomsae athletes were randomly assigned to
      three groups, namely, a proprioception training group, a lower-limb muscular
      strength training group, and a control group. Biomechanics data were collected
      using eight infrared cameras (Qualysis, Sweden) at 200 Hz and a force plate
      (Kistler, Switzerland) at 2,000 Hz while the participants performed
      "Hakdariseogi" before and after the 6-week intervention. Balance and stability
      variables were calculated using customized MATLAB R2014b software (Mathworks,
      Inc., USA). The medio-lateral (M/L) center of pressure (CoP) range, M/L CoP mean
      velocity, antero-posterior (A/P) CoP range, A/P CoP mean velocity, and the
      vertical ground reaction torque after the training were reduced at P1 in the PG
      groups (p < 0.05). A decrease in the A/P CoP range, A/P CoP mean velocity, and
      vertical ground reaction torque after the training were observed at P2 in the PG
      and SG groups (p < 0.05). The PG exhibited a smaller A/P CoP range and A/P CoP
      mean velocity, in comparison to CG (p < 0.05). The A/P CoP position at P1 was
      negatively correlated with the vertical ground reaction torque, A/P CoP range,
      and A/P CoP mean velocity at P2(r = -0.438, r = -0.626, r = -0.638). Based on the
      above results, this study determined that both proprioception training and lower
      extremity muscle strength training resulted in an improvement of athletic
      performance. It was also desirable to move the CoP position through conscious
      effort forward at P2 in order to maintain the crane stance without sway.

PMID- 30116119
TI  - Somatotype Hormone Levels and Physical Fitness in Elite Young Soccer Players over
      a Two-Year Monitoring Period.
AB  - The effect of two soccer-training seasons on the growth, development and
      somatotype hormone concentrations of elite youth soccer players were evaluated.
      Eighteen elite soccer players and 18 age-matched non-athletic control subjects
      participated in the study. Anthropometric-measurements, aerobic and anaerobic
      performance tests and serum concentrations of insulin-like growth factor-1 (IGF
      1), insulin-like growth factor binding protein-3 (IGFBP-3), and growth hormone
      (GH) were assessed at 5 time points across two competitive seasons. Soccer
      players revealed higher GH, IGF-1 and IGFBP-3 than the control group across all
      time points. Significant moderate correlations were observed only in soccer
      players between hormonal concentrations (IGF-1 and IGFBP-3) and the jumping tests
      (r = 0.45-0.48; p < 0.01). Somatotropic axis hormones, anthropometric and
      physical parameters increased to a greater degree with growth and soccer training
      combined compared to growth alone. Results from this investigation revealed that
      intense training did not impair growth or development in these young soccer
      players across 2-year period.

PMID- 30116120
TI  - Validation of A New Judo-Specific Ergometer System in Male Elite and Sub-Elite
      Athletes.
AB  - Our experimental approach included two studies to determine discriminative
      validity and test-retest reliability (study 1) as well as ecological validity
      (study 2) of a judo ergometer system while performing judo-specific movements.
      Sixteen elite (age: 23 +/- 3 years) and 11 sub-elite (age: 16 +/- 1 years)
      athletes participated in study 1 and 14 male sub-elite judo athletes participated
      in study 2. Discriminative validity and test-retest reliability of sport-specific
      parameters (mechanical work, maximal force) were assessed during pulling
      movements with and without tsukuri (kuzushi). Ecological validity of muscle
      activity was determined by performing pulling movements using the ergometer
      without tsukuri and during the same movements against an opponent. In both
      conditions, electromyographic activity of trunk (e.g., m. erector spinae) and
      upper limb muscles (e.g., m. biceps brachii) were assessed separately for the
      lifting and pulling arm. Elite athletes showed mostly better mechanical work,
      maximal force, and power (0.12 <= d <= 1.80) compared with sub-elite athletes.
      The receiver operating characteristic analysis revealed acceptable validity of
      the JERGo(c) system to discriminate athletes of different performance levels
      predominantly during kuzushi without tsukuri (area under the curve = 0.27-0.90).
      Moreover, small-to-medium discriminative validity was found to detect meaningful
      performance changes for mechanical work and maximal force. The JERGo(c) system
      showed small-to-high relative (ICC = 0.37-0.92) and absolute reliability (SEM =
      10.8-18.8%). Finally, our analyses revealed acceptable correlations (r = 0.41
      0.88) between muscle activity during kuzushi performed with the JERGo(c) system
      compared with a judo opponent. Our findings indicate that the JERGo(c) system is
      a valid and reliable test instrument for the assessment and training of judo
      specific pulling kinetics particularly during kuzushi movement without tsukuri.

PMID- 30116121
TI  - Efficacy of Exercise Therapy in Persons with Burnout. A Systematic Review and
      Meta-Analysis.
AB  - An increasing amount of scientific work suggests positive effects of exercise
      related interventions in patients with burnout. Exercise therapy could therefore
      be a useful intervention procedure in the treatment of burnout. The aim of this
      meta-analysis is to examine empirical findings for exercise therapy used to treat
      burnout in the occupational setting, including the variety of the application and
      variety of the exercise modality itself. Electronic databases (PubMed, Cochrane
      Library, Scopus, PubPsych, PsycInfo) were searched (January 2018) for randomized
      controlled trials reporting on exercise therapy intervention studies in persons
      with burnout. The burnout scores from the various measurement instruments as well
      as standardized mean differences (SMDs) with 95% confidence intervals (CI) were
      calculated and seen as the main outcomes and measures. Four out of six studies
      with a total sample of 248 participants could be used for meta-analysis. A
      statement on the combined effect size can only be made with caution due to the
      length of the confidence interval of [-0.41; 0.09]. With an I2 value of 0%, no
      heterogeneity is present in this meta-analysis. Ultimately there was no clear
      difference found between intervention and control conditions. This paper does not
      support the widespread assumption that exercise therapy seems to be a successful
      means to alleviate burnout symptoms. However, the different types of physical
      activity and treatment modalities used in the included studies impede clear
      conclusions. Future studies should deal with the specific efficacy of different
      exercise modalities and their combination with further cognitive behavioural or
      mindfulness-based interventions.

PMID- 30116122
TI  - Effects of Half-Time Cooling Using A Cooling Glove and Jacket on Manual Dexterity
      and Repeated-Sprint Performance in Heat.
AB  - This study aimed to assess the separate and combined effects of a cooling glove
      (CG) and a gel-cooling jacket (CJ) used during a half-time break on manual
      dexterity performance (Purdue Pegboard test) and subsequent repeat-sprint cycling
      performance in hot conditions. Twelve male athletes performed four experimental
      trials (within subjects, counterbalanced design) that consisted of: wearing a CG,
      wearing a CJ, combination of CG and CJ (CG+J) or a no-cooling control (NC) for 15
      min during a 20 min half-time break performed between 2 x 30 min repeated-sprint
      cycling bouts in heat (35.0 +/- 1.2 degrees C and 52.5 +/- 7.4% RH). Manual
      dexterity (dominant and non-dominant hand) was assessed immediately before and
      after the first-half of exercise, then immediately after cooling and the second
      half of exercise. No differences were found for manual dexterity performance
      between trials or over time (p > 0.05). Additionally, no differences were found
      for power and work performance variables assessed during the second-half of
      exercise (p > 0.05), however participants felt 'cooler' wearing CG+J compared to
      NC (Thermal Sensation scale; p = 0.041). Further, no differences were found
      between trials for changes in gastrointestinal core temperature for any time
      period assessed (p > 0.05). In conclusion, the cooling trials did not affect
      manual dexterity or second-half repeated-sprint cycling performance compared to
      NC.

PMID- 30116123
TI  - Injuries among Korean Female Professional Golfers: A Prospective Study.
AB  - This study aims to analyze the incidence, location, type, and mechanisms of
      injuries and possible injury risk factors among all levels of Korean female
      professional golfers. This was a prospective study with a follow-up period of 24
      months. A total of 363 members of the Korean Ladies Professional Golf Association
      (KLPGA), who competed in tournaments during the 2015 and 2016 seasons, took part
      in the study. The incidence of injury varied by tournament level and was
      significantly higher in Division II (11.1/1000AEs) and Division III
      (13.4/1000AEs) than in Division I (5.6/1000AEs) (p < 0.05). The most common
      location and type of injury were the shoulder/clavicle (Division I: 14.1%,
      Division II: 15.7%, Division III: 17.3%) and the tendinosis or tendinopathy
      (21.2%) (Division I: 23.7%, Division II: 21.2%, Division III: 18.5%),
      respectively. The most common mechanism of injury was the golf swing (47.9%-51.6%
      for the three divisions), and the most frequent specific phase of injury was upon
      ball impact (23.5%-30.9%). Multivariate analysis revealed that body mass index
      and the number of previous season competitions were significantly associated with
      injury risk in female golfers. The other factors examined did not have a
      significant association with golf-related injuries. In conclusion, KLPGA golfers
      were commonly exposed to injuries and showed a higher rate of injuries in
      competitions than practices, with significantly higher in Division II, III than
      Division I. However, overall, there was no significant difference in the
      location, type, mechanism and risk factors for injuries among the division level
      of KLPGA.

PMID- 30116124
TI  - The Effects of Acute Low-Volume HIIT and Aerobic Exercise on Leukocyte Count and
      Redox Status.
AB  - A single bout of exercise can result in inflammatory responses, increased
      oxidative stress and upregulation of enzymatic antioxidant mechanisms. Although
      low-volume high-intensity interval training (HIIT) has become popular, its acute
      responses on the above mechanisms have not been adequately studied. The present
      study evaluated the effects of HIIT on hematological profile and redox status
      compared with those following traditional continuous aerobic exercise (CET).
      Twelve healthy young men participated in a randomized crossover design under HIIT
      and CET. In HIIT session, participants performed four 30-sec sprints on a cycle
      ergometer with 4 min of recovery against a resistance of 0.375 kg/kg of body
      mass. CET consisted of 30-min cycling on a cycle-ergometer at 70% of their
      VO2max. Blood was drawn at baseline, immediately post, 24h, 48h and 72h post
      exercise and was analyzed for complete blood count and redox status
      (thiobarbituric acid reactive substances, [TBARS]; protein carbonyls, [PC]; total
      antioxidant capacity, [TAC]; catalase and uric acid). White blood cells (WBC)
      increased after both exercise protocols immediately post-exercise (HIIT: 50% and
      CET: 31%, respectively). HIIT increased (+22%) PC post-exercise compared to
      baseline and CET (p < 0.05). HIIT increased TAC immediately post-exercise (16%)
      and at 24h post-exercise (11%, p < 0.05), while CET increased TAC only post
      exercise (12%, p < 0.05) compared to baseline, and TAC was higher following HIIT
      compared to CET (p < 0.05). Both HIIT and CET increased uric acid immediately
      post- (21% and 5%, respectively, p < 0.05) and 24h (27% and 5%, respectively, p <
      0.05) post-exercise and the rise was greater following HIIT (p < 0.05). There
      were no significant changes (p > 0.05) for TBARS and catalase following either
      exercise protocol. Low-volume HIIT is associated with a greater acute phase
      leukocyte count and redox response than low-volume CET, and this should be
      considered when an exercise training program is developed and complete blood
      count is performed for health purposes.

PMID- 30116125
TI  - Relationship Between Electromyogram Spectrum Parameters and the Tension-Time
      Index During Incremental Exercise in Trained Subjects.
AB  - The inspiratory muscle tension-time index TT0.1 (given by P0.1/PImax x TI/TTOT)
      could be used to reliably assess inspiratory muscle activity during exercise. So
      far, the correlation between the TT0.1 and diaphragmatic activity has not been
      measured and the TT0.1 has not been compared with other measurements of the
      inspiratory muscle load such as the transdiaphragmatic pressure index or TTdi. In
      this study we hypothesize that the TT0.1 measuring the mouth is a noninvasive
      reflection of the electromyographic activity of the diaphragm. We simultaneously
      measured TT0.1 and surface EMG (SEMG) of 8 trained subjects at rest and during
      incremental exercise. The curvature of TT0.1 and the root mean square (RMS)
      follow the same trend during the incremental exercise with a significant
      correlation between TT0.1 and surface EMG parameters (RMS; r = 0.81 p < 0.001 and
      MPF; r = 0.80 p < 0.001 respectively). We conclude that TT0.1 measured as s an
      adequate noninvasive method reflects the diaphragmatic activity during
      incremental exercise in healthy subjects.

PMID- 30116127
TI  - Is there any association between adenoid biofilm and upper airway infections in
      pediatric patients?
AB  - Aim: To evaluate the association of the presence and extent of adenoid biofilms
      and the frequency of upper airway infections in children with upper airway
      obstruction. Material and Methods: This cross-sectional study was conducted from
      October 2014 to December 2015 on pediatric patients who were candidates for
      adenoidectomy due to obstructive sleep apnea. After removal of the adenoid tissue
      and fixation in 2.5% glutaraldehyde, the samples were sent to the electron
      microscopy unit. The extent of biofilm formation was examined using environmental
      scanning electron microscopy. These results were then confirmed using image
      analysis software. Results: Fifty-seven children with a mean age of 7.31 (+/
      2.65) years were included in the study. Forty-three (75.4%) were male and 14
      (24.6%) were female. The average number of upper airway infections during the
      last 12 months before adenoidectomy was 10.01 (+/-5.38). Biofilm structures were
      detected in all (100%) samples. As the main outcome, the extent of biofilm
      grading exhibited a statistically significant correlation with the frequency of
      upper airway infections (p<0.001). There was no significant correlation between
      sex and adenoid size with the biofilm extent. Conclusion: The present study
      showed that the extent of adenoid biofilm had a significant relationship with the
      frequency of upper airway infection rate. It seems that the presence of a biofilm
      on the adenoid surface as a reservoir for microorganisms could cause chronic
      inflammation.

PMID- 30116126
TI  - Respiratory syncytial virus infections in neonates and infants.
AB  - Respiratory syncytial virus is one of the major causes of respiratory tract
      infections during infancy with high rates of hospitalization and mortality during
      the first years of life. It is the most common cause of acute bronchiolitis and
      viral pneumonia in children below two years of age and second the most common
      cause of postneonatal infant mortality all around the world following malaria. In
      addition, the virus has been causally linked to recurrent wheezing and associated
      with pediatric asthma. The respiratory syncytial virus infections tend to be
      severe in high risk patients such as patients below six months of age, with
      prematurity, congenital heart diseases, neuromuscular diseases and immune
      deficiencies. No specific treatment is available for respiratory syncytial virus
      infections to date. Severe cases require supportive therapy, mainly oxygen
      supplementation and hydration, and less frequently, ventilatory support. Because
      there is no vaccine to prevent respiratory syncytial virus infections or
      clinically effective treatment to administer to children with respiratory
      syncytial virus infection, immunoprophylaxis with palivizumab is currently the
      only method for reducing morbidity associated with severe respiratory syncytial
      virus in high-risk infants.

PMID- 30116128
TI  - Life quality of children with congenital heart diseases.
AB  - Aim: We aimed to evaluate the effects of the severity and symptoms of congenital
      heart disease and the emotional and behavioral problems of affected children on
      their quality of life. Material and Methods: The study was performed by
      interviewing 80 children aged between 6 and 16 years (40 with cyanotic heart
      disease and 40 with acyanotic disease) and their mothers. A sociodemographic data
      form, quality of life questionnaire, strength and difficulties questionnaire, and
      family life and parenting attitudes scale were used in the research. Life quality
      was the dependent variable of this research. Results: No significant relation was
      found between age, sex, and education level of the parents and all quality of
      life subscale scores (p>0.05). In terms of quality of life, total quality of life
      subscale, emotional well-being and self-esteem subscales were significantly lower
      in children with cyanotic congenital heart disease (p=0.02, p=0.007, p=0.006,
      respectively). The total quality of life subscale was significantly lower in
      children with a medical treatment and surgical history. In terms of clinical
      symptoms, self-esteem, friendship and school life quality subscales were affected
      in the presence of dyspnea. As scores from strength and difficulties
      questionnaire increased, which is used for the assessment of children's
      psychological symptoms, all quality of life scores were significantly lowered
      except for school and family subscales. Conclusion: It was found that symptoms of
      congenital heart disease affected the psychosocial quality of life subscales
      rather than the physical subscales. In addition, it was observed that mental
      symptoms in both the mother and child negatively affected quality of life rather
      than disease-related parameters.

PMID- 30116129
TI  - Out-of-hospital deliveries: A case-control study.
AB  - Aim: To identify the factors, risks, and mortality associated with unplanned out
      of-hospital births. Material and Methods: This observational, retrospective, case
      control study was conducted between 2005 and 2013 through a review of medical
      records from the hospital network of a county of Brazil. Mother-child dyads were
      divided into in-hospital births and unplanned out-of-hospital births. For
      hypothesis testing involving quantitative variables, parametric and nonparametric
      methods (t-test or Mann-Whitney test, respectively) were used as appropriate
      after ascertaining normality of distribution via the Kolmogorov-Smirnov or
      Shapiro-Wilk tests. The chi-square test, Fisher's exact test, odds ratios, and
      95% confidence intervals were used to assess the relationship between categorical
      variables. A binary logistic regression was applied for pooled analysis of those
      variables that, when analyzed in isolation, had significant p-values on
      hypothesis testing. In all tests, p-values <0.05 were considered statistically
      significant. Results: Of the 420 records, 117 corresponded to out-of-hospital
      births dyads. Mothers were predominantly nonwhite (p<0.001), with a history of
      inadequate antenatal care (p<0.001), multiparous (p<0.001), aged >25 years
      (p=0.031), and had more puerperal complications (p<0.001). Their newborns had low
      birth weight (Odds Ratios: 2.22; 95% CI: [1.4-3.4]; p<0.001), higher morbidity
      (p=0.009), a higher rate of admission to neonatal intensive care and stepdown
      units (p=0.030), and prolonged length of stay (p<0.001). Conclusion: The risk of
      maternal and neonatal complications, as well as the neonatal mortality rate, were
      higher for unplanned out-of-hospital deliveries. It occurred predominantly in
      nonwhite, older, multiparous women who had received incomplete antenatal care and
      who lived far from perinatal care centers.

PMID- 30116131
TI  - Distribution of childhood skin diseases according to age and gender, a single
      institution experience.
AB  - Aim: Studies on pediatric skin diseases in Turkey are not yet sufficient. It was
      aimed to characterize the prevalence of skin diseases, age and gender
      distribution in children living in the Erzincan region. Material and Methods:
      10,115 children aged 0-16 years who reached to our outpatient clinic between
      01.11.2014 and 30.11.2016 were included in the study. The frequency, age and
      gender distribution of the skin diseases were examined. The cases were divided
      into 4 groups; infantile period (0-2 years), preschool period (3-5 years), school
      period (6-11 years) and adolescence period (12-16 years). Skin diseases were
      categorized in 10 groups. A total of 148 skin diseases were identified. Results:
      5376 of the patients were female (%53.14) and 4739 were male (%46.86). The most
      common disease groups are; infectious diseases (24.62%), eczema (21.95%),
      acne&follicular diseases (18.45%) and allergic skin diseases (11.02%). The most
      common diseases were acne vulgaris (17.82%), warts (10.03%) and irritant contact
      dermatitis (9.42%). The most common skin diseases in regard of different age
      groups are; contact dermatitis in the 0-2 years and 3-5 years age groups, warts
      in the 6-11 years age group, and acne vulgaris in 12-16 years age group.
      Conclusion: Most common diseases in our study are diseases that can be reduced by
      preventive health care and health education programs. There is a need for broad
      based epidemiological studies in this area to establish preventive health care
      policies and to develop education programs.

PMID- 30116130
TI  - Investigation of the factors affecting mother's exclusive breastfeeding for six
      months.
AB  - Aim: The aim of this study is to investigate the socio-demographic
      characteristics and psychopathologic features of mothers living in Cukurova,
      Adana and to investigate the effect of these characteristics on exclusive
      breastfeeding status for the first six months. Material and Methods: This is a
      cross sectional study. 284 randomly selected women were reached in the study,
      between November 2015-February 2016. A questionnaire consisting of 27 questions
      which determine sociodemographic characteristics and brief symptom inventory were
      applied. As for the statistical evaluation, SPSS 19 Package Software for Windows
      was used. For the statistical analysis; frequency tables, average scores from the
      brief symptom inventory, chi square test, Mann-Whitney U and Multiple logistic
      regression analysis were used. Results: 37.0% of the mothers gave exclusive
      breastfeeding for first six months. Those who graduated from high school and
      upper school, those who were educated in breastfeeding, those who breastfed for
      the half hour after birth, and those who did not work had a significantly higher
      rate of giving only breast milk for the six months. However, the rate of
      breastfeeding in first six months was significantly lower for women those who
      lived together with their elders and smokers. The mean scores from brief symptom
      inventory were significantly higher in mothers who did not give breast milk only
      during first six months. Conclusion: Exclusive breastfeeding rate was 37% in the
      first six months of our study. The postpartum period is a period in which the
      risk of psychiatric discomfort increases and the mother should be supported.

PMID- 30116132
TI  - Liver transplantation from a live donor to a patient with maple syrup urine
      disease: Two case reports.
AB  - Liver transplantation were reported in patients with classic maple syrup urine
      disease in the literature. Branched chain alpha keto acid dehydrogenase activity
      can be improved in patients after transplant, and a protein-restricted diet is
      usually not needed. The first patient was a boy aged 2,5 years who presented with
      frequent ketosis attacks and epileptic seizures, and the second patient was an 11
      month-old boy who also presented with frequent ketosis episodes, both despite
      adherence to diet therapy. Both patients received liver transplantations from
      live donors. A low protein diet was no longer required and no decline in
      cognitive functions was observed in either patient in the follow-up. We wanted to
      present these cases to show that despite a normal diet, plasma levels of branched
      chain amino acids remained normal without any decline in cognitive function
      after liver transplantation in patients with classic maple syrup urine disease
      patients.

PMID- 30116133
TI  - Pulmonary hydatid cyst disease mimicking necrotizing pneumonia in a child with
      leukocytoclastic vasculitis.
AB  - The diagnosis and management of pulmonary hydatid cyst disease represents an
      important clinical problem in countries of the world that are endemic to
      echinococcal infection. Atypical clinical and radiologic findings including
      multiple cavitary lesions in the lung and pleural effusion may lead to
      misdiagnosis or delay in diagnosis in these patients. We report a patient who was
      followed up in our hospital with rashes and, clinical and radiologic findings of
      necrotizing pneumonia in whom there was no response to broad spectrum
      antibiotherapy. Lung computed tomography showed multiple thick-walled cystic
      lesions and pleural effusion and the diagnosis of pulmonary hydatid cyst disease
      was confirmed by surgical and serologic examinations. Antibiotic treatment was
      changed to albendazole 10 mg/kg/day. There was no liver involvement in terms of
      cyst hydatid disease with ultrasonographic examination. Skin biopsy showed
      leukocytoclastic vasculitis. Complete clinical and radiologic improvement was
      achieved in three months and albendazole treatment lasted six months.

PMID- 30116134
TI  - Benign transient hyperphosphatasemia in an infant during zinc supplementation.
AB  - Benign transient hyperphosphatasemia is characterized by a significant increase
      in alkaline phosphatase levels, which is detected incidentally in infancy and
      children without underlying bone and liver disease. This condition is a
      biochemical disorder rather than a clinical disorder and resolves within a short
      duration. Recognition of this entity by pediatricians is important to avoid
      unnecessary investigations. Here, we report an infant who was diagnosed as having
      benign transient hyperphosphatasemia based on clinical and laboratory findings
      who had increased alkaline phosphatase levels during zinc supplementation, with
      the aim of highlighting benign transient hyperphosphatasemia in infancy and
      childhood.

PMID- 30116136
TI  - Current treatment options for severe autoimmune hemolytic anemia.

PMID- 30116135
TI  - A rare cause of sudden cardiac arrest: Catecholaminergic polymorphic ventricular
      tachycardia.
AB  - Catecholaminergic polymorphic ventricular tachycardia is a rhythm disorder that
      develops due to genetic reasons in the absence of structural cardiac
      abnormalities. Ventricular tachycardia, ventricular fibrillation, cardiac arrest,
      and death may occur. Two-year-old patient presented to the Emergency Department
      with sudden cardiac arrest. He had syncope attacks after playing with his brother
      and he was followed up by the pediatric neurology and cardiology clinics.
      Cardiopulmonary resuscitation was performed, and he was then transferred to the
      Intensive Care Unit because of hypotension; dobutamine and norepinephrine
      treatment was started. After treatment, ventricular tachycardia, ventricular
      fibrillation, and cardiac arrest developed. Dobutamine and noradrenaline was
      stopped immediately and amiodarone was started. A genetic test revealed
      heterozygote missense mutation (c.9110G>A(p.Gly3037Asp)) in exon 64 of the RYR2
      gene, which is compatible with catecholaminergic polymorphic ventricular
      tachycardia. This mutation has been reported in the literature for the first
      time. This case is presented with the purpose of highlighting catecholaminergic
      polymorphic ventricular tachycardia.

PMID- 30116137
TI  - Re: Current treatment options for severe autoimmune hemolytic anemia.

PMID- 30116138
TI  - Reclassification of Parapterulicium Corner (Pterulaceae, Agaricales),
      contributions to Lachnocladiaceae and Peniophoraceae (Russulales) and
      introduction of Baltazaria gen. nov.
AB  - The genus Parapterulicium was first introduced to accommodate two Brazilian
      species of coralloid fungi with affinities to Pterulaceae (Agaricales). Despite
      the coralloid habit and the presence of skeletal hyphae, other features, notably
      the presence of gloeocystidia, dichophyses and papillate hyphal ends,
      differentiate this genus from Pterulaceaesensu stricto. Fieldwork in Brazil
      resulted in the rediscovery of two coralloid fungi identifiable as
      Parapterulicium, the first verified collections of this genus since Corner's
      original work in the 1950s. Molecular phylogenetic analyses of nrITS and nrLSU
      sequences from these modern specimens revealed affinities with the /peniophorales
      clade in the Russulales, rather than Pterulaceae. The presence of distinctive
      hyphal elements, homologous to the defining features of /peniophorales, is
      consistent with the phylogenetic evidence and thus clearly distinguished
      Parapterulicium and its type species P.subarbusculum from Pterulaceae, placing
      this genus within /peniophorales. Parapterulicium was also found to be
      polyphyletic so Baltazaria gen. nov. is proposed to accommodate P.octopodites,
      Scytinostromagalactinum, S.neogalactinum and S.eurasiaticogalactinum also within
      /peniophorales.

PMID- 30116140
TI  - Three new species of Aleurodiscus s.l. (Russulales, Basidiomycota) from southern
      China.
AB  - Three new species of Aleurodiscus s.l. with corticioid basidiomata are described
      and illustrated from southern China based on morphological evidence and
      phylogenetic analyses of ITS and nrLSU sequence data. Aleurodiscusbambusinus was
      collected from Jiangxi Province on bamboo and is distinct by having a compact
      texture, simple-septate generative hyphae, abundant acanthophyses, basidia with
      acanthophysoid appendages and smooth basidiospores. Aleurodiscusisabellinus was
      collected from Yunnan Province on both angiosperm wood and bamboo and is distinct
      by having soft basidiomata with yellow to yellowish-brown hymenophore, yellow
      acanthophyses, simple-septate generative hyphae and smooth basidiospores.
      Aleurodiscussubroseus was collected from Guangxi Autonomous Region and Guizhou
      Province on angiosperm wood and is distinct by having pinkish basidiomata when
      fresh, clamped generative hyphae, clavate acanthophyses and echinulate
      basidiospores. In the phylogenetic tree, A.bambusinus and A.isabellinus were
      nested within the A.cerussatus group, whilst A.subroseus was clustered with
      A.wakefieldiae. An identification key to 26 species of Aleurodiscus s.l. in China
      is provided.

PMID- 30116139
TI  - Phylogeny and taxonomy of Laetiporus (Basidiomycota, Polyporales) with
      descriptions of two new species from western China.
AB  - Laetiporus is a cosmopolitan genus of brown rot fungi. In this study,
      L.medogensis and L.xinjiangensis are described as new species from western China,
      based on morphological and molecular evidence. L.medogensis has only been found
      on gymnosperms so far and is distinguished by pinkish-buff to clay-buff pileal
      surface and buff-yellow pore surface, azonate to faintly zonate pileus and
      ellipsoid to ovoid basidiospores (5-6.2 * 4.2-5.2 MUm). L.xinjiangensis is found
      on angiosperms and is characterised by pale-buff to clay-pink pileal surface,
      cream to light yellow pore surface, azonate to faintly zonate pileus, large pores
      (2-3 per mm) and small basidiospores (4.5-5 * 3-4.2 MUm). The phylogeny of
      Laetiporus is reconstructed with multi-gene sequences including the internal
      transcribed spacer regions (ITS), the large subunit (nrLSU) and small subunit
      (nrSSU) of the nuclear ribosomal RNA gene, the small subunit of the mitochondrial
      rRNA gene (mtSSU), the translation elongation factor 1-alpha gene (EF-1alpha) and
      the second subunit of RNA polymerase II (RPB2). The results show that
      L.medogensis and L.xinjiangensis formed two distinct lineages belonging to
      Laetiporus. Illustrated descriptions of the two new species are presented. An
      identification key to species of L.sulphureus complex is provided.

PMID- 30116141
TI  - Biosafety and biosecurity capacity building: insights from implementation of the
      NUITM-KEMRI biosafety training model.
AB  - The NUITM-KEMRI biosafety training program was developed for capacity building of
      new biosafety level three (BSL-3) laboratory users. The training program
      comprehensively covers biosafety and biosecurity theory and practice. Its
      training curriculum is based on the WHO biosafety guidelines, local biosafety
      standards, and ongoing biosafety level three research activities in the facility,
      also taking into consideration the emerging public health issues. The program's
      training approach enhances the participant's biosafety and biosecurity knowledge
      and builds their skills through the hands-on practice sessions and mentorship
      training. Subsequently, the trainees are able to integrate acquired knowledge and
      good practices into their routine laboratory procedures. This article describes
      implementation of the NUITM-KEMRI biosafety training program.

PMID- 30116142
TI  - Folic Acid Improves the Inflammatory Response in LPS-Activated THP-1 Macrophages.
AB  - DNA methylation has been suggested as a regulatory mechanism behind some
      inflammatory processes. The physiological actions of methyl donors, such as folic
      acid, choline, and vitamin B12 on inflammation-related disease have been
      associated with the synthesis of the universal methyl donor S-adenosyl methionine
      (SAM). The aim of this study was to evaluate the effects of folic acid, choline,
      vitamin B12, and a combination of all on preventing the lipopolysaccharide- (LPS
      ) induced inflammatory response in human THP-1 monocyte/macrophage cells. Folic
      acid and the mixture of methyl donors reduced interleukin 1 beta (IL1B) and
      tumour necrosis factor (TNF) expression as well as protein secretion by these
      cells. Folic acid and choline decreased C-C motif chemokine ligand 2 (CCL2) mRNA
      levels. In addition to this, the methyl donor mixture reduced Cluster of
      differentiation 40 (CD40) expression, but increased serpin family E member 1
      (SERPINE1) expression. All methyl donors increased methylation levels in CpGs
      located in IL1B, SERPINE1, and interleukin 18 (IL18) genes. However, TNF
      methylation was not modified. After treatment with folic acid and the methyl
      donor mixture, ChIP analysis showed no change in the binding affinity of nuclear
      factor-kappaB (NF-kappaB) to IL1B and TNF promoter regions after the treatment
      with folic acid and the methyl donor mixture. The findings of this study suggest
      that folic acid might contribute to the control of chronic inflammation in
      inflammatory-related disease.

PMID- 30116143
TI  - Endothelial Microvesicles and Soluble Markers of Endothelial Injury in Critically
      Ill Newborns.
AB  - Neonatal systemic inflammatory response and multiple organ dysfunction syndrome
      are the main postnatal insults influencing mortality and morbidity. Critically
      ill newborns with high predicted mortality are supported by extracorporeal
      membrane oxygenation (ECMO). Biomarkers of inflammatory response and endothelial
      injury can be used for early diagnosis and treatment of critical neonatal
      situations. The aim of our study was to explore plasma proteins and endothelial
      microvesicles as markers of inflammation and endothelial activation in newborns
      on ECMO and to compare them with healthy neonates. Thirteen newborns on ECMO and
      13 healthy newborns were included in the study. Plasma soluble biomarkers were
      measured using multiplex immunoassay based on Luminex(r) xMAP multianalyte
      profiling platform. The total microvesicle count and plasma level of surface
      antigen-specific microvesicles were determined by flow cytometry. The plasma
      concentration of cell-derived microvesicles was measured using annexin-V
      labeling, and the endothelial origin of microvesicles was determined using
      lineage-specific antigen labeling of endothelial cell/microvesicle markers
      (endoglin/CD105, PECAM1/CD31, VEGFR2/CD309, and MadCAM1). Inflammatory markers
      (procalcitonin, IL-1beta, IL-6, and IL-22) were increased in the ECMO group (P <
      0.01). The assessment of endothelial markers showed higher concentrations of
      endocan and angiopoietin-2 (P < 0.01) in the ECMO group while VEGF in the ECMO
      group was significantly lower (P < 0.01). In the ECMO group, the concentration of
      annexin-V-positive microvesicles (total microvesicles) and endothelial
      microvesicles expressing mucosal vascular addressin cell adhesion molecule 1
      (MadCAM1) was increased (P = 0.05). In summary, we found increased concentrations
      of soluble inflammatory and endothelial markers in the plasma of critically ill
      newborns with multiple organ dysfunction. Increased plasma concentrations of
      microvesicles may reflect the activation or damage of blood cells and vasculature
      including endothelial cells. The measurement of cell membrane-derived
      microvesicles may be added to the panel of established inflammatory markers in
      order to increase the sensitivity and specificity of the diagnostic process in
      critically ill newborns.

PMID- 30116145
TI  - Comment on "Gut Microbiota as a Driver of Inflammation in Nonalcoholic Fatty
      Liver Disease".

PMID- 30116144
TI  - Bioactive Sphingolipids, Complement Cascade, and Free Hemoglobin Levels in Stable
      Coronary Artery Disease and Acute Myocardial Infarction.
AB  - Background: Acute myocardial infarction (AMI) and coronary artery bypass graft
      (CABG) surgery are associated with a pathogen-free inflammatory response (sterile
      inflammation). Complement cascade (CC) and bioactive sphingolipids (BS) are
      postulated to be involved in this process. Aim: The aim of this study was to
      evaluate plasma levels of CC cleavage fragments (C3a, C5a, and C5b9), sphingosine
      (SP), sphingosine-1-phosphate (S1P), and free hemoglobin (fHb) in AMI patients
      treated with primary percutaneous coronary intervention (pPCI) and stable
      coronary artery disease (SCAD) undergoing CABG. Patients and Methods: The study
      enrolled 37 subjects (27 male) including 22 AMI patients, 7 CABG patients, and 8
      healthy individuals as the control group (CTRL). In the AMI group, blood samples
      were collected at 5 time points (admission to hospital, 6, 12, 24, and 48 hours
      post pPCI) and 4 time points in the CABG group (6, 12, 24, and 48 hours post
      operation). SP and S1P concentrations were measured by high-performance liquid
      chromatography (HPLC). Analysis of C3a, C5a, and C5b9 levels was carried out
      using high-sensitivity ELISA and free hemoglobin by spectrophotometry. Results:
      The plasma levels of CC cleavage fragments (C3a and C5b9) were significantly
      higher, while those of SP and S1P were lower in patients undergoing CABG surgery
      in comparison to the AMI group. In both groups, levels of CC factors showed no
      significant changes within 48 hours of follow-up. Conversely, SP and S1P levels
      gradually decreased throughout 48 hours in the AMI group but remained stable
      after CABG. Moreover, the fHb concentration was significantly higher after 24 and
      48 hours post pPCI compared to the corresponding postoperative time points.
      Additionally, the fHb concentrations increased between 12 and 48 hours after PCI
      in patients with AMI. Conclusions: Inflammatory response after AMI and CABG
      differed regarding the release of sphingolipids, free hemoglobin, and complement
      cascade cleavage fragments.

PMID- 30116146
TI  - Neutrophil-to-Lymphocyte Ratio, Monocyte-to-Lymphocyte Ratio, Platelet-to
      Lymphocyte Ratio, and Mean Platelet Volume-to-Platelet Count Ratio as Biomarkers
      in Critically Ill and Injured Patients: Which Ratio to Choose to Predict Outcome
      and Nature of Bacteremia?
AB  - Background: Neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio
      (MLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume-to-platelet
      count (MPV/PC) ratio are readily available parameters that might have
      discriminative power regarding outcome. The aim of our study was to assess
      prognostic value of these biomarkers regarding outcome in critically ill patients
      with secondary sepsis and/or trauma. Methods: A total of 392 critically ill and
      injured patients, admitted to surgical ICU, were enrolled in a prospective
      observational study. Leukocyte and platelet counts were recorded upon fulfilling
      Sepsis-3 criteria and for traumatized Injury Severity Score > 25 points. Patients
      were divided into four subgroups: peritonitis, pancreatitis, trauma with sepsis,
      and trauma without sepsis. Results: NLR and MPV/PC levels were significantly
      higher in nonsurvivors (AUC/ROC of 0.681 and 0.592, resp., in the peritonitis
      subgroup; 0.717 and 0.753, resp., in the pancreatitis subgroup); MLR and PLR did
      not differ significantly. There was no significant difference of investigated
      biomarkers between survivors and nonsurvivors in trauma patients with and without
      sepsis except for PLR in the trauma without sepsis subgroup (significantly higher
      in nonsurvivors, AUC/ROC of 0.719). Independent predictor of lethal outcome was
      NLR in the whole cohort and in the peritonitis subgroup as well as MPV in the
      pancreatitis subgroup. Also, there were statistically significant differences in
      MPV/PC, MLR, and PLR values regarding nature of bacteremia. In general, the
      lowest levels had been found in patients with Gram-positive blood cultures.
      Conclusions: NLR and MPV were very good independent predictors of lethal outcome.
      For the first time, we demonstrate that nature of bacteremia influences MPV/PC,
      MLR, and PLR. In heterogeneous cohort subgroup, analysis is essential.

PMID- 30116147
TI  - Epac1 Restores Normal Insulin Signaling through a Reduction in Inflammatory
      Cytokines.
AB  - We have previously reported that Epac1 reduced inflammatory cytokines, which is
      protective to the diabetic retina. We have also published that impaired insulin
      signaling occurs in the diabetic retina. A reduction in interleukin-1 beta (IL
      1beta) and tumor necrosis factor alpha (TNFalpha) by Epac1 could potentially
      restore normal insulin signal transduction. Confocal microscopy was performed to
      localize the insulin receptor in the retina of Epac1 floxed and endothelial cell
      specific Epac1 knockout mice. Whole retinal lysates from Epac1 floxed and
      endothelial cell-specific Epac1 knockout mice were used to investigate proteins
      involved in the insulin signaling cascade. Primary human REC were cultured in
      normal and high glucose followed by Epac1 agonist treatment or transfection with
      IL-1beta or TNFalpha siRNA for protein analyses of insulin signaling proteins.
      Decreased expression of the insulin receptor was observed in the Epac1 knockout
      mouse retinal vasculature compared to floxed littermates. Work in mice showed
      that loss of Epac1 decreased insulin signaling proteins. Treatment with an Epac1
      agonist decreased p38 and JNK signaling and increased insulin signaling, as did
      inhibition of IL-1beta or TNFalpha using siRNA when added to REC grown in high
      glucose. Taken together, Epac1 can restore normal insulin signaling in the
      retinal vasculature through reductions in inflammatory cytokines.

PMID- 30116148
TI  - Oxidative and Antioxidative Stress Status in Children with Inflammatory Bowel
      Disease as a Result of a Chronic Inflammatory Process.
AB  - Oxidative stress (OS) has been recently implicated in the disease pathogenesis in
      inflammatory bowel disease (IBD). The aim of the study was to evaluate oxidative
      and antioxidative stress status and the risk of the atherosclerotic process in
      children with IBD and functional gastrointestinal disorders (FGID). The
      prospective study included a group of 71 children during a period of 2 years. In
      all children, laboratory tests were performed and intima-media complex in the
      carotid artery was measured (IMC). Low values of OS were more frequent in
      children with IBD than in the FGID group. The average concentration of oxidized
      lipoprotein with average density (oxLDL) was lower in patients with IBD. Among
      patients with IBD, higher concentrations of oxLDL were recorded in patients with
      longer-duration disease and with higher concentrations of total cholesterol. In
      the IBD group, more often, higher concentrations of anti-oxLDL were recorded
      among patients with longer-duration disease. The obtained results did not support
      the hypothesis of total antioxidant capacity depletion and greater overall OS in
      patients with IBD. Patients with IBD with a longer duration of the disease have
      higher concentrations of oxLDL and anti-oxLDL.

PMID- 30116149
TI  - Mobilized Peripheral Blood versus Cord Blood: Insight into the Distinct Role of
      Proinflammatory Cytokines on Survival, Clonogenic Ability, and Migration of CD34+
      Cells.
AB  - Inflammation may play a role in cancer. However, the contribution of cytokine
      mediated crosstalk between normal hemopoietic stem/progenitor cells (HSPCs) and
      their (inflammatory) microenvironment is largely elusive. Here we compared
      survival, phenotype, and function of neonatal (umbilical cord blood (CB)) and
      adult (normal G-CSF-mobilized peripheral blood (mPB)) CD34+ cells after in vitro
      exposure to combined crucial inflammatory factors such as interleukin- (IL-)
      1beta, IL-6, tumor necrosis factor- (TNF-) alpha, or tissue inhibitor of
      metalloproteinases-1 (TIMP-1). To mimic bone marrow (BM) niche, coculture
      experiments with normal BM stromal cells (BMSCs) were also performed. We found
      that combined inflammatory cytokines increased only the in vitro survival of CB
      derived CD34+ cells by reducing apoptosis. Conversely, selected combinations of
      inflammatory cytokines (IL-1beta + TNF-alpha, IL-6 + TNF-alpha, and IL-1beta +
      TNF-alpha + TIMP-1) mainly enhanced the in vitro CXCR4-driven migration of mPB
      derived CD34+ cells. TNF-alpha, alone or in combination, upregulated CD44 and
      CD13 expression in both sources. Finally, BMSCs alone increased
      survival/migration of CB- and mPB-derived CD34+ cells at the same extent of the
      combined inflammatory cytokines; importantly, their copresence did not show
      additive/synergistic effect. Taken together, these data indicate that combined
      proinflammatory stimuli promote distinct in vitro functional activation of
      neonatal or adult normal HSPCs.

PMID- 30116151
TI  - Erratum to "Mold Alkaloid Cytochalasin D Modifies the Morphology and Secretion of
      fMLP-, LPS-, or PMA-Stimulated Neutrophils upon Adhesion to Fibronectin".
AB  - [This corrects the article DOI: 10.1155/2017/4308684.].

PMID- 30116150
TI  - Knockdown of Sestrin2 Increases Lipopolysaccharide-Induced Oxidative Stress,
      Apoptosis, and Fibrotic Reactions in H9c2 Cells and Heart Tissues of Mice via an
      AMPK-Dependent Mechanism.
AB  - Sestrin2 (sesn2) is an endogenous antioxidant protein that has recently gained
      attention for its potential to treat various inflammatory diseases. However, the
      relationship of sesn2 with cardiomyopathy is still unclear. In H9c2 cells, sesn2
      knockdown reduced the level of 5' adenosine monophosphate-activated protein
      kinase (AMPK) phosphorylation, downregulated antioxidant genes including catalase
      and superoxide dismutase (SOD2), and increased reactive oxygen species (ROS)
      production upon lipopolysaccharide (LPS) treatment. LPS-mediated cell death and
      the expression of matrix metalloproteinase (MMP) 2 and MMP9 were significantly
      increased by sesn2 knockdown. However, these increases were prevented by
      treatment with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an AMPK
      activator. Consistent with the in vitro results, AMPK phosphorylation was
      decreased in heart tissue from sesn2 knockdown mice compared to heart tissue from
      control C57BL/6 mice, which was associated with decreased expression of
      antioxidant genes and increased LPS-mediated cell death signaling. Furthermore,
      the decrease in AMPK phosphorylation caused by sesn2 knockdown increased LPS
      mediated expression of cardiac fibrotic factors, including collagen type I and
      type III, in addition to MMP2 and MMP9, in heart tissue from C57BL/6 mice. These
      results suggest that sesn2 is a novel potential therapeutic target for
      cardiomyopathy under inflammatory conditions.

PMID- 30116152
TI  - Polymorphonuclear Leukocytes or Hydrogen Peroxide Enhance Biofilm Development of
      Mucoid Pseudomonas aeruginosa.
AB  - Pseudomonas aeruginosa is an opportunistic pathogenic bacterium involved in many
      human infections, including pneumonia, diabetic foot ulcers, and ventilator
      associated pneumonia. P. aeruginosa cells usually undergo mucoid conversion
      during chronic lung infection in patients with cystic fibrosis (CF) and resist
      destruction by polymorphonuclear leukocytes (PMNs), which release free oxygen
      radicals (ROS), such as H2O2. PMNs are the main leucocytes in the CF sputum of
      patients who are infected with P. aeruginosa, which usually forms biofilms. Here,
      we report that PMNs or H2O2 can promote biofilm formation by mucoid P. aeruginosa
      FRD1 with the use of the hanging-peg method. The mucoid strain infecting CF
      patients overproduces alginate. In this study, PMNs and H2O2 promoted alginate
      production, and biofilms treated with PMNs or H2O2 exhibited higher expression of
      alginate genes. Additionally, PMNs increased the activity of GDP-mannose
      dehydrogenase, which is the key enzyme in alginate biosynthesis. Our results
      demonstrate that PMNs or H2O2 can enhance mucoid P. aeruginosa biofilms.

PMID- 30116153
TI  - Involvement of the IL23/Th17 Pathway in the Pathogenesis of Tunisian Pemphigus
      Foliaceus.
AB  - Pemphigus foliaceus (PF) is a rare autoimmune skin disease caused by anti-Dsg1
      pathogenic autoantibodies. It is considered as a Th2-mediated disease. Likewise,
      Th17 cells were recently described in the pathogenesis of the disease but their
      role is still unclear. We aimed to unravel the eventual implication of the
      IL23/Th17 pathway in the development of PF. A case-control study was conducted on
      115 PF patients and 201 healthy controls using PCR-RFLP and AS-PCR methods. SNPs
      in IL23R, RORgammat, IL17A, IL17F, IL17AR, TNFa, and STAT3 genes were genotyped.
      mRNA expression of IL23R and RORgammat was evaluated using Q-PCR. The frequency
      of circulating Th17 cells was analyzed by flow cytometry. Genetic associations
      between IL23R>rs11209026, IL17A>rs3748067, IL17F>rs763780, and TNFa>rs1800629 and
      the susceptibility to PF were reported. Moreover, we revealed a significant
      increased frequency of circulating CD4+IL17+ cells as well as higher mRNA levels
      of RORgammat and IL23R in PBMCs of patients. However, no significant increase of
      RORgammat and IL23R mRNA expression was observed in lesional skin biopsies. In
      spite of the little size of specimens, our results provide converging arguments
      for the contribution of the IL23/Th17 pathway in the pathogenesis of PF.

PMID- 30116156
TI  - Immune Response in Critically Ill Patients.

PMID- 30116155
TI  - Intrauterine Malnutrition Reduced Long Leptin Receptor Isoform Expression and
      Proinflammatory Cytokine Production in Male Rat Pulmonary Endothelial Cells
      Stimulated by Lipopolysaccharide.
AB  - Background/Aims: We have previously shown that low birth weight (LBW) rats
      exposed to intrauterine malnutrition have an impaired lung inflammatory response
      and reduced levels of inflammatory mediators; however, circulating leptin levels
      were not increased. We evaluated long leptin receptor isoform (ObRb) expression
      in lung endothelial cells from low birth weight rats and examined its role in the
      production of lipid mediators and cytokines. Methods: Lung endothelial cells were
      obtained from normal birth weight (NBW) rats or LBW rats subjected to
      intrauterine malnutrition. These cells were stimulated with leptin (10 ng/mL),
      LPS (lipopolysaccharide, 1 MUg/mL), or leptin plus LPS. Six hours after
      stimulation, the production of inflammatory mediators (PGE2, LTB4, IL-1beta, and
      IL-6) was evaluated using commercial ELISA kits, and Western blotting was
      performed to investigate p38MAPK, NF-kappaB, and ObRb expression. Results: Leptin
      increased IL-1beta levels in only cells from the NBW group, whereas LPS increased
      PGE2 and LTB4 levels in cells from both groups; leptin addition potentiated lipid
      mediator production induced by LPS in the NBW group. LPS enhanced the production
      of IL-1beta and IL-6 in only endothelial cells from NBW rats. Leptin receptor
      expression was decreased (63%) in endothelial cells from LBW rats. None of the
      stimuli increased NF-kappaB or p38 signaling pathway expression in cells from LBW
      rats. Conclusion: These results suggest that intrauterine malnutrition
      compromises leptin receptor expression and cytokine production in pulmonary
      endothelial cells stimulated by LPS; these effects seem to involve the NF-kappaB
      and p38MAPK signaling pathways.

PMID- 30116157
TI  - Allergic rhinitis and periodontitis among Korean adults: results from a
      nationwide population-based study (2013-2015).
AB  - Background: The purpose of this study was to examine whether allergic rhinitis is
      associated with periodontal disease in a representative sample of elderly Korean
      people that was adjusted for socio-demographic factors, oral and general health
      behaviors, and systemic health status. Methods: A total of 10,643 subjects who
      were between 20 and 59 years of age participated in the Korean National Health
      and Nutrition Examination Survey and underwent cross-sectional examination.
      Medical history of allergic rhinitis was collected from participants by
      questionnaire; additionally, periodontal status was assessed using a Community
      Periodontal Index score of 3 or 4. Multivariate logistic regression analysis was
      conducted to adjust for socio-demographic variables, oral health status and
      behaviors, and general health status and behaviors. All analyses were performed
      using a complex sampling design. Results: Allergic rhinitis and periodontitis
      showed a significant inverse association. After adjusting for all confounders, a
      trend of decreasing periodontitis risk was observed as allergic rhinitis
      increased. The adjusted odds ratio of periodontitis was 0.79 (0.66-0.95) for
      patients with allergic rhinitis. Conclusion: A significant inverse association
      between allergic rhinitis and periodontal status was demonstrated in this patient
      population.

PMID- 30116158
TI  - Survival in sinonasal and middle ear malignancies: a population-based study using
      the SEER 1973-2015 database.
AB  - Background: The sinuses, nasal cavity, and middle ear represent a rarer location
      of head and neck malignancy than more common sites such as the larynx and oral
      cavity. Population-based studies are a useful tool to study the demographic and
      treatment factors affecting survival in these malignancies. Methods: Population
      based database search of the Survival, Epidemiology, and End Results (SEER)
      database from 1973 to 2015 for malignancies involving the nasal cavity, paranasal
      sinuses, and middle ear. Data were analyzed for demographics, treatment type,
      stage, primary site and histopathologic type. Kaplan-Meier analysis was used to
      assess and compare survival. Results: A total of 13,992 cases of sinonasal or
      middle ear malignancy were identified and analyzed. The majority of patients were
      between ages 50 and 80 at the time of diagnosis. Overall 5-, 10-, and 20-year
      survival was 45.7%, 32.2%, and 16.4%, respectively. Lymph node metastasis was
      reported in 4.4% of patients, while distant metastasis was present in 1.5% of
      cases. On univariate analysis surgical vs. nonsurgical treatment, sex, race, age
      at diagnosis, T stage, N stage, M stage, AJCC overall stage, primary site, tumor
      grade, and histopathologic subtype significantly affected survival. On
      multivariate analysis age, race, sex, primary site, overall AJCC stage, surgical
      vs. nonsurgical treatment, and T, N, and M stage remained significant predictors
      of overall survival. Conclusions: Malignancies of the nasal cavity, paranasal
      sinuses, and middle ear account for a minority of overall head and neck cancers.
      The overall 5-, 10-, and 20-year survival for these malignancies is relatively
      low. Higher T, N, M, and overall stage and higher tumor grade is associated with
      lower survival. Patients treated with surgery as part of the treatment regimen
      had higher overall survival. Demographics and primary site also significantly
      affect survival. Certain histopathologic subtypes were associated with poorer
      survival.

PMID- 30116159
TI  - "That's not me anymore": Resistance strategies for managing intersectional
      stigmas for women with substance use and incarceration histories.
AB  - Significant previous research has focused on how individuals experience stigma
      when interacting with the public sphere and service agencies; the purpose of this
      grounded theory study is to explore how formerly incarcerated mothers with
      histories of substance use experience stigmas from their intimate relationships
      with family and romantic partners. Using an intersectionality lens, this study
      reveals that the women perceived multiple stigmas due to their previous substance
      use, incarceration, and other addiction-related behaviors that challenged their
      roles as mothers and romantic partners. Compounding the behavioral-related
      stigmas were race and class-based stereotypes of black criminality that also
      challenged women's ability to embody key motherhood and womanhood roles. As a
      result, the women employed resistance strategies to safeguard against stigma and
      preserve their recovery. The implications for practice underscore the
      significance of addressing personal experiences of stigma, complex relational
      dynamics, and understanding the needs of support systems that are also shaped by
      the women's cycles of incarceration and illness.

PMID- 30116154
TI  - Regulation of Metabolic Disease-Associated Inflammation by Nutrient Sensors.
AB  - Visceral obesity is frequently associated with the development of type 2 diabetes
      (T2D), a highly prevalent chronic disease that features insulin resistance and
      pancreatic beta-cell dysfunction as important hallmarks. Recent evidence
      indicates that the chronic, low-grade inflammation commonly associated with
      visceral obesity plays a major role connecting the excessive visceral fat
      deposition with the development of insulin resistance and pancreatic beta-cell
      dysfunction. Herein, we review the mechanisms by which nutrients modulate obesity
      associated inflammation.

PMID- 30116160
TI  - Magnetosomes Extracted from Magnetospirillum gryphiswaldense as Theranostic
      Agents in an Experimental Model of Glioblastoma.
AB  - Magnetic fluid hyperthermia (MFH) with chemically synthesized nanoparticles is
      currently used in clinical trials as it destroys tumor cells with an extremely
      localized deposition of thermal energy. In this paper, we investigated an MFH
      protocol based on magnetic nanoparticles naturally produced by magnetotactic
      bacteria: magnetosomes. The efficacy of such protocol is tested in a xenograft
      model of glioblastoma. Mice receive a single intratumoral injection of
      magnetosomes, and they are exposed three times in a week to an alternating
      magnetic field with concurrent temperature measurements. MRI is used to visualize
      the nanoparticles and to monitor tumor size before and after the treatment.
      Statistically significant inhibition of the tumor growth is detected in subjects
      exposed to the alternating magnetic field compared to control groups. Moreover,
      thanks to magnetosomes high transversal relaxivity, their effective delivery to
      the tumor tissue is monitored by MRI. It is apparent that the efficacy of this
      protocol is limited by inhomogeneous delivery of magnetosomes to tumor tissue.
      These results suggest that naturally synthesized magnetosomes could be
      effectively considered as theranostic agent candidates for hyperthermia based on
      iron oxide nanoparticles.

PMID- 30116162
TI  - Isolated Perfused Rat Livers to Quantify the Pharmacokinetics and Concentrations
      of Gd-BOPTA.
AB  - With recent advances in liver imaging, the estimation of liver concentrations is
      now possible following the injection of hepatobiliary contrast agents and
      radiotracers. However, how these images are generated remains partially unknown.
      Most experiments that would be helpful to increase this understanding cannot be
      performed in vivo. For these reasons, we investigated the liver distribution of
      the magnetic resonance (MR) contrast agent gadobenate dimeglumine (Gd-BOPTA,
      MultiHance(r), Bracco Imaging) in isolated perfused rat livers (IPRLs). In IPRL,
      we developed a new set up that quantifies simultaneously the Gd-BOPTA compartment
      concentrations and the transfer rates between these compartments. Concentrations
      were measured either by MR signal intensity or by count rates when the contrast
      agent was labelled by [153Gd]. With this experimental model, we show how the Gd
      BOPTA hepatocyte concentrations are modified by temperature and liver flow rates.
      We define new pharmacokinetic parameters to quantify the canalicular transport of
      Gd-BOPTA. Finally, we present how transfer rates generate Gd-BOPTA concentrations
      in rat liver compartments. These findings better explain how liver imaging with
      hepatobiliary radiotracers and contrast agents is generated and improve the image
      interpretation by clinicians.

PMID- 30116161
TI  - A New High-Performance Gadonanotube-Polymer Hybrid Material for Stem Cell
      Labeling and Tracking by MRI.
AB  - A gentle, rapid method has been developed to introduce a polyacrylic acid (PAA)
      polymer coating on the surface of gadonanotubes (GNTs) which significantly
      increases their dispersibility in water without the need of a surfactant. As a
      result, the polymer, with its many carboxylic acid groups, coats the surface of
      the GNTs to form a new GNT-polymer hybrid material (PAA-GNT) which can be highly
      dispersed in water (ca. 20 mg.mL-1) at physiological pH. When dispersed in water,
      the new PAA-GNT material is a powerful MRI contrast agent with an extremely short
      water proton spin-lattice relaxation time (T1) which results in a T1-weighted
      relaxivity of 150 mM-1.s-1 per Gd3+ ion at 1.5 T. Furthermore, the PAA-GNTs have
      been used to safely label porcine bone-marrow-derived mesenchymal stem cells for
      magnetic resonance imaging. The labeled cells display excellent image contrast in
      phantom imaging experiments, and transmission electron microscopy images of the
      labeled cells reveal the presence of highly dispersed PAA-GNTs within the
      cytoplasm with 1014 Gd3+ ions per cell.

PMID- 30116163
TI  - Assessment of the Aging of the Brown Adipose Tissue by 18F-FDG PET/CT Imaging in
      the Progeria Mouse Model Lmna-/.
AB  - Brown adipose tissue (BAT) is an important energy metabolic organ that is highly
      implicated in obesity, type 2 diabetes, and atherosclerosis. Aging is one of the
      most important determinants of BAT activity. In this study, we used 18F-FDG
      PET/CT imaging to assess BAT aging in Lmna-/- mice. The maximum standardized
      uptake value (SUVMax) of the BAT was measured, and the target/nontarget (T/NT)
      values of BAT were calculated. The transcription and the protein expression
      levels of the uncoupling protein 1 (UCP1), beta3-adrenergic receptor (beta3-AR),
      and the PR domain-containing 16 (PRDM16) were measured by quantitative real-time
      polymerase chain reaction (RT-PCR) and Western blotting or immunohistochemical
      analysis. Apoptosis and cell senescence rates in the BAT of WT and Lmna-/- mice
      were determined by terminal deoxynucleotidyl transferase dUTP nick end labeling
      (TUNEL) and by CDKN2A/p16INK4a immunohistochemical staining, respectively. At 14
      weeks of age, the BAT SUVMax and the expression levels of UCP1, beta3-AR, and
      PRDM16 in Lmna-/- mice were significantly reduced relative to WT mice. At the
      same time, the number of p16INK4a and TUNEL positively stained cells (%)
      increased in Lmna-/- mice. Collectively, our results indicate that the aging
      characteristics and the aging regulatory mechanism in the BAT of Lmna-/- mice can
      mimic the normal BAT aging process.

PMID- 30116164
TI  - Noninvasive Monitoring of Liver Disease Regression after Hepatitis C Eradication
      Using Gadoxetic Acid-Enhanced MRI.
AB  - We evaluated changes in relative liver enhancement (RLE) obtained by gadoxetic
      acid-enhanced MRI (GA-MRI) in the hepatobiliary phase and changes in splenic
      volume (SV) after hepatitis C virus (HCV) eradication as well as their predictive
      value for the development of (further) hepatic decompensation during follow-up.
      This retrospective study comprised 31 consecutive patients with HCV-induced
      advanced chronic liver disease who underwent GA-MRI before and after successful
      interferon-free treatment, as well as a cohort of 14 untreated chronic HCV
      patients with paired GA-MRI. RLE increased by 66% (20%-94%; P < 0.001) from pre-
      to posttreatment, while SV decreased by -16% (-28% to -8%; P < 0.001). However,
      SV increased in 16% (5/31) of patients, the identical subjects who showed a
      decrease in RLE (GA-MRI-nonresponse). We observed an inverse correlation between
      the changes in RLE and SV (rho=-0.608; P < 0.001). In the untreated patients,
      there was a decrease in RLE by -11% (-25% to -3%; P=0.019) and an increase in SV
      by 23% (7%-43%; P=0.004) (both P < 0.001 versus treated patients). Interestingly,
      GA-MRI-nonresponse was associated with a substantially increased risk of
      (further) hepatic decompensation 2 years after the end of treatment: 80% versus
      8%; P < 0.001. GA-MRI might distinguish between individuals at low and high risk
      of (further) hepatic decompensation (GA-MRI-nonresponse) after HCV eradication.
      This could allow for individualized surveillance strategies.

PMID- 30116165
TI  - Early Imaging Biomarker of Myocardial Glucose Adaptations in High-Fat-Diet
      Induced Insulin Resistance Model by Using 18F-FDG PET and [U-13C]glucose Nuclear
      Magnetic Resonance Tracer.
AB  - Background: High-fat diet (HFD) induces systemic insulin resistance leading to
      myocardial dysfunction. We aim to characterize the early adaptations of
      myocardial glucose utility to HFD-induced insulin resistance. Methods: Male
      Sprague-Dawley rats were assigned into two groups, fed a regular chow diet or HFD
      ad libitum for 10 weeks. We used in vivo imaging of cardiac magnetic resonance
      (CMR), 18F-FDG PET, and ex vivo nuclear magnetic resonance (NMR) metabolomic
      analysis for the carbon-13-labeled glucose ([U-13C]Glc) perfused myocardium.
      Results: As compared with controls, HFD rats had a higher ejection fraction and a
      smaller left ventricular end-systolic volume (P < 0.05), with SUVmax of
      myocardium on 18F-FDG PET significantly increased in 4 weeks (P < 0.005). The [U
      13C]Glc probed the increased glucose uptake being metabolized into pyruvate and
      acetyl-CoA, undergoing oxidative phosphorylation via the tricarboxylic acid (TCA)
      cycle, and then synthesized into glutamic acid and glutamine, associated with
      overexpressed LC3B (P < 0.05). Conclusions: HFD-induced IR associated with
      increased glucose utility undergoing oxidative phosphorylation via the TCA cycle
      in the myocardium is supported by overexpression of glucose transporter, acetyl
      CoA synthase. Noninvasive imaging biomarker has potentials in detecting the
      metabolic perturbations prior to the decline of the left ventricular function.

PMID- 30116166
TI  - The EPA Cancer Risk Assessment Default Model Proposal: Moving Away From the LNT.
AB  - This article strongly supports the Environmental Protection Agency proposal to
      make significant changes in their cancer risk assessment principles and practices
      by moving away from the use of the linear nonthreshold (LNT) dose-response as the
      default model. An alternate approach is proposed based on model uncertainty which
      integrates the most scientifically supportable features of the threshold,
      hormesis, and LNT models to identify the doses that optimize population-based
      responses (ie, maximize health benefits/minimize health harm). This novel
      approach for cancer risk assessment represents a significant improvement to the
      current LNT default method from scientific and public health perspectives.

PMID- 30116167
TI  - Role of N-Acetylcysteine and Coenzyme Q10 in the Amelioration of Myocardial
      Energy Expenditure and Oxidative Stress, Induced by Carbon Tetrachloride
      Intoxication in Rats.
AB  - This study is designed to evaluate the potential impact of N-acetyl cysteine
      (NAC) and coenzyme Q10 (CoQ10) each alone or in combination against carbon
      tetrachloride (CCl4)-induced cardiac damage in rats. Animals were treated with
      CCl4 in single intraperitoneal dose of 1 mL/Kg body weight; CCl4-intoxicated
      animals were pretreated with 20 mg/kg/d NAC or pretreated with 200 mg/kg/d CoQ10
      or NAC and CoQ10 with the same previously mentioned doses. Carbon tetrachloride
      intoxicated rats showed a significant elevation in nitric oxide and lipid
      peroxides and downregulation in reduced glutathione level and calcium adenosine
      triphosphatase. Cardiac glycolytic enzymes levels such as lactate dehydrogenase,
      phosphofructokinase, and hexokinase were declined coupled with a reduction in
      glucose content after CCl4 treatment. Moreover, myocardial hydroxyproline level
      was significantly increased after CCl4-treatment indicating accumulation of
      interstitial collagen. N-acetyl cysteine and/or CoQ10 effectively alleviated the
      disturbances in myocardial oxidative stress and antioxidant markers. These
      antioxidants effectively upregulated the reduction in cardiac energetic
      biomarkers due to CCl4 treatment. N-acetyl cysteine and/or CoQ10 significantly
      decreased hydroxyproline level compared to that of CCl4-treated rats. The current
      data showed that the aforementioned antioxidants have a remarkable
      cardioprotective effect, suggesting that they may be useful as prophylactic
      agents against the detrimental effects of cardiotoxins.

PMID- 30116169
TI  - Cytotoxic Profiling of Endogenous Metabolites Relevant to Chronic Fatigue Immune
      Dysfunction Syndrome (CFIDS) on p53 Variant Human Colon Carcinoma Cell Lines.
AB  - Chemoprophylatic strategies against development of multifactorial diseases
      utilize compounds to block the multistep events in chronic inflammation and
      carcinogenesis. The successful chemopreventative candidate must therefore
      selectively inhibit growth of transformed cells and be administered frequently to
      confer maximal protection with minimal side effects. In addition to synthetic and
      exogenous natural compounds, endogenous metabolites represent another class of
      compounds that exhibit anticarcinogenic and anti-inflammatory properties
      contributing to proper cell function. To assess the effectiveness of these
      compounds warrants an understanding of their cytotoxic mode of action. In this
      study, p53 variant human colon carcinoma cell lines were chronically exposed to
      varying concentrations of the endogenous metabolites-phenyl acetate,
      ursodeoxycholate, and tauroursodeoxycholate-to determine the role of p53-induced
      cytotoxicity, with p53 mutant and deficient cell lines representing precancerous
      lesions. Cytotoxicity was assessed using clonogenic assays, and macroscopic
      colony counts were used to quantify cell survival. The results demonstrate that
      the bile acids, ursodeoxycholate and tauroursodeoxycholate, exhibit selective
      cytotoxicity toward nonfunctional p53 cell lines suggesting a p53-mediated role
      in inhibition of cell clonogenicity and potential chemopreventative properties.
      Although each compound displays this described effect, the tauroursodeoxycholate
      demonstrates high significance suggesting it might have practical uses in vivo.

PMID- 30116168
TI  - Liposomal Curcumin Attenuates the Incidence of Oxidative Stress, Inflammation,
      and DNA Damage Induced by Copper Sulfate in Rat Liver.
AB  - Background: Copper is an essential element that is used widely in agriculture as
      fungicides and insecticides; for example, it is used to control schistosomiasis
      and as an antiseptic and germicide. Copper sulfate (CuSO4) induces multiorgan
      dysfunction through the stimulation of reactive oxygen species and oxidative
      stress. Despite the numerous pharmacological effects of curcumin (CUR), its
      pharmacokinetic properties are less promising. Hence, there is an urgent need for
      novel, effective strategies to attenuate heavy metal toxicity and consequently
      improve the treatment efficiency. Liposomal curcumin (L-CUR) improves the
      dissolution, stability, and bioavailability of treatment agents. This study
      compared the efficacy of CUR and L-CUR with that of desferrioxamine (DES), which
      is a heavy metal chelator against CuSO4 hepatotoxicity. Methods: All treatments
      with the aforementioned antioxidants were administered for 7 days along with
      CuSO4. Serum levels of alanine aminotransferase, aspartate transaminase, lactate
      dehydrogenase, and C-reactive protein, hepatic nitric oxide (NO), and lipid
      peroxides (malondialdehyde) were measured; protein expression of cyclooxygenase 2
      and DNA fragmentation were evaluated. Histopathological examinations were also
      conducted. Results: A toxic dose of CuSO4 induced elevations in the previously
      measured parameters; these increases were reduced by the tested antioxidants,
      whereas glutathione (GSH) and superoxide dismutase (SOD) levels were decreased.
      Treatment with the antioxidants in question modulated these levels. Liposomal CUR
      has more hepatoprotective efficiency than CUR, and its efficacy was similar to
      that of DES. The histopathological examinations confirmed these results.
      Conclusions: Liposomal CUR may be useful for the prevention of CuSO4-induced
      liver injury. Cyclooxygenase 2 protein expression and DNA fragmentation were
      involved in CuSO4 toxicity and treatment.

PMID- 30116171
TI  - Corrigendum.
AB  - [This corrects the article DOI: 10.1177/1559325817748121.].

PMID- 30116170
TI  - A Comet Assay for DNA Damage and Repair After Exposure to Carbon-Ion Beams or X
      rays in Saccharomyces Cerevisiae.
AB  - Ionizing radiation (IR) can result in serious genomic instability and
      genotoxicity by causing DNA damage. Carbon ion (CI) beams and X-rays are typical
      IRs and possess high-linear energy transfer (LET) and low-LET, respectively. In
      this article, a comet assay that was optimized by decreasing the electrophoresis
      time (8 minutes) and voltage (0.5 V/cm) was performed to elucidate and quantify
      the DNA damage induced by CI or X-rays radiation. Two quantitative methods for
      the comet assay, namely, comet score and olive tail moment, were compared, and
      the appropriate means and parameter values were selected for the present assay.
      The dose-effect relationship for CI or X-rays radiation and the DNA repair
      process were studied in yeast cells. These results showed that the quadratic
      function fitted the dose-effect relationship after CI or X-rays exposure, and the
      trend for the models fitted the dose-effect curves for various repair times was
      precisely described by the cubic function. A kinetics model was also creatively
      used to describe the process of DNA repair, and equations were calculated within
      repairable ranges that could be used to roughly evaluate the process and time
      necessary for DNA repair.

PMID- 30116172
TI  - Mechanistic Insights Into MicroRNA-Induced Neuronal Reprogramming of Human Adult
      Fibroblasts.
AB  - The use of transcriptional factors as cell fate regulators are often the primary
      focus in the direct reprogramming of somatic cells into neurons. However, in
      human adult fibroblasts, deriving functionally mature neurons with high
      efficiency requires additional neurogenic factors such as microRNAs (miRNAs) to
      evoke a neuronal state permissive to transcription factors to exert their
      reprogramming activities. As such, increasing evidence suggests brain-enriched
      miRNAs, miR-9/9* and miR-124, as potent neurogenic molecules through
      simultaneously targeting of anti-neurogenic effectors while allowing additional
      transcription factors to generate specific subtypes of human neurons. In this
      review, we will focus on methods that utilize neuronal miRNAs and provide
      mechanistic insights by which neuronal miRNAs, in synergism with brain-region
      specific transcription factors, drive the conversion of human fibroblasts into
      clinically relevant subtypes of neurons. Furthermore, we will provide insights
      into the age signature of directly converted neurons and how the converted human
      neurons can be utilized to model late-onset neurodegenerative disorders.

PMID- 30116174
TI  - Dysregulation of Parvalbumin Expression in the Cntnap2-/- Mouse Model of Autism
      Spectrum Disorder.
AB  - Due to the complex and heterogeneous etiology of autism spectrum disorder (ASD),
      identification of convergent pathways and/or common molecular endpoints in the
      pathophysiological processes of ASD development are highly needed in order to
      facilitate treatment approaches targeted at the core symptoms. We recently
      reported on decreased expression of the Ca2+-binding protein parvalbumin (PV) in
      three well-characterized ASD mouse models, Shank1-/-, Shank3B-/- and in utero VPA
      exposed mice. Moreover, PV-deficient mice (PV+/- and PV-/-) were found to show
      behavioral impairments and neuroanatomical changes closely resembling those
      frequently found in human ASD individuals. Here, we combined a stereology-based
      approach with molecular biology methods to assess changes in the subpopulation of
      PV-expressing (Pvalb) interneurons in the recently characterized contactin
      associated protein-like 2 (Cntnap2-/-) knockout mouse model of ASD. The CNTNAP2
      gene codes for a synaptic cell adhesion molecule involved in neurodevelopmental
      processes; mutations affecting the human CNTNAP2 locus are associated with human
      ASD core symptoms, in particular speech and language problems. We demonstrate
      that in Cntnap2-/- mice, no loss of Pvalb neurons is evident in ASD-associated
      brain regions including the striatum, somatosensory cortex (SSC) and medial
      prefrontal cortex (mPFC), shown by the unaltered number of Pvalb neurons
      ensheathed by VVA-positive perineuronal nets. However, the number of PV
      immunoreactive (PV+) neurons and also PV protein levels were decreased in the
      striatum of Cntnap2-/- mice indicating that PV expression levels in some striatal
      Pvalb neurons dropped below the detection limit, yet without a loss of Pvalb
      neurons. No changes in PV+ neuron numbers were detected in the cortical regions
      investigated and also cortical PV expression levels were unaltered. Considering
      that Cntnap2 shows high expression levels in the striatum during human and mouse
      embryonic development and that the cortico-striato-thalamic circuitry is
      important for speech and language development, alterations in striatal PV
      expression and associated (homeostatic) adaptations are likely to play an
      important role in Cntnap2-/- mice and, assumingly, in human ASD patients with
      known Cntnap2 mutations.

PMID- 30116176
TI  - Corrigendum: Regulation of microRNA expression in the neuronal stem cell niches
      during aging of the short-lived annual fish Nothobranchius furzeri.
AB  - [This corrects the article DOI: 10.3389/fncel.2014.00051.].

PMID- 30116175
TI  - Rosuvastatin Reduces Neuroinflammation in the Hemorrhagic Transformation After rt
      PA Treatment in a Mouse Model of Experimental Stroke.
AB  - Hemorrhagic transformation (HT) is a serious complication that stimulates
      inflammation during reperfusion therapy after acute ischemic stroke.
      Rosuvastatin, a 3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase
      inhibitor, might improve the outcome of HT by inhibiting neuroinflammation. This
      study aimed to explore the protective effects of rosuvastatin against HT after
      recombinant tissue plasminogen activator (rt-PA) treatment in mice with
      experimental stroke via the attenuation of inflammation. A total of one hundred
      sixty-nine male BALB/c mice were used in the experiment. HT was successfully
      established in 70 mice that were subjected to 3 h of middle cerebral artery
      occlusion (MCAO) followed by a 10 mg/kg rt-PA injection over 10 min and
      reperfusion for 24 h. The mice were then administered rosuvastatin (1 mg/kg, 5
      mg/kg) or saline (vehicle). The brain water content and neurological deficits
      (wire hang and adhesive removal somatosensory tests) were assessed at 24 h after
      rt-PA reperfusion following MCAO surgery. The morphology, blood-brain barrier
      (BBB) permeability and number of astrocytes and microglia were assessed by
      immunohistochemistry, electron microscopy and western blotting at 24 h after rt
      PA reperfusion following MCAO surgery. Rosuvastatin protected against impaired
      neurological function and reversed the BBB leakage observed in the HT group. The
      increased activation of astrocytes and microglia and secretion of inflammatory
      factors caused by HT damage were significantly attenuated by high-dose
      rosuvastatin treatment vs. normal-dose rosuvastatin treatment. Related
      inflammatory pathways, such as the nuclear factor kappa B (NF-kappaB) and mitogen
      activated protein kinase (MAPK) pathways, were downregulated in the rosuvastatin
      treated groups compared with the HT group. In conclusion, our results indicate
      that rosuvastatin is a promising therapeutic agent for HT after rt-PA reperfusion
      following MCAO surgery in mice, as it attenuates neuroinflammation. Additionally,
      high-dose rosuvastatin treatment could have a greater anti-inflammatory effect on
      HT than normal-dose rosuvastatin treatment.

PMID- 30116173
TI  - Excitatory Dendritic Mitochondrial Calcium Toxicity: Implications for Parkinson's
      and Other Neurodegenerative Diseases.
AB  - Dysregulation of calcium homeostasis has been linked to multiple neurological
      diseases. In addition to excitotoxic neuronal cell death observed following
      stroke, a growing number of studies implicate excess excitatory neuronal activity
      in chronic neurodegenerative diseases. Mitochondria function to rapidly sequester
      large influxes of cytosolic calcium through the activity of the mitochondrial
      calcium uniporter (MCU) complex, followed by more gradual release via calcium
      antiporters, such as NCLX. Increased cytosolic calcium levels almost invariably
      result in increased mitochondrial calcium uptake. While this response may augment
      mitochondrial respiration, limiting classic excitotoxic injury in the short term,
      recent studies employing live calcium imaging and molecular manipulation of
      calcium transporter activities suggest that mitochondrial calcium overload plays
      a key role in Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic
      lateral sclerosis (ALS), and related dementias [PD with dementia (PDD), dementia
      with Lewy bodies (DLB), and frontotemporal dementia (FTD)]. Herein, we review the
      literature on increased excitatory input, mitochondrial calcium dysregulation,
      and the transcriptional or post-translational regulation of mitochondrial calcium
      transport proteins, with an emphasis on the PD-linked kinases LRRK2 and PINK1.
      The impact on pathological dendrite remodeling and neuroprotective effects of
      manipulating MCU, NCLX, and LETM1 are reviewed. We propose that shortening and
      simplification of the dendritic arbor observed in neurodegenerative diseases
      occur through a process of excitatory mitochondrial toxicity (EMT), which
      triggers mitophagy and perisynaptic mitochondrial depletion, mechanisms that are
      distinct from classic excitotoxicity.

PMID- 30116178
TI  - Response: Commentary: Elimination of Left-Right Reciprocal Coupling in the Adult
      Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity.

PMID- 30116177
TI  - Adolescent Isolation Interacts With DISC1 Point Mutation to Impair Adult Social
      Memory and Synaptic Functions in the Hippocampus.
AB  - Disrupted-in-schizophrenia 1 (DISC1) is a strong candidate susceptibility gene
      for a spectrum of neuropsychiatric diseases including schizophrenia, bipolar
      disorder and major depression, all of which are thought to result from
      interactions between gene mutations and environmental risk factors such as
      influenza, trauma and stress. Adolescence is a key period susceptible to stress
      and stress-related mental illnesses. In a previous study, we found that although
      DISC1 L100P point mutation mice shows object recognition deficits, their
      sociability and social memory are relatively normal. Therefore, in this article,
      we investigated whether the interaction between adolescent stress and DISC1 L100P
      point mutation affects adult social memory, and we explored the underlying
      mechanisms. We found that adolescent stress (isolation from 5 weeks to 8 weeks of
      age) specifically impaired social memory of adult DISC1 L100P mice but not that
      of WT littermates, which could be rescued by administration of atypical
      antipsychotic drug clozapine. On the other hand, it did not induce anxiety or
      depression in adult mice. Adolescent isolation exacerbated adult neurogenesis
      deficits in the hippocampus of DISC1 L100P mice, while it had no effect on WT
      mice. In addition, we found that adolescent isolation led to long lasting changes
      in synaptic transmission and plasticity in the hippocampal circuits, some of
      which are specific for DISC1 L100P mice. In summary, we identified here the
      specific interaction between genetic mutation (DISC1 L100P) and adolescence
      social stress that damages synaptic function and social memory in adult
      hippocampal circuits. Highlights -Adolescent isolation (from 5 weeks to 8 weeks
      of age) impairs adult social memory when combined with DISC1 L100P point
      mutation.-Adolescent isolation exacerbates adult neurogenesis deficit in the
      hippocampus of L100P mice but has no similar effect on WT mice.-Adolescent
      isolation causes long lasting changes in synaptic transmission and plasticity of
      the hippocampal network in DISC1 L100P mice.

PMID- 30116179
TI  - Acute MDMA and Nicotine Co-administration: Behavioral Effects and Oxidative
      Stress Processes in Mice.
AB  - 3,4-Methylenedioxy-methylamphetamine (MDMA), a synthetic substance commonly known
      as ecstasy, is a worldwide recreational drug of abuse. As MDMA and nicotine
      activate the same neuronal pathways, we examined the influence of co
      administration of nicotine (0.05 mg/kg) and MDMA (1 mg/kg) on cognitive
      processes, nicotine-induced behavioral sensitization and on processes linked with
      oxidative stress and alpha7 nicotinic acetylcholine receptors (nAChRs) expression
      in the brain of male Swiss mice. For behavioral study the passive avoidance (PA)
      test and locomotor sensitization paradigm were used. Also, the oxidative stress
      parameters as well as expression levels of alpha7 nAChRs in prefrontal cortex and
      hippocampus of mice treated with MDMA alone or in combination with nicotine were
      assessed. The results revealed that MDMA injections as well as co-administrations
      of MDMA and nicotine improved memory consolidation in male Swiss mice tested in
      PA task. Furthermore, one of the main findings of the present study is that MDMA
      increased locomotor activity in nicotine-sensitized mice. Our study showed for
      the first time strong behavioral and biochemical interactions between nicotine
      and MDMA. Both drugs are very often used in combination, especially by young
      people, thus these results may help explaining why psychoactive substances are
      being co-abused and why this polydrug administration is still a social problem.

PMID- 30116180
TI  - Olfactory Memory Impairment Differs by Sex in a Rodent Model of Pediatric
      Radiotherapy.
AB  - Although an effective treatment for pediatric brain tumors, cranial radiation
      therapy (CRT) damages surrounding healthy tissue, thereby disrupting brain
      development. Animal models of pediatric CRT have primarily relied on visual tasks
      to assess cognitive impairment. Moreover, there has been a lack of sex
      comparisons as most research on the cognitive effects of pediatric CRT does not
      include females. Therefore, we utilized olfaction, an ethologically relevant
      sensory modality, to assess cognitive impairment in an animal model of CRT that
      included both male and female mice. Specifically, we used the novel odor
      recognition (NOdorR) task with social odors to test recognition memory, a
      cognitive parameter that has been associated with olfactory neurogenesis, a form
      of cellular plasticity damaged by CRT. In addition to odor recognition memory,
      olfactory ability or discrimination of non-social and social odors were assessed
      both acutely and 3 months after CRT. Magnetic resonance imaging (MRI) and
      histology were performed after behavioral testing to assess long-term damage by
      CRT. Long-term but not acute radiation-induced impairment in odor recognition
      memory was observed, consistent with delayed onset of cognitive impairment in
      human patients. Males showed greater exploration of social odors than females,
      but general exploration was not affected by irradiation. However, irradiated
      males had impaired odor recognition memory in adulthood, compared to non
      irradiated males (or simply male controls). Female olfactory recognition memory,
      in contrast, was dependent on estrus stage. CRT damage was demonstrated by (1)
      histological evaluation of olfactory neurogenesis, which suggested a reduction in
      CRT versus control, and (2) imaging analyses which showed that the majority of
      brain regions were reduced in volume by CRT. Specifically, two regions involved
      in social odor processing (amygdala and piriform cortex) were damaged by cranial
      irradiation in males but not females, paralleling olfactory recognition findings.

PMID- 30116181
TI  - Sleep Deprivation Related Changes of Plasma Oxytocin in Males and Female
      Contraceptive Users Depend on Sex and Correlate Differentially With Anxiety and
      Pain Hypersensitivity.
AB  - Disturbed sleep is known to substantially aggravate both the pain condition and
      the affective state of pain patients. The neurobiological mechanisms underlying
      these adverse effects are unknown. Oxytocin (OT), being largely involved in
      social and emotional behavior, is considered to also play a modulatory role in
      nociception. We hypothesized a pathophysiological role of OT for the hyperalgesic
      and anxiogenic effects of sleep loss. An established human model of one night of
      total sleep deprivation (TSD) was used to test this hypothesis. Twenty young
      healthy students (n = 10 male and n = 10 female) were investigated in a balanced
      cross-over design, contrasting TSD with a night of habitual sleep (HS). All
      females took monophasic oral contraceptives (OC) and were investigated during
      their 'pill-free' phase. Plasma OT concentrations were correlated with (1) pain
      thresholds, (2) descending pain inhibition, and (3) state-anxiety scores.
      Compared to the HS condition, the plasma OT concentration was significantly
      increased in sleep deprived females (p = 0.02) but not males (p = 0.69). TSD
      resulted in pain hypersensitivity to noxious cold (p = 0.05), noxious heat (p =
      0.023), and pricking stimuli (p = 0.013) and significantly increased state
      anxiety (p = 0.021). While, independent of sex, lower heat pain thresholds
      correlated with higher plasma OT (p = 0.036), no such associations were found for
      cold/mechanical pain. In sleep-deprived females, higher plasma OT showed a mild
      (but insignificant) association with lower pain inhibition (p = 0.093). We found
      a positive correlation between anxiety-scores and OT (p = 0.021), which was
      enhanced when respecting "sex" (p = 0.008) and "sleep" (p = 0.001) in a
      hierarchical regression analysis. Altogether, our study revealed a complex and
      partially sex-dependent correlation between plasma OT and TSD-induced changes of
      experimental pain and anxiety. The minor role of OT for TSD-induced changes of
      evoked pain, and its major involvement in anxiety, argues against a specific role
      of OT for linking the adverse effects of TSD on pain sensitivity and anxiety with
      each other. Future investigations are needed in order to dissect out the effect
      of OC on the sex-dependent effects of TSD observed in our study.

PMID- 30116182
TI  - Differential Roles of the Two Raphe Nuclei in Amiable Social Behavior and
      Aggression - An Optogenetic Study.
AB  - Serotonergic mechanisms hosted by raphe nuclei have important roles in
      affiliative and agonistic behaviors but the separate roles of the two nuclei are
      poorly understood. Here we studied the roles of the dorsal (DR) and median raphe
      region (MRR) in aggression by optogenetically stimulating the two nuclei. Mice
      received three 3 min-long stimulations, which were separated by non-stimulation
      periods of 3 min. The stimulation of the MRR decreased aggression in a phasic
      like manner. Effects were rapidly expressed during stimulations, and vanished
      similarly fast when stimulations were halted. No carryover effects were observed
      in the subsequent three trials performed at 2-day intervals. No effects on social
      behaviors were observed. By contrast, DR stimulation rapidly and tonically
      promoted social behaviors: effects were present during both the stimulation and
      non-stimulation periods of intermittent stimulations. Aggressive behaviors were
      marginally diminished by acute DR stimulations, but repeated stimulations
      administered over 8 days considerably decreased aggression even in the absence of
      concurrent stimulations, indicating the emergence of carryover effects. No such
      effects were observed in the case of social behaviors. We also investigated
      stimulation-induced neurotransmitter release in the prefrontal cortex, a major
      site of aggression control. MRR stimulation rapidly but transiently increased
      serotonin release, and induced a lasting increase in glutamate levels. DR
      stimulation had no effect on glutamate, but elicited a lasting increase of
      serotonin release. Prefrontal serotonin levels remained elevated for at least 2 h
      subsequent to DR stimulations. The stimulation of both nuclei increased GABA
      release rapidly and transiently. Thus, differential behavioral effects of the two
      raphe nuclei were associated with differences in their neurotransmission
      profiles. These findings reveal a surprisingly strong behavioral task division
      between the two raphe nuclei, which was associated with a nucleus-specific
      neurotransmitter release in the prefrontal cortex.

PMID- 30116183
TI  - Frontal Alpha Asymmetry and Theta Oscillations Associated With Information
      Sharing Intention.
AB  - Social media has gained increasing importance in many aspects of everyday life,
      from building relationships to establishing collaborative networks between
      individuals worldwide. Sharing behavior is an essential part of maintaining these
      dynamic networks. However, the precise neural factors that could be related to
      sharing behavior in online communities remain unclear. In this study, we recorded
      electroencephalographic (EEG) oscillations of human subjects while they were
      watching short videos. The subjects were later asked to evaluate the videos based
      on how much they liked them and whether they would share them. We found that, at
      the population level, subjects watching videos that would not be shared had
      higher power spectral density (PSD) amplitudes in the theta band (4-8 Hz),
      primarily over the frontal and parietal sites of the right hemisphere, than
      subjects watching videos that would be shared. Previous studies have associated
      task disengagement with an increase in scalp-wide theta activation, which can be
      interpreted as a mind-wandering effect. This might suggest that the decision to
      not share the video may lead to a more automatic/effortless neural pattern. We
      also found that watching videos that would be shared was associated with lower
      PSD amplitudes in the alpha band (8-12 Hz) over the central and right frontal
      sites, and with more negative scores of frontal alpha asymmetry (FAA) index
      scores. These results may be related to previous work linking right-sided frontal
      EEG asymmetry to the pursuit of social conformity and avoidance of negative
      outcomes, such as social isolation. Finally, using support vector machine (SVM)
      algorithms, we show that these EEG parameters and preference rating scores can be
      used to improve the predictability of sharing information behavior. The
      information sharing-related EEG pattern described here could therefore improve
      our understanding of the neural markers associated with sharing behavior and
      contribute to studies about stimuli propagation.

PMID- 30116184
TI  - Promoting Creativity Through Transcranial Direct Current Stimulation (tDCS). A
      Critical Review.
AB  - Creativity, meant as the ability to produce novel, original and suitable ideas,
      has received increased attention by research in the last years, especially from
      neuroaesthetics and social neuroscience. Besides the research conducted on the
      neural correlates of such capacities, previous work tried to answer the question
      of whether it is possible to enhance creativity through cognitive and neural
      stimulation. In particular, transcranial direct current stimulation (tDCS) has
      been applied to increase neuronal excitability in those areas related to
      creativity. However, being a complex construct that applies to a huge variety of
      situations, available results are often confusing and inconsistent. Thus, in the
      present critical review, after selecting original research articles investigating
      creativity with tDCS, results will be reviewed and framed according to the
      different effects of tDCS and its underlying mechanisms, which can be defined as
      follows: the promotion of self-focused attention; the disruption of inhibiting
      mechanisms; the enhancement of creative thinking; the promotion of artistic
      enactment. Finally, a theoretical perspective, the creative on/off model, will be
      provided to integrate the reported evidence with respect to both anatomical and
      functional issues and propose a cognitive explanation of the emergence of
      creative thinking.

PMID- 30116185
TI  - Consciousness and Personhood in Medical Care.
AB  - Current paradigms in Western medicine often fail to differentiate clearly between
      consciousness, responsiveness and personhood. The growing number of individuals
      who exist with sustainable cardiopulmonary systems but who are behaviorally
      unresponsive has prompted a cultural reconsideration of the relationship between
      the presence of consciousness and what it means to be a person. This article
      presents relevant clinical situations that exemplify the different modes in which
      personhood and consciousness can be associated and dissociated: disorders of
      consciousness, emergence from anesthesia, and neocortical death. We draw from
      these examples to call for a reflection on and possible revision of the dominant
      approach towards unresponsive persons to one in which care providers may work
      from the default assumption of the existence of an individual's personhood as
      part of their therapeutic intervention. Behavior consistent with this assumption
      aligns with the principle of respect for persons in the face of the uncertainty
      created by the high rate of misdiagnosis of unconsciousness in unresponsive
      patients and is most consistent with a therapeutic approach to care considering
      evidence suggesting that attributing personhood may in fact evoke consciousness
      in these patients.

PMID- 30116186
TI  - Timing Training in Female Soccer Players: Effects on Skilled Movement Performance
      and Brain Responses.
AB  - Although trainers and athletes consider "good timing skills" critical for optimal
      sport performance, little is known in regard to how sport-specific skills may
      benefit from timing training. Accordingly, this study investigated the effects of
      timing training on soccer skill performance and the associated changes in
      functional brain response in elite- and sub-elite female soccer players. Twenty
      five players (mean age 19.5 years; active in the highest or second highest
      divisions in Sweden), were randomly assigned to either an experimental- or a
      control group. The experimental group (n = 12) was subjected to a 4-week program
      (12 sessions) of synchronized metronome training (SMT). We evaluated effects on
      accuracy and variability in a soccer cross-pass task. The associated brain
      response was captured by functional magnetic resonance imaging (fMRI) while
      watching videos with soccer-specific actions. SMT improved soccer cross-pass
      performance, with a significant increase in outcome accuracy, combined with a
      decrease in outcome variability. SMT further induced changes in the underlying
      brain response associated with observing a highly familiar soccer-specific
      action, denoted as decreased activation in the cerebellum post SMT. Finally,
      decreased cerebellar activation was associated with improved cross-pass
      performance and sensorimotor synchronization. These findings suggest a more
      efficient neural recruitment during action observation after SMT. To our
      knowledge, this is the first controlled study providing behavioral and
      neurophysiological evidence that timing training may positively influence soccer
      skill, while strengthening the action-perception coupling via enhanced
      sensorimotor synchronization abilities, and thus influencing the underlying brain
      responses.

PMID- 30116187
TI  - Formation of Opioid-Induced Memory and Its Prevention: A Computational Study.
AB  - There are several experimental studies which suggest opioids consumption forms
      pathological memories in different brain regions. For example it has been
      empirically demonstrated that the theta rhythm which appears during chronic
      opioid consumption is correlated with the addiction memory formation. In this
      paper, we present a minimal computational model that shows how opioids can change
      firing patterns of the neurons during acute and chronic opioid consumption and
      also during withdrawal periods. The model consists of a pre- and post-synaptic
      neuronal circuits and the astrocyte that monitors the synapses. The output
      circuitry consists of inhibitory interneurons and excitatory pyramidal neurons.
      Our simulation results demonstrate that acute opioid consumption induces
      synchronous patterns in the beta frequency range, while, chronic opioid
      consumption provokes theta frequency oscillations. This allows us to infer that
      the theta rhythm appeared during chronic treatment can be an indication of brain
      engagement in opioid-induced memory formation. Our results also suggest that
      changing the inputs of the interneurons and the inhibitory neuronal network is
      not an appropriate method for preventing the formation of pathological memory.
      However, the same results suggest that prevention of pathological memory
      formation is possible by manipulating the input of the stimulatory network and
      the excitatory connections in the neuronal network. They also show that during
      withdrawal periods, firing rate is reduced and random fluctuations are generated
      in the modeled neural network. The random fluctuations disappear and synchronized
      patterns emerge when the activities of the astrocytic transporters are decreased.
      These results suggest that formation of the synchronized activities can be
      correlated with the relapse. Our model also predicts that reduction in
      gliotransmitter release can eliminate the synchrony and thereby it can reduce the
      likelihood of the relapse occurrence.

PMID- 30116188
TI  - Development of a Parent Wireless Assistive Interface for Myoelectric Prosthetic
      Hands for Children.
AB  - In this study, a one-degree-of-freedom myoelectric prosthesis system was proposed
      using a Parent Wireless Assistive Interface (PWAI) that allowed an external
      assistant (e. g., the parent of the user) to immediately adjust the parameters of
      the prosthetic hand controller. In the PWAI, the myoelectric potential of use of
      the upper limb was plotted on an external terminal in real time. Simultaneously,
      the assistant adjusted the parameters of the prosthetic hand control device and
      manually manipulated the prosthetic hand. With these functions, children that
      have difficulty verbally communicating could obtain properly adjusted prosthetic
      hands. In addition, non-experts could easily adjust and manually manipulate the
      prosthesis; therefore, training for the prosthetic hands could be performed at
      home. Two types of hand motion discrimination methods were constructed in this
      study of the myoelectric control system: (1) a threshold control based on the
      myoelectric potential amplitude information and (2) a pattern recognition of the
      frequency domain features. In an evaluation test of the prosthesis threshold
      control system, child subjects achieved discrimination rates as high as 89%,
      compared with 96% achieved by adult subjects. Furthermore, the high
      discrimination rate was maintained by sequentially updating the threshold value.
      In addition, a discrimination rate of 82% on average was obtained by recognizing
      three motions using the pattern recognition method.

PMID- 30116189
TI  - Inhibitory Effect of Anoectochilus formosanus Extract on Hyperglycemia-Related PD
      L1 Expression and Cancer Proliferation.
AB  - Traditional herb medicine, golden thread (Anoectochilus formosanus Hayata) has
      been used to treat various diseases. Hyperglycemia induces generation of reactive
      oxygen species (ROS) and enhancement of oxidative stress which are risk factors
      for cancer progression and metastasis. In this study, we evaluated hypoglycemic
      effect of A. formosanus extracts (AFEs) in an inducible hyperglycemia animal
      model and its capacity of free-radical scavenging to establish hyperglycemia
      related carcinogenesis. AFE reduced blood glucose in hyperglycemic mice while
      there was no change in control group. The incremental area under blood glucose
      response curve was decreased significantly in hyperglycemic mice treated with AFE
      in a dose-dependent manner. AFE and metformin at the same administrated dose of
      50 mg/kg showed similar effect on intraperitoneal glucose tolerance test in
      hyperglycemic mice. Free-radical scavenger capacity of AFE was concentration
      dependent and 200 MUg/ml of AFE was able to reduce more than 41% of the free
      radical. Treatment of cancer cells with AFE inhibited constitutive PD-L1
      expression and its protein accumulation. It also induced expression of pro
      apoptotic genes but inhibited proliferative and metastatic genes. In addition, it
      induced anti-proliferation in cancer cells. The results suggested that AFE not
      only reduced blood glucose concentration as metformin but also showed its
      potential use in cancer immune chemoprevention/therapy via hypoglycemic effect,
      ROS scavenging and PD-L1 suppression.

PMID- 30116190
TI  - Antibacterial Properties of Medicinal Plants From Pakistan Against Multidrug
      Resistant ESKAPE Pathogens.
AB  - Local people in the Sudhnoti district of Pakistan share a rich practice of
      traditional medicine for the treatment of a variety of ailments. We selected nine
      plants from the Sudhnoti ethnopharmacological tradition used for the treatment of
      infectious and inflammatory disease. Our aim was to evaluate the in vitro anti
      infective potential of extracts from these species against multidrug-resistant
      (MDR) ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
      Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species)
      pathogens. Plant specimens were collected in the Sudhnoti district of Pakistan
      and vouchers deposited in Pakistan and the USA. Dried bulk specimens were ground
      into a fine powder and extracted by aqueous decoction and maceration in ethanol.
      Extracts were assessed for growth inhibitory activity against ESKAPE pathogens
      and biofilm and quorum sensing activity was assessed in Staphylococcus aureus.
      Cytotoxicity to human cells was assessed via a lactate dehydrogenase assay of
      treated human keratinocytes (HaCaTs). Four ethanolic extracts (Zanthoxylum
      armatum, Adiantum capillus-venaris, Artemisia absinthium, and Martynia annua)
      inhibited the growth of MDR strains of ESKAPE pathogens (IC50: 256 MUg mL-1). All
      extracts, with the exception of Pyrus pashia and M. annua, exhibited significant
      quorum quenching in a reporter strain for S. aureus agr I. The ethanolic extract
      of Z. armatum fruits (Extract 1290) inhibited quorum sensing (IC50 32-256 MUg mL
      1) in S. aureus reporter strains for agr I-III. The quorum quenching activity of
      extract 1290 was validated by detection of delta-toxin in the bacterial
      supernatant, with concentrations of 64-256 MUg mL-1 sufficient to yield a
      significant drop in delta-toxin production. None of the extracts inhibited S.
      aureus biofilm formation at sub-inhibitory concentrations for growth. All
      extracts were well tolerated by human keratinocytes (LD50 >= 256 MUg mL-1).
      Chemical analysis of extract 1290 by liquid chromatography-Fourier transform mass
      spectrometry (LC-FTMS) revealed the presence of 29 compounds, including eight
      with putative structural matches. In conclusion, five out of the nine selected
      anti-infective medicinal plants exhibited growth inhibitory activity against at
      least one MDR ESKAPE pathogen at concentrations not harmful to human
      keratinocytes. Furthermore, Z. armatum was identified as a source of quorum
      quenching natural products and further bioassay-guided fractionation of this
      species is merited.

PMID- 30116192
TI  - Relationship Between Gender and the Effectiveness of Montelukast: An
      Italian/Danish Register-Based Retrospective Cohort Study.
AB  - Rationale: Gender-related differences in asthma prevalence, pathophysiology and
      clinical features induced by sex steroids have been investigated, however, how
      gender influences response to asthma treatments in routine clinical practice have
      not yet been elucidated fully. This aspect is crucial for montelukast considering
      the jeopardization of asthmatic patients that benefit from this treatment and the
      existence of evidence of gender differences in leukotriene levels. Therefore, to
      fulfill this medical need, we investigated the role of gender on a set of
      montelukast' effectiveness surrogates in adults and pediatric patients with
      asthma. Methods: The study settings were Napoli 2 Local Health Unit (southern
      Italy) and the entire Danish territory. The study population was composed of
      adult and pediatric patients with asthma. Cumulative incidence curves, unadjusted
      and adjusted Cox regression were used as statistical models to compare
      aforementioned outcomes between genders. Results: Adult Italian male users of
      montelukast had a statistically lower persistence in montelukast treatment
      compared to female users. In the adjusted analyses, they had a higher hazard of
      montelukast' withdrawal (Hazard Ratio [HR] 1.07; 95% Confidence Interval [CI]
      1.01-1.14), add-on/switch to a long-term treatment for asthma following
      montelukast withdrawal (HR 1.72; 95%CI 1.39-2.12), and rescue therapy with short
      acting beta2 agonist (HR 1.24; 95%CI 1.04-1.47). In the adult Danish cohort, we
      also found that male users had higher a hazard of rescue therapy with oral
      corticosteroids (HR 1.10; 95%CI 1.04-1.16). In the pediatric cohorts, no
      statistically significant differences were observed between genders for
      aforementioned outcomes. Conclusions: In adults, male gender was associated with
      increased hazards of montelukast discontinuation, add-on/switch to a long-term
      treatment for asthma following montelukast withdrawal, and rescue therapy with
      oral corticosteroids or short-acting beta2 agonist when compared to the female
      gender. As expected, these associations were reversed or absent in pediatric
      patients.

PMID- 30116193
TI  - UBE2C Is a Potential Biomarker of Intestinal-Type Gastric Cancer With Chromosomal
      Instability.
AB  - This study explored potential biomarkers associated with Lauren classification of
      gastric cancer. We screened microarray datasets on gastric cancer with
      information of Lauren classification in gene expression omnibus (GEO) database,
      and compared differentially expressing genes between intestinal-type or diffuse
      type gastric cancer. Four sets of microarray data (GSE2669, GSE2680, GDS3438, and
      GDS4007) were enrolled into analysis. By differential gene analysis, UBE2C, CDH1,
      CENPF, ERO1L, SCD, SOX9, CKS1B, SPP1, MMP11, and ANLN were identified as the top
      genes related to intestinal-type gastric cancer, and MGP, FXYD1, FAT4, SIPA1L2,
      MUC5AC, MMP15, RAB23, FBLN1, ANXA10, and ADH1B were genes related to diffuse-type
      gastric cancer. We comprehensively validated the biological functions of the
      intestinal-type gastric cancer related gene UBE2C and evaluated its clinical
      significance on 1,868 cases of gastric cancer tissues from multiple medical
      centers of Shanghai, China. The gain of copy number on 20q was found in 4 out of
      5 intestinal-type cancer cell lines, and no similar copy number variation (CNV)
      was found in any diffuse-type cancer cell line. Interfering UBE2C expression
      inhibited cell proliferation, migration and invasion in vitro, and tumorigenesis
      in vivo. Knockdown of UBE2C resulted in G2/M blockage in intestinal-type gastric
      cancer cells. Overexpression of UBE2C activated ERK signal pathway and promoted
      cancer cell proliferation. U0126, an inhibitor of ERK signaling pathway reversed
      the oncogenic phenotypes caused by UBE2C. Moreover, overexpression of UBE2C was
      identified in human intestinal-type gastric cancer. Overexpression of UBE2C
      protein predicted poor clinical outcome. Taken together, we characterized a group
      of Lauren classification-associated biomarkers, and clarified biological
      functions of UBE2C, an intestinal-type gastric cancer associated gene.
      Overexpression of UBE2C resulted in chromosomal instability that disturbed cell
      cycle and led to poor prognosis of intestinal-type gastric cancer.

PMID- 30116194
TI  - Ginsenoside Rg3 Attenuates Lipopolysaccharide-Induced Acute Lung Injury via MerTK
      Dependent Activation of the PI3K/AKT/mTOR Pathway.
AB  - Acute lung injury (ALI) is a common clinical disease with high morbidity in both
      humans and animals. Ginsenoside Rg3, a type of traditional Chinese medicine
      extracted from ginseng, is widely used to cure many inflammation-related
      diseases. However, the specific molecular mechanism of the effects of ginsenoside
      Rg3 on inflammation has rarely been reported. Thus, we established a mouse model
      of lipopolysaccharide (LPS)-induced ALI to investigate the immune protective
      effects of ginsenoside Rg3 and explore its molecular mechanism. In wild type (WT)
      mice, we found that ginsenoside Rg3 treatment significantly mitigated
      pathological damages and reduced myeloperoxidase (MPO) activity as well as the
      production of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-alpha),
      interleukin-1beta (IL-1beta) and interleukin-6 (IL-6); furthermore, the
      production of anti-inflammatory mediators interleukin-10 (IL-10) and transforming
      growth factor-beta (TGF-beta), polarization of M2 macrophages and expression
      levels of the phosphorylation of phosphatidylinositol 3-hydroxy kinase (PI3K),
      protein kinase B (PKB, also known as AKT), mammalian target of rapamycin (mTOR)
      and Mer receptor tyrosine kinase (MerTK) were promoted. However, there were no
      significant differences with regards to the pathological damage, MPO levels,
      inflammatory cytokine levels, and protein expression levels of the
      phosphorylation of PI3K, AKT and mTOR between the LPS treatment group and
      ginsenoside Rg3 group in MerTK-/- mice. Taken together, the present study
      demonstrated that ginsenoside Rg3 could attenuate LPS-induced ALI by decreasing
      the levels of pro-inflammatory mediators and increasing the production of anti
      inflammatory cytokines. These processes were mediated through MerTK-dependent
      activation of its downstream the PI3K/AKT/mTOR pathway. These findings identified
      a new site of the specific anti-inflammatory mechanism of ginsenoside Rg3.

PMID- 30116191
TI  - Biologically Targeted Magnetic Hyperthermia: Potential and Limitations.
AB  - Hyperthermia, the mild elevation of temperature to 40-43 degrees C, can induce
      cancer cell death and enhance the effects of radiotherapy and chemotherapy.
      However, achievement of its full potential as a clinically relevant treatment
      modality has been restricted by its inability to effectively and preferentially
      heat malignant cells. The limited spatial resolution may be circumvented by the
      intravenous administration of cancer-targeting magnetic nanoparticles that
      accumulate in the tumor, followed by the application of an alternating magnetic
      field to raise the temperature of the nanoparticles located in the tumor tissue.
      This targeted approach enables preferential heating of malignant cancer cells
      whilst sparing the surrounding normal tissue, potentially improving the
      effectiveness and safety of hyperthermia. Despite promising results in
      preclinical studies, there are numerous challenges that must be addressed before
      this technique can progress to the clinic. This review discusses these challenges
      and highlights the current understanding of targeted magnetic hyperthermia.

PMID- 30116195
TI  - A Mechanistic Computational Model Reveals That Plasticity of CD4+ T Cell
      Differentiation Is a Function of Cytokine Composition and Dosage.
AB  - CD4+ T cells provide cell-mediated immunity in response to various antigens.
      During an immune response, naive CD4+ T cells differentiate into specialized
      effector T helper (Th1, Th2, and Th17) cells and induced regulatory (iTreg) cells
      based on a cytokine milieu. In recent studies, complex phenotypes resembling more
      than one classical T cell lineage have been experimentally observed. Herein, we
      sought to characterize the capacity of T cell differentiation in response to the
      complex extracellular environment. We constructed a comprehensive mechanistic
      (logical) computational model of the signal transduction that regulates T cell
      differentiation. The model's dynamics were characterized and analyzed under 511
      different environmental conditions. Under these conditions, the model predicted
      the classical as well as the novel complex (mixed) T cell phenotypes that can co
      express transcription factors (TFs) related to multiple differentiated T cell
      lineages. Analyses of the model suggest that the lineage decision is regulated by
      both compositions and dosage of signals that constitute the extracellular
      environment. In this regard, we first characterized the specific patterns of
      extracellular environments that result in novel T cell phenotypes. Next, we
      predicted the inputs that can regulate the transition between the canonical and
      complex T cell phenotypes in a dose-dependent manner. Finally, we predicted the
      optimal levels of inputs that can simultaneously maximize the activity of
      multiple lineage-specifying TFs and that can drive a phenotype toward one of the
      co-expressed TFs. In conclusion, our study provides new insights into the
      plasticity of CD4+ T cell differentiation, and also acts as a tool to design
      testable hypotheses for the generation of complex T cell phenotypes by various
      input combinations and dosages.

PMID- 30116196
TI  - Simulation of Stimulation: Cytokine Dosage and Cell Cycle Crosstalk Driving
      Timing-Dependent T Cell Differentiation.
AB  - Triggering an appropriate protective response against invading agents is crucial
      to the effectiveness of human innate and adaptive immunity. Pathogen recognition
      and elimination requires integration of a myriad of signals from many different
      immune cells. For example, T cell functioning is not qualitatively, but
      quantitatively determined by cellular and humoral signals. Tipping the balance of
      signals, such that one of these is favored or gains advantage on another one, may
      impact the plasticity of T cells. This may lead to switching their phenotypes
      and, ultimately, modulating the balance between proliferating and memory T cells
      to sustain an appropriate immune response. We hypothesize that, similar to other
      intracellular processes such as the cell cycle, the process of T cell
      differentiation is the result of: (i) pleiotropy (pattern) and (ii) magnitude
      (dosage/concentration) of input signals, as well as (iii) their timing and
      duration. That is, a flexible, yet robust immune response upon recognition of the
      pathogen may result from the integration of signals at the right dosage and
      timing. To investigate and understand how system's properties such as T cell
      plasticity and T cell-mediated robust response arise from the interplay between
      these signals, the use of experimental toolboxes that modulate immune proteins
      may be explored. Currently available methodologies to engineer T cells and a
      recently devised strategy to measure protein dosage may be employed to precisely
      determine, for example, the expression of transcription factors responsible for T
      cell differentiation into various subtypes. Thus, the immune response may be
      systematically investigated quantitatively. Here, we provide a perspective of how
      pattern, dosage and timing of specific signals, called interleukins, may
      influence T cell activation and differentiation during the course of the immune
      response. We further propose that interleukins alone cannot explain the phenotype
      variability observed in T cells. Specifically, we provide evidence that the
      dosage of intercellular components of both the immune system and the cell cycle
      regulating cell proliferation may contribute to T cell activation,
      differentiation, as well as T cell memory formation and maintenance. Altogether,
      we envision that a qualitative (pattern) and quantitative (dosage) crosstalk
      between the extracellular milieu and intracellular proteins leads to T cell
      plasticity and robustness. The understanding of this complex interplay is crucial
      to predict and prevent scenarios where tipping the balance of signals may be
      compromised, such as in autoimmunity.

PMID- 30116197
TI  - Is "Preparation for Oxidative Stress" a Case of Physiological Conditioning
      Hormesis?

PMID- 30116198
TI  - A Universal Scaling Relation for Defining Power Spectral Bands in Mammalian Heart
      Rate Variability Analysis.
AB  - Background: Power spectral density (PSD) analysis of the heartbeat intervals in
      the three main frequency bands [very low frequency (VLF), low frequency (LF), and
      high frequency (HF)] provides a quantitative non-invasive tool for assessing the
      function of the cardiovascular control system. In humans, these frequency bands
      were standardized following years of empirical evidence. However, no quantitative
      approach has justified the frequency cutoffs of these bands and how they might be
      adapted to other mammals. Defining mammal-specific frequency bands is necessary
      if the PSD analysis of the HR is to be used as a proxy for measuring the
      autonomic nervous system activity in animal models. Methods: We first describe
      the distribution of prominent frequency peaks found in the normalized PSD of
      mammalian data using a Gaussian mixture model while assuming three components
      corresponding to the traditional VLF, LF and HF bands. We trained the algorithm
      on a database of human electrocardiogram recordings (n = 18) and validated it on
      databases of dogs (n = 17) and mice (n = 8). Finally, we tested it to predict the
      bands for rabbits (n = 4) for the first time. Results: Double-logarithmic
      analysis demonstrates a scaling law between the GMM-identified cutoff frequencies
      and the typical heart rate (HRm): fVLF-LF = 0.0037? HRm0.58 , fLF-HF = 0.0017?
      HRm1.01 and fHFup = 0.0128? HRm0.86 . We found that the band cutoff frequencies
      and Gaussian mean scale with a power law of 1/4 or 1/8 of the typical body mass
      (BMm), thus revealing allometric power laws. Conclusion: Our automated data
      driven approach allowed us to define the frequency bands in PSD analysis of beat
      to-beat time series from different mammals. The scaling law between the band
      frequency cutoffs and the HRm can be used to approximate the PSD bands in other
      mammals.

PMID- 30116199
TI  - Meta-Analysis Results on the Association Between TP53 Codon 72 Polymorphism With
      the Susceptibility to Oral Cancer.
AB  - Objectives: TP53 is an important tumor suppressor gene to maintain genomic
      integrity, and its mutations increase the susceptibility to oral carcinoma.
      Previous published studies have reported the relation of TP53 codon 72
      polymorphism with the risk of oral carcinoma, but the results remain
      controversial and inconclusive. Methods: We therefore utilized meta-analysis
      based on a comprehensive search in PubMed, EMBASE, and Google of Scholar
      databases up to August 19, 2017. Results: Total 3,525 cases and 3,712 controls
      from 21 case-control studies were selected. We found no significant association
      between TP53 codon 72 polymorphism and oral carcinoma susceptibility in all
      genetic contrast models, including subgroup analysis based on control source and
      ethnicity. Furthermore, TP53 codon 72 polymorphism was not significant associated
      with oral carcinoma susceptibility in tobacco or alcohol use, and HPV infection
      status. Our results were confirmed by sensitivity analysis and no publication
      bias was found. Conclusions: Taken together, our data indicate that TP53 codon 72
      polymorphism is not associated with the susceptibility to oral carcinoma.

PMID- 30116200
TI  - Dynamical Analysis of the Regulatory Network Controlling Natural Killer Cells
      Differentiation.
AB  - Many disease fighting strategies have focused on the generation of NK cells,
      since they constitute the main immune barrier against cancer and intracellular
      pathogens such as viruses. Therefore, a predictive model for the development of
      NK cells would constitute a useful tool to test several hypotheses regarding the
      production of these cells during both physiological and pathological conditions.
      Here, we present a boolean network model that reproduces experimental results
      reported on the literature regarding the progressive stages of the development of
      NK cells in wild-type and mutant backgrounds. The model allows for the simulation
      of different conditions, including extracellular micro-environment as well as the
      simulation of genetic alterations. It also describes how NK cell differentiation
      depends on a molecular regulatory network that controls the specification of
      lymphoid lineages, such as T and B cells, which share a common progenitor with
      NKs. Furthermore, the study shows that the structure of the regulatory network
      strongly determines the stability of the expression patterns against
      perturbations.

PMID- 30116202
TI  - Klotho and PPAR Gamma Activation Mediate the Renoprotective Effect of Losartan in
      the 5/6 Nephrectomy Model.
AB  - Renin angiotensin system (RAS) blockade reduces the progression of chronic kidney
      disease (CKD) independently of its antihypertensive effect. Ang II-induced
      fibrosis can be mediated by molecules such as klotho, peroxisome proliferator
      activate receptor gamma (PPAR-gamma), and the Wnt/beta-catenin pathway; however,
      the interaction among these molecules and RAS activation is not completely known.
      The aim of this study was to investigate a possible link between RAS, PPAR-gamma,
      and Klotho in the 5/6 nephrectomy (NX) animals. NX rats presented hypertension
      that was blunted by both losartan and propranolol, however, only losartan was
      able to reduce the expression levels of fibronectin FSP1 and TGF-beta in the
      remnant kidney. The anti-fibrotic Klotho and PPAR-gamma were reduced in the
      remnant kidney, and losartan, but not propranolol, restored their levels. In
      contrast, the profibrotic Wnt 7a and Wnt 3 were upregulated and losartan
      prevented the increase in Wnts. In vitro, Ang II induced a decrease in both
      klotho and in PPAR-gamma in Madin-Darby canine kidney (MDCK) cells, and this
      effect was blunted by losartan. However, klotho expression was increased by
      pioglitazone, an agonist of PPAR-gamma, and suppressed by BADGE, an antagonist of
      PPAR-gamma, suggesting that the effect of Ang II downregulating klotho is
      mediated by PPAR-gamma. These data suggest that activation of the Wnt pathway
      together with downregulation of PPAR-gamma that in turn suppresses klotho
      contribute to potentiating the profibrotic effect of Ang II.

PMID- 30116201
TI  - The Muscle Fiber Profiles, Mitochondrial Content, and Enzyme Activities of the
      Exceptionally Well-Trained Arm and Leg Muscles of Elite Cross-Country Skiers.
AB  - As one of the most physically demanding sports in the Olympic Games, cross
      country skiing poses considerable challenges with respect to both force
      generation and endurance during the combined upper- and lower-body effort of
      varying intensity and duration. The isoforms of myosin in skeletal muscle have
      long been considered not only to define the contractile properties, but also to
      determine metabolic capacities. The current investigation was designed to explore
      the relationship between these isoforms and metabolic profiles in the arms
      (triceps brachii) and legs (vastus lateralis) as well as the range of training
      responses in the muscle fibers of elite cross-country skiers with equally and
      exceptionally well-trained upper and lower bodies. The proportion of myosin heavy
      chain (MHC)-1 was higher in the leg (58 +/- 2% [34-69%]) than arm (40 +/- 3% [24
      57%]), although the mitochondrial volume percentages [8.6 +/- 1.6 (leg) and 9.0
      +/- 2.0 (arm)], and average number of capillaries per fiber [5.8 +/- 0.8 (leg)
      and 6.3 +/- 0.3 (arm)] were the same. In these comparable highly trained leg and
      arm muscles, the maximal citrate synthase (CS) activity was the same. Still, 3
      hydroxy-acyl-CoA-dehydrogenase (HAD) capacity was 52% higher (P < 0.05) in the
      leg compared to arm muscles, suggesting a relatively higher capacity for lipid
      oxidation in leg muscle, which cannot be explained by the different fiber type
      distributions. For both limbs combined, HAD activity was correlated with the
      content of MHC-1 (r2 = 0.32, P = 0.011), whereas CS activity was not. Thus, in
      these highly trained cross-country skiers capillarization of and mitochondrial
      volume in type 2 fiber can be at least as high as in type 1 fibers, indicating a
      divergence between fiber type pattern and aerobic metabolic capacity. The
      considerable variability in oxidative metabolism with similar MHC profiles
      provides a new perspective on exercise training. Furthermore, the clear
      differences between equally well-trained arm and leg muscles regarding HAD
      activity cannot be explained by training status or MHC distribution, thereby
      indicating an intrinsic metabolic difference between the upper and lower body.
      Moreover, trained type 1 and type 2A muscle fibers exhibited similar aerobic
      capacity regardless of whether they were located in an arm or leg muscle.

PMID- 30116203
TI  - Should Exercise Be Prescribed Differently Between Women and Men? An Emphasis on
      Women Diagnosed With Parkinson's Disease.

PMID- 30116204
TI  - Magnitude Assessment of Adult Neurogenesis in the Octopus vulgaris Brain Using a
      Flow Cytometry-Based Technique.
AB  - Adult neurogenesis is widespread among metazoans, it occurs in animals with a
      network nervous system, as cnidarians, and in animals with a complex and
      centralized brain, such as mammals, non-mammalian vertebrates, ecdysozoans, and a
      lophotrochozoan, Octopus vulgaris. Nevertheless, there are important differences
      among taxa, especially in the number of the regions involved and in cell
      proliferation rate during the life-cycle. The comparative evaluation of adult
      neurogenesis among different brain regions is an arduous task to achieve with
      only stereological techniques. However, in Octopus vulgaris we recently confirmed
      the presence of active proliferation in the learning-memory centers, multisensory
      integration centers, and the motor centers of the adult brain. Here, using a flow
      cytometry technique, we provide a method to quantify the active proliferation in
      octopus nervous system using a BrdU in vitro administration without exposing the
      animals to stress or painful injections usually used. This method is in line with
      the current animal welfare regulations regarding cephalopods, and the flow
      cytometry-based technique enabled us to measure adult neurogenesis more quickly
      and reliably than histological techniques, with the additional advantage of
      processing multiple samples in parallel. Flow cytometry is thus an appropriate
      technique for measuring and comparing adult neurogenesis in animals that are in a
      different physiological and/or environmental contexts. A BrdU immunoreactivity
      distribution, to define the neurogenic areas, and the effective penetration in
      vitro of the BrdU is also provided.

PMID- 30116206
TI  - Prevalence of Attention Deficit Hyperactivity Disorder in Detention Settings: A
      Systematic Review and Meta-Analysis.
AB  - Background: Previous studies have reported a high prevalence of attention deficit
      hyperactivity disorder (ADHD) among people living in detention (PLD)
      corresponding to a five- to ten-fold increase compared to the general population.
      Our main study objective was to provide an updated ADHD prevalence rate for PLD,
      including PLD in psychiatric units. Sub-objectives included (i) comparing
      different ways of assessing ADHD, including DSM-5 criteria and (ii) identifying
      which types of PLD are more likely to have ADHD. Methods: We conducted a
      systematic review and meta-analysis following the PRISMA guidelines and the MOOSE
      checklist. PubMed/Medline, PsycINFO, and Web of Sciences were searched combining
      "ADHD" and "prison" keywords and synonyms for articles published between January
      1, 1966 and January 2, 2018. Potential sources of variation to the meta-analytic
      ADHD prevalence rate were investigated using meta-regressions and subgroups
      analyses. Results: The meta-analysis pooled 102 original studies including 69,997
      participants. The adult ADHD prevalence rate was 26.2% (95% confidence interval:
      22.7-29.6). Retrospective assessments of ADHD in childhood were associated with
      an increased prevalence estimate (41.1, 95% confidence interval: 34.9-47.2, p <
      0.001). There was no significant difference in the prevalence estimate between
      screenings and clinical interviews in adulthood. Only three studies used the DSM
      5 definition of ADHD and results were non-significantly different with other DSM
      versions. We found no difference according to participants' characteristics.
      Conclusion: Our results confirmed the high prevalence rate of ADHD among PLD,
      corresponding to a five-fold increase compared to the general population. In
      light of such high ADHD prevalence, our results reinforce the importance of
      addressing this critical public health issue by (i) systematically offering ADHD
      screening and diagnosis to all individuals entering detention, and (ii)
      delivering treatment, monitoring, and care for ADHD during and after detention.
      These strategies may help reduce recidivism and reincarceration, as well as
      violence in detention settings, in addition to improving the health and wellbeing
      of people living in detention. Additionally, our study suggests that using
      screening scales may be a reliable way of assessing ADHD, although caution is
      needed because a complete evaluation by an experienced clinician is required to
      provide a formal diagnosis.

PMID- 30116207
TI  - Cognitive Impairment and Endoplasmic Reticulum Stress Induced by Repeated Short
      Term Sevoflurane Exposure in Early Life of Rats.
AB  - Sevoflurane is one of the most commonly used volatile anaesthetics for children,
      but the safety of prolonged or repeated clinical use of sevoflurane in infants or
      children is controversial. Here, we investigated the effects of sevoflurane on
      rats in early life and the time scale of those effects. Our behavioral results
      indicated that repeated short-term exposure of new-born rats to sevoflurane
      caused learning and memory impairment, while a single exposure of rats to
      sevoflurane was relatively safe. Further mechanistic investigation revealed that
      repeated sevoflurane exposure impaired long-term potentiation (LTP),
      downregulated the expression of certain synaptogenesis-related proteins (GluR1,
      PSD95) and upregulated proteins related to endoplasmic reticulum (ER) stress in
      the hippocampus. An ER stress inhibitor, tauroursodeoxycholic acid (TUDCA),
      reversed the changes in the levels of synaptic plasticity proteins. Our results
      provide new evidence for the clinical concerns regarding repeated sevoflurane
      anesthesia.

PMID- 30116209
TI  - Skew t Mixture Latent State-Trait Analysis: A Monte Carlo Simulation Study on
      Statistical Performance.
AB  - This simulation study assessed the statistical performance of a skew t mixture
      latent state-trait (LST) model for the analysis of longitudinal data. The model
      aims to identify interpretable latent classes with class-specific LST model
      parameters. A skew t-distribution within classes is allowed to account for non
      normal outcomes. This flexible function covers heavy tails and may reduce the
      risk of identifying spurious classes, e.g., in case of outliers. Sample size,
      number of occasions and skewness of the trait variable were varied. Generally,
      parameter estimation accuracy increases with increasing numbers of observations
      and occasions. Larger bias compared to other parameters occurs for parameters
      referring to the skew t-distribution and variances of the latent trait variables.
      Standard error estimation accuracy shows diffuse patterns across conditions and
      parameters. Overall model performance is acceptable for large conditions, even
      though none of the models is free from bias. The application of the skew t
      mixture model in case of large numbers of occasions and observations may be
      possible, but results should be treated with caution. Moreover, the skew t
      approach may be useful for other mixture models.

PMID- 30116208
TI  - Accessing the Inaccessible: Redefining Play as a Spectrum.
AB  - Defining play has plagued researchers and philosophers for years. From describing
      play as an inaccessible concept due to its complexity, to providing checklists of
      features, the field has struggled with how to conceptualize and operationalize
      "play." This theoretical piece reviews the literature about both play and
      learning and suggests that by viewing play as a spectrum - that ranges from free
      play (no guidance or support) to guided play and games (including purposeful
      adult support while maintaining playful elements), we better capture the true
      essence of play and explain its relationship to learning. Insights from the
      Science of Learning allow us to better understand why play supports learning
      across social and academic domains. By changing the lens through which we
      conceptualize play, we account for previous findings in a cohesive way while also
      proposing new avenues of exploration for the field to study the role of learning
      through play across age and context.

PMID- 30116205
TI  - Uncoupling Protein 2 in Cardiovascular Health and Disease.
AB  - Uncoupling protein 2 (UCP2) belongs to the family of mitochondrial anion carrier
      proteins. It uncouples oxygen consumption from ATP synthesis. UCP2 is
      ubiquitously expressed in most cell types to reduce oxidative stress. It is
      tightly regulated at the transcriptional, translational, and post-translational
      levels. UCP2 in the cardiovascular system is being increasingly recognized as an
      important molecule to defend against various stress signals such as oxidative
      stress in the pathology of vascular dysfunction, atherosclerosis, hypertension,
      and cardiac injuries. UCP2 protects against cellular dysfunction through reducing
      mitochondrial oxidative stress and modulation of mitochondrial function. In view
      of the different functions of UCP2 in various cell types that contribute to whole
      body homeostasis, cell type-specific modification of UCP2 expression may offer a
      better approach to help understanding how UCP2 governs mitochondrial function,
      reactive oxygen species production and transmembrane proton leak and how
      dysfunction of UCP2 participates in the development of cardiovascular diseases.
      This review article provided an update on the physiological regulation of UCP2 in
      the cardiovascular system, and also discussed the involvement of UCP2 deficiency
      and associated oxidative stress in the pathogenesis of several common
      cardiovascular diseases. Drugs targeting UCP2 expression and activity might serve
      another effective strategy to ameliorate cardiovascular dysfunction. However,
      more detailed mechanistic study will be needed to dissect the role of UCP2, the
      regulation of UCP2 expression, and the cellular responses to the changes of UCP2
      expression in normal and stressed situations at different stages of
      cardiovascular diseases.

PMID- 30116210
TI  - When Words Hurt: Affective Word Use in Daily News Coverage Impacts Mental Health.
AB  - Media exposure influences mental health symptomology in response to salient
      aversive events, like terrorist attacks, but little has been done to explore the
      impact of news coverage that varies more subtly in affective content. Here, we
      utilized an existing data set in which participants self-reported physical
      symptoms, depressive symptoms, and anxiety symptoms, and completed a potentiated
      startle task assessing their physiological reactivity to aversive stimuli at
      three time points (waves) over a 9-month period. Using a computational
      linguistics approach, we then calculated an average ratio of words with positive
      vs. negative affective connotations for only articles from news sources to which
      each participant self-reported being exposed over the prior 2 weeks at each wave
      of data collection. As hypothesized, individuals exposed to news coverage with
      more negative affective tone over the prior 2 weeks reported significantly
      greater physical and depressive symptoms, and had significantly greater
      physiological reactivity to aversive stimuli.

PMID- 30116211
TI  - The Weight of Emotions in Decision-Making: How Fearful and Happy Facial Stimuli
      Modulate Action Readiness of Goal-Directed Actions.
AB  - Modern theories of behavioral control converge with the idea that goal
      directed/voluntary behaviors are intimately tied to the evaluation of resources.
      Of key relevance in the decision-making processes that underlie action selection
      are those stimuli that bear emotional content. However, even though it is
      acknowledged that emotional information affects behavioral control, the exact way
      in which emotions impact on action planning is largely unknown. To clarify this
      issue, I gave an emotional version of a go/no-go task to healthy participants, in
      which they had to perform the same arm reaching movement when pictures of fearful
      or happy faces were presented, and to withhold it when pictures of faces with
      neutral expressions were presented. This task allows for the investigation of the
      effects of emotional stimuli when they are task-relevant without conflating
      movement planning with target detection and task switching. It was found that
      both the reaction times (RTs) and the percentages of errors increased when the go
      signal was the image of a fearful looking face, as opposed to when the go-signal
      was a happy looking face. Importantly, to control for the role of the features of
      the stimuli, I ran a control task in which the same pictures were shown; however,
      participants had to move/withhold the commanded movement according to gender,
      disregarding the emotional valence. In this context, the differences between RTs
      and error percentages between the fearful and happy faces disappeared. On the one
      hand, these results suggest that fearful facial stimuli are likely to capture and
      hold attention more strongly than faces that express happiness, which could serve
      to increase vigilance for detecting a potential threat in an observer's
      environment. On the other hand, they also suggest that the influence of fearful
      facial stimuli is not automatic, but it depends on the task requirements.

PMID- 30116212
TI  - "Last Supper" Predicts Greater Weight Loss Early in Obesity Treatment, but Not
      Enough to Offset Initial Gains.
AB  - Background: Many participants experience clinically significant fluctuations in
      weight before beginning a behavioral weight loss program. Pre-treatment weight
      gain, often referred to as the "last supper" effect, may limit total weight loss
      from the time of the pre-treatment screening visit and could be an indicator that
      a participant will respond poorly to behavioral intervention. Methods: Data were
      from the weight loss phase of a two-phase weight loss maintenance trial, in which
      178 participants with obesity (screening BMI = 40.5 +/- 6.0 kg/m2, 87.6% female;
      71.3% black) were provided with a 14 week lifestyle intervention that included a
      meal replacement diet. Participants were categorized as having gained >1.15%,
      remained weight stable, or lost >1.15% of initial weight between the pre
      treatment screening visit and the first treatment session (48.7 +/- 29.4 days).
      We first examined whether the weight change groups differed in baseline eating
      characteristics (e.g., emotional eating, self-regulation, craving frequency)
      using one-way ANCOVAs. Linear mixed models were then used to compare weight
      change groups on total weight loss from the screening visit to week 14 and in
      treatment weight loss from weeks 1 to 14. Results: Nearly half of the sample
      (48.9%) gained >1.15% of initial weight during the pre-treatment period (+2.5 +/-
      1.2%); 41.0% remained weight stable (+0.2 +/- 0.6%); and 10.1% lost >1.15% of
      initial weight (-2.2 +/- 0.9%). There were no significant differences between the
      groups in baseline eating characteristics. As measured from the screening weight,
      the weight-gain group had a lower total loss of 6.8%, compared to 7.8% in the
      weight stable group (p = 0.02) and 9.0% in the weight-loss group (p = 0.003). The
      weight-gain group lost more weight in the first 4 weeks of treatment, but in
      treatment losses did not differ among the groups at week 14. Conclusion: Pre
      treatment weight gain was not an indicator of a poor response to a behavioral
      weight loss intervention and was associated with greater weight loss early in
      treatment. However, weight gain during the pre-treatment period may limit the
      total weight loss that participants achieve from the time that they first enroll
      in a weight loss program.

PMID- 30116214
TI  - Corrigendum: Semantic Interference and Facilitation: Understanding the
      Integration of Spatial Distance and Conceptual Similarity During Sentence
      Reading.
AB  - [This corrects the article DOI: 10.3389/fpsyg.2018.00718.].

PMID- 30116213
TI  - Multiple Time Intervals of Visual Events Are Represented as Discrete Items in
      Working Memory.
AB  - Previous studies on time perception and temporal memory have focused primarily on
      single time intervals; it is still unclear how multiple time intervals are
      perceived and maintained in working memory. In the present study, using
      Sternberg's item recognition task, we compared the working memory of multiple
      items with different time intervals and visual textures, for sub- and supra
      second ranges, and investigated the characteristics of working memory
      representation in the framework of the signal detection theory. In Experiments 1
      3, gratings with different spatial frequencies and time intervals were
      sequentially presented as study items, followed by another grating as a probe.
      Participants determined whether the probe matched one of the study gratings, in
      either the temporal dimension or in the visual dimension. The results exhibited
      typical working memory characteristics such as the effects of memory load, serial
      position, and similarity between probe and study gratings, similarly, to the time
      intervals and visual textures. However, there were some differences between the
      two conditions. Specifically, the recency effect for time intervals was smaller,
      or even absent, as compared to that for visual textures. Further, as compared
      with visual textures, sub-second intervals were more likely to be judged as
      remembered in working memory. In addition, we found interactions between visual
      texture memory and time interval memory, and such visual-interval binding
      differed between sub- and supra-second ranges. Our results indicate that multiple
      time intervals are stored as discrete items in working memory, similarly, to
      visual texture memory, but the former might be more susceptible to decay than the
      latter. The differences in the binding between sub- and supra-second ranges imply
      that working memory for sub- and supra-second ranges may differ in the relatively
      higher decision stage.

PMID- 30116216
TI  - Altered Regional Cortical Brain Activity in Healthy Subjects After Sleep
      Deprivation: A Functional Magnetic Resonance Imaging Study.
AB  - Objective: To investigate acute sleep deprivation (SD)-related regional brain
      activity changes and their relationships with behavioral performances. Methods:
      Twenty-two female subjects underwent an MRI scan and an attention network test at
      rested wakefulness (RW) status and after 24 h SD. The amplitude of low-frequency
      fluctuations (ALFF) was used to investigate SD-related regional brain activity
      changes. We used the receiver operating characteristic (ROC) curve to evaluate
      the ability of the ALFF differences in regional brain areas to distinguish the SD
      status from the RW status. We used Pearson correlations to evaluate the
      relationships between the ALFF differences in brain areas and the behavioral
      performances during the SD status. Results: Subjects at the SD status exhibited a
      lower accuracy rate and a longer reaction time relative to the RW status.
      Compared with RW, SD showed significant lower ALFF values in the right cerebellum
      anterior lobe, and higher ALFF areas in the bilateral inferior occipital gyrus,
      left thalamus, left insula, and bilateral postcentral gyrus. The area under the
      curve values of the specific ALFF differences in brain areas were (mean +/- std,
      0.851 +/- 0.045; 0.805-0.93). Further, the ROC curve analysis demonstrated that
      the ALFF differences in those regional brain areas alone discriminated the SD
      status from the RW status with high degrees of sensitivities (82.16 +/- 7.61%; 75
      93.8%) and specificities (81.23 +/- 11.39%; 62.5-93.7%). The accuracy rate showed
      negative correlations with the left inferior occipital gyrus, left thalamus, and
      left postcentral gyrus, and showed a positive correlation with the right
      cerebellum. Conclusions: The ALFF analysis is a potential indicator for detecting
      the excitation-inhibition imbalance of regional cortical activations disturbed by
      acute SD with high performances.

PMID- 30116215
TI  - Pain Perception and Migraine.
AB  - Background: It is well-known that both inter- and intra-individual differences
      exist in the perception of pain; this is especially true in migraine, an elusive
      pain disorder of the head. Although electrophysiology and neuroimaging techniques
      have greatly contributed to a better understanding of the mechanisms involved in
      migraine during recent decades, the exact characteristics of pain threshold and
      pain intensity perception remain to be determined, and continue to be a matter of
      debate. Objective: The aim of this review is to provide a comprehensive overview
      of clinical, electrophysiological, and functional neuroimaging studies
      investigating changes during various phases of the so-called "migraine cycle" and
      in different migraine phenotypes, using pain threshold and pain intensity
      perception assessments. Methods: A systematic search for qualitative studies was
      conducted using search terms "migraine," "pain," "headache," "temporal
      summation," "quantitative sensory testing," and "threshold," alone and in
      combination (subject headings and keywords). The literature search was updated
      using the additional keywords "pain intensity," and "neuroimaging" to identify
      full-text papers written in English and published in peer-reviewed journals,
      using PubMed and Google Scholar databases. In addition, we manually searched the
      reference lists of all research articles and review articles. Conclusion:
      Consistent data indicate that pain threshold is lower during the ictal phase than
      during the interictal phase of migraine or healthy controls in response to
      pressure, cold and heat stimuli. There is evidence for preictal sub-allodynia,
      whereas interictal results are conflicting due to either reduced or no observed
      difference in pain threshold. On the other hand, despite methodological
      limitations, converging observations support the concept that migraine attacks
      may be characterized by an increased pain intensity perception, which normalizes
      between episodes. Nevertheless, future studies are required to longitudinally
      evaluate a large group of patients before and after pharmacological and non
      pharmacological interventions to investigate phases of the migraine cycle,
      clinical parameters of disease severity and chronic medication usage.

PMID- 30116217
TI  - Practical Management of Epileptic Seizures and Status Epilepticus in Adult
      Palliative Care Patients.
AB  - In terminally ill patients, paroxysmal or episodic changes of consciousness,
      movements and behavior are frequent. Due to ambiguous appearance, the correct
      diagnosis of epileptic seizures (ES) and non-epileptic events (NEE) is often
      difficult. Treatment is frequently complicated by the underlying condition, and
      an approach indicated in healthier patients may not always be appropriate in the
      palliative care setting. This article provides recommendations for diagnosis of
      ES and NEE and treatment options for ES in adult palliative care patients,
      including aspects of alternative administration routes for antiepileptic drugs
      such as intranasal, subcutaneous, or rectal application.

PMID- 30116219
TI  - Bilateral Cavernous Carotid Aneurysms: Atypical Presentation of a Rare Cause of
      Mass Effect. A Case Report and a Review of the Literature.
AB  - Bilateral cavernous carotid aneurysms (CCAs) represent a rare medical condition
      that can mimic other disorders. We present a rare case of bilateral CCAs
      simulating an ocular myasthenia. A 76-year-old woman presented with a history of
      fluctuating bilateral diplopia and unilateral ptosis, which led to the suspicion
      of ocular myasthenia. Magnetic resonance imaging (MRI) and magnetic resonance
      angiography (MRA) of the brain showed the presence of large bilateral aneurysms
      of the carotid cavernous tract. After an unsuccessful attempt with steroid
      therapy, the patient underwent endovascular treatment, with mild improvement.
      Bilateral CCAs can cause pupil sparing third nerve palsies and other cranial
      neuropathies which can mimic signs and symptoms of disorders of the neuromuscular
      junction. Therefore, the possibility of a vascular lesion simulating ocular
      myasthenia should be considered especially in older patients.

PMID- 30116218
TI  - Dim Light at Night and Constant Darkness: Two Frequently Used Lighting Conditions
      That Jeopardize the Health and Well-being of Laboratory Rodents.
AB  - The influence of light on mammalian physiology and behavior is due to the
      entrainment of circadian rhythms complemented with a direct modulation of light
      that would be unlikely an outcome of circadian system. In mammals, physiological
      and behavioral circadian rhythms are regulated by the suprachiasmatic nucleus
      (SCN) of the hypothalamus. This central control allows organisms to predict and
      anticipate environmental change, as well as to coordinate different rhythmic
      modalities within an individual. In adult mammals, direct retinal projections to
      the SCN are responsible for resetting and synchronizing physiological and
      behavioral rhythms to the light-dark (LD) cycle. Apart from its circadian
      effects, light also has direct effects on certain biological functions in such a
      way that the participation of the SCN would not be fundamental for this network.
      The objective of this review is to increase awareness, within the scientific
      community and commercial providers, of the fact that laboratory rodents can
      experience a number of adverse health and welfare outcomes attributed to commonly
      used lighting conditions in animal facilities during routine husbandry and
      scientific procedures, widely considered as "environmentally friendly." There is
      increasing evidence that exposure to dim light at night, as well as chronic
      constant darkness, challenges mammalian physiology and behavior resulting in
      disrupted circadian rhythms, neural death, a depressive-behavioral phenotype,
      cognitive impairment, and the deregulation of metabolic, physiological, and
      synaptic plasticity in both the short and long terms. The normal development and
      good health of laboratory rodents requires cyclical light entrainment, adapted to
      the solar cycle of day and night, with null light at night and safe illuminating
      qualities during the day. We therefore recommend increased awareness of the
      limited information available with regards to lighting conditions, and therefore
      that lighting protocols must be taken into consideration when designing
      experiments and duly highlighted in scientific papers. This practice will help to
      ensure the welfare of laboratory animals and increase the likelihood of producing
      reliable and reproducible results.

PMID- 30116221
TI  - LH/FSH Ratio Is Associated With Visceral Adipose Dysfunction in Chinese Women
      Older Than 55.
AB  - No study examined the association of luteinizing hormone to follicular
      stimulating hormone (LH/FSH) ratio with both visceral obesity outside the context
      of polycystic ovary syndrome. Thus, we hypothesized that the LH/FSH ratio was
      associated with visceral adipose accumulation and dysfunction among Chinese women
      older than 55. From 2014 to 2015, a total of 2,525 women aged 55-89 years were
      identified from a cross-sectional survey on the prevalence of metabolic diseases
      and risk factors in East China. Anthropometric indices, biochemical parameters,
      sex hormones and clinical characteristics were measured. Visceral adipose
      accumulation and function were identified by visceral adiposity index (VAI),
      Chinese visceral adiposity index (CVAI) and lipid accumulation product (LAP).
      Linear regression and logistic regression analyses were conducted to explore the
      association. A total of 1,462 (57.9%) participants had visceral obesity. In the
      linear regression, after full adjustment for demographic variables, metabolic
      factors, total testosterone (T), and estradiol (E2), LH/FSH ratio was positively
      associated with all indices estimating visceral obesity [B (95% CI): Log VAI
      0.060 (0.030-0.090), Log CVAI 0.045 (0.029-0.061), Log LAP 0.103 (0.063-0.142),
      all P < 0.001]. Logistic regression analyses showed that the risk of visceral
      obesity increased with increasing LH/FSH ratio after controlling for age and
      smoking [OR (95% CI): 1.99 (1.52, 2.59), P < 0.001]. After further controlling
      for metabolic factors, the association was attenuated but remained significant
      [OR (95% CI): 1.89 (1.42, 2.53), P < 0.001]. The OR of visceral obesity in the
      fully adjusted model was 1.83 (95% CI 1.37, 2.45) (P < 0.001). Thus, high LH/FSH
      ratio was significantly associated with visceral adipose over-accumulation and
      dysfunction in women over 55 years old. This ratio may be an early marker for
      metabolic disorders in Chinese women older than 55, which warrants further
      investigation.

PMID- 30116222
TI  - ArsRS-Dependent Regulation of homB Contributes to Helicobacter pylori Biofilm
      Formation.
AB  - One elusive area in the Helicobacter pylori field is an understanding of why some
      infections result in gastric cancer, yet others persist asymptomatically for the
      life-span of the individual. Even before the genomic era, the high level of
      intraspecies diversity of H. pylori was well recognized and became an intriguing
      area of investigation with respect to disease progression. Of interest in this
      regard is the unique repertoire of over 60 outer membrane proteins (OMPs),
      several of which have been associated with disease outcome. Of these OMPs, the
      association between HomB and disease outcome varies based on the population being
      studied. While the molecular roles for some of the disease-associated OMPs have
      been evaluated, little is known about the role that HomB plays in the H. pylori
      lifecycle. Thus, herein we investigated homB expression, regulation, and
      contribution to biofilm formation. We found that in H. pylori strain G27, homB
      was expressed at a relatively low level until stationary phase. Furthermore, homB
      expression was suppressed at low pH in an ArsRS-dependent manner; mutation of
      arsRS resulted in increased homB transcript at all tested time-points. ArsRS
      regulation of homB appeared to be direct as purified ArsR was able to
      specifically bind to the homB promoter. This regulation, combined with our
      previous finding that ArsRS mutations lead to enhanced biofilm formation, led us
      to test the hypothesis that homB contributes to biofilm formation by H. pylori.
      Indeed, subsequent biofilm analysis using a crystal-violet quantification assay
      and scanning electron microscopy (SEM) revealed that loss of homB from hyper
      biofilm forming strains resulted in reversion to a biofilm phenotype that
      mimicked wild-type. Furthermore, expression of homB in trans from a promoter that
      negated ArsRS regulation led to enhanced biofilm formation even in strains in
      which the chromosomal copy of homB had been deleted. Thus, homB is necessary for
      hyper-biofilm formation of ArsRS mutant strains and aberrant regulation of this
      gene is sufficient to induce a hyper-biofilm phenotype. In summary, these data
      suggest that the ArsRS-dependent regulation of OMPs such as HomB may be one
      mechanism by which ArsRS dictates biofilm development in a pH responsive manner.

PMID- 30116223
TI  - Diel Patterns of Variable Fluorescence and Carbon Fixation of Picocyanobacteria
      Prochlorococcus-Dominated Phytoplankton in the South China Sea Basin.
AB  - The various photosynthetic apparatus and light utilization strategies of
      phytoplankton are among the critical factors that regulate the distribution of
      phytoplankton and primary productivity in the ocean. Active chlorophyll
      fluorescence has been a powerful technique for assessing the nutritional status
      of phytoplankton by studying the dynamics of photosynthesis. Further studies of
      the energetic stoichiometry between light absorption and carbon fixation have
      enhanced understanding of the ways phytoplankton adapt to their niches. To
      explore the ecophysiology of a Prochlorococcus-dominated phytoplankton
      assemblage, we conducted studies of the diel patterns of variable fluorescence
      and carbon fixation by phytoplankton in the oligotrophic South China Sea (SCS)
      basin in June 2017. We found that phytoplankton photosynthetic performance at
      stations SEATS and SS1 were characterized by a nocturnal decrease, dawn maximum,
      and midday decrease of the maximum quantum yield of PSII ( Fv(') / Fm(') , which
      has been denoted as both Fv/Fm and Fv' / Fm' ) in the nutrient-depleted surface
      layer. That these diel patterns of Fv(') / Fm(') were similar to those in the
      tropical Pacific Ocean suggests macro-nutrient and potentially micro-nutrient
      stress. However, the fact that variations were larger in the central basin than
      at the basin's edge implied variability in the degree of nutrient limitation in
      the basin. The estimated molar ratio of gross O2 production to net production of
      carbon (GOP:NPC) of 4.9:1 was similar to ratios reported across the world's
      oceans. The narrow range of the GOP:NPC ratios is consistent with the assumption
      that there is a common strategy for photosynthetic energy allocation by
      phytoplankton. That photo-inactivated photosystems or nonphotochemical quenching
      rather than GOP accounted for most of the radiation absorbed by phytoplankton
      explains why the maximum quantum yield of carbon fixation was rather low in the
      oligotrophic SCS.

PMID- 30116224
TI  - Unraveling the Composition of the Root-Associated Bacterial Microbiota of
      Phragmites australis and Typha latifolia.
AB  - Phragmites australis and Typha latifolia are two macrophytes commonly present in
      natural and artificial wetlands. Roots of these plants engage in interactions
      with a broad range of microorganisms, collectively referred to as the microbiota.
      The microbiota contributes to the natural process of phytodepuration, whereby
      pollutants are removed from contaminated water bodies through plants. The
      outermost layer of the root corpus, the rhizoplane, is a hot-spot for these
      interactions where microorganisms establish specialized aggregates designated
      biofilm. Earlier studies suggest that biofilm-forming members of the microbiota
      play a crucial role in the process of phytodepuration. However, the composition
      and recruitment cue of the Phragmites, and Typha microbiota remain poorly
      understood. We therefore decided to investigate the composition and functional
      capacities of the bacterial microbiota thriving at the P. australis and T.
      latifolia root-soil interface. By using 16S rRNA gene Illumina MiSeq sequencing
      approach we demonstrated that, despite a different composition of the initial
      basin inoculum, the microbiota associated with the rhizosphere and rhizoplane of
      P. australis and T. latifolia tends to converge toward a common taxonomic
      composition dominated by members of the phyla Actinobacteria, Firmicutes,
      Proteobacteria, and Planctomycetes. This indicates the existence of a selecting
      process acting at the root-soil interface of these aquatic plants reminiscent of
      the one observed for land plants. The magnitude of this selection process is
      maximum at the level of the rhizoplane, where we identified different bacteria
      enriched in and discriminating between rhizoplane and rhizosphere fractions in a
      species-dependent and -independent way. This led us to hypothesize that the
      structural diversification of the rhizoplane community underpins specific
      metabolic capabilities of the microbiota. We tested this hypothesis by
      complementing the sequencing survey with a biochemical approach and scanning
      electron microscopy demonstrating that rhizoplane-enriched bacteria have a bias
      for biofilm-forming members. Together, our data will be critical to facilitate
      the rational exploitation of plant-microbiota interactions for phytodepuration.

PMID- 30116220
TI  - Rhythms of Core Clock Genes and Spontaneous Locomotor Activity in Post-Status
      Epilepticus Model of Mesial Temporal Lobe Epilepsy.
AB  - The interaction of Mesial Temporal Lobe Epilepsy (mTLE) with the circadian system
      control is apparent from an oscillatory pattern of limbic seizures, daytime's
      effect on seizure onset and the efficacy of antiepileptic drugs. Moreover,
      seizures per se can interfere with the biological rhythm output, including
      circadian oscillation of body temperature, locomotor activity, EEG pattern as
      well as the transcriptome. However, the molecular mechanisms underlying this
      cross-talk remain unclear. In this study, we systematically evaluated the
      temporal expression of seven core circadian transcripts (Bmal1, Clock, Cry1,
      Cry2, Per1, Per2, and Per3) and the spontaneous locomotor activity (SLA) in post
      status epilepticus (SE) model of mTLE. Twenty-four hour oscillating SLA remained
      intact in post-SE groups although the circadian phase and the amount and
      intensity of activity were changed in early post-SE and epileptic phases. The
      acrophase of the SLA rhythm was delayed during epileptogenesis, a fragmented 24 h
      rhythmicity and extended active phase length appeared in the epileptic phase. The
      temporal expression of circadian transcripts Bmal1, Cry1, Cry2, Per1, Per2, and
      Per3 was also substantially altered. The oscillatory expression of Bmal1 was
      maintained in rats imperiled to SE, but with lower amplitude (A = 0.2) and an
      advanced acrophase in the epileptic phase. The diurnal rhythm of Cry1 and Cry2
      was absent in the early post-SE but was recovered in the epileptic phase. Per1
      and Per2 rhythmic expression were disrupted in post-SE groups while Per3
      presented an arrhythmic profile in the epileptic phase, only. The expression of
      Clock did not display rhythmic pattern in any condition. These oscillating
      patterns of core clock genes may contribute to hippocampal 24 h cycling and,
      consequently to seizure periodicity. Furthermore, by using a pool of samples
      collected at 6 different Zeitgeber Times (ZT), we found that all clock
      transcripts were significantly dysregulated after SE induction, except Per3 and
      Per2. Collectively, altered SLA rhythm in early post-SE and epileptic phases
      implies a possible role for seizure as a nonphotic cue, which is likely linked to
      activation of hippocampal-accumbens pathway. On the other hand, altered temporal
      expression of the clock genes after SE suggests their involvement in the MTLE.

PMID- 30116225
TI  - Population Structure, Antimicrobial Resistance, and Virulence-Associated Genes in
      Campylobacter jejuni Isolated From Three Ecological Niches: Gastroenteritis
      Patients, Broilers, and Wild Birds.
AB  - Campylobacter jejuni is the causal agent of the food-borne infection with the
      highest incidence in Europe. Both poultry and wild birds are a major reservoir.
      To gain insight into the population structure, virulence potential, and
      antimicrobial resistance (AMR), a collection of 150 isolates from three different
      ecological niches (broilers, wild birds, and human patients) was studied. Despite
      the high genetic diversity found, the population structure defined two distinct
      clusters, one formed mostly by broiler and human isolates and another one by most
      wild bird isolates. The ST-21 complex exhibits highest prevalence (in humans and
      broilers), followed by ST-1275 complex (only in wild birds). The ST-48, -45, and 
      354 complexes were found in all three niches, but represent only 22 out of 150
      studied strains. A higher occurrence of AMR and multidrug resistance was detected
      among broiler and human isolates. Moreover, significant differences were found in
      the distribution of certain putative virulence genes. Remarkably, many wild bird
      strains were negative for either cdtA, cdtB, or cdtC from the canonical strain 81
      176, whereas all broiler and human strains were positive. These data suggest that
      the different variants of the cdt genes might be relevant for the efficient
      colonization of certain hosts by C. jejuni. Our study contributes to the
      understanding of the role of the diverse Campylobacter reservoirs in the
      transmission of campylobacteriosis to humans.

PMID- 30116226
TI  - Applications of Bacteriophages in the Treatment of Localized Infections in
      Humans.
AB  - In the recent years, multidrug-resistant bacteria have become a global threat,
      and phage therapy may to be used as an alternative to antibiotics or, at least,
      as a supplementary approach to treatment of some bacterial infections. Here, we
      describe the results of bacteriophage application in clinical practice for the
      treatment of localized infections in wounds, burns, and trophic ulcers, including
      diabetic foot ulcers. This mini-review includes data from various studies
      available in English, as well as serial case reports published in Russian
      scientific literature (with, at least, abstracts accessible in English). Since,
      it would be impossible to describe all historical Russian publications; we
      focused on publications included clear data on dosage and rout of phage
      administration.

PMID- 30116228
TI  - Quantitative Recovery of Viable Lactobacillus paracasei CNCM I-1572 (L. casei
      DG(r)) After Gastrointestinal Passage in Healthy Adults.
AB  - Probiotics are live microorganisms, and viability after transit through the
      gastrointestinal tract (GIT) is considered an inherent property of the health
      benefits of probiotics. The aim of the present study was to quantify the viable
      and total loads of Lactobacillus paracasei DG cells after passage through the GIT
      following the consumption of the probiotic product Enterolactis (L. casei DG(r);
      L. paracasei CNCM I-1572; L. paracasei DG) from drinkable vials by healthy
      adults. We developed a novel method for discriminating and enumerating culturable
      L. paracasei DG cells based on the unique sticky, filamentous phenotype of this
      strain on MRS agar containing vancomycin and kanamycin. The identity of DG was
      also confirmed with strain-specific primers by colony PCR. This method was used
      for a recovery study of the DG strain to quantify viable cells in the fecal
      samples of 20 volunteers during a 1-week probiotic consumption period and a 1
      week follow-up. We isolated L. paracasei DG from at least one fecal sample from
      all the volunteers. The highest concentration of viable DG cells [ranging from
      3.6 to 6.7 log10 colony-forming unit (CFU) per gram of feces] in the feces was
      observed between 4 and 8 days from the beginning of Enterolactis intake and for
      up to 5 days after cessation of intake. As expected, the total DG count
      determined by real-time quantitative PCR (qPCR) was mostly higher than the viable
      DG cells recovered. Viable count experiments, carried out by combining ad hoc
      culture-based discriminative conditions and strain-specific molecular biological
      protocols, unambiguously demonstrated that L. paracasei DG can survive
      gastrointestinal transit in healthy adults when ingested as Enterolactis in
      drinkable vials containing no less than one billion CFU at the end of shelf life.

PMID- 30116229
TI  - Antimicrobial Susceptibility of Environmental Non-O1/Non-O139 Vibrio cholerae
      Isolates.
AB  - Vibrio cholerae serogroups O1 and O139 are the causative agents of cholera
      disease. There are more than 200 serogroups in this species that are termed V.
      cholerae non-O1/non-O139. Non-O1/non-O139 strains can cause gastroenteritis and
      cholera like diarrhea, wound infections, external otitis, and bacteraemia that
      may lead to mortality. Previous antimicrobial susceptibility studies were
      conducted mainly on O1/O139 serogroups and on clinical isolates. Our aim was to
      study and compare the antimicrobial susceptibilities of non-O1/non-O139
      environmental strains isolated from chironomids, fish, and waterfowl. Significant
      differences were found in the antimicrobial susceptibilities between the
      environmental strains that were isolated from three different reservoir habitats.
      Significant increase in minimum inhibitory concentrations (MICs) of ampicillin
      and chloramphenicol was found in chironomid isolates from 2009 compared to those
      from 2005. V. cholerae isolates from different waterfowl species displayed the
      highest MIC values to chloramphenicol and trimethoprim-sulfamethoxazole (SXT),
      while chironomid isolates demonstrated the highest MIC values toward ampicillin.
      Isolates from fish and waterfowl showed high MIC values toward doxycycline. No
      significant differences were found between the MICs of isolates from the
      different waterfowl species. The percentage of antimicrobial resistance among V.
      cholerae isolates from waterfowl was the highest compared to the abundance of
      antimicrobial resistant isolates from chironomids or fish. The antimicrobial
      resistance genes can be carried on mobile genetic elements, thus, waterfowl may
      act as reservoirs for these elements and may spread them all over the globe. Data
      regarding treatment with antimicrobial agents toward V. cholerae non-O1/non-O139
      serogroups is lacking and therefore further studies are needed.

PMID- 30116227
TI  - Bacterial Biomarkers of Marcellus Shale Activity in Pennsylvania.
AB  - Unconventional oil and gas (UOG) extraction, also known as hydraulic fracturing,
      is becoming more prevalent with the increasing use and demand for natural gas;
      however, the full extent of its environmental impacts is still unknown. Here we
      measured physicochemical properties and bacterial community composition of
      sediment samples taken from twenty-eight streams within the Marcellus shale
      formation in northeastern Pennsylvania differentially impacted by hydraulic
      fracturing activities. Fourteen of the streams were classified as UOG+, and
      thirteen were classified as UOG- based on the presence of UOG extraction in their
      respective watersheds. One stream was located in a watershed that previously had
      UOG extraction activities but was recently abandoned. We utilized high-throughput
      sequencing of the 16S rRNA gene to infer differences in sediment aquatic
      bacterial community structure between UOG+ and UOG- streams, as well as correlate
      bacterial community structure to physicochemical water parameters. Although
      overall alpha and beta diversity differences were not observed, there were a
      plethora of significantly enriched operational taxonomic units (OTUs) within UOG+
      and UOG- samples. Our biomarker analysis revealed many of the bacterial taxa
      enriched in UOG+ streams can live in saline conditions, such as Rubrobacteraceae.
      In addition, several bacterial taxa capable of hydrocarbon degradation were also
      enriched in UOG+ samples, including Oceanospirillaceae. Methanotrophic taxa, such
      as Methylococcales, were significantly enriched as well. Several taxa that were
      identified as enriched in these samples were enriched in samples taken from
      different streams in 2014; moreover, partial least squares discriminant analysis
      (PLS-DA) revealed clustering between streams from the different studies based on
      the presence of hydraulic fracturing along the second axis. This study revealed
      significant differences between bacterial assemblages within stream sediments of
      UOG+ and UOG- streams and identified several potential biomarkers for evaluating
      and monitoring the response of autochthonous bacterial communities to potential
      hydraulic fracturing impacts.

PMID- 30116230
TI  - A Novel qPCR Method for Simultaneous Detection and Quantification of Viable
      Pathogenic and Non-pathogenic Vibrio parahaemolyticus (tlh+ , tdh+ , and ureR +
      ).
AB  - Pathogenic and non-pathogenic Vibrio parahaemolyticus strains were simultaneously
      detected and quantified using a novel viable multiplex real-time PCR (novel
      qPCR). We used a new PCR primer and probe, ureR, as a surrogate for detection of
      the toxin trh gene as the primer was better at identifying variant V.
      parahaemolyticus trh strains. The specificity of all primers and probes used in
      this study were validated on three standard strains of V. parahaemolyticus, 42
      clinical strains, 12 wild strains, 4 strains of Vibrio spp., and 4 strains of
      other bacteria. Then, propidium monoazide (PMA) was applied to inhibit DNA of
      dead cell, and the results of PMA optimized treatments were 15 MUM concentration,
      5 min incubation periods, 15 min light exposure periods and 30 RPM rotational
      speed, which resulted in time and cost savings. Pathogenic and non-pathogenic
      strains were quantified using a two-reaction tube method where the tlh, tdh, and
      ureR genes were amplified. Additionally, standard curves with a 7-log dynamic
      range were generated for quantifying viable V. parahaemolyticus and the
      amplification efficiencies were 108.68, 105.17, and 115.61% for tlh+ , tdh+ , and
      ureR + . This novel qPCR accurately monitored V. parahaemolyticus contamination
      rates in shrimps (Penaeus vannamei) and clams (Ruditapes philippinarum) sampled
      from retail stores located in a major district in Shanghai. In conclusion, our
      assay can prioritize the detection and quantification of viable pathogenic V.
      parahaemolyticus and can prove to be a more effective tool for reducing infection
      risks from consumption of seafood in Shanghai.

PMID- 30116231
TI  - Structural Implications of Genotypic Variations in HIV-1 Integrase From Diverse
      Subtypes.
AB  - Human immunodeficiency virus type 1 (HIV-1) integrase (IN) integrates viral DNA
      into the host genome using its 3'-end processing and strand-transfer activities.
      Due to the importance of HIV-1 IN, it is targeted by the newest class of approved
      drugs known as integrase strand transfer inhibitors (INSTIs). INSTIs are
      efficient in maintaining low viral load; however, as with other approved
      antivirals, resistance mutations emerge in patients receiving INSTI-containing
      therapy. As INSTIs are becoming increasingly accessible worldwide, it is
      important to understand the mechanism(s) of INSTI susceptibility. There is strong
      evidence suggesting differences in the patterns and mechanisms of drug resistance
      between HIV-1 subtype B, which dominates in United States, Western Europe and
      Australia, and non-B infections that are most prevalent in countries of Africa
      and Asia. IN polymorphisms and other genetic differences among diverse subtypes
      are likely responsible for these different patterns, but lack of a full-length
      high-resolution structure of HIV-1 IN has been a roadblock in understanding the
      molecular mechanisms of INSTI resistance and the impact of polymorphisms on
      therapy outcome. A recently reported full-length medium-resolution cryoEM
      structure of HIV-1 IN provides insights into understanding the mechanism of
      integrase function and the impact of genetic variation on the effectiveness of
      INSTIs. Here we use molecular modeling to explore the structural impact of IN
      polymorphisms on the IN reaction mechanism and INSTI susceptibility.

PMID- 30116233
TI  - Decreased Rhamnose Metabolic Flux Improved Production of Target Proteins and Cell
      Flocculation in Pichia pastoris.
AB  - Previously, several genes, including LRA1-LRA4 and LRAR, involved in rhamnose
      utilization pathway, were discovered in Pichia pastoris GS115; among them, LRA3
      and LRA4 were considered as key rate-determining step enzymes. A P. pastoris
      expression platform based on the strong rhamnose-inducible promoter P LRA3 did
      not meet the demands of industrial application due to poor production of
      recombinant proteins. To enhance recombinant protein production of this
      expression platform, a genetically engineered strain, P. pastoris GS115m, with
      decreased rhamnose metabolic flux was developed from P. pastoris GS115 by
      replacement of the rhamnose-inducible promoter P LRA4 with another much weaker
      rhamnose-inducible promoter, P LRA2 . Grown in MRH and YPR media using rhamnose
      as the main carbon source, the engineered strain showed decreased growth rate and
      maximal biomass compared with the parental strain. More importantly, grown in
      rhamnose-containing MRH and YPR media, the recombinant engineered strain
      harboring a beta-galactosidase gene lacB, whose expression was regulated by
      rhamnose-inducible P LRA3 , yielded substantial increases, of 2.5- and 1.5-fold,
      respectively, in target protein production over the parental strain.
      Additionally, grown in MRH and YPR media, the engineered strain had remarkable
      cell flocculation and rapid sedimentation with the increasing of cell density,
      providing an effective and convenient separation of the fermentation supernatant
      from strain cells. The engineered strain is a promising expression host for
      industrial production of target proteins due to its advantages over the parental
      strain as follows: (i) improved production of recombinant proteins, and (ii)
      remarkable cell flocculation and rapid sedimentation.

PMID- 30116232
TI  - The Siderophore Piscibactin Is a Relevant Virulence Factor for Vibrio anguillarum
      Favored at Low Temperatures.
AB  - Vibrio anguillarum causes vibriosis, a hemorrhagic septicaemia that affects many
      cultured marine fish species worldwide. Two catechol siderophores, vanchrobactin
      and anguibactin, were previously identified in this bacterium. While
      vanchrobactin is a chromosomally encoded system widespread in all pathogenic and
      environmental strains, anguibactin is a plasmid-encoded system restricted to
      serotype O1 strains. In this work, we have characterized, from a serotype O2
      strain producing vanchrobactin, a novel genomic island containing a cluster of
      genes that would encode the synthesis of piscibactin, a siderophore firstly
      described in the fish pathogen Photobacterium damselae subsp. piscicida. The
      chemical characterization of this siderophore confirmed that some strains of V.
      anguillarum produce piscibactin. An in silico analysis of the available genomes
      showed that this genomic island is present in many of the highly pathogenic V.
      anguillarum strains lacking the anguibactin system. The construction of single
      and double biosynthetic mutants for vanchrobactin and piscibactin allowed us to
      study the contribution of each siderophore to iron uptake, cell fitness, and
      virulence. Although both siderophores are simultaneously produced, piscibactin
      constitute a key virulence factor to infect fish, while vanchrobactin seems to
      have a secondary role in virulence. In addition, a transcriptional analysis of
      the gene cluster encoding piscibactin in V. anguillarum showed that synthesis of
      this siderophore is favored at low temperatures, being the transcriptional
      activity of the biosynthetic genes three-times higher at 18 degrees C than at 25
      degrees C. We also show that iron levels and temperature contribute to balance
      the synthesis of both siderophores.

PMID- 30116234
TI  - Eighteen-Year Farming Management Moderately Shapes the Soil Microbial Community
      Structure but Promotes Habitat-Specific Taxa.
AB  - Soil microbes have critical influence on the productivity and sustainability of
      agricultural ecosystems, yet the magnitude and direction to which management
      practices affect the soil microbial community remain unclear. This work aimed to
      examine the impacts of three farming systems, conventional grain cropping (CON),
      organic grain cropping (ORG), and grain cropping-pasture rotation (ICL), on the
      soil microbial community structure and putative gene abundances of N
      transformations using high-throughput 16S rRNA gene and ITS sequencing
      approaches. Two additional systems, a forest plantation (PF) and an abandoned
      agricultural field subject to natural succession (SUC), were also included for
      better assessment of the soil microbial community in terms of variation scale and
      regulatory importance of management intensity vs. plant type. Farming systems
      significantly affected the biodiversity of soil fungi but not bacteria, with
      Shannon index being the lowest in ORG. Bacterial and fungal communities in three
      cropping systems clustered and separated from those in PF and SUC, suggesting
      that management practices as such played minor roles in shaping the soil
      microbial community compared to plant type (i.e., woody vs. herbaceous plants).
      However, management practices prominently regulated habitat-specific taxa.
      Lecanoromycetes, a class of Ascomycota accounted for ~10% of total fungal
      population in ORG, but almost nil in the other four systems. ORG also enriched
      bacteria belonging to the phyla, Acidobacteria, Actinobacteria, Bacteroidetes,
      Chloroflexi, and Gemmatimonadetes. Further, PICRUSt predicted that N-cycle
      community compositions varied with farming systems; compared to CON, ORG and ICL
      were more divergent from PF and SUC. Soil pH, together with inorganic N,
      extractable organic C, and soil organic C:N ratio explained < 50% of the total
      variations in both bacterial and fungal communities. Our data indicates that
      while moderately affecting the overall structure of the soil microbial community,
      management practices, particularly fertilization and the source of N (synthetic
      vs. organic), were important in regulating the presence and abundance of habitat
      specific taxa.

PMID- 30116235
TI  - Role of Zika Virus prM Protein in Viral Pathogenicity and Use in Vaccine
      Development.
AB  - Recent Zika virus (ZIKV) epidemics necessitate the urgent development of
      effective drugs and vaccines, which can be accelerated by an enhanced
      understanding of ZIKV biology. One of the ZIKV structural proteins, precursor
      membrane (prM), plays an important role in the assembly of mature virions through
      cleavage of prM into M protein. Recent studies have suggested that prM protein
      might be implicated in the neurovirulence of ZIKV. Most vaccines targeting ZIKV
      include prM as the immunogen. Here, we review progress in our understanding of
      ZIKV prM protein and its application in ZIKV vaccine development.

PMID- 30116236
TI  - Real-Time Monitoring of Cancer Cells in Live Mouse Bone Marrow.
AB  - Disseminated tumor cells in the bone marrow environment are the main cause of
      systemic metastasis after curative treatment for major solid tumors. However, the
      detailed biological processes of tumor biology in bone marrow have not been well
      defined in a real-time manner, because of a lack of a proper in vivo experimental
      model thereof. In this study, we established intravital imaging models of the
      bone marrow environment to enable real-time observation of cancer cells in the
      bone marrow. Using these novel imaging models of intact bone marrow and
      transplanted bone marrow of mice, respectively, via two-photon microscopy, we
      could first successfully track and analyze both the distribution and the
      phenotype of cancer cells in bone marrow of live mouse. Therefore, these novel in
      vivo imaging models for the bone marrow would provide a valuable tool to identify
      the biologic processes of cancer cells in a real-time manner in a live animal
      model.

PMID- 30116239
TI  - Corrigendum: The Role of Estrogen Membrane Receptor (G Protein-Coupled Estrogen
      Receptor 1) in Skin Inflammation Induced by Systemic Lupus Erythematosus Serum
      IgG.
AB  - [This corrects the article DOI: 10.3389/fimmu.2017.01723.].

PMID- 30116238
TI  - Reference Intervals of Factor H and Factor H-Related Proteins in Healthy
      Children.
AB  - Complement is activated as part of the innate immune defense against invading
      pathogens. Also, it helps to remove apoptotic debris and immune complexes from
      the circulation. Impaired complement function due to aberrant plasma levels of
      complement proteins may be indicative for complement-mediated diseases or can be
      involved in susceptibility for infections. To determine whether plasma levels are
      abnormal, reference intervals (RIs) are used from adult healthy donors. Since
      many complement-mediated diseases have an onset during childhood, it is important
      to know whether these RIs can be extrapolated to children. RIs of Factor H (FH),
      the crucial fluid-phase regulator, and the FH-related proteins (FHRs), its
      homologous counterparts, are unknown in healthy children. While FH is measured to
      diagnose and monitor therapy of patients with atypical hemolytic uremic syndrome,
      recent studies also implicated increased plasma levels of FHRs in disease. Here,
      we investigated the levels of FH and FHRs in healthy children using recently
      developed specific ELISAs. We found that levels of FH, FHR-2, and FHR-3 were
      equal to those found in healthy adults. Levels of FHR-4A and FHR-5 were lower in
      children than in adults. However, only the FHR-5 levels associated with age. The
      RIs of these FH family proteins now serve to support the interpretation of plasma
      levels in prospective and retrospective studies that can be used for routine
      diagnostic and monitoring purposes including pediatric patient samples.

PMID- 30116237
TI  - Defining Breadth of Hepatitis C Virus Neutralization.
AB  - Extraordinary genetic diversity is a hallmark of hepatitis C virus (HCV).
      Therefore, accurate measurement of the breadth of antibody neutralizing activity
      across diverse HCV isolates is key to defining correlates of immune protection
      against the virus, and essential to guide vaccine development. Panels of HCV
      pseudoparticle (HCVpp) or replication-competent cell culture viruses (HCVcc) can
      be used to measure neutralizing breadth of antibodies. These in vitro assays have
      been used to define neutralizing breadth of antibodies in serum, to characterize
      broadly neutralizing monoclonal antibodies, and to identify mechanisms of HCV
      resistance to antibody neutralization. Recently, larger and more diverse panels
      of both HCVpp and HCVcc have been described that better represent the diversity
      of circulating HCV strains, but further work is needed to expand and standardize
      these neutralization panels.

PMID- 30116240
TI  - Differential Mechanisms of Septic Human Pulmonary Microvascular Endothelial Cell
      Barrier Dysfunction Depending on the Presence of Neutrophils.
AB  - Sepsis is characterized by injury of pulmonary microvascular endothelial cells
      (PMVEC) leading to barrier dysfunction. Multiple mechanisms promote septic PMVEC
      barrier dysfunction, including interaction with circulating leukocytes and PMVEC
      apoptotic death. Our previous work demonstrated a strong correlation between
      septic neutrophil (PMN)-dependent PMVEC apoptosis and pulmonary microvascular
      albumin leak in septic mice in vivo; however, this remains uncertain in human
      PMVEC. Thus, we hypothesize that human PMVEC apoptosis is required for loss of
      PMVEC barrier function under septic conditions in vitro. To assess this
      hypothesis, human PMVECs cultured alone or in coculture with PMN were stimulated
      with PBS or cytomix (equimolar interferon gamma, tumor necrosis factor alpha, and
      interleukin 1beta) in the absence or presence of a pan-caspase inhibitor, Q-VD,
      or specific caspase inhibitors. PMVEC barrier function was assessed by
      transendothelial electrical resistance (TEER), as well as fluoroisothiocyanate
      labeled dextran and Evans blue-labeled albumin flux across PMVEC monolayers.
      PMVEC apoptosis was identified by (1) loss of cell membrane polarity (Annexin V),
      (2) caspase activation (FLICA), and (3) DNA fragmentation [terminal
      deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)]. Septic stimulation
      of human PMVECs cultured alone resulted in loss of barrier function (decreased
      TEER and increased macromolecular flux) associated with increased apoptosis
      (increased Annexin V, FLICA, and TUNEL staining). In addition, treatment of
      septic PMVEC cultured alone with Q-VD decreased PMVEC apoptosis and prevented
      septic PMVEC barrier dysfunction. In septic PMN-PMVEC cocultures, there was
      greater trans-PMVEC macromolecular flux (both dextran and albumin) vs. PMVEC
      cultured alone. PMN presence also augmented septic PMVEC caspase activation
      (FLICA staining) vs. PMVEC cultured alone but did not affect septic PMVEC
      apoptosis. Importantly, pan-caspase inhibition (Q-VD treatment) completely
      attenuated septic PMN-dependent PMVEC barrier dysfunction. Moreover, inhibition
      of caspase 3, 8, or 9 in PMN-PMVEC cocultures also reduced septic PMVEC barrier
      dysfunction whereas inhibition of caspase 1 had no effect. Our data demonstrate
      that human PMVEC barrier dysfunction under septic conditions in vitro (cytomix
      stimulation) is clearly caspase-dependent, but the mechanism differs depending on
      the presence of PMN. In isolated PMVEC, apoptosis contributes to septic barrier
      dysfunction, whereas PMN presence enhances caspase-dependent septic PMVEC barrier
      dysfunction independently of PMVEC apoptosis.

PMID- 30116241
TI  - Spontaneous Remission in Paroxysmal Nocturnal Hemoglobinuria-Return to Health or
      Transition Into Malignancy?
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired syndrome characterized
      by intravascular hemolysis, thrombosis, and bone marrow failure. The disease is
      caused by a mutation in the PIG-A gene that leads to the lack of
      glycosylphosphatidylinositol-anchored complement regulatory molecules CD55 and
      CD59 on affected blood cell surfaces. In previous studies, spontaneous clinical
      remissions have been described. The disease manifestations are very
      heterogeneous, and we wanted to examine if true remissions and disappearance of
      the clone occur. In a follow-up of a nation-wide cohort of 106 Finnish patients
      with a PNH clone, we found six cases, where the clone disappeared or was clearly
      diminished. Two of the patients subsequently developed leukemia, while the other
      four are healthy and in clinical remission. According to our data, spontaneous
      remissions are not as frequent as described earlier. Since the disappearance of
      the PNH cell clone may indicate either a favorable or a poor outcome-remission or
      malignancy-careful clinical monitoring in PNH is mandatory. Nevertheless, true
      remissions occur, and further studies are needed to understand the immunological
      background of this phenomenon and to obtain a better understanding of the natural
      history of the disease.

PMID- 30116244
TI  - Immunogenicity and Protection After Vaccination With a Modified Vaccinia Virus
      Ankara-Vectored Yellow Fever Vaccine in the Hamster Model.
AB  - The highly efficacious live-attenuated 17D yellow fever (YF) vaccine is
      occasionally associated with rare life-threatening adverse events. Modified
      vaccinia virus Ankara (MVA), a non-replicating poxvirus, has been used as a
      vaccine platform to safely deliver various antigens. A MVA-based YF vaccine (MVA
      BN-YF) was tested with and without a non-mineral oil adjuvant in a hamster model
      of lethal YF disease and protective efficacy of this vaccine was compared with
      the 17D vaccine. The vaccine candidate MVA-BN-YF generated a protective response
      in hamsters infected with YFV that was comparable to protection by the live 17D
      vaccine. Similar levels of neutralizing antibody were observed in animals
      vaccinated with either vaccine alone or vaccine with adjuvant. Significant
      improvement in survival, weight change, and serum alanine aminotransferase levels
      were observed in vaccinated hamsters when administered 42 and 14 days prior to
      challenge with Jimenez YF virus (YFV). Neutralizing antibodies induced by MVA-BN
      YF were transferred to naive hamsters prior to virus challenge. Passive
      administration of neutralizing antibody 24 h prior to virus infection resulted in
      significantly improved survival and weight change. A trend toward reduced liver
      enzyme levels was also observed. MVA-BN-YF, therefore, represents a safe
      alternative to vaccination with live-attenuated YFV.

PMID- 30116245
TI  - Genetic Defects in Phosphoinositide 3-Kinase delta Influence CD8+ T Cell
      Survival, Differentiation, and Function.
AB  - Activated phosphoinositide 3-kinase delta syndrome (APDS), also known as p110
      delta-activating mutation causing senescent T cells, lymphadenopathy and
      immunodeficiency (PASLI), is an autosomal dominant primary human immunodeficiency
      (PID) caused by heterozygous gain-of-function mutations in PIK3CD, which encodes
      the p110delta catalytic subunit of PI3K. This recently described PID is
      characterized by diverse and heterogeneous clinical manifestations that include
      recurrent respiratory infections, lymphoproliferation, progressive lymphopenia,
      and defective antibody responses. A major clinical manifestation observed in the
      NIH cohort of patients with PIK3CD mutations is chronic Epstein-Barr virus (EBV)
      and/or cytomegalovirus viremia. Despite uncontrolled EBV infection, many
      APDS/PASLI patients had normal or higher frequencies of EBV-specific CD8+ T
      cells. In this review, we discuss data pertaining to CD8+ T cell function in
      APDS/PASLI, including increased cell death, expression of exhaustion markers, and
      altered killing of autologous EBV-infected B cells, and how these and other data
      on PI3K provide insight into potential cellular defects that prevent clearance of
      chronic infections.

PMID- 30116243
TI  - Protective Regulatory T Cell Immune Response Induced by Intranasal Immunization
      With the Live-Attenuated Pneumococcal Vaccine SPY1 via the Transforming Growth
      Factor-beta1-Smad2/3 Pathway.
AB  - Vaccine effectiveness is mainly determined by the mechanism mediating protection,
      emphasizing the importance of unraveling the protective mechanism for novel
      pneumococcal vaccine development. We previously demonstrated that the regulatory
      T cell (Treg) immune response has a protective effect against pneumococcal
      infection elicited by the live-attenuated pneumococcal vaccine SPY1. However, the
      mechanism underlying this protective effect remains unclear. In this study, a
      short synthetic peptide (P17) was used to downregulate Tregs during immunization
      and subsequent challenges in a mouse model. In immunized mice, increase in immune
      cytokines (IL-12p70, IL-4, IL-5, and IL-17A) induced by SPY1 were further
      upregulated by P17 treatment, whereas the decrease in the infection-associated
      inflammatory cytokine TNF-alpha by SPY1 was reversed. P17 also inhibited the
      increase in the immunosuppressive cytokine IL-10 and inflammatory mediator IL-6
      in immunized mice. More severe pulmonary injuries and more dramatic inflammatory
      responses with worse survival in P17-treated immunized mice indicated the
      indispensable role of the Treg immune response in protection against pneumococcal
      infection by maintaining a balance among acquired immune responses stimulated by
      SPY1. Further studies revealed that the significant elevation of active
      transforming growth factor beta (TGF-beta)1 by SPY1 vaccination activated FOXP3,
      leading to increased frequencies of CD4+CD25+Foxp3+ T cells. Moreover, SPY1
      vaccination elevated the levels of Smad2/3 and phosphor-Smad2/3 and downregulated
      the negative regulatory factor Smad7 in a time-dependent manner during
      pneumococcal infection, and these changes were reversed by P17 treatment. These
      results illustrate that SPY1-stimulated TGF-beta1 induced the generation of SPY1
      specific Tregs via the Smad2/3 signaling pathway. In addition, SPY1-specific
      Tregs may participate in protection via the enhanced expression of PD-1 and CTLA
      4. The data presented here extend our understanding of how the SPY1-induced
      acquired Treg immune response contributes to protection elicited by live
      attenuated vaccines and may be helpful for the evaluation of live vaccines and
      other mucosal vaccine candidates.

PMID- 30116247
TI  - Positive and Negative Regulatory Roles of C-Terminal Src Kinase (CSK) in
      FcepsilonRI-Mediated Mast Cell Activation, Independent of the Transmembrane
      Adaptor PAG/CSK-Binding Protein.
AB  - C-terminal Src kinase (CSK) is a major negative regulator of Src family tyrosine
      kinases (SFKs) that play critical roles in immunoreceptor signaling. CSK is
      brought in contiguity to the plasma membrane-bound SFKs via binding to
      transmembrane adaptor PAG, also known as CSK-binding protein. The recent finding
      that PAG can function as a positive regulator of the high-affinity IgE receptor
      (FcepsilonRI)-mediated mast cell signaling suggested that PAG and CSK have some
      non-overlapping regulatory functions in mast cell activation. To determine the
      regulatory roles of CSK in FcepsilonRI signaling, we derived bone marrow-derived
      mast cells (BMMCs) with reduced or enhanced expression of CSK from wild-type (WT)
      or PAG knockout (KO) mice and analyzed their FcepsilonRI-mediated activation
      events. We found that in contrast to PAG-KO cells, antigen-activated BMMCs with
      CSK knockdown (KD) exhibited significantly higher degranulation, calcium
      response, and tyrosine phosphorylation of FcepsilonRI, SYK, and phospholipase C.
      Interestingly, FcepsilonRI-mediated events in BMMCs with PAG-KO were restored
      upon CSK silencing. BMMCs with CSK-KD/PAG-KO resembled BMMCs with CSK-KD alone.
      Unexpectedly, cells with CSK-KD showed reduced kinase activity of LYN and
      decreased phosphorylation of transcription factor STAT5. This was accompanied by
      impaired production of proinflammatory cytokines and chemokines in antigen
      activated cells. In line with this, BMMCs with CSK-KD exhibited enhanced
      phosphorylation of protein phosphatase SHP-1, which provides a negative feedback
      loop for regulating phosphorylation of STAT5 and LYN kinase activity.
      Furthermore, we found that in WT BMMCs SHP-1 forms complexes containing LYN, CSK,
      and STAT5. Altogether, our data demonstrate that in FcepsilonRI-activated mast
      cells CSK is a negative regulator of degranulation and chemotaxis, but a positive
      regulator of adhesion to fibronectin and production of proinflammatory cytokines.
      Some of these pathways are not dependent on the presence of PAG.

PMID- 30116242
TI  - Natural Killer T Cells and Mucosal-Associated Invariant T Cells in Lung
      Infections.
AB  - The immune system has been traditionally divided into two arms called innate and
      adaptive immunity. Typically, innate immunity refers to rapid defense mechanisms
      that set in motion within minutes to hours following an insult. Conversely, the
      adaptive immune response emerges after several days and relies on the innate
      immune response for its initiation and subsequent outcome. However, the recent
      discovery of immune cells displaying merged properties indicates that this
      distinction is not mutually exclusive. These populations that span the innate
      adaptive border of immunity comprise, among others, CD1d-restricted natural
      killer T cells and MR1-restricted mucosal-associated invariant T cells. These
      cells have the unique ability to swiftly activate in response to non-peptidic
      antigens through their T cell receptor and/or to activating cytokines in order to
      modulate many aspects of the immune response. Despite they recirculate all
      through the body via the bloodstream, these cells mainly establish residency at
      barrier sites including lungs. Here, we discuss the current knowledge into the
      biology of these cells during lung (viral and bacterial) infections including
      activation mechanisms and functions. We also discuss future strategies targeting
      these cell types to optimize immune responses against respiratory pathogens.

PMID- 30116246
TI  - The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted
      Vaccine Delivery.
AB  - Nanocarriers (NC) are very promising tools for cancer immunotherapy. Whereas
      conventional vaccines are based on the administration of an antigen and an
      adjuvant in an independent fashion, nanovaccines can facilitate cell-specific co
      delivery of antigen and adjuvant. Furthermore, nanovaccines can be decorated on
      their surface with molecules that facilitate target-specific antigen delivery to
      certain antigen-presenting cell types or tumor cells. However, the target cell
      specific uptake of nanovaccines is highly dependent on the modifications of the
      nanocarrier itself. One of these is the formation of a protein corona around NC
      after in vivo administration, which may potently affect cell-specific targeting
      and uptake of the NC. Understanding the formation and composition of the protein
      corona is, therefore, of major importance for the use of nanocarriers in vaccine
      approaches. This Mini Review will give a short overview of potential non-specific
      interactions of NC with body fluids or cell surfaces that need to be considered
      for the design of NC vaccines for immunotherapy of cancer.

PMID- 30116248
TI  - Simulation of the Dynamics of Primary Immunodeficiencies in B Cells.
AB  - Primary immunodeficiencies (PIDs) are a group of over 300 hereditary,
      heterogeneous, and mainly rare disorders that affect the immune system. Various
      aspects of immune system and PID proteins and genes have been investigated and
      facilitate systems biological studies of effects of PIDs on B cell physiology and
      response. We reconstructed a B cell network model based on data for the core B
      cell receptor activation and response processes and performed semi-quantitative
      dynamic simulations for normal and B cell PID failure modes. The results for
      several knockout simulations correspond to previously reported molecular studies
      and reveal novel mechanisms for PIDs. The simulations for CD21, CD40, LYN, MS4A1,
      ORAI1, PLCG2, PTPRC, and STIM1 indicated profound changes to major transcription
      factor signaling and to the network. Significant effects were observed also in
      the BCL10, BLNK, BTK, loss-of-function CARD11, IKKB, MALT1, and NEMO, simulations
      whereas only minor effects were detected for PIDs that are caused by
      constitutively active proteins (PI3K, gain-of-function CARD11, KRAS, and NFKBIA).
      This study revealed the underlying dynamics of PID diseases, confirms previous
      observations, and identifies novel candidates for PID diagnostics and therapy.

PMID- 30116250
TI  - Molecular Characterization of the 1-Deoxy-D-Xylulose 5-Phosphate Synthase Gene
      Family in Artemisia annua.
AB  - Artemisia annua produces artemisinin, an effective antimalarial drug. In recent
      decades, the later steps of artemisinin biosynthesis have been thoroughly
      investigated; however, little is known about the early steps of artemisinin
      biosynthesis. Comparative transcriptomics of glandular and filamentous trichomes
      and 13CO2 radioisotope study have shown that the 2-C-methyl-D-erythritol-4
      phosphate (MEP) pathway, rather than the mevalonate pathway, plays an important
      role in artemisinin biosynthesis. In this study, we have cloned three 1-deoxy-D
      xylulose 5-phosphate synthase (DXS) genes from A. annua (AaDXS1, AaDXS2, and
      AaDXS3); the DXS enzyme catalyzes the first and rate-limiting enzyme of the MEP
      pathway. We analyzed the expression of these three genes in different tissues in
      response to multiple treatments. Phylogenetic analysis revealed that each of the
      three DXS genes belonged to a distinct clade. Subcellular localization analysis
      indicated that all three AaDXS proteins are targeted to chloroplasts, which is
      consistent with the presence of plastid transit peptides in their N-terminal
      regions. Expression analyses revealed that the expression pattern of AaDXS2 in
      specific tissues and in response to different treatments, including methyl
      jasmonate, light, and low temperature, was similar to that of artemisinin
      biosynthesis genes. To further investigate the tissue-specific expression pattern
      of AaDXS2, the promoter of AaDXS2 was cloned upstream of the beta-glucuronidase
      gene and was introduced in arabidopsis. Histochemical staining assays
      demonstrated that AaDXS2 was mainly expressed in the trichomes of Arabidopsis
      leaves. Together, these results suggest that AaDXS2 might be the only member of
      the DXS family in A. annua that is involved in artemisinin biosynthesis.

PMID- 30116249
TI  - The p.Arg435His Variation of IgG3 With High Affinity to FcRn Is Associated With
      Susceptibility for Pemphigus Vulgaris-Analysis of Four Different Ethnic Cohorts.
AB  - IgG3 is the IgG subclass with the strongest effector functions among all four IgG
      subclasses and the highest degree of allelic variability among all constant
      immunoglobulin genes. Due to its genetic position, IgG3 is often the first
      isotype an antibody switches to before IgG1 or IgG4. Compared with the other IgG
      subclasses, it has a reduced half-life which is probably connected to a decreased
      affinity to the neonatal Fc receptor (FcRn). However, a few allelic variants
      harbor an amino acid replacement of His435 to Arg that reverts the half-life of
      the resulting IgG3 to the same level as the other IgG subclasses. Because of its
      functional impact, we hypothesized that the p.Arg435His variation could be
      associated with susceptibility to autoantibody-mediated diseases like pemphigus
      vulgaris (PV) and bullous pemphigoid (BP). Using a set of samples from German,
      Turkish, Egyptian, and Iranian patients and controls, we were able to demonstrate
      a genetic association of the p.Arg435His variation with PV risk, but not with BP
      risk. Our results suggest a hitherto unknown role for the function of IgG3 in the
      pathogenesis of PV.

PMID- 30116251
TI  - Faba Bean Cultivation - Revealing Novel Managing Practices for More Sustainable
      and Competitive European Cropping Systems.
AB  - Faba beans are highly nutritious because of their high protein content: they are
      a good source of mineral nutrients, vitamins, and numerous bioactive compounds.
      Equally important is the contribution of faba bean in maintaining the
      sustainability of agricultural systems, as it is highly efficient in the
      symbiotic fixation of atmospheric nitrogen. This article provides an overview of
      factors influencing faba bean yield and quality, and addresses the main biotic
      and abiotic constraints. It also reviews the factors relating to the availability
      of genetic material and the agronomic features of faba bean production that
      contribute to high yield and the improvement of European cropping systems.
      Emphasis is to the importance of using new high-yielding cultivars that are
      characterized by a high protein content, low antinutritional compound content,
      and resistance to biotic and abiotic stresses. New cultivars should combine
      several of these characteristics if an increased and more stable production of
      faba bean in specific agroecological zones is to be achieved. Considering that
      climate change is also gradually affecting many European regions, it is
      imperative to breed elite cultivars that feature a higher abiotic-biotic stress
      resistance and nutritional value than currently used cultivars. Improved
      agronomical practices for faba bean crops, such as crop establishment and plant
      density, fertilization and irrigation regime, weed, pest and disease management,
      harvesting time, and harvesting practices are also addressed, since they play a
      crucial role in both the production and quality of faba bean.

PMID- 30116252
TI  - Dissecting the Genetic Basis Underlying Combining Ability of Plant Height Related
      Traits in Maize.
AB  - Maize plant height related traits including plant height, ear height, and
      internode number are tightly linked with biomass, planting density, and grain
      yield in the field. Previous studies have focused on understanding the genetic
      basis of plant architecture traits per se, but the genetic basis of combining
      ability remains poorly understood. In this study, 328 recombinant inbred lines
      were inter-group crossed with two testers to produce 656 hybrids using the North
      Carolina II mating design. Both of the parental lines and hybrids were evaluated
      in two summer maize-growing regions of China in 2015 and 2016. QTL mapping
      highlighted that 7 out of 16 QTL detected for RILs per se could be simultaneously
      detected for general combining ability (GCA) effects, suggesting that GCA effects
      and the traits were genetically controlled by different sets of loci. Among the
      35 QTL identified for hybrid performance, 57.1% and 28.5% QTL overlapped with
      additive/GCA and non-additive/SCA effects, suggesting that the small percentage
      of hybrid variance due to SCA effects in our design. Two QTL hotspots, located on
      chromosomes 5 and 10 and including the qPH5-1 and qPH10 loci, were validated for
      plant height related traits by Ye478 derivatives. Notably, the qPH5-1 locus could
      simultaneously affect the RILs per se and GCA effects while the qPH10, a major
      QTL (PVE > 10%) with pleiotropic effects, only affected the GCA effects. These
      results provide evidence that more attention should be focused on loci that
      influence combining ability directly in maize hybrid breeding.

PMID- 30116253
TI  - High-Density Mapping of an Adult-Plant Stripe Rust Resistance Gene YrBai in Wheat
      Landrace Baidatou Using the Whole Genome DArTseq and SNP Analysis.
AB  - Stripe rust, caused by the biotrophic fungus Puccinia striiformis f. sp. tritici
      (Pst), is one of the most widespread and destructive wheat diseases worldwide.
      Growing resistant cultivars is an effective approach for controlling this
      disease. However, because host resistance genes were easily overcome by new
      virulent Pst races, there is a continuous demand for identifying new effective
      wheat stripe rust resistance genes and develop closely linked markers for marker
      assisted selection (MAS). Baidatou, an old Chinese wheat landrace, has been grown
      for several decades in Longnan region, Gansu Province, where stripe rust
      epidemics are frequent and severe. In our previous study, a single dominant gene
      YrBai in Baidatou was identified to control the adult-plant resistance (APR) to
      Chinese prevalent Pst race CYR33. And the gene was located on wheat chromosome
      6DS by four polymorphic simple sequence repeat (SSR) and two sequence-related
      amplified polymorphism (SRAP) markers, with the genetic distances of two closely
      linked markers 3.6 and 5.4 cM, respectively. To further confirm the APR gene in
      Baidatou and construct the high-density map for the resistance gene, adult plants
      of F1, F2, F3, and F5:6 populations derived from the cross Mingxian169/Baidatou
      and two parents were inoculated with CYR33 at Yangling field, Shaanxi Province
      during 2014-2015, 2015-2016, and 2016-2017 crop seasons, respectively. The field
      evaluation results indicated that a single dominant gene confers the APR to Pst
      race CYR33 in Baidatou. 92 F3 lines and parents were sequenced using DArTseq
      technology based on wheat GBS1.0 platform, and 31 genetic maps consisted of 2,131
      polymorphic SilicoDArT and 952 SNP markers spanning 4,293.94 cM were constructed.
      Using polymorphic SilicoDArT, SNP markers and infection types (ITs) data of F3
      lines, the gene YrBai was further located in 0.8 cM region on wheat chromosome
      6D. These closely linked markers developed in this study should be useful for MAS
      for Baidatou in crop improvement and map-based clone this gene.

PMID- 30116254
TI  - QTL Alignment for Seed Yield and Yield Related Traits in Brassica napus.
AB  - Worldwide consumption of oil is increasing with the growing population in need
      for edible oil and the expansion of industry using biofuels. Then, demand for
      high yielding varieties of oil crops is always increasing. Brassica napus
      (rapeseed) is one of the most important oil crop in the world, therefore,
      increasing rapeseed yield through breeding is inevitable in order to cater for
      the high demand of vegetable oil and high-quality protein for live stocks.
      Quantitative trait loci (QTL) analysis is a powerful tool to identify important
      loci and which is also valuable for molecular marker assisted breeding. Seed
      yield (SY) is a complex trait that is controlled by multiple loci and is affected
      directly by seed weight, seeds per silique and silique number. Some yield-related
      traits, such as plant height, biomass yield, flowering time, and so on, also
      affect the SY indirectly. This study reports the assembly of QTLs identified for
      seed-yield and yield-related traits in rapeseed, in one unique map. A total of
      972 QTLs for seed-yield and yield-related were aligned into the physical map of
      B. napus Darmor-bzh and 92 regions where 198 QTLs overlapped, could be discovered
      on 16 chromosomes. Also, 147 potential candidate genes were discovered in 65
      regions where 131 QTLs overlapped, and might affect nine different traits. At the
      end, interaction network of candidate genes was studied, and showed nine genes
      that could highly interact with the other genes, and might have more influence on
      them. The present results would be helpful to develop molecular markers for yield
      associated traits and could be used for breeding improvement in B. napus.

PMID- 30116255
TI  - Carbon Gain Limitation Is the Primary Mechanism for the Elevational Distribution
      Limit of Myriophyllum in the High-Altitude Plateau.
AB  - Temperature comprises a major driver for species distribution and physiological
      processes in alpine plants. For all terrestrial plant species tested to date,
      elevation associated decreases in temperature have been observed to influence the
      balance between carbon acquisition and usage; restricting the upper limit of most
      alpine trees (i.e., treeline). However, such a carbon source-sink balance has not
      been tested in any alpine aquatic plants, which is an important component of the
      alpine aquatic ecosystem. The Myriophyllum species inhabits a broad range of
      habitats across the high-altitude plateau. Three Myriophyllum species
      (Myriophyllum spicatum, Myriophyllum verticillatum, and Myriophyllum sibiricum)
      from 12 water bodies at elevational gradients between 2766 and 5111 m were
      collected in the Qinghai-Tibetan Plateau. The late growing seasonal
      concentrations of non-structural carbohydrates (NSC) in the leaves were measured
      to find how high-altitude conditions influence the carbon balance in aquatic
      plants. Regression tree analysis separated the 12 water bodies into two groups
      according to water turbidity (seven water bodies with high turbidity and five
      water bodies with low turbidity). Overall, leaf NSC concentrations (primarily
      starch) decreased significantly with increasing elevation in widely distributed
      M. spicatum and M. verticillatum. Regression tree analysis indicated that water
      turbidity (i.e., shady environment) was a strong determinant of leaf NSC. In the
      low turbidity group (<3.5 NTU), leaf NSC concentrations decreased with increasing
      elevation; however, in the high turbidity group (>3.5 NTU), leaf NSC
      concentrations were low and had no association with elevation. Unlike most recent
      studies in tree species, which show low temperatures limited growth at high
      elevations, our results demonstrated that carbon gain limitation is the primary
      mechanism for the elevational distribution limit of Myriophyllum species in the
      Qinghai-Tibetan Plateau. Moreover, water turbidity moderated the effects of low
      temperature by masking the expected carbon limitation trend. Therefore, at least
      two environmental factors (i.e., temperature and light availability) induced
      photosynthesis decreases might explain the NSC responses for aquatic plants in
      response to elevation.

PMID- 30116256
TI  - Population Genetic Diversity and Clustering Analysis for Chinese Dongxiang Group
      With 30 Autosomal InDel Loci Simultaneously Analyzed.
AB  - In comparison with the most preferred genetic marker utilized in forensic science
      (STR), insertion/deletion analysis possesses further benefits, like absence of
      stutter peak, low mutation rate, and enabling mixed stain analysis. At present, a
      total of 169 unrelated healthy Dongxiang individuals dwelling in Dongxiang
      Autonomous county of Gansu province were recruited in our study to appraise the
      forensic usefulness of the panel including 30 autosomal diallelic genetic
      markers. The insertion allele frequencies were in the range of 0.1598 at HLD 111
      to 0.8550 at HLD 118. The cumulative match of probability and the combined
      probability of exclusion were estimated based on independence of pairwise loci,
      with the values of 3.96 * 10-11 and 0.9886, respectively, which showed tremendous
      potential of this panel to be qualified for forensic personal identification in
      Chinese Dongxiang group. And it could also be used as a complementary tool for
      forensic parentage testing when combined with standard STR genetic markers.
      Furthermore, calculation of the DA distance and Fst values of pairwise
      populations, phylogenetic reconstruction, multidimensional scaling analysis,
      structure clustering analysis were also conducted to probe the genetic
      relationships between Dongxiang group and the other 30 reference populations.
      Results demonstrated that Dongxiang ethnic group might be genetically closer
      related with most Chinese populations involved in our study, especially Tibet
      groups, Xibe group, and several Han populations.

PMID- 30116258
TI  - Incorporating Prior Knowledge of Principal Components in Genomic Prediction.
AB  - Genomic prediction using a large number of markers is challenging, due to the
      curse of dimensionality as well as multicollinearity arising from linkage
      disequilibrium between markers. Several methods have been proposed to solve these
      problems such as Principal Component Analysis (PCA) that is commonly used to
      reduce the dimension of predictor variables by generating orthogonal variables.
      Usually, the knowledge from PCA is incorporated in genomic prediction, assuming
      equal variance for the PCs or a variance proportional to the eigenvalues, both
      treat variances as fixed. Here, three prior distributions including normal,
      scaled-t and double exponential were assumed for PC effects in a Bayesian
      framework with a subset of PCs. These developed PCR models (dPCRm) were compared
      to routine genomic prediction models (RGPM) i.e., ridge and Bayesian ridge
      regression, BayesA, BayesB, and PC regression with a subset of PCs but PC
      variances predefined as proportional to the eigenvalues (PCR-Eigen). The
      performance of methods was compared by simulating a single trait with
      heritability of 0.25 on a genome consisted of 3,000 SNPs on three chromosomes and
      QTL numbers of 15, 60, and 105. After 500 generations of random mating as the
      historical population, a population was isolated and mated for another 15
      generations. The generations 8 and 9 of recent population were used as the
      reference population and the next six generations as validation populations. The
      accuracy and bias of predictions were evaluated within the reference population,
      and each of validation populations. The accuracies of dPCRm were similar to RGPM
      (0.536 to 0.664 vs. 0.542 to 0.671), and higher than the accuracies of PCR-Eigen
      (0.504 to 0.641) within reference population over different QTL numbers. Decline
      in accuracies in validation populations were from 0.633 to 0.310, 0.639 to 0.313,
      and 0.617 to 0.298 using dPCRm, RGPM and PCR-Eigen, respectively. Prediction
      biases of dPCRm and RGPM were similar and always much less than biases of PCR
      Eigen. In conclusion assuming PC variances as random variables via prior
      specification yielded higher accuracy than PCR-Eigen and same accuracy as RGPM,
      while fewer predictors were used.

PMID- 30116259
TI  - Synthesis of N-Tetradecyl-1,10-phenathrolinium-Based New Salts for Biological
      Applications.
AB  - New organic salts were synthesized by quaternizing 1,10-phenanthroline using 1
      bromotetradecane. The first step yielded an organic salt of formula [C26H37N2]Br.
      Anion exchange reaction using Li[(CF3SO2)2N] resulted in a more stable salt of
      formula [C26H37N2][(CF3SO2)2N]. The organic salts were investigated by
      spectrometry (1H, 13C, 19F NMR, X-ray photoelectron spectroscopy (XPS), UV-Vis,
      and matrix-assisted laser desorption/ionization mass spectroscopy (MALDI MS),
      CHNSBr elemental analysis, and thermal analysis (TGA and DSC). The thermal
      characterization showed the melting and decomposition points of
      [C26H37N2][(CF3SO2)2N] to be 48 degrees C and 290 degrees C, respectively, which
      indicates it is an ionic liquid with large liquidus range. The biological
      activities of the salts were investigated against two Gram-positive
      (Staphylococcus aureus and Streptococcus pyogenes) and two Gram-negative
      (Escherichia coli and Klebsiella pneumoniae) bacteria, and they are found to be
      active against all of them. They were compared with [Cu(1,10
      phenanthroline)2Cl]Cl. They are found more active against the Gram-negative
      bacteria. The salts demonstrated minimum inhibitory concentration as low as 50
      ug/L. These results suggest the synthesized salts can be considered as a better
      alternative to certain transition metal complex drugs. This minimizes the concern
      of introducing metal ions into the organism.

PMID- 30116257
TI  - Elucidating the Underlying Functional Mechanisms of Breast Cancer Susceptibility
      Through Post-GWAS Analyses.
AB  - Genome-wide association studies (GWAS) have identified more than 170 single
      nucleotide polymorphisms (SNPs) associated with the susceptibility to breast
      cancer. Together, these SNPs explain 18% of the familial relative risk, which is
      estimated to be nearly half of the total familial breast cancer risk that is
      collectively explained by low-risk susceptibility alleles. An important aspect of
      this success has been the access to large sample sizes through collaborative
      efforts within the Breast Cancer Association Consortium (BCAC), but also
      collaborations between cancer association consortia. Despite these achievements,
      however, understanding of each variant's underlying mechanism and how these SNPs
      predispose women to breast cancer remains limited and represents a major
      challenge in the field, particularly since the vast majority of the GWAS
      identified SNPs are located in non-coding regions of the genome and are merely
      tags for the causal variants. In recent years, fine-scale mapping studies
      followed by functional evaluation of putative causal variants have begun to
      elucidate the biological function of several GWAS-identified variants. In this
      review, we discuss the findings and lessons learned from these post-GWAS analyses
      of 22 risk loci. Identifying the true causal variants underlying breast cancer
      susceptibility and their function not only provides better estimates of the
      explained familial relative risk thereby improving polygenetic risk scores
      (PRSs), it also increases our understanding of the biological mechanisms
      responsible for causing susceptibility to breast cancer. This will facilitate the
      identification of further breast cancer risk alleles and the development of
      preventive medicine for those women at increased risk for developing the disease.

PMID- 30116260
TI  - Fucosterol Protects against Concanavalin A-Induced Acute Liver Injury: Focus on
      P38 MAPK/NF-kappaB Pathway Activity.
AB  - Objective: Fucosterol is derived from the brown alga Eisenia bicyclis and has
      various biological activities, including antioxidant, anticancer, and
      antidiabetic properties. The aim of this study was to investigate the protective
      effects of fucosterol pretreatment on Concanavalin A- (ConA-) induced acute liver
      injury in mice, and to understand its molecular mechanisms. Materials and
      Methods: Acute liver injury was induced in BALB/c mice by ConA (25 mg/kg), and
      fucosterol (dissolved in 2% DMSO) was orally administered daily at doses of 25,
      50, and 100 mg/kg. The levels of hepatic necrosis, apoptosis, and autophagy
      associated with inflammatory cytokines were measured at 2, 8, and 24 h. Results:
      Fucosterol attenuated serum liver enzyme levels and hepatic necrosis and
      apoptosis induced by TNF-alpha, IL-6, and IL-1beta. Fucosterol also inhibited
      apoptosis and autophagy by upregulating Bcl-2, which decreased levels of
      functional Bax and Beclin-1. Furthermore, reduced P38 MAPK and NF-kappaB
      signaling were accompanied by PPARgamma activation. Conclusion: This study showed
      that fucosterol could alleviate acute liver injury induced by ConA by inhibiting
      P38 MAPK/PPARgamma/NF-kappaB signaling. These findings highlight that fucosterol
      is a promising potential therapeutic agent for acute liver injury.

PMID- 30116262
TI  - Hemobilia: Perspective and Role of the Advanced Endoscopist.
AB  - Hemobilia refers to bleeding from and/or into the biliary tract and is an
      uncommon cause of gastrointestinal hemorrhage. Hemobilia has been documented
      since the 1600s, but due to its relative rarity, it has only been more critically
      examined in recent decades. Most cases of hemobilia are iatrogenic and caused by
      procedures involving the liver, pancreas, bile ducts, and/or the
      hepatopancreatobiliary vasculature, with trauma and malignancy representing the
      two other major causes. A classic triad of right upper quadrant pain, jaundice,
      and overt upper gastrointestinal bleeding has been described, but this is present
      in only 25-30% of patients with hemobilia. Historically, the gold standard for
      diagnosis and treatment has been angiography and interventional radiologic
      intervention, respectively. However, the paradigm is shifting, at least in select
      cases, towards first-line reliance on noninvasive imaging (e.g., computed
      tomography) and therapeutic endoscopy, owing to advances in and the less invasive
      nature of both, while saving interventional radiological and/or surgical
      intervention for refractory or imminently life-threatening cases.

PMID- 30116261
TI  - Significance of Preoperative Systemic Immune Score for Stage I Gastric Cancer
      Patients.
AB  - Background: Determining preferences regarding the benefits of adjuvant
      chemotherapy (AC) for stage I GC is critical. Methods: We retrospectively
      reviewed 1069 patients with pathologically confirmed stage I GC who underwent R0
      gastrectomy between 2006 and 2014. Univariate and multivariate survival analyses
      were conducted. Systemic inflammation factors were used to develop a scoring
      system for predicting AC benefits. Results: With a median follow-up of 47 months
      (range 3-113 months), the 5-year overall survival (OS) rate was 90.5%. The
      patient score was 1 for either a pretreatment hypoalbuminemia or elevated derived
      neutrophil-lymphocyte ratio (dNLR) and was 0 otherwise. The SIS served as an
      independent prognostic factor for reduced OS. AC was delivered to 13.5%
      (144/1069) of all patients. Compared to surgery alone, AC had no significant
      effect on survival in both the entire cohort and the IA/IB subgroup. However, in
      the high-risk group (SIS = 2), patients with AC had a significantly better OS
      than those undergoing surgery alone. Conclusions: Patients with SIS = 2 may
      benefit from AC and thus may be considered candidates for adjuvant treatment.
      However, to confirm our findings, future prospective studies are warranted.

PMID- 30116263
TI  - Additional Thirty Seconds Observation with Linked Color Imaging Improves
      Detection of Missed Polyps in the Right-Sided Colon.
AB  - Background and Aims: Missed polyps are a pitfall of colonoscopy. In this study,
      we analyzed the efficacy of an additional 30 seconds observation using linked
      color imaging (LCI) for detecting adenoma and sessile serrated adenoma/polyp
      (SSA/P). Materials and Methods: We enrolled patients undergoing colonoscopy from
      February to October 2017 in two institutions. In all patients, the cecum and
      ascending colon were observed with white light imaging (WLI) first. The
      colonoscope was inserted again, and the cecum and ascending colon were observed
      for an additional 30 seconds using either LCI or WLI. The method for the 30 sec
      observation was to insufflate the cecum and ascending colon sufficiently and
      observe them in a distant view, because the length of the second observation was
      determined to be precisely 30 sec. For the second observation, LCI was performed
      for the first 65 patients and WLI for the next 65. Adenoma and SSA/P detection
      rate (ASDR) in the second observation were examined in both groups. According to
      a pilot study, the sample size was estimated 65. Results: In the first
      observation, ASDR were 30.7% in the LCI group and 32.2% in the WLI group (p =
      0.85). For the second observation, 13 polyps were detected in the LCI group and 5
      polyps in the WLI group (p = 0.04). Additionally, ASDR for the second observation
      were 18.5% and 6.1%, respectively (p = 0.03). There were no significant
      differences between the LCI and WLI groups with respect to morphology (ratio of
      polypoid) (38.5% versus 60.0%, p = 0.52) and histology (ratio of adenoma) (92.3%
      versus 100.0%, p = 0.91). Total adenoma and SSA/P number were 48 in the LCI group
      and 36 in the WLI group (p = 0.02). Conclusion: The 30 seconds additional
      observation with LCI improved the detection of adenoma and SSA/P in the right
      sided colon.

PMID- 30116265
TI  - Endoscopic Dilation with Bougies versus Balloon Dilation in Esophageal Benign
      Strictures: Systematic Review and Meta-Analysis.
AB  - Background: The use of bougies and balloons to dilate benign esophageal
      strictures (BES) is a consolidated procedure. However, the amount of evidence
      available in scientific literature supporting which is the best technique is very
      low, despite the great prevalence and importance of such pathology. This
      systematic review with meta-analysis aims at comparing both techniques, providing
      good quality of evidence. Methods: We searched for randomized clinical trials
      (RCTs) published from insertion to November 2017, using MEDLINE, EMBASE, Cochrane
      Central Register of Controlled Trials, LILACS, and grey literature. After the
      data extraction, a meta-analysis was performed. The main outcomes were
      symptomatic relief and recurrence rate. The secondary outcomes were bleeding,
      perforation, and postprocedure pain. Results: We included 5 randomized clinical
      trials (RCTs), totalizing 461 patients. Among them, 151 were treated with bougie
      dilation and 225 underwent balloon dilation. Regarding symptomatic relief,
      recurrence, bleeding, and perforation rates, there were no differences between
      the methods. Concerning postprocedure pain, patients submitted to balloon
      dilation had less intense pain (RD 0.27, 95% IC -0.42 to -0.07, P = 0.007).
      Conclusion: We conclude that there is no difference between bougie and balloon
      dilation of BESs regarding symptomatic relief, recurrence rate at 12 months,
      bleeding, and perforation. Patients undergoing balloon dilation present less
      severe postprocedure pain.

PMID- 30116264
TI  - Analysis of Prognostic Factors for Resected Synchronous and Metachronous Liver
      Metastases from Colorectal Cancer.
AB  - Background: Surgical treatment is the cornerstone in the management of colorectal
      cancer (CRC) liver metastases. The aim of this study is to identify
      clinicopathological factors affecting disease-free (DFS) and overall survival
      (OS) in patients undergoing potentially curative liver resection for CRC
      metastasis. Methods: All consecutive patients undergoing liver resection for
      first recurrence of CRC from February 2006 to February 2018 were included.
      Prognostic impact of factors related to the patient, primary and metastatic
      tumors, was retrospectively tested through univariate and multivariate analyses.
      Results: Seventy patients were included in the study. Median postoperative follow
      up was 37 months (range 1-119). Median DFS and OS were 15.2 and 62.7 months, and
      5-year DFS and OS rates were 16% and 53%. In univariate analysis, timing of
      metastasis presentation/treatment (combined colorectal and liver resection,
      "bowel first" approach or metachronous presentation) (p < 0.0001), ASA score (p =
      0.003), chemotherapy after liver surgery (p = 0.028), T stage (p = 0.021), number
      of resected liver lesions (p < 0.0001), and liver margin status (p = 0.032) was
      significantly associated with DFS while peritoneal resection at colorectal
      surgery (p = 0.026), ASA score (p = 0.036), extension of liver resection (p =
      0.024), chemotherapy after liver surgery (p = 0.047), and positive nodes (p =
      0.018) with OS. In multivariate analysis, timing of metastasis
      presentation/treatment, ASA score, and chemotherapy (before and after liver
      surgery) resulted significantly associated with DFS and timing of metastasis
      presentation/treatment, positive nodes, peritoneal resection at colorectal
      surgery, and surgical approach (open or minimally invasive) of colorectal
      resection with OS. Conclusions: Surgery may provide good DFS and OS rates for CRC
      liver metastasis. Patient selection for surgery and correct timing of
      intervention within a multidisciplinary approach may be improved by taking into
      account negative prognostic factors which stress the importance of systemic
      therapy.

PMID- 30116266
TI  - Systematic Review with Network Meta-Analysis: Efficacy of Induction Therapy with
      a Second Biological Agent in Anti-TNF-Experienced Crohn's Disease Patients.
AB  - Background and Aim: Crohn's disease (CD) is a chronic inflammatory condition of
      the gastrointestinal tract with the potential to progress to a severe
      debilitating state. Treatment with biological agents is highly efficient,
      improving both short-term outcomes and long-term prognosis. Nonetheless, up to
      60% of patients receiving biological therapy will exhibit nonresponse at some
      point. The optimal management of such patients is not clearly defined. Besides
      traditional anti-TNF agents (infliximab, adalimumab, and certolizumab),
      alternative biological therapies (natalizumab, vedolizumab, and ustekinumab) are
      currently available for the treatment of CD. Our aim was to analyze all available
      evidence regarding efficacy of a second biological in "biological-treatment
      experienced" patients. Methods: A systematic review of the literature was
      conducted using specific criteria for selecting relevant randomized clinical
      trials evaluating response to administration of secondary biological therapy in
      "anti-TNF-experienced" CD patients. Data from these studies was used to perform
      (a) traditional meta-analysis to ascertain the effect of secondary treatment
      versus placebo and (b) network meta-analysis to compare indirectly the efficacy
      of available biological agents. Results: Out of initially 977 studies, only eight
      were included for analysis, providing a total of 1281 treated and 733 placebo
      receiving CD patients. Treatment with a second biological was found to be
      superior to placebo for both induction of remission (OR 2.2, 95% CI 1.7 to 3) and
      response (OR 1.9, 95% CI 1.5 to 2.5), with global rates of 24% and 42%,
      respectively (placebo rate: 11% and 27%, p < 0.0001 for both). Indirect
      comparisons performed with network meta-analysis suggest no specific agent is
      clearly superior to others, with relatively better results observed for
      adalimumab in inducing disease remission. Conclusion: In anti-TNF-experienced CD
      patients, secondary biological administration may be efficient, while no specific
      agent seems to outperform the others. Further research is needed to identify
      optimal management strategies for this challenging subset of patients.

PMID- 30116267
TI  - Ingesting Self-Grown Produce and Seropositivity for Hepatitis E in the United
      States.
AB  - Background: Hepatitis E virus (HEV) is a major cause of hepatitis in developing
      and industrialized countries worldwide. The modes of HEV transmission in
      industrialized countries, including the United States, remain largely unknown.
      This study is aimed at evaluating the association between HEV seropositivity and
      consumption of self-grown foods in the United States. Methods: Cross-sectional
      data was extracted from the 2009-2012 National Health and Nutrition Examination
      Survey (NHANES). Data from the dietary interview and the serum HEV IgG and IgM
      enzyme immunoassay test results were linked and examined. Univariate and
      multivariable logistic regression models were used to evaluate the significance
      and effect size of an association between self-grown food consumption and
      hepatitis E seropositivity. Results: The estimated HEV seroprevalence in the
      civilian, noninstitutionalized US population was 6.6% in 2009-2012, which
      corresponds to an estimated hepatitis E national seroprevalence of 17,196,457
      people. Overall, 10.9% of participants who ingested self-grown foods had positive
      HEV antibodies versus 6.1% of participants who did not consume self-grown foods
      (P < 0.001; odds ratio (OR) 1.87; 95% CI 1.41-2.48). In the age-stratified
      multivariable analysis, the correlation between ingesting self-grown foods and
      HEV seropositivity was significant for participants 40-59 years old, but not
      overall, or for those < 40 years or >=60 years. Conclusions: Ingesting self-grown
      food, or simply the process of gardening/farming, may be a source of zoonotic HEV
      transmission.

PMID- 30116268
TI  - Caesarean Section Rates and Activity-Based Funding in Northern Norway: A Model
      Based Study Using the World Health Organization's Recommendation.
AB  - Objective: Caesarean section (CS) rates vary significantly worldwide. The World
      Health Organization (WHO) has recommended a maximum CS rate of 15%. Norwegian
      hospitals are paid per CS (activity-based funding), employing the diagnosis
      related group (DRG) system. We aimed to document how financial incentives can be
      affected by reduced CS rates, according to the WHO's recommendation. Methods: We
      employed a model-based analysis and included the 2016 data from the Norwegian
      Patient Registry (NPR) and the Medical Birth Registry of Norway (MBRN). The
      vaginal birth rate and CS rates of each hospital trust in Northern Norway were
      analyzed. Results: There were 4,860 deliveries and a 17.5% CS rate (range 13.9
      20.3%). The total funding of the deliveries was ?16,351,335 (CS: ?6,389,323;
      vaginal births: ?9,962,012). The CS rate varied significantly and was lower in
      the southern region (P < 0.002). Consequently, the introduction of a cutoff at a
      15% CS rate would gain the two southern hospital trusts by a budget increase of
      0.2%. The two northern ones would experience 6.4% less resources. A total of
      ?644,655 could be allocated to further quality and safety initiatives in
      obstetrics. Conclusion: The economic consequences of the model-based financial
      incentive were low, but probably sufficient to get the necessary attention and
      influence on the CS rate. Recommendations: A financial incentive for the
      reduction of CS rates should be tested as a supplement to other instruments.

PMID- 30116269
TI  - Female Genital Mutilation: Health Consequences and Complications-A Short
      Literature Review.
AB  - Female genital mutilation (FGM) is a procedure performed on women in developing
      countries and is underreported; it involves cutting or altering the female
      genitalia. The health consequences of FGM include bacterial and viral infections,
      obstetrical complications, and psychological problems. In this study, we report
      FGM societal importance, ramifications, classifications, cultural significance,
      prevalence, complications, implications, and treatment. Although efforts have
      been made to eradicate FGM, the dynamics that perpetuate the practice have
      societal roots. Intervention methods to promote change from within the community
      are necessary for successful eradication of the practice. For prevention, further
      studies are needed to develop programs that raise awareness.

PMID- 30116270
TI  - Effects of Single-Nucleotide Polymorphisms in Cytokine, Toll-Like Receptor, and
      Progesterone Receptor Genes on Risk of Miscarriage.
AB  - Spontaneous abortion is a complex, multifactorial pathology, where various
      genetic, neural, endocrine, and immunological factors are involved. Cytokines,
      Toll-like receptors, and progesterone receptors play critical roles in embryonic
      implantation and development. A delicate, stage-specific equilibrium of these
      proteins is required for successful pregnancy outcome. However, genetic variation
      from one individual to another results in variation in levels of Th1/Th2
      cytokines, strength of identification of infectious agents by Toll-like
      receptors, and quality of progesterone recognition. Thus, a complex study
      encompassing effects of major SNPs of cytokine, TLR, and PGR genes on the risk of
      miscarriage is needed. In this study, we investigated SNPs of 9 genes (TLR2
      G753A, TLR4 C399T, TLR9 G2848A, TGF-beta1 C509T, PGR PROGINS, IL-6 G174C, IL-8
      C781T, IL-10 C592A, and TNFalpha G308A) in 106 women, whose pregnancy ended in
      miscarriage, and 74 women, who delivered in term without any pregnancy
      complication. All participants are from Ukrainian population. As a result, TLR9
      and IL-10 SNPs have been found to play critical roles in the development of
      spontaneous abortion. TLR2, TLR4, IL-6, IL-8, and PGR SNPs were identified as
      secondary factors that can also affect the risk of miscarriage. There was no
      association found between TGF-beta1 and TNFalpha polymorphisms and miscarriage.

PMID- 30116271
TI  - Management of Menstrual Disorder in Adolescent Girls with Intellectual
      Disabilities: A Blessing or a Curse?
AB  - Objective: This study aims to describe the menstrual pattern and menstrual care
      of girls with intellectual disabilities and to evaluate the impact of
      menstruation and awareness of parents/guardians on girls with intellectual
      disabilities. Methodology: Parents/guardians of girls aged 9-17 years with known
      intellectual disabilities who attended a scheduled public forum and Paediatrics
      and Adolescent Gynaecology Clinic (PAC) were recruited in a questionnaire-based
      study. Results: A total of 123 parents/guardians with a mean age of 41.83 +/-
      5.45 years completed the questionnaire. The mean age of girls with intellectual
      disabilities was 12.28 +/- 2.78 years, and the mean menarcheal age was 11.12 +/-
      1.76 years. Only 53 (43.1%) parents/guardians were aware of availability of
      menstrual suppression. Parents/guardians with lower family income (OR = 0.00; 95%
      CI = 0.00-0.20), unable to manage menses (OR = 0.03; 95% CI = 0.00-0.61), and
      moderate severity of menses (OR = 0.01; 95% CI = 0.00-1.21), were associated with
      seeking medical help on menstrual suppression. The factors associated with
      parents/guardians requesting for sterilization were lower family income (OR =
      0.02; 95% CI = 0.00-0.36) and concern about sexual abuse (OR = 0.25; 95% CI =
      0.06-0.39). Conclusion: Menstrual pattern in girls with intellectual disabilities
      is similar to those without disabilities. Parents/guardians' knowledge and
      awareness on menstrual suppression were still lacking.

PMID- 30116272
TI  - The notch pathway promotes NF-kappaB activation through Asb2 in T cell acute
      lymphoblastic leukemia cells.
AB  - Background: Oncogenic Notch1 is known to activate the NF-kappaB pathway in T cell
      acute lymphoblastic leukemia (T-ALL) and to up-regulate the transcription of
      Asb2alpha, a specificity factor for an E3 ubiquitin ligase complex that plays an
      important role in hematopoietic differentiation. Therefore, we hypothesize that
      Notch1 might regulate the NF-kappaB pathway through Asb2alpha. Methods: The study
      involved down-regulation of Notch1 in T-ALL cell lines (CCRF-CEM cells and MOLT-4
      cells) through treatment with gamma-secretase inhibitor (GSI) as well as the
      modulation of Asb2 in CCRF-CEM cells and MOLT-4 cells through transduction with
      lentivirus carrying Asb2 or Asb2-shRNA. Experiments using real-time PCR, western
      blot and co-immunoprecipitation were performed to evaluate the expression levels
      of related genes. Cell proliferation and apoptosis were measured while the
      expression of Asb2 was enhanced or inhibited. Results: Here, we demonstrated for
      the first time that Notch1 can activate the transcription of Asb2alpha, which
      then stimulates activation of NF-kappaB in T-ALL cells. Asb2alpha exerts its
      effects by inducing degradation and dissociation of IkappaBalpha from NF-kappaB
      in T-ALL cells. Moreover, specific suppression of Asb2alpha expression can
      promote apoptosis and inhibit proliferation of T-ALL cells. Conclusion: Notch1
      modulates the NF-kappaB pathway through Asb2alpha, indicating that Asb2alpha
      inhibition is a promising option for targeted therapy against T-ALL.

PMID- 30116274
TI  - The Significance of Serum Interleukin-8 in Acute Exacerbations of Chronic
      Obstructive Pulmonary Disease.
AB  - Backgrounds: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD)
      is closely related to disease mortality. Systemic inflammation is considered to
      be involved in the pathogenesis of AECOPD. The current study aimed to investigate
      the clinical significance of the classic chemokine interleukin (IL)-8 in serum
      during AECOPD. Materials and Methods: In this current cross sectional,
      observational study, 50 patients with AECOPD, 25 patients with stable COPD and 25
      healthy nonsmokers as the control group were selected. Clinical characteristics
      and spirometry data were collected. All patients were classified as grade 1-4
      based on forced expiratory volume in 1 second (FEV1) after bronchodilation
      according to the GOLD severity classification and were divided into frequent
      exacerbation (FE) group (>=2 times/year) and non-frequent exacerbation (NFE)
      group (<1 time/year) according to acute exacerbation (AE) times in the previous
      12 months before the visit. The serum IL-8, IL-6, tumor necrosis factor (TNF)
      alpha, and superoxide dismutase levels were measured by the enzyme-linked
      immunosorbent assay technique. Results: Serum IL-8 levels increased sequentially
      from controls [9.45 pg/mL (ranged: 6.85-38.4)], to stable [51.60 pg/mL (ranged:
      22.4-131.1)], and exacerbation stage [129 pg/mL (ranged: 57.7-374)]. The level of
      serum IL-8 was significant higher in patients with FE than that of patients with
      NFE (209.0 pg/mL (ranged: 115-472) vs 65.6 pg/mL (ranged: 11.2-149.3), P=0.008).
      A receiver operating characteristics curve (ROC) generated to evaluate IL-8, IL
      6, and TNF-alpha levels to discriminate between patients with and without
      exacerbation showed that the total area under the curve (AUC) was 0.71 (95%
      confidence interval (CI): 0.5764-0.8381; P=0.003), 0.54 (95%CI: 0.4048-0.6943;
      P=0.54), and 0.52 (95%CI: 0.3912-0.6656; P= 0.7). Conclusion: Serum IL-8 is a
      sensitive, easy-to-measure, and inexpensive biomarker to give an indication of
      the course of COPD during exacerbation, and is a target to be explored further as
      a predictor to distinguish the patients prone to exacerbation.

PMID- 30116275
TI  - Analgesic Effects of Ketamine, Magnesium Sulfate, and Sodium-Thiopental on
      Propofol Injection Pain: A Single-Blind Randomized Clinical Trial.
AB  - Background: Propofol is one of the most frequently used medications for inducing
      and maintaining anesthesia. However, propofol injection causes pain and
      discomfort in more than 70% of patients. This study was performed to determine
      the comparative effects of ketamine, sodium-thiopental, and magnesium sulfate on
      reducing pain at the onset of anesthesia induced by propofol injection. Materials
      and Methods: This single-blind randomized clinical trial was conducted on a
      population of patients, requiring nonemergency surgeries. The sample size was
      determined as 25 patients per group. The eligible samples were randomly divided
      into three groups. An 18-gauge intravenous catheter was inserted in the dorsum of
      the hand for all patients. Three groups received 0.5 ml/kg of ketamine, 30 mg/kg
      of magnesium sulfate, and 0.5 ml/kg of sodium-thiopental, respectively. Next, 2.5
      mg/kg of propofol 2% was administered at a rate of 1 ml/s. The verbal rating
      scale (VRS) was applied to assess the severity of pain during injection. Results:
      According to the results, the prevalence of pain was 36% in the magnesium sulfate
      group, 16% in the sodium-thiopental group, and 4% in the ketamine group. The
      ordinal logistic regression test showed that patients from the ketamine group
      experienced less pain, compared to the magnesium sulfate group (OR, 0.045; P=
      0.008). However, no significant difference was observed between the ketamine and
      sodium-thiopental groups (OR, 0.253; P= 0.283). Conclusion: Ketamine and sodium
      thiopental can be effective medications in reducing pain caused by propofol
      injection. According to the results, magnesium sulfate is not recommended for
      reducing pain due to propofol injection.

PMID- 30116273
TI  - Imbalanced Expression of Th2 and Treg Cell-related Parameters in Peripheral Blood
      Mononuclear Cells in Patients with Allergic Asthma.
AB  - Background: The imbalance between Th2 and Treg cells plays fundamental role in
      the pathogenesis of allergic asthma. The current study aimed at assessing the
      expression of some Th2 and Treg cell-related parameters in patients with allergic
      asthma. Material and Methods: The serum and peripheral blood mononuclear cell
      (PBMC) samples were collected from 30 patients with asthma and 36 healthy
      subjects. The serum levels of transforming growth factor (TGF)-beta, interleukin
      (IL)-4, as well as the expression levels of GATA3 and FOXP3 genes in PBMCs were
      determined by the enzyme-linked immunosorbent assay (ELISA) and real-time
      polymerase chain reaction (PCR), respectively. The PBMCs were cultured for 48
      hours with/without phytohemagglutinin (PHA) stimulation. The TGF-beta and IL-4
      levels in supernatants were also determined. Results: The serum levels of IL-4,
      the expression level of GATA3, and GATA3/FOXP3 ratio in patients with asthma were
      significantly higher than healthy subjects (P <0.002, P <0.001, and P <0.004,
      respectively). The FOXP3 expression did no differ between the two groups. The
      serum level of TGF-beta as well as its secretion profile in non-stimulated and
      stimulated PBMCs isolated from patients with asthma were significantly higher
      than those of the controls (P <0.03, P <0.001, and P <0.001, respectively). The
      serum TGF-beta levels in severe asthma were significantly higher than moderate
      asthma; whereas the TGF-beta secretion by PHA-stimulated PBMCs isolated from
      moderate asthma was higher than that of severe pattern of the disease (P <0.001
      and P <0.05, respectively). The GTAT3/FOXP3 expression ratio in moderate asthma
      was significantly higher than severe form (P <0.04). Conclusion: The results
      confirmed a Th2 cell-biased pattern and possible contribution of TGF-beta in
      allergic asthma. TGF-beta may have different expression patterns in moderate and
      severe asthma and the two forms of the disease may have differences in some main
      immunological parameters.

PMID- 30116276
TI  - Effects of Cold Application on Chest Tube Removal Pain in Heart Surgery Patients.
AB  - Background: Chest tube removal is considered a painful technique, which may not
      respond well to palliative therapies. There are no standard procedures or
      guidelines to manage the pain associated with chest tube removal. This study
      aimed to examine the effects of cold application on pain reduction during and
      after chest tube removal. Materials and Methods: This randomized controlled trial
      was conducted on 90 hospitalized patients, undergoing heart bypass surgery at the
      intensive care units where at least a pleural chest tube was inserted. The
      patients were randomly divided into two groups (45 samples per group). In the
      cold application group, an ice bag was placed at the designated point for 20
      minutes before chest tube removal, while only routine interventions were applied
      for chest tube removal in the control group. Pain severity was measured in the
      groups before, during, and 15 minutes after chest tube removal, using the visual
      analogue scale. Repeated measures ANOVA test was applied for data analysis.
      Results: There was no significant difference in the baseline pain score between
      the groups (P= 0.18). However, there was a significant difference in terms of
      pain severity score between the cold application (3.58+/-1.09) and control
      (4.73+/-0.86) groups during chest tube removal (P< 0.001). On the other hand,
      there was no significant difference between the groups regarding the score of
      pain severity at 15 minutes after chest tube removal (P= 0.38). Conclusion: Cold
      application, as a nonpharmacological intervention, may contribute to the
      alleviation of cryotherapy-related pain.

PMID- 30116277
TI  - Pulmonary Function and Hospital Admission in Patients with Cystic Fibrosis Based
      on Household Second-Hand Smoking.
AB  - Background: Smoking is a known predisposing factor to exacerbations in CF
      patients. But the effects of second-hand tobacco smoking are not yet clear.
      Hence, this study determined the clinical and spirometric presentations and
      urinary cotinine levels among cystic fibrosis patients over seven years of age in
      relation to their parent's smoking history. Materials and Methods: In this cross
      sectional comparative study, 58 consecutive cystic fibrosis patients older than
      seven years of age were enrolled. These patients were divided into two equal
      groups: those with second-hand tobacco smoking and those without. Pulmonary
      function tests and hospital admission rates were compared across the groups.
      Results: The mean hospital admission times were 5.1+/-2.4 in the group with
      passive smoking, and 2.6+/-1.3 times in the group without (P<0.001). The cotinine
      level was reversely correlated to time interval passed from previous admissions
      (P=0.001, r=-0.432) in passive smokers and (P=0.021, r=0.314) in non-passive
      smokers. In the analysis of FEV1 with urine, there was a significant but negative
      relation between FEV1 and cotinine (P= 0.002). Besides, in the analysis of FE 25
      75 and urine cotinine, there was also a significant and negative relationship
      (P=0.001). Conclusion: From our findings, we conclude that pulmonary function
      tests and hospital admission rate in patients with cystic fibrosis are associated
      with urinary cotinine level and household second-hand tobacco smoking.

PMID- 30116278
TI  - Assessment of Pulmonary Function Parameters, Signs, and Symptoms in the Employee
      of a Dairy Products Company in Tehran, Iran.
AB  - Background: Workers in dairy products companies are exposed to different
      respiratory hazards. The current study aimed at investigating and comparing the
      prevalence of pulmonary function parameters, signs, and symptoms in the exposed
      workers and office staff. Materials and Methods: The current cross sectional
      study was conducted in 2015 on 864 employees working in a dairy products company
      in Tehran, Iran. The subjects included 646 employees exposed to respiratory
      hazards at the production line and the other group consisted of 218 staff not
      exposed to respiratory hazards in the production line as the unexposed group.
      Demographic characteristics and the presence of respiratory symptoms and signs
      were gathered using a checklist. Spirometric indices including FEV1, forced
      volume vital capacity (FVC), and FEV1/FVC were measured for the study
      participants. Results: Although exposure to the respiratory hazards among
      participants of the exposed group was lower than permitted limits, the frequency
      of respiratory signs and symptoms were significantly higher than those of the
      unexposed staff. In the current study, mean percentage of FVC, FEV1/FVC, and FEV1
      were significantly less than the predicted amount in the exposed group than in
      the unexposed group. Conclusion: Although the frequency of respiratory signs and
      symptoms was lower than those of other similar studies, abnormal spirometric
      patterns were common; hence, it can be pointed out that even in the work
      environments, such as dairy products industry with below the permissible exposure
      limit of respiratory risks, multiple spirometric disorders can be observed. In
      other words, the absence of respiratory signs and symptoms are insufficient and
      application of different pulmonary function tests, such as spirometry, seem
      essential for assessment.

PMID- 30116279
TI  - Effect of Family Empowerment on Asthma Control in School-Age Children.
AB  - Background: Recent surveys have showed that asthma control still remains
      suboptimal. Family members have an extensive impact on the level of asthma
      control in school-age children. Family empowerment has a positive impact on the
      quality of life of school-age children with asthma. This study aimed to determine
      the efficacy of family empowerment on asthma control in school-age children.
      Materials and Methods: Forty-five children with asthma (6-12 years) and their
      parents were enrolled in a pediatric asthma clinic during their follow-up visits.
      The family empowerment program consisted of self-directed educational material,
      lectures (a nurse-focused format), group interaction (a learner-focused format),
      group discussions, and demonstration of educational films. The primary outcome
      was change in asthma control measured by the C-ACT questionnaire. Results: In
      this study, 45 patients were enrolled and randomly divided into two groups:
      intervention (n=23) and control (n=22). Demographic variables including age and
      sex were not significantly different between the two groups. There were no
      significant differences in pre-test asthma control scores between the
      intervention and control groups at pre-test (p=0.82). However, there was a
      significant difference in asthma control scores between the intervention and
      control groups at post-test (p<0.001). In the intervention group, in which
      children experienced family empowerment, asthma control scores were significantly
      higher at post-test compared to pre-test (p<0.001). Conclusion: Family
      empowerment significantly improved asthma control in school-age pediatric
      patients. This program could be proposed for proper asthma control and
      complication-reducing management of the disease. This program is recommended more
      broadly for other age groups.

PMID- 30116280
TI  - Successful Treatment of Massive Pulmonary Thromboembolism with Reteplase: Case
      Series.
AB  - Massive pulmonary thromboembolism (PTE) has an increased risk of mortality.
      Thrombolytic therapy is the accepted treatment. Reteplase, a variant of tissue
      plasminogen activator, has been used in acute myocardial infarction with
      acceptable safety and efficacy, but studies in massive PTE are rare. In this
      study we report five cases of successful treatment of massive PTE with reteplase.

PMID- 30116281
TI  - Anesthesia Management of Vitrectomy in a Patient with Sturge-Weber Syndrome.
AB  - Sturge-Weber syndrome (SWS) is a neurocutaneous disorder, characterized by
      leptomeningeal angiomas involving the oral cavity, trachea, larynx, and face.
      Herein, we present a case of vitrectomy in a seven-year-old boy with SWS. The
      patient showed hemangioma on the left side of his face, as well as mental
      retardation and epilepsy. Preoperative examination revealed no apparent
      hemangioma in the oral cavity, pharynx, larynx, or trachea. However, he was
      predicted to have difficult airway intubation, as the oral cavity was smaller
      than the normal size. The minimum Mallampati score was 3-4 due to macroglossia.
      First, we applied awake intubation, but he failed to follow the commands. We
      proceeded to general anesthesia with propofol and did not use any muscle
      relaxants to maintain spontaneous breathing. A laryngeal mask airway was inserted
      to minimize any harm to possible oral angiomas. The patient was hemodynamically
      stable and extubated without any complications, such as bleeding or respiratory
      problems.

PMID- 30116282
TI  - A Rare Report of Lung Metastasis of the Common Non-Melanotic Skin Cancer.
AB  - Basal cell carcinoma is a common non-melanotic skin cancer with a prevalence of
      74.5%-82.6% in the Iranian population. BCC rarely metastasizes. However,
      metastasis can cause significant morbidity. The prevalence of metastatic basal
      cell carcinoma varies between 0.0028% and 0.55% of all cases. We describe a case
      of lung metastasis of basal cell carcinoma of the scalp.

PMID- 30116284
TI  - Sacubitril/valsartan: evaluation of safety and efficacy as an antihypertensive
      treatment.
AB  - Hypertension (HTN) is a common disease state associated with extensive morbidity
      and mortality worldwide. It is often difficult for patients with HTN to achieve
      and maintain a goal blood pressure (BP), despite there being many effective
      treatment options available. Sacubitril/valsartan is a first-in-class angiotensin
      receptor neprilysin inhibitor (ARNI) that has garnered approval by the US Food
      and Drug Administration and the European Medicines Agency as a first-line
      treatment for heart failure with reduced ejection fraction. During clinical
      trials for heart failure as well as in independent trials for HTN,
      sacubitril/valsartan has demonstrated safety and efficacy when it comes to BP
      lowering, making it a promising antihypertensive agent. Most trials of
      sacubitril/valsartan were 8 to 12 weeks in length and demonstrated a clinically
      relevant BP lowering that was frequently more significant than its comparators.
      While more data are needed to confirm its role as an antihypertensive agent, the
      data available are promising and it is anticipated that sacubitril/valsartan will
      gain an indication of HTN.

PMID- 30116283
TI  - Advances in the use of PARP inhibitor therapy for breast cancer.
AB  - Poly-ADP-ribose polymerase 1 (PARP-1) and PARP-2 are DNA damage sensors that are
      most active during S-phase of the cell cycle and that have wider-reaching roles
      in DNA repair than originally described. BRCA1 and BRCA2 (Breast Cancer) proteins
      are involved in homologous recombination repair (HRR), which requires a
      homologous chromosome or sister chromatid as a template to faithfully repair DNA
      double-strand breaks. The small-molecule NAD+ mimetics, olaparib, niraparib,
      rucaparib, veliparib, and talazoparib, inhibit the catalytic activity of PARP-1
      and PARP-2 and are currently being studied in later-stage clinical trials. PARP
      inhibitor clinical trials have predominantly focused on patients with breast and
      ovarian cancer with deleterious germline BRCA1 and BRCA2 mutations (gBRCA1/2+)
      but are now expanding to include cancers with known, suspected, or more-likely
      than-not defects in homologous recombination repair. In ovarian cancer, this
      group also includes women whose cancers are responsive to platinum therapy.
      Olaparib was FDA-approved in January 2018 for the treatment of gBRCA1/2+
      metastatic breast cancers. gBRCA1+ predisposes women to develop triple-negative
      breast cancers, while women with gBRCA2+ tend to develop hormone-receptor
      positive, human epidermal growth factor receptor 2 negative breast cancers.
      Although PARP inhibitor monotherapy strategies seem most effective in cancers
      with homologous recombination repair defects, combination strategies may allow
      expansion into a wider range of cancers. By interfering with DNA repair, PARP
      inhibitors essentially sensitize cells to DNA-damaging chemotherapies and
      radiation therapy. Certainly, one could also consider expanding the utility of
      PARP inhibitors beyond gBRCA1/2+ cancers by causing DNA damage with cytotoxic
      agents in the presence of a DNA repair inhibitor. Unfortunately, in numerous
      phase I clinical trials utilizing a combination of cytotoxic chemotherapy at
      standard doses with dose-escalation of PARP inhibitors, there has generally been
      failure to reach monotherapy dosages of PARP inhibitors due to myelosuppressive
      toxicities. Strategies utilizing angiogenesis inhibitors and immune checkpoint
      inhibitors are generally not hindered by additive toxicities, though the utility
      of combining PARP inhibitors with treatments that have not been particularly
      effective in breast cancers somewhat tempers enthusiasm. Finally, there are
      combination strategies that may serve to mitigate resistance to PARP inhibitors,
      namely, upregulation of the intracellular PhosphoInositide-3-kinase, AK thymoma
      (protein kinase B), mechanistic target of rapamycin (PI3K-AKT-mTOR) pathway, or
      perhaps are more simply meant to interfere with a cell growth pathway heavily
      implicated in breast cancers while administering relatively well-tolerated PARP
      inhibitor therapy.

PMID- 30116285
TI  - Clarifying questions about "risk factors": predictors versus explanation.
AB  - Background: In biomedical research much effort is thought to be wasted.
      Recommendations for improvement have largely focused on processes and procedures.
      Here, we additionally suggest less ambiguity concerning the questions addressed.
      Methods: We clarify the distinction between two conflated concepts, prediction
      and explanation, both encompassed by the term "risk factor", and give methods and
      presentation appropriate for each. Results: Risk prediction studies use
      statistical techniques to generate contextually specific data-driven models
      requiring a representative sample that identify people at risk of health
      conditions efficiently (target populations for interventions). Risk prediction
      studies do not necessarily include causes (targets of intervention), but may
      include cheap and easy to measure surrogates or biomarkers of causes. Explanatory
      studies, ideally embedded within an informative model of reality, assess the role
      of causal factors which if targeted for interventions, are likely to improve
      outcomes. Predictive models allow identification of people or populations at
      elevated disease risk enabling targeting of proven interventions acting on causal
      factors. Explanatory models allow identification of causal factors to target
      across populations to prevent disease. Conclusion: Ensuring a clear match of
      question to methods and interpretation will reduce research waste due to
      misinterpretation.

PMID- 30116286
TI  - Metabolomic profiles associated with bone mineral density in US Caucasian women.
AB  - Background: Individuals' peak bone mineral density (BMD) achieved and maintained
      at ages 20-40 years is the most powerful predictor of low bone mass and
      osteoporotic fractures later in life. The aim of this study was to identify
      metabolomic factors associated with peak BMD variation in US Caucasian women.
      Methods: A total of 136 women aged 20-40 years, including 65 subjects with low
      and 71 with high hip BMD, were enrolled. The serum metabolites were assessed
      using a liquid chromatography-mass spectrometry (LC-MS) method. The partial least
      squares discriminant analysis (PLS-DA) method and logistic regression models were
      used, respectively, to examine the associations of metabolomic profiles and
      individual metabolites with BMD. Results: The low and high BMD groups could be
      differentiated by the detected serum metabolites using PLS-DA (Ppermutation =
      0.008). A total of 14 metabolites, including seven amino acids and amino acid
      derivatives, five lipids (including three bile acids), and two organic acids,
      were significantly associated with the risk for low BMD. Most of these
      metabolites are novel in that they have never been linked with BMD in humans
      earlier. The prediction model including the newly identified metabolites
      significantly improved the classification of the groups with low and high BMD.
      The area under the receiver operating characteristic curve without and with
      metabolites were 0.88 (95% CI: 0.83-0.94) and 0.97 (95% CI: 0.94-0.99),
      respectively (P for the difference = 0.0004). Conclusion: Metabolomic profiling
      may improve the risk prediction of osteoporosis among Caucasian women. Our
      findings also suggest the potential importance of the metabolism of amino acids
      and bile acids in bone health.

PMID- 30116288
TI  - Association of Schizoid and Schizotypal Personality disorder with violent crimes
      and homicides in Greek prisons.
AB  - Background: Personality disorders (PDs) have been associated with both violent
      crimes and homicides in many studies. The proportion of PDs among prisoners
      reaches up to 80%. For male prisoners, the most common PD in the literature is
      antisocial PD. The aim of this study was to investigate the association between
      PDs and violent crimes/homicides of male prisoners in Greece. Methods: A sample
      of 308 subjects was randomly selected from a population of 1300 male prisoners
      incarcerated in two Greek prisons, one urban and one rural. The presence of PDs
      was assessed using the Mini International Neuropsychiatric Interview (MINI) and
      the Personality Diagnostic Questionnaire-4 (PDQ-4). Using logistic regression
      models PD types and PD "Clusters" (independent variables) were associated with
      "violent/non-violent crimes" and "homicides/non homicides" (dependent variables).
      Results: "Cluster A" PDs (Paranoid, Schizoid, and Schizotypal) were diagnosed in
      16.2%, "Cluster B" (Antisocial, Borderline, Histrionic, Narcissistic) in 66.9%
      and "Cluster C" (Obsessive-Compulsive, Dependent, Avoidant) in 2.9% of the
      studied population. Violent crimes and homicides were found significantly
      associated with "Cluster A" PDs (p = 0.022, p = 0.020). The odds ratio of
      committing violent crimes was 2.86 times higher for patients with "Cluster A" PDs
      than the ones without PDs. In addition, the odds ratio of committing homicides
      was 4.25 times higher for patients with "Cluster A" PDs. In separate analyses,
      the commitment of violent crimes as well as homicides, was significantly
      associated with Schizoid (p = 0.043, p = 0.020) and Schizotypal PD (p = 0.017, p
      = 0.030). Conclusions: The majority of prisoners was found to suffer from a PD,
      mainly the Antisocial "Cluster B", but the commitment of violent crimes and
      homicides was significantly associated only with "Cluster A" PDs and specifically
      with Schizoid and Schizotypal PD.

PMID- 30116290
TI  - Prevalence of exclusive breastfeeding and barriers for its continuation up to six
      months in Kandy district, Sri Lanka.
AB  - Background: Since 2005, the national policy on breastfeeding in Sri Lanka is
      exclusive breastfeeding up to 6 months, as recommended by World Health
      Organization. The objective of this study was to assess the prevalence of
      exclusive breastfeeding and barriers for its' continuation up to 6 months, in
      Kandy District, Sri Lanka. Methods: A clinic based cross-sectional study was
      conducted from August to November 2016, in six randomly selected Medical Officer
      of Health areas in the Kandy District. The sample was selected proportionate to
      the population of each Medical Officer of Health area and 354 mothers with
      infants aged 6 months, attending the child welfare clinics were recruited. Data
      were collected by an interviewer administered questionnaire using mother recall
      data since birth. A focus group discussion was conducted on 21 mothers who
      discontinued exclusive breastfeeding early. The infant taking only breast milk
      and no additional food, water, or other fluids with the exception of medicines
      and vitamins or mineral drops for the first 6 months was used as the definition
      of exclusive breastfeeding. Results: The prevalence of exclusive breastfeeding
      for 6 months was 50.8% (180/354) while the median duration was 6 months. Mother
      being employed (AOR 3.01; 95% CI 1.45, 6.29), mother's poor knowledge on what she
      meant by exclusive breastfeeding (AOR 3.75; 95% CI 2.14, 6.54) and mother's poor
      attitudes towards exclusive breastfeeding (AOR 2.98; 95% CI 1.76, 5.03) were
      independently associated with early cessation of exclusive breastfeeding.
      Unsupported environment in public places was not significantly associated with
      early cessation of exclusive breastfeeding. Focus group discussion revealed
      controversial health messages on exclusive breastfeeding delivered at different
      points of healthcare delivery, cultural practices which discouraged exclusive
      breastfeeding and difficulties in obtaining maternity leave as barriers for
      exclusive breastfeeding. Conclusions: The prevalence of exclusive breastfeeding
      up to 6 months was not satisfactory and there were barriers identified in
      healthcare system, family and work places towards exclusive breastfeeding. For
      further improvement in the prevalence of exclusive breastfeeding these issues
      need to be addressed and necessary changes in legislation implemented.

PMID- 30116287
TI  - Dietary vitamin D3 supplementation protects laying hens against
      lipopolysaccharide-induced immunological stress.
AB  - Background: The effects of vitamin D on the immune function of laying hens are
      not well understood. This study investigated the effects of vitamin D3 (VD3) on
      laying performance and immunological functions in laying hens under Escherichia
      coli lipopolysaccharide (LPS) challenge. Methods: In experiment one, 360 Jinghong
      1 strain layers (32 weeks) were randomly divided into four groups with six
      replicates per group and 15 hens per replicate. Hens were fed a basal diet
      supplemented with different levels of VD3 (0; 500; 1500; or 3000 IU VD3/kg of
      diet) for 10 weeks to determine laying performance, egg quality, and other
      parameters. In experiment two, 24 Jinghong laying hens (32 weeks) were fed basal
      diets with either 0 or 3000 IU VD3/kg of diet. After 10 weeks of feeding, six
      hens from each treatment were injected intravenously with 8 mg/kg of body weight
      of either LPS or saline. Blood and spleen samples were obtained for immune
      parameter analysis 4 h after injection. Results: VD3 deficiency reduced egg
      production and egg quality; in addition, feed intake and feed-to-egg ratio
      increased. No significant differences were observed in these parameters except
      eggshell strength between dietary VD3 supplemental levels at 500; 1500; and 3000
      IU VD3/kg of diet. VD3 deficiency increased serum hormone (calcitonin,
      parathyroid hormone, estradiol, and progesterone) and cytokine (IL-6, IL-10)
      levels, the ratio of IFN-gamma to IL-4, myeloperoxidase activity and total IgG
      content in the serum, and upregulated the blood CD3+ T cell population. Splenic
      retinoid X receptor (RXR), nuclear factor-kappaB (NF-kappaB), inducible nitric
      oxide synthase (iNOS), and polymeric immunoglobulin receptor (pIgR) gene mRNA
      levels were upregulated in VD3-deficienct hens. VD3 deficiency significantly
      reduced serum Follicle stimulating hormone (FSH) and Luteinizing hormone (LH)
      concentrations and the number of CD4+CD25+ T cells in the blood. These changes
      were completely normalized by VD3 sufficiency. LPS reduced serum LH
      concentration, splenic lysozyme, and pIgR gene mRNA levels. LPS induced an
      increase in total serum IgM levels and the percentage of CD8+ T cells in the
      blood. The changes were completely reversed by VD3 addition. Conclusion: VD3
      supplementation could protect laying hens not only from VD3 deficiency but also
      from immunological stress.

PMID- 30116289
TI  - Mutagenic and DNA repair activity in traffic policemen: a case-crossover study.
AB  - Background: Emissions from vehicles are composed of heterogeneous mixtures of
      hazardous substances; several pollutants such as Polycyclic Aromatic Hydrocarbons
      (PAHs) are amongst the most dangerous substances detected in urban monitoring. A
      cohort of traffic policemen usually occupationally exposed to PAHs present in the
      urban environment were examined in order to assess the mutagenicity and DNA
      capacity repair. Methods: Seventy-two urban traffic policemen working in
      Catania's metropolitan area were enrolled in the study. Two spot urine samples
      were collected from each subject during the whole working cycle as follows:
      sample 1 (S1), pre-shift on day 1; sample 2 (S2) post-shift on day 6. 1
      hydroxypyrene (1-OHP) was measured to serve as an indirect exposure indicator.
      Urinary mutagenic activity was assessed through the plate incorporation pre
      incubation technique with S9, using YG1024 Salmonella typhimurium strain over
      sensitive to PAH metabolite. Concentrations of urinary 8-oxodG were measured
      using liquid chromatography tandem mass spectrometry. Results: As regards the
      exposure to PAHs, results highlighted a statistically significant difference (p <
      0.001) between pre-shift on day 1 and post-shift on day 6 levels. Mutagenic
      activity was detected in 38 (66%) workers on S1 and in 47 (81%) on S2. Also 8
      oxodG analysis showed a statistically significant difference between S1 and S2
      sampling. Conclusions: This study demonstrated that occupational exposure to
      pollutants from traffic emission, assessed via 1-OHP measurements in urine, may
      lead to DNA repair and mutagenic activity, in line with other studies.

PMID- 30116291
TI  - Dehiscence method: a seed-saving, quick and simple viability assessment in rice.
AB  - Background: Seed viability monitoring is very important in ex situ germplasm
      preservation to detect germplasm deterioration. This requires seed-, time- and
      labor- saving methods with high precision to assess seed germination as
      viability. Although the current non-invasive, rapid, sensing methods (NRSs) are
      time- and labor-saving, they lack the precision and simplicity which are the
      virtues of traditional germination. Moreover, they consume a considerable amount
      of seeds to adjust sensed signals to germination percentage, which disregards the
      seed-saving objective. This becomes particularly severe for rare or endangered
      species whose seeds are already scarce. Here we propose a new method that is
      precise, low-invasive, simple, and quick, which involves analyzing the pattern of
      dehiscence (seed coat rupture), followed by embryonic protrusion. Results:
      Dehiscence proved simple to identify. After the trial of 20 treatments from 3
      rice varieties, we recognized that dehiscence percentage at the 48th hour of
      germination (D(48)) correlates significantly with germination rate for tested
      seed lots. In addition, we found that the final germination percentage
      corresponded to D(48) plus 5. More than 70% of the seeds survived post-dehiscence
      desiccation for storage. Hydrogen peroxide (1 mM) as the solution for imbibition
      could further improve the survival. The method also worked quicker than
      tetrazolium which is honored as a fast, traditional method, in detecting less
      vigorous but viable seeds. Conclusion: We demonstrated the comprehensive virtues
      of dehiscence method in assessing rice seed: it is more precise and easier to use
      than NRSs and is faster and more seed-saving than traditional methods. We
      anticipate modifications including artificial intelligence to extend our method
      to increasingly diverse circumstances and species.

PMID- 30116292
TI  - Facilitating people living with severe and persistent mental illness to
      transition from prison to community: a qualitative exploration of staff
      experiences.
AB  - Background: Transition from prison to community is a challenging time for all
      people who have been incarcerated. It is particularly challenging for those also
      living with serious and persistent mental illness. This study explored staff
      experiences and perspectives of what helped and hindered them in their work to
      support that transition. Methods: Semi-structured interviews were conducted with
      12 mental health staff working across three service sectors directly engaged in
      the process of supporting people with mental illness transitioning from prison to
      community; the forensic mental health provider Justice Health, Community Mental
      Health and a non-government delivered community-based service called Partners in
      Recovery. Data were analysed using constant comparative analysis. Results: Five
      main themes were identified through the analysis. All five themes were key
      practices that, when occurring, supported staff to work in a way that they felt
      would maximise positive outcomes for people transitioning from prison to
      community. These included: housing secured before release; clearly defined and
      effective communication pathways; shared understanding of systems and roles; in
      reach and continuity of contact, and consumers' pre-release preparation and
      knowledge. All staff participants described barriers to good transition to
      community outcomes when some or all of these practices could not, or did not,
      occur. Conclusions: Staff experiences highlight the complexity but importance of
      getting multi-sectorial partnerships and practices right for good prison to
      community transitions for people living with serious and persistent mental
      illness. Currently fragmented and disparate systems and practices need to align
      and clear expectations and understandings need to be shared across the whole.
      These changes, along with prioritised housing are likely to lead to better long
      term outcomes for people.

PMID- 30116293
TI  - Design on the Bowden Cable-Driven Upper Limb Soft Exoskeleton.
AB  - To assist hemiplegic patients with the activities of daily life, many upper limb
      soft exoskeletons have been developed. In this paper, we propose the structure of
      upper limb soft exoskeleton for rehabilitation training based on human
      biomechanics. The soft driving structure based on Bowden cable is devised. Man
      machine interaction force must be considered because it can damage on the joint
      and lead to arm discomfort. We focus on structural optimization to minimize man
      machine interaction force. Human arm model is established to perform motion
      simulation in ADAMS. To summarize optimality conditions, the movements of elbow
      are simulated in ADAMS when the number and location of force bearing points are
      changed. This paper describes the movement of the shoulder skeletal system
      through a mathematical model based on the Bowden cable transmission and utilizes
      man-machine contact force sensor to detect human interaction forces for analysis
      of experimental data. The experimental results show that man-machine interaction
      force can be reduced when the number of bearing force points is increased and
      bearing force point is away from the elbow.

PMID- 30116294
TI  - Numerical Low-Back Booster Analysis on a 6-Year-Old Infant during a Frontal Crash
      Test.
AB  - This work studies descriptively the Head Injury Criterion (HIC) and Chest
      Severity Index (CSI), with a finite element model of the Hybrid III dummy type,
      for six-year-old subjects in a frontal vehicular collision, using the low-back
      booster (LBB) passive safety system. The vehicle seats and the passive safety
      systems were modelled in CAD (computer aided design) software. Then, the elements
      were analysed by the finite element method (FEM) in LS-DYNA(r) software. The
      boundary conditions were established for each study, according to the regulations
      established by the Federal Motor Vehicle Safety Standard (FMVSS), following the
      FMVSS 213 standard. The numerical simulations were performed during an interval
      of 120 ms and recording results every 1 ms. In order to analyse the efficiency of
      the system, the restraint performance of the LBB system is compared with the
      restraint configuration of the vehicle safety belt (VSB) only. The obtained
      injury criteria with the LBB system shows its ability to protect children in a
      frontal collision. The analyses allow obtaining the deceleration values to which
      the dummy head and chest was subjected. Of the studies herein performed, Study I:
      VSB obtained a HIC36 of 730.4 and CSI of 315.5, while Study II: LBB obtained a
      HIC36 of 554.3 and CSI of 281.9. The outcome shows that the restraint efficiency
      of each studied case differs. Used materials, the attachment system of the LBB,
      and the belt restraint system properly placed over the infant trunk are the main
      factors reducing the injury criteria rate.

PMID- 30116295
TI  - The Effects of Leg Length Discrepancy on Stability and Kinematics-Kinetics
      Deviations: A Systematic Review.
AB  - Various studies have examined body posture stability, including postural sway and
      associated biomechanical parameters, to assess the severity effects of leg length
      discrepancy (LLD). However, various viewpoints have been articulated on the
      results of these studies because of certain drawbacks in the comprehensive
      analysis of the effect of variations in LLD magnitude. Therefore, this systematic
      review was performed to help focus on the current findings to help identify which
      biomechanical parameters are most relevant, commonly used, and able to
      distinguish and/or have specific clinical relevance to the effect of variations
      in LLD magnitude during static (standing) and dynamic (walking) conditions.
      Several electronic databases containing studies from the year 1983 to 2016
      (Scopus, ScienceDirect, PubMed, PMC, and ProQuest) were obtained in our
      literature search. The search process yielded 22 published articles that
      fulfilled our criteria. We found most of the published data that we analyzed to
      be inconsistent, and very little data was obtained on the correlation between LLD
      severity and changes in body posture stability during standing and walking.
      However, the results of the present review study are in line with previous
      observational studies, which describe asymmetry in the lower limbs corresponding
      to biomechanical parameters such as gait kinematics, kinetics, and other
      parameters described during static (standing) postural balance. In future
      investigations, we believe that it might be useful to use and exploit other
      balance-related factors that may potentially influence body posture stability.

PMID- 30116296
TI  - Feasibility of Neurorehabilitation Using a Hybrid Assistive Limb for Patients Who
      Underwent Spine Surgery.
AB  - Recent studies of robotic rehabilitation have demonstrated its efficacy for
      neurological disorders. However, few studies have used the Hybrid Assistive Limb
      (HAL) during the early postoperative stage of spine disorders. We aimed to
      evaluate the safety and efficacy of HAL treatment during the early postoperative
      period for spine disorder patients. We retrospectively identified patients who
      underwent spine surgery and who could complete HAL treatment. We evaluated the 10
      m walking test (10MWT), the modified Gait Abnormality Rating Scale (GARS-M),
      Barthel Index (BI), and the walking index for spinal cord injury II (WISCI II)
      score results before and after robotic rehabilitation. Clinical outcomes were
      compared after treatment. We included nine patients with various spine problems.
      After HAL treatment, the speed during the 10MWT significantly improved from 64.1
      +/- 16.0 to 74.8 +/- 10.8 m/min, and the walking cadence decreased from 102.7 +/-
      17.6 to 92.7 +/- 10.9 steps/min. The BI score also improved from 83.3 +/- 16.0 to
      95.6 +/- 5.8, and the WISCI II score improved from 19.7 +/- 0.5 to 20.0 +/- 0.0.
      Furthermore, the total GARS-M score improved from 6.0 +/- 5.7 to 2.3 +/- 3.3. The
      maximum angles of the trunk swing were improved from 2.2 +/- 1.9 to 1.2 +/- 0.9
      degrees. Neurorehabilitation therapy using HAL for spinal surgery patients was
      considered feasible following spine surgery.

PMID- 30116297
TI  - Optimizing the composition of a synthetic cellulosome complex for the hydrolysis
      of softwood pulp: identification of the enzymatic core functions and biochemical
      complex characterization.
AB  - Background: The development of efficient cellulase blends is a key factor for
      cost-effectively valorizing biomass in a new bio-economy. Today, the enzymatic
      hydrolysis of plant-derived polysaccharides is mainly accomplished with fungal
      cellulases, whereas potentially equally effective cellulose-degrading systems
      from bacteria have not been developed. Particularly, a thermostable multi-enzyme
      cellulase complex, the cellulosome from the anaerobic cellulolytic bacterium
      Clostridium thermocellum is promising of being applied as cellulolytic nano
      machinery for the production of fermentable sugars from cellulosic biomass.
      Results: In this study, 60 cellulosomal components were recombinantly produced in
      E. coli and systematically permuted in synthetic complexes to study the function
      activity relationship of all available enzymes on Kraft pulp from pine wood as
      the substrate. Starting from a basic exo/endoglucanase complex, we were able to
      identify additional functional classes such as mannanase and xylanase for optimal
      activity on the substrate. Based on these results, we predicted a synthetic
      cellulosome complex consisting of seven single components (including the
      scaffoldin protein and a beta-glucosidase) and characterized it biochemically. We
      obtained a highly thermostable complex with optimal activity around 60-65 
      degrees C and an optimal pH in agreement with the optimum of the native
      cellulosome (pH 5.8). Remarkably, a fully synthetic complex containing 47 single
      cellulosomal components showed comparable activity with a commercially available
      fungal enzyme cocktail on the softwood pulp substrate. Conclusions: Our results
      show that synthetic bacterial multi-enzyme complexes based on the cellulosome of
      C. thermocellum can be applied as a versatile platform for the quick adaptation
      and efficient degradation of a substrate of interest.

PMID- 30116298
TI  - Protein folding prediction in the HP model using ions motion optimization with a
      greedy algorithm.
AB  - Background: The function of a protein is determined by its native protein
      structure. Among many protein prediction methods, the Hydrophobic-Polar (HP)
      model, an ab initio method, simplifies the protein folding prediction process in
      order to reduce the prediction complexity. Results: In this study, the ions
      motion optimization (IMO) algorithm was combined with the greedy algorithm
      (namely IMOG) and implemented to the HP model for the protein folding prediction
      based on the 2D-triangular-lattice model. Prediction results showed that the
      integration method IMOG provided a better prediction efficiency in a HP model.
      Compared to others, our proposed method turned out as superior in its prediction
      ability and resilience for most of the test sequences. The efficiency of the
      proposed method was verified by the prediction results. The global search
      capability and the ability to escape from the local best solution of IMO combined
      with a local search (greedy algorithm) to the new algorithm IMOG greatly improve
      the search for the best solution with reliable protein folding prediction.
      Conclusion: Overall, the HP model integrated with IMO and a greedy algorithm as
      IMOG provides an improved way of protein structure prediction of high stability,
      high efficiency, and outstanding performance.

PMID- 30116299
TI  - Long-term evaluation of NEDA-3 status in relapsing-remitting multiple sclerosis
      patients after switching from natalizumab to fingolimod.
AB  - Background: Natalizumab significantly reduces the disease activity in patients
      with relapsing-remitting multiple sclerosis but due to the risk of progressive
      multifocal leukoencephalopathy it is often discontinued. Fingolimod is seen as an
      alternative, but there are no long-term analyses of the efficacy of fingolimod in
      this setting using the no evidence of disease activity (NEDA)-3 criteria. We
      provide an assessment of patients who discontinued natalizumab and switched to
      fingolimod or other treatments by evaluating the proportion of patients who
      fulfil NEDA-3 criteria after prolonged follow-up periods. Methods: We conducted a
      retrospective observational study of multiple sclerosis patients, who were
      treated with continuous natalizumab or who had switched to fingolimod or other
      treatments after natalizumab discontinuation. We assessed NEDA-3 status, annual
      relapse rate and determined the odds ratio between disease course after treatment
      switch and other patient and treatment characteristics. Results: A total of 61
      patients on continuous natalizumab treatment and 53 patients who switched from
      natalizumab to fingolimod or other treatments were accompanied for up to 5 years.
      While the proportion of natalizumab patients fulfilling NEDA-3 criteria remained
      stable at 90% during the entire follow-up period, the proportion of patients
      switching to fingolimod or other therapies dropped to 76.7% in the first year
      after discontinuation, and to 50% in the years thereafter. While the median
      Expanded Disability Status Scale remained stable and the percentage of relapsing
      patients did not change significantly, recurring magnetic resonance imaging
      activity was found in up to 42% of the patients after switching from natalizumab
      to other treatments. New disease activity was significantly correlated with
      extended treatment gap between natalizumab discontinuation and the start of a new
      therapy. Discussion: Patients remain clinically stable after discontinuing
      natalizumab and switching to other therapies. However, when considering NEDA-3
      criteria, a considerable proportion of patients show disease reactivation.
      Careful monitoring and early evaluation of alternatives is necessary after
      switching from natalizumab to other treatments.

PMID- 30116301
TI  - Acute uncomplicated cystitis: is antibiotic unavoidable?
AB  - Background: Acute uncomplicated cystitis in women is one of the most frequently
      diagnosed bacterial infections. Methods: In a pilot, open, noncomparative
      prospective study, 29 nonpregnant, sexually active women with acute uncomplicated
      cystitis were enrolled. The mean age was 28.9 +/- 4.3, range 22-36 years. All
      patients received unique therapy: the nonsteroidal anti-inflammatory drug (NSAID)
      ketoprofen, 100 mg once a day for 5 days, and Canephron, 2 dragees three times a
      day for 1 month. Results: In 2 days, four patients (13.8%) had no tendency to
      improvement; they were considered as nonresponders and antibiotics were
      prescribed for them. The remaining 25 patients (86.2%) showed significant
      improvement and were considered as responders; they continued the therapy with
      ketoprofen and Canephron. In 7 days, 21 patients (72.4%) had no dysuria and
      leucocyturia; they were considered as fast responders to phytotherapy. In four
      patients (13.8%), after 7 days of therapy insignificant dysuria and leucocyturia
      were found; they were considered as slow responders to phytotherapy. All 25
      patients continued the intake of Canephron for 1 month to prevent a relapse. When
      treatment finished, all patients were well. In 6 months, no relapses were
      diagnosed. Conclusion: The majority (86.2%) of young, nonpregnant women with
      acute uncomplicated cystitis were cured by 30 days of phytotherapy combined
      initially (5 days) with the NSAID ketoprofen; an antibiotic was indicated in only
      13.8% of patients. Patients with acute uncomplicated cystitis may be divided into
      three subgroup: nonresponders to phytotherapy; slow responders to phytotherapy;
      fast responders to phytotherapy. Antibiotic therapy is indicated in
      nonresponders, but slow and fast responders may be treated without an antibiotic,
      by phytotherapy with an initial short course of an NSAID only.

PMID- 30116302
TI  - Two-year follow up of silodosin on lower urinary tract functions and symptoms in
      patients with benign prostatic hyperplasia based on prostate size: a prospective
      investigation using urodynamics.
AB  - Background: The aim of this research was to investigate intermediate-term effects
      of silodosin on lower urinary tract functions and symptoms in patients with lower
      urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) according
      to prostate size, using urodynamics. Methods: A total of 70 untreated outpatients
      with a prostate volume <40 ml [small prostate (SP) group] and 70 with prostate
      volume ?40 ml [large prostate (LP) group] were prospectively enrolled and treated
      by monotherapy with silodosin for 24 months. Changes in parameters from baseline
      to 3 months and 24 months after silodosin administration were assessed based on
      LUTS, voiding and storage function. In addition, withdrawal rates of silodosin
      due to insufficient effects were compared between the two groups and factors to
      influence the withdrawal were investigated. Results: The International Prostate
      Symptom Score (IPSS), bladder outlet obstruction index (BOOI), and detrusor
      overactivity (DO) improved significantly for the 2-year follow up in both groups
      as compared with the baseline. IPSS, BOOI and DO improved by 40.4%, 41.3%, and
      48.1% in the SP group, 32.7%, 35.9%, and 34.4% in the LP group at 3 months,
      while, 44.3%, 43.5%, and 63.0% in the SP group, 22.6%, 21.1%, and 34.4% in the LP
      group at 24 months, respectively. Improvement rates in the IPSS and BOOI at 3
      months were maintained until 24 months in the SP group, but decreased in the LP
      group. Storage function improvements continued in both groups for 2 years.
      Dropout rate due to unsatisfactory effects was significantly higher in the LP
      group (20% versus 8.6%). Maximum flow rate, BOOI, and intravesical prostatic
      protrusion had a significant influence on the withdrawal of silodosin treatment
      in the LP group. Conclusions: Silodosin significantly improved lower urinary
      tract functions for 2 years in patients with LUTS/BPH, regardless of prostate
      size. However, LUTS and BOO improvements tended to decrease in patients with a
      large prostate (>40 ml) in the intermediate term.

PMID- 30116300
TI  - Can inflammation be resolved in Alzheimer's disease?
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by
      progressive memory loss and dementia. Accumulating evidence suggests that
      inflammation is involved in the pathogenesis of AD. Epidemiological studies
      suggest that use of anti-inflammatory drugs is associated with a lower incidence
      of AD. However, clinical trials with anti-inflammatory drugs have not been
      successful. Recent studies have shown that inflammation is resolved by a process
      that is mediated by a group of lipid mediators, so called specialized pro
      resolving lipid mediators (SPMs). Unlike anti-inflammatory strategies, which
      usually involve inhibition of the synthesis of inflammatory mediators,
      stimulating the resolution of inflammation is aimed at ending inflammation in a
      similar fashion as under normal physiological conditions. We have previously
      shown that pathways of resolution are impaired in AD. Moreover, we found that
      SPMs can improve neuronal survival and increase microglial phagocytosis of
      amyloid beta (Abeta) in in vitro studies, indicating that stimulating resolution
      of inflammation may be a potential therapeutic target in AD. In this review, we
      summarize recent findings regarding resolution of inflammation in AD. We also
      discuss possible strategies to stimulate the resolution of inflammation in AD,
      specifically focusing on signaling pathways, including SPMs, their receptors and
      enzymes involved in their formation.

PMID- 30116303
TI  - Best practice in the diagnosis and treatment of varicocele in children and
      adolescents.
AB  - A varicocele is an abnormal dilation of the pampiniform plexus of veins in the
      scrotum which begins at puberty in approximately 15% of males. Although common in
      the general population and often asymptomatic, varicoceles are associated with
      gonadal dysfunction including testicular atrophy, infertility, and hypogonadism
      in a subset of men diagnosed later in life. Because of the high prevalence and
      uncertain pathogenesis, definitive management guidelines for varicoceles
      diagnosed in the pediatric and adolescent population remain poorly defined. The
      varicocele is the most common etiology of male factor infertility, and treatment
      in the pediatric and adolescent population may improve semen quality and improve
      fecundity in adulthood. Evaluation of the pediatric and adolescent varicocele
      should include history, physical exam, and measurement of testicular volume with
      orchidometer or ultrasound. Testicular volume differentials and peak retrograde
      flow on Doppler ultrasonography are important factors in risk stratification of
      the pediatric varicocele population. Semen analysis and reproductive endocrine
      assessment should also be considered as part of the workup for adolescent
      patients. A variety of treatment approaches exist for varicocele, and while the
      microsurgical subinguinal approach is the gold standard for the adult population,
      it has yet to be confirmed as superior for the adolescent population. Referral to
      an andrologist for the adolescent patient with varicocele should be considered in
      equivocal cases. While active treatment of varicocele in the pediatric and
      adolescent population is controversial, it is clear that some untreated patients
      will suffer symptoms later in life, while overtreatment remains a concern for
      this large, vulnerable population. Therefore, surveillance strategies and
      improved accuracy in diagnosis of clinically important pediatric varicoceles
      prompting treatment are needed in the future.

PMID- 30116304
TI  - Hyperthyroidism in a complete molar pregnancy with a mature cystic ovarian
      teratoma.
AB  - Background: The hallmark of gestational trophoblastic disease is the production
      of human chorionic gonadotropin (hCG) due to the hyperproliferation of
      extraembryonic trophoblast cells. Previous studies show hCG has thyrotropic
      action due to its structural similarity with thyroid stimulating hormone (TSH)
      molecules. Germ cell tumors represent 15-20% of all ovarian tumors and can be
      malignant or benign. Case presentation: We present a case of a 53-year old
      African American female with a history of hyperthyroidism secondary to a complete
      hydatidiform mole and an associated finding of a mature cystic ovarian teratoma.
      She presented with nausea, vomiting, nervousness, weight gain, abdominal pain and
      a b-hCG of greater than 450,000mIU/mL. A total abdominal hysterectomy with
      bilateral salpingo-oophorectomy was performed and curative for her symptoms. Lung
      nodules were noted with slight increases in b-hCG levels in the months following
      the surgery. Propranolol and methimazole were used to treat the acute
      hyperthyroid symptoms. Conclusion: This case presents the rare occurrence of a
      complete hydatidiform mole causing hyperthyroidism and an associated finding of a
      mature cystic teratoma. It also highlights the importance of monitoring b-hCG
      levels following a complete molar pregnancy due to an increased risk of
      choriocarcinoma.

PMID- 30116305
TI  - Entry points of nutrient arteries at risk during osteotomy of the lesser
      metatarsals: a fresh cadaveric study.
AB  - Background: Osteotomies of the lesser (second to fourth) metatarsals are often
      used to correct forefoot deformities. However, certain areas of the lesser
      metatarsals where arteries may be prone to damage during surgery, and the
      resulting nonunion and delayed union could cause serious problems. This study
      sought to identify the nutrient arteries of the lesser metatarsals and to
      determine how osteotomy could injure these vessels. Methods: Enhanced computed
      tomography scans of 21 ft (male, n = 10; female, n = 11; mean age 78.6 years at
      the time of death) were assessed. Twenty-one lower limbs in 21 cadaveric
      specimens were injected with barium via the external iliac artery, and the points
      at which the nutrient arteries entered the lesser metatarsals were identified on
      axial and coronal images. Results: Each nutrient artery entered the lateral or
      medial plantar aspect of the lesser metatarsal in the middle third (just proximal
      to the middle point of the metatarsal) or proximal third obliquely from a distal
      direction. The mean +/- standard deviation (SD) distances from the dorsal plane
      of the second, third, and fourth metatarsals to the point of entry of the
      nutrient artery in the axial plane were 8.2 +/- 1.5, 7.6 +/- 1.2, and 7.6 +/- 1.5
      mm, respectively. The mean +/- SD distances from the distal epiphysis to the
      point of entry of the nutrient artery into the second, third, and fourth
      metatarsals in the coronal plane were 3.3 +/- 1.1, 3.1 +/- 1.0, and 2.8 +/- 1.2
      mm, respectively. The mean +/- SD distances from the distal epiphysis to the
      point of entry of the nutrient artery into the second, third, and fourth
      metatarsals in the coronal plane were 46.0 +/- 5.2, 40.9 +/- 2.6, and 39.1 +/-
      3.7 mm, respectively. The mean +/- SD distances from the proximal epiphysis to
      the entry point of the nutrient artery into the second, third, and fourth
      metatarsals in the coronal plane were 23.8 +/- 4.7, 25.8 +/- 4.3, and 25.0 +/-
      3.2 mm, respectively. Conclusions: Distal metatarsal osteotomies might be safer
      than shaft or proximal osteotomy to avoid disruption of the nutrient artery,
      leading to delayed consolidation of the osteotomy and nonunion.

PMID- 30116306
TI  - Cystic mediastinal mass.
AB  - Case presentation: A 32-year-old woman with no other medical history presented
      with 1-month history of fever, weight loss and dyspnoea. On examination she had
      elevated jugular venous pressure and tachycardia. Her chest X-ray
      posterioranterior view (figure 1A) showed a rounded mass in the right
      cardiophrenic angle obscuring the right atrial margin, producing a 'silhouette'
      sign. Echocardiography showed a large cystic mass with thickened pericardium,
      lateral to the right atrium, causing right atrial compression (figure 1B). CT
      image of the chest showed a cystic lesion compressing the right atrium with
      thickened pericardium (figure 2A). There were no other lesions found in the lungs
      or other organs. Laboratory tests showed elevated erythrocyte sedimentation rate
      (ESR: 96 mm/hour) and C reactive protein (CRP: 32 mg/L). Excision of the mass
      with partial pericardiectomy was done. Intraoperatively, there was a cyst with
      thickened pericardial wall and thick yellowish brown fluid. Histopathology of the
      tissue is shown in figure 2B.Figure 1(A) Chest X-ray posterioranterior view
      showing a rounded mass in the right cardiophrenic angle. (B) Transthoracic
      echocardiography apical four-chamber view showing the cystic mass.Figure 2(A) CT
      of the chest sagittal view showing cystic lesion compressing the right atrium
      with thickened pericardium. (B) Histopathology specimen of the pericardial
      tissue. Question: What is the diagnosis and what should be the management
      strategy?Congenital pericardial cyst and no further evaluation required.Features
      are suggestive of tuberculous pericardial cyst and needs treatment with
      antituberculosis regimen.Features suggestive of pericardial hydatid cyst and
      requires treatment with albendazole.Features are suggestive of viral pericarditis
      with encysted effusion.

PMID- 30116307
TI  - Clinical significance of optical coherence tomography-guided angioplasty on
      treatment selection.
AB  - The present study aimed to observe whether optical coherence tomography (OCT)
      guided angioplasty is able to provide useful clinical information beyond that
      obtained by angiography as well as provide recommendations for physicians that
      may improve treatment selection. This prospective study included 83 patients with
      coronary artery disease (>18 years) undergoing coronary angiography (CAG) for ST
      elevation myocardial infarction (n=13), non-ST-elevation myocardial infarction
      (n=19), stable angina (n=22), unstable angina (n=10), silent ischemia (n=11), or
      elective percutaneous coronary intervention (n=8). Following the initial CAG (CAG
      pre), the patients underwent OCT before angioplasty (OCT-pre, 24 patients), after
      angioplasty (OCT-post, 22 patients), or both (37 patients). The thrombus burden,
      calcification and plaque dissection or rupture were compared between the OCT-pre
      and CAG-pre recordings. Following angioplasty, stent malapposition, suboptimal
      stent deployment, suboptimal stent lesion coverage, and edge dissection were
      compared between OCT-post and CAG-post alone. Among the 83 patients, 45.7% had
      single-vessel and 54.3% had multiple-vessel disease. OCT pre- and post
      angioplasty revealed significantly more information on the procedure than CAG
      alone. This clinical information changed the clinical strategies in 41/83 (49.4%)
      patients, including 58 modifications of therapeutic strategy (69.9%, 58/83):
      Thrombus aspiration in 2 cases (2.4%), administration of glycoprotein IIb/IIIa
      inhibitors in 8 cases (9.6%), additional balloon inflation in 23 cases (27.7%),
      additional stent implantation in 17 cases (20.5%), avoiding stent implantation in
      4 cases (4.8%), collateral intervention in 2 cases (2.4%), and guidewire
      reposition in 2 cases (2.4%). In conclusion, OCT-pre and OCT-post provided
      additional clinical information beyond that obtained by angiography alone, which
      resulted in modification of the treatment strategies in half of the included
      patients.

PMID- 30116309
TI  - An anatomical study of the spinous process of the seventh cervical vertebrae
      based on the three-dimensional computed tomography reconstruction.
AB  - Palpation of the seventh cervical vertebra (C7) is important for the diagnosis
      and treatment of neck and chest conditions. However, the spinous process of C7
      (C7-SP) displays an anatomical deviation among individuals. The present study
      aimed to clarify anatomic characteristics of C7-SP by using a three-dimensional
      (3D) computed tomographic (CT) reconstruction technique. A total of 245 subjects
      meeting the selection criteria were examined. After CT scanning, the images were
      reconstructed in 3D. All subjects were grouped according to their deviation of C7
      SP: Deviating to the right (DR group), deviating to the left (DL group) and no
      deviation (ND group). Three distances and three angles were recorded on C7-SP.
      The vertical distances between the borders of the left and right transverse
      processes and the tip of the SP, were termed DLTS and DRTS, respectively. The
      length of the SP was also determined. The angle of the SP deviation was referred
      to as ?alpha, the angle between the SP axis and the line crossing the tips of the
      transverse processes was referred to as ?beta and the angle between the vertebral
      body axis and the SP axis was referred to as ?gamma. Among the three groups,
      differences in ?alpha and ?beta were statistically significant (P<0.05).
      Furthermore, the DLTS was significantly different between the DL and ND groups
      (P<0.05). In addition, a significant difference in the DRTS was identified
      between the DR and ND groups (P<0.05). 3D CT reconstruction was reliable for
      studying anatomic characteristics of C7-SP. Based on this, patients may be
      preliminarily grouped according to the deviation of their C7-SP and the
      measurement of the C7-SP may guide clinical diagnoses and treatments.

PMID- 30116308
TI  - Analysis of FK506-mediated functional recovery and neuroprotection in a rat model
      of spinal cord injury indicates that EGF is modulated in astrocytes.
AB  - The present study aimed to evaluate whether the application of tacrolimus (FK506)
      could improve functional recovery in spinal cord injury (SCI) rat models by
      activating astrocytes, and to further investigate the underlying mechanisms of
      this action. Male Sprague-Dawley rats (n=56) were used to establish moderate SCI
      models, which were induced at the T10 spinal segment by dropping a 10-g weight
      from a height of 25 mm using a New York University Impactor device. The rats were
      randomly separated into the FK506 or control group (n=28 per group). Rats were
      treated with FK506 (0.5 mg/kg) or saline intravenously 30 min after sustaining
      the injury. Functional recovery was evaluated over 42 days following the injury,
      and epidermal growth factor (EGF) levels were detected. The astrocytes were
      treated with FK506 in vitro, and the EGF mRNA and protein expression levels were
      analyzed using reverse transcription-quantitative polymerase chain reaction and
      ELISA, respectively. DNA microarray analysis was also performed to evaluate the
      genes in astrocytes. Rats in the FK506 group had improved locomotor functional
      recovery compared with those of control group. Furthermore, FK506 upregulated EGF
      expression of astrocytes both in vivo and in vitro. Subsequent to treatment with
      FK506-conditioned medium (CM), the length of neuronal cells increased 61.06% on
      the first day, and increased 56.4% on the third day compared with those of C-CM
      group. Furthermore, addition of anti-EGF neutralizing antibodies could interrupt
      the promotion of neurite outgrowth by FK506-CM. The present study indicates that
      astrocytes have an important role as mediators of FK506-improved spinal cord
      function recovery, and this partially clarifies the role of cell-cell interaction
      through modulating EGF in this process.

PMID- 30116310
TI  - Dynamic expression of Epac and Rap1 in mouse oocytes and preimplantation embryos.
AB  - Cyclic adenosine monophosphate (cAMP) is an important secondary messenger that
      has long been recognized to control the initiation of meiosis through the
      activation of protein kinase A (PKA) in mammalian oocytes. However, PKA is not
      the only target for cAMP. Recent studies on cAMP-dependent and PKA-independent
      pathways suggest that Ras-related protein-1 (Rap1) is activated through its cAMP
      responsive guanine exchange factors (cAMP-GEFs), which comprises the involvement
      of exchange proteins directly activated by cAMP (Epac) in various cellular
      processes. The aim of the present study was to investigate the possible
      implication of a cAMP/Epac/Rap1 pathway in mouse oocytes and embryos. Reverse
      transcription polymerase chain reaction and immunohistochemistry assays
      demonstrated the expression of Epac and Rap1 in oocytes and embryos at different
      stages. Immunofluorescene demonstrated that Epac and Rap1 had different dynamic
      subcellular localizations and expression patterns in oocytes and embryos at
      different stages. It was therefore indicated that Epac and Rap1 may have multiple
      and specific functions during oocyte maturation and embryonic development.

PMID- 30116311
TI  - Antitumor necrosis factor-alpha antibodies as a noveltherapy for hepatocellular
      carcinoma.
AB  - Hepatocellular carcinoma (HCC) accounts for many cases of cancer-associated
      mortality. Tumor necrosis factor (TNF)-alpha is a key mediator of tumor-promoting
      inflammation. It has been demonstrated that anti-TNF-alpha treatments have
      preclinical benefits for multiple types of cancer, however their potential for
      treating HCC remains unclear. Through fluorescence-activated cell sorter analysis
      and enzyme-linked immunosorbent assay, the results of the current study indicated
      that TNF-alpha was strongly expressed in HCC tissues and the HCC cell lines HepG2
      and Hep3B. In vitro, anti-TNF-alpha antibodies (infliximab and etanercept)
      decreased HCC cell viability via antibody-dependent cell-mediated cytotoxicity
      and complement-dependent cytotoxicity effects. Infliximab treatment also
      significantly increased apoptosis in HepG2 and Hep3B cells compared with controls
      (P<0.001 and P<0.05, respectively). In vivo, anti-TNF-alpha treatment delayed HCC
      progression as indicated by the significantly prolonged survival time in an HCC
      xenograft mouse model (P=0.0009). Further analyses revealed that anti-TNF-alpha
      treatment significantly decreased the expression of pro-inflammatory cytokines,
      including TNF-alpha (P<0.01), interleukin (IL)-1beta (P<0.05), IL-6 (P<0.05) and
      IL-17 (P<0.05) and induced apoptosis in HCC tumors. The results of the current
      study suggest that TNF-alpha is a potential target for novel therapeutic
      strategies to treat HCC. Anti-TNF-alpha treatments compromised HCC tumor
      progression by inducing cell death and decreasing levels of pro-inflammatory
      cytokines.

PMID- 30116312
TI  - Anti-neuropilin-1 monoclonal antibody suppresses the migration and invasion of
      human gastric cancer cells via Akt dephosphorylation.
AB  - Neuropilin-1 (NRP-1) is involved in a range of physiological and pathological
      processes, including neuronal cell guidance, cardiovascular development,
      immunity, angiogenesis and the pathogenesis of cancer. Targeting of NRP-1 is
      considered to be a potential cancer therapy and a number of approaches have been
      investigated, including the use of small interfering RNA, peptides, soluble NRP
      antagonists and monoclonal antibodies. The present study used a novel anti
      neuropilin-1 monoclonal antibody (anti-NRP-1 mAb) to investigate its potential
      anti-tumor effects on human gastric cancer cells in vitro and in vivo, as well as
      its underlying mechanisms of action. Using an MTT assay, it was observed that
      anti-NRP-1 mAb (<150 ug/ml) had no effects on the viability of gastric cancer
      cell line BGC-823, while a Boyden chamber assay indicated that treatment with
      anti-NRP-1 mAb suppressed the migration and invasion of BGC-823 cells. Western
      blot analysis also demonstrated that phosphorylation of Akt was reduced in BGC
      823 cells treated with anti-NRP-1 mAb. Furthermore, anti-NRP-1 mAb suppressed the
      growth of gastric cancer xenograft tumors and downregulated the expression of
      vascular endothelial growth factor proteins within tumors in nude mice. These
      data indicate the potential effects of anti-NRP-1 mAb on malignant tumors and
      suggest that inhibition of NRP-1 function with anti-NRP-1 mAb may be a novel
      therapeutic approach in the treatment of cancer.

PMID- 30116313
TI  - Effects of mulberry leaf on experimental hyperlipidemia rats induced by high-fat
      diet.
AB  - Hypercholesterolemia is a major risk factor for cardiovascular disease. Mulberry
      leaf (ML) is a Traditional Chinese Medicine used to treat hyperlipidemia in
      clinical settings. The aim of the present study was to identify the potential
      effect and possible target of ML in anti-hypercholesterolemia. Male Sprague
      Dawley rats were fed with a high-fat diet and treated with ML for 5 weeks. Blood
      lipid levels, total cholesterol (TC) and total bile acid (TBA) in the liver and
      feces were measured to assess the effects of ML on hypercholesterolemia. Harris's
      hematoxylin staining and oil red O staining was applied to observe the
      pathological change and lipid accumulation in the liver. Immunohistochemical
      assay was performed to observe the location of expressions of scavenger receptor
      class B type I and low-density lipoprotein (LDL) receptor (-R), and western
      blotting was applied to determine the protein expression of ATP-binding cassette
      transporter G5/G8 (ABCG5/8), nuclear transcription factor peroxisome proliferator
      activated receptor-alpha (PPARalpha), farnesoid-X receptor (FXR) and cholesterol
      7alpha-hydroxylase 1 (CYP7A1). The results demonstrated that ML treatment reduced
      serum TC and LDL-cholesterol levels, and liver TC and TBA contents; increased
      serum HDL-C levels, and fecal TC and TBA contents; and alleviated hepatocyte
      lipid degeneration. In addition, ML treatment inhibited liver LDL-R, PPARalpha
      and FXR protein expression, promoted protein expression of CYP7A1, and maintained
      the ratio of ABCG5/ABCG8. The findings of the present study provide a positive
      role of ML on cholesterol clearance via promoting cholesterol and TBA execration
      via FXR- and CYP7A1-mediated pathways; RCT regulation may be a potential
      mechanism of ML on anti-hypercholesterolemia.

PMID- 30116314
TI  - Macrophages ameliorate bone marrow inflammatory injury and promote hematopoiesis
      in mice following hematopoietic stem cell transplantation.
AB  - Bone marrow macrophages have been demonstrated to serve a critical role in
      promoting maintenance and retention of hematopoietic stem cells (HSCs). Our
      previous study indicated increased macrophages infiltration in bone marrow after
      HSC transplantation (HSCT). However, it is not well understood whether
      macrophages affect hematopoietic reconstitution after HSCT. The present study
      aimed to investigate the role of macrophages in hematopoietic reconstitution
      after HSCT. BALB/c mice were divided into HSCT, HSCT+Clodronate Liposomes,
      HSCT+PBS Liposomes, HSCT+RS102895 and HSCT+Vehicle groups and sacrificed on day
      7, 14, 21, 28 and 35 after HSCT. Analysis was performed to detect the changes of
      bone marrow pathology by H&E staining and the number of macrophages was assessed
      by immunohistochemical staining and western blot analysis. The number of c
      kit+sca-1+ and c-kit+ was measured by flow cytometry. Mice with a depletion of
      bone marrow macrophages displayed significantly reduced overall survival, delayed
      hematopoietic recovery, a reduced number of hematopoietic stem/progenitor cells
      and bone marrow cells as well as exaggerated bone marrow injury. However,
      compared with the HSCT+Vehicle group, mice with an increased number of bone
      marrow macrophages exhibited no difference of overall survival, had accelerated
      hematopoietic reconstitution, a higher number of hematopoietic stem/progenitor
      cells and bone marrow cells and ameliorated bone marrow injury. In conclusion,
      the present study indicated that bone marrow macrophages serve a protective role
      in bone marrow injury and may promote hematopoiesis in mice after HSCT,
      suggesting manipulation of macrophages may be a novel strategy for improving the
      efficacy of HSCT.

PMID- 30116315
TI  - Effect of thrombelastography on timing of coronary artery bypass grafting.
AB  - The guiding value of thrombelastography (TEG) on the selection of surgical timing
      for patients scheduled for coronary artery bypass grafting (CABG) was
      investigated. A total of 90 subjects with acute coronary syndrome (ACS) treated
      between February 2014 and December 2016 in Henan Provincial People's Hospital
      were recruited. The patients received dual antiplatelet therapy (DAPT) and were
      scheduled for CABG. Subjects were randomly allocated into two groups, TEG group
      (n=45) and non-TEG group (n=45). Patients in the TEG group withheld medications
      at 24 h prior to surgery and received TEG examination. Based on maximum amplitude
      of adenosine diphosphate (MAADP), subjects were further grouped into three sub
      groups with MAADP <35 mm, 35-50 mm, and >50 mm, and accordingly received CABG
      within 1 day, 3-5 days and 5 days later, respectively. Subjects in the control
      group (non-TEG group) received CABG 5-7 days after medication withdrawal. Chest
      drainage volume within 24 h after surgery and red blood cell transfusion during
      perioperative period were compared. Other recorded parameters were incubation
      period, intensive care unit length of stay, hospital stay, incidence of 30-day
      adverse events and readmission rate. The average waiting time before CABG for
      patients of TEG group was shorter compared with the commonly recommended time.
      The red blood cell transfusions during perioperative period of subjects in TEG
      group and non-TEG group were significantly different (P=0.23). The median
      hospital stay of subjects in TEG group was shorter than that of non-TEG group
      (P=0.037). The bleeding amount of patients in TEG group was 220.16+/-80.56 ml,
      which was significantly lower than that of non-TEG group (435.29+/-90.16). The
      difference was statistically significant (P=0.032). The results suggested that
      TEG assay-based evaluation of platelet function for patients scheduled for CABG
      reasonably guides surgeons with appropriate surgical timing and reduces the
      amount of time patients wait to be treated.

PMID- 30116316
TI  - MicroRNA-199a-5p aggravates primary hypertension by damaging vascular endothelial
      cells through inhibition of autophagy and promotion of apoptosis.
AB  - The present study investigated the expression of microRNA (miRNA or miR)-199a-5p
      in the peripheral blood of patients with primary hypertension, and examined its
      mechanism of action in vascular endothelial cell injury induced by hypertension.
      A total of 57 patients with primary hypertension, who were treated at the
      Affiliated Hospital of Qingdao University (Qingdao, China) between December 2014
      and November 2015 were included in the present study. Peripheral blood was
      collected from all patients. The expression of miR-199a-5p was measured using
      reverse-transcription quantitative polymerase chain reaction analysis. Human
      umbilical vein endothelial cells (HUVECs) were divided into negative control, miR
      199a-5p mimics and rescue (co-transfected with miR-199a-5p mimics and inhibitor)
      groups. After transfection, the proliferation and apoptosis of HUVECs were
      evaluated by a Cell Counting Kit-8 assay, a bromodeoxyuridine incorporation assay
      and flow cytometry. Western blot analysis was used to determine the expression of
      proteins involved in autophagy-associated and adenosine monophosphate kinase
      (AMPK)/unc-51 like autophagy activating kinase 1 (ULK1) signaling pathways. Laser
      scanning confocal microscopy and electron microscopy were used to observe the
      autophagy of HUVECs. The expression of miR-199a-5p was elevated in peripheral
      blood of patients with hypertension, and was correlated with the progression of
      hypertension. Overexpression of miR-199a-5p inhibited the proliferation and
      promoted the apoptosis of HUVECs. Upon expression of miR-199a-5p, the transition
      between microtubule-associated proteins 1A/1B light chain 3B (LC3B)I and LC3BII
      proteins was inhibited, the expression of p62 protein was upregulated. In
      addition, miR-199a-5p decreased the numbers of autophagosomes and autolysosomes
      in HUVECs. The present study demonstrated that expression of miR-199a-5p is
      positively correlated with the severity of hypertension. Expression of miR-199a
      5p aggravated vascular endothelial injury by inhibiting autophagy and promoting
      the apoptosis of HUVECs via downregulation of the AMPK/ULK1 signaling pathway.

PMID- 30116317
TI  - Changes in osteogenic gene expression in hypertrophic chondrocytes induced by SIN
      1.
AB  - The molecular mechanisms underlying osteoarthritis (OA) and Kashin-Beck disease
      (KBD) remain poorly understood. Hypertrophic chondrocytes serve an important role
      in the development of both OA and KBD, whereas oxidative stress can contribute to
      the pathological progression of cartilage damage. Therefore, the aim of the
      present study was to detect altered expression of osteogenesis-related genes in
      hypertrophic chondrocytes, following treatment with 3-morpholinosydnonimine (SIN
      1). ATDC5 cells were induced to develop into hypertrophic chondrocytes via
      Insulin-Transferrin-Selenium. The appropriate concentration and time of SIN-1
      treatment was determined via MTT assay. Following hypertrophic chondrocyte
      stimulation with SIN-1, a liquid chip was analyzed using a polymerase chain
      reaction (PCR) array. Reverse transcription-quantitative PCR was conducted on
      individual genes to validate the array-based data. Analyses of protein-protein
      interactions, gene ontology functions and Kyoto Encyclopedia of Genes and Genomes
      pathway enrichment of the differentially expressed genes were also performed. A
      total of 6 upregulated and 34 downregulated genes were identified, including the
      mothers against decapentaplegic homolog (Smad) family (Smad1-4), bone
      morphogenetic proteins and their receptors (Bmp2, Bmp3, Bmpr1alpha and
      Bmpr1beta), and matrix metalloproteinases (MMP2,-9 and-10). These genes are
      associated with collagen biology, transcriptional control, skeletal development,
      bone mineral metabolism, and cell adhesion. SIN-1 induced death of hypertrophic
      chondrocytes likely through TGF-beta/Smad or BMP/Smad pathways. Oxidative-stress
      dependent induction of abnormal gene expression may be associated with
      chondronecrosis in the cartilage of patients with OA or KBD.

PMID- 30116318
TI  - Effects of vitamin D on apoptosis of T-lymphocyte subsets in neonatal sepsis.
AB  - Effect of vitamin D on apoptosis of peripheral blood T-lymphocyte subsets in
      treatment of neonatal sepsis was investigated. A total of 150 neonatal patients
      with sepsis were randomly divided into vitamin D treatment group (observation
      group) and treatment control group, while 100 healthy newborns were selected as
      healthy control group. T-lymphocyte subsets were detected by flow cytometer, the
      levels of tumor necrosis factor-alpha, interleukin-1 and calcitonin were
      determined by double-antibody immunoluminometric assay, and the effect of vitamin
      D on the above indicators in the treatment of sepsis was observed. Serum 25(OH)D
      (22.52+/-5.56 mg/l) in the treatment group was obviously increased compared with
      that in the treatment group (14.85+/-6.14 mg/l) (P<0.05), but the levels in the
      two groups were remarkably lower than that in the normal control group (26.38+/
      6.56 mg/l), and the differences were statistically significant (P<0.05). Cluster
      of differentiation 4 (CD4+) T-lymphocyte subset in sepsis patients was obviously
      reduced compared with that in the healthy control group (P<0.01); the difference
      in comparison of CD8+ T-lymphocyte subset between sepsis patients and healthy
      people was not statistically significant (P>0.05). After treatment for 72 h, CD4+
      T-lymphocytes were increased, and the ratio of CD4+ to CD8+ was close to 1,
      suggesting that the effect was superior to that in the treatment control group.
      The inflammatory factor levels in children with sepsis were evidently higher than
      those in the healthy control group (P<0.01), and high-level states of
      inflammatory factors were significantly improved after treatment with vitamin D
      for 72 h, indicating that the effect was superior to that in the treatment group.
      The results indicated that the prognosis of sepsis patients treated with vitamin
      D is improved, and the mechanism may be achieved by regulating T-lymphocyte
      subsets and inflammatory factors.

PMID- 30116319
TI  - GSH levels affect weight loss in individuals with metabolic syndrome and obesity
      following dietary therapy.
AB  - This study examined the effects of redox status markers on metabolic syndrome
      (MetS) and obesity before and after dietary intervention and exercise for weight
      loss. A total of 103 adults suffering from MetS and obesity participated in this
      study and followed a personalized diet plan for 6 months. Body weight, body fat
      (BF) percentage (BF%), respiratory quotient (RQ) and the redox status markers,
      reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS) and
      protein carbonyls (CARB), were measured twice in each individual, before and
      after intervention. Dietary intervention resulted in weight loss, a reduction in
      BF% and a decrease in RQ. The GSH levels were significantly decreased following
      intervention, while the levels of TBARS and CARB were not affected. Based on the
      initial GSH levels, the patients were divided into 2 groups as follows: The high
      GSH group (GSH, >3.5 umol/g Hb) and the low GSH group (GSH <3.5 umol/g Hb).
      Greater weight and BF loss were observed in patients with high GSH levels. It was
      observed that patients with MetS and obesity with high GSH values responded
      better to the dietary therapy, exhibiting more significant changes in weight and
      BF%. This finding underscores the importance of identifying redox status markers,
      particularly GSH, in obese patients with MetS. Knowing the levels of GSH may aid
      in developing a better design of an individualized dietary plan for individuals
      who wish to lose weight.

PMID- 30116320
TI  - Baicalin attenuates liver hypoxia/reoxygenation injury by inducing autophagy.
AB  - The aim of the present study was to explore the effect of baicalin on liver
      hypoxia/reoxygenation (H/R) injury and the possible mechanism involved. A
      cellular H/R model was established and cells were treated with 50, 100 and 200
      umol/l baicalin. Following reoxygenation for 6 h, cell viability, lactate
      dehydrogenase (LDH), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax),
      caspase 3 and cleaved caspase 3 were assessed. Furthermore, levels of endoplasmic
      reticulum stress markers binding of immunoglobulin protein (BIP) and
      CCAAT/enhancer-binding protein homologous protein (CHOP) and autophagy markers
      microtubule-associated proteins 1A/1B light chain 3B (LC3) and beclin 1 were
      measured. To confirm the involvement of autophagy in baicalin-mediated
      attenuation of H/R injury, the autophagy inhibitor 3-methyladenine (3-MA) was
      administered. The results revealed that baicalin administration increased cell
      viability and decreased LDH levels, most notably at a dosage of 100 umol/l.
      Baicalin pretreatment also downregulated the expression of caspase 3, cleaved
      caspase 3 and Bax, while upregulating the expression of Bcl-2. Furthermore, BIP
      and CHOP were decreased while LC3 and beclin-1 were significantly increased by
      baicalin pretreatment. Inhibiting autophagy using 3-MA, resulted in a significant
      decrease in LC3-II, beclin-1 and LDH, as well as increase in the expression of
      BIP, CHOP, caspase 3, cleaved caspase 3 and Bax. Bcl-2 and cell viability were
      also decreased. In conclusion, the results of the present study indicate that
      baicalin exerts a protective effect on liver H/R injury and this may be achieved
      via the induction of autophagy.

PMID- 30116321
TI  - Clinical implication of fasting glucose and systolic/diastolic blood pressure on
      the prevalence of periodontitis in non-diabetic and non-hypertensive adults using
      nationally representative data.
AB  - The prevalence of diabetes mellitus and hypertension is increasing worldwide and
      an association between fasting glucose/blood pressure and periodontitis has been
      suggested. The present study was performed to assess the association between
      fasting glucose and systolic/diastolic blood pressure on the prevalence of
      periodontitis in non-diabetic and non-hypertensive adults using nationally
      representative data. Subgroup analysis was performed to evaluate the combined
      effects of obesity/abdominal obesity and impaired fasting glucose. This study
      involved a cross-sectional analysis using data from the Republic of Korean
      National Health and Nutrition Examination Survey from 2013 to 2015. A total of
      8,341 respondents without diabetes and hypertension over 19 years old without
      missing values were included in the present study. A significant increase was
      observed in the prevalence of periodontitis with increasing systolic blood
      pressure and diastolic blood pressure. The percentage of periodontitis increased
      with increased glucose levels, with similar trends in glycated hemoglobin. The
      odds ratios (ORs) and 95% confidence intervals (CIs) for systolic blood pressure
      of 90<=x<100, 100<=x<110, 110<=x<120, 120<=x<130 and 130<=x<140 were 1.116 (0.591
      2.107), 1.165 (0.624-2.175), 1.238 (0.673-2.278), 1.008 (0.538-1.888) and 1.042
      (0.545-1.993), respectively, when systolic blood pressure <90 was considered as a
      reference. The ORs and 95% CIs for glucose of 90<=x<100, 100<=x<110 and
      110<=x<126 were 1.074 (0.92-1.253), 1.214 (0.986-1.494) and 1.358 (1.005-1.834),
      respectively when glucose <90 was considered as a reference. The association
      between fasting glucose/blood pressure and periodontitis was confirmed by
      multiple logistic regression analyses after adjusting for confounding factors
      among non-diabetic and non-hypertensive Republic of Korean adults. Subgroup
      analysis revealed that higher ORs of periodontitis were observed in participants
      with impaired glucose level and obesity when compared with individuals without
      impaired glucose level or obesity. The results of the present study suggest that
      detection of fasting glucose and blood pressure may serve as a risk indicator for
      periodontal disease.

PMID- 30116322
TI  - Analyses of the efficacy of percutaneous kyphoplasty and alendronate sodium on
      thoracolumbar vertebral fracture and the risk factors of fracture.
AB  - The present study investigated the efficacy of percutaneous kyphoplasty and
      alendronate sodium on thoracolumbar vertebral fracture, and the risk factors
      leading to the recurrence of fracture. In the present study, a total of 80
      patients with thoracolumbar vertebral fracture who were admitted to the
      Affiliated Jiangyin Hospital of Southeast University Medical College between
      January 2014 and March 2016 for combination treatment of percutaneous kyphoplasty
      and alendronate sodium were enrolled. According to the recurrence of fracture,
      the patients were divided into two groups, the observation group (patients with
      fracture recurrence, n=40) and control group (patients with no fracture
      recurrence, n=40). All patients participated in a 1-year follow-up. The
      recurrence of fracture and the site of fracture were identified through the
      clinical symptoms and examination of the spine using magnetic resonance imaging.
      In addition, comparisons of the time of alleviation in numbness of lower limb and
      that in pains in waist and legs were carried out. Furthermore, statistics on the
      adverse reactions during intervention in the two groups were also collected;
      changes in visual analogue scale (VAS) and Oswestry Disability Index (ODI) of
      pains at different time points in two groups were also observed. One-way analysis
      and multivariate analysis were performed to identify the relevant risk factors.
      Alleviation time in numbness of lower legs in patients of the control group was
      significantly earlier than that in the observation group (P<0.05) and the
      alleviation time in pains of the waist and legs of patients in the control group
      was also significantly earlier than that in the observation group (P<0.05).
      Furthermore, the incidence rates of abdominal pain, diarrhea, constipation and
      hypocalcemiain in the control group were also significantly lower compared with
      those in the observation group (P<0.05). One week, one month and one year after
      operation, the scores of VAS of pains and ODI in the control group were
      significantly lower compared with those in the observation group in the same
      period (P<0.05). Lower preoperative bone density and exosmosis of bone cement in
      treatment were the independent risk factors leading to the recurrence of
      fracture. For patients with thoracolumbar vertebral fracture who received the
      combination treatment of percutaneous kyphoplasty and alendronate sodium, there
      underlies an important correlation between the recurrence rate of fracture and
      the preoperative bone density as well as the exosmosis of bone cement in
      operation.

PMID- 30116324
TI  - Development of zoledronic acid functionalized hydroxyapatite loaded polymeric
      nanoparticles for the treatment of osteoporosis.
AB  - The present study formulated a hydroxyapatite (HA)-coated lipid nanoparticle
      loaded with zoledronic acid to treat patients with osteoporosis (OP). HA-coated
      zoledronic acid loaded lipid bilayer nanoparticles (HZL NPs) were prepared using
      methods of extrusion and precipitation. Nanosized particles were prepared with
      the aim of increasing gradual and prolonged drug release and inducing toxicity of
      osteoblasts. Cellular morphology was investigated by scanning electron
      microscopy, which revealed clear spherical shaped NPs ~200 nm in size that could
      treat osteopores in the bone. In addition, a typical biphasic release pattern was
      observed that could be attributed to the presence of drug on the outer surface as
      well as on the inner core of the NPs. There was sustained release behavior
      [38.17+/-2.12% (pH 7.4) and 64.2+/-3.75% (pH 5) at 48 h] of the drug that
      maintained the drug reservoir effect at the bone site. Furthermore, HZL NPs
      increased the cytotoxicity of HFOb 1.19 cells and increased the proportion of
      cells in the early (18.1+/-12.4%), late (28.7+/-3.7%) and necrotic (67.5+/-1.2%)
      phases of apoptosis. Most importantly, HZL in the lipid nanoparticle exhibited a
      strong affinity towards HA, further enhancing its efficacy in the treatment of
      OP.

PMID- 30116325
TI  - Impact of local administration of various doses of dexmedetomidine on ropivacaine
      induced lumbar plexus-sciatic nerve block.
AB  - The present study aimed to investigate the impact of various doses of
      dexmedetomidine (DEX) on ropivacaine (ROP)-induced lumbar plexus-sciatic nerve
      block (LSB). A total of 80 patients who underwent ankle surgery under LSB were
      divided into group R (applied with 30 ml 5% ROP), Dex1 (30 ml 0.5% ROP + 1 ug/kg
      DEX), Dex2 (30 ml 0.5% ROP + 1.5 ug/kg DEX) and Dex3 (30 ml 0.5% ROP + 2 ug/kg
      DEX), with 20 cases in each group. The onset time and duration of sensory and
      motor block, mean arterial pressure (MAP), heart rate (HR), oxygen saturation,
      Ramsay score, serum vascular endothelial growth factor (VEGF) level and adverse
      reactions in the four groups were observed. Results demonstrated that the
      durations of sensory and motor block in group R were shorter than those in groups
      Dex1-3 (P<0.01), followed by the sequence of group Dex1<Dex2<Dex3 (P<0.05). MAP
      and HR in groups Dex1-3 at T2-T5 were significantly lower than those in group R
      (P<0.01), and HR in group Dex3 at T3 and T4 was significantly lower than that in
      groups Dex1 and Dex2 (P<0.05). Ramsay scores in groups Dex1-3 at T2-T4 were
      significantly higher than those in group R (P<0.05). Serum VEGF levels in groups
      Dex2 and Dex3 at T2-T5 were significantly higher than those in group R (P<0.01).
      The incidences of over-sedation, bradycardia and dry mouth in group Dex3 were
      notably higher than those in the other groups. In conclusion, 1.5 ug/kg DEX
      exhibits a superior effect in improving ROP-induced LSB.

PMID- 30116323
TI  - Protective effects of celastrol against gamma irradiation-induced oxidative
      stress in human umbilical vein endothelial cells.
AB  - High-dose ionizing radiation can cause harmful effects on the cardiovascular
      system. Notably, endothelial cells are critical targets in radiation-induced
      damage. gamma radiation exerts its biological effects through the radiolysis of
      water, which further generates ROS and induces lipid peroxidation and DNA damage.
      The present study aimed to evaluate the potential protective effects of celastrol
      against gamma radiation-induced oxidative stress in human umbilical vein
      endothelial cells (HUVECs). HUVECs were exposed to gamma radiation at different
      doses with or without celastrol treatment. Cell viability and cytotoxicity,
      migratory ability, ROS production, lipid peroxidation, oxidative DNA damage and
      antioxidative enzyme levels were evaluated in HUVECs at 24 h post-irradiation. It
      was observed that HUVECs exhibited decreased cell viability, increased
      cytotoxicity and a decreased migratory ability after exposure to 20-Gy gamma
      radiation. Celastrol treatment concentration-dependently reversed these effects.
      gamma irradiation was also demonstrated to increase the production of ROS,
      enhance lipid peroxidation and oxidative DNA damage and decrease the levels of
      SOD, catalase, GST and GPx in HUVECs. These detrimental effects were blocked by
      treatment with celastrol for 24 h. These data suggested that celastrol not only
      attenuated gamma radiation-induced cytotoxicity, but also effectively blocked
      oxidative stress in HUVECs. As an antioxidant agent, celastrol may have potential
      protective effects in HUVECs against gamma irradiation-induced injury.

PMID- 30116326
TI  - Influence of vitamin D deficiency on T cell subsets and related indices during
      spinal tuberculosis.
AB  - The present study investigated the effects of vitamin D deficiency on T cell
      subsets in patients with spinal tuberculosis. In addition, the influence of
      vitamin D deficiency was investigated on the expression of cytokines IL-1beta, IL
      6 and TNF-alpha in intervertebral disc lesions of patients. One hundred and
      seventeen patients with spinal tuberculosis who received operative treatment in
      the Department of Orthopedics in Wuhan City Third Hospital from March 2012 to
      March 2015 were collected. The patients were divided depending upon vitamin D
      content into the control group (64 cases, vitamin D content <25 nmol/l) and
      experimental group (53 cases, vitamin D content >50 nmol/l). Immunofluorescence
      method was applied to determine the content of T cell subsets in both groups of
      patients. Intervertebral disc lesion tissues of two groups of patients were
      obtained during surgery then treated with HE staining and immunohistochemical
      staining. The values of average optical density obtained under light microscope
      were observed as the expression quantities of IL-1beta, IL-6 and TNF-alpha, to
      explore the relationship between vitamin D and the expression of cytokines. When
      vitamin D is lacking, the expression of T lymphocyte subsets in patients with
      spinal tuberculosis significantly decreased. Compared with experimental group,
      the difference was statistically significant (P<0.05). Further, the expression of
      cytokines IL-1beta, IL-6 and TNF-alpha in intervertebral disc lesion tissues of
      patients with spinal tuberculosis were significantly higher than those of
      patients with spinal tuberculosis whose vitamin D content was normal (P<0.05). In
      the control group, vitamin D content was negatively correlated with the
      expression of IL-1beta, IL-6 and TNF-alpha. The expression of T lymphocyte
      subsets in patients with vitamin D deficiency was significantly reduced, and the
      immune function decreased. The expression of IL-1beta, IL-6 and TNF-alpha in
      lesions were significantly higher than those of patients with normal vitamin D
      content. In addition, the lower the content of vitamin D was, the more active the
      expression of inflammatory factors were, which was not conducive to the recovery
      of tuberculosis lesions.

PMID- 30116327
TI  - Targeting cysteine-rich angiogenic inducer-61 by antibody immunotherapy
      suppresses growth and migration of non-small cell lung cancer.
AB  - Non-small cell lung cancer (NSCLC) is the most frequent type of human lung
      cancer; lung cancer is responsible for the highest rates of cancer-associated
      mortality in the world. Cysteine-rich angiogenic inducer-61 (CYR-61) has been
      identified as a tumorigenesis-, development- and metastasis-related gene, and is
      reported to enhance proliferation, migration and invasion through hepatocyte
      growth factor (HGF)-induced scattering and the metastasis-inducing HGF/Met
      signaling pathway in tumor cells and xenograft models. CYR-61 is a protein that
      promotes human lung cancer cell metastasis and is closely related to the
      patient's prognosis in NSCLC. The purpose of the present study was to investigate
      whether CYR-61 may serve as a dual potential target for gene therapy of human
      NSCLC. In the present study, an antibody targeted against CYR-61 (anti-CYR-61)
      was constructed and the therapeutic effects and underlying mechanism of this
      antibody in NSCLC cells and mice with NSCLC was investigated. It was observed
      that NSCLC cell viability, migration and invasion were inhibited while cell
      apoptosis was induced by the neutralization of CYR-61 protein by anti-CYR-61.
      Western blotting demonstrated that extracellular signal-regulated kinase (ERK)
      and protein kinase B (AKT) expression levels in NSCLC cells were decreased
      following treatment with anti-CYR-61. In addition, it was observed that
      inhibition of NSCLC cell viability was achieved by the suppression of the
      epithelial-mesenchymal transition signaling pathway. ERK and AKT phosphorylation
      levels were downregulated in NSCLC cells and tumors following anti-CYR-61
      treatment. Analysis of a murine model indicated that tumor growth was inhibited
      and tumor metastasis was significantly suppressed (P<0.01) following anti-CYR-61
      treatment for CYR-61. In conclusion, CYR-61 may serve as a potential target for
      gene therapy for the treatment of human NSCLC.

PMID- 30116328
TI  - Effect of chitosan combined with hyaluronate on promoting the recovery of
      postoperative facial nerve regeneration and function in rabbits.
AB  - To determine better solutions for postoperative nerve functional recovery, the
      effects of chitosan and hyaluronate on perineural scar formation and neural
      function recovery were investigated in 40 rabbits. Rabbits were randomized into 4
      groups: A (chitosan), B (chitosan + hyaluronate), C (hyaluronate) and D
      (control). The rabbits underwent the same parotidectomy surgery, but different
      materials were used to cover the operated nerves. By evaluating specific
      indicators, including vibrissae motion tests, neural electrophysiological
      examinations and extraneural examinations, it was revealed that the amplitude of
      vibrissae motion of all groups had increased 6 weeks after surgery. The recovery
      of Group B was superior compared with all other groups at 4 and 12 weeks post
      surgery; however no significant differences were detected. Group B exhibited a
      great number of nerve fibers, thicker myelin sheath and greater nerve conduction
      velocity. In summary, the use of a chitosan conduit combined with sodium
      hyaluronate gel may prevent perineural scar formation in facial nerves and
      promote nerve functional recovery.

PMID- 30116329
TI  - Effect of transplantation of cardiac stem cells overexpressing integrin-linked
      kinase on cardiac function of rats with acute myocardial infarction.
AB  - In the present study, we aimed to investigate the effect of transplantation of
      cardiac stem cells (CSCs) overexpressing integrin-linked kinase (ILK) on cardiac
      function of rats with acute myocardial infarction (MI). A total of 60 rats were
      randomly divided into normal saline (NS) group (n=20), green fluorescent protein
      (GFP)-CSC group (n=20) and ILK-CSC group (n=20). In the ILK-CSC group, CSCs in
      rats were transfected with GFP adenovirus vector overexpressing ILK. The rat
      model of MI was established. The cardiac function 4 weeks after transplantation
      was detected via echocardiography, and the exhaustive swimming experiment was
      performed to observe the exercise load capacity. Moreover, Ki-67 and P-H3
      proteins in myocardial tissues of rats were detected via immunohistochemistry,
      and the expression of GFP was observed under a fluorescence microscope. Cells in
      the GFP-CSC group were transfected with the empty GFP adenovirus, while those in
      NS group were not transfected, and other treatments in these two groups were the
      same as those in the ILK-CSC group. Four weeks after transplantation, left
      ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic
      diameter (LVEDD) of rats in the ILK-CSC group were smaller than those in the GFP
      CSC group, but left ventricular ejection fraction (LVEF) (69.88+/-5.61 mm) was
      higher than that in the GFP-CSC group (P<0.05). The exercise time in the ILK-CSC
      group (12.69+/-0.58 min) was longer than that in the GFP-CSC and NS groups
      (P<0.05). The expression levels of Ki-67 and P-H3 proteins in myocardial cells of
      rats in the ILK-CSC group were higher than those in the GFP-CSC and NS groups
      (P<0.05). The number of transplanted cells retained around the infarct region in
      the ILK-CSC group 3 days after transplantation was obviously larger than that in
      the GFP-CSC group (P<0.001). Intramyocardial injection of CSCs overexpressing ILK
      immediately after the establishment of rat model of MI can promote myocardial
      cell proliferation, improve cardiac function and increase exercise capacity of
      rats.

PMID- 30116330
TI  - Effects of atorvastatin on p38 phosphorylation and cardiac remodeling after
      myocardial infarction in rats.
AB  - The aim of the present study was to examine the effects of atorvastatinon p38
      phosphorylation and cardiac remodeling after myocardial infarction in rats. A
      total of 43 rats were randomly divided into the control, sham operation, post
      modeling medication (medication) and post-modeling non-medication (non
      medication) groups. The control group did not receive any treatment. Anterior
      descending arteries of the rats in the medication and non-medication groups were
      ligated, and threading at the anterior descending arteries was conducted for the
      rats in the sham operation group. Atorvastatin (10 mg/kg) was given daily to the
      rats in the medication group, and an equivalent amount of normal saline was given
      daily to the rats in the sham operation group. Four weeks later, the cardiac
      function, morphological changes in the myocardial cells, and the expression of
      tumor necrosis factor-alpha (TNF-alpha) and p38 in each group was detected. At 4
      weeks after treatment, the myocardial infarction size, fibrosis and myocardial
      necrosis of the rats in the medication group was examined compared with those in
      the non-medication group (P<0.05). The cardiac function of the rats in the non
      medication group was significantly lower than that of the rats in the control and
      sham groups (P<0.05), while it was obviously elevated in the medication group
      compared with that in the non-medication group (P<0.05). The expression of TNF
      alpha and phosphorylated p38 of the left ventricle in the non-medication group
      was higher than that in the control group (P<0.05), while it was obviously
      reduced in the non-medication group compared with that in the control group
      (P<0.05). Atorvastatin can improve cardiac remodeling after myocardial infarction
      in rats, which may be associated with its inhibition of p38 phosphorylation and
      its decrease of TNF-alpha expression.

PMID- 30116331
TI  - Leptin promotes the growth of breast cancer by upregulating the Wnt/beta-catenin
      pathway.
AB  - The present study aimed to investigate the role of leptin in the growth of breast
      cancer. In the present study, expression of leptin in tumor tissues and adjacent
      tissues was detected by reverse transcription-quantitative polymerase chain
      reaction. Serum leptin in patients with breast cancer and normal healthy controls
      was detected by ELISA. Different concentrations of leptin were used to treat
      breast cancer cells, and cell proliferation was detected by cell proliferation
      assay. Interactions between leptin and Wnt/beta-catenin were evaluated by western
      blotting. It was demonstrated that expression of leptin mRNA was significantly
      higher in tumor tissues than in adjacent tissues in 43 out of 48 patients. Serum
      level of leptin was significantly higher in patients with breast cancer than in
      normal controls. Leptin promoted the proliferation of breast cancer cells in a
      dose-dependent manner. Leptin significantly increased the expression level of
      beta-catenin in breast cancer cells. Treatment with Wnt inhibitor reduced the
      enhancing effects of leptin on proliferation of breast cancer cells. The results
      of the present study therefore indicate that leptin may promote the growth of
      breast cancer by upregulating the Wnt/beta-catenin pathway.

PMID- 30116332
TI  - Long non-coding RNA TUG1 promotes osteosarcoma cell proliferation and invasion
      through inhibition of microRNA-212-3p expression.
AB  - Taurine upregulated gene 1 (TUG1), a long non-coding RNA (lncRNA), has recently
      been suggested to be associated with the development of osteosarcoma (OS), but
      the underlying molecular mechanism still remains largely unclear. In the present
      study, it was revealed that TUG1 was significantly upregulated whereas miR-212-3p
      was significantly downregulated in OS tissues and cell lines, when compared with
      adjacent non-tumor tissues and normal osteoblasts cell lines, respectively. An
      inverse association between the TUG1 and miR-212-3p expression was also observed
      in OS tissues. Furthermore, TUG1 directly interacted with miR-212-3p and
      negatively regulated the expression of miR-212-3p in OS cells. In vitro
      experiments further indicated that inhibition of TUG1 suppressed the
      proliferation and invasion of OS cells. Furthermore, knockdown of miR-212-3p
      eliminated the suppressive effects of TUG1 inhibition on the proliferation and
      invasion of OS cells. Taken together, these findings demonstrate that TUG1
      promotes OS cell proliferation and invasion by inhibition of miR-212-3p
      expression, thus suggesting that TUG1 may become a potential therapeutic target
      for OS.

PMID- 30116333
TI  - LAP+CD4+ T cells are elevated among the peripheral blood mononuclear cells and
      tumor tissue of patients with hepatocellular carcinoma.
AB  - The purpose of the present study was to investigate the role of latency
      associated peptide (LAP)+CD4+T cells in hepatocellular carcinoma (HCC) immunity.
      Flow cytometric analysis was performed to detect the proportion of LAP+CD4+ T
      cells among the peripheral blood mononuclear cells (PBMCs) of 30 HBV-infected HCC
      patients at the pre-operative and post-operative stages, as well as 30 hepatitis
      B virus (HBV)-infected volunteers as a control group. Furthermore, tumor tissues
      and peri-tumor tissues from 28 patients with HCC, as well as hepatic tissues from
      28 HBV-infected patients with benign lesions were subjected to
      immunohistochemical analysis with double staining for LAP and CD4, and the
      average number of the LAP+CD4+T cells in each visual field was quantified. The
      results indicated that the proportion of LAP+CD4+ T cells in the PBMCs of
      patients with HCC was significantly higher than that in the control group (1.84+/
      0.85 vs. 0.73+/-0.39%, P=0.019), while it was significantly reduced after the
      operation (1.07+/-0.35, P=0.021), but still slightly, if not significantly,
      higher compared with that in the control group (P=0.342). Furthermore, the number
      of LAP+CD4+ T cells per high-magnification microscopic field (magnification,
      *400) in the HCC tissues was 11.25+/-3.00, which was significantly higher than
      that in the peri-cancer tissues (5.75+/-1.00) and that in the HBV-infected
      hepatic tissues around benign lesions (2.61+/-0.83). In peri-cancer tissues,
      LAP+CD4+ T cells were also significantly more abundant than in control tissues.
      Furthermore, in the HCC tissues, LAP+CD4+ T cells were present as clusters in the
      tumor stroma and closely associated with CD4+ T lymphocytes. By contrast, in the
      peri-cancer liver tissues and HBV-infected hepatic tissues around benign lesions,
      LAP+CD4+ T cells were sparsely distributed. LAP+CD4+ T cells have marked
      inhibitory effects, and in the peripheral blood and tumor tissues of patients
      with HCC, they have an important role in the suppression of anti-tumor immunity
      and in the immune evasion of tumor cells.

PMID- 30116334
TI  - Single-incision surgery for gynecomastia using TriPort: A case report.
AB  - Gynecomastia is a common benign condition of the male breast, frequently observed
      in newborns, adolescents and the elderly. Surgical excision remains one of the
      most effective methods for the management of patients with gynecomastia,
      particularly those with fibrosis or a course of >1 year. The present study
      describes two cases of patients with gynecomastia and presents a novel method of
      treatment, combining endoscopic surgery and liposuction using a TriPort, which
      may effectively remove breast tissue and shorten hospitalization time compared
      with a direct excision method.

PMID- 30116335
TI  - Changes in bone mineral density and bone metabolic indexes in ankylosing
      spondylitis mouse model complicated with osteoporosis.
AB  - Changes in bone mineral density and bone metabolic indexes in a model of
      ankylosing spondylitis (AS) mice complicated with osteoporosis (OP) were
      investigated. BLAB/c mice were used as the subjects. AS was induced using
      proteoglycan, and OP was induced using tail suspension method. The mice were
      randomly divided into four groups: AS group, OP group, AS + OP group and negative
      control group. Changes in bone mineral density, bone strength, serum calcium
      (Ca), phosphorus, alkaline phosphatase (ALP) and tartrate-resistant acid
      phosphatase (TRACP), in mice of each group were detected and compared. There were
      statistically significant differences in bone mineral density and bone strength
      among groups. Compared with the negative control group, bone mineral density and
      bone strength in the AS, the OP and the AS + OP groups were significantly
      decreased, and the lowest bone mineral density and bone strength were found in
      the AS + OP group (P<0.05). There were no significant differences in bone mineral
      density and bone strength between the AS group and the OP group. Significant
      differences in serum Ca, ALP and TRACP but not in serum phosphorus were found
      among groups. Compared with the control group, serum levels of Ca and TRACP in
      the AS, the OP and the AS + OP groups were significantly increased, while levels
      of ALP were obviously decreased (P<0.05). Bone destruction in AS mice complicated
      with osteoarthritis was more serious than that in mice with simple AS.

PMID- 30116336
TI  - Clinical significance of changes in IL-6, CRP and S100in serum and NO in
      cerebrospinal fluid insubarachnoid hemorrhage and prognosis.
AB  - Clinical significance of changes in interleukin-6 (IL-6), C-reactive protein
      (CRP) and S100 in serum and NO was investigated in cerebrospinal fluid (CSF) in
      subarachnoid hemorrhage (SAH) and its prognosis. A total of 43 SAH patients and
      23 healthy subjects were selected and divided into cerebral vasospasm (CVS) group
      and non-CVS group, and favorable prognosis group and unfavorable prognosis group
      according to Hunt-Hess grade. The levels of IL-6, CRP, S100 and NO in CSF were
      detected, respectively, followed by statistical analysis of correlation. The
      higher the Hunt grade was, the higher the factor expression was; the expression
      levels of IL-6, CRP, S100 and NO in CSF were gradually increased in CVS group and
      unfavorable prognosis group, and the differences were significant compared with
      those in the control group. There was a positive correlation between the
      expression levels of each of the two factors among IL-6, CRP, S100 and NO in CSF,
      and the differences were statistically significant (P<0.05). The expression
      levels of IL-6, CRP, S100 and NO in CSF in SAH patients are significantly
      increased, showing positive correlations and participating in the occurrence and
      development of SAH, which provide new directions for the early clinical diagnosis
      of SAH.

PMID- 30116337
TI  - Triptolide inhibits vascular endothelial growth factor-mediated angiogenesis in
      human breast cancer cells.
AB  - Triptolide has been demonstrated to induce tumor cell apoptosis. However, the
      role of triptolide in breast cancer angiogenesis remains unclear. The present
      study aimed to investigate the function of triptolide in breast cancer and the
      molecular mechanisms underlying this. The results revealed that triptolide could
      significantly decrease the expression of vascular endothelial growth factor A
      (VEGFA) in Hs578T and MDAMB231 breast cancer cells. Furthermore, human umbilical
      vein endothelial cells were used to perform tube formation and bromodeoxyuridine
      incorporation assays, which demonstrated an antiangiogenic effect of triptolide.
      In addition, the effect of triptolide in vivo was examined in a xenograft mouse
      model, which determined that VEGFA, cluster of differentiation 31 and anti
      proliferation marker protein Ki67 expression in tumor sections was decreased in
      the triptolide treatment group compared with the control group. Western bolt
      analysis was performed to investigate the phosphorylation of extracellular signal
      related kinase (ERK)1/2 and RAC-alpha serine/threonine-protein kinase after
      triptolide treatment, and it's effect on hypoxia inducible factor (HIF)1-alpha
      expression. The results demonstrated that triptolide suppressed ERK1/2 activation
      and HIF1-alpha expression. Furthermore, overexpression of HIF1-alpha could
      partially abrogate the inhibitory effect of triptolide on VEGFA expression. These
      results suggest that triptolide inhibits breast cancer cell angiogenesis in vitro
      and in vivo through inhibiting the ERK1/2-HIF1-alpha-VEGFA axis.

PMID- 30116338
TI  - Expression of Bcl-2 and Bad in hippocampus of status epileptic rats and molecular
      mechanism of intervened recombinant human erythropoietin.
AB  - Injury of hippocampal neurons in status epilepticus (SE) SD rats kindled by
      pentylenetetrazol (PTZ) were studied, and the changes of apoptosis neurons,
      protein expression of Bad and Bcl-2 alone and combined application of
      phosphatidyl inositol 3-kinase (PI3K) inhibitor LY294002 and recombinant human
      erythropoietin (rHuEpo) were evaluated for the possible mechanisms of rHuEpo. The
      SE rats kindled by the PTZ were randomly divided into normal control group
      [normal saline (NS)], model group (PTZ + NS), rHuEpo treated group (PTZ +
      rHuEpo), LY294002 treated group (PTZ + LY294002 + rHuEpo) and LY294002 control
      group (rHuEpo + PTZ + DMSO). Apoptosis of hippocampal neurons was detected by
      TUNEL method; expression of phosphorylation protein kinase B (p-PKB/p-Akt), Bcl-2
      and Bad were detected by immunohistochemistry; the expression of Bcl-2 mRNA, Bad
      mRNA in hippocampal neurons of rats were detected through reverse transcription
      polymerase chain reaction (RT-PCR); the expression of Akt, p-Akt and Bcl-2, Bad
      protein in hippocampal neurons of rats were detected by western blotting. The
      amount of apoptotic neurons was less in the rHuEpo treated group and the LY294002
      control group than in the LY294002 treated group (P<0.05). The expression of p
      Akt protein and Bcl-2 protein increased while the Bad protein decreased
      significantly in the rHuEpo treated group and the LY294002 control group compared
      with the LY294002 treated group (P<0.05). The expression of Bad protein and Bad
      mRNA in hippocampus increased while the p-Akt, Bcl-2, Bcl-2 mRNA decreased
      significantly in the LY294002 treated group compared with the rHuEpo treated
      group (P<0.05). The PI3K/Akt signaling pathway is one of the pathways of rHuEpo
      neuroprotective effects and was confirmed from both the of positive and negative
      aspects. rHuEpo regulates the expression of mitochondrial apoptotic pathway
      related factors Bad and Bcl-2 to inhibit apoptosis and promotes neuronal
      survival.

PMID- 30116339
TI  - Blood platelet and serum bilirubin in the diagnosis of central serous
      chorioretinopathy.
AB  - Diagnostic value of blood platelet (PLT) and serum total bilirubin (TBIL) for
      central serous chorioretinopathy (CSC) was investigated. A total of 537 patients
      with CSC and 182 people with normal physical conditions were selected from June
      2012 to August 2016. The 537 patients included 294 males and 243 females with an
      average age of 45.5+/-17.8 years, and all patients were treated in the Department
      of Ophthalmology of Yantai Hospital of Traditional Chinese Medicine and the
      Department of Ophthalmology of Yantai Liuhuangding Hospital. Clinical data of the
      patients were retrospectively analyzed. The 182 people with normal physical
      conditions included 103 males and 79 females with an average age of 43.6+/-15.2
      years, and they were set as the control group. PLT and TBIL tests at admission
      and after treatment were collected and compared between CSC and the control group
      to analyze the diagnostic values of PLT and TBIL for CSC. PLT level in the CSC
      group was significantly higher than that in the control group, but TBIL level in
      the CSC group was significantly lower than that in the control group (p<0.05).
      Linear correlation analysis showed that PLT was a risk factor for CSC, and TBIL
      was a protective factor for CSC. The sensitivity of PLT and TBIL in diagnosis of
      CSC was 75.2 and 72.7%, respectively, and the specificity of PLT and TBIL in
      diagnosis of CSC was 65.8 and 63.3%, respectively. PLT of CSC patients was
      significantly higher than that of the control group, and TBIL of CSC patients was
      significantly lower than that of the control group, but they both gradually
      reduced to normal levels after treatment, which can be regarded as the index for
      the clinical diagnosis of CSC in the future.

PMID- 30116340
TI  - miR-6852 serves as a prognostic biomarker in colorectal cancer and inhibits tumor
      growth and metastasis by targeting TCF7.
AB  - MicroRNAs (miRs) are have been demonstrated to serve important functions in the
      genesis of human cancer, including colorectal cancer (CRC). The role of miR-6852
      in CRC remains unknown. In this study, it was demonstrated that miR-6852 was
      underexpressed in CRC tissues compared with adjacent normal tissues. Moreover,
      the expression of miR-6852 was negatively correlated with CRC metastasis, whereas
      positively correlated with patient prognosis. It was revealed that the
      overexpression of miR-6852 significantly inhibited the proliferation and invasion
      of CRC cells. miR-6852 overexpression reduced CRC cells in the S phase. TCF7 was
      identified to be a direct target of miR-6852 in CRC cells. Overexpression of miR
      6852 significantly inhibited the mRNA and protein levels of TCF7 in CRC cells.
      Furthermore, TCF7 was highly expressed in CRC tissues and cell lines. TCF7
      expression was negatively correlated with miR-6852 levels in CRC tissues.
      Finally, knockdown of TCF7 significantly suppressed the proliferation and
      invasion of CRC cells. Taken together, the results of the present study indicated
      that miR-6852 serves as a tumor suppressor in CRC through targeting TCF7.

PMID- 30116341
TI  - Effects of probucol on atherosclerotic plaque and soluble thrombomodulin in
      patients with coronary heart disease.
AB  - This study explored the effects of probucol on atherosclerotic plaques and
      soluble thrombomodulin in patients with coronary heart disease (CHD). Five
      hundred and eighty-three patients with CHD who were admitted to Jining First
      People's Hospital from February 2013 to February 2014. A total of 300 of them
      received conventional treatment, and were assigned to the control group, while
      the remaining 283 patients were treated with probucol in addition to the
      conventional treatment, and were assigned to the observation group. A
      retrospective analysis was performed on the total cholesterol levels,
      atherosclerotic plaque sizes, and soluble thrombomodulin levels. Probucol was
      administered at a dose of 500 mg twice a day for a period of 16 weeks. The total
      cholesterol level decreased gradually over time during the treatment. After 8
      weeks of treatment, the total cholesterol level in the observation group was
      lower than that in the control group (P<0.05). After 8 weeks of treatment, the
      atherosclerotic plaque area in the observation group decreased compared with that
      before treatment (P<0.05). After 8 and 16 weeks of treatment, the plaque area in
      the observation group was smaller than that in the control group (P<0.05). The
      soluble thrombomodulin level at any time-point after treatment was lower than
      that before treatment in both groups (P<0.05). At the same time-point, the level
      in the observation group was lower than that in the control group (P<0.05). The
      total cholesterol and soluble thrombomodulin levels were positively correlated
      with the atherosclerotic plaque area (r=0.841, P=0.001; r=0.725, P=0.008). When
      patients with CHD were treated with probucol in addition to the conventional
      treatment, a reduction of the atherosclerotic plaque area, as well as a decrease
      of both the total cholesterol and soluble thrombomodulin levels, was observed.
      Overall, patients with CHD experienced improved symptoms following treatment with
      probucol.

PMID- 30116342
TI  - Therapeutic effect of vascular interventional therapy and aspirin combined with
      defibrase on cerebral ischemia in rats.
AB  - Therapeutic effect of vascular interventional therapy and aspirin combined with
      defibrase in the treatment of cerebral ischemia in rat model were investigated.
      Ninety rats were selected to establish cerebral ischemia model. Animal models
      were randomly divided into observation group and control group, with 45 rats in
      each group. Rats in observation group were treated with vascular intervention,
      and control group was treated with aspirin combined with defibrase. Peak systolic
      velocity (Vs) and end-diastolic velocity (Vd) were compared between two groups
      before and after 12 months of treatment. Therapeutic effects were compared before
      and after 6 months, and before and after 12 months of treatment. Vs and Vd of
      vascular lesions in observation group at 12 months were reduced after treatment,
      and were significantly lower than those in control group (p<0.05). After
      treatment, Vs and Vd in observation group were significantly reduced (p<0.05).
      There was no significant difference in Vs and Vd values between the groups before
      treatment (p>0.05). NDS scores in observation group were significantly lower than
      those in control group at 6 months and 1 year after treatment (p<0.05). There
      were no significant changes in NDS score at 6 and 12 months after treatment in
      control group compared with pretreatment group (p>0.05). NDS in observation group
      was significantly reduced at 6 and 12 months after treatment compared with
      pretreatment level (p<0.05). One year after treatment, incidence of cerebral
      infarction and transient ischemic attack and mortality in observation group were
      significantly lower than those in the control group (p<0.05). Intracranial
      vascular interventional therapy can achieve satisfactory outcomes in the
      treatment of cerebral ischemia, and can effectively promote nerve function
      recovery, and reduce the incidence of cerebrovascular diseases and mortality.

PMID- 30116343
TI  - Investigation of the values of CT perfusion imaging and ultrasound elastography
      in the diagnosis of liver fibrosis.
AB  - This study intended to investigate the clinical application values of computed
      tomography (CT) perfusion imaging and ultrasound elastography in the diagnosis of
      liver fibrosis, and to analyze the characteristics and diagnostic values of the
      two methods in liver fibrosis. A total of 320 patients diagnosed with suspected
      liver fibrosis in Qingdao Municipal Hospital from April 2014 to May 2016 were
      selected. The patients were diagnosed by ultrasound elastography and CT perfusion
      imaging, respectively, and the influencing characteristics and diagnostic
      accuracies of the two methods were compared. Among 320 patients, there were 315
      definitely diagnosed with liver fibrosis through liver biopsy. The accuracy of CT
      perfusion imaging was 95.63% (306/325), while that of ultrasound elastography was
      91.88% (294/320); there was a significant difference in accuracy between the two
      methods (P>0.05). CT perfusion imaging was superior to ultrasound elastography in
      the degree of liver fibrosis (P<0.05). Receiver operating characteristic (ROC)
      curve analysis showed that the areas under the curve (AUC) of patients were 0.841
      and 0.865 in S1 (P>0.05), 0.830 and 0.887 in S2 (P>0.05), 0.851 and 0.931 in S3
      (P>0.05), and 0.951 and 0.970 in S4, respectively (P>0.05). AUC values of ROC
      curves of CT perfusion imaging and ultrasound elastography in diagnosing liver
      fibrosis were 0.833 and 0.857, respectively (P>0.05). Both CT perfusion imaging
      and ultrasound elastography have relatively high accuracies in the clinical
      diagnosis of liver fibrosis, and they are worth promoting and applying. However,
      the best imaging method needs to be selected according to the actual situation of
      patients and research purpose.

PMID- 30116344
TI  - The diagnostic value of three-dimensional CT angiography for patients with acute
      coronary artery disease.
AB  - Computed tomography angiography (CTA) is an efficient method for the diagnosis of
      heart disease. However, few contemporary studies have evaluated the prognostic
      value of three-dimensional (3D)-CTA for patients with acute coronary artery
      disease. The aim of the present study was to investigate the diagnostic value of
      3D-CTA for patients with acute coronary artery disease. A total of 136 patients
      with suspected acute coronary artery disease were recruited and received
      conventional coronary angiography (CCA) and 3D-CTA. 3D-CTA was used to assess
      calcified plaques in the coronary arteries (CCTA), the ratio of calcified plaque
      volume to vessel circumference (RVTC) and diagnostic accuracy. The results
      revealed that 3D-CTA was a more effective diagnostic method for identifying
      calcified plaques in patients with acute coronary artery disease compared with
      CCA. 3D-CTA demonstrated a significantly better area under curve, sensitivity,
      specificity, positive predictive value and negative predictive value compared
      with CCA (P<0.01). In the present study, 3D-CTA was used to successfully diagnose
      86 patients with acute coronary artery disease, 34 with myocardial infarction and
      16 with stable angina. 3D-CTA images clearly showed global noise levels and
      target-to-background ratios determined by manually delineated coronary plaque
      lesions compared with CCA. Furthermore, 3D-CTA was significantly better for
      discriminating ischemia compared with CCA (P<0.01). In conclusion, the results of
      the present study suggest that 3D-CTA provides superior diagnostic performance
      compared with CCA alone in patients with acute coronary artery disease.

PMID- 30116345
TI  - Randomized controlled study on the curative effects of twist-drill craniotomy and
      burr-hole craniotomy in the treatment of chronic subdural hematoma.
AB  - The present randomized controlled study investigated the differences in the
      curative effects of twist-drill craniotomy (TDC) and burr-hole craniotomy (BHC)
      in the treatment of chronic subdural hematoma (CSDH). A total of 40 patients
      diagnosed with CSDH via head computed tomography (CT) who required surgical
      decompression from January 2016 to January 2017 were enrolled in the present
      study, and were randomly divided into a TDC group (n=20) and a BHC group (n=20).
      The modified Rankin scale (mRS) scores of patients were recorded prior to the
      operation, and at 48 h and 3 months after the operation. The differences in the
      mRS score (VmRS) among the groups were calculated using the Mann-Whitney U test.
      The 40 patients enrolled comprised 33 males and 7 females, and there were no
      significant differences in the general clinical characteristics between the two
      groups. In the BHC group, 3 patients had a pre-operative mRS score of 5 points,
      among which 2 cases died at 32 and 45 days after discharge. In the TDC group, 4
      patients had a pre-operative mRS score of 5 points, among which 1 case died of
      epilepsy and pulmonary infection at 1 month after the operation. No difference in
      the mortality rate was present between the two groups. During the 3-month follow
      up, head CT indicated that the intracranial hematoma in a total of 4 patients,
      including 3 cases in the TDC group and 1 case in the BHC group, completely
      disappeared. In the BHC group, 3 cases required a repeated incision and drainage
      after the first operation, while no secondary operation was required in any of
      the cases of the TDC group. The average length of stay at the hospital (LOS)
      after TDC was 9.00+/-2.91 days, which was significantly shorter than that after
      BHC (14.75+/-5.95 days). In the total sample of 40 patients, a longer LOS was
      associated with a higher risk of secondary operation due to recurrence after
      discharge. The variation value of the mRS score at 3 months after the operation
      and its ratio vs. the pre-operative score in the TDC group were significantly
      different from those in the BHC group, suggesting that the improvement of
      neurological function after TDC was significantly greater than that after BHC.
      Although 18 patients (90%) in the TDC group were cured, there was no significant
      difference from the cure rate in the BHC group [15 patients (75%)]. In
      conclusion, no significant differences were identified in the cure rate and the
      mortality rate of patients with CSDH after the two types of surgical treatment.
      However, the mRS score in the TDC group at 3 months after the operation exhibited
      a significantly greater improvement compared with that in the BHC group, and the
      overall LOS in the TDC group was significantly shorter than that in BHC group.
      Therefore, TDC is superior to BHC in the treatment of CSDH (trial registration
      no. ChiCTR-INR-16008368).

PMID- 30116346
TI  - CYSLTR1 promotes adenoid hypertrophy by activating ERK1/2.
AB  - Cysteinyl leukotriene receptor 1 (CYSLTR1) serves a pivotal role in allergic
      reactions, which is one of the main causes of adenoid hypertrophy. The present
      study aimed to investigate the function of CYSLT1 within adenoid hypertrophy. A
      total of 40 patients with adenoid hypertrophy were recruited between January 2014
      and January 2016 at the Children's Hospital of Hebei Province, China. The
      patients were divided into either the mild-moderate group or the severe group
      according to their disease severity. The expression of CYSLT1 in the adenoid
      tissue and whole blood of all patients and healthy controls was detected by
      reverse transcription-quantitative polymerase chain reaction. Associations
      between the expression level of CYSLT1 and the clinical characteristics of
      patients were analyzed. Primary human adenoid epithelial cells (HAECs) with
      CYSLT1 knockdown and overexpression were constructed. The levels of extracellular
      signal-regulated kinase (ERK)2 and phosphorylated-ERK1/2 in adenoid tissue and
      HAECs were detected by western blot analysis. The expression of CYSLT1 in adenoid
      tissue and whole blood of all patients with adenoid hypertrophy was significantly
      higher compared with the healthy controls (P<0.05). In addition, the expression
      level of CYSLT1 was significantly higher in the severe group compared with the
      mild-moderate group (P<0.05). The highest level of p-ERK1/2 in adenoid tissue was
      observed in the severe group, followed by the mild-moderate group and then the
      control group (P<0.05). CYSLT1 expression was positively associated with the
      severity of disease. CYSLT1 knockdown significantly decreased the level of p
      ERK1/2 in HAECs (P<0.05), while CYSLT1 overexpression significantly increased the
      level of p-ERK1/2. It was concluded that CYSLT1 may contribute to the progression
      of adenoid hypertrophy by activating ERK1/2.

PMID- 30116347
TI  - Psychiatric side effects of pegylated interferon-alpha and ribavirin therapy in
      Iranian patients with chronic hepatitis C: A meta-analysis.
AB  - An estimated 185 million people worldwide are infected with hepatitis C virus
      (HCV). Combination therapy with pegylated interferon-alpha (peg IFN) and
      ribavirin is the first line of treatment against the psychiatric side effects,
      including mood disorders, anxiety and irritability. In the present study, all of
      the studies electronically published between 2000 and 2016 were retrieved using
      databases including Scopus, PubMed, Institute for Scientific Information, Science
      Direct and Google Scholar. All of the articles were independently evaluated by
      two reviewers and the results were compared, followed by removal of duplicate,
      irrelevant and re-published studies after reviewing. The studies were assessed
      based on the heterogeneity of their results using the Cochrane test and I2
      analysis. All groups included neuropsychiatric side effects, fatigue was reported
      at the highest rate in 60.41% [95% confidence interval (CI)=39.18-81.64%] and
      insomnia was reported at a lower rate in 16.28% of cases (95% CI=6.59-25.98%). In
      conclusion, the present meta-analysis indicated that treatment with peg IFN +
      ribavirin or interferon only is associated with a wide range of neuropsychiatric
      side effects, including fatigue, mood disorders, anxiety, irritability, emotional
      ability and agitation.

PMID- 30116348
TI  - Efficacy and safety of long-course tacrolimus treatment for idiopathic membranous
      nephropathy.
AB  - The aim of the present study was to observe the efficacy and safety of long
      course treatment with tacrolimus combined with low-dose corticosteroids for
      idiopathic membranous nephropathy (IMN). A total of 76 patients with IMN
      diagnosed by renal biopsy between March 2012 and January 2016 form The First
      People's Hospital of Changzhou (Changzhou, China) were selected and randomly
      divided into a short-course group and a long-course group (each, n=38). Patients
      in the short-course group were treated with hormone combined with tacrolimus for
      12 months, whereas those in the long-course group received the same treatment for
      24 months. The efficacy, safety and recurrence of the two groups of patients were
      observed, and serum ALB, urine protein, Scr and blood glucose were assessed once
      a month for 24 months by measuring blood biochemistry. A total of 11 patients
      exhibited adverse effects, 6 of whom were serious and as such were excluded from
      the study. In the short-course group, 8 of 35 patients demonstrated complete
      remission (CR), 17 patients exhibited partial remission (PR) and the remaining 10
      patients had no remission (NR); however the disease recurred in 8 patients
      following treatment. In the long-course group, 16 of 35 patients exhibited CR, 14
      patients demonstrated PR and the remaining 5 patients had NR. Furthermore, the
      disease recurred in 4 patients following treatment. Significant differences were
      observed in urine protein and serum ALB at 18 and 24 months following treatment
      between the two groups while Scr and blood glucose had no significant differences
      at any time point. It was concluded that long-course tacrolimus combined with low
      dose hormone effectively treats idiopathic membranous nephropathy and that
      therapy demonstrated a relatively high remission rate, and the recurrence rate of
      the disease is low.

PMID- 30116349
TI  - Metformin exerts anti-inflammatory effects on mouse colon smooth muscle cells in
      vitro.
AB  - Inflammatory bowel disease (IBD) is a chronic incurable condition characterized
      by relapsing inflammation of the gut. Intestinal smooth muscle cells (SMCs) are
      affected structurally and functionally during IBD due to excessive production of
      different inflammatory mediators. Metformin is a widely used antidiabetic agent
      known to exert several anti-inflammatory effects in different tissues
      independently from its hypoglycemic effect. The aim of the present study was to
      investigate the effect of metformin on expression and secretion of different
      cytokines and chemokines from mouse colon SMCs (CSMCs) following induction of
      inflammation with lipopolysaccharide (LPS) in vitro. CSMCs from male BALB/c mice
      were isolated and cultured in Dulbecco's modified Eagle's medium and treated with
      LPS (1 ug/ml) and 0, 5, 10 or 20 mM metformin for 24 h. Expression and secretion
      of tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha),
      macrophage colony stimulating factor (M-CSF), T cell activation gene-3 (TCA-3)
      and stromal cell-derived factor-1 (SDF-1) was evaluated by ELISA. LPS-treated
      CSMCs demonstrated significantly increased expression of TNF-alpha, IL-1alpha, M
      CSF, TCA-3 and SDF-1 when compared with the control group (P<0.05). Co-treatment
      with metformin (5 and 10 mM) significantly reduced their expression by ~20-40%
      when compared with LPS treatment alone (P<0.05). Furthermore, secretion of TNF
      alpha, IL-1alpha, M-CSF and TCA-3 into the conditioned media was significantly
      decreased by metformin (5 and 10 mM; P<0.05). In addition, metformin decreased
      levels of LPS-induced nuclear factor-kappaB phosphorylation. These data suggest
      that metformin may provide beneficial anti-inflammatory effects on CSMCs and it
      may be utilized as an adjunct therapy for patients suffering from IBD.

PMID- 30116350
TI  - Decreased microRNA-140-5p contributes to respiratory syncytial virus disease
      through targeting Toll-like receptor 4.
AB  - The abnormal expression of miRNAs (miRs) has previously been reported in
      respiratory syncytial virus (RSV) disease. However, to the best of our knowledge,
      the expression of miR-140-5p in patients with an RSV infection has never been
      explored. Reverse transcription-quantitative polymerase chain reaction was
      performed to analyze the level of miR-140-5p in the blood and nasopharyngeal
      airway samples. ELISAs were performed to determine the levels of tumor necrosis
      factor alpha, interleukin (IL)-1beta, IL-6 and IL-8. A dual luciferase reporter
      assay was also performed to investigate the possible target gene of miR-140-5p.
      The results demonstrated that the levels of miR-140-5p were significantly
      decreased in the nasal mucosal and peripheral blood samples of patients with RSV
      infection. It was also revealed that overexpression of miR-140-5p decreased the
      inflammatory responses, while inhibition of miR-140-5p enhanced the inflammatory
      responses. Additionally, three binding sites of miR-140-5p in the 3untranslated
      region (UTR) of Toll-like receptor (TLR)4 were identified and a dual luciferase
      reporter assay demonstrated that miR-140-5p significantly suppressed the relative
      luciferase activity of pmirGLO-TLR4-3UTR. Furthermore, the level of miR-140-5p
      was shown to be increased following interferon (IFN)alpha incubation. Notably,
      inhibition of miR-140-5p markedly attenuated IFNalpha-mediated downregulation of
      tumor necrosis factor alpha, and interleukin-1beta, -6 and -8 in BEAS-2B cells.
      In summary, decreased miR-140-5p levels are involved in RSV-infection diseases
      primarily through targeting TLR4.

PMID- 30116351
TI  - MicroRNA-302 inhibits cell migration and invasion in cervical cancer by targeting
      DCUN1D1.
AB  - MicroRNA serve crucial roles in a variety of human cancer types. The miR-302-367
      cluster has been reported to suppress the proliferation of cervical carcinoma
      cells through the novel target AKT1; however, the molecular mechanism of miR-302
      in cervical cancer metastasis remains unclear. The present study aimed to
      investigate the clinical significance of miR-302-3p expression in cervical
      cancer, and to examine the regulatory mechanism of miR-302-3p in the malignant
      phenotypes of cervical cancer cells. The present data indicated that miR-302-3p
      was significantly downregulated in cervical cancer tissues compared with the
      level in adjacent non-tumor tissues, and low expression of miR-302-3p was
      significantly associated with node metastasis, advanced clinical stage, and poor
      prognosis in patients with cervical cancer. Restoration of miR-302-3p expression
      caused a significant reduction in cervical cancer cell migration and invasion.
      Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was identified as
      a novel target gene of miR-302-3p, and miR-302-3p negatively regulated the mRNA
      and protein expression of DCUN1D1 in cervical cancer HeLa cells. Additionally,
      overexpression of DCUN1D1 rescued the effects of miR-302-3p on the migration and
      invasion of cervical cancer cells. Furthermore, DCUN1D1 was upregulated in
      cervical cancer tissues compared with the levels in adjacent tissues, and its
      high expression was associated with node metastasis, advanced clinical stage, and
      shorter survival time in patients with cervical cancer. Notably, a negative
      correlation between miR-302-3p and DCUN1D1 expression in cervical cancer tissues
      was observed. Taken together, the present study suggests that miR-302-3p serves a
      suppressive role in cervical cancer metastasis, partly at least, via directly
      targeting DCUN1D1. Therefore, miR-302-3p/DCUN1D1 may be a potential therapeutic
      target for cervical cancer treatment.

PMID- 30116352
TI  - Gene subtype analysis of Treponema pallidum for drug resistance to azithromycin.
AB  - Azithromycin has been widely used for the treatment of Treponema pallidum.
      However, the drug resistance of T. pallidum for azithromycin is currently
      increasing. The aim of the present study was to analyze the association between
      gene subtypes of T. pallidum and drug resistance for azithromycin. The gene
      subtypes of T. pallidum were assayed by a polymerase chain reaction technique.
      Drug resistance of T. pallidum was analyzed using an antimicrobial susceptibility
      test. The results demonstrated that gene type tpr presented higher drug
      resistance compared with arp and tp0548 gene types of T. pallidum. Gene type tpr
      was identified as eight gene subtypes (14a/f, 14e/f, 12e/f, 12d/f, 6d/f, 11d/f,
      14j/f and 8d/f) among 324 cases. It was identified that 23S rRNA A2058G mutation
      was observed in gene subtypes 14a/f, 14e/f and 12e/f. A2059G mutation occurred in
      the gene subtypes 8d/f, 12d/f, 6d/f, 11d/f and 14j/f. The proportions of
      azithromycin-resistant genotypes harboring either the A2058G or the A2059G
      mutation among the T. pallidum strains were 34.2 and 65.8%, respectively. The
      antimicrobial susceptibility test demonstrated that A2059G mutations exhibited a
      higher drug resistance for azithromycin compared with A2058G mutations. In
      conclusion, these results indicate that azithromycin resistance in T. pallidum is
      associated with gene subtype, which may contribute to the treatment of T.
      pallidum.

PMID- 30116353
TI  - Inflammatory cytokines and cells are potential markers for patients with cerebral
      apoplexy in intensive care unit.
AB  - Cerebral apoplexy is a disease caused by obstruction of the blood circulation in
      the brain. Evidence has indicated that inflammatory cytokines are implicated in
      ischaemic cerebral apoplexy and are regarded as a general cardiovascular risk
      factor, which may be a possible immediate trigger, a component of the response to
      tissue injury and a therapeutic target. The present study investigated changes of
      inflammatory cytokines and cells in patients with cerebral apoplexy at the
      intensive care unit (ICU). The plasma concentrations of inflammatory cytokines,
      including tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, IL-6, IL-8, IL
      10, IL-1beta and IL-17A were evaluated using ELISA. Changes in the plasma
      concentrations of inflammatory cells were detected by using flow cytometry. The
      results indicated that serum levels of TNF-alpha, IL-4, IL-8, IL-1beta and IL-17A
      were upregulated in patients with cerebral apoplexy compared with those in
      healthy individuals, while those of IL-6 and IL-10 were downregulated.
      Furthermore, it was demonstrated that the plasma concentration of lymphocytes,
      granulocytes and mononuclear cells was decreased in patients with cerebral
      apoplexy in the ICU compared with that in healthy individuals. Of note, humoral
      as well as cellular inflammatory cytokines were evidently increased in patients
      with cerebral apoplexy in ICU. In conclusion, the present study provided evidence
      that inflammatory cytokines and inflammatory cells are upregulated, while anti
      inflammatory cytokines are downregulated in patients with cerebral apoplexy in an
      ICU setting. These results suggest that anti-inflammatory interventions may be
      beneficial either in the prevention or acute treatment of patients with cerebral
      apoplexy.

PMID- 30116354
TI  - TTB2 induces apoptosis in Ewing sarcoma cells.
AB  - A steroidal saponin named pennogenin 3-O-alpha-L-rhamnopyranosyl-(1->2) [alpha-L
      rhamnopyranosyl-(1->4)]-beta-D-glucoyranoside(TTB2) has been successfully
      separated from the n-BuOH extracts of Trillium tschonoskii Maxim and is able to
      induce cytotoxicity to some types cancer cells. The present study aimed to
      investigate how this novel saponinin duces cytotoxicity in malignant sarcoma
      cells and to clarify its molecular mechanisms of action. It was determined this
      steroidal saponin induced the apoptosis in Rh1 cells and activated caspase-3 and
      caspase-9. Additionally, it disrupted the mitochondrial membrane potential and
      altered the expression of bax and bcl-2. Thus, the results of present study
      identified that an anticancer saponin isolated from Trillium tschonoskii Maxim
      may be developed as a potential novel therapeutic strategy to treat certain types
      of cancer, including lung cancer and lung sarcoma.

PMID- 30116355
TI  - Grazoprevir/elbasvir treatment for the relapse of HCV genotype 1b infection after
      ledipasvir/sofosbuvir: A case report.
AB  - The treatment of chronic hepatitis C has radically changed due to the development
      of direct-acting antiviral agents (DAAs). Twelve-week treatment with ledipasvir
      and sofosbuvir (LDV/SOF), a combination of DAAs, is highly effective in patients
      with hepatitis C virus (HCV) genotype 1 infection. However, the overall sustained
      virological response rate 12 weeks after the end of treatment (SVR12) is not
      100%. Elbasvir (EBR) combined with grazoprevir (GZR) is the latest approved
      therapy for patients with genotype 1 or 4 chronic hepatitis C. However, to the
      best of our knowledge no case reports have described retreatment with GZR/EBR in
      patients with a history of failed LDV/SOF treatment. The present case report
      indicated a case in which GZR/EBR was effective for the retreatment of a patient
      with a history of failed LDV/SOF treatment and chronic hepatitis C. The present
      study indicated a 55-year-old Japanese male with a history of chronic hepatitis C
      and compensated liver cirrhosis. The patient exhibited the amino acid mutation
      Y93H in NS5A. Therefore, treatment with LDV/SOF was initiated, which was
      effective and suppressed the virus during oral administration. However, 4 weeks
      after treatment, the patient's viral load relapsed and returned to its original
      level. After the patient provided informed consent, treatment with GZR/EBR was
      initiated. No problems related to GZR/EBR were observed during treatment and the
      patient's SVR12 was evaluated at 12 weeks posttreatment. In conclusion, GZR/EBR
      treatment was useful for treating a relapse of HCV genotype 1b infection in the
      present case after LDV/SOF treatment, despite liver fibrosis, in the presence of
      the high-frequency amino acid mutation Y93H in NS5A. Although it will be
      necessary to examine a large number of cases, the present findings suggest that
      GZR/EBR may be a potential treatment option for relapse of HCV genotype 1b
      infection after LDV/SOF treatment.

PMID- 30116356
TI  - Value of serum Mycoplasma pneumoniae immunoglobulin in the diagnosis of
      mycoplasma-related pneumonia in newborns.
AB  - [This retracts the article DOI: 10.3892/etm.2017.4654.].

PMID- 30116358
TI  - Natural killer cells inhibit metastasis of ovarian carcinoma cells and show
      therapeutic effects in a murine model of ovarian cancer.
AB  - Ovarian cancer has the highest mortality rate and is the most common of all
      gynecologic malignancies. Novel treatments for ovarian cancer are urgently
      required to improve outcomes and the overall survival of patients. The present
      study investigated whether immunotherapy with natural killer (NK) cells affected
      the survival of mice with ovarian cancer. Results analysis identified adjunctive
      NK cells as a potential therapeutic method in ovarian cancer. Patient-derived
      ovarian cells were isolated, cultured and subsequently injected subcutaneously
      into immune deficient BALB/c-nude mice. Human NK cells were isolated from
      peripheral blood mononuclear cells and cultured for expansion in vitro. The
      present results demonstrated that ovarian cells in BALB/c-nude mice did not
      induce spontaneous ovarian cancer cell metastasis in the NK-treated group. In
      addition, NK cells activated immune cells in the immune system, which resulted in
      inhibition of ovarian tumor growth in vitro and in a murine xenograft model of
      ovarian cancer. The data also indicated that cytotoxic activity of NK cells
      prevented migration and invasion of ovarian cancer cells, which contributed to
      prevention of systemic metastasis and suggested that NK cells could be effective
      cells for therapy against ovarian cancer. Furthermore, NK cells induced apoptosis
      and increased the number of cluster of differentiation (CD)4+, CD8+ as well as
      cytotoxic T lymphocyte responses by intravenous injection in a murine xenograft
      model of ovarian cancer. These results suggested that NK cells inhibited the
      systemic metastasis for ovarian cancer cells. In conclusion, the present study
      suggested that NK cell immunotherapy inhibited systemic metastasis of ovarian
      cancer cells and improved the survival rate of mice. Sufficient supplementation
      of NK cells may serve as a promising immunotherapeutic strategy for ovarian
      cancer.

PMID- 30116357
TI  - Endometriosis and in vitro fertilisation.
AB  - The aim of the present review was to discuss a matter of concern in the clinical
      field of obstetrics/gynecology, namely the potency of in vitro fertilization
      (IVF) in the management of endometriosis-associated infertility. Endometriosis is
      a medical condition affecting one tenth of women in their fertile years, and
      accounts for up to 50% of infertile women. Thus, such high prevalence has
      established the necessity for investigating the effectiveness of available
      techniques in eradicating the disease and constraining infertility as well as the
      accompanying pain symptoms of endometriosis. The underlying mechanisms connecting
      endometriosis with low fecundity have been extensively studied, both in terms of
      genetic alterations and epigenetic events that contribute to the manifestation of
      an infertility phenotype in women with the disease. Several studies have dealt
      with the impact of IVF in pregnancy rates (PRs) on patients with endometriosis,
      particularly regarding women who wish to conceive. Results retrieved from studies
      and meta-analyses depict a diverse pattern of IVF success, underlining the
      involvement of individual parameters in the configuration of the final outcome.
      The ultimate decision on undergoing IVF treatment should be based on objective
      criteria and clinicians' experience, customized according to patients' individual
      needs.

PMID- 30116359
TI  - Effects of ginsenoside Rb1 on oxidative stress injury in rat spinal cords by
      regulating the eNOS/Nrf2/HO-1 signaling pathway.
AB  - The present study aimed to investigate whether ginsenoside Rb1 (G-Rb1) attenuates
      spinal cord injury-associated oxidative stress in rats by regulating the
      endothelial nitric oxide synthase eNOS/nuclear factor erythroid 2-related factor
      2 (Nrf2)/heme oxygenase (HO)-1 signaling pathway. Sprague Dawley rats were
      randomly divided into the sham operation group (S group), spinal cord injury
      group (SCI group), G-Rb1 treatment group (G-Rb1 group) and SCI+G-Rb1+Inhibitor L
      name group (L-name group). The posterior limb function was evaluated via the
      Basso, Beattie and Bresnahan scoring method. The levels of superoxide dismutase
      (SOD), malondialdehyde (MDA), catalase (CAT) and glutathione (GSH) in serum were
      measured by ELISA. The pathological changes in the spinal cord were observed by
      H&E staining. Reverse transcription-quantitative polymerase chain reaction and
      western blot analyses were used to detect eNOS, phosphorylated (p)-eNOS, heat
      shock protein (HSP)90, Nrf2 and NAD(P)H quinone dehydrogenase 1 (Nqo1) at the
      mRNA and protein level. Immunohistochemistry was used to detect the expression of
      Nrf2 and p-eNOS. Compared with the S group, the scores of spinal cord function in
      the SCI group were significantly lower, and the levels of MDA were significantly
      increased, while the levels of SOD, CAT and GSH protein in spinal cord were
      significantly decreased (P<0.05). The spinal cord tissue exhibited hemorrhage,
      neuronal degeneration/necrosis, as well as mononuclear cell and lymphocyte
      infiltration. The eNOS, HSP90, Nrf2, Nqo1 and HO-1 mRNA levels were decreased
      (P<0.05). Compared with those in the SCI group, the spinal cord function score in
      the G-Rb1 group were significantly higher and the serum MDA content was
      significantly decreased, while the activity of SOD, CAT and GSH was significantly
      increased (P<0.05). The degeneration/necrosis of spinal cord neurons was
      attenuated, inflammatory cell infiltration was significantly reduced and the
      levels of eNOS, HSP90, Nrf2, Nqo1 and HO-1 were significantly upregulated
      (P<0.05). In the group that was administered the eNOS inhibitor L-name, the
      levels of eNOS, HSP90, Nrf2, Nqo1 and HO-1 were significantly decreased. In
      conclusion, G-Rb1 attenuates oxidative stress in injured spinal cords. The
      mechanism may at least in part involve the eNOS/Nrf2/HO-1 pathway.

PMID- 30116360
TI  - 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D-glucoside attenuates methionine and
      choline-deficient diet-induced non-alcoholic fatty liver disease.
AB  - Previous studies have suggested that 2,3,5,4'-tetrahydroxy-stilbene-2-O-beta-D
      glucoside (TSG) prevents progression of non-alcoholic fatty liver disease (NAFLD)
      induced by high-fat diet. The present study aimed to evaluate whether TSG could
      reverse NAFLD induced by a methionine and choline-deficient (MCD) diet and
      identify the possible mechanism of action. C57BL6/J mice were fed a MCD diet and
      were treated with TSG, fenofibrate, and resveratrol for 9 weeks. Regulatory
      effects of several cytokines and enzymes, including Nod-like receptor protein 3,
      apoptosis-associated speck-like protein containing a C-terminal caspase
      recruitment domain (ASC), caspase-1, interleukin (IL)-18, IL-1beta, and gut
      microbiota balance were investigated. TSG significantly reduced NAFLD biochemical
      indexes, including total cholesterol, triglyceride, low density lipoprotein
      cholesterol, very low density lipoprotein cholesterol, aspartate aminotransferase
      and free fatty acid. Middle dosage (TSG.M, 35 mg/kg) of TSG reduced the
      expression of ASC and caspase-1. Furthermore, TSG displayed gut microbiota
      regulatory effects on MCD-induced NAFLD mice. The results of the present study
      suggested that TSG prevented the occurrence and development of MCD diet-induced
      NAFLD. The data further indicated that TSG may serve as a promising lead compound
      that may aid with intervention in NAFLD therapy.

PMID- 30116361
TI  - Antitumor effects of carbon nanotube-drug complex against human breast cancer
      cells.
AB  - To improve the bio-solubility and sustained-release properties of a carbon
      nanotube (CNT)-drug complex, the present study used a hydrophilic polymer,
      polyethylene glycol (PEG), and beta-estradiol (E2), which targets the estrogen
      receptor in human breast cancer cells (HBCCs), to modify CNTs carrying lobaplatin
      (LBP) to form E2-PEG-CNT-LBP. The in vitro inhibitory effects against HBCCs and
      the in vivo pharmacological effect of the complex on heart, liver and kidney
      tissues were also evaluated. The results indicated that the inhibitory effects of
      this complex against HBCCs reached 80.44% within 72 h. A blood biochemical test
      of normal mice indicated that this complex reduced platelet counts, while
      aspartate aminotransferase levels were increased compared with those in the
      control group. Histopathological analysis revealed no obvious adverse effects on
      the heart, liver and kidneys. The in vivo results indicated that the novel E2-PEG
      CNT-LBP complex had no obvious toxic effects while exhibiting sustained-release
      properties. The clearance of E2-PEG-CNT-LBP by non-specific uptake systems was
      delayed and its clearance was increased compared with LBP alone.

PMID- 30116363
TI  - Effects of dexmedetomidine as an adjunct in transversus abdominis plane block
      during gynecological laparoscopy.
AB  - Ultrasound-guided transversus abdominis plane (TAP) block for abdominal surgery
      has been widely studied in clinical settings. However, dexmedetomidine as an
      adjunctive analgesic combined with TAP block has been rarely reported. The
      present study evaluated the efficacy of TAP block combined with dexmedetomidine
      adjunct for gynecological laparoscopy. In brief, 90 patients were randomly
      divided into three groups: Group I, which received post-operative intravenous
      analgesia only after general anesthesia; Group II, which received a TAP block
      with 20 ml 0.375% ropivacaine; and Group III, which received a TAP block with 20
      ml of 0.375% ropivacaine and 1 ug/kg dexmedetomidine after induction. In all
      groups, propofol was used for general anesthesia. The dosage of propofol,
      duration of the operation, and the time of awakening, spontaneous breathing and
      extubation were recorded. In addition, the Steward and visual analogue scale
      (VAS) scores were determined at 2, 4, 8, 12 and 24 h post-surgery. The occurrence
      of nausea and vomiting and/or respiratory depression was also recorded. Compared
      with those in Group I, the dosage of propofol, as well as the time of awakening,
      spontaneous breathing and extubation were significantly decreased in Group III
      (P<0.01 and P<0.05, respectively). In addition, the VAS score at 2 and 4 h in
      Group II (both P<0.05) and 2, 4 (both P<0.01) and 8 h (P<0.05) in Group III after
      the surgery were significantly lower compared with those in Group I. Furthermore,
      in Groups II and III, a lower number of cases experienced nausea and vomiting
      (P<0.05). In conclusion, the ultrasound-guided TAP block combined with
      dexmedetomidine adjunct may improve recovery from anesthesia and reduce post
      operative pain (trial registration no. ChiCTR-IPR-15007398).

PMID- 30116362
TI  - Analysis of the miRNA and mRNA involved in osteogenesis of adipose-derived
      mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are bone marrow stromal cells capable of
      differentiating into different tissue types. Osteoblastic differentiation is a
      complex process that is critical for bone formation. An increasing number of
      studies have suggested that microRNAs (miRNAs) may serve important roles in
      various biological processes, including osteogenesis of MSCs. However, less is
      known about the participation of particular miRNAs in the osteogenic
      differentiation of adipose-derived stem cells (ADSCs). In order to identify
      functional miRNAs and the key genes involved in the osteogenesis of MSCs, the
      present study reconstructed a global network using data from the National Center
      for Biotechnology Information Gene Expression Omnibus. Meanwhile, gene ontology
      and pathway analysis were performed using the Cytoscape plug-in BinGO and the
      Database for Annotation, Visualization, and Integration Discovery, respectively.
      An miRNA-mRNA network composed of 72 mRNA and nine miRNA nodes advised by
      bioinformatics analysis was constructed. These mRNAs and miRNAs were predicted to
      be involved in the regulation of osteogenic differentiation of ADSCs according to
      the gene microarray. In the present study, six miRNAs (miR-143-3p, miR-135a-5p,
      miR-31-5p, miR-22-3p, miR-193b-3p and let-7i-5p) were observed to be highly
      associated with the osteogenesis of ADSCs, and dihydropyrimidinase like 3 was
      identified as a novel regulator in this process. These results provide support
      for further investigations into the management of bone regeneration-associated
      diseases.

PMID- 30116364
TI  - Effect of NMDA on proliferation and apoptosis in hippocampal neural stem cells
      treated with MK-801.
AB  - The purpose of the present study was to investigate effects of N-methyl-D
      aspartate (NMDA) on proliferation and apoptosis of hippocampal neural stem cells
      (NSCs) treated with dizocilpine (MK-801). Cultures of hippocampal NSCs were
      randomly divided into four groups consisting of an untreated control, cells
      treated with MK-801, NMDA and a combination of MK801 and NMDA (M+N).
      Proliferative and apoptotic responses for each of the experimental groups were
      determined by MTS and flow cytometry. The results revealed that MK-801 and NMDA
      exerted significant effects on hippocampal NSCs proliferation. Cell survival
      rates decreased in MK-801, NMDA and M+N treated groups compared with the control
      group. Cells survival rates in NMDA and M+N treated groups increased compared
      with the MK-801 treated group. MK-801 and NMDA were demonstrated to significantly
      affect apoptosis in hippocampal NSCs. Total and early stages of apoptosis in MK
      801 and NMDA groups significantly increased compared with the control group.
      Total and early apoptosis of NSCs in the M+N group significantly decreased
      compared with MK-801 and NMDA groups. Late apoptosis of NSCs in MK-801 and NMDA
      groups significantly decreased compared with the control group. Late apoptosis of
      NSCs in the M+N group significantly increased compared with MK-801 and NMDA
      groups. The present study revealed that MK-801 inhibited proliferation and
      increased apoptosis in hippocampal NSCs. NMDA may reduce the neurotoxicity
      induced by MK-801, which may be associated with its activity towards NMDA
      receptors and may describe a novel therapeutic target for the treatment of
      schizophrenia.

PMID- 30116365
TI  - Effect of lanthanum chloride on tumor growth and apoptosis in human ovarian
      cancer cells and xenograft animal models.
AB  - Ovarian cancer is the leading cause of mortality resulting from gynecologic
      cancer. A common anti-ovarian tumor drug is cisplatin; however, repeated use of
      cisplatin causes severe resistance and leads to poor long-term survival rate in
      ovarian cancer patients. Recently, it was reported that lanthanum chloride
      (LaCl3) may inhibit tumor growth and induce apoptosis in certain cancer cells. In
      the present study, the effect of LaCl3 on ovarian cancer was determined in vivo
      and in vitro. A cisplatin-sensitive human ovarian cancer cell line, COC1, was
      used in the current study. A xenograft animal model of ovarian cancer was
      established injecting COC1 or cisplatin-resistant COC1 cells (COC1/DDP) cells
      into mice. A TUNEL assay was used to determine the apoptosis of the COC1 or
      COC1/DDP cells and a immunohistochemical assay was conducted to measure the
      expression of B-cell lymphoma-2, Ki67, breast cancer 1 (BRCA)1, BRCA2 and
      excision repair cross-complementation group 1 in COC1 or COC1/DDP cells. It was
      observed that LaCl3 promoted apoptosis in COC1 and COC1/DDP cells. In addition,
      LaCl3 plus cisplatin led to further increase in the expression levels of tumor
      suppressor genes and decrease in the expression of oncogenes. Furthermore,
      application of LaCl3 and cisplatin inhibited tumor growth in vivo in a xenograft
      animal model. These results indicated the synergistic role of LaCl3 on cisplatin
      induced inhibition of cancer cell proliferation and tumor growth, providing a
      potential and effective candidate for the treatment of ovarian tumors.

PMID- 30116366
TI  - Correlation between the levels of serum cystatin C and substance P in peripheral
      blood in diabetes mellitus patients complicated with hypertension.
AB  - Correlation between the serum cystatin C and substance P in peripheral blood of
      diabetes mellitus patients complicated with hypertension was investigated.
      Diabetes mellitus patients with or without hypertension were selected in No. 215
      Hospital of Shaanxi Nuclear Industry from December 2015 to February 2017. There
      were 60 patients with only hypertension (hypertension control group), 60 patients
      with only diabetes mellitus (diabetes mellitus control group) and 60 patients
      with diabetes mellitus combined with hypertension (observation group). Levels of
      serum cystatin C and substance P in peripheral blood were measured via
      immunoturbidimetry and enzyme-linked immunosorbent assay, respectively, and the
      correlation with hypertension was analyzed. The average level of serum cystatin C
      in the observation group was higher than that of the two control groups (P<0.05).
      The level of substance P in peripheral blood of the observation group was lower
      than that of the diabetic control group (P<0.05). The levels of serum cystatin C
      in patients with grade III hypertension in observation group were higher than
      those in grades II and I, and the levels of substance P in peripheral blood of
      patients with grade III hypertension in observation group were lower than those
      in grades II and I. Systolic pressure of patients in observation group was
      significantly positively correlated with level of serum cystatin C, but
      significantly negatively correlated with level of substance P in peripheral blood
      (P<0.05). Compared with the diabetes mellitus patients, level of serum cystatin C
      was higher, and level of substance P peripheral blood was lower in diabetes
      mellitus patients complicated with hypertension. In diabetes mellitus patients,
      blood pressure was positively correlated with serum cystatin C level, and
      negatively correlated with substance P level in peripheral blood.

PMID- 30116367
TI  - BMP14 induces tenogenic differentiation of bone marrow mesenchymal stem cells in
      vitro.
AB  - Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells, which have the
      capacity to differentiate into various types of mesenchymal cell phenotypes,
      including osteoblasts, chondroblasts, myoblasts and tendon fibroblasts (TFs). The
      molecular mechanism for tenogenic differentiation of BMSCs is still unknown. The
      present study investigated the effects of bone morphogenetic protein (BMP) 14 on
      BMSC differentiation in vitro. It was revealed that BMP14 significantly increased
      the expression of tendon markers (scleraxis and tenomodulin) at the mRNA and
      protein level, which led to the upregulation of sirtuin 1 (Sirt1) expression. The
      gain or loss of Sirt1 function may promote or inhibit tenogenic differentiation
      by deacetylating the peroxisome proliferator-activated receptor (PPAR)-gamma.
      BMP14 also triggered the phosphorylation of c-Jun N-terminal kinase (JNK) and
      Smad1; overexpression of Sirt1 significantly increased the phosphorylation and
      knockdown of Sirt1 significantly decreased the phosphorylation. The inhibition of
      JNK and Smad significantly increased the acetylation of PPARgamma and inhibited
      the expression of tenogenic differentiation markers. These results suggest that
      BMP14 may induce the tenogenic differentiation of BMSCs via the Sirt1-JNK/Smad1
      PPARgamma signaling pathway. The present study provided a cellular and molecular
      basis for the development of novel therapeutic strategies for tendon healing.

PMID- 30116369
TI  - Hydroxybutyrate promotes the recovery from cerebral infarction by activating Amp
      activated protein kinase signaling.
AB  - Recent studies have shown that hydroxybutyrate (GHB) is effective for protection
      against ischemia/brain damage in rat models. However, the specific underlying
      mechanism is poorly understood. In line with the previous studies, the present
      data showed that GHB improves cerebral blood flow (CBF) and physiological
      variables, including pH, pCO2 and pO2. Using CD31-immunofluorescence staining, a
      reduction of blood vessel density was indicated in the middle cerebral artery
      occlusion (MCAO) group; however, GHB treatment enhanced the cerebral vascular
      density in the ischemic area. In addition, GHB treatment increased the number of
      BrdU/lectin double-positive cells. Furthermore, the reduction of nestin-positive
      cells was identified in the brain of MCAO rats, while the number of nestin
      positive cells was significantly increased after GHB administration. Compared
      with the sham group, the activation of Amp-activated protein kinase (AMPK) was
      identified in MCAO rats, suggesting stress-mediated AMPK activation after
      ischemia. Furthermore, the western blot assay showed that GHB treatment resulted
      in further activation of AMPK and endothelial nitric oxide synthase (eNOS),
      suggesting an enhanced energy supply. In summary, the present novel data
      indicates that GHB promotes the recovery from cerebral infarction mainly by
      activating AMPK and eNOS signaling, thereby enhancing angiogenesis and neuron
      regeneration.

PMID- 30116368
TI  - Combination of bevacizumab and photodynamic therapy vs. bevacizumab monotherapy
      for the treatment of wet age-related macular degeneration: A meta-analysis of
      randomized controlled trials.
AB  - The purpose of this meta-analysis was to compare the efficacy and safety of the
      combination of bevacizumab and photodynamic therapy (PDT) with bevacizumab
      monotherapy for the treatment of age-related macular degeneration (AMD). Patients
      with active choroidal neovascularization (CNV) secondary to AMD were included in
      the present study. The treatment group included patients treated with a
      combination of bevacizumab and PDT and patients treated with bevacizumab
      monotherapy. Only randomized controlled trials (RCTs) were included in the
      analysis. The PubMed, EMBASE and Cochrane Central Register of Controlled Trials
      databases were searched. Meta-analysis was performed using RevMan v.5.3 software,
      and best-corrected visual acuity (BCVA), central retinal thickness (CRT) and the
      average number of bevacizumab retreatments were assessed. A total of 5 RCTs were
      included in the analysis. There were no significant differences observed in the
      mean BCVA change between the combination treatment group and the bevacizumab
      monotherapy group [standard mean difference 0.20; 95% confidence interval (CI) 
      0.53, 0.93, P=0.59]. There were also no significant differences in the CRT
      increases between the two groups [weighted mean difference (WMD) -22.16, 95% CI 
      52.01 to 7.69, P=0.15]. No significant differences were observed in the
      proportions of patients gaining >15 letters between the two groups [risk ratio
      (RR) 0.86, 95% CI 0.64, 1.15, P=0.30]. However, the average number of the
      ranibizumab retreatments was significantly lower in the combination treatment
      group compared with the bevacizumab monotherapy group (WMD, -2.70, 95% CI -3.93
      to -1.46; P<0.0001). Additionally, there were no significant differences in the
      rate of ocular adverse events (RR, 0.57; 95% CI, 0.27 to 1.22; P=0.15) and
      systemic adverse events (RR, 5.42; 95% CI, 0.29 to 101.77; P=0.26) between the
      two groups. In conclusion there were no significant differences in mean BCVA
      change, CRT increases, the proportions of patients gaining >15 letters, or the
      incidences of ocular adverse events and systemic adverse events. However,
      combination treatment may significantly reduce the average number of bevacizumab
      retreatments compared with monotherapy.

PMID- 30116370
TI  - The application of conventional us and transthoracic ultrasound elastography in
      evaluating peripheral pulmonary lesions.
AB  - The aim of the present study was to evaluate the diagnostic value of ultrasound
      (US) elastography in differentiating between benign and malignant peripheral lung
      lesions (PLLs). This retrospective study included 91 consecutive patients with 91
      PLLs. Conventional US, strain elastography (SE), acoustic radiation force impulse
      imaging (ARFIimaging) and point share wave elastography (p-SWE) were performed.
      All of the pathological results were confirmed by US-guided biopsies or
      surgeries. There were 36 benign PLLs and 55 malignant PLLs on pathology. For
      conventional US, a lesion diameter >=5 cm, irregular contour, presence of air
      bronchogram and non-abundant vascularity were predictive factors of malignancy
      (P<0.05). SE scores were observed to be invalid in differentiating between
      malignant and benign PLLs (P=0.542). For ARFIimaging scores, an elasticity score
      of 3 or greater was predictive of malignancy, with a sensitivity of 83.6% (46/55)
      and a specificity of 52.8% (19/36). For p-SWE, the share wave velocity of
      malignant PLLs was higher than benign ones (2.47+/-0.92 vs. 1.85+/-0.92 m/sec;
      P=0.0022). When 1.951 m/sec was selected as the cut-off value, a sensitivity of
      70.9% (39/55) and a specificity of 69.4% (25/36) were obtained. Thus, US,
      particularly US elastography, is helpful in distinguishing malignant PLLs from
      benign PLLs.

PMID- 30116371
TI  - Impact of timing of initiation of dialysis on long-term prognosis of patients
      undergoing hemodialysis.
AB  - There are a lot of controversies pertaining to correctness of timing for the
      initiation of dialysis in chronic kidney disease (CKD) patients. The present
      study was conducted to examine the potential association of initiation timing of
      dialyses with long-term prognosis in CKD patients. In total, 294 patients
      confirmed as end-stage renal disease (ESRD) were included as study subjects.
      According to the estimated glomerular filtration rate (eGFR) at initiation time,
      the patients were classified into four groups based on eGFR: >=10.5, 8-10.4, 6-8
      and <6 ml/min * (1.73 m2)-1. The primary outcomes were defined by all-cause
      mortality. The median eGFR of the 294 patients at initiation time was 5.43 (2.27
      13.92) ml/min * (1.73 m2)-1. The patients with lower eGFR at the start of
      hemodialysis had a higher proportion of Charlson comorbidity index (CCI) scores
      of 0-2 and had lower hematocrit. The multivariate Cox regression analysis
      indicated that CCI, cerebrovascular diseases and chronic obstructive pulmonary
      disease were significantly associated with all-cause mortality, but not eGFR at
      the dialysis initiation. Furthermore, stratified analyses confirmed elevated eGFR
      that had no advantage on long-term prognosis. The present findings have shown
      that the prevalence of anemia, hyperuricemia and calcium and phosphorus
      metabolism disorders of patients with low eGFRs at the initiation of hemodialysis
      was higher in comparison to the patients with high eGFRs. Therefore, the long
      term prognosis of patients with high eGFRs prior to hemodialysis was not
      improved.

PMID- 30116373
TI  - MicroRNA-423-5p inhibits colon cancer growth by promoting caspase-dependent
      apoptosis.
AB  - Plasma microRNA (miR)-423-5p is a potential biomarker for the detection of colon
      cancer. However, the expression and biological role of miR-423-5p in colon
      tumorigenesis remains unclear. In the current study, reverse transcription
      quantitative polymerase chain reaction was used to determine miR-423-5p
      expression in malignant colon tissues and plasma from patients with colon cancer.
      Cell viability, colony formation and apoptosis assays, as well as western
      blotting, were performed to investigate the biological role and regulatory
      mechanisms of miR-423-5p in colon cancer. The results demonstrated that miR-423
      5p expression was downregulated in tumor tissues and plasma from patients with
      colon cancer, as well as in colon cancer cell lines. Furthermore, overexpression
      of miR-423-5p promoted colon cancer cell apoptosis and resulted in the inhibition
      of cell proliferation and colony formation. Mechanistically, miR-423-5p induced
      the expression of caspases 3, 8 and 9, as well as p53 in colon cancer. The effect
      of z-VAD treatment indicated that the miR-423-5p-mediated colon cancer cell
      apoptosis is caspase-dependent. These results suggest that miR-423-5p is a tumor
      suppressor in colon cancer and a potential diagnostic target to enable the early
      detection of colon cancer.

PMID- 30116372
TI  - Application of a novel targeting nanoparticle contrast agent combined with
      magnetic resonance imaging in the diagnosis of intraductal papillary mucinous
      neoplasm.
AB  - Intraductal papillary mucinous neoplasm (IPMN) is a severe disease with
      macroscopic visible mucin secretion that primarily occurs in biliary tracts or
      pancreatic ducts. In comparison with standard diagnostic imaging, probing the
      molecular abnormalities associated with the initial stages of diseases rather
      than imaging the end effects markedly improves the accuracy of diagnosis. In the
      present study, magnetic resonance imaging (MRI) in combination with the contrast
      agent PEGylated magnetoliposome consisting of gadolinium ethoxybenzyl
      diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) and target molecules of IPMN
      were investigated in the diagnosis of patients with suspected IPMN. The present
      investigation indicated that the novel targeting nanoparticle contrast agent
      targeted platelet-derived growth factor receptor-beta and RET, and maintained a
      high affinity with tumor markers located on the IPMN surface. The novel targeting
      nanoparticle contrast agent combined with MRI exhibited increased sensitivity in
      diagnosing early-stage patients with IPMN. Furthermore, image quality was
      improved following the use of the novel targeting nanoparticle contrast agent
      combined with MRI compared with standard MRI. The targeting nanoparticle contrast
      agent retained sufficient affinity and was present for an adequate amount of time
      to observe the tumor mass in papillae using MRI. Notably, the targeting
      nanoparticle contrast agent was metabolized at 12 h post-injection. In
      conclusion, these outcomes indicate that the novel targeting nanoparticle
      contrast agent combined with MRI improved image quality and sensitivity compared
      with standard MRI, which suggests that this approach may be promising for
      clinical detection in patients with suspected IPMN.

PMID- 30116374
TI  - MicroRNA-379 suppresses cell proliferation, migration and invasion in
      nasopharyngeal carcinoma by targeting tumor protein D52.
AB  - MicroRNAs (miRs) have been demonstrated to be important regulators of malignant
      behavior in nasopharyngeal carcinoma (NPC) tumorigenesis. The present study aimed
      to investigate the biological roles and underlying mechanisms of miR-379 in NPC.
      The study initially observed that miR-379 was significantly downregulated in NPC
      clinical tissues and cell lines using reverse transcription-quantitative
      polymerase chain reaction (RT-qPCR). Next, gain-of-function assays were performed
      on human the NPC cell lines, C666-1 and 5-8F, including MTT, colony formation and
      transwell migration assays. The results indicated that ectopic expression of miR
      379 suppressed the NPC cell proliferation, colony formation, migration and
      invasion in vitro. In addition, tumor protein D52 (TPD52) was identified as a
      direct target of miR-379 by a dual-luciferase reporter assay, while
      overexpression of miR-379 markedly reduced TPD52 expression at the mRNA and
      protein levels, as determined by RT-qPCR and western blot analysis, respectively.
      Furthermore, silencing of TPD52 significantly inhibited the C666-1 cell
      proliferation, migration and invasion. These findings suggest that miR-379
      negatively regulates the growth and migration of NPC cells by downregulating
      TPD52 expression, while modulation of miR-379 expression may be a therapeutic
      strategy for NPC.

PMID- 30116376
TI  - Laminin-chitosan-PLGA conduit co-transplanted with Schwann and neural stem cells
      to repair the injured recurrent laryngeal nerve.
AB  - The aim of the present study was to assess the possibility and efficacy of
      utilizing a laminin-chitosan-poly (lactic-co-glycolic acid), otherwise known as
      laminin-chitosan-PLGA, nerve conduit with the co-transplantation of Schwann and
      neural stem cells to repair peripheral nerve defects. Previous in vitro
      experiments have demonstrated that the three-dimensional structure of the built
      in fiber filament electrospinning of laminin-chitosan-PLGA nerve conduit is
      beneficial to the migration and regeneration of nerve cells, and has notable
      mechanical strength and plasticity. It is able to provide support in the neural
      tissue regeneration process, and has the ability to degrade itself once
      peripheral nerves complete their regeneration, providing more advantages than
      other biological and synthetic materials. In the present study, 132 female
      Sprague Dawley rats were used to establish an animal model of laryngeal nerve
      injury, and the rats were randomly divided into six groups for experimentation.
      The nerve conduit was prepared and co-cultured with Schwann and neural stem
      cells, and micro-surgical techniques were used to repair the 5-mm-long recurrent
      laryngeal nerve injuries. Functional and histological assessments were performed
      at 8 and 12 weeks post-surgery, respectively. The results revealed that the
      laminin-chitosan-PLGA nerve conduit combined with Schwann and neural stem cells
      was able to promote nerve regeneration (P<0.05), and its effect was superior to
      those of the autograft (P<0.05). The results of the present study suggest that
      this is the ideal method for repairing peripheral nerve defects, and cells in the
      graft may promote nerve regeneration.

PMID- 30116377
TI  - Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells.
AB  - Curcumin is a natural compound that appears to be promising for clinical
      application, as it has been shown in in vitro and in vivo studies to exert
      antitumor effects by modulating multiple signaling cellular pathways. In the
      present study, the antitumor effects of curcumin and its mechanism of action were
      investigated in cultured breast cancer cells. The MTT assay was used to determine
      the effect of curcumin on breast cancer cell proliferation, flow cytometry was
      used to detect alterations of the cell cycle, and western blot analysis was used
      to determine the expression of signaling molecules involved in the cell cycle,
      proliferation and apoptosis. The results revealed that curcumin significantly
      inhibited the proliferation of various breast cancer cell lines, such as T47D,
      MCF7, MDA-MB-231 and MDA-MB-468, with an IC50 at the micromolar level, indicating
      the potent antitumor activity of curcumin. In-depth study of its mechanism of
      action revealed that curcumin induced cell cycle arrest at the G2/M phase and
      decreased the expression of the CDC25 and CDC2 proteins, while increasing the
      expression of P21. In addition, curcumin inhibited the phosphorylation of protein
      kinase B (Akt)/mammalian target of rapamycin (mTOR), decreased B-cell lymphoma 2
      (BCL2) and promoted BCL-2-associated X protein (BAX) and cleavage of caspase 3,
      subsequently inducing apoptosis of breast cancer cells. In conclusion, curcumin
      inhibited the proliferation of breast cancer cells and induced G2/M phase cell
      cycle arrest and apoptosis, which may be associated with the decrease of CDC25
      and CDC2 and increase of P21 protein levels, as well as inhibition of the
      phosphorylation of Akt/mTOR and induction of the mitochondrial apoptotic pathway.
      The findings of the present study may provide a basis for the further study of
      curcumin in the treatment of breast cancer.

PMID- 30116375
TI  - Premature senescence activation in DLD-1 colorectal cancer cells through adjuvant
      therapy to induce a miRNA profile modulating cellular death.
AB  - Cancer, and particularly colon cancer, is associated with an increasing number of
      cases resistant to chemotherapy. One approach to overcome this, and to improve
      the prognosis and outcome of patients, is the use of adjuvant therapy alongside
      the standard chemotherapy regiment. In the present study, the effect of deuterium
      depleted water (DDW) as a potential modulator of adjuvant therapy on DLD-1
      colorectal cancer models was assessed. A number of functionality assays were
      performed, including MTT, apoptosis and autophagy, and mitochondrial activity and
      senescence assays, in addition to assessing the capacity to modify the pattern of
      released miRNA via microarray technology. No significant effect on cell viability
      was identified, but an increase in mitochondrial activity and a weak pro
      apoptotic effect were observed in the treated DLD-1 cells cultured in DDW
      prepared medium compared with those grown in standard conditions (SC).
      Furthermore, the findings revealed the capacity of DDW medium to promote
      senescence to a higher degree compared with SC. The exosome-released miRNA
      pattern was significantly modified for the cells maintained in DDW compared with
      those maintained in SC. These findings suggest that DDW may serve as an adjuvant
      treatment; however, a better understanding of the underlying molecular mechanism
      of action will be useful for developing novel and efficient therapeutic
      strategies, in which the transcriptomic pattern serves an important role.

PMID- 30116378
TI  - Protective effects of honokiol against oxidative stress-induced apoptotic
      signaling in mouse podocytes treated with H2O2.
AB  - Honokiol (HNK), an important bioactive compound purified from Magnolia
      officinalis Cortex, has been demonstrated to have manifold beneficial anti
      oxidative, anti-inflammatory, anti-bacterial and antitumor pharmacological
      effects. In the present study, the association of HNK in the signaling mechanism
      associated with hydrogen peroxide (H2O2)-induced apoptosis of cultured mouse
      podocytes was investigated. HNK did not cause significant changes in podocyte
      viability when its concentration remained below 20 uM. MTS assay and flow
      cytometry confirmed that H2O2 significantly enhanced the rates of apoptosis while
      produce significant reduction in viability of podocytes. Following 24 h of pre
      treatment with different concentrations of HNK, the viability of adherent
      podocytes increased and apoptosis significantly decreased in a dose-dependent
      manner below 20 uM. Reverse transcription-polymerase chain reaction and western
      blot results indicated that HNK significantly decreased the expression of mRNA
      and cleaved protein of caspase-3 and caspase-9 in podocytes pre-treated with
      H2O2. Furthermore, phosphorylation of the signaling molecules protein kinase B
      (Akt) and extracellular signal-regulated kinase (Erk) 1/2 appeared to increase
      following HNK treatment. In conclusion, HNK largely eliminated the role of
      promoting podocyte apoptosis in an oxidative stress environment, which was a
      protective factor on podocytes cultured with H2O2. The anti-oxidative stress
      mechanisms of HNK are partly due to suppressing the expression of caspase-3 and
      caspase-9 and upregulating phosphorylated-Akt and -Erk 1/2.

PMID- 30116379
TI  - The preparation and clinical application of diagnostic DNA microarray for the
      detection of pathogens in intracranial bacterial and fungal infections.
AB  - The present study prepared 2 types of DNA diagnostic chips based on 16S ribosomal
      DNA (rDNA) and 18S-28S rDNA, and evaluated their values in the detection of
      pathogens in intracranial bacterial/fungal infections. A total of 14 probes of
      bacteria (Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa,
      Escherichia coli, Haemophilus influenza, Stenotrophomonas maltophilia, Neisseria
      meningitidis, Enterobacter spp., Enterococcus faecalis, Enterococcus faecium,
      Listeria monocytogenes, Staphylococcus aureus, Streptococcus pneumonia and
      coagulase negative staphylococcus) and 4 probes of fungi (Candida albicans,
      Candida tropicalis, Candida glabrata and Cryptococcus neoformans), determined
      frequently in cerebrospinal fluid (CSF), were designed and used for preparation
      of microarrays. CSF samples from 88 patients with clinically suspected
      intracranial infection and standard strains were used to evaluate the chips. The
      same samples were also analyzed by culture and sequencing. The results
      demonstrated that the sensitivity, specificity and false-positive rate of the
      microarray assay compared with culture method were 100 vs. 68.3% (P<0.05), 97.1
      vs. 100%, and 2.9 vs. 0%, respectively. The minimum concentration of detection
      with the chips was 10 cfu ml-1 for bacteria and 100 cfu ml-1 for fungi. The
      specificity of the probes was confirmed, and no cross-reaction was detected in
      the present study. Furthermore, 13 cases were positive in the microarray and
      negative in culture. However, 4 cases were not identified as clear pathogens and
      only positive in the 16S probe sites. The diagnostic DNA microarray for
      intracranial infections has proven to be more rapid and sensitive, and it may be
      a better option for clinical application than culture methods.

PMID- 30116380
TI  - MicroRNA-663 regulates the proliferation of fibroblasts in hypertrophic scars via
      transforming growth factor-beta1.
AB  - The present study determined the expression of microRNA (miR)-663 in hypertrophic
      scar (HS) tissues and investigate the regulatory mechanisms of miR-663 in HS. A
      total of 51 patients diagnosed with HS between December 2013 and February 2016
      were included in the present study. HS tissues (experimental group) and HS
      adjacent tissues (control group) were collected. Primary fibroblasts were
      obtained from HS tissue and transfected with small-interfering RNA against
      transforming growth factor (TGF)-beta1 or miR-663 mimics. Reverse-transcription
      quantitative PCR was used to determine the levels of TGF-beta1 mRNA and miR-663.
      Western blot analysis was performed to determine TGF-beta1 protein expression. An
      MTT assay was employed to detect the proliferation of fibroblasts, and a dual
      luciferase reporter assay was performed to identify the binding of miR-663 with
      TGF-beta1 mRNA. TGF-beta1 was found to have a regulatory role in HS at the
      transcriptional level. The expression of TGF-beta1 was upregulated in HS tissues,
      and knockdown of TGF-beta1 in cultured fibroblasts led to inhibition of
      proliferation. The expression of miR-663 was downregulated in HS. miR-663 was
      revealed to regulate the expression of TGF-beta1 by binding with the 3'
      untranslated region of TGF-beta1 mRNA. Elevated expression of miR-663 inhibited
      the proliferation of fibroblasts by regulating TGF-beta1 expression. The present
      study demonstrated that upregulation of TGF-beta1 in HS tissues is associated
      with the downregulation of miR-663 expression. miR-663 may regulate the
      proliferation of fibroblasts in HS and the expression of associated proteins.

PMID- 30116381
TI  - Trimetazidine combined with berberine on endothelial function of patients with
      coronary heart disease combined with primary hypertension.
AB  - Effects of trimetazidine combined with berberine on endothelial function of
      patients with coronary heart disease combined with primary hypertension (CCP)
      were investigated. A total of 68 patients with CCP were selected from July 2014
      to August 2016 to serve as observation group. At the same time, 68 healthy people
      were also selected to serve as control group (physiological saline). Expression
      of endothelial nitric oxide synthase (eNOS) mRNA in the blood samples of the
      observation and control groups before and after treatment was determined by RT
      PCR. Levels of NO in the plasma of the observation and control groups before and
      after treatment were measured by nitric acid reductase method. Brachial artery
      flow-mediated vasodilation (FMD) of observation and control groups was detected
      by brachial artery ultrasonography before and after treatment. Before treatment,
      expression level of eNOS mRNA in blood of the observation group was significantly
      lower than that of the control group (P<0.05). After treatment, expression level
      of eNOS mRNA was significantly increased (P<0.05). Plasma NO content 41.06+/-3.63
      mol/l in blood of the observation group was significantly lower than that of the
      control group 53.28+/-3.09 mol/l (P<0.05). After treatment with trimetazidine and
      berberine, level of NO 50.75+/-2.75 mol/l was significantly increased compared
      with the level before treatment (P<0.05). FMD value (5.03+/-0.95) was
      significantly lower in observation group than that in control group (16.04+/
      1.63) (P<0.05). After treatment with trimetazidine and berberine, FMD value
      (14.02+/-2.39) was significantly increased compared with the level before
      treatment (P<0.05). The results suggested that the combination of trimetazidine
      and berberine can increase the content of NO in blood and promote endothelium
      dependent dilation function of brachial arteries, which is helpful in the
      treatment of CCP.

PMID- 30116382
TI  - Clinical study of the use of gastroscopy as oral choledochoscopy.
AB  - Clinical value and safety of the use of gastroscopy as oral choledochoscopy in
      the treatment of biliary diseases was explored. Clinical data of 55 patients with
      biliary diseases who underwent gastroscopy were retrospectively analyzed. The
      types of gastroscopy, size of duodenal papilla incision, balloon dilatation, the
      success rate of gastroscopy entry, depth of gastroscopy entering into bile duct,
      endoscopic diagnosis and postoperative complications were recorded. Simple
      insertion-by-hand was performed, and insertion into common bile duct was
      successfully achieved in 53 cases, and the overall technical success rate was
      96.4%. Residual bile duct stones in 25 patients (45.5%) after endoscopic
      retrograde cholangio-pancreatography (ERCP) were removed through endoscopy. Nine
      cases of benign stenosis and 2 cases of malignant stenosis were confirmed as
      'cholangiocarcinoma' or 'duodenal papilla well-differentiated adenocarcinoma' by
      biopsy. Balloon oppression under intraoperative endoscopy was performed for 2
      cases (3.6%) with biliary hemorrhage, and argon ion coagulation was successfully
      performed. No obvious abnormalities were found in 13 cases (23.6%) through
      gastroscopic biliary exploration. Complications occurred in 15 patients with a
      complication rate of 27.3%, including 2 cases of cholecystitis (3.6%), 8 cases of
      amyloidosis (14.6%) and 4 cases of acute pancreatitis (7.3%), and all those
      complications were cured. One case (1.8%) had perforation of biliary tract and
      was discharged after conservative treatment. The use of gastroscopy as oral
      choledochoscopy is safe as effective. However, this technique causes some rare
      and serious complications. Therefore, further studies are needed to improve this
      technique.

PMID- 30116383
TI  - Effects of graft preconditioning on gamma-irradiated deep frozen tendon
      allografts used in anterior cruciate ligament reconstruction.
AB  - Preconditioning of the grafts prior to implantation into the knee is considered
      to reduce the loss of tension caused by graft viscoelasticity after anterior
      cruciate ligament reconstruction. The present study analyzed the impacts of
      different preconditioning forces on the biomechanical properties of the gamma
      irradiated deep frozen tendon allografts. A total of 36 tendon grafts were
      randomly divided into three groups and were preconditioned at 80 N (group 1), 160
      N (group 2) and 320 N (group 3) for 10 min. Subsequently, the grafts were
      gradually completely relaxed for 1 min and subsequently received 25 cyclic loads
      of 0-80 N. Afterwards, the grafts were loaded to 80 N, which was maintained for
      30 min. Finally, load was gradually increased until ultimate failure at maximum
      load (UFML) was obtained. There were significant differences in the stiffness and
      UFML values between the 3 groups (all P<0.05). The graft stiffness in group 3
      significantly increased compared with the other 2 groups, and the stiffness of
      group 2 grafts increased compared with group 1. The UFML in group 3 was
      significantly lower compared with groups 1 and 2, while there was no significant
      difference between groups 1 and 2. In the present study, the results suggested
      that increasing the initial tension could effectively reduce the loss of
      stiffness due to viscoelasticity for the gamma-irradiated deep frozen allogeneic
      tendon grafts. However, overloaded initial tension decreased the tensile
      strength.

PMID- 30116384
TI  - Personalized genomic analysis based on circulating tumor cells of extra-skeletal
      Ewing sarcoma of the uterus: A case report of a 16-year-old Korean female.
AB  - A 16-year-old female with Ewing sarcoma, a very rare disease with poor prognosis
      in women, was admitted to the hospital with abdominal pain. Diagnostic laparotomy
      revealed the Ewing sarcoma originating from the extramural uterus. Histological
      examination yielded positive test results for CD99, vimentin, S-100, eosin 5
      maleimide and periodic acid-Shiff. EWS-FLI1 type 1 translocation was confirmed.
      Fibroblast growth factor receptor (FGFR) 4 (c.1162G> A) and HRas proto-oncogene
      (HRAS; c.182A> G) mutations were also detected. At eight months following
      complete remission, pelvic lymph node metastasis was confirmed. Epithelial cell
      adhesion molecule-positive circulating tumor cells (CTCs) were detected in liquid
      biopsy. FGFR3 (c.1948A> G) and FGFR4 (c.1162G> A) mutations were found in the
      CTCs. FGFR4 (c.1162G> A) and HRAS (c.182A> G) mutations were confirmed in cell
      free circulating tumor DNA. A sequence of EWSR1 gene was also confirmed in the
      CTCs. To the best of our knowledge, this is the first report of skeletal Ewing
      sarcoma being detected using multiple noninvasive diagnostic methods to observe
      genetic translocation and mutation in blood CTCs. It may be used to monitor the
      therapeutic effect of cancer or predict prognosis. Therefore, liquid biopsy is
      expected to serve a pivotal role in ultra-precise medicine in the future.

PMID- 30116385
TI  - Fluvastatin inhibits cardiomyocyte apoptosis after myocardial infarction through
      Toll pathway.
AB  - The present study intended to investigate the effect of fluvastatin on
      cardiomyocyte apoptosis after myocardial infarction in rats. Eighty myocardial
      infarction rat models were established and randomly divided into 4 groups (n=20):
      experimental group (n=20) was given fluvastatin treatment; sham operation group
      (n=20) and normal control group (n=20) were given saline. The dose of fluvastatin
      was 20 mg/(kg.d), and irrigation gavage was given for 1 week. Western blot
      analysis and reverse transcription-quantitative PCR (RT-qPCR) were used to detect
      the expression of TLR4 mRNA and protein in cardiomyocytes. TUNEL method was used
      to detect the apoptosis of cardiomyocytes. After fluvastatin treatment for 1
      week, RT-qPCR found that compared with myocardial infarction group, the TLR4 mRNA
      expression of fluvastatin treatment group and normal control group was
      significantly increased, and the differences between groups were a statistically
      significant difference (P<0.05). Western blot analysis showed that compared with
      the myocardial infarction group, the expression of TLR4 protein in normal control
      group, sham operation group and fluvastatin treatment group were significantly
      decreased, and they all were statistically significant (P<0.05). TUNEL method
      found that compared with the myocardial infarction group, the fluvastatin
      treatment group could significantly reduce the apoptosis of cardiomyocytes
      (19.2+/-3.8%), and the difference was statistically significant (P<0.05).
      Fluvastatin can inhibit myocardial infarction and decrease cardiomyocyte
      apoptosis by increasing the expression of TLR4-like receptor.

PMID- 30116386
TI  - Application of Ilizarov transverse tibial bone transport and microcirculation
      reconstruction in the treatment of chronic ischemic diseases in lower limbs.
AB  - The aim of the present study is to investigate the clinical value of Ilizarov
      transverse tibial bone transport and microcirculation reconstruction in the
      treatment of chronic ischemic diseases in lower limbs. A total of 90 patients
      with chronic ischemic diseases in lower limbs were selected and randomly divided
      into two groups: The observation group (n=45) and the control group (n=45). Those
      patients were treated with Ilizarov transverse tibial bone transport and
      microcirculation reconstruction, and percutaneous balloon angioplasty (PTBA),
      respectively. Changes in the diameter, blood flow of lower limb arteries in the
      paretic side, wound healing time, disappearance time of pains, dorsal foot skin
      temperature, and the expression area of vascular endothelial growth factors
      (VEGFs) were detected in both groups. Compared with control group, the diameters
      and blood flows of lower limb arteries were significantly larger (P<0.05), and
      the dorsal foot skin temperature was significantly higher at 1 day, 1 week and 1
      month after operation, respectively. Meantime, the expression area of VEGFs in
      the observation group was significantly larger than that in the control group at
      1 day, 1 week and 1 month, respectively. Furthermore, compared with control
      group, wound healing time and disappearance time of pains of patients were
      earlier in the observation group (P<0.05). At 1 month after operation, the
      intermittent claudication, rest pain and lower limb ulcer or gangrene among
      clinical symptoms of patients in the observation group improved significantly
      more than those in the control group (P<0.05). In conclusion, the application of
      Ilizarov transverse tibial bone transport and microcirculation reconstruction
      could achieve better outcomes in the treatment of chronic ischemic diseases in
      lower limbs.

PMID- 30116387
TI  - Protective effect of electro-acupuncture on liver ischemia-reperfusion injury in
      rats.
AB  - Liver ischemia-reperfusion injury is an important clinical complication in which
      excessive inflammation is a key factor; however, few studies have provided
      effective means of its regulation. As previous studies suggested that electro
      acupuncture (EA) is able control excessive inflammation, the present study aimed
      to explore its effects on liver ischemia-reperfusion injury in experimental rats.
      The animals were randomly divided into surgery and sham groups, which were
      further divided into four sub-groups, including a non-treatment (NT), a non-point
      acupuncture (NPA), the non-selective nicotinic acetylcholine receptor (AChR)
      agonist 1,1-dimethyl-4-phenyl L-pioperazinium iodide (DMPPI) and an EA group. The
      alanine aminotransferase (ALT), serum cytokine and myeloperoxidase (MP) levels
      and the tissue pathology were evaluated after 90 min of ischemia followed by a 4,
      8 or 24 h reperfusion. The results demonstrated that EA and DMPPI suppressed
      serum ALT elevation at 4 and 8 h reperfusion, whereas NPA did not. I/R induced
      hepatocellular necrosis, and cytoplasmic vacuolization and sinusoidal congestion
      was ameliorated by EA treatment after an 8 and 24 h reperfusion. In addition, EA
      also inhibited liver neutrophil accumulation, evidenced by a decreased MPO level
      at 8 h reperfusion. EA also suppressed the release of serum inflammatory factors
      TNF-alpha and IL-6 for the duration of reperfusion. However, little influence on
      IL-10 was observed. Mechanistically, vagus block by subphrenic vagotomy or
      mecamylamine hydrochloride abolished EA effect on liver damage, neutrophil
      accumulation and inflammatory factor release. In conclusion, it was demonstrated
      that EA protects the liver against I/R induced injury by inhibiting the
      inflammatory response, which is associated with the vagus.

PMID- 30116388
TI  - Treatment of severe periodontic-endodontic combined lesions with minocycline
      hydrochloride ointment combined with mineral trioxide aggregate.
AB  - Periodontic-endodontic combined lesions affect the quality of life of patients.
      The present study aimed to explore a way to achieve maximal effect in treating
      periodontic-endodontic combined lesions by using a combination of minocycline
      hydrochloride ointment (MHO) and mineral trioxide aggregate (MTA). In the present
      study, 294 patients were randomly divided into four groups: Control group, MHO
      group, MTA group and combination group. Endodontic and periodontic therapy was
      applied simultaneously on the anterior and posterior teeth of patients, and
      patient characteristics, gingival index (GI) and probing depth (PD) were noted
      when the patients were treated with the different strategies. Reexamination was
      performed 4 weeks after treatment and follow-up was performed 2 years later. The
      present study demonstrated that medical history, root filling and periapical
      condition within the patients were deemed as key factors in determining the
      success of treatment of periodontic-endodontic combined lesions. The effect of
      the combination treatment significantly exceeded that of either treatment alone
      (P<0.05). In addition, the teeth were significantly improved for patients with
      pathological types I, II and III in the combination group compared with either
      treatment group alone (P<0.05). Furthermore, compared with the MTA and MHO groups
      alone, the combination group demonstrated a significant decrease in PD and GI in
      severe periodontic-endodontic combined lesions. In conclusion, the present
      findings implied that combination treatment is significantly superior to single
      treatments applied to patients with severe periodontic-endodontic combined
      lesions.

PMID- 30116389
TI  - Fibroblast growth factor-21 is a potential diagnostic factor for patients with
      gestational diabetes mellitus.
AB  - Gestational diabetes mellitus (GDM) is a metabolic disease with symptoms of
      hyperglycemia, insulin resistance and fetal maldevelopment. Evidence has
      indicated that fibroblast growth factor (FGF)-21 is a multifunctional protein and
      exhibits potential therapeutic value for metabolic diseases. The present study
      investigated the diagnostic value of FGF-21 serum levels in patients with GDM
      (n=50) and age-matched healthy individuals (n=50). It was demonstrated that the
      gene and protein expression levels of FGF-21 were downregulated in adipose cells
      in patients with GDM compared with those in healthy individuals. The results also
      indicated that the serum levels of FGF-21 were downregulated in patients with GDM
      compared with those in healthy individuals. In addition, it was demonstrated that
      blood glucose and blood pressure were higher in patients with GDM compared with
      those in healthy individuals. GDM patients had a markedly higher insulin
      resistance and glucose tolerance than healthy individuals. However, GDM patients
      had significantly lower serum levels of insulin than healthy individuals. It was
      observed that the serum levels of FGF-21 were positively correlated with those of
      glucose in GDM patients. In conclusion, these results indicate that decreased FGF
      21 levels are associated with the risk of GDM, suggesting that FGF-21 may be a
      potential diagnostic factor for GDM.

PMID- 30116390
TI  - SIRT5 regulates pancreatic beta-cell proliferation and insulin secretion in type
      2 diabetes.
AB  - Impaired insulin secretion and insulin resistance are the primary characteristics
      of type 2 diabetes (T2D). However, the mechanisms underlying insulin secretion
      failure have yet to be elucidated. The present study demonstrated that sirtuin 5
      (SIRT5) is upregulated in patients with T2D and in pancreatic beta-cell lines. It
      was also revealed that elevated SIRT5 expression is positively associated with
      age and blood glucose levels, and negatively associated with pancreatic and
      duodenal homeobox 1 (PDX1) expression. Colony formation and Cell Counting Kit-8
      assays demonstrated that SIRT5 suppressed the proliferation of pancreatic beta
      cells in vitro. In addition, downregulation of SIRT5 promoted the secretion of
      insulin. Additionally, SIRT5 ectopic expression downregulated the expression of
      PDX1 and the inhibition of SIRT5 upregulated PDX1 expression. Chromatin
      immunoprecipitation assay analysis demonstrated that SIRT5 may regulate the
      transcription of PDX1 via H4K16 deacetylation. In conclusion, the results of the
      present study indicate that SIRT5 may serve an important role in the pathogenesis
      of T2D, and may present a novel therapeutic target for the treatment of patients
      with T2D.

PMID- 30116391
TI  - Propofol attenuates mast cell degranulation via inhibiting the miR
      221/PI3K/Akt/Ca2+ pathway.
AB  - The aim of the present study was to investigate the effect of propofol on
      immunoglobulin (Ig)E-activated mast cell degranulation and explore the underlying
      mechanisms responsible. RBL-2H3 cells were treated with propofol for at a variety
      of concentrations and different amounts of time. Cell viability was assessed
      using an MTT assay and microRNA (miR)-221 expression was quantified using reverse
      transcription-quantitative polymerase chain reaction. RBL-2H3 cells were
      transfected with miR-221 mimic or a negative control and degranulation, including
      the release of beta-hexosaminidase and histamine, was evaluated using an ELISA
      kit. The effect of miR-221 overexpression on the phosphorylation of protein
      kinase B (Akt) was detected using western blotting and extracellular Ca2+ influx
      was measured via afura-2 assay. The phosphoinositide 3-kinase(PI3K) inhibitor
      LY294002 was used to investigate the association between PI3K/Akt signaling and
      Ca2+ influx in the presence of propofol. The results demonstrated that propofol
      treatment suppressed RBL-2H3 cell proliferation in a dose- and time-dependent
      manner. Propofol inhibited miR-221 expression in a dose-dependent manner compared
      with the control group; however, the inhibitive effect was significantly
      abrogated following transfection with miR-221 mimics. Furthermore, beta
      hexosaminidase and histamine release, PI3K/Akt signaling and Ca2+ influx were
      decreased following propofol application. miR-221 overexpression markedly
      ameliorated the suppressive effect of propofol. Treatment with LY294002 reversed
      the propofol-induced decrement of Ca2+ influx on IgE-mediated RBL-2H3 cells,
      suggesting an association between PI3K/Akt signaling and Ca2+ influx. In
      conclusion, the results of the present study suggest that propofol treatment
      attenuates mast cell degranulation via inhibiting the miR-221/PI3K/Akt/Ca2+
      pathway. These results indicate that propofol may have a potential therapeutic
      effect as a treatment for allergic diseases.

PMID- 30116393
TI  - 8p11 Myeloproliferative syndrome with t(8;22)(p11;q11): A case report.
AB  - The 8p11 myeloproliferative syndrome (EMS), a rare myeloproliferative disease,
      generally progresses rapidly and is characterized by chromosomal translocations
      of the fibroblast growth factor receptor 1 (FGFR1) gene. The FGFR1 gene is
      located at chromosome 8p11 and may fuse with distinct partner genes. The
      breakpoint cluster region gene located at chromosome 22 is one of these partner
      genes. The patients' clinical phenotype is primarily dependant on the partner
      gene that translocates with FGFR1. Of all the available examinations,
      determination of the chromosome karyotype is most essential for the diagnosis of
      EMS. In addition, regarding treatment, allogeneic hematopoietic stem cell
      transplantation is currently the optimal method. The present study presented a
      case of 8p11 myeloproliferative syndrome with t(8;22)(p11;q11). This represents a
      total of 8 and 11 chromosomal translocations, which form a BCR/FGFR1 fusion gene
      in the patient to produce the abnormal karyotype: 46,XY,t(8;22)(p11;q11). The
      difference between the current case and other EMS incidences is that the patient
      progressed slowly and the clinical manifestation was similar to chronic myeloid
      leukemia (CML).

PMID- 30116392
TI  - Preliminary investigation on the abnormal mechanism of CD4+FOXP3+CD25high
      regulatory T cells in pediatric B-cell acute lymphoblastic leukemia.
AB  - The current study aimed to investigate the changes and regulatory mechanism of
      cluster of differentiation (CD)4+CD25high forkhead box protein 3 (Foxp3+)
      regulatory T cells (Tregs) in childhood B-cell acute lymphocytic leukemia (B
      ALL). A total of 18 children with B-ALL and 15 age-matched healthy children were
      included. Reverse-transcription quantitative polymerase chain reaction was used
      to evaluate the mRNA levels of Foxp3, cytotoxic T-lymphocyte associated protein 4
      (CTLA4), glucocorticoid-induced tumor necrosis factor receptor (GITR), lymphocyte
      activation gene 3 (LAG3), interleukin (IL)-2 receptor (R)beta/gamma, IL
      6Ralpha/beta, mothers against decapentaplegic homolog (Smad)3/4 and runt-related
      transcription factor (RUNX)1/3 in CD4-positive cells. The concentration of
      cytokines in plasma were measured using a cytometric bead array. Additionally,
      the proportion of CD4+CD25highFoxp3+ Tregs and levels of associated proteins was
      analyzed using flow cytometry. The results demonstrated that the proportion of
      CD4+CD25highFoxp3+ and expression of Foxp3 in children with B-ALL was
      significantly higher compared with healthy controls (P<0.05) and that
      transcription levels of CTLA4, GITR and LAG3 were also significantly elevated
      (P<0.05). Compared with healthy controls, the expression of IL-2Ralpha/beta and
      its downstream molecule phosphorylated signal transducer and activator of
      transcription 5 (pSTAT5) in CD4-positive cells significantly increased (P<0.05);
      however, no significant difference of IL-2Rgamma levels was identified between
      the two groups. Correlation analysis demonstrated a significant positive
      correlation between the expression of phosphorylated (p) signal transducer and
      activator of transcription factor (STAT)5 and CD4+CD25highFoxp3+ Tregs in
      children with B-ALL (r=0.17; P<0.05). The plasma concentration of TGF-beta, the
      expression of its receptor TGF-betaRI/II and downstream molecules Smad3/4 were
      significantly upregulated in children with B-ALL (P<0.05), whereas the expression
      of RUNX1/3 was lower compared with healthy controls (P<0.05). Furthermore, the
      expression of Smad3 and RUNX1 was positively correlated with CD4+CD25highFoxp3+
      Tregs in children with B-ALL (r=0.87 and 0.60, respectively; P<0.05).
      Additionally, the expression of pSTAT3 in CD4-positive cells decreased
      significantly in pediatric patients with B-ALL when compared with healthy
      controls; however, plasma concentrations of IL-6 was significantly higher
      (P<0.05). Furthermore, a negative correlation was identified between pSTAT3 and
      CD4+CD25highFoxp3+ Tregs in pediatric patients with B-ALL (r=-0.39; P<0.05).
      However, no significant differences in IL-6Ralpha/beta expression were identified
      between the two groups. The results demonstrated that the excessive activation of
      IL-2/pSTAT5 and TGF-beta/Smad signaling, and insufficiency of pSTAT3 may be
      correlated with increased CD4+CD25highFoxp3+ Tregs in pediatric B-ALL.

PMID- 30116394
TI  - Effects of CoCl2-simulated hypoxia on the expression levels of matrix
      metalloproteinases in renal adenocarcinoma cells and renal tubular epithelial
      cells.
AB  - Renal cell carcinoma (RCC) and chronic kidney disease (CKD) are associated with
      hypoxia, but the effects of hypoxia on the process of angiogenesis in the two
      diseases are dramatically different. Some of matrix metalloproteinases (MMPs),
      such as MMP2 and MMP9, may have a role because they represent the most prominent
      family of proteinases associated with angiogenesis. In the present study, the
      differential response of human renal cell cancer cells (786-0), human renal
      tubular epithelial cells (HK-2) and human microvascular endothelial cells (HMEC
      1) to hypoxia with regards to the expression of MMP2, MMP9, MMP14, TIMP2, RECK
      was investigated. Cobalt chloride (CoCl2) treatment was used to simulate the
      hypoxia environment in RCC and CKD. The expression levels of HIF-1alpha, RECK,
      MMP2, MMP9, MMP14 and TIMP2 in HK2, 786-0 and HMEC-1 cells were determined by
      western blot analysis after incubation with varying concentrations of CoCl2 for
      24 h. It was indicated that the effects of hypoxia on the endogenous expression
      of RECK and MMP2 differed depending on the considered cell type. Notably, the
      RECK expression was significantly decreased in 786-0 cells under hypoxia, whereas
      this expression was slightly increased in HK2 and HMEC-1 cells. Furthermore, the
      MMP2 expression was significantly increased in HMEC-1 cells under hypoxia,
      whereas the expression was slightly decreased in HK2 and 786-0 cells. These
      results demonstrate that 786-0, HK2 and HMEC-1 cells respond differently under
      hypoxic conditions. Furthermore, MMP2 and RECK may serve divergent roles in HK2
      and HMEC-1 cells under hypoxic conditions.

PMID- 30116395
TI  - Concordance of 24-h intraocular pressure curve in patients with untreated
      unilateral primary open-angle glaucoma.
AB  - The present study aimed to assess the concordance of 24-h intraocular pressure
      (IOP) curves between glaucomatous and contralateral eyes for patients with
      untreated unilateral primary open-angle glaucoma (POAG). A total of 32 patients
      with unilateral POAG and 32 age-matched normal subjects were enrolled. The IOP
      measurements were performed every 2 h over a 24-h period. The concordance of the
      24-h IOP curves was assessed via the correlation coefficient (r), intraclass
      correlation coefficient (ICC) and repeated-measures analysis of variance (ANOVA).
      No significant difference was identified between all IOPs, as well as the mean,
      peak and trough IOP or IOP fluctuations of the paired eyes in the two groups. The
      strength of association of all IOPs was moderate in the glaucoma group (r, 0.752
      0.867) and the normal controls (r, 0.625-0.873). IOP readings at each time-point
      indicated a high agreement in the glaucoma group (ICC, 0.857-0.929) and the
      normal controls (ICC, 0.768-0.932). Repeated-measures ANOVA indicated that the 24
      h IOP curves of the paired eyes had parallel profiles in the two study groups
      (P=0.837 and P=0.897, respectively). The glaucoma patients had significantly
      higher proportions of all IOPs displaying absolute differences of >=2 and >=3
      mmHg (46.09 vs. 35.68%, P<0.001; 29.69 vs. 12.50%, P<0.001, respectively). In
      conclusion, the 24-h IOP curves of the paired eyes had parallel profiles in
      unilateral glaucoma patients and normal subjects. However, unilateral glaucoma
      patients had a significantly larger proportion of IOP differences of >=2 and >=3
      mmHg.

PMID- 30116396
TI  - Nobiletin protects PC12 cells from ERS-induced apoptosis in OGD/R injury via
      activation of the PI3K/AKT pathway.
AB  - Nobiletin (NOB) possesses multiple pharmacological effects, but its anti
      apoptotic property has acquired a great deal of attention. Endoplasmic reticulum
      (ER) stress (ERS)-induced apoptosis acts as the pivotal aetiology in neuronal
      oxygen-glucose deprivation and reoxygenation (OGD/R) injury. The aim of this
      study focused on whether NOB exerts neuro-protective effects on OGD/R injury by
      repressing ERS-induced apoptosis. The PC12 neuronal cell line was subjected to 4
      h OGD and 24 h reoxygenation following NOB treatment. A PI3K/AKT inhibitor
      (LY294002) was added during the mechanistic experiments. Cell viability, lactate
      dehydrogenase (LDH) release and apoptosis were determined. Western blotting was
      used to measure protein expression levels. The results showed that OGD/R caused
      neuronal damageas exhibited by the increase in LDH release and the reduction of
      cellular viability. Moreover, ERS-induced apoptosis was markedly stimulated by
      OGD/R in PC12 cells, as evidenced by the elevation in the apoptotic rate and
      protein levels of C/EBP homologous protein/glucose-regulated protein-78. However,
      NOB administration significantly reversed neuronal damage and the ERS-induced
      apoptosis in response to OGD/R injury. Mechanistic detections showed that the
      neuron-favorable and ERS-repressing contributions of NOB were, in part, a result
      of the activation of the PI3K/AKT pathway, which was validated by a specific
      PI3K/AKT inhibitor (LY294002). Therefore, NOB protects PC12 cells from ERS
      induced apoptosis in OGD/R injury mainly through enhancement of the PI3K/AKT
      pathway, which may provide a novel therapeutic avenue for the prevention of
      cerebral ischemia/reperfusion injury.

PMID- 30116397
TI  - Insulin-like growth factor 1/insulin-like growth factor 1 receptor signaling
      protects against cell apoptosis through the PI3K/AKT pathway in glioblastoma
      cells.
AB  - Glioblastoma multiforme (GBM) is a malignant tumor caused by complex pathological
      mechanisms, and is characterized by a high rate of cancer-related mortality and
      poor patient prognosis. Overgrowth of cancer cells, which results from the
      inhibition of cell apoptosis and/or the promotion of cell proliferation, leads to
      the progression of GBM. Therefore, studies into the regulatory mechanisms of
      cancer cell growth in GBM are required to identify potential therapeutic targets
      and improve treatment for GBM. In the present study, the role of insulin-like
      growth factor 1 (IGF1)/IGF1 receptor (IGF1R) signaling in the survival of GBM
      cells was evaluated. It was observed that IGF1 significantly inhibited the
      intrinsic and extrinsic pathways of apoptosis (P<0.05), and overexpression of
      IGF1R significantly promoted the survival of GBM cells (P<0.05). Moreover, both
      exogenous IGF1 and overexpression of IGF1R promoted the phosphorylation of
      protein kinase B (AKT), and inhibition of the phosphoinositide 3-kinase
      (PI3K)/AKT pathway significantly attenuated the inhibitory effects of IGF1/IGF1R
      on GBM apoptosis (P<0.05). Collectively, these findings indicate that IGF1/IGF1R
      promotes the survival of GBM cells through activation of the PI3K/AKT pathway.
      Therefore, inhibition of IGF1/IGF1R may be a viable therapeutic strategy to
      suppress the progression of GBM.

PMID- 30116399
TI  - Adjuvant rhubarb alleviates organs dysfunction and inhibits inflammation in heat
      stroke.
AB  - The aim of the present study was to investigate the effects of adjuvant rhubarb
      on the recovery of patients with heat stroke. A total of 85 patients with heat
      stroke were randomly assigned to two treatment groups: One group receiving
      conventional treatment for heat stroke (conventional group) and one group
      receiving rhubarb supplement in addition to conventional treatment (rhubarb
      group). Liver and kidney function parameters, Acute Physiology and Chronic Health
      Evaluation (APACHE) II scores, plasma interleukin-6 (IL-6), procalcitonin (PCT),
      C-reactive protein (CRP) levels and venous white blood cell count (WBC) were
      analyzed. The length of stay in the intensive care units (ICUs) and hospital were
      recorded. Kaplan-Meier curves were drawn to determine the 30-day survival of the
      patients. The results indicated that rhubarb supplementation significantly
      reduced the WBC, as well as CRP, PCT and IL-6 levels at treatment days 3-5.
      Furthermore, rhubarb intake was observed to limit heat stroke-induced damage to
      liver and kidney function by decreasing the abnormally high levels of plasma
      aspartate aminotransferase, alanine aminotransferase and creatinine. Finally,
      patients in the rhubarb group had shorter ICU and hospital stays as well as a
      lower APACHE II score than those in the conventional group. However, no
      significant difference in the 30-day mortality rate was observed between the two
      groups. In conclusion, rhubarb intake provided a significant benefit for patients
      with heat stroke by inhibiting systemic inflammation and mitigating liver and
      kidney injury.

PMID- 30116398
TI  - Peripheral blood mitochondrial DNA copy number as a novel potential biomarker for
      diabetic nephropathy in type 2 diabetes patients.
AB  - The mitochondrial DNA copy number (mtDNA-CN) is a surrogate measure of
      mitochondrial function and altered mtDNA-CN reflects the oxidant-induced cell
      damage. A previous study by our group demonstrated that a reduction in the renal
      mtDNA-CN is implicated in the pathogenesis of diabetic nephropathy (DN), a
      leading cause of end-stage renal disease in diabetic patients. In the present
      study, it was investigated whether the mtDNA-CN in the peripheral blood may be
      utilized as a biomarker for DN in type 2 diabetes (T2D) patients. The study
      included 50 non-diabetic and 100 diabetic subjects. The diabetic subjects were
      sub-divided based on their albumin-to-creatinine ratio (ACR) into T2D patients
      with normoalbuminuria (n=50), DN patients with microalbuminuria (n=29) and DN
      patients with macroalbuminuria (n=21). The mtDNA-CN was measured in the
      peripheral blood by real-time polymerase chain reaction analysis. Patients with
      DN had a lower mtDNA-CN than patients with T2D and healthy controls (P<0.05). A
      sub-group analysis with stratification by the ACR indicated that a decreased
      mtDNA-CN was associated with the severity and the presence of DN, as it was lower
      in DN patients with macroalbuminuria than in DN patients with microalbuminuria
      and T2D patients with normoalbuminuria (P<0.01). The area under the receiver
      operating characteristic curve (AUC) for mtDNA-CN was 0.916 (sensitivity, 86% and
      specificity, 74%) and 0.961 (sensitivity, 96% and specificity, 88%) for
      differentiating DN patients from T2D patients without DN and from healthy
      controls, respectively. Furthermore, the AUC of mtDNA-CN for differentiating DN
      patients with microalbuminuria from those with macroalbuminuria was 0.895
      (sensitivity, 83% and specificity, 85%). Multivariate analysis revealed that the
      mtDNA-CN was significantly associated with the occurrence and progression of DN,
      even after adjustment for age, mean blood pressure, glycated haemoglobin A1c and
      total cholesterol (P<0.05). In patients with DN, a decreased mtDNA-CN was
      negatively correlated with albuminuria and conventional risk factors for DN, and
      was positively correlated with the estimated glomerular filtration rate. The
      present results therefore suggest the utilization of circulating mtDNA-CN as a
      novel biomarker for the early diagnosis of DN and indicate the significance of
      decreased mtDNA-CN as another independent risk factor for DN.

PMID- 30116400
TI  - Paeoniflorin inhibits IL-1beta-induced MMP secretion via the NF-kappaB pathway in
      chondrocytes.
AB  - Paeoniflorin serves important cellular roles, exerting anti-cancer, anti
      inflammatory and anti-pulmonary fibrosis effects and possesses immune-modulatory
      properties. However, the exact role of paeoniflorin in the pathogenesis of
      osteoarthritis (OA) remains unclear. The aim of the present study was to
      investigate the effects of paeoniflorin on articular surfaces in vitro. Rat
      chondrocytes were cultured in vitro and an MTT assay was performed to assess
      chondrocyte survival. Following treatment with interleukin (IL)-1beta and
      paeoniflorin, the production of matrix metalloproteinases (MMPs) and tissue
      inhibitor of metalloproteinases-1 (TIMP-1) was examined using reverse
      transcription-quantitative polymerase chain reaction and western blotting. The
      interleukin (IL)-1beta-induced nuclear factor (NF)-kappaB pathway activation was
      also investigated. The results demonstrated that paeoniflorin was able to
      downregulate the expression of MMP and increase the expression of TIMP-1ntmRNA
      and protein in IL-1beta-induced rat chondrocytes. Furthermore, treating
      chondrocytes with paeoniflorin blocked the activation of NF-kappaB. These results
      suggest that paeoniflorin may serve am anti-catabolic role in the progression of
      OA and may be an effective preventative treatment for OA.

PMID- 30116401
TI  - Regulation of transforming growth factor beta-mediated epithelial-mesenchymal
      transition of lens epithelial cells by c-Src kinase under high glucose
      conditions.
AB  - Recent studies have reported that high glucose (HG) conditions may contribute to
      the acceleration of renal cell apoptosis and renal fibrosis by inducing
      epithelial-mesenchymal transition (EMT) of tubular epithelial cells, in which c
      Src kinase and transforming growth factor (TGF)-beta are key modulators. In the
      present study, the roles of c-Src kinase and TGF-beta in EMT of lens epithelial
      cells (LECs) under HG conditions were investigated. Results indicated human lens
      epithelial B3 (HLE-B3) cells under HG conditions exhibited significantly
      increased protein expression levels of phosphorylated c-Src (p-Src418) (P<0.05)
      and secreted a significantly increased amount of TGF-beta compared with HLE-B3
      cells under normal glucose conditions (P<0.05). Notably the c-Src inhibitor PP1
      and the activin receptor-like kinase 5 (ALK5) inhibitor SB431542 suppressed EMT
      of HLE-B3 cells. Results indicated that PP1 significantly inhibited the
      activities of c-Src and ALK5 and the secretion of TGF-beta, whereas SB431542 only
      significantly downregulated the protein expression levels and secretion of TGF
      beta (P<0.05). Following c-Src knockdown, the protein expression levels of p
      Src418, ALK5 and TGF-beta were significantly decreased, the secretion of TGF-beta
      was significantly suppressed (both P<0.05) and EMT was decreased in HLE-B3 cells.
      These results suggest that c-Src and TGF-beta may promote EMT of LECs under HG
      conditions, with c-Src as the upstream regulatory molecule. Thus, the signal axis
      of c-Src/TGF-beta in EMT of LECs may be a potential novel therapeutic target for
      the prevention of diabetic subcapsular cataract.

PMID- 30116402
TI  - Anti-inflammatory action of ambuic acid, a natural product isolated from the
      solid culture of Pestalotiopsis neglecta, through blocking ERK/JNK mitogen
      activated protein kinase signaling pathway.
AB  - Ambuic acid is an organic acid isolated from the solid culture of Pestalotiopsis
      neglecta, which is an endophytic fungus that widely exists in many species of
      plants. Ambuic acid has been reported to exert antimicrobial activity against
      Gram-positive bacterium. The aim of the present study was to investigate the
      inhibitory effect of ambuic acid on lipopolysaccharide (LPS)-induced inflammation
      in RAW264.7 macrophages. The results demonstrated that ambuic acid significantly
      suppressed the overproduction of nitric oxide (NO) and prostaglandin E2 (PGE2) in
      a dose-dependent manner. Furthermore, ambuic acid also inhibited the release of
      the proinflammatory cytokine interleukin-6 (IL-6) however, no inhibition of the
      release of tumor necrosis factor-alpha (TNF-alpha) was observed. Further
      investigations indicated that ambuic acid downregulated the LPS-induced high
      expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins,
      as well as inhibited the enzymatic activity of iNOS and COX-2. In addition,
      ambuic acid suppressed the phosphorylation of extracellular signal-regulated
      kinase 1/2 (ERK 1/2) and c-Jun N-terminal kinase (JNK) induced by LPS. However,
      ambuic acid did not inhibit the phosphorylation of p38 mitogen-activated protein
      kinase (MAPK), the degradation of IkappaB-alpha protein or the nuclear
      translocation of nuclear transcription factor-kappaB (NF-kappaB) p65 subunit.
      These results suggested that ambuic acid may exert anti-inflammatory action by
      blocking the activation of the ERK/JNK MAPK signaling pathway, without the
      involvement of the p38 MAPK or NF-kappaB signaling pathways.

PMID- 30116403
TI  - Systemic Alterations of Wnt Inhibitors in Patients with Prostate Cancer and Bone
      Metastases.
AB  - Purpose: Dickkopf-1 (DKK-1) and sclerostin seem to inhibit osteoblast activity by
      blocking the Wnt pathway, which leads to progression of metastatic prostate
      cancer (PC). However, it is unknown whether serum levels of these proteins are
      altered in PC patients with or without metastasis. The aim of this study was to
      assess DKK-1 and sclerostin serum levels in PC patients, including patients with
      bone metastases. Methods: The study cohort (N = 143) consisted of 53 controls
      with benign prostatic hyperplasia (BPH), 43 with localized PC (PC cM0), and 47
      had PC with metastasis (PC cM1). Serum levels of DKK-1 and sclerostin were
      measured by enzyme-linked immunosorbent assay. Results were compared using the
      Kruskal-Wallis tests; post hoc analysis was performed using the Tukey-Kramer
      test. Results: Mean DKK-1 levels in patients with BPH (2809.4 pg/ml) (p < 0.001)
      as well as PC cM1 (2575.5 pg/ml) (p = 0.001) were significantly higher than in
      patients with PC cN0 cM0 (1551.8 pg/ml). Among PC cM1 patients, median DKK-1
      levels were significantly lower in patients with castration-resistant disease
      compared to those with hormone-sensitive PC (p = 0.02); in contrast, sclerostin
      concentrations were elevated (p = 0.04). DKK-1 correlated with PSA in the cM1
      group (p = 0.03) and sclerostin correlated with PSA in the PC group (0.01).
      Conclusions: DKK-1 is involved in the progression of PC. DKK-1-mediated
      inhibition of osteoblasts, which contributes to tumor progression and osteolytic
      metastases, may also play a role in the development of metastases with
      osteoblastic features. The use of DKK-1 antibodies should be considered for
      studies including metastatic PC patients.

PMID- 30116404
TI  - Corrigendum to "Tyrosine Kinase Receptor Landscape in Lung Cancer: Therapeutical
      Implications".
AB  - [This corrects the article DOI: 10.1155/2016/9214056.].

PMID- 30116405
TI  - Serum Level of D-Lactate in Patients with Cystic Fibrosis: Preliminary Data.
AB  - D-Lactate is produced by the intestinal biota and later absorbed into
      circulation. Some patients with cystic fibrosis (CF) develop exocrine pancreatic
      insufficiency that may disturb the gut microbiome and enhance the production of D
      lactate. However, this concept has not been studied yet. The aim of the study was
      to assess D-lactate concentration in relation to the occurrence of clinical
      features, activity of CF, and diet composition in paediatric patients. Patients
      and Method. Serum concentrations of D-lactate were measured in 38 CF patients (19
      girls and 19 boys) from 6 months to 18 years of age. The analysis included age,
      sex, clinical symptoms, diet (the variety and calorie needs), the laboratory
      tests for pancreatic efficiency (serum levels of albumin and glucose, faecal
      elastase activity, and faecal fat index) and faecal calprotectin (the marker of
      intestinal inflammation), and parameters of liver damage and of cholestasis (the
      activity of aminotransferases, gamma-glutamyltransferase, level of bilirubin, and
      international normalized ratio). Results. The median level of D-lactate was 0.86
      MUg/ml (1Q-3Q: 0.48-2.03) and correlated with the CF severity in the Schwachman
      Kulczycki score, parameters of pancreatic insufficiency, and the presence of
      intestinal inflammation. An increased level of D-lactate was observed in the
      subgroup with pancreas insufficiency (1.05 versus 0.73; p < 0.05), parallel with
      an elevated level of calprotectin (0.948 versus 0.755; p = 0.08). There was no
      relationship between energy consumption and diet composition and serum D
      lactates. Conclusion. Serum D-lactate concentration in CF patients is a promising
      new marker of exocrine pancreatic insufficiency probably related to intestinal
      flora dysbiosis/overgrowth.

PMID- 30116406
TI  - MicroRNAs as Urinary Biomarker for Oncocytoma.
AB  - The identification of benign renal oncocytoma, its differentiation from malignant
      renal tumors, and their eosinophilic variants are a continuous challenge,
      influencing preoperative planning and being an unnecessary stress factor for
      patients. Regressive changes enhance the diagnostic dilemma, making evaluations
      by frozen sections or by immunohistology (on biopsies) unreliable. MicroRNAs
      (miRs) have been proposed as novel biomarkers to differentiate renal tumor
      subtypes. However, their value as a diagnostic biomarker of oncocytoma in urines
      based on mechanisms known in oncocytomas has not been exploited. We used urines
      from patients with renal tumors (oncocytoma, renal cell carcinoma: clear cell,
      papillary, chromophobe) and with other urogenital lesions. miRs were extracted
      and detected via qRT-PCR, the respective tumors analyzed by immunohistology. We
      found isocitrate dehydrogenase 2 upregulated in oncocytoma and oncocytic
      chromophobe carcinoma, indicating an increased Krebs cycle metabolism. Since we
      had shown that all renal tumors are stimulated by endothelin-1, we analyzed miRs
      preidentified by microarray after endothelin-1 stimulation of renal epithelial
      cells. Four miRs are proposed as presurgical urinary biomarkers due to their
      known regulatory mechanism in oncocytoma: miR-498 (formation of the oncocytoma
      specific slice-form of vimentin, Vim3), miR-183 (associated with increased CO2
      levels), miR-205, and miR-31 (signaling through downregulation of PKC epsilon,
      shown previously).

PMID- 30116407
TI  - Pathological Implication of Adipocytes in AAA Development and the Rupture.
AB  - Abdominal aortic aneurysm (AAA) is a vascular disease that involves the gradual
      dilation of the abdominal aorta followed by its rupture. AAA is closely
      associated with weakening of the vascular wall due to oxidative stress, chronic
      inflammation, and degradation of the extracellular matrix. No effective drug
      therapy is currently available for preventing aneurysm progression or rupture.
      Adipocytes in the vascular wall are reportedly closely associated with AAA
      development and rupture. Fiber degradation in the aneurysm wall is enhanced by
      increased numbers of adipocytes, and rupture risk may increase as well. Recent
      studies suggested that appropriate control of adipocytes in the vascular wall may
      be an important strategy to prevent AAA rupture, and further studies may aid in
      the establishment of a method for preventing AAA rupture by therapeutic drugs or
      functional foods. In this review, we summarize adipocyte function and the
      correlation between AAA and adipocytes.

PMID- 30116410
TI  - Efficacy of Preoperative Antibiotic Therapy for the Treatment of Vascular Graft
      Infection.
AB  - Objective: We aimed to assess the efficacy of preoperative antibiotic therapy for
      the treatment of prosthetic graft infection. Materials and Methods: We
      retrospectively analyzed the treatment strategies used for managing patients with
      prosthetic vascular graft infections between 2000 and 2016. The patients were
      divided into two groups: early antibiotic (EA) group, those who were administered
      with antibiotics >=2 weeks preoperatively and late antibiotic (LA) group, those
      who were administered with antibiotics <2 weeks preoperatively. We evaluated the
      outcomes including surgical procedures, length of hospital stay, and surgical
      revision. Results: All the surgical procedures performed in the EA group were
      elective surgeries. Three of the 11 surgeries performed in the LA group were
      emergency surgeries (P=0.16). No significant differences were observed in the
      operative procedure (P=0.64), operation time (P=0.37), and blood loss (P=0.63) of
      the two groups. Although the length of postoperative hospital stay did not
      significantly differ (P=0.61), the total length of hospital stay was longer in
      the EA group (P=0.02). Surgical revisions were performed for five patients in the
      LA group and for none in the EA group (P=0.04). Conclusion: Preoperative
      antibiotic therapy provided excellent outcomes in terms of avoiding surgical
      revisions in the treatment of vascular graft infection.

PMID- 30116409
TI  - Transposed Brachial-Basilic Arteriovenous Fistula for Vascular Access in Japan.
AB  - As more than 320,000 patients are currently receiving hemodialysis treatment in
      Japan, the creation and maintenance of hemodialysis access is a major concern.
      The national guidelines recommend autogenous arteriovenous hemodialysis, and the
      brachial-basilic arteriovenous fistula has been the focus of attention, because
      the need for secondary, tertiary, or even more vascular access is growing.
      Although favorable results have been reported in terms of patency and access
      related complication, this fistula involves various unsolved or controversial
      issues, with limitations including complex procedures, which might contribute to
      the lower prevalence at this point in Japan. This review addresses those issues
      and discusses the role of fistula in Japan.

PMID- 30116408
TI  - Multiple Roles of Tenascins in Homeostasis and Pathophysiology of Aorta.
AB  - Tenascins are a family of large extracellular matrix (ECM) glycoproteins. Four
      family members (tenascin-C, -R, -X, and -W) have been identified to date. Each
      member consists of the same types of structural domains and exhibits time- and
      tissue-specific expression patterns, suggesting their specific roles in embryonic
      development and tissue remodeling. Among them, the significant involvement of
      tenascin-C (TNC) and tenascin-X (TNX) in the progression of vascular diseases has
      been examined in detail. TNC is strongly up-regulated under pathological
      conditions, induced by a number of inflammatory mediators and mechanical stress.
      TNC has diverse functions, particularly in the regulation of inflammatory
      responses. Recent studies suggest that TNC is involved in the pathophysiology of
      aneurysmal and dissecting lesions, in part by protecting the vascular wall from
      destructive mechanical stress. TNX is strongly expressed in vascular walls, and
      its distribution is often reciprocal to that of TNC. TNX is involved in the
      stability and maintenance of the collagen network and elastin fibers. A
      deficiency in TNX results in a form of Ehlers-Danlos syndrome (EDS). Although
      their exact roles in vascular diseases have not yet been elucidated, TNC and TNX
      are now being recognized as promising biomarkers for diagnosis and risk
      stratification of vascular diseases.

PMID- 30116411
TI  - Open Surgical Decompression Is Useful for the Prevention and Treatment of
      Abdominal Compartment Syndrome after the Repair of Ruptured Abdominal Aortic and
      Iliac Artery Aneurysm.
AB  - Objective: This study was performed to determine whether open surgical
      decompression (OSD) decreased the mortality associated with abdominal compartment
      syndrome (ACS) following open repair (OR) of ruptured abdominal aortic aneurysm
      and iliac aneurysm (rAAA), and to investigate the risk factors associated with
      OSD. Material and Methods: Total 113 consecutive patients with rAAA underwent OR
      in our institution. Ninety patients underwent primary abdominal closure; however,
      three of them developed ACS and required OSD. Prophylactic OSD was performed at
      the initial OR in 23 patients. Results: The in-hospital mortality rate was higher
      in those who underwent OSD than in those who did not undergo OSD [27.0% (7/26)
      vs. 6.9% (6/87), respectively; p=0.01]. However, no ACS-related death occurred in
      the OSD group. Multivariate analyses revealed that a preoperative/intraoperative
      base excess (BE)<-11 [p=0.045; odds ratio (OR), 3.33; 95% confidence interval
      (CI), 1.021-10.850], performance of left thoracotomy (p=0.038; OR, 5.17; 95%CI,
      1.098-24.357), and intraoperative blood transfusion >1,800 mL (p=0.012; OR, 4.30;
      95%CI, 1.386-13.322) were associated with OSD. Conclusion: The prevalence and
      mortality rates of ACS were low at our institution. OSD is considered to be
      useful for the prevention and treatment of ACS after repair of rAAA. OSD should
      be considered in patients with the above-mentioned factors.

PMID- 30116412
TI  - Graft Inclusion Technique: A New Flow Reduction Procedure for High Flow
      Arteriovenous Fistulae.
AB  - Objective: Flow reduction is required to preserve vascular access in cases with
      high flow access (HFA). We report a new flow reduction procedure, the graft
      inclusion technique (GIT). Methods: The GIT procedure developed by us involves
      the intraluminal placement and suturing of a 4-mm polytetrafluoroethylene graft
      to the anastomosis and outflow tract to plicate the enlarged anastomosis and
      maintain lower flow volumes. Flow reduction for HFA was retrospectively assessed
      in a series of 25 patients (age 65+/-12 years; 17 males and 8 females) to
      evaluate flow volume and patency rate, wherein 10 patients underwent conventional
      methods of flow reduction and 15 underwent GIT. Results: Compared with
      preprocedure values, mean flow volume (MFV) was significantly lower after the
      procedure with both the conventional methods (1,817 vs. 586 ml/min; P<0.05) and
      the GIT (2,262 vs. 890 ml/min; P<0.05). An increase in MFV occurred during follow
      up after conventional flow reduction (586 vs. 1,036 ml/min), while GIT could
      maintain lower MFV (890 vs. 791 ml/min), suggesting that GIT can significantly
      lower MFV levels (2,262 vs. 791 ml/min; P<0.05) and maintain these lower MFV
      levels during follow-up. Secondary patency rate for the GIT was 100% at 1 year
      and 83% at 3 years. Conclusion: The GIT may be used as an access-preserving,
      reliable, long-term, and stable flow-reducing procedure that does not require
      flow adjustment during surgery.

PMID- 30116413
TI  - Review of Transmetatarsal Amputations in the Management of Peripheral Arterial
      Disease in an Asian Population.
AB  - Objective: To evaluate outcomes after transmetatarsal amputation (TMA) in
      peripheral arterial disease (PAD) limb salvage in an Asian population and
      identify risk factors associated with TMA failure. Methodology: A retrospective
      review of 147 patients with PAD, who had undergone TMA between 2008 and 2014, was
      carried out. Univariate and multivariate analysis were used to identify
      predictors of TMA failure. Kaplan-Meier survival analysis was used to calculate
      major amputation and all-cause mortality rates. Results: The mean age was 66
      years. 92% were diabetic patients and 78% had preceded angioplasty. 56% of TMAs
      were healed via secondary intention, 8% required subsequent split-thickness skin
      graft closure, 24% required further debridement while 37% had wounds, which
      failed to heal and required below-knee amputations (BKA). Multivariate analysis
      showed that diabetes is the only independent predictor of TMA failure (odds ratio
      (OR) 7.11, p=0.064). Patients with TMA failure were at increased risk of
      developing nosocomial infections (p=0.025) and faced a higher risk of 30-day re
      admission rate (p=0.002). Conclusion: The success rate for PAD limb salvage TMA
      was 63% and diabetes was an independent predictor of TMA failure. Patients with
      TMA failure were at increased risks of nosocomial infections, and 30-day re
      admissions; hence the risks and benefits of TMA for diabetic foot limb salvage
      must be individualized for each patient.

PMID- 30116415
TI  - Transposed Basilic Vein Fistula: A Credible Option.
AB  - Objective: Native fistula creation for hemodialysis in patients who have
      exhausted all their superficial veins presents a challenge to vascular practice.
      We review our experience in transposed basilic vein fistula (BVT) creation and
      its usage for hemodialysis. Materials and Methods: We analyzed the hospital
      operative registry from January 2009 till June 2012 to identify the total number
      of BVT created in our center. Medical records of all patients were traced, and
      patients were interviewed using a standard proforma. In our center, BVT is
      performed as a two-stage procedure. All patients were routinely assessed with
      duplex scan preoperatively and postoperatively. Results: Two hundred thirty-nine
      patients were recruited in the study. Of these patients, 50.6% were male and
      49.4% were female. Mean age was 53.4 years. Of these patients, 81.2% had history
      of other previous fistula creation. Risk factors profile includes diabetes
      mellitus in 59.8%, hypertension in 86.2%, and smoking in 13.0%. Of these
      patients, 84.5% had no operative complication. Commonest complication was wound
      infection, 6.3%, followed by hemorrhage or hemotoma required surgical
      intervention, 5.9%, and pseudoaneurysm, 1.3%. Primary and secondary patencies
      were at 84.2% and 86.1% at 1 year and 67.7% and 70.5% at 3 years, respectively.
      Conclusion: BVT is a credible option for challenging patients with absence of
      superficial veins for native fistula creation with good patency and low operative
      complication rate. Preoperative ultrasound assessment improves patient selection
      and outcome of BVT.

PMID- 30116414
TI  - Long-Term Results of Crossover Bypass for Iliac Atherosclerotic Lesions in the
      Era of Endovascular Treatment: The Re-ACTION Study (Retrospective Assessment of
      Crossover Bypass as a Treatment for Iliac LesiONs).
AB  - Objective: The aim of this study was to elucidate the long-term results of
      crossover bypass (CB) for iliac atherosclerotic lesions in the era of
      endovascular treatment (EVT). Methods: A retrospective multicenter cohort study
      was performed. CB was performed in 242 patients between 2003 and 2014 by vascular
      surgeons at multiple medical centers in Japan. Results: Perioperative mortality
      was 1.7%. Primary patency rates were 86% at 5 years and 82% at 8 years.
      Univariate analysis showed that critical limb ischemia (Rutherford class 4-6),
      vein graft, and superficial femoral artery occlusion were significantly
      associated with low primary patency. In multivariate analysis, only critical limb
      ischemia influenced primary patency. The secondary patency rate was 87% at both 5
      and 8 years. The limb salvage rate was 98% at both 5 and 8 years. The overall
      survival rates were 71% at 5 years and 49% at 8 years. Conclusion: The long-term
      results of CB were good in our study, compared with previous reports. Our results
      suggest that CB remains an option for the arterial reconstruction in unilateral
      iliac occlusive disease after EVT failed.

PMID- 30116418
TI  - Hybrid Repair for Ruptured Thoracic Aortic Aneurysm: Frozen Elephant Trunk
      Technique with Thoracic Endovascular Aortic Repair.
AB  - We present a case of ruptured thoracic aortic aneurysm (TAA) with type B aortic
      dissection in which hybrid repair, namely, the frozen elephant trunk (FET)
      technique with thoracic endovascular aortic repair (TEVAR), was performed. The
      TAA extended to the proximal descending aorta at the level of the pulmonary trunk
      bifurcation. We thus employed the FET technique to control the blood flow into
      the TAA. After performing the FET technique, intraoperative catheter aortography
      revealed slight type 1B endoleak. We therefore performed additional TEVAR to
      control the blood flow into the TAA. The patient's postoperative course was
      uneventful.

PMID- 30116416
TI  - Early and Mid-Term Outcomes after Vascular Reconstruction for Patients with Lower
      Extremity Soft-Tissue Malignant Tumors.
AB  - Objective: To evaluate limb-salvage surgery including vascular resection for
      lower-extremity soft-tissue sarcomas and carcinomas for adult patients. Materials
      and Methods: Eight consecutive patients (median age, 59 years) who underwent
      vascular replacement during surgery for malignant tumors in the lower limbs
      between November 2006 and March 2018 were evaluated. Patient data were
      retrospectively obtained in a computerized database. Arterial and venous
      reconstructions were performed for seven patients, with one additional patient
      receiving venous reconstruction only. Autologous-vein (n=6) and synthetic
      bypasses were used for arterial repairs, whereas only autologous veins were
      implanted for venous repairs. Results: Morbidity was 62.5%, and in-hospital
      mortality was 12.5%. At a median follow-up of 24 months, the primary patency
      rates of arterial and venous reconstructions were 85.7% and 62.5%, respectively.
      Limb salvage was achieved in all cases. Conclusion: Early and mid-term bypass
      patency rates, the high percentage of limb salvage, and the oncologic outcome
      underline the efficacy of en bloc resection of soft-tissue tumors involving major
      vessels of the lower limbs. The anticipated need for vascular resection and
      reconstruction should not be a contraindication to sarcoma and carcinoma
      resections. However, efforts to achieve better control over systemic spread are
      required for long-term survival.

PMID- 30116417
TI  - A Case of Anastomotic Stenosis of a Peripheral Arterial Bypass Graft Undetected
      in Indocyanine Green Angiography.
AB  - We report the case of a 75-year-old man who underwent right femoral-popliteal
      bypass surgery. Anastomotic stenosis was overlooked in indocyanine green (ICG)
      angiography due to opacification on the bypass graft. X-ray angiography revealed
      slit-shaped stenosis in the distal graft anastomosis that required revision.
      Although blood flow may be maintained despite of anastomotic stenosis, small
      decreases in blood flow cannot be detected in ICG angiography. We describe and
      discuss the pitfalls of qualitative graft assessment using ICG angiography, and
      compare ICG fluorescence luminance intensity between primary and revised grafts.

PMID- 30116419
TI  - Infected Abdominal Aortic Aneurysm Caused by Campylobacter Jejuni.
AB  - A 69-year-old man presented with abdominal pain. Enhanced computed tomography
      (ECT) showed abdominal aortic aneurysm (AAA) with vessel wall thickening. Follow
      up ECT on day 3 of admission showed expansion of the AAA. Endovascular abdominal
      aortic repair (EVAR) was urgently performed. Since preoperative blood cultures
      revealed Campylobacter jejuni infection, the antibiotics imipenem/cilastatin were
      administered for five weeks, followed orally by Clarithromycin. The patient was
      discharged on postoperative day 45. There was no recurrence of the aneurysm at 9
      months after EVAR. To the best of our knowledge, this is the first report of EVAR
      for infected AAA caused by Campylobacter jejuni.

PMID- 30116420
TI  - Surgical Experience of a Case of Primary Leiomyosarcoma of the Left Common Iliac
      Artery That Presented as Acute Heart Failure Involving an Arteriovenous Fistula.
AB  - Primary leiomyosarcoma of the left common iliac artery with development of an
      arteriovenous fistula is extremely rare. Here we report the case of a 78-year-old
      woman with primary vascular leiomyosarcoma that presented as acute heart failure
      involving an arteriovenous fistula. She underwent surgery; however, after the
      diagnosis of leiomyosarcoma, she did not seek active treatment. She died 8 months
      after the surgery. This case report supports the need to document and follow-up a
      primary leiomyosarcoma of the iliac artery, especially when a case includes the
      presentation of an arteriovenous fistula (AVF). Vascular leiomyosarcoma should be
      included in the differential diagnosis of an AVF.

PMID- 30116421
TI  - Efficacy of Two-Dimensional Perfusion Angiography for Evaluations after
      Infrapopliteal Bypass Surgery for Critical Limb Ischemia.
AB  - Two-dimensional perfusion angiography (2DPA) is utilized in hybrid operating
      rooms. 2DPA produces color map images and functional parameters to provide more
      robust visual and quantitative evaluations than conventional angiography. Its
      efficacy was suggested in five patients following bypass surgery; unexpected
      results were obtained in one patient, leading to a decision to perform surgical
      re-anastomosis. Furthermore, we found that the general anesthesia eliminates body
      movements that tend to disrupt 2DPA results. 2DPA was more useful during surgical
      revascularization than conventional angiography and provided more detailed
      information.

PMID- 30116422
TI  - Elucidating the Functional Relationship Between Speed of Information Processing
      and Speed-, Capacity-, and Memory-Related Aspects of Psychometric Intelligence.
AB  - Numerous studies reported a positive relationship between speed of information
      processing (SIP) and the g factor of intelligence. Only very few studies,
      however, examined SI P's relationship to speed-, capacity-, and memory-related
      aspects of psychometric intelligence. In order to further elucidate this
      relationship, a Hick reaction time task and the Berlin Intelligence Structure
      (BIS) test were administered to 240 participants. From the BIS test, indicators
      of BIS -Capacity, BIS -Speed, and BIS -Memory were determined. By means of fixed
      links modeling, we subdivided variance in reaction time from the Hick task into a
      component representing individual differences in speed directly related to the
      systematically increased number of possible responses and another component
      representing individual differences in speed associated with residual sources
      unrelated to the experimental variation of response alternatives. While the
      former speed component was primarily related to BIS -Capacity and, to a lesser
      extent, to BIS -Speed, the latter one was only weakly related to BIS -Speed but
      unrelated to BIS -Capacity. None of the two speed components from the Hick task
      showed an association with BIS -Memory. Our findings indicate that individual
      differences in SI P caused by experimentally increasing the number of possible
      responses were more strongly associated with capacity- than with speed-related
      aspects of psychometric intelligence. In addition, individual differences in SI P
      not associated with the experimental manipulation of response alternatives showed
      rather weak relationships to each of the three BIS operations and could be
      considered equally strong.

PMID- 30116423
TI  - Dear Readers, Authors, Reviewers and Editorial Board Members of Advances in
      Cognitive Psychology.
AB  - In this first newsletter of 2018, we wanted to inform you about the current
      status of the journal. As our co-editor in chief (RL ) recently moved from the
      University of Finance and Management (UFMFM) in Warsaw to the Adam Mickiewicz
      University (AMU) in Poznan, the ownership of the journal or the editorial board
      might possibly change in the near future. Currently, different options are
      explored, and we will keep you informed on future changes. These changes may also
      have an impact on article processing fees (see also below).

PMID- 30116424
TI  - The Role of the Gut Barrier Function in Health and Disease.

PMID- 30116426
TI  - Feasibility of Underwater Endoscopic Mucosal Resection for Colorectal Lesions: A
      Single Center Study in Japan.
AB  - Background: Underwater endoscopic mucosal resection (U-EMR) has emerged as an
      alternative technique for the resection of colorectal lesions. This study aimed
      to evaluate our initial experience using U-EMR. Methods: This is a single-center,
      retrospective case series study. We analyzed the clinical outcomes of consecutive
      patients who underwent U-EMR in our endoscopy center, from December 2015 to
      February 2017. Results: Our analysis included 64 lesions, contributed by 38
      patients, with a mean age of 68.6 years (range, 25 to 90 years). The study sample
      included 33 right-sided and 25 left-sided colon lesions, and seven rectal
      lesions, with an average size of 16.2 mm (6 - 40 mm). Of these, 46 lesions were
      polypoid and 18 ones non-polypoid. Histologically, 31 lesions were low-grade
      adenomas, eight ones were high-grade adenomas, 11 were mucosal cancers, four were
      submucosal cancers, and 10 were classified as "others". En bloc resection was
      achieved in 52 (81%) lesions, with an en bloc resection rate of 95% for lesions <
      20 mm and 55% for lesions >= 20 mm. Complete resection of neoplastic epithelial
      lesions, defined by a negative pathological margin, was achieved in 32 of 59
      neoplastic epithelial lesions (54%). We identified three cases (5%) of post
      procedural bleeding and one case of perforation (2%). Conclusions: U-EMR can be
      feasibly used for resection of colonic lesions, including lesions >= 20 mm,
      although the en bloc resection rate for these lesions was lower than for lesions
      < 20 mm.

PMID- 30116425
TI  - Difference Between Left-Sided and Right-Sided Colorectal Cancer: A Focused Review
      of Literature.
AB  - Colorectal cancer is the third most common cancer worldwide with a high mortality
      rate at the advanced stages. However, colorectal cancer is not a single type of
      tumor; its pathogenesis depends on the anatomical location of the tumor and
      differs between right side and left side of the colon. Tumors in the proximal
      colon (right side) and distal colon (left side) exhibit different molecular
      characteristics and histology. In the right-sided tumors, mutations in the DNA
      mismatch repair pathway are commonly observed; and these tumors generally have a
      flat histology. In the left-sided tumors, chromosomal instability pathway-related
      mutations, such as KRAS, APC, PIK3CA, p53 mutations are observed and these tumors
      demonstrate polypoid-like morphology. Therapy responses are totally different
      between these tumor entities. Left-sided colorectal cancer (LCRC) patients
      benefit more from adjuvant chemotherapies such as 5-fluorouracil (5-FU)-based
      regimes, and targeted therapies such as anti- epidermal growth factor receptor
      (EGFR) therapy, and have a better prognosis. Right-sided colorectal cancer (RCRC)
      patients do not respond well to conventional chemotherapies, but demonstrate more
      promising results with immunotherapies because these tumors have high antigenic
      load. For the development of effective therapy regimes and better treatment
      options, it is essential to evaluate right-sided and left-sided tumors as
      separate entities, and design the therapy regime considering the differences
      between these tumors.

PMID- 30116428
TI  - Should We Measure Adenoma Detection Rate for Gastroenterology Fellows in
      Training?
AB  - Background: Adenoma detection rate (ADR) is a proven quality metric for
      colonoscopy. The value of ADR for the evaluation of gastroenterology fellows is
      not well established. The aim of this study is to calculate and evaluate the
      utility of ADR as a measure of competency for gastroenterology fellows. Methods:
      Colonoscopies for the purposes of screening and surveillance, on which
      gastroenterology fellows participated at the Richard L. Roudebush VAMC (one of
      the primary training sites at Indiana University), during a 9-month period, were
      included. ADR, cecal intubation rate, and indirect withdrawal time were measured.
      These metrics were compared between the levels of training. Results: A total of
      591 screening and surveillance colonoscopies were performed by 14 fellows. This
      included six, four and four fellows, in the first, second and third year of
      clinical training, respectively. Fellows were on rotation at the VAMC for a mean
      of 1.9 months (range 1 to 3 months) during the study period. The average ADR was
      68.8% (95% CI 65.37 - 72.24). The average withdrawal time was 27.59 min (95% CI
      23.45 - 31.73). The average cecal intubation rate was 99% (95% CI 98-100%). There
      was no significant difference between ADRs, cecal intubation rates, and
      withdrawal times at different levels of training; however, a trend toward swifter
      withdrawal times with advancing training was noted. Conclusions: ADR appears not
      to be a useful measure of competency for gastroenterology fellows. Consideration
      should be given to alternative metrics that could avoid bias and confounders.

PMID- 30116429
TI  - Impact of Hyoscine Bromide Use on Polyp Detection Rate During Colonoscopy: A
      Systematic Review and Meta-Analysis.
AB  - Background: Colorectal cancer (CRC) is a leading cause of death worldwide. Polyp
      detection rate (PDR) and adenoma detection rate (ADR) are key focus in endoscopic
      research for CRC screening and prevention. Use of anti-spasmodic agents during
      colonoscopy to help identify adenomas and polyps has remained a controversial
      topic. Hyoscine butyl bromide (HBB) is the most commonly used anti-spasmodic
      agent in patients undergoing colonoscopy. Some randomized controlled trials
      (RCTs) have questioned the clinical efficacy and safety of routine use of HBB for
      polyp and adenoma detection rates. Methods: We conducted a systematic search in
      PubMed and MEDLINE from inception until February 10, 2018, for studies which
      compared HBB with placebo. We used RevMan version 5.3 for analysis. Procedural
      end-points were polyps, adenomas, and advanced adenoma detection rates, mean
      number of polyps detected and cecal intubation time. Results: We included seven
      RCTs with 2,588 patients in our analysis. A total of 1,301 patients were
      randomized to HBB arm and 1,287 to the placebo arm. There was no significant
      difference in the primary outcome of polyp detection rate, 654 in HBB group vs.
      616 in the placebo group, (odds ratio (OR) = 1.11, confidence interval (CI) =
      0.93 - 1.34, P = 0.25). There was no difference in secondary outcomes of adenoma
      detection rate, 430 in HBB group vs. 396 in the placebo group, (OR = 1.06, CI =
      0.89 - 1.26, P = 0.51), advanced adenoma detection rate, 92 in HBB vs. 95 in
      placebo group (OR = 0.95, CI = 0.70 - 1.30, P = 0.76), mean number of polyps
      detected (point estimate = 0.12, CI = 0.00 - 0.23, P = 0.05), adenomatous polyps
      (OR = 0.84, CI = 0.39 - 1.81, P = 0.65) and cecal intubation time (point estimate
      = 0.73, CI = -1.98 - 0.52, P = 0.25) between the two groups. Conclusions: The use
      of HBB in patients undergoing colonoscopy does not appear to improve polyp or
      adenoma detection rates. It showed a non-significant trend of increased mean
      number of polyps detected with HBB.

PMID- 30116430
TI  - Relationship Between the Intraperitoneal Stent Length in Endoscopic Ultrasound
      Guided Hepaticogastrostomy and Surgically Altered Upper Gastrointestinal Anatomy
      in Patients With Malignant Biliary Obstruction.
AB  - Background: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is
      associated with a relatively high proportion of adverse events, and this is
      attributable to the lack of standardized protocols and specialized equipment.
      Although the outcomes of EUS-HGS may differ between patients with and those
      without surgically altered upper gastrointestinal anatomy, there have been no
      reports on this topic. The present study aimed to evaluate the efficacy and
      safety of EUS-HGS using our standardized method and to compare the outcomes
      between patients with and those without surgically altered upper gastrointestinal
      anatomy. Methods: In EUS-HGS, we used a long partially covered metal stent, and
      we kept the gastric wall pressed with the scope tip until the stent was deployed
      more than 1 cm inside the working channel of the scope to minimize free space
      between the liver and gastric wall (the intraperitoneal stent length). A total of
      12 patients who underwent EUS-HGS using our method were retrospectively studied.
      Procedural success and adverse events were evaluated, and the outcomes of EUS-HGS
      were compared between six patients with and six without surgically altered upper
      gastrointestinal anatomy. Results: The procedural success rate was 100%.
      Additionally, stent migration or dislocation was not noted in any of the
      patients. The intraperitoneal stent length was significantly greater in patients
      without surgically altered upper gastrointestinal anatomy than in those with
      surgically altered upper gastrointestinal anatomy (19.8 mm vs. 11.6 mm; 95%
      confidence interval, 2.185 - 14.147; P = 0.012). Conclusions: EUS-HGS using our
      method was safe. Our findings suggested that special attention should be paid to
      stent migration or dislocation in patients without surgically altered upper
      gastrointestinal anatomy.

PMID- 30116427
TI  - Profile of Gut Hormones, Pancreatic Hormones and Pro-inflammatory Cytokines in
      New Zealand Maori.
AB  - Background: Maori, indigenous people of New Zealand, have at least two times
      higher prevalence of obesity and diabetes in comparison with the general
      population in the country. Gut and pancreatic hormone profile differences as well
      as pro-inflammatory milieu may contribute to this disparity. The aim was to
      investigate the differences in gut hormones, pancreatic hormones and pro
      inflammatory cytokines between Maori and non-Maori individuals. Methods: This was
      a cross-sectional study. Fasting blood samples were collected to measure
      cholecystokinin, ghrelin, gastric inhibitory peptide, glicentin, glucagon-like
      peptide-1 and -2, oxyntomodulin, secretin, amylin, C-peptide, glucagon, insulin,
      pancreatic polypeptide, somatostatin, interleukin-6, monocyte chemoattractant
      protein-1 and tumour necrosis factor-alpha. Binary logistic regression analysis
      was conducted in one unadjusted and four adjusted statistical models adjusting
      for patient-, metabolic- and pancreatitis-related factors. Results: A total of 8
      Maori and 85 non-Maori individuals were included. Circulating levels of ghrelin,
      pancreatic polypeptide and interleukin-6 levels were significantly higher in
      Maori (P = 0.005, P = 0.003 and P = 0.011, respectively) in both unadjusted and
      all the four adjusted analyses. Other signaling molecules did not show
      consistently significant associations with ethnicity. Conclusion: Profile of gut
      hormones, pancreatic hormones and pro-inflammatory cytokines appears to differ
      between Maori and non-Maori individuals, independent of obesity, diabetes and
      other covariates. This may go some way to explain the increased propensity to
      obesity and diabetes in the Maori population.

PMID- 30116432
TI  - Metachronous Granular Cell Tumor of the Descending Colon.
AB  - Granular cell tumors (GCTs) are uncommon tumors. They are believed to be neuronal
      in origin and are usually found in the head and/or neck area of the body. They
      have also been reported in various locations of the gastrointestinal (GI) system,
      usually discovered during routine screening colonoscopy. We report a case of GCT
      in a 58-year-old asymptomatic African American female as a metachronous tumor of
      a well-differentiated adenocarcinoma of the sigmoid colon, which was an
      incidental finding in screening colonoscopy. To our knowledge, this is the first
      case with GCT identified as a metachronous tumor following an adenocarcinoma of
      the colon.

PMID- 30116431
TI  - Association Between Vitamin D Levels and Treatment Response to Direct-Acting
      Antivirals in Chronic Hepatitis C: A Real-World Study.
AB  - Background: Low serum vitamin D levels in chronic hepatitis C (CHC) is associated
      with advanced liver fibrosis; and there remains an imprecise relationship with
      the treatment response based on the vitamin D levels. Previous studies have shown
      conflicting results on the vitamin D levels, and association with treatment
      response in CHC treated with interferon-based regimens. Methods: Patients with
      CHC treated with direct-acting antivirals (DAAs) between January 2016 and
      December 2017 in the community clinic setting were retrospectively analyzed.
      Pretreatment baseline patient characteristics, treatment efficacy with the
      sustained virologic response at 12 weeks post-treatment (SVR 12) were assessed in
      CHC patients with deficient, insufficient, and normal levels of vitamin D
      measured before the initiation of DAA therapy. Results: Two hundred and ninety
      one patients were included in the study. Direct-acting antivirals included in the
      study were ledipasvir/sofosbuvir +/- ribavirin, ombitasvir + paritaprevir +
      ritonavir + dasabuvir +/- ribavirin, and sofosbuvir/velpatasvir. An overall
      sustained virologic response was achieved in 95% (n = 276) of patients. SVR 12
      rates among patients with vitamin D deficiency, vitamin D insufficiency and
      normal vitamin D levels were 92%, 96.2%, and 97.2% respectively and was not
      statically significant (P = 0.214). A total of 71 patients were cirrhotic. The
      prevalence of vitamin D insufficiency (20 - 29.9 ng/mL) and deficiency (< 20
      ng/mL) was significantly higher in cirrhotic patients (P = 0.01). Despite this,
      pretreatment vitamin D levels did not show any impact on the virologic response.
      The most common adverse effect observed was fatigue. None of the patients had to
      discontinue the treatment due to adverse events. Conclusions: DAAs are safe and
      effective with a high overall SVR 12 in CHC and treatment response does not
      depend on the pretreatment vitamin D levels. The prevalence of both vitamin D
      insufficiency and deficiency was observed to be higher in cirrhotic cohorts
      compared to non-cirrhotic counterparts.

PMID- 30116433
TI  - A Rare Case of Systemic Lupus Erythematosus with Gastric Ulcer and Acute
      Pancreatitis: A Case Report and Literature Review.
AB  - Systemic lupus erythematosus (SLE) is a chronic inflammatory disease which can
      manifest in many different organ systems. Gastrointestinal (GI) involvement is
      common in SLE, but the symptoms are usually mild. More severe GI complications
      including acute pancreatitis and peptic ulcer bleeding are rare but represent a
      significant risk of morbidity and mortality. We present a case of a 25-year-old
      Hispanic female with a severe SLE flare. The initial presentation included
      symptoms of hematemesis and epigastric abdominal pain secondary to both gastric
      ulceration and acute pancreatitis, an atypical presentation of an SLE flare. The
      non-specific symptom of abdominal pain makes both acute pancreatitis and gastric
      ulcer disease a clinical challenge; however, clinicians need to have a high
      suspicion for these conditions co-existing at the same time due to higher
      mortality rates.

PMID- 30116434
TI  - Endoscopic Appearance and Management of Recto-Sigmoid Endometriosis: Case Report.
AB  - Endometriosis is the presence of endometrial glands outside the uterine cavity.
      Endometriosis can involve any part of the bowel but most commonly affects the
      recto-sigmoid part of the bowel. This case shows the endoscopic views of bowel
      endometriosis and also elaborates on how to approach and manage similar cases of
      bowel endometriosis. Patients with bowel endometriosis are better managed and
      treated with a multidisciplinary team including gastroenterologist, gynecologist
      and colorectal surgeon.

PMID- 30116435
TI  - Spontaneous Expulsion per Rectum of a Colorectal Polyp: A Rare and Unusual Case.
AB  - Colorectal polyps are growths that form on the epithelium of the colon and
      rectum. While their prevalence varies considerably from region to region, they
      are common in adults. In fact, among asymptomatic, average-risk individuals at 50
      years of age, the prevalence of colorectal polyps averages roughly 10% in
      sigmoidoscopy studies and more than 25% in colonoscopy studies. Approximately two
      thirds of all colorectal polyps are adenomatous precancerous lesions that have
      the potential to become malignant. Usually, they are discovered and resected
      during colonoscopy. The spontaneous expulsion per rectum of a colorectal polyp is
      exceedingly rare. Here, we report a rare and unusual case that we believe is the
      first of spontaneous expulsion of an adenomatous polyp during defecation. These
      patients should undergo colonoscopy to search for additional polyps as well as
      other gastrointestinal pathology.

PMID- 30116436
TI  - The Clinical Use of Stem Cell Research in Chronic Obstructive Pulmonary Disease:
      A Critical Analysis of Current Policies.
AB  - Chronic obstructive pulmonary disease (COPD) is a disorder affecting more than
      200 million people around the world, resulting in three million deaths per year.
      COPD is characterized by the loss of lung tissue and airway remodelling, with
      chronic inflammation of the airways and progressive destruction of lung
      parenchyma. The use of stem cells may lead to regenerative processes that address
      biological damage. However, this approach raises ethical issues that need to be
      considered in clinical trials using stem cell therapy, such as informed consent,
      patient recruitment and harm minimization, as well as the inherent uncertainty of
      these medical procedures on human beings. Indeed, up to now, these experiments
      have been performed in preclinical studies using animal models, with few studies
      involving humans. Additional efforts should be made to assess this promising
      procedure.

PMID- 30116437
TI  - Long-Term Effects of Ipragliflozin on Diabetic Nephropathy and Blood Pressure in
      Patients With Type 2 Diabetes: 104-Week Follow-up of an Open-Label Study.
AB  - Background: In our previous study, we investigated the efficacy of ipragliflozin,
      a sodium-glucose cotransporter (SGLT) 2 inhibitor on diabetic nephropathy in
      patients with type 2 diabetes and demonstrated that ipragliflozin significantly
      improved diabetic nephropathy in addition to reducing HbA1c and body weight.
      Herein, we conducted post-trial monitoring to determine whether these lowering
      effects on blood glucose and body weight or the beneficial effects on diabetic
      nephropathy were maintained long-term (104 weeks) after starting ipragliflozin
      treatment. Methods: Initially, during a 24-week interventional trial period, a 50
      mg dose of ipragliflozin was administered to 50 patients with type 2 diabetes
      without changing other treatments. During the post-trial monitoring period, these
      patients returned to hospital-based diabetes care according to their clinical
      needs. We continued monitoring their clinical data for 104 weeks in each hospital
      and analyzed the results on an intention-to-treat basis. Results: The
      improvements in glycemic control and body weight reduction provided by 24-week
      ipragliflozin administration were maintained for 104 weeks. Despite a transient
      decrease during the intervention period, the estimated glomerular filtration rate
      (eGFR) was restored to near the baseline level at 104 weeks. Notably, in patients
      with diabetic nephropathy, the median urinary albumin-to-creatinine ratio (UACR)
      was significantly decreased from 119.2 (98.9 - 201.8) at baseline to 36.9 (19.7 -
      204.7) mg/gCr at 104 weeks. In addition, eGFR was stable for 104 weeks, showing
      no decrease. In contrast, a significant positive correlation between UACR and
      blood pressure observed at 24 weeks disappeared after discontinuation of the
      intervention therapy. Conclusions: The well-controlled HbA1c and body weight
      reductions were maintained for 104 weeks of post-trial follow-up. Moreover,
      ipragliflozin significantly reduced urinary albumin excretion in patients with
      diabetic nephropathy without decreasing eGFR.

PMID- 30116439
TI  - Suicidal Ideation and Suicide Attempts in Middle-Aged Women Attending a Primary
      Care Center: A Cross-Sectional Study in Mexico.
AB  - Background: Very little is known about suicide attempts in middle-aged women in
      Mexico. The aims of this study were to determine: 1) the prevalence of suicidal
      ideation and suicide attempts in middle-aged women in Durango City, Mexico; and
      2) the suicide attempt prevalence association with the sociodemographic,
      clinical, and behavioral characteristics of the women studied. Methods: Through a
      cross-sectional study, 395 middle-aged women were surveyed. Suicidal ideation,
      suicide attempt data, and the characteristics of the women were obtained with the
      aid of a questionnaire. Bivariate and multivariate analyses were used to
      determine the association between suicide attempts and the characteristics of
      women. Results: Of the 395 women (mean age: 46.97 +/- 5.34 years) studied, 50
      (12.7%) had suicide ideation, and 20 (5.1%) had suicide attempts. The number of
      suicide attempts among these 20 women varied from 1 to 10 times. The most
      frequent method used for suicide attempt was intake of medicaments (in 11 women).
      None of the sociodemographic characteristics was associated with suicide
      attempts. Women with suicide ideation, abdominal pain frequently, and reflexes
      impairment had a significantly higher frequency of suicide attempts than those
      without these characteristics. Logistic regression of behavioral variables showed
      that only the variable alcohol consumption was independently associated with
      suicide attempts (odds ratio = 2.82; 95% confidence interval: 1.01 - 7.84; P =
      0.04). Conclusions: Results suggest that suicidal ideation and suicide attempts
      are prevalent among women of middle-age attending a public primary care center in
      Durango City. This is the first report of an association between suicide attempts
      and reflexes impairment. Factors associated with suicide attempts found in this
      study may help in the design of preventive measures against suicide.

PMID- 30116438
TI  - Vulvovestibular Syndrome and Vaginal Microbiome: A Simple Evaluation.
AB  - Background: The vulvovestibular syndrome (VVS) is a chronic, inflammatory,
      multifactorial, chronic inflammation of the female urogenital access. Methods:
      The aim of this anecdotal, observational, retrospective, case-control study was
      to comparatively evaluate the most common bacterial strains (Lactobacillus spp.,
      Klebsiella spp., Gardnerella spp., and Streptococcus spp.) and fungi (Candida
      spp., Pennicillum spp., and Aspergillus spp.) in vulvodinic women, and in women
      without gynecological symptoms (control group). Results: We found that vulvodinic
      patients had statistically lower Lactobacilli and higher total Fungi
      concentration. Conclusions: Our preliminary study is useful to further clarify
      the etiopathology of vulvodynia and suggest new therapeutic strategies for
      approaching the VVS.

PMID- 30116440
TI  - Soluble Fms-Like Tyrosine Kinase-1 Is A Marker of Endothelial Dysfunction During
      Sepsis.
AB  - Background: Sepsis is currently defined as a life-threatening organ dysfunction
      caused by a deregulated host response to infection. There is increasing evidence
      that the endothelium plays a crucial and pathogenic role in sepsis. Profound
      alterations of the endothelium associated with sepsis include increased
      leucocytes adhesions, shift to a procoagulant state, vasodilatation, altered
      barrier function with more permeable capillaries and tissue edema. The vascular
      endothelial growth factor (VEGF) pathway is involved in the control of
      microvascular permeability and has been involved in the pathogenesis of
      conditions associated with endothelial barrier disruption such as sepsis. sFlt-1
      is a soluble variant of the VEGF receptor (Fms-like tyrosine kinase-1, Flt-1 or
      VEGFR-1) able to down-regulate the effects of VEGF by decreasing its signaling.
      We investigated the possible involvement of sFlt-1 as biomarker of endothelial
      alteration during sepsis, organ dysfunction and death. Methods: Serum levels of s
      Flt1 were measured in 170 hospitalized patients (77 with sepsis, confirmed by
      positive blood culture), and in 18 healthy volunteers. The sequential organ
      failure assessment (SOFA) score was determined by using biochemical and clinical
      parameters. In a small number of patients (9 individuals), s-Flt1 concentration
      was evaluated after negativization of the blood culture. Results: Serum level of
      s-Flt1 was significantly higher in septic patients than blood culture-negative
      patients (277.7 +/- 52.7 and 133.4 +/- 12.4 pg/mL, respectively, P = 0.0088),
      both groups of patients had significantly higher concentration of sFlt-1 than
      healthy individuals (78.9 +/- 2.5 pg/mL). Among sepsis cases, 68% was caused by
      Gram-negative bacteria, 27% by Gram-positive bacteria and 8% by Candida species.
      Serum level of s-Flt1 showed a significant difference between Gram-negative
      (274.1 pg/mL) and Gram-positive (145.7 pg/mL) sepsis. SOFA score (evaluated in 20
      patients with sFlt-1 >190 pg/mL) showed a positive trend of correlation with the
      increasing sFlt-1 level. After blood culture negativization, serum level of sFlt
      1 decreased (37%). Conclusion: Our findings confirm, in a larger population of
      patients with sepsis, recent evidences that sFlt-1 levels are higher in patients
      with complicated-sepsis that evolve to septic shock and suggest that sFlt-1 could
      be a useful biomarker for sepsis severity. An anti-VEGF effect mediated by sFlt-1
      could be hypothesized as salvage compensatory mechanism activated in response to
      sepsis.

PMID- 30116441
TI  - Low Vitamin D Deficiency Associated With Thyroid Disease Among Type 2 Diabetic
      Mellitus Patients.
AB  - Background: The aim of this study was to investigate the relationship between
      vitamin D deficiency and thyroid diseases among type 2 diabetes mellitus (T2DM)
      patients. Methods: This was a cohort case and control study, 546 T2DM patients
      and 546 control study participants were enrolled, aged between 25 and 65 years.
      The subjects were also investigated for fasting blood glucose levels (FBG), post
      prandial glucose (PPG,) glycosylated hemoglobin (HbA1c), thyroid stimulating
      hormone (TSH), T3, T4, and presence of other comorbid conditions. Thyroid fine
      needle aspiration biopsy was suggested to patients whose thyroid nodules were
      greater than 1.00 cm. Results: There were significant differences between T2DM
      patients and control subjects regarding BMI (kg/m2), physical activity, cigarette
      smoking, sheesha smoking, family history of diabetes, hypertension and family
      history of thyroid nodules. The clinical biochemistry values among T2DM for
      vitamin D, calcium, magnesium, potassium, phosphorous, fasting blood glucose,
      cholesterol, HbA1c, HLDL, LDL, triglyceride, systolic blood pressure (SBP) and
      diastolic blood pressure (DBP) were lower than control subjects, but higher in
      creatinine, albumin, TSH, T3, and T4 which appeared statistically significant
      differences (P < 0.001). Also, the study revealed statistically significant
      differences between subjects vitamin D deficiency and with thyroid nodules for
      calcium, magnesium, phosphorous, HbA1c, high density lipoprotein (HDL), SBP and
      DBP, TSH, T3, and T4 among T2DM patients and control subjects (P < 0.001).
      Multivariable stepwise logistic regression analysis showed that TSH, HbA1c,
      vitamin D deficiency, SBP (mm Hg), BMI, family history of DM, serum calcium level
      and family history of thyroid were considered at higher risk as predictors of
      thyroid among T2DM patients. Conclusions: This study suggests that obesity,
      HbA1c, the environment, and genetic susceptibility among T2DM, may increase the
      risk of thyroid disease and cancer. Although evidence has shown that thyroid
      cancer incidence has been rising more rapidly over time than the occurrence of
      cancers of other sites, due to an increase of obesity, diabetes and lack of
      physical activity, this study lacks of direct evidence supporting this
      conclusion.

PMID- 30116442
TI  - Relationship Between Depression and Stress Coping Ability Among Residents in
      Japan: A Two-Year Longitudinal Study.
AB  - Background: Depression among medical residents is a critical issue. The early
      detection of depression and provision of appropriate care is necessary for
      fostering healthy conditions during clinical training. To investigate whether
      Sense of Coherence (SOC), an indicator of stress coping ability, could be a
      predictor of depression 2 years after the start of clinical training, we
      conducted a national longitudinal study. Methods: We distributed self
      administered questionnaires to residents in 251 postgraduate educational
      hospitals just before the start of their clinical training. The questionnaire
      contained the Center for Epidemiologic Studies Depression (CES-D) scale (a
      screening tool for depression), the SOC scale, and demographic factors. After 2
      years, we distributed questionnaires to residents who responded to the first
      survey. The second questionnaire contained the CES-D scale and questions about
      working conditions. We categorized respondents into three groups according to
      their SOC score and analyzed the relationship between SOC groups (low, middle,
      high) and depressive symptoms on the follow-up survey. Results: In total, 1,738
      of 2,935 residents (59.2%) responded to the first survey. Of these, 1,169
      residents (67.3%) also responded to the follow-up survey. A total of 169
      residents were excluded because they screened positive for depressive symptoms at
      the time of the first survey. On the follow-up survey, 187 residents (19.5%) had
      new-onset depressive symptoms: 33.3% in the low SOC group, 18.2% in the middle
      SOC group, and 11.4% in the high SOC group (P < 0.01). Compared with the high SOC
      group, the odds ratio for new-onset depressive symptoms in the low SOC group was
      2.04 (95% confidence interval, 1.02 - 4.05) after adjusting for demographic
      factors, baseline CES-D score, and mean working time. Conclusions: SOC score is
      significantly associated with future depressive symptoms among residents after 2
      years. Residents in the low SOC group had a 2-fold higher risk of future
      depressive symptoms than those in the high SOC group. The SOC scale might be a
      useful predictor of future depression and allow for the provision of appropriate
      support to residents during clinical training.

PMID- 30116443
TI  - Acute Hepatic Failure and Epididymitis in a Hispanic Patient With Active Systemic
      Lupus Erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease known to affect a
      variety of organ systems. Patients with SLE are more prone to developing common
      infections that can mimic the complications of SLE. As such, it is essential to
      differentiate complications of SLE from infection to ensure appropriate
      management and to improve morbidity and mortality of this patient population.
      Here we present a 24-year-old, Hispanic male, with SLE complicated by dialysis
      dependent end-stage renal disease and dilated cardiomyopathy. The patient
      presented to the emergency room with nausea, vomiting, and abdominal pain and
      admitted to the medicine service. Initial evaluation showed hypoalbuminemia
      coupled with elevated transaminases, INR, and total bilirubin consistent with
      acute liver failure. Further evaluation was negative for viral, toxic, metabolic,
      or vascular causes of acute failure. The patient was diagnosed with lupus
      hepatitis and associated acute hepatic failure, and started on high dose
      prednisone (60 mg daily). Complete resolution of liver function and symptoms was
      observed within 1 week at follow-up. The patient was readmitted 2 weeks after
      discharge with left scrotal pain and swelling after abruptly decreasing the
      prescribed prednisone dose 3 days after discharge. Physical exam and scrotal
      ultrasound in the emergency department were consistent with epididymitis.
      Urinalysis, urine culture, and gonorrhea and chlamydia PCR were all negative.
      Without evidence of infection, and upon reconfirmation of low serum complement
      levels, the patient was diagnosed with lupus epididymitis and restarted on high
      dose prednisone. Complete resolution of symptoms was attained within 1 week at
      follow-up. This case emphasizes the importance of differentiating the clinical
      manifestations of SLE from infection and the complexity of disease presentation
      in Hispanic patients.

PMID- 30116445
TI  - Habit of Bathing or Showering Is Beneficially Associated With Body Weight and
      Abdominal Circumference in Patients With Type 2 Diabetes.

PMID- 30116444
TI  - Acute Delirium Associated With Levofloxacin.
AB  - Delirium is considered as the most common complication afflicting hospitalized
      elderly patients, accompanied by high morbidity and mortality rate; and despite
      its high prevalence, it often remains unrecognized. Drug-induced delirium is a
      well-known entity with sedatives, narcotics and anticholinergics most often
      implicated in its causation. Delirium attributed to antibiotics, mainly
      cephalosporins and macrolids, has been infrequently reported, and until yet only
      seven cases of levofloxacin-induced delirium have been described in the medical
      literature. We describe another case of delirium associated with levofloxacin in
      an elderly patient who was hospitalized in our medical ward for pneumonia. The
      present case and the other cases previously reported should raise the awareness
      of physicians to this serious, underestimated, and underdiagnosed adverse effect
      of a commonly used antibiotic, levofloxacin.

PMID- 30116446
TI  - Illustrating the Sense of a Network Meta-Analysis by Means of Dedicated Plots: A
      Way for Making It Conceptually Easier and More Immediately Understandable.

PMID- 30116447
TI  - Utilization of Echocardiogram, Carotid Ultrasound, and Cranial Imaging in the
      Inpatient Investigation of Syncope: Its Impact on the Diagnosis and the Patient's
      Length of Hospitalization.
AB  - Background: Although guidelines suggest that the best strategy for evaluating
      syncope is clinical history and physical examination, the inappropriate
      utilization of diagnostic imaging is common. Methods: A single center
      retrospective analysis conducted in adult patients admitted for evaluation and
      management of syncope for a period of 12 months. Charts were reviewed to abstract
      demographic data, admitting and discharge diagnosis, diagnostic investigatory
      tests including imaging modalities (echocardiogram, carotid ultrasound, and
      cranial computed tomography (CT)) ordered, subspecialty consultation requested,
      treatment rendered and hospital length of stay (LOS). Results: A total of 109
      patients were admitted for syncope, mean age was 68.74 +/- 21.04 years and 39.44%
      were men. Echocardiogram, carotid ultrasound, and cranial CT were ordered in
      69.72%, 33.02%, and 76.14% respectively. The mean hospital LOS was 2.6 days.
      Patients with no imaging test, one imaging test, two imaging tests, and three
      imaging tests ordered have an average hospital LOS of 2.22 days, 2.44 days, 2.58
      days, and 3.07 days respectively. The number of imaging test and its relation to
      the admitting (Chi-square (chi-sq) P = 0.4165, nominal logistic regression (LR) P
      = 0.939) and discharge (chi-sq P = 0.1507, nominal LR P = 0.782) diagnosis as
      well as the LOS in relation to the number of imaging test ordered (analysis of
      variance (ANOVA) P = 0.368, Kruskal Wallis (KW) P = 0.352) were not statistically
      significant although there was a trend of prolonged hospital LOS the more imaging
      diagnostic test had been ordered. Syncope was the admitting and discharge
      diagnosis in 89.9% and 91.74% respectively. Conclusions: Choosing the appropriate
      diagnostic tests as dictated by the patient's clinical manifestation and
      utilizing less expensive test would be appropriate and cost-effective approach in
      appraising patients with syncope.

PMID- 30116448
TI  - Appropriate and Inappropriate Implantable Cardioverter Defibrillators Therapies
      in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Patients.
AB  - Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is
      an inherited cardiomyopathy characterized histologically by the replacement of
      ventricular myocardium with fibrous and fatty tissue, and clinically by
      ventricular tachycardia arrhythmias primarily of right ventricular (RV) origin.
      Implantable cardioverter defibrillator (ICD) is the only proven therapy to reduce
      mortality in ARVC/D patients. However, it has the risk of inappropriate anti
      tachycardia pacing (ATP) or shocks. This study aimed to assess the occurrence of
      appropriate and inappropriate ICD therapies in ARVC/D patients who underwent ICD
      implantation in a single Cardiac Centre. Methods: Retrospective analysis of the
      data of patients with the diagnosis of ARVC/D based on the 2010 revised Task
      Force Criteria, who underwent ICD implantation in the Heart Centre, at King
      Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh between January
      1997 and May 2016. The clinical data and information about appropriate and
      inappropriate ICD therapies were obtained from medical records with the review of
      the available intra-cardiac electrograms (EGMs). Results: Twenty-two ARVC/D
      patients with ICD implantation (20 males (91%), mean age at ICD implantation: 32
      +/- 14 years). ICD was implanted for secondary prevention of sudden cardiac death
      (SCD) in 15 patients (68.2%), and for primary prevention in 7 patients (31.8%).
      At mean follow-up of 9.4 +/- 4.8 years, 11 patients (50%) had appropriate ICD
      therapies, and five patients (22.7%) had inappropriate ICD therapies. Out of 950
      ICD therapies, 865 (91%) were appropriate (586 episodes of VT/VF treated with ATP
      (61.3%), and 279 episodes treated with shocks (29.37%)) and 85 (9.4%) were
      inappropriate (45 episodes treated with ATP (4.73%), and 40 treated with shocks
      (4.21%)). Conclusion: ARVC/D patients are at risk of VT/VF arrhythmias. ICD
      therapy is the only proven life-saving therapy in those patients. Most of ICD
      therapies in our patient's population are appropriate, and ATP therapy is
      effective in terminating most of VT episodes. Although we do not have any patient
      with subcutaneous ICD, the high success rate of ATP suggests that transvenous ICD
      would be more appropriate in ARVC/D patients.

PMID- 30116449
TI  - Association of Tp-Te/QT Ratio With Ventricular Tachycardia in Patients With
      Idiopathic Outflow Tract Ventricular Premature Contraction.
AB  - Background: Idiopathic outflow tract ventricular premature contraction (VPC) can
      evolve into ventricular tachycardia (VT) via triggered activity mechanism.
      Transmural dispersion of repolarization (TDR) might play a role in idiopathic
      outflow tract VT by inducing phase 2 early afterdepolarization (EAD) and serve as
      the functional substrate for VT. Tp-Te/QT ratio as an arrhythmogenesis index has
      been reported to be associated with the incidence of ventricular arrhythmia. This
      study aims to investigate the association between Tp-Te/QT ratio with VT
      incidence in idiopathic outflow tract VPC. Methods: Observational research with
      cross sectional design was conducted. VT episodes were retrospectively tracked
      from electrocardiogram (ECG), treadmill test (TMT), Holter monitor and
      electrophysiology study data in Sardjito Hospital of patients with idiopathic
      outflow tract VPC during September to October 2017. Tp-Te/QT was defined as the
      time from the peak of T wave to the intersection between the tangent and
      isoeectric line, divided with QT interval. Tp-Te/QT ratio measurement was
      performed in leads V4, V5 and V6 by single observer. Tp-Te/QT ratio was
      categorized into increased (> 0.25) and normal (< 0.25). Chi-square and logistic
      regression test were performed. Results: Out of 46 patients, there were 28
      patients who had VT. Increased Tp-Te/QT ratio of lead V4 was found in 11
      patients, the increased ratios in leads V5 and V6 were found in 13 patients. The
      prevalence ratio (PR) of Tp-Te/QT ratio to VT incidence in lead V4 was 2.059 (95%
      CI: 1.464 - 2.895; P = 0.007), while in leads V5 and V6 was 2.200 (95% CI: 1.514 
      3.197; P = 0.002). Tp-Te/QT ratios in leads V4, V5 and V6 were not significantly
      different and equally strong in predicting VT events (P < 0.001; 95% CI).
      Adjustment of confounding factor hypertension with multivariate test gave
      insignificant results (PR: 1.290; 95% CI: 0.444 - 3.747). Conclusions: Increased
      Tp-Te/QT ratio in idiopathic outflow tract VPC patients was associated with
      higher prevalence ratio for VT, although this was affected by hypertension. Leads
      V4, V5 and V6 were equally strong in predicting VT events.

PMID- 30116450
TI  - Ivabradine Versus Beta-Blockers in Mitral Stenosis in Sinus Rhythm: An Updated
      Meta-Analysis of Randomized Controlled Trials.
AB  - Background: Symptoms of mitral stenosis (MS) are worsened during tachycardia and
      exercise. Beta-blockers are used in controlling heart rate (HR) in MS, resulting
      in symptom improvement, but coming with significant side effects. Ivabradine has
      a selective action on the sinus node devoid of the usual side effects of beta
      blockers. Small studies have recently investigated the role of ivabradine in MS
      in sinus rhythm. Our aim was to determine the efficacy of ivabradine, compared to
      beta-blockers, in terms of exercise duration, maximum HR achieved, resting HR,
      mean gradient, and working capacity among patients with MS in sinus rhythm.
      Methods: We conducted a systematic search of studies using MEDLINE, Google
      Scholar, ScienceDirect, Scopus, Clinical Key, Cochrane, and clinicaltrials.gov
      databases in all languages and examined reference lists of studies. We included
      studies if they are: 1) randomized controlled trials comparing ivabradine and
      beta-blockers; 2) of adults >= 19 years old with MS in sinus rhythm; and 3)
      reported data on exercise duration, maximum HR achieved, resting HR, mean
      gradient, and working capacity. Studies identified were assessed for risk of bias
      using the Cochrane Collaboration Tool for Assessing Risk of Bias. We used inverse
      variance analysis of fixed effects to compute for mean difference, carried out
      using Review Manager (RevMan) 5.3. Results: Pooled analysis from five identified
      trials showed that among patients with MS in sinus rhythm, ivabradine was better
      compared to beta-blockers in total exercise duration (mean difference: 32.73 s
      (95% CI: 12.19, 53.27; P = 0.002; I2 = 0%)), maximum HR achieved after exercise
      (mean difference: -3.87 beats per minute (95% CI: -5.88, -1.860; P = 0.0002; I2 =
      23%)), and work capacity (mean difference: 0.56 METS (95% CI: 0.33, 0.80; P <
      0.00001; I2 = 0%)); inferior to beta-blockers in resting HR achieved (mean
      difference: 1.83 s (95% CI: 0.39, 3.28; P = 0.01; I2 = 91%)); and comparable to
      beta-blockers in terms of mean gradient (mean difference: -0.52 mm Hg (95% CI: 
      1.20, 0.16; P = 0.13; I2 = 6%)). Conclusions: Ivabradine is better or comparable
      to beta-blockers in terms of the outcomes measured, and may be considered as an
      alternative for patients with MS in sinus rhythm who are intolerant to beta
      blockers.

PMID- 30116451
TI  - Usefulness of the Whole Blood Passage Time as a Predictor of Primary
      Cardiovascular Events in Patients With Traditional Cardiovascular Risk Factors.
AB  - Background: Recent clinical studies have reported that impaired hemorheology is a
      significant cardiovascular risk factor, but there has been no prospective study
      of its relationship with cardiovascular events. The aim of this prospective study
      was to assess the efficacy of whole blood passage time (WBPT), measured by a
      microchannel array flow analyzer (MC-FAN), as a predictor of primary
      cardiovascular events in patients with traditional cardiovascular risk factors.
      Methods: The study enrolled 1,134 outpatients with traditional cardiovascular
      risk factors but no history of cardiovascular events (438 men and 696 women; mean
      +/- standard deviation age, 67 +/- 11 years). Based on the value of WBPT, the
      patients were assigned to one of three groups: L (low, WBPT < 50 s; n = 499), M
      (medium, WBPT 50 - 70 s; n = 295), or H (high, WBPT > 70 s; n = 340). The utility
      of the WBPT as a predictor of primary cardiovascular events was evaluated.
      Results: During the follow-up period (median 81.9 months), major adverse
      cardiovascular events (MACE) occurred in 95 cases (L, 21 cases (4.2%); M, 24
      cases (8.1%); H, 50 cases (14.7%); P < 0.001, log-rank test). In multivariate Cox
      regression analyses, the risk for MACE was significantly higher in group H than
      in group L (hazard ratio, 2.32; 95% confidence interval, 1.31 - 3.20; P < 0.01).
      A WBPT cut-off of 72.4 s yielded the largest area under the curve of 0.705 (95%
      confidence interval: 0.678 - 0.732), with a sensitivity of 51.7% and specificity
      of 85.4% for discriminating between those who did and did not experience MACE
      during the follow-up period. Conclusion: This study showed that WBPT evaluated by
      a MC-FAN was a predictor of primary cardiovascular events in patients with
      traditional cardiovascular risk factors.

PMID- 30116452
TI  - A Community Level Sample Survey to Determine CurrentUnderstanding About Medical
      Recycling of Cardiovascular ImplantableElectronic Devices.
AB  - Background: Medical recycling and reutilization of cardiovascular
      implantableelectronic devices (CIEDs) have a significant impact not only in
      patientsof low-income countries but may also in certain patients in the
      UnitedStates who do not have sufficient medical insurance coverage. Themain
      determining factor for future utility and popularity of recycledmedical devices
      is thorough understanding about this topic amongstpublic and healthcare
      professional. To the best of our knowledge,there has been no study conducted so
      far at a community level to determinethe understanding in public and healthcare
      personnel about recyclingof medical devices including CIEDs. We sought to
      determine existingknowledge and attitude about recycling of CIEDs amongst
      representativesample population in a community. Methods: A questionnaire was sent
      for online completion to multiple peoplein the community, healthcare and funeral
      home in Lehigh Valley, Pennsylvania,USA. The questionnaire was designed in order
      to assess three maincategories; knowledge, attitude and practice. We called this
      a KAPstudy which is an acronym for knowledge, attitude and practice survey.
      Results: We got 117 responses to our questionnaire from community
      members(55.45%), 89 responses (42.18%) from the healthcare personnel andfive
      responses (2.37%) from funeral homes. About 30.77% communityparticipants had
      heard about medical devices recycling compared to57.30% participants from
      healthcare sector. A total of 88.64% of medicalprofessionals were aware that
      there are people in the world who diebecause they cannot afford CIEDs while
      73.50% of community participantswere also found to be aware of this fact. Higher
      percentages of healthcareprofessionals were found to be willing to personally
      consider a decisionabout medical device donation compared to community
      participants. Conclusions: CIED reutilization can improve quality of life among
      many patientswith low or medium socioeconomic status. People should be made
      moreaware about the benefits of CIED reutilization. Concerns about device
      relatedinfections, complications and law suits should be addressed to helpimprove
      their utility.

PMID- 30116453
TI  - Takotsubo Cardiomyopathy-Induced Cardiac Free Wall Rupture: A Case Report and
      Review of Literature.
AB  - Takotsubo cardiomyopathy (TCM) is an acquired form of cardiomyopathy that is
      commonly seen among post-menopausal women. It is characterized by left
      ventricular apical ballooning, electrocardiographic changes and mild elevation of
      cardiac enzymes in the absence of significant coronary artery stenosis. TCM
      usually has benign course. However, on rare instance, it can result in life
      threatening and fatal complications including acute cardiogenic shock,
      ventricular arrhythmias and ventricular wall rupture. We herein report a case of
      a 77-year-old female who developed TCM complicated with massive pericardial
      effusion and cardiac arrest. The patient died and autopsy revealed normal
      coronaries with a slit-like rupture on the antero-apical surface of the heart
      extending into the papillary muscle. The clinical course, labs and angiographic
      findings preceding the cardiac rupture will be outlined. A thorough literature
      review including review of 14 previously reported case reports of TCM complicated
      with cardiac rupture will be included.

PMID- 30116454
TI  - A Case of Pseudoinfarction Pattern in Diabetic Ketoacidosis: A Diagnostic and
      Therapeutic Dilemma.
AB  - Diabetic ketoacidosis (DKA) is regularly associated with hyperkalemia that
      results in well-described changes on the electrocardiogram (EKG). However, ST
      segment elevations on EKG mimicking acute myocardial infarction have rarely been
      described in the setting of DKA. Here we present a case of a 43-year-old male
      with DKA who had pseudoinfarction pattern of ST-segment elevation on EKG that
      resolved with treatment of DKA and discuss the diagnostic and therapeutic dilemma
      around the condition.

PMID- 30116455
TI  - "Superdominant" Left Anterior Descending Artery Continuing as Posterior
      Descending Artery: Extremely Rare Coronary Artery Anomaly.
AB  - The posterior descending artery (PDA) supplying the posterior one-third of the
      inter-ventricular septum usually arises from the right coronary artery (RCA) or
      the left circumflex artery (LCX). PDA arising from the left anterior descending
      artery (LAD) is an extremely rare anomaly. Here we report a rare type of left
      dominant circulation in which a large LAD is continuing as PDA after winding
      round the apex in the presence of a diminutive RCA. Such a large LAD continuing
      as PDA is referred as "hyperdominant" or "superdominant". A 32-year-old male
      chronic smoker presented with acute onset retrosternal pain of 4 h duration with
      profuse sweating in primary health center with electrocardiography (ECG) changes
      in inferior leads and was thrombolysed with intravenous streptokinase 15 lacs IU
      over one hour and was referred to our center for further management and coronary
      intervention. Coronary angiogram revealed PDA as a continuation of the LAD beyond
      the crux and a non-dominant right coronary as well as LCX. The LAD had plaque in
      mid-LAD course. Intravascular ultrasound study (IVUS) showed insignificant plaque
      in mid-LAD (30%). Hence, we decided to keep him on medical therapy only.

PMID- 30116456
TI  - Technical Considerations in Transradial Unprotected Left Main Stem Rotational
      Atherectomy-Assisted and IVUS-Guided Percutaneous Coronary Intervention Using the
      7.5F Eaucath Sheathless Guiding Catheter System.
AB  - Rotational atherectomy-assisted percutaneous coronary intervention (PCI) on
      unprotected left main stem (LMS) bifurcation lesions is technically challenging.
      Intravascular ultrasound (IVUS) has become a standard part of the PCI procedure
      for the treatment of LMS disease. There is limited experience in performing these
      cases via a transradial approach using a sheathless guiding catheter (SGC)
      system. We report a case of a symptomatic octogenarian patient with restrictive
      angina and significant LMS bifurcation disease, who was successfully treated
      transradially with the use of the 7.5F Eaucath SGC system and we describe the
      technical challenges encountered with this strategy.

PMID- 30116457
TI  - Congenital Absence of the Left Circumflex Artery With Super-Dominant Right
      Coronary Artery: Extremely Rare Coronary Anomaly.
AB  - Among the congenital anomalies of the coronary arteries, absent left circumflex
      artery (LCX) defect is extremely rare. Only a few cases have been reported in the
      literature. We report a case of a 48-year-old female who presented with a 4-month
      history of exertional chest pain with positive stress (treadmill) test.
      Conventional coronary angiogram showed a normal left anterior descending, absent
      LCX and a super-dominant right coronary artery (RCA) with prominent branches.
      Aortography also failed to show a separate ostium for the left circumflex artery.
      Multi-detector computed tomographic coronary angiography was performed to confirm
      the diagnosis of congenital absence of the LCX. It is a benign incidental
      finding, however some patients present with angina-like symptoms often resulting
      in detection of this rare anatomy on coronary angiography. Precise morphological
      and functional evaluation of the anomalous coronary artery is important for
      selecting the best treatment modality and better prognosis.

PMID- 30116458
TI  - Myocardial Stunning After Electrocution With Complete Reversibility Within 24
      Hours: Role of Repeat Transthoracic Echocardiograms in Potential Cardiac
      Transplant Donors.
AB  - Despite the development of ventricular assist devices, cardiac transplantation
      remains an important procedure for patients with advanced heart failure. The
      number of transplants done annually has remained stable because of lack of of
      donors. Left ventricular systolic dysfunction remains one of the most important
      reasons for seeking a donor heart. Myocardial stunning is an important cause of
      reversible systolic dysfunction. Electrical injury is a recognized cause of
      myocardial stunning with variable duration ranging from days to weeks. Repeating
      the transthoracic echocardiogram to look for reversibility of left ventricular
      dysfunction can be a cost-effective method to improve the selection of heart
      donors. This can significantly help to decrease critical organ shortage. We
      present a case of myocardial stunning after electrocution which was completely
      reversible within a few hours, thus meeting cardiac transplant donor criteria.

PMID- 30116459
TI  - Intrahepatic portal-venous shunts during PVE.
AB  - Portal venous embolization (PVE) is a well-validated technique to promote
      contralateral liver lobe hypertrophy prior to hepatic resection. We present a
      case of a patient with Type IV cholangiocarcinoma undergoing PVE prior to hepatic
      surgical resection. However, intrahepatic portal-venous shunts were incidentally
      found during the procedure and were subsequently embolized using embolic coils
      and N-butyl cyanoacrylate. While most patients with congenital portal-venous
      shunts remain asymptomatic, an unrecognized shunt during PVE could have resulted
      in a devastating complication secondary to nontarget embolization through the
      fistula. To our knowledge, this is the first reported case of a portal-venous
      shunt being discovered during a PVE.

PMID- 30116460
TI  - Bilateral sporadic carotid body tumors-A rare case report.
AB  - Carotid body tumor presents as palpable mass in anterolateral aspect of the neck.
      However, bilateral sporadic carotid body tumor is a rare anomaly, reported to
      occur in 5% of population. We are going to report the case of a 60-year-old
      patient who presented to our department with painless, palpable mass bilaterally
      in anterolateral aspects of the neck. He did not have any family history of neck
      masses. This paper summarizes the topic of carotid body tumor and discusses the
      radiological and clinical implications of this condition.

PMID- 30116461
TI  - Pelvic tuberculosis: a forgotten diagnosis - case report.
AB  - We present a case of a 14-year-old girl, Bacillus Calmette-Guerin (BCG)
      vaccinated, who presented with vague symptoms of abdominal pain, weight loss, and
      fatigue. Imaging studies revealed a pelvic mass, later found to be pelvic
      tuberculosis, a rare diagnosis to consider at this age. The diagnostic approach
      was difficult, since all investigations pointed strongly to a malignancy, from
      clinical, imaging (ultrasound and magnetic resonance), laboratory (elevated CA
      125), and even macroscopic findings at laparotomy. Histopathology was the first
      hint (noncaseous granulomata), but the ultimate documentation of Mycobacterium
      tuberculosis relied on a persistent clinical suspicion, despite contradicting
      results. Surgical approach could have been mutilating, with irreversible
      consequences, considering it was a girl with a long reproductive life ahead.
      Tuberculosis is still a great masquerade, especially the extrapulmonary forms,
      and although infrequently seen at this age, it should thus be considered in the
      differential diagnosis of complex pelvic masses in order to avoid surgical
      iatrogeny/morbidity.

PMID- 30116462
TI  - A rare case of co-existing adrenal and pelvic myelolipomas.
AB  - We are reporting a case of co-existing left sided pelvic and right sided adrenal
      myelolipomas in a 68-year-old male patient. Both lesions were incidentally
      discovered on CT whilst undergoing a staging scan for suspected urinary bladder
      cancer. The patient had a background of hypertension and type 2 diabetes.
      Contrast enhanced CT scan showed both lesions to be of mixed fat and soft tissue
      density. Given the size, location, and attenuation characteristics of the pelvic
      mass, retroperitoneal liposarcoma was thought to be a differential diagnosis,
      prompting the decision for an elective CT-guided biopsy. Both masses were
      targeted successfully using core biopsy needles. Subsequently, histopathology
      results for both the right adrenal and the left pelvic masses showed features
      compatible with myelolipomas. The right retroperitoneal mass was compatible with
      an adrenal myelolipoma and left pelvic mass was deemed as an extra-adrenal
      myelolipoma (EAML).

PMID- 30116463
TI  - Interstitial nephritis: Two pediatric cases with atypical radiological features.
AB  - Interstitial nephritis (IN) is a relatively rare entity in children and
      adolescents that can be caused by a range of disorders including infection,
      medications, inflammatory bowel disease, and sarcoid. There is no proven therapy
      for this condition. We present 2 cases of biopsy-proven interstitial nephritis,
      of which 1 case was with granulomatous features that presented with unusual
      sonographic findings of discrete mass lesions in the kidney parenchyma
      bilaterally. Although a precise cause could not be identified in either case, 1
      patient progressed to end-stage kidney disease (ESKD) and the other is in the
      early stages of treatment. We suggest that recognition of the atypical imaging
      features of interstitial nephritis may enable early recognition of this condition
      and avoid confusion with neoplastic or infectious processes.

PMID- 30116464
TI  - Stabilizing Lead-Free All-Inorganic Tin Halide Perovskites by Ion Exchange.
AB  - Because of its thermal stability, lead-free composition, and nearly ideal optical
      and electronic properties, the orthorhombic CsSnI3 perovskite is considered
      promising as a light absorber for lead-free all-inorganic perovskite solar cells.
      However, the susceptibility of this three-dimensional perovskite toward oxidation
      in air has limited the development of solar cells based on this material. Here,
      we report the findings of a computational study which identifies promising Rb y
      Cs1-y Sn(Br x I1-x )3 perovskites for solar cell applications, prepared by
      substituting cations (Rb for Cs) and anions (Br for I) in CsSnI3. We show the
      evolution of the material electronic structure as well as its thermal and
      structural stabilities upon gradual substitution. Importantly, we demonstrate how
      the unwanted yellow phase can be suppressed by substituting Br for I in CsSn(Br x
      I1-x )3 with x >= 1/3. We predict that substitution of Rb for Cs results in a
      highly homogeneous solid solution and therefore an improved film quality and
      applicability in solar cell devices.

PMID- 30116465
TI  - Probing Interactions between Electron Donors and the Support in MgCl2-Supported
      Ziegler-Natta Catalysts.
AB  - Olefin polymerization using Ziegler-Natta catalysts (ZNCs) is an important
      industrial process. Despite this, fundamental insight into the inner working
      mechanisms of these catalysts remains scarce. Here, we focus on the low-gamma
      nuclei 25Mg and 35Cl for an in-depth solid-state NMR and density functional
      theory (DFT) study of the catalyst's MgCl2 support in binary adducts prepared by
      ball-milling. Besides the bare MgCl2 support and a MgCl2-TiCl4 adduct, samples
      containing donors that are part of the families of 2,2-dialkyl-1,3
      dimethoxypropanes and phthalates used in fourth- and fifth-generation ZNCs are
      studied. DFT calculations indicate that the quadrupolar coupling parameters of
      the chlorines differ significantly between bulk and surface sites. As a result,
      the NMR visibility of the chlorine sites correlates with the particle size except
      for the adduct with 2,2-dimethyl-1,3-dimethoxypropane donor. The DFT calculations
      furthermore show that the surface sites are fairly insensitive to binding of
      different donor molecules, making it difficult to identify specific binding
      motives. The surface sites with large 35Cl NMR line widths can be observed using
      high radio frequency field strengths. For the 2,2-dimethyl-1,3-dimethoxypropane
      donor, we observe additional surface sites with intermediately high quadrupolar
      couplings, suggesting a different surface structure for this particular adduct
      compared to the other systems. For 25Mg, pronounced effects of donor binding on
      the quadrupole interaction parameters are observed, both computationally and
      experimentally. Again the adduct with the 2,2-dimethyl-1,3-dimethoxypropane donor
      shows a different behavior of the surface sites compared to the other adducts,
      which display more asymmetric coordinations of the surface Mg sites. Identifying
      specific binding motives by comparing 25Mg NMR results to DFT calculations also
      proves to be difficult, however. This is attributed to the existence of many
      defect structures caused by the ball-milling process. The existence of such
      defect structures both at the surface and in the interior of the MgCl2 particles
      is corroborated by NMR relaxation studies. Finally, we performed heteronuclear
      correlation experiments, which reveal interactions between the support and Mg-OH
      surface groups, but do not provide indications for donor-surface interactions.

PMID- 30116466
TI  - Quantifying High-Performance Material Microstructure Using Nanomechanical Tools
      with Visual and Frequency Analysis.
AB  - High-performance materials like ballistic fibers have remarkable mechanical
      properties owing to specific patterns of organization ranging from the molecular
      scale, to the micro scale and macro scale. Understanding these strategies for
      material organization is critical to improving the mechanical properties of these
      high-performance materials. In this work, atomic force microscopy (AFM) was used
      to detect changes in material composition at an extremely high resolution with
      transverse-stiffness scanning. New methods for direct quantification of material
      morphology were developed, and applied as an example to these AFM scans, although
      these methods can be applied to any spatially-resolved scans. These techniques
      were used to delineate between subtle morphological differences in commercial
      ultra-high-molecular-weight polyethylene (UHMWPE) fibers that have different
      processing conditions and mechanical properties as well as quantify morphology in
      commercial Kevlar(r), a high-performance material with an entirely different
      organization strategy. Both frequency analysis and visual processing methods were
      used to systematically quantify the microstructure of the fiber samples in this
      study. These techniques are the first step in establishing structure-property
      relationships that can be used to inform synthesis and processing techniques to
      achieve desired morphologies, and thus superior mechanical performance.

PMID- 30116467
TI  - Advanced SEM and TEM Techniques Applied in Mg-Based Hydrogen Storage Research.
AB  - Mg-based materials are regarded as one of the most promising candidates for
      hydrogen storage. In order to clarify the relationship between the structures and
      properties as well as to understand the reaction and formation mechanisms, it is
      beneficial to obtain useful information about the size, morphology, and
      microstructure of the studied materials. Herein, the use of scanning electron
      microscopy (SEM) and transmission electron microscopy (TEM) techniques for the
      representation of Mg-based hydrogen storage materials is described. The basic
      principles of SEM and TEM are presented and the characterizations of the size,
      morphology observation, phase and composition determination, and formation and
      reaction mechanisms clarification of Mg-based hydrogen storage materials are
      discussed. The applications of advanced SEM and TEM play significant roles in the
      research and development of the next-generation hydrogen storage materials.

PMID- 30116468
TI  - Three-Dimensional Atomic Force Microscopy for Sidewall Imaging Using Torsional
      Resonance Mode.
AB  - This article presents an atomic force microscopy (AFM) technique for true three
      dimensional (3D) characterization. The cantilever probe with flared tip was used
      in a home-made 3D-AFM system. The cantilever was driven by two shaking
      piezoceramics and oscillated around its vertical or torsional resonance
      frequency. The vertical resonance mode was used for upper surface imaging, and
      the torsional resonance mode was used for sidewall detecting. The 3D-AFM was
      applied to measure standard gratings with the height of 100 nm and 200 nm. The
      experiment results showed that the presented 3D-AFM technique was able to detect
      the small defect features on the steep sidewall and to reconstruct the 3D
      topography of the measured structure.

PMID- 30116469
TI  - Scanning Mortars to Understand the Past and Plan the Future for the Maintenance
      of Monuments.
AB  - The effect of microstructure on macroproperties of building materials was the
      initiation in order to use microscopic techniques for studying the materials'
      behavior. Primer role among the different techniques has the scanning electron
      microscope (SEM) as it provides much information in an easy and understandable
      way. SEM has been used in almost every study of the last decades, dealing with
      historic and repair materials to complete the analysis performed. In the case of
      historic mortars, it is a unique technique as it requires a small representative
      sample and without any intense treatment important information derived from an
      almost unknown sample including damage detection, phase identification, and
      microanalysis. It is usually a complementary method of analysis but a precious
      one as the gained results from the analysis of old mortars are used for designing
      compatible repair materials for restoration purposes. In the paper, the long-term
      use of SEM in studying both old authentic and innovative repair mortars is
      presented.

PMID- 30116470
TI  - Evaluation of Threshold Values for Root Canal Filling Voids in Micro-CT and Nano
      CT Images.
AB  - While several materials and techniques have been used to assess the quality of
      root canal fillings in micro-CT images, the lack of standardization in scanning
      protocols has produced conflicting results. Hence, the aim of this study was to
      determine a cutoff voxel size value for the assessment of root canal filling
      voids in micro-CT and nano-CT images. Twenty freshly extracted mandibular central
      incisors were used. Root canals were prepared with nickel titanium files to an
      ISO size 40/0.06 taper and then filled with a single cone (40/0.06 taper) and AH
      Plus sealer. The teeth were scanned with different voxel sizes with either micro
      CT (5.2, 8.1, 11.2, and 16.73 MUm) or nano-CT (1.5 and 5.0 MUm) equipment. Images
      were reconstructed and analyzed with the NRecon and CTAn software. Void
      proportion and void volume were calculated for each tooth in the apical, middle,
      and coronal thirds of the root canal. Kruskal-Wallis and post hoc Mann-Whitney U
      tests were performed with a significance level of 5%. In micro-CT images,
      significantly different results were detected among the tested voxel sizes for
      void proportion and void volume, whereas no such differences were found in nano
      CT images (p > 0.05). Micro-CT images showed higher void numbers over the entire
      root length, with statistically significant differences between the voxel size of
      16.73 MUm and the other sizes (p < 0.05). The values of the different nano-CT
      voxel sizes did not significantly differ from those of the micro-CT (5.2, 8.1,
      and 11.2 MUm), except for the voxel size of 16.73 MUm (p < 0.05). All tested
      voxel sizes enabled the detection of root canal filling voids except for the
      voxel size of 16.73 MUm. Bearing in mind the limitations of this study, it seems
      that a voxel size of 11.2 MUm can be used as a reliable cutoff value for the
      assessment of root canal filling voids in micro-CT imaging.

PMID- 30116471
TI  - Protective Effects of Fullerene C60 Nanoparticles and Virgin Olive Oil against
      Genotoxicity Induced by Cyclophosphamide in Rats.
AB  - The potential effects of the fullerene C60 nanoparticle (C60) as well as virgin
      olive oil (VOO) against the cyclophosphamide- (CP-) induced cytotoxic and
      mutagenic effects were evaluated by two main methods: molecular intersimple
      sequence repeat (ISSR) assay and cytogenetic biomarkers. Thirty adult male rats
      were divided to five groups (control, CP, C60, CP + C60, and CP + VOO). CP was
      i.p. injected with a single dose of 200 mg/kg; C60 and VOO were given orally (4
      mg/kg dissolved in VOO and 1 ml, resp.) in alternative days for 20 days. The ISSR
      analysis revealed an increased in the DNA fragmentation level for liver and heart
      tissues represented by 21.2% and 32.6%, respectively, in the CP group. The DNA
      polymorphism levels were modulated and improved in CP + C60 (8.9% and 12%) and CP
      + VOO (9.8% and 12.7%) for hepatic and cardiac tissues, respectively. The bone
      marrow cytogenetic analysis revealed that C60 and VOO had significantly decreased
      the frequency of CP-induced chromosomal aberrations (chromosomal ring, deletion,
      dicentric chromosome, fragmentation, and polyploidy). Fullerene C60 and VOO have
      ability to reduce DNA damage and decrease chromosomal aberrations. In conclusion,
      fullerene C60 and VOO have protective effects against the CP-induced mutagenicity
      and genotoxicity. Fullerene C60 and VOO open an interesting field concerning
      their potential antigenotoxic agents against deleterious side effects of
      chemotherapeutics.

PMID- 30116472
TI  - Upregulation of SIRT1 by Kartogenin Enhances Antioxidant Functions and Promotes
      Osteogenesis in Human Mesenchymal Stem Cells.
AB  - Osteoarthritis is a chronic degenerative joint disease involving both articular
      cartilage and subchondral bone. Kartogenin (KGN) was recently identified to
      improve in vivo cartilage repair; however, its effect on bone formation is
      unknown. The aim of this study was to investigate the effect of KGN on
      antioxidant properties and osteogenic differentiation of bone marrow-derived
      mesenchymal stem cells (BM-MSCs). Human BM-MSCs were treated with KGN at
      concentrations ranging from 10-8 M to 10-6 M. Our results indicated that KGN
      improved cell proliferation and attenuated intracellular reactive oxygen species.
      The levels of antioxidant enzymes and osteogenic differentiation of BM-MSCs were
      enhanced by KGN in a dose-dependent manner. Furthermore, KGN-treated BM-MSCs
      showed upregulation of silent information regulator type 1 (SIRT1) and increased
      phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK),
      indicating that KGN activated the AMPK-SIRT1 signaling pathway in BM-MSCs.
      Inhibition of SIRT1 by nicotinamide reversed the antioxidant effect of KGN on BM
      MSCs and suppressed osteogenic differentiation. In conclusion, our results
      demonstrated that KGN improved intracellular antioxidant properties and promoted
      osteogenic differentiation of BM-MSCs by activating the AMPK-SIRT1 signaling
      pathway. Thus, KGN may have the potential for not only articular cartilage repair
      but also the clinical application of MSCs in bone tissue engineering.

PMID- 30116473
TI  - Intracellular and Intercellular Signalling Mechanisms following DNA Damage Are
      Modulated By PINK1.
AB  - Impaired mitochondrial function and accumulation of DNA damage have been
      recognized as hallmarks of age-related diseases. Mitochondrial dysfunction
      initiates protective signalling mechanisms coordinated at nuclear level
      particularly by modulating transcription of stress signalling factors. In turn,
      cellular response to DNA lesions comprises a series of interconnected complex
      protective pathways, which require the energetic and metabolic support of the
      mitochondria. These are involved in intracellular as well as in extracellular
      signalling of damage. Here, we have initiated a study that addresses how
      mitochondria-nucleus communication may occur in conditions of combined
      mitochondrial dysfunction and genotoxic stress and what are the consequences of
      this interaction on the cell system. In this work, we used cells deficient for
      PINK1, a mitochondrial kinase involved in mitochondrial quality control whose
      loss of function leads to the accumulation of dysfunctional mitochondria,
      challenged with inducers of DNA damage, namely, ionizing radiation and the
      radiomimetic bleomycin. Combined stress at the level of mitochondria and the
      nucleus impairs both mitochondrial and nuclear functions. Our findings revealed
      exacerbated sensibility to genotoxic stress in PINK1-deficient cells. The same
      cells showed an impaired induction of bystander phenomena following stress
      insults. However, these cells responded adaptively when a challenge dose was
      applied subsequently to a low-dose treatment to the cells. The data demonstrates
      that PINK1 modulates intracellular and intercellular signalling pathways,
      particularly adaptive responses and transmission of bystander signalling, two
      facets of the cell-protective mechanisms against detrimental agents.

PMID- 30116474
TI  - Honokiol Protects against Anti-beta1-Adrenergic Receptor Autoantibody-Induced
      Myocardial Dysfunction via Activation of Autophagy.
AB  - Myocardial diseases are prevalent syndromes with high mortality rate. The
      exploration of effective interference is important. Anti-beta1-adrenergic
      receptor autoantibody (beta1-AAB) is highly correlated with myocardial
      dysfunction. The actions and underlying mechanisms of honokiol (HNK) in beta1-AAB
      positive patients await to be unraveled. In this study, we established a rat
      model of beta1-AAB positive with myocardial dysfunction. Cardiac function
      following beta1-AR-ECII administration was analyzed using the VisualSonics Vevo
      770 High-Resolution In Vivo Imaging System. The levels of autophagy-related
      proteins were detected by Western blotting. Our data revealed that HNK reversed
      beta1-AAB-induced effects and protected myocardial tissues from dysfunction.
      After HNK treatment, the cardiac contractile ability increased and the LDH
      activity decreased. HNK attenuated myocardial degeneration. In addition, HNK
      promoted the activation of the AMP-dependent protein kinase/Unc-51-like autophagy
      activating kinase (AMPK/ULK) pathway and activated autophagy. These results
      suggest that HNK protects against beta1-AAB-induced myocardial dysfunction via
      activation of autophagy and it may be a potentially therapeutic compound for
      beta1-AAB-positive myocardial diseases.

PMID- 30116475
TI  - Phenolic Plant Extracts Induce Sirt1 Activity and Increase Antioxidant Levels in
      the Rabbit's Heart and Liver.
AB  - Background: Several dietary phytochemicals potentially regulate the equilibrium
      between oxidant and antioxidant species. The aim of this study was to evaluate
      the effects of Lippia citriodora, Raphanus sativus, and Solanum lycopersicum on
      blood parameters, oxidative/antioxidant status, and SIRT1 activity in the
      rabbit's heart and liver. Methods: Twenty rabbits were divided into 4 groups of 5
      animals each. The control group (CN) received a feed without any additives. One
      intervention group received a supplement containing verbascoside (VB), another
      Raphanus sativus extract (RAP), and lastly lycopene (LYC). Oxidant-antioxidant
      parameters and SIRT1 activity were measured in plasma and in the heart and liver,
      respectively. Results: The treatment with VB, RAP, and LYC resulted in a marked
      improvement in the blood lipid and glycaemic profile in respect to CN. VB was the
      most effective, but all three plant extracts induced a significant reduction in
      oxidant parameters as well as an increase in antioxidant tissue activity and
      vitamin A and E levels. SIRT1 activity was significantly increased in both VB and
      LYC compared to CN, but the increased levels in the VB group were far the
      highest. The multivariate analysis suggests that the benefits of VB, particularly
      the antiglycaemic and antioxidant effects, might be mediated by increasing SIRT1
      activity.

PMID- 30116477
TI  - Protective Effect of Increased Zinc Supply against Oxidative Damage of Sublingual
      Gland in Chronic Exposure to Cadmium: Experimental Study on Rats.
AB  - Cadmium is one of the main chemical pollutants found in the daily environment of
      developed countries. Cigarettes are a significant source of that metal, which
      makes it important in terms of oral cavity health. The aim of this study was to
      determine if increased supply of zinc in chronic exposure to cadmium might
      protect the sublingual gland structure against oxidative damage. The experiment
      took 12 months and was conducted on 72 adult male rats. They were randomized into
      9 groups. Eight groups received cadmium in drinking water (as CdCl2) at 5 or 50
      mg Cd/dm3 and/or zinc (as ZnCl2) at 30 or 60 mg Zn/dm3. The control group
      received regular water. In the sublingual gland of all animal groups, levels of
      oxidative parameters were measured. The oxidative stress index was calculated as
      a TOS/TAS ratio. Cadmium exposure at 5 mg and 50 mg Cd/dm3 induced oxidative
      stress in the sublingual glands of the rats. Cadmium reduced the TAS and GSH
      levels and increased LPO, H2O2, TOS, and OSI. In cadmium exposure conditions,
      increasing the supply of zinc by 79% or 151%, as compared to the standard dietary
      intake of this microelement, completely prevented the reduction of TAS and GSH
      levels and accumulation of LPO, H2O2, and TOS in the examined gland at both
      exposure levels to that metal. The outcome data confirm the protective effect of
      increased zinc intake on the sublingual gland tissue in chronic cadmium exposure.

PMID- 30116476
TI  - Coenzyme Q10 Prevents Senescence and Dysfunction Caused by Oxidative Stress in
      Vascular Endothelial Cells.
AB  - Oxidative damage in endothelial cells is proposed to play an important role in
      endothelial dysfunction and atherogenesis. We previously reported that the
      reduced form of coenzyme Q10 (CoQ10H2) effectively inhibits oxidative stress and
      decelerates senescence in senescence-accelerated mice. Here, we treated human
      umbilical vein endothelial cells (HUVECs) with H2O2 and investigated the
      protective effect of CoQ10H2 against senescence, oxidative damage, and reduction
      in cellular functions. We found that CoQ10H2 markedly reduced the number of
      senescence-associated beta-galactosidase-positive cells and suppressed the
      expression of senescence-associated secretory phenotype-associated genes in H2O2
      treated HUVECs. Furthermore, CoQ10H2 suppressed the generation of intracellular
      reactive oxygen species (ROS) but promoted NO production that was accompanied by
      increased eNOS expression. CoQ10H2 prevented apoptosis and reductions in
      mitochondrial function and reduced migration and tube formation activity of H2O2
      treated cells. The present study indicated that CoQ10H2 protects endothelial
      cells against senescence by promoting mitochondrial function and thus could delay
      vascular aging.

PMID- 30116478
TI  - Isolation and Characterization of NP-POL Nonapeptide for Possible Therapeutic Use
      in Parkinson's Disease.
AB  - Colostrum and milk are the initial mammalian nourishment and rich reservoir of
      essential nutrients for newborn development. Bioactive peptides isolated from
      natural sources, such as colostrum, serve as endogenous regulators and can be
      used as alternative therapeutic agents in the treatment of neurodegenerative
      diseases. One example is the previously unknown NP-POL nonapeptide isolated from
      Colostrinin. In the present study, we investigated a method of NP-POL nonapeptide
      isolation using Bio-Gel P2 molecular sieve chromatography. We showed the
      protective effect of NP-POL on 6-hydroxydopamine- (6-OHDA-) induced neurotoxicity
      using rat adrenal pheochromocytoma (PC12 Tet On) cells. Treatment of PC12 cells
      with NP-POL nonapeptide reduced 6-OHDA-induced apoptosis and caused transient
      phosphorylation of extracellular signal-regulated kinases (ERK 1/2), which were
      shown to promote cell survival. NP-POL nonapeptide also protected neuronal cells
      against oxidative injury induced by 6-OHDA. These results showed a potential use
      of NP-POL in the therapy of Parkinson's disease.

PMID- 30116479
TI  - Antioxidant Status in the Soleus Muscle of Sprague-Dawley Rats in Relation to
      Duodenal-Jejunal Omega Switch and Different Dietary Patterns.
AB  - Background: Obesity and chronic ingestion of lipid-rich meals are related to an
      enhanced oxidative stress (OS). Aims: To examine the influence of duodenal
      jejunal omega switch surgery in combination with different diets on the
      antioxidative status in the soleus muscle of rats. Methods: After 8 weeks on a
      high-fat diet (HF) or control diet (CD), rats underwent duodenal-jejunal omega
      switch (DJOS) or SHAM (control) surgery. After surgery, for the next 8 weeks,
      half of DJOS/SHAM animals were kept on the same diet as before, and half had a
      changed diet. The total superoxide dismutase (SOD), catalase (CAT), glutathione
      peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR)
      activity as well as malondialdehyde (MDA) concentration were measured in the
      soleus of rats. Results: CAT and GPx activity were significantly lower after DJOS
      surgery versus SHAM, regardless of the type of diet. The activity of CAT, SOD,
      GR, CuZnSOD, and GPx was altered in the CD/HF or HF/CD groups. After DJOS, the
      lowest muscle concentration of MDA was observed in the CD/CD group and the
      highest in CD/HF. Conclusions: DJOS surgery significantly decreases the
      antioxidative system in soleus muscles of rats. CD/HF and HF/CD dietary patterns
      lead to an increase in antioxidative activity, while remaining on unchanged diet
      (CD or HF) is associated with a reduced oxidative stress.

PMID- 30116480
TI  - Antioxidant, Anti-Inflammatory, and Microbial-Modulating Activities of
      Nutraceuticals and Functional Foods 2018.

PMID- 30116481
TI  - The Protective Effect of New Compound XH-103 on Radiation-Induced GI Syndrome.
AB  - Background: Radiation-induced intestinal injury is one of the side effects in
      patients receiving radiotherapy. The aim of the present study was to investigate
      the protective effect of XH-103 on radiation-induced small intestinal injury and
      to explore its mechanism. Methods: C57BL/6N mice were irradiated and treated with
      XH-103. Firstly, the survival rate of mice exposed to 9.0 Gy and 11.0 Gy total
      body irradiation (TBI) was examined. Subsequently, at 3.5 d after IR, the small
      intestinal morphological changes were examined by HE. The numbers of crypt cells,
      the villus height, the expression of Ki67 and Lgr5, and the apoptotic cells in
      the intestinal crypts were examined by immunohistochemistry. Furthermore, the
      expression of p53 and Bax was analyzed by WB. Results: Compared to the
      irradiation group, XH-103 improved the mice survival rate, protected the
      intestinal morphology of mice, decreased the apoptotic rate of intestinal crypt
      cells, maintained cell regeneration, and promoted crypt proliferation and
      differentiation. XH-103 also reduced the expression of p53 and Bax in the small
      intestine compared to the IR group. Conclusion: These data demonstrate that XH
      103 can prevent radiation-induced intestinal injury, which is beneficial for the
      protection of radiation injuries.

PMID- 30116483
TI  - Sodium Ferulate Attenuates Lidocaine-Induced Corneal Endothelial Impairment.
AB  - The introduction of intracameral anaesthesia by injection of lidocaine has become
      popular in cataract surgery for its inherent potency, rapid onset, tissue
      penetration, and efficiency. However, intracameral lidocaine causes corneal
      thickening, opacification, and corneal endothelial cell loss. Herein, we
      investigated the effects of lidocaine combined with sodium ferulate, an
      antioxidant with antiapoptotic and anti-inflammatory properties, on lidocaine
      induced damage of corneal endothelia with in vitro experiment of morphological
      changes and cell viability of cultured human corneal endothelial cells and in
      vivo investigation of corneal endothelial cell density and central corneal
      thickness of cat eyes. Our finding indicates that sodium ferulate from 25 to 200
      mg/L significantly reduced 2 g/L lidocaine-induced toxicity to human corneal
      endothelial cells, and 50 mg/L sodium ferulate recovered the damaged human
      corneal endothelial cells to normal growth status. Furthermore, 100 mg/L sodium
      ferulate significantly inhibited lidocaine-induced corneal endothelial cell loss
      and corneal thickening in cat eyes. In conclusion, sodium ferulate protects human
      corneal endothelial cells from lidocaine-induced cytotoxicity and attenuates
      corneal endothelial cell loss and central corneal thickening of cat eyes after
      intracameral injection with lidocaine. It is likely that the antioxidant effect
      of sodium ferulate reduces the cytotoxic and inflammatory corneal reaction during
      intracameral anaesthesia.

PMID- 30116484
TI  - Exposure of Drosophila melanogaster to Mancozeb Induces Oxidative Damage and
      Modulates Nrf2 and HSP70/83.
AB  - Mancozeb (MZ), a manganese- and zinc-containing ethylene-bis-dithiocarbamate, is
      a broad-spectrum fungicide. Harmful effects of this fungicide have been reported
      in nontarget organisms via a not fully understood mechanism. Drosophila
      melanogaster has provided remarkable contributions for toxicological studies.
      This work was aimed at evaluating the biochemical targets and implication of
      oxidative stress in MZ-mediated toxicity in drosophilas. Exposure of flies for
      fifteen days to MZ at 5 and 10 mg/mL through the diet impaired locomotor
      performance and induced fly mortality. In parallel, it caused lipid peroxidation
      and reactive oxygen species (ROS) formation and Mn overload. MZ inhibited
      superoxide dismutase and inducted catalase and glutathione S-transferase
      activities. Nitric oxide and reduced glutathione levels were significantly
      decreased by MZ. Heat shock proteins (HSP70 and HSP83) and Nrf2 mRNA levels were
      significantly augmented in MZ-exposed flies. Our study reinforced the use of
      Drosophila melanogaster as a reliable model for the study of biochemical targets
      of pesticides, and based on our data, MZ induced oxidative damage and Mn
      accumulation in a concentration-dependent manner. An adaptative cellular state
      was inducted by the lower concentration of pesticide, possibly contributing to
      the slighter damage observed.

PMID- 30116485
TI  - The Effects of Potassium Cyanide on the Functional Recovery of Isolated Rat
      Hearts after Ischemia and Reperfusion: The Role of Oxidative Stress.
AB  - This investigation is aimed at examining the effects of pharmacological PostC
      with potassium cyanide (KCN) on functional recovery, gene expression, cytochrome
      c expression, and redox status of isolated rat hearts. Rats were divided into the
      control and KCN groups. The hearts of male Wistar albino rats were retrogradely
      perfused according to the Langendorff technique at a constant perfusion pressure
      of 70 cmH2O. After stabilisation, control hearts were subjected to global
      ischemia (5 minutes), followed by reperfusion (5 minutes), while experimental
      hearts underwent global ischemia (5 minutes) followed by 5 minutes of reperfusion
      with 10 MUmol/L KCN. The following parameters of heart function were measured:
      maximum and minimum rates of pressure development, systolic and diastolic left
      ventricular pressure, heart rate, and coronary flow. Levels of superoxide anion
      radical, hydrogen peroxide, nitrites, and index of lipid peroxidation (measured
      as thiobarbituric acid-reactive substances) were measured in coronary venous
      effluent, and activity of catalase was determined in heart tissue. Expression of
      Bax, Bcl-2, SOD-1, SOD-2, and cytochrome c was studied as well. It was shown that
      expression of Bax, Bcl-2, and SOD-2 genes did not significantly differ between
      groups, while expression of SOD-1 gene and cytochrome c was lower in the KCN
      group. Our results demonstrated that KCN improved the recovery of myocardial
      contractility and systolic and diastolic function, enhanced catalase activity,
      and diminished generation of prooxidants. However, all possible mechanisms and
      potential adverse effects of KCN should be further examined in the future.

PMID- 30116486
TI  - Correlation of Reactive Oxygen Species Levels with Resveratrol Sensitivities of
      Anaplastic Thyroid Cancer Cells.
AB  - Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid malignancy without
      a reliable therapeutic agent. Resveratrol possesses cancer-suppressive effects,
      while its effect(s) on ATC cells remains unknown. Because oxidative damage caused
      by increased reactive oxygen species (ROS) is one of the therapeutic effects of
      anticancer drugs and oxidative stress-caused mitochondria swelling is observed in
      resveratrol-treated cancer cells, the oxidative statuses and their relevance with
      resveratrol sensitivities are elucidated using THJ-16T and THJ-11T ATC cells
      established from two human anaplastic thyroid carcinoma cases. The results
      revealed that resveratrol-treated THJ-16T rather than THJ-11T cells showed
      remarkable growth arrest and extensive apoptosis accompanied with the elevated
      ROS generation and the attenuated superoxide dismutase 2 (SOD2) and catalase
      (CAT) levels. Mitochondrial impairment and the enhanced caspase-9/caspase-3
      activation are found only in resveratrol-sensitive THJ-16T cells. Treatment with
      the antioxidant N-acetylcysteine (NAC) partly attenuated resveratrol-induced ROS
      generation and apoptosis of THJ-16T cells. The levels of resveratrol metabolic
      enzymes (SULT1A1 and SULT1C2) in THJ-16T cells were lower than those in THJ-11T
      cells and therefore reversely related with resveratrol sensitivities of ATC
      cells. Our findings demonstrate the ability of resveratrol to increase ROS
      generation and oxidative-related cellular lesions in resveratrol-sensitive THJ
      16T cells presumably through activating the ROS-mitochondrial signal pathway. The
      levels of SULTs and ROS may reflect the response manners of ATC cells to
      resveratrol.

PMID- 30116487
TI  - Protective Effects of Miswak (Salvadora persica) against Experimentally Induced
      Gastric Ulcers in Rats.
AB  - Gastric ulcers are among the most broadly perceived illnesses affecting
      individuals. Alcohol consumption is the main cause of gastric ulceration. This
      study assessed the protective effects of Salvadora persica (SP) extract against
      ethanol-induced gastric ulcer and elucidated the conceivable underlying
      mechanisms involved. For this purpose, 40 rats were allotted into 4 equal groups
      (control, ethanol- (EtOH-) treated, and SP-treated "SP200 and SP400" groups). The
      control and EtOH-treated groups were given phosphate buffer saline (PBS), and
      both the SP200 and SP400 groups were given SP extract dissolved in PBS at doses
      of 200 and 400 mg/kg b.w., respectively. All treatments were given orally for 7
      constitutive days. On the 8th day, all rats were fasted for 24 h followed by oral
      gavage of PBS in the control group and chilled absolute ethanol solution (5 ml/kg
      b.w.) in the EtOH- and SP-treated groups to induce gastric lesions. One hour
      later, the rats were sacrificed and the stomachs were harvested. Gross and
      microscopic examinations of the EtOH-treated group showed severe gastric
      hemorrhagic necrosis, submucosal edema, destruction of epithelial cells, and
      reduced glycoprotein content at the mucus surface. These pathological lesions
      were defeated by SP extract treatment. Administration of SP extract modulated the
      oxidative stress and augmented the antioxidant defenses. The elevated ethanol
      expressed tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL
      1beta) genes, as well as bcl-2-like protein 4 (Bax) and inducible nitric oxide
      synthase (iNOS), were diminished in the SP-treated group. Curiously, SP extract
      upregulated endothelial nitric oxide synthase (eNOS) and transforming growth
      factor-beta1 (TGF-beta1) gene expression comparable to that of the EtOH-treated
      rats. Aggregately, SP exerted antiulcer activities in ethanol-induced gastric
      ulcer rat models via modulation of oxidant/antioxidant status, mitigation of
      proinflammatory cytokines, and apoptosis, as well as remodeling of both NOS
      isoforms.

PMID- 30116488
TI  - Resistance-Trained Individuals Are Less Susceptible to Oxidative Damage after
      Eccentric Exercise.
AB  - It has been proposed that exercise-induced oxidative stress and adaptations are
      dependent on training status. In this study, we examined the effects of training
      background on free radical generation and adaptations after eccentric exercise.
      Forty volunteers were divided into two groups (trained and untrained) and were
      asked to perform eccentric exercise. Then, their blood samples were collected
      pre, 24, 48, and 72 hours postexercise. Biomarkers indicating oxidative damage
      and the antioxidant profiles of the participants were measured in plasma and
      erythrocyte lysate both spectrophotometrically and chromatographically. The
      results revealed that the untrained group depicted more severe oxidative damage
      (protein carbonyls, malondialdehyde), weaker antioxidant status (reduced
      glutathione, static and capacity oxidation-reduction potential), and weaker
      radical-scavenging activity (superoxide radical scavenging and reducing power)
      compared to the trained participants. Our findings show that trained individuals
      are less susceptible to oxidative damage and suggest that generalized nutritional
      recommendations regarding recovery after exercise should be avoided.

PMID- 30116490
TI  - Nutrients and Diet: A Relationship between Oxidative Stress, Aging, Obesity, and
      Related Noncommunicable Diseases.

PMID- 30116489
TI  - Hepatoprotective Effect of Polysaccharides Isolated from Dendrobium officinale
      against Acetaminophen-Induced Liver Injury in Mice via Regulation of the Nrf2
      Keap1 Signaling Pathway.
AB  - The effect of polysaccharides isolated from Dendrobium officinale (DOP) on
      acetaminophen- (APAP-) induced hepatotoxicity and the underlying mechanisms
      involved are investigated. Male Institute of Cancer Research (ICR) mice were
      randomly assigned to six groups: (1) control, (2) vehicle (APAP, 230 mg/kg), (3)
      N-acetylcysteine (100 mg/kg), (4) 50 mg/kg DOP, (5) 100 mg/kg DOP, and (6) 200
      mg/kg DOP. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
      levels in the serum and glutathione (GSH), malondialdehyde (MDA), catalase (CAT),
      total antioxidant capacity (T-AOC), myeloperoxidase (MPO), and reactive oxygen
      species (ROS) levels in the liver were determined after the death of the mice.
      The histological examination of the liver was also performed. The effect of DOP
      on the Kelch-like ECH-associated protein 1- (Keap1-) nuclear factor erythroid 2
      related factor 2 (Nrf2) signaling pathway was evaluated using Western blot
      analysis and real-time polymerase chain reaction (PCR). The results showed that
      DOP treatment significantly alleviated the hepatic injury. The decrease in ALT
      and AST levels in the serum and ROS, MDA, and MPO contents in the liver, as well
      as the increases in GSH, CAT, and T-AOC in the liver, were observed after DOP
      treatment. DOP treatment significantly induced the dissociation of Nrf2 from the
      Nrf2-Keap1 complex and promoted the Nrf2 nuclear translocation. Subsequently, DOP
      mediated Nrf2 activation triggered the transcription and expressions of the
      glutamate-cysteine ligase catalytic (GCLC) subunit, glutamate-cysteine ligase
      regulatory subunit (GCLM), heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase
      quinone 1 (NQO1) in APAP-treated mice. The present study revealed that DOP
      treatment exerted potentially hepatoprotective effects against APAP-induced liver
      injury. Further investigation about mechanisms indicated that DOP exerted the
      hepatoprotective effect by suppressing the oxidative stress and activating the
      Nrf2-Keap1 signaling pathway.

PMID- 30116491
TI  - Solid Lipid Nanoparticles of Myricitrin Have Antioxidant and Antidiabetic Effects
      on Streptozotocin-Nicotinamide-Induced Diabetic Model and Myotube Cell of Male
      Mouse.
AB  - Type 2 diabetes mellitus (T2DM) may occur via oxidative stress. Myricitrin is a
      plant-derived antioxidant, and its solid lipid nanoparticle (SLN) may be more
      potent. Hence, the present study was conducted to evaluate the effects of
      myricitrin SLN on streptozotocin-nicotinamide- (STZ-NA-) induced T2DM of the
      mouse and hyperglycemic myotube. In this experimental study, cold homogenization
      method was used to prepare SLN. Then, 120 adult male NMRI mice were divided into
      7 groups: control, vehicle, diabetes (received STZ 65 mg/kg 15 min after injected
      NA 120 mg/kg), diabetes + SLN containing myricitrin 1, 3, and 10 mg/kg, and
      diabetes + metformin. For in vitro study, myoblast (C2C12) cell line was cultured
      and divided into 6 groups (n = 3): control, hyperglycemia, hyperglycemia + SLN
      containing myricitrin 1, 3, and, 10 MUM, and hyperglycemia + metformin. After the
      last nanoparticle treatment, plasma samples, pancreas and muscle tissues, and
      myotubes were taken for experimental assessments. Diabetes increased lipid
      peroxidation and reduced antioxidant defense along with the hyperglycemia,
      insulin resistance, and pancreas apoptosis. Hyperglycemia induced oxidative
      stress, antioxidant impairment, and cellular apoptosis. Myricitrin SLN improved
      diabetes and hyperglycemia complications in the in vivo and in vitro studies.
      Therefore, SLN of myricitrin showed antioxidant, antidiabetic, and antiapoptotic
      effects in the mouse and myotube cells.

PMID- 30116492
TI  - Analysis of Plasma MicroRNAs as Predictors and Biomarkers of Aging and Frailty in
      Humans.
AB  - Although circulating microRNAs (miRNAs) can modulate gene expression and affect
      immune system response, little is known about their participation in age
      associated frailty syndrome and sarcopenia. The aim of this study was to
      determine miRNAs as possible biomarkers of age and frailty and their correlation
      with oxidative and inflammatory state in human blood. Three inflammation-related
      miRNAs (miR-21, miR-146a, and miR-223) and one miRNA related with the control of
      melatonin synthesis (miR-483) were analyzed. Twenty-two healthy adults, 34 aged
      robust, and 40 aged fragile patients were selected for this study. The expression
      of plasma miRNAs was assessed by RT-qPCR; plasma cytokines (IL-6, IL-8, IL-10,
      and TNFalpha) were analyzed by commercial kits, and plasma advanced oxidation
      protein products (AOPP) and lipid oxidation (LPO) were spectrophotometrically
      measured. Fragile subjects had higher miR-21 levels than control subjects,
      whereas miR-223 and miR-483 levels increased at a similar extend in both aged
      groups. All cytokines measured increased in aged groups compared with controls,
      without differences between robust and fragile subjects. The fragile group had a
      TNFalpha/IL-10 ratio significantly higher than robust and control groups. Aged
      groups also had higher AOPP and LPO levels than controls. Women presented higher
      AOPP and LPO levels and increased expression of miR-483 compared with men.
      Positive correlations between miR-21 and AOPP and between miR-483 and IL-8 were
      detected. The expression of miR-21 and the TNFalpha/IL-10 ratio were correlated
      positively with the presence of frailty, which suggests that these markers can be
      considered as possible biomarkers for age-related frailty.

PMID- 30116493
TI  - The Associations between Infertility and Antioxidants, Proinflammatory Cytokines,
      and Chemokines.
AB  - The aim of the study was to evaluate the parameters of oxidative stress and
      antioxidant defense in relation to the levels of proinflammatory cytokines and
      chemokines in patients diagnosed with oligozoospermia and asthenozoospermia.
      Based on the basic parameters of the spermogram, the examined group (n = 243) was
      divided into three groups: oligospermic group (sperm count less than 15 * 106/ml)
      consisting of 152 men, astenozoospermic group (less than 40% of progressively
      moving sperm cells) consisting of 142 men, and oligoastenozoospermic group (both
      criteria met) consisting of 90 men. The control group consisted of 103 males with
      normal semen profile according to the WHO criteria. Total superoxide dismutase
      (SOD) activity in seminal plasma and spermatozoa lysate was significantly lower
      by 12% and 22%, respectively, in males with oligospermia than in the control
      group. Analogically, Mn-SOD activity in spermatozoa lysate was significantly
      lower in males with oligospermia, asthenospermia, and oligoasthenospermia by 44%,
      32%, and 45%, respectively. By contrast, CuZn-SOD activity in spermatozoa lysate
      was significantly higher in males with oligospermia by 60%. The activity of
      glutathione peroxidase (GPx) in seminal plasma was also significantly higher in
      males with oligospermia and oligoasthenospermia by 56% and 78%, respectively. The
      level of malondialdehyde (MDA) in seminal plasma was significantly higher in
      males with asthenospermia than in the control group by 12%. By contrast, the
      level of MDA in spermatozoa lysate was significantly lower in males with
      oligospermia, asthenospermia, and oligoasthenospermia by 26%, 20%, and 26%,
      respectively. The level of interleukin- (IL-) 8 in seminal plasma was
      significantly higher in males with asthenospermia and oligoasthenospermia by 64%
      and 67%, respectively. Abnormalities in spermogram, such as oligospermia,
      asthenospermia, and oligoasthenospermia, may be related to a decreased activity
      of Mn-SOD in spermatozoa and increased levels of chemokines in seminal plasma.

PMID- 30116482
TI  - Cellular Stresses and Stress Responses in the Pathogenesis of Insulin Resistance.
AB  - Insulin resistance (IR), a key component of the metabolic syndrome, precedes the
      development of diabetes, cardiovascular disease, and Alzheimer's disease. Its
      etiological pathways are not well defined, although many contributory mechanisms
      have been established. This article summarizes such mechanisms into the
      hypothesis that factors like nutrient overload, physical inactivity, hypoxia,
      psychological stress, and environmental pollutants induce a network of cellular
      stresses, stress responses, and stress response dysregulations that jointly
      inhibit insulin signaling in insulin target cells including endothelial cells,
      hepatocytes, myocytes, hypothalamic neurons, and adipocytes. The insulin
      resistance-inducing cellular stresses include oxidative, nitrosative,
      carbonyl/electrophilic, genotoxic, and endoplasmic reticulum stresses; the stress
      responses include the ubiquitin-proteasome pathway, the DNA damage response, the
      unfolded protein response, apoptosis, inflammasome activation, and pyroptosis,
      while the dysregulated responses include the heat shock response, autophagy, and
      nuclear factor erythroid-2-related factor 2 signaling. Insulin target cells also
      produce metabolites that exacerbate cellular stress generation both locally and
      systemically, partly through recruitment and activation of myeloid cells which
      sustain a state of chronic inflammation. Thus, insulin resistance may be
      prevented or attenuated by multiple approaches targeting the different cellular
      stresses and stress responses.

PMID- 30116495
TI  - The Effect of MitoQ on Aging-Related Biomarkers: A Systematic Review and Meta
      Analysis.
AB  - Mitochondria are metabolically active organelles that produce significant
      reactive oxygen species, linked with aging and degenerative diseases. In recent
      years, particular focus has been put on mitochondria-targeted antioxidants, to
      decrease the concentration of reactive oxygen species and help alleviate the
      accumulation of oxidative damage and associated aging. MitoQ is a mitochondria
      targeted antioxidant of which is reported to support healthy aging. The aim of
      this systematic review is to investigate the effects of MitoQ on oxidative
      outcomes related to the aging process. A predeveloped search strategy was run
      against MEDLINE (Ovid), EMBASE (Ovid), and CINAHL databases, which identified
      10,255 articles of interest, with 27 of these finalised for use after screening.
      Three outcomes had sufficient data to meta-analyse nitrotyrosine concentration
      (190 animals, SMD -0.67, 95% CI (-1.30, -0.05), p = 0.04), membrane potential (63
      animals, MD 11.44, 95% CI (1.28-21.60), p = 0.03), and protein carbonyl
      concentration (182 animals, SMD -0.13, 95% CI (-0.44, 0.18), p = 0.41). MitoQ
      intervention produced a statistically significant reduction in nitrotyrosine
      concentration and increased membrane potential. MitoQ may be of some benefit in
      alleviating oxidative stress related to aging.

PMID- 30116494
TI  - Protective Effect of Rosamultin against H2O2-Induced Oxidative Stress and
      Apoptosis in H9c2 Cardiomyocytes.
AB  - Rosamultin is one of the main active compounds isolated from Potentilla anserina
      L., which belongs to a triterpene compound. Few studies have examined the effect
      of rosamultin on oxidative stress and its molecular mechanism. The aim of this
      present study was to elucidate the protective effect of rosamultin on H2O2
      induced oxidative damage and apoptosis in H9c2 cardiomyocytes and its mechanism.
      The results showed that the pretreatment of rosamultin not only increased cell
      viability but also reduced the release of LDH and CK. Rosamultin inhibited a H2O2
      induced decrease in SOD, CAT, and GSH-Px activities and an increase in MDA
      content. Meanwhile, ROS level, intracellular (Ca2+) fluorescence intensity, and
      apoptosis rate in the rosamultin pretreated group were markedly decreased
      compared with the model group. Rosamultin pretreatment significantly reversed the
      morphological changes and attenuated H2O2-induced apoptosis. Western blot
      analysis showed that rosamultin enhanced the expression of Bcl-2 and pCryAB and
      downregulated the expression of Bax, Cyt-c, Caspase-3, and Caspase-9 expression.
      Additionally, rosamultin might activate PI3K/Akt signal pathways and CryAB
      relative factors. Therefore, we suggest that rosamultin could have the potential
      for treating H2O2-induced oxidative stress injury through its antioxidant and
      antiapoptosis effect.

PMID- 30116496
TI  - Guarana (Paullinia cupana) Extract Protects Caenorhabditis elegans Models for
      Alzheimer Disease and Huntington Disease through Activation of Antioxidant and
      Protein Degradation Pathways.
AB  - Guarana (Paullinia cupana) is largely consumed in Brazil in high energy drinks
      and dietary supplements because of its stimulant activity on the central nervous
      system. Although previous studies have indicated that guarana has some protective
      effects in Parkinson's (PD), Alzheimer's (AD), and Huntington's (HD) disease
      models, the underlying mechanisms are unknown. Here, we investigated the
      protective effects of guarana hydroalcoholic extract (GHE) in Caenorhabditis
      elegans models of HD and AD. GHE reduced polyglutamine (polyQ) protein
      aggregation in the muscle and also reduced polyQ-mediated neuronal death in ASH
      sensory neurons and delayed beta-amyloid-induced paralysis in a caffeine
      independent manner. Moreover, GHE's protective effects were not mediated by
      caloric restriction, antimicrobial effects, or development and reproduction
      impairment. Inactivation of the transcription factors SKN-1 and DAF-16 by RNAi
      partially blocked the protective effects of GHE treatment in the AD model. We
      show that the protective effect of GHE is associated with antioxidant activity
      and modulation of proteostasis, since it increased the lifespan and proteasome
      activity, reduced intracellular ROS and the accumulation of autophagosomes, and
      increased the expression of SOD-3 and HSP-16.2. Our findings suggest that GHE has
      therapeutic potential in combating age-related diseases associated with protein
      misfolding and accumulation.

PMID- 30116497
TI  - Antioxidant and Antisenescence Effects of Bergamot Juice.
AB  - Aging is one of the main risk factor for the onset of cardiovascular diseases;
      one of the possible explanations could be linked to the age-associated
      overproduction of free radicals. This increase of oxidative stress can be
      overcome with a high intake of food antioxidants. In this context, a number of
      studies have been addressed to assess the antiaging potential of natural
      antioxidant compounds. Recently, it has been shown that the juice of bergamot
      (Citrus bergamia Risso et Poiteau), a fruit mostly produced in the Ionian coastal
      areas of Southern Italy (Calabria), is a valuable source of health-promoting
      constituents with, among other, antioxidant properties. In order to investigate
      the potential antiaging effects of this Mediterranean natural antioxidant source,
      bergamot juices of three different cultivars ("fantastico," "femminello," and
      "castagnaro") were herein characterized by the mean of high-performance liquid
      chromatography-photodiode array-electrospray ionization-tandem mass spectrometry.
      Then, juices were investigated for the evaluation of total polyphenolic and
      flavonoid contents, cell-free model antioxidant activities, and in vitro
      antiaging properties on two different cellular models of induced myocardial
      senescence. The best performing juice was also assessed in vivo. The
      phytochemical profiles confirmed that juices were rich in flavonoids, both
      flavone and flavanone glycosides. In addition, two limonoid glycosides were also
      identified in all cultivars. Each cultivar showed different phenolic and
      flavonoid contents. In tube results showed the juice robust antioxidant
      activities that correlate with their phenolic and flavonoid contents. Moreover,
      for the first time, the ability of juice to counteract the chemical-induced
      senescence was here demonstrated in both cellular models. Lastly, the in vivo
      data obtained from mouse hearts evidenced an increase in transcription of genes
      involved in antiaging and antioxidant responses. The overall results suggest that
      bergamot juice exerts antioxidant and antisenescence effects, making it useful
      for nutraceutical purposes.

PMID- 30116498
TI  - Grape Seed Proanthocyanidin Ameliorates Cardiac Toxicity Induced by Boldenone
      Undecylenate through Inhibition of NADPH Oxidase and Reduction in the Expression
      of NOX2 and NOX4.
AB  - The effect of anabolic androgenic steroids on the cardiovascular system is poorly
      understood. Increased production of free radicals is coupled to the
      pathophysiology of many alterations within the circulatory system. The only
      function of the enzyme family NADPH oxidases (NOXs) is the generation of reactive
      oxygen species (ROS). Therefore, this study investigated the beneficial role of
      grape seed proanthocyanidin extract (GSPE) in ameliorating cardiac toxicity
      induced by the anabolic steroid Boldenone in male rats through NOX inhibition and
      reduction in the expression of NOX2 and NOX4. This study was conducted on forty
      male rats which are divided into four groups (normal control, positive control or
      GSPE, Boldenone, and posttreatment Boldenone with GSPE). A significant increase
      in relative body weight, relative heart weight, and hemodynamic parameters, as
      well as serum concentrations of lactate dehydrogenase, creatine kinase, creatine
      kinase-muscle brain, myoglobin, cholesterol, low-density lipoprotein cholesterol,
      risk factor 1/2, K+, and Cl-, in treated rats with Boldenone when compared with
      control. We also noted a significant increase in the levels of cardiac
      malondialdehyde, H2O2 generation in heart tissues, mRNA expression of NOX2 and
      NOX4, and immunoreactivity to proliferating cell nuclear antigen (PCNA).
      Posttreated rats with Boldenone and GSPE ameliorated cardiac toxicity via
      inhibition of NOX and a reduction in alteration of the expression of NOX2, NOX4,
      and PCNA induced by Boldenone. These novel insights into the antioxidative
      activity of GSPE should serve as a basis for the development of improved
      chemopreventive or therapeutic strategies for cardiac toxicity.

PMID- 30116499
TI  - Thymosin beta4 Prevents Oxidative Stress, Inflammation, and Fibrosis in Ethanol-
      and LPS-Induced Liver Injury in Mice.
AB  - Thymosin beta 4 (Tbeta4), an actin-sequestering protein, is involved in tissue
      development and regeneration. It prevents inflammation and fibrosis in several
      tissues. We investigated the role of Tbeta4 in chronic ethanol- and acute
      lipopolysaccharide- (LPS-) induced mouse liver injury. C57BL/6 mice were fed 5%
      ethanol in liquid diet for 4 weeks plus binge ethanol (5 g/kg, gavage) with or
      without LPS (2 mg/kg, intraperitoneal) for 6 hours. Tbeta4 (1 mg/kg,
      intraperitoneal) was administered for 1 week. We demonstrated that Tbeta4
      prevented ethanol- and LPS-mediated increase in liver injury markers as well as
      changes in liver pathology. It also prevented ethanol- and LPS-mediated increase
      in oxidative stress by decreasing ROS and lipid peroxidation and increasing the
      antioxidants, reduced glutathione and manganese-dependent superoxide dismutase.
      It also prevented the activation of nuclear factor kappa B by blocking the
      phosphorylation of the inhibitory protein, IkappaB, thereby prevented
      proinflammatory cytokine production. Moreover, Tbeta4 prevented fibrogenesis by
      suppressing the epigenetic repressor, methyl-CpG-binding protein 2, that
      coordinately reversed the expression of peroxisome proliferator-activated
      receptor-gamma and downregulated fibrogenic genes, platelet-derived growth factor
      beta receptor, alpha-smooth muscle actin, collagen 1, and fibronectin, resulting
      in reduced fibrosis. Our data suggest that Tbeta4 has antioxidant, anti
      inflammatory, and antifibrotic potential during alcoholic liver injury.

PMID- 30116501
TI  - Relationship between Xanthine Oxidoreductase Redox and Oxidative Stress among
      Chronic Kidney Disease Patients.
AB  - Xanthine oxidase (XO), an isoform of xanthine oxidoreductase (XOR), is thought to
      increase the cardiovascular burden among chronic kidney disease (CKD) patients
      via oxidative radical production. Plasma XOR redox, which is characterized by the
      ratio of XO to total XOR, changes under different oxidative conditions associated
      with kidney dysfunction. However, the relationship between plasma XOR redox and
      oxidative stress (OS) is unclear. Thus, we aimed to clarify whether OS is related
      to XOR redox. We used the redox state of human serum albumin (HSA) as a marker to
      investigate the status of OS in CKD patients. HSA is composed of human
      mercaptoalbumin (HMA), which possesses not oxidized cysteine residues, reversibly
      oxidized human nonmercaptoalbumin-1 (HNA-1), and strongly oxidized human
      nonmercaptoalbumin-2 (HNA-2). The subjects included 13 nondialysis patients (7
      males and 6 females) with varying degrees of kidney function. We found that
      f(HMA) was negatively (R = -0.692, P = 0.0071) and f(HNA-1) was positively (R =
      0.703, P = 0.0058) correlated with plasma XO/XOR. f(HNA-2) showed no correlation
      with XO/XOR (R = 0.146, P = 0.6412), indicating that plasma XOR redox is not
      related to the irreversible oxidation of HSA. In conclusion, plasma XOR redox is
      closely related to HSA redox, particularly reversible oxidation of HSA.

PMID- 30116500
TI  - Renoprotective Effect of Platelet-Rich Plasma on Cisplatin-Induced Nephrotoxicity
      in Rats.
AB  - Platelet-rich plasma (PRP) has grown as an attractive biologic instrument in
      regenerative medicine for its powerful healing properties. It is considered as a
      source of growth factors that may induce tissue repairing and improve fibrosis.
      This product has proven its efficacy in multiple studies, but its effect on
      cisplatin-induced nephrotoxicity has not yet been elucidated. The present
      investigation was performed to estimate the protective impact of platelet-rich
      plasma against cisplatin- (CP-) evoked nephrotoxicity in male rats.
      Nephrotoxicity was induced in male Wistar rats by right uninephrectomy followed
      by CP administration. Uninephrectomized rats were assigned into four groups: (1)
      control group, (2) PRP group, (3) CP group, and (4) CP + PRP group. PRP was
      administered by subcapsular renal injection. Renal function, inflammatory
      cytokines, and growth factor level as well as histopathological investigation
      were carried out. Treatment with PRP attenuated the severity of CP-induced
      nephrotoxicity as evidenced by suppressed creatinine, blood urea nitrogen (BUN),
      and N-acetyl glucosaminidase (NAG) levels. Moreover, PRP depressed intercellular
      adhesion molecule-1 (ICAM-1), kidney injury molecule-1 (KIM-1), caspase-3, and
      transforming growth factor-beta 1 (TGF-beta1) levels, while enhanced the
      epidermal growth factor (EGF) level. These biochemical results were reinforced by
      the histopathological investigation, which revealed restoration of normal renal
      tissue architectures. These findings highlight evidence for the possible
      protective effects of PRP in a rat model of CP-induced nephrotoxicity, suggesting
      a new avenue for using PRP to improve the therapeutic index of cisplatin.

PMID- 30116502
TI  - Antagonistic Phenomena in Network Dynamics.
AB  - Recent research on the network modeling of complex systems has led to a
      convenient representation of numerous natural, social, and engineered systems
      that are now recognized as networks of interacting parts. Such systems can
      exhibit a wealth of phenomena that not only cannot be anticipated from merely
      examining their parts, as per the textbook definition of complexity, but also
      challenge intuition even when considered in the context of what is now known in
      network science. Here we review the recent literature on two major classes of
      such phenomena that have far-reaching implications: (i) antagonistic responses to
      changes of states or parameters and (ii) coexistence of seemingly incongruous
      behaviors or properties-both deriving from the collective and inherently
      decentralized nature of the dynamics. They include effects as diverse as negative
      compressibility in engineered materials, rescue interactions in biological
      networks, negative resistance in fluid networks, and the Braess paradox occurring
      across transport and supply networks. They also include remote synchronization,
      chimera states and the converse of symmetry breaking in brain, power-grid and
      oscillator networks as well as remote control in biological and bio-inspired
      systems. By offering a unified view of these various scenarios, we suggest that
      they are representative of a yet broader class of unprecedented network phenomena
      that ought to be revealed and explained by future research.

PMID- 30116504
TI  - Neurocognitive impairment after acute coronary syndrome: Prevalence and
      characterization in a hospital-based cardiac rehabilitation program sample.
AB  - Introduction: Prospective studies have shown the relation between acute coronary
      syndrome (ACS) and neurocognitive dysfunction with prevalence ranging between
      10.51% and 66.8%. The present study aims to determine the prevalence level of
      neurocognitive dysfunction; the relations between sociodemographic, clinical and
      emotional variables and neurocognitive functioning in a sample of ACS patients.
      Methods: The sample comprised of 53 patients engaged in cardiac rehabilitation
      within 3 months after an ACS. Patients with any medical history of
      neuropsychiatric problems prior to the ACS and illiterate subjects were not
      included in the study. Results: The majority of the sample (85%) exhibits some
      degree of cognitive impairment, with 84.8% showing verbal fluency impairment,
      60.3% memory impairment and only 26,4% had language compromised. Neurocognitive
      general functioning was correlated with age. Memory domain was negatively
      correlated with the number of daily smoked cigarettes before the ACS. Verbal
      fluency was influenced by schooling. Language domain was correlated with mean
      diastolic pressure and with the type of profession, visuospatial domain was
      correlated with schooling, number of cardiovascular risk factors, distress,
      anxiety levels and type of ACS. Conclusion: Prevalence rate of neurocognitive
      dysfunction is considerably high. Besides global neurocognitive functioning,
      verbal fluency and memory are the most affected domains. Several variables were
      related to neurocognitive performance: sociodemographic; cardiovascular risk
      factors; clinical; psychological. The underlying mechanisms of neurocognitive
      dysfunction should be further explored.

PMID- 30116503
TI  - Metabolic syndrome and its components among women with polycystic ovary syndrome:
      a systematic review and meta-analysis.
AB  - Introduction: The objectives of this study were to provide an estimate of the
      prevalence of metabolic syndrome (MetS ) and its components among women with
      PCOS; and calculate the odds ratio (OR) for MetS (using different definitions of
      MetS) in women with PCOS, compared to healthy controls. Methods: All of the
      relevant databases were used to search for appropriate articles that were
      published during the period 2003-2016. We included observational studies (cross
      sectional, comparative cross-sectional) among women who met the inclusion
      criteria. The random-effect models were used to pool the prevalence of MetS and
      its components among PCOS women. This model was also applied to the pooled OR
      assessing the association between MetS and PCOS. Results: The pooled prevalence
      of MetS among PCOS women was found to be 26.30% (95% CI: 23.68-28.93), but varied
      from 7.10% (95% CI: 1.64-12.56) to 37.50% (95% CI: 28.84-46.16), depending upon
      the diagnostic criteria used. Low high-density lipoprotein cholesterol (HDL) -
      61.87% (95% CI: 53.31-70.43) and high waist circumference (WC)- 52.23% (95% CI:
      43.84-60.61) were the most common components of MetS in PCOS women. Compared to
      healthy controls, the overall pooled (OR) of MetS in PCOS patients was 2.09 (95%
      CI: 1.67-2.60), but this ranged from 0.31 (95% CI: 0.13-0.74) to 4.69 (95% CI:
      2.09-10.52), depending upon the diagnostic criteria used. Conclusion: Women with
      PCOS had a much higher prevalence of MetS than was found among the healthy
      controls. Furthermore, as low HDL and high WC were the most common components of
      MetS in PCOS women, these two components specifically need to be addressed in
      prevention strategies.

PMID- 30116505
TI  - Prevalence of cardiometabolic risk factors in a nationally representative sample
      of Iranian children and adolescents: the CASPIAN-V Study.
AB  - Introduction: This study presents the prevalence of cardiometabolic risk factors
      in a nationally representative sample of Iranian children and adolescents.
      Methods: This multi-centric study was conducted in 2015 among 4200 students aged
      7-18 years. They were selected by multistage cluster sampling from 30 provinces
      of Iran. Anthropometric indices, biochemical and clinical parameters were
      measured. Results: The mean of weight, height, waist circumference (WC), systolic
      blood pressure (SBP), diastolic blood pressure (DBP), and fasting blood glucose
      (FBG) was higher in boys than in girls (P < 0.05). The mean of triglyceride (TG),
      total cholesterol (TC) and low-density lipoprotein (LDL) levels were higher in
      girls than in boys (P < 0.05). The mean of weight, height, WC, SBP, DBP, alanine
      transaminase (ALT) and body mass index (BMI) was higher in urban than in rural
      residents (P < 0.05). Overall, 16.1%, 9.4% and 11.4% were underweight, overweight
      and obese. Abdominal obesity was documented in 21.6% of boys and 20.5% of girls.
      Low HDL-C was the most prevalent abnormality of lipid profile (29.5%) followed by
      high serum TGs (27.7%). Low HDL-C was more prevalent in boys than in girls (32.7%
      vs. 26%, respectively, P < 0.05). Prevalence of obesity and overweight were
      higher in girls than in boys (P < 0.05). The prevalence of obesity and
      overweight, abdominal obesity, and low HDL-C were higher in urban than in rural
      residents (P < 0.05). Conclusion: We found considerably high prevalence of some
      cardiometabolic risk factors including overweight and obesity, low HDL-C and
      hypertriglyceridemia in Iranian children and adolescents. The current findings
      underscore the necessity of intensifying health interventions for primordial and
      primary prevention of non-communicable diseases from early life.

PMID- 30116506
TI  - Complete inhibition of phosphatase and tensin homolog promotes the normal and
      oxygen-glucose deprivation/reperfusion-injured PC12 cells to cell death.
AB  - Introduction: Lipid phosphatase and tensin homolog deleted from chromosome 10
      (PTEN) antagonizes phosphoinositide 3-kinase (PI3K)/AKT cell survival pathway.
      The effect of PTEN inhibitors has been rarely examined on cell survival following
      reperfusion injury. In this study, we investigated the neuroprotective effect of
      SF1670, as a new PTEN inhibitor, on an in vitro stroke-like model. Methods: PC12
      cells were exposed to oxygen-glucose deprivation/reperfusion (OGD/R). The cells
      were treated in five conditions as follows: normoxic normoglycemic (NO/NG); 60
      minutes OGD; 60 minutes OGD and 6 h reperfusion (OGD/R); OGD/R treated with 10 uM
      SF1670 (OGD/R-SF), and NO/NG treated with 10 uM SF1670 (NO/NG-SF). Then,
      phosphorylation levels of AKT, P38 in PC12 cells were measured by immunoblotting.
      The cell viability was also determined by colorimetric assay. Results: The
      results of immunoblotting revealed that following OGD/R the levels of phospho-AKT
      (p-AKT) significantly decreased, compared to NO/NG cells (P < 0.05). However, the
      ratio of p-AKT/total AKT significantly increased in the presence of SF1670 in the
      OGD/R-SF group, compared to the OGD/R condition. On the other hand, SF1670
      significantly reduced the p-P38 MAPK and p-JNK levels, compared to OGD/R cells.
      Moreover, cell viability significantly decreased in the OGD and OGD/R condition
      compared to NO/NG cells. Surprisingly, SF-treated cells (OGD/R-SF and NO/NG-SF
      group) showed low cell viability compared to NO/NG condition. Conclusion:
      Overall, our results demonstrated that complete inhibition of phosphatase
      activity of PTEN not only did not exhibit neuroprotective effect but also
      promoted PC12-deprived cells to death.

PMID- 30116507
TI  - The effect of kidney transplantation on speckled tracking echocardiography
      findings in patients on hemodialysis.
AB  - Introduction: Cardiac dysfunction is a major cause of morbidity and mortality in
      patients with end-stage renal disease (ESRD). Previous studies have shown that
      kidney transplantation can reverse some of the gross changes in the myocardial
      structure such as left ventricular ejection fraction (LVEF) and volumes. Whether
      kidney transplantation can reverse the subtle and early myocardial changes in
      ESRD patients who do not suffer from gross alternations in myocardial function is
      not yet studied. The aim of this study was to answer this question. Methods: We
      followed 25 patients with ESRD at baseline that all of them had a kidney
      transplant and were reassessed 1 month after the transplantation. Conventional
      and speckle tracking echocardiography (STE)was done at baseline and 1 month after
      kidney transplantation in patients. Results: LV hypertrophy was the most
      prevalent finding at baseline (58%), followed by diastolic dysfunction (53%).
      Kidney transplantation significantly improved the ejection fraction (EF)
      (treatment effect = 4.23 +/- 2.06%; P = 0.046) and apical 4-chamber strain
      (treatment effect = -0.89 +/- 0.37%; P = 0.021) in the patients. It also reduced
      the LV mass index (treatment effect = -73.82 +/- 11.6; P < 0.001) and relative
      wall thickness (treatment effect = -0.056+/-0.023; P = 0.021). Other variables
      including global longitudinal strain and diastolic dysfunction were not improved
      significantly. Conclusion: STE may show early improvements in myocardial function
      1 month after renal transplantation.

PMID- 30116508
TI  - High protein diets do not affect anthropometric indexes and cardiometabolic risk
      factors among children with excess weight: A randomized controlled trial.
AB  - Introduction: Limited information exists regarding the effects of high protein
      (HP) diets on cardiovascular disease (CVD) risk factors among overweight and
      obese children. Our aim was to determine the effects of an HP diet on
      anthropometric indexes and CVD risk factors among overweight and obese children.
      Methods: In a parallel randomized controlled trial, we recruited 50 overweight
      and obese children, aged 6-11 years, for a 10 week HP or control diet (protein,
      carbohydrate, fat: 25%, 45%, 30% in the HP diet vs. 15%, 55%, 30% in the control
      diet, respectively). Fasting blood glucose (FBG) serum insulin levels, lipid
      profiles, systolic and diastolic blood pressure (SBP and DBP), and anthropometric
      measurements were assessed using standard guidelines. Results: 86% of children
      completed the trial. Percent changes (PC) for anthropometric and biochemical
      variables were not significantly different between the two groups. The PC of
      serum triglyceride (TG) level was significantly decreased in the HP group
      compared to in the control group (PC: -10.16+/-4.30% vs.12.11+/-7.80%; P = 0.01)
      in the crude model, but not in the adjusted model. For other variables, we did
      not find any significant differences between the HP group and the controls.
      Conclusion: In the present study, we did not find any significant effect of
      adherence to an HP diet in improving anthropometric measurements or other CVD
      risk factors among obese and overweight children.

PMID- 30116511
TI  - Large de novo ascending aortic thrombus successfully treated with
      anticoagulation.
AB  - An ascending aortic thrombus is a rare source for embolic transient ischemic
      attack (TIA) or stroke without an associated aortic pathology. Here we describe a
      case of a patient who presented with generalized symptoms of headache and fatigue
      who, on subsequent work-up , was found to have an ascending aortic thrombus with
      no obvious associated aortic pathology, and was successfully treated with
      apixaban, a newer direct oral anticoagulant.

PMID- 30116509
TI  - Subjective correlates of stress management in outpatient cardiac rehabilitation:
      the predictive role of perceived heart risk factors.
AB  - Introduction: The causal attributions and perceived risk factors can affect
      patients' health behaviors. Therefore, the present study aimed to assess (i) the
      effect of an outpatient cardiac rehabilitation (CR) program on perceived heart
      risk factors (PHRFs) and on psychological stress, and (ii) the role of changes of
      PHRFs at pre-post CR in predicting changes in psychological stress. Methods: In
      this longitudinal study, 110 CR patients were assessed from June to November 2016
      in a hospital in Iran. Perceived heart risk factors and perceived stress were
      investigated using the PHRFs scale and the Depression, Anxiety, Stress Scale-21,
      respectively. PHRFs and DASS-21 Stress scale scores were compared before and
      after 26 sessions of exercise-based CR through paired sample t-tests. In
      addition, we investigated the effect of PHRF's change scores on DASS-21 Stress
      scale scores using linear regression analysis. Results: Results showed that CR
      has a little impact in improving the patients' perception of heart risk factors,
      However, CR is significantly effective in reducing stress (P < 0.05). Regression
      analysis evidenced that improvements in patients' perception of risk factors can
      significantly predict a reduction in psychological stress (P = 0.030). The model
      explained 11.2% of the variance in the results. Conclusion: PHRFs appear to be
      significant predictive components of CR's stress reduction. Practitioners should
      focus on patients' perception of risk factors to facilitate stress management in
      CR program.

PMID- 30116510
TI  - Role of plasma levels of CA-125 in predicting outcome of primary PCI after acute
      myocardial infarction in male patients.
AB  - Introduction: Cancer antigen 125 (CA-125) is a tumor marker of ovarian cancer,
      which has shown to be increased in different cardiovascular diseases. Although
      the prognostic role of CA-125 in heart failure and coronary heart disease is well
      established, there is little known about its role in acute myocardial infarction
      (AMI). In this study we aimed to evaluate the serum levels of CA-125 in patients
      with AMI and its prognostic role in evaluating the in-hospital outcome of AMI.
      Methods: We evaluated 120 male patients with AMI and 120 male normal subjects. CA
      125 levels were measured upon the patient's admission to hospital. The in
      hospital major adverse cardiac events (MACE) and its predictors were also
      recorded for AMI patients. Results: CA-125 levels were significantly higher in
      AMI patients compared to normal subjects (7.99+/-6.83 vs. 5.70+/-4.62, P =
      0.003). We found significant positive correlations between CA-125 levels with
      creatine kinase-MB (CKMB) (r=0.621, P < 0.001) and CTnI (r=0.491, P < 0.001). The
      in-hospital MACE was observed in 19 cases (15.8%). Patients with MACE had
      significantly higher value of CA-125, CKMB and CTnI and lower LVEF compared to
      patients without MACE. CKMB (OR=0.967, 95% CI [0.943-0.991], P = 0.007) and CA
      125 levels (OR=0.821, 95% CI [0.688-0.979], P = 0.02) were independent predictors
      of MACE. Conclusion: Serum CA-125 levels are significantly higher in male
      patients with AMI compared to normal subjects and have a significant role in
      predicting in-hospital MACE after AMI. In patients with higher CA-125 more
      aggressive treatment and close observation should be performed in order to reduce
      the possible adverse outcomes.

PMID- 30116512
TI  - Aortic root replacement and valvuloplasty in a woman with severe pectus
      excavatum.
AB  - We describe a case of a 43-year old woman with Marfan's syndrome, tricuspid valve
      regurgitation and severe pectus excavatum who required an aortic root replacement
      and valvuloplasty for an ascending aortic aneurism with aortic valve
      regurgitation and tricuspid valve regurgitation. There was a severe angulation of
      the sternum which was close to 1.5 cm to the column vertebrae. Such cases are
      quite rare and always a challenge for surgeons to achieve adequate exposure of
      the heart and prevent excessive cardiac compression. We present our access, a
      safe and efficient exposure of the heart in order to achieve the best outcome.

PMID- 30116513
TI  - Different Dosages of Corticosteroid and Routes of Administration in Mandibular
      Third Molar Surgery: a Systematic Review.
AB  - Objectives: The objective of the present systematic review was to test the
      hypothesis of no difference in facial swelling, pain and trismus after surgical
      removal of mandibular third molar with different dosages of corticosteroids and
      administration routes. Material and Methods: A MEDLINE (PubMed), Embase database
      and Cochrane Library search in combination with a hand-search of relevant
      journals was conducted by including randomized controlled trials published in
      English until 1st December 2017. Results: Seven studies fulfilled the inclusion
      criteria. Considerable variation in the included studies prevented meta-analysis
      from being performed. Preoperative submucosal injection of corticosteroids
      significantly diminishes facial swelling, pain and trismus compared with placebo.
      However, different dosages of corticosteroid and administration routes reveal
      contrary results indicating that administration of a higher dosage of
      corticosteroids do not necessarily cause a further decrease in facial swelling,
      pain and trismus. Conclusions: Consequently, the optimal dosage of
      corticosteroids and administration route for diminishing postsurgical morbidity
      and improve quality of life after surgical removal of mandibular third molar is
      presently unknown. Therefore, further well-designed randomized clinical trials
      including a standardised protocol, patient-reported outcome measures and three
      dimensional analysis of facial swelling is needed.

PMID- 30116514
TI  - Prosthetic Rehabilitation of the Partially Edentulous Atrophic Posterior Mandible
      with Short Implants (<= 8 mm) Compared with the Sandwich Osteotomy and Delayed
      Placement of Standard Length Implants (> 8 mm): a Systematic Review.
AB  - Objectives: Test the hypothesis of no difference in prosthetic rehabilitation of
      the partially edentulous atrophic posterior mandible with short implants (<= 8
      mm) compared with the sandwich osteotomy and delayed placement of standard
      lengths implants (> 8 mm). Material and Methods: A MEDLINE (PubMed), Embase and
      Cochrane library search in combination with a hand-search was conducted by
      including studies published in English. No year of publication restriction was
      applied. Results: Six randomized controlled trials characterized by low or
      moderate risk of bias fulfilled the inclusion criteria. There were no
      statistically significant differences (P > 0.05) in the survival rate of
      suprastructures and implants between the two treatment modalities after one year.
      Sandwich osteotomy and delayed implant placement demonstrated statistically
      significant higher long-term peri-implant marginal bone loss as well as
      biological and technical complications compared with short implants (P < 0.0001).
      Moreover, patients significantly favoured prosthetic rehabilitation with short
      implants (P < 0.0001). Conclusions: Short implants and the sandwich osteotomy
      with delayed placement of standard length implants appear to result in
      predictable outcomes in terms of high survival rate of suprastructures and
      implants after prosthetic rehabilitation of the partially edentulous atrophic
      posterior mandible. However, further long-term randomized controlled trials
      assessing donor site morbidity, an economic perspective, professional and patient
      related outcome measures with the two treatment modalities are needed before
      definite conclusions can be provided about the beneficial use of short implants
      for prosthetic rehabilitation of the partially edentulous atrophic posterior
      mandible compared with the sandwich osteotomy and delayed placement of standard
      length implants.

PMID- 30116515
TI  - Use of Autologous Stem Cells for the Regeneration of Periodontal Defects in
      Animal Studies: a Systematic Review and Meta-Analysis.
AB  - Objectives: To overview preclinical animal trials and quantify the effect size
      that stem cell therapy has on the regeneration of periodontal tissue complex.
      Material and Methods: A systematic MEDLINE (PubMed) online library search was
      conducted for preclinical animal studies in vivo , using autologous periodontal
      ligament, dental pulp, cementum, alveolar periosteal, gingival margin or adipose
      stem cell types for periodontal tissue complex regeneration purposes. Studies had
      to be published between 2007.09.01 and 2017.09.01 in the English language.
      Results: Online library search yielded 2099 results. After the title, abstract
      and full-text screening ten studies fit inclusion criteria and were pooled into
      meta-analysis. Overall the stem cell regenerative therapy had a statistically
      significant positive influence on the periodontal tissue regeneration when
      compared to the control groups. The biggest influence was made to the
      regeneration of cementum (standardised mean difference [SMD] 2.25 [95% confidence
      interval (CI) = 1.31 to 3.2]) while the smallest influence was made to the
      alveolar bone (SMD 1.47 [95% CI = 0.7 to 2.25]) the effect size for periodontal
      ligament regeneration was (SMD 1.8 [95% CI = 1 to 2.59]). Subgroup analysis
      showed statistically significant (P < 0.05) differences between different cell
      types in the alveolar bone and cementum regeneration groups and in alveolar bone
      group in relation to scaffold materials. Conclusions: Stem cell therapy has a
      positive impact on periodontal tissue complex regeneration. Such therapy has the
      biggest influence on cementum regeneration meanwhile alveolar bone regeneration
      is influenced by the least amount. However more and less diverse preclinical
      studies are needed to have a greater statistical power in future meta-analyses.

PMID- 30116516
TI  - Diffusion-Weighted Magnetic Resonance Imaging in Maxillary Sinuses Inflammatory
      Diseases: Report of Three Cases and Literature Review.
AB  - Background: Magnetic resonance imaging is considered a preferable imaging
      examination in the diagnosis of inflammatory maxillary sinus disease and can
      provide precise sinonasal characterization. Diffusion-weighted magnetic resonance
      imaging and apparent diffusion coefficient are complementary magnetic resonance
      imaging tools that can be applied to the differentiation of sinus diseases. In
      this report, 3 cases of inflammatory maxillary sinus diseases imaging findings
      considering diffusion-weighted magnetic resonance imaging features were
      described. Additionally, a literature review considering the use of diffusion
      weighted magnetic resonance imaging in inflammatory lesions is provided. Methods:
      The cases reported were: presence of air-fluid levels, mucosal thickening and a
      mucous retention cyst. Conventional magnetic resonance imaging and apparent
      diffusion coefficient (ADC) maps, with ADC values were demonstrated. In the
      literature review, the studies considering inflammatory lesions were detailed, as
      well as ADC values established by investigators. Results: ADC values for presence
      of air-fluid levels, mucosal thickening and mucous retention cyst were
      respectively: 1.99 x 10-3 mm2/s; 1.83 x 10-3 mm2/s; 2.05 x 10-3 mm2/s.
      Conclusions: It was observed that apparent diffusion coefficient values from the
      inflammatory lesions described in this report were different and apparent
      diffusion coefficient may be useful in the differentiation of these maxillary
      sinus alterations. Further larger sample investigations considering apparent
      diffusion coefficient values focusing in inflammatory lesions are recommended.
      The lack of studies considering the use of diffusion-weighted magnetic resonance
      imaging on inflammatory diseases diagnostic was the major limitation to the
      literature review.

PMID- 30116517
TI  - Non-surgical Treatment of Condylar Fracture in an 11-Year-Old Patient: a Case
      Report.
AB  - Background: Mandibular condylar fractures commonly occur after trauma and account
      for 25 to 35% of all mandibular fractures; its appropriate therapy still remains
      a point of controversy in children. The purpose of this paper is to describe the
      treatment of an 11-years-old male patient affected by neck-condylar fracture as
      result of trauma in evolutive age. Methods: No surgical treatment was performed.
      A functional therapy was applied with a jaw splint. A closed treatment for
      mandibular condyle fractures was preferred because the amount of condylar
      displacement wasn't considerable. Results: The early treatment with functional
      therapy generated a functional adaptation of the condyle in the glenoid fossa and
      a normal mandibular function. After a 12-month follow-up the fracture resolution
      and an optimal condylar position were recorded. Conclusions: The current case
      report and literature review showed that non-surgical therapy of neck-condylar
      fracture in a child with lower resin splint can restore mandibular movements and
      aesthetics. Facial growth after one year treatment resulted normal. A
      conservative treatment may be appropriate for children in selected cases with
      minimally displaced condyle.

PMID- 30116519
TI  - Retrospective audit of 957 consecutive 18F-FDG PET-CT scans compared to CT and
      MRI in 493 patients with different histological subtypes of bone and soft tissue
      sarcoma.
AB  - Background: The use of 18F-FDG PET-CT (PET-CT) is widespread in many cancer types
      compared to sarcoma. We report a large retrospective audit of PET-CT in bone and
      soft tissue sarcoma with varied grade in a single multi-disciplinary centre. We
      also sought to answer three questions. Firstly, the correlation between sarcoma
      sub-type and grade with 18FDG SUVmax, secondly, the practical uses of PET-CT in
      the clinical setting of staging (during initial diagnosis), restaging (new
      baseline prior to definitive intervention) and treatment response. Finally, we
      also attempted to evaluate the potential additional benefit of PET-CT over
      concurrent conventional CT and MRI. Methods: A total of 957 consecutive PET-CT
      scans were performed in a single supra-regional centre in 493 sarcoma patients
      (excluding GIST) between 2007 and 2014. We compared, PET-CT SUVmax values in
      relation to histology and FNCCC grading. We compared PET-CT findings relative to
      concurrent conventional imaging (MRI and CT) in staging, restaging and treatment
      responses. Results: High-grade (II/III) bone and soft tissue sarcoma correlated
      with high SUVmax, especially undifferentiated pleomorphic sarcoma,
      leiomyosarcoma, translocation induced sarcomas (Ewing, synovial, alveolar
      rhabdomyosarcoma), de-differentiated liposarcoma and osteosarcoma. Lower SUVmax
      values were observed in sarcomas of low histological grade (grade I), and in rare
      subtypes of intermediate grade soft tissue sarcoma (e.g. alveolar soft part
      sarcoma and solitary fibrous tumour). SUVmax variation was noted in malignant
      peripheral nerve sheath tumours, compared to the histologically benign plexiform
      neurofibroma, whereas PET-CT could clearly differentiate low from high-grade
      chondrosarcoma. We identified added utility of PET-CT in addition to MRI and CT
      in high-grade sarcoma of bone and soft tissues. An estimated 21% overall
      potential benefit was observed for PET-CT over CT/MRI, and in particular, in
      'upstaging' of high-grade disease (from M0 to M1) where an additional 12% of
      cases were deemed M1 following PET-CT. Conclusions: PET-CT in high-grade bone and
      soft tissue sarcoma can add significant benefit to routine CT/MRI staging.
      Further prospective and multi-centre evaluation of PET-CT is warranted to
      determine the actual predictive value and cost-effectiveness of PET-CT in
      directing clinical management of clinically complex and heterogeneous high-grade
      sarcomas.

PMID- 30116518
TI  - Impact of surface topography and coating on osteogenesis and bacterial attachment
      on titanium implants.
AB  - Titanium (Ti) plays a predominant role as the material of choice in orthopaedic
      and dental implants. Despite the majority of Ti implants having long-term
      success, premature failure due to unsuccessful osseointegration leading to
      aseptic loosening is still too common. Recently, surface topography modification
      and biological/non-biological coatings have been integrated into
      orthopaedic/dental implants in order to mimic the surrounding biological
      environment as well as reduce the inflammation/infection that may occur. In this
      review, we summarize the impact of various Ti coatings on cell behaviour both in
      vivo and in vitro. First, we focus on the Ti surface properties and their effects
      on osteogenesis and then on bacterial adhesion and viability. We conclude from
      the current literature that surface modification of Ti implants can be generated
      that offer both osteoinductive and antimicrobial properties.

PMID- 30116520
TI  - Protease resistance of food proteins: a mixed picture for predicting
      allergenicity but a useful tool for assessing exposure.
AB  - Background: Susceptibility to pepsin digestion of candidate transgene products is
      regarded an important parameter in the weight-of-evidence approach for
      allergenicity risk assessment of genetically modified crops. It has been argued
      that protocols used for this assessment should better reflect physiological
      conditions encountered in representative food consumption scenarios. Aim: To
      evaluate whether inclusion of more physiological conditions, such as sub-optimal
      and lower pepsin concentrations, in combination with pancreatin digestion,
      improved the performance of digestibility protocols used in characterization of
      protein stability. Methods: Four pairs of established allergens and their related
      non/weakly-allergenic counterparts (seed albumins, muscle tropomyosins, plant
      lipid transfer proteins [LTP] and collagens) plus fish parvalbumin, were
      subjected to nine combinations of pH (1.2-2.5-4.0) and pepsin-to-protein ratio
      (PPR: 10-1-0.1 U/ug) for pepsin digestion, followed by pancreatin digestion in
      the presence of bile salts. Digestion was monitored by SDS-PAGE in conjunction
      with Coomassie staining and immunoblotting using rabbit antisera and human IgE.
      Results: At pH 4.0 and at PPR 0.1 most proteins, both allergen and non-allergen,
      were highly resistant to pepsin. Under conditions known to favor pepsin
      proteolysis, the established major allergens Ara h 2, Pru p 3 and Pen a 1 were
      highly resistant to proteolysis, while the allergen Cyp c 1 was not. However,
      this resistance to pepsin digestion only made Ara h 2 and to a lesser extent Pen
      a 1 and Pru p 3 stand out compared to their non-allergenic counterparts. Largely
      irrespective of preceding pepsin digestion conditions, pancreatin digestion was
      very effective for all tested proteins, allergens and non-allergens, except for
      Cyp c 1 and bovine collagen. Conclusions: Sub-optimal pH, low pepsin-to protein
      ratio, and sequential pepsin and pancreatin digestion protocols do not improve
      the predictive value in distinguish allergens from non-allergens. Digestion
      conditions facilitating such distinction differ per protein pair.

PMID- 30109018
TI  - Laboratory growth of denitrifying water column microbial consortia from deep-sea
      shipwrecks in the northern Gulf of Mexico.
AB  - Background: Shipwrecks serve as a rich source for novel microbial populations
      that have largely remained undiscovered. Low temperatures, lack of sunlight, and
      the availability of substrates derived from the shipwreck's hull and cargo may
      provide an environment in which microbes can develop unique metabolic
      adaptations.   Methods: To test our hypothesis that shipwrecks could influence
      the microbial population involved in denitrification when a consortium is grown
      in the laboratory, we collected samples proximate to two steel shipwrecks in the
      northern Gulf of Mexico. Then under laboratory conditions, we grew two
      independent denitrifying microbial consortia. Each consortium was grown by using
      the BART assay system and analyzed based on growth kinetics, ion chromatography
      and 16S amplicon sequencing. Results: Both denitrifying consortia were different
      from each other based on varied growth profiles, rates of nitrate utilization and
      16S amplicon sequencing. Conclusions: Our observations conclude that the
      laboratory grown water column microbial consortia from deep-sea shipwrecks in the
      Gulf of Mexico are able to undergo aggressive denitrification.

PMID- 30109017
TI  - Best practice data life cycle approaches for the life sciences.
AB  - Throughout history, the life sciences have been revolutionised by technological
      advances; in our era this is manifested by advances in instrumentation for data
      generation, and consequently researchers now routinely handle large amounts of
      heterogeneous data in digital formats. The simultaneous transitions towards
      biology as a data science and towards a 'life cycle' view of research data pose
      new challenges. Researchers face a bewildering landscape of data management
      requirements, recommendations and regulations, without necessarily being able to
      access data management training or possessing a clear understanding of practical
      approaches that can assist in data management in their particular research
      domain. Here we provide an overview of best practice data life cycle approaches
      for researchers in the life sciences/bioinformatics space with a particular focus
      on 'omics' datasets and computer-based data processing and analysis. We discuss
      the different stages of the data life cycle and provide practical suggestions for
      useful tools and resources to improve data management practices.

PMID- 30109027
TI  - Morphology and performance of polyvinyl chloride membrane modified with Pluronic
      F127.
AB  - Background: Attempts to modify the morphology of membrane for application in
      industrial separation are being undertaken by many researchers. The present study
      discusses the morphological modification of polyvinyl chloride (PVC) membrane by
      combining the hydrophilic surfactant Pluronic F127 (PF127) in a polymer solution
      to improve the performance of the membrane.  Method: The membrane is formed using
      the non-solvent induced-phase separation (NIPS) method. PF127 is added to the
      membrane solution as a membrane modifying agent. The effects of the surfactant
      concentration in the dope solution on the permeability of pure water, solute
      rejection, hydrophilic characteristics, and membrane morphology are investigated.
      Results: Higher concentrations of PF127 had a significant effect on the
      permeability of pure water. The highest membrane permeation was 45.65 l/m
      2.hr.atm with the addition of 7% PF127 additive. Conclusion: PF127 is
      successfully proposed as a membrane pore-forming agent in this work; the blending
      of this additive in appropriate amounts in the polymer solution is adequate to
      improve the performance of the PVC membrane.

PMID- 30116524
TI  - Recruitment of sublingual microcirculation using handheld incident dark field
      imaging as a routine measurement tool during the postoperative de-escalation
      phase-a pilot study in post ICU cardiac surgery patients.
AB  - Background: Management of tissue perfusion following cardiac surgery is a
      challenging task where common clinical parameters do not reflect microcirculatory
      dysfunction. Heterogeneity in blood flow perfusion and abnormalities in capillary
      density characterize microcirculatory dysfunction. The restoration of a normal
      microcirculation may become a novel target for therapy in the future in addition
      to macrocirculatory parameters. The aim of this study is to determine how the
      sublingual microcirculatory parameters vary at the bedside in post-cardiac
      surgery patients which underwent diuretic therapy to correct fluid overload.
      Methods: In this prospective observational pilot study, video clips of sublingual
      microcirculation in post-cardiac surgery patients receiving furosemide and/or
      spironolactone to achieve normal fluid balance were recorded using Cytocam-IDF
      imaging. Data was obtained on the first (T0), second (T1), and third (T2) day
      after the patients left the intensive care unit (ICU). Measurements were analyzed
      off-line to obtain the following microcirculatory parameters: total vessel
      density (TVD), microcirculatory flow index (MFI), proportion of perfused vessel
      (PPV), and perfused vessel density (PVD). Macrocirculatory parameters and body
      weight were also collected at these time points. Results: Ninety measurements
      were performed in ten post ICU cardiac surgery patients. Thirteen measurements
      were excluded due to quality reasons; these excluded measurements were spread
      across the patients and time points, and there was no loss of patients or time
      points. An increase in TVD was observed from T0 to T1 (20 +/- 2.7 to 24 +/- 3.2
      mm/mm2; p = 0.0410) and from T0 to T2 (20 +/- 2.7 to 26 +/- 3.3 mm/mm2; p =
      0.0005). An increase in PVD was present from T0 to T1 (19 +/- 2.3 to 24 +/- 3.5
      mm/mm2; p = 0.0072) and from T0 to T2 (19 +/- 2.3 to 26 +/- 3.4 mm/mm2, p =
      0.0008). Fluid overload was assessed through a positive cumulative fluid balance
      on the day of ICU discharge. Conclusions: Cytocam-IDF imaging to monitor
      microcirculation as a daily parameter is feasible and could become a valuable
      tool to non-invasively assess the tissue oxygenation at the bedside. An increase
      in TVD and PVD (functional capillary density) indicated the recruitment of the
      sublingual microcirculation in patients with diuretic therapy. Future research is
      needed to prove the correlation between the recruitment of the sublingual
      microcirculation and the de-escalation phase of the fluid management.

PMID- 30116526
TI  - A multi-center nested case-control study on hospitalization costs and length of
      stay due to healthcare-associated infection.
AB  - Background: In 2018, the Chinese government demanded nationwide implementation of
      medical insurance payment methods based on Single-Disease Payment (SDP), but
      during the operation process the medical insurance system did not fully consider
      the extra economic burden caused by healthcare-associated infection (HAI). HAIs
      can prolong the length of stay and increase the hospitalization costs, but only a
      few studies have been conducted in Sichuan province, China. We evaluated the
      hospitalization costs and length of stay due to HAI in Sichuan province based on
      the prevalence survey, and provided data reference for China's medical insurance
      reform. Methods: In the hospitals surveyed on the prevalence of HAI, a multi
      center nested case-control study was performed by a paired method. The study
      period was from 6 September 2016 to 30 November 2016. Binary outcomes were tested
      using chi2 test, continuous outcomes were tested using Wilcoxon matched-pairs
      signed rank test, intra-group comparisons were tested using multiple linear
      regression analysis. Results: A total of 225 pairs/450 patients were selected in
      51 hospitals, and 170 pairs/350 patients were successfully matched. The case
      fatality rate was 5.14% for the HAIs patients and 3.43% for non-HAs patients,
      there was no significant difference (chi2 = 0.627, P = 0.429); the median length
      of stay in patients with HAIs was 21 days, longer than that of patients with non
      HAI 16 days, the median of the difference between matched-pairs was 5 days, the
      difference was statistically significant (Z = 4.896, P = 0.000). The median
      hospitalization costs of patients with HAI were ?1732.83, higher than that of
      patients with non-HAI ?1095.29, the median of the difference between matched
      pairs were ?431.34, the difference was statistically significant (Z = 6.413, P =
      0.000). Multiple linear regression results showed that HAIs at different sites
      have caused different economic burdens, but in different economic regions, the
      difference was not statistically significant. Conclusions: In Sichuan, the
      hospitalization costs and length of stay caused by HAI should be given special
      attention in the current medical insurance reform. The proportion and scope of
      medical payment for patients with HAI at different sites should be different.
      Efforts need to be taken to incentivize reduction of HAI rates which will reduce
      hospitalization costs and length of stay.

PMID- 30116525
TI  - Enumerating the economic cost of antimicrobial resistance per antibiotic consumed
      to inform the evaluation of interventions affecting their use.
AB  - Background: Antimicrobial resistance (AMR) poses a colossal threat to global
      health and incurs high economic costs to society. Economic evaluations of
      antimicrobials and interventions such as diagnostics and vaccines that affect
      their consumption rarely include the costs of AMR, resulting in sub-optimal
      policy recommendations. We estimate the economic cost of AMR per antibiotic
      consumed, stratified by drug class and national income level. Methods: The model
      is comprised of three components: correlation coefficients between human
      antibiotic consumption and subsequent resistance; the economic costs of AMR for
      five key pathogens; and consumption data for antibiotic classes driving
      resistance in these organisms. These were used to calculate the economic cost of
      AMR per antibiotic consumed for different drug classes, using data from Thailand
      and the United States (US) to represent low/middle and high-income countries.
      Results: The correlation coefficients between consumption of antibiotics that
      drive resistance in S. aureus, E. coli, K. pneumoniae, A. baumanii, and P.
      aeruginosa and resistance rates were 0.37, 0.27, 0.35, 0.45, and 0.52,
      respectively. The total economic cost of AMR due to resistance in these five
      pathogens was $0.5 billion and $2.9 billion in Thailand and the US, respectively.
      The cost of AMR associated with the consumption of one standard unit (SU) of
      antibiotics ranged from $0.1 for macrolides to $0.7 for quinolones,
      cephalosporins and broad-spectrum penicillins in the Thai context. In the US
      context, the cost of AMR per SU of antibiotic consumed ranged from $0.1 for
      carbapenems to $0.6 for quinolones, cephalosporins and broad spectrum
      penicillins. Conclusion: The economic costs of AMR per antibiotic consumed were
      considerable, often exceeding their purchase cost. Differences between Thailand
      and the US were apparent, corresponding with variation in the overall burden of
      AMR and relative prevalence of different pathogens. Notwithstanding their
      limitations, use of these estimates in economic evaluations can make better
      informed policy recommendations regarding interventions that affect antimicrobial
      consumption and those aimed specifically at reducing the burden of AMR.

PMID- 30116527
TI  - IgG4 disease of the ear: Report and review.
AB  - In recent years, an immune-mediated disorder involving IgG4 has been described,
      which targets multiple organs and explains a number of disorders previously
      regarded as "idiopathic" or of unknown origin. Furthermore, the discovery of IgG4
      related disease (IgG4-RD) has placed a number of pathologies within its spectrum,
      linking symptoms and conditions formerly considered isolated. Reports of the
      manifestations of IgG4-RD in the head and neck are scarce. Otological
      manifestations have been reported, but only a handful of cases are available in
      the literature. This is the first report of recalcitrant serous otitis media
      secondary to IgG4-RD, confirmed by immunohistopathology. A case of IgG4-RD of the
      middle ear is presented, manifesting itself as recalcitrant serous otitis media.
      The case is presented from an otolaryngological and histopathological perspective
      and briefly reviews this rare disorder. The importance of the awareness of IgG4
      RD resides mainly in the fact that it is a treatable condition. This can
      potentially improve the quality of life of a number of patients, some of whom may
      not have had a clear diagnosis. A favorable response to glucocorticoids has been
      reported. In cases of persistent symptoms, immunosuppressive therapy has been
      used with success.

PMID- 30116528
TI  - Atezolizumab-related encephalitis in the intensive care unit: Case report and
      review of the literature.
AB  - Atezolizumab is a monoclonal antibody that targets programmed death ligand-1.
      Treatments with this drug may cause immune-related adverse events by creating an
      exaggerated inflammatory response. The most common side effects are fatigue,
      rash, and gastrointestinal symptoms. Cases of central nervous system toxicity
      such as encephalitis and encephalopathy are uncommon. We present the case of a 53
      year-old female with metastatic squamous cell carcinoma of the cervix who
      presented to the emergency room 13 days after receiving atezolizumab with altered
      mental status, headache, and meningeal signs. She was admitted to the intensive
      care unit. Infectious, anatomical, and neoplastic etiologies were ruled out. Auto
      immune meningoencephalitis was diagnosed and treated with high-dose steroids.
      Within 10 days of the diagnosis, she had clinical, radiological, and laboratory
      improvement. Given the increasing use of novel immunotherapies and life
      threatening side effects associated with them, healthcare providers in the
      intensive care unit should be aware of their diagnosis and management.

PMID- 30116529
TI  - Improvements in long standing cardiac pathologies by individualized homeopathic
      remedies: A case series.
AB  - We present three cases of cardiac arrest at different stages of pathology. Acute
      myocardial infarction and resulting heart failure is emerging as the leading
      cause of mortality. In the long run, acute episodes and cardiac remodelling can
      cause considerable damage and result in heart failure. In these cases,
      individualized homeopathic therapy was instituted along with the conventional
      medicines and the results were encouraging. The changes in the laboratory
      diagnostic parameters (single-photon emission computed tomography,
      electrocardiograph, echocardiography and ejection fraction as the case may be)
      are demonstrated over time. The key result seen in all three cases was the
      preservation of general well-being while the haemodynamic states also improved.
      While the three cases provide evidence of positive outcomes for homeopathic
      therapy, more extensive studies are required in a hospital setting to establish
      the real extent to which this therapy may be employed.

PMID- 30116530
TI  - Ileoileal intussusception in unspecific recurrent abdominal pain in adult: A case
      report.
AB  - Primary small bowel tumours are very uncommon accounting about 1% of all
      gastrointestinal tumours. Intestinal lipomas are a rare entity of benign tumours
      with an incidence at autopsy ranging from 0.04% to 4.5%, most being asymptomatic.
      Complications such as obstruction, haemorrhage, intussusception and perforation
      might demand invasive management. Among these, intussusception is the most rare
      complication of intestinal lipomas. Here, we present a case of intussusception in
      a 52-year-old female with a large intramural lipoma of the ileum.

PMID- 30116531
TI  - Combination statin and chemotherapy inhibits proliferation and cytotoxicity of an
      aggressive natural killer cell leukemia.
AB  - Background: Aggressive natural killer cell leukemia is a devastating disease,
      with an average patient survival time of less than 2 months following diagnosis.
      Due to P-glycoprotein-mediated resistance of the tumor cells most forms of
      chemotherapy are of limited efficacy, therefore new treatment strategies are
      needed. Statin drugs have recently been found to inhibit the growth of various
      tumor cell types. Methods: We investigated the effects of statin drug-mediated
      mevalonate pathway inhibition on cell proliferation, tumor-induced cytotoxicity,
      cell cycle progression and ERK MAP kinase signal transduction pathway activation.
      Flow cytometry was used to perform the cytotoxicity and cell cycle analyses and
      Western blotting was used to investigate ERK MAP kinase activation. Statistical
      significance was assessed by Student's t-test. Results: Fluvastatin and
      atorvastatin were found to inhibit cell growth and tumor-induced cytotoxicity.
      These effects were reversed by the addition of mevalonate, signifying that the
      impact of the drugs were on the mevalonate pathway. Both drugs affected cell
      cycle progression by causing a significant increase in the percentage of cells in
      the G0/G1 phase and a reduction in the S phase and the G2/M phases of the cell
      cycle. Low concentrations of statin drugs were able to abrogate ERK MAP kinase
      pathway activation, which is typically constitutively activated in aggressive
      natural killer cell leukemias and important in tumor-mediated cytotoxicity.
      Addition of statins to chemotherapy caused enhanced inhibition of cell growth and
      cytotoxicity, compared to either agent alone; a combination therapy that could
      conceivably benefit some patients. Conclusions: These investigations suggest that
      inhibiting the mevalonate pathway might provide a more effective therapy against
      this deadly disease when combined with chemotherapy. Given that millions of
      people are currently taking statin drugs to lower cholesterol levels, the risk
      profile for statin drugs and their side effects are well-known. Our studies
      suggest that it may be beneficial to explore statin-chemotherapy combination in
      the treatment of aggressive natural killer cell leukemias.

PMID- 30116532
TI  - The prognostic performance of qSOFA for community-acquired pneumonia.
AB  - Background: Quick Sepsis-related Organ Failure Assessment (qSOFA) is a new
      screening system for sepsis. The prognostic performance of qSOFA for patients
      with suspected infections outside the intensive care unit (ICU) is similar to
      that of full SOFA; however, its performance for community-acquired pneumonia
      (CAP) has not yet been evaluated in detail.The objectives of the present study
      were to compare the prognostic performance of qSOFA with existing pneumonia
      severity scores, such as CURB-65 (confusion, blood urea nitrogen > 19 mg/dL,
      respiratory rate >= 30/min, systolic blood pressure < 90 mmHg, or diastolic blood
      pressure <= 60 mmHg, age >= 65 years) and the pneumonia severity index (PSI), and
      examine its usefulness for predicting mortality and ICU admission in patients
      with CAP of high severity and mortality that requires hospitalization. Methods:
      We performed a secondary analysis of data from a prospective observational study
      of adult patients who were admitted to our hospital between October 2010 and June
      2016. We compared the prognostic performance of qSOFA, CURB-65, and PSI for
      predicting in-hospital mortality and ICU admission using the C statistics.
      Results: The median age of the 1045 enrolled patients was 77 (68-83) years, and
      71.4% were males. The in-hospital mortality and ICU admission rates of the entire
      cohort were 6.1 and 7.9%, respectively. All scores were significantly higher in
      non-survivors and ICU admission patients than in survivors and non-ICU admission
      patients (p < 0.001). The C statistics of qSOFA for predicting in-hospital
      mortality was 0.69 (95% CI 0.63-0.75), and no significant differences were
      observed between CURB-65 (C statistics, 0.75; 95% CI 0.69-0.81) and PSI (C
      statistics, 0.74; 95% CI 0.69-0.80). The C statistics of qSOFA for predicting ICU
      admission was 0.76 (95% CI 0.71-0.80), and no significant differences were noted
      between CURB-65 (C statistics, 0.73; 95% CI 0.67-0.79) and PSI (C statistics,
      0.72; 95% CI 0.66-0.78). Conclusions: Regarding hospitalized CAP, the prognostic
      performance of qSOFA for in-hospital mortality and ICU admission was not
      significantly different from those of CURB-65 and PSI. qSOFA only requires a few
      items and vital signs, and, thus, may be particularly useful for emergency
      department or non-respiratory specialists.

PMID- 30116533
TI  - Studying the effect of abdominal massage on the gastric residual volume in
      patients hospitalized in intensive care units.
AB  - Background: The main problem of hospitalized patients in intensive care units is
      feeding, and if the patient does not receive the daily caloric intake required to
      his body, he will have malnutrition and problems related to it. Abdominal massage
      is a method used to improve digestive function in various studies, but few
      studies have been conducted in intensive care units, and sometimes, contradictory
      results have been obtained. Therefore, the present study is conducted with the
      aim of determining the effect of abdominal massage on the gastric residual volume
      in patients hospitalized in intensive care units. Methods: This study was
      conducted as a clinical trial in Ahwaz, in 2017. Samples were 60 patients
      hospitalized in intensive care units who were randomly divided into case and
      control groups. The intervention period for the case group was 3 days and twice
      daily for 20 min. Measuring the gastric residual volume was investigated before
      the intervention and 1 hour after the second massage each day. Data were entered
      into the checklist designed by the researcher and were analyzed using SPSS
      version 24 and descriptive and inferential tests. Results: The gastric residual
      volume on the second and third day after the intervention was less than before
      the intervention (p value< 0.05), the gastric residual volume before intervention
      with after intervention in the control group during different days, on each of
      the 3 days after the intervention, was more than before the intervention (p
      value< 0.05), and the gastric residual volume after the intervention in different
      days and the mean of different days in the case group was lower than the control
      group (p value> 0.05). Conclusion: Results represent the effect of abdominal
      massage on reducing the gastric residual volume in patients hospitalized in
      intensive care units. Therefore, it is suggested that this method can be
      considered as a caring method in the daily care program for these patients. Trial
      registration: IRCT2017062134641N2, registered 26 July 2017.

PMID- 30116535
TI  - To intubate or not: ventilation is the question. A manikin-based observational
      study.
AB  - Introduction: There is a continuous debate concerning the superiority of
      endotracheal intubation on bag-valve-mask (BVM) ventilation in patients with
      cardiac arrest. In this manikin-based observational study, we evaluate and
      compare the performance of manual ventilation through a facemask (BVM) and an
      endotracheal tube (ETT). Methods: One hundred and forty healthcare providers were
      instructed to manually ventilate a manikin as they would do for a 75 kg adult
      patient in respiratory arrest. Each one was ventilating both through a facemask
      and an ETT for a 5 min period in a random order. Ventilatory parameters were
      measured by the ASL 5000 lung simulator and ventilation performance was analysed
      using a sliding window method published in a previous study to assess accurately
      ventilation efficiency. Results: The mean ventilation rate was high whatever the
      technique used (24 bpm). A weak relationship between manual ventilation
      performance and the type of interface used was observed (p=0.0484). The overall
      rate of adequate ventilation was low even if we noticed a slight improvement when
      ventilating through an ETT (13.21% vs 7.5% of adequate ventilation). However, the
      rate of hyperventilation did not differ between mask and tube (79% vs 77%). A
      significant relationship is observed between professional category, the size of
      the hand squeezing the bag and manual ventilation performance (p<0.05).
      Conclusion: Whatever the interface used, healthcare professionals are still
      struggling to perform manual ventilation efficiently according to international
      guidelines. Ventilation with an ETT does not prove to be significantly more
      efficient than with a facemask. It would be therefore important to recentre the
      debate on controlling ventilatory parameters with current devices. Focusing on
      training may maximise manual ventilation efficiency and minimise the loss of time
      during cardiopulmonary resuscitation.

PMID- 30116534
TI  - Rare and unusual case of anti-factor XI antibodies in patient with plasma cell
      leukemia.
AB  - Background: The acquired inhibitors of coagulation have been observed in very
      rare cases of monoclonal gammopathies. We report a very rare case of anti-factor
      XI antibodies in patient with plasma cell leukemia (PCL). Case presentation: This
      is a 59-year-old male patient without pathological history, admitted to the
      nephrology department for management of renal insufficiency and anemia syndrome.
      The history and physical examination revealed stigmata of hemorrhagic syndrome
      including hemothorax and hemoptysis. The hemostasis assessment showed an isolated
      prolonged activated partial thromboplastin time (APTT) with APTT ratio = 2.0.The
      index of circulating anticoagulant (37.2%) revealed the presence of circulating
      anticoagulants. The normalized dilute Russell viper venom time ratio of 0.99 has
      highlighted the absence of lupus anticoagulants. The coagulation factors assay
      objectified the decrease of the factor XI activity corrected by the addition of
      the control plasma confirming the presence of anti-factor XI autoantibodies. In
      addition, the blood count showed bicytopenia with non-regenerative normocytic
      normochromic anemia and thrombocytopenia. The blood smear demonstrated a plasma
      cell count of 49% (2842/mm3) evoking PCL. The bone marrow was invaded up to 90%
      by dystrophic plasma cells. The biochemical assessment suggested downstream renal
      and electrolyte disturbances from exuberant light chain production with
      abnormalities including hyperuricemia, hypercalcemia, elevated lactate
      dehydrogenase, non nephrotic-range proteinuria and high level of C reactive
      protein. The serum protein electrophoresis showed the presence of a monoclonal
      peak. The serum immunofixation test detects the presence of monoclonal free
      lambda light chains. He was treated with velcade, thalidomide and dexamethasone.
      The patient died after 2 weeks despite treatment. Conclusion: Both PCL and anti
      factor XI inhibitors are two very rare entities. To the best of our knowledge,
      this is the first reported case of a factor XI inhibitor arising in the setting
      of PCL. Factor inhibitors should be suspected in patients whose monoclonal
      gammopathies are accompanied by bleeding manifestations.

PMID- 30116536
TI  - Reducing hospital admissions for COPD: perspectives following the Christchurch
      Earthquake.
AB  - The devastating 2011 earthquake in Christchurch destroyed or badly damaged
      healthcare infrastructure, including Christchurch Hospital. This forced change in
      management of exacerbations of chronic obstructive pulmonary disease (COPD),
      which until that point had frequently led to admission to hospital and focused
      attention on providing safe community options for care. This paper describes the
      process of understanding factors contributing to high admission frequency with
      exacerbations of COPD and also describes a process of change, predominantly to
      healthcare delivery systems and philosophies, and the subsequent outcomes. What
      became clear in understanding admissions with COPD to Christchurch Hospital was
      that the behaviour of the patient, in the context of exacerbations, and the
      subsequent response of the system to the patient, led to admission being the
      default option, in spite of low severity of the exacerbation itself. By altering
      systems' responses to exacerbations, with a linked care process between
      ambulances, community care and hospitals, we were able to safely reduce
      admissions for COPD, with a sustained overall reduction in bed-day occupancy for
      COPD of ~48%. We would encourage these discussions and changes to occur without
      the stimulus of an earthquake in your healthcare environment!

PMID- 30116537
TI  - Providing safe and effective pleural medicine services in the UK: an aspirational
      statement from UK pleural physicians.
AB  - Physicians face considerable challenges in ensuring safe and effective care for
      patients admitted to hospital with pleural disease. While subspecialty
      development has driven up standards of care, this has been tempered by the
      resulting loss of procedural experience in general medical teams tasked with
      managing acute pleural disease. This review aims to define a framework though
      which a minimum standard of care might be implemented. This review has been
      written by pleural clinicians from across the UK representing all types of
      secondary care hospital. Its content has been formed on the basis of literature
      review, national guidelines, National Health Service England policy and consensus
      opinion following a round table discussion. Recommendations have been provided in
      the broad themes of procedural training, out-of-hours management and pleural
      service specification. Procedural competences have been defined into descriptive
      categories: emergency, basic, intermediate and advanced. Provision of emergency
      level operators at all times in all trusts is the cornerstone of out-of-hours
      recommendations, alongside readily available escalation pathways. A proposal for
      minimum standards to ensure the safe delivery of pleural medicine have been
      described with the aim of driving local conversations and providing a framework
      for service development, review and risk assessment.

PMID- 30116538
TI  - Step oximetry test: a validation study.
AB  - Introduction: Step climbing is a potentially useful modality for testing exercise
      capacity. However, there are significant variations between test protocols and
      lack of consistent validation against gold standard cycle ergometry
      cardiopulmonary exercise testing (CPET). The purpose of the study was to validate
      a novel technique of exercise testing using a dedicated device. Methods: We built
      a step oximetry device from an adapted aerobics step and pulse oximeter connected
      to a computer. Subjects performed lung function tests, a standard incremental
      cycle CPET and also a CPET while stepping on and off the step oximetry device to
      maximal exertion. Data from the step oximetry device were processed and
      correlated with standard measurements of pulmonary function and cycle CPET.
      Results: We recruited 89 subjects (57 years, 50 men). Oxygen uptake (VO2) was 0.9
      mL/kg/min (95% CI -3.6 to 5.4) higher in the step test compared with the gold
      standard cycle CPET, p<0.001. VO2 in the two techniques was highly correlated
      (R=0.87, p<0.001). Work rate during stair climbing showed the best correlation
      with VO2 (R=0.69, p<0.0001). Desaturation during step climbing correlated
      negatively with diffusion capacity for carbon monoxide (r=-0.43, p<0.005). No
      adverse events occurred. Conclusions: The step oximetry test was a maximal test
      of exertion in the subjects studied, achieving slightly higher VO2 than during
      the standard test. The test was safe to perform and well tolerated by the
      patients. Parameters derived from the step oximetry device correlated well with
      gold standard measurements. The step oximetry test could become a useful and
      standardisable exercise test for clinical settings where advanced testing is not
      available or appropriate.

PMID- 30116539
TI  - Dose modification and dose intensity during treatment with pirfenidone: analysis
      of pooled data from three multinational phase III trials.
AB  - Introduction: Temporary dose modifications, such as reductions or interruptions,
      may allow patients to better manage adverse events (AEs) associated with
      pirfenidone use and continue treatment for idiopathic pulmonary fibrosis (IPF).
      However, the impact of such dosing adjustments on efficacy and safety is
      uncertain. Methods: Patients randomised to receive treatment with pirfenidone
      2403 mg/day or placebo in the Clinical Studies Assessing Pirfenidone in
      Idiopathic Pulmonary Fibrosis: Research of Efficacy and Safety Outcomes (CAPACITY
      (Study 004 (NCT00287716)) and Study 006 (NCT00287729))) and Assessment of
      Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis
      (ASCEND (Study 016 (NCT01366209)) trials were included in the analysis (n=1247).
      Descriptive statistics and a linear mixed-effects model (slope analysis) for
      annual rate of decline in forced vital capacity (FVC) by dose intensity were
      performed. Treatment-emergent AEs (TEAEs) were summarised and grouped by dose
      intensity or body size. Results: Dose reductions and interruptions occurred in
      76.9% (95% CI 73.4% to 80.1%) and 46.5% (95% CI 42.6% to 50.6%) of patients
      receiving pirfenidone vs 72.0% (95% CI 68.3% to 75.4%) and 31.1% (95% CI 27.5% to
      34.9%) of patients receiving placebo, respectively. Dose interruptions tended to
      occur during the first 6 months of treatment, whereas dose reductions exhibited
      more variability. Less FVC decline from baseline was observed in patients
      receiving pirfenidone versus placebo at >90% dose intensity (p<0.001) or <=90%
      dose intensity (p=0.0191), showing treatment benefit in both subgroups of dose
      intensity. No meaningful relationship between weight and TEAEs was observed.
      Conclusion: Dose interruptions, which may be required to manage TEAEs, mostly
      occurred during the first 6 months of treatment. Despite dose reductions and
      interruptions, most patients with IPF maintained relatively high dose intensity
      on pirfenidone, without compromising its treatment effect compared with placebo.
      Trial registration numbers: NCT00287729, NCT00287716, NCT01366209.

PMID- 30116540
TI  - Cardiac structure and function with and without metabolic syndrome: the
      Echocardiographic Study of Latinos (Echo-SOL).
AB  - Objective: We assessed the hypothesis that metabolic syndrome is associated with
      adverse changes in cardiac structure and function in participants of the
      Echocardiographic Study of Latinos (Echo-SOL). Methods: Non-diabetic Echo-SOL
      participants were included in this cross-sectional analysis. Metabolic syndrome
      was defined according to the American Heart Association/National Heart, Lung, and
      Blood Institute 2009 Joint Scientific Statement. Survey multivariable linear
      regression analyses using sampling weights were used adjusting for multiple
      potential confounding variables. Additional analysis was stratified according to
      the presence/absence of obesity (body mass index (BMI) >=25 kg/m2) and the
      presence/absence of metabolic syndrome. Results: Within Echo-SOL, 1260
      individuals met inclusion criteria (59% female; mean age 55.2 years). Compared
      with individuals without metabolic syndrome, those with metabolic syndrome had
      lower medial and lateral E' velocities (-0.4 cm/s, (SE 0.1), p=0.0002; -0.5 cm/s
      (0.2), p=0.02, respectively), greater E/E' (0.5(0.2), p=0.01) and worse two
      chamber left ventricular longitudinal strain (0.9%(0.3), p=0.009), after
      adjusting for potential confounding variables. Increased left ventricular mass
      index (9.8 g/m2 (1.9), p<0.0001 and 7.5 g/m2 (1.7), p<0.0001), left ventricular
      end-diastolic volume (11.1 mL (3.0), p=0.0003 and 13.3 mL (2.7), p<0.0001), left
      ventricular end-systolic volume (5.0 mL (1.4), p=0.0004 and 5.7 mL (1.3)
      p<0.0001) and left ventricular stroke volume (10.2 mL (1.8), p<0.0001 and 13.0 mL
      (2.0), p<0.0001) were observed in obese individuals with and without metabolic
      syndrome compared with individuals with normal weight without metabolic syndrome.
      In sensitivity analyses, individuals with normal weight (BMI <25 kg/m2) and
      metabolic syndrome had worse left ventricular global longitudinal strain
      (2.1%(0.7), p=0.002) and reduced left ventricular ejection fraction (-3.5%(1.4),
      p=0.007) compared with normal-weight individuals without metabolic syndrome.
      Conclusions: In a sample of US Hispanics/Latinos metabolic syndrome was
      associated with worse left ventricular systolic and diastolic function. Adverse
      changes in left ventricular size and function were observed in obese individuals
      with and without metabolic syndrome but decreased left ventricular function was
      also present in normal-weight individuals with metabolic syndrome.

PMID- 30116542
TI  - Revisiting the evolution of tuberculosis therapy: historical reflections in the
      modern era.
AB  - Management of tuberculosis (TB) has witnessed several changes over the past
      decades. While medical management is now the mainstay of therapy, surgical
      intervention was once the only treatment option physicians had to offer. We
      discuss some historical surgical procedures and take a quick glance at the
      evolution of TB therapy. We note the importance of adequate history-taking and
      the implications of what seemingly obsolete techniques may have in contemporary
      practice. We also highlight the re-emergence of surgical options in the modern
      era with the rise of multidrug-resistance.

PMID- 30116541
TI  - Development of a model to predict 5-year risk of severe hypoglycemia in patients
      with type 2 diabetes.
AB  - Objective: We constructed a predictive model of long-term risk for severe
      hypoglycemia (SH: hypoglycemia requiring assistance) in patients with type 2
      diabetes (T2DM). Research design and methods: Data from the Action to Control
      Cardiovascular Risk in Diabetes (ACCORD) study (original n=10 251, n=5135 used in
      the current analysis), a randomized, multicenter, double 2*2 factorial design
      study examining the effect of glycemic, blood pressure, and lipid control on
      cardiovascular outcomes in patients with diagnosed T2DM, were used. Over the
      follow-up (3.76+/-1.12 years), the ACCORD participants experienced 607 incident
      SH events. Cox regression was used to identify the SH risk prediction model.
      Results: We identified 17 predictors-glycemic management, age, race, education,
      waist circumference, medications (insulin, antihypertensive, HMG-CoA reductase
      inhibitors, sulfonylurea, biguanide and meglitinide), years since diabetes
      diagnosis, history of hypoglycemia in the last week, systolic blood pressure,
      diastolic blood pressure, serum creatinine, and urinary albumin creatinine ratio
      to construct a prediction model for SH (c-statistic=0.782). Using this
      information, we derived point scores to estimate the 5-year risk for SH in
      individual patients with T2DM. After adjusting for other variables in the model,
      the three strongest predictors for SH over 5 years were intensive glycemic
      management (HR=2.37, 95% CI 1.99 to 2.83), insulin use (HR=2.14, 95% CI 1.77 to
      2.59), and antihypertensive medication use (HR=1.90, 95% CI 1.26 to 2.86).
      Conclusion: Using the ACCORD data, we identified attributes to predict 5-year
      risk of SH in patients with T2DM, which warrant evaluation in broader populations
      to determine applicability.

PMID- 30116544
TI  - Association Between Low-Molecular-Weight Heparin and Risk of Bleeding Among
      Hemodialysis Patients: A Retrospective Cohort Study.
AB  - Background: Low-molecular-weight heparins (LMWH) replaced unfractionated heparin
      (UFH) in multiple indications. Although LMWH efficacy in hemodialysis was
      demonstrated through multiple studies, their safety remains controversial. The
      potential bioaccumulation in patients undergoing chronic hemodialysis raised the
      question of bleeding risk among this population. Objective: The aim of this study
      was to evaluate bleeding risk among patients with chronic hemodialysis receiving
      LMWH or UFH for the extracorporeal circuit anticoagulation. Design: We conducted
      a retrospective cohort study on data extracted from the Regie de l'assurance
      maladie du Quebec (RAMQ) and Med-Echo databases from January 2007 to March 2013.
      Setting: Twenty-one hemodialysis centers in the province of Quebec, Canada.
      Patients: Chronic hemodialysis patients. Measurements: Bleeding risk evaluated by
      proportional Cox model for time-dependent exposure using demographics,
      comorbidities, and drug use as covariates. Methods: Minor, major, and total
      bleeding events identified using International Classification of Diseases, Ninth
      Revision (ICD-9)/International Classification of Diseases, Tenth Revision (ICD
      10) codes in the RAMQ and Med-Echo databases. Exposure status to LMWH or UFH was
      collected through surveys at the facility level. Results: We identified 5322
      prevalent and incident patients with chronic hemodialysis. The incidence rate for
      minor, major, and total bleeding was 9.45 events/1000 patient-year (95%
      confidence interval [CI]: 7.61-11.03), 24.18 events/1000 patient-year (95% CI:
      21.52-27.08), and 32.88 events/1000 patient-year (95% CI: 29.75-36.26),
      respectively. We found similar risks of minor adjusted hazard ratio (HR: 1.04;
      95% CI: 0.68-1.61), major (HR: 0.83; 95% CI: 0.63-1.10), and total bleeding (HR:
      0.90; 95% CI: 0.72-1.14) when comparing LMWH with UFH. Limitations: Potential
      misclassification of patients' exposure status and possible underestimation of
      minor bleeding risk. Conclusion: LMWH was not associated with a higher minor,
      major, or total bleeding risk. LMWH did not increase the risk of bleeding
      compared with UFH for the extracorporeal circuit anticoagulation in hemodialysis.
      The convenience of use and predictable effect made LMWH a suitable alternative to
      UFH in hemodialysis.

PMID- 30116543
TI  - Effect of Rosuvastatin on Acute Kidney Injury in Sepsis-Associated Acute
      Respiratory Distress Syndrome.
AB  - Background: Acute kidney injury (AKI) commonly occurs in patients with sepsis and
      acute respiratory distress syndrome (ARDS). Objective: To investigate whether
      statin treatment is protective against AKI in sepsis-associated ARDS. Design:
      Secondary analysis of data from Statins for Acutely Injured Lungs in Sepsis
      (SAILS), a randomized controlled trial that tested the impact of rosuvastatin
      therapy on mortality in patients with sepsis-associated ARDS. Setting: 44
      hospitals in the National Heart, Lung, and Blood Institute ARDS Clinical Trials
      Network. Patients: 644 of 745 participants in SAILS who had available baseline
      serum creatinine data and who were not on chronic dialysis. Measurements: Our
      primary outcome was AKI defined using the Kidney Disease Improving Global
      Outcomes creatinine criteria. Randomization to rosuvastatin vs placebo was the
      primary predictor. Additional covariates include demographics, ARDS etiology, and
      severity of illness. Methods: We used multivariable logistic regression to
      analyze AKI outcomes in 511 individuals without AKI at randomization, and 93 with
      stage 1 AKI at randomization. Results: Among individuals without AKI at
      randomization, rosuvastatin treatment did not change the risk of AKI (adjusted
      odds ratio: 0.99, 95% confidence interval [CI]: 0.67-1.44). Among those with
      preexisting stage 1 AKI, rosuvastatin treatment was associated with an increased
      risk of worsening AKI (adjusted odds ratio: 3.06, 95% CI: 1.14-8.22). When serum
      creatinine was adjusted for cumulative fluid balance among those with preexisting
      stage 1 AKI, rosuvastatin was no longer associated worsening AKI (adjusted odds
      ratio: 1.85, 95% CI: 0.70-4.84). Limitations: Sample size, lack of urine output
      data, and prehospitalization baseline creatinine. Conclusion: Treatment with
      rosuvastatin in patients with sepsis-associated ARDS did not protect against de
      novo AKI or worsening of preexisting AKI.

PMID- 30116545
TI  - Antibiotic Dosing in Sustained Low-Efficiency Dialysis in Critically Ill
      Patients.
AB  - Purpose of review: Sustained low-efficiency dialysis (SLED) is increasingly used
      as a renal replacement modality in critically ill patients with acute kidney
      injury (AKI) and hemodynamic instability. There is, therefore, a greater need for
      the understanding of the antibiotic dosage and pharmacokinetics in these
      patients, to provide them with optimal therapy. Sources of information:
      PubMed/Medline, Embase, and Google Scholar. Methods: PubMed/Medline, Embase, and
      Google Scholar databases were searched using a combination of key words:
      dialysis, end stage renal disease, renal failure, sustained low efficiency
      dialysis, extended daily dialysis, prolonged intermittent renal replacement
      therapy (PIRRT), and antibiotic dosing. Studies that investigated antibiotic
      dosing and pharmacokinetics during SLED/extended daily dialysis/PIRRT were
      selected for this review. Key findings: Eleven studies met inclusion criteria and
      selected for data extraction. The data with regard to dialysis specifications,
      type of antibiotic including dosages, drug clearances, and dosage recommendations
      are summarized in Table 1. It is a challenge to find therapeutic doses for
      antibiotics during SLED therapy because, in general, only aminoglycosides and
      vancomycin can be assayed in clinical laboratories. Limitations: Although current
      studies on antibiotic dosing in SLED are limited due to diverse and undersized
      patient populations, antibiotic dosage adjustments for patients receiving SLED
      discussed here will serve as a valuable guide. Future large-scale research should
      focus on establishing guidelines for antibiotic dosage in SLED. Implications:
      Pharmacokinetic principles should be taken into consideration for the appropriate
      dosing of drugs during SLED, yet it is vital to monitor response to drug to make
      sure therapeutic goals are achieved. Antibiotic dosing and timing relative to the
      initiation of SLED may be important to maximize either the time above the minimum
      inhibitory concentration (MIC) (time-dependent) or the peak to MIC ratio
      (concentration-dependent), balancing efficacy and toxicity concerns. Critical
      care physicians should liaise with nephrologists to make decisions regarding
      appropriate antibiotic dosing in patients undergoing SLED.

PMID- 30116546
TI  - Diagnostic accuracy of a pH stick, modified to detect gastric lipase, to confirm
      the correct placement of nasogastric tubes.
AB  - Objective: The correct placement of a nasogastric feeding tube is usually
      confirmed by establishing that an aspirate is acidic using a pH stick. However,
      antacid medication and achlorhydria can cause false negative pH tests that may
      delay feeding and increase resource use. The purpose of this study was to
      evaluate a modified pH stick designed to detect gastric lipase and therefore
      reduce false negative tests. Methods: In this prospective observational study, a
      convenience sample of adult patients who had either gastric and oesophageal
      samples taken during routine diagnostic gastroscopy (n=97) or bronchial and
      saliva samples taken during a bronchoscopy (n=106). The samples were tested by
      blinded observers using the modified and standard pH sticks. The sensitivities
      and specificities of the two pH sticks in identifying gastric and non-gastric
      aspirates were compared using the pH cut-off <=5.5. Results: The sensitivities of
      a pH<=5.5 to correctly identify gastric samples were 66% (95% CI 56 to 75) and
      68% (95% CI 57 to 77) for the modified and the standard pH, respectively. The
      specificities were 81% (95% CI 76 to 85) and 79% (95% CI 74 to 84). There were no
      significant differences in the distribution of the discordant results between the
      paired gastric and non-gastric samples for both the modified and standard pH
      sticks at pH<=5.5 (both McNemar's tests, p>=0.05). Conclusions: There were no
      significant differences between the paired modified and standard pH tests for the
      gastric samples. Due to the limited accuracy of pH sticks, further research is
      required to identify accurate and cost-effective bedside methods to confirm the
      correct placement of nasogastric tubes.

PMID- 30116547
TI  - The impact of endometrial thickness (EMT) on the day of human chorionic
      gonadotropin (hCG) administration on pregnancy outcomes: a 5-year retrospective
      cohort analysis in Malaysia.
AB  - Background: Chances of pregnancy in relation to endometrial thickness (EMT)
      remain elusive albeit some literatures suggest poorer pregnancy outcomes below
      the threshold of 6-7 mm, notwithstanding others perceive detrimental effect at
      thicker EMT. We aim to examine the implication of EMT on pregnancy outcomes using
      a cut-off of 8 mm and further explore for any effect of 'thick' EMT in our
      patient population. Methods: This was a retrospective cohort study performed for
      162 women to assess the associations between EMT on the human chorionic
      ganadotropin (hCG) trigger day and pregnancy outcomes in infertile patients
      undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI)
      and autologous fresh embryo transfer (ET) in controlled ovarian stimulation (COS)
      cycles under an assisted reproductive technology (ART) shared-care programme
      between public and private institutions from January 2012 through December
      2016.The associations between pregnancy outcomes [Total Pregnancy Rate (TPR),
      Biochemical Pregnancy Rate (BPR), Clinical Pregnancy Rate (CPR), Ongoing
      Pregnancy Rate (OPR)/ Live Birth Delivery Rate (LBDR), Miscarriage Rate (MR) and
      Implantation Rate (IR)] and EMT (< 8 or >= 8 mm) on the hCG trigger day were
      evaluated. Besides, the associations between pregnancies outcomes with EMT >= 14
      mm and >= 8 to < 14 mm were further assessed. Results: We found that the >=8 mm
      group had a higher TPR (55.4% vs 21.4%; p = 0.015) and CPR (52.0% vs 21.4%; p =
      0.029). However, the BPR, MR, OPR/ LBDR and IR were not associated with the EMT
      (p > 0.05). All pregnancy outcomes were comparable for >=14 mm and >= 8 to < 14
      mm subgroups. Conclusions: Our findings suggest that EMT < 8 mm on hCG trigger
      day could adversely affect TPR and CPR in infertile patients undergoing IVF/ICSI
      ET. Besides, we also disprove the notion of reduced chances of pregnancy with EMT
      >= 14 mm. The findings are based on completed cycles which each has demonstrated
      a triple-line endometrial pattern on the hCG trigger day with fresh autologous ET
      consisted of high-quality morphological gradings. However, our findings are still
      preliminary to suggest decision for ET transfer, cycle cancellation or adjunctive
      therapies. Further studies with larger sample size from this geographical region
      are required to verify the findings.

PMID- 30116548
TI  - Incidence of Plasmodium infections and determinant factors among febrile children
      in a district of Northwest Ethiopia; a cross-sectional study.
AB  - Background: According to the Ethiopian national malaria indicator survey of 2015,
      the highest burden of Plasmodia infection resided among the school-age children.
      Even though several studies revealed various determinant factors of childhood
      malaria, consistent findings are not reported across the nation and elsewhere.
      This in turn creates obstacles in implementing exactprevention and control
      measures in the study area in particular and the country at large. Objectives:
      The aim of this study is to determine the incidence of Plasmodium and determinant
      factors among febrile children in Northwest Ethiopia. Methods: This cross
      sectional study was conducted from April-August 2016. Blood samples were
      collected from febrile children selected by systematic random sampling. Thin and
      thick blood films were prepared and stained with Giemsa. Statistical analysis was
      done via SPSS version 20 statistical software and data were summarized with
      percentages and frequencies. The bi-variate and multi-variate logistic
      regressions were used to measure strength of association between Plasmodium
      infection and determinant factors, and to rule out confounders, respectively.
      Result: Among a total of 333 febrile children, 146 (43.8%) were positive for the
      Plasmodia. The prevalence of plasmodium infection was 47%, 50%, and 40%, among
      the age groups of 6-8, 9-10 and 11-14 years, respectively. Prevalence of
      plasmodium among male and female children was 44.2% and 43.5%, respectively.
      Shorter distance from stagnant water (AOR (adjusted odds ratio) =43, 95% CI
      (confidence interval):2.8-680.7; P < 0.01), family size (AOR =14.7, 95% CI:(1.4
      151.2; P = 0.02), outdoor sleeping (AOR =36.6, 95% CI:2.4-554.2; P < 0.01,
      irregular bed net use (AOR =21.1, 95% CI:2.9-154.7; P < 0.01), and late bed time
      (AOR =31.9, 95% CI:2.8-371.3; P < 0.01) showed statistically significant
      association with plasmodium infection. Conclusion: The incidence of Plasmodium
      infection is high among febrile children in the study area. Shorter distance from
      stagnant water, larger family size, outdoor sleeping, irregular bed net use, and
      late night sleeping are the major determinant factors for the high incidence of
      malaria. Therefore, community mobilization and health education should focus on
      the specific determinant factors of plasmodium infection to alleviate incidence
      of malaria among the school children.

PMID- 30116550
TI  - Reference videos reduce variability of motor dysfunction assessments in multiple
      sclerosis.
AB  - Motor dysfunction, particularly ataxia, is one of the predominant clinical
      manifestations in patients with multiple sclerosis (MS). Assessment of motor
      dysfunction suffers from a high variability. We investigated whether the clinical
      rating of ataxia can be improved through the use of reference videos, covering
      the spectrum of severity degrees as defined in the Neurostatus-Expanded
      Disability Status Scale. Twenty-five neurologists participated. The variability
      of their assessments was significantly lower when reference videos were used (SD
      = 0.12; range = 0.40 vs SD = 0.26; range = 0.88 without reference videos; p =
      0.013). Reference videos reduced the variability of clinical assessments and may
      be useful tools to improve the precision and consistency in the clinical
      assessment of motor functions in MS.

PMID- 30116549
TI  - Differences in clinical features between optic neuritis in neuromyelitis optica
      spectrum disorders and in multiple sclerosis.
AB  - Background: Optic neuritis (ON) is one of the common manifestations both in
      neuromyelitis-optica spectrum disorders (NMOSD) and in multiple sclerosis (MS).
      Objectives: The objective of this paper is to compare clinical presentations,
      laboratories and imaging findings in ON associated with MS and NMOSD. Methods: A
      retrospective chart review was performed in patients presenting with ON in 59
      NMOSD patients with 72 eyes' involvement and 163 ON attacks, and 20 MS patients
      with 23 eyes' involvement and 36 ON attacks. Results: ON-NMOSD patients had
      recurrent ON more often and tended to have simultaneous bilateral ON involvement
      at their first ON attack. Individuals with ON-NMOSD revealed worse visual acuity
      at first ON attacks and also had poorer long-term visual outcome than those with
      ON-MS, with nearly half of ON-NMOSD patients still having LogMAR visual acuity
      >=1 at their last follow-up (p = 0.035). Significant thinner average retinal
      nerve fiber layer thickness was found in the ON-NMOSD group. We found no
      significant differences in segmentation location of the optic nerve lesions and
      the length of involvement between the two groups. Conclusions: It was difficult
      to completely differentiate ON-NMOSD from ON-MS. ON-NMOSD patients, however,
      tended to have simultaneous bilateral ON involvement and poorer long-term visual
      outcome than individuals with ON-MS.

PMID- 30116551
TI  - Study protocol: a randomized, double-blind, parallel, two-arm, placebo control
      trial investigating the feasibility and safety of immunoglobulin treatment in
      COPD patients for prevention of frequent recurrent exacerbations.
AB  - Background: Chronic obstructive pulmonary disease (COPD) is a chronic progressive
      inflammatory disease of the airways, associated with frailty, disability, co
      morbidity, and mortality. Individuals with COPD experience increased risk and
      rates of acute exacerbation as their lung disease worsens. Current treatments to
      prevent acute exacerbation of COPD (AECOPD) are only modestly effective. New
      therapies are needed to improve the quality of life and clinical outcomes for
      individuals living with COPD and especially for those prone to frequent recurrent
      AECOPD. Recent research has suggested an association of gammaglobulin or
      immunoglobulin G levels with AECOPD and a favorable effect of an immunoglobulin
      treatment on the frequency of recurrent AECOPD, healthcare provider visits,
      treatments, and hospitalizations. However, control trials are required to confirm
      this apparent association and therapeutic effect. This study aims to assess if
      intravenous immunoglobulin (IVIG) therapy is feasible, safe, tolerable, and
      potentially effective in reducing the frequency of recurrent AECOPD.
      Methods/design: Adult COPD patients at The Ottawa Hospital (TOH) will be
      recruited to partake in a randomized double-blind, parallel, two-arm, placebo
      control trial. Eligible patients will be administered either IVIG or normal
      saline following 1:1 randomization and every 4 weeks for 1 year. The primary
      outcome of feasibility will be determined by recruitment, patient adherence,
      safety and tolerance, success of the follow-up procedures, and outcome
      measurement. The safety and tolerability will be assessed through adverse events,
      adherence, and study withdrawals. Efficacy trends will be investigated by
      assessing incidence rates of AECOPD, improvement in quality of life, and
      healthcare services use and cost. Discussion: The study results will inform
      larger studies designed to confirm a clinically significant therapeutic effect in
      identifiable populations which would be a major advance in the care of COPD
      patients. Trial registration number: ClinicalTrial.gov, NCT03018652 and
      NCT02690038.

PMID- 30116552
TI  - Factors affecting interspecific differences in genetic divergence among
      populations of Anolis lizards in Cuba.
AB  - Background: Geographical patterns and degrees of genetic divergence among
      populations differ between species, reflecting relative potentials for speciation
      or cladogenesis and differing capacities for environmental adaptation.
      Identification of factors that contribute to genetic divergence among populations
      is important to the understanding of why some species exhibit greater
      interpopulation genetic divergence. In this study, we calculated the mean
      pairwise genetic distances among populations as species' average genetic
      divergence by a phylogeny using nuclear and mitochondrial genes of 303
      individuals from 33 Cuban Anolis species and estimated species ages by another
      phylogeny using nuclear and mitochondrial genes of 51 Cuban and 47 non-Cuban
      Anolis species. We identified factors that influence species' differences in
      genetic divergence among 26 species of Anolis lizards from Cuba. Species ages,
      environmental heterogeneity within species ranges, and ecomorph types were
      considered as factors affecting average genetic divergences among populations.
      Results: The phylogenies presented in this study provide the most comprehensive
      sampling of Cuban Anolis species to date. The phylogeny showed more conservative
      evolution of Anolis ecomorphs within Cuba and identified twig anoles as a
      monophyletic group. Subsequent Phylogenetic Generalized Least Squares (PGLS)
      analyses showed that species age was positively correlated with species' average
      genetic divergence among populations. Conclusion: Although previous studies have
      focused on factors affecting genetic divergence within species, the present study
      showed for the first time that species differences in genetic divergence could be
      largely affected by species age.

PMID- 30116554
TI  - Modification of pectoral fins occurs during the larva-to-juvenile transition in
      the mudskipper (Periophthalmus modestus).
AB  - Background: Mudskippers are amphibious fishes that use their pectoral fins to
      move on land. Their pectoral fins are specifically modified for terrestrial
      locomotion. Studies of the anatomy and kinematics of adult mudskippers suggest
      that modifications of the pectoral fins, such as their protrusion and elongation
      of the proximal radials, may provide greater control and flexibility in pectoral
      fin-based locomotion. However, it is unknown when and how the unique features of
      these pectoral fins form during the development of mudskippers, which begin life
      as a planktonic organism. Results: Here we examined the developmental process of
      the pectoral fins of the mudskipper Periophthalmus modestus to address these
      questions. We also observed other developmental characteristics to provide
      clarified descriptions, including indicative morphological changes that occur
      during metamorphosis. Conclusion: Our results show that the localized cell
      division of the proximal part of the endoskeletal disc-the primordium of the
      proximal radials-and subsequent cell division along the proximal-distal axis,
      which is restricted to the distal part of the disc during the larva-to-juvenile
      transition (metamorphosis), lead to the elongation of the proximal radials.

PMID- 30116555
TI  - Prevalence and clinical correlates of rheumatoid factor and anticitrullinated
      protein antibodies in patients with idiopathic inflammatory myopathy.
AB  - Objective: As rheumatoid factor (RF) and anticitrullinated protein antibodies
      (ACPAs) are not routinely tested in idiopathic inflammatory myositis (IIM),
      little is known about their prevalence and clinical implications in this patient
      group. In antisynthetase syndrome (ASS), presence of ACPA is reportedly
      associated with more severe and erosive arthritis. We aim to retrospectively
      determine the prevalence of RF and ACPA in a cross-sectional cohort of 121
      patients diagnosed with IIM and to assess clinical associations. Methods: Serum
      samples from 121 patients diagnosed with polymyositis (n=30), dermatomyositis
      (n=41), ASS (n=37), inclusion body myositis (n=1), necrotising autoimmune
      myopathy (n=5) or overlap myositis (n=7) were analysed. RF was evaluated by
      nephelometry (Immage 800, Beckman-Coulter); anti-CCP antibodies were identified
      using fluoro enzyme immunoassays (Immuno-Cap 250, Thermo Fisher). Values above 40
      IU/mL and 7 U/mL were considered positive for RF and ACPA, respectively. Results:
      The prevalence of RF and ACPA was 9.09% and 4.96%, respectively. No significant
      differences were observed between RF/ACPA positive versus negative patients.
      There was a numerical trend for RF-positive IIM patients to be older and have
      lower forced expiratory volume in 1 s levels. Conclusions: RF and ACPA are
      prevalent in IIM, although we detected a lower prevalence than reported in
      previous studies. Presence of these antibodies in patients with IIM patients is
      not clinically relevant in our cohort.

PMID- 30116553
TI  - RFamidergic neurons in the olfactory centers of the terrestrial slug Limax.
AB  - Background: The terrestrial slug Limax has long been used as a model for the
      study of olfactory information processing and odor learning. Olfactory inputs
      from the olfactory epithelium are processed in the tentacular ganglion and then
      in the procerebrum. Glutamate and acetylcholine are the major neurotransmitters
      used in the procerebrum. Phe-Met-Arg-Phe-NH2 (FMRFamide) has been shown to be
      involved in the regulation of the network activity of the procerebrum. Although
      there are thought to be various RFamide family peptides other than FMRFamide that
      are potentially recognized by anti-FMRFamide antibody in the central nervous
      system of mollusks, identifying the entire repertoire of RFamide peptides in
      Limax has yet to be achieved. Methods: In the present study, we made a
      comprehensive search for RFamide peptide-encoding genes from the transcriptome
      data of Limax, and identified 12 genes. The expression maps of these RFamide
      genes were constructed by in situ hybridization in the cerebral ganglia including
      the procerebrum, and in the superior/inferior tentacles. Results: Ten of 12 genes
      were expressed in the procerebrum, and nine of 12 genes were expressed in the
      tentacular ganglia. Gly-Ser-Leu-Phe-Arg-Phe-NH2 (GSLFRFamide), which is encoded
      by two different genes, LFRFamide1 (Leu-Phe-Arg-Phe-NH2-1) and LFRFamide2 (Leu
      Phe-Arg-Phe-NH2-2), decreased the oscillatory frequency of the local field
      potential oscillation in the procerebrum when exogenously applied in vitro. We
      also found by immunohistochemistry that the neurons expressing pedal peptide send
      efferent projections from the procerebrum back to the tentacular ganglion.
      Conclusion: Our findings suggest the involvement of a far wider variety of
      RFamide family peptides in the olfactory information processing in Limax than
      previously thought.

PMID- 30116557
TI  - Crystal structure of 3,14-dimethyl-2,6,13,17-tetra-azoniatri-cyclo
      [16.4.0.07,12]docosane tetra-chloride tetra-hydrate from synchrotron X-ray data.
AB  - The crystal structure of the title salt, C20H44N44+.4Cl-.4H2O, has been
      determined using synchrotron radiation at 220 K. The structure determination
      reveals that protonation has occurred at all four amine N atoms. The asymmetric
      unit contains one half-cation (completed by crystallographic inversion symmetry),
      two chloride anions and two water mol-ecules. There are two mol-ecules in the
      unit cell. The Cl- anions and hydrate mol-ecules are involved in hydrogen
      bonding. The crystal structure is stabilized by inter-molecular hydrogen bonds
      involving the macrocycle N-H groups and water O-H groups as donors and the O
      atoms of the water mol-ecules and the Cl- anions as acceptors, giving rise to a
      three-dimensional network.

PMID- 30116556
TI  - Methods to improve medication adherence in patients with chronic inflammatory
      rheumatic diseases: a systematic literature review.
AB  - Objective: Lack of adherence to treatment is frequent in chronic inflammatory
      rheumatic diseases and is associated with poorer outcomes. The objective of this
      study was to describe and evaluate interventions that have been proposed to
      enhance medication adherence in these conditions. Methods: A systematic
      literature review was performed in Pubmed, Cochrane, Embase and
      clinicaltrials.gov databases completed by the rheumatology meeting (ACR, EULAR
      and SFR) abstracts from last 2 years. All studies in English or French evaluating
      an intervention to improve medication adherence in chronic inflammatory rheumatic
      diseases (rheumatoid arthritis (RA), spondyloarthritis (SpA), crystal related
      diseases, connective tissue diseases, vasculitis and Still's disease) were
      included. Interventions on adherence were collected and classified in five
      modalities (educational, behavioural, cognitive behavioural, multicomponent
      interventions or others). Results: 1325 abstracts were identified and 22 studies
      were finally included (18 studies in RA (72%), 4 studies in systemic lupus
      erythematosus (16%), 2 studies in SpA (8%) and 1 study in gout (4%)). On 13
      randomised controlled trials (RCT) (1535 patients), only 5 were positive (774
      patients). Educational interventions were the most represented and had the
      highest level of evidence: 8/13 RCT (62%, 1017 patients) and 4/8 were positive
      (50%). In these studies, each patient was individually informed or educated by
      different actors (physicians, pharmacists, nurses and so on). Supports and
      contents of these educational interventions were heterogenous. Conclusion:
      Despite the importance of medication adherence in chronic inflammatory rheumatic
      disorders, evidence on interventions to improve medication adherence is scarce.

PMID- 30116558
TI  - A strongly fluorescent NiII complex with 2-(2-hy-droxy-eth-yl)pyridine ligands:
      synthesis, characterization and theoretical analysis and comparison with a
      related polymeric CuII complex.
AB  - The synthesis and characterization of di-aqua-bis-[2-(2-hy-droxy-eth-yl)pyridine
      kappa2N,O)nickel(II) dinitrate, [Ni(C7H9NO)2(H2O)2](NO3)2, under ambient
      conditions is reported and compared with catena-poly[[bis-[2-(2-hy-droxy-eth
      yl)pyridine-kappa2N,O]copper(II)]-MU-sulfato-kappa2O:O'], [Cu(C7H9NO)2(SO4)] n
      [Zegh-ouan et al. (2016 ?). Private communication (refcode 1481676). CCDC,
      Cambridge, England]. In the two complexes, the 2-(2-hy-droxy-eth-yl)pyridine
      ligands coordinate the metal ions through the N atom of the pyridine ring and the
      O atom of the hy-droxy group, creating a chelate ring. The NiII or CuII ion lies
      on an inversion centre and exhibits a slightly distorted MO4N2 octa-hedral
      coordination geometry, build up by O and N atoms from two 2-(2-hy-droxy-eth
      yl)pyridine ligands and two water mol-ecules or two O atoms belonging to sulfate
      anions. The sulfate anion bridges the CuII ions, forming a polymeric chain. The
      photoluminescence properties of these complexes have been studied on as
      synthesized samples and reveal that both compounds display a strong blue-light
      emission with maxima around 497 nm. From DFT/TDDFT studies, the blue emission
      appears to be derived from the ligand-to-metal charge-transfer (LMCT) excited
      state. In addition, the IR spectroscopic properties and thermogravimetric
      behaviours of both complexes have been investigated.

PMID- 30116559
TI  - Two N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicarboxamide coordination compounds.
AB  - The molecular structures of tetra-aqua-[N,N'-bis-(pyridin-4-yl)pyridine-2,6-dicar
      boxamide]-sulfatomanganese(II) dihydrate, [Mn(SO4)(C17H13N5O2)(H2O)4].2H2O or
      [Mn(H2L1)(SO4)(H2O)4].2H2O, (I), and tetra-aqua-bis[N,N'-bis-(pyridin-4
      yl)pyridine-2,6-dicar-boxamide]cadmium(II) sulfate tetra-hydrate,
      [Cd(C17H13N5O2)2(H2O)4]SO4.4H2O or [Cd(H2O)4(H2L1)2].SO4.4H2O, (II), both contain
      a central metal atom in a distorted octa-hedral geometry coordinated equatorially
      by four oxygen atoms from water mol-ecules. In (I), the axial positions are
      occupied by a nitro-gen atom from H2L1 and an oxygen atom from the sulfate anion,
      whereas in (II), the axial positions contain two nitro-gen atoms from two
      different H2L1 ligands and the sulfate anion acts as the charge-balancing ion. pi
      pi stacking between pyridine rings and a network of hydrogen bonds involving the
      water molecules and the sulfate anions play a crucial role in the mol-ecular self
      assembly of the two structures.

PMID- 30116560
TI  - Crystal structure of aqua-(2-{[2-({2-[bis-(carboxyl-ato-kappaO-meth-yl)amino
      kappaN]eth-yl}(carboxyl-ato-kappaO-meth-yl)amino-kappaN)eth-yl](carb-oxy-meth
      yl)aza-niumyl}acetato)-gallium(III) trihydrate.
AB  - In the title GaIII complex compound with pentetic acid,
      [Ga(C14H20N3O10)(H2O)].3H2O, the GaIII centre is bound in a slightly distorted
      octa-hedral coordination sphere by two amine N atoms, three carboxyl-ate O atoms
      and one water O atom. The complex mol-ecule exists as a zwitterion. In the
      crystal, the complexes are linked to each other via O-H?O and C-H?O hydrogen
      bonds, forming layers parallel to (001). Three uncoordinating water mol-ecules
      link the complex layers via O-H?O, N-H?O and C-H?O hydrogen bonds, forming a
      three-dimensional network.

PMID- 30116561
TI  - (2R,3R)-1,4-Dioxa-spiro-[4.4]nonane-2,3-di-carb-oxy-lic and (2R,3R)-1,4-dioxa
      spiro-[4.5]decane-2,3-di-carb-oxy-lic acids.
AB  - The title compounds, C9H12O6 and C10H14O6, were formed by careful hydrolysis of
      the corresponding diethyl esters. Their single crystals were grown from an ethyl
      acetate/hexane mixture. Crystals of both compounds have monoclinic (P21) symmetry
      with a single mol-ecule in the asymmetric unit. Both crystal structures are very
      similar and display four -CO-OH?O=C(OH)- hydrogen bonds, forming a two
      dimensional double-layered framework.

PMID- 30116562
TI  - Crystal structure and Hirshfeld surface analysis of (2E)-3-(3-bromo-4-fluoro-phen
      yl)-1-(3,4-di-meth-oxy-phen-yl)prop-2-en-1-one.
AB  - In the mol-ecule of the title compound, C17H14BrFO3, the aromatic rings are
      tilted with respect to the enone bridge by 13.63 (14) and 4.27 (15) degrees , and
      form a dihedral angle 17.91 (17) degrees . In the crystal, centrosymmetrically
      related mol-ecules are linked by pairs of C-H?O hydrogen bonds into dimeric
      units, forming rings of R22(14) graph-set motif. The dimers are further connected
      by weak C-H?O hydrogen inter-actions, forming layers parallel to (10). Hirshfeld
      surface analysis shows that van der Waals inter-actions constitute the major
      contribution to the inter-molecular inter-actions, with H?H contacts accounting
      for 29.7% of the surface.

PMID- 30116563
TI  - Redetermination of the solvent-free crystal structure of l-proline.
AB  - The title compound, (S)-pyrrolidine-2-carb-oxy-lic acid (C5H9NO2), commonly known
      as l-proline, crystallized without the inclusion of any solvent or water mol
      ecules through the slow diffusion of diethyl ether into a saturated solution of l
      proline in ethanol. l-Proline crystallized in its zwitterionic form and the mol
      ecules are linked via N-H?O hydrogen bonds, resulting in a two-dimensional
      network. In comparison to the only other publication of a single-crystal
      structure of l-proline without inclusions [Kayushina & Vainshtein (1965 ?).
      Kristallografiya, 10, 833-844], the R1 value is significantly improved (0.039
      versus 0.169) and thus, our data provides higher precision structural
      information.

PMID- 30116564
TI  - The crystal structure of (E)-2-ethyl-N-(4-nitro-benzyl-idene)aniline: three
      dimensional supra-molecular assembly mediated by C-H?O hydrogen bonds and
      nitro?pi(arene) inter-actions.
AB  - In the mol-ecule of the title compound, C15H14N2O2, the 2-ethyl-phenyl group is
      disordered over two sets of atomic sites having occupancies of 0.515 (19) and
      0.485 (19), and the dihedral angle between the two partial-occupancy aryl rings
      is 6(2) degrees . A combination of C-H?O hydrogen bonds and nitro?pi(arene) inter
      actions links the mol-ecules into a continuous three-dimensional framework
      structure. Comparisons are made with the structures of some related compounds.

PMID- 30116565
TI  - Crystal structure of a seven-coordinate manganese(II) complex with tris-(pyridin
      2-ylmeth-yl)amine (TMPA).
AB  - Structural analysis of (acetato-kappa2O,O')(methanol-kappaO)[tris-(pyridin-2
      ylmeth-yl)amine-kappa4N,N',N'',N''']manganese(II) tetraphenyl-borate,
      [Mn(C2H3O2)(C18H18N4)(CH3OH)](C24H20B) or [Mn(TMPA)(Ac)(CH3OH)]BPh4 [TMPA = tris
      (pyridin-2-ylmeth-yl)amine, Ac = acetate, BPh4 = tetra-phenyl-borate] by single
      crystal X-ray diffraction reveals a complex cation with tetra-dentate
      coordination of the tripodal TMPA ligand, bidentate coordination of the Ac ligand
      and monodentate coordination of the methanol ligand to a single MnII center,
      balanced in charge by the presence of a tetra-phenyl-borate anion. The MnII
      complex has a distorted penta-gonal-bipyramidal geometry, in which the central
      amine nitro-gen and two pyridyl N atoms of the TMPA ligand, and two oxygen atoms
      of the acetate ligand occupy positions in the penta-gonal plane, while the third
      pyridyl nitro-gen of TMPA and the oxygen from the methanol ligand occupy the
      axial positions. Within the complex, the acetate O atoms participate in weak C
      H?O hydrogen-bonding inter-actions with neighboring pyridyl moieties. In the
      crystal, complexes form dimers by pairs of O-H?O hydrogen bonds between the
      coordinated methanol of one complex and an acetate oxygen of the other, and weak
      pi-stacking inter-actions between pyridine rings. Separate dimers then undergo
      additional pi-stacking inter-actions between the pyridine rings of one moiety and
      either the pyridine or phenyl rings of another moiety that further stabilize the
      crystal.

PMID- 30116566
TI  - Crystal structure and Hirshfeld surface analysis of ethyl (E)-4-[(4-hy-droxy-3
      meth-oxy-5-nitro-benzyl-idene)amino]-benzoate.
AB  - The title Schiff base compound, C17H16N2O6, has an E configuration with respect
      to the C=N bond, with a dihedral angle between the two benzene rings of 31.90
      (12) degrees . There is an intra-molecular O-H?Onitro hydrogen bond present
      forming an S(6) ring motif. In the crystal, mol-ecules are linked by pairs of O
      H?O hydrogen bonds, forming inversion dimers enclosing an R22(4) ring motif. The
      dimers are linked about an inversion centre by pairs of C-H?O hydrogen bonds,
      which enclose R22(22) loops, forming chains propagating along the [10] direction.
      Hirshfeld surface analysis and fingerprint plots show enrichment ratios for the
      H?H, O?H and C?H contacts, indicating a high propensity of such inter-actions in
      the crystal. Both the nitro group and the CH3-CH2-O- group are positionally
      disordered.

PMID- 30116567
TI  - Crystal structure of limonoid TS3, isolated from Trichilia rubescens.
AB  - The title limonoid compound, C26H28O5.0.5H2O (TS3) [systematic name:
      (3aS,3bS,4aS,5aS,6S,7aR,8aR,8bS,11aR)-6-(furan-3-yl)-3a,5a,8b,11a-tetra-methyl
      3a,4a,5,5a,6,7,7a,8b,11,11a-deca-hydro
      oxireno[2',3':4b,5]oxireno[2'',3'':2',3']cyclo-penta-[1',2':7,8]phenanthro[10,1
      bc]furan-3(3aH)-one hemihydrate], crystallizes with two independent mol-ecules (1
      and 2) in the asymmetric unit and one water mol-ecule. TS3 is composed of three
      six-membered rings (A, C and D), three five-membered rings (B, E and F) and two
      epoxide rings. A group of five fused rings (A-E) is bonded to a furan ring (F)
      with a Csp3-Csp2 bond [1.500 (3) A in mol-ecule 1 and 1.499 (3) A in mol-ecule
      2]. The absolute structures of the mol-ecules in the crystal were determined by
      resonant scattering; Flack parameter = 0.05 (5). In the crystal, the individual
      mol-ecules stack in columns along the b-axis direction. The water mol-ecule
      bridges mol-ecules 1 and 2 via Owater-H?O and C-H?Owater hydrogen bonds. Together
      with further C-H?O hydrogen bonds, linking mol-ecules 1 and 2, the columns are
      linked to form slabs parallel to the ab plane. Within each column, mol-ecules are
      also linked via C-H?pi inter-actions involving the five-membered furan (F) rings.

PMID- 30116568
TI  - Mol-ecular structure, DFT studies and UV-Vis absorption of two new linear fused
      ring chalcones: (E)-1-(anthracen-9-yl)-3-(2-meth-oxy-phen-yl)prop-2-en-1-one and
      (E)-1-(anthracen-9-yl)-3-(3-fluoro-4-meth-oxy-phen-yl)prop-2-en-1-one.
AB  - The title compounds, C24H18O2 and C24H17FO2, were synthesized using the Claisen
      Schmidt condensation method and characterized by UV-Vis spectroscopy. Weak inter
      molecular C-H?O, C-H?pi and pi-pi hydrogen-bonding inter-actions help to
      stabilize the crystal structures of both compounds. The geometrical parameters
      obtained from the mol-ecular structure were optimized using density functional
      theory (DFT) calculations at the B3LYP/6-311++G(d,p) level, showing a good
      correlation with the experimental results. The small HOMO-LUMO energy gaps of
      3.11 and 3.07 eV enhances the non-linear responses of these mol-ecular systems.

PMID- 30116570
TI  - Crystal structure of a dinuclear ruthenium(II) complex with a bent CO22- bridge.
AB  - The mol-ecular and crystal structures of a CO22--bridged dinuclear ruthenium
      complex is reported, namely, MU-carbonito-kappa2C:O-bis-[bis(2,2'-bi-pyridine
      kappa2N,N')carbon-ylruthenium(II)] bis-(hexa-fluorido-phosphate)-aceto-nitrile
      diethyl ether (1/1/0.5), [Ru2(CO)2(C10H8N2)4(MU:kappa2-C:O
      CO2)](PF6)2.CH3CN.0.5C4H10O. The complex cation in the title compound consists of
      two {Ru(CO)(bpy)2}2+ units (bpy = 2,2'-bi-pyridine) singly bridged by a MU:kappa2
      C:O carbonite anion, resulting in an unsymmetrical dinuclear structure. Some of
      the inter-atomic C?O distances involving the carbonyl ligands are shorter than
      the sum of the van der Waals radii. There are intra-molecular C-H?O and aromatic
      pi-pi contacts in the cationic complex. In the crystal, the cations are linked by
      pairs of C-H?F hydrogen bonds in addition to weak C-H?F inter-actions between the
      solvent mol-ecules and PF6- counter-anions. The equatorial F atoms of one of the
      PF6- anions are disordered over two sets of sites with an occupancy ratio of
      0.908 (7):0.092 (7) while the central O atom of the diethyl ether solvent mol
      ecule is disordered over an inversion centre.

PMID- 30116569
TI  - Crystal structures of dimethyl 5-iodo-iso-phthal-ate and dimethyl 5-ethynyl-iso
      phthal-ate.
AB  - In dimethyl 5-iodo-isophthalate, C10H9IO4, (I), the planes through the methyl
      carboxyl-ate moieties are tilted with respect to the benzene ring, whereas the
      mol-ecular framework of dimethyl 5-ethynylisophthalate, C12H10O4, (II), is
      perfectly planar. The crystal structure of (I) is stabilized by a three
      dimensional supra-molecular network comprising C-H?O=C hydrogen bonds, as well as
      I?O=C inter-actions. In the crystal of (II), the mol-ecules are connected via C
      Hethyn-yl?O=C hydrogen bonds to infinite strands. Moreover, pi-pi arene stacking
      inter-actions connect the mol-ecular chains into two-dimensional supra-molecular
      aggregates.

PMID- 30116571
TI  - Three-component reaction between isatoic anhydride, amine and meth-yl-subs
      tituted furyl-acryl-alde-hydes: crystal structures of 3-benzyl-2-[(E)-2-(5
      methylfuran-2-yl)vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one, 3-benzyl-2-[(E)-2
      (furan-2-yl)-1-methyl-vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one and 3-(furan-2
      ylmeth-yl)-2-[(E)-2-(furan-2-yl)-1-methyl-vin-yl]-2,3-di-hydro-quinazolin-4(1H)
      one.
AB  - Compounds (I), C22H20N2O2, (II), C22H20N2O2 and (III), C20H18N2O3 are the
      products of three-component reactions between isatoic anhydride, the
      corresponding amine and 3-(5-methylfuran-2-yl)- or (furan-2-yl)-2-methyl-acryl
      aldehyde. Compound (I) crystallizes in the monoclinic space group P21/n, while
      compounds (II) and (III) are isostructural and crystallize in the ortho-rhom-bic
      space group Pbca. The tetra-hydro-pyrimidine ring in (I)-(III) adopts a sofa
      conformation. The NH nitro-gen atom has a trigonal-pyramidal geometry, whereas
      the N(R) nitro-gen atom is flattened. The furyl-vinyl substituents in (I)-(III)
      are practically planar and have an E configuration at the C=C double bond. In
      (I), this bulky fragment occupies the axial position at the quaternary carbon
      atom of the tetra-hydro-pyrimidine ring, whereas in (II) and (III) it is
      equatorially disposed. In the crystal of (I), mol-ecules form hydrogen-bonded
      chains propagating along [001] by strong inter-molecular N-H?O hydrogen bonds.
      The chains are packed in stacks along the a-axis direction. In the crystals of
      (II) and (III), mol-ecules also form hydrogen-bonded chains propagating along
      [100] by strong inter-molecular N-H?O hydrogen bonds. However, despite the fact
      that compounds (II) and (III) are isostructural, steric differences between the
      phenyl and furyl substituents result in chains with different geometries. Thus in
      the crystal of (II) the chains have a zigzag-like structure, whereas in the
      crystal of (III), they are almost linear. In both (II) and (III), the hydrogen
      bonded chains are further packed in stacks along the b-axis direction.

PMID- 30116572
TI  - Crystal structure of {(E)-2-[(3,4-di-meth-oxy-phenyl-imino)-meth-yl]phenolato
      kappa2N,O1}bis-[2-(pyridin-2-yl)phenyl-kappa2C1,N]iridium(III) di-chloro-methane
      disolvate.
AB  - The asymmetric unit of the solvated title complex,
      [Ir(C11H8N)2(C15H14NO3)].2CH2Cl2, consists of two complex mol-ecules together
      with four di-chloro-methane solvent mol-ecules, one of which is disordered. In
      each complex mol-ecule, the IrIII ion has a distorted octa-hedral coordination
      environment defined by two 2-phenyl-pyridine ligands, through two phenyl C and
      two pyridine N atoms, and by one N,O-bidentate 2-[(2,4-di-meth-oxy-phenyl-imino)
      meth-yl]phenolate anion. The IrIII ions lie almost in the equatorial planes with
      deviations of 0.0396 (17) and 0.0237 (17) A, respectively, for the two complex
      mol-ecules. In both complex mol-ecules, the two 2-phenyl-pyridine ligands are
      nearly perpendicular to each other [dihedral angles between the least-squares
      planes of 89.91 (11) and 85.13 (11) degrees ]. In the crystal, inter-molecular C
      H?O inter-actions as well as inter-molecular C-H?pi inter-actions are present,
      leading to a three-dimensional network structure. One of the four dichlormethane
      solvent mol-ecules shows disorder over two sets of sites [occupancy ratio 0.79
      (2):0.21 (2)].

PMID- 30116573
TI  - Crystal structures of 2-amino-pyridine citric acid salts: C5H7N2+.C6H7O7- and
      3C5H7N2+.C6H5O73.
AB  - 2-Amino-pyridine and citric acid mixed in 1:1 and 3:1 ratios in ethanol yielded
      crystals of two 2-amino-pyridinium citrate salts, viz. C5H7N2+.C6H7O7- (I)
      (systematic name: 2-amino-pyridin-1-ium 3-carb-oxy-2-carb-oxy-methyl-2-hy-droxy
      propano-ate), and 3C5H7N2+.C6H5O73- (II) [systematic name: tris-(2-amino-pyridin
      1-ium) 2-hy-droxy-propane-1,2,3-tri-carboxyl-ate]. The supra-molecular synthons
      present are analysed and their effect upon the crystal packing is presented in
      the context of crystal engineering. Salt I is formed by the protonation of the
      pyridine N atom and deprotonation of the central carb-oxy-lic group of citric
      acid, while in II all three carb-oxy-lic groups of the acid are deprotonated and
      the charges are compensated for by three 2-amino-pyridinium cations. In both
      structures, a complex supra-molecular three-dimensional architecture is formed.
      In I, the supra-molecular aggregation results from Namino-H?Oacid, Oacid?H-Oacid,
      Oalcohol-H?Oacid, Namino-H?Oalcohol, Npy-H?Oalcohol and Car-H?Oacid inter
      actions. The mol-ecular conformation of the citrate ion (CA3-) in II is
      stabilized by an intra-molecular Oalcohol-H?Oacid hydrogen bond that encloses an
      S(6) ring motif. The complex three-dimensional structure of II features Namino
      H?Oacid, Npy-H?Oacid and several Car-H?Oacid hydrogen bonds. In the crystal of I,
      the common charge-assisted 2-amino-pyridinium-carboxyl-ate heterosynthon
      exhibited in many 2-amino-pyridinium carboxyl-ates is not observed, instead
      chains of N-H?O hydrogen bonds and hetero O-H?O dimers are formed. In the crystal
      of II, the 2-amino-pyridinium-carboxyl-ate heterosynthon is sustained, while
      hetero O-H?O dimers are not observed. The crystal structures of both salts
      display a variety of hydrogen bonds as almost all of the hydrogen-bond donors and
      acceptors present are involved in hydrogen bonding.

PMID- 30116574
TI  - Single-crystal X-ray diffraction study of a host-guest system comprising
      monofunctionalized-hydroxy pillar[5]arene and 1-octa-namine.
AB  - Co-crystallization of a monofunctionalized hy-droxy pillar[5]arene with 1-octa
      namine resulted in the formation of an inclusion complex where the alkyl chain is
      threaded in the macrocycle cavity, namely 1,2,3,4-(1,4-dimeth-oxy)-5-(1-hy-droxy
      4-meth-oxy)-pillar[5]arene-1-octa-namine-water (1/1/1), C44H48O10.C8H19N.H2O. The
      guest compound is stabilized inside the cavity by hydrogen-bonding and C-H?pi
      inter-actions. The water mol-ecule in the asymmetric unit mediates the formation
      of a supra-molecular dimer by hydrogen-bonding inter-actions. These
      functionalized-pillararene hosts expand the possibility of exploring more supra
      molecular inter-actions with various guest species.

PMID- 30116575
TI  - The crystal structure of bis-[(E)-4-bromo-2-({[2-(pyridin-2-yl)eth-yl]imino}-meth
      yl)phenol]nickel(II) bis-[(E)-4-bromo-2-({[2-(pyridin-2-yl)eth-yl]imino}-meth
      yl)phenolato]nickel(II) bis(perchlorate) methanol monosolvate, a structure
      containing strong inter-species hydrogen bonds.
AB  - The title compound, [Ni(C14H12BrN2O)2][Ni(C14H13BrN2O)2](ClO4)2.CH3OH consists of
      two mononuclear ([Ni(HL)2]2+ and [NiL2]) complex mol-ecules linked by strong
      hydrogen bonding [O?O separations of only 2.430 (5) A], which is the shortest
      reported to date for such species. In one of the complexes, both the coordinated
      phen-oxy groups retain their protons and thus this is the cationic equivalent
      species of the other complex where both coordinated phen-oxy groups are
      deprotonated. In addition, perchlorate anions are present for charge balance, as
      well as methanol solvate mol-ecules. For the neutral NiL2 complex, each 2-ethyl
      amine-pyridine arm is disordered over two equivalent conformations with
      occupancies of 0.750 (8):0.250 (8). The perchlorate anion is disordered over two
      equivalent conformations with occupancies of 0.602 (8):0.398 (8). The perchlorate
      ions also link to the H atoms on the methanol methyl and hydroxyl groups. These
      inter-actions link the moieties into a complex three-dimensional array. The
      crystal studied was refined as a two-component twin.

PMID- 30116576
TI  - Crystal structure of N-allyl-4-methyl-benzene-sulfonamide.
AB  - The title compound, C10H13NO2S, was synthesized by a nucleophilic substitution
      reaction between allyl amine and p-toluene-sulfonyl chloride. The sulfonate S-O
      bond lengths are 1.4282 (17) and 1.4353 (17) A, and the C-N-S-C torsion angle
      involving the sulfonamide moiety is -61.0 (2) degrees . In the crystal,
      centrosymmetric dimers of the title compound are present via inter-molecular N
      H?O hydrogen bonds between sulfonamide groups. These dimers are linked into
      ribbons along the c-axis direction through offset pi-pi inter-actions.

PMID- 30116577
TI  - Structural analysis of 2-iodo-benzamide and 2-iodo-N-phenyl-benzamide.
AB  - The title compounds, 2-iodo-benzamide, C7H6INO (I), and 2-iodo-N-phenyl
      benzamide, C13H10INO (II), were both synthesized from 2-iodo-benzoic acid. In the
      crystal structure of (I), N-H?O and hydrogen bonds form two sets of closed rings,
      generating dimers and tetra-mers. These combine with C-I?pi(ring) halogen bonds
      to form sheets of mol-ecules in the bc plane. For (II), N-H?O hydrogen bonds form
      chains along the a-axis direction, while inversion-related C-I?pi(ring) contacts
      supported by C-H?pi(ring) interactions generate sheets of mol-ecules along the ab
      diagonal.

PMID- 30116578
TI  - Crystal structure and Hirshfeld surface analysis of (E)-3-(2-chloro-4-fluoro-phen
      yl)-1-(2,5-di-chloro-thio-phen-3-yl)prop-2-en-1-one.
AB  - In the title chalcone-thio-phene derivative, C13H6Cl3FOS, the aromatic rings are
      inclined to one another by 12.9 (2) degrees , and the thio-phene ring is affected
      by pi-conjugation. In the crystal, mol-ecules are linked by C-H?F hydrogen bonds,
      forming an R22(8) ring motif. A Hirshfeld surface analysis was conducted to
      verify the contribution of the different inter-molecular inter-actions. The shape
      index surface clearly shows that the two sides of the mol-ecules are involved in
      the same contacts with neighbouring mol-ecules and the curvedness plots show flat
      surface patches characteristic of planar stacking.

PMID- 30116579
TI  - Crystal structure of a mononuclear copper(II) complex with 2-methoxy-N,N-bis
      (quinolin-2-yl-meth-yl)-ethyl-amine (DQMEA).
AB  - Structural characterization of the compound [Cu(C2H3N)(C23H23N3O)](ClO4)2] or
      [Cu(C2H3N)(DQMEA)](ClO4)2] [DQMEA = 2-methoxy-N,N-bis-(quinolin-2-ylmeth-yl)ethyl
      amine] {systematic name: (aceto-nitrile)[2-methoxy-N,N-bis(quinolin-2-ylmeth
      yl)ethyl-amine]-copper(II) diperchlorate} by single-crystal X-ray diffraction
      reveals a complex cation with a tetra-dentate coordination of the DQMEA ligand
      along with monodentate coordination of a CH3CN ligand to a single CuII center,
      with two perchlorate anions providing charge balance. The CuII center has a
      distorted square-pyramidal geometry in which the nitro-gen atoms of the DQMEA and
      CH3CN ligands occupy the equatorial positions, while the oxygen atom of the DQMEA
      ligand resides in the axial position with an elongated Cu-O bond. The quinoline
      ring systems are nearly co-planar in the structure, while the linear CH3CN ligand
      is tilted significantly below this plane, and the central nitro-gen of DQMEA is
      above it. Within the complex, weak C-H?N hydrogen bonding takes place between the
      nitro-gen of CH3CN and a neighboring quinolyl group. The perchlorate ions are
      disordered within the structure, but undergo a number of weak inter-molecular C
      H?O hydrogen-bonding inter-actions. Additional weak pi-stacking inter-actions
      between the quinolyl groups of neighboring complexes further stabilize the
      crystal packing.

PMID- 30116580
TI  - Crystal structures of 2-bromo-1,1,1,3,3,3-hexa-methyl-2-(tri-methyl-sil-yl)tris
      ilane and 2-bromo-1,1,1,3,3,3-hexa-isopropyl-2-(triiso-propyl-sil-yl)tri-silane.
AB  - The synthesis and crystal structures of two tris-(tri-alkyl-sil-yl)silyl bromide
      compounds, C9H27BrSi4 (I, HypSiBr) and C27H63BrSi4 (II, TipSiBr), are described.
      Compound I was prepared in 85% yield by free-radical bromination of 1,1,1,3,3,3
      hexa-methyl-2-(tri-methyl-sil-yl)tris-ilane using bromo-butane and 2,2'-azobis(2
      methyl-propio-nitrile) as a radical initiator at 333 K. The mol-ecule possesses
      threefold rotational symmetry, with the central Si atom and the Br atom being
      located on the threefold rotation axis. The Si-Br bond distance is 2.2990 (12) A
      and the Si-Si bond lengths are 2.3477 (8) A. The Br-Si-Si bond angles are 104.83
      (3) degrees  and the Si-Si-Si bond angles are 113.69 (2) degrees , reflecting the
      steric hindrance inherent in the three tri-methyl-silyl groups attached to the
      central Si atom. Compound II was prepared in 55% yield by free-radical
      bromination of 1,1,1,3,3,3-hexa-isopropyl-2-(triiso-propyl-sil-yl)tris-ilane
      using N-bromo-succinimide and 2,2'-azobis(2-methyl-propio-nitrile) as a radical
      initiator at 353 K. Here the Si-Br bond length is 2.3185 (7) A and the Si-Si bond
      lengths range from 2.443 (1) to 2.4628 (9) A. The Br-Si-Si bond angles range from
      98.44 (3) to 103.77 (3) degrees , indicating steric hindrance between the three
      triiso-propyl-silyl groups.

PMID- 30116581
TI  - Crystal structure and Hirshfeld surface analysis of N,N'-bis-(3-tert-butyl-2-hy
      droxy-5-methyl-benzyl-idene)ethane-1,2-di-amine.
AB  - The title compound, C26H36N2O2, crystallizes in the phenol-imine form. In the mol
      ecule, there are intra-molecular O-H?N hydrogen bonds forming S(6) ring motifs,
      and the two aromatic rings are inclined to each other by 37.9 (7) degrees . In
      the crystal, mol-ecules are linked by pairs of weak C-H?O hydrogen bonds, forming
      inversion dimers. Hirshfeld surface analysis and two-dimensional fingerprint
      plots indicate that the most important contributions to the crystal packing are
      from H?H (77.5%), H?C/C?H (16%), H?O/O?H (3.1%) and H?N/N?H (1.7%) inter-actions.

PMID- 30116582
TI  - {N1-[2-(Butyl-selan-yl)benz-yl]-N2,N2-di-methyl-ethane-1,2-di-amine}-dichlorido
      mercury(II).
AB  - In the title compound, [HgCl2(C16H28N2Se)], the primary geometry around the Se
      and Hg atoms is distorted trigonal-pyramidal and distorted square-pyramidal,
      respectively. The distortion of the mol-ecular geometry in the complex is caused
      by the steric demands of the ligands attached to the Se atom. The Hg atom is
      coordinated through two chloride anions, an N atom and an Se atom, making up an
      unusual HgNSeCl2 coordination sphere with an additional long Hg?N inter-action.
      Inter-molecular C-H?Cl inter-actions are the only identified inter-molecular
      hydrogen-bonding inter-actions that seem to be responsible for the self assembly.
      These relatively weak C-H?Cl hydrogen bonds possess the required linearity and
      donor-acceptor distances. They act as mol-ecular associative forces that result
      in a supra-molecular assembly along the b-axis direction in the solid state of
      the title compound.

PMID- 30116583
TI  - Crystal structure of disilver(I) dizinc(II) iron(III) tris-(orthovanadate) with
      an alluaudite-type structure.
AB  - The title compound, Ag2Zn2Fe(VO4)3, has been synthesized by solid-state reactions
      and belongs to the alluaudite structure family. In the crystal structure, four
      sites are positioned at special positions. One silver site is located on an
      inversion centre (Wyckoff position 4b), and an additional silver site, as well as
      one zinc and one vanadium site, on twofold rotation axes (4e). One site on a
      general position is statistically occupied by FeIII and ZnII cations that are
      octa-hedrally surrounded by O atoms. The three-dimensional framework structure of
      the title vanadate results from [(Zn,Fe)2O10] units of edge-sharing [(Zn,Fe)O6]
      octa-hedra that alternate with [ZnO6] octa-hedra so as to form infinite chains
      parallel to [10]. These chains are linked through VO4 tetra-hedra by sharing
      vertices, giving rise to layers extending parallel to (010). Such layers are
      shared by common vanadate tetra-hedra. The resulting three-dimensional framework
      delimits two types of channels parallel to [001] in which the silver sites are
      located with four- and sixfold coordination by oxygen.

PMID- 30116584
TI  - Crystal structure and Hirshfeld surface analysis of 2,4-di-amino-6-phenyl-1,3,5
      triazin-1-ium 4-methyl-benzene-sulfonate.
AB  - In the title mol-ecular salt, C9H10N5+.C7H7O3S-, the asymmetric unit consists of
      a 2,4-di-amino-6-phenyl-1,3,5-triazin-1-ium cation and a 4-methyl-benzene
      sulfonate anion. The cation is protonated at the N atom lying between the amine
      and phenyl substituents. The protonated N and amino-group N atoms are involved in
      hydrogen bonding with the sulfonate O atoms through a pair of inter-molecular N
      H?O hydrogen bonds, giving rise to a hydrogen-bonded cyclic motif with R22(8)
      graph-set notation. The inversion-related mol-ecules are further linked by four N
      H?O inter-molecular inter-actions to produce a complementary DDAA (D = donor, A =
      acceptor) hydrogen-bonded array, forming R22(8), R42(8) and R22(8) ring motifs.
      The centrosymmetrically paired cations form R22(8) ring motifs through base
      pairing via N-H?N hydrogen bonds. In addition, another R33(10) motif is formed
      between centrosymetrically paired cations and a sulfonate anion via N-H?O
      hydrogen bonds. The crystal structure also features weak S=O?pi and pi-pi inter
      actions. Hirshfeld surface and fingerprint plots were employed in order to
      further study the inter-molecular inter-actions.

PMID- 30116585
TI  - M+M3+2As(HAsO4)6 (M+M3+ = TlGa, CsGa, CsAl): three new metal arsenates containing
      AsO6 octa-hedra.
AB  - The crystal structures of hydro-thermally synthesized (T = 493 K, 7 d)
      thallium(I) digallium arsenic(V) hexa-kis-[hydrogenarsenate(V)], TlGa2As(HAsO4)6,
      caes-ium digallium arsenic(V) hexa-kis-[hydrogenarsenate(V)], CsGa2As(HAsO4)6,
      and caesium dialuminium arsenic(V) hexa-kis-[hydrogenarsenate(V)],
      CsAl2As(HAsO4)6, were solved by single-crystal X-ray diffraction. The three
      compounds are isotypic and adopt the structure type of RbAl2As(HAsO4)6 (Rc),
      which itself represents a modification of the RbFe(HPO4)2 structure type and
      consists of a tetra-hedral-octa-hedral framework in which the slightly disordered
      M+ cations are located in channels. The three new compounds contain AsO6 octa
      hedra assuming the topological role of M3+O6 octa-hedra. The As-O bond lengths
      are among the shortest As-O bond lengths known so far in AsO6 octa-hedra.

PMID- 30116586
TI  - Crystal structure and Hirshfeld surface analysis of (E)-3-[(2,3-di-chloro-benzyl
      idene)amino]-5-phenyl-thia-zolidin-2-iminium bromide.
AB  - In the cation of the title salt, C16H14Cl2N3S+.Br-, the central thia-zolidine
      ring adopts an envelope conformation. The phenyl ring is disordered over two
      sites with a refined occupancy ratio of 0.541 (9):0.459 (9). In the crystal, C
      H?Br and N-H?Br hydrogen bonds link the components into a three-dimensional
      network with the cations and anions stacked along the b-axis direction. Weak C
      H?pi inter-actions, which only involve the minor disorder component of the ring,
      also contribute to the mol-ecular packing. In addition, there are also inversion
      related Cl?Cl halogen bonds and C-Cl?pi (ring) contacts. A Hirshfeld surface
      analysis was conducted to verify the contributions of the different inter
      molecular inter-actions.

PMID- 30116587
TI  - Crystal structures of Z-Gly-Aib-O-.0.5Ca2+.H2O and Z-Gly-Aib-OH.
AB  - Both deprotonated and neutral achiral title dipeptides assume similar structures
      of two conformations, which are related by a unit-cell inversion centre. Two mol
      ecules of both conformations of the metal-free neutral dipeptide are linked by
      two hydrogen bonds, while two mol-ecules of both conformations of the ionized
      form coordinate a calcium ion in calcium(II) bis-[2-(2-{[(benz-yl-oxy)carbon
      yl]amino}-acetamido)-2-methyl-propano-ate] monohydrate, 0.5Ca2+.C14H17N2O5
      .0.5H2O, which lies on an inversion centre and forms a distorted octa-hedral
      complex with the metal ion. These CaII complexes are connected in the crystal via
      hydrogen bonds in the b- and c-axis directions, whereas in the a-axis direction,
      they stack via apolar contacts. In the metal-free crystal, namely 2-(2-{[(benz
      yloxy)carbon-yl]amino}-acetamido)-2-methyl-propanoic acid, C14H18N2O5, mol-ecules
      are hydrogen bonded in the a- and c-axis directions, and stack in the b-axis
      direction via apolar contacts.

PMID- 30116589
TI  - Crystal structure of tetra-kis-(1,1,1,5,5,5-hexa-fluoro-acetyl
      acetonato)hafnium(IV).
AB  - The crystal structure of the title compound, [Hf(C5HF6O2)4], has been determined.
      The asymmetric unit contains two Hf(hfac)4 mol-ecules (hfac = 1,1,1,5,5,5-hexa
      fluoro-acetyl-acetonate); both are located on general positions and have
      identical structures apart from the disorder involving three CF3 groups in one of
      the two mol-ecules. The mol-ecules of Hf(hfac)4 are arranged in layers that are
      parallel to the ab plane, and the coordination geometry of each hafnium(IV)
      center is a distorted square anti-prism. An inter-esting aspect of the structure
      is that the hfac ligands are arranged so that the Hf(hfac)4 mol-ecules have
      idealized 2 point symmetry, in which two of the hfac groups bridge between the
      two squares. Although all other M(beta-diketonate)4 compounds of Hf (and Zr) also
      have square-anti-prismatic geometries; in almost all of them the ligands are
      arranged so that the mol-ecules have 222 point symmetry (in which none of the
      hfac ligands bridges between the two squares). The factors that favor one
      structure over another are not clear.

PMID- 30116588
TI  - Crystal structure analysis of [5-(4-meth-oxy-phen-yl)-2-methyl-2H-1,2,3-triazol-4
      yl](thio-phen-2-yl)methanone.
AB  - The title compound, C15H13N3O2S, crystallizes in the monoclinic space group P21/n
      and its mol-ecular conformation is stabilized via intra-molecular C-H?O and C-H?N
      contacts. The supra-molecular structure is mainly governed by C-H?N hydrogen
      bonded centrosymmetric dimers, C-H?O and C-H?S hydrogen bonds and S?pi and pi-pi
      stacking inter-actions which, together, lead to the formation of a layered
      crystal packing. The inter-molecular inter-actions were further evaluated through
      the mol-ecular electrostatic potential map and Hirshfeld fingerprint analysis.

PMID- 30116590
TI  - Sustained and targeted episcleral delivery of celecoxib in a rabbit model of
      retinal and choroidal neovascularization.
AB  - Background: To evaluate the efficacy of selective episcleral delivery of
      celecoxib formulated in a sustained-release episcleral exoplant on a model of
      retinal and choroidal neovascularization induced in rabbits by subretinal
      injection of matrigel combined with vascular endothelial growth factor (VEGF) and
      basic fibroblast growth factor (bFGF). Methods: Nine New Zealand white rabbits
      were randomly assigned to three groups (episcleral celecoxib exoplant,
      intravitreal bevacizumab injection and control group). The bFGF was mixed with
      matrigel at a concentration of 10 ug/0.1 mL, and VEGF was mixed with matrigel at
      a concentration of 2 ug/0.1 mL. Animals assigned to celecoxib or intravitreal
      bevacizumab groups were treated within 03 days from matrigel injection.
      Fluorescein angiography (FA) and electroretinography (ERG) were performed 5 days,
      2, 4 and 8 weeks after matrigel injection. Persistence or regression of three
      clinical features (subretinal hyperfluorescence, retinal vascular tortuosity and
      retinal fibrotic spots) was independently evaluated in each study group at all
      follow-up periods. Statistical analysis using Fisher's exact test was performed
      to compare the frequency of findings at each time point between treated groups
      and control. Results: In all study eyes, matrigel induced the appearance of
      subretinal blebs and the development of retinal and subretinal neovascularization
      characterized by progressive and late hyperfluorescence on FA. Persistence of
      subretinal hyperfluorescence was higher in non-treated (control) animals compared
      to celecoxib (p = 0.0238) treated animals. The mean b-wave amplitude ratios of
      ERG recordings did not reveal statistically significant differences between the
      study groups. Control animals retained in average 40% (+/- 7%) of the pre
      treatment recorded b-wave amplitude, compared to 53% (+/- 29%) after bevacizumab
      and 53% (+/- 17%) after celecoxib treatment. Conclusion: In this rabbit model of
      retinal and subretinal neovascularization, episcleral celecoxib delivery was
      demonstrated to significantly inhibit neovascularization. It was also noticed,
      although not statistically significant, an apparent effect of episcleral
      celecoxib on preventing tractional retinal detachment secondary to epiretinal
      fibrovascular proliferation. The transscleral delivery of celecoxib combined with
      sustained-release strategy may have impact in the treatment of retinal and
      choroidal proliferative diseases.

PMID- 30116591
TI  - A novel simulation competition format as an effective instructional tool in post
      graduate medical education.
AB  - Objective: Medical simulation competitions are a growing reality. This study aims
      at exploring if a novel format of simulation competition (SIMCUP) can be an
      effective educational format in post-graduate education. Design: We designed a 2
      day event that included scientific educational lectures, an orientation to the
      competition, familiarization with the simulation lab, and competition time. Day 1
      was devoted to preliminary rounds and was structured using an Objective
      Structured Clinical Examination (OSCE)-like system. On day 2, the first four
      teams advanced to semi-finals and then to finals, which were held using a
      classical SimWars style. Setting and subjects: A total of 14 four-participant
      teams participated in the event over two editions (Ed.1 in 2015 and Ed.2 in
      2016). Interventions: External referees evaluated both technical and non
      technical skills for each simulated scenario. Each participant was also
      administered pre- and post-test questionnaires covering self-perception about the
      confidence in managing simulated clinical cases, educational effectiveness,
      satisfaction with the simulation experience, and previous simulation training.
      Main results: Overall participants found SIMCUP a useful learning experience,
      rating it 10 [9, 10] and 10 [7.75-10] out of 10 for Ed.1 and Ed.2, respectively.
      Participants reported, using a 10-point semantic differential scale ranging from
      "1 - strongly disagree." to "10 - strongly agree," finding both days to be
      educationally effective: day 1 was rated 9 [7-10] and 9 [8-10] as day 2 was rated
      8 [7-10] and 8 [7-10] for Ed. 1 and Ed. 2, respectively.Participants' self
      perception regarding the confidence of managing the specific scenarios
      significantly improved immediately after the event as measured by pre- and post
      questionnaires for all stations and during both editions. Conclusion: This study
      suggests that simulation competition can serve as an effective instructional
      format in residency training.

PMID- 30116593
TI  - Epigenetic biomarkers in cancer.

PMID- 30116594
TI  - Is smoking history the truly best biomarker for immune checkpoint inhibitor
      treatment in advanced non-small cell lung cancer?

PMID- 30116595
TI  - Macrophage repolarisation therapy in colorectal cancer.

PMID- 30116592
TI  - Impact of abiraterone acetate plus prednisone or enzalutamide on fatigue and
      cognition in patients with metastatic castration-resistant prostate cancer:
      initial results from the observational AQUARiUS study.
AB  - Introduction: Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ)
      are commonly prescribed for metastatic castration-resistant prostate cancer
      (mCRPC). Data comparing their effects on patient-reported outcomes (PROs) from
      routine clinical practice are limited. Methods: AQUARiUS (NCT02813408) is an
      ongoing, two-cohort, prospective, observational, non-randomised, multicentre,
      phase IV European study assessing the effects of AAP and ENZ on PROs in 211
      patients with mCRPC over 12 months. Patients receive AAP or ENZ per routine
      clinical practice. Data on cognition, fatigue, pain and health-related quality of
      life are measured using the Functional Assessment of Cancer Therapy-Cognitive
      Function, Brief Fatigue Inventory-Short Form, Brief Pain Inventory-Short Form and
      European Organization for Research and Treatment of Cancer Quality of Life-C30
      questionnaires, respectively. Results: This 3-month analysis was conducted in 105
      patients; 46 received AAP and 59 received ENZ. There were statistically
      significant differences in mean change from baseline favouring AAP over ENZ at
      months 1, 2 and 3 for perceived cognitive impairments and cognitive functioning.
      At each time-point, ENZ-treated patients had a significantly higher risk of
      experiencing clinically meaningful worsening in perceived cognitive impairments
      versus those receiving AAP.Statistically significant differences in mean change
      from baseline favouring AAP over ENZ were seen for usual level of fatigue and
      fatigue interference at months 2 and 3 and for current fatigue and worse level of
      fatigue at month 3. Differences favouring AAP versus ENZ were seen for the
      fatigue scale of the QLQ-C30 questionnaire (months 1 and 3). There was a
      significantly higher risk of clinically meaningful worsening in usual level of
      fatigue with ENZ versus AAP at month 3.No significant differences between cohorts
      were observed for pain (BPI-SF) at any time-point. Conclusion: This analysis
      suggests more favourable outcomes with AAP versus ENZ for cognition and fatigue
      in the first 3 months of treatment initiation for mCRPC. These findings require
      confirmation from future analyses of data from AQUARiUS from a larger number of
      patients with a longer follow-up period.

PMID- 30116596
TI  - Potential challenges of implementing the Community Health Extension Worker
      programme in Uganda.

PMID- 30116597
TI  - Drug-resistant tuberculosis: is India ready for the challenge?

PMID- 30116599
TI  - Making diagnostic tests as essential as medicines.

PMID- 30116598
TI  - Prepared for the 'unexpected'? Lessons from the 2014-2016 Ebola epidemic in West
      Africa on integrating emergent theory designs into outbreak response.

PMID- 30116600
TI  - Correction: Equity in access to non-communicable disease medicines: a cross
      sectional study in Kenya.
AB  - [This corrects the article DOI: 10.1136/bmjgh-2018-000828.].

PMID- 30116601
TI  - One century after 1918 flu pandemic, an ultimate solution remains pending...

PMID- 30116602
TI  - Development and application of bioluminescence imaging for the influenza A virus.
AB  - Influenza A viruses (IAVs) cause seasonal epidemics and intermittent pandemics
      which threaten human health. Conventional assays cannot meet the demands for
      rapid and sensitive detection of viral spread and pathogenesis in real time
      cannot be used for high-throughput screens of novel antivirals. Bioluminescence
      imaging (BLI) has emerged as a powerful tool in the study of infectious diseases
      in animal models. The advent of influenza reverse genetics has enabled the
      incorporation of bioluminescent reporter proteins into replication-competent
      IAVs. This review briefly describes the current development and applications of
      bioluminescence in the study of viral infections and antiviral therapeutics for
      IAVs. BLI is expected to substantially accelerate the basic and applied research
      of IAV both in vitro and in vivo.

PMID- 30116603
TI  - Atypical antibody responses to influenza.
AB  - Influenza viruses undergo rapid antigenic evolution and reassortment, resulting
      in annual epidemics and the occasional pandemics. Exposure to influenza virus
      hemagglutinin (HA) and neuraminidase (NA) antigen, either through vaccination or
      infection, induces an antibody response able to recognize only the homologous
      antigenic subtype. However, atypical antibody responses recognizing non
      homologous influenza subtypes have been reported during infection and
      vaccination. Here, we review the incidence of these phenomena in published
      literature and discuss the potential mechanisms underlying them.

PMID- 30116605
TI  - Current understanding of middle east respiratory syndrome coronavirus infection
      in human and animal models.
AB  - Middle East respiratory syndrome (MERS) is a highly lethal respiratory disease
      caused by a novel betacoronavirus (MERS coronavirus, MERS-CoV). Since its first
      emergence in 2012, multiple transmission events of MERS-CoV (dromedary to human
      and human to human) have been reported, indicating that MERS-CoV has the
      potential to cause widespread outbreak. However, the epidemiology of MERS as well
      as immune responses against the virus in animal models and patients are still not
      well understood, hindering the vaccine and therapeutic developments. In this
      review, we summarize recent genetic and epidemic findings of MERS-CoV and the
      progress in animal model development, immune response studies in both animals and
      humans. At last, we discussed the breakthrough on vaccine and therapeutic
      development which are important against potential future MERS outbreak.

PMID- 30116606
TI  - The tree shrew as a model for infectious diseases research.
AB  - Despite major advances in medicine, infectious diseases still pose a significant
      threat to humanity. Mammalian models of disease have proved extremely useful in
      adding to the understanding of infectious diseases and the development of
      prophylactic and/or therapeutic interventions. Arguably the most important
      considerations of any animal model are (I) the similarity of the model to humans
      with respect to anatomy, physiology, immunology and disease progression, and (II)
      the expense of conducting experiments using the model organism. Often the choice
      of a model represents a compromise between these factors. Here we review the
      Northern Tree shrew (Tupaia belangeri), or tupaia, as a useful model for the
      study of infectious diseases. Tupaias are non-human primates similar in size to
      squirrels that are indigenous to Asia. Their genome has been sequenced and,
      overall, shows relatively high similarity to humans. There is also a close
      homology of many aspects of tupaia biology with human biology. Importantly, from
      an infectious diseases viewpoint, tupaias are susceptible to infection with
      unadapted human pathogens and manifest clinical signs akin to human infections.
      Overall, the relatively small size of the tupaia, their homology to humans and
      their susceptibility to human pathogens make them a useful model for the study of
      infectious diseases.

PMID- 30116604
TI  - Re-understanding anti-influenza strategy: attach equal importance to antiviral
      and anti-inflammatory therapies.
AB  - The direct replication of influenza virus is not the only cause of harm to human
      health; influenza infection leading to a hyper-inflammatory immune response can
      also result in serious conditions. So, the treatment strategy for influenza needs
      to keep balance between antivirus and anti-inflammation. Herein, we review the
      treatment strategies of anti-influenza drugs and traditional Chinese medicines.

PMID- 30116608
TI  - Ventilation control for airborne transmission of human exhaled bio-aerosols in
      buildings.
AB  - The emergence of respiratory diseases, i.e., severe acute respiratory syndrome
      (SARS) epidemic in 2003, H1N1 influenza epidemic in 2011 and Middle East
      respiratory syndrome (MERS) outbreak, reiterated the significance of ventilation
      in buildings. The role of ventilation in removing exhaled airborne bio-aerosols
      and preventing cross infections has been multidisciplinary extensively studied
      after the SARS outbreak in 2003. The characteristics of droplet-borne, short
      range airborne and long-range airborne transmission of infectious diseases were
      identified. Increasing ventilation rate can effectively reduce the risk of long
      range airborne transmission, while it may be of little useful in preventing the
      droplet-borne transmission. To maintain the airflow direction from clean cubicles
      to dirty cubicles is an effective way to prevent the cross infection between
      cubicles, which is widely used in hospital isolation rooms. Field measurements
      showed that wrong air flow direction was due to poor construction quality or
      maintenance. The impacts of different airflow patterns on removing large droplets
      and fine droplet nuclei were discussed. Some new concepts in general ventilation
      systems and local personalized equipment were also introduced. This review
      updates current knowledge of the airborne transmission of pathogens and the
      improvement of ventilation efficiency concerning the infection prevention.

PMID- 30116609
TI  - A case report on parainfluenza virus type 4a infection in a 1-year-old boy with
      biphasic fever.
AB  - A 1-year-old boy was infected with parainfluenza virus type 4a (PIV4a) during an
      influenza epidemic in January 2016. His body temperature was 38.2  degrees C on
      day 1 of the illness followed by an intermittent phase of 36.5  degrees C on days
      2 and 3, and it rose again on day 3 and peaked at 39.6  degrees C on day 4, of
      which the fever pattern was reminiscent of an influenza case with biphasic fever.
      However, results of rapid influenza virus (IFV) antigen tests performed at the
      first clinical visit and during the second fever phase on day 4 were both
      negative. The PIV4a was isolated from all the nasal aspirate specimens on days 1,
      4, and 7. Other common respiratory viruses were negative in all the specimens in
      the viral isolation trials using the multiplex cell culture system and RT-PCR
      tests. The fever disappeared within 5 days after the onset without any antibiotic
      treatment, which strongly suggested the PIV4a as the causative agent of the
      patient's illness. On the basis of the incubation period required for the
      appearance of the cytopathic effect (CPE) in the infected cells, from specimen
      inoculation to the cells, the viral load in the nasal cavity was speculated to be
      greatest on day 4. His cough started on day 1 and persisted until day 9, and the
      viral isolation indicated that the shedding of the active virus continued with
      the coughing even after the termination of fever.

PMID- 30116607
TI  - Vaccine development for human mastadenovirus.
AB  - Human mastadenovirus (HAdVs) can cause a broad spectrum of diseases in both
      children and adults, including acute respiratory infection, gastroenteritis,
      epidemic keratoconjunctivitis. Populations susceptible to adenovirus infection
      include children, immunocompromised patients and military recruits. To date,
      seven species (A-G) including more than 79 genotypes have been characterized, of
      which HAdV-B3, B4, B7 and the recently reemerged types 14 and 55 often lead to
      severe pneumonia. The live oral enteric-coated adenovirus type 4 and 7 vaccine,
      which was approved for use in US military personnel of 17 through 50 years of
      age, had been shown to be safe and highly effective in numerous clinical trials
      and by ongoing surveillance of febrile respiratory illness. However, there is
      currently no vaccine approved for general use in children and adults in any part
      of the world. This review article will summarize the epidemiological data
      available for adenovirus and the effectiveness of the adenovirus vaccine in the
      US military. It will also provide a brief overview of innovative vaccine
      strategies, animal models for vaccine evaluation, and issues regarding vaccine
      production.

PMID- 30116610
TI  - Hypertension and Cerebral Microangiopathy (Cerebral Small Vessel Disease):
      Genetic and Epigenetic Aspects of Their Relationship.
AB  - Hypertension (HT) and its cerebral complications are extremely vexing medical and
      social problems. Despite the obvious association between hypertension and the
      clinical and neuroimaging features of cerebral microangiopathy (CMA) (also known
      as cerebral small vessel disease), the causal links between them remain
      ambiguous. Besides, antihypertensive therapy as the only way to manage these
      patients does not always prevent brain damage. Knowledge about the key factors
      and mechanisms involved in HT and CMA development is important for predicting the
      risk of cerebral complications and developing new approaches to their prevention
      and treatment. At present, genome-wide association studies and other approaches
      are used to investigate the common hereditary mechanisms of HT and CMA
      development, which will explain a large number of CMA cases not associated with
      hypertension, lack of a correlation between HT severity and the degree of
      cerebral injury, and failure of antihypertensive therapy to prevent CMA
      progression. Epigenetic markers likely play a modulating role in the development
      of these diseases.

PMID- 30116612
TI  - Organism-Level Tumor Models in Zebrafish Danio rerio.
AB  - Development and implementation of adequate organism-level models is one of the
      key elements in biomedical research that focuses on experimental oncology. Over
      the last decade, studies using Zebrafish (Danio rerio) have gained in popularity
      in this area of research. This review describes the various approaches that have
      been used in developing highly effective models for oncological (clinical term,
      better cancer or tumor) studies based on D. rerio. Priority is given to
      transplantation models of cancer and their application to optically transparent
      D. rerio lines, including clonal ones, and utilization tumors of various origins
      bearing fluorescent labels. The combination of tumor transplantation at organism
      level models in transparent clonal D. rerio lines with fluorescent microscopy,
      FACS-fractionation of tumor cell subsets, and transcription analysis can result
      in one of the most promising research approaches in providing new information on
      tumor formation and growth.

PMID- 30116611
TI  - Molecular Approaches to Safe and Controlled Engineered T-cell Therapy.
AB  - Chimeric antigen receptor-modified T-cell therapy (CAR-T therapy) is one of the
      fastest developing areas of immuno-oncology. Over the past decade, it has
      revolutionized the cell therapy modality and expedited its pace of development,
      from optimization of the structure of chimeric antigen receptors and animal model
      experiments to successful clinical application. The initial designs of the CAR
      configuration focused on increasing T-cell activation, cytotoxicity, and
      persistence. However, the first attempts to treat patients with CAR T cells have
      demonstrated the need for increased safety and controlled activation of
      genetically modified T cells. Herein, we summarize the different molecular
      approaches to engineering chimeric antigen receptors for reducing the potential
      clinical risks of T-cell therapy.

PMID- 30116613
TI  - The Development and Study of Recombinant Immunoglobulin A to Hemagglutinins of
      the Influenza Virus.
AB  - We obtained recombinant variants of human antibody FI6 broadly specific to
      hemagglutinins of the influenza A virus. On the basis of a bi-promoter (CMV, hEF1
      HTLV) vector, we developed genetic constructs for the expression of the heavy and
      light chains of the immunoglobulins of IgA1-, IgA2m1-, and IgG-isotypes.
      Following transfection and selection, stable Chinese hamster ovary (CHO) cell
      lines were produced. The antibodies of IgA1-, IgA2m1-, and IgG-isotypes were
      purified from culture media. We performed an immunochemical characterization and
      studied their interactions with influenza A strains of the H1N1- and H3N2
      subtypes. It was shown that recombinant FI6 variants of the IgA-isotype retain
      the properties of the parental IgG antibody to demonstrate specificity to all the
      strains tested. The strongest binding was observed for the H1N1 subtype, which
      belongs to hemagglutinins of phylogenetic group I.

PMID- 30116614
TI  - Cognitive Tagging of Neurons: CREMediated Genetic Labeling and Characterization
      of the Cells Involved in Learning and Memory.
AB  - In this study, we describe use of Cre-mediated recombination to obtain a
      permanent genetic labeling of the brain neuronal networks activated during a new
      experience in animals. This method utilizes bitransgenic Fos-Cre-eGFP mice in
      which a green fluorescent protein is expressed upon tamoxifen-induced Cre
      recombination only in the cells where immediate early gene c-fos expression takes
      place due to the new experience. We used the classical fear conditioning model to
      show that ex vivo microscopy of the eGFP protein in Fos-Cre-eGFP mice enables
      mapping of the neurons of the various brain regions that undergo Cre
      recombination during acquisition of a new experience. We exposed the animals to
      the new environment in brief sessions and demonstrated that double
      immunohistochemical staining enables a characterization of the types of
      neocortical and hippocampal neurons that undergo experience-dependent Cre
      recombination. Notably, Fos-Cre-eGFP labeled cells appeared to belong to
      excitatory pyramidal neurons rather than to various types of inhibitory neurons.
      We also showed that a combination of genetic Cre-eGFP labeling with
      immunohistochemical staining of the endogenous c-Fos protein allows one to
      identify and compare the neuronal populations that are activated during two
      different episodes of new experiences in the same animal. This new approach can
      be used in a wide spectrum of tasks that require imaging and a comparative
      analysis of cognitive neuronal networks.

PMID- 30116615
TI  - Characterization of the T-cell Repertoire after Autologous HSCT in Patients with
      Ankylosing Spondylitis.
AB  - Autologous hematopoietic stem cell transplantation (HSCT), a safer type of HSCT
      than allogeneic HSCT, is a promising therapy for patients with severe autoimmune
      diseases (ADs). Despite the long history of medical practice, structural changes
      in the adaptive immune system as a result of autologous HSCT in patients with
      various types of ADs remain poorly understood. In this study, we used high
      throughput sequencing to investigate the structural changes in the peripheral
      blood T-cell repertoire in adult patients with ankylosing spondylitis (AS) during
      two years after autologous HSCT. The implementation of unique molecular
      identifiers allowed us to substantially reduce the impact of the biases occurring
      during the preparation of libraries, to carry out a comparative analysis of the
      various properties of the T-cell repertoire between different time points, and to
      track the dynamics of both distinct T-cell clonotypes and T-cell subpopulations.
      In the first year of the reconstitution, clonal diversity of the T-cell
      repertoire remained lower than the initial one in both patients. During the
      second year after HSCT, clonal diversity continued to increase and reached a
      normal value in one of the patients. The increase in the diversity was associated
      with the emergence of a large number of low-frequency clonotypes, which were not
      identified before HSCT. Efficiency of clonotypes detection after HSCT was
      dependent on their abundance in the initial repertoire. Almost all of the 100
      most abundant clonotypes observed before HSCT were detected 2 years after
      transplantation and remained highly abundant irrespective of their CD4+ or CD8+
      phenotype. A total of up to 25% of peripheral blood T cells 2 years after HSCT
      were represented by clonotypes from the initial repertoire.

PMID- 30116616
TI  - 1-(4-Phenoxybenzyl) 5-Aminouracil Derivatives and Their Analogues - Novel
      Inhibitors of Human Adenovirus Replication.
AB  - Adenovirus infections are characterized by widespread distribution. The lack of
      causal therapy, which is effective in treating this group of diseases, explains
      the need for new therapeutic drugs. Notably, anti-adenoviral activity of [4
      (phenoxy)benzyl]-5-(phenylamino)-6-azauracil, 1-[4-(phenoxy)benzyl]-5
      (morpholino) uracil, 1-[4-(4-chlorophenoxy)benzyl]-5-(morpholino) uracil, and 1
      [4-(4-fluorophenoxy)-benzyl]-5-(morpholino) uracil was observed.

PMID- 30116617
TI  - Reversible Cyclic Thermal Inactivation of Oligopeptidase B from Serratia
      proteamaculans.
AB  - A unique property was found for oligopeptidase B from Serratia proteamaculans
      (PSP) as well as its mutants: they can undergo reversible thermal inactivation at
      37 degrees C, with activity being restored or even increased with respect to the
      initial one upon subsequent cooling. The process can be repeated several times,
      with the same results achieved (up to 5 cycles). This effect can be explained by
      a shift in the equilibrium between the inactive open form of the enzyme and the
      active closed one upon variation of the incubation temperature.

PMID- 30116619
TI  - Phylogenetic Analysis and Molecular Typing of Trichothecene-Producing Fusarium
      Fungi from Russian Collections.
AB  - We performed a three-locus phylogenetic analysis of Fusarium strains presumably
      capable of trichothecene production, which were deposited in the Russian national
      collections. The intra- and interspecific polymorphism of partial sequences of
      the translation elongation factor 1 alpha (TEF1alpha) gene and two genes from the
      trichothecene cluster TRI5 and TRI14 was studied. A study of 60 strains of
      different origins using DNA markers confirmed, and in the case for several
      strains, clarified their taxonomic characteristics. As a result, a strain of F.
      commune (F-900) was identified in Russia for the first time. Furthermore, the
      strain F-846 proved to be phylogenetically distinct from any of the known
      Fusarium species. F. equiseti strains from Northwest Russia were found to belong
      to the North European group (I), whereas a strain from the North Caucasus - to
      the South European one (II). Partial TRI14 sequences from 9 out of 12 species
      were determined for the first time. Their comparative analysis demonstrated a
      relatively high level of intraspecific variability in F. graminearum and F.
      sporotrichioides, but no correlation between the sequence polymorphism and the
      geographic origin of the strains or their chemotype was found. Specific
      chemotypes of trichothecene B producers were characterized using two primer sets.
      The chemotyping results were verified by HPLC.

PMID- 30116620
TI  - ATP Reduces the Entry of Calcium Ions into the Nerve Ending by Blocking L-type
      Calcium Channels.
AB  - At neuromuscular junctions, ATP inhibits both the evoked and spontaneous
      acetylcholine release and inward calcium current operating via presynaptic P2Y
      receptors. It was shown in the experiments with the frog neuromuscular synapse
      using specific calcium-sensitive dye Oregon Green Bapta 1 that exogenous ATP
      reduces the amplitude of calcium transient, which reflects the changes in the
      entry of calcium ions in response to the nerve pulse. The depressing effect of
      ATP on the transient was prevented by suramin, the blocker of P2 receptors.
      Nitrendipine, a specific blocker of L-type calcium channels, per se decreased the
      calcium transient amplitude and significantly attenuated the effect of ATP on the
      calcium signal. Contrariwise, the preliminary application of ATP to the
      neuromuscular junction completely eliminated the depressing effect of
      nitrendipine on the calcium response. The obtained data suggest that an essential
      component in the inhibitory action of ATP on the calcium transient amplitude is
      provided by reduction of the entry of calcium ions into a frog nerve ending via L
      type voltage-gated calcium channels.

PMID- 30116618
TI  - Soluble Guanylate Cyclase As the Key Enzyme in the Modulating Effect of NO on
      Metabotropic Glutamate Receptors.
AB  - The synaptic plasticity of the afferent synapse of the vestibular apparatus is
      defined by the dynamic interaction of ionotropic and metabotropic glutamate
      receptors and the modulators of synaptic transmission. It was shown that nitric
      oxide modulates iGluR responses. In this paper, the effect of NO on the function
      of the afferent synapse mGluR was investigated. Inhibitor of nitric oxide
      synthase lowered the level of background activity but increased the amplitude of
      the responses of groups I and II mGluR agonist ACPD. Donor NO SNAP increased the
      level of background activity. Short-term perfusion of the synaptic region with
      low concentrations of SNAP led to a decrease in the amplitude of the answers of
      mGluR agonists ACPD and DHPG. The inhibitory effect of the NO donor was
      eliminated under blockade of soluble guanylate cyclase with a specific inhibitor
      ODQ. A prolonged application of NO did not cause a statistically significant
      change in the amplitude of the ACPD response. However, SNAP at concentrations of
      10 and 100 MUM increased the amplitude of the mGluR agonist responses 30 and 15
      minutes, respectively, after termination of the NO donor exposure. The obtained
      data show the multidirectional effect of NO on the function of mGluR and testify
      to the existence of a complex modulating mechanism of the afferent flow from
      vestibular organs to the central nervous system.

PMID- 30116621
TI  - Role of the Scaffold Protein MIM in the Actin-Dependent Regulation of Epithelial
      Sodium Channels (ENaC).
AB  - Epithelial Sodium Channels (ENaCs) are expressed in different organs and tissues,
      particularly in the cortical collecting duct (CCD) in the kidney, where they fine
      tune sodium reabsorption. Dynamic rearrangements of the cytoskeleton are one of
      the common mechanisms of ENaC activity regulation. In our previous studies, we
      showed that the actin-binding proteins cortactin and Arp2/3 complex are involved
      in the cytoskeleton-dependent regulation of ENaC and that their cooperative work
      decreases a channel's probability of remaining open; however, the specific
      mechanism of interaction between actin-binding proteins and ENaC is unclear. In
      this study, we propose a new component for the protein machinery involved in the
      regulation of ENaC, the missing-in-metastasis (MIM) protein. The MIM protein
      contains an IMD domain (for interaction with PIP2 -rich plasma membrane regions
      and Rac GTPases; this domain also possesses F-actin bundling activity), a PRD
      domain (for interaction with cortactin), and a WH2 domain (interaction with G
      actin). The patch-clamp electrophysiological technique in whole-cell
      configuration was used to test the involvement of MIM in the actin-dependent
      regulation of ENaC. Co-transfection of ENaC subunits with the wild-type MIM
      protein (or its mutant forms) caused a significant reduction in ENaC-mediated
      integral ion currents. The analysis of the F-actin structure after the
      transfection of MIM plasmids showed the important role played by the domains PRD
      and WH2 of the MIM protein in cytoskeletal rearrangements. These results suggest
      that the MIM protein may be a part of the complex of actin-binding proteins which
      is responsible for the actin-dependent regulation of ENaC in the CCD.

PMID- 30116623
TI  - Choroid and Retinal Nerve Fiber Layer Thickness in Patients with Chronic
      Obstructive Pulmonary Disease Exacerbation.
AB  - Purpose: We aimed at measuring the choroid and retinal nerve fiber layer
      thickness with optic coherence tomography (OCT) in patients diagnosed with
      chronic obstructive pulmonary disease (COPD). Methods: A total of 60 patients
      with COPD and 23 healthy controls were evaluated in the scope of this
      prospective, observational study. COPD patients were divided into two groups as
      those that were stable and those with an exacerbation based on the Global
      Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Subfoveal
      choroid thickness (SFCT) of the patients and the control group was compared by
      measuring the choroid thickness at points 1000 um nasal and temporal to the fovea
      and the mean retinal nerve fiber layer (RNFL) thickness. Results: The subfoveal
      choroid thickness of the COPD patients in both the exacerbation and stable groups
      was found to be statistically significantly thinner than the control group
      (p=0.047 and p=0.046, resp.). No statistically significant difference was found
      between the subfoveal choroid thickness of the patients that were stable and
      those that had an exacerbation (p=0.813). No statistically significant difference
      was found between the mean RNFL, 1000 um nasal, or 1000 um temporal choroid
      thicknesses of the COPD patients and the control group (p=0.263, p=0.455, and
      p=0.611, resp.). Conclusion: Decreased subfoveal choroid thickness was found in
      the COPD patients both during an exacerbation and in the stable period, when
      compared to the control group. The mean RNFL thickness was similar in the
      exacerbation and stable period of the stable COPD patients when compared to the
      control group. This suggests that ocular findings might be important in terms of
      COPD morbidity. This trial is registered with www.chictr.org.cn/enIndex.aspx.

PMID- 30116622
TI  - Five-Year Incidence and Progression of Diabetic Retinopathy in Patients with Type
      II Diabetes in a Tertiary Care Center in Lebanon.
AB  - Objective: To estimate the 5-year incidence of progression rate and regression
      rate and risk factors for diabetic retinopathy (DR) in a cohort of Lebanese
      patients with type II diabetes. Methods: We followed a cohort of 462 Lebanese
      patients with type II diabetes for over 5 years at the American University of
      Beirut Medical Center. Patients underwent yearly complete ophthalmic evaluation
      and fundus photographs and were assessed for the incidence, stage, and evolution
      of DR using modified Airlie House classification. Results: Among the 462
      patients, 281 had no DR at baseline. The 5-year cumulative incidence of any DR
      was 10% (95% CI: 6-13), and only baseline microalbuminuria correlated with the
      development of DR (OR = 10.53, 95% CI: 4.39-25.23, p < 0.0001). Among the 181
      patients with baseline DR, the worsening and regression rates of DR were 31.5%
      (95% CI: 25-38) and 9% (95% CI: 5-13), respectively. Microalbuminuria also
      approached statistical significance as a risk factor for DR worsening (OR = 1.89,
      95% CI: 0.97-3.70, p = 0.06). Conclusion: The 5-year incidence of DR in this
      hospital-based cohort is relatively low. Microalbuminuria was independently
      associated with the incidence and progression of the disease. We recommend to
      screen patients with type II diabetes for microalbuminuria as prognostic for the
      development and worsening of DR.

PMID- 30116624
TI  - Assessment of Ocular Surface Damage during the Course of Type 2 Diabetes
      Mellitus.
AB  - Purpose: To investigate the impact of disease duration on the ocular surface
      during the course of type 2 diabetes mellitus compared with nondiabetic controls.
      Methods: One hundred twenty diabetic patients were divided into three groups
      according to disease duration: less than 5 years, 5-10 years, and over 10 years.
      All eyes were imaged using a corneal topographer (Oculus Keratograph 5M). Tear
      film measurements and meibography were also recorded. Meibomian gland changes
      were scored from 0 to 6 (meiboscore). Results: The noninvasive breakup time first
      (NIKBUT-1st) and noninvasive breakup time average (NIKBUT-avg) were significantly
      shorter in the over 10 years diabetic group compared with the control group
      (P=0.0056  and  P=0.010, resp.). Tear meniscus height (TMH) was significantly
      lower in the over 10 years diabetic group compared with the control group
      (P=0.0016) and the 5 years group (P=0.0061). We also found that more patients in
      the over 10 years diabetic group showed bulbar and limbal hyperemia compared with
      the control group (bulbar hyperemia: P=0.049; limbal hyperemia: P=0.026). The
      meiboscore in the over 10 years diabetic group was significantly higher compared
      with the other three groups (P < 0.05). Bulbar hyperemia showed a significant
      negative correlation with NIKBUT-1st in the over 10 years diabetic group (r=-0.35
      and  P < 0.05). Conclusion: Ocular surface damage in long-term type 2 diabetes
      is more severe than that in patients with shorter disease duration.

PMID- 30116625
TI  - Outcomes of Wound Dehiscence after Penetrating Keratoplasty and Lamellar
      Keratoplasty.
AB  - Objective: To investigate the incidence, causes, occurrence time, and range of
      wound and outcomes of wound dehiscence in patients treated by penetrating
      keratoplasty (PK) or lamellar keratoplasty (LK). Methods: We retrospectively
      reviewed medical records of keratoplasty in Shandong Eye Hospital from January
      2006 to June 2017. Thirty-one eyes of 30 patients had sustained wound dehiscence
      (WD) after surgical treatment. The surgical type, causes, occurrence time, extent
      of the wound, treatment, and outcomes were recorded. Results: The study
      population consisted of 26 men and 4 women. The mean age at the occurrence of WD
      was 44.6 years old (range: 12-78 years), and the mean time from keratoplasty to
      WD was 45.9 months (range: 1-204 months). WD occurred in 23 eyes (23/1385, 1.66%)
      after PK and 8 eyes (8/1632, 0.49%) after LK (p < 0.05). Twenty-seven eyes
      (27/31, 87.0%) had trauma-induced dehiscence. The mean range of dehiscence was
      5.5 o'clock. The vision ranged from 20/50 to light perception after wound suture.
      The eyes receiving LK had fewer serious complications than PK. Conclusions:
      Compared with LK, PK seems to be more prone to result in wound dehiscence. The WD
      after LK may be less severe. The visual acuity after treatment of WD can be worse
      in the eyes with PK than LK.

PMID- 30116626
TI  - The Effect of NSAID Pretreatment on Aqueous Humor Prostaglandin E2 Concentration
      in Eyes Undergoing Femtosecond Laser-Assisted Capsulotomy.
AB  - Purpose: To assess aqueous humor concentration of prostaglandin E2 (PGE2) after
      capsulotomy creation using a femtosecond laser (FLAC) in patients pretreated with
      short-term topical ketorolac versus patients without pretreatment. Methods: This
      prospective study comprised consecutive patients scheduled to undergo cataract
      surgery using a femtosecond laser platform to perform only capsulotomies. An
      identical protocol for preoperative mydriasis was used for all the eyes included
      in the study, while aqueous humor was extracted from the anterior chamber of all
      patients immediately after the initial side port incision. ELISA was performed to
      quantify aqueous humor PGE2. The patients were divided into 2 groups; in group 1,
      the patients received short-term topical ketorolac preoperatively, while the
      patients in group 2 did not receive NSAID pretreatment. Results: Twenty eyes of
      20 patients were included in the study (10 eyes in each group). Mean
      concentration of aqueous humor PGE2 after FLAC was 392.16 +/- 162.00 pg/ml and
      622.63 +/- 331.84 pg/ml for groups 1 and 2, respectively. A statistically
      significant difference in aqueous humor PGE2 concentration between the two groups
      (p < 0.05) was demonstrated, with the eyes that received ketorolac pretreatment
      demonstrating a lower concentration of PGE2. Conclusion: Short-term topical use
      of ketorolac prior to FLAC seems to prevent excessive release of PGE2 in the
      anterior chamber of the eyes that received NSAID pretreatment when compared to
      the eyes that did not receive NSAIDs preoperatively.

PMID- 30116627
TI  - Transpalpebral Electrical Stimulation as a Novel Therapeutic Approach to Decrease
      Intraocular Pressure for Open-Angle Glaucoma: A Pilot Study.
AB  - Purpose: To determine the effect on intraocular pressure of transpalpebral
      specific exogenous voltages in a cohort of open-angle glaucoma patients. Methods:
      This is a prospective, comparative, and experimental pilot study. The electrical
      stimuli applied consisted of 10 Hz, biphasic, nonrectangular current pulses (100
      MUA) delivered from an isolated constant current stimulator. At intake, baseline
      IOP measurements were obtained from each eye. The measurement was repeated before
      and after microstimulation until the end of the treatment. Results: Seventy-eight
      eyes of 46 patients diagnosed with POAG were studied: 58 eyes with maximum
      tolerated medical treatment and 20 eyes without treatment (naive). The mean
      baseline IOP on the treated POAG group was 19.25 mmHg +/- 4.71. Baseline IOP on
      the naive group was 20.38 mmHg +/- 3.28. At the four-month follow-up visit, the
      mean IOP value on the treatment group was 14.41 mmHg +/- 2.06 (P < 0.0001). The
      obtained mean IOP measurement on the treatment-naive group was 15.29 mmHg +/-
      2.28 (P < 0.0001). Conclusions: The hypotensive response obtained using
      transpalpebral electrical stimulation on POAG patients, both on treatment-naive
      patients and on patients receiving maximum tolerable treatment, was statistically
      significant when comparing basal IOP measurements to those obtained at the four
      month follow-up visit.

PMID- 30116628
TI  - Peripheral Cone Dystrophy: Expanded Clinical Spectrum, Multimodal and Ultrawide
      Field Imaging, and Genomic Analysis.
AB  - Purpose: To present new clinical features, multimodal and ultrawide-field imaging
      characteristics of peripheral cone dystrophy (PCD), and results of laboratory and
      genetic investigation to decipher the etiology. Methods: Retrospective
      observational case-series. Results: Three patients with PCD presented with
      bilateral paracentral scotomas and a mean visual acuity of 20/25. All exhibited
      confluent macular hyperautofluorescence with a central bull's eye lesion.
      Spectral-domain optical coherence tomography revealed loss of outer retinal
      elements, particularly the inner segment ellipsoid band and external limiting
      membrane, within the area of macular hyperautofluorescence. This area
      corresponded with a lightened fundus appearance and variable retinal pigment
      epithelium (RPE) abnormalities. Full field and multifocal electroretinography
      distinguished PCD from other photoreceptor dystrophies. Ultrawide-field imaging
      revealed irregular peripheral retinal lesions in a distribution greater nasally
      than temporally and not contiguous with the macular lesion. Functional and
      anatomic testing remained stable over a mean follow-up of 3 years. Laboratory
      investigation for causes of uveitis was negative. Whole exome sequencing
      identified rare variants in genes associated with macular or cone dystrophy or
      degeneration. Conclusions: In contrast to the original description, the
      funduscopic and fluorescein angiographic appearance of PCD is abnormal, although
      the defects are subtle. Peripheral lesions may be observed in some patients.
      Bilateral, symmetric, macular hyperautofluorescence associated with outer retinal
      atrophy that spares the fovea is a characteristic of PCD. Pathogenic variants in
      the same gene were not shared across the cohort, suggesting genetic
      heterogeneity. Further evaluation is warranted.

PMID- 30116629
TI  - The Role of Dll4/Notch Signaling in Normal and Pathological Ocular Angiogenesis:
      Dll4 Controls Blood Vessel Sprouting and Vessel Remodeling in Normal and
      Pathological Conditions.
AB  - Background: Retina is the highest oxygen-demanding and vascularized tissue in the
      body. Retinal development and function require proper vascularization and blood
      vessel function and integrity. Dll4 is most prominently expressed in the
      endothelium of angiogenic blood vessels and in quiescent arteries and capillaries
      in all tissues and organs of the mammalian species, and it is the key regulator
      of blood vessel sprouting. Results: Dll4 is a transmembrane protein that acts as
      a ligand for Notch receptors 1 and 4. Genetic deletion of Dll4 causes severe
      abnormalities in embryonic and postnatal vascular development. Deletion of even a
      single Dll4 allele results in almost complete embryonic lethality due to severe
      vascular abnormalities, the phenomenon called haploinsufficiency indicating the
      critical role of Dll4/Notch in vascular development. Dll4/Notch pathway
      interplays at multiple levels with other signaling pathways including VEGF,
      Wnt/Fzd, and genes controlling vascular toning. Multiple studies of the effects
      of Dll4 inhibition were performed in the developing retina to elucidate the key
      functions of Dll4 in normal and pathological angiogenesis. Several genetic
      approaches and therapeutic molecules were tested to evaluate the biological and
      therapeutic effects of acute and prolonged Dll4 inhibition in the eye and
      oncology. Conclusions: All current studies demonstrated that Dll4 controls blood
      vessel sprouting, growth, and remodeling in normal and pathological conditions as
      well as arterial-venous differentiation. Genetic and therapeutic Dll4 modulation
      studies show that Dll4 inhibition can promote blood vessel sprouting and might be
      useful to stimulate vessel growth in the ischemic retina and Dll4 is the key
      modulator of the postangiogenic vascular remodeling that ultimately defines
      vascular patterning.

PMID- 30116630
TI  - Lanosterol Synthase Pathway Alleviates Lens Opacity in Age-Related Cortical
      Cataract.
AB  - Purpose: Lanosterol synthase (LSS) abnormity contributes to lens opacity in rats,
      mice, dogs, and human congenital cataract development. This study examined
      whether LSS pathway has a role in different subtypes of age-related cataract
      (ARC). Methods: A total of 390 patients with ARC and 88 age-matched non-ARC
      patients were enrolled in this study. LSS expression was analyzed by western blot
      and enzyme-linked immunosorbent assay (ELISA). To further examine the function of
      LSS, we used U18666A, an LSS inhibitor in rat lens culture system. Results: In
      lens epithelial cells (LECs), LSS expression in LECs increased with opaque degree
      C II, while it decreased with opaque degree C IV and C V. While in the cortex of
      age-related cortical cataract (ARCC), LSS expression was negatively related to
      opaque degree, while lanosterol level was positively correlated to opaque degree.
      No obvious change in both LSS and lanosterol level was found in either LECs or
      the cortex of age-related nuclear cataract (ARNC) and age-related posterior
      subcapsular cataract (ARPSC). In vitro, inhibiting LSS activity induced rat lens
      opacity and lanosterol effectively delayed the occurrence of lens opacity.
      Conclusions: This study indicated that LSS and lanosterol were localized in the
      lens of human ARC, including ARCC, ARNC, and ARPSC. LSS and lanosterol level are
      only correlated with opaque degree of ARCC. Furthermore, activated LSS pathway in
      lens is protective for lens transparency in cortical cataract.

PMID- 30116631
TI  - Inhibition of Proteasome Activity Upregulates IL-6 Expression in RPE Cells
      through the Activation of P38 MAPKs.
AB  - Purpose: As far as we know, during the development of age-related macular
      degeneration (AMD), the activity of proteasome in retinal pigment epithelium
      cells (RPE) gradually decreases. And a lot of research has shown that age-related
      macular degeneration is closely related to inflammation and autoimmune. Moreover,
      there are many cytokines (CKs) involved in the course of inflammation. In this
      study, we are going to investigate how the decrease of proteasome activity
      affects the production of interleukin-6 (IL-6) in human retinal pigment
      epithelium cells (ARPE-19). Methods: Cultured ARPE-19 was treated with or without
      MG132, a proteasome inhibitor, and the levels of IL-6 mRNA (messenger ribonucleic
      acid) in RPE at 1 h, 4 h, 8 h, and IL-6 protein in the culture medium at 2 h, 4
      h, 6 h, 8 h, 10 h, and 12 h were measured by real-time polymerase chain reaction
      (real-time PCR) and enzyme-linked immunosorbent assay (ELISA). The protein levels
      of MCP-1 (monocyte chemoattractant protein-1) in the culture medium at 2 h, 4 h,
      6 h, 8 h, 10 h, and 12 h were also measured by ELISA. Then we tested which of
      cell signal pathways regulating the production of IL-6 were activated when we
      added MG132 into the medium by Western blot and electrophoretic mobility shift
      assays (EMSA). After that, we put the inhibitors of these activated cell signal
      pathways into the medium individually to see which inhibitor can counteract the
      effect of upregulating the levels of IL-6 in the culture medium of RPE. Results:
      MG132 decreased the secretion of MCP-1 in the culture medium of RPE, but it
      increased the expression of IL-6 mRNA in RPE and IL-6 protein level in the
      culture medium of RPE. MG132 treatment was also found to enhance the level of
      phosphorylated p38 mitogen-activated protein kinases (MAPKs) and c-Jun N-terminal
      Kinase (JNK) by Western blotting. More importantly, the effect of MG132 on
      upregulating the levels of IL-6 was inhibited by SB203580, an inhibitor of P38
      MAP kinases. But the JNK inhibitor, SP600125, cannot prevent the effect of
      upregulating the levels of IL-6 by MG132 in the RPE culture medium. Conclusions:
      We concluded that the proteasome inhibitor, MG132, upregulates IL-6 production in
      RPE cells through the activation of P38 MAPKs.

PMID- 30116632
TI  - Analysis of Anthocyanins Extracted from the Acai Fruit (Euterpe oleracea): A
      Potential Novel Vital Dye for Chromovitrectomy.
AB  - Purpose: To classify and quantify anthocyanins in a vital dye extracted from the
      acai fruit (Euterpe oleracea), adjust pH and osmolarity, and perform
      lyophilization to develop a new chromovitrectomy dye. Methods: Three dye
      concentrations 10%, 25%, and 35% (equivalent to 100, 250, and 350 mg of
      lyophilized acai fruit pulp extract samples) were evaluated when diluted in 1 ml
      of phosphate-buffered solution (pH 7 and 300 mOsm). The dye was analyzed by mass
      spectrometry and high-performance liquid chromatography (HPLC) to identify and
      quantify anthocyanins molecules. Results: The pH and osmolarity correction and
      lyophilization were performed without damaging the anthocyanin molecular
      structure. Mass spectrometry confirmed the presence of five anthocyanins in the
      three concentrations of the dye. Cyanidin-3-O-glucoside was the major anthocyanin
      found. HPLC showed that the concentration of anthocyanin was similar, independent
      of the dye concentration tested. Conclusions: Lyophilization and the correction
      of pH and osmolarity (7.00 and 300 mOsm, resp.) were performed successfully. Five
      anthocyanins are present in the dye from the acai fruit. The major anthocyanin is
      cyanidin-3-O-glucoside. Independent of the dye concentration tested, the
      anthocyanin concentration was similar. Standardized chemical characteristics of
      this new dye may allow its use during chromovitrectomy in humans.

PMID- 30116633
TI  - Decorin, Tenascin C, Total Antioxidant, and Total Oxidant Level Changes in
      Patients with Pseudoexfoliation Syndrome.
AB  - Purpose: Pseudoexfoliation syndrome (PEX) is an eye disease that develops under
      the influence of regional population differences, genetic factors, age, and
      environmental factors and is characterized by visualization of a gray-white
      fibrogranular substance in the lens anterior capsule and/or pupil margin during
      anterior segment examination. The underlying biochemical mechanisms of the
      disease have not yet been fully elucidated. Therefore, this study was designed to
      show the changes in aqueous humor and blood serum levels of matrix
      metalloproteinases (decorin and tenascin C), total antioxidants (TAS), and total
      oxidants (TOS) in both cataract patients who have unilateral PEX material and
      cataract patients who do not have unilateral PEX material. Methods: Biological
      samples were simultaneously collected from 22 cataract patients who had
      unilateral pseudoexfoliation (PEX patients) and 22 cataract patients who did not
      have unilateral pseudoexfoliation (control patients). From the collected
      biological samples, decorin (DEC) and tenascin C (TN-C) were measured with the
      enzyme-linked immunosorbent assay (ELISA) method, and TAS and TOS were measured
      with an autoanalyzer. Results: When decorin, tenascin C, and TOS values of PEX
      patients were compared with those of control patients, there was a statistically
      significant increase in all three parameters. Conversely, TAS values showed a
      statistically significant decrease in PEX patients compared to controls. DEC, TN
      C, TAS values, and TOS values were significantly higher in aqueous fluid than in
      blood in both the PEX patient and control groups. Conclusions: We suggest that
      parameters such as DEC, TN-C, TAS, and TOS play a role in the etiopathology of
      pseudoexfoliation syndrome. Thus, bringing these increased levels of
      extracellular proteins and TOS and decreased levels of TAS back to within
      physiological limits can mediate the reorganization of the blood-aqueous fluid
      barrier and slow the progression of pseudoexfoliation syndrome.

PMID- 30116635
TI  - Extended Injection Intervals after Switching from Ranibizumab to Aflibercept in
      Macular Edema due to Central Retinal Vein Occlusion.
AB  - Purpose: To assess treatment interval extension after switching from ranibizumab
      to aflibercept intravitreal injections in macular edema (ME) due to central
      retinal vein occlusion (CRVO) with an insufficient response or frequent
      recurrences to initial treatment. Methods: CRVO eyes treated with ranibizumab
      injections on a treat-and-extend (TAE) basis with an insufficient response or
      frequent recurrences were switched to aflibercept. Primary endpoint was the
      change in injection intervals before and after the switch. Results: Eleven eyes
      were included in this retrospective bicentric study. Before switching, patients
      received a mean number of 15.3 ranibizumab injections (range, 6-34) during a mean
      follow-up of 23.4 months (range, 6-57). After switching to aflibercept, patients
      received a mean number of 12.4 injections (range, 6-20) during a mean follow-up
      of 25.5 months (range, 16-38). Treatment interval could be extended from 6.1
      (range, 4-8) to 11 weeks (range, 8-16) (p=0.001) corresponding to a mean
      extension of injection interval of +4.9 weeks. Conclusion: In case of
      insufficient response or frequent recurrences of ME due to CRVO in patients
      treated with ranibizumab on a TAE basis, switching to aflibercept could allow
      extending treatment intervals, which could reduce the injection burden for these
      patients.

PMID- 30116634
TI  - High Concentration of Glucose Increases Reactive Oxygen Species Generation and
      Apoptosis Induced by Endoplasmic Reticulum Stress Pathway in Rabbit Corneal
      Epithelial Cells.
AB  - Objective: To investigate the effect of high concentration of glucose on reactive
      oxygen species (ROS) production in rabbit corneal epithelial cells (RECEs) and
      explore whether the increased ROS initiates the apoptosis process of RECEs
      through oxidative stress and endoplasmic reticulum (ER) stress pathway. Methods:
      RECEs were treated by different concentrations of glucose for a while, and then
      the production of ROS was detected by flow cytometry. The expressions of PERK, p
      PERK, Akt, p-Akt, and CHOP were determined by western blot, and the cell
      viability was measured by Cell Counting Kit-8 (CCK-8). Flow cytometry was used to
      detect the early apoptosis rate. Meanwhile, the effects of N-acetyl-L-cysteine
      (NAC), an active oxygen inhibitor, on the experimental results were observed.
      Results: Compared with the normal glucose concentration group, the fluorescence
      intensity of ROS in the high concentration (1 mM glucose) of glucose group was
      significantly increased (P < 0.05). NAC-inhibited ROS production was induced by
      high concentration of glucose (P < 0.05).Western blot demonstrated that the
      expressions of the p-PERK and CHOP increased significantly (P < 0.05), the p-Akt
      expression decreased (P < 0.05), and the PERK and Akt expressions did not change
      significantly in the high concentration of glucose group compared to the normal
      concentration group. CCK-8 results revealed that compared with the normal
      concentration of glucose group, the cell activity of the high concentration of
      glucose group decreased. For the cells in the high concentration of glucose
      group, the cell survival rate of NAC-treated cells was higher than that of
      untreated (P < 0.05). The flow cytometry results indicated that the early
      apoptosis rate of the cells in the high concentration of glucose group increased
      in contrast with that in the normal concentration of glucose group (P < 0.05).
      Treating the cells in the high concentration of glucose group with NAC could
      reduce the cell apoptosis resulted from high glucose (P < 0.05). Conclusions:
      High concentration of glucose may induce the formation of ROS which leads to
      oxidative stress and ER stress in RECEs and even leads to cell apoptosis. The
      reactive oxygen inhibitor, NAC, can play a protective character in the high
      concentration of glucose environment. These results might provide theoretical
      basis for the study of the diabetes-related dry eye.

PMID- 30116636
TI  - Corrigendum to "Two-Year Outcome of Aflibercept in Patients with Pigment
      Epithelial Detachment due to Neovascular Age-Related Macular Degeneration (nAMD)
      Refractory to Ranibizumab".
AB  - [This corrects the article DOI: 10.1155/2017/8984313.].

PMID- 30116637
TI  - Retracted: Coronary Angiography Safety between Transradial and Transfemoral
      Access.
AB  - [This retracts the article DOI: 10.1155/2016/4013843.].

PMID- 30116638
TI  - Validating Left Ventricular Filling Pressure Measurements in Patients with
      Congestive Heart Failure: CardioMEMSTM Pulmonary Arterial Diastolic Pressure
      versus Left Atrial Pressure Measurement by Transthoracic Echocardiography.
AB  - Background: Routine ambulatory echocardiographic estimates of left ventricular
      (LV) filling pressures are not cost-effective and are occasionally fraught with
      anatomic, physiologic as well as logistical limitations. The use of implantable
      hemodynamic devices such as CardioMEMS Heart Failure (HF) System has been shown
      to reduce HF-related readmission rates by remote monitoring of LV filling
      pressures. Little is known about the correlation between CardioMEMS and
      echocardiography-derived estimates of central hemodynamics. Methods: We performed
      a prospective, single-center study enrolling seventeen participants with New York
      Heart Association functional class II-III HF and preimplanted CardioMEMS sensor.
      Simultaneous CardioMEMS readings and a limited echocardiogram were performed at
      individual clinic visits. Estimated left atrial pressure (LAP) by echocardiogram
      was calculated by the Nagueh formula. Linear regression was used as a measure of
      agreement. Variability between methods was evaluated by Bland-Altman analysis.
      Results: Mean age was 74 +/- 9 years; 59% (10/17) were males. LV systolic
      dysfunction was present in 76% (13/17) of subjects. Mean PAdP was 18 +/- 4 mmHg
      and 19 +/- 5 mmHg for CardioMEMS and echocardiographic-derived estimates,
      respectively, with a significant correlation between both methods (r2=0.798, p <=
      0.001). Conclusions: Our study illustrates a direct linear correlation between
      PAdP measured by CardioMEMS and simultaneous measurement of LV filling pressures
      derived by echocardiography.

PMID- 30116639
TI  - Women's Awareness and Associated Factors on Preconception Folic Acid
      Supplementation in Adet, Northwestern Ethiopia, 2016: Implication of Reproductive
      Health.
AB  - Introduction: Preconception folic acid supplementation is the provision of folate
      for reproductive age group women who have a plan to be pregnant. According to
      different studies, in African countries, there is poor utilization of
      preconception folic supplementation. So this study aimed at assessing women's
      awareness on preconception care and its associated factors in Adet, Northwestern
      Ethiopia. Methods: A community-based cross-sectional study was conducted from
      March 1 to April 1, 2016, among 422 reproductive age group women. Systematic
      random sampling was used to get the study unit, and the data were collected using
      pretested structured questionnaire via face-to-face interview. The collected data
      were entered, cleaned, checked using EpiData version 3.1, and finally analyzed
      using SPSS version 20. Descriptive summary of the data was presented in terms of
      percentage and frequency. Binary and multiple logistic regressions were used in
      order to identify predictors using odds ratio at 95% confidence interval. Result:
      In this study, a total of 422 reproductive age group women participated with a
      response rate of 100%. Of a total of 422 participants, 67 (15.9%) of the women
      had good awareness on preconception folic acid supplementation. Women's awareness
      on preconception folic acid supplementation was affected by having a chronic
      health problem, monthly household income, educational status, and a history of
      family planning use. Women who were educated (AOR 4.77, CI 1.85-6.98), had a
      history of family planning use (AOR 3.89, CI 1.77-8.55), had a chronic health
      problem (AOR 3.47, CI 2.68-5.98), and had a better monthly income (AOR 2.6, CI
      2.05-6.76) had good awareness than their counterparts. Conclusion and
      Recommendation: This study concluded that women's awareness on preconception
      folic acid supplementation was low. This finding suggests that there is a need to
      give emphasis and deliver health education about preconception folic acid
      supplementation for women.

PMID- 30116640
TI  - Association of Copper Status with Lipid Profile and Functional Status in Patients
      with Amyotrophic Lateral Sclerosis.
AB  - Oxidative stress is one of the main mechanisms associated with the pathogenesis
      of amyotrophic lateral sclerosis (ALS). Copper can affect cellular oxidation and
      lipid metabolism. The aim of this study was to evaluate the association of copper
      status with lipid profile and functional status in patients with ALS. A cross
      sectional study was carried out including 27 patients with ALS (case group) and
      26 healthy individuals (control group). Copper status was evaluated by habitual
      dietary copper intake, plasma copper, and serum ceruloplasmin concentrations. The
      lipid profile included analysis of serum total cholesterol (TC), LDL-cholesterol
      (LDL-c), HDL-cholesterol (HDL-c), and triglycerides (TGL). The functional status
      of patients with ALS was assessed by the ALS Functional Rating Scale-Revised
      (ALSFRS-R). In the case group, plasma copper was lower compared with the control
      group (133.9 versus 164.1 MUg/dL, p=0.0001) and was positively correlated with
      HDL-c (rs=0.398, p=0.044). In the control group, plasma copper was positively
      correlated with serum ceruloplasmin (rs=0.646, p < 0.001), TC (rs=0.446,
      p=0.025), LDL-c (rs=0.445, p=0.029), and HDL-c (rs=0.479, p=0.015), and serum
      ceruloplasmin was positively correlated only with LDL-c (rs=0.407, p=0.043). In
      the case group, dietary copper intake (B=-0.373, p < 0.001), plasma copper (B=
      0.005, p=0.033), and TC (B=-0.312, p=0.001) were inversely associated with the
      functional status of patients with ALS. In contrast, serum ceruloplasmin
      (B=0.016, p=0.044), LDL-c (B=0.314, p=0.001), HDL-c (B=0.308, p=0.001), and TGL
      (B=0.062; p=0.001) were positively associated with their functional status. In
      conclusion, this study suggests a disturbance of copper status and its connection
      with the lipid profile in patients with ALS. Furthermore, copper status and lipid
      profile may influence the functional status of patients with ALS, standing out as
      potential biomarkers of disease severity.

PMID- 30116641
TI  - Understanding the Relationship between Atherogenic Index of Plasma and
      Cardiovascular Disease Risk Factors among Staff of an University in Malaysia.
AB  - Background: Atherogenic index of plasma (AIP) was found to be one of the
      strongest markers in predicting the cardiovascular disease (CVD) risk. This study
      was to determine the AIP and its relationship with other CVD risk factors.
      Materials and Methods: This cross-sectional study was done among 349 staff of a
      public university in Sarawak. Data were collected using questionnaire, blood
      sampling, and anthropometric and blood pressure measurement. Data were analyzed
      using IBM SPSS version 20. Results: A total of 349 respondents participated with
      majority females (66.8%), aged 38.5 +/- 7.82 years. Nearly 80% of the respondents
      were overweight and obese, 87.1% with high and very high body fat, and 46.9% with
      abnormal visceral fat. For AIP category, 8.9% were found to be in intermediate
      and 16.4% were at high risk. Elevated lipid profile showed that total cholesterol
      (TC) is 15.5%, low density lipoprotein (LDL) is 16.1%, and triglyceride (TG) is
      10.6%. AIP was significantly correlated with body mass index (r=0.25), visceral
      fat (r=0.37), TC (r=0.22), LDL (0.24), HDL (r=-0.72), TG (r=0.84), glucose
      (r=0.32), systolic blood pressure (r=0.22), and diastolic blood pressure
      (r=0.28). Conclusion: It indicated that AIP is associated with other CVD risk
      factors. Modification of lifestyle is strongly recommended.

PMID- 30116642
TI  - The Mysterious Mitral Mass: A Case of Valvular Myxoma.
AB  - Myxomas are the most common benign cardiac neoplasms in adults. The vast majority
      of cardiac myxomas arise from the left atrium near the fossa ovalis of the intra
      atrial septum. There have been reports of myxomas arising from the ventricles
      accounting for about 5% of cases. In our literature review, we have found 55
      reported cases of myxomas originating from the mitral valve reported in the adult
      population dating back to 1871. The majority of these cases presented with
      embolic complications or syncope. We present an incidental mitral valve myxoma
      which we excised in efforts to prevent debilitating complications.

PMID- 30116643
TI  - Clozapine-Induced Myocarditis or Acute Coronary Syndrome? Optical Coherence
      Tomography to the Rescue.
AB  - Chest pain and troponin elevation may be due to an acute coronary syndrome,
      myocarditis, acute cardiomyopathy, or other less common conditions. Management
      differs depending on the aetiology, and the pathophysiologic diagnosis has direct
      implications on treatment and patient outcomes. History and clinical examination
      is supplemented by selected investigations including the electrocardiogram, chest
      X-ray, echocardiography, coronary angiography, and even myocardial perfusion
      scintigraphy or cardiac magnetic resonance imaging. Intravascular imaging can
      provide important insights into the underlying mechanism of acute coronary
      syndromes, especially when angiography is ambiguous.

PMID- 30116644
TI  - Successful Treatment of Occlusive Left Main Coronary Artery Dissection by Impella
      Supported Stenting.
AB  - We report successful treatment of a patient, who, during diagnostic angiography,
      developed an ostial left main coronary artery dissection with stump occlusion of
      the vessel. First, mechanical circulatory support with an Impella CP device was
      established. Then, patency of the left coronary system was achieved by placement
      of stents in the left anterior descending, left circumflex, and left main
      coronary arteries. On completion of the procedure, left ventricular systolic
      function, as assessed by echocardiography, was normal. At 24-month clinical
      follow-up, the patient remains angina-free and well. This is the first reported
      case of the use of an Impella device to support treatment of iatrogenic left main
      coronary artery dissection.

PMID- 30116645
TI  - A Combined Approach for the Aesthetic Management of Stained Enamel Opacities:
      External Bleaching Followed by Resin Infiltration.
AB  - Stained enamel opacities are frequently encountered in dental practice. However,
      due to the risk of unaesthetic outcome, managing such lesions by resin
      infiltration techniques alone is not advised. Therefore, performing external
      bleaching before resin infiltration procedure is mandatory to eliminate stains
      from the hypomineralized lesions in order to aesthetically infiltrate them. In
      this work, we describe clinical cases in which external bleaching and resin
      infiltration techniques were used for managing stained enamel hypomineralized
      lesions related to traumatic dental injuries and molar incisor
      hypomineralization. Despite the fact that this approach has some limitations, it
      could be concluded that external bleaching associated with the resin infiltration
      technique shows promising results to aesthetically manage stained enamel
      opacities when the stain is totally removed after bleaching.

PMID- 30116646
TI  - Intraoral Sebaceous Carcinoma: Case Report of a Rare Tumor Emphasizing the
      Histopathological Differential Diagnosis.
AB  - Background: Sebaceous carcinoma (SC) is an uncommon cutaneous malignancy, usually
      occurring predominantly in the eyelids and only occasionally involving the oral
      cavity. Sebaceous carcinoma (SC) is a rare malignancy. Only 10 cases of sebaceous
      carcinoma of the oral cavity have been reported so far. Case Presentation: A 40
      year-old female presented with a mass on the left side of the middle third of the
      face. Radiographic findings were inconclusive. Resection of the mass was
      consistent with the diagnosis of primary sebaceous carcinoma. Conclusion:
      Intraoral sebaceous carcinoma is uncommon. Due to its varied clinical appearance
      and presence of a diverse histopathologic appearance, the diagnosis is quite
      often confounding and elusive. Hence, it is imperative to familiarize oneself
      about various aspects of this rare tumor for earlier diagnosis, to improve the
      chances of patient's survival.

PMID- 30116647
TI  - Myasthenia Gravis Presenting as Graft versus Host Disease after Allogeneic Blood
      Stem Cell Transplant.
AB  - Myasthenia gravis is a very rare manifestation of graft versus host disease after
      stem cell transplants. Herein, we describe a case of new-onset myasthenia gravis
      after a stem cell transplant 34 months ago in a patient with myelodysplastic
      syndrome.

PMID- 30116648
TI  - Kinetic Studies on the Removal of Some Lanthanide Ions from Aqueous Solutions
      Using Amidoxime-Hydroxamic Acid Polymer.
AB  - Lanthanide metal ions make distinctive and essential contributions to recent
      global proficiency. Extraction and reuse of these ions is of immense significance
      especially when the supply is restricted. In light of sorption technology,
      poly(amidoxime-hydroxamic) acid sorbents are synthesized and utilized for the
      removal of various lanthanide ions (La3+, Nd3+, Sm3+, Gd3+, and Tb3+) from
      aqueous solutions. The sorption speed of trivalent lanthanides (Ln3+) depending
      on the contact period is studied by a batch equilibrium method. The results
      reveal fast rates of metal ion uptake with highest percentage being achieved
      after 15-30 min. The interaction of poly(amidoxime-hydroxamic) acid sorbent with
      Ln3+ ions follows the pseudo-second-order kinetic model with a correlation
      coefficient R2 extremely high and close to unity. Intraparticle diffusion data
      provide three linear plots indicating that the sorption process is affected by
      two or more steps, and the intraparticle diffusion rate constants are raised
      among reduction of ionic radius of the studied lanthanides.

PMID- 30116649
TI  - A Facile Synthesis of Highly Nitrogen-Doped Carbon Dots for Imaging and Detection
      in Biological Samples.
AB  - A facile, green, and high-output hydrothermal synthesis was proposed for the
      fabrication of highly fluorescent nitrogen-doped carbon quantum dots (N-doped
      CDs). The nitrogen content in N-doped CDs reached 19.2% and demonstrated strong
      blue fluorescence emission was obtained with fluorescence quantum yield (QY) of
      up to 32.9%, which exhibit high fluorescence quantum yield, high photostability,
      and excellent biocompatibility. The N-doped CDs possess high photostability, low
      toxicity, and excellent biocompatibility, based on which the N-doped CDs were
      successfully applied as a fluorescence probe for cell imaging. Moreover, it was
      then successfully demonstrated for sensitive and selective detection of Fe3+ in
      serum.

PMID- 30116651
TI  - Pharmacokinetics and Bioavailability Study of Tubeimoside I in ICR Mice by UPLC
      MS/MS.
AB  - The aim of this study is to establish and validate a rapid, selective, and
      sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC
      MS/MS) method to determine tubeimoside I (TBMS-I) in ICR (Institute of Cancer
      Research) mouse whole blood and its application in the pharmacokinetics and
      bioavailability study. The blood samples were precipitated by acetonitrile to
      extract the analytes. Chromatographic separation was performed on a UPLC BEH C18
      column (2.1 mm * 50 mm, 1.7 MUm). The mobile phase consisted of water with 0.1%
      formic acid and methanol (1 : 1, v/v) at a flow rate of 0.4 mL/min. The total
      eluting time was 4 min. The TBMS-I and ardisiacrispin A (internal standard (IS))
      were quantitatively detected by a tandem mass spectrometry equipped with an
      electrospray ionization (ESI) in a positive mode by multiple reaction monitoring
      (MRM). A validation of this method was in accordance with the US Food and Drug
      Administration (FDA) guidelines. The lower limit of quantification (LLOQ) of TBMS
      I was 2 ng/mL, and the calibration curve was linearly ranged from 2 to 2000 ng/mL
      (r2 >= 0.995). The relative standard deviation (RSD) of interday precision and
      intraday precision was both lower than 15%, and the accuracy was between 91.7%
      and 108.0%. The average recovery was >66.9%, and the matrix effects were from
      104.8% to 111.0%. In this assay, a fast, highly sensitive, and reproducible
      quantitative method was developed and validated in mouse blood for the first
      time. The absolute availability of TBMS-I in the mouse was only 1%, exhibiting a
      poor oral absorption.

PMID- 30116650
TI  - A Simple Separation Method of the Protein and Polystyrene Bead-Labeled Protein
      for Enhancing the Performance of Fluorescent Sensor.
AB  - Dielectrophoresis- (DEP-) based separation method between a protein, amyloid beta
      42, and polystyrene (PS) beads in different microholes was demonstrated for
      enhancement of performance for bead-based fluorescent sensor. An intensity of
      ?|E|2 was relative to a diameter of a microhole, and the diameters of two
      microholes for separation between the protein and PS beads were simulated to 3
      MUm and 15 MUm, respectively. The microholes were fabricated by
      microelectromechanical systems (MEMS). The separation between the protein and the
      PS beads was demonstrated by comparing the average intensity of fluorescence
      (AIF) by each molecule. Relative AIF was measured in various applying voltage and
      time conditions, and the conditions for allocating the PS beads into 15 MUm hole
      were optimized at 80 mV and 15 min, respectively. In the optimized condition, the
      relative AIF was observed approximately 4.908 +/- 0.299. Finally, in 3 MUm and 15
      MUm hole, the AIFs were approximately 3.143 and -1.346 by 2 nm of protein and
      about -2.515 and 4.211 by 30 nm of the PS beads, respectively. The results showed
      that 2 nm of the protein and 30 nm of PS beads were separated by DEP force in
      each microhole effectively, and that our method is applicable as a new method to
      verify an efficiency of the labeling for bead-based fluorescent sensor ?|E|2.

PMID- 30116652
TI  - Development of QuEChERS Method for the Determination of Polycyclic Aromatic
      Hydrocarbons in Smoked Meat Products Using GC-MS from Qatar.
AB  - A simple and fast method for the determination of PAHs in smoked meat samples was
      described. The QuEChERS (Z-Sep) procedure was used for sample preparation. Gas
      chromatograph-mass spectrometer with electron ionization (EI) was used to
      separate and detect the PAHs. All 16 common PAHs were analyzed successfully.
      Matrix-matched calibration was applied. Spiked samples were performed at 1 ng/g
      (n=10) and 10 ng/g (n=10) for two days. Overall recoveries of PAHs were within 74
      to 117%, with RSDs within 1.15 to 37.57% and 1 and 10 ng/g wet weight for first
      and second day, respectively. In most of the analyzed smoked meat samples, there
      were no exceeded levels compared to the maximum levels declared by Commission
      Regulation (EU) number 835/2011. The method can be recommended for routine
      analysis for laboratories having a large number of samples.

PMID- 30116653
TI  - A Post-pleistocene Calibrated Mutation Rate from Insect Museum Specimens.
AB  - Quantifying the age of recent species divergence events can be challenging in the
      absence of calibration points within many groups. The katydid species
      Neoconocephalus lyristes provides the opportunity to calibrate a post
      Pleistocene, taxa specific mutation rate using a known biogeographic event, the
      Mohawk-Hudson Divide. DNA was extracted from pinned museum specimens of N.
      lyristes from both Midwest and Atlantic populations and the mitochondrial gene
      COI sequenced using primers designed from extant specimens. Coalescent analyses
      using both strict and relaxed molecular clock models were performed in BEAST
      v1.8.2. The assumption of a strict molecular clock could not be rejected in favor
      of the relaxed clock model as the distribution of the standard deviation of the
      clock rate strongly abutted zero. The strict molecular clock model resulted in an
      intraspecific calculated mutation rate of 14.4-17.3 %/myr, a rate substantially
      higher than the common rates of sequence evolution observed for insect
      mitochondrial DNA sequences. The rate, however, aligns closely with mutation
      rates estimated from other taxa with similarly recent lineage divergence times.

PMID- 30116654
TI  - Towards superior dendritic-cell vaccines for cancer therapy.

PMID- 30116656
TI  - The role of dermoscopy in a topical steroid-damaged face.

PMID- 30116655
TI  - Bullous pemphigoid induced by Hijama therapy (cupping).
AB  - Bullous pemphigoid (BP) is described as a subepidermal blistering disorder, which
      is commonly reported among the elderly, particularly those older than 60 years of
      age. In this report, we present the case of a 41-year-old female patient with BP
      lesions that were initially detected at the site of Hijama therapy with a
      subsequent generalized spread. Punch biopsy from the lesions and perilesional
      direct immunofluorescence (DIF) demonstrated features of BP. The anti-BP180 level
      was 178 RU/mL, and the anti-BP230 level was negative. BP antigens at the site of
      Hijama caused an antibody response, which led to widespread blistering over the
      trunk due to epitope spreading. In a comprehensive review of the literature, a
      total of 22 BP patients with lesions due to physical trauma were studied, and
      clinical, immunological, and epidemiological information was gathered. This
      article is the first report on the occurrence of BP induced by Hijama therapy.

PMID- 30116657
TI  - Cryotherapy versus CO2 laser in the treatment of plantar warts: a randomized
      controlled trial.
AB  - Background: Warts are one of the most common infections in humans. Plantar warts
      are a subtype of non-genital warts, and several procedures and topical treatments
      have been used in its treatment. Cryotherapy is one of the most popular
      modalities, but it is time-consuming and remission rates vary in different
      studies. CO2 laser was the first laser used for treating warts. To date, no
      clinical trial has been done to compare CO2 laser with cryotherapy in the
      treatment of plantar warts. Patients and Methods: This randomized controlled
      trial was performed in order to compare the efficacy and number of sessions
      needed to treat plantar warts in 60 patients who had received no previous
      treatment in the previous 3 months. They were randomly allocated to the
      cryotherapy or CO2 laser group. The number of sessions needed for response and
      the recurrence rate after a 3-month follow-up was compared in the 2 groups.
      Results: Sixty patients with plantar warts were randomly allocated to either the
      CO2 laser or cryotherapy groups. Median age was 25 (range=18-53) and 27 (range=
      18-75) years in the cryotherapy group and CO2 laser groups, respectively. Both
      groups were matched for age and sex (56% male and 44% female in the cryotherapy
      group and 34% male and 66% female in the CO2 laser group). The median number of
      sessions needed for complete resolution of the warts in the CO2 laser and
      cryotherapy groups were 1 (range=1-2) and 3 (range=1-12), respectively. The
      difference in the number of sessions was statistically significant between the 2
      groups (P-value<=0.001). Recurrence rates after a 3-month follow-up was not
      statistically significant (P-value= 0.069). Conclusion: The number of sessions
      needed to treat plantar warts was less using CO2 laser than cryotherapy;
      therefore, this modality can be a good addition to the already existing anti-wart
      armamentarium.

PMID- 30116658
TI  - Dermoscopy of a single plaque on the face: an uncommon presentation of cutaneous
      sarcoidosis.
AB  - Sarcoidosis is a multisystemic granulomatous disease of unknown causes, and
      cutaneous sarcoidosis (CS) is an early manifestation of the disease. Dermoscopy
      has gained increasing interest in the past few years as an aid in the clinical
      diagnosis of inflammatory and infectious skin manifestations. We present a case
      report about a single, erythematous, and asymptomatic plaque on the face with
      unexpected dermoscopy characteristics of CS. Learning points: CS on the face of a
      therapy-resistant actinic keratosis should be considered a differential
      diagnosis.Dermoscopy can change the diagnosis and lead to the correct management.

PMID- 30116659
TI  - An eruption of yellow-red papules on the trunk, arms, and legs of an adult.

PMID- 30116660
TI  - Lichen planus-like keratosis: clinical applicability of in vivo reflectance
      confocal microscopy for an indeterminate cutaneous lesion.
AB  - Lichen planus-like keratosis (LPLK) is an involuting cutaneous lesion often
      presenting between the fifth and seventh decades of life. These lesions typically
      appear abruptly as a solitary macule, papule, or plaque that continuously evolves
      as it undergoes regression. Clinical and dermoscopic features of LPLK can mimic
      both benign and malignant lesions, often prompting biopsy for accurate diagnosis.
      We describe a case of LPLK developing in a patient with a history of multiple
      skin cancers, including melanoma. Dermoscopy revealed peripheral granules and a
      central area with pinkish-brown pigmentation and a disorganized pattern with
      shiny white structures and rosettes. Handheld reflectance confocal microscopy
      (RCM) showed a typical honeycomb pattern with millia-like cysts and comedo-like
      openings, and lacked pagetoid and dendritic cells. Based on the benign features
      seen with RCM, the lesion was followed until complete regression was observed. In
      conclusion, we describe a case of LPLK with clinically and dermoscopically
      indeterminate features that was successfully monitored with RCM. We intend to
      highlight the utility of RCM as a diagnostic aid in equivocal lesions in order to
      prevent unnecessary excisional procedures.

PMID- 30116661
TI  - Subcutaneous scalp nodule as the presenting symptom of systemic light-chain
      amyloidosis.
AB  - We present a case of subcutaneous nodular amyloidosis mimicking a pilar cyst.
      Further evaluation led to the diagnosis of malignant systemic light-chain
      amyloidosis. The epidemiology and histopathological features of light-chain
      amyloidosis with cutaneous involvement are reviewed, as well as current
      recommendations for initial evaluation.

PMID- 30116662
TI  - Challenging facial pigmented lesions: values and limits of confocal microscopy.

PMID- 30116663
TI  - Obligate and facultative paraneoplastic dermatoses: an overview.
AB  - Dermatological paraneoplastic syndromes are a group of cutaneous diseases
      associated with malignancy, but not directly related to the primary tumor itself
      or to its metastases. It is of utmost importance for the dermatologist to
      recognize the major cutaneous paraneoplastic syndromes to diagnose the underlying
      tumors that trigger them as early as possible. In this overview, skin conditions
      that are highly correlated with malignancy, whose recognition implies a mandatory
      investigation of internal cancer, are described.

PMID- 30116664
TI  - Dermatoscopy of flat pigmented facial lesions-evolution of lentigo maligna
      diagnostic criteria.
AB  - Recognition of facial lentigo maligna (LM) is often difficult, particularly at
      early stages. Algorithms and multivariate diagnostic models have recently been
      elaborated on the attempt to improve the diagnostic accuracy. We conducted a
      cross-sectional and retrospective study to evaluate dermatoscopic criteria aiding
      in diagnosis of flat pigmented facial lesions (FPFL). We examined 46 FPFL in 42
      Caucasian patients and found that 4 of 20 dermatoscopic criteria reached the
      significance level required for features indicating malignancy namely,
      hyperpigmented follicular openings, obliterated follicular opening, annular
      granular structures, and pigment rhomboids. Concomitant presence of at least 2 or
      3 of the 4 mentioned criteria was significantly more frequent in LM than in
      pigmented actinic keratosis (PAK). However, despite more frequently seen in LM,
      these features were also displayed in some of the PAK and other FPFL, so we found
      them not specific for LM. Although dermatoscopy enhances the diagnostic accuracy
      in evaluating FPFL, histopathology remains the gold standard for correct
      diagnosis, making evident the need for improvements in early noninvasive
      diagnosis of LM.

PMID- 30116665
TI  - Digital dermatoscopy as a useful tool for evaluating therapeutic efficacy in a
      patient with eruptive keratoacanthomas.

PMID- 30116666
TI  - Potential utility of dermoscopy in the examination of ocular pigmentations.
AB  - Background: Dermoscopy is a fundamental method in the examination of melanocytic
      neoplasms. Limited data exist about the dermoscopic features of ocular
      pigmentations (OPs). Objectives: We aimed to investigate the usefulness of
      dermoscopy in the examination of OPs. Methods: Dermoscopic images of OPs of 20
      consecutive patients were recorded. Impression cytology (IC) was performed to
      these lesions. Dermoscopic images were evaluated for specific dermoscopic
      structures and patterns without knowing the cytological examination results.
      Results: Fifteen percent (3/20) of the lesions presented with suspicious
      cytological findings. More of the suspicious lesions had 4 colors compared to
      benign lesions (66.7% vs 11.8%, p=0.088). This was also determined for blue-gray
      (66.7% vs 11.8%, p=0.088) and white (66.7% vs 17.7%, p=0.14) colors. At least 3
      structures were observed in all suspicious lesions (100%), but were observed in
      only in 41.2% of benign lesions (p=0.105). Besides, two-thirds of suspicious
      lesions had more than 4 structures, but none of the benign lesions reported this
      (p=0.016). Most of the benign lesions showed asymmetry in one axis (93.3%),
      whereas all suspicious lesions showed asymmetry in 2 axes (p=0.004). Conclusions:
      Dermoscopy seems to be a useful method in the evaluation of OPs. The existence of
      dermoscopic patterns, colors, and dermoscopic structure plurality and asymmetry
      raise suspicion in OPs, similarly to skin pigmentations. Dermatologists should be
      aware of the ocular area, and closer collaboration should be developed between
      dermatologists and ophthalmologists in the management of pigmented lesions.

PMID- 30116668
TI  - Asymptomatic heterogeneously black-pigmented plaque in a 58-year-old man: an
      unusual presentation of a melanoma mimicker.

PMID- 30116669
TI  - Use of dermatoscopy in the detection of squamous cell carcinoma in a patient with
      recessive dystrophic epidermolysis bullosa.

PMID- 30116667
TI  - Recent trends in teledermatology and teledermoscopy.
AB  - Teledermatology is a useful alternative where specialized dermatological
      assistance is not available and has been used successfully to support health
      professionals in a wide range of settings worldwide, in either an asynchronous
      store-and-forward format or a real-time video conferencing format.
      Teledermoscopy, which includes dermoscopic images in the teleconsultation, is
      another addition that improves remote assessments of pigmented lesions. A more
      recent variant is mobile teledermoscopy, which uses a smartphone to deliver the
      same type of service. Teledermoscopy's greatest strength may be as a triage and
      monitoring tool, as it can reduce the number of unnecessary referrals, wait
      times, and the cost of providing and receiving dermatological care. While face-to
      face (FTF) care remains the gold standard for diagnosis, drawbacks of not using
      FTF care as the primary method can be mitigated if teleconsultants are willing to
      refer to FTF care whenever there is uncertainty. Teledermatology has generally
      been well accepted by patients and practitioners alike. Barriers to the large
      scale use of teledermatology remain. Assigning medicolegal responsibility and
      instituting a reimbursement system are critical to promoting widespread use by
      medical professionals, while privacy and security features and a mechanism to
      link teleconsultations to patients' existing health records are essential to
      maximize patient benefit. Direct-to-consumer services also need attention from
      regulators to ensure that consumers can enjoy the benefits of telemedicine
      without the dangers of unregulated or untested platforms.

PMID- 30116670
TI  - Sequential digital dermatoscopic imaging of patients with multiple atypical nevi.
AB  - Patients with multiple atypical nevi are at higher risk of developing melanoma.
      Among different techniques, sequential digital dermatoscopic imaging (SDDI) is a
      state-of-the art method to enhance diagnostic accuracy in evaluating pigmented
      skin lesions. It relies on analyzing digital dermatoscopic images of a lesion
      over time to find specific dynamic criteria inferring biologic behavior. SDDI can
      reduce the number of necessary excisions and finds melanomas in an early-and
      potentially curable-stage, but precautions in selecting patients and lesions have
      to be met to reach those goals.

PMID- 30116671
TI  - Squamous cell carcinoma of the nail unit.
AB  - Squamous cell carcinoma (SCC) of the nail apparatus is a rare malignant tumor
      that usually originates underneath the nail plate and grows slowly with possible
      bone invasion. The etiology remains unknown, although a strong association with
      different conditions, such as high-risk human papillomavirus (HPVs), trauma, or
      radiation exposure has been demonstrated. Nail SCC is called "the great mimicker
      nail tumor" because different clinical presentations may coexist, resembling
      benign or malignant nail lesions. For this reason, there is often a significant
      delay between the onset of nail SCC and the diagnosis. Clinical manifestation
      includes onycholysis and erythema, while in the advanced stages nail ulceration
      can be observed. The association with pain, swelling, and inflammation usually
      indicates an invasive SCC with involvement of the underlying bone. Metastasis is
      rare but possible with involvement of lymph nodes. A multidisciplinary approach
      to assessment, management, and follow-up is advised. Using careful examination
      and modern diagnostic methods, including onychoscopy, biopsy, and histopathology,
      will help identify SCC and prevent the invasive progression. X-ray is important
      to investigate the bone invasion to determine the best surgical approach that
      will have satisfying cosmetic and functional outcomes. Nevertheless, local
      excision with sufficient surgical margins, best if using Mohs surgery, is usually
      sufficient and superior to amputation of the distal phalanx. This review aims to
      highlight the correct approach in suspected SCC of the nail unit.

PMID- 30116672
TI  - Giant clear cell acanthoma with dermatoscopic white lines.

PMID- 30116674
TI  - Granulomatous Diverticulitis: Who Would Have Thought!
AB  - Diverticular disease (DD) can have different presentations, including chronic
      colitis. However, diverticular disease-associated colitis (DAC) is a separate
      entity that can be associated with a granulomatous inflammation. DAC usually
      affects the left colon with no involvement of the cecum and the ascending colon.
      In this setting, Crohn's disease is high in the differential diagnosis. Although
      granulomatous colitis associated with diverticulosis has been previously
      described, this is the first case affecting the right colon to be reported in the
      English literature according to our search of the PubMed database. The patient
      presented with a tumor-like mass abutting the right colon that was further
      diagnosed as a granulomatous reaction secondary to DAC.

PMID- 30116673
TI  - Extradigital Glomus Tumor with Atypical Neuritis Presentation.
AB  - Glomus tumors are rare tumors of the arteriovenous junction that play a role in
      temperature regulation. They are most commonly found in the subungual finger. We
      present the case of a 77-year-old female with a chief complaint of a painful mass
      in her ulnar wrist. The differential diagnosis at the time was broad. Following a
      detailed history and physical exam, the etiology was believed to be that of a
      peripheral nerve sheath tumor. The patient was taken to the operating room for
      resection and biopsy of the mass. Histological evaluation confirmed that the mass
      was a glomus tumor. Our patient's symptoms had completely resolved and functional
      status had improved to baseline by the time of her two-week postoperative clinic
      visit. This case report demonstrates the many complexities in the diagnosis of a
      glomus tumor and the important role of surgical treatment in obtaining relief
      from extradigital glomus tumors.

PMID- 30116675
TI  - A Rare Case of Multiple Anomalies of the Coronary Arteries.
AB  - Coronary artery anomalies represent a rare phenomenon, which is observed in
      approximately 1% of the population. Although not a frequent anomaly, they may
      lead to complications during various procedures and can sometimes present with
      angina pectoris or myocardial infarction. Herein, we present a rare case of a
      patient with origin of the left main coronary artery from the right sinus of
      Valsalva combined with a superdominant right coronary artery due to a hypoplastic
      left circumflex artery. A 67-year-old male patient presented with symptoms of
      chest pain on exertion, which lasted for approximately 10 minutes and resolved
      after rest. Physical examination, auscultation, electrocardiogram, and
      transthoracic echocardiography revealed normal findings. Cardiac enzymes were
      within the reference ranges, while the levels of triglycerides and low density
      lipoprotein (LDL)-cholesterol were elevated. The patient was further evaluated
      through coronary angiography. It revealed the origin of the left coronary artery
      from the right sinus of Valsalva, with a markedly hypoplastic left circumflex
      artery and the presence of a 'superdominant' right coronary artery.
      Atherosclerotic lesions were not observed, and the symptoms were discussed to
      have been caused by the anomalous pattern of the coronary arteries and the
      hypoplastic left circumflex artery in particular. The most common symptom of a
      hypoplastic or absent left circumflex artery is chest pain on exertion which is
      explained by the 'steal' phenomenon - due to increased demand in the area
      normally supplied by the left circumflex artery, a transitory ischemia occurs in
      the basins supplied by the left anterior descending artery and the right coronary
      artery. These findings were similar to our case. Such variations, although mostly
      asymptomatic, can sometimes lead to serious cardiovascular conditions and should
      be considered by clinicians during the assessment of cardiac symptoms.

PMID- 30116676
TI  - A Case Report of Revision Total Knee Arthroplasty After 17 Years: All Grown Up,
      What Happens When Implants Mature?
AB  - The number of total knee arthroplasties (TKAs) being performed annually is
      steadily rising. Recommendations for clinical follow-up guidelines following
      these arthroplasties is controversial, with no strict guidelines for long-term
      follow up. Although a few case series exist which identify a minority of patients
      who require revision TKA for aseptic loosening or pain more than 15 years after
      index surgery, no published studies have yet described these patients or the
      pathology present at the time of surgery in detail. We present the case of a
      patient who underwent revision TKA for pain and instability that developed 17
      years after index surgery. Postoperative pathology revealed foreign body giant
      cell reaction of the tissue surrounding the previous implant. This case of
      revision after more than 17 years attempts to improve our understanding of long
      term reactions to implants and highlights the necessity of long-term follow up in
      patients with TKA. It is one of the longest follow-ups of TKA reporting long-term
      anatomic changes at the bone cement interphase and around the implant.

PMID- 30116677
TI  - Dosage Adjustments for Chemotherapy and Targeted Therapies in Colorectal and
      Pancreatic Cancer Patients with Hepatic Impairment.
AB  - There are many novel chemotherapeutic options and targeted therapies available
      for the treatment of colorectal and pancreatic cancer. Patients with these
      cancers often have hepatic impairment either from the metastasis to the liver or
      from the chemotherapy or targeted therapies used to treat the disease. It is
      important to describe the effects of these agents in patients with hepatic
      impairment. This article will review the dosage recommendations for the
      chemotherapy regimens and targeted therapies in colorectal and pancreatic cancer
      patients in the setting of hepatic impairment.

PMID- 30116678
TI  - Brugada Syndrome: The Role of Risk Stratification in Selecting Patients for
      Implantable Cardioverter-defibrillator Placement.
AB  - Brugada syndrome (BS) is an inherited cardiac ion channelopathy that is a rare,
      but treatable, cause of sudden cardiac death (SCD). There are many studies that
      explore the management of symptomatic BS, but few trials have been conducted
      regarding management of asymptomatic Brugada patients. Asymptomatic BS patients
      are shown to be at increased risk (0.5%-1.5%) for SCD compared to the general
      population and account for nearly 20% of deaths from SCD in patients with
      structurally normal hearts. Treatment for asymptomatic BS patients is often
      debated with the current guidelines allowing for management decisions to be made
      on a case-by-case basis. Therapies include either anti-arrhythmic medications,
      implantable cardioverter-defibrillator (ICD) placement, or no active treatment.
      This review intended to assess whether ICD placement benefits asymptomatic BS
      patients and what criteria may be useful in selecting patients for ICD placement.
      Results showed that ICD placement can reduce mortality in select asymptomatic
      patients. There were certain risk factors that increased the likelihood that an
      asymptomatic patient would experience SCD and thus benefit from an ICD. These
      factors include an electrocardiogram(ECG) demonstrating spontaneous type 1
      Brugada Syndrome and inducibility of ventricular tachyarrhythmias during
      electrophysiological study. Other variables including gender, family history of
      SCD, and the presence of SCN5A mutation were not predictive of arrhythmic events.
      Moreover, many patients can suffer complications from ICDs that can affect the
      quality of life including inappropriate shocks, device malfunction, infection,
      mental health problems, and difficulties with replacements. Guidelines for
      quantifying the risk of SCD relative to the risks associated with ICD placement
      are still poorly defined. These complications and risk factors should be taken
      into consideration in the context of a patient-centered discussion regarding ICD
      placement in asymptomatic patients.

PMID- 30116679
TI  - Referring Service Effect on Muscle Biopsy Diagnosis and Management in Myopathy.
AB  - Introduction Requests for muscle biopsy for evaluation of myopathy originate from
      a variety of different specialties. It is unknown whether the specialty of the
      referring service affects the likelihood of diagnostic biopsy or the therapeutic
      usefulness of a biopsy. Methods We reviewed 106 consecutive muscle biopsies
      requested by healthcare providers in neurology, rheumatology, family medicine,
      oncology, and gastroenterology. We tested for an association between referring
      service and whether the biopsy yielded a definitive pathology result or provided
      therapeutically useful results. Results Half of the biopsies (49%) returned
      definitive pathology and 88% of the biopsies provided information that
      contributed to therapeutic decisions. The diagnostic yield for muscle biopsies
      referred by different services was not statistically significant (p-value 0.1344)
      nor was the therapeutic yield statistically significant for muscle biopsies
      referred by different services (p-value 0.5525). Discussion The specialty of the
      service that requests a muscle biopsy does not influence the likelihood of
      obtaining a definitive pathological diagnosis or therapeutically useful
      information. Other factors may be more important in determining the likelihood of
      obtaining a clinically useful biopsy result.

PMID- 30116680
TI  - Generalized Edema Caused by Albiglutide: A Case Report.
AB  - Albiglutide is a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist
      administered by weekly injection. Albiglutide-treated patients experience
      incidences of adverse effects, including cardiovascular, renal, and
      gastrointestinal symptoms and injection-site reactions. We report the first case
      of generalized edema induced by albiglutide. We present a 35-year-old female with
      type-2 diabetes. She developed generalized edema after the start of albiglutide.
      Her physical examination and all the laboratory tests, including thyroid function
      tests, albumin level test, and renal function test were unremarkable, and did not
      explain her generalized edema. Later on, her albiglutide was discontinued, which
      lead to the resolution of her edema. We conclude that her generalized edema could
      be due to a possible side effect of albiglutide.

PMID- 30116681
TI  - Enlarging Plexiform Tumor in a Pregnant Patient with Neurofibromatosis Type One.
AB  - Neurofibromatosis type one (NF1) is a relatively common genetic disorder,
      however, it is rare to see in pregnancy. There are few case reports detailing a
      link between increasing tumor size in pregnant patients with NF1 likely due to
      the increase in hormones. However, some neurofibromas, like the plexiform, can
      undergo malignant degeneration into aggressive malignant peripheral nerve sheath
      tumors (MPNST). Any patient with NF1 should undergo a prompt evaluation and
      biopsy of a plexiform neurofibroma if it starts to change in size or consistency.
      Due to the increased risk of malignancy in NF1 patients and the poor survival
      rates in MPNST, it should never be assumed that tumors enlarging in pregnancy are
      due to hormones. The case below details the enlargement of a plexiform
      neurofibroma on a 21-year-old gravida two parity one female at 28 weeks with NF1.

PMID- 30116682
TI  - Refractory Hypoglycemia and Seizures as the Initial Presenting Manifestation of
      Empty Sella Syndrome.
AB  - An empty sella is reported to occur in 5.5%-23.5% of the population and is
      usually asymptomatic. It can be associated with endocrine disturbances. We report
      a 48-year-old woman who presented with refractory hypoglycemia, seizures, and
      shock that improved with levothyroxine, hydrocortisone, and octreotide.
      Investigations revealed central hypothyroidism, hypoprolactinemia, low
      gonadotropins, normal C-peptide and a primary empty sella. Case reports of
      Sheehan syndrome with or without empty sella causing hypoglycemia have been
      reported occasionally. Our patient had never become pregnant. She had experienced
      premature menopause and symptoms suggestive of hypothyroidism for many years
      (without treatment) before her emergency department admission for altered
      sensorium.

PMID- 30116683
TI  - An Attempt to Quantitate "Value" In Medical Oncologic Therapy.
AB  - Objective We wanted to examine the incremental cost-effective ratio (ICER) for a
      variety of Food and Drug Administration (FDA) approved oncology drugs in the
      adjuvant or curative setting to determine the value provided. Design We examined
      the annualized incremental drug costs of a variety of FDA approved
      chemotherapeutic drugs used in an adjuvant or curative setting based on National
      Comprehensive Cancer Network (NCCN) category 1 practice guidelines for melanoma,
      Her2/neu over-expressive breast cancer, renal cell carcinoma, stage IIIA non
      small cell lung cancer, myeloma, B cell lymphoma, and Hodgkin lymphoma. The
      studies we examined were randomized clinical trials on which the NCCN guidelines
      are based; we solely examined the incremental cost-effectiveness of the trial
      drug as we assumed that the costs of the health care provided were equivalent
      between the two treatment arms. We used a formula to determine the incremental
      cost-effectiveness ratio (ICER). The ICER compares a new intervention (C new)
      with its alternate (C alt) divided by the quality-adjusted life-years (QALY) that
      results from the new intervention (QALY new) versus the alternate (QALY alt) and
      is expressed as ICER = (C new-C alt)/(QALY new-QALY alt). The QALY's were derived
      from what was reported in the study and based on the incremental disease-free
      survival. Results Drugs such as rituximab provide high value in the curative
      therapy for lymphoma. Drugs such as adjuvant dabrafenib and trametinib provide
      intermediate value in the treatment of melanoma, and similarly with maintenance
      lenalidomide in myeloma and adjuvant trastuzumab in breast cancer. Oncologic
      drugs that provide low value include adjuvant ipilimumab in melanoma, adjuvant
      sunitinib in renal cell carcinoma, adjuvant neratinib in breast cancer, adjuvant
      durvalumab in lung cancer, and brentuximab in the curative therapy for Hodgkin's
      lymphoma. Conclusion The ICER needs to be evaluated for newly approved FDA
      oncology chemotherapeutic drugs before incorporating them into routine clinical
      practice.

PMID- 30116684
TI  - Re-boot: Simulation Elective for Medical Students as Preparation Bootcamp for
      Obstetrics and Gynecology Residency.
AB  - OBJECTIVE: To evaluate the impact of a simulation-based elective on medical
      student preparedness for obstetrics and gynecology (OB/GYN) residency. METHODS: A
      two-week, simulation-based elective course for post-clerkship medical students
      was developed, and 10 students participated at a single academic institution in
      2016 and 2017. Using standardized patients and team-based training, students
      practiced procedural and surgical skills, as well as the diagnosis, management,
      and work-up of commonly seen problems. Close coaching with a low student-faculty
      ratio was employed for each session, allowing for individualized feedback in real
      time. Prior to and after completing the elective, student knowledge was evaluated
      using the Preparation for Residency Knowledge Assessment tool (PrepForRes).
      Written course evaluations were also completed by students at the end of the
      course. RESULTS: Mean scores on the PrepForRes exam increased from 63.6% to 75.3%
      (p=0.0136). Notably, the average post-course score improved to a passing level,
      and all but one student achieved a passing score on the post-course test. Course
      evaluations and student feedback showed high satisfaction rates with the course.
      CONCLUSIONS: This study demonstrates that a simulation-based elective course is
      an effective tool for helping medical students transition to OB/GYN residency. As
      medical schools work to facilitate the transition from undergraduate to graduate
      medical education, simulation can bridge gaps during this transition in order for
      students to meet entry-level residency requirements.

PMID- 30116685
TI  - Academic Life in Emergency Medicine Blog and Podcast Watch: Respiratory
      Emergencies.
AB  - The Academic Life in Emergency Medicine (ALiEM) Approved Instructional Resources
      (AIR) Series and Approved Instruction Resources Professional (AIR-Pro) Series
      were created in 2014 and 2015, respectively, to address the need for curation of
      online educational content as well as a nationally available curriculum that
      meets individualized interactive instruction criteria. These two programs
      identify high-quality educational blog and podcast content using an expert-based
      approach. We summarize the accredited posts on respiratory emergencies that met
      our a priori determined quality criteria per evaluation by eight experienced
      faculty educators in emergency medicine.

PMID- 30116686
TI  - Development of a Vacuum Electrospray Droplet Ion Gun for Secondary Ion Mass
      Spectrometry.
AB  - Atmospheric pressure electrospray had been used in previous studies to generate
      massive water droplet ion beams, and the beams successfully achieved efficient
      desorption/ionization of biomolecules, low damage etching of polymers and
      nonselective etching of metal oxides. However, this droplet ion beam was not
      practical as a primary ion beam for surface analysis instruments because it
      required differential pumping and lacked adequate beam current and density. To
      improve the beam performance, we have proposed to use vacuum electrospray of
      aqueous solutions as a beam source, and developed a technique for producing a
      stable electrospray of aqueous solution in vacuum. We also designed a prototype
      of a vacuum electrospray droplet ion gun, and measured the beam properties.
      Finally, the applicability of this ion gun in secondary ion mass spectrometry is
      discussed.

PMID- 30116687
TI  - Defect formation in multiwalled carbon nanotubes under low-energy He and Ne ion
      irradiation.
AB  - The mechanical, structural, electronic and magnetic properties of carbon
      nanotubes can be modified by electron or ion irradiation. In this work we used 25
      keV He+ and Ne+ ion irradiation to study the influence of fluence and sample
      thickness on the irradiation-induced damage of multiwalled carbon nanotubes
      (MWCNTs). The irradiated areas have been characterised by correlative Raman
      spectroscopy and TEM imaging. In order to preclude the Raman contribution coming
      from the amorphous carbon support of typical TEM grids, a new methodology
      involving Raman inactive Au TEM grids was developed. The experimental results
      have been compared to SDTRIMSP simulations. Due to the small thickness of the
      MWCNTs, sputtering has been observed for the top and bottom side of the samples.
      Depending on thickness and ion species, the sputter yield is significantly higher
      for the bottom than the top side. For He+ and Ne+ irradiation, damage formation
      evolves differently, with a change in the trend of the ratio of D to G peak in
      the Raman spectra being observed for He+ but not for Ne+. This can be attributed
      to differences in stopping power and sputter behaviour.

PMID- 30116689
TI  - Self-assembled quasi-hexagonal arrays of gold nanoparticles with small gaps for
      surface-enhanced Raman spectroscopy.
AB  - The fabrication and optical characterization of self-assembled arrangements of
      rough gold nanoparticles with a high area coverage and narrow gaps for surface
      enhanced Raman spectroscopy (SERS) are reported. A combination of micellar
      nanolithography and electroless deposition (ED) enables the tuning of the spacing
      and size of the noble metal nanoparticles. Long-range ordered quasi-hexagonal
      arrays of gold nanoparticles on silicon substrates with a variation of the
      particle sizes from about 20 nm to 120 nm are demonstrated. By increasing the
      particle sizes for the homogeneously spaced particles, a large number of narrow
      gaps is created, which together with the rough surface of the particles induces a
      high density of intense hotspots. This makes the surfaces interesting for future
      applications in near-field-enhanced bio-analytics of molecules. SERS was
      demonstrated by measuring Raman spectra of 4-MBA on the gold nanoparticles. It
      was verified that a smaller inter-particle distance leads to an increased SERS
      signal.

PMID- 30116688
TI  - Electromigrated electrical optical antennas for transducing electrons and photons
      at the nanoscale.
AB  - Background: Electrically controlled optical metal antennas are an emerging class
      of nanodevices enabling a bilateral transduction between electrons and photons.
      At the heart of the device is a tunnel junction that may either emit light upon
      injection of electrons or generate an electrical current when excited by a light
      wave. The current study explores a technological route for producing these
      functional units based upon the electromigration of metal constrictions. Results:
      We combine multiple nanofabrication steps to realize in-plane tunneling junctions
      made of two gold electrodes, separated by a sub-nanometer gap acting as the
      feedgap of an optical antenna. We electrically characterize the transport
      properties of the junctions in the light of the Fowler-Nordheim representation
      and the Simmons model for electron tunneling. We demonstrate light emission from
      the feedgap upon electron injection and show examples of how this nanoscale light
      source can be coupled to waveguiding structures. Conclusion: Electromigrated in
      plane tunneling optical antennas feature interesting properties with their unique
      functionality enabling interfacing electrons and photons at the atomic scale and
      with the same device. This technology may open new routes for device-to-device
      communication and for interconnecting an electronic control layer to a photonic
      architecture.

PMID- 30116690
TI  - Biomimetic and biodegradable cellulose acetate scaffolds loaded with
      dexamethasone for bone implants.
AB  - There is, as a matter of fact, an ever increasing number of patients requiring
      total hip replacement (Pabinger, C.; Geissler, A. Osteoarthritis
      Cartilage2014,22, 734-741). Implant-associated acute inflammations after an
      invasive orthopedic surgery are one of the major causes of implant failure. In
      addition, there are instability, aseptic loosening, infection, metallosis and
      fracture (Melvin, J. S.; Karthikeyan, T.; Cope, R.; Fehring, T. K. J.
      Arthroplasty2014,29, 1285-1288). In this work, a drug-delivery nanoplatform
      system consisting of polymeric celluloce acetate (CA) scaffolds loaded with
      dexamethasone was fabricated through electrospinning. Atomic force microscopy
      (AFM) and scanning electron microscopy (SEM) indicated the successful fabrication
      of these structures. Cytotoxicity studies were performed by using MTT assay,
      methylene-blue staining and SEM fixation and showed very good cell adhesion and
      proliferation, indicating the cytocompatibility of these fibrous scaffolds. Drug
      release kinetics was measured for the evaluation of a controllable and sustained
      release of anti-inflammatory drug onto the engineered implants and degradation
      study was conducted in order to assess the mass loss of polymers. This drug
      delivery nanoplatform as coating on titanium implants may be a promising approach
      not only to alleviate but also to prevent implant-associated acute inflammations
      along with a simultaneous controlled release of the drug.

PMID- 30116693
TI  - A variable probe pitch micro-Hall effect method.
AB  - Hall effect metrology is important for a detailed characterization of the
      electronic properties of new materials for nanoscale electronics. The micro-Hall
      effect (MHE) method, based on micro four-point probes, enables a fast
      characterization of ultrathin films with minimal sample preparation. Here, we
      study in detail how the analysis of raw measurement data affects the accuracy of
      extracted key sample parameters, i.e., how the standard deviation on sheet
      resistance, carrier mobility and Hall sheet carrier density is affected by the
      data analysis used. We compare two methods, based primarily on either the sheet
      resistance signals or the Hall resistance signals, by theoretically analysing the
      effects of electrode position errors and electrical noise on the standard
      deviations. We verify the findings with a set of experimental data measured on an
      ultrashallow junction silicon sample. We find that in presence of significant
      electrical noise, lower standard deviation is always obtained when the
      geometrical analysis is based on the sheet resistance signals. The situation is
      more complicated when electrode position errors are dominant; in that case, the
      better method depends on the experimental conditions, i.e., the distance between
      the insulating boundary and the electrodes. Improvement to the accuracy of Hall
      Effect measurement results is crucial for nanoscale metrology, since surface
      scattering often leads to low carrier mobility.

PMID- 30116692
TI  - Metal-free catalysis based on nitrogen-doped carbon nanomaterials: a
      photoelectron spectroscopy point of view.
AB  - In this review, we discuss the use of doped carbon nanomaterials in catalysis, a
      subject that is currently intensively studied. The availability of carbon
      nanotubes since the 1990's and of graphene ten years later prompted the
      development of novel nanotechnologies. We review this topic linking fundamental
      surface science to the field of catalysis giving a timely picture of the state of
      the art. The main scientific questions that material scientists have addressed in
      the last decades are described, in particular the enduring debate on the role of
      the different nitrogen functionalities in the catalytic activity of nitrogen
      doped carbon nanotubes and graphene.

PMID- 30116691
TI  - Recent highlights in nanoscale and mesoscale friction.
AB  - Friction is the oldest branch of non-equilibrium condensed matter physics and, at
      the same time, the least established at the fundamental level. A full
      understanding and control of friction is increasingly recognized to involve all
      relevant size and time scales. We review here some recent advances on the
      research focusing of nano- and mesoscale tribology phenomena. These advances are
      currently pursued in a multifaceted approach starting from the fundamental atomic
      scale friction and mechanical control of specific single-asperity combinations,
      e.g., nanoclusters on layered materials, then scaling up to the meso/microscale
      of extended, occasionally lubricated, interfaces and driven trapped optical
      systems, and eventually up to the macroscale. Currently, this "hot" research
      field is leading to new technological advances in the area of engineering and
      materials science.

PMID- 30116695
TI  - High-throughput synthesis of modified Fresnel zone plate arrays via ion beam
      lithography.
AB  - Fresnel zone plates (FZP) are diffractive photonic devices used for high
      resolution imaging and lithography at short wavelengths. Their fabrication
      requires nano-machining capabilities with exceptional precision and strict
      tolerances such as those enabled by modern lithography methods. In particular,
      ion beam lithography (IBL) is a noteworthy method thanks to its robust direct
      writing/milling capability. IBL allows for rapid prototyping of high-resolution
      FZPs that can be used for high-resolution imaging at soft X-ray energies. Here,
      we discuss improvements in the process enabling us to write zones down to 15 nm
      in width, achieving an effective outermost zone width of 30 nm. With a 35%
      reduction in process time and an increase in resolution by 26% compared to our
      previous results, we were able to resolve 21 nm features of a test sample using
      the FZP. The new process conditions are then applied for fabrication of large
      arrays of high-resolution zone plates. Results show that relatively large areas
      can be decorated with nanostructured devices via IBL by using multipurpose
      SEM/FIB instruments with potential applications in FEL focusing, extreme UV and
      soft X-ray lithography and as wavefront sensing devices for beam diagnostics.

PMID- 30116694
TI  - Fabrication of photothermally active poly(vinyl alcohol) films with gold
      nanostars for antibacterial applications.
AB  - The unique photothermal properties of non-spherical gold nanoparticles under near
      infrared (NIR) irradiation find broad application in nanotechnology and
      nanomedicine. The combination of their plasmonic features with widely used
      biocompatible poly(vinyl alcohol) (PVA) films can lead to novel hybrid polymeric
      materials with tunable photothermal properties and a wide range of applications.
      In this study, thin PVA films containing highly photothermally efficient gold
      nanostars (GNSs) were fabricated and their properties were studied. The resulting
      films displayed good mechanical properties and a pronounced photothermal effect
      under NIR irradiation. The local photothermal effect triggered by NIR irradiation
      of the PVA-GNS films is highly efficient at killing bacteria, therefore providing
      an opportunity to develop new types of protective antibacterial films and
      coatings.

PMID- 30116696
TI  - Nanoconjugates of a calixresorcinarene derivative with methoxy poly(ethylene
      glycol) fragments for drug encapsulation.
AB  - In order to obtain a non-toxic amphiphilic calixresorcinarene capable to form
      nanoconjugates for drug encapsulation, tetraundecylcalixresorcinarene
      functionalized by methoxy poly(ethylene glycol) chains has been synthesized. The
      macrocycle obtained is characterized by low hemotoxicity. In aqueous solution it
      forms nanoassociates that are able to encapsulate organic substrates of different
      hydrophobicity, including drugs (doxorubicin, naproxen, ibuprofen, quercetin).
      The micelles of the macrocycle slowed down the release of the hydrophilic
      substrates in vitro. In physiological sodium chloride solution and phosphate
      buffered saline, the micelles of the macrocycle acquire thermoresponsive
      properties and exhibit a temperature-controlled release of doxorubicin in vitro.
      The combination of the low toxicity and the encapsulation properties of the
      obtained calixresorcinarene-mPEG conjugate shows promising potential for the use
      as a supramolecular drug-delivery system.

PMID- 30116698
TI  - Changes in sedentary time are associated with changes in mental wellbeing over 1
      year in young adults.
AB  - Excessive sedentary time is related to poor mental health. However, much of the
      current literature uses cross-sectional data and/or self-reported sedentary time,
      and does not assess factors such as sedentary bout length. To address these
      limitations, the influence of objectively measured sedentary time including
      sedentary bout length (i.e. <30 min, >=30 min) on mood, stress, and sleep, was
      assessed in 271 healthy adults (49% women; age 27.8 +/- 3.7) across a 1-year
      period between 2011 and 2013 in Columbia, SC. Participants completed the Profile
      of Mood States and the Perceived Stress Scale, and wore a Sensewear Armband to
      assess sedentary time, physical activity, and sleep for ten days at baseline and
      one year. A series of fixed-effects regressions was used to determine the
      influence of both baseline levels and changes in daily sedentary time (total and
      in bouts) and physical activity on changes in mood, stress, and sleep over one
      year. Results showed that across the year, decreases in total sedentary time, and
      time in both short and long bouts, were associated with improvements in mood,
      stress and sleep (p < 0.05). Increases in physical activity were only
      significantly predictive of increases in sleep duration (p < 0.05). Thus,
      reductions in sedentary time, regardless of bout length, positively influenced
      mental wellbeing. Specifically, these results suggest that decreasing daily
      sedentary time by 60 min may significantly attenuate the negative effects of high
      levels of pre-existing sedentary time on mental wellbeing. Interventions
      manipulating sedentary behavior are needed to determine a causal link with
      wellbeing and further inform recommendations.

PMID- 30116699
TI  - The association between objective measures of residence and worksite neighborhood
      environment, and self-reported leisure-time physical activities: The Aichi
      Workers' Cohort Study.
AB  - The possible effects of a neighborhood's built environment on physical activity
      have not been studied in Asian countries as much as in Western countries. The
      present study cross-sectionally examined the relationship between geographic
      information system (GIS) measured residence and worksite neighborhood
      walkability, and the number of parks/green spaces and sports facilities within a
      1 km radius of home and workplace, with self-reported leisure-time habitual (3-4
      times per week or more) walking and moderate-to-vigorous intensity habitual
      exercise among local government workers aged 18 to 64 years living in an urban
      suburban area of Aichi, Japan in 2013. A single-level binomial regression model
      was used to estimate the multivariable odds ratios (ORs) and 95% confidence
      intervals (95% CIs). Of the 1959 male and 884 female participants, 288 (15%) and
      141 (16%) reported habitual walking, respectively, and 18% and 17% reported
      habitual exercise, respectively. Compared with women who resided in neighborhood
      with a walkability index of 4-30, those living in an area with that of 35-40 were
      significantly more likely to engage in leisure-time habitual exercise
      (multivariable OR: 1.70, 95% CI: 1.08-2.68). Marginally significant positive
      associations were found between leisure-time habitual exercise and the
      residential neighborhood's number of parks/green spaces among women, as well as
      the number of sports facilities among men. In conclusion, a residential
      neighborhood environment characterized by higher walkability may contribute to
      the initiation or maintenance of moderate-to-vigorous intensity leisure-time
      exercise among working women living in an urban-suburban area of Japan.

PMID- 30116700
TI  - Retrospective reports of former smokers: Receiving doctor's advice to quit
      smoking and using behavioral interventions for smoking cessation in the United
      States.
AB  - The study investigated the over-time changes and racial/ethnic disparities in the
      quality of health care services for cigarette smoking cessation in the U.S. from
      2007 to 2015. The primary measures included receiving a doctor's advice to quit
      smoking in the year before smoking cessation and using behavioral interventions
      for smoking cessation (telephone helplines and web-based interventions) while
      trying to quit smoking. The study was conducted from January to July 2018. We
      used merged data from the 2010-11 and 2014-15 Tobacco Use Supplement to the
      Current Population Survey. The sample sizes were 7011 and 12,025, respectively,
      for the analyses corresponding to two primary measures. The rate of receiving a
      doctor's advice to quit increased significantly from 66% (SE = 2%) in 2007 to 73%
      (SE = 4%) in 2015. The rate of usage of telephone helplines or web-based
      interventions for smoking cessation increased only from 3% (SE = 1%) in 2007 to
      5% (SE = 1%) in 2015. These positive trends remained even after adjusting for
      several important factors. For both measures, the rates were consistently lower
      among Hispanic smokers than Non-Hispanic Black/African American and White
      smokers. Despite the availability of states' behavioral interventions for
      cessation of tobacco use, utilization of these interventions remains very low,
      indicating that smokers may not be aware of these free resources, may have
      misconceptions about these interventions being evidence-based, or there are
      barriers for using these interventions.

PMID- 30116697
TI  - An Update on the Global Epidemiology of Syphilis.
AB  - Purpose of Review: Syphilis continues to cause morbidity and mortality worldwide.
      While syphilis infection is easily identifiable and treatable, rates of syphilis
      infection continue to increase among select populations in high-income countries
      and remain at endemic levels in low- and middle-income counties. Recent findings:
      World Health Organization recommended strategies have led to the dual elimination
      of mother-to-child transmission of syphilis and HIV in several countries, however
      outbreaks among select populations need to be adequately addressed. Summary:
      Continued vigilance and investment is needed to address syphilis worldwide. The
      epidemiology of syphilis differs in high-income and low- and middle-income
      counties.

PMID- 30116701
TI  - Medicaid coverage accuracy in electronic health records.
AB  - Health insurance coverage facilitates access to preventive screenings and other
      essential health care services, and is linked to improved health outcomes;
      therefore, it is critical to understand how well coverage information is
      documented in the electronic health record (EHR) and which characteristics are
      associated with accurate documentation. Our objective was to evaluate the
      validity of EHR data for monitoring longitudinal Medicaid coverage and assess
      variation by patient demographics, visit types, and clinic characteristics. We
      conducted a retrospective, observational study comparing Medicaid status
      agreement between Oregon community health center EHR data linked at the patient
      level to Medicaid enrollment data (gold standard). We included adult patients
      with a Medicaid identification number and >=1 clinic visit between 1/1/2013
      12/31/2014 [>1 million visits (n = 135,514 patients)]. We estimated statistical
      correspondence between EHR and Medicaid data at each visit (visit-level) and for
      different insurance cohorts over time (patient-level). Data were collected in
      2016 and analyzed 2017-2018. We observed excellent agreement between EHR and
      Medicaid data for health insurance information: kappa (>0.80), sensitivity
      (>0.80), and specificity (>0.85). Several characteristics were associated with
      agreement; at the visit-level, agreement was lower for patients who preferred a
      non-English language and for visits missing income information. At the patient
      level, agreement was lower for black patients and higher for older patients seen
      in primary care community health centers. Community health center EHR data are a
      valid source of Medicaid coverage information. Agreement varied with several
      characteristics, something researchers and clinic staff should consider when
      using health insurance information from EHR data.

PMID- 30116703
TI  - Accumulation of unhealthy behaviors: Marked social inequalities in men and women.
AB  - The objective of this study was to compare the accumulation of unhealthy
      behaviors at the bottom of the social scale in men and women and, secondarily, to
      compare social and gender-based inequalities. Fifty-two general practitioners
      from the Paris area volunteered to participate. A sample of 70 patients
      (stratified by gender) aged 40-74 years was randomly chosen from each physician's
      patient panel and asked to complete a questionnaire about their social position
      and health behaviors: tobacco and alcohol use, unhealthy diet, and physical
      inactivity. Mixed Poisson models were used to describe, with relative risks (RRs)
      and relative inequality indexes (RIIs), the social inequalities in the
      accumulation of these four unhealthy behaviors. In 2008-2009, 71% of the 3640
      patients returned their questionnaires. Men had an average of 1.59 of the 4
      unhealthy behaviors we studied, and women 1.35 (RR = 1.18; 95% CI [1.11-1.25]).
      The mean number of unhealthy behaviors increased significantly for both genders
      from the top to the bottom of the social scale. The order of magnitude of RIIs
      was similar among men and women, ranging from 1.33 (occupational RII among women,
      95% CI [1.11-1.60]) through 1.69 (financial RII among women, 95% CI [1.43-1.99]).
      None of the interaction tests between gender and social position was significant.
      The social inequalities had significantly wider amplitudes than those between
      genders for two of the three indicators of social position. The amplitude of
      social gradients related to unhealthy behaviors was similar between men and women
      and exceeded the gender inequality between them.

PMID- 30116704
TI  - The fecal immunochemical test (fit): Selected aspects regarding its effectiveness
      for colorectal cancer screening in Quebec City.
AB  - Background and aims: FIT's value has been ascertained across Canada and
      worldwide, but still needs to be assessed within the province of Quebec. There
      also remains a gap between formal indications for FIT, and its actual use in
      clinical practice. This research aims to evaluate some aspects of FIT's
      effectiveness in our setting, and its application by prescribers. Methods: We
      retrospectively identified and reviewed all the colonoscopies conducted for a
      positive FIT in 2014 at 2 hospitals located in Quebec City. Results: Five hundred
      and fifty-nine (559) colonoscopies were reviewed. We obtained PPVs of 6.8% and
      46.9% for the detection of CRC and AA, respectively. The PPV for the detection of
      SCL was higher in men compared to women (OR 1.56, 95%CI 1.11-2.20) and among
      justified FITs compared to unwarranted ones (OR 1.88, 95%CI 1.34-2.63). The PPV
      for CRC detection was 25.0% in the presence of unexplained iron deficiency anemia
      and 6.5% when anemia was absent (p = 0.0058). In 49.9% of cases, the prescription
      of a FIT was inappropriate. Conclusion: The FIT holds a better PPV for detecting
      SCL among men and when it is indicated. Anemia is associated with a higher CRC
      detection rate. Half of the FITs were not initially indicated.

PMID- 30116702
TI  - Daily Minutes of Unprotected Sun Exposure (MUSE) Inventory: Measure description
      and comparisons to UVR sensor and sun protection survey data.
AB  - One in five US adults will be diagnosed with skin cancer. As most skin cancers
      are attributable to sun exposure, this risk factor is an important target for
      research and intervention. Most sun exposure measures assess frequency of
      specific sun-protection behaviors, which does not account for the use of
      multiple, potentially overlapping sun-protection methods. In contrast, the Daily
      Minutes of Unprotected Sun Exposure (MUSE) Inventory assesses sun-protection
      behavior during self-reported activities, providing several useful metrics,
      including duration of unprotected sun exposure on 17 body sites, combined to
      yield an overall MUSE score weighted by percent of body exposed. The present
      study was conducted July-September 2017, in Chicago, IL USA. For 10 days,
      participants (39 melanoma survivors; Mage = 58.59, 64.5% female) wore an
      ultraviolet radiation (UVR) sensor and completed the Daily MUSE Inventory each
      evening. The Sun Habits Survey was completed at the end of the study. Outdoor
      time reported in the MUSE Inventory significantly predicted outdoor time recorded
      by UVR sensors, B = 0.53, p < .001. For all sun-protection behaviors except
      shade, reports from the Daily MUSE Inventory (i.e., percentage of outdoor time a
      particular strategy was used) correlated with frequency ratings of the same
      strategy from the Sun Habits Survey (rs = 0.66-0.75, p < .05). In sum, the Daily
      MUSE Inventory corresponds with sensor and survey data, and provides a novel
      metric of unprotected sun exposure that will be useful for evaluating overall
      extent of sun exposure, including exposure on several smaller body sites that are
      at high risk for skin cancer.

PMID- 30116705
TI  - Weight loss expectations and determinants in a large community-based sample.
AB  - While weight-loss expectations have primarily been studied in people enrolled in
      weight-loss programs, the present study explores patient expectations about
      weight-loss and identifies related determinants in a large, non-clinical
      population. 3916 volunteers (age > 18 years) participated in 2012 in a community
      based survey in the French-speaking region of Belgium. Participants were asked to
      define "dream", "goal", "happy", "acceptable", and "disappointed" weights. Other
      self-reported measures were used to determine each participant's body mass index
      (BMI), body image discrepancy (BID), subjective norm (SN), weight loss activity,
      weight history, quality of life (QoL), and demographic and socioeconomic
      characteristics. The study focused on the determinants of unrealistic weight-loss
      "goal" (>=10% of initial weight). Results showed median weight loss targets
      ranged from 5 kg ("disappointed" weight loss) to 21 kg ("dreamed" weight loss).
      Respondents considered the recommended weight-loss target (5-10%) disappointing.
      Severe and morbid obesity categories are at high risk of unrealistic weight loss
      goal. Unrealistic weight-loss goals was associated with female gender, weight
      loss activity, overweight history and lower QoL in overweight and moderate
      obesity respondents. These findings confirm the urgent need to help patients
      accept more modest weight loss outcomes and the need for personalized care that
      considers the patient's specific profile and both weight loss expectations and
      determinants.

PMID- 30116706
TI  - S-factor of 14N(alpha,gamma)18F reaction at low-energies.
AB  - The astrophysical S-factor of the 14N(alpha,gamma)18F reaction has been studied
      at range of bombarding energy 1-1.30 MeV. The 14N(alpha,gamma)18F process is
      important in low energy astrophysics so that a possible source of energy in
      massive stars which have spent their hydrogen cycle. Using the Wood-saxon
      potential model, we have been calculated non resonances the astrophysical S
      factors for the E2 transition and our results for Ealpha=0.0  MeV is S~0.5  MeV.b
      where from experimental is measured to Ealpha=0.0 is S~o.7  MeV.b (Couch et al.,
      1971) that in comparison with our data good agreement is achieved for the
      astrophysical S-factor of this process.

PMID- 30116707
TI  - Cavotricuspid isthmus ablation using multimodality imaging in Ebstein anomaly
      with a mechanical tricuspid valve replacement.

PMID- 30116708
TI  - Long-term follow-up of permanent atrial standstill in a German family with
      mutation in the SCN5A gene.

PMID- 30116709
TI  - Posterior cardiac compression from a large hiatal hernia-A novel cause of
      ventricular tachycardia.

PMID- 30116710
TI  - Successful ventricular tachycardia ablation in a patient with a biventricular
      ventricular assist device and heparin-induced thrombocytopenia using bivalirudin.

PMID- 30116711
TI  - Successful ablation of premature ventricular contractions originating from the
      inferoseptal process of the left ventricle using a coronary sinus approach.

PMID- 30116712
TI  - Intravenous sotalol for the management of postoperative junctional ectopic
      tachycardia.

PMID- 30116713
TI  - Bundle branch reentry with His dissociation-The His bundle: Bystander or
      participant?

PMID- 30116714
TI  - Talaromyces (Penicillium) marneffei infection.
AB  - A 41-year-old man from the emergency department presented with fever for 2 weeks,
      sore throat, dry cough and generalized umbilicated skin lesions (face (Fig. 1),
      and chest (Fig. 2)). HIV antibody was positive, CD4+ count was 2/MUL. His skin
      swab, sputum and blood culture all yielded Talaromyces (Penicillium) marneffei
      (Fig. 3). Talaromyces marneffei is an important cause of morbidity and mortality
      in HIV-infected and other immunosuppressed patients who live in or are from
      endemic areas especially Southeast Asia. Amphotericin B or Itraconazole should be
      initiated as soon as possible for patients with talaromycosis.

PMID- 30116716
TI  - Laparoscopic approach for retrocaval ureter: How to decrease surgical time?

PMID- 30116715
TI  - Idiopathic chronic hematocele mimicking a mesothelioma of the tunica vaginalis
      testis.

PMID- 30116717
TI  - Atypical calcified paraganglioma of the urinary bladder: A new case report.

PMID- 30116718
TI  - Testicular torsion in older men: It must always be considered.

PMID- 30116719
TI  - Adrenal hemorrhagic pseudocyst - A case report of a rare presentation of
      pheochromocytoma.

PMID- 30116720
TI  - Investigation of a renal mass: Diagnosing renal paraganglioma.

PMID- 30116723
TI  - 3D electron tomographic and biochemical analysis of ER, Golgi and trans Golgi
      network membrane systems in stimulated Venus flytrap (Dionaea muscipula)
      glandular cells.
AB  - Background: The insect-trapping leaves of Dionaea muscipula provide a model for
      studying the secretory pathway of an inducible plant secretory system. The leaf
      glands were induced with bovine serum albumin to secrete proteases that were
      characterized via zymogram activity gels over a 6-day period. The accompanying
      morphological changes of the endoplasmic reticulum (ER) and Golgi were analyzed
      using 3D electron tomography of glands preserved by high-pressure freezing/freeze
      substitution methods. Results: Secretion of multiple cysteine and aspartic
      proteases occurred biphasically. The majority of the Golgi was organized in
      clusters consisting of 3-6 stacks surrounded by a cage-like system of ER
      cisternae. In these clusters, all Golgi stacks were oriented with their cis-most
      C1 cisterna facing an ER export site. The C1 Golgi cisternae varied in size and
      shape consistent with the hypothesis that they form de novo. Following induction,
      the number of ER-bound polysomes doubled, but no increase in COPII vesicles was
      observed. Golgi changes included a reduction in the number of cisternae per stack
      and a doubling of cisternal volume without increased surface area. Polysaccharide
      molecules that form the sticky slime cause swelling of the trans and trans Golgi
      network (TGN) cisternae. Peeling of the trans-most cisternae gives rise to free
      TGN cisternae. One day after gland stimulation, the free TGNs were frequently
      associated with loose groups of oriented actin-like filaments which were not seen
      in any other samples. Conclusions: These findings suggest that the secretory
      apparatus of resting gland cells is "overbuilt" to enable the cells to rapidly up
      regulate lytic enzyme production and secretion in response to prey trapping.

PMID- 30116722
TI  - Smurfs in Protein Homeostasis, Signaling, and Cancer.
AB  - Protein ubiquitination is an evolutionary conserved highly-orchestrated enzymatic
      cascade essential for normal cellular functions and homeostasis maintenance. This
      pathway relies on a defined set of cellular enzymes, among them, substrate
      specific E3 ubiquitin ligases (E3s). These ligases are the most critical players,
      as they define the spatiotemporal nature of ubiquitination and confer specificity
      to this cascade. Smurf1 and Smurf2 (Smurfs) are the C2-WW-HECT-domain E3
      ubiquitin ligases, which recently emerged as important determinants of pivotal
      cellular processes. These processes include cell proliferation and
      differentiation, chromatin organization and dynamics, DNA damage response and
      genomic integrity maintenance, gene expression, cell stemness, migration, and
      invasion. All these processes are intimately connected and profoundly altered in
      cancer. Initially, Smurf proteins were identified as negative regulators of the
      bone morphogenetic protein (BMP) and the transforming growth factor beta (TGF
      beta) signaling pathways. However, recent studies have extended the scope of
      Smurfs' biological functions beyond the BMP/TGF-beta signaling regulation. Here,
      we provide a critical literature overview and updates on the regulatory roles of
      Smurfs in molecular and cell biology, with an emphasis on cancer. We also
      highlight the studies demonstrating the impact of Smurf proteins on tumor cell
      sensitivity to anticancer therapies. Further in-depth analyses of Smurfs'
      biological functions and influences on molecular pathways could provide novel
      therapeutic targets and paradigms for cancer diagnosis and treatment.

PMID- 30116721
TI  - Epstein-Barr Virus-Associated Malignancies: Roles of Viral Oncoproteins in
      Carcinogenesis.
AB  - The Epstein-Barr virus (EBV) is the first herpesvirus identified to be associated
      with human cancers known to infect the majority of the world population. EBV
      associated malignancies are associated with a latent form of infection, and
      several of the EBV-encoded latent proteins are known to mediate cellular
      transformation. These include six nuclear antigens and three latent membrane
      proteins (LMPs). In lymphoid and epithelial tumors, viral latent gene expressions
      have distinct pattern. In both primary and metastatic tumors, the constant
      expression of latent membrane protein 2A (LMP2A) at the RNA level suggests that
      this protein is the key player in the EBV-associated tumorigenesis. While LMP2A
      contributing to the malignant transformation possibly by cooperating with the
      aberrant host genome. This can be done in part by dysregulating signaling
      pathways at multiple points, notably in the cell cycle and apoptotic pathways.
      Recent studies also have confirmed that LMP1 and LMP2 contribute to carcinoma
      progression and that this may reflect the combined effects of these proteins on
      activation of multiple signaling pathways. This review article aims to
      investigate the aforementioned EBV-encoded proteins that reveal established roles
      in tumor formation, with a greater emphasis on the oncogenic LMPs (LMP1 and
      LMP2A) and their roles in dysregulating signaling pathways. It also aims to
      provide a quick look on the six members of the EBV nuclear antigens and their
      roles in dysregulating apoptosis.

PMID- 30116724
TI  - Macrophage Phagocytosis and Allergen Avoidance in Children With Asthma.
AB  - Background and Objective: Airway macrophages perform the crucial functions of
      presenting antigens, clearing pathogens, and apoptotic cells. Macrophage
      phagocytosis is increased in adults with mild asthma and allergen exposure is
      known to activate macrophages. However, it is not clear whether the mechanism
      behind this is due to a primary defect or environmental factors such as allergen
      or lipopolysaccaride (LPS) exposure. Our aim was to assess the phagocytic
      function of airway macrophages in children with mild to moderate asthma after
      residence in a low allergen?LPS environment at high altitude. Methods: Sputum
      induction was performed in children with asthma at baseline and after residence
      for a 3 weeks' period at a high-altitude asthma center that has very low ambient
      allergen levels. The markers of eosinophilic inflammation (including percentage
      of macrophage cytoplasm with red hue) and phagocytosis of fluorescein
      isothiocyanate-labeled, heat-killed Staphylococcus aureus by airway macrophages
      was analyzed. Internalized bacteria were quantified using confocal microscopy.
      Results: The median bacterial count [mean (standard deviation)] per macrophage
      was significantly lower [39.55 (4.51) vs. 73.26 (39.42) (p = 0.006)] after
      residence at high altitude. No association was observed between markers of
      eosinophilic inflammation and bacterial phagocytosis. Conclusions: The results
      suggest that the mechanism behind the enhanced phagocytosis of bacteria in
      childhood asthma may be secondary to allergen or possibly LPS exposure.

PMID- 30116725
TI  - Optimizing Enteral Nutrition for Growth in Pediatric Chronic Kidney Disease
      (CKD).
AB  - Growth in pediatric Chronic Kidney Disease is important for long-term outcomes
      including final adult height and cognitive function. However, there are many
      barriers for children with chronic kidney disease to achieve adequate nutritional
      intake to optimize growth. This review highlights these unique concerns,
      including route of nutrition, dialysis contributions and biochemical indices.
      Fitting the enteral feeding to the patients' needs involves choosing an
      appropriate product or products, limiting harmful nutrients in excess, notably
      aluminum, and altering for electrolyte and micronutrient needs. Unique
      adjustments to the enteral regimen include accommodating volume needs, optimizing
      macronutrient ratios, specific electrolyte adjustments, the blending of products
      together, and adjustments made to consider patient and family psychosocial needs.
      When a holistic approach to medical nutrition therapy is applied, taking the
      above factors into consideration, adequate intake for growth of the child with
      CKD is achievable.

PMID- 30116726
TI  - Antibiotic Resistance in Syria: A Local Problem Turns Into a Global Threat.
AB  - Pharmaceutical sector of Syrian Arab Republic before the war was characterized by
      bold and successful development since the late 1980s. With the beginning of war
      in the country back in March 2011, momentum has changed significantly.
      Traumatism, communicable diseases related to morbidity and mortality as well as
      wound infections became particularly hot public health concern. This relates not
      only to the direct victims of military conflict but also to the displaced
      civilians, refugees, and ordinary citizens alike. Evolving legislative framework
      in Syria since 1980s tolerated dispensing of antibiotics without appropriate
      prescription. Such practice led to spreading of antibiotic resistance among the
      local bacteria frequently causing both community-acquired and nosocomial
      infections. Laboratory findings of resistant bacteria strains among the Syrian
      refugees in some European countries serve as evidence of concern spreading far
      beyond Middle East. Practice of self-diagnosis and self-medication with
      antibiotics by patients themselves and restraint to pharmacist advice is
      widespread. A number of recommendations is presented to stakeholders to compact
      antibiotic resistance after the peace is established in the country. The
      successful implementation of such recommendations is the way to preserve
      shrinking golden reserve of highly potent antibiotics as it is the last defense
      line against resistant bacterial strains causing severe life-threatening
      infections.

PMID- 30116727
TI  - Survivin Measurement improves Clinical Prediction of Transition From Arthralgia
      to RA-Biomarkers to Improve Clinical Sensitivity of Transition From Arthralgia to
      RA.
AB  - Background: Arthralgia often predates development of rheumatoid arthritis (RA). A
      set of joint symptoms commonly found in patients during their transition from
      arthralgia to RA, has been recently proposed. Aim: To combine clinical and
      serological markers and to improve recognition of imminent rheumatoid arthritis
      (RA) among patients with arthralgia. Methods: The total of 1,743 first-visit
      patients attending the rheumatology ward in Gothenburg for joint symptoms were
      identified during 12 consecutive months. Among those, 63 patients were classified
      as RA, 73 had undifferentiated arthritis and 180 had unexplained arthralgia. New
      RA cases, which prospectively developed during 48 months, comprised the
      preclinical (pre) RA group. The joint symptoms of the first-visit were analyzed
      aiming to distinguish patients with arthralgia and arthritis, and patients with
      pre-RA, who later developed the disease. The receiver operating characteristics
      curves were constructed. In the model, symptoms with the odds ratio >2.0 between
      the arthralgia and pre-RA were combined with information about RA-specific
      antibodies, C-reactive protein (CRP), and survivin in serum. Results: The
      proposed set of clinical symptoms distinguished the arthralgia patients from RA
      and pre-RA. Presence of survivin in serum showed strong association with clinical
      joint symptoms in arthralgia. A combination of symptoms in several small joint
      areas, increasing number of joints with symptoms, and patient's experience of
      swelling in small hand joints at the first visit identified pre-RA cases with 93%
      specificity. Grouping those symptoms with information about survivin, RA-specific
      antibodies, and CRP (or gender) in the final algorithm achieved 91% specificity
      and 55.2% of positive prediction for transition from arthralgia to RA.
      Conclusion: Clinical and serological parameters in combination aid recognition of
      imminent RA among arthralgia patients with appropriate sensitivity.

PMID- 30116728
TI  - Combination of Cloxacillin and Essential Oil of Melaleuca armillaris as an
      Alternative Against Staphylococcus aureus.
AB  - The emergence of resistance to antibiotics has been favored by abuse in the
      application of antimicrobials in human and animal medicine. Essential oils are a
      great resource to deal with this crisis. Melaleuca armillaris belongs to the
      family of Myrtaceae, rich in species with essential oils. Plant extracts has
      shown antimicrobial activity in many investigations. Cloxacillin (CLOX) is an
      antibiotic widely used in veterinary medicine against Staphylococcus aureus. Our
      aim was to assess pharmacodynamic interaction established by combining essential
      oil of M. armillaris (EO) with CLOX in search of a synergistic effect that
      maximizes the antibacterial activity against S. aureus. The EO was obtained by
      steam distillation and its composition was analyzed by a GC-FID-MS. The most
      abundant components in the EO were 1.8 cineole (72.3%), limonene (7.8%). and
      alpha-pinene (6%). We worked with wild type S. aureus strains (n = 3) isolated
      from Holstein cows, and S. aureus ATCC 29213 as the reference strain. The Minimum
      Inhibitory Concentration (MIC) of CLOX, EO and the combination was determined by
      microdilution in broth at pH 7.4; 6.5 and 5.0. The checkerboard method was
      applied to evaluate the interaction between CLOX and EO. The Fractional
      Inhibitory Concentration index (FIC) was established. From those combinations
      that yielded the lowest FIC values, we evaluated the index of antibacterial
      activity (E), established as the difference between the Log10 values of the
      number of viable bacteria at the initial (nt0) and at the end of the test (nt24).
      So, time-killing curves with CLOX and EO/CLOX combination at 0.5, 1, 2, 4, and 8
      fold the MIC in broth at pH 7.4; 6.5 and 5.0 were prepared. We considered
      Bacteriostatic effect (E = 0) Bactericidal effect (E = -3) and Effect of virtual
      eradication of bacteria (E = -4). A clear synergic activity between the EO and
      the CLOX was demonstrated, which allows reducing the MIC of beta-lactam against
      S. aureus. This interaction was favored by acidification of the medium, where
      lower concentrations of CLOX achieved a bactericidal effect, close to virtual
      eradication, in the presence of small amounts of EO.

PMID- 30116730
TI  - Detecting Differentially Variable MicroRNAs via Model-Based Clustering.
AB  - Identifying differentially variable (DV) genomic probes is becoming a new
      approach to detect novel genomic risk factors for complex human diseases. The F
      test is the standard equal-variance test in statistics. For high-throughput
      genomic data, the probe-wise F test has been successfully used to detect
      biologically relevant DNA methylation marks that have different variances between
      two groups of subjects (e.g., cases versus controls). In addition to DNA
      methylation, microRNA (miRNA) is another important mechanism of epigenetics.
      However, to the best of our knowledge, no studies have identified DV miRNAs. In
      this article, we proposed a novel model-based clustering method to improve the
      power of the probe-wise F test to detect DV miRNAs. We imposed special structures
      on covariance matrices for each cluster of miRNAs based on the prior information
      about the relationship between variances in cases and controls and about the
      independence among them. Simulation studies showed that the proposed method seems
      promising in detecting DV probes. Based on two real datasets about human
      hepatocellular carcinoma (HCC), we identified 7 DV-only miRNAs (hsa-miR-1826, hsa
      miR-191, hsa-miR-194-star, hsa-miR-222, hsa-miR-502-3p, hsa-miR-93, and hsa-miR
      99b) using the proposed method, one (hsa-miR-1826) of which has not yet been
      reported to be related to HCC in the literature.

PMID- 30116731
TI  - Discovery of Novel Caeridins from the Skin Secretion of the Australian White's
      Tree Frog, Litoria caerulea.
AB  - Abundant biologically active peptides have been discovered from frog skin
      secretions, a rich natural source of bioactive compounds with great potential in
      drug discovery. In this study, three Caeridin peptides, namely, Caeridin-1, S5
      Caeridin-1, and Caeridin-a1, were discovered from the skin secretion of the
      Australian White's tree frog, Litoria caerulea, for the first time, by means of
      combining transcriptomic and peptidomic analyses. It also represents the first
      report on bioactive Caeridins since this family of peptides was initially studied
      20 years ago. Chemically synthetic versions of each natural Caeridin demonstrated
      promising bioactivities either on rat smooth muscles or against microbial growth.
      Specifically, Caeridin-1 produced contraction of rat bladder smooth muscle, while
      S5-Caeridin-1 induced relaxation of rat ileum smooth muscle, both at nanomolar
      concentrations. Moreover, Caeridin-a1 was shown to potently inhibit the growth of
      the planktonic Gram-positive bacteria Staphylococcus aureus (S. aureus),
      methicillin-resistant S. aureus (MRSA), and Enterococcus faecalis (E. faecalis),
      the Gram-negative bacterium, Escherichia coli (E. coli), and the yeast, Candida
      albicans (C. albicans). The discovery of these Caeridins may induce further
      intensive and systematic studies of frog skin peptides to promote the discovery
      of natural templates as lead compounds for drug discovery and therapeutic
      application.

PMID- 30116733
TI  - The Impact of Type 2 Diabetes Mellitus on Long-Term Prognosis in Patients of
      Different Ages with Myocardial Infarction.
AB  - The objective of the study was to assess the impact of DM2 at baseline on long
      term mortality after acute myocardial infarction (MI) among different age groups.
      The data were taken from: "Register of Acute Myocardial Infarction." A total of
      862 patients were followed for five years after acute myocardial infarction. The
      primary endpoint was death from any cause. The patients were categorized into 2
      groups based on their ages: group 1-comprised patients older than working age (n
      = 358) and group 2-comprised employable patients (n = 504). A total of 208
      patients were diagnosed with both cardiovascular disease and DM2. Elderly
      patients with DM2 had worse prognosis and increased five-year mortality compared
      with patients of the same age group without DM2. Statistically significant
      differences in long-term outcomes were found in adult patients (p = 0.004) only
      in group with longer duration of diabetes, unlike the group with DM2 onset. In
      conclusion, Type 2 DM increased 5-year mortality rate of elderly patients with
      myocardial infarction. However, younger patients with both myocardial infarction
      and DM2 had more complications in the early post-MI period compared with patients
      of the same age group without DM2 but did not show any statistically significant
      differences in the long-term outcome.

PMID- 30116729
TI  - Exploring Long Noncoding RNAs in Glioblastoma: Regulatory Mechanisms and Clinical
      Potentials.
AB  - Gliomas are primary brain tumors presumably derived from glial cells. The WHO
      grade IV glioblastoma (GBM), characterized by rapid cell proliferation, easily
      recrudescent, high morbidity, and mortality, is the most common, devastating, and
      lethal gliomas. Molecular mechanisms underlying the pathogenesis and progression
      of GBMs with potential diagnostic and therapeutic value have been explored
      industriously. With the advent of high-throughput technologies, numerous long
      noncoding RNAs (lncRNAs) aberrantly expressed in GBMs were discovered recently,
      some of them probably involved in GBM initiation, malignant progression, relapse
      and resistant to therapy, or showing diagnostic and prognostic value. In this
      review, we summarized the profile of lncRNAs that has been extensively
      investigated in glioma research, with a focus on their regulatory mechanisms.
      Then, their diagnostic, prognostic, and therapeutic implications were also
      discussed.

PMID- 30116735
TI  - Erratum to "Meprin Metalloprotease Deficiency Associated with Higher Mortality
      Rates and More Severe Diabetic Kidney Injury in Mice with STZ-Induced Type 1
      Diabetes".
AB  - [This corrects the article DOI: 10.1155/2017/9035038.].

PMID- 30116734
TI  - Association of Autoimmune Thyroid Disease with Anti-GAD Antibody ELISA Test
      Positivity and Risk for Insulin Deficiency in Slowly Progressive Type 1 Diabetes.
AB  - The presence of antiglutamic acid decarboxylase antibody (GADA) is required for
      the diagnosis of slowly progressive type 1 diabetes (SPT1D). We examined the
      factors influencing GADA determination by radioimmunoassay (GADA-RIA) and by
      enzyme-linked immunosorbent assay (GADA-ELISA). Sixty patients with SPT1D and 154
      patients with type 2 diabetes were examined by both GADA-RIA and GADA-ELISA and
      for the presence of autoimmune thyroid disease (AITD). We compared the clinical
      characteristics of these patients based on the positivity or negativity of GADA
      RIA and GADA-ELISA, and the existence or nonexistence of AITD. Thirty of 60
      (50.0%) GADA-RIA-positive patients were GADA-ELISA negative, whereas none of the
      154 GADA-RIA-negative patients were GADA-ELISA positive. Concomitant AITD was
      significantly less in patients with GADA-RIA and without GADA-ELISA and was
      significantly more in patients with GADA-RIA and GADA-ELISA. In GADA-RIA-positive
      patients, there was no significant difference in the GADA-RIA titer among the
      GADA-ELISA-negative patients with and without AITD, and the GADA-ELISA-positive
      patients without AITD; whereas the frequency of insulin deficiency was
      significantly higher in the patients with AITD and/or GADA-ELISA than in those
      without AITD and GADA-ELISA. Examination of GADA-ELISA and AITD in GADA-RIA
      positive patients might be useful in predicting insulin deficiency in these
      patients.

PMID- 30116732
TI  - Factors Affecting the Absorption of Subcutaneously Administered Insulin: Effect
      on Variability.
AB  - Variability in the effect of subcutaneously administered insulin represents a
      major challenge in insulin therapy where precise dosing is required in order to
      achieve targeted glucose levels. Since this variability is largely influenced by
      the absorption of insulin, a deeper understanding of the factors affecting the
      absorption of insulin from the subcutaneous tissue is necessary in order to
      improve glycaemic control and the long-term prognosis in people with diabetes.
      These factors can be related to either the insulin preparation, the injection
      site/patient, or the injection technique. This review highlights the factors
      affecting insulin absorption with special attention on the physiological factors
      at the injection site. In addition, it also provides a detailed description of
      the insulin absorption process and the various modifications to this process that
      have been utilized by the different insulin preparations available.

PMID- 30116736
TI  - Adipocyte DIO2 Expression Increases in Human Obesity but Is Not Related to
      Systemic Insulin Sensitivity.
AB  - Deiodinase type II (D2), encoded by DIO2, catalyzes the conversion of T4 to
      bioactive T3. T3 not only stimulates adaptive thermogenesis but also affects
      adipose tissue (AT) lipid accumulation, mitochondrial function, inflammation, and
      potentially systemic metabolism. Although better defined in brown AT, the precise
      role of DIO2 expression in white AT remains largely unknown, with data derived
      only from whole fat. Therefore, the purpose of this study was to determine
      whether subcutaneous (SAT) and visceral (VAT) adipocyte-specific gene expression
      of DIO2 differs between obese and lean patients and whether these differences
      relate to alterations in mitochondrial function, fatty acid flux, inflammatory
      cytokines/adipokines, and ultimately insulin sensitivity. Accordingly, adipocytes
      of 73 obese and 21 lean subjects were isolated and subjected to gene expression
      analyses. Our results demonstrate that obese compared to lean human individuals
      have increased adipocyte-specific DIO2 expression in both SAT and VAT. Although
      higher DIO2 was strongly related to reduced fatty acid synthesis/oxidation and
      mitochondrial function, we found no relationship to proinflammatory cytokines or
      insulin resistance and no difference based on diabetic status. Our results
      suggest that adipocyte-derived DIO2 may play a role in weight maintenance but is
      likely not a major contributor to obesity-related insulin resistance.

PMID- 30116737
TI  - Insulin Adherence in Type 2 Diabetes in Mexico: Behaviors and Barriers.
AB  - Objective: To investigate factors associated with insulin adherence in subjects
      with type 2 diabetes mellitus (T2D) attending a tertiary care centre in Mexico
      City. Material and Methods: Cross-sectional study, including 200 patients.
      Adherence to insulin therapy was measured with a medication adherence
      questionnaire. Sociodemographic data and factors related to insulin omission were
      collected and compared between the nonadherent and adherent groups. Results: We
      categorized 117 (58.5%) patients as nonadherent and 83 (41.5%) as adherent. Among
      the adherent, only 22 patients (11%) had excellent adherence to insulin therapy.
      The following factors were associated with nonadherence: lack of planning of
      daily activities (46.1%), fear of hypoglycemia (41%), economic factors (15.4%),
      and number of insulin applications (2.31 versus 1.76 applications per day).
      Conclusions: In this study, patients with type 2 diabetes attending a tertiary
      care referral centre showed inadequate adherence to insulin therapy. The
      principal factors associated with insulin omission were low socioeconomic status,
      fear of hypoglycemia, and a greater number of insulin applications per day.

PMID- 30116738
TI  - Erratum to "Readiness of Sub-Saharan Africa Healthcare Systems for the New
      Pandemic, Diabetes: A Systematic Review".
AB  - [This corrects the article DOI: 10.1155/2018/9262395.].

PMID- 30116742
TI  - Effect of Insulin-Induced Lipodystrophy on Glycemic Control among Children and
      Adolescents with Diabetes in Tikur Anbessa Specialized Hospital, Addis Ababa,
      Ethiopia.
AB  - Background: Lipodystrophy is one of the clinical complications of insulin
      injection that affects insulin absorption and leads to poor glycemic control.
      Objective: To assess insulin-induced lipodystrophy and glycemic control. Methods:
      A cross sectional study was done on 176 diabetic children and adolescents who
      inject insulin for a minimum of one year. First, anthropometric and clinical
      characteristics of the patients were recorded in questionnaire, and then
      observation and palpation techniques were used in assessing lipodystrophy.
      Result: Out of the total 176 participants, 103 (58.5%) had insulin-induced
      lipodystrophy, of them 100 (97.1%) had lipohypertrophy and 3 (2.9%) had
      lipoatrophy. Being younger, failure to rotate the injection site every week and
      multiple reuse of insulin syringe had significant influence in development of
      insulin-induced lipohypertrophy. Lipohypertrophy in turn was associated with the
      use of higher dose of insulin and nonoptimal glycemic control. Conclusion:
      Findings of this study revealed that in spite of using recombinant human insulin,
      the magnitude of the lipohypertrophy still remained high. Therefore, a routine
      workup of insulin-injecting patients for such complication is necessary,
      especially in the individuals who have a nonoptimal glycemic control.

PMID- 30116740
TI  - DPP-4 Inhibitor Sitagliptin Improves Cardiac Function and Glucose Homeostasis and
      Ameliorates beta-Cell Dysfunction Together with Reducing S6K1 Activation and IRS
      1 and IRS-2 Degradation in Obesity Female Mice.
AB  - Background: Chronic overnutrition leads to cardiac dysfunction and insulin (INS)
      resistance. Dipeptidyl peptidase-4 (DPP-4) improves glucose metabolism and
      insulin sensitivity in both human and animal models. In this study, we explored
      whether DPP-4 inhibitor sitagliptin (SIT) is involved in the protection of
      cardiac function and beta-cell function using an obesity female mouse model.
      Methods: Six-week-old C57BL6/J mice were fed a high fat and fructose Western diet
      with DPP-4 inhibitor SIT for 12 weeks. Cardiac function was examined by
      echocardiography. Body weight, plasma glucose, and insulin concentrations were
      measured. The contents of total S6 kinase 1 (S6K1), phosphorylation of S6K1
      activation, and INS docking proteins INS receptor substrates 1 and 2 (IRS-1, IRS
      2) were assayed, and histology of heart tissue was performed. Results: Chronic
      Western diet consumption elevated plasma glucose and insulin and caused obesity,
      diastolic dysfunction, and beta-cell dysfunction. DPP-4 inhibition with SIT
      resulted in reduction in body weight, fasting glucose, and plasma insulin, and
      improved cardiac diastolic dysfunction. SIT also decreased mTOR/S6K1 activation
      and prevented the degradation of IRS-1 and IRS-2. Conclusions: This study
      revealed pleiotropic protective effects of DPP-4 inhibitor SIT on cardiac
      function, glycemia, and beta-cell function together with reducing S6K1 activation
      and IRS-1 and IRS-2 degradation in the obesity female mouse model.

PMID- 30116741
TI  - The All-Cause Mortality and a Screening Tool to Determine High-Risk Patients
      among Prevalent Type 2 Diabetes Mellitus Patients.
AB  - Aims: This study aims to determine the all-cause mortality and the associated
      risk factors for all-cause mortality among the prevalent type 2 diabetes mellitus
      (T2DM) patients within five years' period and to develop a screening tool to
      determine high-risk patients. Methods: This is a cohort study of T2DM patients in
      the national diabetes registry, Malaysia. Patients' particulars were derived from
      the database between 1st January 2009 and 31st December 2009. Their records were
      matched with the national death record at the end of year 2013 to determine the
      status after five years. The factors associated with mortality were investigated,
      and a prognostic model was developed based on logistic regression model. Results:
      There were 69,555 records analyzed. The mortality rate was 1.4 persons per 100
      person-years. The major cause of death were diseases of the circulatory system
      (28.4%), infectious and parasitic diseases (19.7%), and respiratory system
      (16.0%). The risk factors of mortality within five years were age group (p <
      0.001), body mass index category (p < 0.001), duration of diabetes (p < 0.001),
      retinopathy (p = 0.001), ischaemic heart disease (p < 0.001), cerebrovascular (p
      = 0.007), nephropathy (p = 0.001), and foot problem (p = 0.001). The sensitivity
      and specificity of the proposed model was fairly strong with 70.2% and 61.3%,
      respectively. Conclusions: The elderly and underweight T2DM patients with
      complications have higher risk for mortality within five years. The model has
      moderate accuracy; the prognostic model can be used as a screening tool to
      classify T2DM patients who are at higher risk for mortality within five years.

PMID- 30116743
TI  - Predicting Type 2 Diabetes Mellitus Occurrence Using Three-Dimensional
      Anthropometric Body Surface Scanning Measurements: A Prospective Cohort Study.
AB  - Background: An accurate and comprehensive anthropometric measure for predicting
      type 2 diabetes mellitus (T2DM) has not yet been depicted. Methods: A total of
      8450 nondiabetic participants were recruited during 2000-2010 in Taiwan. The
      cohort was followed up to the end of 2013, over an average of 8.87 years. At
      recruitment, participants completed a questionnaire related to basic
      demographics, lifestyle variables, personal disease history, and family disease
      history. 3D body surface scanning was used to obtain 35 anatomical measurements.
      A Cox proportional hazard model was used to conduct multivariable analyses.
      Results: A total of 2068 T2DM cases at an incidence rate of 27.59 * 10-3 (year-1)
      were identified during the follow-up period. Multivariable-adjusted hazard ratios
      (HRs) demonstrated that neck circumference (NC) (HR = 1.048; 95% CI = 1.033
      1.064), waist width (WW) (HR = 1.061; 95% CI = 1.040-1.081), and left thigh
      circumference (TC) (HR = 0.984; 95% CI = 0.972-0.995) were significant predictors
      of the occurrence of T2DM. While dividing body measurement into median high/low
      groups, an increased risk of T2DM was observed among participants with a larger
      NC and smaller TC (HR = 1.375; 95% CI = 1.180-1.601) and a larger WW and smaller
      TC (HR = 1.278; 95% CI = 1.085-1.505) relative to other participants.
      Conclusions: This study suggests that as well as using traditional waist and TC
      measurements, NC can be used as an indicator to provide an early prediction of
      developing T2DM, while providing clues for future mechanistic investigations of
      T2DM.

PMID- 30116739
TI  - Interactions between and Shared Molecular Mechanisms of Diabetic Peripheral
      Neuropathy and Obstructive Sleep Apnea in Type 2 Diabetes Patients.
AB  - Type 2 diabetes (T2D) accounts for about 90% of all diabetes patients and incurs
      a heavy global public health burden. Up to 50% of T2D patients will eventually
      develop neuropathy as T2D progresses. Diabetic peripheral neuropathy (DPN) is a
      common diabetic complication and one of the main causes of increased morbidity
      and mortality of T2D patients. Obstructive sleep apnea (OSA) affects over 15% of
      the general population and is associated with a higher prevalence of T2D. Growing
      evidence also indicates that OSA is highly prevalent in T2D patients probably due
      to diabetic peripheral neuropathy. However, the interrelations among diabetic
      peripheral neuropathy, OSA, and T2D hitherto have not been clearly elucidated.
      Numerous molecular mechanisms have been documented that underlie diabetic
      peripheral neuropathy and OSA, including oxidative stress, inflammation,
      endothelin-1, vascular endothelial growth factor (VEGF), accumulation of advanced
      glycation end products, protein kinase C (PKC) signaling, poly ADP ribose
      polymerase (PARP), nitrosative stress, plasminogen activator inhibitor-1, and
      vitamin D deficiency. In this review, we seek to illuminate the relationships
      among T2D, diabetic peripheral neuropathy, and OSA and how they interact with one
      another. In addition, we summarize and explain the shared molecular mechanisms
      involved in diabetic peripheral neuropathy and OSA for further mechanistic
      investigations and novel therapeutic strategies for attenuating and preventing
      the development and progression of diabetic peripheral neuropathy and OSA in T2D.

PMID- 30116744
TI  - The Effects of Tai Chi on Type 2 Diabetes Mellitus: A Meta-Analysis.
AB  - Objective: To investigate the effects of Tai chi in type 2 diabetes mellitus
      (type-2 DM) patients using systematic review and meta-analysis. Methods: Seven
      electronic resource databases were searched, and randomized controlled trials on
      the role of Tai chi in type-2 DM patients were retrieved. The meta-analysis was
      performed with RevMan 5.3, and research quality evaluation was conducted with the
      modified Jadad scale. Results: Fourteen studies, with 798 individuals related to
      the intervention of Tai chi on diabetes, were included. The results showed that,
      compared with nonexercise, Tai chi had the effect of lowering fasting blood
      glucose [MD = -1.39, 95% CI (-1.95, -0.84), P < 0.0001] and the subgroup effect
      size decreased with the increase of total exercise amount, there is no
      significant difference between Tai chi and other aerobic exercises [MD = -0.50,
      95% CI (-1.02, 0.02), P = 0.06]; compared with nonexercise, Tai chi could reduce
      HbA1c [MD = -0.21, 95% CI (-0.61, 0.19), P = 0.31], and the group effect size
      decreased with the increase of total exercise amount. The reducing HbA1c effect
      of Tai chi was better than that of other aerobic exercises, but the difference
      was at the margin of statistical significance [MD = -0.19, 95% CI (-0.37, 0.00),
      P = 0.05]; compared with nonexercise, Tai chi had the effect of reducing 2 h
      postprandial blood glucose [MD = -2.07, 95% CI (-2.89, -1.26), P = 0.0002], there
      is no significant difference between Tai chi and other aerobic exercises in
      reducing 2 h postprandial blood glucose [MD = -0.44, 95% CI (-1.42, 0.54), P =
      0.38]. Conclusion: Tai chi can effectively affect the management of blood glucose
      and HbA1c in type-2 DM patients. Long-term adherence to Tai chi has a better role
      in reducing blood glucose and HbA1c levels in type 2 DM patients.

PMID- 30116745
TI  - Neurophysiological Evidence for a Compensatory Activity during a Simple Oddball
      Task in Adolescents with Type 1 Diabetes Mellitus.
AB  - Objective: The poor metabolic control in type 1 diabetes mellitus (T1D) has a
      negative impact on the developing brain. Hyperglycemia and glycemic fluctuations
      disrupt mainly executive functions. To assess a hypothesized deficit of the
      executive functions, we evaluated visual processing and reaction time in an
      oddball task. Methods: Oddball visual event-related potentials (ERPs), reaction
      time, and pattern-reversal visual evoked potentials (VEPs) were examined in a
      cohort of twenty-two 12- to 18-year-old T1D patients without diabetic retinopathy
      at normal glycemia and in nineteen 10- to 21-year-old healthy controls. Results:
      The P100 peak time of the VEPs was significantly prolonged in T1D patients
      compared with the control group (p < 0.017). In contrast to the deteriorated
      sensory response, the area under the curve of the P3b component of the ERPs was
      significantly larger (p = 0.035) in patients, while reaction time in the same
      task did not differ between groups (p = 0.713). Conclusions: The deterioration on
      a sensory level, enhanced activity during cognitive processing, and balanced
      behavioral response support the view that neuroplasticity counterbalances the
      neural impairment by enhanced cognitive processing to achieve normal behavioral
      performance in T1D adolescents.

PMID- 30116746
TI  - Exercise Training Induced Cardioprotection with Moderate Hyperglycemia versus
      Sedentary Intensive Glycemic Control in Type 1 Diabetic Rats.
AB  - Intensive insulin therapy (IIT; 4-7 mmol/L) is the preferred treatment for type 1
      diabetes mellitus (T1DM) patients to reduce the risk of cardiovascular disease
      (CVD). However, this treatment strategy has been questioned as it is accompanied
      with a sedentary lifestyle leading to weight gain and insulin resistance. T1DM
      patients who partake in high-intensity aerobic training (AThigh) to reduce CVD
      often utilize conventional insulin therapy (CIT; 9-15 mmol/L) to offset the risk
      of hypoglycemia. Moreover, exercise modalities incorporating resistance training
      (RT) have been shown to further reduce this risk. The purpose of this
      investigation was twofold: (1) to determine if CIT paired with AThigh results in
      larger cardioprotection from an ischemia-reperfusion (I-R) injury than IIT and
      (2) to establish if the integration of RT with AThigh (ART) results in similar
      cardioprotection as AThigh. Diabetic (D) male Sprague-Dawley rats were divided
      into D-IIT (n = 12), D-CIT (n = 12), D-AThigh (n = 8), D-RT (n = 8), and D-ART (n
      = 8). T1DM was induced with streptozotocin, and blood glucose was adjusted with
      insulin. D-AThigh occurred on a treadmill (27 m/min; 1 hr), D-RT performed
      weighted ladder climbs, and D-ART alternated daily between AThigh and RT.
      Exercise occurred 5 days/wk for 12 wks. This investigation demonstrates that
      cardioprotection following an I-R injury was similar between D-AThigh and D-IIT.
      This cardioprotection is not exercise-specific, and each provides unique
      advantages. D-AThigh leads to improved glycemia while insulin sensitivity was
      enhanced following resistance exercises. Thus, exercise is an effective means to
      elicit cardioprotection in T1DM. However, in addition to glycemia, other factors
      should be considered when tailoring an exercise program for T1DM patients.

PMID- 30116747
TI  - Association between Glycemic Control and Clinic Attendance in Emerging Adults
      with Type 1 Diabetes: A Tertiary Center Experience.
AB  - Aims: The transition of emerging adults with type 1 diabetes (T1D) from pediatric
      diabetes clinics to adult clinics between 18 and 21 years of age could result in
      decreased clinic attendance and thus worsen glycemic control. Our institutional
      policy offering surveillance till age 30 enabled us to evaluate clinic attendance
      without the confounding effect of transition. Our aim was to determine the
      association between glycemic control (HbA1c) and attendance rate. Methods: The
      medical records of 261 (54% males) young adult T1D patients (median age 22.9
      years) were reviewed. Patients were stratified according to the
      attainment/nonattainment of glycemic targets (HbA1c <= 7% versus HbA1c > 7% (53
      mmol/mol)). The attendance rate was calculated as the number of clinic
      visits/number of scheduled appointments. Results: Median annual number of
      scheduled visits was 3 (3, 4); attendance rate was 75% (53.6%, 100%). Seventy
      four (28.4%) patients attained glycemic targets (median HbA1c 6.5% (48 mmol/mol)
      (6.3%, 6.8% (45.51 mmol/mol)); 187 (71.6%) patients had a median HbA1c of 7.8%
      (62 mmol/mol) (7.4%, 8.4% (57.68 mmol/mol)). The attainment of the treatment
      target was more prevalent in older patients (P = 0.006), in male patients (P =
      0.007), and in patients with higher education (P = 0.017). Higher attendance rate
      (beta (2.483), P < 0.001) and male gender (beta (0.746), P = 0.015) were
      associated with better metabolic control. Conclusions: In emerging adults with
      T1D during the ongoing stable phase of diabetes management, higher attendance
      rate, rather than absolute number of clinic visits, was associated with the
      attainment of glycemic targets.

PMID- 30116748
TI  - Host Immunological Effects of Partial Splenic Embolization in Patients with Liver
      Cirrhosis.
AB  - Purpose: Restoration of the balance between T lymphocyte subsets and between
      Th1/Th2 cytokines together with improvement of antitumor immunity has been
      reported after hepatosplenectomy in patients with liver cirrhosis (LC) and
      hepatocellular carcinoma (HCC). However, the detailed effects of partial splenic
      embolization (PSE) on host immunity are unknown. Accordingly, this study
      evaluated host immunity in patients with cirrhosis receiving PSE for
      thrombocytopenia. Methods: Twenty-three adult Japanese patients with cirrhosis
      and thrombocytopenia underwent PSE using straight coils at our hospital between
      2010 and 2015. Blood samples were collected before PSE and 4 weeks after PSE.
      Results: The platelet counts were significantly higher 4 weeks after PSE compared
      with before PSE. The white blood cell count (neutrophils, lymphocytes, and
      monocytes) also increased significantly after PSE. Furthermore, Th1 cells and Th2
      cells showed a significant increase at 4 weeks after PSE compared with before
      PSE, although there was no significant change of Treg cells. Moreover, serum
      levels of TNF-alpha, soluble TNF receptor I, and soluble Fas were significantly
      increased after PSE. There was no significant change of the Child-Pugh score.
      Conclusions: In patients with cirrhosis and thrombocytopenia, PSE not only
      promoted the recovery of leukopenia and thrombocytopenia but also induced
      activation of host immunity.

PMID- 30116749
TI  - Venom from Bothrops lanceolatus, a Snake Species Native to Martinique, Potently
      Activates the Complement System.
AB  - Bothrops lanceolatus snake venom causes systemic thrombotic syndrome but also
      local inflammation involving extensive oedema, pain, and haemorrhage. Systemic
      thrombotic syndrome may lead to fatal pulmonary embolism and myocardial and
      cerebral infarction. Here, we investigated the ability of B. lanceolatus venom to
      activate the Complement system (C) in order to improve the understanding of venom
      induced local inflammation. Data presented show that B. lanceolatus venom is able
      to activate all C-pathways. In human serum, the venom strongly induced the
      generation of anaphylatoxins, such as C5a and C4a, and the Terminal Complement
      complex. The venom also induced cleavage of purified human components C3, C4, and
      C5, with the production of biologically active C5a. Furthermore, the venom
      enzymatically inactivated the soluble C-regulator and the C1-inhibitor (C1-INH),
      and significantly increased the expression of bound C-regulators, such as MCP and
      CD59, on the endothelial cell membrane. Our observations that B. lanceolatus
      venom activates the three Complement activation pathways, resulting in
      anaphylatoxins generation, may suggest that this could play an important role in
      local inflammatory reaction and systemic thrombosis caused by the venom.
      Inactivation of C1-INH, which is also an important inhibitor of several
      coagulation proteins, may also contribute to inflammation and thrombosis. Thus,
      further in vivo studies may support the idea that therapeutic management of
      systemic B. lanceolatus envenomation could include the use of Complement
      inhibitors as adjunct therapy.

PMID- 30116752
TI  - Peptide-Based Immunotherapeutics and Vaccines 2017.

PMID- 30116750
TI  - CD4hiCD8low Double-Positive T Cells Are Associated with Graft Rejection in a
      Nonhuman Primate Model of Islet Transplantation.
AB  - Peripheral CD4/CD8 double-positive (DP) T cells are associated with autoimmune
      disorders, cancer, and viral infection. However, the relationship between organ
      transplantation and DP T cells is unclear. Here, we examined the functional
      characteristics of peripheral DP T cells and analyzed their significance with
      respect to islet graft rejection in a nonhuman primate model of islet
      transplantation. DP T cells were functionally equivalent to conventional CD4 and
      CD8 T cells in terms of helper and cytotoxic activity, respectively. DP T cells
      expressed high levels of CXCR5 and PD-1 and secreted IFN-gamma, IL-4, and IL-21
      in amounts equivalent to those secreted by CD4 or CD8 T cells; also, they
      produced large amounts of granzyme B and perforin. In addition, under steady
      state conditions, DP T cells expressed eomesodermin (Eomes) and promyelocytic
      leukemia zinc finger (PLZF) proteins, both of which act as transcription factors
      in innate/memory-like T cells. The number of peripheral DP T cells in the islet
      transplantation model was high in the group that experienced graft rejection;
      this was not the case in the long-term survival group. Interestingly, numbers of
      effector memory T cells (TEM) within the DP T cell population increased
      significantly during islet graft rejection, as did those of TEM within the
      cytotoxic CD8 T cells. Furthermore, the most conspicuous of which was the
      increase of CD4hiCD8low T cell subpopulation at that point. Taken together, the
      data suggest that peripheral DP T cells showing an innate/memory-like phenotype
      have both helper and cytotoxic activity in vitro and that they may act as a novel
      biomarker for graft rejection after islet transplantation.

PMID- 30116751
TI  - Distinct Changes of BTLA and HVEM Expressions in Circulating CD4+ and CD8+ T
      Cells in Hepatocellular Carcinoma Patients.
AB  - BTLA/HVEM (B and T lymphocyte attenuator/herpes virus entry mediator) pathways
      play a critical role in T cell suppression in tumor. However, its dynamic changes
      in different T cell subsets in peripheral blood and their clinical significance
      are largely unclear in cancer patients. In the current study, we showed distinct
      changes of BTLA and HVEM expressions on peripheral blood CD4+ and CD8+ T cells in
      patients with hepatocellular carcinoma (HCC); BTLA expression were significantly
      upregulated on circulating CD4+ but not CD8+ T cells. In sharp contrast, the
      levels of HVEM expression were significantly downregulated on circulating CD8+
      but not CD4+ T cells. A strong positive correlation between BTLA expression on
      circulating CD4+ T cells and BTLA expression on autologous CD8+ counterparts was
      observed in healthy donors but absent in HCC patients. More importantly, we found
      that blockade of the BTLA/HVEM pathway increased IFN-gamma production in both
      circulating CD4+ and CD8+ T cells. Collectively, our data suggested that the
      BTLA/HVEM pathway contributes to peripheral T cell suppression in HCC patients,
      and BTLA/HVEM may serve as attractive targets for HCC immunotherapy.

PMID- 30116754
TI  - PPAR-gamma Agonist Alleviates Liver and Spleen Pathology via Inducing Treg Cells
      during Schistosoma japonicum Infection.
AB  - Background: Peroxisome proliferator-activated receptor- (PPAR-) gamma plays
      critical roles in human metabolic disorders and has recently been implicated as a
      regulator of cellular proliferation and inflammatory responses. Regulatory T
      cells (Tregs), which express high levels of PPAR-gamma protein, have the ability
      to maintain immune tolerance to self-antigens and regulate immune response to
      Schistosoma infection. However, mechanisms involved in the resolution of these
      responses are elusive. Methods: Liver and spleen tissue samples in Schistosoma
      japonicum-infected mice after administration of pioglitazone (a PPAR-gamma
      agonist) were collected. The hepatic and splenic pathologies were detected by H&E
      and Masson staining. The percentages of Th1/2 and Treg cells in the liver and
      spleen of each mouse were determined using flow cytometry. Levels of gene
      expression of PPAR-gamma and Foxp3 in tissues or cells were determined using real
      time PCR (RT-PCR). Macrophages were treated with pioglitazone in vitro or
      cocultured with normal purified CD4+ T cells for detecting Treg cells by flow
      cytometry. The interactions of PPAR-gamma with Foxp3 in CD4+ T cells were
      detected by coimmunoprecipitation. Results: Administration of pioglitazone
      resulted in the prevention of the development of hepatic and splenic pathologies.
      Activation of PPAR-gamma by pioglitazone resulted in increased percentages of
      CD4+CD25+Foxp3+ Treg cells and decreased percentages of CD3+CD4+IFN-gamma+ and
      CD3+CD4+IL-4+ cells in the liver and spleen of Schistosoma japonicum-infected
      mice. In addition, the PPAR-gamma agonist can induce Treg cells in vitro directly
      or by modulating the macrophage's function indirectly. Furthermore, through
      interaction with Foxp3 in CD4+ T cells, the PPAR-gamma agonist can promote the
      expression of Foxp3; however, the inhibitor of PPAR-gamma weakened the expression
      of Foxp3 by modifying the coexpression of Foxp3 and PPAR-gamma. Conclusions: Our
      study reveals a previously unrecognized role for PPAR-gamma/Foxp3 signaling in
      regulating the immunopathology that occurs during Schistosoma infection through
      induction of Treg cells.

PMID- 30116753
TI  - Protective Role of gammadelta T Cells in Different Pathogen Infections and Its
      Potential Clinical Application.
AB  - gammadelta T cells, a subgroup of T cells based on the gammadelta TCR, when
      compared with conventional T cells (alphabeta T cells), make up a very small
      proportion of T cells. However, its various subgroups are widely distributed in
      different parts of the human body and are attractive effectors for infectious
      disease immunity. gammadelta T cells are activated and expanded by nonpeptidic
      antigens (P-Ags), major histocompatibility complex (MHC) molecules, and lipids
      which are associated with different kinds of pathogen infections. Activation and
      proliferation of gammadelta T cells play a significant role in diverse infectious
      diseases induced by viruses, bacteria, and parasites and exert their potential
      effector function to effectively eliminate infection. It is well known that many
      types of infectious diseases are detrimental to human life and health and give
      rise to high incidence of illnesses and death rate all over the world. To date,
      there is no comprehensive understanding of the correlation between gammadelta T
      cells and infectious diseases. In this review, we will focus on the various
      subgroups of gammadelta T cells (mainly Vdelta1 T cells and Vdelta2 T cells)
      which can induce multiple immune responses or effective functions to fight
      against common pathogen infections, such as Mycobacterium tuberculosis, Listeria
      monocytogenes, influenza viruses, HIV, EBV, and HBV. Hopefully, the gamma-delta T
      cell study will provide a novel effective way to treat infectious diseases.

PMID- 30116757
TI  - Naturally Derived Anti-HIV Polysaccharide Peptide (PSP) Triggers a Toll-Like
      Receptor 4-Dependent Antiviral Immune Response.
AB  - Aim: Intense interest remains in the identification of compounds to reduce human
      immunodeficiency virus type 1 (HIV-1) replication. Coriolus versicolor's
      polysaccharide peptide (PSP) has been demonstrated to possess immunomodulatory
      properties with the ability to activate an innate immune response through Toll
      like receptor 4 (TLR4) showing insignificant toxicity. This study sought to
      determine the potential use of PSP as an anti-HIV agent and whether its antiviral
      immune response was TLR4 dependent. Materials and Methods: HIV-1 p24 and anti-HIV
      chemokine release was assessed in HIV-positive (HIV+) THP1 cells and validated in
      HIV+ peripheral blood mononuclear cells (PBMCs), to determine PSP antiviral
      activity. The involvement of TLR4 activation in PSP anti-HIV activity was
      evaluated by inhibition. Results: PSP showed a promising potential as an anti-HIV
      agent, by downregulating viral replication and promoting the upregulation of
      specific antiviral chemokines (RANTES, MIP-1alpha/beta, and SDF-1alpha) known to
      block HIV-1 coreceptors in THP1 cells and human PBMCs. PSP produced a 61% viral
      inhibition after PSP treatment in HIV-1-infected THP1 cells. Additionally, PSP
      upregulated the expression of TLR4 and TLR4 inhibition led to countereffects in
      chemokine expression and HIV-1 replication. Conclusion: Taken together, these
      findings put forward the first evidence that PSP exerts an anti-HIV activity
      mediated by TLR4 and key antiviral chemokines. Elucidating these new molecular
      mediators may reveal additional drug targets and open novel therapeutic avenues
      for HIV-1 infection.

PMID- 30116756
TI  - DNA Damage and Deficiencies in the Mechanisms of Its Repair: Implications in the
      Pathogenesis of Systemic Lupus Erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a perplexing and potentially severe
      disease, the pathogenesis of which is yet to be understood. SLE is considered to
      be a multifactorial disease, in which genetic factors, immune dysregulation, and
      environmental factors, such as ultraviolet radiation, are involved. Recently, the
      description of novel genes conferring susceptibility to develop SLE even in their
      own (monogenic lupus) has raised the interest in DNA dynamics since many of these
      genes are linked to DNA repair. Damage to DNA induces an inflammatory response
      and eventually triggers an immune response, including those targeting self
      antigens. We review the evidence that indicates that patients with SLE present
      higher levels of DNA damage than normal subjects do and that several proteins
      involved in the preservation of the genomic stability show polymorphisms, some of
      which increase the risk for SLE development. Also, the experience from animal
      models reinforces the connection between DNA damage and defective repair in the
      development of SLE-like disease including characteristic features such as anti
      DNA antibodies and nephritis. Defining the role of DNA damage response in SLE
      pathogenesis might be strategic in the quest for novel therapies.

PMID- 30116759
TI  - Construction and Characterization of Adenovirus Vectors Encoding Aspartate-beta
      Hydroxylase to Preliminary Application in Immunotherapy of Hepatocellular
      Carcinoma.
AB  - Dendritic cells (DCs) harboring tumor-associated antigen are supposed to be a
      potential immunotherapy for hepatocellular carcinoma (HCC). Aspartate-beta
      hydroxylase (AAH), an overexpressed tumor-associated cell surface protein, is
      considered as a promising biomarker and therapeutic target for HCC. In this
      study, we constructed adenovirus vector encoding AAH gene by gateway recombinant
      cloning technology and preliminarily explored the antitumor effects of DC
      vaccines harboring AAH. Firstly, the total AAH mRNA was extracted from human HCC
      tissues; the cDNA was amplified by RT-PCR, verified, and sequenced after TA
      cloning. Gateway technology was used and the obtained 18T-AAH was used as a
      substrate, to yield the final expression vector Ad-AAH-IRES2-EGFP. Secondly, bone
      marrow-derived DCs were infected by Ad-AAH-IRES2-EGFP to yield AAH-DC vaccines.
      Matured DCs were demonstrated by increased expression of CD11c, CD80, and MHC-II
      costimulatory molecules. A dramatically cell-killing effect of T lymphocytes
      coculturing with AAH-DCs on HepG2 HCC cell line was demonstrated by CCK-8 and FCM
      assays in vitro. More importantly, in an animal experiment, the lysis effect of
      cytotoxic T lymphocytes (CTLs) on HepG2 cells in the AAH-DC group was stronger
      than that in the control groups. In conclusion, the gateway recombinant cloning
      technology is a powerful method of constructing adenovirus vector, and the
      product Ad-AAH-IRES2-EGFP may present as a potential candidate for DC-based
      immunotherapy of HCC.

PMID- 30116758
TI  - Analysis of Sodium Chloride Intake and Treg/Th17 Lymphocytes in Healthy
      Individuals and Patients with Rheumatoid Arthritis or Systemic Lupus
      Erythematosus.
AB  - We assessed different immune parameters in patients with rheumatoid arthritis
      (RA) and systemic lupus erythematosus (SLE) with low (LSI) and high (HSI) sodium
      intake. Thirty-eight patients with RA, thirty-seven with SLE, and twenty-eight
      healthy subjects were studied and classified as LSI or HSI. Levels and
      suppressive function of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were
      determined by flow cytometry in blood samples. Levels and in vitro
      differentiation of Th17 cells were also assessed. Similar levels of
      CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg cells were observed in LSI and HSI
      patients or controls. However, a positive correlation was detected between sodium
      intake and levels of CD4+CD25+Foxp3+ Treg cells in SLE and a negative association
      between CD4+CD69+Foxp3- Treg cells and sodium intake in RA. No other significant
      associations were detected, including disease activity and sodium intake.
      Moreover, the suppressor activity of CD4+CD25+Foxp3+ and CD4+CD69+Foxp3- Treg
      cells was similar in LSI and HSI patients or controls. The levels and in vitro
      differentiation of Th17 cells were also similar in LSI and HSI individuals. Our
      results suggest that, in the population studied (Mexican mestizo), the level of
      sodium intake is not apparently associated with different relevant immune
      parameters in healthy subjects or patients with SLE or RA.

PMID- 30116761
TI  - Return to Level I Sports After Anterior Cruciate Ligament Reconstruction:
      Evaluation of Age, Sex, and Readiness to Return Criteria.
AB  - Background: Return to sport (RTS) after anterior cruciate ligament (ACL)
      reconstruction is a topic of current interest. The high reinjury rates reported
      in younger athletes may be due in part to an early RTS. Purpose: To determine the
      proportion of athletes who return to level I (jumping, hard pivoting, and
      cutting) sport at less than 1 year after ACL reconstruction and compare return
      rates by age and sex. A secondary purpose was to examine whether RTS is
      associated with some commonly used outcome criteria. Methods: A cohort of 1440
      athletes (992 males, 448 females) satisfied criteria for inclusion in this study
      (primary ACL reconstruction, normal contralateral knee, no additional surgery
      within the first year after the reconstruction, and participation in level I
      sport on a weekly basis prior to injury). The proportion of athletes in this
      sample who had resumed level I sport by 12 months after surgery was recorded,
      along with measurements of knee function (single-legged hop symmetry), laxity (KT
      1000 arthrometer), and self-reported outcomes (International Knee Documentation
      Committee [IKDC] subjective score). Limb symmetry index scores of 90 or higher,
      side-to-side difference in anterior knee laxity of 2 mm or less, and IKDC scores
      of 95 or higher were considered indicators of satisfactory recovery from surgery.
      Results: Rates of return to level I sport were significantly higher for athletes
      aged 25 years and younger (48% return rate) compared with older athletes (26-35
      years, 32% return rate [P < .0001]; >=36 years, 19% return rate [P < .001]). Male
      athletes who were in the <=25-year and 26- to 35-year age brackets had
      significantly higher return rates than female athletes (52% vs 39% and 37% vs
      18%, respectively), whereas no sex-based differences in RTS were seen after 36
      years of age. A significantly higher proportion of younger patients met the
      selected indicators of a satisfactory recovery. Regardless of age, athletes had
      twice the odds of RTS if they had limb symmetry index scores of 90 or higher (P
      <= .0001) and 3 times the odds of RTS if they had IKDC scores of 95 or higher (P
      < .0001). Conclusion: Almost half of younger athletes (aged <=25 years) in the
      current cohort returned to level I sports within 12 months after ACL
      reconstruction. Younger athletes were also more likely to meet criteria that
      indicate a satisfactory functional recovery and that have been used to indicate
      readiness to RTS. There may be a role for adjusting thresholds for these criteria
      based on age.

PMID- 30116760
TI  - Primary Endoscopic Closure of Duodenal Perforation Secondary to Biliary Stent
      Migration: A Case Report and Review of the Literature.
AB  - Duodenal perforation due to biliary stent migration is rare, and it often
      requires surgical repair; however, endoscopic closure has recently become a
      viable option in the appropriate patients. We present the case of a 79-year-old
      female who underwent biliary stent placement for a common bile duct stricture,
      who subsequently was found to have a duodenal wall perforation secondary to stent
      migration. The stent was extracted endoscopically with successful defect closure
      using a ConMed(r) repositional DuraClipTM. We aim to contribute to the limited
      body of literature that describes endoscopic repair of duodenal perforation
      secondary to biliary stent migration using through-the-scope endoclips.

PMID- 30116762
TI  - Using Stress Ultrasonography to Understand the Risk of UCL Injury Among
      Professional Baseball Pitchers Based on Ligament Morphology and Dynamic
      Abnormalities.
AB  - Background: Ulnar collateral ligament (UCL) injury of the elbow is a common and
      debilitating problem seen frequently among elite baseball pitchers. Ultrasound is
      a useful diagnostic tool in evaluating UCL injuries. Hypothesis: Evaluation with
      stress ultrasound of the elbow to measure the morphology of the UCL and the
      ulnohumeral joint space gapping is indicative of higher risk of UCL injury among
      professional baseball pitchers. Study Design: Cohort study; Level of evidence, 2.
      Methods: Ultrasound imaging was used to assess the medial joint laxity of the
      elbow of 70 asymptomatic professional baseball pitchers during spring training.
      Medial joint laxity and UCL morphology were assessed with OsiriX imaging software
      under 2 conditions-gravity valgus load and 5.5 lb of valgus load per a handheld
      dynamometer-with the shoulder in the maximal cocking position and the elbow in 90
      degrees  of flexion. Two trials of resting position, elbow gapping, and UCL
      thickness were collected, measured, and averaged for data analysis. Intra- and
      interrater reliabilities were established and maintained, with intraclass
      correlation coefficients in the acceptable range for all measures (0.84-0.99).
      One-way analysis of variance was used to compare dominant variables between those
      pitchers who sustained a subsequent UCL injury and those who did not. A receiver
      operating curve was used to identify pitchers who, based on elbow gapping
      measures (by cut score), were at high risk versus low risk for UCL injury.
      Results: Players who went on to injure the UCL (n = 7) displayed a significantly
      wider opening under 5.5 lb of applied stress (6.5 +/- 1.2 vs 5.3 +/- 1.2 mm, P =
      .01) when compared with pitchers without UCL injury history (n = 63); they also
      presented a trend toward wider dominant arm resting joint opening (4.9 +/- 1.2 vs
      4.0 +/- 1.1 mm, P = .07). Professional pitchers with valgus stress ulnohumeral
      joint gapping >=5.6 mm (area underneath the curve, 0.77; P = .02) of the dominant
      arm were at a 6-times greater risk of sustaining a UCL tear requiring
      reconstruction within a season. Conclusion: Our data suggest that ultrasound
      evaluation of UCL morphology may be indicative of pitchers who are at risk of
      sustaining UCL injury and that it may improve player assessment.

PMID- 30116755
TI  - Neuroblastoma Origin and Therapeutic Targets for Immunotherapy.
AB  - Neuroblastoma is a pediatric solid cancer of heterogeneous clinical behavior. The
      unique features of this type of cancer frequently hamper the process of
      determining clinical presentation and predicting therapy effectiveness. The tumor
      can spontaneously regress without treatment or actively develop and give rise to
      metastases despite aggressive multimodal therapy. In recent years, immunotherapy
      has become one of the most promising approaches to the treatment of
      neuroblastoma. Still, only one drug for targeted immunotherapy of neuroblastoma,
      chimeric monoclonal GD2-specific antibodies, is used in the clinic today, and its
      application has significant limitations. In this regard, the development of
      effective and safe GD2-targeted immunotherapies and analysis of other potential
      molecular targets for the treatment of neuroblastoma represents an important and
      topical task. The review summarizes biological characteristics of the origin and
      development of neuroblastoma and outlines molecular markers of neuroblastoma and
      modern immunotherapy approaches directed towards these markers.

PMID- 30116764
TI  - Safety Profile and Short-term Outcomes of BST-CarGel as an Adjunct to
      Microfracture for the Treatment of Chondral Lesions of the Hip.
AB  - Background: Acetabular cartilage lesions are a common abnormality found in
      patients undergoing hip arthroscopic surgery and may cause pain and functional
      limitations. Several strategies have been developed to treat chondral defects,
      with no overwhelming success. Recently, BST-CarGel has gained interest as a
      scaffolding material that can be injected into the microfracture site to
      stabilize the clot and facilitate cartilage repair. Purpose: To perform a
      retrospective analysis of prospectively collected data to evaluate the safety
      profile and short-term clinical and radiographic outcomes of patients treated
      arthroscopically with BST-CarGel for acetabular chondral defects in conjunction
      with microfracture. Study Design: Case series; Level of evidence, 4. Methods: A
      retrospective chart review was performed on all patients who underwent hip
      arthroscopic surgery by the senior surgeon to identify those who had BST-CarGel
      applied to their hip from November 2014 to July 2016, and basic demographic
      information for those patients was obtained. Operative reports and patient charts
      were reviewed to assess intraoperative and postoperative complications as well as
      to obtain the details of surgery, including lesion size and treatment method of
      the labrum (repair vs reconstruction). All patients filled out self-reported
      questionnaires, including the international Hip Outcome Tool (iHOT), Hip Outcome
      Score-Activities of Daily Living (HOS-ADL), and Hip Outcome Score-Sports Profile
      (HOS-SP) at the time of consultation and at 1 year postoperatively, and results
      were used to assess the clinical outcomes of surgery. Results: Thirty-seven
      patients (37 hips) with a mean age of 36.19 years at the time of the index
      procedure were evaluated. There were 30 male patients, and 20 procedures were
      performed on the right hip. The minimum follow-up was 1 year, with a mean follow
      up of 12.72 months. There were no major adverse events of deep vein thrombosis,
      blood vessel or nerve damage, hemarthrosis, arthralgia, or device-related adverse
      events. Two patients (5.4%) were readmitted because of pain, probably resulting
      from an inflammatory reaction to BST-CarGel. At 1 year postoperatively, there
      were statistically significant improvements in the iHOT (40.4 to 59.1; P < .001),
      HOS-ADL (60.6 to 71.4; P = .02), and HOS-SP (36.9 to 51.6; P = .01) scores. When
      the patients were subdivided based on the chondral defect size, the iHOT score
      improved for all chondral defect sizes, and the HOS-SP score improved in patients
      with medium (2-4 cm2) and very large (>6 cm2) chondral defects. In addition, the
      iHOT score improved whether the patients had their labrum repaired or
      reconstructed (P < .001 and P = .02, respectively). Conclusion: The arthroscopic
      treatment of chondral acetabular defects with BST-CarGel demonstrates a
      satisfactory safety profile, with statistically significant improvement in
      patient-reported clinical outcome scores, even for those with very large chondral
      defect sizes.

PMID- 30116763
TI  - Influence of the Anterolateral Ligament on Knee Laxity: A Biomechanical Cadaveric
      Study Measuring Knee Kinematics in 6 Degrees of Freedom Using Dynamic
      Radiostereometric Analysis.
AB  - Background: An anterior cruciate ligament (ACL) rupture often occurs during
      rotational trauma to the knee and may be associated with damage to extracapsular
      knee rotation-stabilizing structures such as the anterolateral ligament (ALL).
      Purpose: To investigate ex vivo knee laxity in 6 degrees of freedom with and
      without ALL reconstruction as a supplement to ACL reconstruction. Study Design:
      Controlled laboratory study. Methods: Cadaveric knees (N = 8) were analyzed using
      dynamic radiostereometry during a controlled pivotlike dynamic movement simulated
      by motorized knee flexion (0 degrees  to 60 degrees ) with 4-N.m internal
      rotation torque. We tested the cadaveric specimens in 5 successive ligament
      situations: intact, ACL lesion, ACL + ALL lesion, ACL reconstruction, and ACL +
      ALL reconstruction. Anatomic single-bundle reconstruction methods were used for
      both the ACL and the ALL, with a bone-tendon quadriceps autograft and gracilis
      tendon autograft, respectively. Three-dimensional kinematics and articular
      surface interactions were used to determine knee laxity. Results: For the entire
      knee flexion motion, an ACL + ALL lesion increased the mean knee laxity (P <
      .005) for internal rotation (2.54 degrees ), anterior translation (1.68 mm), and
      varus rotation (0.53 degrees ). Augmented ALL reconstruction reduced knee laxity
      for anterior translation (P = .003) and varus rotation (P = .047) compared with
      ACL + ALL-deficient knees. Knees with ACL + ALL lesions had more internal
      rotation (P < .001) and anterior translation (P < .045) at knee flexion angles
      below 40 degrees  and 30 degrees , respectively, compared with healthy knees.
      Combined ACL + ALL reconstruction did not completely restore native
      kinematics/laxity at flexion angles below 10 degrees  for anterior translation
      and below 20 degrees  for internal rotation (P < .035). ACL + ALL reconstruction
      was not found to overconstrain the knee joint. Conclusion: Augmented ALL
      reconstruction with ACL reconstruction in a cadaveric setting reduces internal
      rotation, varus rotation, and anterior translation knee laxity similar to knee
      kinematics with intact ligaments, except at knee flexion angles between 0 degrees
      and 20 degrees . Clinical Relevance: Patients with ACL injuries can potentially
      achieve better results with augmented ALL reconstruction along with ACL
      reconstruction than with stand-alone ACL reconstruction. Furthermore, dynamic
      radiostereometry provides the opportunity to examine clinical patients and
      compare the recontructed knee with the contralateral knee in 6 degrees of
      freedom.

PMID- 30116765
TI  - A Relational Perspective on Social Support Between Bereaved and Their Networks
      After Terror: A Qualitative Study.
AB  - The aim of this study is to increase the understanding of social network support
      after traumatic deaths and, by demonstrating the complexities of such encounters,
      to highlight whether such support may be totally beneficial. A phenomenological
      dynamic and relational perspective was applied to 22 in-depth interviews with
      parents bereaved as a result of the 2011 terror attack in Norway. Three main
      themes were identified in respect of interactional support processes: (a) valued
      support, (b) stressful experiences, and (c) interactive barriers. As well as
      describing the value of experienced support, the article also elaborates on the
      effect of lacking, avoidant, and inept support. The findings show that insecure
      communication and a nonmatching understanding of time and emotional overload can
      form interactive barriers between the bereaved and their networks. By better
      understanding the relational regulation processes inherent in social support we
      may provide informed advice to both the bereaved and their networks to maximize
      recovery.

PMID- 30116766
TI  - Pursuing the Mission: How Homeless Veterans Manage Chronic Disease.
AB  - The purpose of this study was to describe and explain the process by which
      homeless veterans manage their chronic health problems. In the United States,
      over 550,000 people experience homelessness on any given night. Of these, over
      11% are veterans of the military, many whom suffer from at least one chronic
      disease. Study participants included male homeless veterans with at least one
      chronic health problem recruited at a Veterans Affairs emergency department, a
      homeless shelter, and a soup kitchen. Semi-structured interviews with 32 veterans
      from the Vietnam/post-Vietnam era were audio-recorded, verified, and coded
      resulting in a theory entitled "pursuing the mission," which describes and
      explains four ways (deferring, exploring, embarking, embracing) they manage their
      chronic health problems. The findings from this study provide insight from
      individuals living this experience and will help guide the future delivery of
      health care to homeless veterans.

PMID- 30116768
TI  - Recent Advances in Laboratory Assessment of Emotion Regulation.
AB  - Over the past 15 years, the emotion regulation perspective has been widely
      integrated into theoretical and applied contexts in clinical psychology and
      beyond. Recent refinements to behavioral, subjective, psychophysiological and
      neuroimaging methods allow emotion regulation to be captured and assessed in the
      laboratory with greater precision. Technological advances enabling investigators
      to leverage information from multiple modalities are increasingly accessible, and
      as such, will further efforts to generate testable hypotheses about specific
      mechanisms implicated in emotion regulation and difficulties therein. In
      combination with theory-driven design, progressively sophisticated methods for
      laboratory assessment have potential to further emotion regulation as both a
      valid scientific construct and a useful paradigm for human emotion and behavior
      that has applicability to both clinical and non-clinical contexts.

PMID- 30116767
TI  - Associations between trabecular bone score and biochemistry in surgically vs
      conservatively treated outpatients with primary hyperparathyroidism: A
      retrospective cohort study.
AB  - Purpose: Trabecular Bone Score (TBS) is a software-based method for indirect
      assessment of trabecular bone structure of the spine, based on analysis of pixels
      in dual energy x-ray absorptiometry (DXA) images. Few studies describe the use of
      TBS in patients with primary hyperparathyroidism (PHPT). This study aimed at
      further describing this relationship, investigating possible correlations between
      biochemistry, body mass index (BMI), fracture incidence and TBS. Methods: Cross
      sectional study of 195 patients with verified PHPT, surgically (27) or
      conservatively (168) treated at the Department of Endocrinology, Aalborg
      University Hospital. TBS was acquired by reanalyzing DXA-images of the included
      subjects from the outpatient clinic. Biochemical variables were obtained from
      clinical routine blood samples taken in relation to the DXA-scans. History of
      fractures and medical history was obtained from radiology reports and medical
      charts. Results: Patients with active PHPT had a TBS-score signifying a partly
      degraded bone structure, whereas surgically treated patients had a normal bone
      structure as judged by TBS, though the difference in TBS-score was not
      statistically significant. Use of antiresorptive treatment was negatively
      associated with BMD but not TBS. No correlations between the biochemical
      variables and TBS were found. A negative correlation between TBS and BMI in
      patients with PHPT was present. Patients experiencing a fragility fracture had a
      significantly lowered TBS, BMD and T-Score. Conclusion: Biochemistry does not
      seem to predict bone status in terms of TBS in patients with PHPT. TBS is
      negatively correlated to BMI, which is also seen in patients not suffering from
      PHPT. The lack of a predictive value for antiresorptive treatment for TBS may
      raise concern. TBS appears to have a predictive value when assessing risk of
      fracture in patients with PHPT. Mini abstract: This cross-sectional study
      investigates possible correlations between biochemical variables, body mass index
      (BMI) and trabecular bone score (TBS) in 195 patients with primary
      hyperparathyroidism. It finds no correlation between biochemical variables and
      TBS, but finds a negative correlation between TBS and BMI and a clear association
      between fracture incidence and low TBS-score.

PMID- 30116769
TI  - REM sleep and safety signal learning in posttraumatic stress disorder: A
      preliminary study in military veterans.
AB  - Background: Posttraumatic Stress Disorder (PTSD) is associated with a number of
      negative physical and mental health consequences. Fear conditioning plays an
      important mechanistic role in PTSD, and PTSD patients also show deficits in
      safety signal learning. Sleep, particularly REM sleep, is linked to improved
      safety learning and extinction processes in animal models and healthy humans. No
      studies have examined the link between REM sleep and safety signal learning or
      extinction memory in clinical populations. Methods: This study examined the
      relationship between REM sleep, safety signal learning, and extinction processes
      in veterans with PTSD (n = 13). Patients' overnight sleep was characterized in
      the laboratory via polysomnography (PSG). The next day, participants underwent a
      fear conditioning paradigm during which they acquired fear toward a visual cue.
      This testing session also included a visual cue that became a safety signal (CS
      ). Following conditioning, the veterans' sleep was monitored overnight again,
      after which they underwent extinction training. Following a third night of sleep,
      extinction recall and safety recall were tested. Bivariate correlations examined
      the relationship between the slope of safety signal learning and subsequent REM
      sleep, as well as the relationship between REM sleep and subsequent extinction
      recall and safety recall on the last day of testing. Results: Veterans learned to
      differentiate the CS+ and the CS- on the first day of testing. Veterans who
      underwent safety learning more quickly on the first day of testing showed more
      efficient REM sleep that night (r = .607, p = .028). On the second day of
      testing, the patients successfully underwent extinction learning. Patients with a
      higher percentage of REM sleep on the last night of the study showed more safety
      recall early on the last day of testing (r = .688, p = .009). Conclusion: To our
      knowledge, this was the first study to examine the relationship between objective
      sleep and fear-potentiated startle performance in veterans with PTSD. Study
      methods were well tolerated by participants, supporting feasibility of the
      experimental design. Results indicated REM sleep was associated with both initial
      safety learning and subsequent safety recall. Taken together with previous
      studies in healthy controls, these preliminary results provide additional
      evidence suggesting REM sleep could play a mechanistic role in the maintenance of
      PTSD and thus identify a modifiable biological process to target in treatment of
      PTSD. These findings should be replicated in larger samples.

PMID- 30116772
TI  - Data-Driven Tree Transforms and Metrics.
AB  - We consider the analysis of high dimensional data given in the form of a matrix
      with columns consisting of observations and rows consisting of features. Often
      the data is such that the observations do not reside on a regular grid, and the
      given order of the features is arbitrary and does not convey a notion of
      locality. Therefore, traditional transforms and metrics cannot be used for data
      organization and analysis. In this paper, our goal is to organize the data by
      defining an appropriate representation and metric such that they respect the
      smoothness and structure underlying the data. We also aim to generalize the joint
      clustering of observations and features in the case the data does not fall into
      clear disjoint groups. For this purpose, we propose multiscale data-driven
      transforms and metrics based on trees. Their construction is implemented in an
      iterative refinement procedure that exploits the co-dependencies between features
      and observations. Beyond the organization of a single dataset, our approach
      enables us to transfer the organization learned from one dataset to another and
      to integrate several datasets together. We present an application to breast
      cancer gene expression analysis: learning metrics on the genes to cluster the
      tumor samples into cancer sub-types and validating the joint organization of both
      the genes and the samples. We demonstrate that using our approach to combine
      information from multiple gene expression cohorts, acquired by different
      profiling technologies, improves the clustering of tumor samples.

PMID- 30116773
TI  - Educational Case: A Uterine Neoplasm: Leiomyoma-A Benign Neoplasm.
AB  - The following fictional case is intended as a learning tool within the Pathology
      Competencies for Medical Education (PCME), a set of national standards for
      teaching pathology. These are divided into three basic competencies: Disease
      Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and
      Therapeutic Pathology. For additional information, and a full list of learning
      objectives for all three competencies, see
      http://journals.sagepub.com/doi/10.1177/2374289517715040.

PMID- 30116771
TI  - Communication Between Enteric Neurons, Glia, and Nociceptors Underlies the
      Effects of Tachykinins on Neuroinflammation.
AB  - Background & Aims: Tachykinins are involved in physiological and
      pathophysiological mechanisms in the gastrointestinal tract. The major sources of
      tachykinins in the gut are intrinsic enteric neurons in the enteric nervous
      system and extrinsic nerve fibers from the dorsal root and vagal ganglia.
      Although tachykinins are important mediators in the enteric nervous system, how
      they contribute to neuroinflammation through effects on neurons and glia is not
      fully understood. Here, we tested the hypothesis that tachykinins contribute to
      enteric neuroinflammation through mechanisms that involve intercellular neuron
      glia signaling. Methods: We used immunohistochemistry and quantitative real-time
      polymerase chain reaction, and studied cellular activity using transient-receptor
      potential vanilloid-1 (TRPV1)tm1(cre)Bbm/J::Polr2atm1(CAG-GCaMP5g,-tdTomato)Tvrd
      and Sox10CreERT2::Polr2atm1(CAG-GCaMP5g,-tdTomato)Tvrd mice or Fluo-4. We used
      the 2,4-di-nitrobenzene sulfonic acid (DNBS) model of colitis to study
      neuroinflammation, glial reactivity, and neurogenic contractility. We used
      Sox10::CreERT2+/-/Rpl22tm1.1Psam/J mice to selectively study glial
      transcriptional changes. Results: Tachykinins are expressed predominantly by
      intrinsic neuronal varicosities whereas neurokinin-2 receptors (NK2Rs) are
      expressed predominantly by enteric neurons and TRPV1-positive neuronal
      varicosities. Stimulation of NK2Rs drives responses in neuronal varicosities that
      are propagated to enteric glia and neurons. Antagonizing NK2R signaling enhanced
      recovery from colitis and prevented the development of reactive gliosis,
      neuroinflammation, and enhanced neuronal contractions. Inflammation drove changes
      in enteric glial gene expression and function, and antagonizing NK2R signaling
      mitigated these changes. Neurokinin A-induced neurodegeneration requires glial
      connexin-43 hemichannel activity. Conclusions: Our results show that tachykinins
      drive enteric neuroinflammation through a multicellular cascade involving enteric
      neurons, TRPV1-positive neuronal varicosities, and enteric glia. Therapies
      targeting components of this pathway could broadly benefit the treatment of
      dysmotility and pain after acute inflammation in the intestine.

PMID- 30116770
TI  - Identification of Positively and Negatively Selected Driver Gene Mutations
      Associated With Colorectal Cancer With Microsatellite Instability.
AB  - Background & Aims: Recent studies have shown that cancers arise as a result of
      the positive selection of driver somatic events in tumor DNA, with negative
      selection playing only a minor role, if any. However, these investigations were
      concerned with alterations at nonrepetitive sequences and did not take into
      account mutations in repetitive sequences that have very high pathophysiological
      relevance in the tumors showing microsatellite instability (MSI) resulting from
      mismatch repair deficiency investigated in the present study. Methods: We
      performed whole-exome sequencing of 47 MSI colorectal cancers (CRCs) and
      confirmed results in an independent cohort of 53 MSI CRCs. We used a
      probabilistic model of mutational events within microsatellites, while adapting
      pre-existing models to analyze nonrepetitive DNA sequences. Negatively selected
      coding alterations in MSI CRCs were investigated for their functional and
      clinical impact in CRC cell lines and in a third cohort of 164 MSI CRC patients.
      Results: Both positive and negative selection of somatic mutations in DNA repeats
      was observed, leading us to identify the expected true driver genes associated
      with the MSI-driven tumorigenic process. Several coding negatively selected MSI
      related mutational events (n = 5) were shown to have deleterious effects on tumor
      cells. In the tumors in which deleterious MSI mutations were observed despite the
      negative selection, they were associated with worse survival in MSI CRC patients
      (hazard ratio, 3; 95% CI, 1.1-7.9; P = .03), suggesting their anticancer impact
      should be offset by other as yet unknown oncogenic processes that contribute to a
      poor prognosis. Conclusions: The present results identify the positive and
      negative driver somatic mutations acting in MSI-driven tumorigenesis, suggesting
      that genomic instability in MSI CRC plays a dual role in achieving tumor cell
      transformation. Exome sequencing data have been deposited in the European genome
      phenome archive (accession: EGAS00001002477).

PMID- 30116774
TI  - Educational Case: Death Certification and the Role of the Medical
      Examiner/Coroner.
AB  - The following fictional case is intended as a learning tool within the Pathology
      Competencies for Medical Education (PCME), a set of national standards for
      teaching pathology. These are divided into three basic competencies: Disease
      Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and
      Therapeutic Pathology. For additional information, and a full list of learning
      objectives for all three competencies, see
      http://journals.sagepub.com/doi/10.1177/2374289517715040.

PMID- 30116775
TI  - Molecular signatures and functional analysis of beige adipocytes induced from in
      vivo intra-abdominal adipocytes.
AB  - Beige adipocytes can be induced from white adipocytes and precursors upon
      stimulation by cold temperatures and act like brown adipocytes to increase energy
      expenditure. Most in vivo studies examining the mechanisms for the induction of
      beige adipocytes have focused on subcutaneous white adipose tissue (sWAT; benign
      fat) in the mouse. How intra-abdominal WAT (aWAT; malignant fat) develops into
      beige adipocytes remains obscure, largely because there is a lack of a good
      animal model for the induction of beige adipocytes from aWAT. To better
      understand the development of beige adipocytes from mammalian WATs, especially
      aWAT, we induced beige adipocytes from bat aWAT and mouse sWAT by exposure to
      cold temperatures and analyzed their molecular signatures. RNA sequencing
      followed by whole genome-wide expression analysis shows that beige adipocytes
      induced from bat aWAT, rather than sWAT, have molecular signatures resembling
      those of mouse sWAT-induced beige adipocytes and exhibit dynamic profiles similar
      to those of classical brown adipocytes. In addition, we identified molecular
      markers that were highly enriched in beige adipocytes and conserved between bat
      aWAT and mouse sWAT, a set that included the genes Uqcrc1 and Letm1. Furthermore,
      knockdown of Uqcrc1 and Letm1 expression shows that they are required not only
      for beige adipocyte differentiation but also for preadipocyte maturation. This
      study presents a new model for research into the induction of beige adipocytes
      from aWAT in vivo, which, when combined with models where beige adipocytes are
      induced from sWAT, provides insight into therapeutic approaches for combating
      obesity-related diseases in humans.

PMID- 30116777
TI  - The intensification of the water footprint of hydraulic fracturing.
AB  - Unconventional oil and gas exploration in the United States has experienced a
      period of rapid growth, followed by several years of limited production due to
      falling and low natural gas and oil prices. Throughout this transition, the water
      use for hydraulic fracturing and wastewater production in major shale gas and oil
      production regions has increased; from 2011 to 2016, the water use per well
      increased up to 770%, while flowback and produced water volumes generated within
      the first year of production increased up to 1440%. The water-use intensity (that
      is, normalized to the energy production) increased ubiquitously in all U.S. shale
      basins during this transition period. The steady increase of the water footprint
      of hydraulic fracturing with time implies that future unconventional oil and gas
      operations will require larger volumes of water for hydraulic fracturing, which
      will result in larger produced oil and gas wastewater volumes.

PMID- 30116776
TI  - Synthetic matrix enhances transplanted satellite cell engraftment in dystrophic
      and aged skeletal muscle with comorbid trauma.
AB  - Muscle satellite cells (MuSCs) play a central role in muscle regeneration, but
      their quantity and function decline with comorbidity of trauma, aging, and muscle
      diseases. Although transplantation of MuSCs in traumatically injured muscle in
      the comorbid context of aging or pathology is a strategy to boost muscle
      regeneration, an effective cell delivery strategy in these contexts has not been
      developed. We engineered a synthetic hydrogel-based matrix with optimal
      mechanical, cell-adhesive, and protease-degradable properties that promotes MuSC
      survival, proliferation, and differentiation. Furthermore, we establish a
      biomaterial-mediated cell delivery strategy for treating muscle trauma, where
      intramuscular injections may not be applicable. Delivery of MuSCs in the
      engineered matrix significantly improved in vivo cell survival, proliferation,
      and engraftment in nonirradiated and immunocompetent muscles of aged and
      dystrophic mice compared to collagen gels and cell-only controls. This platform
      may be suitable for treating craniofacial and limb muscle trauma, as well as
      postoperative wounds of elderly and dystrophic patients.

PMID- 30116778
TI  - A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of
      Parkinson's disease and schizophrenia.
AB  - Individuals with chromosome 22q11.2 deletions are at increased risk of developing
      psychiatric conditions, most notably, schizophrenia (SZ). Recently, clinical
      studies have also implicated these recurrent 22q11.2 deletions with the risk of
      early-onset Parkinson's disease (PD). Thus far, the multiple mouse models
      generated for 22q11.2 deletions have been studied primarily in the context of
      congenital cardiac, neurodevelopmental, and psychotic disorders. One of these is
      the Df1/+ model, in which SZ-associated and developmental abnormalities have been
      reported. We present the first evidence that the mouse model for the 22q11.2
      deletion exhibits motor coordination deficits and molecular signatures (that is,
      elevated alpha-synuclein expression) relevant to PD. Reducing the alpha-synuclein
      gene dosage in Df1/+ mice ameliorated the motor deficits. Thus, this model of the
      22q11.2 deletion shows signatures of both SZ and PD at the molecular and
      behavioral levels. In addition, both SZ-associated and PD-relevant deficits in
      the model were ameliorated by treatment with a rapamycin analog, CCI-779. We now
      posit the utility of 22q11.2 deletion mouse models in investigating the
      mechanisms of SZ- and PD-associated manifestations that could shed light on
      possible common pathways of these neuropsychiatric disorders.

PMID- 30116779
TI  - Annual radiocarbon record indicates 16th century BCE date for the Thera eruption.
AB  - The mid-second millennium BCE eruption of Thera (Santorini) offers a critically
      important marker horizon to synchronize archaeological chronologies of the
      Aegean, Egypt, and the Near East and to anchor paleoenvironmental records from
      ice cores, speleothems, and lake sediments. Precise and accurate dating for the
      event has been the subject of many decades of research. Using calendar-dated tree
      rings, we created an annual resolution radiocarbon time series 1700-1500 BCE to
      validate, improve, or more clearly define the limitations for radiocarbon
      calibration of materials from key eruption contexts. Results show an offset from
      the international radiocarbon calibration curve, which indicates a shift in the
      calibrated age range for Thera toward the 16th century BCE. This finding sheds
      new light on the long-running debate focused on a discrepancy between radiocarbon
      (late 17th-early 16th century BCE) and archaeological (mid 16th-early 15th
      century BCE) dating evidence for Thera.

PMID- 30116780
TI  - A modest 0.5-m rise in sea level will double the tsunami hazard in Macau.
AB  - Rising sea levels will have overwhelmingly negative impacts on coastal
      communities globally. With previous research focused on how sea-level rise (SLR)
      affects storm-induced flooding, we show that SLR will also increase both the
      frequency and the intensity of tsunami-induced flooding, another significant
      coastal hazard associated with sea-level extremes. We developed probabilistic
      tsunami inundation maps for Macau, a densely populated coastal city located in
      the South China Sea, under current sea-level, 0.5-m SLR, and 1-m SLR conditions,
      using an extensive Monte Carlo tsunami inundation simulation. Our results
      indicate that conservative amounts of SLR of 0.5 m (by 2060) and 1 m (by 2100)
      would dramatically increase the frequency of tsunami-induced flooding incidences
      by a factor of 1.2 to 2.4 and 1.5 to 4.7, respectively.

PMID- 30116781
TI  - Fake legal logging in the Brazilian Amazon.
AB  - Declining deforestation rates in the Brazilian Amazon are touted as a
      conservation success, but illegal logging is a problem of similar scale. Recent
      regulatory efforts have improved detection of some forms of illegal logging but
      are vulnerable to more subtle methods that mask the origin of illegal timber. We
      analyzed discrepancies between estimated timber volumes of the national forest
      inventory of Brazil and volumes of logging permits as an indicator of potential
      fraud in the timber industry in the eastern Amazon. We found a strong
      overestimation bias of high-value timber species volumes in logging permits.
      Field assessments confirmed fraud for the most valuable species and complementary
      strategies to generate a "surplus" of licensed timber that can be used to
      legalize the timber coming from illegal logging. We advocate for changes to the
      logging control system to prevent overexploitation of Amazonian timber species
      and the widespread forest degradation associated with illegal logging.

PMID- 30116782
TI  - DNA methylation regulates transcriptional homeostasis of algal endosymbiosis in
      the coral model Aiptasia.
AB  - The symbiotic relationship between cnidarians and dinoflagellates is the
      cornerstone of coral reef ecosystems. Although research has focused on the
      molecular mechanisms underlying this symbiosis, the role of epigenetic
      mechanisms, that is, the study of heritable changes that do not involve changes
      in the DNA sequence, is unknown. To assess the role of DNA methylation in the
      cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation,
      histone associations, and transcriptomic states of symbiotic and aposymbiotic
      anemones in the model system Aiptasia. We found that methylated genes are marked
      by histone 3 lysine 36 trimethylation (H3K36me3) and show significant reduction
      of spurious transcription and transcriptional noise, revealing a role of DNA
      methylation in the maintenance of transcriptional homeostasis. Changes in DNA
      methylation and expression show enrichment for symbiosis-related processes, such
      as immunity, apoptosis, phagocytosis recognition, and phagosome formation, and
      reveal intricate interactions between the underlying pathways. Our results
      demonstrate that DNA methylation provides an epigenetic mechanism of
      transcriptional homeostasis that responds to symbiosis.

PMID- 30116783
TI  - Impacts of forests on children's diet in rural areas across 27 developing
      countries.
AB  - Micronutrient deficiency affects about a third of the world's population.
      Children in developing countries are particularly vulnerable. Consequences
      include impaired cognitive and physical development and increased childhood
      morbidity and mortality. Recent studies suggest that forests help alleviate
      micronutrient deficiency by increasing dietary diversity. However, evidence is
      mostly based on weakly designed local case studies of limited relevance to global
      policies. Furthermore, impacts of forests on diet vary among communities, and
      understanding this variation can help target actions to enhance impact. We
      compile data on children's diets in over 43,000 households across 27 developing
      countries to examine the impacts of forests on dietary diversity. We use
      empirical designs that are attentive to assumptions necessary for causal
      interpretations and that adequately account for confounding factors that could
      mask or mimic the impact. We find that high exposure to forests causes children
      to have at least 25% greater dietary diversity compared to lack of exposure, a
      result comparable to the impacts of some nutrition-sensitive agricultural
      programs. A closer look at a subset of African countries indicates that impacts
      are generally higher for less developed communities, but highest with certain
      access to markets, roads, and education. Our results also indicate that forests
      could help reduce vitamin A and iron deficiencies. Our study establishes the
      causal relationship between forests and diet and thus strengthens the evidence
      for integrating forest conservation and management into nutrition interventions.
      Our results also suggest that providing households some access to capital can
      increase the impact of forest-related interventions on nutrition.

PMID- 30116784
TI  - Cross-disciplinary evolution of the genomics revolution.
AB  - Born out of the Human Genome Project (HGP), the field of genomics evolved with
      phenomenal speed into a dominant scientific and business force. While other
      efforts were intent on estimating the economic impact of the genomics revolution,
      we shift focus to the social and cultural capital generated by bridging together
      biology and computing-two of the constitutive disciplines of "genomics". We
      quantify this capital by measuring the pervasiveness of bio-computing cross
      disciplinarity (XD) in genomics research during and after the HGP. To provide
      interlocking perspectives at the career and epistemic levels, we assembled three
      data sets to measure XD via (i) the collaboration network between 4190 biology
      and computing faculty from 155 departments in the United States, (ii) cross
      departmental affiliations within a comprehensive set of human genomics
      publications, and (iii) the application of computational concepts and methods in
      research published in a preeminent genomics journal. Our results show the
      following: First, research featuring XD collaborations has higher citation impact
      than other disciplinary research-an effect observed at both the career and
      individual article levels. Second, genomics articles featuring XD methods tend to
      have higher citation impact than epistemically pure articles. Third, XD
      researchers of computing pedigree are drawn to the biology culture. This
      statistical evidence acquires deeper meaning when viewed against the
      organizational and knowledge transfer mechanisms revealed by the data models.
      With cross-disciplinary initiatives set to dominate the agenda of funding
      agencies, our case study provides a framework for appreciating the long-term
      effects of these initiatives on science and its standard-bearers.

PMID- 30116785
TI  - Deep fluid pathways beneath Mammoth Mountain, California, illuminated by
      migrating earthquake swarms.
AB  - Although most volcanic seismicity is shallow (within several kilometers of the
      surface), some volcanoes exhibit deeper seismicity (10 to 30+ km) that may
      reflect active processes such as magma resupply and volatile transfer. One such
      volcano is Mammoth Mountain, California, which has also recently exhibited high
      rates of CO2 discharge at the surface. We perform high-resolution earthquake
      detection and relocation to reveal punctuated episodes of rapidly propagating
      seismicity at mid-crustal depths along a narrow fracture zone surrounding a body
      of partial melt. We infer that these earthquakes track dike intrusions or fluid
      pressure pulses associated with CO2 exsolution, suggesting that the deep plumbing
      system of Mammoth Mountain is an active conduit for fluid transport from the base
      of the crust to the surface.

PMID- 30116786
TI  - Genetic regulation of mitotic competence in G0 quiescent cells.
AB  - Quiescent (G0 phase) cells must maintain mitotic competence (MC) to restart the
      cell cycle. This is essential for reproduction in unicellular organisms and also
      for development and cell replacement in higher organisms. Recently, suppression
      of MC has gained attention as a possible therapeutic strategy for cancer. Using a
      Schizosaccharomyces pombe deletion-mutant library, we identified 85 genes
      required to maintain MC during the G0 phase induced by nitrogen deprivation. G0
      cells must recycle proteins and RNA, governed by anabolism, catabolism,
      transport, and availability of small molecules such as antioxidants. Protein
      phosphatases are also essential to maintain MC. In particular, Nem1-Spo7 protects
      the nucleus from autophagy by regulating Ned1, a lipin. These genes, designated
      GZE (G-Zero Essential) genes, reveal the landscape of genetic regulation of MC.

PMID- 30116787
TI  - Mechanism of calmodulin inactivation of the calcium-selective TRP channel TRPV6.
AB  - Calcium (Ca2+) plays a major role in numerous physiological processes. Ca2+
      homeostasis is tightly controlled by ion channels, the aberrant regulation of
      which results in various diseases including cancers. Calmodulin (CaM)-mediated
      Ca2+-induced inactivation is an ion channel regulatory mechanism that protects
      cells against the toxic effects of Ca2+ overload. We used cryo-electron
      microscopy to capture the epithelial calcium channel TRPV6 (transient receptor
      potential vanilloid subfamily member 6) inactivated by CaM. The TRPV6-CaM complex
      exhibits 1:1 stoichiometry; one TRPV6 tetramer binds both CaM lobes, which adopt
      a distinct head-to-tail arrangement. The CaM carboxyl-terminal lobe plugs the
      channel through a unique cation-pi interaction by inserting the side chain of
      lysine K115 into a tetra-tryptophan cage at the pore's intracellular entrance. We
      propose a mechanism of CaM-mediated Ca2+-induced inactivation that can be
      explored for therapeutic design.

PMID- 30116788
TI  - Holistic Assessment of Rumen Microbiome Dynamics through Quantitative
      Metatranscriptomics Reveals Multifunctional Redundancy during Key Steps of
      Anaerobic Feed Degradation.
AB  - Ruminant livestock is a major source of the potent greenhouse gas methane. The
      complex rumen microbiome, consisting of bacteria, archaea, and microbial
      eukaryotes, facilitates anaerobic plant biomass degradation in the cow rumen,
      leading to methane emissions. Using an integrated approach combining multidomain
      quantitative metatranscriptomics with gas and volatile fatty acid (VFA)
      profiling, we aimed at obtaining the most comprehensive picture of the active
      rumen microbiome during feed degradation to date. Bacterial, archaeal, and
      eukaryotic biomass, but also methane emissions and VFA concentrations, increased
      drastically within an hour after feed intake. mRNA profiling revealed a dynamic
      response of carbohydrate-active enzyme transcripts, transcripts involved in VFA
      production and methanogenesis. While the relative abundances of functional
      transcripts did not mirror observed processes, such as methane emissions,
      transformation to mRNA abundance per gram of rumen fluid echoed ruminant
      processes. The microbiome composition was highly individual, with, e.g., ciliate,
      Neocallimastigaceae, Prevotellaceae, Succinivibrionaceae, and Fibrobacteraceae
      abundances differing between cows. Microbiome individuality was accompanied by
      inter- and intradomain multifunctional redundancy among microbiome members during
      feed degradation. This likely enabled the robust performance of the anaerobic
      degradation process in each rumen. Neocallimastigaceae and ciliates contributed
      an unexpectedly large share of transcripts for cellulose- and hemicellulose
      degrading enzymes, respectively. Methyl-reducing but not CO2-reducing methanogens
      were positively correlated with methane emissions. While Methanomassiliicoccales
      switched from methanol to methylamines as electron acceptors, Methanosphaera
      became the dominating methanol-reducing methanogen. This study for the first time
      linked rumen meta-omics with processes and enabled holistic insights into the
      contribution of all microbiome members to feed degradation. IMPORTANCE Ruminant
      animals, such as cows, live in a tight symbiotic association with microorganisms,
      allowing them to feed on otherwise indigestible plant biomass as food sources.
      Methane is produced as an end product of the anaerobic feed degradation in
      ruminants and is emitted to the atmosphere, making ruminant animals among the
      major anthropogenic sources of the potent greenhouse gas methane. Using newly
      developed quantitative metatranscriptomics for holistic microbiome analysis, we
      here identified bacterial, archaeal, and eukaryotic key players and the short
      term dynamics of the rumen microbiome during anaerobic plant biomass degradation
      and subsequent methane emissions. These novel insights might pave the way for
      novel ecologically and economically sustainable methane mitigation strategies,
      much needed in times of global climate change.

PMID- 30116790
TI  - Translation of a community palliative care intervention: Experience from West
      Bengal, India.
AB  - Background: The community form of palliative care first constructed in Kerala,
      India has gained recognition worldwide. Although it is the subject of important
      claims about its replicability elsewhere, little effort has gone into studying
      how this might occur. Drawing on translation studies, we attend to under-examined
      aspects of the transfer of a community palliative care intervention into a new
      geographic and institutional context. Methods: Over a period of 29 months, we
      conducted an in-depth case study of Sanjeevani, a community-based palliative care
      organization in Nadia district, West Bengal (India), that is modelled on the
      Kerala approach. We draw upon primary (semi-structured interviews and field
      notes) and secondary data sources. Results: We identify the translator's symbolic
      power and how it counteracts the organizational challenges relating to socio
      economic conditions and weak histories of civil society organizing. We find that
      unlike the Kerala form, which is typified by horizontal linkages and consensus
      oriented decision-making, the translated organizational form in Nadia is a hybrid
      of horizontal and vertical solidarities. We show how translation is an ongoing,
      dynamic process, where community participation is infused with values of
      occupational prestige and camaraderie and shaped by emergent vertical
      solidarities among members. Conclusions: Our findings have implications for how
      we understand the relationship between locations, institutional histories, and
      healthcare interventions. We contribute to translation studies in healthcare, and
      particularly to conversations about the transfer or 'roll out' of palliative care
      interventions from one geography to another.

PMID- 30116789
TI  - Genomic Characterization and Copy Number Variation of Bacillus anthracis Plasmids
      pXO1 and pXO2 in a Historical Collection of 412 Strains.
AB  - Bacillus anthracis plasmids pXO1 and pXO2 carry the main virulence factors
      responsible for anthrax. However, the extent of copy number variation within the
      species and how the plasmids are related to pXO1/pXO2-like plasmids in other
      species of the Bacillus cereus sensu lato group remain unclear. To gain new
      insights into these issues, we sequenced 412 B. anthracis strains representing
      the total phylogenetic and ecological diversity of the species. Our results
      revealed that B. anthracis genomes carried, on average, 3.86 and 2.29 copies of
      pXO1 and pXO2, respectively, and also revealed a positive linear correlation
      between the copy numbers of pXO1 and pXO2. No correlation between the plasmid
      copy number and the phylogenetic relatedness of the strains was observed.
      However, genomes of strains isolated from animal tissues generally maintained a
      higher plasmid copy number than genomes of strains from environmental sources (P
      < 0.05 [Welch two-sample t test]). Comparisons against B. cereus genomes carrying
      complete or partial pXO1-like and pXO2-like plasmids showed that the plasmid
      based phylogeny recapitulated that of the main chromosome, indicating limited
      plasmid horizontal transfer between or within these species. Comparisons of gene
      content revealed a closed pXO1 and pXO2 pangenome; e.g., plasmids encode <8
      unique genes, on average, and a single large fragment deletion of pXO1 in one B.
      anthracis strain (2000031682) was detected. Collectively, our results provide a
      more complete view of the genomic diversity of B. anthracis plasmids, their copy
      number variation, and the virulence potential of other Bacillus species carrying
      pXO1/pXO2-like plasmids. IMPORTANCE Bacillus anthracis microorganisms are of
      historical and epidemiological importance and are among the most homogenous
      bacterial groups known, even though the B. anthracis genome is rich in mobile
      elements. Mobile elements can trigger the diversification of lineages; therefore,
      characterizing the extent of genomic variation in a large collection of strains
      is critical for a complete understanding of the diversity and evolution of the
      species. Here, we sequenced a large collection of B. anthracis strains (>400)
      that were recovered from human, animal, and environmental sources around the
      world. Our results confirmed the remarkable stability of gene content and synteny
      of the anthrax plasmids and revealed no signal of plasmid exchange between B.
      anthracis and pathogenic B. cereus isolates but rather predominantly vertical
      descent. These findings advance our understanding of the biology and pathogenomic
      evolution of B. anthracis and its plasmids.

PMID- 30116791
TI  - Smartphones for community health in rural Cambodia: A feasibility study.
AB  - Background: Village Malaria Workers (VMWs) are lay people trained to provide a
      valuable role in frontline testing and treatment of malaria in rural villages in
      Cambodia. Emergence of artemisinin-resistant malaria highlights the essential
      role of such VMWs in surveillance and early treatment of malaria. Smartphone
      technology offers huge potential to support VMWs in isolated and resource-poor
      settings.  Methods: We investigated the feasibility of issuing established VMWs
      with a smartphone, bespoke Android application and solar charger to support their
      role. 27 VMWs in Kampong Cham and Kratie provinces participated.  Results: 26/27
      of the smartphones deployed were working well at study completion twelve months
      later. Interviews with VMWs using quantitative and qualitative methods revealed
      pride, ease of use and reports of faster communication with the smartphone. VMWs
      also expressed a strong wish to help people presenting with non-malarial fever,
      for which further potential supportive smartphone applications are increasingly
      available.  Conclusions: As a result of this pilot study, two smartphone based
      reporting systems for malaria have been developed at the Cambodian National
      Malaria Center, and the programme is now being extended nationwide. The full code
      for the smartphone application is made available to other researchers and
      healthcare providers with this article. Smartphones represent a feasible platform
      for developing the VMW role to include other health conditions, thus maintaining
      the relevance of these important community health workers.

PMID- 30116792
TI  - Can paediatric emergency clinicians identify and manage clavicle fractures
      without radiographs in the emergency department? A prospective study.
AB  - Background: Paediatric clavicle fractures are commonly seen in the emergency
      department (ED), and the current standard of care is to obtain a radiograph for
      all suspected clavicle fractures. We are yet to determine whether radiographs add
      valuable information to clinicians' assessment and therefore if they are
      necessary in the management of paediatric clavicle fractures. Objective: To
      determine whether clinicians can manage paediatric clavicle fractures without
      radiographs, first by determining the accuracy of clinicians in identifying the
      presence of a clavicle fracture, and second by evaluating the level of agreement
      (kappa (kappa)) between the ultimate management of children with suspected
      clavicle fractures and clinicians' blinded prediction prior to the radiograph.
      Methods: This prospective study enrolled patients presenting to a paediatric ED
      with a suspected clavicle fracture. Prior to requesting a radiograph, clinicians
      completed a standardised form, where they predicted the presence of a fracture
      and their ultimate management based on their clinical findings, and rated their
      confidence. Results: Of the 50 patients aged 7.2+/-3.9 years included, 40 (80%)
      had a radiologically proven clavicle fracture, and clinicians were able to
      accurately identify them (sensitivity 93%, positive predictive value 88%). There
      were five (50%) patients without a radiological fracture that were treated with
      broad arm sling. Clinicians' prediction of ultimate management had the highest
      agreement with the ultimate management of the patient on leaving the ED, compared
      with clinicians' prediction of the presence of fracture and the final radiograph
      findings: kappa of 0.88 (95% CI 0.64 to 1), 0.67 (95% CI 0.36 to 0.98) and 0.62
      (95% CI 0.30 to 0.94), respectively. Thirty-six (72%) of the clinicians felt
      comfortable treating without radiographs, and this was dependent on their level
      of training. Conclusions: Clinicians can identify the presence of a fracture and
      tend to be overconservative in their management. Despite negative radiological
      findings, some patients were treated as though they had a fracture, based on
      clinical judgement. This adds evidence that radiographs are not routinely
      required for uncomplicated paediatric clavicle fractures.

PMID- 30116793
TI  - Salivary beta-endorphin and substance P are not biomarkers of neuropathic chronic
      pain propensity.
AB  - Objective: The pathophysiology of chronic pain is complex, with most of our
      knowledge being derived from preclinical studies. The search for biomarkers
      mirroring the pathophysiology of chronic pain is ongoing, and there is an
      increasing interest in saliva as a diagnostic tool. Given what is known about
      salivary substance P and salivary gland innervation, we hypothesized that
      salivary substance P and/or beta-endorphin might reflect the basal activity of
      these neuropeptides in the central nervous system, thereby perhaps mirroring a
      general propensity to chronic pain. Based on this overall hypothesis, our aim was
      to compare salivary levels of these neuropeptides in chronic neuropathic pain
      patients with healthy controls. An additional aim was to relate salivary levels
      to plasma levels. Materials and methods: We compared salivary concentrations of
      beta-endorphin and substance P in 14 chronic neuropathic pain patients with
      concentrations in 18 healthy controls using a Luminex technology kit. Salivary-to
      plasma quotients were also calculated. Results: We found no significant
      difference between the groups' salivary concentrations of substance P and beta
      endorphin. No correlation was found between salivary and plasma concentrations of
      each neuropeptide, which we hypothesize might point to local production of beta
      endorphin and/or substance P in the salivary glands. Given high substance P
      salivary-to-plasma quotients, such a local production seems more likely for
      substance P than for beta-endorphin. Conclusions: Propensity to neuropathic
      chronic pain was not substantiated by our analysis of salivary levels of
      substance P and/or beta-endorphin. However, we report salivary-to-plasma
      quotients that give potentially important physiological insight about these
      neuropeptides.

PMID- 30116795
TI  - Effect of Combined Gluten-Free, Dairy-Free Diet in Children With Steroid
      Resistant Nephrotic Syndrome: An Open Pilot Trial.
AB  - Introduction: Steroid-resistant nephrotic syndrome (SRNS) affects both children
      and adults and has a high rate of progression to end-stage renal disease.
      Although a subset of patients have well-characterized genetic mutation(s), in the
      majority of cases, the etiology is unknown. Over the past 50 years, a number of
      case reports have suggested the potential impact of dietary changes in
      controlling primary nephrotic syndrome, especially gluten and dairy restrictions.
      Methods: We have designed a prospective, open-label, nonrandomized, pilot
      clinical trial, to study the effect of a gluten-free and dairy-free (GF/DF) diet
      in children with SRNS. The study will be organized as a 4-week summer camp to
      implement a GF/DF diet in a tightly controlled and monitored setting. Blood,
      urine, and stool samples will be collected at different time points during the
      study. Results: The primary end point is a reduction of more than 50% in the
      urine protein:creatinine ratio. The secondary end points include changes in urine
      protein, kidney function, and serum albumin, as well as effects in immune
      activation, kidney injury biomarkers, and gut microbiome composition and function
      (metagenomic/metatranscriptomic). Conclusion: This study will advance the field
      by testing the effect of dietary changes in patients with SRNS in a highly
      controlled camp environment. In addition, we hope the results will help to
      identify a responder profile that may guide the design of a larger trial for
      further investigation.

PMID- 30116794
TI  - Fusobacterium nucleatum Infection in Colorectal Cancer: Linking Inflammation, DNA
      Mismatch Repair and Genetic and Epigenetic Alterations.
AB  - It has been recently reported that the population of Fusobacterium, particularly
      Fusobacterium nucleatum (Fn), is overrepresented in colorectal cancers and
      adenomas. The promoting effects of Fn infection on adenoma and/or carcinoma
      formation have been shown in ApcMin/+mice. Characteristics of Fn-associated CRC
      were identified through studies using human CRC cohorts, and include right-sided
      colon location, CpG island methylation phenotype-high (CIMP-H), high level of
      microsatellite instability (MSI-H), and poor patient prognosis. A subset of Fn
      associated CRC exhibits a low level of microsatellite instability (MSI-L) and
      elevated microsatellite alterations in selected tetra-nucleotide repeats (EMAST)
      induced by translocation of MSH3 from the nucleus to the cytoplasm in response to
      oxidative DNA damage or inflammatory signals. The association between CIMP/MSI-H
      and Fn-infection can be explained by the role of the mismatch repair (MMR)
      protein complex formed between MSH2 and MSH6 (MutSalpha) to repair aberrant bases
      generated by ROS to form 7,8-dihydro-8-oxo-guanine (8-oxoG). Clustered 8-oxoGs
      formed at CpG-rich regions including promoters by ROS is refractory to base
      excision repair (BER). Under these conditions, MutSalpha initiates repair in
      cooperation with DNA methyltransferases (DNMTs) and the polycomb repressive
      complex 4 (PRC4). DNMTs at damaged sites methylate CpG islands to repress
      transcription of target genes and promote repair reactions. Thus, continuous
      generation of ROS through chronic Fn infection may initiate 1) CIMP-positive
      adenoma and carcinoma in an MSH2/MSH6-dependent manner, and/or 2) MSI-L/EMAST CRC
      in an MSH3-dependent manner. The poor prognosis of Fn-associated CRC can be
      explained by Fn-induced immune-evasion and/or chemo-resistance.

PMID- 30116797
TI  - The Psychophysics of Algebra Expertise: Mathematics Perceptual Learning
      Interventions Produce Durable Encoding Changes.
AB  - Mathematics requires thinking but also pattern recognition. Recent research
      indicates that perceptual learning (PL) interventions facilitate discovery of
      structure and recognition of patterns in mathematical domains, as assessed by
      tests of mathematical competence. Here we sought direct evidence that a brief
      perceptual learning module (PLM) produces changes in basic information
      extraction. Accuracy and speed of undergraduate participants' encoding of
      equations was assessed in a psychophysical task at pretest and delayed posttest.
      In between, the experimental group completed an Algebraic Transformations PLM,
      which involved identifying valid transformations of equations. Relative to
      controls, PLM participants showed reliable changes in encoding equations,
      detectable psychophysically 24 hours later. Encoding improvements were shown
      robustly by participants who were initially less proficient at algebra and were
      negligible for participants who were initially proficient. These results provide
      direct evidence for durable changes in information encoding produced by a PL
      intervention targeting a complex mathematical skill.

PMID- 30116796
TI  - Fluorescence Lifetime Imaging Ophthalmoscopy: A Novel Way to Assess Macular
      Telangiectasia Type 2.
AB  - Purpose: Macular Telangiectasia Type 2 (MacTel) is an uncommon, late-onset
      complex retinal disease that leads to central vision loss. No causative gene(s)
      have been identified so far, resulting in a challenging clinical diagnostic
      dilemma because retinal changes of early stages are often subtle. The objective
      of this study was to investigate the benefit of fluorescence lifetime imaging
      ophthalmoscopy (FLIO) for retinal imaging in patients with MacTel. Design: Cross
      sectional study from a tertiary-care retinal referral practice. Subjects and
      Controls: 42 eyes of 21 patients (mean age 60.5+/-13.3 years) with MacTel as well
      as an age-matched healthy control group (42 eyes of 25 subjects, mean age 60.8+/
      13.4 years). Methods: A 30 degrees  retinal field centered at the fovea was
      investigated using FLIO. This camera is based on a Heidelberg Engineering
      Spectralis system. Fundus autofluorescence (FAF) decays were detected in short
      (498-560 nm, SSC) and long (560-720 nm, LSC) spectral channels. The mean
      fluorescence lifetime, taum, was calculated from a 3-exponential approximation of
      the FAF decays. For MacTel patients, macular pigment (MP), OCT, blue light
      reflectance, fluorescein angiography, as well as fundus photography, were also
      recorded. Main Outcome Measures: Mean FAF lifetime (taum) images. Results: FLIO
      of MacTel patients shows a unique pattern of prolonged taum at the temporal side
      of the fovea in patients with MacTel in the "MacTel area" within 5-6 degrees  of
      the foveal center. In early stages, this region appears crescent-shaped, while
      advanced stages show a ring-like pattern. This pattern corresponds well with
      other imaging modalities and gives an especially high contrast of the affected
      region even in minimally affected individuals. Additionally, FLIO provides a
      novel means to monitor the abnormal MP distribution. In one case, FLIO showed
      changes suggestive of MacTel within a clinically normal parent of two MacTel
      patients. Conclusions: FLIO detects retinal changes in patients with MacTel with
      high contrast, presenting a distinctive signature that is a characteristic
      finding of the disease. The non-invasive properties of this novel imaging
      modality provide a valuable addition to clinical assessment of early changes in
      the disease that could lead to more accurate diagnosis of MacTel.

PMID- 30116798
TI  - Styrylsilane coupling reagents for immobilization of organic functional groups on
      silica and glass surfaces.
AB  - Styrylsilanes serve as new coupling reagents for introducing organic functional
      groups on silica and glass surfaces. Functionalized styrylsilanes, which are
      readily prepared via catalytic hydrosilylation of the corresponding
      phenylacetylenes with silanes, are immobilized on silica through acid catalyzed
      processes under mild conditions.

PMID- 30116799
TI  - Hexagonal Ti2B2 monolayer: a promising anode material offering high rate
      capability for Li-ion and Na-ion batteries.
AB  - Combining the first-principles density functional method and crystal structure
      prediction techniques, we report a series of hexagonal two-dimensional transition
      metal borides including Sc2B2, Ti2B2, V2B2, Cr2B2, Y2B2, Zr2B2, and Mo2B2. Their
      dynamic and thermal stabilities are testified by phonon and molecular dynamics
      simulations. We investigate the potential of the two-dimensional Ti2B2 monolayer
      as an anode material for Li-ion and Na-ion batteries. The Ti2B2 monolayer
      possesses high theoretical specific capacities of 456 and 342 mA h g-1 for Li and
      Na, respectively. The very high Li/Na diffusivity with an ultralow energy barrier
      of 0.017/0.008 eV indicates an excellent charge-discharge capability. In
      addition, good electronic conductivity during the whole lithiation process is
      found by electronic structure calculations. The very small change in volume after
      the adsorption of one, two, and three layers of Li and Na ions indicates that the
      Ti2B2 monolayer is robust. These results highlight the suitability of Ti2B2
      monolayer as well as the other two-dimensional transition metal borides as
      excellent anode materials for both Li-ion and Na-ion batteries.

PMID- 30116800
TI  - Single particle study: size and chemical effects on plasmon damping at the
      interface between adsorbate and anisotropic gold nanorods.
AB  - Plasmon damping in gold nanorods (AuNRs) results in the broadening of the
      localized surface plasmon resonance (LSPR) linewidth. LSPR broadening of
      plasmonic nanoparticles is useful to maximize the fraction of light energy in
      light harvesting and energy conversion transferred to molecules attached on the
      surface. However, our understanding of plasmon decay channels in AuNRs is still
      limited, and chemical interface damping (CID) is the most poorly understood
      damping mechanism. Herein, to better understand plasmon damping including CID, we
      performed a single particle study of plasmonic anisotropic AuNRs using dark-field
      (DF) microscopy and spectroscopy. First, we examined the size-dependent
      broadening of the homogeneous LSPR linewidth of single AuNRs in water with three
      different aspect ratios (ARs) at a fixed diameter of 25 nm. The LSPR linewidth
      increased with a decrease in the AR of single AuNRs because of the reduced
      average distance of hot electrons to the surface. Second, we investigated the
      effect of refractive index variation of the surrounding medium on the LSPR
      linewidth in single AuNRs of three different sizes. The LSPR linewidth in single
      AuNRs remained almost constant regardless of their sizes while increasing the
      dielectric constant of the medium. Finally, we examined the effect of adsorbate
      thiol molecules on the homogeneous LSPR linewidth of single AuNRs in ethanol. The
      LSPR linewidth was broadened upon increasing the carbon chain length of 1
      alkanethiol, and 4-nitrothiophenol with a strong electron withdrawing group
      induced a large broadening of the LSPR linewidth. Furthermore, single AuNRs with
      smaller ARs showed a larger broadening of the LSPR linewidth in the presence of
      adsorbate thiol molecules through CID. Therefore, this investigation provides a
      deeper insight into the size effect on plasmon damping including CID induced by
      the chemical interface effect in single AuNRs.

PMID- 30116801
TI  - Effect of alkali ions on optical properties of flavins: vibronic spectra of
      cryogenic M+lumichrome ions (M = Li-Cs) in the gas phase.
AB  - The photochemical properties of flavins depend sensitively on their environment
      and are strongly modified by coordination with metal ions. Herein, the electronic
      spectra of cold complexes of the smallest flavin molecule (lumichrome, LC,
      C12N4O2H10) with alkali ions (M+LC, M = Li-Cs) are measured by photodissociation
      in the visible range (VISPD) in a cryogenic ion trap coupled to a tandem mass
      spectrometer and an electrospray ionization source. The observed vibronic spectra
      of all ions are assigned to the optically bright S1 <- S0 (pipi*) transition of
      the most stable O4 isomer of M+LC by comparison with quantum chemical
      calculations at the PBE0/cc-pVDZ level coupled to multidimensional Franck-Condon
      simulations. The rich vibronic spectra indicate substantial geometry changes upon
      S1 excitation. Large red shifts of the S1 origins upon metal complexation and
      progressions in the intermolecular in-plane metal stretch and bend modes
      demonstrate that the strength of the metal-flavin interaction in M+LC(O4)
      strongly increases by S1 excitation. The stronger M+LC bond in the S1 state of
      M+LC(O4) is rationalized by the charge reorganization upon pipi* excitation of
      the LC chromophore. The computations confirm that the optical properties of LC
      can be strongly modulated by metalation via both the type and binding site of the
      metal ion.

PMID- 30116802
TI  - Experimental strategies for 13C-15N dipolar NMR spectroscopy in liquid crystals
      at the natural isotopic abundance.
AB  - Direct dipolar spin couplings are informative and sensitive probes for a wide
      range of dynamic processes and structural properties at atomic, molecular and
      supramolecular levels in liquid crystals and other anisotropic materials.
      Usually, heteronuclear 13C-1H dipolar couplings in liquid crystals with natural
      13C abundance are measured. Recording 13C-15N NMR dipolar spectra in unlabeled
      materials is challenging because of the unfavorable combination of two rare
      isotopes. Here we design and compare various experimental strategies to measure
      short- and long-range heteronuclear 13C-15N dipolar couplings in liquid
      crystalline samples with high molecular orientational order. New techniques were
      developed to record 13C and 15N spectra of naturally occurring 13C-15N spin pairs
      with increased signal intensity and spectral resolution while suppressing the
      signals of the uncoupled isotopes. Highly resolved 13C-15N dipolar spectra were
      recorded within an experimental time of a few hours. Coupling constants in a
      broad range of 10-1000 Hz between spins separated by up to five chemical bonds
      and distances of up to 5 A were measured. Because of their relatively low demands
      on radio-frequency power levels, the experiments were easy to implement using
      conventional high-resolution solution-state NMR hardware. Experimental data were
      compared to the results of density functional theory and molecular dynamics
      computational analyses. The presented experimental methods to characterize the
      dipolar couplings in unlabeled materials provide novel routes to investigate
      molecular structure and dynamics in mesophases.

PMID- 30116803
TI  - Unexpected high binding energy of CO2 on CH3NH3PbI3 lead-halide organic-inorganic
      perovskites via bicarbonate formation.
AB  - The adsorption kinetics of CO2 was experimentally characterized in ultra-high
      vacuum (UHV). Unexpectedly, high desorption temperatures (640 K, 170 kJ mol-1)
      were seen. Density functional theory (DFT) calculations suggest the stabilization
      mechanism: bicarbonate formation in the defected perovskite film due to CO2 and
      H2O coadsorption.

PMID- 30116804
TI  - Diversity-oriented synthesis of chromenopyrrolidines from azomethine ylides and 2
      hydroxybenzylidene indandiones via base-controlled regiodivergent (3+2)
      cycloaddition.
AB  - An organobase-directed, regiodivergent 1,3-dipolar cycloaddition of azomethine
      ylides and 2-hydoxybenzylidene indandiones is reported. The scarcely explored
      reversal of the nucleophilic site in azomethine ylides has been exploited for
      their regiodivergent (3+2) cycloaddition, which subsequently resulted in two
      different cascade processes to generate functionally distinct
      chromenopyrrolidines in a diversity oriented manner.

PMID- 30116805
TI  - Glucose oxidase mediated targeted cancer-starving therapy by biotinylated self
      assembled vesicles.
AB  - Herein, we demonstrate glucose oxidase (GOx) mediated targeted cancer-starving
      therapy by self-assembled vesicle of trimesic acid based biotinylated amphiphile
      (TMB). The TMB vesicles entrapped GOx and selectively killed cancer cells (HeLa,
      B16F10), with ~6-fold higher efficiency compared to non-cancer cells (CHO,
      NIH3T3), by blocking the energy supply to tumors through the oxidation of
      intracellular glucose.

PMID- 30116806
TI  - A photocatalytic iminyl radical-mediated C-C bond cleavage/addition/cyclization
      cascade for the synthesis of 1,2,3,4-tetrahydrophenanthrenes.
AB  - On the basis of the strategy of iminyl radical-mediated C-C bond cleavage, a
      visible light photocatalytic radical addition/cyclization cascade is described,
      providing an efficient and regioselective access to cyanoalkylated 1,2,3,4
      tetrahydrophenanthrenes.

PMID- 30116808
TI  - Palladium-catalyzed direct mono-aroylation of O-arylmethyl and aryl-substituted
      acetoxime ethers.
AB  - An efficient palladium-catalyzed ortho-aroylation of O-arylmethyl and aryl
      substituted acetoxime ethers has been developed; this method has high mono-site
      selectivity and does not require exogenous ligands. Under the direction of a
      simple exo-acetoxime auxiliary, a broad scope of masked arylmethyl alcohols and
      phenols as well as various aromatic aldehydes are compatible with this
      transformation, which probably follows a mechanistic pathway involving a six- or
      five-membered exo-cyclopalladated intermediate. The strategy can be expediently
      adopted to prepare synthetically valuable 1H-benzo[d][1,2]oxazines and
      benzo[d]isoxazoles. The directing group can be easily removed from the products
      to afford the functionalized diaryl ketones.

PMID- 30116807
TI  - On the universality of the flow properties of soft-particle glasses.
AB  - We identify the minimal interparticle interactions necessary for a particle
      dynamics simulation to predict the structure and flow behaviour of soft particle
      glasses (SPGs). Generally, two kinds of forces between the particles must be
      accounted for in simulations of SPGs: viscous or frictional drag forces and
      elastic contact forces. Far field drag forces are required to dissipate energy in
      the simulations and capture the effect of the rheology of the suspending fluid.
      Elastic forces are found to be dominant compared to near-field drag or other
      forms of friction forces and are the most important component to compute the
      rheology. The shear stress, the first and second normal stress differences for
      different interparticle force laws collapse onto universal master curves of the
      Herschel-Bulkley form by non-dimensionalizing the stress with the yield stress
      and the shear rate with the viscosity of the suspending fluid divided by the low
      frequency shear modulus. The Herschel-Bulkley exponents are close to 0.5 with a
      slight dependence on the repulsive pairwise elastic forces.

PMID- 30116809
TI  - Spectroscopy of a rotating hydrogen molecule in carbon nanotubes.
AB  - A first-principles study of the spectroscopy of a single hydrogen molecule
      rotating inside and outside of carbon nanotubes is presented. Density functional
      theory (DFT)-based symmetry-adapted perturbation theory (SAPT) is applied to
      analyze the influence of the rotation in the dispersionless and dispersion energy
      contributions to the adsorbate-nanotube interaction. A potential model for the H2
      nanotube interaction is proposed and applied to derive the molecular energy
      levels of the rotating hydrogen molecule. The SAPT-based analysis shows that a
      subtle balance between the dispersionless and dispersion contributions is key in
      determining the angular dependence of the H2-nanotube interaction, which is
      strongly influenced by the diameter of the carbon nanotubes. As a consequence,
      the structure of molecular energy levels is very different in wide and narrow
      nanotubes with the diameter above and below 1 nanometer, respectively. Strong
      anisotropy effects lead to a rather constrained rotation of molecular hydrogen
      inside narrow nanotubes.

PMID- 30116810
TI  - Triphenylamine derived titanium oxo clusters: an approach to effective organic
      inorganic hybrid dyes for photoactive electrodes.
AB  - Titanium oxo clusters (TOCs) anchored with photoactive triphenylamine (TPA) dyes
      are reported for the first time. The TiO2 electrodes modified with the TPA dye
      pre-anchored TOCs showed excellent photocurrent response properties.

PMID- 30116811
TI  - Tuning transition metal carbide activity by surface metal alloying: a case study
      on CO2 capture and activation.
AB  - CO2 is one of the main actors in the greenhouse effect and its removal from the
      atmosphere is becoming an urgent need. Thus, CO2 capture and storage (CCS) and
      CO2 capture and usage (CCU) are intensively investigated technologies to decrease
      the concentration of atmospheric CO2. Both CCS and CCU require appropriate
      materials to adsorb/release and adsorb/activate CO2, respectively. Recently, it
      has been theoretically and experimentally shown that transition metal carbides
      (TMC) are able to capture, store, and activate CO2. To further improve the
      adsorption capacity of these materials, a deep understanding of the atomic level
      processes involved is essential. In the present work, we theoretically
      investigate the possible effects of surface metal doping of these TMCs by taking
      TiC as a textbook case and Cr, Hf, Mo, Nb, Ta, V, W, and Zr as dopants. Using
      periodic slab models with large supercells and state-of-the-art density
      functional theory based calculations we show that CO2 adsorption is enhanced by
      doping with metals down a group but worsened along the d series. Adsorption
      sites, dispersion and coverage appear to play a minor, secondary constant effect.
      The dopant-induced adsorption enhancement is highly biased by the charge
      rearrangement at the surface. In all cases, CO2 activation is found but doping
      can shift the desorption temperature by up to 135 K.

PMID- 30116812
TI  - Molecularly endowed hydrogel with an in silico-assisted screened peptide for
      highly sensitive small molecule harvesting.
AB  - We present a novel method for the detection of small molecules in complex fluids
      based on the selection of a specific peptide for target capture and its
      integration into an antifouling polymeric network. Such an approach can represent
      a universal platform for the direct and ultra-sensitive detection of small
      molecules in complex media.

PMID- 30116813
TI  - Building of neomycin-nucleobase-amino acid conjugates for the inhibition of
      oncogenic miRNAs biogenesis.
AB  - MicroRNAs (miRNAs) are a recently discovered category of small RNA molecules that
      regulate gene expression at the post-transcriptional level. Accumulating evidence
      indicates that miRNAs are aberrantly expressed in a variety of human cancers,
      thus being oncogenic. The inhibition of oncogenic miRNAs (defined as the blocking
      of miRNAs' production or function) would find application in the therapy of
      different types of cancer in which these miRNAs are implicated. In this work, we
      describe the design and synthesis of new small-molecule RNA ligands with the aim
      of inhibiting Dicer-mediated processing of oncogenic miRNAs. One of the
      synthesized compound (4b) composed of the aminoglycoside neomycin conjugated to
      an artificial nucleobase and to amino acid histidine is able to selectively
      decrease miR-372 levels in gastric adenocarcinoma (AGS) cells and to restore the
      expression of the target LATS2 protein. This activity led to the inhibition of
      proliferation of these cells. The study of the interactions of 4b with pre-miR
      372 allowed for the elucidation of the molecular mechanism of the conjugate, thus
      leading to new perspectives for the design of future inhibitors.

PMID- 30116814
TI  - Development of a ReaxFF reactive force field for lithium ion conducting solid
      electrolyte Li1+xAlxTi2-x(PO4)3 (LATP).
AB  - We developed a ReaxFF reactive force field for NASICON-type Li1+xAlxTi2-x(PO4)3
      (LATP) materials, which is a promising solid-electrolyte that may enable all
      solid-state lithium-ion batteries. The force field parameters were optimized
      based on density functional theory (DFT) data, including equations of state and
      the heats of formation of ternary metal oxides and metal phosphate crystal phases
      (e.g., LixTiO2, Al2TiO5, LiAlO2, AlPO4, Li3PO4 and LiTi2(PO4)3 (LTP)), and the
      energy barriers for Li diffusion in TiO2 and LTP via vacancies and interstitial
      sites. Using ReaxFF, the structural and the energetic features of LATP were
      described properly across various compositions - Li occupies more preferentially
      the interstitial site next to Al than next to Ti. Also, as observed in
      experimental data, the lattice parameters decrease when Ti is partly substituted
      by Al because of the smaller size of the Al cation. Using this force field, the
      diffusion mechanism and the ionic conductivity of Li in LTP and LATP were
      investigated at T = 300-1100 K. Low ionic conductivity (5.9 * 10-5 S cm-1 at 300
      K) was obtained in LTP as previously reported. In LATP at x = 0.2, the ionic
      conductivity was slightly improved (8.4 * 10-5 S cm-1), but it is still below the
      experimental value, which is on the order of 10-4 to 10-3 S cm-1 at x = 0.3-0.5.
      At higher x (higher Al composition), LATP has a configurational diversity due to
      the Al substitution and the concomitant insertion of Li. By performing a hybrid
      MC/MD simulation for LATP at x = 0.5, a thermodynamically stable LATP
      configuration was obtained. The ionic conductivity of this LATP configuration was
      calculated to be 7.4 * 10-4 S cm-1 at 300 K, which is one order of magnitude
      higher than the ionic conductivity for LTP and LATP at x = 0.2. This value is in
      good agreement with our experimental value (2.5 * 10-4 S cm-1 at 300 K) and the
      literature values. The composition-dependent ionic conductivity of LATP was
      successfully demonstrated using the ReaxFF reactive force field, verifying the
      applicability of the LATP force field for the understanding of Li diffusion and
      the design of highly Li ion conductive solid electrolytes. Furthermore, our
      results also demonstrate the feasibility of the MC/MD method in modeling LATP
      configuration, and provide compelling evidence for the solid solution sensitivity
      on ionic conductivity.

PMID- 30116815
TI  - Observing phase transformation in CVD-grown MoS2via atomic resolution TEM.
AB  - We utilized in situ transmission electron microscopy to observe phase
      transformation in CVD-grown MoS2. Significantly, the reaction was performed under
      electron irradiation through appropriate control of the electron dose and
      exposure time. Moreover, we proposed a new route between the 2H and 1T phases
      that involved the higher energy states TS1/TS2.

PMID- 30116816
TI  - Highly selective room temperature acetylene sorption by an unusual triacetylenic
      phosphine MOF.
AB  - The new ligand tris(p-carboxyphenylethynyl)phosphine (P{C[triple bond, length as
      m-dash]CC6H4-4-CO2H}3) was used to synthesize a permanently porous Mn(ii)-based
      acetylenic phosphine coordination material, PCM-48. This triply-interpenetrated
      MOF contains 1-D microchannels that are decorated with electron-rich and
      adsorbate-accessible acetylenic moieties and phosphine lone pairs. PCM-48 has a
      moderate room-temperature C2H2 adsorption capacity (25.54 cm3 g-1) and displays
      high separation selectivities for C2H2 over CH4 (C2H2/CH4 = 23.3), CO2 (C2H2/CO2
      = 4.3), and N2 (C2H2/N2 = 76.9) at 296 K.

PMID- 30116817
TI  - Precise mono-Cu+ ion doping enhanced electrogenerated chemiluminescence from Cd
      In-S supertetrahedral chalcogenide nanoclusters for dopamine detection.
AB  - Herein, the ECL behaviors of precise mono-Cu+ ion doped Cd-In-S supertetrahedral
      chalcogenide nanoclusters (Cu@CdInS NCs) were investigated, and the effect of
      mono-Cu+ ions at the vacancy site of NCs on ECL emission performance was also
      elucidated. Precise mono-Cu+ ion doping not only induced new ECL emission at 596
      nm with enhanced efficiency as high as 21.72% relative to [Ru(bpy)3]2+, but also
      improved acid tolerance of the ECL performances of NCs. In addition, a simple,
      fast and label-free dopamine ECL sensor with excellent selectivity was achieved.

PMID- 30116819
TI  - Pyridine-based low-temperature synthesis of CoN, Ni3N and Cu3N nanoparticles.
AB  - CoN, Ni3N and Cu3N nanoparticles were obtained by pyridine-based synthesis using
      CoI2, NiI2, and CuI as the starting materials as well as NH3/KNH2 as the base and
      nitride source. Colloidally stable suspensions of crystalline, small-sized CoN
      (4.5 +/- 0.7 nm), Ni3N (2.7 +/- 0.4 nm), and Cu3N (4.2 +/- 0.7 nm) were
      instantaneously available from refluxing pyridine. This approach strictly avoids
      all oxygen sources (including starting materials and solvents), which is highly
      relevant with regard to the material purity and properties.

PMID- 30116818
TI  - Automated screening of C. elegans neurodegeneration mutants enabled by
      microfluidics and image analysis algorithms.
AB  - Spinal muscular atrophy (SMA) is a degenerative disorder that selectively
      deteriorates motor neurons due to a deficiency of survival motor neuron protein
      (SMN). The illness is the leading genetic cause of death in infants and is
      difficult to study in complex biological systems such as humans. A simpler model
      system, such as the nematode C. elegans, can be used to study potential
      mechanisms underlying this disease; C. elegans expresses the smn-1 gene, a
      homologue of SMN; powerful genetic tools in C. elegans research can be used to
      discover novel genes whose effect on SMN remains unknown or uncharacterized.
      Currently, conventional screening methods are time-consuming and laborious, as
      well as being subjective and mostly qualitative. To address these issues, we
      engineer an automated system capable of performing genetic suppressor screens on
      C. elegans using microfluidics in combination with custom image analysis
      software. We demonstrate the utility of this system by isolating 21 alleles that
      significantly suppress motor neuron degeneration at a screening rate of
      approximately 300 worms per hour. Many of these mutants also have improved motor
      function. These isolated alleles can potentially be further studied to understand
      mechanisms of protection against neurodegeneration. Our system is easily
      adaptable, providing a means to saturate screens not only implicated in the smn-1
      pathway, but also for genes involved in other neurodegenerative phenotypes.

PMID- 30116820
TI  - Effect of density on the thermal decomposition mechanism of epsilon-CL-20: a
      ReaxFF reactive molecular dynamics simulation study.
AB  - The explosive detonation reaction occurs when explosives are compressed by
      different shock strengths, and the degree of compression affects the chemical
      reaction of the detonation process. The thermal decomposition mechanism of
      explosives under different compression densities has thus attracted significant
      research interest, and a better understanding of this mechanism would be helpful
      for determining the mechanism of the detonation reaction of explosives. In this
      study, a epsilon-CL-20 supercell was constructed, and the thermal decomposition
      was calculated at different compression densities and temperatures using
      molecular dynamics simulations based on the ReaxFF-lg reactive force field. We
      analyzed the effect of density on the main elementary reaction, which consists of
      the initial reaction and the formation of final products. In addition, we studied
      the effect of density on the generation of clusters and the reaction kinetics of
      the thermal decomposition. The results indicate that the initial reaction pathway
      of the CL-20 molecule is the cleavage of the N-NO2 bond at different densities
      and that the frequency of N-NO2 bond breakage decreases at high density. As the
      density increases, clusters easily form and are resistant to decomposition at the
      later stage of thermal decomposition, which eventually leads to a decrease in the
      number of final products. Increasing the initial density of CL-20 significantly
      increases the reaction rate of the initial decomposition but hardly changes the
      activation energy of the decomposition.

PMID- 30116821
TI  - ESIPT-based ratiometric fluorescence probe for the intracellular imaging of
      peroxynitrite.
AB  - In this work, we set out to develop an endoplasmic reticulum (ER) directed ESIPT
      based ONOO- ratiometric fluorescent probe (ABAH-LW). ABAH-LW was synthesized in
      four steps and found to have a high sensitivity and selectivity towards the
      detection of ONOO-. ABAH-LW was able to detect low concentrations of ONOO- (limit
      of detection = 21.4 nM) within seconds producing a ratiometric change in
      fluorescence intensity. ABAH-LW further demonstrated the ability to
      ratiometrically image endogenous and exogenous ONOO- in HeLa cells. Moreover, co
      localization experiments were carried out using commercially available ER-Tracker
      Red, Lyso-Tracker Red and Mito-Tracker-Red, which were co-stained with ABAH-LW in
      HeLa cells. For ER-Tracker Red, Pearson's correlation co-efficient of 0.93 was
      determined and 3D surface plot analysis illustrated a large overlap between ABAH
      LW and ER-Tracker Red using both red and blue channels. In addition some co
      localisation with Mito-Tracker Red and ABAH-LW was observed (0.73).

PMID- 30116822
TI  - Metal coordination induced ring contraction of porphyrin derivatives.
AB  - A remarkable rearrangement of a diferrocenylporphyrin to give a silver(iii)
      corrole has been discovered. Compared to the previously reported porphyrin to
      corrole ring conversions (extremely rare and poor reaction yields), our
      methodology delivers near quantitative yield for this ring contraction.

PMID- 30116823
TI  - Synthesis of outer tube-selectively nitrogen-doped double-walled carbon nanotubes
      by nitrogen plasma treatment.
AB  - We demonstrate selective nitrogen doping on the outer tubes of double walled
      carbon nanotubes by nitrogen plasma treatment. Such selectivity improves the
      chemical activity of the outer tubes, including their wettability and oxygen
      reduction reaction properties, while retaining the structural, optical, and
      electrical properties of the inner tubes.

PMID- 30116824
TI  - Unravelling the enigma of ultrafast excited state relaxation in non-emissive
      aggregating conjugated polymers.
AB  - We investigate a class of non-emissive conjugated polymers with very short
      excited state lifetimes believed to undergo singlet fission and relaxation to mid
      gap forbidden excited states. Poly(3-decylthieneylenvinylene) (P3DTV) and its
      heavy atom analog, poly(3-decylseleneylenvinylene) (P3DSV), are strongly
      aggregating conjugated polymers that experience large excited state displacements
      along multiple vibrational modes. We demonstrate this Franck-Condon vibrational
      activity effectively disperses excitation energy into multiple non-radiative
      channels that can be explained using a simple, two-state potential energy surface
      model. Resonance Raman spectroscopy is sensitive to early Franck-Condon
      vibrational activity and we observe rich harmonic progressions involving multiple
      high frequency CC backbone symmetric stretching motions (~1000-1600 cm-1) in both
      systems reflecting mode-specific excited state geometrical displacements.
      Transient absorption spectra confirm that efficient non-radiative processes
      dominate excited state relaxation dynamics which are confined to pi-stacked
      aggregated chains. Surprisingly, we found little influence of the heteroatom
      consistent with efficient vibrational energy dissipation. Our results highlight
      the importance of aggregation and multi-dimensional Franck-Condon vibrational
      dynamics on the ability to harvest excitons, which are not usually considered in
      materials design and optimization schemes.

PMID- 30116825
TI  - Iodine-mediated cross-dehydrogenative coupling of pyrazolones and alkenes.
AB  - An iodine-mediated alkenylation of pyrazolones with simple alkenes under an air
      atmosphere has been developed. By this protocol, the pharmaceutically relevant
      pyrazolone scaffold was directly adorned with a readily transformable olefinic
      functional group through a cross-dehydrogenative coupling process in moderate to
      excellent yields. The coupling products could be facilely manipulated by, for
      example, the Heck reaction and hydrogenation treatment, thus enriching the
      pyrazolone derivatives. Based on the observation of the reaction intermediate and
      mechanistical experiments, two possible reaction pathways were proposed.

PMID- 30116826
TI  - Perspectives on the design of nanoparticle systems for catalysis.
AB  - An overview of the Faraday Discussion, "Designing Nanoparticle Systems for
      Catalysis", is presented. Examples are taken from the papers presented at the
      meeting and from the literature to illustrate the main discussion points.

PMID- 30116827
TI  - Stereotactic radiotherapy for choroidal melanomas by means of HybridArcTM :
      Physics and technique of linac-based photon beam therapy.
AB  - PURPOSE: Stereotactic radiotherapy (SRT) is suitable to treat ocular tumours. The
      optimal beam geometry for SRT, however, has not been defined. Here we evaluate a
      combination technique with dynamic conformal arcs (DCAs) and intensity-modulated
      static fields (IMRT), known as HybridArcTM (HA). METHODS: For the first
      consecutive 25 cases with choroidal melanomas with volumes of 0.02 to 1.18 cm3
      treated with 50 Gy in five fractions, the results with respect to dose
      conformity, homogeneity, and dose distributions were summarised. To describe the
      dose distribution at the planning target volume (PTV) boundary, we defined a
      spatially averaged dose gradient (SADG) and compared it with Paddick's gradient
      index (GI). We made dosimetric comparisons between HA and other irradiation
      techniques. RESULTS: The PTVs ranged from 0.42 to 3.37 cm3. The conformity index
      (CI) was 1.25 +/- 0.15, and the homogeneity index (HI) 0.08 +/- 0.02. The SADG
      was (-3.5 +/- 0.5) Gy/mm or (-7.0 +/- 1.0) %/mm between the isodose levels 95 and
      20%; local minima reached -11.5 Gy/mm or -22.9%/mm. The coefficient of
      determination for a nonlinear regression of GI on SADG was 0.072. After a median
      follow-up time of 19.6 months, local tumour control was 100% without any case of
      post-therapeutic enucleation. Two patients (8%) developed liver metastases.
      CONCLUSION: SRT of ocular tumours by HA is highly appropriate, and HA is superior
      to intensity-modulated arc therapy (IMAT) concerning dose reduction in organs at
      risk (OARs). The novel gradient measure SADG is more informative than Paddick's
      GI.

PMID- 30116829
TI  - Optimal sampling time and clinical implication of the SCN5A promoter haplotype in
      propafenone therapeutic drug monitoring.
AB  - PURPOSE: The clinical usefulness of therapeutic drug monitoring (TDM) of
      propafenone, a sodium channel blocker, has been unclear due to the lack of
      information regarding optimal blood sampling time and therapeutic concentration
      range. Antiarrhythmic effects of sodium channel blockers are affected by the
      activity of the cardiac sodium channel (SCN5A). We investigated the optimal
      sampling time and the clinical implication of the SCN5A promoter haplotype in
      propafenone TDM. METHODS: We evaluated serum concentrations of propafenone, the
      SCN5A promoter haplotype, and antiarrhythmic efficacy in 55 patients with
      supraventricular tachy-arrhythmias. Blood samples obtained 1.5-6 and 10-24 h
      after the last dose were categorized as peak and trough samples, respectively.
      RESULTS: The peak propafenone concentration was significantly higher in
      effectively treated patients than that in patients showing insufficient response
      (337 +/- 213 vs. 177 +/- 93 ng/mL, P = 0.005), but the trough propafenone
      concentration was not significantly different between the two groups (68 +/- 48
      vs. 42 +/- 36 ng/mL). Clinically relevant propafenone efficacy was achieved
      significantly more often in SCN5A haplotype B carriers than in wild-type
      haplotype A homozygotes (90 vs. 60%, P < 0.05). Among the haplotype A
      homozygotes, peak propafenone concentration was higher in effectively treated
      patients than that in patients showing insufficient response (299 +/- 177 vs. 177
      +/- 93 ng/mL, P = 0.061). CONCLUSION: The present study found that antiarrhythmic
      efficacy of propafenone was associated with peak propafenone concentration rather
      than trough concentration and was affected by the SCN5A promoter haplotype.

PMID- 30116828
TI  - Risk factors for stroke and choice of oral anticoagulant in atrial fibrillation.
AB  - PURPOSE: To investigate risk factors for stroke in patients initiating oral
      anticoagulants for atrial fibrillation in Norway and their association with
      receiving DOACs versus warfarin. METHODS: From nationwide registries, we
      identified naive users initiating treatment with warfarin, dabigatran,
      rivaroxaban, or apixaban for atrial fibrillation from 2010 to 2015 in Norway. We
      studied temporal changes in the CHA2DS2-VASc score and its component risk
      factors. We used multiple logistic regressions to identify CHA2DS2-VASc risk
      factors associated with receiving DOACs versus warfarin in 2015. RESULTS: From
      2010 to 2015, the yearly number of new oral anticoagulant users increased from
      7588 to 13,344. All new users initiated warfarin in 2010, while 86% initiated a
      DOAC in 2015. The mean CHA2DS2-VASc score decreased from 3.2 (SD 1.7) to 3.1 (SD
      1.6) in the same period. Vascular disease (0.56 [0.49-0.63]), congestive heart
      failure (OR 0.65 [95% CI 0.58-0.72]), and diabetes (0.83 [0.73-0.95]) decreased
      the odds of receiving DOACs instead of warfarin, and ischemic stroke/transient
      ischemic attack/arterial thromboembolism (1.31 [1.12-1.54]), age 65-74 (1.23
      [1.06-1.43]), and female sex (1.22 [1.10-1.36]) increased it. Age >= 75
      (reference age < 65) and hypertension had no impact. CONCLUSIONS: The uptake of
      DOACs was rapid and spurred an increase in new users of oral anticoagulants for
      atrial fibrillation from 2010 to 2015 in Norway. The mean CHA2DS2-VASc score did
      not change substantially during this period. Vascular disease, heart failure, and
      diabetes were associated with initiation of warfarin, and previous stroke, age 65
      74 and female sex with initiation of DOACs.

PMID- 30116830
TI  - Cortical Bone Loss in a Spontaneous Murine Model of Systemic Lupus Erythematosus.
AB  - Patients with systemic lupus erythematosus (SLE), a chronic inflammatory disease
      characterized by loss of T- and B-cell tolerance to autoantigens, are at
      increased risk for osteoporosis and fractures. Mice deficient in Fc gamma
      receptor IIb (FcgammaRIIB) exhibit spontaneous SLE and its restoration rescues
      the disease. To determine whether deleting FcgammaRIIB affects cortical bone mass
      and mechanical properties, we analyzed cortical bone phenotype of FcgammaRIIB
      knockouts at different ages. FACS analysis revealed that 6-month-old FcgammaRIIB
      /- mice had increased B220lowCD138+ cells, markers of plasma cells, indicating
      active SLE disease. In contrast, 3-month-old FcgammaRIIB-/- mice did not develop
      the active SLE disease. uCT analysis indicated that FcgammaRIIB deletion did not
      affect cortical bone in 3-month-old mutants. However, 6- and 10-month-old
      FcgammaRIIB-/- males and females had osteopenic cortical bone and the severity of
      bone loss increased with disease duration. FcgammaRIIB deletion decreased cross
      sectional area, cortical area, and marrow area in 6-month-old males. Cortical
      area and cortical thickness were decreased in 10-month-old FcgammaRIIB-/- males.
      Lack of FcgammaRIIB decreased cortical thickness without affecting cortical area
      in females. However, deletion of a single FcgammaRIIB allele was insufficient to
      induce cortical bone loss. The bending strength was decreased in 6- and 10-month
      old FcgammaRIIB-deficient males compared to WT controls. A microindentation
      analysis demonstrated significantly decreased hardness in both 10-month-old
      FcgammaRIIB-/- males and females. Our data indicate that FcgammaRIIB contributes
      to the regulation of cortical bone homeostasis subsequent to SLE development and
      that deletion of FcgammaRIIB in mice leads to SLE-like disease associated with
      cortical bone loss and decreased bending strength and hardness.

PMID- 30116831
TI  - [Improved quality of healthcare through dermatological health services research :
      Effects of structured programs on psoriasis and skin cancer].
AB  - There are diseases that are noticeable for the respective patients, but not
      visible for all others. And there are skin diseases which, due to their clearly
      visible location on the skin surface, are often easily recognisable to others.
      Nevertheless, in recent years dermatology has changed from a traditional optical
      subject, characterized by clinical observation, to a causal-oriented subject. At
      ever shorter intervals, new therapeutic options are emerging which present
      dermatology with a multitude of challenges. This raises questions not only about
      benefits and effectiveness, but also about financing, self-regulation and the
      holistic well-being of sick people. The decisive factor in all considerations for
      and against an innovation or change is the sovereignty over well-founded data on
      the actual supply situation. Both German dermatological associations, the
      Professional Association of German Dermatologists (Berufsverband der Deutschen
      Dermatologen, BVDD) and the German Dermatological Society (Deutsche
      Dermatologische Gesellschaft, DDG), recognized the need for coordinated
      scientific research in the field of dermatology healthcare with the establishment
      of the German Center for Health Services Research in Dermatology
      (Competenzzentrum Versorgungsforschung in der Dermatologie, CVderm) and had
      already in 2005 set the course for a long-term positioning of dermatological
      healthcare research.

PMID- 30116832
TI  - [Surgical urinary diversion in children from war and crisis areas-20-year
      experience report].
AB  - BACKGROUND: Because sick and injured children from war and crisis areas can often
      only be helped to a limited extent in their countries of origin, those children
      with the most complex diseases often receive medical treatment in Europe.
      MATERIALS AND METHODS: To evaluate the postoperative outcome of reconstructive
      interventions in children from war and crisis areas, an evaluation of the
      clinic's internal database between 1997 and 2017 was carried out. The operative
      indication, the surgical procedure, any revisions or conversions and the overall
      mortality were analyzed. RESULTS: During the above-mentioned period a total of 44
      (male: 32, female: 12) children aged 3-14 years from Afghanistan, Angola, Central
      Asia and the Caucasus were treated. Indications for the reconstructive procedures
      were bladder exstrophy (n = 23), neurogenic bladder dysfunction (n = 9), penile
      partial amputation (n = 1) and traumatic bladder dysfunction (n = 11). In 26
      children, a conduit was created, 11 children received a sigma rectum pouch and 1
      child an ileocecal pouch, while 5 other children received bladder augmentation
      and 1 child an oral mucosal urethroplasty. In total, 7 revisions or conversions
      due to ureteral implantation stenoses and recurrent acidosis had to be performed.
      Five children died in their home country due to acidosis, sepsis, end stage renal
      failure, accident and social exclusion. CONCLUSION: In the long term 39 of the 44
      (88.6%) children live socially integrated in their home country and are regularly
      monitored by local aid organizations. When choosing the reconstructive
      intervention, the local conditions must be considered.

PMID- 30116834
TI  - Pediatric radiology mission work: opportunities, challenges and outcomes.

PMID- 30116835
TI  - [Prolonged grief disorder].
AB  - Grief is a natural response to the loss of a loved one and its intensity usually
      lessens over time. Approximately 10% of bereaved persons, however, experience
      persistent symptoms resulting in the development of a prolonged grief disorder
      (PGD). A PGD shows a distinct symptom cluster and is considered for inclusion as
      a diagnosis in the upcoming revision of the International Statistical
      Classification of Diseases and Related Health Problems (ICD-11). It is distinct
      from other mental disorders but symptoms overlap, especially with major
      depression and posttraumatic stress disorder. In addition to diagnostic criteria
      and differential diagnosis, the following article also describes prevalence
      rates, comorbidities, risk factors as well as treatment options for PGD.

PMID- 30116836
TI  - Robust Domination of Lactobacillus sakei in Microbiota During Traditional
      Japanese Sake Starter Yamahai-Moto Fermentation and the Accompanying Changes in
      Metabolites.
AB  - The successful production of sake (Japanese rice wine) is brought about by
      drastic changes in microbial flora and chemical components during fermentation.
      In the traditional manufacturing process of sake starter (yamahai-moto),
      spontaneous growth of lactic acid bacteria suppresses inappropriate
      microorganisms and prepares the optimum environment for the alcohol fermentative
      yeast. In this study, we analyzed the changes in bacterial flora and chemical
      components of yamahai-moto. High-throughput next-generation sequencing (NGS) of
      the 16S ribosomal RNA gene V4 region revealed that various kinds of bacteria,
      including nitrate-reducing bacteria, existed in the early fermentation stage;
      however, Lactobacillus sakei then increased drastically to become dominant in the
      middle stage. Interestingly, this result was different from that obtained in the
      previous year at the same manufacturer; the early-stage major bacterium was
      Lactobacillus acidipiscis. Lactic acid, glucose, isomaltose, and total free amino
      acids increased throughout the fermentation process, which was attributable to
      the metabolism of L. sakei and the koji mold. It is noteworthy that significant
      ornithine accumulation and arginine consumption were observed from the middle to
      late stages. Thirty-eight percent of the L. sakei isolates from yamahai-moto
      exhibited significant ornithine production, indicating that the arginine
      deiminase pathway of L. sakei was working to survive the extremely low pH
      environment of the moto after the middle stage. This is the first report that
      includes concurrent analyses of the NGS-based bacterial flora and chemical
      components of yamahai-moto, providing further knowledge to help understand and
      improve the process of sake brewing.

PMID- 30116837
TI  - Propensity score analysis of 18-FDG PET/CT-enhanced staging in patients
      undergoing surgery for esophageal cancer.
AB  - PURPOSE: PET/CT is now integral to the staging pathway for potentially curable
      esophageal cancer (EC), primarily to identify distant metastases undetected by
      computed tomography. The aim of this study was to analyze the effect of PET/CT
      introduction on survival and assess patterns of recurrence after esophagectomy.
      METHODS: A longitudinal cohort of EC patients staged between 1998 and 2016 were
      considered for inclusion. After co-variate adjustment using propensity scoring, a
      cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent
      esophagectomy [median age 63 years (31-80), 395 males, 425 adenocarcinomas, 71
      squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary
      outcome measure was overall survival (OS) based on intention to treat. RESULTS:
      Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi2 6.571,
      df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28
      1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04-1.19], p = 0.001) and PET/CT
      staging (HR 0.688 [95% CI 0.53-0.89] p = 0.004) were independently associated
      with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT,
      compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to
      be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006).
      CONCLUSIONS: Enhanced PET/CT staging is an important modality and independent
      factor associated with improved survival in patients undergoing esophagectomy for
      cancer.

PMID- 30116839
TI  - Suitability of Wild Boar (Sus scrofa) as a Bioindicator for Environmental
      Pollution with Perfluorooctanoic Acid (PFOA) and Perfluorooctanesulfonic Acid
      (PFOS).
AB  - Wildlife species, such as roe deer, moose, brown hare, wild boar, etc., are known
      to accumulate persistent environmental contaminants and thus are useful as
      bioindicators for environmental pollution. Wild boars become exposed to
      perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) from flora,
      fauna, water, and soil. The main exposure pathway to PFOA and PFOS is assumed to
      be the oral intake. From studies in domestic pigs (belonging to the same species
      Sus scrofa), it has been established that the oral exposure results in the liver
      accumulation of PFOA and PFOS. Thus, we posit that wild boars can be
      quantitatively used as suitable bioindicators for the presence of these
      substances in the environment. After the environmental pollution case in the
      Hessian region Sauerland in 2006, monitoring programs of individual Federal
      States from 2007 to 2013 showed that almost all wild boar liver samples contained
      PFOA and PFOS. In 2014, the analyses of PFOA and PFOS in liver of wild boars
      hunted in the south, north, and west of Germany showed liver concentrations at
      the same level among regions. Overall, an average ratio of PFOS:PFOA
      concentration in liver of 20.5:1 was found. To estimate the actual ratio of
      PFOS:PFOA in the wild boars' dietary exposure, we performed toxicokinetic
      modeling. According to the model, the PFOS exposure is only 2.2 times that of
      PFOA (because PFOS has slower elimination kinetics and higher affinity for the
      liver than PFOA). Overall, the determination of PFOA and PFOS in liver of wild
      boars indicates that both substances are ubiquitously distributed in the
      environment. At the same time, higher exposures were found for animals living in
      closer proximity to dense human populations.

PMID- 30116838
TI  - A fluorescent material for the detection of chlortetracycline based on
      molecularly imprinted silica-graphitic carbon nitride composite.
AB  - A new fluorescent probe based on graphitic carbon nitride (g-C3N4) combined with
      molecularly imprinted silica was successfully fabricated and used to selectively
      recognize chlortetracycline (CTC). The g-C3N4 used in this study has the
      characteristics of low toxicity and high chemical stability. This synthetic
      composite was characterized by transmission electron microscopy, Fourier
      transform infrared spectroscopy, UV spectroscopy, X-ray diffraction, and
      fluorescence spectroscopy. The material was used to detect CTC by the
      fluorescence quenching technique. The fluorescence quenching was due to g-C3N4
      and the benzene ring of CTC through pi-pi electron donor-acceptor interaction and
      electrostatic force. Hydrogen bonds formed between CTC and 3
      aminopropyltriethoxysilane during the polymerization process. Eventually, a
      considerable amount of selective recognition holes were formed in the composite
      material and could specifically recognize the template molecule CTC. In addition,
      the probe strategy was successfully applied to milk analysis, and the recoveries
      ranged from 90.1% to 95.7%, with relative standard deviations of 1.8-2.8%; the
      detection limit for CTC was 8 ng mL-1. The results indicate that this method
      combined the sensitivity of fluorescence detection with the excellent selectivity
      of a molecularly imprinted polymer. The new material can be widely used in the
      detection of dairy products. Graphical abstract Schematic of synthesis of the MIP
      capped g-C3N4 by sol-gel reaction.

PMID- 30116840
TI  - A sectional anatomy learning tool for medical students: development and user
      usage analytics.
AB  - BACKGROUND: A sound knowledge of cross-sectional anatomy is needed to interpret
      radiological images. Ultrathin E12-plastinated slices serve as good learning
      resources to begin with, but effective utilisation of these resources are often
      challenging due to their fragility and lack of adequate laboratory time. To
      enhance interpretation of E12 slices, and also to promote independent learning,
      we developed a web-based self learning resource. METHODS: An interactive online
      sectional anatomy learning tool (SALT) to learn the cross-sectional anatomy of
      the spinal levels, thorax, abdomen and pelvis was developed using Courselab
      software. SALT was piloted on third-year medical students learning regional and
      clinical anatomy of the human body. At the end of the academic year, student
      participation within the resource was analysed, and the resource usage was
      compared with the users' academic performance. RESULTS: Each aspect of SALT was
      accessed 338 times on average, by 51% of the class. The majority medical students
      accessed the resource after class hours. Continued research usage was observed on
      weekends and holidays, which peaked during exam periods. SALT usage also had a
      positive impact on the users' academic performance (p < 0.05). Students also used
      the resource after exams and during their subsequent years of study. CONCLUSION:
      SALT promoted independent learning, as well as enhanced students' learning
      experience and academic performance. Having the benefit of online access, the
      resource was used almost 24/7, both on and off-campus. Educators should be
      encouraged to develop and trial their own simple inexpensive online resources
      tailormade to meet student needs and supplement to the existing traditional
      teaching techniques.

PMID- 30116842
TI  - beta-Diglycosidases from microorganisms as industrial biocatalysts: biochemical
      characteristics and potential applications.
AB  - Flavonoid glycoside degradation can proceed through two alternative enzymatic
      pathways: one that is mediated by monoglycosidases, and the other catalyzed by a
      diglycosidase. beta-Diglycosidase performs the flavonoid deglycosylation in a
      single reaction. The characterized beta-diglycosidase activities recognize the
      following disaccharidic sugar moieties: beta-primeverose, acuminose, vicianose,
      and beta-rutinose. The present paper reviews the biochemical characteristics and
      potential industrial applications of microbial beta-diglycosidases that break
      down plant diglycoconjugated flavonoids.

PMID- 30116843
TI  - Urinary symptoms are associated with certain urinary microbes in urogynecologic
      surgical patients.
AB  - INTRODUCTION AND HYPOTHESIS: Persistent and de novo symptoms decrease
      satisfaction after urogynecologic surgery. We investigated whether the
      preoperative bladder microbiome is associated with urinary symptoms prior to and
      after urogynecologic surgery. METHODS: One hundred twenty-six participants
      contributed responses to the validated OABq symptom questionnaire. Catheterized
      (bladder) urine samples and vaginal and perineal swabs were collected immediately
      preoperatively. Bacterial DNA in the urine samples and swabs was sequenced and
      classified. RESULTS: Preoperative symptom severity was significantly worse in
      sequence-positive patients. Higher OABq Symptom Severity (OABqSS) scores (more
      symptomatic) were associated with higher abundance in bladder urine of two
      bacterial species: Atopobium vaginae and Finegoldia magna. The presence of
      Atopobium vaginae in bladder urine also was correlated with its presence in
      either the vagina or perineum. CONCLUSIONS: Two specific bacterial species
      detected in bladder urine, Atopobium vaginae and Finegoldia magna, are associated
      with preoperative urinary symptom severity in women undergoing POP/SUI surgery.
      The reservoir for Atopobium vaginae may be adjacent pelvic floor niches. This
      observation should be validated in a larger cohort to determine whether there is
      a microbiologic etiology for certain preoperative urinary symptoms.

PMID- 30116841
TI  - White matter microstructural abnormalities in blast-exposed combat veterans:
      accounting for potential pre-injury factors using consanguineous controls.
AB  - PURPOSE: Assess the prevalence of white matter microstructural changes in combat
      veterans, within the context of a highly matched control group comprising
      unexposed close relatives. METHODS: This prospective study had institutional
      review board approval, included written informed consent, and is HIPAA-compliant.
      Diffusion tensor imaging was analyzed in 16 male blast-exposed combat veterans of
      Operation Iraqi Freedom/Operation Enduring Freedom (mean age 31.0 years) and 18
      unexposed males (mean age 30.4 years) chosen on the basis of a consanguineous
      relationship to a member of the subject group. Whole-brain voxel-based comparison
      of fractional anisotropy (FA) was performed using both group and individual
      analyses. Areas where effects on FA were detected were subsequently characterized
      by extracting radial diffusivity (RD), axial diffusivity (AD), and mean
      diffusivity (MD) from the regions of abnormal FA. RESULTS: Controls did not
      differ from veterans on any background demographic factor. In voxel-based group
      comparison, we identify high fractional anisotropy (FA) in veterans compared to
      controls (p < 0.01). Within individual veterans, we find multiple areas of both
      abnormally high and low FA (p < 0.01) in a heterogeneous distribution, consistent
      with multifocal traumatic axonal injury. In individualized analyses, low FA areas
      demonstrate high radial diffusivity, whereas high FA areas demonstrate low RD in
      both group and individual analyses. CONCLUSIONS: Combat-related blast exposure is
      associated with microstructural white matter abnormalities, and the nature of the
      control group decreases the likelihood that the findings reflect underlying
      background differences. Abnormalities are heterogeneously distributed across
      patients, consistent with TAI, and include areas of low and high FA.

PMID- 30116844
TI  - "Occult" pelvic abscess following previous robotic sacrocolpopexy.

PMID- 30116845
TI  - Do anxiety traits predict subjective short-term outcomes following prolapse
      repair surgery?
AB  - BACKGROUND: Studies conducted in orthopedic surgery have suggested that patients
      with anxiety have less symptomatic improvement following surgery than those
      without. We hypothesized for this study that patients with anxiety traits
      experience less symptomatic improvement following pelvic organ prolapse surgery
      than patients without. METHODS: All patients presenting for prolapse repair
      surgery were offered enrollment in this prospective cohort study. Prior to
      surgery, subjects were asked to complete the Spielberger State-Trait Anxiety
      Inventory and the Pelvic Floor Distress Inventory 20. Subjects were also asked to
      list up to five goals related to the outcome of surgery for goal-attainment
      scaling. At the 6-8-week postoperative visit, subjects were asked to repeat the
      STAI and PFDI questionnaires and respond to the single question tool assessing
      Patient Global Impression of Improvement. Subjects were also asked to rate on a
      Visual Assessment Scale how well preoperative goals were met. All three
      questionnaires were repeated at >12 weeks following surgery. RESULTS: A total of
      32 patients with anxiety trait and 58 without were recruited. Preoperatively, the
      mean STAI-T was 45.0 (+/- 7.2.) and 27.7 (+/- 4.9) for subjects with and without
      anxiety; PFDI 20 scores were 96.1 (+/- 48.8) and 94.7 (+/- 57.5), respectively.
      At 12+ weeks postoperatively, the mean PFDI-20 for subjects with anxiety was 31.3
      (+/- 20.9) and 30.3 (+/- 27.9) (p = 0.22) for those without. CONCLUSIONS: We did
      not find the anxiety trait to be a predictor of subjective outcomes following
      pelvic organ prolapse surgery.

PMID- 30116846
TI  - [Tumors of the paranasal sinus invading the orbit].
AB  - Invasion of the orbit by tumors of the paranasal sinus represents an advanced
      state of disease. Prognosis has hardly improved in recent decades, despite
      multimodal therapeutic approaches. Complete resection of the tumor still remains
      the most promising therapy. Orbital exenteration implies a dramatic event for the
      patient's psyche and quality of life. If the eye that would have to be
      exenterated is the only one remaining with sufficient vision, exenteration should
      be abandoned in consensus with the patient. Aesthetic improvements following
      exenteration can be achieved by surgical and prosthetic techniques. The method of
      prosthesis fixation needs to be determined with respect to the patients'
      individual expectations and manual abilities. The main aspects of functional
      rehabilitation are good local cleanability and sufficient nasal breathing without
      encrusted mucus, which can be achieved by restoring the natural laminar airflow.
      Tumors of the paranasal sinus with orbital invasion represent a diagnostic and
      therapeutic challenge. The information regarding prognosis, therapeutic
      approaches, post-therapeutic quality of life, and rehabilitation options should
      be thoroughly discussed by patients and therapists prior to treatment.

PMID- 30116847
TI  - Liposomal therapies in oncology: does one size fit all?
AB  - Liposomal therapies opened the chapter of nanomedicine, in 1995, with the
      approval of liposomal doxorubicin (Doxil(r)) for the treatment of numerous types
      of cancer. For the first time, liposomes permitted the employment of potent
      chemotherapeutic agents with improved pharmacokinetic and pharmacodynamic
      profiles, with less undesired side effects. Liposomal therapies allow the drug
      encapsulation and more selective delivery in the tumor bed, particularly due to
      the enhanced permeation and retention effect. These unique characteristics
      explain why liposomal therapies are being increasingly considered as alternatives
      in cancer therapy and represent an important research field with the recent
      approval for clinical use and emergent formulations in clinical trials. Even so,
      the response rate of liposomal therapies varies between 5 and 71%, and they are
      still indistinguishably given to every patient. As already well-demonstrated for
      conventional chemotherapies and targeted therapies, there is also the need for
      predictive biomarkers that allow a better use of liposomal drugs, with higher
      patient quality of life. Our aim in this review was to address the approved
      liposomal therapies and to summarize the information concerning possible
      predictive markers of response in their various clinical applications, to
      personalize each patient treatment and maximize its efficacy.

PMID- 30116848
TI  - Rhodanobacter ginsengiterrae sp. nov., an antagonistic bacterium against root rot
      fungal pathogen Fusarium solani, isolated from ginseng rhizospheric soil.
AB  - A novel bacterium, designated DCY112T, was isolated from the rhizospheric soil of
      a ginseng-cultivated field in Gochang-gun, Republic of Korea. Based on 16S rRNA
      gene sequence analysis, this isolate was assigned to the genus Rhodanobacter and
      is closely related to Rhodanobacter soli DCY45T (98.0%) and R. umsongensis GR24
      2T (98.0%). Strain DCY112T is Gram-negative, catalase- and oxidase-positive,
      aerobic, non-motile, rod-shaped, and produces yellow-pigmented colonies on R2A
      medium. Q-8 was the predominant respiratory quinone. The major cellular fatty
      acids were iso-C15:0, iso-C17:0, and summed feature 9 (iso-C17:1 omega9c and/or
      10-methyl-C16:0). The major polar lipids were phosphatidylglycerol (PG),
      phosphatidylethanolamine (PE), an unknown amino lipid (AL1), and an unidentified
      polar lipid (L3). The genomic DNA G + C content was 65.2 mol%. DNA-DNA homology
      values between strain DCY112T and related strains were lower than 55%. The low
      DNA relatedness data in combination with phenotypic and genotypic tests indicated
      that strain DCY112T could not be assigned to a recognized species. Strain DCY112T
      showed antagonistic activity against the fungal pathogen Fusarium solani (KACC
      44891T), which causes ginseng root rot. The results of this study support that
      strain DCY112T is a novel species belonging to the genus Rhodanobacter, for which
      the name Rhodanobacter ginsengiterrae is proposed. The type strain is DCY112T (=
      KCTC 62018T = JCM 32167T).

PMID- 30116849
TI  - Heavy Metal Concentration in Largehead Hairtail (Trichiurus lepturus Linneaus,
      1758) and Savalai Hairtail (Lepturacanthus savala (Cuvier, 1829)) Obtained from
      Karachi Fish Harbour, Pakistan.
AB  - In this study, muscle samples gathered from Largehead hairtail (Trichiurus
      lepturus Linneaus, 1758) and Savali hairtail [Lepturacanthus savala (Cuvier,
      1829)] from the Karachi Fish Harbour, Pakistan were analyzed to determine heavy
      metal concentrations (iron [Fe], zinc [Zn], copper [Cu], manganese [Mn], lead
      [Pb] and cadmium [Cd]) between January and December 2016. All samples were
      analyzed using the AAnalyst 700 Flame Atomic Absorption Spectrophotometer. It was
      observed that the average measured level of Fe, Zn, Cu, Mn, Pb and Cd in muscle
      were 77.72 +/- 47.84 ug/g, 20.34 +/- 8.49 ug/g, 2.23 +/- 1.16 ug/g, 0.57 +/- 0.36
      ug/g, 0.20 +/- 0.16 ug/g and 0.42 +/- 0.19 ug/g for T. lepturus, respectively.
      Besides, the average level of the same metal concentrations in muscle for L.
      savala were 85.11 +/- 57.64 ug/g, 16.63 +/- 9.25 ug/g, 2.53 +/- 1.90 ug/g, 0.47
      +/- 0.27 ug/g, 0.23 +/- 0.18 ug/g and 0.47 +/- 0.20 ug/g, respectively. The
      correlation between size groups and metal accumulation in muscle tissues were
      investigated for both fish. In terms of public risk assessment, the provisional
      tolerable weekly intake's of various heavy metals were compared with the
      consumption of both fish. As a result of the analysis, Fe, Zn, Cu, Mn, Pb and Cd
      accumulations in muscle tissues of T. lepturus and L. savala collected from
      Karachi Fish Harbour Pakistan did not exceed limit values.

PMID- 30116850
TI  - Assessment of Cadmium Scavenging Potential of Canna indica L.
AB  - The aquatic plant, Canna indica L. (Indian shoot) of Cannaceae family was
      investigated to assess cadmium scavenging potential at 5, 10, 25, 50, 100 and 150
      mg Cd L-1 exposers. The results showed that Canna has considerable potential of
      cadmium accumulation, which was up to 58.69 and 10.13 mg Cd kg-1 dry weight in
      root and shoot of Canna, respectively. The effects of different cadmium levels on
      biomass production of plant tissues were significantly (p = 0.05) showed negative
      relation due to cadmium toxicity. The root concentration factor was higher than
      the bioconcentration factor which indicated the lower translocation factor of
      Canna. Considering the high root concentration factor, average bioconcentration
      factor, rapid growth and optimum adaptive properties up to 100 mg Cd L-1 level,
      the Canna could be employed as an eco-friendly and efficient aquatic plant for
      cadmium scavenging. This study plays a potential role in remediation of cadmium
      contaminated wastewater.

PMID- 30116851
TI  - Drugs of abuse from a different toxicological perspective: an updated review of
      cocaine genotoxicity.
AB  - Cocaine is one of the most widely consumed psychoactive substances and has been
      recognized as a major public health concern for many years. While several aspects
      of the toxicology of cocaine have been thoroughly described in the literature,
      namely its effects on different target organs, other toxicological features
      should not be disregarded. In this perspective, the in vitro and in vivo
      genotoxic effects of cocaine, along with the genotoxicity data from human
      exposure, especially in the context of "crack" smoking, were reviewed. Some
      concerns regarding (1) the chronic abuse and forms of cocaine, (2) the role of
      metabolism and (3) the mode of action of cocaine were discussed. The major
      limitations of the experimental and human studies available were also addressed
      and some research gaps in this field identified. Overall, although the
      genotoxicity of cocaine is still a matter of discussion, this psychoactive
      substance exhibits a genotoxic potential that should be further considered.

PMID- 30116852
TI  - [Update of the German S3 guideline on atraumatic femoral head necrosis in
      adults].
AB  - The update of the German S3 guideline on atraumatic femoral head necrosis in
      adults aims to provide an overview of diagnosis and treatment. All clinical
      studies, systematic reviews, and meta-analyses published in German or English
      between 01.05.2013 and 30.04.2017 were included. Of 427 studies, 28 were suitable
      for analysis. Risk factors are corticosteroids, chemotherapy, kidney transplants,
      hemoglobinopathies, and alcoholism. Differential diagnoses are for example bone
      marrow edema, insufficiency fracture, and destructive arthropathy. Radiography
      should be performed upon clinical suspicion. In patients with normal radiography
      findings but persistent complaints, magnetic resonance imaging (ARCO
      classification) is the method of choice. Computed tomography (CT) can be used to
      confirm/exclude articular surface collapse. A subchondral sclerosis zone >30% in
      CT indicates a better prognosis. Left untreated, a subchondral fracture will
      develop within 2 years. The risk of disease development in the opposite side is
      high during the first 2 years, but unlikely thereafter. In conservative therapy,
      iloprost and alendronate can be used in a curative approach, the latter for
      small, primarily medial necrosis. Conservative therapy alone as well as other
      drug-based and physical approaches are not suitable for treatment. No particular
      joint-preserving surgery can currently be recommended. Core decompression should
      be performed in early stages with <30% necrosis. From ARCO stage IIIc or in stage
      IV, the indication for total hip arthroplasty should be checked. Results after
      total hip arthroplasty are comparable with those after coxarthrosis, although the
      revision rate is higher due to the relatively young age of patients. Statements
      on the effectiveness of cell-based therapies such as expanded stem cells or bone
      marrow aspirates cannot currently be made.

PMID- 30116853
TI  - Impact of DNA repair and stability defects on cortical development.
AB  - Maintenance of genome stability is a crucial cellular function for normal
      mammalian development and physiology. However, despite the general relevance of
      this process, genome stability alteration due to genetic or non-genetic
      conditions has a particularly profound impact on the developing cerebral cortex.
      In this review, we will analyze the main pathways involved in maintenance of
      genome stability, the consequences of their alterations with regard to central
      nervous system development, as well as the possible molecular and cellular basis
      of this specificity.

PMID- 30116854
TI  - [Aspects of pulmonary involvement in inflammatory bowel disease].
AB  - The incidence of pulmonary manifestations of inflammatory bowel disease (IBD)
      appears to be much higher than previously assumed. In prospective studies,
      subclinical pulmonary interstitial infiltrates or pathological lung function were
      found in 40%-60% of IBD patients, both in children and adults. Pulmonary
      disorders can affect any part of the respiratory system, the most frequent
      pattern being inflammation of the large airways often associated with
      bronchiectasis. The differential diagnosis should include drug-related pulmonary
      disease and infectious causes when receiving immunosuppressive therapy. The
      diagnostic approach consists of a thorough history and clinical status as well as
      lung function tests including body plethysmography and high-resolution computed
      tomography of the thorax. Bronchoscopy with broncheoalveolar lavage and sample
      collection for histology as well as exclusion of pulmonary embolism may be
      indicated. Pulmonary disease in association with IBD can develop at any time
      during the course of IBD: in rare cases, symptoms can evolve even before
      gastrointestinal symptoms appear. On the other hand, there are frequent reports
      on the occurrence of pulmonary inflammation after proctocolectomy in patients
      with ulcerative colitis. The pathophysiologic background is largely unknown, but
      there seems to be an interaction between gastrointestinal and pulmonary
      inflammation. The mainstay of therapy are inhaled or systemic corticosteroids.
      Most patterns of pulmonary involvement in IBD respond well to corticosteroid
      therapy. Rarely, serious and persisting complications occur, such as strictures
      or stenosis of the large airways.

PMID- 30116855
TI  - [Pain medications for acute and chronic low back pain].
AB  - Low back pain is common. In the acute (duration <6 weeks) and subacute pain
      phases (6-12 weeks) the main goal of pharmacological pain treatment is to enable
      patients to move and to stay as active as possible. In the chronic phase, pain
      medications can support non-pharmacological measures and improve physical
      function. Although almost every person will experience low back pain at least
      once in a lifetime, for many pain medications no clinical studies on their
      efficacy exist. Most data are available on the efficacy of non-steroidal anti
      inflammatory drugs (NSAIDs) in acute and chronic low back pain; however,
      potential adverse effects and contraindications for NSAIDs need to be taken into
      account when the medication is prescribed. For other non-opioid medications (e.
      g. paracetamol, metamizole) the efficacy is not well studied. Weak and strong
      opioids have been shown to be effective compared to placebo in the short term;
      however, there is increasing evidence that opioids are no more effective than non
      opioid medications in the treatment of acute and chronic low back pain.
      Furthermore, gastrointestinal and central nervous system adverse effects of
      opioids should be considered. Conclusion: in low back pain, the choice of a
      specific pain medications is based on the individual patient preferences,
      contraindications, and potential adverse effects. The main goal of pain
      medications is to enable patients to stay active. In persisting pain, non
      pharmacological measures are important and should complement pharmacological pain
      treatment.

PMID- 30116856
TI  - A New Modeling Approach To Prioritize Riparian Restoration To Reduce Sediment
      Loading in Two Virginia River Basins.
AB  - Human impact, particularly land cover changes (e.g., agriculture, construction)
      increase erosion and sediment loading into streams. Benthic species are
      negatively affected by silt deposition that coats and embeds stream substrate.
      Given that riparian buffers are effective sediment filters, riparian restoration
      is increasingly implemented by conservation groups to protect stream habitats.
      Limited funding and a multitude of impaired streams warrant the need for cost
      effective prioritization of potential restoration actions. We created a decision
      support framework for conservation agencies and aquatic resource managers to
      prioritize riparian restoration efforts. Our framework integrates GIS data and
      field surveys into a statistical model to predict instream silt from estimates of
      upland soil loss and riparian filtration capacity. We focus specifically on
      prioritizing sites in upper sections of the Roanoke and Nottoway river basins
      (Virginia, US) based on observed records of Roanoke logperch (Percina rex), an
      imperiled sediment-sensitive species. Our statistical approach examines soil
      characteristics, land cover, precipitation, topography, and annual soil loss
      estimates from the empirically derived Revised Universal Soil Loss Equation,
      combined with land cover-based riparian filtration capacity as potential stream
      habitat predictors. We found riparian filtration capacity to be a significant
      predictor of silt cover, while precipitation was a significant predictor of
      embeddedness. Spatial scale was also a factor, in that spatial variance in silt
      cover and embeddedness was more accurately predicted at smaller spatial extents.
      Ultimately, our model can be used as a prioritization tool for mitigating high
      siltation areas, or for protecting low soil erosion areas.

PMID- 30116857
TI  - Obituary: Nico van Nuland 1961-2017.
AB  - This tribute to the life and work of Nico van Nuland highlights his
      interdisciplinary application of biophysical methods, especially high-resolution
      NMR spectroscopy and molecular dynamics simulations, to improve significantly our
      understanding of the structure, stability, dynamics and folding of proteins, and
      particularly of protein-protein interactions. His work as a colleague, team
      leader and collaborator highlights the importance of building scientific
      communities and of maintaining them, and of educating new generations of
      scientists.

PMID- 30116858
TI  - A precision medicine approach to pharmacological adjuncts to extinction: a call
      to broaden research.
AB  - There is a pressing need to improve treatments for anxiety. Although exposure
      based therapy is currently the gold-standard treatment, many people either do not
      respond to this therapy or experience a relapse of symptoms after treatment has
      ceased. In recent years, there have been many novel pharmacological agents
      identified in preclinical research that have potential as adjuncts for exposure
      therapy, yet very few of these are regularly integrated into clinical practice.
      Unfortunately, the robust effects observed in the laboratory animal often do not
      translate to a clinical population. In this review, we discuss how age, sex,
      genetics, stress, medications, diet, alcohol, and the microbiome can vary across
      a clinical population and yet are rarely considered in drug development. While
      not an exhaustive list, we have focused on these factors because they have been
      shown to influence an individual's vulnerability to anxiety and alter the
      neurotransmitter systems often targeted by pharmacological adjuncts to therapy.
      We argue that for potential adjuncts to be successfully translated from the lab
      to the clinic empirical research must be broadened to consider how individual
      difference factors will influence drug efficacy.

PMID- 30116860
TI  - A cFos activation map of remote fear memory attenuation.
AB  - RATIONALE: The experience of strong traumata leads to the formation of enduring
      fear memories that may degenerate into post-traumatic stress disorder. One of the
      most successful treatments for this condition consists of extinction training
      during which the repeated exposure to trauma-inducing stimuli in a safe
      environment results in an attenuation of the fearful component of trauma-related
      memories. While numerous studies have investigated the neural substrates of
      recent (e.g., 1-day-old) fear memory attenuation, much less is known about the
      neural networks mediating the attenuation of remote (e.g., 30-day-old) fear
      memories. Since extinction training becomes less effective when applied long
      after the original encoding of the traumatic memory, this represents an important
      gap in memory research. OBJECTIVES: Here, we aimed to generate a comprehensive
      map of brain activation upon effective remote fear memory attenuation in the
      mouse. METHODS: We developed an efficient extinction training paradigm for 1
      month-old contextual fear memory attenuation and performed cFos
      immunohistochemistry and network connectivity analyses on a set of cortical,
      amygdalar, thalamic, and hippocampal regions. RESULTS: Remote fear memory
      attenuation induced cFos in the prelimbic cortex, the basolateral amygdala, the
      nucleus reuniens of the thalamus, and the ventral fields of the hippocampal CA1
      and CA3. All these structures were equally recruited by remote fear memory
      recall, but not by the recall of a familiar neutral context. CONCLUSION: These
      results suggest that progressive fear attenuation mediated by repetitive exposure
      is accompanied by sustained neuronal activation and not reverted to a pre
      conditioning brain state. These findings contribute to the identification of
      brain areas as targets for therapeutic approaches against traumatic memories.

PMID- 30116861
TI  - Assessment of Avoidable Readmissions in a Visceral Surgery Department with an
      Algorithm: Methodology, Analysis and Measures for Improvement.
AB  - BACKGROUND: Standardized quality indicators assessing avoidable readmission
      become increasingly important in health care. They can identify improvements area
      and contribute to enhance the care delivered. However, the way of using them in
      practice was rarely described. METHODS: Retrospective study uses prospective
      inpatients' information. Thirty-day readmissions were deemed potentially
      avoidable or non-avoidable by a computerized algorithm, and annual rate was
      reported between 2010 and 2014. Observed rate was compared to expected rate, and
      medical record review of potentially avoidable readmissions was conducted on data
      between January and June 2014. RESULTS: During a period of ten semesters, 11,011
      stays were screened by the algorithm and a potentially avoidable readmission rate
      (PAR) of 7% was measured. Despite stable expected rate of 5 +/- 0.5%, an increase
      was noted concerning the observed rate since 2012, with a highest value of 9.4%
      during the first semester 2014. Medical chart review assessed the 109 patients
      screened positive for PAR during this period and measured a real rate of 7.8%.
      The delta was in part due to an underestimated case mix owing to sub-coded
      comorbidities and not to health care issue. CONCLUSIONS: The present study
      suggests a methodology for practical use of data, allowing a validated quality of
      care indicator. The trend of the observed PAR rate showed a clear increase, while
      the expected PAR rate was stable. The analysis emphasized the importance of
      adequate "coding chain" when such an algorithm is applied. Moreover, additional
      medical chart review is needed when results deviate from the norm.

PMID- 30116859
TI  - Plasma metabolomic profiling of a ketamine and placebo crossover trial of major
      depressive disorder and healthy control subjects.
AB  - (R,S)-Ketamine produces rapid, robust, and sustained antidepressant effects in
      major depressive disorder. Specifically, its pharmacological efficacy in
      treatment refractory depression is considered a major breakthrough in the field.
      However, the mechanism of action of ketamine's rapid effect remains to be
      determined. In order to identify pathways that are responsible for ketamine's
      effect, a targeted metabolomic approach was carried out using a double-blind,
      placebo-controlled crossover design, with infusion order randomized with
      medication-free patients with treatment-resistant major depressive disorder (29
      subjects) and healthy controls (25 subjects). The metabolomic profile of these
      subjects was characterized at multiple time points, and a comprehensive analysis
      was investigated between the following: MDD and healthy controls, treatment and
      placebo in both groups and the corresponding response to ketamine treatment.
      Ketamine treatment resulted in a general increase in circulating sphingomyelins,
      levels which were not correlated with response. Ketamine response resulted in
      more pronounced effects in the kynurenine pathway and the arginine pathway at 4 h
      post-infusion, where a larger decrease in circulating kynurenine levels and a
      larger increase in the bioavailability of arginine were observed in responders to
      ketamine treatment, suggesting possible mechanisms for response to ketamine
      treatment.

PMID- 30116862
TI  - The Reporting on ERAS Compliance, Outcomes, and Elements Research (RECOvER)
      Checklist: A Joint Statement by the ERAS(r) and ERAS(r) USA Societies.
AB  - BACKGROUND: Enhanced recovery after surgery (ERAS) programs are multimodal care
      pathways designed to minimize the physiological and psychological impact of
      surgery for patients. Increased compliance with ERAS guidelines is associated
      with improved patient outcomes across surgical types. As ERAS programs have
      proliferated, an unintentional effect has been significant variation in how ERAS
      related studies are reported in the literature. METHODS: To improve the quality
      of ERAS reporting, ERAS(r) USA and the ERAS(r) Society launched an effort to
      create an instrument to assist authors in manuscript preparation. Criteria to
      include were selected by a combination of literature review and expert opinion.
      The final checklist was refined by group consensus. RESULTS: The Societies
      present the Reporting on ERAS Compliance, Outcomes, and Elements Research
      (RECOvER) Checklist. The tool contains 20 items including best practices for
      reporting clinical pathways, compliance auditing, and formatting guidelines.
      CONCLUSIONS: The RECOvER Checklist is intended to provide a standardized
      framework for the reporting of ERAS-related studies. The checklist can also
      assist reviewers in evaluating the quality of ERAS-related manuscripts. Authors
      are encouraged to include the RECOvER Checklist when submitting ERAS-related
      studies to peer-reviewed journals.

PMID- 30116863
TI  - No evidence for cerebellar abnormality in adults with developmental dyslexia.
AB  - Developmental dyslexia is commonly believed to result from a deficiency in the
      recognition and processing of speech sounds. According to the cerebellar deficit
      hypothesis, this phonological deficit is caused by deficient cerebellar function.
      In the current study, 26 adults with developmental dyslexia and 25 non-dyslexic
      participants underwent testing of reading-related skills, cerebellar functions,
      and MRI scanning of the brain. Anatomical assessment of the cerebellum was
      conducted with voxel-based morphometry. Behavioural evidence, that was indicative
      of impaired cerebellar function, was found to co-occur with reading impairments
      in the dyslexic subjects, but a causal relation between the two was not observed.
      No differences in local grey matter volume, nor in structure-function
      relationships within the cerebellum were found between the two groups. Possibly,
      the observed behavioural pattern is due to aberrant white matter connectivity. In
      conclusion, no support for the cerebellar deficit hypothesis or the presence of
      anatomical differences of the cerebellum in adults with developmental dyslexia
      was found.

PMID- 30116864
TI  - Pre-stimulus theta power is correlated with variation of motor evoked potential
      latency: a single-pulse TMS study.
AB  - There has been a growing interest in the role of pre-stimulus oscillations on
      cortical excitability in visual and motor systems. Prior studies focused on the
      relationship between pre-stimulus neuronal activity and TMS-evoked motor evoked
      potentials (MEPs) have reported heterogeneous results. We aimed to assess the
      role of pre-stimulus neural activity on the latency of MEPs, which might enhance
      our understanding of the variability of MEP signals, and potentially provide
      information on the role played by cortical activity fluctuations in the
      excitability of corticospinal pathways. Near-threshold single-pulse TMS (spTMS)
      was applied at random intervals over the primary motor cortex of 14 healthy
      participants while they sat passively, to trigger hand muscle contractions.
      Multichannel EEG was recorded during spTMS blocks. Spearman correlations between
      both the variation in MEP onset latencies and peak-to-peak MEP amplitudes, and
      the pre-stimulus power of EEG oscillations were calculated across participants.
      We found that the variation in MEP latency was positively correlated with pre
      stimulus power in the theta range (4-7 Hz) in a broad time window (- 3.1 to - 1.9
      s) preceding the spTMS generating the MEP. No correlation between pre-stimulus
      power in any frequency band and MEP amplitude was found. Our results show that
      pre-stimulus theta oscillations are correlated with the variation in MEP latency,
      an outcome measure determined by fiber conduction velocity and synaptic delays
      along the corticospinal tract. This finding could prove useful for clinicians
      using MEP latency-based information in pre- or intra-operative diagnostics of
      corticospinal impairment.

PMID- 30116866
TI  - Clinical study of anterior hip ultrasound (van Douveren's method)-assisted Pavlik
      harness.
AB  - PURPOSE: To investigate the use of anterior hip ultrasound (van Douveren's
      method)-assisted Pavlik harness in developmental dysplasia of the hip (DDH).
      METHODS: Weekly anterior hip ultrasound scanning was performed in children with
      fixed Pavlik harness to detect whether hip reduction was achieved with the help
      of harness (the superior ramus of the pubis, the acetabulum, the femoral head,
      and the femoral neck being depicted in one plane indicated concentric reduction
      of the hip), and the stability of the reduction was checked by ultrasonography.
      RESULTS: A total of 39 child patients and 51 dysplastic hips were successfully
      detected by anterior ultrasound, and stable reduction was achieved in 37 hips (15
      Graf type D and 22 type III) right after the help of Pavlik harness, in seven
      hips (6 type III and 1 type IV) two weeks after the help of Pavlik harness; the
      remaining seven hips (2 type III and 5 type IV) failed to reach stable reduction
      after two weeks. CONCLUSION: The anterior hip ultrasound (van Douveren's method)
      can be used to detect the reduction and stability of hip after Pavlik harness
      treatment in children with DDH. The majority of Graf type D and III hips can
      achieve a stable concentric reduction right after the help of Pavlik harness,
      while severely dislocated type IV hips have a low success rate for harness
      treatment, and abandonment of harness therapy should be considered in early
      stage.

PMID- 30116865
TI  - Role of astrocytic MeCP2 in regulation of CNS myelination by affecting
      oligodendrocyte and neuronal physiology and axo-glial interactions.
AB  - Astrocytes perform several critical functions such as promoting neuronal
      maturation, neuronal survival, maintaining and supporting neurons and
      oligodendrocytes. Astrocytes participate in the formation of nodes of Ranvier.
      Recently, studies emphasizing on the role of astrocytes in regulating myelination
      by secreting pro-myelinating factors like growth factors, neurotrophins and ECM
      proteins, have been investigated by many researchers. Methyl-CpG-Binding Protein
      2 (MeCP2), an epigenetic protein, binds to CpG islands in the genome and induces
      multiple gene regulatory functions by conforming changes in the chromatin
      structure and resulting in cell-specific gene expression. MeCP2 deficient
      astrocytes have been linked with abnormal neuronal function including decreased
      dendritic arborization and decreased dendritic outgrowth. However, role of
      astrocytic MeCP2 in central nervous system myelination is largely not known. The
      data from the current study indicate altered mRNA levels (Lif, Cntf, Pdgfa,
      Cxcl10) of astrocyte-secreted factors involved in myelination. Bdnf and Ngf mRNA
      levels were also altered in MeCP2 knockdown astrocytes. Moreover, the secreted
      BDNF levels were significantly altered whereas there were no significant changes
      in NGF secretion. We also observed that astrocytic MeCP2 affects the morphology,
      physiology and survival of oligodendrocytes and neurons-two of the key players in
      myelination. Further, we report that some of the axo-glial interaction genes,
      namely Caspr, Notch1, Nf155 and Nrg1 are under the regulation of astrocytic MeCP2
      along with key myelin genes and proteins.

PMID- 30116867
TI  - Ossification of the posterior longitudinal ligament in the cervical spine: a
      review.
AB  - Ossification of the posterior longitudinal ligament (OPLL) is a rare pathologic
      process of lamellar bone deposition that can result in spinal cord compression.
      While multiple genetic and environmental factors have been related to the
      development of OPLL, the pathophysiology remains poorly understood. Asymptomatic
      patients may be managed conservatively and patients with radiculopathy or
      myelopathy should be considered for surgical decompression. Multiple studies have
      demonstrated the morphology and size of the OPLL as well as the cervical
      alignment have significant implications for the appropriate surgical approach and
      technique. In this review, we aim to address all the available literature on the
      etiology, history, presentation, and management of OPLL in an effort to better
      understand OPLL and give our recommendations for the treatment of patients
      presenting with OPLL.

PMID- 30116868
TI  - Comment on Smeets et al.: 'The patellar pubic percussion test: a simple bedside
      tool for suspected occult hip fractures'.

PMID- 30116869
TI  - Effect of reduction quality on post-operative outcomes in 31-A2 intertrochanteric
      fractures following intramedullary fixation: a retrospective study based on
      computerised tomography  findings.
AB  - PURPOSE: To determine how the reduction of medial and anteromedial cortices using
      CT findings in 31-A2 intertrochanteric fractures treated with the intramedullary
      nail could affect the clinical outcomes and complication rates of the fractures.
      METHODS: We retrospectively analyzed the data of 43 patients with 31-A2
      intertrochanteric fractures who underwent closed reduction and intramedullary
      internal fixation (CRIF) between January 2010 and December 2013. Patients were
      classified into two groups based on the post-operative CT scans taken from the
      sagittal and coronal planes, respectively. Five radiographic parameters and three
      clinical parameters were used to evaluate the post-operative functional states
      and mobilization levels in this study. Post-operative complications were also
      recorded. RESULTS: The mean loss of the femoral neck-shaft angle (FNSA) was
      significantly smaller in Group C1 than that in Group C2. There were significant
      differences in the sliding distance of the cephalic nail and the loss of femoral
      head height between the two groups. In terms of the reduction conditions shown on
      the sagittal planes, the FNSA, sliding distance of the cephalic nail, and the
      loss of FHH were significantly different, although differences in TCD were not
      significant. Patients in groups C1 (3.6%) and S1 (0.0%) had lower complication
      rates compared to patients in groups C2 (26.7%) and S2 (27.8%). CONCLUSION:
      Patients with good reduction quality of the medial and anteromedial sustainable
      cortices had better clinical outcomes and lower complication rates. The
      sustainable stability and anti-rotational function of these validated reductions
      might play a critical role in maintaining the fragment positions and reducing the
      incidence of complications in patients.

PMID- 30116870
TI  - Complications with the clavicle hook plate after fixation of Neer type II
      clavicle fractures.
AB  - BACKGROUND AND PURPOSE: There is no consensus on the optimal surgical procedure
      for treating Neer type-2 distal clavicle fractures. Hook plates provide better
      stability than other fixation methods for small fragments but have been related
      to multiple complications. METHODS: Retrospective study on patients operated for
      Neer type-2 fractures using a hook plate. At the time of the study, we performed
      functional (UCLA and Constant scales) and radiographic (coracoclavicular distance
      CCD) evaluation and ultrasound assessments of the condition of the rotator cuff.
      RESULTS: Twenty-four patients were included in the study, with a mean age of 43
      years (18-81) and a mean follow-up of 40.4 months (22-67). All the fractures
      healed, except one. The plate was removed at a mean of five  months (3-13). The
      Constant score was 85.7 and the UCLA score was 32. The mean increase in CCD at
      final follow-up was 9.6% +/- 7.2% (range 1.9-54.3%) compared with the uninjured
      side. Nine patients showed acromioclavicular arthrosis (only one case was
      symptomatic), and 12% showed subacromial osteolysis. No acromion fractures were
      recorded. The implant failed in three cases due to medial movement of the
      material, and we found one peri-plate fracture. CONCLUSIONS: The use of hook
      plates in this particular type of fracture provides high consolidation rates and
      good functional outcomes, irrespective of the fracture subtype. However, it is
      essential to select the correct length and depth of the hook to prevent
      complications such as medial movement of the implant. Ultrasound assessment
      showed that rotator cuff injury is not a common complication if the implant is
      removed as soon as the fracture has consolidated.

PMID- 30116873
TI  - Radiomics in esophageal and gastric cancer.
AB  - Esophageal, esophago-gastric, and gastric cancers are major causes of cancer
      morbidity and cancer death. For patients with potentially resectable disease,
      multi-modality treatment is recommended as it provides the best chance of
      survival. However, quality of life may be adversely affected by therapy, and with
      a wide variation in outcome despite multi-modality therapy, there is a clear need
      to improve patient stratification. Radiomic approaches provide an opportunity to
      improve tumor phenotyping. In this review we assess the evidence to date and
      discuss how these approaches could improve outcome in esophageal, esophago
      gastric, and gastric cancer.

PMID- 30116872
TI  - Persistent peripheral blood EBV-DNA positive with high expression of PD-L1 and
      upregulation of CD4 + CD25 + T cell ratio in early stage NK/T cell lymphoma
      patients may predict worse outcome.
AB  - Although gemcitabine, oxaliplatin and L-asparaginase/pegylated asparaginase (P
      GEMOX) treatment for early-stage extranodal natural killer/T cell lymphoma
      (ENKTL) is effective, some patients die within 1 year of diagnosis. We attempted
      to determine an optimal biomarker for identifying such patients. We enrolled 71
      patients with ENKTL who received P-GEMOX between January 2011 and January 2014.
      We classified the patients according to the outcome into worse (died within 1
      year) or better groups (survival time >= 3, 4 or 5 years). The area under the
      curve (AUC) was determined to identify the optimal biomarker for differentiating
      the groups. The AUC was highest in patients who were plasma Epstein-Barr virus
      (EBV) DNA-positive post-treatment. The AUC was 0.82, 0.86 and 0.86 when the worse
      group was compared to the better group, respectively. Among the post-treatment
      EBV DNA-positive patients, as compared to EBV DNA-negative patients, pre
      treatment EBV DNA-positive patients had a higher proportion of CD4 + CD25 + T
      cells. There was higher programmed cell death protein ligand-1(PD-L1) expression
      in post-treatment EBV DNA-positive patients. Post-treatment positive EBV DNA
      status maybe a useful biomarker of worse outcomes in early stage ENKTL.

PMID- 30116874
TI  - Venetian blind shadowing on ultrasound.

PMID- 30116871
TI  - Posttransplant monomorphic Burkitt's lymphoma: clinical characteristics and
      outcome of a multicenter series.
AB  - Burkitt's monomorphic posttransplant lymphoproliferative disorder (B-PTLD) is an
      uncommon subtype of PTLD. Owing to the paucity of this complication, clinical
      characteristics and outcome has not been fully described. Clinical
      characteristics and outcomes of 20 patients diagnosed with B-PTLD from 10
      transplant centers belonging to the GEL/TAMO group were reviewed. Median time
      from transplant to B-PTLD was 7.2 years. All the cases fulfill the morphologic
      and genetic criteria of B-PTLD, whereas Epstein-Barr virus (EBV) was detected in
      70% of cases. Patients were treated with different chemotherapy combinations, and
      three patients received upfront rituximab monotherapy. The great majority of
      patients receiving CHOP-like regimens attained a complete response (CR) (73%),
      similar to that obtained with dose-intensive chemotherapy (83% CR). In contrast,
      patients receiving upfront rituximab monotherapy required subsequent
      chemotherapy. Two patients (10%) died during treatment due to infection. The
      median progression-free survival and overall survival (OS) were 16 months and 139
      months, respectively. When analyzing variables predicting for OS, we found that
      patients with bone marrow involvement had an adverse prognosis, with a median OS
      of 6 months (p = 0.008). In conclusion, B-PTLD is an uncommon complication
      usually associated with EBV infection and with an aggressive clinical course,
      particularly in patients with bone marrow involvement. High-dose
      chemoimmunotherapy obtained similar responses to R-CHOP, suggesting that R-CHOP
      could be an adequate alternative for these patients. In contrast, rituximab
      monotherapy does not seem to be effective enough to control the disease.

PMID- 30116875
TI  - Rediscovery of Culex (Neoculex) martinii Medschid, 1930 (Diptera, Culicidae) in
      Germany.
AB  - The culicid Culex martinii is an extremely rare species in Germany, with only one
      reference in the scientific literature, according to which larvae were found once
      in 1935 in the eastern part of the country. During regular mosquito sampling
      activities with BG-Sentinel traps, Cx. martinii was rediscovered in autumn 2017
      at one location in the German federal state of Thuringia. Prompted by this
      finding, the Peus mosquito collection at the Senckenberg Museum Frankfurt was
      checked for further specimens of this species. Indeed, it contained Cx. martinii
      specimens from two sites in southern Germany from 1973 in addition to the
      published finding from 1935 and further specimens from that latter site from 1936
      and 1951. Due to its rarity, little is known on the ecology of Cx. martinii and
      nothing on a possible vector role.

PMID- 30116876
TI  - Predation by avian insectivores on caterpillars is linked to leaf damage on oak
      (Quercus robur).
AB  - Birds that are foraging in tree canopies can cause a substantial decrease in
      arthropod numbers. Trees may benefit from avian insectivores attacking insect
      herbivores. In a field study, we tested whether the intensity of bird predation
      on caterpillars is linked quantitatively to leaf damage caused by insect
      herbivores, a hypothesized relationship that previously was poorly investigated.
      Artificial caterpillars were placed in the lower part of oak trees (Quercus
      robur) in urban and suburban sites across the city of Gothenburg, Sweden. Two
      days later, we recorded the survival: the pooled predation rate was 11.5% (5.7%
      day-1). Mean predation rate per tree was 10.4%. Mean leaf damage, i.e. leaf area
      eaten by insect herbivores, per tree was 5.7% but there was large variation
      between trees. We found a significant negative relationship between survival
      probability of caterpillars and leaf damage in an analysis using a mixed model
      logistic regression. This suggests that caterpillars are at high risk of bird
      attacks in trees with a high degree of leaf damage and avian insectivores may
      increase the foraging effort in the foliage of such oak trees. Our findings
      concerning the quantitative relationship between the predator-prey interactions
      and plant damage suggested tentatively that the survival probability of
      caterpillars decreases rapidly at 15-20% leaf damage in lower part of oak
      canopies. Furthermore, our findings add credence to the idea of using artificial
      caterpillars as a means to obtain standardized comparisons of predation rates in
      various habitats.

PMID- 30116877
TI  - Population response of an apex Antarctic consumer to its prey and climate
      fluctuations.
AB  - A fundamental endeavor in population ecology is to identify the drivers of
      population dynamics. A few empirical studies included the effect of prey
      abundance when investigating simultaneously the effects of density-dependence and
      climate factors on marine top-predator population dynamics. Our aim was to
      unravel the mechanisms forcing population dynamics of an apex consumer seabird,
      the south polar skua, using long-term climatic and population time series of the
      consumer and its prey in Terre Adelie, Antarctica. Influences of density
      dependence, climatic factors, and prey abundance with lag effects were tested on
      the breeding population dynamics with a Bayesian multi-model inference approach.
      We evidenced a negative trend in breeding population growth rate when density
      increased. Lagged effects of sea-ice concentration and air temperature in spring
      and a contemporary effect of prey resources were supported. Remarkably, results
      outline a reverse response of the south polar skua and one of its main preys to
      the same environmental factor (sea-ice concentration), suggesting a strong link
      between skua and penguin dynamics. The causal mechanisms may involve competition
      for food and space through territorial behavior as well as local climate and prey
      availability, which probably operate on breeding parameters (breeding propensity,
      breeding success, or recruitment) rather than on adult survival. Our results
      provide new insights on the relative importance of factors forcing the population
      dynamics of an apex consumer including density-dependence, local climate
      conditions, and direct and indirect effects of prey abundance.

PMID- 30116878
TI  - Self-perception of quality of life in patients with functional voice disorders:
      the effects of psychological and vocal acoustic variables.
AB  - PURPOSE: Functional voice disorders (FVD) are multifactorial and may have a
      significant impact on the patients' quality of life (QOL). The aim of this study
      was to explore and analyze the relationship between the VHI scores, psychological
      variables, and objective voice measurements, and to develop a psychological
      and/or vocal acoustic model for the overall self-perceived evaluation of quality
      of life for three different types of FVD. METHODS: After ENT examination, 83
      women were classified into three groups: psychogenic voice disorder (PVD = 39),
      primary muscle tension voice disorder (MTVD1 = 16), and secondary muscle tension
      voice disorder (MTVD2 = 28). All patients were evaluated according to a
      multidisciplinary assessment protocol, which included the self-evaluation of
      quality of life (Voice Handicap Index, VHI), psychological evaluation (Hamilton
      Rating Scales for Depression (HAM-D) and for Anxiety (HARS), and Temperament
      Evaluation of Memphis, Pisa, Paris and San Diego-Auto questionnaire (TEMPS-A)),
      and vocal acoustic analysis [mean fundamental frequency (F0, Hz), jitter (local,
      %), shimmer (local, %), and harmonic-to-noise ratio (HNR, dB)]. RESULTS: Our
      findings revealed a moderate impact on QOL, regardless of the type of FVD. There
      were significant correlations between VHI scores, psychological variables, and
      voice perturbation parameters, with the exception of the MTVD1 and MTVD2 groups.
      The stepwise multiple linear regression analysis suggested that QOL could be
      explained by: anxious temperament together with shimmer in PVD group, jitter in
      the MTVD1 group, and depressive temperament in the MTVD2 group. CONCLUSIONS:
      Affective temperaments and/or voice perturbation parameters were meaningful
      predictors of self-evaluation of quality of life in patients with different types
      of FVD.

PMID- 30116880
TI  - Brief report: length of ileal resection correlates with severity of bile acid
      malabsorption in Crohn's disease.
AB  - PURPOSE: Bile acid malabsorption (BAM) is a common cause of diarrhoea in Crohn's
      disease (CD) patients with ileal resection. BAM is usually diagnosed by selenium
      labelled homotaurocholic acid test (75SeHCAT) but its availability is limited.
      Consequently, a large proportion of patients either remain undiagnosed or subject
      to empirical therapy. There is a paucity of studies examining the correlation
      between length of ileal resection and severity of BAM, which will be of use to
      clinicians with no recourse to diagnostic testing for BAM. METHODS: We tested the
      correlation between length of resected ileum and percentage retention on 75SeHCAT
      of all CD patients with a prior surgical resection who underwent 75SeHCAT
      testing. Response to treatment with bile salt sequestrant and 75SeHCAT retention
      values was tested using Fisher's exact test. RESULTS: A total of 91 patients were
      identified with a median age of 47 (IQR 21-80). The median length of resected
      ileum was 24 cm (range 15-165 cm) with a median of 1 resection (range 1-4).
      Overall, 88 patients (97%) had 75SeHCAT retention values of < 10% and 85 (93%)
      had retention of < 5%. There was a modest correlation between 75SeHCAT retention
      and length of ileal resection (Spearman's rho - 0.392, P = 0.0001). Data on
      response to treatment was available for 57 (63%) patients, of who 38 (67%)
      responded to bile salt sequestrant. There was no difference in 75SeHCAT retention
      values between responders and non-responders. CONCLUSIONS: There was a modest
      correlation between length of ileal resection and severity of BAM as defined by
      75SeHCAT retention values. Response to bile salt sequestrant therapy was not
      dependent on 75SeHCAT retention values.

PMID- 30116879
TI  - Current practice in the surgical management of parathyroid disorders: a United
      Kingdom survey.
AB  - PURPOSE: Surgery for primary hyperparathyroidism is undertaken by many
      specialties but predominantly endocrine and ear, nose and throat (ENT) surgeons.
      There is currently no consensus on the peri-operative management of primary
      hyperparathyroidism. We sought to determine current surgical practice and
      identify any inter-specialty variation in the United Kingdom (UK). METHODS: An
      online survey was disseminated to members of the British Association of Endocrine
      & Thyroid Surgeons (BAETS) in the UK. RESULTS: 78 surgeons responded (40
      Endocrine, 37 ENT and 1 maxillofacial). 90% of surgeons used ultrasound and
      sestamibi for pre-operative localisation. Intraoperative frozen section (31%) and
      parathyroid hormone monitoring (41%) were the most common adjuncts used
      intraoperatively. 68% of surgeons did not use any wound drains. Nearly two-thirds
      of surgeons (64%) discharged patients from the clinic within 3 months, There were
      some significant differences (p < 0.05) in particular areas of practice between
      endocrine and ENT surgeons (%, p): use of single-photon emission computed
      tomography (SPECT) (Endocrine 25% vs. ENT 5%), preoperative laryngeal assessment
      (endocrine 58% vs. ENT 95%), intraoperative laryngeal nerve monitoring (endocrine
      35% vs. ENT 68%), use of monopolar diathermy (endocrine 58% vs. ENT 22%), bipolar
      diathermy (endocrine 60% vs. 89%) and surgical ties (endocrine 48% vs. ENT 19%).
      CONCLUSION: Our study demonstrates some similarities as well as some notable
      differences in practice between endocrine and ENT surgeons, and therefore,
      highlights the need for national consensus with respect to some key areas in
      parathyroid surgery.

PMID- 30116881
TI  - Enumeration of compact coalescent histories for matching gene trees and species
      trees.
AB  - Compact coalescent histories are combinatorial structures that describe for a
      given gene tree G and species tree S possibilities for the numbers of
      coalescences of G that take place on the various branches of S. They have been
      introduced as a data structure for evaluating probabilities of gene tree
      topologies conditioning on species trees, reducing computation time compared to
      standard coalescent histories. When gene trees and species trees have a matching
      labeled topology [Formula: see text], the compact coalescent histories of t are
      encoded by particular integer labelings of the branches of t, each integer
      specifying the number of coalescent events of G present in a branch of S. For
      matching gene trees and species trees, we investigate enumerative properties of
      compact coalescent histories. We report a recursion for the number of compact
      coalescent histories for matching gene trees and species trees, using it to study
      the numbers of compact coalescent histories for small trees. We show that the
      number of compact coalescent histories equals the number of coalescent histories
      if and only if the labeled topology is a caterpillar or a bicaterpillar. The
      number of compact coalescent histories is seen to increase with tree imbalance:
      we prove that as the number of taxa n increases, the exponential growth of the
      number of compact coalescent histories follows [Formula: see text] in the case of
      caterpillar or bicaterpillar labeled topologies and approximately [Formula: see
      text] and [Formula: see text] for lodgepole and balanced topologies,
      respectively. We prove that the mean number of compact coalescent histories of a
      labeled topology of size n selected uniformly at random grows with [Formula: see
      text]. Our results contribute to the analysis of the computational complexity of
      algorithms for computing gene tree probabilities, and to the combinatorial study
      of gene trees and species trees more generally.

PMID- 30116882
TI  - Generalizing a mathematical model of prion aggregation allows strain coexistence
      and co-stability by including a novel misfolded species.
AB  - Prions are proteins capable of adopting misfolded conformations and transmitting
      these conformations to other normally folded proteins. Prions are most commonly
      known for causing fatal neurodegenerative diseases in mammals but are also
      associated with several harmless phenotypes in yeast. A distinct feature of prion
      propagation is the existence of different phenotypical variants, called strains.
      It is widely accepted that these strains correspond to different conformational
      states of the protein, but the mechanisms driving their interactions remain
      poorly understood. This study uses mathematical modeling to provide insight into
      this problem. We show that the classical model of prion dynamics allows at most
      one conformational strain to stably propagate. In order to conform to biological
      observations of strain coexistence and co-stability, we develop an extension of
      the classical model by introducing a novel prion species consistent with
      biological studies. Qualitative analysis of this model reveals a new variety of
      behavior. Indeed, it allows for stable coexistence of different strains in a wide
      parameter range, and it also introduces intricate initial condition dependency.
      These new behaviors are consistent with experimental observations of prions in
      both mammals and yeast. As such, our model provides a valuable tool for
      investigating the underlying mechanisms of prion propagation and the link between
      prion strains and strain specific phenotypes. The consideration of a novel prion
      species brings a change in perspective on prion biology and we use our model to
      generate hypotheses about prion infectivity.

PMID- 30116884
TI  - Validation of the German Version of the Yale Pharyngeal Residue Severity Rating
      Scale.
AB  - The aim of this study was to validate the German Version of the Yale Pharyngeal
      Residue Severity Rating Scale and to investigate the impact of rater experience
      and training. The English original scale was translated into German language
      using a forward-backward method. For the validation, 30 images of different
      pharyngeal residue amounts have been selected and assigned to the scales'
      severity levels by two experts. 28 raters rated the images in randomized order in
      two passes. To investigate the impact of experience and training, raters were
      grouped into subgroups. Statistical analysis was carried out using kappa
      statistics. The results demonstrate excellent residue ratings for construct
      validity, inter-rater reliability and intra-rater reliability regarding overall
      group and all subgroups (Kappa > 0.90). No significant differences were found
      between groups by experience and inconstant differences were found between groups
      by training. The German version of the Yale Pharyngeal Residue Severity Rating
      Scale is a valid, reliable instrument for scoring location and severity of
      pharyngeal residue in the context of flexible endoscopic evaluations of
      swallowing.

PMID- 30116883
TI  - The roles of PKCs in regulating autophagy.
AB  - PURPOSE: Autophagy, as a highly conserved cellular degradation and recycling
      process, plays an important part in maintaining cellular homeostasis. PKC
      signaling is involved in multiple pathways including cell cycle progression,
      tumorigenesis, migration and autophagy. METHODS: Literatures about PKC and
      autophagy from PubMed databases were reviewed in this study. RESULTS: Studies
      regarding the association of PKC and autophagy remain debatable. Different
      duration of the stimulation of autophagy and distinct cell contexts result in
      different function of PKC in regulating autophagy. The subcellular localization
      of PKCs and their downstream regulators may influence the autophagy regulation as
      well. As important intracellular components, the mitochondria play an important
      role in regulating autophagy, by metabolic modulation and structural derangement.
      CONCLUSION: Phase II studies regarding PKC-beta inhibitor, enzastaurin, showed
      promising results in MCL, DLBCL and recurrent high-grade gliomas. However, the
      detailed mechanism is still in need. The mechanism of PKC-beta in mediating
      autophagy in lymphoma and high-grade gliomas remains elusive as well. Moreover,
      several studies were in agreement that rottlerin enhanced autophagy in breast
      cancer cells, which warrants further clinical studies to verify PKC-delta as a
      therapeutic target. Thus, identifying the function of PKC in modulating autophagy
      and conducting related clinical studies help find novel target for chemotherapy.

PMID- 30116886
TI  - Effects of pitch and tempo of auditory rhythms on spontaneous movement
      entrainment and stabilisation.
AB  - Human movements spontaneously entrain to auditory rhythms, which can help to
      stabilise movements in time and space. The properties of auditory rhythms
      supporting the occurrence of this phenomenon, however, remain largely unclear.
      Here, we investigate in two experiments the effects of pitch and tempo on
      spontaneous movement entrainment and stabilisation. We examined spontaneous
      entrainment of hand-held pendulum swinging in time with low-pitched (100 Hz) and
      high-pitched (1600 Hz) metronomes to test whether low pitch favours movement
      entrainment and stabilisation. To investigate whether stimulation and movement
      tempi moderate these effects of pitch, we manipulated (1) participants' preferred
      movement tempo by varying pendulum mechanical constraints (Experiment 1) and (2)
      stimulation tempo, which was either equal to, or slightly slower or faster (+/-
      10%) than the participant's preferred movement tempo (Experiment 2). The results
      showed that participants' movements spontaneously entrained to auditory rhythms,
      and that this effect was stronger with low-pitched rhythms independently of
      stimulation and movement tempi. Results also indicated that auditory rhythms can
      lead to increased movement amplitude and stabilisation of movement tempo and
      amplitude, particularly when low-pitched. However, stabilisation effects were
      found to depend on intrinsic movement variability. Auditory rhythms decreased
      movement variability of individuals with higher intrinsic variability but
      increased movement variability of individuals with lower intrinsic variability.
      These findings provide new insights into factors that influence auditory-motor
      entrainment and how they may be optimised to enhance movement efficiency.

PMID- 30116887
TI  - Evaluation of the protective role of exogenous growth regulators against Ni
      toxicity in woody shrub Daphne jasminea.
AB  - MAIN CONCLUSION: The results provide a significant verification of the activity
      of exogenously applied phytohormones: gibberellic acid, jasmonic acid, and
      brassinolide in the modulation of the plant's response to nickel treatment. The
      study investigated nickel accumulation and its toxicity to Daphne jasminea shoots
      cultured in vitro with or without exogenous supplementation with phytohormones:
      gibberellic acid (GA3), jasmonic acid (JA), and brassinolide (BL). The aim was to
      verify the modulatory effect of exogenous plant growth regulators (PGRs) on plant
      reaction to Ni excess. The combined action of Ni and PGRs was evaluated at the
      anatomical, ultrastructural, and biochemical levels. Nickel toxicity was
      manifested in decreased biomass accretion and growth tolerance index (83-53.6%),
      attributed to enhanced synthesis of growth inhibitors, mainly abscisic acid. As a
      defence reaction, endogenous gibberellins accumulated. Exogenous GA3 ameliorated
      the plant reaction to Ni stress, inducing proliferation and growth rate. Ni
      tolerance in the presence of GA3 was attributed to peroxisomal reactions that
      stimulated the synthesis of endogenous JA. In contrast, the application of BL
      caused enhanced Ni accumulation. Plants suffered from pronounced stress due to
      massive oxidation. The defence strategy of plants subjected to Ni and BL involved
      cell wall rearrangements. Exogenous JA stimulated the synthesis of active auxins
      and salicylic acid, contributing to enhanced mitotic activity within explants.
      However, JA disturbed the integrity of chloroplasts and lamellar compartments.
      Our study revealed that an action of exogenous PGRs may either enhance tolerance
      to Ni or increase metal toxicity in D. jasminea. Particularly in in vitro
      culture, where explants are subjected to external phytohormonal stimuli, the
      combined effects of supplemental PGRs may enhance stress and substantially affect
      plant development. Our results provide a significant verification of exogenous
      PGRs activity in the modulation of plant response to nickel.

PMID- 30116885
TI  - Human genetics of mycobacterial disease.
AB  - Mycobacterial diseases are caused by members of the genus Mycobacterium, acid
      fast bacteria characterized by the presence of mycolic acids within their cell
      walls. Claiming almost 2 million lives every year, tuberculosis (TB) is the most
      common mycobacterial disease and is caused by infection with M. tuberculosis and,
      in rare cases, by M. bovis or M. africanum. The second and third most common
      mycobacterial diseases are leprosy and buruli ulcer (BU), respectively. Both
      diseases affect the skin and can lead to permanent sequelae and deformities.
      Leprosy is caused by the uncultivable M. leprae while the etiological agent of BU
      is the environmental bacterium M. ulcerans. After exposure to these mycobacterial
      species, a majority of individuals will not progress to clinical disease and,
      among those who do, inter-individual variability in disease manifestation and
      outcome can be observed. Susceptibility to mycobacterial diseases carries a human
      genetic component and intense efforts have been applied over the past decades to
      decipher the exact nature of the genetic factors controlling disease
      susceptibility. While for BU this search was mostly conducted on the basis of
      candidate genes association studies, genome-wide approaches have been widely
      applied for TB and leprosy. In this review, we summarize some of the findings
      achieved by genome-wide linkage, association and transcriptome analyses in TB
      disease and leprosy and the recent genetic findings for BU susceptibility.

PMID- 30116888
TI  - Immunohistochemical and selected genetic reflex testing of all uterine
      leiomyosarcomas and STUMPs for ALK gene rearrangement may provide an effective
      screening tool in identifying uterine ALK-rearranged mesenchymal tumors.
AB  - We examined the value of targeted molecular screening for the identification of
      uterine anaplastic lymphoma kinase (ALK)-rearranged mesenchymal tumors, including
      ALK immunohistochemistry followed by molecular genetic testing, in all uterine
      leiomyosarcomas and STUMPs (smooth muscle tumors of uncertain malignant
      potential). All leiomyosarcoma and STUMP cases diagnosed in a 10-year period
      (2006-2016) at Charles University Faculty of Medicine in Pilsen were retrieved
      and reviewed. Of 23 cases, one case (LMS [leiomyosarcoma]) was positive for ALK
      rearrangement, namely, PPP1CB-ALK fusion gene. No specific histologic features
      (i.e., lymphocytic infiltrate and stromal edema) were observed in this case. This
      suggests that inflammatory myofibroblastic tumor (IMT)-like histologic features
      may not be an initial reliable screening tool in identifying uterine IMT cases.
      Thus, we proposed a two-step IHC and molecular genetic testing (as a reflex test)
      for IMT in all uterine LMS and STUMP cases. This will enhance the proper
      detection of such tumors at the population level and ultimately offer patients
      available targeted therapies.

PMID- 30116890
TI  - Reflex regulation of breathing by the paratrigeminal nucleus via multiple bulbar
      circuits.
AB  - Sensory neurons of the jugular vagal ganglia innervate the respiratory tract and
      project to the poorly studied medullary paratrigeminal nucleus. In the present
      study, we used neuroanatomical tracing, pharmacology and physiology in guinea pig
      to investigate the paratrigeminal neural circuits mediating jugular ganglia
      evoked respiratory reflexes. Retrogradely traced laryngeal jugular ganglia
      neurons were largely (> 60%) unmyelinated and expressed the neuropeptide
      substance P and calcitonin gene-related peptide, although a population (~ 30%) of
      larger diameter myelinated jugular neurons was defined by the expression of
      vGlut1. Within the brainstem, vagal afferent terminals were confined to the
      caudal two-thirds of the paratrigeminal nucleus. Electrical stimulation of the
      laryngeal mucosa evoked a vagally mediated respiratory slowing that was mimicked
      by laryngeal capsaicin application. These laryngeal reflexes were modestly
      reduced by neuropeptide receptor antagonist microinjections into the
      paratrigeminal nucleus, but abolished by ionotropic glutamate receptor
      antagonists. D,L-Homocysteic acid microinjections into the paratrigeminal nucleus
      mimicked the laryngeal-evoked respiratory slowing, whereas capsaicin
      microinjections evoked a persistent tachypnoea that was insensitive to
      glutamatergic inhibition but abolished by neuropeptide receptor antagonists.
      Extensive projections from paratrigeminal neurons were anterogradely traced
      throughout the pontomedullary respiratory column. Dual retrograde tracing from
      pontine and ventrolateral medullary termination sites, as well as
      immunohistochemical staining for calbindin and neurokinin 1 receptors, supported
      the existence of different subpopulations of paratrigeminal neurons.
      Collectively, these data provide anatomical and functional evidence for at least
      two types of post-synaptic paratrigeminal neurons involved in respiratory
      reflexes, highlighting an unrecognised complexity in sensory processing in this
      region of the brainstem.

PMID- 30116889
TI  - Travelling waves and tonotopicity in the inner ear: a historical and comparative
      perspective.
AB  - In the 1940s, Georg von Bekesy discovered that in the inner ear of cadavers of
      various vertebrates, structures responded to sound with a displacement wave that
      travels in a basal-to-apical direction. This historical review examines this
      concept and sketches its role and significance in the development of the research
      field of cochlear mechanics. It also illustrates that this concept and that of
      tonotopicity necessarily correlate, in that travelling waves are consequences of
      the existence of an ordered, longitudinal array of receptor cells tuned to
      systematically changing frequencies along the auditory organ.

PMID- 30116891
TI  - Glc8, a regulator of protein phosphatase type 1, mediates oxidation tolerance,
      asexual development and virulence in Beauveria bassiana, a filamentous
      entomopathogenic fungus.
AB  - Protein phosphatase type 1 (PP1) plays an important role in cellular metabolism
      and development in yeast. In PP1 enzyme complex, Glc8 protein is a global
      regulatory subunit and regulates many physiological processes. However, its
      biological roles are unexplored in filamentous fungi. In this study, we
      characterized a yeast ortholog of Glc8 in Beauveria bassiana, a filamentous
      entomopathogenic fungus. Gene disruption of BbGlc8 had no significant effect on
      vegetative growth, but resulted in a significant reduction in conidiation (51%)
      and blastospore yield (55%) in the mutant. The DeltaBbGlc8 mutant displayed an
      enhanced sensitivity to oxidative stress and a weakened virulence as indicated by
      cuticle infection and intrahemocoel injection assays. Transcriptomic analysis
      indicated that the genes regulated by BbGlc8 during conidiation were primarily
      associated with metabolism, cell rescue and cell wall formation. Notably, as a
      down-regulated gene in DeltaBbGlc8 mutant, BbOsmC2 (a member of OsmC protein
      family) contributes to fungal resistance to salt stress, spore differentiation
      and virulence. Thus, BbOsmC2 functions as a down-stream target of BbGlc8 during
      spore differentiation, but not in stress response. Our findings indicate that
      BbGlc8 contributes to the biocontrol potential of B. bassiana by mediating
      comprehensive genetic pathways.

PMID- 30116892
TI  - Does a multimethod approach improve identification of medication nonadherence in
      adolescents with chronic kidney disease?
AB  - BACKGROUND: Medical provider assessment of nonadherence is known to be
      inaccurate. Researchers have suggested using a multimethod assessment approach;
      however, no study has demonstrated how to integrate different measures to improve
      accuracy. This study aimed to determine if using additional measures improves the
      accurate identification of nonadherence beyond provider assessment alone.
      METHODS: Eighty-seven adolescents and young adults (AYAs), age 11-19 years, with
      chronic kidney disease (CKD) [stage 1-5/end-stage renal disease (ESRD)] and
      prescribed antihypertensive medication, their caregivers, and 17 medical
      providers participated in the multisite study. Five adherence measures were
      obtained: provider report, AYA report, caregiver report, electronic medication
      monitoring (MEMS), and pharmacy refill data [medication possession ratio (MPR)].
      Concordance was calculated using kappa statistic. Sensitivity, specificity,
      positive predictive power, and negative predictive power were calculated using
      MEMS as the criterion for measuring adherence. RESULTS: There was poor to fair
      concordance (kappas = 0.12-0.54), with 35-61% of AYAs classified as nonadherent
      depending on the measure. While both providers and MEMS classified 35% of the
      AYAs as nonadherent, sensitivity (0.57) and specificity (0.77) demonstrated poor
      agreement between the two measures on identifying which AYAs were nonadherent.
      Combining provider report of nonadherence and MPR < 75% resulted in the highest
      sensitivity for identifying nonadherence (0.90) and negative predictive power
      (0.88). CONCLUSIONS: Nonadherence is prevalent in AYAs with CKD. Providers
      inaccurately identify nonadherence, leading to missed opportunities to intervene.
      Our study demonstrates the benefit to utilizing a multimethod approach to
      identify nonadherence in patients with chronic disease, an essential first step
      to reduce nonadherence.

PMID- 30116894
TI  - Visualization and Bibliometric Analysis of Research Trends on Human Fatigue
      Assessment.
AB  - This study aims to analyze the scientific research progress on human fatigue
      assessment (HFA) by using a bibliometric method, which was conducted a systematic
      analyses of 28,028 scientific papers about HFA from the Web of Science database,
      and the results were discussed from the following perspectives: temporal
      distribution, geographical distribution, discipline distribution, and key words
      distribution. In addition, this analysis also provides the network of author co
      citation and key words. The results are summarized as follows: 1) the number of
      papers about HFA increased rapidly since 1990s; 2) The United States is a high
      yield, high-cited country with 36.70% of the world's total literatures, and whose
      average citation index on HFA research is 47.89 per paper; China is the
      developing country with the largest number of publications, but its total
      citations and average citations are backward, only with an average of 21
      citations per article; 3) The assessment of human fatigue shows the development
      trend of multidisciplinary intersecting; 4) There is a relative lack of
      cooperation among the world's leading scholars; the Dutch Gijs Bleijenberg is the
      most published scholar in the world, who have 108 articles on HFA research; the
      American scholar David Cella has the most influential article, with an h-index of
      36; the distribution of Chinese scholars is relatively scattered, and no one has
      written more than five articles; 5) All of countries in the world had the same
      research topics, "muscle fatigue" is an important part of the HFA; China needs to
      pay more attention to the fatigue assessment associated with cancer. The results
      of the analysis can be used to enhance our understanding of HFA research and
      support further research in this area.

PMID- 30116895
TI  - Antidepressants in breast milk; comparative analysis of excretion ratios.
AB  - Despite increasing prescription rates of antidepressants in pregnant and
      breastfeeding women over the past decades, evidence of drug exposure for neonates
      through lactation is very sparse. Concentrations of three antidepressants
      citalopram, sertraline, and venlafaxine were measured in maternal blood and
      breast milk in 17 women receiving antidepressant therapy during breastfeeding
      period. We also computed concentration-by-dose-ratios (C/D) and milk to serum
      (plasma) penetration ratios (M/P). Non-parametric tests were applied. Serum
      concentration of citalopram and daily dosage correlated positively while daily
      dosage and mother milk concentration did not (rho = 0.939, p = 0.005, and rho =
      0.772, p > 0.05 respectively). A significant correlation was also found between
      serum and milk concentrations (rho = 0.812, p = 0.05). Venlafaxine daily dosage
      correlated positively with the active moiety milk concentration (rho = 0.949, p =
      0.014). No significant correlations were reported for sertraline. The amount of
      antidepressant concentrations to which neonates may be exposed, assessed as
      absolute infant dose (AID), was particularly low with the highest median AID
      being 0.16 mg/kg/day for venlafaxine. No significant difference was detected for
      the M/P ratios between different drugs (p > 0.05), whereas the comparison of C/D
      ratios revealed lower values in the sertraline group, with the highest values
      reported for citalopram group (p = 0.007 for serum concentrations and p = 0.008
      for mother milk). Findings suggest that breastfeeding under antidepressant
      treatment constantly exposes children with measurable drug concentrations. As
      daily dosage and serum concentration of the antidepressants did not predict drug
      concentrations in mother milk, measuring of drug concentrations in milk helps to
      quantify drug exposure during breastfeeding. More data-even data of drug
      concentrations in breastfed children-are needed to better assess the effects of
      drug exposure on children's development.

PMID- 30116896
TI  - Interventions for the prevention of postpartum depression in adolescent mothers:
      a systematic review.
AB  - Postpartum depression (PPD) is a major public health problem affecting 10-57% of
      adolescent mothers which can affect not only adolescent mothers but also their
      infants. Thus, there is a need for interventions to prevent PPD in adolescent
      mothers. However, recent systematic reviews have been focused on effective
      interventions to prevent PPD in adult mothers. These interventions may not
      necessarily be applicable for adolescent mothers. Therefore, the purpose of this
      review was to examine the effectiveness of the existing interventions to prevent
      PPD in adolescent mothers. A systematic search was performed in MEDLINE, CINAHL,
      and SCOPUS databases between January 2000 and March 2017 with English language
      and studies involving human subjects. Studies reporting on the outcomes of
      intervention to prevent PPD particularly in adolescent mothers were selected. Non
      comparative studies were excluded. From 2002 identified records, 13 studies were
      included, reporting on 2236 adolescent pregnant women. The evidence from this
      systematic review suggests that 6 of 13 studies from both psychological and
      psychosocial interventions including (1) home-visiting intervention, (2) prenatal
      antenatal and postnatal educational program, (3) CBT psycho-educational, (4) the
      REACH program based on interpersonal therapy, and (5) infant massage training is
      successful in reducing rates of PPD symptoms in adolescent mothers in the
      intervention group than those mothers in the control group. These interventions
      might be considered for incorporation in antenatal care interventions for
      adolescent pregnant women. However, this review did not find evidence identifying
      the most effective intervention for preventing postpartum depression symptoms in
      adolescent mothers.

PMID- 30116893
TI  - Transcripts of Kv7.1 and MinK channels and slow delayed rectifier K+ current
      (IKs) are expressed in zebrafish (Danio rerio) heart.
AB  - Zebrafish are increasingly used as a model for human cardiac electrophysiology,
      arrhythmias, and drug screening. However, K+ ion channels of the zebrafish heart,
      which determine the rate of repolarization and duration of cardiac action
      potential (AP) are still incompletely known and characterized. Here, we provide
      the first evidence for the presence of the slow component of the delayed
      rectifier K+channels in the zebrafish heart and characterize electrophysiological
      properties of the slow component of the delayed rectifier K+current, IKs.
      Zebrafish atrium and ventricle showed strong transcript expression of the kcnq1
      gene, which encodes the Kv7.1 alpha-subunit of the slow delayed rectifier K+
      channel. In contrast, the kcne1 gene, encoding the MinK beta-subunit of the
      delayed rectifier, was expressed at 21 and 17 times lower level in ventricle and
      atrium, respectively, in comparison to the kcnq1. IKs was observed in 62% of
      ventricular myocytes with mean (+/- SEM) density of 1.23 +/- 0.37 pA/pF at + 30
      mV. Activation rate of IKs was 38% faster (tau50 = 1248 +/- 215 ms) than
      kcnq1:kcne1 channels (1725 +/- 792 ms) expressed in 3:1 ratio in Chinese hamster
      ovary cells. Microelectrode experiments demonstrated the functional relevance of
      IKs in the zebrafish heart, since 100 MUM chromanol 293B produced a significant
      prolongation of AP in zebrafish ventricle. We conclude that AP repolarization in
      zebrafish ventricle is contributed by IKs, which is mainly generated by
      homotetrameric Kv7.1 channels not coupled to MinK ancillary beta-subunits. This
      is a clear difference to the human heart, where MinK is an essential component of
      the slow delayed rectifier K+channel.

PMID- 30116897
TI  - Impedimetric gene assay for BCR/ABL transcripts in plasmids of patients with
      chronic myeloid leukemia.
AB  - A label-free impedimetric biosensor was developed for determination of BCR/ABL
      transcripts. Specific DNA primers were covalently immobilized on a gold electrode
      modified with carboxylated multiwalled carbon nanotubes (cMWCNTs) and zinc oxide
      nanoparticles (ZnO-NPs). Aggregation of the ZnO-NPs is prevented by the
      introduction of an amino-modified silica coating, which also allows a subsequent
      covalent linkage to cMWCNTs. The impedimetric biosensor was typically operated at
      a working voltage of +10 mV vs. Ag/AgCl, in a frequency range from 100 mHz to 100
      kHz. Studies on the surface morphology and electrochemical properties of the
      electrode demonstrated improved bioactivity. Amperometric currents and
      impedimetric parameters, such as charge transfer resistance, varied significantly
      throughout the construction of the biosensor. The hybridization process was also
      evidenced by changes in the topography of the surface after exposure to samples
      containing BCR/ABL. The gene sensor has a linear concentration range for the
      target gene of 6.94 aM to 694 fM with a limit of detection as low as 0.039 aM.
      Also, the biosensor is selective and reproducible with a standard deviation of
      4.1%. Three replicates for each experimental condition were used. Hence, it is
      perceived to be a viable tool for early-stage diagnosis of the BCR/ABL fusion
      gene and monitoring of major molecular remission in clinical samples. Graphical
      abstract Schematic of a highly sensitive hybridization assay for the BCR/ABL
      fusion gene. It is based on ZnO nanoparticle functionalized with 3
      (aminopropyl)triethoxysilane.

PMID- 30116898
TI  - Hemodynamic Solution Computation and Pathological Analysis in the Circle of
      Willis.
AB  - Hemodynamic indexes will change significantly compared to the normal range of
      many vascular diseases, therefore it is necessary to establish hemodynamic
      computation model. Blood circulation is periodically forced huge fluid flow
      network, the heart is generator of the entire fluid network, based on this
      hemodynamic characteristics, the circle of Willis's structure is simplified from
      the perspective of network and hemodynamics. According to hemodynamic equations
      and circuit graph theory, models blood flow network of the periodically forced
      hemodynamic equation, obtains the approximate solution of the harmonic waves form
      based on averaging computation. We apply this model in the network of the circle
      of Willis, which may help explain the development processes of cerebral
      circulation disease. The simulation results show that computing results
      consistent with the clinical observation of blood flow changes in cerebral
      infarction.

PMID- 30116899
TI  - Correction to: Air quality and passenger comfort in an air-conditioned bus micro
      environment.
AB  - The original version of this article unfortunately contained an error in the
      affiliation section and an error of the email address of corresponding author.

PMID- 30116901
TI  - Electrochemical synthesis of a nanocomposite consisting of carboxy-modified multi
      walled carbon nanotubes, polythionine and platinum nanoparticles for simultaneous
      voltammetric determination of myricetin and rutin.
AB  - The authors describe a method for electrochemical synthesis of a nanocomposite
      consisting of carboxylated multi-walled carbon nanotubes, polythionine and
      platinum nanoparticles (denoted as cMWCNT@pTh@Pt). The composite was placed on a
      glassy carbon electrode (GCE) to obtain a sensor for simultaneous determination
      of myricetin and rutin by differential pulse voltammetry, with typical peak
      voltages of 0.16 and 0.34 V (vs. SCE). Under optimal conditions, the modified GCE
      has a linear response in the range of 0.01-15 MUM myricetin concentration range,
      and a 3 nM lower detection limit. For rutin, the data are 0.01-15 MUM and 1.7 nM,
      respectively. The sensor is selective, stable and reproducible. It was
      successfully applied to the simultaneous determination of myricetin and rutin in
      spiked juice samples, and satisfactory results were obtained. Graphical abstract
      A nanocomposite consists of carboxy multi-walled carbon nanotube (cMWCNT),
      polythionine (pTh) and platinum nanoparticles (Pt) was presented for the
      simultaneous determination of myricetin and rutin. The nanocomposite shows
      excellent electrochemical determination performances based on a synergistic
      effect among cMWCNT, pTh and Pt.

PMID- 30116900
TI  - Water quality characteristics and corrosion potential in blending zones in X city
      drinking water distribution system.
AB  - Blended water, always existing in a drinking water distribution system (DWDS)
      with different sources, can cause some unintended results, including corrosion
      and/or release of corrosion by-products. Although some studies have specially
      focused on the blended water in DWDSs, the water quality characteristics,
      variations, and mechanisms for corrosion and metal release have not been fully
      understood. This study aims to examine the characteristics and evaluate the
      corrosion potential of blended water in X city DWDS using four indices of
      Langelier saturation index (LSI), Ryznar stability index (RSI), Puckorius scaling
      index (PSI), and calcium carbonate precipitation potential (CCPP). Physical and
      chemical analysis showed that the values of pH, total dissolved solids (TDS),
      sulfate (SO42-), and chloride (Cl-) in blended water were always at acceptable
      levels, while some free residual chlorine concentrations fell outside the
      regulatory standards (>= 0.05 mg/L) with the minimum of 0.01 mg/L. Most
      parameters except pH varied in large ranges with maximum to minimum ratios (MMRs)
      over 2.25. The mean values of the LSI, RSI, PSI, and CCPP indices were - 0.44,
      8.65, 8.79, and - 1.95 mg/L CaCO3, respectively, indicating that the blended
      water was slightly corrosive. For the three zones, Z2 had the highest mean levels
      of TDS (320.84 mg/L), alkalinity (188.70 mg/L CaCO3), SO42- (13.69 mg/L), Cl-
      (36.37 mg/L), calcium hardness (Ca2+) (28.99 mg/L), and magnesium hardness (Mg2+)
      (15.22 mg/L) and the lowest mean level of dissolved oxygen (DO) (6.72 mg/L).
      Thus, the corrosion potential in Z2 was the lowest with the LSI, RSI, PSI, and
      CCPP values of - 0.17, 8.11, 8.08, and 2.87 mg/L CaCO3, respectively. During a
      year, the corrosion in blended water was more serious in winter with the LSI,
      RSI, PSI, and CCPP indices of - 0.79, 9.25, 9.37, - 7.54 mg/L CaCO3,
      respectively. The water corrosivity reached the minimum level in summer (LSI -
      0.12, RSI 8.05, PSI 8.03, and CCPP 5.22 mg/L CaCO3) owing to the decrease of DO
      concentrations and the increase of temperature and groundwater supplies with
      higher alkalinity. During rainy season, the concentrations of TDS, alkalinity,
      SO42-, Cl-, Ca2+, and Mg2+ in blended water were reduced by 41.05%, 40.48%,
      35.83%, 47.48%, 23.47%, and 55.73%, respectively, resulting in the increase of
      water corrosivity. More decreases of water parameters were recorded in Z2 (TDS,
      221.80 mg/L; alkalinity, 139.50 mg/L CaCO3; SO42-, 9.97 mg/L; Cl-, 13.74 mg/L;
      Ca2+, 7.10 mg/L; and Mg2+, 11.37 mg/L), because most groundwater from No. 5 WTP
      was pumped paretic water with more variations of water quality by rainfall.
      Moreover, it was suggested that Mg2+ should be considered in the corrosion
      indices, and the corrosion tendency of blended water could be reduced by
      adjusting the levels of pH, alkalinity, Ca2+, and Mg2+. The results of this
      research may pave the way for several opportunities to improve the management and
      corrosion prevention of blended water.

PMID- 30116902
TI  - The potato tuber content of microelements as affected by organic fertilisation
      and production system.
AB  - The objective of the work was to determine the effect of undersown catch crops,
      which were either autumn-incorporated or left on the soil surface as mulch for
      spring incorporation, on the microelement content in the tubers of potato
      cultivated in the integrated and organic production system. Field research was
      conducted at the Zawady Experimental Farm owned by Siedlce University of Natural
      Sciences and Humanities, Poland (52 degrees  03' 39" N, 22 degrees  33' 80" E).
      The following two factors were examined in the study: (i) organic fertilisation,
      control, farmyard manure, serradella, westerwolds ryegrass, serradella applied as
      mulch and westerwolds ryegrass applied as mulch and (ii) production system,
      organic and integrated. Microelements (B, Cu, Fe, Mn, Zn) were determined in
      potato tubers samples. The tubers of potato manured with autumn-incorporated
      serradella had the highest iron and zinc contents, whereas tubers following
      autumn-incorporated serradella and spring-incorporated serradella mulch had the
      highest boron content. Manuring with undersown catch crops and farmyard manure
      contributed to a decline in the potato tuber content of copper and manganese.
      Potato cultivated in the integrated production system contained more copper,
      manganese and zinc, whereas organic tubers had more iron and boron.

PMID- 30116903
TI  - Frequency and characteristics of traumatic brain injury in restrained drivers
      involved in road traffic accidents.
AB  - BACKGROUND: While seatbelt is an important device protecting drivers from
      traumatic brain injury (TBI), it has rarely been reported how often and in what
      circumstances restrained drivers sustain TBI after road traffic accident (RTA).
      Whole-body computed tomography (WBCT) for blunt trauma patients may provide a
      unique opportunity to investigate the frequency and characteristics of TBI
      sustained by restrained drivers. METHODS: A single-center, retrospective
      observational study was conducted using prospectively acquired data. Between
      January 2013 and December 2017, 409 restrained drivers (284 men/125 women, mean
      age of 45.0 +/- 19.1 years) whose vehicle had been severely damaged in RTAs
      underwent WBCT for evaluation of injuries. Multivariate regression analysis was
      performed to identify variables predictive of TBI. Influence of collision
      patterns (frontal, lateral or rollover) on the frequency and severity of TBI was
      evaluated. Relationship between collision patterns and CT findings was also
      reviewed. RESULTS: Thirty-one restrained drivers (7.6%) sustained TBI after RTA.
      The distribution of Glasgow Coma Scale (GCS) scores among the 31 drivers was 15
      in 9, 13-14 in 9, 9-12 in 4, and <= 8 in 9, indicating that the majority of TBIs
      were classifiable as mild. The frequency of TBI in alert and oriented drivers,
      i.e., those with a GCS score of 15, was 2.9%. Multivariate regression analysis
      showed that both altered mental status (OR, 4.933; 95% CI, 1.135-21.431) and loss
      of consciousness (OR, 6.492; 95% CI, 1.669-25.249) were associated with TBI. The
      frequency of TBI tended to be higher in drivers with rollover collision than
      those with frontal collision (6 vs. 13%, p = 0.07). Interhemispheric acute
      subdural hematoma and subcortical petechial hemorrhage seemed to be
      characteristic CT findings in drivers with frontal and lateral collision,
      respectively. CONCLUSIONS: The key finding of this study, i.e., that (1) TBI was
      observed in 7.6% of restrained drivers with severe vehicular damage, may provide
      useful information to neurosurgeons who take care of RTA victims. The majority of
      the TBIs were mild without need for neurosurgical intervention. While association
      may exist between type of collision and type of brain injury, further studies
      with prospective design are warranted.

PMID- 30116904
TI  - Penetrating cervical traumatic spinal cord injury due to lawn mowing: an unusual
      case report.
AB  - We present a case of a 55-year-old farmer who suddenly experienced an electric
      sensation in the left half of his body during lawn mowing. Neurological
      examination discovered neurological deficits corresponding to an incomplete
      spinal cord injury. Magnetic resonance imaging displayed an artifact in the
      cervical region. Following, a computer tomography imaging showed a metal object,
      located intramedullary, in the cervical spinal cord. The conclusion was a
      traumatic lesion from the metal object obtained during lawn mowing. The object
      was evacuated surgically. Three years postoperatively, the patient was improved.
      Caution in diagnostics following usage of heavy machinery is advised.

PMID- 30116905
TI  - Prediction of Periventricular Leukomalacia in Neonates after Cardiac Surgery
      Using Machine Learning Algorithms.
AB  - Periventricular leukomalacia (PVL) is brain injury that develops commonly in
      neonates after cardiac surgery. Earlier identification of patients who are at
      higher risk for PVL may improve clinicians' ability to optimize care for these
      challenging patients. The aim of this study was to apply machine learning
      algorithms and wavelet analysis to vital sign and laboratory data obtained from
      neonates immediately after cardiac surgery to predict PVL occurrence. We analyzed
      physiological data of patients with and without hypoplastic left heart syndrome
      (HLHS) during the first 12 h after cardiac surgery. Wavelet transform was applied
      to extract time-frequency information from the data. We ranked the extracted
      features to select the most discriminative features, and the support vector
      machine with radial basis function as a kernel was selected as the classifier.
      The classifier was optimized via three methods: (1) mutual information, (2)
      modified mutual information considering the reliability of features, and (3)
      modified mutual information with reliability index and maximizing set's mutual
      information. We assessed the accuracy of the classifier at each time point. A
      total of 71 neonates met the study criteria. The rates of PVL occurrence were 33%
      for all patients, with 41% in the HLHS group and 25% in the non-HLHS group. The F
      score results for HLHS patients and non-HLHS patients were 0.88 and 1.00,
      respectively. Using maximizing set's mutual information improved the classifier
      performance in the all patient groups from 0.69 to 0.81. The novel application of
      a modified mutual information ranking system with the reliability index in a PVL
      prediction model provided highly accurate identification. This tool is a
      promising step for improving the care of neonates who are at higher risk for
      developing PVL following cardiac surgery.

PMID- 30116906
TI  - Comparative hydrochemical analysis of the formation of the mining lakes of As
      Pontes and Meirama (Spain).
AB  - The old lignite mines of As Pontes and Meirama are located in the northwest of
      Spain, an approximate distance of 80 km between them. Both ended their extractive
      activity at the end of 2007; the respective mining pits began to be filled at the
      beginning of 2008. The filling process, enabled by the deviation of nearby
      rivers, differed between the two cases, taking approximately 4 and a half years
      to completely fill the 547-hm3 hole at As Pontes and 8 years and 2 months to fill
      the 146-hm3 hole at Meirama. In both lakes, a steady-state hydrological regime
      has been established, in which the volume of water in the filled holes remains
      constant.Despite the difference in filling time, very similar hydrochemical
      behavior would be expected for both water masses, as the geological,
      climatological, and agroforestry environment is similar at both sites and the
      maximum depth reached by the water is also the same for both (205 m).Thus, once
      the filling of both holes was completed, a comparative hydrochemical study was
      carried out on the state of the waters of both lakes, analyzing the hydrochemical
      profiles of the most representative elements and compounds of the system, as well
      as the chemical stratification generated. In this study, the hydrochemical
      results are shown. The early completion of filling in As Pontes with respect to
      Meirama provides significant information to know the future behavior of Meirama
      due to the similarity that both mine open pit present.

PMID- 30116907
TI  - IPOM: history of an acronym.
AB  - IPOM has become a common term used by hernia surgeons. It refers to the treatment
      of a ventral hernia using an intraperitoneal placed mesh and most consider it an
      acronym for Intra-Peritoneal Onlay Mesh. Since intraperitoneal placement of mesh
      has fallen out of favor with some hernia surgeons and key-opinion-leaders
      recently, this might be the correct time to write down and preserve the history
      of this intriguing acronym.

PMID- 30116908
TI  - Effects of knee flexion and extension on the tibial tuberosity-trochlear groove
      (TT-TG) distance in adolescents.
AB  - BACKGROUND: Measurement of the tibial tubercle-trochlear groove (TT-TG) distance
      is used to assess patellofemoral instability and rotation. Since patellofemoral
      instability and acute patellar dislocation are common among adolescents, it is
      important to clarify the relationship between TT-TG distance and various flexion
      and extension angles in asymptomatic children. The purpose of the present study
      was to determine how knee flexion and extension influence TT-TG-distance values
      measured using 3D imaging in an anatomic axial plane among asymptomatic
      adolescents. METHODS: We performed magnetic resonance imaging (MRI) of 26 knees
      in 13 adolescents (8 boys and 5 girls) of 11-17 years of age, with no known
      patellofemoral disorders. Imaging was performed with 3.0 T MRI with the knee at
      four separate angles of flexion between 0 degrees  and 30 degrees . Measurements
      were made by two independent blinded raters. RESULTS: The mean TT-TG distance in
      millimetres was 11.1-0.29 * the angle in degrees. TT-TG distance decreased with
      greater flexion, showing a mean decrease of 0.29 mm (SD, 0.04) per degree of
      increased flexion (p < 0.001). We found significant inter-observer (Pearson's r =
      0.636, p = 0.03) and intra-observer (Pearson's r = 0.792, p <= 0.001)
      correlations. TT-TG values were not significantly correlated with age, length,
      weight, or body mass index. The rate of TT-TG change (change between consecutive
      TT-TG values/change between consecutive angles) was significantly negatively
      correlated with length (p = 0.014), weight (p = 0.004), and body mass index (p =
      0.025). CONCLUSIONS: Our data revealed that TT-TG distance assessed in the
      anatomic axial plane decreased with greater flexion in adolescent. Moreover, this
      effect of knee angle was stronger in smaller subjects. These findings support the
      need for a standardized protocol for TT-TG distance measurement in adolescents.

PMID- 30116911
TI  - Glucose Targets and Insulin Choice in Pregnancy: What Has Changed in the Last
      Decade?
AB  - PURPOSE OF REVIEW: To review current glycaemic targets and the potential use of
      newer insulin formulations in pregnancy. RECENT FINDINGS: The impact of stricter
      glycaemic control on perinatal outcomes remains controversial, showing
      conflicting results. Current ongoing randomised trials investigating the role of
      tighter glucose targets in pregnancy should help clarify the benefit of tighter
      glucose control. Optimal timing for self-monitoring blood glucose (SMBG) remains
      debatable. Data suggest that post-prandial SMBG, particularly at 1 h, offers the
      best prediction of adverse perinatal outcome. To achieve these targets, insulin
      is the standard therapy. Novel insulin formulations offer benefits outside of
      pregnancy. Recent data on the use of new insulins in pregnancy (e.g. insulin
      degludec and glargine (U 300)) is limited to case reports. Glycaemic targets have
      remained unchanged in the last decade. Studies using stricter glycaemic targets
      may improve perinatal outcomes. Newer insulin formulations may offer increased
      flexibility and glycaemic control. Clinicians caring for women with diabetes
      striving to minimise adverse perinatal outcomes will find this review of
      interest.

PMID- 30116910
TI  - Impact of rifampicin-inhibitable transport on the liver distribution and tissue
      kinetics of erlotinib assessed with PET imaging in rats.
AB  - BACKGROUND: Erlotinib is an epidermal growth factor receptor (EGFR)-targeting
      tyrosine kinase inhibitor approved for treatment of non-small cell lung cancer.
      The wide inter-individual pharmacokinetic (PK) variability of erlotinib may
      impact treatment outcome and/or toxicity. Recent in vivo studies reported a
      nonlinear uptake transport of erlotinib into the liver, suggesting carrier
      mediated system(s) to mediate its hepatobiliary clearance. Erlotinib has been
      identified in vitro as a substrate of organic anion-transporting polypeptide
      (OATP) transporters which expression does not restrict to hepatocytes and may
      impact the tissue uptake of erlotinib in vivo. RESULTS: The impact of rifampicin
      (40 mg/kg), a potent OATP inhibitor, on the liver uptake and exposure to tissues
      of 11C-erlotinib was investigated in rats (4 animals per group) using positron
      emission tomography (PET) imaging. Tissue pharmacokinetics (PK) and corresponding
      exposure (area under the curve, AUC) were assessed in the liver, kidney cortex,
      abdominal aorta (blood pool) and the lungs. The plasma PK of parent 11C-erlotinib
      was also measured using arterial blood sampling to estimate the transfer rate
      constant (kuptake) of 11C-erlotinib from plasma into different tissues. PET
      images unveiled the predominant distribution of 11C-erlotinib-associated
      radioactivity to the liver, which gradually moved to the intestine, thus
      highlighting hepatobiliary clearance. 11C-erlotinib also accumulated in the
      kidney cortex. Rifampicin did not impact AUCaorta but reduced kuptake, liver (p <
      0.001), causing a significant 27.3% decrease in liver exposure (p < 0.001).
      Moreover, a significant decrease in kuptake, kidney with a concomitant decrease
      in AUCkidney (- 30.4%, p < 0.001) were observed. Rifampicin neither affected
      kuptake, lung nor AUClung. CONCLUSIONS: Our results suggest that 11C-erlotinib is
      an in vivo substrate of rOATP transporters expressed in the liver and possibly of
      rifampicin-inhibitable transporter(s) in the kidneys. Decreased 11C-erlotinib
      uptake by elimination organs did not translate into changes in systemic exposure
      and exposure to the lungs, which are a target tissue for erlotinib therapy.

PMID- 30116909
TI  - Imaging for Screening and Surveillance of Patients with Hereditary Forms of Renal
      Cell Carcinoma.
AB  - PURPOSE OF REVIEW: To summarize the literature providing the basic genetic and
      clinical characteristics of renal cell carcinoma (RCC) familial syndromes, as
      well as to describe associated unique imaging characteristics and appropriate
      imaging protocols. RECENT FINDINGS: At least 5-8% of RCC cases are associated
      with hereditary syndromes. These patients are prone to developing multiple renal
      tumors or associated malignancies and require more intense diagnostic and follow
      up imaging studies. New familial types of RCC are continuously discovered, vis-a
      vis recent characterization of BAP1 associated RCC and MITF associated cancer
      syndrome. With increasing number of recognizable familial syndromes associated
      with RCC, physicians should be familiar with the different syndromes, the
      associated risks of malignancy and appropriate imaging protocols.

PMID- 30116912
TI  - Sorafenib in patients with progressed and refractory bone tumors.
AB  - Patients with metastatic, progressive, or recurrent bone tumors have a dismal
      outcome. Sorafenib has been proposed as an effective salvage regimen for some
      malignancies. Thus, we sought to evaluate this approach for young patients with
      relapsed or refractory bone tumors. Twelve patients with refractory bone tumors
      (two with Ewing sarcoma, two with chondrosarcoma, and eight with osteosarcoma)
      received salvage treatment with sorafenib. All patients had standard tumor
      imaging and laboratory evaluation. All toxicities were documented. At the time of
      the beginning of sorafenib treatment median age among 12 patients was 18 years
      (range 4.1-27.9 years), eight were male, and eight had osteosarcoma. All received
      sorafenib because of relapse. Seven patients were treated parallel to other
      standard chemotherapy. Overall response rate was 75%. Median time to sorafenib
      time to progression for patients with osteosarcoma was 4 months (range 1.8-7.9
      months). Four patients (33%) are alive, in that two with no evidence of disease
      with a median follow-up of 41 months (range 26.5-60.9 months). The estimated 5
      year overall survival (OS) for the whole group was 64.49%. There were no serious
      toxicities. Sorafenib is well-tolerated in young patients with bone tumors, and
      particularly could be an option for patients with metastatic disease and
      refractory osteosarcoma. Sorafenib only allows to extend OS and different
      procedures are needed to achieve permanent remission. This regimen deserves
      further investigation in the upfront management of patients with high-risk bone
      tumors.

PMID- 30116913
TI  - The Neuralgias.
AB  - PURPOSE OF REVIEW: Neuralgias are characterized by pain in the distribution of a
      cranial or cervical nerve. Typically, they are brief, paroxysmal, painful
      attacks, although continuous neuropathic pain may occur. The most commonly
      encountered conditions are trigeminal, postherpetic, and occipital neuralgia.
      Less common neuralgias include glossopharyngeal, superior laryngeal,
      auriculotemporal, and nervus intermedius neuralgia, among others. The approach to
      diagnosis and treatment of this group of disorders is reviewed. RECENT FINDINGS:
      Recent guidelines of medication administration, the use of botulinum toxin, and
      more targeted procedures have improved treatment of neuralgias. Patients who
      present with neuralgias should have imaging studies to investigate for structural
      abnormalities unless the etiology is apparent. Management of both common and rare
      neuralgias can be challenging and is best guided by the most recent available
      evidence.

PMID- 30116915
TI  - Polyaniline/palladium nanohybrids for moisture and hydrogen detection.
AB  - Palladium nanoparticles display fascinating electronic, optical and catalytic
      properties, thus they can be used for various applications such as sensor
      fabrication. Conducting polymers such as polyaniline have also been widely used
      in sensor technology due to its cost effectiveness, versatility, and ease of
      synthesis. In this research, attention was given to unify the exceptional
      properties of these two materials and construct palladium nanoparticle coated
      polyaniline films to detect hydrogen and moisture. Electrochemical polymerization
      of aniline was carried out on gold sputtered epoxy resin boards. Polyaniline film
      was generated across a gap of 0.2 mm created by a scratch made on the gold
      coating prior to electrochemical polymerization. A palladium nanoparticle
      dispersion was prepared using sonochemical reduction method and coated on to
      polyaniline film using drop-drying technique. Polyaniline only films were also
      fabricated for comparative analysis. Sensitivity of films towards humidity and
      hydrogen was evaluated using impedance spectroscopy in the presence of the
      respective species. According to the results, polyaniline films exhibited an
      impedance drop in the presence of humidity and the response was significantly
      improved once palladium nanoparticles were incorporated. Interestingly,
      polyaniline only films did not respond to hydrogen. Nevertheless, palladium
      nanoparticle coated polyaniline films exhibited remarkable response towards
      hydrogen.

PMID- 30116914
TI  - Psychological distress, neuroticism and disability associated with secondary
      chronic headache in the general population - the Akershus study of chronic
      headache.
AB  - BACKGROUND: Primary headaches are associated with psychological distress,
      neuroticism and disability. However, little is known about headache-related
      disability and psychological distress among people with secondary chronic
      headaches. METHODS: 30,000 persons aged 30-44 from the general population was
      screened for headache by a questionnaire. The responder rate was 71%. The
      International Classification of Headache Disorders with supplementary definitions
      for chronic rhinosinusitis and cervicogenic headache were used. The Hopkins
      Symptom Checklist-25 assessed high psychological distress, the Migraine
      Disability Assessment questionnaire assessed disability, and Eysenck Personality
      Questionnaire assessed neuroticism. RESULTS: Ninety-five of the 113 eligible
      participants (84%) completed the self-reported questionnaire. A total of 38
      people had chronic post-traumatic headache, 21 had cervicogenic headache, and 39
      had headache attributed to chronic rhinosinusitis, while 9 had co-occurrence of
      chronic post-traumatic and cervicogenic headache. Six persons had miscellaneous
      secondary chronic headaches. Overall, 49% of those with secondary chronic
      headache reported high psychological distress, which is significantly higher than
      in the general population. A high level of neuroticism was significantly more
      common in those with secondary chronic headache than in the general population.
      Severe headache-related disability was reported by 69%. 92 persons were followed
      up after 3 years. A low headache frequency was the only significant predictor of
      improvement of >= 25% in headache days. Having post-traumatic or cervicogenic
      headache and not headache attributed to chronic rhinosinusitis predicted an
      increased risk > 25% worsening of headache days or having a severe disability at
      3 years follow-up. CONCLUSION: Psychological distress and neuroticism were more
      common among people with secondary chronic headache than in the general
      population. Only a high headache frequency was significantly associated with
      increased headache disability at baseline and a poor prognosis in the long term.

PMID- 30116916
TI  - Reduced HBV cccDNA and HBsAg in HBV-associated hepatocellular carcinoma tissues.
AB  - Approximately 50% of hepatocellular carcinoma (HCC) is attributable to chronic
      infection with hepatitis B virus (HBV). Serum hepatitis B surface antigen (HBsAg)
      is an important diagnostic marker of HBV infection, whereas intrahepatic HBV
      covalently closed circular DNA (cccDNA) is a surrogate marker of HBV persistence.
      This study aimed to investigate relationships between serum HBsAg, intrahepatic
      HBsAg, and intrahepatic cccDNA in HBV-associated HCC. Intrahepatic HBsAg was
      determined by immunohistochemistry in matched non-cancerous and HCC tissues from
      88 patients; 56 patients (63.64%) were serum HBsAg positive. In serum HBsAg
      positive group, intrahepatic HBsAg was positive staining in 73.2% of non
      cancerous tissues, but only in 10.7% of HCC tissues. Significant correlation
      between serum HBsAg and intrahepatic HBsAg was observed in non-cancerous tissues
      (p < 0.001), but not in HCC tissues (p = 0.415). Absolute quantification of
      intrahepatic cccDNA was performed by droplet digital PCR in tissues from 30
      patients; 18 patients (60%) were serum HBsAg positive. In serum HBsAg-positive
      group, intrahepatic cccDNA was detected in 66.66% of non-cancerous tissues, but
      only in 5.55% of HCC tissue; intrahepatic cccDNA levels in non-cancerous tissues
      were significantly higher than those in HCC tissues (p < 0.001), and correlated
      with serum HBsAg (p < 0.01). Significant correlations between intrahepatic HBsAg
      and intrahepatic cccDNA were found in both non-cancerous tissues (p < 0.01) and
      HCC tissues (p < 0.05). We concluded that HBV cccDNA and intrahepatic HBsAg in
      HBV-associated HCC tissues were significantly reduced, as compared with matched
      non-cancerous tissues. This warrants further investigation into the impacts and
      the cause(s) of cccDNA reduction in HBV-associated HCC tissues, which might yield
      novel immune-related therapy for HBV-associated HCC.

PMID- 30116918
TI  - Mathematical deep learning for pose and binding affinity prediction and ranking
      in D3R Grand Challenges.
AB  - Advanced mathematics, such as multiscale weighted colored subgraph and element
      specific persistent homology, and machine learning including deep neural networks
      were integrated to construct mathematical deep learning models for pose and
      binding affinity prediction and ranking in the last two D3R Grand Challenges in
      computer-aided drug design and discovery. D3R Grand Challenge 2 focused on the
      pose prediction, binding affinity ranking and free energy prediction for
      Farnesoid X receptor ligands. Our models obtained the top place in absolute free
      energy prediction for free energy set 1 in stage 2. The latest competition, D3R
      Grand Challenge 3 (GC3), is considered as the most difficult challenge so far. It
      has five subchallenges involving Cathepsin S and five other kinase targets,
      namely VEGFR2, JAK2, p38-alpha, TIE2, and ABL1. There is a total of 26 official
      competitive tasks for GC3. Our predictions were ranked 1st in 10 out of these 26
      tasks.

PMID- 30116917
TI  - ECMO and Short-term Support for Cardiogenic Shock in Heart Failure.
AB  - PURPOSE OF REVIEW: This review aims to discuss the role of ECMO in the treatment
      of cardiogenic shock in heart failure. RECENT FINDINGS: Trials done previously
      have shown that IABP does not improve survival in cardiogenic shock compared to
      medical treatment, and that neither Impella 2.5 nor TandemHeart improves survival
      compared to IABP. The "IMPRESS in severe shock" trial compared Impella CP with
      IABP and found no difference in survival. A meta-analysis of cohort studies
      comparing ECMO with IABP showed 33% improved 30-day survival with ECMO (risk
      difference 33%; 95% CI 14-52%; p = 0.0008; NNT 3). ECMO is indicated in medically
      refractory cardiogenic shock. ECMO can be considered in cardiogenic shock
      patients with estimated mortality of more than 50%. ECMO is probably the MCS of
      choice in cardiogenic shock with; biventricular failure, respiratory failure,
      life-threatening arrhythmias and cardiac arrest.

PMID- 30116919
TI  - Screening of a beta-cypermethrin-degrading bacterial strain Brevibacillus
      parabrevis BCP-09 and its biochemical degradation pathway.
AB  - A novel beta-cypermethrin (Beta-CP)-degrading strain isolated from activated
      sludge was identified as Brevibacillus parabrevis BCP-09 based on its
      morphological and physio-biochemical characteristics, and 16S rRNA gene analysis.
      Strain BCP-09 could effectively degrade Beta-CP at pH 5.0-9.0, 20-40  degrees C,
      and 10-500 mg L-1 Beta-CP. Under optimal conditions (pH 7.41, 38.9  degrees C,
      30.9 mg L-1 Beta-CP), 75.87% Beta-CP was degraded within 3 days. Beta-CP
      degradation (half-life, 33.45 h) and strain BCP-09 growth were respectively
      described using first-order-kinetic and logistic-kinetic models. Seven
      metabolites were detected by high-performance liquid chromatography and gas
      chromatography-mass spectrometry- methyl salicylate, catechol, phthalic acid,
      salicylic acid, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid, 3
      phenoxybenzaldehyde, and 3-phenoxybenzoic acid (3-PBA). The major Beta-CP
      metabolite, 3-PBA was further degraded into phenol, benzoic acid, and 4
      methylhexanoic acid. BCP-09 also degraded aromatic compounds such as phenol,
      catechol, and protocatechuic acid. Beta-CP appears to be mainly degraded into 3
      PBA, which is continuously degraded into smaller benzene or chain compounds.
      Thus, strain BCP-09 could form a complete degradation system for Beta-CP and
      might be considered a promising strain for application in the bioremediation of
      environments and agricultural products polluted by Beta-CP.

PMID- 30116921
TI  - Evolutionary justifications for human reproductive limitations.
AB  - Common human reproductive inefficiencies have multiple etiologies. Going against
      chance, many effects, such as polycystic ovaries, endometriosis, and folate
      metabolic issues, have genetic components, while aneuploid losses arise from
      diverse mitotic and meiotic errors at different stages, some transitory. This can
      be advantageous, since greater overall survival with fewer offspring can increase
      reproductive success. Benefits primarily accrue to mothers, who bear most child
      related costs, and for whom early losses are less costly than late. Different
      adaptations to different situations reflect human evolutionary history. For early
      speciation, periodic climate extremes repeatedly reduced resources, favoring
      limitations while contracted populations helped fix relevant genes. Later, under
      better conditions, evolving social cooperation could increase fecundity faster
      than it added resources, further supporting reproductive suppression through
      mitotic aneuploidy, with very early losses minimizing maternal costs. The
      grandmother hypothesis suggests benefits in limiting reproduction as maternal age
      increased pregnancy risks in order to support grandchildren as they arrived,
      selecting for maternal age-related meiotic aneuploidy. Finally, with variable
      short-term agricultural shortages, acute reproductive responses arose through
      chromatin "nutrient sensor"-regulated epigenetic effects that also shifted some
      lethal effects earlier, reducing both maternal and mutation load costs. Overall,
      despite suggestions to the contrary, it is likely that human selective pressures
      have not decreased with civilization, but that many of the costs have been
      shifted to early reproduction.

PMID- 30116920
TI  - Membrane potential and delta pH dependency of reverse electron transport
      associated hydrogen peroxide production in brain and heart mitochondria.
AB  - Succinate-driven reverse electron transport (RET) is one of the main sources of
      mitochondrial reactive oxygen species (mtROS) in ischemia-reperfusion injury. RET
      is dependent on mitochondrial membrane potential (Deltapsim) and transmembrane pH
      difference (DeltapH), components of the proton motive force (pmf); a decrease in
      Deltapsim and/or DeltapH inhibits RET. In this study we aimed to determine which
      component of the pmf displays the more dominant effect on RET-provoked ROS
      generation in isolated guinea pig brain and heart mitochondria respiring on
      succinate or alpha-glycerophosphate (alpha-GP). Deltapsim was detected via
      safranin fluorescence and a TPP+ electrode, the rate of H2O2 formation was
      measured by Amplex UltraRed, the intramitochondrial pH (pHin) was assessed via
      BCECF fluorescence. Ionophores were used to dissect the effects of the two
      components of pmf. The K+/H+ exchanger, nigericin lowered pHin and DeltapH,
      followed by a compensatory increase in Deltapsim that led to an augmented H2O2
      production. Valinomycin, a K+ ionophore, at low [K+] increased DeltapH and pHin,
      decreased Deltapsim, which resulted in a decline in H2O2 formation. It was
      concluded that Deltapsim is dominant over ?pH in modulating the succinate- and
      alpha-GP-evoked RET. The elevation of extramitochondrial pH was accompanied by an
      enhanced H2O2 release and a decreased ?pH. This phenomenon reveals that from the
      pH component not ?pH, but rather absolute value of pH has higher impact on the
      rate of mtROS formation. Minor decrease of Deltapsim might be applied as a
      therapeutic strategy to attenuate RET-driven ROS generation in ischemia
      reperfusion injury.

PMID- 30116922
TI  - Do patients who achieve pregnancy using IVF-PGS do the recommended genetic
      diagnostic testing in pregnancy?
AB  - PURPOSE: Patients undergoing in-vitro fertilization (IVF) with preimplantation
      genetic screening (PGS) are counseled about the limitations of this technique. As
      part of the consent process for PGS, physicians recommend diagnostic genetic
      testing performed in early pregnancy to definitively rule out chromosomal
      abnormalities. We have noted anecdotally, however, that few patients undergo the
      recommended diagnostic testing. In this study, we are examining if women who
      conceived using IVF-PGS did early pregnancy chromosomal testing, and if they did,
      what type of testing they had. METHODS: This study was performed from 2015 to
      2017 in the Division of Reproductive Endocrinology and Infertility at
      Northwestern University. We included patients who became pregnant after IVF-PGS
      who were seen by the Division of Reproductive Genetics and non-PGS control group.
      RESULTS: Sixty-eight patients were included. A total of 50 patients (73.5%) opted
      for non-invasive prenatal screening; 5 (7.4%) had invasive testing (4 had
      chorionic villus sampling and 1 had amniocentesis). A total of 13 patients (19%)
      declined further genetic testing. When comparing demographic data, the mean age
      was significantly higher in the group of patients who pursued non-invasive
      testing than in the group who declined further testing (37.15 vs 34.05 years old,
      p < 0.05). Control group declined invasive diagnostic testing. CONCLUSIONS: Most
      patients who conceive using IVF-PGS do not pursue diagnostic prenatal chromosomal
      testing. Future studies focusing on decision making in this patient group are
      warranted to further elucidate why a small percentage of patients opt for
      diagnostic testing, even when adequately counseled about the inherent limitations
      of PGS.

PMID- 30116923
TI  - First molecular detection of Anaplasma phagocytophilum in the hard tick
      Rhipicephalus haemaphysaloides in Taiwan.
AB  - Anaplasma phagocytophilum is transmitted mainly by hard ticks and can cause
      potentially fatal granulocytic anaplasmosis in humans, but its occurrence in
      ticks in Taiwan has never been investigated although this pathogen has been
      detected in Taiwanese rodents before. Ticks collected from small mammals in
      Hualien, eastern Taiwan, were assayed for Anaplasma infections; infections of
      Rickettsia and Apicomplexa protozoans were also studied. Of the 270 individually
      assayed Rhipicephalus haemaphysaloides ticks, A. phagocytophilum was identified
      in a nymphal tick. Parasites most similar to Anaplasma bovis, Rickettsia
      rickettsii, Rickettsia sp. TwKM01, and at least seven apicomplexan species
      (including genera Cryptosporidium, Hepatozoon, and Theileria) were also
      identified. This study shows that A. phagocytophilum does occur in the hard tick
      in Taiwan, although whether R. haemaphysaloides can vector this pathogen remains
      to be determined. This work also reveals a high diversity of tick-borne bacteria
      and protozoans circulating in a small region and calls for further research on
      their potential risks for human health.

PMID- 30116924
TI  - Response of the predatory mite Cydnoseius negevi (Acari: Phytoseiidae) to webbing
      of the date palm mite, Oligonychus afrasiaticus (Acari: Tetranychidae), on date
      palm fruits and leaves.
AB  - The behavioral response of a generalist phytoseiid predator, Cydnoseius negevi
      (Swirskii & Amitai) (Acari: Phytoseiidae) to the complicated webbing of the date
      palm mite (DPM) Oligonychus afrasiaticus (McGregor) (Acari: Tetranychidae) was
      evaluated for the first time on date palm leaves and fruits, both in the
      laboratory and on field-collected samples. Cydnoseius negevi used its first pair
      of legs in a swimming-like to-and-fro movement to penetrate the complicated
      webbing of DPM and demonstrated three attack behaviors, i.e., patrolling (PG),
      web invasion (WI), and web penetration (WP), against the webbing of DPM on date
      fruits and leaves. The time spent by the predator on attack behaviors was
      significantly longer in the laboratory for treatments where either more prey
      females or immature stages along with females were present. The time spent by C.
      negevi on response behaviors such as searching, grooming, and resting increased
      with increased number of DPM females and with the addition of immature stages
      along with DPM females. Cydnoseius negevi, even though being a generalist
      phytoseiid predator, showed its potential towards penetrating the complex dense
      webs of DPM on date palm fruits and leaves. If released in suitable numbers prior
      to establishment of DPM colonies, C. negevi may prove to be an effective
      biological control agent.

PMID- 30116925
TI  - Seasonal characteristics of chemical compositions and sources identification of
      PM2.5 in Zhuhai, China.
AB  - Fine particulate matter is associated with adverse health effects, but exactly
      which characteristics of PM2.5 are responsible for this is still widely debated.
      We evaluated seasonal dynamics of the composition and chemical characteristics of
      PM2.5 in Zhuhai, China. PM2.5 characteristics at five selected sites within
      Zhuhai city were analyzed. Sampling began on January 10, 2015, and was conducted
      for 1 year. The ambient mass concentration, carbon content (organic and elemental
      carbon, OC and EC), level of inorganic ions, and major chemical composition of
      PM2.5 were also determined. Average concentrations of PM2.5 were lower than the
      National Ambient Air Quality Standard (NAAQS) 24-h average of 65 MUg/m3. The
      daily PM2.5 concentration in Zhuhai city exhibited clear seasonal dynamics, with
      higher daily PM2.5 concentrations in autumn and winter than in spring and summer.
      Carbon species (OC and EC) and water-soluble ions were the primary components of
      the PM2.5 fraction of particles. Apart from OC and EC, chemical species in PM2.5
      were mainly composed of NH4+ and SO42-. There was a marked difference between the
      summer and winter periods: the concentrations of OC and EC in winter were roughly
      3.4 and 4.0 times than those in summer, while NH4+, SO42-, NO3-, and Na+ were
      3.2, 4.5, 28.0, and 5.7 times higher in winter than those in summer,
      respectively. The results of chemical analysis were consistent with three sources
      dominating PM2.5: coal combustion, biomass burning, and vehicle exhaust; road
      dust and construction; and from reaction of HCl and HNO3 with NH3 to form NH4Cl
      and NH4NO3. However, additional work is needed to improve the mass balance and to
      obtain the source profiles necessary to use these data for source apportionment.

PMID- 30116927
TI  - Dysregulated Pornography Use and the Possibility of a Unipathway Approach.

PMID- 30116926
TI  - Left atrial mechanics in children: insights from new applications of strain
      imaging.
AB  - Our principal aim was to describe functional changes in dilated left atrium (LA)
      of children by using new applications of LA strain. We studied 66 patients (age
      range 0.2-22 years) consisting of 33 with LA enlargement. We utilized speckle
      tracking imaging for assessment LA longitudinal strain (S) and longitudinal
      displacement (D). S-D loops were generated by plotting S and D data along Y and X
      axes, respectively. We also measured noninvasive LA stiffness index, [Formula:
      see text] (%-1). Peak S in controls was 51.16 +/- 19.45% versus 23.16 +/- 13.66%
      in dilated LA (p < 0.0001). S-D loops in dilated LA group were significantly
      smaller compared to controls (2.62 +/- 2.88 units vs. 5.24 +/- 4.00 units, p <
      0.01). Noninvasive LA stiffness index was higher in dilated LA group (0.77 +/-
      0.63%-1 vs. 0.17 +/- 0.07%-1, p < 0.0001). A cut-off LA stiffness value of 0.25%
      1 was found to maximize sensitivity and specificity (84.0% and 84.85%,
      respectively). Children with enlarged LA demonstrate decreased peak S, abnormal S
      D loops and increased LA stiffness, providing a newer insight into LA function.
      Evaluation of LA mechanics may be applied in future as a surrogate for left
      ventricular filling parameters.

PMID- 30116928
TI  - Self-Perceived Problematic Pornography Use: Beyond Individual Differences and
      Religiosity.

PMID- 30116929
TI  - Power Affects Sexual Assertiveness and Sexual Esteem Equally in Women and Men.
AB  - Common stereotypes hold that men and women differ strongly in their attitudes
      toward sex and that such differences are amplified by social power. In contrast,
      an emerging literature suggests that social power affects both sexes similarly,
      thus potentially attenuating differences between the sexes. Four samples obtained
      in the Netherlands, the U.S., Britain, and South-East Asia (total N = 1985) test
      the effect of social power (operationalized as self-reported amount of power over
      others at the work place) on validated self-report measures of sexual
      assertiveness and sexual esteem. Across all samples, power was associated with
      greater sexual assertiveness and sexual esteem-equally for men and women.
      Furthermore, effects of power were larger and more consistent than differences
      between men and women. These findings add to an emerging literature, suggesting
      that often-observed differences between male and female sexuality actually
      reflect power differences. This suggests that such differences decrease with
      greater social equality.

PMID- 30116930
TI  - Instrument usage in laparoscopic gynecologic surgery: a prospective clinical
      trial.
AB  - PURPOSE: To evaluate instrumental usage in laparoscopic gynecological surgeries
      and to develop key timesets of a laparoscopic operation, which allows
      categorization of the operation time into different sections. METHODS: In this
      prospective clinical observational study, frequency of instrument usage, time for
      instrument switches, and instrument utilization time were recorded in a
      standardized manner for laparoscopic surgeries in 103 endoscopic surgeries.
      RESULTS: A standard equipment (including atraumatic grasping forceps, irrigation
      and suction device, bipolar clamp, and laparoscopic scissors) was used for nearly
      all interventions. Bipolar clamps and scissors were changed most frequently. The
      tool used for the longest amount of time was the atraumatic grasping forceps.
      Laparoscopic instruments were switched 51 times per surgery (range 2-250 times).
      One instrument switch lasted for a median of 0.13 min (0.08-1.2 min). Median time
      for instrument switch for a single surgery added up to 6.83 min. Instrument
      switches required 10.5% of the overall operation time. CONCLUSION: We analyzed
      the current instrument usage in laparoscopic gynecological surgeries. The results
      of our standardized investigation suggest ways to reduce the time required for
      surgery and provide starting points for the standardization of the work routine.

PMID- 30116931
TI  - Recurrent pregnancy loss and future risk of female malignancies.
AB  - PURPOSE: To investigate whether patients with a history of recurrent pregnancy
      loss (RPL) have an increased risk for future female malignancies. METHODS: A
      retrospective population-based study compared the incidence of long-term female
      malignancies in a cohort of women with and without a history of RPL (2 or more
      consecutive pregnancy losses). Deliveries occurred between the years 1988 and
      2013, with a mean follow-up duration of 12 years. Women with known malignancies
      before the index pregnancy were excluded from the analysis. Female malignancies
      were divided according to specific type including ovary, breast, uterine and
      uterine cervix. Kaplan-Meier survival curve was used to estimate the cumulative
      incidence of malignancies. Cox proportional hazards model was used to determine
      the adjusted hazard ratios (HR) for female malignancy after controlling for
      confounders. RESULTS: During the study period, 106,265 patients met the inclusion
      criteria; 6.6% (n = 7052) of patients had a diagnosis of RPL. During the follow
      up period, patients with RPL had a significantly increased risk of being
      diagnosed with female malignancies as a group, while individually there was an
      increased risk of breast and uterine cervix cancer. Using a Kaplan-Meier survival
      curve, patients with a history of RPL had a significantly higher cumulative
      incidence of female malignancies. Using a Cox proportional hazards model,
      adjusted for confounders such as smoking, parity, and diabetes mellitus, a
      history of RPL remained independently associated with female malignancies
      (adjusted HR 1.4; P = 0.003). CONCLUSIONS: RPL is independently associated with
      long-term female malignancies. Patients with a history of RPL may benefit from
      counseling and screening for breast and uterine cervix cancer in particular.

PMID- 30116932
TI  - Adverse effect of paternal hepatitis B virus infection on clinical pregnancy
      after frozen-thawed embryo transfer.
AB  - PURPOSE: This study aimed to determine the effect of paternal hepatitis B virus
      (HBV) infection on reproductive outcomes of couples undergoing frozen-thawed
      embryo transfer (FET). METHODS: This retrospective cohort study included FET
      cycles performed between January 2014 and March 2017 in couples with a hepatitis
      B surface antigen (HBsAg)-positive male partner and an HBsAg-negative female
      partner, which was categorized as HBsAg group. The FET cycles underwent by
      couples with both HBsAg-negative partners were randomly selected as controls. The
      primary outcome was clinical pregnancy. RESULTS: A total of 117 FET cycles,
      comprising 39 in the HBsAg group and 78 in the control group, were included.
      Couples with HBsAg-positive male partners had significantly lower clinical
      pregnancy rate (17.9 vs 41.0%, P = 0.013), lower implantation rate (11.1 vs
      24.5%, P = 0.014), and lower live birth rate (12.8 vs 30.8%, P = 0.034) compared
      with the control group. Moreover, the multivariate logistic regression analysis
      showed that paternal HBV infection was negatively associated with clinical
      pregnancy (odds ratio = 0.297, 95% confidence interval 0.108-0.817, P = 0.019).
      The miscarriage rate was not significantly different between the two groups (28.6
      vs 25.0%, P = 1.000). CONCLUSIONS: Paternal HBV infection resulted in a lower
      frequency of clinical pregnancy after FET, a difference that was probably
      attributed to a detrimental effect of HBV on the ability of embryos to survive
      freezing and thawing.

PMID- 30116933
TI  - Arctiin Prevents LPS-Induced Acute Lung Injury via Inhibition of PI3K/AKT
      Signaling Pathway in Mice.
AB  - Arctiin is a lignin isolated from Arctium lappa which has been known to have anti
      viral and anti-inflammatory effects. The aim of this study is to explore the
      protective effect of arctiin on lipopolysaccharide (LPS)-induced inflammatory
      responses in acute lung injury (ALI) model of mice. Male BALB/c mice were
      pretreated with commercial arctiin (10, 20, and 40 mg/kg) 1 h prior to LPS
      challenge. Twelve hours later, airway inflammation was assessed. We assessed the
      effects of arctiin on the LPS-induced production of TNF-alpha, IL-6, and IL-1beta
      in the bronchoalveolar lavage fluid (BALF). The lung wet-to-dry weight ratio,
      myeloperoxidase (MPO) activity, and inflammatory signaling pathway were also
      detected. Our results showed that arctiin not only significantly ameliorated LPS
      stimulated lung histopathological changes but also reduced the lung MPO activity.
      Arctiin also dramatically decreased the production of TNF-alpha, IL-1beta, and IL
      6 in the BALF. In addition, arctiin significantly inhibited LPS-induced PI3K/Akt
      phosphorylation as well as NF-kappaB activation. In conclusion, our results
      suggested that arctiin protected against LPS-induced ALI through inhibiting
      PI3K/AKT/NF-kappaB signaling pathway.

PMID- 30116934
TI  - Development of a bioclimatic wind rose tool for assessment of comfort wind
      resources in Sydney, Australia for 2013 and 2030.
AB  - This study assessed the effect of wind on human thermal comfort by preforming
      outdoor urban climatic comfort simulations using state-of-the-art heat-balance
      models of human thermo-physiology (Universal Thermal Climate Index-UTCI). A
      series of simulations for computing "wind cooling potential" have been performed
      using the UTCI index temperatures. The comfort cooling effect of wind has been
      estimated by modelling with wind taken into account, and under calm wind (0.05
      m/s) (DeltaUTCI). A novel wind rose biometeorological data visualisation tool
      that integrates an additional thermal comfort dimension into the conventional
      climatology wind rose visualisation was developed in this study. The new wind
      rose graphic tool identifies "predominant" wind directions, and whether or not
      they are "desirable" from the human thermal comfort point of view. This tool's
      utility lies in its identification of the optimal building orientation in its
      surrounding urban morphology, based on the cooling potential of wind resources
      when enhanced ventilation is desirable for thermal comfort.

PMID- 30116935
TI  - Heat loss efficiency and HSPs gene expression of Nellore cows in tropical climate
      conditions.
AB  - Adaptation is a relevant characteristic to be understood in livestock animals in
      order to maintain and raise productivity. In Brazil, the Nellore beef cattle are
      widely disseminated and well-adapted breed that present good thermoregulatory
      characteristics for tropical environment conditions. Conversely, the
      physiological and cellular mechanisms required for thermoregulation and
      thermotolerance in this breed are still limited. The aim of this study was to
      comprehend the heat loss efficiency at the whole animal level and heat shock
      response at the cellular level of Nellore cows in tropical climate conditions.
      Healthy purebred Nellore cows were classified according to their capacity to lose
      body heat as Efficient or Inefficient based on vaginal temperature which was
      continuously monitored by data-loggers. Rectal, tail, and ocular temperatures,
      sweating rate, and respiratory frequency were collected to assess other
      thermoregulatory responses. Peripheral mononuclear cells were used for gene
      expression of heat shock proteins 60, 70, and 90 induced by in vitro heat
      treatments at 38, 40, and 42  degrees C. In our findings, the Efficient cows
      presented higher sweating rates compared to Inefficient cows that presented
      higher rectal temperature with greater amplitude of vaginal temperature profile.
      Transcription of the HSP genes was stable at 38 and 40  degrees C and decreased
      for all HSP genes at 42  degrees C. In conclusion, the Nellore efficiency to lose
      heat was mainly associated with their sweating capacity and cellular
      thermotolerance confirmed by the maintenance of heat shock proteins transcripts
      under heat stress. Taken together, this knowledge contributes as a future key for
      genetic selection of adapted animals.

PMID- 30116937
TI  - How to reduce osteopenia in total knee arthroplasty?
AB  - BACKGROUND: Osteopenia of the front half of the distal femur is a well-known
      problem after total knee arthroplasty (TKA) with secondary issues after years,
      especially when must be addressed fractures or revisions for loosening. Stress
      shielding has been recognized as a cause in different biomechanical studies of
      the bone. QUESTION/PURPOSES: It was logical to look for a solution by changing
      the design to minimize stress shielding behind the femoral shield. PATIENTS AND
      METHODS: It was proved that radiological measure of bone density was reliable
      although not so early and accurate as densitometry. We used a shield without
      posterior fixation of the trochlea in a series of 21 TKA with radiological
      measures, preoperative, at 3 months and at 5 years. We compared the results with
      those of a series of classical TKA in the same category of age and sex. RESULTS:
      The TKA without trochlea posterior fixation presented a significantly reduced
      osteopenia compared to the classical design of the femoral shield. CONCLUSION: It
      seems that the non-fixation of the posterior surface of the trochlea may reduce
      osteopenia in TKA and so the risk of fractures and complications when revision
      surgery. LEVEL OF EVIDENCE: 2a.

PMID- 30116936
TI  - Regional morbidity and mortality during heatwaves in South Australia.
AB  - Heatwaves can be a common occurrence in Australia, and the public health impacts
      can be severe. Heat warnings and interventions are being adopted widely to reduce
      the preventable health impacts. This study examines the effects of heatwaves on
      morbidity and mortality in different climatic regions in the state of South
      Australia, to inform the targeting of heat warnings according to regional needs.
      Heatwaves were defined using the excess heat factor (EHF), an index based on mean
      daily temperature indices that quantifies heatwave severity relative to the local
      climate. In all regions, there were increases in morbidity (daily rates of
      ambulance call-outs and heat-related emergency presentations and hospital
      admissions) on heatwave days compared to non-heatwave days, which increased with
      heatwave severity. This study demonstrates that a consistent measure for heatwave
      severity, based on EHF, can be used to underpin public health warnings for
      climatically diverse areas.

PMID- 30116938
TI  - Challenging the conventional treatment of colon cancer by sentinel lymph node
      mapping and its role of detecting micrometastases for adjuvant chemotherapy.
AB  - All colon cancer patients with lymph node (LN) positive disease are treated with
      chemotherapy. Patients with node negative disease are usually cured by surgery
      alone. Yet about 20% of patients develop recurrence within 5 years despite node
      negative status. This may often be the result of missed micrometastases by
      conventional examination. Sentinel lymph node (SLN) mapping was developed to find
      those nodes detected by blue dye which was ultrastaged to detect micrometastases.
      Consecutive patients, underwent SLN mapping with the blue dye with success rate
      of 99.2%. Average number of LN was 18.3, average number of SLN was 3/patient and
      overall nodal positivity was 45%. Ten patients had skip metastases. Overall
      survival of 235 patients was 84 months with survival of node negative patients 97
      months versus 68 months for node positive patients. For stage I-IV patients,
      overall survival was as follows: stage I-115 months, stage II-90 months, stage
      III-84 months and stage IV-24 months respectively. Patients with micrometastases
      after chemotherapy had average survival of 108 months versus those without
      chemotherapy was 50 months. Thus, SLN mapping techniques is highly successful,
      easily reproducible and finds micrmoetastases in over 15% of patients which could
      have been missed by conventional pathological examination. These patients when
      treated with adjuvant chemotherapy have similar survival as those of node
      negative disease. Similarly, patients without any nodal metastases after SLN
      mapping and ultrastaging, may be considered as true node negative disease and may
      avoid further adjuvant chemotherapy.

PMID- 30116941
TI  - Paradoxical elevation of plasma dabigatran after reversal with idarucizumab in
      stroke thrombolysis.

PMID- 30116939
TI  - Vertebral artery hypoplasia: an innocent lamb or a disguise?
AB  - BACKGROUND: The role of vertebral artery hypoplasia (VAH) in stroke
      pathophysiology is still debated. In this study, we correlated extra- and intra
      cranial vertebral artery ultrasound findings with brain CT/MRI and clinical
      outcome. MATERIALS AND METHODS: We recruited all consecutive first-ever stroke
      patients with a documented acute ischemic brain lesion and a complete extra
      intracranial ultrasound evaluation. Those with previous stroke, or with anterior
      and posterior strokes were excluded. The prevalence of VAH diagnosed by
      ultrasound was recorded both in anterior circulation and posterior circulation
      infarctions. In the latter group, we compared the risk profile, topographic and
      neuroradiological lesion features, etiology and clinical outcome based on the
      presence of VAH. RESULTS: The study included 750 patients [436 males (58%); mean
      age 65 years; age range 18-90] with first-ever acute ischemic stroke: 193 (25.7%)
      with a posterior circulation infarction, 557 (74.3%) with an anterior circulation
      infarction. VAH was more often detected in the former group (33.7 vs. 14.1%; p <
      0.0001). Patients with posterior circulation stroke and VAH had a significantly
      higher frequency of basilar artery stenosis [OR 2.07 (1.00-4.26); p < 0.05],
      stenosis of the contralateral vertebral artery [64 vs. 36%; OR 3.22 (1.24-8.37);
      p < 0.05], and fetal-type variant of the posterior cerebral artery [25 vs. 13%;
      OR 2.17 (1.00-4.68); p < 0.05]. CONCLUSIONS: According to our study, VAH
      identifies patients at higher risk of posterior circulation stroke, and higher
      frequency of contralateral vertebral artery stenosis and basilar artery stenosis.

PMID- 30116940
TI  - Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative
      disease that still lacks reliable diagnostic biomarkers. This study aims to
      evaluate the diagnostic and prognostic potential of CSF total Tau (t-Tau),
      phospho-Tau (p-Tau) and p-Tau/t-Tau ratio in ALS patients using CSF neurofilament
      light (NFL) as the reference biomarker. METHODS: Eighty-five incident ALS, 30 ALS
      mimicking (AM) diseases and 51 other non-neurodegenerative diseases (ONND) were
      included in the study. RESULTS: ALS patients had higher levels of CSF t-Tau and
      lower p-Tau/t-Tau ratio than AM (p = 0.005 and p = 0.006) and ONND (p < 0.001).
      CSF t-Tau levels discriminated ALS from AM with a sensitivity of 69% and
      specificity of 60%, and from ONND with a sensitivity of 88% and specificity of
      51%. These values were lower than the accuracy of CSF NFL in ALS (sensitivity 86%
      and specificity 87% in distinguishing ALS from AM and sensitivity 83% and
      specificity 75% from ONND); CSF t-Tau correlated with progression rate and SNIP.
      CSF p-Tau did not show relation with any ALS clinical features. CSF NFL
      significantly correlated with all considered clinical parameters. High levels of
      CSF t-Tau and NFL were related to poor survival. CONCLUSION: CSF t-Tau showed no
      reliable diagnostic significance but the relation between the high levels of CSF
      t-Tau and short survival suggests the potential prognostic role of this biomarker
      in ALS. However, CSF NFL was confirmed to be the most reliable and efficient tool
      for diagnosis and prediction of clinical progression and survival in ALS
      patients.

PMID- 30116942
TI  - Does normal substantia nigra echogenicity make a difference in Parkinson's
      disease diagnosis? A real clinical practice follow-up study.
AB  - OBJECTIVES: Substantia nigra hyperechogenicity (SN+) detected by transcranial
      ultrasound (TUS) is useful for Parkinson's disease (PD) diagnosis. Approximately
      15% false negative results of unknown significance are reported. However, most
      TUS studies are transversal, and diagnosis of PD may change during follow-up.
      METHODS: Analysis of our prospective registry of TUS in clinical practice,
      selecting patients with sufficient bone window, to whom TUS was performed because
      of suspected PD, and a minimum of 3-year follow-up. Subjects were classified
      regarding SN echogenicity (SN+/SN-). RESULTS: 172 patients (122 SN+, 50 SN-),
      mean age 71 years (25-90), were included. At the end of follow-up, PD diagnosis
      was retained by 91% SN+ vs. 54% SN- subjects (p < 0.0001), while final diagnosis
      of atypical parkinsonism (3%SN+ vs. 16%SN-, p:0.0059) was more frequent in SN-.
      Dopaminergic therapy response was associated with SN+ (88% SN+ vs. 50% SN-, p <
      0.0001), as were abnormal DaTSCANs (90%SN+ vs. 56%SN-, p 0.0027). SN echogenicity
      had 80% sensitivity and 68% specificity for PD diagnosis, while SPECT had 91% and
      73%, respectively. SN+ was the only baseline predictor of keeping PD diagnosis at
      the end of follow-up, with an odds ratio of 12 (95% CI 3-42) (p < 0.001).
      CONCLUSIONS: In our sample of patients with suspected PD, SN hyperechogenicity
      predicted PD diagnosis in the long term with a high odds ratio. Conversely, a
      baseline normal SN echogenicity was associated with a poorer response to PD
      therapy and change to a different diagnosis from PD. Normal SN appears to be a
      caveat for clinicians to check for atypical parkinsonism features during follow
      up.

PMID- 30116943
TI  - Multi-disciplinary proactive follow-up algorithm for patients with advanced NSCLC
      receiving afatinib.
AB  - PURPOSE: Afatinib is a standard first-line therapy for advanced EGFR-positive
      NSCLC. We implemented a pharmacist-led proactive follow-up algorithm to identify
      and manage early afatinib-related adverse events (AEs). METHODS: We conducted a
      retrospective chart review of all patients treated with afatinib after
      implementation of the algorithm at the Sunnybrook Odette Cancer Centre (Toronto,
      ON, Canada) from April 1, 2015 to July 31, 2016. Our in-house algorithm involved
      consultations in person and proactive pharmacist-led callbacks on days 5, 10, and
      17. All AEs were graded and documented in real time and management based on
      toxicity grade was standardized. This study evaluated the impact of our algorithm
      on real-world AEs. RESULTS AND DISCUSSION: Thirty-three patients were identified
      and reviewed. Median follow-up was 248 days. All patients experienced at least
      one drug-related AE; 18.2% were grade 3/4. The most common AEs were diarrhea
      87.9%, rash 81.8%, stomatitis 57.6%, and paronychia 45.5%. Median dose of
      afatinib was 40 mg daily; 51.5% of patients had >= 1 dose reduction and 6.3%
      discontinued afatinib due to AEs. Proactive calls by the pharmacist identified
      36.5% of all drug-related AEs, 33.3% of grade 3/4 AEs, 58.1% of first drug
      related AEs and identified two patients that were non-compliant. Only 3.2% of AEs
      were identified by an emergency room/urgent clinic visit. CONCLUSIONS: This
      proactive multi-disciplinary AE management algorithm resulted in a low rate of
      urgent assessments and discontinuation due to toxicity while maintaining afatinib
      at ideal dose, thus providing a useful tool for centers prescribing afatinib.

PMID- 30116945
TI  - Can Positive Social Perception and Reduced Stigma be a Problem in Sports Betting?
      A Qualitative Focus Group Study with Spanish Sports Bettors Undergoing Treatment
      for Gambling Disorder.
AB  - The way society perceives problem gambling, and its effects on how problem
      gamblers perceive themselves have significant consequences on the wellbeing of
      people experiencing gambling disorder. Associated with social perception, stigma
      and other social perception-related features have an impact on the way problem
      gamblers identify themselves, seek for help, and recover. However, not all
      gambling types are identically perceived by the society. The present paper
      examines the case of the social perception of sports betting in the context of
      Spain. A total of 43 male sports bettors undergoing treatment for gambling
      disorder were interviewed within seven focus group discussions. Using a
      qualitative thematic analysis technique, participants reported two fundamental
      characteristics of sports betting social perception: (1) the absence of negative
      connotations associated with sports betting comparative to other gambling forms;
      and (2) the presence of positive connotations that sanitised sports betting as a
      harmless practice. The study reports aspects such as the lack of stereotypes, the
      low-involvement of betting as a product, the novelty of online sports betting,
      the social construction of the normal bettor, and the workplace gambling
      normalisation as elements that could lead to an increase in gambling-related
      harm. This is the first study to explore the social perception of sports betting
      in a subgroup of problem sports bettors and suggests that policymakers should be
      cognizant of these perceptions in order to inform responsible gambling regulation
      .

PMID- 30116944
TI  - Sexual quality of life evaluation after treatment among women with breast cancer
      under 35 years old.
AB  - PURPOSE: To qualify the quality of patients sexual lives after treatment among
      women with breast cancer under 35 years old and compare results to the
      literature. METHODS: Sexual quality of life was measured for 84 women aged 20 to
      35 years old at diagnosis, with two validated quality of sexual life
      questionnaires, Brief Index of Sexual Functioning for Women (BISF-W) and Female
      Sexual Function Index (FSFI), at least six months after breast cancer diagnosis.
      Two other questionnaires were used to allow us to understand other aspects of
      their life before cancer and to monitor quality of sexual life during treatment.
      RESULTS: Forty-three women responded to the questionnaire. The questionnaires
      demonstrated that more than half of them had problems with their sexuality. The
      mean total score was 28.08/75 for BISF-W and 25.1 for FSFI (under the cutoff
      score 26.55). The domain analysis showed an association between the absence of
      chemotherapy and scores in regard to sexual health. Only 7% had sexual
      disturbance detected but 49% of the patients wished to have it. CONCLUSION:
      Sexual dysfunction in breast cancer survivors is real, has several factors, and
      cannot be evaluated based only on the organic side effects induced by cancer
      treatment. Better monitoring and screening seems necessary in order to optimize
      the quality of sexual life after surviving breast cancer.

PMID- 30116946
TI  - Changes in endogenous phytohormones regulated by microRNA-target mRNAs contribute
      to the development of Dwarf Autotetraploid Chinese Cabbage (Brassica rapa L. ssp.
      pekinensis).
AB  - Polyploidization is considered as the major force that drives plant species
      evolution and biodiversity. The leaves of Chinese cabbage, an important vegetable
      crop valued for its nutritional quality, constitute the main edible organ. In
      this study, we found that autotetraploid Chinese cabbage (Brassica rapa ssp.
      pekinensis) generated from a doubled haploid (DH) line via isolated microspore
      culture exhibits a dwarf phenotype, along with thick leaves and delayed
      flowering. Abscisic acid (ABA) and brassinosteroid (BR) levels were significantly
      lower in autotetraploids compared to DHs. Comparative transcriptome analysis was
      performed to examine the gene regulatory network. A total of 13,225
      differentially expressed genes (DEGs) were detected. Further microRNA (miRNA)
      analysis identified 102 DEGs that correspond to 35 differentially expressed
      miRNAs (DEMs). Subsequent screening of these 102 genes identified 13 key genes
      with 12 corresponding differentially expressed miRNAs that are related to leaf
      development and dwarfism. These 13 genes are involved in the regulation of
      various processes, including BR synthesis (dwarfing), plant growth, flowering
      time delay, ABA pathway-related growth and metabolism, leaf morphology and
      development, and cell extension. Two dwarfing-related genes (BraA01000252 and
      BraA05004386) regulated by two miRNAs (novel_15 and novel_54) were determined to
      be downregulated, indicating their possible role in leaf thickness and dwarfism
      in autotetraploid plants. We also propose two possible miRNA-dependent regulatory
      pathways that contribute to trait formation in autotetraploid Chinese cabbage.
      These results provide a theoretical basis for further work involving Chinese
      cabbage varieties by inducing polyploidy.

PMID- 30116948
TI  - Treatment of Clinically Positive Cervical Lymph Nodes by Limited Local Node
      Excision and Adjuvant Radiotherapy in Melanoma Patients with Major Comorbidities.
AB  - INTRODUCTION: When cervical lymph nodes are clinically positive for metastatic
      melanoma, surgeons may be hesitant to recommend a therapeutic complete lymph node
      dissection if the patient is elderly or has major comorbidities. A limited local
      node excision of the clinically positive nodes only, followed by adjuvant
      radiotherapy to the entire node field, may be an effective alternative in such
      patients. METHODS: All patients who had presented with a primary head and neck
      melanoma or an unknown primary site and had subsequently undergone limited local
      node excision and adjuvant radiotherapy for macroscopically involved cervical
      nodes between 1993 and 2010 at a tertiary referral center were selected for
      study. RESULTS: Twenty-eight patients were identified, with a median age of 78
      years and a median of 2 major comorbidities. The 5-year regional control, disease
      free survival, and overall survival rates were 69%, 44%, and 50%, respectively.
      At the time of data analysis, seven patients were alive without evidence of
      disease. Twenty-one patients had died: 11 of melanoma (4 with neck recurrence)
      and 10 of other causes (2 with neck recurrence). CONCLUSIONS: Excision of
      clinically positive metastatic cervical lymph nodes followed by radiotherapy
      provides satisfactory regional disease control without risking serious morbidity
      or mortality in melanoma patients whose general condition is considered a
      contraindication for therapeutic complete lymph node dissection.

PMID- 30116949
TI  - Frozen Section for Detection of Lymph Nodes After Cervical Injection with
      Indocyanine Green (ICG) for Sentinel Lymph Node Technique in Endometrial Cancer
      Staging.
AB  - OBJECTIVE: The aim of this study was to assess the role of frozen section (FS) in
      identifying an absence of lymph nodes during sentinel lymph node (SLN) biopsy for
      apparent early-stage endometrial cancer (EC). METHODS: Consecutive apparent early
      stage EC patients who had SLNs removed after cervical injection with indocyanine
      green (ICG) from 1 June 2014 to 30 June 2016 were analyzed. An empty node (EN)
      was defined as an SLN specimen without evidence of lymph node(s). The association
      of tumor and patient characteristics with an EN was evaluated, and trend analysis
      to compare the rate of ENs over calendar quarters was performed. A decision-tree
      model was then created to compare the use of FS versus no FS for SLN evaluation
      in the hypothetical cohort affected by early-stage EC in the US each year.
      RESULTS: Over the study period, 300 patients met the inclusion criteria. FS
      revealed ENs in 24 (8%) patients. No association between patient demographic
      characteristics (age, body mass index, prior abdominopelvic surgery,
      international federation of gynecology and obstetrics (FIGO) stage, histology,
      myometrial invasion, cervical stromal invasion) and presence of ENs was observed.
      The rate of ENs at FS did not change over time (p = 0.68). The hypothetical
      analysis showed a 4.3% decrease of inappropriately staged patients with the use
      of FS on the SLN (95% confidence interval 4.1-4.5). CONCLUSIONS: ENs during SLN
      biopsy for EC staging is not a rare event and can be easily detected with FS. The
      implementation of FS of SLN might reduce inadequate staging of EC. Individual
      institutions may want to examine their own EN rates and determine if this would
      assist them in their SLN practices for EC.

PMID- 30116947
TI  - Exogenous application of GA3 inactively regulates axillary bud outgrowth by
      influencing of branching-inhibitors and bud-regulating hormones in apple (Malus
      domestica Borkh.).
AB  - Although gibberellin (GA) has been reported to control branching, little is known
      about how GA mediates signals regulating the outgrowth of axillary buds (ABs). In
      the current study, the effect of the exogenous application of 5.0 mM GA3 on ABs
      outgrowth on 1-year-old 'Nagafu No. 2'/T337/M. robusta Rehd. apple trees was
      investigated and compared to the bud-activating treatments, 5 mM BA or
      decapitation. Additionally, the expression of genes related to bud-regulating
      signals and sucrose levels in ABs was examined. Results indicated that GA3 did
      not promote ABs' outgrowth, nor down-regulate the expression of branching
      repressors [MdTCP40, MdTCP33, and MdTCP16 (homologs of BRANCHED1 and BRC2)],
      which were significantly inhibited by the BA and decapitation treatments. MdSBP12
      and MdSBP18, the putative transcriptional activators of these genes, which are
      expressed at lower levels in BA-treated and decapitated buds, were up-regulated
      in the GA3 treatment in comparison to the BA treatment. Additionally, GA3 did not
      up-regulate the expression of CK response- and auxin transport-related genes,
      which were immediately induced by the BA treatment. In addition, GA3 also up
      regulated the expression of several Tre6P biosynthesis genes and reduced sucrose
      levels in ABs. Sucrose levels, however, were still higher than what was observed
      in BA-treated buds, indicating that sucrose may not be limiting in GA3-controlled
      AB outgrowth. Although GA3 promoted cell division, it was not sufficient to
      induce AB outgrowth. Conclusively, some branching-inhibiting genes and bud
      regulating hormones are associated with the inability of GA3 to activate AB
      outgrowth.

PMID- 30116951
TI  - The effect of distance on short-term outcomes in a regionalized, publicly funded
      bariatric surgery model.
AB  - BACKGROUND: While high-volume Centers of Excellence (COE) for bariatric surgery
      may have improved clinical outcomes, their disparate distribution results in
      longer travel distances for patients. The purpose of this study was to
      investigate effect of distance from COE on outcomes and readmission. METHODS:
      This was a retrospective study of all adults, aged 18 years or older, receiving
      bariatric surgery from April 2009 to March 2012 in the province of Ontario. Main
      outcomes included 30-day complication rates and readmission. Multivariable
      logistic regression was used to examine the impact of distance from patients'
      primary residence to their bariatric COE on patient outcomes and readmissions.
      RESULTS: Five thousand and seven patients were identified, two-thirds residing
      within 100 km of a COE with a mean distance of 117.2 km. The majority of patients
      did not reside within a Local Integrated Health Network (LHIN) that contained a
      COE, while 18.3% of patients lived in rural areas. Using multivariable
      adjustment, for every 10 km increase from the COE where surgery was performed,
      the Odds Ratio (OR) for complications was 1.00 [95% Confidence Interval (CI) 0.99
      1.01; P = 0.747]. Additionally, both residing in a LHIN without a COE, OR 1.10
      (95% CI 0.87-1.40; P = 0.434), and rural status, OR 0.97 (95% CI 0.77-1.23; P =
      0.821) showed no increase in risk of complication. Similarly, further distances
      did not influence rate of readmission, OR 0.99 (95% CI 0.98-1.00; P = 0.077) nor
      did rural status OR 1.31 (95% CI 0.97-1.76; P = 0.076). CONCLUSION: The COE
      model, where a few centers in high population areas service a large geographic
      region, is adequate in ensuring patients that live further away receive
      appropriate short-term care.

PMID- 30116950
TI  - Comparison of synchronous dual wavelength diode laser versus conventional endo
      knives for esophageal endoscopic submucosal dissection: an animal study.
AB  - BACKGROUND: Endoscopic submucosal dissection (ESD) is widely used for en bloc
      resection in early gastrointestinal cancer. However, it is technically complex
      with long procedure time and high adverse event rates with using conventional
      knives. The aim of this animal study was to verify the feasibility of ESD using a
      novel 980/1470 nm dual diode laser (DDL-ESD) in comparison with conventional
      knives (C-ESD) in esophagus. METHODS: This was an in vivo animal study using
      eight porcine models. Four were allocated in DDL-ESD group and four were in C-ESD
      group. Every model underwent two ESDs to remove half circumferential esophageal
      mucosa. Each model's esophagus was harvested during postmortem at 24 h after ESD.
      Each specimen underwent gross inspection and histopathological examination was
      carried out. Procedure time, completeness of en bloc resection, adverse events
      (bleeding and perforation) and histological injury to muscularis propria were
      assessed. RESULTS: A total of 16 ESD procedures were performed with 100% en bloc
      resection rate. The procedure speed in DDL-ESD group was significantly faster as
      compared to C-ESD group (0.27 cm2/min vs. 0.21 cm2/min, p = 0.001). The number of
      intraoperative bleeding points and the use of haemostatic forceps were
      significantly lesser in DDL-ESD group (4 +/- 2 vs. 8 +/- 3, p = 0.016; 1 +/- 1
      vs. 3 +/- 2, p = 0.029). Histological assessment showed that injury to muscularis
      propria in DDL-ESD was milder than C-ESD. There was no perforation observed in
      both groups. CONCLUSIONS: DDL-ESD technique appears to be safer and faster than C
      ESD with less bleeding and injury to deep tissues.

PMID- 30116952
TI  - A case-control study of using carbon nanoparticles to trace decision-making lymph
      nodes around inferior mesenteric artery in rectal cancer.
AB  - BACKGROUND: Accurate identification of lymph nodes localized around inferior
      mesenteric artery (IMA), with or without metastasis, is of crucial importance for
      surgeons when dissecting D2 or D3 lymph nodes in patients with rectal cancer
      (RC). The following study evaluates whether carbon nanoparticles can be used for
      detection of decision-making lymph nodes (DLNs) in station 253 lymph nodes found
      around IMA during RC surgery. METHODS: A total of 66 patients with rectal
      adenocarcinomas were recruited between January 2014 and August 2017. Patients
      were divided into carbon nanoparticle (CN) group and control (CL) group; for the
      CN group, 1 ml nanoparticles were endoscopically injected into submucosal layer
      of primary tumor 1 day before surgery. DLNs were defined as black-dyed nodes in
      CN group or macroscopic lymph nodes in CL group localized along the IMA, proximal
      to the origin of the left colic artery. D3 lymph nodes were dissected using
      laparoscopic radical resection, and then examined using pathological approach.
      Intra-operative and post-operative data were compared between the two groups.
      RESULTS: In CN group, black-dyed DLNs were easily found under laparoscopy; the
      median number of DLNs was 3 (range 1-9). In CL group, the median number of DLNs
      was 0 (range 0-3). Consistency between intra-operative DLNs and post-operative
      station 253 nodes were confirmed by pathological examination. Significant higher
      number of DLNs in station 253 nodes (2.91 +/- 2.47 vs 0.58 +/- 0.75, p < 0.001),
      number of station 251 nodes (12.85 +/- 8.99 vs 8.09 +/- 5.85, p = 0.014), number
      of station 253 nodes (5.21 +/- 5.26 vs 3.15 +/- 2.32, p = 0.045), and the number
      of total lymph nodes (24.06 +/- 13.20 vs 16.21 +/- 9.09, p = 0.007) were found in
      the CN group compared to CL group. CONCLUSIONS: Carbon nanoparticles are useful
      for identifying DLNs in station 253 LNs around IMA in RC. It is not necessary to
      perform D3 lymph node dissection if there are no intra-operative DLNs metastases
      in RC.

PMID- 30116953
TI  - The pivotal role of microRNA-21 in osteoclastogenesis inhibition by anthracycline
      glycoside aloin.
AB  - Osteopenic disorders such as osteoporosis and rheumatoid arthritis are
      characterized by excessive bone resorption by osteoclasts relative to bone
      formation by osteoblasts. MicroRNAs are emerging as key players in bone
      remodeling, modulating the functions of both osteoblasts and osteoclasts. Among
      them, miR-21 is highly expressed in osteoclast precursors and is known to
      regulate genesis, differentiation, and apoptosis of osteoclasts. The pro
      osteoclastogenic nature of miR-21 makes it a potential candidate as a therapeutic
      target to treat bone disorders. We had previously demonstrated that
      anthroglycoside aloin derived from Aloe vera was effective in promoting
      osteoblastogenesis and inhibiting osteoclastogenesis. The present study
      investigated the role of miR-21 in aloin's inhibitory effect on osteoclast
      differentiation. Aloin effectively suppressed receptor activator of nuclear
      factor kappa-B (NFKB) ligand (RankL)-induced miR-21 expression via repression of
      NFKB activation. MiR-21 suppression resulted in upregulation of osteoclast
      suppressor programmed cell death protein 4 (PDCD4), and downregulation of
      osteoclast marker cathepsin K. Knockdown or gain-of-function studies revealed
      that miR-21 was pivotal to aloin's inhibitory effect on osteoclastogenesis. This
      study also highlights the dynamic potential of aloin as a therapeutic agent to
      treat osteopenic disorders.

PMID- 30116955
TI  - Germany: a fair balance between scientific freedom and data subjects' rights?
AB  - With the German Bundestag's adoption of the Data Protection Adaptation and
      Implementation Act EU (DSAnpUG-EU) on 30 June 2017, the adaptation of German law
      to the General Data Protection Regulation (GDPR) has begun (Gesetz zur Anpassung
      des Datenschutzrechts an die Verordnung (EU) 2016/679 und zur Umsetzung der
      Richtlinie (EU) 2016/680 (Datenschutz-Anpassungs- und -Umsetzungsgesetz-DSAnpUG
      EU) v. 30. Juni 2017, BGBl. 2017 I p. 2097 et seq.). Despite being directly
      binding on all EU member states, the GDPR does not render national data
      protection provision obsolete-they are covered by the GDPR's opening clauses
      which include regulatory mandates and room for derogation. This creates
      considerable need for national legislative adaptation. Art. 1 DSAnpUG-EU contains
      the necessary amendments to the Federal Data Protection Law (BDSG(neu)), thus
      creating the second major building block of future German data protection
      alongside the GDPR itself. Nevertheless, there are still numerous sector-specific
      regulations in other federal laws and the data protection laws of the 16 states
      also need amendments. Adjustment in Germany is well on its way, but
      implementation in general is still ongoing, with further consequences for data
      processing and sharing.

PMID- 30116957
TI  - Paper-based 3D printing of anthropomorphic CT phantoms: Feasibility of two
      construction techniques.
AB  - OBJECTIVES: To develop and evaluate methods for assembling radiopaque printed
      paper sheets to realistic patient phantoms for CT dose and image quality testing.
      METHODS: CT images of two patients were radiopaque printed with aqueous potassium
      iodide solution (0.6 g/ml) on paper. Two methods were developed for assembling
      the paper sheets to head and neck phantoms. (1) Printed sheets were fed to a
      paper-based 3D printer along with corresponding 3D printable STL files. (2) Paper
      stacks of 5-mm thickness were glued with toner, cut to the patient shape and
      assembled to a phantom. In a sample application study, both phantoms were
      examined with five different tube current settings. Images were reconstructed
      using filtered-back projection (FBP) and iterative reconstruction (AIDR 3D) with
      three strength levels. Dose length product (DLP), signal-to-noise ratios (SNR)
      and contrast-to-noise ratios (CNRs) were analysed. Data were analysed using 2-way
      analysis of variance (ANOVA). RESULTS: Both methods achieved anthropomorphic
      phantoms with detailed patient anatomy. The 3D printer yielded a precise
      reproduction of the external patient shape, but caused visible glue artefacts.
      Gluing with toner avoided these artefacts and yielded more flexibility with
      regard to phantom size. In the sample application study, non-inferior SNR and CNR
      and up to 83.7% lower DLP were achieved on the phantoms with AIDR 3D compared
      with FBP. CONCLUSIONS: Two methods for assembling radiopaque printed paper sheets
      to phantoms of individual patients are presented. The sample application
      demonstrates potential for simulation of patient imaging and systematic CT dose
      and image quality assessment. KEY POINTS: * Two methods were developed to create
      realistic CT phantoms of individual patients from radiopaque printed paper
      sheets. * Analysis of five tube current and four reconstruction settings on two
      radiopaque 3D printed patient phantoms yielded non-inferior SNR and CNR and up to
      83.7% lower dose with iterative reconstruction in comparison with filtered back
      projection. * Radiopaque 3D printed phantoms can simulate patients and allow
      systematic analysis of CT dose and image quality parameters.

PMID- 30116956
TI  - Australia: regulating genomic data sharing to promote public trust.
AB  - The regulation of genomic data sharing in Australia is a confusing mix of common
      law, legislation, ethical guidelines, and codes of practice. Beyond privacy laws,
      which only apply to genomic data that meets the definition of personal
      information, the key regulatory lever is the National Health and Medical Research
      Council (NHMRC) National Statement for Ethical Conduct in Human Research
      ("National Statement") (2007). Compliance with the National Statement is a
      requirement for institutions to apply to the NHMRC for funding, and includes
      among other things-requirements for review of most genomic research by Human
      Research Ethics Committees. The sections of the National Statement specifying
      requirements for research with human genomic data are currently under review,
      including proposed new requirements addressing the return of genetic research
      findings and oversight of transfer agreements. Ensuring the willingness of
      Australians to donate their genomic information and participate in medical
      research will require clarification and harmonisation of the applicable
      regulatory framework, along with reforms to ensure that these regulations reflect
      the conditions necessary to promote ongoing public trust in researchers and
      institutions.

PMID- 30116958
TI  - Added value of mean and entropy of apparent diffusion coefficient values for
      evaluating histologic phenotypes of invasive ductal breast cancer with MR
      imaging.
AB  - OBJECTIVES: To study the added value of mean and entropy of apparent diffusion
      coefficient (ADC) values at standard (800 s/mm2) and high (1500 s/mm2) b-values
      obtained with diffusion-weighted imaging in identifying histologic phenotypes of
      invasive ductal breast cancer (IDC) with MR imaging. METHODS: One hundred thirty
      four IDC patients underwent diffusion-weighted imaging with b-values of 800 and
      1500 s/mm2, and corresponding ADC800 and ADC1500 maps were generated. Mean and
      entropy of volumetric ADC values were compared with molecular markers (estrogen
      receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor
      2 [HER2], and Ki-67). Associations among morphologic features, ADC metrics, and
      phenotypes (luminal A, luminal B [HER2 negative], luminal B [HER2 positive], HER2
      positive, and triple negative) were evaluated. RESULTS: Mean ADC values were
      significantly decreased in ER-positive, PR-positive, and HER2-negative tumors (p
      < 0.01). Ki-67 >= 20% tumors demonstrated significantly higher ADC entropy values
      compared with Ki-67 < 20% tumors (p < 0.001). Luminal A subtype tended to display
      lower ADC entropy values compared with other subtypes, while HER2-positive
      subtype tended to display higher mean ADC values. ADC1500 entropy provided
      superior diagnostic performance over ADC800 entropy (p = 0.04). Independent risk
      factors were ADC1500 entropy (p = 0.002) associated with luminal A, irregular
      mass shape (p = 0.018) and ADC1500 entropy (p = 0.022) with luminal B (HER2
      positive), mean ADC1500 (p = 0.018) with HER2 positive, and smooth mass margin (p
      = 0.012) and rim enhancement (p = 0.003) with triple negative. CONCLUSIONS: Mean
      and entropy of ADC values provided complementary information and added value for
      evaluating IDC histologic phenotypes. High-b-value ADC1500 may facilitate better
      phenotype discrimination. KEY POINTS: * ADC metrics are associated with molecular
      marker status in IDC. * ADC 1500 improves differentiation of histologic
      phenotypes compared with ADC 800 . * ADC metrics add value to morphologic
      features in IDC phenotyping.

PMID- 30116959
TI  - Radiomics nomogram for predicting the malignant potential of gastrointestinal
      stromal tumours preoperatively.
AB  - OBJECTIVE: To develop and evaluate a radiomics nomogram for differentiating the
      malignant risk of gastrointestinal stromal tumours (GISTs). METHODS: A total of
      222 patients (primary cohort: n = 130, our centre; external validation cohort: n
      = 92, two other centres) with pathologically diagnosed GISTs were enrolled. A
      Relief algorithm was used to select the feature subset with the best
      distinguishing characteristics and to establish a radiomics model with a support
      vector machine (SVM) classifier for malignant risk differentiation. Determinant
      clinical characteristics and subjective CT features were assessed to separately
      construct a corresponding model. The models showing statistical significance in a
      multivariable logistic regression analysis were used to develop a nomogram. The
      diagnostic performance of these models was evaluated using ROC curves. Further
      calibration of the nomogram was evaluated by calibration curves. RESULTS: The
      generated radiomics model had an AUC value of 0.867 (95% CI 0.803-0.932) in the
      primary cohort and 0.847 (95% CI 0.765-0.930) in the external cohort. In the
      entire cohort, the AUCs for the radiomics model, subjective CT findings model,
      clinical index model and radiomics nomogram were 0.858 (95% CI 0.807-0.908),
      0.774 (95% CI 0.713-0.835), 0.759 (95% CI 0.697-0.821) and 0.867 (95% CI 0.818
      0.915), respectively. The nomogram showed good calibration. CONCLUSIONS: This
      radiomics nomogram predicted the malignant potential of GISTs with excellent
      accuracy and may be used as an effective tool to guide preoperative clinical
      decision-making. KEY POINTS: * CT-based radiomics model can differentiate low-
      and high-malignant-potential GISTs with satisfactory accuracy compared with
      subjective CT findings and clinical indexes. * Radiomics nomogram integrated with
      the radiomics signature, subjective CT findings and clinical indexes can achieve
      individualised risk prediction with improved diagnostic performance. * This study
      might provide significant and valuable background information for further studies
      such as response evaluation of neoadjuvant imatinib and recurrence risk
      prediction.

PMID- 30116960
TI  - Pitfalls and problems to be solved in the diagnostic CT/MRI Liver Imaging
      Reporting and Data System (LI-RADS).
AB  - : The 2017 Core of the computed tomography (CT)/magnetic resonance imaging (MRI)
      Liver Imaging Reporting and Data System (LI-RADS) provides clear definitions and
      concise explanations of the CT/MRI diagnostic algorithm. Nevertheless, there
      remain some practical and controversial issues that radiologists should be aware
      of when using the system. This article discusses pitfalls and problems which may
      be encountered when the version 2017 diagnostic algorithm is used for CT and MRI.
      The pitfalls include challenges in applying major features and assigning the LR-M
      category, as well as categorisation discrepancy between CT and MRI. The problems
      include imprecision of category codes, application of ancillary features, and
      regional practice variations in hepatocellular carcinoma (HCC) diagnosis.
      Potential solutions are presented along with these pitfalls and problems. KEY
      POINTS: * Although the diagnostic algorithm provides clear and detailed
      explanations, major feature evaluation can be subject to pitfalls and
      differentiation of HCC and non-HCC malignancy remains challenging. * Ancillary
      features are optional and equally weighted. However, features such as
      hepatobiliary phase hypointensity and restricted diffusion have greater impact on
      HCC diagnosis than other ancillary features and may merit greater emphasis or
      weighting. * LI-RADS was initially developed from a Western paradigm, which may
      limit its applicability in the East due to regional practice variations. In
      Eastern Asia, high sensitivity is prioritised over near-perfect specificity for
      HCC diagnosis in order to detect tumours at early stages.

PMID- 30116962
TI  - Comparison between erbium-doped yttrium aluminum garnet laser therapy and sling
      procedures in the treatment of stress and mixed urinary incontinence.
AB  - PURPOSE: Stress urinary incontinence (SUI) and mixed urinary incontinence (MUI)
      lead to poor quality of life. In Japan, urinary incontinence is treated with
      tension-free vaginal tape (TVT) or transobturator tape (TOT) sling procedures,
      which involves inserting a synthetic material; however, problems arise with
      artificial mesh in some instances, requiring new treatment methods. Hence, laser
      therapy, whereby an erbium-doped yttrium aluminum garnet laser is directed into
      the vagina and urethra, may be useful. The study aimed to compare the effects of
      these three treatments. METHODS: Subjects included patients who received TVT,
      TOT, or laser therapy (n = 50 each). The 1-h pad test, International Consultation
      on Incontinence Questionnaire Short Form (ICIQ-SF), and overactive bladder
      symptom score were used to assess the patients before and 12 months after
      treatment. For laser therapy, a probe was inserted into the vagina after applying
      a local anesthetic to the vaginal wall, and irradiation was performed for 20 min
      at a wavelength of 2940 nm. This treatment was performed three times every
      alternate month. RESULTS: As per the 1-h pad test and ICIQ-SF, the TVT, TOT, and
      laser therapy groups showed comparable improvements in SUI. For patients with
      MUI, some in the TVT and TOT groups showed exacerbation; however, all patients in
      the laser therapy group tended to improve. CONCLUSIONS: The efficacy of laser
      therapy for urinary incontinence was confirmed. This is the first study to report
      on the effect of laser therapy on urinary incontinence in Japanese women.

PMID- 30116961
TI  - CT texture analysis of pancreatic cancer.
AB  - OBJECTIVES: We investigated the value of CT texture analysis (CTTA) in predicting
      prognosis of unresectable pancreatic cancer. METHODS: Sixty patients with
      unresectable pancreatic cancers at presentation were enrolled for post-processing
      with CTTA using commercially available software (TexRAD Ltd, Cambridge, UK). The
      largest cross-section of the tumour on axial CT was chosen to draw a region-of
      interest. CTTA parameters (mean value of positive pixels (MPP), kurtosis,
      entropy, skewness), arterial and venous invasion, metastatic disease and tumour
      size were correlated with overall and progression-free survivals. RESULTS: The
      median overall and progression-free survivals of cohort were 13.3 and 7.8 months,
      respectively. On multivariate Cox proportional hazard regression analysis,
      presence of metastatic disease at presentation had the highest association with
      overall survival (p = 0.003-0.05) and progression-free survival (p < 0.001 to p =
      0.004). MPP at medium spatial filter was significantly associated with poor
      overall survival (p = 0.04). On Kaplan-Meier survival analysis of CTTA parameters
      at medium spatial filter, MPP of more than 31.625 and kurtosis of more than 0.565
      had significantly worse overall survival (p = 0.036 and 0.028, respectively).
      CONCLUSIONS: CTTA features were significantly associated with overall survival in
      pancreas cancer, particularly in patients with non-metastatic, locally advanced
      disease. KEY POINTS: * CT texture analysis is easy to perform on contrast
      enhanced CT. * CT texture analysis can determine prognosis in patients with
      unresectable pancreas cancer. * The best predictors of poor prognosis were high
      kurtosis and MPP.

PMID- 30116963
TI  - Extra-target low-risk prostate cancer: implications for focal high-intensity
      focused ultrasound of clinically significant prostate cancer.
AB  - PURPOSE: To analyse the impact of the presence of extra-target non-clinically
      significant cancer (NCSC) after high-intensity focused ultrasound (HIFU)
      hemiablation on oncological results. To analyse radical treatment free survival
      (RTFS) rates at 2-3 years follow-up. METHODS: Retrospective single-centre study
      of 55 patients treated by primary HIFU hemiablation from 2010 to 2016. Inclusion
      criteria were unilateral MRI detected CSC, stage <= T2b, Gleason score (GS) <= 7,
      at least 6 mm distant from prostate apex. MRI with systematic and targeted
      biopsies was performed at diagnosis. Follow-up included clinical examination, PSA
      every 6 month, MRI and biopsies at 1 year and in case of PSA elevation. HIFU
      retreatment was possible. Whole-gland treatment was indicated in case of positive
      biopsies with GS >= 7 or maximum cancer core length > 5 mm, any GS. RESULTS: Mean
      follow-up was 33 months (SD: 17-49 months). Presence or not of an extra-target
      NCSC in the untreated part of the gland had no impact on RTFS at univariate
      analysis (p = 0.29). 10 (18%) patients had a salvage whole-gland treatment after
      a median follow-up of 26 months (IQR 17-28). RTFS at 2 and 3 years were 92% and
      80%. CONCLUSION: Presence or not of an extra-target NCSC in the untreated part of
      the gland had no impact on RTFS. NCSC lesion can be left untreated and actively
      monitored. RTFS was 80% at 3 years which support the concept of focal/partial
      treatment as a treatment option of CSC prostate cancer.

PMID- 30116964
TI  - Photovaporization of the prostate with GreenLightTM laser 180 W XPS versus
      transurethral resection of the prostate with monopolar energy for the treatment
      of benign prostatic enlargement: a cost-utility analysis from a healthcare
      perspective.
AB  - PURPOSE: To assess the cost-utility of the photovaporization of the prostate
      (PVP) with GreenLightTM laser 180 W XPS compared to transurethral resection of
      the prostate with monopolar energy (M-TURP) for lower urinary tract symptoms
      (LUTS) due to benign prostatic enlargement (BPE) from a healthcare perspective in
      Colombia. METHODS: We designed a Markov model to compare four health states
      following treatment with either PVP or M-TURP to estimate expected costs and
      outcomes. We used the results of the only randomized clinical trial published to
      date comparing PVP versus M-TURP to estimate surgical outcomes, complications, re
      operation and re-intervention rates. Time horizon was defined at 2 years with
      four cycles of 6 months each. Resource-use estimation involved a random selection
      of clinical records from a local institution and cost list from public healthcare
      system. Costs were obtained in Colombian pesos and converted to US dollars.
      Threshold was defined at three-times the Colombian gross domestic product (GDP)
      per capita. Quality-adjusted-life-years (QALYs) were used based on the utilities
      of the available literature. Uncertainty was analyzed with deterministic and
      probabilistic models using a Monte Carlo simulation. RESULTS: Patients who
      underwent PVP gained 1.81 QALYs compared to 1.59 with M-TURP. Costs were
      US$6797.98 and US$7777.59 for M-TURP and PVP, respectively. Incremental cost
      effectiveness ratio was US$4452.81 per QALY, favoring PVP as a cost-effective
      alternative in our context. CONCLUSIONS: In Colombia, with current prices, PVP is
      cost-effective when compared to M-TURP for LUTS due to BPE for a 2-year time
      horizon.

PMID- 30116965
TI  - Human Cutaneous Protothecosis: A Case Report and Review of Cases from Mainland
      China, Hong Kong, and Taiwan.
AB  - We present a case of cutaneous protothecosis caused by Prototheca wickerhamii
      infection. The patient was a 72-year-old man with hypoalbuminemia. He responded
      well to fluconazole treatment. We reviewed this case along with 17 other cases of
      cutaneous protothecosis reported from mainland China, Hong Kong, and Taiwan. Of
      the 18 cases, 7 each occurred in mainland China and Taiwan, and 4 occurred in
      Hong Kong. Thirteen cases were caused by P. wickerhamii (72.2%), and three were
      caused by P. zopfii (16.7%); in two cases, the species was not identified
      (11.1%). In all, 9 (50%) patients were immunocompromised, and 10 (55.5%) patients
      denied having a history of trauma. All patients presented with polymorphic skin
      lesions, and erythematous papules, plaques, or nodules was the most common
      presentation (15/18, 83.3%). Genotyping was performed in five cases, mostly by
      means of small subunit ribosomal DNA amplification (four cases). Susceptibility
      tests (6 patients) showed that P. wickerhamii was sensitive to amphotericin B and
      voriconazole but resistant to fluconazole or itraconazole. Treatment succeeded in
      15 (83.3%) patients and failed in 3 (16.7%). Our data indicate that the number of
      cutaneous protothecosis cases is underestimated in China, and the skin lesions
      have some diagnostic value.

PMID- 30116967
TI  - The Influence of Psychological Needs and Exercise Motivation on Exercise
      Dependence among Chinese College Students.
AB  - To explore the influence of exercise motivation and basic psychological needs on
      exercise dependence among Chinese college students. 1689 college students engaged
      in long-term exercise were selected from three universities in Hunan province in
      China as the objects of the survey. 1601 valid copies of the questionnaire were
      collected. Exercise Addiction Inventory, Motivation for Physical Activity Measure
      Revised, Psychological Need Satisfaction in Exercise Scale and other
      questionnaires were used in the correlation analysis and structural equation
      model to investigate the influence of psychological needs and exercise motivation
      on exercise dependence among Chinese college students. Appearance motivation and
      ability motivation directly affect exercise dependence positively (r = 0.303, r =
      0.269), while competence need directly affects exercise dependence positively (r
      = 0.309), and indirectly affects exercise dependence through appearance
      motivation and ability motivation. Appearance motivation and ability motivation
      directly affect exercise dependence positively; competence need not only directly
      affects exercise dependence but also indirectly affects it through appearance and
      ability.

PMID- 30116966
TI  - Next-generation sequence data demonstrate several pathogenic bee viruses in
      Middle East and African honey bee subspecies (Apis mellifera syriaca, Apis
      mellifera intermissa) as well as their cohabiting pathogenic mites (Varroa
      destructor).
AB  - RNA viruses are associated with honey bee (Apis mellifera) colony losses in many
      parts of the world. Their consequences may be exacerbated when the ectoparasite
      mite Varroa destructor is present in hives. While evidence of pathogenic, viral
      induced disease is abundant in western honey bees (Apis mellifera mellifera) from
      many parts of the world, less information exists regarding the pathogen load of
      Apis mellifera syriaca and Apis mellifera intermissa, honey bees from the Middle
      East and North Africa (MENA) that play substantial roles in regional beekeeping.
      Here, we used next-generation sequencing to evaluate the viral populations of
      these subspecies and their associated mites. We found that both A. m. syriaca and
      A. m. intermissa, as well as the Varroa mites infecting their colonies, bear a
      suite of RNA viruses including major pathogenic viruses like Deformed wing virus,
      Acute bee paralysis virus, Black queen cell virus and Sacbrood virus, and less
      common viruses (e.g., bee Macula-like virus and Apis mellifera filamentous
      virus). The two native honey bee MENA subspecies have acquired different but
      overlapping suites of pathogens, which also differ, but overlap, with the suites
      detected in the mites. The presence of plant viruses suggests that they were
      acquired from foraging for pollen and nectar. Phylogenetic analysis of the above
      common pathogenic RNA viruses showed unexpected genetic relationships with other
      known strains, indicative of import to MENA from outside of the region. Our
      findings indicate that it is important to carefully consider the impact of the
      movement of queens and mobile colonies, and the effects such movement have, on
      the transmission of disease.

PMID- 30116968
TI  - Compensatory force measurement and multimodal force feedback for remote
      controlled vascular interventional robot.
AB  - Minimally invasive vascular interventional surgery is widely used and remote
      controlled vascular interventional surgery robots (RVIRs) are being developed to
      reduce the occupational risk of the intervening physician in minimally invasive
      vascular interventional surgeries. Skilled surgeon performs surgeries mainly
      depending on the detection of collisions. Inaccurate force feedback will be
      difficult for surgeons to perform surgeries or even results in medical accidents.
      In addition, the surgeon cannot quickly and easily distinguish whether the
      proximal force exceeds the safety threshold of blood vessels or not, and thus it
      results in damage to the blood vessels. In this paper, we present a novel method
      comprising compensatory force measurement and multimodal force feedback (MFF).
      Calibration experiments and performance evaluation experiments were carried out.
      Experimental results demonstrated that the proposed method can measure the
      proximal force of catheter/guidewire accurately and assist surgeons to
      distinguish the change of proximal force more easily. This novel method is
      suitable for use in actual surgical operations.

PMID- 30116969
TI  - Origins of stream salinization in an upland New England watershed.
AB  - Salinity levels are above historical levels in many New England watersheds. We
      investigated potential sources of salinity in the Pemigewasset River, a
      relatively undeveloped watershed in northern New England. We utilized a synoptic
      sampling approach on six occasions between April and September 2011 paired with a
      novel land use analysis that incorporated traditional watershed and riparian
      zones as well as a local contributing area. We established background specific
      conductivity (SC) and found that SC was above established background levels in
      both the mainstem of the river (peak of 172 MUS cm-1) and multiple tributaries.
      Specific conductivity was highest during low flow conditions (June) indicating
      potential groundwater storage and release of de-icing salts applied during winter
      months. Development in the watershed and riparian zone was found to be more
      strongly associated with elevated SC, compared to roads. The local contributing
      area was not found to be strongly associated with SC; however, there was evidence
      that the local contributing area may contribute to SC under low flow conditions.

PMID- 30116970
TI  - 68Ga-PSMA-PET: added value and future applications in comparison to the current
      use of choline-PET and mpMRI in the workup of prostate cancer.
AB  - Positron emission tomography (PET) has been commonly and successfully used, in
      combination with computed tomography (CT) and more recently magnetic resonance
      (MRI), in the workup of intermediate or high-risk prostate cancer (PCa).
      Nowadays, new specific receptor targeted PET tracers in prostate cancer imaging
      have been introduced; one of the most used is 68Ga-PSMA, that evaluates the
      expression of prostate-specific membrane antigen (PSMA). This tracer has been
      rapidly taken into account for its better sensitivity and specificity compared to
      lipid metabolism tracers, such as 11C/18F labelled fluorocholine. Besides, in the
      era of theranostics, this tracer is having a useful application not only for
      imaging but also for therapeutic purposes. The aim of this review article is, in
      the first part, to give an overview of the main indications and future
      development of 68Ga-PSMA imaging, using PET/CT or PET/MRI, according to the
      clinical course of the disease and in view of the current use of multiparametric
      MRI (mpMRI) and choline PET in the management of PCa. In the second part, a brief
      overview of the promising 18F-labelled PSMA tracers and the current use of PSMA
      radionuclide therapy will be provided.

PMID- 30116973
TI  - Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal
      Tract and Cultured Enteric Neurons and Glial Cells.

PMID- 30116972
TI  - A review of feeding intolerance in critically ill children.
AB  - Ensuring optimal nutrition is vital in critically ill children and enteral
      feeding is the main route of delivery in intensive care. Feeding intolerance is
      the most commonly cited reason amongst pediatric intensive care unit healthcare
      professionals for stopping or withholding enteral nutrition, yet the definition
      for this remains inconsistent, nebulous, and entirely arbitrary. Not only does
      this pose problems clinically, but research in this field frequently uses feeding
      intolerance as an endpoint and the heterogeneity in this definition makes the
      comparison of studies difficult and meta-analysis impossible. We reviewed the use
      of, and definitions of, the term feed intolerance in pediatric intensive care
      research papers in the last 20 years. Gastric residual volume remains the most
      common factor used to define feed intolerance, despite the lack of evidence for
      this. Healthcare professionals would benefit from further education to improve
      their awareness of the limitations of the markers to define feeding intolerance,
      and the international PICU community needs to agree a consistent definition of
      this phenomenon to improve consistency in both practice and research.Conclusion:
      This paper will provide a narrative review of the definitions of, evidence for,
      and markers of feeding intolerance in critically ill children. What is Known?: *
      Feeding intolerance is a commonly cited reason amongst pediatric intensive care
      unit healthcare professionals for stopping or withholding enteral nutrition. *
      There is no agreed definition for feeding intolerance in critically ill children.
      What is New?: * This paper provides an up to date review of the definitions of,
      evidence for, and markers of feeding intolerance in critically ill children. *
      Despite no evidence, gastric residual volume continues to drive clinical bedside
      decisions about enteral feeding and feeding tolerance.

PMID- 30116971
TI  - Medically induced CSF rhinorrhea following treatment of macroprolactinoma: case
      series and literature review.
AB  - PURPOSE: Although several reports have addressed cerebrospinal fluid (CSF)
      rhinorrhea following dopamine agonist (DA) therapy of macroprolactinomas, further
      study is warranted for this relatively uncommon entity. Toward this aim, our
      retrospective series and review of literature further clarifies recommendations
      in treatment of this rare problem. METHODS: We retrospectively reviewed all
      macroprolactinoma cases in our hospital for a 15-year period. Our systematic
      search of PubMed identified original articles and reviews of all
      macroprolactinoma cases with an associated medication-induced CSF leak. RESULTS:
      Five patients with drug-induced CSF leak were identified; four of these patients
      received cabergoline therapy an average of 6 weeks before the onset of rhinorrhea
      and then underwent surgical repair of the CSF leak. Of 35 published studies
      included, we identified 60 patients with medication-induced CSF leak. Medical
      therapy included bromocriptine in 34 patients, cabergoline in 21 patients, and
      use of both DAs in two patients. Three cases did include complete diagnostic and
      treatment data. Median time from initiation of the DA treatment to occurrence of
      rhinorrhea was 6 weeks. For CSF rhinorrhea, 49 patients underwent surgical repair
      (38 by the transnasal approach) and seven patients were treated nonoperatively.
      CONCLUSION: Baseline skull base erosion in macroprolactinomas in combination with
      subsequent tumor shrinkage induced by DA therapy may result in spontaneous CSF
      rhinorrhea. Therefore, such patients should be advised about and monitored for
      this potential setback. Once CSF leak is diagnosed, prompt treatment must be
      carried out to avoid infectious complications. Transnasal surgery appears the
      most effective therapeutic approach.

PMID- 30116974
TI  - Doing it All - How Families are Reshaping Rare Disease Research.
AB  - The face of rare disease drug discovery and development is changing right before
      our eyes. The outliers of the past were the plucky parents who summoned up the
      courage to try to treat their children against all odds. Think of the rare
      disease focused movies 'Lorenzo's Oil' and 'Extraordinary Measures' but now
      accelerated to develop treatments even quicker. Parents, patient advocates and
      their collaborators are now capable of doing it all themselves. We think this
      will have profound implications for everyone from the incumbent rare disease
      foundations that have held sway for decades to the multibillion dollar rare
      disease market, BioPharma companies, VCs and angel investors that inhabit this
      space. The repercussions of this disruption will no doubt impact healthcare in
      general and ultimately influence how we develop treatments for major diseases as
      well. We present several lines of evidence for our viewpoint from our personal
      experiences interacting with many rare disease families and patient advocates in
      recent years.

PMID- 30116975
TI  - Vertebral Fracture Identification as Part of a Comprehensive Risk Assessment in
      Patients with Osteoporosis.
AB  - PURPOSE OF REVIEW: To review current evidence regarding the vertebral fracture
      prevalence, the accuracy of vertebral fracture identification on current imaging
      technologies, and the potential impact of vertebral fracture identification on
      fracture risk. RECENT FINDINGS: Important new studies have clarified the features
      of prevalent vertebral fracture that most strongly predict incident fractures.
      Age- and sex-stratified estimates of vertebral fracture prevalence on
      densitometric lateral spine images in the US population are now available. The
      accuracy of densitometric vertebral fracture assessment, how computed tomography
      scans and other spinal images obtained for indications other than vertebral
      fracture assessment can be leveraged to detect prevalent vertebral fractures, and
      the potential impact of vertebral fracture assessment on patient and provider
      fracture risk management behavior have been clarified. Substantial progress has
      been made regarding screening strategies using lateral spine imaging to detect
      prevalent vertebral fracture in the older population. Further research regarding
      implementation of these strategies in clinical practice and their impact on
      clinical outcomes is needed.

PMID- 30116977
TI  - The Processing of Grammatical Gender Agreement in Brazilian Portuguese: ERP
      Evidence in Favor of a Single Route.
AB  - The present study used event-related potentials to investigate whether the
      processing of grammatical gender agreement involving gender regular and irregular
      forms recruit the same or distinct neurocognitive mechanisms and whether
      different grammatical gender agreement conditions elicit the same or diverse ERP
      signals. Native speakers of Brazilian Portuguese read sentences containing
      congruent and incongruent grammatical gender agreement between a determiner and a
      regular or an irregular form (condition 1) and between a regular or an irregular
      form and an adjective (condition 2). However, in condition 2, trials with
      incongruent regular forms elicited more positive ongoing waveforms than trial
      with incongruent irregular forms. We found a biphasic LAN/P600 effect for gender
      agreement violation involving regular and irregular forms in both conditions. Our
      findings suggest that gender agreement between determiner and nouns recruits the
      same neurocognitive mechanisms regardless of the nouns' form and that, depending
      on the grammatical class of the words involved in gender agreement, differences
      in ERP signals can emerge.

PMID- 30116976
TI  - The Effects of Homocysteine on the Skeleton.
AB  - PURPOSE OF REVIEW: Homocystinuria is a congenital metabolic disorder in which
      cystathionine beta-synthase deficiency results in a prominent increase in
      homocysteine (serum levels > 100 MUM), causing mental retardation,
      atherosclerotic cerebral infarction, and osteoporosis accompanied by fragility
      fractures. Encountering a case with excessive homocysteinemia such as that seen
      in hereditary homocystinuria is unlikely during usual medical examinations.
      However, in individuals who have vitamin B or folate deficiency, serum
      homocysteine concentrations are known to increase. These individuals may also
      have a polymorphism in methylenetetrahydrofolate reductase, MTHFR (C677T: TT
      type), which regulates homocysteine metabolism. These changes in homocysteine
      levels may elicit symptoms resembling those of homocystinuria (e.g., Alzheimer's
      disease, atherosclerosis, osteoporosis). RECENT FINDINGS: High serum homocysteine
      has been shown to have detrimental effects on neural cells, vascular endothelial
      cells, osteoblasts, and osteoclasts. Homocysteine is also known to increase
      oxidative stress, disrupt cross-linking of collagen molecules, and increase
      levels of advanced glycation end products, which results in reduced bone strength
      through a mechanism that goes beyond low bone density and increased bone
      resorption. Therefore, high serum homocysteine may be regarded as a factor that
      can reduce both bone mass and impair bone quality. In this review, we outline the
      epidemiology and pathophysiology of osteoporosis associated with
      hyperhomocysteinemia.

PMID- 30116980
TI  - Parkinsonism and multiple sclerosis, what is behind?

PMID- 30116978
TI  - L-Glutamate nutrition and metabolism in swine.
AB  - L-Glutamate (Glu) has traditionally not been considered as a nutrient needed in
      diets for humans and other animals (including swine) due to the unsubstantiated
      assumption that animals can synthesize sufficient amounts of Glu to meet their
      needs. The lack of knowledge about Glu nutrition has contributed to suboptimal
      efficiency of global livestock production. Over the past 25 years, there has been
      growing interest in Glu metabolism in the pig, which is an agriculturally
      important species and also a useful model for studying human biology. Because of
      analytical advances in its analysis, Glu is now known to be a highly abundant
      free amino acid in milk and intracellular fluid, a major constituent of food and
      tissue proteins, and a key regulator of gene expression, cell signaling, and anti
      oxidative reactions. Emerging evidence shows that dietary supplementation with 2%
      Glu maintains gut health and prevents intestinal dysfunction in weanling piglets,
      while enhancing their growth performance and survival. In addition, the inclusion
      of 2% Glu is required for dietary arginine to maximize the growth performance and
      feed efficiency in growing pigs, whereas dietary supplementation with 2% Glu
      reduces the loss of skeletal muscle mass in endotoxin-challenged pigs.
      Furthermore, supplementing 2% Glu to a corn- and soybean-meal-based diet promotes
      milk production by lactating sows. Thus, an adequate amount of dietary Glu as a
      quantitatively major nutrient is necessary to support maximum growth,
      development, and production performance of swine. These results also have
      important implications for improving the nutrition and health of humans and other
      animals.

PMID- 30116979
TI  - Comparison of methods for estimation of the intravoxel incoherent motion (IVIM)
      diffusion coefficient (D) and perfusion fraction (f).
AB  - OBJECTIVE: Intravoxel incoherent motion (IVIM) shows great potential in many
      applications, e.g., tumor tissue characterization. To reduce image-quality
      demands, various IVIM analysis approaches restricted to the diffusion coefficient
      (D) and the perfusion fraction (f) are increasingly being employed. In this work,
      the impact of estimation approach for D and f is studied. MATERIALS AND METHODS:
      Four approaches for estimating D and f were studied: segmented IVIM fitting,
      least-squares fitting of a simplified IVIM model (sIVIM), and Bayesian fitting of
      the sIVIM model using marginal posterior modes or posterior means. The estimation
      approaches were evaluated in terms of bias and variability as well as ability for
      differentiation between tumor and healthy liver tissue using simulated and in
      vivo data. RESULTS: All estimation approaches had similar variability and ability
      for differentiation and negligible bias, except for the Bayesian posterior mean
      of f, which was substantially biased. Combined use of D and f improved tumor-to
      liver tissue differentiation compared with using D or f separately. DISCUSSION:
      The similar performance between estimation approaches renders the segmented one
      preferable due to lower numerical complexity and shorter computational time.
      Superior tissue differentiation when combining D and f suggests complementary
      biologically relevant information.

PMID- 30116981
TI  - Prevalence of restless legs syndrome in individuals with migraine: a systematic
      review and meta-analysis of observational studies.
AB  - OBJECTIVE: Recent studies have shown an association between migraine and restless
      legs syndrome (RLS), but RLS prevalence among individuals with migraine differs
      substantially across studies. The present work aimed to comprehensively assess
      available evidence to estimate RLS prevalence among individuals with migraine and
      non-migraine controls. METHOD: Web of Science, PubMed, Embase, Chinese National
      Knowledge Infrastructure, Wanfang, and SinoMed databases were searched for
      observational and case-control studies of RLS prevalence among individuals with
      migraine. Eligible studies were meta-analyzed using Stata 12.0 software. RESULTS:
      Pooled RLS prevalence in migraine was 19%, and the prevalence was lower in Asia
      (16%) than outside Asia (21%). Pooled RLS prevalence was 18.8% among individuals
      with migraine with aura, and 18.5% among individuals with migraine without aura;
      the RLS prevalence in migraine with aura (MA) was higher than that of migraine
      without aura (MO) (OR 1.17, 95%CI 1.01-1.34; p = 0.037). Pooled RLS prevalence in
      a case-control study was significantly higher among individuals with migraine
      (17.9%) than among non-migraine controls (7.1%) (OR 2.65, 95%CI 2.26-3.10; p <
      0.001). CONCLUSION: Our meta-analysis provides the first reliable pooled estimate
      of RLS prevalence among individuals with migraine, and it provides strong
      evidence that RLS risk is higher among individuals with migraine than among
      controls.

PMID- 30116982
TI  - Predicting Growth Traits with Genomic Selection Methods in Zhikong Scallop
      (Chlamys farreri).
AB  - Selective breeding is a common and effective approach for genetic improvement of
      aquaculture stocks with parental selection as the key factor. Genomic selection
      (GS) has been proposed as a promising tool to facilitate selective breeding.
      Here, we evaluated the predictability of four GS methods in Zhikong scallop
      (Chlamys farreri) through real dataset analyses of four economical traits (e.g.,
      shell length, shell height, shell width, and whole weight). Our analysis revealed
      that different GS models exhibited variable performance in prediction accuracy
      depending on genetic and statistical factors, but non-parametric method,
      including reproducing kernel Hilbert spaces regression (RKHS) and sparse neural
      networks (SNN), generally outperformed parametric linear method, such as genomic
      best linear unbiased prediction (GBLUP) and BayesB. Furthermore, we demonstrated
      that the predictability relied mainly on the heritability regardless of GS
      methods. The size of training population and marker density also had considerable
      effects on the predictive performance. In practice, increasing the training
      population size could better improve the genomic prediction than raising the
      marker density. This study is the first to apply non-linear model and neural
      networks for GS in scallop and should be valuable to help develop strategies for
      aquaculture breeding programs.

PMID- 30116983
TI  - Virus preparations from the mixed-infected P70 Pinot Noir accession exhibit GLRaV
      1/GVA 'end-to-end' particles.
AB  - P70 is a Pinot Noir grapevine accession that displays strong leafroll disease
      symptoms. A high-throughput sequencing (HTS)-based analysis established that P70
      was mixed-infected by two variants of grapevine leafroll-associated virus 1
      (GLRaV-1, genus Ampelovirus) and one of grapevine virus A (GVA, genus Vitivirus)
      as well as by two viroids (hop stunt viroid [HSVd] and grapevine yellow speckle
      viroid 1 [GYSVd1]) and four variants of grapevine rupestris stem pitting
      associated virus (GRSPaV). Immunogold labelling using gold particles of two
      different diameters revealed the existence of 'hybrid' particles labelled at one
      end as GLRaV-1, with the rest labelled as GVA. In this work, we suggest that
      immunogold labelling can provide information about the biology of the viruses,
      going deeper than just genomic information provided by HTS, from which no
      recombinant or 'chimeric' GLRaV-1/GVA sequences had been identified in the
      dataset. Our observations suggest an unknown interaction between members of two
      different viral species that are often encountered together in a single
      grapevine, highlighting potential consequences in the vector biology and
      epidemiology of leafroll and rugose-wood diseases.

PMID- 30116984
TI  - Identification of a conserved neutralizing epitope in the G-protein of Chandipura
      virus.
AB  - Chandipura virus (CHPV), associated with an encephalitic illness in humans, has
      caused multiple outbreaks with high mortality in central and western India in
      recent years. The present study compares surface glycoprotein (G-protein) from
      prototype and recent outbreak strains using in silico tools and in vitro
      experiments. In silico epitope predictions (B-cell and T-helper cell) for the
      sequences, 3D structure prediction and comparison of the G-proteins of the
      strains: I653514 (Year 1965), CIN0327 (Year 2003) and 148974 (Year 2014) revealed
      that the CHPV G-protein is stable and antigenic determinants are conserved. A
      monoclonal antibody developed against strain CIN0327 (named NAbC) was found to
      neutralize prototype I653514 as well as the currently circulating strain 148974.
      In silico antigen-antibody interaction studies using molecular docking of
      predicted structures of NAbC and G-proteins of various CHPV strains led to the
      identification of a conserved neutralizing epitope in the fusion domain of G
      protein, which also contained a putative T-helper peptide. The identification of
      a conserved neutralizing epitope in domain IV (fusion domain amino acids 53 to
      172) of CHPV G-protein is an important finding that may have the scope towards
      the development of protective targets against CHPV infection.

PMID- 30116986
TI  - Pre-therapy CT scan showing peritoneal thickening from metastatic renal pelvis
      carcinoma patients.
AB  - : We investigated clinical significance of peritoneal thickening from metastatic
      renal pelvis based on pretherapy computed tomography (CT) scan findings. The
      criteria for inclusion were as follows: (1) pathology and CT scan confirmed
      metastatic renal pelvis carcinoma and (2) peritoneal thickening based on pre
      therapy CT scan findings. We investigated the route of spread, gastrointestinal
      (GI) complications, and response to chemotherapy. A total of 68 cases were
      enrolled in this study, including seven patients with liver metastases and three
      with abdominal wall invasion. GI complications included obstruction in ten
      patients and bleeding in three. Response to chemotherapy demonstrated by reduced
      peritoneal thickening was noted in 24 patients. IN CONCLUSION: peritoneal
      thickening with clinical suspicion of peritoneal involvement can get indirect
      evidence from route of spread (liver or abdominal wall), GI complications
      (obstruction or bleeding) or response to chemotherapy (obvious decrease
      peritoneal thickening) from metastatic renal pelvis carcinoma patients.
      Pretherapy CT scan with peritoneal thickening should be alert that tumor has
      spread to the peritoneum.

PMID- 30116987
TI  - The timing of fusion surgery for clival chordoma with occipito-cervical joint
      instability: before or after tumor resection?
AB  - Clival chordoma with occipito-cervical (OC) joint invasion can result in
      preoperative and postoperative instability. The authors investigate the
      appropriate timing of OC fusion to prevent instability-, fusion-, and surgery
      time-related morbidity. Twenty-two consecutive patients underwent surgery for
      clival chordoma from December 2008 to September 2014. OC fusion was performed for
      patients with OC joint invasion and instability due to preoperative destruction
      of the occipital condyle or extensive postoperative condylectomy. The data in
      relation to OC joint instability, fusion, and surgery time were analyzed
      retrospectively and compared between OC fusion before and after tumor resection.
      Of the 22 patients, 8 with tumor invasion of the OC joint underwent OC fusion. OC
      fusion was performed after tumor resection in one-stage for four patients and
      before tumor resection in two-stage for four patients. There was OC joint
      instability from tumor destruction of the occipital condyle in seven patients
      (87.5%). Patients with OC fusion after tumor resection encountered complications
      such as surgery site wound dehiscence, encephalitis, and cardiac arrest with
      consequent mortality in one patient. These complications were avoided in
      subsequent patients where OC fusion was performed before tumor resection. There
      were no differences in the extent of tumor resection between OC fusion before and
      after tumor resection. Two-stage OC fusion before tumor resection can reduce
      instability-, fusion-, and surgery time-related morbidity and achieve feasible
      tumor resection when OC joint instability is expected. The extent of tumor
      invasion and brain stem compression should be considered when fusion precedes
      tumor resection.

PMID- 30116985
TI  - Enhanced Endoscopy in Bladder Cancer.
AB  - PURPOSE OF REVIEW: Endoscopy coupled with targeted resections represents a
      cornerstone in the diagnosis, staging, and treatment of patients with bladder
      cancer. Direct visualization can be challenging and imprecise due to patient-,
      tumor-, and surgeon-specific factors. We will review contemporary endoscopic
      technologies and techniques used to improve our ability to safely identify and
      resect malignant lesions in patients with bladder cancer. RECENT FINDINGS:
      Enhanced endoscopic imaging technology may improve detection rates for bladder
      cancer throughout the upper and lower urinary tract, which may lead to
      improvements in recurrence and progression rates for non-muscle invasive bladder
      cancer (NMIBC). New techniques including narrow-band imaging (NBI), photodynamic
      diagnosis (PDD), Storz Professional Image Enhancement System (SPIES), optical
      coherence tomography (OCT), and others have shown benefit and may further improve
      our ability to detect and stage bladder tumors. Enhanced endoscopy technologies
      have already demonstrated value in improving the sensitivity of bladder cancer
      detection and early results suggest they may improve short- and long-term
      oncologic outcomes.

PMID- 30116988
TI  - Awareness and Attitudes of Nigerian Men Living in Abuja on Prostate Cancer and
      Screening.
AB  - Prostate cancer (PCa) is the most commonly diagnosed cancer among Nigerian men.
      The prevalence of PCa varies within Nigeria, with the highest prevalence of 1046
      per 100,000 in men over the age of 40 reported in Lagos. Unfortunately, 40% of
      these men are diagnosed with locally advanced disease and 35% with metastatic
      disease. Given the ability to screen for PCa among high-risk individuals, late
      stage diagnosis of PCa could be potentially reduced through education of men so
      that they seek screening. Along these lines, it is important to assess a
      population's knowledge and awareness on PCa and screening. Our study addresses
      this issue by evaluating awareness and attitudes of Nigerian men in Abuja on PCa
      and screening. Our results revealed gaps in awareness and perception of
      susceptibility to PCa and low levels of PCa screening. Factors such as age,
      education level, and income affected PCa awareness. In conclusion, our study
      points to the need to educate younger men of lower education and socioeconomic
      status in Nigeria with the aim to increase screening and earlier detection of
      PCa.

PMID- 30116989
TI  - The Effects of the Training Program and Counseling Program Given to Women Who
      Underwent a Mastectomy and Spouses.
AB  - Following breast cancer treatment, many families are negatively affected
      following the treatment for breast cancer of their women members. This study
      focused on assessing the effects of the training program and counseling program
      given to women who underwent a mastectomy and their spouses. Sixty women and 60
      spouses were recruited for this study. The women in the experimental group and
      their spouses were provided with a four-session training program, once a week.
      Following this training, a 3-month follow-up and counseling were given and an
      assessment made. There was significant difference between average post-test
      scores of spouses in the experimental and control groups, in terms of problem
      solving (p = .003), communication (p = .033), and roles (p = .000) dimensions of
      family assessment device (FAD). Noting that women in the experimental and control
      groups demonstrated significant differences among average post-test scores in
      terms of role emotional (p = .045) and mental health (p = .017) dimensions of
      Quality of Life Scale (SF-36), a significant difference existed among average
      post-test scores of spouses in the experimental and control groups in terms of
      general health (p = .017), role physical (p = .011), role emotional (p = .003),
      and mental health (p = .005) dimensions of Quality of Life Scale. These results
      indicated that training and counseling program provided to this population
      produced positive effects upon family functioning and quality of life.

PMID- 30116990
TI  - Intrapancreatic recurrence of intraductal tubulopapillary neoplasm (ITPN) 16
      years after the initial surgery for noninvasive ITPN: a case report.
AB  - BACKGROUND: Intraductal tubulopapillary neoplasm (ITPN) is a rare pancreatic
      intraductal neoplasm. It is characterized by a tubulopapillary growth pattern,
      entirely high-grade atypical cells, minimal cytoplasmic mucin, and no obvious
      luminal mucin secretion. Most of its biological nature remains unclear. CASE
      PRESENTATION: We herein report a case of intrapancreatic recurrence of ITPN in
      the remnant pancreas of a patient who underwent pancreatoduodenectomy 16 years
      previously for a noninvasive intraductal pancreatic head tumor. We reexamined the
      primary tumor and compared it with the most recently resected specimen.
      Histologically, the primary tumor showed a tubulopapillary growth of high-grade
      atypical cells with scanty cytoplasmic mucin, which was similar to the recently
      resected specimen except for the invasive area. Immunohistochemically, the
      neoplastic cells in both specimens showed focal staining of MUC1 and positivity
      for MUC6 but negativity for MUC2, MUC5AC, CDX2, and trypsin. Molecular analysis
      revealed no KRAS/GNAS/BRAF/PIK3CA mutations in either of the specimens.
      CONCLUSIONS: These findings of the original tumor and recently resected tumor
      were compatible with the features of ITPN. Thus, recurrence is possible even for
      a primary noninvasive ITPN, and long-term surveillance is recommended.

PMID- 30116991
TI  - Integration Process for Protein Extraction from Microalgae Using Liquid Biphasic
      Electric Flotation (LBEF) System.
AB  - Microalgae are the most promising sources of protein, which have high potential
      due to their high-value protein content. Conventional methods of protein
      harnessing required multiple steps, and they are generally complex, time
      consuming, and expensive. Currently, the study of integration methods for
      microalgae cell disruption and protein recovery process as a single-step process
      is attracting considerable interest. This study aims to investigate the novel
      approach of integration method of electrolysis and liquid biphasic flotation for
      protein extraction from wet biomass of Chlorella sorokiniana CY-1 and obtaining
      the optimal operating conditions for the protein extraction. The optimized
      conditions were found at 60% (v/v) of 1-propanol as top phase, 250 g/L of
      dipotassium hydrogen phosphate as bottom phase, crude microalgae loading of 0.1
      g, air flowrate of 150 cc/min, flotation time of 10 min, voltage of 20 V and
      electrode's tip touching the top phase of LBEF. The protein recovery and
      separation efficiency after optimization were 23.4106 +/- 1.2514% and 173.0870 +/
      4.4752%, respectively. Comparison for LBEF with and without the aid of electric
      supply was also conducted, and it was found that with the aid of electrolysis,
      the protein recovery and separation efficiency increased compared to the LBEF
      without electrolysis. This novel approach minimizes the steps for overall protein
      recovery from microalgae, time consumption, and cost of operation, which is
      beneficial in bioprocessing industry.

PMID- 30116992
TI  - The Economics and Regulation of PRP in the Evolving Field of Orthopedic
      Biologics.
AB  - PURPOSE OF REVIEW: This review provides an update on the current status of
      platelet-rich plasma (PRP). Topics covered include the current regulatory
      environment, economic outlook, and current clinical evidence. RECENT FINDINGS:
      The global PRP market is expected to grow to between 380 million and 4.5 billion
      (USD) over the next 5-10 years. The cost of a single treatment, which is not
      covered by most insurance, is roughly $500-$2500, with patients often returning
      for additional treatments. While PRP is not 'FDA-approved', it can be legally
      offered in the clinic 'off-label' in the USA for a myriad of musculoskeletal
      indications. Recently published meta-analyses have demonstrated statistically
      significant improvements that, in some cases, suggest that PRP may have
      clinically meaningful effects. However, given the fact that clearance is not
      synonymous with approval, PRP is a costly treatment not covered by insurance, and
      clinical trials have not demonstrated definitive efficacy, we recommend informing
      patients when providing PRP 'off-label'.

PMID- 30116993
TI  - Management of acute-on-chronic liver failure: an algorithmic approach.
AB  - Acute-on-chronic liver failure (ACLF) is a distinct syndrome of liver failure in
      a patient with chronic liver disease presenting with jaundice, coagulopathy and
      ascites and/or hepatic encephalopathy, developing following an acute hepatic
      insult and associated with high 28-day mortality. The definition though lacks
      global consensus, excludes patients with known distinct entities such as acute
      liver failure and those with end-stage liver disease. The initial Systemic
      Inflammatory Response Syndrome (SIRS) because of cytokine storm in relation to
      acute insult and/or subsequent development of sepsis due to immunoparalysis leads
      to extrahepatic organ failure. These cascades of events progress through a
      'Golden Window' period of about 7 days, subsequent to which majority of the
      patients develop complications, such as sepsis and extrahepatic organ failure.
      Prevention of sepsis, support of organs and management of organ failure (commonly
      hepatic, renal, cerebral, coagulation) and early referral for transplant is
      crucial. The APASL ACLF research consortium (AARC) liver failure score is a
      dynamic prognostic model for management decisions and is superior to existing
      models. Aggressive multidisciplinary approach can lead to a transplant-free
      survival in nearly half of the cases. The present review provides an algorithmic
      approach to management of organ failure, sepsis prevention, use of dynamic
      prognostic models for management decision and is aimed to improve the skills for
      managing and improving the outcomes of such critically ill patients.

PMID- 30116994
TI  - Drug-induced expression of EpCAM contributes to therapy resistance in esophageal
      adenocarcinoma.
AB  - BACKGROUND: With a less than 5% overall survival rate, esophageal adenocarcinoma
      (EAC) is one of the leading causes of death in the United States. Epithelial cell
      adhesion molecule (EpCAM) is a cancer stem cell (CSC) marker that is expressed in
      various epithelial carcinomas, including EAC. Accumulating evidence indicates
      that CSC subpopulations can initiate cancer development and, in addition, drive
      metastasis, recurrence and drug resistance. It has also been reported that EpCAM
      up-regulation in EAC may lead to an aggressive behavior and, thus, an adverse
      clinical outcome. Here, we aimed to determine whether treatment with standard
      chemotherapeutic agents may induce EpCAM expression and, concomitantly, increases
      in malignant potential and drug resistance in EAC. METHODS: EpCAM expression was
      assessed in 20 primary human EAC/adjacent normal tissues, as well as in a human
      EAC-derived cell line (OE-19), in a pre-malignant Barrett's Esophagus cell line
      (Bar-T) and in a benign esophageal cell line (HET 1-A), using
      immunohistochemistry, Western blotting and qRT-PCR, respectively. Drug-induced
      resistance was investigated in OE-19-derived spheres treated with (a combination
      of) adriamycin, cisplatin and 5-fluorouracil (ACF) using survival, adhesion and
      flow cytometric assays, respectively, and compared to drug resistance induced by
      standard chemotherapeutic agents (CTA). Finally, ACF treatment-surviving cells
      were evaluated for their tumor forming capacities both in vitro and in vivo using
      spheroid formation and xenograft assays, respectively. RESULTS: High EpCAM
      expression was observed in esophageal cancer tissues and esophageal cancer
      derived cell lines, but not in adjacent benign esophageal epithelia and benign
      esophageal cell lines (HET 1-A and Bar-T). The OE-19 cell spheres were drug
      resistant and EpCAM expression was significantly induced in the OE-19 cell
      spheres compared to the non-sphere OE-19 cells. When OE-19 cell spheres were
      challenged with ACF, the EpCAM mRNA and protein levels were further up-regulated
      up to 48 h, whereas a decreased EpCAM expression was observed at 72 h. EpCAM down
      regulation by RNA interference increased the ACF efficacy to kill OE-19 cells.
      Increased EpCAM expression coincided with the CSC marker CD90 and was associated
      with an aggressive growth pattern of OE-19 cell spheres in vivo. CONCLUSIONS:
      From our data we conclude that an ACF-induced increase in EpCAM expression
      reflects the selection of a CSC subpopulation that underlies tumor development
      and drug resistance in EAC.

PMID- 30116995
TI  - Isomeric effects tuning the electron transport in carotenoid derivatives: from
      ohmic to rectifier behavior.
AB  - Single-molecules have been widely investigated in the last decades due to their
      promises as devices in molecular electronics. One of the advantages in the use of
      natural compounds in molecular electronics is the economy of material and
      molecular synthesis, which makes the process both cheaper and self-sustaining.
      Although many studies have considered electronic transport in single molecules,
      there are few studies associated with isomeric effects in biologically appealing
      systems. In the present work, we have studied ballistic electron transport in two
      isomeric forms of a retinol molecule: 11-cis and all-trans-retinol. The molecules
      were connected between two Au(111) electrodes and calculations were performed
      with the NEGF-DFT methodology. Current-voltage, differential conductance, and
      rectification curves were obtained and compared for two structures. While 11-cis
      retinol shows a more symmetrical current-voltage curve, all-trans-retinol acts as
      molecular diode for low applied voltages. Our results suggest that a simple
      isomeric effect modulates the molecular device from nanowires to diodes with
      potential applications as field-effect transistors.

PMID- 30116996
TI  - Fatal Attraction: Ricinus communis Provides an Attractive but Risky Mating Site
      for Holotrichia parallela Beetles.
AB  - The castor bean, Ricinus communis L., is a non-host plant for the large black
      chafer, Holotrichia parallela Motschulsky (Coleoptera: Scarabaeidae). In
      laboratory bioassays we found that this plant was no less attractive than the
      main host plant (peanut, Arachis hypogaea) and three food plant species:
      velvetleaf (Abutilon theophrasti), the glossy privet (Ligustrum lucidum), and the
      Siberian elm (Ulmus pumila). In field trapping experiments a Soxhlet extract of
      castor bean leaves caught more beetles than the optimal sex lure blend [(R)-(-)
      linalool and (L)-isoleucine methyl ester blended in a ratio of 1:4], compared at
      equal doses (500 MUl), and laboratory bioassays indicated that a castor bean
      plant could enhance the attractiveness of different blend ratios of sex lures.
      Olfactometer bioassays showed that males prefer volatiles emitted from different
      combinations of castor bean plant extracts and a signaling female over a female
      alone. In the presence of castor bean plants copulation rates of H. parallela
      were highest among all test environments both in laboratory bioassays (60%) and
      in field tests (70%). This study, combined with our previous observation of the
      feeding behavior of H. parallela adults on castor bean leaves, suggests that
      castor bean plants may provide an attractive but risky mating site for H.
      parallela beetles. The enhancement of male mate-location and copulation rate in
      the presence of castor bean plants can balance its paralytic effects on H.
      parallela after intake of potential toxins contained in its leaves.

PMID- 30116997
TI  - Adjuvant Pharmacotherapies to Insulin for the Treatment of Type 1 Diabetes.
AB  - PURPOSE OF REVIEW: Insulin therapy alone fails to achieve target glycemic control
      in the majority of individuals with type 1 diabetes (T1D), motivating the
      investigation of additive medications. This review focuses on the recent findings
      on the use of adjunctive pharmacotherapy in T1D. RECENT FINDINGS: Metformin and
      glucagon-like peptide-1 receptor agonists have been associated with weight
      reduction and decrease in daily insulin requirements without sustainable
      improvement in glycemic control. Sodium-glucose cotransporter (SGLT)-2
      inhibitors, dual SGLT-1/2 inhibitors, and pramlintide have been shown to reduce
      hemoglobin A1c, induce weight loss, and lower insulin dose. The benefits of
      dipeptidyl peptidase-4 inhibitors, thiazolidinediones, and alpha glucosidase
      inhibitors appear to be more limited. Gastrointestinal symptoms and increased
      hypoglycemia are adverse effects of certain classes. Although not devoid of side
      effects, additive pharmacotherapies in T1D can improve glycemic control and lower
      body weight and insulin requirement. Longer studies are needed before
      consideration for widespread clinical care.

PMID- 30116998
TI  - Microplastics in Seafood and the Implications for Human Health.
AB  - PURPOSE OF REVIEW: We describe evidence regarding human exposure to microplastics
      via seafood and discuss potential health effects. RECENT FINDINGS: Shellfish and
      other animals consumed whole pose particular concern for human exposure. If there
      is toxicity, it is likely dependent on dose, polymer type, size, surface
      chemistry, and hydrophobicity. Human activity has led to microplastic
      contamination throughout the marine environment. As a result of widespread
      contamination, microplastics are ingested by many species of wildlife including
      fish and shellfish. Because microplastics are associated with chemicals from
      manufacturing and that sorb from the surrounding environment, there is concern
      regarding physical and chemical toxicity. Evidence regarding microplastic
      toxicity and epidemiology is emerging. We characterize current knowledge and
      highlight gaps. We also recommend mitigation and adaptation strategies targeting
      the life cycle of microplastics and recommend future research to assess impacts
      of microplastics on humans. Addressing these research gaps is a critical priority
      due to the nutritional importance of seafood consumption.

PMID- 30116999
TI  - Caribou (Rangifer tarandus) and Inuit Nutrition Security in Canada.
AB  - Caribou (Rangifer tarandus) has been fundamental to the diet and culture of
      Arctic Indigenous Peoples for thousands of years. Although caribou populations
      observe natural cycles of abundance and scarcity, several caribou herds across
      the Circumpolar North have experienced dramatic declines in recent decades due to
      a range of interrelated factors. Broadly, the objectives of this study are to
      examine food and nutrition security in relation to wildlife population and
      management status across Inuit Nunangat (the Inuit homeland, consisting of four
      regions across the Canadian Arctic). Specifically, we: (1) characterize the
      contribution of caribou to Inuit nutrition across northern Canada and (2)
      evaluate the population and management status of caribou herds/populations
      harvested by Inuit. Dietary data were derived from the 2007-2008 Inuit Health
      Survey, which included dietary information for Inuit adults (n = 2097) residing
      in thirty-six communities, spanning three regions (the Inuvialuit Settlement
      Region, Nunavut, and Nunatsiavut) of the Canadian North. Published information
      regarding the range, abundance, status, and management status of caribou
      herds/populations was collected through document analysis and was validated
      through consultation with northern wildlife experts (territorial governments, co
      management, and/or Inuit organizations). While caribou contributed modestly to
      total diet energy (3-11% of intake) across the regions, it was the primary source
      of iron (14-37%), zinc (18-41%), copper (12-39%), riboflavin (15-39%), and
      vitamin B12 (27-52%), as well as a top source of protein (13-35%). Restrictions
      on Inuit subsistence harvest (harvest quotas or bans) are currently enacted on at
      least six northern caribou herds/populations with potential consequences for
      country food access for over twenty-five Inuit communities across Canada. A
      holistic multi-sectorial approach is needed to ensure the sustainability of
      wildlife populations, while supporting Inuit food and nutrition security in the
      interim.

PMID- 30117000
TI  - Detection and Molecular Characterization of Yellow Fever Virus, 2017, Brazil.
AB  - At the end of 2016, Brazil experienced an unprecedented yellow fever (YF)
      outbreak. Clinical, molecular and ecological aspects of human and non-human
      primate (NHP) samples collected at the beginning of the outbreak are described in
      this study. Spatial distribution analyses demonstrated a strong overlap between
      human and NHP cases. Through molecular analyses, we showed that the outbreak had
      a sylvatic origin, caused by the South American genotype 1 YFV, which has already
      been shown to circulate in Brazil. As expected, the clusters of cases were
      identified in regions with a low vaccination coverage. Our findings highlight the
      importance of the synchronization of animal surveillance and health services to
      identify emerging YF cases, thereby promoting a better response to the vulnerable
      population.

PMID- 30117001
TI  - Surveillance of Arboviruses in Primates and Sloths in the Atlantic Forest, Bahia,
      Brazil.
AB  - From 2006 through 2014, we conducted seroepidemiological surveys on non-human
      primates and sloths to investigate the possible circulation of arboviruses in
      Bahia Atlantic Forest, Brazil. We collected a total of 196 samples from 103
      Leontopithecus chrysomelas, 7 Sapajus xanthosternos, 22 Bradypus torquatus and 7
      Bradypus variegatus. Serum samples were tested using neutralization test and
      hemagglutination inhibition test to detect total antibodies against 26 different
      arboviruses. The overall prevalence of arboviruses was 36.6% (51/139), with the
      genus Flavivirus having the highest prevalence (33.1%; 46/139), followed by
      Phlebovirus (5.0%; 7/139), Orthobunyavirus (4.3%; 6/139) and Alphavirus (0.7%;
      1/139). Monotypic reactions suggest that the wild animals were exposed naturally
      to at least twelve arboviruses. Added results from the neutralization test,
      animals were exposed to thirteen arboviruses. Most of these viruses are
      maintained in transmission cycles independent of human hosts, although antibodies
      against dengue virus serotypes 1, 2 and 3 were found in this study. To our
      knowledge, this is the first study reporting exposure to arboviruses in L.
      chrysomelas, S. xanthosternos and B. torquatus. Our results also highlight that
      the Southern Bahia Atlantic Forest has a variety of vertebrate hosts and
      potential vectors, which may support the emergence or re-emergence of
      arboviruses, including those pathogenic to humans.

PMID- 30117002
TI  - The Use of Neopterin as a Noninvasive Marker in Monitoring Diseases in Wild
      Chimpanzees.
AB  - Pathogen analysis in wild great apes is both time- and resource-consuming.
      Therefore, we examined the potential use of urinary neopterin, a sensitive marker
      of cell-mediated immune system activation, as a disease marker and unspecific
      screening tool to facilitate informed pathogen analysis in great ape health
      monitoring. To test this, urinary neopterin was correlated to other disease
      markers such as sickness behaviors, fever, and urine parameters. Seasonal
      variation in urinary neopterin levels was investigated as well. The study
      encompassed noninvasively collected longitudinal data of young wild chimpanzees
      from the Tai National Park, Cote d'Ivoire. Relationships between disease markers
      were examined using a linear mixed model and a case study approach. Seasonal
      variation in urinary neopterin was tested using a linear mixed model. While the
      linear mixed model found no obvious relationship between urinary neopterin levels
      and other disease markers, the case study approach revealed a pattern resembling
      those found in humans. Urinary neopterin levels indicated seasonal immune system
      activation peaking in times of low ambient temperatures. We suggest the use of
      urinary neopterin as an unspecific screening tool in great ape health monitoring
      to identify relevant samples, individuals, and time periods for selective
      pathogen analysis and zoonotic risk assessment.

PMID- 30117003
TI  - Fairly rare clear cell adenocarcinoma mimicking liver cancer: a case report.
AB  - BACKGROUND: Clear cell carcinoma commonly occurs in the ovary and kidney, and
      clear cell cholangiocarcinoma was rarely reported. Differential diagnosis which
      the origin of the tumor located on the liver surface is intrahepatic or
      extrahepatic was difficult. Herein, we report a case of clear cell adenocarcinoma
      mimicking liver cancer. CASE PRESENTATION: This was a 55-year-old female who had
      the tumor with cystic component in the liver. She was performed hepatectomy and
      diagnosed as clear cell adenocarcinoma. Histopathological evaluation revealed
      intra-cystic clear cell adenocarcinoma. The tumor has ductal structure including
      mucin and atypical nuclear with clear cytoplasm. The tumor was separated from the
      liver and the diaphragm. The expression of Pax8 was positive, but the expression
      CK7 and HNF1beta was positive and that of CD10 and ER was negative, which
      indicate that the tumor has the feature of clear cell carcinoma of ovary, not
      renal cell carcinoma nor cholangiocarcinoma. CONCLUSIONS: Our experience with
      this patient suggests that this tumor may originate from the endometriosis onto
      the diaphragm from the detailed results of immunohistochemical staining.

PMID- 30117005
TI  - Barriers and Facilitators to Breast and Cervical Cancer Screening Among
      Immigrants in the United States.
AB  - To summarize the literature on barriers and facilitators to breast and cervical
      cancer screening among immigrants to the US. A literature review was conducted
      for studies on breast and cervical cancer screening among immigrant populations.
      A thematic analysis of 180 studies identified a variety of barriers and
      facilitators to screening at the personal and system levels. Personal barriers
      included lack of knowledge and insurance coverage, high cost of care, and
      immigration status. System barriers included poor access to services, lack of
      interpreter services, and insensitivity to patient needs. Facilitators to
      screening included knowledge of disease, access to information sources, physician
      recommendation, and social networks. Cultural norms and resource availability at
      the individual and system levels influence screening among immigrants. Health
      insurance coverage was found to be an important predictor of preventative
      screening use. Future research should seek to identify the best way to address
      this and other barriers to cancer screening among immigrants groups.

PMID- 30117006
TI  - Preface.

PMID- 30117004
TI  - Infective Endocarditis: Update on Epidemiology, Outcomes, and Management.
AB  - PURPOSE OF REVIEW: Infective endocarditis remains a highly mortal disease, yet
      the diagnosis often is missed or made only late in the disease course. The
      spectrum of patients presenting with endocarditis is shifting with different risk
      factors, predisposing patient characteristics, and treatment recommendations than
      in the past. This review addresses changes in the epidemiology of infective
      endocarditis, along with current diagnostic imaging modalities, treatment
      recommendations, and mortality trends. RECENT FINDINGS: Risk factors for
      endocarditis now include the growing population of adults with congenital heart
      disease and patients with frequent healthcare contact for other comorbidities, as
      well as patients who are hemodialysed and immunocompromised or use intravenous
      drugs. Although transthoracic and transesophageal echocardiography are essential
      for diagnosis, additional testing (nuclear, computed tomographic, and magnetic
      resonance imaging) is helpful in selected patients. Early surgical management,
      even in high-risk patients, has a mortality benefit because eradication of
      infection with antibiotics alone is difficult and because valve destruction often
      results in hemodynamic compromise. As part of a broad differential diagnosis,
      clinicians should consider the diagnosis of endocarditis in patients with risk
      factors, even when the clinical presentation is nonspecific. Blood cultures and
      echocardiography are the first steps for diagnosis. Other imaging modalities can
      enhance diagnosis, particularly in patients with intracardiac devices or
      prosthetic material. Evidence from observational studies support early surgical
      intervention to reduce morbidity and mortality from this lethal condition.

PMID- 30117008
TI  - (Un)bridgeable Chasms?: Doctor-Patient Interactions in Select Graphic Medical
      Narratives.
AB  - Effective doctor patient relationships are predicated on doctors' relational
      engagement and affective/holistic communication with the patients. On the
      contrary, the contemporary healthcare and patient-clinician communication are at
      odds with the desirable professional goals, often resulting in dehumanization and
      demoralization of patients. Besides denigrating the moral agency of a patient
      such apathetic interactions and unprofessional approach also affect the treatment
      and well-being of the sufferer. Foregrounding multifaceted doctor-patient
      relationships, graphic pathographies are a significant cultural resource which
      recreate the embodied moment of clinical encounters as they also lay bare
      qualitative tensions between patient' illness experience with doctor's
      professional understanding of the same. Taking these cues, the present article
      drawing theoretical postulates of Rita Charon, Deborah Lupton, and Havi Carel
      close reads Peter Dunlap-Shohl's My Degeneration: A Journey Through Parkinson's
      (2015), Brian Fies' Mom's Cancer (2006), and Stan Mack's Janet & Me: An
      Illustrated Story of Love and Loss (2004) to investigate the nature of doctor
      patient relationship vis-a-vis communication and the implications of bad
      doctoring/communicative practices on patient identity and emotions. Furthermore,
      the article also examines the aesthetic and functional role of comics in bringing
      into relief the graphically mediated doctor-patient relationship.

PMID- 30117007
TI  - Revision total knee arthroplasty: hybrid vs standard cemented fixation.
AB  - INTRODUCTION: Modular systems with stems are necessary for the stability of
      revision total knee arthroplasty (rTKA), but controversy remains as to the best
      fixation method: cemented or hybrid (noncemented stem). The aim of this study was
      to assess the clinical, X-ray, life-quality and survival results obtained with
      each fixation method. MATERIALS AND METHODS: During the period 2000-2013, rTKA
      was performed on 67 patients (29 cemented arthroplasty and 38 hybrid fixation).
      The average follow-up was 7 years (range 2-15). All patients were evaluated
      clinically and radiographically using the American Knee Society Score (AKSS), the
      Western Ontario and McMaster Universities Arthritis Index (WOMAC), and the Short
      Form Health Survey (SF-36). A survival study was performed via Kaplan-Meier
      analysis. RESULTS: There were no differences between the cemented and hybrid
      fixation groups in the preoperative and postoperative AKSS clinical evaluation
      indices and the SF-36 health index. However, the WOMAC assessment scale did
      reveal statistically significant differences between the groups, with a global
      classification of 64.9 points weighted at 100 (SD 16.8) for cemented fixation
      versus 78.9 (SD 9.0) for hybrid fixation (p = 0.001). The corresponding values
      for stiffness were 61.6 (SD 12.9) and 80.5 (SD 14.7) (p = 0.001), and those for
      function were 61.3 (SD 19.4) and 78.1 (SD 10.5) (p = 0.001). No significant
      differences between the groups were recorded with respect to the pain score (p =
      0.4) or the results of the Kaplan-Meier survival analysis. CONCLUSION: Although
      the results were similar for the two groups, hybrid fixation tended to produce
      better results than cemented fixation. In view of the risk of further loosening,
      we prefer the more conservative approach, i.e. hybrid fixation. LEVEL EVIDENCE:
      Level III.

PMID- 30117009
TI  - Microstructure of osteophytes in medial knee osteoarthritis.
AB  - Knee osteoarthritis (OA) is one of the most common musculoskeletal diseases and
      osteophytes area frequent radiographic feature of knee OA. The osteophyte
      structure in knee OA, however, is not well elucidated. This study aimed to
      clarify the three-dimensional microstructural characteristics of osteophytes in
      the medial compartment of the knee in knee OA patients using micro-computed
      tomography (micro-CT). We hypothesized that the morphology of osteophytes would
      differ from that of the neighboring normal cancellous bones. Ten medial
      compartment knee OA patients with Kellgren-Lawrence grade 4 severity were
      enrolled in the study, and all patients underwent total knee arthroplasty.
      Osteophytes and cancellous bones were obtained from the medial femoral condyle.
      The three-dimensional trabecular bone microstructure was analyzed by quantitative
      micro-CT using image analysis software. The trabecular bone volume fraction and
      trabecular number were significantly lower in osteophytes than in cancellous
      bones. Consistently, trabecular separation was significantly higher in
      osteophytes. Osteophytes exhibited disorganized trabecular orientation,
      trabecular perforation, disruption, and complete disconnection. These findings
      suggest that osteophytes are functionally fragile.

PMID- 30117010
TI  - Financing graduate medical education: challenges for training the next generation
      of electrophysiologists.
AB  - The system for graduate medical education (GME) in the USA is vital to
      maintaining a well-trained physician population to meet the needs of the nation.
      The funding of this system over the last several decades has been complicated,
      and the government's role in funding GME is controversial. In this paper, the
      current mechanisms for funding residency and fellowship training are outlined as
      well as proposed changes to system. The current system has made funding
      electrophysiology training difficult, and the proposed changes have profound
      implications. It is important for the electrophysiology community to be educated
      and advocate for electrophysiology fellowship training such that Americans
      continue to have appropriate access to arrhythmia care.

PMID- 30117011
TI  - Total laser cycles-a measure of transvenous lead extraction difficulty.
AB  - BACKGROUND: Several variables have been identified as predictors for difficult or
      complicated transvenous lead extraction (TLE), including age and number of
      implanted leads, as well as patient's age; however, a standard measure of TLE
      difficulty has not been described. OBJECTIVE: Total laser cycles (TLCs) delivered
      during laser-assisted TLE is an objective variable that could reflect the
      difficulty of TLE. This study investigated whether TLC is correlated with known
      predictors of difficult TLE. METHODS: In a retrospective study of TLE procedures
      using the laser sheath, we analyzed TLC delivered and compared it to established
      predictors of procedural failure and complications. RESULTS: Of 166 patients
      undergoing TLE, the laser sheath (SLS II or Glidelight, Spectranetics Inc.,) was
      used as the primary extraction sheath in 130 patients, and 100 patients had
      complete TLC data available. The mean age of the oldest lead (AOL) was 7.1 +/-
      3.2 years with a median of 6.91 (interquartile range [IQR] 0.48-16.69) years, and
      1.6 +/- 0.7 leads (range, 1-4) were extracted per procedure. Two thirds of
      procedures involved ICD leads. Clinical success was 99%, with one patient (1%)
      experiencing a major complication. Median TLC delivered was 1165 (IQR, 567-2062;
      range, 49-9522). TLC was positively correlated with AOL (r = 0.227, p = 0.023),
      and the combined age of leads was extracted (r = 0.307, p = 0.002). TLC was also
      positively correlated with number of leads extracted per procedure (rho = 0.227,
      p = 0.024). There was a non-significant negative trend towards correlation
      between TLC and patient's age (r = -0.112, p = 0.268). CONCLUSION: TLC showed
      significant correlation with known predictors of difficulty during TLE using the
      laser sheath. TLC is an objective method to report the difficulty of TLE and
      could usefully be reported in future series of laser lead extractions.

PMID- 30117012
TI  - Impact of land cover types on soil aggregate stability and erodibility.
AB  - Gokceada is the biggest island, and it is also known as the organic island of
      Turkey. Approximately 65% of the Gokceada lands have slope > 12%. Climate,
      topography, land cover, and soil characteristics are considered to be the main
      natural factors affecting soil erosion severity in the Gokceada. Prevention of
      soil degradation, hence the preservation or improvement of the overall quality of
      the soil, is directly related to the presence of stable soil aggregates. In
      addition, the resistance to weathering and replacement of soil particles are also
      relevant aspects in terms of sustainability. Aggregate stability (AS) and
      erodibility of land (Kfac) are related to soil properties. However, this
      relationship can vary under different circumstances. In this study, 248 surface
      soil samples have been taken from forest and semi-natural areas (FSNA) and
      agricultural areas (AGRA) according to CORINE 2006. Eleven selected soil
      properties were measured, and their impacts on AS and Kfac (RUSLE-K) were
      determined by using the CRT (classification and regression tree) in Gokceada.
      Results showed that the relations among soil characteristics changed according to
      the land cover classes. Total organic carbon is much more associated with AS in
      AGRA, while total carbon is associated with AS in FSNA. The effect of calcium
      carbonate on Kfac was higher than other soil properties when the land cover type
      was ignored. On the other hand, in AGRA, the effect of between clay content on
      Kfac was greater than those of FSNA.

PMID- 30117013
TI  - Predictors of bone fractures in a single-centre cohort of hemodialysis patients:
      a 2-year follow-up study.
AB  - PURPOSE: Bone involvement represents one of the complications of end-stage
      chronic kidney disease, with fractures being its major risk. The aim of our study
      was to assess the frequency and predictors of low-trauma fractures in a cohort of
      maintenance hemodialysis patients followed-up on for 2 years. METHODS: 59
      patients (67.6 +/- 13.1 years, 43 males) treated with hemodiafiltration underwent
      initially laboratory (markers of calcium-phosphate metabolism and bone turnover
      markers) and densitometry examination with TBS assessment (Lunar Prodigy, TBS
      software 2.1.2). During 24-month follow-up, the frequency of low-trauma fractures
      was assessed and possible predictors of increased fracture risk were identified
      using product-moment correlation matrices. RESULTS: Altogether 7 (11.9%) low
      trauma fractures were observed. In the whole group, age (P = 0.047), T-score in
      proximal femur (P = 0.04), low vitamin D, low BMI (P = 0.03 for both), and higher
      FRAX for major osteoporotic fracture (P = 0.01) were connected with fractures,
      but in multi-variate analysis only BMI remained significantly negatively
      associated with fractures (P = 0.047). TBS and bone turnover markers failed to
      predict fractures. However, women with fractures had significantly lower serum
      phosphate (P = 0.03) and higher parathyroid hormone (P = 0.04). Parameters of hip
      structure analysis significantly correlated with FRAX, but not with fractures.
      CONCLUSIONS: In a group of hemodialysis patients from one centre, T-score in
      proximal femur, low vitamin D, low BMI, and high FRAX for major osteoporotic
      fracture were associated with low-trauma fractures, however, in multi-variate
      analysis only low BMI remained a significant predictor of fracture risk.

PMID- 30117014
TI  - Are there any metastases to the chest in non-muscle-invasive bladder cancer
      patients on follow-up computed tomography?
AB  - PURPOSE: The purpose of the study was to retrospectively determine whether there
      are metastases to the chest in patients with primary non-muscle-invasive
      urothelial carcinoma in the bladder on the follow-up computed tomography (CT).
      METHODS: We analyzed 328 patients with follow-up chest CT for urothelial
      carcinoma of the bladder diagnosed between January 2004 and September 2013. We
      divided patients into four groups: Ta (n = 74), T1 (n = 78), carcinoma in situ
      (CIS, n = 25), and >= T2 (n = 151). We used the chest CT to determine whether
      there were positive findings of metastasis. Univariate and multivariate analyses
      were achieved using categories of T stage, histological grade, multifocal
      lesions, and recurrence. RESULTS: On univariate analysis, there were significant
      differences on T stage (p < 0.001) and histological grade (p = 0.001), and there
      was no significant difference on multifocal lesions (p = 0.11) and recurrence (p
      = 0.34). Positive findings of metastases were observed in 1.4% (1/74) of the Ta
      patients, 0% (0/78) of the T1 patients, 8.0% (2/25) of the patients with
      carcinoma in situ (CIS), and 27.2% (41/151) of the >= T2 patients (p < 0.001). On
      multivariate analysis, T staging was independent variable for positive findings
      of metastasis (Odds ratio; 2.84, 95% Confidence Interval; 1.65-4.89). In
      contrast, histological grade, multifocal lesions, and recurrence were not
      independent variables. CONCLUSIONS: T stage would affect to metastasis to the
      chest. It might be appropriate to omit chest CT in patients with Ta or T1 without
      upstaging in the course of follow-up. We may suggest that the follow-up chest CT
      in patients with CIS.

PMID- 30117015
TI  - PAX2 may induce ADAM10 expression in renal tubular epithelial cells and
      contribute to epithelial-to-mesenchymal transition.
AB  - PURPOSE: We sought to investigate the role of PAX2 in renal epithelial-to
      mesenchymal transition (EMT), examining the influence of PAX2 on ADAM10
      expression during renal EMT and ADAM10 expression in fibrotic kidneys. METHODS: A
      rat renal tubular epithelial cell line, NRK52E, was transfected with lentivirus
      carrying PAX2, and E-cadherin and alpha-SMA expressions were measured. The
      influence of PAX2 on ADAM10 promoter activity was evaluated using chromatin
      immunoprecipitation (CHIP) and dual-luciferase reporter assay. We also treated
      NRK52E with ADAM10-specific over-expression vector and inhibitors and measured E
      cadherin and alpha-SMA expression. In vivo, Wistar rats (n = 36) were subjected
      to unilateral ureteral obstruction (UUO) (n = 18) or sham surgery (n = 18), with
      tissues from post-operative day 3, 7, and 14 days examined, and PAX2/ADAM10
      activity measured. ADAM10 expression was also assessed in kidneys from patients
      with chronic kidney disease (CKD). RESULTS: In NRK52E overexpressing PAX2, ADAM10
      and alpha-SMA levels were increased, while E-cadherin levels were decreased. CHIP
      and dual-luciferase reporter assay showed that PAX2 directly bound to a specific
      site within the ADAM10 promoter, and over-expression of PAX2 significantly
      activated ADAM10 transcription. NRK52E with ADAM10 over-expression also
      significantly decreased E-cadherin and increased alpha-SMA levels. In the
      fibrotic kidneys of rats with UUO, E-cadherin levels were increased and alpha-SMA
      levels were decreased, and expression of PAX2 and ADAM10 increased. ADAM10
      expression also elevated in the renal tissues of CKD patients. CONCLUSIONS: PAX2
      directly increased expression of ADAM10, the presence of which contributed to EMT
      in renal tubular epithelia and hence plays an important role in renal fibrosis.

PMID- 30117017
TI  - Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor.
AB  - Ixazomib, the first oral proteasome inhibitor, is approved in combination with
      lenalidomide and dexamethasone for the treatment of patients with multiple
      myeloma (MM) who have received at least one prior therapy. Ixazomib is a
      selective, potent, and reversible inhibitor of the 20S proteasome, and
      preferentially binds to and inhibits the beta5 chymotrypsin-like proteolytic
      site. Ixazomib absorption is rapid, with a median time to reach maximum plasma
      concentration of approximately 1 h post-dose. Ixazomib pharmacokinetics (PK) are
      adequately described by a three-compartment model (terminal half-life of 9.5
      days) with first-order linear absorption (oral bioavailability of 58%). Plasma
      exposures of ixazomib increase in a dose-proportional manner. A high-fat meal
      decreases both the rate and extent of ixazomib absorption, supporting
      administration on an empty stomach. Population PK analyses demonstrated that no
      dose adjustment is required based on age, body size/weight, race, sex, mild-to
      moderate renal impairment, or mild hepatic impairment. Results from dedicated
      studies indicate that a reduced starting dose (from 4 to 3 mg) is appropriate for
      patients with severe renal impairment, end-stage renal disease requiring
      dialysis, or moderate-to-severe hepatic impairment. Non-cytochrome P450 (CYP)
      mediated metabolism appears to be the major clearance mechanism for ixazomib.
      Drug-drug interaction studies have shown no meaningful effects of strong
      inhibitors of CYP3A on ixazomib PK; however, the strong inducer rifampin caused a
      clinically relevant reduction in ixazomib exposure, supporting the recommendation
      to avoid concomitant administration of ixazomib with strong CYP3A inducers.
      Exposure-response analyses of data from the phase III TOURMALINE-MM1
      registrational study demonstrate a favorable benefit-risk profile for the
      approved dose and regimen of weekly ixazomib 4 mg on days 1, 8, and 15 of each 28
      day cycle.

PMID- 30117016
TI  - miR-129-5p inhibits gemcitabine resistance and promotes cell apoptosis of bladder
      cancer cells by targeting Wnt5a.
AB  - OBJECTIVES: Gemcitabine resistance is a major obstacle for effective treatment of
      bladder cancer. This study was aimed to investigate the potential role of miR-129
      5p in the development of gemcitabine resistance in bladder cancer cells and its
      underlying mechanism. METHODS: The IC50 for gemcitabine in 20 bladder cancer
      cells was first profiled from Genomics of Drug Sensitivity in Cancer. miR-129-5p
      level and gene mRNA expression were detected using quantitative real-time PCR
      (qRT-PCR). Cell viability, apoptosis, and gene protein level were assessed by
      MTT, flow cytometry, and Western blot, respectively. Regulatory relationship
      between Wnt5a and miR-129-5p was determined using luciferase reporter assay.
      RESULTS: We found that down-regulated miR-129-5p level contributed to gemcitabine
      resistance in bladder cancer cells and tissues. We also observed restoration of
      miR-129-5p could significantly increase cell sensitivity to gemcitabine and
      promote cell apoptosis. Mechanism analysis revealed that Wnt5a is a direct target
      gene of miR-129-5p and knock-down of Wnt5a reversed gemcitabine resistance.
      CONCLUSIONS: Taken together, our findings indicate that miR-129-5p and Wnt5a may
      be novel therapeutic targets for overcoming gemcitabine resistance in bladder
      cancer treatment.

PMID- 30117018
TI  - Enthesitis and Dactylitis in Psoriatic Disease: A Guide for Dermatologists.
AB  - Psoriatic arthritis (PsA) is an inflammatory arthritis that is estimated to
      affect approximately 30% of patients with psoriasis. Enthesitis and dactylitis,
      two hallmarks of PsA, are associated with radiographic peripheral/axial joint
      damage and severe disease. Clinical symptoms of enthesitis include tenderness,
      soreness, and pain at entheses on palpation, whereas dactylitis is recognized by
      swelling of an entire digit that is different from adjacent digits. Both
      ultrasound and magnetic resonance imaging can be used to diagnose enthesitis and
      dactylitis, especially in patients in whom symptoms may be difficult to discern.
      Delayed treatment of PsA can result in irreversible joint damage and reduced
      quality of life. Thus, it is recommended that dermatologists monitor patients
      with psoriasis for these two early and important manifestations of PsA.

PMID- 30117020
TI  - Danoprevir: First Global Approval.
AB  - Ascletis has developed danoprevir (Ganovo(r)), an orally-administered hepatitis C
      virus NS3 protease inhibitor, as a treatment for hepatitis C. Based on positive
      results in phase II and phase III trials in patients with hepatitis C,
      danoprevir, in combination with ritonavir, peginterferon alfa and ribavirin was
      recently approved for marketing in China for the treatment of treatment-naive
      patients with non-cirrhotic genotype 1b chronic hepatitis C. This article
      summarizes the milestones in the development of danoprevir leading to this first
      approval.

PMID- 30117021
TI  - Encorafenib and Binimetinib: First Global Approvals.
AB  - Encorafenib (BraftoviTM), a BRAF inhibitor, and binimetinib (Mektovi(r)), a MEK
      inhibitor, are two orally bioavailable drugs developed by Array BioPharma. In
      June 2018 they each received their first global approval, in the USA, for use in
      combination, for patients with unresectable or metastatic melanoma with a
      BRAFV600E or -V600K mutation as detected by an FDA-approved test. Registration
      applications for encorafenib and binimetinib for use in combination in the
      treatment of BRAF-mutation-positive advanced melanoma have also been submitted in
      the EU, Australia, Switzerland and Japan, with the EMA Committee for Medicinal
      Products for Human Use adopting a positive opinion in July 2018 towards granting
      the drugs marketing authorizations in the EU. Encorafenib plus binimetinib
      combination therapy is also in ongoing phase III clinical development in the
      treatment of metastatic colorectal cancer. This article summarizes the milestones
      in the development of encorafenib and binimetinib leading to these first
      approvals for the treatment of BRAFV600E or -V600K-mutation-positive unresectable
      or metastatic melanoma.

PMID- 30117023
TI  - Clinical, neuroimaging and histopathological features of gliomatosis cerebri: a
      systematic review based on synthesis of published individual patient data.
AB  - INTRODUCTION: Gliomatosis cerebri (GC) is a rare fatal widespread infiltrating
      CNS tumor. As consistent disease features have not been established, the tumor
      comprises a diagnostic challenge. METHODS: We conducted a systematic literature
      search for published case reports and case series on patients with histologically
      confirmed GC. Clinical, diagnostic, neuroimaging, histopathological, and
      molecular data on individual or summary patient level were extracted and
      analyzed. RESULTS: A total of 274 studies were identified, including 866 patients
      with individual-level data and 782 patients with summary data (58.9% males, mean
      age 43.6 years). Seizures (49.8%) were the most common presenting symptom
      followed by headache (35.9%), cognitive decline (32.2%), and focal motor deficits
      (32%). Imaging studies showed bilateral hemisphere involvement in 65%,
      infratentorial infiltration in 29.9% and a focal contrast-enhanced mass (type II
      GC) in 31.1% of cases. MRI (extensive hyperintensities in T2/FLAIR sequences) and
      MR spectroscopy (elevated choline, creatinine, and myoinositol levels; decreased
      NAA levels) showed highly consistent findings across GC patients. Low-grade and
      anaplastic astrocytoma were the most prevalent diagnostic categories, albeit
      features of any histology (astrocytic, oligodendroglial, oligoastrocytic) and
      grade (II-IV) were also reported. Among molecular aberrations, IDH1 mutation and
      MGMT promoter methylation were the most commonly reported. Increasing time
      elapsed from symptom onset to diagnosis comprised the only independent
      determinant of the extent of CNS infiltration. CONCLUSION: A distinct clinical,
      neuroimaging, histopathological, or molecular GC phenotype is not supported by
      current evidence. MRI and MR spectroscopy are important tools for the diagnosis
      of the tumor before confirmation with biopsy.

PMID- 30117024
TI  - Photodegradation using TiO2-activated borosilicate tubes.
AB  - This study examines the photocatalytic activity of titanium dioxide (TiO2)
      semiconductor supported on borosilicate tubes (cut-off 290 nm) towards removal of
      a mix of persistent organic pollutants (POPs) from water. For this purpose, two
      widely used analgesic and anti-inflammatory drugs (NSAIDs), ibuprofen (IBU) and
      mefenamic acid, along with MCPA sodium monohydrate, which is a common herbicide
      frequently used in the agricultural activities, were selected as a case study.
      Borosilicate tubes were coated with titanium oxide through two different
      approaches: sol-gel dip-coating and a hybrid nanoparticle dip-coating and plasma
      enhanced chemical vapour deposition (PECVD) process. The photochemical reactor
      that hosts the titania-coated tubes was designed to permit continuous throughput
      of liquid feed stream. The photodegradation experiments were performed in
      laboratory conditions under artificial irradiation simulating solar light. The
      efficiency of direct photolysis and heterogeneous photocatalysis (TiO2) was
      investigated, and the performance of each coating method was evaluated. Kinetic
      studies for each experiment were accomplished, the overall results showed poor
      efficiency and insufficient removal for NSAIDs through direct photolysis, whereas
      applying heterogeneous photacatalysis with TiO2 coated on borosilicate tubes was
      found to accelerate their degradation rate with complete decomposition.
      Concomitantly, kinetic experimental results showed a critical difference of
      performance for the two coating methods used; in particular, the degradation
      rates of pollutants by the sol-gel-coated tubes were much faster than the
      degradation by the nanoparticle/PECVD-coated tubes. Using TiO2 supported on
      borosilicate tubes appears to be a promising alternative to conventional TiO2
      suspension and avoid post-separation stages. The results achieved in this study
      can be used to optimise large-scale applications, and expanding the study to
      cover a wide range of pollutants will lead to achieve more representative
      results.

PMID- 30117022
TI  - Fluorescein sodium-guided biopsy or resection in primary central nervous system
      lymphomas with contrast-enhancing lesion in MRI.
AB  - BACKGROUND: Surgical procedures are critical in making a conclusive
      histopathological diagnosis of primary central nervous system lymphoma (PCNSL),
      which typically presents contrast-enhancing lesions in magnetic resonance imaging
      (MRI). The fluorescein sodium-guided technique could enhance tumor visibility. We
      reported a series of patients with PCNSL underwent fluorescein sodium-guided
      surgical procedures. PATIENTS AND METHODS: 12 patients clinically considered
      brain tumors underwent fluorescein sodium-guided surgery in Sun Yat-sen
      University Cancer Center from March 2016 to July 2017. The age of 4 female and 8
      male patients ranges from 39 to 62 years. In 4 patients, corticosteroid had been
      prescribed before surgery due to intracranial hypertension. After injection of
      low dose of sodium fluorescein (3-5 mg/kg), the lesions with strong fluorescence
      staining were identified as the target area for biopsy or resection. RESULTS:
      Based on the targeted tissues with bright and homogenous fluorescence staining,
      all 12 patients were conclusively diagnosed as B cell non-Hodgkin's lymphoma
      (diffuse large cell). The specificity of the specimens sent for frozen section
      was 86.4% (19/22). No fluorescein sodium associated side effects were observed.
      CONCLUSION: Fluorescein sodium guided surgery is an effective and safe tool in
      biopsy or tumor resection in patients suspicious for PCNSL with preoperative MRI
      presented contrast-enhanced homogenous lesions. Such technique might still be
      considered in those patients who have been pretreated with corticosteroid.

PMID- 30117025
TI  - Intraspecific variation in sensitivity of winter wheat (Triticum aestivum L.) to
      ambient ozone in northern China as assessed by ethylenediurea (EDU).
AB  - Wheat is a major staple food and its sensitivity to the gas pollutant ozone (O3)
      depends on the cultivar. However, few chamber-less studies assessed current
      ambient O3 effects on a large number of wheat cultivars. In this study, we used
      ethylenediurea (EDU), an O3 protectant whose protection mechanisms are still
      unclear, to test photosynthetic pigments, gas exchange, antioxidants, and yield
      of 15 cultivars exposed to 17.4 ppm h AOT40 (accumulated O3 over an hourly
      concentration threshold of 40 ppb) over the growing season at Beijing suburb,
      China. EDU significantly increased light-saturated photosynthesis rate (Asat),
      photosynthetic pigments (i.e., chlorophyll and carotenoid), and total antioxidant
      capacity, while reduced malondialdehyde and reduced ascorbate contents. In
      comparison with EDU-treated plants (control), plants treated with water (no
      protection from ambient O3) significantly decreased yield, weight of 1000 grains,
      and harvest index by 20.3%, 15.1%, and 14.2%, respectively, across all cultivars.
      There was a significant interaction between EDU and cultivars in all tested
      variables with exception of Asat, chlorophyll, and carotenoid. The cultivar
      specific sensitivity to O3 was ranked from highly sensitive (> 25% change) to
      less sensitive (< 10% change) by comparing the difference of the average grain
      yield of plants applied with and without EDU. Neither stomatal conductance nor
      antioxidant capacity contributed to the different response of the cultivars to
      EDU, suggesting that another mechanism contributes to the large variation in
      response to O3 among cultivars. Generally, the results indicate that present O3
      concentration is threatening wheat production in Northern China, highlighting the
      urgent need for policy-making actions to protect this critical staple food.

PMID- 30117019
TI  - Perioperative Use of Intravenous Lidocaine.
AB  - Lidocaine is an amide local anaesthetic initially used intravenously as an
      antiarrhythmic agent. At some point it was proposed that intravenous lidocaine
      (IVL) had an analgesic effect that could be potentially beneficial in
      perioperative settings. Since these preliminary reports, a large body of evidence
      confirmed that IVL had anti-inflammatory and opiate-sparing effects, a
      combination of characteristics leading to an array of effects such as a decrease
      in postoperative pain and opiate consumption, and a reduction in the duration of
      digestive ileus. Additional studies demonstrated IVL to possess antithrombotic,
      antimicrobial and antitumoral effects. Beneficial effects of IVL have been
      characterized in abdominal surgery but remain controversial in other types of
      surgeries. Because the quality of evidence was limited, due to inconsistency,
      imprecision and study quality, recent conclusions from meta-analysis pooling
      together all types of surgery stated the uncertainty about IVL benefits.
      Additional indications such as the prevention of propofol-induced injection pain,
      prevention of hyperalgesia, protection against bronchial reactivity by
      bronchotracheal relaxation during surgery, and the increase in depth of general
      anaesthesia have since emerged. IVL is rapidly distributed in the body and
      metabolized by the liver. With the commonly recommended doses, lidocaine's
      therapeutic index remains very high and the plasma concentrations stay largely
      below the cardiotoxic and neurotoxic threshold levels, a notion that may be used
      by clinicians to draw conclusions on the benefit-risk profile of IVL in
      comparison to other analgesic strategies. The purpose of this review is to
      address the pharmacokinetic and pharmacodynamic properties of lidocaine in
      healthy and pathological conditions.

PMID- 30117026
TI  - Optimization process of organic matter removal from wastewater by using
      Eichhornia crassipes.
AB  - This study aimed to determine the optimal conditions for organic matter removal
      from wastewater by Eichhornia crassipes (E.C). As a matter of fact, a complete
      factorial design was used to determine the effect of residence time (X1), plant
      density (X2) and initial chemical oxygen demand (COD) concentration (X3) on the
      phytoremediation process. The process's performance was measured on COD (Y1),
      NH4+ (Y2) and PO43- (Y3), with the results indicating a reduction of 8.59-81.71%
      of COD (Y1); 22.53-95.81% of NH4+ (Y2) and 0.54-99.35% of PO43- (Y3). Then, the
      first-order models obtained for COD, NH4+ and PO43- removal were validated using
      different statistical approaches such as statistical and experimental validation.
      Moreover, multi-response optimization was carried out through different
      scenarios. On the whole, the results obtained indicated that two serial ponds are
      required for an optimum organic matter removal by Eichhornia crassipes. Indeed,
      for the first pond, a residence time of 15 days is needed with a plant density of
      60 ft/m2 and an initial concentration of about 944 mg/L. The second was the same
      residence time as the first with similar plant density of 60 ft/m2 and an initial
      load 192 mg/L (> 200 mg/L). Optimal organic matter removal from wastewater using
      Eichhornia crassipes requires two ponds arranged in chain.

PMID- 30117027
TI  - Water quality assessment of the most important dam (Latyan dam) in Tehran, Iran.
AB  - A pattern of water quality affected by the input regime and site specification is
      one of the most important issues in water supply resources and demand management.
      The present study aims to assess the water quality of Latyan dam, the important
      reservoir that supplies drinking water of Tehran, the capital city of Iran.
      Monthly water sampling was performed at four depths of the dam. The physical and
      chemical properties of water including temperature, pH, turbidity, total
      dissolved solids (TDS), electrical conductivity (EC), hardness, as well as Ca2+,
      Mg2+, Na+, K+, Cl-, SO42-, silica, ammonium, nitrate, nitrite, and total
      phosphorus (TP) concentration, were monitored from May 2014 to January 2017. The
      results of statistical analysis indicated that the quality of water in the dam
      was affected by the depth in view of five variables of EC, pH, turbidity, SO42-,
      and TP (p ? 0.05). Moreover, it was determined that ten out of 17 variables
      including EC, turbidity, TDS, Ca2+, K, Cl-, SO42-, silica, nitrate, and TP were
      statistically significant (p ? 0.05) based on seasonal variation analyses.
      Comparing the mean values, it could be concluded that EC, TDS, Ca2+, K+, Cl-, and
      SO42- were slightly higher during the winter probably owing to the diluting
      effects of seasonal precipitation. Nutrient-like distribution, nitrate, and TP,
      as well as silica, were much higher during the spring representing a high-diatoms
      activity and eutrophication. Turbidity was higher in the fall compared to the
      other seasons, which also demonstrated rainfall effects. Evaluation of the
      aggressiveness index (AI) suggests that water is moderately corrosive, and
      noncorrosive in the winter compared to other seasons. Moreover, according to the
      findings of this research and their comparison with the national and
      international water quality guidelines/standards, it could be said that the water
      quality of Latyan dam during the study period was acceptable and thus it was
      usable as a drinking water supply. However, due to the changes occurred in
      nitrate and phosphorus and extensive development of eutrophication problem,
      accurate and continuous evaluation of water quality in this reservoir is deemed
      necessary.

PMID- 30117028
TI  - Impact of trace element supplementation on mesophilic anaerobic digestion of food
      waste using Fe-rich inoculum.
AB  - Trace elements (TEs) play an indispensable role in enhancing the stability of
      anaerobic digestion (AD) of food waste (FW). Significant research on AD of FW
      with TE supplementation has been conducted with low Fe content inoculum. However,
      the use of Fe-rich inoculum is inevitable due to chemical phosphorous removal
      from wastewater in North America. We conducted comprehensive mesophilic batch
      tests to investigate the effect of TEs (Fe, Ni, Co, Se, and Mo) on FW digestion
      inoculated with Fe-rich sludge (>= 1000 mg Fe L-1). This paper presents the
      impact of supplementing various concentrations of TEs on specific methanogenic
      activity (SMA), maximum specific methane production rate (SMPRmax), and apparent
      hydrolysis rate constant (Kh). The addition of TEs adversely impacted
      methanogenic activity by 20 to 58% in the SMA tests. The effects of individual
      and mixed supplementation of TEs on the SMPRmax and Kh during FW digestion were
      negligible; exceptions include Fe, Mo, and Co. Final soluble TE concentrations
      were 10-29% of the initial soluble TEs. The high Fe concentration in the inoculum
      reduces the bioavailable fraction of added TEs via coprecipitation. Contrary with
      many literature reports indicating the need to supplement TE to improve FW
      digestion efficiency, with Fe-rich sludges, FW digestion does not require TE
      supplementation.

PMID- 30117029
TI  - Sun Exposure and Protection Index (SEPI) and Self-Estimated Sun Sensitivity.
AB  - The incidence of skin cancer is increasing worldwide, mostly because of
      increasing exposure to ultraviolet (UV) radiation from the sun. The Sun Exposure
      and Protection Index (SEPI) questionnaire, developed in Linkoping and validated
      in Sweden and Australia, is used to map sun habits, sun protection behaviour, and
      readiness to increase sun protection. We sought to examine differences in sun
      habits or sun protection behaviour and propensity to increase sun protection,
      based on SEPI as related to self-estimated skin UV sensitivity according to the
      Fitzpatrick classification. The study population comprised students at Linkoping
      University, who were asked to complete the SEPI questionnaire. We examined
      differences in sun habits and sun protection behaviour according to skin type and
      gender. Individuals with lower UV sensitivity had significantly riskier sun
      habits and sun protection behaviour and were significantly less likely to
      increase sun protection. Women spent significantly more time tanning than men,
      more time in the midday sun, used sunscreen more frequently, and were more likely
      to seek the shade for sun protection. Individuals with higher UV sensitivity were
      significantly more likely to increase sun protection; individuals with low UV
      sensitivity tended to have a riskier attitude to sunbathing. In conclusion, self
      estimated skin type and gender are important factors influencing sun exposure
      habits and sun protection behaviour.

PMID- 30117030
TI  - Taking a proactive role in patient management of important incidental imaging
      findings: How can we increase the 'value' of diagnostic radiology service and
      improve quality of patient care?

PMID- 30117031
TI  - Comparison of the association of predicted fat mass, body mass index, and other
      obesity indicators with type 2 diabetes risk: two large prospective studies in US
      men and women.
AB  - Obesity, defined by body mass index (BMI), is a well-established risk factor of
      type 2 diabetes, but BMI has been criticized for its inability to discriminate
      fat mass and lean body mass. We examined the association between predicted fat
      mass and type 2 diabetes risk in two large US prospective cohorts, and compared
      the magnitude of the association with BMI and other obesity indicators. Validated
      anthropometric prediction equations previously developed from the National Health
      and Nutrition Examination Survey were used to estimate predicted fat mass and
      percent fat for 97,111 participants from the Health Professionals Follow-up Study
      (1987-2012) and the Nurses' Health Study (1986-2012) who were followed up for
      type 2 diabetes. Multivariable-adjusted hazard ratios for type 2 diabetes across
      quintiles of predicted fat mass were 1.00, 1.96, 2.96, 3.90, and 8.38 for men and
      1.00, 2.20, 3.50, 5.73, and 12.1 for women; of BMI were 1.00, 1.69, 2.45, 3.54,
      and 6.94 for men and 1.00, 1.76, 2.86, 4.88, and 9.88 for women. Predicted FM
      showed the strongest association with type 2 diabetes in men followed by waist
      circumference (WC), waist-to-height ratio (WHtR), predicted percent fat, BMI,
      Waist-to-hip ratio (WHR), and a body shape index (ABSI). For women, the strongest
      association was shown for WHtR, followed by WC, predicted percent fat, predicted
      fat mass, BMI, ABSI, and WHR. Compared to BMI, predicted fat mass demonstrated
      consistently stronger association with type 2 diabetes risk. However, there was
      inconclusive evidence to suggest that predicted fat mass is substantially
      superior to other obesity indicators.

PMID- 30117033
TI  - Comparison of ability of pulse pressure variation to predict fluid responsiveness
      in prone and supine position: an observational study.
AB  - We aimed to compare the ability of pulse pressure variation (PPV) to predict
      fluid responsiveness in prone and supine positions and investigate effect of body
      mass index (BMI), intraabdominal pressure (IAP) and static respiratory compliance
      (CS) on PPV. A total of 88 patients undergoing neurosurgery were included. After
      standardized anesthesia induction, patients' PPV, stroke volume index (SVI), CS
      and IAP values were recorded in supine (T1) and prone (T2) positions and after
      fluid loading (T3). Also, PPV change percentage (PPVDelta%) between T2 and T1
      times was calculated. Patients whose SVI increased more than 15% after the fluid
      loading were defined as volume responders. In 10 patients, PPVDelta% was <= -
      20%. All of these patients had CST2 < 31 ml/cmH2O, seven had BMI > 30 kg/m2, and
      two had IAPT2 > 15 mmHg. In 16 patients, PPVDelta% was >= 20%. In these patients,
      10 had CST2 < 31 ml/cmH2O, 10 had BMI > 30 kg/m2, and 12 had IAPT2 > 15 mmHg.
      Thirty-nine patients were volume responder. When all patients were examined for
      predicting fluid responsiveness, area under curves (AUC) of PPVT2 (0.790, 95%CI
      0.690-0.870) was significantly lower than AUC of PPVT1 (0.937, 95%CI 0.878-0.997)
      with ROC analysis (p = 0.002). When patients whose CST2 was < 31 ml/cmH2O and
      whose BMI was > 30 kg/m2 were excluded from analysis separately, AUC of PPVT2
      became similar to PPVT1. PPV in the prone can predict fluid responsiveness as
      good as PPV in the supine, only if BMI is < 30 kg/m2 and CS value at prone is >
      31 ml/cmH2O.

PMID- 30117032
TI  - Laser Therapy for Genitourinary Syndrome of Menopause.
AB  - PURPOSE OF REVIEW: The purpose of this article is to review the available data
      regarding the application and therapeutic outcomes of laser therapy for the
      treatment of genitourinary syndrome of menopause (GSM). RECENT FINDINGS: There
      have been several studies regarding the use of laser therapy for the treatment of
      GSM. Most of these studies show a trend toward safe and effective treatment in
      the short term (less than or equal to 12 weeks). However, these studies are
      lacking in randomization, blinding, placebo, and comparison groups. Although
      laser therapy for the treatment of the symptoms of GSM appears promising, there
      is currently a lack of high-level and long-term evidence regarding its safety and
      efficacy. There is also a lack of professional guidelines in the USA regarding
      this modality of treatment, specifically for GSM. Opportunities exist for future
      research in this area, specifically to determine safety and long-term outcomes of
      therapy.

PMID- 30117034
TI  - Resonance assignments for the apo-form of the cellulose-active lytic
      polysaccharide monooxygenase TaLPMO9A.
AB  - The apo-form of the 24.4 kDa AA9 family lytic polysaccharide monooxygenase
      TaLPMO9A from Thermoascus aurantiacus has been isotopically labeled and
      recombinantly expressed in Pichia pastoris. In this paper, we report the 1H, 13C,
      and 15N chemical shift assignments, as well as an analysis of the secondary
      structure of the protein based on the secondary chemical shifts.

PMID- 30117035
TI  - A 22-bp deletion in OsPLS3 gene encoding a DUF266-containing protein is
      implicated in rice leaf senescence.
AB  - Key message The OsPLS3 locus was isolated by map-based cloning that encodes a
      DUF266-containing protein. OsPLS3 regulates the onset of leaf senescence in rice.
      Glycosyltransferases (GTs) are one of the most important enzyme groups required
      for the modification of plant secondary metabolites and play a crucial role in
      plant growth and development, however the biological functions of most GTs remain
      elusive. We reported here the identification and characterization of a novel
      Oryza sativa premature leaf senescence mutant (ospls3). Through map-based cloning
      strategy, we determined that 22-bp deletion in the OsPLS3 gene encoding a domain
      of unknown function 266 (DUF266)-containing protein, a member of GT14-like,
      underlies the premature leaf senescence phenotype in the ospls3 mutant. The
      OsPLS3 mRNA levels progressively declined with the age-dependent leaf senescence
      in wild-type rice, implying a negative role of OsPLS3 in regulating leaf
      senescence. Physiological analysis, and histochemical staining and transmission
      electron microscopy assays indicated that the ospls3 mutant accumulated higher
      levels of ethylene and reactive oxygen species than its wild type. Furthermore,
      the ospls3 mutant showed hypersensitivity to exogenous 1-aminocyclopropane-1
      carboxylic acid, H2O2 and high level of cytokinins. Our results indicated that
      the DUF266-containing gene OsPLS3 plays an important role in the onset of leaf
      senescence, in part through cytokinin and ethylene signaling in rice.

PMID- 30117036
TI  - Tenecteplase versus alteplase for management of acute ischemic stroke: a pairwise
      and network meta-analysis of randomized clinical trials.
AB  - Tenecteplase is a genetically mutated variant of alteplase with superior
      pharmacodynamic and pharmacokinetic properties. However, its efficacy and safety
      in acute ischemic strokes are limited. Hence, we conducted a study to evaluate
      the efficacy and safety of tenecteplase compared with alteplase in acute ischemic
      stroke. Electronic databases were searched for randomized clinical trials (RCTs)
      comparing tenecteplase with alteplase in acute ischemic stroke patients eligible
      for thrombolysis. We evaluated various efficacy and safety outcomes using random
      effects models for both pairwise and Bayesian network meta-analyses along with
      meta-regression analyses. We included 5 RCTs with a total of 1585 patients.
      Compared with alteplase, tenecteplase treatment was associated with significantly
      greater complete recanalization (odd ratio [OR] 2.01; 95% confidence interval
      [CI] 1.04-3.87; p = 0.04) and early neurological improvement (OR 1.43; 95% CI
      1.01-2.03; p = 0.05). There were no differences between the two thrombolytics in
      terms of excellent recovery (modified Rankin Scale [mRS] 0-1; OR 1.17; 95% CI
      0.95-1.44; p = 0.13), functional independence (mRS 0-2; OR 1.24; 95% CI 0.78
      1.98), poor recovery (mRS 4-6; OR 0.78; 95% CI 0.49-1.25; p = 0.31),
      complete/partial recanalization (OR 1.51; 95% CI 0.70-3.26; p = 0.30), any
      intracerebral hemorrhage (OR 0.81; 95% CI 0.56-1.17; p = 0.26), symptomatic
      intracerebral hemorrhage (OR 0.98; 95% CI 0.52-1.83; p = 0.94), or mortality (OR
      0.83; 95% CI 0.54-1.26; p = 0.38). In network meta-analysis, there were better
      efficacy and imaging-based outcomes with tenecteplase 0.25 mg/kg without
      increased risk of safety outcomes. Our results demonstrate that in acute ischemic
      stroke, thrombolysis with tenecteplase is at least as effective and safe as
      alteplase.

PMID- 30117037
TI  - Unexpected fluctuations of trace element levels in cell culture medium in vitro:
      caveat emptor.
AB  - Copper is an essential trace element micronutrient in human and animal nutrition.
      Trace amounts present even in ultrapure water, serum and other cell culture
      medium components are sufficient to support the health requirements of most cell
      types in culture. Analysis of a variety of different types of basal media from a
      number of different suppliers revealed large fluctuations in the levels of
      copper, and also of other micronutrients including zinc, iron, selenium and
      cobalt. Investigations on proliferating Caco-2 cells revealed reductions in
      growth with increasing copper concentrations within the range seen in the
      commercial media and changes in expression of apoptosis- and autophagy-related
      proteins were noted. Even at concentrations of 1 MUM CuSO4 where there was no
      significant change in cell growth, there was a significant decrease in procaspase
      3 expression. These results stress the importance of batch testing of basal media
      when undertaking trace metal research since the baseline levels may vary. Batch
      variation of serum is well established but our results suggest that batch
      variation of the media may also be important.

PMID- 30117038
TI  - Conformationally locked lanthanide chelating tags for convenient pseudocontact
      shift protein nuclear magnetic resonance spectroscopy.
AB  - Pseudocontact shifts (PCS) generated by lanthanide chelating tags yield valuable
      restraints for investigating protein structures, dynamics and interactions in
      solution. In this work, dysprosium-, thulium- and terbium-complexes of eight-fold
      methylated 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid tags [DOTA-M8
      (4R4S)-SSPy] are presented that induce large pseudocontact shifts up to 5.5 ppm
      and adopt exclusively the square antiprismatic conformation. This is in contrast
      to our earlier findings on complexes of the stereoisomeric DOTA-M8-(8S)-SSPy,
      where significant amounts of the twisted square antiprismatic conformer for the
      Dy tag were observed. The Dy-, Tm-, Tb- and Lu-complexes of DOTA-M8-(4R4S)-SSPy
      were conjugated to ubiquitin S57C and selectively 15N leucine labeled human
      carbonic anhydrase II S50C, resulting in only one set of signals. Furthermore, we
      investigated the conformation of the thulium- and dysprosium-complexes in vacuo
      and with implicit water solvent using density functional theory calculations. The
      calculated energy differences between the two different conformations (7.0-50.5
      kJ/mol) and experimental evidence from the corresponding ytterbium- and yttrium
      complexes clearly suggest a SAP [Lambda(deltadeltadeltadelta)] geometry for the
      complexes presented in this study. The lanthanide chelating tag studied in this
      work offer insights into the solution structure of proteins by inducing strong
      pseudocontact shifts, show different tensor properties compared to its
      predecessor, enables a convenient assignment procedure, is accessed by a more
      economic synthesis than its predecessor and constitutes a highly promising
      starting point for further developments of lanthanide chelating tags.

PMID- 30117039
TI  - Association of baseline patient characteristics with adjuvant chemotherapy
      toxicities in stage III colorectal cancer patients.
AB  - Toxicities can affect cancer patients' quality of life resulting in poor
      adherence to adjuvant chemotherapy (AC). While previous studies have explored the
      prevalence of toxicities following AC, few have examined the associations of
      baseline characteristics, such as age, sex, and performance status, with toxicity
      outcomes. In this study, we reviewed a cohort of 371 colorectal cancer patients
      treated with adjuvant monotherapy (capecitabine ) or combination therapy (FOLFOX
      or CAPOX) within 12 weeks of curative resection, and determined the associations
      between baseline characteristics and toxicity outcomes. Median age was 65 years,
      52% were men, and 41% received monotherapy. A number of toxicities appeared to
      decrease with successive AC cycles. For monotherapy, univariate analyses found
      that age, sex, performance status, and pre-treatment anemia were associated with
      hematological toxicities whereas tumor location was associated with
      gastrointestinal (GI) toxicities (all P < 0.05). On multivariate analyses,
      hematological toxicities were predicted by advanced age (>= 70) (OR 3.30; 95% CI
      1.17-9.37; P = 0.025) and pre-treatment anemia (OR 23.18; 95% CI 6.36-84.48; P <
      0.001), while GI toxicities were less likely to occur among tumors at or distal
      to the splenic flexure (OR 0.38; 95% CI 0.15-0.99; P = 0.047). For combination
      therapy, sex and pre-treatment anemia were associated with hematological
      toxicities (all P < 0.05), but only female sex was predictive on multivariate
      analyses (OR 5.13; 95% CI 2.08-12.68; P < 0.001). In conclusion, few baseline
      characteristics were associated with treatment toxicities. These findings may
      better inform discussions with patients and caregivers during AC decision-making
      and underscore to clinicians the need for close monitoring of patients during
      treatment.

PMID- 30117041
TI  - Particle Size Distribution Equivalency as Novel Predictors for Bioequivalence.
AB  - The use of particle size distribution (PSD) similarity metrics and the
      development and incorporation of drug release predictions based on PSD properties
      into PBPK models for various drug administration routes may provide a holistic
      approach for evaluating the effect of PSD differences on in vitro drug release
      and bioavailability of disperse systems. The objectives of this study were to
      provide a rational approach for evaluating the utility of in vitro PSD
      comparators for predicting bioequivalence for subcutaneously administered test
      and reference drug emulsions. Two types of in vitro comparators for test and
      reference emulsion products were evaluated: PSD characterization comparators
      (overlap metrics, median, and span ratios) and release profile comparators (f2
      and various fractional time ratios). A subcutaneous-input PBPK disposition model
      was developed to simulate blood concentration-time profiles of reference and test
      emulsion products and pharmacokinetic responses (e.g., AUC, Cmax, and Tmax) were
      used to determine bioequivalence. A pool of 10,440 pairs of test and reference
      products was simulated using Monte Carlo experiments. The PSD and release profile
      comparators were correlated to pass/fail bioequivalence metrics using logistical
      regression. Based on the use of single in vitro comparators, the f2 method was
      the best predictor of bioequivalence prediction. The use of combinations of f2
      and PSD overlap comparators (e.g., OVL or PROB) improved bioequivalence
      prediction to about 90%. Simulation procedures used in this study demonstrated a
      process for developing reliable in vitro BE predictors.

PMID- 30117040
TI  - Cervico-vaginal mucus (CVM) - an accessible source of immunologically informative
      biomolecules.
AB  - Cervico-vaginal mucus (CVM), the product of epithelial cells lining the uterus,
      cervix and vagina, is secreted to facilitate uterine lubrication and microbial
      clearance. Predominantly composed of water and mucins, CVM also contains high
      levels of immuno-active proteins such as immunoglobulin A (IgA), lactoferrin and
      lysozyme which protect against infection by blocking adhesion and mediating
      microbial killing. The repertoire of cytokines, chemokines and antimicrobial
      peptides is predominantly generated by the secretions of endometrial epithelial
      cells into the uterine lumen and concentrated in the CVM. The quantity and
      relative proportions of these inflammatory biomarkers are affected by diverse
      factors including the estrus cycle and health status of the animal and therefore
      potentially provide important diagnostic and prognostic indicators. We propose
      that measuring molecular signatures in bovine CVM could be a useful approach to
      identifying and monitoring genital tract pathologies in beef and dairy cows.

PMID- 30117044
TI  - A stable feature extraction method in classification epileptic EEG signals.
AB  - Epilepsy is one of the most common neurological disorders. Electroencephalogram
      (EEG) signals are generally employed in diagnosing epilepsy. Therefore,
      extracting relevant features from EEG signals is one of the major tasks in an
      accurate diagnosis. In this study, the local ternary patterns, which is an image
      processing method, was improved in order to extract robust features from
      epileptic EEG signals. The EEG signals that were recorded by the Department of
      Etymology in the Bonn University were employed in the evaluation and validation
      of the proposed approach. Low and up features, which were extracted by the
      proposed one-dimensional ternary patterns, were classified by some machine
      learning methods such that support vector machine, functional trees, random
      forest (RF), Bayes networks (BayesNet), and artificial neural network, while the
      highest accuracies were obtained by RF. Achieved accuracies were found successful
      according to the current literature.

PMID- 30117042
TI  - Apoptosis Induction and Antimigratory Activity of Andrographolide Analog (3A.1)
      Incorporated Self-Assembled Nanoparticles in Cancer Cells.
AB  - Andrographolide analog, namely 19-tert-butyldiphenylsilyl-8,17-epoxy
      andrographolide (or 3A.1) has been reported to be a potential anticancer agent
      for several types of cancer. Due to its poor aqueous solubility, 3A.1 was
      incorporated within self-assembly polymeric nanoparticles made of naphthyl
      grafted succinyl chitosan (NSC), octyl-grafted succinyl chitosan (OSC), and
      benzyl-grafted succinyl chitosan (BSC). These 3A.1-loaded nanoparticles were
      nanosized (< 200 nm) and spherical in shape with a negative surface charge. 3A.1
      loaded nanoparticles were produced using a dropping method, which 40% initial
      drug adding exhibited the highest entrapment efficiency. The release of 3A.1 from
      the 3A.1-loaded nanoparticles displayed a delayed release pattern. Under acidic
      conditions (pH 1.2), there was no free drug release. After the pH was adjusted to
      6.8, a high cumulative 3A.1 release was obtained which was dependent on the
      hydrophobic moieties. These 3A.1-loaded pH-sensitive nanoparticles proved to be
      beneficial for specifically delivering anticancer drugs to the targeted colon
      cancer sites. In vitro anticancer activity against HT-29 found that the 3A.1
      loaded nanoparticles had significantly lower IC50 than that of the free drug and
      promoted apoptosis. Additionally, in vitro wound-healing migration on HN-22
      revealed that free 3A.1 and the 3A.1-loaded nanoparticles inhibited cell motility
      compared with untreated cells. These pH-sensitive amphiphilic chitosan
      nanoparticles may be promising nanocarriers for oral anticancer drug delivery to
      colorectal cancer cells. Graphical abstract ?.

PMID- 30117043
TI  - Development of robust, fast and efficient QRS complex detector: a methodological
      review.
AB  - The basis and reliability for timely diagnosis of cardiovascular diseases depend
      on the robust and accurate detection of QRS complexes along with the fiducial
      points in the electrocardiogram (ECG) signal. Despite, the several QRS detection
      algorithms reported in the literature, the development of an efficient QRS
      detector remains a challenge in the clinical environment. Therefore, this article
      summarizes the performance analysis of various QRS detection techniques depending
      upon three assessment factors which include robustness to noise, computational
      load, and sensitivity validated on the benchmark MIT-BIH arrhythmia database.
      Moreover, the limitations of these algorithms are discussed and compared with the
      standard signal processing algorithms, followed by the future suggestions to
      develop a reliable and efficient QRS methodology. Further, the suggested method
      can be implemented on suitable hardware platforms to develop smart health
      monitoring systems for continuous and long-term ECG assessment for real-time
      applications.

PMID- 30117045
TI  - Iron chelator deferiprone rescues memory deficits, hippocampal BDNF levels and
      antioxidant defenses in an experimental model of memory impairment.
AB  - Brain-derived neurotrophic factor (BDNF) plays a key role in neural development
      and physiology, as well as in pathological states. Post-mortem studies
      demonstrate that BDNF is reduced in the brains of patients affected by
      neurodegenerative diseases. Iron accumulation has also been associated to the
      pathogenesis of neurodegenerative diseases. In rats, iron overload induces
      persistent memory deficits, increases oxidative stress and apoptotic markers, and
      decreases the expression of the synaptic marker, synaptophysin. Deferiprone (DFP)
      is an oral iron chelator used for the treatment of systemic iron overload
      disorders, and has recently been tested for Parkinson's disease. Here, we
      investigated the effects of iron overload on BDNF levels and on mRNA expression
      of genes encoding TrkB, p75NTR, catalase (CAT) and NQO1. We also aimed at
      investigating the effects of DFP on iron-induced impairments. Rats received iron
      or vehicle at postnatal days 12-14 and when adults, received chronic DFP or water
      (vehicle). Recognition memory was tested 19 days after the beginning of chelation
      therapy. BDNF measurements and expression analyses in the hippocampus were
      performed 24 h after the last day of DFP treatment. DFP restored memory and
      increased hippocampal BDNF levels, ameliorating iron-induced effects. Iron
      overload in the neonatal period reduced, while treatment with DFP was able to
      rescue, the expression of antioxidant enzymes CAT and NQO1.

PMID- 30117046
TI  - Modulatory Effect of the Supplemented Copper Ion on In Vitro Activity of Bovine
      Lactoferrin to Murine Splenocytes and RAW264.7 Macrophages.
AB  - Bovine lactoferrin (LF) was supplemented with Cu2+ at three contents of 0.16,
      0.32, and 0.64 mg/g LF, respectively. After then, LF and Cu-supplemented LF
      products were assessed for immuno-modulation in murine splenocytes and RAW264.7
      macrophages, using dose levels of 10-40 MUg/mL and four evaluation reflectors
      including stimulation index of splenocytes, T lymphocyte subpopulations,
      macrophage phagocytosis, and cytokine secretion. The results indicated that LF
      and Cu-supplemented LF products had suppression on splenocytes as well as
      concanavalin A (ConA)- or lipopolysaccharide-stimulated splenocytes; however,
      using lower Cu-supplementation content (i.e., 0.16 mg/g LF) and lower dose level
      (10 MUg/mL) alleviated this suppression significantly (P < 0.05). Compared to LF,
      Cu-supplemented LF product of lower Cu-supplementation content at lower dose
      level yielded slightly enhanced macrophage stimulation, increased CD4+/CD8+ ratio
      of T lymphocyte subpopulations in ConA-stimulated splenocytes, and significant
      secretion enhancement for interleukin-2 (IL-2), IL-4, interferon-gamma (in
      splenocytes), IL-1beta, and tumor necrosis factor-alpha (in macrophages) (P <
      0.05). Furthermore, Cu-supplemented LF product of higher Cu-supplementation
      content (i.e., 0.64 mg/g LF) at higher dose level mostly showed opposite effects
      in the cells, in comparison with its counterpart at lower dose level. It is
      concluded that Cu-supplementation of LF can alleviate or increase LF's effects on
      the two immune cells, and moreover, Cu content of supplemented LF is a key factor
      that modulates these effects.

PMID- 30117047
TI  - Cloning, Expression, and Bioinformatics Analysis of Heavy Metal Resistance Gene
      afe_1862 from Acidithiobacillus ferrooxidans L1 in Escherichia coli.
AB  - Molecular studies of copper and cadmium resistances in acidophilic bacteria are
      significant in biomining. In this study, afe_1862, which encodes a heavy metal
      binding protein in Acidithiobacillus ferrooxidans L1, was amplified using PCR,
      cloned into the pET32a plasmid, and sequenced. Following SDS-PAGE analysis,
      optimization of the expression conditions and heterologous overexpression of
      afe_1862 in Escherichia coli BL21 in the presence of Cu2+ and Cd2+ were studied
      as well. The results indicated that AFE_1862 has higher resistance to Cu2+ than
      Cd2+. Bioinformatics analysis illustrated that AFE_1862 has a conserved HMA
      domain containing heavy metal-binding sites, which may play a role in
      transporting or detoxifying heavy metals.

PMID- 30117048
TI  - A Novel Wavelet Transform-Homogeneity Model for Sudden Cardiac Death Prediction
      Using ECG Signals.
AB  - Sudden cardiac death (SCD) is one of the main causes of death among people. A new
      methodology is presented for predicting the SCD based on ECG signals employing
      the wavelet packet transform (WPT), a signal processing technique, homogeneity
      index (HI), a nonlinear measurement for time series signals, and the Enhanced
      Probabilistic Neural Network classification algorithm. The effectiveness and
      usefulness of the proposed method is evaluated using a database of measured ECG
      data acquired from 20 SCD and 18 normal patients. The proposed methodology
      presents the following significant advantages: (1) compared with previous works,
      the proposed methodology achieves a higher accuracy using a single nonlinear
      feature, HI, thus requiring low computational resource for predicting an SCD
      onset in real-time, unlike other methodologies proposed in the literature where a
      large number of nonlinear features are used to predict an SCD event; (2) it is
      capable of predicting the risk of developing an SCD event up to 20 min prior to
      the onset with a high accuracy of 95.8%, superseding the prior 12 min prediction
      time reported recently, and (3) it uses the ECG signal directly without the need
      for transforming the signal to a heart rate variability signal, thus saving time
      in the processing.

PMID- 30117049
TI  - Management of Bariatric Complications Using Endoscopic Stents: a Multi-Center
      Study.
AB  - BACKGROUND: Complications after bariatric procedures including leaks and
      strictures can be difficult to treat. Endoscopic treatment may be preferable due
      to its less invasiveness. The aim of this study is to describe usage of stents in
      treating complications after bariatric procedures, along with its indications,
      methods, and outcome. MATERIAL AND METHODS: A total of 87 patients underwent
      endoscopic stenting after a bariatric procedure from January 1, 2013, and
      December 31, 2016, in four bariatric centers. Previous bariatric procedures
      included Roux-en-Y gastric bypass (RYGB) (n = 33), sleeve gastrectomy (n = 50),
      duodenal switch (DS, n = 2), and vertical banded gastroplasty (VBG, n = 2).
      RESULTS: Mean age at intervention was 42.6 +/- 10.0 years old, and mean body mass
      index was 41.6 +/- 4.0 kg/m2 at the time of bariatric procedure. Reasons for
      stenting included sleeve leakage (n = 48), gatrojejunostomy (GJ) leakage (n =
      21), stricture (n = 8), staple-line disruption (n = 7), and obstruction at the
      site of ring (n = 2). Migration occurred in 19.5% (n = 17) of patients undergoing
      stent placement and required repositioning or replacement of stents. Stenosis
      occurred in 13.8% of patients, which required endoscopic dilatation after stent
      removal. CONCLUSION: Stents may be useful and effective in managing complications
      after different bariatric procedures, including RYGB and LSG.

PMID- 30117050
TI  - Ceftibuten plus amoxicillin-clavulanic acid for oral treatment of urinary tract
      infections with ESBL producing E. coli and K. pneumoniae: a retrospective
      observational case-series.
AB  - This study aimed to evaluate the clinical and bacteriological effect of oral
      treatment with ceftibuten plus amoxicillin-clavulanic acid in patients with a
      urinary tract infection (UTI) caused by an extended-spectrum beta-lactamase
      (ESBL)-producing micro-organism. In this retrospective observational case-series,
      oral treatment with ceftibuten 400 mg QD plus amoxicillin-clavulanic acid 625 mg
      TID for 14 days was evaluated in ten patients with pyelonephritis caused by an
      ESBL-positive micro-organism resistant to ciprofloxacin and co-trimoxazole.
      Presence of ESBL genes was confirmed using PCR and micro-array. EUCAST
      breakpoints were used for susceptibility testing. Ten patients (five women) were
      evaluated in 2016 and 2017. Six patients were from outpatient hospital care, and
      four from primary care. Urinary cultures yielded seven E. coli and three K.
      pneumoniae ESBL-positive isolates. Using Vitek-2, all isolates were resistant to
      cefotaxime, and resistant (n = 7) or intermediately susceptible (n = 3) to
      ceftazidime. With disc diffusion, all isolates were susceptible to ceftibuten
      (zones 25-32 mm), while with MIC test strips eight of ten isolates were resistant
      to ceftibuten (MICs 0.5-4 mg/L). An amoxicillin-clavulanic acid disc next to the
      ceftibuten disc extended the ceftibuten zone by 2-8 mm. All patients experienced
      clinical cure. Bacteriological cure (absence of pretreatment micro-organism in
      the first follow-up culture obtained within 3 months after treatment) was
      observed in all eight patients with follow-up cultures. This case-series shows
      that the synergistic combination of ceftibuten plus amoxicillin-clavulanic acid
      may be an option for oral treatment of UTIs caused by ESBL producing E. coli or
      K. pneumoniae.

PMID- 30117051
TI  - The Prevalence of Dose Errors Among Paediatric Patients in Hospital Wards with
      and without Health Information Technology: A Systematic Review and Meta-Analysis.
AB  - INTRODUCTION: The risk of dose errors is high in paediatric inpatient settings.
      Computerized provider order entry (CPOE) systems with clinical decision support
      (CDS) may assist in reducing the risk of dosing errors. Although a frequent type
      of medication error, the prevalence of dose errors is not well described. Dosing
      error rates in hospitals with or without CPOE have not been compared. OBJECTIVE:
      Our aim was to conduct a systematic review assessing the prevalence and impact of
      dose errors in paediatric wards with and without CPOE and/or CDS. METHODS: We
      systematically searched five databases to identify studies published between
      January 2000 and December 2017 that assessed dose error rates by medication chart
      audit or direct observation. RESULTS: We identified 39 studies, nine of which
      involved paediatric wards using CPOE with or without CDS. Studies of paediatric
      wards using paper medication charts reported approximately 8-25% of patients
      experiencing a dose error, and approximately 2-6% of medication orders and
      approximately 3-8% of dose administrations contained a dose error, with estimates
      varying by ward type. The nine studies of paediatric wards using CPOE reported
      approximately 22% of patients experiencing a dose error, and approximately 1-6%
      of medication orders and approximately 3-8% of dose administrations contained a
      dose error. Few studies provided data for individual wards. The severity and
      prevalence of harm associated with dose errors was rarely assessed and showed
      inconsistent results. CONCLUSIONS: Dose errors occur in approximately 1 in 20
      medication orders. Hospitals using CPOE with or without CDS had a lower rate of
      dose errors compared with those using paper charts. However, few pre/post studies
      have been conducted and none reported a significant reduction in dose error rates
      associated with the introduction of CPOE. Future research employing controlled
      designs is needed to determine the true impact of CPOE on dosing errors among
      children, and any associated patient harm.

PMID- 30117052
TI  - Efficacy and safety of long pulse Nd:YAG laser versus fractional erbium:YAG laser
      in the treatment of facial skin wrinkles.
AB  - Fractional lasers such erbium:YAG (Er:YAG) are among popular options for facial
      rejuvenation. Lasers with infrared wavelength ranges such as long pulse Nd:YAG
      have been used in nonablative rejuvenation of skin with variable outcomes. In
      this study, we plan to compare safety and efficacy of fractional Er:YAG and long
      pulse Nd:YAG for facial rejuvenation applying objective and subjective
      measurements. Twenty-five patients with Glogau photo aging scale of II to IV were
      recruited in this randomized face-split double-blind controlled trial.
      Individuals received three monthly treatments on two sides of the face; one side
      was treated by fractional Er:YAG laser and the other side by long pulse Nd:YAG
      laser. Outcomes were evaluated by two blinded dermatologists, patient
      satisfaction reports and objective measurements of cutaneous resonance running
      time (CRRT). Both modalities significantly improved periorbital wrinkling,
      nasolabial folds, dyschromia and skin laxity, and sagging of jowls (p value <
      0.05), with no noticeable difference between two lasers. Mean CRRT values
      decreased significantly after treatment with both lasers. The downtime was
      significantly lower for the Nd:YAG-treated side. Fractional Er:YAG laser and long
      pulse Nd:YAG has comparable effects in facial rejuvenation but little to no
      downtime of the latter makes it popular for many patients. ClinicalTrials.gov
      Identifier: IRCT2015120320468N3.

PMID- 30117053
TI  - Intra- and Inter-Muscular Variations in Hamstring Architecture and Mechanics and
      Their Implications for Injury: A Narrative Review.
AB  - Understanding the architecture, anatomy, and biomechanics of the hamstrings may
      assist in explaining the mechanisms that affect and improve their function. The
      aim of this review is to specifically examine intra- and inter-muscular
      variations in architecture and mechanical properties of the hamstrings. Of the
      hamstrings, the long head of the biceps femoris shows the shortest and more
      pennated fibers. The semimembranosus has a similar muscle architecture with a
      long head of the biceps femoris but it has a different proximal attachment as
      well as a different moment arm compared with the long head of the biceps femoris.
      For the same joint motion, the semitendinosus displays less relative strain than
      the other hamstrings probably owing to a greater length, longer fascicles and,
      possibly, a longer tendon. Intra-muscular variations in architecture are
      documented but their implications are currently unclear. Proximally, the long
      head of the biceps femoris has shorter and more pennated fibers coupled with a
      narrower aponeurosis than distally, while the semitendinosus is the only muscle
      that entails a tendinous inscription. In conclusion, some of the identified intra
      and inter-muscular variations in architecture may help explain why some muscles
      sustain injuries more than others. In the same line, exercises designed for the
      hamstrings may not provide the same stimulus for all components of this muscle
      group. Future research could examine whether intervention strategies that target
      specific muscles or specific areas of the hamstrings may offer additional
      benefits for injury prevention or rehabilitation of their function.

PMID- 30117056
TI  - Tracking Declines in Mercury Exposure in the New York City Adult Population, 2004
      2014.
AB  - Mercury is a toxic metal that can be measured in human blood and urine.
      Population-based biomonitoring from 2004 guided New York City (NYC) Department of
      Health and Mental Hygiene (DOHMH) efforts to reduce exposures by educating the
      public about risks and benefits of fish consumption-a predominant source of
      exposure in the general population-and removing mercury-containing skin
      lightening creams and other consumer products from the marketplace. We describe
      changes in exposures over the past decade in relation to these local public
      health actions and in the context of national changes by comparing mercury
      concentrations measured in blood (1201 specimens) and urine (1408 specimens) from
      the NYC Health and Nutrition Examination Survey (NYC HANES) 2013-2014 with
      measurements from NYC HANES 2004 and National Health and Nutrition Examination
      Surveys (NHANES) 2003-2004 and 2013-2014. We found that NYC adult blood and urine
      geometric mean mercury concentrations decreased 46% and 45%, respectively. Adult
      New Yorkers with blood mercury concentration >= 5 MUg/L (the New York State
      reportable level) declined from 24.8% (95% CL = 22.2%, 27.7%) to 12.0% (95% CL =
      10.1%, 14.3%). The decline in blood mercury in NYC was greater than the national
      decline, while the decline in urine mercury was similar. As in 2004, Asian New
      Yorkers had higher blood mercury concentrations than other racial/ethnic groups.
      Foreign-born adults of East or Southeast Asian origin had the highest prevalence
      of reportable levels (29.7%; 95% CL = 21.0%, 40.1%) across sociodemographic
      groups, and Asians generally were the most frequent fish consumers, eating on
      average 11 fish meals in the past month compared with 7 among other groups (p <
      0.001). Fish consumption patterns were similar over time, and fish continues to
      be consumed more frequently in NYC than nationwide (24.7% of NYC adults ate fish
      ten or more times in the past 30 days vs. 14.7% nationally, p < 0.001). The
      findings are consistent with the hypothesis that blood mercury levels have
      declined in part because of local and national efforts to promote consumption of
      lower mercury fish. Local NYC efforts may have accelerated the reduction in
      exposure. Having "silver-colored fillings" on five or more teeth was associated
      with the highest 95th percentile for urine mercury (4.06 MUg/L; 95% CL = 3.1,
      5.9). An estimated 5.5% of the adult population (95% CL = 4.3%, 7.0%) reported
      using a skin-lightening cream in the past 30 days, but there was little evidence
      that use was associated with elevated urine mercury in 2013-14.

PMID- 30117054
TI  - The Effects of Balance Training on Balance Performance and Functional Outcome
      Measures Following Total Knee Arthroplasty: A Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Several studies have examined the effects of balance training in
      elderly individuals following total knee arthroplasty (TKA), although findings
      appear to be equivocal. OBJECTIVES: This systematic review and meta-analysis
      examined the effects of balance training on walking capacity, balance-specific
      performance and other functional outcome measures in elderly individuals
      following TKA. METHODS: Data sources: Pubmed, PEDro, Cinahl, SportDiscus, Scopus.
      Eligibility criteria: Data were aggregated following the population-intervention
      comparison-outcome (PICO) principles. Eligibility criteria included: (1)
      randomised controlled trials; (2) studies with comparative groups; (3) training
      interventions were incorporated post-TKA; and (4) outcome measures included
      walking capacity, balance-specific performance measures, subjective measures of
      physical function and pain and knee range-of-motion. PARTICIPANTS: Elderly
      individuals (65 + years) who underwent total knee arthroplasty. INTERVENTIONS:
      Balance interventions that consisted of balance exercises, which were compared to
      control interventions that did not involve balance exercises, or to a lesser
      extent. Participants also undertook usual physiotherapy care in conjunction with
      either the balance and/or control intervention. The intervention duration ranged
      from 4 to 32 weeks with outcome measures reported immediately following the
      intervention. Of these, four studies also reported follow-up measures ranging
      from 6 to 12 months post-interventions. Study appraisal: PEDro scale. SYNTHESIS
      METHODS: Quantitative analysis was conducted by generating forest plots to report
      on standardised mean differences (SMD; i.e. effect size), test statistics for
      statistical significance (i.e. Z values) and inter-trial heterogeneity by
      inspecting I2. A meta-regression was also conducted to determine whether training
      duration predicted the magnitude of SMD. RESULTS: Balance training exhibited
      significantly greater improvement in walking capacity (SMD = 0.57; Z = 6.30; P <
      0.001; I2 = 35%), balance-specific performance measures (SMD = 1.19; Z = 7.33; P
      < 0.001; I2 = 0%) and subjective measures of physical function (SMD = 0.46; Z =
      4.19; P < 0.001; I2 = 0%) compared to conventional training immediately post
      intervention. However, there were no differences in subjective measures of pain
      (SMD = 0.77; Z = 1.63; P > 0.05; I2 = 95%) and knee range-of-motion (SMD = 0.05;
      Z = 0.39; P > 0.05; I2 = 1%) between interventions. At the 6- to 12-month follow
      up period, improvement in combined measures of walking capacity and balance
      performance (SMD = 041; Z = 3.55; P < 0.001; I2 = 0%) were significantly greater
      for balance training compared to conventional training, although no differences
      were observed for subjective measures of physical function and pain (SMD = 0.26;
      Z = 2.09; P > 0.05; I2 = 0%). Finally, the training duration significantly
      predicted subjective measures of pain and physical function (r2 = 0.85;
      standardised beta = 0.92; P < 0.001), although this was not observed for walking
      capacity and balance-specific performance measures (r2 = 0.02; standardised beta
      = 0.13; P = 0.48). LIMITATIONS: A number of outcome measures indicated high inter
      trial heterogeneity and only articles published in English were included.
      CONCLUSION: Balance training improved walking capacity, balance-specific
      performance and functional outcome measures for elderly individuals following
      TKA. These findings may improve clinical decision-making for appropriate post-TKA
      exercise prescription to minimise falls risks and optimise physical function.

PMID- 30117055
TI  - Safety and Efficacy of DPP4 Inhibitor and Basal Insulin in Type 2 Diabetes: An
      Updated Review and Challenging Clinical Scenarios.
AB  - The safety and efficacy of dipeptidyl peptidase-4 (DPP4) inhibitors as
      monotherapy or in combination with other oral antidiabetic agents or basal
      insulin are well established. DPP4 inhibitors stimulate glucose-dependent insulin
      secretion and inhibit glucagon production. As monotherapy, they reduce the
      hemoglobin A1c level by about 0.6-0.8%. The addition of a DPP4 inhibitor to basal
      insulin is an attractive option, because they lower both postprandial and fasting
      plasma glucose concentrations without increasing the risk of hypoglycemia or
      weight gain. The present review summarizes the extensive evidence on the
      combination therapy of DPP4 inhibitors and insulin-based regimens in patients
      with type 2 diabetes. We focus our discussion on challenging clinical scenarios
      including patients with chronic renal impairment, elderly persons and
      hospitalized patients. The evidence indicates that these drugs are highly
      effective and safe in the elderly and in the presence of mild, moderate and
      severe renal failure improving glycemic control with low risk of hypoglycemia. In
      addition, several randomized-controlled trials have shown that the use of DPP4
      inhibitors in combination with basal insulin represents an alternative to the
      basal-bolus insulin regimen in hospitalized patients with type 2 diabetes.

PMID- 30117057
TI  - Correction to: Association between Firearm Laws and Homicide in Urban Counties.
AB  - The authors would like to publish this erratum to correct estimates generated
      from regression analyses due to errors discovered in the coding of some state
      laws.

PMID- 30117059
TI  - Pompe Disease: From Basic Science to Therapy.
AB  - Pompe disease is a rare and deadly muscle disorder. As a clinical entity, the
      disease has been known for over 75 years. While an optimist might be excited
      about the advances made during this time, a pessimist would note that we have yet
      to find a cure. However, both sides would agree that many findings in basic
      science-such as the Nobel prize-winning discoveries of glycogen metabolism, the
      lysosome, and autophagy-have become the foundation of our understanding of Pompe
      disease. The disease is a glycogen storage disorder, a lysosomal disorder, and an
      autophagic myopathy. In this review, we will discuss how these past discoveries
      have guided Pompe research and impacted recent therapeutic developments.

PMID- 30117058
TI  - Prediction and Prevention of Type 2 Diabetes in Women with a History of GDM.
AB  - PURPOSE OF THE REVIEW: Women with a history of gestational diabetes mellitus
      (GDM) have an alarmingly high risk of developing type 2 diabetes (T2D); yet,
      mechanisms underlying this progression are largely unknown. RECENT FINDINGS:
      Clinical characteristics of a GDM pregnancy and postpartum metabolomics may
      contribute to risk prediction of T2D to identify those women at highest risk of
      progression and need for intervention. Evidence for effective postpartum
      lifestyle interventions from observational studies include adherence to a healthy
      dietary pattern, increasing physical activity, and maintaining a healthy body
      weight. Larger clinical trials with greater participant engagement are warranted
      to confirm the effectiveness of lifestyle interventions in women with recent GDM.
      Research is needed to refine prediction models of T2D after GDM, and to determine
      the most effective strategies to delay or prevent T2D onset. Incorporating novel
      biomarkers in the postpartum period, such as metabolomics, could offer a powerful
      approach.

PMID- 30117060
TI  - Correction to: Patterns of Bicalutamide Use in Prostate Cancer Treatment: A U.S.
      Real-World Analysis Using the SEER-Medicare Database.
AB  - The original article can be found online.

PMID- 30117061
TI  - Creating Play Atmosphere and Time for Children in Chinese Kindergarten:
      Difficulties and Reflection.
AB  - Schools' busy situation is far away from its Greek root "Schole" that means
      leisure time compared with political duty and war at that era which is also
      similar in ancient China. From the leisure point of view, school should be relax
      and free for young children in kindergarten. This means that play should take the
      most time on the schedule. Unfortunately, Political class skillfully
      disseminating serious competition among nations to deliver anxiety on young
      generations' education to the public,which makes parents and school system highly
      valued formal learning much more than play. Chinese kindergarten may be have the
      longest formal learning time due to its history emphasis on learning from the
      model. Endure hardship as the basic habit from the younger children for the
      nature of life is full of hardship in Chinese philosophy. These underpinned ideas
      encounter great challenges from the Western early childhood education which puts
      more emphasis on play. Play is conceived as children's life itself, in which
      integrated learning can happen and is much more suitable and abundant for young
      children than formal learning. Although Chinese Educational Ministry promulgated
      kindergarten work regulation and educational guideline to make play as the basic
      activity in 1996 and 2001,there are still lots of factors that impede
      kindergartens implement play in practice. Lack of free time in kindergarten both
      on schedule and in fact is the obvious sign. This paper wants to reflect those
      factors in cultural perspective and try to use variety meanings of time
      especially subjective time to analysis the practice on reconstructing
      kindergartens' play atmosphere and time, and the findings on creating different
      inter-subjective time for young children.

PMID- 30117062
TI  - Anti PD-1 treatment increases [18F]FDG uptake by cancer cells in a mouse B16F10
      melanoma model.
AB  - BACKGROUND: Programmed cell death 1 (PD-1) inhibitors act as immune checkpoint
      inhibitors and are more effective for improving survival time with less toxicity
      as compared with conventional chemotherapies. In anti PD-1 therapy, it is
      important to evaluate metabolism in the cancer microenvironment, as this helps to
      clarify the pathological conditions. Herein, we investigate the early effects of
      PD-1 therapy on 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake in vivo,
      focusing on cell distribution and glycolysis in both cancer and immune cells.
      RESULTS: In a B16F10 melanoma model, [18F]FDG-positron emission tomography (PET)
      was performed before treatment and 7 days after the start of treatment. Values
      were calculated as the percentage-injected activity per gram of tissue (%IA/g).
      Flow-cytometry was then performed to assess immune cell populations and glucose
      metabolism. There was a negligible difference in [18F]FDG uptake between tumors
      in the treatment group and non-treatment group before the treatment. In contrast,
      mean [18F]FDG uptake in the treatment group tumors was significantly higher (8.06
      +/- 0.48 %IA/g; P = 0.0074) than that in the non-treatment group (4.02 +/- 1.03
      %IA/g) after anti PD-1 treatment. Assessment of tumor immune cell populations
      showed that treatment slightly enriched CD8+ T cells and CD4+ T cells; however,
      infiltration of immune cells was negligible, and thus, immune cells were not
      responsible for the increase in [18F]FDG uptake. On the other hand, anti PD-1
      treatment significantly increased glucose transporter 1 (GLUT1) and hexokinase II
      expression in CD45- cancer cells, indicating that anti PD-1 treatment increased
      glucose metabolism in cancer cells. CONCLUSION: The present study shows that anti
      PD-1 therapy increases glucose metabolism in cancer cells.

PMID- 30117063
TI  - On Female Genital Cutting: Factors to be Considered When Confronted With a
      Request to Re-infibulate.
AB  - According to the World Health Organization, female genital cutting affects
      millions of girls and women worldwide, particularly on the African continent and
      in the Middle East. This paper presents a plausible, albeit hypothetical,
      clinical vignette and then explores the legal landscape as well as the ethical
      landscape physicians should use to evaluate the adult patient who requests re
      infibulation. The principles of non-maleficence, beneficence, justice, and
      autonomy are considered for guidance, and physician conscientious objection to
      this procedure is discussed as well. Analyses of law and predominant principles
      of bioethics fail to yield a clear answer regarding performing female genital
      cutting or re-infibulation on an adult in the United States. Physicians should
      consider the patient's physical, mental, and social health when thinking about
      female genital cutting and should understand the deep-rooted cultural
      significance of the practice.

PMID- 30117064
TI  - Impossible "Choices": The Inherent Harms of Regulating Women's Testosterone in
      Sport.
AB  - In April 2018, the International Association of Athletics Federations (IAAF)
      released new regulations placing a ceiling on women athletes' natural
      testosterone levels to "ensure fair and meaningful competition." The regulations
      revise previous ones with the same intent. They require women with higher natural
      levels of testosterone and androgen sensitivity who compete in a set of
      "restricted" events to lower their testosterone levels to below a designated
      threshold. If they do not lower their testosterone, women may compete in the male
      category, in an intersex category, at the national level, or in unrestricted
      events. Women may also challenge the regulation, whether or not they have lowered
      their testosterone, or quit sport. Irrespective of IAAF's stated aims, the
      options forced by the new regulations are impossible choices. They violate
      dignity, threaten privacy, and mete out both suspicion and judgement on the sex
      and gender identity of the athletes regulated.

PMID- 30117065
TI  - Fluidic shear stress increases the anti-cancer effects of ROS-generating drugs in
      circulating tumor cells.
AB  - PURPOSE: Many anti-cancer drugs are used in chemotherapy; however, little is
      known about their efficacy against circulating tumor cells (CTCs). In this study,
      we investigated whether the pulsatile fluidic shear stress (SS) in human arteries
      can affect the efficacy of anti-cancer drugs. METHODS: Cancer cells were
      circulated in our microfluidic circulatory system, and their responses to drug
      and SS treatments were determined using various assays. Breast and cervical
      cancer cells that stably expressed apoptotic sensor proteins were used to
      determine apoptosis in real-time by fluorescence resonance energy transfer (FRET)
      based imaging microscopy. The occurrence of cell death in non-sensor cells were
      revealed by annexin V and propidium iodide staining. Cell viability was
      determined by MTT assay. Intracellular reactive oxygen species (ROS) levels were
      determined by staining cells with two ROS-detecting dyes: 2',7'
      dichlorofluorescin diacetate and dihydroethidium. RESULTS: Fluidic SS
      significantly increased the potency of the ROS-generating drugs doxorubicin (DOX)
      and cisplatin but had little effect on the non-ROS-generating drugs Taxol and
      etoposide. Co-treatment with SS and ROS-generating drugs dramatically elevated
      ROS levels in CTCs, while the addition of antioxidants abolished the pro
      apoptotic effects of DOX and cisplatin. More importantly, the synergistic killing
      effects of SS and DOX or cisplatin were confirmed in circulated lung, breast, and
      cervical cancer cells, some of which have a strong metastatic ability.
      CONCLUSIONS: These findings suggest that ROS-generating drugs are more potent
      than non-ROS-generating drugs for destroying CTCs under pulsatile fluidic
      conditions present in the bloodstream. This new information is highly valuable
      for developing novel therapies to eradicate CTCs in the circulation and prevent
      metastasis.

PMID- 30117066
TI  - Co-expressed genes enhance precision of receptor status identification in breast
      cancer patients.
AB  - PURPOSE: Therapeutic decisions in breast cancer patients crucially depend on the
      status of estrogen receptor, progesterone receptor and HER2, obtained by
      immunohistochemistry (IHC). These are known to be inaccurate sometimes, and we
      demonstrate how to use gene-expression to increase precision of receptor status.
      METHODS: We downloaded data from 3241 breast cancer patients out of 36 clinical
      studies. For each receptor, we modelled the mRNA expression of the receptor gene
      and a co-gene by logistic regression. For each patient, predictions from logistic
      regression were merged with information from IHC on a probabilistic basis to
      arrive at a fused prediction result. RESULTS: We introduce Sankey diagrams to
      visualize the step by step increase of precision as information is added from
      gene expression: IHC-estimates are qualified as 'confirmed', 'rejected' or
      'corrected'. Additionally, we introduce the category 'inconclusive' to spot those
      patients in need for additional assessments so as to increase diagnostic
      precision and safety. CONCLUSIONS: We demonstrate a sound mathematical basis for
      the fusion of information, even if partly contradictive. The concept is
      extendable to more than three sources of information, as particularly important
      for OMICS data. The overall number of undecidable cases is reduced as well as
      those assessed falsely. We outline how decision rules may be extended to also
      weigh consequences, being different in severity for false-positive and false
      negative assessments, respectively. The possible benefit is demonstrated by
      comparing the disease free survival between patients whose IHC could be confirmed
      versus those for which it was corrected.

PMID- 30117067
TI  - Comparison of titanium dioxide scaffold with commercial bone graft materials
      through micro-finite element modelling in flow perfusion.
AB  - TiO2 scaffolds have previously shown to have promising osteoconductive properties
      in previous in vivo experiments. Appropriate mechanical stimuli can further
      promote this osteoconductive behaviour. However, the complex mechanical
      environment and the mechanical stimuli enhancing bone regeneration for porous
      bioceramics have not yet been fully elucidated. This paper aims to compare and
      evaluate mechanical environment of TiO2 scaffold with three commercial CaP
      biomaterials, i.e. Bio-Oss, Cerabone and Maxresorb under simulated perfusion
      culture conditions. The solid phase and fluid phase were modelled as linear
      elastic material and Newtonian fluid, respectively. The mechanical stimulus was
      analysed within these porous scaffolds quantitatively. The results showed that
      the TiO2 had nearly heterogeneous stress distributions, however lower effective
      Young's modulus than Cerabone and Maxresorb. The permeability and wall shear
      stress (WSS) for the TiO2 scaffold was significantly higher than other commercial
      bone substitute materials. Maxresorb and Bio-Oss showed lowest permeability and
      local areas of very high WSS. The detailed description of the mechanical
      performance of these scaffolds could help researchers to predict cell behaviour
      and to select the most appropriate scaffold for different in vitro and in vivo
      performances. Graphical abstract Schematic representation of the establishment
      procedure. Take the establishment process of Cerabone as an example. Left shows a
      slice of micro-CT image from Cerabone, and 1.5 mm * 1.5 mm region of interest was
      shown in the red box. A 1.5-mm3 cube was cut out by Boolean operation in Mimics
      (Materialise, Belgium), and the cubic model was remeshed in 3-Matic 6.0
      (Materialise, Belgium). The cubic model is shown in blue, and the empty space in
      red.

PMID- 30117068
TI  - Automatic directional analysis of cell fluorescence images and morphological
      modeling of microfilaments.
AB  - Cytoskeleton and nucleus are two important anatomic components in eukaryotic
      cells. Cell fluorescence images are employed to study their realignment and
      deformation during cell extrusion. Quantitative analysis and modeling of cell
      orientation are investigated in this paper. For orientation measurement,
      alignment orientation of microfilaments is calculated using structure tensor
      method. Nuclei is segmented and fitted to ellipses in nuclei images. Based on the
      fitted ellipse, orientation and aspect ratio of each nucleus are computed. A
      morphological model is proposed to describe the movement of microfilaments
      quantitatively. The parameters of the model are determined by in-plane stresses
      obtained by numerical simulation. The proposed automatic orientation measurement
      algorithms can help to analyze the relationship between cell orientation and
      stress qualitatively. The proposed morphological model is the first model to
      quantitatively describe the relationship of microfilament movement with stress.
      Experimental results show that cell and nucleus tend to align along in-plane
      maximum shear stress and the proposed morphological model is a reasonable model
      for cell movement. The modeling of cell behavior under different stress can
      facilitate biomedical research such as tissue engineering and cancer analysis.
      Graphical abstract ?.

PMID- 30117069
TI  - Animal Pharmacokinetic/Pharmacodynamic Studies (APPS) Reporting Guidelines.
AB  - Animal pharmacokinetic/pharmacodynamic studies are commonly used to provide
      meaningful preclinical information that can be utilized by the scientific
      community to conduct first-in-human studies. Poor presentation and interpretation
      of the data limit study reproducibility, and may result in rejection when the
      study is submitted to a journal, leading to loss of time and resources at
      multiple levels. In addition, inconsistencies in reporting the results of animal
      studies may limit the ability to extrapolate the experimental findings to humans.
      A few guidelines have been published to make the reporting of animal studies
      consistent; however, strict implementation of these guidelines by authors,
      reviewers, and journal editors is still lacking. In an attempt to make the
      reporting of animal pharmacokinetic/pharmacodynamic studies consistent and
      improve the standard of reporting, this article provides guidelines that can be
      followed when submitting such studies to a journal. A detailed checklist, based
      on these guidelines, has been developed that can be used by the authors,
      reviewers, and editors to check if the required information is included in the
      manuscript. These guidelines can also be used for designing and performing such
      studies.

PMID- 30117070
TI  - All Along the Watchtower: a Case of Long QT Syndrome Misdiagnosis Secondary to
      Genetic Testing Misinterpretation.
AB  - Clinical genetics services continue to expand into diverse medical specialties.
      An ever-increasing number of non-genetics providers are independently ordering
      genetic tests, interpreting results, and at times, making diagnoses leading to
      patient care recommendations. Non-genetics healthcare providers can help increase
      patient access to these services, but a potential pitfall occurs when these
      providers either do not have adequate expertise with genetic variant
      interpretation or do not have access to multi-disciplinary teams including
      genetic counselors or clinical geneticists for advanced review. In the cardiology
      setting, variant misinterpretation can lead to misattribution of disease risk,
      unnecessary treatments or management, and potentially adverse psychosocial and
      financial effects. To address this, case reports and series are needed to
      highlight variant misinterpretation and misdiagnoses, including discussion of
      possible solutions and best practices for avoidance. This report details a child
      previously diagnosed with long QT syndrome type 4 by chromosomal microarray who
      was then subsequently managed for this disease by cardiac providers with
      insufficient expertise to critically review and question the genetic testing
      results. The patient was eventually referred to a pediatric electrophysiology
      team as part of a larger multidisciplinary cardiovascular genetics program,
      composed of specialist genetic counselors, cardiologists, and clinical
      geneticists. Advanced review and clinical evaluation raised concern about the
      initial genetic testing result and diagnosis. Complementary testing with a
      different modality to confirm or disconfirm the chromosome microarray result was
      performed, providing evidence that the original result reflected analytic error
      in the laboratory as well as interpretive error by the clinical geneticist and
      that the patient was misdiagnosed, and treated over the course of years, for long
      QT syndrome. This case shows the value of multidisciplinary teams caring for
      patients with inherited cardiovascular diseases.

PMID- 30117072
TI  - Introducing 'Simple Variable Selection (SVS) Approach' for Improving the
      Quantitative Accuracy of Chemometric Assisted Fluorimetric Estimations of Dilute
      Aqueous Mixtures.
AB  - Excitation emission matrix fluorescence (EEMF) spectroscopy is a multiparametric
      fluorescence technique where the fluorescence intensity of a fluorophore is a
      function of excitation wavelength, emission wavelength and its concentration. The
      manual analysis of large volume of highly correlated EEMF data sets towards
      developing a calibration model for quantifying each fluorophores present in
      multifluorophoric mixtures is a difficult and time-consuming task. Over the
      years, Partial least square (PLS) algorithm has found its application towards
      providing swift and efficient analyses of large volumes of highly correlated
      spectral data sets. The PLS assisted EEMF spectroscopy has been successfully used
      towards quantifying the fluorophores in multifluorophoric mixtures without
      involving any pre-separation. However, the accuracy and robustness of developed
      calibration model can be significantly improved provided PLS analysis is carried
      out on the analytically relevant EEMF spectral variables. In the present work, a
      variable selection method baptized as simple variable selection (SVS) approach is
      introduced that provides a simple and computationally economical means of
      identifying the useful spectral variables for subsequent PLS analysis. The
      proposed SVS approach is successfully validated by analyzing the complex EEMF
      data sets of multifluorophoric mixtures of consisting of multifluorophoric
      mixtures of biological relevance. The proposed approach is found to provide a
      simple, swift and efficient means for developing a robust PLS assisted EEMF
      spectroscopy based calibration model for simultaneous quantification of various
      fluorophores present in multifluorophoric mixtures.

PMID- 30117071
TI  - The Role of Diet in Multiple Sclerosis: Mechanistic Connections and Current
      Evidence.
AB  - PURPOSE OF REVIEW: This review seeks to examine current research related to the
      role of diet in multiple sclerosis (MS). RECENT FINDINGS: Recent research in
      preclinical models, epidemiologic studies, and limited prospectively followed
      cohorts provide preliminary evidence that dietary factors influence MS incidence,
      disease course, and symptomatology. Current evidence for the effects of fatty
      acids, fruits and vegetables, whole grains, dairy, and salt are reviewed. Dietary
      patterns including overall diet quality, caloric restriction, McDougall diet,
      Paleolithic diet, and Mediterranean diet are discussed. Hypotheses regarding
      potential mechanistic connections underlying observed effects are also presented.
      Several individual dietary components and patterns demonstrate potential for
      significant impact in MS. Definitive answers regarding the ability of diet to act
      as a disease modifier in MS will ultimately require large-scale clinical trials.
      Continued prospective studies and clinical trials to further advance this line of
      research are warranted.

PMID- 30117073
TI  - Rapid Antibiotic Susceptibility Determination for Yersinia pestis Using Flow
      Cytometry Spectral Intensity Ratio (SIR) Fluorescence Analysis.
AB  - Rapid antimicrobial susceptibility tests (ASTs) are essential tool for proper
      treatment of patients infected by Yersinia pestis (Y. pestis), the causative
      agent of plague, or for post-exposure prophylaxis of a population exposed to a
      naturally acquired or deliberately prepared resistant variant. The standard AST
      of Y. pestis is based on bacterial growth and requires 24-48 h of incubation in
      addition to the time required for prior isolation of a bacterial culture from the
      clinical or environmental sample, which may take an additional 24-48 h. In this
      study, we present a new and rapid AST method based on a fluorescence
      determination of the minimum inhibitory concentration (MIC). Our method includes
      the incubation of bacteria with an antibiotic, followed by staining of the
      bacteria with oxonol dye (SynaptoGreen C4/FM1-43), which enables the rapid
      detection of an antibiotic's effect on bacterial viability. We show that stained,
      non-viable bacteria exhibit a spectral redshift and an increase in fluorescence
      intensity compared to intact control bacteria. Based on these criteria, we
      developed a rapid flow cytometer measurement procedure and a unique spectral
      intensity ratio (SIR) analysis that enables determination of antibiotic
      susceptibility for Y. pestis within 6 h instead of the 24 to 48 h required for
      the standard AST. This new rapid determination of antibiotic susceptibility could
      be crucial for reducing mortality and preventing the spread of disease.

PMID- 30117074
TI  - Buprenorphine/Naloxone (Zubsolv(r)): A Review in Opioid Dependence.
AB  - A new sublingual buprenorphine/naloxone tablet (hereafter referred to as
      buprenorphine/naloxone; Zubsolv(r)), combining a long-acting partial u receptor
      agonist and an opioid antagonist, is approved for the treatment of opioid
      dependence in adults and adolescents aged > 15 years. This formulation has a
      higher bioavailability, better taste and faster sublingual dissolve time than a
      reference sublingual buprenorphine/naloxone tablet (Suboxone(r)), advantages that
      provide greater patient preference (potentially improving adherence) and
      importantly may reduce the risk of buprenorphine parenteral abuse by providing
      similar buprenorphine exposure at an ~ 30% lower dosage than reference
      buprenorphine/naloxone. In large phase III trials of up to 28 days,
      buprenorphine/naloxone was associated with high treatment retention rates during
      the induction and stabilization phases, and also reduced opioid craving and
      opioid withdrawal symptoms. Although noninferiority of buprenorphine/naloxone to
      sublingual buprenorphine tablet during the 2-day induction phase was only shown
      in one of the two similarly designed trials, pooled analyses confirmed that
      treatment retention rates were similar in the buprenorphine/naloxone and
      buprenorphine groups. Where evaluated, noninferiority of buprenorphine/naloxone
      to sublingual buprenorphine/naloxone film (only approved in the USA) was also
      demonstrated at 15 days in the stabilization phase. During the 24-week extension
      study, buprenorphine/naloxone maintenance therapy sustained improvements in
      opioid craving and addiction severity scores. Buprenorphine/naloxone was
      generally well tolerated, displaying a tolerability profile that was generally
      consistent with that seen with reference buprenorphine/naloxone. In conclusion,
      with potentially greater patient preference and a lower potential for parenteral
      buprenorphine abuse than reference buprenorphine/naloxone, buprenorphine/naloxone
      expands the treatment options available for adults and adolescent (aged > 15
      years) patients with opioid dependence.

PMID- 30117075
TI  - The role of autophagy in pulmonary hypertension: a double-edge sword.
AB  - Autophagy is a recycling process that degrades damaged or unneeded cellular
      components for renewal. Accumulating evidence suggests that dysregulation of
      autophagy is involved in pulmonary hypertension (PH). PH is a progressive disease
      characterized by persistent proliferation of apoptosis-resistant pulmonary
      vascular cells. However, reports on the role of autophagy in the development of
      PH are often conflicting. In this review, we discuss recent development in the
      field with emphasis on pulmonary arterial endothelial cells, pulmonary smooth
      muscle cells, right ventricular myocyte, as well as pharmacological strategies
      targeting the autophagic signaling pathway.

PMID- 30117076
TI  - Changes in Sexual Behavior and STI Diagnoses Among MSM Initiating PrEP in a
      Clinic Setting.
AB  - We examined changes in sexual behavior and sexually transmitted infection (STI)
      prevalence among 183 men who have sex with men (MSM) initiating pre-exposure
      prophylaxis (PrEP) at an STD Clinic in Seattle, WA. We used generalized
      estimating equations to measure changes in sexual behavior during PrEP use, and
      linked PrEP patient data with STI surveillance data to compare the prevalence of
      chlamydia, gonorrhea, and early syphilis in the periods prior to and during PrEP
      use. Reporting never using condoms in the prior 30 days increased (adjusted
      relative risk = 1.46; 95% confidence interval 1.13, 1.88) at 12 months after PrEP
      initiation compared to the initial PrEP visit. Reporting unknown status partners
      in the prior 30 days decreased at 12 months compared to the initial PrEP visit,
      but there was no change in number of sexual partners or reporting HIV-positive or
      HIV-negative partners. The percentage of patients diagnosed with any STI while
      using PrEP (49.2%) was higher than the percentage diagnosed in the 12 months
      prior to PrEP use (35.0%), likely driven in part by increased STI screening
      during PrEP use. Among MSM on PrEP, we observed decreases in condom use, and a
      higher prevalence of STIs during PrEP use compared to prior to PrEP initiation.

PMID- 30117077
TI  - Effects of a School-Based Intervention on Frequency and Quality of Adolescent
      Parent/Caregiver Sexuality Communication: Results from a Randomized-Controlled
      Trial in Uganda.
AB  - In a cluster-randomized trial conducted in 22 government secondary schools in
      Uganda, effects of a school-based intervention aimed at improving aspects of
      parent/caregiver-adolescent communication on sexuality were examined. The
      intervention comprised classroom-based education sessions, take home assignments
      for students to discuss with parents/caregivers and parenting workshops. Baseline
      and post intervention questionnaires were completed by students and by
      parents/caregivers. Effect estimates were significant for both students and
      parents/caregivers on sexuality communication frequency and quality, and for
      positive and negative attitudes towards sex-related communication, all in the
      desired direction with effect sizes ranging from 0.17 to 0.38. Effects on four
      sum scores related to general parenting proved significant only for
      parents'/caregivers' legitimacy with regard to rule setting (parents'/caregivers'
      reports only). These results suggest that in Uganda, using schools as gateways,
      parent/caregiver-adolescent communication can be improved through modification of
      existing school curricula, training teachers in learner-centred approaches and
      through mobilization and training of parents/caregivers.

PMID- 30117078
TI  - Suboptimal Retention in Care Among Recently Released Prisoners: Implications for
      Social Workers in HIV Primary Care.
AB  - Certain populations of people living with HIV (PLWH) are at greater risk for
      falling out of care, including PLWH with a history of incarceration. This is
      associated with increased risk of morbidity and mortality. In the current
      retrospective cohort study, we examined patient-level information for 340 PLWH
      who had transferred HIV care services from prison or from other community-based
      or private HIV primary care providers to a large urban HIV clinic in the
      southeastern United States. Results indicated that, compared to those
      transferring care from another community-based or private medical provider, PLWH
      transferring care from prison were significantly less likely to be retained in
      care than PLWH transferring care from other providers, even after controlling for
      other factors. HIV primary care social workers, who are trained to provide case
      management services, can help provide PLWH with a coordinated continuum of care
      that addresses the complex issues faced post-release.

PMID- 30117079
TI  - Correction to: Outcomes of a Behavioral Intervention for Sleep Disturbances in
      Children with Autism Spectrum Disorder.
AB  - The original version of this article unfortunately contained errors. The errors
      induced during the production process are corrected. The correct keywords,
      figures and tables are given below.

PMID- 30117080
TI  - Cost-effectiveness analysis of low versus high dose colistin in the treatment of
      multi-drug resistant pneumonia in Saudi Arabia.
AB  - Background Gram negative pathogens are increasingly resistant to commonly used
      first line antibiotics and colistin is in most cases the only medicine available.
      There is very limited information available comparing the effectiveness and costs
      of low versus high dose colistin with studies showing efficacy with both doses
      and with variable levels of adverse effects. The absence of a definite dosing
      strategy makes a model to compare low dose and high dose colistin invaluable in
      making decisions regarding the appropriate use of colistin. Objective This study
      was designed to evaluate the cost effectiveness of low versus high dose colistin
      in the treatment of Pneumonia caused by colistin-only sensitive gram negative
      bacteria from the perspective of a tertiary care hospital in Saudi Arabia.
      Setting 300-bed tertiary care hospital in Saudi Arabia. Method A retrospective
      review was conducted to compare the costs and outcomes of treatment of pneumonia
      with low versus high dose colistin. The model followed an average patient from
      initiation of treatment until clinical cure or failure. Main outcome measures The
      main outcomes were cure, nephrotoxicity, total direct costs per episode, cost per
      additional cure and cost per nephrotoxicity avoided. Results There was no
      significant difference between high and low dose colistin with regards to
      clinical cure (30% vs. 21%; p = 0.292). Significantly more patients experienced
      nephrotoxicity with high versus low dose colistin (30% vs. 8%; p = 0.004). With
      low dose colistin the incremental costs per nephrotoxicity avoided was SAR
      3056.28. One-way sensitivity analyses did not change the overall results.
      Conclusion Low dose was not inferior to high dose colistin in terms of clinical
      cure and had a lower incidence of nephrotoxicity resulting in significant cost
      avoidance.

PMID- 30117081
TI  - Pharmacodynamic model for beta-lactam regimens used in surgical prophylaxis:
      model-based evaluation of standard dosing regimens.
AB  - Background Continual evolution of resistance among bacteria against methods of
      surgical prophylaxis may make currently used beta-lactam regimens inadequate.
      Objective To re-evaluate beta-lactam regimens in surgical prophylaxis. Setting A
      pharmacodynamic Monte Carlo simulation (MCS) model based on a number of patients
      in China. Methods Pharmacodynamic profiling using Monte Carlo simulation up to 4
      hours postinfusion was conducted for standard-dose, short-term (0.5 h) and
      prolonged (2 to 4 h) infusions of ampicillin, cefazolin, cefotaxime, cefoxitin,
      cefuroxime, ertapenem, and piperacillin/tazobactam in adult patients with normal
      renal function. Microbiological data were incorporated. Cumulative fraction of
      response (CFR) was determined for each regimen against populations of S. aureus,
      coagulase-negative staphylococci and E. coli. The optimal CFR was defined as >=
      90% response. Main Outcome Measure Cumulative fractions of response of
      pharmacodynamic target attainment. Results During the first 2 hours postinfusion,
      piperacillin/tazobactam 3.375 g exhibited consistently optimal cumulative
      fractions against S. aureus, CoNS and E. coli. Ampicillin 2 g (2 h) also
      displayed optimal CFRs for S. aureus and E. coli but not for coagulase-negative
      staphylococci. Cefoxitin 2 g didnot achieve any optimal CFRs, even via 2-h
      prolonged infusion (maximum 72.8% CFR for S. aureus and 64.5% CFR for E. coli).
      Cefazolin 2 g (4 h) and cefuroxime 1.5 g (4 h) provided desired CFRs across 4 h
      postinfusion for S. aureus but provided poor CFRs for coagulase-negative
      staphylococci and E. coli. Only ertapenem 1 g for E. coli and S. aureus and
      cefotaxime 1 g for E. coli consistently yielded >= 90% CFRs for 4 hour
      postinfusion. Conclusions Certain dosing regimens may warrant adjustment for
      improved prevention efficiency and enhanced empirical antibiotic regimens for
      surgical prophylaxis.

PMID- 30117082
TI  - Effects of genetic polymorphisms of CYP2C19 on the pharmacokinetics of zolpidem.
AB  - Zolpidem is indicated for the short-term treatment of insomnia and it is
      predominantly metabolized by CYP3A4, and to a lesser extent by CYP2C19, CYP1A2,
      and CYP2C9. Therefore, we evaluated the effects of CYP2C19 genetic polymorphisms
      on the pharmacokinetics of zolpidem in healthy male subjects. Thirty-two male
      subjects were recruited and all subjects were classified into three groups
      according to their genotypes: CYP2C19EM (CYP2C19*1/*1, n = 12), CYP2C19IM
      (CYP2C19*1/*2 or *1/*3, n = 10), and CYP2C19PM (CYP2C19*2/*2, *2/*3 or *3/*3, n =
      10). The pharmacokinetic parameters of zolpidem were compared in three CYP2C19
      genotype groups after zolpidem administration with or without a CYP3A4 inhibitor
      at steady-state concentration. Plasma concentrations of zolpidem were determined
      up to 12 h after drug administration by liquid chromatography-tandem mass
      spectrometry method. The maximum plasma concentration (Cmax) differed, but mean
      total area under the plasma concentration-time curve (AUCinf), half-life (t1/2),
      and apparent oral clearance (CL/F) of zolpidem administered alone did not
      significantly differ among the three different CYP2C19 genotype groups.
      Furthermore, when zolpidem was administered with a CYP3A4 inhibitor at steady
      state concentration, there were no significant differences in any of the
      pharmacokinetic parameters of zolpidem in relation to CYP2C19 genotypes. In
      conclusion, we did not find any evidence for the impact of CYP2C19 genetic
      polymorphisms on the pharmacokinetic parameters of zolpidem.

PMID- 30117084
TI  - Non-explosivity of Stochastically Modeled Reaction Networks that are Complex
      Balanced.
AB  - We consider stochastically modeled reaction networks and prove that if a constant
      solution to the Kolmogorov forward equation decays fast enough relatively to the
      transition rates, then the model is non-explosive. In particular, complex
      balanced reaction networks are non-explosive.

PMID- 30117083
TI  - Paeoniflorin attenuates atRAL-induced oxidative stress, mitochondrial dysfunction
      and endoplasmic reticulum stress in retinal pigment epithelial cells via
      triggering Ca2+/CaMKII-dependent activation of AMPK.
AB  - Abnormal accumulation of the free-form all-trans-retinal (atRAL), a major
      intermediate of human visual cycle, is considered to be a key cause of retinal
      pigment epithelial (RPE) dysfunction in the pathogenesis of retinal degenerative
      diseases such as age-related macular degeneration (AMD). Paeoniflorin (PF), a
      monoterpene glucoside isolated from Paeonia lactiflora Pall., has been used in
      clinical treatment of retinal degenerative diseases in China for several years;
      however, the underlying mechanism remains unclear. The aim of this study is to
      investigate the protective effect of PF against atRAL toxicity in human ARPE-19
      cells and its molecular mechanism. The results of our study showed that the pre
      treatment of PF dose-dependently attenuated atRAL-induced cell injury by the
      reduction of Nox1/ROS-associated oxidative stress, mitochondrial dysfunction and
      GRP78-PERK-eIF2alpha-ATF4-CHOP-regulated endoplasmic reticulum (ER) stress in
      ARPE-19 cells. Additionally, our data showed that PF mainly exerted its activity
      via triggering calcium-calmodulin dependent protein kinase II (CaMKII)-mediated
      activation of AMP-activated protein kinase (AMPK). AMPK inhibition significantly
      reversed the protective effect of PF against atRAL toxicity in ARPE-19 cells.
      Overall, our findings provided the novel mechanism of PF protecting human RPE
      cells, which may prevent the progression of retinal degenerative diseases.

PMID- 30117085
TI  - Excessive daytime sleepiness in general hospital nurses: prevalence, correlates,
      and its association with adverse events.
AB  - OBJECTIVE: To investigate the prevalence and correlates of excessive daytime
      sleepiness (EDS) in a population of hospital nurses in South China as well as the
      influence of EDS on the occurrence of adverse events. METHODS: A total of 1102
      nurses working in a large medical center were invited to participate in this
      cross-sectional study (96.9% females, mean age 29.6 years). They all completed a
      self-reported questionnaire consisting of items on demographic variables,
      lifestyle factors, insomnia, anxiety, depression, and both work-related and sleep
      related characteristics. RESULTS: A total of 1048 nurses gave a valid response
      (response rate 95.1%). Among them, 169 (16.1%) reported EDS as defined as an
      Epworth Sleepiness Scale >= 14. Depression (adjusted odds ratio = 2.24, 95%
      confidence interval 1.51-3.31), anxiety (1.65; 1.02-2.67), insomnia (2.29; 1.56
      3.36), rotating shift work (1.98; 1.03-3.83), and low interest in work (1.74;
      1.01-2.99) were all independent risk factors of the occurrence of EDS. EDS is
      associated with the occurrence of adverse events after controlling for
      confounding factors (adjusted OR 1.83, CI 1.26 to 2.67). CONCLUSIONS: EDS was
      common among this relatively young and healthy nurse population in south China.
      There were clear associations between EDS and depression, anxiety, insomnia,
      rotating shift work, and low work-related interest. Furthermore, EDS was an
      independent risk factor in the occurrence of adverse events (AEs) in our
      subjects.

PMID- 30117086
TI  - Do Anti-Bullying Laws Reduce In-School Victimization, Fear-based Absenteeism, and
      Suicidality for Lesbian, Gay, Bisexual, and Questioning Youth?
AB  - Lesbian, gay, and bisexual youth are at heightened risk for bullying and other
      forms of in-school victimization. Anti-bullying laws are a potential policy
      mechanism for addressing this issue, yet there has been little investigation of
      the impact of such policies for this population using generalizable samples or
      quasi-experimental designs. The current study explores whether the presence of
      state anti-bullying laws predicts lower likelihood of bullying victimization,
      fear-based absenteeism, in-school threats or injury with a weapon, and
      suicidality for lesbian, gay, bisexual, and questioning high school students in
      the United States. Based on Youth Risk Behavior Survey data across 22 states from
      2005-2015, coupled with data about the presence of general and enumerated anti
      bullying laws that include sexual orientation as a protected class, this study
      analyzes this topic using a quasi-experimental design (linear difference-in
      difference models). The results indicate that lesbian, gay, bisexual, and
      questioning youth (particularly boys aged 15 or younger) experienced less
      bullying victimization in states with general or enumerated anti-bullying laws.
      There was modest evidence of a reduction in fear-based absenteeism among boys in
      states with such laws. However, there was little evidence of a relationship
      between such policies and in-school threats or injuries or suicidality. Further,
      lesbian, bisexual, and questioning girls' likelihood of victimization,
      absenteeism, or suicidality was generally not related to the presence of anti
      bullying laws. The results suggest that general and enumerated anti-bullying laws
      may help reduce bullying victimization for gay, bisexual, and questioning boys.

PMID- 30117087
TI  - Depressive Symptomology as a Moderator of Friend Selection and Influence on
      Substance Use Involvement: Estimates from Grades 6 to 12 in Six Longitudinal
      School-Based Social Networks.
AB  - Although the contributions of friend selection and friend influence to adolescent
      homophily on substance use behaviors has been of enduring research interest,
      moderators of these processes have received relatively little research attention.
      Identification of factors that dampen or amplify selection and influence on
      substance use behaviors is important for informing prevention efforts. Whereas
      prior research has examined adolescent drinking, smoking, and marijuana use, the
      current study examined whether friend selection and friend influence operated on
      substance use involvement, an indicator of problematic use, and whether
      depressive symptomology moderated these processes. In addition, it examined
      whether these relationships varied from grade 6 to 12. The study used a cohort
      sequential design in which three cohorts of youth (first surveyed in grades, 6,
      7, and 8) in six school-based longitudinal social networks were surveyed up to
      seven times, yielding N = 6817 adolescents (49% female). Stochastic actor
      oriented models were applied to test hypothesized relationships in the six
      networks, then results were synthesized in a meta-analysis. Depressive symptoms
      did not moderate selection or influence on substance use involvement at any grade
      level, but indirectly contributed to diffusion of substance use involvement
      through school networks via patterns of network ties. Research is needed on
      contextual factors, particularly in schools, that might account for when, if at
      all, depressive symptoms condition friend selection and influence on substance
      use.

PMID- 30117088
TI  - Plant centromeres: genetics, epigenetics and evolution.
AB  - The centromere is a functional locus of the chromosome responsible for chromatid
      cohesion and segregation in cell division. Usually, the centromeres can be
      distinguished from the remaining chromosomal regions either in structure, as they
      are heterochromatic constrictions that divide the chromosome in two arms, or in
      molecular constitution, as they have an exclusive H3 histone variant and specific
      DNA sequences. Besides being essential for genetic stability of eukaryotes,
      centromere is particularly interesting since it plays conserved roles but show
      high variability on organization and DNA composition. Centromeres are usually
      composed by satellite repeats and retrotransposons and the sequences can differ
      even among closely related species. Some unusual configurations containing single
      copy DNA were also described, including even some transcribed genes. In this
      review, we discuss molecular constitution, epigenetics and different types of
      centromere, with emphasis on plant centromeres. We also present recent advances
      about evolutionary processes involved in origin and differentiation of
      centromeres.

PMID- 30117090
TI  - Outcomes Following Resection of Hepatocellular Carcinoma in the Absence of
      Cirrhosis.
AB  - BACKGROUND: Hepatocellular carcinoma (HCC) occasionally occurs in non-cirrhotic
      patients; however, outcomes for these patients are not extensively documented.
      METHODS: We performed an institutional review of patients without cirrhosis who
      underwent resection for HCC. Clinical data were evaluated to identify factors
      impacting recurrence-free survival (RFS) and overall survival (OS). RESULTS:
      Forty-two patients underwent hepatectomy for HCC in the absence of cirrhosis over
      a 10-year period. Median follow-up was 22 months. For the entire cohort, 1-, 3-,
      and 5-year RFS was 62%, 42%, and 38% and 1-, 3-, and 5-year OS was 78%, 60%, and
      49%, respectively. On univariate analysis, RFS was significantly worse for
      patients with a disrupted/absent tumor capsule (p = 0.027), vascular invasion (p
      = 0.030), elevated alkaline phosphatase (p = 0.004), and tumor size > 10 cm (p =
      0.016). OS was significantly worse for patients with a disrupted/absent tumor
      capsule (p = 0.044), obesity (p = 0.036), and elevated alkaline phosphatase (p =
      0.007) with a trend towards decreased OS for tumor size > 10 cm (p = 0.07).
      CONCLUSIONS: Patients undergoing resection for HCC in the absence of cirrhosis
      have fairly high recurrence and modest survival rates. Pre-operative alkaline
      phosphatase, tumor size, tumor encapsulation, and vascular invasion are important
      prognostic factors.

PMID- 30117089
TI  - Recombinant human interferon regulatory factor-1 (IRF-1) protein expression and
      solubilisation study in Escherichia coli.
AB  - Interferon regulatory factor-1 (IRF-1) is a tumor suppressor gene, which encodes
      a mammalian transcription factor that serves various vital functions in a cell,
      such as cell cycle regulation, immunomodulation, and antiviral response. We
      report full-length human IRF-1 cDNA cloning and expression in E. coli/BL21 cells
      with complete solubilisation of recombinant protein. We cloned the gene by the RT
      PCR technique using ORF-specific primers followed by expression of recombinant
      IRF-1 in E. coli under GST fusion system. The profound expression of recombinant
      protein was observed after inducing with 0.5 mM IPTG for 3 h at 37  degrees C. We
      observed few degradation products of low molecular mass along with full-length
      fusion protein. We successfully minimized the formation of low molecular mass
      degradation products of GST-huIRF-1 protein at 16  degrees C. Simultaneously, we
      achieved the expression of recombinant protein in soluble fraction of E.
      coli/BL21 cells at 20  degrees C with higher yield, which is crucial to the study
      of the biological functions of any protein. We further confirmed it by the
      immunoblotting technique using anti-IRF-1 and anti-GST antibodies under the
      induction of E. coli cells harboring the IRF-1 recombinant plasmid after
      sonicated and fractioned fractions. This work will serve as a platform for
      characterizing the recombinant protein that may pave the way to understand
      molecular mechanism of tumour suppression caused by this molecule.

PMID- 30117091
TI  - Tumor Platinum Concentrations and Pathological Responses Following Cisplatin
      Containing Chemotherapy in Gastric Cancer Patients.
AB  - PURPOSE: There is a wide range in tumor response following preoperative
      chemotherapy in locally advanced gastric or gastroesophageal junction cancers. We
      investigated the relationship between tumor platinum levels and pathological
      responses in these patients. METHODS: Tumor and adjacent normal tissues were
      retrieved. Pathological responses were assessed per standard criteria. Tissue
      platinum concentrations were determined with high-performance liquid
      chromatography mass spectrometry. Platinum distribution in tissue components was
      evaluated with imaging mass cytometry. Collagen content was evaluated using
      trichrome staining. RESULTS: Surgical specimens from 10 patients were available.
      Surgery was performed at a median time of 49 days (range: 28-72) after the last
      cycle of chemotherapy. The mean platinum level in tumor tissue in patients with
      any response was significantly higher than in those with no response (893 +/- 460
      vs. 38.8 +/- 8.8 pg, P = 0.007), so was the collagen content (37.4 +/- 6.8 vs.
      11.5 +/- 8.6%, P < 0.05). Platinum preferentially bound to collagen. CONCLUSIONS:
      Platinum was detectable in surgical specimens up to 72 days after preoperative
      chemotherapy. Higher tumor platinum concentration correlated with improved
      pathological response. Collagen binding potentially explained the high
      interpatient variability in tumor platinum concentrations.

PMID- 30117092
TI  - Qualitative Study of Knowledge, Perception, and Behavior Related to Hypertension
      and Cardiovascular Disease Risk Reduction Among Hypertensive African-Americans in
      Urban Inner City of South Bronx, New York.
AB  - OBJECTIVE: To study the knowledge, perception, and behaviors among hypertensive
      African-Americans in South Bronx, New York, to elucidate any gaps that could
      explain their poor blood pressure control. METHODS: Cross-sectional qualitative
      study on African-American participants with essential hypertension, on single or
      combined oral antihypertensive regimen. Three focus groups were presented with
      open-ended questions on topics including cardiovascular disease knowledge,
      perception, and behaviors. A total of 18 data collection tools were used.
      Concepts formulated were categorized into dominant themes. A sample size of 21
      participants was attained based on the saturation point related to emerging
      common themes. RESULTS: Six dominant themes identified were unhealthy diet,
      stress, patient-physician relationship, medication non-compliance, decreased
      physical activity, and hypertension complications. The most dominant was
      unhealthy diet with self-identified barriers such as poor food selection, family
      tradition, economical cost, will-power, food taste, and accessibility to
      healthier food. Regarding medication adherence, participants recognized trust was
      a determining factor that has been negatively reinforced by previous experiences
      with their healthcare providers especially when they were not perceived as
      knowledgeable. Participants have also felt they have been influenced by historic
      events in their health decision-making process. CONCLUSIONS: The South Bronx
      African-American population has some feelings that are valid and not simply
      misconceptions. Some of them are historically related, gaps in knowledge
      influenced by culture and traditions, and barriers to healthy behaviors enhanced
      by economic status, lack of will-power, physical limitations, and stress from
      daily living. A physician partnership with this African-American community to
      improve trust, raise awareness, facilitate, and change in behavior that could
      help address blood pressure control and prevent cardiovascular disease.

PMID- 30117094
TI  - Metabolomic Assays of Postmortem Brain Extracts: Pitfalls in Extrapolation of
      Concentrations of Glucose and Amino Acids to Metabolic Dysregulation In Vivo in
      Neurological Diseases.
AB  - Glucose utilization is reduced in vulnerable brain regions affected by
      neurological disorders, especially Alzheimer's disease (AD), but the basis for
      abnormal glucose homeostasis is unknown. Studies of brain-bank human tissue have
      made major contributions to understanding complex aspects of neurological,
      psychiatric, and neurodegenerative diseases, but they are not appropriate for
      metabolomic analysis of labile metabolites because postmortem intervals between
      death and tissue freezing are much too long. Recent reports of postmortem brain
      glucose levels led to suggestions that AD patients may be hyperglycemic and that
      elevated brain glucose levels along with reduced glycolytic activity reveal
      abnormal glucose homeostasis before clinical symptoms become manifest. These
      conclusions are, however, questioned because virtually all brain glucose is
      consumed within minutes after death, followed by progressive increases in glucose
      and amino acid levels, presumably due to autolytic changes. To illustrate
      pitfalls in use of autopsy material for metabolomic assays of labile metabolites,
      data from living human brain are compared with those from autopsy samples, and
      metabolism at the onset of postmortem ischemia is compared with calculated
      glycolytic enzyme activities. Postmortem glucose levels range from extremely low
      to unrealistically high, precluding their extrapolation to living brain. Indirect
      evaluation of glycolytic enzyme activities in postmortem AD brain is not valid
      because the glucose and amino acid concentrations used in the calculations are
      not stable after death, and reported values are unrealistically high. Specific
      recommendations are provided for non-invasive longitudinal monitoring of brain
      metabolism and metabolite levels in patients with neurological diseases.

PMID- 30117095
TI  - Muscarinic Receptor Modulation of the Cerebellar Interpositus Nucleus In Vitro.
AB  - How the cerebellum carries out its functions is not clear, even for its
      established roles in motor control. In particular, little is known about how the
      cerebellar nuclei (CN) integrate their synaptic and neuromodulatory inputs to
      generate cerebellar output. CN neurons receive inhibitory inputs from Purkinje
      cells, excitatory inputs from mossy fibre and climbing fibre collaterals, as well
      as a variety of neuromodulatory inputs, including cholinergic inputs. In this
      study we tested how activation of acetylcholine receptors modulated firing rate,
      intrinsic properties and synaptic transmission in the CN. Using in vitro whole
      cell patch clamp recordings from neurons in the interpositus nucleus, the
      acetylcholine receptor agonist carbachol was shown to induce a short-term
      increase in firing rate, increase holding current and decrease input resistance
      of interpositus CN neurons. Carbachol also induced long-term depression of evoked
      inhibitory postsynaptic currents and a short-term depression of evoked excitatory
      postsynaptic currents. All effects were shown to be dependent upon muscarinic
      acetylcholine receptor activation. Overall, the present study has identified
      muscarinic receptor activation as a modulator of CN activity.

PMID- 30117093
TI  - Cholesterol-dependent cytolysins: from water-soluble state to membrane pore.
AB  - The cholesterol-dependent cytolysins (CDCs) are a family of bacterial toxins that
      are important virulence factors for a number of pathogenic Gram-positive
      bacterial species. CDCs are secreted as soluble, stable monomeric proteins that
      bind specifically to cholesterol-rich cell membranes, where they assemble into
      well-defined ring-shaped complexes of around 40 monomers. The complex then
      undergoes a concerted structural change, driving a large pore through the
      membrane, potentially lysing the target cell. Understanding the details of this
      process as the protein transitions from a discrete monomer to a complex, membrane
      spanning protein machine is an ongoing challenge. While many of the details have
      been revealed, there are still questions that remain unanswered. In this review,
      we present an overview of some of the key features of the structure and function
      of the CDCs, including the structure of the secreted monomers, the process of
      interaction with target membranes, and the transition from bound monomers to
      complete pores. Future directions in CDC research and the potential of CDCs as
      research tools will also be discussed.

PMID- 30117096
TI  - Interactions of Mexiletine with Novel Antiepileptic Drugs in the Maximal
      Electroshock Test in Mice: An Isobolographic Analysis.
AB  - The aim of the study was to evaluate precisely the type of interactions between
      mexiletine (an antiarrhythmic drug) and four new generation antiepileptic drugs:
      lamotrigine, oxcarbazepine, topiramate and pregabalin in the maximal electroshock
      test in mice (MES). The isobolographic analysis was used to assess the nature of
      interactions between the tested drugs. Total brain concentrations of
      antiepileptics were also measured to detect possible pharmacokinetic
      interactions. The results obtained indicated that the mixture of mexiletine and
      pregabalin at the fixed ratios of 1:1 and 3:1 led to supra-additive interaction
      in terms of seizure suppression, while the proportion of 1:3 occurred additive.
      Synergism was also demonstrated for the combination of mexiletine and topiramate
      in all three proportions. Combinations of mexiletine with lamotrigine and
      mexiletine with oxcarbazepine were found to be additive. Adverse-effect profiles
      of mexiletine, antiepileptics and drug combinations were evaluated in the chimney
      test (motor coordination) and step-through passive-avoidance task (long-term
      memory). Mexiletine and drug combinations did not impair long-term memory.
      Moreover, all combinations of mexiletine with lamotrigine, oxcarbazepine and
      topiramate had no significant effect on motor coordination. However, the results
      from the chimney test indicated that pregabalin, administered alone at its ED50
      dose from the MES-test, significantly impaired motor performance. Similar adverse
      effects were observed when mexiletine was co-administered with pregabalin at the
      fixed-dose ratio combinations of 1:1 and 1:3. However, reduction of pregabalin
      dose at the fixed ratio of 3:1 seems to prevent significant motor impairment. The
      results may indicate that mexiletine can be considered as an adjunctive drug in
      antiepileptic treatment, particularly in patients with concomitant cardiac
      arrhythmia.

PMID- 30117098
TI  - Mineralocorticoid Receptors, Neuroinflammation and Hypertensive Encephalopathy.
AB  - Worldwide, raised blood pressure is estimated to affect 35-40% of the adult
      population and is a main conditioning factor for cardiovascular diseases and
      stroke. Animal models of hypertension have provided great advances concerning the
      pathophysiology of human hypertension, as already shown for the
      deoxycorticosterone-salt treated rat, the Dahl-salt sensitive rat, the Zucker
      obese rat and the spontaneously hypertensive rat (SHR). SHR has been widely used
      to study abnormalities of the brain in chronic hypertension. This review
      summarises present and past evidence that in the SHR, hypertension causes
      hippocampal tissue damage which triggers a pro-inflammatory feedforward cascade
      affecting this vulnerable brain region. The cascade is driven by
      mineralocorticoid receptor (MR) activation responding to endogenous
      corticosterone rather than aldosterone. Increased MR expression is a generalised
      feature of the SHR which seems to support first the rise in blood pressure. Then
      oxidative stress caused by vasculopathy and hypoxia further increases MR
      activation in hippocampal neurons and glia cells, activates microglia activation
      and pro-inflammatory mediators, and down-regulates anti-inflammatory factors. In
      contrast to MR, involvement of the glucocorticoid receptor (GR) in SHR is less
      certain. GR showed normal expression levels and blockage with an antagonist
      failed to reduce blood pressure of SHR. The findings support the concept that
      MR:GR imbalance caused by vasculopathy causes a switch in MR function towards a
      proverbial "death" receptor.

PMID- 30117099
TI  - Echinosporin antibiotics isolated from Amycolatopsis strain and their antifungal
      activity against root-rot pathogens of the Panax notoginseng.
AB  - Actinomycete strain YIM PH20520, isolated from the rhizosphere soil sample of
      Panax notoginseng collected in Wenshang, Yunnan Province, China, exhibited
      antifungal activity against root-rot pathogens of the Panax notoginseng. The
      structures of bioactive molecules, isolated from the ethyl acetate extract of the
      fermentation broth of the strain, were identified as echinosporin (1) and 7
      deoxyechinosporin (2) based on extensive spectroscopic analyses. 1 exhibited
      antifungal activity against four tested root-rot pathogens of Panax notoginseng
      include Fusarium oxysporum, Fusarium solani, Alternaria panax, and Phoma herbarum
      with the MIC value at 64, 64, 32, and 64 MUg/mL, respectively. 2 exhibited
      antifungal activities against F. oxysporum, F. solani, A. panax, and P. herbarum
      with the MIC value at 128, 128, 64, and 128 MUg/mL, respectively. Based on the
      phylogenetic analyses, the closest phylogenetic relative of strain YIM PH20520 is
      Amycolatopsis speibonae JS72T (97.69%), so strain YIM PH20520 was identified as
      Amycolatopsis strain. To the best of our knowledge, this is the first report of
      echinosporin antibiotics isolated from Amycolatopsis strain besides Streptomyces
      strain and their antifungal activity against four tested root-rot pathogens of
      the Panax notoginseng. The results provide a reliable evidence for the following
      related biosynthetic investigations on Amycolatopsis strain YIM PH20520 due to
      echinosporins antibiotics' unique tricyclic acetal-lactone structures.

PMID- 30117101
TI  - Circulating leptin levels predict the decline in renal function with age in a
      sample of adult men (The Olivetti Heart Study).
AB  - Leptin (LPT) is associated with a number of cardiovascular risk factors, such as
      high blood pressure (BP), insulin resistance and excess in body weight. Some
      studies find an unfavorable cross-sectional association between LPT and renal
      disease, in particular in patients with already known kidney dysfunction. There
      are few data on the relationship between LPT and changes in renal function over
      time in subjects without evidence of kidney dysfunction. Hence, the aim of this
      study is to estimate the predictive role of LPT on the decline in renal function
      occurring in an 8-year follow-up observation of a sample of adult apparently
      healthy men (The Olivetti Heart Study). The study includes 319 untreated
      normotensive and nondiabetic men without clinical evidence of renal dysfunction
      (creatinine clearance-CrCl > 60 mL/min/1.73 m2) at baseline. At baseline, LPT is
      significantly and positively associated with BMI, abdominal circumference, BP and
      Homa index, no relationship is found with CrCl. At the end of the 8-year follow
      up, a significant association is detected between baseline LPT and changes
      occurring in BP. Moreover, an inverse correlation with changes in CrCl is found
      (r = - 0.12). This unfavorable relationship between baseline LPT and decline in
      renal function is also confirmed in the multivariate analyses, after adjustment
      for all potential confounders (R2 = 0.42, p < 0.01). The results of this
      prospective investigation suggest a predictive role of circulating LPT levels on
      decline in renal function over time, independently of main potential confounders,
      in normotensive and nondiabetic men with normal renal function at baseline.

PMID- 30117097
TI  - Mechanisms of Blood Brain Barrier Disruption by Different Types of Bacteria, and
      Bacterial-Host Interactions Facilitate the Bacterial Pathogen Invading the Brain.
AB  - This review aims to elucidate the different mechanisms of blood brain barrier
      (BBB) disruption that may occur due to invasion by different types of bacteria,
      as well as to show the bacteria-host interactions that assist the bacterial
      pathogen in invading the brain. For example, platelet-activating factor receptor
      (PAFR) is responsible for brain invasion during the adhesion of pneumococci to
      brain endothelial cells, which might lead to brain invasion. Additionally, the
      major adhesin of the pneumococcal pilus-1, RrgA is able to bind the BBB
      endothelial receptors: polymeric immunoglobulin receptor (pIgR) and platelet
      endothelial cell adhesion molecule (PECAM-1), thus leading to invasion of the
      brain. Moreover, Streptococcus pneumoniae choline binding protein A (CbpA)
      targets the common carboxy-terminal domain of the laminin receptor (LR)
      establishing initial contact with brain endothelium that might result in BBB
      invasion. Furthermore, BBB disruption may occur by S. pneumoniae penetration
      through increasing in pro-inflammatory markers and endothelial permeability. In
      contrast, adhesion, invasion, and translocation through or between endothelial
      cells can be done by S. pneumoniae without any disruption to the vascular
      endothelium, upon BBB penetration. Internalins (InlA and InlB) of Listeria
      monocytogenes interact with its cellular receptors E-cadherin and mesenchymal
      epithelial transition (MET) to facilitate invading the brain. L. monocytogenes
      species activate NF-kappaB in endothelial cells, encouraging the expression of P-
      and E-selectin, intercellular adhesion molecule 1 (ICAM-1), and Vascular cell
      adhesion protein 1 (VCAM-1), as well as IL-6 and IL-8 and monocyte
      chemoattractant protein-1 (MCP-1), all these markers assist in BBB disruption.
      Bacillus anthracis species interrupt both adherens junctions (AJs) and tight
      junctions (TJs), leading to BBB disruption. Brain microvascular endothelial cells
      (BMECs) permeability and BBB disruption are induced via interendothelial junction
      proteins reduction as well as up-regulation of IL-1alpha, IL-1beta, IL-6, TNF
      alpha, MCP-1, macrophage inflammatory proteins-1 alpha (MIP1alpha) markers in
      Staphylococcus aureus species. Streptococcus agalactiae or Group B Streptococcus
      toxins (GBS) enhance IL-8 and ICAM-1 as well as nitric oxide (NO) production from
      endothelial cells via the expression of inducible nitric oxide synthase (iNOS)
      enhancement, resulting in BBB disruption. While Gram-negative bacteria,
      Haemophilus influenza OmpP2 is able to target the common carboxy-terminal domain
      of LR to start initial interaction with brain endothelium, then invade the brain.
      H. influenza type b (HiB), can induce BBB permeability through TJ disruption. LR
      and PAFR binding sites have been recognized as common routes of CNS entrance by
      Neisseria meningitidis. N. meningitidis species also initiate binding to BMECs
      and induces AJs deformation, as well as inducing specific cleavage of the TJ
      component occludin through the release of host MMP-8. Escherichia coli bind to
      BMECs through LR, resulting in IL-6 and IL-8 release and iNOS production, as well
      as resulting in disassembly of TJs between endothelial cells, facilitating BBB
      disruption. Therefore, obtaining knowledge of BBB disruption by different types
      of bacterial species will provide a picture of how the bacteria enter the central
      nervous system (CNS) which might support the discovery of therapeutic strategies
      for each bacteria to control and manage infection.

PMID- 30117100
TI  - L-3-n-Butylphthalide reduces ischemic stroke injury and increases M2 microglial
      polarization.
AB  - Overwhelming evidence suggests that microglia play an important role in ischemic
      injury and they polarize into two different phenotypes with distinct functions
      after ischemic stroke. We performed the present study to investigate whether L-3
      n butylphthalide (NBP) has an effect on microglial polarization. Mice were
      subjected to transient middle cerebral artery occlusion (MCAO) for 45 min, and
      then immediately after reperfusion were treated with NBP or vehicle via the
      caudal vein for 7 consecutive days. 2,3,5-Triphenyltetrazolium chloride (TTC)
      staining showed that NBP treatment resulted in a tendency to decrease cerebral
      infarct volume at 1 day after MCAO, and significant decreased infarct volume at 3
      days after MCAO. Sensorimotor function was evaluated by the adhesive removal test
      and balance beam test, which were superior in NBP-treated mice compared with
      vehicle-treated mice at 1 and 3 days after MCAO. Immunofluorescent staining
      further indicated that NBP treatment significantly increased the number of
      CD206+/Iba1+ M2 microglia/macrophages and reduced the number of CD16+/Iba1+ M1
      cells at 3 and 7 days after MCAO reperfusion. Western blot also showed an
      elevation of M2 marker (arginase-1) in NBP-treated brains at 7 days after MCAO.
      In conclusion, our results clearly show that NBP treatment significantly
      mitigates ischemic brain damage and promotes recovery of neurological function in
      early phase after ischemic stroke, probably by skewing M1 microglia/macrophages
      polarization towards M2 phenotype. Thus, our study provides new evidence that NBP
      might be a promising candidate for ameliorating injury caused by ischemic stroke.

PMID- 30117102
TI  - The changing landscape of thromboprophylaxis for atrial fibrillation: insights
      from the ISPAF-2 survey.

PMID- 30117103
TI  - Targeting Axon Integrity to Prevent Chemotherapy-Induced Peripheral Neuropathy.
AB  - Chemotherapy-induced peripheral neuropathy (CIPN) is an irreversible off-target
      adverse effect of many chemotherapeutic agents such as paclitaxel, yet its
      mechanism is poorly understood and no preventative measure is available. CIPN is
      characterized by peripheral nerve damages resulting in permanent sensory function
      deficits. Our recent unbiased genome-wide analysis revealed that heat shock
      protein (Hsp) 27 is part of a transcriptional network induced by axonal injury
      and highly enriched for genes involved in adaptive neuronal responses,
      particularly axonal regeneration. To examine if Hsp27 could prevent the
      occurrence of CIPN, we first demonstrated that paclitaxel-induced allodynia was
      associated directly with axonal degeneration in sensory neurons in a mouse model
      of CIPN. We therefore hypothesize that by preventing axonal degeneration could
      prevent the development of CIPN. We drove expression of human Hsp27 (hHsp27)
      specifically in neurons. Development of mechanical and thermal allodynia was
      prevented completely in paclitaxel-treated hHsp27 transgenic mice. Strikingly,
      hHsp27 protected against paclitaxel-induced neurotoxicity in vivo including
      degeneration of afferent nerve fibers, demyelination, mitochondrial swelling,
      apoptosis, and restored sensory nerve action potential. Finally, we delineated
      signaling cascades that link CIPN development to caspase 3 and RhoA/cofilin
      activation in sensory neurons and peripheral nerves. hHsp27 exerted anti
      apoptotic effect and maintained axon integrity by restoring caspase 3 and RhoA
      expression to basal levels. Taken together, our data suggest that by preventing
      axonal degeneration might prove beneficial as anti-CIPN drugs, which represents
      an emerging research area for therapeutic development.

PMID- 30117105
TI  - Gintonin, a Ginseng-Derived Exogenous Lysophosphatidic Acid Receptor Ligand,
      Protects Astrocytes from Hypoxic and Re-oxygenation Stresses Through Stimulation
      of Astrocytic Glycogenolysis.
AB  - Astrocytes are a unique brain cell-storing glycogen and express lysophosphatidic
      acid (LPA) receptors. Gintonin is a ginseng-derived exogenous G protein-coupled
      LPA receptor ligand. Accumulating evidence shows that astrocytes serve as an
      energy supplier to neurons through astrocytic glycogenolysis under physiological
      and pathophysiological conditions. However, little is known about the
      relationships between LPA receptors and astrocytic glycogenolysis or about the
      roles of LPA receptors in hypoxia and re-oxygenation stresses. In the present
      study, we examined the functions of gintonin-mediated astrocytic glycogenolysis
      in adenosine triphosphate (ATP) production, glutamate uptake, and cell viability
      under normoxic, hypoxic, and re-oxygenation conditions. The application of
      gintonin or LPA to astrocytes induced glycogenolysis in concentration- and time
      dependent manners. The stimulation of gintonin-mediated astrocytic glycogenolysis
      was achieved through the LPA receptor-Galphaq/11 protein-phospholipase C-inositol
      1,4,5-trisphosphate receptor-intracellular calcium ([Ca2+]i) transient pathway.
      Gintonin treatment to astrocytes increased the phosphorylation of brain
      phosphorylase kinase, with sensitive manner to K252a, an inhibitor of
      phosphorylase kinase. Gintonin-mediated astrocytic glycogenolysis was blocked by
      isofagomine, a glycogen phosphorylase inhibitor. Gintonin additionally increased
      astrocytic glycogenolysis under hypoxic and re-oxygenation conditions. Moreover,
      gintonin increased ATP production, glutamate uptake, and cell viability under the
      hypoxic and re-oxygenation conditions. Collectively, we found that the gintonin
      mediated [Ca2+]i transients regulated by LPA receptors were coupled to astrocytic
      glycogenolysis and that stimulation of gintonin-mediated astrocytic
      glycogenolysis was coupled to ATP production and glutamate uptake under hypoxic
      and re-oxygenation conditions, ultimately protecting astrocytes. Hence, the
      gintonin-mediated astrocytic energy that is modulated via LPA receptors helps to
      protect astrocytes under hypoxia and re-oxygenation stresses.

PMID- 30117104
TI  - CD73 Downregulation Decreases In Vitro and In Vivo Glioblastoma Growth.
AB  - Glioblastoma is the worst and most common primary brain tumor. Here, we
      demonstrated the role of CD73, an enzyme responsible for adenosine (ADO)
      production, in glioblastoma progression. ADO increased glioma cell viability via
      A1 receptor sensitization. CD73 downregulation decreased glioma cell migration
      and invasion by reducing metalloproteinase-2 and vimentin expression and reduced
      cell proliferation by 40%, which was related to necrosis and sub-G1 phase
      blockage of cell cycle. Those effects also involved the stimulation of Akt/NF-kB
      pathways. Additionally, CD73 knockdown or enzyme inhibition potentiated
      temozolomide cytotoxic effect on glioma cells by decreasing the IC50 value and
      sensitizing cells to a non-cytotoxic drug concentration. CD73 inhibition also
      decreased in vivo rat glioblastoma progression. Delivery of siRNA-CD73 or APCP
      reduced tumor size by 45 and 40%, respectively, when compared with control. This
      effect was followed by a parallel 95% reduction of ADO levels in cerebrospinal
      fluid, indicating the role of extracellular ADO in in vivo glioma growth.
      Treatment did not induce systemic damage or mortality. Altogether, we conclude
      that CD73 is an interesting target for glioblastoma treatment and its inhibition
      may provide new opportunities to improve the treatment of brain tumors. Graphical
      Abstract ?.

PMID- 30117107
TI  - Critiquing the Concept of BCI Illiteracy.
AB  - Brain-computer interfaces (BCIs) are a form of technology that read a user's
      neural signals to perform a task, often with the aim of inferring user intention.
      They demonstrate potential in a wide range of clinical, commercial, and personal
      applications. But BCIs are not always simple to operate, and even with training
      some BCI users do not operate their systems as intended. Many researchers have
      described this phenomenon as "BCI illiteracy," and a body of research has emerged
      aiming to characterize, predict, and solve this perceived problem. However, BCI
      illiteracy is an inadequate concept for explaining difficulty that users face in
      operating BCI systems. BCI illiteracy is a methodologically weak concept;
      furthermore, it relies on the flawed assumption that BCI users possess
      physiological or functional traits that prevent proficient performance during BCI
      use. Alternative concepts to BCI illiteracy may offer better outcomes for
      prospective users and may avoid the conceptual pitfalls that BCI illiteracy
      brings to the BCI research process.

PMID- 30117106
TI  - Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation.
AB  - Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins
      in the healthy and diseased brain. As a result, there is a large body of evidence
      that associates BDNF with neuronal maintenance, neuronal survival, plasticity,
      and neurotransmitter regulation. Patients with psychiatric and neurodegenerative
      disorders often have reduced BDNF concentrations in their blood and brain. A
      current hypothesis suggests that these abnormal BDNF levels might be due to the
      chronic inflammatory state of the brain in certain disorders, as
      neuroinflammation is known to affect several BDNF-related signaling pathways.
      Activation of glia cells can induce an increase in the levels of pro- and
      antiinflammatory cytokines and reactive oxygen species, which can lead to the
      modulation of neuronal function and neurotoxicity observed in several brain
      pathologies. Understanding how neuroinflammation is involved in disorders of the
      brain, especially in the disease onset and progression, can be crucial for the
      development of new strategies of treatment. Despite the increasing evidence for
      the involvement of BDNF and neuroinflammation in brain disorders, there is scarce
      evidence that addresses the interaction between the neurotrophin and
      neuroinflammation in psychiatric and neurodegenerative diseases. This review
      focuses on the effect of acute and chronic inflammation on BDNF levels in the
      most common psychiatric and neurodegenerative disorders and aims to shed some
      light on the possible biological mechanisms that may influence this effect. In
      addition, this review will address the effect of behavior and pharmacological
      interventions on BDNF levels in these disorders.

PMID- 30117108
TI  - Biological activity of Claviceps gigantea in juvenile New Zealand rabbits.
AB  - The Ascomycete fungus Claviceps gigantea infects maize kernels and synthetizes
      several alkaloids, mostly dihydrolysergamides. There is limited information on
      the damage these toxins cause in mammals, despite reports from infested areas
      with 90% presence of the fungus sclerotia. With this background, it was decided
      to determine the biological activity of chemical compounds present in sclerotia
      of C. gigantea in rabbits 38 days after weaning. Sclerotia of C. gigantea were
      collected in fields with high incidence of the disease, ground and analysed for
      nutrients. Experimental diets were prepared with four treatments, where
      sclerotial powder was added, substituting for alfalfa flour in increasing
      proportions [C. gigantea/alfalfa flour (0:100, 5:95, 15:85 and 25:75)]. Total
      ergot alkaloid content was analysed by high-performance liquid chromatography.
      Male juvenile rabbits were utilised and distributed in completely randomised
      design with four replications. Initial weight was recorded in each animal, and
      experimental diet was offered. In this study, weight of animals, feed consumption
      and feed conversion were evaluated in individual animals. Blood samples were
      taken for haemograms, and finally euthanasia was practiced. The consumption of C.
      gigantea had a negative effect on body weight and feed consumption. The
      necropsies showed anomalies proportional to the consumption of feed contaminated
      with the fungus.

PMID- 30117109
TI  - Development of a UHPLC-FLD method for the analysis of ergot alkaloids and
      application to different types of cereals from Luxembourg.
AB  - Ergot alkaloids are toxins produced by some species of fungi in the genus
      Claviceps, that may infect rye and triticale and, in a minor degree, other types
      of cereals. In this study, a new UHPLC-FLD method for the quantification of the
      six major ergot alkaloids as well as their corresponding epimers was developed.
      The sample preparation was done by a solid-liquid extraction with acetonitrile
      and clean-up via freeze-out. The method was fully validated and then applied to
      39 samples (wheat, rye, triticale, and barley) harvested in Luxembourg in 2016.
      Samples were sieved (1.9 * 20 mm) prior to analysis in order to remove sclerotia,
      hosting the alkaloids. However, 23 samples still contained at least one ergot
      alkaloid > LOQ and concentrations of the sum of the 6 ergot alkaloids ranged from
      0.3 to 2530.1 MUg/kg. Interestingly, the highest concentrations were measured in
      wheat and not in rye or triticale, suggesting that all kinds of cereals should be
      included in monitoring programs. The outcome of this study allowed giving a first
      overview of ergot alkaloid concentrations in cereals harvested in Luxembourg, and
      the measured concentrations were in similar ranges than in other parts of the
      world (e.g., Canada, France, Germany).

PMID- 30117110
TI  - Enzyme Replacement Therapy During Pregnancy in Fabry Patients : Review of
      Published Cases of Live Births and a New Case of a Severely Affected Female with
      Fabry Disease and Pre-eclampsia Complicating Pregnancy.
AB  - Fabry disease (FD) is an X-linked, lysosomal storage disease. Mutations in the
      gene coding for alpha-galactosidase A lead to globotriaosylceramide (Gb-3)
      accumulation in lysosomes and in placenta and umbilical cord. Impact of FD and
      treatment with enzyme replacement (ERT) on foetal development is undisclosed.A 38
      year-old primigravida with FD (G85N) is reported. She has 50% reduced alpha
      galactosidase A activity and elevated plasma and urine-Gb-3. She was severely
      affected with ischaemic stroke at age 23, hypertension, albuminuria and
      moderately reduced renal function. ERT was initiated at age 23 years in 2001 and
      continued during spontaneous pregnancy at age 38. In third trimester she
      developed moderate-to-severe pre-eclampsia, successfully managed by methyldopa.
      Chorion villus sampling revealed a male foetus without the maternal gene
      mutation. Planned Caesarean section was performed without complications at
      gestational age week 38 + 6, delivering a healthy boy. Histopathological
      placental examination showed no sign of Gb-3 accumulation. Literature survey
      disclosed a total of 12 cases, 8 were treated with ERT during pregnancy and 5
      infants inherited the family mutation. All outcomes were successful. In the six
      cases with available placental histopathological examination, Gb-3 accumulation
      was only seen on the foetal side if the foetus had the inherited mutation.In
      conclusion, the present case, describing the first data from a severely affected
      FD patient receiving ERT during pregnancy complicated by pre-eclampsia, together
      with all other published cases, has emphasized that ERT is safe during pregnancy
      and resulting in successful foetal outcome; despite this, ERT is by the health
      authorities advised against during pregnancy.

PMID- 30117111
TI  - DPAGT1 Deficiency with Encephalopathy (DPAGT1-CDG): Clinical and Genetic
      Description of 11 New Patients.
AB  - Pathogenic mutations in DPAGT1 cause a rare type of a congenital disorder of
      glycosylation termed DPAGT1-CDG or, alternatively, a milder version with only
      myasthenia known as DPAGT1-CMS. Fourteen disease-causing mutations in 28 patients
      from 10 families have previously been reported to cause the systemic form, DPAGT1
      CDG. We here report on another 11 patients from 8 families and add 10 new
      mutations. Most patients have a very severe disease course, where common findings
      are pronounced muscular hypotonia, intractable epilepsy, global developmental
      delay/intellectual disability, and early death. We also present data on three
      affected females that are young adults and have a somewhat milder, stable
      disease. Our findings expand both the molecular and clinical knowledge of
      previously published data but also widen the phenotypic spectrum of DPAGT1-CDG.

PMID- 30117112
TI  - Cyst Masquerading as Inadvertent Bleb After a Scleral-Fixated Intraocular Lens in
      Marfan Syndrome: A Case Report.
AB  - INTRODUCTION: To present a case of an epithelial inclusion cyst masquerading as
      an inadvertent bleb in a patient with Marfan syndrome. CASE REPORT: A woman with
      Marfan syndrome presented with a subluxed crystalline lens in her right eye,
      which progressively subluxed over the following 2 years. A lensectomy was
      performed with placement of an anterior chamber intraocular lens (IOL); however,
      the patient experienced blurred vision and photopsias and preferred IOL
      explantation. The IOL was removed and a scleral-fixated posterior chamber IOL was
      placed. Vision improved with an uncomplicated postoperative course. Five months
      later, the patient experienced sudden onset redness and sharp pain in this eye. A
      3-mm cystic lesion with tan material was found over a prior scleral incision
      site. Intraocular pressure was normal and no aqueous leaked from the lesion.
      Owing to concerns of an infected inadvertent bleb, treatment with topical and
      oral antibiotics was started, but the lesion did not change in appearance and the
      patient experienced persistent pain. The lesion was surgically excised and
      histopathology revealed a conjunctival epithelial inclusion cyst with
      intralesional keratin. A month later, another conjunctival inclusion cyst
      developed and was excised per patient preference. CONCLUSION: Marfan syndrome is
      characterized by defects in the FBN1 gene and may theoretically lead to an
      abnormal sclera, increasing the risk of bleb formation after scleral incision.
      Distinguishing between a filtering bleb and an epithelial inclusion cyst is
      critical in patient care. Although retained keratin from a cyst may mimic a bleb
      with purulence, intraocular pressure, aqueous leakage, and response to topical
      antibiotics may help distinguish between the two.

PMID- 30117114
TI  - Most evidence for the compensation account of cognitive training is unreliable.
AB  - Cognitive training and brain stimulation studies have suggested that human
      cognition, primarily working memory and attention control processes, can be
      enhanced. Some authors claim that gains (i.e., post-test minus pretest scores)
      from such interventions are unevenly distributed among people. The magnification
      account (expressed by the evangelical "who has will more be given") predicts that
      the largest gains will be shown by the most cognitively efficient people, who
      will also be most effective in exploiting interventions. In contrast, the
      compensation account ("who has will less be given") predicts that such people
      already perform at ceiling, so interventions will yield the largest gains in the
      least cognitively efficient people. Evidence for this latter account comes from
      reported negative correlations between the pretest and the training/stimulation
      gain. In this paper, with the use of mathematical derivations and simulation
      methods, we show that such correlations are pure statistical artifacts caused by
      the widely known methodological error called "regression to the mean".
      Unfortunately, more advanced methods, such as alternative measures, linear
      models, and control groups do not guarantee correct assessment of the
      compensation effect either. The only correct method is to use direct modeling of
      correlations between latent true measures and gain. As to date no
      training/stimulation study has correctly used this method to provide evidence in
      favor of the compensation account, we must conclude that most (if not all) of the
      evidence should be considered inconclusive.

PMID- 30117115
TI  - Knowledge revision through the lenses of the three-pronged approach.
AB  - In the present study, we employed the three-pronged approach to determine the
      actual cognitive processes theorized in knowledge revision. First, the Knowledge
      Revision Components (KReC) framework was identified as the guiding theory.
      Second, think-aloud analysis highlighted at which points in refutation texts
      readers detected discrepancies between their incorrect, commonsense beliefs and
      the correct beliefs, and the exact processes with which they dealt with these
      discrepancies-successfully or unsuccessfully, as indicated by posttest scores.
      Third, corroborating reading-time data and posttest data demonstrated that the
      structure of the refutation texts facilitated the coactivation and integration of
      the explanation with the commonsense belief, resulting in knowledge revision.
      Finally, an analysis directly connected the processes identified during think
      aloud to sentence reading times. These findings systematically identify the
      cognitive processes theorized during knowledge revision and, in doing so, provide
      evidence for the conditions for revision outlined in the KReC framework.

PMID- 30117113
TI  - Berberine promotes glucose uptake and inhibits gluconeogenesis by inhibiting
      deacetylase SIRT3.
AB  - OBJECTIVE: Many studies have confirmed the glucose-lowering effect of berberine
      in type 2 diabetes patients. Although the mechanism of action of berberine
      involves the improvement of insulin sensitivity, its hypoglycemic mechanism
      remains elusive. Here we show a new mechanism by which berberine antagonizes
      glucagon signaling and find that SIRT3 is involved in the hypoglycemic effect of
      berberine. METHODS: Gene knockout and overexpression were used to assess the
      inhibitory effect of berberine on SIRT3. Downstream signaling pathways and the
      hypoglycemic effect of SIRT3 were evaluated by immunoblotting and metabolic
      monitoring. RESULTS: We found that berberine led to mitochondrial dysfunction and
      AMP accumulation by inhibiting deacetylase SIRT3. We confirmed that AMP
      accumulation activated the AMPK signaling pathway and further promoted glucose
      uptake. Simultaneously, AMP accumulation reduced cyclic AMP (cAMP) levels and
      abrogated the phosphorylation of critical protein targets of protein kinase A
      (PKA). Furthermore, we found that phosphoenolpyruvate carboxykinase 1 (PEPCK1) is
      a key gluconeogenesis enzyme that can be stabilized by glucagon. Berberine caused
      significant PEPCK1 ubiquitination and degradation by antagonizing glucagon and
      was accompanied by high levels of PEPCK1 acetylation. Interestingly, berberine
      induced glucagon inhibition is independent of AMPK activation. The in vivo data
      from sirt3 knockout mice were further confirmed by the in vitro experiments.
      CONCLUSIONS: Berberine promotes glucose uptake and inhibits gluconeogenesis by
      inhibiting SIRT3, and regulating mitochondria-related pathways may provide a
      novel approach to the development of antidiabetic drugs.

PMID- 30117116
TI  - Understanding and Identifying Key Issues with the Involvement of Clinicians in
      the Development of Decision-Analytic Model Structures: A Qualitative Study.
AB  - INTRODUCTION: Decision-analytic models play an essential role in informing
      healthcare resource allocation decisions; however, their value to decision makers
      will depend on model structures being clinically valid to determine cost
      effectiveness recommendations. Clinician involvement can help modellers to
      develop clinically valid but straightforward structures; however, there is little
      guidance available on methods for clinician input to model structure. This study
      aims to provide an in-depth exploration of clinician involvement in structural
      development, highlighting key issues and generating recommendations to optimise
      practices. METHODS: A qualitative study was undertaken with a range of modellers
      and clinicians working in different modelling contexts. In-depth interviews and
      case studies using observations were carried out to understand how clinicians are
      involved in model structural development and to identify problems and optimal
      approaches from informants' perspectives. RESULTS: Twenty-four interviews and two
      case studies were undertaken with modellers and modelling teams. Key issues
      included the number and diversity of clinicians contributing to structural
      development, potentially impacting the generalisability of structures, and
      problems with clinician understanding of important information to contribute to
      model pathways. Modellers and clinicians suggested that clinician training in
      modelling could enhance structural processes. CONCLUSIONS: Recommendations to
      optimise current practices include recruiting clinicians from a variety of
      backgrounds and using discussions between experts to develop valid and
      generalisable structures. Future research should focus on developing training
      materials for clinicians and finding ways to help modellers recruit clinicians
      from different settings.

PMID- 30117117
TI  - Author's Reply to Webster and Woollett: "The End of Phase 3 Clinical Trials in
      Biosimilars Development?"

PMID- 30117118
TI  - Comment on "The End of Phase 3 Clinical Trials in Biosimilars Development?"

PMID- 30117119
TI  - In vivo treatment of experimental neurocysticercosis with praziquantel
      nanosuspensions-a metabolic approach.
AB  - Neurocysticercosis is the most common parasitic infection of the nervous system
      and currently represents a serious public health issue in many regions of Latin
      America, Asia, and Africa. To date, praziquantel is one of the chosen drugs for
      the treatment of neurocysticercosis. Its mechanism of action is based on the
      inhibition of different biochemical pathways within the parasite which contribute
      to its death. Thus, the aim of this work was to analyze, for the first time,
      whether the nanoformulations of praziquantel would modify the energetic pathway
      of Taenia crassiceps cysticerci, after an intracranial inoculation in BALB/c
      mice. Praziquantel nanosuspensions were formulated with polyvinyl alcohol,
      poloxamer 188, and poloxamer 407, as stabilizers. These formulations exhibited
      particle size in a range of 74-285 nm and zeta potential values in a range of -
      8.1/- 13.2 depending on the type of stabilizer. Physical stability study at both
      4 +/- 2 and 25 +/- 2  degrees C indicated that praziquantel (PZQ) nanoparticles
      were stable in terms of solubility and particle size after 120-day storage. In
      vivo studies demonstrated that those nanosystems were able to produce significant
      modifications on the concentrations of oxaloacetate, citrate, pyruvate, alpha
      ketoglutarate, malate, succinate, lactate, beta-hydroxybutyrate, fumarate, and
      propionate involved in the metabolism of Taenia crassiceps cysticerci. Therefore,
      these nanoformulations may be considered as a promising tool to deliver
      praziquantel to the brain for the effective management of neurocysticercosis.

PMID- 30117120
TI  - Curcumin-loaded self-nanomicellizing solid dispersion system: part II: in vivo
      safety and efficacy assessment against behavior deficit in Alzheimer disease.
AB  - Curcumin (CUR), a natural polyphenolic compound, is considered as one of the most
      potential candidates against Alzheimer disease (AD) by targeting multiple
      pathologies such as amyloid-beta, tau phosphorylation, and oxidative stress. Poor
      physicochemical profile and oral bioavailability (BA) are the major contributors
      to its failure in clinical trials. Lack of success in numerous drug clinical
      trials for the treatment of AD urges the need of repositioning of CUR. To
      overcome its limitation and enhance oral BA, Novel CUR Formulation (NCF) was
      developed using self-nanomicellizing solid dispersion strategy which displayed
      117-fold enhancement in oral BA of CUR. NCF was tested using SH-SY5Y695 APP human
      neuroblastoma cell line against the cytotoxicity induced by copper metal ion,
      H2O2, and Abeta42 oligomer and compared with CUR control. The safety and efficacy
      of NCF on mice AD-like behavioral deficits (open field, novel objective
      recognition, Y-maze, and Morris water maze tests) were assessed in transgenic AD
      (APPSwe/PS1deE9) mice model. In SH-SY5Y695 APP human neuroblastoma cell line, NCF
      showed better safety and efficacy against the cytotoxicity due to the
      significantly enhancement of cellular uptake. It not only prevents the
      deterioration of cognitive functions of the aged APPSwe/PS1deE9 mice during aging
      but also reverses the cognitive functions to their much younger age which is also
      better than the currently available approved options. Moreover, NCF was proved as
      well tolerated with no appearance of any significant toxicity via oral
      administration. The results of the study demonstrated the potential of NCF to
      improve the efficacy of CUR without compromising its safety profile, and pave the
      way for clinical development for AD.

PMID- 30117122
TI  - Both 50 and 30 Hz continuous theta burst transcranial magnetic stimulation
      depresses the cerebellum.
AB  - The cerebellum is implicated in the pathophysiology of numerous movement
      disorders, which makes it an attractive target for noninvasive neurostimulation.
      Continuous theta burst stimulation (cTBS) can induce long lasting plastic changes
      in human brain; however, the efficacy of different simulation protocols has not
      been investigated at the cerebellum. Here, we compare a traditional 50-Hz and a
      modified 30-Hz cTBS protocols at modulating cerebellar activity in healthy
      subjects. Seventeen healthy adults participated in two testing sessions where
      they received either 50-Hz (cTBS50) or 30-Hz (cTBS30) cerebellar cTBS. Cerebellar
      brain inhibition (CBI), a measure of cerebello-thalamocortical pathway strength,
      and motor evoked potentials (MEP) were measured in the dominant first dorsal
      interosseous muscle before and after (up to ~ 40 min) cerebellar cTBS. Both cTBS
      protocols induced cerebellar depression, indicated by significant reductions in
      CBI (P < 0.001). No differences were found between protocols (cTBS50 and cTBS30)
      at any time point (P = 0.983). MEP amplitudes were not significantly different
      following either cTBS protocol (P = 0.130). The findings show cerebellar
      excitability to be equally depressed by 50-Hz and 30-Hz cTBS in heathy adults and
      support future work to explore the efficacy of different cerebellar cTBS
      protocols in movement disorder patients where cerebellar depression could provide
      therapeutic benefits.

PMID- 30117123
TI  - Successful hybrid treatment of a rare case of blunt traumatic rupture of the left
      atrial basal appendage and aortic arch.
AB  - Despite advances in emergency care and the emergent transportation system,
      cardiac and aortic ruptures after blunt trauma are associated with high mortality
      and morbidity. We present a rare case of a 70-year-old man with a ruptured left
      atrial basal appendage and distal aortic arch after sustaining blunt trauma to
      the chest during a motor vehicle accident. The patient was transported to our
      hospital in a state of shock and taken directly to the operating room. Hybrid
      treatment was performed, including surgical repair of the left atrium under
      cardiopulmonary bypass and thoracic endovascular aortic repair, was performed.
      The patient fully recovered without any complications.

PMID- 30117121
TI  - Chloroplast vesicle transport.
AB  - Photosynthesis is a well-known process that has been intensively investigated,
      but less is known about the biogenesis of the thylakoid membrane that harbors the
      photosynthetic machinery. Thylakoid membranes are constituted by several
      components, the major ones being proteins and lipids. However, neither of these
      two are produced in the thylakoid membranes themselves but are targeted there by
      different mechanisms. The interior of the chloroplast, the stroma, is an aqueous
      compartment that prevents spontaneous transport of single lipids and/or membrane
      proteins due to their hydrophobicities. Thylakoid targeted proteins are encoded
      either in the nucleus or plastid, and thus some cross the envelope membrane
      before entering one of the identified thylakoid targeting pathways. However, the
      pathway for all thylakoid proteins is not known. Lipids are produced at the
      envelope membrane and have been proposed to reach the thylakoid membrane by
      different means: invaginations of the envelope membrane, direct contact sites
      between these membranes, or through vesicles. Vesicles have been observed in
      chloroplasts but not much is yet known about the mechanism or regulation of their
      formation. The question of whether proteins can also make use of vesicles as one
      mechanism of transport remains to be answered. Here we discuss the presence of
      vesicles in chloroplasts and their potential role in transporting lipids and
      proteins. We additionally discuss what is known about the proteins involved in
      the vesicle transport and the gaps in knowledge that remain to be filled.

PMID- 30117125
TI  - Influenza and Influenza-Like Viruses: Frequent Infections in Children Under 14
      Years of Age During the 2016/2017 Epidemic Season.
AB  - Influenza is an infectious disease that is a common cause of infection among
      children. The main reason for it is the extremely low percentage of vaccinated
      people in Poland. In the 2016/2017 epidemic season more than 3,000 tests from
      children up to age 14 were examined. The dominance of subtype A/H3N2/ (40.9%) was
      confirmed. The evaluation was stratified by three age groups (0-4, 5-9, and 10-14
      years), which revealed significant differences. The highest number of samples was
      available in the 0-4 years group. The highest percentage of positive samples was
      present in the 10-14 years group. Influenza-like viral infections, among them the
      respiratory syncytial virus, were also observed. Children due to immature
      immunity are at particular risk for influenza. A lack of proper vaccination
      coverage strongly increases the chance of serious complications of the infection.

PMID- 30117124
TI  - Stonehenge technique is associated with faster aortic clamp time in group of
      minimally invasive aortic valve replacement via right infra-axillary thoracotomy.
AB  - BACKGROUND: Trans-right axillary aortic valve replacement (TAX-AVR) remains
      uncommon. We developed a special method to pull the heart closer to the right
      chest wall to make the surgery as easy and safe as aortic valve replacement via
      median sternotomy. Because the retraction sutures lifting the ascending aorta and
      aortic root are arranged circularly around the wound, we named this technique
      "Stonehenge technique". METHODS: We examined 47 patients who underwent aortic
      valve replacement through a small right infra-axillary thoracotomy as the initial
      surgical therapy. These patients were divided into two groups: the conventional
      TAX-AVR group that underwent AVR via the conventional small right axillary
      incision approach (n = 20) and the TAX-AVR with SH group that underwent AVR with
      the Stonehenge technique (n = 27). RESULTS: The aortic cross-clamp and the
      extracorporeal circulation time were significantly shorter in the TAX-AVR with SH
      group than in the conventional TAX-AVR group (conventional TAX-AVR group: 125.5
      +/- 47.9; TAX-AVR with SH group: 96.0 +/- 14.0, p = 0.004, and conventional TAX
      AVR group: 163.8 +/- 55.9; TAX-AVR with SH group: 140.0 +/- 16.8, p = 0.04).
      CONCLUSION: The outcomes of this technique depend on the site of the retraction
      sutures in the opened pericardium, direction of pull, amount of force applied,
      and precautions taken. If performed correctly, the ascending aorta and the root
      can be pulled from the wound to within the surgeon's fingers' reach, thereby
      reducing aortic cross-clamp and extracorporeal circulation times in group of
      minimally invasive aortic valve replacement via right infra-axillary thoracotomy.

PMID- 30117126
TI  - Vertebral artery dissection and golf swing: a paradigmatic new case.

PMID- 30117128
TI  - 3D echocardiographic imaging of an extremely rare rotation anomaly of the heart.

PMID- 30117127
TI  - Performance Enhancements in Differential Ion Mobility Spectrometry-Mass
      Spectrometry (DMS-MS) by Using a Modified CaptiveSpray Source.
AB  - Differential ion mobility spectrometry (DMS) spatially separates ions in the gas
      phase using the mobility differences of the ions under applied low and high
      electric fields. The use of DMS as an ion filter (or ion selector) prior to mass
      spectrometry analysis has been compromised by the limited ion transmission
      efficiency. This paper reports enhancement of the DMS-MS sensitivity and signal
      stability using a modified CaptiveSprayTM source. In terms of the ion sampling
      and transmission efficiency, the modified CaptiveSpray source swept ~ 89% of the
      ions generated by the tapered capillary through the DMS device (compared to ~ 10%
      with a conventional microspray source). The signal fluctuation improved from
      11.7% (relative standard deviation, RSD) with microspray DMS-MS to 3.6% using
      CaptiveSpray-DMS-MS. Coupling of LC to DMS-MS via the modified CaptiveSpray
      source was simple and robust. Using DMS as a noise-filtering device, LC-DMS-MS
      performed better than conventional LC-MS for analyzing a BSA digest standard.
      Although LC-DMS-MS had a lower sequence coverage (55%), a higher Mascot score
      (283) was obtained compared to those of LC-MS (sequence coverage 65%; Mascot
      score 192) under the same elution conditions. The improvement in the confidence
      of the search result was attributed to the preferential elimination of noise
      ions. Graphical Abstract ?.

PMID- 30117130
TI  - Conservative Management of Chronic Anal Fissure. Results of a Case Series at 2
      years Follow-up and Proposition of a New Classification.
AB  - BACKGROUND: Anal fissure is a common proctological condition that is usually
      defined as an anodermal ulcerative process starting from the posterior commissure
      to the dentate line. The objective of this study was to evaluate the resolution
      rate of anal fissure through the use of conservative management in patients
      grouped according to our newly proposed classification. A secondary purpose was
      to quantify the recurrence rates at 2-years follow-up in each group. METHODS: A
      retrospective analysis was carried out on patients in our general database.
      Diagnosis was based on symptoms, clinical observation, anal manometry and
      transanal ultrasounds. After application of inclusion and exclusion criteria,
      patients were assigned to different groups. Follow-up was carried out at 3, 6, 12
      and 24 months. RESULTS: A total of 136 patients (54 female and 82 male) were
      included in the statistical analysis. At the end of the treatment period, all
      patients in groups 1 and 2 had a complete resolution of illness and a normal
      basal sphincterial tone, while those in groups 3 and 4 had a higher rate of
      recurrence at the 2-year follow-up. CONCLUSION: Based on our series, we propose a
      definitive non-surgical management for all group 1 and 2 anal fissures according
      to our protocol. For groups 3 and 4, we recommend a primary non-surgical approach
      with follow-up. This was a retrospective study and further randomized controlled
      studies will be necessary to confirm our results.

PMID- 30117131
TI  - Extra-Thoracic Video-Assisted Thoracoscopic Surgery Rib Plating and Intra
      Thoracic VATS Decortication of Retained Hemothorax.
AB  - We report a patient who presented with multiple rib fractures after falling off a
      horse and was initially managed medically. Several weeks later, the patient
      returned to the hospital complaining of dyspnea on exertion. Physical exam
      revealed severe chest wall malformation and imaging revealed moderate hemothorax
      and complete collapse of the right lower lobe. Considering the likelihood that
      this patient's multiple ribs fractures contributed to the hemothorax and trapped
      lung, the patient underwent surgical evacuation of the hemothorax followed by rib
      fixation of ribs three through six. The procedures were performed using both
      intra-thoracic and extra-thoracic video-assisted thoracoscopic surgery (VATS) and
      did not require the use of thoracotomy incision or open exposure of the thoracic
      cavity. This case report suggests that this operative technique is a viable
      option for delayed presentation of multiple rib fractures and complex sequela
      associated with this pathology.

PMID- 30117129
TI  - Non-Compartmental Pharmacokinetics and Safety of Single-Dose Eldecalcitol (ED-71)
      in Healthy Chinese Adult Males.
AB  - BACKGROUND AND OBJECTIVES: Eldecalcitol (ED-71) is a novel active vitamin D3
      derivative, used for the treatment of osteoporosis. This is the first clinical
      study to investigate the pharmacokinetics and safety of eldecalcitol in Chinese
      subjects. METHODS: This was an open, single-center, randomized, two-dose level,
      two-period crossover phase I study in 24 healthy Chinese adult males. Eligible
      subjects received a single oral dose of eldecalcitol capsule 0.5 or 0.75 MUg at
      period 1 or period 2, monitored over a 144-h observation period for
      pharmacokinetics and a 14-day observation period for safety. The wash-out time
      was 14 days. The data observed in this study were compared with historical data
      in Japanese subjects to evaluate the inter-ethnic differences in
      pharmacokinetics. RESULTS: After single doses of 0.5 and 0.75 MUg eldecalcitol,
      the maximum serum concentration (Cmax) of eldecalcitol was reached within 3.0-4.0
      h (Cmax was 0.0638 +/- 0.0076 ng/ml in the 0.5-MUg group and 0.0944 +/- 0.0126
      ng/ml in the 0.75-MUg group, area under the concentration-time curve from 0 to 24
      h (AUC(0-24h)) was 1.02 +/- 0.15 ng.h/mL in the 0.5-MUg group and 1.57 +/- 0.26
      ng.h/mL in the 0.75-MUg group). The pharmacokinetic parameters was similar
      between the Chinese and Japanese subjects; both Cmax and partial AUCs could be
      considered to be dose-proportional over the tested dose range of 0.5-0.75 ug in
      Chinese subjects, which was in line with previously published results on
      eldecalcitol linear pharmacokinetics (range 0.1-1.0 ug) in Japanese subjects.
      Alanine aminotransferase increase was the most common adverse event (AE). No drug
      related serious AEs were reported. All of the drug-related AEs of eldecalcitol
      were mild in severity. CONCLUSION: Pharmacokinetic exposure (Cmax and partial
      AUCs) was dose-proportional over the tested dose range of 0.5-0.75 ug in healthy
      Chinese adult males. The pharmacokinetic character of eldecalcitol in Chinese
      subjects was similar to historical data from Japanese subjects. Eldecalcitol was
      well tolerated at doses ranging from 0.5 to 0.75 ug, with no new safety signals
      identified. CLINICAL TRIAL REGISTRATION: This study was registered at the China
      Food and Drug Administration (Registration number: 2014L02212 and 2014L02213),
      and also registered at http://www.chinadrugtrials.org.cn (No. CTR20160430).

PMID- 30117132
TI  - Intra-Operative Ultrasound: Tips and Tricks for Making the Most in Neurosurgery.
AB  - PURPOSE: Advances in intraoperative imaging and neuronavigation techniques have
      positively affected glioma surgery. The desire to reduce brain-shift-related
      problems while achieving the real-time identification of lesions and residual and
      anatomical relationships has strongly supported the introduction of
      intraoperative ultrasound (ioUS) in neuro-oncological surgery. This paper
      presents tips based on our experience with ioUS in neurosurgery. METHODS: We
      retrospectively analyzed 264 patients who underwent high-grade glioma (HGG)
      resection at the University of Turin and 60 patients who were treated at the
      University of Rome. RESULTS: The main issues are the correct choice of the probe
      and how to evaluate the anatomy to understand how the information from the three
      common US planes (axial, sagittal and coronal plane) can be used in each case. It
      is also important to correctly identify anatomical structures in ioUS imaging. In
      a normal brain, the sulci, sickle, tentorium, choroid plexus, ependyma and the
      walls of the vessels are all hyperechoic. In addition, some structures are
      hypoechoic with a homogeneous acoustic gradient: ventricles, cysts and everything
      that contains liquor. Tumors are usually hyperechoic in ioUS because of their
      higher cellularity. Conversely, acute edema that contains fluid is hypoechoic,
      while chronic edema is hyperechoic. CONCLUSIONS: IoUS is a real-time, accurate
      and inexpensive imaging method. The difficulties of interpretation can be
      overcome by experience in US imaging and a better understanding of the
      interaction between navigation and imaging fusion techniques. Training on a large
      number of cases is important for the correct assessment of ioUS information to
      obtain valuable, real-time information during HGG surgery.

PMID- 30117133
TI  - Effects of Coronal Limb Alignment and Ligament Balance on Pain and Satisfaction
      Following Total Knee Arthroplasty at Short-Term Follow Up.
AB  - INTRODUCTION: Few studies have evaluated the concomitant effect of both total
      knee arthroplasty (TKA) limb alignment and ligament laxity. Therefore, the
      primary aim of this study is to evaluate the impact of lower extremity alignment
      on the short-term outcome (one year) following TKA, including pain relief,
      function, and patient satisfaction. The secondary aim of the study is to evaluate
      the impact of ligament laxity and balance on early outcomes following TKA.
      MATERIALS AND METHODS: A prospective evaluation of mechanical alignment and
      ligament tension was performed for 110 consecutive TKAs using an identical
      surgical technique. Patients were evaluated with knee society score, visual
      analog pain score, and satisfaction one year following TKA. Linear regression
      analysis was then performed to determine the effect of lower extremity alignment
      and ligament laxity. RESULTS: There was no significant relationship between lower
      extremity alignment and outcome measures. A significant relationship was
      identified between medial collateral laxity in full extension and knee society
      scores for function, but not for pain. There was also a significant relationship
      identified between lateral knee laxity at 90 degrees of flexion and knee society
      score and pain at one-year follow up. CONCLUSION: Our results demonstrated no
      correlation between mechanical alignment restoration and pain or function.
      However, more interestingly, this study found patients with medial laxity in
      extension and lateral laxity in knee flexion, similar to normal physiologic knee
      laxity, to have less pain and greater function and satisfaction at one-year short
      term follow up.

PMID- 30117134
TI  - Mid- and Long-Term Outcome of Currently Available Endografts for the Treatment of
      Infrarenal Abdominal Aortic Aneurysm.
AB  - Currently, there is a wide range of commercially available endografts for
      infrarenal abdominal aortic aneurysm (AAA) repair. Results of long-term follow up
      after endovascular aneurysm repair (EVAR) are limited. Thereby, the durability of
      these endografts and the difference between manufacturers is not fully clear. In
      this review, studies with mid- and long-term results, with a minimum median
      follow up of 36 months per endograft, were included describing results with Cook
      Zenith? Flex? endograft (Cook Medical Inc., Bloomington, Indiana) (n=6), Cordis
      Corporate INCRAFT? (Cordis Corporation, Freemont, California) (n=1), Gore?
      EXCLUDER? (W.L. Gore & Associates Inc., Flagstaff, Arizona) (n=3), Medtronic
      Endurant? (Medtronic plc, Santa Rosa, California) (n= 6), and Vascutek Anaconda?
      (Vascutek Ltd., Inchinnan, Scotland) (n=2). The assisted technical success varied
      between 83% and 100%, and the perioperative mortality, early reintervention, and
      early conversion rates were comparable for the studied endografts. At three-year
      follow up, the freedom from AAA-rupture and AAA-related death varied between 98%
      and 100%. The results demonstrated an increasing complication and reintervention
      rate over time. When adhering to the instruction for use, minor differences were
      seen during follow up between the endografts. Latest generation endografts
      continue to have good postoperative results, the reintervention-rate of 10-20%
      over time mandates an ongoing close patient follow up. The choice of a specific
      design depends on native patient anatomy and the experience of the implanting
      surgeon.

PMID- 30117135
TI  - Step-by-step Illustration of the Cranial Bifrontal Approach.
AB  - Based on experience with several hundreds of adult and pediatric patients in whom
      the cranial bifrontal approach was used to achieve different surgical objectives,
      this paper describes this approach in a step-by-step manner with illustrations.
      This is a basic approach to the anterior cranial fossa that enables the
      preservation of most bridging veins. The bifrontal approach, whether basal,
      interhemispheric, or both, allows a wider bilateral operative field with better
      orientation and views of important neural structures and perforating arteries,
      without needing to be combined with other approaches. The following description
      should be regarded as a basic technique to arrive at a definite location within
      the anterior cranial compartment and beyond, rather than as rigid steps that must
      be followed rigorously. These illustrations are intended to present essential
      principles of a standard bifrontal approach. Since the same principles can be
      followed for every bifrontal approach, this technique along with the surgical
      results can be constantly improved.

PMID- 30117136
TI  - Initial Experience with Robotic Hernia Repairs: A Review of 150 Cases.
AB  - BACKGROUND: Robotic-assisted surgery has proved to be a valuable modality in
      specialties such as urology and gynecology and has gained wide acceptance in
      those fields. Its value in general surgery, however, has had a slower acceptance
      rate among surgeons. This study reviews my first 150 cases using the robot for
      one of the most common general surgery operations-the repair of hernias.
      MATERIALS AND METHODS: All robotic hernia cases performed by a single surgeon
      were documented in an Excel? (Microsoft Corporation, Redmond, Washington)
      spreadsheet beginning in April, 2014. Data recorded included patient diagnosis,
      hernia defect size, mesh type and size, console time and total operative time, as
      well as first assistant (fellow, resident, or none). The postoperative course was
      carefully reviewed through the electronic medical record to identify
      complications and readmissions. RESULTS: The average total case time was 138
      minutes, while the average console time was 100 minutes. Incisional hernias made
      up 50.4% of the procedures, inguinal hernias-17.2%, ventral/umbilical-9.8%,
      parastomal-9.2%, lumbar-5.5%, hiatal-4.9%, and spigelian-2.5%. The average defect
      size was 48.47cm2. Complication rates were low at 5.3%, most of which were minor.
      There were no mortalities. There has been one known hernia recurrence.
      CONCLUSIONS: This review shows that the use of the robot has proven to be safe
      and effective, and it has many benefits in hernia repair. One of those benefits
      is the ability to close the fascial defect with a running suture, thus avoiding
      the postoperative pain associated with transfascial sutures. The ability to
      intracorporeally fix a large piece of mesh to the abdominal wall that adequately
      and evenly covers the defect is another benefit. The high-quality three
      dimensional view and the ability to articulate the instruments are well
      established benefits of the robot as well. Robotic assistance also allows us to
      perform a minimally invasive hernia repair on large complex defects that would
      have otherwise been performed via an open approach.

PMID- 30117137
TI  - A Retrospective Comparative Analysis of 2D Versus 3D Laparoscopy in Total
      Laparoscopic Hysterectomy for Large Uteri (>= 500g).
AB  - STUDY OBJECTIVE: To evaluate the outcomes of total laparoscopic hysterectomy
      using 3D vision in comparison with 2D vision in women with large uteri (>=500g).
      DESIGN: Retrospective analytical study Design Classification: Canadian Task Force
      II-1 Setting: Tertiary referral center for advanced gynecological surgery.
      PATIENTS: Five hundred forty six women who underwent total laparoscopic
      hysterectomy over a period of 13 years were studied: 301 under 2D vision and 245
      under 3D vision. INTERVENTIONS: Total laparoscopic hysterectomy Measurements:
      Surgical time, blood loss and complications were recorded for every case in both
      groups. MAIN RESULTS: The duration of surgery for hysterectomy in the 3D
      laparoscopy group (88.01?36.95 min) was significantly shorter than that in the 2D
      group (112.61?42.59 min, p=.0001). Blood loss in the 500-1000g group was
      significantly less in the 3D group (p=.005). The total complication rates for 3D
      surgery (3.37 %) and 2D surgery (6.64%) were comparable (p=.25). CONCLUSION:
      Three-dimensional laparoscopy provides stereoscopic vision and increases
      precision and safety. The availability of depth perception adds to the ease of
      surgery, especially in cases of large uteri, leading to reductions in both the
      duration of surgery and blood loss, which improves patient outcomes.

PMID- 30117138
TI  - Endometrial Ablation: Past, Present, and Future Part II.
AB  - Endometrial ablation (EA) is the most commonly performed surgical procedure for
      the management of abnormal uterine bleeding unresponsive to medical therapy. In
      well-selected subjects, EA provides a safe, inexpensive, and convenient
      alternative to hysterectomy with a rapid return to normal function. The first
      generation of EA techniques were introduced in 1886 by Professor Sneguireff of
      Moscow. He was the first to apply super-heated steam to the uterine cavity to
      vaporize the endometrial basalis. This method-known as atmocausis-was refined by
      Ludwig Pincus of Danzig in 1895, and he went on to perform over 800 procedures.
      As the 20th century brought forth other energy sources-electricity, X-ray,
      radium, and even cryogenics-they were each used, in turn, to accomplish
      endometrial ablation. In 1981, Dr. Milton Goldrath successfully performed EA by
      co-locating a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser with a rod
      lens hysteroscope to achieve photovaporization of the endometrium. The
      accomplishment of EA under direct visualization defined the second generation of
      EA. The challenges and risks of second-generation technology, however, was soon
      apparent, and though this practice continues today, it appears to be confined to
      a relatively small number of devoted and highly-skilled sub-specialists. The late
      1990s saw increasing interest in safe, affordable, and easily-mastered EA
      technology. The result was a return to blind technology but modified with a
      variety of features that brought unprecedented safety to EA, even permitting its
      selected in-office application. This third generation of EA techniques and
      devices has propelled the growth of EA in the 21st century. Although much has
      been accomplished in the quest for safe, affordable, convenient, and easily
      mastered EA, the future requires refinement of patient selection criteria,
      management strategies for late-onset endometrial ablation failures (LOEAFs), as
      well as minimally invasive methods for reducing them.

PMID- 30117140
TI  - Efficacy and safety of daylight photodynamic therapy after tailored pretreatment
      with ablative fractional laser or microdermabrasion: a randomized, side-by-side,
      single-blind trial in patients with actinic keratosis and large-area field
      cancerization.
AB  - BACKGROUND: Physical pretreatments can potentiate the efficacy of daylight
      photodynamic therapy (dPDT), but clinical comparative studies remain limited.
      OBJECTIVES: Performed in large skin areas with actinic keratoses (AKs) and
      photodamage, this blinded, randomized clinical trial compared the efficacy and
      safety of dPDT after tailored skin pretreatment using ablative fractional laser
      (AFL) or microdermabrasion (MD). METHODS: Two >= 50-cm2 side-by-side skin areas
      were randomized to receive a single treatment with AFL-dPDT or MD-dPDT.
      Pretreatment parameters were tailored according to AK grade and skin constitution
      to ensure standardized immediate end points. Subsequently, methyl
      aminolaevulinate was applied, followed by 2-h daylight exposure. The primary
      outcome comprised blinded assessment of AK clearance at the 3-month follow-up.
      RESULTS: In 18 patients with 832 AKs, AFL-dPDT provided significantly higher AK
      clearance (81% vs. 60%, P < 0.001), led to fewer new AKs (P < 0.001) and showed
      superior improvement in dyspigmentation (P = 0.003) and skin texture (P = 0.001)
      vs. MD-dPDT. Peaking at days 3-6, AFL-PDT induced more intensified local skin
      responses (P = 0.004), including instances of Staphylococcus aureus infection (n
      = 3). Patients nonetheless preferred AFL-dPDT (P = 0.077), due to lower
      pretreatment-related pain (P = 0.002) and superior cosmesis (P = 0.035) and
      efficacy compared with MD-dPDT. CONCLUSIONS: AFL-dPDT is an effective treatment
      for patients with AK with extensive field cancerization, although AFL
      pretreatment is associated with intensified local skin reactions.

PMID- 30117141
TI  - Hormonal, stem cell and Notch signalling as possible mechanisms of disease in
      hidradenitis suppurativa: a systems-level transcriptomic analysis.

PMID- 30117139
TI  - Autoimmune cytopenias in patients with chronic lymphocytic leukaemia treated with
      ibrutinib in routine clinical practice at an academic medical centre.
AB  - The effects of ibrutinib on the natural history of autoimmune cytopenias (AIC)
      among chronic lymphocytic leukaemia (CLL) patients treated in routine clinical
      practice require further investigation. Using the Mayo Clinical CLL Database, 193
      CLL patients treated with ibrutinib between November 2013 and January 2017
      outside the context of a clinical trial were identified; complete review of their
      medical records was performed for details of past history of AIC and treatment
      emergent AIC. We identified 29/193 (15%) patients with history of AIC prior to
      ibrutinib start. Of 12 patients requiring AIC therapy at ibrutinib start, 8 (67%)
      were able to discontinue or de-escalate AIC treatment, and no patient had
      worsening of their AIC after initiating ibrutinib. Eleven (6%) patients developed
      treatment-emergent AIC after a median of 59 (range, 6-319) days following the
      initiation of ibrutinib, 7 of whom (64%) were able to continue ibrutinib. Overall
      and event-free survival from time of ibrutinib start were not significantly
      different between patients with history of AIC and those with no history of AIC.
      Treatment-emergent AIC were seen exclusively in patients with unmutated IGHV and
      were associated with a shorter EFS. These results suggest a low rate of treatment
      emergent AIC and improvement in patients with existing AIC.

PMID- 30117142
TI  - Excellent outcomes in children and adolescents with CNS+ burkitt lymphoma or
      other mature B-NHL using only intrathecal and systemic chemoimmunotherapy:
      results from FAB/LMB96 and COG ANHL01P1.

PMID- 30117143
TI  - How we treat the platelet glycoprotein defects; Glanzmann thrombasthenia and
      Bernard Soulier syndrome in children and adults.
AB  - The inherited platelet glycoprotein deficiencies, Glanzmann thrombasthenia (GT)
      and Bernard Soulier syndrome (BSS) are rare but important long-term bleeding
      disorders. Once diagnosed, affected patients should be referred to a specialist
      centre for bleeding disorders for general advice and ongoing management. Patients
      do not require prophylactic treatment and so the management of GT and BSS focuses
      around prophylactic treatment prior to high risk procedures and treatment in
      response to non-surgical bleeding events and, in women, the management of
      menorrhagia and pregnancy. There is no consistent approach to the treatment or
      prevention of bleeding complications. Management must be tailored for each
      individual and the approach may not be the same for different events, even for
      the same patient, depending on the type of accident or invasive procedure, the
      extent of bleeding and the presence or not of platelet refractoriness.

PMID- 30117145
TI  - Spontaneous regression of tumour in an elderly patient with squamous cell
      carcinoma of the cranial vertex pretreated with cetuximab monotherapy.

PMID- 30117144
TI  - Minimal residual disease status predicts outcome of acute myeloid leukaemia
      patients undergoing T-cell replete haploidentical transplantation. An analysis
      from the Acute Leukaemia Working Party (ALWP) of the European Society for Blood
      and Marrow Transplantation (EBMT).
AB  - Assessment of minimal residual disease (MRD) is being routinely used to assess
      response in patients with acute myeloid leukaemia (AML). While it is well
      established that pre-transplant positive MRD studies predict for relapse in
      patients transplanted either from matched sibling donors or matched unrelated
      donors, it is currently unknown whether MRD has comparable prognostic value in
      haploidentical stem cell transplantation (haplo-SCT). To this end we performed a
      retrospective analysis using the Acute Leukaemia Working Party/European Society
      of Blood and Marrow Transplantation multicentre registry. All adult AML patients
      with known MRD status at transplant who underwent a first T-cell replete haplo
      SCT while in remission between 2006 and 2016 were included. Two hundred and sixty
      five MRD-negative and 128 MRD-positive patients were assessed. In multivariate
      analysis, MRD-negative patients experienced lower relapse incidence and better
      leukaemia-free survival (LFS) compared to MRD-positive patients. Subset analysis
      for MRD-positive patients revealed that patients with donors positive for
      cytomegalovirus experienced decreased relapse rates as well as increased
      survival. A 6-month landmark analysis suggests that the clinical benefit of pre
      transplant MRD negativity in terms of relapse, overall survival and LFS is
      realized at this time point. Pre-transplant MRD status is potentially a pivotal
      prognosticator of outcome in AML patients undergoing T-cell replete haplo-SCT.

PMID- 30117146
TI  - Off-hour admission and impact on neurological outcome in endovascular treatment
      for acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: In the new era of endovascular treatment for acute
      ischemic stroke, one of the main predictors of good neurological outcome is a
      short time interval from stroke onset to recanalization of the occluded vessel.
      In this study, we examined the effect of on-hour vs off-hour admittance on the
      time intervals from stroke onset to recanalization in patients with acute
      ischemic stroke (AIS) undergoing endovascular treatment (EVT). METHODS: One
      hundred-ninety-eight patients receiving EVT for anterior AIS between 2007 and
      2016 were included. Time of day and weekday for stroke admittance were recorded
      as well as several time intervals. Age, sex, co-morbidities, admission National
      Institutes of Health Stroke Scale (NIHSS), intraprocedural blood pressure, blood
      glucose, modified Thrombolysis in Cerebral Ischemia score (mTICI) and
      neurological outcome at 3 months, measured as modified Rankin Scale (mRS), were
      registered. On-hour was defined as 8 am-4 pm weekdays, and off-hour as weekdays
      outside these hours and weekends. RESULTS: The time interval from CT (computed
      tomography) to recanalization was longer during off-hours, while no difference
      was seen in the time interval from stroke onset to CT. No statistically
      significant difference was seen in neurological outcome between the on- and off
      hour groups in a univariate analysis. CONCLUSIONS: Stroke admittance during off
      hours is associated with longer time interval from CT examination to vessel
      recanalization. The study highlights the need of logistic improvement and
      probably more resources off-hour in order to deliver an effective stroke care
      around the clock.

PMID- 30117147
TI  - Locally advanced skin cancers of the frail and elderly: consider adaptive split
      course radiotherapy.

PMID- 30117148
TI  - Safety Surveillance of Dietary Supplements: Importance, Challenges, and New
      Horizons.
AB  - Pharmacovigilance is defined as the science and activities relating to the
      detection, assessment, understanding, and prevention of adverse effects or any
      other possible drug-related problems.1 While current models of pharmacovigilance,
      with their tools and methodologies, were developed for prescription drugs, safety
      surveillance is just as important for over-the-counter health products such as
      dietary supplements. The practice of pharmacovigilance is challenging in itself;
      however, there are unique challenges associated with dietary supplements.2.

PMID- 30117149
TI  - Bendamustine and rituximab in elderly patients with low-tumour burden follicular
      lymphoma. Results of the LYSA phase II BRIEF study.
AB  - The treatment of low-tumour burden follicular lymphoma (LTBFL) remains a
      challenge. Rituximab-based strategies may be improved by adding chemotherapy.
      This Lymphoma Study Association multicentre phase II study assessed rituximab and
      bendamustine in 63 patients with untreated LTBFL who were aged over 60 years old
      and had a follicular lymphoma International Prognostic Index (FLIPI) score >=2.
      Induction comprised 4 weekly cycles of rituximab 375 mg/m2 intravenously combined
      with 2 cycles of bendamustine 90 mg/m2 days 1-2 with a 28-day interval, followed
      by twelve cycles of 375 mg/m2 rituximab maintenance therapy every 8 weeks. The
      primary endpoint was complete response (CR)/unconfirmed CR (CRu), at 12 weeks.
      Median age was 67.4 years and median FLIPI was 3. Ultimately, 18 patients (29%)
      had high tumour burden according to Groupe d'Etude des Lymphomes Folliculaires
      criteria. The 12-week CR/CRu rate was 54.0% and the overall response rate was
      93.7%. Surprisingly, 3 patients died during maintenance (2 sepsis, 1 neoplasm).
      Progression-free survival was 85.4% at 24 months. In LTBFL patients with FLIPI
      >=2, two cycles of rituximab and bendamustine result in a CR rate of 54.0%.
      However, the treatment-related deaths observed do not allow this regimen to be
      recommended for LTBFL patients aged over 60 years. EudraCT: 2010-020757-14;
      ClinicalTrials.gov: NCT01313611.

PMID- 30117150
TI  - Comparison of two prehospital predictive models for mortality and impaired
      consciousness after severe traumatic brain injury.
AB  - BACKGROUND: The primary aim was to investigate the performance of a National
      Advisory Committee for Aeronautics based predictive model (NACA-BM) for mortality
      at 14 days and a reference model using motor GCS (GCS-RM). The secondary aim was
      to compare the models for impaired consciousness of survivors at 14 days (IC-14;
      GCS <= 13). METHODS: Patients >=16 years having sustained TBI with an abbreviated
      injury scale score of head region (HAIS) of >3 were included. Multivariate
      logistic regression models were used to test models for death and IC-14. The
      discrimination was assessed using area under the receiver-operating curves
      (AUROCs); noninferiority margin was -5% between the AUROCs. Calibration was
      assessed using the Hosmer Lemeshow goodness-of-fit test. RESULTS: Six hundred and
      seventy seven patients were included. The median age was 54 (IQR 32-71). The
      mortality rate was 31.6%; 99 of 438 surviving patients (22.6%) had an IC-14.
      Discrimination of mortality was 0.835 (95%CI 0.803-0.867) for the NACA-BM and
      0.839 (0.807-0.872) for the GCS-RM; the difference of the discriminative ability
      was -0.4% (-2.3% to +1.7%). Calibration was appropriate for the NACA-BM (chi2
      8.42; P = 0. 393) and for the GCS-RM (chi2 3.90; P = 0. 866). Discrimination of
      IC-14 was 0.757 (0.706-0.808) for the NACA-BM and 0.784 (0.734-0.835) for the GCS
      RM; the difference of the discriminative ability was -2.5% (-7.8% to +2.6%).
      Calibration was appropriate for the NACA-BM (chi2 10.61; P = 0.225) and for the
      GCS-RM (chi2 6.26; P = 0.618). CONCLUSIONS: Prehospital prediction of mortality
      after TBI was good with both models, and the NACA-BM was not inferior to the GCS
      RM. Prediction of IC-14 was moderate in both models.

PMID- 30117152
TI  - Epstein-Barr virus load is higher in long-term Hodgkin lymphoma survivors
      compared to their unaffected twins and unrelated controls.

PMID- 30117151
TI  - Recurrent fungal infections in a Chinese patient with CARD9 deficiency and a
      review of 48 cases.
AB  - Deficiency of CARD9 (caspase recruitment domain-containing protein 9) has been
      reported in individuals with recurrent and invasive fungal infections. We report
      on a patient who first had Trichosporon asahii affecting the skin then Candida
      albicans infections involving the digestive tract and knee joint, along with
      elevated serum IgE. After stimulation with C. albicans, peripheral blood
      mononuclear cells of this patient produced less tumour necrosis factor-alpha,
      interferon-gamma and interleukin-17 than those of healthy controls. Furthermore,
      the serum IgE levels of this patient were positively correlated with the severity
      of fungal infection during the course of treatment. Sanger sequencing identified
      one homozygous frameshift mutation (p.D274fsX60) in CARD9. We further performed a
      review including 48 cases with CARD9 deficiency. According to the data published
      previously, CARD9-deficient patients demonstrated obviously elevated IgE in serum
      (median 1300 IU mL-1 ), which could distinguish them from otherwise healthy
      people with fungal infections (area under the curve 0.94, P < 0.001). Patients
      carrying the mutations Q289X and Q295X had a higher mortality rate (24% vs. 0%, P
      < 0.05). Patients with the mutations R18W, R35Q, R70W, G72S or Y91H in the CARD
      domain, and the nonsense mutation Q295X in the coiled-coil domain, seemed to be
      more prone to Candida infections (90% vs. 20%, P < 0.005) and central nervous
      system infections (60% vs. 12%, P < 0.005).

PMID- 30117153
TI  - The extent of pseudoxanthoma elasticum skin changes is related to cardiovascular
      complications and visual loss: a cross-sectional study.

PMID- 30117154
TI  - Associations between maternal socioeconomic position and psoriasis: a cohort
      study among the offspring of the Danish National Birth Cohort.
AB  - BACKGROUND: The socioeconomic determinants of paediatric-onset psoriasis have not
      been previously investigated. OBJECTIVE: To identify whether a social gradient
      exists for paediatric-onset psoriasis, using measures of maternal socioeconomic
      position. METHODS: Data on paediatric-onset psoriasis from 36 003 Danish National
      Birth Cohort offspring were cross-linked with nationwide registry data on
      maternal age and three measures of maternal socioeconomic position: maternal
      educational attainment, maternal labour market attachment and equivalized
      household income. Univariable and multivariable logistic regression analyses were
      conducted to estimate the odds ratios (ORs) of psoriasis in the offspring, in
      cohort analyses for data from the year of enrolment and cross-sectional analyses
      from the year of the 11-year follow-up. RESULTS: Maternal age at birth, maternal
      educational attainment and equivalized household income were inversely associated
      with psoriasis in the offspring. Low maternal educational attainment was
      associated with offspring psoriasis [adjusted OR 1.62, 95% confidence interval
      (CI) 1.20-2.18] after adjusting for maternal psoriasis and age in the cohort
      analysis. The crude OR of psoriasis in offspring of mothers in the highest
      quartile compared with mothers in the lowest quartile of equivalized household
      income was 0.57 (95% CI 0.43-0.76), and the adjusted OR was 0.59 (95% CI 0.44
      0.80) after adjusting for maternal psoriasis and age. Similar results were
      observed for data on maternal socioeconomic position at enrolment and at follow
      up. CONCLUSIONS: A steep social gradient in paediatric-onset psoriasis was
      observed. Maternal socioeconomic position may play a role in early-life exposure
      to modifiable risk factors for psoriasis. Future studies may help to elucidate
      which biological factors mediate the social gradient observed in our study.

PMID- 30117155
TI  - Assisted reproductive technology: an overview of Cochrane Reviews.
AB  - BACKGROUND: As many as one in six couples will encounter problems with fertility,
      defined as failure to achieve a clinical pregnancy after regular intercourse for
      12 months. Increasingly, couples are turning to assisted reproductive technology
      (ART) for help with conceiving and ultimately giving birth to a healthy live baby
      of their own. Fertility treatments are complex, and each ART cycle consists of
      several steps. If one of these steps is incorrectly applied, the stakes are high
      as conception may not occur. With this in mind, it is important that each step of
      the ART cycle is supported by good evidence from well-designed studies.
      OBJECTIVES: To summarise the evidence from Cochrane systematic reviews on
      procedures and treatment options available to couples with subfertility
      undergoing assisted reproductive technology (ART) procedures. METHODS: Published
      Cochrane systematic reviews of couples undergoing ART procedures (in vitro
      fertilisation or intracytoplasmic sperm injection) were eligible for inclusion in
      the overview. We also identified Cochrane reviews in preparation, for future
      inclusion.The primary outcome of the overview was live birth or the composite
      outcome live birth or ongoing pregnancy, as reported by the included reviews. Our
      secondary outcomes were clinical pregnancy, multiple pregnancy, miscarriage, and
      ovarian hyperstimulation syndrome. We excluded studies of intrauterine
      insemination and ovulation induction.We undertook selection of systematic
      reviews, data extraction, and quality assessment in duplicate. We assessed review
      quality by using the AMSTAR tool. We organised reviews by their relevance to
      specific stages in the ART cycle. We summarised their findings in the text and
      reported data for each outcome in 'Additional tables'. MAIN RESULTS: We included
      68 systematic reviews published in the Cochrane Library up to May 2018. All were
      of high quality. These reviews identified 38 interventions that were effective (n
      = 23) or promising (n = 15), and they identified 19 interventions that were
      ineffective (n = 2) or possibly ineffective (n = 17). For 15 interventions,
      review authors were unable to draw conclusions owing to lack of evidence.We
      identified an additional 11 protocols and four titles for future inclusion in
      this overview. AUTHORS' CONCLUSIONS: This overview provides the most up-to-date
      evidence on ART cycles from systematic reviews of randomised controlled trials.
      Fertility treatments are costly, and the stakes are high. Using the best
      available evidence to optimise outcomes is best practice. Evidence from this
      overview could be used to develop clinical practice guidelines and protocols that
      can be applied in daily clinical practice to improve live birth rates and reduce
      rates of multiple pregnancy, cycle cancellation, and ovarian hyperstimulation
      syndrome.

PMID- 30117156
TI  - Virtual reality simulation training for health professions trainees in
      gastrointestinal endoscopy.
AB  - BACKGROUND: Endoscopy has traditionally been taught with novices practicing on
      real patients under the supervision of experienced endoscopists. Recently, the
      growing awareness of the need for patient safety has brought simulation training
      to the forefront. Simulation training can provide trainees with the chance to
      practice their skills in a learner-centred, risk-free environment. It is
      important to ensure that skills gained through simulation positively transfer to
      the clinical environment. This updated review was performed to evaluate the
      effectiveness of virtual reality (VR) simulation training in gastrointestinal
      endoscopy. OBJECTIVES: To determine whether virtual reality simulation training
      can supplement and/or replace early conventional endoscopy training
      (apprenticeship model) in diagnostic oesophagogastroduodenoscopy, colonoscopy,
      and/or sigmoidoscopy for health professions trainees with limited or no prior
      endoscopic experience. SEARCH METHODS: We searched the following health
      professions, educational, and computer databases until 12 July 2017: the Cochrane
      Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase, Scopus, Web of
      Science, BIOSIS Previews, CINAHL, AMED, ERIC, Education Full Text, CBCA
      Education, ACM Digital Library, IEEE Xplore, Abstracts in New Technology and
      Engineering, Computer and Information Systems Abstracts, and ProQuest
      Dissertations and Theses Global. We also searched the grey literature until
      November 2017. SELECTION CRITERIA: We included randomised and quasi-randomised
      clinical trials comparing VR endoscopy simulation training versus any other
      method of endoscopy training with outcomes measured on humans in the clinical
      setting, including conventional patient-based training, training using another
      form of endoscopy simulation, or no training. We also included trials comparing
      two different methods of VR training. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed the eligibility and methodological quality of
      trials, and extracted data on the trial characteristics and outcomes. We pooled
      data for meta-analysis where participant groups were similar, studies assessed
      the same intervention and comparator, and had similar definitions of outcome
      measures. We calculated risk ratio for dichotomous outcomes with 95% confidence
      intervals (CI). We calculated mean difference (MD) and standardised mean
      difference (SMD) with 95% CI for continuous outcomes when studies reported the
      same or different outcome measures, respectively. We used GRADE to rate the
      quality of the evidence. MAIN RESULTS: We included 18 trials (421 participants;
      3817 endoscopic procedures). We judged three trials as at low risk of bias. Ten
      trials compared VR training with no training, five trials with conventional
      endoscopy training, one trial with another form of endoscopy simulation training,
      and two trials compared two different methods of VR training. Due to substantial
      clinical and methodological heterogeneity across our four comparisons, we did not
      perform a meta-analysis for several outcomes. We rated the quality of evidence as
      moderate, low, or very low due to risk of bias, imprecision, and
      heterogeneity.Virtual reality endoscopy simulation training versus no training:
      There was insufficient evidence to determine the effect on composite score of
      competency (MD 3.10, 95% CI -0.16 to 6.36; 1 trial, 24 procedures; low-quality
      evidence). Composite score of competency was based on 5-point Likert scales
      assessing seven domains: atraumatic technique, colonoscope advancement, use of
      instrument controls, flow of procedure, use of assistants, knowledge of specific
      procedure, and overall performance. Scoring range was from 7 to 35, a higher
      score representing a higher level of competence. Virtual reality training
      compared to no training likely provides participants with some benefit, as
      measured by independent procedure completion (RR 1.62, 95% CI 1.15 to 2.26; 6
      trials, 815 procedures; moderate-quality evidence). We evaluated overall rating
      of performance (MD 0.45, 95% CI 0.15 to 0.75; 1 trial, 18 procedures),
      visualisation of mucosa (MD 0.60, 95% CI 0.20 to 1.00; 1 trial, 55 procedures),
      performance time (MD -0.20 minutes, 95% CI -0.71 to 0.30; 2 trials, 29
      procedures), and patient discomfort (SMD -0.16, 95% CI -0.68 to 0.35; 2 trials,
      145 procedures), all with very low-quality evidence. No trials reported procedure
      related complications or critical flaws (e.g. bleeding, luminal perforation) (3
      trials, 550 procedures; moderate-quality evidence).Virtual reality endoscopy
      simulation training versus conventional patient-based training: One trial
      reported composite score of competency but did not provide sufficient data for
      quantitative analysis. Virtual reality training compared to conventional patient
      based training resulted in fewer independent procedure completions (RR 0.45, 95%
      CI 0.27 to 0.74; 2 trials, 174 procedures; low-quality evidence). We evaluated
      performance time (SMD 0.12, 95% CI -0.55 to 0.80; 2 trials, 34 procedures),
      overall rating of performance (MD -0.90, 95% CI -4.40 to 2.60; 1 trial, 16
      procedures), and visualisation of mucosa (MD 0.0, 95% CI -6.02 to 6.02; 1 trial,
      18 procedures), all with very low-quality evidence. Virtual reality training in
      combination with conventional training appears to be advantageous over VR
      training alone. No trials reported any procedure-related complications or
      critical flaws (3 trials, 72 procedures; very low-quality evidence).Virtual
      reality endoscopy simulation training versus another form of endoscopy
      simulation: Based on one study, there were no differences between groups with
      respect to composite score of competency, performance time, and visualisation of
      mucosa. Virtual reality training in combination with another form of endoscopy
      simulation training did not appear to confer any benefit compared to VR training
      alone.Two methods of virtual reality training: Based on one study, a structured
      VR simulation-based training curriculum compared to self regulated learning on a
      VR simulator appears to provide benefit with respect to a composite score
      evaluating competency. Based on another study, a progressive-learning curriculum
      that sequentially increases task difficulty provides benefit with respect to a
      composite score of competency over the structured VR training curriculum.
      AUTHORS' CONCLUSIONS: VR simulation-based training can be used to supplement
      early conventional endoscopy training for health professions trainees with
      limited or no prior endoscopic experience. However, we found insufficient
      evidence to advise for or against the use of VR simulation-based training as a
      replacement for early conventional endoscopy training. The quality of the current
      evidence was low due to inadequate randomisation, allocation concealment, and/or
      blinding of outcome assessment in several trials. Further trials are needed that
      are at low risk of bias, utilise outcome measures with strong evidence of
      validity and reliability, and examine the optimal nature and duration of
      training.

PMID- 30117157
TI  - Mosaic mutations in FGFR3 and FGFR2 are associated with naevoid acanthosis
      nigricans or RAVEN (round and velvety epidermal naevus).

PMID- 30117158
TI  - Traditional and commercial alcohols and esophageal cancer risk in Kenya.
AB  - Squamous cell esophageal cancer is common throughout East Africa, but its
      etiology is poorly understood. We investigated the contribution of alcohol
      consumption to esophageal cancer in Kenya, based on a hospital-based case-control
      study conducted from 08/2013 to 03/2018 in Eldoret, western Kenya. Cases had an
      endoscopy-confirmed esophageal tumor whose histology did not rule out squamous
      cell carcinoma. Age and gender frequency-matched controls were recruited from
      hospital visitors/patients without digestive diseases. Logistic regression was
      used to calculate odds ratios (ORs) and their 95% confidence intervals (CI)
      adjusting for tobacco (type, intensity) and 6 other potential confounders. A
      total of 422 cases (65% male, mean at diagnosis 60 (SD 14) years) and 414
      controls were included. ORs for ever-drinking were stronger in ever-tobacco users
      (9.0, 95% CI: 3.4, 23.8, with few tobacco users who were never drinkers) than in
      never-tobacco users (2.6, 95% CI: 1.6, 4.1). Risk increased linearly with number
      of drinks: OR for >6 compared to >0 to <=2 drinks/day were 5.2 (2.4, 11.4) in
      ever-tobacco users and 2.1 (0.7, 4.4) in never-tobacco users. Although most
      ethanol came from low ethanol alcohols (busaa or beer), for the same ethanol
      intake, if a greater proportion came from the moonshine chang'aa, it was
      associated with a specific additional risk. The population attributable fraction
      for >2 drinks per day was 48% overall and highest in male tobacco users. Alcohol
      consumption, particularly of busaa and chang'aa, contributes to half of the
      esophageal cancer burden in western Kenya.

PMID- 30117159
TI  - Risk of nutritional deficiencies for dogs on a weight loss plan.
AB  - OBJECTIVES: To determine how general practice veterinarians make weight loss
      recommendations for dogs and if nutrients become deficient when following these
      recommendations. MATERIALS AND METHODS: A questionnaire of general practice
      veterinarians was conducted to characterise weight loss recommendations made to
      clients. Using this data, progressive levels of caloric restriction were applied
      to top-selling commercial non-therapeutic adult maintenance diets and non
      therapeutic weight management diets. Nutrient intakes were compared to the
      National Research Council's Recommended Allowances for metabolic body weight
      using a theoretical current weight and ideal body weight for an obese dog.
      Nutrient intakes were also compared to recommendations from the Association of
      American Feed Control Officials using current body weight. RESULTS: Several
      nutrients were found at risk of deficiency, including choline, methionine,
      cysteine, selenium, eicosapentanoic acid, docosahexanoic acid, riboflavin,
      pantothenic acid and cobalamin in both non-therapeutic adult maintenance diets
      and non-therapeutic weight management diets. CLINICAL SIGNIFICANCE: Caution is
      warranted when making weight loss recommendations using commercial diets until
      further research on the nutrient needs of obese dogs undergoing weight loss is
      undertaken. Restriction of commercial diets to achieve weight loss in dogs may
      result in nutrient deficiencies.

PMID- 30117160
TI  - A rare case of choriocarcinoma after a positive pregnancy test in a
      postmenopausal woman.

PMID- 30117161
TI  - Bone cortical compactness in 'tree sloths' reflects convergent evolution.
AB  - Bone remodeling, one of the main processes that regulate bone microstructure,
      consists of bone resorption followed by the deposition of secondary bone at the
      same location. Remodeling intensity varies among taxa, but a characteristically
      compact cortex is ubiquitous in the long bones of mature terrestrial mammals. A
      previous analysis found that cortical bone in a few 'tree sloth' (Bradypus and
      Choloepus) specimens is heavily remodeled and characterized by numerous immature
      secondary osteons, suggesting that these animals were remodeling their bones at
      high rate until late in their ontogeny. This study aims at testing if this
      remodeling is generally present in 'tree sloths', using a quantitative analysis
      of the humeral cortical compactness (CC) among xenarthrans. The results of the
      investigation of humeral diaphyseal cross-sections of 26 specimens belonging to
      10 xenarthran species including specimens from both extinct and extant species
      indicate that in 'tree sloths' the CC is significantly lower than in the other
      sampled xenarthrans. No significant difference was found between the CC of the
      two genera of 'tree sloths'. Our results are consistent with the hypothesis that
      the cortical bone of 'tree sloths' in general undergoes intense and balanced
      remodeling that is maintained until late (possibly throughout) in their ontogeny.
      In the light of xenarthran phylogeny, low CC represents another convergence
      between the long-separated 'tree sloth' lineages. Although the exact structural
      and/or functional demands that are associated with this trait are hitherto
      unknown, several hypotheses are suggested here, including a relationship to their
      relatively low metabolism and to the mechanical demands imposed upon the bones by
      the suspensory posture and locomotion, which was independently acquired by the
      two genera of 'tree sloths'.

PMID- 30117162
TI  - Short-term outcomes of pulmonary embolism: A National Perspective.
AB  - BACKGROUND: Pulmonary embolism (PE) is associated with significant morbidity and
      mortality in hospitalized patients. Real time data on 90-day mortality, bleeding,
      and readmission is sparse. METHODS: The study cohort was derived from the
      National Readmission Data (NRD) 2013 to 2014. PE was identified using
      International Classification of Diseases, ninth Revision (ICD-9-CM) code
      415.11/3/9 in the primary diagnosis field. Any admission within 90 days of
      primary admission was considered a 90-day readmission. Readmission etiologies
      were identified by ICD-9 code in the primary diagnosis field. Co-primary outcomes
      were 90-day readmission and 90-day mortality. RESULTS: We identified 260 614
      patients with primary admission PE, 55 659 (21.36%) patients were readmitted
      within 90 days. Most of them were of old age (age >= 65 years: 49.04%) and
      females (52.78%). Among the etiologies of readmission pulmonary disorders
      (22.94%) (Including recurrent PE 7.33%), malignancies (8.31%), and bleeding
      disorders (6.75%) were the most important causes of 90-day readmissions. On
      multivariate analysis, higher readmission rates and 90 days mortality were seen
      in patients with heart failure, chronic pulmonary disease, Anemia, malignancy,
      and with higher Charlson score. Patients with longer length of stay during
      primary admission and who discharged to short/long-term facility were more likely
      get readmitted and die in 90 days. Paradoxically, obese patients showed an
      inverse relationship with co-primary outcomes. CONCLUSIONS: Older female patients
      were more likely to have a pulmonary embolism. High-risk groups such as heart
      failure, chronic pulmonary disease, anemia, and malignancy need to be given extra
      attention to prevent worse outcomes.

PMID- 30117163
TI  - Blood levels of cadmium and lead in relation to breast cancer risk in three
      prospective cohorts.
AB  - Cadmium and lead have been classified as carcinogens by the International Agency
      for Research on Cancer. However, their associations with breast cancer risk are
      unknown despite their persistence in the environment and ubiquitous human
      exposure. We examined associations of circulating levels of cadmium and lead with
      breast cancer risk in three case-control studies nested within the Cancer
      Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation
      into Cancer and Nutrition - Italy (EPIC-Italy) and the Northern Sweden Health and
      Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes
      from 1,435 cases and 1,433 controls using inductively coupled plasma-mass
      spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were
      calculated using random-effects models with each study result weighted by the
      within- and between-study variances. I2 values were calculated to estimate
      proportion of between study variation. Using common cut-points, cadmium levels
      were not associated with breast cancer risk in the CPS-II cohort (continuous RR =
      1.01, 95% CI 0.76-1.34), but were inversely associated with risk in the EPIC-
      Italy (continuous RR = 0.80, 95% CI 0.61-1.03) and NSHDS cohorts (continuous RR =
      0.73, 95% CI 0.54-0.97). The inverse association was also evident in the meta
      analysis (continuous RR = 0.84, 95% CI 0.69-1.01) with low between-study
      heterogeneity. Large differences in lead level distributions precluded a meta
      analysis of their association with breast cancer risk; no associations were found
      in the three studies. Adult cadmium and lead levels were not associated with
      higher risk of breast cancer in our large meta-analysis.

PMID- 30117165
TI  - Seroprevalence and risk factors for Toxocara infection among children in a rural
      community in Fars province, southern Iran.
AB  - The current study was performed to find out the seroprevalence of Toxocara
      infection in children living in a rural community in Fars province, southern
      Iran. Venous blood was taken from 617 children and evaluated for anti-Toxocara
      antibodies, using an ELISA system. Of the 617 studied children, 318 (51.5%) were
      boys and 299 (48.5%) were girls. Mean age of the participants was 9.2 (+/-10.7)
      years. Most cases of the recruited subjects (37.4%) were in the age group of 0-5
      years. Anti-Toxocara antibodies were detected in sera of 39 (6.3%) of children.
      From these, 23 (62.2%) were boys and 14 (37.8%) were girls. The infection rate
      was almost the same in different age groups. No statistically significant
      differences were seen between seropositivity to Toxocara infection and gender or
      age of the participants. Dogs or cats ownership was not associated with Toxocara
      seropositivity. The adjusted associations of the study variables suggested that
      the visceral leishmaniasis (VL) seropositivity is significantly associated with
      the seroprevalence of Toxocara infection (P < 0.001). Findings of the current
      study revealed that Toxocara infection is a common infection among children in
      the studied rural community in Iran. Preventive measurements are necessary to
      minimize the rate of Toxocara infection in children in such communities.

PMID- 30117164
TI  - Body mass index, calcium supplementation and risk of colorectal adenomas.
AB  - Calcium supplementation (1,200 mg/day) did not significantly reduce colorectal
      adenomas in our recent randomized, controlled trial (Vitamin D/Calcium Polyp
      Prevention Study, VCPPS, 2004-2013) in contrast to our previous trial (Calcium
      Polyp Prevention Study, CPPS, 1988-1996). To reconcile these findings, we
      identified participant characteristics that differed between the study
      populations and modified the effect of calcium supplementation on adenomas or
      high-risk findings (advanced or multiple adenomas). Compared to the CPPS, more
      participants in the VCPPS were obese (body mass index (BMI) >=30 kg/m2 ; 37.5%
      vs. 24.4%) and fewer had normal BMI (BMI <25 kg/m2 ; 18.5% vs. 31%). BMI appeared
      to modify the effect of calcium supplementation on adenomas and especially on
      high risk-findings: in the VCPPS, there was a 44% reduction in high-risk findings
      among individuals whose BMI was normal (RR = 0.56, 95% CI = 0.26-1.23), but not
      among overweight (RR = 1.09, 95% CI = 0.62-1.91) or obese (RR = 1.54, 95% CI =
      0.92-2.57) individuals (pinteraction = 0.03). Similarly, in the CPPS, there was a
      56% reduction in high-risk findings among individuals whose BMI was normal (RR =
      0.44, 95% CI = 0.26-0.74), but not among overweight (RR = 0.87, 95% CI = 0.55
      1.39) or obese (RR = 1.02, 95% CI = 0.57-1.82) individuals (pinteraction = 0.02).
      Standardization of each trial's findings to the BMI distribution in the other
      attenuated calcium's protective effect on adenomas in the CPPS but enhanced it in
      the VCPPS. In conclusion, 1,200 mg/day calcium supplementation may reduce risk of
      colorectal adenomas among those with normal BMI but not in overweight or obese
      individuals; and differences in BMI distribution partially account for the
      apparent difference in calcium efficacy between the two trials.

PMID- 30117166
TI  - Acidic mammalian chitinase tuning after enteric helminths eradication in
      inflammatory respiratory disease patients.
AB  - AIM: This study aimed at investigating the presence of intestinal parasitic
      infections in inflammatory respiratory diseases patients during the disease
      attack, and measuring the acidic mammalian chitinase (AMCase) gene expression in
      blood before and after infection eradication. METHODOLOGY: This case-control
      study included 123 inflammatory respiratory diseases patients and 120 apparently
      healthy individuals. Repeated stool examination was done, while total and
      specific IgE were measured. AMCase gene expression was analysed by real time
      polymerase chain reaction (RT-PCR). RESULTS: Infection was detected in 32.5% of
      the diseased and 23.25% of the healthy individuals. Higher rate of the helminthic
      infection was detected (23.57) in comparison to the protozoal (12.19%) in the
      patients. A significantly higher rate of infection with the chitin-rich helminths
      "Enterobius vermicularis & Hymenolepis nana" and level of anti-Dermatophagoide
      IgE were reported in the patients (14.63%, 6.5% and 23.57%, respectively). AMCase
      expression was significantly higher in helminths-infected patients than the
      noninfected, or protozoa infected. After infection eradication, AMCase expression
      significantly declined in the previously helminth-infected patients (mean +/- SD
      = 13.9 +/- 3.918 before and 4.515 +/- 1.93 after), but insignificantly affected
      in the protozoa infected (mean +/- SD = 2.095 +/- .285 before and 2.675 +/- 1.181
      after). CONCLUSION: Chitin-rich intestinal helminths are suspected to precipitate
      Th2-immune response in remote tissues by enhancing systemic AMCase expression
      through intestinal mucosa and macrophages irritation.

PMID- 30117167
TI  - The regulators of G protein signaling RGS16 and RGS18 inhibit protease-activated
      receptor 2/Gi/o signaling through distinct interactions with Galpha in live
      cells.
AB  - Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor (GPCR)
      activated by endogenous proteases, in particular, trypsin. Although regulators of
      G protein signaling (RGS) are known to inhibit GPCR/Galpha-mediated signaling,
      their specific effects on PAR2 are poorly understood at present. Here, we use a
      bioluminescence resonance energy transfer technique to investigate whether RGS16
      and RGS18 bind PAR2 in live cells to regulate PAR2/Galphai/o -mediated signaling.
      Notably, we find that RGS16 binds to PAR2 in the presence of Galphai while RGS18
      does not interact with PAR2, regardless of the presence of Galpha. Both RGS16 and
      RGS18 inhibit PAR2/Galphai/o -mediated signaling. To our knowledge, the current
      study is the first to highlight the effects of RGS proteins on PAR2-mediated
      signaling.

PMID- 30117168
TI  - A mini-STR typing system for degraded equine DNA.
AB  - Degraded biological samples are a challenge for testing laboratories. Genotyping
      success can be improved through the use of mini-STRs, by which primers are placed
      adjacent to the repeat motifs to reduce amplicon size. Here, we present a genetic
      profiling system comprising 13 autosomal and one X-linked dinucleotide-repeat
      markers and the SRY gene based on the internationally accepted equine parentage
      panel. The markers are divided into two panels with all alleles falling at or
      below 182 bp. The application of this method significantly increases the ability
      to profile difficult samples and to provide discriminating results to clients.

PMID- 30117170
TI  - Extranodal lymphomas in the public health system in Chile: Analysis of 1251
      patients from the National Adult Cancer Program.
AB  - The aim of the study was to describe the clinical and epidemiological
      characteristics, anatomic and histologic distribution, and treatment results of
      extranodal lymphomas (ENLs), diagnosed and treated in the public health system in
      Chile. We included patients with ENL diagnosed from 1998 to 2014, in 17 cancer
      centers, registered prospectively in the database of the National Adult Cancer
      Program (PANDA) of the Ministry of Health. Treatment was based on the local
      protocols for each lymphoma subtype. Extranodal lymphoma was documented in 1215
      of 4907 non-Hodgkin lymphomas diagnosed in that period (25%). Median age was 59
      years (range, 16-95), and 55% were female. The gastrointestinal (GI) tract was
      the most common location (38%), followed by the head and neck (24%) and the skin
      (15%). B-cell lymphomas accounted for 78% of cases, diffuse large B-cell lymphoma
      being the most common histologic subtype (68%). Mycosis fungoides/Sezary syndrome
      was the most frequent T-cell subtype (36%), followed by NK/T-cell lymphomanasal
      type (24%). In comparison with western countries, Chile showed a significantly
      high prevalence of NK/T-cell lymphoma nasal type, while the frequency of B-cell
      ENL and the anatomic distribution appeared similar, being GI the most commonly
      involved site.

PMID- 30117169
TI  - Outcome of allogeneic hematopoietic cell transplantation in patients with adult T
      cell leukemia.
AB  - Adult T-cell leukemia/lymphoma (ATL) is an aggressive peripheral T-cell neoplasm,
      and the outcome of patients with ATL after chemotherapy is poor. Allogeneic
      hematopoietic stem-cell transplantation (allo-HSCT) is a curative treatment
      modality for ATL, and four factors, namely, age > 50 years, male recipient, lack
      of complete remission at transplantation, and transplantation of cord blood, were
      previously shown to be associated with poor survival. We retrospectively analyzed
      the outcome of 21 patients with ATL who had undergone allo-HSCT at our hospital
      during a 3-year period. Of 21 patients, all had at least one of the above risk
      factors, and 18 had two or more. With a median follow-up of 19.7 months for
      living patients, the 1- and 2-year overall survival (OS) rates after
      transplantation were 34% and 27%, respectively. All relapse/progression events
      occurred within 1 year after allo-HSCT, and the cumulative incidence of
      relapse/progression at 1 year after allo-HSCT was 46.9%. The 100-day and 1-year
      nonrelapse mortality (NRM) rates were 19% and 42%, respectively. No significant
      difference in OS was observed between myeloablative and reduced-intensity
      conditioning regimens. The 3-year OS (27%) of ATL patients who received allo-HSCT
      and who had at least one adverse factor was somewhat poorer than the 3-year OS of
      33% identified in a nationwide study of allo-HSCT in ATL patients in Japan. The
      high relapse/progression and NRM rates are major problems to be solved to achieve
      better outcome.

PMID- 30117171
TI  - A prospective study to examine the association of the urinary and fecal
      microbiota with prostate cancer diagnosis after transrectal biopsy of the
      prostate using 16sRNA gene analysis.
AB  - INTRODUCTION: There is accumulating evidence that variations in the human
      microbiota may promote disease states including cancer. Our goal was to examine
      the association between urinary and fecal microbial profiles and the diagnosis of
      prostate cancer (PC) in patients undergoing transrectal biopsy of the prostate.
      MATERIALS AND METHODS: We extracted total DNA from urine and fecal samples
      collected before a prostate biopsy performed for elevated prostatic specific
      antigen in patients suspected of having PC. We then amplified the extracted DNA
      and sequenced it using bacterial 16S rRNA gene high-throughput next-generation
      sequencing platform, and analyzed microbial profiles for taxonomy comparing those
      patients diagnosed with PC with those who did not receive that diagnosis.
      RESULTS: We included 30 patients in our analysis (60 samples, one urine and one
      fecal per patient). The majority of patients with PC (10/14) had similar
      bacterial communities within their urinary sample profile and clustered
      separately than patients without cancer (n = 16). Differential analysis of the
      operational taxonomical units (OTUs) in urine samples revealed decreased
      abundance of several bacterial species in patients with prostate cancer. Analysis
      of the bacterial taxonomies of the fecal samples did not reveal any clustering in
      concordance with benign or malignant prostate biopsies. Patients who had a
      Gleason score (GS) of 6 (n = 11) were present in both urine bacterial community
      clusters, but patients with GS 7 or higher (n = 3) did not cluster tightly with
      non-cancer subjects. CONCLUSIONS: The urinary microbiota of patients with PC
      tends to cluster separately from those without this disease. Further research is
      needed to investigate the urinary microbiome potential of serving as a biomarker
      that could be used to improve the accuracy of pre-biopsy models predicting the
      presence of PC in post-biopsy tissue examination.

PMID- 30117172
TI  - Contrast-Enhanced Transrectal Ultrasound for Follow-up After Focal HIFU Ablation
      for Prostate Cancer.
AB  - The optimal strategy for imaging after focal therapy for prostate cancer is
      evolving. This series is an initial report on the use of contrast-enhanced
      transrectal ultrasound (TRUS) in follow-up of patients after high-intensity
      focused ultrasound (HIFU) hemiablation for prostate cancer. In 7 patients who
      underwent HIFU hemiablation, contrast-enhanced TRUS findings were as follows: (1)
      contrast-enhanced TRUS clearly showed the HIFU ablation defect as a sharply
      marginated nonenhancing zone in all patients; (2) contrast-enhanced TRUS
      identified suspicious foci of recurrent enhancement within the ablation zone in 2
      patients, facilitating image-guided prostate biopsy, which showed prostate
      cancer; and (3) contrast-enhanced TRUS findings correlated with multiparametric
      magnetic resonance imaging and biopsy histologic findings.

PMID- 30117173
TI  - Monoclonal gammopathy of undetermined significance in Chinese population: A
      prospective epidemiological study.
AB  - The aim of this study was to identify the prevalence of monoclonal gammopathy of
      undetermined significance (MGUS) in different groups of age and the clinical
      features in China. This multicenter prospective study enrolled 1797 health
      subjects. The overall prevalence of MGUS was 2.73%. The prevalence of different
      age groups was 1.19% (41-50 y), 1.16% (51-60 y), 2.19% (61-70 y), 3.66% (71-80
      y), and 7.76% (>=81 y). The prevalence of MGUS in male (n = 843) was 2.97%, while
      the prevalence of MGUS in female (n = 952) was 2.52%, but this difference of the
      two groups was not statistically significant. As for subtype of MGUS, IgG subtype
      was 55.1% (27 cases), IgA subtype was 14.3%, and IgM subtype was 12.2%. The M
      protein of one case became negative after 3 months, and the others remained
      positive without obvious disease transformation (follow-up duration: 3-7 mo).
      Thus, the prevalence of MGUS in China was similar to that in Mexican Americans,
      but lower than that in the other Asian country, American Whites, American Blacks,
      and Africans, and had a trend of increase with age. Male had higher prevalence of
      MGUS in China. The most common subtype was IgG.

PMID- 30117174
TI  - Genomic and clinical characterization of B/T mixed phenotype acute leukemia
      reveals recurrent features and T-ALL like mutations.
AB  - The B/T subtype of mixed phenotype acute leukemia (B/T MPAL) is defined by co
      expression of antigens of both B- and T-cell lineages on leukemic blasts.
      Although it has been suggested that multilineage antigen expression portends poor
      response to chemotherapy, the clinical characteristics and driver mutations that
      underlie the pathogenesis of this rare subtype of acute leukemia are scarcely
      known. We identified nine cases of B/T MPAL from multiple institutions and
      correlated clinical and immunophenotypic findings with next-generation sequencing
      data. We report that B/T MPAL commonly presents with lymphadenopathy in
      adolescence and young adulthood. While the tumors have diverse cytogenetic and
      genomic perturbations, recurrent acquired aberrations include mutations in the
      putative transcriptional regulator PHF6 and the JAK-STAT and Ras signaling
      pathways. Alterations were also identified in genes encoding hematopoietic
      transcription factors, cell cycle regulators/tumor suppressors, and chromatin
      modifying enzymes. The genomic landscape of B/T MPAL strongly resembles that of T
      ALL subgroups associated with early developmental arrest, while genetic
      alterations that are common in B-ALL were rarely seen. Two-thirds of the patients
      responded to ALL-based chemotherapy with or without stem cell transplantation.
      Our observations lay the groundwork for further study of the unique biology and
      clinical trajectory of B/T MPAL.

PMID- 30117175
TI  - Juvenile xanthogranuloma: A herald to the diagnosis of Erdheim-Chester disease in
      an adult with acute leukemia.
AB  - A 21-year-old man with B-cell acute lymphoblastic leukemia developed an eruption
      of multiple flesh-colored nodules and persistent fevers. A lesional biopsy showed
      diffuse dermal infiltrates of histiocytes, foam cells, and Touton giant cells
      consistent with juvenile xanthogranulomatosis. Upon further investigation, the
      patient's constellation of findings fit criteria for Erdheim-Chester disease.

PMID- 30117176
TI  - Optimal conditioning regimen for haplo-identical stem cell transplantation in
      adult patients with acquired severe aplastic anemia: Prospective de-escalation
      study of TBI and ATG dose.
AB  - This prospective study explored an optimal conditioning regimen to ensure
      engraftment with minimal toxicity in adult patients with severe aplastic anemia
      (SAA) who received haplo-identical stem cell transplantation from a related
      mismatched donor (Haplo-SCT). We explored a safe and sufficient dose of rabbit
      ATG (Thymoglobulin) in combination with 800 cGy total body irradiation (TBI) and
      fludarabine (Flu, 30 mg/m2 /day) for 5 days using step-by-step dose de
      escalation. The dose of ATG was de-escalated from 10 mg/kg (group 1), to 7.5
      mg/kg (group 2), to 5 mg/kg (group 3), and the TBI dose was reduced to 600 cGy
      (group 4) beginning in October 2014. If one patient developed transplant-related
      mortality (TRM) with engraftment in a group, we moved to the next lower dose
      group. Thirty-four patients were enrolled in groups 1-3 (n = 10) and 4 (n = 24).
      All patients achieved primary engraftment. The incidence of acute GVHD (grade >=
      2) and chronic GVHD (>= moderate) was 29.4% and 14.7%, respectively. With a
      median follow-up of 56.6 and 21.8 months in groups 1-3 and group 4, respectively,
      the 2-year probability of overall survival (91.7% in group 4 vs 70% in groups 1
      3, P = 0.155) and GVHD-free survival (78.4% in group 4 vs 50% in groups 1-3, P =
      0.115) was shown tended to be better in group 4. This study explored an optimal
      conditioning with step-by-step de-escalation dosage of ATG and TBI to reduce TRM
      with sustained graft function. TBI-600 cGy/Flu/intermediate-dose ATG resulted in
      feasible outcomes of Haplo-SCT for adult patients with SAA.

PMID- 30117177
TI  - Hemolysis and hemolysis-related complications in females vs. males with sickle
      cell disease.

PMID- 30117178
TI  - Diagnostic Performance of Ultrasound Elastography for Evaluating Portal
      Hypertension in Children: A Systematic Review and Meta-analysis.
AB  - OBJECTIVES: To assess the diagnostic performance of ultrasound (US) elastography
      in evaluating portal hypertension in children and compare the liver and spleen
      stiffness values between the portal hypertension and control groups. METHODS:
      Studies in the MEDLINE and Embase databases were selected that investigated the
      diagnostic performance of US elastography in children with portal hypertension up
      to December 21, 2017. Pooled sensitivity and specificity data were assessed by
      hierarchical logistic regression modeling. RESULTS: Eleven studies were included
      in the systematic review, and a meta-analysis could be conducted in 7 of these
      publications to evaluate the diagnostic performance of US elastography. The
      summary sensitivity and specificity of this method for liver stiffness were 90%
      (95% confidence interval [CI], 83%-94%) and 79% (95% CI, 73%-84%), respectively,
      and the area under the hierarchical summary receiver operating characteristic
      curve was 0.92 (95% CI, 0.90-0.94). A subgroup analysis of 5 transient
      elastographic studies revealed similar diagnostic performance (sensitivity, 90%;
      specificity, 78%). In 10 of the 11 studies that investigated liver stiffness and
      2 of the 3 studies that also measured spleen stiffness, patients in the portal
      hypertension group had a significantly higher stiffness value than the control
      group (P < .05). CONCLUSIONS: Ultrasound elastography shows good performance in
      diagnosing portal hypertension and can identify significant differences in liver
      and spleen stiffness in children with this condition. This method thus has
      considerable potential as a noninvasive tool for screening portal hypertension
      related complications in children with chronic liver disease.

PMID- 30117179
TI  - Small airways disease in an Operation Desert Storm Deployer: Case report and
      review of the literature on respiratory health and inhalational exposures from
      Gulf War I.
AB  - Constrictive Bronchiolitis (CB) has been reported in US Operation Iraqi
      Freedom/Enduring Freedom (OIF/OEF) deployers but not in those from prior US
      conflicts. A 62-year old presented with progressive dyspnea 13 years after
      deployment to the Persian Gulf in 1991-1992, where he was exposed to burning oil
      well fire emissions, dust storms, and other potential airborne hazards. In 2014,
      after a chest computed tomography (CT) scan demonstrated diffuse mosaic
      attenuation, he underwent surgical lung biopsy, which revealed CB. Deployers from
      both GWI and OIF/OEF share many exposures. As respiratory symptoms are a feature
      associated with Gulf War medically unexplained illness, there may be a role for
      renewed interest in evaluating GWI Veterans with unexplained respiratory symptoms
      for conditions such as CB, which may result from exposures relevant to deployers
      from both conflicts.

PMID- 30117180
TI  - Right atrial function by speckle tracking echocardiography in atrial septal
      defect: Prediction of atrial fibrillation.
AB  - BACKGROUND: Most antiarrhythmic interventional therapies for atrial fibrillation
      (AF) have been provided with special focus on the treatment of left-sided
      valvular disease and enlarged left atrium but few studies have assessed AF
      associated with congenital heart disease and dilated right atrium. HYPOTHESIS: We
      hypothesized that right atrial (RA) function assessed by two-dimensional (2DSTE)
      and three-dimensional (3DSTE) speckle-tracking echocardiography in patients with
      atrial septal defect (ASD) before and after percutaneous trancatheter closure
      could predict paroxysmal atrial fibrillation (PAF) development. METHODS: Seventy
      three patients with hemodynamically significant secundum ASD were prospectively
      studied and followed up for 6 months after occluder insertion and compared with a
      normal age-matched group (n = 73). A subgroup of 17 patients who developed PAF
      after device implantation was also studied. RA peak global longitudinal strain
      (PS) was determined using 2DSTE. Standard deviations (SDs) of times to peak
      strain (TPS) were calculated as indices of dyssynchrony. RA volumes, emptying
      fraction (EF), and expansion index (EI) were determined using 3DSTE. RESULTS: RA
      PS, EF, and EI (pre-closure values) were reduced in patients with atrial devices
      compared with controls, and further reductions were observed in patients with
      PAF. Pre-closure 3D-RA-EI (P = 0.009) and RA-TPS (P = 0.023) were independent
      predictors of PAF by multivariate analysis after adjustment for age and left
      atrial dysfunction. The areas under the ROC-curve (AUC) for 3D-RA-EI, RA-PS, RA
      TPS (pre-closure values) showed high discriminative values(from 0.76 to 0.85) in
      predicting PAF. By combining 3D-RA-EI and RA-TPS, the AUC increased to 0.90.
      CONCLUSIONS: Two-dimensional and three-dimensional speckle tracking
      echocardiography was clinically helpful in ASD patients in revealing right atrial
      dilatation and dysfunction pre-existent to device closure and associated with PAF
      development. RA parameters had a higher association with PAF compared to both the
      size of the implanted device and left atrial indices.

PMID- 30117181
TI  - Discordant HER2 immunohistochemical expression and gene amplification in ductal
      carcinoma in situ - evaluating HER2 in synchronous in-situ and invasive
      carcinoma.

PMID- 30117182
TI  - Sinonasal squamous cell carcinoma and EGFR mutations: a molecular footprint of a
      benign lesion.
AB  - AIMS: Molecular targeted therapy against EGFR kinase domain mutations has been
      successfully established for lung cancer. These mutations have now also been
      reported in head and neck tumours, particularly in inverted sinonasal papillomas
      (ISPs). The aim of this study was to clarify the spectrum of EGFR mutations in
      head and neck squamous cell carcinomas and papillomas. METHODS AND RESULTS: We
      examined EGFR mutations in 288 head and neck squamous cell carcinomas and 58 head
      and neck papillomas or polyps. EGFR mutations were detected in 24 (30%) of 80
      sinonasal squamous cell carcinomas (SNSCCs) and in 19 (90%) of 21 ISPs. Notably,
      15 (88%) of 17 SNSCCs that developed along with ISPs harboured EGFR mutations in
      both components, whereas EGFR mutations were detected in nine (14%) of 63 SNSCCs
      without any papilloma component. Analysis to detect other known driver oncogene
      mutations - KRAS, BRAF and HER2 - was also performed; none of these mutations was
      detected in SNSCCs. The other 208 non-sinonasal carcinomas and 37 non-ISP head
      and neck papillomas or polyps did not harbour EGFR mutations. CONCLUSIONS: Taken
      together with the specific involvement of EGFR mutations in ISP, a molecular
      benign lesion trail suggests that 26 (33%) of 80 SNSCCs developed in association
      with an ISP. SNSCCs with EGFR mutations may be biologically distinct among head
      and neck cancers.

PMID- 30117183
TI  - A note on pseudo-observations and left-truncation.
AB  - Pseudo-observations have been introduced as a way to perform regression analysis
      of a mean value parameter related to a right-censored time-to-event outcome, such
      as the survival probability or the restricted mean survival time. Since the
      introduction of the approach there have been several extensions from the original
      setting. However, the proper definition and performance of pseudo-observations
      under left-truncation has not yet been addressed. Here, we look at two types of
      pseudo-observations under right-censoring and left-truncation. We explored their
      performance in a simulation study and applied them to data on diabetes patients
      with left-truncation.

PMID- 30117184
TI  - Assessing inference of the basic reproduction number in an SIR model
      incorporating a growth-scaling parameter.
AB  - The standard mass action, which assumes that infectious disease transmission
      occurs in well-mixed populations, is popular for formulating compartmental
      epidemic models. Compartmental epidemic models often follow standard mass action
      for simplicity and to gain insight into transmission dynamics as it often
      performs well at reproducing disease dynamics in large populations. In this work,
      we formulate discrete time stochastic susceptible-infected-removed models with
      linear (standard) and nonlinear mass action structures to mimic varying mixing
      levels. Using simulations and real epidemic data, we demonstrate the sensitivity
      of the basic reproduction number to these mathematical structures of the force of
      infection. Our results suggest the need to consider nonlinear mass action in
      order to generate more accurate estimates of the basic reproduction number
      although its uncertainty increases due to the addition of one growth scaling
      parameter.

PMID- 30117185
TI  - P53 protein overexpression in de novo acute myeloid leukemia patients with normal
      diploid karyotype correlates with FLT3 internal tandem duplication and worse
      relapse-free survival.
AB  - Although ~50% of acute myeloid leukemia (AML) patients have a normal diploid
      karyotype by conventional cytogenetics at diagnosis, this patient subset has a
      variable disease course and outcome. Aberrant overexpression of the p53 protein
      is usually associated with TP53 alterations and a complex karyotype, but the
      prevalence and impact of p53 overexpression in AML with diploid cytogenetics is
      unknown. We examined 100 newly diagnosed AML patients to evaluate the impact of
      p53 expression status quantified in bone marrow core biopsy samples using
      immunohistochemistry and computer-assisted image analysis. A total of 24 patients
      had p53 overexpression defined as 3+ staining intensity in >=5% of cells; this
      finding correlated with lower platelet counts (P = .002), absence of CD34
      expression in blasts (P = .009), higher bone marrow blast counts (P = .04), and a
      higher frequency of FLT3 internal tandem duplication (P = .007). Overexpression
      of p53 independently predicted for shorter leukemia-free survival in patients who
      underwent allogeneic stem cell transplantation by univariate (P = .021) and
      multivariate analyses (P = .004). There was no correlation between MDM2 and p53
      protein expression in this cohort. We conclude that p53 expression evaluated by
      immunohistochemistry in bone marrow biopsy specimens at the time of AML diagnosis
      may indicate distinct clinical characteristics in patients with normal diploid
      cytogenetics and is a potentially valuable tool that can enhance risk
      stratification.

PMID- 30117186
TI  - High molecular weight hyaluronan protects cartilage from degradation by
      inhibiting aggrecanase expression.
AB  - Hyaluronan (HA) is an extracellular matrix (ECM) component of articular cartilage
      and has been used to treat patients with osteoarthritis (OA). A disintegrin and
      metalloproteinases with thrombospondin motifs (ADAMTSs) play an important role in
      cartilage degradation in OA. We have previously reported that ADAMTS4 and ADAMTS9
      were induced by cytokine stimulation. However, the effect of HA on the cytokine
      inducible ADAMTS9 has never been investigated. Moreover, it is unclear whether HA
      protects cartilage by suppressing aggrecan degradation. Here, we examined the
      effects of HA on ADAMTS expression in vitro and on cartilage degradation in vivo.
      ADAMTS9 expression was higher than that of the other aggrecanases (ADAMTS4 and 5)
      in human chondrocytes, chondrocytic cells, and rat cartilage. ADAMTS4 and 9 mRNA
      levels were upregulated in cytokine-stimulated chondrocytes and chondrocytic
      cells. Pre-incubation with HA significantly inhibited ADAMTS9 mRNA expression in
      cytokine-stimulated cells. In a rat OA model, Adamts5 and 9 mRNA levels were
      transiently increased after surgery; intra-articular HA injections attenuated the
      induction of Adamts5 and 9 mRNA. HA also blocked aggrecan cleavage by aggrecanase
      in OA rats in a molecular size-dependent manner. These results demonstrate that
      HA attenuates induced aggrecanases expression in OA and thereby protects
      articular cartilage degradation by this enzyme. Our findings provide insight into
      the molecular basis for the beneficial effects of HA in OA. (c) 2018 The Authors.
      Journal of Orthopaedic Research(r) Published by Wiley Periodicals, Inc. on behalf
      of Orthopaedic Research Society. J Orthop Res 9999:1-9, 2018.

PMID- 30117187
TI  - An assessment of applicability of existing approaches to predicting the
      bioaccumulation of conventional substances in nanomaterials.
AB  - The experimental determination of bioaccumulation is challenging, and a number of
      approaches have been developed for its prediction. It is important to assess the
      applicability of these predictive approaches to nanomaterials (NMs), which have
      been shown to bioaccumulate. The octanol/water partition coefficient (KOW ) may
      not be applicable to some NMs that are not found in either the octanol or water
      phases but rather are found at the interface. Thus the KOW values obtained for
      certain NMs are shown not to correlate well with the experimentally determined
      bioaccumulation. Implementation of quantitative structure-activity relationships
      (QSARs) for NMs is also challenging because the bioaccumulation of NMs depends on
      nano-specific properties such as shape, size, and surface area. Thus there is a
      need to develop new QSAR models based on these new nanodescriptors; current
      efforts appear to focus on digital processing of NM images as well as the
      conversion of surface chemistry parameters into adsorption indices. Water
      solubility can be used as a screening tool for the exclusion of NMs with short
      half-lives. Adaptation of fugacity/aquivalence models, which include
      physicochemical properties, may give some insights into the bioaccumulation
      potential of NMs, especially with the addition of a biota component. The use of
      kinetic models, including physiologically based pharmacokinetic models, appears
      to be the most suitable approach for predicting bioaccumulation of NMs.
      Furthermore, because bioaccumulation of NMs depends on a number of biotic and
      abiotic factors, it is important to take these factors into account when one is
      modeling bioaccumulation and interpreting bioaccumulation results. Environ
      Toxicol Chem 2018;37:2972-2988. (c) 2018 SETAC.

PMID- 30117188
TI  - Histological investigation of human glaucomatous eyes: Extracellular fibrotic
      changes and galectin 3 expression in the trabecular meshwork and optic nerve
      head.
AB  - Glaucoma is a leading cause of irreversible vision loss and is associated with
      fibrotic changes in two ocular tissues-the optic nerve head (ONH) and trabecular
      meshwork (TM). We investigated the differences in extracellular matrix components
      (ECM) including collagen, elastin, transforming growth factor beta-2, type-II
      receptor (TGFbetaRII) and Galectin3 (Gal3) in the glaucomatous human eyes to
      quantify fibrotic changes in ONH and TM. Glaucomatous and control human donor
      eyes were prepared for chemical and immunological staining to quantify ECM
      protein expression in the TM and ONH. Chemical staining included: Trichrome
      (collagen), Vernhoeff-Van Giesen (elastin) and Sirius Red (collagen).
      Immunohistochemistry was used to determine levels of Gal3 and TGFbeta2RII.
      Quantitative analyses were performed using Image J software. Student's t-test was
      used to compare groups and Pearson's test was used to determine correlations P
      values of 0.05 (or less) were considered statistically significant. Deposition of
      ECM proteins was elevated in glaucomatous tissues. There was increased collagen
      (P = 0.0469), Gal3 (P < 0.0001) and TGFbeta2RII (P = 0.0005) in the TM of
      glaucomatous eyes. Likewise, collagen (P = 0.0517) and Galectin3 (P = 0.041) were
      increased in the ONH glaucomatous eyes. There was a correlation of TGFbetaRII
      with Gal3 in the TM (P < 0.0001) and optic nerve (P = 0.0003). The TM and ONH of
      glaucomatous eyes showed increased expression of ECM proteins supporting a
      fibrotic pathology. Galectin3 and TGFbeta-2R II showed a positive correlation in
      TM and optic nerve supporting co-localization and suggesting their potential role
      in the glaucoma fibrotic process. Clin. Anat. 31:1031-1049, 2018. (c) 2018 The
      Authors. Clinical Anatomy published by Wiley Periodicals, Inc. on behalf of
      American Association of Clinical Anatomists.

PMID- 30117189
TI  - Local delivery of a zoledronate solution improves osseointegration of titanium
      implants in a rat distal femur model.
AB  - : This study aimed to determine whether locally applied anti-resorptive agents
      acetazolamide or zoledronic acid would improve mechanical stability in implant
      osseointegration when applied as a solution within the medullary canal. Thirty
      three rats received titanium-implants bilaterally in their intramedullary femoral
      canals. Prior to implantation, animals received 0.1 ml saline, 1 mM acetazolamide
      solution, or 0.7 mM zoledronic acid solution directly into the medullary cavity.
      The control group only received saline within the medullary canal while the
      treatment groups only received the respective treatment to which they were
      randomized. Animals were allowed to heal 4 weeks, at which time they were
      euthanized and femurs isolated for mechanical and radiographic evaluation. Push
      out force to failure increased 152% in the zoledronic acid group relative to the
      control. There was no significant difference in push-out force with acetazolamide
      relative to control. Also, zoledronic acid increased metaphyseal bone volume
      fraction 46% and increased metaphyseal bone-implant contact 58% relative to the
      control. Recent research exploring local injection of medications to improve
      implant osseointegration and minimize systemic-effects has failed to
      quantitatively evaluate implant fixation strength on non-hydroxyapatite coated
      implants or implants without previous bone compaction. This study demonstrated
      that a simple injection of zoledronic acid into the medullary canal, rather than
      coatings or commercial gels, can increase fixation strength of an uncoated
      titanium-implant. Our findings indicate simple injection of zoledronic acid in
      saline solution has the potential for improving fixation of uncemented joint
      implants. CLINICAL SIGNIFICANCE: Intramedullary injection of local bisphosphonate
      solutions could be implemented to improve osseointegration in cementless
      arthroplasty. (c) 2018 Orthopaedic Research Society. Published by Wiley
      Periodicals, Inc. J Orthop Res.

PMID- 30117190
TI  - A predictive model of suicidal ideation in Korean college students.
AB  - OBJECTIVE: The study was conducted to develop a theoretical model to
      comprehensively explain suicidal ideation in Korean college students by including
      resilience, belongingness, and college life adjustment in addition to depression
      and stress. DESIGN AND SAMPLE: This study was a descriptive survey with 291
      college students. MEASURES: Structural equation modeling was used to the
      hypotheses on this study. RESULTS: Belongingness and depression showed a
      statistically significant direct effect, and college life stress and
      belongingness showed a statistically significant indirect effect. Belongingness
      was the most influential, and all the predictors in combination had an
      explanatory power of 37% for suicidal ideation in college students. CONCLUSIONS:
      Findings suggest a model of suicidal ideation focused on perspective, protective
      factors; previous research provided a negative perspective with focus on risk
      factors for suicidal ideation. Findings can be used to develop diverse programs
      to decrease suicidal ideation in college students and help them to adjust to
      college life.

PMID- 30117191
TI  - Pig tracheal patchy xenotransplantation in the dog.
AB  - BACKGROUND: A long-segmental tracheal lesion is difficult to repair by tracheal
      allotransplantation due to the lack of a well-defined blood supply for blood
      vessel anastomosis. The donor trachea needs to be revascularized within a well
      vascularized soft tissue flap for several months to allow successful trachea
      allotransplantation. To date, xenotransplantation using the wild-type or
      genetically modified pig has been widely studied. The object of this study was to
      evaluate the feasibility of a small-sized (2 * 2 cm) wild-type pig tracheal
      patchy in a dog tracheal defect model before trying a long-segment tracheal
      defect model and using a genetically modified pig as a donor in dog
      xenotransplantation. METHOD: Three healthy beagle dogs (8-9 kg) were used as
      recipients, and one pig (20 kg) was used as the donor. A pig cartilaginous
      tracheal patchy (2 * 2 cm half tube) was sutured to the tracheal resected site in
      each dog. Antithymocyte globulin (2.5 mg/kg infusion, D0 and 1), tacrolimus (4.5
      mg/kg, twice a day for 2 months), and methylprednisolone sodium succinate (1
      mg/kg, IV, for 2 days and tapering) were administered for immunosuppression. The
      levels IL-2 and IFN-gamma in the serum were measured at D0, 7, and 28.
      Tracheoscopy was performed at D28, 60, and 90. The recipients were sacrificed at
      D90, and the expression of dog and pig genes in the graft was evaluated by PCR.
      Histopathological examination of the graft was conducted. RESULTS: All of the
      dogs survived without complications during the experimental period. Their IL-2
      and IFN-gamma levels were significantly increased at D7 after transplantation
      compared to D0 and D28 (P < 0.05). The pig tracheal patchy site was open, and no
      stenosis was observed until D90 on tracheoscopy, when pale mucosa erosion was
      observed; there was also remnant suture material at D28. However, the tracheal
      patchy sites gradually became similar to normal mucosa at D60 and 90. The
      expression of pig genes was detected in the graft by PCR. Normal epithelium and
      CD3 cells were observed in the histological examination at D90. CONCLUSION: In
      this study, our data suggest that the pig tracheal patchy can be successfully
      engrafted into the trachea of dog, although erosion of mucosa on the graft was
      seen at D30, in spite of the discordant species.

PMID- 30117192
TI  - Improved biomechanics of two alternative kyphoplasty cementation methods limit
      vertebral recollapse.
AB  - The clinical efficacy of vertebral cement augmentation for compression fractures
      (VCFs) remains undetermined. Recent studies have shown that refracture and
      progression of deformity may occur after augmentation with significant clinical
      consequences. Vertebral body height loss following kyphoplasty has also been
      observed with cyclic loading. We hypothesized that height loss is partly due to
      lack of cement fill past the margin of cancellous bone created by balloon
      expansion with subsequent failure under load. The biomechanical characteristics
      of two alternative cementation techniques were compared to standard kyphoplasty
      in cyclically loaded cadaveric VCF constructs. Sectioned osteoporotic
      thoracolumbar cadaveric spines were compressed to 75% of anterior vertebral
      height. Specimens were then allocated to standard kyphoplasty, balloon
      pressurization (BP), with reinflation of the balloon after 50% cement injection,
      or endplate post (EP), with perforation of the cavity rim using an articulating
      curette prior to injection. Following cementation, each specimen was
      preconditioned and loaded over 100,000 cycles. All techniques improved vertebral
      height (p's < 0.005). The EP and BP techniques provided greater cement fill than
      the standard technique (p's <= 0.01). Normalized vertebral height loss following
      100,000 cycles was reduced with the EP technique versus standard kyphoplasty (p <
      0.04). Height loss was inversely correlated with cement fill (p < 0.03). No
      vertebral recollapse occurred with the EP technique in blinded radiographic
      analysis. Statement of clinical significance: The EP technique demonstrated
      improved biomechanical characteristics versus the standard technique in cadaveric
      osteoporotic VCF constructs with decreased recollapse following cementation. This
      technique may have increased efficacy in cases when kyphoplasty more
      substantially improves vertebral body height. (c) 2018 Orthopaedic Research
      Society. Published by Wiley Periodicals, Inc. J Orthop Res.

PMID- 30117194
TI  - Firearm Ownership, Means Safety, and Suicidality.
AB  - OBJECTIVE: Means safety interventions are effective at reducing suicide rates.
      This study examined beliefs about firearm ownership or storage and suicide risk,
      lifetime suicidal thoughts, and openness to means safety. METHOD: A community
      sample of 107 American adult firearm owners (51.4% male; 82.2% White; m age =
      37.46) completed a series of self-report questionnaires via Amazon's Mechanical
      Turk. RESULTS: Hierarchical linear regressions indicated that beliefs regarding
      firearm ownership or storage were associated with openness to means safety
      measures to prevent a suicide attempt by someone else, but not to prevent one's
      own suicide attempt. Additionally, results from analyses of covariance indicated
      that firearm owners with lifetime ideation had stronger beliefs regarding the
      association between firearm ownership or storage and suicide risk. CONCLUSIONS:
      Findings indicate firearm owners' willingness to engage in means safety may be
      influenced by the degree to which they believe firearm storage is associated with
      suicide. Furthermore, firearm owners with prior suicide ideation are more open to
      the idea that firearm ownership and storage are related to suicide risk. Viewing
      suicide as salient to one's own life may serve as a focal point in efforts to
      increase openness to means safety among firearm owners.

PMID- 30117193
TI  - Microencapsulated adult porcine islets transplanted intraperitoneally in
      streptozotocin-diabetic non-human primates.
AB  - BACKGROUND: Xenogeneic donors would provide an unlimited source of islets for the
      treatment of type 1 diabetes (T1D). The goal of this study was to assess the
      function of microencapsulated adult porcine islets (APIs) transplanted ip in
      streptozotocin (STZ)-diabetic non-human primates (NHPs) given targeted
      immunosuppression. METHODS: APIs were encapsulated in: (a) single barium-gelled
      alginate capsules or (b) double alginate capsules with an inner, islet-containing
      compartment and a durable, biocompatible outer alginate layer. Immunosuppressed,
      streptozotocin-diabetic NHPs were transplanted ip with encapsulated APIs, and
      graft function was monitored by measuring blood glucose, %HbA1c, and porcine C
      peptide. At graft failure, explanted capsules were assessed for biocompatibility
      and durability plus islet viability and functionality. Host immune responses were
      evaluated by phenotyping peritoneal cell populations, quantitation of peritoneal
      cytokines and chemokines, and measurement of anti-porcine IgG and IgM plus anti
      Gal IgG. RESULTS: NHP recipients had reduced hyperglycemia, decreased exogenous
      insulin requirements, and lower percent hemoglobin A1c (%HbA1c) levels. Porcine C
      peptide was detected in plasma of all recipients, but these levels diminished
      with time. However, relatively high levels of porcine C-peptide were detected
      locally in the peritoneal graft site of some recipients at sacrifice. IV glucose
      tolerance tests demonstrated metabolic function, but the grafts eventually failed
      in all diabetic NHPs regardless of the type of encapsulation or the host
      immunosuppression regimen. Explanted microcapsules were intact, "clean," and free
      floating without evidence of fibrosis at graft failure, and some reversed
      diabetes when re-implanted ip in diabetic immunoincompetent mice. Histology of
      explanted capsules showed scant evidence of a host cellular response, and viable
      islets could be found. Flow cytometric analyses of peritoneal cells and
      peripheral blood showed similarly minimal evidence of a host immune response.
      Preformed anti-porcine IgG and IgM antibodies were present in recipient plasma,
      but these levels did not rise post-transplant. Peritoneal graft site cytokine or
      chemokine levels were equivalent to normal controls, with the exception of
      minimal elevation observed for IL-6 or IL-1beta, GRO-alpha, I-309, IP-10, and MCP
      1. However, we found central necrosis in many of the encapsulated islets after
      graft failure, and explanted islets expressed endogenous markers of hypoxia (HIF
      1alpha, osteopontin, and GLUT-1), suggesting a role for non-immunologic factors,
      likely hypoxia, in graft failure. CONCLUSIONS: With donor xenoislet
      microencapsulation and host immunosuppression, APIs corrected hyperglycemia after
      ip transplantation in STZ-diabetic NHPs in the short term. The islet xenografts
      lost efficacy gradually, but at graft failure, some viable islets remained,
      substantial porcine C-peptide was detected in the peritoneal graft site, and
      there was very little evidence of a host immune response. We postulate that
      chronic effects of non-immunologic factors, such as in vivo hypoxic and
      hyperglycemic conditions, damaged the encapsulated islet xenografts. To achieve
      long-term function, new approaches must be developed to prevent this damage, for
      example, by increasing the oxygen supply to microencapsulated islets in the ip
      space.

PMID- 30117195
TI  - The Type 1 diabetes 'honeymoon' period is five times longer in men who exercise:
      a case-control study.
AB  - Type 1 diabetes mellitus is an autoimmune disorder characterized by the
      destruction of insulin-secreting beta cells, and subsequent insulin deficiency.
      Shortly after diagnosis, 60% of adults with Type 1 diabetes experience a period
      of partial remission, or 'honeymoon' period, characterized by low insulin
      requirement and good glycaemic control [1]. Historically, the honeymoon period
      was defined as an insulin requirement of <= 0.5 units/kg/day together with HbA1c
      <= 58 mmol/mol (7.5%). Currently, the honeymoon period is defined as insulin dose
      adjusted A1c (IDAA1c ) <= 9, where IDAA1c = HbA1c (%) + [4* insulin dose
      (units/kg/day)] [2]. This shows good correlation with stimulated C-peptide, and
      therefore endogenous insulin secretion [2]. This article is protected by
      copyright. All rights reserved.

PMID- 30117196
TI  - When Diabetes Confronts HIV: Biological Sub-citizenship at a Public Hospital in
      Nairobi, Kenya.
AB  - This article investigates how international donor policies cultivate a form of
      biological sub-citizenship for those with diabetes in Kenya. We interviewed 100
      patients at a public hospital clinic in Nairobi, half with a diabetes diagnosis.
      We focus on three vignettes that illustrate how our study participants
      differentially perceived and experienced living with and seeking treatment and
      care for diabetes compared to other conditions, with a special focus on HIV. We
      argue that biological sub-citizenship, where those with HIV have consistent and
      comprehensive free medical care and those with diabetes must pay out-of-pocket
      for testing and treatment, impedes diabetes testing and treatment. Once
      diagnosed, many are then systematically excluded from the health care system due
      to their own inability to pay. We argue that the systematic exclusion from
      international donor money creates a form of biological sub-citizenship based on
      neoliberal economic policies that undermine other public health protections, such
      as universal primary health care.

PMID- 30117197
TI  - Henry Ware Cattell and Walt Whitman's Brain.
AB  - Henry Ware Cattell was a prominent pathologist and medical editor in late 19th
      and early 20th century America. Strangely, his name is unknown to most medical
      historians but is more widely known by aficionados of Walt Whitman's poetry. In
      1892, Cattell was involved in an incident that abruptly changed his life and
      decreased his commitment to pathology as a career. Cattell had been serving as
      the pathologist/prosector for the American Anthropometric Society at the time the
      poet Walt Whitman died. Cattell, the pathologist for the University of
      Pennsylvania's Wistar Institute, performed Whitman's autopsy on March 27, 1892;
      Whitman's brain was removed and was to join those of other prominent American
      intellectuals who had donated their brains to the Society's "Brain Club," but
      something went horribly wrong (allegedly, an assistant had dropped the brain and
      destroyed it) and Cattell kept this a secret. Full of self-doubt, Cattell was
      anguished about his inadequacies as a pathologist and was extremely worried about
      how all of this would affect his career when discovered. While still continuing
      to practice hospital-based pathology, he began to transition into an author and
      editor. This essay will provide a detailed biographical sketch of Henry Ware
      Cattell, address his sibling rivalry with his more famous brother James McKeen
      Cattell, briefly discuss the fad of 19th century intellectuals embracing the
      pseudo-science of phrenology and their participation in anatomical "brain clubs,"
      and, finally, address the mystery of what happened to Walt Whitman's brain. Clin.
      Anat. 31:988-996, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30117198
TI  - Retracing the observations and footsteps of Beauchene fils: A Blueprint for
      Scientific Research.
AB  - Throughout the years, scientific and personal research has led us on a historical
      journey to learn about the life of Beauchene fils (Edme Francois Chauvot de
      Beauchene), a French clinical anatomist, prosector, and surgeon responsible for
      introducing the disarticulated skull technique and the first citation of an
      intraneural cyst. This letter describes our research, travels, and conversations
      intended to uncover the fascinating history of Beauchene fils and his family and
      our journey full of unexpected twists and turns. During a trip to Paris, we
      learned of a possible inspiration for the disarticulated skull technique from
      skulls afflicted with la teigne (Tinea corporis, ring worm) at the Musee
      Dupuytren. We toured the estate of his family's summer home in Paron, France,
      where we discovered a portrait of Beauchene fils' father that had been
      misidentified in our recent publication. We also discovered the date of death and
      elusive burial site of Beauchene fils in Pere Lachaise cemetery in Paris. We hope
      to bring to light the life and contributions of a nearly unknown figure who
      influenced not only research on intraneural ganglion cysts and the articular
      theory, but also the future of the field of anatomy. Clin. Anat., 2018. (c) 2018
      Wiley Periodicals, Inc.

PMID- 30117199
TI  - microRNA-590-5p targets transforming growth factor beta1 to promote chondrocyte
      apoptosis and autophagy in response to mechanical pressure injury.
AB  - This study aimed to investigate the role of miR-590-5p in chondrocyte apoptosis
      and autophagy in response to mechanical pressure injury in vitro, as well as to
      elucidate its regulatory mechanism in the pathogenesis of osteoarthritis. We
      applied mechanical pressure of 10 MPa to chondrocytes for 60 minutes to establish
      the chondrocyte model of experimentally induced mechanical injury. We then
      investigated the expression of miR-590-5p in the injury model and the effects of
      miR-590-5p dysregulation on the expression of cell apoptosis-related and
      autophagy-related proteins. Cell apoptosis was detected by flow cytometry.
      Moreover, the potential targets of miR-590-5p were investigated. Mechanical
      pressure injury resulted in a significantly increased expression of miR-590-5p.
      Suppression of miR-590-5p significantly increased chondrocytes viability,
      inhibited chondrocytes apoptosis and autophagy in response to mechanical pressure
      injury. In addition, mechanical pressure injury led to a decreased expression of
      transforming growth factor beta1 (TGFbeta1). Moreover, TGFbeta1 was confirmed as
      a direct target of miR-590-5p. Knockdown of TGFbeta1 significantly induced
      chondrocytes apoptosis and autophagy in response to mechanical pressure injury,
      which was contrary to the effects of miR-590-5p suppression. Furthermore,
      overexpression of TGFbeta1 and miR-590-5p at the same time significantly reversed
      the effects of overexpression of miR-590-5p alone on chondrocytes apoptosis and
      autophagy. Our results indicate that upregulation of miR-590-5p may target
      TGFbeta1 to promote chondrocyte apoptosis and autophagy in response to mechanical
      pressure injury, thus contributing to the pathogenesis of osteoarthritis.

PMID- 30117200
TI  - Three-dimensional femoral head coverage in the standing position represents that
      measured in vivo during gait.
AB  - Individuals with over- or under-covered hips may develop hip osteoarthritis.
      Femoral head coverage is typically evaluated using radiographs, and/or computed
      tomography (CT) or magnetic resonance images obtained supine. Yet, these static
      assessments of coverage may not provide accurate information regarding the
      dynamic, three-dimensional (3-D) relationship between the femoral head and
      acetabulum. The objectives of this study were to: (1) quantify total and regional
      3-D femoral head coverage in a standing position and during gait, and (2)
      quantify the relationship between 3-D femoral head coverage in standing to that
      measured during gait. The kinematic position of the hip during standing and gait
      was measured in vivo for 11 asymptomatic morphologically normal subjects using
      dual fluoroscopy and model-based tracking of 3-D CT models. Percent coverage in
      the standing position and during gait was measured overall and on a regional
      basis (anterior, superior, posterior, inferior). Coverage in standing was
      correlated with that measured during gait. For total coverage, very little change
      in coverage occurred during gait (range: 35.0-36.7%; mean: 36.2%). Coverage at
      each time point of gait strongly correlated with coverage during standing (r =
      0.929-0.989). The regions thought to play an important role in weight bearing
      (i.e. anterior, superior, posterior) were significantly correlated with coverage
      in standing during the stance phase. Our results suggest that coverage measured
      in a standing position is a good surrogate for coverage measured during gait.
      Clin. Anat. 9999:1-7, 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30117201
TI  - Triboelectric Series of 2D Layered Materials.
AB  - Recently, as applications based on triboelectricity have expanded, understanding
      the triboelectric charging behavior of various materials has become essential.
      This study investigates the triboelectric charging behaviors of various 2D
      layered materials, including MoS2 , MoSe2 , WS2 , WSe2 , graphene, and graphene
      oxide in a triboelectric series using the concept of a triboelectric
      nanogenerator, and confirms the position of 2D materials in the triboelectric
      series. It is also demonstrated that the results are obviously related to the
      effective work functions. The charging polarity indicates the similar behavior
      regardless of the synthetic method and film thickness ranging from a few hundred
      nanometers (for chemically exfoliated and restacked films) to a few nanometers
      (for chemical vapor deposited films). Further, the triboelectric charging
      characteristics could be successfully modified via chemical doping. This study
      provides new insights to utilize 2D materials in triboelectric devices, allowing
      thin and flexible device fabrication.

PMID- 30117202
TI  - Fluorographene and Graphane as an Excellent Platform for Enzyme Biocatalysis.
AB  - The application of enzymes is a crucial issue for current biotechnological
      application in pharmaceutical, as well as food and cosmetic industry. Effective
      platforms for enzyme immobilization are necessary for their industrial use in
      various biosynthesis procedures. Such platforms must provide high yield of
      immobilization and retain high activity at various conditions for their large
      scale applications. Graphene derivatives such as hydrogenated graphene (graphane)
      and fluorographene can be applied for enzyme immobilization with close to 100 %
      yield that can result to activities of the composites significantly exceeding
      activity of free enzymes. The hydrophobic properties of graphene stoichiometric
      derivatives allowed for excellent non-covalent bonding of enzymes and their use
      in various organic solvents. The immobilized enzymes retain their high activities
      even at elevated temperatures. These findings show excellent application
      potential of enzyme biocatalysts immobilized on graphene stoichiometric
      derivatives.

PMID- 30117204
TI  - Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review.
AB  - In the last years, consumers are paying much more attention to natural medicines
      and principles, mainly due to the general sense that natural compounds are safe.
      On the other hand, there is a growing demand by industry for plants used in
      traditional medicine that could be incorporated in foods, nutraceuticals,
      cosmetics, or even pharmaceuticals. Glycyrrhiza glabra Linn. belongs to the
      Fabaceae family and has been recognized since ancient times for its
      ethnopharmacological values. This plant contains different phytocompounds, such
      as glycyrrhizin, 18beta-glycyrrhetinic acid, glabrin A and B, and isoflavones,
      that have demonstrated various pharmacological activities. Pharmacological
      experiments have demonstrated that different extracts and pure compounds from
      this species exhibit a broad range of biological properties, including
      antibacterial, anti-inflammatory, antiviral, antioxidant, and antidiabetic
      activities. A few toxicological studies have reported some concerns. This review
      addresses all those issues and focuses on the pharmacological activities reported
      for G. glabra. Therefore, an updated, critical, and extensive overview on the
      current knowledge of G. glabra composition and biological activities is provided
      here in order to explore its therapeutic potential and future challenges to be
      utilized for the formulation of new products that will contribute to human well
      being.

PMID- 30117203
TI  - Biomimetic Electronic Devices for Measuring Bacterial Membrane Disruption.
AB  - Antibiotic discovery has experienced a severe slowdown in terms of discovery of
      new candidates. In vitro screening methods using phospholipids to model the
      bacterial membrane provide a route to identify molecules that specifically
      disrupt bacterial membranes causing cell death. Thanks to the electrically
      insulating properties of the major component of the cell membrane, phospholipids,
      electronic devices are highly suitable transducers of membrane disruption. The
      organic electrochemical transistor (OECT) is a highly sensitive ion-to-electron
      converter. Here, the OECT is used as a transducer of the permeability of a lipid
      monolayer (ML) at a liquid:liquid interface, designed to read out changes in ion
      flux caused by compounds that interact with, and disrupt, lipid assembly. This
      concept is illustrated using the well-documented antibiotic Polymixin B and the
      highly sensitive quantitation of permeability of the lipid ML induced by two
      novel recently described antibacterial amine-based oligothioetheramides is shown,
      highlighting molecular scale differences in their disruption capabilities. It is
      anticipated that this platform has the potential to play a role in front-line
      antimicrobial compound design and characterization thanks to the compatibility of
      semiconductor microfabrication technology with high-throughput readouts.

PMID- 30117205
TI  - Suitability of existing commercial single nucleotide polymorphism chips for
      genomic studies in Bos indicus cattle breeds and their Bos taurus crosses.
AB  - Bos indicus cattle breeds are genetically distinct from Bos taurus breeds. We
      examined the performance of three SNP arrays, the Illumina BovineHD BeadChip
      (777k; Illumina Inc.), the Illumina BovineSNP50 BeadChip (50k) and the GeneSeek
      70k Indicus chip (75Ki; GeneSeek) in four B. indicus breeds (Gir, Kankrej,
      Sahiwal and Red Sindhi) and their B. taurus crosses, along with two B. taurus
      breeds, Holstein and Jersey. More SNPs on both Illumina SNP chips were
      monomorphic in B. indicus breeds (average 20.3%-29.3% on the 777k chip, 35.5%
      45.5% on the 50k chip) than in Holstein (19.7% on the 777k chip, 17.1% on the 50k
      chip). The proportion of monomorphic SNPs on the 75Ki chip was much lower, 4%
      (2.8%-7%) in B. indicus breeds, while it was 33.5% in Holstein. With on average
      164,357 heterozygous loci in B. indicus breeds, the 777k SNP chip has sufficient
      heterozygous loci to design a chip customized for B. indicus breeds. Principal
      component analysis clearly differentiated B. indicus from B. taurus breeds.
      Differentiation among B. indicus breeds was only achieved by plotting the third
      and fifth principal components using 777k genotype data. Admixture analysis
      showed that many B. indicus animals, previously believed to be of pure origin,
      are in fact had mixed ancestry. The extent of linkage disequilibrium showed
      comparatively higher effective population sizes in four B. indicus breeds
      compared to two B. taurus breeds. The results of admixture analyses show that it
      is important to assess the genomic composition of a bull before using it in a
      breeding programme.

PMID- 30117206
TI  - Hierarchical Self-Assembly of Supramolecular Coordination Polymers Using Giant
      Metal-Organic Nanocapsules as Building Blocks.
AB  - Controlling the self-assembly of giant molecular building blocks into complex
      architectures with similar hierarchy to biological species remains a major
      challenge in supramolecular chemistry. Akin to protein structure, here we present
      the self-assembly of giant molecular nanocapsules into supramolecular
      coordination polymers with controlled hierarchy from primary to secondary and
      tertiary structures. First, we successfully prepared discrete nanocapsules
      (secondary structures) consisting of multicomponents, such as organic macrocycles
      and metal-based secondary building units (primary structures). Second, these
      nanocapsules can self-organize into various 2D and 3D supramolecular coordination
      polymers (tertiary structures) through coordination-driven assembly. The
      periphery 24 flexible alkyl chains and 24 metal ions available for potential
      coordination make these nanocapsules comparable to functionalized solid
      nanoparticles with non-specific binding sites at the surface and allow the
      nanocapsules to self-adjust their orientations and coordination modes to
      facilitate the self-assembly process. This study sheds light on the self-assembly
      of giant building units with complex molecular structures and opens up
      possibilities for the design of new hierarchical architectures with innovative
      properties and functions in many applications such as biomimics, biomedicine, and
      molecular devices.

PMID- 30117207
TI  - Analysis of lanthionine ketimine ethyl ester in mouse serum, whole blood and
      tissues using ultrahigh-pressure liquid chromatography/tandem mass spectrometry.
AB  - RATIONALE: Preclinical studies in the search for treatments for several
      neurodegenerative diseases have identified lanthionine ketimine (LK) and its
      monoethyl ester derivative (LKE) as potential candidates. An ultrahigh-pressure
      liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) assay was developed
      to evaluate bioavailability by measuring these compounds in mouse serum, whole
      blood and brain tissue. METHODS: Following administration of LKE to mice for 3
      days in chow at 300 ppm, the animals were sacrificed, and LKE was extracted from
      serum, whole blood and brain tissues through protein precipitation using cold
      methanol. To enhance chromatographic separation and electrospray ionization, LK
      was methylated using diazomethane. Separations were carried out using C18
      reversed-phase UHPLC, and quantitative measurements were obtained using on-line
      triple-quadruple mass spectrometry with positive ion electrospray ionization,
      collision-induced dissociation and selected reaction monitoring. Tolbutamide was
      used as internal standard. RESULTS: LKE showed good recovery ranging from 77-90%
      in serum and 82-88% in brain tissue. An eight-point standard curve ranging from
      0.005 to 4.6 MUM was linear (R2 0.998). The average LKE detected in mouse serum
      was 277.42 nM, while the concentration in whole blood was 38 nM. Neither LK nor
      LKE was detected in brain tissues. CONCLUSIONS: A rapid quantitative method to
      measure LKE in mouse serum, whole blood and brain tissues using UHPLC/MS/MS was
      developed and validated following FDA guidelines. This method is suitable for
      bioavailability and pharmacokinetic studies.

PMID- 30117208
TI  - Simultaneous quantification of atropine and scopolamine in infusions of herbal
      tea and Solanaceae plant material by matrix-assisted laser desorption/ionization
      time-of-flight (tandem) mass spectrometry.
AB  - RATIONALE: Atropine (Atr) and scopolamine (Scp) are toxic secondary plant
      metabolites of species within the Solanaceae genus that can accidentally or
      intentionally reach the food store chain by inaccurate harvesting of any plant
      material, e.g. for herbal tea infusions. Ingestion may cause severe
      anticholinergic poisoning thus requiring risk-oriented determination in food and
      beverages. The suitability of matrix-assisted laser desorption/ionization time-of
      flight (tandem) mass spectrometry, MALDI-TOF MS(/MS), should be characterized for
      simultaneous analysis. METHODS: We herein present the first MALDI-TOF MS(/MS)
      procedure for quantitative determination of both alkaloids in herbal tea
      infusions and Solanaceae plant material. A standard additions procedure using
      triply deuterated Atr as internal standard was developed and validated. RESULTS:
      Tropane alkaloids were detected without interferences and the standard additions
      procedure allowed reliable quantification. Intraday and interday precision were
      less than 17% and corresponding accuracies were between 77% and 112%. Limits of
      detection in the spotting solution were found at 5 ng/mL (Atr) and 0.5 ng/mL
      (Scp). The assay was applied to diverse tea infusions as well as to berries and
      leaves of deadly nightshade and angel's trumpet. CONCLUSIONS: The usefulness of
      MALDI-TOF MS(/MS) for investigations of plant-derived samples to prove
      contaminations by small basic compounds was demonstrated. The elaborate procedure
      is reliable but quite laborious to obtain quantitative results, but MALDI-TOF
      MS(/MS) was also shown to be a valuable tool for rapid qualitative screening for
      Atr and Scp in plant extracts.

PMID- 30117209
TI  - BMAL1 deficiency promotes skeletal mandibular hypoplasia via OPG downregulation.
AB  - OBJECTIVES: Skeletal mandibular hypoplasia (SMH), a common type of developmental
      deformities, results in impaired aesthetics of facial profile, occlusal
      dysfunction and poor life quality. In this study, BMAL1 deficiency leads to SMH
      formation, and we aim to investigate the mechanism by which BMAL1 deficiency
      induces SMH. MATERIALS AND METHODS: Circadian rhythm-disordered mouse models were
      constructed by placing animals in a jet lag schedule of 6-h light advance every 7
      days for 4 or 8 weeks. The OPG expression was evaluated by histomorphometry,
      immunohistochemistry and western blot analysis. The mechanism by which BMAL1
      affects OPG expression was investigated by chromatin immunoprecipitation and
      luciferase reporter assays. The phenotypes caused by BMAL1 knockout can be
      rescued by exogenous supplementation with OPG. RESULTS: We demonstrate that the
      expressions of BMAL1 and OPG decreased in SMH patients. Circadian rhythm
      disordered mice and Bmal1-/- mice exhibited decreased expression of OPG, reduced
      bone mass and bone size of mandibles. Our results revealed that BMAL1 bound
      directly to the Opg promoter and upregulated its expression, thus inhibiting
      osteoclast differentiation. BMAL1 deficiency increased osteoclast differentiation
      by downregulating OPG expression. In vitro, the enhancement effect of osteoclast
      differentiation caused by BMAL1 knockdown was significantly reversed by exogenous
      supplementation with OPG. Importantly, bone loss caused by BMAL1 knockout can be
      partially reversed by injecting OPG Intraperitoneally. CONCLUSIONS: These results
      indicate that the circadian clock plays a critical role in the growth and
      development of mandible by regulating OPG expression, and present a potential
      therapeutic strategy to prevent SMH.

PMID- 30117210
TI  - Towards improving hospital workflows: An evaluation of resources to mobilize
      patients.
AB  - AIM: To characterize resources to safely mobilize different types of hospitalized
      patients. BACKGROUND: Current approaches to determine nurse-patient ratios do not
      always include information regarding the specific demands of patients who require
      extra resources to mobilize. Workflows must be designed with knowledge of
      resource requirements to integrate patient mobility into the daily nursing team
      care plan. METHODS: Nurse-led mobility sessions were evaluated on two adult
      hospital units, which consisted of nurse-patient encounters focused on patient
      mobility only. The resources assessed for each session were time-to-mobilize
      patient, time-to-document, need for additional staff support, and the need for
      assistive devices. Mobility sessions were also categorized by patient ambulation
      status, level of mobility limitations (low, medium and high) and diagnosis.
      RESULTS: In 212 total mobility sessions, the median time-to-mobilize and time-to
      document were 7.75 and 1.27 min, respectively. Additional staff support was
      required for 87% and 92% of patients with medium and high mobility limitations,
      respectively. All patients with low mobility limitations ambulated, and only 14%
      required additional staff. Ambulating patients with high mobility limitations was
      the most time-intensive (median 12.55 min). Ambulating stroke patients required
      one additional staff and an assistive device in 92% and 69% of the sessions,
      respectively. CONCLUSION: This study describes the resources associated with
      mobilizing inpatients with different levels of mobility impairments and
      diagnoses. IMPLICATIONS FOR NURSING MANAGEMENT: These results could assist
      nursing management with facilitating appropriate daily nurse-patient ratios and
      justify the need for assistive devices and staff support to safely mobilize
      patients.

PMID- 30117211
TI  - Functional divergence of a heterochromatin-binding protein during stickleback
      speciation.
AB  - Intragenomic conflict, the conflict of interest between different genomic regions
      within an individual, is proposed as a mechanism driving both the rapid evolution
      of heterochromatin-related proteins and the establishment of intrinsic genomic
      incompatibility between species. Although molecular studies of laboratory model
      organisms have demonstrated the link between heterochromatin evolution and hybrid
      abnormalities, we know little about their link in natural systems. Previously, we
      showed that F1 hybrids between the Japan Sea stickleback and the Pacific Ocean
      stickleback show hybrid male sterility and found a region responsible for hybrid
      male sterility on the X chromosome, but did not identify any candidate genes. In
      this study, we first screened for genes rapidly evolving under positive selection
      during the speciation of Japanese sticklebacks to find genes possibly involved in
      intragenomic conflict. We found that the region responsible for hybrid male
      sterility contains a rapidly evolving gene encoding a heterochromatin-binding
      protein TRIM24B. We conducted biochemical experiments and showed that the binding
      affinity of TRIM24B to a heterochromatin mark found at centromeres and
      transposons, histone H4 lysine 20 trimethylation (H4K20me3), is reduced in the
      Japan Sea stickleback. In addition, mRNA expression levels of Trim24b were
      different between the Japan Sea and the Pacific Ocean testes. Further expression
      analysis of genes possibly in the TRIM24B-regulated pathway showed that some
      gypsy retrotransposons are overexpressed in the F1 hybrid testes. We, therefore,
      demonstrate that a heterochromatin-binding protein can evolve rapidly under
      positive selection and functionally diverge during stickleback speciation.

PMID- 30117212
TI  - Cortical response to levodopa in Parkinson's disease patients with dyskinesias.
AB  - Levodopa-induced dyskinesias are a common and disabling side effect of
      dopaminergic therapy in Parkinson's disease, but their neural mechanisms in vivo
      are still poorly understood. Besides striatal pathology, the importance of
      cortical dysfunction has been increasingly recognized. The supplementary motor
      area in particular, may have a relevant role in dyskinesias onset given its
      involvement in endogenously generated actions. The aim of the present study was
      to investigate the levodopa-related cortical excitability changes along with the
      emergence of levodopa-induced peak-of-dose dyskinesias in subjects with
      Parkinson's disease. Thirteen patients without dyskinesias and ten with
      dyskinesias received 200/50 mg fast-acting oral levodopa/benserazide following
      overnight withdrawal (12 hr) from their dopaminergic medication. We targeted
      transcranial magnetic stimulation to the supplementary motor area, ipsilateral to
      the most dopamine-depleted striatum defined with single-photon emission computed
      tomography with [123 I]N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4
      iodophenyl)nortropane, and recorded transcranial magnetic stimulation-evoked
      potentials with high-density electroencephalography before and at 30, 60, and 180
      min after levodopa/benserazide intake. Clinical improvement from
      levodopa/benserazide paralleled the increase in cortical excitability in both
      groups. Subjects with dyskinesias showed higher fluctuation of cortical
      excitability in comparison to non-dyskinetic patients, possibly reflecting
      dyskinetic movements. Together with endogenous brain oscillation, levodopa
      related dynamics of brain state could influence the therapeutic response of
      neuromodulatory interventions.

PMID- 30117213
TI  - Modeling the pharmacokinetics and pharmacodynamics of sevoflurane using
      compartment models in children and adults.
AB  - BACKGROUND: Sevoflurane pharmacokinetics have been traditionally described using
      physiological models, while pharmacodynamics employed the use of minimal alveolar
      concentration. AIMS: The integrated pharmacokinetic-pharmacodynamic relationship
      of sevoflurane in both adults and children was reviewed using compartment models.
      We wished to delineate age-related changes in both pharmacokinetics and
      pharmacodynamics. METHODS: The bispectral index and sevoflurane endtidal
      concentration were continuously measured in 50 patients, aged 3-71 years,
      scheduled for minor surgery. During maintenance of anesthesia and after stable
      bispectral index values of 60-65 were obtained, the inspired concentration of
      sevoflurane was increased to 5 vol % for 5 minutes or until BIS 40 and then
      decreased. Data were analyzed using mammillary compartments with nonlinear mixed
      effects population modeling. The covariate effects of age and size were
      investigated. RESULTS: A three-compartment PK model adequately described
      sevoflurane pharmacokinetics. Size standardization using allometry explained
      clearance and volume changes with age. The equilibration half-time (1.48 minutes)
      increased with age, but could be predicted using allometry in those under 40
      years. The effect site concentration eliciting half the maximum response at age
      40 years was 1.3% (95%CI 1.22, 1.42) decreased with age from 1.6% at 3 years to
      1.1% at 70 years. CONCLUSION: Pharmacokinetic compartment models offer an
      alternative method to describe inhalation anesthetic drug disposition and
      effects.

PMID- 30117214
TI  - Traits of criticality in membrane potential fluctuations of pyramidal neurons in
      the CA1 region of rat hippocampus.
AB  - Evidence that neural circuits are operating near criticality has been provided at
      various levels of brain organisation with a presumed role in maximising
      information processing and multiscale activity association. Criticality has been
      linked to excitation at both the single-cell and network levels, as action
      potential generation marks an obvious phase transition from a resting to an
      excitable state. Using in vitro intracellular recordings, we examine irregular,
      small amplitude membrane potential fluctuations from CA1 pyramidal neurons of
      Wistar male rats. We show that these fluctuations, confounded with noise, carry
      information relevant to the neuronal state. The underlying dynamics exhibit
      intermittent characteristics shown to describe the temporal fluctuations of the
      order parameter of a macroscopic system at its critical point even in the absence
      of firing. An externally applied stimulus serves as the control parameter,
      driving the system in and out of its critical state. Based on our experimental
      observations we calculate the equivalent of the isothermal critical exponent
      deltah finding a value which depends on the applied stimulus. For each neuron
      there is a stimulus amplitude for which the critical behaviour becomes most
      pronounced. The corresponding mean value of deltah in the considered ensemble of
      neurons is deltah  ~ 1.89, close to theoretical predictions for critical
      networks. Finally, we show that the firing rate of a neuron decreases
      exponentially with deltah .

PMID- 30117215
TI  - Don't ask apple trees to give pears.

PMID- 30117216
TI  - Progress to publication of survey research presented at anesthesiology society
      meetings.
AB  - BACKGROUND: Understanding how survey methodology and quality measures are
      associated with progress from abstract presentation to manuscript publication can
      help optimize the design of survey research in anesthesiology, and enhance
      respondents' confidence in the value of survey participation. AIMS: The aim of
      this study was to determine if adherence to survey method recommendations and
      attainment of high response rates are associated with faster progress to
      publication among abstracts initially presented at anesthesiology society
      meetings. METHODS: Abstracts from the American Society of Anesthesiologists'
      (ASA) Annual Meeting, Association of Anaesthetists of Great Britain and Ireland
      (AAGBI) Annual Congress, and the International Anesthesia Research Society (IARS)
      Annual Meeting from 2011-2014 were reviewed. Abstracts reporting original survey
      data collection were included in a systematic search for resulting publications
      in peer-reviewed academic journals. Cox proportional hazards regression was used
      to analyze progress to publication. RESULT: Ninety-nine ASA, 76 AAGBI, and 30
      IARS abstracts met inclusion criteria. Among these abstracts, 43 (43%) from ASA,
      none from AAGBI, and 7 (23%) from IARS have been published as original research
      articles or brief reports. Surveying patients or caregivers, as opposed to
      medical professionals, was associated with increased likelihood of publication
      (hazard ratio [HR] = 4.4, 95% confidence interval [CI]: 1.6, 12.4, P = 0.005) as
      was a larger sample size (eg, >500 vs <100; HR = 12.9, 95% CI: 3.8, 43.6, P <
      0.001). CONCLUSIONS: While abstract presentation facilitates rapid dissemination
      of survey research findings, the impact and utility of such studies may be
      limited until a full manuscript is published. In our review, 25% of abstracts
      presenting survey data at major anesthesiology meetings were eventually
      published. Larger sample sizes and a target population of patients or caregivers
      increased the likelihood of survey research being published in full form.

PMID- 30117217
TI  - Losing my hand. Body ownership attenuation after virtual lesion of the primary
      motor cortex.
AB  - A fundamental component of the self-awareness is the sensation that we are acting
      with our own body. Thus, a coherent sense of self implies the existence of a
      tight link between the sense of body ownership and the motor system. Here, we
      investigated this issue by taking advantage of a well-known experimental
      manipulation of body ownership, i.e., the rubber hand illusion (RHI), during
      which the subjects perceive a fake hand as part of their own body. To test the
      effect of the motor system down-regulation on the RHI susceptibility, we designed
      a sham-controlled study, where the primary motor cortex (M1) excitability was
      modulated by off-line low-frequency repetitive transcranial magnetic stimulation
      (rTMS). After rTMS (real or sham), subjects underwent the RHI either on the right
      hand, contralateral to the inhibited hemisphere (Experiment 1), or on the left
      hand, ipsilateral to the inhibited hemisphere (Experiment 2). Only in Experiment
      1, the procedure strengthened the illusory experience, as proved by a significant
      increase, in rTMS compared to Sham, of both subjective (Embodiment/Disembodiment
      Questionnaires) and objective (Proprioceptive Drift) RHI measures. This evidence
      demonstrates that, when the M1 activity is down-regulated, the sense of body
      ownership is attenuated and the subjects become more prone to incorporate an
      alien body part. This, in turn, supports the existence of a mutual interaction
      between the sense of body ownership and the motor system, shedding new light on
      the construction of a coherent sense of self as an acting body.

PMID- 30117218
TI  - Determinants of attitudes and beliefs toward human papillomavirus infection,
      cervical cancer and human papillomavirus vaccine among parents of adolescent
      girls in Mysore, India.
AB  - AIM: This study examined the determinants of attitudes and beliefs about human
      papillomavirus (HPV) infection, cervical cancer and HPV vaccine among parents of
      adolescent girls in Mysore, India. METHODS: A random sample of 800 parents who
      had at least one adolescent-aged daughter attending school were recruited for a
      survey. RESULTS: Most parents (n = 778; 97.3%) completed the survey. Compared to
      Hindus, Muslims were more likely to perceive that their daughters are susceptible
      to HPV infection (adjusted odds ratio [aOR]: 4.94; 95% confidence interval [CI]:
      2.87, 8.49) or cervical cancer (aOR: 2.73; 95% CI: 1.55, 4.80). However, the
      likelihood of perceiving that daughters are susceptible to HPV infection (aOR:
      0.94; 95% CI: 0.90, 0.98) or cervical cancer (aOR: 0.95; 95% CI: 0.92, 0.99)
      decreased with an increase in the age of the parents. Perceived severity of HPV
      infection (aOR: 0.36; 95% CI: 0.14, 0.97) and cervical cancer (aOR: 0.33; 95% CI:
      0.15, 0.74) was lower among Muslims than Hindus. Muslims had lower odds of
      believing that HPV vaccine is safe (aOR: 0.47; 95% CI: 0.25, 0.89) or could
      protect against cervical cancer (aOR: 0.27; 95% CI: 0.16, 0.48), but were more
      likely to feel that HPV vaccination may cause girls to become more sexually
      active (aOR: 1.92; 95% CI: 1.09, 3.39). The odds of believing that HPV vaccine is
      effective increased with an increase in the age of the parents (aOR: 1.03; 95%
      CI: 1.003, 1.06). CONCLUSION: Among Indian parents, age and religion of parents
      are associated with parental attitudes and beliefs about the threat of HPV and
      cervical cancer as well as the risks and benefits of HPV vaccine.

PMID- 30117219
TI  - Clinical and echocardiographic risk factors for extubation failure in infants
      with congenital diaphragmatic hernia.
AB  - INTRODUCTION: Infants after surgical correction of congenital diaphragmatic
      hernia are at high risk for extubation failure, but little is known about
      contributing factors. Therefore, our study aimed to analyze clinical and
      echocardiographic parameters. MATERIALS AND METHODS: Data of 34 infants with
      congenital diaphragmatic hernia treated at our department (July 2013-December
      2015) were analyzed. Inclusion criteria were: presence of congenital
      diaphragmatic hernia and echocardiography performed within 48 hours before the
      first, and, in case of reintubation, the final extubation attempt. Infants were
      allocated to group A (extubation failure) and group B (extubation successful).
      RESULTS: Extubation failure occurred in 12/34 infants (35%). Infants in group A
      had a higher proportion of intrathoracic liver herniation (P = 0.001, OR 17
      [2.8/104.5]) and lower rates of the lung-to-head ratio (P = 0.042, 95% CI [
      0.4/20]), even as higher rates of extracorporeal membrane oxygenation (P = 0.001,
      95% CI [2.7/80.9]). The oxygenation index and the PaO2 /FiO2 ratio differed
      significantly between both groups (both P = 0.000; 95% CI [-11/-4.1] and
      [79/215], respectively). The mean airway pressure and fraction of inspired oxygen
      prior to extubation was significantly higher in group A (P = 0.008; 95% CI [-3.9/
      1.4]; P = 0.000; 95% CI [-0.6/-0.2], respectively). In addition, the respiratory
      severity score was higher in group A (P = 0.000; 95% CI [-7.3/-2.6]). In group A,
      administration of sildenafil and the vasoactive inotropic score were
      significantly higher (P = 0.037; OR 9 [0.9/88.6] and P = 0.013; 95% CI [-14/
      1.8], respectively). More infants in group A had need for a surgical patch repair
      of the diaphragm (P = 0.017; OR 7.2 [1.3/41.1]) and showed higher rates of
      relevant pleural effusions prior the extubation (P = 0.021; OR 6 [1.2/29.5]). The
      total duration of the ventilation and the length of hospital stay were longer in
      group A (P = 0.004; 95% CI [-915/-190] and P = 0.000; 95% CI [-110/-39],
      respectively). The prevalence of pulmonary hypertension was more frequent in
      group A (P = 0.012; OR 12 [1.3/114]), the time to peak velocity in the main
      pulmonary artery was significantly lower in group A (P = 0.024; 95% CI [2/25.6]),
      and these infants suffered more often from cardiac dysfunction (P = 0.007; OR 10
      [1.6/63.1]). CONCLUSION: Our results demonstrate that extubation failure in
      infants with a congenital diaphragmatic hernia is associated with several
      clinical and echocardiographic risk factors.

PMID- 30117220
TI  - Regular physical activity and insomnia: An international perspective.
AB  - Both very low and very high levels of regular physical activity have been
      associated with degraded sleep quality. Cross-national variations in habitual
      physical activity levels, therefore, may contribute to cross-national differences
      in insomnia prevalence. The present study assesses and compares the extent to
      which weekly durations of moderate-intensity physical activity contribute to
      insomnia risk. Demographic, sleep, physical activity and general health profiles
      were obtained from a convenience sample of 9,238 adults drawn from five countries
      (South Africa, Australia, China, South Korea and the UK) using social media.
      Insomnia prevalence, using DSM-5 criteria, ranged from 4.1% (China) to 14.8%
      (UK). Evaluating risk using logistic regression adjusted only for age and gender,
      the lowest level of activity (<10 continuous min per week) was associated with
      significant insomnia risk (odds ratio = 1.37; 95% confidence interval = 1.05
      1.79; p < 0.05). However, when adjusted for all covariates except country, only
      the highest level of physical activity (>300 min per week) was associated with
      significantly increased insomnia risk (odds ratio = 1.30; 95% confidence interval
      = 1.03-2.51; p < 0.05). Risk associated with high activity remained after the
      addition of "country" to the model (odds ratio = 1.31; 95% confidence interval =
      1.02-1.69; p < 0.05). Across all models, female gender, low-rated health, low
      education and older age consistently increased insomnia risk. These cross
      national data indicate that extremes of inactivity/activity can significantly
      influence insomnia risk independent of country. Insomnia risk associated with
      very low levels of activity may be mediated by poorer health and disadvantageous
      social status. However, while very high levels of activity increase insomnia risk
      independent of health and demographic factors, they may also confound with
      personally and occupationally demanding lifestyles.

PMID- 30117221
TI  - Use of infragluteal folds as a full-thickness skin graft donor site for
      construction of the neovagina in cases of Mullerian agenesis.
AB  - AIM: The aims of this study were to present the results of using infragluteal
      folds as a skin graft donor site in cases of Mullerian agenesis undergoing full
      thickness skin graft vaginoplasty and to evaluate the outcomes of the surgical
      technique. METHODS: Demographics and clinical parameters of 24 consecutive
      Mullerian agenesis patients refusing any dilatational procedure and undergoing
      neovaginal construction using infragluteal folds skin grafts from May 2004 to
      July 2015 were analyzed. RESULTS: The mean age of the patients was 21.5 +/- 5.7
      years. Five patients had nonfunctional rudimentary uterus, one patient had
      unilateral ovarian agenesis, one patient had unilateral renal agenesis, and one
      had undergone a previous vaginoplasty. There were no serious complications
      needing surgical or medical intervention. The depth of the neovagina in patients
      with a follow-up period of more than 6 months (n = 17) varied from 7 to 12 cm. Of
      these patients, the sexually active ones (n = 8) did not complain of dyspareunia
      or vaginal dryness during sexual intercourse. The resulting scars were
      satisfactory and acceptable for all patients. CONCLUSION: It has been our
      practice to use infragluteal folds as a skin graft donor site for full-thickness
      skin graft vaginoplasty. We believe that the results of this study demonstrate
      that this area is versatile and an excellent alternative to the groins and lower
      abdomen. Further clinical and histomorphological investigations are necessary for
      strong statements and results.

PMID- 30117222
TI  - Subcrestal Implant Placement and Recontouring Soft Tissue Using the Erbium YAG
      Laser to Manage Restorative Space in Implant Overdentures.
AB  - Subcrestal implant placement helps gain vertical restorative space at the
      location of the implants; however, this leads to the development of a tall
      mucosal cuff, necessitating the use of tall abutments. This article describes the
      technique of gaining restorative space by decreasing the height of the mucosal
      cuff with an Erbium YAG laser.

PMID- 30117223
TI  - Commentary on Amin et al. (2018): Cancer societies must do better on alcohol.

PMID- 30117224
TI  - Disordered eating in Jordanian adolescents.
AB  - BACKGROUND: Disordered eating attitudes and behaviours are linked to poor
      physical and psychological outcomes. AIM: To examine the individual,
      psychological, and socio-cultural factors associated with disordered eating
      attitudes among Jordanian adolescents. METHODS: A stratified sampling method was
      used to select school students aged 15 to 18 years from three governates in
      Jordan in 2013/2014. Participants filled out questionnaires on socio-demographic
      variables, the Eating Attitudes Test (EAT-26; to discriminate adolescents with
      disordered eating); the Body Shape Questionnaire (BSQ; used to measure
      psychological factors associated with disordered eating); Body Mass Index was
      calculated and obesity evaluated according to international cut off points (to
      categorize normal weight, overweight, and obese adolescents, and these categories
      were used as individual factors associated with disordered eating). RESULTS: A
      total of 963 (460 boys and 503 girls) participated in the study. Disordered
      eating (EAT score >= 20) was present in 389 (40.4%); body shape dissatisfaction
      (BSQ scores >=110) was present in 161 (16.8%). Overweight and obesity were found
      in 332 (34.5%) participants. Unhealthy weight loss behaviours (such as self
      induced vomiting, substance abuse, and smoking) were very common. Multivariate
      logistic regression analysis demonstrated that female sex, urban residence,
      distorted perceptions of weight, BMI (excess weight), body dissatisfaction, and
      socio-cultural variables (parents, peers and mass media) were significantly
      associated with disordered eating. CONCLUSION: Jordanian urban adolescents seem
      to embrace Western norms to fit in with the demands of Western culture. Socio
      cultural factors, particularly mass media, play a significant role in changing
      adolescents' norms. Prevention and intervention programs are needed to control
      these disorders.

PMID- 30117225
TI  - Depressive symptoms and actigraphy-measured circadian disruption predict head and
      neck cancer survival.
AB  - OBJECTIVE: Depressive symptoms have demonstrated prognostic significance among
      head and neck cancer patients. Depression is associated with circadian
      disruption, which is prognostic in multiple other cancer types. We hypothesized
      that depressive symptoms would be associated with circadian disruption in head
      and neck cancer, that each would be related to poorer 2-year overall survival,
      and that relationships would be mediated by tumor response to treatment. METHODS:
      Patients (N = 55) reported on cognitive/affective and somatic depressive symptoms
      (PHQ-9) and wore an actigraph for 6 days to continuously record rest and activity
      cycles prior to chemoradiation. Records review documented treatment response and
      2-year survival. Spearman correlations tested depressive symptoms and circadian
      disruption relationships. Cox proportional hazard models tested the predictive
      capability of depressive symptoms and circadian disruption, separately, on
      survival. RESULTS: Depressive symptoms were significantly associated with
      circadian disruption, and both were significantly associated with shorter
      survival (somatic: hazard ratio [HR] = 1.325, 95% confidence interval [CI] =
      1.089-1.611, P = .005; rest/activity rhythm: HR = 0.073, 95% CI = 0.009-0.563, P
      = .012; nighttime restfulness: HR = 0.910, 95% CI = 0.848-0.977, P = .009). Tumor
      response to treatment appeared to partly mediate the nighttime restfulness
      survival relationship. CONCLUSIONS: This study replicates and extends prior work
      with new evidence linking a subjective measure of depression and an objective
      measure of circadian disruption-2 known prognostic indicators-to shortened
      overall survival among head and neck cancer patients. Continued examination
      should elucidate mechanisms by which depressive symptomatology and circadian
      disruption translate to head and neck cancer progression and mortality.

PMID- 30117226
TI  - Anesthetic considerations for scoliosis surgery in a patient with recessive
      severe/lethal form of osteogenesis imperfecta.
AB  - Osteogenesis imperfecta is a heterogeneous genetic disorder characterized by bone
      fragility, with disease ranging from mild fractures to death in utero. We
      describe a child with autosomal recessive osteogenesis imperfecta type VIII
      (severe or lethal phenotype), who successfully underwent posterior spinal fusion,
      was extubated on postoperative day 1 and discharged home 25 days later. Recently
      identified recessive forms of osteogenesis imperfecta are associated with
      severe/lethal phenotype. Special consideration is needed in scoliosis surgery,
      with challenges arising from prone positioning, neurophysiology monitoring, and
      blood loss.

PMID- 30117227
TI  - Chronic oral rapamycin decreases adiposity, hepatic triglycerides and insulin
      resistance in male mice fed a diet high in sucrose and saturated fat.
AB  - NEW FINDINGS: What is the central question of this study? Whether chronic oral
      rapamycin promotes beneficial effects on glucose/lipid metabolism and energy
      balance when administered to mice with an obesogenic diet rich in saturated fat
      and sucrose has not been explored. What is the main finding and its importance?
      Chronic oral rapamycin reduces body weight and fat gain, improves insulin
      sensitivity and reduces hepatic steatosis when administered to mice with a high
      fat, high-sucrose diet. In addition, we make the new observation that there
      appear to be tissue-specific effects of rapamycin. Although rapamycin appears to
      impart its effects mainly on visceral adipose tissue, its effects on insulin
      sensitivity are mediated by subcutaneous adipose tissue. ABSTRACT: Excess
      adiposity is commonly associated with insulin resistance, which can increase the
      risk of cardiovascular disease. However, the exact molecular mechanisms by which
      obesity results in insulin resistance are yet to be understood clearly. The
      intracellular nutrient-sensing protein, mechanistic target of rapamycin (mTOR),
      is a crucial signalling component in the development of obesity-associated
      insulin resistance. Given that increased tissue activation of mTOR complex-1
      (mTORC1) occurs in obesity, diabetes and ageing, we hypothesized that
      pharmacological inhibition of mTORC1 would improve metabolic dysregulation in
      diet-induced obesity. We administered continuous rapamycin, a specific mTORC1
      inhibitor, orally to C57BL/6J mice concurrently with a high-fat, high-sucrose
      (HFHS) diet for 20 weeks. The control group received placebo microcapsules.
      Rapamycin-treated mice showed significantly reduced weight gain and adiposity
      (33.6 +/- 4.9 versus 40.4 +/- 3.0% body fat, P < 0.001, n = 8 mice per group),
      despite increased or equivalent food intake compared with the placebo group. The
      rapamycin-fed mice also demonstrated reduced plasma glucose (252 +/- 57 versus
      297 +/- 67 mg dl-1 , P < 0.001) and improved insulin sensitivity during insulin
      and glucose tolerance testing. Rapamycin-treated mice also had lower plasma
      triglycerides (48 +/- 13 versus 67 +/- 11 mg/dL, P < 0.01) and hepatic
      triglyceride content (89 +/- 15 versus 110 +/- 19 mg/g liver, P < 0.05) compared
      with the placebo group. A moderately low dose of rapamycin decreased adiposity
      and improved the metabolic profile in a model of diet-induced obesity. These data
      suggest that low-grade chronic mTORC1 inhibition might be a potential strategy
      for anti-obesity therapies.

PMID- 30117229
TI  - Acetaminophen, ibuprofen, and tramadol analgesic interactions after
      adenotonsillectomy.
AB  - BACKGROUND: The impact of tramadol in children given acetaminophen-ibuprofen
      combination therapy is uncertain in acute pediatric pain management. A model
      describing the interaction between these three drugs would be useful to
      understand the role of supplemental analgesic therapy. METHODS: Children
      undergoing tonsillectomy were given oral paracetamol and ibuprofen
      perioperatively. Blood was taken for paracetamol and ibuprofen drug assay on up
      to six occasions over 6 h after the initial dose. Tramadol was administered by
      caregivers for unacceptable postoperative pain. Pain was measured using the
      Parent's Postoperative Pain Measurement rating two hourly on the first
      postoperative day. A first-order absorption, one-compartment linear model with
      first-order elimination was used to describe acetaminophen and ibuprofen
      disposition. Analgesia was described using an EMAX model extended for three
      drugs, assuming additive effects. Curve fitting was performed using nonlinear
      mixed effects models. RESULTS: Pharmacodynamic parameter estimates, expressed
      using fractional Hill equation, were maximum effect (EMAX ) 0.65 (95%CI 0.54,
      0.74), the concentration of acetaminophen associated with 50% of the maximal drug
      effect (C50, ACET ) 7.06 (95%CI 7.03, 7.72) mg/L, and the ibuprofen C50 (C50, IBU
      ) 3.95 (95%CI 2.57, 7.53) mg/L. The Hill coefficient was 1.48 (95%CI 0.92, 2.62)
      and an interaction term was fixed at zero (additivity). The half-time (t1/2 keo)
      for equilibration between the plasma and effect site was 0.34 hour (95%CI 0.23,
      1.98) for acetaminophen and 1.04 hour (95%CI 0.75, 1.77) for ibuprofen. Tramadol
      had a C50, TRAM of 0.07 (95%CI 0.048, 1.07) mg/L with a t1/2 keo,TRAM 1.78 hour
      (95%CI 1.06, 1.96). CONCLUSION: Ibuprofen has an EC50 for analgesia in children
      similar to that of adults (3.95 mg/L; 95%CI 2.57-7.53, vs 5-10 mg/L adults). The
      maximum effect from combination therapy (ie, 65% reduction in pain score)
      achieves satisfactory analgesia with commonly used doses but increased dose adds
      little additional benefit. The addition of tramadol to this analgesic mixture
      prolongs analgesia duration.

PMID- 30117228
TI  - Anesthesia and the developing brain: A way forward for laboratory and clinical
      research.
AB  - All commonly used general anesthetics have been shown to cause neurotoxicity in
      animal models, including nonhuman primates. Opinion, however, remains divided
      over how cumulative evidence from preclinical and human studies in this field
      should be interpreted and its translation to current practices in pediatric
      anesthesia and surgery. A group of international experts in laboratory and
      clinical sciences recently convened in Genoa, Italy, to evaluate the current
      state of both laboratory and clinical research and discuss future directions for
      basic, translational, and clinical studies in this field. This paper describes
      those discussions and conclusions. A central goal identified was the importance
      of continuing to pursue laboratory research efforts to better understand the
      biological pathways underlying anesthesia neurotoxicity. The distinction between
      basic and translational experimental designs in this field was highlighted, and
      it was acknowledged that it will be important for future animal research to try
      to causally link structural changes with long-term cognitive abnormalities. While
      inherent limitations will continue to affect the ability of even large
      observational cohorts to determine if anesthesia impacts neurodevelopment or
      behavioral outcomes, the importance of conducting further large well-designed
      cohort studies was also emphasized. Adequately powered cohorts could clarify
      which populations are at increased risk, provide information on environmental and
      healthcare-related risk modifiers, and guide future interventional trials. If
      anesthetics cause structural or functional adverse neurological effects in young
      children, alternative or mitigating strategies need to be considered. While
      protective or mitigating strategies have been repeatedly studied in animals,
      there are currently no human data to support alternative anesthetic strategies in
      clinical practice. Lastly, it was noted that there is still considerable debate
      over the clinical relevance of anesthesia neurotoxicity, and the need to evaluate
      the impact of other aspects of perioperative care on neurodevelopment must also
      be considered.

PMID- 30117230
TI  - Improvement of medical judgments by numerical training in patients with multiple
      sclerosis.
AB  - BACKGROUND AND PURPOSE: People with multiple sclerosis (MS) have to face
      important decisions with regard to their medical treatment. The aim of this study
      was to evaluate whether a targeted cognitive training reduces framing effects and
      thus improves medical judgments. METHODS: This was a randomized, double-blind,
      cross-over study enrolling patients with relapsing-remitting MS and healthy
      controls (HCs). Participants were randomly assigned to training order A (first
      week, numerical training; second week, control training) or B (reverse order).
      The primary endpoint was changed in a framing task score (framing effect). In the
      framing task, participants evaluated the success of fictive medications on a 7
      point scale. Medications were described in either positive or negative terms.
      RESULTS: A total of 37 patients and 73 HCs performed either training order A (n =
      56) or B (n = 54). The framing effect decreased after the numerical training
      regardless of training order. No such decrease was found after the control
      training. Mean change in framing effect was -0.3 +/- 0.8 after the numerical
      training and 0.03 +/- 0.6 after the control training. This specific effect of
      training type was comparable between groups. CONCLUSION: Judgments of medical
      information improve in both patients with relapsing-remitting MS and HCs after a
      targeted numerical training. Thus, a specific cognitive intervention may help
      patients making informed decisions.

PMID- 30117231
TI  - Validating GO4KIDDS as a brief measure of adaptive skills in special education
      settings for children with severe intellectual disability.
AB  - BACKGROUND: Adaptive skills measures tend to be lengthy. The GO4KIDDS (Great
      Outcomes for Kids Impacted by Severe Developmental Disabilities; (Journal of
      Applied Research in Intellectual Disabilities, 58, 2015 and 594)) Brief Adaptive
      Behaviour Scale was developed to provide a brief assessment of adaptive skills.
      Our study aimed to examine the psychometric properties of G04KIDDS Brief Adaptive
      Scale in a large sample of children in special education. METHODS: Teachers
      reported on 361 students with severe to profound intellectual disability. The
      scale's factor structure was examined through principal components analysis
      (PCA), while its convergent validity was examined in relation to the Vineland
      (VABS-II; Vineland-II adaptive behavior scales, Circle Pines, MN, AGS and 2005).
      RESULTS: The PCA indicated a single component measuring overall adaptive skills,
      which had excellent internal consistency (alpha = 0.93), and convergent validity
      (Pearson's r = 0.81). CONCLUSIONS: Teacher-reported scores on GO4KIDDS Brief
      Behaviour Scale can provide a reliable and valid composite of adaptive skills in
      children with severe to profound intellectual disability. The scale will be
      useful to researchers and teachers who need a brief descriptive assessment of
      adaptive functioning.

PMID- 30117232
TI  - Effects of butyrate supplementation in antibiotic-free milk replacer and starter
      on growth performance in suckling calves.
AB  - The aim of this study was to evaluate butyrate supplementation of antibiotic-free
      milk replacer and starter on growth performance in male Holstein calves. Twenty
      nine calves were divided into two groups. Group C (n = 13) was fed antibiotic
      free milk replacer without supplementation, and Group B (n = 16) was fed
      antibiotic-free milk replacer supplemented with butyrate (1.6 % DM of Gustor
      BP70(r) ). Starter in Group B contained 0.3 % DM of Gustor BP70(r) . The intake
      of milk replacer was lower in group B than in C (p = 0.07 for the treatment x
      week interaction). Body weight (BW) and heart girth (HG) in group B was higher
      than in C during the experimental period (p = 0.07 and 0.01 for the treatment *
      week interaction, respectively). The duration of the weaning period in group B
      was shorter than in group C (p = 0.02). beta-hydroxybutyrate (BHBA) was higher in
      group B than in C (p = 0.04). Insulin like growth factor-1 (IGF-1) concentrations
      tended to be higher in group B than in C (p = 0.07 for treatment * week
      interaction). Our results show that butyrate supplementation in antibiotic-free
      milk replacer and starter exerted positive effects on growth performance in
      suckling calves.

PMID- 30117233
TI  - Relationship between reproductive medicine for women with severe complications
      and maternal death in Japan.
AB  - AIM: To investigate the influence of reproductive medicine in maternal death
      cases in Japan. METHODS: This retrospective study investigated the incidence of
      maternal deaths related to reproductive medicine in Japan from 2013 to 2015, and
      the relationship between fertility treatment and maternal death. RESULTS: Fifteen
      out of 134 women (11.2%) involved in this study who underwent treatment for
      infertility died. Four experienced pregnancy with severe maternal complications
      (26.6%). The complications were active systemic lupus erythematosus, exacerbated
      depression, uncontrolled arrhythmia and uncontrolled type 2 diabetes mellitus. At
      least three of these four died due to these complications. CONCLUSION: The
      maternal death rate of women who have undergone fertility treatment is similar to
      the birth rate due to assisted reproductive technology in Japan. Some maternal
      death cases involve severe uncontrolled complications. Therefore, medical
      histories should be evaluated before fertility treatment.

PMID- 30117234
TI  - 2D Organic Photonics: An Asymmetric Optical Waveguide in Self-Assembled Halogen
      Bonded Cocrystals.
AB  - Anisotropic organic molecular construction and packing are crucial for the
      optoelectronic properties of organic crystals. Two-dimensional (2D) organic
      crystals with regular morphology and good photon confinement are potentially
      suitable for a chip-scale planar photonics system. Herein, through the bottom-up
      process, 2D halogen-bonded DPEpe-F4 DIB cocrystals were fabricated that exhibit
      an asymmetric optical waveguide with the optical-loss coefficients of RBackward
      =0.0346 dB MUm-1 and RForward =0.0894 dB MUm-1 along the [010] crystal direction,
      which can be attributed to the unidirectional total internal reflection caused by
      the anisotropic molecular packing mode. Based on this crystal direction-oriented
      asymmetric photon transport, these as-prepared 2D cocrystals have been
      demonstrated as a microscale optical logic gate with multiple input/out channels,
      which will offer potential applications as the 2D optical component for the
      integrated organic photonics.

PMID- 30117235
TI  - Phagocytic and oxidative burst activity of phagocytic cells in peripheral blood
      and uterine washings in cows with clinical endometritis before and after
      intrauterine use of cephapirin and methisoprinol.
AB  - The aim of the study was to evaluate phagocytic and killing activity of
      phagocytic cells in blood and uterine flush of cows with endometritis before and
      after intrauterine (i.u.) administration of cephapirin and methisoprinol. The
      research was carried out on 28 cows with clinical endometritis. Animals were
      divided into four groups, each composed of seven cows, depending on the i.u.
      treatment used: Group A-cephapirin; Group B-methisoprinol; Group C-cephapirin and
      methisoprinol at the same time; and a control group-without medication. Using
      flow cytometry technique, the phagocytic activity of granulocytes and monocytes
      was identified, as well as the oxidative burst activity of neutrophils in the
      peripheral blood and uterine washings. Summarizing the results of the research,
      i.u. infusion of cephapirin caused a reduction in the phagocytic and killing
      activity of phagocytes. The i.u. use of methisoprinol increased phagocytic and
      killing activity of phagocytes in the uterus. Administering both listed
      substances simultaneously showed a decrease in phagocytosis, presumably due to
      the dominating inhibitor effect of the antibiotic. However, also an increase of
      mean fluorescence intensity was observed, presumably caused by the methisoprinol.
      Intrauterine use of immunostimulatory substances, can improve the effectiveness
      of the treatment of endometritis in cows.

PMID- 30117236
TI  - Microvascular invasion predicts a poor prognosis of solitary hepatocellular
      carcinoma up to 2 cm based on propensity score matching analysis.
AB  - AIM: Microvascular invasion (MVI) is not discussed for solitary hepatocellular
      carcinoma (HCC) up to 2 cm in the 8th Edition of the American Joint Committee on
      Cancer Staging Manual. The present study aimed to reappraise the influence of MVI
      on solitary HCC up to 2 cm in diameter. METHODS: Between January 2010 and
      December 2012, a retrospective cohort of 496 HCC patients from the Eastern
      Hepatobiliary Surgery Hospital was analyzed. Propensity score matching was
      carried out to balance the baseline characteristics. Survival analysis was
      carried out using the Kaplan-Meier method. Risk factors were evaluated using the
      Cox proportional hazards model. Multivariate logistic regression was used to
      identify the risk factors associated with MVI. RESULTS: All patients were
      classified into either an MVI-negative group (n = 332) or an MVI-positive group
      (n = 164). The MVI-positive group had poorer recurrence-free survival and overall
      survival before and after propensity score matching. The multivariate analysis
      showed that MVI; being male; increased total bilirubin levels, alanine
      transaminase levels and gamma-glutamyl transpeptidase levels; decreased albumin
      levels; and HBV DNA load >103  IU/mL were risk factors for recurrence-free
      survival. MVI, older age, lower albumin levels, and cirrhosis were risk factors
      for overall survival. Age <50 years, alpha-fetoprotein >20 ng/mL, and lack of or
      an incomplete capsule were significantly independent predictors for MVI.
      CONCLUSIONS: MVI had a negative impact on the prognosis of solitary HCC up to 2
      cm after curative hepatectomy. The 8th edition of the American Joint Committee on
      Cancer staging system could be improved by subdividing solitary HCC up to 2 cm
      according to MVI.

PMID- 30117237
TI  - Circulating orexin changes during withdrawal are associated with nicotine craving
      and risk for smoking relapse.
AB  - We examined the extent to which orexin measured during smoking and the early
      phase of abstinence was related to craving, withdrawal, stress hormones, and risk
      for smoking relapse in men and women. Considering its role in modulating nicotine
      related reward, we predicted that a reduction in circulating orexin during
      withdrawal would be associated with increased craving and risk for smoking
      relapse. Two hundred and eighty five participants provided biological samples and
      self-report information to identify predictors of smoking relapse. All
      participants attended two laboratory sessions, which were before and after a
      period of required abstinence from smoking. After quitting, participants also
      attended four weekly sessions to track smoking relapse. Only smokers who relapsed
      within the follow-up period exhibited reduced orexin levels during the initial
      withdrawal period; ACTH, but not craving nor cortisol, increased across the
      abstinence period for successful abstainers but not for relapsers. Sex
      differences in orexin and craving or withdrawal associations also emerged. Adding
      sex, HPA hormones, and self-reported measures of craving and withdrawal as
      potential mediators had minimal effects on the above abstinence and orexin
      effects. These results provide the first evidence that circulating orexin may be
      a useful marker of risk for relapse; and sex, adrenal hormones, and self-reported
      craving and withdrawal were not mediators of this effect. The results point to a
      promising pathway to investigate objective biological markers for craving and
      smoking relapse and highlight the complexity of the neurobiology of relapse.

PMID- 30117238
TI  - Effects of leuprorelin for the treatment of recurrent gynecological cancer by
      assessment including self-administered quality-of-life questionnaire.
AB  - AIM: To investigate the effects of leuprorelin using a self-administered quality
      of-life (QOL) questionnaire in patients with recurrent gynecological cancer.
      METHODS: Records of patients who received 3.75 mg leuprorelin every 4 weeks for
      the treatment of recurrent gynecological cancer were retrospectively reviewed.
      The physical domain of the QOL questionnaire, Care Notebook, was used to assess
      physical symptoms. Symptom deterioration was defined as a >=10-point increase in
      baseline score; otherwise, symptoms were defined as controlled. Radiological and
      serological responses were evaluated according to the 2011 Gynecological Cancer
      Intergroup criteria. RESULTS: From 2007 to 2015, 25 patients were administered
      leuprorelin for the treatment of epithelial ovarian cancer, granulosa cell tumor,
      endometrial cancer, endometrial stromal sarcoma and clear cell cervical cancer
      (in 13, 3, 6, 2 and 1 patients, respectively). Twenty patients had received a
      median of three lines (range 1-12 lines) of chemotherapy. Ten patients had
      progressive disease during their previous round of chemotherapy. Twenty patients
      completed the questionnaire every 4 weeks. Following leuprorelin treatment for 8
      weeks, the symptom and disease control rates were 65% (13/20) and 44% (11/25),
      respectively. Two patients, one each with granulosa cell tumor and endometrial
      cancer, had stable disease at 6 months. Among the 20 patients who completed the
      QOL questionnaire, symptom control and disease control at 8 weeks showed a
      significant correlation (P = 0.016). CONCLUSION: Leuprorelin had minimal
      anticancer activity. The physical domain of the QOL questionnaire could be used
      to assess effects of hormonal treatment.

PMID- 30117239
TI  - Ryoji Noyori ACES Award: M. G. Banwell / Liebig Memorial Medal: W. Schnick /
      Izatt-Christensen Award: P. A. Gale / Cram Lehn Pedersen Prize: R. Klajn.

PMID- 30117240
TI  - Discovery of a neuroendocrine tumor of the caecum by mammary metastasis using 18F
      DOPA-PET.
AB  - Neuroendocrine tumors (NET) develop from the diffuse endocrine system. These are
      rare tumors that can affect diverse organs. We present here the case of a 42-year
      old female patient in whom a NET of the breast was discovered that was likely not
      of mammary origin. The main challenge was finding the primary tumor using
      immunohistochemistry and specific medical imaging modalities for NET. The primary
      tumor was localized at the last ileal loop upstream of the Bauhin valve thanks to
      the use of 18F-DOPA-PET. Ileocaecal resection by laparoscopy was performed. A WHO
      grade 2 NET of the ileum measuring 2.2 cm * 1.5 cm was found that infiltrated the
      submucosa with six metastatic lymph nodes of the eight removed (6N+/8). This
      unusual clinical case is the first one of a digestive NET of the ileum-caecal
      junction by mammary metastasis.

PMID- 30117242
TI  - Laparoscopic treatment for an inguinal Richter's hernia: an unusual indication in
      case of acute small bowel obstruction.

PMID- 30117241
TI  - Teachers' influence on purchase and wear of children's glasses in rural China:
      The PRICE study.
AB  - IMPORTANCE: Uncorrected refractive error causes 90% of poor vision among Chinese
      children. BACKGROUND: Little is known about teachers' influence on children's
      glasses wear. DESIGN: Cohort study. PARTICIPANTS: Children at 138 randomly
      selected primary schools in Guangdong and Yunnan provinces, China, with
      uncorrected visual acuity (VA) <=6/12 in either eye correctable to >6/12 in both
      eyes, and their teachers. METHODS: Teachers and children underwent VA testing and
      completed questionnaires about spectacles use and attitudes towards children's
      vision. MAIN OUTCOME MEASURES: Children's acceptance of free glasses, spectacle
      purchase and wear. RESULTS: A total of 882 children (mean age 10.6 years, 45.5%
      boys) and 276 teachers (mean age 37.9 years, 67.8% female) participated. Among
      teachers, 20.4% (56/275) believed glasses worsened children's vision, 68.4%
      (188/275) felt eye exercises prevented myopia, 55.0% (151/275) thought children
      with modest myopia should not wear glasses and 93.1% (256/275) encouraged
      children to obtain glasses. Teacher factors associated with children's glasses
      related behaviour included believing glasses harm children's vision (decreased
      purchase, univariate model: relative risk [RR] 0.65, 95% CI 0.43, 0.98, P <
      0.05); supporting children's classroom glasses wear (increased glasses wear,
      univariate model: RR 2.20, 95% CI 1.23, 3.95, P < 0.01); and advising children to
      obtain glasses (increased free glasses acceptance, multivariate model: RR 2.74,
      95% CI 1.29, 5.84, P < 0.01; increased wear, univariate model: RR 2.93, 95% CI
      1.45, 5.90, P < 0.01), but not teacher's ownership/wear of glasses. CONCLUSIONS
      AND RELEVANCE: Though teachers had limited knowledge about children's vision,
      they influenced children's glasses acceptance.

PMID- 30117243
TI  - Transcriptomic and proteomic responses of the oceanic diatom Pseudo-nitzschia
      granii to iron limitation.
AB  - Diatoms are a highly successful group of photosynthetic protists that often
      thrive under adverse environmental conditions. Members of the genus Pseudo
      nitzschia are ecologically important diatoms which are able to subsist during
      periods of chronic iron limitation and form dense blooms following iron
      fertilization events. The cellular strategies within diatoms that orchestrate
      these physiological responses to variable iron concentrations remain largely
      uncharacterized. Using a combined transcriptomic and proteomic approach, we
      explore the exceptional ability of a diatom isolated from the iron-limited
      Northeast Pacific Ocean to reorganize its intracellular processes as a function
      of iron. We compared the molecular responses of Pseudo-nitzschia granii observed
      under iron-replete and iron-limited growth conditions to those of other model
      diatoms. Iron-coordinated molecular responses demonstrated some agreement between
      gene expression and protein abundance, including iron-starvation-induced
      proteins, a putative iron transport system and components of photosynthesis and
      the Calvin cycle. Pseudo-nitzschia granii distinctly differentially expresses
      genes encoding proteins involved in iron-independent photosynthetic electron
      transport, urea acquisition and vitamin synthesis. We show that P. granii is
      unique among studied diatoms in its physiology stemming from distinct cellular
      responses, which may underlie its ability to subsist in low iron regions and
      rapidly bloom to outcompete other diatom taxa following iron enrichment.

PMID- 30117244
TI  - Highly Regioselective Domino Benzannulation Reaction of Buta-1,3-diynes To
      Construct Irregular Nanographenes.
AB  - The properties of nanographenes can be tuned by changing their shapes, therefore
      the development of new methods suitable for the synthesis of various
      nanographenes is highly desirable. Described herein is an intramolecular InCl3
      /AgNTf2 -catalyzed regioselective domino benzannulation reaction of buta-1,3
      diynes to build irregular nanographenes. Different nanographene compounds were
      easily obtained in moderate to high yields through careful design of the
      precursor compounds. This new domino reaction was successfully applied to a
      fourfold alkyne benzannulation of dimethoxy-1,1'-binaphthalene derivatives to
      arrive at novel chiral butterfly ligand precursors. The regioselectivity of the
      benzannulation reaction was unambiguously confirmed by X-ray crystallography.
      Moreover, this new method enables us to synthesize different nanographene isomers
      and study their optical properties as a function of shape.

PMID- 30117246
TI  - Intraoperative diagnosis of a duplicated cystic duct.

PMID- 30117245
TI  - Evaluating the effectiveness of a nutrition assistant role in a head and neck
      cancer clinic.
AB  - AIM: Acute toxicities secondary to (chemo)radiation for head and neck cancer can
      substantially impact nutritional intake. Nutrition is usually managed by
      dietitians, although time constraints may limit capacity to sufficiently deal
      with complex nutritional issues. The aim of the present study was to determine
      the effectiveness of a nutrition assistant performing screening and intervention
      of patients in a multidisciplinary head and neck clinic. METHODS: A model of care
      was developed to guide nutrition assistant practice within the clinic, with
      training provided to nutrition assistants prior to the clinic's implementation.
      Outcomes, including amount of dietitian time managing high risk patients, weight
      change over the duration of treatment, timing of initiation of enteral feeding
      and patient satisfaction were compared with pre- and post-implementation of the
      nutrition assistant role. RESULTS: Ninety-one patients were included, 43 pre
      implementation and 48 post-implementation. Overall, (n = 21, 44%) of patients met
      criteria for nutrition assistant screening or intervention. Mean weight change
      between groups was comparable both during (-5.6% vs -4.7%, P = 0.3) and post
      radiotherapy (-6.6% vs -6.49%, P = 0.9). Following implementation of the role
      significant improvement was found for overall patient satisfaction (4.0 +/- 1.1
      vs 4.6 +/- 0.61, P = 0.03), and the dimensions: patient-perceived benefit (3.8 +/
      0.69 vs 4.4 +/- 0.62, P < 0.01) and dietitian/nutrition-assistant interpersonal
      skills (3.91 +/- 1.1 vs 4.6 +/- 0.55, P = 0.02). CONCLUSIONS: The nutrition
      assistant role resulted in improved patient satisfaction and maintenance of
      nutritional outcomes demonstrating the effectiveness of this role in supporting
      the management of head and neck cancer patients within a multidisciplinary
      treatment clinic.

PMID- 30117247
TI  - H2 Oxidation Electrocatalysis Enabled by Metal-to-Metal Hydrogen Atom Transfer: A
      Homolytic Approach to a Heterolytic Reaction.
AB  - Oxidation of H2 in a fuel cell converts the chemical energy of the H-H bond into
      electricity. Electrocatalytic oxidation of H2 by molecular catalysts typically
      requires one metal to perform multiple chemical steps: bind H2 , heterolytically
      cleave H2 , and then undergo two oxidation and two deprotonation steps. The
      electrocatalytic oxidation of H2 by a cooperative system using Cp*Cr(CO)3 H and
      [Fe(diphosphine)(CO)3 ]+ has now been invetigated. A key step of the proposed
      mechanism is a rarely observed metal-to-metal hydrogen atom transfer from the Cr
      H complex to the Fe, forming an Fe-H complex that is deprotonated and then
      oxidized electrochemically. This "division of chemical labor" features Cr
      interacting with H2 to cleave the H-H bond, while Fe interfaces with the
      electrode. Neither metal is required to heterolytically cleave H2 , so this
      system provides a very unusual example of a homolytic reaction being a key step
      in a molecular electrocatalytic process.

PMID- 30117248
TI  - Natural hybridization among Quercus glabrescens, Q. rugosa and Q. obtusata
      (Fagaceae): Microsatellites and secondary metabolites markers.
AB  - Natural hybridization has significant ecological, genetic and evolutionary
      consequences altering morphological and chemical characters of individuals.
      Quercus glabrescens, Q. rugosa and Q. obtusata are white oak species well
      separated by their morphological characters when they occur in allopatry in
      Mexican temperate forests. However, in sympatry, individuals with atypical
      morphology have been observed, suggesting hybridization events. In this study, we
      determined with microsatellites and secondary metabolites if interspecific gene
      flow occurs when these three-oak species coexist in sympatry. In total, 180
      individuals belonging to seven populations [three allopatric (one for each
      parental species) and four sympatric sites] were analyzed. Allopatric populations
      represent well defined genetic groups and the sympatric populations showed
      genetic evidence of hybridization between Q. glabrescens * Q. rugosa and Q.
      glabrescens * Q. obtusata. The hybridization percentage varied between sites and
      combination of involved species. We registered the presence of unique flavonoid
      compounds for Q. glabrescens (caffeic acid and flavonol 2), Q. rugosa (flavonol
      5), Q. obtusata (flavonol 1). Three compounds (quercetin rhamnoside, flavonol 3
      and alkyl coumarate) were expressed in all taxa. Finally, the hybrid genotypes
      identified in this study (Q. glabrescens * Q. rugosa and Q. glabrescens * Q.
      obtusata) showed particular chemical profiles, resulting from combination of
      those of their parental species. These results show that hybridization events
      between these oak species alter chemical expression of secondary metabolites,
      creating a mosaic of resources and conditions that provide the substrate for
      different combinations of foliar-associated species as herbivores, endophytic
      fungi or epiphyte plants. This article is protected by copyright. All rights
      reserved.

PMID- 30117249
TI  - Nanostructured SnS2 Thin Films from Laser Ablated Nanocolloids: Structure,
      Morphology, Optoelectronic and Electrochemical Properties.
AB  - Tin disulfide (SnS2 ) is a binary chalcogenide semiconductor having applications
      in solar cells, energy storage, and optoelectronics. SnS2 thin films were
      deposited by spraying the nanocolloids synthesized by pulsed laser ablation in
      liquid. The structure, morphology, and optoelectronic properties were studied for
      films obtained from two liquid media (ethanol and isopropanol) and after heat
      treatments at various temperatures. X-ray diffraction analysis confirmed the
      hexagonal crystal structure of the films, whereas the 2-H polytype structure was
      identified by micro-Raman spectroscopy. Oxidation states of Sn (4+) and S (2-)
      identified from high resolution X-ray photoelectron spectra confirmed the
      composition and chemical states of the films. The SnS2 thin films exhibited
      distinct porous surface morphologies as the liquid medium in laser ablation was
      varied. All as-prepared and annealed films showed photoluminescence with a high
      intensity peak at 485 nm and a low intensity peak at 545 nm. Thin films annealed
      at 300  degrees C showed improved electrochemical properties upon illumination
      using a blue LED light source. Current-voltage curves recorded in dark and light
      as well as the photoresponse measurements showed their suitability for
      utilization in optoelectronic devices. The results of this study may trigger
      further research towards fabrication of nanostructured thin films in large area
      for optoelectronic and photoelectrochemical applications in an environment
      friendly and cost-effective way.

PMID- 30117250
TI  - Ecological and genomic features of two widespread freshwater picocyanobacteria.
AB  - We present two genomes of widespread freshwater picocyanobacteria isolated by
      extinction dilution from a Spanish oligotrophic reservoir. Based on microscopy
      and genomic properties, both picocyanobacteria were tentatively designated
      Synechococcus lacustris Tous, formerly described as a metagenome assembled genome
      (MAG) from the same habitat, and Cyanobium usitatum Tous, described here for the
      first time. Both strains were purified in unicyanobacterial cultures, and their
      genomes were sequenced. They are broadly distributed in freshwater systems; the
      first seems to be a specialist on temperate reservoirs (Tous, Amadorio, Dexter,
      Lake Lanier, Sparkling), and the second appears to also be abundant in cold
      environments including ice-covered lakes such as Lake Baikal, Lake Erie or the
      brackish Baltic Sea. Having complete genomes provided access to the flexible
      genome that does not assemble in MAGs. We found several genomic islands in both
      genomes, within which there were genes for nitrogen acquisition, transporters for
      a wide set of compounds and biosynthesis of phycobilisomes in both strains. Some
      of these regions of low coverage in metagenomes also included antimicrobial
      compounds, transposases and phage defence systems, including a novel type III
      CRISPR-Cas phage defence system that was only detected in Synechococcus lacustris
      Tous.

PMID- 30117251
TI  - ORCHEM Prizes: I. Fleischer and F. Beuerle / Emil Fischer Medal: T. Bach /
      Leonidas Zervas Award: C. P. R. Hackenberge / Hanwha-Total IUPAC Young Scientist
      Award: A. Walther / Thieme-IUPAC Prize: S. Herzon / Greifswald Research Award: U.
      T. Bornscheuer / Melvin Calvin Award: T. Skrydstrup.

PMID- 30117252
TI  - Intraspecific trait variation and trade-offs within and across populations of a
      toxic dinoflagellate.
AB  - Intraspecific trait diversity can promote the success of a species, as
      complementarity of functional traits within populations may enhance its
      competitive success and facilitates resilience to changing environmental
      conditions. Here, we experimentally determined the variation and relationships
      between traits in 15 strains of the toxic dinoflagellate Alexandrium ostenfeldii
      derived from two populations. Measured traits included growth rate, cell size,
      elemental composition, nitrogen uptake kinetics, toxin production and
      allelochemical potency. Our results demonstrate substantial variation in all
      analysed traits both within and across populations, particularly in nitrogen
      affinity, which was even comparable to interspecific variation across
      phytoplankton species. We found distinct trade-offs between maximum nitrogen
      uptake rate and affinity, and between defensive and competitive traits.
      Furthermore, we identified differences in trait variation between the genetically
      similar populations. The observed high trait variation may facilitate development
      and resilience of harmful algal blooms under dynamic environmental conditions.

PMID- 30117253
TI  - Canine T cell lymphoma treated with lomustine, vincristine, procarbazine, and
      prednisolone chemotherapy in 35 dogs.
AB  - Canine T cell lymphoma has previously been found to be a poor prognostic
      indicator compared with its B cell counterpart. The cyclophosphamide,
      doxorubicin, vincristine, and prednisolone protocol is widely accepted as a first
      line treatment for canine lymphoma. There have been several studies investigating
      alternative protocols for T cell lymphoma. This study investigated the use of a
      modified lomustine, vincristine, procarbazine and prednisolone protocol as a
      first line treatment in 35 dogs with T Cell lymphoma. Median progression free
      survival (PFS) time for all 35 dogs was 431 days with a 6-month, 1-year, 2-year,
      and 3-year PFS of 69%, 54%, 29%, and 12%. Median survival time (MST) was 507
      days. Twenty-nine dogs attained a complete response and had a median PFS time of
      509 days. Thirty dogs experienced adverse events during the protocol, with 73% of
      these being grade 1 or 2. This protocol has shown increased median PFS time and
      MST compared with previous studies and suggests its use as a first line
      chemotherapy protocol against canine T cell lymphoma.

PMID- 30117254
TI  - Sharp water column stratification with an extremely dense microbial population in
      a small meromictic lake, Trekhtzvetnoe.
AB  - Located on the shore of Kandalaksha Bay (the White Sea, Russia) and previously
      separated from it, Trekhtzvetnoe Lake (average depth 3.5 m) is one of the
      shallowest meromictic lakes known. Despite its shallowness, it features
      completely developed water column stratification with high-density microbial
      chemocline community (bacterial plate) and high rates of major biogeochemical
      processes. A sharp halocline stabilizes the stratification. Chlorobium
      phaeovibrioides dominated the bacterial plate, which reached a density of 2 * 108
      cell ml-1 and almost completely intercepts H2 S diffusion from the anoxic
      monimolimnion. The resulting anoxygenic photosynthesis rate reached 240 MUmol C l
      1 day-1 , exceeding the oxygenic photosynthesis rate in the mixolimnion. The
      rates of other processes are also high, reaching 4.5 MUmol CH4 l-1 day-1 for
      methane oxidation and 35 MUmol S l-1 day-1 for sulfate reduction. Metagenomic
      analysis demonstrated that the Chl. phaeovibrioides population in the bacterial
      plate layer had nearly clonal homogeneity, although some fraction of these cells
      harbour a plasmid. The Chlorobium population was associated with bacteriophages
      that share homology with CRISPR spacers in the host. These features make the
      ecosystem of the Trekhtzvetnoe Lake a valuable model for studying regulation and
      evolution processes in natural high-density microbial systems.

PMID- 30117255
TI  - Presence of diabetic retinopathy is associated with worse 10-year mortality among
      Indigenous Australians in Central Australia: The Central Australian ocular health
      study.
AB  - IMPORTANCE: Diabetes mellitus (DM) is highly prevalent among Indigenous
      Australians and contributes greatly to premature death. The association of
      diabetic retinopathy (DR) with early mortality, however, has not previously been
      reported among Indigenous Australians. BACKGROUND: To investigate associations
      between 10-y mortality and the presence of DR among Indigenous Australians living
      in Central Australia. DESIGN: Prospective cohort study. PARTICIPANTS: A total of
      1257 individuals aged 40 y or older, living in one of 30 remote communities
      within Central Australia were recruited through outreach clinics. METHODS: Fundus
      examination was performed on all patients at recruitment. The presence of any DR
      was recorded. MAIN OUTCOME MEASURES: Mortality rate and cause were obtained at 10
      y, and their association with any DR was determined. RESULTS: Ten-year all-cause
      mortality was found to be 29.3%. Of those with DM but no DR, 24.0% died during
      the 10 y after recruitment, compared with 40.1% for those with any DR (P <
      0.0001). Those who had any DR were 75% more likely to die (hazard ratio [HR]
      1.75; P < 0.0001) and were more likely to die from renal failure (HR 2.71; P =
      0.004) or stroke (HR 5.91; P = 0.026). CONCLUSION AND RELEVANCE: The presence of
      any DR among those with DM, was associated with a 75% greater 10-y all-cause
      mortality rate and were more likely to die from renal failure or stroke. We
      recommend that whenever DR is noted among Indigenous Australians with DM, that
      they be immediately referred for investigation and management of risk factors,
      which might predispose to renal failure and stroke.

PMID- 30117256
TI  - The relative abundance of alkane-degrading bacteria oscillated similarly to a
      sinusoidal curve in an artificial ecosystem model from oil-well products.
AB  - Microbial phylogenetic diversity and species interactions in natural ecosystems
      have been investigated extensively, but our knowledge about their ecological
      roles, community dynamics and succession patterns is far from complete. This
      knowledge is essential to understand the complicated interactions of
      microorganisms in natural ecosystems. Here, an artificial ecosystem model of
      microorganisms was constructed from oil-well products and cultivated in a
      chemostat to investigate the succession pattern of alkane-degrading bacteria, a
      functional population in oil reservoirs. Their abundance was quantified by an
      improved qPCR technique. Our results showed that the phylogenetic structure of
      this artificial ecosystem model is stable during most of the chemostat
      cultivation process, while the genotype structure of alkane-degrading bacteria
      containing alkB genes shifted and their relative abundance oscillated similarly
      to a sinusoidal curve, like the succession pattern of producers in the Lotka
      Volterra model. These results suggest that some theoretical frameworks of
      macroecology may work well in microbial ecosystems and be an efficient tool to
      understand them.

PMID- 30117257
TI  - Mitochondrial genome, comparative analysis and evolutionary insights into the
      entomopathogenic fungus Hirsutella thompsonii.
AB  - Nuclear genomes of two isolates of Hirsutella thompsonii, a pathogen causing
      epizootics among mites, have been reported; in contrast, its mitochondrial genome
      (mitogenome) has remained unknown, limiting our understanding of its evolution.
      Herein, we annotated the first complete mitogenome of H. thompsonii, which
      encoded all standard fungal mitochondrial genes plus three free-standing ORFs.
      Transcriptional analyses validated the expression of most conserved genes and
      revealed some interesting transcription patterns of mitochondrial genes.
      Phylogenetic analyses confirmed its placement in Ophiocordycipitaceae. Comparison
      of five different isolates originally collected from different locations revealed
      mitogenome size variations (60.3-66.4 kb) mainly due to different numbers of
      introns. A total of 15 intron loci were identified, with 11 existing in all 5
      isolates and 4 showing presence/absence dynamics. These introns were most likely
      obtained through horizontal transfer from other fungal organisms. Those common
      introns might have been in H. thompsonii mitogenomes since the divergence of the
      fungus from its putative sister species H. minnesotensis, whereas those dynamic
      introns might have experienced 1-2 gain or loss events. We also detected evidence
      of degeneration for some introns. Overall, our study shed new insights into the
      mitochondrial evolution of the acaropathogenic fungus H. thompsonii.

PMID- 30117258
TI  - The next best thing in factor VIIa.

PMID- 30117259
TI  - Parallel/Opposed Editorial: DMP/residency programs are more sustainable than MPAs
      for the future of the medical physics profession.

PMID- 30117260
TI  - Response rate to a single dose of vinblastine administered to dogs with treatment
      naive multicentric lymphoma.
AB  - Vincristine is included in vincristine, cyclophosphamide, doxorubicin and
      prednisone (CHOP) chemotherapy protocols, which are the gold-standard treatment
      for high-grade canine lymphoma. Vincristine can result in relatively high rates
      of gastrointestinal toxicity, whereas vinblastine is generally well tolerated and
      thus may represent an under-utilized and minimally toxic alternative to
      vincristine. Our objective was to determine the response rate and toxicity
      associated with a single dose of vinblastine administered to dogs with treatment
      naive, intermediate to large-cell, multicentric lymphoma. Twenty client-owned
      dogs were enrolled with signed owner consent. A Simon's minimax, phase II, two
      stage trial was performed to test the efficacy of vinblastine administered at 2
      mg/m2 IV followed by a pilot trial of vinblastine at 2.5 mg/m2 . No dogs were
      administered concurrent steroids or other chemotherapy. One out of 14 dogs
      receiving vinblastine at 2 mg/m2 demonstrated a partial response. Three out of
      five dogs demonstrated a partial response to vinblastine at 2.5 mg/m2 .
      Gastrointestinal toxicity was infrequent and low grade for both groups. The
      majority of dogs (80%) in the 2.5 mg/m2 dosing group developed neutropenia 1-week
      post administration. Vinblastine was well tolerated but minimally efficacious at
      a dose of 2 mg/m2 IV in dogs with treatment-naive, multicentric lymphoma. Because
      of poor response rates, treatment at this dose is not recommended. A small subset
      of dogs administered 2.5 mg/m2 had significantly improved response rates (P =
      0.04), suggesting that higher doses may have improved efficacy, although further
      research is indicated to confirm these preliminary findings.

PMID- 30117262
TI  - Metabolic specialization of denitrifiers in permeable sediments controls N2 O
      emissions.
AB  - Coastal oceans receive large amounts of anthropogenic fixed nitrogen (N), most of
      which is denitrified in the sediment before reaching the open ocean. Sandy
      sediments, which are common in coastal regions, seem to play an important role in
      catalysing this N-loss. Permeable sediments are characterized by advective
      porewater transport, which supplies high fluxes of organic matter into the
      sediment, but also leads to fluctuations in oxygen and nitrate concentrations.
      Little is known about how the denitrifying communities in these sediments are
      adapted to such fluctuations. Our combined results indicate that denitrification
      in eutrophied sandy sediments from the world's largest tidal flat system, the
      Wadden Sea, is carried out by different groups of microorganisms. This
      segregation leads to the formation of N2 O which is advectively transported to
      the overlying waters and thereby emitted to the atmosphere. At the same time, the
      production of N2 O within the sediment supports a subset of Flavobacteriia which
      appear to be specialized on N2 O reduction. If the mechanisms shown here are
      active in other coastal zones, then denitrification in eutrophied sandy sediments
      may substantially contribute to current marine N2 O emissions.

PMID- 30117263
TI  - Ethnic benign neutropenia: A phenomenon finds an explanation.
AB  - Ethnic benign neutropenia (ENP) is the most common form of neutropenia (NP)
      worldwide, if an absolute blood neutrophil count (ANC) of < 1.5 G/L is used as
      definition. In 2009, ENP was associated with a gene variation in the ACKR1/DARC
      gene, the same variation that also confers the Duffy-null trait. In 2017, a novel
      mechanism for ENP was introduced, questioning if ENP is a true neutropenic state,
      when the body's total neutrophil count (TBNC) is concerned. Here, we summarize
      the current knowledge of ENP, asking (1) How well does the peripheral blood ANC
      predict the TBNC? (2) Can we improve methods for assessing TBNC? (3) Will
      estimates of TBNC predict infection propensity and reduce the need for further,
      costly workup?

PMID- 30117261
TI  - A patient-derived explant (PDE) model of hormone-dependent cancer.
AB  - Breast and prostate cancer research to date has largely been predicated on the
      use of cell lines in vitro or in vivo. These limitations have led to the
      development of more clinically relevant models, such as organoids or murine
      xenografts that utilize patient-derived material; however, issues related to low
      take rate, long duration of establishment, and the associated costs constrain use
      of these models. This study demonstrates that ex vivo culture of freshly resected
      breast and prostate tumor specimens obtained from surgery, termed patient-derived
      explants (PDEs), provides a high-throughput and cost-effective model that retains
      the native tissue architecture, microenvironment, cell viability, and key
      oncogenic drivers. The PDE model provides a unique approach for direct evaluation
      of drug responses on an individual patient's tumor, which is amenable to analysis
      using contemporary genomic technologies. The ability to rapidly evaluate drug
      efficacy in patient-derived material has high potential to facilitate
      implementation of personalized medicine approaches.

PMID- 30117264
TI  - Expression of the Hippo signalling effectors YAP and TAZ in canine mammary gland
      hyperplasia and malignant transformation of mammary tumours.
AB  - Canine mammary tumours (CMTs) are common neoplasms in dogs that feature many of
      the clinical, genetic and molecular characteristics of human breast cancer.
      Despite their high metastatic potential, few adjuvant chemotherapeutic treatment
      options exist for malignant CMTs, and the development of novel, targeted
      pharmacological approaches will require a better understanding of their
      pathogenesis. As recent evidence suggests that dysregulated Hippo signalling is
      involved in the development and progression of breast cancer, we sought to
      determine if this pathway could also play a role in CMT. The expression of the
      Hippo signalling effectors YAP and TAZ was analysed by immunoblotting and
      immunohistochemistry in samples including normal mammary gland, lobular
      hyperplasia, benign tumours and malignant tumours of all grades. We found a
      significant increase in TAZ (but not YAP) expression occurred in lobular
      hyperplasia relative to normal mammary gland, suggesting a role for TAZ in non
      neoplastic epithelial proliferation. Nuclear expression of both TAZ and YAP were
      significantly higher in malignant tumours than in benign ones, suggesting that
      Hippo dysregulation could play a role in CMT malignant transformation. No
      differences in YAP or TAZ expression were detected between grades of malignant
      tumours. Together, our results indicate that alterations in Hippo signalling may
      play a role in the pathogenesis of CMT, in a manner similar to breast cancer.
      Hippo pathway components may therefore represent targets for the development of
      novel chemotherapeutic agents that could be useful for the treatment of both the
      human and canine diseases.

PMID- 30117266
TI  - Overlapping radiofrequency ablation planning and robot-assisted needle insertion
      for large liver tumors.
AB  - BACKGROUND: We aimed at facilitating percutaneous radiofrequency ablation (RFA)
      for large tumors with accurate overlapping ablation planning and robot-assisted
      needle insertion from a single incision port (SIP). METHODS: We developed a
      personalized and quantitative RFA planning method to obtain multiple needle
      overlapping ablation planning through a single incision. A robot with a remote
      center of motion mechanism was designed to perform needle insertions through a
      SIP according to the planning. RESULTS: Numerical and visual evaluation showed
      that the planning could yield nearly full coverage over large tumors and greatly
      reduce both ablation times and the ablations of normal tissues. Ex vivo and in
      vivo experiments showed that our robot-assisted needle insertion system was
      capable of conducting the RFA procedure in large liver tumors from a SIP.
      CONCLUSIONS: Robot-assisted RFA needle insertions from a SIP makes RFA treatment
      for large tumors more minimally invasive, predictable, and repeatable.

PMID- 30117267
TI  - Ultrathin Molybdenum Dioxide Nanosheets as Uniform and Reusable Surface-Enhanced
      Raman Spectroscopy Substrates with High Sensitivity.
AB  - Metal oxides have advantages over the traditional noble metals to be used as
      substrate materials for surface-enhanced Raman spectroscopy (SERS) with low cost,
      versatility, and biocompatibility, but their enhancement factors are generally
      quite low with a poor limit of detection. Here, ultrathin molybdenum dioxide
      (MoO2 ) nanosheets synthesized by chemical vapor deposition demonstrated in large
      area are used as SERS substrates with superior signal uniformity in the whole
      area with a limit of detectable concentration down to 4 * 10-8 m and enhancement
      factor up to 2.1 * 105 , exceeding that of 2D materials and comparable to that of
      noble metal films. More practically important, the planar MoO2 substrate is more
      robust than noble metals and shows excellent reusability and uniformity, which is
      usually prohibited for nanostructured or nanoparticle-based metal oxide
      substrates. The enhancement is mainly attributed to the surface plasmon resonance
      effect as evidenced by the first principle calculations and UV-vis absorption
      spectroscopy characterization, which can be further increased by decreasing the
      thickness of the MoO2 nanosheets. The overall superior performance makes the MoO2
      nanosheets an ideal substrate for practical SERS applications.

PMID- 30117265
TI  - A clinical update on tuberous sclerosis complex-associated neuropsychiatric
      disorders (TAND).
AB  - Tuberous sclerosis complex (TSC) is associated with a wide range of behavioral,
      psychiatric, intellectual, academic, neuropsychological, and psychosocial
      difficulties, which are often underdiagnosed and undertreated. Here, we present a
      clinical update on TSC-associated neuropsychiatric disorders, abbreviated as
      "TAND," to guide screening, diagnosis, and treatment in practice. The review is
      aimed at clinical geneticists, genetic counselors, pediatricians, and all
      generalists involved in the assessment and treatment of children, adolescents and
      adults with TSC, and related disorders. The review starts with a summary of the
      construct and levels of TAND, before presenting up-to-date information about each
      level of investigation. The review concludes with a synopsis of current and
      future TAND research.

PMID- 30117269
TI  - Triaryl Pyrazole Toll-Like Receptor Signaling Inhibitors: Structure-Activity
      Relationships Governing Pan- and Selective Signaling Inhibitors.
AB  - The immune system uses members of the toll-like receptor (TLR) family to
      recognize a variety of pathogen- and host-derived molecules in order to initiate
      immune responses. Although TLR-mediated, pro-inflammatory immune responses are
      essential for host defense, prolonged and exaggerated activation can result in
      inflammation pathology that manifests in a variety of diseases. Therefore, small
      molecule inhibitors of the TLR signaling pathway might have promise as anti
      inflammatory drugs. We previously identified a class of triaryl pyrazole
      compounds that inhibit TLR signaling by modulation of the protein-protein
      interactions essential to the pathway. We have now systematically examined the
      structural features essential for inhibition of this pathway, revealing
      characteristics of compounds that inhibited all TLRs tested (pan-TLR signaling
      inhibitors) as well as compounds that selectively inhibited certain TLRs. These
      findings reveal interesting classes of compounds that could be optimized for
      particular inflammatory diseases governed by different TLRs.

PMID- 30117270
TI  - At the precipice.

PMID- 30117268
TI  - A New Way to Promote Molecular Drug Release during Medical Treatment: A
      Polyelectrolyte Matrix on a Piezoelectric-Dielectric Energy Conversion Substrate.
AB  - Enhanced drug releases in a timely manner during urgent medical treatments would
      significantly enhance the prognosis of patients. Inspired by the facilitated
      molecular transports by the potentials, an enhanced drug release strategy driven
      by mechanical disturbances that widely exist in medical treatment processes is
      proposed. This strategy is enabled by a functional material comprised of
      multilayers of dendrimers as the drug reservoir, which are built on a
      piezoelectric-dielectric flexible film with reduced graphene oxide fillers. The
      generated voltages are higher and last longer than that in regular piezoelectric
      films. Photochemical crosslinking leads to a stable drug matrix which is even
      sustained in electric fields and high ionic strengths. The device enhances
      releases of positively, negatively, and zwitterionically charged molecules in
      response to mechanical stimuli and supports high cell viabilities. An
      illustrative application is demonstrated by preparing the material on the surface
      of a gastric lavage tube. The results show that the release of antiemetic drug
      increased by 200% within 60 min in response to forces mimicking human swallowing.
      This study contributes an integrative material that can realize electrically
      triggered releases that are previously only realized using complicated
      electrochemical setups. It is believed that this material can facilitate medicine
      applications in various emergent situations.

PMID- 30117271
TI  - Licensing examination scores and fellowship selection.

PMID- 30117272
TI  - Virtual reality simulation of robotic transsphenoidal brain tumor resection:
      Evaluating dynamic motion scaling in a master-slave system.
AB  - BACKGROUND: Integrating simulators with robotic surgical procedures could assist
      in designing and testing of novel robotic control algorithms and further enhance
      patient-specific pre-operative planning and training for robotic surgeries.
      METHODS: A virtual reality simulator, developed to perform the transsphenoidal
      resection of pituitary gland tumours, tested the usability of robotic interfaces
      and control algorithms. It used position-based dynamics to allow soft-tissue
      deformation and resection with haptic feedback; dynamic motion scaling control
      was also incorporated into the simulator. RESULTS: Neurosurgeons and residents
      performed the surgery under constant and dynamic motion scaling conditions (CMS
      vs DMS). DMS increased dexterity and reduced the risk of damage to healthy brain
      tissue. Post-experimental questionnaires indicated that the system was well
      evaluated by experts. CONCLUSION: The simulator was intuitively and realistically
      operated. It increased the safety and accuracy of the procedure without affecting
      intervention time. Future research can investigate incorporating this simulation
      into a real micro-surgical robotic system.

PMID- 30117273
TI  - Medical physics 3.0 versus 1.0: A case study in digital radiography quality
      control.
AB  - PURPOSE: The study illustrates how a renewed approach to medical physics, Medical
      Physics 3.0 (MP3.0), can identify performance decrement of digital radiography
      (DR) systems when conventional Medical Physics 1.0 (MP1.0) methods fail. METHODS:
      MP1.0 tests included traditional annual tests plus the manufacturer's automated
      Quality Assurance Procedures (QAP) of a DR system before and after a
      radiologist's image quality (IQ) complaint repeated after service intervention.
      Further analysis was conducted using nontraditional MP3.0 tests including
      longitudinal review of QAP results from a 15-yr database, exposure-dependent
      signal-to-noise (SNR2 ), clinical IQ, and correlation with the institutional
      service database. Clinical images were analyzed in terms of IQ metrics by the
      Duke University Clinical Imaging Physics Group using previously validated
      software. RESULTS: Traditional metrics did not indicate discrepant system
      performance at any time. QAP reported a decrease in contrast-to-noise ratio (CNR)
      after detector replacement, but remained above the manufacturer's action limit.
      Clinical images showed increased lung noise (Ln), mediastinum noise (Mn), and
      subdiaphragm-lung contrast (SLc), and decreased lung gray level (Lgl) following
      detector replacement. After detector recalibration, QAP CNR improved, but did not
      return to previous levels. Lgl and SLc no longer significantly differed from
      before detector recalibration; however, Ln and Mn remained significantly
      different. Exposure-dependent SNR2 documented the detector operating within
      acceptable limits 9 yr previously but subsequently becoming miscalibrated
      sometime before four prior annual tests. Service records revealed catastrophic
      failure of the computer containing the original detector calibration from 11 yr
      prior. It is likely that the incorrect calibration backup file was uploaded at
      that time. CONCLUSIONS: MP1.0 tests failed to detect substandard system
      performance, but MP3.0 methods determined the root cause of the problem. MP3.0
      exploits the wealth of data with more sensitive performance indicators. Data
      analytics are powerful tools whose proper application could facilitate early
      intervention in degraded system performance.

PMID- 30117274
TI  - Nanosilver-Enabled Food Storage Container Tradeoffs: Environmental Impacts Versus
      Food Savings Benefit, Informed by Literature.
AB  - Globally, thousands of tons of food are lost each year due to spoilage and
      degraded quality. This loss is a current critical issue that must be addressed to
      ensure adequate food supply for the growing world population; the use of
      technology and regulatory practices are avenues to a solution. One considered
      approach is the reduction of the microorganism population on the surface of food
      products to delay spoilage through the use of antimicrobials. One current method
      is the use of the antimicrobial properties of nanoscale silver (nAg) particles to
      prolong the freshness of stored food by reducing the bacteria present. Nanoscale
      silver-enabled food storage containers present a potential solution to the food
      loss problem; nevertheless, their environmental and human health effects have
      been questioned by the scientific community. Literature is used to generate data
      for the life cycle impact assessment of these types of products and their
      corresponding environmental effects. The benefits of nAg-enabled food storage
      containers are considered with respect to their potential to extend the shelf
      life of stored food and prevent food spoilage. The results illustrate that the
      environmental effects of nano-enabling food storage containers with silver is
      small (when the initial silver concentration is relatively low, less than 1% by
      mass) compared with the overall environmental effects of food storage containers
      and also relatively small compared with the environmental effects of producing
      the stored food. This finding suggests that the added environmental burden of
      nano-enabling food storage containers may be small when compared with the
      environmental burden of food losses. Integr Environ Assess Manag 2018;14:769-776.
      (c) 2018 SETAC.

PMID- 30117275
TI  - Retrospective evaluation of a decision-support algorithm (MIPOGG) for genetic
      referrals for children with neuroblastic tumors.
AB  - BACKGROUND: Neuroblastoma is the most common pediatric extracranial solid tumor.
      Germline pathogenic variants in ALK and PHOX2B, as well as other cancer
      predisposition genes, are increasingly implicated in the pathogenesis of
      neuroblastic tumors. A challenge for clinicians is the identification of children
      with neuroblastoma who require genetics evaluation for underlying cancer
      predisposition syndromes (CPS). PROCEDURE: We developed a decisional algorithm
      (MIPOGG) to identify which patients with neuroblastic tumors have an increased
      likelihood of an underlying CPS. This algorithm, comprising 11 Yes/No questions,
      evaluates features in the tumor, personal and family history that are suggestive
      of an underlying CPS. We assessed the algorithm's performance in a retrospective
      cohort. RESULTS: Two hundred and nine of 278 consecutive patients with
      neuroblastic tumors at The Hospital for Sick Children (2007-2016) had sufficient
      clinical data for retrospective application of the decisional algorithm. Fifty
      one of 209 patients had been referred to genetics for CPS evaluation; 6/51 had a
      genetic or clinical confirmation of a CPS. The algorithm correctly identified all
      six children (Beckwith-Wiedemann (n = 2), Fanconi anemia, RB1, PHOX2B, chromosome
      duplication involving ALK) as requiring a genetic evaluation by using clinical
      features present at diagnosis. The level of agreement between the algorithm and
      physicians was 83.9%, with 15 more patients identified by the algorithm than by
      physicians as requiring a genetics referral. CONCLUSIONS: This decisional
      algorithm appropriately detected all patients who, following genetic evaluation,
      were confirmed to have a CPS and may improve the detection of CPS in patients
      with neuroblastic tumors compared with current practice.

PMID- 30117276
TI  - Analysis of the putative tumor suppressor gene cdkn2ab in pigment cells and
      melanoma of Xiphophorus and medaka.
AB  - In humans, the CDKN2A locus encodes two transcripts, INK4A and ARF. Inactivation
      of either one by mutations or epigenetic changes is a frequent signature of
      malignant melanoma and one of the most relevant entry points for melanomagenesis.
      To analyze whether cdkn2ab, the fish ortholog of CDKN2A, has a similar function
      as its human counterpart, we studied its action in fish models for human
      melanoma. Overexpression of cdkn2ab in a Xiphophorus melanoma cell line led to
      decreased proliferation and induction of a senescence-like phenotype, indicating
      a melanoma-suppressive function analogous to mammals. Coexpression of Xiphophorus
      cdkn2ab in medaka transgenic for the mitfa:xmrk melanoma-inducing gene resulted
      in full suppression of melanoma development, whereas CRISPR/Cas9 knockout of
      cdkn2ab resulted in strongly enhanced tumor growth. In summary, this provides the
      first functional evidence that cdkn2ab acts as a potent tumor suppressor gene in
      fish melanoma models.

PMID- 30117277
TI  - Short-term to long-term extrapolation of lethal effects of an herbicide on the
      marine mysid shrimp Americamysis Bahia by use of the General Unified Threshold
      Model of Survival (GUTS).
AB  - Risk assessments for plant protection products and their active ingredients that
      are based on standard laboratory tests performed under constant exposure
      conditions may result in an overestimation of risks because exposure in the
      environment is often characterized by a few short peaks. Here, the General
      Unified Threshold Model of Survival (GUTS) was used to conduct a refined risk
      assessment for the herbicide tembotrione and its effects on the marine
      invertebrate Americamysis bahia, for which the standard chronic effect assessment
      failed. The GUTS model was first calibrated with time-to-effect and concentration
      response data from 2 independent acute experiments with A. bahia. Model
      parameters for both toxicodynamic assumptions of stochastic death (SD) and
      individual tolerance (IT) were estimated with the reduced GUTS model (GUTS-RED)
      using the scaled internal concentration as a dose metric. Both the calibrated
      GUTS-RED-SD and GUTS-RED-IT models described survival dynamics well. Model
      validation using datasets of 2 independent chronic tests yielded robust
      predictions of long-term toxicity of tembotrione on A. bahia, with GUTS-RED-IT
      being more reliable than GUTS-RED-SD. The validated model was subsequently used
      to predict survival from time-variable exposure profiles, as derived from the
      FOrum for Co-ordination of pesticide fate models and their USe (FOCUS). Because
      ecotoxicological independence of peaks had not been empirically verified, the
      link between exposure and effects was assessed with complete exposure profiles.
      Effect thresholds resulting from different peak exposure concentrations and
      durations were determined with GUTS and directly compared with the exposure
      concentrations from the FOCUS surface water scenarios. The derived values were
      higher than the predicted FOCUS critical concentrations. Additionally, comparing
      the areas under the curve (AUCs) derived with GUTS for multiple peak exposure
      profiles to those from FOCUS revealed significant additional safety margins,
      demonstrating that only unrealistically high exposure concentrations would
      produce significant effects. In conclusion, no unacceptable effects of
      tembotrione on aquatic invertebrates under realistic environmental exposure
      conditions are expected. Integr Environ Assess Manag 2018;00:000-000. (c) 2018
      SETAC.

PMID- 30117278
TI  - 3D microvascular analysis reveals irregularly branching blood vessels in the
      hyperpigmented skin of solar lentigo.

PMID- 30117279
TI  - Homozygous intronic MITF mutation causes severe Waardenburg syndrome type 2A.

PMID- 30117280
TI  - Long-term prognosis after biliary stenting for common bile duct stones in high
      risk elderly patients.
AB  - OBJECTIVE: To evaluate the long-term outcomes of complete common bile duct (CBD)
      stone removal and biliary stenting in elderly patients (>=85 years) with CBD
      stones. METHODS: We retrospectively examined 65 patients who underwent complete
      CBD stone removal (the duct clearance group) and 40 patients who underwent
      biliary stenting (the biliary stenting group) between July 2006 and March 2016.
      To reduce selection bias, we also conducted a propensity score matching analysis
      and generated 30 pairs of patients. Cholangitis recurrence-free survival and
      overall survival were compared between the two groups and independent prognostic
      factors of survival were identified by univariate and multivariate analyses.
      RESULTS: Cholangitis recurrence-free survival was significantly better in the
      duct clearance group than in the biliary stenting group (P < 0.001). Their
      overall survival did not significantly differ after propensity score matching (P
      = 0.388). In all cohorts, univariate analysis demonstrated that poor performance
      status and biliary stenting were factors of poor prognosis, and in multivariate
      analysis only performance status remained associated with poor prognosis for
      survival. Similarly, in the propensity score-matched cohort, only performance
      status independently predicted poorer survival (hazard ratio [HR] 2.726, 95%
      confidence interval [CI] 1.105-6.675, P = 0.029). The choice of endoscopic
      treatment was not a significant factor associated with prognosis (HR 1.354, 95%
      CI 0.678-2.701, P = 0.391). CONCLUSIONS: Biliary stenting was similar to complete
      stone removal in terms of prognosis for long-term survival. Biliary stenting for
      CBD stones could be an effective therapeutic tool in high-risk elderly patients.

PMID- 30117281
TI  - Long-term outcome of group D patients with negative serum anti-Helicobacter
      pylori antibody and positive serum pepsinogen test in healthy Koreans.
AB  - OBJECTIVE: The aim of this study was to assess the clinical characteristics and
      long-term outcomes of group D patients (negative H. pylori antibodies and
      positive pepsinogen level). METHODS: Group D patients were divided into two
      groups, that is, the limited endoscopic atrophic gastritis (EAG) group with EAG
      confined to the antrum and angle (C1 and C2) and the advanced EAG group with
      gastric body-involved EAG (C3 to O3). We compared the progression of precursor
      lesions and the occurrence of gastric neoplasms between the two groups. RESULTS:
      Among 107 group D patients, the advanced EAG group (n = 60) was elder and had a
      lower pepsinogen I level and a lower pepsinogen I to II ratio (PGI/II) than the
      limited EAG group (n = 47). Among the 52 patients who underwent a follow-up
      endoscopy, three gastric neoplasms were detected (one in the limited and two in
      the advanced EAG groups). During a median follow-up of 44 months, 10 (43.5%)
      patients in the limited and 13 (52.0%) in the advanced EAG groups showed EAG
      progression or newly occurred intestinal metaplasia. A family history of GC (odds
      ratio [OR] 44.974, 95% confidence interval [CI] 1.360-1487.087), a lower PGI/II
      (OR 0.247, 95% CI 0.085-0.717) and a longer follow-up duration (OR 1.832, 95% CI
      1.200-2.796) increased the risk of progression. CONCLUSION: A family history of
      GC and low baseline PGI/II were independently associated with an increased risk
      of progression of precursor lesions of GC.

PMID- 30117282
TI  - Patients' expectations and experiences of eating behaviour change after bariatric
      procedures.
AB  - Patients' pre-surgical expectations and post-surgical experiences of eating
      related behaviour change after bariatric surgery may vary by procedure and time
      since surgery. To investigate this, data were coded from 206 Australian adults
      >=2 months post-Roux-en-Y gastric bypass (RYGB; 17%), adjustable gastric band
      (AGB; 23%) or vertical sleeve gastrectomy (VSG; 60%) who completed an online
      questionnaire including open-ended questions about pre-surgical eating-related
      expectations and post-surgical experiences. Participants were 94% female, and
      mean age was 45.9 (SD = 10.0). Average time since surgery varied (AGB: 69.6
      months; RYGB: 22.8; and VSG: 17.8). The proportions reporting any one or more
      'positive' (healthy, helpful or desired; RYGB 82%; AGB 76%; and VSG 84%) or any
      one or more 'negative' (unhealthy, unhelpful or unwanted; RYGB 46%; AGB 46%; and
      VSG 42%) post-surgical eating-related experience did not differ by procedure.
      Negative experiences were more often reported at >=18 months than 2 to <18 months
      (P = 0.035). After both VSG and AGB, but not RYGB, reporting any one or more
      positive eating-related experience was related to better outcomes (VSG: in mental
      health; AGB: in weight loss, physical health, satisfaction) and negative
      experiences were linked to poorer outcomes (VSG: in mental health, satisfaction;
      AGB: in mental and physical health, satisfaction). Reporting any one or more
      positive experience was related to better mental health improvement at 2 to <18
      months and greater satisfaction at 18+ months post-surgery. The findings
      highlight the necessity of long-term, multidisciplinary patient care and further
      investigation into impacts of eating-related experiences on outcomes, with
      attention to procedure-based and temporal effects.

PMID- 30117283
TI  - Using Bayesian networks to predict risk to estuary water quality and patterns of
      benthic environmental DNA in Queensland.
AB  - Predictive modeling can inform natural resource management by representing
      stressor-response pathways in a logical way and quantifying the effects on
      selected endpoints. This study demonstrates a risk assessment model using the
      Bayesian network relative risk model (BN-RRM) approach to predict water quality
      and, for the first time, eukaryote environmental DNA (eDNA) data as a measure of
      benthic community structure. Environmental DNA sampling is a technique for
      biodiversity measurements that involves extracting DNA from environmental
      samples, amplicon sequencing a targeted gene, in this case the 18s rDNA gene
      (which targets eukaryotes), and matching the sequences to organisms. Using a
      network of probability distributions, the BN-RRM model predicts risk to water
      quality objectives and the relative richness of benthic taxa groups in the Noosa,
      Pine, and Logan estuaries in Southeast Queensland (SEQ), Australia. The model
      predicts Dissloved Oxygen more accurately than the chlorophyll a water quality
      endpoint and photosynthesizing benthos more accurately than heterotrophs. Results
      of BN-RRM modeling given current inputs indicate that the water quality and
      benthic assemblages of the Noosa are relatively homogenous across all sub risk
      regions, and that the Noosa has a 73%-92% probability of achieving water quality
      objectives, indicating a low relative risk. Conversely, the Middle Logan, Middle
      Pine, and Lower Pine regions are much less likely to meet objectives (15%-55%
      probability), indicating a relatively higher risk to water quality in those
      regions. The benthic community richness patterns associated with risk in the
      Noosa are high Diatom relative richness and low Green Algae relative richness.
      The only benthic pattern consistently associated with the relatively higher risk
      to water quality is high richness of fungi species. The BN-RRM model provides a
      basis for future predictions and adaptive management at the direction of resource
      managers. Integr Environ Assess Manag 2018;00:000-000. (c) 2018 SETAC.

PMID- 30117284
TI  - Advancing alternatives assessment for safer chemical substitution: A research and
      practice agenda.
AB  - Alternatives assessment has emerged as a science policy field that supports the
      evaluation and adoption of safer chemistries in manufacturing processes and
      consumer products. The recent surge in the development and practice of
      alternatives assessment has revealed notable methodological challenges. Spurred
      by this need, we convened an informal community of practice comprising industry
      experts, academics, and scientists within government and nongovernmental
      organizations to prioritize a research and practice agenda for the next 5 years
      that, if implemented, would significantly advance the field of alternatives
      assessment. With input from over 40 experts, the agenda outlines specific needs
      to advance methods, tools, and guidance in 5 critical areas: hazard assessment,
      comparative exposure characterization, life cycle considerations, decision
      making, and professional practice. Fifteen research and practice needs were
      identified, ranging from relatively simple efforts to define a minimum hazard
      data set to the development of more complex performance and decision-analytic
      methods and data integration tools. Some research needs involve adapting existing
      approaches to the alternatives assessment context, while others will require the
      development of entirely new methods and tools. The proposed research and practice
      agenda is ambitious. Implementing it will require expanding the current network
      of researchers from academia, government, and industry, as well as increased
      funding for methodological, application, and evaluation research. Integr Environ
      Assess Manag 2018;00:000-000. (c) 2018 SETAC.

PMID- 30117285
TI  - Communication training for inter-specialty clinicians.
AB  - BACKGROUND: Inter-specialty clinicians often co-lead family conferences for
      hospitalised patients. Families frequently report receiving different messages
      from different clinicians. We developed a communication training workshop that
      crosses disciplines and co-trains clinicians in one setting to create a culture
      of delivering a unified message. METHODS: We developed a 2-day paediatric
      communication skills workshop to teach the skills necessary to conduct a family
      conference. The workshop was targeted at nurse-practitioners and faculty
      clinicians representing the different specialties that co-manage children in an
      intensive care unit. Our primary outcomes were learner self-assessment of skills
      attainment and workshop satisfaction. We also evaluated the feasibility of
      recruiting busy clinicians. RESULTS: Fifteen clinicians, including eight critical
      care faculty members (80% of eligible participants), three subspecialty faculty
      members (100% of eligible participants) and four nurse-practitioners (100% of
      eligible participants), participated. Learners' self-reported confidence improved
      in all communication metrics assessed. From pre- to post-workshop, confidence
      increased from 39% to 94% for 'giving bad news' (p < 0.05), from 50% to 83% for
      'conducting a family conference' (p < 0.05), and from 39% to 100% for 'eliciting
      a family's values/preferences (p < 0.05). Every learner rated the workshop as
      important to their clinical practice and 100% would strongly recommend it to
      others. All reported the time commitment was not burdensome and 74% would choose
      this 2-day format over shorter formats. When clinicians learn together, they are
      more likely to speak the same language when communicating with each other, and
      ultimately to deliver the same message to families CONCLUSIONS: An inter
      specialty communication training workshop for different types of clinician was
      well received. It is feasible to co-train different types of clinician in a joint
      session. When clinicians learn together, they are more likely to speak the same
      language when communicating with each other, and ultimately to deliver the same
      message to families.

PMID- 30117286
TI  - A biopsy-needle compatible varifocal multiphoton rigid probe for depth-resolved
      optical biopsy.
AB  - In this work, we report a biopsy-needle compatible rigid probe, capable of
      performing three-dimensional (3D) two-photon optical biopsy. The probe has a
      small outer diameter of 1.75 mm and fits inside a gauge-14 biopsy needle to reach
      internal organs. A carefully designed focus scanning mechanism has been
      implemented in the rigid probe, which, along with a rapid two-dimensional MEMS
      scanner, enables 3D imaging. Fast image acquisition up to 10 frames per second is
      possible, dramatically reducing motion artifacts during in vivo imaging. Equipped
      with a high-numerical aperture micro-objective, the miniature rigid probe offers
      a high two-photon resolution (0.833 * 6.11 MUm, lateral * axial), a lateral field
      of view of 120 MUm, and an axial focus tuning range of 200 MUm. In addition to
      imaging of mouse internal organs and subcutaneous tumor in vivo, first-of-its
      kind depth-resolved two-photon optical biopsy of an internal organ has been
      successfully demonstrated on mouse kidney in vivo and in situ.

PMID- 30117287
TI  - Development and validation of the Vitiligo Extent Score for a Target Area (VESTA)
      to assess the treatment response of a target lesion.
AB  - Since localized treatment for vitiligo is as essential as systemic treatment, a
      reliable instrument for target evaluation is needed besides those for whole body
      evaluation. We developed the Vitiligo Extent Score for a Target Area (VESTA)
      using reference images of both marginal and perifollicular repigmentation to
      measure the repigmentation rate (%) in a target lesion. In the validation study,
      a total of 65 dermatologists in 10 institutes evaluated 17 pairs of vitiligo
      images (pre- and post-treatment) using both a rough estimate and the VESTA. The
      VESTA (concordance correlation coefficient: 0.949, 95% confidence interval [CI]
      0.942-0.955) was significantly more accurate than the rough estimate (0.896, 95%
      CI: 0.883-0.908). It was also associated with better inter-rater reliability over
      the rough estimate, albeit not significant. The VESTA can afford intuitive,
      convenient, and reliable assessment of the treatment response in a target area,
      and would be useful in clinical practice as well as retrospective studies.

PMID- 30117288
TI  - Survival outcomes following primary tumor resection for patients with incurable
      metastatic colorectal carcinoma: Experience from a single institution.
AB  - OBJECTIVE: Palliative primary tumor resection (PTR) has been used for preventing
      and treating tumor-related complications. We aimed to determine whether PTR can
      increase overall survival (OS) in patients with unresectable metastatic
      colorectal cancer (CRC). METHODS: A retrospective review of a prospectively
      collected database in a single center was performed. Patients diagnosed with
      metastatic CRC from January 2004 to December 2014 were included. Patients who had
      attained curative resection or had disease recurrence were excluded. All patients
      were discussed at a multidisciplinary tumor board where subsequent treatment
      decisions were made. RESULTS: Altogether 408 patients were analyzed. Of these 145
      received PTR with palliative chemotherapy (PC; group A), 110 received PC only
      (group B), 52 received PTR only (group C), while 101 received neither PTR nor PC
      (group D). Undergoing PTR led to statistically significant improvement in OS
      (22.7 months vs 12.1 months vs 6.9 months vs 2.7 months, P < 0.001). We performed
      subgroup analyses to control for potential confounders and found that the
      influence of PTR on OS persisted. With multivariate analysis, the predictors of
      poor OS were no PTR (hazards ratio [HR] 2.32, 95% confidence interval [CI] 1.82
      2.96, P < 0.001), no PC (HR 4.25, 95% CI 3.27-5.33, P < 0.001) and the presence
      of peritoneal metastases (HR 1.37, 95% CI 1.06-1.78, P = 0.018). Diversion
      surgery did not lead to a statistical difference in OS. CONCLUSIONS: The absences
      of PTR and PC, and peritoneal metastases are independently associated with
      decreased OS in patients with unresectable metastatic CRC. Randomized controlled
      trials are needed to verify this observation.

PMID- 30117289
TI  - Characterization of the novel HLA-A*80:04 allele identified in a Spanish
      volunteer donor.
AB  - HLA-A*80:04 shows one amino acid replacement, A76 > E, when compared with the
      A*80:01 allele.

PMID- 30117291
TI  - New lncRNA annotation reveals extensive functional divergence of the
      transcriptome in maize.
AB  - Long non-coding RNAs (lncRNAs), whose sequences are approximately 200 bp or
      longer and unlikely to encode proteins, may play an important role in eukaryotic
      gene regulation. Although the latest maize (Zea mays L.) reference genome
      provides an essential genomic resource, genome-wide annotations of maize lncRNAs
      have not been updated. Here, we report on a large transcriptomic dataset
      collected from 749 RNA sequencing experiments across different tissues and stages
      of the maize reference inbred B73 line and 60 from its wild relative teosinte. We
      identified 18,165 high-confidence lncRNAs in maize, of which 6,873 are conserved
      between maize and teosinte. We uncovered distinct genomic characteristics of
      conserved lncRNAs, non-conserved lncRNAs, and protein-coding transcripts.
      Intriguingly, Shannon entropy analysis showed that conserved lncRNAs are likely
      to be expressed similarly to protein-coding transcripts. Co-expression network
      analysis revealed significant variation in the degree of co-expression.
      Furthermore, selection analysis indicated that conserved lncRNAs are more likely
      than non-conserved lncRNAs to be located in regions subject to recent selection,
      indicating evolutionary differentiation. Our results provide the latest genome
      wide annotation and analysis of maize lncRNAs and uncover potential functional
      divergence between protein-coding, conserved lncRNA, and non-conserved lncRNA
      genes, demonstrating the high complexity of the maize transcriptome.

PMID- 30117290
TI  - Desulfitobacterium contributes to the microbial transformation of 2,4,5-T by
      methanogenic enrichment cultures from a Vietnamese active landfill.
AB  - The herbicide 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) was a major component
      of Agent Orange, which was used as a defoliant in the Vietnam War. Little is
      known about its degradation under anoxic conditions. Established enrichment
      cultures using soil from an Agent Orange bioremediation plant in southern Vietnam
      with pyruvate as potential electron donor and carbon source were shown to degrade
      2,4,5-T via ether cleavage to 2,4,5-trichlorophenol (2,4,5-TCP), which was
      further dechlorinated to 3,4-dichlorophenol. Pyruvate was initially fermented to
      hydrogen, acetate and propionate. Hydrogen was then used as the direct electron
      donor for ether cleavage of 2,4,5-T and subsequent dechlorination of 2,4,5-TCP.
      16S rRNA gene amplicon sequencing indicated the presence of bacteria and archaea
      mainly belonging to the Firmicutes, Bacteroidetes, Spirochaetes, Chloroflexi and
      Euryarchaeota. Desulfitobacterium hafniense was identified as the dechlorinating
      bacterium. Metaproteomics of the enrichment culture indicated higher protein
      abundances of 60 protein groups in the presence of 2,4,5-T. A reductive
      dehalogenase related to RdhA3 of D. hafniense showed the highest fold change,
      supporting its function in reductive dehalogenation of 2,4,5-TCP. Despite an
      ether-cleaving enzyme not being detected, the inhibition of ether cleavage but
      not of dechlorination, by 2-bromoethane sulphonate, suggested that the two
      reactions are catalysed by different organisms.

PMID- 30117292
TI  - In vitro behavior and UV response of melanocytes derived from carriers of CDKN2A
      mutations and MC1R variants.
AB  - Coinheritance of germline mutation in cyclin-dependent kinase inhibitor 2A
      (CDKN2A) and loss-of-function (LOF) melanocortin 1 receptor (MC1R) variants is
      clinically associated with exaggerated risk for melanoma. To understand the
      combined impact of these mutations, we established and tested primary human
      melanocyte cultures from different CDKN2A mutation carriers, expressing either
      wild-type MC1R or MC1RLOF variant(s). These cultures expressed the CDKN2A product
      p16 (INK4A) and functional MC1R. Except for 32ins24 mutant melanocytes, the
      remaining cultures showed no detectable aberrations in proliferation or capacity
      for replicative senescence. Additionally, the latter cultures responded normally
      to ultraviolet radiation (UV) by cell cycle arrest, JNK, p38, and p53 activation,
      hydrogen peroxide generation, and repair of DNA photoproducts. We propose that
      malignant transformation of melanocytes expressing CDKN2A mutation and MC1RLOF
      allele(s) requires acquisition of somatic mutations facilitated by MC1R genotype
      or aberrant microenvironment due to CDKN2A mutation in keratinocytes and
      fibroblasts.

PMID- 30117293
TI  - Continuous intravenous infusion of insulin and heparin versus plasma exchange in
      hypertriglyceridemia-induced acute pancreatitis.
AB  - BACKGROUND: Acute triglyceride (TG) lowering therapy is crucial in the early
      treatment of hypertriglyceridemia (HTG)-induced pancreatitis. Data concerning
      continuous intravenous infusion of insulin and heparin therapy (IHT) as an
      equivalent option to plasma exchange (PE) in HTG-induced pancreatitis are
      limited. We performed this study to compare the IHT and PE abilities to lower TG
      levels in the acute phase of HTG-induced pancreatitis. METHODS: This was a
      retrospective observational study conducted in a tertiary teaching hospital.
      Patients with HTG-induced pancreatitis were consecutively enrolled from Oct 2013
      to Oct 2017. The primary outcome was the reduction in the TG level. RESULTS:
      Sixty-four patients were valid for assessment, 34 (53.1%) patients were included
      in the IHT group. A reduced TG level by 74.7+/-13.8% was observed after the first
      PE session, and a reduced TG level by 75.0+/-14.6% was observed after the 1st day
      of IHT. There were no significant differences in the reduction of TG (F=0.015,
      P>0.05), high-sensitivity C reactive protein (F=0.698, P>0.05) and the Acute
      Physiology and Chronic Health Evaluation II score (F=0.954, P>0.05) between the
      IHT group and the PE group. The cost of medical care in hospital was significant
      lower in the IHT group than the PE group (59512.4+/-23645.1 RMB vs 105483.9+/
      58815.4 RMB, P<0.05). No adverse effect was observed in the IHT group.
      CONCLUSIONS: As a minimally invasive and economical strategy, IHT is effective
      and equivalent to PE in achieving a fast reduction in TG levels. This article is
      protected by copyright. All rights reserved.

PMID- 30117294
TI  - Combinations of four or more CpGs methylation present equivalent predictive value
      for MGMT expression and temozolomide therapeutic prognosis in gliomas.
AB  - AIMS: The pyrosequencing (PSQ) has been regarded as the gold standard for MGMT
      promoter methylation testing in gliomas. However, various CpG combinations are
      currently used in clinical practice. We aimed to clarify how and how many CpGs
      combined is robust enough to predict MGMT mRNA expression and therapeutic
      prognosis of patients. METHODS: Total 223 patients with WHO III/IV gliomas were
      enrolled from Chinese Glioma Genome Atlas, including two independent cohorts, the
      eight-site cohort (with CpGs 75-82 tested) and the seven-site cohort (with CpGs
      72-78 tested). Spearman's correlation and ROC curves were employed to investigate
      the value of different CpG combinations on predicting MGMT mRNA expression. The
      ROC curves and Kaplan-Meier steps were performed to compare the TMZ therapeutic
      prognostic values of different CpG combinations. RESULTS: The methylation level
      of all individual CpG and CpG combinations for the eleven CpGs (CpGs 72-82),
      significantly correlated to MGMT mRNA expression (Spearman, all P < 0.0001),
      could effectively predict the mRNA expression (AUC, 0.86-0.91 in the eight-site
      cohort, 0.83-0.90 in the seven-site cohort). Moreover, the correlation
      coefficients and the predictive values presented equivalent when four or more
      CpGs combinedly used (AUC, 0.88-0.90 in the eight-site cohort, 0.87-0.88 in the
      seven-site cohort). Finally, similar results were also observed when using
      selected CpG combinations to predict therapeutic prognosis of patients.
      CONCLUSIONS: Four-CpG combinations of pyrosequencing are sufficient for
      evaluating the methylation status of MGMT and predicting therapeutic prognosis in
      gliomas.

PMID- 30117295
TI  - Postoperative bleeding after subtotal colectomy in two patients with severe
      ulcerative colitis.

PMID- 30117296
TI  - De novo UNC13B mutation identified in a bipolar disorder patient increases a rare
      exon-skipping variant.
AB  - AIM: We previously performed the first trio-based exome study for bipolar
      disorder and identified 71 de novo mutations. Among these mutations, the only
      mutation located at the splice donor site was in UNC13B. We focused on and
      analyzed the functions of the mutation. METHODS: In order to analyze the
      functional alterations, due to the mutation, we performed a minigene splicing
      assay. KEY RESULTS: We found that the mutation caused the loss of a wild-type
      splicing variant, which was consistent with the computational splice prediction,
      and that an exon-skipping variant increased significantly. The exon-skipping
      variant also existed in the wild-type minigene, although it was rare. Hence, we
      validated the expression of the exon-skipping variant using total RNAs derived
      from the human cerebral cortex. We showed the possibility that the exon-skipping
      variant was rare, but expressed even in those that do not carry the mutation.
      CONCLUSIONS: Based on our results, we suggest that an abnormal splicing pattern
      of UNC13B occurred in the patient, which could be related to the pathophysiology
      of bipolar disorder.

PMID- 30117297
TI  - Genomic characterization of Nocardia seriolae strains isolated from diseased
      fish.
AB  - Members of the genus Nocardia are widespread in diverse environments; a wide
      range of Nocardia species are known to cause nocardiosis in several animals,
      including cat, dog, fish, and humans. Of the pathogenic Nocardia species, N.
      seriolae is known to cause disease in cultured fish, resulting in major economic
      loss. We isolated two N. seriolae strains, CK-14008 and EM15050, from diseased
      fish and sequenced their genomes using the PacBio sequencing platform. To
      identify their genomic features, we compared their genomes with those of other
      Nocardia species. Phylogenetic analysis showed that N. seriolae shares a common
      ancestor with a putative human pathogenic Nocardia species. Moreover, N. seriolae
      strains were phylogenetically divided into four clusters according to host fish
      families. Through genome comparison, we observed that the putative pathogenic
      Nocardia strains had additional genes for iron acquisition. Dozens of antibiotic
      resistance genes were detected in the genomes of N. seriolae strains; most of the
      antibiotics were involved in the inhibition of the biosynthesis of proteins or
      cell walls. Our results demonstrated the virulence features and antibiotic
      resistance of fish pathogenic N. seriolae strains at the genomic level. These
      results may be useful to develop strategies for the prevention of fish
      nocardiosis.

PMID- 30117298
TI  - [Cp*RhIII ]/Ionic Liquid as a Highly Efficient and Recyclable Catalytic Medium
      for C-H Amidation.
AB  - A [Cp*RhIII ]-catalyzed direct C-H amidation is carried out in ionic liquid. Both
      C(sp2 )-H bonds of (hetero)arenes and alkenes and unactivated C(sp3 )-H bonds can
      be easily amidated with high functional-group tolerance and excellent yields
      under these conditions. Notably, using [Cp*RhIII ]/[BMIM]BF4 (BMIM=1-butyl-3
      methylimidazolium) as the green and recyclable medium is environmentally benign,
      in light of characteristics such as the reusability of the expensive rhodium
      catalyst, avoidance of highly toxic organic solvents, and mild reaction
      conditions, as well as a short reaction time.

PMID- 30117299
TI  - Effects of Astragalus membranaceus fiber on growth performance, nutrient
      digestibility, microbial composition, VFA production, gut pH, and immunity of
      weaned pigs.
AB  - Astragalus membranaceus is an herbaceous perennial plant, growing to about 2 feet
      tall, with sprawling stems and alternate leaves about 12-24 leaflets. In total,
      24 cross bred (Duroc * Landrace * Yorkshire) piglets weaned at 4 weeks with an
      average body weight of 10.84 +/- 1.86 kg, were divided into four groups and
      randomly assigned to dietary treatments containing different AMSLF levels (0.00%,
      2.50%, 5.00%, and 7.50%). The piglets in the control group (0.00% AMSLF) were fed
      basal diet and other treatment groups were fed basal diet in addition to 2.50%,
      5.00%, and 7.50% pulverized AMSLF. The results indicated that supplementation
      with AMSLF significantly (p < 0.05) decreased diarrheal incidence in piglets.
      There was significant difference between treatment in terms of ADFI, ADG and FCR.
      Both 5.00% and 7.50% treatments significantly increased growth performance. The
      digestibility of gross energy and dry matter increased (p > 0.05) with increasing
      AMSLF level. The level of blood IL-2 and TNF-alpha were significantly affected by
      AMSLF supplementation with 7.50% AMSLF group having higher (p < 0.05) IL-2 and
      TNF-alpha levels than the other treatment groups. The 16SrDNA sequencing results
      from the four treatments showed that the potentially active bacterial microbial
      population and diversity in pig cecum were dominated by the phyla Bacteriodetes
      and Firmicutes regardless of the AMSLF supplementation. The Shannon diversity, PD
      whole tree diversity indices and Chao analyses exhibited significant variability
      in species richness across the treatments. The principal coordinates analysis
      (PCoA) showed significant (p < 0.1) differences between bacterial communities in
      all treatment groups. Results from the current study suggested that AMSLF
      supplementation increased composition of bacterial microbiota in pig gut. In
      conclusion, dietary supplements with AMSLF could potentially be used to prevent
      diarrheal incidence and improved pig production.

PMID- 30117300
TI  - Evaluation of the Cardiac Safety of Long-Acting Endectocide Moxidectin in a
      Randomized Concentration-QT Study.
AB  - Potential effects on cardiac repolarization of single doses of moxidectin, a
      potent long-acting macrocyclic lactone endectocide, were assessed in a
      concentration-QT (c-QT; exposure-response) study. This double-blind, placebo
      controlled, parallel-group study in healthy male volunteers (n = 60) randomized
      subjects to a single oral dose of moxidectin (4 mg, 8 mg, 16 mg, 24 mg, or 36 mg)
      or matching placebo. Serial plasma samples for pharmacokinetic (PK) analysis and
      concurrent triplicate electrocardiogram measurements were taken at baseline and
      14 prespecified time points over 72 hours, yielding 900 QT interval-plasma
      concentration time-matched pairs. Moxidectin had no statistically significant or
      clinically relevant impact on QT interval at any dose level. The primary mixed
      effects model analysis revealed no treatment-related impact on the Fridericia
      corrected QT interval-plasma concentration gradient (-0.0077, 90% confidence
      interval (CI) -0.0255 to +0.0101).

PMID- 30117301
TI  - The HLA-C*07:478 allele identified in a volunteer donor for hematopoietic stem
      cell transplant.
AB  - HLA-C*07:478 differs from HLA-C*07:02:01:01 in codon 81 in exon 2.

PMID- 30117302
TI  - Fully coupled fluid-electro-mechanical model of the human heart for
      supercomputers.
AB  - In this work, we present a fully coupled fluid-electro-mechanical model of a 50th
      percentile human heart. The model is implemented on Alya, the BSC multi-physics
      parallel code, capable of running efficiently in supercomputers. Blood in the
      cardiac cavities is modeled by the incompressible Navier-Stokes equations and an
      arbitrary Lagrangian-Eulerian (ALE) scheme. Electrophysiology is modeled with a
      monodomain scheme and the O'Hara-Rudy cell model. Solid mechanics is modeled with
      a total Lagrangian formulation for discrete strains using the Holzapfel-Ogden
      cardiac tissue material model. The three problems are simultaneously and
      bidirectionally coupled through an electromechanical feedback and a fluid
      structure interaction scheme. In this paper, we present the scheme in detail and
      propose it as a computational cardiac workbench.

PMID- 30117303
TI  - Common and well-documented HLA alleles of German stem cell donors by haplotype
      frequency estimation.
AB  - We present a catalog of common and well-documented (CWD) alleles of the German
      population for the six HLA loci A, B, C, DRB1, DQB1, and DPB1. This study is
      based on a sample of over 5 million volunteer adult hematopoietic stem cell
      donors from the 26 German donor centers. To establish the catalog, allele and
      haplotype frequencies were estimated with a validated implementation of the
      expectation-maximization algorithm. CWD criteria similar to existing CWD catalogs
      were applied in order to be able to put our findings into the context of relevant
      existing references. Overall, 2155 HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 alleles
      were identified as CWD in the German donor population representing about 20% of
      the HLA alleles at two-field resolution in the IPD-IMGT/HLA Database release
      v3.25.0 from July 2016 for these six loci. We found a substantial concordance of
      CWD alleles between the three catalogs and showed the contribution of the German
      donor population to the CWD alleles domain. In conclusion, the definition of CWD
      criteria that allow interoperability, scalability, and flexibility will be
      crucial for the development of a worldwide CWD catalog.

PMID- 30117305
TI  - The HLA-C*01:32:02 allele identified in a volunteer donor for hematopoietic stem
      cell transplant.
AB  - HLA-C*01:32:02 differs from HLA-C*01:02:01:01 in codons 131 and 135 in exon 3.

PMID- 30117304
TI  - Molecular profiles of tumor contrast enhancement: A radiogenomic analysis in
      anaplastic gliomas.
AB  - The presence of contrast enhancement (CE) on magnetic resonance (MR) imaging is
      conventionally regarded as an indicator for tumor malignancy. However, the
      biological behaviors and molecular mechanism of enhanced tumor are not well
      illustrated. The aim of this study was to investigate the molecular profiles
      associated with anaplastic gliomas (AGs) presenting CE on postcontrast T1
      weighted MR imaging. In this retrospective database study, RNA sequencing and MR
      imaging data of 91 AGs from the Cancer Genome Atlas (TCGA) and 64 from the
      Chinese Glioma Genome Atlas (CGGA) were collected. Gene set enrichment analysis
      (GSEA), significant analysis of microarray, generalized linear models, and Least
      absolute shrinkage and selection operator algorithm were used to explore
      radiogenomic and prognostic signatures of AG patients. GSEA indicated that
      angiogenesis and epithelial-mesenchymal transition were significantly associated
      with post-CE. Genes driving immune system response, cell proliferation, and focal
      adhesions were also significantly enriched. Gene ontology of 237 differential
      genes indicated consistent results. A 48-gene signature for CE was identified in
      TCGA and validated in CGGA dataset (area under the curve = 0.9787). Furthermore,
      seven genes derived from the CE-specific signature could stratify AG patients
      into two subgroups based on overall survival time according to corresponding risk
      score. Comprehensive analysis of post-CE and genomic characteristics leads to a
      better understanding of radiology-pathology correlations. Our gene signature
      helps interpret the occurrence of radiological traits and predict clinical
      outcomes. Additionally, we found nine prognostic quantitative radiomic features
      of CE and investigated the underlying biological processes of them.

PMID- 30117306
TI  - Community composition of arbuscular mycorrhizal fungi associated with native
      plants growing in a petroleum-polluted soil of the Amazon region of Ecuador.
AB  - Arbuscular mycorrhizal fungi (AMF) are worldwide distributed plant symbionts.
      However, their occurrence in hydrocarbon-polluted environments is less
      investigated, although specific communities may be present with possible interest
      for remediation strategies. Here, we investigated the AMF community composition
      associated with the roots of diverse plant species naturally recolonizing a
      weathered crude oil pond in the Amazon region of Ecuador. Next generation 454 GS
      Junior sequencing of an 800 bp LSU rRNA gene PCR amplicon was used. PCR amplicons
      were affiliated to a maximum-likelihood phylogenetic tree computed from 1.5 kb
      AMF reference sequences. A high throughput phylogenetic annotation approach,
      using an evolutionary placement algorithm (EPA) allowed the characterization of
      sequences to the species level. Fifteen species were detected. Acaulospora
      species were identified as dominant colonizers, with 73% of relative read
      abundance, Archaeospora (19.6%) and several genera from the Glomeraceae
      (Rhizophagus, Glomus macrocarpum-like, Sclerocystis, Dominikia and Kamienskia)
      were also detected. Although, a diverse community belonging to Glomeraceae was
      revealed, they represented <10% of the relative abundance in the Pond. Seventy
      five % of the species could not be identified, suggesting possible new species
      associated with roots of plants under highly hydrocarbon-polluted conditions.

PMID- 30117307
TI  - The impact of liver resection on survival outcomes of hepatocellular carcinoma
      patients with extrahepatic metastases: A propensity score matching study.
AB  - BACKGROUND: The majority of hepatocellular carcinoma patients (HCCs) with
      extrahepatic metastases die of progressive intrahepatic tumor. There have been
      little data on the role of primary tumor resection (PTR) for HCCs with
      extrahepatic metastases but with resectable primary tumors. METHODS: A
      retrospective study was conducted on HCCs with extrahepatic metastases with
      resectable primary tumors who either underwent or did not undergo PTR in the SEER
      registry between 2004 and 2013. The overall and cancer-specific survivals (OS and
      CSS) were assessed by the log-rank test and the Cox proportional hazard
      regression model. A propensity score matching was conducted to minimize biases.
      Validation was performed in another cohort from the Sun Yat-sen Memorial Hospital
      (SYSMH). RESULTS: Of the 529 HCCs with extrahepatic metastases with resectable
      primary tumors included into this study, 230 patients underwent PTR and 299 did
      not. The percentages of patients who underwent PTR increased from 38.6% in 2004
      to 70.3% in 2013. In the propensity score-matched patients, PTR was associated
      with improved OS (HR 0.310, P < 0.001) and CSS (HR 0.326, P <0.001). These
      improvements in survivals remained significant after sensitivity analyses using
      multiple imputation. In the validation cohort from the SYSMH (n = 131), PTR was
      also correlated with improved OS (HR 0.508, P = 0.002) and CSS (HR 0.568, P =
      0.017). CONCLUSIONS: This study using propensity score matching and multiple
      imputation demonstrated that PTR had a favorable impact on the prognosis of HCCs
      with extrahepatic metastases with resectable primary tumors. Further prospective
      randomized trials are needed to confirm these findings.

PMID- 30117308
TI  - Relationship of BMI z score to fat percent and fat mass in multiethnic
      prepubertal children.
AB  - OBJECTIVE: The objective of the study is to examine the validity of body mass
      index z score (zBMI) as a measure of percent body fat in prepubertal children.
      METHODS: One hundred eleven multiethnic, healthy, Tanner 1 children aged 6-12
      years had fat percent and fat mass measured by the four-compartment method as
      part of the Paediatric Rosetta Body Composition Cohort. Multiple regression
      models were developed with fat percent as the dependent variable and zBMI, age,
      sex and ethnicity as independent variables. RESULTS: Body mass index z score
      predicted fat percent, adjusted for age in both girls (P < 0.001, RMSE 5.67 and
      R2 0.54) and boys (P < 0.001, RMSE 4.71, R2 0.69). The average model percent
      error was 20.3% in girls and 21.6% in boys. zBMI2 predicted fat mass when
      adjusted for age and zBMI in both girls (P < 0.001, RMSE 2.27 and R2 0.82) and
      boys (P < 0.001, RMSE 2.08 and R2 0.81). The average percent error was 7.2% in
      girls and 8.7% in boys. Age was associated with percentage body fat (P < 0.01),
      while ethnicity was not (P > 0.05). CONCLUSIONS: Given the relatively large error
      in the models, zBMI are not a useful indicator of fat mass in healthy, Tanner 1
      children. zBMI2 scores are associated with significantly lower absolute percent
      errors in girls and boys.

PMID- 30117309
TI  - An addiction model-based mobile health weight loss intervention in adolescents
      with obesity.
AB  - BACKGROUND: Clinical approaches to treating childhood obesity can be expensive
      and poorly reimbursed, and often produce suboptimal results. It has been
      theorized that overeating may have addictive qualities, and a sizable number of
      adolescents with obesity endorse addictive habits. Interestingly, few weight
      management interventions have tested techniques founded in addiction medicine
      principles. We therefore performed a pilot study of an addiction model based
      mHealth weight loss intervention in adolescents. METHODS: Adolescents with
      obesity were recruited from an multidisciplinary weight management clinic
      (EMPOWER). Adolescents without significant obesity comorbidities, who exhibited
      signs of addictive eating, based on the Yale Food Addiction Scale, were enrolled
      in a pilot study of an interactive, addiction-based, weight loss smartphone app
      with coaching (http://clinicaltrials.gov: NCT02689154). The app was designed to
      help subjects omit problem foods, avoid snacking and reduce meal size. A
      contemporary cohort of adolescents who completed the EMPOWER program were
      evaluated. Feasibility of recruitment, adherence, retention rates, BMI change and
      cost of intervention were examined. RESULTS: Eighteen participants were recruited
      to app intervention. App participants had higher retention (100% vs. 37%) and
      lower total cost per patient ($855.15 vs. $1428.00) than the EMPOWER clinic
      participants. App participants exhibited a significant decrease in zBMI and
      %BMIp95 over the 6 months (p < 0.001 and p = 0.001), which was comparable to the
      age-matched EMPOWER program completers (p = 0.31 and p = 0.06). CONCLUSIONS: An
      addiction medicine-based mHealth intervention targeted for adolescents was
      feasible to implement, resulted in high retention and adherence rates, and
      reduced zBMI and %BMIp95 in a more cost-effective manner than an in-clinic
      intervention.

PMID- 30117310
TI  - The HLA-C*06:66 allele identified in a volunteer donor for hematopoietic stem
      cell transplant.
AB  - HLA-C*06:66 differs from HLA-C*06:02:01:01 in codon 151 in exon 3.

PMID- 30117311
TI  - The HLA-C*03:272 allele identified in a volunteer donor for hematopoietic stem
      cell transplant.
AB  - HLA-C*03:272 differs from HLA-C*03:03:01:01 in exon 3, codon 163.

PMID- 30117314
TI  - Full gene HLA class I sequences of 79 novel and 519 mostly uncommon alleles from
      a large United States registry population.
AB  - HLA class I assignments were obtained at single genotype, G-level resolution from
      98 855 volunteers for an unrelated donor registry in the United States. In spite
      of the diverse ancestry of the volunteers, over 99% of the assignments at each
      locus are common. Within this population, 52 novel alleles differing in exons 2
      and 3 are identified and characterized. Previously reported alleles with
      incomplete sequences in the IPD-IMGT/HLA database (n = 519) were selected for
      full gene sequencing and, from this sampling, another 27 novel alleles are
      described.

PMID- 30117312
TI  - Effect of mechanistic target of rapamycin inhibitors on postrenal transplantation
      malignancy: A nationwide cohort study.
AB  - BACKGROUND: Post-transplantation malignancy influenced graft survival and overall
      survival in the patients receiving renal transplantation. Immunosuppressants
      influenced the immune surveillance, but whether immunosuppressive agents have
      impact for incidence of post-transplantation malignancy is still elusive in
      Taiwan. METHOD: We conducted a nationwide population-based study. Patients who
      did not have malignancy history and received kidney transplantation between 2000
      and 2010 were enrolled. Specific immunosuppressive users are defined as sustained
      use (more than 12 months) after renal transplantation. The primary outcome is the
      development of cancer after kidney transplantation. A Cox proportional hazards
      model was used to determine the risk of cancer development. RESULT: Among 4438
      recipients, 559 of them were diagnosed with malignancy after 1 year of
      transplantation. A total of 742 of recipients were as user of mechanistic target
      of rapamycin (mTOR) inhibitors. The mTOR users had higher rate of receiving pulse
      therapy. The hazard ratios (HR) for mTOR inhibitor users with exposure more than
      5 years for overall malignancy and urothelial malignancy were 0.68 (95% CI: 0.48
      0.95, P = 0.02) and 0.60 (95% CI: 0.36-0.99, P = 0.02), respectively. For the
      overall mortality and reentry of dialysis, the probability of both groups was
      similar (overall mortality: P = 0.53; reentry of dialysis: P = 0.77). CONCLUSION:
      Among the recipients of renal transplantation in Taiwan, mTOR inhibitors with
      exposure more than 5 years provided a protective role in reducing the risk of
      overall neoplasm and urothelial malignancy. The probability of reentry of
      dialysis and overall mortality was similar between the mTORi users and nonusers.

PMID- 30117313
TI  - Cancer patients as frequent attenders in emergency departments: A national cohort
      study.
AB  - BACKGROUND: Cancer patients contribute significantly to emergency department (ED)
      utilization. The objective of this study was to identify factors associated with
      patients becoming ED frequent attenders (FA) after a cancer-related
      hospitalization. METHODS: A retrospective cohort study was conducted using
      national administrative, billing, and death records of Singapore residents
      discharged alive from Singapore public hospitals from January 2012 to December
      2015, with a primary discharge diagnosis of cancer. Patients with four or more ED
      visits within any 12-month period after discharge from their index
      hospitalization were classified as FA. Time to FA distribution was estimated
      using the Kaplan-Meier method, and factors associated with risk of FA were
      identified using multivariate Cox regression analyses. RESULTS: Records for 47
      235 patients were analyzed, of whom 2980 patients were FA within the study
      period. Age (<17 years, hazard ratio [HR] 2.92, 95% CI 2.28-3.74; 75-84 years, HR
      1.29, 95% CI 1.16-1.45; and >=85 years, HR 1.71, 95% CI 1.45-2.02, relative to
      age 55-64), male gender (HR 1.26, 95% CI 1.16-1.37), Charlson comorbidity index
      (HR 1.21, 95% CI 1.19-1.23), and socioeconomic factors (Medifund use, HR 1.40,
      95% CI 1.23-1.59; housing subsidy type, HR 2.12, 95% CI 1.77-2.54) were
      associated with increased risk of FA. Primary malignancies associated with FA
      included brain and spine (HR 2.51, 95% CI 1.67-3.75), head and neck cancers
      (tongue, HR 2.05, 95% CI 1.27-3.31; hypopharynx, HR 2.72, 95% CI 1.56-4.74), lung
      (trachea and lung, HR 1.57, 95% CI 1.13-2.18; pleural, HR 3.69, 95% CI 2.12
      6.34), upper gastrointestinal (stomach, HR 1.93, 95% CI 1.26-2.74; esophagus, HR
      4.13, 95% CI 2.78-6.13), hepato-pancreato-biliary (liver, HR 1.42, 95% CI 1.01
      2.00, pancreas, HR 2.48, 95% CI 1.72-3.59), and certain hematological
      malignancies (diffuse non-Hodgkin's lymphoma, HR1.59, 95% CI 1.08-2.33, lymphoid
      leukemia, HR 1.86, 95% CI 1.21-2.86). Brain (HR 1.69, 95% CI 1.27-2.26), lung (HR
      1.31, 95% CI 1.01-1.71), liver (HR 1.46, 95% CI 1.14-1.89), and bone (HR 1.35,
      95% CI 1.04-1.76) metastases were also associated with FA. CONCLUSION: There are
      cancer-specific factors contributing to ED frequent attendance. Additional
      resources should be allocated to support high-risk groups and prevent unnecessary
      ED use.

PMID- 30117316
TI  - The new allele HLA-DRB1*14:54:01:04 in a Chinese family identified using next
      generation sequencing.
AB  - DRB1*14:54:01:04 has five nucleotide differences from DRB1*14:54:01:01 at 10544
      (G > A) and 9068 (TGAG insertion).

PMID- 30117315
TI  - Profiles of immune infiltration in colorectal cancer and their clinical
      significant: A gene expression-based study.
AB  - Immune infiltration of colorectal cancer (CRC) is closely associated with
      clinical outcome. However, previous work has not accounted for the diversity of
      functionally distinct cell types that make up the immune response. In this study,
      based on a deconvolution algorithm (known as CIBERSORT) and clinical annotated
      expression profiles, we comprehensively analyzed the tumor-infiltrating immune
      cells present in CRC for the first time. The fraction of 22 immune cells
      subpopulations was evaluated to determine the associations between each cell type
      and survival and response to chemotherapy. As a result, profiles of immune
      infiltration vary significantly between paired cancer and paracancerous tissue
      and the variation could characterize the individual differences. Of the cell
      subpopulations investigated, tumors lacking M1 macrophages or with an increased
      number of M2 macrophages, eosinophils, and neutrophils were associated with the
      poor prognosis. Unsupervised clustering analysis using immune cell proportions
      revealed five subgroups of tumors, largely defined by the balance between
      macrophages M1, M2, and NK resting cells, with distinct survival patterns, and
      associated with well-established molecular subtype. Collectively, our data
      suggest that subtle differences in the cellular composition of the immune
      infiltrate in CRC appear to exist, and these differences are likely to be
      important determinants of both prognosis and response to treatment.

PMID- 30117317
TI  - Organic Photo-Electrochemical Transistor-Based Biosensor: A Proof-of-Concept
      Study toward Highly Sensitive DNA Detection.
AB  - Organic bioelectronics have shown promising applications for various sensing
      purposes due to their significant advantages in term of high flexibility,
      portability, easy fabrication, and biocompatibility. Here, a new type of organic
      device, organic photo-electrochemical transistor (OPECT), is reported, which is
      the combination of an organic electrochemical transistor and a photo
      electrochemical gate electrode modified with CdS quantum dots (QDs). Thanks to
      the inherent amplification function of the transistor, the OPECT-based biosensor
      exhibits much higher sensitivity than that of a traditional biosensor. The
      sensing mechanism of the OPECT is attributed to the charge transfer between the
      photosensitive semiconductor CdS QDs and the gate electrode. In an OPECT-based
      DNA sensor, target DNA is labeled with Au nanoparticles (NPs) and captured on the
      gate electrode, which can influence the charge transfer on the gate caused by the
      exciton-plasmon interactions between CdS QDs and Au NPs. Consequently, a highly
      sensitive and selective DNA sensor with a detection limit of around 1 * 10-15 m
      is realized. It is expected that OPECTs can be developed as a high-performance
      platform for numerous biological detections in the future.

PMID- 30117319
TI  - Erratum: "A stepwise composite echocardiographic score predicts severe pulmonary
      hypertension in patients with interstitial lung disease" Simon Bax, Charlene
      Bredy, Aleksander Kempny, Konstantinos Dimopoulos, Anand Devaraj, Simon Walsh,
      Joseph Jacob, Arjun Nair, Maria Kokosi, Gregory Keir, Vasileios Kouranos, Peter
      M. George, Colm McCabe, Michael Wilde, Athol Wells, Wei Li, Stephen John Wort and
      Laura C. Price. ERJ Open Res 2018; 4: 00124-2017.
AB  - [This corrects the article DOI: 10.1183/23120541.00124-2017.].

PMID- 30117320
TI  - Supported Two-Dimensional Materials under Ion Irradiation: The Substrate Governs
      Defect Production.
AB  - Focused ion beams perfectly suit for patterning two-dimensional (2D) materials,
      but the optimization of irradiation parameters requires full microscopic
      understanding of defect production mechanisms. In contrast to freestanding 2D
      systems, the details of damage creation in supported 2D materials are not fully
      understood, whereas the majority of experiments have been carried out for 2D
      targets deposited on substrates. Here, we suggest a universal and computationally
      efficient scheme to model the irradiation of supported 2D materials, which
      combines analytical potential molecular dynamics with Monte Carlo simulations and
      makes it possible to independently assess the contributions to the damage from
      backscattered ions and atoms sputtered from the substrate. Using the scheme, we
      study the defect production in graphene and MoS2 sheets, which are the two most
      important and wide-spread 2D materials, deposited on a SiO2 substrate. For helium
      and neon ions with a wide range of initial ion energies including those used in a
      commercial helium ion microscope (HIM), we demonstrate that depending on the ion
      energy and mass, the defect production in 2D systems can be dominated by
      backscattered ions and sputtered substrate atoms rather than by the direct ion
      impacts and that the amount of damage in 2D materials heavily depends on whether
      a substrate is present or not. We also study the factors which limit the spatial
      resolution of the patterning process. Our results, which agree well with the
      available experimental data, provide not only insights into defect production but
      also quantitative information, which can be used for the minimization of damage
      during imaging in HIM or optimization of the patterning process.

PMID- 30117321
TI  - Internal Concentrations in Gammarids Reveal Increased Risk of Organic
      Micropollutants in Wastewater-Impacted Streams.
AB  - Internal concentrations link external exposure to the potential effect, as they
      reflect what the organisms actually take up and experience physiologically. In
      this study, we investigated whether frequently detected risk-driving substances
      in water were found in the exposed organisms and if they are classified the same
      based on the whole body internal concentrations. Field gammarids were collected
      upstream and downstream of ten wastewater treatment plants in mixed land use
      catchments. The sampling was conducted in autumn and winter, during low flow
      conditions when diffuse agricultural input was reduced. The field study was
      complemented with laboratory and flume experiments to determine the
      bioaccumulation potentials of selected substances. For 32 substances, apparent
      bioaccumulation factors in gammarids were determined for the first time. With a
      sensitive multiresidue method based on online-solid phase extraction followed by
      liquid chromatography coupled to high resolution mass spectrometry, we detected
      63 (semi-) polar organic substances in the field gammarids, showing higher
      concentrations downstream than upstream. Interestingly, neonicotinoids, which are
      particularly toxic toward invertebrates, were frequently detected and were
      further determined as major contributors to the toxic pressure based on the toxic
      unit approach integrating internal concentration and toxic potency. The total
      toxic pressure based on internal concentrations was substantially higher compared
      to when external concentrations were used. Thus, internal concentrations may add
      more value to the current environmental risk assessment that is typically based
      solely on external exposure.

PMID- 30117322
TI  - Three-Dimensional Atomistic Tomography of W-Based Alloyed Two-Dimensional
      Transition Metal Dichalcogenides.
AB  - Increased interest in two-dimensional (2D) materials and heterostructures for use
      as components of electrical devices has led to the use of an atomically mixed
      phase between semiconducting and metallic transition metal dichalcogenides that
      exhibited enhanced interfacial characteristics. To understand the lattice
      structure and properties of 2D materials on the atomic scale, diverse
      characterization methods such as Raman spectroscopy, high-resolution transmission
      electron microscopy (HR-TEM), and X-ray photoemission spectroscopy (XPS) have
      been applied. However, determination of the exact chemical distribution, which is
      a critical factor for the interfacial layer, was hindered by limitations of these
      typical methods. In this work, atom-probe tomography (APT) was introduced for the
      first time to analyze the three-dimensional atomic distribution and composition
      variation of the atomic-scale multilayered alloy structure W xNb(1- x)Se2.
      Composition profiles and theoretical calculations for each atom demonstrated the
      reaction kinetics and stoichiometric inhomogeneity of the W xNb(1- x)Se2 layer.
      The role of the intermediate layer was investigated by fabrication of a WSe2
      based field-effect transistor. Introduction of W xNb(1- x)Se2 between metallic
      NbSe2 and semiconducting WSe2 layers resulted in improved charge transport with
      lowering of the contact barrier.

PMID- 30117318
TI  - Core-binding factor acute myeloid leukemia with t(8;21): Risk factors and a novel
      scoring system (I-CBFit).
AB  - BACKGROUND: Although the prognosis of core-binding factor (CBF) acute myeloid
      leukemia (AML) is better than other subtypes of AML, 30% of patients still
      relapse and may require allogeneic hematopoietic cell transplantation (alloHCT).
      However, there is no validated widely accepted scoring system to predict patient
      subsets with higher risk of relapse. METHODS: Eleven centers in the US and Europe
      evaluated 247 patients with t(8;21)(q22;q22). RESULTS: Complete remission (CR)
      rate was high (92.7%), yet relapse occurred in 27.1% of patients. A total of
      24.7% of patients received alloHCT. The median disease-free (DFS) and overall
      (OS) survival were 20.8 and 31.2 months, respectively. Age, KIT D816V mutated
      (11.3%) or nontested (36.4%) compared with KIT D816V wild type (52.5%), high
      white blood cell counts (WBC), and pseudodiploidy compared with hyper- or
      hypodiploidy were included in a scoring system (named I-CBFit). DFS rate at 2
      years was 76% for patients with a low-risk I-CBFit score compared with 36% for
      those with a high-risk I-CBFit score (P < 0.0001). Low- vs high-risk OS at 2
      years was 89% vs 51% (P < 0.0001). CONCLUSIONS: I-CBFit composed of readily
      available risk factors can be useful to tailor the therapy of patients,
      especially for whom alloHCT is not need in CR1 (ie, patients with a low-risk I
      CBFit score).

PMID- 30117323
TI  - Cyclic Penta-Twinned Rhodium Nanobranches as Superior Catalysts for Ethanol
      Electro-oxidation.
AB  - Developing active and durable electro-catalysts toward ethanol oxidation reaction
      (EOR) with high selectivity toward the C-C bond cleavage is an important issue
      for the commercialization of direct ethanol fuel cell. Unfortunately, current
      ethanol oxidation electro-catalysts (e.g., Pt, Pd) still suffer from poor
      selectivity for direct oxidation of ethanol to CO2, and rapid activity
      degradation. Here we report a facile route to the synthesis of a new kind of
      cyclic penta-twinned (CPT) Rh nanostructures that are self-supported nanobranches
      (NBs) built with 1-dimension CPT nanorods as subunits. Structurally, the as
      prepared Rh NBs possess high percentage of open {100} facets with significant CPT
      induced lattice strains. With these unique structural characteristics, the as
      prepared CPT Rh NBs exhibit outstanding electrocatalytic performance toward EOR
      in alkaline solution. Most strikingly, the selectivity of complete conversion
      ethanol to CO2 on the CPT Rh NBs is measured to be as high as 14.5 +/- 1.1% at 
      0.15 V, far exceeding that for single-crystal tetrahedral nanocrystals,
      icosahedral nanocrystals, and commercial Rh black, as well as majority of
      reported values for Pt or Pd-based electro-catalysts. By combining with density
      functional theory calculation, the effects of different structural features of Rh
      on EOR are definitively elucidated. It was found that the large amount of open Rh
      (100) facets dominantly contribute to the outstanding activity and exceptionally
      high selectivity, while the additional tensile strain on (100) planes can further
      boost the catalytic activity by enhancing the adsorption strength and lowering
      the reaction barrier of dehydrogenation process of ethanol. As a proof of
      concept, the present work shows that rationally optimizing surface and electronic
      structure of electro-catalysts by simultaneously engineering their surface and
      bulk structures is a promising strategy to promote the performance of electro
      catalysts.

PMID- 30117324
TI  - Near Full-Length Genomic Characterization of HIV-1 CRF01_AE/B Recombinant Strains
      Identified in Hebei, China.
AB  - This study reports a novel HIV-1 recombinant form of CRF01_AE/B that was isolated
      from a 22-year-old male individual (HE150308) residing in Hebei province, China.
      The near full-length genome (NFLG) phylogenetic tree showed that the strain was
      clustered with CRF01_AE reference sequences and placed at the peripheral position
      within the branch of CRF01_AE strains. The bootscaning and similarity plot
      analysis revealed that the NFLG of this novel recombinant was composed of eight
      interlaced segments, including four CRF01_AE and four subtype B segments
      separated by seven breakpoints observed in the gag, pol, and nef regions of HIV-1
      genome. Phylogenetic analysis demonstrated that the CRF01_AE subregions were from
      the previously identified CRF01_AE cluster 5, and the B subregions were
      correlated with the B strains originated from Europe and America. They were all
      the lineages widely prevalent in men who have sex with men (MSM) population in
      China. In recent years, a large number of recombinants between CRF01_AE and B
      strains are constantly emerging in the MSM population in China. This continual
      and recurrent recombination between CRF01_AE and B in high-risk group people
      deserves more attention and further monitoring.

PMID- 30117325
TI  - Fetal death associated with the use of 3,4-MDPHP and alpha-PHP.
AB  - INTRODUCTION: The second largest group of new drugs monitored by the European
      Monitoring Centre for Drugs and Drug Addiction (EMCDDA) is synthetic cathinones.
      Substances that are controlled by the law are immediately replaced by new
      uncontrolled derivatives that cause constant and dynamic changes on the drug
      market. Some of the most recent synthetic cathinones that have appeared on the
      "legal highs" market are 3,4-methylenedioxy-alpha-pyrrolidinohexanophenone (3,4
      MDPHP) and alpha-pyrrolidinohexanophenone (alpha-PHP). CASE HISTORY: A 21-year
      old woman in the 36th week of pregnancy presented with psychomotor agitation.
      Fetal demise was demonstrated and a caesarean delivery performed. METHODS: The
      analyses were carried out by liquid chromatography with mass spectrometry (LC
      MS/MS). The analytes were isolated from the biological material by liquid-liquid
      extraction with n-butyl chloride. RESULTS: 3,4-MDPHP and alpha-PHP were detected
      and quantified in both the fetus' and the mothers blood, as well as in the
      mothers urine samples. The determined concentrations of 3,4-MDPHP and alpha-PHP
      were, 76 ng/mL and 12 ng/mL in the fetal blood sample, 16 ng/mL and traces in the
      mothers blood, and 697 mg/mL and 136 ng/mL in the mothers urine, respectively.
      DISCUSSION: The presented case demonstrates that 3,4-MDPHP and alpha-PHP
      transfers from maternal blood to fetal blood. Blood concentrations of these
      compounds were higher in the fetus than in the mother. Based on the known effects
      of these substances and the patient's presentation and clinical course, it would
      seem that these substances contributed to the fetal death. CONCLUSIONS: The
      detected substances transfer from maternal to fetal circulation, and synthetic
      cathinone blood concentration can be higher in the fetus than in the mother. This
      along with the fact immature metabolic ability makes a fetus more vulnerable to
      cathinones intoxication than adults.

PMID- 30117326
TI  - Functional Outcomes of Local Pedicle Graft Interpositional Arthroplasty in Adults
      With Severe Freiberg's Disease.
AB  - BACKGROUND:: Conservative treatment or debridement is generally sufficient for
      Freiberg's disease grades I and II but operative intervention for the late stages
      of the disease process (III-V) is more challenging. Debridement alone is not
      sufficient and various forms of arthroplasty have been put forward. We have
      evaluated the outcomes of patients treated with an interpositional arthroplasty
      technique using a pedicle graft of periosteum and fat made into a "Rollmop"
      spacer for severe Freiberg's disease. No results have previously been reported
      for this technique. METHODS:: Twenty-five consecutive cases (23 patients) were
      performed from February 2009 to September 2016 (20 females, 5 males). Mean age at
      surgery was 52.6 years (range 19-70.5 years) with 92% affecting the second
      metatarsal. Twenty-three were primary cases and 2 were revision cases. Five cases
      were stage III, 12 were stage IV, and 8 were stage V. All patients underwent
      interpositional arthroplasty using a periosteum and fat pedicle graft from the
      affected metatarsal shaft as described by Myerson. Patients were evaluated using
      Manchester-Oxford Foot Questionnaire (MOXFQ) and American Orthopaedic Foot &
      Ankle Society Questionnaire (AOFAS). Mean follow-up was 3.5 years (0.6-7.6
      years). Paired 2-tailed Student t tests were used to assess clinical
      significance. RESULTS:: Surgery allowed 8 patients to return to normal footwear,
      10 patients returned to fashion footwear/heels, and 5 returned to sports.
      Nineteen cases (17 patients) were assessed with patient-reported outcome measures
      and all showed a clinically and statistically significant improvement in their
      scores. Mean pre- and postoperative VAS pain scores were 6.2 (range 4-9) and 1.8
      (range 0-6) ( P < .05). Mean perioperative AOFAS scores were 45.6 (range 15-73)
      and 82.7 (range 57-100) ( P < .05). Mean perioperative MOXFQ scores were 60.0
      (range 23-89) and 18.1 (range 0-80) ( P < .05). CONCLUSION:: This novel
      interpositional arthroplasty technique using a "rollmop" of periosteum and fat
      for severe Freiberg's disease produced significant improvements in pain,
      functional outcome, and patient satisfaction without donor site morbidity.
      Furthermore, it allowed patients to return to desired footwear and sporting
      activities. The functional outcome and joint range of motion was superior after a
      K-wire was no longer placed across the joint, and we believe it is essential to
      avoid this to permit early range-of-motion exercises. LEVEL OF EVIDENCE:: Level
      IV, retrospective case series.

PMID- 30117327
TI  - Acceptance and Commitment Therapy for Trichotillomania: A Randomized Controlled
      Trial of Adults and Adolescents.
AB  - The purpose of this study was to examine acceptance and commitment therapy (ACT)
      as a standalone treatment for trichotillomania in a randomized controlled trial
      of adults and adolescents. Participants consisted of a community sample of
      treatment seeking adults and adolescents with trichotillomania. Of the eligible
      39 participants randomized into treatment and waitlist groups, 25 completed
      treatment and were included in the final analysis. Treatment consisted of a 10
      session ACT protocol. Multiple mixed models repeated measures analyses were
      utilized to evaluate changes in trichotillomania symptom severity, daily number
      of hairs pulled and urges experienced, and experiential avoidance from
      pretreatment to posttreatment. Findings indicated significant changes in symptom
      severity and daily hairs pulled, but not daily urges experienced or psychological
      flexibility. However, psychological flexibility saw a 24.5% decrease in the
      treatment group and reduced from clinical to subclinical levels on average. This
      study suggests that ACT alone is an effective treatment for adults and
      adolescents with trichotillomania. Outcomes appear to be similar to trials that
      combined ACT and habit reversal training (HRT).

PMID- 30117329
TI  - Efficacy, Acceptability, and Tolerability of Lisdexamfetamine, Mixed Amphetamine
      Salts, Methylphenidate, and Modafinil in the Treatment of Attention-Deficit
      Hyperactivity Disorder in Adults: A Systematic Review and Meta-analysis.
AB  - OBJECTIVE: Psychostimulants are the first-line treatment in adults with attention
      deficit hyperactivity disorder (ADHD). This meta-analysis aimed to evaluate the
      efficacy, acceptability, and tolerability of lisdexamfetamine (LDX), mixed
      amphetamine salts (MASs), modafinil (MDF), and methylphenidate (MPH) in
      comparison with placebo. DATA SOURCES: We systematically searched PubMed/MEDLINE
      and Clinicaltrials.gov in May 2016, along with CENTRAL and EU Clinical Trials
      Register in February 2016, for the randomized, double-blind, placebo-controlled,
      parallel-group clinical trials conducted on adults diagnosed with ADHD. STUDY
      SELECTION AND DATA EXTRACTION: Substantial comorbidity, substance abuse or
      dependence, and nonpharmacological interventions represented grounds for
      exclusion. Published reports were the sole source for data extraction.
      Improvement in ADHD symptoms was the primary outcome. Random-effects model meta
      analysis was applied to calculate the standardized mean difference (SMD) with 95%
      CIs. DATA SYNTHESIS: The search retrieved 701 records, of which 20 studies were
      eligible for analysis. High effect size (expressed as SMD) in reducing ADHD
      symptoms was observed for LDX (-0.89; 95% CI = -1.09, -0.70), whereas MASs (
      0.64; 95% CI = -0.83, -0.45) and MPH (-0.50; 95% CI = -0.58, -0.41) reduced
      symptoms moderately compared with placebo. No efficacy was shown for MDF (0.08;
      95% CI; -0.18, 0.34). Relevance to Patient Care and Clinical Practice: In this
      meta-analysis, the efficacy, tolerability, and acceptability of psychostimulants
      were compared with that for placebo. Five of the included trials have not been
      evaluated in any of the previously published meta-analyses. CONCLUSIONS: The
      results suggest that LDX has the largest effect size and has a promising
      potential for treating adults with ADHD.

PMID- 30117330
TI  - Hypepontine, a new quaternary alkaloid with antimicrobial properties.
AB  - New isoquinoline alkaloid hypepontine (1) together with a five known compounds,
      were identified in Hypecoum ponticum Velen, the partial synonym of Hypecoum
      procumbens L. The structure of the new substance was elucidated based on
      spectroscopic evidence. The tertiary and quaternary alkaloid mixtures as well as
      the isolated alkaloids were evaluated for their antibacterial and antifungal
      activity. The result revealed that the crude alkaloid mixture containing
      quaternary isoquinoline alkaloids showed potent antifungal and antibacterial
      activity.

PMID- 30117331
TI  - Advances in Gene Therapy for Fanconi Anemia.
AB  - Fanconi anemia (FA) is a rare inherited disease that is associated with bone
      marrow failure and a predisposition to cancer. Previous clinical trials
      emphasized the difficulties that accompany the use of gene therapy to treat bone
      marrow failure in patients with FA. Nevertheless, the discovery of new drugs that
      can efficiently mobilize hematopoietic stem cells (HSCs) and the development of
      optimized procedures for transducing HSCs, using safe, integrative vectors,
      markedly improved the efficiency by which the phenotype of hematopoietic
      repopulating cells from patients with FA can be corrected. In addition, these
      achievements allowed the demonstration of the in vivo proliferation advantage of
      gene-corrected FA repopulating cells in immunodeficient mice. Significantly, new
      gene therapy trials are currently ongoing to investigate the progressive
      restoration of hematopoiesis in patients with FA by gene-corrected autologous
      HSCs. Further experimental studies are focused on the ex vivo transduction of
      unpurified FA HSCs, using new pseudotyped vectors that have HSC tropism. Because
      of the resistance of some of these vectors to serum complement, new strategies
      for in vivo gene therapy for FA HSCs are in development. Finally, because of the
      rapid advancements in gene-editing techniques, correction of CD34+ cells isolated
      from patients with FA is now feasible, using gene-targeting strategies. Taken
      together, these advances indicate that gene therapy can soon be used as an
      efficient and safe alternative for the hematopoietic treatment of patients with
      FA.

PMID- 30117332
TI  - "Ghost tablet" husks excreted in feces in large bupropion XL overdose.
AB  - BACKGROUND: Extended-release medications are widely prescribed across the
      spectrum of medical specialties; however, there is heterogeneity in how they are
      formulated. Commonly, they consist of an insoluble matrix or shell from which
      drug elutes, which may then be observed by patients when excreted in feces. We
      describe the case of a patient who ingested a large amount of extended-release
      bupropion tablets and subsequently passed a large number of these so-called
      "ghost tablets" in his stool. CASE DETAILS: A 19-year-old male presented in
      status epilepticus following intentional overdose of an unknown substance. He had
      prolonged QRS and QT intervals on ECG, hypotension requiring vasopressors, and
      tachycardia, and progressed to cardiac arrest and respiratory failure. On
      hospital day 4, he passed several large bowel movements containing apparent
      tablets. Serum bupropion and hydroxybupropion levels performed on serum taken at
      time of admission were 1800 ng/mL and 4200 ng/mL, respectively. Case Discussion:
      "Ghost tablets," the insoluble remnant of some extended-release dosage forms,
      have been previously reported to appear in patients' stool in the course of
      therapeutic dosing. We present the case of a considerable quantity of these ghost
      tablets recovered from stool following a large bupropion XL overdose. CONCLUSION:
      Healthcare providers should be aware of the potential for this phenomenon to
      occur in poisoned patients. It should be documented as physical evidence of
      overdose in addition to clinical evidence.

PMID- 30117333
TI  - Development and validation of an ELISA with high sensitivity for therapeutic
      monitoring of afatinib.
AB  - AIM: To support the therapeutic drug monitoring of afatinib (AFT), an ELISA was
      required. RESULTS: A hapten for AFT was prepared and linked to each of BSA and
      KLH proteins by diazotization/coupling reaction. A polyclonal antibody
      recognizing AFT with high affinity (IC50 = 40 ng ml-1) was generated and used in
      the development of a competitive ELISA for quantitation of AFT in plasma samples.
      The assay limit of detection was 2 ng ml-1. The assay accuracy and precision were
      proved. CONCLUSION: The assay is an appropriate alternative to the existing LC
      MS/MS assays for AFT and it is anticipated to effectively contribute to the
      therapeutic drug monitoring of AFT in clinical settings.

PMID- 30117334
TI  - Aflibercept plus FOLFIRI in Asian patients with pretreated metastatic colorectal
      cancer: a randomized Phase III study.
AB  - AIM: To investigate whether the benefit of combining aflibercept with 5
      fluorouracil, folinic acid and irinotecan (FOLFIRI) chemotherapy could be
      confirmed in patients from the Asia-Pacific region (ClinicalTrials.gov:
      NCT01661270). Patients & methods: Asian patients with oxaliplatin-pretreated
      metastatic colorectal cancer were randomized to receive aflibercept or placebo,
      followed by FOLFIRI. The primary end point was progression-free survival.
      RESULTS: The intention-to-treat population comprised 332 patients. A clinical
      supply misallocation resulted in 198/332 (60%) patients receiving at least one
      cycle of misallocated treatment. Nevertheless, the addition of aflibercept to
      FOLFIRI was shown to improve progression-free survival (hazard ratio: 0.629; 95%
      CI: 0.488-0.812). Adverse events were in line with expectations. CONCLUSION: The
      beneficial treatment effect associated with the addition of aflibercept to
      FOLFIRI was confirmed in Asian patients with pretreated metastatic colorectal
      cancer.

PMID- 30117337
TI  - Identification of Two Novel HIV-1 Second-Generation Recombinant Forms
      (CRF01_AE/07_BC) in Shaanxi, China.
AB  - Sexual contact is the main route of transmission of HIV type 1 (HIV-1) pandemic
      in China. New unique recombinant forms (URFs) were increasingly characterized in
      sexual populations in recent years. We reported two URFs identified from two male
      HIV-1-positive patients who were infected through sexual exposure in Shaanxi,
      China. Phylogenetic analyses and bootscan analyses revealed that the near full
      length genomes of the two URFs were having four recombinant breakpoints, with two
      CRF07_BC fragments inserted into CRF01_AE backbones. The CRF01_AE fragments of
      the two URFs clustered with previously reported a cluster 5 lineage of CRF01_AE.
      The four recombinant breakpoints of the two URFs were quite similar. The
      emergence of the new CRF01_AE/07_BC URFs indicated the complexity genetic
      variability and the active epidemic of HIV-1. Much more attention should be paid
      to monitor the emergency of recombinant strains.

PMID- 30117335
TI  - Mesial Temporal Sclerosis in SCN1A-Related Epilepsy: Two Long-Term EEG Case
      Studies.
AB  - Patients with temporal lobe epilepsy (TLE) due to mesial temporal sclerosis (MTS)
      are eligible candidates for resective epilepsy surgery. We report on 2 male
      patients aged 4 years with suspected TLE due to MTS who were referred for
      presurgical evaluation. Both patients came to medical attention within the first
      year of life suffering from febrile status epileptici and subsequent unprovoked
      seizures. The following years, moderate developmental delay was present. High
      resolution magnetic resonance imaging confirmed hippocampal sclerosis. Continuous
      EEG video monitoring revealed seizure patterns contralateral to the MTS in both
      patients. Genetic analysis was performed as both the clinical presentation of the
      patients and EEG video monitoring findings were not consistent with the presence
      of the hippocampal sclerosis alone and revealed de novo mutations within exon of
      the SCN1A gene. Resective surgical strategies were omitted due to the genetic
      findings. In conclusion, both patients suffered from a dual pathology syndrome
      with ( a) TLE related to MTS resulting most likely from recurrent febrile status
      in early childhood and ( b) Dravet syndrome, which is most likely the cause of
      the febrile convulsions leading to the MTS in these 2 patients.

PMID- 30117338
TI  - Examining the impact of a city-wide intensive interaction staff training program
      for adults with profound and multiple learning disability: a mixed methods
      evaluation.
AB  - PURPOSE: Intensive interaction is used to increase communication in people at a
      pre-verbal stage of communication development. The aim of the study was to
      evaluate a city-wide implementation of intensive interaction training to care
      staff by investigating how staff use intensive interaction with adults with
      profound and multiple learning disability, and their perceived impact of
      intensive interaction on these service users. METHOD: In phase 1, a survey
      investigated the outcomes of intensive interaction training on the work practices
      of staff supporting people with profound and multiple learning disability. In
      phase 2, individual interviews were conducted with staff to further investigate
      these experiences and perceptions. Interviews were analyzed using thematic
      analysis. RESULTS: Almost all of the participants (96%) reported using intensive
      interaction at work with 76% wanting to use intensive interaction with more
      people. Factors preventing staff from using Intensive Interaction were
      highlighted. Three over-arching themes were identified from the interviews; the
      impact of Intensive Interaction; facilitating the implementation of Intensive
      Interaction and; the organizational support and barriers to the implementation of
      Intensive Interaction. CONCLUSIONS: Training in intensive interaction at a city
      wide level enables staff to develop their knowledge of the approach and to engage
      in intensive interaction to promote the social inclusion of adults with profound
      and multiple learning disability. The barriers preventing staff from engaging in
      Intensive Interaction with adults with profound and multiple learning disability
      should be addressed. Implications for Rehabilitation Training care staff in
      intensive interaction promotes social inclusion for adults with profound and
      multiple learning disability. Care staff are able to identify changes in the
      interactive and communicative behaviors of adults with profound and multiple
      learning disability. Care staff perceive they are able to facilitate changes in
      the interactive and communicative behaviors of adults with profound and multiple
      learning disability. Care staff need continued support and training to sustain
      their use of Intensive Interaction with adults with profound and multiple
      learning disability. Services need to reduce the barriers of staffing, management
      and organizational structure to enable care staff to sustain their use of
      Intensive Interaction for adults with profound and multiple learning disability.

PMID- 30117340
TI  - Are Self-Efficacy and Weight Perception Associated With Physical Activity and
      Sedentary Behavior in Hispanic Adolescents?
AB  - Little is known about the correlates of physical activity and sedentary behavior
      in Hispanic adolescents. This study examined at baseline and 2-year follow-up:
      (1) the relationship between self-efficacy for physical activity and physical
      activity, (2) the association of weight perception with physical activity and
      sedentary behavior, and (3) whether sex moderated these associations. Hispanic
      adolescents ( N = 483 at baseline; age 15-17 years; 55.1% girls) completed
      questionnaires that assessed their self-efficacy for physical activity, weight
      perception, and time spent in physical activity and sedentary behavior. Multiple
      group path analyses were conducted to examine the proposed relationships and
      determine whether they were moderated by sex. Models controlled for body mass
      index, weight loss intention, participation on a sports team, language spoken at
      home, parental education, and country of birth. Self-efficacy was related to time
      spent in physical activity in boys ( b = .35, p < .001) and girls ( b = .41, p <
      .001) at baseline, but not 2 years later. No association was found for weight
      perception and time spent in physical activity and sedentary behavior. Post hoc
      analyses for overweight participants at baseline showed that weight perception
      was associated with time spent watching television. Overall, the findings suggest
      that self-efficacy is an important correlate, but not a predictor, of physical
      activity among Hispanic adolescents. Including strategies to address and enhance
      self-efficacy for physical activity in lifestyle interventions may increase
      adherence to physical activity recommendations and help reduce the high
      prevalence of obesity in this population.

PMID- 30117341
TI  - Framing Obesity: Effects of Obesity Labeling and Prevalence Statistics on Public
      Perceptions.
AB  - The rising prevalence rate of obesity in the United States has accentuated
      concerns about obesity-related problems as a major public health issue, which has
      motivated widespread efforts to increase public knowledge and to motivate
      individuals to change their relevant behaviors. Although health campaign messages
      commonly include information about prevalence rates for obesity, the impact of
      obesity labeling and prevalence rate descriptions in such messages has been
      overlooked by researchers. This online framing experiment fills the research gap
      by investigating the effects of obesity labeling (disease vs. body type) and
      prevalence statistics (prevalence rates of obesity, extreme obesity, combined
      overweight-obesity, or no prevalence information). Our findings suggest that
      obesity perceptions deviate from reality and that participants use framed cues in
      the health message as reference points when making judgments related to the
      nature and prevalence of obesity. Moreover, this study shows that even accurate
      information might lead to inaccurate perceptions as a result of framing, and
      perceptions of the nature and prevalence of obesity mediate the effects of
      framing on behavioral intentions. Implications for obesity framing and the design
      of public health messages are discussed.

PMID- 30117342
TI  - Ripple Effects of the Communities Preventing Childhood Obesity Project.
AB  - This research examines the practice of community coaching within coalitions in
      the Communities Preventing Childhood Obesity project. A quasi-experimental design
      was used in seven Midwestern states. Each state selected two rural, low-income
      communities with functioning health coalitions. Coalitions were randomly assigned
      to be intervention or comparison communities. After 4 years of the coaching
      intervention, ripple effect mapping served as one method for examining the
      coalitions' work that may affect children's weight status. A research team from
      each state conducted ripple effect mapping with their two coalitions, resulting
      in 14 ripple maps. Community capitals framework and the social-ecological model
      were used for coding the items identified within the ripple maps. A quantitative
      scoring analysis determined if differences existed between the intervention and
      comparison coalitions in terms of the activities, programs, funding, and
      partnerships for social-ecological model score (e.g., individual, community,
      policy levels), community capitals score, and ripples score (e.g., number of
      branches formed within the maps). All scores were higher in intervention
      communities; however, the differences were not statistically significant ( p >
      .05). Assessing community assets, such as availability of a community coach, is
      necessary in order to decide whether to deploy certain resources when designing
      health promotion strategies.

PMID- 30117344
TI  - Association Between Pre-season Training and Performance in Elite Australian
      Football.
AB  - PURPOSE: To examine the association between pre-season training variables and
      subsequent in-season performance in an elite Australian football team. METHODS:
      Data from forty-one elite male Australian footballers (mean+/-SD: age=23.4+/
      3.1y; height=188.4+/-7.1cm; mass=86.7+/-7.9kg) was collected from one Australian
      Football League (AFL) club. Pre-season training data (external load, internal
      load, fitness testing and session participation) were collected across the 17
      week pre-season phase (6-weeks pre-Christmas, 11-weeks post-Christmas). Champion
      Data(c) Player Rank (CDPR), coaches' ratings (CR) and round one selection were
      used as in-season performance measures. CDPR and CR were examined over the entire
      season, first half of the season and the first four games. Both Pearson and
      partial (controlling for AFL age) correlations were calculated to assess if any
      associations existed between pre-season training variables and in-season
      performance measures. A median-split was also employed to differentiate between
      higher and lower performing players for each performance measure. RESULTS: Pre
      season training activities appeared to have almost no association with
      performance measured across the entire season and the first half of the season.
      However, many pre-season training variables were significantly linked with
      performance measured across the first four games. Pre-season training variables
      that were measured post-Christmas were the most strongly associated with in
      season performance measures. Specifically, Total on-field session rating of
      perceived exertion (sRPE) post-Xmas, a measurement of internal load, displayed
      the greatest association with performance. CONCLUSIONS: Late pre-season training
      (especially on-field match specific training) is associated with better
      performance in the early season.

PMID- 30117343
TI  - Clinical Benefits of Acupuncture for the Reduction of Hormone Therapy-Related
      Side Effects in Breast Cancer Patients: A Systematic Review.
AB  - IMPORTANCE: Acupuncture can help reduce unpleasant side effects associated with
      endocrine therapy for breast cancer. Nevertheless, comprehensive evaluation of
      current evidence from randomized controlled trials(RCTs) is lacking. OBJECTIVE:
      To estimate the efficacy of acupuncture for the reduction of hormone therapy
      related side effects in breast cancer patients. EVIDENCE REVIEW: RCTs of
      acupuncture in breast cancer patients that examined reductions in hormone therapy
      related side effects were retrieved from PubMed, EMBASE, Web of Science, Ovid
      MEDLINE, and Cochrane Library databases through April 2016. The quality of the
      included studies was evaluated according to the 5.2 Cochrane Handbook standards,
      and CONSORT and STRICTA (Revised Standards for Reporting Interventions in
      Clinical Trials of Acupuncture) statements. INTERVENTION: Interventions included
      conventional acupuncture treatment compared with no treatment, placebo, or
      conventional pharmaceutical medication. Major outcome measures were the
      alleviation of frequency and symptoms and the presence of hormone therapy-related
      side effects. Findings/Results. A total of 17 RCTs, including a total of 810
      breast cancer patients were examined. The methodological quality of the trials
      was relatively rigorous in terms of randomization, blinding, and sources of bias.
      Compared with control therapies, the pooled results suggested that acupuncture
      had moderate effects in improving stiffness. No significant differences were
      observed in hot flashes, fatigue, pain, gastrointestinal symptoms, Kupperman
      index, general well-being, physical well-being, tumor necrosis factor (TNF), and
      interleukin (IL). CONCLUSIONS: Acupuncture therapy appears to be potentially
      useful in relieving functional stiffness. However, further large-sample trials
      with evidence-based design are still needed to confirm these findings.

PMID- 30117345
TI  - How do Physical Activity and Health Vary Among Younger, Middle-Aged and Older
      Adults With and Without Disability?
AB  - Physical activity (PA) and health were compared in younger (YA; 18-44 years),
      middle-aged (MA; 45-64 years), and older (OA; >65 years) adults with disability
      (PWD), functional limitation (PFL), or without disability (PWoD). Disability
      occurred in YA (PWD: 2.3%; PFL: 14.3%), MA (PWD: 8.5%; PFL: 23.8%), and OA (PWD:
      14.9%; PFL: 26.6%). Not meeting aerobic/muscle strengthening (MS) PA
      recommendations was frequent in YA (PWD: 50.7%, PFL: 42.5%; PWoD: 35.8%), MA
      (PWD: 56.7%; PFL: 44.0%; PWoD: 35.6%), and OA (PWD: 57.8%; PFL: 44.1%; PWoD:
      33.1%). Among PWD, YA and MA met MS more frequently than OA; PFL did more aerobic
      PA than PWD. Presence of more chronic diseases, female gender, White race, lower
      education, and less income was associated with being PWD and/or PFL. Those with
      greater PA were less likely to be PWD or PFL. Results suggest increasing public
      health efforts to promote healthy lifestyles in MA and OA.

PMID- 30117346
TI  - Maintaining an Effective Circle: Volunteer Experiences of Operational Aspects of
      Circles of Support and Accountability.
AB  - In Circles of Support and Accountability (CoSA), trained volunteers support an
      individual convicted for sexual offenses to reintegrate safely into the
      community. Developed in Canada, CoSA has been established in many jurisdictions
      with a growing number of volunteers; however, little is known about whether the
      training and support provided meets volunteer needs. Using a mixed-methods
      approach, the aim of the present research was to explore New Zealand CoSA
      volunteer experiences of the training and support they received and their
      perceptions about what contributed to the effective operation of a circle. In
      total, 18 volunteers took part in an interview and 23 volunteers completed a
      questionnaire. The findings found a mixed response to the training and support
      received, whereby some volunteers thought the training and support was adequate,
      whereas other felt the training support they received was inadequate. Findings
      also illustrate that adequate training, having access to a circle coordinator,
      selecting the right volunteers and core member, clear communication, and setting
      up boundaries were important factors in maintaining an effective circle. Findings
      are discussed in terms of implications for the training and support offered to
      current and future volunteers, as well as for maintaining the effectiveness of
      future circles.

PMID- 30117347
TI  - Hip, Knee, and Ankle Functional Demand During Habitual and Fast-Pace Walking in
      Younger and Older Women.
AB  - This study compared functional demand (FD) between older and younger women
      walking at habitual and fast speed and determined strength thresholds necessary
      to maintain FD below 80%. FD was calculated by expressing walking flexion and
      extension joint torques of the ankle, knee, and hip as a percentage of maximal
      strength. Young women had an average FD of 65% across joint actions and speeds,
      whereas older women had FD of 90%. In older women, the greatest FD occurred in
      the hip musculature. The hip, knee, and ankle extensor strengths required to
      maintain FD below 80% were 1.66, 1.86, and 0.57 Nm/kg, and flexor strengths were
      1.24, 0.49, and 0.69 Nm/kg, respectively. Older women have limited functional
      reserve to increase gait speed and rely heavily on available hip strength during
      walking. This study identifies strength targets for the hip, knee, and ankle that
      will assist in maintaining FD of older women at a sustainable level.

PMID- 30117348
TI  - Extracorporeal membrane oxygenation in trauma: A single institution experience
      and review of the literature.
AB  - INTRODUCTION:: Limited options exist for cardiovascular support of the trauma
      patient in extremis. This patient population offers challenges that are often
      considered insurmountable. This article identifies a heterogeneous group of
      trauma patients in extremis who may benefit from extracorporeal membrane
      oxygenation. METHODS:: Data were sourced from the medical records of all patients
      placed on extracorporeal membrane oxygenation following trauma at a Level I
      Trauma Center between 1 December 2016 and 1 December 2017. RESULTS:: All patients
      were male (N = 7), mostly with blunt injuries (n = 5), with an average age of 41
      years and with an average Injury Severity Scores of 33 (median = 34). Two out of
      seven patients survived (28.5%). Survivors tended to have a longer duration on
      extracorporeal membrane oxygenation (13.5 vs 3.8 days), had extracorporeal
      membrane oxygenation initiated later (15 vs 7.8 days), and had suffered a blunt
      injury. Two patients were initiated on veno-arterial extracorporeal membrane
      oxygenation (both non-survivors) and five were initiated on veno-venous
      extracorporeal membrane oxygenation (two survivors, three non-survivors). Five
      patients were heparinized immediately (one survivor, four non-survivors), and two
      patients were heparinized after clotting was noted in the circuit (one survivor,
      one non-survivor). Three of the seven (42.8%) patients suffered cardiac arrest
      either prior to, or during, the initiation of extracorporeal membrane oxygenation
      (all non-survivors). DISCUSSION:: Extracorporeal membrane oxygenation use in the
      trauma patient in extremis is not standard; however, this article demonstrates
      that extracorporeal membrane oxygenation is feasible in a complex, heterogeneous
      patient population when treated at designated centers.

PMID- 30117349
TI  - Associations Between Physical Function and Subjective Well-Being in Older Adults
      From Low- and Middle-Income Countries: Results From the Study on Global AGEing
      and Adult Health (SAGE).
AB  - BACKGROUND: Physical function is positively associated with subjective well-being
      in older adults from high-income nations. This study tests whether this
      association is evident in low- and middle-income countries. METHODS: Data were
      drawn from the study on global AGEing and adult health, using nationally
      representative samples of individuals over 50 years old from China, Ghana, India,
      Mexico, Russia, and South Africa. Participant interviews measured well-being
      (quality of life, mood, and happiness) and physical function (grip strength,
      usual and rapid gait speed). Logistic regressions tested relations between
      physical function and well-being variables within each country. RESULTS: Higher
      physical function measures exhibited moderate, yet significant, associations with
      increased odds of highly rated well-being (p < .05). However, higher gait speeds
      were unexpectedly associated with decreased odds of highly rated well-being (p <
      .05) in South Africa and Russia. CONCLUSION: These results suggest that physical
      function is generally positively associated with perceived well-being in older
      individuals from lower income nations.

PMID- 30117350
TI  - The inhibition of first-pass metabolism of ethanol by H2-receptor antagonists: a
      tabulated review.
AB  - INTRODUCTION: In the 1980s-1990s numerous studies were performed on H2-receptor
      antagonist inhibition of ethanol first-pass metabolism. Blood alcohol
      concentrations warranting possible driving under the influence citations in the
      United States have subsequently dropped from >=100 mg/dL to 50 mg/dL (Utah in
      2019) (30 mg/dL or zero tolerance in some parts of the world). A reexamination of
      these studies seemed important. Areas covered: Papers were compiled that
      addressed the effect of cimetidine, ranitidine, famotidine, and nizatidine on
      ethanol metabolism first from a PubMed search and then from citations within
      these papers. Studies were tabulated for fasting versus fed, ethanol and H2
      receptor antagonist dose and a summary of pharmacokinetic changes. Expert
      opinion: At doses of 0.15-0.30 mg/kg in the postprandial state (primarily after
      breakfast), the H2-receptor antagonists: cimetidine, ranitidine, famotidine, and
      nizatidine have all been found to increase the first-pass metabolism of ethanol.
      With cimetidine, there were sufficient studies to suggest it might be inhibitory
      outside these restricted states. While the role of inhibition of alcohol
      dehydrogenase has not been clearly defined, there is circumstantial evidence to
      support this mechanism. Further studies are required to elucidate the ability of
      H2-receptor antagonists to inhibit first-pass metabolism of ethanol.

PMID- 30117351
TI  - Organizational Directors' Perceptions About Awareness of Services Among Their
      Employees and the Older Adults They Serve.
AB  - OBJECTIVES: This study explores the extent to which directors of organizations
      perceive that (a) older adults are aware of and interested in using services, and
      (b) their employees are aware of complementary services in the community and are
      willing to coordinate care or refer older adults to these services. METHOD: We
      conducted 41 qualitative semistructured interviews with organizational directors
      who provide services to older adults. RESULTS: Directors perceived that not only
      older adults but also some providers were unaware of services in the community.
      Directors reported that some older adults felt stigmatized and were unwilling to
      use services, but services providers implemented strategies to overcome these
      barriers. DISCUSSION: Understanding the perceptions of organizational directors
      may help identify opportunities for older adults to learn about community
      services and for providers to better coordinate care.

PMID- 30117352
TI  - Family Satisfaction With Nursing Home Care: Findings and Implications From Two
      State Comparison.
AB  - Family satisfaction, while recognized as important, is frequently missing from
      validated measures of long-term care quality. This is the first study to compare
      family satisfaction across two states using validated measures and to compare the
      organizational and structural factors associated with higher family satisfaction
      with nursing home care. Data sources are family satisfaction surveys from
      Minnesota (MN) and Ohio (OH), linked to facility characteristics from
      Certification and Survey Provider Enhanced Reports (CASPER) for both states ( N =
      378 facilities for MN; N = 926 facilities for OH). Activities and food were among
      lowest rated items in both states. Relationships with staff were the highest
      rated domain. Higher occupancy rates, smaller facility size, and non-profit
      ownership consistently predicted better satisfaction in both states. Our findings
      show consistent organizational factors associated with family satisfaction and
      provide further evidence to the validity of family satisfaction as a person
      centered measure of quality. This lays the foundation for tool development on the
      national level.

PMID- 30117353
TI  - Delivery Outcomes, Emergency Room Visits, and Psychological Aspects of
      Gestational Diabetes: Results From a Community Hospital Multiethnic Cohort.
AB  - Purpose The purpose of this study was to evaluate perinatal outcomes and
      experiences of managing gestational diabetes (GDM) in a multiethnic cohort from a
      community hospital. Methods A retrospective cohort study of 647 ethnically
      diverse women with GDM was conducted. Multivariable logistic regression models
      were used to examine ethnic differences in cesarean delivery rates and emergency
      department (ED) utilization during pregnancy. Semi-structured interviews were
      conducted to evaluate experiences of GDM and perceptions of type 2 diabetes risk.
      Results Significant differences were observed between sample groups in mother's
      age ( P = .004), education level ( P < .001), family history of diabetes ( P <
      .001), and baby birthweight ( P = .004). In the fully adjusted model, controlling
      for maternal age, BMI category, ED utilization during pregnancy, and family
      history of diabetes, Southeast and East Asian women had the lowest rates of
      cesarean delivery and ED utilization during pregnancy, with significantly higher
      rates of cesarean delivery in Hispanic, non-Hispanic white, and Asian Indian
      women ( P < .001). There was preliminary evidence for higher ED utilization rates
      during pregnancy in Hispanic women with GDM (odds ratio = 3.21; 95% CI, 0.79
      4.08; P = .005). Interview analyses reflected strong psychological impact of GDM
      diagnoses. Women expressed shock and disappointment over diagnoses and
      highlighted need for psychological support from health care professionals. Risk
      perceptions for type 2 diabetes were low. Conclusions Findings support
      significant ethnic differences in cesarean delivery and ED utilization among
      women with GDM. Qualitative analysis suggests that culturally sensitive
      approaches informing psychosocial support and dietary recommendations are
      important considerations for a diverse GDM patient population.

PMID- 30117354
TI  - Patterns of Aggressive Behaviors Across Mental Health in Sixth Graders.
AB  - School-based violence is a current public concern in the United States. One
      factor that can impact school-based violence that has gained much attention is
      mental health status. To better inform public perceptions, this study provides
      new evidence concerning the association between mental health status and acting
      out violence in school-aged populations. We examined a diverse sample of sixth
      graders across 14 schools in Texas in 2011-2012 ( N = 721) who completed a self
      administered survey assessing mental health symptoms and frequency of
      perpetration and/or receipt of different types of aggressive behaviors.
      Multinomial regression models tested whether adolescents with mental health
      symptoms (overall and by symptom types) are more predisposed to be actors only,
      recipients only, or both, of physical, verbal, and relational aggression. Across
      aggressive behavior types, symptomatic versus nonsymptomatic adolescents had
      consistently increased odds of being exclusively a recipient of aggression. When
      symptomatic adolescents did act out aggression, they participated concurrently as
      both an actor and recipient. Rarely were symptomatic adolescents more likely to
      be exclusively an actor of aggression. Moreover, symptomatic versus
      nonsymptomatic adolescents had five times the odds of being threatened by a
      weapon including a gun or knife. Compared to those who do not, youth who perceive
      having a mental health issue had twice the odds of being an actor only of verbal
      and relational aggression. These findings provide evidence for the need to change
      how the public associates mental health problems with aggressive behaviors among
      youth especially following national tragic events. Communities at large may
      benefit from evidence- and school-based interventions that improve awareness of
      and tolerance to mental health conditions among youth.

PMID- 30117355
TI  - Accuracy and Acceptability of Commercial-Grade Physical Activity Monitors in
      Older Adults.
AB  - The aim of this study was to evaluate accuracy of seven commercial activity
      monitors in measuring steps in older adults with varying walking abilities and to
      assess monitor acceptability and usability. Forty-three participants (age = 87 +/
      5.7 years) completed a gait speed assessment, two walking trials while wearing
      the activity monitors, and questionnaires about usability features and activity
      monitor preferences. The Accusplit AX2710 Accelerometer Pedometer had the highest
      accuracy (93.68% +/- 13.95%), whereas the Fitbit Charge had the lowest (39.12% +/
      40.3%). Device accuracy varied based on assistive device use, and none of the
      monitors were accurate at gait speeds <0.08 m/s. Barriers to monitor usability
      included inability to apply monitor and access the step display. Monitor accuracy
      was rated as the most important feature, and ability to interface with a smart
      device was the least important feature. This study identified the limitations of
      the current commercial activity monitors in both step counting accuracy and
      usability features for older adults.

PMID- 30117356
TI  - TGFbeta1: Friend or Foe During Recovery in Encephalopathy.
AB  - The cytokine transforming growth factor (TGF)-beta1 is highly induced after
      encephalopathic brain injury, with data showing that it can both contribute to
      the pathophysiology and aid in disease resolution. In the immature brain,
      sustained TGFbeta-signaling after injury may prolong inflammation to both
      exacerbate acute stage damage and perturb the normal course of development. Yet
      in adult encephalopathy, elevated TGFbeta1 may promote a reparative state. In
      this review, we highlight the context-dependent actions of TGFbeta-signaling in
      the brain during resolution of encephalopathy and focus on neuronal survival
      mechanisms that are affected by TGFbeta1. We discuss the mechanisms that
      contribute to the disparate actions of TGFbeta1 toward elucidating the long-term
      neurological and neuropsychiatric consequences that follow encephalopathic
      injury.

PMID- 30117357
TI  - Undiagnosed Obstructive Sleep Apnoea and Physical Activity in Older Manual
      Workers.
AB  - Cardiovascular disease (CVD) is a negative health outcome of Obstructive Sleep
      Apnoea (OSA). Risk factors associated with OSA development include low physical
      activity (PA), high body mass index (BMI), and increasing age (>50 years) and
      weight loss is usually recommended as treatment. This cross-sectional study
      examined the association between PA, BMI and OSA severity in manual workers.
      Fifty-five participants, (23 females, 32 males) mean age 55.2, were examined for
      OSA and completed a PA and anthropometric assessment. On average, OSA severity
      was mild, PA levels were moderate and 32% of the sample was classified as obese.
      PA was negatively associated with OSA severity, but BMI strongly independently
      predicted OSA severity, with no evidence of mediation. As both PA and BMI were
      significantly associated with OSA in older manual workers, increasing PA should
      also be a focus of treatment for OSA.

PMID- 30117358
TI  - A Modification of the Stapled TransAnal Rectal Resection (STARR) Procedure for
      Rectal Prolapse.
AB  - PURPOSE: This study was designed to assess the safety, efficacy, and
      postoperative outcomes of the modified Stapled TransAnal Rectal Resection
      (modified STARR) in patients presenting with cases of limited external rectal
      prolapse. METHODS: A prospective cohort of patients with mild rectal prolapse
      undergoing rectal resection with the Tissue-Selecting Technique Stapled TransAnal
      Rectal Resection Plus (TSTStarr Plus) stapler between February 2014 and September
      2016 was reviewed retrospectively. RESULTS: Twenty-five eligible patients
      underwent rectal resection with the TSTStarr Plus stapler. The median vertical
      height of the resected specimen was 5.0 cm (range = 3.1-10 cm) with all cases
      being confirmed histologically as full-thickness resections. Over a follow-up of
      33.6 +/- 9.4 months, only 1 case (4%) was encountered with recurrence. The mean
      postoperative Wexner score was significantly improved when compared with the
      preoperative scores (preoperative: median = 3, range = 0-20, vs postoperative:
      median = 2, range = 0-20, respectively; P = .010). The median preoperative
      Symptom Severity Score and Obstructed Defecation Score were both decreased
      compared with the postoperative scores ( P = .001). CONCLUSIONS: Modified STARR
      in management of mild rectal prolapse appear to be a safe and effective
      technique. The initial results would encourage a more formal prospective
      assessment of this technique as part of a randomized trial for the management of
      mild rectal prolapse.

PMID- 30117359
TI  - Validation of the Timed Up and Go Test for Assessing Balance Variables in Adults
      Aged 65 and Older.
AB  - The Timed Up and Go (TUG) Test is recommended by the U.S. Centers for Disease
      Control and Prevention as an easy to administer clinical test to evaluate a
      senior citizen's fall risk. Limited evidence has been presented in the literature
      validating the TUG Test. In this study we sought to assess correlations between
      the TUG Test and various balance markers utilizing the OptoGait system. Fifty-one
      healthy seniors completed randomized trials of the TUG Test and a Gait Test
      utilizing OptoGait photoelectric technology. Correlations among mean and standard
      deviation values for these variables and TUG performance were calculated.
      Utilizing a Bonferroni adjustment and an alpha level of .05, eight significant
      correlations of a moderately strong degree (absolute r scores between .51 and
      .78) emerged. Correlation results indicate that the TUG Test is a valid tool for
      screening balance deficits that lead to increased fall risk in senior citizens.

PMID- 30117360
TI  - Impaired cerebral autoregulation and neurovascular coupling in middle cerebral
      artery stroke: Influence of severity?
AB  - We aimed to assess cerebral autoregulation (CA) and neurovascular coupling (NVC)
      in stroke patients of differing severity comparing responses to healthy controls
      and explore the association between CA and NVC with functional outcome. Patients
      admitted with middle cerebral artery (MCA) stroke and healthy controls were
      recruited. Stroke severity was defined by the National Institutes of Health
      Stroke Scale (NIHSS) scores: <=4 mild, 5-15 moderate and >=16 severe.
      Transcranial Doppler ultrasound and Finometer recorded MCA cerebral blood flow
      velocity (CBFv) and blood pressure, respectively, over 5 min baseline and 1 min
      passive movement of the elbow to calculate the autoregulation index (ARI) and
      CBFv amplitude responses to movement. All participants were followed up for three
      months. A total of 87 participants enrolled in the study, including 15 mild, 27
      moderate and 13 severe stroke patients, and 32 control subjects. ARI was lower in
      the affected hemisphere (AH) of moderate and severe stroke groups. Decreased NVC
      was seen bilaterally in all stroke groups. CA and NVC correlated with stroke
      severity and functional outcome. CBFv regulation is significantly impaired in
      acute stroke, and further compromised with increasing stroke severity. Preserved
      CA and NVC in the acute period were associated with improved three-month
      functional outcome.

PMID- 30117361
TI  - Outcomes after Concussion Recovery Education: Effects of Litigation and
      Disability Status on Maintenance of Symptoms.
AB  - This study examined the hypothesis that people who receive concussion recovery
      education would have better outcomes than those who received usual discharge
      paperwork from the emergency department (ED) and tested whether participants who
      were in litigation or seeking disability compensation had more symptoms than
      individuals not engaged in these activities. Two hundred and fifty-five persons
      with a diagnosis of concussion were assigned randomly to a brief education group
      (one-page double-sided document), a longer education group (10-page document),
      and usual care (standard ED discharge instructions), and were these documents in
      the ED. A (non-concussion) trauma comparison group was enrolled to determine the
      symptom rate unrelated to brain injury. The Concussion Symptom Checklist (CSC)
      and litigation and disability status questions were completed by telephone at one
      week, three months, and six months. Neither long nor brief information handouts
      had a significant impact on symptoms over time; the standard form had an average
      decrease of 1.20 symptoms compared with the brief instructional intervention
      group (p = 0.031). Litigation status and disability seeking status were
      significant predictors of symptoms on CSC over time: disability seeking (p =
      0.017) and litigation status (p = 0.05). Persons seeking Social Security
      disability or legal compensation endorsed more symptoms over time than those who
      were not. Number of symptoms on the CSC for the trauma control group was the same
      as those who sustained concussion. Type of recovery material was not as important
      as noting that concussion symptoms resolve over time, and that remaining symptoms
      are not specific to brain injury. Litigation and disability seeking behavior
      accounted for maintained symptoms, rather than the concussion itself.

PMID- 30117362
TI  - Attitudes and Experiences of Men with Prostate Cancer on Risk in the Context of
      Injuries Related to Community-based Football - A Qualitative Study.
AB  - While football training may be a potent strategy for health promotion in older
      men, the considerable risk of injuries may constitute a barrier for referral of
      clinical populations. The current study explored the attitudes of men with
      prostate cancer on risk in the context of injuries related to participating in a
      community-based football program. Four videotaped focus group interviews, and
      three individual in-depth telephone interviews were carried out with men with
      prostate cancer (n=35; mean age 68.8). Thematic networks technique was used to
      derive the global theme Injury-induced reinforced masculinity comprising five sub
      themes: "Part of the game", "A good story to tell", "Like boys again", "An old,
      carefree body", and "Camaraderie". Collectively, these themes explained how
      football injuries may reflect masculine ideals in some men with prostate cancer.
      The study indicates that injuries are largely acceptable to men with prostate
      cancer, especially those in search of a means for expressing their masculinity.

PMID- 30117363
TI  - Vascular access surgery can be safely performed in an ambulatory setting.
AB  - INTRODUCTION: Ambulatory surgery is associated with lower costs, but there is
      lack of evidence of the safety for ambulatory vascular access surgery. The
      objective of this study is to substantiate the safety and effectiveness of
      performing vascular access surgery in an ambulatory setting. METHODS: A review of
      our prospectively maintained database including all vascular access open
      surgeries (creations and repairs) performed by our Vascular Access Unit between
      2013 and 2017 was compiled. Patient comorbidities, surgery details, hospital
      admission conditions, and 1-week and 1-month follow-up patency and complications
      (death, infection, bleeding, and readmission/reintervention) were scrutinized.
      RESULTS: In the last 5 years, 1414 vascular access procedures were performed
      (67.8% access creations, 32.2% previous access repairs) in 1012 patients. Most
      surgeries were performed under local anesthesia (59.2%) or axillary plexus block
      (38.4%) and mainly in an ambulatory setting, without overnight hospital stays
      (90.9%). During the first postoperative week follow-up, 9 cases (0.6%) needed
      readmission or reintervention; significant infection materialized in 11 (0.8%)
      and 10 cases (0.7%) showed noteworthy hematoma or bleeding, only three (0.2%)
      requiring reintervention. The primary composite endpoint of 24-h death and 1 week
      readmission, reintervention, infection, or bleeding was 1.9% (27 cases); 1-month
      access failure was 6.2%. After univariate analysis, ambulatory settings were not
      related to higher rates of complications or readmissions. CONCLUSION:
      Arteriovenous access surgery can be safely performed in an ambulatory setting, in
      spite of complex cases, comorbidities, or the increasing implementation of
      axillary plexus blocks. Surgical results and patency are good, and complications
      necessitating readmission remain very low.

PMID- 30117364
TI  - Primary Use of the TruePath Crossing Device for Infrainguinal Chronic Total
      Occlusions With Intravascular Ultrasound Evaluation.
AB  - PURPOSE: To evaluate the use of the TruePath crossing device as the primary
      recanalization tool for infrainguinal chronic total occlusions (CTO). METHODS: A
      retrospective analysis was conducted of 50 patients (mean age 75 years; 26 men)
      with 55 infrainguinal CTOs treated with the TruePath between March 2017 and
      September 2017 at a single center. The mean occlusion length was 138+/-55 mm, and
      femoropopliteal lesions accounted for 65% of the 55 lesions. The primary outcome
      measure was CTO crossing using the TruePath alone; secondary outcomes were
      assisted success (>50% lumen gain using the TruePath), device-related
      complications, and intraluminal crossing evaluated by intravascular ultrasound
      (IVUS). RESULTS: Complete success was achieved in 33 (60%) of 55 lesions having a
      mean occlusion length of 145+/-72 mm. Among these, the true lumen crossing rate
      was 97% according to IVUS evaluation. Assisted success was achieved in 15 (68%)
      of the 22 failures. Complete/assisted success, in which the TruePath was thought
      to have contributed to CTO crossing, was attained in 48 (87%) of the 55 lesions.
      Three (5.5%) complications were observed: a perforation, an access-site hematoma,
      and acute occlusion; only the perforation was device related (1.8%). Multivariate
      analysis showed PACCS grade 4 (odds ratio 4.5, 95% confidence interval 1.33 to
      15.5, p=0.02) was an independent predictor of TruePath failure. CONCLUSION:
      Primary use of the TruePath crossing device for infrainguinal CTOs demonstrated a
      satisfactory complete success rate and a high rate of IVUS-documented
      intraluminal crossing with few device-related complications. Severe calcification
      is an independent predictor of TruePath failure.

PMID- 30117365
TI  - The Effects of Omega-3 and Branched-Chain Amino Acids Supplementation on Serum
      Apoptosis Markers Following Acute Resistance Exercise in Old Men.
AB  - The potential benefits of omega-3 fatty acids and branched-chain amino acids
      (BCAAs) supplements on exercise-induced apoptosis are not clear. In a crossover
      randomized study, 11 men (age = 62.8 +/- 2.2 years) performed an acute bout of
      resistance exercise and underwent 1-week supplementation with either 20 g of BCAA
      or 2,700 mg of omega-3/day. Subjects performed the same exercise after
      supplementation protocols. Following a 3-week washout period, subjects switched
      groups. Circulating levels of soluble Fas ligand (sFasL), cytochrome c, Bax, Bcl
      2, and nuclear factor-kappa B were measured before and immediately after exercise
      sessions. sFasL, cytochrome c, and Bax increased after exercise. Simple main
      effect of time on sFasl was significant in control trial but not in omega-3 and
      BCAA trials. There were no differences in nuclear factor-kappa B and Bcl-2
      between control and supplement trials. This study showed that adding omega-3
      fatty acids or BCAA to the dietary regime of old men could partially attenuate
      resistance exercise-induced apoptosis.

PMID- 30117366
TI  - Signal-to-Noise-Ratio-Aware Dynamic Range Compression in Hearing Aids.
AB  - Fast-acting dynamic range compression is a level-dependent amplification scheme
      which aims to restore audibility for hearing-impaired listeners. However, when
      being applied to noisy speech at positive signal-to-noise ratios (SNRs), the gain
      function typically changes rapidly over time as it is driven by the short-term
      fluctuations of the speech signal. This leads to an amplification of the noise
      components in the speech gaps, which reduces the output SNR and distorts the
      acoustic properties of the background noise. An adaptive compression scheme is
      proposed here which utilizes information about the SNR in different frequency
      channels to adaptively change the characteristics of the compressor.
      Specifically, fast-acting compression is applied to speech-dominated time
      frequency (T-F) units where the SNR is high, while slow-acting compression is
      used to effectively linearize the processing for noise-dominated T-F units where
      the SNR is low. A systematic evaluation of this SNR-aware compression scheme
      showed that the effective compression of speech components embedded in noise was
      similar to that of a conventional fast-acting system, whereas natural
      fluctuations in the background noise were preserved in a similar way as when a
      slow-acting compressor was applied.

PMID- 30117368
TI  - Mere Exposure Effects on Implicit Stimulus Evaluation: The Moderating Role of
      Evaluation Task, Number of Stimulus Presentations, and Memory for Presentation
      Frequency.
AB  - The mere exposure (ME) effect refers to the well-established finding that people
      evaluate a stimulus more positively after repeated exposure to it. So far, the
      vast majority of studies on ME effects have examined changes in explicit stimulus
      evaluation. We describe the results of three large-scale studies (combined N =
      3,623) that examined ME effects on implicit stimulus evaluation. We looked at
      three moderators of these effects: the implicit evaluation measure, the number of
      stimulus presentations, and memory for presentation frequency. We observed ME
      effects on implicit stimulus evaluations as measured with an Implicit Association
      Test (IAT) and Affect Misattribution Procedure (AMP), but not an Evaluative
      Priming Task (EPT). ME effects were more robust when there were relatively few
      stimulus presentations and when participants had accurate memory for the
      presentation frequencies. We discuss how these findings relate to ME effects on
      explicit evaluations as well as theoretical and practical implications.

PMID- 30117369
TI  - Cancer precision medicine today: Towards omic information in healthcare systems.
AB  - INTRODUCTION: This article focuses on the integration of omics data in electronic
      health records and on interoperability aspects relating to big data analysis for
      precision medicine. METHODS: Omics data integration methods for electronic health
      record and for systems interoperability are considered, with special reference to
      the high number of specific software tools used to manage different aspects of
      patient treatment. This is an important barrier against the use of this
      integrated approach in daily clinical routine. RESULTS: The correct use of all
      three levels of interoperability (technical, semantic, and process
      interoperability) plays a key role in order to achieve an easy access to a
      significant amount of data, all with correct contextualization, which is the only
      way to obtain a real value from data for precision medicine. CONCLUSIONS: The
      proposed architecture could improve the potentialities of data routinely
      collected in many health information systems to form a real patient center
      information environment.

PMID- 30117370
TI  - A Fulbrighter's Journey.

PMID- 30117367
TI  - The Effects of Ramadan-Fasting (RF) on Inflammatory and Hematological Indices of
      Stable Chronic Obstructive Pulmonary Disease (COPD) Male Patients: A Pilot Study.
AB  - No previous study has evaluated the effects of RF on inflammatory and
      hematological indices of COPD patients. The main objective of the present pilot
      study was to assess the effects of RF on some inflammatory and hematological
      indices measured in male patients with stable COPD. Fifteen COPD patients (mean
      +/- SD of age: 71 +/- 6 years) who fasted during Ramadan 2017 volunteered for the
      study. Three sessions (Before-Ramadan, End-Ramadan and After-Ramadan) were
      selected. Spirometry tests and blood samples were consistently performed 2.5-4.5
      hr before the interruption of the fasting. Assessment sessions comprised:
      spirometry, inflammatory [erythrocyte sedimentation rate (ESR); C-reactive
      protein (CRP)] and hematological [red and white blood cells (RBC, WBC);
      hemoglobin; hematocrit; mean corpuscular volume; mean corpuscular hemoglobin;
      platelets] indices. Findings were analyzed by applying Friedman ANOVA. The median
      (lower-upper quartiles) of ESR (Before-Ramadan: 3 (2-9), End-Ramadan: 7 (0-13),
      After-Ramadan: 9 (5-15) mm/h) and CRP (Before-Ramadan: 20 (11-38), End-Ramadan:
      15 (9-34), After-Ramadan: 20 (12-46) mg/L) were not significantly affected by RF.
      Among all the hematological indices, RF influenced only hemoglobin (Before
      Ramadan: 14.4 +/- 2.2, End-Ramadan: 13.4 +/- 1.3, After-Ramadan: 12.2 +/- 0.9
      g/dL), hematocrit (Before-Ramadan: 45 +/- 7, End-Ramadan: 40 +/- 4, After
      Ramadan: 39 +/- 4%), RBC (Before-Ramadan: 5.1 +/- 1.0, End-Ramadan: 4.6 +/- 0.7,
      After-Ramadan: 4.4 +/- 0.5 106/mm3) and WBC (Before-Ramadan: 8,673 +/- 1,911, End
      Ramadan: 7,840 +/- 1,526, After-Ramadan: 9,507 +/- 2,190/mm3). Compared to the
      Before-Ramadan session, the End-Ramadan session values for hemoglobin,
      hematocrit, RBC and WBC were lower. Compared to the After-Ramadan session, the
      End-Ramadan session values for hemoglobin and WBC were higher and lower,
      respectively. In conclusion, RF caused significant reduction in hemoglobin,
      hematocrit, RBC and WBC. However, it did not induce any significant changes in
      the CRP and ESR indices.

PMID- 30117371
TI  - Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in rectal
      cancer patients following neoadjuvant chemoradiotherapy.
AB  - PURPOSE: There is uncertainty over the effect of systemic inflammatory response
      on oncologic outcomes in patients who underwent neoadjuvant chemoradiotherapy and
      surgery for rectal cancer. We investigated the association between neutrophil
      lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) as markers of systemic
      inflammation and tumor response and prognosis after treatment. METHODS: A total
      of 176 patients who underwent neoadjuvant chemoradiotherapy and curative surgery
      for rectal cancer were analyzed retrospectively. Pretreatment hematologic
      parameters and the main clinical factors for patients and tumors were
      investigated with respect to their relationship with tumor regression and
      survival. RESULTS: In the receiver operating characteristic analysis, NLR 2.0 and
      PLR 133.4 had the highest sensitivity and specificity in predicting tumor
      response. NLR <2.0 and PLR <133.4 were significantly correlated with good tumor
      response (odds ratio [OR] 2.490, 95% confidence interval [CI] 1.264-4.904, p =
      .008; OR 3.009, 95% CI 1.477-6.127, p < .001). Patients with NLR <2.0 had
      significantly better 5-year disease-free survival rate and overall survival rate
      compared to patients with NLR ?2.0 in multivariate analysis (86.8% vs 70.7%, p =
      .014; 92.4% vs 71.9%, p = .027). CONCLUSIONS: Elevated NLR and PLR levels can be
      considered as predictors of poor pathologic response, and NLR can be considered a
      prognosticator in patients who underwent neoadjuvant chemoradiotherapy for
      locally advanced rectal cancer.

PMID- 30117372
TI  - Update on small bowel surveillance in hereditary colorectal cancer syndromes.
AB  - Despite its rarity in the general population, small bowel adenocarcinoma risk is
      increased in individuals with hereditary colorectal cancer syndromes (HCCS). In
      the last decade, the advent of capsule endoscopy and device-assisted balloon
      enteroscopy procedures in patients with HCCS have allowed to investigate the
      whole small bowel, increasing the diagnostic yield of small bowel tumor.
      Nonetheless, there is a significant variability in the international guideline
      recommendations. The aim of this review is to provide an update on surveillance
      of small bowel in HCCS and to identify the key points for the clinical management
      of these patients.

PMID- 30117374
TI  - Committees.

PMID- 30117373
TI  - The self-reported and observed competence of nursing staff in mobility care based
      on Kinaesthetics in nursing homes - A cross-sectional study.
AB  - BACKGROUND: The majority of care-dependent persons living in nursing homes have
      mobility impairment affecting the physical, psychological, and social aspects of
      the persons' lives. Therefore, nursing staff needs competence to provide good
      mobility enhancing care. AIM: This study assesses the self-reported and observed
      competence of nursing home staff in mobility care based on Kinaesthetics in order
      to increase attention about nursing staff's impact on nursing home residents'
      mobility. METHODS: A cross-sectional study design involving a survey and an
      observational study was employed. Survey data were collected using the
      Kinaesthetics Competence Self-Evaluation (KCSE) scale. For the observational
      study, data were collected with a video camera and rated using the Kinaesthetics
      Competence Observation (KCO) instrument. Data were analysed using descriptive
      statistics, correlation methods and a generalised linear model. RESULTS: The
      majority of survey participants (n = 180) indicated their competence in mobility
      care based on Kinaesthetics as very good (mean score 13, SD 1.44, on a scale from
      4 to 16). The observed competence of nursing staff (n = 40) was good (mean score
      10.8, SD 2.44, out of a possible score from 4 to 16). Positive correlations were
      found between self-reported or observed competence in mobility care based on
      Kinaesthetics and employment rate, work experience in nursing home care and
      Kinaesthetics training. CONCLUSION: A combined assessment of self-evaluation and
      observation is recommended in order to get a comprehensive picture of knowledge,
      skills, attitude and dynamic state of nursing staffs' competence in mobility care
      based on Kinaesthetics.

PMID- 30117375
TI  - SPCAL 2018 abstract book.

PMID- 30117377
TI  - "What shall I do when I grow up?" Adolescents with cancer on the Youth Project in
      Milan play with their imagination and photography.
AB  - INTRODUCTION: Adolescents diagnosed with cancer have to temporarily stop pursuing
      several vital needs and making plans for the future. The Youth Project in Milan,
      Italy, focuses on such issues in young cancer patients' personal lives.
      Uncertainty about the future had already emerged in several artistic projects
      designed to help these patients voice their emotions. METHODS: We describe a
      project revolving around the question "What shall I do when I grow up?" Twenty
      seven 15- to 26-year-old patients wrote a brief account of what they hoped to do
      as adults. Using theatrical costumes, they then dressed up in their chosen role
      for a photo shoot with a well-known professional photographer. The results were
      published in one of Italy's main national dailies. RESULTS: Participants reacted
      differently: some lightheartedly, others more seriously. They often expressed the
      wish to help others, desiring to return the support and protection they had
      received as patients. Another common theme concerned their need for normality.
      CONCLUSION: By writing about their dreams, these patients gave their doctors a
      glimpse of their inner world. The project proved an important complement to more
      conventional forms of psychosocial support and interaction with young patients.

PMID- 30117379
TI  - Executive attention moderates the effect of trait anxiety on hyperarousal
      symptoms.
AB  - The majority of individuals exposed to trauma do not go on to develop
      posttraumatic stress disorder (PTSD); thus, researchers have sought to identify
      individual difference variables that make one particularly susceptible to
      posttraumatic stress symptoms. Trait anxiety is one individual difference
      variable implicated in the pathogenesis of posttraumatic stress symptoms.
      Following from cognitive theories of anxiety and extant data, the purpose of the
      present study was to examine executive attention as a moderator of the relation
      between trait anxiety and posttraumatic stress symptoms, particularly
      hyperarousal symptoms, among undergraduate women reporting trauma exposure (N =
      88). As predicted, executive attention moderated the association between trait
      anxiety and hyperarousal symptoms, such that there was a significantly weaker
      relation as executive attention increased. Study results further support the
      potential buffering effect of executive attention in relation to posttraumatic
      stress symptoms, as well as the possible importance of targeting executive
      attention following trauma exposure.

PMID- 30117378
TI  - Performance of tumor testing for Lynch syndrome identification in patients with
      colorectal cancer: A retrospective single-center study.
AB  - OBJECTIVE: To investigate the performance of tumor testing approaches in the
      identification of Lynch syndrome (LS) in a single-center cohort of people with
      colorectal cancer (CRC). METHODS: A retrospective analysis of data stored in a
      dedicated database was carried out to identify patients with CRC suspected for LS
      who were referred to Fondazione IRCCS Istituto Nazionale dei Tumori, Milan,
      Italy, between 1999 and 2014. The sensitivity and specificity of
      immunohistochemistry (IHC) for mismatch repair (MMR) proteins and microsatellite
      instability (MSI) analysis (alone or combined) were calculated with respect to
      the presence of causative MMR germline variants. RESULTS: A total of 683 patients
      with CRC suspected for LS were identified. IHC results of MMR protein analysis
      and MSI were assessed in 593 and 525 CRCs, respectively, while germline analysis
      was performed in 418 patients based on the IHC or MSI test result and/or clinical
      features. Univariate and multivariate analysis revealed a significant correlation
      of pathogenic MMR germline variants with all clinicopathologic features including
      Amsterdam criteria, presence of endometrial cancer, CRC site, age at onset,
      stage, and grade. The highest odds ratio values were observed for IHC and MSI
      (17.1 and 8.8, respectively). The receiver operating characteristic curve and
      area under the curve values demonstrated that IHC alone or combined with other
      clinicopathologic parameters was an excellent test for LS identification.
      CONCLUSIONS: This study confirms the effectiveness of tumor testing to identify
      LS among patients with CRC. Although IHC and MSI analysis were similarly
      effective, IHC could be a better strategy for LS identification as it is less
      expensive and more feasible.

PMID- 30117380
TI  - Development of bidirectional phono-semantic activation in toddlers.
AB  - A mediated priming effect refers to the activation of a target via a mediator
      previously activated by a prime. This effect has been found at 24 months of age
      for phono-semantic links: a prime ( cup) activates a target ( dog) via a mediator
      ( cat), providing evidence of activation in a forward direction (phonological to
      semantic). Interactive models, however, propose that activation propagates in
      both forward and backward directions between processing levels. This study
      investigated the development of bidirectional co-activation of phonological and
      semantic levels of processing in Spanish-speaking toddlers. In a primed
      preferential looking task, participants were exposed to an unlabelled prime
      image, followed by the presentation of two images, a target and a distractor. In
      Experiment 1, when images with a semantic-phonological relationship were
      presented, both 24- and 30-month-olds preferred to look at the named target with
      a relationship to the prime image ( dog- cat- cup). However, when an unrelated
      target image was named, 24-month-olds preferred to look at the target, but 30
      month-olds did not. In Experiment 2, both 24- and 30-month-olds preferred to look
      at a target with a phono-semantic relationship to the prime ( cup- cat- dog) over
      an unrelated target. These results provide strong evidence of differences in the
      development of forward and backward interactions between semantic and
      phonological processing levels.

PMID- 30117381
TI  - "17" is odd and "seventeen" is even: Meaning and physical form in stimulus-parity
      synaesthesia.
AB  - For individuals with stimulus-parity synaesthesia, eliciting stimuli (e.g.,
      shapes, numbers, letters, colours) trigger a compelling feeling of oddness or
      evenness. Given that (a) many inducers are conceptual and (b) parity is itself a
      conceptual property, one questions whether stimulus-parity synaesthesia will be a
      categorically higher subtype, such that the conceptual properties of stimuli will
      be crucial in determining parity. We explore this question as it applies to
      Synaesthete R, one of only two stimulus-parity synaesthetes known to the
      contemporary literature. In Experiments 1 and 2, we examine whether parity is
      tied to concepts or percepts, asking, for example, whether a rectangle is even
      regardless of whether it is presented as an image or a word. Our results indicate
      that the parity of shapes (words and images), numbers (words, digits, and Roman
      numerals), and letters (lowercase and uppercase) differs according to the
      stimulus format, supporting a perceptual explanation. In Experiment 3, we examine
      the parity of colour stimuli, showing a systematic relationship between the
      measurable physical properties of hue, saturation, and lightness and synaesthetic
      parity. Despite the conceptual nature of inducers and concurrents, for
      Synaesthete R, stimulus-parity synaesthesia is a lower subtype; perceptual
      properties of stimuli determine parity.

PMID- 30117382
TI  - The role of lexical variables in the visual recognition of two-character Chinese
      compound words: A megastudy analysis.
AB  - To examine the effect of lexical variables on two-character Chinese compound word
      processing, we performed item-level hierarchical regression analyses on lexical
      decision megastudy data of 18,983 two-character Chinese compound words. The first
      analysis determined the unique item-level variance explained by orthographic
      (frequency and stroke count), phonological (consistency, homophonic density), and
      semantic (transparency) variables. Both character and word variables were
      considered. Results showed that orthographic and semantic variables,
      respectively, accounted for more collective variance than phonological variables,
      suggesting that Chinese skilled readers rely more on orthographic and semantic
      information than phonological information when processing visually presented
      words. The second analysis tested interactive effects of lexical variables and
      showed significant semantic transparency * cumulative character frequency and
      word frequency * cumulative character frequency interactions. The effect of
      cumulative character frequency was stronger for transparent words than for opaque
      words and was stronger for low-frequency words than for high-frequency words.
      However, there was no semantic transparency * word frequency interaction in
      reaction time. Implications of the current findings on models of Chinese compound
      word processing are discussed.

PMID- 30117383
TI  - Development of basic intuitions about physical support during early childhood:
      Evidence from a novel eye-tracking paradigm.
AB  - Using a novel eye-tracking paradigm, we assessed the development of 2- to 6-year
      old children's intuitions about the physical support of symmetrical and
      asymmetrical objects in two experiments (Experiment 1: N = 98; Experiment 2: N =
      288). Children were presented with video sequences demonstrating how two
      identical blocks were lowered onto a platform before being released
      simultaneously. In the critical test trials, both blocks remained in place
      although only one of them was sufficiently supported. As expected, children
      tended to look longer at the block, which should have fallen. Taken together, the
      results indicate that even 2-year-old children are sensitive to the amount of
      contact between symmetrical blocks and a supporting platform and even anticipate
      which block is going to fall. Nonetheless, we found a considerable improvement
      with age in this respect. Two-year-olds did not consider an object's weight
      distribution reliably when assessing its stability and even older preschoolers
      performed much more poorly with asymmetrical than symmetrical blocks. We conclude
      that intuitions about support are still weak and limited in toddlers and that
      they improve considerably during early childhood.

PMID- 30117384
TI  - Implicit false belief tracking is preserved in late adulthood.
AB  - It is now well established that relative to their younger counterparts, older
      adults experience difficulties on tasks that require the conscious and explicit
      processing of others' mental states (e.g., beliefs, intentions; theory of mind
      [ToM]). Despite the importance of relatively automatic and unconscious mental
      state attribution processes in everyday life, no study to date has tested whether
      tasks that require the implicit processing of others' belief states also show age
      related changes. In this study, younger and older adults completed an implicit
      false belief task, in which their eye movement patterns were monitored while they
      passively viewed true and false belief movies. In addition, they were assessed on
      measures of explicit ToM processing. While older adults showed impairments in
      explicit ToM processing relative to younger adults, both age groups demonstrated
      a similar capacity for implicit false belief processing. These findings suggest
      that implicit components of ToM are preserved in late adulthood and are
      consistent with dual process models of ageing that emphasise age-related
      stability in automatic processing and declines in more controlled and effortful
      cognitive operations. We discuss the potential implications of these findings for
      social interactions in old age.

PMID- 30117386
TI  - Multiple application of three-dimensional soft kidney models with localized
      kidney cancer: A pilot study.
AB  - AIM: To evaluate the effectiveness of three-dimensional printing application in
      urology for localized renal cancer treatment using three-dimensional printed soft
      models. MATERIALS AND METHODS: The study included five patients with kidney
      tumors. The patients were treated in the Urology Clinic of I.M. Sechenov First
      Moscow State Medical University from February 2016 to June 2017. Personalized
      three-dimensional printed models based on computed tomographic images were
      created. Five surgeons took part in a survey in which the utility of computed
      tomographic images versus three-dimensional printed models for presurgical
      planning was compared. A laparoscopic partial nephrectomy training using the
      developed three-dimensional printed models was performed by the same surgeons in
      a surgical training box. RESULTS: The patients underwent endoscopic surgery using
      laparoscopic access. The average time of surgery was 187 min. All the operations
      were performed with complete renal artery clamping. The average warm ischemia
      time was 19.5 min and the average blood loss was 170 mL. No conversions to open
      surgery or radical nephrectomy, and no postoperative complications and deaths
      were observed. All the surgical margins were negative. The tumors were
      morphologically identified as renal cell carcinoma in four cases and as
      oncocytoma in one case. CONCLUSION: The developed three-dimensional printed
      models allow one to evaluate the pathological anatomy of tumors more effectively.
      High similarity between three-dimensional models and native kidneys contribute to
      improvement of surgical skills necessary for partial nephrectomy. Training on the
      three-dimensional models also allows surgeons to facilitate selection of an
      optimal surgical tactics for each patient.

PMID- 30117387
TI  - Postoperative complications and 90-day mortality in radical cystectomy in high
      risk patients: A monocentric retrospective observational study.
AB  - AIM: Assessing the incidence of immediate postoperative complications and 90-day
      mortality in high-risk patients who have undergone radical cystectomy; evaluating
      the correlation between preoperative conditions and surgery outcomes. MATERIALS
      AND METHODS: This is a monocentric retrospective observational study in which
      data of 65 patients have been analyzed. High-risk criteria: (a) Age >=75 years,
      (b) obesity, (c) age-adjusted Charlson Comorbidity Index >=8, (d) anemic status,
      and (e) pT >=3. More than 50% of patients had two or more "high-risk" indicators.
      Postoperative complications were assessed through Clavien-Dindo classification.
      RESULTS: Average age of patients was 70.4 years, average age-adjusted Charlson
      Comorbidity Index was 5.8, and average body mass index was 27.5. In 28% of
      patients, no complications arose, while in 46% grades I-II complications
      according to Clavien-Dindo occurred, in 23% grades III-IV complications occurred,
      and in 3% of the patients, death arose in the immediate postoperative period
      (grade V). Overall, 90-day mortality rate after surgery was 12.3%. The age >=75
      years and an age-adjusted Charlson Comorbidity Index score >=8 have shown to be
      risk factors for the onset of severe complications (odds ratio = 3.54, p = 0.028
      and odds ratio = 4.7, p = 0.026), while preoperative anemic status was a risk
      factor for complications in general (odds ratio = 4.1, p = 0.015). No analyzed
      parameter was a predictor of 90-day mortality ( p > 0.05). CONCLUSION: Immediate
      postoperative complications and 90-day mortality in radical cystectomy in high
      risk patients remain significant, but still in line with the data in the
      literature on comparable populations. Some of the preoperative parameters were
      able to predict the outcomes of the intervention with regard to the onset of
      complications but not to the 90-day mortality.

PMID- 30117388
TI  - Emphysematous pyelonephritis: Case report and literature overview.
AB  - INTRODUCTION: Emphysematous pyelonephritis is a rare necrotizing infection of the
      kidney with a poor prognosis. If it occurs in patients with a reduced general
      condition, this infection is life threatening. Early diagnosis is made by
      computed tomography. Treatment options are drainage and intensive care or
      immediate nephrectomy in severe cases. CASE DESCRIPTION: A 73-year-old woman in a
      poor general condition presented with a fulminant urosepsis. Computed tomography
      revealed an impressive abscess formation of the right kidney with free air retro
      and intraperitoneal. The diagnosis of emphysematous pyelonephritis was made.
      Besides septicemia, she had a multiorgan failure including kidney and liver
      function deterioration. Nephrectomy was performed immediately. The postoperative
      course was successful with a complete stabilization of the kidney and liver
      function and reconvalescence of the patient. DISCUSSION: The widespread
      availability of imaging techniques leads to early diagnosis and a reduction of
      mortality of renal and periphrenic abscesses and even of emphysematous
      pyelonephritis. However, severe cases have a poor outcome and require aggressive
      and immediate therapy. Besides systemic antibiotic therapy and percutaneous and
      surgical drainage, radical nephrectomy is a viable therapy option and should be
      performed immediately in patients with several risk factors, poor prognosis, and
      extensive findings. CONCLUSION: Radical nephrectomy being performed immediately
      seems to be the optimal management in patients with acute emphysematous nephritis
      and urosepsis.

PMID- 30117389
TI  - A Simple and One-pot Synthesis of Tetrahydrobenzo[b]pyrans and Spirooxindoles
      Catalyzed by H-Fe3O4@DA-SO3H as an Efficient, Light and Reusable Nanocatalyst.
AB  - AIM AND OBJECTIVE: One of the principles of green chemistry is using inexpensive
      reagents and catalysts to design green route for synthesis of organic compounds.
      Recently magnetic nanoparticles have provided a considerable merits. In this
      study, hollow Fe3O4@Dopamine-SO3H has been successfully applied for the green
      synthesis of tetrahydrobenzo[b]pyrans and spirooxindoles via one-pot multi
      component reaction. MATERIALS AND METHODS: Chemical reagents were purchased from
      Merck and Aldrich. Melting points were determined using an Electrothermal 9100.
      Fourier transform infrared and NMR spectra were recorded with a Shimadzu 8400
      spectrometer and Bruker spectrometer, respectively. RESULTS: The reaction between
      benzaldehyde, malononitrile and dimedone was selected as the model for synthesis
      of tetrahydrobenzo[b]pyran. The obtained results showed that the best amount of
      catalyst is 0.01 g and the reaction has occurred in solvent free condition at 70
      degrees C. The results showed that both electron-withdrawing and electron
      donating substituents have an acceptable yield in the reaction. After that the
      scope of this method was evaluated in one-pot synthesis of spirooxindole
      derivatives through three-component reaction of isatin derivatives, malononitrile
      or ethyl cyanoacetate and 1,3-cycllic diketone. The optimum condition was 0.01 g
      catalyst using H2O under reflux condition. Then other derivatives produced in
      excellent yields during short reaction times. CONCLUSION: Tetrahydrobenzo[b]pyran
      and spirooxindole derivatives in the presence of this catalyst were synthesized.
      The ease of preparation and handling of the catalyst and operational simplicity
      are some of the main advantages of this work. In addition, the catalyst could be
      recycled and reused at least six times without notable reduction in its catalytic
      activity.

PMID- 30117390
TI  - Interindividual Variability in Drug Metabolizing Enzymes.

PMID- 30117391
TI  - Antioxidant, Antimicrobial and the Phenolic Content of Infusion, Decoction and
      Methanolic Extracts of Thyme and Rosmarinus Species.
AB  - BACKGROUND: The plant species Rosmarinus officinalis (RO), Thymus algeriensis
      (TA) and Thymus capitatus (TC) are widely used in traditional medicine in
      Tunisia. Their bioactivities have been reported before and particularly referred
      to their essential oils. The main objective of this work was to assess the
      phytochemical composition, the antioxidant activity, the antibacterial,
      antifungal, and cytotoxic potential of these 3 plants. METHOD: The High
      Performance Liquid Chromatography (HPLC), chemical tests and spectrophotometric
      methods were used for screening, quantification of phytochemicals and for
      antioxidant activities. Extracts were evaluated for antibacterial potential by
      the microdilution method. Antifungal activities were tested using the Poisoned
      food method against: Aspergillus niger and Aspergillus flavus. The cytotoxic
      potential of the plant extracts was checked using HCT 116 cultures. RESULTS:
      Results revealed that aqueous extracts are not toxic compared to the methanolic
      extracts. Phenolic compounds were detected and these extracts showed excellent
      antioxidant activity presenting dose-dependent relationship. For antibacterial
      potential, all tested strains are more sensitive to Thymus extracts than
      Rosmarinus extracts. However, for antifungal activities, only Rosmarinus extracts
      inhibited mycelial growth. HPLC analysis allowed the identification of ten
      compounds with the abundance of gallic acid. CONCLUSION: This study showed
      important bioactivities (antioxidant, antimicrobial, and safety potential) of the
      plant species RO, TA and TC used in traditional medicine.

PMID- 30117392
TI  - The evaluation of animal models in the development of anticancer agents : from
      preclinical to clinical tests.
AB  - BACKGROUND: one of the main reasons for the most of anticancer drugs fail in the
      late preclinical testing and early clinical trials is the differences in drug
      effects observed from animals and patients, and challenge has been to find a
      balance to reduce the inherent differences from species. OBJECTIVES: the animal
      toxicological studies of anticancer agents are aimed at predicting a safe
      starting dose and dosage regimen for human clinical trials. METHOD: relevant
      information and data were assimilated from manuscripts, congress publications,
      and online sources. RESULTS: we systematically overview the cons and pros of
      animal models and briefed the ways to determine human clinical starting doses
      derived from animal toxicological studies for anticancer drugs. CONCLUSION: these
      information helps smart select the suitable predictive model for anti-cancer
      drugs with the different mechanisms and emphasized the pharmaceutical challenges
      behind and ahead.

PMID- 30117393
TI  - Novel Classes of Antibacterial Drugs in Clinical Development, a Hope in a Post
      antibiotic Era.
AB  - Bacterial resistance is a growing problem worldwide and is estimated that deaths
      by infectious diseases associated with resistant pathogens will generate 10
      million deaths per year in 2050. This problem becomes more serious due to the low
      level of research and development of new drugs, which has fallen drastically in
      the last 40 years. For example, in the last decade of a total of 293 new drugs
      approved by the FDA, only 9 corresponded to antimicrobial drugs and none
      constituted a new structural class. The majority of the molecules in the clinical
      phase II or III, coming from modifications of drugs in clinical use, this
      strategy makes easier the bacterial susceptibility to generate resistance through
      the mechanisms expressed for their drug predecessors. Under this scenario, it is
      urgent to generate the most novel strategies for the development of antibacterial
      compounds with new targets or mechanism of action, without a structural
      relationship with the antibiotic drugs predecessors. Under this look, the present
      review addresses the development of the latest antibacterial drugs in clinical
      phases II and III, analyzing the design strategies by which these new molecules
      were obtained and the structure-activity relationship of these new families of
      antibiotics, in order to define the state of the vanguard antibacterial drugs in
      the post-antibiotic era.

PMID- 30117394
TI  - Overview of Free Software Developed for Designing Drugs Based on Protein-Small
      Molecules Interaction.
AB  - One of the fundamental challenges in designing drug molecule against a disease
      target or protein is to predict binding affinity between target and drug or small
      molecule. In this review, our focus will be on advancement in the field of
      protein-small molecule interaction. This review has been divided into four major
      sections. In the first section, we will cover software developed for protein
      structure prediction. This will include prediction of binding pockets and post
      translation modifications in proteins. In the second section, we will discuss
      software packages developed for predicting small-molecule interacting residues in
      a protein. Advances in the field of docking particularly advancement in the
      knowledgebased force fields will be discussed in the third part of the review.
      This section will also cover the method developed for predicting affinity between
      protein and drug molecules. The fourth section of the review will describe
      miscellaneous techniques used for designing drug molecules, like pharmacophore
      modelling. Our major emphasis in this review will be on computational tools that
      are available free for academic use.

PMID- 30117395
TI  - Role of Biomacromolecules in Biomedical Engineering.
AB  - Biomacromolecules structures and their interaction between different systems have
      been extensively studied in the last years. Nevertheless, in the medicinal
      context, it has not been studied deeply. For this reason, the interest to
      investigate the behavior of different biomacromolecules such us proteins,
      organelles, phospholipids, etc. with soft materials has opened new research
      lines. Computational and experimental methodologies have tried to answer
      different questions that have been difficult to solve, due to the complexity of
      the phenomenon, as an example, competition between biomacromolecules and soft
      materials for a specific organ. In this review, we would like to demonstrate how
      soft materials influence the biomacromolecules structures and how to change their
      response, biodistribution and also biocompatibility for future applications.

PMID- 30117396
TI  - Host Restriction Factors and Human Immunodeficiency Virus (HIV-1): A Dynamic
      Interplay Involving All Phases of the Viral Life Cycle.
AB  - Mammalian cells have evolved several mechanisms to prevent or block lentiviral
      infection and spread. Among the innate immune mechanisms, the signaling cascade
      triggered by type I interferon (IFN) plays a pivotal role in limiting the burden
      of HIV-1. In the presence of IFN, human cells upregulate the expression of a
      number of genes, referred to as IFN-stimulated genes (ISGs), many of them acting
      as antiviral restriction factors (RFs). RFs are dominant proteins that target
      different essential steps of the viral cycle, thereby providing an early line of
      defense against the virus. The identification and characterization of RFs have
      provided unique insights into the molecular biology of HIV-1, further revealing
      the complex host-pathogen interplay that characterizes the infection. The
      presence of RFs drove viral evolution, forcing the virus to develop specific
      proteins to counteract their activity. The knowledge of the mechanisms that
      prevent viral infection and their viral counterparts may offer new insights to
      improve current antiviral strategies. This review provides an overview of the RFs
      targeting HIV-1 replication and the mechanisms that regulate their expression as
      well as their impact on viral replication and the clinical course of the disease.

PMID- 30117397
TI  - Evaluation of risk factors associated with diabetic foot ulcers in Saudi Arabia.
AB  - BACKGROUND AND AIMS: Considering that diabetic foot ulceration is one of the
      major health issues globally, we aimed to evaluate the risk factors associated
      with foot ulcers in patients with type 2 diabetes mellitus (T2DM). METHODS: A
      total of 81 T2DM patients (age range: 40-80 years) registered at the Diabetes
      Treatment Center, Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi
      Arabia between April and September 2015 were included in this cross-sectional
      study after purposive selection and assigning of patient numbers. The selected
      participants were interviewed and examined, and their medical records were
      reviewed for sensory, vibratory, and painful neuropathies; vascular
      insufficiency; retinopathy; and dermatological variations. The Wagner's
      classification system was employed to evaluate the stage of patients' foot
      ulcers. RESULTS: Among the study participants [mean age range: 56.4 +/- 6.72
      years; 53 males (65.4%)], cases of loss of protective sensation, foot deformity,
      amputation history, and dermatological abnormalities were notable. The Wagner
      gradation value of ulcers were grade 0 for 16% study population, grade 1 for
      35.8%, grade 2 for 45.7%, grade 3 for 2.5%, and grades 4 and 5 for 0%.
      Approximately 19% of the patients had a previous case of amputation and 29.6% had
      nail disease. The most common footwear reported to be used by the patients was
      sandals shoes (46%). CONCLUSIONS: The issues of loss of protective sensation,
      vascular insufficiency, deformity, previous amputations, and dermatological
      abnormalities of the lower limbs were found to be most common among the foot
      ulceration patients. The study findings thus recommend regular foot examination,
      following of basic hygiene habits, encouragement of the use of appropriate
      footwear, patient education about foot ulcers, and prompt treatment for minor
      injuries to prevent further ulceration in DM patients.

PMID- 30117398
TI  - Potential Utility of Self-Report Measures of Affect to Optimise Exercise
      Adherence in People with Type 2 Diabetes.
AB  - Exercise is essential for managing type 2 diabetes, however approximately only
      40% of people with the condition meet guidelines. The aim of this review is to
      examine the evidence regarding the use self-report measures of affect to
      understand and predict exercise adherence. Self-reported affect has been
      successfully used to regulate exercise intensity, monitor training load, prevent
      injury, and predict future physical activity participation in otherwise healthy
      and some clinical populations. Specific recommendations are provided for research
      to explore the utility of self-report measures of affect to promote exercise
      adherence in people with type 2 diabetes.

PMID- 30117399
TI  - Hypertension, diabetes and neurodegenerative diseases: is there a clinical link
      through the Ca2+/cAMP signalling interaction?
AB  - BACKGROUND: Hypertension, diabetes and neurodegenerative diseases are among the
      most prevalent medical problems around the world, costing millions of dollars to
      the medical health systems. Indeed, hypertension has been associated with higher
      risk for decline of cognition, as evidenced in patients with Alzheimer's disease
      (AD). Furthermore, there is a clear relationship between hypertension and
      diabetes, reflecting substantial overlap in their etiology. Calcium (Ca2+)
      channel blockers (CCBs) have been classically prescribed for treating
      hypertension because of their mechanism of action due to reducing the influx of
      Ca2+ into the smooth muscles cells. In addition, many clinical and experimental
      studies have been demonstrating pleiotropic effects for CCBs. For instance, in
      hypertensive patients treated with CCBs, it can be observed lower incidence of
      neurodegenerative diseases such as AD. The virtual mechanism of action could be
      attributed to a restoration and maintenance of Ca2+ homeostasis, which is
      dysregulated in the neurodegenerative diseases, including also a reduction of
      neuronal apoptosis as part of these CCBs pleiotropic effects. Similarly, in
      hypertensive patients treated with CCBs, it can be observed an improvement of
      diabetes status such as glycemic control. A possible mechanism of action under
      debate could be attributed to a restoration of insulin secretion, then achieving
      glycemic control, and reduction of pancreatic beta-cell apoptosis. CONCLUSION:
      Considering the discovery of our group entitled "calcium paradox" due to
      Ca2+/cAMP signalling interaction, in this review I discussed the virtual
      involvement of this interaction in the pleiotropic effects of CCBs, including the
      possible role of the Ca2+/cAMP signalling interaction in the association between
      hypertension and higher risk for the decline of cognition, and diabetes.

PMID- 30117400
TI  - Prevention of Infection in Adults Receiving Intravenous Antibiotic Treatment via
      Indwelling Central Venous Access Devices.
AB  - Background The use of indwelling central venous access devices (CVADs) is
      associated with the development of bloodstream infections. When CVADs are used to
      administer systemic antibiotics, particularly second- or higher-generation
      cephalosporins, there is a particular risk of developing Clostridium difficile
      infection. The overall bloodstream infection rate is estimated to be around 1.74
      per 1000 central venous catheter (CVC)-days. Objective We hypothesised that daily
      oral administration of the anion-binding resin colestyramine (cholestyramine)
      would help prevent infections in those receiving intravenous antibiotic treatment
      via CVADs. Method A small case series is described of adult patients who received
      regular intravenous antibiotic treatment (ceftriaxone, daptomycin or vancomycin)
      for up to 40 weeks via indwelling CVADs; this represented a total of 357 CVC
      days. In addition to following well established strategies to prevent C.
      difficile infection, during the course of the intravenous antibiotic treatment
      the patients also received daily oral supplementation with 4 g colestyramine.
      Results There were no untoward infectious events. In particular, none of the
      patients developed any symptoms or signs of C. difficile infection, whereas
      approximately one case of a bloodstream infection would have been expected.
      Conclusion It is suggested that oral colestyramine supplementation may help
      prevent such infection through its ability to bind C. difficile toxin A (TcdA)
      and C. difficile toxin B (TcdB); these toxins are able to gain entry into host
      cells through receptor-mediated endocytosis, while anti-toxin antibody responses
      to TcdA and TcdB have been shown to induce protection against C. difficile
      infection sequelae.

PMID- 30117401
TI  - Synthesis, in-vivo and in-vitro Anti-inflammatory Evaluation of some Novel
      Coumarin Derivatives.
AB  - The promising activity of coumarin derivatives as anti-inflammatory agents has
      motivated us to synthesize a new series of coumarin derivatives aiming to improve
      the anti-inflammatory activity and/or bioavailability. In the present work, the
      reaction between compound III and different aromatic acyl chloride had resulted
      in a series of ester derivatives 1-9. All synthesized new compounds 1-9 along
      with compound III as a parent compound and Celecoxib as a reference, were
      assessed for their anti-inflammatory activity both in-vivo and in-vitro using the
      formalin-induced hind paw edema method and inhibition of albumin denaturation and
      red blood cells (RBCs) membrane stabilization, respectively. All compounds showed
      an improved activity compared with the parent compound III, in both in-vivo and
      in-vitro screening. In addition, compounds, 1, 5, 6, 7 and 8 showed significant
      anti-inflammatory activity compared with the standard compound Celecoxib with
      compound 6 has a comparable activity with Celecoxib in both in-vivo and in-vitro
      evaluation.

PMID- 30117403
TI  - Anti-Saccharomyces cerevisiae as Unusual Antibody in Autoimmune Polyglandular
      Syndrome Type III: A Case Report.
AB  - : Backgraund and Objective: Anti-Saccharomyces Cerevisiae Antibodies (ASCA) that
      are considered to reflect immune response against increased intestinal
      permeability due to mucosal damage are among the serological markers of Crohn's
      Disease. METHODS: However, this microbial seromarker was recently shown to be
      elevated in several autoimmune disorders such as celiac disease, autoimmune liver
      diseases, type 1 diabetes, and Graves' disease. Despite that fact, ASCA
      seropositivity in autoimmune polyglandular syndrome (APS) have never been
      reported before. RESULTS: Herein we present a 46-year-old woman who has uveitis,
      autoimmune thyroiditis, and primary ovarian failure. CONCLUSION: Based on the
      coexistence of these diseases, the patient was diagnosed with APS type III.
      Moreover, ASCA seropositivity was detected although she has no overt intestinal
      disease.

PMID- 30117402
TI  - Human Suicide Risk and Treatment Study.
AB  - INTRODUCTION: Suicide is still a major event of human mortality worldwide. Yet
      human suicide prediction, prevention and therapeutic systems at this moment are
      generally ineffective in the clinic. No diagnostic system is reliable for
      significantly suicidal prevention and mortality reduction. As a result, human
      suicide etiopathologic investigation (especially at genetic/molecular levels in
      the clinical settings) is quite necessary. In order to boost human suicide
      researches, emerging human suicide diagnostic/treatment study will be transformed
      from clinical symptom observations into new generations of candidate drug targets
      and therapeutics. To achieve this goal, associations between suicidal
      etiopathologic identification, genetic/bioinformatics-based diagnostics and
      putative drug targets must be exploited than ever before. After all, the
      interaction and relationships between environmental/genetic/molecular clues and
      overall patient's risk prediction (environmental influences and different
      therapeutic targets/types) should be found out. CONCLUSION: In the future,
      effective clinical suicide prediction, prevention and therapeutic systems can be
      established via scientific expeditions and causality discovery.

PMID- 30117404
TI  - Discover Patent Landscape of Two-photon Polymerization Technology for the
      Production of 3D Nano-structure Using Claim-based Approach.
AB  - Nanotechnology, like 3D printing, is one of the richest fields in research and
      progress in the past few years. Two Photon Polymerization (TPP) technology allows
      the 3D printing of nanoscale objects, so the nanoscale additive manufacturing has
      been no longer the thing in the future. This research investigates related US
      patent documents through the claim-based approach. By virtue of systematic
      analysis of the claims of patent documents, we can explicitly define technical
      features of patent document and the accurate patent classification, monitor the
      direction of enterprises' patent application portfolio and effectively grasp the
      trend of technological development of important manufacturers related to this
      technology. Also, we can thoroughly understand the feasible emerging technology
      and opportunities for market application for enterprises in technological
      development and strategic planning. The result shows 3M Company possesses
      numerous patent portfolios that base on the diversified innovative applications
      of TPP technology. Nanoscribe Company has a long-term advantage in monopolizing
      this technology. TPP-3DP technology has broad application prospects, of which the
      hydrogel material applied in tissue engineering and drug delivery is the future
      trend. Highly-initiated watersoluble initiators are particularly needed to
      increase its resolution and will be the direction of emerging technology in this
      domain.

PMID- 30117405
TI  - In Vitro Drug-Drug Interaction Potential of Sulfoxide and/or Sulfone Metabolites
      of Albendazole, Triclabendazole, Aldicarb, Methiocarb, Montelukast and
      Ziprasidone.
AB  - BACKGROUND: The use of poly-pharmacy in the present day clinical therapy has made
      identification of clinical drug-drug interaction risk an important aspect of drug
      development process. Although many drugs can be metabolized to sulfoxide and/or
      sulfone metabolites, seldom is known on the CYP inhibition potential and/or the
      metabolic fate for such metabolites. OBJECTIVE: The key objectives were: a) to
      evaluate the in vitro CYP inhibition potential of select parent drugs with
      sulfoxide/sulfone metabolites; b) to assess the in vitro metabolic fate of the
      same panel of parent drugs and metabolites. METHODS: In vitro drug-drug
      interaction potential of test compounds was investigated in two stages; 1)
      assessment of CYP450 inhibition potential of test compounds using human liver
      microsomes (HLM); and 2) assessment of test compounds as substrate of Phase I
      enzymes; including CYP450, FMO, AO and MAO using HLM, recombinant human CYP
      enzymes (rhCYP), human liver cytosol (HLC) and human liver mitochondrial (HLMit).
      All samples were analysed by LC-MS-MS method. RESULTS: CYP1A2 was inhibited by
      methiocarb, triclabendazole, triclabendazole sulfoxide, and ziprasidone sulfone
      with IC50 of 0.71 uM, 1.07 uM, 4.19 uM, and 17.14 uM, respectively. CYP2C8 was
      inhibited by montelukast, montelukast sulfoxide, montelukast sulfone,
      tribendazole, triclabendazole sulfoxide, and triclabendazole sulfone with IC50 of
      0.08 uM, 0.05 uM, 0.02 uM, 3.31 uM, 8.95 uM, and 1.05 uM, respectively. CYP2C9
      was inhibited by triclabendazole, triclabendazole sulfoxide, triclabendazole
      sulfone, montelukast, montelukast sulfoxide and montelukast sulfone with IC50 of
      1.17 uM, 1.95 uM, 0.69 uM, 1.34 uM, 3.61 uM and 2.15 uM, respectively. CYP2C19
      was inhibited by triclabendazole and triclabendazole sulfoxide with IC50 of 0.25
      and 0.22, respectively. CYP3A4 was inhibited by montelukast sulfoxide and
      triclabendazole with IC50 of 9.33 and 15.11, respectively. Amongst the studied
      sulfoxide/sulfone substrate, the propensity of involvement of CY2C9 and CYP3A4
      enzyme was high (approximately 56% of total) in the metabolic fate experiments.
      CONCLUSIONS: Based on the findings, a proper risk assessment strategy needs to be
      factored (i.e., perpetrator and/or victim drug) to overcome any imminent risk of
      potential clinical drug-drug interaction when sulfoxide/sulfone metabolite(s)
      generating drugs are coadministered in therapy.

PMID- 30117407
TI  - Description of a new species of rhinebothriidean tapeworm from the skate Dipturus
      batis in the Mediterranean Sea.
AB  - Examination of rajid skates off the Algerian coast in the Mediterranean Sea
      revealed that three of the 33 Dipturus batis Linnaeus, 1758 examined harboured a
      new tapeworm species: Echeneibothrium algeriensis n. sp. This new species,
      collected from the anterior half of the spiral valves, is described on the basis
      of morphological data from light and scanning electron microscopy. The new
      species differs from previously described Echeneibothrium species by details of
      the scolex and loculi, total length, the length of the myzorhynchus, the number
      of proglottides, and the number of testes. Comparison of the diets of the ten
      skate species common in the Mediterranean basin indicates some varying degree of
      overlap, suggesting that host specificity in this host-parasite system is
      determined by other host and/or ecological variables such as adaptations of the
      parasites to their respective hosts, either on the morpho-anatomical level, in
      physiological characteristics of the parasite's habitat, in the trophic
      requirements for the successful transmission of the parasite, or in adaptations
      to the behavioural characteristics of the host. Furthermore, restricted overlap
      of E. algeriensis n. sp. with congeners in parasite assemblages of D. batis
      indicates some structuring according to attachment-site preferences. However,
      attachment-site preferences are not explained solely by morphological
      compatibility between bothridia and villi. This study reiterates the need to
      examine multiple factors synergistically in studies on host specificity of
      parasites, and the need to examine the parasite fauna of hosts across their
      entire geographical range in order to truly appreciate the biodiversity they
      harbour.

PMID- 30117406
TI  - Choline-PET/CT in the differential diagnosis between cystic glioblastoma and
      intraparenchymal hemorrhage.
AB  - OBJECTIVE: Glioblastoma multiforme (GBM) represents the most common and malignant
      glioma, accounting for 45%-50% of all gliomas . The median survival time for
      patients with glioblastoma is only 12-15 months after surgical, chemioterapic and
      radiotherapic treatment; a correct diagnosis is naturally fundamental to
      establish a rapid and correct therapy. Non-invasive imaging plays a pivotal role
      in each phase of the diagnostic workup of patients with suspected for diagnosis.
      The aim of this case report was to describe the potential clinical impact of 18F
      fluorocholine (FCH) PET/CT in the assessment of a cystic GBM mimicking a
      spontaneous hemorrhage. METHODS: a 57 years-old male with intraparenchymal
      hemorrhage at CT imaging initially in reduction ad serial imaging and suspected
      right fronto-temporo-parietal lesion at MRI underwent to dynamic and static (60'
      after tracer injection) FCH PET/CT of the brain. RESULTS: FCH PET/CT showed rapid
      tracer uptake after few second from injection at dynamic acquisition and
      consequent incremental mild uptake at static imaging after 60 minute at the level
      of oval formation in the right cerebral hemisphere characterized by annular and
      peripheral high metabolic activity. The central region of the lesion was
      characterized by absent 18F-FCH uptake most likely due to blood component. he
      patient underwent surgery for tumor removal; the histopathological examination
      confirmed the suspect of GBM. Chemo-radiotherapic adjuvant protocol according to
      Stupp protocol was therefore administrated; to date the patient is alive without
      any progression disease at 5 months from treatment. CONCLUSION: in this case
      report FCH PET/CT represented the final diagnostic technique to confirm the
      suspicious of a cystic GBM. Our case demonstrated the potential role of 18F-FCH
      PET/CT for discrimination of higher proliferation area over intraparenchymal
      hemorrage, supporting the potential use of this imaging biomarker in surgical or
      radiosurgical approach. Obviously, further prospective studies are needed to
      confirm this role and to exactly define possible routinely applications.

PMID- 30117409
TI  - The Dark Side of the (Preparedness) Moon: Why Promoting Public Preparedness
      Remains Challenging.
AB  - Despite best intentions and considerable effort, promoting households'
      preparedness to emergencies remains insufficiently low globally. It seems that,
      in some cases, particularly those in which populations are frequently exposed to
      any given threat, a more complex sociopsychological framework emerges - one in
      which classical motivators, such as threat perception cues, are no longer capable
      of turning salient belief into action. Recent studies suggest that this
      phenomenon, called victimization, has considerable implications on the efficacy
      of risk communication efforts and could jeopardize the success in promoting
      public readiness. Circumventing the psychological barriers caused by this
      phenomenon requires innovative approaches, such as using external incentives. The
      model and its implications are discussed (Disaster Med Public Health Prep.
      2017;page 1 of 3).

PMID- 30117408
TI  - Non-contrast magnetic resonance imaging for monitoring patients with acoustic
      neuroma.
AB  - OBJECTIVE: To assess the feasibility of non-contrast T2-weighted magnetic
      resonance imaging as compared to T1-weighted post-contrast magnetic resonance
      imaging for detecting acoustic neuroma growth. METHODS: Adult patients with
      acoustic neuroma who underwent at least three magnetic resonance imaging scans of
      the internal auditory canals with and without contrast in the past nine years
      were identified. T1- and T2-weighted images were reviewed by three
      neuroradiologists, and tumour size was measured. Accuracy of the measurements on
      T2-weighted images was defined as a difference of less than or equal to 2 mm from
      the measurement on T1-weighted images. RESULTS: A total of 107 magnetic resonance
      imaging scans of 26 patients were reviewed. Measurements on T2-weighted magnetic
      resonance imaging scans were 88 per cent accurate. Measurements on T2-weighted
      images differed from measurements on T1-weighted images by an average of 1.27 mm,
      or 10.4 per cent of the total size. The specificity of T2-weighted images was
      88.2 per cent and the sensitivity was 77.8 per cent. CONCLUSION: The T2-weighted
      sequences are fairly accurate in measuring acoustic neuroma size and identifying
      growth if one keeps in mind the caveats associated with the tumour
      characteristics or location.

PMID- 30117410
TI  - Short- and long-term effects of conventional and artificial rearing strategies on
      the health and performance of growing lambs.
AB  - Artificial rearing of young animals represents a challenge in modern ruminant
      production systems. This work aims to evaluate the short- and long-term effects
      of the type of rearing on the animal's health, growth, feed utilization and
      carcass performance. A total of 24 pregnant ewes carrying triplets were used.
      Within each triplet set, lambs were randomly allocated to one experimental
      treatment: natural rearing on the ewe (NN); ewe colostrum for 24 h followed by
      artificial rearing with milk replacer (NA) and 50 g of colostrum alternative
      supplementation followed by artificial rearing (AA). Milk replacer, ryegrass hay
      and creep feed were offered ad libitum, and each experimental group was kept in
      independent pens until weaning at 45 days of age. After weaning all lambs were
      placed together on the same pasture for fattening for 4 months. Blood samples
      were taken at 24 h after birth, at weaning and at the end of the fattening period
      (23 weeks). Results showed that no failure in the passive immune transfer was
      detected across treatments. Although artificially reared lambs at weaning had
      lower plasma levels of beta-hydroxy-butyrate (-62%), high-density lipoproteins (
      13%) and amylase (-25%), and higher levels of low-density lipoproteins (+38%) and
      alkaline phosphatase (+30%), these differences disappeared during the fattening
      period. Only the greater levels of calcium and the lower levels of haemoglobin
      and white blood cells detected at weaning in artificially reared lambs (+7.2%, 
      2.8% and -17.8%) persisted by the end of the fattening period (+4.3%, -3.3% and 
      9.5%, respectively). Minor diarrheal events from weeks 2 to 5 were recorded with
      artificial rearing, leading to lower growth rates during the 1st month. However,
      these artificially reared lambs caught up towards the end of the milk feeding
      period and reached similar weaning weights to NN lambs. During the fattening
      period NN lambs had a greater growth rate (+16%) possibly as a result of their
      greater early rumen development, which allowed a higher feed digestibility during
      the fattening period in comparison to NA lambs (+5.9%). As a result, NN lambs had
      heavier final BWs (+7.0%), but tended to have lower dressing percentage (-5.7%)
      than artificially reared lambs, thus no differences were noted in either carcass
      weight or in carcass conformation across treatments. In conclusion, the use of a
      colostrum alternative and milk replacer facilitated the successful rearing of
      lambs, reaching similar productive parameters; however, special care must be
      taken to maximize the rumen development before weaning.

PMID- 30117411
TI  - Molecular mechanisms of lipid metabolism disorder in livers of ewes with
      pregnancy toxemia.
AB  - Pathogenesis of pregnancy toxemia (PT) is believed to be associated with the
      disruption of lipid metabolism. The present study aimed to explore the underlying
      mechanisms of lipid metabolism disorder in the livers of ewes with PT. In total,
      10 pregnant ewes were fed normally (control group) whereas another 10 were
      subjected to 70% level feed restriction for 15 days to establish a pathological
      model of PT. Results showed that, as compared with the controls, the levels of
      blood beta-hydroxybutyrate (BHBA), non-esterified fatty acids (NEFAs) and
      cholesterol were greater (P<0.05) and blood glucose level was lower (P<0.05) in
      PT ewes. The contents of NEFAs, BHBA, cholesterol and triglyceride were higher
      (P<0.05) and glycerol content was lower (P<0.05) in hepatic tissues of PT ewes
      than those of the controls. For ewes with PT, excessive fat vacuoles were
      observed in liver sections stained with hematoxylin-eosin; furthermore, inner
      structures of hepatocytes including nuclei, mitochondria and endoplasmic
      reticulum were damaged seriously according to the results of transmission
      electron microscope. Real-time PCR data showed that compared with the controls,
      the expression of hepatic genes involved in fatty acid oxidation (FAO) and
      triglyceride synthesis (TGS) was enhanced (P<0.05) whereas that related to acetyl
      CoA metabolism (ACM) was repressed (P<0.05) in PT ewes. Generally, our results
      showed that negative energy balance altered the expression of genes involved in
      FAO, ACM and TGS, further caused lipid metabolism disorder in livers, resulting
      in PT of ewes. Our findings may provide the molecular basis for novel therapeutic
      strategies against this systemic metabolic disease in sheep.

PMID- 30117412
TI  - Dietary L-arginine supplementation increased mammary gland vascularity of
      lactating sows.
AB  - The present study aimed to evaluate the mechanisms modulated by dietary arginine
      supplementation to sows during lactation regarding antioxidant capacity and
      vascularization of mammary glands. At 109 days of gestation, animals were
      transferred to individual farrowing crates equipped with manual feeders and
      automatic drinker bowls. Environmental temperature and humidity inside the
      farrowing rooms were registered every 15 min. At farrowing, sows were assigned in
      a completely randomized design to a control diet (CON) or the CON diet
      supplemented with 1.0% L-arginine (ARG). A total of three gilts and two sows were
      fed the CON diet, whereas three gilts and three sows were fed ARG diets. Sows
      were fed a fixed amount of 6.0 kg/day, subdivided equally in four delivery times
      (0700, 1000, 1300 and 1600 h) for 21 days. At weaning, sows were slaughtered and
      mammary tissue samples and blood from the pudendal vein were collected. Data were
      analyzed considering each sow as an experimental unit. Differences were
      considered at P<0.05. L-arginine fed sows presented lower messenger RNA (mRNA)
      expression for prolactin receptor (P=0.002), angiopoietin1 (P=0.03) and receptor
      tyrosine kinase (P=0.01); higher mRNA expression for prostaglandin synthase 1
      (P=0.01); a trend of decrease for glucocorticoid receptor (P=0.06) and IGF
      receptor 1 (P=0.07); and a trend (P=0.05) for an increased glutathione peroxidase
      mRNA expression. The angiopoietin2:angiopoietin1 mRNA ratio tended to increase
      (P=0.07) in ARG fed sows. L-arginine fed sows had greater (P=0.04) volumetric
      proportion of blood vessels and a trend of enhance (P=0.07) in the number of
      blood vessels per mm2. These findings show that 1.0% ARG supplementation to sows
      activates proliferative mechanisms, may improve mammary tissues' angiogenesis and
      tended to increase mRNA expression of genes that encode antioxidant enzymes in
      mammary gland of sows.

PMID- 30117413
TI  - Mean difference in live-weight per incremental difference in body condition score
      estimated in multiple sheep breeds and crossbreds.
AB  - Body condition score (BCS) is a subjective assessment of the proportion of body
      fat an animal possesses and is independent of frame size. There is a growing
      awareness of the importance of mature animal live-weight given its contribution
      to the overall costs of production of a sector. Because of the known relationship
      between BCS and live-weight, strategies to reduce live-weight could contribute to
      the favouring of animals with lesser body condition. The objective of the present
      study was to estimate the average difference in live-weight per incremental
      change in BCS, measured subjectively on a scale of 1 to 5. The data used
      consisted of 19 033 BCS and live-weight observations recorded on the same day
      from 7556 ewes on commercial and research flocks; the breeds represented included
      purebred Belclare (540 ewes), Charollais (1484 ewes), Suffolk (885 ewes), Texel
      (1695 ewes), Vendeen (140 ewes), as well as, crossbreds (2812 ewes). All
      associations were quantified using linear mixed models with the dependent
      variable of live-weight; ewe parity was included as a random effect. The
      independent variables were BCS, breed (n=6), stage of the inter-lambing interval
      (n=6; pregnancy, lambing, pre-weaning, at weaning, post-weaning and mating) and
      parity (1, 2, 3, 4 and 5+). In addition, two-way interactions were used to
      investigate whether the association between BCS and live-weight differed by
      parity, a period of the inter-lambing interval or breed. The association between
      BCS and live-weight differed by parity, by a period of the inter-lambing interval
      and by breed. Across all data, a one-unit difference in BCS was associated with
      4.82 (SE=0.08) kg live-weight, but this differed by parity from 4.23 kg in parity
      1 ewes to 5.82 kg in parity 5+ ewes. The correlation between BCS and live-weight
      across all data was 0.48 (0.47 when adjusted for nuisance factors in the
      statistical model), but this varied from 0.48 to 0.53 by parity, from 0.36 to
      0.63 by stage of the inter-lambing interval and from 0.41 to 0.62 by breed.
      Results demonstrate that consideration should be taken of differences in BCS when
      comparing ewes on live-weight as differences in BCS contribute quite
      substantially to differences in live-weight; moreover, adjustments for
      differences in BCS should consider the population stratum, especially breed.

PMID- 30117417
TI  - [Research progress in the mechanism of translation initiation of eukaryotic
      mRNAs].
AB  - The translation of mRNA is a complicated multi-step process, including
      initiation, elongation and termination. Among them, the regulation of the initial
      stage plays the key role. There are many ways to initiate mRNA translation, and
      the most classical way is the m 7G cap-dependent scanning mechanism that was also
      the first mechanism identified. When cells encounter adversity and the classical
      mechanism is inhibited, other types of translation initiation mechanisms will be
      activated. In this review, we summarize the translation initiation mechanisms of
      eukaryotic mRNAs, especially some alternative mechanisms. It will provide a
      reference for further understanding of the expression and regulation of
      eukaryotic genes at the translation levels.

PMID- 30117415
TI  - Trade-off shapes diversity in eco-evolutionary dynamics.
AB  - We introduce an Interaction- and Trade-off-based Eco-Evolutionary Model (ITEEM),
      in which species are competing in a well-mixed system, and their evolution in
      interaction trait space is subject to a life-history trade-off between
      replication rate and competitive ability. We demonstrate that the shape of the
      trade-off has a fundamental impact on eco-evolutionary dynamics, as it imposes
      four phases of diversity, including a sharp phase transition. Despite its
      minimalism, ITEEM produces a remarkable range of patterns of eco-evolutionary
      dynamics that are observed in experimental and natural systems. Most notably we
      find self-organization towards structured communities with high and sustained
      diversity, in which competing species form interaction cycles similar to rock
      paper-scissors games.

PMID- 30117418
TI  - [Comparison of different single cell whole genome amplification methods and
      MALBAC applications in assisted reproduction].
AB  - Single-cell whole genome amplification (WGA) is a new technology, which can
      amplify small amounts of DNA from single cell and obtain the high coverage whole
      genome DNA template for revealing cell heterogeneity. Single cell WGA methods
      mainly include primer extension preamplification PCR (PEP-PCR), degenerate
      oligonucleotide primed PCR (DOP-PCR), multiple displacement amplification (MDA),
      and multiple annealing and looping-based amplification cycles (MALBAC). In this
      review, we describe the principles and applications of different single cell
      genome wide amplification, and we evaluate and compare their amplification
      efficiency, including the coverage of genome, homogeneity, reproducibility, and
      detection power of single-nucleotide variants (SNV) and copy number variants
      (CNV). The results show that MALBAC have the highest amplification homogeneity,
      the lowest allelic gene knockdown rate, the best reproducibility, and the best
      detection effect on CNV and SNV. We also describe the applications of MALBAC in
      human single sperm meiosis, aneuploidy analysis, and human oocyte genome
      research.

PMID- 30117419
TI  - [Progress and application of genome-edited pigs in biomedical research].
AB  - Genome editing technologies (GETs) can precisely alter the genomic sequences and
      modify the genetic information at the target site of an organism. Since the
      beginning of the 21st century, the GETs, including zinc finger nucleases (ZFN),
      transcription-activating-like receptor factor (TALEN), and clustered regularly
      interspaced short palindromic repeats/Cas endonucleases (CRISPR/Cas), have been
      successively developed. The GETs can easily engineer the targeted genomic site of
      animals to exhibit a desired phenotype(s), thereby providing valuable tools in
      biomedical research. The pigs are closely related to human, in terms of
      similarities in physiological properties and pathogenic characters. Thus, pigs
      have been used as important animal models in studies of human disease,
      xenotransplantation, and humanized organs regeneration. In this review, we
      summarize the development of the three GETs, research progress of genome-edited
      pigs as disease models and organ donors for xenotransplantation, and the
      prospects of their applications in future biomedical research.

PMID- 30117416
TI  - Ssd1 and Gcn2 suppress global translation efficiency in replicatively aged yeast
      while their activation extends lifespan.
AB  - Translational efficiency correlates with longevity, yet its role in lifespan
      determination remains unclear. Using ribosome profiling, translation efficiency
      is globally reduced during replicative aging in budding yeast by at least two
      mechanisms: Firstly, Ssd1 is induced during aging, sequestering mRNAs to P
      bodies. Furthermore, Ssd1 overexpression in young cells reduced translation and
      extended lifespan, while loss of Ssd1 reduced the translational deficit of old
      cells and shortened lifespan. Secondly, phosphorylation of eIF2alpha, mediated by
      the stress kinase Gcn2, was elevated in old cells, contributing to the global
      reduction in translation without detectable induction of the downstream Gcn4
      transcriptional activator. tRNA overexpression activated Gcn2 in young cells and
      extended lifespan in a manner dependent on Gcn4. Moreover, overexpression of Gcn4
      sufficed to extend lifespan in an autophagy-dependent manner in the absence of
      changes in global translation, indicating that Gcn4-mediated autophagy induction
      is the ultimate downstream target of activated Gcn2, to extend lifespan.

PMID- 30117414
TI  - Staphylococcal Biofilms.
AB  - Staphylococci, with the leading species Staphylococcus aureus and Staphylococcus
      epidermidis, are the most frequent causes of infections on indwelling medical
      devices. The biofilm phenotype that those bacteria adopt during device-associated
      infection facilitates increased resistance to antibiotics and host immune
      defenses. This review presents and discusses the molecular mechanisms
      contributing to staphylococcal biofilm development and their in-vivo importance.
      Furthermore, it summarizes current strategies for the development of therapeutics
      against staphylococcal biofilm-associated infection.

PMID- 30117420
TI  - [Exploration and characterization of a universal piggyBac transposon vector for
      efficient transgene studies in sheep].
AB  - piggyBac (PB) is a DNA transposon that mediates transposition in various animal
      cells. As an efficient tool, PB transposons are applied to various transgenic
      research and optimized for different species, which is an essential means to
      enhance its versatility. To construct a universal PB transposase (PBase) vector
      for ovine transgene manipulation, the gene expression box of PBase with optimized
      bias for sheep codons was inserted into the pBNW-TP1 vector. The vector pBNW-TP2
      with a single plasmid was successfully constructed. Then, pBNW-TP2 was
      transfected into ovine fibroblasts and mammary epithelial cells. The stable
      transfected cell lines were selected by G418 and the PB transposition sites were
      determined by Tail-PCR in the stable transfected cell lines. The transposition
      efficiency was verified by student's t-tests for cell clones with methylene blue
      staining. The results showed that pBNW-TP2 successfully guided the production of
      transgenic ovine fibroblasts and mammary epithelial cell lines. The PB
      transposition test indicated that the pBNW-TP2 vector can be specifically
      integrated into the TTAA sites of the sheep genome. The statistical analysis of
      methylene blue staining results suggested that the transgenic efficiency mediated
      by the pBNW-TP2 vector increased significantly. In summary, we verified and
      analyzed characteristics of the universal PB transposon vector pBNW-TP2 for sheep
      in this study, which will provide a scientific basis for future transgenic
      research mediated by the PB transposon in ovine somatic cells.

PMID- 30117421
TI  - [Post-transcriptional regulation of chicken PPARgamma transcript variant 3 by
      upstream open reading frame].
AB  - Peroxisome proliferator-activated receptor gamma (PPARgamma) is a critical
      regulator of adipogenesis. Our previous study showed that unlike human and mouse
      PPARgamma transcripts, several chicken PPARgamma transcript variants contain
      upstream open reading frames (uORFs) in their 5'untranslated region (5'TR). To
      decipher the role of uORFs in post-transcriptional regulation of chicken
      PPARgamma gene, we constructed wild-type (psiCHECK2-cPPARgamma3-5'UTR-WT) and a
      uORF mutant (the upstream ATG (uATG) was mutated to stop codon TGA) 5'UTR
      reporters (psiCHECK2-cPPARgamma3- 5'UTR-Mut) of chicken PPARgamma transcript
      variant 3 (cPPARgamma3). These two reporters were individually transfected into
      immortalized chicken pre-adipocytes (ICPA) and DF1 cells, and the renilla
      luciferase (hRluc) activity and mRNA expression level were detected by reporter
      assay and qRT-PCR. The results showed that the hRluc activity of the mutated
      5'UTR was significantly higher than that of the wild-type 5'UTR in ICPA cells
      (P<0.01), and the hRluc activity of the mutated 5'UTR tended to be higher than
      that of the wild-type 5'UTR in DF1 cells, but this difference did not reach
      statistical significance (P>0.05). The qRT-PCR analysis showed, in ICPA cells,
      the hRluc mRNA expression was significantly lower in the cells transfected with
      the mutated 5'UTR construct than in the cells transfected with the wild-type
      5'UTR construct (P<0.01). In DF1 cells, the hRluc mRNA expression tended to be
      lower in the cells transfected with the mutated 5'UTR construct than in the cells
      transfected with the wild-type 5'UTR construct, but this difference did not reach
      statistical significance (P>0.05). To further gain insight into the post
      transcriptional regulation of cPPARgamma3 by the uORF, we constructed the
      expression plasmids bearing the full-length coding region of chicken PPARgamma
      gene plus either wild-type or mutant uORF 5'UTR (pcDNA3.1-cPPARgamma3-WT and
      pcDNA3.1-cPPARgamma3-Mut). These two constructed PPARgamma expression plasmids
      were individually transiently transfected into both ICPA and DF1 cells, and
      PPARgamma mRNA and protein levels were assayed by qRT-PCR and western blotting.
      The result showed that in both cell lines, PPARgamma mRNA expression was
      significantly lower in the cells transfected with pcDNA3.1-cPPARgamma3-Mut than
      in the cells transfected with pcDNA3.1-cPPARgamma3-WT (P<0.05). In contrast,
      western blot analysis showed that PPARgamma protein level was significantly
      higher in the cells transfected with pcDNA3.1-cPPARgamma3-Mut than in the cells
      transfected with pcDNA3.1-cPPARgamma3-WT (P<0.001). Taken together, our results
      demonstrate that the uORF in 5'UTR of the cPPARgamma3 inhibits its translation.

PMID- 30117422
TI  - [Detection of UGT1A1*6 single nucleotide polymorphism in oral swap samples using
      the cascade invader assay-based real-time PCR].
AB  - The adverse reaction to irinotecan is related to the single nucleotide
      polymorphism (SNP) of UGT1A1*6 genotype. The current SNP detection methods have
      various disadvantages, including time-consuming procedures, high- risk cross
      contamination, and cumbersome operation. Hence, it is necessary to establish a
      new method suitable for clinical application, which is easy and simple to detect
      SNP with minimal risk for cross-contamination. In this study, a cascade invader
      assay-based real-time PCR, for UGT1A1*6 genotyping has been established by
      optimizing reaction conditions with DNA samples of three genotypes. The
      sensitivity and accuracy of the method were evaluated with DNAs derived from oral
      swab samples. The results showed that the method could detect the UGT1A1*6
      genotypes from the oral swab samples with a detection limit of 6 ng genomic DNA
      with 100% accuracy. Due to its convenient and non-invasive sampling, single close
      tube operation, and minimal risk for cross-contamination, the method has the
      potential in clinical application for individualized detection of drug-related
      UGT1A1*6 polymorphism and reaction to irinotecan.

PMID- 30117423
TI  - [Identifying T-DNA insertion site(s) of transgenic plants by whole-genome
      resequencing].
AB  - The availability of T-DNA insertion sites is very important for plant functional
      genomics research and the screening and identification of transgenic plants.
      However, the present protocols for identifying T-DNA insertion sites, like
      reverse PCR and semi-random primer PCR, are not only complex and time-consuming,
      but also inefficient. In this paper, a DNA pool of three transgenic plants was
      sequenced by whole-genome resequencing, and four T-DNA insertion sites were
      identified by blasting using transgenic T-DNA sequences. After PCR and Southern
      blot analysis, the T-DNA insertion sites of the three transgenic plants were
      successfully confirmed, and one of the transgenic plants showed two insertion
      sites. In conclusion, this study established a simple, reliable and efficient
      method for obtaining T-DNA insertion sites in transgenic plants.

PMID- 30117424
TI  - [Development of resources, technologies and services at the China Zebrafish
      Resource Center].
AB  - With the rapid growth of the Chinese zebrafish community, there is an increasing
      demand for various types of zebrafish-related resources and technologies. The
      China Zebrafish Resource Center (CZRC, web: http://zfish.cn) was established at
      the Institute of Hydrobiology (IHB), Chinese Academy of Sciences (CAS) in 2012.
      Till now, CZRC has built the largest zebrafish aquaculture unit in China,
      organized a resource bank containing more than 1200 zebrafish lines and more than
      10 000 frozen sperm samples, among which over 200 mutant and transgenic lines
      were generated by CZRC. CZRC has established several technical supporting
      platforms, such as the zebrafish husbandry and health control program of
      international standard, a high-efficient gene manipulation technology platform,
      and a stable and efficient sperm cryopreservation technology platform. The main
      task of CZRC is to provide different types of services to zebrafish investigators
      in China and worldwide, such as resource services (e.g. zebrafish lines),
      technical services (e.g. gene knockout) and transgenic services, consultancy
      services (e.g. zebrafish husbandry and health consultation), and conference
      services [e.g. holding regular technical training courses and biennale Chinese
      Zebrafish Principal Investigator Meeting (CZPM)]. After five years' development,
      CZRC is now recognized as one of the three major resource centers in the global
      zebrafish community.

PMID- 30117425
TI  - [On the stigma of schizophrenia].
AB  - The paper provides a literature overview about the phenomena of stigma closely
      linked to mental illness as well as schizophrenia in particular. Describes the
      common roots and evolution of current professional scientific concept of "mental
      illness" and its impact on non-professional, everyday conceptualization as well
      as its linkage to possible stigmatization. Introduces research concepts of stigma
      and connected phenomena (perceived stigma, public stigma, self-stigma, prejudice,
      discrimination), clarifying their nature of relation and explanatory models.
      Describes the content of schizophrenia stigma and its harmful effects based on
      research, drawing attention to the need of starting comprehensive national
      research and to the importance of minimizing stigmatization.

PMID- 30117426
TI  - [Fear appealing health communication and coping style].
AB  - INTRODUCTION: The purpose of the reported study was to investigate how people
      respond to social advertisements which differ in topic and in the extent of fear
      appeal given their typical coping strategy. This is a topical issue as it has
      practical relevance to the design of persuasive communication in the service of
      health behavior, based on the relation between persuasion and personality. For a
      theoretical frame we used two cognitive evaluating models: Kim Witte's Extended
      Parallel Process Model and Endler and Parker's conception about different coping
      styles. METHOD: Online questionnaire was applied in the study. The sample
      consisted of 140 young adults. Every respondent perceived two fear appealing
      social advertisements and filled out Witte, McKeon, Cameron and Berkowitz' Risk
      Behavior Diagnosis Scale to assess health communications. Finally, they answered
      the items of Coping Inventory for Stressful Situations by Endler and Parker.
      RESULTS: Based on the results of the applied repeated measures ANOVA, we found
      that the link between coping mechanism and responses of adverts is neither
      linear, nor is general. CONCLUSIONS: A general consequence cannot be drawn
      regarding the relationship of constructs, but it seems that the relationship
      between the typical coping strategy and the reaction to the advertisements
      moderated or mediated by the presented topic of fear appealing messages.

PMID- 30117427
TI  - [Age-related and gender differences in conslidation of implicit sequence learning
      between 7 and 29 years of age].
AB  - INTRODUCTION: Extracting and acquiring sequential regularities from the
      environment is a fundamental human ability that underlies the acquisition of
      various motor, social and cognitive skills. As psychiatric rehabilitation often
      depends on the integrity of these skills, it is crucial to understand individual
      differences in sequence learning. Here we aimed to test age- and gender-related
      differences in sequence learning as well as in the consolidation of the acquired
      knowledge. METHODS: In the present study we aimed to characterize age-related and
      gender differences in the consolidation of implicitly acquired sequential
      memories between 7 and 29 years of age (N = 261). Participants were clustered
      into six age groups. The Alternating Serial Reaction Time (ASRT) task was used to
      measure implicit sequence learning. Participants were retested 24 hours after the
      learning phase. RESULTS: In the learning phase, implicit sequence learning showed
      a gradually declining pattern across age groups with children exhibiting the best
      learning performance, which is consistent with previous studies. Regarding
      consolidation, we found retention of implicit sequential memories in all age
      groups, with no age-related differences. We found no gender differences in the
      acquisition of sequential memories but gender differences emerged after the
      consolidation: male participants showed somewhat better performance in terms of
      accuracy compared to the female participants. CONCLUSION: Our study explores
      implicit sequence learning and consolidation in a relatively wide age range and
      can contribute to the development and testing of alternative methods in age
      specific psychiatric rehabilitation.

PMID- 30117428
TI  - [A short overview on the changes of the content of delusions - the impact of
      technological innovations, historical events and culture].
AB  - The content aspect of delusions has been going through fast and great changes
      over the past hundred years. In this paper we would like to lead the reader
      through these changes with the brief overview of the related literature, thus
      giving a better understanding of the underlying causes. In recent years several
      studies have been published on the impact of technological and cultural changes
      in delusions, as opposed to the stability of delusional themes over longer
      periods of time, proved by long-term comparisons and comparative transcultural
      studies on delusions, allowing for only a certain degree of variability.

PMID- 30117429
TI  - [Experiences of a Extreme, absolutist expressions may be marker-specific to
      depressive or anxious states and suicide].
AB  - No abstract available.

PMID- 30117431
TI  - [Three neuralgic points of psychiatric services: suicide prevention, treatment of
      dementia and the care of homeless psychiatric patients].
AB  - No abstract available.

PMID- 30117430
TI  - [Child psychiatrist in Rwanda].
AB  - No abstract available.

PMID- 30117432
TI  - [Reflections on Attila Nemeth's "Three neuralgic points of psychiatric services:
      suicide prevention, treatment of dementia and the care of homeless psychiatric
      patients" article].
AB  - No abstract available.

PMID- 30117433
TI  - [Mentalizing and rehumanization].
AB  - No abstract available.

PMID- 30117434
TI  - SCOPE: signal compensation for low-rank plus sparse matrix decomposition for fast
      parameter mapping.
AB  - Magnetic resonance (MR) parameter mapping is useful for many clinical
      applications. However, its practical utility is limited by the long scan time. To
      address this problem, this paper developed a novel image reconstruction method
      for fast MR parameter mapping. The proposed method (SCOPE) used a low-rank plus
      sparse model to reconstruct the parameter-weighted images from highly
      undersampled acquisitions. A signal compensation strategy was introduced to
      promote low rankness along the parametric direction and thus improve the
      reconstruction accuracy. Specifically, compensation was performed by multiplying
      the original signal by the inversion of the mono-exponential decay at each voxel.
      The performance of SCOPE was evaluated via quantitative T 1rho mapping. The
      results of the simulation and in vivo experiments with acceleration factors from
      3 to 5 are shown. The performance of SCOPE was verified via comparisons with
      several low-rank and sparsity-based methods. The experimental results showed that
      the T 1rho maps obtained using SCOPE were more accurate than those obtained using
      competing methods and were comparable to the reference, even when the
      acceleration factor reached 5. SCOPE can greatly reduce the scan time of
      parameter mapping while still achieving high accuracy. This technique might
      therefore help facilitate fast MR parameter mapping in clinical use.

PMID- 30117435
TI  - Anomalous conductance quantization in the inter-band gap of a one-dimensional
      channel.
AB  - We report on a singular departure from the canonical step sequence of quantized
      conductance in a ballistic, quasi-one-dimensional metallic channel. Ideally in
      such a structure each sub-band population contributes its conductance quantum
      independently of the rest. In a picture based exclusively on coherent single
      carrier transmission, unitary back-scattering may lower a conductance step below
      ideal but it is not possible for it to enhance it beyond the ideal conductance
      quantum. Precisely such an anomalous and robust voltage-dependent enhancement has
      already been observed over the whole density range between sub-band thresholds
      (de Picciotto R et al 2004 Phys. Rev. Lett. 92 036805, de Picciotto R et al 2008
      J. Phys.: Condens. Matter 20 164204), a phenomenon left unexplained till now. We
      show theoretically that the anomalous enhancement of the ideal conductance is the
      hallmark of carrier transitions coupling the discrete sub-bands.

PMID- 30117436
TI  - Quantum vortex melting and superconductor insulator transition in a 2D Josephson
      junction array in a perpendicular magnetic field via diffusion Monte Carlo.
AB  - In this study, we simulated a quantum rotor model describing a Josephson junction
      array (JJA) in the phase representation at zero temperature in a perpendicular
      magnetic field [Formula: see text] (in units of [Formula: see text]) on a
      [Formula: see text] square lattice with spacing a for [Formula: see text]. The
      superconductor-insulator transition (SIT) is tuned by the ratio of charging
      energy to Josephson coupling, U/J. Abrupt drops in the magnetization values were
      observed in the bigger lattices at certain values of B and U/J caused by the
      formation of vortices. Increasing U/J at a fixed B field causes quantum vortex
      melting. The magnetization drops to zero around [Formula: see text] indicating
      SIT. For B  =  0.1 the SIT occurs without an intermediate vortex state and the
      magnetization scales as [Formula: see text], whereas for B  =  0.4 the scaling is
      [Formula: see text] during the vortex melting. For B between 0.1 and 0.4 the
      scaling is not clear. We used the diffusion Monte Carlo (DMC) method with a
      guiding wavefunction optimized using the variational Monte Carlo (VMC) method.
      The ground state energy is calculated easily in DMC and its error estimates were
      generally smaller than [Formula: see text], both with and without the guiding
      wavefunction. Quantities like magnetization and vorticity that do not commute
      with the Hamiltonian were calculated using an efficient forward walking
      algorithm. Their estimates are affected severely in absence of the guiding
      wavefunction. With the guiding wavefunction, errors for the magnetization were
      generally less than [Formula: see text] and going up to [Formula: see text]
      percent around the phase transition from the Meissner to the vortex state, and
      without the guiding wavefunction errors were generally higher than [Formula: see
      text] and going up to [Formula: see text] around the critical point.

PMID- 30117437
TI  - Single-shot Talbot-Lau x-ray dark-field imaging of a porcine lung applying the
      moire imaging approach.
AB  - Talbot-Lau x-ray imaging provides additionally to the conventional attenuation
      image, two further images: the differential phase-contrast image which is
      especially sensitive to differences in refractive properties and the dark-field
      image which is showing the x-ray scattering properties of the object. Thus, in
      the dark-field image sub-pixeled object information can be observed. As it has
      been shown in recent studies, this is of special interest for lung imaging.
      Changes in the alveoli structure, which are in the size of one detector pixel,
      can be seen in the dark-field images. A fast acquisition process is crucial to
      avoid motion artifacts due to heartbeat and breathing of the patient. Using moire
      imaging the images can be acquired with a single-shot exposure. Nevertheless, the
      spatial resolution is reduced compared to the phase-stepping acquisition. We
      evaluate the results of both imaging techniques towards their feasibility in
      clinical routine. Furthermore, we analyse the influence of artificial linear
      object movement on the image quality, in order to simulate the heartbeat of a
      patient.

PMID- 30117438
TI  - High-throughput assessment of vacancy formation and surface energies of materials
      using classical force-fields.
AB  - In this work, we present an open access database for surface and vacancy
      formation energies using classical force-fields (FFs). These quantities are
      essential in understanding diffusion behavior, nanoparticle formation and
      catalytic activities. FFs are often designed for a specific application, hence,
      this database allows the user to understand whether a FF is suitable for
      investigating particular defect and surface-related material properties. The FF
      results are compared to density functional theory and experimental data whenever
      applicable for validation. At present, we have 17 506 surface energies and 1000
      vacancy formation energies calculation in our database and the database is still
      growing. All the data generated, and the computational tools used, are shared
      publicly at the following websites: www.ctcms.nist.gov/~knc6/periodic.html,
      https://jarvis.nist.gov and https://github.com/usnistgov/jarvis. Approximations
      used during the high-throughput calculations are clearly mentioned. Using some of
      the example cases, we show how our data can be used to directly compare different
      FFs for a material and to interpret experimental findings such as using Wulff
      construction for predicting equilibrium shape of nanoparticles. Similarly, the
      vacancy formation energies data can be useful in understanding diffusion related
      properties.

PMID- 30117439
TI  - Evolving Paradigms of Personalized Medicine in Oncology.

PMID- 30117440
TI  - Mapping of health research funding in India.
AB  - Background.: We aimed to estimate the total annual funding available for health
      research in India. We also examined the trends of funding for health research
      since 2001 by major national and international agencies. Methods.: We did a
      retrospective survey of 1150 health research institutions in India to estimate
      the quantum of funding over 5 years. We explored the Prowess database for
      industry spending on health research and development and gathered data from key
      funding agencies. All amounts were converted to 2015 constant US$. Results.: The
      total health research funding available in India in 2011-12 was US$ 1.42 billion,
      0.09% of the gross domestic product (GDP) including only 0.02% from public
      sources. The average annual increase of funding over the previous 5 years (2007
      08 to 2011-12) was 8.8%. 95% of this funding was from Indian sources, including
      79% by the Indian pharmaceutical industry. Of the total funding, only 3.2% was
      available for public health research. From 2006-10 to 2011-15 the funding for
      health research in India by the three major international agencies cumulatively
      decreased by 40.8%. The non-industry funding for non-communicable diseases
      doubled from 2007-08 to 2011-12, but the funding for some of the leading causes
      of disease burden, including neonatal disorders, cardiovascular disease, chronic
      respiratory disease, mental health, musculoskeletal disorders and injuries was
      substantially lower than their contribution to the disease burden. Conclusion.:
      The total funding available for health research in India is lower than previous
      estimates, and only a miniscule proportion is available for public health
      research. The non industry funding for health research in India, which is
      predominantly from public resources, is extremely small, and had considerable
      mismatches with the major causes of disease burden. The magnitude of public
      funding for health research and its appropriate allocation should be addressed at
      the highest policy level.

PMID- 30117441
TI  - Status and trend of acute encephalitis syndrome and Japanese encephalitis in
      Bihar, India.
AB  - Background.: Acute encephalitis syndrome (AES) is a clinical condition, of which
      the most common cause is Japanese encephalitis (JE). Though there is deficiency
      of data on AES and JE from Bihar, the state ranks third in the reporting of JE
      cases after Uttar Pradesh and Assam. We aimed to assess the status and trends of
      AES and JE cases in Bihar and to know the status of the disease in the districts.
      Methods.: We collected monthly epidemiological data for AES and JE for the period
      2009-2014. Results.: A total of 4400 cases (733 cases/year) with an average case
      fatality rate (CFR) of 30% for AES for the entire study period. A total of 396
      cases of JE were reported with approximately 14% CFR. The disease peaks were
      during the start and end of the Indian summer and monsoon months for AES and JE,
      respectively. Districts such as Patna, Jehanabad, Nawada, Gaya and East Champaran
      reported the maximum number of AES and JE cases with annual incidence rates of
      4.7-25.0 and 0.546-1.78 per 100 000 population, respectively. Conclusion.: Since
      2009, the incidence of AES and JE cases has been increasing in Bihar.

PMID- 30117442
TI  - Terbinafine-induced liver injury.
AB  - Terbinafine is a common antifungal agent with few reports of liver injury. We
      present a 64-year-old man who developed terbinafine-induced liver injury. Drug
      induced liver injury is an important cause of morbidity and an early diagnosis
      may prevent progression to severe and chronic forms of liver injury including
      fulminant hepatic failure.

PMID- 30117443
TI  - Biological pacemakers: Concepts and techniques.
AB  - The sinoatrial (SA) node is the dominant pacemaker of the heart which initiates
      the process of impulse generation in the cardiac tissue, thereby defining the
      rate and rhythm of cardiac contraction. The automaticity of the conduction cells
      in the SA node is due to ion channels which are inter-linked by molecular,
      histological and electrophysiological mechanisms causing spontaneous diastolic
      depolarization and generation of an impulse. The SA nodal action potentials are
      then transmitted to the ventricles by electrical coupling of the myocytes in
      different areas of the heart. Regulatory pathways overseeing cardiac impulse
      generation and conduction provide effective and safe pacing, and help maintain
      the rate according to the physiological demands of the individual's body. Failure
      of physiological pacing due to any pathology in the SA or atrioventricular node
      necessitates implantation of a permanent pacemaker. Implantable pacemakers,
      despite technological advances, are not without practical limitations including a
      defined battery life leading to lead and/or generator replacement at periodic
      intervals, vascular complications, occasional component failure, electronic
      interference from external/ internal sources, e.g. myopotentials,
      electromechanical interference, etc., inadequate or incomplete physiological rate
      response to autonomic influences (devices have certain algorithms to address
      these issues) and most importantly the risk of infection. A biological pacemaker
      is therefore emerging as a promising technique to counter these challenges.

PMID- 30117444
TI  - Cisplatin-induced hearing loss in children with cancer.

PMID- 30117445
TI  - Insecticide-treated bednets for prevention of malaria.
AB  - Steinhardt LC, Jean YS, Impoinvil D, Mace KE, Wiegand R, Huber CS, Alexandre JSF,
      Frederick J, Nkurunziza E, Jean S, Wheeler B, Dotson E, Slutsker L, Kachur SP,
      Barnwell JW, Lemoine JF, Chang MA. (Division of Parasitic Diseases and Malaria,
      US Centers for Disease Control and Prevention, Atlanta, GA, USA; Programme
      National de la Controle de la Malaria, Ministere de la Sante Publique et de la
      Population, Port-au-Prince; Division of Global Health Protection, Centers for
      Disease Control and Prevention, Port-au-Prince; and Population Services
      International, Port-au-Prince, Haiti.) Effectiveness of insecticide-treated
      bednets in malaria prevention in Haiti: A case-control study. Lancet Glob Health
      2017;5:e96-e103.

PMID- 30117446
TI  - People with tuberculosis falling through the cracks.

PMID- 30117447
TI  - Identifying core competency areas to assess communication skills among interns at
      a tertiary teaching hospital in southern India.
AB  - Background.: We aimed to develop a teaching-learning and evaluation programme on
      communication skills for interns. Core competency areas for focused communication
      skills training and assessment were identified to achieve the obective. We then
      assessed the identified competencies among interns using objective structured
      clinical examination (OSCE), before the start of internship. Methods.: Five core
      areas for focused training and evaluation were identified on the basis of
      responses of practising physicians in local settings. OSCE stations were
      developed for evaluation based on the identified competency areas. A pre-test
      OSCE was administered to 30 interns. Results.: Five core areas selected for
      training and evaluation were: (i) communicating with a parent resistant to
      immunization; (ii) interacting with a patient who has psychosomatic complaints;
      (iii) explaining risks and procedures; (iv) breaking bad news; and (v)
      communicating with patients and bystanders in a casualty setting. Thirty of 160
      interns were selected to participate in the OSCE before the training (pre-test).
      The lowest score was for breaking bad news. Scores indicated that explaining
      risks and procedures, communicating in a busy casualty setting and dealing with
      psychosomatic complaints were areas that required extensive training and
      practice. Conclusions.: We were able to identify core competency areas for
      focused training and evaluation of communication skills suited to the local
      context and used OSCE to evaluate the skills before the start of internship.

PMID- 30117448
TI  - Effect of vestibular stimulation on spatial and verbal memory in college
      students.
AB  - Background.: Excessive stress may have an adverse effect on learning and memory
      of students. It was reported that stimulation of the vestibular system enhances
      memory through its connections with the hippocampus, limbic system and neo
      cortex. This study aims to assess the effectiveness of vestibular stimulation in
      the modulation of memory in healthy human subjects. Methods.: For this
      longitudinal follow-up study, we assessed spatial and verbal memory of
      participants followed by vestibular stimulation. A total of 240 healthy college
      students of 18-24 years, of either sex were selected after obtaining written
      consent from them. Participants were randomly assigned into four groups-control
      male and female group and vestibular male and female groups. Vestibular
      stimulation was administered by making the participants swing on a swing,
      according to their comfort (back to front direction) as standardized by previous
      methods. Spatial and verbal memory tests were used to assess memory. Data were
      analysed using two-way ANOVA followed by the Bonferroni post-hoc tests to compare
      differences between groups. Results.: Baseline values of spatial and verbal
      memory scores were not significantly different between the control and
      intervention groups. Significant enhancement was observed in spatial memory
      following vestibular stimulation in males but not female subjects. Contrary to
      this, significant decrease in spatial memory was observed in both males and
      females due to pre-examination stress who did not receive any vestibular
      stimulation. Significant enhancement was observed in verbal memory scores in both
      males and females who received vestibular stimulation, whereas verbal memory was
      significantly decreased in males and females in the control groups during the pre
      examination period. Conclusion.: Our study provides evidence to support
      vestibular stimulation as an efficient method to enhance memory and to prevent
      pre-examination associated stress-induced changes on memory. We recommend
      vestibular stimulation as a simple approach to improve verbal memory among
      students to cope with their pre-examination stress.

PMID- 30117449
TI  - Clinical research training and capacity building for prevention and control of
      non-communicable diseases: A programme in India.
AB  - Background.: Non-communicable diseases (NCDs)-a term which includes diabetes,
      cardiovascular disease, cancers, chronic respiratory diseases, and mental illness
      are now the major cause of death in India and pose healthcare and economic
      challenges. There is an urgent need for enhanced clinical research training and
      capacity building for NCD prevention and control in India. Methods.: We describe
      a multi-pronged approach funded in part by the US National Institutes of Health
      Fogarty International Center, which was initiated in 2001, to train Indian
      present and future scientists/doctors in NCD prevention and control. The
      approaches used were annual national seminars, intensive training courses, in
      house workshops, short-term training sessions in the USA and monthly video
      conferences. Results.: During 2001-2016, a total of 3650 undergraduate,
      postgraduate and faculty from medical colleges and institutes from almost all
      states in India and several neighbouring countries participated in seminars and
      other capacity-building workshops held at the Madras Diabetes Research
      Foundation, Chennai and at six other medical colleges; 883 delegates participated
      in the in-house workshops, 463 in the intensive interactive sessions; 244 in
      workshops on advanced techniques in genomics; and 37 in short-term training
      sessions held in the USA. Conclusion.: Through this unique capacity-building
      programme, more than 5000 individuals representing faculty and students from
      various medical colleges and research institutes across, and beyond, India,
      underwent training in the prevention and control of NCDs.

PMID- 30117450
TI  - Intraocular use of bevacizumab in India: An issue resolved?
AB  - Bevacizumab is a monoclonal antibody against vascular endothelial growth factor
      (VEGF), which has been approved for intravenous use in certain cancers. There is
      evidence of its efficacy and safety as an intravitreal drug compared with
      ranibizumab and aflibercept. We have, in our practice, found it to be a cost
      effective treatment option for ocular diseases, which could save a large amount
      of public money used in various national health insurance systems. An alert
      issued by the Drug Controller General of India led to a virtual ban on its
      intraocular use in India. However, pro-active advocacy and leadership by national
      ophthalmological societies helped to resolve the issue quickly.

PMID- 30117451
TI  - Errors of inclusion and exclusion in income-based provisioning of public
      healthcare: Problems associated with below poverty line cards.
AB  - This study examined the effect of out-of-pocket expenditure of patients on their
      illness and other household changes impacting on their well-being, and assessed
      the socioeconomic status and below poverty line (BPL) card status among patients
      at the All India Institute of Medical Sciences, New Delhi. We did a hospital
      based cross-sectional study of 374 inpatients and outpatients. Among the 374
      study subjects, more than 69% of poor did not possess a BPL card. On the other
      hand, 5.5% of the above poverty line patients among the respondents possessed a
      BPL card. Of those having BPL cards, 84.4% belonged either to the lower middle,
      upper lower and lower socioeconomic status categories. Our data suggest that the
      inaccuracies in providing BPL cards limit access of the genuine poor to
      healthcare. In the light of national-level surveys on accessing healthcare and
      out-of-pocket expenditure by patients there is a case against 'targeting' in the
      delivery of public health services and user charges have an adverse impact on
      access to healthcare by the poor.

PMID- 30117452
TI  - Letter from Chennai.

PMID- 30117453
TI  - Letter from Glasgow.

PMID- 30117454
TI  - Letter from Bristol.

PMID- 30117455
TI  - Obituaries.

PMID- 30117456
TI  - Mediastinal haematoma: A rare complication of central venous catheter insertion.

PMID- 30117457
TI  - Students' perceptions of gaps in teaching communication skills and behavioural
      sciences in undergraduate dental education.

PMID- 30117459
TI  - Chemical leukoderma due to hydroquinone: An unusual phenomenon.

PMID- 30117460
TI  - Entomodermoscopy: A tool for hunting bed bug.

PMID- 30117461
TI  - Dermoscopy: An easy way to solve the diagnostic puzzle in pityriasis versicolor.

PMID- 30117462
TI  - Bilateral agminated skin-colored papules and nodules on the dorsum of the hands.

PMID- 30117463
TI  - Authors' reply.

PMID- 30117464
TI  - IJDVL and impact factor.

PMID- 30117466
TI  - Attitudes toward mental illness among Caribbean medical students.
AB  - Background: There are limited empirical data on all matters pertaining to mental
      illness in the Caribbean but what little there is suggests significant levels of
      stigmatization exist. In this context, health professionals reveal at least equal
      to or only slightly improved attitudes to mental illness as compared to the
      general population. In addition, while there is evidence of improved attitudes
      among the population at large over the past decade this trend has not been
      observed among health professionals. This study, therefore, sought to assess
      medical students' knowledge about and attitudes toward mental illness as they
      traversed medical school. Methods: Preclinical medical students were surveyed and
      then retested in their final year of training. Students completed a knowledge
      scale, and the medical conditions regard scale comparing attitudes to four mental
      illness and three physical illness. Results: Knowledge about and attitudes toward
      mental illness showed significant improvement over the 5-year period. However,
      both preclinical and clinical students revealed significant levels of
      stigmatization toward mental illness despite improvements in knowledge. Students
      recognized the need to prioritize treatment for persons with mental illness but
      did not want to be personally involved in the treatment process. Discussion:
      Results highlight that significant negative attitudes still exist among medical
      students toward mental illness and these persist up until graduation. There is a
      need for further research into innovations and interventions to address this
      matter.

PMID- 30117468
TI  - Assessing the hidden curriculum for the care of patients with limited english
      proficiency: An instrument development.
AB  - Background: Patients with limited English proficiency (LEP) are a growing
      population in the United States at risk for disparities in quality and safety of
      care. Medical student competency to care for patients with LEP is impacted by a
      hidden curriculum (HC) that undermines the learning experience; yet to date,
      there is no way to measure it. Thus, we designed an instrument to assess this HC.
      Methods: Based on findings from previous qualitative work and input from medical
      students and experts in LEP and psychometrics, we developed a 23-item survey with
      four domains. We e-mailed this to 3rd and 4th year students from two medical
      schools in the US. We conducted principal axis factoring to determine the
      instrument's construct validity. Only items with a factor loading >=0.50 were
      retained. Results: We obtained 111 complete responses. Twenty-two of the 23
      original items were retained. Four factors/components emerged, which did not
      support the original proposed domains. Three factors loaded on a mix of role
      modeling, and learning environment, structural, and organizational variables,
      while the fourth factor retained two role modeling items. Based on the factor
      extraction solution, we restructured the instrument into three domains: role
      modeling, demonstration of effective systems, and consequences of structural
      barriers for patients with LEP (Cronbach's alpha: 0.81-0.95, total variance
      accounted for 53.7%). Discussion: The results led us to reassess the domain
      structure to create an instrument representing students' perceptions and context.
      Our instrument, the LEP-HC, will allow medical educators to investigate a
      specific and important HC and improve teaching about care of patients with LEP.

PMID- 30117469
TI  - Pre-University education curriculum reform and the generic learning skills of
      medical school entrants: Lessons learned from South Africa.
AB  - Background: Pre-university education curriculum changes may increase the skills
      and knowledge gap between secondary (high school) and tertiary (university)
      education that have been identified as having a major impact on the success of
      students from underresourced educational backgrounds. This study investigated the
      impact of extensive pre-university curriculum revision on the generic learning
      skills of entrants to South African medical schools, which admit students
      directly from high school. Methods: In this prospective study, students entering
      four medical schools during 2008-2011 were surveyed to determine their practice
      of and confidence in information handling, managing own learning, technical and
      numeracy skills, and computer, organizational, and presentation skills in the 12
      month preceding entry. The 2008 entrants were the final cohort of the old
      secondary school curriculum. The mean levels of practice or confidence of
      entrants to the four medical schools, during 2008-2011, were compared using
      analysis of variance. The Bonferroni's test was used for further pair-wise
      comparison of cohorts of students either entering in different years or different
      institutions. Results: While entrants at the four medical schools did not
      demonstrate a consistent or sustained change in their practice of or confidence
      in each skill category over the period of study, there were some significant
      differences between entrants at the respective institutions. Furthermore,
      entrants to one medical school were consistently less confident of their skills,
      despite more practice. These findings are best accounted for by the long-standing
      history of inequitably resourced pre-university education in South Africa.
      Discussion: These findings highlight the need for close monitoring of the impact
      of pre-university education changes on the learning skill profiles of university
      entrants, in order to design effective university programs which enable students
      from diverse backgrounds to participate and adequately meet curricula demands.

PMID- 30117467
TI  - Simulated patient and role play methodologies for communication skills training
      in an undergraduate medical program: Randomized, crossover trial.
AB  - Background: Educators utilize real patients, simulated patients (SP), and student
      role play (RP) in communication skills training (CST) in medical curricula. The
      chosen modality may depend more on resource availability than educational stage
      and student needs. In this study, we set out to determine whether an inexpensive
      volunteer SP program offered an educational advantage compared to RP for CST in
      preclinical medical students. Methods: Students and volunteer SPs participated in
      interactions across two courses. Students allocated to SP interactions in one
      course participated in RP in the other course and vice versa. Audio recordings of
      interactions were made, and these were rated against criterion descriptors in a
      modified Calgary-Cambridge Referenced Observation Guide. Results: Independent t
      test scores comparing ratings of RP and SP groups revealed no significant
      differences between methodologies. Discussion: This study demonstrates that
      volunteer SPs are not superior to RP, when used in CST targeted at preclinical
      students. This finding is consistent with existing literature, yet we suggest
      that it is imperative to consider the broader purpose of CST and the needs of
      stakeholders. Consequently, it may be beneficial to use mixed methods of CST in
      medical programs.

PMID- 30117470
TI  - The relationship between nursing instructors' clinical teaching behaviors and
      nursing students' learning in Tabriz University of Medical Sciences in 2016.
AB  - Background: Clinical teaching is at the core of the nursing profession. However,
      clinical teaching may not empower students to gain clinical competency and
      skills. In this context, the performance of instructors is one of the main
      determinants of effective clinical teaching. Therefore, the present study aimed
      to determine the relationship between nursing instructors' clinical teaching
      behaviors and students' learning. Methods: This descriptive, correlational study
      was conducted with 267 nursing students selected through convenience sampling.
      The data were collected using the Nursing Clinical Teacher Effectiveness
      Inventory, developed by Knox and Morgan. The questionnaire included two parts:
      the extent to which nursing instructors used teaching behaviors and the
      effectiveness of these behaviors on students' learning. The data were entered
      into the SPSS statistical software, version 19, and were analyzed using
      descriptive and inferential statistics and the Pearson's correlation coefficient.
      Results: The results showed a significant positive relationship between the
      extent to which nursing instructors used teaching behaviors and the effectiveness
      of these behaviors on students' learning (P = 0.001). In terms of the utilization
      of teaching behaviors, the highest average rates were related to the dimensions
      of interpersonal relations and teaching abilities, while the lowest average rates
      were found for the evaluation dimension. With regard to the effectiveness of
      these teaching behaviors on learning, the dimensions of teaching ability and
      evaluation gained the highest and lowest average rates, respectively. Discussion:
      Instructors' capabilities have to be improved regarding the effective utilization
      of some behaviors related to evaluation, personal characteristics, and nursing
      competency. In this respect, the use of comprehensive teaching programs can be
      quite beneficial.

PMID- 30117471
TI  - A review of mastery learning: The roseman model as an illustrative case.
AB  - Background: An educational method gaining acceptance in health profession's
      training is mastery learning. Mastery learning requires learners to demonstrate
      essential knowledge and skills measured against rigorously set standards without
      regard to time. The key elements of mastery learning include focus on a single
      subject, short curricular blocks, setting specific objectives, using frequent
      feedback, deliberative practice, and demonstrating mastery before moving onto the
      next subject. Roseman University of the Health Sciences College of Pharmacy (COP)
      developed and delivered an accelerated mastery learning curriculum designed to
      develop knowledge and skills through active learning. Methods: The COP uses a
      mastery model for its PharmD program. The didactic curriculum is divided into 2
      week assessment blocks focusing on a single subject. Students must demonstrate
      mastery, defined as >=90% on an assessment, to pass a block. Students failing a
      block assessment receive feedback and a second opportunity to pass. Students
      failing their repeat assessment continue onto the next block, but require summer
      remediation before moving onto the next year. Results: National pass rates for
      the US pharmacy board examination ranged between 92.6% and 96.9% during the 2010
      2015 period, while the COP scores ranged from 93.0% to 99.0% and fell below
      national pass rates on only one occasion. The attrition rate was 6.5%, below the
      national rate of 10.8%. Students reported an overall satisfaction with their
      education of 3.82 (Likert scale 1-5) and 4.04 for the block system. Discussion:
      Overall, the Roseman University mastery model is successful. Students report high
      levels of satisfaction and outcomes on examinations and attrition compares
      favorably to national averages.

PMID- 30117474
TI  - Do perceptions about educational environment influence academic performance? A
      cross-sectional study of undergraduate medical students in Madurai, South India.

PMID- 30117473
TI  - Enhancing medical student diversity through a premedical program: A Caribbean
      school case study.
AB  - Background: Physicians with backgrounds underrepresented in medicine (URiM) are
      more likely to practice in underserved communities. Recruitment into and
      assistance during medical education has the potential to increase the number of
      URiM physicians. This study analyzes URiM students' academic performance at a
      well-established Caribbean school with and without prior successful completion of
      the Medical Education Readiness Program (MERP). Methods: A retrospective analysis
      of premedical school requirements and achievements in medical school were
      performed for URiM students enrolled in Ross University School of Medicine
      between 2006 and 2012, through either MERP or direct admission. For MERP and non
      MERP students, an independent sample two-tailed Student t-test was used to
      compare prerequisite Grade Point Average (p GPA), Medical College Admission Test
      (MCAT), and The United States Medical Licensing Examination (USMLE) Step 1
      scores. Chi-square analysis was performed to compare the attrition rates for MERP
      and non-MERP URiM students in the first years of medical schools well as USMLE
      Step 1 pass rates. Results: A total of 1299 students entering medical school
      directly (n = 981) or through MERP (n = 318) were evaluated. The mean MCAT (19.6
      for MERP vs. 21.6 for non-MERP, P < 0.001) and prerequisite GPA (2.8 for MERP vs.
      3.1 for non-MERP, P < 0.001) were significantly lower for the MERP students. A
      similar percentage of MERP and non-MERP students reached the 2nd year (83.0% and
      80.9% respectively, P = 0.407) and 3rd year (80.5% and 79.0% respectively, P =
      0.565) of medical school. USMLE Step 1 pass rates for MERP (90.6%) and non-MERP
      (92.3%) as well as USMLE Step 1 mean scores (208.9 and 210.0 for MERP and non
      MERP, respectively) were also comparable. Discussion: MERP-like programs can help
      URiM students with lower undergraduate scores succeed in medical school.

PMID- 30117472
TI  - Understanding the fundamental elements of global health: Using the sen capability
      approach as the theoretical framework for a health needs assessment in deprived
      communities.
AB  - Background: The health needs in poor communities are often dictated by data that
      is not relevant to the community. The capabilities approach (CA) offers a
      philosophical and practical way to frame and analyse data and apply it to a
      community using the World Health Organisation socioeconomic framework. This was
      part of the NHS Health Education England East Midlands Global Health Exchange
      Fellow Programme. Methods: A team of 2 Kenyan and 2 UK community clinicians
      worked together in deprived communities in Kenya and the UK using qualitative
      research methods to facilitate the communities to define and prioritise their
      health needs and to explore their potential resources and how they might achieve
      their needs sustainably. The CA was used in the data collection and data analysis
      phases. Results: The team of fellows gained personal understanding of the reality
      of the impact of social determinants on health experiences and outcomes. The CA
      offers the health systems and services a way to engage hard to reach communities
      with issues that they know to be important and are then able to prioritise.
      Clinicians who are taught in the evidence based style need to reframe their
      understanding of community needs if they are to be effective in their work.
      Working in this way can challenge their own values and beliefs. With planned
      support this can be a powerful developmental process and the CA is a set of
      principles that can be used to facilitate the empowerment of communities, the
      service planners and providers.

PMID- 30117475
TI  - What do medical students think about health-care policy education?

PMID- 30117477
TI  - Resident-to-resident handoff of primary care practice when transitioning to an
      inpatient rotation.

PMID- 30117476
TI  - Scientific misconduct in publication among medical students: Education and role
      model.

PMID- 30117478
TI  - SNAPPS facilitates clinical reasoning in outpatient settings.

PMID- 30117480
TI  - Recurrent takotsubo cardiomyopathy in a postmenopausal Indian lady: Is there a
      pattern?
AB  - Takotsubo cardiomyopathy (TTC) is a syndrome of acute left ventricular
      dysfunction with a clinical presentation often mimicking acute coronary syndrome.
      Without a high index of suspicion, this clinical entity often goes unrecognized.
      Although initially categorized as a benign completely reversible condition, it is
      no longer considered to be so. Recurrence of this condition, though rare, has
      been reported in a non-Indian population. We present a case of recurrent TTC in a
      postmenopausal Indian lady who had a similar clinical presentation both at the
      index event and at recurrence.

PMID- 30117481
TI  - Proptosis and hemiplegia as an initial manifestation of multiple myeloma.
AB  - Multiple myeloma (MM) is a monoclonal gammopathy, also known as the malignant
      proliferation of plasma cells, presenting with typical complications such as
      hypercalcemia, osteolytic bone lesions, anemia, renal insufficiency, and frequent
      infections. Central nervous system (CNS) involvement in MM in the form of
      parenchymal involvement is very uncommon and has been reported only in 1% of
      patients. CNS involvement as an initial presentation is very rare and has poor
      prognosis. Also specific treatment guidelines do not exist for the treatment of
      such patients. We present here a case of a 40-year-old female patient, with
      complaints of headache and left eye proptosis followed by left-sided hemiparesis,
      who after complete workup was diagnosed as a de novo case of stage III
      extramedullary MM with CNS involvement. Patient was treated with whole brain
      radiation followed by BCD regimen (injection of bortezomib, injection of
      cyclophosphamide, and tablet dexamethasone). After three cycles of chemotherapy,
      patient succumbed in view of consolidation and renal failure.

PMID- 30117482
TI  - Endo-hepatology: A new paradigm.

PMID- 30117483
TI  - EUS-guided paracentesis and ascitic fluid analysis.

PMID- 30117485
TI  - Role of EUS-guided liver biopsy in benign parenchymal disease (with video).

PMID- 30117484
TI  - EUS-guided vascular interventions.

PMID- 30117486
TI  - EUS-guided portal vein sampling.
AB  - EUS provides real-time images of the intramural gastrointestinal tract and
      adjacent structures that otherwise would not be visible. Given the anatomic
      proximity to the bowel, accurate identification of the major abdominal
      vasculature, such as the portal vein, serves as a useful landmark tool for
      identifying anatomy and staging of malignancies. Recently, increased reports have
      centered on the utility of EUS-guided vascular access of the portal vein for
      diagnostic and therapeutic interventions. Pilot and feasibility studies in human
      patients utilizing EUS-guided portal vein access for circulating tumor cell
      enumeration and portal pressure gradient monitoring suggest that sampling the
      portal vein under EUS guidance is safe and effective. This review discusses the
      rationale and technical aspects of EUS-guided portal vein sampling for diagnostic
      purposes in gastrointestinal cancer. Understanding the technical aspects of EUS
      guided portal vein sampling will be critical to standardizing the procedure,
      developing new vascular access technologies, and increasing the safety profile.

PMID- 30117487
TI  - EUS anatomy of the liver segments.
AB  - Clinical applications of EUS for the liver have been recently increasing. They
      include the screening and diagnosis of liver parenchymal disease and malignant
      tumors as well as EUS-guided interventions such as hepaticogastrostomy, tumor
      ablation therapy, and portal pressure gradient measurement. Although the
      segmental localization of the targeted tumor, bile duct, and vessel in the liver
      is important to complete these procedures, little information is available
      regarding hepatic segmental anatomy on EUS. The liver can be visualized with EUS
      by transgastric and transduodenal scanning, and the EUS determination of
      segmental location can be achieved using various anatomical landmarks.
      Identification of the right posterior segments is, however, technically difficult
      because they are located far from the stomach and duodenum. In the present
      review, we describe the normal anatomy of liver segments using linear EUS.

PMID- 30117488
TI  - EUS liver assessment using contrast agents and elastography.
AB  - Transabdominal-US is the first-line imaging modality used to assess the whole
      liver parenchyma and vascularization; EUS assessment of the liver is incomplete
      and is not sufficient to rule out the presence of focal liver lesions. On the
      other hand, due the high diagnostic yield in detecting very small (< 1 cm)
      lesions, EUS is considered complementary to radiological imaging techniques for
      the investigation of liver parenchyma. Scarce data are available regarding the
      investigation of liver parenchyma using both EUS-elastography (EUS-E) and CH-EUS.
      The aim of this review is to evaluate the clinical role of image enhancement
      techniques, namely EUS-E and contrast harmonic-EUS (CH-EUS), for the evaluation
      liver diseases. Despite a potential interest for the application of EUS-E in the
      assessment of liver diseases, available evidence relegates this technique only to
      research areas, such as the differential diagnosis between benign and malignant
      focal liver lesions and the quantification of liver fibrosis in diffuse
      parenchymal diseases. With the future introduction of EUS shear-wave
      elastography, interesting data can be obtained for the assessment of liver
      fibrosis during real-time EUS evaluation. The usefulness of CH-EUS for the
      evaluation of liver disease is limited by the intrinsic EUS ability to explore
      only the left lobe and a small part of the right lobe. CH-EUS could be used to
      increase the diagnostic ability of EUS for the detection and characterization of
      small lesions and for guiding tissue sampling. Targeting EUS-guided treatments
      with either EUS-E or CH-EUS might represent potential future applications.

PMID- 30117489
TI  - EUS-guided portal pressure measurement (with videos).
AB  - A growing number of studies have explored EUS-guided vascular catheterization due
      to the relative proximity of the gastrointestinal tract to the major blood
      vessels of the mediastinum and abdomen. In particular, EUS-guided access of the
      portal vein (PV) may be favorable given the relative difficulty of PV access
      through standard percutaneous routes. Two major diagnostic applications of EUS
      guided vascular access include angiography and assessment of intravascular
      pressure. This review will outline the different devices and techniques employed
      to obtain angiographic visualization and/or direct pressure measurements of the
      portal circulation. Ease of access, safety, and important lessons learned from
      each approach will be highlighted.

PMID- 30117490
TI  - Treatment efficacy of ledipasvir/sofosbuvir for 8 weeks in non-cirrhotic chronic
      hepatitis C genotype 4 patients.
AB  - Background/Aims: Ledipasvir/sofosbuvir (LDV/SOF) combination is administered for
      12 to 24 weeks to treat hepatitis C virus (HCV); guidelines recommend 8 weeks
      treatment duration for HCV genotype (GT) 1 infection based on the patient's
      baseline characteristics. Data on treating HCV GT4 with LDV/SOF are limited. In
      this prospective cohort study, the efficacy and safety of 8 weeks treatment
      duration with LDV/SOF was evaluated in HCV GT4 patients in Saudi Arabia. Patients
      and Methods: Treatment-naive, non-cirrhotic HCV GT4 patients received LDV/SOF for
      8 weeks. HCV RNA levels and laboratory evaluations were recorded at baseline and
      at Weeks 4, 8, and 20. The primary endpoint was sustained virologic response 12
      weeks after the end of the treatment (SVR12). Safety data were also recorded.
      Results: Forty-five patients with a mean age of 43.9 +/- 17.2 years participated,
      of whom 57.8% were male. Mean log10HCV RNA was 6.26 +/- 6.32 IU/mL and most
      (91.1%) had baseline HCV RNA levels <6 million IU/mL. The most frequent
      comorbidities were hypertension and diabetes mellitus (20.0% each). Concomitant
      medication was taken by 18 patients (40.0%), of whom two took proton pump
      inhibitors. Overall, SVR12 was 97.8% (95% confidence interval [CI]: 88.2%-99.9%);
      one patient (2.2%) relapsed post treatment. No serious adverse events or
      discontinuations were reported. Eighteen patients (44.4%) had 38 adverse events
      related to LDV/SOF; the most frequent was headache. Conclusions: An 8-week
      regimen of LDV/SOF was well tolerated and efficacious in this treatment-naive,
      non-cirrhotic HCV GT4-infected population. This study provides valuable
      information on a short treatment regimen for HCV GT4 infection in a real-world
      setting.

PMID- 30117491
TI  - In-hospital post-transplant acute hepatitis A viral (HAV) infection in a liver
      transplant recipient who was HAV seropositive pre-transplant.
AB  - Acute hepatitis A viral (HAV) infection is rare in the liver transplant
      population due to recommended pre-transplant vaccinations. We report a case of
      acute hepatitis A infection in a liver transplant recipient. This individual had
      immunity to hepatitis A with protective IgG antibodies and presented with
      abnormal liver biochemistry in the post-transplant in-patient setting. Hepatitis
      A infection was confirmed by positive HAV IgM whereas other etiologies, including
      acute cellular rejection, were ruled out by laboratory tests and liver biopsies.
      He was treated conservatively with supportive care and liver enzymes recovered to
      normal baseline. Despite adequate pre-transplant immunity, in the post-transplant
      setting there may be loss of protective immunity due to profound
      immunosuppression and hence hepatitis A should remain an important differential
      diagnosis in the setting of acute hepatitis.

PMID- 30117492
TI  - Radiofrequency ablation versus surgical resection in elderly patients with early
      stage hepatocellular carcinoma in the era of organ shortage.
AB  - Background/Aims: To compare the survival benefits of surgical resection (SR) with
      those of radiofrequency ablation (RFA) in elderly patients (>=65 years) with
      single hepatocellular carcinoma (HCC) <=5 cm. Patients and Methods: Using the
      Surveillance, Epidemiology, and End Results database, a total of 461 patients who
      underwent SR and 575 patients who underwent RFA were enrolled from 2004 to 2012.
      Overall survival (OS) and liver-cancer-specific survival (LCSS) comparisons were
      conducted between the two groups before and after propensity score matching
      (PSM). Results: Elderly patients with early-stage HCC had a lower rate of
      utilization of liver transplantation, and they were more likely to receive SR or
      RFA as their first-line treatment compared with younger patients (P < 0.05). In
      the whole cohort, the SR group had significantly better OS [RFA, hazard ratio
      (HR) = 1.680 (1.390, 2.031), P < 0.001] and LCSS (RFA, HR = 1.658 (1.327, 2.070),
      P < 0.001) than the RFA group. After PSM, the improved survival in the SR group
      was further confirmed (all P < 0.001). In the subgroup analyses, according to
      patients' age (65-75, >75 years) and tumor size (<=3.0, 3.1-5.0 cm), the SR group
      still presented better OS and LCSS than the RFA group (all P < 0.05), except for
      those older than 75 years with tumors <=3.0 cm (all P > 0.05), both before and
      after PSM. Conclusion: Treatment strategies for elderly patients (>=65 years)
      with single HCC <=5 cm should emphasize SR as the primary therapy, while RFA can
      be an alternative to SR for those> 75 years with single HCC <=3 cm.

PMID- 30117493
TI  - Extraintestinal manifestations of pediatric inflammatory bowel disease in Saudi
      Arabia.

PMID- 30117494
TI  - Increased Expression of CD81 in Breast Cancer Tissue is Associated with Reduced
      Patient Prognosis and Increased Cell Migration and Proliferation in MDA-MB-231
      and MDA-MB-435S Human Breast Cancer Cell Lines In Vitro.
AB  - BACKGROUND CD81, a member of the tetraspanin family, is overexpressed in several
      tumor types, but its role in breast cancer remains unknown. The present study
      aimed to investigate the effects of increased CD81 expression on cell migration
      and proliferation in breast cancer cell lines, MDA-MB-231 and MDA-MB-435S in
      vitro, and the effects of increased CD81 expression in breast cancer tissue
      microarrays on patient prognosis. MATERIAL AND METHODS The expression of CD81 was
      evaluated using immunohistochemistry in a human breast cancer tissue microarray
      containing 140 tumor tissues and a microarray containing 77 normal breast
      tissues. The effects of increased CD81 expression on cell proliferation and
      migration in breast cancer cell lines, MDA-MB-231 and MDA-MB-435S, were evaluated
      by proliferation, transwell migration, and cell counting kit-8 (CCK-8) assays.
      CD81-expressing plasmid transfection upregulated CD81 expression, and short
      hairpin RNA (shRNA) lentivirus silenced CD81 expression in vitro. RESULTS CD81
      expression was significantly increased in breast cancer tissues compared with
      normal breast tissues (P<0.05). Increased expression of CD81 was significantly
      associated with lymph node metastasis (P<0.05), clinical stage (P<0.05) and with
      reduced overall survival (OS) in patients with breast cancer (P<0.05). Increased
      CD81 expression in MDA-MB-231 and MDA-MB-435S cells promoted cell proliferation
      and migration, which were inhibited by CD81 silencing. CONCLUSIONS The findings
      of the study showed that CD81 might be a potential prognostic biomarker
      associated with poor patient prognosis in breast cancer. These findings should be
      investigated further with large-scale controlled prospective studies in patients
      with breast cancer.

PMID- 30117495
TI  - The Fifth Asian Indoor and Martial Arts Games in Turkmenistan - A dentist's
      perspective.
AB  - This article is a personal view of two dentists who were invited to attend the
      recent Fifth Asian World Indoor and Martial Arts Championships in Ashgabat,
      Turkmenistan. We relate the issues of getting to the venue, challenges during our
      stay and the role of the dentist in the sporting arena.

PMID- 30117496
TI  - Social dentistry: an old heritage for a new professional approach.
AB  - If dental professionals want to improve the oral health of their patients, they
      need to address what makes them sick: the social determinants of health. In this
      article, we propose a model of 'social dentistry' that shows how dentists could
      tackle these fundamental causes of oral disease. Socially engaged dentists
      conduct actions at three levels. At the individual level, they provide patient
      centred care and, when necessary, liaise with local resources to better address
      what makes their patients sick. At the community level, they adapt their practice
      to the needs of the most vulnerable groups and advocate for healthier local
      policies. At the societal level, they are engaged in upstream actions addressing
      the social determinants of health.

PMID- 30117497
TI  - The history of dental bodies corporate and the role of the BDA in their
      development.
AB  - Dental bodies corporate are not a new phenomenon with companies having practised
      dentistry in the UK for over a hundred years. At the turn of the twentieth
      century, unregistered practice was common with dental companies resulting in
      extensive malpractice. Corporate dentistry introduced commercial interests into
      the profession and brought further dangers such as treatment not being patient
      centred. The British Dental Association (BDA) was among those who continuously
      worked to mitigate these effects. Increasingly strict measures were introduced by
      governments to protect the public from harm from corporate practice with the
      government eventually remedying concerns, in the 1950s, by restricting corporate
      practice. In 2006 this restriction was lifted, with the support of the BDA, in an
      effort to increase competition and choice and open up the market to new
      providers. While the profession continues to develop, concerns remain. Some are
      long held with others, such as a negative effect on working conditions and UDA
      values, being relatively recent developments.

PMID- 30117498
TI  - In their own words: investigating the preparedness of final year dental students
      in the UK for independent general dental practice.

PMID- 30117499
TI  - Should wrong extraction site be classed as a never event?
AB  - NHS England has set out plans for combatting the rise in never events in the
      realm of dentistry. This Opinion article investigates the root cause of never
      events, whether a wrong site surgery should be deemed a never event, and whether
      the approaches adopted to reduce risk exposure, such as local safety standards
      for invasive procedures (LocSSIPS), are helping or hindering safe medical care.

PMID- 30117500
TI  - Mobile genetic elements and genome evolution 2014.
AB  - The Mobile Genetic Elements and Genome Evolution conference was hosted by
      Keystone Symposia in Santa Fe, NM USA, 9 March through 14 March 2014. The goal of
      this conference was to bring together scientists from around the world who study
      transposable elements in diverse organisms and researchers who study the impact
      these elements have on genome evolution. The meeting included over 200 scientists
      who participated through poster presentations, short talks selected from
      abstracts, and invited speakers. The talks were organized into eight sessions and
      two workshops. The topics varied from diverse mechanisms of mobilization to the
      evolution of genomes and their defense strategies against transposable elements.

PMID- 30117502
TI  - Correction: Dysregulation of miRNAs expression levels and disease activity in SLE
      patients.
AB  - [This corrects the article DOI: 10.1136/lupus-2017-000215.317.][This corrects the
      article DOI: 10.1136/lupus-2017-000215.317.].

PMID- 30117501
TI  - Correction to: Meeting report from the fourth meeting of the Computational
      Modeling in Biology Network (COMBINE).
AB  - [This corrects the article DOI: 10.4056/sigs.5279417.].

PMID- 30117503
TI  - Design, synthesis, and biological evaluation of C7-functionalized DMXAA
      derivatives as potential human-STING agonists.
AB  - STING, a central protein in the innate immune response to cytosolic DNA, has
      emerged as a hot target for the development of vaccine-adjuvants and anticancer
      drugs. The discovery of potent human-STING (hSTING) agonist is expected to
      revolutionize the current cancer immunotherapy. Inspired by the X-ray crystal
      structure of DMXAA (5,6-dimethylxanthenone-4-acetic acid) and hSTINGG230I
      complex, we designed various DMXAA derivatives that contain a hydrogen bonding
      donor/acceptor or a halide at the C7 position. While 7-bromo- and 7-hydroxyl
      DMXAA showed notable binding to mouse-STING (mSTING), our newly synthesized C7
      functionalized DMXAA derivatives did not bind to hSTING. Nevertheless, our newly
      developed synthetic protocol for the C7-functionalization of DMXAA would be
      applicable to access other C7-substituted DMXAA analogues as potential hSTING
      agonists.

PMID- 30117504
TI  - Tracking mitochondrial dynamics during apoptosis with phosphorescent fluorinated
      iridium(iii) complexes.
AB  - Mitochondria are the control centers of apoptosis. To study mitochondrial
      dynamics during apoptosis, four phosphorescent fluorinated iridium(iii) complexes
      (Ir1-Ir4) were designed and synthesized. The complexes' emission maxima,
      phosphorescent quantum yields, and phosphorescent lifetimes are tuned by the
      degree of fluorination of the ligand. The complexes exhibit excellent
      photostability and low (photo)cytotoxicity in HeLa cells. As the complexes are
      cationic and lipophilic, they localize in mitochondria and enter cells through an
      energy-independent pathway. In comparison with commercially available
      mitochondrial trackers (e.g., MTR), Ir1-Ir4 exhibit high specificity to
      mitochondria even in fixed cells. Due to these outstanding properties, the
      complexes were successfully used to track mitochondrial dynamics during
      apoptosis.

PMID- 30117505
TI  - Elemental doping for optimizing photocatalysis in semiconductors.
AB  - The exploration of advanced photocatalysts has been attracting wide attention,
      especially in facing the recent growing challenges of energy and environment.
      Among the various strategies for achieving high solar energy utilization,
      elemental doping has been extensively explored owing to its advantages in tuning
      the electronic structures of semiconductor-based catalysts, where the key factors
      in photocatalysis can be generally optimized. This frontier article will focus on
      the impacts of elemental doping on light absorption, band positions and charge
      carrier processes of semiconductors.

PMID- 30117506
TI  - Stokes and anti-Stokes Raman scattering in mono- and bilayer graphene.
AB  - Stokes and anti-Stokes Raman spectroscopy associated with the intervalley double
      resonance process in carbon materials is a unique technique to reveal the
      relationship between their characteristic electronic band structures and phonon
      dispersion. In graphene, the dominant resonant behavior for its 2D mode is an
      intervalley triple resonance Raman process. In this paper, we report the Stokes
      and anti-Stokes Raman scattering of the 2D mode in pristine graphene. The
      excitation energy (Eex)-dependent frequency discrepancy between anti-Stokes and
      Stokes components of the 2D mode (Deltaomega(2D)) is observed, which is in good
      agreement with the theoretical results. This is attributed to the nonlinear
      dispersion of the in-plane transverse optical (iTO) phonon branch near the K
      point, confirmed by the nonlinear Eex-dependent frequency of the 2D mode
      (omega(2D)) in the range of 1.58-3.81 eV. The wavevector-dependent phonon group
      velocity of the iTO phonon branch is directly derived from Deltaomega(2D). The
      Stokes and anti-Stokes Raman scattering of the D mode in defected graphene and
      the 2D mode in bilayer graphene associated with intervalley double resonance
      Raman processes is also reported.

PMID- 30117507
TI  - Quinoline-galactose hybrids bind selectively with high affinity to a galectin-8 N
      terminal domain.
AB  - Quinolines, indolizines, and coumarins are well known structural elements in many
      biologically active molecules. In this report, we have developed straightforward
      methods to incorporate quinoline, indolizine, and coumarin structures into
      galactoside derivatives under robust reaction conditions for the discovery of
      glycomimetic inhibitors of the galectin family of proteins that are involved in
      immunological and tumor-promoting biological processes. Evaluation of the
      quinoline, indolizine and coumarin-derivatised galactosides as inhibitors of the
      human galectin-1, 2, 3, 4N (N-terminal domain), 4C (C-terminal domain), 7, 8N,
      8C, 9N, and 9C revealed quinoline derivatives that selectively bound galectin-8N,
      a galectin with key roles in lymphangiogenesis, tumor progression, and autophagy,
      with up to nearly 60-fold affinity improvements relative to methyl beta-d
      galactopyranoside. Molecular dynamics simulations proposed an interaction mode in
      which Arg59 had moved 2.5 A and in which an inhibitor carboxylate and quinoline
      nitrogen formed structure-stabilizing water-mediated hydrogen bonds. The
      compounds were demonstrated to be non-toxic in an MTT assay with several breast
      cancer cell lines and one normal cell line. The improved affinity, selectivity,
      and low cytotoxicity suggest that the quinoline-galactoside derivatives provide
      an attractive starting point for the development of galectin-8N inhibitors
      potentially interfering with pathological lymphangiogenesis, autophagy, and tumor
      progression.

PMID- 30117508
TI  - Structure and behaviour of vesicles in the presence of colloidal particles.
AB  - This review highlights recent studies that investigate the structural changes and
      behaviour of synthetic vesicles when they are exposed to colloidal particles. We
      will show examples to demonstrate the power of combining particles and vesicles
      in generating exciting supracolloidal structures. These suprastructures have a
      wide range of often responsive behaviours that take advantage of both the
      mechanical and morphological support provided by the vesicles and the associated
      particles with preset functionality. This review includes applications spanning a
      variety of disciplines, including chemistry, biology, physics and medicine.

PMID- 30117509
TI  - Effect of sulfur doping on structural reversibility and cycling stability of a
      Li2MnSiO4 cathode material.
AB  - Based on the existing calculation reports, sulfur doping is an effective approach
      to alleviate the structure collapse of Li2MnSiO4 during cycling. Herein, we
      investigate the feasibility and limitations of S doping in Li2MnSiO4 by
      experiment. In our work, the solid solubility of S is confirmed and exceeding the
      threshold results in MnS impurity. The existence state and site of the S element
      in a Li2MnSiO4 crystal structure is also confirmed. It is found that S doping
      significantly improves the structural reversibility and cycling stability.
      Compared with a pristine sample, a 1mol% S doped sample exhibits a much higher
      initial coulombic efficiency (88.3%), excellent capacity retention (98% at 10th
      cycles for instance) and enhanced rate performance. Moreover, the 1mol% S doped
      sample can retain a discharge capacity of 137 mA h g-1 after 30 cycles while the
      pristine sample only has 61.6 mA h g-1. This study confirms the effectivity of S
      doping in suppressing the structural distortion in Li2MnSiO4.

PMID- 30117510
TI  - Efficient loading of ophthalmic drugs with poor loadability into contact lenses
      using functional comonomers.
AB  - Ophthalmic formulations have classically been administered to eyes through eye
      drops, which have poor delivery efficiency and require frequent instillation. As
      a means of overcoming these drawbacks, ocular-drug delivery via therapeutic
      contact lenses has caused great interest. A simple way to prepare therapeutic
      contact lenses is to immerse lenses in concentrated drug solution. However, not
      all ocular drugs can be efficiently loaded into contact lenses by a simple
      soaking. In particular, our previous study showed that two antibacterial ocular
      drugs, ofloxacin (OFX) and neomycin (NEO), were poorly loaded to poly(2
      hydroxyethyl methacrylate) (pHEMA)-based contact lenses. Herein, we investigated
      whether alteration of lens composition using several negatively charged
      comonomers can enhance loading of ocular drugs with poor loadability (OFX and
      NEO). As comonomers, methacrylic acid (MAA), acrylic acid (AA), and 4-methyl-4
      pentenoic acid (MPA) were used, generating p(HEMA-co-MAA), p(HEMA-co-AA), and
      p(HEMA-co-MPA) hydrogel-based contact lenses, respectively. Contact lenses
      containing comonomers exhibited an increase in loading of OFX and NEO. In
      particular, compared with pHEMA contact lenses, contact lenses containing 2.5
      mol% AA exhibited enhanced loading of OFX and NEO, 18 and 53 times, respectively.
      Charge interactions between comonomers and the drug were considered primary
      factors in the substantial increase in drug loading.

PMID- 30117511
TI  - Native chemical ligation at methionine bioisostere norleucine allows for N
      terminal chemical protein ligation.
AB  - The development of gamma-thionorleucine (ThioNle) as a handle for native chemical
      ligation-desulfurization is reported here. ThioNle is a new addition to the
      expanding thiolated amino acid toolbox and serves as a methionine substitute in
      NCL with the advantage that it lacks the undesirable oxidation-prone thioether
      moiety. Its usefulness for N-terminal ubiquitination is demonstrated by efficient
      preparation of fully synthetic linear diubiquitin with preserved protein folding
      compared to the expressed material. Interestingly, gel-based deubiquitinating
      assays revealed that the methionine to norleucine substitution did affect
      diubiquitin cleavage, which may indicate a more profound role for methionine in
      the interaction between ubiquitin and the deubiquitinating enzymes than has been
      known so far.

PMID- 30117512
TI  - 1,2,4-Triazolium ions as flexible scaffolds for the construction of polyphilic
      ionic liquid crystals.
AB  - A novel scaffold for the construction of self-organised ionic liquids and ionic
      liquid crystals bearing both perfluorocarbon and hydrocarbon moieties has been
      developed. The phase behaviour and physical properties of these materials can be
      tuned as a function of chain length and fluorine content and significant
      structural elaboration is possible, giving a highly flexible system.

PMID- 30117513
TI  - Ferrocene-based anilides: synthesis, structural characterization and inhibition
      of butyrylcholinesterase.
AB  - Twenty-three compounds in two series of ferrocene-based anilides, with the
      general formula C5H5-Fe-C5H4-C6H4-NH-CO-C6H4-R (where R = H, F, Cl, CH3 and
      OCH3), have been successfully synthesized. The compounds were characterized by
      elemental analysis and FTIR, 1H NMR and 13C NMR spectroscopy. Two compounds (M07
      and P09) were characterized by X-ray crystallography. Solid state studies
      indicate that ferrocene derivatives with the conformation of meta amide
      substituents engage in intermolecular H-bonding, which stabilizes the meta
      derivatives over their para analogues. The H-bonding takes place when the
      conformation of the ferrocene changes by rotation around the C-N bond, favoring
      interactions between two molecules in adjacent layers in the solid state. The
      potential importance of this H-bonding to the biological effects of these
      molecules was investigated using both experimental and computational studies. All
      the compounds were found to inhibit butyrylcholinesterase. The most active
      compound shows 50% inhibition at a concentration of 9 +/- 0.2 MUM, similar to the
      known drug galantamine (with an IC50 of 8 MUM). Compounds with the ferrocene
      moiety meta to the amide linkage were consistently found to be slightly more
      active than the other structural isomers, suggesting that the H-bonding may only
      slightly increase the overall affinity for the protein. Computational studies
      confirmed the limited effects of the H-bonding in the presence and absence of
      water in the active site of butyrylcholinesterase, supporting the importance of
      hydrophobicity for inhibitors of this enzyme.

PMID- 30117514
TI  - A 96-well microplate bioreactor platform supporting individual dual perfusion and
      high-throughput assessment of simple or biofabricated 3D tissue models.
AB  - Traditional 2D monolayer cell cultures and submillimeter 3D tissue construct
      cultures used widely in tissue engineering are limited in their ability to
      extrapolate experimental data to predict in vivo responses due to their
      simplistic organization and lack of stimuli. The rise of biofabrication and
      bioreactor technologies has sought to address this through the development of
      techniques to spatially organize components of a tissue construct, and devices to
      supply these tissue constructs with an increasingly in vivo-like environment.
      Current bioreactors supporting both parenchymal and barrier tissue constructs in
      interconnected systems for body-on-a-chip platforms have chosen to emphasize
      study throughput or system/tissue complexity. Here, we report a platform to
      address this disparity in throughput and both system complexity (by supporting
      multiple in situ assessment methods) and tissue complexity (by adopting a
      construct-agnostic format). We introduce an ANSI/SLAS-compliant microplate and
      docking station fabricated via stereolithography (SLA), or precision machining,
      to provide up to 96 samples (O6 * 10 mm) with two individually-addressable fluid
      circuits (192 total), loading access, and inspection window for imaging during
      perfusion. Biofabricated ovarian cancer models were developed to demonstrate the
      in situ assessment capabilities via microscopy and a perfused resazurin-based
      metabolic activity assay. In situ microscopy highlighted flexibility of the
      sample housing to accommodate a range of sample geometries. Utility for drug
      screening was demonstrated by exposing the ovarian cancer models to an anticancer
      drug (doxorubicin) and generating the dose-response curve in situ, while
      achieving an assay quality similar to static wellplate culture. The potential for
      quantitative analysis of temporal tissue development and screening studies was
      confirmed by imaging soft- (gelatin) and hard-tissue (calcium chloride) analogs
      inside the bioreactor via spectral computed tomography (CT) scanning. As a proof
      of-concept for particle tracing studies, flowing microparticles were visualized
      to inform the design of hydrogel constructs. Finally, the ability for mechanistic
      yet high-throughput screening was demonstrated in a vascular coculture model
      adopting endothelial and mesenchymal stem cells (HUVEC-MSC), encapsulated in
      gelatin-norbornene (gel-NOR) hydrogel cast into SLA-printed well inserts. This
      study illustrates the potential of a scalable dual perfusion bioreactor platform
      for parenchymal and barrier tissue constructs to support a broad range of multi
      organ-on-a-chip applications.

PMID- 30117515
TI  - A bioinspired structured graphene surface with tunable wetting and high wearable
      properties for efficient fog collection.
AB  - Inspired by the fog harvesting ability of the spider net and the interphase
      wetting surface of Namib desert beetles, we designed a kind of special
      bioinspired hybrid wetting surface on a Cu mesh by combining polydimethylsiloxane
      (PDMS) and graphene (G). A surface containing hydrophobic and superhydrophobic
      areas is prepared by a combination of laser etching and ultrasonic vibration.
      Thus, this as-prepared hybrid wetting surface can quickly drive tiny water
      droplets toward more wettable regions, which makes a great contribution to the
      improvement of collection efficiency. Moreover, the PDMS/G surface not only is
      tolerant to many stresses such as excellent anti-corrosion ability, anti-UV
      exposure and oil contamination, but also shows self-healing simply by burning the
      worn areas, which thus endows the surface with tunable-wettability change between
      flame treatment and abrasive wear. This study offers a novel insight into the
      design of burned healed materials with interphase wettability that may enhance
      the fog collection efficiency in engineering liquid harvesting equipment and
      realizes renewable materials in situ cheaply and rapidly by processes that can be
      easily scaled and automated.

PMID- 30117516
TI  - Spatial distribution of organic functional groups supported on mesoporous silica
      nanoparticles (2): a study by 1H triple-quantum fast-MAS solid-state NMR.
AB  - The distribution of organic functional groups attached to the surface of
      mesoporous silica nanoparticles (MSNs) via co-condensation was scrutinized using
      1D and 2D 1H solid-state NMR, including the triple-quantum/single-quantum (TQ/SQ)
      homonuclear correlation technique. The excellent sensitivity of 1H NMR and high
      resolution provided by fast magic angle spinning (MAS) allowed us to study
      surfaces with very low concentrations of aminopropyl functional groups. The
      sequential process, in which the injection of tetraethyl orthosilicate (TEOS)
      into the aqueous mother liquor was followed by dropwise addition of the
      organosilane precursor, resulted in deployment of organic groups on the surface,
      which were highly clustered even in a sample with a very low loading of ~0.1 mmol
      g-1. The underlying mechanism responsible for clustering could involve fast
      aggregation of the aminopropyltrimethoxysilane (APTMS) precursor within the
      liquid phase, and/or co-condensation of the silica-bound molecules. Understanding
      the deposition process and the resulting topology of surface functionalities with
      atomic-scale resolution, can help to develop novel approaches to the synthesis of
      complex inorganic-organic hybrid materials.

PMID- 30117517
TI  - A glucogalactomannan isolated from Agaricus bisporus induces apoptosis in
      macrophages through the JNK/Bim/caspase 3 pathway.
AB  - Agaricus bisporus is one of the most important edible and medicinal mushrooms in
      the world. It has been well known that Agaricus bisporus has an immunoregulatory
      role, but its active ingredients have not been completely identified. In this
      study, a glucogalactomannan named TJ3 was isolated and purified from Agaricus
      bisporus. TJ3 (827 kDa) is composed of mannose, galactose, glucose and xylose in
      the ratio 28.26 : 27.82 : 20.88 : 9.87 mainly joined by beta-linkages. Functional
      analysis of TJ3 revealed that it effectively induced apoptosis in RAW 264.7
      cells, a mouse macrophage cell line. Cell apoptosis was determined by an Annexin
      V/PI staining assay. After treatment with TJ3 (2 MUg mL-1) for 16 h, apoptosis
      was observed in 34% of the Raw cells (9% in the non-treated control cells). TJ3
      treatment remarkably increased the production of cleaved caspase-3, PARP and Bim,
      and decreased the level of Bcl-2 although no obvious change in the level of Bax
      was observed. Interestingly, further elucidation of the molecular mechanism
      underlying the role of TJ3 in the induction of apoptosis showed that TJ3
      activated the JNK signaling pathway through TLR4 and subsequently promoted the
      expression of Bim and activation of caspase-3. Our results demonstrate that TJ3
      may be a novel active component in Agaricus bisporus responsible for its
      immunoregulatory role by the induction of macrophage apoptosis.

PMID- 30117518
TI  - Sandwiched spherical tin dioxide/graphene with a three-dimensional interconnected
      closed pore structure for lithium storage.
AB  - Low reversion of lithium oxide (Li2O) and the tin (Sn) coarsening causing
      irreversible capacity loss is the main reason for the poor cycle performance in
      tin dioxide (SnO2) based composites. In this research, a novel sandwiched
      spherical tin dioxide/graphene with a three-dimensional interconnected closed
      pore structure is synthesized. The microstructural characterization shows that
      the spherical graphene with submicron sized diameters interconnects with each
      other forming an interconnected flexible conductive network, whereas a large
      number of SnO2 nanoparticles (approximately 5 nm) are limited homogeneously in
      between the interlayers of the sphere-like graphene shell. The sandwich structure
      of the SnO2/graphene and the closed graphene sphere can provide double protection
      for the SnO2. When it is used as an anode material for energy storage, the
      generated Li2O can remain in close contact with Sn to make the conversion
      reaction (SnO2 + 4Li+ + 2e- <-> Sn + Li2O) highly reversible in situ and the
      reversibility even does not diminish markedly after 100 cycles. A high reversible
      specific capacity of 914.8 mA h g-1 is expressed in the sandwiched spherical
      SnO2/graphene composite at 100 mA g-1 after 100 cycles, which is significantly
      higher than that of a SnO2/graphene aerogel with an open pore structure.

PMID- 30117519
TI  - Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in the Diagnosis
      of Hilar and Mediastinal Lymph Node Metastases of Melanoma.
AB  - OBJECTIVE: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS
      TBNA) is a minimally invasive technique for investigating hilar and mediastinal
      lymphadenopathy. This study reports eleven cases in which EBUS-TBNA was used to
      assess mediastinal and hilar lymph nodes for the presence of metastatic melanoma.
      MATERIAL AND METHOD: A retrospective study was performed of all patients who had
      a history of melanoma and underwent EBUS-TBNA to assess hilar or mediastinal
      lymphadenopathy for the presence of metastatic melanoma. In seven cases,
      molecular analysis to detect mutations in the BRAF gene was also used. RESULTS:
      Eight patients had been diagnosed with malignant melanoma in the past (mean 54.4
      months, range 18 to 115 months) while in the other three this tumor was primarily
      diagnosed in the staging phase. The male-female ratio was 6:5, and the mean age
      was 60.3 years (range 42 to 88 years). The mean hilar or mediastinal lymph node
      size detected with computed tomography was 3.0 cm (range 1.1 to 8.1 cm). Eight
      (72.7%) cases had metastases to the lung associated with metastases in the
      mediastinal lymph nodes. In four (50%) of these cases, the lung metastasis was
      solitary. Three (27.3%) cases had metastases in the mediastinal lymph nodes in
      absence of lung metastases. Metastatic melanoma was diagnosed by cytology and
      confirmed by cell block study with immunohistochemistry in all cases. BRAF
      mutations were detected in two (28.6%) of seven cases studied. CONCLUSION:
      Cytology and tissue samples obtained from EBUS-TBNA are adequate to detect
      metastatic melanoma and permit in some cases the determination of biomarkers and
      identify the presence or absence of mutations in the BRAF gene. The procedure is
      safe, fast, and precise for the staging of melanoma.

PMID- 30117520
TI  - [2018 ESC Guidelines for the diagnosis and management of syncope].

PMID- 30117521
TI  - The leads are still the weakest link.

PMID- 30117522
TI  - Renalase - a potential biomarker for risk of atrial fibrillation?

PMID- 30117523
TI  - Optimal timing for pulmonary valve replacement in asymptomatic patients after
      tetralogy of Fallot repair using cardiac magnetic resonance imaging.

PMID- 30117524
TI  - Constructivism in patient education: using drawings to explore preconception of
      coronary artery disease.

PMID- 30117525
TI  - Different Absorption Time of two Absorb BVS Implanted in the Same Artery:
      Insights into Mechanisms of Late Scaffold Failure.

PMID- 30117526
TI  - Cardiac involvement in lymphoma mimicking hypertrophic cardiomyopathy.

PMID- 30117527
TI  - Speckle tracking and global longitudinal strain in endomyocardial infiltration
      during FIP1L1-PDGFRA chronic eosinophilic leukaemia.

PMID- 30117528
TI  - Percutaneous angioplasty of the right and left main coronary and the left
      subclavian arteries in a patient with multilevel atherosclerosis.

PMID- 30117529
TI  - Sudden cardiac death in a young, male patient with rapidly progressing systemic
      sclerosis.

PMID- 30117530
TI  - Distal coronary artery wire perforation: a simple method for infrequent
      complication.

PMID- 30117531
TI  - National Program of Severe Growth Hormone Deficiency Treatment in Adults and
      Adolescents after Completion of Growth Promoting Therapy.
AB  - Growth hormone (GH) has been used in the treatment of short stature in children
      with GH deficiency (GHD) for 60 years, and for about 30 years also in the
      treatment of adults with GHD, in whom such treatment is carried out due to
      metabolic indications. In Poland, GH treatment is reimbursed only in children
      with GHD, while so far it has not been refunded in adults with GHD. There are two
      groups of adults (or adolescents after growth completion) with GHD, who require
      GH therapy: patients with GHD that occurred in childhood (childhood-onset GHD -
      CO-GHD) and patients with GHD acquired in adulthood (adulthood-onset GHD - AO
      GHD). This review presents a brief outline of the history of GH treatment in
      humans, the latest data on the causes and symptoms of GHD in adults, and the
      complications of untreated GHD. Current recommendations regarding diagnosis,
      treatment and monitoring of GH therapy in adults are also discussed. Moreover,
      the review paper presents the objectives, assumptions, and plans of
      implementation of the "National Treatment Program for Severe Growth Hormone
      Deficiency in Adults and Adolescents after Completion of the Growth Promoting
      Therapy", as well as the expected health and economic effects of introducing GH
      treatment in adults with GHD in Poland.

PMID- 30117533
TI  - Assessing the reproducibility of an O-glycopeptide enrichment method with a novel
      software, Pinnacle.
AB  - A novel software, Pinnacle was used to reassess the reproducibility of a 2-step
      lectin-based O-glycopeptide enrichment method. A publicly available dataset
      consisting of 12 data files representing 3 technical replicates of enriched
      glycopeptides from human serum was investigated. Previously, an attempt for
      reproducibility assessment was made utilizing an MS/MS scan (MS2)-based method.
      However, the stochastic nature of precursor ion selection strongly biased this
      approach leading to underestimated rate of reproducibility. To bypass this
      problem, our present method follows the general path to confidently identify O
      glycopeptides (database search with MS/MS data) supplemented with full
      scan/survey scan (MS1)/extracted ion chromatogram (XIC) mining in all files using
      two software packages, Pinnacle and Skyline. Confident MS/MS identifications were
      delivered by Protein Prospector. With this input Skyline indicated a 70%
      reproducibility for our workflow. However, Pinnacle performed better, indicating
      the presence of 90% of the confidently assigned glycopeptides in all the three
      replicates. Pinnacle, just like Skyline, performs ion extraction using the high
      accuracy, high resolution mass measurement data but it also utilizes all the
      available MS/MS spectra, even from different activation methods, within the same
      file to make mass spectrometric data evaluation for glycopeptides more reliable.

PMID- 30117532
TI  - Plasma adiponectin array in women with Alzheimer's disease.
AB  - Introduction Alzheimer's disease (AD) is a progressive and irreversible
      neurodegenerative disease. Typical features of AD include memory loss, social
      dysfunction and physical impairment. Although the pathological findings in the
      central nervous system are well established, the etiological factors are poorly
      known. Recent studies suggested the role of metabolic disturbances in the
      development of AD neurodegeneration. Adiponectin, an anti-inflammatory and
      metabolism regulating factor, was linked to AD. Aim The aim was to examine
      whether adiponectin fractions combined with insulin/insulin resistance-associated
      metabolic parameters correlate with AD progression. Material and methods The
      study comprised 98 women: 27 with moderate to severe AD, 31 with AD at early
      stage and 40 healthy controls, matched for age and BMI. To evaluate memory
      impairment, the MMSE was performed. Plasma total adiponectin and its high-,
      medium- and low molecular weights were measured with ELISA. Anthropometric,
      clinical and metabolic parameters were assessed. Correlations between adiponectin
      array and measured parameters were evaluated. Results In comparison to the
      controls, enhanced levels of total and medium molecular weight adiponectin
      characterized AD individuals. In AD, we found correlations between adiponectin
      array, and anthropometric and biochemical parameters. After adjustment to BMI, a
      significant increase of the total adiponectin and high- and medium molecular
      weight fractions was observed. A negative correlation between low molecular
      weight adiponectin and MMSE was found. Conclusions Our results indicate a
      possible link between adiponectin variations and AD. We hypothesize that changes
      in adiponectin profile observed in AD result from compensatory mechanism against
      neuropathological processes, as well as from adiponectin homeostasis impairment.

PMID- 30117534
TI  - Characterization of bacteriophage HN48 and its protective effects in Nile tilapia
      Oreochromis niloticus against Streptococcus agalactiae infections.
AB  - Streptococcus agalactiae is a causative agent responsible for massive mortalities
      of tilapia that has led to catastrophic losses to tilapia culture globally.
      Bacteriophages represent a new class of antimicrobials against bacteria. In this
      study, we characterized the bacteriophage HN48, which formed small and round
      transparent plaques on a double-layer plate. With a hexagonal head and a long
      tail, this phage may belong to the Caudovirales according to the International
      Committee on Taxonomy of Viruses. HN48 was found to have a relatively wide and
      highly specific host range, to be sensitive to high temperature (60-80 degrees C)
      and low pH (3-5), and to be relatively stable at alkaline pH (8-10).
      Intraperitoneal injection with HN48 had no adverse effects on tilapia and
      effectively inactivated the bacteria in the kidney. Fish that received phage
      therapy had 60% +/- 3.3% survival rates and a delayed mean death time of about 3
      days when compared to the control group. To the best of knowledge, this is the
      first study of tilapia streptococcal phage. Overall, the results indicated that
      phage HN48 could prevent tilapia from experimental S. agalactiae infection,
      suggesting it has the potential to control this disease.

PMID- 30117536
TI  - JPEN Journal Club 37. Placebos and Nocebos.

PMID- 30117535
TI  - Distinct branches of the N-end rule pathway modulate the plant immune response.
AB  - The N-end rule pathway is a highly conserved constituent of the ubiquitin
      proteasome system, yet little is known about its biological roles. Here we
      explored the role of the N-end rule pathway in the plant immune response. We
      investigated the genetic influences of components of the pathway and known
      protein substrates on physiological, biochemical and metabolic responses to
      pathogen infection. We show that the glutamine (Gln) deamidation and cysteine
      (Cys) oxidation branches are both components of the plant immune system, through
      the E3 ligase PROTEOLYSIS (PRT)6. In Arabidopsis thaliana Gln-specific amino
      terminal (Nt)-amidase (NTAQ1) controls the expression of specific defence
      response genes, activates the synthesis pathway for the phytoalexin camalexin and
      influences basal resistance to the hemibiotroph pathogen Pseudomonas syringae pv
      tomato (Pst). The Nt-Cys ETHYLENE RESPONSE FACTOR VII transcription factor
      substrates enhance pathogen-induced stomatal closure. Transgenic barley with
      reduced HvPRT6 expression showed enhanced resistance to Ps. japonica and Blumeria
      graminis f. sp. hordei, indicating a conserved role of the pathway. We propose
      that that separate branches of the N-end rule pathway act as distinct components
      of the plant immune response in flowering plants.

PMID- 30117537
TI  - Microbial community of nitrogen cycle-related genes in aquatic plant rhizospheres
      of Lake Liangzi in winter.
AB  - This study investigated the community structure of ammonia-oxidizing bacteria
      /archaea (AOB and AOA), as well as the effects of four aquatic plants (namely
      Ceratophyllum demersum, Hydrilla verticillata, Potamogeton crispus, and Nymphaea
      tetragona) rhizospheres on the abundance of AOB amoA, AOA amoA, anammox 16S rRNA,
      nirK, and nirS in Lake Liangzi, China. Phylogenetic analysis revealed that most
      AOB groups were Nitrosospira and Nitrosomonas, in which Nitrosospira was
      dominant. The AOA amoA were affiliated with two branches of classical sequences
      which belonging to Thaumarchaeota: water/sediments branch and soil/sediments
      branch. The abundance of AOA amoA in the rhizospheres of aquatic plants were
      higher than in the non-rhizosphere (p < 0.05), indicating that aquatic plants may
      promote the growth of AOA. However, the anammox 16S rRNA showed the opposite
      trend relative to AOA amoA (p < 0.05). Redundancy analysis (RDA) showed that the
      differences in abundance of AOB, AOA, anammox bacteria, and denitrifying bacteria
      are very likely related to the different contents of ammonia nitrogen (NH4 + -N),
      pH and dissolved oxygen (DO) and thus to the rhizosphere states of aquatic
      plants.

PMID- 30117538
TI  - Linking variation in intrinsic water-use efficiency to isohydricity: a comparison
      at multiple spatiotemporal scales.
AB  - Species-specific responses of plant intrinsic water-use efficiency (iWUE) to
      multiple environmental drivers associated with climate change, including soil
      moisture (theta), vapor pressure deficit (D), and atmospheric CO2 concentration
      (ca ), are poorly understood. We assessed how the iWUE and growth of several
      species of deciduous trees that span a gradient of isohydric to anisohydric water
      use strategies respond to key environmental drivers (theta, D and ca ). iWUE was
      calculated for individual tree species using leaf-level gas exchange and tree
      ring delta13 C in wood measurements, and for the whole forest using the eddy
      covariance method. The iWUE of the isohydric species was generally more sensitive
      to environmental change than the anisohydric species was, and increased
      significantly with rising D during the periods of water stress. At longer
      timescales, the influence of ca was pronounced for isohydric tulip poplar but not
      for others. Trees' physiological responses to changing environmental drivers can
      be interpreted differently depending on the observational scale. Care should be
      also taken in interpreting observed or modeled trends in iWUE that do not
      explicitly account for the influence of D.

PMID- 30117539
TI  - "I Just Kept It to Myself": The Shaping of Latina Suicidality Through Gendered
      Oppression, Silence, and Violence.
AB  - Suicide is a critical issue among Latina youth. In this study, we use family case
      analysis to explore how gendered oppression, silencing, and violence shape
      suicidal behaviors among a sample of Latina daughters (n = 10), and their
      parents. For comparison, we include family narratives from Latina adolescents
      with no histories of suicide attempts (n = 10). Results suggest how secrets and
      silence, as indicative of gendered oppression, may catalyze a suicide attempt.
      The risks are particularly salient when daughter and mother both have experienced
      violence that conflicts with gendered cultural scripts. Findings highlight the
      importance of parental engagement and exploration of histories of violence in the
      treatment of Latina suicide attempters. Future research should incorporate the
      risk factors of gendered oppression and violence to better understand the
      development of suicidality among Latina women.

PMID- 30117541
TI  - The Hazards of Distraction: Ticking All the EHR Boxes.

PMID- 30117540
TI  - Synthetic colloid fluids (6% hydroxyethyl starch 130/0.4 and 4% succinylated
      gelatin) interfere with total plasma protein measurements in vitro.
AB  - BACKGROUND: High molecular weight (MW) synthetic colloids interfere with
      refractometry. The effect of low MW synthetic colloids on refractometry is
      unknown. OBJECTIVES: To investigate the effect of 6% hydroxyethyl starch 130/0.4
      (HES) and 4% succinylated gelatin (GELO) on the refractometric measurement of
      total plasma protein (TPP) and colloid osmotic pressure (COP) in canine plasma.
      METHODS: Heparinized plasma from 10 dogs was diluted with 0.9% saline (NaCl),
      HES, and GELO in ratios of plasma:fluid, 9:1, 8:2, 7:3, 6:4, and 5:5. The biuret
      TPP (TPPb), refractometric TPP (TPPr), and COP assays were performed for all
      dilutions. Agreement (bias, 95% limits of agreement (LOA)) was tested between the
      TPPb (NaCl) and the TPPr of the NaCl, HES, and GELO plasma dilutions, and between
      the TPPb (NaCl) and the TPPb of the HES and GELO plasma dilutions. RESULTS: A
      small bias (0.06 g/dL, 95% LOA -0.51 to 0.39 g/dL) existed between TPPb (NaCl)
      and TPPr (NaCl). A large bias was found between TPPb (NaCl) and TPPr (HES) (1.38
      g/dL, 95% LOA 0.30 to 3.10 g/dL), and TPPr (GELO) (1.18 g/dL, 95% LOA 0.53 to
      2.88 g/dL). A small bias was found between TPPb (NaCl) and TPPb (HES) (0.08 g/dL,
      95% LOA -2.04 to 2.20 g/dL), and a large bias was found between TPPb (NaCl) and
      TPPb (GELO) (1.00 g/dL, 95% LOA -0.59 to 2.60 g/dL). Increasing overestimation of
      TPPb (NaCl) by TPPr (HES and GELO) and TPPb (GELO) occurred with increasing
      colloid volumes. CONCLUSIONS: HES and GELO interfered with TPPr, and GELO also
      interfered with TPPb, in vitro. These variables should be interpreted with
      caution for dogs that have received these synthetic colloids.

PMID- 30117543
TI  - Guideline for sterilization.

PMID- 30117542
TI  - Guideline Implementation: Team Communication: 1.8
      www.aornjournal.org/content/cme.
AB  - The perioperative environment is fast paced and complex. Competing
      responsibilities, noise and distractions, and reluctance of team members to speak
      up when they are aware of a potential patient safety issue are all barriers to
      effective communication in the perioperative setting. Communication breakdowns
      among health care providers can lead to medical errors and patient harm. Accurate
      and complete communication about the patient and the patient's care can
      contribute to improved efficiency, better patient outcomes, and fewer adverse
      events. The new AORN "Guideline for team communication" provides guidance on
      using standardized processes and tools to improve the quality of team
      communication. The key points address hand overs between phases of perioperative
      care; a briefing to share the surgical plan; a time out to verify the correct
      patient, procedure, site, and side; and a debriefing to discuss what was learned
      and how to improve. Perioperative RNs should review the complete guideline for
      additional information and for guidance when writing and updating policies and
      procedures.

PMID- 30117547
TI  - Succession Planning and the Future of Perioperative Nursing Leadership.

PMID- 30117545
TI  - Preparing Novice Perioperative Nurses Using the QSEN Methodology.

PMID- 30117544
TI  - Care of the Patient Undergoing a Neurosurgical Procedure in an Intraoperative
      Magnetic Resonance Imaging Suite.
AB  - The intraoperative nursing care of a patient undergoing a neurosurgical procedure
      in an intraoperative magnetic resonance imaging (MRI) suite requires an elevated
      level of planning and implementation of interventions for patient safety and the
      safety of the surgical team. Developing team guidelines, protocols, and
      competencies that take into account the specific safety and positioning
      requirements for an MRI scan (ie, identifying MRI zones, safe use of ferrous and
      nonferrous instruments, following MRI safety guidelines) is key to the success of
      these procedures. Personnel at two sites at the University of Utah Health in Salt
      Lake City have implemented a standardized intraoperative MRI program for a
      variety of neurosurgical procedures.

PMID- 30117548
TI  - Reducing environmental effects in health care.

PMID- 30117549
TI  - Mechanical thrombectomy for ischemic stroke.

PMID- 30117550
TI  - Knowledge, Accuracy, Precision: Requirements for the Perioperative Neurosurgical
      Nurse.

PMID- 30117551
TI  - Patient Care During Minimally Invasive Lateral Spine Surgery: 1.7
      www.aornjournal.org/content/cme.
AB  - Perioperative nurses care for patients undergoing a wide range of surgical
      procedures. One fast-growing surgical specialty is spine surgery performed using
      minimally invasive techniques. Patients may be candidates for minimally invasive
      spine surgery based on their presenting signs and symptoms and medical imaging
      test results. Open anterior and posterior surgical approaches to spine surgery
      are how surgeons traditionally have performed these procedures. However, new
      technology has enabled a minimally invasive lateral approach to the spine. This
      approach minimizes many of the risks and challenges associated with both the
      anterior and posterior approaches. Minimally invasive lateral interbody fusion
      requires the perioperative nurse to have a thorough understanding of the
      necessary patient positioning, spinal anatomy, and OR suite setup to ensure a
      safe and successful surgical experience for the patient.

PMID- 30117552
TI  - Did You Know?

PMID- 30117554
TI  - Guideline Summary: Team Communication.

PMID- 30117553
TI  - Perioperative Care of the Patient With Acoustic Neuroma.
AB  - Acoustic neuromas, also known as vestibular schwannomas, are slow-growing, benign
      tumors that develop on the eighth cranial nerve. Common signs and symptoms of an
      acoustic neuroma include hearing loss and balance disturbances. A physical
      examination, a hearing evaluation, and diagnostic imaging assist in the diagnosis
      of an acoustic neuroma. Patients with a confirmed tumor have three treatment
      options: observation, stereotactic radiosurgery, and surgical removal.
      Complications include cerebrospinal fluid leakage, damage to ancillary brain
      structures, facial nerve damage, and bleeding or vascular injury. This article
      focuses on the surgical removal of an acoustic neuroma and the role of the
      perioperative nurse in the perioperative care of the patient.

PMID- 30117555
TI  - The Key to Safety: A Healthy Workplace.

PMID- 30117557
TI  - Guideline Quick View: Safe Patient Handling and Movement.

PMID- 30117556
TI  - Avoiding surgical site infections: guidelines and collaboration.

PMID- 30117558
TI  - Evidence appraisal of Fox NS, Melka S, Miller J, et al. Suture compared with
      staple closure of skin incision for high-order cesarean deliveries. Obstet
      Gynecol. 2018;131(3):523-528.

PMID- 30117559
TI  - Clinical Issues-August 2018: 1.6 www.aornjournal.org/content/cme.

PMID- 30117560
TI  - Total gastrectomy with Roux-en-Y anastomosis.

PMID- 30117561
TI  - Perioperative Care During Deep Brain Stimulation Surgery.
AB  - Deep brain stimulation (DBS) is a life-changing surgical treatment. More than
      150,000 patients worldwide have been treated with DBS, primarily for Parkinson
      disease and medically refractory tremor and dystonia. However, the use of DBS has
      recently expanded beyond traditional movement disorders to include the treatment
      of obsessive compulsive disorder, epilepsy, and other neurological and
      psychological diseases. Considering this expanded use of DBS, it is essential to
      understand the role that each member of the multidisciplinary health care team
      plays and how to avoid possible complications during this procedure. Proper
      patient selection, precise anatomical placement of the electrode, and proper
      programming of the implanted device are key aspects of DBS treatment. It also is
      valuable to understand how the deep brain stimulator is implanted and functions.
      Accurate lead placement that results in positive outcomes for patients relies on
      collaboration from an experienced perioperative team led by the neurosurgeon.

PMID- 30117562
TI  - 2018 Conference Poster Collection.

PMID- 30117564
TI  - The current status of avian aspergillosis diagnoses: Veterinary practice to novel
      research avenues.
AB  - Aspergillus fungal infections continue to be a significant cause of morbidity and
      mortality in birds that can, in part, be attributed to the lack of a diagnostic
      "gold standard" for Aspergillus infection, and which delays the diagnosis,
      treatment, and outcome of avian patients. At present, none of the available
      methods in veterinary care can detect aspergillosis early enough and with the
      accuracy, precision, and specificity required of an ideal diagnostic tool.
      Therefore, researching methods of Aspergillus detection is still an active area
      of inquiry, and novel techniques continue to emerge. This review will provide a
      brief overview of current clinical methods, with an emphasis on avian care, in
      addition to a series of techniques in development that could offer distinct
      advantages over existing methods.

PMID- 30117565
TI  - Migraine and cerebrovascular diseases: Epidemiology, pathophysiological, and
      clinical considerations.
AB  - Migraine and cerebrovascular diseases are disabling disorders, which are possibly
      closely interrelated. Heterogeneous and scattered evidence in literature remains
      a challenge. We searched for systematic reviews including diverse cerebrovascular
      events in migraineurs and reported relevant original studies to update the
      evidence when necessary. The studies show that migraine is associated with
      increased risk of transient ischemic attacks, any stroke, and possibly
      hemorrhagic stroke. In addition, migraine with aura increases the risk of
      ischemic stroke and white matter abnormalities. Migraine without aura increases
      the risk of cervical artery dissection as a cause of ischemic stroke. Groups with
      specific risk profiles are women, young people, smokers, and oral contraceptive
      users. The pathophysiology of the association remains uncertain. However, genetic
      and environmental factors may be involved in intricate mechanisms responsible for
      oxidative stress, vascular dysfunction and, ultimately, vascular events. In
      conclusion, migraine is a potential risk factor for cerebrovascular diseases.
      Migraineurs should be carefully evaluated considering their vascular risk
      assessment based on current evidence, so that healthcare professionals can
      provide appropriate and individualized management of other cardiovascular risk
      factors, notably quitting smoking and restricting use of oral contraceptives.

PMID- 30117566
TI  - Spatial and temporal variability of myxozoan parasite, Myxobolus inornatus,
      prevalence in young of the year smallmouth bass in the Susquehanna River Basin,
      Pennsylvania.
AB  - A myxozoan parasite, Myxobolus inornatus, is one disease agent identified in
      young of the year (YOY) smallmouth bass in the Susquehanna River Basin,
      Pennsylvania. We investigated spatial and temporal variability in M. Inornatus
      prevalence across the Susquehanna River Basin and at several out-of-basin sites.
      We examined potential land use drivers of M. Inornatus prevalence including
      agricultural and developed land use. In 1,267 YOY smallmouth bass collected from
      32 sites during 2013-2016, M. Inornatus was documented in 43.6% of samples. Among
      site variability in parasite prevalence was greater than among-year variability.
      The effect of agricultural land use on M. Inornatus prevalence had a high
      probability of being positively correlated at multiple spatial scales
      (probability of positive effect > 0.80). The effect of developed land use on M.
      Inornatus prevalence had a relatively high probability of being negatively
      correlated at multiple spatial scales (probability of negative effect > 0.70).
      Our results suggest that land use practices could be related to M. Inornatus
      infection of smallmouth bass. Further study will be necessary to determine
      whether disease dynamics are a consequence of effects on the host, alterations of
      instream habitat mediating invertebrate host dynamics and/or survival and
      dispersal of the parasite infective stage.

PMID- 30117567
TI  - Correction.

PMID- 30117568
TI  - Hepatology Highlights.

PMID- 30117569
TI  - Erratum.

PMID- 30117570
TI  - Erratum.

PMID- 30117571
TI  - Front-of-neck access technique and scalpels.

PMID- 30117572
TI  - Are bougies gaining favour in videolaryngoscopy?

PMID- 30117573
TI  - 'Trachy Tracey' - an education tool for tracheostomy training.

PMID- 30117574
TI  - An indication for a throat pack?

PMID- 30117575
TI  - Does apnoeic oxygenation during rapid sequence induction prolong the procedure,
      or increase patient safety? A reply.

PMID- 30117576
TI  - Supraglottic check of tracheal tube position after fibreoptic intubation.

PMID- 30117577
TI  - Videolaryngoscopy using the Frova introducer. A reply.

PMID- 30117578
TI  - A frail future.

PMID- 30117579
TI  - An indication for a throat pack? A reply.

PMID- 30117580
TI  - Does apnoeic oxygenation during rapid sequence induction prolong the procedure,
      or increase patient safety?

PMID- 30117581
TI  - A lateral approach to ultrasound-guided sacral plexus block in the supine
      position.

PMID- 30117582
TI  - Difficult Airway Society guidelines on the airway management of critically ill
      patients. A reply.

PMID- 30117583
TI  - Is the C-MAC videolaryngoscope plus Frova introducer suitable for intubating the
      trachea of every patient?

PMID- 30117584
TI  - Radio-opacity of throat packs.

PMID- 30117585
TI  - DAS guidelines on the airway management of critically ill patients.

PMID- 30117587
TI  - Heart Replacement Therapy: Biological, Mechanical or Regenerative?

PMID- 30117592
TI  - Lipid Lowering Therapy for Atherosclerotic Cardiovascular Disease: It Is Not So
      Simple.
AB  - Plasma levels of atherogenic lipoproteins reflect a key risk factor for
      atherosclerotic cardiovascular disease ASCVD and treatments that lower these
      lipoproteins improve CV outcomes. Statins and PCSK9 inhibitors reduce LDL-C
      remarkably to low levels but do not eliminate residual cardiovascular risk as a
      result of other atherogenic lipoproteins or pathways for ASCVD, including
      inflammation, that are independent of LDL-C. Statins and PCSK9 inhibitors have
      complex mechanisms of action which appear to be additive and hence beneficial.
      Statin-intolerant subjects may benefit from ezetimibe, combination nutraceuticals
      and other drugs in development, while subjects with low LDL-C levels may benefit
      from anti-inflammatory drugs that target specific pathways. The future of
      pharmacotherapy for ASCVD will rely on a combination of drugs that reduce LDL-C
      and other atherogenic lipoproteins and drugs that target pathways including
      inflammation, endothelial function, vascular stiffness and anti-oxidant activity.

PMID- 30117586
TI  - Driving After Left Ventricular Assist Device Implantation.
AB  - Literature on driving capacities of ventricular assist device patients is rare
      and driving restrictions differ from center to center. Currently, no guidelines
      exist on whether and when left ventricular assist device (LVAD) patients are
      allowed to begin driving cars after device implantation. In this study, we assess
      the driving abilities of patients after LVAD implantation. Three hundred and
      ninety LVAD patients have been surveyed in a worldwide, multicenter study. The
      single survey followed a multi-method design, including online, phone, and face
      to-face interviews. Out of 390 patients, 72% are still driving and 28% did not
      continue driving after LVAD implantation. Reasons for discontinuation were
      capability (24%), insecurity (17%), and disapproval by family members (9%) or
      doctors (5%). Ninety percent of the patients describe their ability to drive as
      perfect or adequate. Sixty-nine percent state that they are not restricted in
      their general driving capacity. Forty-nine percent report not to be restricted in
      agility to drive by the device equipment. The majority of patients have not been
      involved in car accidents or major complications (94%). Eight accidents were
      reported (3%). Out of those, all were minor collisions. No patient reported the
      occurrence of a fatal accident or casualties. LVAD alarms did occur in six
      incidents (2%) with the majority being low battery alarms. The results of this
      study suggest that driving with a left ventricular assist device is safe for
      stable patients and driving can be resumed 3 months after LVAD implantation after
      careful patient assessment.

PMID- 30117593
TI  - Quantitative analysis of the dose-response of white spot syndrome virus in
      shrimp.
AB  - White spot syndrome virus (WSSV) is an important cause of mortality and economic
      losses in shrimp farming. Although WSSV-induced mortality is virus dose dependent
      and WSSV infection does not necessarily lead to mortality, the relationships
      between virus-particle dose, infection and mortality have not been analysed
      quantitatively. Here, we explored WSSV dose-response by a combination of
      experiments, modelling and meta-analysis. We performed dose-response experiments
      in Penaeus vannamei postlarvae, recorded host mortality and detected WSSV
      infection. When we fitted infection models to these data, two models-differing in
      whether they incorporated heterogeneous host susceptibility to the virus or not
      were supported for two independent experiments. To determine the generality of
      these results, we reanalysed published data sets and then performed a meta
      analysis. We found that WSSV dose-response kinetics is indeed variable over
      experiments. We could not clearly identify which specific infection model has the
      most support by meta-analysis, but we argue that these results also are most
      concordant with a model incorporating varying levels of heterogeneous host
      susceptibility to WSSV. We have identified suitable models for analysing WSSV
      dose-response, which can elucidate the most basic virus-host interactions and
      help to avoid underestimating WSSV infection at low virus doses.

PMID- 30117594
TI  - Recommendations for the use of telemedicine in severely under-resourced settings:
      results from a pilot study in Niamey, Niger.

PMID- 30117596
TI  - First Person: David Sidransky, MD: Clinician-Scientist Transforms Cancer Early
      Detection.

PMID- 30117595
TI  - A challenging case of pelvic inflammatory disease due to miliary tuberculosis.

PMID- 30117597
TI  - Scientists Find Link Between Cancer and Highly Processed Foods.

PMID- 30117598
TI  - Erratum: Dudley B, Karloski E, Monzon FA, et al. Germline mutation prevalence in
      individuals with pancreatic cancer and a history of previous malignancy. Cancer.
      2018;124:1691-1700.

PMID- 30117599
TI  - Untreated Depression Common in Caregiving Spouses of Patients With Cancer.

PMID- 30117600
TI  - Zoon's plasma cell balanitis: clinical and dermoscopic features in pediatric
      patients.

PMID- 30117601
TI  - Emodin suppresses activation of hepatic stellate cells through p38 mitogen
      activated protein kinase and Smad signaling pathways in vitro.
AB  - The aim of this study was to evaluate the hypothesis that emodin inhibits
      extracellular matrix (ECM)-related gene expression in activated hepatic stellate
      cells (HSCs) by blocking canonical or/and noncanonical components of transforming
      growth factor beta1 (TGFbeta1) intracellular signaling. Here, we demonstrate that
      emodin suppressed the gene expression of HSCs activation markers type I collagen,
      fibronectin, and alpha-smooth muscle actin, as well as HSCs proliferation.
      Mechanistically, emodin suppresses TGFbeta1, TGFbeta receptor II, TGFbeta
      receptor I, and Smad4 gene expression, as well as Smad luciferase activity.
      Simultaneously, emodin reduced p38 mitogen-activated protein kinase (p38MAPK )
      activity but not c-Jun N-terminal kinases and extracellular signal-regulated
      kinases 1 and 2 phosphorylation in HSC-T6 cells. Interestingly, deprivation of
      TGFbeta using a neutralizing antibody abolished emodin-mediated inhibitions of
      the both Smad transcriptional activity and p38MAPK phosphorylation. Furthermore,
      emodin-mediated inhibition of HSCs activation could be partially blocked by
      PD98059 inhibition of p38MAPK or short hairpin RNA-imposed knockdown of Smad4.
      Conversely, simultaneous inhibition of Smad4 and p38MAPK pathways completely
      reverses the effects of emodin, suggesting that Smad and p38MAPK locate
      downstream of TGFbeta1 and regulate collagen genes expression in HSCs.
      Collectively, these data suggest that emodin is a promising candidate for the
      treatment of hepatic fibrosis.

PMID- 30117602
TI  - Photocatalytic Hydrogen Evolution by a Synthetic [FeFe] Hydrogenase Mimic
      Encapsulated in a Porphyrin Cage.
AB  - The design of a biomimetic and fully base metal photocatalytic system for
      photocatalytic proton reduction in a homogeneous medium is described. A synthetic
      pyridylphosphole-appended [FeFe] hydrogenase mimic was encapsulated inside a
      supramolecular zinc porphyrin-based metal-organic cage structure Fe4 (Zn-L)6 .
      The binding is driven by the selective pyridine-zinc porphyrin interaction and
      results in the catalyst being bound strongly inside the hydrophobic cavity of the
      cage. Excitation of the capsule-forming porphyrin ligands with visible light
      while probing the IR spectrum confirmed that electron transfer takes place from
      the excited porphyrin cage to the catalyst residing inside the capsule. Light
      driven proton reduction was achieved by irradiation of an acidic solution of the
      caged catalyst with visible light.

PMID- 30117603
TI  - Production of IL-35 by Bregs is mediated through binding of BATF-IRF-4-IRF-8
      complex to il12a and ebi3 promoter elements.
AB  - IL-10 and IL-35 suppress excessive immune responses and therapeutic strategies
      are being developed to increase their levels in autoimmune diseases. In this
      study, we sought to identify major cell types that produce both cytokines in-vivo
      and to characterize mechanisms that regulate their production. Experimental
      autoimmune uveitis (EAU) is a CNS autoimmune disease that serves as model of
      human uveitis. We induced EAU in C57BL/6J mice and investigated whether T cells,
      B lymphocytes, or myeloid cells are the major producers of IL-10 or IL-35 in
      blood, lymph nodes (LNs), spleen, and at the site of ocular inflammation, the
      neuroretina. Analysis of these tissues identified B cells as the major producers
      of IL-10 and IL-35 in-vivo. Compared to regulatory T cells (Tregs), IL-10- or IL
      35-producing regulatory B cells (Bregs) are substantially expanded in blood, LNs,
      spleen, and retina of mice with EAU. We performed EMSA and chromatin
      immunoprecipitation (ChIP) assays on activated B cells stimulated with IL-35 or
      TLR agonists. We found that BATF, IFN regulatory factor (IRF)-4, and IRF-8
      transcription factors were recruited and bound to AP1-IRF-composite elements
      (AICEs) of il12a, ebi3, and/or il10 loci, suggesting their involvement in
      regulating IL-10 and IL-35 transcriptional programs of B cells. Showing that B
      cells are major source of IL-10 and IL-35 in-vivo and identifying transcription
      factors that contribute to IL-10 and IL-35 expression in the activated B-cell,
      suggest that the BATF/IRF-4/IRF-8 axis can be exploited therapeutically to
      regulate physiological levels of IL-10/IL-35-Bregs and that adoptive transfer of
      autologous Bregs might be an effective therapy for autoimmune and
      neurodegenerative diseases.

PMID- 30117604
TI  - Comparative performance of growth, vertebral structure and muscle composition in
      diploid and triploid Paralichthys olivaceus.
AB  - Growth, skeletal structure and muscle composition of cold-shock-induced triploid
      olive flounder Paralichthys olivaceus were investigated. The average values of
      total length and total weight of triploids were higher than those of diploids
      from 5 to 11 months posthatch (mph). The growth difference disappeared after 11
      mph. The skeletal structure of flounder at 11 mph was observed by X-ray imaging
      method. There are four kinds of vertebral deformity including vertebrae fusion,
      one-sided compression, two-sided compression and vertically shifted. The trunk
      region (V8-18) and tailing end of the vertebral column were the predominant
      locations of deformity. In general, the frequencies of vertebral deformities in
      triploids (60.0%) were higher than those in diploids (33.3%, p < 0.05). Both the
      number of fish with deformed vertebrae and the average frequencies of deformed
      vertebrae in triploids were significantly higher than those in diploids (p <
      0.05). The muscle tissues of diploid and triploid flounder at 11 mph contain the
      same types of fatty acid and free amino acid profiles. The number of fatty acids
      with significant higher contents in diploids and triploids was one and ten,
      respectively (p < 0.05). The contents of free amino acids showed no difference
      between triploid and diploid fish.

PMID- 30117606
TI  - A morphological study of the male reproductive tract, post-testicular acrosome
      maturation and spermatophore formation in the black tiger prawn (Penaeus
      monodon).
AB  - Inferior larval production rates of domesticated Penaeus monodon broodstock has
      been a major hurdle to the expansion of its aquaculture, so that a better
      understanding of basic male reproductive biology is critical to improve the
      reproductive performance of this commercially important penaeid species.
      Following our previous study of spermatogenesis in the species, this study
      explored the mechanism of spermatophore formation with regards to the
      contribution of the reproductive tract epithelium by light and transmission
      electron microscopy. Four types of epithelial secretions (S1-4) were observed
      contributing to the three layers of the spermatophore. The primary layer of
      spermatophore was composed of S1 and S2, which were released from the secretory
      epithelial cells of the proximal vas deferens (PVD) and the secretory epithelial
      cells of the sperm-bearing lumen of the mid vas deferens, respectively. The
      secondary layer of the spermatophore was composed of S3, the secretory product of
      epithelial cells in the accessory tubule lumen of the mid vas deferens. The outer
      layer of the spermatophore was formed from S4 which was secreted by the
      epithelial cells in the posterior mid vas deferens and the terminal ampulla.
      Unique folds of the vas deferens epithelium appeared to play an important role in
      the formation of the spermatophore, particularly in the formation of the
      laminated structure of the spermatophore appendage. With respect to acrosome
      maturation along the reproductive tract, most spermatozoa did not have a fully
      developed anterior spike and a subacrosomal region when in the PVD, whereas both
      structures were fully formed by the time the spermatozoa reached the mid vas
      deferens and increased electron density when in the terminal ampulla; this
      observation represents the first morphological evidence of post-testicular
      acrosome maturation in this taxon.

PMID- 30117605
TI  - Changes in biomechanical knee injury risk factors across two collegiate soccer
      seasons using the 11+ prevention program.
AB  - The 11+ injury prevention program effectively reduces injuries in high school
      aged female soccer player, but the mechanism of the 11+ is unknown, particularly
      whether it impacts biomechanical risk factors associated with knee injuries. The
      purpose of this study was to report the changes in hip and knee biomechanics with
      use of the 11+ over two soccer seasons. Two collegiate women's soccer teams
      performed the 11+ for two soccer seasons. A control team was followed for one
      season. Athletes performed motion analysis of a drop vertical jump during
      preseason and postseason. Both groups had meaningful increases in peak knee
      abduction angle over the first season, and there were no meaningful changes in
      peak knee abduction moment over either season. The control group had bilateral
      decreases in knee flexion angle. The program did not seem to systematically
      impact biomechanical risk factors associated with knee injuries, with increases
      in peak knee abduction angle and no bilateral changes in frontal or transverse
      hip motion. The 11+ may have mitigated clinically meaningful decreases in knee
      flexion; however, as ACL injuries do not occur purely in the sagittal plane, it
      is unclear the impact of these changes. The results of this study indicate that
      the 11+ may require some modifications to impact landing biomechanics and
      potentially risky movement patterns, particularly when used in collegiate women
      over multiple seasons.

PMID- 30117607
TI  - One skull to rule them all? Descriptive and comparative anatomy of the
      masticatory apparatus in five mouse species.
AB  - Murine rodents display a unique cranial morphology and masticatory musculature.
      Yet detailed myological descriptions are scarce, especially considering the great
      diversity of the subfamily and the use of the house mouse and brown rat as model
      organisms. The masticatory musculature in these two species has been thoroughly
      described, which allows comparisons with other wild species. Description and
      comparison of a wide range of species constitutes a necessary step to fully
      understand how ecological factors may influence the morphology and myology of the
      skull in the Murinae and vice versa. In this study, we describe the masticatory
      musculature of five mouse species: Mus caroli, Mus cervicolor, Mus pahari, Mus
      fragilicauda, and Mus minutoides. For each species, one to five specimens were
      dissected, and their muscle weights and volumes calculated. One specimen was
      selected for iodine-enhanced CT-scanning, which allowed us to digitally
      reconstruct the musculature. We then compared the different masticatory
      arrangements between these species, as well as with the previous descriptions of
      the house mouse and brown rat. We show that interspecific differences especially
      involved the temporalis muscle and zygomatico-mandibularis muscular groups,
      although some differences were also seen in the pterygoid muscle and masseter
      muscle groups. We then propose some ecological interpretations for these
      differences, by interpreting them in terms of functional differences.

PMID- 30117608
TI  - Childhood adversity, health and quality of life in adults with intellectual and
      developmental disabilities.
AB  - BACKGROUND: Associations between childhood adversity and negative health outcomes
      are well documented within the general population; however, this relationship has
      yet to be confirmed in adults with intellectual and developmental disabilities
      (I/DD). Bridging the gap between public health and I/DD research is critical in
      order to better understand the ways in which the health of people with I/DD are
      compromised by adversity and social disadvantage and to develop preventative care
      frameworks and health-promoting practices specifically for adults with I/DD. The
      aim of this exploratory study was to examine the relationships among adversity,
      physical health and quality of life in a sample of adults with I/DD. METHOD:
      Participants were adults with I/DD currently residing within campus-based
      residences. Demographic data, psychiatric and medical diagnoses, adverse
      childhood experiences scores and quality of life scores were aggregated from
      participants' electronic medical records. A health history form was completed for
      each participant based on a review of participants' medical records. RESULTS:
      Results indicated childhood adversity was significantly associated with number of
      chronic medical conditions (r = .35, P < .001, 95% BCa CI [.13, .53]). Childhood
      adversity was not significantly related to quality of life. After controlling for
      demographic variables, childhood adversity remained a significant predictor of
      health history (B = .32, P < .005, 95% BCa CI [.10, .52]), with greater adversity
      predicting greater medical illness. CONCLUSION: Participants demonstrated higher
      rates of childhood adversity compared with the general population, suggesting
      that individuals with I/DD may be particularly vulnerable to experiencing
      adversity during development. Childhood adversity was a significant predictor of
      physical illness in adults with I/DD. These findings emphasise the importance of
      screening for childhood adversity histories in adults with I/DD. Additionally,
      results demonstrate the importance of offering preventative interventions geared
      at preventing physical illness and promoting health in adults with I/DD with
      adversity and trauma backgrounds.

PMID- 30117609
TI  - NCOR1-a new player on the field of T cell development.
AB  - Nuclear receptor corepressor 1 (NCOR1) is a transcriptional corepressor that
      links chromatin-modifying enzymes with gene-specific transcription factors.
      Although identified more than 20 years ago as a corepressor of nuclear receptors,
      the role of NCOR1 in T cells remained only poorly understood. However, recent
      studies indicate that the survival of developing thymocytes is regulated by
      NCOR1, revealing an essential role for NCOR1 in the T cell lineage. In this
      review, we will briefly summarize basic facts about NCOR1 structure and
      functions. We will further summarize studies demonstrating an essential role for
      NCOR1 in controlling positive and negative selection of thymocytes during T cell
      development. Finally, we will discuss similarities and differences between the
      phenotypes of mice with a T cell-specific deletion of NCOR1 or histone
      deacetylase 3 (HDAC3), because HDAC3 is the predominant member of the HDAC family
      that interacts with NCOR1 corepressor complexes. With this review we aim to
      introduce NCOR1 as a new player in the team of transcriptional coregulators that
      control T cell development and thus the generation of the peripheral T cell pool.

PMID- 30117610
TI  - Growth and cranial development in the Andean frogs of the genus Telmatobius
      (Anura: Telmatobiidae): Exploring the relation of heterochrony and skeletal
      diversity.
AB  - Andean frogs of the genus Telmatobius occur at high elevations, they have an
      aquatic mode of life and large tadpoles. There are more than 60 species that
      closely resemble one another and have low values of genetic divergence. However,
      the skeleton, particularly the cranium, is interspecifically variable with
      respect to the different levels of development of some elements. Heterochrony is
      considered to have played a prominent role in generating phenotypic variation,
      especially among closely related species. Herein, the developmental origins of
      the adult cranial configuration of two species of Telmatobius are explored. The
      interactions among larval and postmetamorphic growth, sexual maturation, and
      ossification sequence in T. oxycephalus and T. rubigo are studied. Although there
      are no substantial changes in the sequences of ossification of the cranium, it is
      likely that differential timing of larval periods is related to adult cranial
      characters. The prolonged larval development of T. rubigo may result in
      peramorphic configurations of bones that ossify during pre-metamorphosis. This
      long developmental time would also explain why the gonads of T. rubigo are highly
      differentiated by the end of metamorphosis. In this species, sexual maturation
      may be attained precociously in relation to metamorphosis, thereby reducing
      postmetamorphic developmental time of late-onset bones, which have paedomorphic
      configurations (e.g., vomer, neopalatine, and columella). An inverse pattern
      characterizes T. oxycephalus, suggesting that the duration of larval life is
      related to skeletal configuration in Telmatobius.

PMID- 30117611
TI  - The functional anatomy of external genitalia in the black tiger prawn (Penaeus
      monodon) studied by micro-computed tomography and scanning electron microscopy.
AB  - Although artificial insemination has been used for decades in Penaeus monodon
      aquaculture, the interaction of male and female external genitalia during
      spermatophore transfer has not been fully documented. As a result, studying the
      functional anatomy of this process may help to better refine the insemination
      technique. The sexual act in penaeoid prawns is virtually impossible to observe
      directly; as a result, this study aimed to describe the functional anatomy and
      interaction of external genitalia, such as the petasma, appendices masculinae and
      genital papillae of the male, with that of the thelycum and genital lobes of the
      female, using a combination of micro-computed tomography and scanning electron
      microscopy. We hypothesise that the spermatophores are ejaculated into the
      ventromedial groove of the petasma and squeezed by abdominal flexure into the
      spermathecae of female's thelycum. During this process, the 'spike-like' setae
      observed on the petasma and appendices masculinae are speculated to control the
      transferring direction of the spermatophores. The approach of three dimensional
      remodelling and animation reported in this study may prove useful in the
      examination of further hypotheses related to the functional anatomy of external
      genitalia and/or appendages for other crustacean species.

PMID- 30117612
TI  - The vertebrate middle and inner ear: A short overview.
AB  - The evolution of the various hearing adaptations is connected to major structural
      changes in nearly all groups of vertebrates. Besides hearing, the detection of
      acceleration and orientation in space are key functions of this mechanosensory
      system. The symposium "show me your ear - the inner and middle ear in
      vertebrates" held at the 11th International Congress of Vertebrate Morphology
      (ICVM) 2016 in Washington, DC (USA) intended to present current research
      addressing adaptation and evolution of the vertebrate otic region, auditory
      ossicles, vestibular system, and hearing physiology. The symposium aimed at an
      audience with interest in hearing research focusing on morphological, functional,
      and comparative studies. The presented talks and posters lead to the
      contributions of this virtual issue highlighting recent advances in the
      vertebrate balance and hearing system. This article serves as an introduction to
      the virtual issue contributions and intends to give a short overview of research
      papers focusing on vertebrate labyrinth and middle ear related structures in past
      and recent years.

PMID- 30117613
TI  - The larval ontogeny of Coryphaeschna perrensi (McLachlan, 1887): Supporting
      monophyletic groups in Aeshnidae dragonflies (Insecta: Odonata: Anisoptera).
AB  - The development of the larval external morphology of Coryphaeschna perrensi is
      reported based primarily on a comparison of successive exuviae of reared
      specimens, with the second stadium larvae first described separately. Accentuated
      changes observable throughout successive moltings occur in some structures, such
      as the head capsule, labium, and anal appendages, allowing for the definition of
      characters with naturally ordered, polarized, and linear states (transformation
      series) by ontogenetic evidence. The terminal (less general) and nonterminal
      (more general) states of the described transformation series correspond by
      primary homology to the conditions found in larvae of other dragonfly species.
      Consequently, as the result of a parsimony analysis and subsequently ontogenetic
      rooting, the disposition of the states of 17 characters in a sample of final
      stadium larvae of 23 species, representatives of the six Aeshnidae tribes (21)
      and Austropetaliidae (2), results in a hierarchical network comprising six
      distinct taxonomic levels of inclusion of C. perrensi. The levels correspond to
      Aeshnidae, Aeshninae, Aeshnini (part) + Gynacanthini, Coryphaeschna + Remartinia,
      Coryphaeschna, and Coryphaeschna except C. adnexa, which are groups previously
      recognized as monophyletic resulting from analyses considering adult morphology.
      Immature insect morphology coupled with ontogenetic observation presenting great
      potential to hypothesize phylogenetic relationships and investigate heterochronic
      events.

PMID- 30117614
TI  - III-Nitride Polymorphs: XN (X=Al, Ga, In) in the Pnma Phase.
AB  - The structural, mechanical, elastic anisotropy, and electronic properties,
      together with the stability, effective mass of holes and electrons for XN (X=Al,
      Ga, In) in the Pnma phase are investigated by using density functional theory
      calculations. The elastic constants and the phonon spectra all manifest III
      nitride polymorphs: XN (X=Al, Ga, In) in the Pnma phase in this work are
      mechanically and dynamically stable at ambient pressure. Al atoms, Ga atoms, and
      In atoms lead to new electrical and band-gap properties: XN (X=Al, Ga, In) in the
      Pnma phase are all semiconductor materials with direct band gaps of 4.76 eV, 2.80
      eV, and 0.66 eV, respectively, which present great application potentials in the
      new generation electronic devices such as ultraviolet detectors, visible light
      detectors, infrared detectors, violet-light diodes, and light-emitting diodes.

PMID- 30117615
TI  - In vivo diffusion MRI detects early spinal cord axonal pathology in a mouse model
      of amyotrophic lateral sclerosis.
AB  - Diffusion magnetic resonance imaging (MRI) exhibits contrast that identifies
      macro- and microstructural changes in neurodegenerative diseases. Previous
      studies have shown that MR diffusion tensor imaging (DTI) can observe changes in
      spinal cord white matter in animals and humans affected with symptomatic
      amyotrophic lateral sclerosis (ALS). The goal of this preclinical work was to
      investigate the sensitivity of DTI for the detection of signs of tissue damage
      before symptoms appear. High-field MRI data were acquired using a 9.4-T animal
      scanner to examine the spinal cord of an ALS mouse model at pre- and post
      symptomatic stages (days 80 and 120, respectively). The MRI results were
      validated using yellow fluorescent protein (YFP) via optical microscopy of spinal
      cord tissue slices collected from the YFP,G93A-SOD1 mouse strain. DTI maps of
      diffusion-weighted imaging (DWI) signal intensity, mean diffusivity (MD),
      fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD)
      were computed for axial slices of the lumbar region of the spinal cord.
      Significant changes were observed in FA (6.7% decrease, p < 0.01), AD (19.5%
      decrease, p < 0.01) and RD (16.1% increase, p < 0.001) at postnatal day 80 (P80).
      These differences were correlated with changes in axonal fluorescence intensity
      and membrane cellular markers. This study demonstrates the value of DTI as a
      potential tool to detect the underlying pathological progression associated with
      ALS, and may accelerate the discovery of therapeutic strategies for patients with
      this disease.

PMID- 30117616
TI  - Skin stiffness in ray-finned fishes: Contrasting material properties between
      species and body regions.
AB  - The skin of aquatic vertebrates surrounds all the mechanical lineages of the body
      and must, therefore, play an important role in locomotion. A cross-woven
      collagenous dermal design has converged across several clades of vertebrates.
      Despite this intriguing pattern, the biomechanical role of skin in swimming
      fishes remains largely unknown. A direct force transmission role for fish skin
      has been proposed, a hypothesis that is supported by the arrangement of the
      connective tissues linking the skin to the axial musculature. To evaluate this
      direct force-transmission hypothesis, we undertook hundreds of uniaxial tensile
      tests on skin samples from coho salmon (Oncorhynchus kisutch), Florida pompano
      (Trachinotus carolinus), and red snapper (Lutjanus campechanus). To do this, we
      developed highly precise, low-cost, custom-built material testing units. To
      augment our data, we also assembled a data set of skin stiffness of four
      additional species of actinopterygians fishes from previously published studies.
      We found that stiffness varies significantly between species and that the skin of
      our study species was increasingly stiff along a rostrocaudal gradient. Placing
      our results in the context of the limited body of previous work, we found that
      species with lower skin stiffness exhibit shorter propulsive wavelengths and low
      thrust production at the caudal fin and species with higher skin stiffness
      possess longer propulsive wavelengths and high thrust production at the caudal
      fin. In addition, we found that mean collagen fiber angle was close to 50 degrees
      and that fiber angle was lower in posterior samples than in anterior and
      midlateral samples. Taken as a whole, our mechanical and morphological results
      support the hypothesis that the skin functions as an important direct force
      transmission device in actinopterygians whereby muscular force generated in
      anterior myotomes is transmitted to the posterior of the body through the
      increasingly stiff skin.

PMID- 30117618
TI  - Nocardia seriolae infection in the cultured eel Anguilla japonica in Korea.
AB  - Mass mortality occurred at an Anguilla japonica eel farm equipped with a
      recirculating aquaculture system in Gimcheon, Korea, from late spring to early
      summer 2015. The cumulative 3-month mortality was 16% (approximately 24,300
      150,000 fish). The majority of affected fish displayed ulcerative lesions that
      progressed to petechial haemorrhages and small white granulomas in the major
      organs. A Gram-positive, acid-fast, nonmotile bacterium was isolated from
      internal organ lesions. Phylogenetic analysis of 16S rRNA identified the species
      as Nocardia seriolae and the strain was designated EM150506. Afterwards, naive
      eels were injected with 1.8 * 107 colony-forming units per fish to confirm the
      strain's pathogenicity, which resulted in a 20% mortality rate within 4 weeks.
      However, surviving fish still exhibited white N. seriolae colonies in internal
      organs. To our knowledge, this is the first report of a N. seriolae infection in
      cultured eel.

PMID- 30117619
TI  - Xeroderma pigmentosum group D: Report of a novel combination of ERCC2 variations
      and its phenotype.

PMID- 30117617
TI  - Development of a diagnostic system for detection of specific antibodies and
      antigens against Middle East respiratory syndrome coronavirus.
AB  - Middle East respiratory syndrome coronavirus (MERS-CoV) is a single-stranded RNA
      virus that causes severe respiratory disease in humans with a high fatality rate.
      Binding of the receptor binding domain (RBD) of the spike (S) glycoprotein to
      dipeptidyl peptidase 4 is the critical step in MERS-CoV infection of a host cell.
      No vaccines or clinically applicable treatments are currently available for MERS
      CoV. Therefore, rapid diagnosis is important for improving patient outcomes
      through prompt treatment and protection against viral outbreaks. In this study,
      the aim was to establish two ELISA systems for detecting antigens and antibodies
      against MERS-CoV. Using a recombinant full-length S protein, an indirect ELISA
      was developed and found to detect MERS-CoV-specific antibodies in animal sera and
      sera of patient with MERS. Moreover, MAbs were induced with the recombinant S
      protein and RBD and used for sandwich ELISA to detect the MERS-CoV S protein.
      Neither ELISA system exhibited significant intra-assay or inter-assay variation,
      indicating good reproducibility. Moreover, the inter-day precision and
      sensitivity were adequate for use as a diagnostic kit. Thus, these ELISAs can be
      used clinically to diagnose MERS-CoV.

PMID- 30117620
TI  - alpha-Sila-Dipeptides: Synthesis and Characterization.
AB  - The first two alpha-sila-dipeptides, 7 and cyclo-sila-dipeptide 8, were
      synthesized and characterized by several methods, including X-ray
      crystallography. Bulky t-BuMe2 Si substituents provide some kinetic stabilization
      to the synthesized molecules. 7 and 8 are the first examples of a "Si for C
      switch" in the central alpha-position of an amino acid or a peptide, in which
      silicon is bonded to both the amino and the carbonyl groups.

PMID- 30117622
TI  - Robust Manipulation of Magnetism in Dilute Magnetic Semiconductor (Ga,Mn)As by
      Organic Molecules.

PMID- 30117621
TI  - Change of lecithotrophic to matrotrophic nutrition during gestation in the
      viviparous teleost Xenotoca eiseni (Goodeidae).
AB  - Teleosts possess unique features of the female reproductive system compared with
      the rest of vertebrates, features that define the characteristics of their
      viviparity. Viviparity involves new maternal-embryonic relationships detailing
      the most diverse structures during gestation that include embryonic nutrition. In
      order to analyze the morphological features of the complex nutrition in
      viviparous teleosts during intraovarian gestation, this study utilizes the
      goodeid Xenotoca eiseni as a model. Ovarian gestation in X. eiseni, as in all
      goodeids, is intraluminal; the early embryo moves from the follicle to the
      ovarian lumen where gestation continues. The scarce yolk in the oocytes implies
      that the initial lecithotrophy is replaced by matrotrophy, with nutrients
      provided via maternal tissues. The nutrients are absorbed by the embryo mainly by
      trophotaenia, extensions of the embryonic intestine into the ovarian lumen. This
      histological study analyses the structures involved in these two types of
      nutrition and when they occur during gestation in X. eiseni. The morphology
      displayed in this study demonstrated the extended simultaneity of lecithotrophy
      and matrotrophy during gestation with the progressive reduction of lecithotrophy
      and increase of matrotrophy. Similarly, it describes the development of complex
      embryonic structures for metabolic exchange with the maternal tissues associated
      with matrotrophy; specifically the branchial placenta and mainly the
      trophotaenia.

PMID- 30117623
TI  - Mixed Ionic and Electronic Conductor for Li-Metal Anode Protection.

PMID- 30117624
TI  - Selective Decrease in Allodynia With High-Frequency Neuromodulation via High
      Electrode-Count Intrafascicular Peripheral Nerve Interface After Brachial Plexus
      Injury.
AB  - OBJECTIVES: Kilohertz high-frequency alternating current (KHFAC) electrical nerve
      stimulation produces a reversible nerve block in peripheral nerves in human
      patients with chronic pain pathologies. Although this stimulation methodology has
      been verified with nonselective extrafascicular electrodes, the effectiveness of
      producing a selective nerve block with more-selective intrafascicular electrodes
      has not been well documented. The objective of this study was to examine whether
      intrafascicular electrodes can block painful stimuli while preserving conduction
      of other neural activity within the implanted nerve. MATERIALS AND METHODS: We
      analyzed the effects of various stimulation waveforms delivered through Utah
      Slanted Electrode Arrays (USEAs) implanted in the median nerve of a male human
      subject with a left brachial plexus injury. We compared KHFAC stimulation with a
      sham control. RESULTS: KHFAC stimulation through USEA electrodes produced a
      reduction in pain sensitivity in the palmar aspect of the left middle finger.
      KHFAC had limited effects on the patient's ability to feel tactile probing in the
      same area or move the digits of his left hand. Other tested stimulation
      parameters either increased or showed no reduction in pain. CONCLUSIONS: KHFAC
      stimulation in peripheral nerves through intrafascicular electrodes demonstrated
      a selective reduction in pain sensitivity while preserving other nerve functions.
      This treatment may benefit patient populations who have chronic pain originating
      from peripheral nerves, but who do not want to block whole-nerve function in
      order to preserve sensory and motor function reliant on the implanted nerve.
      Furthermore, KHFAC may benefit patients who respond negatively to other forms of
      peripheral nerve stimulation therapy.

PMID- 30117625
TI  - Nomogram predicting survival of hepatocellular carcinoma with portal vein tumour
      thrombus after curative resection.
AB  - BACKGROUND: The aim of this study was to combine clinicopathologic variables
      associated with overall survival and disease-free survival after curative
      resection for hepatocellular carcinoma (HCC) with portal vein tumour thrombus
      (PVTT) into a prediction nomogram. METHODS: We retrospectively analysed 358
      patients who underwent curative resection for HCC with PVTT at the Eastern
      Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai,
      China. Two-thirds of the patients were randomly assigned to the training set (n =
      252) and one-third were assigned to the validation set (n = 106). Multivariate
      analysis by Cox proportional hazards regression was performed using the training
      set, and the nomogram was constructed. Discrimination and calibration were
      performed using the validation set. RESULTS: The multivariate Cox model
      identified alpha fetoprotein, hepatitis B surface antigen (HBsAg), tumour
      diameter, tumour capsule, PVTT type and TNM stage as covariates associated with 1
      year survival, and alpha fetoprotein, HBsAg, tumour diameter, tumour capsule and
      PVTT type with half-year disease-free survival. In the validation set, the
      nomogram exhibited superior discrimination power (Harrell's C-index 0.78)
      compared with the American Joint Committe on Cancer TNM classification, the
      Cancer of the Liver Italian Program grade and the Japan Integrated Staging grade.
      Calibration of the nomogram-predicted survival corresponding closely with the
      actual survival, the predicted survival was within a 10% margin of ideal
      nomogram. CONCLUSION: We developed a nomogram predicting 1-year overall survival
      and half-year disease-free survival after curative resection for HCC with PVTT.
      Validation data sets revealed good discrimination and calibration, suggesting
      good clinical utility. The nomogram improved individualized predictions of
      survival.

PMID- 30117626
TI  - Early outcomes of two-stage minimally invasive oesophagectomy in an Australian
      institution.
AB  - BACKGROUND: Minimally invasive oesophagectomy (MIO) has a steep learning curve.
      We report our outcomes of a standardized 25 mm circular-stapled anastomosis using
      a trans-orally placed anvil (OrvilTM). The objective of this study is to report
      the initial experience of introducing two-stage MIO to an Australian tertiary
      health service. METHODS: We describe our consecutive case series of all MIOs
      performed from a prospectively maintained database. We assessed the morbidity and
      mortality of MIO at our institution. We compared our first 30 cases to the second
      cohort of 32 cases. RESULTS: There were 62 two-stage MIOs performed from 2011 to
      2015. The average age was 65 years. Median length of stay was 13 days (5-72
      days). Median number of total lymph nodes was 14. Conversion occurred in three
      patients (5%). Major morbidity was 45%. Delayed gastric emptying 6% (n = 4),
      pneumonia 6% (n = 4), chyle leak 6% (n = 4), pulmonary embolus 2% (n = 1) and
      grade II or III anastomotic leak 5% (n = 4). One conduit ischaemia (2%) required
      reoperation and formation of oesophagostomy. There was one post-operative death
      within 30 days. There were five post-oesophagectomy hiatal hernias requiring re
      operation (8%). There was a significant improvement in operative time (minutes)
      from the first to second cohort 588 versus 464 (P-value 0.01). CONCLUSION: The
      introduction of two-stage MIO to the Australian setting can be safely instituted.
      Our unit was still within a learning curve after 30 cases.

PMID- 30117627
TI  - Sculpting the skull through neurosensory epithelial-mesenchymal signaling.
AB  - The vertebrate skull is a complex structure housing the brain and specialized
      sensory organs, including the eye, the inner ear, and the olfactory system. The
      close association between bones of the skull and the sensory organs they encase
      has posed interesting developmental questions about how the tissues scale with
      one another. Mechanisms that regulate morphogenesis of the skull are hypothesized
      to originate in part from the encased neurosensory organs. Conversely, the
      developing skull is hypothesized to regulate the growth of neurosensory organs,
      through mechanical forces or molecular signaling. Here, we review studies of
      epithelial-mesenchymal interactions during inner ear and olfactory system
      development that may coordinate the growth of the two sensory organs with their
      surrounding bone. We highlight recent progress in the field and provide evidence
      that mechanical forces arising from bone growth may affect olfactory epithelium
      development. Developmental Dynamics 2018. (c) 2018 Wiley Periodicals, Inc.

PMID- 30117628
TI  - Improvement of anaphylactoid purpura in a patient with ascending colon cancer
      after colectomy.

PMID- 30117629
TI  - Influence of liver fibrosis on prognosis after surgical resection for resectable
      single hepatocellular carcinoma.
AB  - BACKGROUND: Surgical resection (SR) is recommended for single hepatocellular
      carcinoma (HCC) in patients with well-preserved liver function. However,
      unexpected liver fibrosis sometimes found at the SR which leads to a poor
      outcome. This study investigated the influence of liver fibrosis on prognosis
      after SR for HCC. METHODS: A total of 189 patients with Child-Turcotte-Pugh grade
      A who underwent curative SR for a single HCC <5 cm were evaluated. Patients were
      assigned to two groups based on the degree of fibrosis (mild or severe), as
      determined by histological evaluation. RESULTS: Severe fibrosis was present in 49
      patients (25.9%); these patients had greater posthepatectomy liver failure (P =
      0.000) and HCC recurrence (P = 0.016). Severe liver fibrosis (hazard ratio (HR) =
      1.849, 95% confidence interval (CI) 1.191-2.869; P = 0.006), microvascular
      invasion (HR = 1.854, 95% CI 1.183-2.906; P = 0.007), and poor histologic grade
      (HR = 2.097, 95% CI 1.230-3.574; P = 0.007) were related to HCC recurrence.
      CONCLUSION: Severe fibrosis can be found even in patients with well-preserved
      liver function and it leads to poorer early post-operative and late oncologic
      outcomes, therefore it should be considered before therapeutic decision making of
      HCC.

PMID- 30117630
TI  - Sacral Burst Neuromodulation via Caudal Approach as a Treatment for Chronic
      Coccydynia.

PMID- 30117631
TI  - Adolescent Psychological Functioning and Membership in Latent Adolescent-Parent
      Communication Dual Trajectory Classes.
AB  - The primary goal of this study was to examine the relationship between
      adolescents' psychological functioning (as indicated by depressive symptoms) and
      substance use (alcohol and drug use) and membership in adolescent-parent
      communication trajectory subgroups in a large, diverse community sample of
      adolescents from the United States (n = 1,057; 53% female; 51% Caucasian; Age: M
      = 16.15, SD = .75). Adolescents completed questionnaires at three annual
      assessments. Fit indices from parallel process growth mixture models suggested
      three dual trajectory classes: (1) Average communication with both parents
      (Average-Both); (2) Good adolescent-mother and poor adolescent-father
      communication (Good-Mom/Poor-Dad); and (3) Poor adolescent-mother and good
      adolescent-father communication (Poor-Mom/Good-Dad). The trajectory classes
      differed by gender. In addition, psychological functioning and substance use were
      differentially related to the trajectory classes.

PMID- 30117632
TI  - Efficacy and safety of low-dose prophylaxis of highly purified plasma-derived
      factor VIII concentrate produced by the National Blood Centre, Thai Red Cross
      Society.

PMID- 30117633
TI  - Compartmentalized devices as tools for investigation of human brain network
      dynamics.
AB  - Neuropsychiatric disorders have traditionally been difficult to study due to the
      complexity of the human brain and limited availability of human tissue. Induced
      pluripotent stem (iPS) cells provide a promising avenue to further our
      understanding of human disease mechanisms, but traditional 2D cell cultures can
      only provide a limited view of the neural circuits. To better model complex brain
      neurocircuitry, compartmentalized culturing systems and 3D organoids have been
      developed. Early compartmentalized devices demonstrated how neuronal cell bodies
      can be isolated both physically and chemically from neurites. Soft lithographic
      approaches have advanced this approach and offer the tools to construct novel
      model platforms, enabling circuit-level studies of disease, which can accelerate
      mechanistic studies and drug candidate screening. In this review, we describe
      some of the common technologies used to develop such systems and discuss how
      these lithographic techniques have been utilized to advance our understanding of
      neuropsychiatric disease. Finally, we address other in vitro model platforms such
      as 3D culture systems and organoids and compare these models with
      compartmentalized models and ask important questions regarding how we can further
      harness induced pluripotent stem cells in these engineered culture systems for
      the development of improved in vitro models. This article is protected by
      copyright. All rights reserved.

PMID- 30117634
TI  - General Surgery Prioritization Tool: a pilot study.
AB  - BACKGROUND: The prioritization of elective surgical wait-lists remains a
      contentious issue. Multiple new tools and systems have been developed to attempt
      to reliably prioritize patients. This study pilots one such system, the General
      Surgery Prioritization Tool and compares it to the existing triage system of
      clinical judgement. The aim was to determine if the new tool reflects clinical
      judgement. Secondary aims were to assess for any bias in its application to
      different patient groups or its application by different scorers. METHOD: A
      cohort of 392 patients was identified who were wait-listed for non-cancer
      elective surgery between July 2015 and February 2016. The General Surgery
      Prioritization Tool was applied after traditional prioritization using clinical
      judgement. The scores produced by the new tool were compared to the clinical
      judgement categories. Differences in scores based on gender, ethnicity, age,
      surgical condition and surgeon were then analysed. RESULTS: There was
      statistically significant correlation in the new tool scores with traditional
      triage groups (P < 0.0001). There were no statistically significant differences
      in mean scores attributable to gender, age or ethnicity. There were minimal
      differences in mean scores between common surgical conditions. Except for one
      outlier the mean scores were consistent across 17 surgeons. CONCLUSION: This
      pilot study has found the General Surgery Prioritization Tool to reflect clinical
      judgement and to be generalizable by age, gender, ethnicity and prioritizing
      surgeon. The tool is at least as clinically reliable as traditional methods in
      the triage for elective general surgery with the advantage of being a more
      explicit process.

PMID- 30117635
TI  - Spinal Cord Stimulation Infection Rate and Risk Factors: Results From a United
      States Payer Database.
AB  - OBJECTIVE: Surgical site infections can cause negative clinical and economic
      outcomes. A recent international survey on Spinal Cord Stimulation (SCS)
      infection control practices demonstrated low compliance with evidence-based
      guidelines. This study defines infection rate for SCS implants and identifies
      infection risk factors. MATERIALS AND METHODS: A retrospective analysis of the
      MarketScan(r) Databases identified patients with SCS implant (2009-2014) and
      continuous health plan enrollment for >=12-months (12 m) preimplant. For logistic
      regression analysis, patients were enrolled for 12 m postimplant. Kaplan-Meier
      and Cox Proportional Hazard survival analyses assessed time to infection, with
      infection rate reported at 12 m postimplant. Logistic regression characterized
      risk factors based on demographics, comorbidities, and clinical characteristics.
      RESULTS: In the logistic regression (n = 6615), 12 m device-related infection
      rate was 3.11%. Infection risk factors included peripheral vascular disease (OR,
      1.784; 95% CI: 1.011-3.149; p = 0.0457) and infection in 12 m before implant (OR,
      1.518; 95% CI: 1.022-2.254; p = 0.0386). The odds of patients experiencing an
      infection decreased by 3.2% with each additional year of age (OR, 0.968; 95% CI:
      0.952-0.984; p < 0.0001). Survival analysis (n = 13,214) identified prior
      infection (HR, 1.770; 95% CI: 1.342-2.336; p < 0.0001) as a risk factor.
      Infection was less likely in older patients (HR, 0.974; 95% CI: 0.962-0.986; p <
      0.0001). Expected risk factors including obesity, diabetes, and smoking were not
      identified as risk factors in this analysis. There was no significant difference
      between infection rate for initial and replacement implants. CONCLUSIONS: The
      3.11% SCS-related infection rate within 12 m of implant emphasizes the need for
      improved infection control practices. Research is needed to limit SCS infections
      in younger patients and those with infection history.

PMID- 30117636
TI  - Fragmented QRS as a predictor of in-hospital life-threatening arrhythmic
      complications in ST-elevation myocardial infarction patients.
AB  - BACKGROUND: Fragmented QRS (fQRS) complex is an electrocardiographic pattern that
      reflects the inhomogeneity of ventricular depolarization. The aims of this study
      were to determine the prognostic significance of fQRS for predicting in-hospital
      life-threatening arrhythmic complications in ST-elevation myocardial infarction
      (STEMI) patients, and to identify the most appropriate duration of cardiac rhythm
      monitoring in STEMI patients with fQRS. METHODS: Patients diagnosed with and
      treated for STEMI at Siriraj Hospital (Bangkok, Thailand) during 2009-2012 were
      enrolled. Patients were divided according to fQRS status (having or not having
      fQRS) at hospital admission. The primary outcome was in-hospital life-threatening
      arrhythmic events, including sustained ventricular tachycardia and ventricular
      fibrillation. Time to last life-threatening arrhythmic event from hospital
      admission was recorded. RESULTS: Of the 452 patients that were included, 96
      patients (21.2%) had fQRS. There were significantly more life-threatening
      arrhythmic events in the fQRS group than in the non-fQRS group (22.9% vs. 4.5%,
      respectively; p < 0.001). Median (IQR) time to last life-threatening arrhythmic
      event from hospital admission was significantly longer in fQRS than in non-fQRS
      (6.58 hr [3.08-39.34] vs. 2.59 hr [1.75-5.75], respectively; p = 0.047).
      Multivariate analysis identified fQRS as an independent predictor of in-hospital
      life-threatening arrhythmic events (OR: 4.162, 95% CI: 1.669-10.384; p = 0.002).
      CONCLUSIONS: The presence of fQRS complex on admission ECG was found to be an
      independent predictor of in-hospital life-threatening arrhythmic events in STEMI
      patients. Since the time to last life-threatening arrhythmic event from admission
      was longer in fQRS than in non-fQRS, cardiac rhythm monitoring longer than 24-48
      hr may be needed in patients with fQRS.

PMID- 30117637
TI  - RheoScale: A tool to aggregate and quantify experimentally determined
      substitution outcomes for multiple variants at individual protein positions.
AB  - Human mutations often cause amino acid changes (variants) that can alter protein
      function or stability. Some variants fall at protein positions that
      experimentally exhibit "rheostatic" mutation outcomes (different amino acid
      substitutions lead to a range of functional outcomes). In ongoing studies of
      rheostat positions, we encountered the need to aggregate experimental results
      from multiple variants, to describe the overall roles of individual positions.
      Here, we present "RheoScale" which generates quantitative scores to discriminate
      rheostat positions from those with "toggle" (most substitutions abolish function)
      or "neutral" (most substitutions have wild-type function) outcomes. RheoScale
      scores facilitate correlations of experimental data (such as binding affinity or
      stability) with structural and bioinformatic analyses. The RheoScale calculator
      is encoded into a Microsoft Excel workbook and an R script. Example analyses are
      shown for three model protein systems, including one assessed via deep mutational
      scanning. The RheoScale calculator quickly and efficiently provided quantitative
      descriptions that were in good agreement with prior qualitative observations. As
      an example application, scores were compared to the example proteins' structures;
      strong rheostat positions tended to occur in dynamic locations. In the future,
      RheoScale scores can be easily integrated into computational studies to
      facilitate improved algorithms for predicting outcomes of human variants.

PMID- 30117638
TI  - Chemical effects of chewing sticks made of Salvadora persica.
AB  - OBJECTIVE: The chewing sticks are widely used in many regions of Asia and Africa
      as a traditional tool to maintain oral hygiene. Salvadora persica L. (S.
      persica), also known as Arak or Miswak, a member of the salvadoraceae family.
      Chewing sticks, made up from S. persica, have chemical antibacterial properties
      and mechanical effects. The study aimed to investigate possible chemical effects
      of S. persica on dental plaque, sub-gingival microbiota and gingival
      inflammation. In order to achieve this, we inactivated some sticks through
      boiling to be used as inactive, but mechanically comparable control sticks.
      METHODS: In a double-blinded crossover trial, 24 patients with mild-to-moderate
      periodontitis were randomly allocated to use either fresh activated Miswak or
      inactivated Miswak for 3-week period. Plaque index (PI), gingival index (GI),
      visual plaque index (VPI) and bleeding on probing (BOP) were evaluated before and
      immediately following the experimental period. Sub-gingival plaque samples were
      analysed using DNA-DNA hybridization technique. The study was repeated with the
      participants switching the type of Miswak they used after a 7-week of "washout"
      period. RESULTS: There were no significant differences in the microflora after
      using active and inactive Miswak. Sixteen species of bacteria showed an increase
      (P < 0.05) after the usage of inactive Miswak, as compared to pretreatment
      values. No species showed a similar change after the use of active Miswak. There
      were no significant differences between active and inactive Miswak regarding the
      registered clinical variables. CONCLUSION: This study has not shown any clinical
      effect of the chemically active Miswak, but there was a tendency towards an
      effect on the microflora.

PMID- 30117639
TI  - Frequency of crown and root dilaceration of permanent incisors after dental
      trauma to their predecessor teeth.
AB  - BACKGROUND/AIMS: Dental trauma to the predecessor teeth can cause crown and root
      dilacerations to the successor teeth, which can interfere with the normal
      development of permanent teeth. The aims of this study were to verify the types
      of trauma more frequent to the predecessor teeth that cause dilaceration to their
      successor teeth, to determine the frequency of crown and root dilacerations in
      permanent incisors, taking into account the child's age at the time of trauma,
      and to describe the types of treatment performed. MATERIALS AND METHODS: Details
      of 815 anterior primary teeth with dental injury were obtained from 483 dental
      records of children aged 0-9 years at the time of trauma. RESULTS: Of 815
      traumatized primary teeth, 161 successor teeth were clinically and
      radiographically reviewed until complete eruption and had some type of sequel.
      Avulsion and intrusive luxation were the most frequent types of trauma to the
      predecessor teeth that caused dilaceration to their successor teeth. Enamel
      discoloration (30.4%), hypoplasia (23.6%), root (14.3%) and crown (9.9%)
      dilacerations were the most common sequelae observed in the successor teeth. Root
      and crown dilacerations were more frequent in children aged more than and up to 3
      years, respectively. Tooth extraction and orthodontic treatment were the most
      common treatments. CONCLUSIONS: Dentists must be aware of the relationship
      between the child's age at the time of trauma to the predecessor tooth and the
      type of sequel to the successor tooth in order to diagnose, monitor, and treat
      the sequel properly.

PMID- 30117640
TI  - Factors associated with effective coverage of child health services in Burkina
      Faso.
AB  - OBJECTIVE: To identify factors associated with both crude and effective health
      service coverage of under-fives in rural Burkina Faso. METHODS: In a cross
      sectional study, 494 first-line health facilities, 7347 households and 12 497
      under-fives were surveyed. Two sequential logistic random effects models were
      conducted to assess factors associated with crude and effective coverage.
      RESULTS: Of 614 children under-five with a reported illness episode, 427 (69.5%)
      received care at a health facility. Of those, 274 (64.1%) received care at a
      health facility providing at least the minimum threshold of service quality. We
      found that younger age, having a severe illness, shorter distance between
      household and health facility, and being from wealthier households were
      positively associated with crude coverage. In addition, low patient caseload and
      longer consultation had a positive association, while frequent facility
      supervisions had a negative association with effective coverage. Moreover, the
      nurse to clinical staff ratio at the health facility was positively associated
      with both crude and effective coverage. CONCLUSION: Our study found that crude
      coverage is associated with pre-disposing and enabling factors of health care
      access, while the availability of nurses is a strong predictor for both crude and
      effective coverage. This suggests that in the context of scarcity of resources,
      investing in human resources in health sector could be one of the priorities for
      decision-makers to ensure children in need not only access to healthcare but also
      good quality of care.

PMID- 30117641
TI  - Investigating a novel split-filter dual-energy CT technique for improving
      pancreas tumor visibility for radiation therapy.
AB  - PURPOSE: Tumor delineation using conventional CT images can be a challenge for
      pancreatic adenocarcinoma where contrast between the tumor and surrounding
      healthy tissue is low. This work investigates the ability of a split-filter dual
      energy CT (DECT) system to improve pancreatic tumor contrast and contrast-to
      noise ratio (CNR) for radiation therapy treatment planning. MATERIALS AND
      METHODS: Multiphasic scans of 20 pancreatic tumors were acquired using a split
      filter DECT technique with iodinated contrast medium, OMNIPAQUETM . Analysis was
      performed on the pancreatic and portal venous phases for several types of DECT
      images. Pancreatic gross target volume (GTV) contrast and CNR were calculated and
      analyzed from mixed 120 kVp-equivalent images and virtual monoenergetic images
      (VMI) at 57 and 40 keV. The role of iterative reconstruction on DECT images was
      also investigated. Paired t-tests were used to assess the difference in GTV
      contrast and CNR among the different images. RESULTS: The VMIs at 40 keV had a
      110% greater image noise compared to the mixed 120 kVp-equivalent images (P <
      0.0001). VMIs at 40 keV increased GTV contrast from 15.9 +/- 19.9 HU to 93.7 +/-
      49.6 HU and CNR from 1.37 +/- 2.05 to 3.86 +/- 2.78 in comparison to the mixed
      120 kVp-equivalent images. The iterative reconstruction algorithm investigated
      decreased noise in the VMIs by about 20% and improved CNR by about 30%.
      CONCLUSIONS: Pancreatic tumor contrast and CNR were significantly improved using
      VMIs reconstructed from the split-filter DECT technique, and the use of iterative
      reconstruction further improved CNR. This gain in tumor contrast may lead to more
      accurate tumor delineation for radiation therapy treatment planning.

PMID- 30117642
TI  - Transcription factor ATF3 mediates the radioresistance of breast cancer.
AB  - This study was designed to research the influence of activating transcription
      factor 3 (ATF3) on the radioresistance of breast cancer. ATF3 expression was
      measured by qRT-PCR and immunohistochemistry. Cancerous cell lines were cultured
      in vitro, and the expression of ATF3 was gauged by both qRT-PCR and Western blot
      before and after the radiation therapy. Cellular cycle and apoptosis were
      analysed by flow cytometry. Changes in the expression of corresponding proteins
      in the downstream pathways were identified by Western blot. Tumour xenograft was
      used to evaluate the effect of ATF3 in vivo. ATF3 was observed stronger in breast
      cancer tissues and cells. After radiation therapy, the expression of ATF3 in
      breast cancer cells was up-regulated. Silencing ATF3 could promote G2/M phase
      block, facilitate cell apoptosis and decrease clonogenic survival rate. The
      overexpression of ATF3 could curb G2/M-phase block, cell apoptosis and increase
      clonogenic survival rate. Overexpression ATF3 could increase radioresistance by
      up-regulating the level of phosphorylation of Akt in the PI3K/Akt signalling
      pathway. Radioresistance of breast cancer cells could be alleviated by inhibiting
      the PI3K/Akt signalling pathway. ATF3 could also promote radioresistance in vivo.
      ATF3 gene was able to promote radioresistance of breast cancer cells.

PMID- 30117643
TI  - Compatibility of Beauveria bassiana and alternative phytosanitary products.
AB  - AIMS: To assess the compatibility of alternative phytosanitary products (APPs)
      with the entomopathogenic fungus Beauveria bassiana (Bals.) Vuillemin. METHODS
      AND RESULTS: The APPs used were Baicao, Orobor(r) , Topneem, Rotenat and
      Compostonat at concentrations recommended by the manufacturers (CR), and then
      half (1/2CR) and double (2CR). To evaluate the compatibility, the following
      parameters were analysed: germination, colony forming units (CFUs), vegetative
      growth and conidia production. Compatibility was assessed using rates of toxicity
      and biological index. The association of APPs and B. bassiana was also evaluated
      for pathogenicity against larvae of third instar Anagasta kuehniella Zeller
      (Lepidoptera: Pyralidae) (1.0 * 108 conidia per ml). The germination of conidia
      of B. bassiana was reduced only by the product Orobor(r) . The CFUs were not
      affected by any products. The colony diameter was reduced when in contact with
      the products Baicao and Orobor(r) . For conidia production per colony, all
      products reduced this parameter. None of the products affected the pathogenicity
      of the fungus on A. kuehniella. CONCLUSIONS: All APPs tested are compatible with
      B. bassiana. SIGNIFICANCE AND IMPACT OF THE STUDY: The natural products tested
      and used in the field are considered compatible with B. bassiana under laboratory
      conditions, making possible new studies and the use of these in insect control.

PMID- 30117644
TI  - A Nonconjugated Zwitterionic Polymer: Cathode Interfacial Layer Comparable with
      PFN for Narrow-Bandgap Polymer Solar Cells.
AB  - A nonconjugated, alcohol-soluble zwitterionic polymer, poly(sulfobetaine
      methacrylate) (denoted by PSBMA), is employed as cathode interfacial layer (CIL)
      in polymer solar cells (PSCs) based on PTB7-Th:PC71 BM. Compared with the control
      device without CIL, PSCs with PSBMA CILs show significant enhancement on the
      resulting performance, and the highest power conversion efficiency (PCE) of 8.27%
      is achieved. Under parallel conditions, PSCs with PSBMA as CIL show comparable
      performance than those with widely used poly[(9,9-bis(30-(N,N
      dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-ioctylfluorene)] as CIL. The
      polar groups of PSBMA not only provide a solvent orthogonal solubility in the
      process of preparation of the devices but also lead to interfacial dipole to the
      electrode, which promises a better energy level alignment. In addition, PSBMA
      based devices show better abilities of hole blocking. These results indicate that
      the zwitterionic polymer PSBMA should be a promising CIL in PSC-based narrow
      bandgap polymers.

PMID- 30117645
TI  - The Future of Polymer Science.

PMID- 30117646
TI  - Synthesis of Spirocyclic Ethers by Enantioselective Copper-Catalyzed
      Carboetherification of Alkenols.
AB  - Spirocyclic ethers can be found in bioactive compounds. This copper-catalyzed
      enantioselective alkene carboetherification provides 5,5-, 5,6- and 6,6
      spirocyclic products containing fully substituted chiral carbon centers with up
      to 99 % enantiomeric excess. This reaction features the formation of two rings
      from acyclic substrates, 1,1-disubstituted alkenols functionalized with either
      arenes, alkenes, or alkynes, and clearly constitutes a powerful way to synthesize
      chiral spirocyclic ethers.

PMID- 30117647
TI  - Unique case of atypical type A thymoma with vertebral metastasis and high 18
      fluorodeoxyglucose avidity.

PMID- 30117648
TI  - Gastrointestinal prophylaxis in patients with autoimmune blistering disease
      treated with corticosteroids: an expert survey.

PMID- 30117649
TI  - Rare adrenal ganglioneuroma encasing the inferior vena cava.

PMID- 30117650
TI  - Return to Work of Patients Treated With Spinal Cord Stimulation for Chronic Pain:
      A Systematic Review and Meta-Analysis.
AB  - BACKGROUND: Chronic pain has a substantial negative impact on work-related
      outcomes, which underscores the importance of interventions to reduce the burden.
      Spinal cord stimulation (SCS) efficiently causes pain relief in specific chronic
      pain syndromes. The aim of this review was to identify and summarize evidence on
      returning to work in patients with chronic pain treated with SCS. MATERIALS AND
      METHODS: A systematic literature review was performed including studies from
      PubMed, EMBASE, SCOPUS, and Web of Science (up till October 2017). Risk of bias
      was assessed using a modified version of the Downs & Black checklist. Where
      possible, we pooled data using random effects meta-analysis. The study protocol
      was registered prior to initiation of the review process (PROSPERO
      CRD42017077803). RESULTS: Fifteen full-text articles (total articles screened:
      2835) were included. Risk of bias for these articles was scored low. Seven trials
      provided sufficient data and were judged similar enough to be pooled for meta
      analysis on binary outcomes. SCS intervention results in a higher prevalence of
      patients at work compared with before treatment (odds ratio [OR] 2.15; 95%
      confidence interval [CI], 1.44-3.21; I2  = 42%; p < 0.001). SCS treatment also
      results in high odds to return to work (OR 29.06; 95% CI, 9.73-86.75; I2  = 0%; p
      < 0.001). CONCLUSIONS: Based on available literature, SCS proved to be an
      effective approach to stimulate return to work in patients with specific chronic
      pain syndromes.

PMID- 30117651
TI  - Lithium versus Mono/Polyvalent Ion Intercalation: Hybrid Metal Ion Systems for
      Energy Storage.
AB  - The energy storage by redox intercalation reactions is, nowadays, the most
      effective rechargeable ion battery. When lithium is used as intercalating agents,
      the high energy density is achieved at an expense of non-sustainability. The
      replacement of Li+ with cheaper monovalent ions enables to make greener battery
      alternatives. The utilization of polyvalent ions instead of Li+ permits to
      multiplying the battery capacity. Contrary to Li+ , the realization of quick and
      reversible intercalation of bigger monovalent and of polyvalent ions is a
      scientific challenge due to kinetic constraints, polarizing ion effects and
      Coulomb interactions. Herein we provide a vision how to make the intercalation of
      these ions feasible. The idea is to perform dual intercalation of ions having
      different charges, radii, preferred coordination and diffusion pathway topology.
      All these features are demonstrated by the recent knowledge on selective and non
      selective intercalation properties of oxides and polyanion compounds with layered
      and tunnel structures. Based on dual intercalation properties, the fabrication of
      hybrid metal ion batteries is presented and discussed.

PMID- 30117652
TI  - Prevalence of low anterior resection syndrome at a regional Australian centre.
AB  - BACKGROUND: With decreasing indication for abdominoperineal resection and an
      increase in sphincter preserving surgery, there is a growing population of
      patients who suffer from low anterior resection syndrome (LARS). The aim of this
      study is to use the LARS score to determine the prevalence of LARS at a regional
      centre in Australia and determine the effect of short- and long-course
      neoadjuvant therapy, anastomotic technique and interval from surgery will also be
      assessed. METHODS: Patients who had undergone an anterior resection (high, low or
      ultralow) at a regional centre over an 11-year period were identified. Eligible
      patients were contacted to complete a LARS score questionnaire. Results were
      analysed to determine the rate of major LARS and possible causative roles of
      certain patient and treatment-related variables. RESULTS: A total of 64 of 76
      patients (84%) returned completed questionnaires. The prevalence of major LARS
      was 37.5%. Short-course neoadjuvant therapy appeared to be more likely to be
      associated with major LARS compared to long course (odds ratio (OR) = 2.4, 95%
      confidence interval (CI) 0.37-15.3, P = 0.35); however, this did not reach
      statistical significance. Rates of major LARS appear to decrease slowly over time
      and J-pouch colonic anastomosis appears to be slightly protective against major
      LARS (OR = 0.7, 95% CI 0.12-3.9, P = 0.70); however, neither results were
      statistically significant. CONCLUSION: The rate of major LARS at this regional
      centre is 37.5%. Larger prospective multicentre studies are required to determine
      impact of variables such as type of neoadjuvant therapy, anastomotic techniques
      and progression of LARS over time.

PMID- 30117653
TI  - An Arabidopsis E3 ligase HUB2 increases histone H2B monoubiquitination and
      enhances drought tolerance in transgenic cotton.
AB  - The HUB2 gene encoding histone H2B monoubiquitination E3 ligase is involved in
      seed dormancy, flowering timing, defence response and salt stress regulation in
      Arabidopsis thaliana. In this study, we used the cauliflower mosaic virus (CaMV)
      35S promoter to drive AtHUB2 overexpression in cotton and found that it can
      significantly improve the agricultural traits of transgenic cotton plants under
      drought stress conditions, including increasing the fruit branch number, boll
      number, and boll-setting rate and decreasing the boll abscission rate. In
      addition, survival and soluble sugar, proline and leaf relative water contents
      were increased in transgenic cotton plants after drought stress treatment. In
      contrast, RNAi knockdown of GhHUB2 genes reduced the drought resistance of
      transgenic cotton plants. AtHUB2 overexpression increased the global H2B
      monoubiquitination (H2Bub1) level through a direct interaction with GhH2B1 and up
      regulated the expression of drought-related genes in transgenic cotton plants.
      Furthermore, we found a significant increase in H3K4me3 at the DREB locus in
      transgenic cotton, although no change in H3K4me3 was identified at the global
      level. These results demonstrated that AtHUB2 overexpression changed H2Bub1 and
      H3K4me3 levels at the GhDREB chromatin locus, leading the GhDREB gene to respond
      quickly to drought stress to improve transgenic cotton drought resistance, but
      had no influence on transgenic cotton development under normal growth conditions.
      Our findings also provide a useful route for breeding drought-resistant
      transgenic plants.

PMID- 30117654
TI  - Influence of incubation conditions on the formation of model biofilms by Listeria
      monocytogenes and Salmonella Typhimurium on abiotic surfaces.
AB  - AIMS: This research aims to develop strongly adherent and mature model biofilms
      (on a 20 cm2 polystyrene surface) for two pathogenic species, i.e. Listeria
      monocytogenes and Salmonella Typhimurium. These model biofilms can be used as
      standards to study biofilms or to study/compare the influence of different
      inactivation technologies. METHODS AND RESULTS: Three influencing factors on the
      formation of biofilms are investigated, i.e. growth medium, incubation
      temperature and incubation time, which are three easily controllable
      environmental factors. Optical density measurement and plate counts were used to
      evaluate the adherence and the maturity of the biofilms, respectively. Confocal
      laser scanning microscopy was used to verify most important findings obtained
      with previously mentioned assays. Results indicated that mature and strongly
      adherent L. monocytogenes biofilms are obtained following 13 h of incubation at
      30 degrees C with BHI as growth medium. For S. Typhimurium, an incubation period
      of 19 h at 25 degrees C was required with 20-fold diluted TSB as growth medium.
      CONCLUSIONS: Based on previously mentioned assays, a protocol for the formation
      of reproducible model biofilms was obtained. SIGNIFICANCE AND IMPACT OF THE
      STUDY: The developed model biofilms can be applied as a standard to study
      biofilms (in different research fields) and their subsequent inactivation by
      different methods. In addition, the results of this study could be used to
      control biofilm formation (e.g. by setting a maximum allowed surface
      temperature).

PMID- 30117655
TI  - Thermoelectric SnTe with Band Convergence, Dense Dislocations, and Interstitials
      through Sn Self-Compensation and Mn Alloying.
AB  - SnTe is known as an eco-friendly analogue of PbTe without toxic elements.
      However, the application potentials of pure SnTe are limited because of its high
      hole carrier concentration derived from intrinsic Sn vacancies, which lead to a
      high electrical thermal conductivity and low Seebeck coefficient. In this study,
      Sn self-compensation and Mn alloying could significantly improve the Seebeck
      coefficients in the whole temperature range through simultaneous carrier
      concentration optimization and band engineering, thereby leading to a large
      improvement of the power factors. Combining precipitates and atomic-scale
      interstitials due to Mn alloying with dense dislocations induced by long time
      annealing, the lattice thermal conductivity is drastically reduced. As a result,
      an enhanced figure of merit (ZT) of 1.35 is achieved for the composition of
      Sn0.94 Mn0.09 Te at 873 K and the ZTave from 300 to 873 K is boosted to 0.78,
      which is of great significance for practical application. Hitherto, the ZTmax and
      ZTave of this work are the highest values among all single-element-doped SnTe
      systems.

PMID- 30117656
TI  - Cu-Based Nanoparticles as Emerging Environmental Catalysts.
AB  - This account provides an overview of current research activities on nanoparticles
      containing the earth-abundant and inexpensive element copper (Cu) and Cu-based
      nanoparticles, especially in the field of environmental catalysis. The different
      synthetic strategies with possible modification of the chemical/ physical
      properties of these nanoparticles using such strategies and/or conditions to
      improve catalytic activity are presented. The design and development of support
      and/or bimetallic systems (e. g., alloys, intermetallic, etc.) are also included.
      Herein, we report synthetic approaches of Cu and Cu-based nanoparticles
      (monometallic copper, bimetallic copper and copper (II) oxide
      nanoparticles/nanostructures) and impregnation of such nanoparticles onto support
      material (e. g., Co3 O4 nanostructure), along with their applications as
      environmental catalyst for various oxidation and reduction reactions. Finally,
      this account provides necessary advances and perspectives of Cu-based
      nanoparticles in the environmental catalysis.

PMID- 30117657
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 32/2018.

PMID- 30117658
TI  - Anatomical variations in the first extensor compartment: a cadaver study.
AB  - BACKGROUND: Anatomical variations in the first extensor compartment are
      associated with the pathogenesis of de Quervain's disease. Here, we report two
      novel anatomical variations of the first extensor compartment. METHODS: The
      wrists of two adult cadavers were dissected to reveal the anatomical variations
      in the first extensor compartment. RESULTS: In one of the cadavers, no septum was
      present in the first extensor compartment. However, the extensor pollicis brevis
      tendon and its proximal muscle belly were absent. The abductor pollicis longus
      (APL) tendon had multiple slips, and one of them inserted on the dorsal base of
      the proximal thumb phalanx. In another cadaver, a septum was present in the first
      extensor compartment. One of the multiple APL tendon slips ran into the septum
      alongside the extensor pollicis brevis tendon for 4 mm, which then exited the
      septum and inserted into the base of the first phalanx together with the APL
      tendon. CONCLUSION: Our findings may help to improve the awareness of the
      anatomical variations in the first extensor compartment.

PMID- 30117659
TI  - A pilot study evaluating adaptive closed-loop fluid resuscitation during states
      of absolute and relative hypovolemia in dogs.
AB  - OBJECTIVE: To evaluate and determine the performance of a partially automated as
      well as a fully automated closed-loop fluid resuscitation system during states of
      absolute and relative hypovolemia. DESIGN: Prospective experimental trial.
      SETTING: Research laboratory. ANIMALS: Five adult Beagle dogs. METHODS:
      Isoflurane anesthetized mechanically ventilated dogs were subjected to absolute
      hypovolemia (controlled: 2 trials; uncontrolled: 3 trials), relative hypovolemia
      (2 trials), and the combination of relative and absolute controlled hypovolemia
      (2 trials). Controlled and uncontrolled hypovolemia were produced by withdrawing
      blood from the carotid or femoral artery. Relative hypovolemia was produced by
      increasing the isoflurane concentration (1 trial) or by infusion of intravenous
      sodium nitroprusside (1 trial). Relative hypovolemia combined with controlled
      absolute hypovolemia was produced by increasing the isoflurane concentration (1
      trial) and infusion of IV sodium nitroprusside (1 trial). Hemodynamic parameters
      including stroke volume variation (SVV) were continuously monitored and recorded
      in all dogs. A proprietary closed-loop fluid administration system based on fluid
      distribution and compartmental dynamical systems administered a continuous
      infusion of lactated Ringers solution in order to restore and maintain SVV to a
      predetermined target value. MEASUREMENTS AND MAIN RESULTS: A total of 9
      experiments were performed on 5 dogs. Hemodynamic parameters deteriorated and SVV
      increased during controlled or uncontrolled hypovolemia, relative hypovolemia,
      and during relative hypovolemia combined with controlled hypovolemia. Stroke
      volume variation was restored to baseline values during closed-loop fluid
      infusion. CONCLUSIONS: Closed-loop fluid administration based on IV fluid
      distribution and compartmental dynamical systems can be used to provide goal
      directed fluid therapy during absolute or relative hypovolemia in mechanically
      ventilated isoflurane anesthetized dogs.

PMID- 30117660
TI  - Biological control of Pseudomonas syringae pv. aptata on sugar beet with Bacillus
      pumilus SS-10.7 and Bacillus amyloliquefaciens (SS-12.6 and SS-38.4) strains.
AB  - AIM: Assessment of biological control of Pseudomonas syringae pv. aptata using
      crude lipopeptide extracts (CLEs) of two Bacillus amyloliquefaciens strains (SS
      12.6 and SS-38.4) and one Bacillus pumilus strain (SS-10.7). METHODS AND RESULTS:
      The minimum inhibitory concentration (MIC) of CLEs and their combinations against
      the pathogen and potential interaction between the extracts were determined in
      vitro. The most effective antibacterial activity was achieved with the CLE from
      B. amyloliquefaciens SS-12.6, with an MIC value of 0.63 mg ml-1 . Interactions
      between CLE combinations were mostly indifferent. The biocontrol potential of
      CLEs, mixtures of CLEs, and cell culture of B. amyloliquefaciens SS-12.6 was
      tested on sugar beet plants inoculated with P. syringae pv. aptata P53. The best
      result in inhibiting the appearance of tissue necrosis (up to 92%) was achieved
      with B. amyloliquefaciens SS-12.6 cell culture. CONCLUSION: This work
      demonstrated significant biocontrol potential of the CLE and cell culture of B.
      amyloliquefaciens SS-12.6 which successfully suppress leaf spot disease severity
      on sugar beet plants. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of
      biocontrol of sugar beet emerging pathogen will contribute to growers in terms of
      alternative disease control management. This study represents first assessment of
      biological control of P. syringae pv. aptata.

PMID- 30117661
TI  - Methodological issue on mixed-methods study of reported clinical cases of
      undesirable events, medical errors, and near misses in health care.

PMID- 30117662
TI  - Reply to letter to the editor titled "Methodological issue on mixed-methods study
      of reported clinical cases of undesirable events, medical errors, and near misses
      in health care".

PMID- 30117663
TI  - Corrigendum.

PMID- 30117664
TI  - Editorial introduction: The implications of translational neuroscience for
      clinical practice and its evaluation.

PMID- 30117665
TI  - Pulmonary sequestration mimicking lung abscess in old age.

PMID- 30117666
TI  - Tissue oxygen saturation in dogs with acute hemorrhage.
AB  - OBJECTIVE: To evaluate initial tissue hemoglobin oxygen saturation (StO2 ) in
      dogs presenting to an emergency room (ER) for acute hemorrhage. DESIGN:
      Prospective, observational study. SETTING: University veterinary teaching
      hospital. ANIMALS: Thirty-eight dogs with acute hemorrhage were enrolled between
      July 2009 and October 2010. Seventy-eight normal dogs from a previous
      observational study were included to represent healthy controls ("no shock").
      INTERVENTIONS: Tissue oxygen saturation measurement was obtained at enrollment on
      dogs presented to the ER for acute hemorrhage. Baseline clinicopathologic (CBC,
      serum biochemical profile, prothrombin time, and activated partial thromboplastin
      time) and physiologic (plasma lactate concentration, venous blood gas, blood
      pressure, and hemoglobin oxygen saturation by pulse oximetry) data were recorded
      from all patients with hemorrhage. An ER clinician blinded to the StO2 value
      guided patient management. Patient survival to discharge from the hospital in the
      study group was recorded. Once data collection was complete, 3 emergency and
      critical care clinicians blinded to the StO2 data retrospectively classified
      patients into 1 of 4 shock categories (no shock, mild, moderate, or severe
      shock). MEASUREMENTS AND MAIN RESULTS: The historical group of healthy dogs had
      higher StO2 concentrations compared to the dogs classified with shock at all 3
      levels (mild, moderate, and severe, P = 0.0006, <0.0001, and 0.0018,
      respectively); however, there was no statistical difference in StO2 between the
      levels of shock. A cut-off StO2 value of 87.6% identified a patient as having
      shock (area under the curve: 0.824, 95% confidence interval 0.749, 0.899).
      CONCLUSIONS: Dogs with hemorrhagic shock have lower StO2 than a population of
      healthy dogs.

PMID- 30117667
TI  - Epigenetic silenced miR-125a-5p could be self-activated through targeting Suv39H1
      in gastric cancer.
AB  - Emerging evidence suggests that microRNAs (miRNAs) serve an important role in
      tumorigenesis and development. Although the low expression of miR-125a-5p in
      gastric cancer has been reported, the underlying mechanism remains unknown. In
      the current study, the low expression of miR-125a-5p in gastric cancer was
      verified in paired cancer tissues and adjacent non-tumour tissues. Furthermore,
      the GC islands in the miR-125a-5p region were hypermethylated in the tumour
      tissues. And the hypermethylation was negatively correlated with the miR-125a-5p
      expression. Target gene screening showed that the histone methyltransferase
      Suv39H1 was one of the potential target genes. In vitro studies showed that miR
      125a-5p could directly suppress the Suv39H1 expression and decrease the H3K9me3
      levels. On the other hand, the Suv39H1 could induce demethylation of miR-125a-5p,
      resulting in re-activation of miR-125a-5p. What is more, overexpessing miR-125a
      5p could also self-activate the silenced miR-125a-5p in gastric cancer cells,
      which suppressed cell migration, invasion and proliferation in vitro and
      inhibited cancer progression in vivo. Thus, we uncovered here that the epigenetic
      silenced miR-125a-5p could be self-activated through targeting Suv39H1 in gastric
      cancer, suggesting that miR-125a-5p might be not only the potential prognostic
      value as a tumour biomarker but also potential therapeutic targets in gastric
      cancer.

PMID- 30117668
TI  - Sulforaphane absorption and histone deacetylase activity following single dosing
      of broccoli sprout supplement in normal dogs.
AB  - The role of epigenetic alterations during cancer has gained increasing attention
      and has resulted in a paradigm shift in our understanding of mechanisms leading
      to cancer susceptibility. Sulforaphane (SFN) is a naturally occurring
      isothiocyanate derived from the precursor glucosinolate, glucoraphanin (GFN),
      which is found in cruciferous vegetables such as broccoli. Sulforaphane has been
      shown to suppress tumour growth by several mechanisms including inhibiting
      histone deacetylases. The objective of this study was to provide a detailed
      analysis of sulforaphane absorption following a single oral dose of a broccoli
      sprout supplement in normal dogs. A single dose of broccoli sprout supplement
      (with active myrosinase) was orally administered to 10 healthy adult dogs. Blood
      and urine samples were collected prior to dosing, and at various time points post
      dosing. Plasma total SFN metabolite levels peaked at 4 h post-consumption and
      were cleared by 24 h post-consumption. Urinary SFN metabolites peaked at 4 h post
      consumption, and remained detectable at 24 and 48 h post-supplement consumption.
      A trend for decrease in histone deacetylase activity was observed at 1 h post
      consumption and a significant decrease was observed at 24 h post-consumption. The
      data presented herein indicate that oral SFN is absorbed in dogs, SFN metabolites
      are detectable in plasma and urine post-dosing, and SFN and its metabolites have
      some effect on histone deacetylase activity following a single dose.

PMID- 30117669
TI  - Detecting tumour response and predicting resectability after neoadjuvant therapy
      for borderline resectable and locally advanced pancreatic cancer.
AB  - BACKGROUND: This systematic review aimed to determine the accuracy of imaging
      modalities to predict resectability and R0 resection for borderline resectable
      (BRPC) or locally advanced pancreatic cancer (LAPC) after neoadjuvant therapy
      (NAT). METHODS: A systematic search of major databases was performed in
      accordance with Preferred Reporting Items for Systematic Reviews and Meta
      Analyses guidelines. RESULTS: Fifteen studies identified 995 patients of which
      683 had BRPC and 312 LAPC. Computed tomography (CT) scan was the most common
      modality for re-staging (n = 14), followed by positron emission tomography (PET)
      CT (n = 3) and endosonography (EUS) (n = 2). Stable disease on RECIST criteria
      was found in 67% of patients (range 53-80%) with 20% demonstrating reduction in
      tumour size. A total of 60% of patients underwent surgery post-NAT (range 31-85%)
      with a R0 rate of 88% (range 57-100%). Accuracy for predicting R0 resectability
      and T-stage on CT scan was 71 and 49%. A reduction in SUVmax on PET-CT and
      reduction of tumour stiffness on EUS elastography positively correlated with
      resectability. CONCLUSIONS: More than half the patients undergo resection post
      NAT for LAPC and BRPC. Stable, or reduction of, tumour disease may predict
      resectability. Reduction in tumour SUVmax on PET-CT and decreased tumour
      stiffness on EUS elastography may be potential markers of NAT response and
      resectability.

PMID- 30117670
TI  - Shunts and bypasses for portal hypertension: Making the right choice.

PMID- 30117671
TI  - The middle hepatic vein controversy: Art and science.

PMID- 30117673
TI  - Signet cell carcinoma of the colon: a rare presentation to a rural surgical
      service.

PMID- 30117672
TI  - Lycium barbarum polysaccharides restore adverse structural remodelling and
      cardiac contractile dysfunction induced by overexpression of microRNA-1.
AB  - MicroRNA-1 (miR-1) stands out as the most prominent microRNA (miRNA) in
      regulating cardiac function and has been perceived as a new potential therapeutic
      target. Lycium barbarum polysaccharides (LBPs) are major active constituents of
      the traditional Chinese medicine based on L. barbarum. The purpose of this study
      was to exploit the cardioprotective effect and molecular mechanism of LBPs
      underlying heart failure. We found that LBPs significantly reduced the expression
      of myocardial miR-1. LBPs improved the abnormal ECG and indexes of cardiac
      functions in P-V loop detection in transgenic (Tg) mice with miR-1
      overexpression. LBPs recovered morphological changes in sarcomeric assembly,
      intercalated disc and gap junction. LBPs reversed the reductions of CaM and
      cMLCK, the proteins targeted by miR-1. Similar trends were also obtained in their
      downstream effectors including the phosphorylation of MLC2v and both total level
      and phosphorylation of CaMKII and cMyBP-C. Collectively, LBPs restored adverse
      structural remodelling and improved cardiac contractile dysfunction induced by
      overexpression of miR-1. One of the plausible mechanisms was that LBPs down
      regulated miR-1 expression and consequently reversed miR-1-induced repression of
      target proteins relevant to myocardial contractibility. LBPs could serve as a
      new, at least a very useful adjunctive, candidate for prevention and therapy of
      heart failure.

PMID- 30117674
TI  - Characterization of three new HLA Class I Alleles in Chinese individuals, HLA
      B*46:68,-B*46:71,-B*46:72.
AB  - Three new HLA class I alleles were described in the Chinese population. HLA
      B*46:68,-B*46:71,-B*46:72 alleles differ from HLA-B*46:01:01 by a single
      nucleotide substitution at position 485C>T, 484A>G, 299T>A respectively.

PMID- 30117675
TI  - Appropriate use of dressings containing nanocrystalline silver to support
      antimicrobial stewardship in wounds.
AB  - Antimicrobial resistance is an ever-increasing global concern, with the era of
      untreatable infection becoming a reality. Wound care is no exception, with
      increasing issues of antibiotic-resistant infections across different wound types
      and care settings. Antibiotic resistance and stewardship have been the priority
      for most strategic interventions so far; however, in wound care, alternative or
      supplementary strategies using antiseptics should be considered. Antiseptics such
      as silver can provide effective cidal activity across a broad range of wound
      pathogens, assuming they are used at the correct level for an appropriate
      duration. Evidence summarised in this manuscript suggests that effective
      antiseptics, such as nanocrystalline silver, have an increasing body of evidence
      in support of their use to minimise transmission of antibiotic-resistant
      organisms as part of institutional infection control procedures and, in addition,
      through appropriate early use and stewardship on local wound infections, in
      conjunction with local procedures, to minimise the need for systemic antibiotic
      therapy. Engagement, alignment, and collaboration between wound care
      professionals and wider related teams and governments on antimicrobial
      stewardship, and the potential role of antiseptics within this, will help to
      generate further evidence for such interventions in the fight against
      antimicrobial-resistant infections in wound care.

PMID- 30117677
TI  - LiCl as Phase-Transfer Catalysts to Synthesize Thin Co2 P Nanosheets for Oxygen
      Evolution Reaction.
AB  - Inorganic salts have been widely studied as templates for the synthesis of 2D
      layer structures. However, these salts normally can only serve as templates
      without any catalytic activity. Here, we report that LiCl used for the synthesis
      of ultrathin nanosheets not only serves as template for the synthesis of
      ultrathin Co2 P nanosheets with a thickness of 0.7 nm but also acts as a catalyst
      that induces the phase-transfer from CoP to Co2 P. The Co2 P nanosheets have a
      high electrochemical performance for oxygen evolution reaction.

PMID- 30117676
TI  - From fever to immunity: A new role for IGFBP-6?
AB  - Fever is a fundamental response to infection and a hallmark of inflammatory
      disease, which has been conserved and shaped through millions of years of natural
      selection. Although fever is able to stimulate both innate and adaptive immune
      responses, the very nature of all the molecular thermosensors, the timing and the
      detailed mechanisms translating a physical trigger into a fundamental biological
      response are incompletely understood. Here we discuss the consequence of
      hyperthermic stress in dendritic cells (DCs), and how the sole physical input is
      sensed as an alert stimulus triggering a complex transition in a very narrow
      temporal window. Importantly, we review recent findings demonstrating the
      significant and specific changes discovered in gene expression and in the
      metabolic phenotype associated with hyperthermia in DCs. Furthermore, we discuss
      the results that support a model based on a thermally induced autocrine
      signalling, which rewires and sets a metabolism checkpoint linked to immune
      activation of dendritic cells. Importantly, in this context, we highlight the
      novel regulatory functions discovered for IGFBP-6 protein: induction of
      chemotaxis; capacity to increase oxidative burst and degranulation of
      neutrophils, ability to induce metabolic changes in DCs. Finally, we discuss the
      role of IGFBP-6 in autoimmune disease and how novel mechanistic insights could
      lead to exploit thermal stress-related mechanisms in the context of cancer
      therapy.

PMID- 30117679
TI  - Genome-Scale Metabolic Reconstruction of Actinomycetes for Antibiotics
      Production.
AB  - Systems biology approaches are increasingly applied to explore the potential of
      actinomycetes for the discovery and optimal production of antibiotics. In
      particular, genome-scale metabolic models (GEMs) of various actinomycetes are
      reconstructed at a faster rate in recent years, which has opened avenues to study
      interaction between primary and secondary metabolism at systems level, and to
      predict gene manipulation targets for overproduction of important antibiotics.
      Here, the status of actinomycetes' GEMs and their applications for designing
      antibiotics-overproducing strains are presented. Despite advances in the practice
      of GEM reconstruction, actinomycetes' GEMs still remain incomplete in describing
      a full set of biosynthetic pathways of secondary metabolites. As to the GEM-based
      strategies, various simulation methods are deployed to better describe secondary
      metabolism by introducing changes in constraints and/or objective function as
      well as by using omics data. Gene manipulation targeting algorithms developed for
      metabolic engineering of model organisms have also been actively applied to
      actinomycetes for the antibiotics production. Further consideration of
      computational resources dedicated to secondary metabolites in addition with
      automated GEM reconstruction tools will further upgrade GEMs of actinomycetes for
      antibiotics discovery and development.

PMID- 30117678
TI  - Long non-coding RNAs in brain tumours: Focus on recent epigenetic findings in
      glioma.
AB  - Glioma biology is a major focus in tumour research, primarily due to the
      aggressiveness and high mortality rate of its most aggressive form, glioblastoma.
      Progress in understanding the molecular mechanisms behind poor prognosis of
      glioblastoma, regardless of treatment approaches, has changed the classification
      of brain tumours after nearly 100 years of relying on anatomopathological
      criteria. Expanding knowledge in genetic, epigenetic and translational medicine
      is also beginning to contribute to further elucidating molecular dysregulation in
      glioma. Long non-coding RNAs (lncRNAs) and their main representatives, large
      intergenic non-coding RNAs (lincRNAs), have recently been under scrutiny in
      glioma research, revealing novel mechanisms of pathogenesis and reinforcing
      others. Among those confirmed was the reactivation of events significant for
      foetal brain development and neuronal commitment. Novel mechanisms of tumour
      suppression and activation of stem-like behaviour in tumour cells have also been
      examined. Interestingly, these processes involve lncRNAs that are present both
      during normal brain development and in brain malignancies and their reactivation
      might be explained by epigenetic mechanisms, which we discuss in detail in the
      present review. In addition, the review discusses the lncRNAs-induced changes, as
      well as epigenetic changes that are consequential for tumour formation,
      affecting, in turn, the expression of various types of lncRNAs.

PMID- 30117682
TI  - Go with the Flow-Microfluidics Approaches for Amyloid Research.
AB  - The rapid development of cost-efficient microfluidic devices has received
      tremendous attention from scientists of diverse fields. The growing potential of
      utilizing microfluidic platforms has further advanced the ability to integrate
      existing technology into microfluidic devices. Thus, allowing scientists to
      approach questions in fundamental fields, such as amyloid research, using new and
      otherwise unachievable conditions. Amyloids are associated with neurodegeneration
      and are in the forefront of many research efforts worldwide. The newly emerged
      microfluidic technology can serve as a novel research tool providing a platform
      for developing new methods in this field. In this review, we summarize the recent
      progress in amyloid research using microfluidic approaches. These approaches are
      driven from various fields, including physical chemistry, electrochemistry,
      biochemistry, and cell biology. Moreover, the new insights into novel
      microfluidic approaches for amyloid research reviewed here can be easily modified
      for other research interests.

PMID- 30117680
TI  - Bradykinin-mediated Ca2+ signalling regulates cell growth and mobility in human
      cardiac c-Kit+ progenitor cells.
AB  - Our recent study showed that bradykinin increases cell cycling progression and
      migration of human cardiac c-Kit+ progenitor cells by activating pAkt and pERK1/2
      signals. This study investigated whether bradykinin-mediated Ca2+ signalling
      participates in regulating cellular functions in cultured human cardiac c-Kit+
      progenitor cells using laser scanning confocal microscopy and biochemical
      approaches. It was found that bradykinin increased cytosolic free Ca2+ ( Cai2+ )
      by triggering a transient Ca2+ release from ER IP3Rs followed by sustained Ca2+
      influx through store-operated Ca2+ entry (SOCE) channel. Blockade of B2 receptor
      with HOE140 or IP3Rs with araguspongin B or silencing IP3R3 with siRNA abolished
      both Ca2+ release and Ca2+ influx. It is interesting to note that the bradykinin
      induced cell cycle progression and migration were not observed in cells with
      siRNA-silenced IP3R3 or the SOCE component TRPC1, Orai1 or STIM1. Also the
      bradykinin-induced increase in pAkt and pERK1/2 as well as cyclin D1 was reduced
      in these cells. These results demonstrate for the first time that bradykinin
      mediated increase in free Cai2+ via ER-IP3R3 Ca2+ release followed by Ca2+ influx
      through SOCE channel plays a crucial role in regulating cell growth and migration
      via activating pAkt, pERK1/2 and cyclin D1 in human cardiac c-Kit+ progenitor
      cells.

PMID- 30117683
TI  - Ruckblick auf den 63. Deutschen STI-Kongress 2018 in Bochum.

PMID- 30117684
TI  - Lenalidomid zur Behandlung von rezidivierenden oralen Apthten bei Morbus
      Adamantiades-Behcet.

PMID- 30117681
TI  - Signalling mechanisms that regulate metabolic profile and autophagy of acute
      myeloid leukaemia cells.
AB  - Acute myeloid leukaemia (AML) comprises a heterogeneous group of hematologic
      neoplasms characterized by diverse combinations of genetic, phenotypic and
      clinical features representing a major challenge for the development of targeted
      therapies. Metabolic reprogramming, mainly driven by deregulation of the nutrient
      sensing pathways as AMPK, mTOR and PI3K/AKT, has been associated with cancer
      cells, including AML cells, survival and proliferation. Nevertheless, the role of
      these metabolic adaptations on the AML pathogenesis is still controversial. In
      this work, the metabolic status and the respective metabolic networks operating
      in different AML cells (NB-4, HL-60 and KG-1) and their impact on autophagy and
      survival was characterized. Data show that whereas KG-1 cells exhibited
      preferential mitochondrial oxidative phosphorylation metabolism with constitutive
      co-activation of AMPK and mTORC1 associated with increased autophagy, NB-4 and HL
      60 cells displayed a dependent glycolytic profile mainly associated with
      AKT/mTORC1 activation and low autophagy flux. Inhibition of AKT is disclosed as a
      promising therapeutical target in some scenarios while inhibition of AMPK and
      mTORC1 has no major impact on KG-1 cells' survival. The results highlight an
      exclusive metabolic profile for each tested AML cells and its impact on
      determination of the anti-leukaemia efficacy and on personalized combinatory
      therapy with conventional and targeted agents.

PMID- 30117685
TI  - Multiple "Angiome" bei einem 14 Monate alten Kleinkind.

PMID- 30117687
TI  - Hamodialyse verbessert die Feuchtigkeit und Sebumsekretion, aber nicht die
      Elastizitat der Haut bei Patienten mit einer chronischen Nierenerkrankung.

PMID- 30117686
TI  - Frontal fibrosing alopecia - review of recent case reports and case series in
      PubMed.
AB  - BACKGROUND: In his initial publication of frontal fibrosing alopecia (FFA) in
      1994, Steven Kossard included six postmenopausal women. A type of cicatricial
      alopecia, FFA is clinically characterized by frontotemporal hairline recession
      and loss of eyebrows. In recent years, there has been an increasing number of
      case reports of FFA in both premenopausal women and men. STUDY OBJECTIVE: Review
      and analysis of the literature on FFA with regard to epidemiology, associated
      disorders, disease presentation, diagnosis and treatment. METHODS AND MATERIAL:
      We conducted a Pubmed database search for case reports and case series on FFA.
      Overall, we reviewed and analyzed data from 68 articles, including 932 patients.
      Apart from epidemiological data such as age, gender or ethnicity, we also
      assessed other aspects such as predilection sites, associated skin lesions,
      comorbidities, drugs and treatment response as well as the diagnostic
      significance of autoantibodies. RESULTS: While we were able to confirm and more
      accurately define some of the data published in the literature, we were unable to
      reproduce certain assumptions that had previously been made. The high coincidence
      of FFA and thyroid disease we found in our analysis is particularly significant.
      CONCLUSIONS: The present study provides the most comprehensive review to date of
      published cases of FFA.

PMID- 30117688
TI  - Chronisch pruriginose Papeln Jahre nach Aufenthalt in Kamerun.

PMID- 30117689
TI  - Schwellung der Handgelenke, Arthralgie, Photosensibilitat und erworbene
      generalisierte Cutis-laxa-artige Manifestation einer Lepra.

PMID- 30117690
TI  - Die Entwicklung der Therapie des Hautkrebses geht weiter - Bericht von der
      Jahrestagung der American Society of Clinical Oncology (ASCO) in Chicago vom
      31.5.- 3.6. 2018.

PMID- 30117691
TI  - In Memoriam Professor Dr. Erwin Schopf.

PMID- 30117692
TI  - Positionspapier: Telemedizin in der Berufsdermatologie - Aktueller Stand und
      Perspektiven.

PMID- 30117693
TI  - Pseudoaneurysmen als mogliche Komplikation nach Dermatochirurgie im Gesicht.

PMID- 30117694
TI  - Therapierefraktare Pityriasis rubra pilaris mit gutem Ansprechen auf Ustekinumab.

PMID- 30117695
TI  - Die Fortbildungstage am Arlberg - Ein Musterbeispiel einer gelungenen
      transnationalen dermatochirurgischen Fortbildung.

PMID- 30117696
TI  - Gedenktafel fur Albrecht Scholz.

PMID- 30117697
TI  - Schleimhautsubstrate identifizieren erfolgreich das Autoantigen bei einem
      Schleimhautpemphigoid.

PMID- 30117698
TI  - Frontal fibrosierende Alopezie - Review aktueller Fallbeispiele und Fallserien in
      PubMed.

PMID- 30117700
TI  - Disseminierte erythematose Papeln und Nodi.

PMID- 30117699
TI  - Lebensqualitat und Behandlungsziele bei Psoriasis aus Patientensicht: Ergebnisse
      eines osterreichweiten Querschnitt-Survey.
AB  - HINTERGRUND: Patienten mit Psoriasis sind mit einer krankheitsbedingten
      Einschrankung ihrer Lebensqualitat konfrontiert, weshalb einer hochqualitativen
      dermatologischen Versorgung ein besonderer Stellenwert zukommt. PATIENTEN UND
      METHODIK: Wir fuhrten einen bundesweiten Querschnitt-Survey in Osterreich
      (BQSAustria Psoriasis 2014/2015) mit dem Schwerpunkt auf Lebensqualitat und
      Therapiezufriedenheit bei Patienten mit Psoriasis in dermatologischer Behandlung
      vorwiegend an Zentren mit uberwiegend tertiaren Versorgungsaufgaben durch.
      ERGEBNISSE: 70,2 % der 1184 befragten Patienten berichtete uber eine
      eingeschrankte Lebensqualitat (DLQI 2-5: 29,4 %; 6-10: 19,3 %; 11-15: 11,5 %; 16
      20: 5,2 % und > 20: 4,9 %) trotz Behandlung innerhalb der letzten vier Wochen
      (mit lokaler Therapie in 88,2 % und/oder systemischer Therapie in 38,7 % der
      Falle). Mit den verabreichten Therapien konnte im Durchschnitt kein einziges von
      25 definierten subjektiven Behandlungszielen im gewunschten Ausmabeta erreicht
      werden. So litten 82,2 % der Patienten trotz Behandlung weiter unter Juckreiz,
      wobei statistisch hochsignifikante Assoziationen mit einem schlechten
      Gesundheitszustand in der letzten Woche (Spear-man-Rangkorrelation; p = 1.1e-45),
      dem Ausmabeta des psoriatischen Korperoberflachenbefalls (p = 3.2e-11) und
      Kopfhautbefalls (p = 3.2e-11) sowie Schmerzen (p = 2.3e-22) vorlagen. Die
      Behandlung mit einem Biologikum war mit einer signifikant hoheren
      Patientenzufriedenheit verbunden (Wilcoxon-Test, p = 2.0e-16).
      SCHLUSSFOLGERUNGEN: Die Lebensqualitat der meisten osterreichischen Patienten mit
      Psoriasis in dermatologischer Versorgung ist krankheitsbedingt beeintrachtigt,
      und es besteht ein Verbesserungspotenzial bei der Umsetzung von
      Behandlungszielen.

PMID- 30117702
TI  - Rechtlicher Stellenwert der sequenziellen digitalen Dermatoskopie - Bedeutung
      dermatologischer Leitlinien.

PMID- 30117701
TI  - Die Sicht von Medizinstudierenden auf das Fach Dermatologie.

PMID- 30117703
TI  - Nonmelanoma skin cancer - from actinic keratosis to cutaneous squamous cell
      carcinoma.
AB  - Actinic keratoses (AKs) are defined as intraepithelial proliferation of atypical
      keratinocytes. Given their potential for progression to invasive squamous cell
      carcinoma, they may eventually evolve into a life-threatening disease. In recent
      decades, there has been a significant increase in the incidence of AKs, primarily
      due to changes in recreational activities and demographic trends in
      industrialized countries. As it is currently impossible to predict if and when a
      given AK might progress to invasive carcinoma, rigorous treatment of field
      cancerization is a key component in preventing potential progression. In addition
      to a broad armamentarium of procedures as well as pharmaceutical treatment
      options, primary prevention through diligent UV protection likewise plays a
      crucial role. New clinical, histomorphological, or molecular classifications are
      needed to be able to reliably stratify patients based on their individual risk.
      Especially in light of socio-economic aspects, such a step might prevent over-
      and undertreatment of an ever-growing patient population and help develop
      treatment concepts based on individual patient needs.

PMID- 30117704
TI  - Kongresskalender 2018.

PMID- 30117706
TI  - Atopisches Ekzem: die Basis nicht vergessen!

PMID- 30117705
TI  - Mucosal substrates successfully identify the autoantigen in a case of mucous
      membrane pemphigoid.

PMID- 30117707
TI  - Basistherapie bei atopischer Dermatitis - Neues und Bewahrtes.

PMID- 30117708
TI  - Nichtmelanozytare Hauttumoren - von der aktinischen Keratose bis zum
      Plattenepithelkarzinom.

PMID- 30117709
TI  - Mehrere pigmentierte Lasionen der Glans penis nach Zirkumzision.

PMID- 30117710
TI  - Blasenbildung an den Handen nach Manikure in einem Nagelstudio.

PMID- 30117712
TI  - Forschungspreis der Jorg Wolff-Stiftung - Arnold Rikli-Preis 2018.

PMID- 30117713
TI  - Swollen hand joints, arthralgia, photosensitivity and generalized acquired cutis
      laxa-like presentation of leprosy.

PMID- 30117711
TI  - Quality of life and treatment goals in psoriasis from the patient perspective:
      results of an Austrian cross-sectional survey.
AB  - BACKGROUND: Patients with psoriasis experience impairment in quality of life.
      Thus, high-quality dermatological care is of particular importance. PATIENTS AND
      METHODS: We performed a nationwide cross-sectional survey in Austria (BQSAustria
      Psoriasis 2014/2015) with a special focus on quality of life and satisfaction
      with treatment among psoriasis patients predominantly treated at tertiary care
      centers. RESULTS: Overall, 70.2 % of 1,184 patients reported impaired quality of
      life (DLQI 2-5: 29.4 %; 6-10: 19.3 %; 11-15: 11.5 %; 16-20: 5.2 % and > 20: 4.9
      %) despite treatment over the preceding four weeks (topical treatment in 88.2 %
      of cases and/or systemic treatment in 38.7 %). On average, none of the 25 defined
      subjective treatment goals was achieved to a sufficient degree. In particular,
      82.2 % of patients continued to have pruritus despite treatment, which was highly
      significantly associated with a poor general health status over the preceding
      week (Spearman's rank correlation; p  =  1.1e-45), the extent of body surface
      area (p  =  3.2e-11) and scalp area (p  =  3.2e-11) affected, as well as pain (p 
      =  2.3e-22). Treatment with a biologic was significantly correlated with higher
      patient satisfaction (Wilcoxon-Test, p  =  2.0e-16). CONCLUSIONS: Despite
      dermatological care, the majority of Austrian psoriasis patients continues to
      experience impaired quality of life; there is potential for improvement in the
      achievement of treatment goals.

PMID- 30117715
TI  - High-Performance Biosensing Systems Based on Various Nanomaterials as Signal
      Transducers.
AB  - Recently, highly sensitive and selective biosensors have become necessary for
      improving public health and well-being. To fulfill this need, high-performance
      biosensing systems based on various nanomaterials, such as nanoparticles, carbon
      nanomaterials, and hybrid nanomaterials, are developed. Numerous nanomaterials
      show excellent physical properties, including plasmonic, magnetic, catalytic,
      mechanical and fluorescence properties and high electrical conductivities, and
      these unique and beneficial properties have contributed to the fabrication of
      high-performance biosensors with various applications, including in optical,
      electrical, and electrochemical detection platforms. In addition, these
      properties can be transformed to signals for the detection of biomolecules. In
      this review, various types of nanomaterial-based biosensors are introduced, and
      they show high sensitivity and selectivity. In addition, the potential
      applications of these sensors on the biosensing of several types of biomolecules
      are also discussed. These nanomaterials-based biosensing systems provide a
      significant improvement on healthcare including rapid monitoring and early
      detection of infectious disease for public health.

PMID- 30117716
TI  - An evidence-based review of split-thickness skin graft donor site dressings.
AB  - This evidence-based review aimed to identify and evaluate current existing
      evidence relating to the efficacy of dressing materials for spit-thickness skin
      graft donor site wounds in relation to promoting rapid healing and reducing
      patient pain. A comprehensive systematic search of the literature between 2006
      and 2016 identified 35 publications that were included in the review. Based on
      the results of the review, it was found that moist wound-healing products have a
      clear advantage over non-moist products in the reduction of pain and increased
      healing rates. This review concluded that moist wound-healing products are more
      effective than non-moist wound-healing products in reducing pain and promoting
      healing in split-thickness skin graft donor site wounds. A recommendation based
      on this review is that further research examine the role of secondary dressing
      usage in donor site wound management, and the consideration of using more than
      one primary dressing product during the donor site wound-healing process should
      be undertaken.

PMID- 30117717
TI  - Erratum.

PMID- 30117718
TI  - Lower airway disease: Does research fit our practice needs?

PMID- 30117719
TI  - Intratumoral recombinant human interferon alpha-2a and vincristine combination
      therapy in canine transmissible venereal tumour.
AB  - Canine transmissible venereal tumour (CTVT) is a naturally occurring contagious
      neoplasm of dogs located mainly on the external genitalia of both sexes. The
      course of vincristine chemotherapy, the most effective and practical therapy, is
      affected by the immune status of the host. The aim was to investigate recombinant
      human interferon alpha-2a (rhIFNalpha-2a) and vincristine for treatment of CTVT.
      A total of 21 female dogs were included. In group I (n = 9), vincristine (0.025
      mg/kg, IV) was administered weekly. In group II (n = 6), dogs were injected
      intratumorally weekly with 1.5 million IU rhIFNalpha-2a. In group III (n = 6),
      rhIFNalpha-2a and vincristine were combined. No tumour regression was observed
      after three injections of rhIFNalpha-2a in group II and weekly vincristine was
      administered. The number of tumour infiltrating lymphocytes (TILs), mitotic
      figures and apoptotic cells were counted in subsequent incisional tumour
      biopsies. The Kaplan-Meier Method was used to analyse survival using complete
      tumour regression as the outcome and Breslow Test was used for comparison of
      survival curves. Differences in TILs, cell proliferation and apoptosis between
      groups were assessed by analysis of covariance. Complete regression was observed
      in all animals included. Mean duration of vincristine treatment for complete
      regression was shorter in group II (3.50 weeks, 95% CI, 3.06-3.94, P < 0.05) and
      group III (3.17 weeks, 95% CI, 2.84-3.49, P < 0.01) compared to group I (5.11
      weeks, 95% CI, 4.42-5.80). Vincristine and rhIFNalpha-2a combination increased
      TILs in CTVT biopsies compared to vincristine treatment (P = 0.017) and
      vincristine treatment after rhIFNalpha-2a (P = 0.049). Vincristine treatment
      after rhIFNalpha-2a (Group II; P < 0.001) and rhIFNalpha-2a and vincristine
      combination (Group III; P < 0.001) decreased apoptosis. The results indicate that
      intratumoral rhIFNalpha-2a treatment alone is not effective in CTVT. However,
      combination of rhIFNalpha-2a and vincristine shortens the duration of treatment
      compared to vincristine therapy.

PMID- 30117722
TI  - Spotlights on our sister journals: Angew. Chem. Int. Ed. 30/2018.

PMID- 30117721
TI  - Multiple myocardial bridges associated with left-ventricular dysfunction,
      intermittent left bundle branch block, and cardiac memory: A case report.
AB  - Myocardial bridges are a congenital anomaly in which a segment of the coronary
      artery takes a "tunneled" intramuscular course. Few reports have associated
      myocardial bridges with left-ventricular dysfunction in patients with ischemia.
      Intermittent left bundle branch block is a conduction disturbance that has been
      described to be associated with myocardial bridges and cardiac memory. This study
      reports unusual associations of multiple myocardial bridges, angina, left
      ventricular dysfunction, intermittent left bundle branch block, and cardiac
      memory.

PMID- 30117720
TI  - Empagliflozin reduces Ca/calmodulin-dependent kinase II activity in isolated
      ventricular cardiomyocytes.
AB  - AIMS: The EMPA-REG OUTCOME study showed reduced mortality and hospitalization due
      to heart failure (HF) in diabetic patients treated with empagliflozin.
      Overexpression and Ca2+ -dependent activation of Ca2+ /calmodulin-dependent
      kinase II (CaMKII) are hallmarks of HF, leading to contractile dysfunction and
      arrhythmias. We tested whether empagliflozin reduces CaMKII- activity and
      improves Ca2+ -handling in human and murine ventricular myocytes. METHODS AND
      RESULTS: Myocytes from wild-type mice, mice with transverse aortic constriction
      (TAC) as a model of HF, and human failing ventricular myocytes were exposed to
      empagliflozin (1 MUmol/L) or vehicle. CaMKII activity was assessed by CaMKII
      histone deacetylase pulldown assay. Ca2+ spark frequency (CaSpF) as a measure of
      sarcoplasmic reticulum (SR) Ca2+ leak was investigated by confocal microscopy.
      [Na+ ]i was measured using Na+ /Ca2+ -exchanger (NCX) currents (whole-cell patch
      clamp). Compared with vehicle, 24 h empagliflozin exposure of murine myocytes
      reduced CaMKII activity (1.6 +/- 0.7 vs. 4.2 +/- 0.9, P < 0.05, n = 10 mice), and
      also CaMKII-dependent ryanodine receptor phosphorylation (0.8 +/- 0.1 vs. 1.0 +/-
      0.1, P < 0.05, n = 11 mice), with similar results upon TAC. In murine myocytes,
      empagliflozin reduced CaSpF (TAC: 1.7 +/- 0.3 vs. 2.5 +/- 0.4 1/100 MUm-1  s-1 ,
      P < 0.05, n = 4 mice) but increased SR Ca2+ load and Ca2+ transient amplitude.
      Importantly, empagliflozin also significantly reduced CaSpF in human failing
      ventricular myocytes (1 +/- 0.2 vs. 3.3 +/- 0.9, P < 0.05, n = 4 patients), while
      Ca2+ transient amplitude was increased (F/F0 : 0.53 +/- 0.05 vs. 0.36 +/- 0.02, P
      < 0.05, n = 3 patients). In contrast, 30 min exposure with empagliflozin did not
      affect CaMKII activity nor Ca2+ -handling but significantly reduced [Na+ ]i .
      CONCLUSIONS: We show for the first time that empagliflozin reduces CaMKII
      activity and CaMKII-dependent SR Ca2+ leak. Reduced Ca2+ leak and improved Ca2+
      transients may contribute to the beneficial effects of empagliflozin in HF.

PMID- 30117723
TI  - Evaluation of end-tidal carbon dioxide as a predictor of return of spontaneous
      circulation in dogs and cats undergoing cardiopulmonary resuscitation.
AB  - OBJECTIVE: To determine whether the partial pressure of end-tidal carbon dioxide
      (PetCO2 ) could predict return of spontaneous circulation (ROSC) in patients with
      cardiopulmonary arrest (CPA) undergoing CPR. DESIGN: Prospective observational
      study. SETTING: Two private specialty referral hospitals. ANIMALS: Thirty-five
      client-owned dogs and cats in CPA in which CPR was performed and pertinent data
      recorded on a purpose-made form. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: PetCO2 was recorded at 1-minute intervals during CPR. Hospital, animal,
      arrest, and outcome variables were also reported in the Utstein style where
      possible. Twelve animals (7 dogs and 5 cats) achieved ROSC; 4 of these (2 dogs
      and 2 cats) had sustained ROSC, of which 1 dog was discharged alive. Patients
      that achieved ROSC had significantly higher initial PetCO2 (P = 0.0083), peak
      PetCO2 (P < 0.0001), average PetCO2 (P < 0.0001), and DeltaPetCO2 (difference
      between last and first recorded PetCO2 ; P = 0.0004) than patients not
      resuscitated. The PetCO2 accurately discriminated between ROSC and failure to
      achieve ROSC at minutes 3, 4, 5, 6, 7, and 8 of CPR with area under the receiver
      operating characteristic curve of 0.926, 0.967, 0.938, 0.933, 0.956, and 1.00,
      respectively. The optimal cutoff PetCO2 was 18 mm Hg (2.4 kPa), with a
      sensitivity of >=80% and a specificity of >=95% at minutes 3, 4, 5, 6, and 8,
      correctly classifying 91-100% of cases. CONCLUSIONS: The results of this small
      study support previous recommendations to monitor PetCO2 during CPR and suggest
      that PetCO2 during CPR may be useful for determining the probability of ROSC.
      Absolute values and trends of PetCO2 may assist clinicians and owners in making
      decisions for pets with CPA.

PMID- 30117725
TI  - Enabling Effective Electrocatalytic N2 Conversion to NH3 by the TiO2 Nanosheets
      Array under Ambient Conditions.
AB  - NH3 serves as an attractive hydrogen storage medium and a renewable energy sector
      for a sustainable future. Electrochemical reduction is a feasible ambient
      reaction to convert N2 to NH3, while it needs efficient electrocatalysts for the
      N2 reduction reaction (NRR) to meet the challenge associated with N2 activation.
      In this Letter, we report on our recent experimental finding that the TiO2
      nanosheets array on the Ti plate (TiO2/Ti) is effective for electrochemical N2
      conversion to NH3 at ambient conditions. When tested in 0.1 M Na2SO4, such
      TiO2/Ti attains a high NH3 yield of 9.16 * 10-11 mol s-1.cm-2 with corresponding
      Faradaic efficiency of 2.50% at -0.7 V vs reversible hydrogen electrode,
      outperforming most reported aqueous-based NRR electrocatalysts. It also shows
      excellent selectivity for NH3 formation with high electrochemical stability. The
      superior NRR activity is due to the enhanced adsorption and activation of N2 by
      oxygen vacancies in situ generated during electrochemical tests.

PMID- 30117724
TI  - Telocytes are the physiological counterpart of inflammatory fibroid polyps and
      PDGFRA-mutant GISTs.
AB  - PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour
      (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been
      identified as a physiological counterpart of the latter, while interstitial Cajal
      cells (ICC) are considered the precursor of the former. However, ICC hyperplasia
      (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been
      identified in germline KIT-mutant settings but not in PDGFRA-mutant ones,
      challenging the precursor role of ICC for PDGFRA-driven GISTs. Telocytes are a
      recently described interstitial cell type, CD34+/PDGFRA+. Formerly considered
      fibroblasts, they are found in many organs, including the GI tract where they are
      thought to be involved in neurotransmission. Alongside IFPs and gastric GISTs, GI
      wall "fibrosis" has been reported in germline PDGFRA-mutants. Taking the
      opportunity offered by its presence in a germline PDGFRA-mutant individual, we
      demonstrate that this lesion is sustained by hyperplastic telocytes, constituting
      the PDGFRA-mutant counterpart of germline KIT mutation-associated ICCH. Moreover,
      our findings support a pathogenetic relationship between telocyte hyperplasia and
      both IFPs and PDGFRA-mutant GISTs. We propose the term "telocytoma" for defining
      IFP, as it conveys both the pathogenetic (neoplastic) and histotypic
      ("telocytary") essence of this tumour, unlike IFP, which rather evokes an
      inflammatory-hyperplastic lesion.

PMID- 30117726
TI  - Highly Efficient Charge Collection in Bulk-Heterojunction Organic Solar Cells by
      Anomalous Hole Transfer and Improved Interfacial Contact.
AB  - The dilute donor-fullerene bulk heterojunction (BHJ) has been proven to be an
      efficient architecture of organic solar cells. However, the hole-extraction
      pathway and the origin of the high open-circuit voltage ( VOC) in this peculiar
      architecture remains elusive. Direct evidence is provided here that the
      photogenerated holes can be extracted via the acceptor phase even under the
      operating conditions. Meanwhile VOC is found to be closely correlated with the
      surface composition at the MoO3/BHJ interface. Extending these findings into
      device optimization, more than 37% enhancement is achieved in a prototype BHJ
      device. These results evoke renewed insight into the underlying physics in
      organic solar cells.

PMID- 30117727
TI  - Ultralong 1D Vacancy Channels for Rapid Atomic Migration during 2D Void Formation
      in Monolayer MoS2.
AB  - High-energy irradiation of materials can lead to void formation due to the
      aggregation of vacancies, reducing the local stress in the system. Studying void
      formation and its interplay with vacancy clusters in bulk materials at the atomic
      level has been challenging due to the thick volume of 3D materials, which
      generally limits high-resolution transmission electron microscopy. The thin
      nature of 2D materials is ideal for studying fundamental material defects such as
      dislocations and crack tips and has potential to reveal void formation by vacancy
      aggregation in detail. Here, using atomic-resolution in situ transmission
      electron microscopy of 2D monolayer MoS2, we capture rapid thermal diffusion of S
      vacancies into ultralong (~60 nm) 1D S vacancy channels that initiate void
      formation at high vacancy densities. Strong interactions are observed between the
      1D channels and void growth, whereby Mo and S atoms are funneled back and forth
      between the void edge and the crystal surface to enable void enlargement.
      Preferential void growth up to 100 nm is shown to occur by rapid digestion of 1D
      S vacancy channels as they make contact. These results reveal the atomistic
      mechanisms behind void enlargement in 2D materials under intense high-energy
      irradiation at high temperatures and the existence of ultralong 1D vacancy
      channels. This knowledge may also help improve the understanding of void
      formation in other systems such as nuclear materials, where direct visualization
      is challenging due to 3D bulk volume.

PMID- 30117728
TI  - Targeted Structure-Activity Analysis of Endochin-like Quinolones Reveals Potent
      Qi and Qo Site Inhibitors of Toxoplasma gondii and Plasmodium falciparum
      Cytochrome bc1 and Identifies ELQ-400 as a Remarkably Effective Compound against
      Acute Experimental Toxoplasmosis.
AB  - Cytochrome bc1 inhibitors have been broadly studied as human and veterinary
      medicines and agricultural fungicides. For the most part, cytochrome bc1
      inhibitors compete with ubiquinol at the ubiquinol oxidation (Qo) site or with
      ubiquinone at the quinone reduction (Qi) site. 4(1 H)-Quinolones with 3-position
      substituents may inhibit either site based on quinolone ring substituents. 4(1 H)
      Quinolones that inhibit the Qi site are highly effective against toxoplasmosis,
      malaria, and babesiosis and do not inhibit human cytochrome bc1. We tested a
      series of 4(1 H)-Quinolones against wild-type and drug resistant strains of
      Toxoplasma gondii and Plasmodium falciparum. These experiments identified very
      potent compounds that inhibit T. gondii proliferation at picomolar
      concentrations. The most potent compounds target the Qo site, and for these
      compounds, an alkyl side chain confers potency against T. gondii greater than
      that of bulkier side chains. Our experiments also show that substituents on the
      quinolone ring influenced selectivity between T. gondii and P. falciparum and
      between Qo and Qi site-mediated activity. Comparison of the parasite cytochrome b
      sequences identified amino acids that are associated with drug resistance in P.
      falciparum that exist naturally in wild-type T. gondii. These underlying
      differences may influence drug susceptibility. Finally, a Qo site active 4(1 H)
      quinolone-3-diarylether tested in a murine model of toxoplasmosis was superior to
      atovaquone, resulting in survival from Type I strain T. gondii infection. These
      experiments identify highly effective compounds for toxoplasmosis and provide
      valuable insight into the structure-activity relationship of cytochrome bc1
      inhibitors.

PMID- 30117729
TI  - Resident Microglia Activate before Peripheral Monocyte Infiltration and p75NTR
      Blockade Reduces Microglial Activation and Early Brain Injury after Subarachnoid
      Hemorrhage.
AB  - Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (SAH)
      contributes to high morbidity and mortality. Although it is well recognized that
      acute neuroinflammation reaction is one of the most important triggers of EBI,
      pharmacotherapy proved to be clinically effective against the initiating of
      neuroinflammation after SAH is lacking. The resident microglia and infiltrated
      peripheral monocyte are two main types of immune cells in central nervous system
      (CNS) and control the inflammation process in brain after SAH. But the time
      course and relative contributions of these two immune cell activations after SAH
      are unknown. The p75 neurotrophin receptor (p75NTR), member of TNF receptor
      superfamily, expresses on infiltrated peripheral monocytes and suppresses their
      proinflammatory action after brain insults. But the p75NTR expression on resident
      microglia in vivo is rarely explored and their function keeps elusive. Therefore,
      we designed this study to investigate the time course of resident microglia
      activation and peripheral monocyte infiltration, as well as the microglial
      expression of p75NTR by using CX3C-chemokine receptor 1 (Cx3cr1) and chemokine
      receptor 2 (Ccr2) double transgenic mice (Cx3cr1GFP/+Ccr2RFP/+) after SAH. The
      results showed activated microglia was observed in cortex as early as 24 h and
      further increased at 48 and 72 h post SAH, while the infiltrated monocyte was not
      found until 72h. In addition, activated microglia expressed p75NTR acutely and
      p75NTR specific antagonist TAT-Pep5 significantly reduced microglia activation,
      neuroinflammation and EBI from 24 to 72 h. Together, these data suggest that the
      early neuroinflammation reaction might be initiated and intensified mainly by
      resident microglia rather than infiltrated monocyte at least in the first 48 h
      after SAH and p75NTR blockading by TAT-Pep5P might alleviate EBI through
      mediating microglial activation.

PMID- 30117730
TI  - Blocking Polysulfides and Facilitating Lithium-Ion Transport: Polystyrene
      Sulfonate@HKUST-1 Membrane for Lithium-Sulfur Batteries.
AB  - Minimizing the shuttle effect of polysulfides (PS) is crucial for practical
      applications of lithium-sulfur (Li-S) batteries. However, the trade-off between
      effective suppression of the shuttle effect and fast redox reaction kinetics is
      inevitable for separator-based Li-S batteries. Herein, via a self-confined solid
      conversion process, we develop a polystyrene sulfonate (PSS)-threaded well
      intergrown HKUST-1 (Cu3(BTC)2) (BTC: 1,3,5-benzenetricarboxylic acid)-coated
      Celgard separator (PSS@HKUST-1/Celgard, PHC) for high-performance Li-S batteries.
      The PHC membrane favors the interception and accommodation of long-chain PS.
      Notably, enormous sulfonate groups of the three-dimensional PSS networks in
      PSS@HKUST-1 membrane significantly facilitate lithium-ion transport, which
      guarantee fast redox kinetics. The PHC separator demonstrates efficient
      inhibition of PS (i.e., 4 orders of magnitude lower in PS permeation rate) with
      fast Li+ transportation (i.e., 71% higher in ionic conductivity) than the Celgard
      separator. When applying the PHC membrane in Li-S batteries with conventional
      sulfur/super P carbon cathode, highly reversible capacity with an average fading
      rate of 0.05% per cycle is maintained for 500 cycles at 0.5 C, excellent rate
      performance up to 5 C, and high areal capacity over 7 mA h cm-2 are also
      achieved. This work paves a new way for addressing the trade-off between
      suppressing the PS shuttle effect and fast kinetic reaction for separator-based
      Li-S batteries.

PMID- 30117731
TI  - Impact of Mitochondrion-Targeting Group on the Reactivity and Cytostatic Pathway
      of Platinum(IV) Complexes.
AB  - Platinum(IV) complexes are prodrugs of cisplatin with multiple potential
      advantages over platinum(II) drugs. Mitochondria play pivotal roles in producing
      energy and inducing death of cancer cells. Two platinum(IV) complexes, namely,
      c,c,t-[Pt(NH3)2Cl2(OH)(OCOCH2CH2CH2CH2PPh3)]Br and c,c,t
      [Pt(NH3)2Cl2(OCOCH2CH2CH2CH2PPh3)2]Br2, were designed to explore the effect of
      mitochondrion-targeting group(s) on the bioactivity and cytotoxicity of
      platinum(IV) complexes. The complexes were characterized by electrospray
      ionization mass spectrometry, reverse-phase high-performance liquid
      chromatography, and multinuclear (1H, 13C, 31P, and 195Pt) NMR spectroscopy. The
      introduction of triphenylphosphonium targeting group(s) markedly influences the
      reactivity and cytotoxicity of the Pt(IV) complexes. The targeted complex
      displays more potent disruptive effect on mitochondria but less inhibitory effect
      on cancer cells than cisplatin. The lipophilicity of the Pt(IV) complexes is
      enhanced by the targeting group(s), while their reactivity to DNA is decreased.
      As a result, the mitochondrial morphology and adenosine triphosphate producing
      ability are impaired, which constitutes an alternative pathway to inhibit cancer
      cells. This study shows that both the reactivity of platinum(IV) center and the
      property of axial targeting ligand exert influences on the cytotoxicity of
      targeted Pt(IV) complexes. For targeting groups with pharmacological activities,
      their intrinsic function could enrich the anticancer mechanism of Pt(IV)
      complexes.

PMID- 30117732
TI  - Instantaneous Detection of Trichlorinated Carbon via Photo-Induced Electron
      Transfer toward Chemosensor for Toxic Organochlorides.
AB  - Despite the usefulness of organochlorides as raw materials for organic synthesis,
      they cause several issues in the human body, such as hepatic dysfunction, tumor,
      and heavy damage to the central nervous system. Especially when organochlorides
      contain three or more chlorinated carbons, they tend to be more toxic to the
      human body possibly owing to relatively high reactivity. Several electron donors
      (TPCAs) are designed to devise a novel detection system for toxic organochlorides
      containing trichlorinated carbons, and the detection mechanism of the devised
      sensor system is systematically identified by EPR measurement and the analysis of
      the solution after the detection of chloroform, which is used as a model
      compound. Since the detection system simultaneously utilizes the radical
      generation capability and the low LUMO level of the trichlorinated carbon, it
      provides high selectivity against most of the common organic compounds including
      other organochlorides containing mono- or dichlorinated carbons, and the
      outstanding selectivity of the designed sensor has been verified with Mirex
      composed of numerous chlorinated carbons. In addition, the detection system
      exhibits immediate sensing capability because only electron transfer and radical
      reaction are involved in the detection process. Finally, when diphosgene is
      detected with the devised sensing platform, a noticeable change in fluorescence
      intensities can be identified within 5 s even for a diphosgene concentration of
      less than 1 ppm.

PMID- 30117733
TI  - Hierarchical Design of NiOOH@Amorphous Ni-P Bilayer on a 3D Mesh Substrate for
      High-Efficiency Oxygen Evolution Reaction.
AB  - Recently, 3d metal phosphide and metal-phosphorus alloy have been intensively
      studied for the oxygen evolution reaction (OER). Research work has indicated that
      the presence of phosphorus could lead to the formation of a phosphide/(hydro)
      oxide core/shell structure. In this work, we have developed a fabrication
      technique for a robust NiOOH@amorphous Ni-P bilayer on a zirconia mesh support
      through the collaboration of electroless deposition and robocasting. During the
      electroless deposition, a fully amorphous structure can be obtained with a
      certain phosphorus content (7-8 wt %). Relatively thick films (in the order of 5
      MUm) had an excellent adhesion on the mesh structure because of the large
      curvature. A stable Ni oxy/hydroxide surface (~200 nm) can be formed in bilayer
      nature (NiOOH/Ni-P) due to preactivation. The combination of catalyst active
      sites on the surface and high conductivity of metallic body enables good OER
      performance with an overpotential of 286 mV at a current density of 10 mA cm-2.
      Together with excellent chemical stability and mechanical strength of the ceramic
      substrate, this novel combination gives rather excellent adhesion and stability
      in alkaline solution and provides a different angle for the hierarchical design
      of corrosion resistant and high-performance OER electrodes for industry.

PMID- 30117734
TI  - Layered g-C3N4@Reduced Graphene Oxide Composites as Anodes with Improved Rate
      Performance for Lithium-Ion Batteries.
AB  - As important anodes in lithium-ion batteries, graphene is always faced with the
      aggregation problem that makes most of the active sites lose their function at
      high current densities, resulting in low Li-ion intercalation capacity and poor
      rate performance. To address this issue, a layered g-C3N4@reduced graphene oxide
      composite (g-C3N4@RGO) was prepared via a scalable and easy strategy. The
      resultant g-C3N4@RGO composite possesses large interlayer distances, rich N
      active sites, and a microporous structure, which largely improves Li storage
      performance. It shows excellent cycle stability (899.3 mA h g-1 after 350 cycles
      under 500 mA g-1) and remarkable rate performance (595.1 mA h g-1 after 1000
      cycles under 1000 mA g-1). Moreover, the g-C3N4@RGO electrode exhibits desired
      capacity retention and relatively high initial Coulombic efficiency of 58.8%.
      Impressively, this result is better than that of RGO (29.1%) and most of RGO
      based anode materials reported in the literature. Especially, the g-C3N4@RGO
      based electrode is enough to power two tandem red-light-emitting diodes and run a
      digital watch. Interestingly, the electronic watch can work continuously for more
      than 20 days. This novel strategy shows the great potential of g-C3N4@RGO
      composites as energy-storage materials.

PMID- 30117735
TI  - Obtaining Chemical Selectivity from a Single, Nonselective Sensing Film: Two
      Stage Adaptive Estimation Scheme with Multiparameter Measurement to Quantify
      Mixture Components and Interferents.
AB  - A new approach is reported to detect and quantify the members of a group of small
      aromatic-molecule target analytes: benzene, toluene, ethylbenzene, and xylenes
      (BTEX), dissolved in water, in the presence of interferents, using only the data
      collected from a single polymer-coated SH-SAW (shear horizontal surface acoustic
      wave) device and a two-stage adaptive estimation scheme. This technique is
      composed of exponentially weighted recursive least-squares estimation (EW-RLSE)
      and a bank of Kalman filters (BKFs) and does not require any prior knowledge of
      the initial concentration range of the target analytes. The proposed approach
      utilizes the transient sensor response to sorption and/or desorption of the
      analytes as well as the error range associated with the response time constants
      to provide more information about the analyte-specific interactions with the
      polymer film. The approach assumes that the sensor response to contaminated
      groundwater is a linear combination of the responses to the single target
      analytes, the interferents that interact with the selected polymer sensor
      coatings, and measurement noise. The proposed technique was tested using actual
      sensor responses to contaminated groundwater samples containing multiple BTEX
      compounds with concentrations ranging from 10 to 2000 parts per billion, as well
      as common interferents including ethanol, 1,2,4-trimethylbenzene, naphthalene, n
      heptane, and MTBE (methyl tert-butyl ether). Estimated concentration values,
      accurate to +/-10% for benzene/toluene and +/-15% for ethylbenzene/xylenes, are
      obtained in near-real time. The utilization of sorption and/or desorption data
      enables detection and quantification of BTEX compounds with improved accuracy,
      high tolerance to measurement noise, and improved chemical selectivity.

PMID- 30117736
TI  - Dense and Dynamic Polyethylene Glycol Shells Cloak Nanoparticles from Uptake by
      Liver Endothelial Cells for Long Blood Circulation.
AB  - Research into long-circulating nanoparticles has in the past focused on reducing
      their clearance by macrophages. By engineering a hierarchical polyethylene glycol
      (PEG) structure on nanoparticle surfaces, we revealed an alternative mechanism to
      enhance nanoparticle blood circulation. The conjugation of a second PEG layer at
      a density close to but lower than the mushroom-to-brush transition regime on
      conventional PEGylated nanoparticles dramatically prolongs their blood
      circulation via reduced nanoparticle uptake by non-Kupffer cells in the liver,
      especially liver sinusoidal endothelial cells. Our study also disclosed that the
      dynamic outer PEG layer reduces protein binding affinity to nanoparticles,
      although not the total number of adsorbed proteins. These effects of the outer
      PEG layer diminish in the higher density regime. Therefore, our results suggest
      that the dynamic topographical structure of nanoparticles is an important factor
      in governing their fate in vivo. Taken together, this study advances our
      understanding of nanoparticle blood circulation and provides a facile approach
      for generating long circulating nanoparticles.

PMID- 30117737
TI  - Preparation of Phenanthridines from o-Cyanobiaryls via Addition of Organic
      Lithiums to Nitriles and Imino Radical Cyclization with Iodine.
AB  - Simple treatment of 2-cyanobiaryls with methyllithium, ethylmagnesium bromide,
      butyllithium, phenyllithium, p-methylphenyllithium, etc., followed by the
      reaction with water and then with molecular iodine at 60  degrees C provided
      efficiently 6-methyl-, 6-ethyl-, 6-butyl-, 6-phenyl, 6-( p
      methylphenyl)phenanthridines, etc., in good yields, respectively. Here, imines
      formed through the addition of carbanion onto the nitriles reacted with molecular
      iodine to form N-iodoimines smoothly, and their warming treatment induced the
      formation of imino radicals that smoothly cyclized onto the aryl group to give 6
      alkyl- and 6-arylphenanthridines.

PMID- 30117738
TI  - Potent and Selective Tetrahydroisoquinoline Kappa Opioid Receptor Antagonists of
      Lead Compound (3 R)-7-Hydroxy- N-[(1 S)-2-methyl-1-(piperidin-1-ylmethyl)propyl]
      1,2,3,4-tetrahydroisoquinoline-3-carboxamide (PDTic).
AB  - Past studies have shown that it has been difficult to discover and develop potent
      and selective kappa opioid receptor antagonists, particularly compounds having
      potential for clinical development. In this study, we present a structure
      activity relationship (SAR) study of a recently discovered new class of
      tetrahydroisoquinoline kappa opioid receptor antagonists which led to (3 R)-7
      hydroxy- N-{(1 S)-2-methyl-1-[(-4-methylpiperidine-1-yl)methyl]propyl}-1,2,3,4
      tetrahydroisoquinoline-3-carboxamide (12) (4-Me-PDTic). Compound 12 had a Ke =
      0.37 nM in a [35S]GTPgammaS binding assay and was 645- and >8100-fold selective
      for the kappa relative to the MU and delta opioid receptors, respectively.
      Calculated log BB and CNS (central nervous system) multiparameter optimization
      (MPO) and low molecular weight values all predict that 12 will penetrate the
      brain, and pharmacokinetic studies in rats show that 12 does indeed penetrate the
      brain.

PMID- 30117739
TI  - Proteasome versus Thioredoxin Reductase Competition as Possible Biological
      Targets in Antitumor Mixed Thiolate-Dithiocarbamate Gold(III) Complexes.
AB  - New mixed gold(III) derivatives with dithiocarbamate and thiolate ligands have
      been synthesized and characterized. They display high anticancer activity against
      colon cancer cell lines without affecting to differentiated enterocytes, high
      stability in phosphate-buffered saline solution, and resistance to gold reduction
      in the presence of reducing agents in the majority of the derivatives. Some of
      them show interaction with thioredoxin reductase as derived from in vitro
      analysis and computational studies. However, a competition between this enzyme
      and proteasome is detected in cells, which is corroborated by the determination
      of proteasomal chymotrypsin-like activity inhibition. In addition, some of these
      dithiocarbamate gold(III) derivatives reduce cell viability and proliferation by
      intrinsic apoptotic pathway, with changes in mitochondrial membrane potential,
      cytochrome c release and caspase-3 activation. Consequently, our results show new
      complexes with proteasome as possible target in colorectal cancer.

PMID- 30117740
TI  - Spatial Cross-Correlated Diffusion of Colloids under Shear Flow.
AB  - The spatial cross-correlated diffusion of colloidal particles is often used as an
      essential tool to study the dynamic properties of a fluid because it directly
      describes the hydrodynamic interaction between two particles in a fluid. However,
      the experimental measurement of cross-correlated diffusion can be substantially
      modified by even a weak shear flow. In this work, the effect of a shear flow on
      spatial cross-correlated diffusion is demonstrated using experimental
      measurements that show a clear dependence on pair angles. An analytical solution
      is proposed to explain the experimental observations. A numerical simulation is
      performed to systemically demonstrate the influence of shear flow on spatial
      cross-correlated diffusion. The results of the experiment, theoretical analysis,
      and numerical simulation agree well with each other. Therefore, this research
      provides a sensitive experimental method to determine the weak shear flow in any
      quasi-two-dimensional fluid systems.

PMID- 30117741
TI  - Role of Mg2+ Ions in DNA Hydrolysis by EcoRV, Studied by the 3D-Reference
      Interaction Site Model and Molecular Dynamics.
AB  - The role of Mg2+ ions during precursor formation in DNA hydrolysis by the
      homodimeric restriction enzyme EcoRV was elucidated based on the 3D-reference
      interaction site model (RISM) theory and the molecular dynamics (MD) simulation.
      From an analysis of the spatial distribution of Mg2+ in an active site using 3D
      RISM, we identified a new position for Mg2+ in the X-ray EcoRV-DNA complex
      structure ( 1rvb ). We refer to the position as site IV?. Site IV? is almost at
      the same position as that of a Ca2+ ion in the superimposed X-ray
      crystallographic active-site structure of the PvuII-DNA complex ( 1f0o ). 3D-RISM
      was also used to locate the position of water molecules, including the water
      nucleophile at the active site. MD simulations were carried out with the initial
      structure having two Mg2+ ions at site IV? and at site I*, experimentally
      identified by Horton et al., to find a stable complex structure in which the DNA
      fragment was rearranged to orient the scissile bond direction toward the water
      nucleophile. The equilibrium active-site structure of the EcoRV-DNA complex
      obtained from the MD simulation was similar to the superimposed X-ray
      crystallographic structure of the BamHI-DNA complex ( 2bam ). In the active-site
      structure, two metal ions have almost the same position (<=1.0 A) as that of 2bam
      , and the scissile phosphate is twisted to orient the scissile bond toward the
      water nucleophile, as is the case in 2bam . We propose the equilibrium active
      site structure obtained in this study as a precursor for the hydrolysis reaction
      of EcoRV.

PMID- 30117742
TI  - A Workflow to Improve Variant Calling Accuracy in Molecular Barcoded Sequencing
      Reads.
AB  - Multiplexed molecular barcoded amplicon sequencing has been previously
      demonstrated to improve the sensitivity of low-frequency variant detection.
      Molecular barcoded reads can be used to identify and correct amplification biases
      introduced during library preparation and sequencing errors. We propose a generic
      workflow to improve variant calling accuracy that takes advantage of molecular
      barcoded sequencing reads by applying a base score correction method to duplicate
      or overlapping read pairs across the targeted panel. The workflow is able to
      reduce the false-positive rate of variant calls in homopolymer and repetitive
      regions where the sequencer commonly encounters phasing errors interfering with
      base calling. The analysis was focused on three specific regions within a custom
      QIAseq targeted DNA (Qiagen, USA) of 220 genes observed to have a high false
      positive rate in a clinical validation study. Uncorrected and corrected datasets
      were compared at targeted regions to reference calls from NIST and exome data
      from a reference laboratory (Macrogen, USA). Base correction removed all false
      positives identified without the correction method and retained the true positive
      call in the dataset. We have shown that our workflow incorporating base
      correction of molecular barcoded sequencing data can be applied to germline
      sequencing to improve variant calling accuracy in genomic regions with certain
      repetitive sequence motifs.

PMID- 30117743
TI  - Effect of High Pressure Processing on a Wide Variety of Human Noroviruses
      Naturally Present in Aqua-Cultured Japanese Oysters.
AB  - The contamination of oysters with human norovirus (HuNoV) poses a human health
      risk, as oysters are often consumed raw. In this study, the effect of high
      pressure processing (HPP) on a wide variety of HuNoVs naturally present in aqua
      cultured Japanese oysters was determined through a polymerase chain reaction
      based method with enzymatic pretreatment, to distinguish between infectious
      HuNoV. Among five batches, genogroup I. genotype 1 (GI.1), GI.2, GI.3, and GI.8
      HuNoV were detected from only one oyster not treated with HPP in the fifth batch,
      while genogroup II. genotype 1 to 4 (GII.1 to 4), GII.6, GII.8., GII.9, GII.13,
      GII.16, GII.17, and GII.22 HuNoV were detected from oysters not treated with HPP
      in all tested batches as determined by next-generation sequencing analysis.
      Neither GI nor GII HuNoV was detected in the oysters of any of the batches after
      HPP treatment. To our knowledge, this is the first study to investigate the
      effect of HPP on a wide variety of HuNoVs naturally present in aqua-cultured
      oysters.

PMID- 30117745
TI  - Clinical impact of mineralocorticoid receptor antagonists treatment after acute
      coronary syndrome in the real world: A propensity score matching analysis.
AB  - BACKGROUND: Recent studies suggest that the benefit of mineralocorticoid receptor
      antagonists in the acute coronary syndrome setting is controversial. The aim of
      this study was to examine the current long-term prognostic benefit of
      mineralocorticoid receptor antagonists in patients with acute coronary syndrome.
      MATERIAL AND METHODS: We conducted a retrospective cohort study of 8318
      consecutive acute coronary syndrome patients. Baseline patient characteristics
      were examined and a follow-up period was established for registry of death, major
      cardiovascular adverse events and heart failure re-hospitalization. We performed
      a propensity-matching analysis to draw up two groups of patients paired according
      to whether or not they had been treated with mineralocorticoid receptor
      antagonists. The prognostic value of mineralocorticoid receptor antagonists to
      predict events during follow-up was analysed using Cox regression. RESULTS: Among
      the study participants, only 524 patients (6.3%) were discharged on
      mineralocorticoid receptor antagonists. Patients on mineralocorticoid receptor
      antagonists had a different clinical and pharmacological profile. These
      differences disappeared after the propensity score analysis. The median follow-up
      was 40.7 months. After the propensity score analysis, the cardiovascular
      mortality and heart failure readmission rates were similar between patients who
      were discharged on mineralocorticoid receptor antagonists and those whose not.
      The use of mineralocorticoid receptor antagonists was only associated with a
      reduction in major cardiovascular adverse events (hazard ratio=0.83, 95%
      confidence interval 0.69-0.97, p=0.001). CONCLUSIONS: Our results do not
      corroborate the long-term benefit of mineralocorticoid receptor antagonists to
      improve survival after acute coronary syndrome in a large cohort of patients with
      heart failure or reduced left ventricular ejection fraction and diabetes. Their
      prescription was associated with a significantly lower incidence of major
      cardiovascular adverse events during the long-term follow-up without effect on
      heart failure development.

PMID- 30117744
TI  - Heterologous effects of infant BCG vaccination: potential mechanisms of immunity.
AB  - The current antituberculosis vaccine, BCG, was derived in the 1920s, yet the
      mechanisms of BCG-induced protective immunity and the variability of protective
      efficacy among populations are still not fully understood. BCG challenges the
      concept of vaccine specificity, as there is evidence that BCG may protect
      immunized infants from pathogens other than Mycobacterium tuberculosis -
      resulting in heterologous or nonspecific protection. This review summarizes the
      up-to-date evidence for this phenomenon, potential immunological mechanisms and
      implications for improved childhood vaccine design. BCG induces functional
      changes in infant innate and adaptive immune compartments, encouraging their
      collaboration in the first year of life. Understanding biological mechanisms
      beyond heterologous BCG effects is crucial to improve infant protection from
      infectious diseases.

PMID- 30117746
TI  - Two-Exponential Models of Gene Expression Patterns for Noisy Experimental Data.
AB  - Spatial pattern formation of the primary anterior-posterior morphogenetic
      gradient of the transcription factor Bicoid (Bcd) has been studied experimentally
      and computationally for many years. Bcd specifies positional information for the
      downstream segmentation genes, affecting the fly body plan. More recently, a
      number of researchers have focused on the patterning dynamics of the underlying
      bcd messenger RNA (mRNA) gradient, which is translated into Bcd protein. New,
      more accurate techniques for visualizing bcd mRNA need to be combined with
      quantitative signal extraction techniques to reconstruct the bcd mRNA
      distribution. Here, we present a robust technique for quantifying gradients with
      a two-exponential model. This approach (1) has natural, biologically relevant
      parameters and (2) is invariant to linear transformations of the data arising due
      to variation in experimental conditions (e.g., microscope settings, nonspecific
      background signal). This allows us to quantify bcd mRNA gradient variability from
      embryo to embryo (important for studying the robustness of developmental
      regulatory networks); sort out atypical gradients; and classify embryos to
      developmental stage by quantitative gradient parameters.

PMID- 30117747
TI  - Joker de Bruijn: Covering k-Mers Using Joker Characters.
AB  - Sequence libraries that cover all k-mers enable universal and unbiased
      measurements of nucleotide and peptide binding. The shortest sequence to cover
      all k-mers is a de Bruijn sequence of length [Formula: see text]. Researchers
      would like to increase k to measure interactions at greater detail, but face a
      challenging problem: the number of k-mers grows exponentially in k, while the
      space on the experimental device is limited. In this study, we introduce a novel
      advance to shrink k-mer library sizes by using joker characters, which represent
      all characters in the alphabet. Theoretically, the use of joker characters can
      reduce the library size tremendously, but it should be limited as the introduced
      degeneracy lowers the statistical robustness of measurements. In this work, we
      consider the problem of generating a minimum-length sequence that covers a given
      set of k-mers using joker characters. The number and positions of the joker
      characters are provided as input. We first prove that the problem is NP-hard. We
      then present the first solution to the problem, which is based on two algorithmic
      innovations: (1) a greedy heuristic and (2) an integer linear programming (ILP)
      formulation. We first run the heuristic to find a good feasible solution, and
      then run an ILP solver to improve it. We ran our algorithm on DNA and amino acid
      alphabets to cover all k-mers for different values of k and k-mer multiplicity.
      Results demonstrate that it produces sequences that are very close to the
      theoretical lower bound.

PMID- 30117748
TI  - From Laparoscopic Right Colectomy with Extracorporeal Anastomosis to Robot
      Assisted Intracorporeal Anastomosis to Totally Robotic Right Colectomy for
      Cancer: The Evolution of Robotic Multiquadrant Abdominal Surgery.
AB  - BACKGROUND: Intracorporeal anastomosis (IA) in right colectomies shows many
      advantages over extracorporeal anastomosis (EA). Many difficulties encountered in
      laparoscopic IA can be overcome with hybrid robot-assisted IA or recently with
      totally robotic procedures. In the literature, few works have been published
      comparing laparoscopic, hybrid, and totally robotic right colectomies. The aim of
      this study is to retrospectively analyze the improvements brought on by the
      evolution of robotic surgery at our specialized center. MATERIALS AND METHODS:
      Two hundred six (hybrid and totally) robotic right colectomies (RRCs) with IA
      were compared with 160 laparoscopic right colectomies (LRCs) with EA. A separate
      analysis carried out by the robotic group compared 30 totally robotic right
      colectomies (TRRCs) with 176 hybrid robot-assisted right colectomies (HRRCs).
      Demographics, pathological features, operative details, and postoperative
      outcomes were retrospectively analyzed from a prospectively maintained database.
      RESULTS: The groups were comparable with respect to demographics and tumor
      staging. When compared with LRC, RRC showed shorter time to first flatus (P <
      .001), stools (P < .001), solid diet (P < .001), and discharge (P < .001). The
      number of lymph nodes harvested was 23.13 +/- 11.2 in RRC versus 20.5 +/- 11.2 in
      LRC (P = .031). Operative time was longer in RRC (253.0 +/- 47 minutes versus
      209.9 +/- 64 minutes; P < .001), but conversion to open (2.4% versus 18.1%; P <
      .001), anastomotic leaks (0.5% versus 5%; P = .012), and bleeding (0.3% versus
      4.4%; P = .024) were significantly less frequent. Subsequent analysis shows no
      significant increase in operative time in TRRC versus HRRC (261.0 +/- 41 minutes
      versus 251.6 +/- 47.6 minutes; P = .310). Even if not statistically significant,
      TRRC showed faster bowel function recovery and tolerance to solid diet.
      CONCLUSIONS: We confirmed the clinical advantages of RRC with IA over LRC with EA
      in postoperative recovery outcomes and complication rate. Furthermore, our
      preliminary analysis in a cohort of 30 TRRC shows promising results.

PMID- 30117749
TI  - Dynamic metabolic changes in human visual cortex in regions with positive and
      negative blood oxygenation level-dependent response.
AB  - Dynamic metabolic changes were investigated by functional magnetic resonance
      spectroscopy (fMRS) during sustained stimulation of human primary visual cortex.
      Two established paradigms, consisting of either a full-field or a small-circle
      flickering checkerboard, were employed to generate wide-spread areas of positive
      or negative blood oxygenation level-dependent (BOLD) responses, respectively.
      Compared to baseline, the glutamate concentration increased by 5.3% ( p = 0.007)
      during activation and decreased by -3.8% ( p = 0.017) during deactivation. These
      changes were positively correlated with the amplitude of the BOLD response ( R =
      0.60, p = 0.002) and probably reflect changes of tricarboxylic acid cycle
      activity. During deactivation, the glucose concentration decreased by -7.9% ( p =
      0.025) presumably suggesting increased consumption or reduced glucose supply.
      Other findings included an increased concentration of glutathione (4.2%, p =
      0.023) during deactivation and a negative correlation of glutathione and BOLD
      signal changes ( R = -0.49, p = 0.012) as well as positive correlations of
      aspartate ( R = 0.44, p = 0.035) and N-acetylaspartylglutamate ( R = 0.42, p =
      0.035) baseline concentrations with the BOLD response. It remains to be shown in
      future work if the observed effects on glutamate and glucose levels deviate from
      the assumption of a direct link between glucose utilization and regulation of
      blood flow or support previous suggestions that the hemodynamic response is
      mainly driven by feedforward release of vasoactive messengers.

PMID- 30117750
TI  - Decision-making for adrenocortical carcinoma: surgical, systemic, and endocrine
      management options.
AB  - INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare tumor characterized by
      poor prognosis in most cases. Moreover, in most cases ACC produces an excess of
      adrenal steroid hormones with relevant clinical consequences. Areas covered:
      After an extensive literature search, this narrative review addresses diagnostic
      management, including hormonal, radiological and pathological assessment, and
      treatment, which should be directed toward both cancer and hormone related
      problems. While surgery is the first option in ACC without evidence of metastatic
      disease, and the only possibility of cure, the therapeutic management of
      metastatic patients is centered on systemic therapy including mitotane alone or
      in combination with chemotherapy. Mitotane is also used in the adjuvant setting,
      because up to 80% of patients with nonmetastatic ACC show locoregional or distant
      metastases after an apparent complete surgical excision. Expert commentary:
      Management of ACC patients is fraught with many difficulties and should be
      limited to experienced physicians. Each step of clinical management, such as
      diagnosis, prognostication, treatment (both surgical and medical) is challenging
      and carries the possibility of severe mistakes. For this reason, each step of the
      management strategy should be decided in the setting of a multidisciplinary team
      including different expertise (endocrinology, radiology, pathology, oncology), in
      expert centers.

PMID- 30117751
TI  - In the transition from fibrinolysis to primary PCI, the HERO trials help refine
      STEMI ECG interpretation and Q wave analysis potentially alters future
      management.
AB  - Electrocardiogram sub-studies from the Hirulog Early Reperfusion/Occlusion 1 and
      2 trials, which tested bivalirudin as an adjunctive anticoagulant to fibrinolysis
      in ST-elevation myocardial infarction, have contributed to the literature. The
      concept of using the presence of infarct lead Q waves to determine reperfusion
      benefit has subsequently been explored in multiple primary percutaneous coronary
      intervention studies. The angiographic findings before percutaneous coronary
      intervention combine with the baseline electrocardiogram to accurately diagnose
      ST-elevation myocardial infarction and evaluate its potential territory. This
      review discusses the relative merits of the presence of infarct lead Q waves
      versus time duration from symptom onset using observational data from cohorts of
      patients from multiple clinical trials. The presence of infarct lead Q waves at
      presentation has been repeatedly shown to be superior to time duration from
      symptom onset in determining prognosis, despite that continuous variable (time
      duration) statistically should be more powerful than dichotomous variable (Q
      wave). If quantitative or semi-quantitative measurement of Q waves correlates
      well with irreversible myocardial injury in vivo (a research goal of many cardiac
      magnetic resonance imaging studies), Q waves measurements by mirroring ST
      elevation myocardial infarction evolution better than the current metric of time
      duration of symptoms will impact future ST-elevation myocardial infarction
      reperfusion management. Newer methodology will more quickly capture and transmit
      electrocardiogram information including infarct lead Q waves potentially before
      first medical contact, and help differentiate new evolving Q waves of the ongoing
      ST-elevation myocardial infarction from old changes. Q waves as the new metric in
      ST-elevation myocardial infarction reperfusion should be tested in upcoming
      trials.

PMID- 30117752
TI  - Reduction of spike generation frequency by cooling in brain slices from rats and
      from patients with epilepsy.
AB  - This study aimed to understand the mechanism by which brain cooling terminates
      epileptic discharge. Cortical slices were prepared from rat brains (n = 19) and
      samples from patients with intractable epilepsy that had undergone temporal
      lobectomy (n = 7). We performed whole cell current clamp recordings at
      approximately physiological brain temperature (35C) and at cooler temperatures
      (25C and 15C). The firing threshold in human neurons was lower at 25C (-32.6 mV)
      than at 35C (-27.0 mV). The resting potential and spike frequency were similar at
      25C and 35C. Cooling from 25C to 15C did not change the firing threshold, but the
      resting potential increased from -65.5 to -54.0 mV and the waveform broadened
      from 1.85 to 6.55 ms, due to delayed repolarization. These changes enhanced the
      initial spike appearance and reduced spike frequency; moreover, spike frequency
      was insensitive to increased levels of current injections. Similar results were
      obtained in rat brain studies. We concluded that the reduction in spike frequency
      at 15C, due to delayed repolarization, might be a key mechanism by which brain
      cooling terminates epileptic discharge. On the other hand, spike frequency was
      not influenced by the reduced firing threshold or the elevated resting potential
      caused by cooling.

PMID- 30117753
TI  - A Simple Approach to the Reconstruction of a Set of Points from the Multiset of
      Pairwise Distances in n2 Steps for the Sequencing Problem: III. Noise Inputs for
      the Beltway Case.
AB  - The approach based on the removal of redundancy in inputs when reconstructing a
      set of points X from the set of their pairwise distances [Formula: see text] is
      generalized for the beltway case by using integral transformations. It is shown
      that the generalized approach can be successfully used not only for complete and
      error-free sets of pairwise distances [Formula: see text], but also for sets
      [Formula: see text] containing a large number of noise and missing data [Formula:
      see text]. The proposed approach allows to reconstruct X in n2 steps, where n is
      the cardinality of noise input sets.

PMID- 30117754
TI  - Unmet needs in pediatric NAFLD research: what do we need to prioritize for the
      future?
AB  - INTRODUCTION: Pediatric nonalcoholic fatty liver disease (NAFLD) is common
      disorder that has complex pathophysiology and unquantified clinical significance.
      Though there have been major advances in the field, there is much yet to be
      understood. Areas covered: PubMed/MEDLINE and Embase were searched for articles
      related to pediatric NAFLD and nonalcoholic steatohepatitis (NASH) between
      January 1998 and January 2018. The areas considered to be 'unmet needs' were the
      relationship between the intestinal microbiome and perinatal events, clinical
      event risk stratification, and mechanisms underlying portal inflammation. Expert
      commentary: In utero and ex utero factors have been associated with NAFLD and
      also with the intestinal microbiome, but it is not yet known how intestinal
      dysbiosis can be reversed and whether intervention in high-risk neonates could
      alter their propensity for the metabolic syndrome. Children with NAFLD are at
      increased risk of cardiovascular, diabetic, and hepatic diseases, but it is
      unclear how best to stratify children into appropriate risk groups for targeted
      interventions. Finally, the immune processes underlying pediatric NASH are
      thought to differ to those in adult NASH, yet the events surrounding activation
      of periportal lymphocytes are poorly understood. Deepening our understanding of
      these topics may lead to novel therapeutic targets.

PMID- 30117755
TI  - Evaluation of Efficacy and Safety of Dexamethasone Intravitreal Implants of
      Vitrectomized and Nonvitrectomized Eyes in a Real-World Study.
AB  - PURPOSE: To compare the efficacy and safety of the dexamethasone (DEX)
      intravitreal implant of vitrectomized and nonvitrectomized eyes in real-world
      conditions. METHODS: This was a retrospective, multicenter, observational study.
      All consecutive patients presenting with at least one 0.7-mg intravitreal
      injection of DEX implant were included in this study. A total of 186 eyes in 170
      patients were analyzed. Fifty-nine eyes were vitrectomized at baseline and 127
      eyes had no vitrectomy at the last visit. Among the baseline-vitrectomized eyes
      analyzed, 72.9% were treatment naive eyes, and 44.1% of nonvitrectomized eyes had
      no prior treatment. RESULTS: There was no statistically significant difference in
      the variation in best-corrected visual acuity (BCVA) between the 2 groups (P =
      0.343). Variations of BCVA and central macular thickness were not significantly
      different between nonvitrectomized eyes and baseline-vitrectomized eyes. The
      intraocular pressure profile was the same in both nonvitrectomized eyes and
      baseline-vitrectomized eyes. The mean interval between injections was 6.9 months
      (2; 27.7) for nonvitrectomized eyes and 5.2 months (4; 22.1) for baseline
      vitrectomized eyes (P = 0.001). The mean number of IVIs was 2 (1; 6) for
      nonvitrectomized eyes and 2.3 (1; 10) for baseline-vitrectomized eyes (P = 0.188)
      during the total follow-up period. CONCLUSION: This large cohort shows that
      vitrectomy does not seem to influence the efficacy and safety profile of
      dexamethasone intravitreal implant for DME.

PMID- 30117756
TI  - Contamination of Cronobacter spp. in Chinese Retail Spices.
AB  - Crononbacter spp. is an opportunistic foodborne pathogen that causes infections
      in neonates, infants, and immunocompromised adults. Although the contamination of
      spices with Cronobacter has been previously reported in some countries, there
      have been no studies on Cronobacter contamination in China. Therefore, this study
      aimed to investigate the prevalence of Cronobacter spp. in Chinese retail spices.
      Fifty-six packaged Chinese spices were collected from different markets, and 32
      of these were found to be contaminated with Cronobacter. Five species were
      identified from the 54 isolates of the 32 positive samples: Cronobacter sakazakii
      (n = 35), Cronobacter muytjensii (n = 8), Cronobacter malonaticus (n = 6),
      Cronobacter turicensis (n = 3), and Cronobacter dublinensis (n = 2). Pulsed-field
      gel electrophoresis demonstrated high genetic diversity, as 53 PFGE profiles were
      revealed for the 54 isolates. Multilocus sequence typing analysis revealed 46
      sequence types, and of these, 26 were newly identified. Most of the isolates were
      sensitive to antibiotics (n = 15), with the exception of cefazolin. This study
      revealed that the contamination of Chinese retail spices by Cronobacter spp.
      poses a potential risk to the consumer.

PMID- 30117757
TI  - Metabolism and disposition of lesinurad, a uric acid reabsorption inhibitor, in
      humans.
AB  - The objectives of this study were to determine the absolute bioavailability of
      lesinurad and to characterized its disposition in humans. The oral
      bioavailability assessment was performed using a clinical design of simultaneous
      dosing of a therapeutic oral dose of lesinurad with an intravenous infusion of
      [14C]lesinurad microdose. The bioavailability of lesinurad was determined to be
      100%. The disposition of lesinurad in humans involves hepatic oxidation and renal
      elimination following administration of oral [14C]lesinurad dose. Metabolism of
      lesinurad occurred post-systemically with low circulating levels of metabolites
      <3% of total radioactivity as 74.2% of total radioactivity was attributed to
      lesinurad. In vitro metabolism studies identified CYP2C9 as the predominant
      isoform, and summation of metabolites indicated that it was responsible for ~50%
      of metabolism.

PMID- 30117758
TI  - Prediction of RNA-protein interactions using conjoint triad feature and chaos
      game representation.
AB  - RNA-protein interactions (RPIs) play a very important role in a wide range of
      post-transcriptional regulations, and identifying whether a given RNA-protein
      pair can form interactions or not is a vital prerequisite for dissecting the
      regulatory mechanisms of functional RNAs. Currently, expensive and time-consuming
      biological assays can only determine a very small portion of all RPIs, which
      calls for computational approaches to help biologists efficiently and correctly
      find candidate RPIs. Here, we integrated a successful computing algorithm,
      conjoint triad feature (CTF), and another method, chaos game representation
      (CGR), for representing RNA-protein pairs and by doing so developed a prediction
      model based on these representations and random forest (RF) classifiers. When
      testing two benchmark datasets, RPI369 and RPI2241, the combined method (CTF+CGR)
      showed some superiority compared with four existing tools. Especially on RPI2241,
      the CTF+CGR method improved prediction accuracy (ACC) from 0.91 (the best record
      of all published works) to 0.95. When independently testing a newly constructed
      dataset, RPI1449, which only contained experimentally validated RPIs released
      between 2014 and 2016, our method still showed some generalization capability
      with an ACC of 0.75. Accordingly, we believe that our hybrid CTF+CGR method will
      be an important tool for predicting RPIs in the future.

PMID- 30117759
TI  - A Qualitative Study Exploring Yoga in Veterans with PTSD Symptoms.
AB  - Quantitative studies of yoga have reported reduced posttraumatic stress disorder
      (PTSD) symptoms in veterans, but little is known about how and why veterans are
      attracted to and stick with a yoga practice. Guided by the Health Belief Model,
      this study examined veterans' perceptions of the benefits, barriers, and
      motivations to continue practicing trauma-sensitive yoga. Interviews were
      conducted with nine individuals, five of whom completed a 6-week trauma-sensitive
      yoga intervention designed for veterans and four who did not complete the
      intervention. Transcripts were analyzed for themes. The benefits identified by
      veterans were finding mental stillness, body awareness, and social connection.
      The barriers were perceptions that yoga is socially unacceptable, especially for
      men, and physically unchallenging. Understanding these benefits and barriers can
      help to make yoga more attractive to service members and veterans. For example,
      medical personnel can refer service members and veterans to yoga not only for
      PTSD symptoms, but also to address back pain and to reduce isolation. Access to
      male yoga instructors, especially those who are themselves service members or
      veterans, could be expanded, and classes could be integrated into physical
      activity routines required of active-duty personnel. Promotional materials can
      feature male service members and veterans with captions related to yoga as a way
      to increase resiliency, self-sufficiency, and physical and mental mission
      readiness. Findings from this study can help the Department of Defense and the
      Veterans Health Administration implement yoga as an adjunct or alternative
      treatment for veterans with PTSD symptoms.

PMID- 30117760
TI  - A Feasibility Study of Restorative Yoga Versus Vigorous Yoga Intervention for
      Sedentary Breast and Ovarian Cancer Survivors.
AB  - Yoga has been shown to improve cancer survivors' quality of life, yet regular
      yoga practice is a challenge for those who are sedentary. We conducted a pilot
      randomized controlled study to assess feasibility and adherence of two types of
      yoga intervention among sedentary cancer survivors. Sedentary breast and ovarian
      cancer survivors were randomized to practice either restorative yoga (minimal
      physical exertion, Group R) or vigorous yoga (considerable physical exertion,
      Group V) in three 60-minute supervised sessions a week for 12 weeks, followed by
      12 weeks of home practice. Accrual, adherence, and attendance rates were
      assessed. Of the 226 eligible patients, 175 (77%) declined to participate in the
      study, citing time commitment and travel as the most common barriers. Forty-two
      subjects consented to participate in the study. Of the 35 participants who began
      the intervention (20 in Group R and 15 in Group V), adherence rate (percentage
      remaining in the study at week 12) was 100% and 87%, respectively. Rate of
      adequate attendance (more than 66% of the scheduled supervised sessions) was 85%
      and 73%, respectively. Rate of completion of the home practice period was 85% and
      77%, respectively. In this study, sedentary cancer survivors were able to adhere
      to a long-term, regular yoga regimen. The rate of adequate attendance was higher
      for restorative yoga. Future studies for sedentary patients should focus on
      reducing time commitment and travel requirements to improve recruitment, and on
      using restorative yoga as a more feasible intervention for this population.

PMID- 30117762
TI  - Introduction: Pow Meng Yap and the culture-bound syndromes.
AB  - PM Yap's most significant intellectual achievement was his development of the
      concept of the culture-bound syndrome, which synthesized years of research into
      transcultural psychiatry, and situated this work within this field by drawing on
      elaborated nosological schema that challenged some of the ethnocentric
      assumptions made by previous psychiatrists who had tried to understand mental
      illnesses that presented in non-western cultures. This introduction to Yap's 1951
      paper emphasizes that Yap needs to be understood as working within the western
      tradition of transcultural psychiatry, and argues that his English training and
      his continual engagement with western psychiatric and philosophical frameworks is
      the best way to conceive of his contributions to this field. Yap's paper,
      republished below as the Classic Text, was his first foray into comparative
      transcultural psychiatry.

PMID- 30117763
TI  - Total improvement after surgery for obstructive sleep apnea syndrome in a patient
      with concurrent malignant idiopathic intracranial hypertension.
AB  - The association between idiopathic intracranial hypertension (IIH) and
      obstructive sleep apnea syndrome (OSAS) constitutes an interesting point of
      discussion regarding clinical approaches as well as the underlying
      pathophysiological mechanisms. Here, the case of a 42-year-old female with
      malignant IIH and OSAS is illustrated. Initially, the patient was treated with
      lumboperitoneal shunt surgery. However, OSAS surgery provided total recovery from
      the recurrent symptoms developing secondary to lumboperitoneal shunt malfunction.
      The authors point out the importance of identifying OSAS as a crucial causative
      agent in some IIH subtypes. Future studies are warranted to clarify this
      underestimated association.

PMID- 30117761
TI  - Mixed Meal and Intravenous L-Arginine Tests Both Stimulate Incretin Release
      Across Glucose Tolerance in Man: Lack of Correlation with beta Cell Function.
AB  - BACKGROUND: The aims of this study were to 1. define the responses of glucagon
      like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP),
      glucagon, and peptide YY (PYY) to an oral meal and to intravenous L-arginine; and
      2. examine correlation of enteroendocrine hormones with insulin secretion. We
      hypothesized a relationship between circulating incretin concentrations and
      insulin secretion. METHODS: Subjects with normal glucose tolerance (NGT, n = 23),
      prediabetes (PDM, n = 17), or with type 2 diabetes (T2DM, n = 22) were studied
      twice, following a mixed test meal (470 kCal) (mixed meal tolerance test [MMTT])
      or intravenous L-arginine (arginine maximal stimulation test [AST], 5 g). GLP-1
      (total and active), PYY, GIP, glucagon, and beta cell function were measured
      before and following each stimulus. RESULTS: Baseline enteroendocrine hormones
      differed across the glucose tolerance (GT) spectrum, T2DM generally >NGT and PDM.
      In response to MMTT, total and active GLP-1, GIP, glucagon, and PYY increased in
      all populations. The incremental area-under-the-curve (0-120 min) of analytes
      like total GLP-1 were often higher in T2DM compared with NGT and PDM (35-51%; P <
      0.05). At baseline glucose, L-arginine increased total and active GLP-1 and
      glucagon concentrations in all GT populations (all P < 0.05). As expected, the
      MMTT and AST provoked differential glucose, insulin, and C-peptide responses
      across GT populations. Baseline or stimulated enteroendocrine hormone
      concentrations did not consistently correlate with either measure of beta cell
      function. CONCLUSIONS/INTERPRETATION: Both MMTT and AST resulted in insulin and
      enteroendocrine hormone responses across GT populations without consistent
      correlation between release of incretins and insulin, which is in line with other
      published research. If a defect is in the enteroendocrine/beta cell axis, it is
      probably reduced response to rather than diminished secretion of enteroendocrine
      hormones.

PMID- 30117765
TI  - Significance of fluctuations in serum sodium levels following aneurysmal
      subarachnoid hemorrhage: an exploratory analysis.
AB  - OBJECTIVE Fluctuations in patient serum sodium levels are common after aneurysmal
      subarachnoid hemorrhage (aSAH), but their effect on patient outcome is not well
      described in the literature. The goal of this work was to better characterize the
      relationship between fluctuations in serum sodium levels, outcome, and the
      development of delayed cerebral ischemia (DCI) after aSAH. METHODS The authors
      performed a post hoc analysis of data from the Clazosentan to Overcome
      Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage
      (CONSCIOUS-1) trial. Patients had their serum sodium values recorded daily for 14
      days post-aSAH. Average and average absolute daily differences in sodium levels
      were calculated for each patient based on 3 reference points: admission sodium
      levels, a normal sodium level (defined as 140 mmol/L), and the previous day's
      sodium level. These variables were also calculated for the classic "vasospasm
      window" (days 3-12) post-aSAH. A stepwise logistic regression model, locally
      weighted scatterplot smoothing curves, and receiver operator characteristic curve
      analysis were used to evaluate the relationship between alterations in serum
      sodium levels and clinical outcome or the development of DCI after aSAH. Poor
      outcome was defined as a modified Rankin Scale (mRS) score of > 2 at 3 months.
      RESULTS The average daily difference in sodium values from baseline (p < 0.001),
      average daily difference from a normal sodium level (p < 0.001), average absolute
      daily difference from a normal sodium level (p = 0.015), and average absolute
      daily difference from the previous day's sodium level (p = 0.017) were
      significant predictors of poor outcome in a stepwise multivariate regression
      model. There was a trend toward significance for average absolute daily
      difference from admission sodium levels during the vasospasm window as an
      independent predictor of DCI (p = 0.052). There was no difference in the
      predictive capacity for DCI when sodium fluctuations from post-aSAH days 1-14
      were compared with those from the classic vasospasm window (days 3-12).
      CONCLUSIONS Fluctuations in serum sodium levels may play a role in clinical
      outcome and the development of DCI after aSAH. The timing of these fluctuations
      appears to have no significant effect on the development of DCI.

PMID- 30117764
TI  - Safety of coiling with stent placement for the treatment of ruptured wide-necked
      intracranial aneurysms: a contemporary cohort study in a high-volume center after
      improvement of skills and strategy.
AB  - OBJECTIVE The authors compared the contemporary perioperative procedure-related
      complications between coiling with stent placement and coiling without stent
      placement for acutely ruptured aneurysms treated in a single center after
      improvement of interventional skills and strategy. METHODS In an institutional
      review board-approved protocol, 133 patients who underwent coiling with stent
      placement and 289 patients who underwent coiling without stent placement from
      January 2012 to December 2014 were consecutively reviewed retrospectively.
      Baseline characteristics, procedure-related complications and mortality rate,
      angiographic follow-up results, and clinical outcomes were compared between the
      two groups. Univariate analysis and logistic regression analysis were performed
      to determine the association of procedure-related complications of coiling with
      stent placement with potential risk factors. RESULTS The coiling/stent group and
      coiling/no-stent group were statistically comparable with respect to all baseline
      characteristics except for aneurysm location (p < 0.001) and parent artery
      configuration (p = 0.024). The immediate embolization results and clinical
      outcomes between the two groups showed no significant differences (p = 0.807 and
      p = 0.611, respectively). The angiographic follow-up results of the coiling in
      stent group showed a significant higher occlusion rate and lower recurrence rate
      compared with the coiling/no-stent group (82.5% vs 66.7%, 3.5% vs 14.5%, p =
      0.007). Procedure-related intraoperative rupture and thrombosis, postoperative
      early rebleeding and thrombosis, and external ventricular drainage-related
      hemorrhagic event occurred in 3.0% (4 of 133), 2.3% (3 of 133), 1.5% (2 of 133),
      0.7% (1 of 133), and 0.8% (1 of 133) of the coiling/stent group compared with
      1.0% (3 of 289), 1.4% (4 of 289), 1.4% (4 of 289), and 0.7% (2 of 289) of the
      coiling/no-stent group, respectively (p = 0.288, p = 0.810, p = 1.000, p = 0.315,
      and p = 1.000, respectively). One patient presented with coil protrusion in the
      group of coiling without stent. The procedure-related mortality was 1.5% (2 of
      133) in the coiling/stent group and 0.7% in the coiling/no-stent group (p =
      0.796). Multivariable analysis showed no significant predictors for the total
      perioperative procedure-related complications, hemorrhagic complications, or
      ischemic complications. CONCLUSIONS The perioperative procedure-related
      complications and mortality rate did not differ significantly between the
      coiling/stent group and the coiling/no-stent group for patients with acutely
      ruptured aneurysms. Considering the better angiographic follow-up results,
      coiling with stent placement might be a feasible, safe, and promising option for
      treatment in the acute phase of selected wide-necked ruptured intracranial
      aneurysms.

PMID- 30117766
TI  - Long-term outcomes among octogenarians with aneurysmal subarachnoid hemorrhage.
AB  - OBJECTIVE Data evaluating the long-term outcomes, particularly with regard to
      treatment modality, of aneurysmal subarachnoid hemorrhage (SAH) in octogenarians
      are limited. The primary objectives were to evaluate the disposition (living at
      home vs institutional settings) and analyze the predictors of long-term survival
      and return to home for octogenarians after SAH. METHODS Data pertaining to
      patients age 80 and older who underwent microsurgical clipping or endovascular
      coiling for SAH were extracted from 100% nationwide Medicare inpatient claims and
      linked with the Minimum Data Set (2008-2011). Patient disposition was tracked for
      2 years after index SAH admission. Multivariable logistic regression stratified
      by aneurysm treatment modality, and adjusted for patient factors including SAH
      severity, evaluated predictors of return to home at 60 and 365 days after SAH.
      Survival 365 days after SAH was analyzed with a multivariable Cox proportional
      hazards model. RESULTS A total of 1298 cases were included in the analysis. One
      year following SAH, 56% of the patients had died or were in hospice care, 8% were
      in an institutional post-acute care setting, and 36% had returned home. Open
      microsurgical clipping (adjusted hazard ratio [aHR] 0.67, 95% confidence interval
      [CI] 0.54-0.81), male sex (aHR 0.70, 95% CI 0.57-0.87), tracheostomy (aHR 0.63,
      95% CI 0.47-0.85), gastrostomy (aHR 0.60, 95% CI 0.48-0.76), and worse SAH
      severity (aHR 0.94, 95% CI 0.92-0.97) were associated with reduced likelihood of
      patients ever returning home. Older age (aHR 1.09, 95% CI 1.05-1.13),
      tracheostomy (aHR 2.06, 95% CI 1.46-2.91), gastrostomy (aHR 1.55, 95% CI 1.14
      2.10), male sex (aHR 1.66, 95% CI 1.20-2.23), and worse SAH severity 1.51 (95% CI
      1.04-2.18) were associated with reduced survival. CONCLUSIONS In this national
      analysis, 56% of octogenarians with SAH died, and 36% returned home within 1 year
      of SAH. Coil embolization predicted returning to home, which may suggest a
      benefit to endovascular treatment in this patient population.

PMID- 30117767
TI  - Professionalism and performance issues during neurosurgical training and job
      satisfaction after training: a single training center 50-year experience.
AB  - OBJECTIVE Neurosurgery is often self-selecting. Concern has been raised that
      residents in the millennial era (born between 1982 and 2004) may have more
      serious professionalism and performance issues (PPIs) during training compared to
      prior trainees. Serious PPIs were defined as concerns that led to specific
      resident disciplinary actions ranging from initial warnings to termination. In
      order to evaluate this concern, the authors retrospectively reviewed a 50-year
      experience at a single training center. They then prospectively surveyed living
      graduates of the program to assess variations in practice patterns and job
      satisfaction over 5 decades. METHODS The PPIs of 141 residents admitted for
      training at the University of Pittsburgh (subsequently UPMC) Department of
      Neurological Surgery were reviewed by decade starting in 1971 when the first
      department chair was appointed. The review was conducted by the senior author,
      who served from 1975 to 1980 as a resident, as a faculty member since 1980, and
      as the resident director since 1986. A review of resident PPIs between 1971 and
      1974 was performed in consultation with a senior faculty member active at that
      time. During the last decade, electronic reporting of PPIs was performed by entry
      into an electronic reporting system. In order to further evaluate whether the
      frequency of PPIs affected subsequent job satisfaction and practice patterns
      after completion of training, the authors surveyed living graduates. RESULTS
      There was no statistically significant difference by decade in serious PPIs.
      Although millennial residents had no significant increase in the reporting of
      serious PPIs, the increased use of electronic event reporting over the most
      recent 2 decades coincided with a trend of increased reporting of all levels of
      suspected PPIs (p < 0.05). Residents surveyed after completion of training showed
      no difference by decade in types of practice or satisfaction-based metrics (p >
      0.05) but reported increasing concerns related to the impact of their profession
      on their own lifestyle as well as their family's. CONCLUSIONS There was no
      statistically significant difference in the incidence of serious PPIs over 5
      decades of training neurosurgery residents at the authors' institution. During
      the millennial era, serious PPIs have not been increasing. However, reporting of
      all levels of PPIs is increasing coincident with the ease of electronic
      reporting. There was remarkably little variance in satisfaction metrics or type
      of practice over the 5 decades studied.

PMID- 30117768
TI  - Upfront Gamma Knife radiosurgery for Cushing's disease and acromegaly: a
      multicenter, international study.
AB  - OBJECTIVE Gamma Knife radiosurgery (GKS) is typically used after failed resection
      in patients with Cushing's disease (CD) and acromegaly. Little is known about the
      upfront role of GKS for patients with CD and acromegaly. In this study, the
      authors examine the outcome of upfront GKS for patients with these functioning
      adenomas. METHODS An international group of 7 Gamma Knife centers sent pooled
      data from 46 patients (21 with CD and 25 with acromegaly) undergoing upfront GKS
      to the coordinating center of the study for analysis. Diagnosis was established
      on the basis of clinical, endocrine, and radiological studies. All patients were
      treated on a common radiosurgical platform and longitudinally followed for tumor
      control, endocrine remission, and hypopituitarism. Patients received a tumor
      median margin dose of 25 Gy (range 12-40.0 Gy) at a median isodose of 50%.
      RESULTS The median endocrine follow-up was 69.5 months (range 9-246 months).
      Endocrine remission was achieved in 51% of the entire cohort, with 28% remission
      in acromegaly and 81% remission for those with CD at the 5-year interval.
      Patients with CD achieved remission earlier as compared to those with acromegaly
      (p = 0.0005). In patients post-GKS, the pituitary adenoma remained stable (39%)
      or reduced (61%) in size. Hypopituitarism occurred in 9 patients (19.6%), and 1
      (2.2%) developed third cranial nerve (CN III) palsy. Eight patients needed
      further intervention, including repeat GKS in 6 and transsphenoidal surgery in 2.
      CONCLUSIONS Upfront GKS resulted in good tumor control as well as a low rate of
      adverse radiation effects in the whole group. Patients with CD achieved a faster
      and far better remission rate after upfront GKS in comparison to patients with
      acromegaly. GKS can be considered as an upfront treatment in carefully selected
      patients with CD who are unwilling or unable to undergo resection, but it has a
      more limited role in acromegaly.

PMID- 30117769
TI  - Pain-free and pain-controlled survival after sectioning the nervus intermedius in
      nervus intermedius neuralgia: a single-institution review.
AB  - OBJECTIVE Nervus intermedius neuralgia (NIN) or geniculate neuralgia is a rare
      facial pain condition consisting of sharp, lancinating pain deep in the ear and
      can occur alongside trigeminal neuralgia (TN). Studies on the clinical
      presentation, intraoperative findings, and ultimately postoperative outcomes are
      extremely limited. The aim of this study was to examine the clinical presentation
      and surgical findings, and determine pain-free survival after sectioning of the
      nervus intermedius (NI). METHODS The authors conducted a retrospective chart
      review and survey of patients who were diagnosed with NIN at one institution and
      who underwent neurosurgical interventions. Pain-free survival was determined
      through chart review and phone interviews using a modified facial pain and
      quality of life questionnaire and represented as Kaplan-Meier curves. RESULTS The
      authors found 15 patients with NIN who underwent microsurgical intervention
      performed by two surgeons from 2002 to 2016 at a single institution. Fourteen of
      these patients underwent sectioning of the NI, and 8 of 14 had concomitant TN.
      Five patients had visible neurovascular compression (NVC) of the NI by the
      anterior inferior cerebellar artery in most cases where NVC was found. The most
      common postoperative complaints were dizziness and vertigo, diplopia, ear
      fullness, tinnitus, and temporary facial nerve palsy. Thirteen of the 14 patients
      reportedly experienced pain relief immediately after surgery. The mean length of
      follow-up was 6.41 years (range 8 months to 14.5 years). Overall recurrence of
      any pain was 42% (6 of 14), and 4 patients (isolated NIN that received NI
      sectioning alone) reported their pain was the same or worse than before surgery
      at longest follow-up. The median pain-free survival was 4.82 years +/- 14.85
      months. The median pain-controlled survival was 6.22 years +/- 15.78 months.
      CONCLUSIONS In this retrospective review, sectioning of the NI produced no major
      complications, such as permanent facial weakness or deafness, and was effective
      for patients when performed in addition to other procedures. After sectioning of
      the NI, patients experienced 4.8 years pain free and experienced 6.2 years of
      less pain than before surgery. Alone, sectioning of the NI was not effective. The
      pathophysiology of NIN is not entirely understood. It appears that neurovascular
      compression plays only a minor role in the syndrome and there is a high degree of
      overlap with TN.

PMID- 30117770
TI  - Subcortical stimulation mapping of descending motor pathways for perirolandic
      gliomas: assessment of morbidity and functional outcome in 702 cases.
AB  - OBJECTIVE Herein, the authors report their experience with intraoperative
      stimulation mapping to locate the descending subcortical motor pathways in
      patients undergoing surgery for hemispheric gliomas within or adjacent to the
      rolandic cortex, with particular description of the morbidity and functional
      outcomes associated with this technique. METHODS This is a retrospective analysis
      of patients who, in the period between 1997 and 2016, had undergone resection of
      hemispheric perirolandic gliomas within or adjacent to descending motor pathways.
      Data regarding intraoperative stimulation mapping and patient postoperative
      neurological status were collected. RESULTS Of 702 patients, stimulation mapping
      identified the descending motor pathways in 300 cases (43%). A new or worsened
      motor deficit was seen postoperatively in 210 cases (30%). Among these 210 cases,
      there was improvement in motor function to baseline levels by 3 months
      postoperatively in 161 cases (77%), whereas the deficit remained in 49 cases
      (23%). The majority (65%) of long-term deficits (persisting beyond 3 months) were
      mild or moderate (antigravity strength or better). On multivariate analysis,
      patients in whom the subcortical motor pathways had been identified with
      stimulation mapping during surgery were more likely to develop an additional
      and/or worsened motor deficit postoperatively than were those in whom the
      subcortical pathways had not been found (45% vs 19%, respectively, p < 0.001).
      This difference remained when considering the likelihood of a long-term deficit
      (i.e., persisting > 3 months; 12% vs 3.2%, p < 0.001). A higher tumor grade and
      the presence of a preoperative motor deficit were also associated with higher
      rates of motor deficits persisting long-term. A region of restricted diffusion
      adjacent to the resection cavity was seen in 20 patients with long-term deficits
      (41%) and was more common in cases in which the motor pathways were not
      identified (69%). Long-term deficits that occur in settings in which the
      subcortical motor pathways are not identified seem in large part due to ischemic
      injury to descending tracts. CONCLUSIONS Stimulation mapping allows surgeons to
      identify the descending motor pathways during resection of tumors in perirolandic
      regions and to attain an acceptable rate of morbidity in these high-risk cases.

PMID- 30117771
TI  - Multimodal management of arteriovenous malformations of the basal ganglia and
      thalamus: factors affecting obliteration and outcome.
AB  - OBJECTIVE Arteriovenous malformations (AVMs) of the basal ganglia and thalamus
      are particularly difficult lesions to treat, accounting for 3%-13% of all AVMs in
      surgical series and 23%-44% of malformations in radiosurgery series. The goal of
      this study was to report the results of multimodal management of basal ganglia
      and thalamic AVMs and investigate the factors that influence radiographic cure
      and good clinical outcomes. METHODS This study was a retrospective analysis of a
      prospectively maintained database of all patients treated at the authors'
      institution. Clinical, radiological, follow-up, and outcome data were analyzed.
      Univariate and multivariate analyses were conducted to explore the influence of
      various factors on outcome. RESULTS The results and data analysis pertaining to
      123 patients treated over 32 years are presented. In this cohort, radiographic
      cure was achieved in 50.9% of the patients. Seventy-five percent of patients had
      good clinical outcomes (stable or improved performance scores), whereas 25%
      worsened after treatment. Inclusion of surgery and radiosurgery independently
      predicted obliteration, whereas nidus diameter and volume predicted clinical
      outcomes. Nidus volume/diameter and inclusion of surgery predicted the optimal
      outcome, i.e., good clinical outcomes with lesion obliteration. CONCLUSIONS Good
      outcomes are possible with multimodal treatment in these complex patients.
      Increasing size and, by extension, higher Spetzler-Martin grade are associated
      with worse outcomes. Inclusion of multiple modalities of treatment as indicated
      could improve the chances of radiographic cure and good outcomes.

PMID- 30117772
TI  - Letter to the Editor. Phase III randomized controlled trials are essential to
      properly evaluate the role of radiotherapy in WHO grade II meningioma.

PMID- 30117773
TI  - Early postsurgical diffusivity metrics for prognostication of long-term pain
      relief after Gamma Knife radiosurgery for trigeminal neuralgia.
AB  - OBJECTIVE Gamma Knife radiosurgery (GKRS) is an important treatment modality for
      trigeminal neuralgia (TN). Current longitudinal assessment after GKRS relies
      primarily on clinical diagnostic measures, which are highly limited in the
      prediction of long-term clinical benefit. An objective, noninvasive, predictive
      tool would be of great utility to advance the clinical management of patients.
      Using diffusion tensor imaging (DTI), the authors' aim was to determine whether
      early (6 months post-GKRS) target diffusivity metrics can be used to
      prognosticate long-term pain relief in patients with TN. METHODS Thirty-seven
      patients with TN treated with GKRS underwent 3T MRI scans at 6 months
      posttreatment. Diffusivity metrics of fractional anisotropy, axial diffusivity,
      radial diffusivity, and mean diffusivity were extracted bilaterally from the
      radiosurgical target of the affected trigeminal nerve and its contralateral,
      unaffected nerve. Early (6 months post-GKRS) diffusivity metrics were compared
      with long-term clinical outcome. Patients were identified as long-term responders
      if they achieved at least 75% reduction in preoperative pain for 12 months or
      longer following GKRS. RESULTS Trigeminal nerve diffusivity at 6 months post-GKRS
      was predictive of long-term clinical effectiveness, where long-term responders (n
      = 19) showed significantly lower fractional anisotropy at the radiosurgical
      target of their affected nerve compared to their contralateral, unaffected nerve
      and to nonresponders. Radial diffusivity and mean diffusivity, correlates of
      myelin alterations and inflammation, were also significantly higher in the
      affected nerve of long-term responders compared to their unaffected nerve.
      Nonresponders (n = 18) did not exhibit any characteristic diffusivity changes
      after GKRS. CONCLUSIONS The authors demonstrate that early postsurgical target
      diffusivity metrics have a translational, clinical value and permit prediction of
      long-term pain relief in patients with TN treated with GKRS. Importantly, an
      association was found between the footprint of radiation and clinical
      effectiveness, where a sufficient level of microstructural change at the
      radiosurgical target is necessary for long-lasting pain relief. DTI can provide
      prognostic information that supplements clinical measures, and thus may better
      guide the postoperative assessment and clinical decision-making for patients with
      TN.

PMID- 30117774
TI  - Attitudes and opinions of US neurosurgical residents toward research and
      scholarship: a national survey.
AB  - OBJECTIVE The analysis of resident research productivity in neurosurgery has
      gained significant recent interest. Resident scholarly output affects
      departmental productivity, recruitment of future residents, and likelihood of
      future research careers. To maintain and improve opportunities for resident
      research, the authors evaluated factors that affect resident attitudes toward
      neurosurgical research on a national level. METHODS An online survey was
      distributed to all US neurosurgical residents. Questions assessed interest in
      research, perceived departmental support of research, and resident-perceived
      limitations in pursuing research. Residents were stratified based on number of
      publications above the median (AM; >= 14) or below the median (BM; < 14) for
      evaluation of factors influencing productivity. RESULTS A total of 278 resident
      responses from 82 US residency programs in 30 states were included (a 20% overall
      response rate). Residents predominantly desired future academic positions
      (53.2%), followed by private practice with some research (40.3%). Residents
      reported a mean +/- SD of 11 +/- 14 publications, which increased with
      postgraduate year level. The most common type of research involved retrospective
      cohort studies (24%) followed by laboratory/benchtop (19%) and case reports
      (18%). Residents as a group spent on average 14.1 +/- 18.5 hours (median 7.0
      hours) a week on research. Most residents (53.6%) had >= 12 months of protected
      research time. Mentorship (92.4%), research exposure (89.9%), and early interest
      in science (78.4%) had the greatest impact on interest in research while the most
      limiting factors were time (91.0%), call scheduling (47.1%), and funding/grants
      (37.1%). AM residents cited research exposure (p = 0.003), neurosurgery
      conference exposure (p = 0.02), formal research training prior to residency (p =
      0.03), internal funding sources (p = 0.05), and software support (p = 0.02) as
      most important for their productivity. Moreover, more productive residents
      applied and received a higher number of < $10,000 and >= $10,000 grants (p <
      0.05). A majority of residents (82.4%) agreed or strongly agreed with pursuing
      research throughout their professional careers. Overall, about half of residents
      (49.6%) were encouraged toward continued neurosurgical research, while the rest
      were neutral (36.7%) or discouraged (13.7%). Free-text responses helped to
      identify solutions on a departmental, regional, and national level that could
      increase interest in neurosurgical research. CONCLUSIONS This survey evaluates
      various factors affecting resident views toward research, which may also be seen
      in other specialties. Residents remain enthusiastic about neurosurgical research
      and offer several solutions to the ever-scarce commodities of time and funding
      within academic medicine.

PMID- 30117775
TI  - Conflict of interest policies and disclosure requirements in neurosurgical
      journals.
AB  - OBJECTIVE An increasing amount of funding in neurosurgery research comes from
      industry, which may create a conflict of interest (COI) and the potential to bias
      results. The reporting and handling of COIs have become difficult, particularly
      as explicit policies themselves and definitions thereof continue to vary between
      medical journals. In this study, the authors sought to evaluate the prevalence
      and comprehensiveness of COI policies among leading neurosurgical journals.
      METHODS The authors conducted a cross-sectional study of publicly available
      online disclosure policies in the 20 highest-ranking neurosurgical journals, as
      determined by Google Scholar Metrics, in July 2016. RESULTS Overall, 89.5% of the
      highest-impact neurosurgical journals included COI policy statements. Ten (53%)
      journals requested declaration of nonfinancial conflicts, while 2 journals
      specifically set a time period for COIs. Sixteen journals required declaration
      from the corresponding author, 13 from all authors, 6 from reviewers, and 5 from
      editors. Four journals were included in the International Committee of Medical
      Journal Editors (ICMJE) list of publications that follow the Uniform Requirements
      for Manuscripts Submitted to Biomedical Journals (currently known as
      Recommendations for the Conduct, Reporting, Editing, and Publication of Scholarly
      Work in Medical Journals). Five journal policies included COI declaration
      verification, management, or enforcement. The neurosurgery journals with more
      comprehensive COI policies were significantly more likely to have higher h5
      indices (p = 0.003) and higher impact factors (p = 0.01). CONCLUSIONS In 2016,
      the majority of, but not all, high-impact neurosurgical journals had publically
      available COI disclosure policies. Policy inclusiveness and comprehensiveness
      varied substantially across neurosurgical journals, but COI comprehensiveness was
      associated with other established markers of individual journals' favorability
      and influence, such as impact factor and h5-index.

PMID- 30117776
TI  - Reuniting Families Using Genetic Testing?

PMID- 30117777
TI  - A Preliminary Study on Metadherin as a Potential Marker for Progression of
      Diffuse Large B Cell Lymphoma.
AB  - AIMS: To determine if Metadherin (MTDH) expression levels are positively
      correlated with the clinical stage of diffuse large B-cell lymphoma (DLBCL) based
      on MTDH being highly expressed in other type of tumors including melanoma,
      malignant glioma, breast cancer, and hepatocellular carcinoma. In this study, we
      investigated the pathologic significance of MTDH and its potential in predicting
      DLBCL outcomes. MATERIALS AND METHODS: Tissue samples from 50 patients with DLBCL
      and 22 patients with lymph node reactive hyperplasia were collected and evaluated
      using immunohistochemical staining, microscopy, and western blotting. The Kaplan
      Meier method and Cox regression model were used for survival analysis of
      patients. RESULTS: Our results show that the overexpression of the MTDH protein
      in tissues was observed in 66% of patients with DLBCL, whereas it was not
      overexpressed in the patients with reactive hyperplastic lymph nodes. While there
      was no correlation between MTDH overexpression with age, sex, presence of B
      symptoms, and lactate dehydrogenase (LDH) levels in patients with DLBCL, this
      parameter was positively correlated with clinical stages. Moreover, MTDH-negative
      patients had significantly better prognoses compared with the MTDH-positive
      patients. CONCLUSION: Our preliminary study indicates that MTDH may play an
      important role in the development of DLBCL, and that MTDH overexpression is
      potentially associated with the clinical progression of DLBCL. In addition, high
      expression levels of MTDH in tissues was correlated with a poorer prognosis for
      patients with DLBCL. As such, MTDH may be a potential therapeutic target for
      specific therapy. However, research on a larger group of patients is needed to
      verify these preliminary results.

PMID- 30117778
TI  - Mutation Screening of the EDA Gene in Seven Chinese Families with X-Linked
      Hypohidrotic Ectodermal Dysplasia.
AB  - BACKGROUND: As the most common form of ectodermal dysplasia (ED), X-linked
      hypohidrotic ED (XLHED) is characterized by the triad of hypohidrosis,
      hypotrichosis, and anodontia in male patients. The gene responsible for XLHED is
      EDA. To date, more than 300 mutations have been identified in this gene,
      including point mutations, deletions, and insertions. Most of the mutations
      result in XLHED, while the rest cause X-linked dominant incisor hypodontia.
      OBJECTIVE: Mutation screening was performed in seven Chinese families with XLHED.
      RESULTS: Mutations were identified in all seven families, including four
      previously reported missense mutations (p.M1T, p.R156C, p.G299S, and p.A349T) and
      three novel mutations; missense mutation (p.Q358 L), indel (P228Tfs*52), as well
      as a large deletion. CONCLUSION: Our results extend the mutational spectrum of
      EDA and can be helpful with genetic counseling and prenatal diagnosis for these
      families.

PMID- 30117779
TI  - Association Between Matrix Metalloproteinase-1, 2, 3 Polymorphisms and Oral
      Cancer Risk: A Meta-Analysis.
AB  - PURPOSE: Numerous studies have estimated the association between matrix
      metalloproteinases (MMPs) polymorphisms and the risk of oral cancer; the results,
      however, are inconsistent and conflicting. Therefore, we conducted a meta
      analysis to evaluate the association of MMP-1, 2, and 3 polymorphisms with oral
      cancer risk. METHODS: A computerized literature search was conducted of
      electronic databases and search engines. Odds ratios (OR) and 95% confidence
      intervals (CI) were calculated for each gene, and the heterogeneity among studies
      was estimated using the Q-test and I2 values. Overall and subgroup analyses were
      undertaken. Statistical analyses were conducted using Review Manager v5.3 and
      Stata v12.0 software. RESULTS: Eighteen studies were included in this meta
      analysis. For MMP-1(-1607) 1G/2G, a significant association was observed using
      the recessive genetic model (OR = 1.47; 95% CI = 1.14-1.91; I2 = 64%,
      pheterogeneity = 0.003). In the subgroup studies, a significant association was
      observed in the Asian subgroup (OR = 1.68; 95% CI = 1.42-1.99; I2 = 17%,
      pheterogeneity = 0.30 for the recessive model; and OR = 1.59; 95% CI = 1.19-2.13;
      I2 = 80%, pheterogeneity < 0.00001 for the allelic contrast model) and in the
      European subgroup (OR = 0.65; 95% CI = 0.44-0.98; I2 = 21%, pheterogeneity = 0.26
      for the allelic contrast model). No significant associations were observed with
      either MMP-2(-1306) C/T or MMP-3(-1171) 5A/6A. CONCLUSIONS: The MMP-1(-1607)
      1G/2G polymorphism is associated with oral cancer risk, and the 2G allele played
      different roles in Asian and European populations.

PMID- 30117780
TI  - MOLECULAR AND MORPHOLOGICAL DISCRIMINATION OF DICROCOELIID LARVAE (TREMATODA:
      DIGENEA) FROM TERRESTRIAL MOLLUSKS IN JAPAN.
AB  - Trematodes of the family Dicrocoeliidae commonly use terrestrial mollusks as the
      first intermediate host. Despite the abundant studies on the adult worms in birds
      and mammals, few reports exist on their larval stage in snail intermediate hosts.
      A present survey of mollusks in Japan led us to the discovery of dicrocoeliid
      sporocysts with cercariae in 16 out of 303 individuals, encompassing eight snail
      species and one slug species. A DNA barcoding based on sequencing of
      mitochondrial cytochrome c oxidase subunit 1 showed that the larvae consisted of
      five species. Phylogenetic trees of nuclear 18S and 28S ribosomal DNAs confirmed
      the five species to be members of the Dicrocoeliidae. These were temporarily
      termed dicrocoeliid spp. 1 to 5, since conclusive identification was impossible
      without adult worms. These unknown species were phylogenetically related to each
      other, except sp. 5. The phylogenetic trees demonstrated close genetic
      relationships between sp. 3 and the genus Lutztrema, and between sp. 5 and the
      genus Lyperosomum. The phylogenetic analysis also suggested that a division into
      the subfamilies Dicrocoeliinae and Leipertrematinae is a wrong classification due
      to the paraphyly of the Dicrocoeliinae. Morphological characterization of the
      cercariae and their DNA barcodes provide a primary platform for differentiating
      dicrocoeliids from various mollusks in Japan. The DNA barcodes, in particular,
      will enable tracing the parasite life cycles, in case of finding metacercariae
      and adults from presently unknown hosts.

PMID- 30117781
TI  - Trauma and Mental Health in Resettled Refugees: Mediating Effect of Host Language
      Acquisition on Posttraumatic Stress Disorder, Depressive and Anxiety Symptoms.
AB  - This study examined the relationship between traumatic exposure, host language
      acquisition and mental health (posttraumatic stress, depressive and anxiety
      symptoms) in long-term resettled refugees. Participants included a community
      sample of Bosnian refugees ( N = 138, 55% male, mean age of 40 years old) that
      had resettled in Australia and Austria on average 18 years prior. Two mediation
      models were tested based on two competing theories. Model A examined whether
      language acquisition mediates the relationship between traumatic exposure and
      mental health problems experienced by refugees. Model B examined whether mental
      health symptoms mediate the relationship between exposure to traumatic events and
      the acquisition of host language. Model A fit the data well (CFI = 1.00, SRMR =
      .017, RMSEA < .001, chi2 p = .526), while Model B was rejected as an acceptable
      model for the data (CFI = .556, SRMR = .136, RMSEA = .352). In Model A, the
      indirect pathway from trauma to mental health via language acquisition was
      significant for PTSD ( beta = .067, p = .028) and anxiety symptoms ( beta = .063,
      p = .026) but not depression symptoms ( beta = .048, p = .071). Intervention
      strategies aimed at improving host language acquisition may be important not only
      in successful adaptation to daily living in the host country, but also to improve
      the mental health of traumatized refugees.

PMID- 30117782
TI  - Perspectives on cervical cancer screening and prevention: challenges faced by
      providers and patients along the Texas-Mexico border.
AB  - BACKGROUND: The Rio Grande Valley (RGV) and Laredo regions located along the
      Texas-Mexico border consist of seven counties with a population of approximately
      1.5 million people and a high uninsured rate (33.5%). Cervical cancer mortality
      in these border counties is approximately 30% higher than the rest of Texas. The
      RGV and Laredo areas were studied to better understand the state of access to
      cervical cancer prevention services along the Texas-Mexico border. METHODS: Data
      on the population served and the services provided were analyzed to determine the
      gap between cervical cancer screenings recommended versus those received. Through
      interviews, we gathered the perspectives of 16 local stakeholders regarding
      cervical cancer screening for underserved individuals in the region. FINDINGS: It
      is estimated that 69,139 uninsured women aged 21-64 years in the RGV/Laredo per
      year are recommended to undergo cervical cancer screening with Papanicolaou (Pap)
      and/or human papillomavirus (HPV) testing, but only 8941 (12.9%) Pap tests are
      being performed by the Federally Qualified Health Center (FQHC) serving uninsured
      women in these regions. Systemic barriers identified include insufficient
      provider clinical capacity, the high cost of healthcare, and uncertainty about
      government funding sources. Patient barriers identified include inadequate
      knowledge on navigating the local healthcare system, low health literacy, lack of
      money and childcare, an inability to miss work, limited transportation, and fear
      of deportation. CONCLUSION: Decreasing the disparity between cervical cancer
      screening services provided and those recommended requires addressing the
      barriers, identified by local experts, which prevent uninsured women from
      accessing care. These challenges are being addressed through ongoing programs and
      collaborations.

PMID- 30117784
TI  - Comparing in-the-moment skill coaching effects from tailored versus non-tailored
      acceptance and commitment therapy mobile apps in a non-clinical sample.
AB  - Mobile apps are promising for teaching how to practice psychological skills in
      high-risk and in vivo momentary situations, but there has been minimal research
      on the immediate effects of app-based skill coaching on mental health in-the
      moment. This study analyzed the mobile app data in a non-clinical sample of 39
      adults participating in a larger randomized controlled trial, with participants
      randomized to an acceptance and commitment therapy (ACT) mobile app that tailors
      skill coaching based on in-the-moment variables (n = 17) or an app that provides
      randomly selected skill coaching (n = 22). Data were collected before and after
      each ACT skill coaching session on proximal outcome (depression, anxiety, and
      engagement in meaningful activity) and ACT process variables. Multilevel models
      indicated significant immediate improvements on average following ACT skill
      coaching sessions on all proximal outcome and ACT process variables, although
      with relatively small effects ranging between 0.17 and 0.27 SD units change.
      Larger immediate pre-to-post effects from ACT coaching sessions were found for
      anxiety, experiential avoidance, and cognitive fusion in the tailored app versus
      random app condition. Overall, results suggest that an ACT app can have
      immediate, in-the-moment effects on psychological functioning, which may be
      enhanced by tailoring skills to current context.

PMID- 30117783
TI  - A Potential Biomarker for Predicting the Risk of Radiation-Induced Fibrosis in
      the Lung.
AB  - Biomarkers could play an essential role during triage in the aftermath of a
      radiological event, where exposure to radiation will be heterogeneous and
      complicated by concurrent trauma. Used alongside biodosimetry, biomarkers can
      identify victims in need of treatment for acute radiation effects, and might also
      provide valuable information on later developing consequences that need to be
      addressed as part of a treatment strategy. Indeed, because the lung is
      particularly sensitive to radiation and resultant late effects not only affect
      quality of life, but can also lead to morbidity, the risk of developing
      downstream pulmonary complications in exposed individuals requires assessment. In
      this study, analyses of changes in pulmonary and circulating content of club cell
      secretory protein (CCSP) and surfactant protein D (SP-D), expressed by epithelial
      club cells and type II pneumocytes in the lung, respectively, were used to
      evaluate pulmonary epithelial damage in several lung injury models. Using a
      combined radiation exposure model, fibrosis-susceptible C57BL/6J (C57) and
      alveolitis-prone C3H/HeJ (C3H) mice received 5 Gy total-body irradiation plus 2.5
      10 Gy whole-lung irradiation, and lung and plasma samples were collected
      throughout the course of the radiation response, at time points ranging from 24 h
      to 26 weeks postirradiation. Radiation significantly reduced bronchiole CCSP
      coverage in C57 mice at 26 weeks, a response that varied in extent among animals,
      but correlated with the severity of fibrosis in each animal. Interestingly,
      plasma CCSP content was elevated in C57 mice at multiple time points preceding
      and during the fibrotic period; this response that was not observed in C3H mice.
      Circulating CCSP/SP-D ratios, calculated as an index of lung integrity, were
      similarly increased throughout the time course in C57, but not C3H, mice.
      Furthermore, when the thoracic doses were reduced to subthreshold levels for
      fibrosis induction (2.5 or 7.5 Gy), although the CCSP/SP-D ratio in lung
      homogenates demonstrated dose-responsive changes, this was not reflected in the
      plasma ratios at acute and late time points. Importantly, plasma CCSP/SP-D ratios
      also were not significantly altered in C57 mice exposed to LPS, and only
      transiently decreased in influenza-exposed mice, demonstrating a level of
      specificity for radiation-induced lung injury. These results indicate that the
      CCSP/SP-D ratio, measured in plasma, is sensitive to individual variation in
      radiation sensitivity, correlates with fibrosis development, can be detected
      early after exposure and is specific to radiation-induced injury. This suggests
      that the CCSP/SP-D ratio may be useful as a biomarker of radiation-induced
      pulmonary fibrosis.

PMID- 30117785
TI  - Metastatic thymoma in the liver of a dog.
AB  - A 12-y-old neutered male Portuguese Water dog was presented because of a 1-y
      history of persistent hyporexia, diarrhea, and recurrent pyelonephritis.
      Abdominal ultrasound revealed hepatic nodules and diffuse splenomegaly, and
      radiographs revealed a mediastinal mass. Fine-needle aspirates of the liver,
      spleen, and mediastinal mass were suspicious for lymphoma. Flow cytometry
      identified small T cells that co-expressed CD4 and CD8 at all sites, most
      suspicious for thymoma, but lymphoma could not be ruled out. PCR for antigen
      receptor rearrangements analysis identified polyclonal amplification of the T
      cell receptor genes, more consistent with thymoma than lymphoma. Histopathology
      of the liver and thymic mass confirmed thymoma with hepatic metastasis.

PMID- 30117786
TI  - First Report of Grapevine rupestris vein feathering virus in grapevine in
      Germany.

PMID- 30117787
TI  - Discrepant Clinical Significance of CD28+CD8- and CD4+CD25high Regulatory T Cells
      During the Progression of Hepatitis B Virus Infection.
AB  - Accumulating evidence demonstrates that CD8+CD28- regulatory T cells increase in
      chronic viral infection as well as tumorigenesis. However, it is still not clear
      about their characteristics in hepatitis B virus (HBV) infection. In addition, it
      is not understood whether this regulatory immune subset is distinct from
      CD4+CD25high regulatory T cells in the aspect of impact on or relationship to the
      progression of HBV infection. Hence, we investigated their dynamics and compared
      their correlations with clinical parameters in the chronic and advanced phases of
      HBV infection. The data showed that compared with healthy controls, the
      frequencies of CD28+CD8- and CD4+CD25high T cells increased in both chronic and
      advanced phases, while there is no significant difference between the two case
      groups. Interestingly, we found that in chronic phase, the frequency of CD8+CD28-
      subset was negatively correlated with the levels of alanine aminotransaminase
      (ALT) and aspartate aminotransferase (AST), respectively, and did not present
      association with HBV DNA load, whereas that of CD4+CD25high T cells was
      positively correlated with HBV DNA load and the levels of ALT and AST,
      respectively. Amazingly, in advanced phase, the frequency of CD4+CD25high T cells
      was negatively correlated with HBV DNA load and the levels of ALT, respectively,
      while there is no significant correlation between the frequency of CD8+CD28-
      subset and those clinical parameters. Thereby, our findings demonstrated that
      CD28+CD8- and CD4+CD25high regulatory T cells might exert distinct effect on
      modulating antiviral immune responses and mitigate immunomediated liver damage in
      different phases of HBV infection, which represent potential prognostic markers
      and therapeutic targets for HBV-infected patients based on further exploration of
      detailed mechanism.

PMID- 30117788
TI  - Long-term disability after stroke in Iran: Evidence from the Mashhad Stroke
      Incidence Study.
AB  - Background Accurate information about disability rate after stroke remains
      largely unclear in many countries. Population-based studies are necessary to
      estimate the rate and determinants of disability after stroke. Methods Patients
      were recruited from the Mashhad Stroke Incidence Study and followed for five
      years after their index event. Disability was measured using the modified Rankin
      scale and functional dependency was measured using the Barthel index. Results
      Among 684 patients registered in this study, 624 were first-ever strokes. In
      total, 69.0% (n = 409) of patients either died or remained disabled at five-year
      follow-up. Among the first-ever stroke survivors, 18.5% (n = 69) at one year and
      15.9% (n = 31) at five years required major assistance in their daily activities.
      Patients with a history of stroke (before the study period) compared with first
      ever strokes were more likely to be disabled at one year (modified Rankin scale>2
      in 40.0% vs. 19.1%; P < 0.001). Advanced age, severity of stroke at the time of
      admission, diabetes mellitus, and educational level (<12 years) were
      independently associated with greater disability and functional dependency.
      Conclusion We found that significant disability and functional dependency after
      stroke in Northeast Iran were largely attributable to the effects of stroke
      severity and prior dependency.

PMID- 30117789
TI  - Robot-guided pediatric stereoelectroencephalography: single-institution
      experience.
AB  - OBJECTIVE Stereoelectroencephalography (SEEG) has increased in popularity for
      localization of epileptogenic zones in drug-resistant epilepsy because safety,
      accuracy, and efficacy have been well established in both adult and pediatric
      populations. Development of robot-guidance technology has greatly enhanced the
      efficiency of this procedure, without sacrificing safety or precision. To date
      there have been very limited reports of the use of this new technology in
      children. The authors present their initial experience using the ROSA platform
      for robot-guided SEEG in a pediatric population. METHODS Between February 2016
      and October 2017, 20 consecutive patients underwent robot-guided SEEG with the
      ROSA robotic guidance platform as part of ongoing seizure localization and workup
      for medically refractory epilepsy of several different etiologies. Medical and
      surgical history, imaging and trajectory plans, as well as operative records were
      analyzed retrospectively for surgical accuracy, efficiency, safety, and epilepsy
      outcomes. RESULTS A total of 222 leads were placed in 20 patients, with an
      average of 11.1 leads per patient. The mean total case time (+/- SD) was 297.95
      (+/- 52.96) minutes and the mean operating time per lead was 10.98 minutes/lead,
      with improvements in total (33.36 minutes/lead vs 21.76 minutes/lead) and
      operative (13.84 minutes/lead vs 7.06 minutes/lead) case times/lead over the
      course of the study. The mean radial error was 1.75 (+/- 0.94 mm). Clinically
      useful data were obtained from SEEG in 95% of cases, and epilepsy surgery was
      indicated and performed in 95% of patients. In patients who underwent definitive
      epilepsy surgery with at least a 3-month follow-up, 50% achieved an Engel class I
      result (seizure freedom). There were no postoperative complications associated
      with SEEG placement and monitoring. CONCLUSIONS In this study, the authors
      demonstrate that rapid adoption of robot-guided SEEG is possible even at a SEEG
      naive institution, with minimal learning curve. Use of robot guidance for SEEG
      can lead to significantly decreased operating times while maintaining safety, the
      overall goals of identification of epileptogenic zones, and improved epilepsy
      outcomes.

PMID- 30117791
TI  - Overdrainage-related ependymal bands: a postulated cause of proximal shunt
      obstruction.
AB  - OBJECTIVE Ventricular shunts have an unacceptably high failure rate, which
      approaches 50% of patients at 2 years. Most shunt failures are related to
      ventricular catheter obstruction. The literature suggests that obstructions are
      caused by in-growth of choroid plexus and/or reactive cellular aggregation. The
      authors report endoscopic evidence of overdrainage-related ventricular tissue
      protrusions ("ependymal bands") that cause partial or complete obstruction of the
      ventricular catheter. METHODS A retrospective review was completed on patients
      undergoing shunt revision surgery between 2008 and 2015, identifying all cases in
      which the senior author reported endoscopic evidence of ependymal tissue in
      growth into ventricular catheters. Detailed clinical, radiological, and surgical
      findings are described. RESULTS Fifty patients underwent 83 endoscopic shunt
      revision procedures that revealed in-growth of ventricular wall tissue into the
      catheter tip orifices (ependymal bands), producing partial, complete, or
      intermittent shunt obstructions. Endoscopic ventricular explorations revealed
      ependymal bands at various stages of development, which appear to form
      secondarily to siphoning. Ependymal bands are associated with small ventricles
      when the shunt is functional, but may dilate at the time of obstruction.
      CONCLUSIONS Ventricular wall protrusions are a significant cause of proximal
      shunt obstruction, and they appear to be caused by siphoning of surrounding
      tissue into the ventricular catheter orifices.

PMID- 30117790
TI  - Indirect revascularization with the dural inversion technique for pediatric
      moyamoya disease: 20-year experience.
AB  - OBJECTIVE Numerous surgical procedures facilitate revascularization of the
      ischemic brain in patients with moyamoya disease. Dural inversion is a technique
      in which flaps of dura mater centered around the middle meningeal artery are
      inverted, encouraging the formation of a rich collateral blood supply. This
      procedure has been used in combination with encephaloduroarteriosynangiosis for
      more than 20 years at the authors' institution for the treatment of pediatric
      moyamoya disease. The objective of this study was to describe the clinical and
      radiographic outcomes for a cohort of consecutive pediatric moyamoya patients
      undergoing dural inversion. METHODS Clinical and radiographic data on patients
      who had undergone dural inversion in the period from 1997 to 2016 were reviewed.
      Univariate and multivariate logistic regression and Kaplan-Meier analyses were
      performed to assess the risk of postoperative stroke, functional outcome, and the
      angiographic degree of revascularization. RESULTS Dural inversion was performed
      on 169 hemispheres in 102 patients. Median follow-up was 4.3 years. Six patients
      (3.6% of hemispheres) suffered postoperative ischemic or hemorrhagic stroke.
      Overall mortality was 1.0%. Good postoperative neurological status (modified
      Rankin Scale [mRS] score <= 2) was observed in 90 patients (88%); preoperative
      and postoperative mRS scores showed significant improvement (p < 0.001). Eighty
      six percent of hemispheres had Matsushima grade A or B revascularization. Younger
      age was associated with postoperative stroke and poor functional outcome.
      Patients with secondary moyamoya syndrome had a significantly worse radiographic
      outcome. The cumulative 5-year Kaplan-Meier risk for stroke was 6.4%. CONCLUSIONS
      Dural inversion is a useful technique of cerebral revascularization in pediatric
      moyamoya disease. A 20-year experience demonstrates the safety and efficacy of
      this technique with a relatively low rate of postoperative stroke, good
      functional outcomes, and favorable angiographic results.

PMID- 30117792
TI  - Letter to the Editor. Laminotomy outcomes in pediatric patients.

PMID- 30117793
TI  - Perilesional edema associated with an intracranial calcifying pseudoneoplasm of
      the neuraxis in a child: case report and review of imaging features.
AB  - Calcifying pseudoneoplasms of the neuraxis (CAPNONs) are rare, nonneoplastic
      lesions of the CNS. Their radiographic features have been well described, with
      prominent calcifications seen on CT imaging and generally uniform hypointensity
      on T1- and T2-weighted MRI sequences, with variable patterns of contrast
      enhancement. They are not associated with significant perilesional edema. The
      authors present an unusual case of an 8-year-old boy who was found to have a 2.5
      cm right frontal mass that demonstrated reduced signal on T2-weighted sequences,
      heterogeneous contrast enhancement, and extensive perilesional edema on MRI
      sequences. The differential diagnoses included a chronic infection or neoplasm.
      He underwent gross-total resection of a firm, calcified mass that had clear
      boundaries between it and the surrounding gliotic brain. Pathological analysis
      demonstrated a well-circumscribed lesion with islands of lamellar calcifications
      and intervening spindle cells, consistent with a CAPNON. At 8 months after
      surgery the patient remained seizure free, and MRI revealed no evidence of
      residual lesion and significant improvement in perilesional edema. This
      particular case highlights the potential for unusual presentation of CAPNON and
      the rare presence of perilesional edema.

PMID- 30117794
TI  - Letter to the Editor. Pediatric thalamic tumors.

PMID- 30117795
TI  - Randomized trial of Cell Saver in 2- to 3-level lumbar instrumented posterior
      fusions.
AB  - OBJECTIVE The goal of this study was to determine efficacy and cost-effectiveness
      of Cell Saver in 2- and 3-level lumbar decompression and fusion. METHODS Patients
      seen at a tertiary care spine center who were undergoing a posterior 2- or 3
      level lumbar decompression and fusion were randomized to have Cell Saver used
      during their surgery (CS group, n = 48) or not used (No Cell Saver [NCS] group, n
      = 47). Data regarding preoperative and postoperative hemoglobin and hematocrit,
      estimated blood loss, volume of Cell Saver blood reinfused, number of units and
      volume of allogeneic blood transfused intraoperatively and postoperatively,
      complications, and costs were collected. Costs associated with Cell Saver use
      were calculated based on units of allogeneic blood transfusions averted. RESULTS
      Demographics and surgical parameters were similar in both groups. The mean
      estimated blood loss was similar in both groups: 612 ml in the CS group and 742
      ml in the NCS group. There were 53 U of allogeneic blood transfused in 29
      patients in the NCS group at a total blood product cost of $67,688; and 38 U of
      allogeneic blood transfused in 16 patients in the CS group at a total blood cost
      of $113,162, resulting in a cost of $3031 per allogeneic blood transfusion
      averted using Cell Saver. CONCLUSIONS Cell Saver use produced lower rates of
      allogeneic transfusion but was found to be more expensive than using only
      allogeneic blood for 2- and 3-level lumbar degenerative fusions. This increased
      cost may be reasonable to patients who perceive that the risks associated with
      allogeneic transfusions are unacceptable. ? CLASSIFICATION OF EVIDENCE Type of
      question: therapeutic; study design: randomized controlled trial; evidence: class
      III.

PMID- 30117796
TI  - Letter to the Editor. Class imbalance in machine learning for neurosurgical
      outcome prediction: are our models valid?

PMID- 30117797
TI  - Implementation of an Enhanced Recovery After Spine Surgery program at a large
      cancer center: a preliminary analysis.
AB  - OBJECTIVE Enhanced Recovery After Surgery (ERAS) programs follow a multimodal,
      multidisciplinary perioperative care approach that combines evidence-based
      perioperative strategies to accelerate the functional recovery process and
      improve surgical outcomes. Despite increasing evidence that supports the use of
      ERAS programs in gastrointestinal and pelvic surgery, data regarding the
      development of ERAS programs in spine surgery are scarce. To evaluate the impact
      of an Enhanced Recovery After Spine Surgery (ERSS) program in a US academic
      cancer center, the authors introduced such a program and hypothesized that ERSS
      would have a significant influence on meaningful clinical measures of
      postoperative recovery, such as pain management, postoperative length of stay
      (LOS), and complications. METHODS A multimodal, multidisciplinary, continuously
      evolving team approach was used to develop an ERAS program for all patients
      undergoing spine surgery for metastatic tumors at The University of Texas MD
      Anderson Cancer Center from April 2015 through September 2016. This study
      describes the introduction of that ERSS program and compares 41 patients who
      participated in ERSS with a retrospective cohort of 56 patients who underwent
      surgery before implementation of the program. The primary objectives were to
      assess the effect of an ERSS program on immediate postoperative pain scores and
      in-hospital opioid consumption. The secondary objectives included assessing the
      effect of ERSS on postoperative in-hospital LOS, 30-day readmission rates, and 30
      day postoperative complications. RESULTS The ERSS group showed a trend toward
      better pain scores and decreased opioid consumption compared with the pre-ERSS
      group. There were no significant differences in LOS, 30-day readmission rate, or
      30-day complication rate observed between the two groups. RESULTS An ERSS program
      is feasible and potentially effective on perioperative pain control and opioid
      consumption, and can expedite recovery in oncological spine surgery patients.
      Larger-scale research on well-defined postoperative recovery outcomes is needed.

PMID- 30117798
TI  - Genome sequence, metabolic properties and cyanobacterial attachment of
      Porphyrobacter sp. HT-58-2 isolated from a filamentous cyanobacterium-microbial
      consortium.
AB  - Tolyporphins are structurally diverse tetrapyrrole macrocycles produced by the
      cyanobacterial culture HT-58-2. Although tolyporphins were discovered over 25
      years ago, little was known about the microbiology of the culture. The studies
      reported herein expand the description of the community of predominantly
      alphaproteobacteria associated with the filamentous HT-58-2 cyanobacterium and
      isolate a dominant bacterium, Porphyrobacter sp. HT-58-2, for which the complete
      genome is established and growth properties are examined. Fluorescence in situ
      hybridization (FISH) analysis of the cyanobacterium-microbial community with a
      probe targeting the 16S rRNA of Porphyrobacter sp. HT-58-2 showed fluorescence
      emanating from the cyanobacterial sheath. Although genes for the biosynthesis of
      bacteriochlorophyll a (BChl a) are present in the Porphyrobacter sp. HT-58-2
      genome, the pigment was not detected under the conditions examined, implying the
      absence of phototrophic growth. Comparative analysis of four Porphyrobacter spp.
      genomes from worldwide collection sites showed significant collinear gene blocks,
      with two inversions and three deletion regions. Taken together, the results
      enrich our understanding of the HT-58-2 cyanobacterium-microbial culture.

PMID- 30117799
TI  - Acinetobacter wuhouensis sp. nov., isolated from hospital sewage.
AB  - We recovered eight strains of the genus Acinetobacter from hospital sewage at
      West China Hospital in Chengdu, China. Based on the comparative analysis of the
      rpoB sequence, these strains formed a strongly supported and internally coherent
      cluster (intra-cluster identity of >=98.0 %), which was clearly separated from
      all known Acinetobacter species (<=91.1 %). The eight strains also formed a tight
      and distinct cluster based on the genus-wide comparison of whole-cell mass
      fingerprints generated by matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry. In addition, the combination of their ability to
      assimilate 2,3-butanediol and phenylacetate, but not 4-hydroxybenzoate, and the
      inability to grow at 37  degrees C could distinguish these eight strains from all
      known Acinetobacter species. Whole-genomic sequencing has been performed for two
      selected strains, WCHA60T and WCHA62. There were 96.65 % average nucleotide
      identity (ANI) and 72 % in silico DNA-DNA hybridization (isDDH) values between
      WCHA60T and WCHA62, suggesting that the two strains indeed belonged to the same
      species. In contrast, the ANI and isDDH values between the two strains and the
      known Acinetobacter species were <83 and <30 %, respectively; both of which were
      far below the cut-off to define a bacterial species. Therefore, the eight strains
      should be considered to represent a novel species of the genus Acinetobacter, for
      which the name Acinetobacterwuhouensis sp. nov. is proposed. The type strain is
      WCHA60T (=CCTCC AB 2016204T=GDMCC 1.1100T=KCTC 52505T).

PMID- 30117800
TI  - Lactobacillus porci sp. nov., isolated from small intestine of a swine.
AB  - A facultatively anaerobic, Gram-stain-positive, catalase-negative, rod-shaped
      lactic acid bacterium, designated SG816T, was isolated from small intestine of a
      swine. Optimal growth occurred at 37  degrees C and pH 7.0. Furthermore, growth
      occurred in NaCl up to 0.5 % (w/v) but not at levels of salinity higher than 1 %.
      Comparative 16S rRNA gene sequencing and the matrix-associated laser
      desorption/ionization-time-of-flight mass spectometry profiling showed that
      strain SG816T was closely related to Lactobacillus delbrueckiisubsp. bulgaricus
      KCTC 3635T (95.9 %) and Lactobacillus delbrueckiisubsp. indicus JCM 15610T (95.9
      %), followed by other Lactobacillus delbrueckii subspecies (95.9-95.7 %) and
      Lactobacillus equicursoris DSM 19284T (95.6 %). A comparison of two housekeeping
      genes, RNA polymerase alpha subunit (rpoA) and phenylalanyl-tRNA synthase alpha
      subunit (pheS), revealed that strain SG816T formed a separate branch within the
      clade of the genus Lactobacillus. The DNA G+C content level of the strain SG816T
      was 51.5 mol%. The strain was homofermentative and produced d-lactic acid from
      glucose fermentation. The major cellular fatty acids (>10 %) of the isolate were
      C18 : 1omega9c and C16 : 0. The peptidoglycan type was A4alpha l-Lys-d-Asp. On
      the basis of distinct phenotypic and phylogenetic properties, strain SG816T
      represents a novel species of the genus Lactobacillus, for which the name
      Lactobacillus porci sp. nov. is proposed. The type strain is SG816T (=KCTC
      21090T=NBRC 112917T).

PMID- 30117801
TI  - Motiliproteus coralliicola sp. nov., a bacterium isolated from coral.
AB  - A Gram-stain-negative, non-spore-forming, aerobic, motile, ovoid or rod-shaped
      bacterium, designated strain C34T, was isolated from a Porites species coral on
      Weizhou Island, China. Optimal growth occurred in 4 % NaCl (w/v), at 30  degrees
      C and pH 8. The only detected respiratory quinone was Q-8. The major polar lipids
      were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two
      unidentified ninhydrin-positive lipids, one ninhydrin-positive unidentified
      phospholipid and two unidentified polar lipids. The genome DNA G+C content was
      56.7 mol%. The major cellular fatty acids were C16 : 1omega7c/iso-C15 : 0 2-OH,
      C16 : 0, C18 : 1omega7c/omega6c, C18 : 0 and iso-C11 : 0 3-OH. Phylogenetic
      analyses based on 16S rRNA gene sequences indicated that strain C34T forms a
      stable cluster with Motiliproteus sediminis CICC 10858T (with the highest
      sequence similarity of 95.7 %). Strain C34T was also physiologically and chemical
      taxonomically similar to M. sediminis CICC 10858T, although they could be
      distinguished by colony colour on 2216E agar, the flagellum position and the
      diphosphatidylglycerol content in the cellular polar lipid. Thus, strain C34T is
      suggested to represent a new species in the genus Motiliproteus, for which the
      name Motiliproteus coralliicola is proposed. The type strain is C34T (=MCCC
      1K03462T=KCTC 62319T).

PMID- 30117802
TI  - Prevalence of Sodalis glossinidius and different trypanosome species in Glossina
      palpalis palpalis caught in the Fontem sleeping sickness focus of the southern
      Cameroon.
AB  - Tsetse flies are the cyclical vector of human and animal African trypanosomiasis.
      To improve vector control in order to achieve the elimination of human African
      trypanosomiasis (HAT) and boost the control of animal diseases, investigations
      have been undertaken on the tripartite association between tsetse, trypanosome,
      and symbionts. It is in this light that Sodalis glossinidius and different
      trypanosomes were identified in Glossina palpalis palpalis caught in Fontem in
      southern Cameroon. For this study, DNA was extracted from whole flies, and S.
      glossinidius and different trypanosome species were identified by polymerase
      chain reaction (PCR). Statistical analyses were performed to compare the
      trypanosome and S. glossinidius infection rates and to look for an association
      between these microorganisms. Of the 274 G. p. palpalis caught, 3.3% (9/274) were
      teneral. About 35% (96/274) of these flies harbored S. glossinidius. Of the 265
      non-teneral flies, 37.7% were infected by trypanosomes. The infection rates of
      Trypanosoma congolense "forest type" and Trypanosoma vivax were 26.04% and
      18.11%, respectively. About 6.41% of tsetse harbored mixed infections of T.
      congolense and T. vivax. Of the 69 tsetse with T. congolense infections, 33.33%
      (23/69) harbored S. glossinidius while 71.86% (69/96) of flies harboring S.
      glossinidius were not infected by trypanosomes. No association was observed
      between S. glossinidius and trypanosome infections. Some wild tsetse harbor S.
      glossinidius and trypanosomes, while others have no infection or are infected by
      only one of these microorganisms. We conclude that the presence of S.
      glossinidius does not favor trypanosome infections in G. p. palpalis of the
      Fontem focus.

PMID- 30117804
TI  - MAPLE (modular automated platform for large-scale experiments), a robot for
      integrated organism-handling and phenotyping.
AB  - Lab organisms are valuable in part because of large-scale experiments like
      screens, but performing such experiments over long time periods by hand is
      arduous and error-prone. Organism-handling robots could revolutionize large-scale
      experiments in the way that liquid-handling robots accelerated molecular biology.
      We developed a modular automated platform for large-scale experiments (MAPLE), an
      organism-handling robot capable of conducting lab tasks and experiments, and then
      deployed it to conduct common experiments in Saccharomyces cerevisiae,
      Caenorhabditis elegans, Physarum polycephalum, Bombus impatiens, and Drosophila
      melanogaster. Focusing on fruit flies, we developed a suite of experimental
      modules that permitted the automated collection of virgin females and execution
      of an intricate and laborious social behavior experiment. We discovered that (1)
      pairs of flies exhibit persistent idiosyncrasies in social behavior, which (2)
      require olfaction and vision, and (3) social interaction network structure is
      stable over days. These diverse examples demonstrate MAPLE's versatility for
      automating experimental biology.

PMID- 30117803
TI  - An assay for de novo kinetochore assembly reveals a key role for the CENP-T
      pathway in budding yeast.
AB  - Chromosome segregation depends on the kinetochore, the machine that establishes
      force-bearing attachments between DNA and spindle microtubules. Kinetochores are
      formed every cell cycle via a highly regulated process that requires coordinated
      assembly of multiple subcomplexes on specialized chromatin. To elucidate the
      underlying mechanisms, we developed an assay to assemble kinetochores de novo
      using centromeric DNA and budding yeast extracts. Assembly is enhanced by mitotic
      phosphorylation of the Dsn1 kinetochore protein and generates kinetochores
      capable of binding microtubules. We used this assay to investigate why
      kinetochores recruit the microtubule-binding Ndc80 complex via two receptors: the
      Mis12 complex and CENP-T. Although the CENP-T pathway is non-essential in yeast,
      we demonstrate that it becomes essential for viability and Ndc80c recruitment
      when the Mis12 pathway is crippled by defects in Dsn1 phosphorylation. Assembling
      kinetochores de novo in yeast extracts provides a powerful and genetically
      tractable method to elucidate critical regulatory events in the future.

PMID- 30117805
TI  - A cell autonomous torsinA requirement for cholinergic neuron survival and motor
      control.
AB  - Cholinergic dysfunction is strongly implicated in dystonia pathophysiology.
      Previously (Pappas et al., 2015;4:e08352), we reported that Dlx5/6-Cre mediated
      forebrain deletion of the DYT1 dystonia protein torsinA (Dlx-CKO) causes abnormal
      twisting and selective degeneration of dorsal striatal cholinergic interneurons
      (ChI) (Pappas et al., 2015). A central question raised by that work is whether
      the ChI loss is cell autonomous or requires torsinA loss from neurons
      synaptically connected to ChIs. Here, we addressed this question by using ChAT
      Cre mice to conditionally delete torsinA from cholinergic neurons ('ChAT-CKO').
      ChAT-CKO mice phenocopy the Dlx-CKO phenotype of selective dorsal striatal ChI
      loss and identify an essential requirement for torsinA in brainstem and spinal
      cholinergic neurons. ChAT-CKO mice are tremulous, weak, and exhibit trunk
      twisting and postural abnormalities. These findings are the first to demonstrate
      a cell autonomous requirement for torsinA in specific populations of cholinergic
      neurons, strengthening the connection between torsinA, cholinergic dysfunction
      and dystonia pathophysiology.

PMID- 30117806
TI  - Inhibition gates supralinear Ca2+ signaling in Purkinje cell dendrites during
      practiced movements.
AB  - Motor learning involves neural circuit modifications in the cerebellar cortex,
      likely through re-weighting of parallel fiber inputs onto Purkinje cells (PCs).
      Climbing fibers instruct these synaptic modifications when they excite PCs in
      conjunction with parallel fiber activity, a pairing that enhances climbing fiber
      evoked Ca2+ signaling in PC dendrites. In vivo, climbing fibers spike
      continuously, including during movements when parallel fibers are simultaneously
      conveying sensorimotor information to PCs. Whether parallel fiber activity
      enhances climbing fiber Ca2+ signaling during motor behaviors is unknown. In
      mice, we found that inhibitory molecular layer interneurons (MLIs), activated by
      parallel fibers during practiced movements, suppressed parallel fiber enhancement
      of climbing fiber Ca2+ signaling in PCs. Similar results were obtained in acute
      slices for brief parallel fiber stimuli. Interestingly, more prolonged parallel
      fiber excitation revealed latent supralinear Ca2+ signaling. Therefore, the
      balance of parallel fiber and MLI input onto PCs regulates concomitant climbing
      fiber Ca2+ signaling.

PMID- 30117809
TI  - Numerical relativity of compact binaries in the 21st century.
AB  - We review the dramatic progress in the simulations of compact objects and compact
      object binaries that has taken place in the first two decades of the twenty-first
      century. This includes simulations of the inspirals and violent mergers of
      binaries containing black holes and neutron stars, as well as simulations of
      black-hole formation through failed supernovae and high-mass neutron star-neutron
      star mergers. Modeling such events requires numerical integration of the field
      equations of general relativity in three spatial dimensions, coupled, in the case
      of neutron-star containing binaries, with increasingly sophisticated treatment of
      fluids, electromagnetic fields, and neutrino radiation. However, it was not until
      2005 that accurate long-term evolutions of binaries containing black holes were
      even possible (Pretorius 2005 Phys. Rev. Lett. 95 121101, Campanelli et al 2006
      Phys. Rev. Lett. 96 111101, Baker et al 2006 Phys. Rev. Lett. 96 111102). Since
      then, there has been an explosion of new results and insights into the physics of
      strongly-gravitating system. Particular emphasis has been placed on understanding
      the gravitational wave and electromagnetic signatures from these extreme events.
      And with the recent dramatic discoveries of gravitational waves from merging
      black holes by the Laser Interferometric Gravitational Wave Observatory and
      Virgo, and the subsequent discovery of both electromagnetic and gravitational
      wave signals from a merging neutron star-neutron star binary, numerical
      relativity became an indispensable tool for the new field of multimessenger
      astronomy.

PMID- 30117807
TI  - Ordered arrangement of dendrites within a C. elegans sensory nerve bundle.
AB  - Biological systems are organized into well-ordered structures and can evolve new
      patterns when perturbed. To identify principles underlying biological order, we
      turned to C. elegans for its simple anatomy and powerful genetics. We developed a
      method to quantify the arrangement of three dendrites in the main sensory nerve
      bundle, and found that they exhibit a stereotyped arrangement throughout larval
      growth. Dendrite order does not require prominent features including sensory
      cilia and glial junctions. In contrast, loss of the cell adhesion molecule (CAM)
      CDH-4/Fat-like cadherin causes dendrites to be ordered randomly, despite
      remaining bundled. Loss of the CAMs PTP-3/LAR or SAX-7/L1CAM causes dendrites to
      adopt an altered order, which becomes increasingly random as animals grow.
      Misexpression of SAX-7 leads to subtle but reproducible changes in dendrite
      order. Our results suggest that combinations of CAMs allow dendrites to self
      organize into a stereotyped arrangement and can produce altered patterns when
      perturbed.

PMID- 30117810
TI  - How surfactant-decorated nanoparticles contribute to thermodynamic miscibility.
AB  - In this study, mineral oil-water fluid miscibility without and with the addition
      of surfactant-decorated nanoparticles is experimentally and theoretically
      studied. First, three series of interfacial tension (IFT) tests are conducted
      using a spinning drop tensiometer (SDT) with the addition of
      hexadecyltrimethylammonium bromide (CTAB) surfactant-decorated SiO2 nanoparticles
      at different concentrations. Second, a new comprehensive thermodynamic model is
      developed to describe the fluid miscibility without and with the addition of
      these surfactant-decorated nanoparticles, which is also applied theoretically to
      reveal how the surfactant-decorated nanoparticles contribute to the thermodynamic
      miscibility state. The thermodynamic model developed is proven to be accurate and
      physically meaningful by comparing its calculated free energy of mixing with the
      experimental results and examples from the literature. A series of optimum
      conditions for the improvement of fluid miscibility by the addition of such
      surfactant-decorated nanoparticles are determined: a lower temperature, a higher
      pressure, more wetting conditions, a smaller nanoparticle radius (r NP < 40 nm),
      a larger surfactant concentration, and a nanoparticle concentration in the range
      of 0.5-0.6 wt.%. It should be noted that a higher nanoparticle concentration is
      required with the addition of more CTAB surfactants in order to reach the most
      miscible state. Moreover, the effect of surfactant concentration on the
      miscibility development is found to be independent of the nanoparticle radius,
      whereas the optimum nanoparticle concentration is reduced with increasing
      particle size.

PMID- 30117811
TI  - Prediction of obstructive sleep apnea using facial landmarks.
AB  - : The collapsibility of the upper airway has a known anatomical basis that is
      mediated by an interaction of obesity and craniofacial abnormalities. The pattern
      of these abnormalities, if detected in a subject's facial image, can help predict
      the presence of obstructive sleep apnea (OSA). OBJECTIVE: We utilized facial
      photographs (front and profile) from 376 patients who had undergone an overnight
      polysomnogram to identify those with and without OSA. Approach (i): Processing
      the images had three steps: landmark identification, feature generation, and
      automatic classification. Firstly, we used unaligned landmarks and investigated
      the impact of manually and automatically determined landmarks on the performance
      of the classification algorithms. Main results (i): Using a feature set
      calculated from manually determined landmarks ('constrained features') we
      obtained 67.0% accuracy in identifying OSA (AHI  >  10) and using automatically
      determined landmarks we obtained 65.5% accuracy for OSA. Approach (ii): Secondly,
      we aligned the facial landmark coordinates by using an image registration
      technique utilising linear transformations. Main results (ii): Directly using the
      aligned landmark coordinates ('unconstrained features') by the classification
      stage as the new feature set resulted in an accuracy of 69.7% in OSA detection
      using manually determined landmarks and 69.2% using automatically determined
      landmarks. SIGNIFICANCE: The performance of our fully automatic system using the
      unconstrained feature set is comparable to other published systems requiring a
      manual landmarking process. In conclusion, we demonstrate the feasibility of
      using automatic landmarking as well as unconstrained features in the successful
      prediction of OSA using facial landmarks.

PMID- 30117808
TI  - Fizzy-Related dictates A cell cycle switch during organ repair and tissue growth
      responses in the Drosophila hindgut.
AB  - Ploidy-increasing cell cycles drive tissue growth in many developing organs. Such
      cycles, including endocycles, are increasingly appreciated to drive tissue growth
      following injury or activated growth signaling in mature organs. In these organs,
      the regulation and distinct roles of different cell cycles remains unclear. Here,
      we uncover a programmed switch between cell cycles in the Drosophila hindgut
      pylorus. Using an acute injury model, we identify mitosis as the response in
      larval pyloric cells, whereas endocycles occur in adult pyloric cells. By
      developing a novel genetic method, DEMISE (Dual-Expression-Method-for-Induced
      Site-specific-Eradication), we show the cell cycle regulator Fizzy-related
      dictates the decision between mitosis and endocycles. After injury, both cycles
      accurately restore tissue mass and genome content. However, in response to
      sustained growth signaling, only endocycles preserve epithelial architecture. Our
      data reveal distinct cell cycle programming in response to similar stimuli in
      mature vs. developmental states and reveal a tissue-protective role of
      endocycles.

PMID- 30117812
TI  - Band optimization of passive methane gas leak detection based on uncooled
      infrared focal plane array: publisher's note.
AB  - This publisher's note amends the author listing in Appl. Opt.57, 3991
      (2018)APOPAI0003-693510.1364/AO.57.003991.

PMID- 30117813
TI  - Optical characterization of Chinese hybrid rice using laser-induced fluorescence
      techniques-laboratory and remote-sensing measurements: publisher's note.
AB  - This publisher's note corrects the author listing and a figure caption in Appl.
      Opt.57, 3481 (2018)APOPAI0003-693510.1364/AO.57.003481.

PMID- 30117814
TI  - D-shaped photonic crystal fiber plasmonic refractive index sensor based on gold
      grating.
AB  - In this work, we proposed a high-resolution D-shaped photonic crystal fiber (PCF)
      surface plasmon resonance (SPR) sensor based on gold grating. Gold grating is
      introduced to modulate the resonance wavelength and enhance the refractive index
      (RI) sensitivity. Structure parameters of PCF and gold grating are analyzed by
      the finite element method for optimizing the SPR sensor. The simulation results
      indicate that air hole pitch, air hole diameter, and gold thickness and grating
      constant have little influence on the sensitivity of the refractive index, which
      reduces the requirement of precise processing. For improving the resolution of RI
      sensing, a two-feature (2F) interrogation method, which combines wavelength
      interrogation and amplitude interrogation, is used. The maximum theoretical
      resolution of the SPR sensor reaches to 5.98*10-6  RIU in the range of 1.36-1.38,
      and the wavelength sensitivity reaches to 3340 nm/RIU. The proposed SPR sensor
      shows potential applications for developing a high-sensitivity, real-time, and
      fast-response SPR-RI sensor.

PMID- 30117815
TI  - Chromatic analysis of harmonic Fresnel lenses by FDTD and angular spectrum
      methods.
AB  - In this paper, we present a detailed and rigorous study of cylindrical harmonic
      Fresnel lenses (HFLs) using the finite difference time domain method (FDTD) and
      angular spectrum method (ASM). The HFL is a kind of diffractive lens that can
      have maximum diffraction efficiency at several discrete harmonic wavelengths,
      which is suitable for some broadband applications. Previous studies on HFLs were
      investigated mainly in the domain of paraxial approximation. By using our
      proposed calculation method, we have determined the efficiency, focal length,
      maximum focus intensity, and full width at half maximum (FWHM) of the focal spot
      for several harmonic numbers and for F-numbers of 0.5, 1, and 3. To compare with
      the paraxial approximation, we have presented the response to both s-polarized
      and p-polarized light with constant refractive index and real dispersive
      material, BK7. Moreover, we have also analyzed the cases with oblique
      illumination. We have shown that the harmonic wavelengths do not change with F/#
      and that the diffraction efficiency and FWHM of the focus increase as F/#
      increases. New results on harmonic wavelengths shift and oblique angle of
      incidence response have been detailed.

PMID- 30117816
TI  - Optical camera communication for mobile payments using an LED panel light.
AB  - As mobile payments become increasingly popular, the security of the transaction
      process should be taken more seriously. Many mobile phones are equipped with
      complementary metal-oxide-semiconductor (CMOS) cameras, which can be used as
      visible light communication (VLC) receivers. An optical camera communication
      (OCC) system is a special VLC system that uses an optical camera as a receiver.
      OCC offers acceptable security, but challenges remain. In this paper, we propose
      an OCC system that uses an optical camera with a rolling shutter as a receiver
      and a light-emitting diode (LED) panel light as a transmitter. The feature of an
      LED panel light serving as a surface light source reduces the possibility of
      overexposure and avoids the blooming effect of the camera. The rolling shutter
      effect of the CMOS camera is used to increase the data rate, which is numerically
      much higher than the frame rate. Finally, the results of a symbol error rate
      (SER) test show that the VLC system exhibits error-free performance. The data
      rate is approximately 4.2 kb/s, while the net data rate is approximately 2.46
      kb/s due to the redundancy of the 3-9 code bar code and the redundant cycle. This
      data rate is sufficient for mobile payments, which require only 60 bits of data
      at a time.

PMID- 30117817
TI  - PCSEL pumped coupling optics free Yb:YAG/Cr:YAG microchip laser.
AB  - The passively Q-switched operation of a cryogenically cooled Yb:YAG/Cr:YAG
      microchip laser was demonstrated with end pumping by a photonic crystal surface
      emitting laser (PCSEL). This laser generated 70 MUJ/1.7 ns/3.2 kHz pulses with
      near diffraction limited beam quality (M2=1.1) at 1029.4 nm. There were no
      coupling optics between the microchip laser crystal and PCSEL, which made the
      system simple and compact.

PMID- 30117818
TI  - Resonance-domain diffractive microlens arrays.
AB  - High-efficiency resonance-domain diffractive microlens arrays with high numerical
      apertures and 100% fill factor were designed, fabricated, and characterized.
      Fabricated arrays of eight off-axis microlenses with pitch 127 MUm and numerical
      aperture 0.2 demonstrated diffraction-limited collimation of fiber light at 632.8
      nm wavelength. Optical measurements revealed diffraction efficiency exceeding
      93%, in match to numerical calculations with rigorous conical diffraction. The
      resonance-domain diffractive microlens arrays are highly suitable for
      applications in fiber optics, multispot optical tweezers, optical sensors, and
      spectrometry.

PMID- 30117819
TI  - Multispot launching for single-mode excitation in multimode fibers for high-speed
      applications.
AB  - Several launching methods have been employed in multimode fibers (MMFs) to reduce
      the intermodal dispersion. Selective excitation of the fundamental mode alone in
      an MMF can eliminate intermodal dispersion completely, provided the mode coupling
      along the fiber is minimum. In this paper, we present the design of a two-core
      fiber taper that results in the generation of a mode-field diameter-matched twin
      spot beam, which can effectively excite only the fundamental mode (LP01) in an
      MMF. We also propose a new launching method, viz. dual twin-spot launching, which
      excites the LP01 mode alone in an MMF for a wide range of input beam spot sizes
      as compared to the other existing methods. The design of a four-core fiber taper
      for generating the proposed dual twin-spot beam is also presented. Misalignment
      tolerance of the dual twin-spot beam launching is compared with mode-field
      diameter-matched center launch (MFDM-CL) and mode-field diameter-matched twin
      spot launch (MFDM-TSL). We show that the dual twin-spot launching method has
      higher alignment tolerances.

PMID- 30117820
TI  - Phase-stable, downconverting, microwave photonic link with analysis of balanced
      heterodyne detection intermodulation.
AB  - A coherent downconverting microwave photonic link using balanced heterodyne
      detection of single-sideband modulated optical signals is analyzed and
      demonstrated. The intermodulation analysis shows that the second-order
      photodetector nonlinearity can be the limiting factor in the third-order
      intermodulation spur performance. The link is designed to phase coherently
      downconvert 17 GHz of bandwidth in an extended K-band (23-45 GHz) to 1-18 GHz to
      match the capabilities of modern receivers. The application of the link is for a
      low-loss >20  MUs analog buffer. Spur performance of 112.4  dB/Hz(2/3) is
      demonstrated when background noise is limited by shot noise.

PMID- 30117821
TI  - Wine glass caustic and halo analogies.
AB  - This paper aims to develop an understanding of a peculiar hourglass-shaped
      caustic that can be observed if a partially filled wine glass is illuminated by
      parallel light. The light pattern is first described in terms of an idealized
      model of the liquid volume only: the sum of the parametric projection curves
      obtained by light refraction through liquid cones of varying wall inclinations in
      the framework of geometrical optics. Within this analysis, analogues to two
      specific refraction ice halos, the circumzenithal and the Parry arc, will prove
      to be helpful. The analysis is supplemented by ray tracing simulations that
      further elucidate the origin of the hourglass caustic when the glass is added to
      the refraction scenario.

PMID- 30117822
TI  - Q-Spectrum and its application for the characterization of mid-spatial
      frequencies on polished surfaces.
AB  - The current paper reports on the application of the Q-Spectrum for the
      characterization of mid-spatial frequencies on polished surfaces (plane,
      spherical, and aspheres). The Q-Spectrum based on the Forbes Qmn polynomials for
      freeforms allows, when taken to large radial and azimuthal orders, a robust and
      accurate representation of mid-spatial surface spectral footprints that otherwise
      cannot be faithfully identified with other methods. Evaluation of experimental
      data with the Q-Spectrum as well as a comparison with other methods is shown.

PMID- 30117823
TI  - Simulation of optical fiber couplers using the angular spectrum algorithm.
AB  - We examine single-mode optical fiber transmission using the angular spectrum
      method. We find excellent agreement with the theoretical solutions for the
      cylindrical single-mode optical fiber. Next, we examine fiber coupler
      configurations with 1*2, 1*3, and 1*5 designs. The input within the central fiber
      core is broadcast equally into the surrounding fiber cores and then returns with
      propagation distances as expected. Then we examine supermode theory for the 1*3
      case. The initial energy is sent into different combinations of fiber cores where
      their phase relationship governs the output. Surprisingly, we find evidence of an
      unexpected mode in some of the multicore designs. We expect these results might
      be useful for exploration of more complicated fiber core arrays. However,
      computational times are short using this algorithm.

PMID- 30117824
TI  - Plasmonic nano-tweezer based on square nanoplate tetramers.
AB  - The research fields of trapping nanoparticles have experienced a huge development
      in recent years, which mainly benefits from the unique field enhancement in
      plasmonic nanomaterials. Since the large field enhancement originates from the
      excited localized surface plasmon at the metal surface, exploring novel metal
      nanostructures with high trapping efficiency is always the main goal in this
      field. In this work, the plasmonic trapping of nanoparticles based on the gold
      periodic square tetramers (PST) was investigated through full-wave simulations
      using the finite-difference time-domain (FDTD) method. The electric field and
      surface charge distributions on the surface of PST indicate that both the
      trapping position and efficiency are influenced by orientations of the square
      nanoplates. The maximum electromagnetic enhancement is achieved when all square
      nanoplates rotate 45 degrees  along the z axis. Therefore, the gradient force and
      trapping potential of this PST with optimal orientation were further studied, and
      the results indicate that a dielectric nanoparticle of 15 nm radius can be stably
      captured. Furthermore, the calculation results show that the plasmonic trapping
      with this PST exhibits strong polarization dependence. It is easy to change the
      trapping position and the field intensity by tuning the polarization of the
      incident wave. Our work enables a deeper understanding of this kind of plasmonic
      trapping and could have potential applications in biomedical research and life
      science.

PMID- 30117825
TI  - On a causal dispersion model for the optical properties of metals.
AB  - A causal model that is fully compliant with the Kramers-Kronig relations (KKRs)
      is used for characterizing the optical response of metals exhibiting sharp, non
      Lorentzian regions of interband absorption. This consistent model also recovers
      the Gaussian character of the broadened peaks observed in the infrared response
      of amorphous materials. A reductive procedure for optimal fitting of KKR
      compliant composite models to the permittivity data of metals over the intraband
      and interband energetic regimes is introduced and applied to eleven metals: Ag,
      Au, Cu, Al, Be, Cr, Ni, Pd, Pt, Ti, and W. We show that results obtained using
      this optimal procedure outperform-both qualitatively and quantitatively-those
      obtained by previous non-causal (KKR non-compliant) models that are widely used
      for approximating the permittivity of metals. A comparative analysis reveals a
      simultaneous increase in performance (as characterized by the error objective)
      and a reduction in the cardinality of the parameterization, often yielding more
      physically meaningful interpretations. These results are obtained without
      compromising model fidelity in regions of sharp Gaussian interband character,
      indicating that the proposed model provides an excellent alternative to
      previously proposed models.

PMID- 30117826
TI  - Enhanced light trapping in thin-film silicon solar cells with concave quadratic
      bottom gratings.
AB  - We present a theoretical crystalline silicon thin-film solar cell with concave
      quadratic bottom gratings using parametric design of the gratings and
      systematically perform optoelectronic simulations of the proposed grating
      structures. Numerical results reveal that the concave quadratic grating structure
      leads to a desirable enhancement of light absorption in the near-IR region (750
      1100 nm), and this enhancement is dominated by TE-polarized light. The mechanisms
      of light absorption enhancement under TE-polarized light are based on the hybrid
      effect of optical waveguide modes and Fabry-Perot modes. Moreover, research
      results indicate that the concave quadratic grating structure has excellent light
      focusing effects, which is conducive to the excitation of optical waveguide
      modes. The study findings can be utilized to improve the efficiency of thin-film
      solar cells based on grating structures.

PMID- 30117827
TI  - Statistics of normalized Stokes polarization parameters.
AB  - The normalized Stokes parameters are formed from the ratio of the polarization
      components to the intensity component of light. Such ratio distributions are
      known to have an undefined mean and variance, and yet researchers in the
      polarization community work with these normalized parameters all the time. We
      show that while in theory the normalized parameters have a pathological
      probability density, in practice they are quite well-behaved. We provide
      expressions for their approximate densities and confirm the results with
      laboratory measurements.

PMID- 30117828
TI  - Coherent noise reduction of phase images in digital holographic microscopy based
      on the adaptive anisotropic diffusion.
AB  - The suppression of coherent noise can produce higher-quality reconstructed images
      in digital holographic microscopy. A robust and effective phase coherent noise
      denoising algorithm is proposed in this paper that combines the anisotropic
      diffusion equation and the phase quality map. In order to accurately identify the
      noise and signal pixels, we introduce the phase quality map and edge detection to
      quantify the quality of the pixel information. In addition, a synthetic diffusion
      function is established to control the speed of the anisotropic diffusion process
      based on the quality coefficient. Several experiments have been carried out to
      validate the effectiveness of the proposed algorithm for coherent noise
      reduction. The results demonstrate that the proposed algorithm can reduce
      coherent noise and preserve edge details well.

PMID- 30117829
TI  - Three-dimensional measurement of an inner surface profile using a supercontinuum
      beam.
AB  - We demonstrate an inner surface profile measurement that has a smooth spatial
      distribution. A supercontinuum beam suppresses the speckle contrast to 22% and
      the standard deviation of the point cloud to 40%, compared to equivalent values
      obtained by use of a conventional green He-Ne laser at a wavelength of 543.5 nm.
      A compact probe for the inner surface profile measurements using the
      supercontinuum beam measures the depth removed by wear of a small hole in an
      automobile component. The radial spatial resolution was evaluated to be 2 MUm,
      which was of the same order as the wavelength of the supercontinuum beam. The
      supercontinuum beam enables fivefold improvement of the radial spatial resolution
      compared to the monochromatic wavelength beam because of a reduction in speckle
      effects.

PMID- 30117830
TI  - Enhanced mid-infrared emission of erbium-doped fluoro-bromozirconate glass.
AB  - A series of erbium-doped fluoro-bromozirconate glasses modified by various
      concentrations of Br- was prepared using the melt-quenching method. The mid
      infrared fluorescence intensity (2.7 MUm) was improved by increasing the content
      of Br-. The differential scanning calorimetry, x-ray diffraction, Fourier
      transform infrared spectra, Raman spectra, and mid-infrared luminescence spectra
      were measured. The decreased phonon density shows that the structural changes due
      to inserting Br- can enhance the mid-infrared luminescent intensity. From the
      Judd-Ofelt analysis, it was found that the intensity of Omega2 was enhanced with
      the introduction of Br- and shows greater asymmetry and stronger covalency. Using
      the Fuchtbauer-Ladenburg theory and McCumber theory, the emission cross section
      (2.9*10-20  cm2) and absorption cross section (1.68*10-20  cm2) at 2.7 MUm were
      determined. Hence, erbium-doped fluoro-bromozirconate glass is a potential
      material for application in the mid-infrared region.

PMID- 30117831
TI  - Measurement of thermal effects of diode-pumped solid-state laser by using digital
      holography.
AB  - Thermal lensing is one of the most important factors that can affect the
      performance of high-power solid-state lasers, such as limiting the power scaling
      capability and deteriorating output beam quality. In this paper, a novel and
      accurate measurement of digital holography is proposed to determine the thermal
      lensing of diode-pumped solid-state lasers with high resolution. The digitally
      recorded hologram can reveal the phase change when light travels through the
      laser gain medium. From the phase map, we can obtain the index variations induced
      by temperature differences inside the laser crystal when it is pumped by laser
      diodes, as well as determine the focal length of the integrated thermal lensing
      focus length. There was much work on measuring the static laser medium thermal
      lens because there is no laser output from the cavity in the setup. Our
      experiment setup was able to achieve online measurement with laser output at the
      same time. The measuring result can provide an accurate guide for compensating
      the thermal lensing in laser design to achieve high-power output and good beam
      quality. Moreover, detailed index variations in the direction of the laser
      crystal cross-section can be numerically reconstructed, by which the thermal
      effects, pump uniformity, crystal uniformity, etc., can be revealed from the
      holography result.

PMID- 30117832
TI  - 3D imaging scanner.
AB  - This paper proposes a multi-view three-dimensional display method based on a
      scanning imaging system with the light-intensity characteristic recorded by an
      improved flatbed scanner. Within the effective scanning depth of the imaging
      sensor, two transmission images are each simultaneously acquired by two linear
      CCD modules with different focal planes. Then the phase gradient information of
      the target can be obtained by an appropriate retrieval algorithm. Further, the
      multi-view three-dimensional effect is presented through dynamic angles of view.
      Theoretical analysis of this method is discussed, and experiments are carried out
      by building a scanner. The experiment results are presented with an algae
      specimen and transparent beads. We hope this method can be applied to present the
      three-dimensional effect of objects of flat translucent multilayer structure with
      a wide field of view.

PMID- 30117833
TI  - Multiple wavelength-selecting and beam-splitting photonic crystal functional
      device based on the mode coupling between the central microcavity and the
      adjacent waveguides.
AB  - The beam-splitting and wavelength selecting characteristics of the two
      dimensional square-lattice photonic crystal with a rectangular microcavity and
      adjacent W1-type waveguides are studied. Based on the abundant defective modes
      with different symmetries supported by the central microcavity, a multiple
      functional device with the abilities of beam splitting and wavelength selecting
      is achieved. Through altering the connecting location between the input/output
      channels and the central microcavity, the proposed device can achieve three kinds
      of functions at different wavelengths within an ultra-small wavelength band of
      about 3 nm, a maximum transmittance of 0.57, and signal-to-noise ratio of 149 are
      achieved for the one-channel selecting, 0.31 and 146 for two-channel splitting,
      and a maximum transmittance of 0.24 for the three-channel light beam sharing. The
      corresponding forward directions of light propagation along the output channels
      can also be flexibly adjusted.

PMID- 30117834
TI  - Imaging method based on the combination of microlens arrays and aperture arrays.
AB  - Conventional imaging methods will cause a serious distortion for large object
      plane imaging with a limited object-to-sensor distance (OTSD). Here, we propose
      an imaging method based on the combination of microlens arrays and aperture
      arrays to realize the low-distortion, large object plane imaging range (OPIR) and
      compact design imaging at a close OTSD. Two-stage microlens arrays are utilized
      to reduce the distance between the object and sensor with low distortion, and two
      stage aperture arrays are sandwiched between the microlens arrays to eliminate
      stray light between different microlenses. The theoretical analysis and
      simulation results indicate that our proposed method can realize low-distortion
      imaging with a large OPIR when the OTSD is seriously limited. This imaging method
      can be used widely in small-size optical devices where the OTSD is extremely
      limited.

PMID- 30117835
TI  - Annular waveguide lasers at 1064  nm in Nd:YAG crystal produced by femtosecond
      laser inscription.
AB  - We report on the fabrication of annular cladding waveguides in Nd:YAG laser
      crystal by using femtosecond laser inscription. The circular cross sections of
      the optical waveguides were in dual-cladding and tri-cladding shapes with
      different diameters. Under the optical pump at 808 nm, the generated continuous
      wave lasers at 1064 nm have been realized in the annular cladding waveguides. For
      dual-cladding and tri-cladding waveguides, the slope efficiencies of the
      waveguide lasers were calculated to be 21.3% and 20%, and the maximum output
      powers measured were 82 mW and 84 mW, respectively. In addition, the annular
      modal profiles were obtained for these cladding waveguides.

PMID- 30117836
TI  - Enhanced plasmonic photovoltaic using embedded novel gear-shaped nanoparticles.
AB  - In this paper, novel gear-shaped nanoparticles are introduced for the first time
      to enhance the photovoltaic (PV) efficiency. This has been achieved via
      increasing the overall power absorption by the PV semiconductor material in both
      visible and near-infrared ranges. The modes of the new gear-shaped nanoparticles
      are investigated. A parametric study has been performed which demonstrates how
      the design parameters of the proposed nanoparticles can be engineered for best
      overall power absorption within a Si surrounding medium. A figure of merit (FoM)
      is defined that takes into account all objectives. An optimization technique is
      applied to obtain the optimum set of the gear's dimensions, penetration depth,
      and periodicity for the maximum possible FoM. The optimum gear-shaped
      nanoparticles design offers 48% enhancement in the FoM if compared with a bare Si
      block with no nanoparticles and 7% enhancement over the conventional disk-shaped
      nanoparticles. The enhancement gained by the embedded gear-shaped nanoparticles
      on the J-V characteristics of the PV is also studied, and the effects of changing
      the dimensions and the position of nanoparticles on the J-V characteristics
      enhancement are investigated.

PMID- 30117837
TI  - Efficient illumination angle self-calibration in Fourier ptychography.
AB  - Fourier ptychography captures intensity images with varying source patterns
      (illumination angles) in order to computationally reconstruct large space
      bandwidth-product images. Accurate knowledge of the illumination angles is
      necessary for good image quality; hence, calibration methods are crucial, despite
      often being impractical or slow. Here, we propose a fast, robust, and accurate
      self-calibration algorithm that uses only experimentally collected data and
      general knowledge of the illumination setup. First, our algorithm makes a fast
      direct estimate of the brightfield illumination angles based on image processing.
      Then, a more computationally intensive spectral correlation method is used inside
      the iterative solver to further refine the angle estimates of both brightfield
      and darkfield images. We demonstrate our method for correcting large and small
      misalignment artifacts in 2D and 3D Fourier ptychography with different source
      types: an LED array, a galvo-steered laser, and a high-NA quasi-dome LED
      illuminator.

PMID- 30117838
TI  - Quantitative estimation of elemental composition employing a synthetic generated
      spectrum.
AB  - Composition of multielement samples is estimated by using a synthetic generated
      spectrum utilizing a nonlinear fitting routine. By fitting simultaneously a large
      number of emission lines, the error in the estimation is minimized. The procedure
      for synthetic spectrum generation includes self-absorption of emission lines by
      taking into account the number density of different species in the plasma. The
      Stark width of different emission lines is iteratively calculated based on the
      observed width and the degree of self-absorption in the individual lines. This
      procedure is found to be successful for achieving convergence of the retrieval
      algorithm even for dense spectra as well as for resolving merged lines with
      accuracy. This scheme was applied on a stainless steel and brass sample, and the
      laser-induced breakdown spectroscopy results match well with the reference value
      obtained from the electron probe microanalyzer measurement.

PMID- 30117839
TI  - Classical and quantum analysis of propagation invariant vector flat-top beams.
AB  - Laser beams with a near uniform intensity profile, such as flat-top and super
      Gaussian beams, have found many applications, particularly in laser materials
      processing. Unfortunately such beams are not eigenmodes of free-space and, thus,
      alter their intensity profile during propagation. This may be overcome by
      creating vector flat-top beams. Here, we exploit the polarization dependent
      efficiency of spatial light modulators to create a vector flat-top beam that
      maintains its intensity profile and vector nature during propagation. We apply a
      holistic classical and quantum toolkit to analyze the dynamics of the vector
      state during propagation and demonstrate the versatility of these beams in an
      optical trapping and tweezing application. Our simple generation approach and
      holistic analysis toolbox will appeal to an audience who wish to employ these
      beams in a variety of applications.

PMID- 30117840
TI  - Broadening of the sum-frequency phase-matching bandwidth by temperature gradient
      in MgO:PPLN.
AB  - We demonstrate bandwidth broadening in cascaded MgO-doped periodically poled
      lithium niobate (MgO:PPLN) crystals (Lambda=10.3  MUm) using the temperature
      gradient technique. Up to 2.8 nm bandwidth at 600 nm spectral region is achieved
      using two 50 mm long cascaded MgO:PPLN crystals via sum frequency generation.
      This technique combines the merits of high conversion efficiency attributed to
      cascaded nonlinearity and the reconfigurability of temperature-gradient-induced
      chirp for broadening of the input wavelength acceptance range.

PMID- 30117841
TI  - Optimal iodine absorption line applied for spaceborne high spectral resolution
      lidar.
AB  - Spaceborne high spectral resolution lidar (HSRL) provides a wide range of
      observations, e.g., measurements of aerosol backscattering and extinction
      coefficients and aerosol depolarization ratio with high accuracy, which are of
      great significance to the study of air pollution monitoring and climate change.
      With different cells and finger temperatures, the transmittance of the different
      absorption lines of the iodine vapor filter at 532 nm wavelength was measured.
      The 1064 nm fundamental frequency pulse energy and the 532 nm frequency-doubled
      pulse energy output of different seeder laser wavelengths were measured. Based on
      the relationship among the laser output power, the absorption line shape of the
      iodine vapor filter, and the atmospheric model, the echo power was calculated and
      compared. The 1110 iodine absorption line was selected as the optimized filter
      for the HSRL, which could increase in 22% and 14% efficiency compared with the
      traditional 1109 line, and a new proposed 1105 line at the 532 nm HSRL channel at
      5 km altitude with an enhanced aerosol model, respectively.

PMID- 30117842
TI  - Superior signal persistence of circularly polarized light in polydisperse, real
      world fog environments.
AB  - We present simulation results quantitatively showing that circularly polarized
      light persists in transmission through several real-world and model fog
      environments better than linearly polarized light over broad wavelength ranges
      from the visible through the infrared. We present results for polydisperse
      particle distributions from realistic and measured fog environments, comparing
      the polarization persistence of linear and circular polarization. Using a
      polarization-tracking Monte Carlo program, we simulate polarized light
      propagation through four MODTRAN fog models (moderate and heavy radiation fog and
      moderate and heavy advection fog) and four real-world measured fog particle
      distributions (Garland measured radiation and advection fogs, Kunkel measured
      advection fog, and Sandia National Laboratories' Fog Facility's fog). Simulations
      were performed for each fog environment with wavelengths ranging from 0.4 to 12
      um for increasing optical thicknesses of 5, 10, and 15 (increasing fog density or
      sensing range). Circular polarization persists superiorly for all optical
      wavelength bands from the visible to the long-wave infrared in nearly all fog
      types for all optical thicknesses. Throughout our analysis, we show that if even
      a small percentage of a fog's particle size distribution is made up of large
      particles, those particles dominate the scattering process. In nearly all real
      world fog situations, these large particles and their dominant scattering
      characteristics are present. Larger particles are predominantly forward
      scattering and contribute to circular polarization's persistence superiority over
      broad wavelength ranges and optical thicknesses/range. Circularly polarized light
      can transmit over 30% more signal in its intended state compared to linearly
      polarized light through real-world fog environments. This work broadens the
      understanding of how circular polarization persists through natural fog particle
      distributions with natural variations in mode particle radius and single or
      bimodal characteristics.

PMID- 30117843
TI  - Optofluidic lenses with horizontal-to-vertical aspect ratios in the subunit
      regime.
AB  - Elliptical optofluidic lenses can provide tunable optical parameters in different
      optical planes. This tunability is achieved through modifications to the aspect
      ratio (AR). We present an optofluidic lens with a subunit AR. In our experimental
      analysis, we alter the shape of the microdroplet and observe a 10% reduction in
      the AR on applying a high voltage across the microdroplet. In our theoretical
      analysis, we observe improved tunability of focal length, longitudinal spherical
      aberration, and beam cone angle in the subunit AR regime compared to the
      superunit AR regime. We ultimately test and characterize the optofluidic lens in
      an imaging application.

PMID- 30117844
TI  - Eavesdropping of display devices by measurement of polarized reflected light.
AB  - Display devices, or displays, such as those utilized extensively in cell phones,
      computer monitors, televisions, instrument panels, and electronic signs, are
      polarized light sources. Most displays are designed for direct viewing by human
      eyes, but polarization imaging of reflected light from a display can also provide
      valuable information. These indirect (reflected/scattered) photons, which are
      often not in direct field-of-view and mixed with photons from the ambient light,
      can be extracted to infer information about the content on the display devices.
      In this work, we apply Stokes algebra and Mueller calculus with the edge overlap
      technique to the problem of extracting indirect photons reflected/scattered from
      displays. Our method applies to recovering information from linearly and
      elliptically polarized displays that are reflected by transmissive surfaces, such
      as glass, and semi-diffuse opaque surfaces, such as marble tiles and wood
      furniture. The technique can further be improved by applying Wiener filtering.

PMID- 30117845
TI  - Corrected calibration algorithm with a fixed constraint relationship and an error
      compensation technique for a binocular vision measurement system.
AB  - This paper is concerned with the precise calibration algorithm and error
      compensation technique for a binocular vision measurement system. By invoking a
      fixed constraint relationship between the binocular cameras, these two cameras
      can be preferably bound together as one camera, which means that in each
      iteration only one camera needs external parameter tuning for optimized
      encapsulation, and the iteration time is reduced. The global optimal solutions
      are obtained by substituting the initial iterative solutions into the optimized
      iterative equations of the spatial points. The derived improved iterative
      algorithm obtains the camera parameters with high precision and performs better
      in noise resistance. Moreover, the error compensation matrix is constructed to
      correct the relative pose of binocular cameras, upon which solutions to the error
      compensation matrix are solved via the unit quaternion. Consequently, the
      relative pose matrix is revised, allowing for further improvement in the
      calibration performance. Finally, simulation and practical experiments are
      demonstrated. The relevant results confirm the precision and robustness of the
      proposed approach.

PMID- 30117846
TI  - Average bit error rate performance analysis of a low-density parity-check-coded
      orthogonal frequency-division multiplexing FSO system under Malaga distribution
      considering atmospheric attenuation and pointing errors.
AB  - The average bit error rate (ABER) performance of low-density parity-check (LDPC)
      coded orthogonal frequency-division multiplexing (OFDM) free-space optical
      communication system with K-ary quadrature amplitude modulation (QAM) and phase
      shift keying (PSK) modulation schemes is investigated over the composite Malaga
      fading channel with atmospheric attenuation and pointing errors considered. The
      probability density function and cumulative distribution function regarding the
      aggregated channel model are derived with the help of the generalized Gauss
      Laguerre quadrature rule, the analytical ABER expressions for both QAM and PSK
      OFDM systems are then obtained. On the basis of them, the ABER performance is
      analyzed with different turbulence strengths, weather conditions, normalized beam
      width, normalized jitter, and specifically, different values of Malaga
      distribution parameter rho. Monte Carlo simulation is offered to confirm the
      correctness of the proposed ABER models. Moreover, LDPC codes are added into the
      simulation to enhance system performance. The result shows that, for the same
      turbulence, weather, and pointing error conditions, whether the LDPC codes are
      taken into account or not, the ABER performance of 16-QAM OFDM system is better
      than that of 16-PSK OFDM system over the Malaga fading channel, and the ABER
      result decreases with higher rho for both modulation schemes. Furthermore, the
      LDPC coding can significantly improve the system performance over this aggregated
      fading channel for these two modulation schemes, and a lower LDPC code rate can
      obtain a better ABER performance. This work is beneficial for free-space optical
      system design.

PMID- 30117847
TI  - Hybrid lens design for ultrawide-angle imaging with a high Strehl ratio in a
      folded system.
AB  - When UV-curable material is used with a spherical glass lens, it is classified as
      a hybrid lens and can provide a new degree of freedom in designing a lens system.
      This method is used to explore the optical limitation of an ultrawide-angle
      imaging system of a folded structure, which is utilized to achieve a compact
      volume. The f-number and field of view of the system are 2.0 and 190 degrees ,
      respectively. Diffraction-limited performance is achieved within a field of view
      of 80 degrees  with Strehl ratios greater than approximately 80%. Even at the
      maximum field of view of 190 degrees , the Strehl ratio is nearly 75%. The lens
      configuration is NNPNN, where N and P denote negative and positive optical power,
      respectively; this configuration uses only two aspherical hybrid lens surfaces.
      Comparisons of different optimizations are also provided.

PMID- 30117848
TI  - Surface ripple suppression in subaperture polishing with fragment-type tool
      paths.
AB  - In order to reduce the ripple-induced effect in subaperture polishing of high
      power laser optics, the tool paths are investigated and optimized in this study.
      Various fragment-type curves (i.e., fractal and fractal-like unicursal curves)
      are designed as tool paths, and most importantly, a novel algorithm for
      generating a random fractal-like tool path is proposed in detail. Compared with
      scanning paths, fragment-type paths possess multi-directionality during multiple
      polishing iterations, which could better smooth the surface texture and restrain
      the polishing-induced surface ripples. In particular, the random fractal-like
      path exhibits high randomness, boundary adaption, and step-length arbitrariness,
      which make it more flexible and powerful for iterative polishing. Experiments
      were conducted on a computer numerical control machine, with conclusions that
      during iterative polishing, (1) the repetitive usage of a single fractal path
      would aggravate surface ripples; (2) the combination of multiple fractal paths or
      using the random fractal-like path can restrain surface ripples efficiently; and
      (3) pitch pads exhibit a better ripple-smoothing effect than polyurethane. The
      proposed random fractal-like path is a good prospect for the manufacture of high
      power laser optics, which demands very low surface ripples.

PMID- 30117849
TI  - Ridge waveguide assisted highly efficient transverse-electric-pass polarizer
      based on a hybrid plasmonic waveguide.
AB  - An ultra-compact and low-loss transverse-electric (TE)-pass polarizer is proposed
      by utilizing a hybrid plasmonic ridge waveguide structure on a silicon-on
      insulator platform. Since the transmission of a plasmonic polarizer is greatly
      influenced by the interaction between the metal and the optical field, there is a
      large insertion loss (IL) in the polarizer based on a hybrid plasmonic waveguide.
      Here, the electric field distribution and the periodic coupling between the
      fundamental transverse magnetic mode and plasmonic mode are taken into
      consideration to decrease the IL and shorten the length of the device. For a 4.2
      MUm-long polarizer, numerical simulations with the finite-differential-time
      domain method show that it has a large extinction ratio (ER) of ~29.5  dB with a
      low IL of 0.18 dB at the central wavelength 1550 nm. In addition, a more than 23
      dB ER is achieved across a wide bandwidth of 100 nm.

PMID- 30117850
TI  - Modeling and calibration of a precise optical positioning system based on four
      linear cameras.
AB  - This study is intended for modeling and calibration of a precise optical
      positioning system for tracking 3D positions of remote targets in a large space.
      This system is made up of four linear cameras, which are equipped with
      cylindrical lenses. The four cameras are paired up as two identical groups. Each
      camera group is composed of two linear cameras that are packaged together with
      their imaging orientations normal to each other. The specially designed structure
      makes the system superior to existing three-linear-CCD-camera systems used for
      position tracking, in the efficiency of eliminating distortion of cylindrical
      lenses, a long-standing problem in precise calibration of linear cameras with
      cylindrical lenses. During the modeling and calibration process, each camera
      group is treated as an integrated 2D image sensor. A complete imaging model is
      established for each camera group, and the object-space error is used in
      calibration for obtaining optimal camera parameters. Simulative and real
      experiments have verified that, when the two cameras in each group have a good
      distortion consistency, the proposed calibration approach can effectively fit the
      model of linear cameras and correct the distortion of cylindrical lenses, thus
      leading to a significant improvement of positioning accuracy.

PMID- 30117851
TI  - Modeling mutually coupled non-identical semiconductor lasers on photonic
      integrated circuits.
AB  - We model the situation of two lasers in a face-to-face arrangement, optically
      coupled through an attenuating element, where the distance between the lasers is
      on a scale typical in photonic integration (hundreds of micrometers to
      millimeters). We account for the existence of a frequency difference between the
      two single-mode lasers. Modified versions of the Lang-Kobayashi equations were
      employed to describe the interaction. By solving this delay differential equation
      system, we characterized different dynamical regimes including one- and two-color
      states and self-pulsations. We focus on the effect varying coupling strength and
      detuning between the lasers has on the frequencies of the lasers. Using the
      results of this frequency study, we identify the bifurcations causing changes
      between the different frequency regimes.

PMID- 30117852
TI  - Development of a photopolymer holographic lens for collimation of light from a
      green light-emitting diode.
AB  - A holographic optical element (HOE) was developed to collimate a monochromatic
      light-emitting diode (LED). The fabrication was achieved by the interference of
      collimated and diverging beams from a 532 nm laser to produce the required
      photonic structure in a self-developing photopolymer material. The experimental
      values of diffraction efficiency and spatial period across the HOE were compared
      with their expected theoretical values. Good agreement was found for the spatial
      period; however, the diffraction efficiency varied significantly across the lens.
      In this paper, two approaches have been taken to address this variation: (1)
      modification of recording geometry and (2) optimization of recording intensity
      and exposure time at constant energy. The performance of an optimized HOE
      (cylindrical holographic lens) was then demonstrated using a 532 nm laser beam.
      The optimized conditions for the cylindrical holographic lens were used to
      fabricate a spherical holographic lens of the same numerical aperture for LED
      applications. This type of lens has the potential to be used in combination with
      LED sources.

PMID- 30117853
TI  - Fast quantitative fluorescence authentication of milk powder and vanillin by a
      line-scan hyperspectral system.
AB  - We present a fast hyperspectral line-scan fluorescence imaging system to verify
      the feasibility of quantitative fluorescence authentication of powders. Vanillin,
      which is restricted for use in milk powder, especially in milk powder for
      infants, is mixed with milk powder in different mass concentrations (5%, 10%,
      30%, 50%, 70%, and 90%). Mixed powders are located on a motorized linear stage. A
      405 nm line laser is utilized to excite the fluorescence of the sample. Based on
      galvo scanning, we can generate a laser line with high spatial resolution and
      high-intensity density on the samples. An imaging spectrometer with a
      complementary metal-oxide semiconductor (CMOS) camera as detector is built. The
      spectral range of the spectrometer is 365-810 nm, with about 1 nm spectral
      resolution. One snapshot of the CMOS can acquire the fluorescent spatial and
      spectral information of a line region in 100 ms. By scanning the motorized linear
      stage, we obtain the fluorescence hypercube of the sample. A 100*1926*1216
      hypercube, which covers an area of 15  mm*5  mm, is obtained in 50 s. The imaging
      speed can be enhanced further by increasing the intensity of the excitation laser
      and the sensitivity of the area camera. Fully constrained least squares, a linear
      spectral mixture analysis, is utilized to analyze the hypercube obtained by our
      homemade imaging spectrometer, thus obtaining the pixel concentration of vanillin
      in each mixed powder. Linear regression analysis is used for the pixel
      concentration and mass concentration of vanillin. A linear relationship with
      coefficient of determination R2 equal to one is observed, which demonstrates the
      capability of fluorescence hyperspectral quantitative analysis in powders.

PMID- 30117854
TI  - Jones matrix physical parameters for media in inhomogeneous fields.
AB  - Inhomogeneous media are affected by a physical or an electromagnetic field, where
      the off-diagonal elements of the Jones matrix are complex numbers with both real
      and imaginary parts. Inhomogeneities of the electromagnetic field result in the
      eigenvalue coordinate system changing along the light path. In this study, we
      used the unitary transformation to propose a Jones matrix of the inhomogeneous
      field-induced medium with three physical or electromagnetic parameters: the
      medium's phase delay, induction angle, and inhomogeneous angle. This Jones matrix
      and the integral formulas of its three parameters are applicable to not only
      remarkable optical effects but also for the light propagation process of
      inhomogeneous-field-induced media.

PMID- 30117855
TI  - Double-wedge prism scanner for application in thermal imaging systems.
AB  - In this paper, double-wedge prisms, also known as Risley prisms, and composed of
      two wedge prisms, are presented with assemblies in four configurations. In the
      double-wedge prism scanner, the center of the two wedge prisms is aligned with
      the optical axis; thus, the optical system and mechanical structure are simple.
      In contrast to conventional scanners, its assembly is compact, robust, and
      insensitive to vibrations and wobbles. However, the relationship between the
      deviated and rotated angles is not linear, and the trajectory of the scan pattern
      is nonrectilinear; therefore, double-wedge prisms have rarely been used in
      imaging systems as a one-dimensional scanner until now. This study presents the
      optical characteristics of double-wedge prisms and proposes methods to solve the
      problems mentioned above. The experimental results demonstrate that the double
      wedge prisms can be used in an imaging system as a one-dimensional scanner.

PMID- 30117856
TI  - Semicylindrical microresonator: excitation, modal structure, and Q-factor.
AB  - A semicylindrical microresonator with relatively simple excitation by a plane
      wave is studied. The resonator is formed on the base of a
      dielectric/metal/dielectric structure, where the wave energy penetrates into the
      resonator through a thin metal layer and is stored in a semicylindrical
      dielectric with high permittivity. The proposed microresonator combines features
      of Fabry-Perot and whispering-gallery-mode resonators. Dependence of radiation
      losses on the radius and materials are estimated by theoretical analysis, while
      excitation by a plane wave is shown via numerical analysis. A quality Q-factor of
      the resonator up to 104 can be achieved at a radius of the semicylinder of
      several micrometers.

PMID- 30117857
TI  - Time-delay-signature-suppressed broadband chaos generated by scattering feedback
      and optical injection.
AB  - We propose and demonstrate a novel scheme to generate time-delay-signature
      suppressed broadband chaotic light by using an optically injected laser diode
      subjected to scattering light feedback. The achievement of broadband chaos is
      based on the interaction between the injection light and chaotic light from the
      scattering feedback semiconductor laser via beating. A single-mode fiber as a
      continuous scatterer is specially used as a feedback cavity to introduce random
      feedback, which could truly eliminate the time delay signature of chaotic light.
      The chaotic light with a power spectrum that extends to 13.6 GHz within 3 dB is
      experimentally achieved.

PMID- 30117858
TI  - Self-processing photopolymer materials for versatile design and fabrication of
      holographic sensors and interactive holograms.
AB  - The aim of this paper is to discuss the benefits as well as the limitations of
      utilizing photopolymer materials in the design of holograms that are responsive
      to changes in their environment, such as changes in the concentration of a
      specific substance, temperature, and pressure. Three different case studies are
      presented, including both surface and volume phase holograms, in order to
      demonstrate the flexibility in the approach of utilizing holographic
      photopolymers for the design of sensors and interactive optical devices. First, a
      functionalized surface relief hologram is demonstrated to operate as an optical
      sensor for the detection of metal ions in water. The sensitivity and selectivity
      of the sensor are investigated. The second example demonstrates a volume
      transmission hologram recorded in a temperature-sensitive photopolymer and the
      memory effects of its exposure to elevated temperature. Finally, a pressure
      sensitive reflection hologram that changes color under application of pressure is
      characterized, and its potential application in document authentication is
      described.

PMID- 30117859
TI  - Investigation of multiple laser shock peening on the mechanical property and
      corrosion resistance of shipbuilding 5083Al alloy under a simulated seawater
      environment.
AB  - To investigate the effect of laser shock peening (LSP) with different LSP impacts
      on the mechanical properties in artificial seawater and corrosion resistance of
      shipbuilding 5083Al alloy in 3.5% NaCl solution, wear property and
      electrochemical corrosion resistance tests were performed by a ball-on-disk
      sliding wear tester and electrochemical workstation. The wear mass losses of the
      samples treated by 1 and 3 LSP impacts are much lower, by 55.22% and 65.94%,
      respectively, than those of untreated specimens in artificial seawater. Compared
      with the untreated sample, the electrochemical corrosion rate of the treated
      samples decreased by 74.91% and 95.03% after being treated by 1 and 3 LSP
      impacts, respectively. The reasons for the enhancement of the wear properties and
      electrochemical corrosion behavior were caused by the increased residual stress
      and microhardness after the LSP treatment.

PMID- 30117860
TI  - High-sensitive absorption measurement in transparent isotropic dielectrics with
      time-resolved photothermal common-path interferometry.
AB  - We propose a time-resolved photothermal common-path interferometry scheme at fast
      heating in the absence of heat diffusion and employ it to measure absorption in
      Suprasil 311 silica glass (2.8.10-6  cm-1) at a wavelength of 1071 nm and
      continual absorption in laboratory air (2.9.10-8  cm-1) for a signal-to-noise
      ratio of 100/1. The absorption was measured at a thermally induced phase
      incursion of less than 0.1 rad in a heating beam, which guaranteed correct
      calibration. To calibrate this scheme, we developed a theory of diffraction on
      deformations taking into account the stresses arising in an inhomogeneous
      temperature field. This allowed us to use a standard glass K8 for calibration.
      The low level of noise and time resolution of pulsed signals allowed the
      distinguishing of the contributions of Kerr and striction nonlinearities to
      absorption measurements in Suprasil 311 silica glass and enabled the observance
      of the time evolution of strictional deformations. Additionally, an anomalous
      temporal development of the absorption of broadband laser radiation in
      atmospheric air at 2.9.10-8  cm-1 has been revealed.

PMID- 30117861
TI  - Multiple-view polarimetric camera.
AB  - A multiple-view polarimetric camera is developed. The system uses four separate
      action cameras, and software is employed to map the images onto each other in
      order to generate the Stokes vectors, the degree of linear polarization, and the
      angle images. To ensure robustness, an automated calibration system has been
      developed that ensures the pixels are correctly mapped. Video frame
      synchronization is also developed.

PMID- 30117862
TI  - Top-of-atmosphere reflectance over homogeneous Lambertian and non-Lambertian
      surfaces.
AB  - In this study, the effects of the Lambertian assumption on the top-of-atmosphere
      reflectance are evaluated through comparison with calculations derived using a
      more detailed bidirectional reflectance distribution function under different
      atmospheric, lighting, and viewing conditions. The numerical experiments are
      performed for background, dusty, and cloudy models of the atmosphere in spectral
      channels of 0.44 and 0.87 MUm. In the case of a background or dusty medium over
      the terrestrial surface, the overestimation of the top-of-atmosphere reflectance
      in the forward-scatter viewing direction and underestimation in the backscatter
      one are observed. The angular range as well as magnitude of the discrepancy is
      noticeably narrower and lower, respectively, when the atmosphere is more turbid
      and the wavelength is shorter. The use of the Lambertian assumption instead of
      "true" ocean reflectance leads to a significant underestimation of the top-of
      atmosphere reflectance in the forward-scatter direction and a moderate
      overestimation of reflectance in the backscatter one. The ocean reflectance
      generally exhibits a high dependence on wind, which affects the reflected solar
      radiation distribution around the forward-scatter direction. Analysis of
      simulation results for an overcast sky showed that, in general, the multiple
      scattered radiation smoothes the anisotropy effects. However, there are
      conditions at which the choice of a bidirectional reflectance distribution
      function model is significant: in the case of thin cirrus cloudiness over the
      ocean at large solar zenith angles and stratus cloudiness with an optical
      thickness of at least 5 over a vegetation cover or ocean in the near-infrared
      region of the spectrum.

PMID- 30117863
TI  - Investigation of thermoforming mechanism and optical properties' change of
      chalcogenide glass in precision glass molding.
AB  - Chalcogenide glasses are emerging as enabling materials for low-cost infrared
      optics due to their transparency in shortwave-to-longwave infrared bands and the
      possibility to be mass produced by precision glass molding (PGM), a near net
      shape process. This paper aims to evaluate the thermoforming mechanism of As40S60
      glass around its glass transition temperature (Tg) and investigate its refractive
      index change and residual stresses in a molded lens during and after PGM. First,
      a constitutive model was introduced to precisely predict the material behavior in
      PGM by integrating subroutines into a commercial finite element analysis (FEA)
      software. This modeling approach utilizes the Williams-Landel-Ferry equation and
      Tool-Narayanaswamy-Moynihan model to describe stress relaxation and structural
      relaxation behaviors, respectively. The numerical simulation revealed that the
      cooling rate above glass transition temperature (Tg) can introduce large geometry
      deviations to the molded optical lens. The residual stresses in a molded lens are
      generated mainly at the temperature around Tg due to the heterogeneity of thermal
      expansion from viscoelastic to solid state, while structural relaxation occurs
      during the entire cooling process. The refractive index variations inside molded
      lenses were predicted by performing finite element method simulation and further
      evaluated by measuring wavefront changes using an infrared Shack-Hartmann
      wavefront sensor, while the residual stresses trapped inside the molded lenses
      were obtained by using a birefringence method. A combination of measurements of
      the molded infrared lenses and numerical simulation results provided an
      opportunity for optical manufacturers to better understand the mechanism and
      optical performance of chalcogenide glasses during and after PGM.

PMID- 30117864
TI  - Optofluidic adaptive optics.
AB  - We introduce a transmissive refractive adaptive optics system featuring a
      deformable transparent optofluidic wavefront modulator and a sensorless wavefront
      error estimation algorithm. The wavefront modulator consists of a cavity filled
      with an optical liquid which is sealed by a deformable elastic polymer membrane.
      Deformation of the membrane is achieved through electrostatic actuation using 25
      transparent indium tin oxide electrodes buried in the cavity. Modulation of the
      two-dimensional phase distribution generated by the system is performed using
      open loop control both with and without active wavefront sensing. For the latter,
      a progressive modal decomposition algorithm is used to estimate and correct
      distortion in the point-spread function (PSF) of the wavefront arising due to the
      optical system and other sources of wavefront distortion. Using this control
      method, we experimentally demonstrate high-fidelity recreation of Zernike modes
      up to the fourth order, and blind (sensorless) PSF correction in a wide-field
      microscope.

PMID- 30117865
TI  - Plasmonic filter and sensor based on a subwavelength end-coupled hexagonal
      resonator.
AB  - In this paper, an end-coupled hexagonal resonator inserted with dual parallel
      metallic blocks is proposed based on subwavelength metal-insulator-metal
      waveguides. When the blocks are vertically inserted into the resonator, more
      transmission channels (three peaks) with symmetrical spectral shapes than that
      (one peak) of the perfect hexagonal resonator are achieved in the same wavelength
      range. The transmission peaks all have high transmittances; thus, the structure
      can be performed as an on-chip optical filter. When the blocks are horizontally
      distributed in the resonator, the antinode and node of the magnetic field for the
      expected mode will arise inside and outside the blocks, leading to the mode
      interactions. Subsequently, Fano resonance with an asymmetrical peak is achieved
      in the structure. High index sensitivity and high figure of merit, which are
      significant factors for optical sensors, are investigated by using the finite
      difference time-domain method. The proposed structure can highly support the
      development of integrated photonics and find wide applications in the on-chip
      optical filtering and sensing areas.

PMID- 30117866
TI  - Nonlinear mapping method for the generation of an elemental image array in a
      photorealistic pseudoscopic free 3D display.
AB  - Limited available elemental image array resources may be the most severe
      bottleneck for the promotion and application of integral-imaging-based 3D
      display. We propose a nonlinear mapping method for the generation of an elemental
      image array to get a photorealistic pseudoscopic free 3D display based on the
      parallel light field reconstruction nature of the integral imaging system. All
      the light rays emitted from the display panel are classified into a corresponding
      parallel light field according to its direction, and all the parallel light
      fields are captured as orthogonal projections of the scene before synthesizing
      all the orthogonal projections using a nonlinear mapping method to form the final
      elemental image array. Preliminary optical experiments as well as ray optical
      analysis are conducted to prove the feasibility and validity of the proposed
      method. The proposed method can exploit most of the current 3D platform. It is an
      effective and efficient way to generate an elemental image array.

PMID- 30117867
TI  - Simultaneous achievement of highly birefringent and nonlinear photonic crystal
      fibers with an elliptical tellurite core.
AB  - A novel photonic crystal fiber (PCF) with an elliptical tellurite core is
      proposed to realize high birefringence and high nonlinearity simultaneously as
      well as low confinement loss at the wavelength of 1.55 MUm. The guiding
      properties, such as the birefringence, the nonlinearity, and the confinement
      loss, have been investigated by using the full vectorial finite element method.
      The results show that the birefringence and the nonlinear coefficient can be up
      to 7.57*10-2 and 188.39  W-1 Km-1, respectively, and the confinement loss can be
      only 10-9  dB/m. The proposed PCF can find potential applications in optical
      fiber sensing, polarization-maintaining transmission, and super-continuum
      generation.

PMID- 30117868
TI  - Bendable large-mode-area fiber with a non-circular core.
AB  - We investigate mode-area-scaling and bending performances of a Yb-doped large
      mode-area fiber with an elongated non-circular core. Such fiber can be bent in
      the plane of its short axis to suppress bending effects, such as mode area
      reduction and mode profile distortion. Meanwhile, the other orthogonal axis can
      be stretched for mode area scaling. Calculations show that for fibers with the
      same mode area, the higher the aspect ratio between the long axis and short axis,
      the less sensitive the fiber will be to bending effects. However, mode area
      scaling is limited by the increased beat length (BL) between the fundamental mode
      (FM) and the second-order mode, leading to mode degeneracy at higher aspect
      ratios. Within the 100 mm BL, the FM area is scalable to 3000  MUm2 in a bent
      fiber. To facilitate FM operation, we study mode-selective gain through confined
      doping. Thanks to the small bending distortions, the confined-doping approach
      works well in the bent large-mode-area fiber. In addition, the advantage of
      tandem pumping is also discussed in terms of preferential modal gain. A non
      circular core fiber with a 41 MUm short axis and 120 MUm long axis was fabricated
      in-house. We evaluated the fiber in a linear laser cavity pumped by a 975 nm
      laser diode. The maximum output power obtained was 191 W, with slope efficiency
      of approximately 67% with respect to launched pump power. The output signal has
      good beam qualities with M2 of ~1.5 and ~3.1, respectively, along the short and
      long axis.

PMID- 30117869
TI  - Improving the throughput of automated holographic optical tweezers.
AB  - The purpose of this work is to introduce three improvements to automated
      holographic-optical-tweezers systems that increase the number and speed of
      particles that can be manipulated simultaneously. First, we address path planning
      by solving a bottleneck assignment problem, which can reduce total move time by
      up to 30% when compared with traditional assignment problem solutions. Next, we
      demonstrate a new strategy to identify and remove undesired (e.g., misshapen or
      agglomerated) particles. Finally, we employ a controller that combines both
      closed- and open-loop automation steps, which can increase the overall loop rate
      and average particle speeds while also utilizing necessary process monitoring
      checks to ensure that particles reach their destinations. Using these
      improvements, we show fast reconfiguration of 100 microspheres simultaneously
      with a closed-loop control rate of 6, and 10 Hz by employing both closed- and
      open-loop steps. We also demonstrate the closed-loop assembly of a large pattern
      in a continuously flowing microchannel-based particle-delivery system. The
      proposed approach provides a promising path toward automatic and scalable
      assembly of microgranular structures.

PMID- 30117870
TI  - Surface-enhanced Raman scattering for rapid hematopoietic stem cell
      differentiation analysis.
AB  - Raman-spectroscopy-based methods, such as surface-enhanced Raman spectroscopy,
      are a well-evolved method to molecular fingerprint cell types. Here we
      demonstrate that surface-enhanced Raman spectroscopy can enable us to distinguish
      cell development stages of bone marrow hematopoietic stem cells towards red blood
      cells through the identification of specific surface-enhanced Raman spectroscopy
      biomarkers. The approach taken here is to allow cells to take in gold
      nanoparticles as Raman enhancement platforms for kinetic structural observations
      presented here through the view of the multidimensional parameter contribution,
      thereby enabling profiling of bone marrow hematopoietic stem cells acquired from
      proliferation (stage one), differentiation (stage two), and mature red blood
      cells (stage three).

PMID- 30117871
TI  - Chiral sculptured thin films for circular polarization of mid-wavelength infrared
      light.
AB  - Being an assembly of identical upright helices, a chiral sculptured thin film
      (CSTF) exhibits the circular Bragg phenomenon and can therefore be used as a
      circular polarization filter in a spectral regime called the circular Bragg
      regime. This has been already demonstrated in the near-infrared and short
      wavelength infrared regimes. If two CSTFs are fabricated in identical conditions
      to differ only in the helical pitch, and if both are made of a material whose
      bulk refractive index is constant in a wide enough spectral regime, then the
      center wavelengths of the circular Bragg regimes of the two CSTFs must be in the
      same ratio as their helical pitches by virtue of the scale invariance of the
      frequency-domain Maxwell postulates. This theoretical result was confirmed by
      measuring the linear transmittance spectra of two zinc-selenide CSTFs with
      helical pitches in the ratio 1:7.97. The center wavelengths were found to be in
      the ratio 1:7.1, and the deviation from the ratio of helical pitches is
      explainable at least in part because the bulk refractive index of zinc selenide
      decreases a little with wavelength. We concluded that CSTFs can be fabricated to
      function as circular polarization filters in the mid-wavelength infrared regime.

PMID- 30117872
TI  - Broadband time-resolved multi-channel functional near-infrared spectroscopy
      system to monitor in vivo physiological changes of human brain activity.
AB  - We have developed a broadband time-resolved multi-channel near-infrared
      spectroscopy system that can monitor the physiological responses of the adult
      human brain. This system is composed of a supercontinuum laser for the source
      part and of an intensified charge-coupled device camera coupled with an imaging
      spectrometer for the detection part. It allows the detection of the spectral,
      from 600 to 900 nm, and spatial dimensions as well as the arrival time of photon
      information simultaneously. We describe the setup and its characterization in
      terms of temporal instrument response function, wavelength sensitivity, and
      stability. The ability of the system to detect the hemodynamic response is then
      demonstrated. First, an in vivo experiment on an adult volunteer was performed to
      monitor the response in the arm during a cuff occlusion. Second, the response in
      the brain during a cognitive task was monitored on a group of five healthy
      volunteers. Moreover, looking at the response at different time windows, we could
      monitor the hemodynamic response in depth, enhancing the detection of the
      cortical activation. Those first results demonstrate the ability of our system to
      discriminate between the responses of superficial and deep tissues, addressing an
      important issue in functional near-infrared spectroscopy.

PMID- 30117873
TI  - Behavior of tiled-aperture arrays fed by vector partially coherent sources.
AB  - This paper explores the far-zone behavior of partially coherent arrays. We derive
      an expression for the far-zone spectral density valid for any array composed of
      circular elements and fed by fields with Schell-model cross-spectral density
      functions. This expression is written as the sum of convolution integrals, making
      it easy to physically interpret. We discuss this expression at length and present
      examples. Lastly, we validate our analysis by comparing Monte Carlo averages from
      wave-optics simulations with theory. We conclude this paper with a brief summary
      of the results and potential uses of our work.

PMID- 30117874
TI  - Detection and identification of transformer winding strain based on distributed
      optical fiber sensing.
AB  - At present, transformer winding strain monitoring is divided mainly into off-line
      detection and on-line detection. Due to the interference of the complex
      electromagnetic environment, on-line detection has not been widely used. Although
      off-line detection is more mature, it can not accurately judge the winding strain
      form. Based on the above problems, this research investigated a strain gauge
      strain detection method based on distributed fiber optic sensing, and proposes a
      winding strain identification method based on the S-transform and an extreme
      learning machine (ELM). First, the deformation of the winding in the process of
      transformer operation is simulated, and the corresponding Brillouin frequency
      shift is collected. Then, the time-frequency analysis of the strain signal is
      carried out using an S-transform, and the transformed time-frequency feature is
      extracted as the input sample to the neural network. An ELM was used for training
      identification. Experimental results show that the method can effectively
      identify the common winding deformation form, and that the recognition effect is
      better and the accuracy is high.

PMID- 30117875
TI  - Dependence of the imaging properties of the liquid lens with variable focal
      length on membrane thickness.
AB  - This paper presents the influence of membrane thickness on imaging properties of
      membrane liquid lenses with variable focal length. Approximate formulas for
      varying thickness of spherically and parabolically deformed membrane were
      derived, which allows us to determine their influence on quality of imaging
      properties of a membrane liquid lens. Furthermore, formulas for wave spherical
      aberration calculation of a membrane and liquid lens body were derived. It has
      been shown that the influence of membrane thickness and its changes on wave
      spherical aberration is negligible from a practical point of view.

PMID- 30117876
TI  - Electric-arc-induced strength-controllable weak polarization mode coupling in
      polarization maintaining fiber.
AB  - An electric-arc-based scheme to generate strength-controllable weak polarization
      mode coupling (PMC) points in polarization maintaining fiber (PMF) is described.
      The resulting PMC strengths can be readily controlled to be in the very weak
      range of -60 to -40  dB. In this range, excellent mechanical strength combined
      with high return loss is achieved. An experimental quasi-distributed temperature
      sensor is formed by three separate PMC points in a single PMF using the electric
      arc method.

PMID- 30117877
TI  - Determination of potassium in ceramic raw materials using laser-induced breakdown
      spectroscopy combined with profile fitting.
AB  - The determination of potassium (K) content in ceramic raw materials provides
      important references for ceramic sintering. To realize rapid, in situ, and real
      time analysis detection, a laser-induced breakdown spectroscopy (LIBS) system was
      set up to analyze K content in ceramic raw materials. However, the self
      absorption was the serious influence on the accuracy of K element analysis. In
      this work, a method of profile fitting with Lorentz function was proposed to
      reduce the self-absorption effect in LIBS. After Lorentz fitting, the
      determination coefficient (R2 factor) for K element improved from 0.993 to 0.998,
      the root mean square error of cross-validation reduced from 0.458 wt. % to 0.145
      wt. %, and the average relative error reduced from 13.769% to 5.121%. The results
      indicate that the Lorentz fitting can effectively reduce the self-absorption
      effect, and improve the accuracy of quantitative analysis for K element.
      According to the results, the proposed approach can be a promising method for
      determination of elements that suffer from self-absorption in LIBS.

PMID- 30117878
TI  - Fiber-coupled vapor cell for a portable Rydberg atom-based radio frequency
      electric field sensor.
AB  - We demonstrate a movable, Rydberg atom-based radio frequency (RF) electric (E)
      field probe. The technique is based on electromagnetically induced transparency
      and Autler-Townes splitting. Two fibers attached to a 10 mm cubic Cs133 vapor
      cell are used to couple counter-propagating probe and control lasers through the
      cell. This all-dielectric fiber-coupled sensor can be moved from the optics table
      to locations more suitable for RF (gigahertz to sub-terahertz) E-field
      measurements and calibrations.

PMID- 30117879
TI  - Nonlocal low-rank-based blind deconvolution of Raman spectroscopy for automatic
      target recognition.
AB  - Raman spectroscopy often suffers from the problems of band overlap and random
      noise. In this work, we develop a nonlocal low-rank regularization (NLR) approach
      toward exploiting structured sparsity and explore its applications in Raman
      spectral deconvolution. Motivated by the observation that the rank of a ground
      truth spectrum matrix is lower than that of the observed spectrum, a Raman
      spectral deconvolution model is formulated in our method to regularize the rank
      of the observed spectrum by total variation regularization. Then, an effective
      optimization algorithm is described to solve this model, which alternates between
      the instrument broadening function and latent spectrum until convergence. In
      addition to conceptual simplicity, the proposed method has achieved highly
      competent objective performance compared to several state-of-the-art methods in
      Raman spectrum deconvolution tasks. The restored Raman spectra are more suitable
      for extracting spectral features and recognizing the unknown materials or
      targets.

PMID- 30117880
TI  - Silicon-wire optical demultiplexers based on multistage delayed Mach-Zehnder
      interferometers for higher production yield.
AB  - We report better spectral uniformity in Si-wire-based multistage delayed Mach
      Zehnder interferometer (DMZI) type optical multiplexers/demultiplexers
      (MUX/DeMUX). Based on a 300 mm silicon-on-insulator wafer-scale ArF-immersion
      lithography process that guarantees higher phase controllability for low
      insertion loss, spectral flatness, and low crosstalk, we were able to further
      improve spectral uniformity across the wafer by optimizing the waveguide width
      within the optical path of each DMZI region. Irrespective of channel spacing in
      the wavelength domain, it was experimentally demonstrated that the filter
      spectral center wavelength deviation of the proposed DeMUXs was three times
      smaller than that of conventional ones. The proposed device scheme would also be
      attractive for arbitrary channel spacing and channel count, which makes the
      proposed scheme more practical in high-performance wavelength division
      multiplexing optical transceivers.

PMID- 30117881
TI  - Vibration phases estimation based on multi-channel interferometry for ISAL.
AB  - Target vibration introduces unexpected vibration phases in the echo signal of
      inverse synthetic aperture LADAR (ISAL). The vibration phases cause the imaging
      results to be defocused. How to estimate the vibration phases has always been one
      of the difficulties in ISAL imaging, and there has not been an effective
      solution. In this paper, two methods are proposed to estimate the vibration
      phases in different situations. The method based on multi-channel along-track
      interferometry (MCATI method) is for some cases that the target velocity vector
      is parallel to some baselines of ISAL. The method based on orthogonal
      interferometry (OI method) is for other cases that the target velocity vector is
      not parallel to any baseline of ISAL. In addition, a high signal to noise ratio
      (SNR) is essential for the MCATI and OI methods to get high estimation accuracy.
      Therefore, a large power-aperture product should be carefully considered in the
      ISAL system design. Furthermore, on the condition of low SNR, range cell
      accumulation is also helpful to reduce the influence of noise. Take the ISAL,
      which is utilized to image the satellite in 500 km orbit, as an example, the
      estimation accuracy can satisfy the demand of synthetic aperture imaging with 0
      dB single-pulse SNR and 300 range cell accumulation. The proposed methods are
      verified with simulation and experiment.

PMID- 30117882
TI  - Pulse propagation in hollow-core fiber at high-pressure regime: application to
      compression of tens of MUJ pulses and determination of nonlinear refractive index
      of xenon at 1.03  MUm: publisher's note.
AB  - This publisher's note corrects an author surname in the abstract and a reference
      in Appl. Opt.57, 4659 (2018)APOPAI0003-693510.1364/AO.57.004659.

PMID- 30117883
TI  - Noiseless optical encryption based on a complex secret key and a joint Fresnel
      transform correlator with a Billet split lens.
AB  - A noiseless optical cryptosystem based on a joint Fresnel transform correlator
      (JFTC) with a Billet split lens (BSL) was designed. Benefitting from the
      adjustable structure of the BSL, we can control the size and recording position
      of the joint Fresnel transform power distribution by changing the split width of
      the BSL. To avoid the text being affected by noise, we converted the text into
      quick response (QR) code in advance, then used the QR code as the plaintext and
      utilized the noise tolerance ability of the QR code to realize noiseless recovery
      of the text. In this cryptosystem, we designed a complex secret key (CSK) to
      replace the secret key made from a random phase mask, and the CSK consists of a
      QR code filter and a spiral phase mask. Because the QR code and spiral phase can
      be determined by a few simple data, the transmission and preservation of the CSK
      is convenient. Finally, the validity and feasibility of the cryptosystem were
      demonstrated, and the sensitivity of the CSK was researched by simulation and
      experiment.

PMID- 30117884
TI  - Space-variant video compression and processing in digital holographic microscopy
      sensor networks with application to potable water monitoring.
AB  - Water-related diseases affect societies in all parts of the world. Online sensors
      are considered a solution to the problems associated with laboratory testing in
      potable water. One of the most active research areas of such online sensors has
      been within optics. Digital holographic microscopy (DHM) has the potential to
      rival state-of-the-art techniques such as advanced turbidity measurement.
      However, its use as an online sensor is limited by the large data requirements
      typical for digital holographic video. In this paper, we provide a solution that
      permits DHM to be applied to a whole class of online remote sensor networks, of
      which potable water analysis is one example. The designed sensors incorporate a
      novel space-variant quantization algorithm to preprocess each frame of a video
      sequence before transmission over a network. The system satisfies the generally
      accepted requirements of an online system: automated, near real-time, and
      operating in a real environment. To verify the effectiveness of the design, we
      implemented and evaluated it in an active potable water facility.

PMID- 30117885
TI  - Hartmann-Shack wavefront sensing without a lenslet array using a digital
      micromirror device.
AB  - The common Hartmann-Shack wavefront sensor makes use of a lenslet array to sample
      in-parallel optical wavefronts. Here, we introduce a Hartmann-Shack wavefront
      sensor that employs a digital micromirror device in combination with a single
      lens for serial sampling by scanning. Sensing is analyzed numerically and
      validated experimentally using a deformable mirror operated in closed-loop
      adaptive optics with a conventional Hartmann-Shack wavefront sensor, as well as
      with a set of ophthalmic trial lenses, to generate controllable amounts of
      monochromatic aberrations. The new sensor is free of crosstalk and can
      potentially operate at kilohertz speed. It offers a reconfigurable aperture that
      can exclude unwanted parts of the wavefront.

PMID- 30117886
TI  - Ultracompact reference ultralow expansion glass cavity.
AB  - We present the first experimental characterization of our ultracompact,
      ultrastable laser. The heart of the apparatus is an original Fabry-Perot cavity
      with 25 mm length and pyramidal geometry, equipped with highly reflective
      crystalline coatings. The cavity, along with its vacuum chamber and optical
      setup, fits inside a 30 L volume. We have measured the cavity's thermal and
      vibration sensitivities and present our first estimation of the cavity fractional
      frequency instability at sigmay(1  s)=7.5*10-15.

PMID- 30117887
TI  - Tunable and passively Q-switched laser operation of Nd,Lu:CaF2 disordered
      crystal.
AB  - We report the first demonstration, to the best of our knowledge, of tunable and Q
      switched lasers based on diode-pumped Nd,Lu:CaF2 disordered crystal. A continuous
      tuning range of approximately 32 nm (1047-1079 nm) was obtained for tunable
      operations. A passively Q-switched laser was successfully achieved using a
      Cr4+:YAG as a saturable absorber. The shortest pulse width of 275 ns was obtained
      with a repetition rate of 1.85 kHz and corresponding peak power and single pulse
      energy of 189 W and 51.9 MUJ, respectively.

PMID- 30117888
TI  - Q-switched ytterbium-doped fiber laser via a thulium-doped fiber saturable
      absorber.
AB  - We demonstrated a reliable and stable Q-switched ytterbium-doped fiber laser
      centered at 1069 nm by employing a segment of 11 cm thulium-doped fiber (TDF) as
      a saturable absorber (SA) in the ring cavity. The fiber SA has an optical
      absorption of 1.35 dB at the Q-switched operating regime. As we increased the
      pump power from 109 mW to the maximum available pump power of 206 mW, a
      consistent Q-switched laser with output power ranging from 1.8 to 4.8 mW was
      attained. The pulse width narrowed from 4.9 to 2.87 MUs, whereas the repetition
      rate increased from 40 to 60.2 kHz. In addition, maximum pulse energy of 80.7 nJ
      and a maximum peak power of 28.1 mW were obtained at the maximum pump power. The
      signal to noise ratio (SNR) was around 47 dB. Our experimental study shows that a
      segment of TDF can be used as a Q-switcher in the 1 MUm fiber laser cavity to
      facilitate a reliable and robust microsecond pulse generation.

PMID- 30117889
TI  - Simultaneous determination of aerosol optical depth and exponent of the Junge
      power law from MODIS shortwave infrared bands over Qinghai Lake.
AB  - The water-leaving radiances for shortwave infrared (SWIR) channels can be
      negligible, and these channels also contain information on aerosol particle size.
      Therefore, the satellite-based data of SWIR channels can be used to estimate
      aerosol particle size over inland waters [Appl. Opt.39, 887 (2000)APOPAI0003
      693510.1364/AO.39.000887]. Supposing the actual atmospheric aerosol size
      distribution is based on the Junge power law, in this paper an iterative
      algorithm is used to simultaneously determine the aerosol optical depth (AOD) and
      the exponent of the Junge power law from Aqua MODIS L1B reflectance data of
      channels 1.64 MUm and 2.13 MUm over Qinghai Lake. Whether using the constant or
      variable aerosol complex refractive index (ACRI), the retrieved exponent of the
      Junge power law is always larger than the product value. Supposing the product
      values are accurate, for the constant ACRI, there are 68.91% and 25.48% pixels of
      acceptable retrieval AOD and the exponent of the Junge power-law value,
      respectively. Likewise, there are 71.63% and 43.75% pixels for variable ACRI.
      Compared with the retrieval error under constant ACRI, there are 58.65% and
      98.72% pixels, with a smaller AOD and Junge power-law index retrieval error under
      variable ACRIs, respectively. In addition, the precision of the AOD retrieved
      with variable ACRI is improved when the AOD product is less than 0.17. However,
      under the current environment with frequent aerosol particle pollution, the same
      ACRI for the ten wavelengths can achieve results with equivalent accuracy
      compared with variable ACRI.

PMID- 30117890
TI  - Influence of sample surface height for evaluation of peak extraction algorithms
      in confocal microscopy.
AB  - The axial resolution of confocal microscopy is not only dependent on optical
      characteristics but also on the utilized peak extraction algorithms. In previous
      evaluations of peak extraction algorithms, sample surface height is generally
      assumed to be zero, and only sampling-noise-induced peak extraction uncertainty
      was analyzed. Here we propose a sample surface-height-dependent (SHD) evaluation
      model that takes the combined considerations of sample surface height and noise
      for comparisons of algorithms' performances. Monte Carlo simulations were first
      conducted on the centroid algorithm and several nonlinear fitting algorithms such
      as the parabola fitting algorithm, Gaussian fitting algorithm, and sinc2 fitting
      algorithm. Subsequently, the evaluation indicators, including mean peak
      extraction error and mean uncertainty were suggested for the algorithms'
      performance ranking. Finally, experimental verifications of the SHD model were
      carried out using a fiber-based chromatic confocal system. From our simulations
      and experiments, we demonstrate that sample surface height is a critical
      influencing factor in peak extraction computation in terms of both the accuracy
      and standard deviations. Compared to the conventional standard uncertainty
      evaluation model, our SHD model can provide a more comprehensive characterization
      of peak extraction algorithms' performance and offer a more flexible and
      consistent reference for algorithm selection.

PMID- 30117891
TI  - Spatially correlated coherent diffractive imaging method.
AB  - Coherent diffractive imaging (CDI) is a lensless, high-resolution imaging method
      that is currently under rapid development by using X-rays, visible light, or
      electrons. However, its inherent ambiguities and the need of a priori knowledge
      about objects are limiting applications based on this method. By combining a
      conventional CDI method with the basic idea of ptychography, the method of
      spatially correlated CDI, a method fit for multiple sample imaging in single-shot
      mode, is proposed to enhance the robustness of CDI. In this method, a strong
      spatial relevancy is built by introducing the same region into each sample, which
      establishes a strong real-space constraint for image reconstruction. Both
      simulations and visible-light experiments demonstrated the good imaging quality
      and robustness of this method, which does not need tight supports.

PMID- 30117892
TI  - Rayleigh backscattered radiation produced by an arbitrary incident mode in
      multimode optical fibers.
AB  - The recently developed diffraction technique of analytical investigation of the
      Rayleigh backscattering produced by an incident fundamental mode in a multimode
      optical fiber with an arbitrary refractive index profile is generalized to admit
      an arbitrary incident mode, either radial or azimuthal. The relative powers of
      all backscattered modes are determined with explicit formulas via the properly
      normalized transverse distributions of the incident and backscattered mode fields
      within the fiber cross section. The regularities conditioned by azimuthal indices
      are expressed via a universal set of coefficients, and dependences on the radial
      mode indices are estimated numerically. Excitation coefficients are shown to be
      symmetrical for any pair of incident and backscattered modes.

PMID- 30117893
TI  - Compact portable laser system for mobile cold atom gravimeters.
AB  - We have designed and realized a compact portable laser system for high
      sensitivity mobile cold atom interferometers. The laser system is mounted on a
      single module with dimensions of 45  cm*45  cm*16  cm and emits lights directly
      on up to 13 fiber ports for a two-dimensional magneto-optical trap, atom
      fountain, Raman transition, and normalized detection. A double-sided optical
      structure and mounts without kinematic adjustment are designed to achieve high
      level integration and stability. The laser system is applied to a mobile atom
      gravimeter and achieves a sensitivity of 28  MUGal/Hz1/2. Experiencing 1200-km
      long truck transportation, the laser system could be restored to good operating
      status without internal realignment.

PMID- 30117894
TI  - Regularized slanted-edge method for measuring the modulation transfer function of
      imaging systems.
AB  - The slanted-edge method for modulation transfer function (MTF) measurement uses
      edge target images whose gray values are often affected by noise and other
      factors, decreasing its accuracy. We first analyze the ill-posedness in the edge
      spread function (ESF) regression caused by noise. Second, we propose a
      regularized slanted-edge method to solve this problem by incorporating a Tikhonov
      regularization term. Combined with varying precision weights, the ESF is solved
      using the variational principle, and the MTF is estimated using the regularized
      ESF. The regularized slanted-edge method is verified for Gaussian, gamma, and
      Rayleigh noise. The results show that our method improves the accuracy by 0.01
      9.02% and 4.33% on average. The proposed method is more robust to noise and
      accurate than the slanted-edge method.

PMID- 30117895
TI  - Sky brightness and color measurements during the 21 August 2017 total solar
      eclipse: comment.
AB  - While observing the 21 August 2017 total solar eclipse from Shoshoni, Wyoming,
      the author briefly witnessed an annulus of red light 2 degrees  to 3 degrees 
      from the center of the totally eclipsed sun. The author had no prior knowledge of
      this phenomenon, thus reducing the chances of observational bias. A simple
      experiment suggests that the phenomenon may not be the result of an afterimage
      illusion produced by observing the eclipse through binoculars. The results of
      these observations appear to support the CCD color measurements of the sky during
      the same eclipse observed from Esterbrook, Wyoming, by Bruns and Bruns [Appl.
      Opt.57, 4590 (2018)APOPAI0003-693510.1364/AO.57.004590].

PMID- 30117896
TI  - Photothermal determination of the angular dependence of emissivity.
AB  - A method for directional emissivity determination by measurement of absorption
      through a photothermal effect is described. The experimental results found for
      Au, Al, and graphite show good agreement with the theoretical prediction of the
      electromagnetic theory. It is shown as well that complex refractive indices can
      be determined by fitting angular absorption data with theory.

PMID- 30117897
TI  - Experimental characterization and modeling of optical tweezer particle handling
      dynamics.
AB  - We report a new framework for a quantitative understanding of optical trapping
      (OT) particle handling dynamics. We present a novel three-dimensional particle
      based model that includes optical, hydrodynamic, and inter-particle forces. This
      semi-empirical colloid model is based on an open-source simulation code known as
      LAMMPS (large-scale atomic/molecular massively parallel simulator) and properly
      recapitulates the full OT force profile beyond the typical linear approximations
      valid near the trap center. Simulations are carried out with typical system
      parameters relevant for our experimental holographic optical trapping (HOT)
      system, including varied particle sizes, trap movement speeds, and beam powers.
      Furthermore, we present a new experimental method for measuring both the stable
      and metastable boundaries of the optical force profile to inform or validate the
      model's underlying force profile. We show that our framework is a powerful tool
      for accurately predicting particle behavior in a practical experimental OT setup
      and can be used to characterize and predict particle handling dynamics within any
      arbitrary OT force profile.

PMID- 30117898
TI  - Polarization-induced distortion effects on the information rate in single-mode
      fibers.
AB  - In this paper, we examine information theoretical properties of single-mode
      fibers in the presence of polarization-induced distortion effects. We derive some
      capacity results and further obtain several nonergodic achievable rates. In this
      work, however, mostly linear distortions are considered. Since polarization
      dependent loss (PDL) is a nonunitary phenomenon, information rate loss caused by
      PDL is fundamentally inevitable. Interestingly, it is shown that in the presence
      of channel state information at the transmitter, PDL can increase the capacity in
      some scenarios. We analytically found also that the highest average capacity
      improvement from the knowledge of PDL at the transmitter is equal to the mean PDL
      of the link, and this benefit vanishes at high signal-to-noise ratio. In order to
      achieve the ergodic capacity, it is established that sending uncorrelated
      Gaussian signals with equal power via both polarizations is the optimum transmit
      strategy. As it turns out from the results, perhaps counterintuitively, in the
      presence of PDL, polarization mode dispersion (PMD) always improves the maximum
      outage rate; however, the PMD impact on the maximum throughput and the maximum
      two-layer expected rate is trivial. Finally, an extension to the simple Gaussian
      noise model of fiber nonlinearity is explored. All theoretical results are
      illustrated by numerical simulations.

PMID- 30117899
TI  - Wrapping-free numerical refocusing of scalar electromagnetic fields.
AB  - Numerical refocusing in any plane is one powerful feature granted by measuring
      both the amplitude and the phase of a coherent light beam. Here, we introduce a
      method based on the first Rytov approximation of scalar electromagnetic fields
      that (i) allows numerical propagation without requiring phase unwrapping after
      propagation and (ii) limits the effect of artificial phase singularities that
      appear upon numerical defocusing when the measurement noise is mixing with the
      signal. We demonstrate the feasibility of this method with both scalar
      electromagnetic field simulations and real acquisitions of microscopic biological
      samples imaged at high numerical aperture.

PMID- 30117900
TI  - Single-angle reflectance spectroscopy to determine the optical constants n and k:
      considerations in the far-infrared domain.
AB  - Single-angle infrared (IR) reflectance spectroscopy is a proven and effective
      method for determining the complex optical constants n and k of condensed matter.
      The modern method uses a Fourier transform IR spectrometer to record the
      quantitative reflectance R(nu) spectra followed by application of the Kramers
      Kronig transform (KKT) to obtain the complex optical constants. In order to carry
      out the KKT, it is essential to measure the reflectance spectra to as high and
      low a frequency (wavenumber) as possible. Traditionally, the reflectance spectra
      of solid specimens consist of large (typically>10  mm diameter) polished single
      crystal faces free of defects or voids. The requirement of a large polished face,
      however, is not a realistic expectation for many synthetic, geologic, or rare
      specimens where the size is usually small and the morphology can vary. In this
      paper we discuss several improvements and considerations to both the hardware and
      far-IR measurement protocols that lead to more accurate R(nu) values and thus to
      more accurate n/k values, especially for small (millimeter-sized) specimens where
      the R(nu) spectrum is concatenated from multiple independent R(nu) spectra from
      overlapping hardware/spectral domains. Specifically, the improved hardware and
      analyses introduced here include the following: (1) providing a set of far-IR
      calibration standards; (2) custom-designing and manufacturing low reflectivity,
      stray-light reducing sample masks for small specimens; (3) minimizing stray light
      interaction between the sample mask, the interferometer Jacquinot stop, and the
      detector; (4) optimizing the methods to "splice" together the spectra from
      independent domains; (5) discussing what methods one can use to obtain or
      calculate the important R(0  cm-1) value; (6) using a quartic relationship to
      extrapolate from the measured R data to R(0); and (7) accounting for the limiting
      effects of diffraction for the spot size at the sample mask and detector for
      millimeter-sized specimens, especially at the very long wavelengths. These seven
      considerations are all highly interconnected and are discussed in turn, as well
      as their strong interdependencies. This paper presents a holistic approach for
      determining reliable n/k values of millimeter-sized samples using single-angle
      reflectance in the mid- and far-IR.

PMID- 30117901
TI  - Holographic fabrication of graded photonic super-quasi-crystals with multiple
      level gradients.
AB  - Photonic quasi-crystals and photonic crystals with certain degrees of disorder
      can have a broadband light-matter interaction. In this paper, we present the
      holographic fabrication of graded photonic super-quasi-crystals through pixel-by
      pixel phase pattern engineering using a spatial light modulator. Using the same
      phase pattern arranged in a decagon, we have fabricated graded photonic super
      quasi-crystals with five-fold symmetry and multiple levels of gradients and
      graded photonic super-crystals with rectangular unit super-cells, depending on
      the Fourier filter. Although a certain degree of disorder was incorporated in the
      quasi-crystals, we still observed the golden ratio in the diameters of the
      diffraction rings of the fabricated quasi-crystals, indicating five-fold
      symmetry. Using direct pixel-by-pixel phase engineering, the same laser
      projection system, consisting of an integrated spatial light modulator and a
      reflective optical element, can be used for the fabrication of graded photonic
      super-crystals with various symmetries. The multi-level gradient effects on the
      optical properties of an organic light-emitting diode were simulated. When the
      cathode of an organic light-emitting device is patterned in the graded photonic
      super-crystals, a light extraction efficiency up to 76% in the visible range can
      be achieved.

PMID- 30117902
TI  - On-orbit characterization of the VIIRS solar diffuser and attenuation screens for
      NOAA-20 using yaw measurements.
AB  - The follow-up visible infrared imaging radiometer suite (VIIRS) housed in the
      NOAA-20 satellite and the first of four in the NOAA Joint Polar Satellite System
      satellite series, was launched on 18 November 2017. The on-orbit satellite yaw
      maneuver operation was carried out on 25-26 January 2018 over 15 scheduled orbits
      to obtain responses of the reflective solar bands (RSBs) and the solar diffuser
      stability monitor (SDSM) over a specified angular range. This paper presents a
      comprehensive analysis of the yaw measurements that characterizes the three
      required input functions for the standard on-orbit RSB calibration pipeline. The
      characterization functions of the product of the bidirectional reflectance
      factors (BRFs) of the solar diffuser (SD) with the vignetting function (VF) of
      the SD screen (SDS), dubbed the BRF-VF-products (BVPs), are derived for the two
      required outgoing directions from the SD, one set for the RSB BVPs from the SD to
      the rotation telescope assembly that directs light to the RSBs, and another set
      for the SDSM BVPs for the outgoing direction from the SD to the SDSM. The VFs for
      the attenuation screen placed in front of the Sun-view port, the Sun-view screen
      (SVS), are analyzed as a set of standalone functions to characterize the direct
      solar illumination reaching the SDSM through the SVS, but the complexity of their
      non-smooth two-dimensional dependence requires an additional direct treatment in
      the derivation of the degradation of the SD, the H-factors. The results for the
      RSB BVPs, SDSM BVPs, and the SVS VFs are presented and discussed, and further
      applied to derive the early-mission performance of H-factors and the RSB
      calibration coefficients, or F-factors. The overall results of the H-factors and
      F-factors showing smooth trends with negligible residuals indicate that the
      derived BVP functions and the SVS VFs have been accurately characterized or
      treated, and are ready for use for the standard on-orbit RSB calibration of NOAA
      20 VIIRS.

PMID- 30117903
TI  - Design of an atom source collimator for a compact frequency-stabilized laser.
AB  - A concise laser system for optically pumped cesium beam clocks is presented. The
      laser's frequency is locked by a fluorescence signal, produced by the interaction
      between a cesium atomic beam and laser. A cesium oven with a longer atom source
      collimator, formed by an array of channels, was used to reduce the divergence
      angle of the cesium atomic beam. The size of the cesium source collimator is 4 
      mm*0.6  mm, and the cesium expenditure rate is 2.4*10-1  g per year. A dense
      cesium atomic flux was used to interact with the laser to generate a fluorescence
      signal when the oven heating temperature is not too high. The cesium beam tube
      could have a longer lifetime. The optical structure of the laser system is
      compact. The measured frequency stability of the laser is ~4*10-11 at 10,000 s
      when the laser frequency is locked in the F=4->F'=5 transition of the cesium D2
      line. The design of an atom oven and atom source may be used in other atomic beam
      clocks to improve their performance.

PMID- 30117904
TI  - Measuring refractive index of glass by using speckle.
AB  - A method to measure the refractive index of an optically flat, regularly shaped
      slab of glass using speckle correlation-based techniques is reported. The
      intensity of the diffraction field of the diffuser is captured by a CCD both with
      and without the glass present. As the position of the peak correlation
      coefficient is quantitatively related to the change in optical path length
      arising due to the presence of the glass, the refractive index of the glass can
      be evaluated by cross-correlating the two captured images. The theoretical
      correlation function that describes the effects of such an optical path length
      change is discussed, and the resulting speckle decorrelation function derived.
      Two glass samples are measured to demonstrate the accuracy and robustness of the
      proposed technique.

PMID- 30117905
TI  - Thermally stable hybrid cavity laser based on silicon nitride gratings.
AB  - In this paper, we show the experimental results of a thermally stable Si3N4
      external cavity (SiN EC) laser with high power output and the lowest SiN EC laser
      threshold to our knowledge. The device consists of a 250 MUm sized reflective
      semiconductor optical amplifier butt-coupled to a passive chip based on a series
      of Si3N4 Bragg gratings acting as narrow reflectors. A threshold of 12 mA has
      been achieved, with a typical side-mode suppression ratio of 45 dB and measured
      power output higher than 3 mW. Furthermore, we achieved a mode-hop free-lasing
      regime in the range of 15-62 mA and wavelength thermal stability up to 80 degrees
      C. This solves the challenges related to cavity resonances' thermal shift and
      shows the possibility for this device to be integrated in dense wavelength
      division multiplexing (WDM) and heat-intensive optical interconnects
      technologies.

PMID- 30117906
TI  - Feasibility of correlation mapping optical coherence tomography angiographic
      technique using a 200  kHz vertical-cavity surface-emitting laser source for in
      vivo microcirculation imaging applications.
AB  - Optical coherence tomography (OCT) angiography is a well-established in vivo
      imaging technique to assess the overall vascular morphology of tissues and is an
      emerging field of research for the assessment of blood flow dynamics and
      functional parameters such as oxygen saturation. In this study, we present a
      modified scanning-based correlation mapping OCT using a 200 kHz high-speed swept
      source OCT system operating at 1300 nm and demonstrate its wide field-imaging
      capability in ocular angiographic studies.

PMID- 30117907
TI  - Optics in Ireland: introduction to the feature issue.
AB  - This feature issue provides a snapshot of some of the applied optics and
      photonics related research and development activities currently taking place
      across Ireland. The issue contains some thirty papers, including contributions
      from universities and institutes of technology research groups, state research
      laboratories and institutes, and commercial companies.

PMID- 30117908
TI  - Multicomponent analysis using a confocal Raman microscope.
AB  - Measuring the concentration of multiple chemical components in a low-volume
      aqueous mixture by Raman spectroscopy has received significant interest in the
      literature. All of the contributions to date focus on the design of optical
      systems that facilitate the recording of spectra with high signal-to-noise ratio
      by collecting as many Raman scattered photons as possible. In this study, the
      confocal Raman microscope setup is investigated for multicomponent analysis.
      Partial least-squares regression is used to quantify physiologically relevant
      aqueous mixtures of glucose, lactic acid, and urea. The predicted error is 17.81
      mg/dL for glucose, 10.6 mg/dL for lactic acid, and 7.6 mg/dL for urea, although
      this can be improved with increased acquisition times. A theoretical analysis of
      the method is proposed, which relates the numerical aperture and the
      magnification of the microscope objective, as well as the confocal pinhole size,
      to the performance of the technique.

PMID- 30117909
TI  - Serialized holography for brand protection and authentication.
AB  - The problems presented by counterfeit products and documentation are discussed.
      Limitations of existing holograms for anti-counterfeit applications are
      described. We describe the advantages of full holographic serialization and the
      requirements in terms of materials and techniques for mass production of true
      serialized holograms. These requirements having been met, we report for the first
      time the mass production of fully serialized holograms. The novelty of the
      approach consists of the direct use of the product manufacturer's information as
      the object in a holographic recording system along with a self-processing
      photopolymer and modular optical system to facilitate mass production of truly
      serialized volume holograms. Various types of serialized holograms for overt and
      covert authentication are described. We discuss briefly the application of
      Optrace's manufacturing methods for future generation holographic devices.

PMID- 30117910
TI  - Holographic characterization of diffraction grating modulation in photopolymers.
AB  - In general, the holographic grating refractive index profiles in photopolymer
      materials are not identical to the exposing pattern. During exposure, high
      harmonics of the fundamental refractive index period are generated within the
      layer volume. A set of equations to calculate the amplitudes of the higher
      harmonics of refractive index induced in the grating is introduced. Then, an
      algorithm involving the use of the 3D nonlocal photopolymerization-driven
      diffusion model is presented and applied to calculate the resulting grating
      diffraction efficiencies. The experimental observation that the grating
      diffraction efficiency cannot reach the theoretical maximum value (etamax=100%)
      and that, in the case of over-modulation, the minimum value (etamin=0%) is also
      never achieved, are explained theoretically. The predictions of the simulations
      are also fit to experimental data for an acrylamide/polyvinyl alcohol
      photopolymer material with good agreement being achieved.

PMID- 30117911
TI  - Estimating axial resolution with diffraction theory.
AB  - Depth estimation is a classic machine vision and image processing problem aiming
      at mapping the distances of objects from the camera. The accuracy of this depth
      map depends on the axial resolution achieved by the system, which is usually
      estimated using geometrical optics theory. This paper proposes a novel formula
      using diffraction theory. A comparison with the geometrical approach for
      estimating the axial resolution is provided, and results for several simulations
      are discussed.

PMID- 30117912
TI  - Characterization of an amplified piezoelectric actuator for multiple-reference
      optical coherence tomography.
AB  - The characterization of an amplified piezoelectric actuator (APA) as a new axial
      scanning method for multiple-reference optical coherence tomography (MR-OCT) is
      described. MR-OCT is a compact optical imaging device based on a recirculating
      reference-arm-scanning optical delay using a partial mirror that can enhance the
      imaging depth range by more than 10 times the reference mirror's scanning
      amplitude. The scanning amplitude of the used APA was varied between 30 MUm and
      250 MUm, depending on the scanning frequency of between 0.8 kHz and 1.2 kHz. A
      silver-coated miniature mirror was attached to the APA via ultraviolet-cured
      optical adhesive, and the light source was a super-luminescent diode with 1310 nm
      center wavelength and 56 nm bandwidth. The sensitivity was measured with and
      without the partial mirror in the reference delay line as a function of scan
      speed, frequency, and range, therefore providing results for MR-OCT and TD-OCT
      modes. It was found that the APA provides more than twice the mechanical scanning
      range compared to other opto-mechanic actuators, but results indicate degradation
      of signal-to-noise ratio and sensitivity at larger imaging depths. In conjunction
      with MR-OCT, the scan range of maximum 200 MUm can be enhanced up to 1-1.5 mm by
      using a reduced amount of orders of reflections, which could be of interest to
      increase sensitivity in the future.

PMID- 30117913
TI  - High power narrow linewidth discrete mode laser diode integrated with a curved
      semiconductor optical amplifier emitting at 2051  nm.
AB  - We report on a 2.051 MUm InxGaAs/InP-based discrete mode laser diode
      monolithically integrated with a curved tapered semiconductor optical amplifier
      for CO2 sensing applications. At a heat-sink temperature of 0 degrees C, the
      laser emits a record InP value of more than 35 mW continuous-wave output power in
      a single longitudinal mode.

PMID- 30117914
TI  - Intensity-dependent nonlinear refraction of antimonene dispersions in the visible
      and near-infrared region.
AB  - Antimonene is a stable 2D allotrope of antimony that is predicted to have a
      direct bandgap, high third-order optical nonlinear susceptibility, and high
      electron mobility. These properties give it huge potential applications in
      photonics and optoelectronics. However, the nonlinear refractive response of
      antimonene dispersions, which is the key to nonlinear refraction-based devices,
      has not been fully investigated. In this work, we investigated the optical
      nonlinearities of the antimonene dispersions by spatial self-phase modulation
      (SSPM) at 405, 785, and 1064 nm wavelengths. The SSPM rings were observed at 405,
      785, and 1064 nm, implying the broadband nonlinear optical response of antimonene
      dispersions from visible to near-infrared. The effective nonlinear refractive
      index, n2, and the third-order susceptibility, chi(3), of the antimonene
      dispersion were measured to be ~10-5  cm2 W-1 and ~10-8  esu, respectively.
      Furthermore, the nonlinearity of antimonene was demonstrated to be tuneable by
      the laser intensities. The relative change of the nonlinear refractive index,
      Deltan2e/n2e, was observed to range from 14% to 63% for different intensities.
      Our results will be helpful for the photonic applications of antimonene in a
      broadband wavelength range, such as optical modulators and switchers.

PMID- 30117915
TI  - Phase randomization for spatiotemporal averaging of unwanted interference effects
      arising from coherence.
AB  - An approach to the reduction of unwanted interference effects, such as speckle
      and inhomogeneity, is to generate sequences of uncorrelated effects over the
      integration period of the sensor such that they are averaged. A moving diffuser
      is typically used. An innovative deformable mirror technology is presented as an
      alternative. Through phase randomization it achieves dynamic divergence of
      illumination without diffraction losses. It is shown to offer a unique
      combination of advantages over moving diffusers, including optical efficiency,
      speed, size, and reliability. Various applications are discussed.

PMID- 30117917
TI  - Laser beam imaging via multiple mode operations of the extreme dynamic range CAOS
      camera.
AB  - Demonstrated for the first time, to the best of our knowledge, is laser beam
      imaging via multiple mode operations of the digital micro-mirror device-based
      coded access optical sensor (CAOS) camera. Specifically, outlined are novel modes
      of software programmable CAOS imaging, which include the time division multiple
      access (TDMA) mode, the code division multiple access (CDMA) mode, the CDMA-TDMA
      mode, the frequency division multiple access (FDMA)-TDMA mode, the frequency
      modulation (FM)-CDMA-TDMA mode, FM-TDMA mode, and the FDMA-CDMA-TDMA mode.
      Engagement of FDMA and CDMA modes enables simultaneous multi-pixel improved
      signal-to-noise ratio photo detection, while use of TDMA prevents optical point
      detector saturation. The use of the FDMA and FM modes creates high digital signal
      processing gain via temporal spectrum analysis to produce extreme dynamic range
      pixel-specific imaging. Using an un-attenuated 633 nm He-Ne laser near-Gaussian
      focusing beam, experimentally acquired are 13.68 MUm spatial resolution laser
      beam map CAOS images with dynamic ranges of 44.78 dB, 45.28 dB, 83.90 dB, and
      94.9 dB for the TDMA, CDMA, FM-CDMA-TDMA, and FM-TDMA modes, respectively. The FM
      TDMA mode with its extreme dynamic ranging CAOS pixel-mapping capability
      experimentally measures the non-Gaussian spatially oscillatory irradiance
      behavior predicted by Huygens-Fresnel diffraction theory. The demonstrated CAOS
      camera through software control allows high-flexibility, robust imaging of laser
      beams across different wavelength bands with widely varying beam irradiance
      levels and spatial signatures, thus empowering optical system designers to match
      overall system requirements that are highly dependent on accurate and reliable
      laser beam metrology.

PMID- 30117916
TI  - Advancing Raman microspectroscopy for cellular and subcellular analysis: towards
      in vitro high-content spectralomic analysis.
AB  - In the confocal mode, Raman microspectroscopy can profile the biochemical content
      of biological cells at a subcellular level, and any changes to it by exogenous
      agents, such as therapeutic drugs or toxicants. As an exploration of the
      potential of the technique as a high-content, label-free analysis technique, this
      report reviews work to monitor the spectroscopic signatures associated with the
      uptake and response pathways of commercial chemotherapeutic agents and polymeric
      nanoparticles by human lung cells. It is demonstrated that the signatures are
      reproducible and characteristic of the cellular event, and can be used, for
      example, to identify the mode of action of the agent as well as the subsequent
      cell death pathway, and even mechanisms of cellular resistance. Data mining
      approaches are discussed and a spectralomics approach is proposed.

PMID- 30117918
TI  - Label-free multimodal coherent anti-Stokes Raman scattering analysis of
      microparticles in unconstrained microfluidics.
AB  - Fast, label-free optical identification and quantification of biomolecules and
      other relevant biological materials in microfluidic devices and the vascular
      system will play a major role in liquid biopsy and related diagnoses. An optical
      microscope probing simultaneously non-linear coherent anti-Stokes Raman
      scattering (CARS) and linear scattering (LS) was used to probe microparticles in
      aqueous solutions flowed unconstrained in microfluidic channels. Despite the
      optical complexity of these systems, where out-of-focus microparticles randomly
      impede CARS and LS, and where water CARS generates a substantial background, we
      demonstrate that in-focus microparticles can be individually and unambiguously
      detected when CARS and LS are co-analyzed. The ability to chemically discriminate
      microscale features in optically realistic flows supports the relevance of
      multimodal CARS platforms for liquid biopsy.

PMID- 30117919
TI  - Dynamics of two identical mutually delay-coupled semiconductor lasers in photonic
      integrated circuits.
AB  - We theoretically investigate a system of two mutually delay-coupled semiconductor
      lasers, in a face to face configuration for integration in a photonic integrated
      circuit. This system is described by single-mode rate equations, which are a
      system of delay differential equations with one fixed delay. Several bifurcation
      scenarios involving multistabilities are presented, followed by a comprehensive
      frequency analysis of the symmetric and symmetry-broken, one-color and two-color
      states.

PMID- 30117920
TI  - Stabilization of self-mode-locked QDash lasers subject to simultaneous continuous
      wave optical injection and optical feedback.
AB  - In this paper, we report stabilization of self-mode-locked two-section quantum
      dash lasers on the widest range of delay using simultaneous optical injection and
      optical feedback. With continuous-wave optical injection, various wavelengths
      spanning a range from 1568 to 1578 nm were investigated and optimum wavelengths
      (1571.210 to 1572.710) yielding the narrowest RF linewidth and reduced timing
      jitter of slave laser were identified. In addition, the dependence of RF
      linewidth and pulse repetition rate on injected wavelength was further explored.
      Our results indicate that simultaneous optical feedback and optical injection
      significantly improves the RF linewidth across the widest delay range compared to
      optical feedback alone. Under fully resonant feedback and optimum injection
      parameters, a minimum RF linewidth of 1 kHz (instrument limited) was achieved
      with simultaneous optical injection plus optical feedback, which was >2* lower
      than optical feedback alone and more than 100* lower than free-running. This
      stabilization technique is implemented in an all-optical arrangement without
      optical/electrical conversion, which is ideal for high-repetition-rate devices
      and photonic integration.

PMID- 30117921
TI  - Surface plasmon propagation enhancement via bowtie antenna incorporation in Au
      mica block waveguides.
AB  - The optimum geometry for waveguide propagation was determined by comparing bowtie
      and semicircle antenna cuts to a standard plain waveguide with a 635 nm laser.
      The results of both experimental data and COMSOL simulations proved that the
      bowtie antenna increased waveguide output in comparison to the plain waveguide
      with the semicircle pattern showing no enhancement. It was also determined that
      the propagation was highest when the polarization direction of the laser was
      perpendicular to the direction of the waveguide for all patterns, while
      polarization along the propagation direction led to little or no output in all
      antenna and plain waveguide cases. The waveguide output of the bowtie antenna and
      plain structures was then measured using a tunable laser for wavelengths from 570
      nm to 958 nm under both parallel and perpendicular polarization conditions. The
      results indicated that the bowtie antenna performed better over the entire range
      with an average increase factor of 2.12+/-0.40 over the plain waveguide pattern
      when perpendicularly polarized to the waveguide direction, and 1.10+/-0.48 when
      parallel. The measured values indicate that the structure could have applications
      in broadband devices.

PMID- 30117922
TI  - Nonpupil adaptive optics for visual simulation of a customized contact lens.
AB  - We present a method for determining the deformable mirror profile to simulate the
      optical effect of a customized contact lens in the central visual field. Using
      nonpupil-conjugated adaptive optics allows a wider field simulation compared to
      traditional pupil-conjugated adaptive optics. For a given contact lens, the
      mirror shape can be derived analytically using Fermat's principle of the
      stationary optical path or numerically using optimization in ray-tracing
      programs. An example of an aspheric contact lens simulation is given to
      illustrate the method, and the effect of eye misalignment with respect to the
      deformable mirror position is investigated. The optimal deformable mirror
      conjugation position is found to be near the posterior corneal surface. Chromatic
      aberration analysis is also presented, and our findings indicate that the
      polychromatic simulation quality is similar to that of the monochromatic case,
      even though the mirror is a reflective component. The limitations of a single
      continuous surface deformable mirror to mimic a contact lens are outlined, with
      some recommendations for improving the quality of simulation.

PMID- 30117923
TI  - Key enabling technologies for optical communications at 2000  nm.
AB  - This paper discusses the potential for opening a new wavelength window at the 2
      MUm waveband for optical communications, showing current limitations of the
      system's performance. It focuses on novel results for key enabling technologies,
      including the analysis of laser injection locking at this waveband, an improved
      responsivity for bulk and strained InGaAs edge-couple detectors, and also an
      increased gain profile for thulium-doped fiber amplifiers.

PMID- 30117924
TI  - Tunable thermally induced gradient index for extended depth of field.
AB  - Extended depth of field (EDoF) imaging remains desirable in the consumer market
      due to its reduced cost through omission of refocusing hardware. This paper
      describes the study of a heated plastic plate and its effect on EDoF imaging. It
      is shown that the depth of field of an imaging device can be extended by heating
      either the periphery or core of a homogeneous element-solving the heat equation
      for a parallel plate generates a radial gradient index structure, which can be
      modeled in Zemax ray-tracing software. For an F/2 system with the dimensions of a
      typical mobile-device camera, the heating arrangement shifts the peak value of
      the modulation transfer function (MTF) at Nyquist/2 from object distance 1350 to
      750 mm. This study suggests the possibility of a fixed-focus camera with distinct
      modes: a "high-quality" mode operational over the standard depth of field when
      the plate is not heated; a "macro" mode triggered by heating the plate periphery;
      and a "wide-focus" mode triggered by heating the lens core. Importantly, the
      reduction in MTF generally associated with EDoF solutions is not present when the
      plate is unheated. The plate, having no optical power when unheated, can be added
      to existing off-the-shelf lens designs. Such a heating arrangement could provide
      a very-low-cost refocusing alternative where moving parts are not desirable.

PMID- 30117925
TI  - Self-written waveguides in photopolymer.
AB  - Self-written waveguide (SWW) trajectories fabricated inside a dry photopolymer
      bulk material, acrylamide/polyvinyl alcohol (AA/PVA), are studied. Their
      production using both Gaussian and Laguerre-Gauss exposing (writing) light beams,
      output from optical fibers, is explored. The formation of the primary and
      secondary eyes is also discussed. Furthermore, the interactions that take place
      when two counterpropagating beams pass through the photopolymer material (both
      Gaussian and Laguerre-Gauss) are examined. In all cases experimental and
      theoretical results are presented. Good agreement between the predictions of the
      proposed model and experimental observations are demonstrated.

PMID- 30117926
TI  - Numerical investigation of a feed-forward linewidth reduction scheme using a mode
      locked laser model of reduced complexity.
AB  - We provide numerical verification of a feed-forward, heterodyne-based phase noise
      reduction scheme using single-sideband modulation that obviates the need for
      optical filtering at the output. The main benefit of a feed-forward heterodyne
      linewidth reduction scheme is the simultaneous reduction of the linewidth of all
      modes of a mode-locked laser (MLL) to that of a narrow-linewidth single
      wavelength laser. At the heart of our simulator is an MLL model of reduced
      complexity. Importantly, the main issue being treated is the jitter of MLLs and
      we show how to create numerical waveforms that mimic the random-walk nature of
      timing jitter of pulses from MLLs. Thus, the model does not need to solve
      stochastic differential equations that describe the MLL dynamics, and the model
      calculates self-consistently the line-broadening of the modes of the MLL and
      shows good agreement with both the optical linewidth and jitter. The linewidth
      broadening of the MLL modes are calculated after the phase noise reduction scheme
      and we confirm that the phase noise contribution from the timing jitter still
      remains. Finally, we use the MLL model and phase noise reduction simulator within
      an optical communications system simulator and show that the phase noise
      reduction technique could enable MLLs as optical carriers for higher-order
      modulation formats, such as 16-state and 64-state quadrature amplitude
      modulation.

PMID- 30117927
TI  - Development of a prototype active optics system for future space telescopes.
AB  - It is envisaged that future large space telescopes will be lightweight and employ
      active optics to maintain optical quality throughout the mission lifetime. We
      have proposed a 4 m, two-mirror space telescope with an active optics system
      based on reimaging the telescope primary mirror onto a small active mirror (110
      mm optical pupil). Using Zemax, we demonstrate the feasibility of using this
      mirror to correct low-order Zernike aberrations and show that the aberration is
      well corrected across the 2.5 arcmin field of the telescope, operating at 0.55
      MUm. We describe the modeling carried out to develop the active mirror design.
      Using end-to-end modeling, a 25-actuator mirror with polar actuator geometry, and
      a ratio of mechanical to optical pupil diameter of 2 has been chosen. A single
      actuator prototype has been manufactured and used to test stroke, linearity, and
      hysteresis. Finally, we describe the design of a laboratory breadboard that will
      image phase screens onto an exact replica of the space active mirror and show the
      results of measuring the phase screen accuracy.

PMID- 30117928
TI  - Comparison and evaluation of geometric calibration methods for infrared cameras
      to perform metric measurements on a plane.
AB  - Geometric information from infrared images can complement the information about
      the measured infrared radiation. However, this requires geometric camera
      calibration. In this work, three calibration methods for infrared cameras are
      compared: a direct and an iterative estimation of the transformation between
      image and world coordinates and a complete camera calibration method using a
      specifically designed calibration target. The three methods are compared and the
      obtained performance for metric measurements on a plane is evaluated. The results
      indicate acceptable performance in the three cases, with the complete method
      clearly outperforming the two others with an average error of only 0.060 mm,
      which represents 0.08% error of the measured distance.

PMID- 30117929
TI  - Exploiting fusion architectures for multispectral pedestrian detection and
      segmentation.
AB  - Recent research has demonstrated that the fusion of complementary information
      captured by multi-modal sensors (visible and infrared cameras) enables robust
      pedestrian detection under various surveillance situations (e.g., daytime and
      nighttime). In this paper, we investigate a number of fusion architectures in an
      attempt to identify the optimal way of incorporating multispectral information
      for joint semantic segmentation and pedestrian detection. We made two important
      findings: (1) the sum fusion strategy, which computes the sum of two feature maps
      at the same spatial locations, delivers the best performance of multispectral
      detection, while the most commonly used concatenation fusion surprisingly
      performs the worst; and (2) two-stream semantic segmentation without
      multispectral fusion is the most effective scheme to infuse semantic information
      as supervision for learning human-related features. Based on these studies, we
      present a unified multispectral fusion framework for joint training of semantic
      segmentation and target detection that outperforms state-of-the-art multispectral
      pedestrian detectors by a large margin on the KAIST benchmark dataset.

PMID- 30117930
TI  - Noninvasive assessment of skin structure by combined photothermal radiometry and
      optical spectroscopy: coregistration with multiphoton microscopy.
AB  - We are combining two optical techniques, pulsed photothermal radiometry (PPTR)
      and diffuse reflectance spectroscopy (DRS), for noninvasive assessment of the
      structure and composition of human skin in vivo. The analysis involves
      simultaneous multidimensional fitting of the measured PPTR signals and DRS
      spectra with predictions of a numerical model of light transport (Monte Carlo) in
      a four-layer model optical model of human skin, accounting for the epidermis,
      papillary and reticular dermis, and subcutis. The assessed epidermal thickness
      values were tested by coregistration with a multiphoton microscope, which
      provides vertical sectioning capability based on two-photon excited fluorescence
      and second-harmonic generation in selected skin components. The comparison shows
      that these values correspond well to the maximal epidermal thicknesses measured
      in the multiphoton microscopy images, the rete ridges.

PMID- 30117931
TI  - Optimized robotic setup for automated active thermography using advanced path
      planning and visibility study.
AB  - In-line inspection of advanced components remains a challenging task in industry.
      The authors will describe an automated methodology that uses numerical
      simulations to automatically determine the best set of experimental parameters to
      inspect the structure on defects using active thermography. The inspection is
      performed using a robotic arm and advanced path-planning tools to determine the
      optimal positions of the measurement points and excitation points. During the
      path planning, the directional emissivity is considered for the complex surface,
      and a minimization of the amount of measurement points is performed. The
      numerical simulation optimization used a genetic algorithm and spline regression
      model to optimize the heat power, robot speed, camera frame rate, and excitation
      timing to fulfill the automatic inspection.

PMID- 30117932
TI  - Attojoule-efficient graphene optical modulators.
AB  - Electro-optic modulation is a technology-relevant function for signal keying,
      beam steering, or neuromorphic computing through providing the nonlinear
      activation function of a perceptron. With silicon-based modulators being bulky
      and inefficient, here we discuss graphene-based devices heterogeneously
      integrated. This study provides a critical and encompassing discussion of the
      physics and performance of graphene. We provide a holistic analysis of the
      underlying physics of modulators including graphene's index tunability, the
      underlying optical mode, and discuss resulting performance vectors for this novel
      class of hybrid modulators. Our results show that reducing the modal area and
      reducing the effective broadening of the active material are key to improving
      device performance defined by the ratio of energy-bandwidth and footprint. We
      further show how the waveguide's polarization must be in-plane with graphene,
      such as given by plasmonic-slot structures, for performance improvements. A high
      device performance can be obtained by introducing multi- or bi-layer graphene
      modulator designs. Lastly, we present recent results of a graphene-based hybrid
      photon-plasmon modulator on a silicon platform and discuss electron beam
      lithography treatments for transferred graphene for the relevant Fermi level
      tuning. Being physically compact, this 100  aJ/bit modulator opens the path
      towards a novel class of attojoule efficient opto-electronics.

PMID- 30117933
TI  - Performance prediction of p-i-n HgCdTe long-wavelength infrared HOT photodiodes.
AB  - Recently, an enhanced computer program was applied to explain in detail the
      influence of different recombination mechanisms (Auger, radiative, and Shockley
      Read-Hall) on the performance of high-operation-temperature, long-wavelength,
      infrared p-i-n HgCdTe heterojunction photodiodes. It is shown that the photon
      recycling effect drastically limits the influence of radiative recombination on
      the performance of small pixel HgCdTe photodiodes. The computer program is based
      on a solution of the carrier transport equations, as well as the photon transport
      equations for semiconductor heterostructures. Both the distribution of thermal
      carrier generation and recombination rates, and spatial photon density
      distribution in photodiode structures have been obtained. In comparison with two
      previously published papers in the Journal of Electronics Materials [J. Electron.
      Mater.45, 4587 (2016)JECMA50361-523510.1007/s11664-016-4566-6 and J. Electron.
      Mater.46, 6295 (2017)JECMA50361-523510.1007/s11664-017-5736-x], our paper
      provides an additional insight on the ultimate performance of long-wavelength
      infrared, high-operation-temperature HgCdTe arrays with pixel densities that are
      fully consistent with background- and diffraction-limited performance due to
      system optics.

PMID- 30117934
TI  - Molecular vibrations of bisphenol "S" revealed by FTIR spectroscopy and their
      correlation with bisphenol "A" disclosed by principal component analysis.
AB  - Bisphenol "S" (BPS), a common replacement for bisphenol "A" (BPA) after its ban
      in food contact applications, is studied by Fourier transform infrared (FTIR)
      spectroscopy (400-6800  cm-1). Identified molecular vibrations are assigned based
      on density functional theory calculations. As BPS is suspected to be as toxic as
      BPA, principal component analysis is used to find possible correlations among
      their molecular vibrations. We have found frequencies showing a connection
      between these two materials via molecular vibrations, helping not only to
      categorize such materials but also to find the origin of their toxicity.

PMID- 30117935
TI  - Light intensity and FOV-controlled adaptive fluidic iris.
AB  - In this paper, we propose a light intensity and field of view (FOV) controlled
      adaptive fluidic iris. A 90 degrees  twisted-nematic liquid crystal (TNLC) cell
      and two orthogonal polarizers are attached on the substrate. When a voltage is
      applied to TNLC, it can change the phase of the incident light, leading to change
      in the light intensity. A black mask is then placed in the middle of the chamber;
      when changing the hydraulic pressure from the inlet and outlet, the black mask
      can move within the chamber. It is equivalent to changing the iris position along
      the optical axis. The iris, therefore, can control the FOV in an optical system.
      The experiments show that the device can control the light intensity from 100% to
      0% by applying a voltage of 9 V on the TNLC cell. The proposed device can be
      applied in imaging systems and optical attenuators.

PMID- 30117936
TI  - Comparative study between linear and non-linear frequency-modulated pulse
      compression thermography.
AB  - Pulse-compression thermography is an emerging non-destructive technique whose
      effectiveness strictly depends on the choice of the coded excitations used to
      modulate the heating stimulus. In this paper, the features of frequency-modulated
      coded signals, i.e., chirps, have been tested for imaging thin Teflon defects
      embedded within a carbon fiber composite specimen. With the aim of maximizing the
      heat transferred within the sample, the use of several optimized non-linear chirp
      signals has been also investigated and their defect detection capability compared
      in terms of the maximum achievable signal-to-noise ratio.

PMID- 30117937
TI  - Induction thermography of steel coupons with cracks.
AB  - The induction thermography technique was assessed experimentally and numerically
      on notched steel coupons using two coil configurations: straight line and loop
      conditions. The coupons had different lengths of fatigue crack varying from zero
      to 3 mm. The numerical predictions showed that the peak temperature was always
      located at the crack tip or the notch tip position. The loop coil resulted in
      higher temperatures than those of the straight line coil. Results showed that the
      numerical methods effectively supported the application assessment of this
      nondestructive evaluation (NDE) technique for the steel material, but crack
      geometry remains a challenge as the exact shape of a natural crack is typically
      unknown. It is shown that induction thermography can detect a crack as small as 1
      mm in the notched steel coupons. Commentary on the application of the NDE
      technique with the numerical modeling support was provided.

PMID- 30117938
TI  - Quantitative evaluation of active thermography using contrast-to-noise ratio.
AB  - Active thermography is an infrared-based technique for nondestructive testing of
      materials. It often uses advanced evaluation techniques based on temperature
      spatial and temporal changes. Results of active thermography are contrast
      differences, which indicate possible defects in an inspected material. These
      differences cannot be quantified by temperature. This contribution is focused on
      the active thermography results' evaluation parameters and the contrast-to-noise
      ratio method, which can be used for quantitative evaluation of the results.
      Different result interpretation procedures are introduced. The influence of a
      selection method for indication and reference regions and the effect of image
      scaling on inspection results are discussed.

PMID- 30117939
TI  - Monte Carlo ray-trace diffraction based on the Huygens-Fresnel principle.
AB  - The goal of this effort is to establish the conditions and limits under which the
      Huygens-Fresnel principle accurately describes diffraction in the Monte Carlo ray
      trace (MCRT) environment. This goal is achieved by systematic intercomparison of
      dedicated experimental, theoretical, and numerical results. We evaluate the
      success of the Huygens-Fresnel principle by predicting and carefully measuring
      the diffraction fringes produced by both single slit and circular apertures. We
      then compare the results from the analytical and numerical approaches with each
      other and with dedicated experimental results. We conclude that use of the MCRT
      method to accurately describe diffraction requires that careful attention be paid
      to the interplay among the number of aperture points, the number of rays traced
      per aperture point, and the number of bins on the screen. This conclusion is
      supported by standard statistical analysis, including the adjusted coefficient of
      determination, Radj2, the rms deviation, and the reduced chi-square statistic,
      chiv2.

PMID- 30117940
TI  - Nondestructive testing of resistance spot welds using eddy current thermography.
AB  - The paper presents the use of eddy current thermography for detecting cracks in
      resistance spot welds. The sample is a three-sheet stack-up joined together by
      welding spots. Inductive Helmholtz coil is used for heating up the sample, and
      the thermal response of each spot is monitored using a cooled indium antimonide
      camera. The sequence of images captured is processed using the pulsed-phase
      thermography technique. The phase image is completed with a supplementary
      filtering operation to allow outlining defects. The result was confirmed with
      confocal microscopy inspection.

PMID- 30117941
TI  - Accurate and rapid detection of soil and fertilizer properties based on
      visible/near-infrared spectroscopy.
AB  - Accurate information of soil macronutrient contents and fertilizer macronutrient
      contents is the precondition of precision fertilization; however, how to detect
      soil and fertilizer information rapidly, reliably, and inexpensively remains a
      great challenge. Visible and near-infrared (VIS/NIR) diffuse reflectance
      spectroscopy proves to be an effective tool for extensive investigation of soil
      and fertilizer properties. This study first collected many soil and chemical
      fertilizer samples and performed both spectral scanning and chemical analysis.
      During the correlation between the collected VIS/NIR spectra and the measured
      data, different spectral pretreatment, sample selection, and wavelength
      optimization methods were applied for improving the accuracy and robustness of
      the prediction models. After appropriate spectral processing and selection of
      representative samples, both principal component regression and genetic algorithm
      (GA) can adequately reduce the number of variables and pick out the
      characteristic variables, which not only enhanced prediction speed but also
      greatly improved prediction accuracy. In particular, using GA-based models,
      organic matter content (OMC), total N and pH value in soil and N, P, and K
      contents in fertilizer can all be accurately predicted.

PMID- 30117942
TI  - Eddy current pulsed thermography for ballistic impact evaluation in basalt-carbon
      hybrid composite panels.
AB  - In this paper, eddy current pulsed thermography was used to evaluate ballistic
      impact damages in basalt-carbon hybrid fiber-reinforced polymer composite
      laminates for the first time, to our knowledge. In particular, different hybrid
      structures including intercalated stacking and sandwich-like sequences were used.
      Pulsed phase thermography, wavelet transform, principle component thermography,
      and partial least-squares thermography were used to process the thermographic
      data. Ultrasound C-scan testing and X-ray computed tomography were also performed
      for comparative purposes. Finite element analysis was used for validation.
      Finally, an analytical and comparative study was conducted based on signal-to
      noise ratio analysis.

PMID- 30117943
TI  - Wideband infrared trap detector based upon doped silicon photocurrent devices.
AB  - We have designed, fabricated, and measured infrared trap detectors made from
      arsenic-doped silicon (Si:As) blocked impurity band (BIB) photodetectors. These
      trap detectors are composed of two detectors in a wedge geometry, with an
      entrance aperture diameter of either 1 or 3 mm. The detectors were calibrated for
      quantum efficiency against a pyroelectric reference detector using a Fourier
      transform spectral comparator system, and etalon effects and spatial uniformity
      of the traps were also quantified. Measurements of the traps at a temperature of
      10 K show that nearly ideal external quantum efficiency (>90%) can be attained
      over much of the range from 4 to 24 MUm, with significant responsivity from 2 to
      30 MUm. The traps exhibited maximum etalon oscillations of only 2%, which is
      about 10 times smaller amplitude than those of the single Si:As BIB detectors
      measured under similar conditions. Spatial nonuniformity across the entrance
      apertures of the traps was about 1%. The combination of high detectivity,
      wideband wavelength coverage, spectral flatness, and spatial uniformity make
      these trap detectors an excellent reference detector for spectrally resolved
      measurements and radiometric calibrations over the near- to far-infrared
      wavelength range.

PMID- 30117944
TI  - Lock-in and pulsed thermography for solar cell testing.
AB  - Inspection of solar cells is an important part of their production process
      because even small defects can cause a significant drop of a whole photovoltaic
      module performance. LED illuminated lock-in (LEDILIT) and flash-pulse
      thermographic techniques (FPT) were compared in this study. Lock-in methods are
      more commonly used for solar cell inspection. The aim of the study was to
      discover if the FPT is the appropriate method for inspection of defects of
      multicrystalline solar cells. Experimental setup, inspection results, and
      advantages/disadvantages of both methods are presented. It is demonstrated that
      the LEDILIT is the suitable technique for inspection of defects connected with a
      photovoltaic effect. Local shunts, cracks, and artificial laser-made defects were
      detected. Only some of the most significant shunts and laser-made defects were
      identified by the FPT. However, the FPT inspection is much faster than the
      LEDILIT. The FPT was also able to indicate an inhomogeneity at a bottom layer of
      a cell, which was not connected with a photovoltaic effect and not revealed by
      the LEDILIT.

PMID- 30117945
TI  - Deep learning enhancement of infrared face images using generative adversarial
      networks.
AB  - This work presents a deep learning framework based on the use of deep
      convolutional generative adversarial networks (DCGAN) for infrared face image
      super-resolution. We use DCGAN for upscaling the images by a factor of 4*4,
      starting at a size of 16*16 and obtaining a 64*64 face image. Tests are conducted
      using different infrared face datasets operating in the near-infrared (NIR) and
      the long-wave infrared (LWIR) spectrum. We can see that the proposed framework
      performs well and preserves important details of the face. This kind of approach
      can be very useful in security applications where we can scan faces in the crowd
      or detect faces at a distance and upscale them for further recognition through an
      infrared or a multispectral face recognition system.

PMID- 30117947
TI  - IGA-rule 17 for performance estimation of wavelength-extended InGaAs
      photodetectors: validity and limitations.
AB  - A rule of thumb, denoted as IGA-rule 17, has been developed to describe the
      temperature and cutoff wavelength-dependent dark currents of wavelength-extended
      InGaAs photodetectors in a 2-3 MUm band. The validity and limitations of the rule
      are discussed. This rule is intended as an index for device developers to
      evaluate their technologies in processing, a simple tool for device users to
      estimate reachable performance at various conditions in their design, and an
      effective bridge between the two.

PMID- 30117946
TI  - Dependence of temperature and far-field beam quality on substrate thickness of a
      spectral beam combining grating with 13.4  kW/cm2laser irradiation.
AB  - In previous research, the thermal distortion and far-field beam quality of a
      spectral beam combining grating were analyzed by theory and experiment under the
      irradiation of a high-power continuous-wave laser. It was concluded that the
      thermal expansion of the substrate was the main cause of the grating distortion
      and decrease in the beam quality. However, there was no further study to
      determine a method to decrease the heat deposition on the grating surface and far
      field beam quality factor, M2. In this paper, we theoretically simulate the
      influence of the substrate thickness on the temperature field distribution and
      far-field beam quality of a multilayer dielectric grating. An experimental setup
      is proposed to verify the theoretical calculations. The experimental results are
      in good agreement with the calculations. The conclusions indicate that the
      temperature rise of the grating and M2 are effectively reduced by increasing the
      thickness of the substrate.

PMID- 30117948
TI  - Analysis of short wavelength infrared radiation during laser welding of plastics.
AB  - In this paper, a new measurement system and a new approach in calculation for
      infrared (IR) radiation investigation in quasi-simultaneous transmission laser
      welding of plastics are presented. The measurement system is based on a MW/SWIR
      (medium-wave/short-wave IR) camera and optical filters narrowing the spectral
      region to SWIR. The measured signals contain radiation from the melted zone in
      between the semitransparent and absorbing polymers, as well as radiation from the
      surface and interior of the semitransparent polymer. The new calculation approach
      was developed to distinguish between these signals. It is based on simplification
      of the process to two places with two temperatures (surface and molten interface)
      and knowledge of the spectral optical properties of the material, filters, and
      camera response. The results of measurement and calculation for three different
      optical filters and polyoxymethylene samples with two thicknesses are shown and
      discussed. Good agreement is obtained for the calculation variant using normal
      transmissivity of the semitransparent polymer.

PMID- 30117949
TI  - Single-image-based nonuniformity correction of uncooled long-wave infrared
      detectors: a deep-learning approach.
AB  - Fixed-pattern noise (FPN), which is caused by the nonuniform opto-electronic
      responses of microbolometer focal-plane-array (FPA) optoelectronics, imposes a
      challenging problem in infrared imaging systems. In this paper, we successfully
      demonstrate that a better single-image-based non-uniformity correction (NUC)
      operator can be directly learned from a large number of simulated training images
      instead of being handcrafted as before. Our proposed training scheme, which is
      based on convolutional neural networks (CNNs) and a column FPN simulation module,
      gives rise to a powerful technique to reconstruct the noise-free infrared image
      from its corresponding noisy observation. Specifically, a comprehensive column
      FPN model is utilized to depict the nonlinear characteristics of column
      amplifiers in the readout circuit of FPA. A large number of high-fidelity
      training images are simulated based on this model and the end-to-end residual
      deep network is capable of learning the intrinsic difference between undesirable
      FPN and original image details. Therefore, column FPN can be accurately estimated
      and further subtracted from the raw infrared images to obtain NUC results.
      Comparative results with state-of-the-art single-image-based NUC methods, using
      real-captured noisy infrared images, demonstrate that our proposed deep-learning
      based approach delivers better performances of FPN removal, detail preservation,
      and artifact suppression.

PMID- 30117950
TI  - Ray refraction in uniaxial crystals by Fermat's principle.
AB  - Fermat's principle is used to study the refraction of extraordinary rays into and
      out of uniaxial crystals with arbitrary optic axis orientations. The method
      produces direct formulas for the direction cosines of the refracted rays without
      the need of calculating intermediate quantities. The formulas are validated by
      comparing them with previous ray-tracing methods.

PMID- 30117951
TI  - Size effect of WSe2 on red passively Q-switched fiber laser output performance.
AB  - Transition metal dichalcogenides (TMDs) possess a direct bandgap in the visible
      frequency range and can be applied as attractive visible saturable absorbers
      (SAs). In this paper, a new TMDs tungsten selenide (WSe2)-based red Q-switcher is
      fabricated and successfully used for Q-switched pulse generation in a red Pr3+
      doped ZBLAN fiber laser. The passive Q-switching fiber laser at 635.2 nm
      generates a stable pulse with pulse duration of 504 ns and average output power
      of 4.91 mW as well as a tunable pulse repetition rate of 131.9-260.4 kHz.
      Furthermore, the size effect of WSe2 on the 635 nm passive Q-switching output
      performance is also investigated. Our work will provide certain significance for
      the optimization of passive Q-switching red fiber lasers based on TMDs.

PMID- 30117952
TI  - Active depth estimation from defocus using a camera array.
AB  - This paper introduces an active depth estimation method from defocus using a
      camera array. High-frequency phase-shifted sinusoidal fringe patterns are
      projected onto the surface of the object, making low-texture areas of the object
      surface easily distinguishable. Based on the light field measurement captured by
      a 5*5 camera array, a synthetic aperture refocusing of the fringe images can be
      realized after the camera array is properly calibrated and rectified. The fringe
      modulations at different depths are calculated based on the computationally
      refocused images, which are used as depth cues to reconstruct the 3D shape of the
      measured object. We implemented some experiments to verify the effectiveness of
      the proposed method.

PMID- 30117953
TI  - Two-dimensional shape retrieval from the interferometric out-of-focus image of a
      nonspherical particle-Part I: theory.
AB  - Shape is one of the important characteristics of nonspherical particles. Herein,
      the two-dimensional shapes of several micrometer/millimeter-sized particles with
      a variety of geometrical forms are retrieved from simulated interferometric out
      of-focus images using the Hybrid Input-Output algorithm. The particle concerned
      can be either a single particle or a complex particle with separate parts. The
      impact of the axial size of the three-dimensional particle on the retrieval of
      the two-dimensional shape (i.e., the projection of the particle on the image
      sensor) is analyzed, showing that an increase of the axial size increases the
      deviation of low frequencies in the interferometric out-of-focus image and
      eventually degrades the quality of the reconstructed shape. This study
      demonstrates the capability of the interferometric out-of-focus imaging technique
      on shape information retrieval for micrometer/millimeter-sized nonspherical
      particles.

PMID- 30117954
TI  - Fast and wide-range optical beam steering with ultralow side lobes by applying an
      optimized multi-circular optical phased array.
AB  - A multi-circular optical phased array (OPA) is proposed and investigated through
      simulation to realize fast and wide-range optical beam steering with ultralow
      side lobes. The proposed multi-circular OPA has a circularly symmetrical
      distribution, and its radical element spacings are optimized by a modified
      genetic algorithm to achieve the best side lobe suppression. Specifically, the
      peak side lobe level (PSLL) of the far-field pattern in 0 degrees  beam direction
      reaches as low as 0.0715 for a 73-element optimized multi-circular OPA, which is
      much better than a multi-circular OPA with uniform radical element spacing (the
      PSLL is 0.3686). The prominent feature of the proposed OPA is that, once the OPA
      is optimized towards a specific elevation direction by the modified genetic
      algorithm, a wide-angle optical beam steering with nearly the same side lobe
      suppression can be achieved without updating the OPA distribution, which makes it
      possible for fast optical beam steering over a wide scanning range. In the
      simulation, ultralow side lobe beam steering with an elevation angle from 0
      degrees  to 30 degrees  and an azimuth angle from 0 degrees  to 360 degrees  is
      achieved with the PSLL variation less than 0.001. The relationship between the
      optimized PSLL and the elevation angle used for OPA optimization is also
      investigated, which is helpful in achieving the best side lobe suppression for
      different scanning ranges. The proposed OPA is expected to find applications such
      as laser radar, high-resolution display, and free space optical communications.

PMID- 30117955
TI  - Elemental composition analysis of granite rocks using LIBS and LA-TOF-MS.
AB  - Qualitative and quantitative analysis of the raw granite rocks acquired from
      deposits in the Hunza district, Gilgit area of Pakistan were studied using laser
      induced breakdown spectroscopy (LIBS) and laser ablation time-of-flight mass
      spectrometry (LA-TOF-MS). The optical emission spectra of the granite rocks used
      in artificial jewelry and for flooring tiles show the emission lines of (Si, Ca,
      K, Fe, Mg, Al, Na, and Li) and (Si, Ca, K, Fe, Mg, Al, Ti, Na, Ba, and Li),
      respectively. The mass spectra of these granite rocks were also studied with the
      LA-TOF-MS, revealing analogous elemental compositions. The results obtained using
      LIBS and LA-TOF-MS for the raw granite samples display their ability as powerful
      and complementary tools for the compositional analysis of the geological samples.

PMID- 30117956
TI  - Calibration method for division of focal plane polarimeters.
AB  - The division of focal plane polarimeters is fabricated out of nanowire
      polarization filters attached to the surface of a focal plane array. Due to
      limitations in the manufacturing process, the transmissivity of each nanowire
      polarization filter is different, resulting in a combination of inhomogeneities
      in transmittance and detector response, and which also yields the problem of
      polarization imaging uniformity, a more complicated method than traditional
      intensity imaging. This study presents a brand new nonuniformity correction
      method for solving the correction inaccuracies in the traditional method. The
      method corrected the polarization filter transmittance with detector gain based
      on a new method for calculating the degree of linear polarization (DoLP). This
      paper includes the theoretical derivation, experimental testing, and numerical
      simulation. In this simulation environment, the DoLP value was accurately
      calculated.

PMID- 30117957
TI  - Diffracted radiance not proven to be fundamental quantity in nonparaxial scalar
      diffraction theory: comment.

PMID- 30117958
TI  - Continuously tunable true-time delay lines based on a one-dimensional grating
      waveguide for beam steering in phased array antennas.
AB  - In this paper, we propose integrated one-dimensional (1D) grating waveguide-based
      true-time delay (TTD) lines on a silicon-on-insulator (SOI) platform. Through
      optimizing the structure of the proposed waveguide, a time delay of 77.23 ps/mm
      can be readily achieved in a wavelength tuning range from 1540.20 nm to 1558.97
      nm. Compared to conventional photonic crystal waveguide-based TTDs, the proposed
      waveguide occupies 70% less chip surface and has much lower propagation loss when
      compared with 2D photonic crystal devices. Therefore, a larger time delay can be
      achieved on-chip. To facilitate low loss coupling from strip waveguides to 1D
      grating waveguides and vice versa, a novel step taper is designed and shows a
      coupling efficiency of over 78%. Based on the 1D grating waveguide, a 1*4 beam
      steering module is designed and simulated. A wide beam steering angle from -67.84
      degrees  to 67.84 degrees  for the X-band four-element phased array antenna with
      an array pitch size of 1.25 cm is obtained.

PMID- 30117959
TI  - Ultra-high-speed indirect x-ray imaging system with versatile spatiotemporal
      sampling capabilities.
AB  - A new generation of cameras has made ultra-high-speed x-ray imaging at
      synchrotron light sources a reality, revealing never-before-seen details of sub
      surface transient phenomena. We introduce a versatile indirect imaging system
      capable of capturing-for the first time-hundreds of sequential x-ray pulses in 16
      bunch mode at the European Synchrotron Radiation Facility, recording at 5.68 Mfps
      over dozens of microseconds, with an effective exposure of 100 ps. The versatile
      multiplex camera construction of the system allows for various arrangements,
      including different scintillator configurations, and simultaneous imaging with
      different resolutions and regions of interest. Image results from a gas gun
      impact experiment, in which an additive manufactured aluminum lattice was
      dynamically compressed, is presented as a demonstration of the system's
      capabilities.

PMID- 30117960
TI  - Second-order interferometric autocorrelation for measuring group velocity
      dispersion and pulse broadening of femtosecond pulses.
AB  - Femtosecond pulse broadening and group velocity dispersion (GVD) were measured
      using a second-order interferometric autocorrelation technique. Two reference
      laser pulses of 36 fs and 55 fs were generated first in a Ti:sapphire oscillator
      and then passed through the optical elements of Ti:sapphire crystal and BK7 and
      fused silica glasses. For rectangular Ti:sapphire crystal and BK7 and fused
      silica slabs, material dispersion, and for fused silica prisms, material as well
      as angular dispersions were systematically measured. The experimental results
      were then compared with theoretical models, showing excellent agreement. The
      result of this work shows that one can rely very well on theoretical expressions
      to calculate the GVD of materials mentioned in this work and femtosecond pulse
      broadening.

PMID- 30117961
TI  - Compressed sensing hyperspectral imaging in the 0.9-2.5  MUm shortwave infrared
      wavelength range using a digital micromirror device and InGaAs linear array
      detector.
AB  - A hyperspectral imaging system based on compressed sensing has been developed to
      image in the 0.9-2.5 MUm shortwave infrared wavelengths. With a programmable
      digital micromirror device utilized as spatial light modulator, we have
      successfully performed spectrally resolved image reconstruction with a 256
      element InGaAs linear array detector without traditional raster scanning or a
      push-broom mechanism by a compressed sensing (CS) single-pixel camera approach.
      The chemical sensitivity of the imaging sensor to near-infrared (NIR) overtone
      signatures of hydrocarbons was demonstrated using hydrocarbon and ink patterns on
      glass, showing spectral selectivity for the chemical components. Compared to
      point-by-point raster scanning, we show that the CS scheme can effectively
      accelerate image acquisition with lower but reasonable quality.

PMID- 30117962
TI  - Forward fiber Fourier transform spectrometer modeling and design with PZT phase
      modulation real-time compensation.
AB  - Piezoelectric ceramic transducers (PZTs) are often applied in all-fiber Fourier
      transform spectrometers (FFTSs) to realize phase modulation. Combining a PZT and
      optical fiber features, a theoretical FFTS modeling is established. We
      systematically deduced the main causes of spectral errors and the factors of the
      instrumental resolution, then designed a new FFTS system and provided real-time
      compensation methods for spectral errors. We creatively employed two Mach-Zehnder
      interferometers by winding the sensing arms of the two on the same PZT cylinder
      to realize the dual optical path experiencing the same and simultaneous phase
      modulation. A processing circuit is designed to achieve selective sampling of the
      test interferogram, avoiding the spectral artifacts generated by the PZT phase
      discontinuities. The narrow line width of the reference spectrum is obtained at
      the same time for real-time calibration of spectral shift resulting from
      dispersion and other phase errors. By the comparison of the original
      interferogram and spectrum with those after compensation, the experiments
      validated that the system design could effectively compensate for the spectral
      errors caused by PZT and optical fiber physical limitations. Finally, the
      improved ideas are discussed if the FFTS prototype is to be applied to test a
      real-time gas spectrum.

PMID- 30117963
TI  - All-optical wavelength conversion for telecommunication mode-division
      multiplexing signals in integrated silicon waveguides.
AB  - An all-optical wavelength conversion method for telecommunication-band mode
      division multiplexing (MDM) signals is proposed in integrated silicon waveguides
      by using the four-wave mixing effect with a dual-mode pump. By engineering the
      dispersion profile of the integrated silicon waveguide, the phase-matching
      conditions are realized simultaneously for the TE01 mode and the TE11 mode of the
      MDM signal in the telecommunication band, and they can be converted to the idler
      modes simultaneously. In a 1.2-cm-long waveguide, the 3-dB conversion bandwidth
      reaches 58 nm with a conversion efficiency of -22.3  dB pumped by a 100-mW TE01
      and 105-mW TE11 pump source.

PMID- 30117964
TI  - Cylinder-type fiber-optic Vernier probe based on cascaded Fabry-Perot
      interferometers with a controlled FSR ratio.
AB  - We designed a cylinder-type fiber-optic Vernier probe based on cascaded Fabry
      Perot interferometers (FPIs) in this paper. It is fabricated by inserting a short
      single-mode fiber (SMF) column into a large-aperture hollow-core fiber (LA-HCF)
      with an internal diameter of 150 um, which structures a length adjusted air
      microcavity with the lead-in SMF inserted into the LA-HCF from the other end. The
      length of the SMF column is 537.9 um. By adjusting the distance between the SMF
      column and the lead-in SMF, the spectral change is displayed intuitively, and the
      Vernier spectra are recorded and analyzed. In sensitivity analysis, the probe is
      encapsulated in the medical needle by ultraviolet glue as a small body
      thermometer when the length of the air microcavity is 715.5 um. The experiment
      shows that the sensitivity of the Vernier envelope is 12.55 times higher than
      that of the high-frequency comb. This design can effectively reduce the
      preparation difficulty of the optical fiber Vernier sensor based on cascaded
      FPIs, and can expand the applied fields by using different fibers and materials.

PMID- 30117965
TI  - Optimization of a multiblaze grating in reflection using a free-form profile.
AB  - Diffraction gratings are very important in hyperspectral imaging. Their desired
      diffraction efficiency is dictated by the sensitivity of the detector in the
      spectral band of interest and the luminance of the scene to be observed. If the
      desired diffraction efficiency curve is established in this spectral band of
      interest, the remaining work is to design a diffraction grating that meets this
      demand. This paper is concerned with blazed gratings in reflection, and the
      geometry of the grating will therefore depend on this reference curve, the
      spectral band, and the optimization order. The simplest form is a grating with a
      uniform profile that is optimized at a single-blaze wavelength. It is a monoblaze
      grating. When such grating cannot meet the requirements in terms of diffraction
      efficiency, a multiblaze grating optimized at several blaze wavelengths is
      required. The objective of this paper is to propose a method of optimization of
      this multiblaze grating, i.e., how to find the number of blaze wavelengths
      necessary as well as their value to answer the requirements in term of
      diffraction efficiency.

PMID- 30117966
TI  - Temperature field investigation of hydrogen/air and syngas/air axisymmetric
      laminar flames using Mach-Zehnder interferometry.
AB  - In this study, the optical method of Mach-Zehnder interferometry (MZI) is
      utilized in order to explore the flame structure and temperature field of
      syngas/air and hydrogen/air flames. Two axisymmetric burners with inner diameters
      of 4 mm and 6 mm are used for temperature field measurement of hydrogen and
      syngas, respectively. The effects of fuel composition, equivalence ratio, and
      Reynolds number (Re) are investigated at ambient condition (P=0.87 bar, T=300 
      K). Three different H2/CO fuel compositions with hydrogen fractions of 30%, 50%,
      and 100% are studied. Temperature profiles are reported at four different
      sections above the burner tip. Measured temperatures using the interferometry
      method are compared with thermocouple data and good agreement between them is
      observed. The results obtained in this investigation indicated that the MZI can
      be applied for accurate determination of flame front and temperature field,
      especially for high-temperature flames where other methods cannot be properly
      utilized. Analyses of the data reduction method revealed that the exact
      determination of the refractive index distribution and reference temperature is
      critical for accurate determination of the temperature field. The results
      indicated that by increasing the Re, the maximum flame temperature is enhanced.
      Increasing the equivalence ratio leads to expansion of the flame radial
      distribution (at the same distance from the burner tip). At higher distances from
      the burner tip, temperature increases uniformly from the flame boundary toward
      the flame axis, while at lower heights it shows reduction at the burner axis. By
      increasing the CO content of fuel, the maximum flame temperature increases at all
      equivalence ratios except at the stoichiometric condition, where SH100
      illustrates the highest maximum flame temperature.

PMID- 30117967
TI  - 870  fs, 448  kHz pulses from an all-polarization-maintaining Yb-doped fiber
      laser with a nonlinear amplifying loop mirror.
AB  - We demonstrate a mode-locked long all-polarization-maintaining fiber laser with a
      nonlinear amplifying loop mirror. The fiber oscillator directly delivers 221 ps
      chirped pulses at the repetition rate of 448 kHz. The pulses can be further
      amplified up to 134 nJ and compressed down to 870 fs by a grating pair. This kind
      of laser is self-starting and stable long term, and it has potential application
      in high-power fiber amplification for industrial applications.

PMID- 30117968
TI  - Liquid crystal lens with corrected wavefront asymmetry.
AB  - We propose a simple technique allowing the correction of the inherent wavefront
      asymmetry in electrically variable liquid crystal lenses with relatively small
      diameters. This is achieved by splitting the peripheral hole patterned electrode
      of the lens in the direction of the ground-state anisotropy axis. Optical
      aberrations are measured before and after the split. It is demonstrated that a
      significant correction is achieved with a trade-off of trefoil increase in the
      direction of the split. This increase is then eliminated by the further
      segmentation of the peripheral electrode.

PMID- 30117969
TI  - Grating-assisted-cylindrical-resonant-cavities interlayer coupler.
AB  - A grating-assisted-cylindrical-resonant-cavities (GARC) interlayer coupler made
      of Si/SiO2 is designed and simulated to achieve efficient and broadband
      interlayer coupling. This coupler consists of three cylindrical resonant
      cavities: two waveguide cavities in the horizontal direction and one cylindrical
      via cavity in the vertical direction. The resonant strengths of the two
      cylindrical waveguide cavities are enhanced by circular Bessel-function-defined
      gratings and distributed Bragg reflectors. The interlayer coupling efficiency of
      this Si/SiO2 GARC coupler is simulated as etac=68%(-1.7 dB) for transverse
      electric polarization at 1.55 MUm wavelength, which is generally higher than
      those of conventional rectangular silicon-on-insulator gratings with additional
      features such as reflectors, overlayers, chirped periods, dual gratings, etc. The
      GARC couplers are predicted to have favorable attributes compared to previous
      couplers, including wider operational bandwidth (deltalambda,1 dB=270  nm),
      larger tolerance to inplane misalignment (+/-2  MUm for 1 dB extra loss), easier
      grating patterning (wider grating ridges), smaller footprint (20 MUm in
      diameter), and more flexible choices of interlayer distances (2-5 MUm). A
      sensitivity analysis is also provided as a guide in fabrication. In general, it
      is found that the vertical dimensions of the GARC couplers need to be carefully
      controlled while the horizontal dimensions are less critical.

PMID- 30117970
TI  - Electrically tunable transmission-type beam deflector using liquid crystal with
      high angular resolution.
AB  - Highly efficient transmission-type beam deflectors that have high angular
      resolution have been widely used for various applications. Continuously tunable
      beam deflectors have also been needed for many purposes. An indium-tin-oxide
      (ITO), widely used for transparent electrodes, was placed on the upper and lower
      glass substrate. The ITO layer on the lower substrate was patterned by the
      contact mask aligner for relatively wide input and output pad compared to main
      grating ITO patterns in the active area. These input and output pads on the lower
      substrate are connected to each driving integrated circuit (IC), which has 360
      channels for continuous control. A small pixel pitch of grating patterns of 6 MUm
      (the electrode width is 3 MUm with a 3 MUm spacing) was developed, and the
      maximum diffraction angle is calculated and measured at 2.541 degrees  with a
      wavelength of 532 nm. A minimal cell gap of 2.5 MUm was applied for the full 2pi
      phase modulation by using a high-birefringence liquid crystal. A driving module
      for continuous beam steering is also developed and applied to the beam deflector
      system. A diffraction efficiency of about 50.9% is observed at an angle of
      diffraction about 2.541 degrees .

PMID- 30117971
TI  - Demonstration of 40  GBaud intradyne transmission through worst-case atmospheric
      turbulence conditions for geostationary satellite uplink.
AB  - An optical communications system employing intradyne reception and offline
      digital signal processing is tested over a 10.45 km link through the atmosphere.
      40 GBaud transmission using binary phase-shift keying in the C-band is
      demonstrated and compared with laboratory measurements. Simultaneous
      photodetector measurements show that the turbulence in the atmospheric channel is
      representative for relevant and worst-case conditions in the geostationary
      satellite uplink scenario.

PMID- 30117972
TI  - Dynamics simulation and experiment of smooth end face grinding on photonic
      crystal fiber.
AB  - A smooth end face is the critical factor for the application of photonic crystal
      fiber (PCF) to enhance coupling efficiency. A number of air holes distributed on
      the cladding make the surface a discontinuous structure. For the sake of
      acquiring a high-quality end surface of PCF, this paper proposes a detailed study
      first on dynamics simulation of the grinding process of PCF using a finite
      element model with a verification experiment later. To facilitate the
      calculation, the grinding is simplified as a single grain to cut the material on
      the location between two holes. The process of material removal is analyzed on
      the basis of force curve obtained by changing the cutting depth and position,
      respectively. Theoretical and experimental results illustrate that the earliest
      material collapse occurs on the rim of the air hole, and brittle cracks extend
      along circumferential and axial direction of the hole; the damage on the edge of
      the hole is more severe with the increment of grain tip radius and cutting depth.
      Keeping the grinding force stable can achieve the process in the ductile regime,
      and a smooth surface can be obtained by polishing with abrasive paper of fine
      grit.

PMID- 30117973
TI  - In-plane coupled Fabry-Perot micro-cavities based on Si-air Bragg mirrors: a
      theoretical and practical study.
AB  - In-plane Fabry-Perot cavities based on deeply etched Bragg mirrors are used in
      many microphotonic applications including sensing, telecom, and swept laser
      devices. A main limitation to their performance is the small free spectral range
      (FSR) and low finesse. The FSR limits the dynamic range or the wavelength tuning
      range, while the linewidth limits the resolution. In this work, we propose
      coupled Fabry-Perot micro-cavities that greatly enhance the FSR, besides reducing
      the linewidth, which lead to higher finesse and better performance. The proposed
      structure is modeled and etched on Si substrate to a depth of 150 MUm using the
      deep reactive ion etching technology. Optical measurements indicate an enhanced
      FSR of more than 140 nm and a quality factor of 3152 using coupled cavities as
      compared to only 9 nm FSR for a single cavity of the same length. The over
      etching and surface roughness, being the main effective fabrication tolerances,
      are modeled and extracted from the measurements.

PMID- 30117974
TI  - High-precision calibration method for shear ratio based on the shearing wavefront
      feature extraction of a phase plate.
AB  - A new method based on the shearing wavefront feature extraction (SWFE) of a phase
      plate is proposed to accurately estimate the shear ratio of the system. The
      relationship between the shear ratio of a quadriwave lateral shearing
      interferometer based on a randomly encoded hybrid grating (REHG) and the
      measurement sensitivity, dynamic range, and wavefront retrieval accuracy is
      analyzed to provide a theoretical guidance for practical application. The
      simulation result of the SWFE method shows that the relative error of the shear
      ratio value is about 1.8*10-3, within the acceptable range of the system. In the
      experiment, two fused quartz phase plates etched with step change edge grooves
      were introduced to calibrate the shear ratio of the REHG wavefront diagnosis
      system. Then, the etching depths of these two phase plates and the figure error
      of a spherical surface were characterized by the REHG. A comparison with a ZYGO
      GPI interferometer exhibits that the testing results by the REHG are highly
      precise, which further confirms the effectiveness of the SWFE method in the shear
      ratio calibration. This shear ratio calibration method is available for similar
      kind of shearing interferometric wavefront sensor.

PMID- 30117975
TI  - Precise and robust binocular camera calibration based on multiple constraints.
AB  - Precise calibration of a binocular vision system is the foundation of binocular
      vision measurement. In this paper, we propose a highly precise and robust
      binocular camera calibration method, which is devoted to minimize the error
      between the geometric relation of 3D reconstructed feature points and the ground
      truth, such as adjacent distance error, collinear error, and right-angle error.
      In addition, the reprojection error and epipolar are introduced to satisfy the
      homography relation and epipolar geometry theory better. We optimize all
      intrinsic parameters, extrinsic parameters, and distortion parameters to minimize
      the objective function, which is the sum of a series of nonlinear least squares
      terms. Levenberg-Marquardt iterative algorithm is used to find the optimal
      solution of the camera parameters. To test the precision and robustness of the
      proposed method, both actual measurement experiments and Gauss noise-adding
      experiments are carried out. The experimental results show that compared with the
      other two calibration methods in the contrast experiment, the distance
      measurement error, collinear error, and right-angle error are reduced
      dramatically. It is noticeable that in Gauss noise-adding experiments, the
      calibration parameters estimated by the proposed method are more stable.

PMID- 30117976
TI  - Numerical analysis of a multi-pass pumping Yb:YAG thick-disk laser with minimal
      heat generation.
AB  - A theoretical model is established to describe the dynamic behavior and
      fractional thermal load of a multi-pass pumping Yb:YAG thick-disk laser, which is
      pumped at 1030 nm and emits laser radiation at around 1048 nm. The fractional
      thermal load, the temperature of the thick-disk crystal, and the operational
      properties for different ambient temperatures and different output coupler
      transmissions are investigated in detail. The results show that the pump
      saturation effect and the laser threshold are sensitive to the ambient
      temperature and the output coupler transmission, which affect the fractional
      thermal load and the laser extraction efficiency. Furthermore, a new design
      scheme is proposed to realize "zero thermal load" throughout the output range by
      dynamically adjusting the output coupler transmission.

PMID- 30117977
TI  - Octave-spanning optical frequency comb based on a laser-diode pumped Kerr-lens
      mode-locked Yb:KYW laser for optical frequency measurement.
AB  - We developed an optical frequency comb based on a Yb:KYW laser. Soft-aperture
      Kerr-lens mode-locking at the cavity transverse-mode degeneration enabled us to
      generate 360 mW from a 750 mW pump laser diode. This resulted in spectral
      broadening over one octave using just a photonic crystal fiber. We achieved a
      free-running linewidth of 15 kHz in the carrier-envelope offset frequency by
      optimizing the cavity group delay dispersion, crystal position, and pump laser
      power, which led to a residual phase noise of 0.51 rad during phase-locking. We
      measured the frequency drift of a cavity-stabilized laser for a clock transition
      in Yb171+.

PMID- 30117978
TI  - Reusable thin-film all-polymer couplers for vertical light coupling to single
      mode waveguides.
AB  - A reusable all-polymer coupler using gratings and tapers for vertical light
      coupling to single-mode planar waveguides is demonstrated. Numerical simulations
      are performed to optimize the tapers and gratings to increase the coupling
      efficiency. A hot-embossing replication technique is used for the fabrication of
      waveguide sensors and gratings, which is adaptable to mass production, such as
      roll-to-roll processes. The external grating is reversibly bonded to the
      waveguide via van der Waals forces, and the thus realized re-usability reduces
      the fabrication costs. The utility of the structure is shown by using these
      grating couplers for testing of asymmetric Mach-Zehnder interferometers.

PMID- 30117979
TI  - Ultrashort pulse generation with an erbium-doped fiber laser ring cavity based on
      a copper oxide saturable absorber.
AB  - A soliton mode-locked erbium-doped fiber (EDF) laser has been experimentally
      demonstrated using copper oxide (CuO) thin film as a saturable absorber (SA). The
      dispersion of the EDF cavity including the CuO-SA was balanced by a suitable
      length of single-mode fiber (SMF). The fabricated CuO-SA has 3.5% modulation
      depth and 3.3  MW/cm2 saturation intensity. The mode-locked train pulses have 1.7
      ps pulse width and 983 kHz repetition rate, while the pulse energy and output
      power are 1.29 nJ and 1.27 mW, respectively, at maximum pump power of 159 mW.
      These results indicate that the CuO thin film is a good SA candidate for a fiber
      laser operating at a low pump power. To the best of our knowledge, this is the
      first demonstration of a CuO-SA-based mode-locked fiber laser.

PMID- 30117980
TI  - Interference reduction using pattern modulation and demodulation for light-coding
      depth cameras.
AB  - Depth extraction systems with multiple light-coding depth cameras (LCDCs) have
      been widely used in the field of three-dimensional reconstruction in recent
      years. However, interference among the depth cameras would significantly
      deteriorate the quality of depth images and thus limit their efficiency in
      various applications. In this paper, we first establish the linear illumination
      model of multiple LCDCs to study the property of interference. Since the
      interference-free pattern is hard to distinguish from the interfered pattern, we
      present an interference reduction scheme based on pattern modulation and
      demodulation to address this problem. Projected patterns from the LCDCs are then
      uniformly modulated using a coefficient matrix. Afterwards, we further put
      forward an interference-alignment-based solution to demodulate the captured image
      frames, thereby fast recovering the interference-free pattern of a single LCDC.
      Depth images can finally be generated based on the recovered interference-free
      pattern. Experimental results from simulated and real-world examples show that
      the proposed scheme can effectively reduce the impact of interference and improve
      the quality of depth images.

PMID- 30117981
TI  - Optical design of a distributed zoom concentric multiscale meteorological
      instrument.
AB  - A meteorological moderate resolution sensor requires large field of view (FOV)
      and low distortion imaging. At present, a fixed-focus camera combined with a
      whiskbroom scanning mechanism or a fixed-focus multi-camera combined with
      pushbroom scanning mechanism is being used. Owing to the fixed focal length of
      the camera, a large FOV causes the difference of imaging distance and ground
      imaging angle between the nadir point and the edge of the FOV to be significantly
      large, resulting in a large difference in the resolution between the nadir point
      and the edge of the FOV. The study proposes to simultaneously adopt a distributed
      zoom concentric multiscale system to realize a large FOV, low distortion, and
      high quality imaging to coordinate with different compensation lenses to achieve
      a different FOV corresponding to different focal lengths, where the resolution
      drop between the nadir point and the edge of the FOV is reduced. To ensure the
      same illumination of the entire FOV, the entire system possesses the same F# with
      different FOVs exhibiting different entrance pupil diameters. The study analyzes
      the principle of aberration compensation of a concentric multiscale system when
      both the FOV and entrance pupil diameter are changed and completes three groups
      of optical design of different focal lengths with uniform F#. The results
      indicate that the system has advantages of low distortion and high imaging
      quality in the entire FOV. Moreover, the resolution drop in the entire FOV is
      reduced to approximately 50% of the traditional design scheme. To verify the
      implementability of the system, a set of prototype manufacturing and imaging
      experiments are conducted to prove that the system has satisfactory
      implementability, and the imaging quality is also satisfactory.

PMID- 30117982
TI  - 1.6:1 bandwidth two-layer antireflection structure for silicon matched to the 190
      310  GHz atmospheric window.
AB  - Although high-resistivity, low-loss silicon is an excellent material for
      terahertz transmission optics, its high refractive index necessitates an
      antireflection treatment. We fabricated a wide-bandwidth, two-layer
      antireflection treatment by cutting subwavelength structures into the silicon
      surface using multi-depth deep reactive-ion etching (DRIE). A wafer with this
      treatment on both sides has <-20  dB (<1%) reflectance over 187-317 GHz at a 15
      degrees  angle of incidence in TE polarization. We also demonstrated that bonding
      wafers introduce no reflection features above the -20  dB level (also in TE at 15
      degrees ), reproducing previous work. Together these developments immediately
      enable construction of wide-bandwidth silicon vacuum windows and represent two
      important steps toward gradient-index silicon optics with integral broadband
      antireflection treatment.

PMID- 30117983
TI  - Study on the Shupe error of the elliptic fiber coil.
AB  - In this work, the fiber optic gyroscope (FOG) with an elliptic fiber coil (EFC)
      is applied to the inertial measurement of petroleum well trajectory for the
      special condition of the borehole diameter limitation in the inclinometer while
      drilling (IWD). The three-dimensional (3D) Shupe error mathematical model and
      finite element model of the EFC are established by the quadrupole symmetrical
      technique, which is based on the Shupe effect of fiber coil. Then, the simulation
      experiments and the temperature experiments of the EFC are carried out to verify
      the correctness of the mathematical model. Under this prerequisite, the influence
      of the structure parameters of the EFC on the Shupe error is analyzed. In order
      to compare the rotation rate error between the EFC and the circular fiber coil
      (CFC), the temperature experiments of the EFC and the CFC are carried out with
      the same temperature excitation when the fiber length, the layers of fiber coil,
      and the radius of fiber coil of the EFC are the same as those of the CFC. The
      results show that the bias stability of the EFC is 35% to 39% smaller than that
      of the CFC before the temperature compensation, and after the temperature
      compensation, the bias stability of the EFC is 49% to 70% smaller than that of
      the CFC.

PMID- 30117984
TI  - High-accuracy measurement of the focal length and distortion of optical systems
      based on interferometry.
AB  - A figure measuring interferometer (FMI) method is proposed for high-accuracy
      measurement of the focal length and distortion of optical systems simultaneously.
      FMI uses the Zernike coefficients of interference fringe to identify the image
      point position precisely, and then measures the distance between the image points
      under the different fields to determine the image height. The field of view can
      also be accurately obtained by a precise rotating platform. Linear fitting
      between the field of view and the image height is used to calculate the focal
      length and distortion. The experimental results indicate that FMI has a relative
      expanded standard uncertainty of less than 0.01% for focal length and 0.02% for
      distortion. In brief, the proposed method is feasible for measurement of the
      focal length and distortion with high accuracy, promising further industrial
      applications.

PMID- 30117985
TI  - High-power tunable low-noise coherent source at 1.06  MUm based on a surface
      emitting semiconductor laser.
AB  - Exploiting III-V semiconductor technologies, vertical external-cavity surface
      emitting laser (VECSEL) technology has been identified for years as a good
      candidate to develop lasers with high power, large coherence, and broad
      tunability. Combined with fiber amplification technology, tunable single
      frequency lasers can be flexibly boosted to a power level of several tens of
      watts. Here, we demonstrate a high-power, single-frequency, and broadly tunable
      laser based on VECSEL technology. This device emits in the near-infrared around
      1.06 um and exhibits high output power (>100  mW) with a low-divergence
      diffraction-limited TEM00 beam. It also features a narrow free-running linewidth
      of <400  kHz with high spectral purity (side mode suppression ratio >55  dB) and
      continuous broadband tunability greater than 250 GHz (<15  V piezo voltage, 6 kHz
      cutoff frequency) with a total tunable range up to 3 THz. In addition, a compact
      design without any movable intracavity elements offers a robust single-frequency
      regime. Through fiber amplification, a tunable single-frequency laser is achieved
      at an output power of 50 W covering the wavelength range from 1057 to 1066 nm.
      Excess intensity noise brought on by the amplification stage is in good agreement
      with a theoretical model. A low relative intensity noise value of -145  dBc/Hz is
      obtained at 1 MHz, and we reach the shot-noise limit above 200 MHz.

PMID- 30117986
TI  - Large-area flexible infrared nanowire grid polarizer fabricated using nanoimprint
      lithography.
AB  - We fabricated a 4-in large-area flexible infrared nanowire grid polarizer using a
      nanoimprint and metal thermal evaporation process. To protect the Si master
      template, as well as to prolong the service life of it, we first fabricated a
      nickel template as an alternative by an electroforming process. Then, the
      nanowire grid structure was transferred from this template to IPS substrate by a
      thermal nanoimprint process. Finally, Al was deposited on the IPS nanowire
      structure by vertical thermal evaporation technology. The results of the infrared
      optical test reveal that the TM transmittance of the polarizer is greater than
      60% in the 4-5.71 MUm and 5.73-6.7 MUm wavelength ranges, and, especially, it is
      greater than 70% in the wavelength ranges of 4.70-5.69 MUm and 5.75-6.59 MUm. The
      extinction ratio is more than 20 dB in the wavelength range of 3.6-6.7 MUm,
      proving that the polarizer has good polarization characteristics. The flexible
      infrared nanowire grid polarizer has potential applications in the fields of
      curved surface monitoring equipment and polarized imaging equipment.

PMID- 30117987
TI  - Beat noise reduction utilizing the transient acoustic-wave response of an optical
      fiber in Brillouin grating-based optical low coherence reflectometry.
AB  - We periodically generated a transient Brillouin grating by using continuous-wave
      pump light and 50 MHz pulse-wave pump light with optical low coherence
      reflectometry (OLCR). We extracted the Stokes light generated by the decaying
      part of the grating with an optical switch, and this enabled us to block the
      pulse-wave pump light from entering the balanced mixer, resulting in a reduction
      in the noise caused by the beat between the local oscillator light and the pump
      light. For the first time, to the best of our knowledge, we succeeded in
      detecting a Stokes light with an OLCR, despite the fact that the states of
      polarization of the probe and pump light waves were parallel, and this encouraged
      us to construct a polarization-independent OLCR for diagnosing optical modules
      and three-dimensional objects.

PMID- 30117988
TI  - Optical scanning of laser line sensors for 3D imaging.
AB  - In scanning laser triangulation sensors for 3D imaging, the achievable throughput
      is strongly limited by the moving mass. By realizing an optical scanning approach
      rather than repositioning the entire sensor, this limitation could be reduced,
      leading to a reduced measurement time. This work presents sensor system
      geometries in which only the optical path of a line triangulation sensor is
      manipulated by a tip-tilt mirror. In the proposed rotational scanning systems,
      either the illumination path or both the illumination and the reflection path are
      manipulated. By using ray-tracing simulation, the performance of the scanning
      systems are optimized and possible disadvantages can be determined up front.
      Using geometric relations, the surface profile can be reconstructed from the
      measured sensor data, the mirror position, and the model parameters. Experimental
      results show that the image quality of the proposed rotational scanning systems
      is comparable to systems based on classical translational scanning motion.

PMID- 30117990
TI  - Advanced Infrared Technology and Applications: introduction.
AB  - This special issue of Applied Optics on Advanced Infrared Technology and
      Applications collects significantly expanded refereed papers presented at the
      conference of the same name, held in Quebec City, Canada, Sept. 27 to Sept. 30,
      2017. All the authors who participated at the conference were contacted and
      invited to contribute to this special issue. Furthermore, the AO dedicated issue
      on AITA was open to contributions from other practitioners of IR, through direct
      contact and a call for papers published in AO.

PMID- 30117989
TI  - Theoretical investigation of the regenerative amplification of ultrashort pulses
      in a high-pressure transverse electric CO2 laser.
AB  - We have developed a theoretical model for the regenerative amplification of
      ultrashort mid-infrared radiation in high-pressure transverse electric discharge
      CO2 lasers. This model is based on counter-propagating wave equations that are
      combined with Boltzmann equation, six-temperature, and circuit-coupled kinetic
      models. For the first time to our knowledge, the effect of spontaneous emission
      is taken into account. The model describes noise behavior, contrast ratio, and
      self-lasing of amplified spontaneous emission. The proposed scheme allows the
      attainment of a few-picosecond pulse with GW-level peak power and contrast ratio
      on the order of 106 in the 9 MUm range.

PMID- 30117991
TI  - Unimorph deformable mirror with an integrated strain feedback layer.
AB  - The correction accuracy of a pint-sized unimorph deformable mirror (DM) is
      significantly influenced by the nonlinear hysteresis error of piezoelectric
      ceramics, especially in an open-loop state. Moreover, the control bandwidth is
      also reduced by the nonlinearity. In this paper, we fabricated a three-unit pint
      sized unimorph DM with strain gauges integrated on the actuators as a feedback
      layer for the first time. An experimental platform was built and utilized to test
      each electrode's strain signal. Testing results show that, under quasi-static
      condition, the hysteresis curve of the mirror's central displacement is corrected
      and the hysteresis rate could be reduced from 11% to less than 2% by adopting the
      strain feedback signal. More specifically, the DM's initial surface, Zernike
      defocus, together with spherical aberration can also be corrected by this method,
      and the correction accuracy is improved more than 20% compared to the open-loop
      state. By introducing a closed-loop control the gaps of the DMs under open loop
      are supplied. This demonstrates that adding a strain feedback layer is promising
      to enhance the performance of a unimorph DM.

PMID- 30117993
TI  - Stokes imaging spectropolarimeter based on channeled polarimetry with full
      resolution spectra and aliasing reduction.
AB  - A Stokes channeled interference imaging spectropolarimeter with full-resolution
      spectra and aliasing reduction is presented. The sensor uses a Wollaston prism, a
      Savart polariscope, and a linear analyzer as a birefringent interferometer, along
      with two high-order retarders to incorporate channeled polarimetry employing a
      tempo-spatially mixed modulated mode with no internal moving parts and offering a
      robust system. The performance of the system is verified through laboratory
      tests. Compared with the previous sensors, the most significant advantage of the
      described instrument is that the reconstructed spectra retain the resolution of
      the interferometer, and the errors in the reconstructed spectral resolved
      polarization state caused by aliasing between the interference channels are
      suppressed effectively. Additionally, the advantages of the interferometer are
      maintained, such as compact structure and high optical throughput.

PMID- 30117992
TI  - Impacts of a collection system on laser-induced breakdown spectroscopy signal
      detection.
AB  - Collecting strong enough and repeatable signals from laser-induced plasmas is the
      primary goal of laser-induced breakdown spectroscopy optical detection systems.
      Typically, the light emitted from the plasma is refracted by the lens, collected
      by the fiber, and measured by the spectrometer. In the present work, we
      established a three-dimensional model to systematically evaluate the overall
      emission collected from different positions of the plasma for a typical optical
      collection system composed of a focus lens and a collection fiber, and
      sensitivity analyses were further performed. In addition, experiments were
      conducted and partially validated the model. Results showed that for the
      collection system with an optical fiber located on the focal point of the
      collection lens, the collection efficiency distribution is almost constant within
      a large cylindrical-shaped area, while for that located off the focal point,
      there is a rhombus-shaped area with higher collection efficiency than other
      areas. This much higher collection efficiency area is small in size but has a
      large impact on the detected spectral intensity. The spatially distributed
      collection efficiency on the lens parameters, such as size and position, was
      further discussed to clarify the impacts of the collection system. Furthermore,
      sensitivity analyses were performed to evaluate the impact of the collection
      system on the signal repeatability. Based on these calculations, recommendations
      for the design of the collection for optimized spectral intensity and stability
      were proposed.

PMID- 30117994
TI  - Generation of optical Bessel beams with arbitrarily curved trajectories using a
      magnetic-liquid deformable mirror.
AB  - We propose a new strategy to curve the trajectory of the central lobe of a zero
      order Bessel beam and a first-order Bessel beam along their propagation axis. Our
      method involves modifying the phase of a beam that is incident on an adaptive
      mirror. As examples, we show that the most intense lobe of the beam can follow a
      parabolic trajectory, a cubic trajectory, or a trajectory made by a combination
      of these orders. By using a phase correction emulating the effect of cylindrical
      mirrors, the central lobe always preserves its symmetry. Theoretical simulations
      were reproduced in the laboratory using a magnetic-liquid deformable mirror. The
      parabolic trajectory of the 60-MUm central spot of a zero-order Bessel beam
      exhibits a 0.6-mm off-axis shift after 30-cm-length propagation.

PMID- 30117995
TI  - Three-dimensional characterization of debris clouds under hypervelocity impact
      with pulsed digital inline holography.
AB  - The increasing space debris poses a great threat to in-orbit spacecraft and
      satellites, because its hypervelocity impact can bring about fatal mechanical and
      electrical damage to them. This work applies pulsed digital inline holography
      (DIH) to measure three-dimensional (3D) positions and shapes of the debris clouds
      generated by the hypervelocity impact in the Whipple shield. Detailed operation
      procedures of synchronizing the pulse DIH system with the impact event and
      removing the strong plasma radiation are presented, ensuring the successful
      capture of the transient state of ultrafast ejecta. Experiments on a 2.25 mm
      aluminum sphere impacting a 0.5 mm thickness aluminum target plate with a
      velocity of 3.6 km/s are carried out at the Hypervelocity Impact Research Center
      of the China Aerodynamics Research and Development Center, and results show that
      the holographic fringes are clearly recorded and the debris fragments are
      reconstructed and located accurately, agreeing well with the results measured by
      laser shadowgraph. This work demonstrates the powerful capability and great
      potential of DIH in the diagnostics of hypervelocity impact.

PMID- 30117996
TI  - Highly coherent supercontinuum in the mid-infrared region with cascaded tellurite
      and chalcogenide fibers.
AB  - We numerically investigate two-step supercontinuum (SC) generation using cascaded
      tellurite and chalcogenide fibers with all-normal group velocity dispersion
      pumped by a femtosecond laser at 2 MUm. The optimized tellurite fiber is a hybrid
      microstructured optical fiber with a core surrounded by 12 rods. It has flat
      normal chromatic dispersion from 2 to 5 MUm. The chalcogenide fiber is a double
      core fiber with flat normal chromatic dispersion from 4 to 10 MUm. The output SC
      spectrum from the best candidate fibers spans from 0.78 to 8.3 MUm with coherence
      of unity all over the spectrum. Such high coherence pulse with broad spectrum
      will be valuable for many applications in tomography, ultrafast transient
      absorption spectroscopy, etc. The proposed fiber structures are all-solid and are
      feasible for fabrication with the common rod-in-tube method. This implies that
      two-step SC is a potential way to obtain broad, highly coherent SC in the mid
      infrared.

PMID- 30117997
TI  - Rectangular-structure-based pose estimation method for non-cooperative
      rendezvous.
AB  - Pose estimation for spacecraft is widely recognized as an important technology
      for space applications. Many space missions require accurate relative pose
      between the chaser and the target spacecraft. Stereovision is a usual mean to
      estimate the pose of non-cooperative targets during proximity operations. In this
      paper, an accurate algorithm for pose estimation is proposed by taking advantage
      of the geometric structure of the object. With stereo cameras, our approach
      employs the corners of the solar panel as features and uses bundle adjustment to
      improve the accuracy. Simulation results demonstrate that our method improves the
      precision and robustness for non-cooperative spacecraft pose estimation. Our
      laboratory experiments further validate the approach. The results show that the
      rotation angle error of our method is within 0.8 degrees , and the measurement
      error in translation is less than 0.4% at the distance from 3 m to 1.2 m.

PMID- 30117998
TI  - Improving the resolution of two-photon microscopy using pixel reassignment.
AB  - An imaging system combining parallel detection and two-photon excitation is
      presented in this paper. In the proposed method, seven avalanche photodiodes
      (APD) are used in the detection path. The light is guided onto the APD sensor by
      a fiber bundle with seven fibers. The circular arranged fiber end faces together
      function as a detection array. The outer contour fiber ends deviate from optical
      axis center and thus obtain higher frequency information. Seven images are
      acquired simultaneously by the detection array. By using deconvolution and pixel
      reassignment to process the images acquired, both the resolution and the contrast
      of the final image are enhanced. The capability of image quality enhancement of
      the system constructed is demonstrated successfully both by theoretical
      simulation and experimental results.

PMID- 30117999
TI  - Interferometric particle imaging of ice particles using a multi-view optical
      system.
AB  - Interferometric particle imaging enables particle size estimation in a wide range
      [from 10 MUm to a few millimeters] depending on the optical system design. With a
      multi-view optical system, it is possible to extract more information about the
      3D morphology of the particle. In this study, multi-view interferometric out-of
      focus imaging of ice particles is performed in a backward-scattering
      configuration. It is used to estimate ice particle volume and thus to reduce
      uncertainty concerning particle size estimation. It is further used to better
      analyze the presence of nearby particles whose images overlap.

PMID- 30118000
TI  - Windowed Fourier ridges for demodulation of carrier fringe patterns with
      nonlinearity: a theoretical analysis.
AB  - Accurately extracting phase or phase derivative is the most important requirement
      in optical metrology. However, in practice, there are many error sources, among
      which nonlinear distortion in fringe patterns is often encountered. Several
      techniques have been proposed over time to remove the nonlinearity error. Among
      these techniques, the windowed Fourier ridges (WFR) algorithm has been shown to
      be an effective solution insensitive to nonlinearity, but it lacks a theoretical
      justification. In this paper, we theoretically analyze the local frequency
      estimation error and phase extraction error, which not only proves the mentioned
      insensitivity, but also supports the performance prediction and error control,
      and thus is very important and useful in optical measurement. The theoretical
      results have been verified by computer simulations. Other error sources such as
      model error and noise are also compared and discussed.

PMID- 30118001
TI  - Integrated athermal arrayed-waveguide grating multiplexer and demultiplexer with
      all-metal compensating rod for broadband temperature application.
AB  - In this paper, a unique device that can act as both multiplexer and demultiplexer
      is proposed with two all-metal compensating rods that makes the compensated chip
      almost the same spectrum profile as the original one. In this way a flat-top
      athermal arrayed-waveguide grating module of 100-GHz*40-ch is successfully
      fabricated. A small center wavelength shift of +/-25  pm is achieved for the
      ultra-wide temperature range from -40 degrees C to 85 degrees C with the low
      insertion loss change of less than +/-0.14  dB.

PMID- 30118002
TI  - Bessel-like beam generated by an axicon based on parallel-plate waveguides.
AB  - The axicon is the simplest and most effective optical element for generating the
      zero-order Bessel-like beam. The zero-order Bessel-like beam, which has the
      characteristics of small spot size, high brightness, good direction, and large
      collimation distance, can be applied to optical micromanipulation and power
      transmission. In this paper, we proposed and designed a structure for phase
      manipulation based on parallel-plate waveguides that can be used to realize the
      functionality of the axicon in the terahertz (THz) region. Meanwhile, we
      characterized the influence of the cone angle of the axicon and the waist radius
      of the incident Gaussian beam on the generated zero-order Bessel-like beam by
      simulation. The planar structure, consisting of a parallel stack of thin copper
      plates, can be easily fabricated to fulfill the phase requirement to realize the
      zero-order Bessel-like beam and also can be utilized in THz imaging systems, THz
      sensing systems, THz communication systems, etc.

PMID- 30118003
TI  - Highly-sensitive carbon disulfide on-line detection system based on deep
      ultraviolet absorption spectroscopy, and its application in liquid-seal
      reliability assessment.
AB  - This paper investigated a potential instrument for carbon disulfide in situ
      measurement with high precision and strong anti-interference capability. A
      compact and automated carbon disulfide detection system was developed using a
      fiber opto-electronic sensing device. A custom software interface based on
      LabVIEW was developed. The multi-wavelength least-squares method based on
      differential optical absorption spectroscopy was employed for improved detection
      and the anti-interference capabilities of the system. The detection limit of the
      system (signal-to-noise ratio=3) was determined to be 1 ppb per meter. Using this
      scheme, the reliability of a liquid-seal was verified to have carbon disulfide
      leakage. Although the liquid level of the liquid-sealed carbon disulfide showed
      no significant change over 24 h, a residue concentration of over 30 ppm remained
      detectable on the surface.

PMID- 30118004
TI  - Continuum removal for ground-based LWIR hyperspectral infrared imagery applying
      non-negative matrix factorization.
AB  - Continuum removal is vital in hyperspectral image analysis. It enables data to be
      used for any application and usually requires approximations or assumptions to be
      made. One of these approximations is related to the calculation of the spectra of
      the background's blackbody temperature. Here, we present a new method to
      calculate the continuum removal process. The proposed method eliminates the
      calculation for ground-based hyperspectral infrared imagery by applying two
      acquisition sets before and after using the heating source. The approach involves
      a laboratory experiment on a long-wave infrared (LWIR; 7.7-11.8 MUm), with a LWIR
      macro lens, an Infragold plate, and a heating source. To calculate the continuum
      removal process, the approach applies non-negative matrix factorization (NMF) to
      extract Rank-1 NMF, estimate the downwelling radiance, and compare it with that
      of other conventional methods. NMF uses gradient-descent-based rules (GD) and non
      negative least-squares (NNLS) optimization algorithms to obtain Rank-1 NMF. A
      comparative analysis is performed with 1%-20% additive noise for all algorithms
      by using the spectral angle mapper and normalized cross correlation (NCC).
      Results reveal the promising performance of NMF-GD (average of 72.5% similarity
      percentage using NCC) and NMF-NNLS (average of 77.6% similarity percentage using
      NCC).

PMID- 30118005
TI  - Determination of the thermal boundary conductance of gold nanoparticles in
      aqueous solution using a method based on nanobubble generation.
AB  - We present a method to determine the thermal boundary conductance of gold
      nanoparticles in aqueous solution. The novel approach consists of two steps:
      first, measuring photoacoustic signals originated by laser-induced nanobubbles at
      different energies and, second, fitting the experimental data with a nanobubble
      generation model developed in a previous work. We used this method on gold
      nanoparticles with diameters from 10 to 70 nm. Within this range, we obtained
      values of the thermal boundary conductance between 180  W/m2 K and 225  W/m2 K.

PMID- 30118006
TI  - Improved light collection in OA-ICOS cells using non-axially-symmetric optics.
AB  - We show that the introduction of a non-axially-symmetric optical component can
      significantly improve light collection in instruments that use off-axis
      integrated cavity output spectroscopy (OA-ICOS). OA-ICOS is a robust technique
      for field measurements of scarce trace gases, but the inherent skewness of its
      output makes light collection onto small detectors difficult. Here, we derive the
      constraining effect of skewness in OA-ICOS cavities with Herriott alignments, and
      show how this constraint can be overcome by the addition of a non-axially
      symmetric optical component. We describe such a component consisting of eight
      ZnSe wedges designed for the OA-ICOS-based Chicago Water Isotope Spectrometer,
      and show that this component increases the instrument's signal-to-noise ratio by
      a factor of three. The ratio of improvement is expected to be even larger in
      compact OA-ICOS instruments.

PMID- 30118007
TI  - Phase-noise model for actively linearized frequency-modulated continuous-wave
      ladar.
AB  - Understanding the effects of laser phase noise on frequency-modulated continuous
      wave distance measurements is important in evaluating ranging accuracy. The
      standard white-frequency-noise assumption is commonly used to predict the ranging
      performance. However, other noise sources are typically present that can further
      degrade the heterodyne beat signal and make this assumption invalid. In addition,
      many ranging systems employ active sweep linearization techniques that can impact
      the phase noise. Here, we present a phase-noise model for assessing the accuracy
      of a phase-locked swept laser source.

PMID- 30118008
TI  - Polarization-insensitive broadband terahertz metamaterial absorber based on
      hybrid structures.
AB  - A polarization-insensitive broadband terahertz (THz) metamaterial absorber is
      presented in this paper. The metamaterial absorber consists of several circular
      and rhombus metallic patches as a unit cell and a metallic ground plane separated
      by a polyimide dielectric layer. By increasing the number of circular and rhombus
      patches with different sizes, the operating bandwidth of the absorber is
      broadened because of the resonances of each single patch getting close enough and
      merging together in the frequency range. The simulated results show that the
      absorption bandwidth covers a broadband frequency range of 0.22-0.33 THz with the
      highest absorptivity of 99.93% at 0.3035 THz. The full width at half maximum is
      as wide as 0.155 THz, and the bandwidth of over 80% absorptivity is 0.1315 THz.
      This study promises applications in THz detection and communication systems, and
      the operation bandwidth is very convenient and compatible for electronic THz
      sources.

PMID- 30118009
TI  - Modeling for detecting weld defects based on magneto-optical imaging.
AB  - A magneto-optical (MO) imaging nondestructive testing (NDT) method for
      ferromagnetic weldments has been proposed. The mechanism of MO imaging was
      analyzed by the Faraday MO effect, magnetic domain theory, and magnetic
      hysteresis loops. Then, the relation between MO images and their corresponding
      excitation voltages was investigated. To explain the MO imaging system, magnetic
      domain distribution models of various welding states were established. These
      models are excited by two kinds of magnetic fields. One is the external magnetic
      field (Hex), and the other is a weldment remanence field (Mr) after Hex is
      removed. Relations of magnetic field excitation voltages, thickness of the spacer
      plate, and the corresponding MO images were also researched, which indicates the
      proposed NDT method can be used to detect incomplete penetration defect. Then, an
      experiment that uses MO imaging to detect the defects of high-strength steel
      (HSS) weldment was performed. Experimental results proved this method can detect
      crack, sag, and incomplete penetration of weldment effectively. Finally, a series
      of welded joint MO images of the HSS weldment were captured, which are used as
      the input data of the defect classification model established by using principal
      component analysis and an error backpropagation neural network, and the accuracy
      of this classification model can achieve 92.8%.

PMID- 30118010
TI  - Simulated annealing optimization in wavefront shaping controlled transmission.
AB  - In this research, we present results of simulated annealing (SA), a heuristic
      optimization algorithm, for focusing light through a turbid medium. Performance
      of the algorithm on phase and amplitude modulations has been evaluated. A number
      of tips to tune the optimization parameters are provided. The effect of
      measurement noise on the performance of the SA algorithm is explored.
      Additionally, SA performance is compared with continuous sequential and briefly
      with other optimization algorithms.

PMID- 30118011
TI  - Study on skylight polarization patterns over the ocean for polarized light
      navigation application.
AB  - Polarized skylight navigation has excellent navigation performance with no error
      accumulation over time and low susceptibility to interference. The skylight
      polarization distribution contains rich directional information, such as the
      solar meridian, the neutral point, and the polarization angle, which plays a key
      role in the polarization navigation. But up to now the polarizations of both
      sunlit and moonlit skies have been investigated mainly over the land. In this
      work, the polarization distribution patterns of the skylight over the East China
      Sea and the Yellow Sea were studied. The polarization patterns were captured
      continuously during daytime and nighttime by using a full-sky imaging polarimetry
      system and then compared with the simulation results using the libRadtran
      radiative transfer software package. The result shows that the skylight
      polarization distribution over the sea has almost the same pattern as that on the
      land. The accuracy of the angle of polarization and the degree of polarization
      dropped significantly under the cloudy sky. It was found that when the ship
      sailed on the sea, the direction of the real meridian was close to the solar
      azimuth during the daytime and close to the lunar azimuth during the nighttime.
      It was also found that the nautical twilight polarization distribution was
      affected by both the solar polarization and the lunar polarization, but the solar
      polarization was dominant. The experiments show that the skylight polarization
      distribution pattern over the sea can still be applied in the field of
      polarization navigation. Thus, it is feasible for ships and unmanned aerial
      vehicles to use the polarized skylight to navigate and orient on the sea.

PMID- 30118012
TI  - Integrated research of a multi-wavelength method in anisotropic scattering flame
      on soot temperature and radiative coefficient reconstruction.
AB  - At present, the studies of scattering flame problems combined with multi
      wavelength reconstruction technology are rather limited. In this paper, a multi
      wavelength method combined with a collocation spectral method (CSM)-discrete
      ordinates method (DOM) forward method is developed for the simultaneous
      reconstruction of temperature and inhomogeneous radiative coefficient of an
      axisymmetric laminar ethylene diffusion flame. The scattering source term in the
      radiative transfer equation is solved by the forward solution method based on
      DOM, which couples a spatial scheme of CSM and the spherical rings arithmetic
      progression quadrature. The Tikhonov regularized method is employed to overcome
      the ill-posed matrix to obtain the global radiative source term. The boundary
      radiation intensity is input into the algorithm as a known value for inversion of
      temperature, absorption coefficient, and scattering coefficient. The retrieval
      results demonstrate that the temperature and the radiation parameters of the
      scattering flame can be well reconstructed for the flame with axisymmetric
      distribution, even for the flame with noisy data. In addition, the scattering
      coefficient is more difficult to rebuild than temperature. The inversion accuracy
      does not deteriorate with a slight increase in noise. Also, the addition of
      scattering terms to the proposed algorithm can improve the accuracy in
      reconstructing the radiation parameters. The developed method in this paper would
      be useful for multispectral algorithms, which could be used in later experiments
      based on hyperspectral techniques.

PMID- 30118013
TI  - Directional second-harmonic generation controlled by sub-wavelength facets of an
      organic mesowire.
AB  - Directional harmonic generation is an important property characterizing the
      ability of nonlinear optical antennas to diffuse the signal in a well-defined
      region of space. Herein, we show how sub-wavelength facets of an organic
      molecular mesowire crystal can be utilized to systematically vary the
      directionality of second-harmonic generation (SHG) in the forward-scattering
      geometry. We demonstrate this capability on crystalline diamonoanthraquinone
      (DAAQ) mesowires with sub-wavelength facets. We observed that the radial angles
      of the SHG emission can be tuned over a range of 130 deg. This angular variation
      arises due to spatially distributed nonlinear dipoles in the focal volume of the
      excitation as well as the geometrical cross section and facet orientation of the
      mesowire. Numerical simulations of the near-field excitation profile corroborate
      the role of the mesowire geometry in localizing the electric field. In addition
      to directional SHG from the mesowire, we experimentally observe optical
      waveguiding of the nonlinear two-photon excited fluorescence (TPEF).
      Interestingly, we observed that for a given pump excitation, the TPEF signal is
      isotropic and delocalized, whereas the SHG emission is directional and localized
      at the location of excitation. All the observed effects have direct implications
      not only in active nonlinear optical antennas but also in nonlinear signal
      processing.

PMID- 30118014
TI  - High-power visibly emitting Pr3+:YLF laser end pumped by single-emitter or fiber
      coupled GaN blue laser diodes.
AB  - We demonstrate the high-power continuous-wave operation of a Pr3+:YLF laser end
      pumped by blue laser diodes. As the pump source, we used four 5 W single-emitter
      blue laser diodes and a >20  W fiber-coupled module. In single-emitter-diode
      pumping, we obtained pump-limited output powers of 6.7 and 3.7 W at 640 and 607
      nm, respectively. We successfully suppressed thermal aberration and obtained an
      output power of 3.4 W at a slope efficiency of 25% at 640 nm with good beam
      quality in the fiber-coupled module pumping.

PMID- 30118015
TI  - Dynamic Mach-Zehnder interferometer based on the lateral displacement of a point
      source array.
AB  - A dynamic Mach-Zehnder interferometer based on lateral displacement of a point
      source array is proposed. The point source array is generated by a point source
      and a phase grating, where four point sources are of identical intensity. The
      lateral displacement of each point source can be adjusted to introduce pi/2 phase
      steps in the interferograms. With a specially designed lens array in the spatial
      split imaging system, four separated and clear imaging interferograms can be
      captured in a single shot. Using a four-bucket algorithm, the phase distribution
      can be retrieved exactly, thereby realizing dynamic measurement. The experimental
      results show the feasibility and high precision of this dynamic Mach-Zehnder
      interferometer.

PMID- 30118016
TI  - Development and application of a low-cost smartphone-based turbidimeter using
      scattered light.
AB  - We demonstrate the development and application of a low-cost smartphone
      turbidimeter system to be used on water samples collected from natural resources.
      The proposed system depends on the spectroscopic measurements of both forward-
      and side-scattered light. A custom-designed cradle was fabricated using 3D
      printing, and plastic optical fibers were used to couple light from the
      smartphone's built-in flash and transmit the collected scattered light to the
      camera sensor. The performance parameters of the smartphone turbidimeter were
      investigated and compared to commercial systems, and the lowest limit of
      detection was found to be 5.58 NTU for forward-scattered detection. The results
      obtained in the proposed scattered-light-based spectroscopic turbidimeter and the
      practicality achieved by this extremely low-cost device will have a great impact
      on water science and technology.

PMID- 30118017
TI  - Scaling ultrashort laser pulse induced glass modifications for cleaving
      applications.
AB  - Ultrashort laser pulses allow for in-volume processing of glass through non
      linear absorption. This results in permanent material changes, largely
      independent of the processed glass, and it is of particular relevance for
      cleaving applications. In this paper, a laser with a wavelength of 1030 nm, pulse
      duration of 19 ps, repetition rate of 10 kHz, and burst regime consisting of
      either four or eight pulses, with an intra-burst pulse separation of 12.5 ns, is
      used. Subsequently, a Gaussian-Bessel focal line is generated in a fused silica
      substrate with the aid of an axicon configuration. We show how the structure of
      the modifications, including the length of material disruptions and affected
      zones, can be directly influenced by a reasonable choice of focus geometry, pulse
      energy, and burst regime. We achieve single-shot modifications with 2 MUm in
      diameter and 7.6 mm in length, exceeding an aspect ratio of 1:3800. Furthermore,
      a maximum length of 10.8 mm could be achieved with a single shot.

PMID- 30118018
TI  - Multistage single clad 2  MUm TDFA with a shared L-band pump source.
AB  - We report the experimental performance and simulation of a multiwatt two-stage
      TDFA using an L-band (1567 nm) shared pump source. We focus on the behavior of
      the amplifier for the parameters of output power Pout, gain G, noise figure NF,
      signal wavelength lambdas, and dynamic range. We measure the spectral performance
      of the TDFA for three specific wavelengths (lambdas=1909, 1952, and 2004 nm)
      chosen to cover the low-, mid-, and upper-wavelength operating regions of the
      wideband amplifier. We also compare the performance of the two-stage shared pump
      TDFA with a representative one-stage shared pump amplifier. A comparison of
      experimental results with simulation is presented.

PMID- 30118019
TI  - Fourier transform infrared spectrometer based on an electrothermal MEMS mirror.
AB  - This paper presents a micro Fourier transform infrared spectrometer (MUFTIR),
      enabled by an H-shaped electrothermal microelectromechanical systems (MEMS)
      mirror. A special driving method was developed for obtaining a linear, uniform
      speed motion of 186 MUm, and the tilting angle of the MEMS mirror was as small as
      0.06 degrees , so there was no need of complex closed-loop control. A telecentric
      lens was employed in the interferometer of the MUFTIR to reduce the influence of
      the MEMS mirror tilting effect. Also, a new phase interpolation algorithm,
      instead of the traditional fringe interval method, was applied in the process of
      the spectral reconstruction to improve the spectral stability. Finally, the new
      MUFTIR was applied in the composition prediction of soybeans, and the
      experimental results show that it can accurately measure grain moisture, protein,
      and fat contents.

PMID- 30118020
TI  - Time-resolved measurements of a swirl flame at 4  kHz via computed tomography of
      chemiluminescence.
AB  - Computed tomography of a chemiluminescence (CTC) system was implemented to
      provide time-resolved 3D measurements of an unconfined turbulent swirl flame.
      This system was designed in a cost-effective manner and employed three customized
      view registration assemblies to simultaneously capture eight projections of the
      target flame at a repetition rate of 4 kHz. Both time-resolved and time-averaged
      tomographic reconstructions were performed based on data acquired for a duration
      of 250 ms. Both qualitative and quantitative validations suggested the
      correctness of our implementation. The time-resolved instantaneous
      reconstructions successfully captured the evolution of the structural features of
      the swirl flame such as local extinctions and the helical mode. Based on the
      reconstructions, the centroids of chemiluminescence for all the layers were
      calculated. The trajectory of these centroids provided insights into the flow
      motion and suggested a rotating helical structure of the swirl flame. These
      results demonstrated the feasibility of resolving the dynamics of turbulent swirl
      flames with a kHz temporal resolution using the relatively inexpensive CTC
      system.

PMID- 30118021
TI  - Visualizing spatial distribution of atmospheric nitrogen dioxide by means of
      hyperspectral imaging.
AB  - We have developed a method to monitor the slant column density of nitrogen
      dioxide in the lower troposphere using a compact hyperspectral camera with a high
      spectral resolution of 1 nm at the full width half-maximum. Measurements of
      skylight spectra were conducted in wavelength regions of 460-490 nm and 550-610
      nm to retrieve the slant column densities of nitrogen dioxide, in addition to
      water vapor and oxygen dimer. The results of ground-based measurements are shown
      for the cases of urban air pollution and aircraft emission near an airport
      runway.

PMID- 30118022
TI  - High-power continuous-wave supercontinuum generation in highly nonlinear fibers
      pumped with high-order cascaded Raman fiber amplifiers.
AB  - A novel method for efficient generation of a high-power, equalized continuous
      wave supercontinuum source in an all-conventional silica fiber architecture is
      demonstrated. Highly nonlinear fiber is pumped in its anomalous dispersion region
      using a novel, high-power, L-band laser. The L-band laser encompasses a sixth
      order cascaded Raman amplifier which is pumped with a high-power Ytterbium-doped
      fiber laser and amplifies a low-power, tunable L-band seed source. The
      supercontinuum generated 35 W of power with ~40% efficiency. The supercontinuum
      spectrum was measured to have a high degree of flatness of better than 5 dB over
      400 nm of bandwidth (1.3-1.7 MUm, limited by spectrum analyzer range) and a power
      spectral density in this region of >50  mW/nm. The extent of the SC spectrum is
      estimated to be up to 2 MUm.

PMID- 30118023
TI  - Spectrum reconstruction in Fourier transform imaging spectroscopy based on high
      performance parallel computing.
AB  - In this paper, parallel-processing algorithms for spectrum reconstruction in
      Fourier transform imaging spectroscopy are proposed using high-performance
      parallel computing. Because of the huge amount of interference data, traditional
      algorithms are inefficient and time-consuming. It is necessary to process
      interference data as soon as possible to form spectral data for research and
      economy. We take advantage of parallel computing based on the graphics processing
      unit (GPU) to enable higher efficiency and reduced operation time. Furthermore,
      traditional algorithms for processing interferograms on the central processing
      unit are introduced for comparison. The experimental results show that the
      runtime is reduced from 1.144 to 0.332 ms using our parallel algorithms, and for
      the huge amount of data, the designed parallel-processing mechanism on the GPU
      has advantages over the traditional pipeline.

PMID- 30118024
TI  - Transverse mode instability threshold enhancement in Yb-doped fiber lasers by
      cavity modification.
AB  - To enhance the transverse mode instability (TMI) threshold of a fiber oscillator,
      a novel configuration is presented. In this configuration the oscillator cavity
      length is considerably reduced and the remaining active fiber is released out of
      the cavity to absorb the rest of the pump power and amplify the output signal of
      the cavity. In fiber oscillators, the index gratings generated by both forward
      and backward propagating signals can interact with light propagating in the
      backward and forward directions and degrade the output beam quality. In the
      proposed modified configuration, due to lower intra-cavity forward and backward
      signal power the index grating is smoothed and the TMI threshold is increased.
      Experimental results indicate that this modified configuration has a higher TMI
      threshold than a conventional fiber oscillator. Finally a higher TMI threshold is
      achieved in the bidirectional pumping scheme of the modified configuration.

PMID- 30118025
TI  - Optical design of dental light using a remote phosphor light-emitting diode
      package for improving illumination uniformity.
AB  - The projection-type dental lighting based on the remote phosphor light-emitting
      diode (LED) package is designed to enhance uniformity of illuminance and
      correlated color temperature (CCT) on a target plane and to remove glare in the
      eyes of the patient. This dental lighting enables dentists to illuminate
      effectively the patient's mouth by increasing the inner area (50  mm*25  mm)
      described in ISO 9680. The optical module comprised of the LED package and
      optical lens is modeled to satisfy the inner area wider than 100  mm*50  mm and
      illuminance over 5,000 lx per the designed optical module. The fabricated
      prototype dental lighting contains four optical modules, and the maximum
      illuminance is 22,786 lx. The measured inner area is 105  mm*74  mm, and the
      ratio of inner area to outer area is about 76%. Also, the CCT variation is below
      450 K in total illuminance pattern.

PMID- 30118026
TI  - Spatially resolved temperature measurement in the carbon dioxide arc under
      different gas pressures.
AB  - Carbon dioxide (CO2) is a promising alternative to sulfur hexafluoride for high
      voltage circuit breaker applications. It is important to have a detailed
      understanding of CO2 arc properties. In this paper, radial temperature
      distribution of the free burning direct current arc in pure CO2 was investigated.
      Optical emission spectrometry was applied under different pressures (0.5 atm, 1
      atm, and 1.5 atm) and at different axial positions (1 mm, 2 mm, 3 mm above the
      cathode). Assuming local thermodynamic equilibrium, the Fowler-Milne method was
      adopted for O I 715.67 nm and O I 777.19 nm in the periphery of the arc, and the
      single-line method was adopted for C II 657.81 nm near the center of the arc.
      Radial temperature profiles obtained by these two methods were combined at the
      position where normal temperature was assigned. The results indicate that near
      the center of the arc, higher pressure would lead to lower temperature; as the
      distance from the cathode to the position measured increases, the maximum
      temperature in the arc center would decrease. In addition, the temperature would
      decrease more sharply toward the periphery if the central temperature of the arc
      is higher.

PMID- 30118027
TI  - Hybrid attack on an optical cryptosystem based on phase-truncated Fourier
      transforms and a random amplitude mask.
AB  - In this paper, the security of a cryptosystem based on phase-truncated Fourier
      transforms (PTFTs) and a random amplitude mask (RAM) is evaluated. In the
      cryptosystem, fake keys used as encryption keys in the second PTFT-based
      structure are generated by the first PTFT-based structure in which the RAM is
      encoded by random phase masks (RPMs) used as public keys. Compared to the
      classical PTFT-based encryption scheme, the security level of the cryptosystem is
      improved by using cascaded PTFTs to encode the encryption keys and the plaintext
      simultaneously. However, it is found that a known plaintext-ciphertext pair can
      provide enough constraints in the iterative process to retrieve the fake keys,
      which then can be used to retrieve unknown arbitrary plaintext from the
      corresponding ciphertext. Based on the analysis, we propose a specific attack
      based on hybrid iterative processes to break the cryptosystem. Two iterative
      processes with different constraints are involved in the proposed attack. The
      first known-plaintext-attack (KPA)-based iterative process is used to retrieve
      two fake keys with the help of two public keys and a known plaintext-ciphertext
      pair, while the second amplitude-phase retrieval algorithm-based iterative
      process with a median filter is employed to retrieve the plaintext from the
      corresponding ciphertext using two retrieval fake keys. To the best of our
      knowledge, it is the first time that the cryptosystem is attacked by the KPA
      based iterative algorithm successfully. Numerical simulation results validate the
      feasibility and effectiveness of the proposed attack.

PMID- 30118028
TI  - Modeling of an active terahertz imaging system in brownout conditions.
AB  - We present a theoretical evaluation of a subterahertz (subTHz) system to image
      through a scattering medium composed of scatterers of sizes close to the
      wavelength. We specifically study the case of sand grain clouds created by
      helicopter rotor airflow during landing in arid areas. The different powers
      received by one pixel of a matrix made of subTHz sensors are identified.
      Photometric and antenna-based sensors are considered. Besides the thermal
      contribution to the noise, we focus our attention on the radiation backscattered
      by the brownout. It appears that a configuration where the source and the camera
      are distant is the most promising configuration and is realistic for embedded
      systems.

PMID- 30118029
TI  - Subwavelength-spaced transmissive metallic slits for 360-degree phase control by
      using transparent conducting oxides.
AB  - We propose an apparatus that allows for active control of the transmission phase
      up to 360 degrees  through subwavelength-spaced metallic slits partially filled
      with indium tin oxide (ITO). Incident light is coupled to the guided mode in the
      metallic slit at one side. After going through the slit with a certain length,
      light is coupled out to free space at the other side. The transmission phase is
      governed by the mode index and the slit length. By applying bias to the ITO in
      the metallic slit, it is possible to control the mode index, which in turn leads
      to tuning of the transmission phase. The judiciously designed slit configuration
      facilitates the individual control of the relative phase between the neighboring
      slit with a subwavelength distance. This phenomenon is different from resonance
      based metasurface approaches that suffer from limited range of the phase change.
      It is believed that the devised configuration may open novel promising future
      applications such as hologram imaging with phase spatial light modulators, light
      field infrared microscopy, and beam forming and steering devices.

PMID- 30118030
TI  - Accurate determination of dielectric permittivity of polymers from 75  GHz to 1.6
      THz using both S-parameters and transmission spectroscopy: publisher's note.
AB  - This publisher's note corrects a reference in Appl. Opt.56, 3287 (2017)APOPAI0003
      693510.1364/AO.56.003287.

PMID- 30118031
TI  - Optimized laser-induced breakdown spectroscopy for the determination of high
      toxic lead in edible colors.
AB  - An optimized laser-induced breakdown spectroscopy (LIBS) system was utilized as a
      robust tool for the detection of high toxic lead (Pb) in often used edible colors
      available in local markets. Edible colors are extensively used in different food
      stuffs and sweet dish items. To attain a highly sensitive LIBS system for the
      determination of trace amounts of toxic Pb in edible colors and to achieve the
      best detection limit, various parametric dependence studies were performed. The
      quantitative determinations were accomplished under the condition of local
      thermodynamic equilibrium in terms of optically thin plasma. Besides toxic Pb,
      other elements like Ca, Mg, Fe, and Na were also detected in edible colors. To
      estimate the concentration of toxic lead in edible colors, calibration curves
      were plotted by preparing standard samples of different lead concentrations in an
      edible colors matrix. Results of the LIBS technique were compared with the
      outcomes of the same samples studied using a standard analytical technique of
      inductively coupled plasma-optical emission spectroscopy to confirm the
      contemporary LIBS setup. The color samples were found above the safe permissible
      level due to the mass of toxic lead. Limit of detection of the LIBS setup was
      found at 0.86+/-0.03  ppm for toxic lead present in edible color samples.

PMID- 30118032
TI  - Extending the depth of focus of fiber-optic optical coherence tomography using a
      chromatic dual-focus design.
AB  - We report a dual-focus fiber-optic probe designed to extend depth of focus (DOF)
      in high-resolution endoscopic optical coherence tomography. We exploited the
      broad spectral bandwidth of a supercontinuum source and, in the fiber probe, the
      foci of the 750-1000 nm and 1100-1450 nm inputs were axially chromatically
      shifted. The interference signals from the two spectral bands were measured with
      a Si camera-based spectrometer and an InGaAs camera-based spectrometer,
      respectively. We verified the feasibility of the design using a phantom composed
      of microparticles and swine small intestine tissue ex vivo. The results showed
      that a transverse resolution below 5 MUm over 300 MUm could be maintained, and
      that the extended DOF was 2 times larger than that of the single focus probe via
      the use of dual spectral band inputs and a chromatic focal shift.

PMID- 30118033
TI  - Effect of mechanical error on dual-wedge laser scanning system and error
      correction.
AB  - Compared with the traditional mechanical beam deflector in a beam-scanning
      system, the dual-wedge scanning system has several advantages, for example,
      compact structure, fast scanning speed, and low power consumption. High accuracy
      is the most important factor in dual-wedge scanning, but mechanical errors caused
      by machining or assembly errors adversely affect this scanning accuracy.
      Horizontal and angular mechanical errors appear between the incident light and
      the dual-wedge central optical axes. By building a mathematical model of an ideal
      dual-wedge scanning trajectory and a trajectory affected by mechanical errors,
      this paper analyzes the types and degree of influence on the scanning process, as
      well as the sensitivity of scanned images to different errors. Results show that
      the angular error has the most significant influence on the scanning image
      accuracy, in terms of trajectory shape and coverage. To correct the angular
      error, the two degrees-of-freedom flexible fine-tuning mechanism is customized
      based on the principle of the cantilever beam type. After finite element analysis
      and experimental validations, the fine-tuning mechanism can guarantee that the
      angular error in the dual-wedge central optical axes will be lower than 0.05 deg,
      thus ensuring scanning trajectory accuracy.

PMID- 30118034
TI  - Full electro-optic terahertz time-domain spectrometer for polarimetric studies.
AB  - We present a terahertz (THz) time-domain spectrometer dedicated to polarimetric
      studies. THz pulses are generated through optical rectification in a ?111?-cut
      cubic crystal. The ?111? crystal cut produces a THz polarization state similar to
      that of the exciting laser beam. Detection of the THz pulses is performed by
      electro-optic sampling in a similar crystal, and a dual detection scheme allows
      us to measure simultaneously the two polarization components of the THz beam. We
      experimentally illustrate that the polarization of the THz beam can be adjusted
      by adjusting the laser polarization. This technique alleviates the need for a
      polarization controller at THz frequencies.

PMID- 30118035
TI  - Calibration of a high spectral resolution lidar using a Michelson interferometer,
      with data examples from ORACLES.
AB  - The NASA Langley airborne second-generation High Spectral Resolution Lidar (HSRL
      2) uses a density-tuned field-widened Michelson interferometer to implement the
      HSRL technique at 355 nm. The Michelson interferometer optically separates the
      received backscattered light between two channels, one of which is dominated by
      molecular backscattering, while the other contains most of the light
      backscattered by particles. This interferometer achieves high and stable contrast
      ratio, defined as the ratio of particulate backscatter signal received by the two
      channels. We show that a high and stable contrast ratio is critical for precise
      and accurate backscatter and extinction retrievals. Here, we present retrieval
      equations that take into account the incomplete separation of particulate and
      molecular backscatter in the measurement channels. We also show how the accuracy
      of the contrast ratio assessment propagates to error in the optical properties.
      For both backscattering and extinction, larger errors are produced by
      underestimates of the contrast ratio (compared to overestimates), more extreme
      aerosol loading, and-most critically-smaller true contrast ratios. We show
      example results from HSRL-2 aboard the NASA ER-2 aircraft from the 2016 ORACLES
      field campaign in the southeast Atlantic, off the coast of Africa, during the
      biomass burning season. We include a case study where smoke aerosol in two
      adjacent altitude layers showed opposite differences in extinction- and
      backscatter-related Angstrom exponents and a reversal of the lidar ratio spectral
      dependence, signatures which are shown to be consistent with a relatively modest
      difference in smoke particle size.

PMID- 30118036
TI  - Integrated design of pi/2 converter and its experimental performance.
AB  - Transverse modes of light have been widely exploited in both classical and
      quantum optics in recent years. Among the devices to manipulate the transverse
      modes of light, a pi/2 converter is a fundamental and important one that analogs
      to the quarter-wave plate in the polarization degree of freedom. While a pi/2
      converter is typically achieved by a pair of well-adjusted cylindrical lenses, it
      suffers from complexity in its installation and adjustment, which strongly limits
      its practical applications. In this paper an integrated design of a pi/2
      converter is reported. We compute the necessary parameters for manufacturing
      according to refractive theory of a cylindrical surface. Based on the change of
      refractive indices, we simulate the response of Gouy phase versus wavelengths. We
      also implement an experiment to verify the conversion between Laguerre-Gaussian
      modes and Hermite-Gaussian modes by using our compact pi/2 converter to confirm
      its simple adjustment and reliable performance in practice.

PMID- 30118037
TI  - Comparative evaluation of signal-to-noise ratio and resolution of underwater
      imaging systems with artificial illumination.
AB  - Characteristics of different underwater imaging systems are compared based on the
      results of Monte Carlo simulations of light transport in the sea water. The
      consideration includes systems with continuous-wave illumination, modulated
      illumination, pulsed systems with time gating detection, and hybrid systems with
      probing pulse modulated at high frequency. To generalize the study, the ratio of
      SNRs of different systems when imaging a sinusoidal test pattern is analyzed.
      Pulsed systems are demonstrated to provide higher SNR as compared to continuous
      wave systems for typical imaging distances varying in the range 35-60 m, while
      systems with modulated illumination provide a SNR comparable to that for
      continuous-wave systems. Hybrid systems provide SNRs comparable to that in pulsed
      systems benefiting, however, from higher contrast transfer coefficient.

PMID- 30118038
TI  - Determination of optimized removal functions for imprinting continuous phase
      plates using fuzzy theory.
AB  - A new evaluation method based on fuzzy theory was proposed to assess the
      manufacturing efficiency and accuracy of continuous phase plates (CPPs) with
      magnetorheological finishing imprinting. Two-dimensional sinusoidal waves were
      employed to verify the effectiveness of the proposed method theoretically and
      experimentally in terms of two parameters, error root mean square and processing
      time, which indicate the accuracy and efficiency of CPP manufacture. The weight
      factor was used for balancing the priorities of processing time and accuracy in
      our method. The simulations and experiments were compared based on our proposed
      method. The results show that the optimum removal functions for various spatial
      periods result in good agreement between simulations and experiments, and
      furthermore, relative errors are 6.07%, 2.62%, and 6.00% for CPPs with spatial
      periods of 12 mm, 18 mm, and 30 mm, respectively. All the results indicate that
      the method provides a valid and feasible way to select an optimized removal
      function for imprinting the patterns of CPPs.

PMID- 30118039
TI  - Noise reduction in computational ghost imaging by interpolated monitoring.
AB  - An interpolation computational ghost imaging (ICGI) method is proposed and
      demonstrated that is able to reduce the noise interference from a fluctuating
      source and background. The noise is estimated through periodic illuminations by a
      specific assay pattern during sampling, which is then used to correct the bucket
      detector signal. To validate this method simulations and experiments were
      conducted. Light source intensity and background lighting were randomly varied to
      modulate the noise. The results show that good quality images can be obtained,
      while with conventional computational ghost imaging (CGI) the reconstructed
      object is barely recognizable. The ICGI method offers a general approach
      applicable to all CGI techniques, which can attenuate the interference from
      source fluctuations, background light noise, dynamic scattering, and so on.

PMID- 30118040
TI  - Precision measurements of optically thick alkali metal number density within a
      hybrid alkali metal cell.
AB  - The number density of alkali metal vapors and their ratio within hybrid cells is
      of great significance for the optimal rotation sensitivity of alkali metal-noble
      gas comagnetometers. To measure the number density of optically thick Rb vapor
      accurately within a hybrid cell containing optically thin K vapor and optically
      thick Rb vapor, a novel method combining alkali metal absorption spectroscopy and
      Raoult's law is proposed in this paper. The relative error between experimental
      results and results calculated by empirical formula is within +/-5% from 365 to
      450 K, and the measurement accuracy is improved more than 10 times compared to
      previous study. This novel method could be applied to check the number density
      ratio of alkali metal within hybrid cells more precisely.

PMID- 30118041
TI  - Experimental study of the morphological evolution of the millisecond-nanosecond
      combined-pulse laser ablation of aluminum alloy.
AB  - A comparative study of the interactions of the millisecond-nanosecond combined
      pulse laser and millisecond pulse laser with aluminum alloy is presented. During
      the interaction between the laser and aluminum alloy, the coupling effect of the
      nanosecond pulse laser on the molten pool formed by the millisecond laser is
      analyzed. During the nanosecond laser irradiation in the combined approach, the
      expansion velocity of the plasma plume reaches 600 m/s, while the laser ablation
      depth increased by approximately 9 times. Based on experiments, the high-speed
      shadow imaging method, correlation of the temperature evolution characteristics,
      and ablation morphology are considered for a comprehensive analysis. The coupling
      effect between the millisecond-nanosecond combined-pulse laser and aluminum-alloy
      molten pool phase is explained.

PMID- 30118042
TI  - Optical constants and electrochromic characteristics of MxWO3 bronzes.
AB  - Concentration (x) dependent ellipsometric data on three tungsten bronzes (HxWO3,
      LixWO3, NaxWO3) are investigated to examine the optical constants (n, k) and
      their electrochromic characteristics. Maximum decrease in the refractive index
      (n) and maximum increase in the extinction coefficient (k) are found as the
      limits of electrochromic effects. Differences in the optical constants of these
      three tungsten bronzes are perhaps due to different impurity scattering
      mechanisms associated with their individual unit cell configurations. Optical
      densities, coloration efficiencies, and the complex dielectric loss functions (
      1/epsilon) of tungsten bronzes have been calculated as the electrochromic
      parameters to be used in the electrochromic display systems. Oscillator
      strengths, dipole strengths, and the degrees of delocalization of the polaronic
      wave functions are calculated and found to be very low, giving the convincing
      argument that there is no indication of Drude free electron behavior in these
      bronzes, at least in the investigated concentration range.

PMID- 30118043
TI  - Optical tweezers for trapping in a microfluidic environment.
AB  - Optical tweezers use the force from a light beam to implement a precise gripping
      tool. Based purely on an optical principle, it works without any bodily contact
      with the object. In this paper we describe an optical tweezers that targets an
      application within the framework of nuclear magnetic resonance (NMR) spectroscopy
      of small objects, which are embedded inside a microfluidic channel that will be
      integrated in a micro-NMR detector. In the project's final stages, the whole
      system will be installed within the wide bore of a superconducting magnet. The
      aim is to precisely maintain the position of the object to be measured, without
      the use of susceptibility disturbing materials or geometries. In this
      contribution we focus on the design and construction of the tweezers. For the
      optical force simulation of the system we used a geometrical optics approach,
      which we combined with a ray fan description of the output beam of an optical
      system. By embedding both techniques within an iterative design process, we were
      able to design efficient optical tweezers that met the numerous constraints.
      Based on details of the constraints and requirements given by the application,
      different system concepts were derived and studied. Next, a highly adapted and
      efficient optical trapping system was designed and manufactured. After the
      components were characterized using vertical scanning interferometry, the system
      was assembled to achieve a monolithic optical component. The proper function of
      the optical tweezers was successfully tested by optical trapping of fused silica
      particles.

PMID- 30118044
TI  - Short-range azimuth measurement method based on the adaptive filtering mechanism
      using laser and magnetism.
AB  - In order to accurately measure the target position in the short range, this paper
      presents a measurement method based on the laser and magnetism composite (L-M)
      mechanism. A single-beam pulsed laser is used to measure the target distance
      dynamically. The magnetic sensor is used to acquire the scanning period signal,
      and the azimuth information is calculated by the L-M signal. A variable step-size
      least mean square algorithm with a step memory effect is designed to reduce the
      interference. The numerical simulation and experimental results show that the
      method of azimuth measurement has a good measurement accuracy and anti
      interference. In addition, this short-range azimuth measurement has a great
      potential in small moving bodies.

PMID- 30118045
TI  - Numerical optimization strategy for multi-lens imaging systems containing
      freeform surfaces.
AB  - With progress in freeform technology, freeform components are entering real
      system designs. Although freeform surfaces increase the degrees of freedom of
      systems, optimization strategies for placing multiple freeforms are still
      underdeveloped. We therefore investigated strategies for placing freeforms to
      achieve significant improvement in system performance for optical imaging
      systems. For demonstrating our findings and supporting our observations, we have
      chosen a Scheimpflug system and a lithography system. Several aspects are
      investigated and implemented in optimization strategies. These strategies are
      used to optimize and demonstrate the performance on selected examples, i.e.,
      multi-lens imaging systems containing one or two freeforms. Finally, we describe
      a workflow to guide the design process from start to the end for implementing
      freeforms in order to achieve improved system performance.

PMID- 30118046
TI  - Implementation of nearly arbitrary spatially varying polarization
      transformations: an in-principle lossless approach using spatial light
      modulators.
AB  - A fast and automated scheme for general polarization transformations holds great
      value in adaptive optics, quantum information, and virtually all applications
      involving light-matter and light-light interactions. We present an experiment
      that uses a liquid crystal on silicon spatial light modulator to perform
      polarization transformations on a light field. We experimentally demonstrate the
      point-by-point conversion of uniformly polarized light fields across the
      wavefront to realize arbitrary, spatially varying polarization states.
      Additionally, we demonstrate that a light field with an arbitrary spatially
      varying polarization can be transformed to a spatially invariant (i.e., uniform)
      polarization.

PMID- 30118047
TI  - Life cycle analysis of electrically actuated SMA spring using Talbot
      interferometry.
AB  - Electrically actuated shape memory alloys (SMAs) find widespread applications in
      engineering and science. Such materials are known to retain/remember their state.
      In the stressed/deformed state, when activated by the application of a suitable
      excitation mechanism, such as the use of heat or potential, they return to their
      original unstressed state. To test their reliability, it is a standard procedure
      to undertake a life cycle analysis. In this paper, the life cycle analysis of a
      SMA spring using the Talbot interferometric technique is reported. The life cycle
      of the SMA spring is analyzed in terms of the displacement drift, which sets in
      because of the functional fatigue generated due to its repeated use. Collimated
      light from a He-Ne laser transmitted through a beam splitter is converged through
      a focusing lens onto a plane mirror attached to the spring. Backreflected light
      from the mirror is incident on a set of two Ronchi gratings separated by the
      Talbot distance, forming a moire pattern. The resulting interferograms are
      analyzed using a fringe rotation mechanism. The angle of orientation is a
      function of displacement drift. There is deterioration in the SMA property
      because of repeated cycles, and the spring loses its ability to return to its
      original unstretched position. The values of the displacement drift generated
      after 1, 1000, 2000, 3000, 4000, and 5000 such cycles as measured using a Talbot
      interferometer are 0, 0.875, 1.275, 1.459, 1.720, and 1.859 mm, respectively. It
      is observed that the SMA effect deteriorates as the number of
      stretching/contraction cycles increases. The uncertainty analysis is also
      reported. The expanded uncertainty was determined to be 201.61 MUm.

PMID- 30118048
TI  - Influence of transversely inhomogeneous pseudo-thermal light source on lensless
      ghost imaging.
AB  - The influence of a transversely inhomogeneous pseudo-thermal light source on
      lensless ghost imaging is investigated theoretically and experimentally. Based on
      classical optical theory, a model of lensless ghost imaging with an inside
      inclined light source is analyzed. We use the optical path difference between
      different transverse positions of the light beam to estimate the degree of
      inhomogeneity. The results indicate that the transversely inhomogeneous light
      source decreases the visibility and signal-to-noise ratio of the reconstructed
      image. Finally, we implement experiments to verify our results using inclined
      ground glass.

PMID- 30118049
TI  - Short fiber resonant optic gyroscope using the high-frequency Pound-Drever-Hall
      technique.
AB  - Optical gyros are attractive angular rotation sensors based on the Sagnac effect.
      The phase modulation technique is adopted to detect the weak resonant frequency
      shift induced by the Sagnac effect, which determines the detection sensitivity of
      the gyros. The Pound-Drever-Hall (PDH) modulation is a mature laser frequency
      stabilization technique that is widely recognized. A resonant optic gyro equipped
      with a short and high-finesse fiber ring resonator employing the high-frequency
      PDH modulation technique is proposed and demonstrated. The modulation index and
      frequency are optimized to maximize the slope of the demodulation curve. Compared
      with the low-frequency modulation, the high-frequency PDH modulation increases
      the slope of the demodulation curve by a factor of 1.23 and achieves an extra
      15.8 dB of laser frequency noise suppression. The bias stability of the gyro
      output is improved from 9.6 degrees /h to 8 degrees /h, and the equivalent lock
      in frequency accuracy increases 12 dB.

PMID- 30118050
TI  - Study on baseline correction methods for the Fourier transform infrared spectra
      with different signal-to-noise ratios.
AB  - Removing the baseline from the spectra, which are measured by a Fourier transform
      infrared spectrometer (FTIR), is an important preprocessing step for further
      spectra analysis such as quantitative and qualitative analysis. An automatic
      baseline correction method named iterative averaging, which is based on the basic
      knowledge of moving average, is presented. We also compared it to other methods,
      such as rubber band, adaptive iterative reweight penalized least squares,
      automatic iterative moving average, and morphological weighted penalized least
      squares, using simulated and experimental spectra with different signal-to-noise
      ratios (SNRs) to evaluate the performance of these methods by performance metrics
      and to select an appropriate method to analyze FTIR spectra. Performance metrics
      such as root-mean-square error, goodness-of-fit coefficient, and chi-square are
      calculated. The iterative averaging method achieves the best results, which are
      judged by performance metrics values, when it is applied to the FTIR spectra with
      different SNRs. It also can correct the baseline of the FTIR spectra
      automatically, and improve the capability and adaptability of the unsupervised
      online analysis of the FTIR system effectively.

PMID- 30118051
TI  - Optoelectronic application of graphene nanoribbon for mid-infrared bandpass
      filtering.
AB  - In this study, an ultra-compact optoelectronic bandpass filter is proposed. A
      single piece of graphene nanoribbon (GNR) is placed between two input-output GNRs
      to form a Fabry-Perot-like cavity. The GNR, as a mid-infrared surface waveguide,
      enhances the compatibility with complementary metal oxide-semiconductor
      processing technologies. The transmission characteristics of the bandpass filter
      are tuned by the modulation of surface charge carrier density simply through
      changing the bias voltage applied on the GNR cavity, and thus a tunable filter at
      room temperature is achieved. It is found that increasing the gate voltage and
      the silica substrate thickness or middle GNR width alters the max peak of
      transmission spectra of the filter toward smaller wavelengths. In contrast,
      increasing the middle GNR length redshifts max peak of the filter toward longer
      wavelengths. The finite different time domain (FDTD) inhouse code has been
      employed to verify the designs.

PMID- 30118052
TI  - Sensitivity study on the effect of the optical and physical properties of coated
      spherical particles on linear polarization in clear to semi-turbid waters.
AB  - The influence of internal inhomogeneities within hydrosol particles on the
      polarization characteristics of light is investigated by combining an accurate
      coated sphere (core-shell) single-scattering model with a radiative transfer
      model that employs Stokes formalism and considers refraction of direct solar
      radiation at the air-water interface followed by single scattering. A Junge
      particle size distribution is assumed. Variations in what we call the "linear
      polarization phase function" (the degree of linear polarization as a function of
      scattering angle and the E-vector orientation as a function of scattering angle)
      are examined as a function of variations in the characteristics of the hydrosol
      particles. An extensive sensitivity study on the influence of variations in the
      real and imaginary parts of the refractive index of both the core and shell of
      the hydrosol particles and on the influences of variations in the ratio between
      the core radius and shell radius is conducted, varying the values of these
      parameters over the entire parameter space documented in the literature for
      actual hydrosol particles. In addition, calculations are conducted for specific
      parameter combinations in order to demonstrate the influence of some of the most
      important groups of hydrosols, namely, phytoplankton, gas bubbles, carbonaceous
      hydrosols, and mineral hydrosols, on the polarization field under water.
      Variations as a function of solar zenith angle are also investigated. Due to the
      assumption of single scattering, the results presented are relevant to conditions
      of low wind speed and a low scattering optical depth and/or low single-scattering
      albedo within the water body (clear to semi-turbid waters at shallow geometric
      depths and/or moderate to strong absorption within the water body) outside of
      Snell's window. Possible implications for aquatic animal polarization vision, for
      light polarization pollution, and for remote sensing are discussed.

PMID- 30118053
TI  - Depth of focus extension by filtering in the frequency domain in laser frequency
      shifted feedback imaging.
AB  - The depth of focus extension in optical imaging is of considerable interest. In
      this paper, a laser frequency-shifted feedback scanning imaging configuration is
      demonstrated whose depth of focus is greatly extended through numerical
      filtering. The transmission characteristics of the system are studied. The
      original image is acquired through a two-dimensional scanning point by point with
      the target placed on a defocused plane. Filtered in the frequency domain, images
      on any oriented plane can be refocused. The superior performances are presented
      by imaging a three-dimensional target, and the process of gradual refocusing is
      demonstrated. To obtain the maximum extension in the depth of defocus, a series
      of numerical experiments has been carried out, which reveals its depth of focus
      is capable of being extended to four times the length of the objective focus
      length. The fabulous performances can motivate three-dimensional surface profile
      measurement.

PMID- 30118054
TI  - Fiber coupling efficiency of Gaussian-Schell model beams in an ocean to fiber
      link with a Zernike tilt correction.
AB  - The fiber coupling efficiency of Gaussian-Schell model beams propagating through
      the oceanic turbulence of the Zernike tilt correction is studied. We derive the
      expression of the Zernike tilt corrected wave structure function. The numerical
      analysis reveals that a higher correction factor and spatial coherence of the
      laser beam increase the fiber coupling efficiency of the link. Our work shows
      that the increment of the fiber coupling efficiency caused by Zernike tilt
      correction under strong turbulence conditions is stronger than in the weak
      turbulence conditions, and the salinity fluctuation has a greater impact on it
      than temperature fluctuation does.

PMID- 30118055
TI  - Strain transferring mechanism analysis of the surface-bonded FBG sensor.
AB  - The mechanical analysis model of surface-bonded fiber Bragg grating (FBG) shear
      strain transfer is established in consideration of the linear viscoelastic effect
      of the adhesive layer, which is simplified as a standard linear solid model. And
      the strain transfer relation is acquired and validated by anchor bar uniaxial
      tension experiments. There is good correspondence between calculated values and
      experimental results. Finally, the influences of shear modulus, length and width
      of the adhesive layer, and thickness of the interlayer on the instantaneous and
      quasistatic strain transfer are analyzed by numerical simulation.

PMID- 30118056
TI  - Analysis of 90 day operation of the GINGERINO gyroscope.
AB  - Gyroscopes IN GEneral Relativity (GINGER) is a proposed experiment with the aim
      of measuring in a ground laboratory the gravitoelectric and gravitomagnetic
      effects foreseen by general relativity through an array of ring laser gyroscopes.
      GINGERINO is a square ring-laser prototype that has been built to investigate the
      level of noise inside the Gran Sasso underground laboratory. GINGERINO has shown
      the advantage of the underground location. Now it provides suitable data for
      geophysics and seismology. Since May 2017, it has continuously acquired data. The
      analysis of the first 90 days shows that the duty cycle is higher than 95%, and
      the quantum shot noise limit is of the order of 10-10(rad/s)/Hz. It is located in
      a seismically active area, and it recorded part of the central Italy earthquakes.
      Its high sensitivity in the frequency band of fraction of hertz makes it suitable
      for seismology studies. The main purpose of the present analysis is to
      investigate the long-term response of the apparatus. Simple and fast routines to
      suppress the disturbances coming from the laser have been developed. The Allan
      deviation of the raw data reaches some 10-6 after about 106  s of integration
      time, while the processed data show an improvement of 1 order of magnitude.
      Disturbances at the daily time scale are present in the processed data, and the
      expected signal induced by polar motion and solid Earth tides is covered by those
      disturbances.

PMID- 30118057
TI  - One symbol training receiver for the SPAD-based UVLC system.
AB  - For the long distance single photon avalanche diode (SPAD)-based underwater
      visible light communication (UVLC) system, the multiple-symbol union detection
      scheme is presented. However, an error floor curve of the bit-to-error ratio
      (BER) occurs and cannot vanish even though the transmitted power approaches
      infinity. In this paper, to solve the problems of error floor and channel
      estimation in the long distance SPAD-based UVLC system, we propose the one
      training symbol maximum likelihood (ML) detection receiver. First, we add one
      training symbol in the head of each frame to eliminate the error floor and ensure
      the reliable blind estimation of the long distance UVLC channel. Meanwhile, the
      training ML detection (TMLD) receiver is developed. And then, to improve the
      system performance, a training modified (TM) quasi-ML receiver with Anscombe root
      transformation is proposed. Compared to the traditional mean detection scheme of
      the SPAD receiver, the simulation results show that the proposed TM quasi-ML and
      TMLD schemes significantly improve the error-rate performance.

PMID- 30118058
TI  - NARX neural network model for strong resolution improvement in a distributed
      temperature sensor.
AB  - This paper proposes an approach to process the response of a distributed
      temperature sensor using a nonlinear autoregressive with external input neural
      network. The developed model is composed of three steps: extraction of
      characteristics, regression, and reconstruction of the signal. Such an approach
      is robust because it does not require knowledge of the characteristics of the
      signal; it has a reduction of data to be processed, resulting in a low processing
      time, besides the simultaneous improvement of spatial resolution and temperature.
      We obtain total correction of the temperature resolution and spatial resolution
      of 5 cm of the sensor.

PMID- 30118059
TI  - Preparation and quantitative characterization of polydimethylsiloxane optical
      phantoms with zinc-phthalocyanine dye absorbers.
AB  - We described a method for the preparation of polydimethylsiloxane (PDMS) phantoms
      to mimic the optical properties of biologic tissues at distinct wavelengths
      ranging from the visible to the near-infrared spectra. The present method for
      fabricating solid optical tissue phantoms using zinc-phthalocyanine chromophores
      has demonstrated high photostability with optical absorption coefficients up to
      1.0  mm-1, making this phantom proper with absorption bands ranging from 600 to
      850 nm. It also happens that the chromophore absorption coefficient is linear as
      a function of its concentration inside the previous optical window. The optical
      scattering properties were quantitatively selected by adding TiO2 particle
      concentrations to the PDMS phantom. Thus, the quantitative optical properties of
      absorption and scattering for a large-batch fabrication were demonstrated, making
      the zinc-phthalocyanine phantoms suitable for use as a reference standard.

PMID- 30118060
TI  - Partial least squares regression calculation for quantitative analysis of metals
      submerged in water measured using laser-induced breakdown spectroscopy.
AB  - Effects of different parameters regarding partial least squares (PLS) regression
      analysis are investigated for quantitative analysis of water-submerged brass
      samples. The concentrations of Cu and Zn in various brass alloys were quantified
      using PLS, and the performance after different signal processing steps
      (normalization, smoothing, and background subtraction) and database segmentation
      by excitation temperature is compared. In addition, the effects of averaging
      numbers on the results are examined. From the results, normalization was found to
      be the most effective among three established signal processing methods. The
      effects of both peak and background fluctuations seen in the signals are reduced
      by normalization. It was found that temperature segmentation of the database in
      an appropriate range, which should be high enough for reliable peak detection,
      can further improve the accuracy of PLS calculations. The proposed method is
      applicable in real time, and can potentially be used for automated fast and
      accurate measurements of solids at oceanic pressures.

PMID- 30118061
TI  - Reflective EUVL tool design with generalized Gaussian constant mathematics.
AB  - This study aims to develop a systematic design procedure for extreme ultraviolet
      lithography tools. Through analysis using generalized Gaussian constants,
      relationships between optical properties and requirements can be obtained, and
      can be used to help ensure that optical system properties required for the tool
      are upheld during the design process. As verification of the design method, an
      eight-mirror 0.4 NA tool design has been demonstrated.

PMID- 30118062
TI  - Low-coherence interferometry for phase-sensitive measurement of optical rotation.
AB  - We present phase-sensitive measurement of optical rotation using spectral-domain
      and time-domain low-coherence interferometry. The method utilizes two
      decorrelated polarization states and simultaneous dual-channel detection provided
      by polarization-maintaining fiber-based implementation. The sample is placed
      between polarization optics to control and switch left- and right-handed circular
      states that experience the sample in forward and backward directions. Phase
      difference between two interferometric signals yields the optical rotation.
      Results from glucose and fructose samples are presented for validation.

PMID- 30118063
TI  - Peculiarities of acousto-optic interaction in biaxial crystal of alpha-iodic
      acid.
AB  - With the example of an alpha-iodic acid crystal, we demonstrate the unusual
      peculiarities of acousto-optic interaction in gyrotropic biaxial crystals. Basic
      attention is given to the most interesting cases of anisotropic diffraction in
      geometry, when the wave vector of ultrasound is directed almost orthogonally to
      one of the optical axes, and the directions of incident and diffracted light
      beams are close to the optical axis. It is shown that in this case a peculiar
      character of optical anisotropy originates unique variants of acousto-optic
      interaction that are fundamentally impossible in uniaxial crystals. A wide
      variety of frequency dependences of the Bragg angles allows choosing optimal
      configurations of crystal cuts for each specific acousto-optic device. The
      influence of the effect of optical activity on diffraction characteristics is
      examined as well.

PMID- 30118064
TI  - Vision measurement error analysis for nonlinear light refraction at high
      temperature.
AB  - For vision measurement at high temperature, pixel error from light refraction by
      high temperature is a problem that cannot be neglected. The refractive index
      distribution is nonlinear around the high-temperature component, leading to the
      light deflection. In this paper, the influence of measurement parameters on the
      deflection of imaging light and the accuracy after binocular reconstruction are
      systematically analyzed. The heat transfer theory is used to simulate the air
      temperature distribution near the measured component, and the corresponding
      refractive index distribution of air is obtained according to the refractive
      index formula. Then, the imaging measurement model of the nonlinear refractive
      index air medium for the high-temperature component is established to obtain the
      light deflection error. The binocular vision system reconstruction theory is
      applied to evaluate the measurement error between the theoretical reconstruction
      point and the object point. The influences of error sources, such as the
      temperature, optical wavelength, and camera parameters, are investigated
      systematically. It is found that temperature and base distance are the largest
      error sources on the final measurement error when the measured distance is fixed.

PMID- 30118065
TI  - Evolution mechanism of surface roughness during ion beam sputtering of fused
      silica.
AB  - Ultrasmooth surfaces with sub-nanometer roughness and low damage are a great
      challenge for optical fabrication. Ion beam sputtering (IBS) has obvious
      advantages on the improvement of surface quality and the removal of surface
      defects. However, surface defects with different properties and structures
      display different evolution laws during the IBS process, which affects the
      roughness change and needs classification studies. In this paper, classification
      experiments are carried out to study the surface topography evolution of plastic
      scratches, brittle scratches, and micro-particles during the IBS process. The
      plastic scratches and micro-particles can be removed, while the brittle scratches
      can be passivated, so that surface defects can be reduced and surface quality
      improved. The corresponding evolution mechanisms are discussed in depth, and we
      show that micro-topography characteristics and material properties are important
      factors affecting the evolution of surface topography. Through the summary of
      evolution laws of different surface states, the Gaussian distribution law of
      surface roughness is established. The evolution regularity and mechanism of
      surface roughness during the IBS process are expounded upon from the perspective
      of microscopic morphology, which lays a foundation for ultra-smooth surface
      manufacturing with low damage.

PMID- 30118066
TI  - 790  W incoherent beam combination of a Tm-doped fiber laser at 1941  nm using a
      3 * 1 signal combiner.
AB  - In this paper, we report on a high-power incoherent beam combination of three Tm
      doped fiber amplifiers at 1941 nm based on a 3*1 signal combiner. An output power
      of 790 W is achieved from the signal combiner with a slope efficiency of 52.2%
      with respect to the launched pump power and a beam quality factor M2 of 2.7. The
      beam quality factor is close to the theoretical limit of the 3*1 fiber combiner.
      The parameters of the amplifier are optimized to increase the laser efficiency.
      Our analyses show that this structure is sufficient to support kilowatt-level
      output power while maintaining the high beam quality.

PMID- 30118067
TI  - Super-resolution imaging properties of cascaded microsphere lenses.
AB  - In this paper, the imaging properties of a cascaded microsphere lens are studied.
      The cascaded microsphere lens consists of two lenses. A hexagonally close-packed
      960-nm-diameter array of polystyrene microspheres is used as the first lens. The
      second lens is a single silica microsphere with a diameter of about 5 MUm. A Blu
      ray disc is observed by both the cascaded microsphere lens and the single silica
      microsphere. Studies reveal that the magnification of the cascaded microsphere
      lens is about 1.4 times greater than that of the single silica microsphere, while
      the field of view of the cascaded microsphere lens, which is close to the
      diameter of the polystyrene microsphere, is decreased. The focal position of the
      cascaded lens microsphere must be close to the sample in order to observe it.

PMID- 30118068
TI  - Mirror-based flexible one-step calibration method of light-sectioning system for
      surface topography.
AB  - A flexible, easy-to-implement, one-step calibration method of the light
      sectioning system is proposed for surface topography using a mirror adapter. The
      calibration method employs an arbitrary non-planar object with feature points as
      a target. With the assistance of the mirror adapter, the real and the reflected
      images of calibration are spatially separated and captured by a camera. It is
      developed as a direct calculation (DC) method and a virtual camera (VC) method to
      optimize the full parameters of the system. The DC method estimates the relative
      rotation and translation, respectively, and the VC method regards the two images
      as captured by two cameras in a physical sense through image flipping. The
      parameters of the laser plane can be solved accordingly. A numerical simulation
      is performed to analyze the precision of these two methods. A three-dimensional
      (3D) toy and a mechanical element are measured to verify the validity in
      translation experiments.

PMID- 30118069
TI  - Dispersion-engineered microstructured optical fiber for mid-infrared
      supercontinuum generation.
AB  - Due to the large scientific and technical interest in the mid-infrared (MIR)
      spectral region, and the limitations of MIR light sources, we focus on the
      generation of a broad supercontinuum inside a short piece of As2Se3
      microstructured optical fiber (MOF) with a square lattice. This is accomplished
      by filling the holes in the innermost ring of the proposed MOF with Ge33As12Se55
      to produce ultraflat and near-zero dispersion. Simulations reveal that, by
      launching 100 fs input pulses centered at lambda0=6.2  MUm with a peak power of 2
      kW into the MOF, an optical spectrum as wide as 9.5 MUm will be achieved. This
      spectrum is a suitable source for MIR applications such as spectroscopy, food
      quality control, and gas sensing.

PMID- 30118070
TI  - Thermally induced chirp studies on spectral broadening of semiconductor laser
      diode arrays.
AB  - Spectral-width broadening has many factors. Diode lasers are not always
      monochromatic due to several broadening mechanisms, widening the energy
      distribution of emitted photons. In this paper, we report the two main factors
      affecting time average spectral-width broadening of a laser diode array (LDA)-a
      transient rise of the active region temperature of an LDA due to injection
      current, and the temperature and stress nonuniform distribution of different
      emitters within an LDA. We find that temperature and stress nonuniformity
      broadens the spectral width by almost 0.1-1.0 nm as a function of different
      operating conditions, while the thermally induced chirp that is attributed to
      injection current plays a more signification role in spectral-width broadening.

PMID- 30118071
TI  - Optical detection of acoustic waves with surface plasmons.
AB  - For broadband and sensitive detection of acoustic waves, the surface plasmon
      resonance (SPR) can be used, which responds to variations of dielectric
      properties in close proximity to a metal film supporting surface plasmon waves.
      When an acoustic wave is incident onto a receiving plate positioned within the
      penetration depth of the surface plasmons, it creates displacements of the
      surface of the plate and thus modulates the dielectric properties, affecting the
      SPR and the reflection of the incident light. Here we study characteristics and
      determine the optimal configuration of such an acousto-optical transducer with
      surface plasmons for efficient conversion of an acoustic signal into an optical
      one. We simulate the properties of this transducer and present estimates showing
      that it can have a large frequency bandwidth and high sensitivity.

PMID- 30118072
TI  - Class modal analysis of a thin multi-trench-assisted liquid-filled optical
      waveguide coupler for simultaneous multi-sensing applications.
AB  - In this paper, we present an analysis of, to the best of our knowledge, a novel
      class of the thin multi-trench-assisted optical coupler for multi-sensing of
      chemical detection. The design structure is an optical waveguide coupler
      consisting of closely coupled trenches filled with different liquids for chemical
      sensing. The refractive index profile of the coupler is allowed to vary due to
      the chemical filled in these trenches. The scalar finite difference method (FDM)
      is used to analyze the TE (s polarized) as well as TM (p polarized) modes, and
      thereafter propagate them along the structure through various trenched sections.
      We excite the structure with the eigenmode profile, which can be well
      approximated by the Gaussian shape pulse. The trenches with different chemicals
      and separation between them are well demonstrated in several examples. The main
      finding of this paper is that the coupling period of the structure can be changed
      by altering the refractive index of the trench region. In the FDM analysis, we
      have used the variable discretization step for better accuracy of these results.
      A new approach based on a thin multi-trench-assisted optical coupler scheme to
      analyze and design the chemical sensor is then proposed for the first time, to
      the best of our knowledge, for the detection of adulteration present in, for
      example, beverages, and in the medical industry.

PMID- 30118073
TI  - Four-wave mixing in Ar-filled hollow core bandgap photonic crystal fiber.
AB  - To study the four-wave mixing (FWM) effect and wavelength conversion in a hollow
      core bandgap photonic crystal fiber filled with Ar, we conducted an experiment
      using a femtosecond laser with the pulse width of 120 fs, a repetition rate of 76
      MHz, and tunable central wavelength from 760 to 980 nm. It is observed that new
      spectra are generated in both sides of the pump at a special wavelength, which
      can exactly satisfy the phase matching conditions of FWM. Combining experimental
      results with theoretical analysis, we find that the experimental phenomenon is
      mainly caused by FWM, and some other nonlinear phase effects, such as self-phase
      modulation, stimulated Raman scattering, and the soliton effect, have also
      occurred in this nonlinear process.

PMID- 30118074
TI  - Evaluation of laser frequency offset locking using an electrical delay line.
AB  - Frequency offset locking between two Nd:YAG lasers is performed using frequency
      locking with an electrical delay line. The relative frequency instability of the
      offset locking is measured to be 3.5*10-12 for an averaging time of 1 s, which is
      approximately 77 times smaller than that of the free-running case. The frequency
      instability of the frequency locking is compared to that of the phase locking
      between the two Nd:YAG lasers. Furthermore, a compact solid-state laser is
      frequency locked to an optical frequency comb with a frequency instability of
      8.2*10-11 for an averaging time of 1 s, which is improved by approximately 20
      times, with respect to the free-running case. The offset-locking scheme using a
      delay line is useful for various applications including a research on quantum
      optics, interferometric measurements, and experiments involving laser cooling,
      such as an optical lattice clock.

PMID- 30118075
TI  - High loop rate adaptive optics flood illumination ophthalmoscope with structured
      illumination capability.
AB  - The design and performance of an adaptive optics flood illumination
      ophthalmoscope (AO-FIO) platform, based on eye motion and dynamic aberrations
      experimental analysis, are described. The system incorporates a custom-built real
      time controller, enabling up to 70 Hz loop rate without jitter, and an AO
      corrected illumination capable of projecting high-resolution features in the
      retina. Wide-field (2.7 degrees *5.4 degrees ) and distortionless images from
      vessel walls, capillaries, and the lamina cribrosa are obtained with an enhanced
      contrast and signal-to-noise ratio, thanks to careful control of AO parameters.
      The high spatial and temporal resolution (image acquisition up to 200 Hz)
      performance achieved by this platform enables the visualization of vessel
      deformation and blood flow. This system opens up the prospect of a return to
      favor of flood illumination adaptive optics systems provided that its high pixel
      rate and structured illumination capabilities are exploited.

PMID- 30118076
TI  - Modeling the longitudinal intensity pattern of diffraction resistant beams in
      stratified media.
AB  - In this paper, we study the propagation of the frozen wave (FW)-type beams
      through non-absorbing stratified media and develop a theoretical method capable
      of providing the desired spatially shaped diffraction-resistant beam in the last
      material medium. In this context, we also develop a matrix method to deal with
      stratified media with a large number of layers. Additionally, we undertake some
      discussion about minimizing reflection of the incident FW beam on the first
      material interface by using thin films. Our results show that it is indeed
      possible to obtain the control, on demand, of the longitudinal intensity pattern
      of a diffraction-resistant beam, even after it undergoes multiple reflections and
      transmissions at the layer interfaces. Remote sensing, medical and military
      applications, noninvasive optical measurements, etc., are some fields that can
      benefit from the method here proposed.

PMID- 30118077
TI  - Twin-image reduction method using a diffuser for phase imaging in-line digital
      holography.
AB  - Phase imaging by digital holography is widely used. An in-line optical setup is
      preferable for a practical use. A twin image, however, is a serious obstacle to
      achievement of high-quality phase imaging in in-line digital holography. For in
      line digital holography, a time-division phase-shifting method or a wave
      splitting phase-shifting method is used to eliminate the twin image. The former
      requires multiple exposures, and the latter requires specially designed optical
      elements. To solve these problems, a twin-image reduction method using a diffuser
      is proposed. In the proposed method, recording a digital hologram using a
      diffuser and signal processing enable reduction of the twin image on a
      reconstructed plane. A preliminary experimental result confirms the feasibility
      of the proposed method.

PMID- 30118078
TI  - Effect of solvent film and zeta potential on interfacial interactions during
      optical glass polishing.
AB  - The deployment of polishing slurry is one of the important research topics in the
      field of chemical-mechanical polishing. It is expected that technological
      breakthroughs in this process will lead to an improvement of the surface quality
      of fabricated optical components. In this investigation, we added several types
      of electrolytes into cerium oxide polishing slurries and evaluated their
      influence on the material removal rate (MRR) and surface roughness (Sa) during K9
      glass polishing. Furthermore, we investigated their influence on the zeta
      potential, particle size distribution, and suspension stability of the slurries.
      The results show that the introduction of an electrolyte into the polishing
      slurry changes not only the zeta potential of the ceria particle surface, but
      also the type and thickness of the deposited solvent film. The presence of a
      hydrophilic solvent film results in repulsion between individual particles and
      between the particles and the glass surface. However, a hydrophobic solvent film
      enhances the attraction between individual particles and between the particles
      and the glass surface. Moreover, thicker solvation films correspond to a greater
      force. This has a great impact on the interfacial interaction between the
      particles and the glass surface during the polishing process. The presence of the
      hydrophobic solvent film results in a high MRR, while the hydrophilic solvent
      film is associated with low Sa. In this paper, the interaction mechanisms of the
      abrasive particles and the glass interface during the polishing process are
      elucidated by considering the zeta potential and the solvent film type. In
      addition, a method for reducing the resulting Sa after glass polishing is
      proposed.

PMID- 30118079
TI  - Femtosecond, two-photon, laser-induced fluorescence (TP-LIF) measurement of CO in
      high-pressure flames.
AB  - Quantitative, kiloherz-rate measurement of carbon monoxide mole fractions by
      femtosecond two-photon, laser-induced fluorescence (TP-LIF) was demonstrated in
      high-pressure, luminous flames over a range of fuel-air ratios. Femtosecond
      excitation at 230.1 nm was used to pump CO two-photon rovibrational X1Sigma+
      >B1Sigma+ transitions in the Hopfield-Birge system and avoid photolytic
      interferences with excitation irradiance ~1.7*1010  W/cm2. The effects of
      excitation wavelength, detection scheme, and potential sources of de-excitation
      were also assessed to optimize the signal-to-background and signal-to-noise
      ratios and achieve excellent agreement with theoretically predicted CO mole
      fractions at low and high pressure.

PMID- 30118080
TI  - Optical modeling of superconducting nanowire single photon detectors using the
      transfer matrix method: publisher's note.
AB  - This publisher's note amends the Funding and Acknowledgment sections in Appl.
      Opt.57, 4872 (2018)APOPAI0003-693510.1364/AO.57.004872.

PMID- 30118081
TI  - Design of a high-numerical-aperture extreme ultraviolet lithography illumination
      system.
AB  - High-numerical-aperture (NA) anamorphic imaging projection objectives are the
      industrial choice for extreme ultraviolet lithography under the advanced
      technology node. The illumination system has to match the elliptical entrance
      pupil of the high-NA projector. In this paper, an illumination system suitable
      for a high-NA anamorphic projection objective is designed. The two-mirror relay
      system of the illumination system is designed by a two-stage process. The first
      order initial configuration with spherical surfaces is calculated by a method
      based on matrix optics. Then after tilting and decentering the two spherical
      surfaces to eliminate obscuration, the two mirror surfaces are fitted into conic
      surfaces. To realize many different illumination modes, a facet mirror matching
      method based on combinatorial optimization is proposed to allocate the mapping
      relationship between the field and pupil facets under different illumination
      modes. Simulation results of the system illumination uniformity show the system
      can achieve high uniformity on the reticle under different illumination modes.

PMID- 30118082
TI  - 1.6  MHz scanning rate direct absorption temperature measurements using a single
      vertical-cavity surface-emitting laser diode.
AB  - This paper presents 1.6 MHz scan rate, non-intrusive, time-resolved temperature
      measurements of a normal shock reflection from a plane end wall within a shock
      tube. A vertical-cavity surface-emitting laser (VCSEL) was used to conduct
      tunable diode laser absorption spectroscopy with water vapor as the probe
      species. The results are compared with analytical predictions. Temperatures
      measured with this technique agree within a single-scan standard deviation of +/
      33  K with calculated temperatures at a VCSEL modulation frequency of 800 kHz,
      which is sufficiently rapid enough to be used to investigate highly transient
      shock wave interaction processes.

PMID- 30118083
TI  - Optimized pupil-plane phase masks for high-contrast imaging.
AB  - A differential evolution algorithm (DEA) is shown to improve the design of phase
      only pupil plane masks for imaging in the presence of a high-intensity point
      source. Strehl and suppression ratio metrics for various phase basis functions
      were experimentally and numerically calculated. Experiments performed with a
      spatial light modulator demonstrated 100 times suppression of the peak intensity.
      The Strehl ratio was found to be higher for the DEA masks compared to the
      individual phase basis function.

PMID- 30118084
TI  - How the alternating degeneracy in rotational Raman spectra of CO2 and C2H2
      reveals the vibrational temperature.
AB  - The contribution of higher vibrational levels to the rotational spectrum of
      linear polyatomic molecules with a center of symmetry (CO2 and C2H2) is assessed.
      An apparent nuclear degeneracy is analytically formulated by vibrational
      averaging and compared to numerical averaging over vibrational levels. It enables
      inferring the vibrational temperature of the bending and asymmetric stretching
      modes from the ratio of even to odd peaks in the rotational Raman spectrum. The
      contribution from higher vibrational levels is already observable at room
      temperature as g~e/o=0.96/0.04 for CO2 and g~e/o=1.16/2.84 for C2H2. The use of
      the apparent degeneracy to account for higher vibrational levels is demonstrated
      on spectra measured for a CO2 microwave plasma in the temperature range of 300
      3500 K, and shown to be valid up to 1500 K.

PMID- 30118085
TI  - Regression-based technique for improved optical rangefinding using tunable focus
      lenses.
AB  - In this paper, we present a novel method of target range estimation by tuning the
      spot size of a Gaussian beam at the plane of a reflective target. The beam spot
      size tuning is achieved through the use of a tunable focus lens (TFL). Using a
      carefully aligned sensor assembly, the diameter of the reflected beam is recorded
      at the plane of an imaging detector for different TFL focal length settings. This
      dataset is then used to estimate the distance of the target from the TFL. The
      proposed rangefinder is compact and requires minimal post-data-acquisition signal
      processing resulting in a fast response time compared to other spatial signal
      processing-based sensor designs. The estimation of target distance through a
      multiple data-point measurement dataset also ensures that the proposed method is
      robust to errors associated with obtaining range estimates from a single
      measurement data point. Experimental results demonstrate an excellent agreement
      with theory. With our proposed estimation method, we show a significant
      improvement in the measurement dynamic range of the sensor as well as its
      resolution compared to similar sensing schemes in prior art. We also
      experimentally demonstrate the possibility to extend the measurement dynamic
      range by incorporating a bias lens of a fixed focal length with the sensor
      module. The proposed sensor module is electronically controlled and consequently
      can be fully automated and compactly packaged with the use of commercially
      available miniature optical components.

PMID- 30118086
TI  - Determination of the refractive index and Abbe number of glass of spherical
      lenses.
AB  - The paper deals with the problem of determination of basic parameters of unknown
      spherical lenses, namely their radii of curvature, thicknesses, and refractive
      indices of materials, for example, optical glasses, from which these lenses are
      made. Four methods are proposed to obtain these parameters and mathematical
      relations are derived that allow us to determine the refractive index and Abbe
      number of lens material based on the measured radius values, the thickness, and
      the position of the focal point or the focal length.

PMID- 30118087
TI  - Propagation properties of hypergeometric-Gaussian type-II beams through the
      quadratic-index medium.
AB  - The analytical expressions of hypergeometric-Gaussian type-II (HyGG-II) beams
      propagating in the quadratic-index medium are deduced based on the ABCD optical
      transformation matrix method. The propagation properties of HyGG-II beams in the
      quadratic-index medium are numerically and theoretically analyzed in detail. The
      intensity distribution and the second-order moment-based beam width vary
      periodically when the HyGG-II beams pass through the quadratic-index medium. The
      interactions of two HyGG-II beams are also discussed graphically.

PMID- 30118088
TI  - Two-step carrier-wave stitching method for aspheric and freeform surface
      measurement with a standard spherical interferometer.
AB  - Measurement of aspheric and freeform surfaces remains challenging due to the
      various shapes of the surface under test (SUT), especially when the SUT has a
      large aperture and strong deviation from the spherical surface. This paper
      proposes a two-step carrier-wave stitching method to enlarge the measurement
      bandwidth of a digital Moire interferometry. Then, measurements of aspheric and
      freeform surfaces with a standard spherical interferometer without a phase
      shifting mechanism are demonstrated. Experimental results with a root-mean-square
      repeatability of better than 1/200lambda present good consistency to UA3P contact
      measurement results. Further simulation results with different residual
      wavefronts confirm measurement accuracies of peak-to-valley value of 10-3lambda.
      The method is effective for large residual wavefronts and thus has potential for
      flexible measurement of aspheric and freeform surfaces.

PMID- 30118089
TI  - Tunable 360 degrees  microwave photonic multichannel phase shifter with frequency
      quadrupling.
AB  - In this paper, a photonic scheme to generate a frequency-quadrupled microwave
      signal with full-range 360 degrees  tunable phase shift is proposed and
      experimentally demonstrated. Pure +/-2nd-order sidebands with the carrier
      suppressed are generated by a dual-parallel Mach-Zehnder modulator. The two
      sidebands are separated by a fiber Bragg grating with the polarization state of
      one sideband rotated by 90 deg via a Faraday rotating mirror and then recombined
      to obtain a pair of orthogonally polarized wavelengths. The two orthogonally
      polarized optical sidebands are aligned into the same polarization direction by
      using a polarizer (Pol). Finally, a radio frequency (RF) signal with frequency
      quadrupling of a local oscillator signal is obtained by beating the +/-2nd-order
      sidebands at a photodetector. The phase theta of the frequency-quadruped RF
      signal can be independently and arbitrarily adjusted from 0 degrees  to 360
      degrees  through control of the polarization direction. Experiments are carried
      out to demonstrate the scheme, and frequency-quadrupled microwave signals at 12
      GHz and 16 GHz are generated. A continuous phase shift from 0 degrees  to 360
      degrees  of the frequency-quadrupled signal at 12 GHz is also verified. The
      proposed scheme not only has the merits of large operation bandwidth and simple
      structure but also can be extended to multi-channel applications.

PMID- 30118091
TI  - Compact multichannel infrared camera integrated in an operational detector dewar
      cooler assembly.
AB  - We present an ultracompact infrared cryogenic camera integrated inside a standard
      Sofradir's detector dewar cooler assembly (DDCA) whose field of view is equal to
      120 degrees . The multichannel optical architecture produces four nonredundant
      images on a single SCORPIO detector with a pixel pitch of 15 MUm. This
      ultraminiaturized optical system brings a very low additional optical and
      mechanical mass to be cooled in the DDCA: the cool-down time is comparable to an
      equivalent DDCA without an imagery function. Limiting the number of channels is
      necessary to keep the highest number of resolved points in the final image.
      However, optical tolerances lead to irregular shifts between the channels. This
      paper discusses the limits of multichannel architectures. With an image
      processing algorithm, the four images produced by the camera are combined to
      process a single full-resolution image with an equivalent sampling pitch equal to
      7.5 MUm. Experimental measurements on the modulation transfer function and noise
      equivalent temperature difference show that this camera achieves good optical
      performance.

PMID- 30118090
TI  - CO2 laser-written long-period fiber grating with a high diffractive order
      cladding mode near the turning point.
AB  - We demonstrate the fabrication of a long-period fiber grating (LPFG) in a boron
      doped single-mode fiber with a high-diffractive-order cladding mode (HDCM) near
      the turning point (TP). The simulations show that an LPFG with less than 0.2 duty
      cycles can couple light to the HDCM. An LPFG with a period of more than 400 MUm
      can achieve strong mode coupling between the fundamental mode and the HDCM near
      the TP. The effect of the external refractive index on the transmission spectrum
      of a LPFG with different grating periods is investigated by simulations and
      experiments. With an increase in grating period, the spectral dip corresponding
      to the HDCM travels faster than the conventional dip, and overlapped dips appear
      in the transmission spectrum. High sensitivities of up to 13,497.7  nm/RIU and
      0.77  nm/ degrees C of, respectively, RI and temperature sensing can be achieved.
      Such LPFGs could be potentially used as optical filters and high-sensitivity
      sensors.

PMID- 30118092
TI  - Multi-wavelength unidirectional forward scattering in the visible range in an all
      dielectric silicon hollow nanodisk.
AB  - A dielectric nanoantenna with a relatively large refractive index possesses
      magnetodielectric properties that can offer the unique opportunity to tailor
      unidirectional scattering. Herein, we demonstrate that the interference from
      electric and magnetic multipoles in the silicon hollow nanodisk suppresses
      backscattering and enhances forward scattering of light. This concept is
      implemented to design a lossless dielectric collector element, which constitutes
      an enabling technology for applications that require backward scattering
      suppression, such as nanoantennas and photovoltaic devices.

PMID- 30118093
TI  - Precision fringe period metrology using an LSQ sine fit algorithm.
AB  - High-precision grating fabrication is a precondition of grating-based
      displacement measurement techniques. Likewise, the value of high-precision fringe
      period is an essential parameter in the grating fabrication process, especially
      in scanning beam interference lithography. In this paper, a procedure for
      measuring the fringe periods of interference beams is introduced. The procedure
      includes signal acquisition and signal processing. The precisions of both the
      configuration for acquisition and the algorithm for processing are discussed.
      Experiments for fringe period measurement are also conducted, and an average
      value of 564.374 nm with a standard deviation of 1.5 pm is obtained, reaching a
      repeatability of 2.6 ppm. The value of precision period lays a solid foundation
      for the fabrication of high-precision gratings.

PMID- 30118094
TI  - Modeling variation coefficient of wave-induced underwater irradiance for clear
      ocean and its application to find the optimal detector size.
AB  - In measuring the coefficient of variation (CV) of underwater wave-induced
      sunlight irradiance, the spatial integration of irradiance signals due to the
      finite aperture size of an irradiance detector usually causes underestimation of
      the measured variance. Because this spatial integration effect is strongly
      coupled with ocean wave features, inherent optical properties (IOPs) of water,
      and atmospheric radiance conditions, direct deconvolution techniques from
      measured irradiance signals can lead to serious signal-to-noise degradation in a
      noisy upper ocean. On the other hand, choosing a small detector to guarantee CV
      accuracy is expensive. We address the intrinsic dependence of the CV on the
      detector size and choice of optimal detector size for measuring irradiance
      variability in a turbid ocean environment. We present a new theoretical model to
      directly obtain the form of the CV of the wave-induced scalar irradiance as the
      function of the detector size, ocean surface wave parameters, and IOPs of ocean
      water. The model is derived under the small-angle scattering approximation and
      the first-order assumption of Snell's law and Fresnel transmission coefficient.
      We demonstrate the validity and efficacy of the model for weakly roughened
      Gaussian ocean surface conditions, by comparison with Monte Carlo radiative
      transfer simulations. The model shows that the CV of wave-induced irradiance
      reaches an asymptotic with decreasing the detector size, thereby providing an
      optimal or maximum detector size for given IOP and environmental conditions.

PMID- 30118095
TI  - Optical nonlinearities in LiKB4O7-Ag2O and LiKB4O7-Ag2O-Gd2O3 glasses containing
      Ag nanoparticles.
AB  - The results on optical studies of LiKB4O7-Ag2O and LiKB4O7-Ag2O-Gd2O3 glasses
      containing Ag nanoparticles formed during annealing in vacuum and air are
      presented. Strong bands that appear in optical transmission spectra of the
      samples correspond to plasmon excitations associated with Ag nanoparticles. The
      average radius of Ag nanoparticles was retrieved from FWHM of the plasmon bands
      and found to be 1.8-3.8 nm. Nonlinear optical properties of the glasses were
      studied by the single-beam Z-scan technique. In particular, influence of Ag
      nanoparticles on nonlinear refraction n2 and nonlinear absorption beta
      coefficients was investigated.

PMID- 30118096
TI  - Simulation of penetration depth of Bessel beams for multifocal optical coherence
      tomography.
AB  - Multifocal Bessel beam optical coherence tomography (MBOCT) combines the
      advantages of Bessel beam OCT and multifocal OCT to increase imaging depth. For
      MBOCT, the penetration depth of the Bessel beam in highly scattering biological
      tissue limits the final imaging depth. In this paper, we theoretically analyze
      the penetration depth of the Bessel beams with different parameters to explore
      which kind of Bessel beam is more suitable for MBOCT in a scattering medium. The
      finite-difference time-domain method is used to simulate the field distribution
      of Bessel beams in the medium. We find that the MBOCT for more focus based on a
      Bessel beam with a smaller Fresnel number N has higher penetration depth and
      light intensity when its lateral resolution is fixed. Moreover, the Bessel beam
      with N reversely closer to unity is more advantageous for penetrating the highly
      scattering medium for a certain imaging depth, and the Bessel beam has larger
      penetration depth when its lateral size is close to the size of the object to be
      imaged.

PMID- 30118097
TI  - Impulse response modeling for underwater optical wireless channels.
AB  - In underwater optical wireless communication (UOWC) channels, impulse response is
      widely used to describe the temporal dispersion of the received signals. In this
      paper, we propose a new function to model the impulse response in most realistic
      cases in UOWC channels. By exploiting the inherent properties of such channels,
      our newly proposed model is superior to the conventional weighted double gamma
      functions (WDGF) model in explaining the behavior of the channel. We use Monte
      Carlo simulation to verify that our newly proposed model has a better accuracy of
      numerical fitting in most cases. Therefore, this new modeling approach offers a
      more convenient way to evaluate the performance of different kinds of UOWC
      channels.

PMID- 30118098
TI  - Analytical model for active racetrack resonators with intracavity reflections and
      its application in Fano resonance tailoring.
AB  - We present an analytical model for estimating the spectral properties of an
      active racetrack resonator/waveguide system. Under reasonable approximations, we
      show that the transfer function can be approximated by a rational function, the
      coefficients of which are determined by the parameters of the structure. The
      model takes into account intracavity reflections that can provide additional
      degrees of freedom in the design. We identify conditions under which asymmetric
      transitions around a spectral peak can occur, which are characteristic of Fano
      type resonances. The accuracy of our model is verified by rigorous transfer
      matrix numerical simulations. We also discuss how the model can be applied for
      tailoring the transfer function in order to obtain sharper transitions from the
      spectral peaks to the minima in order for the structure to be used for sensing
      applications.

PMID- 30118099
TI  - Single-shot phase retrieval based on beam splitting.
AB  - A kind of beam-splitting-based single-shot phase retrieval is proposed, where the
      transmitted field of a sample to be observed is diffracted into many replicas by
      a Dammann grating and then incident on a weakly scattering phase plate with a
      known structure, and the exiting beams propagate roughly along their original
      directions and form a diffraction pattern array on the detector. All sub
      diffraction patterns isolated with each other were recorded with a single
      measurement, and the complex amplitude of the radiation incident on the grating
      and accordingly transmitted from the sample can be iteratively reconstructed from
      the recorded diffraction pattern array. Since the weakly scattering plate is
      accurately measured in advance, fast convergence and high accuracy can be
      achieved with a small number of sub-diffraction patterns. The feasibility of this
      proposed method is verified with experiments using visible light.

PMID- 30118100
TI  - Differential interference contrast microscopy for cells using hard x-ray
      holography.
AB  - We propose a differential interference contrast method for cells using hard x-ray
      Gabor holography and knife-edge filtering in the spatial frequency domain,
      without relying on beam shearing. A phase object is holographically recorded and
      reconstructed by computer. Interference between the wavefronts of zeroth order
      weighted by ejpi/2 in the positive frequency region produces a dark image.
      Similarly, interference between the wavefronts of the zeroth order weighted by
      ej3pi/2 in the negative frequency region produces a bright image. By adding these
      two intensity distributions, good quality phase-contrast images of 8-MUm-diameter
      polystyrene beads and human HeLa cells were obtained.

PMID- 30118101
TI  - Simultaneous measurement of phase transmission and birefringence of an object
      under test.
AB  - This paper presents a novel interferometric method for the simultaneous spatially
      resolved analysis of an object under test regarding the phase transmission
      function and the magnitude and orientation of the (uniaxial) birefringence. The
      measurement strategy is based on variations of the phase and polarization and
      processing the interference patterns so obtained. With this method, which is very
      similar to the classical phase-shifting interferometry, a complete analysis of
      birefringent properties of the object and its impact on the phase of the incoming
      light can be done in one measurement cycle. The theoretical description of the
      investigated methods and their experimental implementation are presented.

PMID- 30118102
TI  - Aberration correction in holographic optical tweezers using a high-order optical
      vortex: publisher's note.
AB  - This publisher's note identifies an error in the author affiliations of Appl.
      Opt.57, 3618 (2018)APOPAI0003-693510.1364/AO.57.003618.

PMID- 30118103
TI  - Concept for maritime near-surface surveillance using water Raman scattering.
AB  - We discuss a maritime surveillance and detection concept based on Raman
      scattering of water molecules. Using a range-gated scanning lidar that detects
      Raman scattered photons from water, the absence or change of signal indicates the
      presence of a non-water object. With sufficient spatial resolution, a two
      dimensional outline of the object can be generated by the scanning lidar. Because
      Raman scattering is an inelastic process with a relatively large wavelength shift
      for water, this concept avoids the often problematic elastic scattering for
      objects at or very close to the water surface or from the bottom surface for
      shallow waters. The maximum detection depth for this concept is limited by the
      attenuation of the excitation and return Raman light in water. If excitation in
      the UV is used, fluorescence can be used for discrimination between organic and
      non-organic objects. In this paper, we present a lidar model for this concept and
      discuss results of proof-of-concept measurements. Using published cross section
      values, the model and measurements are in reasonable agreement and show that a
      sufficient number of Raman photons can be generated for modest lidar parameters
      to make this concept useful for near-surface detection.

PMID- 30118104
TI  - Photoacoustic imaging of lamina cribrosa microcapillaries in porcine eyes.
AB  - Due to the embedded nature of the lamina cribrosa (LC) microcapillary network,
      conventional imaging techniques have failed to obtain the high-resolution images
      needed to assess the perfusion state of the LC. In this study, both optical
      resolution (OR) and acoustic resolution (AR) photoacoustic microscopy (PAM)
      techniques were used to obtain static and dynamic information about LC perfusion
      in ex vivo porcine eyes. The OR-PAM system could resolve a perfused LC
      microcapillary network with a lateral resolution of 4.2 MUm and also provided
      good depth information (33 MUm axial resolution) to visualize through-thickness
      vascular variations. The AR-PAM system was capable of detecting time-dependent
      perfusion variations. This study represents the first step towards using an
      emerging imaging modality (PAM) to study the LC's perfusion, which could be a
      basis for further investigation of the hemodynamic aspects of glaucomatous optic
      neuropathy.

PMID- 30118105
TI  - Optical modeling of superconducting nanowire single photon detectors using the
      transfer matrix method.
AB  - We present optical modeling of superconducting nanowire single photon detector
      devices using an analytical approach based on the transfer matrix method. We find
      that the optimal dielectric layer thicknesses vary slightly with the thickness
      and fill factor of the NbN layer and explore novel device geometries that can be
      described as a stack of thin films, such as devices on multilayered substrates,
      free-standing membranes, and optical fiber facets. In addition, the analytical
      results here show the importance of accounting for coherence correctly when an
      integrated cavity is included in the device structure and the relative
      insignificance of an anti-reflection coating in most cases.

PMID- 30118106
TI  - Method for defect contour extraction in terahertz non-destructive testing
      conducted with a raster-scan THz imaging system.
AB  - In this paper, a neoteric algorithm based on a two-dimensional continuous wavelet
      transform is developed to get the defect contour in the terahertz (THz) non
      destructive testing result obtained from a raster-scan frequency-modulated
      continuous-wave (FMCW) THz imaging system. In order to prove the method's
      validity, an experiment is carried out. The result of the experiment shows that
      the method allows one to extract the defect contour from the THz FMCW
      interference with severe stripe noises. Moreover, the relative error of defect
      area between the actual value and that obtained from the extracted defect contour
      is no more than 3.03%. This means that the method provided an effective and exact
      way to extract a defect contour in THz FMCW interference.

PMID- 30118107
TI  - Adaptive filter design via a gradient thresholding algorithm for compressive
      spectral imaging.
AB  - Sensing a spectral image data cube has traditionally been a time-consuming task
      since it requires a scanning process. In contrast, compressive spectral imaging
      (CSI) has attracted widespread interest since it requires fewer samples than
      scanning systems to acquire the data cube, thus improving the sensing speed. CSI
      captures linear projections of the scene, and then a reconstruction algorithm
      estimates the underlying scene. One notable CSI architecture is the color coded
      aperture snapshot spectral imager (C-CASSI), which employs pixelated filter
      arrays as the coding patterns to spatially and spectrally encode the incoming
      light. Up to date works on C-CASSI have used non-adaptive color coded apertures.
      Non-adaptive sampling ignores prior information about the signal to design the
      coding patterns. Therefore, this work proposes a method to adaptively design the
      color coded aperture, such that the quality of image reconstruction is improved.
      In more detail, this work introduces a gradient thresholding algorithm, which
      computes the consecutive color coded aperture from a rapidly reconstructed low
      resolution version of the data cube. The successive adaptive patterns enable
      recovering a data cube in the presence of Gaussian noise with higher image
      quality. Real reconstructions and simulations evidence an improvement of up to 3
      dB in the quality of image reconstruction of the proposed method in comparison
      with state-of-the-art non-adaptive techniques.

PMID- 30118108
TI  - Reference-plane-based fast pixel-by-pixel absolute phase retrieval for height
      measurement.
AB  - Absolute phase retrieval is essential for height measurement in digital fringe
      projection. However, projections of additional structured patterns that are
      normally required for phase unwrapping increase the measurement complexity. In
      this paper, we propose two reference-plane-based pixel-by-pixel absolute phase
      retrieval techniques with as few projections as possible, suitable for different
      object depth ranges. The wrapped phase on the object is absolutely unwrapped by
      referring just to the absolute phase map on the reference plane. Single-frequency
      absolute phase retrieval with one-reference-plane-based calibration is first
      proposed for objects within a height limit that equals a calibrated system
      constant. To extend the measurement depth range, dual-frequency absolute phase
      retrieval with two parallel reference planes is further proposed. The additional
      low frequency is used to choose the unwrapping reference from the two reference
      plane phases for unwrapping the high-frequency phase. Moreover, the proposed
      techniques are capable of high-frequency absolute phase unwrapping for objects
      with step-height surface discontinuities. Experiments have been conducted to
      demonstrate the efficiency of the proposed two techniques.

PMID- 30118109
TI  - Birefringence measurements of diamond space-variant subwavelength gratings.
AB  - Subwavelength gratings are gratings with periods smaller than the incident
      wavelength. They possess form birefringence, which depends on the grating
      parameters. This paper presents the results of an experimental method designed to
      measure the birefringent properties of diamond subwavelength gratings in the mid
      infrared. The method consists of monitoring the intensity transmitted through one
      polarizer, a subwavelength grating, and a second polarizer for various
      orientations of the first polarizer. By fitting the intensity variation as a
      function of the orientation of the first polarizer, one can compute the phase
      shift induced by the grating, its local fast axis orientation, and the ratio of
      the transverse electric and transverse magnetic transmission efficiencies. The
      paper describes the method principle and its mathematical model. Then, several
      numerical simulations of different subwavelength gratings are presented and their
      results are discussed. Finally, the optical setup is described and the
      measurements of one subwavelength grating are displayed and compared with the
      values expected from the manufacturing process.

PMID- 30118110
TI  - Spectral reflectance estimation from one RGB image using self-interreflections in
      a concave object.
AB  - Light interreflections occurring in a concave object generate a color gradient
      that is characteristic of the object's spectral reflectance. In this paper, we
      use this property in order to estimate the spectral reflectance of matte,
      uniformly colored, V-shaped surfaces from a single RGB image taken under
      directional lighting. First, simulations show that using one image of the concave
      object is equivalent to, and can even outperform, the state-of-the-art approaches
      based on three images taken under three lightings with different colors.
      Experiments on real images of folded papers were performed under unmeasured
      direct sunlight. The results show that our interreflection-based approach
      outperforms existing approaches, even when the latter are improved by a
      calibration step. The mathematical solution for the interreflection equation and
      the effect of surface parameters on the performance of the method are also
      discussed in this paper.

PMID- 30118111
TI  - Refractive index of adipose tissue and lipid droplet measured in wide spectral
      and temperature ranges.
AB  - This study presents refractive index measurements of human and porcine adipose
      tissues and lipid droplet content in the visible and near-infrared. The
      coefficients of the Sellmeier formula were calculated for approximation of tissue
      dispersion. For the first time, to the best of our knowledge, the phase
      transition temperatures and temperature increments dn/dT of adipose tissue were
      quantified for a wide wavelength range from 480 to 1550 nm and from room
      temperature up to 50 degrees C. For human abdominal adipose tissue, the
      refractive index increment averaged across all wavelengths is dn/dT=-(3.54+/
      0.15)*10-4 degrees C-1, for porcine tissue dn/dT=-7.92(0.74)*10-4 degrees C-1,
      and for porcine lipid droplet dn/dT=-6.01(0.29)*10-4 degrees C-1. Data available
      in literature for refractive indices of adipose tissues measured by different
      techniques are summarized and compared with the received data.

PMID- 30118112
TI  - Color digital hologram compression based on matching pursuit.
AB  - With the recent widespread interest for head-mounted displays applied to virtual
      or augmented reality, holography has been considered as an appealing technique
      for a revolutionary and natural 3D visualization system. However, due to the
      tremendous amount of data required by holograms and to the very different
      properties of holographic data compared to common imagery, compression of digital
      holograms is a highly challenging topic for researchers. In this study, we
      introduce a novel approach, to the best of our knowledge, for color hologram
      compression based on matching pursuit using an overcomplete Gabor's dictionary. A
      detailed framework, together with a GPU implementation, from hologram
      decomposition to bitstream generation, is studied, and the results are discussed
      and compared to existing hologram compression algorithms.

PMID- 30118113
TI  - Effect of noise-induced wavelength fluctuation in tunable diode lasers on narrow
      linewidth absorption measurements.
AB  - Tunable diode laser absorption spectroscopy is being widely used to make sensors
      for diagnostic purposes in various engineering applications. Since the wavelength
      of many diode lasers used in such sensors is sensitive to the driving current,
      even noise as small as a few MUArms in the driving current can cause a wavelength
      fluctuation of ~+/-0.5  pm, which is large enough to interfere with sensitive
      absorption measurements. Although these fluctuations are small, they can cause
      significant systematic error in measured absorption spectra in applications where
      the absorption line probed is narrow, as is the case for low-density hypersonic
      flows. As an example, at a pressure of 300 Pa and 297 K, the error in the full
      width at half-maximum was +/-6.5% in an absorption spectrum obtained using a
      system based on a vertical-cavity surface-emitting laser scanned at 10 kHz. This
      paper analyzes the effect of such systematic errors on measured temperature and
      velocity and suggests some remedial measures.

PMID- 30118114
TI  - A rationally designed Fe-tetrapyridophenazine complex: a promising precursor to a
      single-atom Fe catalyst for an efficient oxygen reduction reaction in high-power
      Zn-air cells.
AB  - The development of low-cost and highly efficient single-atom oxygen reduction
      catalysts to replace platinum for fuel cells and metal-air cells is highly
      desirable but remains challenging. Herein, we report the fabrication of isolated
      single-atom Fe anchored on porous nitrogen-doped carbon from the pyrolysis of a
      well-designed solely Fe-tetrapyridophenazine coordination complex. The N-rich
      bridging ligand, tetrapyridophenazine (tpphz) is first employed as a spatial
      isolation agent of Fe that suppresses its aggregation during high temperature
      pyrolysis, resulting in highly reactive and stable single-atom Fe ORR catalysts.
      The catalyst shows remarkable ORR activity with a half-wave potential of 0.863 V
      versus the reversible hydrogen electrode (RHE) (21 mV more positive than that of
      commercial 20 wt% Pt/C) and excellent durability in 0.1 M KOH. Whereas in acidic
      media, the Fe single atoms also demonstrate ORR activity comparable to and
      stability much higher than those of Pt/C. Notably, Zn-air cells made using the as
      prepared catalyst as the cathode provide a high open circuit voltage (1.53 V) and
      gravimetric energy density (947 W h kg-1), which are higher than commercial Pt/C
      based Zn-air cells (1.50 V and 828 W h kg-1). This work will open a new avenue to
      design single-atom catalysts for clean renewable energy storage and conversion
      devices.

PMID- 30118115
TI  - Photosensitiser-gold nanoparticle conjugates for photodynamic therapy of cancer.
AB  - Gold nanoparticles (AuNPs) have been extensively studied within biomedicine due
      to their biocompatibility and low toxicity. In particular, AuNPs have been widely
      used to deliver photosensitiser agents for photodynamic therapy (PDT) of cancer.
      Here we review the state-of-the-art for the functionalisation of the gold
      nanoparticle surface with both photosensitisers and targeting ligands for the
      active targeting of cancer cell surface receptors. From the initial use of the
      AuNPs as a simple carrier of the photosensitiser for PDT, the field has
      significantly advanced to include: the use of PEGylated modification to provide
      aqueous compatibility and stealth properties for in vivo use; gold metal-surface
      enhanced singlet oxygen generation; functionalisation of the AuNP surface with
      biological ligands to specifically target over-expressed receptors on the surface
      of cancer cells and; the creation of nanorods and nanostars to enable combined
      PDT and photothermal therapies. These versatile AuNPs have significantly enhanced
      the efficacy of traditional photosensitisers for both in vitro and in vivo cancer
      therapy. From this review it is apparent that AuNPs have an important future in
      the treatment of cancer.

PMID- 30118116
TI  - Computational investigation of microgels: synthesis and effect of the
      microstructure on the deswelling behavior.
AB  - We present computer simulations of a realistic model of microgels. Unlike the
      regular network frameworks usually assumed in the simulation literature, we model
      and simulate a realistic and efficient synthesis route, mimicking cross-linking
      of functionalized chains inside a cavity. This model is inspired, e.g., by
      microfluidic fabrication of microgels from macromolecular precursors and is
      different from standard polymerization routes. The assembly of the chains is
      mediated by a low fraction of interchain crosslinks. The microgels are
      polydisperse in size and shape but globally spherical objects. In order to deeply
      understand the microgel structure and eventually improve the synthesis protocol
      we characterize their conformational properties and deswelling kinetics, and
      compare them with the results found for microgels obtained via underlying regular
      (diamond-like) structures. For the same molecular weight, monomer concentration
      and effective degree of cross-linking, the specific microstructure of the
      microgel has no significant effect on the locus of the volume phase transition
      (VPT). However, it strongly affects the deswelling kinetics, as revealed by a
      consistent analysis of the domain growth during the microgel collapse. Though
      both the disordered and the regular networks exhibit a similar early growth of
      the domains, an acceleration is observed in the regular network at the late stage
      of the collapse. Similar trends are found for the dynamic correlations coupled to
      the domain growth. As a consequence, the fast late processes for the domain
      growth and the dynamic correlations in the regular network are compensated, and
      the dynamic correlations follow a power-law dependence on the growing length
      scale that is independent of the microgel microstructure.

PMID- 30118117
TI  - A geometrical criterion for glass transition in soft-sphere fluids.
AB  - As glass-forming fluids become colder and denser, structural rearrangements
      become slow and eventually cease. For hard-sphere fluids, percolation of
      particles unable to change neighbors (T1-inactive particles) signals the glass
      transition. To investigate this geometrical criterion for mobility in soft-sphere
      systems, we simulate monodisperse fluids interacting with a generalized Weeks
      Chandler-Andersen (WCA) potential in metastable equilibrium, using our previously
      developed crystal-avoiding method. We find that the vanishing diffusivity as the
      glass transition is approached can be described by a power law below the onset
      temperature of super-Arrhenius behavior. By mapping the soft spheres to hard
      spheres based on mean collision energy, we find that the diffusivity versus
      effective volume fraction curves collapse onto the hard-sphere curve for all
      systems studied. We find that the onset of super-Arrhenius behavior and the MCT
      dynamic glass transition correlate well with temperature when the T1-inactive
      particles form clusters of two particles on average and when the T1-inactive
      clusters percolate the entire system, respectively. Our findings provide new
      insight into the structural origin of glassy dynamics.

PMID- 30118118
TI  - Rhodium-calix[4]pyrrole and rhodium-tetraphenyl porphyrin: preparation, surface
      grafting and their catalytic application in nitro-benzene reduction.
AB  - Rhodium containing macromolecules calix[4]pyrrole (RhCP) and tetraphenyl
      porphyrin (RhTPP) were prepared and grafted on the surface of functionalised
      molecular sieve materials. 1H and 13C NMR, CHNS and mass spectral analyses were
      used for the structural elucidation of homogeneous organometallic complexes.1H
      NMR and CHNS analyses confirm the formation of calix[4]pyrrole (CP) and
      tetraphenyl porphyrin (TPP). The introduction of rhodium ions into the
      macromolecule is well evident from the disappearance of the 1H NMR signal
      characteristic of N-H proton (7.1 ppm in CP and -2.74 ppm in TPP). Furthermore
      the formation of RhCP and RhTPP complexes is confirmed using CHNS and mass
      spectral analysis; the data are in line with theoretically calculated values. The
      grafting of RhCP and RhTPP on a diamino functionalised SBA-15 support was
      confirmed through low angle XRD, 13C MAS-NMR and SEM-EDAX analysis. Both
      homogeneous and heterogeneous catalysts were utilized for nitrobenzene reduction.
      RhCP and RhTPP heterogenized on SBA-15-F showed complete conversion of
      nitrobenzene with exclusive formation of aniline as a product. The catalytic
      activities were retained in both the systems even after several runs.

PMID- 30118119
TI  - Seawater desalination using pillared graphene as a novel nano-membrane in reverse
      osmosis process: nonequilibrium MD simulation study.
AB  - Herein, the applicability and efficiency of two types of pillared graphene
      nanostructures, namely, (6,6)@G and (7,7)@G, were investigated as membranes in
      reverse osmosis seawater desalination using extensive nonequilibrium molecular
      dynamics simulations. The water permeability for (6,6)@G and (7,7)@G membranes
      was estimated at 4.2 and 6.6 L h-1 cm-2 MPa-1, respectively. According to the
      results, a complete (100%) and pressure-independent salt rejection was estimated
      for both membranes. In addition, the mechanism of seawater desalination through
      the pillared graphene membranes was investigated via the density distribution
      profile of water molecules inside the pillar channels. Furthermore, a series of
      steered MD simulations were performed to construct the potential of mean force
      (PMF) profile of water molecules and salt ions passing through the membranes
      channels. The passing free energy barriers of Na+ and Cl- ions and water
      molecules are 0.86, 0.62, and 0.22 eV, respectively, for the (6,6)@G membrane.
      The corresponding quantities for the (7,7)@G membrane are 0.71, 0.44, and 0.11
      eV, respectively.

PMID- 30118120
TI  - Penta-Pt2N4: an ideal two-dimensional material for nanoelectronics.
AB  - Since the discovery of graphene, two-dimensional (2D) materials have paved new
      ways to design high-performance nanoelectronic devices. To facilitate
      applications of such devices, there are three key requirements that a material
      needs to fulfill: sizeable band gap, high carrier mobility, and robust
      environmental stability. However, among the most popular 2D materials studied in
      recent years, graphene is gapless, hexagonal boron nitride has a very large band
      gap, transition metal dichalcogenides have low carrier mobility, and black
      phosphorene is ambience-sensitive. Thus far, these three characteristics could
      seldom be satisfied by only a single material. Therefore, it is a great challenge
      to find an ideal 2D material that can overcome these limitations. In this study,
      we theoretically predicted a novel planar 2D material penta-Pt2N4, which was
      designed using the Cairo pentagonal tiling as well as the rare nitrogen double
      bonds. Most significantly, 2D penta-Pt2N4 exhibits excellent intrinsic
      properties, including large direct band gap (up to 1.51 eV), high carrier
      mobility (up to 105 cm2.V-1.s-1), very high Young's modulus (up to 0.70 TPa), and
      robust dynamic, thermal, and ambient stabilities. Moreover, penta-Pt2N4 is the
      global minimum structure among 2D materials with PtN2 stoichiometry. We also
      propose a CVD/MBE scheme to enable its experimental synthesis. We envision that
      2D penta-Pt2N4 may find wide applications in the field of nanoelectronics.

PMID- 30118121
TI  - Chemopreventive effects of some popular phytochemicals on human colon cancer: a
      review.
AB  - Colon cancer is one of the major causes of morbidity and mortality worldwide.
      Dietary phytochemicals have been drawing increasing attention for colon cancer
      prevention and treatment due to their chemical diversity, biological activity,
      easy availability, lack of toxic effects, and ability to modulate various signal
      transduction pathways and cell processes. The chemoprotective effects elicited by
      phytochemicals include antioxidative and anti-inflammatory activities, induction
      of phase II enzymes, cell cycle arrest, apoptosis, autophagy, and changes in gut
      microbiota. The present review summarizes the main chemopreventive properties of
      selected phytochemicals (carotenoids, flavonoids, flavonolignan,
      proanthocyanidin, isothiocyanates, terpenoids, peptides, and medicinal plant
      extracts) against colon cancer. It is found that these phytochemicals exhibit
      their anti-colon cancer activity through the modulation of various signaling
      pathways involved in the regulation of chronic inflammation, cell cycle,
      autophagy, apoptosis, metastasis, and angiogenesis. These phytochemicals could be
      helpful starting points in the design and development of novel colon cancer
      chemopreventive agents.

PMID- 30118122
TI  - Ultra-compact branchless plasmonic interferometers.
AB  - Miniaturization of functional optical devices and circuits is a key prerequisite
      for a myriad of applications ranging from biosensing to quantum information
      processing. This development has considerably been spurred by rapid developments
      within plasmonics exploiting its unprecedented ability to squeeze light into
      subwavelength scale. In this study, we investigate on-chip plasmonic systems
      allowing for synchronous excitation of multiple inputs and examine the
      interference between two adjacent excited channels. We present a branchless
      interferometer consisting of two parallel plasmonic waveguides that can be either
      selectively or coherently excited via ultra-compact antenna couplers. The total
      coupling efficiency is quantitatively characterized in a systematic manner and
      shown to exceed 15% for small waveguide separations, with the power distribution
      between the two waveguides being efficiently and dynamically shaped by adjusting
      the incident beam position. The presented design principle can readily be
      extended to other configurations, giving new perspectives for highly dense
      integrated plasmonic circuitry, optoelectronic devices, and sensing applications.

PMID- 30118123
TI  - Kinetic studies of C1 and C2 Criegee intermediates with SO2 using laser flash
      photolysis coupled with photoionization mass spectrometry and time resolved UV
      absorption spectroscopy.
AB  - Recent, direct studies have shown that several reactions of stabilized Criegee
      intermediates (SCI) are significantly faster than indicated by earlier indirect
      measurements. The reaction of SCI with SO2 may contribute to atmospheric sulfate
      production, but there are uncertainties in the mechanism of the reaction of the
      C1 Criegee intermediate, CH2OO, with SO2. The reactions of C1, CH2OO, and C2,
      CH3CHOO, Criegee intermediates with SO2 have been studied by generating
      stabilized Criegee intermediates by laser flash photolysis (LFP) of RI2/O2 (R =
      CH2 or CH3CH) mixtures with the reactions being followed by photoionization mass
      spectrometry (PIMS). PIMS has been used to determine the rate coefficient for the
      reaction of CH3CHI with O2, k = (8.6 +/- 2.2) * 10-12 cm3 molecule-1 s-1 at 295 K
      and 2 Torr (He). The yield of the C2 Criegee intermediate under these conditions
      is 0.86 +/- 0.11. All errors in the abstract are a combination of statistical at
      the 1sigma level and an estimated systematic contribution. For the CH2OO + SO2
      reaction, additional LFP experiments were performed monitoring CH2OO by time
      resolved broadband UV absorption spectroscopy (TRUVAS). The following rate
      coefficients have been determined at room temperature ((295 +/- 2) K):CH2OO +
      SO2: k = (3.74 +/- 0.43) * 10-11 cm3 molecule-1 s-1 (LFP/PIMS),k = (3.87 +/-
      0.45) * 10-11 cm3 molecule-1 s-1 (LFP/TRUVAS)CH3CHOO + SO2: k = (1.7 +/- 0.3) *
      10-11 cm3 molecule-1 s-1 (LFP/PIMS)LFP/PIMS also allows for the direction
      observation of CH3CHO production from the reaction of CH3CHOO with SO2,
      suggesting that SO3 is the co-product. For the reaction of CH2OO with SO2 there
      is no evidence of any variation in reaction mechanism with [SO2] as had been
      suggested in an earlier publication (Chhantyal-Pun et al., Phys. Chem. Chem.
      Phys., 2015, 17, 3617). A mean value of k = (3.76 +/- 0.14) * 10-11 cm3 molecule
      1 s-1 for the CH2OO + SO2 reaction is recommended from this and previous studies.
      The atmospheric implications of the results are briefly discussed.

PMID- 30118124
TI  - Electrochemical methoxymethylation of alcohols - a new, green and safe approach
      for the preparation of MOM ethers and other acetals.
AB  - A new, green, safe, cost-effective and highly efficient electrochemical approach
      for the methoxymethylation of alcohols and phenols was successfully developed.
      The methodology was also applied to the synthesis of substituted acetals.

PMID- 30118125
TI  - Non-covalent interactions for carbonaceous materials: impacts of doping, curving
      and their combination.
AB  - Non-covalent interactions play a critical role during the application of
      carbonaceous materials. DFT calculations are presently employed to study the non
      covalent interactions of graphene flakes (GFs) with ion pairs, considering the
      impacts of doping (electron-deficient and electron-rich) and curving (direction,
      curvature and surface: inner and outer) as well as their combined effects. The
      results are relevant to carbon nanotubes, from which curved graphene sheets can
      be facilely produced. Doping changes the predominant binding configurations and
      fundamentally affects non-covalent interactions, and all dopants enhance the
      binding strength, especially the electron-deficient ones that alter frontier
      orbitals. Curving will not alter the binding configurations but despite the lower
      impact compared to doping, larger curvatures may result in structural collapse.
      The changing trends of non-covalent interactions are opposite for inner and outer
      surfaces. Combined effects during non-covalent interactions are then tackled,
      producing four influencing factors that decrease as identity of dopant >
      curvature > curving direction and identity of dopant > surface. The sign of the
      combined effects (Omega > 0: counteractive while Omega < 0: synergetic) relies
      strongly on the identity of the dopants, and the other factors contribute less as
      elaborated in the text. Meanwhile, insightful clues about utilizing different
      computational methods to handle non-covalent interactions are offered. The
      results obtained thus far greatly further the understanding of non-covalent
      interactions regarding carbonaceous materials.

PMID- 30118126
TI  - High-performance, color-tunable fiber shaped organic light-emitting diodes.
AB  - In recent years, extensive research has been undertaken to develop fiber-shaped
      optoelectronic devices, because they are aesthetically pleasing, light in weight,
      and exhibit superior light emitting properties when compared with conventional
      planar analogues. In this work, we have successfully developed hollow-fiber
      shaped organic light emitting diodes (HF-OLED) with an exceptionally high
      luminance and facile color tunability. The HF-OLED device was fabricated by
      hierarchically depositing amorphous indium-doped tin oxide electrode on a hollow
      fiber, followed by the sequential deposition of light-emitting organic layers and
      Al cathode. The external quantum efficiency of the HF-OLED is more than ~2.0
      times higher than that of a planar-OLED. The experimental results are in good
      agreement with the output of optical simulations, revealing that the use of a
      hollow-fiber has contributed to a ~2.3 times improvement in light extraction
      efficiency. Furthermore, the color emission of a single HF-OLED device could be
      easily tuned from a green to yellowish-green wavelength after the injection of a
      super-yellow solution. The novel color tunable nature of the HF-OLED further
      broadens its application in the field of modern lighting and display technology.

PMID- 30118127
TI  - Size-controlled electron transfer rates determine hydrogen generation efficiency
      in colloidal Pt-decorated CdS quantum dots.
AB  - Semiconducting quantum dots (QDs) have been considered as promising building
      blocks of solar energy harvesting systems because of size-dependent electronic
      structures, e.g. QD-metal heterostructures for solar-driven H2 production. In
      order to design improved systems, it is crucial to understand size-dependent QD
      metal interfacial electron transfer dynamics, picosecond processes in particular.
      Here, we report that the transfer rates of photogenerated electrons in Pt
      decorated CdS QDs can be varied over more than two orders of magnitude by
      controlling the QD size. In small QDs (2.8 nm diameter), conduction band
      electrons transfer to Pt sites in an average timescale of ~30 ps, giving a
      transfer rate of 2.9 * 1010 s-1 while in significantly larger particles (4.8 nm
      diameter) the transfer rates decrease to 1.4 * 108 s-1. We attribute this to the
      tuning of the electron transfer driving force via the quantum confinement
      controlled energetic off-set between the involved electronic states of the QDs
      and the co-catalyst. The same size-dependent trend is observed in the presence of
      an electron acceptor in solution. With methyl viologen present, electrons leave
      the QDs within 1 ps for 2.8 nm QDs while for 4.6 nm QDs this process takes nearly
      40 ps. The transfer rates are directly correlated with H2 generation
      efficiencies: faster electron transfer leads to higher H2 generation
      efficiencies. 2.8 nm QDs display a H2 generation quantum efficiency of 17.3%,
      much higher than the 11.4% for their 4.6 nm diameter counterpart. We explain
      these differences by the fact that slower electron transfer cannot compete as
      efficiently as faster electron transfer with recombination and other losses.

PMID- 30118128
TI  - Detecting miRNA biomarkers from extracellular vesicles for cardiovascular disease
      with a microfluidic system.
AB  - According to World Health Organization reports, cardiovascular diseases (CVDs)
      are amongst the major causes of death globally and are responsible for over 18
      million deaths every year. Traditional detection methods for CVDs include cardiac
      computerized tomography scans, electrocardiography, and myocardial perfusion
      imaging scans. Although diagnosis of CVDs through such bio-imaging techniques is
      common, these methods are relatively costly and cannot detect CVDs in their
      earliest stages. In contrast, the levels of certain micro RNA (miRNA) biomarkers
      extracted from extracellular vesicles (EVs) in the bloodstream have been
      recognized as promising indicators for early CVD detection. However, detection
      and quantification of miRNA using existing methods are relatively labor-intensive
      and time-consuming. In this study, a new integrated microfluidic system equipped
      with highly sensitive field-effect transistors (FETs) was capable of performing
      EV extraction, EV lysis, target miRNA isolation and miRNA detection within 5 h.
      The limit of detection was within the physiological range (femtomolar) for two
      targeted miRNAs, miR-21 and miR-126, meaning that this integrated microfluidic
      system has the potential to be used as a tool for early detection of CVDs.

PMID- 30118129
TI  - Inorganic salt transition states: a stable and highly stretchable elastomer-like
      phase (ELP) of phosphate salts at the air-solid interface.
AB  - An elastomer-like phase (ELP) of phosphate salts with ultra-high stability was
      successfully prepared at the air-solid interface. ELPs possess multilayered
      structures, and exhibit high elasticity, and strong self-healing abilities. These
      unique properties of ELPs greatly expand our understanding of inorganic salts and
      reveal their potential application in future material fields.

PMID- 30118130
TI  - Tellurene: its physical properties, scalable nanomanufacturing, and device
      applications.
AB  - Tellurium (Te) has a trigonal crystal lattice with inherent structural
      anisotropy. Te is multifunctional, e.g., semiconducting, photoconductive,
      thermoelectric, piezoelectric, etc., for applications in electronics, sensors,
      optoelectronics, and energy devices. Due to the inherent structural anisotropy,
      previously reported synthetic methods predominantly yield one-dimensional (1D) Te
      nanostructures. Much less is known about 2D Te nanostructures, their processing
      schemes, and their material properties. This review focuses on the synthesis and
      morphology control of emerging 2D tellurene and summarizes the latest
      developments in understanding the fundamental properties of monolayer and few
      layer tellurene, as well as the recent advances in demonstrating prototypical
      tellurene devices. Finally, the prospects for future research and application
      opportunities as well as the accompanying challenges of 2D tellurene are
      summarized and highlighted.

PMID- 30118131
TI  - Diffusion controlled multilayer electrocatalysts via graphene oxide nanosheets of
      varying sizes.
AB  - Controlling the architecture of hybrid nanomaterial electrodes is critical for
      understanding their fundamental electrochemical mechanisms and applying these
      materials in future energy conversion and storage systems. Herein, we report
      highly tunable electrocatalytic multilayer electrodes, composed of palladium
      nanoparticles (Pd NPs) supported by graphene sheets of varying lateral sizes,
      employing a versatile layer-by-layer (LbL) assembly method. We demonstrate that
      the electrocatalytic activity is highly tunable through the control of the
      diffusion and electron pathways within the 3-dimensional multilayer electrodes. A
      larger-sized-graphene-supported electrode exhibited its maximum performance with
      a thinner film, due to facile charge transfer by the mass transfer limited in the
      early stage, while a smaller-sized-graphene-supported electrode exhibited its
      highest current density with higher mass loading in the thicker films by enabling
      facile mass transfer through increased diffusion pathways. These findings of the
      tortuous-path effect on the electrocatalytic electrode supported by varying sized
      graphene provide new insights and a novel design principle into electrode
      engineering that will be beneficial for the development of effective
      electrocatalysts.

PMID- 30118132
TI  - Enhancement of the guest orderliness in a low-symmetric perovskite-type metal
      organic framework influenced by Jahn-Teller distortion.
AB  - Copper guanidinium formate (CuGF) is an ABX3-type metal-organic framework bearing
      a polar space group, housing a guest-host connectivity between the guanidinium
      and formate ions. With the maiden data-set based on single-crystal neutron
      diffraction, we report the discovery of the guest orderliness which surprisingly
      accommodates an enhancement for low-symmetric CuGF, while the scenario is
      contrasting for the high-symmetric Mn cousin. We provide an in-depth evaluation
      of the inter-guanidinium scheme and thus propose the mechanism behind this
      unusual effect.

PMID- 30118134
TI  - Electron-withdrawing effects on the molecular structure of 2- and 3
      nitrobenzonitrile revealed by broadband rotational spectroscopy and their
      comparison with 4-nitrobenzonitrile.
AB  - The rotational spectra of 2- and 3-nitrobenzonitrile were recorded via chirped
      pulse Fourier transform microwave spectroscopy in the frequency range of 2-8 GHz.
      These molecules each display large dipole moments, making them viable candidates
      for deceleration and trapping experiments with AC-electric fields. For both
      molecules, the main isotopologues and all isotopologues of the respective 13C-,
      15N-, 18O-monosubstituted species in their natural abundance were assigned. These
      assignments allowed for the structural determination of 2- and 3
      nitrobenzonitrile via Kraitchman's equations as well as a mass-dependent least
      squares fitting approach. The experimentally determined structural parameters are
      then compared to those obtained from quantum-chemical calculations for these two
      molecules and 4-nitrobenzonitrile. Structural changes caused by steric
      interaction and competition for the electron density of the phenyl ring highlight
      how these strong electron-withdrawing substituents affect one another according
      to their respective positions on the phenyl ring.

PMID- 30118133
TI  - Modular bimetallic complexes with a sulfonamido-based ligand.
AB  - A series of bimetallic complexes prepared with the ligands N,N,N',N'
      tetramethylethane-1,2-diamine (TMEDA) and N,N',N''-[2,2',2''-nitrilotris(ethane
      2,1-diyl)]tris(2,4,6-trimethylbenzenesulfonamido) ([MST]3-) is described. Four
      diiron compounds of the formulation (TMEDA)FeII(X)-(MU-OH)-FeIIIMST were
      prepared, in which the X- ligands are the anions OTf-, Br-, SCN-, or N3-.
      Additionally, two heterobimetallic compounds of the formulation (TMEDA)MII(OTf)
      (MU-OH)-FeIIIMST (MII = CoII or NiII) were synthesized. All these compounds have
      similar spectroscopic and structural properties. The diiron compounds exhibit
      perpendicular-mode electron paramagnetic resonance spectra consistent with S =
      1/2 spin ground states, which is expected for high-spin FeII and FeIII centres
      that are antiferromagnetically coupled. The heterobimetallic (TMEDA)NiII(OTf)-(MU
      OH)-FeIIIMST complex had a spin state of S = 3/2 that also resulted from
      antiferromagnetic coupling between the high-spin NiII and FeIII centres. The
      modularity of this system is further demonstrated by the substitution of the
      TMEDA ligand with ethylenediamine (en); for this species two equivalents of en
      coordinate to the FeII centre to form [(en)2FeII-(MU-OH)-FeIIIMST]OTf. These
      results demonstrate that a modular bimetallic system has been developed in which
      the key components can be modified.

PMID- 30118135
TI  - Energy transfer between Eu3+ and Nd3+ in near-infrared emitting beta-triketonate
      coordination polymers.
AB  - Isomorphous beta-triketonate-based lanthanoid polymers containing tris(4
      methylbenzoyl)methanide (mtbm) and Rb+ with formula {[Ln(Rb)(mtbm)4]2}n (Ln =
      Eu3+ and Nd3+) have been synthesised and structurally characterised. The
      photophysical properties for the Nd3+ complex presented relatively long lifetimes
      and high quantum yields in comparison with analogous beta-diketonate complexes.
      Mixed lanthanoid complexes were also formed and their luminescence properties
      studied, with effective sensitisation of the 4F3/2 of Nd3+via the 5D0 of Eu3+,
      which is to the best of our knowledge the first example of Eu3+ to Nd3+
      sensitisation in a structurally defined coordination complex or polymer.

PMID- 30118136
TI  - Shaping efficiency as a function of time of a new heat-treated instrument.
AB  - AIM: To assess the shaping ability of the new XP-endo Shaper instrument after
      different working times. METHODOLOGY: Ten mesial roots of mandibular molars were
      scanned in a micro-computed tomographic device and prepared using the XP-endo
      Shaper instrument up to the working length (WL) according to the manufacturer's
      recommendation. Then, each specimen was subjected to an extra 15, 30 and 45 s of
      active instrumentation at the WL. Postoperative scans were performed after canal
      preparation at each time-point. Then, the registered pre- and postoperative
      datasets were examined to evaluate the percentages of volume and surface area of
      the instrumented canal, surface area of noninstrumented canal areas and the
      volume of removed dentine. Repeated measures general linear model was used to
      compare the differences in either the increase or the reduction of the parameters
      amongst the time-points. Alpha-error was set at 5%. RESULTS: Extending the period
      of XP-endo Shaper active instrumentation at WL significantly influenced several
      parameters such as volume (P < 0.001) and surface area (P < 0.001) of the
      instrumented canal, surface area of noninstrumented canal areas (P < 0.001), and
      volume of removed dentine (P < 0.001). CONCLUSIONS: Extending the activation time
      of XP-endo Shaper instruments at WL resulted in a more comprehensive root canal
      preparation, increasing the volume and surface area of root canal preparation and
      the volume of removed dentine.

PMID- 30118137
TI  - Subungual exostosis with postoperative recurrence followed by spontaneous
      regression.

PMID- 30118138
TI  - Health in All local Policies: Lessons learned on intersectoral collaboration in a
      community-based health promotion network in Denmark.
AB  - Health promotion increasingly involves collaboration with civil society
      organisations and the private sector rather than being implemented exclusively by
      public sector stakeholders. Health in All Policies (HiAP) is an approach that
      promotes health in policy-making across public sectors. This study explored
      intersectoral integration and collaboration for health promotion at a local
      community level through a qualitative single case study of a local community
      network in Denmark: the Husum Health Network. The paper describes and discusses
      strengths, weaknesses, and challenges of HiAP-inspired local efforts to build
      alliances and supportive environments for health within an inter-organisational
      community-based network. The data were generated from participant observations
      made at 11 meetings and events organised by the network partners and nine
      qualitative, semi-structured interviews with Husum Health Network partners
      conducted from August 2014 to February 2015. The data were analysed using a
      theoretical framework introduced by Axelsson and Axelsson (2006) to characterise
      aspects of integration and differentiation between organisations. With high
      levels of structural and functional differentiation between the partners, the
      network provided an opportunity to exercise inter-organisational integration at
      the local level. Integration was fostered by knowledge sharing, face-to-face
      interaction, and communal events. However, the loose structure of the network was
      a challenge to its sustainability and achievement. We argue that Health in All
      local Policies is a meaningful concept in the context of local community
      development only when referring to the polices and strategies of all stakeholder
      organisations involved in decision-making and agenda setting, and not just local
      government institutions.

PMID- 30118139
TI  - Characterization of three strains of Capnocytophaga canis isolated from patients
      with sepsis.
AB  - Capnocytophaga canimorsus and Capnocytophaga cynodegmi, both commensal bacteria
      in the oral cavities of dogs and cats, are zoonotic pathogens. In particular, C.
      canimorsus causes sepsis and fatal septic shock. Recently, a novel Capnocytophaga
      species, C. canis, was isolated from the oral cavities of healthy dogs. It is
      reportedly oxidase-negative and therefore considered avirulent in humans. In the
      present study, three strains of C. canis were isolated from Japanese patients
      with sepsis. All three strains, HP20001, HP33001 and HP40001, were oxidase
      positive. Nucleotide sequence identities of the 16S rRNA gene of the three
      strains to the C. canimorsus type strain ATCC35979, C. cynodegmi type strain
      ATCC49044 and C. canis type strain LMG29146 were 96.9-97.0%, 96.9-97.0% and 99.7
      99.8%, respectively. Multi-locus sequence analysis based on seven house-keeping
      genes, dnaJ, fumC, glyA, gyrB, murG, trpB and tuf, revealed that the oxidase
      positive C. canis strains isolated in Japan and oxidase-negative strains of C.
      canis from canine oral cavities in Switzerland were clustered in different
      genetic subgroups. These results indicate that the virulence of C. canis strains
      in humans is associated with oxidase activity.

PMID- 30118140
TI  - Geometry optimization of electrically floating PET inserts for improved RF
      penetration for a 3 T MRI system.
AB  - PURPOSE: An electrically floating radio frequency (RF) shielded PET insert with
      individual PET detectors shielded by separate Faraday cages enables the MRI built
      in body RF coil to be used at least as an RF transmitter, in which the RF field
      penetrates the imaging region inside the PET ring through the narrow gaps between
      the shielded PET detector modules. Because the shielded PET ring blocks more than
      90% of the imaging region for the transmit field from the body RF coil, it is
      very challenging to obtain the required RF field inside a full-ring floating PET
      insert. In this study, experiments were performed on the dependence of RF
      penetrability on different geometric aspects of the shielded PET modules and PET
      rings to optimize the design parameters to obtain the required RF field inside
      the PET ring. METHODS: We developed several prototype cylindrical full-ring PET
      inserts using completely enclosed empty RF shield boxes (considered as dummy PET
      modules). Considering the RF shield box, we conducted studies for different axial
      lengths (240 and 120 mm) and heights (30 and 45 mm) of the shield boxes. On the
      other hand, considering the PET ring geometry, we also performed studies on three
      different categories of PET rings: a long-ring insert (longer than the MRI
      phantom), a short-ring insert (shorter than the MRI phantom), and a two-ring
      insert that combined two short-rings. In each ring category, two different inter
      shield box gaps (1 and 3 mm) were considered. In the case of the two-ring insert,
      three different ring-gaps (5, 10, and 20 mm) were studied. In total, 21 PET
      inserts were studied with an inner diameter (i.d.) of 210 mm. To study the effect
      of ring diameter, another long-ring insert was studied for the 270 mm i.d.
      Experiments were conducted for the transmit RF (B1 ) fields and signal-to-noise
      ratios of spin-echo and gradient-echo images using a homogeneous phantom in a 700
      mm bore-diameter 3 T clinical MRI system. RF pulse amplitudes generated
      automatically by the MRI system were recorded for comparison. RESULTS: A PET
      insert with a 3 mm inter-box gap was found to perform the best, at a level which
      is acceptable for PET imaging. In the case of an insert of multiple short-rings
      instead of one long-ring insert, the 5 and 10 mm ring-gaps provided higher RF
      field penetration. Increasing the inter-box gap improved the RF field
      penetration, whereas a ring-gap that was too wide concentrated the field near the
      ring-gap region. Relatively reduced RF power was required for wider inter-box gap
      or ring-gap or larger shield box height. Moreover, the rectangular shield box
      outperformed the trapezoidal shield box. On the other hand, when we changed the
      inner or outer diameter of the PET ring by keeping the same transaxial width of
      the shield boxes, we did not see any noticeable variation. CONCLUSIONS: Our study
      results provide comprehensive guidance on the geometrical design aspects of RF
      penetrable PET inserts for efficient RF penetration inside the PET ring. By
      choosing proper geometric design parameters, we could get the RF field that was
      similar to the MRI-only case.

PMID- 30118141
TI  - Development of Kasabach-Merritt phenomenon following vaccination: More than a
      coincidence?
AB  - Kasabach-Merritt phenomenon (KMP) occurred uniquely in patients with kaposiform
      hemangioendothelioma (KHE) and tufted angioma (TA). We report the clinical
      characteristics of two patients with KHE involving the right upper arm. The
      patients demonstrated rapid enlargement of the lesion with severe KMP shortly
      after vaccination. Sirolimus was used to treat the KHE with KMP. The patients
      showed a quick normalization of the platelet level. The follow-up examination
      revealed that the size of the mass was significantly decreased. This report
      raises the intriguing possibility that extrinsic factors may contribute to the
      development of KMP in the context of an already existing KHE.

PMID- 30118142
TI  - Lower Prefrontal and Hippocampal Volume and Diffusion Tensor Imaging Differences
      Reflect Structural and Functional Abnormalities in Abstinent Individuals with
      Alcohol Use Disorder.
AB  - BACKGROUND: Alcohol use disorder (AUD) is known to have adverse effects on brain
      structure and function. Multimodal assessments investigating volumetric,
      diffusion, and cognitive characteristics may facilitate understanding of the
      consequences of long-term alcohol use on brain circuitry, their structural
      impairment patterns, and their impact on cognitive function in AUD. METHODS:
      Voxel- and surface-based volumetric estimations, diffusion tensor imaging (DTI),
      and neuropsychological tests were performed on 60 individuals: 30 abstinent
      individuals with AUD (DSM-IV) and 30 healthy controls. Group differences in the
      volumes of cortical and subcortical regions, fractional anisotropy (FA), axial
      and radial diffusivities (AD and RD, respectively), and performance on
      neuropsychological tests were analyzed, and the relationship among significantly
      different measures was assessed using canonical correlation. RESULTS: AUD
      participants had significantly smaller volumes in left pars orbitalis, right
      medial orbitofrontal, right caudal middle frontal, and bilateral hippocampal
      regions, lower FA in 9 white matter (WM) regions, and higher FA in left thalamus,
      compared to controls. In AUD, lower FA in 6 of 9 WM regions was due to higher RD
      and due to lower AD in the left external capsule. AUD participants scored lower
      on problem-solving ability, visuospatial memory span, and working memory.
      Positive correlations of prefrontal cortical, left hippocampal volumes, and FA in
      4 WM regions with visuospatial memory performance and negative correlation with
      lower problem-solving ability were observed. Significant positive correlation
      between age and FA was observed in bilateral putamen. CONCLUSIONS: Findings
      showed specific structural brain abnormalities to be associated with visuospatial
      memory and problem-solving ability-related impairments observed in AUD. Higher RD
      in 6 WM regions suggests demyelination, and lower AD in left external capsule
      suggests axonal loss in AUD. The positive correlation between FA and age in
      bilateral putamen may reflect accumulation of iron depositions with increasing
      age.

PMID- 30118143
TI  - Estimating lung, breast, and effective dose from low-dose lung cancer screening
      CT exams with tube current modulation across a range of patient sizes.
AB  - PURPOSE: The purpose of this study was to estimate the radiation dose to the lung
      and breast as well as the effective dose from tube current modulated (TCM) lung
      cancer screening (LCS) scans across a range of patient sizes. METHODS: Monte
      Carlo (MC) methods were used to calculate lung, breast, and effective doses from
      a low-dose LCS protocol for a 64-slice CT that used TCM. Scanning parameters were
      from the protocols published by AAPM's Alliance for Quality CT. To determine
      lung, breast, and effective doses from lung cancer screening, eight GSF/ICRP
      voxelized phantom models with all radiosensitive organs identified were used to
      estimate lung, breast, and effective doses. Additionally, to extend the limited
      size range provided by the GSF/ICRP phantom models, 30 voxelized patient models
      of thoracic anatomy were generated from LCS patient data. For these patient
      models, lung and breast were semi-automatically segmented. TCM schemes for each
      of the GSF/ICRP phantom models were generated using a validated method wherein
      tissue attenuation and scanner limitations were used to determine the TCM output
      as a function of table position and source angle. TCM schemes for voxelized
      patient models were extracted from the raw projection data. The water equivalent
      diameter, Dw, was used as the patient size descriptor. Dw was estimated for the
      GSF/ICRP models. For the thoracic patient models, Dw was extracted from the DICOM
      header of the CT localizer radiograph. MC simulations were performed using the
      TCM scheme for each model. Absolute organ doses were tallied and effective doses
      were calculated using ICRP 103 tissue weighting factors for the GSF/ICRP models.
      Metrics of scanner radiation output were determined based on each model's TCM
      scheme, including CTDIvol , dose length product (DLP), and CTDIvol, Low Att , a
      previously described regional metric of scanner output covering most of the lungs
      and breast. All lung and breast doses values were normalized by scan-specific
      CTDIvol and CTDIvol, Low Att . Effective doses were normalized by scan-specific
      CTDIvol and DLP. Absolute and normalized doses were reported as a function of Dw.
      RESULTS: Lung doses normalized by CTDIvol, Low Att were modeled as an exponential
      relationship with respect to Dw with coefficients of determination (R2 ) of 0.80.
      Breast dose normalized by CTDIvol, Low Att was modeled with an exponential
      relationship to Dw with an R2 of 0.23. For all eight GSF/ICRP phantom models, the
      effective dose using TCM protocols was below 1.6 mSv. Effective doses showed some
      size dependence but when normalized by DLP demonstrated a constant behavior.
      CONCLUSION: Lung, breast, and effective doses from LCS CT exams with TCM were
      estimated with respect to patient size. Normalized lung dose can be reasonably
      estimated with a measure of a patient size such as Dw and regional metric of
      CTDIvol covering the thorax such as CTDIvol, Low Att , while normalized breast
      dose can also be estimated with a regional metric of CTDIvol but with a larger
      degree of variability than observed for lung. Effective dose normalized by DLP
      can be estimated with a constant multiplier.

PMID- 30118144
TI  - Kilovoltage transit and exit dosimetry for a small animal image-guided
      radiotherapy system using built-in EPID.
AB  - PURPOSE: We investigated the potential use of the built-in electronic portal
      imaging device (EPID) in the small animal radiation research platform (SARRP) as
      a dosimeter in the kV energy range. To this end, we developed a method for
      converting portal images to a two-dimensional (2D) dose maps at the detector
      plane and object's exit surface and validated them against empirical dose
      measurements. METHODS: We calibrated the SARRP's EPID to measure transit dose.
      The transit dose map was back-projected to calculate 2D dose distribution at the
      object's exit surface. The accuracy of transit and exit dose distributions was
      independently validated with a PinPoint ion chamber (IC) and Gafchromic EBT3 film
      measurements for a range of radiation dose rates (0.43-2.78 cGy/s), cone sizes (5
      40 mm), in a homogeneous phantom of varying thickness (0-50 mm) and in an
      inhomogeneous phantom containing graphite, cork, air, and aluminum. RESULTS: In
      air central axis (CAX) transit dose values measured with the EPID showed close
      agreement with film and IC measurements. The maximum differences in EPID in-air
      transit measurements with film or IC measurements were 1%. The EPID was capable
      of accurately measuring phantom transit dose independently of the attenuating
      phantom thickness, with average discrepancies of 0.5% and 2.9% with IC and film,
      respectively, where the maximum difference between the EPID and the IC was 1.8%.
      The results were slightly worse for film, with maximum differences in 4.9%.
      Output factor measurements using EPID were within 2.9% of both IC and film
      measurements. In addition, calculated exit doses agreed with film values within
      <=3.1%, for attenuating phantom thicknesses >=15 mm. The agreement became worse
      with decreasing phantom thickness; for thicknesses of 10 and 5 mm, agreements
      were <=5.7% and <=6.9%, respectively. Compared to film, transit and exit profiles
      measured with the EPID showed average differences <2% for both homogeneous and
      inhomogeneous materials. CONCLUSION: We developed and validated a novel 2D
      transit/exit dosimetry for a kV SA-IGRT system using an EPID. We verified the
      accuracy of our method to measure EPID transit and exit dose distributions for a
      range of dose rates, beam attenuation, and collimation. Our results indicate that
      the EPID can be used as a simple, convenient device for kV dose delivery
      verification in small animal radiotherapy.

PMID- 30118145
TI  - Intestinal epithelial cells and T cells differentially recognize and respond to
      Candida albicans yeast and hypha.
AB  - Inflammatory bowel diseases (IBD) are a multifactorial disorder. Our
      understanding of the role of bacteria in the pathogenesis of IBD has increased
      substantially; however, only scarce data exist regarding the role of commensal
      fungi in maintaining intestinal homeostasis and triggering IBD. Candida albicans
      (C. albicans) is a member of the intestinal mycobiome and proposed to contribute
      to IBD pathogenesis. We aimed to investigate the influence of the two
      morphologies of C. albicans, yeast and hypha, on epithelial cells and T cells
      from IBD patients versus healthy controls. We found that C. albicans was
      recognized by both epithelial cells lines and T cells. In the intestinal
      epithelial cell line, Caco-2, response to hypha was different than to yeast
      cells, and this was mimicked by synthetic beta-glucans and Pam3CSK4. Unstimulated
      T cells exhibited increased activation and pro-inflammatory cytokine secretion
      upon exposure, while there was no effect on apoptosis or proliferation. In
      contrast, C. albicans-challenged CD3-stimulated T-cells exhibited decreased
      activation, cytokine secretion, apoptosis, and proliferation, suggesting
      reciprocal responsiveness to C. albicans. Glycans alone did not mimic
      abovementioned influences on T cells, suggesting alternative modes of
      recognition. In conclusion, we provide evidence for glycan dependent and
      independent recognition of C. albicans by epithelial cells and T cells.

PMID- 30118146
TI  - Reciprocal relationship between herpes zoster and cardiovascular diseases: A
      nationwide population-based case-control study in Korea.
AB  - Recently, herpes zoster (HZ) has been identified as a risk factor for stroke, but
      there have been few studies on the relationship between HZ and other
      cardiovascular diseases (CVD), including myocardial infarction (MI) and heart
      failure (HF). The purpose of this study was to investigate the risk of HZ
      occurrence after CVD and the occurrence of CVD after HZ. This was a retrospective
      case-control study based on the National Health Insurance System claims database
      for 20 311 patients with HZ and 13 980 patients with CVD and 1:5 age- and sex
      matched control subjects for each from January 2006 to December 2013. We
      evaluated the reciprocal relationship between HZ and CVD including MI, ischemic
      stroke and HF. Severe HZ requiring hospitalization independently increased the
      risk of subsequent MI (hazard ratio [HR], 1.831; 95% confidence interval [CI],
      1.354-2.476)], ischemic stroke (HR, 1.523; 95% CI, 1.212-1.915) and HF (HR,
      2.034; 95% CI, 1.615-2.562) during the study period. Likewise, patients with an
      episode of MI, ischemic stroke or HF were also at increased risk of HZ
      hospitalization (after MI: HR, 1.625; 95% CI, 1.144-2.308; after stroke: HR,
      1.518; 95% CI, 1.177-1.957; and after HF: HR, 1.485, 95% CI 1.041-2.117). Our
      results suggest that there is a significant reciprocal relationship between
      severe HZ requiring hospitalization and CVD including MI, ischemic stroke and HF.

PMID- 30118147
TI  - Biochemical and physiological characterization of a halotolerant Dunaliella
      salina isolated from hypersaline Sambhar Lake, India.
AB  - The objective of the present study was to characterize intrinsic physiological
      and biochemical properties of the wall-less unicellular cholorophyte Dunaliella
      salina isolated from a hypersaline Sambhar Lake. The strain grew optimally at 0.5
      M NaCl and 16:8 h L:D photoperiod along with maintaining low level of
      intracellular Na+ even at higher salinity, emphasizing special features of its
      cell membranes. It was observed that the cells experienced stress beyond 2 M NaCl
      as evidenced by increased intracellular reactive oxygen species and antioxidative
      enzymes, nevertheless proline and malondialdehyde content declined sharply
      accompanied by higher neutral lipid accumulation. Salinity exceeding 2 M resulted
      decrease in photosynthetic quantum yield (Fv/Fm) and enhanced glycerol synthesis
      accompanied by leakage. Super oxide dismutase seemed to play a pivotal role in
      antioxidative defense as eight isoforms were expressed differentially while
      catalase and glutathione peroxidase showing no significant change in their
      expression at higher salinity. The ability of D. salina to grow in range of
      salinities by sustaining healthy photosynthetic apparatus along with accumulation
      of valuable products made this alga an ideal organism that can be exploited as
      resource for biofuel and commercial products.

PMID- 30118148
TI  - Passive heat therapy protects against endothelial cell hypoxia-reoxygenation via
      effects of elevations in temperature and circulating factors.
AB  - KEY POINTS: Accumulating evidence indicates that passive heat therapy (chronic
      use of hot tubs or saunas) has widespread physiological benefits, including
      enhanced resistance against novel stressors ('stress resistance'). Using a cell
      culture model to isolate the key stimuli that are likely to underlie
      physiological adaptation with heat therapy, we showed that both mild elevations
      in temperature (to 39 degrees C) and exposure to serum from human subjects who
      have undergone 8 weeks of heat therapy (i.e. altered circulating factors)
      independently prevented oxidative and inflammatory stress associated with hypoxia
      reoxygenation in cultured endothelial cells. Our results elucidate some of the
      mechanisms (i.e. direct effects of temperature vs. circulating factors) by which
      heat therapy seems to improve resistance against oxidative and inflammatory
      stress. Heat therapy may be a promising intervention for reducing cellular damage
      following ischaemic events, which has broad implications for patients with
      cardiovascular diseases and conditions characterized by 'chronic' ischaemia (e.g.
      peripheral artery disease, metabolic diseases, obesity). ABSTRACT: Repeated
      exposure to passive heat stress ('heat therapy') has widespread physiological
      benefits, including cellular protection against novel stressors. Increased heat
      shock protein (HSP) expression and upregulation of circulating factors may impart
      this protection. We tested the isolated abilities of mild heat pretreatment and
      serum from human subjects (n = 10) who had undergone 8 weeks of heat therapy to
      protect against cellular stress following hypoxia-reoxygenation (H/R), a model of
      ischaemic cardiovascular events. Cultured human umbilical vein endothelial cells
      were incubated for 24 h at 37 degrees C (control), 39 degrees C (heat
      pretreatment) or 37 degrees C with 10% serum collected before and after 8 weeks
      of passive heat therapy (four to five times per week to increase rectal
      temperature to >= 38.5 degrees C for 60 min). Cells were then collected before
      and after incubation at 1% O2 for 16 h (hypoxia; 37 degrees C), followed by 20%
      O2 for 4 h (reoxygenation; 37 degrees C) and assessed for markers of cell stress.
      In control cells, H/R increased nuclear NF-kappaB p65 protein (i.e. activation)
      by 106 +/- 38%, increased IL-6 release by 37 +/- 8% and increased superoxide
      production by 272 +/- 45%. Both heat pretreatment and exposure to heat therapy
      serum prevented H/R-induced NF-kappaB activation and attenuated superoxide
      production; by contrast, only exposure to serum attenuated IL-6 release. H/R also
      decreased cytoplasmic haemeoxygenase-1 (HO-1) protein (known to suppress NF
      kappaB), in control cells (-25 +/- 8%), whereas HO-1 protein increased following
      H/R in cells pretreated with heat or serum-exposed, providing a possible
      mechanism of protection against H/R. These data indicate heat therapy is capable
      of imparting resistance against inflammatory and oxidative stress via direct heat
      and humoral factors.

PMID- 30118149
TI  - Automation of the in vitro micronucleus assay using the Imagestream(r) imaging
      flow cytometer.
AB  - The in vitro micronucleus (MN) assay is a well-established test for evaluating
      genotoxicity and cytotoxicity. The use of manual microscopy to perform the assay
      can be laborious and often suffers from user subjectivity and interscorer
      variability. Automated methods including slide-scanning microscopy and
      conventional flow cytometry have been developed to eliminate scorer bias and
      improve throughput. However, these methods possess several limitations such as
      lack of cytoplasmic visualization using slide-scanning microscopy and the
      inability to visually confirm the legitimacy of MN or storage of image data for
      re-evaluation using flow cytometry. The ImageStreamX(r) MK II (ISX) imaging flow
      cytometer has been demonstrated to overcome all of these limitations. The ISX
      combines the speed, statistical robustness, and rare event capture capability of
      conventional flow cytometry with high resolution fluorescent imagery of
      microscopy and possesses the ability to store all collected image data. This
      paper details the methodology developed to perform the in vitro MN assay in human
      lymphoblastoid TK6 cells on the ISX. High resolution images of micronucleated
      mono- and bi-nucleated cells as well as polynucleated cells can be acquired at a
      high rate of capture. All images can then be automatically identified,
      categorized and enumerated in the data analysis software that accompanies the
      ImageStream, allowing for the scoring of both genotoxicity and cytotoxicity. The
      results demonstrate that statistically significant increases in MN frequency when
      compared with solvent controls can be detected at varying levels of cytotoxicity
      following exposure to well-known aneugens and clastogens. This work demonstrates
      a fully automated method for performing the in vitro micronucleus assay on the
      ISX imaging flow cytometry platform. (c) 2018 The Author. Cytometry Part A
      published by Wiley Periodicals, Inc. on behalf of ISAC.

PMID- 30118151
TI  - Mixed Hepatocellular-Cholangiocarcinoma: Is It Time to Rethink Consideration for
      Liver Transplantation?

PMID- 30118150
TI  - Mucopolysaccharidosis type VI (MPS VI) and molecular analysis: Review and
      classification of published variants in the ARSB gene.
AB  - Maroteaux-Lamy syndrome (MPS VI) is an autosomal recessive lysosomal storage
      disorder caused by pathogenic ARSB gene variants, commonly diagnosed through
      clinical findings and deficiency of the arylsulfatase B (ASB) enzyme. Detection
      of ARSB pathogenic variants can independently confirm diagnosis and render
      genetic counseling possible. In this review, we collect and summarize 908 alleles
      (201 distinct variants, including 3 polymorphisms previously considered as
      disease-causing variants) from 478 individuals diagnosed with MPS VI, identified
      from literature and public databases. Each variant is further analyzed for
      clinical classification according to American College of Medical Genetics and
      Genomics (ACMG) guidelines. Results highlight the heterogeneity of ARSB alleles,
      with most unique variants (59.5%) identified as missense and 31.7% of unique
      alleles appearing once. Only 18% of distinct variants were previously recorded in
      public databases with supporting evidence and clinical significance. ACMG
      recommends publishing clinical and biochemical data that accurately characterize
      pathogenicity of new variants in association with reporting specific alleles.
      Variants analyzed were sent to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/),
      and MPS VI locus-specific database (http://mps6-database.org) where they will be
      available. High clinical suspicion coupled with diagnostic testing for deficient
      ASB activity and timely submission and classification of ARSB variants with
      biochemical and clinical data in public databases is essential for timely
      diagnosis of MPS VI.

PMID- 30118152
TI  - Synthesis and Properties of Networks Based on Thiol-ene Chemistry Using a CO2 
      Based delta-Lactone.
AB  - 3-Ethylidene-6-vinyltetrahydro-2H-pyran-2-one, a divinyl delta-lactone derived
      from CO2 and 1,3-butadiene, is used for the synthesis of networks with various
      compositions through the thiol-ene click reaction with di- and tri-thiol
      compounds. Thermal, mechanical, and optical properties of the networks are
      characterized. The networks have sharp and uniform glass transitions and show
      good thermal stability with T d from 287 to 332  degrees C. Mechanical properties
      of the networks can be adjusted by the cross-link density; 6.18 MPa of tensile
      strength, 574% break elongation and 1.84 of tan delta at maximum are reached.
      Metal complexation makes the networks tougher due to additional cross-links. The
      highly homogeneous networks are transparent with average 90% transmittance of
      visible light, and of decent refractive indices around 1.55. Swelling-induced
      twist shape transformation and visible QR code under UV light is realized by
      pattern of the network.

PMID- 30118153
TI  - Risk of Contraceptive Lapse and New Sexual Partnership Among Female University
      Students Traveling Internationally.
AB  - CONTEXT: International travel is common and may influence women's sexual and
      reproductive health through myriad pathways. Existing studies focus on travelers'
      risk of acquiring STDs, but not their pregnancy prevention behaviors. Further, it
      is unclear whether sexual and reproductive health outcomes observed for female
      travelers are associated with travel itself, because few studies compare
      travelers with nontravelers. METHODS: An online survey was conducted in 2016-2017
      among females attending a U.S. university who reported a history of sex with men;
      the sample comprised 340 students who had traveled internationally in the past
      three months (travelers) and 170 who intended to travel in the next three months
      (pretravelers). Multivariable modified Poisson regression models assessed
      associations between travel status and two outcomes during travelers' recent trip
      or a period of similar duration for pretravelers: contraceptive lapse (incorrect
      or inconsistent use of any method) and new sexual partnership. RESULTS: Travelers
      and pretravelers reported similar levels of contraceptive lapse (29% and 32%,
      respectively) and new sexual partnerships (17% and 12%). Multivariable analysis
      confirmed that travelers were no more likely than pretravelers to have
      contraceptive lapses, but indicated that they were more likely to report a new
      male partner (relative risk, 1.7). Most participants (80%) had a regular source
      of sexual and reproductive health care; 42% of travelers had seen a health care
      provider in preparation for their trip. CONCLUSION: If the findings are
      corroborated by additional research, they may suggest a role for health care
      providers in students' pretravel period.

PMID- 30118154
TI  - Resolving the predator first paradox: Arthropod predator food webs in pioneer
      sites of glacier forelands.
AB  - Primary succession on bare ground surrounded by intact ecosystems is, during its
      first stages, characterized by predator-dominated arthropod communities. However,
      little is known on what prey sustains these predators at the start of succession
      and which factors drive the structure of these food webs. As prey availability
      can be extremely patchy and episodic in pioneer stages, trophic networks might be
      highly variable. Moreover, the importance of allochthonous versus autochthonous
      food sources for these pioneer predators is mostly unknown. To answer these
      questions, the gut content of 1,832 arthropod predators, including four species
      of carabid beetles, two lycosid and several linyphiid spider species caught in
      early and late pioneer stages of three glacier forelands, was screened
      molecularly to track intraguild and extraguild trophic interactions among all
      major prey groups occurring in these systems. Two-thirds of the 2,310 identified
      food detections were collembolans and intraguild prey, while one-third were
      allochthonous flying insects. Predator identity and not successional stage or
      valley had by far the strongest impact on the trophic interaction patterns.
      Still, the variability of prey spectra increased significantly from early to late
      pioneer stage, as did the niche width of the predators. As such the structure of
      pioneer arthropod food webs in recently deglaciated Alpine habitats seems to be
      driven foremost by predator identity while site and early successional effects
      contribute to a lesser extent to food web variability. Our findings also suggest
      that in these pioneer sites, predatory arthropods depend less on allochthonous
      aeolian prey but are mainly sustained by prey of local production.

PMID- 30118155
TI  - Validation of three-dimensional wound measurements using a novel 3D-WAM camera.
AB  - To monitor wound healing, it is essential to obtain accurate and reliable wound
      measurements. Various methods have been used to measure wound size including
      three-dimensional (3D) measurement devices enabling wound assessment from a
      volume perspective. However, the currently available methods are inaccurate,
      costly, or complicated to use. As a consequence, we have developed a 3D-wound
      assessment monitor (WAM) camera, which is able to measure wound size in three
      dimension and to assess wound characteristics. The aim of the study was to assess
      the intrarater and interrater reliability of the 3D wound measurements using the
      3D camera and to compare these with traditional measurement methods. Four raters
      measured 48 wounds using the 3D camera, digital imaging method (2D area), and gel
      injection into the wound cavity (volume). The data were analyzed using linear
      mixed effect model. Intraclass and interclass correlation coefficient (ICC) and
      Bland-Altman plots were used to assess intrarater and interrater reliability for
      the 3D camera and agreement between the methods. The Bland-Altman plots for
      intrarater reliability showed minor differences between the measurements,
      especially the 3D area and perimeter measurements. Moreover, ICCs were very high
      for both the intrarater and interrater reliability for the 2D area, 3D area, and
      perimeter measurements (ICCs > 0.99), although slightly lower for the volume
      measurements (ICC = 0.946-0.950). Finally, a high agreement was found between the
      3D camera and the traditional methods (2D area and volume) assessed by narrow 95%
      prediction intervals and high ICCs above 0.97. In conclusion, the 3D-WAM camera
      is an accurate and reliable method, which is useful for several types of wounds.
      However, the volume measurements were primarily useful in large, deep wounds.
      Moreover, the 3D images are based on digital technology and therefore carry the
      possibility for use in remote settings.

PMID- 30118156
TI  - Effect of Semi-Fluorinated Alkyl Side Chains on Conjugated Polymers with Planar
      Backbone in Organic Field-Effect Transistors.
AB  - Newly synthesized donor-acceptor (D-A) type of conjugated copolymer (PCTV-BTzF)
      with semi-fluorinated alkyl side chains, which has good solubility in common
      organic solvents, is described. Unlike polymers with hydrocarbon-based alkyl side
      chains, semi-fluorocabonated polymer leads to intriguing results. First, the self
      organization behavior of the semi-fluoroalkyl side chains by the self-aggregate
      propensity between hydrocarbon and fluorocarbon induces patterned microstructural
      morphology in polymer films; second, it dominates the molecular orientation of
      polymers with planar back structure. Such unusual properties of the polymer with
      semi-fluoroalkyl side chains compared to that with the hydrocarbon ones are
      verified and characterized though various systematic characterizations, including
      temperature-dependent UV-Vis absorption spectroscopy, atomic force microscopy,
      and 2D-grazing incident X-ray diffraction measurement. As a result, PCTV-BTzF
      based OFETs show the maximum p-type field-effect mobility of 1.02 cm2  V-1  s-1
      in the 200  degrees C annealed films.

PMID- 30118157
TI  - Boosting Hydrogen Production by Anodic Oxidation of Primary Amines over a NiSe
      Nanorod Electrode.
AB  - For electrocatalytic water splitting, the sluggish anodic oxygen evolution
      reaction (OER) restricts the cathodic hydrogen evolution reaction (HER).
      Therefore, developing an alternative anodic reaction with accelerating kinetics
      to produce value-added chemicals, especially coupled with HER, is of great
      importance. Now, a thermodynamically more favorable primary amine (-CH2 -NH2 )
      electrooxidation catalyzed by NiSe nanorod arrays in water is reported to replace
      OER for enhancing HER. The increased H2 production can be obtained at cathode;
      meanwhile, a variety of aromatic and aliphatic primary amines are selectively
      electrooxidized to nitriles with good yields at the anode. Mechanistic
      investigations suggest that NiII /NiIII may serve as the redox active species for
      the primary amines transformation. Hydrophobic nitrile products can readily
      escape from aqueous electrolyte/electrode interface, avoiding the deactivation of
      the catalyst and thus contributing to continuous gram-scale synthesis.

PMID- 30118158
TI  - A synthetic microRNA-92a inhibitor (MRG-110) accelerates angiogenesis and wound
      healing in diabetic and nondiabetic wounds.
AB  - There is a strong unmet need for new therapeutics to accelerate wound healing
      across both chronic and acute indications. It is well established that local
      tissue hypoxia, vascular insufficiency, and/or insufficient angiogenesis
      contribute to inadequate wound repair in the context of diabetic foot ulcers as
      well as to other chronic wounds such as venous stasis and pressure ulcers.
      microRNA-92a-3p (miR-92a) is a potent antiangiogenic miRNA whose inhibition has
      led to increases in angiogenesis in multiple organ systems, resulting in an
      improvement in function following myocardial infarction, limb ischemia, vascular
      injury, and bone fracture. Due to their pro-angiogenic effects, miR-92a
      inhibitors offer potential therapeutics to accelerate the healing process in
      cutaneous wounds as well. This study investigated the effect of a development
      stage locked nucleic acid-modified miR-92a inhibitor, MRG-110, in excisional
      wounds in db/db mice and in normal pigs. In both acute and chronic wounds, MRG
      110 increased granulation tissue formation as assessed by histology, angiogenesis
      as assessed by immunohistochemistry and tissue perfusion, and wound healing as
      measured by time to closure and percent closure over time. The effects of MRG-110
      were greater than those that were observed with the positive controls rhVEGF-165
      and rhPDGF-BB, and MRG-110 was at least additive with rhPDGF-BB when co
      administered in db/db mouse wounds. MRG-110 was found to up-regulate expression
      of the pro-angiogenic miR-92a target gene integrin alpha 5 in vitro in both human
      vascular endothelial cells and primary human skin fibroblasts and in vivo in
      mouse skin, demonstrating its on-target effects in vitro and in vivo. Additional
      safety endpoints were assessed in both the mouse and pig studies with no safety
      concerns noted. These studies suggest that MRG-110 has the potential to
      accelerate both chronic and acute wound healing and these data provide support
      for future clinical trials of MRG-110.

PMID- 30118159
TI  - Differences between patient- and proxy-reported HRQoL using the Wound-QoL.
AB  - The purpose of this study was to examine the patient- and proxy-report agreement
      on the Wound-quality of life (QoL) questionnaire to assess health-related QoL in
      patients with chronic wounds. Patients and their proxies (in this case,
      relatives) were recruited via different nursing services in Germany and asked to
      complete the Wound-QoL. Intraclass correlation coefficients were calculated for
      each Wound-QoL scale and the total score, and weighted Cohen's Kappa coefficients
      for individual items. Proxies tended to report lower health-related QoL in the
      Wound-QoL than their relatives with chronic wounds. Agreement between the two
      perspectives was moderate on single-item level and excellent on scale level.
      Proxy-reports can be helpful, if patients are unable to provide information,
      although caution remains when interpreting the results. However, the patient's
      own perspective remains preferable.

PMID- 30118160
TI  - Preferred weight-related terminology by parents of children with obesity.
AB  - AIM: In order to improve weight-related discussion with patients and minimise
      their discomfort, the terminology used by medical staff should be carefully
      chosen. The aim of the study was to identify the most motivating weight-related
      terminology to use with children with obesity. METHODS: Focus groups were used to
      generate a list of 12 weight-related terms in Hebrew, sent by a questionnaire to
      parents of children and adolescents with obesity. Terms were graded according to
      how desirable, stigmatising, blaming or motivating they were perceived. We
      identified the most positive and negative weight-based terms and conducted linear
      regressions to predict child motivation to lose weight when positive terms are
      used. RESULTS: The least stigmatising and most motivating and desirable terms
      were 'unhealthy body weight' and 'unhealthy lifestyle'. Medical staff mostly used
      'overweight', which was relatively inoffensive yet not very motivating.
      'Fat/obese' ('Shamen') was the most stigmatising and blaming term and the least
      desired. Only 20% of parents endorsed a nonverbal graphical tool to describe body
      size. CONCLUSION: Our findings encourage using health-based terminology over
      weight-based terminology to promote treatment and lifestyle changes in children
      with obesity. Healthcare professionals should adopt patient-centred care and
      improve the weight-related terms they use with children with obesity.

PMID- 30118161
TI  - Natural variation in stomata size contributes to the local adaptation of water
      use efficiency in Arabidopsis thaliana.
AB  - Stomata control gas exchanges between the plant and the atmosphere. How natural
      variation in stomata size and density contributes to resolve trade-offs between
      carbon uptake and water loss in response to local climatic variation is not yet
      understood. We developed an automated confocal microscopy approach to
      characterize natural genetic variation in stomatal patterning in 330 fully
      sequenced Arabidopsis thaliana accessions collected throughout the European range
      of the species. We compared this to variation in water-use efficiency, measured
      as carbon isotope discrimination (delta13 C). We detect substantial genetic
      variation for stomata size and density segregating within Arabidopsis thaliana. A
      positive correlation between stomata size and delta13 C further suggests that
      this variation has consequences on water-use efficiency. Genome wide association
      analyses indicate a complex genetic architecture underlying not only variation in
      stomatal patterning but also to its covariation with carbon uptake parameters.
      Yet, we report two novel QTL affecting delta13 C independently of stomatal
      patterning. This suggests that, in A. thaliana, both morphological and
      physiological variants contribute to genetic variance in water-use efficiency.
      Patterns of regional differentiation and covariation with climatic parameters
      indicate that natural selection has contributed to shape some of this variation,
      especially in Southern Sweden, where water availability is more limited in spring
      relative to summer. These conditions are expected to favour the evolution of
      drought avoidance mechanisms over drought escape strategies.

PMID- 30118162
TI  - Need for Caudate duct classification: God is in the detail and so is the Devil!

PMID- 30118163
TI  - Nanoparticle-Polymer Synergies in Nanocomposite Hydrogels: From Design to
      Application.
AB  - Hydrogels are an important class of soft materials with high water retention that
      exhibit intelligent and elastic properties and have promising applications in the
      fields of biomaterials, soft machines, and artificial tissue. However, the low
      mechanical strength and limited functions of traditional chemically cross-linked
      hydrogels restrict their further applications. Natural materials that consist of
      stiff and soft components exhibit high mechanical strength and functionality.
      Among artificial soft materials, nanocomposite hydrogels are analogous to these
      natural materials because of the synergistic effects of nanoparticle (NP)
      polymers in hydrogels construction. In this article, the structural design and
      properties of nanocomposite hydrogels are summarized. Furthermore, along with the
      development of nanocomposite hydrogel-based devices, the shaping and potential
      applications of hydrogel devices in recent years are highlighted. The influence
      of the interactions between NPs and polymers on the dispersion as well as the
      structural stability of nanocomposite hydrogels is discussed, and the novel
      stimuli-responsive properties induced by the synergies between functional NPs and
      polymeric networks are reviewed. Finally, recent progress in the preparation and
      applications of nanocomposite hydrogels is highlighted. Interest in this field is
      growing, and the future and prospects of nanocomposite hydrogels are also
      reviewed.

PMID- 30118164
TI  - Patients' prediction of their wound healing time.
AB  - Understanding and managing patients' expectations can help improve their
      adherence to treatment for chronic wounds; however, little is known concerning
      about their expectations regarding healing time. Recruited subjects were asked to
      predict how long their wounds would take to heal and their charts were reviewed
      to retrieve real time of healing. We recruited 100 subjects from which 77% have
      healed. Fifty-three subjects (68.8%) had a longer healing time than they
      predicted (underestimated), and 17 (22.1%) had a shorter healing time than they
      predicted (overestimated). Subjects with shorter wound duration history tended to
      predict shorter healing time than subjects with longer wound duration (p < 0.01).
      However, wound duration did not affect prediction accuracy (p = 0.65). Subjects
      with chronic wounds seem more often to underestimate their time of healing. Wound
      duration significantly influenced patients' prediction time, although it did not
      make their prediction more accurate. Patient education about expectations may be
      important as patients often expect their wounds to heal faster than they actually
      do.

PMID- 30118165
TI  - Immunogenicity and protective efficacy of orally administered recombinant
      Lactobacillus plantarum expressing VP2 protein against IBDV in chicken.
AB  - AIM: To develop an effective oral vaccine against the very virulent infectious
      bursal disease virus (vvIBDV), we generated two recombinant Lactobacillus
      plantarum strains (pPG612-VP2/LP and pPG612-T7g10-VP2/LP, which carried the T7g10
      translational enhancer) that displayed the VP2 protein on the surface, and
      compared the humoral and cellular immune responses against vvIBDV in chickens.
      METHODS AND RESULTS: We genetically engineered the L. plantarum strains pPG612
      VP2/LP and pPG612-T7g10-VP2/LP constitutively expressing the VP2 protein of
      vvIBDV. We found that the T7g10 enhancer efficiently upregulates VP2 expression
      in pPG612-T7g10-VP2/LP. Orally administered, pPG612-T7g10-VP2/LP exhibited
      significant levels of protection (87.5%) against vvIBDV in chickens, indicating
      improved immunogenicity. Chickens in the pPG612-T7g10-VP2/LP group produced
      higher levels of interferons (IFN-gamma) and interleukins (IL-2 and IL-4) than
      those in the pPG612-VP2/LP group. CD8+ and CD4+ lymphocyte counts indicated
      greater stimulation in the pPG612-T7g10-VP2/LP group (13.3 and 21.0%
      respectively) than in the pPG612-VP2/LP group (10.4 and 14.0% respectively).
      Thus, pPG612-T7g10-VP2/LP could induce strong humoral and cellular immune
      responses against vvIBDV. CONCLUSIONS: The recombinant L. plantarum that
      expresses pPG612-T7g10-VP2 is a promising candidate for oral vaccine development
      against vvIBDV. SIGNIFICANCE AND IMPACT OF THE STUDY: The recombinant
      Lactobacillus delivery system provides a promising strategy for vaccine
      development against vvIBDV in chickens.

PMID- 30118166
TI  - Therapeutic efficacy of early photobiomodulation therapy on the zones of stasis
      in burns: An experimental rat model study.
AB  - This study aimed to investigate the role of photobiomodulation therapy in
      preventing zones of stasis in burn wounds. We hypothesized that
      photobiomodulation therapy could promote tissue formation and release of nitric
      oxide (NO), and reduce inflammatory responses, thereby dilating local
      microvessels, reducing necrosis and apoptosis. Thirty rats were randomly divided
      into control group (CG) and laser group (LG). The zone of stasis was formed by
      applying a brass comb to the skin resulting in four rectangular burns separated
      by three unburned interspaces. The left side was laser wound (LW), while the
      right side was shielded wound (SW). The LW of LG was immediately subjected to
      photobiomodulation therapy, followed by once-daily 30-minutes photobiomodulation
      therapy sessions. Skin ultrasound and Doppler angiography analyses were used to
      evaluate the statuses of the zones of stasis at 1, 24, and 96 hours after injury.
      Harvested burn wound tissue was subjected to hematoxylin-eosin staining and
      HMGB1, caspase 3, and thrombomodulin immunohistochemistry, and the contents of NO
      and TNF-alpha were measured in stasis tissue. Thrombomodulin, HMGB1, and caspase
      3 immunohistochemistry revealed significantly lower positive staining rates in
      the LW of LG rats relative to the others at 96 hours (p < 0.05), as well as a
      significantly higher skin blood flow relative to the others (p < 0.05). The NO
      content was significantly higher in the LW of LG, compared with other wounds, at
      24 and 96 hours after injury (p < 0.05). The TNF-alpha level was significantly
      lower in the LW of LG than in other wounds at 96 hours (p < 0.05). Early, local
      photobiomodulation therapy can effectively ameliorate injury progression in the
      zone of stasis. However, these beneficial effects are limited to the directly
      irradiated sites.

PMID- 30118167
TI  - Neuronal correlates of motion-defined shape perception in primate dorsal and
      ventral streams.
AB  - Human and non-human primates can readily perceive the shape of objects using
      visual motion. Classically, shape, and motion are considered to be separately
      processed via ventral and dorsal cortical pathways, respectively. However, many
      lines of anatomical and physiological evidence have indicated that these two
      pathways are likely to be interconnected at some stage. For motion-defined shape
      perception, these two pathways should interact with each other because the
      ventral pathway must utilize motion, which the dorsal pathway processes, to
      extract shape signal. However, it is unknown how interactions between cortical
      pathways are involved in neural mechanisms underlying motion-defined shape
      perception. We review evidence from psychophysical, lesion, neuroimaging and
      physiological research on motion-defined shape perception and then discuss the
      effects of behavioral demands on neural activity in ventral and dorsal cortical
      areas. Further, we discuss functions of two candidate sets of levels: early and
      higher-order cortical areas. The extrastriate area V4 and middle temporal (MT)
      area, which are reciprocally connected, at the early level are plausible areas
      for extracting the shape and/or constituent parts of shape from motion cues
      because neural dynamics are different from those during luminance-defined shape
      perception. On the other hand, among other higher-order visual areas, the
      anterior superior temporal sulcus likely contributes to the processing of cue
      invariant shape recognition rather than cue-dependent shape processing. We
      suggest that sharing information about motion and shape between the early visual
      areas in the dorsal and ventral pathways is dependent on visual cues and
      behavioral requirements, indicating the interplay between the pathways.

PMID- 30118168
TI  - Functional Precision Polymers via Stereo- and Regioselective Polymerization Using
      Group 6 Metal Alkylidene and Group 6 and 8 Metal Alkylidene N-Heterocyclic
      Carbene Complexes.
AB  - The concepts of functional precision polymers and the latest accomplishments in
      their synthesis are summarized. Synthetic concepts based on chain growth
      polymerization are compared to iterative synthetic approaches. Here, the term
      "functional precision polymers" refers to polymers that are not solely
      hydrocarbon-based but contain functional groups and are characterized by a highly
      ordered primary structure. If insertion polymerization is used for their
      synthesis, olefin metathesis-based polymerization techniques, that is, ring
      opening metathesis polymerization (ROMP), acyclic diene metathesis (ADMET)
      polymerization, and the regio- and stereoselective cyclopolymerization of
      alpha,omega-diynes are almost exclusively applied. Particularly with regio- and
      stereospecific ROMP and with cyclopolymerization, the synthesis of tactic
      polymers and copolymers with high regio-, stereo-, and sequence control can be
      accomplished; however, it requires carefully tailored transition metal catalysts.
      The fundamental synthetic concepts and strategies are outlined.

PMID- 30118169
TI  - L-DOPA for Parkinson's disease-a bittersweet pill.
AB  - 3,4-dihydroxy-L-phenylalanine (L-DOPA) is the gold standard treatment for
      Parkinson's disease. It has earned that title through its highly effective
      treatment of some of the motor symptoms in the early stages of the disease but it
      is a far from perfect drug. The inevitable long-term treatment that comes with
      this chronic neurodegenerative condition raises the risk significantly of the
      development of motor fluctuations including disabling L-DOPA-induced dyskinesia.
      Being unsurpassed as a therapy means that understanding the mechanisms of
      dyskinesia priming and induction is vital to the search for therapies to treat
      these side effects and allow optimal use of L-DOPA. However, L-DOPA use may also
      have consequences (positive or negative) for the development of other
      interventions, such as cell transplantation, which are designed to treat or
      repair the ailing brain. This review looks at the issues around the use of L-DOPA
      with a focus on its potential impact on advanced reparative interventions.

PMID- 30118170
TI  - Exogenous Amino Acid-Loaded Nanovehicles: Stepping across Endogenous Magnetic
      Resonance Spectroscopy.
AB  - Magnetic resonance spectroscopy (MRS) allows the assessment of metabolic contents
      and biochemical information in vivo. It provides essential compositional
      information in the diagnosis and monitoring of central nervous system (CNS)
      diseases, especially brain tumors. Conventional MRS is usually confined to
      endogenous metabolites that may lack specificity for certain disease such as
      differentiating glioma from other tumor and non-tumorous lesions. Therefore,
      exogenous MRS contrast agents (CAs) that may improve the sensitivity and
      specificity of MRS are highly desirable for its clinical use. In this work, a
      novel MRS CA, beta-alanine loaded hollow mesoporous silica nanospheres, with a
      high biosafety profile and characteristic MRS spectrum was synthesized and
      investigated. This new CA is further tested to realize the accurate functional
      MRS diagnosis of brain glioma with high sensitivity. The general approach of
      synthesizing disease specific CA for MRS may lead to a new era of molecular
      imaging.

PMID- 30118171
TI  - Multinational validation of the American Joint Committee on Cancer 8th edition
      pancreatic cancer staging system in a pancreas head cancer cohort.
AB  - BACKGROUND: The aim of the present study was to compare the 7th and 8th editions
      of the American Joint Committee on Cancer (AJCC) staging system for pancreas head
      cancer and to validate the 8th edition using three multinational tertiary center
      data. METHODS: Data of 2,864 patients with pancreas head cancer were collected
      from Korea (571), Japan (824), and the USA (1,469). Survival analysis was
      performed to compare the 7th and 8th editions. Validation was performed by log
      rank tests and test for trend repeated 1,000 times with random sets. RESULTS: In
      the 7th edition, 4.1%, 3.1%, 18.6%, 67.5%, 3.6%, and 3.1% were stage IA, IB, IIA,
      IIB, III, and IV. In the 8th edition, 8.8%, 13.9%, 3.1%, 38.2%, 32.9%, and 3.1%
      were stage IA, IB, IIA, IIB, III, and IV, respectively. The change in T category
      downstaged 459 patients from IIA to the new IA and IB. The new N2 category
      upstaged 856 patients from the former IIB to III. The 7th edition reversely
      stratified IA and IB. The 8th edition corrected this mis-stratification of the
      7th edition, but lacked discriminatory power between IB and IIA (P = 0.271).
      Validation using the log-rank showed that the 8th edition provided better
      discrimination in 6.387 test sets among 10 tests. The test for trend validated
      the 8th edition to stratify stages in correct order more often (7.815/10).
      CONCLUSION: The 8th edition provides more even distribution with more powerful
      discrimination compared to the 7th edition.

PMID- 30118172
TI  - Synthetic isoflavones and doping: A novel class of aromatase inhibitors?
AB  - Anectodical information suggests that flavonoids may be widely used among
      athletes for their multiple biochemical and pharmacological effects. We have
      evaluated in vitro the effects of two synthetic isoflavones, methoxyisoflavone
      and ipriflavone, on the catalytic activity of human aromatase (CYP19), the enzyme
      catalyzing the conversion of androgens (ie, testosterone or androstenedione) to
      estrogens (ie, estradiol and estrone). The potential inhibitory effect was
      evaluated by measuring the rate of aromatization of testosterone, monitored by
      gas chromatography-mass spectrometry (GC-MS), both in the presence and in the
      absence of methoxyisoflavone or ipriflavone, comparing their effects with those
      of synthetic aromatase inhibitors (formestane, anastrozole, and
      aminoglutethimide) presently included in the list of prohibited substances and
      methods, and of natural flavonoids (chrysin, quercetin, and daidzein), that are
      known inhibitors of CYP19. The preliminary results of our in vitro study show
      that methoxyisoflavone and ipriflavone act as competitive inhibitors of
      aromatase, the degree of inhibition measured in vitro being of the same order of
      magnitude of that of the aromatase inhibitors commonly used in anti-estrogenic
      therapies. Our preliminary in vitro results indicate that, in principle, a
      sufficiently large intake of isoflavones could alter the kinetics of the dynamic
      equilibria between androgens and estrogens, suggesting their monitoring in doping
      control routine analysis.

PMID- 30118173
TI  - Nasal polyp fibroblasts modulate epithelial characteristics via Wnt signaling.
AB  - BACKGROUND: While essential to the normal differentiation of ciliated airway
      epithelial cells, upregulated Wnt signaling in chronic rhinosinusitis with nasal
      polyps (CRSwNP) has been proposed to result in abnormal epithelial morphology and
      dysfunctional mucociliary clearance. The mechanism of epithelial Wnt signaling
      dysregulation in CRSwNP is unknown, and importantly cellular sources of Wnt
      ligands in CRSwNP have not yet been investigated. METHODS: Human sinonasal
      epithelial cells (hSNECs) and human sinonasal fibroblasts (hSNFs) were collected
      from 34 human subjects (25 control and 9 CRSwNP) and differentiated as primary
      air-liquid interface (ALI) and organoid co-cultures. hSNECs were isolated to the
      apical compartment of the transwell and hSNFs were isolated to the basolateral
      compartment. After 21 days of ALI culture, ciliary expression and sinonasal
      epithelial morphology were examined by immunohistochemistry (IHC) and
      quantitative real-time polymerase chain reaction (qRT-PCR). An organoid model was
      used to evaluate proliferation of basal cells in presence of hSNFs. RESULTS:
      Epithelial cells co-cultured with CRSwNP-hSNFs revealed significantly decreased
      ciliated cells, altered epithelial cell morphology, and increased colony forming
      efficiency compared to epithelial cells co-cultured with control-hSNFs. CRSwNP
      hSNFs showed significantly higher messenger RNA (mRNA) expression of canonical
      WNT3A. A Wnt agonist, CHIR99021, replicated CRSwNP-hSNF co-cultures, and
      treatment with the Wnt inhibitor IWP2 prevented abnormal morphologies.
      CONCLUSION: These results suggest that abnormal interactions between epithelial
      cells and fibroblasts may contribute to CRSwNP pathogenesis and supports the
      concept that dysregulated Wnt signaling contributes impairment to epithelial
      function in CRSwNP.

PMID- 30118174
TI  - Caffeine and supplemental oxygen effectively suppress periodic breathing with
      only minor effects during long episodes of apnoea in preterm infants.
AB  - AIM: We investigated the characteristics and effects of sleep stage, supplemental
      oxygen and caffeine on periodic breathing (PB) and apnoea of prematurity (AOP) in
      preterm infants. METHODS: This 2013-2015 study recruited 21 preterm infants on
      neonatal wards in the Helsinki and Uusimaa Hospital District, Finland, at a
      median corrected gestational age of 35.7 weeks and performed polysomnography at
      baseline, during supplemental oxygen and during caffeine treatment. RESULTS: All
      infants demonstrated PB, during a median of 11% of sleep time and 85% of PB
      occurred during non-rapid eye movement sleep (NREM). Apnoea episodes were brief
      during PB, but 66% were associated with oxygen desaturation. Supplemental oxygen
      substantially reduced PB time by 99% and caffeine by 91%. Oxygen desaturation
      decreased from 38 per hour at baseline to 8.5 with oxygen and 24 with caffeine
      (all p < 0.001). AOPs decreased from 1.4 per hour at baseline to 0.4 with oxygen
      (p = 0.03) and 0.3 with caffeine (p = 0.07). Most (84%) apnoea episodes over 15
      seconds were mixed episodes during REM sleep. CONCLUSION: PB occurred
      predominantly during NREM sleep, caused intermittent hypoxia, and was suppressed
      by supplemental oxygen and caffeine. In contrast, long apnoea episodes
      representing AOP were only modestly decreased.

PMID- 30118175
TI  - Operative time and cost variability for functional endoscopic sinus surgery.
AB  - BACKGROUND: Understanding the variation in costs of endoscopic sinus surgery
      (ESS) is critical to defining value. Current published costs of ESS have not
      identified potential sources of variation. Our objective was to analyze ESS costs
      to identify sources of variance that could guide value-improving decisions.
      METHODS: ESS cases (n = 1739) performed between 2008 and 2016 were identified
      from a database of 22 rural to tertiary facilities. Cost and time data were
      extracted from the database. Medical records were reviewed to confirm procedures.
      Three bilateral groupings were examined (n = 895 cases from 13 facilities): (1)
      full ESS (all sinuses); (2) intermediate ESS (total ethmoid, maxillary); and (3)
      anterior ESS (anterior ethmoid, maxillary). Cost and operative time were analyzed
      using multivariable gamma regression. RESULTS: Median costs for full,
      intermediate, and anterior ESS were $4281, $3716, and $2549 U.S. dollars (p <
      0.001). Median durations were 87, 60, and 58 minutes (p < 0.001). Among patients
      with no additional procedures, those with full ESS had operative duration, total
      cost, and supply costs that were 1.37 (95% confidence interval [CI], 1.17 to
      1.61), 1.52 (95% CI, 1.32 to 1.75), and 2.40 (95% CI, 1.76 to 3.25) times greater
      than anterior ESS, respectively (all p < 0.001). Intermediate ESS duration at
      community urban facilities was 1.87 (95% CI, 1.74 to 2.02) times that of
      community rural facilities (p < 0.001). CONCLUSION: Duration of surgery, extent
      of surgery, and location of surgery are sources of significant variation in the
      cost of ESS. These findings will assist healthcare policy makers, hospitals, and
      surgeons in optimizing the value of ESS.

PMID- 30118176
TI  - Gestational chronodisruption leads to persistent changes in the rat fetal and
      adult adrenal clock and function.
AB  - KEY POINTS: Light at night is essential to a 24/7 society, but it has negative
      consequences on health. Basically, light at night induces an alteration of our
      biological clocks, known as chronodisruption, with effects even when this occurs
      during pregnancy. Here we explored the developmental impact of gestational
      chronodisruption (chronic photoperiod shift, CPS) on adult and fetal adrenal
      biorhythms and function. We found that gestational chronodisruption altered fetal
      and adult adrenal function, at the molecular, morphological and physiological
      levels. The differences between control and CPS offspring suggest
      desynchronization of the adrenal circadian clock and steroidogenic pathway,
      leading to abnormal stress responses and metabolic adaptation, potentially
      increasing the risk of developing chronic diseases. ABSTRACT: Light at night is
      essential to a 24/7 society, but it has negative consequences on health.
      Basically, light at night induces an alteration of our biological clocks, known
      as chronodisruption, with effects even when this occurs during pregnancy. Indeed,
      an abnormal photoperiod during gestation alters fetal development, inducing long
      term effects on the offspring. Accordingly, we carried out a longitudinal study
      in rats, exploring the impact of gestational chronodisruption on the adrenal
      biorhythms and function of the offspring. Adult rats (90 days old) gestated under
      chronic photoperiod shift (CPS) decrease the time spent in the open arm zone of
      an elevated plus maze to 62% and increase the rearing time to 170%. CPS adults
      maintained individual daily changes in corticosterone, but their acrophases were
      distributed from 12.00 h to 06.00 h. CPS offspring maintained clock gene
      expression and oscillation, nevertheless no daily rhythm was observed in genes
      involved in the regulation and synthesis of steroids. Consistent with adult
      adrenal gland being programmed during fetal life, blunted daily rhythms of
      corticosterone, core clock gene machinery, and steroidogenic genes were observed
      in CPS fetal adrenal glands. Comparisons of the global transcriptome of CPS
      versus control fetal adrenal gland revealed that 1078 genes were differentially
      expressed (641 down-regulated and 437 up-regulated). In silico analysis revealed
      significant changes in Lipid Metabolism, Small Molecule Biochemistry, Cellular
      Development and the Inflammatory Response pathway (z score: 48-20). Altogether,
      the present results demonstrate that gestational chronodisruption changed fetal
      and adult adrenal function. This could translate to long-term abnormal stress
      responses and metabolic adaptation, increasing the risk of developing chronic
      diseases.

PMID- 30118178
TI  - Free radical damage can cause serious long-lasting effects.

PMID- 30118177
TI  - Data-driven respiratory motion compensation for four-dimensional cone-beam
      computed tomography (4D-CBCT) using groupwise deformable registration.
AB  - PURPOSE: To demonstrate the feasibility of using a purely data-driven, a
      posteriori respiratory motion modeling and reconstruction compensation method to
      improve 4D-CBCT image quality under clinically relevant image acquisition
      conditions. METHODS: Evaluated workflows that utilized a combination of groupwise
      deformable image registration and motion-compensated image reconstruction
      algorithms. Groupwise registration is an approach that simultaneously registers
      all temporal frames of a 4D image to a common reference instead of one at a time
      so as to minimize the influence of any individual time point on the global
      smoothness or accuracy of the resulting deformation model. Four-dimensional cone
      beam CT (4D-CBCT) Feldkamp-Davis-Kress (FDK) reconstructions were registered to
      either iteratively computed mean respiratory phase (mean-frame) or preselected
      respiratory phase (fixed-frame) reference images to model respiratory motion. The
      resulting 4D transformations were used to deform projection data during the FDK
      backprojection operation to create motion-compensated reconstructions. Tissue
      interface sharpness (TIS) was defined as the slope of a sigmoid curve fit to a
      mobile tissue boundary and was used to evaluate image quality in regions
      susceptible to motion artifacts. Image quality improvement was assessed for 19
      clinical cases by evaluating mitigation of view aliasing artifacts, TIS, image
      noise reduction, and contrast for implanted fiducial markers. RESULTS: Average
      (standard deviation) diaphragm TIS recovery relative to initial 4D-CBCT
      reconstructions was observed to be 87% (46%) using fixed-frame registration
      alone; 87% (47%) using fixed frame with motion-compensated reconstruction; 101%
      (68%) using mean-frame registration alone; and 99% (65%) using mean frame with
      motion-compensated reconstruction. Noise was reduced in sampled soft tissue ROIs
      by 58% for both fixed-frame registration and registration with motion
      compensation and by 57% and 58% on average for the corresponding mean-frame
      methods, respectively. Average improvement in local CNR was observed to be
      respectively 93% and 98% for fixed-frame registration and registration with
      motion compensation methods and 116% and 111% for the corresponding mean-frame
      methods. CONCLUSION: Data-driven groupwise registration and motion-compensated
      reconstruction offer a feasible means of improving the quality of 4D-CBCT images
      acquired under clinical conditions. The addition of motion compensation
      reconstruction after groupwise registration visibly reduced the impact of view
      aliasing artifacts for the clinical image datasets studied.

PMID- 30118179
TI  - Emotion-focused therapy for binge-eating disorder: A review of six cases.
AB  - OBJECTIVE: This study aimed to provide preliminary evidence of the usefulness of
      emotion-focused therapy (EFT) for binge-eating disorder (BED). METHODS: We used a
      single-subject design in which 12 weeks of individual EFT were applied
      nonconcurrently to six female adult participants with BED, following three weekly
      baseline sessions. Participants were assessed for binge-eating psychopathology
      and emotion regulation difficulties on a weekly basis during baseline and
      treatment. They were assessed on a 2-, 4-, and 8-week basis during posttreatment,
      and they were assessed for binge-eating episodes, eating disorder attitudes,
      alexithymia, and psychiatric comorbidity at pretreatment and posttreatment.
      RESULTS: All cases experienced reliable recovery from binge-eating
      psychopathology and a significant decrease in binge-eating frequency. For all
      cases, there was reliable improvement or recovery on eating and shape concerns,
      and there was improvement on weight concern for the majority of cases. For all
      cases, reliable recovery or improvement occurred in overall emotion regulation.
      Most cases that were in the clinical range pretreatment recovered for anxiety,
      and reliable improvement in or recovery from depression occurred for all cases.
      There was reliable recovery or improvement in alexithymia for half of the cases;
      however, the other half experienced no change or deteriorated. There were no
      treatment dropouts. CONCLUSION: Individual EFT demonstrates potential as a
      psychological treatment for BED. The current study provides preliminary evidence
      to guide the development of a more extensive trial to test the efficacy of
      individual EFT for BED as well as to identify possible mechanisms of change.

PMID- 30118180
TI  - Quantitative and qualitative assessment of pollen DNA metabarcoding using
      constructed species mixtures.
AB  - Pollen DNA metabarcoding-marker-based genetic identification of potentially mixed
      species pollen samples-has applications across a variety of fields. While basic
      species-level pollen identification using standard DNA barcode markers is
      established, the extent to which metabarcoding (a) correctly assigns species
      identities to mixes (qualitative matching) and (b) generates sequence reads
      proportionally to their relative abundance in a sample (quantitative matching) is
      unclear, as these have not been assessed relative to known standards. We tested
      the quantitative and qualitative robustness of metabarcoding in constructed
      pollen mixtures varying in species richness (1-9 species), taxonomic relatedness
      (within genera to across class) and rarity (5%-100% of grains), using Illumina
      MiSeq with the markers rbcL and ITS2. Qualitatively, species composition
      determinations were largely correct, but false positives and negatives occurred.
      False negatives were typically driven by lack of a barcode gap or rarity in a
      sample. Species richness and taxonomic relatedness, however, did not strongly
      impact correct determinations. False positives were likely driven by
      contamination, chimeric sequences and/or misidentification by the bioinformatics
      pipeline. Quantitatively, the proportion of reads for each species was only
      weakly correlated with its relative abundance, in contrast to suggestions from
      some other studies. Quantitative mismatches are not correctable by consistent
      scaling factors, but instead are context-dependent on the other species present
      in a sample. Together, our results show that metabarcoding is largely robust for
      determining pollen presence/absence but that sequence reads should not be used to
      infer relative abundance of pollen grains.

PMID- 30118181
TI  - Photoinitiated Seeded RAFT Dispersion Polymerization: A Facile Method for the
      Preparation of Epoxy-Functionalized Triblock Copolymer Nano-Objects.
AB  - In this study, a novel photoinitiated seeded reversible addition-fragmentation
      chain transfer (RAFT) dispersion polymerization is developed for the preparation
      of epoxy-functionalized triblock copolymer nano-objects at room temperature.
      Epoxy-functionalized worms and vesicles prepared by photoinitiated RAFT
      dispersion polymerization of glycidyl methacrylate are used as seeds for chain
      extension by photoinitiated seeded RAFT dispersion polymerization of methacrylic
      and acrylic monomers. Good control is maintained during the polymerization with a
      high polymerization rate. Pure triblock copolymer worms can be prepared by the
      photoinitiated seeded RAFT dispersion polymerization with a broad degree of
      polymerization range of the third block. The room temperature feature of
      photoinitiated seeded RAFT dispersion polymerization is critical to ensure the
      survival of epoxy moiety after the polymerization. The obtained triblock
      copolymer nano-objects can be cross-linked by reacting with a diamine. Finally,
      cross-linked worms are used as the stationary phase of chromatography for
      selective separation of organic dyes from water.

PMID- 30118182
TI  - Prevalence and pathogenesis of osteopenia and osteoporosis in epidermolysis
      bullosa: An evidence-based review.
AB  - BACKGROUND: Osteopenia or osteoporosis is one of the many comorbidities in
      patients with Epidermolysis Bullosa (EB). Current literature on the prevalence of
      osteoporosis in EB is scarce. OBJECTIVE: This review will analyse the current
      literature in the field of patients with compromised bone health in EB and any
      articles on the prevalence of such diseases in EB groups. METHODS: A systematic
      search for articles related to bone health and epidermolysis bullosa (EB) (1946
      2017) was performed on seven databases: MEDLINE, EMBASE and EBM, PubMed,
      ProQuest, Scopus and Web of Science. Search terms: epidermolysis bullosa,
      osteop*, bone mass, bone mineral*, fracture, dual X-ray absorptiometry, vitamin
      D, calcium, nutrition, exercise and physical activity. Abstracts from all search
      results were screened, and reference scanning of the search results was
      performed. Eighty-three articles met the selection criteria and were considered
      for review. Letters to the editor and abstract-only articles were excluded.
      Articles were favoured based on citation count, impact factor of their journal
      and study sample size. The search included all languages. RESULTS: The searches
      yielded a total of 1309 articles including 717 duplicates. The remaining 592
      articles were screened by title and abstracts. Eighty-three full-text articles
      were analysed. Twenty-one articles directly relating to bone health in EB were
      included. Three descriptive studies and one case-control study were found,
      indicating a need for research of larger scale. CONCLUSION: Further
      investigations into osteoporosis in EB, especially the milder forms of EB, are
      valuable in providing evidence to support guideline developments for EB bone
      health management.

PMID- 30118184
TI  - Dissemination of exposure in the treatment of anxiety disorders and post
      traumatic stress disorder among German cognitive behavioural therapists.
AB  - The efficacy of exposure is beyond doubt, which is reflected in guidelines
      recommending its application in the treatment of anxiety disorders and post
      traumatic stress disorder (PTSD). Research suggests exposure to be underutilized
      in clinical practice in the United States and Europe. A systematic investigation
      of the dissemination of exposure in Germany is lacking. The present study
      examined the dissemination and application frequency of exposure among German
      cognitive behavioural therapists working in routine care. In an online-based
      survey, 331 psychotherapists provided information on treatment of patients with
      panic disorder, phobia, and PTSD. By means of multinomial logistic regression
      analysis, application frequency of exposure (non-users vs. users vs. frequent
      users) was predicted by various therapist characteristics. Younger age and less
      negative beliefs about exposure significantly predicted the affiliation to the
      frequent users group compared to the non-users in the treatment of panic disorder
      or phobia. Concerning treatment of PTSD, only negative beliefs about exposure was
      identified as significant predictor. Sex, educational level, and number of
      exposure sessions performed during clinical training were not of predictive
      value. Current findings suggest that negative beliefs about exposure and age
      impact the frequent provision of exposure to patients. Modification of negative
      attitudes might be achieved through specific training strategies.

PMID- 30118185
TI  - Diatom Silica for Biomedical Applications: Recent Progress and Advances.
AB  - Diatoms are unicellular photosynthetic algae enclosed in porous 3D nanopatterned
      silica enclosures called "frustules." The diatom frustules are made from
      biosilica self-assembled into intricate porous shells that feature unique
      properties including high specific surface area, biocompatibility, tailorable
      surface chemistry, thermal stability, and high mechanical and chemical
      resistance. The ability to cultivate diatoms in artificial environments and their
      abundant availability of diatom frustules as mineable fossilized mineral deposits
      (diatomite or diatomaceous earth; DE) make diatom silica a promising natural
      alternative to synthetic porous silica for a broad range of biomedical,
      environmental, agricultural, and energy applications. This review article
      provides a comprehensive and current account of the use of natural DE silica
      materials in biomedical applications focused mainly on drug delivery with some
      highlights on biosensing, tissue engineering, and clotting agents. The article
      also covers some basic physical and chemical aspects of DE material such as
      purification, surface chemical functionalization, biocompatibility, and cellular
      uptake that are critical for the development of an efficient drug carrier.

PMID- 30118183
TI  - Glycogen synthase kinase-3 and alternative splicing.
AB  - Glycogen synthase kinase-3 (GSK-3) is a highly conserved negative regulator of
      receptor tyrosine kinase, cytokine, and Wnt signaling pathways. Stimulation of
      these pathways inhibits GSK-3 to modulate diverse downstream effectors that
      include transcription factors, nutrient sensors, glycogen synthesis,
      mitochondrial function, circadian rhythm, and cell fate. GSK-3 also regulates
      alternative splicing in response to T-cell receptor activation, and recent
      phosphoproteomic studies have revealed that multiple splicing factors and
      regulators of RNA biosynthesis are phosphorylated in a GSK-3-dependent manner.
      Furthermore, inhibition of GSK-3 alters the splicing of hundreds of mRNAs,
      indicating a broad role for GSK-3 in the regulation of RNA processing. GSK-3
      regulated phosphoproteins include SF3B1, SRSF2, PSF, RBM8A, nucleophosmin 1
      (NPM1), and PHF6, many of which are mutated in leukemia and myelodysplasia. As
      GSK-3 is inhibited by pathways that are pathologically activated in leukemia and
      loss of Gsk3 in hematopoietic cells causes a severe myelodysplastic neoplasm in
      mice, these findings strongly implicate GSK-3 as a critical regulator of mRNA
      processing in normal and malignant hematopoiesis. This article is categorized
      under: RNA Processing > Splicing Mechanisms RNA Processing > Splicing
      Regulation/Alternative Splicing RNA in Disease and Development > RNA in Disease
      RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions:
      Functional Implications.

PMID- 30118186
TI  - Suitability evaluation of new endogenous biomarkers for the identification of
      nitrite-based urine adulteration in mass spectrometry methods.
AB  - Urine adulteration to circumvent positive drug testing is a fundamental challenge
      for toxicological laboratories all over the world. Untargeted mass spectrometry
      (MS) methods used in metabolomics had previously revealed uric acid (UA),
      histidine, methylhistidine, and their oxidation products, for example 5
      hydroxyisourate (HIU) as potential biomarkers for urine adulteration using
      potassium nitrite (KNO2 ). These markers should be further evaluated for their
      reliability, stability, and routine applicability. Influence of KNO2
      concentration, urinary pH, reaction time, and stability at room temperature, 4
      degrees C, and - 20 degrees C was determined in urine under varying conditions.
      Analysis was performed after protein precipitation with acetonitrile by liquid
      chromatography-high resolution mass spectrometry (LC-HRMS). Receiver operating
      characteristics (ROC) analysis was applied for cut-off evaluation after biomarker
      quantification (n = 100 per group). Blinded measurements (n = 50) were performed
      to check the general applicability to identify adulterated samples under routine
      conditions. The higher the adulterant concentration, the lower the concentrations
      of histidine, methylhistidine, and UA. In return, amounts of their oxidation
      products increased. Highest changes were observed under weak acid conditions (pH
      4-5). Storage at -20 degrees C ensured sufficient stability for all oxidative
      markers over one month. ROC evaluated biomarker performance and application to
      unknown samples revealed satisfying results, with HIU as the most suitable
      biomarker (positive predictive value (PPV) 100%), followed by UA (PPV 93%). HIU
      and UA proved suitable markers to identify urine adulteration using KNO2 and are
      ready for implementation into routine MS procedures.

PMID- 30118187
TI  - Finding the metabolic stress 'sweet spot': implications for sprint interval
      training-induced muscle remodelling.

PMID- 30118188
TI  - Reducing classroom temperature in a tropical climate improved the thermal comfort
      and the performance of elementary school pupils.
AB  - A two-week-long intervention study was performed in two classrooms in an
      elementary school in Costa Rica. Split-cooling air-conditioning (AC) units were
      installed in both classrooms. During the first week, the air temperature was
      reduced in one classroom while in the other (placebo) classroom the fans were
      operated but no cooling was provided. During the second week, the conditions were
      exchanged to create a 2 * 2 crossover design in which each pupil was their own
      control. A total of 37 children performed tasks similar to school work and
      completed questionnaires reporting their thermal sensation and perceptions.
      Operating the AC units reduced classroom temperature by about 5 K, from about 30
      to 25 degrees C. Thermal sensations changed from hot to neutral and slightly
      cold, and the percentage of children rating the thermal conditions as acceptable
      increased significantly. Neutral temperature was estimated to be about 27 degrees
      C. The 11-year-old children performed the language and logical-thinking tasks
      significantly better in terms of speed at the lower temperature, while the less
      able pupils performed better on all tasks at the lower temperature. There were no
      significant effects on accuracy. These results confirm published findings from
      moderate climates and extend their validity to the tropics. They indicate that
      acclimatization can increase the optimal temperature for learning.

PMID- 30118189
TI  - Prosection or Dissection: Which is Best for Teaching the Anatomy of the Hand and
      Foot?
AB  - Due to the current trend of decreasing contact hours and less emphasis being
      given to the basic science courses in the pre-clinical years of medical
      education, it is essential that new approaches to teaching gross anatomy are
      investigated to ensure medical students are being adequately exposed to
      anatomical content. This study retrospectively analyzed practical examination
      data from four medical gross anatomy classes (N = 569) to ascertain which
      pedagogical approach, student participation in the dissection process, or
      interaction with prosected specimens is best for teaching the anatomy of the hand
      and foot. Data analysis involved the use of propensity score matching, a
      nonparametric preprocessing statistical approach which ensures accurate
      representation of the true treatment effect by balancing cohorts prior to
      statistical analysis. Statistical analysis indicated that those students who were
      exposed to the anatomy of the hand through interactions with prosected specimens
      performed 5.6% better (P= 0.012) while for the foot, students who interacted with
      prosections performed 13.0% better (P< 0.001). Although limited, data from this
      study suggest that utilizing prosections of the hand and foot seems to be a more
      advantageous pedagogical approach for teaching these regions than requiring
      students to dissect them.

PMID- 30118190
TI  - Reply from authors: RE: Bone heat generated using conventional implant drills
      versus piezosurgery unit during apical cortical plate perforation.

PMID- 30118191
TI  - Cardiometabolic risk factors differ among adolescents with obesity in three
      European countries - a cross-sectional study.
AB  - AIM: We aimed to compare modifiable cardiometabolic risk factors among treatment
      seeking adolescents with obesity in Italy, Germany and Norway. METHODS: This
      retrospective, registry-based, cross-sectional cohort study included 2,327 (59%
      girls) 12-18 year-old adolescents with obesity from three tertiary care
      outpatient clinics in Europe, between 1999 and 2015. The prevalence of
      cardiometabolic risk factors was compared between clinics, and multivariate
      logistic regression models including gender, age, waist circumference and body
      mass index were used to assess the associations between population and
      cardiometabolic risk. RESULTS: In total, 1,396 adolescents (60% girls) from
      Italy, 654 (58% girls) from Germany and 277 (51% girls) from Norway were
      included. The mean +/- SD age was 15.2 +/- 1.6 years, body mass index 38.8 +/-
      6.5 kg/m2 and body mass index standard deviation score 3.21 +/- 0.43. The
      prevalence of elevated nonhigh-density lipoprotein-cholesterol in Norway, Germany
      and Italy was 60%, 54% and 45%, while the prevalence of high systolic or
      diastolic blood pressure (>=130 or >=85 mmHg) were 15%, 46% and 66%,
      respectively. CONCLUSION: Cardiometabolic risk factors among treatment-seeking
      adolescents with obesity from Italy, Germany and Norway differed across the
      populations in this study, which might imply that preventive clinical work should
      reflect such differences.

PMID- 30118192
TI  - Design, synthesis, and evaluation of novel diphenyl ether derivatives against
      drug-susceptible and drug-resistant strains of Mycobacterium tuberculosis.
AB  - In our efforts to develop druggable diphenyl ethers as potential antitubercular
      agents, a series of novel diphenyl ether derivatives (5a-f, 6a-f) were designed
      and synthesized. The representative compounds showed promising in vitro activity
      against drug-susceptible, isoniazid-resistant, and multidrug-resistant strains of
      Mycobacterium tuberculosis with MIC values of 1.56 MUg/ml (6b), 6.25 MUg/ml (6a
      d), and 3.125 MUg/ml (6b-c), respectively. All the synthesized compounds
      exhibited satisfactory safety profile (CC50  > 300 MUg/ml) against Vero and HepG2
      cells. Reverse phase HPLC method was used to probe the physicochemical properties
      of the synthesized compounds. This series of compounds demonstrated comparatively
      low logP values. pKa values of representative compounds indicated that they were
      weak acids. Additionally, in vitro human liver microsomal stability assay
      confirmed that the synthesized compounds possessed acceptable stability under
      study conditions. The present study thus establishes compound 6b as the most
      promising antitubercular agent with acceptable drug-likeness.

PMID- 30118193
TI  - Author's Response

PMID- 30118194
TI  - Seminal profile of 23,504 patients over the years: 7 years of experience.
AB  - OBJECTIVE: To evaluate the behavior of seminal parameters over the years - 2010
      to May 2017. METHODS : A retrospective study, carried out from January 2010 to
      May 2017, covering men who underwent sperm examination. Seminal parameters
      (volume, sperm concentration, motility, morphology, age and duration of
      infertility in years) of 23,504 men were evaluated. The groups were compared to
      each other to check whether there were changes to the seminal parameters in that
      period. RESULTS : There was no change over the years considering the time of
      infertility, in an average of 3.78 years. The mean age of the patients was 36.53
      years, with a trend of increase in 0.2 years. In relation to the volume of semen
      samples, the mean value was 3.29mL, with a decrease trend in 0.05mL. As for sperm
      concentration, the average was 34.37 million/mL, with a decrease trend of 1.0
      million/mL. Progressive sperm motility showed an average of 47.27% and there was
      a decrease trend of 0.67%. Finally, sperm morphology presented an average of
      2.79% of normal spermatozoa, with a decrease trend of 0.33%. CONCLUSION : It can
      be noted that over the years, the sperm quality of men looking for assisted
      reproduction clinics has tended to decrease in macroscopic and microscopic
      parameters (volume, sperm concentration, motility and morphology).

PMID- 30118195
TI  - Effects of Moisture-Based Grain Boundary Passivation on Cell Performance and
      Ionic Migration in Organic-Inorganic Halide Perovskite Solar Cells.
AB  - Because of the polycrystalline nature, grain boundaries (GBs) in hybrid
      perovskite thin films play critical roles in determining the charge collection
      efficiency of perovskite solar cells (PSCs), material stability, and in
      particular the ion migration, considering their relatively soft ionic bonds with
      low formation energy. Different GB passivation methods are being studied, and
      introducing PbI2-rich phase at GBs in methylammonium lead iodide (MAPbI3) has
      been found to be useful. In this study, combining macroscale measurements with
      tip-based microscopic probing that includes scanning Kelvin probe microscopy for
      surface potential mapping and conductive atomic force microscopy for charge
      transport mapping, we revealed the effects of PbI2-rich phase at GBs, which was
      introduced in moisture-assisted synthesis of MAPbI3 thin films. It was found that
      PbI2 passivation of GBs could change the surface potential and charge carrier
      screening and significantly retard current conduction at the GB while enhancing
      conduction through the grain interior. Inhibition of ion migration at GBs, as
      well as enhanced PSC device performance, is reported.

PMID- 30118196
TI  - Fluorescence-Based Nano-Oxygen Particles for Spatiometric Monitoring of Cell
      Physiological Conditions.
AB  - Closed-loop artificial pancreas systems have recently been proposed as a solution
      for treating stage I diabetes by reproducing the function of the pancreas.
      However, there are many unresolved issues associated with their development,
      including monitoring and controlling oxygen, immune responses, and the
      optimization of glucose, all of which need to be monitored and controlled to
      produce an efficient and viable artificial organ that can become integrated in
      the patient and maintain homeostasis. This research focused on monitoring the
      oxygen concentration, specifically achieving this kinetically as the oxygen
      gradient in an artificial pancreas made of alginate spheres containing islet
      cells. Functional nanoparticles (NPs) for measuring the oxygen gradient in
      different hydrogel cellular environments using fluorescence-based (F) microscopy
      were developed and tested. By the ester bond, a linker Pluronic F127 was
      conjugated with a carboxylic acid-modified polystyrene NP (510 nm). A
      hydrophilic/hydrophobic interaction between the commercially available oxygen
      sensitive fluorophore and F127 results in fluorescence-based nano-oxygen
      particles (FNOPs). The in-house synthesized FNOP was calibrated inside
      electrosprayed alginate-filled hydrogels and demonstrated a good broad dynamic
      range (2.73-22.23) mg/L as well as a resolution of -0.01 mg/L with an accuracy of
      +/-4%. The calibrated FNOP was utilized for continuous measuring of the oxygen
      concentration gradient for cell lines RIN-m5F/HeLa for more than 5 days in
      alginate hydrogel spheres in vitro.

PMID- 30118197
TI  - Enhanced Therapeutic Effects of Mesenchymal Stem Cell-Derived Exosomes with an
      Injectable Hydrogel for Hindlimb Ischemia Treatment.
AB  - Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new
      candidates for cell-free treatment of various diseases. However, maintaining the
      retention and stability of exosomes over time in vivo after transplantation is a
      major challenge in the clinical application of MSC-derived exosomes. Here, we
      investigated if human placenta-derived MSC-derived exosomes incorporated with
      chitosan hydrogel could boost the retention and stability of exosomes and further
      enhance their therapeutic effects. Our results demonstrated that chitosan
      hydrogel notably increased the stability of proteins and microRNAs in exosomes,
      as well as augmented the retention of exosomes in vivo as confirmed by Gaussia
      luciferase imaging. In addition, we assessed endothelium-protective and
      proangiogenesis abilities of hydrogel-incorporated exosomes in vitro. Meanwhile,
      we evaluated the therapeutic function of hydrogel-incorporated exosomes in a
      murine model of hindlimb ischemia. Our data demonstrated that chitosan hydrogel
      could enhance the retention and stability of exosomes and further augment the
      therapeutic effects for hindlimb ischemia as revealed by firefly luciferase
      imaging of angiogenesis. The strategy used in this study may facilitate the
      development of easy and effective approaches for assessing and enhancing the
      therapeutic effects of stem cell-derived exosomes.

PMID- 30118198
TI  - pH- and Enzyme-Sensitive IR820-Paclitaxel Conjugate Self-Assembled Nanovehicles
      for Near-Infrared Fluorescence Imaging-Guided Chemo-Photothermal Therapy.
AB  - The short lifetime and easy quick elimination of the near-infrared (NIR) dye new
      indocyanine green (IR820) in the body restrict its practical application as a
      photothermal agent in cancer therapy. Meanwhile, the drawback of poor water
      solubility of the chemotherapeutic drug paclitaxel (PTX) largely restricts its
      clinical applications. Herein, we, for the first time, combined IR820 and PTX in
      an "all-in-one" fluorescence imaging-guided chemo-photothermal therapy (PTT)
      platform by a rational design of a novel pH- and enzyme-sensitive IR820-PTX
      conjugate assembly. Specifically, the IR820-PTX conjugate nanoparticles exhibit
      an extremely high therapeutic agent content (IR820 and PTX, 95.7%). Besides the
      good stability in bloodstream, the IR820-PTX nanoparticles can target tumors for
      high accumulation via the enhanced permeation and retention effect. Particularly,
      our IR820-PTX nanoparticles simultaneously solve the obstacles of PTX poor
      solubility and the short lifetime of IR820 for cancer therapy. The simultaneous
      release of the free drug and dye can efficiently kill tumor cells by the
      combination of PTT and chemotherapy via NIR irradiation. Furthermore, the
      combined therapy can be imaging-guided by measuring the NIR fluorescence imaging
      resulting from the IR820 component. Therefore, our rationally designed pH- and
      enzyme-sensitive IR820-PTX conjugate nanoparticles provide an alternative "all-in
      one" option for an efficient combinational dual-therapy and imaging.

PMID- 30118199
TI  - Effective Atmospheric-Pressure Plasma Treatment toward High-Performance Solution
      Processed Oxide Thin-Film Transistors.
AB  - Solution-processed oxide semiconductors (OSs) have attracted much attention
      because they can simply, quickly, and cheaply produce transparent channels on
      flexible substrates. However, despite such advantages, in the fabrication process
      of OS thin-film transistors (TFTs) using the solution process, it is a fatal
      problem that there are hardly any ways to simply and effectively control
      important TFT parameters, including the turn-on voltage ( Von) and on/off current
      ratio. For the practical application of solution-processed OS TFT, approaches to
      simply and effectively control the parameters are urgently required. Here, we
      newly propose an atmospheric-pressure plasma (APP) treatment that can simply and
      effectively control the electrical properties in solution-processed InO x TFTs.
      Through exposure of APP, we successfully realized the changes in important TFT
      parameters of solution-processed InO x TFT, Von from -11.4 to -1.9 V and the
      on/off current ratio from ~103 to ~106, which still keep up the high field-effect
      mobility (>20 cm2 V-1 s-1). On the basis of various analyses such as X-ray-based
      analysis and UV-visible spectroscopy, we identified that the APP treatment can
      effectively control oxygen vacancy and carrier concentration in solution
      processed OS.

PMID- 30118200
TI  - Rationally Developed Metallogelators Derived from Pyridyl Derivatives of NSAIDs
      Displaying Anti-Inflammatory and Anticancer Activities.
AB  - Metal-ligand coordination involving hydrogen-bond-functionalized ligands was
      employed rationally to get an easy access to a series of metallogelators derived
      from 3-pyridyl derivatives of nonsteroidal anti-inflammatory drugs [e.g.,
      ibuprofen, sulindac, and flurbiprofen designated as 3-pyIBU, 3-pySUL, and 3
      pyFLR, respectively] and biogenic metal centers [Zn(II), Cu(II), Mn(II), and
      Ag(I)]. A total of 13 metallogels (MG1-MG13) were obtained by allowing the
      ligands and the metal salts to react in dimethyl sulfoxide (DMSO)/water at room
      temperature. A slightly different solvent system (DMSO/water/MeOH) afforded four
      crystalline coordination complexes of 3-pyIBU, namely, [{Cu(3
      pyIBU)4(DMSO)2}(NO3)2] (CC1), [{Ag(3-pyIBU)2}(BF4)] (CC2), [{Ag(3-pyIBU)2}(ClO4)]
      (CC3), and [{Cu(3-pyIBU)4(CH3OH)2}(OTf)] (CC4), which were fully characterized by
      single-crystal X-ray diffraction. However, none of these coordination complexes
      produced metallogels-the results corroborated well with the rationale, based on
      which the metallogelators were obtained. Two selected metallogels (MG3 and MG9)
      could be leached out from the corresponding metallogels to the bulk solvent to
      the extent of 51 and 59%, respectively after 24 h of incubation at 37  degrees C,
      indicating their plausible use in topical application. Moreover, one of the
      selected metallogelators, i.e., MG9, displayed anti-inflammatory response and was
      able to inhibit the migration of highly aggressive human breast cancer cells MDA
      MB-231, suggesting its plausible use as anticancer agent.

PMID- 30118201
TI  - Enhancing Efficiency and Stability of Perovskite Solar Cells via a Self-Assembled
      Dopamine Interfacial Layer.
AB  - Interfacial engineering is a simple and effective strategy that can improve the
      photovoltaic performance in organic-inorganic perovskite solar cells (PSCs).
      Herein, a dopamine (DA) self-assembled monolayer (SAM) was introduced on the top
      of the SnO2 electron transporting layer (ETL) to modify the SnO2/perovskite
      interface. The processing temperature of the present devices is around 150 
      degrees C, and the power conversion efficiency of the PSCs was significantly
      improved to 16.65% compared to that of the device without modification (14.05%).
      Such enhancement in efficiency is mainly attributed to the improved quality of
      perovskite films by improving the affinity of the SnO2 ETL, thus leading to
      better carrier transport and low charge recombination at the SnO2/perovskite
      interface. Moreover, the modified device by the DA SAM exhibited enhanced
      stability compared to the device without modification. Our results suggest that
      the introduction of the DA SAM on the ETL/perovskite interface is a promising
      method for highly efficient and stable PSCs.

PMID- 30118202
TI  - alpha-Fe2O3 Nanodisk/Bacterial Cellulose Hybrid Membranes as High-Performance
      Sulfate-Radical-Based Visible Light Photocatalysts under Stirring/Flowing States.
AB  - High activity and long-term stability are particularly important for
      peroxymonosulfate (PMS)-based degradation processes in wastewater treatment,
      especially under a flowing state. However, if the highly active nanomaterials are
      in a powder form, they could disperse well in water but would not be convenient
      for application under varied flow rates. A metal oxide/bacterial cellulose hybrid
      membrane fixed in a flowing bed is expected to solve these problems. Herein,
      alpha-Fe2O3 nanodisk/bacterial cellulose hybrid membranes as high-performance
      sulfate-radical-based visible light photocatalysts are synthesized for the first
      time. The bacterial cellulose with excellent mechanical stability and film
      forming feature not only benefits the formation of a stable membrane to avoid the
      separation and recycling problems but also helps disperse and accommodate alpha
      Fe2O3 nanodisks and thus enhances the visible light absorption performances,
      leading to an excellent PMS-based visible light degradation efficiency under both
      stirring and flowing states. Particularly, the optimized hybrid membrane
      photocatalyzes both cationic and anionic organic dyes under a flowing bed state
      for at least 84 h with the catalytic efficiency up to 100% and can be easily
      separated after the reaction, confirming its remarkable catalytic performance and
      long-term stability. Even under varied flow rates during the continuous process,
      it efficiently degrades rhodamine B and orange II from 3 to 16 mL h-1. When the
      flow rate goes back from high to low, the hybrid membrane quickly recovers its
      original performance, demonstrating the high activity and stability of the alpha
      Fe2O3/bacterial cellulose membrane.

PMID- 30118203
TI  - Recent Developments in the Scope, Practicality, and Mechanistic Understanding of
      Enantioselective Hydroformylation.
AB  - In the nearly 80 years since catalytic hydroformylation was first reported,
      hundreds of billions of pounds of aldehyde have been produced by this atom
      efficient one-carbon homologation of alkenes in the presence of H2 and CO.
      Despite the economy and demonstrated scalability of hydroformylation, the
      enantioselective process (asymmetric hydroformylation, AHF) currently does not
      contribute significantly to the production of chiral aldehydes and their
      derivatives. Current impediments to practical application of AHF include low
      diversity of chiral ligands that provide effective rates and selectivities,
      limited exploration of substrate scope, few demonstrations of efficient flow
      reactor processes, and incomplete mechanistic understanding of the factors that
      control reaction selectivity and rate. This Account summarizes developments in
      ligand design, substrate scope, reactor technology, and mechanistic understanding
      that advance AHF toward practical and atom-efficient production of chiral alpha
      stereogenic aldehydes. Initial applications of AHF were limited to activated
      terminal alkenes such as styrene, but recent developments enable high selectivity
      for unactivated olefins and more complex substrates such as 1,1'- and 1,2
      disubstituted alkenes. Expanded substrate scope primarily results from new chiral
      phosphine ligands, especially phospholanes and bisdiazaphospholanes (BDPs). These
      ligands are now more accessible due to improved synthesis and resolution
      procedures. One of the virtues of diazaphospholanes is the relative ease of
      derivatization, including attachment to heterogeneous supports. Hydroformylation
      involves toxic and flammable reactants, a serious concern in pharmaceutical
      production facilities. Flow reactors offer many process benefits for handling
      dangerous reagents and for systematically moving from research to production
      scales. New approaches to achieving good gas-liquid mixing in flow reactors have
      been demonstrated with BDP-derived catalyst systems and lend assurance that AHF
      can be practically implemented by the pharmaceutical and fine chemical
      industries. To date, progress in AHF has been empirically driven, because
      hydroformylation is a complex, multistep process for which the origins of chemo-,
      regio-, and enantioselectivity are difficult to elucidate. Mechanistic complexity
      arises from three concurrent catalytic cycles (linear and two diastereomeric
      branched paths), significant pooling of catalyst as off-cycle species, and
      multiple elementary steps that are kinetically competitive. Addressing such
      complexity requires new approaches to collecting kinetic and extra-kinetic
      information and analyzing these data. In this Account, we describe our group's
      progress toward understanding the complex kinetics and mechanism of AHF as
      catalyzed by rhodium bis(diazaphospholane) catalysts. Our strategy features both
      "outside-in" (i.e., monitoring catalytic rates and selectivities as a function of
      reactant concentration and temperature) and "inside-out" (i.e., building kinetic
      models based on the rates of component steps of the catalytic reaction)
      approaches. These studies include isotopic labeling, interception and
      characterization of catalytic intermediates using NMR techniques, multinuclear
      high-pressure NMR spectroscopy, and sophisticated kinetic modeling. Such broad
      based approaches illuminate the kinetic and mechanistic origins of selectivity
      and activity of AHF and the elucidation of important principles that apply to all
      catalytic reactions.

PMID- 30118204
TI  - Orientation-Dependent Optical Magnetoelectric Effect in Patterned
      BaTiO3/La0.67Sr0.33MnO3 Heterostructures.
AB  - The optical magnetoelectric effect has been widely investigated, but obtaining
      the large and tunable optical magnetoelectric effect at room temperature is still
      a big challenge. We here design ferroelectric/ferromagnetic heterostructures with
      various orientations, which are composed of titanate BaTiO3 and manganese oxide
      La0.67Sr0.33MnO3. This artificial bilayer structure presents room-temperature
      ferroelectric and ferromagnetic properties. After patterning a 4 MUm grating
      structure on the bilayer thin film, the optical magnetoelectric effect for near
      infrared light is investigated systematically through the Bragg diffraction
      method. The relative change of diffracted light intensity of the order n = 1 has
      a strong dependence on the magnetization and polarization of the thin films,
      whether the superlattice is irradiated in reflection or transmission geometries.
      For (100)- and (111)-oriented samples, both show the room-temperature optical
      magnetoelectric effect, while the (111)-oriented thin film has a stronger optical
      magnetoelectric effect. These results pave the way for designing next-generation
      optical magnetoelectric devices based on the ferroelectric/ferromagnetic
      structure.

PMID- 30118205
TI  - Transparent Antiradiative Ferroelectric Heterostructure Based on Flexible Oxide
      Heteroepitaxy.
AB  - In the era of Internet of Things, the demand for flexible and transparent
      electronic devices has shifted to the forefront of materials science research.
      However, the radiation damage to key performance of transparent devices under
      radiative environment remains as a critical issue. Here, we present a promising
      technology for nonvolatile transparent electronic devices based on flexible oxide
      heteroepitaxy. A direct fabrication of epitaxial lead lanthanum zirconate
      titanate on transparent flexible mica substrate with indium tin oxide electrodes
      is presented. The transparent flexible ferroelectric heterostructures not only
      retain their superior performance, thermal stability, reliability, and mechanical
      durability, but also exhibit remarkably robust properties against to a strong
      radiation exposure. Our study demonstrates an extraordinary concept to realize
      transparent flexible nonvolatile electronic devices for the design and
      development of next-generation smart devices with potential application in
      electronics, automotive, aerospace, and nuclear systems.

PMID- 30118206
TI  - Self-Inhibitory Electron Transfer of the Co(III)/Co(II)-Complex Redox Couple at
      Pristine Carbon Electrode.
AB  - Applications of conducting carbon materials for highly efficient electrochemical
      energy devices require a greater fundamental understanding of heterogeneous
      electron-transfer (ET) mechanisms. This task, however, is highly challenging
      experimentally, because an adsorbing carbon surface may easily conceal its
      intrinsic reactivity through adventitious contamination. Herein, we employ
      nanoscale scanning electrochemical microscopy (SECM) and cyclic voltammetry to
      gain new insights into the interplay between heterogeneous ET and adsorption of a
      Co(III)/Co(II)-complex redox couple at the contamination-free surface of electron
      beam-deposited carbon (eC). Specifically, we investigate the redox couple of
      tris(1,10-phenanthroline)cobalt(II), Co(phen)32+, as a promising mediator for dye
      sensitized solar cells and redox flow batteries. A pristine eC surface overlaid
      with KCl is prepared in vacuum, protected from contamination in air, and exposed
      to an ultrapure aqueous solution of Co(phen)32+ by the dissolution of the
      protective KCl layer. We employ SECM-based nanogap voltammetry to quantitatively
      demonstrate that Co(phen)32+ is adsorbed on the pristine eC surface to
      electrostatically self-inhibit outer-sphere ET of nonadsorbed Co(phen)33+ and
      Co(phen)32+. Strong electrostatic repulsion among Co(phen)32+ adsorbates is also
      demonstrated by SECM-based nanogap voltammetry and cyclic voltammetry.
      Quantitatively, self-inhibitory ET is characterized by a linear decrease in the
      standard rate constant of Co(phen)32+ oxidation with a higher surface
      concentration of Co(phen)32+ at the formal potential. This unique relationship is
      consistent not with the Frumkin model of double layer effects, but with the
      Amatore model of partially blocked electrodes as extended for self-inhibitory ET.
      Significantly, the complicated coupling of electron transfer and surface
      adsorption is resolved by combining nanoscale and macroscale voltammetric
      methods.

PMID- 30118207
TI  - Electrochemical Detection of Viable Bacterial Cells Using a Tetrazolium Salt.
AB  - In this study, electrochemical detection of viable bacterial cells was performed
      using a tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
      bromide (MTT), which was converted to an insoluble and redox active formazan
      compound in viable microbial cells. The insolubility of this formazan was
      effectively exploited as a surface-confined redox event. An indium-tin-oxide
      electrode was applied to a microbial suspension that had been incubated with MTT
      and was heated to dry for the extraction and adsorption of formazan. Drying led
      to the appearance of a distinctive voltammetric oxidation peak at +0.1 V vs
      Ag|AgCl, the magnitude of which was successfully correlated to the number of
      viable microbes in the suspension. Thus, the electrochemical detection of
      formazan was effectively coupled with the thermal lysis of microbes. It is also
      noteworthy that this lysis-adsorption technique was highly selective to the
      hydrophobic formazan molecule due to the removal of hydrophilic cell components
      during equilibration in a phosphate buffer before voltammetric measurement. This
      technique was capable of detecting microbes above 2.8 * 101 CFU mL-1 and required
      only a 1 h incubation. The results of this study indicate that the sensitivity of
      the present technique is up to 10 000-fold higher than that of MTT colorimetry.
      The higher sensitivity was mainly ascribed to the concentration of the
      microbially produced formazan on the electrode by thorough desiccation of the
      bacterial suspension.

PMID- 30118208
TI  - Scanning Plasmonic Color Display.
AB  - Control over plasmonic colors on the nanoscale is of great interest for high
      resolution display, imaging, and information encryption applications. However, so
      far, very limited schemes have been attempted for dynamic plasmonic color
      generation. In this paper, we demonstrate a scanning plasmonic color generation
      scheme, in which subwavelength plasmonic pixels can be laterally switched on/off
      through directional hydrogenation/dehydrogenation of a magnesium screen. We show
      several dynamic plasmonic color displays with different scanning functions by
      varying the number and geometries of the palladium gates, where hydrogen enters
      the scanning screens. In particular, we employ the scanning effects to create a
      dynamic plasmonic quick response code. The information cannot be decrypted by
      varying the polarization states of light or by accessing the physical features.
      Rather, it can only be read out using hydrogen as a decoding key. Our work
      advances the established design concepts for plasmonic color printing and
      provides insights into the development of optical information storage and
      anticounterfeiting features.

PMID- 30118209
TI  - Characterization of SPR994, an Orally Available Carbapenem, with Activity
      Comparable to Intravenously Administered Carbapenems.
AB  - Carbapenems are potent antibacterials with broad-spectrum activity. However, poor
      oral absorption generally confines this important drug class to in-hospital use
      by intravenous (IV) administration. The continued rise in drug resistant
      pathogens creates a need for alternative oral therapies with broad-spectrum
      activity. SPR994 is a novel formulation of the orally bioavailable pivoxil
      prodrug of SPR859 (tebipenem) and is being developed as the first oral carbapenem
      for treatment of complicated urinary tract infections (cUTIs) in adults. Herein,
      we describe characteristics beneficial to oral administration and compare the in
      vitro and in vivo activity of SPR859 or SPR994 with IV carbapenems.

PMID- 30118210
TI  - Elucidating the Reaction Mechanisms between Triazine and Hydrogen Sulfide with pH
      Variation Using Mass Spectrometry.
AB  - Triazine is one of the most economical and effective scavengers for hydrogen
      sulfide (H2S) removal, but the reaction mechanisms between triazine and H2S with
      pH variation in solution are still poorly understood. Herein, we show that the
      reaction process can be directly probed by means of paper spray mass
      spectrometry, in which an aprotic solvent (e.g., acetonitrile) is more favorable
      to the observation of reaction intermediates than a protic solvent (e.g.,
      methanol), because of hydrogen bond interaction. Varying the pH of the reaction
      leads to completely different reaction pathways. With the pH in the range of 5.58
      to 7.73, the major product was thiadiazine. With a pH of 3.02-3.69, thiadiazine
      is converted to 2-(5-(2-hydroxyethyl)-1,3,5-thiadiazinan-3-yl)acetaldehyde, which
      differs from the traditional pathway of analogous reactions. However, as ammonia
      was added into the reaction and the pH was adjusted to the range 8.45-9.43,
      triazine readily undergoes hydrolysis, and the formed intermediate reacts with
      ammonia and formaldehyde generated in situ from triazine to produce 1-(2
      hydroxyethyl)-3,5,7-triaza-1-azoniatricyclo [3.3.1.13,7]decane (HTAD). Further
      increasing the pH up to 10.27-11.21 leads to the decomposition of HTAD. Based on
      the experimental observation and evidence from high-resolution and tandem mass
      spectrometry, we propose the plausible reaction mechanisms between triazine and
      H2S, as well as the derived reaction from triazine under different pH conditions.

PMID- 30118211
TI  - All-Solution-Processed Thermally and Chemically Stable Copper-Nickel Core-Shell
      Nanowire-Based Composite Window Electrodes for Perovskite Solar Cells.
AB  - Organic-inorganic hybrid perovskite solar cells (PSCs) have recently attracted
      tremendous attention because of their excellent efficiency and the advantage of a
      low-cost fabrication process. As a transparent electrode for PSCs, the
      application of copper nanowire (CuNW)-network was limited because of its
      thermal/chemical instability, despite its advantages in terms of high
      optical/electrical properties and low-cost production. Here, the copper-nickel
      core-shell nanowire (Cu@Ni NW)-based composite electrode is proposed as a bottom
      window electrode for PSCs, without the involvement of a high-cost precious metal
      and vacuum process. The dense and uniform Ni protective shell for CuNWs is
      attainable by simple electroless plating, and the resulting Cu@Ni NWs exhibit
      outstanding chemical stability as well as thermal stability compared with bare
      CuNWs. When the Ni layer with the optimal thickness is introduced, the Cu@Ni NW
      electrode shows a high transmittance of 80.5% AVT at 400-800 nm, and a sheet
      resistance of 49.3 +/- 5 Omega sq-1. Using the highly stable Cu@Ni NWs, the
      composite electrode structure is fabricated with sol-gel-derived Al-doped zinc
      oxide (AZO) over-layer for better charge collection and additional protection
      against iodine ions from the perovskite. The PSCs fabricated with AZO/Cu@Ni NW
      based composite electrode demonstrate a power conversion efficiency (PCE) of
      12.2% and excellent long-term stability maintaining 91% of initial PCE after
      being stored for 500 h at room temperature. Experimental results demonstrate the
      potential of highly stable Cu@Ni NW-based electrodes as the cost-effective
      alternative transparent electrode, which can facilitate the commercialization of
      PSCs.

PMID- 30118212
TI  - Use-Phase Drives Lithium-Ion Battery Life Cycle Environmental Impacts When Used
      for Frequency Regulation.
AB  - Battery storage systems are attractive alternatives to conventional generators
      for frequency regulation due to their fast response time, high cycle efficiency,
      flexible scale, and decreasing cost. However, their implementation does not
      consistently reduce environmental impacts. To assess these impacts, we employed a
      life cycle assessment (LCA) framework. Our framework couples cradle-to-gate and
      end-of-life LCA data on lithium-ion batteries with a unit commitment and dispatch
      model. The model is run on a 9-bus power system with energy storage used for
      frequency regulation. The addition of energy storage changes generator commitment
      and dispatch, causing changes in the quantities of each fuel type consumed. This
      results in increased environmental impacts in most scenarios. The impacts caused
      by the changes in the power system operation (i.e., use-phase impacts) outweigh
      upstream and end-of-life impacts in the majority of scenarios analyzed with the
      magnitude most influenced by electricity mix and fuel price. Of parameters
      specific to the battery, round trip efficiency has the greatest effect.

PMID- 30118213
TI  - Methane Production and Conductive Materials: A Critical Review.
AB  - Conductive materials (CM) have been extensively reported to enhance methane
      production in anaerobic digestion processes. The occurrence of direct
      interspecies electron transfer (DIET) in microbial communities, as an alternative
      or complementary to indirect electron transfer (via hydrogen or formate), is the
      main explanation given to justify the improvement of methane production. Not
      disregarding that DIET can be promoted in the presence of certain CM, it surely
      does not explain all the reported observations. In fact, in methanogenic
      environments DIET was only unequivocally demonstrated in cocultures of Geobacter
      metallireducens with Methanosaeta harundinacea or Methanosarcina barkeri and
      frequently Geobacter sp. are not detected in improved methane production driven
      systems. Furthermore, conductive carbon nanotubes were shown to accelerate the
      activity of methanogens growing in pure cultures, where DIET is not expected to
      occur, and hydrogenotrophic activity is ubiquitous in full-scale anaerobic
      digesters treating for example brewery wastewaters, indicating that interspecies
      hydrogen transfer is an important electron transfer mechanism in those systems.
      This paper presents an overview of the effect of several iron-based and carbon
      based CM in bioengineered systems, focusing on the improvement in methane
      production and in microbial communities' changes. Control assays, as fundamental
      elements to support major conclusions in reported experiments, are critically
      revised and discussed.

PMID- 30118214
TI  - Lysosome-Targeted Chemotherapeutics: Half-Sandwich Ruthenium(II) Complexes That
      Are Selectively Toxic to Cancer Cells.
AB  - Poor selectivity between cancer cells and normal cells is one of the major
      limitations of cancer chemotherapy. Lysosome-targeted ruthenium-based complexes
      target tumor cells selectively, only displaying rather weak cytotoxicity or
      inactivity toward normal cells. Confocal microscopy was employed for the first
      time to determine the cellular localization of the half-sandwich Ru complex.

PMID- 30118215
TI  - Emissions, Transport, and Fate of Emerging Per- and Polyfluoroalkyl Substances
      from One of the Major Fluoropolymer Manufacturing Facilities in China.
AB  - Fluoropolymer manufacturing is a major historical source of perfluorooctanoic
      acid (PFOA) on a global scale, but little is known about the emissions,
      transport, and fate of emerging per- and polyfluoroalkyl substances (PFASs).
      Here, we performed a comprehensive spatial trend and interyear comparison of
      surface water and sediment samples from the Xiaoqing River, which receives water
      discharge from one of the major fluoropolymer manufacturing facilities in China.
      A suspect screening identified 42 chemical formulas, including the tetramer acid
      of hexafluoropropylene oxide (HFPO-TeA) and numerous tentatively detected isomers
      of C9-C14 per- or polyfluoroalkyl ether carboxylic acids (PFECAs). As revealed by
      the spatial trends and peak area-based sediment-water distribution coefficients,
      emerging PFASs with 3-9 perfluorinated carbons were transported unimpededly with
      the bulk water flow having no measurable degradation. Emerging PFASs with >9
      perfluorinated carbons displayed more rapidly decreasing spatial trends than
      shorter-chain homologues in surface water due to increasing sedimentation rates.
      The presence of HFPO oligomers, monoether PFECAs, monohydrogen-substituted
      perfluoroalkyl carboxylic acids (PFCAs) and monochlorine-substituted PFCAs could
      partly be explained by the active use of polymerization aids or the impurities
      therein. However, further research is encouraged to better characterize the
      emissions of low-molecular-weight PFASs from fluoropolymers throughout their life
      cycle.

PMID- 30118216
TI  - Potential Toxicity of Dissolved Metal Mixtures (Cd, Cu, Pb, Zn) to Early Life
      Stage White Sturgeon ( Acipenser transmontanus) in the Upper Columbia River,
      Washington, United States.
AB  - The Upper Columbia River (UCR) received historical releases of smelter waste
      resulting in elevated metal concentrations in downstream sediments. Newly hatched
      white sturgeon hide within the rocky substrate at the sediment-water interface in
      the UCR for a few weeks before swim-up. Hiding behavior could expose them to
      metal contaminants, and metal toxicity could contribute to population declines in
      white sturgeon over the past 50 years. This study evaluates whether there is a
      link between the toxicity of dissolved metals across the sediment-water interface
      in the UCR and the survival of early life stage (ELS) white sturgeon. Toxicity of
      dissolved metal mixtures is evaluated using a combination of previously collected
      laboratory and field data and recently developed metal mixture toxicity models.
      The laboratory data consist of individual metal (Cd, Cu, Pb, and Zn) toxicity
      studies with ELS white sturgeon. The field data include the chemical composition
      of surface and pore water samples that were collected across the sediment-water
      interface in the UCR. These data are used in three metal accumulation and two
      response models. All models predict low toxicity in surface water, whereas
      effects concentrations greater than 20% are predicted for 60-72% of shallow pore
      water samples. The flux of dissolved metals, particularly Cu, from shallow pore
      water to surface water likely exposes prime ELS sturgeon habitat to toxic
      conditions.

PMID- 30118217
TI  - Biosynthesis of the Thiopeptins and Identification of an F420H2-Dependent
      Dehydropiperidine Reductase.
AB  - Thiopeptins are highly decorated thiopeptide antibiotics similar in structure to
      thiostrepton A and harbor two unusual features. All thiopeptins contain a
      thioamide, a rare moiety among natural products, and a subset of thiopeptins
      present with a piperidine in the core macrocycle rather than the more oxidated
      dehydropiperidine or pyridine rings typically observed in the thiopeptides. Here,
      we report the identification of the thiopeptin biosynthetic gene ( tpn) cluster
      in Streptomyces tateyamensis and the gene product, TpnL, which shows sequence
      similarity to (deaza)flavin-dependent oxidoreductases. Heterologous expression of
      TpnL in the thiostrepton A producer Streptomyces laurentii led to the production
      of a piperidine-containing analogue. Binding studies revealed that TpnL
      preferentially binds the deazaflavin cofactor coenzyme F420, and in vitro
      reconstitution of TpnL activity confirmed that this enzyme is an F420H2-dependent
      dehydropiperidine reductase. The identification of TpnL and its activity
      establishes the basis for the piperidine-containing series a thiopeptides, one of
      the five main structural groups of this diverse family of antibiotics.

PMID- 30118218
TI  - Polyanionic Gold-Tin Bonding and Crystal Structure Preference in REAu1.5Sn0.5 (RE
      = La, Ce, Pr, Nd).
AB  - During a systematic search of the RE-Au-Sn (RE = La, Ce, Pr, Nd) ternary phase
      space, a series of compounds with the general formula REAu1.5Sn0.5 have been
      identified. These phases can be synthesized by arc melting the elemental metals,
      followed by annealing. The crystal structures were solved using single-crystal X
      ray diffraction, with the composition confirmed by energy-dispersive X-ray
      spectroscopy. All four compounds crystallize in orthorhombic space group Imma
      with the CeCu2-type structure. Most notable in these compounds is the polyanionic
      backbone composed of a single statistically mixed Au/Sn position, which creates a
      puckered hexagonal bonding network separated by the rare-earth atoms. Electronic
      structure calculations indicate that the Au 5d bands are dominant in the density
      of states, while the crystal orbital Hamilton population (-COHP) curves
      demonstrate Au-Au and Au-Sn interactions, which stabilize the crystal structure.
      Likewise, a qualitative electron localization function analysis supports the
      existence of a polyanionic network, and a Bader charge analysis implies anionic
      character on Au and Sn. The preference for these compounds to adopt the simple
      CeCu2-type structure is also determined using density functional theory
      calculations and compared to related compounds to establish a better picture of
      the unusual behavior of Au in polar intermetallic compounds.

PMID- 30118220
TI  - How Reactive are Druggable Cysteines in Protein Kinases?
AB  - Targeted covalent inhibitors (TCIs) have been successfully developed as high
      affinity and selective inhibitors of enzymes of the protein kinase family. These
      drugs typically act by undergoing an electrophilic addition with an active-site
      cysteine residue, so design of a TCI begins with the identification of a
      "druggable" cysteine. These electrophilic additions generally require
      deprotonation of the thiol to form a reactive anionic thiolate, so the acidity of
      the residue is a critical factor. Few experimental measurements of the p Ka's of
      druggable cysteines have been reported, so computational prediction could prove
      to be very important in selecting reactive cysteine targets. Here we report the
      computed p Ka's of druggable cysteines in selected protein kinases that are of
      clinical relevance for targeted therapies. The p Ka's of the cysteines were
      calculated using advanced computational methods based on all-atom replica
      exchange thermodynamic integration molecular dynamics simulations in explicit
      solvent. We found that the acidities of druggable cysteines within protein
      kinases are diverse and elevated, indicating enormous differences in their
      reactivity. Constant-pH molecular dynamics simulations were also performed on
      selected protein kinases, and the results confirmed this varied range in the
      acidities of druggable cysteines. Many of these active-site cysteines have low
      exposure to solvent molecules, elevating their p Ka values. Electrostatic
      interactions with nearby anionic residues also elevate the p Ka's of cysteine
      residues in the active site. The results suggest that some cysteine residues
      within kinase binding sites will be slow to react with a TCI because of their low
      acidity. Several oncogenic kinase mutations were also modeled and found to have p
      Ka's similar to that of the wild-type kinase.

PMID- 30118219
TI  - Cell Penetration Profiling Using the Chloroalkane Penetration Assay.
AB  - Biotherapeutics are a promising class of molecules in drug discovery, but they
      are often limited to extracellular targets due to their poor cell penetration.
      High-throughput cell penetration assays are required for the optimization of
      biotherapeutics for enhanced cell penetration. We developed a HaloTag-based assay
      called the chloroalkane penetration assay (CAPA), which is quantitative, high
      throughput, and compartment-specific. We demonstrate the ability of CAPA to
      profile extent of cytosolic penetration with respect to concentration, presence
      of serum, temperature, and time. We also used CAPA to investigate structure
      penetration relationships for bioactive stapled peptides and peptides fused to
      cell-penetrating sequences. CAPA is not only limited to measuring cytosolic
      penetration. Using a cell line where HaloTag is localized to the nucleus, we show
      quantitative measurement of nuclear penetration. Going forward, CAPA will be a
      valuable method for measuring and optimizing the cell penetration of
      biotherapeutics.

PMID- 30118221
TI  - Nearly Pure Red Color Upconversion Luminescence of Ln-Doped Sc2O3 with Unexpected
      RE-MOFs Molecular Alloys as Precursor.
AB  - Unexpected Sc/Ln codoped rare earth metal-organic frameworks (RE-MOFs) molecular
      alloys (MAs) based on an oxalic acid ligands were obtained. Calcination of the RE
      MOFs MAs gave the corresponding codoped rare earth oxides a strong and nearly
      pure red color upconversion luminescence. It allows the resulting lanthanide ion
      (Ln3+) doped upconversion materials a wide range of applications from optical
      communications to disease diagnosis. Moreover, the pyrolysis RE-MOFs MAs
      precursor has demonstrated to be an effective preparation method for a uniform Ln
      doped Sc2O3 system.

PMID- 30118222
TI  - Catalytically Synthesized Prussian Blue Nanoparticles Defeating Natural Enzyme
      Peroxidase.
AB  - We synthesized Prussian Blue (PB) nanoparticles through catalytic reaction
      involving hydrogen peroxide (H2O2) activation. The resulting nanoparticles
      display the size-dependent catalytic rate constants in H2O2 reduction, which are
      significantly improved compared to natural enzyme peroxidase: for PB
      nanoparticles 200 nm in diameter, the turnover number is 300 times higher; for
      570 nm diameter nanoparticles, it is 4 orders of magnitude higher. Comparing to
      the known peroxidase-like nanozymes, the advantages of the reported PB
      nanoparticles are their true enzymatic properties: (1) enzymatic specificity (an
      absence of oxidase-like activity) and (2) an ability to operate in physiological
      solutions. The ultrahigh activity and enzymatic specificity of the catalytically
      synthesized PB nanoparticles together with high stability and low cost, obviously
      peculiar to noble metal free inorganic materials, would allow the substitution of
      natural and recombinant peroxidases in biotechnology and analytical sciences.

PMID- 30118223
TI  - Stable Supersupertetrahedron with Infinite Order via the Assembly of
      Supertetrahedral T4 Zinc-Indium Sulfide Clusters.
AB  - A new family member of T p, q-based hierarchical chalcogenide architecture was
      created by assembling regular T4-ZnInS clusters into a periodically "hollowed
      out" cubic ZnS-type structure framework (T4,infinity) via the cross-linker of the
      tetracoordinated corner MU4-S2-. Ion-exchange and CO2 adsorption experiments
      suggest that such a structure with a corner MU4-S2- linker has structural
      stability superior to those of previously reported chalcogenide open frameworks
      composed of the same T4-ZnInS clusters with a bicoordinated (MU2-S2-) or a
      tricoordinated (MU3-S2-) cross-linker. Importantly, this case further
      demonstrates the feasibility of systematically engineering stable porous
      crystalline chalcogenide frameworks by a "hollow-out" strategy.

PMID- 30118224
TI  - Histone Deacetylase 6-Selective Inhibitors and the Influence of Capping Groups on
      Hydroxamate-Zinc Denticity.
AB  - Four crystal structures are presented of histone deacetylase 6 (HDAC6) complexes
      with para-substituted phenylhydromaxamate inhibitors, including bulky peptoids.
      These structures provide insight regarding the design of capping groups that
      confer selectivity for binding to HDAC6, specifically with regard to interactions
      in a pocket formed by the L1 loop. Capping group interactions may also influence
      hydroxamate-Zn2+ coordination with monodentate or bidentate geometry.

PMID- 30118225
TI  - Microviscosity in E. coli Cells from Time-Resolved Linear Dichroism Measurements.
AB  - A protein's folding or function depends on its mobility through the viscous
      environment that is defined by the presence of macromolecules throughout the
      cell. The relevant parameter for this mobility is microviscosity-the viscosity on
      a time and distance scale that is important for protein folding/function
      movements. A quasi-null, ultrasensitive time-resolved linear dichroism (TRLD)
      spectroscopy is proving to be a useful tool for measurements of viscosity on this
      scale, with previous in vitro studies reporting on the microviscosities of
      crowded environments mimicked by high concentrations of different macromolecules.
      This study reports the microviscosity experienced by myoglobin in the E. coli
      cell's heterogeneous cytoplasm by using TRLD to measure rotational diffusion
      times. The results show that photolyzed deoxyMb ensembles randomize through
      environment-dependent rotational diffusion with a lifetime of 34 +/- 6 ns. This
      value corresponds to a microviscosity of 2.82 +/- 0.42 cP, which is consistent
      with previous reports of cytoplasmic viscosity in E. coli. The results of these
      TRLD studies in E. coli (1) provide a measurement of myoglobin mobility in the
      cytoplasm, (2) taken together with in vitro TRLD studies yield new insights into
      the nature of the cytoplasmic environment in cells, and (3) demonstrate the
      feasibility of TRLD as a probe of intracellular viscosity.

PMID- 30118226
TI  - Effect of Surfactants on Surface-Induced Denaturation of Proteins: Evidence of an
      Orientation-Dependent Mechanism.
AB  - When proteins bind to interfaces, the resulting changes in protein structure can
      lead to loss of protein function. We investigate the mechanism by which
      surfactant molecules can counteract surface-induced protein denaturation through
      a detailed study of the stability of the GB1 peptide at the air-water, ice-water,
      and silica-water interfaces using molecular dynamics simulations coupled with
      metadynamics. Our simulations reveal that the air-water interface and, to a
      lesser extent, the ice-water interface destabilize the protein by direct
      interactions between the protein and surface that disrupt the hydrophobic core of
      the protein, while the weakly interacting silica surface stabilizes the protein
      through confinement effects. Addition of the surfactant Tween 80 leads to
      stabilization of the protein at the air-water and ice-water surfaces and mild
      destabilization at the water-silica interface. We show that the amphiphilic
      nature of the surfactant is key to its stabilizing/destabilizing effect, with an
      orientation-dependent mechanism in which the protein is stabilized when the
      hydrophilic heads of the surfactant point toward the protein.

PMID- 30118227
TI  - Investigation of Li+ Cation Coordination and Transportation, by Molecular
      Modeling and NMR Studies, in a LiNTf2-Doped Ionic Liquid-Vinylene Carbonate
      Mixture.
AB  - To increase the safety and stability of lithium-ion batteries, the development of
      electrolytes based on ionic liquids (ILs) has gained a lot of attention in recent
      years. However, with graphite electrodes, neat ILs afford weak cycling
      performance in the absence of organic additives (e.g., vinylene carbonate, VC).
      The potential formation of a [Li+]-OVC interaction/coordination could have a
      major influence on the observed electrochemical behavior of Li-ion batteries. On
      a specific electrolyte, 1-hexyl-3-methylimidazolium
      bis(trifluoromethanesulfonyl)imide [C1C6Im][NTf2] in association with Li[NTf2] (1
      mol L-1) and VC, we performed NOESY, {1H-7Li} HOESY correlations, and pulsed
      field gradient spin-echo NMR measurements, combined with molecular dynamics
      simulations to determine whether such an interaction/coordination between VC and
      Li+ ions is noticeable. {7Li-1H} HOESY experiment shows the vicinity of VC with
      [Li+] cation, and strong correlations and association between [Li+] and VC are
      observed in intense first peaks in radial distribution functions and quantified
      by the coordination numbers in the first solvation shell between [Li+] and the
      carbonyl oxygen atom of VC.

PMID- 30118228
TI  - Ultrasharp h-BN Nanocones and the Origin of Their High Mechanical Stiffness and
      Large Dipole Moment.
AB  - We report on experimental synthesis and theoretical studies of ultrasharp BN
      nanocones. Using scanning and transmission electron microscopy, the cone-like
      morphology of synthesized products was confirmed. Theoretical analysis of the
      dipole moment nature in h-BN nanocones reveals that the moment has contributions
      from the polarity of B-N bonds and electronic flexoelectric effect associated
      with a curved h-BN lattice. The latter phenomenon is predicted on the basis of
      the extension of the theory of flexoelectric effects in the h-BN lattice through
      establishing universality of the linear dependence of flexoelectric dipole
      moments on local curvature in various nano- h-BN networks (nanotubes and
      fullerenes). Our study of the atomic structure response and its polarization
      under deformation of nanocones with different apex angles shows the advantageous
      properties of cones with the smallest angles.

PMID- 30118229
TI  - Structural Tuning of Quantum Decoherence and Coherent Energy Transfer in
      Photosynthetic Light Harvesting.
AB  - Photosynthetic organisms capture energy from solar photons by constructing light
      harvesting proteins containing arrays of electronic chromophores. Collective
      excitations (excitons) arise when energy transfer between chromophores is
      coherent, or wavelike, in character. Here we demonstrate experimentally that
      coherent energy transfer to the lowest-energy excitons is principally controlled
      in a light-harvesting protein by the temporal persistence of quantum coherence
      rather than by the strength of vibronic coupling. In the peridinin-chlorophyll
      protein from marine dinoflagellates, broad-band two-dimensional electronic
      spectroscopy reveals that replacing the native chlorophyll a acceptor
      chromophores with chlorophyll b slows energy transfer from the carotenoid
      peridinin to chlorophyll despite narrowing the donor-acceptor energy gap. The
      formyl substituent on the chlorophyll b macrocycle hastens decoherence by sensing
      the surrounding electrostatic noise. These findings demonstrate how quantum
      coherence enhances the efficiency of energy transfer despite being very short
      lived in light-harvesting proteins at physiological temperatures.

PMID- 30118230
TI  - Optical Coherent Reflection from a Confined Colloidal Film: Modeling and
      Experiment.
AB  - We study the optical reflectivity of confined colloidal films as a function of
      the angle of incidence in an internal reflection configuration. Two effective
      medium models and an extended coherent-scattering model for thin colloidal films
      are compared against experimental measurements with gold, latex, and titanium
      dioxide colloids. A derivation of the coherent scattering model for confined
      colloidal films used in this work is presented in a comprehensive way. The model
      lies within the framework of the multiple-scattering theory and is valid for any
      angle of incidence and for colloids of small or large particles compared to the
      wavelength of light, however, only for small and moderately small particles'
      volume fraction. Reflectivity versus angle of incidence curves for an opaque
      colloidal film in an internal reflection configuration show the effects of two
      critical angles. Within the two critical angles, there is a high sensitivity to
      the presence of colloidal particles, while the volume of colloidal samples needed
      is in the microliter range. Upon comparing theory with experiment, no model
      fitting was done in any case. The experimental setup and its calibration
      procedure are discussed. The results provide physical insight into applications
      involving optical properties of colloidal systems.

PMID- 30118231
TI  - Heterogeneous Reaction of HCOOH on NaCl Particles at Different Relative
      Humidities.
AB  - The contribution of volatile organic acids to chloride depletion still remains
      unclear under ambient conditions in the coast and inland. In this work, the
      heterogeneous reaction of HCOOH on the NaCl surface at a series of relative
      humidities (RHs) was investigated using diffuse reflectance infrared Fourier
      transform spectroscopy (DRIFTS). The formate was found to be formed on NaCl
      surface under dry and wet conditions, accompanied by the corresponding chloride
      depletion. The adsorbed HCOOH and the formation of formate on NaCl surface
      decreased with increasing RH below 30% RH. The adsorbed HCOOH decreased, while
      the formation of formate increased with enhanced RH at 45-70% RH. The variation
      in the formation of formate with RH suggests that chloride depletion may undergo
      similar changes. Additionally, the mechanism and kinetics for uptake of HCOOH on
      NaCl surface at various RHs were discussed and analyzed. Our results highlight
      the role of heterogeneous chemistry of volatile organic acid in the chloride
      depletion of NaCl in the coast and inland.

PMID- 30118232
TI  - Heterogeneity in the Folding of Villin Headpiece Subdomain HP36.
AB  - Small single domain proteins that fold on the microsecond time scale have been
      the subject of intense interest as models for probing the complexity of folding
      energy landscapes. The villin headpiece subdomain (HP36) has been extensively
      studied because of its simple three helix structure, ultrafast folding lifetime
      of a few microseconds, and stable native fold. We have previously shown that
      folding as measured by a single 13C?18O isotopic label on residue A57 in helix 2
      occurs at a different rate than that measured by global probes of folding,
      indicating noncooperative complexity in the folding of HP36. In order to
      determine whether this complexity reflects intermediates or parallel pathways
      over a small activation barrier, 13C?18O labels were individually incorporated at
      six different positions in HP36, including into all 3 helices. The equilibrium
      thermal unfolding transitions and the folding/unfolding dynamics were monitored
      using the unique IR signature of the 13C?18O label by temperature dependent FTIR
      and temperature jump IR spectroscopy, respectively. Equilibrium experiments
      reveal that the 13C?18O labels at different positions in HP36 show drastic
      differences in the midpoint of their transitions ( Tm), ranging from 45 to 67 
      degrees C. Heterogeneity is also observed in the relaxation kinetics; there are
      differences in the microsecond phase when different labeled positions are probed.
      At a final temperature of 45  degrees C, the relaxation rate for 13C?18O A57 is
      2.4e + 05 s-1 whereas for 13C?18O L69 HP36 the relaxation rate is 5.1e + 05 s-1,
      two times faster. The observation of site-dependent midpoints for the equilibrium
      unfolding transitions and differences in the relaxation rates of the labeled
      positions enables us to probe the progressive accumulation of the folded
      structure, providing insight into the microscopic details of the folding
      mechanism.

PMID- 30118233
TI  - Effects of Oligomer Length, Solvents, and Temperature on the Self-Association of
      Aromatic Oligoamide Foldamers.
AB  - The effects of oligomer length, solvent, and temperature on the self-association
      of stably folded short aromatic oligoamide are probed. With large flat surfaces,
      these aromatic oligoamides undergo stacking interaction with strength that
      increases nonlinearly with oligomer lengths. Opposite to typical aromatic
      stacking, the stacking of these molecules is enhanced in solvents of low
      polarity, but it is greatly weakened in polar solvents, especially those with
      hydrogen bond donors, and it is very sensitive to changes in temperature.

PMID- 30118234
TI  - Synthesis of Cyclic beta-Silylalkenyl Triflates via an Alkenyl Cation
      Intermediate.
AB  - Trimethylsilylalkyne derivatives are transformed into cyclic beta-silylalkenyl
      triflates through cationic cyclization and subsequent trapping of the alkenyl
      cation by a triflate anion. beta-Silylcyclohexenyl triflates and 3-trimethylsilyl
      1,4-dihydronaphth-2-yl triflates are generated efficiently using this
      methodology. These products provide ready access to substituted cyclohexynes,
      exemplified by a concise total synthesis of beta-apopicropodophyllin.

PMID- 30118235
TI  - NIR-Absorbing Dye Based on BF2-Bridged Azafulvene Dimer as a Strong Electron
      Accepting Unit.
AB  - BF2-bridged azafulvene dimers designed to be strong electron-accepting units were
      selectively synthesized using a bulky base. Single-crystal X-ray diffraction
      analysis revealed that the high electron-accepting ability of this structure
      stems from the contribution of the pi-conjugation mode of the azafulvene dimer
      upon formation of B-N coordination bonds. As a result of the low-lying LUMO
      energy of this electron-accepting unit, the corresponding D-A-D dye exhibits an
      intense NIR absorption band at 922 nm, which tails up to 1150 nm, while
      significant absorption bands in the visible region are absent. As a NIR dye this
      molecule exhibits moreover exceptional photostability and resistance to oxidation
      by atmospheric oxygen, even in dilute solution.

PMID- 30118236
TI  - Preparation and Characterization of Polyimide Aerogels with a Uniform Nanoporous
      Framework.
AB  - Polyimide (PI) aerogels were successfully synthesized via a straightforward sol
      gel process under room temperature along with the supercritical CO2 drying method
      using 4-amino- N-methylbenzamide and 3,3',4,4'-biphenyltetracarboxylic
      dianhydride. 1,3,5-Triaminophenoxybenzene was used as the cross-linker. The
      chemical structure, pore structure, morphology, thermal performance, CO2
      adsorption, and mechanical performance of PI aerogels were investigated. The as
      prepared PI aerogels had low bulk densities (0.091-0.167 g/cm3), low shrinkages
      (9.73-17.36%), low thermal conductivities (0.0307-0.0341 W/m.K), high specific
      surface areas (449.76-538.19 m2/g), small pore diameter (10.37-22.41 nm), high
      thermal stability (onset of decomposition above 560  degrees C), and excellent
      mechanical property. The CO2 adsorption capacities of PI aerogels were
      substantially higher than the values of the previous porous materials reported
      under the similar conditions, and the CO2 uptake capacity was as high as 31.19
      cm3/g at 25  degrees C and 1.0 bar. The resulting PI aerogels could be
      potentially used as thermal insulators and CO2 adsorbents.

PMID- 30118237
TI  - B2pin2-Mediated Palladium-Catalyzed Diacetoxylation of Aryl Alkenes with O2 as
      Oxygen Source and Sole Oxidant.
AB  - A novel palladium-catalyzed alkene diacetoxylation with dioxygen (O2) as both the
      sole oxidant and oxygen source is developed, which was identified by 18O-isotope
      labeling studies. Control experiments suggested that bis(pinacolato)diboron
      (B2pin2) played a dominant intermediary role in the formation of a C-O bond. This
      method performed good functional group tolerance with moderate to excellent
      yields, which could be successfully applied to the late-stage modification of
      natural products. Furthermore, an atmospheric pressure of dioxygen enhances the
      practicability of the protocol.

PMID- 30118238
TI  - Asymmetric Synthesis of a Potent CXCR7 Modulator Featuring a Hindered Tertiary
      beta-Amino Amide Stereocenter.
AB  - A practical and asymmetric synthesis of a small-molecule CXCR7 modulator
      featuring a highly functionalized and hindered tertiary beta-amino amide
      framework is reported. The cornerstone of this strategy relied on the
      intermediacy of a reactive aziridinium species, which, following regioselective
      ring opening with cyanide, furnished the desired chiral beta-tertiary amino
      nitrile for further elaboration. As a means of further highlighting this
      synthetic strategy, an expanded scope of hindered beta-amino amide synthesis is
      also presented.

PMID- 30118239
TI  - Susceptibility of Antibody CDR Residues to Chemical Modifications Can Be Revealed
      Prior to Antibody Humanization and Aid in the Lead Selection Process.
AB  - A critical part of the clinical development path for a therapeutic antibody
      involves evaluating the physical and chemical stability of candidate molecules
      throughout the manufacturing process. In particular, the risks of chemical
      liabilities that can impact antigen binding, such as deamidation, oxidation, and
      isomerization in the antibody CDR sequences, need to be controlled through
      formulation development or eliminated by replacing the amino acid motif
      displaying the chemical instability. Commonly, the antibody CDR sequence contains
      multiple sequence motifs (potential hotspots) for chemical instability. However,
      only a subset of these motifs results in actual chemical modification, and thus,
      experimental assessment of the extent of instability is necessary to identify
      positions for potential sequence engineering. Ideally, this information should be
      available prior to antibody humanization at the stage of parental rodent antibody
      identification. Early knowledge of liabilities allows for ranking of clones or
      the mitigation of liabilities by concurrent engineering with the antibody
      humanization process instead of time-consuming sequential activities. However,
      concurrent engineering of chemical liabilities and humanization requires
      translatability of the chemical modifications from the rodent parental antibody
      to the humanized. We experimentally compared the stability of all sequence motifs
      by mass spectrometric peptide mapping between the rodent parental antibody and
      the final humanized antibody and observed a linear correlation. These results
      have enabled a streamlined developability assessment process for therapeutic
      antibodies from lead discovery to clinical development.

PMID- 30118240
TI  - Synthesis of Complex Stereoheptads en Route to Daphnane Diterpene Orthoesters.
AB  - Tricyclic cores of the daphnane diterpene orthoesters (DDOs) are synthesized in
      10 steps from readily available materials. Key to their assembly is the
      development of a stereocontrolled p-quinol functionalization sequence which
      enables rapid access to DDO C-ring stereopolyads from simple precursors. Problems
      encountered in stereo- and regioselectivity are highlighted and solved by exact
      changes in choreography, although it is shown that the undesired stereochemical
      outcomes also proceed with high selectivity.

PMID- 30118241
TI  - Effects of aerobic exercise and vitamin C supplementation on rhinitis symptoms in
      allergic rhinitis patients.
AB  - INTRODUCTION: Exercise training and vitamin C supplementation have both been
      recommended as an effective adjuvant treatment in the management of symptoms in
      patients with many diseases. However, its effects on rhinitis symptoms remain
      unclear. The aim of the present study was to determine the effects of exercise
      training alone, and in combination with vitamin C supplementation, on rhinitis
      symptoms in allergic rhinitis patients. METHODS: Twenty-seven rhinitis patients
      were randomized into 3 groups: control (CON; n = 8), exercise (EX; n = 9), and
      exercise combined with vitamin C (EX + Vit.C; n = 10). The exercise training
      protocol consisted of walking and/or running on a treadmill at 65-70% heart rate
      reserve for 30 min per session, 3 times per week for 8 weeks. The EX + Vit.C
      group ingested 2,000 mg vitamin C per day. RESULTS: After 8 weeks, both EX and EX
      + Vit.C groups increased peak aerobic capacity and peak nasal inspiratory flow
      (PNIF) and exhibited significantly decreased rhinitis symptoms, nasal blood flow
      (NBF) and malondialdehylde levels compared to pre-test. Rhinitis symptoms and NBF
      after nasal challenge with house dust mite decreased significantly in the EX and
      EX + Vit.C groups. The EX and EX + Vit.C groups had significantly lower nasal
      secretion interleukin (IL)-4, but higher nasal secretion IL-2 levels, than the
      CON group. CONCLUSIONS: This study clearly confirms that aerobic exercise
      training significantly improved clinical of allergic rhinitis and cytokine
      profiles. Nonetheless, with the limited power of small sample size, whether
      adding vitamin C is any beneficial is not shown. A larger randomized controlled
      trial is thus warranted.

PMID- 30118242
TI  - The cooperation of pharmacologic-dose ascorbate with ceftriaxone against
      Staphylococcus aureus through bactericidal synergy and enhanced macrophage
      killing activity.
AB  - BACKGROUND: Ascorbate is a low-cost compound with a known bactericidal-synergy to
      antibitics. However, the synergy depends on concentrations and organisms. Thus,
      the synergy test by time-kill assay might be appropriate for the screening of the
      synergy. OBJECTIVE: We aimed to test the adjuvant property of ascorbate with
      ceftriaxone, a frequently prescribed beta-lactam antibiotic. METHOD: Ascorbate
      was tested with several bacteria from the American Type Culture Collection (ATCC)
      including Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii
      and Escherichia coli for i) bactericidal property of ascorbate, alone or with
      ceftriaxone-combination, by time-kill assay, ii) an influence on the killing
      activity of bone -marrow-derived macrophage and iii) the attenuation of myositis
      mouse model. RESULT: The bactericidal synergy (determined with time-kill assay at
      24 h) against S. aureus, but not other selected bacteria, was demonstrated in
      ascorbate (10 and 40 mM) plus ceftriaxone at the minimal inhibitory concentration
      (1x MIC). Ascorbate alone, without antibiotic, enhanced macrophage killing
      activity and directly eliminated bacteria at the concentration 10-40mM and 250mM,
      respectively (both properties presented against S. aureus and P. aeruginosa, but
      not other bacteria). Ascorbate with ceftriaxone also reduced bacterial burdens in
      muscle and serum cytokines of S. aureus -myositis mouse model. Moreover, the
      synergy against the clinical isolated methicillin resistant S. aureus (MRSA) by
      time-kill assay and myositis model also presented. CONCLUSION: Ascorbate
      ceftriaxone synergy against S. aureus was demonstrated by time-kill assay and
      myositis model. Time-kill assy might be valuable as a screening test to select
      the patients that potentially benefit from ascorbate- ceftriaxone adjuvant
      therapy.

PMID- 30118243
TI  - Comparison between pediatric respiratory assessment measure (PRAM) score and wood
      asthma score to assess acute asthma exacerbation.
AB  - BACKGROUND: Wood's score, the assessment of childhood respiratory failure, has
      been used to assess childhood acute asthma severity in Thailand since 19th
      century. However, PRAM score, which is increasingly used in Western countries has
      not been evaluated among Thai children with asthma. OBJECTIVES: This study aims
      to determine whether Wood or PRAM score is better prediction of severity of
      childhood asthma exacerbation. METHODS: The prospective comparative study of
      severity asthma score was performed in asthmatic children, 2-18 years old, with
      acute asthma exacerbation at Queen Sirikit National Institute of Child Health.
      PRAM and Wood's score were separately determined by 2 physicians. The patients
      were further assessed at 0, 4 or 24 hours after their admissions. The asthma
      treatment followed GINA guideline. RESULTS: There were 80 asthmatic patients,
      mean aged 5.71 +/- 2.95 years. The admission rate was 28.8% with the mean length
      of stay = 4 +/- 1 days. PRAM was correlated with Wood's score (Spearman's
      correlation p = 0.900, p < 0.001 at triage, and = p0.981, p < 0.001). The
      highlight of this study is the finding that intraclass correlation of PRAM is
      better than Wood asthma score (ICC = 0.944; 95%CI 0.913-0.964, 0.898; 95%CI 0.841
      0.935, respectively). ROC indicated Wood's score <= 4 and PRAM <= 5, in the
      requirement for admission. CONCLUSION: PRAM and Wood's score are both promising
      in prediction of severity and outcome of childhood asthma exacerbation.

PMID- 30118244
TI  - A hereditary angioedema screening on an index case: Turkey.
AB  - BACKGROUND: Hereditary angioedema (HAE) is characterised by recurrent episodes of
      angioedema and can be fatal. OBJECTIVE: The present study aimed to screen HAE.
      METHODS: A total of 60 individuals were screened. The frequency and severity of
      symptoms were scored from 0 to 8. Measurements were taken of C4 and C1 esterase
      inhibitor protein (C1-INH) levels. Mutation in the C1 inhibitor gene was examined
      in 9 patients with HAE. RESULTS: A positive correlation between the C1esterase
      inhibitor proteinlevels and C4 level was detected in the group as a whole (p <
      0.001, r = 0.725, n = 60). Anegative correlation between the C1 esterase
      inhibitor protein level and severity score was observed in the whole group (p <
      0.001, r = -0.486, n = 60). A negative correlation was also detected in the
      entire group between the C4 level and severity score (p = 0.002, r = -0.389, n =
      60). In the patients with HAE, a positive correlation between the C1 esterase
      inhibitor protein level and C4 levels was detected (p = 0.034, r = 0.705, n = 9).
      A heterozygous c. 601A > T nonsense variant was identified at the C1 esterase
      inhibitor gene-SERPING1-in patients with Type 1 HAE. CONCLUSION: It is well known
      that there is a prolonged delay in the diagnosis of HAE. The present study
      demonstrates that it is very important and even life-saving to screen for HAE on
      the basis of an index case.

PMID- 30118245
TI  - Clinical characteristics of exogenous progestogen hypersensitivity.
AB  - BACKGROUND: Autoimmune progesterone dermatitis is a rare disease characterized by
      eruption recurrence in the luteal phase of each menstrual cycle. As synthetic
      progesterones are increasingly used for assisted reproductive techniques (ARTs)
      for infertility or prevention of abortion, cases of dermatitis caused by
      exogenous progesterone have been reported. OBJECTIVE: To investigate the clinical
      characteristics of exogenous progestogen hypersensitivity (PH). METHODS: We
      retrospectively reviewed data from patients presenting with dermatitis induced by
      exogenous progesterone between 2011 and 2016. RESULTS: Nine patients had
      exogenous PH. Six patients were treated with progesterone for threatened
      abortion, and three for ARTs. Their mean age was 33.6 years, and their mean body
      mass index was 26.3 kg/m2. They had never experienced an adverse drug reaction.
      The mean latency to symptom onset was 5.8 days (range 1 h to 11 days). The
      patients complained of hives, erythema and itching, and one developed
      anaphylaxis. All patients were treated with antihistamines, and six patients were
      treated with systemic corticosteroids. Epinephrine was administered to one
      patient with hypotension. The symptom duration was 1-14 days. Skin tests were
      performed in four patients; all were positive. Two patients were treated
      successfully by progesterone desensitization. CONCLUSIONS: The clinical features
      of exogenous PH were similar to those of type I hypersensitivity reactions, but
      tended to develop later and did not respond to antihistamines or steroids. As use
      of progesterone increases, an understanding of the clinical features of exogenous
      PH becomes ever-more important.

PMID- 30118246
TI  - Role of Toll-like receptor 2 in mediating the production of cytokines and human
      beta-defensins in oral mucosal epithelial cell response to Leptospiral infection.
AB  - BACKGROUND: Pathogenic Leptospira spp. is the causative agent of leptospirosis.
      Oral mucosal cavity is one of portal entry for this bacterium. Oral mucosal
      epithelium provides a physical barrier and secretes cytokines, chemokines and
      antimicrobial peptides (AMPs) in response to microbial infection. Human beta
      defensins (hBDs); hBD1, hBD2, and hBD3 are predominantly AMPs expressed in the
      oral cavity. Toll-like receptors (TLRs) have been reported in hBD regulation.
      TLR2 recognizes leptospiral lipopolysaccharide, and plays a key role in the early
      control of leptospirosis. OBJECTIVE: The aim of this study is to investigate the
      role of TLR2 in mediating the production of cytokines and hBDs in oral mucosal
      epithelial cell response to leptospiral infection. METHODS: Cultivated oral
      mucosal epithelial cells were prepared, characterized, and compared with oral
      mucosal tissues. The TLR1-10 and hBD mRNA expressions were examined. Pro
      inflammatory cytokine and hBD1-3 expressions in response to leptospires were
      determined by quantitative (q) RT-PCR. RESULTS: The cultivated oral epithelium
      expressed TLR2 and hBD1-3. The induction of IL-betaIL-8, TNF-alpha, and hBD2 were
      increased in response to Leptospira via TLR2 recognition. CONCLUSION: The
      characteristics of primary epithelial cells and tissue were similar in terms of
      TLR expression. All primary epithelial cells expressed TLR2 and hBD1-3. We used
      primary epithelial cells to study response to L. interrogans. Our results yielded
      the first evidence that human TLR2 regulates hBD2 expression in oral mucosa
      epithelial responded to L. interrogans. Expression of hBD2 may act to neutralize
      the virulence or prevent the invasion of L. interrogans at the portal of entry.

PMID- 30118247
TI  - Involvement of Toll-like receptor 2 on human corneal epithelium during an
      infection of Pythium insidiosum.
AB  - BACKGROUND: Pythium insidiosum, a pathogenic oomycete, is a common causative
      organism of infectious corneal ulcer. Studying the innate immune response at the
      ocular surface is important for better understanding of the underlying
      pathogenesis and host defense against P. insidiosum infection. OBJECTIVE: The
      present study aims to investigate the role of Toll-like receptor (TLR)2 on human
      corneal epithelial cells (HCECs) in P. insidiosum infection. METHODS: Human
      embryonic kidney (HEK) cells were stimulated with either P. insidiosum zoospores
      or hyphae. NF-kappaB activation was determined by spectrophotometric measurement
      of secreted embryonic alkaline phosphatase (SEAP) levels. The role of TLR2 in P.
      insidiosum infection was studied in HCECs and monocyte derived macrophages (MDMs)
      using anti-TLR2 neutralizing antibody. The expression levels of pro-inflammatory
      cytokines were determined. RESULTS: Both P. insidiosum hypha and zoospore
      stimulated TLR2-dependent NF-kappaB activation in HEK-BlueTM-hTLR2 cells in dose
      dependent manner. IL-6 and IL-8, but not IL-1beta, were upregulated in HCECs
      after stimulation with P. insidiosum. Blockade of TLR2 on HCECs altered neither
      IL-6 nor IL-8 expressions. In contrast, the 3 cytokines were upregulated in the
      stimulated MDMs and the expression levels of IL-1beta and IL-8 but not IL-6 were
      attenuated in TLR2 blockade MDMs. CONCLUSION: P. insidiosum was recognized by
      human TLR2 on HEK cells. The mRNA expression levels of certain cytokines were
      dependent of TLR2 in P. insidiosum infected MDMs but not HCECs at early stage of
      infection.

PMID- 30118248
TI  - Down-regulation of let-7a and miR-21 in urine exosomes from lupus nephritis
      patients during disease flare.
AB  - BACKGROUND: The contents of exosomes determine their biological functions and
      represent a new class of epigenetic modulation of renal cells considering as
      novel class of biomarker. OBJECTIVE: Our study aims to investigate the expression
      of microRNAs (miRNA), including miR-10a/b, let-7a, and miR-21, in urinary
      exosomes isolated from patients with active lupus nephritis (LN) compared to
      inactive LN. METHODS: The exosomes were obtained from long-term follow up LN
      patients during active and 4 months after treatment (n = 3). The expression of
      candidate miRNAs was validated in group of LN patients with renal flare (n = 13)
      and remission stage (n = 18) using qPCR. All exosomes were characterized by
      NanoSight and western blotting. The correlation between miRNA expressions and
      kidney functions was studied. RESULTS: We found that let-7a and miR-21, but not
      miR-10a/b, were significantly down-regulated in LN patients with active disease
      compared with inactive disease. Long-term follow-up patients also showed down
      regulation of let-7a and miR-21 during disease flare while the expressions were
      elevated after complete course of treatment. Although the miRNA expressions were
      not significantly correlated with classical kidney injury markers, negative
      correlations were found in both protein leakages and glomerular filtration rate.
      CONCLUSION: Our result suggested that urinary exosome-associated miRNA, let-7a
      and miR-21, could be used to guide the clinical stage of LN patients and possibly
      plays a role in epigenetic regulation of the kidney during the disease. Its
      expression might be able to use as liquid biopsy, however, validation in large
      sample size is required to show it significant in clinical implication.

PMID- 30118249
TI  - Statistics and Dynamics of the Center-of-Mass Coordinate in a Quantum Liquid.
AB  - Motivated by recent experiments in ultracold gases, we focus on the properties of
      the center-of-mass coordinate of an interacting one-dimensional Fermi gas,
      displaying several distinct phases. While the variance of the center of mass
      vanishes in insulating phases such as phase-separated and charge density wave
      phases, it remains finite in the metallic phase, which realizes a Luttinger
      liquid. By combining numerics with bosonization, we demonstrate that the
      autocorrelation function of the center-of-mass coordinate is universal throughout
      the metallic phase. It exhibits persistent oscillations, and its short time
      dynamics reveal important features of the quantum liquid, such as the Luttinger
      liquid parameter and the renormalized velocity. The full counting statistics of
      the center of mass follows a normal distribution already for small systems. Our
      results apply to nonintegrable systems as well and are within experimental reach
      for, e.g., carbon nanotubes and cold atomic gases.

PMID- 30118250
TI  - Observation of Efficient Lower Hybrid Current Drive at High Density in Diverted
      Plasmas on the Alcator C-Mod Tokamak.
AB  - Efficient lower hybrid current drive (LHCD) is demonstrated at densities up to
      n[over -]_{e}~1.5*10^{20}  m^{-3} in diverted plasmas on the Alcator C-Mod
      tokamak by operating at increased plasma current-and therefore reduced Greenwald
      density fraction. This density exceeds the nominal "LH density limit" at n[over 
      ]_{e}~1.0*10^{20}  m^{-3} reported previously, above which an anomalous loss of
      current drive efficiency was observed. The recovery of current drive efficiency
      to a level consistent with engineering scalings is correlated with a reduction in
      density shoulders and turbulence levels in the far scrape-off layer.
      Concurrently, rf wave interaction with the edge and/or scrape-off-layer plasma is
      reduced, as indicated by a minimal broadening of the wave frequency spectrum
      measured at the plasma edge. These results have important implications for
      sustaining steady-state tokamak operation and indicate a pathway forward for
      implementing efficient LHCD in a reactor.

PMID- 30118252
TI  - Growing Critical: Self-Organized Criticality in a Developing Neural System.
AB  - Experiments in various neural systems found avalanches: bursts of activity with
      characteristics typical for critical dynamics. A possible explanation for their
      occurrence is an underlying network that self-organizes into a critical state. We
      propose a simple spiking model for developing neural networks, showing how these
      may "grow into" criticality. Avalanches generated by our model correspond to
      clusters of widely applied Hawkes processes. We analytically derive the cluster
      size and duration distributions and find that they agree with those of
      experimentally observed neuronal avalanches.

PMID- 30118253
TI  - Suppression of Heating in Quantum Spin Clusters under Periodic Driving as a
      Dynamic Localization Effect.
AB  - We investigate numerically and analytically the heating process in ergodic
      clusters of interacting spins 1/2 subjected to periodic pulses of an external
      magnetic field. Our findings indicate that there is a threshold for the pulse
      strength below which the heating is suppressed. This threshold decreases with the
      increase of the cluster size, approaching zero in the thermodynamic limit, yet it
      should be observable in clusters with fairly large Hilbert spaces. We obtain the
      above threshold quantitatively as a condition for the breakdown of the golden
      rule in the second-order perturbation theory. It is caused by the phenomenon of
      dynamic localization.

PMID- 30118251
TI  - First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector.
AB  - We present the first limits on inelastic electron-scattering dark matter and dark
      photon absorption using a prototype SuperCDMS detector having a charge resolution
      of 0.1 electron-hole pairs (CDMS HVeV, a 0.93 g CDMS high-voltage device). These
      electron-recoil limits significantly improve experimental constraints on dark
      matter particles with masses as low as 1  MeV/c^{2}. We demonstrate a sensitivity
      to dark photons competitive with other leading approaches but using substantially
      less exposure (0.49 g d). These results demonstrate the scientific potential of
      phonon-mediated semiconductor detectors that are sensitive to single electronic
      excitations.

PMID- 30118254
TI  - Width Scaling of an Interface Constrained by a Membrane.
AB  - We investigate the shape of a growing interface in the presence of an
      impenetrable moving membrane. The two distinct geometrical arrangements of the
      interface and membrane, obtained by placing the membrane behind or ahead of the
      interface, are not symmetrically related. On the basis of numerical results and
      an exact calculation, we argue that these two arrangements represent two distinct
      universality classes for interfacial growth: while the well-established Kardar
      Parisi-Zhang (KPZ) growth is obtained in the "ahead" arrangement, we find an
      arrested KPZ growth with a smaller roughness exponent in the "behind"
      arrangement. This suggests that the surface properties of growing cell membranes
      and expanding bacterial colonies, for example, are fundamentally distinct.

PMID- 30118255
TI  - Emergent Magnetic Degeneracy in Iron Pnictides due to the Interplay between Spin
      Orbit Coupling and Quantum Fluctuations.
AB  - Recent experiments in iron pnictide superconductors reveal that, as the putative
      magnetic quantum critical point is approached, different types of magnetic order
      coexist over a narrow region of the phase diagram. Although these magnetic
      configurations share the same wave vectors, they break distinct symmetries of the
      lattice. Importantly, the highest superconducting transition temperature takes
      place close to this proliferation of near-degenerate magnetic states. In this
      Letter, we employ a renormalization group calculation to show that such a
      behavior naturally arises due to the effects of spin-orbit coupling on the
      quantum magnetic fluctuations. Formally, the enhanced magnetic degeneracy near
      the quantum critical point is manifested as a stable Gaussian fixed point with a
      large basin of attraction. Implications of our findings to the superconductivity
      of the iron pnictides are also discussed.

PMID- 30118256
TI  - Landau Level Diagram and the Continuous Rotational Symmetry Breaking in Trilayer
      Graphene.
AB  - The sequence of the zeroth Landau levels (LLs) between filling factors nu=-6 to 6
      in ABA-stacked trilayer graphene (TLG) is unknown because it depends sensitively
      on the nonuniform charge distribution on the three layers of ABA-stacked TLG.
      Using the sensitivity of quantum Hall data on the electric field and magnetic
      field, in an ultraclean ABA-stacked TLG sample, we quantitatively estimate the
      nonuniformity of the electric field and determine the sequence of the zeroth LLs.
      We also observe anticrossings between some LLs differing by 3 in LL index, which
      result from the breaking of the continuous rotational to C_{3} symmetry by the
      trigonal warping.

PMID- 30118257
TI  - Second-Order Hydrodynamics in Next-to-Leading-Order QCD.
AB  - We compute the hydrodynamic relaxation times tau_{pi} and tau_{j} for hot QCD at
      next-to-leading order in the coupling with kinetic theory. We show that certain
      dimensionless ratios of second-order to first-order transport coefficients obey
      bounds which apply whenever a kinetic theory description is possible; the
      computed values lie somewhat above these bounds. Strongly coupled theories with
      holographic duals strongly violate these bounds, highlighting their distance from
      a quasiparticle description.

PMID- 30118258
TI  - Erratum: Primordial Black Hole Scenario for the Gravitational-Wave Event GW150914
      [Phys. Rev. Lett. 117, 061101 (2016)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.117.061101.

PMID- 30118259
TI  - Design for a Nanoscale Single-Photon Spin Splitter for Modes with Orbital Angular
      Momentum.
AB  - We propose using the effective spin-orbit coupling of light in Bragg-modulated
      cylindrical waveguides for the efficient separation of spin-up and spin-down
      photons emitted by a single photon emitter. Because of the spin and directional
      dependence of photonic stop bands in the waveguides, spin-up (-down) photon
      propagation in the negative (positive) direction along the waveguide axis is
      blocked while the same photon freely propagates in the opposite direction.
      Frequency shifts of photonic band structures induced by the spin-orbit coupling
      are verified by finite-difference time-domain numerical simulations.

PMID- 30118261
TI  - Plastic Deformation in a Quantum Solid: Dislocation Avalanches and Creep in
      Helium.
AB  - Conventional solids deform elastically for small stresses-reversibly with a
      linear, rate-independent relationship between stress and strain. Beyond the yield
      point, plastic deformation begins-irreversible, nonlinear, and time dependent.
      Plasticity involves the motion and multiplication of dislocations, and here we
      report observations of such "metallurgical" phenomena in hcp ^{4}He, a solid
      whose defect behavior is dominated by quantum effects. Below 0.4 K, there is a
      strain threshold for elastic deformation above which sudden stress drops and
      acoustic emissions appear, the signatures of dislocation avalanches. The
      dimensions of these slip events range from millimeters to microns. At higher
      temperatures, the avalanches are replaced by continuous creep involving
      dislocations, and we observe steady flow at stresses as low as 400 Pa.

PMID- 30118262
TI  - Crackling Dynamics in the Mechanical Response of Knitted Fabrics.
AB  - Crackling noise, which occurs in a wide range of situations, is characterized by
      discrete events of various sizes, often correlated in the form of avalanches. We
      report experimental evidence that the mechanical response of a knitted fabric
      displays such broadly distributed events both in the force signal and in the
      deformation field, with statistics analogous to that of earthquakes or soft
      amorphous materials. A knit consists of a regular network of frictional contacts,
      linked by the elasticity of the yarn. When deformed, the fabric displays
      spatially extended avalanchelike yielding events resulting from collective
      interyarn contact slips. We measure the size distribution of these avalanches, at
      the stitch level from the analysis of nonelastic displacement fields and
      externally from force fluctuations. The two measurements yield consistent power
      law distributions reminiscent of those found in other avalanching systems. Our
      study shows that a knitted fabric is not only a thread-based metamaterial with
      highly sought after mechanical properties, but also an original, model system,
      with topologically protected structural order, where an intermittent, scale
      invariant response emerges from minimal ingredients, and thus a significant
      landmark in the study of out-of-equilibrium universality.

PMID- 30118263
TI  - Critical Dynamics of Natural Time-Varying Images.
AB  - A deep understanding of the dynamical properties of natural time-varying images
      is essential for interpreting how they are efficiently processed in the brain.
      Here we examine natural time-varying images from the perspective of their
      spatiotemporal patterns and find evidence of dynamical thermodynamic criticality.
      We further demonstrate that these spatiotemporal patterns ubiquitously organize
      as localized, propagating patterns. By studying these propagating patterns and
      their spreading dynamics over time, we demonstrate that the critical dynamics of
      natural time-varying images belong to the universality class of directed
      percolation. These critical dynamics have important implications for
      understanding neural processing of time-varying stimuli.

PMID- 30118260
TI  - Observation of an Excited Omega^{-} Baryon.
AB  - Using data recorded with the Belle detector, we observe a new excited hyperon, an
      Omega^{*-} candidate decaying into Xi^{0}K^{-} and Xi^{-}K_{S}^{0} with a mass of
      2012.4+/-0.7(stat)+/-0.6(syst)  MeV/c^{2} and a width of Gamma=6.4_{
      2.0}^{+2.5}(stat)+/-1.6(syst)  MeV. The Omega^{*-} is seen primarily in
      Upsilon(1S),Upsilon(2S), and Upsilon(3S) decays.

PMID- 30118265
TI  - Pseudoelasticity at Large Strains in Au Nanocrystals.
AB  - Pseudoelasticity in metals is typically associated with phase transformations
      (e.g., shape memory alloys) but has recently been observed in sub-10 nm Ag
      nanocrystals that rapidly recovered their original shape after deformation to
      large strains. The discovery of pseudoelasticity in nanoscale metals dramatically
      changes the current understanding of the properties of solids at the smallest
      length scales, and the motion of atoms at surfaces. Yet, it remains unclear
      whether pseudoelasticity exists in different metals and nanocrystal sizes. The
      challenge of observing deformation at atomistic to nanometer length scales has
      prevented a clear mechanistic understanding of nanoscale pseudoelasticity,
      although surface diffusion and dislocation-mediated processes have been proposed.
      We further the understanding of pseudoelasticity in nanoscale metals by using a
      diamond anvil cell to compress colloidal Au nanocrystals under quasihydrostatic
      and nonhydrostatic pressure conditions. Nanocrystal structural changes are
      measured using optical spectroscopy and transmission electron microscopy and
      modeled using electrodynamic theory. We find that 3.9 nm Au nanocrystals exhibit
      pseudoelastic shape recovery after deformation to large uniaxial strains of up to
      20%, which is equivalent to an ellipsoid with an aspect ratio of 2. Nanocrystal
      absorbance efficiency does not recover after deformation, which indicates that
      crystalline defects may be trapped in the nanocrystals after deformation.

PMID- 30118266
TI  - Inferring Network Connectivity from Event Timing Patterns.
AB  - Reconstructing network connectivity from the collective dynamics of a system
      typically requires access to its complete continuous-time evolution, although
      these are often experimentally inaccessible. Here we propose a theory for
      revealing physical connectivity of networked systems only from the event time
      series their intrinsic collective dynamics generate. Representing the patterns of
      event timings in an event space spanned by interevent and cross-event intervals,
      we reveal which other units directly influence the interevent times of any given
      unit. For illustration, we linearize an event-space mapping constructed from the
      spiking patterns in model neural circuits to reveal the presence or absence of
      synapses between any pair of neurons, as well as whether the coupling acts in an
      inhibiting or activating (excitatory) manner. The proposed model-independent
      reconstruction theory is scalable to larger networks and may thus play an
      important role in the reconstruction of networks from biology to social science
      and engineering.

PMID- 30118267
TI  - Nature of the Positron State in CdSe Quantum Dots.
AB  - Previous studies have shown that positron-annihilation spectroscopy is a highly
      sensitive probe of the electronic structure and surface composition of ligand
      capped semiconductor quantum dots (QDs) embedded in thin films. The nature of the
      associated positron state, however, whether the positron is confined inside the
      QDs or localized at their surfaces, has so far remained unresolved. Our positron
      annihilation lifetime spectroscopy studies of CdSe QDs reveal the presence of a
      strong lifetime component in the narrow range of 358-371 ps, indicating abundant
      trapping and annihilation of positrons at the surfaces of the QDs. Furthermore,
      our ab initio calculations of the positron wave function and lifetime employing a
      recent formulation of the weighted density approximation demonstrate the presence
      of a positron surface state and predict positron lifetimes close to experimental
      values. Our study thus resolves the long-standing question regarding the nature
      of the positron state in semiconductor QDs and opens the way to extract
      quantitative information on surface composition and ligand-surface interactions
      of colloidal semiconductor QDs through highly sensitive positron-annihilation
      techniques.

PMID- 30118268
TI  - Random Search with Resetting: A Unified Renewal Approach.
AB  - We provide a unified renewal approach to the problem of random search for several
      targets under resetting. This framework does not rely on specific properties of
      the search process and resetting procedure, allows for simpler derivation of
      known results, and leads to new ones. Concentrating on minimizing the mean
      hitting time, we show that resetting at a constant pace is the best possible
      option if resetting helps at all, and derive the equation for the optimal
      resetting pace. No resetting may be a better strategy if without resetting the
      probability of not finding a target decays with time to zero exponentially or
      faster. We also calculate splitting probabilities between the targets, and define
      the limits in which these can be manipulated by changing the resetting procedure.
      We moreover show that the number of moments of the hitting time distribution
      under resetting is not less than the sum of the numbers of moments of the
      resetting time distribution and the hitting time distribution without resetting.

PMID- 30118269
TI  - Maximum Elliptical Dichroism in Atomic Two-Photon Ionization.
AB  - Elliptical dichroism is known in atomic photoionization as the difference in the
      photoelectron angular distributions produced in nonlinear ionization of atoms by
      left- and right-handed elliptically polarized light. We theoretically demonstrate
      that the maximum dichroism |Delta_{ED}|=1 always appears in two-photon ionization
      of any atom if the photon energy is tuned in so that the electron emission is
      dominantly determined by two intermediate resonances. We propose the two-photon
      ionization of atomic helium in order to demonstrate this remarkable phenomenon.
      The maximum elliptical dichroism could be used as a sensitive tool for analyzing
      the polarization state of photon beams produced by free-electron lasers.

PMID- 30118270
TI  - Quantum Spin Liquid with Even Ising Gauge Field Structure on Kagome Lattice.
AB  - Employing large-scale quantum Monte Carlo simulations, we study the extended XXZ
      model on the kagome lattice. A Z_{2} quantum spin liquid phase with effective
      even Ising gauge field structure emerges from the delicate balance among three
      symmetry-breaking phases including stripe solid, staggered solid, and
      ferromagnet. This Z_{2} spin liquid is stabilized by an extended interaction
      related to the Rokhsar-Kivelson potential in the quantum dimer model limit. The
      phase transitions from the staggered solid to a spin liquid or ferromagnet are
      found to be first order and so is the transition between the stripe solid and
      ferromagnet. However, the transition between a spin liquid and ferromagnet is
      found to be continuous and belongs to the 3D XY^{*} universality class associated
      with the condensation of spinons. The transition between a spin liquid and stripe
      solid appears to be continuous and associated with the condensation of visons.

PMID- 30118264
TI  - Observation of Fine Time Structures in the Cosmic Proton and Helium Fluxes with
      the Alpha Magnetic Spectrometer on the International Space Station.
AB  - We present the precision measurement from May 2011 to May 2017 (79 Bartels
      rotations) of the proton fluxes at rigidities from 1 to 60 GV and the helium
      fluxes from 1.9 to 60 GV based on a total of 1*10^{9} events collected with the
      Alpha Magnetic Spectrometer aboard the International Space Station. This
      measurement is in solar cycle 24, which has the solar maximum in April 2014. We
      observed that, below 40 GV, the proton flux and the helium flux show nearly
      identical fine structures in both time and relative amplitude. The amplitudes of
      the flux structures decrease with increasing rigidity and vanish above 40 GV. The
      amplitudes of the structures are reduced during the time period, which started
      one year after solar maximum, when the proton and helium fluxes steadily
      increase. Above ~3  GV the p/He flux ratio is time independent. We observed that
      below ~3  GV the ratio has a long-term decrease coinciding with the period during
      which the fluxes start to rise.

PMID- 30118271
TI  - Invisible Anchors Trap Particles in Branching Junctions.
AB  - We combine numerical simulations and an analytic approach to show that the
      capture of finite, inertial particles during flow in branching junctions is due
      to invisible, anchor-shaped three-dimensional flow structures. These Reynolds
      number-dependent anchors define trapping regions that confine particles to the
      junction. For a wide range of Stokes numbers, these structures occupy a large
      part of the flow domain. For flow in a V-shaped junction, at a critical Stokes
      number, we observe a topological transition due to the merger of two anchors into
      one. From a stability analysis, we identify the parameter region of particle
      sizes and densities where capture due to anchors occurs.

PMID- 30118272
TI  - Large Flexoelectriclike Response from the Spontaneously Polarized Surfaces in
      Ferroelectric Ceramics.
AB  - Nonpoled ferroelectric ceramics are thought to be nonpolar because of randomly
      oriented grains and the formation of ferroelectric domains in the grains. Here,
      we discover the surfaces (~several  MUm thick) of ferroelectric ceramics are
      spontaneously polarized. Because the orientations of ferroelectric polarization
      of the opposite surfaces are antiparallel, ferroelectric ceramics are nonpolar as
      a whole. However, the ceramics exhibit a strong flexoelectriclike
      electromechanical response from the piezoelectric response of the polarized
      surfaces if they are asymmetrically strained (such as bending). Our results
      reveal a major mechanism to resolve one important but largely unresolved issue:
      the experimentally measured flexoelectric effect is typically orders of magnitude
      larger than the theoretically predicted value in ferroelectrics.

PMID- 30118273
TI  - Ultrafast Relaxation Dynamics of the Antiferrodistortive Phase in Ca Doped
      SrTiO_{3}.
AB  - The ultrafast dynamics of the octahedral rotation in Ca:SrTiO_{3} is studied by
      time-resolved x-ray diffraction after photoexcitation over the band gap. By
      monitoring the diffraction intensity of a superlattice reflection that is
      directly related to the structural order parameter of the soft-mode driven
      antiferrodistortive phase in Ca:SrTiO_{3}, we observe an ultrafast relaxation on
      a 0.2 ps timescale of the rotation of the oxygen octahedron, which is found to be
      independent of the initial temperature despite large changes in the corresponding
      soft-mode frequency. A further, much smaller reduction on a slower picosecond
      timescale is attributed to thermal effects. Time-dependent density-functional
      theory calculations show that the fast response can be ascribed to an ultrafast
      displacive modification of the soft-mode potential towards the normal state
      induced by holes created in the oxygen 2p states.

PMID- 30118274
TI  - Optical Control of the Topology of Laser-Plasma Accelerators.
AB  - We propose a twisted plasma accelerator capable of generating relativistic
      electron vortex beams with helical current profiles. The angular momentum of
      these vortex bunches is quantized, dominates their transverse motion, and results
      in spiraling particle trajectories around the twisted wakefield. We focus on a
      laser wakefield acceleration scenario, driven by a laser beam with a helical
      spatiotemporal intensity profile, also known as a light spring. We find that
      these light springs can rotate as they excite the twisted plasma wakefield,
      providing a new mechanism to control the twisted wakefield phase velocity and
      enhance energy gain and trapping efficiency beyond planar wakefields.

PMID- 30118275
TI  - Microsecond Valley Lifetime of Defect-Bound Excitons in Monolayer WSe_{2}.
AB  - In atomically thin two-dimensional semiconductors such as transition metal
      dichalcogenides (TMDs), controlling the density and type of defects promises to
      be an effective approach for engineering light-matter interactions. We
      demonstrate that electron-beam irradiation is a simple tool for selectively
      introducing defect-bound exciton states associated with chalcogen vacancies in
      TMDs. Our first-principles calculations and time-resolved spectroscopy
      measurements of monolayer WSe_{2} reveal that these defect-bound excitons exhibit
      exceptional optical properties including a recombination lifetime approaching 200
      ns and a valley lifetime longer than 1  MUs. The ability to engineer the crystal
      lattice through electron irradiation provides a new approach for tailoring the
      optical response of TMDs for photonics, quantum optics, and valleytronics
      applications.

PMID- 30118276
TI  - Dispersion of Air Bubbles in Isotropic Turbulence.
AB  - Bubbles play an important role in the transport of chemicals and nutrients in
      many natural and industrial flows. Their dispersion is crucial to understanding
      the mixing processes in these flows. Here we report on the dispersion of
      millimetric air bubbles in a homogeneous and isotropic turbulent flow with a
      Taylor Reynolds number from 110 to 310. We find that the mean squared
      displacement (MSD) of the bubbles far exceeds that of fluid tracers in
      turbulence. The MSD shows two regimes. At short times, it grows ballistically
      (?tau^{2}), while at larger times, it approaches the diffusive regime where the
      MSD?tau. Strikingly, for the bubbles, the ballistic-to-diffusive transition
      occurs one decade earlier than for the fluid. We reveal that both the enhanced
      dispersion and the early transition to the diffusive regime can be traced back to
      the unsteady wake-induced motion of the bubbles. Further, the diffusion
      transition for bubbles is not set by the integral timescale of the turbulence (as
      it is for fluid tracers and microbubbles), but instead, by a timescale of eddy
      crossing of the rising bubbles. The present findings provide a Lagrangian
      perspective towards understanding mixing in turbulent bubbly flows.

PMID- 30118277
TI  - Direct Observation of Atom-Ion Nonequilibrium Sympathetic Cooling.
AB  - Sympathetic cooling is the process of energy exchange between a system and a
      colder bath. We investigate this fundamental process in an atom-ion experiment
      where the system is composed of a single ion trapped in a radio-frequency Paul
      trap and prepared in a classical oscillatory motion with total energy of ~200  K,
      and the bath is an ultracold cloud of atoms at MUK temperature. We directly
      observe the sympathetic cooling dynamics with single-shot energy measurements
      during one to several collisions in two distinct regimes. In one, collisions
      predominantly cool the system with very efficient momentum transfer leading to
      cooling in only a few collisions. In the other, collisions can both cool and heat
      the system due to nonequilibrium dynamics in the presence of the ion trap's
      oscillating electric fields. While the bulk of our observations agree well with a
      molecular-dynamics simulation of hard-sphere (Langevin) collisions, a measurement
      of the scattering angle distribution reveals forward-scattering (glancing)
      collisions which are beyond the Langevin model. This work paves the way for
      further nonequilibrium and collision dynamics studies using the well-controlled
      atom-ion system.

PMID- 30118278
TI  - Connections between Mutually Unbiased Bases and Quantum Random Access Codes.
AB  - We present a new quantum communication complexity protocol, the promise-quantum
      random access code, which allows us to introduce a new measure of unbiasedness
      for bases of Hilbert spaces. The proposed measure possesses a clear operational
      meaning and can be used to investigate whether a specific number of mutually
      unbiased bases exist in a given dimension by employing semidefinite programming
      techniques.

PMID- 30118279
TI  - Dual Nature of Magnetism in a Uranium Heavy-Fermion System.
AB  - The duality between the localized and itinerant nature of magnetism in 5f
      electron systems has been a long-standing puzzle. Here, we report inelastic
      neutron scattering measurements, which reveal both local and itinerant aspects of
      magnetism in a single-crystalline system of UPt_{2}Si_{2}. In the
      antiferromagnetic state, we observe a broad continuum of diffuse magnetic
      scattering with a resonancelike gap of ~7  meV and the surprising absence of
      coherent spin waves, suggestive of itinerant magnetism. While the gap closes
      above the Neel temperature, strong dynamic spin correlations persist to a high
      temperature. Nevertheless, the size and temperature dependence of the total
      magnetic spectral weight can be well described by a local moment with J=4.
      Furthermore, polarized neutron measurements reveal that the magnetic fluctuations
      are mostly transverse, with little or none of the longitudinal component expected
      for itinerant moments. These results suggest that a dual description of local and
      itinerant magnetism is required to understand UPt_{2}Si_{2} and, by extension,
      other 5f systems, in general.

PMID- 30118281
TI  - Zeeman Splitting and Inverted Polarization of Biexciton Emission in Monolayer
      WS_{2}.
AB  - Atomically thin semiconductors provide an ideal testbed to investigate the
      physics of Coulomb-bound many-body states. We shed light on the intricate
      structure of such complexes by studying the magnetic-field-induced splitting of
      biexcitons in monolayer WS_{2} using polarization-resolved photoluminescence
      spectroscopy in out-of-plane magnetic fields up to 30 T. The observed g factor of
      the biexciton amounts to about -3.9, closely matching the g factor of the neutral
      exciton. The biexciton emission shows an inverted circular field-induced
      polarization upon linearly polarized excitation; i.e., it exhibits preferential
      emission from the high-energy peak in a magnetic field. This phenomenon is
      explained by taking into account the hybrid configuration of the biexciton
      constituents in momentum space and their respective energetic behavior in
      magnetic fields. Our findings reveal the critical role of dark excitons in the
      composition of this many-body state.

PMID- 30118282
TI  - Ramsey Interferences and Spin Echoes from Electron Spins Inside a Levitating
      Macroscopic Particle.
AB  - We report on observations of Ramsey interferences and spin echoes from electron
      spins inside a levitating macroscopic particle. The experiment is realized using
      nitrogen-vacancy (NV) centers hosted in a micron-sized diamond stored in a Paul
      trap both under atmospheric conditions and under vacuum. Spin echoes are used to
      show that the Paul trap preserves the coherence time of the embedded electron
      spins for more than microseconds. Conversely, the NV spin is employed to
      demonstrate high angular stability of the diamond even under vacuum. These
      results are significant steps towards strong coupling of NV spins to the
      rotational mode of levitating diamonds.

PMID- 30118283
TI  - Universal Scaling Laws in Schottky Heterostructures Based on Two-Dimensional
      Materials.
AB  - We identify a new universality in the carrier transport of two-dimensional (2D)
      material-based Schottky heterostructures. We show that the reversed saturation
      current (J) scales universally with temperature (T) as log(J/T^{beta})?-1/T, with
      beta=3/2 for lateral Schottky heterostructures and beta=1 for vertical Schottky
      heterostructures, over a wide range of 2D systems including nonrelativistic
      electron gas, Rashba spintronic systems, single- and few-layer graphene,
      transition metal dichalcogenides, and thin films of topological solids. Such
      universalities originate from the strong coupling between the thermionic process
      and the in-plane carrier dynamics. Our model resolves some of the conflicting
      results from prior works and is in agreement with recent experiments. The
      universal scaling laws signal the breakdown of beta=2 scaling in the classic
      diode equation widely used over the past sixty years. Our findings shall provide
      a simple analytical scaling for the extraction of the Schottky barrier height in
      2D material-based heterostructures, thus paving the way for both a fundamental
      understanding of nanoscale interface physics and applied device engineering.

PMID- 30118284
TI  - Development of Ferromagnetic Fluctuations in Heavily Overdoped
      (Bi,Pb)_{2}Sr_{2}CuO_{6+delta} Copper Oxides.
AB  - We demonstrate the presence of ferromagnetic (FM) fluctuations in the
      superconducting and nonsuperconducting heavily overdoped regimes of high
      temperature superconducting copper oxides, using (Bi,Pb)_{2}Sr_{2}CuO_{6+delta}
      (Bi-2201) single crystals. Magnetization curves exhibit a tendency to be
      saturated in high magnetic fields at low temperatures in the heavily overdoped
      crystals, which is probably a precursor phenomenon of a FM transition at a lower
      temperature. Muon spin relaxation detects the enhancement of spin fluctuations at
      high temperatures below 200 K. Correspondingly, the ab-plane resistivity follows
      a 4/3 power law in a wide temperature range, which is characteristic of metals
      with two-dimensional FM fluctuations due to itinerant electrons. As the Wilson
      ratio evidences the enhancement of spin fluctuations with hole doping in the
      heavily overdoped regime, it is concluded that two-dimensional FM fluctuations
      reside in the heavily overdoped Bi-2201 cuprates, which is probably related to
      the decrease in the superconducting transition temperature in the heavily
      overdoped cuprates.

PMID- 30118285
TI  - Identification of Antiferromagnetic Domains Via the Optical Magnetoelectric
      Effect.
AB  - The ultimate goal of multiferroic research is the development of a new-generation
      nonvolatile memory devices, where magnetic bits are controlled via electric
      fields with low energy consumption. Here, we demonstrate the optical
      identification of magnetoelectric (ME) antiferromagnetic (AFM) domains in the
      LiCoPO_{4} exploiting the strong absorption difference between the domains. This
      unusual contrast, also present in zero magnetic field, is attributed to the
      dynamic ME effect of the spin-wave excitations, as confirmed by our microscopic
      model, which also captures the characteristics of the observed static ME effect.
      The control and the optical readout of AFM/ME domains, demonstrated here, will
      likely promote the development of ME and spintronic devices based on AFM
      insulators.

PMID- 30118280
TI  - Precision Measurement of Cosmic-Ray Nitrogen and its Primary and Secondary
      Components with the Alpha Magnetic Spectrometer on the International Space
      Station.
AB  - A precision measurement of the nitrogen flux with rigidity (momentum per unit
      charge) from 2.2 GV to 3.3 TV based on 2.2*10^{6} events is presented. The
      detailed rigidity dependence of the nitrogen flux spectral index is presented for
      the first time. The spectral index rapidly hardens at high rigidities and becomes
      identical to the spectral indices of primary He, C, and O cosmic rays above ~700 
      GV. We observed that the nitrogen flux Phi_{N} can be presented as the sum of its
      primary component Phi_{N}^{P} and secondary component Phi_{N}^{S},
      Phi_{N}=Phi_{N}^{P}+Phi_{N}^{S}, and we found Phi_{N} is well described by the
      weighted sum of the oxygen flux Phi_{O} (primary cosmic rays) and the boron flux
      Phi_{B} (secondary cosmic rays), with Phi_{N}^{P}=(0.090+/-0.002)*Phi_{O} and
      Phi_{N}^{S}=(0.62+/-0.02)*Phi_{B} over the entire rigidity range. This
      corresponds to a change of the contribution of the secondary cosmic ray component
      in the nitrogen flux from 70% at a few GV to <30% above 1 TV.

PMID- 30118286
TI  - Testing Quantum Electrodynamics in the Lowest Singlet State of Neutral Beryllium
      9.
AB  - We report spectroscopic results on the 2s2p^{1}P_{1} state in neutral atomic
      beryllium-9. The absolute frequency for the center of gravity is determined to be
      42 565.4501(13)  cm^{-1}, a factor of 130 more precise than the previous
      experimental measurement. The result is in agreement with and a factor of 8 more
      precise than the current best theoretical estimate of 42 565.441(11)  cm^{-1},
      which was calculated including the effects of quantum electrodynamics. Because of
      the large natural linewidth of the transition, the hyperfine constants were not
      able to be extracted to high precision.

PMID- 30118288
TI  - Single Atom Detection from Low Contrast-to-Noise Ratio Electron Microscopy
      Images.
AB  - Single atom detection is of key importance to solving a wide range of scientific
      and technological problems. The strong interaction of electrons with matter makes
      transmission electron microscopy one of the most promising techniques. In
      particular, aberration correction using scanning transmission electron microscopy
      has made a significant step forward toward detecting single atoms. However, to
      overcome radiation damage, related to the use of high-energy electrons, the
      incoming electron dose should be kept low enough. This results in images
      exhibiting a low signal-to-noise ratio and extremely weak contrast, especially
      for light-element nanomaterials. To overcome this problem, a combination of
      physics-based model fitting and the use of a model-order selection method is
      proposed, enabling one to detect single atoms with high reliability.

PMID- 30118289
TI  - Rodlike Counterions near Charged Cylinders: Counterion Condensation and
      Intercylinder Interaction.
AB  - We study a system composed of like-charged cylinders and dumbbell-like
      counterions, with the focus laid on the role of the internal structure of
      counterions, using Monte Carlo simulations. The dumbbell ions are found to
      exhibit novel counterion condensation behavior governed by their length.
      Effective electrostatic interactions mediated between charged parallel cylinders
      also turn out significantly different from the case of pointlike ions, as a
      result of the complex interplay between the spatially separated charge
      distribution in the dumbbell counterions, their orientation, and the curvature of
      the charged cylinder. We show that at a weak-to-moderate electrostatic coupling
      strength, where effective like-charge interactions are usually found to be
      repulsive, the intercylinder interaction can become attractive and display a
      distinctive sensitivity to the cylinder curvature and dumbbell size, proving the
      significant effect of ion structure.

PMID- 30118291
TI  - Quantum Error Correction with Only Two Extra Qubits.
AB  - Noise rates in quantum computing experiments have dropped dramatically, but
      reliable qubits remain precious. Fault-tolerance schemes with minimal qubit
      overhead are therefore essential. We introduce fault-tolerant error-correction
      procedures that use only two extra qubits. The procedures are based on adding
      "flags" to catch the faults that can lead to correlated errors on the data. They
      work for various distance-three codes. In particular, our scheme allows one to
      test the ?5,1,3? code, the smallest error-correcting code, using only seven
      qubits total. Our techniques also apply to the ?7,1,3? and ?15,7,3? Hamming
      codes, thus allowing us to protect seven encoded qubits on a device with only 17
      physical qubits.

PMID- 30118292
TI  - All Local Gauge Invariants for Perturbations of the Kerr Spacetime.
AB  - We present two complex scalar gauge invariants for perturbations of the Kerr
      spacetime defined covariantly in terms of the Killing vectors and the conformal
      Killing-Yano tensor of the background together with the linearized curvature and
      its first derivatives. These invariants are, in particular, sensitive to
      variations of the Kerr parameters. Together with the Teukolsky scalars and the
      linearized Ricci tensor, they form a minimal set that generates all local gauge
      invariants. We also present curvature invariants that reduce to the gauge
      invariants in the linearized theory.

PMID- 30118287
TI  - Observation of Complex Time Structures in the Cosmic-Ray Electron and Positron
      Fluxes with the Alpha Magnetic Spectrometer on the International Space Station.
AB  - We present high-statistics, precision measurements of the detailed time and
      energy dependence of the primary cosmic-ray electron flux and positron flux over
      79 Bartels rotations from May 2011 to May 2017 in the energy range from 1 to 50
      GeV. For the first time, the charge-sign dependent modulation during solar
      maximum has been investigated in detail by leptons alone. Based on 23.5*10^{6}
      events, we report the observation of short-term structures on the timescale of
      months coincident in both the electron flux and the positron flux. These
      structures are not visible in the e^{+}/e^{-} flux ratio. The precision
      measurements across the solar polarity reversal show that the ratio exhibits a
      smooth transition over 830+/-30 days from one value to another. The midpoint of
      the transition shows an energy dependent delay relative to the reversal and
      changes by 260+/-30 days from 1 to 6 GeV.

PMID- 30118290
TI  - Isotensor Dibaryon in the pp->pppi^{+}pi^{-} Reaction?
AB  - Exclusive measurements of the quasifree pp->pppi^{+}pi^{-} reaction have been
      carried out at WASA@COSY by means of pd collisions at T_{p}=1.2  GeV. Total and
      differential cross sections have been extracted covering the energy region
      T_{p}=1.08-1.36  GeV, which is the region of N^{*}(1440) and
      Delta(1232)Delta(1232) resonance excitations. Calculations describing these
      excitations by t-channel meson exchange are at variance with the measured
      differential cross sections and underpredict substantially the experimental total
      cross section. An isotensor DeltaN dibaryon resonance with I(J^{P})=2(1^{+})
      produced associatedly with a pion is able to overcome these deficiencies.

PMID- 30118293
TI  - Universal Nonphononic Density of States in 2D, 3D, and 4D Glasses.
AB  - It is now well established that structural glasses possess disorder- and
      frustration-induced soft quasilocalized excitations, which play key roles in
      various glassy phenomena. Recent work has established that in model glass formers
      in three dimensions, these nonphononic soft excitations may assume the form of
      quasilocalized, harmonic vibrational modes whose frequency follows a universal
      density of states D(omega)~omega^{4}, independently of microscopic details, and
      for a broad range of glass preparation protocols. Here, we further establish the
      universality of the nonphononic density of vibrational modes by direct
      measurements in model structural glasses in two dimensions and four dimensions.
      We also investigate their degree of localization, which is generally weaker in
      lower spatial dimensions, giving rise to a pronounced system-size dependence of
      the nonphononic density of states in two dimensions, but not in higher
      dimensions. Finally, we identify a fundamental glassy frequency scale omega_{c}
      above which the universal omega^{4} law breaks down.

PMID- 30118294
TI  - Time Irreversibility and Criticality in the Motility of a Flagellate
      Microorganism.
AB  - Active living organisms exhibit behavioral variability, partitioning between fast
      and slow dynamics. Such variability may be key to generating rapid responses in a
      heterogeneous, unpredictable environment wherein cellular activity effects
      continual exchanges of energy fluxes. We demonstrate a novel, noninvasive
      strategy for revealing nonequilibrium control of swimming-specifically, in an
      octoflagellate microalga. These organisms exhibit surprising features of
      flagellar excitability and mechanosensitivity, which characterize a novel, time
      irreversible "run-stop-shock" motility comprising forward runs, knee-jerk shocks
      with dramatic beat reversal, and long stops during which cells are quiescent yet
      continue to exhibit submicron flagellar vibrations. Entropy production,
      associated with flux cycles arising in a reaction graph representation of the
      gait-switching dynamics, provides a direct measure of detailed balance violation
      in this primitive alga.

PMID- 30118295
TI  - Defect-Assisted Tunneling Electroresistance in Ferroelectric Tunnel Junctions.
AB  - Recent experimental results have demonstrated ferroelectricity in thin films of
      SrTiO_{3} induced by antisite Ti_{Sr} defects. This opens a possibility to use
      SrTiO_{3} as a barrier layer in ferroelectric tunnel junctions (FTJs)-emerging
      electronic devices promising for applications in nanoelectronics. Here using
      density functional theory combined with quantum-transport calculations applied to
      a prototypical Pt/SrTiO_{3}/Pt FTJ, we demonstrate that the localized in-gap
      energy states produced by the antisite Ti_{Sr} defects are responsible for the
      enhanced electron tunneling conductance which can be controlled by ferroelectric
      polarization. Our tight-binding modeling, which takes into account multiple
      defects, shows that the predicted defect-assisted tunneling electroresistance
      effect is greatly amplified when the defect energy levels are brought to the
      Fermi energy by one of the polarization states. Our results have implications for
      FTJs based on conventional ferroelectric barriers with defects and can be
      employed for the design of new types of FTJs with enhanced performance.

PMID- 30118296
TI  - Time Propagation and Spectroscopy of Fermionic Systems Using a Stochastic
      Technique.
AB  - We present a stochastic method for solving the time-dependent Schrodinger
      equation, generalizing a ground state full configuration interaction quantum
      Monte Carlo method. By performing the time integration in the complex plane close
      to the real-time axis, the numerical effort is kept manageable and the analytic
      continuation to real frequencies is efficient. This allows us to perform ab
      initio calculation of electron spectra for strongly correlated systems. The
      method can be used as a cluster solver for embedding schemes.

PMID- 30118297
TI  - Searching for Near-Horizon Quantum Structures in the Binary Black-Hole Stochastic
      Gravitational-Wave Background.
AB  - Quantum gravity corrections have been speculated to lead to modifications to
      space-time geometry near black-hole horizons. Such structures may reflect
      gravitational waves, causing echoes that follow the main gravitational waves from
      binary black-hole coalescence. By studying two phenomenological models of the
      near-horizon structures under the Schwarzschild approximation, we show that such
      echoes, if they exist, will give rise to a stochastic gravitational-wave
      background, which is very substantial if the near-horizon structure has a near
      unity reflectivity for gravitational waves, readily detectable by Advanced LIGO.
      In case the reflectivity is much less than unity, the background will mainly be
      arising from the first echo, with a level proportional to the power reflectivity
      of the near-horizon structure, but robust against uncertainties in the location
      and the shape of the structure-as long as it is localized and close to the
      horizon. Sensitivity of third-generation detectors allows the detection of a
      background that corresponds to power reflectivity ~3*10^{-3}, if uncertainties in
      the binary black-hole merger rate can be removed. We note that the echoes do
      alter the f^{2/3} power law of the background spectra at low frequencies, which
      is rather robust against uncertainties.

PMID- 30118298
TI  - Photothermal Engineering of Graphene Plasmons.
AB  - Nanoscale photothermal sources find important applications in theranostics,
      imaging, and catalysis. In this context, graphene offers a unique suite of
      optical, electrical, and thermal properties, which we exploit to show self
      consistent active photothermal modulation of its nanoscale response. In
      particular, we predict the existence of plasmons confined to the optical
      landscape tailored by continuous-wave external-light pumping of homogeneous
      graphene. This result relies on the high electron temperatures achievable in
      optically pumped clean graphene while its lattice remains near ambient
      temperature. Our study opens a new avenue toward the active optical control of
      the nanophotonic response in graphene with potential application in photothermal
      devices.

PMID- 30118299
TI  - Inflow Mechanism for Hydrodynamic Entropy.
AB  - We argue that entropy production in hydrodynamics can be understood via a
      superspace inflow mechanism. Our arguments are based on a recently developed
      formalism for constructing effective actions for Schwinger-Keldysh observables in
      quantum field theories. The formalism explicitly incorporates microscopic
      unitarity and the Kubo-Martin-Schwinger thermal periodicity conditions, by
      recasting them in terms of topological Becchi-Rouet-Stora-Tyutin symmetries of
      the effective action.

PMID- 30118300
TI  - Emergence of Weak Coupling at Large Distance in Quantum Gravity.
AB  - The Ooguri-Vafa swampland conjectures claim that in any consistent theory of
      quantum gravity, when venturing to large distances in scalar field space, a tower
      of particles will become light at a rate that is exponential in the field-space
      distance. We provide a novel viewpoint on this claim: If we assume that a tower
      of states becomes light near a particular point in field space, and we further
      demand that loop corrections drive both gravity and the scalar to strong coupling
      at a common energy scale, then the requirement that the particles become light
      exponentially fast in the field-space distance in Planck units follows
      automatically. Furthermore, the same assumption of a common strong-coupling scale
      for scalar fields and gravitons implies that, when a scalar field evolves over a
      super-Planckian distance, the average particle mass changes by an amount of the
      order of the cutoff energy. This supports earlier suggestions that significantly
      super-Planckian excursions in field space cannot be described within a single
      effective field theory. We comment on the relationship of our results to the weak
      gravity conjecture.

PMID- 30118301
TI  - Current-Induced Domain Wall Motion in a Compensated Ferrimagnet.
AB  - Owing to the difficulty in detecting and manipulating the magnetic states of
      antiferromagnetic materials, studying their switching dynamics using electrical
      methods remains a challenging task. By employing heavy-metal-rare-earth
      transition-metal alloy bilayers, we experimentally study current-induced domain
      wall dynamics in an antiferromagnetically coupled system. We show that the
      current-induced domain wall mobility reaches a maximum at the angular momentum
      compensation point. With experiment and modeling, we further reveal the internal
      structures of domain walls and the underlying mechanisms for their fast motion.
      We show that the chirality of the ferrimagnetic domain walls remains the same
      across the compensation points, suggesting that spin orientations of specific
      sublattices rather than net magnetization determine Dzyaloshinskii-Moriya
      interaction in heavy-metal-ferrimagnet bilayers. The high current-induced domain
      wall mobility and the robust domain wall chirality in compensated ferrimagnetic
      material opens new opportunities for high-speed spintronic devices.

PMID- 30118302
TI  - Hierarchy of Azimuthal Anisotropy Harmonics in Collisions of Small Systems from
      the Color Glass Condensate.
AB  - We demonstrate that the striking systematics of two-particle azimuthal Fourier
      harmonics v_{2} and v_{3} in ultrarelativistic collisions of protons, deuterons,
      and helium-3 ions off gold nuclei measured by the PHENIX Collaboration at the
      Relativistic Heavy Ion Collider (RHIC) is reproduced in the color glass
      condensate effective field theory. This contradicts the claim in C. Aidala et al.
      (PHENIX Collaboration), arXiv:1805.02973, that their data rule out initial state
      based explanations. The underlying systematics of the effect, as discussed
      previously in K. Dusling, M. Mace, R. Venugopalan, Phys. Rev. D 97, 016014
      (2018)PRVDAQ2470-001010.1103/PhysRevD.97.016014; Phys. Rev. Lett. 120, 042002
      (2018)PRLTAO0031-900710.1103/PhysRevLett.120.042002; Proc. Sci., QCDEV2017 (2018)
      039, arise from the differing structure of strong color correlations between
      gluon domains of size 1/Q_{S} at fine (p_{?}?Q_{S}) or coarser (p_{?}?Q_{S})
      transverse momentum resolution. Further tests of the limits of validity of this
      framework can be carried out in light-heavy ion collisions at both RHIC and the
      Large Hadron Collider. Such measurements also offer novel opportunities for
      further exploration of the role of the surprisingly large short-range nuclear
      correlations measured at Jefferson Lab.

PMID- 30118303
TI  - Constraining Neutron Capture Cross Sections for Unstable Nuclei with Surrogate
      Reaction Data and Theory.
AB  - Obtaining reliable data for nuclear reactions on unstable isotopes remains an
      extremely important task and a formidable challenge. Neutron capture cross
      sections-crucial ingredients for models of astrophysical processes, national
      security applications, and simulations of nuclear energy generation-are
      particularly elusive, as both projectile and target in the reaction are unstable.
      We demonstrate a new method for determining cross sections for neutron capture on
      unstable isotopes, using ^{87}Y(n,gamma) as a prototype. To validate the method,
      a benchmark experiment is carried out to obtain the known ^{90}Zr(n,gamma) cross
      section analogously. Our approach, which employs an indirect ("surrogate")
      measurement combined with theory, can be generalized to a larger class of nuclear
      reactions. It can be used both with traditional stable-beam experiments and in
      inverse kinematics at rare-isotope facilities.

PMID- 30118304
TI  - Negative-Mass Effects in Spin-Orbit Coupled Bose-Einstein Condensates.
AB  - Negative effective masses can be realized by engineering the dispersion relation
      of a variety of quantum systems. A recent experiment with spin-orbit coupled Bose
      Einstein condensates has shown that a negative effective mass can halt the free
      expansion of the condensate and lead to fringes in the density [M. A. Khamehchi
      et al., Phys. Rev. Lett. 118, 155301 (2017)PRLTAO0031
      900710.1103/PhysRevLett.118.155301]. Here, we show that the underlying cause of
      these observations is the self-interference of the wave packet that arises when
      only one of the two effective mass parameters that characterize the dispersion of
      the system is negative. We show that spin-orbit coupled Bose-Einstein condensates
      may access regimes where both mass parameters controlling the propagation and
      diffusion of the condensate are negative, which leads to the novel phenomenon of
      counterpropagating self-interfering packets.

PMID- 30118305
TI  - Effect of Chain Length Dispersity on the Mobility of Entangled Polymers.
AB  - While nearly all theoretical and computational studies of entangled polymer melts
      have focused on uniform samples, polymer synthesis routes always result in some
      dispersity, albeit narrow, of distribution of molecular weights
      (D_{M}=M_{w}/M_{n}~1.02-1.04). Here, the effects of dispersity on chain mobility
      are studied for entangled, disperse melts using a coarse-grained model for
      polyethylene. Polymer melts with chain lengths set to follow a Schulz-Zimm
      distribution for the same average M_{w}=36  kg/mol with D_{M}=1.0 to 1.16, were
      studied for times of 600-800  MUs using molecular dynamics simulations. This time
      frame is longer than the time required to reach the diffusive regime. We find
      that dispersity in this range does not affect the entanglement time or tube
      diameter. However, while there is negligible difference in the average mobility
      of chains for the uniform distribution D_{M}=1.0 and D_{M}=1.02, the shortest
      chains move significantly faster than the longest ones offering a constraint
      release pathway for the melts for larger D_{M}.

PMID- 30118306
TI  - Experimental Cyclic Interconversion between Coherence and Quantum Correlations.
AB  - Quantum resource theories seek to quantify sources of nonclassicality that bestow
      quantum technologies their operational advantage. Chief among these are studies
      of quantum correlations and quantum coherence. The former isolates
      nonclassicality in the correlations between systems, and the latter captures
      nonclassicality of quantum superpositions within a single physical system. Here,
      we present a scheme that cyclically interconverts between these resources without
      loss. The first stage converts coherence present in an input system into
      correlations with an ancilla. The second stage harnesses these correlations to
      restore coherence on the input system by measurement of the ancilla. We
      experimentally demonstrate this interconversion process using linear optics. Our
      experiment highlights the connection between nonclassicality of correlations and
      nonclassicality within local quantum systems and provides potential flexibilities
      in exploiting one resource to perform tasks normally associated with the other.

PMID- 30118307
TI  - Direct Observation of Incoherent Cherenkov Diffraction Radiation in the Visible
      Range.
AB  - We report on the observation of incoherent Cherenkov radiation emitted by a 5.3
      GeV positron beam circulating in the Cornell electron-positron storage ring as
      the beam passes in the close vicinity of the surface of a fused silica radiator
      (i.e., at a distance larger than 0.8 mm). The shape of the radiator was designed
      in order to send the Cherenkov photons towards the detector, consisting of a
      compact optical system equipped with an intensified camera. The optical system
      allows both the measurements of 2D images and angular distribution including
      polarization study. The corresponding light intensity has been measured as a
      function of the distance between the beam and the surface of the radiator and has
      shown a good agreement with theoretical predictions. For highly relativistic
      particles, a large amount of incoherent radiation is produced in a wide spectral
      range. A light yield of 0.8*10^{-3} photon per particle per turn has been
      measured at a wavelength of 600+/-10  nm in a 2 cm long radiator and for an
      impact parameter of 1 mm. This will find applications in accelerators as
      noninvasive beam diagnostics for both leptons and hadrons.

PMID- 30118308
TI  - High-Harmonic Generation in Mott Insulators.
AB  - Using Floquet dynamical mean-field theory, we study the high-harmonic generation
      in the time-periodic steady states of wide-gap Mott insulators under ac driving.
      In the strong-field regime, the harmonic intensity exhibits multiple plateaus,
      whose cutoff energies epsilon_{cut}=U+mE_{0} scale with the Coulomb interaction U
      and the maximum field strength E_{0}. In this regime, the created doublons and
      holons are localized because of the strong field and the mth plateau originates
      from the recombination of mth nearest-neighbor doublon-holon pairs. In the weak
      field regime, there is only a single plateau in the intensity, which originates
      from the recombination of itinerant doublons and holons. Here,
      epsilon_{cut}=Delta_{gap}+alphaE_{0}, with Delta_{gap} the band gap and alpha>1.
      We demonstrate that the Mott insulator shows a stronger high-harmonic intensity
      than a semiconductor model with the same dispersion as the Mott insulator, even
      if the semiconductor bands are broadened by impurity scattering to mimic the
      incoherent scattering in the Mott insulator.

PMID- 30118309
TI  - Dynamics of Vitrimers: Defects as a Highway to Stress Relaxation.
AB  - We propose a coarse-grained model to investigate stress relaxation in star
      polymer networks induced by dynamic bond-exchange processes. We show how the
      swapping mechanism, once activated, allows the network to reconfigure, exploring
      distinct topological configurations, all of them characterized by complete extent
      of reaction. Our results reveal the important role played by topological defects
      in mediating the exchange reaction and speeding up stress relaxation. The model
      provides a representation of the dynamics in vitrimers, a new class of polymers
      characterized by bond-swap mechanisms which preserve the total number of bonds,
      as well as in other bond-exchange materials.

PMID- 30118310
TI  - Kinetic Signature of Cooperativity in the Irreversible Collapse of a Polymer.
AB  - We investigate the kinetics of a polymer collapse due to the formation of
      irreversible cross-links between its monomers. Using the contact probability P(s)
      as a scale-dependent order parameter depending on the chemical distance s, our
      simulations show the emergence of a cooperative pearling instability. Namely, the
      polymer undergoes a sharp conformational transition to a set of absorbing states
      characterized by a length scale xi corresponding to the mean pearl size. This
      length and the transition time depend on the polymer equilibrium dynamics and the
      cross-linking rate. We confirm experimentally this transition using a DNA
      conformation capture experiment in yeast.

PMID- 30118311
TI  - Synchronizing the Smallest Possible System.
AB  - We investigate the minimal Hilbert-space dimension for a system to be
      synchronized. We first show that qubits cannot be synchronized due to the lack of
      a limit cycle. Moving to larger spin values, we demonstrate that a single spin 1
      can be phase locked to a weak external signal of similar frequency and exhibits
      all the standard features of the theory of synchronization. Our findings rely on
      the Husimi Q representation based on spin coherent states which we propose as a
      tool to obtain a phase portrait.

PMID- 30118312
TI  - Gluon Shadowing in Heavy-Flavor Production at the LHC.
AB  - We study the relevance of experimental data on heavy-flavor [D^{0}, J/psi, B
      >J/psi and Upsilon(1S) mesons] production in proton-lead collisions at the LHC to
      improve our knowledge of the gluon-momentum distribution inside heavy nuclei. We
      observe that the nuclear effects encoded in both most recent global fits of
      nuclear parton densities at next-to-leading order (nCTEQ15 and EPPS16) provide a
      good overall description of the LHC data. We interpret this as a hint that these
      are the dominant ones. In turn, we perform a Bayesian-reweighting analysis for
      each particle data sample which shows that each of the existing heavy
      quark(onium) data set clearly points-with a minimal statistical significance of
      7sigma-to a shadowed gluon distribution at small x in the lead. Moreover, our
      analysis corroborates the existence of gluon antishadowing. Overall, the
      inclusion of such heavy-flavor data in a global fit would significantly reduce
      the uncertainty on the gluon density down to x?7*10^{-6}-where no other data
      exist-while keeping an agreement with the other data of the global fits. Our
      study accounts for the factorization-scale uncertainties which dominate for the
      charm(onium) sector.

PMID- 30118313
TI  - Low-Energy Excitations in Quantum Spin Liquids Identified by Optical
      Spectroscopy.
AB  - The electrodynamic response of organic spin liquids with highly frustrated
      triangular lattices has been measured in a wide energy range. While the overall
      optical spectra of these Mott insulators are governed by transitions between the
      Hubbard bands, distinct in-gap excitations can be identified at low temperatures
      and frequencies, which we attribute to the quantum-spin-liquid state. For the
      strongly correlated beta^{'}-EtMe_{3}Sb[Pd(dmit)_{2}]_{2}, we discover enhanced
      conductivity below 175  cm^{-1}, comparable to the energy of the magnetic
      coupling J~250  K. For omega->0, these low-frequency excitations vanish faster
      than the charge-carrier response subject to Mott-Hubbard correlations, resulting
      in a dome-shaped band peaked at 100  cm^{-1}. Possible relations to spinons,
      magnons, and disorder are discussed.

PMID- 30118315
TI  - Soft Quantum Control for Highly Selective Interactions among Joint Quantum
      Systems.
AB  - We propose a quantum control scheme aimed at interacting systems that gives rise
      to highly selective coupling among their near-to-resonance constituents. Our
      protocol implements temporal control of the interaction strength, switching it on
      and off again adiabatically. This soft temporal modulation significantly
      suppresses off-resonant contributions in the interactions. Among the applications
      of our method we show that it allows us to perform an efficient rotating-wave
      approximation in a wide parameter regime, the elimination of side peaks in
      quantum sensing experiments, and selective high-fidelity entanglement gates on
      nuclear spins with close frequencies. We apply our theory to nitrogen-vacancy
      centers in diamond and demonstrate the possibility for the detection of weak
      electron-nuclear coupling under the presence of strong perturbations.

PMID- 30118316
TI  - Erratum: Microscopic Phase-Space Exploration Modeling of ^{258}Fm Spontaneous
      Fission [Phys. Rev. Lett. 118, 152501 (2017)].
AB  - This corrects the article DOI: 10.1103/PhysRevLett.118.152501.

PMID- 30118317
TI  - Linaclotide Improves Gastrointestinal Transit in Cystic Fibrosis Mice by
      Inhibiting Sodium/Hydrogen Exchanger 3.
AB  - Gastrointestinal dysfunction in Cystic Fibrosis (CF) is a prominent source of
      pain among patients with CF. Linaclotide, a Guanylate Cyclase C (GCC) receptor
      agonist, is an FDA-approved drug prescribed for chronic constipation, but has not
      been widely utilized in CF, as the cystic fibrosis transmembrane conductance
      regulator (CFTR) is the main mechanism of action. However, anecdotal clinical
      evidence suggests that linaclotide may be effective for treating some
      gastrointestinal symptoms in CF. The goal of this study was to determine the
      effectiveness and mechanism of linaclotide in treating CF gastrointestinal
      disorders utilizing CF mouse models. Intestinal transit, chloride secretion, and
      intestinal lumen fluidity was assessed in wildtype and CF mouse models in
      response to linaclotide. CFTR and Sodium/Hydrogen Exchanger 3 (NHE3) response to
      linaclotide was also evaluated. Linaclotide treatment improved intestinal transit
      in mice carrying either F508del or null Cftr mutations but did not induce
      detectable Cl- secretion. Linaclotide increased fluid retention and fluidity of
      CF intestinal contents, suggesting inhibition of fluid absorption. Targeted
      inhibition of sodium absorption by the NHE3 inhibitor tenapanor produced similar
      improvements in gastrointestinal transit as linaclotide treatment, suggesting
      that inhibition of fluid absorption by linaclotide contributes to improved
      gastrointestinal transit in CF. Our results demonstrate that linaclotide improves
      gastrointestinal transit in CF mouse models by increasing luminal fluidity
      through inhibiting NHE3 mediated sodium absorption. Further studies are necessary
      to assess whether linaclotide could improve CF intestinal pathologies in
      patients. GCC signaling and NHE3 inhibition may be therapeutic targets for CF
      intestinal manifestations.

PMID- 30118318
TI  - Reply to Hu et al.: How to Determine the Patient's Head and Neck Posture during
      Computed Tomography Scanning?

PMID- 30118319
TI  - Evaluation of Healing After Medial Meniscal Root Repair Using Second-Look
      Arthroscopy, Clinical, and Radiological Criteria.
AB  - BACKGROUND: Previous studies have reported various healing rates (0%-100%) as
      evaluated by second-look arthroscopy after repair of medial meniscal root tears
      (MMRTs). Such variable results might provoke suspicion of the necessity for
      repair. Furthermore, the effect of meniscal healing on the clinical outcomes has
      not been reported. PURPOSE: To more precisely determine the healing rate of MMRTs
      repaired through the transseptal portal, which could provide objective
      visualization of the healed meniscus, and to identify the effect of meniscal
      healing on the clinical and radiological outcomes. STUDY DESIGN: Case series;
      Level of evidence, 4. METHODS: Between June 2010 and April 2015, 56 patients
      underwent pullout suture for MMRT. Lysholm score, Hospital for Special Surgery
      score, International Knee Documentation Committee subjective score, medial joint
      space height, and Kellgren-Lawrence (K-L) grade were evaluated. Thirty-three
      patients underwent second-look arthroscopy and were divided into a "stable healed
      group" and "unhealed group" according to their healing status, as evaluated
      through the transseptal portal. The intraoperative, clinical, and radiological
      outcomes of the 2 groups were compared. RESULTS: All other clinical outcomes
      improved. However, medial joint space became significantly narrower ( P < .001),
      and 23 patients (41%) showed K-L grade progression. On the basis of second-look
      arthroscopy, 23 patients (69.7%) were classified into a stable healed group and
      10 (30.3%) into a unhealed group. The stable healed group showed a higher
      Hospital for Special Surgery score ( P = .023), International Knee Documentation
      Committee subjective score ( P = .031), and successful microfracture rate ( P =
      .023), with less progression of medial joint space narrowing ( P < .001) and K-L
      grade ( P < .001). CONCLUSION: Despite degenerative change progression, clinical
      outcomes were improved. The successful healing rate was 69.7% after repair of
      MMRTs. Compared with the unhealed group, the stable healed group showed better
      clinical outcomes and less degenerative change progression.

PMID- 30118320
TI  - Buprenorphine in the real world: coming to terms with misuse and diversion.

PMID- 30118321
TI  - Up-regulated miR-192-5p expression rescues cognitive impairment and restores
      neural function in mice with depression via the Fbln2-mediated TGF-beta1
      signaling pathway.
AB  - Depression represents a condition characterized by cognitive deficits and neural
      dysfunction and has recently been correlated with microRNAs (miRs) and their
      respective target genes. The present study was conducted with the goal of
      investigating the expression of miR-192-5p and its target gene fibulin (Fbln)-2
      in an attempt to evaluate their roles in the occurrence and progression of
      cognitive impairment and neural function in mice with chronic unpredictable mild
      stress (CUMS)-induced depression through regulation of the TGF-beta1 signal
      transduction pathway. Verification of the targeting relationship between miR-192
      5p and Fbln2 was provided in the form of initial bioinformatics prediction,
      followed by a further verification in the form of a dual-luciferase reporter gene
      assay. Normal mice and models induced by CUMS were assigned into various groups,
      whereas mimics, inhibitors, and small interfering RNA were introduced to validate
      the regulatory mechanism by which miR-192-5p regulates Fbln2 depression. Novel
      object recognition, tail suspension testing, and Morris water maze were all
      employed 28 d after transfection. Hippocampal electrophysiological recordings,
      Golgi staining, HPLC mass spectrometry, and fluorescence immunohistochemistry
      were performed to further evaluate cognitive function and neuron regeneration.
      CUMS-induced depression was determined to represent a predisposing factor for
      cognitive impairment and damage to neural function in mice, highlighted by novel
      object recognition, learning and memory abilities, population spike amplitude,
      synaptic transmission, cAMP levels, neuronal regeneration, and increased
      behavioral changes that resemble depression. Furthermore, increased Fbln2
      expression, an activated TGF-beta1 signaling pathway, and decreased expression of
      miR-192-5p, synaptophysin, brain-derived neurotrophic factor, N-methyl-d
      aspartate receptor subunit 2B, and calmodulin-dependent protein kinase II were
      noted. Up-regulated miR-192-5p targeting Fbln2 acts to alleviate CUMS-induced
      depression by inhibiting the TGF-beta1 signaling pathway, resulting in the
      enhanced cognitive function in novel object recognition, learning and memory
      ability, population spike amplitude, synaptic transmission, neuron regeneration,
      and alleviation of behavioral symptoms. The central findings of the present study
      indicate that up-regulated levels of miR-192-5p expression act to suppress
      activation of the TGF-beta1 signaling pathway by means of binding to Fbln2,
      thereby ameliorating cognitive impairment and strengthening neural function in a
      mouse model of depression.-Tang, C.-Z., Yang, J.-T., Liu, Q.-H., Wang, Y.-R.,
      Wang, W.-S. Up-regulated miR-192-5p expression rescues cognitive impairment and
      restores neural function in mice with depression via the Fbln2-mediated TGF-beta1
      signaling pathway.

PMID- 30118322
TI  - Neuropilin-1 maintains dimethylarginine dimethylaminohydrolase 1 expression in
      endothelial cells, and contributes to protection from angiotensin II-induced
      hypertension.
AB  - Dimethylarginine dimethylaminohydrolases (DDAHs) are known to degrade asymmetric
      dimethylarginine, an endogenous inhibitor of NOS, and maintain vascular
      homeostasis; however, the regulatory pathways of DDAHs remain unclear. In this
      study, we aimed to define the role of transmembrane glycoprotein neuropilin-1
      (NRP1) in the expression of DDAHs and investigate the potential roles of NRP1 in
      regulation of blood pressure. Short hairpin RNA-mediated knockdown of NRP1
      reduced the level and mRNA stability of DDAH1 but not DDAH2 in HUVECs, whereas
      overexpression of NRP1 increased the mRNA stability of DDAH1. Meanwhile,
      mesenteric arteries and lung vascular endothelial cells of tamoxifen-inducible
      endothelial cell-specific NRP1 knockout mice exhibited decreased expression of
      DDAH1 and slightly increased expression of DDAH2. Mechanistically, the regulation
      of NRP1 on DDAH1 expression is mediated by a posttranscriptional mechanism
      involving miR-219-5p in HUVECs. Although the endothelial cell-specific NRP1
      knockout mice did not exhibit any significant change in blood pressure at the
      basal level, they were more sensitive to low-dose angiotensin II infusion-induced
      increases in blood pressure. Our results show that NRP1 is required for full
      expression of DDAH1 in endothelial cells and that NRP1 contributes to protection
      from low-dose angiotensin II-induced increases in blood pressure.-Wang, Y., Wang,
      E., Zhang, Y., Madamsetty, V. S., Ji, B., Radisky, D. C., Grande, J. P., Misra,
      S., Mukhopadhyay, D. Neuropilin-1 maintains dimethylarginine
      dimethylaminohydrolase 1 expression in endothelial cells, and contributes to
      protection from angiotensin II-induced hypertension.

PMID- 30118323
TI  - A Concept Map of Behavioral Sleep Medicine: Defining the Scope of the Field and
      Strategic Priorities.

PMID- 30118324
TI  - Pneumonia Outcome Measures Modified to Address Concerns about Coding-related
      Biases.

PMID- 30118325
TI  - Communicating Environmental Health Risks with Indigenous Populations: A
      Systematic Literature Review of Current Research and Recommendations for Future
      Studies.
AB  - Indigenous populations are recognized as a group who are potentially vulnerable
      to environmental health hazards due to their intimate relationship with and
      reliance on local environments for aspects of culture, health, and well-being. In
      many circumstances barriers to effective communication and health risk management
      are linked to cultural, economic, and geographic factors. A systematic literature
      review was conducted to consolidate peer-reviewed research on the communication
      of environmental health risks with Indigenous populations. The comprehensive
      literature review procedures included searching databases and key journals that
      represented various fields in communication, environmental health, and Indigenous
      studies. The review yielded a total of 4,469 potential articles and a total of 13
      of these manuscripts met the inclusion criteria. The 13 articles were analyzed to
      identify lessons learned for effective risk communication. Factors that influence
      successful risk communication strategies with Indigenous populations on this
      topic include: (1) developing messages that are congruent with the populations'
      cultural beliefs and understanding of the environment; (2) including Indigenous
      populations in message design and delivery; (3) using credible and trustworthy
      spokespeople in message delivery; (4) identifying and utilizing effective
      communication materials and channels; and (5) ensuring that messages are
      understandable to the target audience. Gaps in the literature include the lack of
      longitudinal studies that empirically measure changes in perception, awareness
      and behavior, as well as a general lack of theory-based research. Results from
      this review provide directions for future work to help guide the development of
      more effective health risk communication research and strategies with Indigenous
      populations.

PMID- 30118326
TI  - Therapeutic potentials of propolis and pollen on biochemical changes in
      reproductive function of L-NAME induced hypertensive male rats.
AB  - BACKGROUND: Hypertension is described as increased blood pressure based on
      changed hemodynamics and associated with an increased oxidative damage to
      reproductive function. This work is to determine therapeutic and protective
      effects of apitherapy products (propolis and pollen) on reproductive functions of
      L-NAME-induced hypertensive male rats. METHODS: Experimental animals were
      indiscriminately separated into four groups of seven rats in each group: (I)
      Control, (II) L-NAME, (III) L-NAME+ propolis and (IV) L-NAME+ pollen. At the end
      of the experimental applications, the rats were decapitated by anesthesia and
      biochemical analyzes were performed on the removed testicular tissues. RESULTS:
      The levels of TOS, NF-kappaB and MDA in the L-NAME group compared to control have
      increased (p < 0.05). The levels of these parameters in L-NAME+ propolis and L
      NAME+ pollen groups compared to the L-NAME group have decreased (p < 0.05). TAS
      levels, PON1 and CAT activities were significantly decreased in testis tissue
      samples in the L-NAME-induced group (p < 0.05). However, these parameters were
      significantly lower in the L-NAME plus propolis and pollen groups (p < 0.05)
      compared with rats administered L-NAME alone (p < 0.05). NO level significantly
      reduced (p < 0.05) in L-NAME group compared with control group. There was no
      statistically significant changes in the NO level of the L-NAME+ propolis group
      compared with the L-NAME-treated group (p > 0.05). CONCLUSION: It has been
      determined that ethanolic extracts of propolis and pollen, which are natural bee
      products in the regulation of rising blood pressure. Propolis or pollen is
      thought to help regulate reproductive function by inhibiting the functioning of
      inflammatory pathways leading to hypertension.

PMID- 30118327
TI  - Comparison of Echocardiographic Parameters Between Healthy Highlanders in Tibet
      and Lowlanders in Beijing.
AB  - Yang, Ying, Duo-Ji Zha-Xi, Wei Mao, Guang Zhi, Bin Feng, and Yun-Dai Chen.
      Comparison of echocardiographic parameters between healthy highlanders in Tibet
      and lowlanders in Beijing. High Alt Med Biol. 19:259-264, 2018.-The hearts of
      highlanders exhibit distinct features compared with the hearts of lowlanders.
      However, previous findings have not been verified in a large-scale Tibetan
      population study. The aim of this study was to present differences in
      echocardiography results among healthy native Tibetans, acclimatized Han
      highlanders, and Han lowlanders at sea level. A total of 1820 healthy Tibetans
      and 224 healthy Han highlanders were drawn from a representative sample of
      residents in Tibet. Echocardiography was performed on each participant at the
      sampled local medical centers. Echocardiographic data from 2332 healthy Han
      lowlanders were obtained from a database of a medical examination center in
      Beijing. Using propensity score matching to balance differences in demographic
      features, we evaluated the effects of altitude and ethnicity in three paired
      comparisons. The results revealed that the great arteries were larger in the Han
      population than in the Tibetan population regardless of altitude (all p < 0.05).
      No differences were found in the right atrium between different altitudes and
      ethnicities. The diameters and thicknesses of the right ventricle (RV) were
      larger in the Tibetans than in the Han lowlanders (i.e., 30.0 mm (26.0, 34.0)
      versus 28.6 mm (25.5, 31.8) for the basal right ventricular linear dimension).
      The left heart in diastole was largest in the Han lowlanders (i.e., 46.3 +/- 3.9
      mm versus 43.0 mm [40.0, 44.0] in Han highlanders and 45.8 mm [43.0, 48.8] versus
      42.0 mm [39.0, 45.0] in Tibetans for the diameter of the left ventricle [LV] at
      end-diastole). Moreover, the interventricular septum was thicker in the high
      altitude population than in the low-altitude population (all p < 0.05). Compared
      with the Tibetans, the Han highlanders exhibited enhanced ventricular functions
      (65.0% [60.0, 69.0] versus 68.0% [63.0, 69.0] for LV ejection fraction and 22.0
      mm [20.0, 26.0] versus 24.0 mm [21.0, 27.0] for tricuspid annular plane systolic
      excursion, both p < 0.05). In conclusion, a small left heart and a large RV may
      be consequences of hypoxic exposure at high altitudes irrespective of ethnic
      origin.

PMID- 30118328
TI  - Case Report of Frostbite with Delay in Evacuation: Field Use of Iloprost Might
      Have Improved the Outcome.
AB  - Irarrazaval, Sebastian, Pablo Besa, Emmanuel Cauchy, Prativa Pandey, and Jorge
      Vergara. Case report of frostbite with delay in evacuation: field use of iloprost
      might have improved the outcome. High Alt Med Biol 00:000-000, 2018. -Frostbite
      is a common injury in high altitude medicine. Intravenous vasodilators have a
      proven efficacy and, recently, have been proposed as a safe outpatient treatment.
      Nevertheless, the lack of availability and consequently delayed application of
      this treatment option can result in poor clinical outcomes for patients. We
      present the case of a 60-year-old Chilean man with severe frostbite injuries
      suffered while climbing Mount Everest. The patient was initially given field
      treatment to the extent permitted by conditions and consensus guidelines.
      Unfortunately, advanced management was delayed, with iloprost administered 75
      hours after the initial injury. The patient also underwent 5 days of hyperbaric
      and analgesic/antibiotic therapies. An early bone scan predicted a poor clinical
      outcome, and five of the patient's fingers, between both hands, were incompletely
      amputated. We present this case to exemplify the importance of advanced in-field
      management of frostbite injuries.

PMID- 30118329
TI  - Reply: Pneumonia Outcome Measures Modified to Address Concerns about Coding
      related Biases.

PMID- 30118330
TI  - Investigational therapies targeting the androgen signaling axis and the androgen
      receptor and in prostate cancer - recent developments and future directions.
AB  - INTRODUCTION: Despite the heterogeneity of prostate cancer (PCa), androgen
      stimulation is fundamental to its development, growth, and lethality. Therefore,
      the blockade of androgen receptor (AR) signaling is critical to controlling the
      disease, even after progression with castrate levels of androgens. Areas covered:
      We review the current understanding of new ways to block the AR, using novel
      antiandrogen inhibitors, which act on different parts of the AR signaling pathway
      in PCa. We also review new approaches, such as the use of poly(ADP-ribose)
      polymerase (PARP) inhibitors, targeting both the AR and the DNA repair pathway,
      potentially adding synergy and improving efficacy and the combination of AR
      inhibitors and immunotherapy. Bipolar androgen therapy (BAT), an innovative
      strategy to target the AR, has shown early evidence of efficacy in PCa is also
      discussed in detail. We highlight some of the key ongoing studies of greatest
      relevance to this topic. Expert commentary: Clinical trials investigating new AR
      targeted therapies should be encouraged in patients with PCa. While it is
      unlikely that one AR inhibitor will produce long-lasting responses in a
      substantial proportion of patients, there is evidence that some strategies, such
      as the BAT could resensitize the AR to antiandrogens, alternating therapies and
      delaying time to progression, maximizing benefit to patients.

PMID- 30118331
TI  - How to Determine the Patient's Head and Neck Posture during Computed Tomography
      Scanning?

PMID- 30118332
TI  - Utility of risk scores to predict adverse events in cardiac lead extraction.
AB  - INTRODUCTION: Increasing device implantations, patient comorbidities, and longer
      life expectancy contribute to an increased need for lead extraction. Even if
      transvenous lead extraction (TLE) is a highly successful procedure, some serious
      procedural complications are reported. In order to identify those patients who
      are at higher risk, risk stratification scores were proposed. Areas covered: The
      major obstacles to lead extractions are represented by the body's response to the
      foreign implanted material and by the following development of fibrotic reaction
      between the lead and the vascular system. Several clinical factors and device
      features are associated with major complications and worse outcomes. Although
      different multiparametric scores predicting the safety and the efficacy of TLE
      procedures were reported, none of these scores were prospective evaluated. Expert
      commentary: A correct risk stratification is needed in order to refer complex
      patients to centers with proven experience and avoid futile procedures.
      Furthermore, the identification of high-risk patients allows to perform the
      extraction procedure in the operating room instead of electrophysiology lab.
      Albeit some risk scores able to predict adverse event in cardiac lead extraction
      were described, there are still several limitations to their use and
      reproducibility.

PMID- 30118333
TI  - Testing for AFP in combination with ultrasound improves early liver cancer
      detection.

PMID- 30118334
TI  - Olaparib tablets for the treatment of germ line BRCA-mutated metastatic breast
      cancer.
AB  - INTRODUCTION: Germ line BRCA mutations (gBRCAm) are diagnosed in approximately 5%
      of unselected breast cancer patients. Olaparib is a new treatment option for
      patients with a gBRCAm who have metastatic HER2-negative breast cancer. Areas
      covered: Olaparib is an oral poly (ADP-ribose) polymerase inhibitor that has been
      shown in phase I-III clinical trials to have single-agent efficacy in breast
      cancer patients with gBRCAm. The recent phase III OlympiAD study demonstrated a
      statistically significant progression-free survival benefit compared with the
      chemotherapy control arm, although an overall survival benefit has not been
      demonstrated. The most common adverse events seen with olaparib include nausea,
      anemia, and vomiting. The most common grade 3 adverse events are anemia and
      neutropenia. Expert commentary: The US FDA-approved olaparib tablets in January
      2018 for the treatment of patients with a gBRCAm and metastatic HER2-negative
      breast cancer. This is a well-tolerated and effective treatment option for this
      patient population, particularly in patients with triple-negative breast cancer
      in which chemotherapy is the only alternative. More data are needed to understand
      the role of olaparib in combination with endocrine therapy, other targeted
      agents, and chemotherapy, as well as sequentially with platinum chemotherapy in
      the metastatic setting.

PMID- 30118335
TI  - Using the MMPI-2 in Forensic Assessment: Response to Criticism About a Case
      Study.

PMID- 30118336
TI  - The advances in therapy of blastic plasmacytoid dendritic cell neoplasm.
AB  - INTRODUCTION: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and
      aggressive myeloid malignancy that contributes to <1% of all hematologic
      neoplasms. Before the introduction of various targeted agents, the therapeutic
      approach was based on regimens used for acute lymphoblastic or myeloid leukemia
      and non-Hodgkin's lymphoma (e.g. hyperCVAD (hyperfractionated cyclophosphamide,
      vincristine, doxorubicin and dexamethasone alternating with high dose
      methotrexate and cytarabine) and CHOP (cyclophosphamide, doxorubicin,
      vincristine, prednisone) -based regimens) followed by allogeneic stem cell
      transplantation for eligible patients. Given that this disease primarily affects
      older patients, there is a significant barrier to using these highly toxic
      regimens, even though these regimens are usually associated with the most durable
      response Areas covered: In this review, we briefly discuss outcomes with the use
      of leukemia-based induction regimens as well as the use of stem cell transplant.
      We also review low-intensity chemotherapeutic regimens. Finally, we will describe
      both preclinical and early clinical data regarding novel targeted strategies for
      treating BPDCN without the use of cytotoxic chemotherapy, with a focus on the use
      of CD123 directed therapy. Expert opinion: While the current standard treatment
      for BPDCN is acute leukemia-based regimen followed by hematopoietic stem cell
      transplantation for transplant-eligible patients, there are very promising
      results for CD123 directed therapies. The future of BPDCN treatment may include
      targeted therapies without the need for cytotoxic chemotherapy.

PMID- 30118337
TI  - Novel biological therapeutic approaches to cutaneous lupus erythematosus.
AB  - INTRODUCTION: Cutaneous lupus erythematosus (CLE) encompasses a spectrum of
      dermatologic manifestations which can occur with or without systemic lupus
      erythematosus (SLE). Treatment of CLE is challenging as the traditional
      treatments are off label and often fail and there is no drug specifically
      approved for CLE. The knowledge gained from the emerging trials on biologic
      therapy in SLE has provided insight into the utility of biologic therapy for CLE.
      Areas covered: An overview is provided on the biological agents studied for CLE
      discussing their immunological target, their efficacy in treating the various CLE
      manifestations and the outcome measures used. Expert opinion: There is a paucity
      of trials dedicated to the biologic treatment of CLE. Several of the described
      biological treatments' efficacy suggests that different clinical phenotypes of
      CLE may require different immunological targeted therapies. Recently published
      and ongoing trials of SLE focusing on novel agents for CLE using the Cutaneous
      Lupus Area and Severity Index (CLASI) as the outcome measure have shown promising
      results. Further trials designed specifically to study the efficacy of biologic
      treatment in CLE subgroups with or without systemic involvement using specific
      metrics for assessing cutaneous involvement are needed and will aid in
      illuminating the role of biologic therapy in CLE.

PMID- 30118338
TI  - The nocebo effect: a clinical challenge in the era of biosimilars.
AB  - INTRODUCTION: The nocebo effect is defined as a negative effect of a
      pharmacological or non-pharmacological medical treatment that is induced by
      patients' expectations, and that is unrelated to the physiological action of the
      treatment. The nocebo effect is an important clinical challenge in the current
      era of biosimilars. Areas covered: This review aims to answer five key questions
      about the nocebo effect, namely to reveal its definition, pathophysiology,
      clinical relevance, contributing factors, and management. Expert commentary: The
      nocebo effect lowers patients' quality of life and negatively affects treatment
      adherence rates in biosimilar-treated patients. It may negatively impact on the
      cost-savings of biosimilars. Health-care providers in charge of biosimilar
      treated patients need to be aware of the nocebo effect and adopt strategies to
      minimize it. They have to be well-informed and confident about the existing
      evidence about biosimilars. A good patient-physician relationship will improve
      patients' acceptance of biosimilars, and limits the risk of inappropriate
      negative bias and the nocebo effect.

PMID- 30118339
TI  - Hypercapnia-induced shear-mediated dilation in the internal carotid artery is
      blunted in healthy older adults.
AB  - This study aimed to elucidate the effect of aging on shear-mediated dilation of
      the common and internal carotid arteries (CCA and ICA, respectively). Hypercapnia
      induced shear-mediated dilation in the CCA and ICA were assessed in ten young
      (5F/5M, 23+/-1 years) and ten older (6F/4M, 68+/-1 years) healthy adults. Shear
      mediated dilation was induced by two levels of hypercapnia (target end-tidal
      carbon dioxide; +5 and +10mmHg from individual baseline value) and was calculated
      as the percent rise in peak diameter from baseline diameter. There were no
      differences in shear-mediated dilation between young and older adults in either
      artery under lower level of hypercapnia (CCA; 2.8+/-0.6 vs. 2.0+/-0.3%, P=0.35,
      ICA; 4.6+/-0.8 vs 3.6+/-0.4%, P=0.37). However, the shear-mediated dilation in
      response to the higher levels of hypercapnia was attenuated in older compared to
      young adults in the ICA (4.5+/-0.5 vs. 7.9+/-1.2%, P<0.01), but not in the CCA
      (3.7+/-0.6 vs. 4.5+/-0.8%, P=0.35). Shear-mediated dilation was significantly
      correlated to the percent change in shear rate in the ICA (Young; r=0.55, P=0.01,
      Older; r=0.49, P=0.03), but not in the CCA in both young and older adults (Young;
      r=-0.30, P=0.90, Older; r=0.16, P=0.50). These data indicate that aging
      attenuates shear-mediated dilation of the ICA in response to higher levels of
      hypercapnia, and shear rate is an important stimulus for hypercapnic vasodilation
      of the ICA in both young and older adults. The current results may provide
      insight into age-related changes in the regulation of cerebral circulation in
      healthy adults.

PMID- 30118340
TI  - Exacerbation of dystrophic cardiomyopathy by phospholamban deficiency-mediated
      chronically increased cardiac Ca2+ cycling in vivo.
AB  - Cardiomyopathy is a significant contributor to morbidity and mortality in
      Duchenne Muscular Dystrophy (DMD). Membrane instability, leading to intracellular
      calcium (Ca2+) mishandling and overload, causes myocyte death and subsequent
      fibrosis in DMD cardiomyopathy. On a cellular level, cardiac myocytes from mdx
      mice have dysregulated Ca2+ handling, including increased resting Ca2+ and slow
      Ca2+ decay, especially evident under stress conditions. Sarco(endo)plasmic
      reticulum Ca2+ ATPase and its regulatory protein phospholamban (PLN) are
      potential therapeutic targets for DMD cardiomyopathy owing to their key role in
      regulating intracellular Ca2+ cycling. We tested the hypothesis that enhanced
      cardiac Ca2+ cycling would remediate cardiomyopathy caused by dystrophin
      deficiency. We used a genetic complementation model approach by crossing
      dystrophin-deficient mdx mice with PLN knockout mice (termed DKO). As expected,
      adult cardiac myocytes isolated from DKO mice exhibited increased contractility
      and faster relaxation associated with increased Ca2+ transient peak height and
      faster Ca2+ decay rate compared to controls. However, in comparison to wild-type,
      mdx and PLNKO animals, DKO mice unexpectedly had reduced in vivo systolic and
      diastolic function measured by echocardiography. Further, Evan's blue dye uptake
      was increased in DKO hearts compared to control, mdx and PLNKO hearts,
      demonstrating increased membrane damage, which subsequently led to increased
      fibrosis in the DKO myocardium in vivo. In conclusion, despite enhanced
      intracellular Ca2+ handling at the myocyte level, DMD cardiomyopathy was
      exacerbated owing to unregulated chronic increases in Ca2+ cycling in DKO mice in
      vivo. These findings have potential important implications for ongoing
      therapeutic strategies for the dystrophic heart.

PMID- 30118341
TI  - Post Stroke Cognitive Impairment and Hippocampal Neurovascular Remodeling: The
      Impact of Diabetes and Sex.
AB  - Diabetes increases the risk and severity of cognitive impairment, especially
      after ischemic stroke. Pathological remodeling of the cerebrovasculature has been
      postulated to contribute to poor neuronal repair and worsened cognitive deficits
      in diabetes. However, little is known about the effect of diabetes on the
      vascularization of hippocampus, a domain critical to memory and learning.
      Therefore we had two aims for this study: 1) to determine the impact of diabetes
      on hippocampal neurovascular remodeling and the resulting cognitive impairment
      after stroke using two models with varying disease severity, and 2) to compare
      the effects of ischemia on hippocampal neurovascular injury in diabetic males and
      females. Stroke was induced by middle cerebral artery occlusion (MCAO) by either
      the suture or embolic method in control and diabetic age-matched male and female
      Wistar rats. Hippocampal neuronal density, vascular architecture, and microglial
      activation as well as cognitive outcomes were measured. Embolic MCAO induced
      greater neuronal degeneration, pathological vascularization, microglial
      activation and cognitive impairment in diabetes as compared to control animals or
      60 min MCAO. While diabetic males had lower neuronal density at baseline,
      diabetic females had more neurodegeneration after stroke. Control animals
      recovered cognitive function by D14 after stroke, diabetic animals showed
      deficits regardless of sex. These results suggest that mechanisms underlying
      cognitive decline in diabetes may differ in males and females and provide further
      insight to the impact of diabetes on stroke severity and post-stroke cognitive
      impairment.

PMID- 30118314
TI  - Measurement of the Lifetime of the Doubly Charmed Baryon Xi_{cc}^{++}.
AB  - The first measurement of the lifetime of the doubly charmed baryon Xi_{cc}^{++}
      is presented, with the signal reconstructed in the final state Lambda_{c}^{+}K^{
      }pi^{+}pi^{+}. The data sample used corresponds to an integrated luminosity of
      1.7  fb^{-1}, collected by the LHCb experiment in proton-proton collisions at a
      center-of-mass energy of 13 TeV. The Xi_{cc}^{++} lifetime is measured to be
      0.256_{-0.022}^{+0.024}(stat)+/-0.014(syst)  ps.

PMID- 30118342
TI  - MMP-2: Is too low as bad as too high in the cardiovascular system?
AB  - Matrix metalloproteinase-2 (MMP-2) cleaves a broad spectrum of substrates
      including extracellular matrix components (responsible for normal tissue
      remodeling) and cytokines (modulators of the inflammatory response to
      physiological insults such as tissue damage). MMP-2 expression is elevated in
      many pathologies (e.g., myocardial infarction, hypertensive heart disease,
      inflammation) where tissue remodeling and inflammatory responses are perturbed.
      Thus, it has generally been assumed that blockade of MMP-2 activity will yield
      therapeutic effects. Here, we provide a counter-argument to this dogma based on:
      a) Preclinical studies on Mmp2 null (Mmp2-/-) mice subjected to myocardial
      infarction, hypertensive heart disease or inflammatory conditions. b) Clinical
      studies on patients with congenital cardiac and bone physiology abnormalities due
      to inactivating MMP2 gene mutations. Furthermore, we put forward the hypothesis
      that when MMP-2 activity falls below baseline the bioavailability of pro
      inflammatory cytokines normally cleaved and inactivated by MMP-2 increases
      leading to production of cytokines and cardiac secretion of phospholipase A2
      activity into circulation which stimulate systemic inflammation that perturbs
      lipid metabolism in target organs. Finally, we suggest that insufficient
      understanding of the consequences of MMP-2 deficiency remains a major factor in
      the failure of MMP-2 inhibitor-based therapeutic approaches. This paucity of
      knowledge precludes our ability to effectively intervene in cardiovascular and
      non-cardiovascular pathologies at the level of MMP-2.

PMID- 30118344
TI  - Mutant voltage-gated sodium channels can exert a dominant-negative effect through
      coupled gating.
AB  - Mutations in voltage-gated sodium channels are linked to several channelopathies
      leading to a wide variety of diseases including cardiac arrhythmias, epilepsy and
      myotonia. We previously demonstrated that Nav1.5 trafficking-deficient mutant
      channels could lead to a dominant-negative effect by impairing trafficking of the
      wild-type (WT) channel. We also reported that voltage-gated sodium channels
      associate as dimers with coupled gating properties. Here, we hypothesized that
      the dominant-negative effect of mutant sodium channels could also occur through
      coupled gating. This was tested using cell surface biotinylation and single
      channel recordings to measure the gating probability and coupled gating of the
      dimers. Co-expression of Nav1.5-L325R with WT channels led to a dominant-negative
      effect as reflected by a 75% reduction in current density. Surprisingly, cell
      surface biotinylation showed that Nav1.5-L325R mutant is capable of trafficking,
      with 40% of Nav1.5-L325R reaching the cell surface when expressed alone.
      Importantly, even though a dominant-negative effect on the sodium current is
      observed when WT and Nav1.5-L325R are expressed together, the total NaV channel
      cell surface expression was not significantly altered compared to WT alone. Thus,
      the trafficking deficiency could not explain the 75% decrease in INa.
      Interestingly, single-channel recordings showed that Nav1.5-L325R exerted a
      dominant-negative effect on the WT at the gating level. Both coupled gating and
      gating probability of the WT:L325R dimers were drastically impaired. We conclude
      that dominant-negative suppression exerted by Nav1.5 mutants can also be caused
      by impairing the WT gating probability, a mechanism resulting from the
      dimerization and coupled gating of voltage-gated sodium channel alpha-subunits.

PMID- 30118343
TI  - Mineralocorticoid Receptor Antagonism Improves Parenchymal Arteriole Dilation Via
      a TRPV4-Dependent Mechanism and Prevents Cognitive Dysfunction in Hypertension.
AB  - Hypertension and mineralocorticoid receptor activation cause cerebral parenchymal
      arteriole remodeling; this can limit cerebral perfusion and contribute to
      cognitive dysfunction. We utilized a mouse model of angiotensin II-induced
      hypertension to test the hypothesis that mineralocorticoid receptor activation
      impairs both TRPV4-mediated dilation of cerebral parenchymal arterioles and
      cognitive function. 16-18-week-old male C57bl/6 mice were treated with
      angiotensin II (800ng/kg/min) +/- the mineralocorticoid receptor antagonist,
      eplerenone (100mg/kg/day) for 4 weeks; sham mice served as controls. Data are
      presented as mean +/- SEM; n=5-14 per group. Eplerenone prevented the increased
      parenchymal arteriole myogenic tone and impaired carbachol-induced (10-9-10
      5mol/L) dilation observed during hypertension. The carbachol-induced dilation was
      endothelium-derived hyperpolarization mediated because it could not be blocked by
      L-NAME (10-5mol/L) and indomethacin (10-4mol/L). We used GSK2193874 (10-7mol/L)
      to confirm that in all groups this dilation was dependent on TRPV4 activation.
      Dilation in response to the TRPV4 agonist GSK1016790A (10-9-10-5mol/L) was also
      reduced in the hypertensive mice and this defect was corrected by eplerenone. In
      the hypertensive and eplerenone treated animals, TRPV4 inhibition reduced
      myogenic tone, an effect that was not observed in arterioles from control
      animals. Eplerenone treatment also improved cognitive function and reduced
      microglia density in the hypertensive mice. These data suggest that the
      mineralocorticoid receptor is a potential therapeutic target to improve
      cerebrovascular function and cognition during hypertension.

PMID- 30118345
TI  - Attenuated forearm vascular conductance responses to rhythmic handgrip in young
      african-american compared to caucasian-american men.
AB  - Previous studies have demonstrated that African-American (AA) individuals have
      heightened vasoconstrictor and reduced vasodilator responses under resting
      conditions, as compared to Caucasian-American (CA) individuals. However,
      potential differences in vascular responses to exercise remain unclear.
      Therefore, we tested the hypothesis that, compared to CA, AA would present an
      attenuated increase in forearm vascular conductance (FVC) during rhythmic
      handgrip exercise. Forearm blood flow (FBF; duplex Doppler ultrasound), and mean
      arterial pressure (MAP; finger photoplethysmography) were measured in healthy
      young CA (N = 10) and AA (N = 10) men during six trials of rhythmic handgrip
      performed at workloads of 4, 8, 12, 16, 20, and 24 kg. FVC (calculated as
      FBF/MAP), FBF, and MAP were similar between groups at rest (FVC: CA: 63 +/- 7 vs.
      AA: 62 +/- 7 mL min-1 100 mmHg-1; P = 0.862). There was an intensity-dependent
      increase in FVC during exercise in both groups; however, AA presented lower FVC
      (interaction P < 0.001) at 8, 12, 16, 20, and 24 kg workloads ( e.g., 24 kg: CA:
      324 +/- 20 vs. AA: 241 +/- 21 mL min-1 100 mmHg-1; P < 0.001). FBF responses to
      exercise were also lower in AA (interaction P < 0.001), whereas MAP responses did
      not differ between groups ( e.g., ?MAP at 24 kg: CA: +19 +/- 2 vs. AA: +19 +/- 2
      mmHg; interaction P = 0.950). These findings indicate lower hyperemic responses
      to rhythmic handgrip exercise in AA men, compared to CA men.

PMID- 30118346
TI  - Genotypic and Phenotypic Characterization of Salmonella Isolated from Fresh
      Ground Meats Obtained from Retail Grocery Stores in the Brookings, South Dakota,
      Area.
AB  - Salmonella is one of the most common foodborne pathogens found in retail fresh
      meat products. The purpose of this study was to characterize the Salmonella that
      is found in common types of fresh ground meats available to consumers in grocery
      stores in the Brookings, South Dakota, area. Salmonella serotypes were detected
      in 50 (19%) of 261 retail fresh ground meat samples, with 2 (2%) of 115 ground
      turkey samples, 6 (14%) of 42 chicken samples, and 42 (40%) of 104 ground pork
      samples testing positive for Salmonella. The Salmonella isolates were sequenced
      using an Illumina MiSeq genome sequencer. The resulting genomic sequences were
      analyzed to determine the serotypes of the isolates and to detect the presence of
      virulence and antibiotic resistance genes. The Salmonella isolated from the
      ground meats belonged to 23 different serotypes. The predominant serotype
      isolated from ground chicken was Enteriditis (5 of 6, 83%). Among the ground pork
      isolates, the most common serotypes were the potential monophasic variant of
      Typhimurium (5 of 42, 12%), Uganda (5 of 42, 12%), Anatum (4 of 42, 10%), Derby
      (3 of 42, 7%), Infantis (3 of 42, 7%), and London (3 of 42, 7%). Among the 45
      Salmonella isolates tested to determine their resistance to common veterinary
      antibiotics, 25 (56%) were found to be susceptible to all 14 antibiotics tested,
      11 (24%) were resistant to 1 antibiotic, 4 (9%) were resistant to 2 antibiotics,
      1 (2%) was resistant to 3 antibiotics, 2 (4%) were resistant to 4 antibiotics, 1
      (2%) was resistant to 8 antibiotics, and 1 (2%) was resistant to 10 antibiotics.
      The most common antibiotic resistances observed in this study were to
      streptomycin (15 of 45, 33%), tetracycline (11 of 45, 24%), and sulfisoxazole (7
      of 45, 16%). The results of phenotypic evaluation of antibiotic resistance
      profiles of Salmonella isolates correlated well with the antibiotic resistance
      genes detected in the genomic sequences of the isolates.

PMID- 30118347
TI  - Microbiological Evaluation of Carcasses of Wild Boar Hunted in a Hill Area of
      Northern Italy.
AB  - This study evaluated the prevalence of potential pathogenic bacteria (mainly
      Campylobacter spp., but also Listeria monocytogenes and Salmonella) in wild boar
      (S us scrofa) and the hygiene of carcasses of wild boar hunted in a hill area of
      northern Italy during a hunting season (October to December). In total, 62
      animals were submitted to microbiological analyses of the tonsils (detection of
      Listeria spp. and Listeria monocytogenes), caecal content (detection of
      Salmonella and Campylobacter spp.), mesenteric lymph glands (detection of
      Salmonella), and carcasses. In addition to analyzing pathogen prevalence and
      carcass hygiene of these animals, we performed an enumeration of total viable
      count (TVC), Enterobacteriaceae, Escherichia coli, coagulase-positive
      staphylococci, and spores of sulfite-reducing clostridia. Influencing factors
      considered were sex, weight, and age of the animals and environmental temperature
      on the day of hunting. A high prevalence was observed for L. monocytogenes in
      tonsils (35.3%) and for Campylobacter spp. in caecal content (51.8%), whereas
      Salmonella enterica strains (mainly serovar Thompson) were only occasionally
      isolated (7% in caecal content and 3.5% in lymph glands). The prevalence of L.
      monocytogenes was influenced by animal age and environmental temperature.
      Campylobacter spp. were the only pathogens detected on the carcasses (16.7%).
      Carcasses were characterized by low levels of contamination: TVC, 3.21 +/- 0.80
      log CFU/cm2, Enterobacteriaceae, 1.32 +/- 0.89 log CFU/cm2; E. coli, 1.31 +/-
      0.93 log CFU/cm2; and occasional detection of low counts of staphylococci and
      clostridia. TVC was positively influenced only by high environmental temperature,
      and higher Enterobacteriaceae counts were detected on heavy male carcasses than
      on females. The results confirmed the potential role of wild boars as reservoirs
      for the most important foodborne pathogens. But a low carcass contamination level
      is achievable if hunters are properly trained about hygienic carcass management
      and slaughtering procedures.

PMID- 30118348
TI  - Aflatoxin Contamination of Dried Insects and Fish in Zambia.
AB  - Dried insects and fish are important sources of income and dietary protein in
      Zambia. Some aflatoxin-producing fungi are entomopathogenic and also colonize
      insects and fish after harvest and processing. Aflatoxins are carcinogenic,
      immune-suppressing mycotoxins that are frequent food contaminants worldwide.
      Several species within Aspergillus section Flavi have been implicated as causal
      agents of aflatoxin contamination of crops in Africa. However, aflatoxin
      producers associated with dried fish and edible insects in Zambia remain unknown,
      and aflatoxin concentrations in these foods have been inadequately evaluated. The
      current study sought to address these data gaps to assess potential human
      vulnerability through the dried fish and edible insect routes of aflatoxin
      exposure. Caterpillars ( n = 97), termites ( n = 4), and dried fish ( n = 66)
      sampled in 2016 and 2017 were assayed for aflatoxin by using lateral flow
      immunochromatography. Average aflatoxin concentrations exceeded regulatory limits
      for Zambia (10 MUg/kg) in the moth Gynanisa maja (11 MUg/kg), the moth
      Gonimbrasia zambesina (Walker) (12 MUg/kg), and the termite Macrotermes falciger
      (Gerstacker) (24 MUg/kg). When samples were subjected to simulated poor storage,
      aflatoxins increased ( P < 0.001) to unsafe levels in caterpillars (mean, 4,800
      MUg/kg) and fish ( Oreochromis) (mean, 23 MUg/kg). The L strain morphotype of A.
      flavus was the most common aflatoxin producer on dried fish (88% of Aspergillus
      section Flavi), termites (68%), and caterpillars (61%), with the exception of
      Gynanisa maja, for which A. parasiticus was the most common (44%). Dried fish and
      insects supported growth (mean, 1.3 * 109 CFU/g) and aflatoxin production (mean,
      63,620 MUg/kg) by previously characterized toxigenic Aspergillus section Flavi
      species, although the extent of growth and aflatoxigenicity depended on specific
      fungus-host combinations. The current study shows the need for proper storage and
      testing of dried insects and fish before consumption as measures to mitigate
      human exposure to aflatoxins through consumption in Zambia.

PMID- 30118349
TI  - Inhibition of autotaxin alleviates inflammation and increases the expression of
      sodium-dependent glucose cotransporter 1 and Na+/H+ exchanger 3 in SAMP1/Fc mice.
AB  - Crohn's disease (CD) is a chronic, relapsing, inflammatory disease that is often
      associated with malnutrition due to inflammation in the small intestine.
      Autotaxin (ATX) is a secreted enzyme that produces extracellular lysophosphatidic
      acid (LPA). Increasing evidence suggests that ATX is upregulated during
      inflammation and inhibition of ATX has been effective in attenuating chronic
      inflammatory conditions, such as arthritis and pulmonary fibrosis. This study is
      aimed to determine whether inhibition of ATX alleviates CD-associated
      inflammation and malnutrition by using SAMP1/Fc mice, a model of CD-like ileitis.
      SAMP1/Fc mice were treated the ATX inhibitor PF-8380 for 4 weeks. Inhibition of
      ATX led to increased weight gain in SAMP1/Fc mice, decreased Th2 cytokine
      expression, including IL-4, IL-5 and IL-13, and attenuated immune cell migration.
      SAMP1/Fc mice have low expression of Na+-dependent glucose transporter 1 (SGLT1),
      suggesting impaired nutrient absorption associated with ileitis. PF-8380
      treatment significantly enhanced SGLT1 expression in SAMP1/Fc mice, which could
      reflex the increased weight changes. However, IL-4 or IL-13 did not alter SGLT1
      expression in Caco-2 cells, ruling out their direct effects on SGLT1 expression.
      Immunofluorescence analysis showed that the expression of sucrase-isomaltase, a
      marker for intestinal epithelial cell differentiation, was decreased in inflamed
      regions of SAMP1/Fc mice, which was partially restored by PF-8380. Moreover,
      expression of Na+/H+ exchanger 3 was also improved by PF-8380, suggesting that
      suppression of inflammation by PF-8380 enhanced epithelial cell differentiation.
      Our study therefore suggests that ATX is a potential target for treating
      intestinal inflammation and restoration of the absorptive function of the
      intestine.

PMID- 30118350
TI  - Neonatal gut and immune maturation is determined more by postnatal age than by
      post-conceptional age in moderately preterm pigs.
AB  - Preterm infants have immature organ functions that predispose them to gut and
      immune disorders. Developmental delays at preterm birth may affect various organs
      differently at term-corrected age. We hypothesized that gut and immune maturation
      in moderately preterm neonates depends more on birth and postnatal factors than
      on advancing post-conceptional age (PCA). Using preterm pigs as models, we
      investigated how gut and immune parameters develop until term-corrected age, and
      how these differ from those in term counterparts. Preterm (n=43, 106 d of
      gestation) and term pigs (n=41, 116 d of gestation) were delivered by caesarean
      section, and euthanized at birth (d 1) or postnatal d 11 (term-corrected age for
      preterm pigs), using identical rearing conditions. Relative to term pigs, preterm
      pigs had lower blood oxygenation, glucose, and cortisol levels, lower gut lactase
      activity, villus height and goblet cell density, and lower blood neutrophil,
      helper-T and cytotoxic-T cell numbers at birth. Despite slower growth in preterm
      pigs, most intestinal and immune parameters increased markedly after birth in
      both groups. However, some parameters remained negatively affected by preterm
      birth until postnatal d 11 (goblet cells, gut permeability, cytotoxic-T cells).
      The colon microbiota showed limited differences between preterm and term pigs at
      this time. At the same PCA, preterm 11 d-old pigs had higher blood leukocyte
      numbers and gut enzyme activities but lower villus height and blood cytotoxic-T
      cell numbers, relative to newborn term pigs. Birth and postnatal factors, not
      advancing PCA, are key determinants of gut and immune maturation in moderately
      preterm neonates.

PMID- 30118351
TI  - Periodontal Therapy Favorably Modulates the Oral-Gut-Hepatic Axis in Cirrhosis.
AB  - Cirrhosis is associated with a systemic pro-inflammatory milieu, endotoxemia and
      gut dysbiosis. The oral cavity could be an additional source of inflammation. We
      aimed to determine the effect of periodontal therapy in cirrhosis through
      evaluating endotoxemia, inflammation, cognition and quality of life (QOL). Age
      matched cirrhotic/non-cirrhotic subjects exhibiting chronic gingivitis and/or
      mild/moderate periodontitis underwent periodontal therapy with follow-up at 30
      days. Saliva/stool for microbial composition and serum for MELD score, endotoxin
      and lipopolysaccharide binding protein (LBP) and immune-inflammatory markers (IL
      1beta, IL-6, histatins 1, 3, 5 and lysozyme) were collected at baseline and day
      30. The cognitive function and QOL were also evaluated similarly. A separate
      group of cirrhotic patients were followed for the same duration without
      periodontal therapy. Cirrhotics, especially those with hepatic encephalopathy
      (HE), demonstrated improved dysbiosis in stool and saliva, and improved
      endotoxin, LBP and salivary/serum inflammatory mediators following periodontal
      therapy. These parameters, which were higher in HE at baseline, became
      statistically similar post-therapy. Pre vs post-therapy QOL and cognition also
      improved in HE patients following oral interventions. On the other hand, LBP and
      endotoxin increased over time in cirrhotics not receiving therapy, rest of the
      parameters, including microbiota remained similar over time in the no-therapy
      group. This proof-of-concept study demonstrates that periodontal therapy in
      cirrhosis, especially in those with HE, is associated with improved oral and gut
      dysbiosis, systemic inflammation, MELD score and cognitive function, which was
      not observed in those who did not receive therapy over the same time-period.

PMID- 30118352
TI  - Absence of leptin signaling allows fat accretion in cystic fibrosis mice.
AB  - Negative energy balance is a prevalent feature of cystic fibrosis (CF).
      Pancreatic insufficiency, elevated energy expenditure, lung disease, and
      malnutrition, all characteristic of CF, contribute to the negative energy balance
      causing low body-growth phenotype. As low body weight and body mass index
      strongly correlate with poor lung health and survival of patients with CF,
      improving energy balance is an important clinical goal (e.g., high-fat diet). CF
      mouse models also exhibit negative energy balance (growth retardation and high
      energy expenditure), independent from exocrine pancreatic insufficiency, lung
      disease, and malnutrition. To improve energy balance through increased caloric
      intake and reduced energy expenditure, we disrupted leptin signaling by crossing
      the db/db leptin receptor allele with mice carrying the R117H Cftr mutation.
      Compared with db/db mice, absence of leptin signaling in CF mice (CF db/db)
      resulted in delayed and moderate hyperphagia with lower de novo lipogenesis and
      lipid deposition, producing only moderately obese CF mice. Greater body length
      was found in db/db mice but not in CF db/db, suggesting CF-dependent effect on
      bone growth. The db/db genotype resulted in lower energy expenditure regardless
      of Cftr genotype leading to obesity. Despite the db/db genotype, the CF genotype
      exhibited high respiratory quotient indicating elevated carbohydrate oxidation,
      thus limiting carbohydrates for lipogenesis. In summary, db/db-linked
      hyperphagia, elevated lipogenesis, and morbid obesity were partially suppressed
      by reduced CFTR activity. CF mice still accrued large amounts of adipose tissue
      in contrast to mice fed a high-fat diet, thus highlighting the importance of
      dietary carbohydrates and not simply fat for energy balance in CF. NEW &
      NOTEWORTHY We show that cystic fibrosis (CF) mice are able to accrue fat under
      conditions of carbohydrate overfeeding, increased lipogenesis, and decreased
      energy expenditure, although length was unaffected. High-fat diet feeding failed
      to improve growth in CF mice. Morbid db/db-like obesity was reduced in CF double
      mutant mice by reduced CFTR activity.

PMID- 30118353
TI  - Tofacitinib for the treatment of psoriasis and psoriatic arthritis.
AB  - INTRODUCTION: Psoriasis and psoriatic arthritis (PsA) are inflammatory immune
      mediated conditions which can cause considerable disability and reduced quality
      of life. Management can be complex as clinical heterogeneity may lead to
      different treatment pathways. Tofacitinib is a novel, oral Janus Kinase (JAK)
      inhibitor with proven efficacy in rheumatoid arthritis. Areas covered: This
      review analyzes recent studies of tofacitinib in psoriatic disease treatment. The
      relevant literature was identified using clinicaltrials.gov, PubMed, and Google
      Scholar. Tofacitinib efficacy was demonstrated in PsA by the OPAL Broaden and
      OPAL Beyond phase-III studies, and received FDA and EMA approval. Tofacitinib was
      superior to placebo for the treatment of moderate-to-severe plaque psoriasis in
      the OPT Pivotal 1 and 2, OPT Retreatment studies, but FDA approval was declined
      for this indication based on issues of clinical efficacy and long-term safety.
      Expert commentary: Tofacitinib is an important oral drug for the treatment of
      PsA. However, the long-term safety data require further evaluation. Tofacitinib
      and other JAK inhibitors show potential to broaden the treatment options in PsA
      and other inflammatory conditions.

PMID- 30118354
TI  - Clinical management of rheumatologic conditions co-occurring with inflammatory
      bowel diseases.
AB  - INTRODUCTION: Spondyloarthritis (SpA) is the most common extra-intestinal
      manifestation in patients with inflammatory bowel diseases (IBD). Articular
      disorders may also appear as 'paradoxical' effects during biologic therapy with
      anti-tumor necrosis factor (TNF). Areas covered: In this narrative review, we
      report the current knowledge about the pathogenesis, the diagnosis and the
      therapeutic management of articular diseases occurring in patients with IBD.
      Expert commentary: Evidence-based recommendations for the management of IBD
      associated SpA and paradoxical arthritis are lacking. Then, collaboration between
      gastroenterologists and rheumatologists is mandatory to guarantee the best
      outcomes for these patients, from a prompt diagnosis to an appropriate
      therapeutic strategy. Among therapies currently available, steroids,
      sulfasalazine, methotrexate and anti-TNFs are recommended for both
      gastrointestinal and articular diseases, whereas non-steroidal anti-inflammatory
      drugs (NSAIDs) and etanercept are contraindicated in IBD. Thiopurines are not
      effective for the treatment of articular symptoms. Several agents have been
      recently introduced for the treatment of IBD, such as vedolizumab, a gut
      selective anti-alpha4beta7integrin, and ustekinumab, an anti-interleukin 12/23.
      Their effects on SpA still need to be clarified; however, the possible
      contemporary administration of biologics with different molecular targets is
      becoming an intriguing option to cover multiple inflammatory manifestations in
      the same patient and is worthy of further investigation.

PMID- 30118355
TI  - Acquired partial lipodystrophy treated with poly-L-lactic acid and hyaluronic
      acid fillers: a case report.
AB  - Acquired partial lipodystrophy (APL), also known as Barraquer-Simons syndrome, is
      a rare disorder characterized by progressive fat loss in the upper body. Use of
      poly-L-lactic acid and hyaluronic acid (HA) fillers for the treatment of APL is
      neither approved by the Food and Drug Administration nor described in the
      literature. Herein, we describe a case of APL that achieved significant
      improvement in facial volume following treatment with combination poly-L-lactic
      acid and HA fillers.

PMID- 30118356
TI  - Bathroom Entrapment Leading to Cardiac Arrest From Crush Syndrome.
AB  - Crush injuries have the potential to cause life-threatening systemic effects such
      as hyperkalemia, dysrhythmias, acute kidney injury, and renal failure. Systemic
      involvement is known as crush syndrome (CS) and results from tissue ischemia and
      muscle necrosis. This is a report of a 76-year-old female who developed a fatal
      dysrhythmia following release of her extremity from prolonged entrapment in
      bathroom safety equipment. Hyperkalemia should be presumed in any crush injury
      and be treated empirically and aggressively. Although tourniquet application
      prior to extrication is not widely recommended to prevent CS, it should be
      considered in prolonged extremity entrapment.

PMID- 30118357
TI  - Assessment of Key Health and Wellness Indicators Among North Carolina Emergency
      Medical Service Providers.
AB  - OBJECTIVE: The objective of this study was to characterize key health indicators
      in Emergency Medical Services (EMS) personnel and identify areas for intervention
      in order to ensure a strong and capable emergency health workforce. METHODS:
      Participants were EMS personnel delivering patients to 4 regional tertiary care
      emergency departments within North Carolina (NC). After transferring patient care
      and agreeing to participate, height, weight, and blood pressure (BP) measurements
      were recorded and each participant completed a questionnaire regarding
      demographics, activity levels, alcohol consumption, smoking, and medical history.
      Data were analyzed descriptively. RESULTS: A sample of 452 EMS personnel from
      across NC was enrolled. The cohort was predominantly male (74.1%) and employed
      full-time (85.5%). The prevalence of overweight and obesity (80.3%) among EMS
      personnel was higher than the NC population (65.6%) and the general United States
      (US) population (70.8%). A previous diagnosis of high BP was reported by only
      18.3% of participants, but 65.1% had elevated BP at the time of measurement.
      Alcohol consumption in the past 30 days among participants (55.4%) was slightly
      higher than state estimates (48.0%) and similar to national estimates (57.1%).
      However, heavy drinking (22.2%) and binge drinking (28.8%) were reported at much
      higher rates than state (5.6% and 15.2%, respectively) and national (6.6% and
      18.3%, respectively) estimates. The prevalence of current smoking (21.5%) and
      quit attempts (48.8%) in the cohort was similar to state (21.8% and 55.0%,
      respectively) and national (21.2% and 55.7%, respectively) estimates. Likewise,
      the proportion of EMS providers meeting the Center for Disease Control's activity
      guidelines (49.6%) was similar to that found in the NC (46.8%) and the general US
      (48.0%) populations. CONCLUSIONS: These findings suggest a high prevalence of
      overweight and obesity, heavy drinking, binge drinking, and high BP among NC EMS
      personnel. Similar to fire service personnel, these rates are higher than the
      general US population. As such, they suggest areas where intervention would have
      the greatest positive impact on the health and performance of the EMS workforce.

PMID- 30118358
TI  - Emergency Medical Services Response to Mass Shooting and Active Shooter
      Incidents, United States, 2014-2015.
AB  - BACKGROUND: The purpose of the current study was to describe the injury patterns,
      EMS response and interventions to mass shooting (MS) and active shooter (AS)
      incidents. METHODS: Retrospective analysis of 2014-2015 National Emergency
      Medical Services Information System (NEMSIS) data sets. Date, time, and location
      for MS incidents were obtained from the Gun Violence Archive and then correlated
      with NEMSIS data set records. AS incidents were identified through Federal Bureau
      of Investigation (FBI) data. A de-identified database was generated for final
      analysis. RESULTS: A total of 608 MS incidents were identified, of which 19 were
      also classified as AS incidents. NEMSIS patient care data was available for 652
      EMS activations representing 226 unique MS incidents. Thirty-four EMS responses
      to 5 unique AS incidents were similarly identified: 76% of victims were male and
      80% of victims were African American. Dispatch complaint did not suggest shooting
      (potentially dangerous scene environment) in 15.9% of records. The most commonly
      reported incident locations for MS were Street/Highway (38.2%) and Home/Residence
      (32.4%). Location of wounds included extremities (49%), chest (12%), and
      head/neck (13%). Tourniquet use was documented in 6 victims. 35.9% of victims
      were transported to the closest facility. CONCLUSIONS: MS and AS incidents are
      prevalent in the United States. Despite the fact that extremity wounds were
      common, documented EMS tourniquet use was uncommon. While MS events are high risk
      for responders, dispatch information was lacking in almost 15% of records.
      Responding EMS agencies were diverse, emphasizing the need to ensure all EMS
      providers are prepared to respond to MS incidents.

PMID- 30118359
TI  - Seasonal Variation in Human Adenovirus Conjunctivitis: A 30-Year Observational
      Study.
AB  - PURPOSE: The aim of this study is to measure the seasonal trends of adenovirus
      conjunctivitis. METHODS: A total of 926 positive cases of HAdV conjunctivitis
      were reviewed at the University of Pittsburgh Medical Center (UPMC) in Pittsburgh
      (Allegheny County, Pennsylvania, USA) from 11th March 1987 to 15th December 2016.
      To determine seasonal variation, daily counts were adjusted for yearly changes in
      Allegheny County population size, modelled as a function of long-term trend using
      Basis-spline (B-spline), and analysed for seasonal trend by quarter (1Q = January
      to March, 2Q = April to June, 3Q = July to September, 4Q = October to December).
      RESULTS: The number of adenovirus conjunctivitis cases in 3Q was 45% higher than
      that of 2Q (95% confidence interval [CI] 1.21-1.74, P = 0.0001). When 3Q is
      compared to 1Q and 4Q, it was not statistically significant (95% CI 0.96-1.42, P
      = 0.1209 and 95% CI 0.96-1.41, P = 0.1180, respectively). CONCLUSION: To the best
      of our knowledge, this is the first report and the longest time-series evaluating
      the potential seasonality of adenovirus conjunctivitis in the USA. We observed
      the highest number of cases from July to September and the lowest number of cases
      from April to June in our study population. Knowledge of seasonality can be used
      to guide outbreak expectations, limit antibiotic over-prescription, and enhance
      disease prevention.

PMID- 30118360
TI  - Outcomes of Prehospital Chemical Sedation With Ketamine Versus Haloperidol and
      Benzodiazepine or Physical Restraint Only.
AB  - OBJECTIVE: The goal of this study is to describe complications and outcomes of
      prehospital ketamine use for agitation as compared to other methods of physical
      or chemical restraint such as haloperidol plus benzodiazepine or physical
      restraint only. METHODS: We conducted a single-center retrospective review of
      patient encounters in which restraint was administered in the prehospital
      setting. At the beginning of our study window, only physical restraint was
      available to paramedics managing agitated patients but subsequently, haloperidol
      and benzodiazepines were introduced, followed by ketamine 2 years later. By
      comparing patients before and after each transition, we divided subjects into 3
      cohorts based on restraint type: physical restraint, haloperidol plus
      benzodiazepine, and ketamine. Demographic data were collected, and outcome
      measures included intubation rate, need for additional physical or chemical
      restraint, emergency department (ED) length of stay, need for hospital admission,
      and employee injury. RESULTS: Of 214 subjects included in the study, 95 patients
      were administered ketamine, 68 received haloperidol and benzodiazepine, and 51
      were physically restrained. Eleven of the patients (11.6%) who received ketamine
      were intubated. Compared to patients who received haloperidol plus
      benzodiazepine, patients who received ketamine were more likely to be intubated
      (odds ratio [OR] = 8.77, 95% confidence interval [CI], 1.10-69.68) and were more
      likely to require additional chemical restraint when compared to
      haloperidol/benzodiazepine or physical restraint only (OR =2.94, 95% CI, 1.49
      5.80, and OR =2.15, 95% CI, 1.07-4.31, respectively). There were no differences
      between the 2 chemical sedation groups in terms of ED length of stay or hospital
      admission rate. CONCLUSIONS: This study demonstrates a lower intubation rate in
      patients administered ketamine than prior literature in association with a lower
      weight-based dosing regimen. Ketamine use was correlated with a higher frequency
      of intubation and a greater need for additional chemical restraint when compared
      with other restraint modalities, though exogenous factors such as provider
      preference may have impacted this result. There was no difference in ED length of
      stay or admission rate between the ketamine and haloperidol plus benzodiazepine
      groups. Further prospective study is needed to determine whether there is a
      subset of patients for whom ketamine would be beneficial compared to other
      therapies.

PMID- 30118361
TI  - Can Mobile Integrated Health Care Paramedics Safely Conduct Medical Clearance of
      Behavioral Health Patients in a Pilot Project? A Report of the First 1000
      Consecutive Encounters.
AB  - BACKGROUND: Mental health patients wait lengthy periods in emergency departments
      for disposition. This delay is secondary to the process of medical clearance and
      then placement in an appropriate psychiatric specialty center. ACEP clinical
      policy questions the necessity of laboratory investigation for medical clearance
      and favors history and physical exam to determine safe disposition to mental
      health facilities. This manuscript explores if specially trained paramedics can
      effectively employ triage algorithms to determine proper disposition of patients
      suffering an acute mental health crisis in a 9-1-1 system. METHODS: Six
      paramedics working for AMR in Stanislaus County, California underwent 180 hours
      of specialized training to become Mobile Integrated Healthcare Paramedics
      (MIHPs). Their training detailed the use of two algorithms designed to identify
      patients that require evaluation in an emergency department versus those that can
      be triaged directly to a licensed mental health facility. Patients aged 18-59
      with a suspected mental health crisis who are encountered via the 9-1-1 system,
      law enforcement or who walk in to the mental health facility for treatment were
      eligible. All patients in the study were evaluated with the well person algorithm
      (WPA). Those that passed the WPA were evaluated using the mental health clearance
      algorithm (MCHA). MIHPs directed patients to either the ED or the mental health
      facility based upon the evaluation results of the WPA and MHCA. RESULTS: 1006
      patients were evaluated between September 2015 and December 2017. 404 patients
      failed one or more components of the WPA or MHCA. 326 patients passed both the
      WPA and the MHCA, but were ultimately transported to a local emergency
      department, most often because of lack of available psychiatric beds in the
      community. 276 patients were transported directly to a psychiatric facility. Of
      these, 10 returned to the emergency department within 6 hours, but none of the 10
      were admitted for a previously unidentified medical or traumatic condition.
      CONCLUSION: Specially trained paramedics can effectively employ triage algorithms
      to screen and select patients experiencing an acute mental health crisis for
      transport directly to psychiatric treatment facilities.

PMID- 30118362
TI  - Relative Mortality Analysis Of The "Golden Hour": A Comprehensive Acuity
      Stratification Approach To Address Disagreement In Current Literature.
AB  - OBJECTIVE: This study sought to address the disagreement in literature regarding
      the "golden hour" in trauma by using the Relative Mortality Analysis to overcome
      previous studies' limitations in accounting for acuity when evaluating the impact
      of prehospital time on mortality. METHODS: The previous studies that failed to
      support the "golden hour" suffered from limitations in their efforts to account
      for the confounding effects of patient acuity on the relationship between
      prehospital time and mortality in their trauma populations. The Relative
      Mortality Analysis was designed to directly address these limitations using a
      novel acuity stratification approach, based on patients' probability of survival
      (PoS), a comprehensive triage metric calculated using Trauma and Injury Severity
      Score methodology. For this analysis, the population selection and analysis
      methods of these previous studies were compared to the Relative Mortality
      Analysis on how they capture the relationship between prehospital time and
      mortality in the University of Virginia (UVA) Trauma Center population. RESULTS:
      The methods of the previous studies that failed to support the "golden hour" also
      failed to do so when applied to the UVA Trauma Center population. However, when
      applied to the same population, the Relative Mortality Analysis identified a
      subgroup, 9.9% (with a PoS 23%-91%), of the 5,063 patient population with
      significantly lower mortality when transported to the hospital within 1 hour,
      supporting the "golden hour." CONCLUSION: These results suggest that previous
      studies failed to support the "golden hour" not due to a lack of patients
      significantly impacted by prehospital time within their trauma populations, but
      instead due to limitations in their efforts to account for patient acuity. As a
      result, these studies inappropriately rejected the "golden hour," leading to the
      current disagreement in literature regarding the relationship between prehospital
      time and trauma patient mortality. The Relative Mortality Analysis was shown to
      overcome the limitations of these studies and demonstrated that the "golden hour"
      was significant for patients who were not low acuity (PoS >91%) or severely high
      acuity (PoS <23%).

PMID- 30118363
TI  - Comparison of Three Junctional Tourniquets Using a Randomized Trial Design.
AB  - BACKGROUND: Hemorrhage remains a leading cause of death in both civilian and
      military settings. Of preventable deaths from hemorrhage, a significant portion
      occurs from junctional wounds that are not amenable to traditional extremity
      tourniquets. Junctional tourniquets (JTQs) can potentially provide hemorrhage
      control by compressing the arteries at the junction of the trunk and extremities.
      The FDA has cleared 3 JTQ products: The Combat Ready Clamp (CRoC(r)), the
      Junctional Emergency Treatment Tool (JETTTM), and the SAM(r) Junctional
      Tourniquet (SJT). However, little is known regarding which of these JTQs is
      superior in application time, effectiveness in pulse elimination, effectiveness
      during transport, and user preference. METHODS: Active duty corpsmen (N = 49)
      were given standardized instruction and hands-on training with the CRoC(r),
      JETTTM, and SJT, then sequentially applied each JTQ unilaterally to a fellow
      study participant in a randomized order. Pulse elimination was determined by
      Doppler ultrasound at the dorsalis pedis immediately then reevaluated after a
      short transport. User preference data were collected following testing. Data were
      analyzed using repeated measures ANOVA and non-parametric statistics at p < 0.05.
      RESULTS: The CRoC(r) was significantly slower in application time than the JETTTM
      and SJT. Effectiveness was similar for CRoC(r), JETTTM, and SJT. Effectiveness
      during transport was significantly higher for SJT than for the JETTTM, but no JTQ
      performed well during transport (24-48% effectiveness). SJT ranked first in
      perceived ease of use, stability, and reliability, and in user trust and overall
      preference. Participants provided cogent suggestions for product improvement.
      CONCLUSIONS: All JTQ devices performed poorly during transport. Combined, present
      findings highlight the potential of JTQ products for saving lives threatened by
      junctional wounds, but also highlight the need for specific product improvements
      towards fostering JTQ performance in patient transport.

PMID- 30118364
TI  - Association of Pregnancy History and Cervical Cancer Screening in a Community
      Sample of Sexual Minority Women.
AB  - BACKGROUND: Sexual minority women (SMW) face barriers to healthcare that may
      result in lower utilization of cervical cancer screening. Previous experiences
      with the healthcare system-specifically reproductive health-related encounters
      have the potential to affect future use of screening services. This study aimed
      to examine the association between pregnancy history and cervical cancer
      screening in a diverse sample of SMW. Anderson's Behavioral Model of Health
      Services Use guided the selection of variables included in the study. METHODS: We
      performed a secondary analysis of cross-sectional data from the third wave of the
      Chicago Health and Life Experiences of Women (CHLEW) Study, a longitudinal study
      of SMW in the Midwestern United States. We performed multivariable logistic
      regression to address the study aims, restricting the sample to women ages 21-45
      (n = 430). RESULTS: Reporting a previous pregnancy was consistently positively
      associated with past-year Pap testing. In the multivariable model, bisexual
      identity and disclosing one's sexual orientation to healthcare providers were
      also positively associated with past-year Pap test. CONCLUSIONS: This analysis
      provides preliminary evidence that SMW who have been pregnant are more likely to
      receive Pap testing and that multiple sociodemographic factors are likely to
      impact screening in this population. Clinicians should screen all patients with a
      cervix for cervical cancer and should encourage screening for all SMW. Future
      studies should prioritize longitudinal analyses to examine the temporality of
      reproductive history and healthcare seeking, focus on where SMW seek care, and
      understand how intersecting components of identity may shape the healthcare
      utilization of this population.

PMID- 30118365
TI  - Challenges of Burn Mass Casualty Incidents in the Prehospital Setting: Lessons
      From the Formosa Fun Coast Park Color Party.
AB  - OBJECTIVE: A burn mass casualty incident (BMCI) involving 499 patients occurred
      at a "color party" in Taiwan in June 27, 2015. We implemented a study to identify
      critical challenges regarding the prehospital emergency care in BMCIs. METHODS: A
      3-stage, mixed methods study was conducted in 2016. First, a statistical analysis
      of prehospital management using the data retrieved from the Emergency Medical
      Management System of the Ministry of Health and Welfare, Taiwan was performed.
      This was followed by a face-to-face, open-ended interview with the emergency
      medical technicians and the staff of the emergency operations center who
      responded to the incident; and the transcription of the interview data into
      constructed themes. RESULTS: Our study indicated that the signs of inhalation
      injury needed to be incorporated in the field triage protocol for BMCIs; the
      collaborative utilization of regional emergency medical services may improve the
      surge capacity in the field; and an "island-hopping" strategy for patient
      transportation may allow the healthcare systems to manage the surge of burn
      patients more efficiently. CONCLUSIONS: Current field triage protocols may be
      insufficient for burn patients and should be further investigated. The practices
      in field triage, transport capacity, and transfer strategy can be considered as a
      part of an efficient prehospital emergency response to BMCIs.

PMID- 30118366
TI  - Perceptions by Families of Emergency Medical Service Interventions During
      Imminent Pediatric Out-of-Hospital Death.
AB  - OBJECTIVE: To understand how family members view the ways Emergency Medical
      Services (EMS) and other first responders interact with distressed family members
      during an intervention involving a recent or impending pediatric death. METHODS:
      In depth interviews with 11 grieving parents of young children and survey results
      from 4 additional grieving parents of adult children were conducted as part of a
      larger study on effective ways for EMS providers to interact with distressed
      family members during a pediatric death in the field. The responses were analyzed
      using qualitative content analyses. RESULTS: Family reactions to the crisis and
      the professional response by first responders were critical to family coping and
      getting necessary support. There were several critical competencies identified to
      help the family cope including: (1) that first responders provide excellent and
      expeditious care with seamless coordination, (2) allowing family to witness the
      resuscitation including the attempts to save the child's life, and (3) providing
      ongoing communication. Whether the child is removed from the scene or not,
      keeping the family apprised of what is happening and why is critical. Giving
      tangible forms of support by calling friends, family, and clergy, along with
      allowing the family time with the child after death, giving emotional support,
      and follow-up gestures all help families cope. CONCLUSION: The study generated
      hypothetical ways for first responders to interact with distressed family members
      during an OOH pediatric death.

PMID- 30118367
TI  - Challenges in Statewide Implementation of a Prehospital Evidence-Based Guideline:
      An Assessment of Barriers and Enablers in Five States.
AB  - BACKGROUND: Individual states, regions, and local emergency medical service (EMS)
      agencies are responsible for the development and implementation of prehospital
      patient care protocols. Many states lack model prehospital guidelines for
      managing common conditions. Recently developed national evidence-based guidelines
      (EBGs) may address this gap. Barriers to statewide dissemination and
      implementation of model guidelines have not been studied. The objective of this
      study was to examine barriers and enablers to dissemination and implementation of
      an evidence-based guideline for traumatic pain management across 5 states.
      METHODS: This study used mixed methods to evaluate the statewide dissemination
      and implementation of a prehospital EBG. The guideline provided pain assessment
      tools, recommended opiate medication dosing, and indications and
      contraindications for analgesia. Participating states were provided an
      implementation toolkit, standardized training materials, and a state-specific
      implementation plan. Outcomes were assessed via an electronic self-assessment
      tool in which states reported barriers and enablers to dissemination and
      implementation and information about changes in pain management practices in
      their states after implementation of the EBG. RESULTS: Of the 5 participating
      states, 3 reported dissemination of the guideline, one through a state model
      guideline process and 2 through regional EMS systems. Two states did not
      disseminate or implement the guideline. Of these, one state chose to utilize a
      locally developed guideline, and the other state did not perform guideline
      dissemination at the state level. Barriers to state implementation were the lack
      of authority at the state level to mandate protocols, technical challenges with
      learning management systems, and inability to track and monitor training and
      implementation at the agency level. Enablers included having a state/regional EMS
      office champion and the availability of an implementation toolkit. No
      participating states demonstrated an increase in opioid delivery to patients
      during the study period. CONCLUSION: Statewide dissemination and implementation
      of an EBG is complex with many challenges. Future efforts should consider the
      advantages of having statewide model or mandatory guidelines and the value of
      local champions and be aware of the challenges of a statewide learning management
      system and of tracking the success of implementation efforts.

PMID- 30118368
TI  - The role of CaMKII in Neuropathic Pain and Fear Memory in Chronic Constriction
      Injury in Rats.
AB  - In this study, we sought to observe the effects of Ca2+/calmodulin-dependent
      protein kinase II (CaMKII) on neuropathic pain and fear memory in a rat model of
      chronic constriction injury (CCI). Rats were randomly divided into the Sham,
      Control, CCI and m-AIP groups. In the m-AIP group, an intrathecal injection of m
      AIP, the specific antagonist of CaMKII, was given either pretreatment or
      posttreatment in rats. Mechanical allodynia and thermal hyperalgesia tests were
      used to test pain behavior, and the passive avoidance test was used to measure
      fear memory in rats. The right side of hippocampus tissues were taken at varying
      time points. The expression levels of CaMKII-alpha, pCaMKII-alpha, CaMKII-beta,
      pCaMKII-beta, NR2A, pNR2A, NR2B and pNR2B were detected by Western blot analysis.
      Significant pain behaviors and impaired cognitive function were shown after CCI
      surgery, accompanied by the upregulation of proteins in the hippocampus.
      Pretreatment with m-AIP appeared to provide a temporary improvement in pain and
      fear memory and decreased the expression of the above proteins in the hippocampus
      seven days after surgery. Furthermore, postoperative treatment with m-AIP
      provided relief for pain behavior and protein expression but did not affect fear
      memory. These data suggested that CaMKII played an important role in the
      crosstalk between neuropathic pain and fear memory, indicating that CaMKII may be
      a potential therapeutic target for neuropathic pain treatment.

PMID- 30118369
TI  - Correlation Between the Revised Trauma Score and Injury Severity Score:
      Implications for Prehospital Trauma Triage.
AB  - OBJECTIVE: Prehospital triage of the seriously injured patient is fraught with
      challenges, and trauma scoring systems in current triage guidelines warrant
      further investigation. The primary objective of this study was to assess the
      correlation of the physiologically based Revised Trauma Score (RTS) and MGAP
      score (mechanism of injury, Glasgow Coma Scale, age, blood pressure) with the
      anatomically based Injury Severity Score (ISS). The secondary objectives for this
      study were to compare the accuracy of the MGAP score and the RTS for the
      prediction of in-hospital mortality for trauma patients. METHODS: This study was
      a retrospective cohort including 10 years of patient data in a large single
      center trauma registry at a primary adult resource center (Level I) for trauma
      patients. Participants included adults (age >=18 years). The primary outcome
      measure was injury severity (measured by ISS) and a secondary analysis compared
      the RTS and MGAP for the prediction of patient mortality. Descriptive statistics
      were used to describe the cohort and correlation methods were employed. Each
      score's accuracy for the prediction of mortality was calculated using the area
      under receiver operating characteristic (AUROC) curves. RESULTS: In total, 43,082
      trauma patient records were reviewed; 32,798 patients had complete RTS data
      available and 32,371 patients had complete data available for MGAP analyses. The
      correlation between scene RTS and ISS was poor (-.29), as was the correlation
      between MGAP and ISS (-.28). For the prediction of mortality, admission MGAP
      demonstrated the highest sensitivity and specificity for mortality (AUROC 0.96;
      95% CI, 0.95-0.96). CONCLUSIONS: While elements of the RTS remain the first
      criterion recommended to quantify the totality of physiological injury severity,
      the composite RTS score derived from this system correlates poorly with actual
      anatomical injury severity. The MGAP scoring system demonstrated higher
      sensitivity and specificity for mortality but was not superior to the RTS for
      predicting anatomical injury severity. In the future development of national and
      international field triage guidelines for trauma patients, the findings from this
      study may be considered in order to improve the accuracy of prehospital triage.
      The findings in this analysis complement a growing body of evidence that suggests
      that MGAP may be a superior and more easily calculable prehospital scoring system
      for the prediction of mortality in trauma patients.

PMID- 30118370
TI  - Medicare Utilization and Spending Among Nurses Compared with the General United
      States Population.
AB  - BACKGROUND: To better understand health habits in older nurses versus the general
      population, we sought to determine whether the demographics, health care
      utilization, and Medicare spending by the Nurses' Health Study (NHS) participants
      enrolled in Medicare and a matched sample of Medicare beneficiaries meaningfully
      differed. MATERIALS AND METHODS: Analytic cohorts included a random 20% sample of
      Medicare beneficiaries continuously enrolled in fee for service (FFS) Medicare
      that were propensity matched to the NHS participants continuously enrolled in FFS
      Medicare in a single year (2012). Matching was based upon preselected demographic
      factors and health status, using a nearest-neighbor matching algorithm to obtain
      a 1:1 match without replacement. Healthcare utilization and spending were
      compared between the two groups; we also stratified findings by number of chronic
      comorbidities. RESULTS: Similar rates of utilization of primary care and most
      outpatient services. However, NHS participants had slightly higher rates of
      cancer screening, specialist care, and inpatient surgery were observed. When
      stratified by comorbidity status, the largest differences in utilization and
      spending were found in women with no comorbidity. CONCLUSIONS: The modest
      differences in observed healthcare utilization and spending suggest that older
      healthcare professionals may access care in fairly similar ways to the general
      population, and that health status may be a more important determinant of
      utilization and spending than health profession in older age groups.

PMID- 30118371
TI  - Family Caregivers' Heavy and Overloaded Burden in Advanced Chronic Obstructive
      Pulmonary Disease.
AB  - BACKGROUND: Due to severe symptoms and poor prognosis in advanced cases, chronic
      obstructive pulmonary disease (COPD) is today seen as a palliative diagnosis. The
      everyday lives of patients as well as their relatives are restricted and affected
      by significant psychosocial problems. OBJECTIVE: To obtain detailed knowledge
      about people's experiences, for example, transitions in relationships,
      responsibility, and possible changes in communication, caused by the illness.
      DESIGN: This is a qualitative interview study using both focus group interviews
      and individual interviews. SETTING/SUBJECTS: In total, 35 family members with
      personal experience of living with a person with severe COPD were interviewed.
      MEASUREMENTS: The semistructured interviews were audio-recorded, transcribed
      verbatim, and analyzed with a qualitative content analysis. RESULTS: Three themes
      emerged: (1) A restricted everyday life. The family caregivers felt confined to
      their own home, they had to be constantly attentive, and their lives became
      increasingly restricted. (2) A changed relationship. There was a shift in
      responsibility and their mutual communication. The family caregivers' own needs
      were neglected and the relationship was affected. (3) Joy through adaption.
      Still, caregivers strived for normality and, through gradual adaption, they could
      still experience joy. CONCLUSIONS: Being a family caregiver is a burdensome and
      complex situation. Besides providing practical help, the family caregiver needs
      to support the ill person. Roles and communication patterns are changed.
      Healthcare staff must identify the needs of the family caregivers. A family
      caregiver who feels acknowledged and confident can support their severely ill
      family member.

PMID- 30118372
TI  - Prognostic Value of BEFAST vs. FAST to Identify Stroke in a Prehospital Setting.
AB  - BACKGROUND: Use of prehospital stroke scales may enhance stroke detection and
      improve treatment rates and delays. Current scales, however, may lack detection
      accuracy. As such, we examined whether adding coordination (Balance) and diplopia
      (Eyes) assessments increase the accuracy of the Face-Arms-Speech-Time (FAST)
      scale in a multisite prospective study of emergency response activations for
      presumed stroke. METHODS: This was a prospective study of emergency response
      activations for presumed stroke in Santa Clara County, California. Emergency
      medical responders were trained in the Balance-Eyes-Face-Arms-Speech-Time
      (BEFAST) scale and administered the scale on scene to all patients who were
      within 6 hours of onset of neurological symptoms. Each patient's final diagnosis
      (stroke vs. no stroke) was based on review of hospital records. We compared the
      performance of the BEFAST and FAST scales for stroke detection. RESULTS: Three
      hundred fifty-nine patients were included in our analysis. Compared to nonstroke
      patients (n = 200), stroke patients (n = 159) more often scored positive on each
      of the five elements of the BEFAST scale (p < 0.05 for each). In multivariable
      analysis, only facial droop and arm weakness were independent predictors of
      stroke (p < 0.05). BEFAST and FAST scale accuracy for stroke identification was
      comparable (area under the curve [AUC] = 0.70 vs. AUC = 0.69, p = 0.36). Optimal
      cutoff for stroke detection was >=1 for both scales. At this threshold, the
      positive predictive value (PPV) was 0.49 for the BEFAST and 0.53 for the FAST
      scale, and the negative predictive value (NPV) was 0.93 for BEFAST and 0.86 for
      FAST. CONCLUSION: Adding coordination and diplopia assessments to face, arm, and
      speech assessment does not improve stroke detection in the prehospital setting.

PMID- 30118373
TI  - "From a Family Home to Hell": Experiences and Consequences of Intimate Partner
      Violence Among Married Jordanian Women.
AB  - This study aimed to understand the experience of intimate partner violence (IPV)
      and related consequences among married Jordanian women. A qualitative exploratory
      design using semi-structured interviews (n = 10) was employed. Analysis of the
      qualitative data revealed two main themes. The first theme focused on the
      transition: "From a family home to Hell". The second theme was described as the
      path from wellness to illness, including an analysis of the various consequences
      of IPV. A continuous educational program for the victims themselves and
      healthcare professionals along with a serious partnership with legal and
      political institutions in Jordan is urgently needed.

PMID- 30118374
TI  - Cystic fibrosis respiratory microbiota: unraveling complexity to inform clinical
      practice.
AB  - INTRODUCTION: Cystic fibrosis (CF) lung disease is characterized by chronic
      cycles of pulmonary infection, inflammation, and mucus obstruction, beginning
      early in life, and eventually leading to progressive lung damage and early
      mortality. During the past ~15 years, culture-independent analyses of CF
      respiratory samples have identified diverse bacterial communities in CF airways,
      and relationships between respiratory microbiota and clinical outcomes. Areas
      covered: This paper reviews recent advances in our understanding of the
      relationships between respiratory microbiota and CF lung disease. The paper
      focuses on measures of airway bacterial community diversity and estimates of the
      relative abundance of anaerobic species. Finally, this paper will review the
      opportunities for advancing patient care suggested by these studies and highlight
      some of the ongoing challenges and unmet needs in translating this knowledge into
      clinical practice. Expert commentary: Culture-independent analyses of respiratory
      microbiota have suggested new strategies for advancing CF care, but have also
      highlighted challenges in understanding the complexity of CF respiratory
      infections. Development of more sophisticated models and analytic approaches to
      better account for this complexity are needed to elucidate mechanistic links
      between CF respiratory microbiota and clinical outcomes, and to ultimately
      translate this knowledge into better patient care.

PMID- 30118375
TI  - Regulation of protective autophagy in anoikis-resistant glioma stem cells by
      SDCBP/MDA-9/Syntenin.
AB  - Glioblastoma multiforme (GBM) is a frequent and aggressive glial tumor,
      containing a small population of therapy-resistant cells, glioma stem cells
      (GSCs). Current dogma suggests that tumors regrow from GSCs, and these cells
      contribute to therapy resistance, poor prognosis, and recurrence; highlighting
      the importance of GSCs in glioma pathophysiology and therapeutic targeting.
      Macroautophagy/autophagy-based cellular homeostasis can be changed from pro
      survival to pro-cell death by modulating SDCBP/MDA-9/Syntenin (syndecan binding
      protein)-mediated signaling. In nonadherent conditions, GSCs display protective
      autophagy and anoikis-resistance, which correlates with expression of SDCBP/MDA
      9/Syntenin. Conversely, SDCBP/MDA-9/Syntenin silencing induces autophagic death
      in GSCs, indicating that SDCBP/MDA-9/Syntenin regulates protective autophagy in
      GSCs under anoikis conditions. This process is mediated through phosphorylation
      of the anti-apoptotic protein BCL2 accompanied with suppression of high levels of
      autophagic proteins (ATG5, LAMP1, LC3B) through EGFR signaling. SDCBP/MDA
      9/Syntenin-mediated regulation of BCL2 and EGFR phosphorylation is achieved
      through PTK2/FAK and PRKC/PKC signaling. When SDCBP/MDA-9/Syntenin is absent,
      this protective mechanism is deregulated, leading to highly elevated and
      sustained levels of autophagy and consequently decreased cell survival. Our
      recent paper reveals a novel functional link between SDCBP/MDA-9/Syntenin
      expression and protective autophagy in GSCs. These new insights into SDCBP/MDA
      9/Syntenin-mediated regulation and maintenance of GSCs present leads for
      developing innovative combinatorial cancer therapies.

PMID- 30118376
TI  - Utilizing Pediatric Scoring Systems to Predict Disposition During Interfacility
      Transport.
AB  - OBJECTIVE: Determining care disposition for pediatric patients during
      interfacility transport is often challenging. Severity of illness scoring can
      assist with this process. The purpose of this retrospective study was to compare
      currently utilized scoring systems and their ability to reliably match pediatric
      transport patients' severity of illness with the level of care necessary.
      METHODS: The retrospective transport registry review for our region included 209
      patients <18 years, transported between 2015 and 2016 and admitted to tertiary
      care. The Pediatric RISk of Mortality III (PRISM III); Canadian Pediatric Triage
      and Acuity Scale (PedCTAS); Transport Pediatric Early Warning Scores (TPEWS); and
      Transport Risk Assessment in Pediatrics (TRAP) scores were calculated.
      Descriptive statistics and binomial logistic regression were utilized to compare
      the scoring tools. Interrater reliability was calculated using kappa statistics.
      All analyses were computed using IBM SPSS Statistics for Windows, version 24.
      RESULTS: Patients were more likely to be admitted to pediatric intensive care
      unit (PICU) with PedCTAS = 1 (odds ratio [OR] = 37.2; 95% confidence interval
      [CI], 12.4, 111.4; p < 0.0001), TPEWS = 3 in one category or total score >=6 (OR
      = 42.2; 95% CI, 17.0, 104.9; p < 0.0001), and TRAP >=4 (OR = 7.2; 95% CI, 3.8,
      13.5; p < 0.0001). PRISM scores were not predictive for PICU admissions.
      CONCLUSION: Elevated PedCTAS, TPEWS, and TRAP scores are strongly associated with
      PICU admission within the interfacility transport setting.

PMID- 30118377
TI  - Severe community-acquired pneumonia: current management and future therapeutic
      alternatives.
AB  - INTRODUCTION: Despite advances in modern medicine, severe community-acquired
      pneumonia (CAP) continues to be a potentially deadly disease. Mortality rate
      reaches up to the 50% in patients requiring admission to the Intensive Care Unit
      (ICU) when developing septic shock. Areas covered: We aim to describe the optimal
      management of severe CAP, including antibiotic therapy, future antimicrobial
      options, and non-antibiotic (so-called adjunctive) therapies. A literature search
      was performed to identify all clinical trials, observational studies, meta
      analysis, and reviews about this topic from PubMed. Expert commentary: Antibiotic
      therapy, the cornerstone of the management of CAP, must be started prompt because
      the delay in the administration of antimicrobials is associated with mortality.
      Diverse observational studies have reported a lower adjusted mortality in
      patients with severe CAP treated with combined antibiotic therapy, especially
      those in septic shock or with pneumococcal bacteremia. We summarize the available
      information about new antibiotics in the pipeline for severe CAP. Finally, we
      review the available evidence about the role of corticosteroids, immunoglobulins,
      and statins as adjunctive for CAP.

PMID- 30118378
TI  - Microbial biotransformation - an important tool for the study of drug metabolism.
AB  - Metabolite identification is an integral part of both preclinical and clinical
      drug discovery and development. Synthesis of drug metabolites is often required
      to support definitive identification, preclinical safety studies and clinical
      trials. Here we describe the use of microbial biotransformation as a tool to
      produce drug metabolites, complementing traditional chemical synthesis and other
      biosynthetic methods such as hepatocytes, liver microsomes and recombinant human
      drug metabolizing enzymes. A workflow is discussed whereby microbial strains are
      initially screened for their ability to form the putative metabolites of
      interest, followed by a scale-up to afford quantities sufficient to perform
      definitive identification and further studies. Examples of the microbial
      synthesis of several difficult-to-synthesize hydroxylated metabolites and three
      difficult-to-synthesize glucuronidated metabolites are described, and the use of
      microbial biotransformation in drug discovery and development is discussed.

PMID- 30118379
TI  - Conventional culture methods with commercially available media unveil the
      presence of novel culturable bacteria.
AB  - Recent metagenomic analysis has revealed that our gut microbiota plays an
      important role in not only the maintenance of our health but also various
      diseases such as obesity, diabetes, inflammatory bowel disease, and allergy.
      However, most intestinal bacteria are considered 'unculturable' bacteria, and
      their functions remain unknown. Although culture-independent genomic approaches
      have enabled us to gain insight into their potential roles, culture-based
      approaches are still required to understand their characteristic features and
      phenotypes. To date, various culturing methods have been attempted to obtain
      these 'unculturable' bacteria, but most such methods require advanced techniques.
      Here, we have tried to isolate possible unculturable bacteria from a healthy
      Japanese individual by using commercially available media. A 16S rRNA (ribosomal
      RNA) gene metagenomic analysis revealed that each culture medium showed bacterial
      growth depending on its selective features and a possibility of the presence of
      novel bacterial species. Whole genome sequencing of these candidate strains
      suggested the isolation of 8 novel bacterial species classified in the
      Actinobacteria and Firmicutes phyla. Our approach indicates that a number of
      intestinal bacteria hitherto considered unculturable are potentially culturable
      and can be cultured on commercially available media. We have obtained novel gut
      bacteria from a healthy Japanese individual using a combination of comprehensive
      genomics and conventional culturing methods. We would expect that the discovery
      of such novel bacteria could illuminate pivotal roles for the gut microbiota in
      association with human health.

PMID- 30118380
TI  - Quality And Feasibility of Sonographic Measurement of the Optic Nerve Sheath
      Diameter to Estimate the Risk of Raised Intracranial Pressure After Traumatic
      Brain Injury in Prehospital Setting.
AB  - OBJECTIVE: In patients with traumatic brain injury (TBI), early detection and
      subsequent prompt treatment of elevated intracranial pressure (ICP) is a
      challenge in the prehospital setting, because physical examination is limited in
      comatose patients and invasive device placement is not possible. The aim of this
      study was to evaluate the quality and feasibility of optic nerve sheath diameter
      (ONSD) measurements obtained during the prehospital management of patients with
      TBI. METHODS: This study was a prospective, observational study of 23 patients
      with moderate and severe TBI during prehospital medical care. The primary
      endpoint was the quality of ONSD measurements expressed as the percentage of ONSD
      validated by the experts. Secondary endpoints included the feasibility of ONSD
      measurements as the percentage of ONSD performed and assessment by operators of
      ease and duration to perform. RESULTS: Ultrasound ONSD was performed in 19 (82%)
      patients and 80% of ONSD measurements were validated by the experts. The ONSD
      measurements were possible in 15 (79%) cases. The physicians have assessed the
      ease of use at 8 (interquartile range [IQR] = 2.5-8) on 10 for and the median
      time to obtain ONSD measurement was 4 min (IQR = 3-5). ONSD measurement was
      performed in 12 (63%) cases during the transport and in 7 (37%) cases on scene,
      with 58% (n = 7) and 71% (n = 5) validated ONSD, respectively. The success rate
      in the helicopter was 43% compared to 80% in the ambulance. CONCLUSION: This
      study shows that it is feasible to obtain high-quality ONSD measurements in the
      management of patients with TBI in a prehospital setting. A randomized study
      evaluating the usefulness of ONSD to guide management of TBI in the prehospital
      phase may be of great interest.

PMID- 30118381
TI  - HPV vaccine confidence and cases of mass psychogenic illness following
      immunization in Carmen de Bolivar, Colombia.
AB  - We report the case of multiple adverse reactions following HPV vaccination in
      Colombian adolescents in Carmen de Bolivar. In August 2012, the country
      introduced a school-based HPV immunization programme which successfully reached
      over 90% of the target population in the first year. In 2014, between May 29th
      and June 2nd,15 adolescent girls in one school presented adverse reactions after
      vaccination and were admitted to the local hospital. Soon, videos of girls
      fainting, twitching, and arriving unconscious at emergency rooms started to
      appear in national news media as well as on social media platforms such as
      YouTube. The viral spread of these videos and disturbing images were followed by
      the viral spread of symptoms, with over 600 cases reported across Colombia.
      Thorough epidemiological investigation by Colombian health authorities found no
      organic association between the teenagers' symptoms and the HPV vaccine,
      concluding this was a case of mass psychogenic reaction to vaccination.
      Scientific evidence did not appease the anxious public whose confidence in HPV
      immunization dropped dramatically. By 2016, HPV vaccine uptake among eligible
      girls declined to 14% for the first dose and 5% for the complete course, down
      from 98% and 88%, respectively, in 2012. We document this case and discuss the
      role of news and social media, particularly YouTube, as a driver of contagious
      psychogenic reactions. We also discuss the role of health authorities and
      government, and the importance of acting rapidly and appropriately to contain the
      spread of such symptoms and maintain public confidence in vaccines.

PMID- 30118382
TI  - Patient and family expectations of beta-cell replacement therapies in type 1
      diabetes.
AB  - BACKGROUND: New methods of beta-cell replacement have been developed to maintain
      excellent glycemic control, improve quality of life, and even eliminate insulin
      injections in patients with type 1 diabetes mellitus (T1DM). Previously, we
      demonstrated that being insulin-free is the strongest motivation for accepting a
      newly developed therapy. Multiple allogeneic islet transplantations with
      immunosuppression using a human donor is the best option to be insulin-free, but
      the necessity for immunosuppression and donor shortage are major issues. However,
      these issues have been improved with scientific progress. The aim of this study
      was to investigate the opinions of patients and their families about the current
      progress. METHODS: We conducted a questionnaire survey of T1DM patients (n = 47)
      and their family members (n = 49) about newly developed therapies: single and
      multiple allogeneic islet transplantation, single and multiple encapsulated
      allogeneic islet transplantation, single and multiple xenogeneic islet
      transplantation, and induced pluripotent stem cell therapy. RESULTS: More than
      90% of respondents wished to be insulin-free and have stable glycemic control.
      More than 90% of respondents accepted at least one of the new therapies. The
      current standard treatment multiple allogeneic islet transplantation was not well
      accepted or favored. CONCLUSIONS: The next generation of treatments, including
      xenotransplantation and induced pluripotent stem cell therapy, were more
      acceptable and favorable. Even though the majority of patients wish to become
      insulin-free, it is not sufficiently strong motivation for accepting newly
      developed treatments.

PMID- 30118383
TI  - Management of Adnexal Torsion: A 13-Year Experience in Single Tertiary Center.
AB  - PURPOSE: Adnexal torsion constitutes 2.7% of gynecological emergencies, it is
      more frequently seen in reproductive age. Delay in diagnosis and treatment may
      lead to loss of the ovary. In this study, we aimed to assess patients who had
      adnexal torsion and compare laparoscopy with laparotomy in the treatment of these
      patients and point the most appropriate surgery according to age groups of the
      patients and comparison of patient characteristics and management between adnexal
      torsion in postmenopausal and premenopausal patients. MATERIALS AND METHODS: This
      study was carried out in Necmettin Erbakan University, Meram Medicine Faculty,
      Department of Obstetrics and Gynecology. The study retrospectively analyzed 380
      patients presented to our clinic with abdominal pain between January 2005 and
      December 2017 and had surgery for adnexal torsion. RESULTS: The study included
      380 patients who had surgery for adnexal torsion. A total of 220 patients had
      laparoscopy and 160 patients had laparotomy. Laparoscopy group consisted of young
      patients with low parity, whereas laparotomy group consisted of 160 patients of
      which 92 (57.5%) were in menopause. Teratomas were the most common pathological
      finding followed by follicular cysts. Fourteen ovarian malignancies and 11
      borderline tumors had been reported. Eleven ovarian malignancies had been
      reported in postmenopausal patients and three in premenopausal patients.
      CONCLUSION: Laparoscopic surgery is preferred for young patients who want to
      preserve their fertility, but postmenopausal ovarian masses presenting with
      torsion should be analyzed with frozen section whenever possible, if not possible
      or not conclusive, staging surgery is more appropriate especially if there is
      suspicion of malignancy.

PMID- 30118384
TI  - Profile of polycyclic aromatic hydrocarbons in digested sewage sludge.
AB  - One of the methods of sludge disposal in cities is its use as an amendment in
      adjoining agricultural soil. Contaminants in sludge can, however, nullify the
      benefits. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent
      organic pollutants, if present, can pose health risks by virtue of their
      carcinogenic potential and persistence in soil. The present study deals with
      profile analysis of PAHs in digested sewage sludge of a megacity, Delhi. Mean
      concentration of the sum of 16 PAHs in the sludge from 5 sewage treatment plants
      (STPs) was 20.67 +/- 4.14 mg/kg, dry weight (dw). Carcinogenic PAHs represented
      ~47% of the total PAHs. Benzo[g,h,i]perylene recorded the highest mean
      concentration followed by dibenzo[a,h]anthracene. Low molecular weight PAHs and
      high molecular weight PAHs contributed 19% and 81% to total PAHs content
      respectively. Principal component analysis identified the major sources of PAHs
      in sludge as coal and natural gas combustion. Wood combustion, oil and oil
      derivatives are the other identified sources. The observed PAH levels in sludge
      from selected STPs of Delhi were found to violate the limit values proposed by
      the European Union and the US legislation for application in agriculture.

PMID- 30118385
TI  - Links between environment, diet, and the hunter-gatherer microbiome.
AB  - The study of traditional populations provides a view of human-associated microbes
      unperturbed by industrialization, as well as a window into the microbiota that co
      evolved with humans. Here we discuss our recent work characterizing the
      microbiota from the Hadza hunter-gatherers of Tanzania. We found seasonal shifts
      in bacterial taxa, diversity, and carbohydrate utilization by the microbiota.
      When compared to the microbiota composition from other populations around the
      world, the Hadza microbiota shares bacterial families with other traditional
      societies that are rare or absent from microbiotas of industrialized nations. We
      present additional observations from the Hadza microbiota and their lifestyle and
      environment, including microbes detected on hands, water, and animal sources, how
      the microbiota varies with sex and age, and the short-term effects of introducing
      agricultural products into the diet. In the context of our previously published
      findings and of these additional observations, we discuss a path forward for
      future work.

PMID- 30118386
TI  - Safety and immunogenicity of an upper-range release titer measles-mumps-rubella
      vaccine in children vaccinated at 12 to 15 months of age: a phase III, randomized
      study.
AB  - The titer of live attenuated viral vaccines, such as MMR vaccines, varies between
      batches and over the shelf-life of a batch, with the highest titer expected at
      batch release. As higher titers may theoretically lead to increased
      reactogenicity, we compared the safety profile of an upper-range release titer
      MMR-RIT lot with commercial MMR II lots in a phase III, randomized, controlled
      study (NCT02184572). We vaccinated 1736 children with MMR-RIT (N = 1164) or MMR
      II (N = 572), both administered as first doses with varicella, hepatitis A, and
      pneumococcal conjugate vaccines at 12-15 months of age. The incidence of fever 5
      12 days post-vaccination was comparable following MMR-RIT and MMR II vaccination:
      4.2% vs 3.1% (difference: 1.1%) for fever > 39.0 degrees C and 18.2% vs 17.1%
      (difference: 1.1%) for fever >= 38.0 degrees C, which met the primary objective.
      Two cases of febrile convulsions (one considered vaccination-related) were
      reported within 43 days post-MMR-RIT. During Days 0-42, rashes were reported for
      24.4% (MMR-RIT) and 27.4% (MMR II) of children; measles/rubella-like rashes for
      5.8% and 4.7%, respectively. Measles-like illnesses were reported for 1.5% (MMR
      RIT) and 0.9% (MMR II) of children 5-12 days post-vaccination. One serious
      adverse event, immune thrombocytopenic purpura following MMR II vaccination, was
      considered vaccination-related. Immune responses were similar in both groups. In
      summary, the safety profile of an upper-range release titer MMR-RIT lot was in
      line with that of commercial MMR II lots, with similar rates of fever and other
      MMR-specific symptoms and low rates of measles-like illnesses reported with both
      vaccines.

PMID- 30118387
TI  - Low temperature selective catalytic reduction of nitric oxide with urea over
      activated carbon supported metal oxide catalysts.
AB  - Selective catalytic reduction of nitrogen oxides (SCR) with loaded urea is a
      method for removing NO under oxygen-rich and low-temperature conditions, which
      can solve the inhibitory effect of oxygen on the catalyst and the slip of
      ammonia. In present study, a series of activated carbon (wo-AC, co-AC, cs-AC and
      nu-AC) supported metal (Mn, Fe, Co, Cu and Zn) oxide catalysts with loading urea
      were prepared by ultrasonic assisted impregnation. The catalysts were used for NO
      removal at 50-120 degrees C and characterized by XRD, SEM, GFAAS, EDS, XPS, BET
      and FTIR techniques. The effects of activated carbon type, loaded active element,
      metal oxides loading, temperature fluctuation on catalytic activity and the
      catalytic stability were also studied in this paper. The results indicated that
      nutshell-based activated carbon was more suitable as a carrier than other
      activated carbons, and urea-10Mn/nu-AC catalyst yielded a higher NO conversion
      than other catalysts. Besides, for used activated carbons, the larger specific
      surface area, more micropores distribution and the larger number of hydroxyl
      group and cyano terminal group are beneficial to the catalytic process. Moreover,
      the downward trend of NO conversion with increasing temperature suggested the
      adsorption of reactant gases played a crucial role in the catalytic process of
      urea-SCR.

PMID- 30118388
TI  - The Structural and Functional Signature of Action Control.
AB  - Individuals differ in their ability to initiate self- and emotional-control
      mechanisms. These differences have been explicitly described in Kuhl's action
      control theory. Although interindividual differences in action control make a
      major contribution to our everyday life, their neural foundation remains unknown.
      Here, we measured action control in a sample of 264 healthy adults and related
      interindividual differences in action control to variations in brain structure
      and resting-state connectivity. Our results demonstrate a significant negative
      correlation between decision-related action orientation (AOD) and amygdala
      volume. Further, we showed that the functional resting-state connectivity between
      the amygdala and the dorsal anterior cingulate cortex was significantly
      associated with AOD. Specifically, stronger functional connectivity was
      associated with higher AOD scores. These findings are the first to show that
      interindividual differences in action control, namely AOD, are based on the
      anatomical architecture and functional network of the amygdala.

PMID- 30118389
TI  - The role of trehalose in the global spread of epidemic Clostridium difficile.
AB  - In a recent study, we reported on two distantly related, epidemic lineages of
      Clostridium difficile that have acquired independent mechanisms to metabolize low
      concentrations of trehalose. Here we provide further comment and evidence that a
      third epidemic lineage common in Asia and Europe, ribotype 017, has evolved this
      ability.

PMID- 30118390
TI  - Robotic Surgery of the Liver and Biliary Tract.
AB  - BACKGROUND: The laparoscopic methods for major abdominal surgery are gaining
      increasing acceptance worldwide. Despite its relatively recent introduction in
      clinical practice, robotics has been accepted as an effective option to perform
      high-demanding procedures such as those required in hepatobiliary surgery. Some
      potential advantages over conventional laparoscopy have been suggested, but its
      actual role in clinical practice is still to be defined. METHODS: The objective
      of this work is to critically review the available evidence on the application of
      robotic surgery to the liver and biliary tract. PubMed, Embase, and the Cochrane
      Library electronic databases were systematically searched for studies reporting
      on robotic hepatobiliary surgery with or without comparison with open surgery or
      conventional laparoscopy. RESULTS: This review provides a comprehensive snapshot
      of the current application of the robot to the surgery of the liver and biliary
      tract. The overall available data show the noninferiority of the robotic system
      to conventional open and laparoscopic surgery. A number of studies suggest some
      potential advantages in performing high-demanding procedures in a minimally
      invasive fashion. CONCLUSIONS: The robot can be used to perform various types of
      liver surgeries quite safely and competently, although the lack of randomized
      control trials, comparing it with open and laparoscopic surgery, precludes the
      possibility to reach definitive conclusions.

PMID- 30118391
TI  - The biomechanical effect of warm-up stretching strategies on landing mechanics in
      female volleyball athletes.
AB  - Female volleyball athletes incorporate dynamic and static stretching into a warm
      up, with evidence generally supporting dynamic stretching to improve performance.
      However, the effects of these stretching practices on injury risk during
      subsequent volleyball manoeuvres have yet to be fully elucidated in the warm-up
      literature. Three-dimensional kinematic data associated with non-contact, lower
      extremity injury were recorded on 12 female collegiate club volleyball athletes
      during unilateral landing tasks on the dominant and non-dominant limb.
      Participants performed landings as part of a volleyball-simulated manoeuvre prior
      to and post-dynamic (DWU) and combined dynamic-static (CDS) warm-ups. A
      significant reduction in non-dominant hip adduction angle was found at 15 min
      post CDS warm-up (p = 0.016; d = 0.38), however, no other warm-up differences
      were detected. The non-dominant limb demonstrated greater knee abduction (p =
      0.006; d = 0.69) and internal rotation angle (p = 0.004; d = 0.88), suggesting
      that this limb demonstrates more risky landing patterns that are potentially due
      to altered trunk positioning upon landing. The results show that the majority of
      selected landing kinematics are unaffected by additional static stretching to a
      dynamic warm-up and that the non-dominant limb may be at a higher injury risk in
      female volleyball athletes.

PMID- 30118392
TI  - Osteochondral Lesions of the Knee: Differentiating the Most Common Entities at
      MRI.
AB  - Several pathologic conditions may manifest as an osteochondral lesion of the knee
      that consists of a localized abnormality involving subchondral marrow,
      subchondral bone, and articular cartilage. Although understanding of these
      conditions has evolved substantially with the use of high-spatial-resolution MRI
      and histologic correlation, it is impeded by inconsistent terminology and
      ambiguous abbreviations. Common entities include acute traumatic osteochondral
      injuries, subchondral insufficiency fracture, so-called spontaneous osteonecrosis
      of the knee, avascular necrosis, osteochondritis dissecans, and localized
      osteochondral abnormalities in osteoarthritis. Patient demographics, the clinical
      presentation, and the role of trauma are critical for differential diagnosis. A
      localized osteochondral defect can be created acutely or can develop as an end
      result of several chronic conditions. MRI features that aid in diagnosis include
      the location and extent of bone marrow edema, the presence of a fracture line, a
      hypointense area immediately subjacent to the subchondral bone plate, and
      deformity of the subchondral bone plate. These findings are essential in
      diagnosis of acute traumatic injuries, subchondral insufficiency fracture, and
      its potentially irreversible form, spontaneous osteonecrosis of the knee. If the
      lesion consists of a subchondral region demarcated from the surrounding bone, the
      demarcation should be examined for completeness and the presence of a "double
      line sign" that is seen in avascular necrosis or findings of instability, which
      are important for proper evaluation of osteochondritis dissecans. Subchondral
      bone plate collapse, demonstrated by the presence of a depression or a fluid
      filled cleft, can be seen in advanced stages of both avascular necrosis and
      subchondral insufficiency fracture, indicating irreversibility. Once the
      diagnosis is established, it is important to report pertinent MRI findings that
      may guide treatment of each condition. (c)RSNA, 2018 An earlier incorrect version
      of this article appeared online. This article was corrected on August 23, 2018.

PMID- 30118393
TI  - PET/CT in the Diagnosis and Workup of Sarcoidosis: Focus on Atypical
      Manifestations.
AB  - Sarcoidosis is a multisystem disease characterized by the formation of
      noncaseating granulomas. Lung and intrathoracic lymph nodes are classic sites of
      involvement; however, sarcoidosis can affect any site in the body. The clinical
      course is extremely variable, and the imaging features are diverse and dependent
      on the affected site, degree of inflammation, and treatment the patient receives.
      Atypical manifestations and imaging findings can make diagnosis and/or management
      challenging. In addition, assessment of treatment response can be difficult in
      the setting of chronic disease. Fluorine 18 fluorodeoxyglucose (FDG) PET/CT is
      sensitive for assessment of the inflammatory activity of sarcoidosis in any
      organ. Although FDG PET/CT is not included in the standard workup for
      sarcoidosis, there has been growing evidence that supports the value of this
      examination in guiding diagnosis and management. FDG PET/CT may be especially
      useful for assessing reversible granuloma, treatment response, disease extent,
      occult disease, and cardiac or osseous sarcoidosis, and determining the most
      suitable biopsy site. Capability to image the entire body during a single
      examination is advantageous in cases of systemic disease such as sarcoidosis. The
      authors review the use of FDG PET/CT, providing up-to-date evidence and
      describing various cases of sarcoidosis in which FDG PET/CT has an important role
      in diagnosis and/or management. They also discuss the usefulness of FDG PET/CT in
      cases of selective manifestations of sarcoidosis. (c)RSNA, 2018.

PMID- 30118394
TI  - Differences in impact characteristics, joint kinetics and measurement reliability
      between forehand and backhand forward badminton lunges.
AB  - This study identified the effect of badminton lunging directions on impact
      characteristics, joint kinetics and measurement reliability. A total of 14
      badminton players performed 20 lunges in both forehand and backhand sides. Ground
      reaction force (GRF) and three-dimensional joint moment variables were determined
      for further analyses. Paired t-tests and Wilcoxon signed-rank tests were
      performed to determine any differences between the two lunge directions and intra
      class correlation (ICC) and sequential averaging analysis (SAA) were used to
      estimate the minimum number of trials. Compared to the forehand side,
      participants experienced significantly larger total GRF impulse (+ 3.8%, p =
      0.021) and transverse moment (hip + 63.5%, p < 0.001; knee + 80.7%, p = 0.011),
      but smaller hip (-7.7%), knee (-18.7%) and ankle frontal moments (-58.0%, p <
      0.05) in backhand lunges. The minimum number of trials was similar for both lunge
      directions, as the averaged absolute differences was less than one in both ICC
      and SAA. Furthermore, smaller minimal number of trials was determined by the ICC
      (7.9-8.0), compared with the SAA approach (9.5-10.3). Lunge direction would
      influence GRF and joint loading, but not on the measurement reliability. These
      results give important insights to establish performance or equipment evaluation
      protocols during badminton lunges.

PMID- 30118396
TI  - Viral Epitope Escape in Acute HIV-1 Infection.

PMID- 30118395
TI  - Occurrence of deoxynivalenol in an elderly cohort in the UK: a biomonitoring
      approach.
AB  - Deoxynivalenol (DON) is a Fusarium toxin, to which humans are frequently exposed
      via diet. Although the elderly are speculated to be sensitive to the toxic
      effects of DON as a result of age-related conditions, disease and altered DON
      metabolism, there is lack of available data on DON biomarkers in this age group.
      This study characterised urinary DON concentrations and its metabolites in
      elderly aged >=65years (n = 20) residing in Hull, UK. Morning urinary specimens
      were collected over two consecutive days together with food records to assess
      dietary intake over a 24h-period prior to each urinary collection. Free DON (un
      metabolised), total DON (sum of free DON and DON-glucuronides or DON-GlcA) and de
      epoxy deoxynivalenol (DOM-1) were analysed using a validated LC-MS/MS
      methodology. Total DON above the limit of quantification 0.25 ng/mL was detected
      in the urine from 90% of elderly men and women on both days. Mean total DON
      concentrations on day 1 were not different from those on day 2 (elderly men, day
      1: 22.2 +/- 26.3 ng/mg creatinine (creat), day 2: 28.0 +/- 34.4 ng/mg creat, p =
      0.95; elderly women, day 1: 22.4 +/- 14.6 ng/mg creat, day 2: 29.1 +/- 22.8 ng/mg
      creat, p = 0.58). Free DON and DON-GlcA were detected in 60-70% and 90% of total
      urine samples, respectively. DOM-1 was absent from all samples; the LoQ for DOM-1
      was 0.50 ng/mL. Estimated dietary intake of DON suggested that 10% of the elderly
      exceeded the maximum provisional tolerable daily intake for DON. In this single
      site, UK-based cohort, elderly were frequently exposed to DON, although mean
      total DON concentrations were reported at moderate levels. Future larger studies
      are required to investigate DON exposure in elderly from different regions of the
      UK, but also from different counties worldwide.

PMID- 30118397
TI  - Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and
      Pituitary in Pediatric and Young Adult Patients With Brain Tumors.
AB  - PURPOSE: There are sparse data defining the dose response of radiation therapy
      (RT) to the hypothalamus and pituitary in pediatric and young adult patients with
      brain tumors. We examined the correlation between RT dose to these structures and
      development of endocrine dysfunction in this population. MATERIALS AND METHODS:
      Dosimetric and clinical data were collected from children and young adults (< 26
      years of age) with brain tumors treated with proton RT on three prospective
      studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone,
      adrenocorticotropic hormone, and gonadotropins were determined clinically and
      serologically. Incidence of deficiency was estimated using the Kaplan-Meier
      method. Multivariate models were constructed accounting for radiation dose and
      age. RESULTS: Of 222 patients in the study, 189 were evaluable by actuarial
      analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with
      31 patients (14%) excluded from actuarial analysis for having baseline hormone
      deficiency and two patients (0.9%) because of lack of follow-up. One hundred
      thirty patients (68.8%) with medulloblastoma were treated with craniospinal
      irradiation (CSI) and boost; most of the remaining patients (n = 56) received
      involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade
      glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency,
      growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin
      deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start
      of RT, time interval since treatment, and median dose to the combined
      hypothalamus and pituitary were correlated with increased incidence of
      deficiency. CONCLUSION: Median hypothalamic and pituitary radiation dose, younger
      age, and longer follow-up time were associated with increased rates of
      endocrinopathy in children and young adults treated with radiotherapy for brain
      tumors.

PMID- 30118398
TI  - Vaccination coverage and associated factors among children aged 12 - 23 months in
      Northwest Ethiopia.
AB  - BACKGROUND: Full vaccination coverage has been identified as the foundation for
      the prevention of morbidity and mortality from the childhood illnesses. However,
      a significant number of children do not get recommended vaccinations. The problem
      is much worse in low-income countries with varied figures and evidence gap.
      Therefore, this study was conducted to assess vaccination coverage and its
      predicting factors in one of the low-income country Ethiopia, particularly in
      northwest Ethiopia. METHODS: A community-based cross-sectional study was
      conducted in Northwest Ethiopia in 2016 on 846 children aged 12 to 23 completed
      months. Cluster sampling method was used. Mothers or caretakers were interviewed.
      SPSS version 20 was used for analysis. RESULTS: In Northwest Ethiopia, full
      vaccination coverage for the children aged 12-23 months was 58.4%, while 17% and
      24.6% were partially vaccinated and not vaccinated at all respectively. Child
      full vaccination status has a positive association with urban residence, having
      antenatal care visit, institutional delivery for the study child, vaccination
      site at health institutions, mothers who knows vaccination schedule of a
      catchment area, and mothers taking a child for vaccination even if the child is
      sick. However, mothers who ever-married and their travel time to the nearest
      vaccination site <= 30 minutes were negatively associated with child full
      vaccination status. CONCLUSION: Vaccination coverage in Northwest Ethiopia, East
      Gojam, is better than the national coverage. Yet, it is far below the plan.
      Encouraging antenatal care utilization, delivery at health institutions, and
      providing adequate information on child vaccination (including when to start,
      return and finish) for mothers would increase full-vaccination coverage.

PMID- 30118399
TI  - Acceptability of Injectable and On-Demand Pre-Exposure Prophylaxis Among an
      Online Sample of Young Men Who Have Sex with Men in California.
AB  - PURPOSE: Pre-exposure prophylaxis (PrEP) is an effective strategy to prevent HIV.
      However, low uptake of daily oral PrEP since Food and Drug Administration
      approval and low medication adherence among users have stimulated the
      investigation of other modalities for delivery, such as injectable PrEP and on
      demand PrEP. The objective of this study was to determine the demographic and
      behavioral predictors of willingness to try alternative PrEP delivery mechanisms
      among young men who have sex with men (YMSM) who stated that they were unwilling
      to try daily oral PrEP. METHODS: YMSM in California were recruited through
      geosocial networking applications; we analyzed a subsample who stated that they
      were either ambivalent about trying or unwilling to try daily oral PrEP (n =
      265). We used chi-square and Fisher's exact tests to determine characteristics
      associated with willingness to try injectable PrEP, willingness to try on-demand
      PrEP, and willingness to try either alternative form. RESULTS: For individuals
      who stated that they would not be willing to try daily oral PrEP, ~85% were
      willing to try on-demand and/or injectable PrEP. Individuals who reported some
      college or more reported greater willingness to try injectable PrEP (adjusted
      odds ratio [aOR]: 2.92; 95% confidence interval [CI]: 1.32-6.46), on-demand PrEP
      (aOR: 2.28; 95% CI: 1.06-4.90), or either method (aOR: 5.54; 95% CI: 1.78-17.22).
      CONCLUSION: Future research should determine how to enhance uptake of emerging
      forms of PrEP among the individuals most at risk for HIV.

PMID- 30118400
TI  - An investigation of presence of 2- and 3-monochloropropanediol fatty acid esters
      in Canadian human milk samples.
AB  - Occurrence of 2- and 3-monochloropropanediol fatty acid esters (MCPDEs) in 199
      human milk samples collected from Canadian women was examined in this study.
      MCPDEs were determined via indirect analytical approach by using acidic
      hydrolysis/transesterification and derivatization with cyclohexanone using a
      fluorinated sulfonic acid resin as a catalyst followed by GC-MS analysis.
      Analyses were done by a stable isotope dilution assay (SIDA) using 3
      monochloropropanediol-d5 dipalmitate and 2-monochloropropanediol-d5 distearate as
      internal standards. In all samples 2-MCPD esters were not detected, at LOD = 1
      ng/g for 2-MCPD equivalent. 3-MCPD esters were not detected, at LOD = 2 ng/g for
      3-MCPD equivalent, in 193 samples. Six samples had the apparent concentration of
      3-MCPD equivalent in the range of 2.0-5.1 ng/g, which was likely caused by
      accidental contamination during processing of samples. For selected samples,
      these findings were confirmed by direct analysis via LC-MS/MS analysis based on
      SIDA for 3-MCPD dipalmitate and 2-MCPD distearate. To our best knowledge, this is
      the first study to analyze human milk samples for 2-MCPD esters.

PMID- 30118401
TI  - Enhanced activity of superoxide dismutase is a common response to dietary and
      genetically induced increased cholesterol levels.
AB  - OBJECTIVES: Hypercholesterolaemia has been implicated in the pathogenesis of
      neurodegenerative diseases. In this work, we tested whether cholesterol-mediated
      neurodegeneration induced either by cholesterol-rich diet or genetic mutation may
      share a common mechanism involving increased oxidative stress and mitochondria
      oxidant status. Additionally, we analysed whether upon cholesterol-rich diet,
      different brain regions (prefrontal cortex, cortex, hippocampus, and cerebellum)
      show distinct vulnerability to an oxidative stress response. METHODS: Oxidative
      stress parameters were measured both in vivo (in the liver and in different brain
      regions) in cholesterol-fed mice and in vitro in genetically induced cholesterol
      accumulation in NPC1-null cells. RESULTS: Increased superoxide dismutase (SOD)
      activity was a common feature of cholesterol-mediated antioxidant response in
      both models. Moreover, upon high-cholesterol diet, all four brain regions
      analysed responded via somewhat different capacity of antioxidant defence,
      hippocampus showing the highest basal activity of SOD. Increased activity of SOD
      upon cholesterol accumulation in vitro involves mitochondrial SOD2. We found that
      SOD/SOD2 activities are modulated by cholesterol levels. DISCUSSION:
      Hypercholesterolaemia could potentiate brain dysfunction and neurodegenerative
      processes via oxidative stress, and activity of mitochondrial SOD2 may play a key
      role in this process. Our findings suggest that preventing/reducing mitochondrial
      oxidative stress may represent a common approach against neurodegenerative
      diseases.

PMID- 30118402
TI  - Travel Cost Savings and Practicality for Low-Vision Telerehabilitation.
AB  - INTRODUCTION: Veterans with low vision who live in rural communities have limited
      access to low-vision rehabilitation services, unless they are able to travel
      several miles to a specialty low-vision clinic. A low-vision optometry
      telerehabilitation evaluation is a thorough assessment of patient's functional
      vision. Following each low-vision optometry telerehabilitation evaluation is a
      low-vision telerehabilitation initial assessment with a blind rehabilitation
      therapist. Our objective was to estimate the acceptance and practicality of low
      vision telerehabilitation and investigate the travel cost and time savings.
      METHODS: Utilizing Google MapsTM, round-trip travel mileage and travel time can
      be estimated between the veteran's home and the Buffalo Veterans Affairs (VA) and
      compared with the round-trip mileage and travel time between the veteran's home
      and local community-based outpatient center (CBOC) or local VA for low-vision
      telerehabilitation services. The difference is the savings in travel miles and
      time. Cost saving can be calculated by multiplying difference in travel miles by
      cost per mile. RESULTS: Veterans who chose not to schedule face-to-face low
      vision rehabilitation at the Buffalo VA due to an average round-trip travel
      distance of 151 miles scheduled a low-vision telerehabilitation at a local CBOC
      or local VA with an average round-trip travel distance of 29 miles. Adding low
      vision telerehabilitation services from fiscal year (FY) 13 to FY 17 resulted in
      a 24% increase in low-vision patient care. The median saving of travel miles for
      rural veterans was 122 miles per veteran, and the median saving of travel time
      was 2.09 h per veteran. Overall, the median saving of the travel cost was $65.29
      per veteran. CONCLUSIONS: This study shows and supports low-vision
      telerehabilitation as an accepted, practical, time-saving, and cost-saving
      alternative option to traditional face-to-face consultations with a low-vision
      optometrist and blind rehabilitation therapist.

PMID- 30118403
TI  - Entero-neovesical fistula after radical cystectomy and orthotopic ileal
      neobladder: A report of two cases requiring surgical management.
AB  - INTRODUCTION: Entero-neovesical fistula is a rare complication after radical
      cystectomy and orthotopic ileal bladder substitution. Typical presenting symptoms
      are faecaluria, pneumaturia, recurrent urinary tract infections and abdominal
      pain. Risk factors include history of pelvic radiation, chemotherapy and
      abdominal surgery, as well as diverticular colonic disease, inflammatory bowel
      disease and traumatic pelvic injury. The paucity of cases reported in the
      literature makes the management of this threatening complication very
      challenging. Conservative treatment has only anecdotally been reported. CASE
      DESCRIPTION: We describe two cases of entero-neovesical fistula with different
      presentation, which both required an immediate surgical treatment. The former
      patient was admitted to the emergency room with faecaluria, complete urinary
      incontinence and fever 2 years after radical cystectomy, and a fistula between
      the Y-shaped neobladder and the bowel anastomosis was detected. He had previously
      undergone chemotherapy because of tumour progression. Undiversion into an ileal
      conduit was required. The latter patient presented with faecaluria 20 days after
      an uneventful radical cystectomy, and a fistula between the Vescica Ileale
      Padovana neobladder and the sigmoid was documented. Treatment included resection
      of the sigmoid with several small diverticula, temporary ileostomy and closure of
      the neobladder fistula. CONCLUSION: Conservative treatment of entero-neovesical
      fistula can be attempted only in patients with small openings in the small bowel
      and no systemic symptoms. In all other cases, surgical treatment with bowel
      resection and either closure of the neobladder opening or undiversion should be
      the preferred option.

PMID- 30118405
TI  - Editorial.

PMID- 30118406
TI  - Abe Baker: Visionary and organizational leader of the American Academy of
      Neurology.
AB  - American neurologist and neuropathologist Abraham Bert (Abe) Baker (1908-1988)
      was instrumental in founding the American Academy of Neurology and served as a
      catalyst for the emergence of neurology as a strong, independent medical
      discipline in the United States in the second half of the twentieth century.
      Baker served as the first president of the Academy from 1948 to 1951. He was also
      instrumental in garnering support for the National Institute of Neurological
      Diseases and Blindness, which was founded in 1950 and later evolved into the
      National Institute of Neurological Disorders and Stroke. Baker's leadership was
      also essential in developing continuing medical education for neurologists at a
      national level and in garnering federal financial support for neurology training
      programs.

PMID- 30118404
TI  - Effects of placental growth factor deficiency on behavior, neuroanatomy, and
      cerebrovasculature of mice.
AB  - Preeclampsia, a hypertensive syndrome occurring in 3-5% of human pregnancies, has
      lifelong health consequences for fetuses. Cognitive ability throughout life is
      altered, and adult stroke risk is increased. One potential etiological factor for
      altered brain development is low concentrations of proangiogenic placental growth
      factor (PGF). Impaired PGF production may promote an antiangiogenic fetal
      environment during neural and cerebrovascular development. We previously reported
      delayed vascularization of the hindbrain, altered retinal vascular organization,
      and less connectivity in the circle of Willis in Pgf-/- mice. We hypothesized Pgf
      /- mice would have impaired cognition and altered brain neuroanatomy in addition
      to compromised cerebrovasculature. Cognitive behavior was assessed in adult Pgf-/
      and Pgf+/+ mice by four paradigms followed by postmortem high-resolution MRI of
      neuroanatomy. X-ray microcomputed tomography imaging investigated the three
      dimensional cerebrovascular geometry in another cohort. Pgf-/- mice exhibited
      poorer spatial memory, less depressive-like behavior, and superior recognition of
      novel objects. Significantly smaller volumes of 10 structures were detected in
      the Pgf-/- compared with Pgf+/+ brain. Pgf-/- brain had more total blood vessel
      segments in the small-diameter range. Lack of PGF altered cognitive functions,
      brain neuroanatomy, and cerebrovasculature in mice. Pgf-/- mice may be a
      preclinical model for the offspring effects of low-PGF preeclampsia gestation.

PMID- 30118407
TI  - Russell DeJong: "The most scholarly neurologist in the Academy".
AB  - Russell Nelson DeJong (1907-1990) became professor and chair of the Department of
      Neurology at the University of Michigan in 1950. A prolific author with more than
      200 publications, DeJong wrote on virtually all areas of neurology. DeJong's
      classic monograph, The Neurologic Examination (1950), grew into an encyclopedic
      volume from lectures he gave to junior and senior medical students; DeJong saw it
      through four editions. He was one of the founders of the American Academy of
      Neurology (AAN), serving as its vice-president from 1961 to 1963 and as the first
      editor-in-chief of its journal, Neurology. Abraham Baker, the driving force
      behind the founding of the AAN, considered DeJong "the most scholarly neurologist
      in the Academy." DeJong was also president of the American Neurological
      Association, president of the American Board of Psychiatry and Neurology,
      president of the American Epilepsy Society, and chairman of the Scientific
      Advisory Board of the National Multiple Sclerosis.

PMID- 30118408
TI  - The founding and early years of the American Academy of Neurology; Dedicated to
      Robert B. Daroff: Mentor, colleague, and friend.

PMID- 30118409
TI  - The Four Horsemen (and their Nags): Recollections of the founding and early years
      of the American Academy of Neurology.
AB  - "The Four Horsemen" was the nickname given to the four neurologists-Abraham
      Baker, Francis Forster, Russell DeJong, and Adolph Sahs-who were most
      instrumental in founding and developing the American Academy of Neurology (AAN)
      beginning around 1948. Forster later humorously added "and their nags" to the
      epithet to reflect the cohesion of the founders and their wives. This article
      presents the personal recollections of these founders from correspondence and
      oral histories. When the AAN was founded, private-practice neurologists and
      residents were excluded from the academically oriented and restrictive American
      Neurological Association (ANA). Baker conceptualized the AAN as an inclusive
      professional society that would accept all neurologists of whatever age and level
      of training, and that would strive to strengthen their knowledge, competencies,
      and skills through continuing medical education and guideline development. Baker
      recruited supportive colleagues to help create and develop the organization.
      Their intention was not to compete with or subvert the ANA, but to offer an
      inclusive professional organization for all neurologists. Nevertheless, their
      efforts produced opposition among ANA members. To defuse the antagonism,
      neurologist Alphonse Vonderahe proposed an influential House-Senate formulation
      of the AAN-ANA relationship, modeled after the U.S. Congress, both as a
      supporting rationale for the AAN and as a conceptual model for the functional
      relationship between the two organizations. The inclusive approach greatly
      augmented the ranks of the fledgling AAN, whereas those of the ANA stayed
      relatively stagnant, with the AAN ultimately becoming the dominant neurological
      society. These neurologic pioneers laid the groundwork for an invigorated, well
      trained, scientifically based specialty of neurology in the second half of the
      twentieth century.

PMID- 30118410
TI  - Pearce Bailey: The "Fifth Horseman" and the National Institute for Neurological
      Diseases and Blindness.
AB  - Pearce Bailey (1902-1976) had an active career focused on the growth and
      development of neurology as a specialty in the post-World War II era. He was a
      founding member of the American Academy of Neurology (AAN) and its second
      president from 1951 to 1953. In 1951, he was also appointed as the first director
      of the National Institute for Neurological Diseases and Blindness (NINDB), which
      is now the National Institute of Neurological Disorders and Stroke. Known as an
      excellent politician, Bailey's role at the NINDB helped bolster the AAN in its
      early days. Prominent neurologists in the AAN, especially A. B. Baker, also
      helped shape the NINDB as early advisors. Bailey continued working to move
      neurology forward globally, including cofounding the World Federation of
      Neurology with Ludo van Bogaert in 1957 and becoming director of the NINDB
      International Research Program in 1959. Bailey retired in 1971, having been
      dubbed by Baker as "one of the smartest politicians that ever came to
      Washington."

PMID- 30118411
TI  - Editorial to special issue: The founding and early years of the American Academy
      of Neurology.

PMID- 30118412
TI  - The founding of neurology as a specialty: The American situation in context.
AB  - With few exceptions, neurology in Europe as well as in the United States emerged
      from internal medicine and psychiatry, and neurology and psychiatry in particular
      have long remained connected in clinical practice and teaching. When the American
      Board of Psychiatry and Neurology (ABPN, 1934) and the American Academy of
      Neurology (AAN, 1948) were founded, the emancipation of neurology as an
      independent specialty was still evolving. During the First International
      Neurological Congress (Berne, Switzerland, in September 1931), a special
      conference was organized on the "Relation of Neurology to General Medicine and
      Psychiatry in Universities and Hospitals of the Various Countries," at which
      representatives from several countries described the situation in their
      countries. Their statements were made around the time of the founding of the ABPN
      and not long before that of the AAN. They show that neurology in most countries
      was still struggling to become independent and only in a few cities flowered as
      an independent specialty. In the second part of this article, specialist
      regulation (training, examination, and certification) in European countries
      (Germany, France, England, and The Netherlands) will be compared to that of the
      ABPN. It appears that Germany was among the early countries where this occurred,
      following the Bremen Arztetag (physicians day) in 1924. Comparable to the
      American situation, it was professionally controlled, in contrast to the French
      state certification, which occurred later. The British specialist regulation was
      much later and more complicated.

PMID- 30118413
TI  - The Four Horsemen and the American Board of Psychiatry and Neurology (ABPN).
AB  - After the gradual introduction of specialties in medicine in the United States
      during the late-nineteenth and early-twentieth centuries, the American Board of
      Psychiatry and Neurology (ABPN) was founded in 1934 to provide specialty
      regulation (training oversight, examination, and certification). The name
      reflects the combined practice of psychiatry and neurology that was still present
      at the time. Directors were nominated by the founding organizations: American
      Psychiatry Association (APA), American Neurological Association (ANA), and the
      Section of Nervous and Mental Diseases of the American Medical Association (AMA).
      Many of the early physicians who were certified by the ABPN did so for psychiatry
      as well as neurology. Neurologist Walter Freeman and psychiatrist Adolph Meyer
      played important roles in the ABPN during the early days. Following the founding
      of the AAN in 1948, neurological practitioners believed the AAN would better
      represent them in the ABPN. At first the ANA appointed AAN members to the ANA
      Council; but after 1972, the AAN could directly nominate directors for the ABPN.
      Despite this situation, the AAN had an important influence in the ABPN from its
      start, as is shown by the fact that all of the key organizational leaders
      responsible for founding the AAN-the "Four Horsemen" (Abraham B. Baker, Russell
      N. DeJong, Francis M. Forster, and Adolph L. Sahs-served as directors of the ABPN
      in the period 1951-1967. The Horsemen were able to change both examination
      practices that became more searching and expansive, and the basic disciplines
      that needed to be studied in detail.

PMID- 30118414
TI  - Francis Forster, the last Horseman: A career in academic neurology.
AB  - American neurologist and epileptologist Francis M. Forster (1912-2006) was the
      last survivor of the "Four Horsemen," a nickname given to the four neurologists
      Forster, Abe Baker, Russell DeJong, and Adolph Sahs-who were most instrumental in
      founding the American Academy of Neurology under Baker's leadership in 1948.
      Forster was a consulting physician for many high-profile patients, including
      President Dwight Eisenhower, President Quirino and Archbishop Reyes of the
      Philippines, Provisional President Lonardi of Argentina, and Cardinal Albert
      Meyer of Chicago. Forster was also an expert witness for the prosecution in the
      trial of Jack Ruby, who killed Lee Harvey Oswald. Forster's greatest legacy,
      though, was as a teacher: During his career as chairman of two robust academic
      neurology departments, he trained more than 100 residents, at least 17 of whom
      went on to become chairmen of neurology departments in the United States, Europe,
      Asia, and South America.

PMID- 30118415
TI  - Joseph Resch and the plea of the practicing neurologists: A postwar neurology
      resident's tale.
AB  - When University of Minnesota neurology resident Joseph A. Resch complained to the
      department director, A. B. Baker, in 1946 about the lack of a professional
      neurological association open to young neurologists like himself, he set into
      motion a chain of events that culminated in the founding of the American Academy
      of Neurology in June of 1948. This provided a supportive professional
      organization for practicing neurologists as the traditional bond between
      neurology and psychiatry was broken during the postwar era. Resch went on to
      become a pivotal figure in the practice of neurology in the Twin Cities and
      succeeded Baker as chairman of the University of Minnesota neurology department.

PMID- 30118416
TI  - Adolph Sahs: A neurologist who could take on still another job.
AB  - Adolph Louis Sahs (1906-1986) became chair of the Department of Neurology at the
      University of Iowa in 1948 and retired in 1974. Through his academic neurology
      organizational skills, coordination of multicenter research on subarachnoid
      hemorrhage, and education of more than 50 neurologists, he helped bring the
      department to national and international prominence. Sahs was one of the founders
      of the American Academy of Neurology. He served as president of the Academy, the
      American Neurological Association, and the American Board of Psychiatry and
      Neurology. Sahs was known as a neurologist who could always take on yet another
      job in the interest of the specialty.

PMID- 30118417
TI  - How Should Refusal of Tracheostomy as Part of an Adolescent's Perioperative
      Planned Intubation Be Regarded?
AB  - Here we present a case of a patient in terminal respiratory failure refusing to
      consent to emergent tracheostomy in the setting of an anticipated difficult
      intubation. We examine ethical concerns that arise from deviations from the
      standard of care in the operative setting and the anesthesiologist's sense of
      culpability. Finally, we will review the ethical arguments and guidelines that
      support anesthesiologists' participation in palliative operative procedures when
      limitations on resuscitation are in place.

PMID- 30118418
TI  - How Should Physicians Care for Dying Patients with Amyotrophic Lateral Sclerosis?
AB  - We discuss physician aid in dying, euthanasia, and other dimensions of palliative
      care decision making and define relevant terms raised by this case of a dying
      patient with amyotrophic lateral sclerosis in Washington State who is unable to
      self-administer a lethal prescription. We then present a concrete framework that
      clinicians can directly apply when faced with difficult cases such as this one.
      We outline how exploring motivations, obtaining informed consent, defining goals,
      and examining alternatives can help guide physicians like the one in this case.
      We conclude by summarizing one way in which physicians might balance these issues
      while still remaining within the constraints of the law.

PMID- 30118419
TI  - Should Physicians New to a Case Counsel Patients and Their Families to Change
      Course at the End of Life?
AB  - Although new cancer therapies have changed the prognosis for some patients with
      advanced malignancies, the potential benefit for an individual patient remains
      difficult to predict. This uncertainty has impacted goals-of-care discussions for
      oncology patients during critical illness. Physicians need to have transparent
      discussions about end-of-life care options that explore different perspectives
      and acknowledge uncertainty. Considering a case of a new physician's objections
      to an established care plan that prioritizes comfort measures, we review
      physician practice variation, clinical momentum, and possible moral objections.
      We explore how to approach such conflict and discuss whether and when it is
      appropriate for physicians new to a case to challenge established goals of care.

PMID- 30118420
TI  - How Should Physicians Manage Organ Donation after the Circulatory Determination
      of Death in Patients with Extremely Poor Neurological Prognosis?
AB  - Organ donation after the circulatory determination of death (DCDD) accounts for a
      growing percentage of deceased organ donations. Although hospital DCDD protocols
      stipulate donor death determination, some do not adhere to national guidelines
      that require mechanical, not electrical, asystole. Surrogate decisions to
      withdraw life-sustaining therapy should be separated from decisions to donate
      organs. Donor families should be given sufficient information about the DCDD
      protocol and its impact on the dying process to provide informed consent, and
      donors should be given proper palliative care during dying. An unresolved ethical
      question is whether and how donor consent should be seen as authorizing
      manipulation of a living donor during the dying process solely for to benefit of
      the organ recipient.

PMID- 30118421
TI  - Four Communication Skills from Psychiatry Useful in Palliative Care and How to
      Teach Them.
AB  - Palliative care and psychiatry share a number of the same priorities, including
      careful attention to communication skill development. In this article, we
      identify 4 communication skills helpful in both fields: (1) attending to
      countertransference, (2) practicing active listening and active reflection, (3)
      remaining silent and neutral, and (4) naming the emotion. We then describe
      strategies for teaching these skills.

PMID- 30118422
TI  - Which Critical Communication Skills Are Essential for Interdisciplinary End-of
      Life Discussions?
AB  - Conversations about dying and end-of-life (EOL) care are the most challenging of
      all communication scenarios. These conversations include discussions about
      diagnosis and prognosis, treatment goals, and EOL wishes, goals of care, and
      plans for the future. Research has identified critically important skills
      involved in holding such conversations, and protocols have been established that
      can assist those discussing these important issues. Often several discussions and
      professionals from multiple disciplines are needed to ensure that EOL
      conversations are effective and comprehensive. In this article, we review what is
      known about the skills and strategies necessary for meaningful and effective EOL
      conversations and emphasize the valuable role of interdisciplinary approaches to
      these discussions. Advanced care planning (ACP), which refers to patient
      decisions about desired care should the patient lose decisional capacity, is
      included as a type of EOL discussion in this article.

PMID- 30118423
TI  - Clinical Momentum as One Reason Dying Patients Are Underserved in Acute Care
      Settings.
AB  - "Clinical momentum" refers to the curious expansion of interventions applied to
      patients in the intensive care unit (ICU) without pause or design, leading to
      extensions of care that can violate patient wishes and distress clinicians. In
      this article, clinical momentum is placed in a wider context that includes
      ritual, reimbursement patterns, and actor network theory. These contextual
      features help motivate understanding of one way in which dying patients are
      underserved in intensive care settings. Suggestions are made for clinician
      interaction with families under these circumstances.

PMID- 30118424
TI  - Should There Be a Disclosure Mandate for Physicians Caring for Perinatally
      Infected Adolescents Who Don't Know Their HIV Serostatus?
AB  - With advances in antiretroviral therapies, perinatally infected children are now
      living with HIV well beyond adolescence. Parents and health care practitioners
      thus face the challenge of deciding how best to disclose positive serostatus to
      children living with HIV. Although many adolescents living with HIV are sexually
      active, parents often delay disclosure, which presents US physicians with an
      ethical dilemma because there is no legal requirement to follow clinical
      guidelines recommending disclosure prior to adolescence. When they become adults,
      US adolescents could face criminal penalties if they fail to disclose their
      positive serostatus to needle-sharing or sex partners despite there being no
      legal mandates to ensure that adolescents are first properly informed of their
      own diagnoses. We argue that there is an urgent need to bridge this gap between
      adolescent and adult HIV serostatus disclosure policies.

PMID- 30118425
TI  - For People Dying to Talk, It Finally Pays to Listen with Reimbursable Advance
      Care Planning.
AB  - Whether at the beginning, middle, or end of life, health care delivery choices
      abound. Yet only recently have conversations specifically regarding preferences
      for care at the end of life become a reimbursable intervention, deemed equivalent
      in importance to a medical procedure. Quite distinct from other procedures, in
      which expectations for outcomes are explicit and measurable, outcomes have been
      left intentionally vague for advanced care planning (ACP) conversations. This
      article will explore the inherent challenges of and opportunities for developing
      formalized outcomes, methods of measurement, and training to ensure excellence in
      the performance of ACP conversation procedures. Whether at the beginning, middle,
      or end of life, health care delivery choices abound. Yet only recently have
      conversations specifically regarding preferences for care at the end of life
      become a reimbursable intervention, deemed equivalent in importance to a medical
      procedure. Quite distinct from other procedures, in which expectations for
      outcomes are explicit and measurable, outcomes have been left intentionally vague
      for advanced care planning (ACP) conversations. This article will explore the
      inherent challenges of and opportunities for developing formalized outcomes,
      methods of measurement, and training to ensure excellence in the performance of
      ACP conversation procedures.

PMID- 30118426
TI  - How Should We Enhance the Process and Purpose of Prognostic Communication in
      Oncology?
AB  - We propose that effective prognostic communication requires attention to the
      process and purpose of communication, where purpose represents the will and
      process the ability to communicate. Prognostic communication has historically
      challenged clinicians and patients. Few interventions have been developed to
      improve prognostic communication, and those that have been developed largely
      target the process of communication. We argue that more work is needed to address
      the purpose of prognostic communication, because the first step in all effective
      communication is desiring to communicate well. In developing communication
      interventions, investigators should be thoughtful about the audience they are
      targeting, the goals of the intervention, and the feasibility of disseminating
      and implementing the intervention in busy health care systems with limited
      resources.

PMID- 30118427
TI  - How Do Medicalization and Rescue Fantasy Prevent Healthy Dying?
AB  - Before antibiotics, cardiopulmonary resuscitation (CPR), and life-sustaining
      technologies, humans had little choice about the timing and manner of their
      deaths. Today, the medicalization of death has enabled patients to delay death,
      prolonging their living and dying. New technology, the influence of the media,
      and medical professionals themselves have together transformed dying from a
      natural part of the human experience into a medical crisis from which a patient
      must be rescued, often through the aggressive extension of life or through its
      premature termination. In this paper, we examine problematic forms of rescue
      medicine and suggest the need to rethink medicalized dying within the context of
      medicine's orientation to health and wholeness.

PMID- 30118428
TI  - Do No Harm.
AB  - After a goals-of-care conversation, this patient's chart listed his status as
      "full-code." As shown in this image, resuscitation was initiated for a 92-year
      old man with metastatic malignancy after being found pulseless by the rounding
      team.

PMID- 30118429
TI  - Unrepresent.
AB  - This image represents a physician unilaterally completing a do-not-resuscitate
      order for an unrepresented patient.

PMID- 30118430
TI  - Cruel Carousel: The Grim Grind of "Compassionate" Dialysis.
AB  - In this graphic narrative, a clinician illustrates an experience of caring for an
      undocumented patient suffering from end-stage renal disease (ESRD). Cruel
      Carousel tells one of the stories that most profoundly shaped the author's own
      views on health care for undocumented immigrants. Graphic narrative was chosen to
      tell this story because words alone couldn't capture the patient's experience or
      the author's distress about what happened to him.

PMID- 30118431
TI  - Resilience.
AB  - When I told people I was pursuing a career in medicine, the statistics of female
      physician suicide were mentioned. When I professed an interest in surgery, I was
      told to choose a specialty for lifestyle, because as a woman I would need a
      career that would allow me to raise my future children. All around me, I have
      been assaulted by doubt, as senior physicians whisper to students of my
      generation to turn away while we still can.

PMID- 30118432
TI  - The Role of Hope, Compassion, and Uncertainty in Physicians' Reluctance to
      Initiate Palliative Care.
AB  - This article addresses whether physicians' close ties to their patients might
      play an unexamined role in their reluctance to initiate palliative care. In cases
      characterized by uncertainty, physicians' emotional investment in their patients
      and patients' families might unduly promote decisions to continue aggressive
      treatment rather than transition to comfort care. Continued evaluation and
      communication of patient status, including scheduled objective consultations, can
      align compassionate actions with patients' best interests. This argument and
      analysis are based on a case of new onset refractory status epilepticus (NORSE).

PMID- 30118433
TI  - Specialized Palliative and Hospice Care and the Importance of Mourning Our
      Nation's Veterans.
AB  - One aspect of palliative medicine that has been underexplored is the perspective
      of veterans either facing critical life-limiting illness or at the end of life.
      The needs of veterans differ not only because military culture affects how
      veterans cope with their illness but also because exposure-related factors
      (combat and environmental) differ between military branches. In this paper, we
      describe two cases involving end-of-life care for veterans with combat trauma and
      describe individualized approaches to their care.

PMID- 30118435
TI  - First break psychosis in a young military veteran with cannabis use disorder: an
      educational case report.

PMID- 30118434
TI  - Pollution and Global Health - An Agenda for Prevention.
AB  - SUMMARY: Pollution is a major, overlooked, global health threat that was
      responsible in 2015 for an estimated 9 million deaths and great economic losses.
      To end neglect of pollution and advance prevention of pollution-related disease,
      we formed the Lancet Commission on Pollution and Health. Despite recent gains in
      understanding of pollution and its health effects, this Commission noted that
      large gaps in knowledge remain. To close these gaps and guide prevention, the
      Commission made research recommendations and proposed creation of a Global
      Observatory on Pollution and Health. We posit that successful pollution research
      will be translational and based on transdisciplinary collaborations among
      exposure science, epidemiology, data science, engineering, health policy, and
      economics. We envision that the Global Observatory on Pollution and Health will
      be a multinational consortium based at Boston College and the Harvard T.H. Chan
      School of Public Health that will aggregate, geocode, and archive data on
      pollution and pollution-related disease; analyze these data to discern trends,
      geographic patterns, and opportunities for intervention; and make its findings
      available to policymakers, the media, and the global public to catalyze research,
      inform policy, and assist cities and countries to target pollution, track
      progress, and save lives. https://doi.org/10.1289/EHP3141.

PMID- 30118436
TI  - Gynecological problems among adolescent girls in a tertiary care centre of South
      Andaman district.

PMID- 30118437
TI  - Illness beliefs of adolescents with CFS and their parents: the perceived causes
      of illness and beliefs about recovery.

PMID- 30118438
TI  - Knowledge of emergency management of avulsed tooth among intern dental students:
      a questionnaire based study.

PMID- 30118439
TI  - A new inverse planning formalism with explicit DVH constraints and kurtosis-based
      dosimetric criteria.
AB  - In inverse planning processes of radiotherapy, dose-volume histograms (DVH) have
      been commonly used as a measure of plan quality. The exact mathematical
      formulation of DVHs involves binary variables and is therefore intrinsically
      nonconvex. In view of the resulting computational intractability, existing
      treatment planning systems adopt convex surrogate models that involve many
      parameters. Manual parameter tweaking is then required to determine reasonable
      values for those parameters in order to generate plans that meet the target DVHs.
      However, conventional convex formulations for inverse planning entails non
      trivial differences from an exact formulation and, therefore, provide only very
      limited control over the DVHs. In view of this limitation, this paper presents a
      new formulation that combines a novel folded concave penalty (FCP)-based
      constraint and a new kurtosis-based optimization criterion. The former presents a
      much sharper approximation to the exact DVH constraints than the existing
      counterparts, and the latter penalizes the occurrence of hot and cold spots in
      dose distributions. We investigated the effectiveness of the proposed planning
      formulations on three head-and-neck cases in comparison with conventional DVH
      based formulations. Significant outperformance in terms of better distributed
      doses-at-volume was achieved through the proposed scheme.

PMID- 30118440
TI  - Design and performance of the micro-dose calibrator.
AB  - A new class of dose calibrator called a micro-dose calibrator, designed to
      measure radioactivity rates in the range between 1 kBq up to 370 kBq, has been
      designed and an 8 NaI(Tl)/photo multiplier tube (PMT) module prototype built to
      evaluate its performance. The design of the micro-dose calibrator is based on the
      concept of a segmented well counter. By segmenting a single crystal well counter
      into multiple crystals or segments, with each segment operated and read out
      independently, one can extend the operational range of a standard single crystal
      well counter while maintaining its accuracy and spectrographic capabilities. The
      micro-dose calibrator is operated in N-fold coincidence mode to ensure that a
      single radioactive decay resulting in multiple segments detecting gamma ray
      events are counted as a single decay. The N fold coincidence detection is
      achieved using a pipeline coincidence processing algorithm implemented in
      software as part of a multi-threaded acquisition system. A tri-functional model
      pulse pileup dead time correction is applied to extend the operational range of
      the micro-dose calibrator. The micro-dose calibrator achieved an operation range
      between 1 kBq up to 3.4 MBq for 18F with a 1% linearity precision using a 60 s
      integration time window. Over a 9 d period, a daily count rate measure of a 137Cs
      point source had a coefficient of variation of 0.17% with only one high voltage
      calibration performed on day 0. The central 20 mm up to 35 mm axial length in the
      sample well showed less than 1% change in count rate depending on the
      radionuclide. Using a 0.5 ml insulin syringe, a volume of dose between 0.13 ml up
      to 0.50 ml showed less than 1% deviation from volumetric linearity. A 20 cc
      scintillation vial showed similar volumetric linearity performance for
      radionuclide solution volumes between 4 cc up to 20 cc.

PMID- 30118442
TI  - Attachment Orientation and Relationships With Physicians and Nurses Among Israeli
      Patients With Advanced Cancer.
AB  - OBJECTIVES: To examine the association between attachment orientation and
      relationships with physicians and nurses among Israeli patients with advanced
      cancer. SAMPLE &AMP; SETTING: 52 patients with advanced cancer during active
      oncologic treatment. METHODS &AMP; VARIABLES: Eligible patients who agreed to
      participate in the study completed the Experience in Close Relationships Scale,
      Working Alliance Inventory-Short Revised, and a list of topics, which were
      defined by the research team as central and common to patients' coping. RESULTS:
      A correlation was found between avoidant attachment orientation and working
      alliance with nurses. In addition, patients' attachment orientation was found to
      be correlated with the type of topics they chose to share with the staff.
      IMPLICATIONS FOR NURSING: Knowledge regarding the theoretical concepts of
      attachment orientation may assist nurses in providing tailored and beneficial
      communication patterns with patients.

PMID- 30118441
TI  - Inhibition of C-X-C Motif Chemokine 10 (CXCL10) Protects Mice from Cigarette
      Smoke-Induced Chronic Obstructive Pulmonary Disease.
AB  - BACKGROUND Chronic obstructive pulmonary disease (COPD) is a type of obstructive
      lung disease characterized by long-term breathing problems and poor airflow. COPD
      can progress to persistent decline of pulmonary function. This study explored the
      effect of CXCL10 on COPD induced by cigarette smoke (CS) and its underlying
      mechanism. MATERIAL AND METHODS Wild-type (WT) mice were randomly assigned into 3
      groups: the control group, the CS group, and the intervention group. Mice in the
      CS group were exposed to CS and mice in the CXCL10 group were exposed to CS and
      CXCL10 neutralizing antibody. At 24 h after the last CS exposure, body weight and
      lung functions of each mouse were recorded. Mice were then anesthetized for
      collecting bronchoalveolar lavage fluid (BALF) and lung tissues. Levels of
      interleukin-6 (IL-6), keratinocyte chemotactic factor (KC), and monocyte
      chemoattractant protein-1 (MCP-1) in supernatant and lung homogenate were
      detected by ELISA and real-time PCR (RT-PCR), respectively. For in vitro
      experiments, human bronchial epithelial cells 16HBE were stimulated with
      different concentrations of cigarette smoke extract (CSE) and CXCL10. Cell
      viability and levels of inflammatory cytokines in the cell supernatant were
      detected by Cell Counting Kit-8 (CCK-8) and ELISA assay, respectively. RESULTS
      Our data showed significant weight loss and reduction of lung functions in mice
      in the CS group compared with those in the control group and intervention group.
      Increased levels of IL-6, KC, and MCP-1 in BALF and lung homogenate were observed
      in mice in the model group compared to those in the control group and
      intervention group. In vitro experiments also confirmed that CXCL10-neutralizing
      antibody can inhibit CSE-induced cell necrosis and activation of inflammatory
      cytokines. CONCLUSIONS Inhibited CXCL10 protects against COPD progression by
      decreasing secretion of inflammatory factors, which provides a new direction for
      the clinical prevention and treatment of COPD.

PMID- 30118443
TI  - Symptoms, Mobility and Function, and Quality of Life in Adults With Acute
      Leukemia During Initial Hospitalization.
AB  - OBJECTIVES: To examine longitudinal symptoms, mobility and function, and quality
      of life (QOL) in adults newly diagnosed with acute leukemia. SAMPLE &AMP;
      SETTING: 55 adults undergoing induction chemotherapy at the University of North
      Carolina Lineberger Comprehensive Cancer Center and the Duke Cancer Institute.
      METHODS &AMP; VARIABLES: A prospective, longitudinal study with measures of
      mobility and function, global physical and mental health, cancer-related fatigue,
      anxiety, depression, sleep disturbance, pain intensity, and leukemia-specific QOL
      was conducted. Data were analyzed using descriptive statistics, linear mixed
      modeling, and one-way analysis of variance. RESULTS: 49 adults with acute
      leukemia completed assessments during hospitalizations. Global mental health and
      pain intensity did not change significantly. Global physical health significantly
      improved. Fatigue, anxiety, depression, and sleep disturbance decreased
      significantly. QOL increased significantly. IMPLICATIONS FOR NURSING: The
      significant decrease in anxiety and fatigue during hospitalization may be
      attributable to understanding of the disease process, familiarity with the staff,
      and ability to communicate concerns.

PMID- 30118444
TI  - Feasibility Studies: What They Are, How They Are Done, and What We Can Learn From
      Them.
AB  - Nursing clinical research is a growing field, and as more nurses become engaged
      in conducting clinical research, feasibility studies may be their first
      encounter. Understanding what they are, how to conduct them, and the importance
      of properly reporting their outcomes is vital to the continued advancement of
      nursing science.

PMID- 30118445
TI  - Well-Being of Child and Family Participants in Phase 1 Pediatric Oncology
      Clinical Trials.
AB  - PROBLEM IDENTIFICATION: Pediatric oncology phase 1 clinical trials (P1Ts) are
      essential to developing new anticancer therapies; however, they raise complex
      ethical concerns about balancing the need for this research with the well-being
      of participating children. The purpose of this integrative review was to
      synthesize and appraise the evidence of how P1T participation, which begins with
      consent and ends with the transition off the P1T, can affect the well-being
      (either positively or negatively) of children with cancer. The Resilience in
      Individuals and Families Affected by Cancer Framework, which has an outcome of
      well-being, was used to synthesize findings. LITERATURE SEARCH: Articles on the
      experiences of child (n = 21) and adult (n = 31) P1T participants were identified
      through systematic searches. DATA EVALUATION: Articles were evaluated on rigor
      and relevance to P1T participant experiences as high, medium, or low. SYNTHESIS:
      Minimal empirical evidence was found regarding the effect of P1T participation on
      the well-being of children with cancer. Adult P1T participant experiences provide
      insights that could also be important to children's P1T experiences. IMPLICATIONS
      FOR PRACTICE: To achieve a balanced approach in P1T consent discussions, nurses
      and healthcare providers who work with children considering participation in a
      P1T should share the potential effect of participation on participants' well
      being.

PMID- 30118446
TI  - Oncology Nurses' Knowledge of Pharmacogenomics Before and After Implementation of
      an Education Module.
AB  - OBJECTIVES: To assess the efficacy of an interactive continuing education module
      in improving knowledge of pharmacogenomics in oncology nursing practice. SAMPLE
      &AMP; SETTING: 434 inpatient and outpatient oncology nurses from a large teaching
      hospital in Florida and oncology nurses who practice in North Carolina. METHODS
      &AMP; VARIABLES: An interactive continuing education module was created based on
      key information elicited from a focus group of inpatient and outpatient oncology
      nurses regarding their lack of knowledge on pharmacogenomics. A pre-/post-test
      design was implemented. Purposive sampling of oncology nurses was used. RESULTS:
      The mean pretest score was 72.7 and the post-test score was 85.9. A statistically
      significant difference was found between these scores. No difference in scores
      were found between the oncology nurses employed at urban hospitals compared to
      nurses at community hospitals or outpatient settings. IMPLICATIONS FOR NURSING:
      Educational opportunities for pharmacogenomics should be threaded throughout
      nursing competencies. The continuing education module in the current article has
      been shown to significantly improve oncology nurses' knowledge of genomic and
      pharmacogenomic information.

PMID- 30118447
TI  - Food Safety Knowledge and Self-Reported Food-Handling Practices in Cancer
      Treatment.
AB  - OBJECTIVES: To explore awareness of foodborne infection risk during chemotherapy
      treatment, to assess knowledge of risk-reducing food safety practices in patients
      with cancer and their family caregivers, and to determine self-reported food
      handling practices. SAMPLE &AMP; SETTING: A convenience sample of 121 patients
      receiving chemotherapy and 51 family caregivers of patients receiving
      chemotherapy in the United Kingdom recruited in the community and using online
      advertising. METHODS &AMP; VARIABLES: Participants completed a self-report
      questionnaire to determine food safety knowledge and self-reported food-handling
      practices. RESULTS: Although patients receiving chemotherapy and family
      caregivers reported awareness of food safety practices, self-reported practices
      indicated that potentially unsafe practices may be used in relation to
      temperature control, handwashing, safe cooking, and adherence to use-by dates.
      Such practices may increase the risk of foodborne illness to patients receiving
      chemotherapy treatment. IMPLICATIONS FOR NURSING: Nursing research is required to
      explore the food safety training and awareness of healthcare providers. Highly
      focused and specifically targeted food safety interventions need to be developed
      and delivered to increase awareness and to implement food safety practices.

PMID- 30118448
TI  - Nurse-Delivered Symptom Assessment for Individuals With Advanced Lung Cancer.
AB  - OBJECTIVES: To assess an intervention derived from self-regulation theory (SRT)
      to promote well-being for individuals with advanced lung cancer. SAMPLE &AMP;
      SETTING: 45 adults with advanced lung cancer who were receiving chemotherapy at
      an ambulatory cancer center. METHODS &AMP; VARIABLES: Participants were
      randomized to the intervention group or usual care control group. Feasibility
      assessment focused on recruitment, retention, design, methods, and fidelity.
      Outcome measures of quality of life, symptoms, and distress were collected at
      four time points. The main research variables were symptoms, quality of life, and
      distress. RESULTS: The participation rate was 79%, and the retention rate was
      62%. Participant loss was most often because of progressive disease and occurred
      early in the study. High fidelity was noted for delivery of the intervention as
      planned and outcome data collection by telephone. The mean number of
      interventions delivered was 5.5 of a planned 8. A high level of acceptability was
      reported for participants completing the intervention. IMPLICATIONS FOR NURSING:
      Although delivering the SRT-derived intervention with fidelity was possible,
      feasibility findings do not warrant intervention replication in this population.

PMID- 30118449
TI  - The Context of Patients' Lives.
AB  - I try to touch base with the clinic nurses each day before patients and
      physicians (in that order) start arriving and the usual busyness of the day takes
      over. A recent early morning conversation centered on one nurse's frustration
      with the spouse of a man who had been treated in another city and who was now
      under the care of a physician at our clinic. The woman had been calling the nurse
      repeatedly since her husband had returned home after the procedure. He was having
      complications, and she wanted something to be done about this immediately. The
      nurse was receiving text and email messages from the physician, who was also
      being contacted by the man's spouse, and his frustration was doubling up the
      effect on the nurse. The physician had agreed to provide follow-up care for this
      man and, frankly, I was somewhat surprised at the fuss this was creating.

PMID- 30118450
TI  - Feelings of Disenfranchisement and Support Needs Among Patients With Thyroid
      Cancer.
AB  - PURPOSE: To offer a better understanding of the experiences, preferences, and
      needs of patients with thyroid cancer. PARTICIPANTS &AMP; SETTING: 17 patients
      with thyroid cancer receiving treatment at a university-affiliated hospital in
      Montreal, Quebec, Canada. METHODOLOGIC APPROACH: Interviews were conducted with
      patients, and descriptive phenomenology was used to explore patients' lived
      experience. FINDINGS: Coping with uncertainty was a major theme that emerged from
      interviews, with some of the main concerns being difficult treatment decisions,
      long surgery wait times, and fears about surgical complications, potential
      metastases, and death. Study participants reported that without a nurse and an
      interprofessional team, they would be lost in a system they believed minimized
      their illness and offered few resources to support them in a time of crisis.
      IMPLICATIONS FOR NURSING: Nurses must understand how the needs of individuals
      with thyroid cancer are often overlooked because of the good prognosis associated
      with the disease and should work to meet these information and support needs.

PMID- 30118451
TI  - Response to "Taking Photos of Presentations: Dissemination or Distraction?"
AB  - I would like to thank Anne Katz, PhD, RN, FAAN, for her thoughtful editorial in
      the July 2018 issue of Oncology Nursing Forum. At least twice, that I am aware
      of, someone has used my slides without my permission. The first time happened
      about 10 years ago. I gave an educational program on the fundamentals of
      hereditary cancer syndromes at a regional conference for oncology nurses. I
      provided a detailed outline for note-taking and a list of references and
      resources. On one slide, there was a picture of my entire extended family at our
      cabin in a remote area of the Ozarks in Missouri, as well as several other photos
      that I had taken of my daughters and dog. Only I had access to those
      photos.&nbsp.

PMID- 30118452
TI  - Impact of Oral Anticancer Medication From a Family Caregiver Perspective.
AB  - PURPOSE: To describe how family caregivers of patients receiving oral anticancer
      medication (OAM) may affect family caregivers' lives and determine what support
      caregivers need to manage OAM in the home successfully. PARTICIPANTS &AMP;
      SETTING: Family caregivers of individuals with cancer prescribed OAM recruited
      from oncology clinics in the Midwest region of the United States. METHODOLOGIC
      APPROACH: Focus group methodology was used to elicit caregivers' perspectives.
      Sessions were audio recorded and transcribed verbatim. Qualitative analysis used
      a constant comparative approach. FINDINGS: Themes specific to OAM treatment were
      convenience, safe handling, financial worries, and medical impact of OAM
      treatment course. IMPLICATIONS FOR NURSING: Providing support and educating
      caregivers on preparation, administration and safe handling, precautions for the
      handling of patient bodily fluids, potential for treatment interruptions, and
      financial assistance and resources for OAM may bolster effective caregiving in
      home environments.

PMID- 30118453
TI  - Feasibility of a Telemedicine-Delivered Cognitive Behavioral Therapy for Insomnia
      in Rural Breast Cancer Survivors.
AB  - OBJECTIVES: To evaluate a nurse-led, telemedicine-delivered cognitive behavioral
      therapy for insomnia (CBTI) in rural breast cancer survivors (BCSs). SAMPLE &AMP;
      SETTING: 18 BCSs diagnosed with stage I-III breast cancer in the rural western
      United States. METHODS &AMP; VARIABLES: In this prospective, pre-/post-test,
      quasiexperimental feasibility pilot trial, BCSs attended six weekly sessions of
      CBTI via Internet videoconference. Feasibility was assessed using recruitment and
      acceptability of the intervention. Primary outcomes were diary-based sleep
      efficiency (SE), sleep latency (SL), total sleep time, wake after sleep onset,
      and number of nightly awakenings; secondary outcomes included quality of life
      (QOL), mental health, and daily functioning. RESULTS: Following the intervention,
      participants reported improvements in sleep outcomes, including SE and SL. QOL
      and daily functioning improved, but anxiety and depression did not. IMPLICATIONS
      FOR NURSING: Nurse-led, telemedicine-delivered CBTI for rural BCSs is feasible
      and may be effective in managing insomnia. Additional research is needed to
      determine widespread effectiveness and best practices for dissemination and
      implementation.

PMID- 30118454
TI  - Support Needs of People With Head and Neck Cancer Regarding the Disease and Its
      Treatment.
AB  - OBJECTIVES: To provide insight into people's experiences in dealing with the
      consequences of head and neck cancer (HNC) in daily life and their needs for self
      management support. SAMPLE &AMP; SETTING: 13 people with HNC who were
      successfully treated in the Department of Radiation Oncology at the Erasmus MC
      Cancer Institute in Rotterdam, the Netherlands. METHODS &AMP; VARIABLES: Two
      focus groups and six individual interviews; data were analyzed with directed
      content analysis. RESULTS: Most patients wished to receive professional support
      for dealing with post-treatment consequences. Apart from physical complaints,
      patients had difficulties in dealing with the emotional aspects of HNC and its
      treatment and struggled with building self-confidence to move on with their
      lives. Patients mentioned the importance of relatives being there for them but
      complained that their needs were not always met. Support from fellow patients was
      valued for their empathetic capacity. IMPLICATIONS FOR NURSING: Nurses must
      provide self-management support that meets people's integral needs inherent in
      living with the consequences of HNC, particularly in the initial post-treatment
      period. Practical interventions could be useful.

PMID- 30118455
TI  - [Pediatric gastroenterology remains in force].

PMID- 30118456
TI  - Percutaneous endoscopic gastrostomy in children: a single center study at
      Tertiary hospital Iran.
AB  - INTRODUCTION: The aim of this study was to evaluate complications after
      percutaneous endoscopic gastrostomy among children who underwent percutaneous
      endoscopic gastrostomy in Nemazee hospital. MATERIALS AND METHODS: All children
      who underwent percutaneous endoscopic gastrostomy were included in the current
      study. Place of the study was department of pediatric gastroenterology of Nemazee
      children hospital of Shiraz university of medical sciences. Duration of the study
      was 5 year starting from 2008. All drugs such as aspirin, NSAIDS, and heparin
      were discontinued 1-7 days before procedures. All patients were kept NPO 6-8
      hours before procedure according to the age. Single dose antibiotic was
      prescribed for all cases before procedure. During procedure, all patients were
      sedated using propofol and or midazolam. Some patients required intubation.
      RESULTS: Of 39 cases who underwent PEG, 4 (10.2%) patients showed complication.
      The most common indication for PEG insertion were neurologic problem (84.6%) and
      metabolic disease (10.2%). Of our patients, 84.6% of the cases had the weight
      below third percentile. CONCLUSION: The most common indication for percutaneous
      endoscopic gastrostomy was cerebral palsy. The complication rate in our study was
      10.2%. Celulitis was the most common complication.

PMID- 30118457
TI  - Effect of sequential therapy on treatment of Helicobacter pylori infection in
      children.
AB  - BACKGROUND: Helicobacter pylori infection which plays a major role in the
      etiology of chronic gastritis and duodenal ulcers in children and adults is one
      of the commonest chronic infection worldwide. Cure of the infection leads to
      healing of gastric inflammation and prevention of peptic ulcer. OBJECTIVE: The
      aim of this study was to evaluate the efficacy of the sequential therapy for
      treatment of Helicobacter pylori infection. MATERIALS AND METHODS: In this study,
      40 children with symptoms of H. Pylori that the infection was proved by endoscopy
      and biopsy and rapid urease test (UBT) were enrolled, and received sequential
      therapy (Lansoprazol, Amoxicillin) for 5 days and (Lansoprazol, Metronidazole and
      Clarithromycin) for next 5 days. The eradication rate of therapy was evaluated by
      stool antigen test 6 weeks after completion of therapy. This study was carried
      out in Pediatric Gastroenterology Clinic of Shiraz University of Medical
      Sciences, Shiraz, Iran. This study was approved by ethic committee of Shiraz
      University of Medical Sciences. RESULTS: Forty children with mean age of (10.8+/
      4 years) were evaluated. The most common symptom on first admission was
      epigastric pain (82.5%), with mean duration of symptoms (16+/-14.5 month). The
      most common endoscopic findings was redness and erosion of the antrum (55%) and
      the most pathologic findings was chronic gastritis (77.5%). The most drug adverse
      effect was nausea (22.5%). The eradication rate of sequential therapy was 82.5%.
      CONCLUSION: Eradication rate of sequential therapy was 82.5% among our cases.

PMID- 30118459
TI  - [Validation of an ammonia breath test for the diagnosis of Helicobacter pylori
      infection in patients with dyspepsia at Hospital Cayetano Heredia].
AB  - : Objetive: To determine the diagnostic validity of an ammonia breath test for
      Helicobacter pylori infection in patients who undergo an upper gastrointestinal
      endoscopy at Hospital Cayetano Heredia. MATERIAL AND METHODS: From April to
      December 2014, 155 patients were evaluated with the ammonia breath test and
      compared with a histological evaluation of the gastric biopsies as the gold
      standard. Data were evaluated using Microsoft Excel and STATA 14 to build a ROC
      curve. RESULTS: The patients were predominantly female (71%), with a median age
      of 53 years (18-84) and a Helicobacter pylori prevalence of 51.6%. The ammonia
      breath test, when compared to the gastric biopsy has a 70% sensitivity, 36%
      specificity, 53.8% positive predictive value, 36% negative predictive value, 1.15
      positive likelihood ratio and 0.75 negative likelihood ratio. According to the
      ROC curve, there is not an optimal cut off value and the area under the curve was
      0.5517. CONCLUSIONS: The ammonia breath test evaluated on this study does not
      have diagnostic accuracy and is not recommended as a diagnostic tool for
      Helicobacter pylori infection.

PMID- 30118458
TI  - [Irritable bowel syndrome subtypes and characteristics in children from Panama,
      Ecuador,El Salvador, Nicaragua and Mexico].
AB  - INTRODUCTION: Few pediatric studies classify the irritable bowel syndrome (IBS)
      subtypes. OBJECTIVE: To describe the characteristics and subtypes of IBS in
      children from Panama, Ecuador, El Salvador, Nicaragua and Mexico. MATERIAL AND
      METHODS: Prevalence study performed in children between 8 and 18 years of age
      with a diagnosis of IBS. The children answered the Questionnaire for Pediatric
      Gastrointestinal Symptoms Roma III for Schoolchildren and Adolescents (QPGS-III)
      to identify functional gastrointestinal disorders. Variables such as age and sex
      were taken into account. The subtypes of IBS were classified in IBS with
      constipation (IBS-c), with diarrhea (IBS-d), mixed (IBS-m) and without subtype
      (IBS-ss). Statistical analysis included measures of central tendency, two-tailed
      student t-test, chi-square test, and Fisher's exact test, with a significant
      p<0.05. RESULTS: We included 79 children (54.4% female, 12.1+/-2.1 years)
      presenting IBS-ss in 55.7%, IBS-c in 15.2%, IBS-m in 15.2% and SII-d in 13.9%.
      Severe pain predominated most of the day and with mucous stools; possible
      associations for IBS-d school and sex. CONCLUSION: After IBS-ss, the IBS-e, IBS-d
      and IBS-m are similar, being the possible risk factors for IBS-d, the public
      school and the female gender.

PMID- 30118460
TI  - [Clinical, pathological and microbiological association of Helicobacter pylori in
      gastric biopsies in the department of Caldas-Colombia].
AB  - OBJECTIVE: To establish the clinical, pathological and microbiological
      association of Helicobacter pylori in gastric biopsies in a population of the
      department of Caldas (Colombia). MATERIALS AND METHODS: We included 72 patients,
      who were referred for digestive endoscopy to the San Marcel clinic in the city of
      Manizales during the second half of 2015; two biopsies of the antrum and two of
      the body of the stomach were taken for histopathological study and
      microbiological culture. Data were submitted to descriptive and relational
      statistical procedures. RESULTS: H. pylori was found in 47.2% by histological
      analysis and 26.4% by microbiological culture, with predominance in the female
      sex. Epigastralgia is the main reason for consultation associated with H. pylori
      infection. CONCLUSION: we found an association between the reason for
      consultation, female sex, microbiological culture and histological presence of H.
      pylori. Age was associated with established endoscopic diagnosis. The culture
      presented a high specificity (84.2%) and a low sensitivity (38.2%), compared to
      the histopathological finding.

PMID- 30118461
TI  - [Frequency of fecal incontinence and its impact on the quality of life of the
      hospitalized geriatric patient].
AB  - OBJECTIVE: To determine the frequency of fecal incontinence and the impact on the
      quality of life of hospitalized geriatric patients in a sample from a level two
      hospital in Monterrey, Nuevo Leon, Mexico. MATERIALS AND METHODS: Hospitalized
      patients over 60 years of age or their caregivers were questioned about the
      presence of fecal incontinence. Those who responded affirmatively and could
      respond were given the following questionnaires and scales: Mini-Mental, Rockwood
      quality of life for fecal incontinence and Wexner scale modified for severity of
      incontinence; in addition to clinical data. The frequency was calculated based on
      a sample and associations were determined between degree of incontinence and
      quality of life. RESULTS: A total of 234 patients were questioned, of whom 135
      (57.69%) were women and 99 (42.31%) men. A total of 34 patients with fecal
      incontinence were documented, this represents a frequency of 14.53% (95% CI,
      10.28-19.71%) in this population. A positive correlation of the severity of
      incontinence was found with the lifestyle dimension (relation (r) = -0.61, p =
      0.04), shame (r = -0.70, p = 0.01), behavior (r = -0.73, p = 0.001) and the
      average of the four dimensions (r = -0.67, p = 0.02) but not with the depression
      dimension of the quality of life questionnaire in fecal incontinence. CONCLUSION:
      When compared with other national and international studies, the frequency of
      fecal incontinence found was lower than that documented in other series. The
      quality of life of hospitalized elderly patients with fecal incontinence in this
      sample was diminished and its impact on quality of life correlated with the
      severity of fecal incontinence.

PMID- 30118462
TI  - [Safety of gastroenterologist-directed propofol administration for endoscopic
      procedures: 10-year experience in a private clinic in Lima, Peru].
AB  - OBJECTIVE: To evaluate safety of propofol combined with Meperidine and Midazolam
      in colonoscopies, upper endoscopies (EGD) and Endoscopic Ultrasound (EUS)
      administered by a nurse supervised by a trained gastroenterologist. To compare
      the required doses of propofol among older and younger than 75 years old.
      MATERIALS AND METHODS: Retrospective descriptive study including patients 18
      years of age and older who received propofol for EGD, colonoscopy (or EGD +
      colonoscopy) and EUS. The patients were given a baseline dose of Meperidine (25
      mg) and Midazolam (1-3 mg) intravenously (IV). After 2-3 minutes, they received
      an IV bolus of propofol between 10-30 mg. Repeat boluses of 10-20 mg were
      administered at intervals no lesser than 60 seconds during the procedure, as
      needed according to patient's tolerance to the procedure. RESULTS: Between
      September 2006 and September 2016, 9,704 procedures were performed, of which
      1,598 were EGD, 3,065 colonoscopies, 2,492 EGD + colonoscopies and 57 EUS. There
      were 3,912 women (59.1%), and the average age was 57.1 +/- 14.6 years. Eight
      hundred eighty (12.5%) were older than 75 years. The average dose of propofol for
      all the procedures was 83.2 +/- 48.1 mg, for EGD and colonoscopy was 59.7 +/-
      36.2 mg and 77.2 +/- 41 mg respectively. The average dose used in patients >75
      years for EGD was 47.5 +/- 37.8 mg, for colonoscopies 58.3 +/- 33.4 mg and for
      EGD + colonoscopies was 78.7 +/- 42.7 mg compared to patients <75 years in whom
      the average dose for EGD was 61.1 +/- 35.8 mg (p<0.05), in colonoscopies was 80.5
      +/- 41.3 mg (p<0.05) and in EGD + colonoscopies 105.9 +/- 50.2 mg (p<0.05). There
      were no sedation-related complications. CONCLUSIONS: Propofol combined with
      meperidine and midazolam in endoscopic procedures directed by a trained
      gastroenterologist is safe. Elderly patients (>75 years old) required
      significantly less doses of propofol for EGD, colonoscopy, EGD/colonoscopy and
      EUS.

PMID- 30118463
TI  - HAP score as prognostic factor of hepatocellular carcinoma treated with
      transarterial chemoembolization in a Latin American center.
AB  - INTRODUCTION: Hepatocellular carcinoma (HCC) in cirrhosis is diagnosed, most of
      times, when it is not susceptible to curative treatment. Transarterial
      chemoembolization (TACE) is a palliative therapeutic option with heterogeneous
      results. The HAP score stratifies patients who will benefit from the first TACE.
      OBJECTIVE: To evaluate if the HAP score is a prognostic factor of HCC treated
      with TACE. MATERIALS AND METHODS: Retrospective cohort study in cirrhotic
      patients with HCC and first TACE at the Edgardo Rebagliati Martins National
      Hospital, Lima-Peru, from June 2011 to June 20139. The HAP score was applied,
      mortality and survival were observed with a follow-up of 36 months. RESULTS: We
      included 54 patients with age of 67.7+/-9.9 years, 59.3% Child-Pugh A and 40.7%
      Child-Pugh B, MELD score of 11+/-2.7; 51.9 and 40.7% were BCLC A and B,
      respectively; 66.7% had a single tumor and 70.4% had a predominant tumor <5cm.
      The HAP score classified 8, 14, 26 and 6 patients as HAP A, B, C and D,
      respectively. The overall survival was 19.5+/-11.2 months and 32.8+/-6.5 months
      for HAP A, 24.9+/-14.8 months for HAP B, 13.9+/-5.2 months for HAP C and 14+/-6.6
      months for HAP D. There were no deaths at 12 months in HAP A. At 24 months,
      mortality for HAP C and D was 100%. At 36 months, the survival rate for HAP A and
      B was 75 and 42.9%, respectively. CONCLUSIONS: The HAP score is a useful tool to
      guide the management decisions of cirrhotic patients with HCC requiring TACE due
      to its value in predicting mortality and survival.

PMID- 30118464
TI  - Management of pancreatitis and pancreatic: fluid collections.
AB  - Acute pancreatitis is a constant management challenge, especially with
      peripancreatic collection that are one of the most common complications; after
      the first surgical attempts that had high mortality, there had to be a new
      approach based in decades of acquired knowledge in physiopathology added to the
      development of endoscopic intervention techniques and the evolution of endoscopic
      devices help to establish less invasive and conservative management. This review
      allows us to know the last advances in the management of acute pancreatitis,
      pancreatic pseudocyst and walled off necrosis, determined the right time for the
      management to become more invasive, even considering surgery at a final stage. It
      also reviews the different types of drainage of peripancreatic collections and
      the accessories currently in use.

PMID- 30118465
TI  - [Abernethy malformation: unusual cause of central cyanosis in pediatrics].
AB  - The congenital portosystemic shunt is an uncommon disease with severe
      complications if not treated. This rare cause of hypoxemia was first described by
      John Abernethy in 1973. There are two types: type I (termino-lateral shunt), in
      which there is total absence of the intrahepatic portal flow, and type II (latero
      lateral shunt), in which the portal flow is partially preserved. We present the
      case of a 6-year-old girl with chronic hypoxemia history since 4 and a half years
      of age, showing progressive dyspnea, who was referred to the Pediatric Pulmonary
      Division with the diagnosis of central cyanosis. An Echo-Doppler in the portal
      venous system was performed, reporting agenesis of the principal portal vein.
      This finding was corroborated by an angiography of the portal and mesenteric
      arteriovenous system. The study was completed with a portosplenography, which
      confirmed the diagnosis of type Ib Abernethy malformation. The type I Abernethy
      malformation is more common in females, shows up in different ways and is treated
      with liver transplantation. On the other hand, type II Abernethy malformation
      shows a variable portal circulation and has a better prognosis than type I.
      Dyspnea when exercising and central cyanosis should be considered to make a
      differential diagnosis of cardiorespiratory disease at a pediatric age.

PMID- 30118466
TI  - [Ampulloma treatment with Whipple surgery. First case report in the regional
      hospital of Tumbes].
AB  - To report the first case of Whipple surgery performed at the Regional Hospital of
      Tumbes for the treatment of ampullary adenocarcinoma with successful results. A
      case report of a patient with diagnosis of ampullary adenocarcinoma, in whom was
      performed the first Whipple surgery at the Regional Hospital of Tumbes, in
      October, 2014. The patient diagnosed with an obstructive jaundice syndrome due to
      ampullary adenocarcinoma underwent Whipple surgery. She performed the
      postoperative period with gradual improvement, she did not present with
      respiratory pathology, she not have fever, the patient tolerated the oral route,
      the jaundice decreased and she was discharged after 13 days. She presented low
      output pancreatic fistula (30 cc/day), which remitted at 3 weeks. The patient
      presented evident clinical improvement and satisfactory surgical results to date.
      Whipple surgery is the surgical technique of choice in the treatment of the
      ampullary adenocarcinoma and it is feasible to perform, in cases that is
      indicated, in bounderies hospitals if you have the trained personnel and
      necessary logistics.

PMID- 30118468
TI  - [Martius procedure in complex anorectal-vaginal fistula management: five-case
      report].
AB  - The repair of complex anorectal-vaginal fistulas represents an anatomic-surgical
      challenge for the surgeon, and the appropriate surgical procedure must be
      selected for each case. The procedure of Martius is described as the
      transposition of the bulbocavernosus muscle to repair the recto-vaginal fistula.
      Five cases of anorectal-vaginal fistulae were repaired by this procedure from
      2010 to 2014. The mean age was 38.2 years; three fistulas (60%) were of obstetric
      etiology, one induced by radiation and one of unknown etiology. The mean follow
      up was 25 months, with a 100% success rate. The Martius procedure is a good
      alternative for the surgical repair of complex anorectal-vaginal fistulas.

PMID- 30118467
TI  - [Colonic metastases from carcinoma of the lung, an unusual presentation. Case
      report and literature review].
AB  - The symptomatic metastasis of the colon from a pulmonary cancer is rare; however,
      the global incidence of pulmonary cancer is 12.9%. It is an infrequent site of
      metastasis, with a prevalence of less than 0.5% in patients with pulmonary
      cancer. One of the most common manifestation is intestinal obstruction. We
      present a case report of a patient with an acute lower intestinal bleeding from
      multiple metastasis lesion of the colon as the initial manifestation of a non
      small cell lung carcinoma.

PMID- 30118469
TI  - [Giant hepatic hemangioma, an uncommon presentation of a frequent disease].
AB  - Hepatic hemangiomas, also referred to as cavernous hemangiomas, are the most
      common benign mesenchymal hepatic tumors. They are often solitary, small lesions
      that have an excellent safety-prognosis and were commonly incidentally detected.
      Hepatic hemangiomas are frequently asymptomatic, although symptoms are more
      likely in those lesions larger than 5 cm also referred to as giant hemangiomas.
      We present a case of a pauci-asymptomatic 43 year-old woman with an uncommon
      16x16x27 cm giant hemangioma and perform a review of the literature.

PMID- 30118470
TI  - [Endoscopic-radiologic rendezvous for biliary obstruction management. Case report
      and literature review].
AB  - Biliary obstruction of different origin is a common clinical problem, with
      significant impact on the patients quality of life and poses a permanent risk of
      cholangitis. The management of these patients has evolved over time, makes
      collection of various technological developments and involve clinicians,
      surgeons, gastroenterologists, and interventional radiologists. Were port four
      cases of biliary obstruction that despite the significant demographic and
      clinical differences between them could be successfully managed approach in the
      biliary tract with the technique of radiological endoscopic Rendezvous.

PMID- 30118471
TI  - [Fatal bacteremia as a complication of hepatic abscess due to Achromobacter
      xylosoxidans: presentation as a complication in a patient with diabetes mellitus
      and liver cirrhosis].

PMID- 30118472
TI  - [Endoscopic treatment of Zenker's diverticulum in Latin America].

PMID- 30118474
TI  - How ecological feedbacks between human population and land cover influence
      sustainability.
AB  - It is estimated that the Earth's biocapacity is unable to meet current demands,
      which begs the question: is a sustainable future possible for both humans and the
      environment? The UN projects a human population of approximately 11 billion by
      the end of the 21st century; requiring additional agricultural land, greater
      demands for natural resources, and technological advancements. We model human
      population over the next century, emphasizing feedbacks between natural and
      agricultural resource availability and human demography. We argue that an
      intensive agriculture approach to feeding the growing population is ill
      conceived, without considering biodiversity and ecosystem services (e.g.,
      nutrient cycling, pollination, water purification, pest control). The
      productivity of agricultural land and human population dynamics are dependent on
      the area of natural land-generally, tipping at 5 billion ha of natural land
      (approximately 40% of the Earth's terrestrial area). Furthermore, our model shows
      that an imprudent proactive approach (i.e., focusing on agriculture and ignoring
      ecosystem services) limits the success of reactive measures (i.e., restoration)
      in the future, while the inability to react to changes and recover natural
      systems leads to human population decline.

PMID- 30118473
TI  - Exploring of the feature space of de novo developed post-transcriptional
      riboregulators.
AB  - Metabolic engineering increasingly depends upon RNA technology to customly rewire
      the metabolism to maximize production. To this end, pure riboregulators allow
      dynamic gene repression without the need of a potentially burdensome coexpressed
      protein like typical Hfq binding small RNAs and clustered regularly interspaced
      short palindromic repeats technology. Despite this clear advantage, no clear
      general design principles are available to de novo develop repressing
      riboregulators, limiting the availability and the reliable development of these
      type of riboregulators. Here, to overcome this lack of knowledge on the
      functionality of repressing riboregulators, translation inhibiting RNAs are
      developed from scratch. These de novo developed riboregulators explore features
      related to thermodynamical and structural factors previously attributed to
      translation initiation modulation. In total, 12 structural and thermodynamic
      features were defined of which six features were retained after removing
      correlations from an in silico generated riboregulator library. From this
      translation inhibiting RNA library, 18 riboregulators were selected using a
      experimental design and subsequently constructed and co-expressed with two target
      untranslated regions to link the translation inhibiting RNA features to
      functionality. The pure riboregulators in the design of experiments showed
      repression down to 6% of the original protein expression levels, which could only
      be partially explained by a ordinary least squares regression model. To allow
      reliable forward engineering, a partial least squares regression model was
      constructed and validated to link the properties of translation inhibiting RNA
      riboregulators to gene repression. In this model both structural and
      thermodynamic features were important for efficient gene repression by pure
      riboregulators. This approach enables a more reliable de novo forward engineering
      of effective pure riboregulators, which further expands the RNA toolbox for gene
      expression modulation.

PMID- 30118475
TI  - ggsashimi: Sashimi plot revised for browser- and annotation-independent splicing
      visualization.
AB  - We present ggsashimi, a command-line tool for the visualization of splicing
      events across multiple samples. Given a specified genomic region, ggsashimi
      creates sashimi plots for individual RNA-seq experiments as well as aggregated
      plots for groups of experiments, a feature unique to this software. Compared to
      the existing versions of programs generating sashimi plots, it uses popular
      bioinformatics file formats, it is annotation-independent, and allows the
      visualization of splicing events even for large genomic regions by scaling down
      the genomic segments between splice sites. ggsashimi is freely available at
      https://github.com/guigolab/ggsashimi. It is implemented in python, and
      internally generates R code for plotting.

PMID- 30118476
TI  - The role of curvature feedback in the energetics and dynamics of lamprey
      swimming: A closed-loop model.
AB  - Like other animals, lampreys have a central pattern generator (CPG) circuit that
      activates muscles for locomotion and also adjusts the activity to respond to
      sensory inputs from the environment. Such a feedback system is crucial for
      responding appropriately to unexpected perturbations, but it is also active
      during normal unperturbed steady swimming and influences the baseline swimming
      pattern. In this study, we investigate different functional forms of body
      curvature-based sensory feedback and evaluate their effects on steady swimming
      energetics and kinematics, since little is known experimentally about the
      functional form of curvature feedback. The distributed CPG is modeled as chains
      of coupled oscillators. Pairs of phase oscillators represent the left and right
      sides of segments along the lamprey body. These activate muscles that flex the
      body and move the lamprey through a fluid environment, which is simulated using a
      full Navier-Stokes model. The emergent curvature of the body then serves as an
      input to the CPG oscillators, closing the loop. We consider two forms of
      feedback, each consistent with experimental results on lamprey proprioceptive
      sensory receptors. The first, referred to as directional feedback, excites or
      inhibits the oscillators on the same side, depending on the sign of a chosen gain
      parameter, and has the opposite effect on oscillators on the opposite side. We
      find that directional feedback does not affect beat frequency, but does change
      the duration of muscle activity. The second feedback model, referred to as
      magnitude feedback, provides a symmetric excitatory or inhibitory effect to
      oscillators on both sides. This model tends to increase beat frequency and
      reduces the energetic cost to the lamprey when the gain is high and positive.
      With both types of feedback, the body curvature has a similar magnitude. Thus,
      these results indicate that the same magnitude of curvature-based feedback on the
      CPG with different functional forms can cause distinct differences in swimming
      performance.

PMID- 30118477
TI  - Unraveling the mechanism of the cadherin-catenin-actin catch bond.
AB  - The adherens junctions between epithelial cells involve a protein complex formed
      by E-cadherin, beta-catenin, alpha-catenin and F-actin. The stability of this
      complex was a puzzle for many years, since in vitro studies could reconstitute
      various stable subsets of the individual proteins, but never the entirety. The
      missing ingredient turned out to be mechanical tension: a recent experiment that
      applied physiological forces to the complex with an optical tweezer dramatically
      increased its lifetime, a phenomenon known as catch bonding. However, in the
      absence of a crystal structure for the full complex, the microscopic details of
      the catch bond mechanism remain mysterious. Building on structural clues that
      point to alpha-catenin as the force transducer, we present a quantitative
      theoretical model for how the catch bond arises, fully accounting for the
      experimental lifetime distributions. The underlying hypothesis is that force
      induces a rotational transition between two conformations of alpha-catenin,
      overcoming a significant energy barrier due to a network of salt bridges. This
      transition allosterically regulates the energies at the interface between alpha
      catenin and F-actin. The model allows us to predict these energetic changes, as
      well as highlighting the importance of the salt bridge rotational barrier. By
      stabilizing one of the alpha-catenin states, this barrier could play a role in
      how the complex responds to additional in vivo binding partners like vinculin.
      Since significant conformational energy barriers are a common feature of other
      adhesion systems that exhibit catch bonds, our model can be adapted into a
      general theoretical framework for integrating structure and function in a variety
      of force-regulated protein complexes.

PMID- 30118478
TI  - Sphingosine-1-phosphate signaling in Leishmania donovani infection in
      macrophages.
AB  - BACKGROUND: Sphingosine-1-phosphate (S1P) is a crucial regulator of a wide array
      of cellular processes, such as apoptosis, cell proliferation, migration, and
      differentiation, but its role in Leishmania donovani infection is unknown.
      METHODOLOGY/ PRINCIPAL FINDINGS: In the present study, we observed that L.
      donovani infection in THP-1 derived macrophages (TDM) leads to decrease in the
      expression of S1pr2 and S1pr3 at mRNA level. We further observed that Leishmania
      infection inhibits the phosphorylation of sphingosine kinase 1 (sphK1) in a time
      dependent manner. Exogenous S1P supplementation decreases L. donovani induced
      ERK1/2 phosphorylation and increases p38 phosphorylation in TDM, resulting in a
      decrease in the intracellular parasite burden in a dose-dependent manner. On the
      other hand, sphK inhibition by DMS increases ERK1/2 phosphorylation leading to
      increased IL-10 and parasite load. To gain further insight, cytokines expression
      were checked in S1P supplemented TDM and we observed increase in IL-12, while
      decrease IL-10 expression at mRNA and protein levels. In addition, treatment of
      antagonist of S1PR2 and S1PR3 such as JTE-013 and CAY10444 respectively enhanced
      Leishmania-induced ERK1/2 phosphorylation and parasite load. CONCLUSIONS: Our
      overall study not only reports the significant role of S1P signaling during L.
      donovani infection but also provides a novel platform for the development of new
      drugs against Leishmaniasis.

PMID- 30118479
TI  - The methyltransferase HEN1 is required in Nematostella vectensis for microRNA and
      piRNA stability as well as larval metamorphosis.
AB  - Small non-coding RNAs (sRNAs) such as microRNAs (miRNAs), small interfering RNAs
      (siRNAs) and piwi-interacting RNAs (piRNAs) regulate the levels of endogenous,
      viral and transposable element RNA in plants (excluding piRNAs) and animals.
      These pathways are explored mainly in bilaterian animals, such as vertebrates,
      arthropods and nematodes, where siRNAs and piRNAs, but not miRNAs bind their
      targets with a perfect match and mediate the cleavage of the target RNA.
      Methylation of the 3' ends of piRNAs and siRNAs by the methyltransferase HEN1
      protects these sRNAs from degradation. There is a noticeable selection in
      bilaterian animals against miRNA-mRNA perfect matching, as it leads to the
      degradation of miRNAs. Cnidarians (sea anemones, corals, hydroids and jellyfish),
      are separated from bilaterians by more than 600 million years. As opposed to
      bilaterians, cnidarian miRNAs frequently bind their targets with a nearly perfect
      match. Knowing that an ortholog of HEN1 is widely expressed in the sea anemone
      Nematostella vectensis, we tested in this work whether it mediates the
      stabilization of its sRNAs. We show that the knockdown of HEN1 in Nematostella
      results in a developmental arrest. Small RNA sequencing revealed that the levels
      of both miRNAs and piRNAs drop dramatically in the morphant animals. Moreover,
      knockdown experiments of Nematostella Dicer1 and PIWI2, homologs of major
      bilaterian biogenesis components of miRNAs and piRNAs, respectively, resulted in
      developmental arrest similar to HEN1 morphants. Our findings suggest that HEN1
      mediated methylation of sRNAs reflects the ancestral state, where miRNAs were
      also methylated. Thus, we provide the first evidence of a methylation mechanism
      that stabilizes miRNAs in animals, and highlight the importance of post
      transcriptional regulation in non-bilaterian animals.

PMID- 30118480
TI  - North American Culex pipiens and Culex quinquefasciatus are competent vectors for
      Usutu virus.
AB  - BACKGROUND: Usutu virus (USUV) is a member of the Japanese encephalitis virus
      (JEV) serocomplex in the Flaviviridae family. Emergence of USUV in Europe has led
      to disease burdens in birds and created increasing concern for the potential
      zoonotic transmission to humans. Whilst USUV has not been detected in the New
      World, the identification of competent vector species in North America is
      critical in the assessment of the likelihood of its dispersal and establishment
      of enzootic transmission cycles. The objective of this study was to determine
      vector competence of potential mosquito vectors in North America for USUV. Three
      medically important mosquito species were selected for testing because of their
      involvement in the transmission of West Nile virus and St. Louis encephalitis
      virus, two related JEV serocomplex flaviviruses in the New World.
      METHODOLOGY/PRINCIPAL FINDINGS: Oral challenge of Culex pipiens, Culex
      quinquefasciatus, and Aedes albopictus was performed to determine the
      susceptibility and vector competence of North American mosquitoes for USUV.
      Infection status was monitored by the isolation of virus from homogenized
      mosquito tissues. The disseminated form of infection was demonstrated by the
      detection of infectious virus in the head, wings, and legs of infected
      mosquitoes. The presence of viral RNA in saliva of infected Cx. pipiens and Cx.
      quinquefasciatus indicated that both species are competent for transmission of
      USUV. CONCLUSIONS/SIGNIFICANCE: Results indicate that members of the Cx. pipiens
      complex are susceptible to USUV and competent for its transmission potential in
      North America in the event of its introduction. In contrast, Ae. albopictus were
      highly refractory to USUV infection, suggesting that this species is unlikely to
      contribute to USUV transmission in North America.

PMID- 30118482
TI  - A novel recombinant human plasminogen activator: Efficient expression and
      hereditary stability in transgenic goats and in vitro thrombolytic bioactivity in
      the milk of transgenic goats.
AB  - BACKGROUND: Thromboses is a rapidly growing medical problem worldwide. Low-cost,
      high-scale production of thrombotic drugs is needed to meet the demand. The
      production of biomolecules in transgenic animals might help address this issue.
      To our knowledge, the expression of recombinant human plasminogen activator
      (rhPA) in goat mammary glands has never been reported before. METHODS: We
      constructed a mammary gland-specific expression vector, BLC14/rhPA, which encodes
      only the essential K2 fibrin-binding and P domains of wild-type tPA (deletion
      mutant of tPA lacking the F, E, and K1 domains), along with the goat beta
      lactoglobulin gene signal peptide-coding sequence. The mammary gland-specific
      expression vector BLC14/rhPA was transfected into goat fetal fibroblast cells by
      electroporation. After selection for 3 weeks by G418, stably transfected cell
      colonies were obtained. PCR analysis results indicated that 24 of the resistant
      clones were transgenic cell lines; of these, 8 lines were selected as the donor
      cells. The positive cells were starved for 72 h with DMEM/F12 medium containing
      0.5% FBS and were then used as do. Finally, 256 reconstructed oocytes were
      transferred into 26 recipients, and 7 of them became pregnant (pregnancy rate,
      26.9%). Two kids were obtained (BP21 and BP22). PCR analysis confirmed that both
      were transgenic goats. To analyze the heredity of the rhPA expressed in BP21 F0
      and F1 transgenic goats, the F0 transgenic goat BP21 was mated with a normal male
      goat to generate an F1 transgenic goat. Enucleated metaphase II (MII) oocytes and
      positive donor cells were used to reconstruct embryos, which were transplanted
      into the oviducts of the recipients. RESULTS: Western blot results showed a
      specific 39 kDa band. The rhPA expression level in transgenic goat whey was about
      78.32 MUg/mL by ELISA. Results of ELISA and the in vitro thrombolysis test (FAPA)
      showed that specific activity of the rhPA in the milk of F0 and F1 transgenic
      goats was 13.3 times higher than that of the reteplase reference material.
      CONCLUSION: Thus, we demonstrated that BLC14/rhPA was reasonably effective for
      expression in the mammary glands of transgenic goats, and was stably inherited by
      the offspring. This study provides the basis for the large-scale production of
      biological pharmaceuticals in transgenic animals. The expression of
      biopharmaceuticals by transgenic animals can be used for pharmacological research
      and bioactive analysis, and transgenic goats were demonstrated to be promising
      animals for the large-scale production of thrombolytic biopharmaceuticals.

PMID- 30118481
TI  - A RAD-sequencing approach to genome-wide marker discovery, genotyping, and
      phylogenetic inference in a diverse radiation of primates.
AB  - Until recently, most phylogenetic and population genetics studies of nonhuman
      primates have relied on mitochondrial DNA and/or a small number of nuclear DNA
      markers, which can limit our understanding of primate evolutionary and population
      history. Here, we describe a cost-effective reduced representation method (ddRAD
      seq) for identifying and genotyping large numbers of SNP loci for taxa from
      across the New World monkeys, a diverse radiation of primates that shared a
      common ancestor ~20-26 mya. We also estimate, for the first time, the
      phylogenetic relationships among 15 of the 22 currently-recognized genera of New
      World monkeys using ddRAD-seq SNP data using both maximum likelihood and quartet
      based coalescent methods. Our phylogenetic analyses robustly reconstructed three
      monophyletic clades corresponding to the three families of extant platyrrhines
      (Atelidae, Pitheciidae and Cebidae), with Pitheciidae as basal within the
      radiation. At the genus level, our results conformed well with previous
      phylogenetic studies and provide additional information relevant to the
      problematic position of the owl monkey (Aotus) within the family Cebidae,
      suggesting a need for further exploration of incomplete lineage sorting and other
      explanations for phylogenetic discordance, including introgression. Our study
      additionally provides one of the first applications of next-generation sequencing
      methods to the inference of phylogenetic history across an old, diverse radiation
      of mammals and highlights the broad promise and utility of ddRAD-seq data for
      molecular primatology.

PMID- 30118483
TI  - Association between progranulin serum levels and dietary intake.
AB  - INTRODUCTION: Progranulin (PGRN) is secreted by adipose tissue and has been
      linked to obesity, insulin resistance and type 2 diabetes mellitus. There is
      evidence that a high fat diet increases PGRN expression in rodent adipose tissue.
      In humans, the relationship between diet composition and concentration of PGRN is
      still unknown. OBJECTIVE: To investigate the association between dietary intake
      and serum PGRN levels. METHODS: This is an exploratory cross-sectional study
      including 85 subjects. Demographic, clinical, laboratory and anthropometric data
      were collected. Serum PGRN was determined by enzyme-linked immunosorbent assay
      after overnight fasting. Dietary intake was assessed by food frequency
      questionnaire validated for Brazilian southern population. Focused principal
      component analyses (FPCA) was used to verify the association of dietary
      components and food groups with PGRN levels. Sensitivity analyses were performed
      including only subjects with reporting according to the Goldberg and Black cut
      offs of energy intake-energy expenditure ratio between 0.76 and 1.24. RESULTS:
      The median PGRN was 51.96 (42.18 to 68.30) ng/mL. Analyzing all sample, the FPCA
      showed no association of serum PGRN with total energy, protein, carbohydrate, fat
      and its types, fiber intake and dietary glycemic index; but a significant and
      positive association between solid fats and PGRN levels (p<0.05). Including only
      subjects with reporting according cut-off of energy intake-energy expenditure
      ratio between 0.76 and 1.24, FCPA showed significant and positive association of
      serum PGRN with saturated fatty acids and solid fats intake (p<0.05). In this
      subgroup, PGRN correlated with saturated fatty acids (r = 0.341; p = 0.031).
      Solid fats intake was independently associated to serum PGRN (beta = 0.294; p =
      0.004) in multivariate model. CONCLUSION: The dietary intake of solid fats,
      mainly represented by saturated fatty acids, is associated to serum PGRN
      concentration in human subjects.

PMID- 30118484
TI  - E-cadherin bridges cell polarity and spindle orientation to ensure prostate
      epithelial integrity and prevent carcinogenesis in vivo.
AB  - Cell polarity and correct mitotic spindle positioning are essential for the
      maintenance of a proper prostate epithelial architecture, and disruption of the
      two biological features occurs at early stages in prostate tumorigenesis.
      However, whether and how these two epithelial attributes are connected in vivo is
      largely unknown. We herein report that conditional genetic deletion of E
      cadherin, a key component of adherens junctions, in a mouse model results in loss
      of prostate luminal cell polarity and randomization of spindle orientations.
      Critically, E-cadherin ablation causes prostatic hyperplasia which progresses to
      invasive adenocarcinoma. Mechanistically, E-cadherin and the spindle positioning
      determinant LGN interacts with the PDZ domain of cell polarity protein SCRIB and
      form a ternary protein complex to bridge cell polarity and cell division
      orientation. These findings provide a novel mechanism by which E-cadherin acts an
      anchor to maintain prostate epithelial integrity and to prevent carcinogenesis in
      vivo.

PMID- 30118485
TI  - Contraceptive use and unintended pregnancy among young women and men in Accra,
      Ghana.
AB  - The objective of this study was to determine factors associated with modern
      contraceptive use and unintended pregnancy among young women and men in Accra,
      Ghana. From September-December 2013, we conducted a cross-sectional survey with
      250 women and 100 men aged 18-24. We explored determinants of modern
      contraceptive use among males and females and unintended pregnancy among females.
      Descriptive statistics, chi-square tests, Fisher's exact tests, and multivariable
      logistic regression were used. Participants had an average of three lifetime
      sexual partners, and 91% had one current partner. Overall, 44% reported current
      modern contraceptive use. In multivariate modeling, modern contraceptive use was
      associated with higher education compared to primary (AORs 2.1-4.3); ever talking
      with someone about contraception (AOR 4.7); feeling unsupported by a healthcare
      provider for contraception (AOR 2.2); and not feeling at risk of unintended
      pregnancy (AOR 2.7). While >=70% of participants recognized most contraceptive
      methods, awareness of some methods was lacking. Nearly all respondents (91%) felt
      at least one modern method was unsafe. Nearly half of all females (45%) reported
      their last pregnancy was unintended, and 63% of females and 58% of males felt at
      risk for future unintended pregnancy. Women were more likely to experience
      unintended pregnancy if they had ever given birth (AOR 6.7), their sexual debut
      was 8-14 years versus 20-24 years (AOR 3.4), or they had 3-4 lifetime sexual
      partners versus 1-2 (AOR 2.4). Targeted interventions are needed to improve
      understanding of the safety of modern contraceptive methods, increase awareness
      of long-acting methods, and consequently increase modern contraceptive access and
      use.

PMID- 30118486
TI  - Nitroglycerin application and coronary arteriogenesis.
AB  - BACKGROUND: In the presence of a coronary occlusion, pre-existing small
      collateral vessels (arterioles) develop into much larger arteries (biological
      bypasses) that have the potential to allow a certain level of perfusion distal to
      the blockage. Termed arteriogenesis, this phenomenon proceeds via a complex
      combination of events, with nitric oxide (NO) playing an essential role. The aim
      of this study was to investigate the effects of supplemental administration of NO
      donors, i.e., short-acting nitroglycerin (NTG) or slow-release pelleted
      isosorbide dinitrate (ISDN), on collateral development in a repetitive coronary
      artery occlusion model in rats. METHODS: Coronary collateral growth was induced
      via a repetitive occlusion protocol (ROP) of the left anterior descending
      coronary artery (LAD) in rats. The primary endpoints were the histological
      evaluation of rat heart infarct size and ST-segment elevation (ECG-analysis) upon
      final permanent occlusion of the LAD (experimentally induced myocardial
      infarction). The effects of NTG or ISDN were also evaluated by administration
      during 5 days of ROP. We additionally investigated whether concomitant
      application of NTG can compensate for the anti-arteriogenic effect of
      acetylsalicylic acid (ASA). RESULTS: After 5 days of ROP, the mean infarct size
      and degree of ST-elevation were only slightly lower than those of the SHAM group;
      however, after 10 days of the protocol, the ROP group displayed significantly
      less severe infarct damage, indicating enhanced arteriogenesis. Intermittent NTG
      application greatly decreased the ST-elevation and infarct size. The ISDN also
      had a positive effect on arteriogenesis, but not to the same extent as the NTG.
      Administration of ASA increased the infarct severity; however, concomitant dosing
      with NTG somewhat attenuated this effect. CONCLUSION: Intermittent treatment with
      the short-acting NTG decreased the size of an experimentally induced myocardial
      infarct by promoting coronary collateral development. These new insights are of
      great relevance for future clinical strategies for the treatment of occlusive
      vascular diseases.

PMID- 30118487
TI  - BtsCI and BseGI display sequence preference in the nucleotides flanking the
      recognition sequence.
AB  - Restriction enzymes are the bread and butter of Molecular Biology. Nonetheless,
      how restriction enzymes recognize and cleave their target is not always clear.
      When developing a method for the enzymatic production of oligonucleotides, we
      noticed that type II endonucleases BtsCI and BseGI, which recognize the sequence
      GGATGNN^, perform incomplete digestions of DNA hairpins, with the top strand nick
      not always occurring correctly. We tested the cutting of synthetic hairpins
      containing all possible combinations of dinucleotides following the recognition
      site and our results show that all sequences containing one adenine following
      GGATG were digested more efficiently. We further show that the same sequence
      preference is also observable in double stranded DNA at higher Mg2+
      concentrations and even in optimal conditions. Kinetic results show that BtsCI
      has a noteworthy difference in the first-rate constants between different
      sequences and between the two catalytic domains. An increase in Mg2+ resulted in
      a drastic decrease in the catalytic activity of the top (sense) strand that
      wasn't always accompanied by a nick in the bottom strand (antisense).

PMID- 30118488
TI  - A Bayesian measure of association that utilizes the underlying distributions of
      noise and information.
AB  - We propose a new approach, Bayesian Probability of Association (BPA) which takes
      into account the probability distributions of information and noise in the
      variables and uses Bayesian statistics to predict associations better than
      existing approaches. Our approach overcomes the limitations of linearity of the
      relationship and normality of the data, assumed by the Pearson correlation
      coefficient. It is different from the current measures of association because
      considering information separately from noise helps identify the association in
      information more accurately, makes the approach less sensitive to noise and also
      helps identify causal directions. We tested the approach on 15 datasets with no
      underlying association and on 75 datasets with known causal relationships and
      compared the results with other measures of association. No false associations
      were detected and true associations were predicted in more than 90% cases whereas
      the Pearson correlation coefficient and mutual information content predicted
      associations for less than half of the datasets.

PMID- 30118489
TI  - Social isolation, cognitive reserve, and cognition in healthy older people.
AB  - There is evidence to suggest that social isolation is associated with poor
      cognitive health, although findings are contradictory. One reason for
      inconsistency in reported findings may be a lack of consideration of underlying
      mechanisms that could influence this relationship. Cognitive reserve is a
      theoretical concept that may account for the role of social isolation and its
      association with cognitive outcomes in later life. Therefore, we aimed to examine
      the relationship between social isolation and cognition in later life, and to
      consider the role of cognitive reserve in this relationship. Baseline and two
      year follow-up data from the Cognitive Function and Ageing Study-Wales (CFAS
      Wales) were analysed. Social isolation was assessed using the Lubben Social
      Network Scale-6 (LSNS-6), cognitive function was assessed using the Cambridge
      Cognitive Examination (CAMCOG), and cognitive reserve was assessed using a proxy
      measure of education, occupational complexity, and cognitive activity. Linear
      regression modelling was used to assess the relationship between social isolation
      and cognition. To assess the role of cognitive reserve in this relationship,
      moderation analysis was used to test for interaction effects. After controlling
      for age, gender, education, and physically limiting health conditions, social
      isolation was associated with cognitive function at baseline and two year follow
      up. Cognitive reserve moderated this association longitudinally. Findings suggest
      that maintaining a socially active lifestyle in later life may enhance cognitive
      reserve and benefit cognitive function. This has important implications for
      interventions that may target social isolation to improve cognitive function.

PMID- 30118490
TI  - Spatiotemporal analysis of canine rabies in El Salvador: Violence and poverty as
      social factors of canine rabies.
AB  - BACKGROUND: The incidence of canine rabies cases in El Salvador has decreased in
      the last decade since the establishment of intense control programs, such as
      massive vaccination campaigns implemented by the Ministry of Health.
      Socioeconomic crises in recent years have limited the access to certain areas
      across the country and have impacted surveillance and prevention campaigns, which
      places the country at risk for a resurgence of canine rabies.We aimedto describe
      the spatiotemporal patterns of canine rabies and its association with critical
      social factors in El Salvador from 2005 to 2014. METHOD: We included 459 cases of
      canine rabies. Several socioeconomic, demographic, and surveillance variables
      were modeled using a Poisson regression to evaluate their associations with the
      incidence of canine rabies. Spatial scan statistics were adjusted or unadjusted
      with covariates and applied to identify statistically significant clusters of
      canine rabies. Finally, a canine rabies risk map was created. RESULTS: A positive
      association and higher risk of canine rabies were found for low poverty zones,
      where it is suspected that urban slums contribute to ongoing rabies transmission
      (RR = 7.74). Violence had a negative association with rabies (RR = 0.663), which
      is likely due to reporting bias. Significant clusters were identified in all five
      epidemiological regions, and the Eastern region had the highest risk (RR =
      50.62). The influences of the selected variables in cluster detection were
      confirmed by the adjusted analysis. Higher-risk townships were distributed from
      the Western to the Eastern regions of the country. CONCLUSION: Social factors are
      determinants of rabies in El Salvador and play a major role in national spatial
      patterns of the disease. There are high-risk areas for canine rabies across the
      country, and there were two persistent rabies foci during the study period.
      Examining the role of social factors can provide better insight into rabies in
      vulnerable countries, and socioeconomic factors can be key elements in developing
      better policies and interventions for rabies control.

PMID- 30118491
TI  - Energy metabolism and partition of lactating Zebu and crossbred Zebu cows in
      different planes of nutrition.
AB  - The aim of this study was to determine the energy metabolism and partition of
      lactating Gyr and F1 Holstein x Gyr (F1 HxG) cows in different planes of
      nutrition. Six F1 HxG and six Gyr cows with 130 days in milking (DIM) fed corn
      silage and concentrate were evaluated. The experiment consisted of four periods
      with different levels of feeding: 1st ad libitum dry matter intake (DMI) and the
      others with 5, 10 and 20% restricted DMI, related to the first one. An apparent
      digestibility assay was performed before measurements in the respiration chamber.
      Total feces were collected for three days. The cows were confined for 24h in the
      chamber in each period to determine methane and heat production (HP). F1 HxG had
      higher gross energy intake (GEI), metabolisable energy intake (MEI) and
      digestible energy intake (DEI). GE lost in feces was higher in F1 HxG (23.7% GEI)
      than in Gyr (20.5%) cows. Energy lost as methane and urine was similar between
      the groups. The metabolisability (q) was 0.67, and the efficiency of converting
      ME to NE (k) was 0.56. There was no difference in the energy requirements for
      maintenance between breeds (426.6 MJ/kg BW0,75 average value). The energy
      requirements for lactation were higher in F1 HxG animals due to the higher volume
      of milk produced, since there was no difference in energy requirements for
      production of one kg of milk.

PMID- 30118492
TI  - Approximate sparse spectral clustering based on local information maintenance for
      hyperspectral image classification.
AB  - Sparse spectral clustering (SSC) has become one of the most popular clustering
      approaches in recent years. However, its high computational complexity prevents
      its application to large-scale datasets such as hyperspectral images (HSIs). In
      this paper, we propose two efficient approximate sparse spectral clustering
      methods for HSIs clustering in which clustering performance is improved by
      utilizing local information among the data. Firstly, we construct a smaller
      representative dataset on which sparse spectral clustering is performed. Then the
      labels of ground object are extending to whole dataset based on the local
      information according to two extending strategies. The first one is that the
      local interpolation is utilized to improve the extension of the clustering
      result. The other one is that the label extension is turned to a problem of
      subspace embedding, and is fulfilled by locally linear embedding (LLE). Several
      experiments on HSIs demonstrated that the proposed algorithms are effective for
      HSIs clustering.

PMID- 30118493
TI  - Shaking-B misexpression increases the formation of gap junctions but not chemical
      synapses between auditory sensory neurons and the giant fiber of Drosophila
      melanogaster.
AB  - The synapse between auditory Johnston's Organ neurons (JONs) and the giant fiber
      (GF) of Drosophila is structurally mixed, being composed of cholinergic chemical
      synapses and Neurobiotin- (NB) permeable gap junctions, which consist of the
      innexin Shaking-B (ShakB). Previous observations showed that misexpression of one
      ShakB isoform, ShakB(N+16), in a subset of JONs that do not normally form gap
      junctions results in their de novo dye coupling to the GF. Misexpression of the
      transcription factor Engrailed (En) in these neurons also has this effect, and in
      addition causes the formation of new chemical synapses. These results, along with
      earlier studies suggesting that gap junctions are required for the development of
      some chemical synapses, led to the hypothesis that ShakB would, like En, have an
      instructive effect on the distribution of mixed chemical/electrical contacts. To
      test this, we first confirmed quantitatively that ShakB(N+16) misexpression
      increased the dye-coupling of JONs with the GF, indicating the formation of
      ectopic gap junctions. Conversely, expression of the 'incorrect' isoform,
      ShakB(N), abolished dye coupling. Immunocytochemistry of the ShakB protein showed
      that ShakB(N+16) increased gap junctional plaques in JON axons but ShakB(N) did
      not. To test our hypothesis, fluorescently-labeled presynaptic active zone
      protein (Brp) was expressed in JONs and the changes in its distribution on the GF
      dendrites was assayed with confocal microscopy in animals with misexpression of
      ShakB(N+16), ShakB(N) or, as a positive control, En. Using different methods of
      image analysis, we confirmed our previous result that En misexpression increased
      the chemical synapses with the GF and the amount of GF medial dendrite branching.
      However, contrary to our hypothesis, misexpression of ShakB did not increase
      these parameters. Immunostaining showed no association between presynaptic active
      zones and the new ShakB plaques, further evidence against the hypothesis. We
      conclude that both subsets of JON form chemical synapses onto the GF dendrites
      but only one population forms gap junctions, comprised of ShakB(N+16).
      Misexpression of this isoform in all JONs does not instruct the formation of new
      mixed chemical/electrical synapses, but results in the insertion of new gap
      junctions, presumably at the sites of existing chemical synaptic contacts with
      the GF.

PMID- 30118494
TI  - Population genomics of Culiseta melanura, the principal vector of Eastern equine
      encephalitis virus in the United States.
AB  - BACKGROUND: Eastern Equine Encephalitis (EEE) (Togaviridae, Alphavirus) is a
      highly pathogenic mosquito-borne arbovirus that circulates in an enzootic cycle
      involving Culiseta melanura mosquitoes and wild Passeriformes birds in freshwater
      swamp habitats. Recently, the northeastern United States has experienced an
      intensification of virus activity with increased human involvement and northward
      expansion into new regions. In addition to its principal role in enzootic
      transmission of EEE virus among avian hosts, recent studies on the blood-feeding
      behavior of Cs. melanura throughout its geographic range suggest that this
      mosquito may also be involved in epizootic / epidemic transmission to equines and
      humans in certain locales. Variations in blood feeding behavior may be a function
      of host availability, environmental factors, and/or underlying genetic
      differences among regional populations. Despite the importance of Cs. melanura in
      transmission and maintenance of EEE virus, the genetics of this species remains
      largely unexplored. METHODOLOGY AND PRINCIPLE FINDINGS: To investigate the
      occurrence of genetic variation in Cs. melanura, the genome of this mosquito
      vector was sequenced resulting in a draft genome assembly of 1.28 gigabases with
      a contig N50 of 93.36 kilobases. Populations of Cs. melanura from 10 EEE virus
      foci in the eastern North America were genotyped with double-digest RAD-seq.
      Following alignment of reads to the reference genome, variant calling, and
      filtering, 40,384 SNPs were retained for downstream analyses. Subsequent analyses
      revealed genetic differentiation between northern and southern populations of
      this mosquito species. Moreover, limited fine-scale population structure was
      detected throughout northeastern North America, suggesting local differentiation
      of populations but also a history of ancestral polymorphism or contemporary gene
      flow. Additionally, a genetically distinct cluster was identified predominantly
      at two northern sites. CONCLUSION AND SIGNIFICANCE: This study elucidates the
      first evidence of fine-scale population structure in Cs. melanura throughout its
      eastern range and detects evidence of gene flow between populations in
      northeastern North America. This investigation provides the groundwork for
      examining the consequences of genetic variations in the populations of this
      mosquito species that could influence vector-host interactions and the risk of
      human and equine infection with EEE virus.

PMID- 30118495
TI  - Prevalence and correlates of hazardous alcohol consumption and binge drinking
      among men who have sex with men (MSM) in San Francisco.
AB  - OBJECTIVES: To describe heavy alcohol use patterns and correlates in a diverse
      sample of MSM. METHODS: We used respondent-driven sampling (RDS) to enroll 252
      alcohol-using MSM in San Francisco from March 2015-July 2017. We examined heavy
      alcohol use patterns and conducted RDS-adjusted multivariable analyses to
      characterize correlates of hazardous alcohol consumption and binge drinking.
      RESULTS: RDS-adjusted prevalence of weekly and at least weekly binge drinking was
      24.9% and 19.3%, respectively. Hazardous consumption was common; prevalence of
      mid- and high-levels of hazardous drinking was 11.4% and 29.9%, respectively. In
      multivariable analyses, identifying as Hispanic/Latino or mixed/other race; being
      moderately or extremely interested in reducing alcohol use; ever receiving
      alcohol treatment; using ecstasy; reporting syphilis diagnosis; and having more
      than 5 male partners were independently associated with hazardous alcohol
      consumption. Less hazardous consumption was associated with having a bachelor's
      degree or completing post-graduate studies; and not being in a relationship.
      Reporting chlamydia infection; being somewhat, moderately or extremely interested
      in reducing alcohol use; and having multiple male sex partners were associated
      with higher odds of at least weekly binge drinking. Lower odds of binge drinking
      were associated with completing post-graduate studies. Moreover, for the outcomes
      of hazardous alcohol consumption and binge-drinking, we observed significant
      interaction effects between race/ethnicity and interest in reducing alcohol, past
      receipt of alcohol treatment, use of ecstasy, syphilis diagnosis, and number of
      male partners. CONCLUSION: Among alcohol-using MSM in San Francisco, heavy
      drinking patterns were common and independently associated with greater number of
      male sexual partners and sexually transmitted infections (STI). Moreover,
      significant racial/ethnic and socioeconomic disparities related to heavy alcohol
      use were observed and race/ethnicity modified the effect of the risk factors
      associated with these outcomes. These findings underscore the need to develop
      more MSM-specific interventions that jointly address heavy alcohol use and
      HIV/STI risk, as well as culturally-tailored and targeted strategies to alleviate
      health disparities.

PMID- 30118497
TI  - Spatiotemporal prediction of infectious diseases using structured Gaussian
      processes with application to Crimean-Congo hemorrhagic fever.
AB  - BACKGROUND: Infectious diseases are one of the primary healthcare problems
      worldwide, leading to millions of deaths annually. To develop effective control
      and prevention strategies, we need reliable computational tools to understand
      disease dynamics and to predict future cases. These computational tools can be
      used by policy makers to make more informed decisions. METHODOLOGY/PRINCIPAL
      FINDINGS: In this study, we developed a computational framework based on Gaussian
      processes to perform spatiotemporal prediction of infectious diseases and
      exploited the special structure of similarity matrices in our formulation to
      obtain a very efficient implementation. We then tested our framework on the
      problem of modeling Crimean-Congo hemorrhagic fever cases between years 2004 and
      2015 in Turkey. CONCLUSIONS/SIGNIFICANCE: We showed that our Gaussian process
      formulation obtained better results than two frequently used standard machine
      learning algorithms (i.e., random forests and boosted regression trees) under
      temporal, spatial, and spatiotemporal prediction scenarios. These results showed
      that our framework has the potential to make an important contribution to public
      health policy makers.

PMID- 30118496
TI  - Differential changes to D1 and D2 medium spiny neurons in the 12-month-old Q175+/
      mouse model of Huntington's Disease.
AB  - Huntington's Disease (HD) is an autosomal dominant, progressive neurodegenerative
      disorder caused by deleterious expansion of CAG repeats in the Huntingtin gene
      and production of neurotoxic mutant Huntingtin protein (mHTT). The key
      pathological feature of HD is a profound degeneration of the striatum and a loss
      of cortical volume. The initial loss of indirect pathway (D2) medium spiny neuron
      (MSN) projections in early stages of HD, followed by a loss of direct pathway
      (D1) projections in advanced stages has important implications for the trajectory
      of motor and cognitive dysfunction in HD, but is not yet understood. Mouse models
      of HD have yielded important information on the effects and mechanisms of mHTT
      toxicity; however, whether these models recapitulate differential vulnerability
      of D1 vs. D2 MSNs is unknown. Here, we employed 12-month-old Q175+/- x D2-eGFP
      mice to examine the detailed structural and functional properties of D1 vs. D2
      MSNs. While both D1 and D2 MSNs exhibited increased input resistance, depolarized
      resting membrane potentials and action potential threshold, only D1 MSNs showed
      reduced rheobase, action potential amplitude and frequency of spontaneous
      excitatory postsynaptic currents. Furthermore, D1 but not D2 MSNs showed marked
      proliferative changes to their dendritic arbors and reductions in spine density.
      Immunohistochemical assessment showed no loss of glutamatergic afferent inputs
      from cortical and subcortical sources onto identified D1 and D2 MSNs.
      Computational models constrained by empirical data predict that the increased
      dendritic complexity in Q175+/- D1 MSNs likely leads to greater dendritic
      filtering and attenuation of signals propagating to the soma from the dendrites.
      Together these findings reveal that, by twelve months, D1 and D2 MSNs exhibit
      distinctive responses to the presence of mHTT in this important mouse model of
      HD. This further highlights the need to incorporate findings from D1 and D2 MSNs
      independently in the context of HD models.

PMID- 30118498
TI  - Inducible nitric oxide synthase 2 promoter polymorphism and malaria disease
      severity in children in Southern Ghana.
AB  - OBJECTIVE: We assessed the association of mutant allele frequencies of nitric
      oxide synthase 2 (NOS2) gene at two SNPs (-954 and -1173) with malaria disease
      severity in children from a malaria endemic area in Southern Ghana. METHOD: Using
      children recruited at the hospital, assigned into clinical subgroups of
      uncomplicated and severe malaria and matching with their "healthy control"
      counterparts, we designed a case control study. Genomic DNA was extracted and
      genotyping using Restriction Fragment Polymorphism was done. RESULT: A total of
      123 malaria cases (91 uncomplicated, 32 severe) and 100 controls were sampled.
      Their corresponding mean Hbs were 9.6, 9.3 and 11.2g/dl and geometric mean
      parasite densities of 32097, 193252 and 0 parasites/ml respectively. Variant
      allele frequencies varied from 0.09 through 0.03 to 0.12 for G-954C and 0.06
      through 0.03 to 0.07 for C-1173T in the uncomplicated, severe and healthy control
      groups respectively. There was a strong linkage disequilibrium between the two
      alleles (p<0.001). For the -954 position, the odds of developing severe malaria
      was found to be 2.5 times lower with the carriage of a C allele compared to those
      without severe malaria (chi2; p< 0.05) though this isn't the case with -1173.
      CONCLUSION: The carriage of a mutant allele in the -954 NOS2 gene may have a
      protective effect on malaria among Southern Ghanaian children.

PMID- 30118499
TI  - Molecular subtypes of colorectal cancer in pre-clinical models show differential
      response to targeted therapies: Treatment implications beyond KRAS mutations.
AB  - Molecular subtypes of colorectal tumors are associated with prognosis and
      prediction for treatment benefit from chemotherapy. The purpose of this study was
      two-fold: 1) to determine the association of colorectal (CRC) molecular subtypes
      with response to targeted therapies in pre-clinical models and 2) to identify
      treatments for CRC stem-like subtype because these tumors are associated with a
      very poor patient prognosis. Eleven CRC cell lines were classified into molecular
      subtypes and tested for their response to pan-ERBB, MEK, and ERK inhibitors as
      single agents and in combination. All six inflammatory or TA cell lines were
      exquisitely sensitive to the combination of MEK and neratinib whereas all five
      stem-like cell lines were resistant. Growth inhibition in sensitive cell lines
      was greater with the combination than with either drug alone even in cell lines
      with KRAS mutations. The combination inhibited pERK in inflammatory cell lines
      but not in four out of five stem-like cell lines. MEK162 plus neratinib were
      synergistic in cell culture and xenograft models in inflammatory cell lines. The
      ERK inhibitor, SCH772984, down-regulated pERK, decreased cell viability, and was
      synergistic with neratinib in both inflammatory and stem-like subtypes. These
      results suggest that inhibition of pERK is a critical node in decreasing cell
      viability of stem-like CRC tumors. Our results also suggest that CRC molecular
      subtypes may yield predictive information and may help to identify patients who
      may respond to targeted inhibitors.

PMID- 30118500
TI  - Trans-chalcone increases p53 activity via DNAJB1/HSP40 induction and CRM1
      inhibition.
AB  - Naturally-occurring chalcones and synthetic chalcone analogues have been
      demonstrated to have many biological effects, including anti-inflammatory, anti
      malarial, anti-fungal, and anti-oxidant/anti-cancerous activities. Compared to
      other chalcones, trans-chalcone exhibits superior inhibitory activity in cancer
      cell growth as shown via in vitro assays, and exerts anti-cancerous effects via
      the activation of the p53 tumor suppressor protein. Thus, characterization of the
      specific mechanisms, by which trans-chalcone activates p53, can aid development
      of new chemotherapeutic drugs that can be used individually or synergistically
      with other drugs. In this report, we found that trans-chalcone modulates many p53
      target genes, HSP40 being the most induced gene in the RNA-Seq data using trans
      chalcone-treated cells. CRM1 is also inhibited by trans-chalcone, resulting in
      the accumulation of p53 and other tumor suppressor proteins in the nucleus.
      Similar effects were seen using trans-chalcone derivatives. Overall, trans
      chalcone could provide a strong foundation for the development of chalcone-based
      anti-cancer drugs.

PMID- 30118501
TI  - Evolutionary dynamics of cryptocurrency transaction networks: An empirical study.
AB  - Cryptocurrency is a well-developed blockchain technology application that is
      currently a heated topic throughout the world. The public availability of
      transaction histories offers an opportunity to analyze and compare different
      cryptocurrencies. In this paper, we present a dynamic network analysis of three
      representative blockchain-based cryptocurrencies: Bitcoin, Ethereum, and
      Namecoin. By analyzing the accumulated network growth, we find that, unlike most
      other networks, these cryptocurrency networks do not always densify over time,
      and they are changing all the time with relatively low node and edge repetition
      ratios. Therefore, we then construct separate networks on a monthly basis, trace
      the changes of typical network characteristics (including degree distribution,
      degree assortativity, clustering coefficient, and the largest connected
      component) over time, and compare the three. We find that the degree distribution
      of these monthly transaction networks cannot be well fitted by the famous power
      law distribution, at the same time, different currency still has different
      network properties, e.g., both Bitcoin and Ethereum networks are heavy-tailed
      with disassortative mixing, however, only the former can be treated as a small
      world. These network properties reflect the evolutionary characteristics and
      competitive power of these three cryptocurrencies and provide a foundation for
      future research.

PMID- 30118502
TI  - Effect of heat and pectinase maceration on phenolic compounds and physicochemical
      quality of Strychnos cocculoides juice.
AB  - Strychnos cocculoides fruit is an important food source for rural populations in
      Zimbabwe in times of scarcity. Its thick pulp tightly adheres to its seeds,
      causing pulp extraction constraints and waste during processing, leading to
      underutilisation. Therefore, pectinase maceration combined with heat treatments
      was studied to improve juice yield and juice quality. Metabolite profiling
      according to the heat map, FancyTile chromatic scale approach and phenolic
      compound content were used to compare the identified compounds. Prior to
      treatments, 16 known phenolic compounds, predominantly belonging to the phenolic
      acids, flavonoids and iridoid glucoside classes, were tentatively characterized
      for the first time in S. cocculoides using High Resolution Mass Spectrometry and
      LC/MS/MS. Overall, results showed that enzymatic treatments increased pulp yield
      (by 26%), physicochemical quality (38% increase in juice clarity), content of
      phenolic compounds (predominantly kaempferol, quercetin, caffeic acid,
      protocatechuic acid, iridoids) and antioxidant activity.The improved extraction
      of S. cocculoides pulp increases juice yield as well as juice quality by
      supplying larger amounts of phenolic compounds that have potential health
      benefits and act as dietary sources of antioxidants for the prevention of
      diseases caused by oxidative stress.

PMID- 30118503
TI  - Adhesion awareness in 2016: An update of the national survey of surgeons.
AB  - BACKGROUND AND AIMS: Adhesions, that form in 60-80% of all abdominal operations,
      can cause complications such as chronic abdominal pain, small-bowel obstruction,
      female infertility, and the need for adhesiolysis in future surgeries. Our 2010
      Adhesion Awareness survey demonstrated that despite the huge clinical impact of
      adhesions; adhesion-related complications were seldom mentioned in the informed
      consent. Six years later, a follow-up survey was conducted to assess the progress
      on awareness on adhesion-related complications in the Netherlands. MATERIAL AND
      METHODS: The 2010 Adhesion Awareness survey was repeated after a literature
      update. The knowledge regarding adhesions; the use of anti-adhesive agents and
      involvement in the informed consent process were assessed. Surgeons and surgical
      trainees were contacted by e-mail. The data was analysed using a Chi-square or
      Mann-Whitney U test and corrected for multiple testing. RESULTS: The response
      rate was 32.6%, similar to the survey in 2010 (34.4%). 88.1% agreed with the
      clinical relevance of adhesions, comparable to 2010 (89.8%). The score on the
      knowledge test was 38.8% (2010: 37.2%). Involvement of adhesion-related
      complications in the informed consent process increased, although 32.5% almost
      never mentions adhesions. In 2016, 42.4% reported a correct occurrence of bowel
      lesions during adhesiolysis, higher than in 2010 (P<0.001). CONCLUSIONS: The
      adhesion awareness did not increase in six years, despite the efforts made.
      However, an increased awareness regarding adhesiolysis related complications was
      detected. Improvement of knowledge and behavior is essential to narrowing the gap
      between the impact of adhesions as a major complication of abdominal surgery and
      the limited adhesion awareness.

PMID- 30118504
TI  - A multi-target brain-computer interface based on code modulated visual evoked
      potentials.
AB  - The number of selectable targets is one of the main factors that affect the
      performance of a brain-computer interface (BCI). Most existing code modulated
      visual evoked potential (c-VEP) based BCIs use a single pseudorandom binary
      sequence and its circularly shifting sequences to modulate different stimulus
      targets, making the number of selectable targets limited by the length of
      modulation codes. This paper proposes a novel paradigm for c-VEP BCIs, which
      divides the stimulus targets into four target groups and each group of targets
      are modulated by a unique pseudorandom binary code and its circularly shifting
      codes. Based on the paradigm, a four-group c-VEP BCI with a total of 64 stimulus
      targets was developed and eight subjects were recruited to participate in the BCI
      experiment. Based on the experimental data, the characteristics of the c-VEP BCI
      were explored by the analyses of auto- and cross-correlation, frequency spectrum,
      signal to noise ratio and correlation coefficient. On the basis, single-trial
      data with the length of one stimulus cycle were classified and the attended
      target was recognized. The averaged classification accuracy across subjects was
      88.36% and the corresponding information transfer rate was as high as 184.6
      bit/min. These results suggested that the c-VEP BCI paradigm is both feasible and
      effective, and provides a new solution for BCI study to substantially increase
      the number of available targets.

PMID- 30118507
TI  - The design and analysis of a new slipper-type hydraulic support.
AB  - To improve the safety and the stability of the support under mines and reduce the
      cost, we design a new slipper-type hydraulic support with energy-efficiency and
      high reliability. To study its dynamics, we build a reverse kinematics model. We
      analyze the motion and the force for each component of the new support with a
      simulation in Matlab/Simulink. The results show that it has appropriate
      structures with the required four-bar linkages. To compare the performance
      between the new slipper-type support and the traditional support, we design their
      mechanics models, deduce their mechanics relations and obtain the force curves
      for each component of both supports under the same loads. The results prove that
      the new slipper-type support has less demand on oil pressure for the hydraulic
      cylinder when working at middle and high positions and it has a larger supporting
      force and a higher supporting stability which would be more energy-efficient.

PMID- 30118505
TI  - Predicting acute renal failure in Bothrops snakebite patients in a tertiary
      reference center, Western Brazilian Amazon.
AB  - Acute Kidney Injury (AKI) is the main systemic complication and cause of death in
      viperid envenomation. Although there are hypotheses for the development of AKI,
      the mechanisms involved are still not established. The aim of this study was to
      evaluate the clinical-laboratorial-epidemiological factors associated with AKI in
      victims of Bothrops sp envenomation. This is an observational study carried out
      at the Fundacao de Medicina Tropical Dr. Heitor Vieira Dourado. AKI was defined
      according to the guidelines of the Acute Kidney Injury Network (AKIN). Among the
      186 patients evaluated, AKI was observed in 24 (12.9%) after 48 hours of
      admission. Stage I was present in 17 (70.8%) patients, II in 3 (12.5%) and III in
      4 (16.7%). Epidemiological characterization showed predominance of men,
      occurrence in rural areas, aged between 16-60 years, feet as the most affected
      anatomical region, and time to medical assistance less than 3 hours. Hypertension
      and diabetes were the comorbidities identified. Most of the accidents were
      classified as moderate, and clinical manifestations included severe pain, mild
      edema, local bleeding and headache. Laboratory results showed blood
      uncoagulability, hypofibrinogenemia, leukocytosis, increase of creatine kinase,
      and high lactate dehydrogenase levels. Multivariate analysis showed an
      association with high LDH levels [AOR = 1.01 (95% CI = 1.01-1.01, p<0.002)],
      local bleeding [AOR = 0.13 (95%CI = 0.027-0.59, p<0.009)], and the presence of
      comorbidities [AOR = 60.96 (95%CI = 9.69-383.30; p<0.000)]. Herein, laboratory
      markers such as high LDH levels along with local bleeding and comorbidities may
      aid in the diagnosis of AKI.

PMID- 30118506
TI  - Utility of including BRAF mutation analysis with ultrasonographic and cytological
      diagnoses in ultrasonography-guided fine-needle aspiration of thyroid nodules.
AB  - This study investigated the role of BRAF mutation analysis in thyroid fine-needle
      aspiration (FNA) samples compared to ultrasonographic and cytological diagnoses.
      A total 316 patients underwent ultrasonography (US)-guided FNA with BRAFV600E
      mutation analysis to diagnose thyroid nodules. One hundred sixteen patients with
      insufficient US images (n = 6), follow-up loss (n = 43), or unknown final
      diagnosis (n = 67) were excluded from the study. Comparisons between US
      diagnoses, cytological diagnoses, and BRAF mutation analysis were performed. Of
      200 thyroid nodules, there was US diagnosis with 1 false negative and 11 false
      positive cases, cytological diagnosis with 10 false negative and 2 false positive
      cases, and BRAFV600E mutation analysis with 19 false negative and 2 false
      positive cases. The sensitivity, specificity, positive and negative predictive
      values, and accuracy of BRAFV600E mutation analysis were 83.2%, 98.1%, 97.5%,
      86.6%, and 91%, respectively. Of the 18 nodules with Bethesda category III, 9
      were true positive, 6 were true negative, 3 was a false negative, and none were
      false positive on BRAF mutation analysis. In conclusion, we recommend that
      BRAFV600E mutation analysis only be performed for evaluating thyroid nodules with
      Bethesda category III, regardless of US diagnosis.

PMID- 30118508
TI  - Trends in cigarette demand and supply in Africa.
AB  - BACKGROUND: Since the tobacco epidemic is moving from developed to developing
      countries, it is important to understand trends in cigarette demand and supply.
      We focus on the African market since it offers the tobacco industry one of the
      best expansion potentials. DATA: A large variety of data from commercial
      (Canadean, Euromonitor International, tobacco industry reports), governmental
      (United Nations Comtrade, national statistics), and academic sources (Cigarette
      Citadels Map and journal articles) were utilized. METHODS: We compile data from
      multiple sources to study cigarette demand in Africa from 1990 to 2012. We then
      focus on cigarette production and international cigarette trade to detect
      structural changes in cigarette supply over the past few decades. We contrast
      data from these different sources. RESULTS: Cigarette demand and supply data in
      Africa is limited and is sometimes inconsistent across different sources. Given
      this caveat, we found that the overall demand for cigarettes (measured by sales)
      in the 22 countries covered by Canadean, which represents 80% of Africa's
      population, increased by 44% (from 165.6 billion cigarettes to 238.5 billion
      cigarettes) from 1990 to 2012. This higher demand has been met by cigarette
      production increasing in these 22 countries by 106% during the same period. As a
      result, Africa has moved from being a net importer to a net exporter of
      cigarettes. At the same time, cigarette production has become more concentrated
      as the tobacco industry has strategically identified certain countries as
      production hubs. CONCLUSIONS: Monitoring the production, consumption and trade of
      cigarettes by improving the quality of surveillance is necessary to understand
      the demand and supply of cigarettes not only in Africa, but globally.

PMID- 30118509
TI  - Comparisons between context-specific and beverage-specific quantity frequency
      instruments to assess alcohol consumption indices: Individual and sample level
      analysis.
AB  - There are many survey instruments to determine drinking patterns and alcohol
      consumption levels in the general population. This study aims to compare the
      context-specific quantity-frequency (CSQF) and beverage-specific quantity
      frequency (BSQF) methods to estimate alcohol consumption indices at individual
      and sample levels. A community-based cross-sectional study was conducted among a
      population aged 15 years and older in Songkhla Province, Thailand. The BSQF and
      CSQF questionnaires with a 3-month retrospective time frame and in random order
      were applied to each participant. The CSQF was developed to ask more about the
      drinking contexts. The questions elicited information on location, partner,
      beverage, quantity, and frequency for five common drinking situations. Among 804
      participants, 183 drank alcohol in the last three months. At the individual
      level, total alcohol consumption of almost all types of beverage by the CSQF was
      higher than the BSQF in approximately 50% of current drinkers and was mainly
      accounted for by the higher report of average quantity. At the sample level,
      there were no significant differences in the average daily intake, 3-month intake
      per drinker or per capita consumption between instruments. The interview duration
      and burden of answering the questions by the participants for the CSQF were not
      significantly higher than those for the BSQF. In summary, the fuller picture of
      drinking behaviors from the CSQF has several valuable methodological advantages
      and provides information allowing alcohol policies to be more directly specific
      to certain target populations or situations. The CSQF is a prototype
      questionnaire and forms the basis for a contextual approach. However, additional
      methodological studies need to be explored.

PMID- 30118510
TI  - The effects of extra high dose rate irradiation on glioma stem-like cells.
AB  - Radiation therapy is an integral part of treatment for patients with
      glioblastoma. New technological advances in linear accelerators have made extra
      high dose rate irradiation possible. This shortens patient treatment time
      significantly compared to standard dose rate irradiation, but the biologic
      effects of extra high dose rate irradiation are poorly understood. Glioma stem
      like cells (GSCs) are resistant to standard radiation and contribute to tumor
      progression. Here, we assess the therapeutic effect of extra high dose rate vs.
      standard dose rate irradiation on GSCs. GSCs were exposed to 2, 4 and 6 Gy X
      irradiation at dose rates of 4.2 Gy/min or 21.2 Gy/min (400 monitoring units
      (MU)/min or 2100 MU/min). We analyzed cell survival with cell growth assays,
      tumorsphere formation assays and colony formation assays. Cell kill and self
      renewal were dependent on the total dose of radiation delivered. However, there
      was no difference in survival of GSCs or DNA damage repair in GSCs irradiated at
      different dose rates. GSCs exhibited significant G1 and G2/M phase arrest and
      increased apoptosis with higher doses of radiation but there was no difference
      between the two dose rates at each given dose. In a GSC-derived preclinical model
      of glioblastoma, radiation extended animal survival, but there was no difference
      in survival in mice receiving different dose rates of radiation. We conclude that
      GSCs respond to larger fractions of radiation, but extra high dose rate
      irradiation has no significant biologic advantage in comparison with standard
      dose rate irradiation.

PMID- 30118511
TI  - Molecular basis for CesT recognition of type III secretion effectors in
      enteropathogenic Escherichia coli.
AB  - Enteropathogenic Escherichia coli (EPEC) use a needle-like injection apparatus
      known as the type III secretion system (T3SS) to deliver protein effectors into
      host cells. Effector translocation is highly stratified in EPEC with the
      translocated intimin receptor (Tir) being the first effector delivered into the
      host. CesT is a multi-cargo chaperone that is required for the secretion of Tir
      and at least 9 other effectors. However, the structural and mechanistic basis for
      differential effector recognition by CesT remains unclear. Here, we delineated
      the minimal CesT-binding region on Tir to residues 35-77 and determined the 2.74
      A structure of CesT bound to an N-terminal fragment of Tir. Our structure
      revealed that the CesT-binding region in the N-terminus of Tir contains an
      additional conserved sequence, distinct from the known chaperone-binding beta
      motif, that we termed the CesT-extension motif because it extends the beta-sheet
      core of CesT. This motif is also present in the C-terminus of Tir that we
      confirmed to be a unique second CesT-binding region. Point mutations that disrupt
      CesT-binding to the N- or C-terminus of Tir revealed that the newly identified
      carboxy-terminal CesT-binding region was required for efficient Tir translocation
      into HeLa cells and pedestal formation. Furthermore, the CesT-extension motif was
      identified in the N-terminal region of NleH1, NleH2, and EspZ, and mutations that
      disrupt this motif reduced translocation of these effectors, and in some cases,
      overall effector stability, thus validating the universality of this CesT
      extension motif. The presence of two CesT-binding regions in Tir, along with the
      presence of the CesT-extension motif in other highly translocated effectors, may
      contribute to differential cargo recognition by CesT.

PMID- 30118512
TI  - Stearoly-CoA desaturase 1 differentiates early and advanced dengue virus
      infections and determines virus particle infectivity.
AB  - Positive strand RNA viruses, such as dengue virus type 2 (DENV2) expand and
      structurally alter ER membranes to optimize cellular communication pathways that
      promote viral replicative needs. These complex rearrangements require significant
      protein scaffolding as well as changes to the ER chemical composition to support
      these structures. We have previously shown that the lipid abundance and
      repertoire of host cells are significantly altered during infection with these
      viruses. Specifically, enzymes in the lipid biosynthesis pathway such as fatty
      acid synthase (FAS) are recruited to viral replication sites by interaction with
      viral proteins and displayed enhanced activities during infection. We have now
      identified that events downstream of FAS (fatty acid desaturation) are critical
      for virus replication. In this study we screened enzymes in the unsaturated fatty
      acid (UFA) biosynthetic pathway and found that the rate-limiting enzyme in
      monounsaturated fatty acid biosynthesis, stearoyl-CoA desaturase 1 (SCD1), is
      indispensable for DENV2 replication. The enzymatic activity of SCD1, was required
      for viral genome replication and particle release, and it was regulated in a time
      dependent manner with a stringent requirement early during viral infection. As
      infection progressed, SCD1 protein expression levels were inversely correlated
      with the concentration of viral dsRNA in the cell. This modulation of SCD1,
      coinciding with the stage of viral replication, highlighted its function as a
      trigger of early infection and an enzyme that controlled alternate lipid
      requirements during early versus advanced infections. Loss of function of this
      enzyme disrupted structural alterations of assembled viral particles rendering
      them non-infectious and immature and defective in viral entry. This study
      identifies the complex involvement of SCD1 in DENV2 infection and demonstrates
      that these viruses alter ER lipid composition to increase infectivity of the
      virus particles.

PMID- 30118513
TI  - Spatial variation in the morphological traits of Pocillopora verrucosa along a
      depth gradient in Taiwan.
AB  - Pocillopora verrucosa is a widely distributed depth-generalist coral that
      presents plasticity in its skeletal macro- and microstructure in response to
      environmental gradients. Light and water movement, which covary with depth, are
      the main environmental drivers of morphological plasticity in this genus;
      however, assessing environmentally-induced plasticity may be confounded by the
      extent of interspecific variation in Pocillopora. We examine the morphology of 8
      typed P. verrucosa specimens collected along a depth gradient ranging from 7 to
      45 meters and comprising 3 sites throughout Ludao, Taiwan. We measured 36
      morphological characters, 14 which are novel, in 3 regions on the corallum-the
      apex, branch and base-in order to quantify their relationship to site and depth.
      We found significant correlation between depth and 19 morphological characters,
      notably branch verruca area, branch verruca height, base verruca spacing, base
      spinule length, and branch corallite area. 60% of microstructural characters and
      25% of macrostructural characters showed a correlative relation to depth,
      suggesting that depth acclimatization is manifested primarily at the
      microstructural level. Canonical discriminant analysis of all morphometric
      characters by depth supports clustering into 3 groups: an overlapping 7m and 15m
      group, a 23-30m group, and a 38-45m group. Canonical discriminant analysis by
      site supports clustering into low- and high-current sites, differentiated
      primarily by branch septa width, base septa width, pre-terminal branch width,
      terminal branch maximum length, and terminal branch minimum length. We conclude
      that distinctive patterns of morphological variation in mesophotic specimens of
      P. verrucosa could reflect the effects of abiotic parameters such as light and
      water flow. Elucidating the mechanisms behind the morphological changes that
      occur in response to environmental gradients can help clarify the role that
      physiological plasticity plays in the acclimatization of corals to the unique
      environmental settings of mesophotic coral ecosystems.

PMID- 30118514
TI  - (Pro)Renin receptor mediates obesity-induced antinatriuresis and elevated blood
      pressure via upregulation of the renal epithelial sodium channel.
AB  - Recent studies have demonstrated that the renal (pro)renin receptor (PRR)
      regulates expression of the alpha subunit of the epithelial sodium channel (alpha
      ENaC). In this study we hypothesized that the renal PRR mediates high fat diet
      (HFD)-induced sodium retention and elevated systolic blood pressure (SBP) by
      enhancing expression of the epithelial sodium channel (alpha-ENaC). In our study
      we used a recently developed inducible nephron specific PRR knockout mouse. Mice
      (n = 6 each group) were allocated to receive regular diet (RD, 12 kcal% fat) or a
      high-fat diet (HFD, 45 kcal% fat) for 10 weeks. Body weight (BW), SBP, urine
      volume (UV) and urine sodium (UNaV), as well as renal interstitial Angiotensin II
      (Ang II), and renal medullary expression of PRR, p-SGK-1, alpha-ENaC were
      monitored in RD and HFD mice with or without PRR knockout. At baseline, there
      were no significant differences in BW, BP, UV or UNaV between different animal
      groups. At the end of the study, HFD mice had significant increases in SBP, BW,
      and significant reductions in UV and UNaV. Compared to RD, HFD significantly
      increased mRNA and protein expression of PRR, alpha-ENaC, p-SGK-1, and Ang II.
      Compared to HFD alone, PRR knockout mice on HFD had reduced mRNA and protein
      expression of PRR, p-SGK-1, and alpha-ENaC, as well as increased UV, UNaV and
      significantly reduced SBP. RIF Ang II was significantly increased by HFD and did
      not change in response to PRR knockout. We conclude that obesity induced sodium
      retention and elevated SBP are mediated by the PRR-SGK-1- alpha-ENaC pathway
      independent of Ang II.

PMID- 30118515
TI  - Comprehensive analysis of differentially expressed microRNAs and mRNAs in dorsal
      root ganglia from streptozotocin-induced diabetic rats.
AB  - Diabetic peripheral neuropathy is a common complication associated with diabetes
      mellitus with a pathogenesis that is incompletely understood. By regulating RNA
      silencing and post-transcriptional gene expression, microRNAs participate in
      various biological processes and human diseases. However, the relationship
      between microRNAs and the progress of diabetic peripheral neuropathy still lacks
      a thorough exploration. Here we used microarray microRNA and mRNA expression
      profiling to analyze the microRNAs and mRNAs which are aberrantly expressed in
      dorsal root ganglia from streptozotocin-induced diabetic rats. We found that 37
      microRNAs and 1357 mRNAs were differentially expressed in comparison to non
      diabetic samples. Bioinformatics analysis indicated that 399 gene ontology terms
      and 29 Kyoto Encyclopedia of Genes and Genomes pathways were significantly
      enriched in diabetic rats. Additionally, a microRNA-gene network evaluation
      identified rno-miR-330-5p, rno-miR-17-1-3p and rno-miR-346 as important players
      for network regulation. Finally, quantitative real-time polymerase chain reaction
      analysis was used to confirm the microarray results. In conclusion, this study
      provides a systematic perspective of microRNA and mRNA expression in dorsal root
      ganglia from diabetic rats, and suggests that dysregulated microRNAs and mRNAs
      may be important promotors of peripheral neuropathy. Our results may be the
      underlying framework of future studies regarding the effect of the aberrantly
      expressed genes on the pathophysiology of diabetic peripheral neuropathy.

PMID- 30118516
TI  - Risk factors for radioactive iodine-avid metastatic lymph nodes on post I-131
      ablation SPECT/CT in low- or intermediate-risk groups of papillary thyroid
      cancer.
AB  - OBJECTIVE: Post I-131 ablation single-photon emission computed tomography
      (SPECT)/CT can show radioactive iodine (RAI)-avid cervical metastatic lymph nodes
      (mLN) in differentiated thyroid cancer. This study aimed to evaluate the
      incidence of RAI-avid mLN on post I-131 ablation SPECT/CT and the risk factors
      related to metastasis among patients with papillary thyroid cancer (PTC) in the
      low- or intermediate-risk groups. STUDY DESIGN AND SETTING: Among 339 patients
      with PTC who underwent total thyroidectomy followed by I-131 ablation, 292 (228
      women, 64 men) belonging to the low- or intermediate-risk groups before I-131
      ablation, and with sufficient clinical follow-up data were enrolled. The risk
      groups were classified based on the American Thyroid Association 2015 guideline.
      Each patient was followed-up for at least 24 months after the ablation (median:
      30 months). The clinical, pathologic, and biochemical factors of PTC were
      reviewed, and their relationships to RAI-avid mLN on SPECT/CT were analyzed.
      RESULTS: Of the 292 patients, 61 and 231 belonged to the low-and intermediate
      risk groups, respectively. Four (6.5%) patients in the low-risk group and 31
      (13.0%) patients in the intermediate-risk group had RAI-avid mLN. A high
      preablation TSH-stimulated serum thyroglobulin (Tg) level in the low- or
      intermediate-risk group predicted the presence of RAI-avid mLN (cut-off = 0.5;
      hazard ratio (HR): 2.96; p = 0.04). In the subgroup analysis by risk group, TSH
      stimulated serum Tg only predicted RAI-avid mLN in the low-risk group (cut-off =
      1.0; HR: 5.3; p = 0.03). CONCLUSION: The incidence of RAI-avid mLN on
      postablation SPECT/CT was relatively high in both low- and intermediate-risk
      patients with PTC, and high preablation TSH-stimulated serum Tg level was a
      predictor of metastasis, especially in the low-risk group. A selective treatment
      approach should be considered in patients with high preablation TSH-stimulated
      serum Tg level.

PMID- 30118517
TI  - Population genetic analysis of aquaculture salmonid populations in China using a
      57K rainbow trout SNP array.
AB  - Various salmonid species are cultivated in cold water aquaculture. However, due
      to limited genomic data resources, specific high-throughput genotyping tools are
      not available to many of the salmonid species. In this study, a 57K single
      nucleotide polymorphism (SNP) array for rainbow trout (Oncorhynchus mykiss) was
      utilized to detect polymorphisms in seven salmonid species, including Hucho
      taimen, Oncorhynchus masou, Salvelinus fontinalis, Brachymystax lenok, Salvelinus
      leucomaenis, O. kisutch, and O. mykiss. The number of polymorphic markers per
      population ranged from 3,844 (O. kisutch) to 53,734 (O. mykiss), indicating that
      the rainbow trout SNP array was applicable as a universal genotyping tool for
      other salmonid species. Among the six other salmonid populations from four
      genera, 28,882 SNPs were shared, whereas 525 SNPs were polymorphic in all four
      genera. The genetic diversity and population relationships of the seven salmonid
      species were studied by principal component analysis (PCA). The phylogenetic
      relationships among populations were analyzed using the maximum likelihood
      method, which indicated that the shared SNP markers provide reliable genomic
      information for population genetic analyses in common aquaculture salmonid
      fishes. Furthermore, this obtained genomic information may be applicable for
      population genetic evaluation, marker-assisted breeding, and propagative parent
      selection in fry production.

PMID- 30118518
TI  - Association of high titers of anti-carbamylated protein antibodies with decreased
      bone mineral density in early arthritis patients.
AB  - Rheumatoid arthritis (RA) has a negative impact on bone that is partly mediated
      by anti-citrullinated proteins antibodies (ACPA). These antibodies are associated
      with erosions, and with juxta-articular and systemic bone loss. Other RA
      autoantibodies, the anti-carbamylated protein antibodies (anti-CarPA), are
      independently associated with erosions. However, we do not know if they are also
      associated with juxta-articular and systemic bone loss. Here, we have addressed
      this question with data from 548 early arthritis (EA) patients. Bone mineral
      density (BMD) was assessed by dual-energy x-ray absorptiometry at the lumbar
      spine (LS), total hip (TH) and metacarpophalangeal joints (MCP). The 25.9% anti
      CarPA positive patients did not show significant differences in BMD Z-scores with
      the negative patients. Nevertheless, this result was due to the similarity
      between negative and low-positive (below the median of the positive) patients,
      whereas the high-positive patients showed significant decrease of BMD at LS (beta
      = -0.39, p = 0.01) and TH (beta = -0.30, p = 0.02); but not at the juxta
      articular bone of MCP. Given the overlap between anti-CarPA and ACPA, we included
      the two autoantibodies in an analysis that showed significantly lower BMD Z
      scores at LS and TH (p< 0.01) only in the ACPA positive/anti-CarPA high-positive
      subgroup. However, the similar coefficients of regression between the ACPA
      positive/anti-CarPA high-positive and the ACPA negative/anti-CarPA high-positive
      subgroups (beta = -0.50 vs. -0.52 at LS, and beta = -0.37 vs. -0.30 at TH)
      suggested an independent association. Overall, these results support a
      contribution of anti-CarPA to systemic bone loss in EA patients.

PMID- 30118519
TI  - Predictors of death including quality of positive pressure ventilation during
      newborn resuscitation and the relationship to outcome at seven days in a rural
      Tanzanian hospital.
AB  - BACKGROUND: Effective positive pressure ventilation (PPV) of non-breathing
      newborns is crucial in facilitating cardio-respiratory adaptation at birth.
      Identifying predictors of death in newborns receiving PPV is important in order
      to facilitate preventative strategies. OBJECTIVE: The objective of this study was
      to determine the perinatal predictors of death including the quality of PPV
      administered among admitted newborns. METHODS: An observational study of admitted
      newborns who received PPV after birth was conducted. Research assistants observed
      all deliveries and recorded perinatal events on data collection forms. Measured
      heart rate (HR) and ventilation parameters were then compared between newborns
      who died and survivors. RESULTS: Newborns (n = 232) were studied between October
      2014 and November 2016. Newborns who died (n = 53) compared to survivors (n =
      179) had more fetal heart rate (FHRT) abnormalities (12/53 vs 19/179; p = 0.03);
      lower initial HR (<100 beats/minute) at start of PPV (44/48 vs 77/139; p<0.001);
      and a longer time for HR to increase >100 beats/minute from birth (180 vs 149
      seconds; p = 0.07). Newborns who died compared to survivors took longer time (14
      vs 4 seconds; p = 0.008) and more inflations (7 vs 3; p = 0.006) to achieve an
      expired volume (Vt) of 6 ml/kg, respectively. Median delivered Vt during the
      first 60 seconds of PPV was less in newborns who died compared to survivors (5 vs
      6 ml/kg; p = 0.12). Newborns who died proceeded to severe encephalopathy (15/31
      vs 1/59; p<0.001) compared to survivors. CONCLUSION: Depressed newborns who
      proceeded to death compared to survivors, exhibited delayed HR response to PPV
      which may partly reflect FHRT abnormalities related to interruption of placental
      blood flow, and/or a timely delay in establishing adequate Vt. Depressed newborns
      progressed to moderate/severe encephalopathy. Improving FHRT monitoring to
      identify fetuses at risk for expedited delivery, coupled with optimizing delivery
      room PPV might decrease mortality in this setting.

PMID- 30118520
TI  - Inter-rater agreement in trait judgements from faces.
AB  - Researchers have long been interested in how social evaluations are made based
      upon first impressions of faces. It is also important to consider the level of
      agreement we see in such evaluations across raters and what this may tell us.
      Typically, high levels of inter-rater agreement for facial judgements are
      reported, but the measures used may be misleading. At present, studies commonly
      report Cronbach's alpha as a way to quantify agreement, although problematically,
      there are various issues with the use of this measure. Most importantly, because
      researchers treat raters as items, Cronbach's alpha is inflated by larger sample
      sizes even when agreement between raters is fixed. Here, we considered several
      alternative measures and investigated whether these better discriminate between
      traits that were predicted to show low (parental resemblance), intermediate
      (attractiveness, dominance, trustworthiness), and high (age, gender) levels of
      agreement. Importantly, the level of inter-rater agreement has not previously
      been studied for many of these traits. In addition, we investigated whether
      familiar faces resulted in differing levels of agreement in comparison with
      unfamiliar faces. Our results suggest that alternative measures may prove more
      informative than Cronbach's alpha when determining how well raters agree in their
      judgements. Further, we found no apparent influence of familiarity on levels of
      agreement. Finally, we show that, like attractiveness, both trustworthiness and
      dominance show significant levels of private taste (personal or idiosyncratic
      rater perceptions), although shared taste (perceptions shared with other raters)
      explains similar levels of variance in people's perceptions. In conclusion, we
      recommend that researchers investigating social judgements of faces consider
      alternatives to Cronbach's alpha but should also be prepared to examine both the
      potential value and origin of private taste as these might prove informative.

PMID- 30118521
TI  - Predictive value of soluble ST2 in adolescent and adult patients with complex
      congenital heart disease.
AB  - BACKGROUND: Soluble suppression of tumorogenicity 2 (sST2) has been shown to be
      of prognostic value in patients with chronic and acute left heart failure. The
      present study aims to assess the predictive value of sST2 levels in adult
      patients with complex congenital heart disease (CHD). METHODS: In 169 consecutive
      patients with complex CHD and a mean age of 28.2 +/- 12.0 years, sST2 levels were
      compared to 32 healthy controls and associated with clinical status as well as
      the occurrence of major adverse cardiac events (MACE). Mean follow-up time was
      35.6 +/- 24.9 months. RESULTS: In CHD patients, median sST2 levels were 29.7
      ng/ml compared to 26.4 ng/ml in healthy controls (p = 0.007) and increased with
      different types of CHD and the severity of MACE. According to ROC analysis, the
      most important predictors of acute heart/Fontan failure were NYHA class III/IV
      (AUC 0.804, p<0.001, CI 0.668-0.941), NT-proBNP levels (AUC 0.794, p<0.001, CI
      0.640-0.948), gammaGT levels (AUC 0.793, p<0.001, CI 0.678-0.909) and sST2 levels
      (AUC 0.742, p = 0.004, CI 0.626-0.858), with NYHA class III/IV as the strongest
      independent predictor (p<0.001). All-cause mortality was best predicted by sST2
      levels (AUC 0.890, p<0.001, CI 0.741-1.000), NT-proBNP levels (AUC 0.875, p =
      0.001, CI 0.766-0.984) and NYHA class III/IV (AUC 0.837, p = 0.003, CI 0.655
      1.000) with sST2 as the strongest independent predictor (p<0.001). Moreover, AUC
      increased to 0.918 combining both biomarkers and net reclassification improved
      with the addition of sST2. CONCLUSION: In patients with complex CHD, sST2 may
      have additive value to natriuretic peptides for the prediction of all-cause
      mortality.

PMID- 30118522
TI  - Selection on the Colombian paso horse's gaits has produced kinematic differences
      partly explained by the DMRT3 gene.
AB  - The Colombian paso horse, the most important horse breed in Colombia, performs
      specific and particular gaits (paso fino, trocha, and Colombian trot), which
      display different footfall patterns and stride frequencies. The breed has been
      selected for gait and conformation for more than 50 years and we hypothesize that
      this selection has led to kinematic differences of the gaits that can be
      explained by different genetic variants. Hence, the aims of the study were: 1. To
      identify if there are any differences in the kinematic and genetic variants
      between the Colombian paso horse's gaits. 2. To evaluate if and how much the gait
      differences were explained by the nonsense mutation in the DMRT3 gene and 3. To
      evaluate these results for selecting and controlling the horses gait performance.
      To test our hypotheses, kinematic data, microsatellites and DMRT3 genotypes for
      187 Colombian paso horses were analyzed. The results indicated that there are
      significant kinematic and DMRT3 differences between the Colombian paso horse's
      gaits, and those parameters can be used partially to select and control the
      horses gait performance. However, the DMRT3 gene does not play a major role in
      controlling the trocha and the Colombian trot gaits. Therefore, modifying genes
      likely influence these gaits. This study may serve as a foundation for
      implementing a genetic selection program in the Colombian paso horse and future
      gene discovery studies for locomotion pattern in horses.

PMID- 30118523
TI  - Parameter estimation using randomized phases in an integrated assessment model
      for Antarctic krill.
AB  - An integrated model assessing the status and productivity of Antarctic krill
      (Euphausia superba, hereafter krill) was configured to estimate different subsets
      of 118 potentially estimable parameters in alternative configurations. We fixed
      the parameters that were not estimated in any given configuration at pre
      specified values. The model was fitted to over forty years of fisheries and
      survey data for krill in Subarea 48.1, a statistical reporting area around the
      Antarctic Peninsula used by the Commission for the Conservation of Antarctic
      Marine Living Resources (CCAMLR). The number of estimated parameters was
      gradually increased across model configurations. Configurations that estimated
      more parameters fitted the data better, but the order in which the parameters
      were estimated became more important in finding the best fit. Twenty-two
      configurations estimating from 48 to 107 parameters were able to obtain an
      invertible Hessian matrix that was subsequently used to estimate parameter
      uncertainty. Parameter uncertainties calculated using asymptotic approximation
      around the maximum likelihood estimates were often larger than uncertainties
      based on Markov chain Monte Carlo sampling for the same parameters. Diagnostics
      applied to MCMC samples in the best model of each configuration that obtained an
      invertible Hessian indicated that the most highly parameterized configurations
      did not reach stationary distributions. A 96-parameter configuration was the best
      fitting model of those that passed the MCMC diagnostics. The DeltaAIC and
      DeltaBIC scores indicated essentially no support relative to the best model for
      the alternative models that also passed MCMC diagnostics. Simulated data using
      the configurations as operating models showed that while all configurations
      passed "self-tests" for spawning biomass and recruitment, there was a small
      negative bias due to model penalties in the fishing mortality estimates for years
      with the highest fishing mortalities. "Cross-tests" of configurations that
      estimated different parameters often differed from the operating model values.

PMID- 30118524
TI  - Divergent genetic mechanism leads to spiny hair in rodents.
AB  - Spines, or modified hairs, have evolved multiple times in mammals, particularly
      in rodents. In this study, we investigated the evolution of spines in six rodent
      families. We first measured and compared the morphology and physical properties
      of hairs between paired spiny and non-spiny sister lineages. We found two
      distinct hair morphologies had evolved repeatedly in spiny rodents: hairs with a
      grooved cross-section and a second near cylindrical form. Compared to the
      ancestral elliptical-shaped hairs, spiny hairs had higher tension and stiffness,
      and overall, hairs with similar morphology had similar functional properties. To
      examine the genetic basis of this convergent evolution, we tested whether a
      single amino acid change (V370A) in the Ectodysplasin A receptor (Edar) gene is
      associated with spiny hair, as this substitution causes thicker and straighter
      hair in East Asian human populations. We found that most mammals have the common
      amino acid valine at position 370, but two species, the kangaroo rat (non-spiny)
      and spiny pocket mouse (spiny), have an isoleucine. Importantly, none of the
      variants we identified are associated with differences in rodent hair morphology.
      Thus, the specific Edar mutation associated with variation in human hair does not
      seem to play a role in modifying hairs in wild rodents, suggesting that different
      mutations in Edar and/or other genes are responsible for variation in the spiny
      hair phenotypes we observed within rodents.

PMID- 30118525
TI  - TLR4-mediated activation of the ERK pathway following UVA irradiation contributes
      to increased cytokine and MMP expression in senescent human dermal fibroblasts.
AB  - Exposure to ultraviolet (UV) radiation is a major contributing factor to
      premature aging (photoaging) and skin cancer. In vitro models of cellular
      senescence have proven to be very useful for the study of slow and progressive
      accumulation of damage resulting in the growth arrest of aging skin cells. In
      this study, we compared UVA-induced cellular responses in non-senescent (NS) vs.
      senescent (S) human dermal fibroblasts (HDFs). HDFs were irradiated with a single
      dose of UVA (7.5 J/cm2) and QuantSeq 3' mRNA sequencing was performed to assess
      differential gene expression. Both NS and S HDFs expressed similar numbers of
      differentially expressed genes, although distinct sets of genes were
      differentially expressed between the two groups. Higher expression of matrix
      metalloproteinases (MMPs) and Toll-like receptor (TLR) pathway genes, such as
      TLR4, MyD88, and CXCL-8, was detected in S HDFs as compared with NS HDFs, and UVA
      exposure led to a downregulation of collagen genes, such as COL8A2 and COL5A3.
      Consistent with gene expression profiling, enhanced IL-6 and IL-8 secretion was
      observed in S HDFs compared with NS HDFs, in response to UVA. Furthermore, we
      show that TLR4-mediated ERK pathway is responsible for the UVA-mediated
      mitochondrial dysfunction as well as increased secretion of MMP-1 and IL-8 in S
      HDFs. Taken together, our results demonstrate the UVA-induced common and distinct
      molecular patterns of cellular responses between NS and S HDFs and suggest
      TLR4/ERK pathways as candidate targets to reduce senescent phenotypes.

PMID- 30118526
TI  - Defining the genetic components of callus formation: A GWAS approach.
AB  - A characteristic feature of plant cells is the ability to form callus from
      parenchyma cells in response to biotic and abiotic stimuli. Tissue culture
      propagation of recalcitrant plant species and genetic engineering for desired
      phenotypes typically depends on efficient in vitro callus generation. Callus
      formation is under genetic regulation, and consequently, a molecular
      understanding of this process underlies successful generation for propagation
      materials and/or introduction of genetic elements in experimental or industrial
      applications. Herein, we identified 11 genetic loci significantly associated with
      callus formation in Populus trichocarpa using a genome-wide association study
      (GWAS) approach. Eight of the 11 significant gene associations were consistent
      across biological replications, exceeding a chromosome-wide-log10 (p) = 4.46 [p =
      3.47E-05] Bonferroni-adjusted significance threshold. These eight genes were used
      as hub genes in a high-resolution co-expression network analysis to gain insight
      into the genome-wide basis of callus formation. A network of positively and
      negatively co-expressed genes, including several transcription factors, was
      identified. As proof-of-principle, a transient protoplast assay confirmed the
      negative regulation of a Chloroplast Nucleoid DNA-binding-related gene
      (Potri.018G014800) by the LEC2 transcription factor. Many of the candidate genes
      and co-expressed genes were 1) linked to cell division and cell cycling in plants
      and 2) showed homology to tumor and cancer-related genes in humans. The GWAS
      approach based on a high-resolution marker set, and the ability to manipulate
      targets genes in vitro, provided a catalog of high-confidence genes linked to
      callus formation that can serve as an important resource for successful
      manipulation of model and non-model plant species, and likewise, suggests a
      robust method of discovering common homologous functions across organisms.

PMID- 30118528
TI  - Flapless Postextraction Socket Implant Placement: The Effects of a Platform
      Switch-Designed Implant on Peri-implant Soft Tissue Thickness-A Prospective
      Study.
AB  - This paper presents the results of a prospective study on the clinical effect of
      grafting the buccal gap with platform switching, following flapless tooth
      extraction and immediate implant placement and provisional restoration, on (1)
      alterations in buccolingual ridge dimension and (2) midfacial peri-implant soft
      tissue thickness. Fifty-six patients were placed in one of four treatment groups:
      (1) a non-platform-switching implant (Non-PS, n = 14); (2) a non-platform
      switching implant and bone graft (BG/Non-PS, n = 14); (3) a platform-switching
      implant (PS, n = 15); and (4) a platform-switching implant and bone graft (BG/PS,
      n = 13). Buccolingual ridge dimensional change and peri-implant soft tissue
      thickness at 2 mm below the free gingival margin were measured. Both PS and BG/PS
      groups showed an increase in buccolingual dimension compared to the contralateral
      natural tooth site as well as peri-implant soft tissue thickness of > 2.5 mm,
      clinically. Platform switching was associated with significantly greater
      midfacial soft tissue thickness than bone grafting (mean +/- standard deviation:
      2.17 +/- 0.04 for Non-PS and 3.55 +/- 0.14 for PS). Using platform-switched
      implants, in conjunction with immediate implant placement and immediate
      provisional restoration, was associated with a significantly greater stability of
      ridge dimension and peri-implant soft tissue thickness than using non-platform
      switched implants when measured 12 months after placement of the final
      restoration. Platform switching may help achieve preservation of ridge dimension
      and enhance the stability of peri-implant soft tissue following immediate implant
      placement and provisional restoration without bone grafting. Further research is
      required to assess the long-term outcome.

PMID- 30118529
TI  - Prospective Multicenter Clinical Cohort Study of a Novel Macro Hybrid Implant in
      Maxillary Anterior Postextraction Sockets: 1-Year Results.
AB  - A prospective cohort clinical study was performed to evaluate the concept and
      design of a novel macro hybrid implant placed into maxillary anterior
      postextraction sockets. Thirty-three patients with an equal number of hybrid
      implants were used to replace nonrestorable single anterior teeth with immediate
      tooth replacement therapy (immediate implant placement and immediate provisional
      restoration). The macro features of this hybrid implant are unique in geometry,
      as it combines two different shapes-a cylindrical coronal and tapered apical
      portion-into a singular body design, each comprising roughly half of the implant
      length. The hybrid design of this platform-switched implant also has a subcrestal
      angle correction, or Co-Axis feature, that facilitates screw-retained
      restorations. Mean implant survival at 1 year relative to primary stability,
      labial bone plate thickness with socket grafting at two reference points (L1 and
      L2), tooth-to-implant interproximal bone crest thickness, and pink esthetic score
      (PES) were evaluated. A mean insertion torque value of 65 Ncm (range 45 to 100
      Ncm) was reached with the use of the tapered apical half of the implant body. No
      implants failed during an average healing period of 1 year. A labial plate
      dimension between 1.8 and 2.1 mm was attained immediately posttreatment and
      remained stable over time. A tooth-to-implant interdental bone crest distance and
      dimension of 2.3 to 2.6 mm was reached; it was also sustained at the 1-year
      follow-up. The average PES was 12.5 (range 9.0 to 14.0), with nearly 90% of
      treated sites with an "almost perfect" score. This macro hybrid implant in
      concept and design may be useful in immediate tooth replacement therapy of
      maxillary anterior postextraction sockets to achieve successful implant survival
      and esthetic outcomes, specifically labial plate and papilla preservation without
      midfacial or interdental tissue loss and discoloration.

PMID- 30118527
TI  - Comparison of eight 15-lipoxygenase (LO) inhibitors on the biosynthesis of 15-LO
      metabolites by human neutrophils and eosinophils.
AB  - Neutrophils and eosinophils are important sources of bioactive lipids from the 5-
      and the 15-lipoxygenase (LO) pathways. Herein, we compared the effectiveness of
      humans eosinophils and eosinophil-depleted neutrophils to synthesize 15-LO
      metabolites using a cocktail of different 15-LO substrates as well as their
      sensitivities to eight documented 15-lipoxygenase inhibitors. The treatment of
      neutrophils and eosinophils with linoleic acid, dihomo-gamma-linolenic acid,
      arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid and arachidonyl
      ethanolamide, led to the synthesis of 13-HODE, 15-HETrE, 15-HETE, 15-HEPE, 14
      HDHA/17-HDHA, and 15-hydroxy-AEA. Neutrophils and eosinophils also metabolized
      the endocannabinoid 2-arachidonoyl-glycerol into 15-HETE-glycerol, although this
      required 2-arachidonoyl-glycerol hydrolysis inhibition. Neutrophils and
      eosinophils differed in regard to dihomo-gamma-linolenic acid and linoleic acid
      utilization with 15-HETrE/13-HODE ratios of 0.014 +/- 0.0008 and 0.474 +/- 0.114
      for neutrophils and eosinophils respectively. 15-LO metabolite synthesis by
      neutrophils and eosinophils also differed in regard to their relative production
      of 17-HDHA and 14-HDHA.The synthesis of 15-LO metabolites by neutrophils was
      concentration-dependent and rapid, reaching a plateau after one minute. While
      investigating the biosynthetic routes involved, we found that eosinophil-depleted
      neutrophils express the 15-lipoxygenase-2 but not the 15-LO-1, in contrast to
      eosinophils which express the 15-LO-1 but not the 15-LO-2. Moreover, 15-LO
      metabolite synthesis by neutrophils was not inhibited by the 15-LO-1 inhibitors
      BLX769, BLX3887, and ML351. However, 15-LO product synthesis was partially
      inhibited by 100 MUM NDGA. Altogether, our data indicate that the best 15-LO-1
      inhibitors in eosinophils are BLX3887, BLX769, NDGA and ML351 and that the
      synthesis of 15-LO metabolites by neutrophils does not involve the 15-LO-1 nor
      the phosphorylation of 5-LO on Ser-663 but is rather the consequence of 15-LO-2
      or another unidentified 15-LO.

PMID- 30118530
TI  - Alveolar Ridge Preservation Using Tridimensional Collagen Matrix and
      Deproteinized Bovine Bone Mineral in the Esthetic Area: A CBCT and Histologic
      Human Pilot Study.
AB  - Alveolar ridge preservation is of great importance for successful implant
      therapy. This study investigated the effects of a xenogeneic tridimensional
      collagen matrix (CM) in conjunction with deproteinized bovine bone mineral
      blended with 10% collagen (DBBM-C) on the healing of 12 intact extraction sockets
      in the esthetic area. Cone beam computed tomograpy examinations revealed nearly
      stable alveolar ridge dimensions (> 90% of the ridge horizontal dimension was
      preserved). New bone formation of approximately 45% and adequate resorption of
      the grafted material were histologically observed. Thus, application of CM
      together with DBBM-C using minimally invasive flapless approach can preserve the
      original ridge volume and support bone formation, contributing to adequate bone
      volume for implant insertion.

PMID- 30118531
TI  - The Biocompatibility of Cyanoacrylate Tissue Adhesive in Conjunction with a
      Collagen Membrane for Providing Soft and Hard Tissue Regeneration in Extraction
      Socket Preservation Procedures.
AB  - This clinical investigation was performed to determine the efficacy of
      cyanoacrylate tissue adhesive to enhance soft and hard tissue healing of
      extraction wounds requiring a regenerative effort. Fourteen patients requiring a
      total of 25 tooth extractions were selected. Twenty sockets were treated with
      cyanoacrylate tissue adhesive over an exposed collagen barrier membrane without
      altering the mucogingival junction, while five extraction sockets were allowed to
      heal by the secondary healing intention as well but without tissue adhesive
      application. The results were evaluated with emphasis on soft tissue color and
      form as well as bone surface morphology. All sites received dental implants.
      There was a clear advantage to using cyanoacrylate tissue adhesive as a
      protective mechanism over an exposed collagen barrier membrane.

PMID- 30118532
TI  - Treatment of Physiologic Gingival Pigmentation with Surgical Blade: A 25-Year
      Follow-up.
AB  - Gingival hyperpigmentation in the anterior region in people with a high smile
      line is an esthetic concern. Gingival depigmentation can be achieved through
      various procedures. Most techniques have shown successful short-term results;
      however, recurrence is observed in 50% of patients after 2 to 4 years. A 46-year
      old woman presenting with a large black zone of gingival hyperpigmentation in the
      anterior maxilla was treated with scalpel blade excision. At 25 years after the
      depigmentation procedure, the patient displayed no recurrence.

PMID- 30118533
TI  - A Randomized Controlled Clinical Trial Comparing Conventional and Computer
      Assisted Implant Planning and Placement in Partially Edentulous Patients. Part 1:
      Clinician-Related Outcome Measures.
AB  - The objectives of this study were to compare conventional and computer-assisted
      implant planning and placement (CAIPP) protocols regarding surgical planning
      predictability, intraoperative complications, and patient-centered outcomes.
      Partially edentulous patients (N = 73) were randomly allocated to one of three
      treatment groups: control (C, n = 26), with preoperative planning based on
      conventional radiography and freehand implant placement; and test 1 (T1, n = 24)
      and test 2 (T2, n = 23), with two different CAIPP protocols. The clinicians'
      predictions of the bony morphology, materials needed for surgery, and surgery
      duration were matched with intrasurgical findings using kappa tests.
      Complications or deviations from the surgical or prosthetic protocol were
      recorded. Descriptive statistics were used to study the sample sorted out by
      treatment group. Differences between groups were evaluated with chi-square test
      for qualitative variables and with nonparametric Kruskal-Wallis test for
      quantitative continuous variables. For post-hoc tests, the Bonferroni corrected
      (P < .016 = .05/3) Mann-Whitney test was used. CAIPP protocols showed better
      diagnostic potential than conventional protocols for the bone topography, need
      for simultaneous GBR procedures, membrane selection, and implant length
      predictions. The rate of surgical protocol deviations was similar in all groups,
      but their nature differed. Conventional protocols showed fewer splint-related
      incidences. Implant bed preparation and insertion could not be fully completed
      using the surgical splint in 3.8% of patients in C (1/26), 45.8% in T1 (11/24),
      and 47.8% in T2 (11/23). Deviation from the initial prosthetic plan was necessary
      in one case (T2; 4.4%). No biologic or technical complications were observed.
      CAIPP protocols showed a higher diagnostic potential than conventional protocols.
      A high incidence of intraoperative surgical protocol modifications to adjust
      suboptimal implant placements was reported for every group. Therefore, strict
      intraoperative implant position monitoring is mandatory for both treatment
      protocols.

PMID- 30118534
TI  - Nonincised Papillae Surgical Approach (NIPSA) in Periodontal Regeneration:
      Preliminary Results of a Case Series.
AB  - A new surgical approach has been developed to optimize the preservation of the
      gingival margin and papillae when treating periodontal defects. The flap is
      raised by one mucosal incision far away from the marginal tissues. This case
      series reports on the effectiveness of a nonincised surgical approach (NIPSA) in
      conjunction with a hydroxyapatite-based graft biomaterial and enamel matrix
      derivative in treating intrabony defects. Ten defects in 10 patients were
      treated. The follow-up period ranged from 6 to 18 months (mean: 10.8 +/- 4.7
      months). Probing pocket depth was 9.6 +/- 2.3 mm before surgery and 2.3 +/- 0.5
      mm postsurgery. Clinical attachment level (CAL) decreased from 10.4 +/- 2.7 mm to
      3.1 +/- 0.87 mm postsurgery. The gingival papilla height, keratinized tissue
      width, and buccal gingival margin remained stable over time. No wound dehiscence
      was recorded. Mean Early Healing Index was 1.5 +/- 0.7. Results show a
      substantial CAL gain, limited postsurgical shrinkage, minimal morbidity, and
      early healing.

PMID- 30118535
TI  - TpTe and TpTe/QT: novel markers to predict sudden cardiac death in ESRD?
AB  - INTRODUCTION: Reliable markers to predict sudden cardiac death (SCD) in patients
      with end stage renal disease (ESRD) remain elusive, but echocardiogram (ECG)
      parameters may help stratify patients. Given their roles as markers for
      myocardial dispersion especially in high risk populations such as those with
      Brugada syndrome, we hypothesized that the Tpeak to Tend (TpTe) interval and
      TpTe/QT are independent risk factors for SCD in ESRD. METHODS: Retrospective
      chart review was conducted on a cohort of patients with ESRD starting
      hemodialysis. Patients were US veterans who utilized the Veterans Affairs medical
      centers for health care. Average age of all participants was 66 years and the
      majority were males, consistent with a US veteran population. ECGs that were
      performed within 18 months of dialysis initiation were manually evaluated for
      TpTe and TpTe/QT. The primary outcomes were SCD and all-cause mortality, and
      these were assessed up to 5 years following dialysis initiation. RESULTS: After
      exclusion criteria, 205 patients were identified, of whom 94 had a prolonged
      TpTe, and 61 had a prolonged TpTe/QT interval (not mutually exclusive). Overall
      mortality was 70.2% at 5 years and SCD was 15.2%. No significant difference was
      observed in the primary outcomes when examining TpTe (SCD: prolonged 16.0% vs.
      normal 14.4%, p=0.73; all-cause mortality: prolonged 55.3% vs. normal 47.7%,
      p=0.43). Likewise, no significant difference was found for TpTe/QT (SCD:
      prolonged 15.4% vs. normal 15.0%, p=0.51; all-cause mortality: prolonged 80.7%
      vs. normal 66.7%, p=0.39). CONCLUSIONS: In ESRD patients on hemodialysis,
      prolonged TpTe or TpTe/QT was not associated with a significant increase in SCD
      or all-cause mortality.

PMID- 30118536
TI  - Inflammation and kidney injury attenuated by prior intake of Brazil nuts in the
      process of ischemia and reperfusion.
AB  - INTRODUCTION: Ischemia and reperfusion (IR) is a process inherent to the
      procedures involved in the transplantation of organs that causes inflammation,
      cell death and cell injury, and may lead to rejection of the graft. It is
      possible that the anti-inflammatory properties of the Brazil nuts (BN) can
      mitigate the renal injury caused by IR. OBJECTIVE: To investigate whether the
      previous intake of BN reduces the expression of markers of inflammation, injury,
      and cell death after renal IR. METHODS: Male Wistar rats were distributed into
      six groups (N = 6/group): SHAM (control), SHAM treated with 75 or 150 mg of BN,
      IR, and IR treated with 75 or 150 mg of BN. The IR procedure consisted of right
      nephrectomy and occlusion of the left renal artery with a non-traumatic vascular
      clamp for 30 min. BN was given daily from day 1 to 7 before surgery (SHAM or IR),
      and maintained until sacrifice (48 h after surgery). Inflammation was evaluated
      by renal expression of COX-2 and TGF-beta, injury by the expression of vimentin,
      and cell death by apoptosis through caspase-3 expression (immunohistochemistry).
      RESULTS: Pretreatment with 75 mg of BN reduced renal expression of the COX-2, TGF
      beta, vimentin, and caspase-3. The dose of 150 mg caused increased expression of
      COX-2. CONCLUSION: In experimental IR, the damage can be minimized with a prior
      low-dose intake of BN, improving inflammation, injury, and cell death.

PMID- 30118537
TI  - Effects of non-surgical periodontal therapy on clinical and immunological profile
      and oral colonization of Candida spp in HIV-infected patients with chronic
      periodontitis.
AB  - BACKGROUND: After the introduction of antiretroviral therapy (ART), human
      immunodeficiency virus (HIV) infection has become a chronic controllable disease.
      For this reason, chronic conditions related to both HIV infection and senescence,
      such as chronic periodontitis (CP) need to be studied. This study investigated
      the impact of non-surgical periodontal therapy (NSPT) on clinical and
      immunological features of CP, and on oral colonization by Candida spp. in HIV
      infected and non-HIV-infected individuals. METHODS: HIV-infected (test group) and
      non-HIV-infected (control group) adults patients with CP were selected. Gingival
      bleeding index (GI), probing depth (PD), clinical attachment level (CAL), number
      of teeth, CD4+ T lymphocytes and viral load (only for HIV-infected individuals),
      salivary cytokines (interleukin, [IL]-6, IL-8, and tumoral necrosis factor-alpha
      [TNF-alpha]), and oral Candida infection (colony forming units and species) were
      assessed at baseline, and 30 and 90 days after NSPT. RESULTS: Twenty-two HIV
      infected patients and 20 non-HIV-infected patients were evaluated. Candida counts
      and salivary IL-6, IL-8, and TNF-a levels were higher in the test group than in
      the control group. Both groups showed a decrease in oral Candida counts, GI, PD,
      IL-6, and IL-8 as well as gain in CAL at 30 and 90 days after NSPT. In addition,
      patients in the test group showed an increase of CD4+ T lymphocytes and a
      decrease of viral load. CONCLUSION: NSPT had a beneficial impact on clinical and
      immunological parameters of CP, reduction of oral Candida counts, and improvement
      of HIV-infection status.

PMID- 30118538
TI  - Diagnosis of gestational diabetes: a 'teachable moment'.
AB  - AIMS: Research regarding the determinants of concordance with gestational
      diabetes mellitus (GDM) treatment is limited. Here, we test whether the
      psychosocial changes outlined in the teachable moments model, as proposed by
      McBride et al. (McBride CM, Emmons KM, Lipkus IM. Understanding the potential of
      teachable moments: the case of smoking cessation. Health Educ Res 2003; 18: 156
      170) are associated with following GDM treatment recommendations. METHODS: Fifty
      nine women completed a baseline questionnaire (1 week after GDM diagnosis) in
      which they reported risk perception, social support, emotional response, the
      importance of their maternal identity and self-efficacy. One month later,
      participants reported their concordance with instructions regarding glucose
      monitoring, diet and, if applicable, medication. We used regression analysis to
      test for associations between the psychosocial factors measured at baseline and
      concordance at 1-month follow-up. RESULTS: Those who perceived their risk as
      higher or felt supported by family or friends were more likely to report a high
      level of concordance with GDM treatment. Emotional response, identity salience
      and self-efficacy were not related to concordance. CONCLUSIONS: Future
      interventions designed to increase concordance could benefit from a focus on risk
      perception and social support, as these factors appear to be most strongly
      associated with following GDM treatment recommendations.

PMID- 30118539
TI  - Distinguishing Characteristics of Robotic Writing.
AB  - Advances in robotic handwriting technology create new challenges for forensic
      document examiners. In the past, devices such as the autopen were used to
      replicate signatures of government officials and corporate companies. In today's
      technology, companies such as Bond utilize robots to create written documents,
      which mimic natural patterns of handwriting. They generate customizable written
      samples by simulating pen movements and letter formations. Four forensic document
      examiners were given various reproduced questioned documents and utilized a
      modified ACE-V (analysis, comparison, evaluation, verification) methodology to
      determine their genuineness. Examiners were able to make a distinction between
      the human writing samples and the skilled robotic equivalents. Several distinct
      features that are not seen in natural handwriting, such as even pen pressure and
      the superimposition of letterforms were observed in the robotic samples. Careful
      examination of identifying features of the Bond produced documents resulted in an
      opinion of nongenuineness.

PMID- 30118540
TI  - Seroprevalence of West Nile and dengue virus in the human population of the
      Bolivian Chaco.
AB  - To determine the seroprevalence of antibodies against dengue virus (DENV) and
      West Nile virus (WNV) in the human population of the Bolivian Chaco, we tested
      256 inhabitants of two rural communities. The seroprevalence, confirmed by plaque
      reduction neutralization test, was 7.8% and 2.7% for DENV and WNV, respectively.

PMID- 30118541
TI  - Polymeric Graphene Bulk Materials with a 3D Cross-Linked Monolithic Graphene
      Network.
AB  - Although many great potential applications are proposed for graphene, till now
      none are yet realized as a stellar application. The most challenging issue for
      such practical applications is to figure out how to prepare graphene bulk
      materials while maintaining the unique two-dimensional (2D) structure and the
      many excellent properties of graphene sheets. Herein, such polymeric graphene
      bulk materials containing three-dimensional (3D) cross-linked networks with
      graphene sheets as the building unit are reviewed. The theoretical research on
      various proposed structures of graphene bulk materials is summarized first. Then,
      the synthesis or fabrication of these graphene materials is described, which
      comprises mainly two approaches: chemical vapor deposition and cross-linking
      using graphene oxide directly. Finally, some exotic and exciting potential
      applications of these graphene bulk materials are presented.

PMID- 30118542
TI  - Lipoxin A4 ameliorates renal ischaemia-reperfusion-induced acute lung injury in
      rats.
AB  - Lipoxin A4 (LA4), a bioactive product of arachidonic acid, has been shown to
      exert strong anti-inflammatory activity. By contrast, the anti-inflammatory
      action of LA4 in a renal ischaemia-reperfusion (RIR)-mediated acute lung
      inflammation (ALI) model and the potential pathogenesis of the condition is still
      unclear. The aim of the current research was to investigate the effect of LA4 on
      RIR-induced ALI. The rat ALI model was induced by RIR. LA4 was injected via the
      tail vein immediately after RIR. The results indicate that LA4 markedly inhibits
      inflammatory cells infiltration, attenuates myeloperoxidase activity, and reduces
      the concentration of inflammatory mediators and Toll-like receptor 4 (TLR4) in
      RIR-induced ALI. Furthermore, LA4 suppressed nuclear factor kappa B (NF-kappaB)
      p65 and mitogen-activated protein kinase (MAPK) activation. The protective effect
      of LA4 in RIR-stimulated ALI was reversed by BOC-2 (an antagonist of the LA4
      receptor). These results indicate that LA4 exerts powerful anti-inflammatory
      functions in RIR-induced ALI by attenuating TLR4 expression via MAPK and NF
      kappaB signalling. Accordingly, LA4 might be an underlying treatment drug for RIR
      induced ALI.

PMID- 30118543
TI  - Electroluminescent Devices Based on 2D Semiconducting Transition Metal
      Dichalcogenides.
AB  - Ultrathin layers of van der Waals inorganic semiconductors represent a new class
      of excitonic materials with attractive light-emitting properties. Recent
      observation of valley polarization, optically pumped lasing, exciton-polaritons,
      and single-photon emission highlights the exciting prospects for two-dimensional
      (2D) semiconductors for applications in novel photonic devices. Development of
      efficient and reliable light sources based on excitonic electroluminescence in 2D
      semiconductors is of fundamental importance toward the practical implementation
      of photonic devices. Achieving electroluminescence in these atomically thin
      layers requires unconventional device designs and in-depth understanding of the
      carrier injection and transport mechanisms. Herein, various strategies for
      electrically generating excitons in 2D semiconducting transition metal
      dichalcogenides such as monolayer MoS2 are reviewed and challenges and
      opportunities are outlined. Furthermore, novel device concepts such as tunable
      chiral emission, electrically driven quantum emission, and high-frequency
      modulation are highlighted.

PMID- 30118544
TI  - 1 H and 13 C NMR assignments for (N-Methyl)-(-)-(alpha)-isosparteinium iodide and
      (N-Methyl)-(-)-sparteinium iodide.

PMID- 30118545
TI  - Synthesis of deuterium-labeled crizotinib, a potent and selective dual inhibitor
      of mesenchymal-epithelial transition factor (c-MET) kinase and anaplastic
      lymphoma kinase (ALK).
AB  - To more accurately and rapidly achieve quantitative detection of clinical
      crizotinib samples, stable isotope labeled crizotinib was required as an internal
      standard. We have developed a method to prepare racemic [D9 ] crizotinib using a
      base-catalyzed H/D exchange of both nitroso compound 2 and the acetophenone
      compound 6 with D2 O and NaBD4 reduction of 7 as the key steps to introduce the 9
      deuterium atoms. Starting with 4-hydroxypiperidine, 14-step synthesis furnished
      the desired racemic [D9 ] crizotinib 18. The deuterium-labeled compound 18 with
      the chemical purity of 99.62% was applicable for use as internal standards in the
      drug clinical study.

PMID- 30118546
TI  - Cocaine withdrawal reduces GABAB R transmission at entopeduncular nucleus -
      lateral habenula synapses.
AB  - Lateral habenula (LHb) hyperactivity plays a pivotal role in the emergence of
      negative emotional states, including those occurring during withdrawal from
      addictive drugs. We have previously implicated cocaine-driven adaptations at
      synapses from the entopeduncular nucleus (EPN) to the LHb in this process.
      Specifically, ionotropic GABAA receptor (R)-mediated neurotransmission at EPN-to
      LHb synapses is reduced during cocaine withdrawal, due to impaired vesicle
      filling. Recent studies have shown that metabotropic GABAB R signaling also
      controls LHb activity, although its role at EPN-to-LHb synapses during drug
      withdrawal is unknown. Here, we predicted that cocaine treatment would reduce
      GABAB R-mediated neurotransmission at EPN-to-LHb synapses. We chronically treated
      mice with saline or cocaine, prepared brain slices after two days of withdrawal
      and performed voltage-clamp recordings from LHb neurons whilst optogenetically
      stimulating EPN terminals. Compared with controls, mice in cocaine withdrawal
      exhibited reduced GABAA R-mediated input to LHb neurons, and a reduced occurrence
      of GABAB R-signaling at EPN-to-LHb synapses. We then assessed the underlying
      mechanism of this decrease. Application of GABAB R agonist baclofen evoked
      similar postsynaptic responses in EPN-innervated LHb neurons in saline- and
      cocaine-treated mice. Release probability at EPN-to-LHb GABAergic synapses was
      also comparable between groups. However, incubating brain slices in glutamine to
      facilitate GABA vesicle filling, normalized GABAB R-currents at EPN-to-LHb
      synapses in cocaine-treated mice. Overall, we show that during cocaine
      withdrawal, together with reduced GABAA R transmission, also GABAB R-mediated
      inhibitory signaling is diminished at EPN-to-LHb synapses, likely via the same
      presynaptic deficit. In concert, these alterations are predicted to contribute to
      the emergence of drug withdrawal symptoms, facilitating drug relapse.

PMID- 30118547
TI  - Quantum-Sized Metal Catalysts for Hot-Electron-Driven Chemical Transformation.
AB  - Hot-electron-driven chemical transformation (HEDCT) represents an emerging
      research area in utilizing photoresponsive nanoparticles to enable efficient
      solar-to-chemical conversion. The unique properties of quantum-sized metal
      nanoparticles (QSMNPs) make them a class of photocatalysts that can generate hot
      electrons to drive surface chemical reactions with high quantum efficiency.
      Compared to the conventional thermal-driven chemical reactions, HEDCT offers the
      advantages of accelerating reaction rate, improving reaction selectivity, and
      possibly enabling the occurrence of thermodynamically endergonic reactions.
      Despite its embryonic stage of development, using QSMNPs for HEDCT shows great
      promise. Herein, a timely overview on the research progress is provided with a
      focus on the fundamental quantum processes involved in the photoexcitation of hot
      electrons and the following HEDCT on the surface of QSMNPs. The last section
      discusses the challenges, which also represent the opportunities for the
      materials research community, in designing robust QSMNP photocatalysts and
      understanding the fundamental quantum phenomena in HEDCT.

PMID- 30118548
TI  - Parts-per-Million-Level Doping Effects in Organic Semiconductor Films and Organic
      Single Crystals.
AB  - Controlling the pn-type behavior of a semiconductor such as silicon by adding an
      extremely small quantity of an impurity (doping) is a central part of inorganic
      semiconductor electronics since the 20th century. Recent progress in the doping
      of organic semiconductors strongly suggests the advent of a new era of doped
      organic semiconductors. Here, the principles and effects of doping at the level
      of parts per million (ppm) in organic semiconductor films and single crystals are
      described, including descriptions of complete pn-control, doping sensitization,
      ppm doping using an extremely low-speed deposition technique reaching 10-9 nm s-1
      , and emerging ppm-level doping effects, such as trap filling, majority carriers,
      homojunction formation, and decreased mobility, as well as ppm-level doping
      effects in organic single crystals measured by the Hall effect, which shows a
      doping efficiency of 24%. The Wannier excitonic doping of organic single crystals
      possessing band conduction and the defect science of organic single crystals
      related to carrier trapping and scattering are introduced as a new scientific
      field. The dawn of organic single-crystal electronics is also discussed.

PMID- 30118549
TI  - Manganese-Oxide-Based Electrode Materials for Energy Storage Applications: How
      Close Are We to the Theoretical Capacitance?
AB  - Of the transition metals, Mn has the greatest number of different oxides, most of
      which have a special tunnel structure that enables bulk redox reactions. The high
      theoretical capacitance and capacity results from a greater number of accessible
      oxidation states than other transition metals, wide potential window, and the
      high natural abundance make MnOx species promising electrode materials for energy
      storage applications. Although MnOx electrode materials have been intensely
      studied over the past decade, their electrochemical performance is still
      insufficient for practical applications. Currently, there is a trade-off between
      specific capacitance and loading mass. MnOx species have intrinsically poor
      electrical conductivity, and current structural designs are not sophisticated
      enough to accommodate enough redox-active sites. Recent studies have certainly
      made progress in increasing capacitance through making use of electrically
      conductive components and controlling the morphology of the MnOx species to
      expose more surface area. To increase the capacitance of MnOx electrodes to the
      largest extent without limiting loading mass, further structural design at the
      nanoscale and manipulation of the electrically conductive component are required.
      An ideal nanostructure is proposed to guide future research toward closing the
      gap between achieved and theoretical capacitance, without limiting the loading
      mass.

PMID- 30118550
TI  - Redox-Targeting-Based Flow Batteries for Large-Scale Energy Storage.
AB  - Redox-targeting reactions of battery materials by redox molecules are extensively
      studied for energy storage since the first report in 2006. Implementation of the
      "redox-targeting" concept in redox flow batteries presents not only an innovative
      idea of battery design that considerably boosts the energy density of flow
      battery system, but also an intriguing research platform applied to a wide
      variety of chemistries for different applications. Here, a critical overview of
      the recent progress in redox-targeting-based flow batteries is presented and the
      development of the technology in the various aspects from mechanistic
      understanding of the reaction kinetics to system optimization is highlighted. The
      limitations presently lying ahead for the widespread applications of "redox
      targeting" are also identified and recommendations for addressing the constraints
      are given. The adequate development of the redox-targeting concept should provide
      a credible solution for advanced large-scale energy storage in the near future.

PMID- 30118551
TI  - Additional factors to consider while providing humidification support to
      neonates.

PMID- 30118552
TI  - Performances of creatinine-based glomerular filtration rate estimating equations
      in simultaneous pancreas-kidney transplant recipients: a single center cohort
      study.
AB  - Estimating glomerular filtration rate (GFR) is important for clinical management
      and research studies in simultaneous pancreas-kidney transplantation (SPK)
      recipients. No study has specifically investigated the reliability of recent
      creatinine-based GFR estimating equations in this singular population. We
      assessed the performances of CKD-EPI, MDRD, Schwartz-2009, Schwartz-Lyon, Lund
      Malmo and Full Age Spectrum equations for estimating GFR after SPK. 126 patients
      were included. GFR was measured by a reference method (mGFR) one year after SPK
      and estimated with the different equations from a standardized measure of serum
      creatinine. Relative bias, precisions, 10% and 30% accuracies (P30) were used to
      determine equations reliability. Ages ranged from 29 to 58. Mean mGFR was 56.3 +/
      13.3 [23.6-92.5] ml/min/1.73 m2 . In the whole population, P30 of the CKD-EPI
      and MDRD equations were 42% (38.0; 46.0) and 65% (61.5; 69) respectively. As
      compared to the other equations, the Schwartz-Lyon equation was significantly
      more accurate (P30 = 86.0% [83.5-88.0], P < 0.01) and less biased (1.13 [1.06
      1.19], P < 0.01). Conclusions were similar whatever the age class (<40 or >=40)
      and mGFR level (<60 or >=60 ml/min/1.73 m2 ). This study suggests that the CKD
      EPI and MDRD equations have poor performances in SPK recipients and that the
      Schwartz-Lyon equation is a reliable alternative.

PMID- 30118553
TI  - Understanding the epidemiological characteristics of EV71 and CVA16 infection to
      aid the diagnosis and treatment of hand, foot, and mouth disease.
AB  - Hand, foot, and mouth disease (HFMD) have been recognized over the past several
      years as a highly infectious disease in children. Enterovirus 71 (EV71) and
      coxsackievirus A16 (CVA16) are the two major causative agents. The objective of
      this study was to determine the optimal time and method of HFMD detection,
      explore the seroconversion of IgM and IgG antibodies, and examine the response of
      neutralizing antibody (NtAb) to EV71 or CVA16. Between January 2016 and December
      2017, a total of 460 patients, diagnosed with HFMD based on clinical symptoms and
      hospitalized in the First Hospital of Jilin University, were recruited for the
      study. At approximately 72 hours post illness onset, we observed that the
      positive rate of both IgM and real-time polymerase chain reaction detection of
      EV71 or CVA16 was the highest, this could be considered as the optimal detection
      time for clinical diagnosis. During the initial 0 -96 hours, the relative highest
      IgM and the relative lowest IgG antibody levels were observed. The NtAb titers to
      EV71 and CVA16 also gradually increased with time, showing a positive correlation
      with age, and being the predominant factor during the hospitalized days. Thus,
      our study provides important information for the clinical diagnosis and treatment
      of HFMD.

PMID- 30118555
TI  - Monitoring of hydrogenation by benchtop NMR with parahydrogen-induced
      polarization.

PMID- 30118554
TI  - Reply to "Ex situ normothermic machine perfusion of donor livers using a
      haemoglobin-based oxygen carrier: a viable alternative to red blood cells".

PMID- 30118556
TI  - Aberrant DNA methylation profile of hepatitis B virus infection.
AB  - We aimed to study the aberrant DNA methylation profile associated with hepatitis
      B virus (HBV) infection and, to identify key genes and pathways associated with
      the HBV infection stage. A total of 54 antiviral treatment-naive HBV-infected
      patients and six healthy controls were included. Genome-wide methylated DNA
      immunoprecipitation analysis was performed, as previously described, after which
      the chip data were preprocessed. Subsequently, Cytoscape software was used for
      the construction of a protein-protein interaction network, and a database for
      annotation, visualization, and integrated discovery software was used to conduct
      functional enrichment analysis. A total of 711 794 CpGs were obtained after data
      quality control, among which 152 780, 113 814, 90 747, and 175 868 CpGs showed
      differential methylation in acute hepatitis B (AHB) vs control, total-C vs
      control, CH1 vs CA1, and AHB vs total-C, respectively. Furthermore, RIPK3,
      PRDM10, JUN, and SNAI1 were at the center of the four associated networks,
      respectively. Differential methylated genes differentially methylated in these
      four comparisons were significantly enriched with olfactory transduction;
      positive regulation of transport; negative regulation of protein amino acid
      phosphorylation (eg, JUN), phosphorylation, phosphorus metabolic process, and
      phosphate metabolic process; and programmed cell death, respectively. RIPK3,
      PRDM10, JUN, and SNAI1 as well as olfactory transduction, positive regulation of
      transport, negative regulation of phosphorylation, and programmed cell death are
      important for the transformation associated with HBV infection stage. Moreover,
      JUN may be involved in HBV infection, mainly via the negative regulation of amino
      acid phosphorylation.

PMID- 30118557
TI  - Parent-child communication and timing of interventions are challenges in the
      Duchenne muscular dystrophy care.
AB  - AIM: Duchenne muscular dystrophy (DMD) is an X-linked myopathy affecting one in
      3600-6000 live male births. The aim of this study was to gain further insight
      into how parents experience caring for boys with DMD. METHODS: Using a
      qualitative design, parents in 12 families with boys with DMD, whereof two pairs
      of siblings, were interviewed in 2014 and 2015. Participants were parents of boys
      followed at Oslo University Hospital or other hospitals in the south-eastern
      health region of Norway. Mean age of the boys was 13 years, range 7-17. RESULTS:
      Parents expressed the importance of obtaining good information about the
      diagnosis, supplied with sensitivity for them as clients, and the parents must be
      involved in timing of interventions. Meeting with others in the same situation
      was highly appreciated. Many of the parents expressed their own need for support
      to cope with the difficult situation. Continuity of support in the boys'
      transition to adulthood was pointed out as important, as well as the need for
      professional help to talk to the boys about their diagnosis. CONCLUSION: Our
      study suggests that professional teams should expand the parental perspective and
      emphasise a holistic approach in their work with patients with DMD.

PMID- 30118558
TI  - The Rise of Hydrogen Peroxide as the Main Product by Metal-Free Catalysis in
      Oxygen Reductions.
AB  - One of the recent trends in electrocatalytic reactions involves the oxygen
      reduction reaction (ORR), where a new paradigm has been shaped to exploit this
      reaction for the synthesis of hydrogen peroxide (H2 O2 ). H2 O2 is a very
      versatile chemical of high commercial value, prepared currently through poorly
      sustainable processes. The emergence of metal-free carbon catalysts for the
      selective synthesis of H2 O2 is expected to revolutionize ORR research, beckoning
      at the development of new industrial schemes. The complexities of the mechanism
      and the factors dominating the selectivity of the process have been unveiled
      through a combination of theoretical and experimental studies.

PMID- 30118559
TI  - Engineering Functional Metal Materials at the Atomic Level.
AB  - With continuous research efforts devoted into synthesis and characterization
      chemistry of functional nanomaterials in the past decades, the development of
      metal materials is stepping into a new era, where atom-by-atom customization of
      property-dictating structural attributes is expected. Herein, the state-of-the
      art modulation of functional metal nanomaterials at the atomic level, by size-
      and structure-controlled synthesis of thiolate-protected metal (e.g., Au and Ag)
      nanoclusters (NCs), is exemplified. Metal NCs are ultrasmall (<3 nm) particles
      with hierarchical primary, secondary, and tertiary structures, reminiscent of
      natural proteins or enzymes. Given the proven dependence of their physicochemical
      properties on their size and structure, documented synthetic methodologies
      delivering NCs with atomic-level monodispersity and tailorable size and
      structural attributes at individual hierarchical levels are categorized and
      discussed. Such assured atomic-level modulation could confer metal NCs with novel
      application opportunities in diverse fields, which are also exemplified by their
      size- and structure-dictated catalytic and biomedical performance. The precise
      synthesis and application chemistry developed based on the hierarchical structure
      scheme of metal NCs could increase the acceptance of metal NCs as a new family of
      functional materials.

PMID- 30118560
TI  - Optical analysis of functional development of the facial motor nucleus in the
      embryonic rat brainstem.
AB  - Facial motor neurons of the rat embryo are first generated in rhombomere 4 and
      then migrate in the caudo-ventral direction. This migration forms a unique axonal
      trajectory called the genu, a loop of facial motor axons around the abducens
      nucleus. It is still unclear when and how this unique structure is functionally
      established during ontogenesis. Using voltage-sensitive dye (VSD) recording and
      the DiI staining method, we identified neural responses evoked by facial nerve
      (N.VII) stimulation and examined developmental processes of the facial motor
      nucleus in E12-E17 rat brainstems. We identified two types of fast spike-like
      signals; a long-duration signal, which corresponded to the action potential in
      the N.VII soma, and a short-duration signal, which reflected the action potential
      in the N.VII axons. The long-duration signal was detected as early as E13,
      suggesting that the N.VII motor neuron is already excitable at the beginning of
      cell migration. The response area of the long-duration signal extended caudally
      at E13-E14, and shifted in a ventral direction at E15. At E16-E17, the long
      duration signal was concentrated in the caudo-ventral area, which was comparable
      to the location of the facial motor nucleus in the adult rat brainstem. These
      results demonstrate that developmental processes of cell migration and nuclear
      organization can be visualized and identified functionally with the VSD
      recording. We discuss the results by comparing functiogenesis and morphogenesis
      of the N.VII pathway.

PMID- 30118562
TI  - Polyprodrug Antimicrobials: Remarkable Membrane Damage and Concurrent Drug
      Release to Combat Antibiotic Resistance of Methicillin-Resistant Staphylococcus
      aureus.
AB  - The increased threat of antibiotic resistance has created an urgent need for new
      strategies. Herein, polyprodrug antimicrobials are proposed to mimic
      antimicrobial peptides appended with a concurrent drug release property,
      exhibiting broad-spectrum antibacterial activity and especially high potency to
      inhibit methicillin-resistant Staphylococcus aureus (MRSA) without inducing
      resistance. Two series of polyprodrug antimicrobials are fabricated by facile
      polymerization of triclosan prodrug monomer (TMA) and subsequent quaternization
      of hydrophilic poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA), affording
      PDMAEMA-b-PTMA and PQDMA-b-PTMA, respectively. Optimized samples with proper
      hydrophobic ratio are screened out, which exhibit remarkable bacterial inhibition
      and low hemolysis toward red blood cells. Furthermore, synergistic antibacterial
      mechanisms contribute to the bacteria killing, including serious membrane damage,
      increased out-diffusion of cytosolic milieu across the membrane, and
      intracellular reductive milieu-mediated triclosan release. No detectable
      resistance is observed for polyprodrug antimicrobials against MRSA, which is
      demonstrated to be better than commercial triclosan and vancomycin against in
      vivo MRSA-infected burn models and a promising approach to the hurdle of
      antibiotic resistance in biomedicine.

PMID- 30118561
TI  - Cocaine self-administration is increased after frontal traumatic brain injury and
      associated with neuroinflammation.
AB  - Traumatic brain injury (TBI) has been linked to the development of numerous
      psychiatric diseases, including substance use disorder. However, it can be
      difficult to ascertain from clinical data whether the TBI is cause or consequence
      of increased addiction vulnerability. Surprisingly few studies have taken
      advantage of animal models to investigate the causal nature of this relationship.
      In terms of a plausible neurobiological mechanism through which TBI could magnify
      the risk of substance dependence, numerous studies indicate that TBI can cause
      widespread disruption to monoaminergic signaling in striatal regions, and also
      increases neuroinflammation. In the current study, male Long-Evans rats received
      either a mild or severe TBI centered over the frontal cortex via controlled
      cortical impact, and were subsequently trained to self-administer cocaine over 10
      6-hour sessions. At the end of the study, markers of striatal dopaminergic
      function, and levels of inflammatory cytokine levels in the frontal lobes, were
      assessed via western blot and multiplex ELISA, respectively. There was
      significantly higher cocaine intake in a subset of animals with either mild or
      severe TBI. However, many animals within both TBI groups failed to acquire self
      administration. Principal components analysis suggested that both dopaminergic
      and neuroinflammatory proteins were associated with overall cocaine intake, yet
      only an inflammatory component was associated with acquisition of self
      administration, suggesting neuroinflammation may make a more substantial
      contribution to the likelihood of drug-taking. Should neuroinflammation play a
      causal role in mediating TBI-induced addiction risk, anti-inflammatory therapy
      may reduce the likelihood of substance abuse in TBI populations.

PMID- 30118563
TI  - Coadministration of Probiotics With Prescribed Antibiotics for Preventing
      Clostridium difficile Diarrhea.

PMID- 30118564
TI  - Thylakoid proteome modulation in pea plants grown at different irradiances:
      quantitative proteomic profiling in a non-model organism aided by transcriptomic
      data integration.
AB  - Plant thylakoid membranes contain hundreds of proteins that closely interact to
      cope with ever-changing environmental conditions. We investigated how Pisum
      sativum L. (pea) grown at different irradiances optimizes light-use efficiency
      through the differential accumulation of thylakoid proteins. Thylakoid membranes
      from plants grown under low (LL), moderate (ML) and high (HL) light intensity
      were characterized by combining chlorophyll fluorescence measurements with
      quantitative label-free proteomic analysis. Protein sequences retrieved from
      available transcriptomic data considerably improved thylakoid proteome profiling,
      increasing the quantifiable proteins from 63 to 194. The experimental approach
      used also demonstrates that this integrative omics strategy is powerful for
      unravelling protein isoforms and functions that are still unknown in non-model
      organisms. We found that the different growth irradiances affect the electron
      transport kinetics but not the relative abundance of photosystems (PS) I and II.
      Two acclimation strategies were evident. The behaviour of plants acclimated to LL
      was compared at higher irradiances: (i) in ML, plants turn on photoprotective
      responses mostly modulating the PSII light-harvesting capacity, either
      accumulating Lhcb4.3 or favouring the xanthophyll cycle; (ii) in HL, plants
      reduce the pool of light-harvesting complex II and enhance the PSII repair cycle.
      When growing at ML and HL, plants accumulate ATP synthase, boosting both cyclic
      and linear electron transport by finely tuning the DeltapH across the membrane
      and optimizing protein trafficking by adjusting the thylakoid architecture. Our
      results provide a quantitative snapshot of how plants coordinate light
      harvesting, electron transport and protein synthesis by adjusting the thylakoid
      membrane proteome in a light-dependent manner.

PMID- 30118565
TI  - Sleep quality and its association with the insular cortex in emotional empathy.
AB  - The human ability to vicariously share someone else's emotions (i.e., emotional
      empathy) relies on an extended neural network including regions in the anterior
      cingulate and insular cortex. Here, we tested the hypothesis that good sleep
      quality is associated with increased activation in the brain areas underlying
      emotional empathy. To this aim, we assessed subjective sleep quality in a large
      sample of healthy young volunteers, and asked participants to complete a
      computerized emotional empathy task. Then, we asked 16 participants to complete
      the same task while undergoing functional Magnetic Resonance Imaging (fMRI).
      After confirming the behavioral relationship between quality of sleep and
      emotional empathy in the large sample, we conducted a Region of Interest (ROI)
      analysis on selected ROIs involved in emotional empathy, and measured Blood
      Oxygen Level Dependent (BOLD) signal change in participants who performed the
      emotional empathy task in the MRI scanner; additionally, we assessed how the BOLD
      signal in different brain areas temporally correlated with performance throughout
      the task (i.e., task-based functional connectivity). We found increased BOLD
      signal change in a selective region within the left insula for individuals with
      better subjective sleep quality. These findings provide the very first evidence
      that individuals' sleep quality relates to emotional empathic responses through
      increased neural activation of a specific area within the insular cortex.

PMID- 30118566
TI  - TBL10 is required for O-acetylation of pectic rhamnogalacturonan-I in Arabidopsis
      thaliana.
AB  - O-Acetylated pectins are abundant in the primary cell wall of plants and growing
      evidence suggests they have important roles in plant cell growth and interaction
      with the environment. Despite their importance, genes required for O-acetylation
      of pectins are still largely unknown. In this study, we showed that TRICHOME
      BIREFRINGENCE LIKE 10 (AT3G06080) is involved in O-acetylation of pectins in
      Arabidopsis (Arabidopsis thaliana). The activity of the TBL10 promoter was strong
      in tissues where pectins are highly abundant (e.g. leaves). Two homozygous knock
      out mutants of Arabidopsis, tbl10-1 and tbl10-2, were isolated and shown to
      exhibit reduced levels of wall-bound acetyl esters, equivalent of ~50% of the
      wild-type level in pectin-enriched fractions derived from leaves. Further
      fractionation revealed that the degree of acetylation of the pectin
      rhamnogalacturonan-I (RG-I) was reduced in the tbl10 mutant compared to the wild
      type, whereas the pectin homogalacturonan (HG) was unaffected. The degrees of
      acetylation in hemicelluloses (i.e. xyloglucan, xylan and mannan) were
      indistinguishable between the tbl10 mutants and the wild type. The mutant plants
      contained normal trichomes in leaves and exhibited a similar level of
      susceptibility to the phytopathogenic microorganisms Pseudomonas syringae pv.
      tomato DC3000 and Botrytis cinerea; while they displayed enhanced tolerance to
      drought. These results indicate that TBL10 is required for O-acetylation of RG-I,
      possibly as an acetyltransferase, and suggest that O-acetylated RG-I plays a role
      in abiotic stress responses in Arabidopsis.

PMID- 30118567
TI  - Insertion of a transposon-like sequence in the 5'-flanking region of the YUCCA
      gene causes the stony hard phenotype.
AB  - Melting-flesh peaches produce large amounts of ethylene, resulting in rapid fruit
      softening at the late-ripening stage. In contrast, stony hard peaches do not
      soften and produce little ethylene. The indole-3-acetic acid (IAA) level in stony
      hard peaches is low at the late-ripening stage, resulting in low ethylene
      production and inhibition of fruit softening. To elucidate the mechanism of low
      IAA concentration in stony hard peaches, endogenous levels of IAA and IAA
      intermediates or metabolites were analysed by ultra-performance liquid
      chromatography-tandem mass spectrometry. Although the IAA level was low, the
      indole-3-pyruvic acid (IPyA) level was high in stony hard peaches at the ripening
      stage. These results indicate that YUCCA activity is reduced in ripening stony
      hard peaches. The expression of one of the YUCCA isogenes in peach, PpYUC11, was
      suppressed in ripening stony hard peaches. Furthermore, an insertion of a
      transposon-like sequence was found upstream of the PpYUC11 gene in the 5'
      flanking region. Analyses of the segregation ratio of the stony hard phenotype
      and genotype in F1 progenies indicated that the transposon-inserted allele of
      PpYUC11, hd-t, correlated with the stony hard phenotype. On the basis of the
      above findings, we propose that the IPyA pathway (YUCCA pathway) is the main
      auxin biosynthetic pathway in ripening peaches of 'Akatsuki' and 'Manami'
      cultivars. Because IAA is not supplied from storage forms, IAAde novo synthesis
      via the IPyA pathway (YUCCA pathway) in mesocarp tissues is responsible for auxin
      generation to support fruit softening, and its disruption can lead to the stony
      hard phenotype.

PMID- 30118568
TI  - Interactive Lecture in the Dissection Hall: Transforming Passive Lecture into a
      Dynamic Learning Experience.
AB  - Traditionally, cadaver dissection and didactic lectures have formed the mainstay
      of teaching gross anatomy, but, apathy of the learners toward didactic lectures
      and reduction in the time allotted for teaching anatomy have necessitated
      adoption of interactive teaching methods that require lesser student contact
      time. In this study, for two consecutive years, first-year medical students were
      taught selected gross anatomy topics using Interactive Lecture in the Dissection
      Hall (ILDH). Instead of discarding the traditional methods, ILDH combined the two
      into a single, cohesive, interactive session, to teach the topic through
      multiple, short, segments of lecture alternating with interactive demonstration
      on the specimen. This method emerged by combining the insight gained from the
      newer teaching methods and reasoning from the cognitive load theory and
      contiguity principle. Students' performance after ILDH was assessed by a test and
      was compared with the performance after conventional method of teaching.
      Students' perception toward ILDH was assessed by a questionnaire. Students
      perceived that ILDH not only helped them in understanding the concepts better
      (97.7%), but, was also a better learning experience (99.2%). Majority felt that
      ILDH should be made an integral part of teaching anatomy (97.7%). Students'
      performance in the test after the unified approach of ILDH was significantly
      better than with the split-source format of conventional methods. Students'
      satisfaction, improved scores, and time efficiency indicate that ILDH may be an
      optimum method for teaching selected topics in anatomy.

PMID- 30118569
TI  - Regenerative surgical treatment of peri-implantitis using either a collagen
      membrane or concentrated growth factor: A 12-month randomized clinical trial.
AB  - BACKGROUND: Platelet concentration based membranes, as well as collagen membranes
      in combination with bone substitutes, have demonstrated successful outcomes in
      regeneration of peri-implant bone defects (PBD). PURPOSE: The aim of this study
      was to evaluate the clinical and radiographic outcomes of regenerative surgical
      treatment (RST) of peri-implantitis using a bone substitute combined with two
      different bioresorbable barrier membranes, either collagen membrane (CM) or
      concentrated growth factor (CGF), during 12-month follow-up. MATERIALS AND
      METHODS: Fifty two patients, who had at least one peri-implantitis lesion was
      treated by using a bone substitute in combination with CGF or CM. After surgical
      procedures, implants were allowed for submerged healing. Clinical assessments
      were conducted at baseline, 6 and 12 months postoperatively, while radiographic
      evaluation was performed at baseline and 12 months. RESULTS: Significant
      reductions were obtained in the mean gingival index (GI), bleeding on probing
      (BOP), probing depth (PD), clinical attachment level (CAL) and mucosal recession
      (MR) values at both 6 and 12 months postoperatively compared to baseline for both
      treatment procedures (P < 0.05). At 6 months, no statistically significant
      difference was observed for all clinical parameters between the groups, whereas
      the mean PD, CAL and vertical defect depth (VDD) values were statistically
      significant in favor of the CM group at 12 months (P < 0.05). The mean defect
      fill (DF) in the CM group (1.99 +/-0.76) was not statistically significantly
      different from that observed in the CCF group (1.63 +/-1.00) (P = 0.154).
      CONCLUSIONS: The outcomes of the present study suggest that both regenerative
      approaches yielded significant improvements in both clinical and radiographic
      assessments. The procedure using a collagen membrane in combination with a bone
      substitute showed better results at 12 months in RST of peri-implantitis.

PMID- 30118571
TI  - Clinical Case-Based Image Portfolios in Medical Histopathology.
AB  - This descriptive article describes the use of clinical case-based portfolios in
      histopathology teaching laboratories in conjunction with virtual microscopy not
      only to integrate histology and pathology disciplines for first and second year
      medical students but also to stimulate student engagement, promote self-directed
      and group-based learning and enhance student-to-student interaction in a
      structured manner. Portfolios consisted of PowerPoint files encompassing four to
      five clinical case studies relevant to the topics covered that week. Portfolios
      integrated study materials provided in the module-specific lectures, clinical
      skill lectures, and online interactive content. Two sets of portfolios,
      Individual and Group, were used. Individual Portfolios were completed by each
      student and uploaded prior to the laboratory session. Group Portfolios were
      completed by students working together in small groups during the laboratory
      session with minimal faculty assistance. The functional utility and acceptance of
      Individual and Group Portfolios among first- and second-year medical students was
      evaluated using electronic surveys and examination performances. Both first- and
      second-year students agreed that the use of portfolios in conjunction with
      virtual microscopy promoted understanding and encouraged discussion of the topics
      covered during the week and that group members worked well together and
      contributed to the completion of the portfolios. Performances on the Histology
      and Cell Biology and Pathology sections on the United States Medical Licensing
      Examination(r) (USMLE(r) ) remained consistent and in line with national
      averages. Overall, use of portfolios promoted peer teaching and contributed
      towards successful transition to the new system-based integrated curriculum with
      continued strong performance on the USMLE. Anat Sci Educ 00: 000-000. (c) 2018
      American Association of Anatomists.

PMID- 30118570
TI  - Building and Breaking Bonds via a Compact S-Propargyl-Cysteine to Chemically
      Control Enzymes and Modify Proteins.
AB  - Analogous to reversible post-translational protein modifications, the ability to
      attach and subsequently remove modifications on proteins would be valuable for
      protein and biological research. Although bioorthogonal functionalities have been
      developed to conjugate or cleave protein modifications, they are introduced into
      proteins on separate residues and often with bulky side chains, limiting their
      use to one type of control and primarily protein surface. Here we achieved dual
      control on one residue by genetically encoding S-propargyl-cysteine (SprC), which
      has bioorthogonal alkyne and propargyl groups in a compact structure, permitting
      usage in protein interior in addition to surface. We demonstrated its
      incorporation at the dimer interface of glutathione transferase for in vivo
      crosslinking via thiol-yne click chemistry, and at the active site of human
      rhinovirus 3C protease for masking and then turning on enzyme activity via Pd
      cleavage of SprC into Cys. In addition, we installed biotin onto EGFP via
      Sonogashira coupling of SprC and then tracelessly removed it via Pd cleavage.
      SprC is small in size, commercially available, nontoxic, and allows for bond
      building and breaking on a single residue. Genetically encoded SprC will be
      valuable for chemically controlling proteins with an essential Cys and for
      reversible protein modifications.

PMID- 30118573
TI  - Daily heliotropic movements assist gas exchange and productive responses in
      DREB1A soybean plants under drought stress in the greenhouse.
AB  - Drought stress is one of the most severe environmental constraints on plant
      production. Under environmental pressures, complex daily heliotropic adjustments
      of leaflet angles in soybean can help to reduce transpiration losses by
      diminishing light interception (paraheliotropism), increase diurnal carbon gain
      in sparse canopies and reduce carbon gain in dense canopies by solar tracking
      (diaheliotropism). The plant materials studied were cultivar BR 16 and its
      genetically engineered isoline P58, ectopically overexpressing AtDREB1A, which is
      involved in abiotic stress responses. We aimed to follow the movements of central
      and lateral leaflets in vegetative stages V7-V10 and reproductive stages R4-R5,
      integrating the reversible morphogenetic changes into an estimate of daily plant
      photosynthesis using three-dimensional modeling, and to analyze the production
      parameters of BR 16 and P58. The patterns of daily movements of central leaflets
      of BR 16 in V7-V10 and R4-R5 were similar, expressing fewer diaheliotropic
      movements under drought stress than under non-limiting water conditions. Daily
      heliotropic patterns of lateral leaflets in V7-V10 and R4-R5 showed more
      diaheliotropic movements in drought-stressed P58 plants than in those grown under
      non-limiting water conditions. Leaf area in R4-R5 was generally higher in P58
      than in BR 16. Drought significantly affected gas exchange and vegetative and
      reproductive architectural features. DREB1A could be involved in various
      responses to drought stress. Compared with the parental BR 16, P58 copes with
      drought through better compensation between diaheliotropic and paraheliotropic
      movements, finer tuning of water-use efficiency, a lower transpiration rate,
      higher leaf area and higher pod abortion to accomplish the maximum possible grain
      production under continued drought conditions.

PMID- 30118572
TI  - Chinese cropping systems are a net source of greenhouse gases despite soil carbon
      sequestration.
AB  - Soil carbon sequestration is being considered as a potential pathway to mitigate
      climate change. Cropland soils could provide a sink for carbon that can be
      modified by farming practices; however, they can also act as a source of
      greenhouse gases (GHG), including not only nitrous oxide (N2 O) and methane (CH4
      ), but also the upstream carbon dioxide (CO2 ) emissions associated with
      agronomic management. These latter emissions are also sometimes termed "hidden"
      or "embedded" CO2 . In this paper, we estimated the net GHG balance for Chinese
      cropping systems by considering the balance of soil carbon sequestration, N2 O
      and CH4 emissions, and the upstream CO2 emissions of agronomic management from a
      life cycle perspective during 2000-2017. Results showed that although soil
      organic carbon (SOC) increased by 23.2 +/- 8.6 Tg C per year, the soil N2 O and
      CH4 emissions plus upstream CO2 emissions arising from agronomic management added
      269.5 +/- 21.1 Tg C-eq per year to the atmosphere. These findings demonstrate
      that Chinese cropping systems are a net source of GHG emissions and that total
      GHG emissions are about 12 times larger than carbon uptake by soil sequestration.
      There were large variations between different cropping systems in the net GHG
      balance ranging from 328 to 7,567 kg C-eq ha-1  year-1 , but all systems act as a
      net GHG source to the atmosphere. The main sources of total GHG emissions are
      nitrogen fertilization (emissions during production and application), power use
      for irrigation, and soil N2 O and CH4 emissions. Optimizing agronomic management
      practices, especially fertilization, irrigation, plastic mulching, and crop
      residues to reduce total GHG emissions from the whole chain is urgently required
      in order to develop a low-carbon future for Chinese crop production.

PMID- 30118574
TI  - Fluorescence-based assay for accurate measurement of transcriptional activity in
      trypanosomatid parasites.
AB  - Trypanosomatid parasites are causative agents of neglected human diseases. Their
      lineage diverged early from the common eukaryotic ancestor, and they evolved
      singular mechanisms of gene expression that are crucial for their survival.
      Studies on unusual and essential molecular pathways lead to new drug targets. In
      this respect, assays to analyze transcriptional activity will provide useful
      information to identify essential and specific factors. However, the current
      methods are laborious and do not provide global and accurate measures. For this
      purpose, a previously reported radiolabeling in vitro nascent mRNA methodology
      was used to establish an alternative fluorescent-based assay that is able to
      precisely quantify nascent mRNA using both flow cytometry and a high-content
      image system. The method allowed accurate and global measurements in Trypanosoma
      brucei, a representative species of trypanosomatid parasites. We obtained data
      demonstrating that approximately 70% of parasites from a population under normal
      growth conditions displayed mRNA transcriptional activity, whilst the treatment
      with alpha-amanitin (75 ug/ml) inhibited the polymerase II activity. The
      adaptation of the method also allowed the analyses of the transcriptional
      activity during the cell cycle. Therefore, the methodology described herein
      contributes to obtaining precise measurements of transcriptional rates using
      multiparametric analysis. This alternative method can facilitate investigations
      of genetic and biochemical processes in trypanosome parasites and consequently
      provide additional information related to new treatment or prophylaxis strategies
      involving these important human parasites.

PMID- 30118576
TI  - Remote-Controlling Potassium Channels in Living Cells through Photothermal
      Inactivation of Calmodulin.
AB  - Spatiotemporal regulation of cellular functions provides a powerful strategy for
      understanding underlying mechanisms of cellular bioprocesses. Here, a strategy is
      reported to realize the remote control of the activities of potassium channels
      via photothermal inactivation of calmodulin (CaM) by using reduced graphene oxide
      decorated with calmodulin binding peptide (rGO-P) as the transducer with near
      infrared light (NIR) irradiation. Upon NIR light irradiation, the CaM/Ca2+ bound
      to rGO-P is inactivated by the photothermal effect of rGO-P, resulting in the
      incapability of binding with Ca2+ . Hence, the closed Kv10.1 channel is converted
      to be open in the presence of calcium in living cells. Meanwhile, the SK2 channel
      is induced to be closed from the open state and the Kir2.1 channel is unaffected
      by the intracellular inactivation of CaM. This strategy gives a noninvasive and
      effective approach to remotely control the activities of potassium channels,
      offering an alternative for the development of optogenetics.

PMID- 30118575
TI  - Difficulty scoring system in laparoscopic distal pancreatectomy.
AB  - BACKGROUND: Several factors affect the level of difficulty of laparoscopic distal
      pancreatectomy (LDP). The purpose of this study was to develop a difficulty
      scoring (DS) system to quantify the degree of difficulty in LDP. METHODS: We
      collected clinical data for 80 patients who underwent LDP. A 10-level difficulty
      index was developed and subcategorized into a three-level difficulty index; 1-3
      as low, 4-6 as intermediate, and 7-10 as high index. The automatic linear
      modeling (LINEAR) statistical tool was used to identify factors that
      significantly increase level of difficulty in LDP. RESULTS: The operator's 10
      level DS concordance between the 10-level DS by the reviewers, LINEAR index DS,
      and clinical index DS systems were analyzed, and the weighted Cohen's kappa
      statistic were at 0.869, 0.729, and 0.648, respectively, showing good to
      excellent inter-rater agreement. We identified five factors significantly
      affecting level of difficulty in LDP; type of operation, resection line,
      proximity of tumor to major vessel, tumor extension to peripancreatic tissue, and
      left-sided portal hypertension/splenomegaly. CONCLUSIONS: This novel DS for LDP
      adequately quantified the degree of difficulty, and can be useful for selecting
      patients for LDP, in conjunction with fitness for surgery and prognosis.

PMID- 30118577
TI  - Adipose-derived stem cells and the stromal vascular fraction in polyglycolic acid
      collagen nerve conduits promote rat facial nerve regeneration.
AB  - Adipose-derived stem cells (ADSCs) and the stromal vascular fraction (SVF)
      promote nerve regeneration. Biodegradable nerve conduits are used to treat
      peripheral nerve injuries, but their efficiencies are lower than those of
      autologous nerve grafts. This study developed biodegradable nerve conduits
      containing ADSCs and SVF and evaluated their facial nerve regenerating abilities
      in a rat model with a 7-mm nerve defect. SVF and ADSCs were individually poured
      into nerve conduits with polyglycolic acid-type I collagen as a scaffold (ADSCs
      and SVF groups). The conduits were grafted on to the nerve defects. As the
      control, the defect was bridged with polyglycolic acid-collagen nerve conduits
      without cells. At 13 weeks, after transplantation, the regenerated nerves were
      evaluated physiologically and histologically. The compound muscle action
      potential of the SVF group was significantly higher in amplitude than that of the
      control group. Electron microscopy showed that the axon diameter of the SVF group
      was the largest, followed by the ADSC group and control group with significant
      differences among them. The SVF group had the largest fiber diameter, followed by
      the ADSC group and control group with significant differences among them. The
      ADSC group had the highest myelin thickness, followed by the SVF group and
      control group with significant differences among them. Identical excellent
      promoting effects on nerve regeneration were observed in both the ADSC and SVF
      groups. Using SVF in conduits was more practical than using ADSCs because only
      the enzymatic process was required to prepare SVF, indicating that SVF could be
      more suitable to induce nerve regeneration.

PMID- 30118578
TI  - A Core-Shell-Structured Silver Nanowire/Nitrogen-Doped Carbon Catalyst for
      Enhanced and Multifunctional Electrofixation of CO2.
AB  - Numerous catalysts have been successfully introduced for CO2 fixation in aqueous
      or organic systems. However, a single catalyst showing activity in both solvent
      types is still rare, to the best of our knowledge. We developed a core-shell
      structured AgNW/NC700 composite using a Ag nanowire (NW) core encapsulated by a N
      doped carbon (NC) shell at 700  degrees C. Through control experiments and
      density functional theory calculations, it was confirmed that Ag nanowires acted
      as the active sites for CO2 fixation and the uniformly coating of N-doped carbon
      created a CO2 -rich environment around the Ag nanowires, which could
      significantly improve the catalytic activity of Ag nanowires for electrochemical
      CO2 fixation. Under mild conditions, up to 96 % faradaic efficiency of CO, 95 %
      yield of Ibuprofen and 92 % yield of propylene carbonate could be obtained in the
      electrochemical CO2 direct reduction, carboxylation and cycloaddition,
      respectively, using the same AgNWs/NC700 catalyst. These results might provide an
      alternative strategy for efficient electrochemical fixation of CO2 .

PMID- 30118579
TI  - Evaluation of an immunochromatographic strip test for alpha-thalassaemia
      screening.
AB  - INTRODUCTION: Hb H inclusion test (HbH-i) commonly used for alpha-thalassaemia
      screening is not standardised and is labour-intensive. This study evaluated a
      strip test based on immunochromatographic detection of Hb Bart's (ICT) for use as
      a routine screening test for alpha-thalassaemia screening in the clinical
      laboratory setting. METHODS: The performance characteristics of the ICT was
      determined by comparing the results of ICT and HbH-i on 67 patients, and the
      alpha-globin genotype on 47 of these patients who also had the molecular
      analysis. Specimen stability was tested on 16 specimens with the ICT repeated
      after 7 days of storage. The age of babies from which the ICT result becomes
      valid was determined on 49 samples with patient age ranged from 4 weeks to 12
      months. RESULTS: The ICT had higher overall sensitivity of 76% compared to 24%
      for HbH-i in detecting carriers of alpha-thalassaemia mutations, and this is seen
      in all alpha-thalassaemia genotypes. The test could be carried out on specimens
      stored at 4 degrees C for 7 days and gave valid results with no false positive
      from the age of 6 months onwards. It required no special technical expertise or
      equipment and gave the result in less than 5 minutes. CONCLUSION: The ICT is
      simple to perform, with higher sensitivity than HbH-i, and gives the result in a
      short time and at a lower cost. This can be used by clinical laboratories to
      replace HbH-i for alpha-thalassaemia detection.

PMID- 30118580
TI  - Bisphosphonate Functionalized Gadolinium Oxide Nanoparticles Allow Long-Term
      MRI/CT Multimodal Imaging of Calcium Phosphate Bone Cement.
AB  - Direct in vivo monitoring of bioconstructs using noninvasive imaging modalities
      such as magnetic resonance imaging (MRI) or computed tomography (CT) is not
      possible for many materials. Calcium phosphate-based composites (CPCs) that are
      applicable to bone regeneration are an example where the materials have poor MRI
      and CT contrast; hence, they are challenging to detect in vivo. In this study, a
      CPC construct is designed with gadolinium-oxide nanoparticles incorporated to act
      as an MRI/CT multimodal contrast agent. The gadolinium(III) oxide nanoparticles
      are synthesized via the polyol method and surface functionalized with a
      bisphosphonate (BP) derivative to give a construct (gadolinium-based contrast
      agents (GBCAs)-BP) with strong affinity toward calcium phosphate. The CPC-GBCAs
      BP functional material is longitudinally monitored after in vivo implantation in
      a condyle defect rat model. The synthetic method developed produces nanoparticles
      that are stable in aqueous solution (hydrodynamic diameter 70 nm) with
      significant T1 and T2 relaxivity demonstrated in both clinical 3 T and
      preclinical 11.7 T MRI systems. The combination of GBCAs-BP nanoparticles with
      CPC gives an injectable material with handling properties that are suitable for
      clinical applications. The BP functionalization prolongs the residence of the
      contrast agent within the CPC to allow long-term follow-up imaging studies. The
      useful contrast agent properties combined with biological compatibility indicate
      further investigation of the novel bone substitute hybrid material toward
      clinical application.

PMID- 30118581
TI  - Harnessing the MinION: An example of how to establish long-read sequencing in a
      laboratory using challenging plant tissue from Eucalyptus pauciflora.
AB  - Long-read sequencing technologies are transforming our ability to assemble highly
      complex genomes. Realizing their full potential is critically reliant on
      extracting high-quality, high-molecular-weight (HMW) DNA from the organisms of
      interest. This is especially the case for the portable MinION sequencer which
      enables all laboratories to undertake their own genome sequencing projects, due
      to its low entry cost and minimal spatial footprint. One challenge of the MinION
      is that each group has to independently establish effective protocols for using
      the instrument, which can be time-consuming and costly. Here, we present a
      workflow and protocols that enabled us to establish MinION sequencing in our own
      laboratories, based on optimizing DNA extraction from a challenging plant tissue
      as a case study. Following the workflow illustrated, we were able to reliably and
      repeatedly obtain >6.5 Gb of long-read sequencing data with a mean read length of
      13 kb and an N50 of 26 kb. Our protocols are open source and can be performed in
      any laboratory without special equipment. We also illustrate some more elaborate
      workflows which can increase mean and average read lengths if this is desired. We
      envision that our workflow for establishing MinION sequencing, including the
      illustration of potential pitfalls and suggestions of how to adapt it to other
      tissue types, will be useful to others who plan to establish long-read sequencing
      in their own laboratories.

PMID- 30118582
TI  - Randomized Clinical Trial of Intravenous Acetaminophen as an Analgesic Adjunct
      for Older Adults With Acute Severe Pain.
AB  - OBJECTIVES: Older adults are at risk for undertreatment of pain. We examined
      intravenous (IV) acetaminophen as an analgesic adjunct to IV opioids in the care
      of older emergency department (ED) patients with acute severe pain. METHODS: This
      was a randomized clinical trial conducted in two EDs in the Bronx, New York.
      Eligible adults aged 65 years and older with acute severe pain were randomized to
      0.5 mg of IV hydromorphone and 1 g of IV acetaminophen or 0.5 mg of IV
      hydromorphone and 100 mL of normal saline placebo. The primary outcome was the
      between group difference in improvement of numerical rating scale (NRS) pain
      scores at 60 minutes. Secondary outcomes were the between-group differences in
      the proportion of patients who chose to forgo additional pain medications at 60
      minutes; the proportion who developed side effects; the proportion who required
      rescue analgesia; and between-group differences in NRS pain scores at 5, 15, 30,
      and 45 minutes. RESULTS: Eighty-one patients were allocated to each arm. Eighty
      patients in the IV acetaminophen arm and 79 patients in the placebo arm had
      sufficient data for analysis. At 60 minutes, patients in the hydromorphone + IV
      acetaminophen group improved by 5.7 NRS units while those in the hydromorphone +
      placebo group improved by 5.2 NRS units, for a difference of 0.6 NRS units (95%
      confidence interval [CI] = -0.4 to 1.5). A total of 28.7% of patients in the
      hydromorphone + IV acetaminophen group wanted more analgesia at 60 minutes versus
      29.1% in the hydromorphone + placebo group, for a difference of -0.4% (95% CI = 
      14.3% to 13.5%). These differences were neither clinically nor statistically
      significant. Safety profiles were similar in both groups. CONCLUSION: In this
      randomized clinical trial, the addition of IV acetaminophen to IV hydromorphone
      as an adjunctive analgesic for acute, severe, pain in older adults provided
      neither clinically nor statistically superior pain relief when compared to
      hydromorphone alone within the first hour of treatment.

PMID- 30118583
TI  - Slc26a3 deficiency is associated with epididymis dysplasia and impaired sperm
      fertilization potential in the mouse.
AB  - Members of the solute carrier 26 (SLC26) family have emerged as important players
      in mediating anions fluxes across the plasma membrane of epithelial cells, in
      cooperation with the cystic fibrosis transmembrane conductance regulator (CFTR)
      chloride channel. Among them, SLC26A3 acts as a chloride/bicarbonate exchanger,
      highly expressed in the gastrointestinal, pancreatic and renal tissues. In
      humans, mutations in the SLC26A3 gene were shown to induce congenital chloride
      losing diarrhea (CLD), a rare autosomal recessive disorder characterized by life
      long secretory diarrhea. In view of some reports indicating subfertility in some
      male CLD patients together with SLC26-A3 and -A6 expression in the male genital
      tract and sperm cells, we analyzed the male reproductive parameters and functions
      of SLC26A3 deficient mice, which were previously reported to display CLD gastro
      intestinal features. We show that in contrast to Slc26a6, deletion of Slc26a3 is
      associated with severe lesions and abnormal cytoarchitecture of the epididymis,
      together with sperm quantitative, morphological and functional defects, which
      altogether compromised male fertility. Overall, our work provides new insight
      into the pathophysiological mechanisms that may alter the reproductive functions
      and lead to male subfertility in CLD patients, with a phenotype reminiscent of
      that induced by CFTR deficiency in the male genital tract.

PMID- 30118584
TI  - Generation of High-Order All-Aqueous Emulsion Drops by Osmosis-Driven Phase
      Separation.
AB  - Droplets containing ternary mixtures can spontaneously phase-separate into high
      order structures upon a change in composition, which provides an alternative
      strategy to form multiphase droplets. However, existing strategies always involve
      nonaqueous solvents that limit the potential applications of the resulting
      multiple droplets, such as encapsulation of biomolecules. Here, a robust approach
      to achieve high-order emulsion drops with an all-aqueous nature from two aqueous
      phases by osmosis-induced phase separation on a microfluidic platform is
      presented. This technique is enabled by the existence of an interface of the two
      aqueous phases and phase separation caused by an osmolality difference between
      the two phases. The complexity of emulsion drops induced by phase separation
      could be controlled by varying the initial concentration of solutes and is
      systematically illustrated in a state diagram. In particular, this technique is
      utilized to successfully achieve high-order all-aqueous droplets in a different
      aqueous two-phase system. The proposed method is simple since it only requires
      two initial aqueous solutions for generating multilayered, organic-solvent-free
      all-aqueous emulsion drops, and thus these multiphase emulsion drops can be
      further tailored to serve as highly biocompatible material templates.

PMID- 30118585
TI  - Direct-Write Formation and Dissolution of Silver Nanofilaments in Ionic Liquid
      Polymer Electrolyte Composites.
AB  - Materials with reconfigurable optical properties are candidates for applications
      such as optical cloaking and wearable sensors. One approach to fabricate these
      materials is to use external fields to form and dissolve nanoscale conductive
      channels in well-defined locations within a polymer. In this study, conductive
      atomic force microscopy is used to electrochemically form and dissolve nanoscale
      conductive filaments at spatially distinct points in a polyethylene glycol
      diacrylate (PEGDA)-based electrolyte blended with varying amounts of ionic liquid
      (IL) and silver salt. The fastest filament formation and dissolution times are
      detected in a PEGDA/IL composite that has the largest modulus (several GPa) and
      the highest polymer crystal fraction. This is unexpected because filament
      formation and dissolution events are controlled by ion transport, which is
      typically faster within amorphous regions where polymer mobility is high.
      Filament kinetics in primarily amorphous and crystalline regions are measured,
      and two different mechanisms are observed. The formation time distributions show
      a power-law dependence in the crystalline regions, attributable to hopping-based
      ion transport, while amorphous regions show a normal distribution. The results
      indicate that the timescale of filament formation/dissolution is determined by
      local structure, and suggest that structure could be used to tune the optical
      properties of the film.

PMID- 30118586
TI  - Pre-eclampsia: a possible role for Fas/FasL gene polymorphism in its aetiology.

PMID- 30118588
TI  - Furamidine Rescues Myotonic Dystrophy Type I Associated Mis-Splicing through
      Multiple Mechanisms.
AB  - Myotonic dystrophy type 1 (DM1) is an autosomal dominant, CTG*CAG microsatellite
      expansion disease. Expanded CUG repeat RNA sequester the muscleblind-like (MBNL)
      family of RNA-binding proteins, thereby disrupting their normal cellular function
      which leads to global mis-regulation of RNA processing. Previously, the small
      molecule furamidine was shown to reduce CUG foci and rescue mis-splicing in a DM1
      HeLa cell model and to rescue mis-splicing in the HSALR DM1 mouse model, but
      furamidine's mechanism of action was not explored. Here we use a combination of
      biochemical, cell toxicity, and genomic studies in DM1 patient-derived myotubes
      and the HSALR DM1 mouse model to investigate furamidine's mechanism of action.
      Mis-splicing rescue was observed in DM1 myotubes and the HSALR DM1 mouse with
      furamidine treatment. Interestingly, while furamidine was found to bind CTG*CAG
      repeat DNA with nanomolar affinity, a reduction in expanded CUG repeat transcript
      levels was observed in the HSALR DM1 mouse but not DM1 patient-derived myotubes.
      Further investigation in these cells revealed that furamidine treatment at
      nanomolar concentrations led to up-regulation of MBNL1 and MBNL2 protein levels
      and a reduction of ribonuclear foci. Additionally, furamidine was shown to bind
      CUG RNA with nanomolar affinity and disrupted the MBNL1 -CUG RNA complex in vitro
      at micromolar concentrations. Furamidine's likely promiscuous interactions in
      vitro and in vivo appear to affect multiple pathways in the DM1 mechanism to
      rescue mis-splicing, yet surprisingly furamidine was shown globally to rescue
      many mis-splicing events with only modest off-target effects on gene expression
      in the HSALR DM1 mouse model. Importantly, over 20% of the differentially
      expressed genes were shown to be returned, to varying degrees, to wild-type
      expression levels.

PMID- 30118587
TI  - Homo-PROTACs for the Chemical Knockdown of Cereblon.
AB  - The immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide,
      all approved for the treatment of multiple myeloma, induce targeted
      ubiquitination and degradation of Ikaros (IKZF1) and Aiolos (IKZF3) via the
      cereblon (CRBN) E3 ubiquitin ligase. IMiD-based proteolysis-targeting chimeras
      (PROTACs) can efficiently recruit CRBN to a protein of interest, leading to its
      ubiquitination and proteasomal degradation. By linking two pomalidomide
      molecules, we designed homobifunctional, so-called homo-PROTACs and investigated
      their ability to induce self-directed ubiquitination and degradation. The
      homodimerized compound 15a was characterized as a highly potent and efficient
      CRBN degrader with only minimal effects on IKZF1 and IKZF3. The cellular
      selectivity of 15a for CRBN degradation was confirmed at the proteome level by
      quantitative mass spectrometry. Inactivation by compound 15a did not affect
      proliferation of different cell lines, prevented pomalidomide-induced degradation
      of IKZF1 and IKZF3, and antagonized the effects of pomalidomide on multiple
      myeloma cells. Homobifunctional CRBN degraders will be useful tools for future
      biomedical investigations of CRBN-related signaling and may help to further
      elucidate the molecular mechanism of thalidomide analogues.

PMID- 30118589
TI  - Sequencing Grade Tandem Mass Spectrometry for Top-Down Proteomics Using Hybrid
      Electron Capture Dissociation Methods in a Benchtop Orbitrap Mass Spectrometer.
AB  - Compared to traditional collision induced dissociation methods, electron capture
      dissociation (ECD) provides more comprehensive characterization of large peptides
      and proteins as well as preserves labile post-translational modifications.
      However, ECD experiments are generally restricted to the high magnetic fields of
      FTICR-MS that enable the reaction of large polycations and electrons. Here, we
      demonstrate the use of an electromagnetostatic ECD cell to perform ECD and hybrid
      ECD methods utilizing 193 nm photons (ECuvPD) or collisional activation (EChcD)
      in a benchtop quadrupole-Orbitrap mass spectrometer. The electromagnetostatic ECD
      cell was designed to replace the transfer octapole between the quadrupole and C
      trap. This implementation enabled facile installation of the ECD cell, and ions
      could be independently subjected to ECD, UVPD, HCD, or any combination. Initial
      benchmarking and characterization of fragmentation propensities for ECD, ECuvPD,
      and EChcD were performed using ubiquitin (8.6 kDa). ECD yielded extensive
      sequence coverage for low charge states of ubiquitin as well as for the larger
      protein carbonic anhydrase II (29 kDa), indicating pseudo-activated ion
      conditions. Additionally, relatively high numbers of d- and w-ions enable
      differentiation of isobaric isoleucine and leucine residues and suggest a
      distribution of electron energies yield hot-ECD type fragmentation. We report the
      most comprehensive characterization to date for model proteins up to 29 kDa and a
      monoclonal antibody at the subunit level. ECD, ECuvPD, and EChcD yielded 93, 95,
      and 91% sequence coverage, respectively, for carbonic anhydrase II (29 kDa), and
      targeted online analyses of monoclonal antibody subunits yielded 86% overall
      antibody sequence coverage.

PMID- 30118590
TI  - High F-Content Perfluoropolyether-Based Nanoparticles for Targeted Detection of
      Breast Cancer by 19F Magnetic Resonance and Optical Imaging.
AB  - Two important challenges in the field of 19F magnetic resonance imaging (MRI) are
      the maintenance of high fluorine content without compromising imaging
      performance, and effective targeting of small particles to diseased tissue. To
      address these challenges, we have developed a series of perfluoropolyether (PFPE)
      based hyperbranched (HBPFPE) nanoparticles with attached peptide aptamer as
      targeting ligands for specific in vivo detection of breast cancer with high 19F
      MRI sensitivity. A detailed comparison of the HBPFPE nanoparticles (NPs) with the
      previously reported trifluoroethyl acrylate (TFEA)-based polymers demonstrates
      that the mobility of fluorinated segments of the HBPFPE nanoparticles is
      significantly enhanced (19F T2 > 80 ms vs 31 ms), resulting in superior MR
      imaging sensitivity. Selective targeting was confirmed by auto- and pair
      correlation analysis of fluorescence microscopy data, in vitro
      immunofluorescence, in vivo 19F MRI, ex vivo fluorescence and 19F NMR. The
      results highlight the high efficiency of aptamers for targeting and the excellent
      sensitivity of the PFPE moieties for 19F MRI. Of relevance to in vivo
      applications, the PFPE-based polymers exhibit much faster clearance from the body
      than the previously introduced perfluorocarbon emulsions ( t1/2 ~ 20 h vs up to
      months). Moreover, the aptamer-conjugated NPs show significantly higher tumor
      penetration, demonstrating the potential of these imaging agents for therapeutic
      applications. This report of the synthesis of polymeric aptamer-conjugated PFPE
      based 19F MRI CAs with high fluorine content (~10 wt %) demonstrates that these
      NPs are exciting candidates for detecting diseases with high imaging sensitivity.

PMID- 30118591
TI  - Ingested Micronizing Plastic Particle Compositions and Size Distributions within
      Stranded Post-Hatchling Sea Turtles.
AB  - From July 2015 to November 2016, 96 post-hatchling sea turtles were collected
      from 118 km of the Atlantic coastline in Florida, USA, including loggerhead,
      green, and hawksbill sea turtle species. Forty-five of the recovered turtles were
      rehabilitated and released, but the remaining 52 died and were frozen. At
      necropsy, the gastrointestinal tracts of most the turtles contained visible
      plastic, and collected particles of 27 individuals were chemically characterized
      by Raman microscopy as polyethylene, polypropylene, polyethylene terephthalate,
      and polystyrene. Mesoparticle plastic fragments 1.0-8.7 mm, microparticle
      fragments 20-1000 MUm, and nanoparticles 5-169 nm were identified in the turtles.
      Polyethylene and polypropylene were the most common plastics ingested from
      specimens representing 54.1 and 23.7% of the total observed mesoparticles and
      11.7 and 21.0% of the total observed microparticles, respectively. A plastic-to
      body mass ratio of 2.07 mg/g was determined for this group. The authors suggest
      that ingestion of micronizing plastic by post-hatchling sea turtles is likely a
      substantial risk to survival of these endangered and threatened species. This
      study also provides some of the first evidence for the formation of nanoscopic
      plastic particles that we theorize forms in the post-hatchling and juvenile
      environment and are present post-ingestion.

PMID- 30118592
TI  - Negative Photoconductance in van der Waals Heterostructure-Based Floating Gate
      Phototransistor.
AB  - van der Waals (vdW) heterostructures made of two-dimensional materials have been
      demonstrated to be versatile architectures for optoelectronic applications due to
      strong light--matter interactions. However, most light-controlled phenomena and
      applications in the vdW heterostructures rely on positive photoconductance (PPC).
      Negative photoconductance (NPC) has not yet been reported in vdW
      heterostructures. Here we report the observation of the NPC in the ReS2/h-BN/MoS2
      vdW heterostructure-based floating gate phototransistor. The fabricated devices
      exhibit excellent performance of nonvolatile memory without light illumination.
      More interestingly, we observe a gate-tunable transition between the PPC and the
      NPC under the light illumination. The observed NPC phenomenon can be attributed
      to charge transfer between the floating gate and the conduction channel.
      Furthermore, we show that control of NPC through light intensity is promising in
      realization of light-tunable multibit memory devices. Our results may enable
      potential applications in multifunctional memories and optoelectronic devices.

PMID- 30118593
TI  - Frechet ChemNet Distance: A Metric for Generative Models for Molecules in Drug
      Discovery.
AB  - The new wave of successful generative models in machine learning has increased
      the interest in deep learning driven de novo drug design. However, method
      comparison is difficult because of various flaws of the currently employed
      evaluation metrics. We propose an evaluation metric for generative models called
      Frechet ChemNet distance (FCD). The advantage of the FCD over previous metrics is
      that it can detect whether generated molecules are diverse and have similar
      chemical and biological properties as real molecules.

PMID- 30118594
TI  - Development of High-Capacity Periodate Battery with Three-Dimensional-Printed
      Casing Accommodating Replaceable Flexible Electrodes.
AB  - We present the development of a novel battery comprising iron(III) periodate
      complex cathode and zinc anode. The periodate complex [H7Fe4(IO4)3O8] was
      prepared by a precipitation reaction between Fe(NO3)3 and NaIO4 and was used in
      battery development for the first time. The periodate complex along with 14%
      carbon nanotubes and a polytetrafluoroethylene coating formed a stable flexible
      electrode, and the battery showed specific capacity as high as 300 mA h g-1.
      Compared to single-electron processes in conventional cathode reactions, the
      possibility to significantly enhancing the cathode specific capacity via a
      multielectron process associated with valence change from I(VII) to I2 is
      demonstrated. A novel three-dimensional printed reserve battery design comprising
      replaceable electrodes and acetic acid electrolyte is also presented.

PMID- 30118595
TI  - Highly Robust, Transparent, and Breathable Epidermal Electrode.
AB  - Recently emerged electronic skins with applications in on-body sensing and human
      machine interfaces call for the development of high-performance skin-like
      electrodes. In this work, we report a highly robust, transparent, and breathable
      epidermal electrode composed of a scaffold-reinforced conductive nanonetwork
      (SRCN). Solution-dispersed Ag nanowires, through facile vacuum filtration, are
      embedded into a scaffold made of polyamide nanofibers. Optical transmittance of
      84.9% at 550 nm wavelength is achieved at a significantly low sheet resistance of
      8.2 Omega sq-1. The resistance of the SRCN only slightly increases by less than
      0.1% after being bent for 3000 cycles at the maximum curvature of 300 m-1 and by
      less than 1.5% after being dipped in saline solution for 2500 cycles. The
      excellent robustness is attributed to the reinforcement from the nanofiber-based
      scaffold as a backbone that maintains the connections among the Ag nanowires by
      undertaking most of the loaded stress. The SRCN not only forms tight and
      conformal bonding with the target surface but also allows the evaporation of
      perspiration, making it suitable as an epidermal electrode for long-time use.
      Furthermore, fine and clean-cut circuit patterns with a line width on the
      micrometer scale can be readily prepared, paving the way for fabricating
      sophisticated functional electronic skins.

PMID- 30118598
TI  - Distinguishing Emission-Associated Ambient Air PM2.5 Concentrations and
      Meteorological Factor-Induced Fluctuations.
AB  - Although PM2.5 (particulate matter with aerodynamic diameters less than 2.5 MUm)
      in the air originates from emissions, its concentrations are often affected by
      confounding meteorological effects. Therefore, direct comparisons of PM2.5
      concentrations made across two periods, which are commonly used by environmental
      protection administrations to measure the effectiveness of mitigation efforts,
      can be misleading. Here, we developed a two-step method to distinguish the
      significance of emissions and meteorological factors and assess the effectiveness
      of emission mitigation efforts. We modeled ambient PM2.5 concentrations from 1980
      to 2014 based on three conditional scenarios: realistic conditions, fixed
      emissions, and fixed meteorology. The differences found between the model outputs
      were analyzed to quantify the relative contributions of emissions and
      meteorological factors. Emission-related gridded PM2.5 concentrations excluding
      the meteorological effects were predicted using multivariate regression models,
      whereas meteorological confounding effects on PM2.5 fluctuations were
      characterized by probabilistic functions. When the regression models and
      probabilistic functions were combined, fluctuations in the PM2.5 concentrations
      induced by emissions and meteorological factors were quantified for all model
      grid cells and regions. The method was then applied to assess the historical and
      future trends of PM2.5 concentrations and potential fluctuations on global,
      national, and city scales. The proposed method may thus be used to assess the
      effectiveness of mitigation actions.

PMID- 30118597
TI  - Spatially Resolved Proteome Profiling of <200 Cells from Tomato Fruit Pericarp by
      Integrating Laser-Capture Microdissection with Nanodroplet Sample Preparation.
AB  - Due to sensitivity limitations, global proteome measurements generally require
      large amounts of biological starting material, which masks heterogeneity within
      the samples and differential protein expression among constituent cell types.
      Methods for spatially resolved proteomics are being developed to resolve protein
      expression for distinct cell types among highly heterogeneous tissues, but have
      primarily been applied to mammalian systems. Here we evaluate the performance of
      cell-type-specific proteome analysis of tomato fruit pericarp tissues by a
      platform integrating laser-capture microdissection (LCM) and a recently developed
      automated sample preparation system (nanoPOTS, nanodroplet processing in one pot
      for trace samples). Tomato fruits were cryosectioned prior to LCM and tissues
      were dissected and captured directly into nanoPOTS chips for processing.
      Following processing, samples were analyzed by nanoLC-MS/MS. Approximately 1900
      unique peptides and 422 proteins were identified on average from ~0.04 mm2
      tissues comprising ~8-15 parenchyma cells. Spatially resolved proteome analyses
      were performed using cells of outer epidermis, collenchyma, and parenchyma. Using
      <=200 cells, a total of 1,870 protein groups were identified and the various
      tissues were easily resolved. The results provide spatial and tissue-specific
      insights into key enzymes and pathways involved in carbohydrate transport and
      source-sink relationships in tomato fruit. Of note, at the time of fruit ripening
      studied here, we identified differentially abundant proteins throughout the
      pericarp related to chlorophyll biogenesis, photosynthesis, and especially
      transport.

PMID- 30118599
TI  - Conventional Ultrafiltration As Effective Strategy for Dye/Salt Fractionation in
      Textile Wastewater Treatment.
AB  - Use of tight ultrafiltration (UF) membranes has created a new pathway in
      fractionation of dye/salt mixtures from textile wastewater for sustainable
      resource recovery. Unexpectedly, a consistently high rejection for the dyes with
      smaller sizes related to the pore sizes of tight UF membranes is yielded. The
      potential mechanism involved in this puzzle remains unclear. In this study, seven
      tailored UF membranes with molecular weight cut-offs (MWCOs) from 6050 to 17530
      Da were applied to separate dye/salt mixtures. These UF membranes allowed a
      complete transfer for NaCl and Na2SO4, due to large pore sizes. Additionally,
      these UF membranes had acceptably high rejections for direct and reactive dyes,
      due to the aggregation of dyes as clusters for enhanced sizes and low
      diffusivity. Specifically, the membrane with an MWCO of 7310 Da showed a complete
      rejection for reactive blue 2 and direct dyes. An integrated UF-diafiltration
      process was subsequently designed for fractionation of reactive blue 2/Na2SO4
      mixture, achieving 99.84% desalination efficiency and 97.47% dye recovery.
      Furthermore, reactive blue 2 can be concentrated from 2.01 to 31.80 g.L-1. These
      results indicate that UF membranes even with porous structures are promising for
      effective fractionation of dyes and salts in sustainable textile wastewater
      treatment.

PMID- 30118596
TI  - Improved Sensitivity and Separations for Phosphopeptides using Online Liquid
      Chromotography Coupled with Structures for Lossless Ion Manipulations Ion
      Mobility-Mass Spectrometry.
AB  - Phosphoproteomics greatly augments proteomics and holds tremendous potential for
      insights into the modulation of biological systems for various disease states.
      However, numerous challenges hinder conventional methods in terms of measurement
      sensitivity, throughput, quantification, and capabilities for confident
      phosphopeptide and phosphosite identification. In this work, we report the first
      example of integrating structures for lossless ion manipulations ion mobility
      mass spectrometry (SLIM IM-MS) with online reversed-phase liquid chromatography
      (LC) to evaluate its potential for addressing the aforementioned challenges. A
      mixture of 51 heavy-labeled phosphopeptides was analyzed with a SLIM IM module
      having integrated ion accumulation and long-path separation regions. The SLIM IM
      MS provided limits of detection as low as 50-100 pM (50-100 amol/MUL) for several
      phosphopeptides, with the potential for significant further improvements. In
      addition, conventionally problematic phosphopeptide isomers could be resolved
      following an 18 m SLIM IM separation. The 2-D LC-IM peak capacity was estimated
      as ~9000 for a 90 min LC separation coupled to an 18 m SLIM IM separation,
      considerably higher than LC alone and providing a basis for both improved
      identification and quantification, with additional gains projected with the
      future use of longer path SLIM IM separations. Thus, LC-SLIM IM-MS offers great
      potential for improving the sensitivity, separation, and throughput of
      phosphoproteomics analyses.

PMID- 30118600
TI  - MetaboGroup S: A Group Entropy-Based Web Platform for Evaluating Normalization
      Methods in Blood Metabolomics Data from Maintenance Hemodialysis Patients.
AB  - Because of inevitable and complicated signal variations in LC-MSn-based
      nontargeted metabolomics, normalization of metabolites data is a highly
      recommended procedure to assist in improving accuracies in metabolic profiling
      and discovery of potential biomarkers. Despite various normalization methods
      having been developed and applied for processing these data sets, it is still
      difficult to assess their performance. Moreover, such methods are elusive and
      difficult to choose for users, especially those without bioinformatics training.
      In this study, we present a powerful and user-friendly web platform, named
      MetaboGroup S, for comparison and evaluation of seven popular normalization
      methods and provide an optimal one automatically for end users based on the group
      entropies of every sample data point. For examination and application of this
      tool, we analyzed a complex clinical human data set from maintenance hemodialysis
      patients with erythrin resistance. Metabolite peaks (11 027) were extracted from
      the experimental data and then imported into this platform; the entire analysis
      process was completed sequentially within 5 min. To further test the performance
      and universality of MetaboGroup S, we analyzed two more published data sets
      including a nuclear magnetic resonance (NMR) data set on this platform. The
      results indicated that the method with a lower intragroup entropy and higher
      intergroup entropy would be preferable. In addition, MetaboGroup S can be quite
      conveniently operated by users and does not require any profound computational
      expertise or background for scientists in many fields. MetaboGroup S is freely
      available at https://omicstools.shinyapps.io/MetaboGroupSapp/ .

PMID- 30118601
TI  - The Quest for Accurate Liquid Water Properties from First Principles.
AB  - Developing accurate ab initio molecular dynamics (AIMD) models that capture both
      electronic reorganization and nuclear quantum effects associated with hydrogen
      bonding is key to quantitative understanding of bulk water and its anomalies as
      well as its role as a universal solvent. For condensed phase simulations, AIMD
      has typically relied on the generalized gradient approximation (GGA) of density
      functional theory (DFT) as the underlying model chemistry for the potential
      energy surface, with nuclear quantum effects (NQEs) sometimes modeled by
      performing classical molecular dynamics simulations at elevated temperatures.
      Here we show that the properties of liquid water obtained from the meta-GGA B97M
      rV functional, when evaluated using accelerated path integral molecular dynamics
      simulations, display accuracy comparable to a computationally expensive
      dispersion-corrected hybrid functional, revPBE0-D3. We show that the meta-GGA DFT
      functional reproduces bulk water properties including radial distribution
      functions, self-diffusion coefficients, and infrared spectra with comparable
      accuracy of a much more expensive hybrid functional. This work demonstrates that
      the underlying quality of a good DFT functional requires evaluation with quantum
      nuclei and that high-temperature simulations are a poor proxy for properly
      treating NQEs.

PMID- 30118602
TI  - Detecting Proline and Non-Proline Cis Isomers in Protein Structures from
      Sequences Using Deep Residual Ensemble Learning.
AB  - It has been long established that cis conformations of amino acid residues play
      many biologically important roles despite their rare occurrence in protein
      structure. Because of this rarity, few methods have been developed for predicting
      cis isomers from protein sequences, most of which are based on outdated datasets
      and lack the means for independent testing. In this work, using a database of
      >10000 high-resolution protein structures, we update the statistics of cis
      isomers and develop a sequence-based prediction technique using an ensemble of
      residual convolutional and long short-term memory bidirectional recurrent neural
      networks that allow learning from the whole protein sequence. We show that
      ensembling eight neural network models yields maximum Matthews correlation
      coefficient values of approximately 0.35 for cis-Pro isomers and 0.1 for cis
      nonPro residues. The method should be useful for prioritizing functionally
      important residues in cis isomers for experimental validations and improving the
      sampling of rare protein conformations for ab initio protein structure
      prediction.

PMID- 30118604
TI  - Practical Considerations in High-Precision Compound-Specific Radiocarbon
      Analyses: Eliminating the Effects of Solvent and Sample Cross-Contamination on
      Accuracy and Precision.
AB  - Preparative capillary gas chromatography (pcGC) is widely used for the isolation
      of single compounds for radiocarbon determinations. While being effective at
      isolating compounds, there are still genuine concerns relating to contamination
      associated with the isolation procedure, such as incomplete removal of solvent
      used to recover isolated compounds from the traps and cross-contamination, which
      can lead to erroneous 14C determinations. Herein we describe new approaches to
      identifying and removing these two sources of contamination. First, we replaced
      the common "U" trap design, which requires recovery of compounds using organic
      solvent, with a novel solventless trapping system (STS), consisting of a simple
      glass tube containing a glass wool plug, allowing condensation of a target
      compound in the wool and its solventless recovery by pushing the glass wool
      directly into a foil capsule for graphitization. With the STS trap, an average of
      95.7% of the target compound was recovered, and contamination from column bleed
      was reduced. In addition, comparison of 14C determinations of fatty acid methyl
      ester (FAME) standards determined offline to those isolated by pcGC in STS traps
      showed excellent reproducibility and accuracy compared to those isolated using
      the commercial "U" traps. Second, "coldspots" were identified in the instrument,
      i.e., the termini of capillaries in the preparative unit, which can be cleaned of
      compounds condensed from earlier runs using a heat gun. Our new procedure,
      incorporating these two modifications, was tested on archeological fat hoards,
      producing 14C dates on isolated C16:0 and C18:0 fatty acids statistically
      consistent with the bulk dates of the archeological material.

PMID- 30118605
TI  - Assessing the Prevalence and Predictors of Bullying Among Emergency Medical
      Service Providers.
AB  - BACKGROUND: Bullying as a stressor in the workplace has been evaluated in
      numerous settings. It has never been evaluated in the emergency medical service
      (EMS) environment where bullying can occur from many different sources. The
      Negative Acts Questionnaire-Revised (NAQ-R) is a 22-question validated tool for
      evaluating bullying. Our hypothesis was that we could identify a shortened
      version of the NAQ-R that identifies bullying as accurately as the full screening
      tool. METHODS: This was a cross sectional study of EMS providers in our local EMS
      transport agency. The local EMS agency transports approximately 50,000 patients
      per year and is a paramedic level response system. Results on the NAQ-R were on a
      5-point Likert scale for each of 22 different categories of bullying that were
      summed by adding each questions 1-5 response for the 22 questions. Respondents
      were also categorized as victims or non-victims of bullying based on being
      positive for any of the 22 types of bullying at least once a week. We performed a
      binomial decision tree analysis and a cross-validation. RESULTS: Data were
      collected from 153 providers. Mean age was 33 +/- 10 years and 50% were male.
      Total years in EMS were 8 +/- 8 years. NAQ-R summed results in our group ranged
      between 22 and 88, with an average of 40 +/- 15. A NAQ-R score of 33 or less was
      91% accurate in identifying non-victims and a score of 45 or more was 94%
      accurate in identifying victims. The majority at 51% (77/152) of respondents were
      victims of one or more types of bullying. A combination of five questions was 94%
      accurate in identifying a victim of bullying among EMS providers. Cross
      validation resulted in a misclassification risk estimate of 0.12 +/- .03.
      CONCLUSION: NAQ-R bullying scores in EMS are similar or higher than numbers in
      other fields. Five questions on the NAQ-R were 94% accurate in identifying
      victims of bullying in EMS providers. Key words: EMS; bullying; EM;
      administration.

PMID- 30118606
TI  - Dynamics of the bacterial community in a channel catfish nursery pond with a cage
      pond integration system.
AB  - The changes in the bacterial community composition in a channel catfish nursery
      pond with a cage-pond integration system were investigated by sequencing of the
      16S rRNA gene through Illumina MiSeq sequencing platforms. A total of 1 362 877
      sequences and 1440 operational taxonomic units were obtained. Further analysis
      showed that the dominant phyla in the cage and pond groups were similar,
      including Actinobacteria, Cyanobacteria, Proteobacteria, and Bacteroidetes,
      although a significant difference was detected between them by ANOSIM (P < 0.05).
      Temporal changes and site variation were significantly related to the variation
      of the bacterial community. A comprehensive analysis of the diversity and
      evenness of the bacterial 16S rRNA gene, redundancy analysis (RDA), and partial
      Mantel test showed that the bacterial community composition in a cage-pond
      integration system was shaped more by temporal variation than by site variation.
      RDA also indicated that water temperature, total dissolved solids, and Secchi
      depth had the largest impact on bacterial populations.

PMID- 30118603
TI  - Gold Nanorod Photothermal Therapy Alters Cell Junctions and Actin Network in
      Inhibiting Cancer Cell Collective Migration.
AB  - Most cancer-related deaths come from metastasis. It was recently discovered that
      nanoparticles could inhibit cancer cell migration. Whereas most researchers focus
      on single-cell migration, the effect of nanoparticle treatment on collective cell
      migration has not been explored. Collective migration occurs commonly in many
      types of cancer metastasis, where a group of cancer cells move together, which
      requires the contractility of the cytoskeleton filaments and the connection of
      neighboring cells by the cell junction proteins. Here, we demonstrate that gold
      nanorods (AuNRs) and the introduction of near-infrared light could inhibit the
      cancer cell collective migration by altering the actin filaments and cell
      junctions with significantly triggered phosphorylation changes of essential
      proteins, using mass spectrometry-based phosphoproteomics. Further observation
      using super-resolution stochastic optical reconstruction microscopy (STORM)
      showed the actin cytoskeleton filament bundles were disturbed, which is difficult
      to differentiate under a normal fluorescence microscope. The decreased expression
      level of N-cadherin junctions and morphological changes of tight junction protein
      zonula occludens 2 were also observed. All of these results indicate possible
      functions of the AuNR treatments in regulating and remodeling the actin filaments
      and cell junction proteins, which contribute to decreasing cancer cell collective
      migration.

PMID- 30118607
TI  - A sibling study of isolated optic neuropathy associated with novel variants in
      the ACO2 gene.
AB  - Inherited optic neuropathy is a rare cause of debilitating vision loss. It may
      occur in constellation with other syndromic features of neurological impairment,
      or present as an isolated finding. We describe a sibling pair, without a family
      history of vision loss, who developed visual impairment in early childhood
      consistent with optic neuropathy. Genetic testing identified novel compound
      heterozygous variants in the aconitase 2 (ACO2) gene. To date, seven families
      hosting ACO2 variants have been described in the literature. We describe the
      second family with ACO2 variants to have an isolated optic neuropathy
      highlighting the importance of including this gene in genomic panels assessing
      inherited optic neuropathies.

PMID- 30118608
TI  - Impact of transporters and enzymes from blood-cerebrospinal fluid barrier and
      brain parenchyma on CNS drug uptake.
AB  - INTRODUCTION: In parallel with the blood-brain barrier (BBB), transporters and
      enzymes on the blood-cerebrospinal fluid barrier (BCSFB) serve as the first
      barrier for drug brain uptake. In addition, their expressions on brain parenchyma
      are considered as the secondary barrier for central nervous system (CNS) drug
      delivery. Currently, a lack of information on transporters and enzymes expressed
      on both BCSFB and brain parenchyma is the major cause of failure in CNS drug
      development. Areas covered: Transporters and enzymes expressed on BCSFB and brain
      parenchyma and their impact on drug brain uptake were highlighted and compared
      with that on BBB. Expert opinion: Based on the nature of transporters expressed
      on BCSFB and the brain parenchyma, the design of CNS therapeutics with chemical
      structures similar to the substrates of nutrients and hormones transporters could
      facilitate their CSF and brain parenchyma uptake . Moreover, drugs in systemic
      circulation could undergo further metabolism at BCSFB and brain parenchyma
      leading to failure in CNS drug delivery. Impact of the altered expressions and
      functions of transporters and enzymes on BCSFB and brain parenchyma in different
      species or disease conditions on CNS drug brain uptake shall be further evaluated
      using relevant in vitro cell models and pharmacokinetics modeling.

PMID- 30118609
TI  - Evaluating Self-Refraction and Ready-Made Spectacles for Treatment of Uncorrected
      Refractive Error.
AB  - PURPOSE: Uncorrected refractive error is the leading cause of visual impairment
      worldwide and has significant quality of life and economic implications.
      Treatment with subjective refraction and custom-made spectacles requires
      expensive equipment and highly trained personnel. We examine several
      alternatives. METHODS: Patients were taught to self-refract using two devices:
      AdSpecs and the I-test Vision Screener. Ready-made spectacles were fit to the
      self-refraction and visual acuity (VA) was measured. Donated-spectacles were fit
      to subjective refraction and VA was measured. Self-refraction and donated
      spectacles spherical equivalent (SE) and VA were compared to subjective
      refraction SE and VA. RESULTS: About 57 patients (102 eyes) were enrolled in the
      study. Patients accurately determined refractive power with self-refraction by
      both AdSpecs and the I-test (compared to subjective refraction SE, r2 = 0.97 and
      r2 = 0.94, respectively). SE of donated spectacles fit well with self-refraction
      SE (r2 = 0.91). There was no significant difference between best-corrected VA by
      subjective refraction and VA treated by ready-made spectacles fit to self
      refraction by either device (analysis of variance (ANOVA), p non-significant).
      Patients fit with donated spectacles had significantly worse VA than best
      corrected VA by subjective refraction (ANOVA, p < 0.01), although 80% improved to
      >20/40. CONCLUSION: Patients accurately self-refract using both devices and ready
      made spectacles fit to self-refraction have excellent visual outcomes. Donated
      spectacles have worse visual outcomes but might be useful in a subset of
      patients. Ready-made spectacles fit to self-refraction may provide a treatment
      alternative to uncorrected refractive error.

PMID- 30118610
TI  - The safety of bortezomib for the treatment of multiple myeloma.
AB  - INTRODUCTION: There is now 16 years' worth of established results of various
      trials demonstrating the bortezomib efficiency in the treatment of multiple
      myeloma. Over this time, the introduction of bortezomib has been a major break
      through in the treatment of multiple myeloma. Bortezomib can be administered in
      the outpatient setting with manageable toxicities. Areas covered: A literature
      search was carried out using PubMed and Google Scholar. This review gives an
      overview of the critical role of the bortezomib in multiple myeloma and provides
      a comprehensive summary of key clinical benefit and safety data with the
      bortezomib. Initial toxicity profile has improved dramatically with introduction
      of subcutaneous administration and also, implementation of guidelines for early
      recognition and treatment. Triplet and quadruplets of bortezomib with agents
      possessing similar toxicities constitute a challenge. Expert opinion: Bortezomib
      is an important part of current anti-myeloma therapy with a good clinical
      efficacy and manageable side effects. Although gastrointestinal disturbances and
      fatigue are the most common adverse effects, peripheral neuropathy and
      thrombocytopenia are the key dose-limiting toxicities of bortezomib-based
      combination regimens. Since these combinations are more effective, with faster
      disappearance of disease related symptoms and anti-inflammatory effects of
      bortezomib toxicities were not found to be augmented.

PMID- 30118611
TI  - Osseous cavernous hemangioma of the superior orbital rim.
AB  - A 53-year-old male presented with a bony lesion over the superior orbital rim
      increasing in size over several months. CT imaging showed a circumscribed,
      osseous lesion involving the outer table of the right frontal bone and superior
      orbital rim with a honeycomb appearance. Anterior orbitotomy revealed an osseous
      lesion along the superior orbital rim with purple cavernous spaces.
      Histopathological examination demonstrated cavernous vascular channels with
      variably-sized lumens and variably-thickened vascular walls interspersed among
      bony trabeculae consistent with an osseous cavernous hemangioma.

PMID- 30118612
TI  - Can We Define Termination Of Resuscitation Criteria In Out-Of-Hospital Hanging?
AB  - OBJECTIVE: Survival rate of cardiac arrest due to hanging (H-CA) victims is low.
      Hence, this leads to the question of the utility of resuscitation in these
      patients. The objective was to investigate whether there are predictive criteria
      for survival with a good neurological outcome or predictive criteria for non
      survival or survival with a poor neurological outcome enabling us to define the
      termination of resuscitation rules in these patients. METHODS: Between July 1,
      2011 and January 1, 2016, we included 1,689 out-of-hospital cardiac arrests due
      to hanging. We compared the characteristics of survivors with a good neurological
      outcome at day 30 with the others. RESULTS: The study population was mainly
      composed of males with a median age of 48 [37-60]. The overall survival was 2.1%,
      among which 48.6% had a good neurological outcome. Survivors benefited more often
      from immediate basic life support than the rest of the subjects, which was
      corroborated by the shorter no-flow durations. We did not record any difference
      in terms of advanced cardiac life support initiation frequency and technique
      between survivors with a good neurological outcome and the rest. Nevertheless,
      ACLS duration was longer in survivors with a good neurological outcome than in
      others. CONCLUSIONS: Basic life support (BLS) was the decisive criterion for
      15/17 survivors. However, a detailed analysis showed 2 survivors presenting no
      BLS before the arrival of mobile medical teams and non-shockable rhythms who
      survived at day 30 with a good neurological outcome. These results lead us to
      consider that mobile medical team intervention and ACLS attempt are not futile,
      and the benefit justifies the cost. Thus, we cannot define any rule for the
      termination of resuscitation.

PMID- 30118613
TI  - Ocular complications of severe corneal abrasions after cosmetic
      blepharopigmentation.
AB  - A 53-year-old woman with hemiparesis and poor dexterity, underwent cosmetic
      blepharopigmentation on the both upper eyelids in the dermatology clinic of a
      private hospital. She was not asked for any information on her medical history
      and no informed consent was obtained and the procedure was performed without any
      protective ocular shields. The patient experienced severe lacrimation,
      discomfort, and increased sensitivity to light during and after the procedure.
      She also noticed blurred vision after the procedure. Ophthalmologic examination
      revealed tender and oedematous eyelids and corneal abrasions in both of her eyes.
      Topical antibiotics and preservative-free lubricants were able to recover her
      from her signs and symptoms at 1-week follow-up. It is recommended that cosmetic
      blepharopigmentation should be applied cautiously with patient's informed consent
      after obtaining a thorough medical history and with protective ocular shields to
      avoid potential complications.

PMID- 30118614
TI  - Measurement of Intra-Orbital Structures in Normal Chinese Adults Based on a Three
      Dimensional Coordinate System.
AB  - PURPOSE OF THE STUDY: This study was to establish a three-dimensional (3D)
      coordinate system and to study the normal dimensions of intra-orbital structures
      in Chinese adults. MATERIALS AND METHODS: One hundred and forty-five adult
      Chinese were selected from patients who had undergone cranio-facial computed
      tomography scans with diagnosis other than orbital or ocular abnormality. An
      orbital 3D coordinate system was built on the basis of the scans. Morphological
      variables of intra-orbital structures were measured in this coordinate system.
      Bilateral symmetry, sexual dimorphism, and correlations between variables were
      investigated. RESULTS: No evident laterality was found in bilateral intra-orbital
      structures. The distance from the center of the eyeball to the prechiasmatic
      groove, the length of the optic nerve, and the thickness of rectus extraocular
      muscles were larger in males than in females. No sex-related difference was
      observed in the anteroposterior diameter of the eyeball or the exophthalmometric
      value. The exophthalmometric value was found to be related to the anteroposterior
      diameter of the eyeball, whereas the y-coordinate of the center of the eyeball
      had no correlation with the anteroposterior diameter of the eyeball. The optic
      nerve length was closely correlated to the distance from the center of the
      eyeball to the prechiasmatic groove. CONCLUSIONS: The 3D coordinate system and
      measurement method established in this study can be applied to the
      standardization of orbital morphometry. The measurements obtained from normal
      Chinese adults may provide reference values for the morphology of intra-orbital
      structures.

PMID- 30118615
TI  - A comparison of gingival depigmentation by Er:YAG laser and Kirkland knife:
      osmotic pressure and visual analog scale.
AB  - BACKGROUND: The aim of this study was to compare osmotic pressure (OP) 1 week
      after the gingival depigmentation in two diffeent methods: Er: YAG laser and
      Kirkland knife. METHODS: This study included 20 patients, 13 women, and 7 men who
      had esthetic complaints of gingival melanin hyperpigmentation. The left side of
      the maxilla and mandible were depigmented with Er:YAG laser using air and water
      spray and the right side was removed with a Kirkland knife. Gingival biopsies
      were obtained from attached gingiva of operation sides with approximate
      dimensions of 2 mm * 2 mm before and 1 week after the depigmentation. The visual
      analog scale (VAS) was used to evaluate the pain level experienced by each
      patient. RESULTS: Patients reported no pain at the gingivoplasty sides after 4
      days and at the laser sides after 3 days. There were not statistical differences
      between laser and gingivoplasty groups according to values of OP (P > 0.05).
      CONCLUSION: According to results of wound healing, OP and VAS, two depigmentation
      procedures can be used safely and effectively.

PMID- 30118616
TI  - Traumatic brain injury and stroke: does recovery differ?
AB  - BACKGROUND: Traumatic brain injury and stroke often lead to cognitive,
      neurological and psychological disorders, which can result in many difficulties.
      Despite the existence of various disorders, improving cognitive capacities may be
      possible for these two pathologies. OBJECTIVES: The purpose of this study was to
      assess cognitive recovery in patients with traumatic brain injury and stroke and
      compare recovery between both groups. PARTICIPANTS AND METHODS: Forty-nine adults
      who had suffered from mild to severe traumatic brain injury and 42 from stroke
      were assessed third with a minimum of 2 months between assessments. The French
      version of the Barrow Neurological Institute Scale was used to examine cognitive
      abilities and included six subscales on language, memory, guidance, visual
      spatial functions, affectivity and attention. RESULTS: Cognitive performances
      were similar for the two groups at both assessments, with the exception of
      language performances, which were higher for participants with traumatic brain
      injury. An improvement was observed for several cognitive abilities, but no
      significant differences were found between traumatic brain injury and stroke
      groups. CONCLUSIONS: The findings of this study reveal the possibility of
      cognitive recovery after brain damage. No recovery differences were found for
      vascular and traumatic lesions.

PMID- 30118617
TI  - Self-Assessment Feedback Form Improves Quality of Out-of-Hospital CPR.
AB  - OBJECTIVE: Various continuous quality improvement (CQI) approaches have been used
      to improve quality of cardiopulmonary resuscitation (CPR) delivered at the scene
      of out-of-hospital cardiac arrest. We evaluated a post-event, self-assessment,
      CQI feedback form to determine its impact on delivery of CPR quality metrics.
      METHODS: This before/after retrospective review evaluated data from a CQI program
      in a midsized urban emergency medical services (EMS) system using CPR quality
      metrics captured by Zoll Medical Inc. X-series defibrillator ECG files in adult
      patients (>=18 years old) with non-traumatic out-of-hospital cardiac arrest. Two
      9-month periods, one before and one after implementation of the feedback form on
      December 31, 2013 were evaluated. Metrics included the mean and percentage of
      goal achievement for chest compression depth (goal: >5 centimeters [cm];
      >90%/episode), rate (goal: 100-120 compressions/minute [min]), chest compression
      fraction (goal: >=75%), and preshock pause (goal: <10 seconds [sec]). The
      feedback form was distributed to all EMS providers involved in the resuscitation
      within 72 hours for self-review. RESULTS: A total of 439 encounters before and
      621 encounters after were evaluated including basic life support (BLS) and
      advanced life support (ALS) providers. The Before Group consisted of 408 patients
      with an average age of 61 +/- 17 years, 61.8% male. The After Group consisted of
      556 patients with an average age of 61 +/- 17 years, 58.3% male. Overall,
      combining BLS and ALS encounters, the mean CPR metric values before and after
      were: chest compression depth (5.0 cm vs. 5.5 cm; p < 0.001), rate (109.6/min vs
      114.8/min; p < 0.001), fraction (79.2% vs. 86.4%; p < 0.001), and preshock pause
      (18.8 sec vs. 11.8 sec; p < 0.001), respectively. Overall, the percent goal
      achievement before and after were: chest compression depth (48.5% vs. 66.6%; p <
      0.001), rate (71.8% vs. 71.7%, p = 0.78), fraction (68.1% vs. 91.0%; p < 0.001),
      and preshock pause (24.1% vs. 59.5%; p < 0.001), respectively. The BLS encounters
      and ALS encounters had similar statistically significant improvements seen in all
      metrics. CONCLUSION: This post-event, self-assessment CQI feedback form was
      associated with significant improvement in delivery of out-of-hospital CPR depth,
      fraction and preshock pause time.

PMID- 30118618
TI  - Economic evaluation of adolescents and adults' pertussis vaccination: A
      systematic review of current strategies.
AB  - The reemergence of pertussis in the last two decades led to the introduction of
      adolescents and adults immunization strategies of tetanus-diphtheria-acellular
      pertussis vaccines (Tdap) in several countries. The health authorities must
      consider economic aspects when deciding to recommend and fund new programs. Here
      we present a systematic review of worldwide full economic evaluations of
      pertussis vaccination targeting adolescents or adults published from 2000.
      Studies were identified by searching MEDLINE, Excerpta Medica, CRD, and Lilacs
      databases. Twenty-seven economic evaluations of different strategies with Tdap
      were identified. Booster vaccination for adolescents and adults were the most
      frequent, followed by cocooning and pregnant women vaccination. Strategies
      performance varied considerably among different studies. Assumptions regarding
      underreporting correction, herd protection and vaccine coverage were crucial to
      cost-effectiveness results. Understanding the model and the parameters used is
      essential to understand the results, and identify the major issues important to
      public health decisions.

PMID- 30118619
TI  - Therapeutic Alliance and Intervention Approach Among Acutely Suicidal Patients.

PMID- 30118621
TI  - Emergency Medical Services Utilization Is Associated With Community Deprivation
      in Children.
AB  - BACKGROUND: Pediatric emergency medical services (EMS) utilization is costly and
      resource intensive; significant variation exists across large-scale geographies.
      Less is known about variation at smaller geographic levels where factors
      including lack of transportation, low health literacy, and decreased access to
      medical homes may be more relevant. Our objective was to determine whether
      pediatric EMS utilization varied across Hamilton County, Ohio, census tracts and
      whether such utilization was associated with socioeconomic deprivation. METHODS:
      This was a retrospective analysis of children living in Hamilton County, Ohio,
      transported by EMS to the Cincinnati Children's emergency department between July
      1, 2014, and July 31, 2016. Participants' addresses were assigned to census
      tracts and an EMS utilization rate and deprivation index were calculated for
      each. Pearson's correlation coefficients evaluated relationships between tract
      level EMS utilization and deprivation. Tract-level deprivation was used as a
      predictor in patient-level evaluations of acuity. RESULTS: During the study
      period, there were 4,877 pediatric EMS transports from 219 of the 222 county
      census tracts. The county EMS utilization rate during the study period was 2.4
      transports per 100 children (range 0.2-11). EMS utilization rates were positively
      correlated with increasing deprivation (r = 0.72, 95% confidence interval [CI],
      0.65-0.77). Deprivation was associated with lower illness severity at triage,
      fewer transports resulting in resuscitation suite use, and fewer transports
      resulting in hospitalizations (all p < 0.05). CONCLUSIONS: EMS utilization varied
      substantially across census tracts in Hamilton County, Ohio. A deeper
      understanding into why certain socioeconomically deprived areas contribute to
      disproportionately high rates of EMS utilization could support development of
      targeted interventions to improve use.

PMID- 30118620
TI  - Assessment of urinary 3-indoxyl sulfate as a marker for gut microbiota diversity
      and abundance of Clostridiales.
AB  - OBJECTIVES: After allogeneic hematopoietic stem cell transplantation (allo-HCT),
      urinary levels of 3-indoxyl sulfate (3-IS) correlate with the relative abundance
      of bacteria from the class Clostridia (RAC), and antibiotic treatment is
      considered the major determinant of this outcome. A high RAC has been associated
      with favorable outcome after allo-HCT and protection from Clostridium difficile
      infection (CDI). We assessed correlations between alpha diversity, RAC and
      urinary 3-IS levels in a non-allo-HCT clinical cohort of antibiotic treated
      patients to further explore 3-IS as a biomarker of reduced diversity and
      predisposition to CDI. METHODS: Fecal and urinary specimens were analyzed from 40
      non-allo-HCT hospitalized patients before and 9 +/- 2 days after initiation of
      intravenous antibiotic treatment. Fecal microbiota were analyzed by 16s RNA
      sequencing and urinary 3-IS was analyzed by liquid chromatography-tandem mass
      spectrometry. Receiver operating characteristic (ROC) analysis was performed to
      assess the predictive value of 3-IS. RESULTS: At a RAC cutoff of <30%, the binary
      logarithm of 3-IS (medium 3-IS: <=2.5; high 3-IS: >2.5) was predictive with an
      accuracy of 82% (negative predictive value: 87%, positive predictive value 67%).
      Accuracy was improved by combing antibiotic history with 3-IS levels (accuracy
      89%, npv 88%, ppv 92%). CONCLUSION: In conjunction with patient antibiotic
      history, 3-IS is a candidate marker to predict RAC.

PMID- 30118623
TI  - Need for Affect, Interpersonal Psychological Theory of Suicide, and Suicide
      Proneness.
AB  - OBJECTIVES: The present study expands upon the Interpersonal Psychological Theory
      of Suicide (IPTS), examining its relationship with the need for affect (NFA), a
      construct explaining attitudes toward seeking both positive and negative
      emotions. METHOD: A sample of 576 emerging adults completed measures of NFA,
      IPTS, suicide proneness, and demographics online. RESULTS: Findings include NFA
      accounting for a small significant amount of suicide proneness, a positive
      association between approaching emotions and one indicator of suicide proneness,
      negative association between approaching emotions and thwarted belongingness, and
      positive associations between avoidance of emotions with both perceived
      burdensomeness and thwarted belongingness. CONCLUSION: Findings are discussed
      concerning NFA as a theoretically- and practically-relevant factor for
      understanding suicide.

PMID- 30118622
TI  - Marijuana and Prescription Pain Reliever Use among Cigarette Smokers.
AB  - Due to marijuana's analgesic effects and its growing national legal status, it is
      likely that marijuana's rising prevalence will impact prescription pain reliever
      (PPR) use. The present study investigates the relationship between marijuana and
      PPR use among U.S. adult current cigarette smokers. Data were analyzed from the
      Tobacco and Attitudes Beliefs Survey II, with 348 current cigarette smokers, aged
      24-88. Logistic regression was used to examine the likelihood of current (past 30
      days) PPR use by marijuana use (never, ever, and current) among cigarette
      smokers. Among PPR users (N = 76), we also investigated whether marijuana use
      frequency predicted current PPR use. Compared to never marijuana users,
      participants were more likely to report past 30-day PPR use if they have ever
      used marijuana (AOR: 2.58, 95% CI: 1.51-4.43) or have used marijuana in the past
      30 days (AOR: 3.38, CI: 1.76-6.49). No significant relationship was found between
      marijuana use frequency and PPR use. Thus, in this sample of adult cigarette
      smokers, past and current marijuana users were two to three times more likely to
      report PPR use than never marijuana users. These findings can help inform
      policymakers and healthcare providers in their fight against the opioid epidemic.

PMID- 30118624
TI  - The impact of LSVT BIG therapy on postural control for individuals with Parkinson
      disease: A case series.
AB  - BACKGROUND AND PURPOSE: LSVT BIG therapy may improve motor function and gait in
      those with early Parkinson disease (PD), but its impact on postural control for
      those with moderate PD has not been investigated. The purpose of this case series
      is to describe the impact of LSVT BIG therapy on postural control and gait in
      three individuals with moderate PD. INTERVENTION: Three individuals with moderate
      PD, classified as stage 3 on the Hoehn and Yahr Scale, participated in the LSVT
      BIG therapy program. Intervention included 16-18 individual physical therapy
      sessions, provided within 4 weeks, focused on increasing amplitude of movement
      and a daily home exercise program. Outcomes, including balance, gait, dual-task
      performance, quality of life, and balance confidence, were examined after program
      completion, 1- and 4-months later. OUTCOMES: Clinically meaningful improvements
      in balance and gait, including performance under dual-task conditions, were
      achieved by all patients and many of these improvements were maintained up to 4
      months later. Changes in quality of life were not observed during the length of
      the intervention. CONCLUSION: LSVT BIG therapy may improve postural control,
      gait, and dual-task performance, and therefore reduce fall risk for individuals
      with moderate PD.

PMID- 30118625
TI  - A Novel Infant Chest Compression Assist Device Using a Palm Rather Than Fingers:
      A Randomized Crossover Trial.
AB  - OBJECTIVE: We developed a novel compression assist device (palm presser) to
      perform chest compressions using a palm in infant cardiopulmonary resuscitation
      (CPR). We hypothesized that the palm presser will increase compression depth
      without increasing hands-off time and will reduce rescuer fatigue compared with
      the two-finger technique (TFT). METHODS: In this randomized crossover manikin
      trial, participants performed two minutes of CPR with a 30:2
      compression:ventilation ratio using the palm presser and the TFT in randomized
      sequence on an infant manikin. CPR parameters, including compression depth and
      hands-off time, were collected to compare CPR quality between the palm presser
      and the TFT. The linear mixed-effect model was used to control the carryover
      effect of a crossover design in the analysis of CPR parameters. To evaluate
      rescuer fatigue, we compared changes in compression depth over time and
      calculated the odds of sufficiently deep compressions over time between the two
      groups. RESULTS: The palm presser resulted in greater mean compression depth
      (41.5 +/- 1.6 mm vs. 36.8 +/- 5.5 mm, p < 0.001), greater sufficiently deep
      compressions (80.9 +/- 27.8% vs. 42.4 +/- 35.4%, p < 0.001), and better correct
      hand position (99.9 +/- 0.5% vs. 83.9 +/- 25.3%, p = 0.013) than the TFT. Total
      compressions, compression rate, total ventilations, volume of ventilations, and
      hands-off time were not significantly different between the two groups. The mean
      change in compression depth over time was greater with the TFT than with the palm
      presser (regression coefficient: -0.024 [95% CI -0.030 to -0.018] vs. -0.004 [95%
      CI -0.006 to -0.002]). The odds of a compression depth greater than 40 mm
      increased 2.8 times (95% CI 2.2 to 3.4) with the TFT during the first minute
      compared with the last minute, whereas the corresponding odds ratio when using
      the palm presser was not significantly different in the first and last minutes
      (OR: 1.2 [95% CI 0.9 to 1.5]). CONCLUSIONS: Compression with palm pressers
      resulted in greater compression depth without increasing hands-off time and
      reduced rescuer fatigue compared with compression with the TFT in simulated
      infant CPR with manikins.

PMID- 30118627
TI  - Characteristics of Frequent Users of Emergency Medical Services in Singapore.
AB  - OBJECTIVES: This study aims to describe frequent users of Emergency Medical
      Services (EMS) conveyed to a Singapore tertiary hospital, focusing on a
      comparison between younger users (age <65) and older users in diagnoses and
      admission rates. METHODS: All patients conveyed by EMS to a tertiary hospital 4
      times or more over a 1-year period in 2015 had their EMS ambulance charts and
      Emergency Department (ED) electronic records retrospectively analyzed (n = 243),
      with admission the primary outcome. RESULTS: The 243 frequent users were analyzed
      with a combined total of 1,705 visits, out of a total of 10,183 patients with
      12,839 visits conveyed by EMS to Singapore General Hospital (SGH) in 2015.
      Younger frequent users (<65 years age) were found to be predominantly male
      (79.6%, p = 0.001) and were on average responsible for more visits than elderly
      frequent users (8.6 vs. 5.7, p = 0.004). Medical co-morbidities were
      significantly more prevalent in older users. Younger frequent users were more
      likely to be smokers (60.2% vs. 22.3%), heavy drinkers (51.3% vs. 8.5%),
      substance abusers (12.4% vs. 0.8%), and bad debtors (49.6% vs. 20.0%, p < 0.001).
      A larger proportion presented with altered mental states (11.7% vs. 5.4%, p <
      0.001) and alcohol related diagnoses (34.7% vs. 5.3%, p < 0.001). Many were
      picked up from public areas (45.5% vs. 19.6%, p < 0.001), and had lower acuity
      triage scores at both EMS (p < 0.001) and ED (p = 0.001). They had lower
      admission rates (40.5% vs. 78.7%, p < 0.001) and shorter length of stay (4.3 vs.
      5.9 days, p < 0.001). Univariable and multivariable analysis showed alcohol
      related diagnoses, history of alcohol abuse and lower triage scores were less
      likely to require admissions. CONCLUSION: Frequent EMS users consume a
      disproportionate amount of healthcare resources. Two broad subgroups of patients
      were identified: younger patients with social issues and older patients with
      multiple medical conditions. EMS usage by older patients was significantly
      associated with higher rates of admission.

PMID- 30118626
TI  - SGLT2 knockout prevents hyperglycemia and is associated with reduced pancreatic
      beta-cell death in genetically obese mice.
AB  - Inhibition of the sodium-glucose co-transporter type 2 (SGLT2) has received
      growing acceptance as a novel, safe and effective means to improve glycemic
      control in patients with type 2 diabetes. Inhibition of SGLT2 lowers the renal
      glucose threshold and reduces plasma glucose by promoting glucose excretion in
      urine. Both animal studies and clinical trials in man suggest that SGLT2
      inhibition has the potential to improve pancreatic beta-cell function by reducing
      glucose toxicity. However, there is limited data exploring how reducing
      glucotoxicity via SGLT2 inhibition affects rates of beta-cell proliferation and
      death throughout life in the context of insulin resistance and type 2 diabetes.
      SGLT2-/- mice were backcrossed to the db/db strain to produce littermate control
      db/db-SGLT2+/+ and experimental db/db-SGLT2-/- mice. Mice were euthanized at 5,
      12 and 20 weeks of age to collect plasma for glucose, insulin, lipid and cytokine
      measures, and pancreata for histological analysis including determination of beta
      cell mass and rates of proliferation and death. SGLT2 deletion in db/db mice
      reduced plasma glucose as early as 5 weeks of age and continued throughout life
      without changes in plasma lipids or cytokines. Reduced plasma glucose levels
      occurred in parallel with an increase in the relative beta-cell volume and
      reduced frequency of beta-cell death, and no apparent change in rates of beta
      cell proliferation. These data add to a growing body of evidence demonstrating
      that improved glycemic control achieved through SGLT2 inhibition can preserve
      beta-cell function and endogenous insulin secretion by reducing glucose toxicity
      and rates of beta-cell death.

PMID- 30118628
TI  - Identifying Typologies of Persons Who Died by Suicide: Characterizing Suicide in
      Victoria, Australia.
AB  - The objective of the study was to determine whether people who died by suicide
      form groups based on demographic, psychosocial, mental and physical health
      factors and exposure to stressors. A retrospective case series review of 2,839
      individuals who died by suicide in Victoria, Australia over the period 2009-2013
      was conducted. A two-stage cluster analysis was performed. Diagnosis of mental
      illness was present in 52% of cases and initial cluster analysis determined two
      groups with the main predictor of group membership being the presence of
      diagnosed mental illness. Further analysis identified four subgroups within the
      mental illness group and two within the non-mental illness group. The study
      demonstrates that suicide does not always occur in the context of mental illness;
      people who die by suicide cannot be considered a homogenous group.

PMID- 30118629
TI  - Workplace Incivility Among Nationally Certified EMS Professionals and
      Associations with Workforce-Reducing Factors and Organizational Culture.
AB  - BACKGROUND: Incivility, defined as negative interpersonal acts that violate
      workplace and social norms, has been linked to negative outcomes in healthcare
      settings. A minimal amount is known regarding workplace incivility among
      emergency medical services (EMS) professionals. Our objectives were to (1)
      evaluate the prevalence of incivility and factors associated with experiencing
      workplace incivility; (2) describe the association between incivility and
      workforce-reducing factors (stress, career satisfaction, turnover intentions, and
      workplace absences); and (3) quantify the association between incivility and the
      organizational culture of an EMS agency. METHODS: A random sample of 38,000
      nationally-certified EMS professionals received an electronic questionnaire with
      an EMS-adapted Workplace Incivility Scale, the Competing Values Framework
      organizational culture scale, and factors that may negatively impact the EMS
      workforce. All completed surveys from nonmilitary EMS professionals currently
      providing patient care at the EMT level or higher were included in these
      analyses. We constructed multivariable logistic regression models (OR, 95% CI) to
      identify factors associated with experiencing workplace incivility and to examine
      the associations between experiencing incivility and workforce-reducing factors.
      We calculated univariable odds ratios to assess the association between
      organizational culture type and incivility. RESULTS: A total of 3,741 EMS
      professionals responded to the survey (response rate =10.3%), with 2,815 (75.2%)
      meeting inclusion criteria. Incivility from supervisors or coworkers was
      experienced at least once a week by 47.4% of respondents. Factors associated with
      increased odds of experiencing incivility included female sex, AEMT/paramedic
      certification level, increasing years of EMS experience, service types other than
      9-1-1 response, and higher weekly call volumes. Exposure to regular incivility
      was associated with increased odds of dissatisfaction with EMS, a main EMS job or
      a main supervisor; moderate or higher stress levels; intent to leave one's job
      and EMS in the next 12 months; and 10 or more workplace absences in the past 12
      months. The organizational culture type "market" was associated with the greatest
      odds of incivility. CONCLUSIONS: Nearly half of respondents experienced
      incivility once a week or more, and incivility was associated with potential
      workforce-reducing factors. Further research is needed to understand how
      organizational climate and interpersonal behaviors in the workplace affect the
      EMS workforce.

PMID- 30118630
TI  - Correlation between meteorological parameters and nitrogen compounds present in
      wastewater in the formation of nitrous oxide in soils.
AB  - In the present work, nitrous oxide emissions were estimated [mg/L] by the use of
      lysimeters under the closed chamber technique for a six month period. The
      lysimeters were classified by the type of irrigation used: one for drinking
      water, and the other for treated wastewater. Each lysimeter had two different
      types of soil (sand and clay), based on the types of soil in Chihuahua City,
      Mexico. An additional classification based on the depth was done (reticular and
      vadose zone). Each zone collected gas by the use of a closed chamber technique,
      allowing the samples to be taken for subsequent quantification and analysis by
      gas chromatography. A statistical analysis of variance (ANOVA) and principal
      components analysis (PCA) were conducted to identify the most influential
      variables or parameters in the formation of nitrous oxide. The variables that
      were considered for analysis were total Kjeldahl nitrogen (TKN), ammoniacal
      nitrogen (NH3-N), nitrate nitrogen (NO3-N), and nitrite nitrogen (NO2-N), along
      with meteorological parameters. In total, 58944 mg/L of N2O were emitted during
      the measurement period. The results showed that concentration emissions of N2O
      where the type of soil is sandy were smaller than those of clay soil, while the
      mean concentration in the vadose zone was higher than those in the reticular
      zone, regardless the type of soil. The parameters that showed greater influence
      in the N2O emissions were NO2-N and NO3-N concentrations. Temperature also played
      an important role in the emissions (the highest emissions were emitted during the
      cold months). Furthermore, denitrification appeared to be the dominant process in
      the production of nitrous oxide in soils. Implications: Nitrous oxide (N2O)
      emissions produced in lysimeters with two types of soil (sand and clay) at two
      different depths (vadose and reticular zones) using treated waste water showed
      that the higher emissions of N2O are derived from clay soils in vadose zone; it
      could be due to the formation of clogging that favors the formation of anoxic
      conditions for the denitrification process. The parameters that showed more
      influence in the N2O emissions were nitrite (NO2-N) and nitrate (NO3-N)
      concentrations along with the temperature.

PMID- 30118631
TI  - Soldiers and Leaders With Combat Experience: Unit Health and Climate.
AB  - OBJECTIVE: The present study investigated the association between previous
      deployment experience and somatic symptoms, mental health, unit climate
      perceptions, anger, and risk taking among junior-enlisted soldiers who were
      preparing to deploy or who were in garrison, or home duty station. The study also
      investigated potential differences in these variables based on unit leader
      deployment history. METHOD: Soldiers in a combat unit were surveyed either in a
      predeployment (n = 1,554; one week before deployment) or garrison setting (n =
      1,326). Surveys addressed deployment history, health, unit climate, and leader
      deployment history. RESULTS: Those in the predeployment sample with deployment
      history had significantly more somatic symptoms, posttraumatic stress disorder
      (PTSD), sleep problems, and anger reactions, and significantly less favorable
      unit climate perceptions, compared to those without deployment history. Higher
      rates of sleep problems, anger reactions, and endorsement of a risk-taking item,
      along with less favorable unit climate perceptions, were also reported by
      experienced soldiers in the garrison sample. In both samples, soldiers with
      experienced leaders endorsed more risk-taking behaviors than those with
      inexperienced leaders. Predeployment soldiers with experienced leaders also
      reported higher unit cohesion than those with inexperienced leaders. CONCLUSIONS:
      Previous deployments appear to increase the risk for a range of outcomes reported
      by soldiers at predeployment and in garrison. Findings suggest the impact of
      deployment should be considered well beyond the traditional deployment phases.
      Future research should examine what experienced leaders bring to units, in terms
      of boosting cohesion and potentially increasing the willingness of unit members
      to engage in risk-taking behaviors.

PMID- 30118632
TI  - Profiles of Risk for Suicidal Behavior in Past and Current United States Military
      Personnel: Latent Profile Analysis of Current Risk Factors.
AB  - Person-centered approaches are underutilized to identify people with shared risk
      profiles. In this study, an at-risk sample of 773 past/current military personnel
      (Mage = 31.3 years, SD = 6.8) with current ideation (90.6%) and/or a prior
      suicide attempt (43.9%) were assessed using latent profile analysis. Variables
      included prior suicide attempts, suicidal ideation, alcohol/drug use, insomnia,
      depression, belongingness, burdensomeness, and post-traumatic stress disorder
      symptoms. Three classes emerged: Low Symptoms (N = 502), Elevated Suicidality (N
      = 176), and Elevated Substance Use (N = 95). At 1-month follow-up, the Elevated
      Suicidality and Elevated Substance Use classes had the highest odds of suicidal
      behavior. The finding concerning the Elevated Substance Use class suggests it may
      represent a distinct short-term risk group in military personnel.

PMID- 30118633
TI  - Long-term antibody persistence against hepatitis B in adolescents 14-15-years of
      age vaccinated with 4 doses of hexavalent DTPa-HBV-IPV/Hib vaccine in infancy.
AB  - We evaluated antibody persistence against hepatitis B virus (HBV) in adolescents
      previously vaccinated with a hexavalent diphtheria-tetanus-acellular pertussis
      HBV-inactivated poliovirus-Haemophilus influenzae type b conjugate vaccine (DTPa
      HBV-IPV/Hib), as part of the national newborn immunization program in Germany. We
      also assessed the anamnestic response to a challenge dose of a monovalent HBV
      vaccine. In this phase 4, open-label, non-randomized study (NCT02798952), 302
      adolescents aged 14-15 years, primed in their first 2 years of life with 4 DTPa
      HBV-IPV/Hib doses, received one challenge dose of monovalent HBV vaccine. Blood
      samples were taken before and one month post-vaccination and used to determine
      antibody levels against hepatitis B surface antigen (HBs). Reactogenicity and
      safety were also assessed post-challenge dose. Pre-challenge dose, 53.7% of 268
      participants included in the according-to-protocol cohort for immunogenicity had
      anti-HBs antibody concentrations >=10 mIU/mL (seroprotection cut-off) and 16.8%
      had anti-HBs antibody concentrations >=100 mIU/mL. One month post-challenge dose,
      93.3% of adolescents had anti-HBs antibody concentrations >=10 mIU/mL and 87.3%
      had antibody concentrations >=100 mIU/mL. An anamnestic response was mounted in
      92.5% of adolescents. Injection site pain (in 33.6% of participants) and fatigue
      (30.2%) were the most frequently reported solicited local and general symptoms,
      respectively. Six of the 55 unsolicited adverse events reported were considered
      vaccination-related. Two vaccination-unrelated serious adverse events were
      reported during the study. Long-term antibody persistence against hepatitis B was
      observed in 14-15 years old adolescents previously primed in infancy with DTPa
      HBV-IPV/Hib. A challenge dose of monovalent HBV vaccine induced strong anamnestic
      response, with no safety concerns.

PMID- 30118634
TI  - Attachment and non-suicidal self-injury among young adolescents: The indirect
      role of behavioral problems.
AB  - OBJECTIVE: Non-suicidal self-injury (NSSI) often occurs before age 15, yet the
      majority of research on risk factors for this dangerous behavior has focused on
      older samples. Insecure attachment has been previously identified as a risk
      factor for both NSSI and behavioral problems, and behavioral problems appear to
      be particularly associated with NSSI among young populations. Redressing the lack
      of young adolescent NSSI research, the present study uses longitudinal data from
      a sample of young adolescents to test a model in which insecure attachment acts
      as a prospective risk factor for NSSI via emotional and behavioral problems.
      METHODS: Data on NSSI, child-mother attachment, and emotional and behavioral
      problems were collected from 559 (41.1% male) Flemish adolescents when they were
      13 years old (M = 12.71, SD = 0.32), and again one year later. Insecure
      attachment was measured using maternal items on the Experiences in Close
      Relationships - Revised Child scale. Psychological adjustment was assessed with
      the Strengths and Difficulties Questionnaire. RESULTS: We found that anxious and
      avoidant attachment were indirectly associated with NSSI through behavioral
      problems but not through emotional problems. CONCLUSIONS: Findings highlight the
      role of behavioral problems as a risk factor for NSSI in early adolescence, a
      rarely studied developmental period during which NSSI often first starts.
      Findings suggest that one possible pathway for the attachment-NSSI association
      among young adolescents is through behavioral problems. Therapies that improve
      child-parent attachment may reduce NSSI among young adolescents both directly,
      and indirectly by improving behavioral problems.

PMID- 30118635
TI  - Healthy elderly and influenza vaccination.
AB  - In many countries, those at risk for complications due to influenza are invited
      for influenza vaccination, to prevent serious consequences for themselves and
      those around them. However, vaccination rates are decreasing. The first
      invitation for vaccination may provide an opportunity to convey ample information
      about the (dis)advantages of vaccination. We aimed to identify subgroups less
      likely to be vaccinated after their first invitation. Using data from 87 general
      practices participating in NIVEL Primary Care Database, we selected persons
      invited for vaccination for the first time because of their 60th birthday. Of
      3.238 included persons, 78% were not vaccinated after their first invitation and
      in the vast majority (84%) this decision remained consistent over the next years.
      Men and those with fewer GP contacts were less likely to be vaccinated. This
      latter group is not easily reached by the GP, so maybe other ways should be
      considered to convey information about influenza vaccination.

PMID- 30118636
TI  - "What next now that you are sixty?" - Preliminary exploration of the self
      reported aspirations of community-dwelling older persons in the Western Cape
      Province, South Africa within the active aging framework.
AB  - Future aspirations of older persons should interest professionals involved in
      health promotion services in view of World Health Organization's Active Aging
      Framework. With the South African government's plan to raise life expectancy to
      70 years by 2030, there is likelihood that life expectancy at 60 years will
      increase. Future aspirations give motivations for living, with short and long
      term goals to work toward. As part of a larger study exploring the profile of
      members of 35 Service Centers for Older Persons in the Western Cape Province,
      selected using stratified random sampling, this manuscript reports on the
      qualitative responses relating to the self-determined future aspirations of the
      members. Thematic analysis was utilized to explore the aspirations of 625
      members, aged 60-100 years. The aspirations were classified into two, namely
      aspirations with and without possible future-oriented behavior. Separate six and
      three themes were identified respectively in the first and second categories of
      aspirations. Being members of centers meant to provide programs to enhance their
      future, an awareness of the future aspirations of older persons should inform the
      services provided to encourage older persons identify something to live for.

PMID- 30118637
TI  - Trends in Prehospital Analgesia Administration by US Forces From 2007 Through
      2016.
AB  - BACKGROUND: Tactical Combat Casualty Care (TCCC) guidelines regarding prehospital
      analgesia agents have evolved. The guidelines stopped recommending intramuscular
      (IM) morphine in 1996, recommending only intravenous (IV) routes. In 2006, the
      guidelines recommended oral transmucosal fentanyl citrate (OTFC), and in 2012 it
      added ketamine via all routes. It remains unclear to what extent prehospital
      analgesia administered on the battlefield adheres to these guidelines. We seek to
      describe trends in analgesia administration patterns on the battlefield during
      2007-2016. METHODS: This is a secondary analysis of a Department of Defense
      Trauma Registry data set from January 2007 to August 2016. Within that group, we
      searched for subjects who received IM morphine, IV morphine, OTFC, parenteral
      fentanyl, or ketamine (all routes). RESULTS: Our predefined ED search codes
      captured 28,222 subjects during the study period. Of these, 594 (2.1%) received
      IM morphine; 3,765 (13.3%) received IV morphine; 589 (2.1%) received OTFC; and
      1,510 (5.4%) subjects received ketamine. Annual rates of administration of IM
      morphine were relatively stable during the study period, while those for OTFC and
      ketamine generally trended upward starting in 2012. In particular, the proportion
      of subjects receiving ketamine rose from 3.9% (n = 995/25,618) during the study
      period preceding its addition to the TCCC guidelines (2007 to 2012) to 19.8%
      thereafter (2013-2016, n = 515/2,604, p < 0.001). CONCLUSIONS: During the study
      period, rates of prehospital administration of IM morphine remained relatively
      stable while those for OTFC and ketamine both rose. These findings suggest that
      TCCC guidelines recommending the use of these agents had a material impact on
      prehospital analgesia patterns.

PMID- 30118638
TI  - Center of pressure-based balance evaluation in individuals with Parkinson's
      disease: a reliability study.
AB  - OBJECTIVE: The purpose of this study was to assess the test-retest reliability of
      different balance task outcomes, based on center of pressure (COP) measures in
      individuals with Parkinson's disease. METHOD: In this cross-sectional study, 19
      older individuals with idiopathic Parkinson's disease (seven females, 71 +/- 7.8
      years) performed a set of seven balance tasks on two occasions (a week apart) on
      an electronic force platform. Each set consisted of: 1) Bipedal; 2) Romberg with
      open eyes (OE); 3) Romberg with closed eyes (CE); 4) Tandem with OE; 5) Tandem
      with CE; 6) Tandem with OE using a dual task (DT) condition (simple mathematic
      operations concomitant with testing); and 7) One-leg stance, with the leg of
      preference over the force platform, with OE. The test-retest reliability of COP
      measures was tested using intraclass correlation coefficient (ICC) and Bland
      Altman plots. RESULTS: The ICC results for the different tasks showed that the
      most reliable para- meters were derived from a 95% confidence ellipse around the
      COP and mean velocity, with the most reliable task being the Romberg with CE.
      CONCLUSIONS: We confirmed that balance based on COP measures was reliable in
      individuals with Parkinson's disease, especially during the Romberg condition
      with closed eyes.

PMID- 30118639
TI  - Impact of Lift Assist Calls on Paramedic Services: A Descriptive Study.
AB  - INTRODUCTION: The aging population in Canada is steadily increasing and is
      placing greater demand on paramedic services, especially through the growing
      number of non-emergent lift assist (LA) calls. A LA occurs when a person calls
      paramedic services and requests assistance to get up or mobilize, usually after
      experiencing a fall. The patient refuses transport to the emergency department
      for further medical attention. LA calls are time consuming and are non
      reimbursable. The increase in number of this call type, specifically amongst
      older adults, is placing strain on paramedic services. OBJECTIVES: The purpose of
      this study was to describe the characteristics of LA calls in patients aged 65
      and older and determine their impact on paramedic services. METHODS: A dataset of
      1,121 LA calls of patients aged 65 and older was extracted from Middlesex-London
      Emergency Medical Services (MLEMS) database of electronic patient care reports
      collected over 1 year in 2015. Statistical and qualitative analyses were
      performed to describe LAs, perform time analysis, and extract dominant themes
      from the text in report notes written by paramedics. RESULTS: The LA calls were
      generated from 611 individuals: 334 women (54.7%) and 275 men (45%), of which 192
      (32%) individuals called more than one time. On average, a LA call lasted 43
      minutes and ranged from 6 minutes to 2 hours and 23 minutes. In 2015, paramedics
      spent 801 hours, or the equivalent of 33 days (24 hours/day), solely conducting
      LAs for older adults. Text analysis determined that the bedroom (24.9%) and
      bathroom (17.0%) were the most common locations where LAs occurred. Most
      frequently, LAs were caused by a collapse or drop (28.7%), slide (25.7%), slip
      (16.7%), or trip (11.7%). CONCLUSION: LAs consume the time of paramedics,
      preventing them from responding to more urgent emergency calls. Alternative
      solutions are needed to reduce the negative impact of LAs on paramedic services.

PMID- 30118640
TI  - GPS Devices in a Simulated Mass Casualty Event.
AB  - OBJECTIVE: The aim of this study was to assess the staff perception of a global
      positioning system (GPS) as a patient tracking tool at an emergency department
      (ED) receiving patients from a simulated mass casualty event. METHODS: During a
      regional airport disaster drill a plane crash with 46 pediatric patients was
      simulated. Personnel from airport fire, municipal fire, law enforcement,
      emergency medical services, and emergency medicine departments were present.
      Twenty of the 46 patient actors required transport for medical evaluation, and we
      affixed GPS devices to 12 of these actors. At the hospital, ED staff including
      attending physicians, fellows and nurses working in the ED during the time of the
      drill accessed a map through an application that provided real-time geolocation
      of these devices. The primary outcome was staff reception of the GPS device as
      assessed via Likert scale survey after the event. The secondary outcomes were
      free text feedback from staff and event debriefing observations. RESULTS: Queried
      registered nurses, attending physicians, and pediatric emergency medicine fellows
      perceived the GPS device as an advantage for patient care during a disaster. The
      GPS device allowed multiple-screen real-time tracking and improved situational
      awareness in cases with and without EMS radio communication prior to arrival at
      the hospital. CONCLUSION: ED staff reported that the use of GPS trackers in a
      disaster improved real-time tracking and could potentially improve patient
      management during a mass casualty event.

PMID- 30118641
TI  - Bilateral deafness two days following influenza vaccination: a case report.
AB  - OBJECTIVE: We report a case of deafness occurring in a temporal context of an
      influenza vaccination in a 79-year-old woman. METHODS: Case report and review of
      the literature on influenza causing deafness. RESULTS: A 79-year-old woman with
      normal hearing developed acute bilateral sensorineural hearing loss two days
      after a seasonal influenza vaccination, other obvious reasons for acute hearing
      loss were excluded. CONCLUSION: This patient appears to be the first reported
      case of bilateral deafness following a trivalent seasonal influenza vaccination.

PMID- 30118642
TI  - Videographic Assessment of the Quality of EMS to ED Handoff Communication During
      Pediatric Resuscitations.
AB  - BACKGROUND: The National Association of Emergency Medical Services (EMS)
      Physicians emphasizes the importance of high quality communication between EMS
      providers and emergency department (ED) staff for providing safe, effective care.
      The Joint Commission has identified ineffective handoff communication as a
      contributing factor in 80% of serious medical errors. The quality of handoff
      communication from EMS to ED teams for critically ill pediatric patients needs
      further exploration. OBJECTIVE: This study assessed the quality of handoff
      communication between EMS and ED staff during pediatric medical resuscitations.
      METHODS/DESIGN: We conducted a retrospective review of video recordings of
      pediatric patients who required critical care ("resuscitation") in the ED between
      January 2014 and February 2016 at a Level 1 pediatric trauma center. Handoff
      quality between EMS and emergency department teams was assessed for completeness,
      timeliness, and efficiency. Institutional review board approval was obtained.
      RESULTS: Sixty-eight resuscitations were reviewed; 28% presented in cardiac
      arrest, requiring cardiopulmonary resuscitation (CPR). Completeness of
      information communicated was variable and included chief complaint (88%),
      prehospital interventions (81%), physical exam findings (63%), medical history
      (59%), age (56%), and weight (20%). Completeness of specific vital sign reporting
      included: respiratory rate (53%), heart rate (43%), oxygen saturation (39%), and
      blood pressure (31%). Timeliness of communication included median patient handoff
      and report times of 50 seconds [IQR 30,74] and 108 seconds [IQR 62,252],
      respectively. Inefficient communication occurred in 87% of handoffs, including
      interruptions by ED staff (51%), questions from the ED physician team leader
      asking for information already communicated (40%), and questions by ED physician
      team leader requesting information not yet communicated (65%). When comparing non
      CPR to CPR cases, only timeliness of patient handoff was significantly different
      for those patients receiving prehospital CPR. CONCLUSION: Handoff communication
      between EMS and ED teams during pediatric resuscitation was frequently incomplete
      and inefficient. Future educational and quality improvement interventions could
      aim to improve the quality of handoff communication for this patient population.

PMID- 30118643
TI  - Dualism, Tension, and Integration: Dialectics as a Theme of Integration in Daily
      Lives of Israeli Gay Men Who Became Fathers Through Overseas Surrogacy.
AB  - This article explores the constructed meanings of lived experiences of Israeli
      gay men who became parents through commercial overseas surrogacy. Based on the
      analysis of 39 in-depth, semistructured interviews with gay fathers, we show that
      their parenting experiences are shaped in contradictory ways, allowing them to
      adopt a reflective position in relation to existing social frameworks. Data from
      in-depth interviews reveal three major themes. The first refers to the gap
      between biogenetic and social concepts of parenthood and kinship. The second
      presents the dialectics between continuity and change that gay parenthood
      exhibits. The third theme focuses on the impact of these contradictions on gay
      parents' identities and the construction of autonomy concepts in their lives. By
      doing so, we highlight the importance of tensions and contradictions in shaping
      the daily living experiences of gay parents, as well as the importance of
      dialectics in promoting gay parents' integration within heteronormative society.

PMID- 30118644
TI  - Evaluation of a Brief Suicide Prevention Training Program for College Campuses.
AB  - OBJECTIVE: Suicide is the second leading cause of death in college students.
      While research indicates a positive impact of gatekeeper training programs on
      knowledge and attitudes, few have examined change in suicide prevention
      behaviors. The purpose of the study was to evaluate the effects of a brief
      suicide prevention training for college campuses on knowledge, self-efficacy to
      intervene, and gatekeeper behaviors. METHOD: A longitudinal design was employed
      to examine changes from pretest to post-test and three-month follow-up.
      Participants included 517 students, staff, and faculty who attended a 90 minute
      training and completed self-report surveys. The training included both didactic
      and experiential components. RESULTS: Repeated measures ANOVAs indicated that
      knowledge, self-efficacy to discuss suicide and to refer to resources, and
      gatekeeper behavior increased from pretest to post-test and follow-up. Students
      exhibited a greater increase in gatekeeper behaviors, in comparison to non
      students. Large changes were observed on publicizing suicide prevention
      information and having informal conversations about suicide with students, and
      76% had engaged in gatekeeper behavior at follow-up. CONCLUSIONS: Findings offer
      support for the potential efficacy of a brief prevention program, with promising
      effects on several suicide prevention behaviors. Declines on knowledge and self
      efficacy from post-test to follow-up highlight the importance of booster sessions
      and complementary programing.

PMID- 30118645
TI  - Anatomy of the Mediterranean Diet and Mortality Among Older Women with Frailty.
AB  - We examined individual components of the Mediterranean Diet (Med) and evaluated
      their relative contribution to mortality rates in older women with frailty. A
      sample (N = 10,431) included Women's Health Initiative Observational Study
      participants aged 65-84 y with complete frailty diagnostic criteria and dietary
      data. Frailty was assessed with modified Fried's criteria, and dietary data were
      collected through food frequency questionnaire. Over a mean follow-up of 12.4 y
      (range 3-21.0), 3,259 (31.2%) deaths occurred. Crude death rates demonstrated a
      decrease in mortality with higher intake of individual Med components. However,
      in the mutually adjusted models, most Med components on their own were not
      significantly associated with mortality. Exceptions were vegetables, nuts, and
      whole grains. A higher intake of vegetables, nuts, and whole grains were
      associated with a significantly decreased hazard of mortality, by 9% (P = 0.02),
      13% (P < 0.001), and 17% (P < 0.001), respectively. The relative contribution of
      these components to diet mortality associations were 21%, 42%, and 57% for
      vegetables, nuts, and whole grains, respectively. Subgroup analyses by chronic
      morbidity, smoking status, or excluding women with early death did not
      substantially change these results.

PMID- 30118647
TI  - Self-Neglect in Older Populations: A Description and Analysis of Current
      Approaches.
AB  - Self-neglect in old age has severe effects on a person's health and quality of
      life and poses diverse challenges for primary caregivers and the community. The
      authors provide a narrative overview of the literature on self-neglect and
      summarize what is known to date about the main approaches for describing self
      neglect, the factors that contribute to self-neglect, and the interventions that
      have been attempted. We found that answering the question about what factors led
      people into a state of self-neglect was extremely complex since many studies
      described a variety of interlinked factors, some of which are sociocultural and
      others medical. Our analysis suggested a need for a consolidated approach that
      focuses instead on the vulnerabilities affecting an older person and the factors
      that can improve resilience to adversity. Tackling vulnerability and resilience
      may hold the keys to successful multidisciplinary and person-centered management
      of self-neglect in older age.

PMID- 30118648
TI  - Next-generation sequencing reveals mutational accordance between cell-free DNA
      from plasma, malignant pleural effusion and ascites and directs targeted therapy
      in a gastric cancer patient.
AB  - Cell-free DNA (cfDNA) has been a research hotspot in molecular tumor profiling.
      In advanced gastric cancer patients, malignant pleural effusion (MPE) and ascites
      provide a wealth of tumor cells that can be investigated. Here we conducted next
      generation sequencing (NGS) on matched cfDNA from plasma, MPE and ascites from a
      stage-IV gastric cancer patient to identify potential therapeutic targets. In all
      three samples, we detected an amplification in the cellular-mesenchymal to
      epithelial transition factor (MET) gene, a truncation mutation in SMAD3
      (p.R368X), and four ataxia telangiectasia-mutated gene (ATM) variants, including
      a missense mutation (p.E2351A), an in-frame deletion (p.NPAVIM2353delinsK), a
      frame-shift deletion (p.D1758fs) and an ATM- BPI fold containing family B member
      1 (BPIFB1) gene fusion. In contrast, we detected amplification of TEK only in
      malignant ascites. The patient was subjected to Crizotinib to counter MET
      amplification. Our study demonstrates high accordance in mutational spectra of
      matched cfDNA from plasma, MPE and ascites, and suggests that it is feasible to
      utilize these tumor sources in clinical decision-making.

PMID- 30118646
TI  - The protective role of melatonin in chemotherapy-induced nephrotoxicity: a review
      of non-clinical studies.
AB  - BSTRACT Introduction: The aim of this study was to investigate the potential role
      of melatonin in the prevention of chemotherapy-induced nephrotoxicity at the
      preclinical level. Areas to be covered: To illuminate the possible role of
      melatonin in preventing chemotherapy-related nephrotoxicity, Preferred Reporting
      Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. A
      comprehensive search strategy was developed to include PubMed, Web of Science,
      Scopus, and Embase electronic databases from their inception to May 2018. Based
      on a set of prespecified inclusion and exclusion criteria, 21 non-clinical
      articles were ultimately included in the study. Expert opinion: Our findings
      clearly demonstrate that melatonin has a protective role in the prevention of
      chemotherapy-induced nephrotoxicity which may be caused by different chemotherapy
      agents such as cyclophosphamide, cisplatin, doxorubicin, methotrexate,
      oxaliplatin, etoposide, and daunorubicin. On the basis of current review of non
      clinical studies, this protective effect of melatonin is attributed to different
      mechanisms such as reduction of oxidative stress, apoptosis, and inflammation.
      The findings presented in this review are based on non-clinical studies and thus
      conducting appropriate clinical trials to evaluate the real effectiveness of the
      concurrent use of chemotherapy agents with melatonin in the cancer patients is
      necessary.

PMID- 30118649
TI  - Systematic Exploration of Countertransference Phenomena in the Treatment of
      Patients at Risk for Suicide.
AB  - Despite its critical role in clinical suicidology, empirical evidence on the
      nature of countertransference (CT) to patients at risk for suicide (PRS) is
      lacking. This study aimed to provide a systematic description of CT phenomena to
      PRS. Psychiatrists, psychologists and psychotherapists completed the Therapist
      Response Questionnaire (TRQ) online, with reference to a PRS. Factor analysis (n
      = 267) yielded a seven-factor structure, including 1) entrapped/rejecting, 2)
      fulfilled/engaging, 3) aroused/reacting, 4) informal/boundary crossing, 5)
      protective/overinvolvement, 6) ambivalent/inconsistent, and 7)
      mistreated/controlling. On average, clinicians reported that CT dimensions tended
      to not apply to them, except for the positively connoted factor. Our findings
      suggest that patients at risk for suicide elicit specific dimensions of CT. We
      offer two alternative interpretations of clinicians' CT endorsement patterns.

PMID- 30118650
TI  - Age of Onset of Alcohol Consumption and Subsequent Negative Health Outcomes in
      Gay and Bisexual Men Who Have Sex With Men.
AB  - The correlation between current alcohol use and sexual risk behaviors among men
      who have sex with men (MSM) is well documented, but little is known about age of
      drinking onset and current risks among this population. Data from a 2008 Internet
      survey of 8,452 MSM in the United States were used to assess factors associated
      with age of onset of alcohol use. In a multivariable model, drinking onset before
      age 15 was significantly associated with a higher number of lifetime male anal
      sex partners and being behaviorally bisexual in the past 12 months. Men who
      reported depressive symptoms in the past two weeks or who screened positive for
      alcohol abuse in the past 60 days were more likely to have early age of drinking
      onset. Findings suggest the need for targeting younger adolescents for alcohol
      screening, particularly sexual minority youth, to prevent risk behaviors in
      adulthood.

PMID- 30118651
TI  - 'Call me if you need': Social support experiences under economic and social
      change.
AB  - Social interactions play an important role in people's life and people's health
      but their scope and intensity tend to decrease with age, challenging social
      support dynamics and increasing the risk of social isolation and helplessness. In
      Portugal, policymakers still seem to rely on traditional social relations in
      eldercare, while contextual changes and trends are redefining family roles and
      behaviors and defying the established social support structure. In this work, we
      aim to examine the scope, structure and experiences of the informal social
      support network available in the country for stroke patients 6 months after their
      discharge from the acute care unit in the context of a larger study. The results
      seem to confirm the importance of family as a source of social support and shed
      light on different bonding experiences with non-kin social groups, such as
      neighbors and friends. A coordinated care provision, combining formal and
      informal support is vital and beneficial for patients, their caregivers and the
      care system.

PMID- 30118652
TI  - A comparison of urban and non-urban African American older adults on health
      related characteristics.
AB  - Although residential geographic health disparities have been noted in the
      previous literature, studies are specifically lacking on intra-group health
      comparisons of African American older adults by residential geography. The
      purpose of this study was to determine if health-related characteristics of
      African American older adults varied by residential geography. Socioeconomic
      demographics, medical conditions, primary care use, and self-ratings of general
      health, social activity, and physical activity were compared in a community
      dwelling sample of 327 urban and non-urban African American older adults. Urban
      and non-urban African American older adults were compared on health-related
      factors. Compared to urban African American older adults, those in non-urban
      areas had lower incomes, lower self-ratings of general health, social activity,
      and physical activity, and a higher frequency of arthritis and
      gastroenterological and urological conditions. Despite poorer general health and
      medical conditions, non-urban African American older adults were less likely to
      visit the doctor when needed. Study findings suggest residential geography may be
      an underappreciated underlying contributing factor to inter-group health
      disparities between African American and white older adults and not race alone.
      Therefore, social workers in public health, health care, and clinical settings
      should be aware of the interaction between race and residential geography.

PMID- 30118653
TI  - Prevalence of hepatitis C among dock workers.

PMID- 30118654
TI  - Secular trends of candidemia at a Brazilian tertiary care teaching hospital.
AB  - BACKGROUND: Candidemia is the most frequent invasive fungal disease in
      hospitalized patients, and is associated with high mortality rates. The main
      objective of this study was to evaluate changes in the epidemiology of candidemia
      at a tertiary care hospital in a 21-year period. METHODS: We evaluated all
      episodes of candidemia diagnosed between 1996 and 2016 at a University-affiliated
      tertiary care hospital in Brazil. We arbitrarily divided the study period in 3:
      1996-2002 (period 1), 2003-2009 (period 2) and 2010-2016 (period 3). Incidence
      rates were calculated using hospital admissions as denominator. RESULTS: We
      observed 331 episodes of candidemia. The incidence was 1.30 episodes per 1000
      admissions, with no significant change over time. Candida albicans (37.5%), C.
      tropicalis (28.1%), C. parapsilosis (18.4%) and C. glabrata (6.9%) were the most
      frequent species. The proportion of patients receiving treatment increased
      (65.5%, 79.4% and 74.7% in periods 1, 2 and 3, respectively, p = 0.04), and the
      median time from candidemia to treatment initiation decreased from 4 days in
      period 1 (range 0-32 days) to 2 days in period 2 (range 0-33 days) and 2 days in
      period 3 (range 0-14 days, p < 0.001). We observed a significant decrease in the
      use of deoxycholate amphotericin B (47.4%, 14.8% and 11.9%), and an increase in
      the use of echinocandins (0%, 2.8% and 49.1%; p < 0.001). The APACHE II score
      increased over time (median 16, 17.5, and 22, p < 0.001). The overall 30-day
      mortality was 58.9%, and did not change significantly over the study period.
      CONCLUSIONS: There was an improvement in patient care, with an increase in the
      proportion of patients receiving treatment and a decrease in the time to
      treatment initiation, but no improvement in the outcome, possibly because the
      proportion of sicker patients increased over time.

PMID- 30118655
TI  - Casein kinase-II inhibition promotes retinal ganglion cell survival and axonal
      regeneration.
AB  - Neuron survival is critical for the maintenance of central nervous system
      physiology upon diseases or injury. We previously demonstrated that the blockage
      of phosphatidylinositol 3-kinase/Akt and Janus kinase/STAT3 pathways promotes
      retinal ganglion cell (RGC) survival and axonal regeneration via macrophage
      activation; yet, the complexity of the inflammatory regulation for neural repair
      indicates the involvement of additional unresolved signaling pathways. Here we
      report the effects and underlying mechanism of casein kinase-II (CK2) inhibition
      on RGC survival and axonal regeneration in rats after optic nerve (ON) injury.
      Adult rats received intravitreal injection of CK2 inhibitors, TBB (4,5,6,7
      Tetrabromo-2-azabenzimidazole) and DMAT (2-Dimethylamino-4,5,6,7-tetrabromo-1H
      benzimidazole), after ON transection and peripheral nerve (PN) grafting.
      Intravitreal application of TBB and DAMT effectively suppressed the CK2
      phosphorylation activity in the retina, and enhanced RGC survival and axonal
      regeneration in vivo. Meanwhile, the numbers of infiltrating macrophages were
      increased. Removal of macrophages by clodronate liposomes significantly abolished
      the CK2 inhibition-induced RGC survival and axonal regeneration. Clodronate
      liposomes also weakened the RGC protective effects by TBB and DMAT in vitro. In
      summary, this study revealed that inhibition of CK2 enhances RGC survival and
      axonal regeneration via macrophage activation in rats. CK2 could be a therapeutic
      target for RGC protection after ON injury.

PMID- 30118656
TI  - Collagen fiber crimping following in vivo UVA-induced corneal crosslinking.
AB  - The purpose of this study was to measure collagen fiber crimping (CFC) using
      nonlinear optical imaging of second harmonic generated (SHG) signals to determine
      the effects of UVA-riboflavin induced corneal collagen crosslinking (UVA CXL) on
      collagen structure. Two groups, four rabbits each, were treated in the right eye
      with standard UVA CXL. In vivo confocal microscopy was performed at 1, 2, and 4
      weeks after treatment for the first group and up to three months for the second
      group to measure epithelial/stromal thickness and corneal haze during recovery.
      Rabbits were sacrificed at one and three months, respectively, and their corneas
      fixed under pressure. Regions of crosslinking were identified by the presence of
      collagen autofluorescence (CAF) and then collagen structure was imaged using SHG
      microscopy. The degree of CFC was determined by measuring the percentage
      difference between the length of the collagen fiber and the linear distance
      traveled. CFC was measured in the central anterior and posterior CXL region, the
      peripheral non-crosslinked region in the same cornea, and the central cornea of
      the non-crosslinked contralateral eye. No change in corneal thickness was
      detected after one month, however the stromal thickness surpassed its original
      baseline thickness at three months by 25.9 MUm. Corneal haze peaked at one month
      and then began to clear. Increased CAF was detected in all CXL corneas, localized
      to the anterior stroma and extending to 42.4 +/- 3.4% and 47.7 +/- 7.6% of the
      corneal thickness at one and three months. There was a significant (P < 0.05)
      reduction in CFC in the CAF region in all eyes averaging 1.007 +/- 0.006 and
      1.009 +/- 0.005 in one and three month samples compared to 1.017 +/- 0.04 and
      1.016 +/- 0.06 for controls. These results indicate that there is a significant
      reduction in collagen crimping following UVA CXL of approximately 1%. One
      possible explanation for this loss of crimping could be shortening of the
      collagen fibers over the CXL region.

PMID- 30118658
TI  - Liquid biopsies for management of pancreatic cancer.
AB  - Pancreatic cancer is one of the main causes of cancer-related deaths worldwide.
      It is asymptomatic at an early stage, and most diagnosis occurs when the disease
      is already at a late stage, by which time the tumor is nonresectable. In order to
      increase the overall survival of patients with pancreatic cancer, as well as to
      decrease the cancer burden, it is necessary to perform early diagnosis, prognosis
      stratifications and cancer monitoring using accurate, minimally invasive, and
      cost-effective methods. Liquid biopsies seek to detect tumor-associated
      biomarkers in a variety of extractable body fluids and can help to monitor
      treatment response and disease progression, and even predict patient outcome. In
      patients with pancreatic cancer, tumor-derived materials, primarily circulating
      tumor DNA, circulating tumor cells and exosomes, are being studied for inclusion
      in the management of the disease. This review focuses on describing the biology
      of these biomarkers, methods for their enrichment and detection, as well as their
      potential for clinical application. Moreover, we discuss the future direction of
      liquid biopsies and introduce how they can be exploited toward point of care
      personalized medicine for the management of pancreatic cancer.

PMID- 30118657
TI  - The HU177 Collagen Epitope Controls Melanoma Cell Migration and Experimental
      Metastasis by a CDK5/YAP-Dependent Mechanism.
AB  - Stromal components not only help form the structure of neoplasms such as
      melanomas, but they also functionally contribute to their malignant phenotype.
      Thus, uncovering signaling pathways that integrate the behavior of both tumor and
      stromal cells may provide unique opportunities for the development of more
      effective strategies to control tumor progression. In this regard, extracellular
      matrix-mediated signaling plays a role in coordinating the behavior of both tumor
      and stromal cells. Here, evidence is provided that targeting a cryptic region of
      the extracellular matrix protein collagen (HU177 epitope) inhibits melanoma tumor
      growth and metastasis and reduces angiogenesis and the accumulation of alpha-SMA
      expressing stromal cell in these tumors. The current study suggests that the
      ability of the HU177 epitope to control melanoma cell migration and metastasis
      depends on the transcriptional coactivator Yes-associated protein (YAP). Melanoma
      cell interactions with the HU177 epitope promoted nuclear accumulation of YAP by
      a cyclin-dependent kinase-5-associated mechanism. These findings provide new
      insights into the mechanism by which the anti-HU177 antibody inhibits metastasis,
      and uncovers an unknown signaling pathway by which the HU177 epitope selectively
      reprograms melanoma cells by regulating nuclear localization of YAP. This study
      helps to define a potential new therapeutic strategy to control melanoma tumor
      growth and metastasis that might be used alone or in combination with other
      therapeutics.

PMID- 30118660
TI  - Crystallization of Human Erythrocyte Band 3, the anion exchanger, at the
      International Space Station "KIBO".
AB  - Band 3 mediates the Cl- and HCO3- exchange across the red blood cell membrane and
      plays a pivotal role for delivering oxygen appropriately to metabolically active
      tissues. For understanding molecular mechanisms, it is essential to know the
      structure and function relationship. In terrestrial environments, however, nobody
      could make good quality crystals of Band 3 for the X-ray crystallographic study.
      In this study, we purified the transmembrane domain of Band 3 from human red
      blood cells and crystallized the purified Band 3 without the Fab fragment at the
      International Space Station "KIBO" under microgravity environments.

PMID- 30118661
TI  - Chrysin attenuates carrageenan-induced pleurisy and lung injury via activation of
      SIRT1/NRF2 pathway in rats.
AB  - Chrysin, a natural polyphenol plentifully contained in honey, propolis,
      vegetables and fruits, it has been reported to exert a variety of pharmacological
      activities. In the present study, we mainly investigated the protective effects
      and underlying molecular mechanisms of chrysin on carrageenan-induced lung injury
      in rats. The results showed that chrysin inhibited the neutrophils infiltration,
      attenuated histological injury of lung tissues, decreased PMNs markers level and
      oxidative stress markers levels of lungs in rats. Further studies showed chrysin
      can inhibit the NF-kB activation in neutrophils cells, activate SIRT1/NRF2
      pathway and reduce the expression of adhesion molecule in lung tissues. Taken
      together, these results suggested that chrysin can attenuate carrageenan-induced
      lung injury via inhibition of neutrophils activation and oxidative stress
      response, and that this attenuation is, at least partially, related to up
      regulation of SIRT1/NRF2 signaling pathway. This study also validates SIRT1/NRF2
      is an effective pharmacological target to protect against carrageenan-induced
      lung injury.

PMID- 30118659
TI  - Functional characterization of alternatively spliced GSN in head and neck
      squamous cell carcinoma.
AB  - We have recently performed the characterization of alternative splicing events
      (ASEs) in head and neck squamous cell carcinoma, which allows dysregulation of
      protein expression common for cancer cells. Such analysis demonstrated a high ASE
      prevalence among tumor samples, including tumor-specific alternative splicing in
      the GSN gene.In vitro studies confirmed that overall expression of either ASE-GSN
      or wild-type GSN (WT-GSN) isoform inversely correlated with cell proliferation,
      whereas the high ratio of ASE-GSN to WT-GSN correlated with increased cellular
      invasion. Additionally, a change in expression of either isoform caused
      compensatory changes in expression of the other isoform. Our results suggest that
      the overall expression and the balance between GSN isoforms are mediating factors
      in proliferation, while increased overall expression of ASE-GSN is specific to
      cancer tissues. As a result, we propose ASE-GSN can serve not only as a biomarker
      of disease and disease progression, but also as a neoantigen for head and neck
      squamous cell carcinoma treatment, for which only a limited number of disease
      specific targeted therapies currently exist.

PMID- 30118663
TI  - Cannabinoid signalling in the immature brain: Encephalopathies and
      neurodevelopmental disorders.
AB  - The endocannabinoid system exerts a crucial neuromodulatory role in many brain
      areas that is essential for proper regulation of neuronal activity. The role of
      cannabinoid signalling controlling neuronal activity in the adult brain is also
      evident when considering its contribution to adult brain insults or
      neurodegenerative diseases. In the context of brain genetic or acquired
      encephalopathies administration of cannabinoid-based molecules has demonstrated
      to exert symptomatic relief and hence, they are proposed as new potential
      therapeutic compounds. This review article summarizes the main evidences
      indicating the beneficial action of cannabinoid-derived molecules in preclinical
      models of neonatal hypoxia/ischemic damage. In a second part, we discuss the
      available evidences of therapeutic actions of cannabidiol in children with
      refractory epilepsy syndromes. Finally, we discuss the current view of
      cannabinoid signalling mechanisms active in the immature brain that affect in
      neural cell fate and can contribute to long-term neural cell plasticity.

PMID- 30118662
TI  - The ERM family member Merlin is required for endometrial gland morphogenesis.
AB  - Disruption of endometrial gland formation or function can cause female
      infertility. Formation of endometrial glands via tubulogenesis of luminal
      epithelial cells requires the establishment and maintenance of cell polarity and
      cell adhesion. The FERM domain-containing protein Merlin coordinates epithelial
      cell polarity and cell adhesion and is critical for epithelial tissue function in
      the skin and kidney. We now demonstrate a requirement for Merlin in endometrial
      gland development. Conditional deletion of Merlin in the endometrium results in
      female infertility caused by the absence of gland formation. Interestingly, we
      observed glandular epithelial markers within discrete groups of cells in the
      Merlin-deficient luminal epithelium. Wnt signaling, a pathway necessary for
      endometrial gland development is maintained in Merlin-deficient endometrium,
      suggesting the glandular fate program is active. Instead, we observe increased
      levels of apical actin and markers indicative of high membrane tension on the
      basal surface of the Merlin-deficient luminal epithelium. These findings suggest
      that the structural integrity of the luminal epithelium during gland formation is
      required for appropriate endometrial tubulogenesis and tissue function. Moreover,
      our work implicates Merlin-dependent regulation of mechanical tension in the
      proper formation of endometrial gland architecture and function.

PMID- 30118664
TI  - Developing a Barriers Scale in the Context of Travel: TRIP.
AB  - OBJECTIVE: To develop an environmental-barriers scale, Travel Restrictions
      Influencing Participation (TRIP), in the context of travel for people living with
      spinal cord injury (SCI). DESIGN: A mixed-method approach where, in the
      qualitative phase, items were developed and written based on results of
      interviewers with different stakeholder groups and, in the quantitative phase,
      survey data were collected to examine the psychometric properties of the scale.
      SETTING: Home, work, and community settings. PARTICIPANTS: People living with
      SCI, caregivers/family members, therapists, and travel professionals (N=333).
      INTERVENTIONS: None. MAIN OUTCOME MEASURES: A 19-item TRIP scale that measures
      the travel barriers encountered by people with SCI. RESULTS: Results from 83 semi
      structured in-depth interviews with 4 stakeholder groups guided the writing of
      items in the TRIP scale. Seven cognitive interviews and an expert panel conducted
      reviews for content validity of the scale, and 19 items were included in the
      quantitative assessment of the scale. A total of 250 patients enrolled in the
      Rocky Mountain Regional Spinal Injury System was systematically selected to
      report their experience with each travel barrier. Item-response theory-based
      Rasch analysis revealed that TRIP has acceptable psychometric properties.
      CONCLUSIONS: The 19-item TRIP scale demonstrates promising psychometric
      properties for the scale to be used in clinical settings to quickly identify
      environmental barriers individuals with SCI encounter when traveling. It has the
      potential to assist with developing interventions that will improve the travel
      experience of individuals with SCI or to assist with strategies to overcome
      travel barriers.

PMID- 30118665
TI  - Apnea-Hypopnea Index in Healthy Class III Patients Treated With Intraoral
      Vertical Ramus Osteotomy: A Prospective Cohort Study.
AB  - PURPOSE: The study purpose was to assess whether mandibular setback surgery by
      intraoral vertical ramus osteotomy (IVRO) induces obstructive apnea and hypopnea
      in healthy Class III patients without a history of respiratory dysfunction. We
      hypothesized that the apnea-hypopnea index (AHI) would not exceed 5 events per
      hour after surgery. PATIENTS AND METHODS: A prospective cohort study was
      conducted. The sample was composed of healthy Class III patients without a
      history of obstructive sleep apnea treated with isolated mandibular setback
      surgery by the IVRO procedure at a university hospital. In-home respiratory sleep
      recordings (Nox T3; Nox Medical, Reykjavik, Iceland) and self-administered
      questionnaires were obtained before and at least 3 months after surgery. The AHI
      was the primary outcome variable. Other study variables were as follows:
      peripheral capillary oxygen saturation, oxygen desaturation index, snore index,
      body mass index, Epworth Sleepiness Scale, and Oral Impact on Daily Performance
      index. Descriptive and bivariate statistics were computed, and the significance
      level was set at .05. RESULTS: The sample was composed of 8 patients. The mean
      age at surgery was 23.2 years (range, 18.2 to 33.4 years). The mean amount of
      surgical setback was 4.3 mm (range, 2.5 to 7.4 mm). The mean body mass index was
      24.2 kg/m2 (standard error [SE], 1.3 kg/m2) and 23.9 kg/m2 (SE, 1.4 kg/m2) at the
      presurgical and postsurgical sleep recordings, respectively. The mean AHI was 1.3
      events per hour (SE, 0.3; range, 0.1 to 2.5) before surgery and 1.8 events per
      hour (SE, 0.4; range, 0.3 to 3.3) after surgery. No statistically significant
      changes in AHI (P = .412), peripheral capillary oxygen saturation (P = .443),
      oxygen desaturation index (P = .194), snore index (P = .363), or Epworth
      Sleepiness Scale (P = .812) were observed. The patients' self-reported oral
      health-related quality of life was statistically significantly improved after
      surgery (P = .034). CONCLUSIONS: Mandibular setback surgery with the IVRO
      procedure in the range of 2.5 to 7.4 mm did not induce obstructive sleep apnea,
      measured as an AHI above 5 events per hour, in the 8 healthy, young adult Class
      III patients presented in this study. More studies including larger patient
      samples are needed.

PMID- 30118666
TI  - Modified Temporomandibular Joint Disc Repositioning With Miniscrew Anchor: Part
      II-Stability Evaluation by Magnetic Resonance Imaging.
AB  - PURPOSE: The purpose of this study was to evaluate the stability of disc position
      and condylar status by magnetic resonance imaging (MRI) after temporomandibular
      joint (TMJ) disc repositioning surgery with a miniscrew anchor technique.
      MATERIALS AND METHODS: Patients diagnosed with anterior disc displacement (ADD)
      and operated on for disc repositioning from 2010 through 2016 were included in
      the study. MRI scans within 1 week after operation (T1) and during at least 1
      year follow-up were used to evaluate changes in disc position and condylar bone.
      During follow-up, ADD without reduction was considered relapse and the bone
      status was classified as regeneration or degeneration. RESULTS: One hundred seven
      patients with 149 joints were included in the study. Postoperative MRI scans (T1)
      showed that all discs were repositioned. During an average 23.40-month follow-up
      (range, 12 to 84 months), 95.3% of discs (142 of 149) were still in position,
      whereas 4.7% of discs (7 of 149) had relapsed anteriorly. New condylar bone
      formation was observed in 74.50% of joints (111 of 149), no bone change was
      observed in 23.49% of joints (35 of 149), and bone resorption was observed in
      2.01% of joints (3 of 149). CONCLUSIONS: TMJ disc repositioning by a miniscrew
      anchor provides stability for treatment of ADD. Disc repositioning also can
      stimulate condylar bone regeneration.

PMID- 30118667
TI  - Are Emergency Medicine Physicians Able to Determine the Need for Computed
      Tomography and Specialist Consultation in Odontogenic Maxillofacial Infections?
AB  - PURPOSE: Pain and swelling from a necrotic tooth is a common complaint in
      emergency departments. These patients impose substantial burdens on hospital
      budgets and provider time. The initial triage of odontogenic infections can be
      difficult without advanced knowledge and training in head and neck anatomy and
      odontogenic disease pathogenesis. The purpose of this study was to determine the
      frequency with which emergency medicine physicians correctly determine the need
      for computed tomography (CT) and specialist consultation in patients with
      odontogenic infections. MATERIALS AND METHODS: A retrospective case series was
      designed. Patients older than 18 years with an odontogenic infection presenting
      to the emergency department from August 1, 2012 to April 30, 2015 were eligible
      for inclusion in the study. Demographic, clinical, laboratory, and treatment data
      were recorded, with special attention paid to the hospital service consulted and
      imaging ordered. The location of the abscess and the clinical presentation of the
      patient were used to determine the necessity for the imaging and consultation.
      Descriptive statistics were used to analyze the data. RESULTS: Seventy-two
      patients met the inclusion criteria (52.9% women; mean age, 40.0 yr). The
      decision to order CT was made by emergency medicine physicians for 61.7% of
      patients with infections that did not require CT. Likewise, oral and
      maxillofacial surgery was consulted for 77.8% of patients with infections that
      did not require a specialist consultation. CONCLUSION: In this study, emergency
      medicine physicians misinterpreted the clinical needs of a large percentage of
      patients with odontogenic infections. Better education, interdepartmental
      collaboration, and conducting and disseminating peer-reviewed research are
      several ways to increase efficiency of care in patients with odontogenic
      infections.

PMID- 30118668
TI  - Severe Anxiety Among Female Oral-Maxillofacial Surgery Residents: Can Gender
      Discrimination Be a Cause?

PMID- 30118669
TI  - In Reply.

PMID- 30118670
TI  - Fighting Kinase Drug Resistance with Caspase Activators.
AB  - Kinase inhibitors are effective cancer therapies. Unfortunately, drug resistance
      emerges in response to kinase inhibition leading to loss of drug efficacy. In
      this issue of Cell Chemical Biology, Peh et al. (2018) demonstrate that caspase
      activators effectively delay onset of resistance to kinase inhibitors and are
      excellent co-therapeutics for a number of tumor types.

PMID- 30118671
TI  - Dysregulating ClpP: From Antibiotics to Anticancer?
AB  - In this issue of Cell Chemical Biology, Wong et al. (2018) identify several
      dysregulators of a key mitochondrial protease: casein lytic protease P (ClpP).
      These dysregulators were found to trigger programmed cell death and may offer
      fresh avenues for the development of novel cancer therapeutics.

PMID- 30118672
TI  - Serum leucine-rich alpha2-glycoprotein is elevated in patients with systemic
      lupus erythematosus and correlates with disease activity.
AB  - BACKGROUND: We evaluated whether serum leucine-rich alpha2-glycoprotein (LRG) is
      associated with disease activity in patients with systemic lupus erythematosus
      (SLE). METHODS: We measured serum LRG in 194 SLE patients. SLE disease activity
      index-2000 (SLEDAI-2 K) was used to assess SLE activity, and patients with SLEDAI
      2 K >=5 were defined as having active SLE. Correlation between serum LRG, SLEDAI
      2 K, and laboratory variables was estimated by Pearson's correlation analysis.
      The optimal serum LRG cut-off value for predicting active SLE was calculated
      using receiver operator characteristic (ROC) curve, and multivariable logistic
      regression was used to determine the odds ratio (OR) of laboratory variables.
      RESULTS: In total, 74 (38.1%) and 120 (61.9%) patients were classified as active
      and inactive SLE, respectively. Serum LRG was higher in patients with active SLE
      than in inactive SLE and healthy controls (26.6 vs. 14.4 vs. 1.2 ng/ml, p <
      .001). Serum LRG significantly correlated with SLEDAI-2 K (r = 0.340, p < .001)
      and laboratory variables. ROC analysis revealed that optimal serum LRG cut-off
      value for active SLE was >45.7 ng/ml. In multivariable logistic regression
      analysis, serum LRG >45.7 ng/ml (OR 4.089, 95% confidence interval 1.351, 12.376,
      p = .013) was an independent predictor of active SLE. CONCLUSIONS: Serum LRG
      might be a biomarker for estimating SLE disease activity.

PMID- 30118673
TI  - Analytical performance evaluation of the new GEM(r) PremierTM 5000 analyzer in
      comparison to the GEM(r) PremierTM 4000 and the RapidPoint(r) 405 systems.
AB  - AIM OF THE STUDY: Blood gas analysis (BGA) is essential for the diagnosis and
      management of acid-base imbalances. We evaluated and compared the analytical
      characteristics of the new GEM(r) PremierTM 5000 (GP5000) (Instrumentation
      Laboratory, Bedford, MA, United States) BGA point-of-care (POC) device with those
      of the GEM(r) PremierTM 4000 (GP4000) (Instrumentation Laboratory, Bedford, MA,
      United States) and RapidPoint(r) 405 (RP405) (Siemens Healthcare, Milan, Italy)
      POC analyzers. The effect of sample mixing on patient results was also studied.
      MATERIAL AND METHODS: Quantitative measurement of pH, pCO2, pO2, Na+, K+, Cl-,
      iCa2+, glucose, lactate, tHb, COHb, MetHb, O2Hb, HHb and Hct were carried out.
      The imprecision study (IS) and method comparison study (MS) were performed
      according to CLSI EP guidelines, using respectively internal as well as external
      quality controls (IS) and whole blood samples collected from the routine analysis
      (MS). RESULTS: GP5000 demonstrated satisfactory characteristics in the IS showing
      comparable (GM4000) or even better (RP405) imprecision results than the routine
      POC devices. Good performance was observed in the MS both using GP4000 and RP405
      as reference instruments. Pre-analytical sample management can heavily affect the
      accuracy of BGA results. In the specimen mixing evaluation, a significant
      improvement in results accuracy was observed when mixing procedures were more
      meticulous. CONCLUSIONS: Considering the overall analytical performance observed,
      the ease of use of the system, the rapid time-to-results and the innovative
      Intelligent Quality Management technology (iQM2(r)), GP5000 seems suitable to be
      used in clinical care for safe patient management. Additionally, effective sample
      mixing upon draw and before analysis is strongly advisable in order to ensure the
      most clinically reliable BGA results.

PMID- 30118674
TI  - Beta-lactam carryover in arterial and central venous catheters is negligible.
AB  - BACKGROUND: Therapeutic drug monitoring is used for aminoglycosides and
      vancomycin, and has been proposed for beta-lactam antibiotics. Clinical blood
      samples in the ICU are often obtained via an existing vascular catheter rather
      than fresh needle phlebotomy. If antibiotics had previously been infused through
      a vascular catheter then used for blood sampling, carryover of antibiotic from
      the infusion to the sample might result in misleading assessments of target
      attainment. To address this concern we conducted a series of in vitro
      measurements of carryover for three commonly used antibiotics. METHODS: We
      infused piperacillin-tazobactam, meropenem, and cefepime at pharmacologic
      concentrations through commonly used vascular catheters at our hospital and
      flushed the catheters. We then aspirated warmed citrated bovine blood through
      each catheter and measured antibiotic concentrations in each aspirate. RESULTS:
      Carryover was below the limits of detection for piperacillin-tazobactam,
      meropenem, and vancomycin. Cefepime carryover, in contrast, was not negligible
      and needs to be investigated more fully. CONCLUSION: Carryover from prior
      infusions does not appear to jeopardize measurements of piperacillin-tazobactam,
      meropenem, or vancomycin in commonly used vascular catheters at our institution.
      Caution in interpreting samples obtained for cefepime measurements appears
      advised until more data is available.

PMID- 30118675
TI  - ERADicate Tumor Progression with Metformin.
AB  - Endoplasmic reticulum-associated degradation (ERAD) plays a crucial role in
      turnover of defective secretory proteins to maintain protein homeostasis. Cha et
      al. (2018) revealed that the anti-diabetic drug metformin induces ERAD of
      programmed death ligand (PD-L1), which attenuates tumor growth.

PMID- 30118676
TI  - Bacterial Protein Reshapes Host Defense toward Antiviral Responses.
AB  - In this issue of Molecular Cell, Penn et al. (2018) report the protein
      interactome between Mycobacterium tuberculosis (Mtb) secreted effectors and
      macrophage cytosolic proteins. This Resource reveals that the interaction of Mtb
      effector LpqN with host CBL counteracts antibacterial defense but causes a
      reciprocal enhancement of antiviral defense.

PMID- 30118677
TI  - Self-Digestion for Lifespan Extension: Enhanced Autophagy Delays Aging.
AB  - By systemically boosting autophagy with a knockin mutation that prevents binding
      of beclin 1 to BCL2, Fernandez et al. (2018) demonstrate that enhanced autophagy
      prolongs lifespan in mammals.

PMID- 30118678
TI  - Dismissal of RNA Polymerase II Underlies a Large Ligand-Induced Enhancer
      Decommissioning Program.
AB  - Nuclear receptors induce both transcriptional activation and repression programs
      responsible for development, homeostasis, and disease. Here, we report a
      previously overlooked enhancer decommissioning strategy underlying a large
      estrogen receptor alpha (ERalpha)-dependent transcriptional repression program.
      The unexpected signature for this E2-induced program resides in indirect
      recruitment of ERalpha to a large cohort of pioneer factor basally active FOXA1
      bound enhancers that lack cognate ERalpha DNA-binding elements. Surprisingly,
      these basally active estrogen-repressed (BAER) enhancers are decommissioned by
      ERalpha-dependent recruitment of the histone demethylase KDM2A, functioning
      independently of its demethylase activity. Rather, KDM2A tethers the E3 ubiquitin
      protein ligase NEDD4 to ubiquitylate/dismiss Pol II to abrogate eRNA
      transcription, with consequent target gene downregulation. Thus, our data reveal
      that Pol II ubiquitylation/dismissal may serve as a potentially broad strategy
      utilized by indirectly bound nuclear receptors to abrogate large programs of
      pioneer factor-mediated, eRNA-producing enhancers.

PMID- 30118679
TI  - ACP Acylation Is an Acetyl-CoA-Dependent Modification Required for Electron
      Transport Chain Assembly.
AB  - The electron transport chain (ETC) is an important participant in cellular energy
      conversion, but its biogenesis presents the cell with numerous challenges. To
      address these complexities, the cell utilizes ETC assembly factors, which include
      the LYR protein family. Each member of this family interacts with the
      mitochondrial acyl carrier protein (ACP), the scaffold protein upon which the
      mitochondrial fatty acid synthesis (mtFAS) pathway builds fatty acyl chains from
      acetyl-CoA. We demonstrate that the acylated form of ACP is an acetyl-CoA
      dependent allosteric activator of the LYR protein family used to stimulate ETC
      biogenesis. By tuning ETC assembly to the abundance of acetyl-CoA, which is the
      major fuel of the TCA cycle and ETC, this system could provide an elegant
      mechanism for coordinating the assembly of ETC complexes with one another and
      with substrate availability.

PMID- 30118680
TI  - Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated
      Degradation of PD-L1.
AB  - Metformin has been reported to possess antitumor activity and maintain high
      cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and
      detailed mechanisms of metformin's role in cancer immunity are not fully
      understood. Here, we show that metformin increases CTL activity by reducing the
      stability and membrane localization of programmed death ligand-1 (PD-L1).
      Furthermore, we discover that AMP-activated protein kinase (AMPK) activated by
      metformin directly phosphorylates S195 of PD-L1. S195 phosphorylation induces
      abnormal PD-L1 glycosylation, resulting in its ER accumulation and ER-associated
      protein degradation (ERAD). Consistently, tumor tissues from metformin-treated
      breast cancer patients exhibit reduced PD-L1 levels with AMPK activation.
      Blocking the inhibitory signal of PD-L1 by metformin enhances CTL activity
      against cancer cells. Our findings identify a new regulatory mechanism of PD-L1
      expression through the ERAD pathway and suggest that the metformin-CTLA4 blockade
      combination has the potential to increase the efficacy of immunotherapy.

PMID- 30118681
TI  - Coordination between Two Branches of the Unfolded Protein Response Determines
      Apoptotic Cell Fate.
AB  - The kinases PERK and IRE1 alleviate endoplasmic reticulum (ER) stress by
      orchestrating the unfolded protein response (UPR). If stress mitigation fails,
      PERK promotes cell death by activating pro-apoptotic genes, including death
      receptor 5 (DR5). Conversely, IRE1-which harbors both kinase and endoribonuclease
      (RNase) modules-blocks apoptosis through regulated IRE1-dependent decay (RIDD) of
      DR5 mRNA. Under irresolvable ER stress, PERK activity persists, whereas IRE1
      paradoxically attenuates, by mechanisms that remain obscure. Here, we report that
      PERK governs IRE1's attenuation through a phosphatase known as RPAP2 (RNA
      polymerase II-associated protein 2). RPAP2 reverses IRE1 phosphorylation,
      oligomerization, and RNase activation. This inhibits IRE1-mediated adaptive
      events, including activation of the cytoprotective transcription factor XBP1s,
      and ER-associated degradation of unfolded proteins. Furthermore, RIDD termination
      by RPAP2 unleashes DR5-mediated caspase activation and drives cell death. Thus,
      PERK attenuates IRE1 via RPAP2 to abort failed ER-stress adaptation and trigger
      apoptosis.

PMID- 30118682
TI  - An Mtb-Human Protein-Protein Interaction Map Identifies a Switch between Host
      Antiviral and Antibacterial Responses.
AB  - Although macrophages are armed with potent antibacterial functions, Mycobacterium
      tuberculosis (Mtb) replicates inside these innate immune cells. Determinants of
      macrophage intrinsic bacterial control, and the Mtb strategies to overcome them,
      are poorly understood. To further study these processes, we used an affinity tag
      purification mass spectrometry (AP-MS) approach to identify 187 Mtb-human protein
      protein interactions (PPIs) involving 34 secreted Mtb proteins. This interaction
      map revealed two factors involved in Mtb pathogenesis-the secreted Mtb protein,
      LpqN, and its binding partner, the human ubiquitin ligase CBL. We discovered that
      an lpqN Mtb mutant is attenuated in macrophages, but growth is restored when CBL
      is removed. Conversely, Cbl-/- macrophages are resistant to viral infection,
      indicating that CBL regulates cell-intrinsic polarization between antibacterial
      and antiviral immunity. Collectively, these findings illustrate the utility of
      this Mtb-human PPI map for developing a deeper understanding of the intricate
      interactions between Mtb and its host.

PMID- 30118683
TI  - Acceptability of the distribution of DMPA-SC by community health workers among
      acceptors in the rural province of Lualaba in the Democratic Republic of the
      Congo: a pilot study.
AB  - OBJECTIVES: The objective of this research is to assess the acceptability of the
      provision of subcutaneously administered depo medroxyprogesterone acetate (DMPA
      SC) by nonclinically trained community health workers (CHWs) among acceptors in
      the rural province of Lualaba in the Democratic Republic of the Congo (DRC).
      STUDY DESIGN: In 2017, 34 CHWs received training in provision of DMPA-SC. Among
      other methods, DMPA-SC by CHWs was offered during household visits and at
      community outreach events. The initial survey included questions on acceptors'
      demographic characteristics, contraceptive use history and experience with
      provision of DMPA-SC by a CHW. The follow-up included questions about side
      effects experienced and continuation of DMPA-SC by a CHW. RESULTS: Seventy-four
      percent of initial acceptors of DMPA-SC (N=252) were first-time contraception
      users. Almost all (96.0%) felt very comfortable with a CHW performing the
      injection rather than a physician or nurse, and 97.6% perceived that the CHW was
      very comfortable performing the injection. A total of 239 women were interviewed
      at follow-up. Most expressed satisfaction with the method despite some side
      effects experienced. Almost all acceptors (97.9%) were satisfied with the
      information provided by CHWs, and 93.8% were satisfied with the overall service.
      Most (96.4%) would choose to continue receiving DMPA-SC by a CHW rather than in a
      health clinic, and 95.2% would recommend DMPA-SC by a CHW to a friend.
      CONCLUSIONS: Overall, administration of DMPA-SC by CHWs is acceptable to users in
      Lualaba. DMPA-SC can be safely provided within the community after proper
      training. IMPLICATIONS: This study validates the use of CHWs (without clinical
      training) to provide DMPA-SC in a rural sub-Saharan African setting. It also
      represents an important step in obtaining official MOH authorization for the
      scale-up of this mechanism of distribution to other underserved regions in the
      DRC.

PMID- 30118684
TI  - Combined oral contraceptive interference with the ability of ulipristal acetate
      to delay ovulation: A prospective cohort study.
AB  - OBJECTIVE: To determine if a combined oral contraceptive (COC) initiated shortly
      after ulipristal acetate (UPA) administration interferes with its mechanism of
      action. STUDY DESIGN: Healthy, reproductive-age women of normal BMI with proven
      ovulation (serum progesterone >3 ng/ml) were enrolled for three cycles (Cycle 1,
      UPA only; Cycle 2 washout; Cycle 3 UPA plus COC). During Cycles 1 and 3, subjects
      were monitored with transvaginal ultrasound and blood sampling for progesterone
      and LH every other day until a dominant follicle measuring >15 mm was visualized.
      In both treatment cycles, subjects received UPA (30mg) and were followed daily
      with similar monitoring for up to 7 days. In Cycle 3 only, subjects initiated a
      daily COC (0.15 mg levonorgestrel/30 MUg ethinyl estradiol) 2 days after UPA. The
      study had 80% power to detect a 15% difference in the proportion of cycles with
      at least a 5-day delay in follicle rupture. We assessed follicle rupture as >50%
      decrease in mean size and adjudicated unclear outcomes with serum hormones.
      RESULTS: A total of 36 women enrolled and 33 completed all study procedures [age
      28.4 years (SD 3.9); BMI 23.4 (SD 2.4)]. Compared to Cycle 1, more subjects
      demonstrated evidence of follicle rupture in <5 days in Cycle 3 [1/33 (3%) vs.
      9/33 (27%), p = .008]. We also included data from 2 subjects who experienced
      rupture prior to COC dosing in the analysis. CONCLUSION: UPA's effectiveness is
      significantly reduced by administering COCs 2 days later. IMPLICATIONS: This
      study demonstrates that UPA's efficacy as an emergency contraceptive is reduced
      with early exposure to COCs.

PMID- 30118686
TI  - Evaluation of Retromode Imaging for Use in Hydroxychloroquine Retinopathy.
AB  - PURPOSE: To report on the application of retromode imaging using infrared lasers
      to eyes with hydroxychloroquine (HCQ) retinopathy, and to compare retromode
      images with those acquired via conventional objective screening imaging
      modalities-optical coherence tomography (OCT) and fundus autofluorescence (FAF).
      DESIGN: Diagnostic validity assessment. METHODS: Setting: Institutional. PATIENT
      POPULATION: Sixty-two eyes of 31 patients with systemic lupus erythematosus or
      rheumatoid arthritis who were treated with HCQ and developed HCQ retinopathy
      (patient group), 270 eyes of 135 patients with the same diseases who were treated
      with HCQ but exhibit no retinopathy (HCQ-taking control group), and 162 eyes of
      81 normal controls (normal control group). OBSERVATION PROCEDURES: Diagnosis of
      HCQ retinopathy was performed with screening tests recommended by the American
      Academy of Ophthalmology, including OCT, FAF, and visual field examination.
      Retromode imaging, using confocal scanning laser ophthalmoscopy, was performed
      for the patient group and both control groups. The findings on retromode imaging
      were correlated with outer retinal changes on OCT B-scan images, then compared
      with the FAF findings. The sensitivity and specificity of retromode imaging were
      calculated. MAIN OUTCOME MEASURES: Findings of retromode imaging and
      sensitivity/specificity of the imaging. RESULTS: All patients with HCQ
      retinopathy showed a parafoveal or pericentral ring-shaped or round area of
      decreased reflectance with prominent deep choroidal vessels, resulting in 100%
      sensitivity for the detection of retinopathy. Specificity of the imaging was
      73.0% and 76.4% in the HCQ-taking control group and both control groups,
      respectively. Compared to FAF, retromode imaging enabled the detection of
      photoreceptor defects with greater sensitivity, particularly in eyes with early
      retinopathy. However, FAF provided additional information on the status of the
      retinal pigment epithelium, which could not be discriminated from photoreceptor
      defects in retromode imaging. CONCLUSIONS: Retromode imaging may be useful for
      detecting HCQ retinopathy. However, its excellent sensitivity but limited
      specificity is suggestive of a supplementary role in screening HCQ retinopathy,
      particularly for early detection.

PMID- 30118685
TI  - Presbyopia and Ocular Conditions Causing Near Vision Impairment in Older Adults
      From the Brazilian Amazon Region.
AB  - PURPOSE: To investigate the prevalence and causes of near vision impairment (NVI)
      in a population of older adults from the Brazilian Amazon Region. DESIGN:
      Population-based cross-sectional study. METHODS: Cluster sampling was used in
      randomly selecting subjects 45 years of age and older from urban and rural areas
      of Parintins city, Brazil. Participants underwent ophthalmic examination,
      including uncorrected (UCNVA), presenting (PNVA), and best-corrected near visual
      acuity (BCNVA) from each eye; biomicroscopy; funduscopy; and subjective
      refraction, including testing with additional lenses for near vision optical
      correction. A principal cause for NVI was assigned by the ophthalmologist and
      presbyopia was defined as UCNVA <= 20/40 changing to > 20/40 with BCNVA. Free-of
      charge glasses were provided for those in need. RESULTS: A total of 2384 subjects
      were enumerated and 2025 had reliable NVA measurements from both eyes. The
      prevalence of NVI in the better-seeing eye was 96.5% with UCNVA, decreasing to
      81.1% with PNVA and to 20.5% with BCNVA. Presbyopia was the principal cause of
      NVI in 71.8%, followed by cataract (16.5%) and pterygium (2.5%), and was
      associated with younger age and high schooling. Glasses for near vision were
      prescribed and provided to 1414 (69.8%) participants. CONCLUSIONS: A high
      prevalence of NVI was detected even in those wearing glasses for near.
      Prescription and provision of low-cost reading glasses should be considered by
      Brazilian health authorities to address this easily and promptly correctable form
      of vision impairment.

PMID- 30118687
TI  - Iris Microhemangiomatosis: Clinical, Fluorescein Angiography, and Optical
      Coherence Tomography Angiography Features in 14 Consecutive Patients.
AB  - PURPOSE: To describe the clinical and imaging findings and treatment options in a
      series of patients with iris microhemangiomatosis. DESIGN: Retrospective
      observational case series. METHODS: Setting: Single institution. STUDY
      POPULATION: Twenty-two eyes of 14 consecutive patients with iris
      microhemangiomatosis were reviewed. OBSERVATION PROCEDURES: Clinical examination
      and slit-lamp photography were performed on every patient. Anterior segment
      optical coherence tomography (AS-OCT), anterior segment optical coherence
      tomography angiography (AS-OCTA), anterior segment intravenous fluorescein
      angiography (AS-IVFA), and ultrasound biomicroscopy were performed when possible.
      MAIN OUTCOME MEASURES: Clinical and imaging features and treatment strategies.
      RESULTS: Twenty-two eyes of 14 patients with iris microhemangiomatosis were
      included in this series. Mean patient age was 70 years (range, 58-82 years), and
      all patients were white. The iris hemangiomatosis appeared as subtle, multifocal,
      ectatic vascular channels arranged circumferentially at the pupillary margin.
      Iris color was blue (n = 19 eyes) or green (n = 3 eyes), and the features were
      unilateral (n = 6 patients) or bilateral (n = 8 patients). Additional features
      included reduced visual acuity (n = 13 eyes), hyphema (n = 12 eyes), and glaucoma
      (n = 7 eyes). There was no history of ocular trauma or systemic vasculopathic
      conditions. AS-OCT documented the fine tuft at the pupillary margin, AS-OCTA
      showed vascular flow, and AS-IVFA demonstrated pupillary margin vascular lesions
      with mild staining. Observation was advised in 20 cases (91%), and argon laser
      photocoagulation was required for repetitive hyphema in 2 cases (9%). CONCLUSION:
      Iris microhemangiomatosis is a rare ocular condition, often manifesting with
      spontaneous unilateral hyphema and/or secondary glaucoma. AS-IVFA confirms the
      diagnosis, and intervention with laser photocoagulation is necessary in only 9%
      of eyes.

PMID- 30118688
TI  - Topographic Analysis of the Choriocapillaris in Intermediate Age-related Macular
      Degeneration.
AB  - PURPOSE: To quantitate regional differences in the choriocapillaris (CC) of
      patients with intermediate age-related macular degeneration (iAMD), using swept
      source optical coherence tomography angiography (SS-OCTA) imaging. DESIGN: Cross
      sectional study. METHODS: Subjects were imaged with the SS-OCTA system (PLEX
      Elite 9000, Carl Zeiss Meditec Inc, Dublin, California, USA). The CC en face
      images were first compensated for the signal attenuation caused by drusen by
      using the structural information from the same slab. Subsequently, for each eye,
      2 compensated CC en face images generated from 2 different OCTA volume scan sets
      were registered and averaged. The averaged CC images were then exported to ImageJ
      and binarized for subsequent quantitative analysis. In addition to the analysis
      of the whole averaged CC en face image in iAMD eyes, quantitative analysis was
      also performed in 3 different regions: (1) drusen region, (2) 150-MUm-wide ring
      around the drusen border, and (3) drusen-free region. RESULTS: Thirty eyes (30
      patients) with iAMD and 30 healthy eyes from 30 controls were enrolled. Compared
      with controls, iAMD eyes displayed a lower number of signal voids (median and
      interquartile range [IQR]: 2561 and 2343-2746 vs 2734 and 2558-2834; P = .013), a
      greater signal void average size (median, IQR: 581.9 MUm2, 466.1-726.9 MUm2 vs
      503.8 MUm2, 429.1-576.8 MUm2; P = .027), and a greater total signal void area
      (median, IQR: 26.0%, 22.1%-29.6% vs 23.8%, 21.2%-26.4%; P = .038). In multiple
      regression analysis, the presence of iAMD was not significantly associated with
      any of the CC variables. By contrast, the drusen region area was significantly
      associated with CC alterations. In the evaluation of the iAMD group, both the
      area underneath drusen and the 150-MUm-wide ring region around drusen were
      characterized by an increased total signal void area (P = .005 and P = .045,
      respectively) vs the drusen-free region. CONCLUSIONS: Intermediate AMD eyes
      demonstrated increased CC flow impairment, which co-localizes to the area of CC
      beneath and immediately surrounding drusen.

PMID- 30118689
TI  - Comparing the Hadlock fetal growth standard to the Eunice Kennedy Shriver
      National Institute of Child Health and Human Development racial/ethnic standard
      for the prediction of neonatal morbidity and small for gestational age.
AB  - BACKGROUND: The fetal growth standard in widest use was published by Hadlock >25
      years ago and was derived from a small, homogeneous cohort. In 2015, The Eunice
      Kennedy Shriver National Institute of Child Health and Human Development Fetal
      Growth Study published updated standards that are specific to race/ethnicity.
      These do not allow for precise estimated fetal weight percentile calculation,
      however, and their effectiveness to predict neonatal morbidity and small for
      gestational age has not yet been compared to the long-standing Hadlock standard.
      OBJECTIVE: We compared the ability of the Hadlock standard to predict neonatal
      morbidity and small for gestational age at birth with that of The Eunice Kennedy
      Shriver National Institute of Child Health and Human Development race-/ethnicity
      specific standard. Our secondary objective was to compare their performance among
      our Native American population, which is not accounted for in the Eunice Kennedy
      Shriver National Institute of Child Health and Human Development standard. STUDY
      DESIGN: For this retrospective study of diagnostic accuracy, we reviewed
      deliveries at the University of New Mexico Hospital from Jan. 1, 2013, through
      March 31, 2017. We included mothers with singleton, well-dated pregnancies and
      nonanomalous fetuses with an estimated fetal weight within 30 days of delivery.
      Cubic spline interpolation was performed on the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development estimated fetal weight-percentile
      tables to calculate percentiles specific to the gestational day. Estimated fetal
      weight percentiles were then calculated using both the Hadlock and Eunice Kennedy
      Shriver National Institute of Child Health and Human Development race-/ethnicity
      specific standards according to maternal self-identified race/ethnicity. We
      calculated the receiver operator area under the curve of each method to predict
      composite and severe composite neonatal morbidity and small for gestational age
      at birth (birthweight <10th percentile). As an additional measure of method
      accuracy, we calculated the mean ultrasound-birthweight percentile discrepancy.
      For Native Americans, percentiles were calculated using the Hadlock and Eunice
      Kennedy Shriver National Institute of Child Health and Human Development
      race/ethnicity standards (white, black, Hispanic, Asian), and test
      characteristics were calculated for each to predict neonatal morbidity and small
      for gestational age. RESULTS: We included 1514 women, with a mean ultrasonography
      to-delivery interval of 14.4 days (+/-8.8) and a small for gestational age rate
      of 13.6% (n = 206). For the prediction of both composite and severe composite
      neonatal morbidity, the Hadlock method had superior performance, with higher
      areas under the curve than the Eunice Kennedy Shriver National Institute of Child
      Health and Human Development method (P < .001 for both), though neither had good
      discriminatory value (all areas under the curve <0.8). For the prediction of
      small for gestational age at birth, the Hadlock standard had higher sensitivity
      (61.1%) than the Eunice Kennedy Shriver National Institute of Child Health and
      Human Development standard, both when using the interpolated Eunice Kennedy
      Shriver National Institute of Child Health and Human Development method (36.2%, P
      < .01) and the Eunice Kennedy Shriver National Institute of Child Health and
      Human Development whole-week 10th percentile cutoff (46.7%, P < .01). The Hadlock
      method also had a higher area under the curve than the Eunice Kennedy Shriver
      National Institute of Child Health and Human Development interpolated method to
      predict small for gestational age (0.89 vs 0.88, P < .01). The Hadlock method had
      a lower ultrasound-birthweight percentile discrepancy than the Eunice Kennedy
      Shriver National Institute of Child Health and Human Development method (6.1 vs
      16.5 percentile points, P < .01). Fetuses classified as growth restricted by
      Hadlock but not Eunice Kennedy Shriver National Institute of Child Health and
      Human Development had significantly higher composite morbidity than normally
      grown fetuses. Among Native American women, the Hadlock method had the highest
      area under the curve to predict composite and severe composite morbidity, while
      the Hadlock and all Eunice Kennedy Shriver National Institute of Child Health and
      Human Development race-/ethnicity-specific methods performed comparably to
      predict small for gestational age. CONCLUSION: Despite its publication >25 years
      ago, the Hadlock standard is superior to the Eunice Kennedy Shriver National
      Institute of Child Health and Human Development race-/ethnicity-specific standard
      for the prediction of both neonatal morbidity and small for gestational age.

PMID- 30118690
TI  - Persistence of elevated betaHCG after uterine curettage: unexpected diagnosis for
      a young woman.

PMID- 30118691
TI  - The case for magnetic resonance imaging in bowel obstruction during pregnancy:
      Intussusception in a pregnant woman with Roux-en-Y gastric bypass.

PMID- 30118692
TI  - Guidelines for intraoperative care in cesarean delivery: Enhanced Recovery After
      Surgery Society Recommendations (Part 2).
AB  - The Enhanced Recovery After Surgery Society guideline for intraoperative care in
      cesarean delivery will provide best practice, evidenced-based, recommendations
      for intraoperative care, with primarily a maternal focus. The "focused" pathway
      process for scheduled and unscheduled cesarean delivery for this Enhanced
      Recovery After Surgery cesarean delivery guideline will consider procedure from
      the decision to operate (starting with the 30-60 minutes before skin incision)
      through the surgery. The literature search (1966-2017) used Embase and PubMed to
      search medical subject headings including "cesarean section," "cesarean section,"
      "cesarean section delivery," and all pre- and intraoperative Enhanced Recovery
      After Surgery items. Study selection allowed titles and abstracts to be screened
      by individual reviewers to identify potentially relevant articles. Metaanalyses,
      systematic reviews, randomized controlled studies, nonrandomized controlled
      studies, reviews, and case series were considered for each individual topic.
      Quality assessment and data analyses evaluated the quality of evidence and
      recommendations were evaluated according to the Grading of Recommendations,
      Assessment, Development and Evaluation system as used and described in previous
      Enhanced Recovery After Surgery Society guidelines. The Enhanced Recovery After
      Surgery cesarean delivery guideline/pathway has created a maternal focused
      pathway (for scheduled and unscheduled surgery starting from 30-60 minutes before
      skin incision to maternal discharge) with Enhanced Recovery After Surgery
      directed preoperative elements, intraoperative elements, and postoperative
      elements. Specifics of the intraoperative care included the use of prophylactic
      antibiotics before the cesarean delivery, appropriate patient warming
      intraoperatively, blunt expansion of the transverse uterine hysterotomy, skin
      closure with subcuticular sutures, and delayed cord clamping. A number of
      specific elements of intraoperative care of women who undergo cesarean delivery
      are recommended based on the evidence. The Enhanced Recovery After Surgery
      Society guideline for intraoperative care in cesarean delivery will provide best
      practice, evidenced-based, recommendations for intraoperative care with primarily
      a maternal focus. When the cesarean delivery pathway (elements/processes) is
      studied, implemented, audited, evaluated, and optimized by maternity care teams,
      this will create an opportunity for the focused and optimized areas of care and
      recommendations to be further enhanced.

PMID- 30118694
TI  - Prevalence of endometrial cancer or atypical hyperplasia diagnosed incidentally
      in infertility clinic.

PMID- 30118693
TI  - Comparison of the Hadlock and INTERGROWTH formulas for calculating estimated
      fetal weight in a preterm population in France.
AB  - BACKGROUND: Accurate estimation of fetal weight is needed for growth monitoring
      and decision-making in obstetrics; the INTERGROWTH project developed an estimated
      fetal weight formula to construct new intrauterine growth standards. OBJECTIVE:
      We sought to compare the accuracy of the Hadlock and INTERGROWTH formulas for the
      estimation of fetal weight among preterm infants. STUDY DESIGN: Using the EPIPAGE
      2 population-based study of births between 22-34 weeks of gestation, we included
      578 nonanomalous singleton fetuses with an ultrasound-to-delivery interval <2
      days. We used abdominal circumference, head circumference, and femur length to
      calculate estimated fetal weight with Hadlock formula and abdominal and head
      circumferences to calculate estimated fetal weight according to INTERGROWTH. The
      mean percentage errors and the proportions of estimated fetal weight measures
      within +/-10% of birthweight were compared between the 2 methods. RESULTS: Mean
      (SD) gestational age and birthweight were 29.1 (SD 2.7) weeks and 1219 (SD 489)
      g. Mean (SD) percentage errors for Hadlock and INTERGROWTH were significantly
      different: -0.7 (SD 10.1) and -3.5 (SD 11.6), respectively (P < .001), and more
      infants were classified within +/-10% of their birthweight with Hadlock compared
      to INTERGROWTH (68.7% vs 57.8%, P < .001). The INTERGROWTH formula overestimated
      birthweight at 22-23 weeks compared to Hadlock [mean errors of 18.8 (SD 13.6) vs
      5.5 (SD 10.2)] and underestimated birthweight >28 weeks: at 29-31 weeks, mean
      errors were -5.8 (SD 10.9) for INTERGROWTH and -0.6 (SD 10.4) for Hadlock.
      CONCLUSION: Hadlock estimated fetal weight formula was more accurate than
      INTERGROWTH formula for fetuses delivered between 22-34 weeks of gestation. Our
      results support continued use of Hadlock formula in France and raise questions
      about the applicability of INTERGROWTH intrauterine growth standards.

PMID- 30118695
TI  - Mechanism of TRIM25 mediated ubiquitination of metastasis associated protein
      (MTA) 1 in normal liver cells.
AB  - Ninety percent of all cancer related deaths happen due to metastatic progression.
      One important protein facilitating metastatic progression in hepatocellular
      carcinoma (HCC) is the metastasis associated 1 protein (MTA-1). We have earlier
      shown that in the context of HCC and normal liver cell lines, HuH6 and THLE-2,
      respectively. MTA-1 protein is actively stabilized in HCC cell lines and actively
      degraded in normal liver cells. We had also shown that TRIM25 is the E3 ligase
      that interacts with and degrades MTA-1 protein in normal liver cells. However,
      the exact mechanism by which TRIM25 degrades MTA-1 protein has still not been
      elucidated. In the study, we used both in situ prediction algorithms and mass
      spectrometry based post-translational modification analysis to map the lysine
      residues in MTA-1 that are polyubiquitinated. Whereas UbPred algorithm revealed a
      combination of medium and low confidence sites, it revealed only one high
      confidence lysine (K98) residue. The hCKSAAP_UbSite algorithm also predicted K98
      site. Mass spectrometry analysis also showed that K98 has ubiquitin modification.
      Immunofluorescence analysis showed that in normal liver cell line, THLE-2, which
      has high expression of TRIM25, ectopically expressed FLAG-tagged wild-type MTA-1
      was actively degraded, but the K98R mutant MTA-1 was not. In vitro ubiquitination
      assay using recombinant wild-type and K98R mutant MTA-1 confirmed that MTA-1 is
      poly-ubiquitinated at K98 residue by TRIM25. The K98R mutant had a longer half
      life than wild-type MTA-1 protein in an in vitro protein stability assay. We
      establish that TRIM25 ubiquitinates MTA-1 at lysine 98 and degrades it normal
      liver cells.

PMID- 30118696
TI  - Regulation of connexin 43 expression in human gingival fibroblasts.
AB  - AIMS: Abundance of connexin 43 (Cx43), a transmembrane protein that forms
      hemichannels (HCs) and gap junctions (GJs), is dynamically regulated in human
      gingival fibroblasts (GFBLs) during wound healing. This may be important for fast
      and scarless gingival wound healing as Cx43 is involved in key cell functions
      important during this process. Our aim was to uncover the factors that regulate
      Cx43 expression and abundance in GFBLs. We hypothesized that cytokines and growth
      factors released during wound healing coordinately regulate Cx43 abundance in
      GFBLs. RESULTS: TGF-beta1, -beta2, -beta3, PGE2 and IL-1beta significantly
      upregulated, while TNF-alpha and IFN-gamma downregulated Cx43 in cultured GFBLs.
      TGF-beta1, -beta2, -beta3, IL-1beta and IFN-gamma modulated Cx43 abundance at
      both mRNA and protein levels, while TNF-alpha and PGE2 regulated only Cx43
      protein abundance, suggesting involvement of distinct transcriptional/post
      transcriptional and translational/post-translational mechanisms, respectively.
      TGF-beta1-induced upregulation of Cx43 was mediated by TGFbetaRI (ALK5) and
      SMAD2/3 signaling, and this was potently suppressed by PGE2, IL-1beta, TNF-alpha
      and IFN-gamma that inhibited SMAD2/3 phosphorylation. CONCLUSION: Regulation of
      Cx43 abundance in GFBLs involves transcriptional/post-transcriptional and
      translational/post-translational mechanisms that are distinctly modulated by an
      interplay between TGF-beta isoforms and PGE2, IL-1beta, TNF-alpha and IFN-gamma.

PMID- 30118697
TI  - BRMS1L suppresses ovarian cancer metastasis via inhibition of the beta-catenin
      wnt pathway.
AB  - A low level of breast cancer metastasis suppressor 1-like (BRMS1L) has been
      implicated in tumour metastasis involving breast cancer and other cancers. It
      remains unclear whether BRMS1L is involved in epithelial ovarian cancer (EOC)
      metastasis and what the molecular mechanism of BRMS1L is in suppressing EOC
      metastasis. In this study, we examined the mRNA expression and protein level of
      BRMS1L by screening EOC patients. Our results show that BRMS1L expression is
      downregulated in EOC patients compared to that in normal people and negatively
      correlated to pathological stages of EOC. We further explored examining
      epithelial to mesenchymal transition (EMT) as the molecular mechanism of BRMS1L
      in cancer cell metastasis. The overexpression of BRMS1L inhibits EOC cell
      migration and invasion, and this inhibition is correlated to the inactivation of
      EMT and Wnt/beta-catenin signalling in vitro. Knockdown of BRMS1L by shRNA
      promotes EOC metastasis, enhances EMT process and activates Wnt/beta-catenin
      signalling. These results suggest that BRMS1L plays a critical role in the
      suppression of ovarian cancer metastasis, and BRMS1L can be considered as a
      prognostic biomarker and potential therapeutic target for EOC patients.

PMID- 30118698
TI  - An insight into the ecobiology, vector significance and control of Hyalomma ticks
      (Acari: Ixodidae): A review.
AB  - Ticks (Acari:Ixodoidea) are important ectoparasites infesting livestock and human
      populations around the globe. Ticks can cause damage directly by affecting the
      site of infestation, or indirectly as vectors of a wide range of protozoa,
      bacteria and viruses which ultimately lead to lowered productivity of livestock
      populations. Hyalomma is a genus of hard ticks, having more than 30 species well
      adapted to hot, humid and cold climates. Habitat diversity, vector ability, and
      emerging problem of acaricidal resistance in enzootic regions typify this genus
      in various countries around the world. This paper reviews the epidemiology,
      associated risk factors (temperature, climate, age, sex, breed etc.), vector
      role, vector-pathogen association, and reported control strategies of genus
      Hyalomma. The various proteins in saliva of Hyalomma secreted into the blood
      stream of host and the prolonged attachment are responsible for the successful
      engorgement of female ticks in spite of host immune defense system. The various
      immunological approaches that have been tried by researchers in order to cause
      tick rejection are also discussed. In addition, the novel biological control
      approaches involving the use of entomo-pathogenic nematodes and Bacillus
      thuringiensis (B. thuringiensis) serovar thuringiensis H14; an endotoxin, for
      their acaricidal effect on different species and life cycle stages of Hyalomma
      are also presented.

PMID- 30118699
TI  - Widespread occurrence of Cryptosporidium infections in patients with HIV/AIDS:
      Epidemiology, clinical feature, diagnosis, and therapy.
AB  - Cryptosporidium infection is a serious threat for HIV/AIDS patients, causing
      severe diarrhea and even death. The overall prevalence of Cryptosporidium in
      HIV/AIDS patients was calculated as approximately 8.69% (7,799/89,724), with
      higher prevalence observed in individuals with diarrhea, individuals with low
      CD4+ T-lymphocyte counts, and antiretroviral therapy-naive individuals.
      Cryptosporidium infection was not significantly associated with patient age or
      gender, national development levels, or continent of residence. Over the period
      from 2007 to 2017, Cryptosporidium prevalence was 10.09% (3,282/32,517); this
      figure was higher than that observed in each of the previous observation periods
      (1985-1995 and 1996-2006), suggesting that the prevalence of cryptosporidiosis
      has been increasing over time in HIV/AIDS patients. Ten Cryptosporidium species
      and genotypes have been identified from 1,252 isolates, with C. hominis, C.
      parvum, and C. meleagridis accounting for 93.53% of infections. Five subtypes
      each of C. hominis (Ia, Ib, Id, Ie, and If), C. parvum (IIa to IIe), and C.
      meleagridis (IIIa to IIIe) have been described by sequence analyses of the 60-kDa
      glycoprotein (gp60) gene. Variation in the clinical manifestations observed in
      HIV/AIDS patients might be attributed to infection by different Cryptosporidium
      species, genotypes and subtypes, as well as different sites of infection. New
      molecular and immunological diagnostic techniques are in development or already
      commercially available. High-throughput screening methods for development of new
      or repurposed therapeutics as well as novel parasite genetic manipulation
      strategies offer hope for improving human cryptosporidiosis therapies.
      Painstaking efforts by researchers as well as support from governments and
      funding agencies will be required to make lasting achievements in this field.

PMID- 30118700
TI  - Japanese encephalitis in Indonesia: An update on epidemiology and transmission
      ecology.
AB  - The Japanese Encephalitis (JE) virus circulation in Indonesia was first
      documented in Lombok in 1960, and the virus was first isolated in 1972 from Culex
      tritaeniorhynchus in Bekasi, West Java and Kapuk, West Jakarta. Since then,
      Indonesia has been recognized as an endemic country for JE transmission. Up to
      now, JE cases have been found in at least 29 provinces, with Bali, West
      Kalimantan, East Nusa Tenggara, West Java and East Java, being the areas of
      highest incidence. However, routine surveillance on JE has not been established
      at the national level even though many surveys were conducted. JEV has been
      isolated from 10 mosquito species: Culex tritaeniorhynchus, Cx. gelidus, Cx.
      vishnui, Cx. fuscocephala, Cx. bitaeniorhynchus, Cx. quinquefasciatus, Anopheles
      vagus, An. kochi, An. annularis, and Armigeres subalbatus. Culex
      tritaeniorhynchus is the main JE vector in Indonesia. JE has been detected
      throughout the Indonesian archipelago from West to East. However, due to a lack
      of routine, systematic and standardized diagnostic approaches, the JE burden has
      still not been clearly established yet. Long term and systematic JE surveillance
      across Indonesia is a priority, the burden needs to be better assessed and
      appropriate control measures must be implemented.

PMID- 30118701
TI  - Mapping the potential distributions of etiological agent, vectors, and reservoirs
      of Japanese Encephalitis in Asia and Australia.
AB  - Japanese encephalitis virus (JEV) is a substantial cause of viral encephalitis,
      morbidity, and mortality in South-East Asia and the Western Pacific. World Health
      Organization recognized Japanese Encephalitis (JE) as a public health priority in
      demands to initiate active vaccination programs. Recently, the geographic
      distribution of JEV has apparently expanded into other areas in the Pacific
      islands and northern Australia; however, major gaps exist in knowledge in regard
      to its current distribution. Here, we mapped the potential distribution of
      mosquito vectors of JEV (Culex tritaeniorhynchus, Cx. pseudovishnui, Cx. vishnui,
      Cx. fuscocephala, Cx. gelidus), and reservoirs (Egretta garzetta, E. intermedia,
      Nycticorax nycticorax) based on ecological niche modeling approach. Ecological
      niche models predicted all species to occur across Central, South and South East
      Asia; however, Cx. tritaeniorhynchus, E. garzetta, E. intermedia, and N.
      nycticorax had broader potential distributions extending west to parts of the
      Arabian Peninsula. All predictions were robust and significantly better than
      random (P < 0.001). We also tested the JEV prediction based on 4335 additional
      independent human case records collected by the Chinese Information System for
      Disease Control and Prevention (CISDCP); 4075 cases were successfully predicted
      by the model (P < 0.001). Finally, we tested the ecological niche similarity
      among JEV, vector, and reservoir species and could not reject any of the null
      hypotheses of niche similarity in all combination pairs.

PMID- 30118703
TI  - Detection of three common mutations causing beta-thalassemia by using a closed
      tube multiplex PCR.
AB  - Small oligonucleotides mutations are the large majority causes of beta
      thalassemia. Dual priming oligonucleotide PCR has been used to detect point
      mutations and thus could be applied to diagnose beta-thalassemia. The goal of
      this study was to establish a simple, quick and cost-effective screening assay by
      using modified dual priming oligonucleotide PCR for three most common mutations
      of beta-thalassemia [CD71-72 (+A), CD 41-42 (-CTTT), Pnt.-28 (A -> G)] in
      Southeast Asia and southern China. Man-made 5 tandem mismatched bases instead of
      poly (I) were used as the linker in the specific PCR primers. Single closed-tube
      multiplex PCRs followed by dissociation curve (DC) analysis were included in the
      molecular screening assay. Denaturing high-performance liquid chromatography
      analysis was applied to distinguish compound heterozygotes from single mutations.
      A blinded study of 91 samples was performed using this new assay. There were 41
      samples detected as the above three mutations and it was concordant with the
      original methods. In conclusion, the modified dual priming oligonucleotide
      multiplex PCR/DC can detect these three genotypes of common mutation of beta
      thalassemia; this method is simple, rapid and cost-effective, which makes it
      suitable for large-scale screening and diagnosis.

PMID- 30118704
TI  - Anomalous Left Internal Mammary Artery: A Cardiologist's Conundrum.

PMID- 30118705
TI  - Less Is More in Post Pediatric Heart Transplant Care (Commentary).

PMID- 30118702
TI  - HDL activates expression of genes stimulating cholesterol efflux in human
      monocyte-derived macrophages.
AB  - High density lipoproteins (HDL) are key components of reverse cholesterol
      transport pathway. HDL removes excessive cholesterol from peripheral cells,
      including macrophages, providing protection from cholesterol accumulation and
      conversion into foam cells, which is a key event in pathogenesis of
      atherosclerosis. The mechanism of cellular cholesterol efflux stimulation by HDL
      involves interaction with the ABCA1 lipid transporter and ensuing transfer of
      cholesterol to HDL particles. In this study, we looked for additional proteins
      contributing to HDL-dependent cholesterol efflux. Using RNAseq, we analyzed mRNAs
      induced by HDL in human monocyte-derived macrophages and identified three genes,
      fatty acid desaturase 1 (FADS1), insulin induced gene 1 (INSIG1), and the low
      density lipoprotein receptor (LDLR), expression of which was significantly
      upregulated by HDL. We individually knocked down these genes in THP-1 cells using
      gene silencing by siRNA, and measured cellular cholesterol efflux to HDL. Knock
      down of FADS1 did not significantly change cholesterol efflux (p = 0.70), but
      knockdown of INSIG1 and LDLR resulted in highly significant reduction of the
      efflux to HDL (67% and 75% of control, respectively, p < 0.001). Importantly, the
      suppression of cholesterol efflux was independent of known effects of these genes
      on cellular cholesterol content, as cells were loaded with cholesterol using
      acetylated LDL. These results indicate that HDL particles stimulate expression of
      genes that enhance cellular cholesterol transfer to HDL.

PMID- 30118706
TI  - Lung Cancer Screening Feasibility Beyond High Specialized Centers.

PMID- 30118707
TI  - Multiple Recurrent Cardiac Myxomas with Protein Kinase A regulatory Subunit
      1alpha Gene Mutation.
AB  - Multiple recurrent cardiac myxomas are quite rare in clinical practice. A young
      male patient had four times of myxoma occurrence, with two times in the left
      atrium and two times in the left ventricle. He had no medical history of
      cardiovascular diseases, familial cardiac neoplasm, and endocrinopathy. He
      underwent surgical resection four times. Genetic analysis revealed a heterozygous
      base pair mutation in the gene of protein kinase A regulatory subunit 1alpha
      (PRKAR1A) at chromosome 17 in both peripheral blood mononuclear cells and myxoma
      tissues. Postoperative regular examination is recommended for patients with
      cardiac myxoma.

PMID- 30118709
TI  - Invited Commentary.

PMID- 30118708
TI  - Impact of Arteriovenous Fistula for Hemodialysis on Clinical Outcomes of Coronary
      Artery Bypass.
AB  - BACKGROUND: This study compared clinical outcomes between the use of in situ and
      free internal thoracic artery grafts in patients with upper extremity
      arteriovenous fistula who underwent coronary artery bypass. METHODS: We reviewed
      85 hemodialysis-dependent patients with upper extremity arteriovenous fistula who
      underwent coronary artery bypass with internal thoracic artery grafts. The
      patients were categorized into 2 groups; 48 (56%) with in situ graft ipsilateral
      to the arteriovenous fistula (group I) and 37 (44%) with free grafts anastomosed
      to the ascending aorta (group F). The follow-up period was 32.0 +/- 38.1 months.
      RESULTS: The estimated overall survival rates at 3, 5, and 10 years were 89.5%,
      81.6%, and 53%, respectively, for all discharged patients. There was no
      significant difference in in-hospital mortality, all-cause mortality, and freedom
      from major adverse cardiac events between the groups, although cardiac-related
      deaths occurred only in group I (n = 5). Ipsilateral in situ grafts were
      associated with hemodialysis-induced chest pain (odds ratio, 5.528; 95%
      confidence interval, 1.079 to 28.333; p = 0.040). The incidence of dialysis
      induced chest pain in patients with in situ noncomposite, in situ composite, and
      free grafts was 45.5%, 19.4%, and 5.7%, respectively (p = 0.009). CONCLUSIONS:
      Mortality was not influenced by using the internal thoracic artery as an
      ipsilateral in situ graft in patients with upper extremity arteriovenous fistula.
      However, there was a risk of increased incidence of hemodialysis-induced chest
      pain that is most likely related to coronary steal. A free internal thoracic
      artery graft would be an alternative option in these patients.

PMID- 30118710
TI  - En Bloc Left Pulmonary Vein and Appendage Isolation in Thoracoscopic Surgery for
      Atrial Fibrillation.
AB  - BACKGROUND: We evaluated the safety and rhythm control effectiveness in en bloc
      isolation of the left pulmonary vein (PV) and appendage conducted as part of the
      thoracoscopic procedure for bilateral PV isolation, non-PV ablation, and
      appendage closure for atrial fibrillation (AF). METHODS: Procedural safety was
      evaluated by reviewing the surgical records. Rhythm control was examined in
      accordance with the Heart Rhythm Society guidelines at postoperative months 1, 3,
      6, and 12, and yearly thereafter. The sinus rhythm rates at postoperative years 1
      and 2 were compared with the corresponding data from our previous procedure
      without the en bloc technique. RESULTS: Starting in 2014, the en bloc technique
      was applied to 238 nonvalvular AF patients and successfully performed in all but
      23 patients. The mean operation time was 88 minutes. There were no hospital
      deaths or major procedure-related complications. The mean follow-up period was
      1.7 years. The sinus rhythm rates at postoperative years 1 and 2 were 85% and 80%
      in paroxysmal, 76% and 70% in persistent, and 67% and 61% in long-standing
      persistent AF, respectively, without antiarrhythmic drug use. Compared with the
      previous procedure (n = 324), sinus rhythm rates were higher in long-standing
      persistent AF (67% vs 50% at 1 year and 61% vs 40% at 2 years; p = 0.04). No
      patients suffered cardiogenic thromboembolisms without anticoagulation.
      CONCLUSIONS: Thoracoscopic en bloc left PV and appendage isolation was safely
      achieved in most patients. Using this technique may contribute to better rhythm
      control results than not using it in cases of long-standing persistent AF.

PMID- 30118711
TI  - Vasoplegia After Surgical Left Ventricular Restoration: 2-Year Follow-Up.
AB  - BACKGROUND: Vasoplegia is a severe complication that can develop after surgical
      procedures for heart failure. The current study evaluated the effect of
      vasoplegia on survival, cardiac function, and renal function 2 years after
      surgical left ventricular restoration (SVR). METHODS: Heart failure patients with
      a left ventricular ejection fraction (LVEF) of 0.35 or less who underwent SVR in
      2006 to 2014 were included. Vasoplegia was defined as the continuous need of
      vasopressors (norepinephrine >=0.2 MUg . kg-1 . min-1 or terlipressin [any dose],
      or both) combined with a cardiac index of 2.2 L . min-1 . m-2 or higher for at
      least 12 consecutive hours, starting within the first 3 days postoperatively. The
      effect of vasoplegia on mortality, New York Heart Association Functional
      Classification, LVEF, and creatinine clearance was assessed up to 2 years of
      follow-up. RESULTS: SVR was performed in 113 patients (80% men), aged 62 +/- 10
      years, and with an LVEF of 0.25 +/- 0.06. Postoperative vasoplegia developed in
      23%. Survival was lower in patients with vasoplegia compared with patients
      without vasoplegia at 6 months (62% vs 90%, p = 0.001) and at 2 years (50% versus
      84%, p < 0.001). At the 2-year follow-up, New York Heart Association class and
      LVEF had improved and were similar in both groups (respectively, p = 0.319 and p
      = 0.444). Creatinine clearance was lower in patients with vasoplegia compared
      with patients without vasoplegia 2 years postoperatively (p < 0.001), even after
      correcting for baseline creatinine clearance (p = 0.009). CONCLUSIONS: Vasoplegia
      after SVR is associated with decreased survival. Despite an improved and similar
      cardiac function, renal function was compromised in vasoplegic patients at the 2
      year follow-up.

PMID- 30118712
TI  - Perioperative Outcomes for Stage I Non-Small Cell Lung Cancer: Differences
      Between Men and Women.
AB  - BACKGROUND: Previous studies have highlighted important biologic and survival
      related differences among men and women with non-small cell lung cancer (NSCLC).
      However, differences in perioperative or short-term outcomes have not been as
      well characterized. In this study, we investigated differences in the
      perioperative period and postoperative emergency department (ED) visits among men
      and women after lobectomy for stage I NSCLC. METHODS: A retrospective review was
      performed of patients who underwent a lobectomy for clinical stage I NSCLC at a
      single institution from 2010 to 2015. RESULTS: We identified 559 patients for
      inclusion, including 293 women (52%) and 266 men (48%). Women were more likely to
      present with clinical T1 status (p = 0.005) and to undergo a minimally invasive
      operation (p = 0.058). To reduce confounding, 206 case-matched pairs were
      identified. After matching, no differences were found in length of stay (p =
      0.551) or pulmonary complications (p = 0.509); however, men experienced more
      cardiac complications (18% versus 7%, p = 0.001). Of importance, although rates
      of 30- and 90-day ED visits between sexes were similar (p = 0.531, p = 0.890,
      respectively) and no sex-related differences were found in presenting symptom on
      return to the ED (p = 0.478), women were more likely to be readmitted after
      presenting to the ED within 30 days (p = 0.038). CONCLUSIONS: Women demonstrated
      an increased likelihood of being admitted after presenting to the ED within 30
      days after discharge, indicating important differences between men and women in
      the short-term period after lobectomy. Further research will be required to
      further understand the cause for these differences.

PMID- 30118713
TI  - Invited Commentary.

PMID- 30118714
TI  - A Hybrid Maze Procedure for Long-Standing Persistent Atrial Fibrillation.
AB  - BACKGROUND: Catheter ablation (CA) for long-standing persistent atrial
      fibrillation (LSPAF) is suboptimal and open surgical ablation, while more
      successful, is too invasive to be a first-line therapy. Less invasive hybrid
      procedures that combine thoracoscopic surgery (TS) with CA have been only
      marginally more successful for LSPAF than CA alone. METHODS: Joint hybrid
      procedures for LSPAF are based on the assumption that AF surgery and CA
      procedures can be guided by intraoperative mapping. However, intraoperative
      mapping is not always dependable because of the transient nature of the
      sustaining reentrant drivers. The best results in patients with LSPAF have been
      attained with the non-guided, anatomy-based surgical Maze-IV procedure. Likewise,
      a staged TS/CA hybrid procedure that creates a combination of lesions that adhere
      to the concept of a maze pattern, i.e., a "Hybrid Maze-IV Procedure", should be
      more effective for LSPAF. RESULTS: Initial TS includes all lesions of the Maze-IV
      procedure except the mitral line, coronary sinus lesion, and one right atrial
      lesion. Follow-up CA at 3 months includes "touching up" any incomplete TS
      lesions, a cavo-tricuspid isthmus lesion, and a mitral line/coronary sinus lesion
      in the 10-15% of patients with post-TS peri-mitral flutter. This combination of
      TS and CA lesions creates a complete Maze-IV procedure. CONCLUSIONS: It is
      possible to create the complete lesion pattern of a Maze-IV procedure with a
      staged TS/CA hybrid procedure. The success of this "Hybrid Maze Procedure" in
      patients with LSPAF should be the same as that attained with an open surgical
      Maze-IV procedure.

PMID- 30118715
TI  - Giant Aneurysm of the Ascending Aorta Requiring Emergency Repair in a Newborn
      Baby.
AB  - Congenital aneurysm of the ascending aorta is a rare cardiovascular pathology and
      usually associated with well-known connective tissue disorders. In this report,
      we present an idiopathic ascending aortic aneurysm extending to the aortic arch
      in an antenatally diagnosed newborn whom required immediate surgical treatment
      due to the rapid progression of aneurysm size at the age of 1 day.

PMID- 30118716
TI  - Circulating APP, NCAM and Abeta serve as biomarkers for Alzheimer's disease.
AB  - Alzheimer's disease (AD) is the most common neurodegenerative disease and the
      early diagnosis and intervention are important for valid treatment of AD.
      However, there are few biomarkers for the diagnosis and monitoring of AD. In the
      present study, circulating APP, NCAM, Abeta40, and Abeta42 were measured in order
      to identify which marker or combination of markers could be useful, cost
      effective and noninvasive biomarkers for diagnosing and continuously monitoring
      AD. The results showed that circulating APP, NCAM, Abeta40, and Abeta42 were
      different between the AD group and the control group. Importantly, the
      combination of the four biomarkers had the highest AUC (0.997) with the highest
      sensitivity (98.5). Therefore, circulating APP, NCAM, Abeta40, and Abeta42 can be
      used as desirable biomarkers for AD diagnosis and monitoring.

PMID- 30118717
TI  - Medial habenula maturational deficits associate with low motivation for voluntary
      physical activity.
AB  - The habenula is a small, diencephalic structure comprised of distinct subnuclei
      which receives inputs from the limbic forebrain and sends projections to various
      regions in the midbrain, making this region well positioned to influence reward
      and motivation. Genetic ablation of the dorsal medial habenula is known to
      decrease voluntary wheel-running in mice. However, the extent to which the medial
      habenula (MHb) mediates wheel-running motivation in the context of high or low
      motivation for voluntary physical activity remains to be determined. In so, we
      utilized 5-week-old female rats selectively bred to voluntarily run high (HVR) or
      low (LVR) distances in order to determine if inherent differences in medial
      habenula maturation accompany inherent differences in wheel-running motivation.
      We report a significantly higher expression of genes associated with MHb
      development (Brn3a, Nurr1, Tac1, and Kcnip) in HVR versus LVR rats. Furthermore,
      there was a positive correlation between Brn3a and Nurr1 expression and run
      distance in HVR, but not LVR rats. Similarly, NeuN and Synapsin 1, markers of
      neuronal maturation, were higher in HVR compared to LVR rats. Lastly, dendritic
      density was determined to be higher in the MHb of HVR versus LVR rats, while LVR
      rats showed a higher percentage of thin spines, suggesting a higher prevalence of
      immature dendrites in LVR rats. Taken together, the above findings highlight the
      involvement of MHb in driving the motivation to be physically active. Given
      pandemic levels of global physical inactivity, the role of the MHb offers a novel
      potential to improve our global health.

PMID- 30118718
TI  - Influence of hippocampal low-frequency stimulation on GABAA R alpha1, ICER and
      BNDF expression level in brain tissues of amygdala-kindled drug-resistant
      temporal lobe epileptic rats.
AB  - This study investigated the therapeutic effect of hippocampal low-frequency
      stimulation (Hip-LFS) and its influence on the type A gamma-aminobutyric acid
      receptor alpha1 subunit (GABAA R alpha1 subunit), inducible cAMP early repressor
      (ICER) and brain-derived neurotrophic factors (BNDF). The model of epilepsy was
      induced by chronic electrical stimulation in amygdala. Drug-resistant and drug
      sensitive epileptic rats were selected by testing their seizure response to
      phenytoin and phenobarbital. The changes of GABAA R alpha1 subunit, ICER and BDNF
      expression were detected via immunohistochemistry and western blot. The
      expression levels of ICER and BDNF were increased remarkably but the GABAA R
      alpha1 subunit decreased significantly in the drug-resistant epileptic rats.
      However, the expression levels of ICER, BDNF were decreased and the expression of
      the GABAA R alpha1 subunit increased significantly in the drug-resistant
      epileptic rats after two weeks of Hip-LFS. Meanwhile, the seizure degree was
      reduced and the electroencephalograms were improved. The present study
      demonstrated thatincreased ICER and BDNF might be associated with the development
      of drug-resistance. The effect of Hip-LFS in the treatment of drug-resistant
      epileptic rats might be associated with increasing the levels of the ICER and the
      BDNF.

PMID- 30118719
TI  - Uncertainty, Imprecision, and Many-Valued Logics in Protein Bioinformatics.
AB  - Understanding proteins, their structures, functions, mutual interactions,
      activity in cellular reactions, interactions with drugs, and expression in body
      cells is a key to efficient medical diagnosis, drug production, and treatment of
      patients. Machine learning and data exploration methods supported by many-valued
      logics allow to grasp the imprecision and uncertainties that naturally occur in
      proteins and other biomolecules. Many-valued logics, like Lukasiewicz logic or
      fuzzy logic, are non-classical logics that do not restrict the number of truth
      values to only two values of true or false, but they allow for a larger set of
      truth degrees. In this paper, we briefly review the use of many-valued logics,
      especially the fuzzy logic, in bioinformatics. Then, we focus on protein
      bioinformatics, and present selected applications of many-valued logics in the
      analysis of complex protein structures, including; (1) potential-based protein
      similarity searching, (2) matching proteins on the basis of secondary structures,
      (3) 3D protein structure alignment, (4) prediction of intrinsically disordered
      proteins, and (5) fuzzy querying in large collections of Big macromolecular Data.
      Results of presented studies show that the utilization of many-valued logics can
      enrich the investigations of protein molecules, in which uncertainty and
      imprecision are prevalent problems. The paper discusses all observed benefits
      brought by the application of many-valued logics in investigations related to
      selected protein analyzes carried out by the author.

PMID- 30118720
TI  - Impact of intraocular scatter on stereopsis.
AB  - To investigate the effect of intraocular scatter on stereopsis, we measured
      stereoacuity with scatter either remaining at the natural eye-induced level or
      further enhanced by a set of three different scatter filters. Stereo thresholds
      at different viewing durations were obtained using a psychophysical method of
      constant stimuli. The results indicate that stereoacuity was degraded with a
      binocular increase in scatter levels for all the subjects. Measurements were also
      performed in the presence of interocular differences in scatter levels. In this
      case, stereoacuity was found to be even a little worse than that obtained with
      both eyes at a higher scatter level. This suggests that stereoacuity in the
      presence of interocular differences in scatter levels is mainly dependent on the
      higher scatter level.

PMID- 30118721
TI  - Clinical and laboratory skin biomarkers of organ-specific diseases.
AB  - Intense research during the last few years has elucidated a number of mechanisms
      of the complex human aging process. Among the body organs, skin has a
      distinguished role in aging perception both because it constitutes the organ on
      which the first signs of aging are mostly visible and because skin is recognized
      as an indicator of human health. Analogous to all other organs, skin undergoes
      multiple morphological and functional changes with age affected by extrinsic and
      intrinsic factors. Evaluation of skin morphology as well as of advanced glycation
      end products, dermal collagen content and alterations of the Wnt signaling
      pathway may predict - among others - the aging status of the cardiovascular
      system, the brain and the bones. Increasing knowledge on the association of
      certain clinical and laboratory characteristics of extrinsic and intrinsic skin
      aging with organ-specific diseases opens new possibilities for the establishment
      of clinical and laboratory skin biomarkers for systemic human aging and the
      course of several internal, organ-specific diseases.

PMID- 30118722
TI  - Neurocognitive Impairment and Its Long-term Impact on Adults With Congenital
      Heart Disease.
AB  - It is well-recognized now that adult survivors with congenital heart disease
      (ACHD) are at risk for non-cardiac co-morbidities and complications that can
      impact symptoms and clinical outcomes. Cognitive dysfunction, in particular, is
      common in this population, but likely an under-recognized and undertreated cause
      for long-term morbidity. Abnormal cognitive function has a major impact on all
      aspects of quality of life, including employment opportunities, educational
      attainment, and the ability to maintain meaningful social relationships, such as
      marriage. The association and impact of cognitive dysfunction in ACHD is not
      fully understood and continues to be understudied. Nevertheless, cognitive
      dysfunction may be a potentially modifiable risk factor in this population that
      is amenable to intervention, which may in-turn translate to improved outcomes.
      This review summarizes our current understanding of the prevalence, impact, and
      management of cognitive dysfunction in ACHD.

PMID- 30118723
TI  - Challenges and innovations of delivering medicines to older adults.
AB  - Older adults with multimorbidity, polypharmacy, and complex health needs are the
      major consumer of health care. Ensuring that medicines are used safely,
      effectively, and delivered efficiently in this population is challenging. In this
      context, the approach to medicines delivery should seek to overcome some of the
      difficulties of delivering medicines to older people, and ensure each medication
      is delivered by the optimal and most convenient route for the patient in
      question. However, this poses significant obstacles, as the development of
      medicines suitable for use in older populations does not often account for
      complex health needs, potential challenges in relation to drug disposition,
      safety of excipients and limitations with practical usability of dosage forms.
      The objective of this review is to summarise and discuss current challenges and
      novel approaches to delivering medications to older adults.

PMID- 30118724
TI  - A comparison of the Avisoft (5.2) and Ultravox (2.0) recording systems:
      Implications for early-life communication and vocalization research.
AB  - Alterations in early-life communicative behaviors are a common feature of
      neurodevelopmental conditions, such as autism and epilepsy. One method of
      investigating communication in murine models is through analyzing ultrasonic
      vocalizations. These vocalizations are commonly recorded with either the Avisoft
      or the Ultravox recording programs. However, since no study has compared whether
      the systems are equally sensitive, the findings in one program may not be
      reproducible in the other. To directly compare the two programs, we elicited
      vocalizations from male and female 129SvEvTac and C57BL/6 mouse pups via the
      maternal isolation paradigm, recording vocalizations simultaneously with both
      systems. We held the detection parameters identical for each system and found
      that there was only a medium correlation between Avisoft and Ultravox overall.
      Further analysis indicated that Avisoft detected more total vocalizations, as
      well as more vocalizations at the set frequencies of 50, 60, and 70 kHz than
      Ultravox, p <  .05. No statistically significant difference was present at 80
      kHz. These findings demonstrate that different recording systems do not detect
      the same quantity of vocalizations as one another, even when detection parameters
      are congruent. Therefore, it may be useful to revisit previous negative results
      obtained with Ultravox and repeat the experiments using Avisoft. Ultimately,
      ultrasonic vocalizations are a valuable tool, capable of examining early-life
      phenotypes. However, a more thorough understanding of the relationships between
      recording systems is necessary to achieve a more comprehensive and reproducible
      assessment of vocalizing behaviors.

PMID- 30118725
TI  - A systematic review investigating the relationship of electroencephalography and
      magnetoencephalography measurements with sensorimotor upper limb impairments
      after stroke.
AB  - BACKGROUND: Predicting sensorimotor upper limb outcome receives continued
      attention in stroke. Neurophysiological measures by electroencephalography (EEG)
      and magnetoencephalography (MEG) could increase the accuracy of predicting
      sensorimotor upper limb recovery. NEW METHOD: The aim of this systematic review
      was to summarize the current evidence for EEG/MEG-based measures to index neural
      activity after stroke and the relationship between abnormal neural activity and
      sensorimotor upper limb impairment. Relevant papers from databases EMBASE,
      CINHAL, MEDLINE and pubMED were identified. Methodological quality of selected
      studies was assessed with the Modified Downs and Black form. Data collected was
      reported descriptively. RESULTS: Seventeen papers were included; 13 used EEG and
      4 used MEG applications. Findings showed that: (a) the presence of somatosensory
      evoked potentials in the acute stage are related to better outcome of upper limb
      motor impairment from 10 weeks to 6 months post-stroke; (b) an interhemispheric
      imbalance of cortical oscillatory signals associated with upper limb impairment;
      and (c) predictive models including beta oscillatory cortical signal factors with
      corticospinal integrity and clinical measures could enhance upper limb motor
      prognosis. COMPARING WITH EXISTING METHOD: The combination of neurological
      biomarkers with clinical measures results in higher statistical power than using
      neurological biomarkers alone when predicting motor recovery in stroke.
      CONCLUSIONS: Alterations in neural activity by means of EEG and MEG are
      demonstrated from the early post-stroke stage onwards, and related to
      sensorimotor upper limb impairment. Future work exploring cortical oscillatory
      signals in the acute stage could provide further insight about prediction of
      upper limb sensorimotor recovery.

PMID- 30118727
TI  - The subfornical organ in sodium appetite: Recent insights.
AB  - To maintain sodium homeostasis, animals will readily seek and ingest salt when
      salt-depleted, even at concentrations that they typically find aversive when
      sodium replete. This innate behaviour is known as sodium (or salt) appetite. Salt
      appetite is subserved by a conserved brain network that senses sodium need and
      promotes the ingestion of salty substances when sodium-deficient. The subfornical
      organ (SFO) is a circumventricular organ that has diverse roles encompassing
      cardiovascular regulation, energy balance, immune responses, reproduction, and
      hydromineral balance. The SFO acts as a central sensor of sodium need and is
      essential for the generation of salt appetite. In this review, we discuss recent
      findings on the neurochemical and circuit-level organisation of the SFO in the
      context of sodium appetite.

PMID- 30118726
TI  - Managing emerging mutagenicity risks: Late stage mutagenic impurity control
      within the atovaquone second generation synthesis.
AB  - The mutagenic-impurity control strategy for a second generation manufacturing
      route to the non-mutagenic antipneumocystic agent atovaquone (2-((1R,4R)-4-(4
      chlorophenyl)cyclohexyl)-3-hydroxynaphthalene-1,4-dione) 1 is described.
      Preliminary assessment highlighted multiple materials of concern which were
      largely discharged either through returning a negative bacterial mutagenicity
      assay or through confidence that the impurity would be purged during the
      downstream processing from when it was first introduced. Additional genotoxicity
      testing highlighted two materials of concern where initial assessment suggested
      that testing for these impurities at trace levels within the drug substance would
      be required. Following a thorough review of process purging detail, spiking and
      purging experimentation, and an understanding of the process parameters to which
      they were exposed an ICH M7 Option 4 approach could be justified for their
      control. The development of two 1H NMR spectroscopy methods for measurement of
      these impurities is also described as well as a proposed summary table for
      describing the underlying rationale for ICH M7 control rationales to regulators.
      This manuscript demonstrates that process purging of potential mutagenic
      impurities can be realised even when they are introduced in the later stages of a
      process and highlights the importance of scientific understanding rather than
      relying on a stage-counting approach.

PMID- 30118728
TI  - School-supervised use of a once-daily inhaled corticosteroid regimen: A cluster
      randomized trial.
AB  - BACKGROUND: School-supervised use of a once-daily inhaled corticosteroid regimen
      (supervised therapy) can improve medication adherence and asthma control.
      OBJECTIVE: We sought to evaluate the effectiveness of supervised therapy in a
      unique setting and population. METHODS: We conducted a cluster randomized trial
      of supervised therapy in 20 elementary schools with a disproportionate enrollment
      of low-income Latino students. Schools were purposively selected, matched, and
      randomized to receive 9 months of supervised therapy with mometasone furoate or
      usual care. All English- or Spanish-speaking students with self-reported asthma
      were eligible. The Asthma Control Questionnaire (ACQ) was interviewer
      administered quarterly at school. Students in supervised therapy schools were
      hypothesized to have lower ACQ scores than students in usual-care schools.
      RESULTS: Of 393 enrolled students, 189 students receiving immediate intervention
      and 143 students receiving delayed intervention provided 1 or more ACQ data
      points, were between 6 and 10 years of age, and were included in the primary
      analysis. At baseline, 39% of students reported taking a controller medication,
      and 24% had well-controlled asthma. Eighty percent of students receiving
      immediate intervention were prescribed mometasone. Schools administered 98% of
      prescribed doses when students attended school. Absences, weekends, and holidays
      reduced calendar adherence to 53%. During the first year, the mean ACQ score for
      students receiving immediate and delayed intervention was 1.55 (95% CI, 1.41
      1.70) and 1.64 (95% CI, 1.47-1.80), respectively. The estimated treatment effect
      was -0.08 (95% CI, -0.31 to 0.14). DISCUSSION: Compared with usual care,
      supervised therapy did not improve asthma control among this population of Latino
      students. Additional research is warranted to confirm these results.

PMID- 30118729
TI  - Estrogen effects on oxytocinergic pathways that regulate food intake.
AB  - Multiple stimulatory and inhibitory neural circuits control eating, and these
      circuits are influenced by an array of hormonal, neuropeptide, and
      neurotransmitter signals. For example, estrogen and oxytocin (OT) both are known
      to decrease food intake, but the mechanisms by which these signal molecules
      influence eating are not fully understood. These studies investigated the
      interaction between estrogen and OT in the control of food intake. RT-qPCR
      studies revealed that 17beta-estradiol benzoate (EB)-treated rats showed a two
      fold increase in OT mRNA in the paraventricular nucleus of the hypothalamus (PVN)
      compared to Oil-treated controls. Increased OT mRNA expression may increase OT
      protein levels, and immunohistochemistry studies showed that EB-treated rats had
      more intense OT labeling in the nucleus of the solitary tract (NTS), a region
      known to integrate signals for food intake. Food intake measurements showed that
      EB treatment reduced food intake, as expected. EB-treated rats lost weight over
      the course of the experiment, as expected, and EB-treated rats that received the
      highest dose of OT lost more weight than EB-treated rats that did not receive OT.
      Finally, OT antagonist administered to EB-treated rats reversed the effect of EB
      on food intake, suggesting that estrogen effects to decrease food intake may
      involve the oxytocinergic pathway.

PMID- 30118730
TI  - Keratinocyte Expression of A20/TNFAIP3 Controls Skin Inflammation Associated with
      Atopic Dermatitis and Psoriasis.
AB  - Keratinocytes are key players in chronic inflammatory skin diseases. A20
      regulates NF-kappaB-dependent expression of proinflammatory genes and cell death,
      but the impact of its expression in keratinocytes on systemic inflammation and
      skin disorders has not been determined. Comparative transcriptomic analysis of
      microdissected epidermis showed that A20 is down-regulated in involved epidermis,
      but not in dermis, of psoriasis and atopic dermatitis patients, suggesting that
      loss of A20 expression in keratinocytes increases the vulnerability for
      psoriasis/atopic dermatitis induction. We have previously shown that epidermis
      specific A20 knockout mice (A20EKO) develop mild epidermal hyperplasia but no
      macroscopic skin inflammation. We now show that various cytokines and chemokines
      are up-regulated in A20EKO mouse skin. A20EKO mice also display systemic
      proinflammatory changes, even in the absence of skin immune cell infiltration,
      and an exacerbated disease severity upon induction of experimental psoriasis,
      atopic dermatitis, or skin barrier disruption. Keratinocytes showed increased
      proinflammatory gene expression in the absence of A20 in unstimulated and IL-17A
      stimulated conditions, in part resulting from uncontrolled MyD88-dependent
      signaling. Our findings indicate that absence of A20 in keratinocytes leads to
      systemic inflammation at homeostatic conditions and is sufficient to exacerbate
      inflammatory skin disorders associated with different immune profiles by
      increasing cytokine and chemokine expression.

PMID- 30118731
TI  - Salts of Mefenamic Acid With Amines: Structure, Thermal Stability, Desolvation,
      and Solubility.
AB  - Salt formation has been known to improve some physicochemical properties of
      active pharmaceutical ingredients particularly solubility. In this study,
      mefenamic acid (MA) formed salts with ethylenediamine (EDM), triethylamine (TA),
      1-methylpiperazine (MP), and morpholine (MOP). In the salt structures studied,
      the proton of the carboxylic acid group of the MA molecule was transferred to a
      nitrogen atom of the amine. Both crystal structures of the ethylenediammonium and
      morpholinium salts were solved successfully by single-crystal X-ray diffraction
      in the space group PI. The triethylammonium and the 1-methylpiperazinium salts
      solved in Pbca and P21/c, respectively. The thermal behavior of the salts was
      investigated, and the desolvated powders were analyzed using powder X-ray
      diffraction. Grinding and slurry experiments were also investigated as alternate
      methods for preparation of the salts. The desolvation experiments yielded
      interesting results with the desolvation of (MA-)(MP+) resulting in MA form I,
      desolvation of (MA-)(TA+) gave mixtures of MA form I and MA form II, whereas
      desolvation of (MA-)(MOP+) gave MA form II. The solubility trend in water was
      determined as (MA-)(MP+) > (MA-)(TA+) > (MA-)(MOP+) > (MA-)(EDM+), with (MA
      )(MP+) the most-soluble and (MA-)(EDM+) the least-soluble salt.

PMID- 30118732
TI  - Evaluation of antiviral effects of novel NS5A inhibitors in hepatitis C virus
      cell culture system with full-genome infectious clones.
AB  - Nonstructural protein 5A (NS5A) inhibitors of hepatitis C virus (HCV) are known
      to have potent anti-viral effects; however, these inhibitors have limited
      activities on strains with resistant-associated substitutions or non-genotype 1
      strains. To overcome these shortcomings, novel NS5A inhibitors have been
      developed and approved for clinical application. The aim of this study was to
      evaluate the anti-viral effect of novel NS5A inhibitors (derivatives of
      odalasvir) on HCV genotype 2 strains in a cell culture system. Chimeric JFH-1
      viruses replaced with NS5A of genotypes 1 and 2 were utilized to assess the
      genotype-specific potencies of NS5A inhibitors. We also examined full-genome
      infectious clones of JFH-1, J6cc, and J8cc to confirm the effects of NS5A
      inhibitors on genotype 2 strains. All chimeric viruses were capable of
      replication at similar levels in cell culture. We examined the anti-viral effects
      of derivatives of the novel NS5A inhibitor and compared with the first-generation
      NS5A inhibitor, daclatasvir (DCV). These compounds inhibited replication of
      chimeric JFH-1 viruses with NS5A of genotypes 1 and 2 at low concentrations in
      comparison with DCV. The EC50 values of J6cc and J8cc to these compounds were
      more than 100-fold lower than that of DCV. By long-term culture in the presence
      of these compounds, we obtained highly resistant variants and identified the
      responsible substitutions. In conclusion, novel NS5A inhibitors displayed
      improved potency against HCV genotype 2 strains compared with DCV. However, the
      activity of these compounds was impaired by emerging resistance-associated
      substitutions.

PMID- 30118733
TI  - Behavioural sensitization to alcohol: Bridging the gap between preclinical
      research and human models.
AB  - Alcohol use disorder (AUD) is an increasingly prevalent disorder that contributes
      significantly to the global burden of disease. According to the incentive
      sensitization theory (IST) of addiction, repeated alcohol exposure produces
      persistent neuroadaptations that promote the craving, relapse, and drug-taking
      characteristic of addiction. Critical to the IST model is the prediction that
      stimulant or hedonic drug effects become more pronounced with repeated exposure
      (i.e., sensitization). While there is an extensive body of preclinical alcohol
      sensitization research, there have been few studies examining this aspect of the
      incentive sensitization model in human alcohol research. In particular,
      developmental studies assessing sensitization over time in humans are lacking,
      due largely to ethical considerations precluding alcohol administration in
      alcohol-naive individuals, and the lack of a reliable protocol for the
      prospective measurement of sensitization. The lack of translation between
      preclinical and human models of alcohol sensitization presents a significant
      barrier to further understanding the relevance of IST to the development and
      progression of AUD. The present review discusses how the gap between preclinical
      and clinical alcohol sensitization research can be bridged and how animal studies
      can inform human alcohol sensitization research.

PMID- 30118734
TI  - Extracellular dsRNA induces a type I interferon response mediated via class A
      scavenger receptors in a novel Chinook salmon derived spleen cell line.
AB  - Despite increased global interest in Chinook salmon aquaculture, little is known
      of their viral immune defenses. This study describes the establishment and
      characterization of a continuous cell line derived from Chinook salmon spleen,
      CHSS, and its use in innate immune studies. Optimal growth was seen at 14-18 
      degrees C when grown in Leibovitz's L-15 media with 20% fetal bovine serum. DNA
      analyses confirmed that CHSS was Chinook salmon and genetically different from
      the only other available Chinook salmon cell line, CHSE-214. Unlike CHSE-214,
      CHSS could bind extracellular dsRNA, resulting in the rapid and robust expression
      of antiviral genes. Receptor/ligand blocking assays confirmed that class A
      scavenger receptors (SR-A) facilitated dsRNA binding and subsequent gene
      expression. Although both cell lines expressed three SR-A genes: SCARA3, SCARA4,
      and SCARA5, only CHSS appeared to have functional cell-surface SR-As for dsRNA.
      Collectively, CHSS is an excellent cell model to study dsRNA-mediated innate
      immunity in Chinook salmon.

PMID- 30118735
TI  - Cation-dependent mannose-6-phosphate receptor functions as a pattern recognition
      receptor in anti-bacterial immunity of Marsupenaeus japonicus.
AB  - The cation-dependent mannose-6-phosphate receptor (CD-MPR) is a member of the P
      type lectin family. As a type I transmembrane glycoprotein, it functions in the
      delivery of newly synthesized acid hydrolases from the trans-Golgi network to
      endosomes for their subsequent transfer to the lysosome by binding the mannose-6
      phosphate receptor-recognition moieties in the hydrolases. However, the functions
      of CD-MPR in immune responses are seldom reported. In the present study, we
      identified a CD-MPR-like molecule in Marsupenaeus japonicus and designed it as
      MjCD-MPR. It was significantly upregulated after challenge with Vibrio
      anguillarum at the mRNA and protein levels. Knockdown of MjCD-MPR resulted in a
      significant increase in the amount of V. anguillarum in the hemolymph of shrimp,
      which suggested that MjCD-MPR plays a role in shrimp antibacterial defense. The
      recombinant extracytoplasmic region of MjCD-MPR could bind gram-positive and gram
      negative bacteria by interaction with peptidoglycan, lipopolysaccharide, and
      lipoteichoic acid. MjCD-MPR showed no direct bacteriostatic or bacteriocidal
      activity. Knockdown of MjCD-MPR decreased the expression levels of several
      antimicrobial peptides (Alf-C1, Alf-E1, Crustin I-2, and Crustin I-3), suggesting
      that MjCD-MPR promotes the expression of antimicrobial peptides in shrimp. In
      summary, working as a pattern recognition receptor, MjCD-MPR recognizes invading
      bacteria and triggers the expression of AMPs against bacterial infection in
      shrimp.

PMID- 30118736
TI  - Primary peritoneal Epithelioid mesothelioma of clear cell type with a novel VHL
      gene mutation: a case report.
AB  - Clear cell variant of epithelioid mesothelioma is an extremely rare tumor with
      only isolated cases reported so far in the peritoneum. Here, we report a case of
      peritoneal epithelioid mesothelioma, clear cell variant, in a 63-year-old female
      patient with a novel VHL gene mutation and an unusual indolent clinical course.
      The patient, who has no clinical history of asbestos exposure, presented with a
      27.2 cm upper abdominal mass and a 5.5 cm liver lesion. Retrospective review of
      the patient's abdominal CT scan 4 years ago showed two small abdominal lesions
      that were felt clinically to represent hemangiomas. These were retrospectively
      considered to have grown in size and represented the current abdominal mass. Both
      masses were subsequently biopsied and showed a proliferation of monomorphic
      epithelioid cells with distinct cell membranes, fine chromatin and clear to
      finely vacuolated pale eosinophilic cytoplasm arranged in nests and solid sheets.
      Immunohistochemical staining confirmed it to be malignant mesothelioma. Clear
      cell variant of peritoneal epithelioid mesothelioma should always be considered
      in patients with an abdominal or pelvic mass with clear cell features. Given the
      rarity of such entity, its clinical course and prognosis remains unclear.

PMID- 30118737
TI  - Circuit mechanisms and computational models of REM sleep.
AB  - Rapid eye movement (REM) sleep or paradoxical sleep is an elusive behavioral
      state. Since its discovery in the 1950s, our knowledge of the neuroanatomy,
      neurotransmitters and neuropeptides underlying REM sleep regulation has
      continually evolved in parallel with the development of novel technologies.
      Although the pons was initially discovered to be responsible for REM sleep, it
      has since been revealed that many components in the hypothalamus, midbrain, pons,
      and medulla also contribute to REM sleep. In this review, we first provide an up
      to-date overview of REM sleep-regulating circuits in the brainstem and
      hypothalamus by summarizing experimental evidence from neuroanatomical,
      neurophysiological and gain- and loss-of-function studies. Second, because
      quantitative approaches are essential for understanding the complexity of REM
      sleep-regulating circuits and because mathematical models have provided valuable
      insights into the dynamics underlying REM sleep genesis and maintenance, we
      summarize computational studies of the sleep-wake cycle, with an emphasis on REM
      sleep regulation. Finally, we discuss outstanding issues for future studies.

PMID- 30118738
TI  - Regulation of neuronal/axonal degeneration by ZNRF1 ubiquitin ligase.
AB  - ZNRF1 is an E3 ubiquitin ligase constitutively expressed in almost all neurons in
      the central and peripheral nervous systems during development and in adulthood.
      From this expression profile, the role of ZNRF1 is assumed to be common to many
      different types of neurons. We have analyzed the roles of ZNRF1-dependent
      degradation of target proteins in neurons. In mature neurons, ZNRF1 is activated
      in response to different types of stress that cause neuronal/axonal degeneration,
      and degrade AKT to activate GSK3B. Here we summarize the subcellular signaling
      events downstream of GSK3B activation, and their roles in the progression of
      neuronal/axonal degeneration.

PMID- 30118739
TI  - Pregabalin and lacosamide ameliorate paclitaxel-induced peripheral neuropathy via
      inhibition of JAK/STAT signaling pathway and Notch-1 receptor.
AB  - Anticonvulsant drugs such as pregabalin (PGB) and lacosamide (LCM), exhibit
      potent analgesic effects in diabetic neuropathy; however, their possible
      role/mechanisms in paclitaxel (PTX)-induced peripheral neuropathy have not been
      elucidated, which is the aim of the present study. Neuropathic pain was induced
      in rats by injecting PTX (2 mg/kg, i. p) on days 0, 2, 4 and 6. Forty eight hours
      after the last dose of PTX, rats were treated orally with 30 mg/kg/day of either
      PGB or LCM for 21 days. Both therapies improved thermal hyperalgesia and cold
      allodynia induced by PTX. Interestingly, LCM therapy showed no motor impairment
      that was observed upon using PGB, as demonstrated using rotarod test. Treatment
      with PGB or LCM restored the sciatic nerve content of the depleted total
      antioxidant capacity (TAC) and nerve growth factor (NGF), and lessened the
      elevated contents of nuclear factor kappa B p65 (NF-kB p65), tumor necrosis
      factor-alpha (TNF-alpha), and active caspase-3. On the molecular level, the drugs
      reduced the protein expression of Notch1 receptor, phosphorylated p38 mitogen
      activated protein kinase (p-p38-MAPK), and the trajectory interleukin
      6/phosphorylated janus kinase 2/phosphorylated signal transducer and activator of
      transcription 3 (IL-6/p-JAK2/p-STAT3). Therefore, the current study demonstrated
      a pivotal role for LCM in the management of PTX-induced peripheral neuropathy
      similar to PGB, but without motor adverse effects via the inhibition of oxidative
      stress, inflammation and apoptosis, as well as IL-6/JAK/STAT pathway and Notch1
      receptor over-expression.

PMID- 30118740
TI  - Recovery after spinal cord injury by modulation of the proteoglycan receptor
      PTPsigma.
AB  - SCI is followed by dramatic upregulation of chondroitin sulfate proteoglycans
      (CSPGs) which limit axonal regeneration, oligodendrocyte replacement and
      remyelination. The recent discovery of the specific CSPGs signaling receptor
      protein tyrosine phosphatase sigma (RPTPsigma) provided an opportunity to refine
      the therapeutic approach to overcome CSPGs inhibitory actions. In previously
      published work, subcutaneous (s.c.) delivery of 44 MUg/day of a peptide mimetic
      of PTPsigma called intracellular sigma peptide (ISP), which binds to PTPsigma and
      blocks CSPG-mediated inhibition, facilitated recovery after contusive SCI. Since
      this result could be of great interest for clinical trials, we independently
      repeated this study, but modified the method of injury as well as peptide
      application and the dosage. Following SCI at the Th10-segment, 40 rats were
      distributed in 3 groups. Animals in group 1 (20 rats) were subjected to SCI, but
      received no treatment. Rats in group 2 were treated with intraperitoneal (i.p.)
      injections of 44 MUg/day ISP (SCI + ISP44) and animals of group 3 with s.c.
      injections of 500 MUg/day ISP (SCI + ISP500) for 7 weeks after lesioning.
      Recovery was analyzed at 1, 3, 6, 9 and 12 weeks after SCI by determining (i) BBB
      score, (ii) foot-stepping angle, (iii) rump-height index, (iv) number of correct
      ladder steps, (v) bladder score and (vi) sensitivity (withdrawal latency after
      thermal stimulus). Finally, we determined the amount of serotonergic fibers in
      the preserved neural tissue bridges (PNTB) around the lesion site. Our results
      show that, systemic therapy with ISP improved locomotor, sensory and vegetative
      recovery which correlated with more spared serotonergic fibers in PNTB.

PMID- 30118741
TI  - Potential Overestimation of Racial Disparities in Response to the 8-Week
      Ledipasvir/Sofosbuvir Regimen for Hepatitis C Virus Genotype 1 Infection.

PMID- 30118742
TI  - What Is the True Relationship Between Spontaneous Portosystemic Shunts and
      Portopulmonary Hypertension in Cirrhotic Patients?

PMID- 30118743
TI  - Multiple Bidirectionality Brain-Gut Interactions in Patients With Inflammatory
      Bowel Disease.

PMID- 30118744
TI  - Portosystemic Shunt Embolization and Recurrent Ascites: A Single-Center Case
      Series.

PMID- 30118746
TI  - Philip J. Bushnell, Ph.D. (1947-2018).

PMID- 30118745
TI  - Reserve Stem Cells in Intestinal Homeostasis and Injury.
AB  - Renewal of the intestinal epithelium occurs approximately every week and requires
      a careful balance between cell proliferation and differentiation to maintain
      proper lineage ratios and support absorptive, secretory, and barrier functions.
      We review models used to study the mechanisms by which intestinal stem cells
      (ISCs) fuel the rapid turnover of the epithelium during homeostasis and might
      support epithelial regeneration after injury. In anatomically defined zones of
      the crypt stem cell niche, phenotypically distinct active and reserve ISC
      populations are believed to support homeostatic epithelial renewal and injury
      induced regeneration, respectively. However, other cell types previously thought
      to be committed to differentiated states might also have ISC activity and
      participate in regeneration. Efforts are underway to reconcile the proposed
      relatively strict hierarchical relationships between reserve and active ISC pools
      and their differentiated progeny; findings from models provide evidence for
      phenotypic plasticity that is common among many if not all crypt-resident
      intestinal epithelial cells. We discuss the challenges to consensus on ISC
      nomenclature, technical considerations, and limitations inherent to methodologies
      used to define reserve ISCs, and the need for standardized metrics to quantify
      and compare the relative contributions of different epithelial cell types to
      homeostatic turnover and post-injury regeneration. Increasing our understanding
      of the high-resolution genetic and epigenetic mechanisms that regulate reserve
      ISC function and cell plasticity will help refine these models and could affect
      approaches to promote tissue regeneration after intestinal injury.

PMID- 30118747
TI  - A host-feeding wasp shares several features of nitrogen management with blood
      feeding mosquitoes.
AB  - Adult feeding on hosts is common among parasitic wasps. The ingested host fluid
      is rich in nutrients, especially proteins. A study on Eupelmus vuilleti
      (Hymenoptera: Eupelmidae), a host-feeding parasitoid of larvae of Callosobruchus
      maculatus (F.) (Coleoptera: Bruchidae), showed that the carbohydrates (maybe
      lipids) but not proteins, gained from host feeding accounted for the increased
      egg production. Thus, host protein is probably utilized for general adult
      metabolism, allowing conservation of carbohydrate and/or lipid resources for
      direct allocation to oocytes. In that case, there should be increased N excretion
      by female parasitoids. To test this, we studied the dynamics of excretion in E.
      vuilleti with and without host exposure. The aim of this work was threefold: (i)
      to identify the major N-containing compounds in adult excreta, (ii) to assess
      whether protein consumption during host feeding increased the amount of N
      excreted, and (iii), if so, to compare the increase in N excreted with the amount
      taken in during a single host feeding. We found that uric acid is the predominant
      N-containing metabolite in excreta, although small quantities of urea and traces
      of allantoin were also found. A calculation of the N budget showed that the extra
      quantity of N excreted following a host meal corresponds to the quantity
      ingested, confirming that host-feeding in this species offers little or no net
      quantitative benefit in N allocation to oocytes, although the allocation of
      specific amino acids from host feeding cannot be discounted. Interestingly, host
      feeding in parasitoids appears analogous to vertebrate blood-feeding in
      mosquitoes, both in terms of the N-containing compounds excreted and the offset
      of acquired N to metabolism, rather than to oocytes. Further comparative and
      detailed investigations of N excretion in insects living on other N-rich fluids
      might establish further metabolic commonalities.

PMID- 30118748
TI  - Diabetes education and health insurance: How they affect the quality of care
      provided to people with type 1 diabetes in Latin America. Data from the
      International Diabetes Mellitus Practices Study (IDMPS).
AB  - AIMS: This study aimed to evaluate the impact of diabetes education and access to
      healthcare coverage on disease management and outcomes in Latin America. METHODS:
      Data were obtained from a sub-analysis of 2693 patients with type 1 diabetes
      mellitus recruited from 9 Latin American countries as part of the International
      Diabetes Mellitus Practices Study (IDMPS), a multinational, observational survey
      of diabetes treatment in developing regions. RESULTS: Results from the Latin
      American cohort show that only 25% of participants met HbA1c target value (< 7%
      [53 mmol/mol]). Attainment of this target was significantly higher among
      participants who had received diabetes education than those who hadn't (28% vs.
      19%, p < 0.001), and among those who practiced self-management (27% vs. 21% no
      self-management, p = 0.001). Multivariate analysis showed that participants who
      had received diabetes education were more likely to manage their diabetes
      (OR:1.65 [95% CI: 1.24, 2.19]; p = 0.001), and to attain HbA1c target values
      (OR:1.48 [95% CI: 1.14, 1.93]; p = 0.003). CONCLUSIONS: Given the association
      between uncontrolled diabetes and long-term complications, health authorities and
      care providers should increase efforts to ensure widespread healthcare coverage
      and access to self-management education to reduce the socioeconomic and
      humanistic burden of type 1 diabetes.

PMID- 30118749
TI  - Deltamethrin Intranasal administration induces memory, emotional and tyrosine
      hydroxylase immunoreactivity alterations in rats.
AB  - Parkinson's disease (PD) is a neurodegenerative disease related to the
      dopaminergic system. The etiology is not fully understood, but it is known that
      PD is a multifactorial disease that involves genetic and environmental factors,
      including pesticides. One of these, Deltamethrin (DM), has been widely used for
      vector control in crops, farming, veterinary medicine and domestic pest control.
      The purpose of the present study was to investigate the effect of DM repeated
      administration on motor, cognitive and emotional behavior and dopaminergic
      parameters. Male Wistar rats received 3 intranasal (i.n.) injections of 100 MUL
      (50 MUL/nostril) of DM 0.5 MUg/MUl or Vehicle (saline solution 0.9%), one
      injection per week. We observed that DM caused memory (novel object recognition
      task) and emotion (contextual conditioned fear) alterations accompanied by
      reduction of TH immunoreactivity in the substantia nigra pars compacta (SNpc) and
      ventral tegmental area (VTA), and increase of TH immunoreactivity in the dorsal
      striatum. Motor alterations (catalepsy and open field task) were not observed
      throughout treatment. These findings suggest a possible early disruption of the
      dopaminergic pathway caused by repeated DM exposure, similar to that observed in
      early stages of PD.

PMID- 30118750
TI  - Osthole alleviated diabetic neuropathic pain mediated by the P2X4 receptor in
      dorsal root ganglia.
AB  - Diabetes mellitus (DM) is considered the primary cause of neuropathic pain.
      Osthole (7-methoxy-8[3-methylpent 2-enyl]coumarin) is a component extracted from
      Cnidium monnieri (L.) cusson plant seeds and has anti-inflammatory and anti
      oxidative properties. The aim of the present study was to investigate the effects
      of osthole on diabetic neuropathic pain (DNP) involving the P2X4 receptor on
      satellite glial cells (SGCs) in the dorsal root ganglia (DRG) of type 2 diabetic
      rats. These data showed that the mechanical withdrawal threshold (MWT) and
      thermal withdrawal latency (TWL) in DM rats were lower than those in control
      rats. MWT and TWL in DM rats treated with osthole were higher compared with those
      in untreated DM rats. The expression levels of P2X4 mRNA and protein in the DRG
      of DM rats were higher compared with those in the control rats, while those in DM
      rats treated with osthole were significantly lower compared with those in the
      untreated DM rats. Osthole treatment decreased the co-expression levels of P2X4
      and glial fibrillary acidic protein (GFAP) and reduced the up-regulated
      expression of interleukin-1 beta (IL-1beta), tumour necrosis factor-alpha (TNF
      alpha), brain-derived neurotrophic factor (BDNF) and phosphorylated-p38MAPK and
      enhanced the down-regulation of IL-10 in DM rats. Thus, osthole treatment may act
      on the P2X4 receptor to alleviate the mechanical and thermal hyperalgesia in DM
      rats.

PMID- 30118751
TI  - Aberrant Amygdala-dependent Fear Memory in Corticosterone-treated Mice.
AB  - Anxiety disorder is a major psychiatric disorder characterized by fear, worry,
      and excessive rumination. However, the molecular mechanisms underlying neural
      plasticity and anxiety remain unclear. Here, we utilized a mouse model of anxiety
      like behaviors induced by the chronic administration of corticosterone (CORT) to
      determine the exact mechanism of each region of the fear circuits in the anxiety
      disorders. Chronic CORT-treated mice showed a significant increase in anxiety
      related behaviors as assessed by the elevated plus maze, light-dark, open-field,
      and marble-burying tasks. In addition, chronic CORT-treated mice exhibited
      abnormal amygdala-dependent tone-induced fear memory but normal hippocampus
      dependent contextual memory. Consistent with amygdala hyperactivation, chronic
      CORT-treated mice showed significantly increased numbers of c-Fos-positive cells
      in the basolateral amygdala (BLA) after tone stimulation. Long-term potentiation
      (LTP) was markedly enhanced in the BLA of chronic CORT-treated mice compared to
      that of vehicle-treated mice. Immunoblot analyses revealed that
      autophosphorylation of Ca2+/calmodulin-dependent protein kinase (CaMK) IIalpha at
      threonine 286 and phosphorylation of cyclic-adenosine-monophosphate response
      element-binding protein (CREB) at serine 133 were markedly increased in the BLA
      of chronic CORT-treated mice after tone stimulation. The protein and mRNA levels
      of brain-derived neurotrophic factor (BDNF) also significantly increased. Our
      findings suggest that increased CaMKII activity and synaptic plasticity in the
      BLA likely account for the aberrant amygdala-dependent fear memory in chronic
      CORT-treated mice.

PMID- 30118752
TI  - Biophysical virus particle specific characterization to sharpen the definition of
      virus stability.
AB  - Vaccine thermostability is key to successful global immunization programs as it
      may have a significant impact on the continuous cold-chain maintenance logistics,
      as well as affect vaccine potency. Modern biological and biophysical techniques
      were combined to in-depth characterize the thermostability of a formulated rabies
      virus (RABV) in terms of antigenic and genomic titer, virus particle count and
      aggregation state. Tunable resistive pulse sensing (TRPS) and nanoparticle
      tracking analysis (NTA) were used to count virus particles while simultaneously
      determining their size distribution. RABV antigenicity was assessed by NTA using
      a monoclonal antibody that recognize a rabies glycoprotein (G protein)
      conformational epitope, enabling to specifically count antigenic rabies viruses.
      Agreement between antigenicity results from NTA and conventional method, as
      ELISA, was demonstrated. Additionally, NTA and ELISA showed mirrored loss of RABV
      antigenicity during forced degradation studies performed between 5  degrees C and
      45  degrees C temperature exposure for one month. Concomitant with decreased
      antigenicity, emergence of RABV particle populations larger than those expected
      for rabies family viruses was observed, suggesting RABV aggregation induced by
      thermal stress. Finally, using a kinetic-based modeling approach to explore
      forced degradation antigenicity data (NTA, ELISA), a two-step model accurately
      describing antigenicity loss was identified. This model predicted a RABV shelf
      life of more than 3 years at 5  degrees C; significant loss of antigenicity was
      predicted for samples maintained several months at ambient temperature. This
      thorough characterization of RABV forced degradation study originally provided a
      time-temperature mapping of RABV stability.

PMID- 30118753
TI  - Correlation of antimicrobial effects of phenoxyethanol with its free
      concentration in the water phase of o/w-emulsion gels.
AB  - Antimicrobial testing is a time consuming and cost-intensive but essential method
      for evaluation of newly developed pharmaceutical formulations for topical use. In
      this study the correlation between free preservative concentration in emulsion
      gels measured by equilibrium dialysis and the successful preservative
      effectiveness testing for Pseudomonas aeruginosa, Staphylococcus aureus, Candida
      albicans and Aspergillus brasiliensis (analyzed according to Ph. Eur. and USP)
      was investigated. The higher the lipophilicity of the oil phase and the lower the
      content of the aqueous phase with regard to dissolved ingredients the more
      preferably distributed is phenoxyethanol to the water phase and, consequently,
      the higher was the efficacy against the microbes. Increased emulsifier
      concentrations reduced the free amount of the preservative due to micellar
      interactions. Aspergillus brasiliensis was the most resistant and Staphylococcus
      aureus the most sensitive germ towards phenoxyethanol in o/w-emulsion gels.

PMID- 30118754
TI  - Reproductive status affects the expression of prolactin receptor mRNA in the
      brain of female Damaraland mole-rats.
AB  - The eusocial Damaraland mole-rat (Fukomys damarensis) represents an extreme
      example of reproductive skew, in that reproduction is completely blocked in
      female subordinate group members. It is thought that in these animals normal GnRH
      secretion from the hypothalamus is disrupted. Prolactin, a peptide hormone
      secreted from the anterior pituitary gland, has been implicated in a wide variety
      of functions. Well documented in rodents is its role in mediating lactational
      infertility. Elevated circulating prolactin levels, such as during lactation, are
      associated with reduced GnRH release into the portal blood and with a reduction
      in the frequency and amplitude of LH pulses. The present study aimed at
      investigating whether such a mechanism could act in reproductively suppressed
      female Damaraland mole-rats. By means of in situ hybridisation we studied the
      distribution and gene expression of the prolactin receptor (Prlr) in wild-caught
      female Damaraland mole-rats with different reproductive status. Substantial Prlr
      expression was found in several brain regions, with highest levels in the choroid
      plexus and moderate expression in the preoptic and tuberal hypothalamus. While in
      reproductive and non-reproductive females plasma prolactin levels were very low
      and not significantly different, quantification of the Prlr hybridisation signal
      revealed significant differences in relation to reproductive status.
      Reproductively suppressed females had increased expression of Prlr in the choroid
      plexus and in the arcuate nucleus (ARC) when compared to reproductive females.
      This suggests higher local prolactin levels in the brain of suppressed females.
      Together with previous findings, it could indicate that prolactin inhibits ARC
      kisspeptin neurons, which then would lead to reduced activation of GnRH neurons
      in such females.

PMID- 30118755
TI  - Genetics of stroke recovery: BDNF val66met polymorphism in stroke recovery and
      its interaction with aging.
AB  - Stroke leads to long term sensory, motor and cognitive impairments. Most patients
      experience some degree of spontaneous recovery which is mostly incomplete and
      varying greatly among individuals. The variation in recovery outcomes has been
      attributed to numerous factors including lesion size, corticospinal tract
      integrity, age, gender and race. It is well accepted that genetics play a crucial
      role in stroke incidence and accumulating evidence suggests that it is also a
      significant determinant in recovery. Among the number of genes and variations
      implicated in stroke recovery the val66met single nucleotide polymorphism (SNP)
      in the BDNF gene influences post-stroke plasticity in the most significant ways.
      Val66met is the most well characterized BDNF SNP and is common (40-50 % in Asian
      and 25-32% in Caucasian populations) in humans. It reduces activity-dependent
      BDNF release, dampens cortical plasticity and is implicated in numerous diseases.
      Earlier studies on the effects of val66met on stroke outcome and recovery
      presented primarily a maladaptive role. Novel findings however indicate a much
      more intricate interaction between val66met and stroke recovery which appears to
      be influenced by lesion location, post-stroke stage and age. This review will
      focus on the role of BDNF and val66met SNP in relation to stroke recovery and try
      to identify potential pathophysiologic mechanisms involved. The effects of age on
      val66met associated alterations in plasticity and potential consequences in terms
      of stroke are also discussed.

PMID- 30118756
TI  - How choice influences risk processing: An ERP study.
AB  - The current study examined how the experience of choice by which individuals
      exercise control modulates risk processing during the anticipatory phase as
      indexed by the stimulus-preceding negativity (SPN), and the consummatory phase as
      indexed by the feedback-related negativity (FRN) and feedback P3 (fb-P3). Twenty
      four participants performed a simple gambling task during which they could win or
      lose either a small (a low-risk condition) or a large (a high-risk condition)
      amount of points by either choosing freely between two doors (a choice condition)
      or accepting a computer-selected door (a no-choice condition) while their EEG was
      recorded. As expected, participants rated the high-risk condition as more risky
      than the low-risk condition and reported higher feelings of control for the
      choice versus no-choice condition. Regardless of the involvement of choice, risk
      processing in this task was associated with greater fb-P3 amplitudes. However,
      during the choice condition, risk processing was associated with a more negative
      SPN during the anticipatory phase and a more positive FRN during the consummatory
      phase, which was absent (the SPN) or reduced (the FRN) in the no-choice
      condition. These findings suggest that the modulation of risk processing by
      choice occurs during both the anticipatory phase and the consummatory phase,
      which may be driven by motivation salience imposed by control.

PMID- 30118757
TI  - Effects of acute stress provocation on cortisol levels, zonulin and inflammatory
      markers in low- and high-stressed men.
AB  - The virtual version of the Trier Social Stress Test (V-TSST) is an effective and
      standardized tool for social stress induction. This study aimed to examine gut
      permeability and physiological and inflammatory markers of reactivity to acute
      psychosocial stress. Forty young men were classified as high-stressed (HIGHS) or
      low-stressed (LOWS) according to the Shirom-Melamed Burnout Questionnaire.
      Cardiovascular reactivity and gut dysfunction were studied along with cortisol,
      zonulin and cytokines. Gut permeability was shown to be affected within one hour
      after the psychosocial stress induction, and shown to be dependent on age.
      Interleukin-6 increased with time, most pronounced at the end of the one-hour
      recovery after V-TSST, and was positively correlated to age. HIGHS experienced
      more abdominal dysfunction compared to LOWS. In conclusion, this study is the
      first to show fluctuations in gut permeability after psychosocial stress
      induction. This was partly associated with changes in inflammatory markers.

PMID- 30118758
TI  - NephroTalk: Evaluation of a Palliative Care Communication Curriculum for
      Nephrology Fellows.
AB  - CONTEXT: Nephrologists care for a medically complex population that faces
      difficult decisions around treatment options and end-of-life care. Yet
      communication training within nephrology fellowship is rare. Prior work suggests
      that communication training in nephrology can improve perceived preparedness to
      engage in difficult conversations; however, it is unclear if this training
      results in improved clinical skills. OBJECTIVES: The primary aim was to evaluate
      the efficacy of a three-day curriculum for nephrology fellows (NephroTalk) to
      improve communication skill acquisition for delivering serious news. We also
      measured self-reported preparedness for three additional communication tasks
      taught, including goals of care and transitions at end of life. METHODS: Thirty
      three first- and second-year fellows from seven academic nephrology programs
      participated in NephroTalk from 2015 to 2016. Pretraining and post-training
      encounters to deliver bad news with standardized patients were audiorecorded and
      evaluated using a modified communication checklist. Fellow experience and self
      reported improvement in communication tasks were measured using a five-point
      Likert scale. RESULTS: Skill use increased after training for seven of the nine
      skills measured (P < 0.01). The average number of skills gained after training
      was 3.6 +/- 1.8 skills. With increased communication proficiency, post-training
      encounters were significantly shorter than pretraining encounters (P = 0.03).
      Fellows reported improved preparedness to engage in all communication tasks
      taught in NephroTalk curriculum. CONCLUSION: Our findings support NephroTalk as
      an effective communication skills curriculum for nephrology trainees. Fellows
      increased their communication skills significantly in delivering bad news leading
      to more efficient encounters.

PMID- 30118759
TI  - Factor XII in coagulation, inflammation and beyond.
AB  - Factor XII (FXII) is a protease that is mainly produced in the liver and
      circulates in plasma as a single chain zymogen. Following contact with negatively
      charged surfaces, FXII is converted into the two-chain active form, FXIIa. FXIIa
      initiates the intrinsic blood coagulation pathway via activation of factor XI.
      Furthermore, it converts plasma prekallikrein to kallikrein (PK), which
      reciprocally activates FXII and liberates bradykinin from high molecular weight
      kininogen. In addition, FXIIa initiates fibrinolysis via PK-mediated urokinase
      activation and activates the classical complement pathway. Even though the main
      function of FXII seems to relate to the activation of the intrinsic coagulation
      pathway and the kallikrein-kinin system, a growing body of evidence suggests that
      FXII may also directly regulate cellular responses. In this regard, it has been
      found that FXII/FXIIa induces the expression of inflammatory mediators, promotes
      cell proliferation, and enhances the migration of neutrophils and lung
      fibroblasts. In addition, it has been reported that genetic ablation of FXII
      protects against neuroinflammation, reduces the formation of atherosclerotic
      lesions in Apoe-/- mice, improves wound healing, and inhibits postnatal
      angiogenesis. Although the aforementioned effects can be partially explained by
      the downstream products of FXII activation, the ability of FXII/FXIIa to directly
      regulate cellular responses has recently emerged as an alternative hypothesis.
      These direct cellular reactions to FXII/FXIIa will be discussed in the review.

PMID- 30118760
TI  - FOXO3a-dependent up-regulation of Mxi1-0 promotes hypoxia-induced apoptosis in
      endothelial cells.
AB  - Endothelial cell apoptosis induced by hypoxia is implicated in the pathogenesis
      of vascular diseases. However, the underlying mechanism is not clearly
      elucidated. In this study, we found that hypoxia increased Mxi1-0 expression, and
      the Mxi1-0 siRNA could inhibit caspase-8 activation and apoptosis in HUVECs
      induced by hypoxia. In addition, hypoxia induced FOXO3 activation, while Mxi1-0
      expression and apoptosis were inhibited by transfection with FOXO3 siRNA. Using
      ChIP assay, we confirmed that FOXO3a binds to the Mxi1-0 promoter region.
      Furthermore, hypoxia treatment leads to remarkable production of reactive oxygen
      species (ROS), while ROS scavenger N-acetyl-L-cysteine (NAC) inhibits hypoxia
      induced ROS production, apoptosis and FOXO3a-mediated Mxi1-0 up-regulation.
      Finally, we found that the HIF-1alpha siRNA inhibited hypoxia-induced HIF-1alpha
      expression and ROS production, as well as FOXO3a/Mxi1-0 activation and apoptosis
      in HUVECs. Taken together, this study identifies a HIF-1alpha/FOXO3a/Mxi1
      0/caspase-8 signaling pathway in hypoxia-induced endothelial cell apoptosis.
      These data also indicate that HIF-1alpha-dependent ROS production is required for
      FOXO3a-mediated Mxi1-0 up-regulation and apoptosis in hypoxic endothelial cells.

PMID- 30118761
TI  - Accuracy of quick sequential organ failure assessment score to predict mortality
      in hospitalized patients with suspected infection in an HIV/AIDS reference centre
      in Rio de Janeiro, Brazil.
AB  - OBJECTIVES: To compare the discriminatory capacity of the quick sequential organ
      failure assessment (qSOFA) vs. the systemic inflammatory response syndrome (SIRS)
      score for predicting 30-day mortality and intensive care unit (ICU) admission in
      patients with suspicion of infection at an HIV reference centre. METHODS: We
      performed a prospective cohort study including consecutive adult patients who had
      suspected infection and who were subsequently admitted to the medical ward.
      Variables related to qSOFA and SIRS were measured at admission. The performance
      (area under the receiver operating curve, AUROC) of qSOFA (score >=2) and SIRS
      (>=2 criteria) as a predictor of 30-day mortality and ICU admission was
      evaluated. RESULTS: One hundred seventy-three patients (mean +/- standard
      deviation age, 42.6 +/- 12.4 years) were included in the analysis; 107 (61.8%)
      were male, and 111 (64.2%) were HIV positive. Respiratory and gastrointestinal
      infections occurred in 49 (28.3%) and 23 (13.3%), respectively. The 30-day
      mortality rate was 9 (5.2%) of 173. The prognostic performance of qSOFA was
      similar compared to SIRS, with an AUROC of 0.68 (95% confidence interval, 0.55
      0.81) and 0.69 (95% confidence interval, 0.53-0.86) (p 0.96). Twenty patients
      (11%) were admitted to the ICU; qSOFA and SIRS had a similar discriminatory
      capacity for ICU admission (AUROC 0.63 (95% confidence interval, 0.51-0.75) and
      0.63 (95% confidence interval, 0.50-0.76)), respectively). CONCLUSIONS: We found
      a poor prognostic accuracy of the qSOFA to predict 30-day mortality in
      hospitalized patients suspected of infection in a setting with a high burden of
      HIV infection.

PMID- 30118762
TI  - Randomized controlled trials in CMI.

PMID- 30118763
TI  - Two flavonoid metabolites, 3,4-dihydroxyphenylacetic acid and 4-methylcatechol,
      relax arteries ex vivo and decrease blood pressure in vivo.
AB  - SCOPE: The flavonoid quercetin reduces arterial blood pressure in animals and
      humans but the mechanisms remains elusive. The aim of this study was to test the
      activity of flavonoid microbial metabolites, which can participate on the final
      vasorelaxant effect. METHODS AND RESULTS: Both ex vivo (isolated rat thoracic
      aorta and mesenteric artery) and in vivo (normotensive and spontaneously
      hypertensive rats) approaches were used in this study. 4-methylcatechol and 3,4
      dihydroxyphenylacetic acid (DHPA) had greater vasorelaxant effects on mesenteric
      artery than 3-(3-hydroxyphenyl)propionic acid, the previously reported metabolite
      with vasorelaxant effect. In vivo testing confirmed their blood pressure
      decreasing effect given both as bolus and slow infusion. Their mechanism at
      molecular level was different. CONCLUSIONS: This study is the first to show that
      flavonoid metabolites DHPA and 4-methylcatechol decrease arterial blood pressure
      and hence a mixture of microbial metabolites formed in the gastrointestinal tract
      may be responsible for or contribute to the effect of orally ingested quercetin.

PMID- 30118765
TI  - Clinical cases of VIM-producing Pseudomonas mendocina from two burned patients.

PMID- 30118764
TI  - Influence of dietary lipid levels on growth, nutrient utilization, tissue fatty
      acid composition and desaturase gene expression in silver barb (Puntius
      gonionotous) fingerlings.
AB  - Silver barb (Puntius gonionotus) is considered as a promising medium-sized carp
      species for freshwater aquaculture in Asia. This study in silver barb was carried
      out to evaluate the effects of increasing dietary levels of lipid on growth,
      nutrient utilization, whole-body composition, tissue fatty acid composition and
      Delta6 fatty acyl desaturase (Delta6 fad) gene expression. Fish (11.3 +/- 0.23 g
      of initial body weight) was fed for 60 days with five experimental diets: FO-0
      (control feed); FO-30; FO-60; FO-90 and FO-120 containing 0, 30, 60, 90 and 120 g
      fish oil kg-1 diet, respectively. Among the diets, the highest specific growth
      rate (SGR), protein efficiency ratio (PER) and whole-body lipid content, and the
      lowest feed conversion ratio (FCR) were recorded with FO-120 diet. The saturated
      fatty acids (SFA) level in the muscle was significantly (P < .05) increased with
      the enhanced FO supplementation, whereas monounsaturated fatty acids (MUFA) level
      decreased. Increased level of fish oil in the diet also enhanced the n-3 PUFA and
      n-3 LC-PUFA (long-chain polyunsaturated fatty acid) in the muscle and liver. The
      expression of Delta6 fad gene was downregulated, whereas the serum biochemical
      constituents were either remain unchanged or enhanced with increased FO
      supplementation in the diets of silver barb.

PMID- 30118766
TI  - Biodegradation of a monochlorotriazine dye, cibacron brilliant red 3B-A in solid
      state fermentation by wood-rot fungal consortium, Daldinia concentrica and
      Xylaria polymorpha: Co-biomass decolorization of cibacron brilliant red 3B-A dye.
AB  - Efficient decolorization of cibracron brilliant red 3B-A dye by novel white rot
      fungal consortium was studied in static and shaking conditions using solid state
      fermentation technology. Daldinia concentrica (DC) and Xylaria polymorpha (XP)
      consortium showed dye removal efficiency than the individual strains within 5
      days. The enzymes analysis revealed significant inductions in laccase (84%),
      lignin peroxidase (78%) and manganese peroxidase (65%) by the fungal co-culture
      (DC + XP), Xylaria polymorpha (XP) and Daldinia concentrica (DC) respectively.
      Enhanced decolorization was recorded when the medium was supplemented with
      glucose and ammonium nitrate as carbon and nitrogen sources respectively. The
      GCMS and HPLC analysis of metabolites suggest the different fates of
      biodegradation of cibracron brilliant red 3B-A dye by DC, XP and DC + XP
      consortium. The isotherm and kinetic studies revealed the goodness of fit of the
      experimental data when subjected to Freundlich and pseudo-second order models
      respectively. Phytotoxicity studies revealed that the biodegradation of the
      cibracron brilliant red 3B-A dye by the DC + XP consortium and individual strains
      has also led to the detoxification of the pollutant. This study revealed the
      effectiveness of white rot fungi in the eco-friendly remediation of dye polluted
      environment.

PMID- 30118767
TI  - In vitro effect of Bothrops leucurus lectin (BLL) against Leishmania amazonensis
      and Leishmania braziliensis infection.
AB  - Leishmania amazonensis and Leishmania braziliensis are the main causative agents
      of American Tegumentary Leishmaniasis (ATL) in Brazil. As intracellular
      parasites, the infection by Leishmania species is dependent on the host immune
      response and the immunotherapy could be promissory for the development of new
      strategies to combat ATL. In this work we investigated the leishmanicidal
      potential of a galactose-binding lectin from the snake venom of Bothrops leucurus
      (BLL) during the infection with L. amazonensis and L. braziliensis. BLL inhibited
      the promastigote growth and viability of both species in a mechanism dependent on
      galactose and calcium. The treatment with BLL also decreases the survival of
      intracellular parasites for both species and induced profound ultrastructural
      changes on amastigotes without apparent damage to the host cells. The analysis of
      the cytokine profile revealed that BLL induced an increase in the proinflammatory
      cytokines IL-6 and TNF-alpha by infected macrophages in both species, but
      differed in relation to IL-1beta and IL-10 response. Future works using in vitro
      and in vivo models are necessary to support the use of these lectins as
      biotechnological tool in immunological studies.

PMID- 30118768
TI  - Culled banana resistant starch-soy protein isolate conjugate based emulsion
      enriched with astaxanthin to enhance its stability.
AB  - The conjugates of biomacromolecules such as proteins and polysaccharides have
      potential to stabilize the emulsion system and encapsulate valuable bioactive
      compounds for biofortification in food systems. In this study, native banana
      starch (NBS) was isolated from green culled banana and modified into resistant
      starch (type III) by lintnerization followed by autoclaving-cooling process,
      resulting in lintnerized-autoclaved banana starch (LABS). Soy protein isolate
      (SPI) was used for developing the polysaccharide-protein conjugates i.e. LABS-SPI
      conjugate and used as wall material to stabilize the oil-in-water emulsion
      system. LABS-SPI conjugate emulsions were subjected to in vitro digestion model
      and oxidative stability evaluation. Furthermore, the emulsion system was enriched
      with astaxanthin and evaluated for its stability. The chemical finger printing of
      LABS-SPI conjugates showed stretching in immine and enaminol group of Schiff's
      bases, the CN stretching of Amadori product. During in vitro digestion LABS-SPI
      conjugate emulsion showed that the presence of resistant starch had an influence
      on the droplet digestion process and significantly (p < 0.05) lower free fatty
      acid release compared to emulsions stabilized by SPI alone. LABS-SPI conjugate
      emulsion system demonstrated higher stability of astaxanthin at storage
      temperatures (6, 20 and 37  degrees C), and can be used for biofortification of
      food and pharmaceutical formulations.

PMID- 30118769
TI  - Structure based identification and biological evaluation of novel and potent
      inhibitors of PCAF catalytic domain.
AB  - p300/CBP Associated Factor (PCAF), a GNAT family member protein, represent a
      valid target for therapeutic interventions since its dysfunction has implicated
      in variety of diseases like cancer, diabetes, inflammatory diseases, etc. Despite
      its potential for therapeutics, only a small number of PCAF inhibitors were
      reported. Hence, in this study, the catalytic domain of PCAF was explored to
      screen novel, potent and cell permeable inhibitor from three small molecule
      databases like Life Chemical, Maybridge and Chembridge by using Structure Based
      Virtual Screening (SBVS) method. Further, Induced Fit Docking, Binding Free
      Energy calculation, Single Point Energy calculation and Molecular Dynamics
      Simulation were performed on selected hits. In silico results revealed that F2209
      0381 has higher binding energy of -109.722 and have greater cell permeability
      (QPPCaco = 1456.764; QPPMDCK = 742.941) than rest of hits. Cytotoxicity effect
      and protein expression analysis of F2209-0381 on A549 cells reveals that it
      exhibited strong inhibition with IC50 value of 58.31 MUg/ml and significantly
      reduced the expression of PCAF after 72 h time point. Thus, this study warrants
      that F2209-0381 could become a novel, potent and cell permeable drug of PCAF
      thereby it could combat its mediated diseases.

PMID- 30118770
TI  - A new hypoglycemic mechanism of catalpol revealed by enhancing MyoD/MyoG-mediated
      myogenesis.
AB  - AIMS: Enhancing myogenesis has been identified as a possible target to improve
      insulin sensitivity and protect against metabolic diseases. Catalpol, an iridoid
      glycoside, has been shown to exert a hypoglycaemic effect by improvement of
      insulin sensitivity; however, the underlying mechanism remains unknown. In this
      study, we tested whether catalpol has the potential to improve insulin
      sensitivity by augmenting myogenesis. MAIN METHODS: We examined the hypoglycaemic
      mechanism of catalpol in db/db mice and C2C12 cells. db/db mice were treated with
      catalpol (200 mg/kg) for 8 consecutive weeks. Serum analysis, skeletal muscle
      performance and histology, and gene and protein expression were performed. In
      vitro glucose uptake, gene and protein expression were determined, and small
      interfering RNA was used to identify the underlying hypoglycaemic mechanism of
      catalpol. KEY FINDINGS: In this study, we tested whether catalpol has the
      potential to improve skeletal insulin sensitivity by augmenting myogenesis, in
      which we found that, catalpol treatment in db/db mice lowered blood glucose and
      improved insulin sensitivity via activation of phosphatidylinositol-3-Kinase
      (PI3K)/protein kinase B (AKT) pathway. Moreover, catalpol-treated mice exhibited
      enhanced myogenesis, as evidenced by increased myogenic differentiation (MyoD),
      myogenin (MyoG) and myosin heavy chain (MHC) expressions. The in vitro
      experimental results showed that both catalpol and metformin enhanced glucose
      uptake via activation of PI3K/AKT pathway. However, unlike metformin, the
      PI3K/AKT pathway activation by catalpol was dependent on enhanced MyoD/MyoG
      mediated myogenesis. SIGNIFICANCE: Improvement of insulin sensitivity by
      enhancing MyoD/MyoG-mediated myogenesis may constitute a new therapeutic approach
      for treating type 2 diabetes.

PMID- 30118771
TI  - The usefulness of short-term high-fat/high salt diet as a model of metabolic
      syndrome in mice.
AB  - Diabetic cardiomyopathy (DC) describes diabetes-associated changes in the
      structure and function of myocardium that are not directly linked to other
      factors such as hypertension. Currently there are some models of DC; however,
      they take a large time period to mimic key features. In the present study, we
      investigated the effects of a short-term high-fat/high salt diet (HFHS) treatment
      on myocardial function and structure, and vascular reactivity in C57BL/6 male
      mice. After 14 weeks HFHS induced hypertension (MAP = 144.95 +/- 16.13 vs 92.90
      +/- 18.95 mm Hg), low glucose tolerance (AUC = 1049.01 +/- 74.79 vs 710.50 +/-
      52.57 a.u.), decreased insulin sensitivity (AUC = 429.83 +/- 35.22 vs 313.67 +/-
      19.55 a.u.) and increased adiposity (epididymal fat weight 0.96 +/- 0.10 vs 0.59
      +/- 0.06 OW/BW * 102), aspects present in metabolic syndrome. Cardiac evaluation
      showed diastolic dysfunction (E/A ratio = 1.20 vs 1.90 u.a.) and cardiomyocyte
      hypertrophy (cardiomyocyte area = 502.82 +/- 31.46 vs 385.58 +/- 22.11 MUm2).
      Lastly, vascular reactivity was impaired with higher contractile response (136.10
      +/- 3.49 vs 120.37 +/- 5.43%) and lower response to endothelium-dependent
      vasorelaxation (74.01 +/- 4.35 vs 104.84 +/- 3.57%). In addition, the diet was
      able to induce an inward coronary remodeling (vascular total area: SCNS 6185 +/-
      800.6 vs HFHS 4085 +/- 213.7 MUm2). Therefore, we conclude that HFHS short-term
      treatment was able to induce metabolic syndrome-like state, cardiomyopathy and
      vascular injury working as an important tool to study cardiometabolic diseases.

PMID- 30118772
TI  - Effects of long-term oral nitrate administration on adiposity in normal adult
      female rats.
AB  - INTRODUCTION: Nitric oxide (NO) deficiency is associated with obesity. Nitrate
      could act as a substrate for production of NO and is a novel therapeutic agent in
      obesity. This study aims at determining effects of long-term nitrate
      administration on obesity indices in normal adult female rats. METHODS: Female
      Wistar rats were divided into four groups (n = 10/each): i.e. control group
      received tap water and three treatment groups received water containing 50, 100
      and 150 mg/L sodium nitrate for 6 months. Body weight (g) was measured monthly;
      naso-anal length (cm) and obesity indices including body mass index (BMI), Lee
      index, abdominal and thoracic circumferences were determined every two months.
      Both white adipose tissue (WAT) and brown adipose tissue (BAT) were weighted and
      then adiposity index was calculated. In addition, level of NOx (nitrate +
      nitrite) in serum and adipose tissues were measured at the end of the study.
      RESULTS: Compared to controls, body weights and naso-anal length were
      significantly (P < 0.001) lower in all nitrate-treated rats. Compared to
      controls, nitrate-treated rats had also lower adiposity indices, BMI, Lee index,
      abdominal and thoracic circumferences (13%, 17% and 22% for BMI and 5%, 6% and 8%
      for lee index at dose 50, 100, and 150 mg/L, respectively). In addition, nitrate
      administration increased NOx levels in serum and adipose tissues. CONCLUSIONS:
      Long-term nitrate administration has favorable effects on adiposity. It increases
      brown and decreases white adipose tissues in normal female rats; these
      observations could potentially help in management of obesity.

PMID- 30118773
TI  - Chronic corticosterone increases DeltaFOSB and CRFR1 immunoreactivity in brain
      regions that modulate aversive conditioning.
AB  - Previous studies showed that chronic treatment with corticosterone facilitates
      elevated T-maze (ETM) inhibitory avoidance and a step-down avoidance task,
      responses that have been used to investigate aversive conditioning and memory
      processes. On the other hand, chronic corticosterone does not alter ETM escape
      from the open arms. The purpose of the present study was to further investigate
      the effects of chronic corticosterone treatment (200 mg pellets, 21-day release)
      in an animal model of anxiety that does not involve aversive conditioning: the
      light/dark transition model. We also investigated the pattern of DeltaFosB
      immunoreactivity (DeltaFosB-ir) in different brain regions. To examine how
      treatment with chronic corticosterone interferes with CRFR1 expression we
      measured CRFR1 in the same brain structures that exhibited increased DeltaFosB
      ir. Results showed that chronic treatment with corticosterone did not alter
      behavioral measurements performed in the light/dark transition model. On the
      other hand, DeltaFosB-ir was increased in several structures that modulate
      aversive conditioning: the cingulate cortex, the ventro and dorsolateral septum,
      the amygdala, the paraventricular, dorsomedial and ventromedial hypothalamus, the
      periaqueductal grey matter, the dorsal raphe, and the median raphe nucleus.
      Chronic treatment with corticosterone also increased CRFR1-immunoreactivity in
      the ventrolateral septum, central amygdala, dorsomedial hypothalamus, ventral
      region of the dorsal raphe and median raphe. These results contribute to a better
      understanding of the behavioral and neurobiological alterations induced by
      chronic exposure to glucocorticoids.

PMID- 30118774
TI  - Neuroprotective effects of bergenin in Alzheimer's disease: Investigation through
      molecular docking, in vitro and in vivo studies.
AB  - Alzheimer's disease (AD) is an enervating and chronic progressive
      neurodegenerative disorder, occurring frequently in the elderly and adversely
      affecting intellectual capabilities and the cognitive processes. Bergenin
      possesses efficacious antioxidant, antiulcerogenic, anti-HIV, hepatoprotective,
      neuroprotective, anti-inflammatory and immunomodulatory activity along with
      antinociceptive effect and wound healing properties. Previous studies have shown
      that bergenin has in vitro bovine adrenal tyrosine hydroxylase inhibitory
      activity, mushroom tyrosinase inhibitory activities, beta-secretase (BACE-1)
      enzyme inhibitory activity and prevented neuronal death in the primary culture of
      rat cortical neurons. Protein tyrosine phosphatase-1B (PTP1B) is an intriguing
      target for anticancer and antidiabetic drugs and has recently been implicated to
      act as a positive regulator of neuroinflammation. Bergenin is also found to
      inhibit human protein tyrosine phosphatase-1B (hPTP1B) in vitro. Thus, bergenin
      was screened by molecular docking study using GOLD suite (version 5.2), CCDC for
      predicting its activity against targets of AD management like
      acetylcholinesterase (AChE) (1B41), butyrylcholinesterase (BuChE) (1P0I), Tau
      protein kinase 1 (GSK-3beta) (1J1B), BACE-1 (1FKN) wherein the GOLD score and
      fitness of bergenin were comparable to those of standard drugs like donepezil,
      galanthamine, physostigmine, etc. Bergenin demonstrated dose-dependent inhibition
      of both AChE and BuChE in vitro and found to be safe up to 50 MUM when screened
      in vitro on SH-SY5Y cell lines by cytotoxicity studies using MTT and Alamar blue
      assays. It also led to dose-dependent prevention of NMDA induced toxicity in
      these cells. Pretreatment with bergenin (14 days) in rats at three dose levels
      (20, 40 and 80 mg/kg; p.o.) significantly (p < 0.01) and dose-dependently
      alleviated amnesia induced by scopolamine (2 mg/kg, i.p.). The therapeutic effect
      of bergenin supplementation for 28 days, at three dose levels, was also evaluated
      in streptozotocin (3 mg/kg, ICV, unilateral) induced AD model in Wistar rats
      using Morris water maze and Y maze on 7th, 14th, 21st and 28th days. STZ caused
      significant (p < 0.001) cognitive impairment and cholinergic deficit and
      increased oxidative stress in rats. Bergenin could significantly ameliorate STZ
      induced behavioral deficits, inhibit the AChE and BuChE activity in parallel with
      an increase in the diminished GSH levels in a dose-dependent fashion. The
      histopathological investigations were also supportive of this datum. The bergenin
      treatment at 80 mg/kg led to significant (p < 0.05) abatement of the raised Abeta
      1-42 levels and alleviated the perturbed p- tau levels leading to significantly
      low (p < 0.01) levels of p-tau in brain homogenates of rats as compared to ICV
      STZ injected rats. In conclusion, the observed effects might be attributed to the
      cholinesterase inhibitory activity of bergenin coupled with its antioxidant
      effect, anti-inflammatory activity and reduction of Abeta-1-42 and p-tau levels
      which could have collectively helped in the attenuation of cognitive deficits.
      The current findings of the study are indicative of the promising preventive and
      ameliorative potential of bergenin in the management of AD through multiple
      targets.

PMID- 30118775
TI  - Recommendations for Safe and Efficient Morcellation After Endoscopic Enucleation
      of the Prostate.
AB  - OBJECTIVE: Background:After EEP (HoLEP, ThuLEP, GreenLEP or bipolar) the
      enucleated tissue is removed through a process of mechanical morcellation.
      Morcellation is the last, and very important, step in EEP procedures. It
      introduces additional time, and the possibility for complications exists.
      Although this is not a difficult procedure, it requires a learning curve that can
      pose a challenge for inexperienced surgeons. There are two types of morcellation
      systems: oscillating and reciprocating (depending on blade movement). OBJECTIVE:
      To demonstrate tips and tricks for safe and efficient morcellation after EEP and
      to share our experience with the oscillating morcellation system. MATERIAL AND
      METHODS: Four hundred and thirty-six patients were treated with green laser
      enucleation of the prostate by 3 surgeons with the en bloc technique between June
      2013 and November 2016. After completing the enucleation procedure we removed the
      adenoma with an oscillating mechanical morcellator (Piranha, Richard Wolf,
      Germany). We have reported our experience (including the learning curve) and
      collected multiple videos exemplifying not only proper techniques for safe
      morcellation, but also possible problems and their solutions. The authors have
      compiled their collective experience to offer tips and tricks as well as a
      practical approach to trouble shooting and problem solving of the morcellation
      procedure. RESULTS: The median morcellation time was 5.00 minutes (3.00; 10.0)
      and the median morcellation efficiency was 11.0 g/min (7.70; 16.0). Complications
      included 2 cases of superficial bladder injuries and no bladder perforations.
      CONCLUSION: Morcellation is a safe and appropriate procedure to remove the
      adenoma after endoscopic enucleation of the prostate. However, without taking
      proper precautions major complications can occur. This video serves as a guide
      for safe morcellation after EEP and also offers practical advice to help avoid
      the most common complications in this procedure.

PMID- 30118776
TI  - Evaluation of Sexual Dysfunction, Lower Urinary Tract Symptoms and Quality of
      Life in Men With Obstructive Sleep Apnea Syndrome and the Efficacy of Continuous
      Positive Airway Pressure Therapy.
AB  - OBJECTIVE: To determine the presence of lower urinary tract symptoms (LUTS),
      nocturia, sexual dysfunction (SD), and the status of quality of life (QOL) in men
      with obstructive sleep apnea syndrome (OSAS) and after continuous positive airway
      pressure (CPAP) treatment, the changes in the presence of these conditions and
      the improvements of QOL. MATERIALS AND METHODS: In this study, 126 patients with
      suspicious diagnosis of OSAS were enrolled prospectively. International Prostate
      Symptom Score (IPSS), International Consultation on Incontinence Questionnaire
      Male LUTS (ICIQ-MLUTS), Overactive Bladder Symptoms Score (OABS-V8), Nocturia
      Quality of Life (Nqol), voiding diary, International Index of Erectile Function
      (IIEF-15) questionnaire, and Short form 36 (SF-36) to assess the presence of SD,
      LUTS, nocturia, and the status of QOL were filled by patients before
      polysomnography. The same forms were filled in the third month of treatment by
      the patients directed to CPAP treatment due to moderate and severe OSAS. RESULTS:
      There were significant differences in IPSS, IIEF, OABSS, ICIQ-MLUTS, Nqol and SF
      36 scores, frequency of nocturia, and night-time urine volume according to OSAS
      severity. Among the factors affecting the QOL, there was strong correlation
      between ED and SF-36 sub-domains compared with the other factors. After CPAP
      treatment significant changes and improvements on these symptoms and QOL were
      observed. CONCLUSION: In patient with OSAS, the severity of SD and LUTS and their
      effect on QOL differ according to the severity of OSAS and CPAP treatment
      improves the negative impact of these conditions on QOL.

PMID- 30118777
TI  - Mapping molecular HLA typing data to UNOS antigen equivalents.
AB  - BACKGROUND: Histocompatibility labs must convert molecular HLA typing data to
      antigen equivalencies for entry into the United Network for Organ Sharing (UNOS)
      UNet system. While an Organ Procurement and Transplantation Network (OPTN) policy
      document provides general guidelines for conversion, the process is complex
      because no antigen mapping table is available. We present a UNOS antigen
      equivalency table for all IPD-IMGT/HLA alleles at the A, B, C, DRB1, DRB3/4/5,
      DQA1, and DQB1 loci. METHODS: An automated script was developed to generate a
      UNOS antigen equivalency table. Data sources used in the conversion algorithm
      included the World Marrow Donor Association (WMDA) antigen table, the HLA
      Dictionary, and UNOS-provided tables. To validate antigen mappings, we converted
      National Marrow Donor Program (NMDP) high resolution allele frequencies to
      antigen equivalents and compared with the UNOS Calculated Panel Reactive
      Antibodies (CPRA) reference panel. RESULTS: Normalized frequency similarity
      scores between independent NMDP and UNOS panels for 4 US population categories
      (Caucasian, Hispanic, African American and Asian/Pacific Islander) ranged from
      0.85 to 0.97, indicating correct antigen mapping. An open source web application
      (ALLele to ANtigen ("ALLAN")) and web services were also developed to map
      unambiguous and ambiguous HLA typing data to UNOS antigen equivalents based on
      NMDP population-specific allele frequencies (http://www.transplanttoolbox.org).
      CONCLUSIONS: Computer-assisted interpretation of molecular HLA data may aid in
      reducing typing discrepancies in UNet. This work also sets a foundation for
      molecular typing data to be utilized directly in the UNet match run as well as
      the virtual crossmatch process at transplant centers.

PMID- 30118778
TI  - Human Herpes simplex 1 virus infection of endometrial decidual tissue-derived MSC
      alters HLA-G expression and immunosuppressive functions.
AB  - OBJECTIVES: Mesenchymal stromal/stem cells have immunosuppressive functions. Our
      previous results demonstrated that one of the players of this immunomodulation
      can be ascribed to the Human Leukocyte Antigen-G. HLA-G, a non classical HLA
      class I antigen, is involved in immune tolerance during pregnancy, organ
      transplantation, autoimmune and inflammatory diseases. In this study we wanted to
      verify whether human endometrial decidual tissue derived (EDT)-MSC could express
      HLA-G. Additionally we assessed the permissivity to Human Herpesvirus infections,
      using HSV-1 as a model, and the possible effect on EDT-MSC immunosuppressive
      functions towards peripheral blood mononuclear cell (PBMC) proliferation.
      METHODS: We analyzed immune-inhibitory functions and HLA-G expression in human
      EDT-MSC before and after HSV-1 infection. RESULTS: We observed that EDT-MSC
      express HLA-G molecules, that partly are responsible for the immune-inhibitory
      functions of EDT-MSC towards PBMC proliferation. EDT-MSC are permissive for a
      productive infection by HSV-1, that decreases HLA-G expression and affects EDT
      MSC immune-inhibitory functions. CONCLUSIONS: We demonstrate that EDT-MSC are
      susceptible to HSV-1 infection, that reduces HLA-G expression and their immune
      inhibitory function. These data could have a clinical implication in the use of
      EDT-MSC as an immunosuppressant, in particular in steroid-refractory GvHD after
      allogeneic hematopoietic stem cell transplantation and in autoimmune diseases.

PMID- 30118779
TI  - Development of an extraction method for anabolic androgenic steroids in dietary
      supplements and analysis by gas chromatography-mass spectrometry: Application for
      doping-control.
AB  - Several studies have highlighted that nutritional supplements may contain
      undeclared anabolic steroids that are banned by the International Olympic
      Committee/World Anti-Doping Agency. Any kind of abuse with these drugs is
      extremely dangerous because of their side effects. Thus, the control of food
      additives in order to protect the best consumer health and to limit fraudulent
      practices in the field of sports is essential. This paper describes a simple and
      effective qualitative gas chromatography-mass spectrometry (GC-MS) method to
      detect anabolic androgenic steroids (AAS): androsterone, nandrolene,
      dehydroepiandrosterone, 5alpha-androstane-3beta, 17beta-diol,
      dihydrotestosterone, testosterone, methenolone acetate, methandienone, boldenone
      and fluoxymesterone, in food supplements. Methyltestosterone was used as internal
      standard. Target compounds were extracted with a mixture of N-pentane and di
      ethylether (7.5:2.5, v/v). A good extraction recovery was obtained by our method
      for all the AAS (R > 88%). Crude extract was derivatized with N-methyl-N
      trimethylsilyl-trifluoracetamide. Separation was performed on a GC connected to
      quadrupole MS detector using a 5% phenylmethylsiloxane fused silica capillary
      column (30 m * 0.25 mm i.d.; film thickness, 0.25 um). Helium was used as carrier
      gas with a flow rate of 0.3 ul min-1 (measured at 6.1 psi 190  degrees C). The MS
      was operated in electron ionization mode (70 eV) and in selected ion monitoring
      (SIM). The mass spectra of the standard compounds were acquired in full SCAN mode
      (50-700 m/z) by infusion of a reference solution at 50 ug/ml. Three higher
      diagnostic ions were monitored for each compound of interest. All AAS get
      separated with good peak shapes and resolution factor. The total analysis time by
      our optimised method was only 20 min. The developed method was validated
      according to Laboratories International Standard regulations for specificity,
      precision in both liquid and solid matrixes, and memory effect. The Tolerance
      Interval was judged true. The limit of detection was about 10 ng/g for solid
      samples and 10 ng/ml for liquid samples. The developed method was then applied to
      the research of steroids in nine Tunisian commercially dietary supplements using
      for each compound of interest SIM mode for screening then SCAN mode for
      confirmation. One of the monitoring samples was positive to methandienone not
      declared on the label. Our analytical method can be beneficial for AAS screening
      in dietary supplements.

PMID- 30118780
TI  - Potential application of testosterone replacement therapy as treatment for
      obesity and type 2 diabetes in men.
AB  - Sedentary lifestyle and over-nutrition are the main causes of obesity and type 2
      diabetes (T2D). However, the same causes are major triggers of hypogonadism. Many
      T2D patients show low testosterone levels while hypogonadal men seem to be prone
      to become diabetic. Testosterone plays a major role in the regulation of muscle
      mass, adipose tissue, inflammation and insulin sensitivity and is therefore
      indirectly regulating several metabolic pathways, while T2D is commonly triggered
      by insulin resistance, increased adipose tissue and inflammation, showing a
      negative correlation between testosterone levels and T2D. Testosterone
      replacement therapy (TRT) is widely used in patients with symptoms of
      hypogonadism, however it is not commonly used as preventive intervention or
      treatment for T2D patients even though hypogonadal patients share many common
      symptoms (obesity, insulin insensitivity, increased inflammation, decrease in
      muscle mass and strength) with T2D patients. Even though TRT is often associated
      with side effects such as prostatic hypertrophy or cancer, cardiovascular risks
      due to increase in the number of red blood cells and infertility, several studies
      have shown that TRT remains a potent intervention improving metabolic functions
      such as glycated haemoglobin, blood sugar, total cholesterol and visceral fat.
      The purpose of this review is to discuss the possible benefits and risks of TRT
      in the prevention and treatment of obesity and T2D and assess the health risks
      and benefits of common T2D medications and testosterone.

PMID- 30118781
TI  - Mitochondrial genome of the yellow catfish Pelteobagrus fulvidraco and insights
      into Bagridae phylogenetics.
AB  - The mitochondrial genome (mitogenome) can provide important information for
      understanding phylogenetic analysis and molecular evolution. Herein, we amplified
      the complete mitogenome sequence of Pelteobagrus fulvidraco. The mitogenome was
      16,526 bp in length and included 13 protein-coding genes (PCGs), 22 transfer RNA
      genes, two ribosomal RNA genes and a non-coding control region (D-loop). Both the
      organization and location of genes in the mitogenome were consistent with those
      from Siluriformes fishes previously published in GenBank. The phylogenetic
      relationships based on Bayesian inference (BI) and Maximum likelihood (ML)
      methods showed that P. fulvidraco has close relationships with Pelteobagrus
      eupogon and Tachysurus intermedius, suggesting that P. fulvidraco belongs to
      Tachysurus. This study provides evidence that Tachysurus, Pseudobagrus and
      Leiocassis do not form monophyly, but that these three genera form a monophyletic
      group. Our results provide reference for further phylogenetic research of the
      Bagridae species.

PMID- 30118782
TI  - Association study of Disrupted-In-Schizophrenia-1 gene variants and tardive
      dyskinesia.
AB  - Tardive dyskinesia (TD) is an involuntary movement disorder that occurs in ~20%
      of patients after extended antipsychotic use. Its pathophysiology is unclear;
      however, familial patterns and gene association studies indicate an inherited
      component to risk. The disrupted in schizophrenia 1 (DISC1) gene was selected for
      analysis because it interacts with and regulates two important proteins involved
      in antipsychotic medication action: the dopamine D2 receptor and the cAMP
      phosphodiesterase type IVB (PDE4B). The D2 receptor is the obligate target of all
      existing antipsychotic medications, and PDE4B hydrolyzes cAMP, a core signaling
      molecule activated by agonist binding to the D2 receptor. Notably, PDE4B
      inhibitors such as rolipram have been shown to reduce TD-like behaviours in
      animal models. Nine single-nucleotide polymorphisms (SNPs) in the DISC1 gene were
      investigated in a sample of 193 chronic schizophrenia patients for association
      with the presence and severity of TD, with age and sex as additional variables.
      TD severity was measured using the Abnormal Involuntary Movement Scale (AIMS).
      Two DISC1 SNPs were associated with TD severity (uncorrected p < 0.05), but these
      findings did not survive correction for multiple testing. This preliminary
      investigation suggests that DISC1 gene variants do not affect risk for TD or
      severity.

PMID- 30118784
TI  - Positive impact of a cooking skills intervention among Brazilian university
      students: Six months follow-up of a randomized controlled trial.
AB  - OBJECTIVES: The purpose of this study was to determine the effects of the
      Nutrition and Culinary in the Kitchen (NCK) Program to evaluate the improvement
      of cooking skills and healthy eating of university students. METHODS: A
      randomized controlled trial with six months follow-up was used incorporating an
      intervention group (IG) and a control group (CG). The IG participated in the NCK
      program over a six-week period, three hours weekly, based on five hands-on
      cooking classes and one food market visit, while CG continued their usual
      activities. Outcome measures included changes in relation to a) accessibility and
      availability of fruits and vegetables (AAFV); b) cooking attitudes (CA); c)
      cooking behaviors at home (CBH); d) cooking behaviors away from home (CBAH) e)
      produce consumption self-efficacy (SEPC); f) self-efficacy for using cooking
      techniques (SECT); g) self-efficacy for using fruits, vegetables, and seasonings
      (while cooking) (SEFVS); and h) knowledge of cooking terms and techniques (CTT).
      An online self-completed validated survey was answered, at three time points:
      baseline (T1), after intervention (T2) and six months after intervention (T3).
      Statistical analyses were conducted to evaluate changes in outcomes within and
      between groups over time. RESULTS: 76 students completed the online questionnaire
      at the 3 time points. Findings revealed a statistically significant increase (p <
      0.05) in all outcomes evaluated in the IG, except for CBH and CBAH. This effect
      was sustained at T3 (p < 0.001). Results were similar to the adjusted model (p <
      0.001), thus, indicating that IG changes, when compared to CG, were due to the
      intervention effect. CONCLUSION: NCK culinary intervention program demonstrated
      efficacy for the increased on AAFV, CA, SEPC, SECT, SEFVS and CTT with university
      students.

PMID- 30118785
TI  - RYGB increases the satiating effect of intrajejunal lipid infusions in female
      rats.
AB  - We used a novel rat model to investigate the physiological bases of early
      satiation after Roux-en-Y gastric bypass surgery (RYGB). Female rats were
      subjected to RYGB or sham surgery. Chronic infusion catheters were placed in the
      Roux limb of RYGB rats and the corresponding anatomical locus of the jejuna of
      sham-RYGB rats. Rats were also ovariectomized and chronically treated with either
      estradiol (E2; 2 MUg each 4th day SC) or the oil vehicle. Testing was begun 10-12
      wk after surgery. Intrajejunal lipid infusions (10 min, 4.4 mL, 8.8 kcal) were
      performed just before test meals of a low-energy artificially sweetened gel diet
      (0.1 kcal/g) that RYGB rats ingest avidly. Intrajejunal lipid infusions reduced
      test-meal size more in RYGB rats than sham-operated rats, indicating that, at
      least after prolonged adaptation to surgery, the satiating actions of lipids
      acting intra- or post-jejunally are increased by RYGB and that accelerated meal
      appearance in the intestines after RYGB is not necessary for this effect. The
      satiating effects of intrajejunal lipid infusions were similar in E2-and oil
      treated rats, suggesting that the effect was not dependent on an activational
      effect of estrogens. In a second experiment, pretreatment with the
      cholecystokinin A-receptor antagonist devazepide reduced the satiating effect of
      intrajejunal lipid infusions in E2-treated RYGB rats. Although these data are
      preliminary due to the smaller numbers of rats than in the first experiment, they
      suggest that cholecystokinin-mediated jejunal satiation contributes to early
      satiation after RYGB in ovariectomized rats with peri-ovulatory levels of
      estradiol. The results of these experiments may be relevant to understanding RYGB
      outcome in pre- and postmenopausal women.

PMID- 30118787
TI  - Informal learning and food sense in home cooking.
AB  - This exploratory article examines the novel term food sense and informal learning
      in the context of home cooking. Its theory draws from Dewey's work and from his
      notions of reflexive thought and action. The data consist of a transcribed audio
      recording of an in-depth, video-based, stimulated-recall (SR) interview. The auto
      ethnographic videos were used to stimulate conversation during the interview and
      were previously collected as part of a broader research project on home cooking
      in a Finnish family context. Based on the theory and the data, the definition of
      food sense was refined into a model consisting of three levels: 'Understanding'
      as the ability to define and interpret emerging ruptures in activity; 'Applying'
      as the competence to plan and execute solutions that function in context; and 'Re
      defining' as the reformulation of activities to enable new ways of doing. In
      reference to the empirical examples, two of the three episodes represented
      'Understanding' and 'Applying'; whereas the third example included also the
      potential for re-defining habitual ways of action. However, despite possession of
      relevant knowledge and initial motivation, the emergence of negative emotions of
      the person in charge of the cooking process prevented reformulating existing
      cooking habits. By providing novel insights into the social, cultural, and
      situated nature of home cooking, the article complements the more individual
      focused and/or knowledge-based approaches used by other recent studies of cooking
      skills and learning.

PMID- 30118786
TI  - Is it still a real treat? Adults' treat provision to children.
AB  - Consumption of high-energy foods in the absence of hunger has been identified as
      a key target to address in the area of obesity. For children, such foods are
      often provided by adults as treats. There is limited understating of adults'
      treat giving. The present study aimed to understand adults' provision of treats
      to children on the Island of Ireland. A total of 1039 participants, including
      parents, grandparents, child minders and education practitioners completed a face
      to-face survey in their home. Participants defined their treats for children
      primarily as 'something nice', 'deserved/earned' and 'something special'. The top
      three motivations for treat foods provision were 'to reward for good behaviour'
      (42.3%), 'because the child(ren) ask' (42.2%) and 'to make the child(ren) feel
      better' (29.4%). Almost all participants would provide treat foods at
      celebrations and 52.5% always did so. In addition, 68% participants had
      structured weekly and/or daily treat for children. Treats provided to children
      were dominated by energy-dense foods. The top three were sweets, chocolates and
      ice-creams, being used by 45.2%, 45.1% and 38.8% participants. Variations were
      observed across different adult groups, in terms of their treat giving behaviour.
      The main observation was that adults' treat foods provision has become habitual.
      The findings can help develop targeted strategies to encourage the reduction or
      replacement of food treats for children.

PMID- 30118788
TI  - Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review.
AB  - The development of oral dosage forms for poorly water-soluble active
      pharmaceutical ingredients (APIs) is a persistent challenge. A range of methods
      has been explored to address this issue, and amorphous solid dispersions (ASDs)
      have received increasing attention. ASDs are typically prepared by starting with
      a liquid precursor (a solution or melt) and applying energy for solidification.
      Many techniques can be used, with the emergence of electrospinning as a potent
      option in recent years. This method uses electrical energy to induce changes from
      liquid to solid. Through the direct applications of electrical energy,
      electrospinning can generate nanofiber-based ASDs from drug-loaded solutions,
      melts and melt-solutions. The technique can also be combined with other
      approaches using the application of mechanical, thermal or other energy sources.
      Electrospinning has numerous advantages over other approaches to produce ASDs.
      These advantages include extremely rapid drying speeds, ease of implentation,
      compatibility with a wide range of active ingredients (including those which are
      thermally labile), and the generation of products with large surface areas and
      high porosity. Furthermore, this technique exhibits the potential to create so
      called 'fifth-generation' ASDs with nanostructured architectures, such as
      core/shell or Janus systems and their combinations. These advanced systems can
      improve dissolution behaviour and provide programmable drug release profiles.
      Additionally, the fiber components and their spatial distributions can be
      precisely controlled. Electrospun fiber-based ASDs can maintain an incorporated
      active ingredient in the amorphous physical form for prolonged periods of time
      because of their homogeneous drug distribution within the polymer matrix
      (typically they comprise solid solutions), and ability to inhibit molecular
      motion. These ASDs can be utilised to generate oral dosage forms for poorly water
      soluble drugs, resulting in linear or multiple-phase release of one or more APIs.
      Electrospun ASDs can also be exploited as templates for manipulating molecular
      self-assembly, offering a bridge between ASDs and other types of dosage forms.
      This review addresses the development, advantages and pharmaceutical applications
      of electrospinning for producing polymeric ASDs. Material preparation and
      analysis procedures are considered. The mechanisms through which performance has
      been improved are also discussed.

PMID- 30118789
TI  - The emerging landscape of circular RNA in cardiovascular diseases.
AB  - Circular RNAs (circRNAs), a large novel type of endogenous transcripts, have
      become a new research hotspot in the field of RNA biology. CircRNAs are mainly
      generated from exons or introns via multiple mechanisms, and the majority of
      circRNAs are stable and conserved across different species. Recent studies have
      revealed that circRNAs can function as miRNA sponges, binding partners of
      proteins, regulators of transcription, or can even be translated into proteins.
      Growing evidence has demonstrated that circRNAs play important roles in a wide
      variety of biological processes such as cell proliferation, apoptosis and
      senescence, and may serve as potential diagnostic biomarkers or therapeutic
      targets for various cardiovascular diseases. Here, we review the biogenesis,
      properties and biological function of circRNAs, and summarize their roles in
      cardiovascular disorders.

PMID- 30118790
TI  - Ischemic preconditioning protects against cardiac ischemia reperfusion injury
      without affecting succinate accumulation or oxidation.
AB  - Ischemia-reperfusion (IR) injury occurs when blood supply to an organ is
      disrupted and then restored, and underlies many disorders, notably myocardial
      infarction and stroke. While reperfusion of ischemic tissue is essential for
      survival, it also initiates cell death through generation of mitochondrial
      reactive oxygen species (ROS). Recent work has revealed a novel pathway
      underlying ROS production at reperfusion in vivo in which the accumulation of
      succinate during ischemia and its subsequent rapid oxidation at reperfusion
      drives ROS production at complex I by reverse electron transport (RET).
      Pharmacologically inhibiting ischemic succinate accumulation, or slowing
      succinate metabolism at reperfusion, have been shown to be cardioprotective
      against IR injury. Here, we determined whether ischemic preconditioning (IPC)
      contributes to cardioprotection by altering kinetics of succinate accumulation
      and oxidation during IR. Mice were subjected to a 30-minute occlusion of the left
      anterior descending coronary artery followed by reperfusion, with or without a
      protective IPC protocol prior to sustained ischemia. We found that IPC had no
      effect on ischemic succinate accumulation with both control and IPC mice having
      profound increases in succinate compared to normoxia. Furthermore, after only 1
      minute reperfusion succinate was rapidly metabolised returning to near pre
      ischemic levels in both groups. We conclude that IPC does not affect ischemic
      succinate accumulation, or its oxidation at reperfusion.

PMID- 30118792
TI  - Hydrolyzing activities of phenyl valerate sensitive to organophosphorus compounds
      paraoxon and mipafox in human neuroblastoma SH-SY5Y cells.
AB  - The molecular targets of best known neurotoxic effects associated to acute
      exposure to organophosphorus compounds (OPs) are serine esterases located in the
      nervous system, although there are other less known neurotoxic adverse effects
      associated with chronic exposure to OPs whose toxicity targets are still not
      identified. In this work we studied sensitivity to the non-neuropathic OP
      paraoxon and to the neuropathic OP mipafox of phenyl valerate esterases (PVases)
      in intact and lysed human neuroblastoma SH-SY5Y cells. The main objective was to
      discriminate different unknown pools of esterases that might be potential targets
      of chronic effects from those esterases already known and recognized as targets
      to these acute neurotoxicity effects. Two components of PVases of different
      sensitivities were discriminated for paraoxon in both intact and lysed cells;
      while the two components inhibitable by mipafox were found only for intact cells.
      A completely resistant component to paraoxon of around 30% was found in both
      intact and lysed cells; while a component of slightly lower amplitude (around
      20%) completely resistant to mipafox was also found for both preparations (intact
      and lysed cells). The comparison of the results between the intact cells and the
      lysed cells suggests that the plasma membrane could act as a barrier that reduced
      the bioavailability of mipafox to PVases. This would imply that the
      discrimination of the different esterases should be made in lysed cells. However,
      those studies which aim to determine the physiological role of these esterases
      should be necessarily conducted in intact cultured cells.

PMID- 30118791
TI  - Anti-androgenic therapy with finasteride improves cardiac function, attenuates
      remodeling and reverts pathologic gene-expression after myocardial infarction in
      mice.
AB  - Maladaptive cardiac remodeling after myocardial infarction (MI) is increasingly
      contributing to the prevalence of chronic heart failure. Women show less severe
      remodeling, a reduced mortality and a better systolic function after MI compared
      to men. Although sex hormones are being made responsible for these differences,
      it remains currently unknown how this could be translated into therapeutic
      strategies. Because we had recently demonstrated that inhibition of the
      conversion of testosterone to its highly active metabolite dihydrotestosterone
      (DHT) by finasteride effectively reduces cardiac hypertrophy and improves heart
      function during pressure overload, we asked here whether this strategy could be
      applied to post-MI remodeling. We found increased abundance of DHT and increased
      expression of androgen responsive genes in the mouse myocardium after
      experimental MI. Treatment of mice with finasteride for 21 days (starting 7 days
      after surgery), reduced myocardial DHT levels and markedly attenuated cardiac
      dysfunction as well as hypertrophic remodeling after MI. Histological and
      molecular analyses showed reduced MI triggered interstitial fibrosis, reduced
      cardiomyocyte hypertrophy and increased capillary density in the myocardium of
      finasteride treated mice. Mechanistically, this was associated with decreased
      activation of myocardial growth-signaling pathways, a comprehensive normalization
      of pathological myocardial gene-expression as revealed by RNA deep-sequencing and
      with direct effects of finasteride on cardiac fibroblasts and endothelial cells.
      In conclusion, we demonstrated a beneficial role of anti-androgenic treatment
      with finasteride in post-MI remodeling of mice. As finasteride is already
      approved for the treatment of benign prostate disease, it could potentially be
      evaluated as therapeutic strategy for heart failure after MI.

PMID- 30118793
TI  - Cigarette smoke condensate alters Saccharomyces cerevisiae efflux transporter
      mRNA and activity and increases caffeine toxicity.
AB  - In animals, cigarette smoke may alter pharmacokinetics by altering activity and
      expression of ABC drug transporters. We previously demonstrated that cigarette
      smoke condensate (CSC) impairs activity and expression of several hepatic ABC
      drug transporters which mediate toxicant efflux. However, CSC effects on efflux
      transporters are still unknown in Saccharomyces cerevisiae which resists diverse
      chemical stresses, by inducing pleiotropic drug resistance (PDR) genes among
      others. The yeast ABC transporters are functionally and structurally homologous
      to the mammalian ones. In this study, Saccharomyces cerevisiae exposure to CSC
      for 15 min caused a dose-dependent inhibition of rhodamine 123 efflux, whereas a
      longer exposure (3 h) induced mRNA expression of the ABC PDR efflux pumps Pdr5,
      Snq2, Pdr 10 and Pdr15, and of Tpo1, a member of the major facilitator
      superfamily (MFS). CSC also increased toxicity of caffeine, which is handled by
      two PDR transporters, Pdr5 and Snq2. Taken together, these data demonstrated that
      yeast efflux transporters are targets of cigarette smoke chemicals, and that
      Saccharomyces cerevisiae may cope with CSC-induced stress, including the initial
      efflux inhibition, by induction of the mRNA of several plasma membrane PDR and
      MFS efflux transporters. Saccharomyces cerevisiae is therefore a valid model to
      investigate pollutant effects on ABC and MFS transporters.

PMID- 30118794
TI  - Evaluation of non-invasive biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4
      D) in saliva.
AB  - The objective of this study was to evaluate the potential for non-invasive
      biomonitoring of 2,4-Dichlorophenoxyacetic acid (2,4-D) in saliva. Using an in
      vitro rat salivary gland epithelial cell (SGEC) system, a collection of
      experiments investigating chemical protein binding, temporal and directional
      transport, as well as competitive transport with para-aminohippuric acid (PAH), a
      substrate for renal organic anion transporters, was conducted to identify
      cellular transport parameters required to computationally model salivary
      transport of 2,4-D. Additionally, a physiological protein gradient was
      implemented to mimic physiologically relevant concentrations of protein in rat
      plasma and saliva, and under these conditions the transfer of 2,4-D was markedly
      slower, driven by increased protein binding (i.e. reduced free 2,4-D species
      available to cross salivary barrier). The rate of transfer was directly
      proportional to the amount of unbound 2,4-D and demonstrated no indication of
      active transport. An in vivo assessment of 2,4-D exposure in rats revealed non
      linear protein binding in plasma, indicating saturated protein binding and
      increased levels of unbound 2,4-D species at higher doses. A strong correlation
      between 2,4-D concentrations in saliva and unbound 2,4-D in plasma was observed
      (Pearson correlation coefficient = 0.95). Saliva:plasma 2,4-D ratios measured in
      vivo (0.0079) were consistent within the linear protein binding range and
      expected 2,4-D levels from occupational exposures but were significantly
      different than ratios measured in vitro (physiological conditions) (0.034),
      possibly due to 2,4-D concentrations in saliva not being at equilibrium with 2,4
      D concentrations in blood, as well as physiological features absent in in vitro
      settings (e.g. blood flow). We demonstrated that 2,4-D is consistently
      transported into saliva using both in vitro and in vivo models, making 2,4-D a
      potential candidate for human non-invasive salivary biomonitoring. Further work
      is needed to understand whether current sensor limits of detection are sufficient
      to measure occupationally relevant exposures.

PMID- 30118795
TI  - Exploration of the establishment of manganese poisoning rat model and analysis of
      discriminant methods.
AB  - OBJECTIVE: We explored methods to establish an animal model of manganese
      poisoning and evaluate the feasibility of the determination method. METHODS:
      Twenty-four specific pathogen-free male rats were randomly divided into four
      groups: control, low-dose (15.0 mg/kg), middle-dose (25.0 mg/kg), and high-dose
      (50.0 mg/kg). Intraperitoneal injection of MnCl2.H2O was administered every 48 h
      for three months. Rats were tested for behavior, muscle tension, and with a
      balance beam experiment at the end of each month. Three months later, the rats
      were sacrificed and brain tyrosine hydroxylase (TH) expression levels were
      measured. RESULTS: Rats in each group exhibited changes in behavior, muscle tone,
      and balance after exposure to manganese, and the scores of each test for the high
      dose and middle-dose groups were statistically different from the low-dose and
      control groups. Finally, a rat model of manganese poisoning was identified with
      the TH expression less than 30% of the normal value. We find that the modeling
      success rate of the middle-dose and high-dose groups were 66.67% and 100%,
      respectively. In addition, there were negative correlations between the three
      assessment methods such as behavioral tests and TH expression levels.
      CONCLUSIONS: Intraperitoneal injection of MnCl2.H2O (25 mg/kg) can successfully
      establish a manganese poisoning rat model with low mortality rate. Muscle
      tension, balance beam, and behavioral tests can be used as preliminary
      determination methods for modeling.

PMID- 30118796
TI  - Targeting oncogenic Raf protein-serine/threonine kinases in human cancers.
AB  - The Ras-Raf-MEK-ERK signal transduction cascade is arguably the most important
      oncogenic pathway in human cancers. Ras-GTP promotes the formation of active
      homodimers or heterodimers of A-Raf, B-Raf, and C-Raf by an intricate process.
      These enzymes are protein-serine/threonine kinases that catalyze the
      phosphorylation and activation of MEK1 and MEK2 which, in turn, catalyze the
      phosphorylation and activation of ERK1 and ERK2. The latter catalyze the
      regulatory phosphorylation of dozens of cytosolic and nuclear proteins. The X-ray
      crystal structure of B-Raf-MEK1 depicts a face-to-face dimer with interacting
      activation segments; B-Raf is in an active conformation and MEK1 is in an
      inactive conformation. Besides the four traditional components in the Ras-Raf-MEK
      ERK signaling module, scaffolding proteins such as Kinase Suppressor of Ras
      (KSR1/2) play an important role in this signaling cascade by functioning as a
      scaffold protein. RAS mutations occur in about 30% of all human cancers.
      Moreover, BRAFV600E mutations occur in about 8% of all cancers making this the
      most prevalent oncogenic protein kinase. Vemurafenib and dabrafenib are B
      RafV600E inhibitors that were approved for the treatment of melanomas bearing the
      V600E mutation. Coupling MEK1/2 inhibitors with B-Raf inhibitors is more
      effective in treating such melanomas and dual therapy is now the standard of
      care. Vemurafenib and cobimetanib, dabrafenib and trametinib, and encorafenib
      plus binimetinib are the FDA-approved combinations for the treatment of BRAFV600E
      melanomas. Although such mutations occur in other neoplasms including thyroid,
      colorectal, and non-small cell lung cancers, these agents are not as effective in
      treating these non-melanoma neoplasms. Vemurafenib and dabrafenib produce the
      paradoxical activation of the MAP kinase pathway in wild type BRAF cells. The
      precise mechanism for this activation is unclear, but drug-induced Raf activating
      side-to-side dimerization appears to be an essential step. Although 63%-76% of
      all people with advanced melanoma with the BRAF V600E mutation derive clinical
      benefit from combination therapy, median progression-free survival lasts only
      about nine months and 90% of patients develop resistance within one year. The
      various secondary resistance mechanisms include NRAS or KRAS mutations (20%),
      BRAF splice variants (16%), BRAFV600E/K amplifications (13%), MEK1/2 mutations
      (7%), and non-MAP kinase pathway alterations (11%). Vemurafenib and dabrafenib
      bind to an inactive form of B-Raf (alphaC-helixout and DFG-Din) and are
      classified as type I1/2 inhibitors. LY3009120 and lifirafenib, which are in the
      early drug-development stage, bind to a different inactive form of B-Raf (DFG
      Dout) and are classified as type II inhibitors. Besides targeting B-Raf and MEK
      protein kinases, immunotherapies that include ipilimumab, pembrolizumab, and
      nivolumab have been FDA-approved for the treatment of melanomas. Current clinical
      trials are underway to determine the optimal usage of targeted and
      immunotherapies.

PMID- 30118797
TI  - CHST3 and CHST13 polymorphisms as predictors of bosentan-induced liver toxicity
      in Japanese patients with pulmonary arterial hypertension.
AB  - Bosentan, an endothelin receptor antagonist, has been widely used as a first-line
      drug for the treatment of pulmonary arterial hypertension (PAH). In addition,
      bosentan is approved for patients with digital ulcers related to systemic
      sclerosis. Liver dysfunction is a major adverse effect of bosentan and may lead
      to discontinuation of therapy. The purpose of this study was to identify genomic
      biomarkers to predict bosentan-induced liver injury. A total of 69 PAH patients
      were recruited into the study. An exploratory analysis of 1936 single-nucleotide
      polymorphisms (SNPs) in 231 genes involved in absorption, distribution,
      metabolism, and elimination of multiple medications using Affimetrix DMETTM (Drug
      Metabolism Enzymes and Transporters) chips was performed. We extracted 16 SNPs (P
      <  0.05) using the Jonckheere-Terpstra trend test and multiplex logistic
      analysis; we identified two SNPs in two genes, CHST3 and CHST13, which are
      responsible for proteoglycan sulfation and were significantly associated with
      bosentan-induced liver injury. We constructed a predictive model for bosentan
      induced liver injury (area under the curve [AUC]: 0.89, sensitivity: 82.61%,
      specificity: 86.05%) via receiver operating curve (ROC) analysis using 2 SNPs and
      2 non-genetic factors. Two SNPs were identified as potential predictive markers
      for bosentan-induced liver injury in Japanese patients with pulmonary arterial
      hypertension. This is the first pharmacogenomics study linking proteoglycan
      sulfating genes to drug-induced liver dysfunction, a frequently observed clinical
      adverse effect of bosentan therapy. These results may provide a way to
      personalize PAH medicine as well as provide novel mechanistic insights to drug
      induced liver dysfunction.

PMID- 30118798
TI  - Cardiac resynchronization therapy pacemakers versus defibrillators in older non
      ischemic cardiomyopathy patients.
AB  - INTRODUCTION: With the recent publication of the negative DANISH trial, the
      mortality benefit of the implantable cardioverter-defibrillator (ICD) has been
      put in question in patients with non-ischemic cardiomyopathy (NICM). Because a
      majority of patients in DANISH receive cardiac resynchronization therapy (CRT)
      devices, we investigated in the present study the survival of recipients of CRT
      pacemakers (CRT-P) versus CRT ICDs (CRT-D) in a cohort of older (>=75 years) NICM
      patients at our institution. METHODS: A total of 135 NICM patients with CRT
      device were identified (42 with CRT-P and 93 with CRT-D) and were followed to the
      endpoint of all-cause mortality. Overall survival was compared between the CRT-P
      and CRT-D groups with adjustment for differences in baseline characteristics.
      RESULTS: Over a median follow-up of 46 months from the time of CRT device
      implantation, there were 54 total deaths (40%): 14 in the CRT-P (33%) and 40 in
      the CRT-D (43%) groups. Overall, CRT-P recipients had similar unadjusted
      mortality compared to CRT-D recipients (hazard ratio [HR] 1.04, 95% confidence
      interval [CI] 0.56-1.93), and this remained unchanged after adjusting for
      unbalanced covariates (HR 0.95, 95% CI 0.47-1.89) including left ventricular
      ejection fraction, used of angiotensin converting enzyme inhibitors/angiotensin
      receptor blockers, and the Charlson comorbidity index. CONCLUSION: Our data
      support that in older NICM patients with CRT devices, the addition of ICD therapy
      does not improve survival.

PMID- 30118799
TI  - Langerin (CD207)-positive cells in leprosy: Possible implications for
      pathogenesis of the disease with special emphasis on dermal immunoreactivity.
AB  - Leprosy is a disease caused by Mycobacterium leprae, which is characterized by
      two distinct poles, the tuberculoid pole and the lepromatous pole, depending on
      the immune response to the bacillus. Langerin-positive cells are dendritic cells
      that appear to play an essential role in the development of the disease. These
      cells are specialized in the processing and presentation of antigens, exerting an
      important function in the activation of the immune system. To evaluate the
      expression of langerin-positive cells (CD207+) in skin lesion fragments of
      patients with a diagnosis of M. leprae infection and to associate the expression
      of these cells with the polar forms of the disease. Langerin-positive cells were
      detected in larger numbers in lesions of patients with the tuberculoid form
      compared to those with the lepromatous form. The presence of a larger number of
      these cells in patients with the tuberculoid form suggests an important
      participation of langerin-positive cells, capturing antigens and favoring an
      effective immune response to infection with M. leprae.

PMID- 30118800
TI  - Peptides as adjuvants for ampicillin and oxacillin against methicillin-resistant
      Staphylococcus aureus (MRSA).
AB  - Fast emerging antibiotic resistance in pathogens requires special attention for
      strengthening the reservoir of antimicrobial compounds. In view of this, several
      peptides with known antimicrobial activities have been reported to enhance the
      efficacy of antibiotics against multidrug resistant (MDR) pathogens. In the
      present study, potential of peptides having distinct mechanism of action, if any,
      was evaluated to improve the efficacy of conventional antibiotics against
      methicillin-resistant S. aureus (MRSA). After primary screening of six peptides,
      two peptides namely T3 and T4 showing very high minimum inhibitory concentrations
      (MICs) were selected to assess their role in altering the MICs of antibiotics to
      which the pathogen was resistant. In the presence of the peptides, the MICs of
      the antibiotics were found to be reduced as per the fractional inhibitory
      concentration indices (FICI) and time kill assay. These observations prompted us
      to look for their mechanism of action. The effect of peptides on the morphology
      of pathogen by field emission scanning electron microscopy (FE-SEM) revealed no
      damage to the cells at the sub-inhibitory concentrations of the peptide which
      correlated well with the higher MIC of the peptide, indicating no direct impact
      on the pathogen. However, dielectric spectroscopy, confocal microscopy and flow
      cytometry confirmed the interaction and localization of peptides with the
      bacterial membrane. The peptides were also found to inhibit efflux of ethidium
      bromide which is the substrate for many proteins involved in efflux system.
      Therefore, it is speculated that the peptides after interacting with the membrane
      of the pathogen might have resulted in the inhibition of the efflux of
      antibiotics thereby reducing their effective concentrations. The study thus
      suggests that peptides with no antimicrobial activity of their own, can also
      enhance the efficacy of the antibiotics by interacting with the pathogen thereby,
      acting as adjuvants for the antibiotics.

PMID- 30118801
TI  - Moonlighting proteins induce protection in a mouse model against Candida species.
AB  - In recent years, C. albicans and C. glabrata have been identified as the main
      cause of candidemia and invasive candidiasis in hospitalized and
      immunocompromised patients. In order to colonize the human host, these fungi
      express several virulence factors such as the response to oxidative stress and
      the formation of biofilms. In the expression of these virulence factors, the cell
      wall of C. albicans and C. glabrata is of fundamental importance. As the
      outermost structure of the yeast, the cell wall is the first to come in contact
      with the reactive oxygen species (ROS) generated during the respiratory outbreak,
      and in the formation of biofilms, it is the first to adhere to organs or medical
      devices implanted in the human host. In both processes, several cell wall
      proteins (CWP) are required, since they promote attachment to human cells or
      abiotic surfaces, as well as to detoxify ROS. In our working group we have
      identified moonlighting CWP in response to oxidative stress as well as in the
      formation of biofilms. Having identified moonlighting CWP in Candida species in
      response to two virulence factors indicates that these proteins may possibly be
      immunodominant. The aim of the present work was to evaluate whether proteins of
      this type such as fructose-bisphosphate aldolase (Fba1), phosphoglycerate kinase
      (Pgk) and pyruvate kinase (Pk), could confer protection in a mouse model against
      C. albicans and C. glabrata. For this, recombinant proteins His6-Fba1, His6-Pgk
      and His6-Pk were constructed and used to immunize several groups of mice. The
      immunized mice were infected with C. albicans or C. glabrata, and subsequently
      the liver, spleen and kidney were extracted and the number of CFU was determined.
      Our results showed that Pk confers immunity to mice against C. albicans, while
      Fba1 to C. glabrata. This data allows us to conclude that the moonlighting CWP,
      Fba1 and Pk confer in vivo protection in a specific way against each species of
      Candida. This makes them promising candidates for developing specific vaccines
      against these pathogens.

PMID- 30118802
TI  - Edwardsiella piscicida virulence effector trxlp promotes the NLRC4 inflammasome
      activation during infection.
AB  - Edwardsiella piscicida is an important pathogenic bacterium that causes
      hemorrhagic septicemia in fish. This bacterium could activate NLRC4 and NLRP3
      inflammasomes via type III secretion system (T3SS), and inhibit NLRP3
      inflammasome via type VI secretion system (T6SS) effector during infection in
      macrophages. However, the roles of other virulence factors in regulating
      inflammasome activation during E. piscicida infection remain poorly understood.
      In this study, we focused on clarification the role of ETAE_RS10155, a
      thioredoxin-like protein (Trxlp), during bacterial infection in macrophages. We
      found that mutation of this gene barely influences the bacteria growth and
      infection capability. Interestingly, the inflammasome activation was reduced in
      Deltatrxlp-infected macrophages, compared with wild-type E. piscicida did.
      Moreover, Trxlp mainly promotes the NLRC4, but not NLRP3 inflammasome activation
      during E. piscicida infection. Finally, Trxlp-mediated NLRC4 inflammasome
      activation is crucial for host surveillance in vivo. Taken together, our results
      clarify the complex and contextual role of bacterial virulence effector in
      modulating inflammasome activation, and offer new insights into the warfare
      between the fish bacterial weapons and host innate immunological surveillance.

PMID- 30118803
TI  - Ferulic acid derivative inhibits NorA efflux and in combination with
      ciprofloxacin curtails growth of MRSA in vitro and in vivo.
AB  - A series of ferulic acid (FA) derivatives were synthesized and evaluated for its
      ability to inhibit NorA efflux in methicillin resistant Staphylococcus aureus
      (MRSA), by in silico docking analysis. Based on prediction from glide scores and
      ability to reduce EtBr MIC, two of the ten derivatives S3- [4-((E)-2
      (diethylcarbamoyl)vinyl)-2-methoxyphenyl acetate] and S6- [(E)-methyl 3-(4-((p
      tolylcarbamoyl)methoxy)-3-methoxyphenyl)acrylate] were chosen as putative efflux
      pump inhibitors (EPI's). Time dependent accumulation studies revealed that S6
      caused enhanced EtBr accumulation relative to standard NorA efflux inhibitor
      reserpine, in clinical isolate of MRSA (CIMRSA) and in NorA overexpressed strain
      of S. aureus (SA1199B). S6 also exhibited synergy with Ciprofloxacin (CPX)
      against NorA overexpressed strain (SA1199B) of S. aureus but not in NorA knock
      out strain (K1758). MIC reversal studies showed that S3 in CIMRSA and S6 in NorA
      overexpressed strain of S. aureus (SA1199B), caused a 4 fold reduction in CPX
      MIC. In vitro time kill studies revealed that both S3 and S6 with sub MIC of CPX
      caused a significant 4 log CFU decline in CIMRSA. A decline of >3 log fold CFU by
      time kill assay implies synergy between FA derivatives and CPX. When tested in
      vivo in infected muscle tissue of zebrafish both S3 and S6 with CPX caused >3.2
      log decline in CIMRSA cell counts relative to CPX treatment alone. Of the two
      potent derivatives, S6 probably acts through NorA whereas S3 might exert its
      effect through pump other than NorA. Greater in vitro and in vivo efficiency of
      FA derivatives implies its potential to be used as an adjuvant along with CPX to
      curtail MRSA infection in higher animal models.

PMID- 30118804
TI  - Porphyromonas gingivalis induces exacerbated periodontal disease during
      pregnancy.
AB  - Although pregnant women are prone to gingival inflammation, its mechanism remains
      unclear. Animal models are ideal for investigating immunological mechanisms in
      the periodontal disease. A murine model for ligature-induced periodontal disease
      has been modified and utilized to determine the susceptibility to periodontal
      inflammation and tissue damage in pregnant mice. Expression of different
      inflammatory mediators in the gingivae was determined by quantitative real-time
      PCR (qPCR). Inflammatory bone loss was determined by measuring the distance from
      the cementoenamel junction to the alveolar bone crest (CEJ-ABC). Oral bacterial
      number was determined by the CFU (Colony Forming Units) count from anaerobic
      culture of oral swabs. In our experiments, ligation itself did not cause higher
      gingival inflammation and bone loss in pregnant mice than non-pregnant mice,
      while ligation combined with P. gingivalis infection led to increased gingival
      inflammation and periodontal bone loss, accompanied by lower gingival expression
      of anti-inflammatory cytokines in pregnant mice. Our results indicated that P.
      gingivalis infection was important in inducing more severe periodontal diseases
      during pregnancy, which might be attributed to the down-regulated anti
      inflammatory mechanisms, but not be associated with higher oral bacterial burden.

PMID- 30118805
TI  - Biofilm formation in erythromycin-resistant Staphylococcus aureus and the
      relationship with antimicrobial susceptibility and molecular characteristics.
AB  - PURPOSE: In this study, we aimed to investigate biofilm formation characteristics
      in clinical Staphylococcus aureus (S. aureus) isolates with erythromycin (ERY)
      resistance from China and further analyze their correlations with antimicrobial
      susceptibility and molecular characteristics. METHODOLOGY: A total of 276
      clinical isolates of ERY-resistant S. aureus, including 142 methicillin-resistant
      S. aureus (MRSA) strains and 134 methicillin-susceptible S. aureus (MSSA)
      strains, were retrospectively collected in China. Biofilms were determined by
      crystal violet staining and ERY resistance genes (ermA, ermB and ermC) were
      detected by polymerase chain reaction. Inducible clindamycin resistance was
      examined by D test and multilocus sequence typing, and clonal complexes (CCs)
      based on housekeeping genes were further determined. RESULTS: The frequency of
      biofilm formation among ERY-resistant S. aureus was 40.9% (113/276) in total and
      no significant difference was found for the frequency of biofilm formation
      between ERY-resistant MRSA and ERY-resistant MSSA (44.4% vs 37.3%, P > 0.05). In
      ERY-resistant MRSA isolates, the frequency of biofilm formation in ermA-positive,
      gentamicin-resistant and ciprofloxacin-resistant isolates was higher than that in
      ermA-negative, gentamicin-sensitive and ciprofloxacin-sensitive isolates,
      respectively (63.9% vs 23.6%, P < 0.01; 60.3% vs 27.5%, P < 0.01; 65.2% vs 26.3%,
      P < 0.01). In addition, tetracycline resistance facilitated biofilm formation in
      both ERY-resistant MRSA and MSSA and the frequency of biofilm formation in CC239-
      or CC7S. aureus isolates with ERY resistance was significantly higher compared
      with that in CC59S. aureus (both P < 0.01). CONCLUSION: The ermA gene, and
      gentamicin, ciprofloxacin and tetracycline resistance facilitate biofilm
      formation in ERY-resistant MRSA isolates and, moreover, ERY-resistant S. aureus
      isolates with positive biofilm formation exhibited clonality clustering regarding
      CC239 and CC7.

PMID- 30118806
TI  - Chemical composition, cytotoxic effect and antimicrobial activity of Stachys
      koelzii Rech.f. essential oil against periodontal pathogen Prevotella intermedia.
AB  - Prevotella intermedia is associated with periodontal diseases and endodontic
      infections. Periodontitis can be suppressed by utilizing the antiseptics, which
      target the infectious bacteria. The member of Stachys sp. has been used
      traditionally in the form of decoction or infusion for management of infectious
      diseases. The subject of this article was to evaluate the chemical composition,
      antimicrobial and cytotoxic effect of Stachys koelzii essential oil and its main
      components against Prevotella intermedia. GC-FID and GC-MS analysis were used to
      determine the chemical composition. The antimicrobial effects of S. koelzii
      essential oil was evaluated by micro-broth dilution assay. Time kill curve
      assays, leakage of cytoplasmic materials and anti-biofilm effects were
      determined. Its cytotoxic effect was evaluated by MTT assay. Essential oil with
      main components of alpha-pinene, trans-caryophyllene and 1,8-cineole inhibited P.
      intermedia with MIC and MBC values of 0.1 and 0.2 mg/mL. Its biofilm formation
      was higher than alpha-pinene, followed by trans-caryophyllene and 1,8-cineole.
      Essential oil and its main components increased the leakage of cytoplasmic
      components. Essential oil showed cytotoxic effect on HeLa cell lines with IC50
      0.06 mg/mL. The cytotoxic effect of alpha-pinene on healthy cell lines was higher
      than essential oil. S. koelzii essential oil can be used in mouthwash
      formulations and its efficacy should be evaluated in large clinical studies.

PMID- 30118807
TI  - Screening, cloning and expression of a novel alginate lyase gene from P.
      aeruginosa TAG 48 and its antibiofilm effects on P. aeruginosa biofilm.
AB  - BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen and utilizes
      several virulence factors for pathogenesis. One of the most important factors is
      alginate, found in the biofilm which enables P. aeruginosa to establish chronic
      lung infections. MATERIALS AND METHODS: In this study, 25 clinical alginate
      degrading isolates were selected. Biochemical and molecular approach were carried
      out to identify the isolates by 16S rDNA gene amplification. Growth conditions
      and enzyme production were the criteria for selection. Since the main objective
      of the project was the production and characterization of alginate lyase and its
      effect on biofilm elimination, the P. aeruginosa sp.TAG48 alginate lyase-encoding
      gene was isolated, cloned, sequenced and expressed in E.coli DH5alpha. The
      resultant enzyme was purified by affinity chromatography. Ciprofloxacin,
      tobramycin and cefixime were also used to test the effectiveness of these
      antibiotics on P. aeruginosa biofilm by minimum biofilm inhibitory concentration
      (MBIC) and minimum biofilm eradication concentration (MBEC). The synergistic
      effects of these antibiotics and the recombinant alginate lyase on biofilm were
      evaluated. RESULTS: Results indicate that the addition of alginate (0.2%-0.8%)
      and NaCl (0.2-0.5 M) to the medium significantly increases cell growth followed
      by higher enzyme production (p<= 0.05). Moreover, substrate specificity of
      alginate lyase produced by P. aeruginosa sp.TAG48 shows the enzyme is capable of
      degrading both polyM and polyG alginate and acts bifunctionally. Results from the
      antimicrobial characteristics of the antibiotics and the enzyme have shown MBIC
      for ciprofloxacin, tobramycin, cefixime and enzyme in the following
      concentrations 4, 32, 256 and 18.75 MUg/ml, and MBEC: 32, 128, >= 512 and 37.5
      MUg/ml, respectively. The study of synergism between the antibiotics and the
      enzyme to prevent growth and eradication of P. aeruginosa sp.TAG48 biofilm shows
      that alginate lyase exhibits synergy with tobramycin and cefixime but not with
      ciprofloxacin. CONCLUSION: The results indicate that the use of purified novel
      alginate lyase with antibiotics could be a beneficial alternative for the
      treatment of P. aeruginosa infections. Elucidation of mechanisms involved in
      antibiotic resistance and the role of biofilm structure could assist physicians
      select optimum treatment regimen.

PMID- 30118809
TI  - Piece de Self-Resistance: a New Paradigm for Natural-Product Herbicide Discovery.

PMID- 30118810
TI  - Adenine Methylation: New Epigenetic Marker of DNA and mRNA.

PMID- 30118808
TI  - Inorganic nitrate supplementation enhances functional capacity and lower-limb
      microvascular reactivity in patients with peripheral artery disease.
AB  - Peripheral artery disease (PAD) is characterized by functional and vascular
      impairments as well as elevated levels of inflammation which are associated with
      reduced nitric oxide (NO) bioavailability. Inorganic nitrate supplementation
      boosts NO bioavailability potentially improving functional and vasodilatory
      capacities and may reduce inflammation. Twenty-one patients with PAD were
      randomly assigned to sodium nitrate (NaNO3) or placebo supplementation groups for
      eight-weeks. Outcome measures included a 6-min walk test (6 MWT), blood flow and
      vasodilator function in the forearm and calf, as well as plasma inflammatory and
      adhesion biomarker concentrations. NaNO3 elevated plasma nitrate (32.3 +/- 20.0
      to 379.8 +/- 204.6 MUM) and nitrite (192.2 +/- 51.8 to 353.1 +/- 134.2 nM),
      improved 6 MWT performance (387 +/- 90 to 425 +/- 82 m), peak calf blood flow
      (BFPeak; 11.6 +/- 4.9 to 14.1 +/- 5.1 mL/dL tissue/min), and peak calf vascular
      conductance (VCPeak; 11.1 +/- 4.3 to 14.2 +/- 4.9 mL/dL tissue/min/mmHg) (p <
      0.05 for all). Improvements in calf BFPeak (r = 0.70, p < 0.05) and VCPeak (r =
      0.61, p < 0.05) correlated with changes in 6 MWT distance. Placebo
      supplementation did not change plasma nitrate or nitrite, 6 MWT, calf BFPeak, or
      calf VCPeak. Forearm vascular function nor inflammatory and adhesion biomarker
      concentrations changed in either group. Eight-weeks of NaNO3 supplementation
      improves vasodilatory capacity in the lower-limbs of patients with PAD, which
      correlated with improvement in functional capacity.

PMID- 30118811
TI  - Breaking the frontiers of cosmetology with antimicrobial peptides.
AB  - Antimicrobial peptides (AMPs) are mostly endogenous, cationic, amphipathic
      polypeptides, produced by many natural sources. Recently, many biological
      functions beyond antimicrobial activity have been attributed to AMPs, and some of
      these have attracted the attention of the cosmetics industry. AMPs have revealed
      antioxidant, self-renewal and pro-collagen effects, which are desirable in anti
      aging cosmetics. Additionally, AMPs may also be customized to act on specific
      cellular targets. Here, we review the recent literature that highlights the many
      possibilities presented by AMPs, focusing on the relevance and impact that this
      potentially novel class of active cosmetic ingredients might have in the near
      future, creating new market outlooks for the cosmetic industry with these
      molecules as a viable alternative to conventional cosmetics.

PMID- 30118813
TI  - In search of a needle.

PMID- 30118812
TI  - End-tidal carbon dioxide during pediatric in-hospital cardiopulmonary
      resuscitation.
AB  - BACKGROUND: Based on laboratory cardiopulmonary resuscitation (CPR)
      investigations and limited adult data, the American Heart Association Consensus
      Statement on CPR Quality recommends titrating CPR performance to achieve end
      tidal carbon dioxide (ETCO2) >20 mmHg. AIMS: We prospectively evaluated whether
      ETCO2 > 20 mmHg during CPR was associated with survival to hospital discharge.
      METHODS: Children >=37 weeks gestation in Collaborative Pediatric Critical Care
      Research Network intensive care units with chest compressions for >=1 min and
      ETCO2 monitoring prior to and during CPR between July 1, 2013 and June 31, 2016
      were included. ETCO2 and Utstein-style cardiac arrest data were collected.
      Multivariable Poisson regression models with robust error estimates were used to
      estimate relative risk of outcomes. RESULTS: Blinded investigators analyzed ETCO2
      waveforms from 43 children. During CPR, the median ETCO2 was 23 mmHg [quartiles,
      16 and 28 mmHg], median ventilation rate was 29 breaths/min [quartiles, 24 and 35
      breaths/min], and median duration of CPR was 5 min [quartiles, 2 and 16 min].
      Return of spontaneous circulation occurred after 71% of CPR events and 37% of
      patients survived to hospital discharge. For children with mean ETCO2 during CPR
      > 20 mmHg, the adjusted relative risk for survival was 0.92 (0.41, 2.08), p =
      0.84. The median mean ETCO2 among children who survived to hospital discharge was
      20 mmHg [quartiles; 15, 28 mmHg] versus 23 mmHg [16, 28 mmHg] among non
      survivors. CONCLUSION: Mean ETCO2 > 20 mmHg during pediatric in-hospital CPR was
      not associated with survival to hospital discharge, and ETCO2 was not different
      in survivors versus non-survivors.

PMID- 30118814
TI  - Timing and modes of death after pediatric out-of-hospital cardiac arrest
      resuscitation.
AB  - AIM: To determine the timing and modes of death of children admitted to a
      pediatric critical care unit (PICU) of a tertiary care center after an out-of
      hospital cardiac arrest (OHCA). METHODS: This is a retrospective descriptive
      study at a tertiary care PICU of all consecutive patients <18 years old who
      received >=1 min of chest compressions, had return of spontaneous circulation
      (ROSC) for >=20 min, and were admitted to the PICU after an OHCA. Modes of death
      were classified as brain death (BD), withdrawal due to neurologic prognosis (W/D
      neuro), withdrawal for refractory circulatory failure (W/D-RCF), and re-arrest
      without ROSC (RA). RESULTS: 191 consecutive patients were admitted to the PICU
      from February 2005 to May 2013 after an OHCA. Eighty-six(45%) patients died prior
      to discharge: BD in 47%(40/86), W/D-neuro in 34%(29/86), W/D-RCF in 10%(9/86),
      and RA in 9%(8/86). Time to death was longer for patients with W/D-neuro: 4 days
      [1, 5] and BD 4 days [1, 5](p < 0.01) as opposed to those with W/D-RCF (1 day[1,
      2]) and RA(1 day[0.5, 1]). Of patients who underwent W/D-neuro, 9/29(31%) died
      within 3 days of PICU admission and 20/29(69%) >=3 days. Of patients who died
      after W/D-neuro, 12/29(41%) received therapeutic hypothermia, 27/29(93%)
      underwent EEG monitoring, 21/29(72%) had a brain CT, and 13/29(45%) had a brain
      MRI. All MRIs showed signs of hypoxic-ischemic injury. CONCLUSION: Neurologic
      injury was the most common mode of death post-resuscitation care OHCA after in a
      tertiary care center PICU. Neurologic prognostication impacts the outcome of a
      large proportion of patients after OHCA, and further studies are warranted to
      improve its reliability.

PMID- 30118815
TI  - Identification of zebrafish steroid sulfatase and comparative analysis of the
      enzymatic properties with human steroid sulfatase.
AB  - Steroid sulfatase (STS) plays an important role in the regulation of steroid
      hormones. Metabolism of steroid hormones in zebrafish has been investigated, but
      the action of steroid sulfatase remains unknown. In this study, a zebrafish sts
      was cloned, expressed, purified, and characterized in comparison with the
      orthologous human enzyme. Enzymatic assays demonstrated that similar to human
      STS, zebrafish Sts was most active in catalyzing the hydrolysis of estrone
      sulfate and estradiol-sulfate, among five steroid sulfates tested as substrates.
      Kinetic analyses revealed that the Km values of zebrafish Sts and human STS
      differed with respective substrates, but the catalytic efficiency as reflected by
      the Vmax/Km appeared comparable, except for DHEA-sulfate with which zebrafish Sts
      appeared less efficient. While zebrafish Sts was catalytically active at 28 
      degrees C, the enzyme appeared more active at 37  degrees C and with similar Km
      values to those determined at 28  degrees C. Assays performed in the presence of
      different divalent cations showed that the activities of both zebrafish and human
      STSs were stimulated by Ca2+, Mg2+, and Mn2+, and inhibited by Zn+2 and Fe2+.
      EMATE and STX64, two known mammalian steroid sulafatase inhibitors, were shown to
      be capable of inhibiting the activity of zebrafish Sts. Collectively, the results
      obtained indicated that zebrafish Sts exhibited enzymatic characteristics
      comparable to the human STS, suggesting that the physiological function of STS
      may be conserved between zebrafish and humans.

PMID- 30118816
TI  - Single transcript imaging to assay gene expression in wholemount Drosophila
      melanogaster tissues.
AB  - Single molecule Fluorescence in situ Hybridization (smFISH) for mRNA provides a
      powerful quantitative handle on expression from endogenous gene loci. While the
      method has been widely applied in cells in culture, applications to primary
      tissue samples remain fewer, and often use involved cryosectioning. Even apart
      from quantitative access to absolute transcript counts in specific tissue
      volumes, many other advantages of smFISH can be envisaged in tissue samples.
      Primary among these are the ability to report on subtle differences in expression
      among different cell types within a tissue, and the ability to correlate the
      expression from different target genes. Here, we present a modified method of
      smFISH applicable on various primary wholemount tissues from the fruit fly
      Drosophila melanogaster, and show the efficacy of the method in a variety of
      larval and adult tissue, and embryos. We also combine smFISH in tissue with
      immunofluorescence to demonstrate the possibility of capturing transcriptional
      and translational aspects of gene expression in the same tissue. Given the
      widespread use of Drosophila melanogaster as a model system in Developmental
      Biology and Genetics, such methods are likely to be of wide interest and could
      yield rich information about gene expression in tissues from this organism.

PMID- 30118817
TI  - Conformational flexibility of pore loop-1 gives insights into substrate
      translocation by the AAA+ protease FtsH.
AB  - Two crystal structures of a transmembrane helix-lacking FtsH construct from
      Aquifex aeolicus have been determined at 2.9 A and 3.3 A resolution in space
      groups R32 and P312, respectively. Both structures are virtually identical
      despite different crystal packing contacts. In both structures, the FtsH hexamer
      is created from two different subunits of the asymmetric unit by the threefold
      symmetry of the crystals. Similar to other published structures, all subunits are
      loaded with ADP and the two subunit in the asymmetric unit resemble the already
      known open and closed conformations. Within the ATPase cycle while the whole
      subunit switches from the opened to the closed state, pore loop-1 interacts with
      the substrate and translocates it into the proteolytic chamber. Unique to our
      models is a presumably inactive conformation of the pore loop which allows the
      closed conformation to switch back to the opened state without pushing the
      substrate out again. Our structures give further insights on how this new pore
      loop conformation is induced and how it is linked to the intersubunit signalling
      network.

PMID- 30118818
TI  - RIFM fragrance ingredient safety assessment, 3a,4,5,6,7,7a-hexahydro-4,7-methano
      1H-inden-5-yl isobutyrate, CAS registry number 67634-20-2.

PMID- 30118819
TI  - RIFM fragrance ingredient safety assessment, 2-butanone, phenylhydrazone, CAS
      Registry Number 1129-62-0.

PMID- 30118820
TI  - Assessing the mycotoxicological risk from consumption of complementary foods by
      infants and young children in Nigeria.
AB  - This study assessed, for the first time, the mycotoxicological risks from
      consumption of complementary foods by infants and young children in Nigeria.
      Molds belonging to Aspergillus aculeatinus, A. flavus, A. luchuensis, A.
      tubingensis, A. welwitschiae and Geotrichum candidum were recovered from the
      complementary foods. Twenty-eight major mycotoxins and derivatives, and another
      109 microbial metabolites including chloramphenicol (a bacterial metabolite),
      were quantified in 137 food samples by LC-MS/MS. Aflatoxins and fumonisins co
      contaminated 42% of the cereal- and nut-based food samples, at mean
      concentrations exceeding the EU limits of 0.1 and 200 MUg/kg set for processed
      baby foods by 300 and six times, respectively. Milk contained mainly beauvericin,
      chloramphenicol and zearalenone. The trichothecenes, T-2 and HT-2 toxins, were
      quantified only in infant formula and at levels three times above the EU
      indicative level of 15 MUg/kg for baby food. Chronic exposure estimate to
      carcinogenic aflatoxin was high causing low margin of exposure (MOE). Exposures
      to other mycotoxins either exceeded the established reference values by several
      fold or revealed low MOEs, pointing to important health risks in this highly
      vulnerable population. The observed mycotoxin mixtures may further increase risks
      of adverse health outcomes of exposure; this warrants urgent advocacy and
      regulatory interventions.

PMID- 30118821
TI  - RIFM fragrance ingredient safety assessment, geranic acid, CAS Registry Number
      459-80-3.

PMID- 30118822
TI  - FDG/PET-CT-Based Lymph Node Atlas in Breast Cancer Patients.
AB  - PURPOSE: The aim of this study was to localize locoregional lymph node metastases
      using positron emission tomography with fluorine 18-fluorodeoxyglucose positron
      emission tomography/computed tomography (FDG-PET/CT) data sets in a large cohort
      of patients and to evaluate the existing Radiation Therapy Oncology Group (RTOG)
      clinical target volume (CTV) and the European Society for Radiation Therapy &
      Oncology (ESTRO) CTV contouring guidelines. METHODS AND MATERIALS: A total of 235
      patients with 580 FDG/PET-CT positive locoregional lymph node metastases were
      included in our analysis. The patients were divided into 4 groups according to
      their course of disease (primary vs recurrent breast cancer) and the presence or
      absence of distant metastasis at the time of the FDG-PET/CT staging (distant
      metastasis vs no distant metastasis). All imaging data were imported into the
      planning system, and each lymph node was manually contoured. A patient with
      "standard anatomy" was chosen as a template, and all contoured structures were
      registered rigidly and nonrigidly to this patient. A comprehensive 3-dimensional
      atlas was created, including all identified lymph node metastases. The incidences
      of lymph node metastases were analyzed and are presented with color coding in the
      atlas. Lymph node levels (axillary, internal mammary, supraclavicular) were
      contoured according to RTOG and ESTRO guidelines and evaluated. RESULTS: The mean
      volume of the lymph nodes was 1.7 +/- 2.6 cm3 with an average diameter of 1.3 +/-
      0.7 cm. Most lymph nodes were in level I (n = 316; 54.5%) followed by the
      supraclavicular region (n = 80; 13.8%), level II (n = 57; 9.8%), level III (n =
      58; 10.0%), and the internal mammary region (n = 55; 9.5%). The covered lymph
      node volume was 69.8% +/- 35.5% (69.1% +/- 36.3%) for primary breast cancer and
      57.6% +/- 38.9% (51.1% +/- 39.1%) for recurrent breast cancer using the RTOG
      (ESTRO) guidelines. The internal mammary region and supraclavicular region were
      affected more often in recurrent breast cancer compared with primary breast
      cancer. The occurrence of lymph node metastases outside the RTOG and ESTRO
      margins in patients with and without distant metastases was similar. The largest
      geometric deviations between RTOG/ESTRO CTV contours and lymph node occurrence
      were measured in the supraclavicular region, the internal mammary region, and
      level II. CONCLUSIONS: The provided lymph node atlas illustrates where lymph node
      metastases occur in different clinical situations and presents areas at high risk
      (ie "hot spots" of lymph node metastases).

PMID- 30118823
TI  - The opioid system in stress-induced memory disorders: From basic mechanisms to
      clinical implications in post-traumatic stress disorder and Alzheimer's disease.
AB  - Cognitive and emotional impairment are a serious consequence of stress exposure
      and are core features of neurological and psychiatric conditions that involve
      memory disorders. Indeed, acute and chronic stress are high-risk factors for the
      onset of post-traumatic stress disorder (PTSD) and Alzheimer's disease (AD), two
      devastating brain disorders associated with memory dysfunction. Besides the
      sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis,
      stress response also involves the activation of the opioid system in brain
      regions associated with stress regulation and memory processing. In this context,
      it is possible that stress-induced memory disorders may be attributed to
      alterations in the interaction between the neuroendocrine stress system and the
      opioid system. In this review, we: (1) describe the effects of acute and chronic
      stress on memory, and the modulatory role of the opioid system, (2) discuss the
      contribution of the opioid system to the pathophysiology of PTSD and AD, and (3)
      present evidence of current and potential therapies that target the opioid
      receptors to treat PTSD- and AD-associated symptoms.

PMID- 30118824
TI  - The interaction between the ZNF804A gene and cannabis use on the risk of
      psychosis in a non-clinical sample.
AB  - The ZNF804A gene and cannabis use are risk factors for psychosis and both have
      also been associated with schizotypal traits. This study aimed to investigate: i)
      the association of lifetime cannabis use (and its dose effect) with schizotypal
      personality traits, and ii) whether the genetic variability at ZNF804A gene
      modulates that association. Our sample consisted of 385 Spanish non-clinical
      subjects (43.1% males, mean age = 21.11(2.19)). Schizotypy was evaluated using
      the three factors of the Schizotypal Personality Questionnaire-Brief (SPQ-B):
      Cognitive-Perceptual (SPQ-CP), Interpersonal (SPQ-I) and Disorganized (SPQ-D).
      Subjects were classified according to their frequency of cannabis consumption,
      and dichotomized as users or non-users. The effects of a genetic variant of
      ZNF804A (rs1344706) and cannabis use, as well as their interaction, on each of
      the three SPQ-B factors were assessed using linear models and permutation tests.
      Sex, SCL anxiety scores and use of other drugs were included as covariates. Our
      analysis showed a significant relationship between ZNF804A and SPQ-I: AA genotype
      was associated with higher scores (beta = 0.885 pFDR = .018). An interaction
      between the AA genotype and lifetime cannabis use was found in SPQ-CP (beta =
      1.297 pFDR = 0.018). This interaction showed a dose-effect pattern among AA
      subjects: schizotypy scores increased with increasing frequency of cannabis use
      (sporadic users: beta = 0.746 pFDR = 0.208; monthly users: beta = 1.688 pFDR =
      0.091; intense users: beta = 1.623 pFDR = 0.038). These results add evidence on
      that the ZNF804A gene is associated with schizotypy and suggest that the
      interaction between cannabis use and ZNF804A genotype could modulate psychosis
      proneness.

PMID- 30118825
TI  - Cortical thickness in major depressive disorder: A systematic review and meta
      analysis.
AB  - Neuroimaging studies assessing neurobiological differences between patients with
      major depressive disorder (MDD) and healthy controls (HC) are often hindered by
      small sample sizes and heterogeneity of the patient sample. We performed a
      comprehensive literature search for studies assessing cortical thickness between
      patient and control groups, including studies investigating treatment effects on
      cortical thickness. We identified 34 studies meeting criteria for the systematic
      review and used Seed-based d Mapping to meta-analyze 24 of those that met
      additional criteria. Analysis of the full sample of subjects (MDD = 1073; HC =
      936) revealed significant thinning in the MDD group in the bilateral
      orbitofrontal gyrus (BA 11), left pars opercularis (BA 45) and left calcarine
      fissure/lingual gyrus (BA 17), as well as an area of significant thickening in
      the left supramarginal gyrus (BA 40). These results support other imaging
      modalities that report disruptions in various frontal and temporal areas in MDD
      and identify additional areas in all major cerebral lobes likely to be
      significant when parsing for biomarkers of treatment or relapse.

PMID- 30118826
TI  - 7.0 tesla high resolution MRI study on intracerebral migration of magnet-labeled
      neural stem cells in a mouse model of Alzheimer's disease.
AB  - OBJECTIVE: To observe the migration characteristics of neural stem cells (NSCs)
      labeled with the MRI contrast agent superparamagnetic iron oxide (SPIO) in the
      brain of APP/PS1 transgenic mice with Alzheimer's disease (AD) by 7.0 T high
      resolution MRI. METHODS: C57BL/6 mouse NSCs were cultured, amplified, labeled
      with Feridex and Poly-l-lysine (FE-PLL) and evaluated by transmission electron
      microscopy (TEM). Using the random number table method, 24 APP/PS1 transgenic AD
      mice aged 12 months were equally assigned to two groups: animals in group A were
      transplanted with FE-PLL labeled NSCs and those in group B were transplanted with
      non-labeled NSCs in the right hippocampus. Twelve wild-type mice of the same age
      and born from the same litter were used as the control group (group C) and
      transplanted with FE-PLL labeled NSCs. Using the 7.0 T high resolution MR
      scanner, the transplanted NSCs were traced in vivo at 1 day, 1 and 2 weeks after
      cell transplantation. The MRI findings were compared with the histopathological
      findings. RESULTS: C57BL/6 mouse NSCs were cultured and amplified successfully.
      TEM showed large amounts of iron-containing particles in the cytoplasm of
      transplanted cells. MRI in group A showed the presence of spheroid low signals at
      the injection point of the hippocampus on T2*WI one day after transplantation;
      one weeks later, the low signals were seen diffusing to the surroundings along
      the injection point, and covering almost the whole hippocampal area but the
      intensity of the low signals became weaker gradually; two weeks after
      transplantation, almost all low signals disappeared. In group B, no significant
      change in low signals was observed in the transplantation area at all designated
      time points. Although low signals were also observed in the hippocampus after
      transplantation of FE-PLL labeled NSCs in group C, their size and location
      remained almost unchanged. Prussian blue staining showed that migration of the FE
      PLL labeled NSCs in the hippocampus of the AD mice was consistent with the MRI
      findings at all designated time points. CONCLUSION: NSCs underwent diffuse and
      non-directional migration to the surroundings after they were transplanted to the
      hippocampus of APP/PS1 transgenic AD mice, and this migration pattern could be
      traced in vivo by MRI when they were labeled with magnet.

PMID- 30118827
TI  - Left ventricular MRI wall motion assessment by monogenic signal amplitude image
      computation.
AB  - BACKGROUND: Cardiac Magnetic Resonance Imaging (MRI) is the commonly used
      technique for the assessment of left ventricular (LV) function. Apart manually or
      semi-automatically contouring LV boundaries for quantification of By visual
      interpretation of cine images, assessment of regional wall motion is performed by
      visual interpretation of cine images, thus relying on an experience-dependent and
      subjective modality. OBJECTIVE: The aim of this work is to describe a novel
      algorithm based on the computation of the monogenic amplitude image to be
      utilized in conjunction with conventional cine-MRI visualization to assess LV
      motion abnormalities and to validate it against gold standard expert visual
      interpretation. METHODS: The proposed method uses a recent image processing tool
      called "monogenic signal" to decompose the MR images into features, which are
      relevant for motion estimation. Wall motion abnormalities are quantified locally
      by measuring the temporal variations of the monogenic signal amplitude. The new
      method was validated by two non-expert radiologists using a wall motion scoring
      without and with the computed image, and compared against the expert
      interpretation. The proposed approach was tested on a population of 40 patients,
      including 8 subjects with normal ventricular function and 32 pathological cases
      (20 with myocardial infarction, 9 with myocarditis, and 3 with dilated
      cardiomyopathy). RESULTS: The results show that, for both radiologists,
      sensitivity, specificity and accuracy of cine-MRI alone were similar and around
      59%, 77%, and 71%, respectively. Adding the proposed amplitude image while
      visualizing the cine MRI images significantly increased both sensitivity,
      specificity and accuracy up to 75%, 89%, and 84%, respectively. CONCLUSION:
      Accuracy of wall motion interpretation adding amplitude image to conventional
      visualization was proven feasible and superior to standard image interpretation
      on the considered population, in inexperienced observers. Adding the amplitude
      images as a diagnostic tool in clinical routine is likely to improve the
      detection of myocardial segments presenting a cardiac dysfunction.

PMID- 30118828
TI  - Phloroglucinol ameliorates cognitive impairments by reducing the amyloid beta
      peptide burden and pro-inflammatory cytokines in the hippocampus of 5XFAD mice.
AB  - Among the various causative factors involved in the pathogenesis of Alzheimer's
      disease (AD), oxidative stress has emerged as an important factor. Phloroglucinol
      is a polyphenol component of phlorotannin, which is found at sufficient levels in
      Ecklonia cava (E. cava). Phloroglucinol has been reported to exert antioxidant
      activities in various tissues. Previously, we reported that the stereotaxic
      injection of phloroglucinol regulated synaptic plasticity in an AD mouse model.
      In this study, we aimed to investigate the effects of oral administration of
      phloroglucinol in AD. The oral administration of phloroglucinol for 2 months
      attenuated the impairments in cognitive function observed in 6-month-old 5X
      familial AD (5XFAD) mice, as assessed with the T-maze and Y-maze tests. The
      administration of phloroglucinol for 2 months in 5XFAD mice caused a reduction in
      the number of amyloid plaques and in the protein level of BACE1, a major amyloid
      precursor protein cleavage enzyme, together with gamma-secretase. Phloroglucinol
      also restored the reduction in dendritic spine density and the number of mature
      spines in the hippocampi of 5XFAD mice. In addition, phloroglucinol-administered
      5XFAD mice displayed lower protein levels of GFAP and Iba-1 and mRNA levels of
      TNF-alpha and IL-6 compared with vehicle-administered 5XFAD mice. These results
      demonstrated that phloroglucinol alleviated the neuropathological features and
      behavioral phenotypes in the 5XFAD mouse model. Taken together, our results
      suggest that phloroglucinol has therapeutic potential for AD treatment.

PMID- 30118829
TI  - Identification of urate hydroperoxide in neutrophils: A novel pro-oxidant
      generated in inflammatory conditions.
AB  - Uric acid is the final product of purine metabolism in humans and is considered
      to be quantitatively the main antioxidant in plasma. In vitro studies showed that
      the oxidation of uric acid by peroxidases, in presence of superoxide, generates
      urate free radical and urate hydroperoxide. Urate hydroperoxide is a strong
      oxidant and might be a relevant intermediate in inflammatory conditions. However,
      the identification of urate hydroperoxide in cells and biological samples has
      been a challenge due to its high reactivity. By using mass spectrometry, we
      undoubtedly demonstrated the formation of urate hydroperoxide and its
      corresponding alcohol, hydroxyisourate during the respiratory burst in peripheral
      blood neutrophils and in human leukemic cells differentiated in neutrophils (dHL
      60). The respiratory burst was induced by phorbol myristate acetate (PMA) and
      greatly increased oxygen consumption and superoxide production. Both oxygen
      consumption and superoxide production were further augmented by incubation with
      uric acid. Conversely, uric acid significantly decreased the levels of HOCl,
      probably because of the competition with chloride by the catalysis of
      myeloperoxidase. In spite of the decrease in HOCl, the overall oxidative status,
      measured by GSH/GSSG ratio, was augmented in the presence of uric acid. In
      summary, the present results support the formation of urate hydroperoxide, a
      novel oxidant in neutrophils oxidative burst. Urate hydroperoxide is a strong
      oxidant and alters the redox balance toward a pro-oxidative environment. The
      production of urate hydroperoxide in inflammatory conditions could explain, at
      least in part, the harmful effect associated to uric acid.

PMID- 30118830
TI  - Role of GPx3 in PPARgamma-induced protection against COPD-associated oxidative
      stress.
AB  - Cigarette smoke, a source of numerous oxidants, produces oxidative stress and
      exaggerated inflammatory responses that lead to irreversible lung tissue damage.
      It is the single, most significant risk factor for chronic obstructive pulmonary
      disease (COPD). Although an intrinsic defense system that includes both enzymatic
      and non-enzymatic modulators exists to protect lung tissues against oxidative
      stress, impairment of these protective mechanisms has been demonstrated in
      smokers and COPD patients. The antioxidant enzyme GSH peroxidase (GPx) is an
      important part of this intrinsic defense system. Although cigarette smoke has
      been shown to downregulate its expression and activity, the underlying mechanism
      is not known. Peroxisome proliferator-activated receptor gamma (PPARgamma) is a
      nuclear hormone receptor with antioxidant effects. PPARgamma activation has
      demonstrated protective effects against cigarette smoke-induced oxidative stress
      and inflammation. Molecular mechanisms for PPARgamma's antioxidant function
      likewise remain to be elucidated. This study explored the link between PPARgamma
      and GPx3 and found a positive association in cigarette smoke extract (CSE)
      exposed human bronchial epithelial cells. Moreover, we provide evidence that
      identifies GPx3 as a PPARgamma transcriptional target. Attenuation of antioxidant
      effects in the absence of GPx3 highlights the antioxidant's prominent role in
      mediating PPARgamma's function. We also demonstrate that ligand-mediated
      PPARgamma activation blocks CSE-induced reactive oxygen species and hydrogen
      peroxide production via upregulation of GPx3. In summary, our findings describing
      the molecular mechanisms involving GPx3 and PPARgamma in CSE-induced oxidative
      stress and inflammation may provide valuable information for the development of
      more effective therapeutics for COPD.

PMID- 30118831
TI  - A multivariate raw material property database to facilitate drug product
      development and enable in-silico design of pharmaceutical dry powder processes.
AB  - In current study a holistic material characterization approach was proposed and
      an extensive raw material property database was developed including a wide
      variety of APIs and excipients with different functionalities. In total 55
      different materials were characterized and described by over 100 raw material
      descriptors related to particle size and shape distribution, specific surface
      area, bulk, tapped and true density, compressibility, electrostatic charge,
      moisture content, hygroscopicity, permeability, flowability and wall friction.
      Principal component analysis (PCA) was applied to reveal similarities and
      dissimilarities between materials and to identify overarching properties. The
      developed PCA model allows to rationalize the number of critical characterization
      techniques in routine characterization and to identify surrogates for use during
      early drug product development stages when limited amounts of active
      pharmaceutical ingredients are available. Additionally, the developed database
      will be the basis to build predictive models for in silico process and
      formulation development based on (a selection of) property descriptors.

PMID- 30118832
TI  - Polymeric nanocapsules as drug carriers for sustained anticancer activity of
      calcitriol in breast cancer cells.
AB  - Clinical use of calcitriol (1,25-dihydroxyvitamin D3) as an anticancer agent is
      currently limited by the requirement of supraphysiological doses and associated
      hypercalcemia. Nanoencapsulation of calcitriol is a strategy to overcome these
      drawbacks, allowing reduced administrated doses and/or frequency, while retaining
      the therapeutic activity towards cancer cells. For this purpose, we investigated
      the impact of calcitriol encapsulation on its antiproliferative activity and
      optimized formulation parameters with that respect. Calcitriol-loaded polymeric
      nanoparticles with different polymer:oil ratios were prepared by the
      nanoprecipitation method. Nanoparticles had similar mean size (200 nm) and EE
      (85%) whereas their release profile strongly depended on formulation parameters.
      Antiproliferative and cytotoxic activities of formulated calcitriol were
      evaluated in vitro using human breast adenocarcinoma cells (MCF-7) and showed
      that calcitriol-induced cell growth inhibition was closely related to its release
      kinetics. For the most suitable formulation, a sustained cell growth inhibition
      was observed over 10 days compared to free form. Advantages of calcitriol
      encapsulation and the role of formulation parameters on its biological activity
      in vitro were demonstrated. Selected nanoparticle formulation is a promising
      calcitriol delivery system ensuring a prolonged anticancer activity that could
      improve its therapeutic efficiency.

PMID- 30118833
TI  - Design and synthesis of biologically active cationic amphiphiles built on the
      calix[4]arene scaffold.
AB  - A promising strategy to design safer and more effective cationic lipids for gene
      delivery with inherent antibacterial properties is to covalently tether a
      lipophilic moiety with oligomeric aminoglycosides (AGs), a large family of Gram
      negative-active antibiotics. Herein, we reported the development of a new class
      of multicationic-head AG-based amphiphiles built on the tetramino
      tetrahexyloxycalix[4]arene (4A4Hex-calix-calix[4]) scaffold. Three different
      conjugates, namely 4A4Hex-calix-calix[4]-neomycin, -neamine, and -paromomycin,
      were synthesized and characterized. Due to the inherent multivalency of AGs and
      the amphiphilic behaviour, every 4A4Hex-calix-calix[4]-AG exhibited greater DNA
      binding ability than the gold standard transfectant 25 kDa bPEI and striking DNA
      packing ability. DNA/4A4Hex-calix-calix[4]-AG complexes at charge ratios (CRs, +/
      ) used for transfections displayed good colloidal stability, with a hydrodynamic
      diameters of ~150 nm and an overall surface charges of ~+30 mV. DNA/4A4Hex
      calix[4]-AGs nanoassemblies, everyone tested at the optimal CR, invariably showed
      good transfection efficiency in two cell lines, along with low-to-negligible
      cytotoxicity. Besides, DNA/4A4Hex-calix-calix[4]-AG complexes exhibited
      appreciable antimicrobial activity against Gram-negative bacteria, even greater
      than uncomplexed 4A4Hex-calix-calix[4]-AGs. Altogether, these results disclose
      4A4Hex-calix[4]-AGs as promising gene delivery tools with unique antibacterial
      properties.

PMID- 30118834
TI  - Effect of Artemisia herba-alba consumption during pregnancy on fertility,
      morphological and behaviors of mice offspring.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Pregnant women prefer herbal medicines more than
      pharmaceutical drugs due to the cultural belief that herbs are more suffer during
      pregnancy for an accurate foetus development. Artemisia herba-alba (Asteraceae)
      is one of the most used plants in the Mediterranean region to treat various
      diseases including diabetes, hypertension, spasmodic dysphonia and some bacterial
      infection. AIM OF THE STUDY: The present study aimed to investigate the effect of
      Artemisia herba-alba consumption during pregnancy on fertility, physical and
      behavior developments of mice offspring from birth-to-weaning days. MATERIALS AND
      METHODS: Female pregnant mice were divided into three groups and orally
      administrated with 80 and 150 mg/kg/day of the methanol extract of Artemisia h.a
      respectively, during the entire period of gestation. At birth, total fertility
      rate was counted. Body development; neuromotor reflex and behavior were also
      examined in mice offspring RESULTS: Artemisia h.a (Aha) exposure significantly
      decreased the fertility ratio in both Aha-treated groups and increased the weight
      and length of mice offspring in 80 mg/kg/day Aha-exposed group. Moreover, Aha
      administration prolonged the time of completing the reflex response of surface
      righting, negative geotaxis, cliff avoidance and jumping test of mice offspring
      in Aha-exposed groups. CONCLUSION: The present study provides strong evidence
      that discourage the use of Artemisia h.a during gestation period.

PMID- 30118835
TI  - Utilization of Chinese herbal medicine and its association with the risk of
      fracture in patients with Parkinson's disease in Taiwan.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used
      for over two thousand years to treat motor impairments corresponding to the
      clinical manifestations of Parkinson's disease (PD). AIM OF THE STUDY: This study
      aimed to investigate the prescription of Chinese herbal medicine (CHM) for the
      management of PD and further determine whether CHM can improve motor function and
      decrease the risk of incident fracture. MATERIALS AND METHODS: Patients older
      than 40 years newly diagnosed with PD between January 1997 and December 2010 were
      selected from the National Health Insurance Research Database (NHIRD) and
      followed up until the end of 2013. We used 1:1 frequency matching by age, sex,
      index year, and initial diagnostic year to compare the TCM users and non-TCM
      users. We used a Cox regression model and the Kaplan-Meier method to estimate the
      risk of developing fracture among the TCM and non-TCM users. RESULTS: In total,
      7197 patients older than 40 years were newly diagnosed with PD between 1997 and
      2010 in Taiwan. Among these patients, 3456 were TCM users, and 3730 were non-TCM
      users. We compared 2007 PD patients with comparable demographic characteristics
      and comorbidity profiles between the two cohorts. During the follow-up period,
      compared with the non-TCM cohort, fewer patients in the TCM cohort had incident
      fractures (adjusted hazard ratio: 0.5, 95% CI: 0.44-0.56). The cumulative
      incidence of fracture was lower in the TCM cohort (log-rank test, p < 0.0001).
      Shi-Chang-Pu (Acorus gramineus Aiton), Yuan-Zhi (Polygala tenuifolia Willd), Bei
      Mu (Fritillaria cirrhosa D. Don), Hai-Piao-Xiao (Sepiella maindronide Rochebrune;
      Sepia esculenta Hoyle), and Tian-Ma (Gastrodia elata Blume) constituted the core
      Chinese herbal medicine prescriptions used to treat PD patients. CONCLUSIONS: The
      present study identified the core prescription pattern for the management of PD
      in Taiwan. Complementary CHM therapy was associated with a reduced risk of
      fracture in PD patients.

PMID- 30118836
TI  - Leptospermum flavescens Sm. protect pancreatic beta cell function from
      streptozotocin involving apoptosis and autophagy signaling pathway in in vitro
      and in vivo case study.
AB  - ETHNOPHARMACOLOGICAL IMPORTANCE: Leptospermum flavescens has been used
      traditionally in Malaysia to treat various ailments such as constipation,
      hypertension, diabetes and cancer. AIM OF STUDY: To investigate the potential
      protective effects of L. flavescens in pancreatic beta cells through inhibition
      of apoptosis and autophagy cell death mechanisms in in vitro and in vivo models.
      MATERIALS AND METHODS: L. flavescens leaves were extracted using solvent in
      increasing polarities: hexane, ethyl acetate, methanol and water. All extracts
      were tested for INS-1 beta cells viability stimulated by streptozotocin (STZ).
      The extract which promotes the highest cell protective activity was further
      evaluated for insulin secretion, apoptosis and autophagy signaling pathways.
      Then, the acute toxicity of extract was carried out in SD rats according to OECD
      423 guideline. The active extract was tested in diabetic rats where the
      pancreatic beta islets were evaluated for insulin, apoptosis and autophagy
      protein. RESULTS: The methanolic extract of L. flavescens (MELF) was found to
      increase INS-1 beta cells viability and insulin secretion against STZ. In
      addition, MELF has been shown to inhibit INS-1 beta cells apoptosis and autophagy
      activity. Notably, there was no toxicity observed in SD rats when administered
      with MELF. Furthermore, MELF exhibited anti-hyperglycemic activity in diabetic
      rats where apoptosis and autophagy protein expression was found to be suppressed
      in pancreatic beta islets. CONCLUSION: MELF was found to protect pancreatic beta
      cells function from STZ-induced apoptosis and autophagy in in vitro and in vivo.

PMID- 30118837
TI  - An ethnobotanical survey and inhibitory effects on NLRP3 inflammasomes/Caspase-1
      of herbal recipes' extracts traditionally used in Rwanda for asthma treatment.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Respiratory diseases and asthma, in particular,
      are nowadays a global health problem. In Rwanda, some traditional healers claim
      to treat asthma with plant-based recipes, though there is no scientific proof so
      far. AIM OF THE STUDY: Our study aimed at evaluating the toxicity and the anti
      inflammatory effect of plant recipes used in Rwanda against asthma in order to
      select potential candidates for further characterization of the active compounds.
      MATERIALS AND METHODS: Water (aqueous) and methanol-dichloromethane (organic)
      extracts from selected folkloric recipes were submitted for toxicity test on THP
      1 derived macrophages using CellTiter-Glo Luminescent Cell Viability Assay. The
      evaluation of the anti-inflammatory effect of the plant extracts was carried out
      using the Caspase-Glo 1 Inflammasome assay on THP-1 -derived macrophages.
      RESULTS: Most of both organic and aqueous extract showed more than 95% of cell
      viability up to 200 ug/ml, except for R03Cn organic extract that inhibited 25% of
      the cell viability. Plant extracts inhibited caspase-1 activation in THP-1
      derived macrophages in a dose-dependent manner. Four extracts (R03Cn and R07Kn
      aqueous extracts, R10MK and R19Sz organic extracts) strongly downregulated the
      activation of caspase-1 (more than 70% at 50 ug/ml). In general, organic extracts
      exhibited better caspase-1 inhibitory effects than their aqueous counterparts.
      CONCLUSIONS: The inhibition of inflammasome/caspase-1 is one of key mechanisms of
      action in asthma. Some traditional recipes are active on this mechanism and are
      thus strong candidates for the treatment of asthma and other inflammasome
      mediated diseases. Further investigations are needed to characterize active
      molecules.

PMID- 30118838
TI  - Hepatoprotective effects of green Capsicum annum against ethanol induced
      oxidative stress, inflammation and apoptosis in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Capsicum annum L. (CA) is used extensively as a
      spice and is a rich source of antioxidant vitamins. It has long been used in
      Indian, Native American, and Chinese traditional medicine as a carminative and an
      appetizer that normalizes liver function. However, its hepato-protective activity
      has so far not been studied. AIM OF THE STUDY: The present study was undertaken
      to evaluate the efficacy of aqueous extract of CA at two different doses (125
      mg/kg body weight and 250 mg/kg body weight), against ethanol induced oxidative
      stress and apoptosis in liver tissue. MATERIALS AND METHODS: Adult male Wistar
      rats, weighing 150-200 g, were randomly grouped (n = 6) and treated with ethanol
      (2 g/kg bw, i.p.), CA125 (125 mg/kg bw, i.p.), CA250 (250 mg/kg bw, i.p.),
      ethanol with CA (similar doses), and control (0.5 ml normal saline, i.p.) for 30
      days. Lipid peroxidation (LPO) and reduced glutathione content (GSH) in tissue
      homogenate, along with catalase (CAT), superoxide dismutase (Cu-Zn-SOD & Mn-SOD),
      glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-s
      transferase (GST) and glucose-6-phosphate dehydrogenase (G-6-P-D) activity were
      evaluated. Serum levels of alanine transaminase (ALT), aspartate transaminase
      (AST), alkaline phosphate (ALP), triglyceride (TG), total cholesterol (CHLS),
      high density lipoprotein (HDL), low density lipoprotein (LDL) very low density
      lipoprotein (VLDL), tumour necrotic factor alpha (TNF-alpha) and interleukin 6
      (IL-6) were also measured using ELISA kits. Histopathological evaluation of the
      hepatic tissue was performed by hematoxylin and eosin (H&E) and periodic acid
      schiff (PAS) staining. TUNEL assay was performed for apoptosis detection.
      RESULTS: Ethanol significantly (p < 0.001) increased ALT, AST, ALP, TNF-alpha, IL
      6, LPO, Cu-Zn-SOD, GST, GPx, TG, CHLS, LDL, VLDL levels, along with significant
      (p < 0.001) decrease in HDL, Mn-SOD, CAT, GSH, GR and G6PD activity. Co
      administration of CA along with ethanol alleviated changes in the above
      parameters (p < 0.001) in a dose-dependent manner and also reduced the number of
      apoptotic death cells. Histo-pathological and histo-chemical studies of liver
      sections also ascertained the outcomes of this study. CONCLUSION: Thus, it can be
      concluded that the aqueous extract of green CA can exert a protective effect
      against ethanol induced hepato-toxicity. The possible mechanism may be by acting
      as an antioxidant; preventing ethanol induced apoptosis and reducing pro
      inflammatory cytokine levels.

PMID- 30118839
TI  - Polo-like kinase 1 inhibitor BI 6727 induces DNA damage and exerts strong
      antitumor activity in small cell lung cancer.
AB  - The prognosis of small cell lung cancer (SCLC) is poor despite its good initial
      response to chemotherapy. Polo-like kinase 1 (PLK1) is a crucial mitotic
      regulator that is overexpressed in many tumors, and its overexpression is
      associated with tumor aggressiveness and a poor prognosis. However, its role in
      SCLC is still poorly characterized. Based on immunohistochemistry findings, the
      PLK1 protein is expressed at higher levels in SCLC tumor samples than in normal
      lung tissue samples. The selective PLK1 inhibitor BI 6727 significantly induced
      the inhibition of proliferation and apoptosis in a dose-dependent manner in SCLC
      cell lines. FACS analysis showed an increase in the population of cells in the
      G2/M phase, followed by DNA damage and the consequent activation of the ataxia
      telangiectasia and Rad3-related (ATR)/ataxia telangiectasia mutated (ATM)
      Chk1/Chk2 checkpoint pathway. In addition, BI 6727 treatment resulted in clearly
      attenuated growth and apoptosis in NCI-H446 xenografts. The level of histone H2AX
      phosphorylation at serine-139 (gammaH2AX) was markedly increased both in vitro
      and in vivo. Our findings indicate that BI 6727 has therapeutic potential for
      SCLC patients.

PMID- 30118840
TI  - USP9X inhibition improves gemcitabine sensitivity in pancreatic cancer by
      inhibiting autophagy.
AB  - Gemcitabine is the cornerstone of pancreatic cancer treatment. Although effective
      in most patients, development of tumor resistance to gemcitabine can critically
      limit its efficacy. The mechanisms responsible for this phenomenon remain
      elusive, but evidence suggests that ubiquitin-specific peptidases (USPs) may be
      key regulators in cancer chemo-resistance. The present study aimed to investigate
      the role of USP9X in gemcitabine resistance using in vitro pancreatic cell lines
      and a mouse xenograft model. We found that the expression of USP9X in pancreatic
      cancer cells was positively correlated with gemcitabine resistance, and that
      inhibition of USP9X by WP1130 sensitized pancreatic cancer cells to gemcitabine.
      Gemcitabine induced autophagy, and blocking autophagy with chloroquine improved
      sensitivity to gemcitabine. We also found that WP1130 inhibited gemcitabine
      induced autophagy, and blocking autophagy abolished the sensitization effect of
      WP1130 on gemcitabine in pancreatic cancer cells. Finally, combined gemcitabine
      and WP1130 treatment enhanced the anti-tumor effect of gemcitabine by suppressing
      autophagy in vivo. Taken together, these results demonstrate that inhibition of
      USP9X sensitized pancreatic cancer cells to gemcitabine by inhibiting autophagy,
      which provides a novel insight into gemcitabine resistance in pancreatic cancer.

PMID- 30118842
TI  - PTEN deficiency confers colorectal cancer cell resistance to dual inhibitors of
      FLT3 and aurora kinase A.
AB  - PTEN is a tumor suppressor found mutated in many cancers. From a synthetic
      lethality drug screen with PTEN-isogenic colorectal cancer cells, we found that
      mutant-PTEN cells were resistant to dual inhibitors of FLT3 and aurora kinase-A,
      including KW2449 and ENMD-2076. KW2449 significantly reduced the viability of
      wildtype-PTEN cells causing apoptosis, while little effect was observed in mutant
      PTEN counterparts. Transcriptome profiling showed that members of PI3K-AKT
      signaling pathway were strongly changed in cells after KW2449 treatment,
      indicating a potential role of the pathway in drug resistance. We found that
      KW2449 caused a dose-dependent, biphasic induction of AKT phosphorylation at
      Ser473 in mutant-PTEN cells. Co-treatment with the inhibitors of its upstream
      signaling completely abolished the reactivation of AKT phosphorylation by KW2449
      and reversed the drug resistant phenotype. These data suggest that reactivation
      of AKT phosphorylation at Ser473 is a key factor to confer drug resistant
      phenotype of mutant-PTEN cells to the dual inhibitors and that proper drug
      combinations that shut down AKT reactivation is necessary for the effective
      treatment of mutant-PTEN cancer with the dual inhibitors in clinical settings.

PMID- 30118843
TI  - Designer hydrogels: Shedding light on the physical chemistry of the pancreatic
      cancer microenvironment.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of
      cancer mortality in the United States, with a 5-year survival of ~8%. PDAC is
      characterized by a dense and hypo-vascularized stroma consisting of proliferating
      cancer cells, cancer-associated fibroblasts, macrophages and immune cells, as
      well as excess matrices including collagens, fibronectin, and hyaluronic acid. In
      addition, PDAC has increased interstitial pressures and a hypoxic/acidic tumor
      microenvironment (TME) that impedes drug delivery and blocks cancer-directed
      immune mechanisms. In spite of increasing options in targeted therapy, PDAC has
      mostly remained treatment recalcitrant. Owing to its critical roles on governing
      PDAC progression and treatment outcome, TME and its interplay with the cancer
      cells are increasingly studied. In particular, three-dimensional (3D) hydrogels
      derived from or inspired by components in the TME are progressively developed.
      When properly designed, these hydrogels (e.g., Matrigel, collagen gel, hyaluronic
      acid-based, and semi-synthetic hydrogels) can provide pathophysiologically
      relevant compositions, conditions, and contexts for supporting PDAC cell fate
      processes. This review summarizes recent efforts in using 3D hydrogels for
      fundamental studies on cell-matrix or cell-cell interactions in PDAC.

PMID- 30118841
TI  - New compound ChlA-F induces autophagy-dependent anti-cancer effect via
      upregulating Sestrin-2 in human bladder cancer.
AB  - ChlA-F is a novel conformation-derivative of Cheliensisin A, styryl-lactone
      isolates that show potent anti-tumor potential in vivo and vitro. However, the
      anti-cancer activity and its potential mechanisms underlying ChlA-F action have
      never been explored. In the present study, we evaluated the potency of ChlA-F on
      autophagy-mediated anchorage-independent growth inhibition in human high-grade
      invasive bladder cancer (BC) cells. We found that ChlA-F treatment significantly
      inhibited anchorage-independent growth of human BC cells by inducing autophagy in
      a Sestrin-2 (SESN2)-dependent fashion. Our results revealed that ChlA-F treatment
      specifically induced SESN2 expression via increasing its transcription and mRNA
      stability. On one hand, ChlA-F treatment markedly attenuated Dicer protein
      abundance, in turn abolishing miR-27a maturation and further relieving miR-27a
      binding directly to SESN2 mRNA 3'UTR, thereby promoting SESN2 mRNA stabilization.
      On the other hand, ChlA-F treatment promoted Sp1 abundance and consequently
      mediated SESN2 transcription. These results demonstrate that its activation of
      the autophagic pathway through specifically promoting SESN2 expression mediates
      the anti-cancer effect of ChlA-F, which offers insights into the novel anti
      cancer effect of ChlA-F on BC, as well as providing therapeutic alternatives
      against human BC.

PMID- 30118844
TI  - TGF-beta-induced STAT3 overexpression promotes human head and neck squamous cell
      carcinoma invasion and metastasis through malat1/miR-30a interactions.
AB  - Aberrant signal transducer and activator of transcription 3 (STAT3) signaling is
      a critical factor that drives the invasion and metastasis of head and neck
      squamous cell carcinoma (HNSCC). However, the underlying mechanisms of STAT3
      overexpression and regulation of HNSCC metastasis remain unknown. In the current
      study, we demonstrated that upregulated TGF-beta may promote epithelial
      mesenchymal transition (EMT) through STAT3 activation. In addition, we explored
      the contributions of STAT3 to HNSCC with a specific focus on its transcriptional
      regulation and its interaction with the long noncoding RNA (lncRNA) metastasis
      associated lung adenocarcinoma transcript 1 (malat1). Chromatin
      immunoprecipitation (ChIP) and luciferase reporter assays revealed that STAT3
      could bind to the malat1 promoter region and transcriptionally activate malat1
      expression; then, malat1 interacted reciprocally with miR-30a, inducing EMT and
      accelerating HNSCC metastasis. In summary, our discoveries illuminate how
      aberrant STAT3 activation confers an oncogenic function in HNSCC and therefore
      may provide a theoretical foundation for STAT3 as a therapeutic target in HNSCC.

PMID- 30118845
TI  - Tim-4 promotes the growth of colorectal cancer by activating angiogenesis and
      recruiting tumor-associated macrophages via the PI3K/AKT/mTOR signaling pathway.
AB  - T-cell immunoglobulin domain and mucin domain-4 (Tim-4) is overexpressed in
      several tumors and is correlated with enhanced tumor development and metastasis.
      In this study, we investigated the physiological alterations and molecular events
      related to Tim-4 overexpression in a mouse model of colorectal cancer (CRC). In
      the current study, we observed that Tim-4 is upregulated in CRC tissues compared
      with neighboring normal tissues. In addition, statistical analysis revealed that
      elevated Tim-4 expression was strongly linked to distant metastasis, TNM stage
      and reduced overall survival duration in CRC patients. An orthotopic model was
      employed to explore the function of Tim-4 in CRC development through the
      implantation of Tim-4-overexpressing CT26 murine colon adenocarcinoma cells. It
      was observed that Tim-4 overexpression considerably enhanced CRC tumorigenesis in
      vivo and promoted angiogenesis through the upregulation of vascular endothelial
      growth factor (VEGF). In CT26 cells, Tim-4 overexpression increased the aldehyde
      dehydrogenase-1 (ALDH1) level, indicating an increase in cancer stem cell (CSC)
      like properties. Furthermore, we determined that Tim-4 activates PI3K/AKT/mTOR
      signaling in CRC cells. Tim-4-overexpressing cancer cells recruited tumor
      associated macrophages (TAMs), thereby accelerating cancer development.
      Therefore, our results strongly indicate that Tim-4 overexpression promotes
      proliferation and tumor stroma remodeling in CRC. PI3K/AKT/mTOR activation might
      be crucial in Tim-4-linked tumor development. This finding might offer a new
      strategy for therapeutic intervention.

PMID- 30118846
TI  - Vaccine-induced antibody level as the parameter of the influence of environmental
      salinity on vaccine efficacy in Nile tilapia.
AB  - To effectively increase production and improve economic returns, the co-culture
      of Nile tilapia (Oreochromis niloticus) and marine shrimp has been adopted in
      many countries, including China. Although O. niloticus is an euryhaline fish that
      can tolerate elevated salinities and even full-strength seawater, fluctuations in
      salinity levels can undoubtedly induce stress and affect the immune response of
      this fish. Therefore, this study assessed the impact of salinity on vaccine
      efficacy in Nile tilapia, which used serum antibody level as a surrogate marker
      to detect vaccine efficacy. Nile tilapia were acclimatized to 0, 10, 20, or 30
      ppt salinity, and then immunized with a formalin-inactivated Streptococcus
      agalactiae vaccine. Significantly lower levels of antibody in vaccinated fish
      were found at 20 and 30 ppt salinity compared to 0 and 10 ppt salinity. White
      blood cell counts, absolute blood lymphocyte counts, and serum bactericidal
      activity levels were all significantly lower in vaccinated fish at 20 and 30 ppt
      salinity. Elevated cortisol levels were detected in all of the fish exposure to
      salinity. Concentrations of serum electrolytes (Na+ and Cl-) were significantly
      higher in fish at 30 ppt salinity, as compared to fish at lower salinities.
      Furthermore, the mRNA transcription levels of three of the immune-related genes
      analyzed (IgM, IL-1beta, and IFN-gamma, but not Hsp70) were significantly
      inhibited in the vaccinated fish at 20 and 30 ppt salinity. A suppressed immune
      response and decreased vaccine efficacy were also indicated by the lower survival
      rate of vaccinated fish at 20 ppt salinity when challenged with S. agalactiae.
      Therefore, salinities >=20 ppt negatively affected antibody production in Nile
      tilapia, ultimately affecting vaccine efficacy.

PMID- 30118848
TI  - Two novel camptothecin derivatives inhibit colorectal cancer proliferation via
      induction of cell cycle arrest and apoptosis in vitro and in vivo.
AB  - At present, chemotherapy is still to be the preferred and most significant
      therapeutic strategy for cancer patients in clinical practice. Although
      Camptothecin (CPT) has been discovered for over half century, a series of CPT
      derivatives such as Topotecan (TPT) and irinotecan (CPT-11) have been approved
      and are still to be the first-line medicines for clinical application. Up to now,
      the topoisomerase 1 inhibitor continues to be a significant drug development
      research field. Based on previous study of the structure-activity relationship,
      we consider that the introduction of lipophilic group at C7 position can prolong
      the retention time and the hydroxyl esterification at C20 can eliminate the
      hydrogen bond interaction, stabilize the E-lactone form and promote the anti
      cancer effect. In this study, we carried out an optimization at C7 and C20
      positions to afford two CPT derivatives 3g and 3j. Firstly, we predicted the
      possibly binding sites of two compounds with topoisomerase 1 by molecular
      docking. Then we evaluated the anti-proliferation effect of the two novel
      derivatives and compared the IC50 with CPT-11. Furthermore, the induction of cell
      cycle arrest and apoptosis was explored through karyomorphology, flow cytometry
      (FCM) and Western blot analysis. At last, we evaluated the anti-cancer effect and
      detected the mechanism in colorectal cancer xenograft model. In brief, all the
      data showed that the novel CPT derivatives (3g and 3j) could inhibit colorectal
      cancer proliferation via induction of cell cycle arrest and apoptosis in vitro
      and in vivo. It suggested that the two agents may be a new potential therapeutic
      strategy in the future.

PMID- 30118847
TI  - Biotinylated PAMAM G3 dendrimer conjugated with celecoxib and/or Fmoc-l-Leucine
      and its cytotoxicity for normal and cancer human cell lines.
AB  - Tumors still remain one of the main causes of mortality due to the lack of
      effective anti-cancer therapy. Recently it has been shown, that overexpression of
      inducible cyclooxygenase-2 (COX-2) and decrease of peroxisome proliferator
      activated receptor gamma (PPARgamma) expression accompany many malignances,
      therefore, it has been proposed, that COX-2 inhibitors and PPARgamma agonists are
      potential candidates for anticancer therapy and their synergistic, antineoplastic
      action has been described. In the present study a COX-2 inhibitor (celecoxib)
      and/or PPARgamma agonist (Fmoc-l-Leucine) were conjugated with the biotinylated
      G3 PAMAM dendrimer to form a three different constructs targeted to cells with
      increased biotin uptake. All conjugates were characterized by the NMR
      spectroscopy. Investigation of three types of human cells: normal skin
      fibroblasts (BJ), immortalized keratinocytes (HaCaT) and cancer lines:
      glioblastoma (U-118 MG) and squamous cell carcinoma (SCC-15) revealed similar
      biotin labeled ATTO590 accumulation (after 24 h), except for SCC-15 with
      significantly lower loading. Constitutive expression of COX-2 protein was
      confirmed in all tested cells with significantly higher levels (2-2.5 times) in
      both cancer lines. Comparison of cytotoxicity of the new synthetized dendrimers
      clearly documented the highest cytotoxicity of the G31B16C15L dendrimer
      conjugated with both drugs (1: 1) as compared with drugs alone and single
      conjugates. Additive effects of construct with both compounds were shown for
      fibroblasts and both cancer cell lines in the order BJ > U-118 MG > SCC-15 with
      IC50 in the range: 0.69, 1.44 and 2.22 MUM, respectively and lowest cytotoxicity
      in HaCaT cells (IC50 = 2.88). Our results showed, that biotinylated G3 PAMAM
      dendrimers substituted with COX-2 inhibitor, celecoxib, and PPARgamma agonist,
      Fmoc-l-Leucine (1:1) may be a good candidate for local therapy of glioblastoma
      but not a skin cancer. Since the effect of PPARgamma agonists on COX-2 expression
      vary depending upon the cell type, specificity of used agonist and the presence
      of other environmental factors, it is necessary to carefully evaluate the
      response of chosen drugs on the target cells.

PMID- 30118849
TI  - Origins, and formulation implications, of the pKa difference between boronic
      acids and their esters: A density functional theory study.
AB  - The purpose of this study is to try to identify the etiology and formulation
      implications of the significant pKa drop in aqueous solution that occurs when
      boronic acids are reversibly esterified by reaction with alcohols, especially 1,2
      diols. Experimental studies have shown that conversion of a boronic acid to a
      boronic acid ester, both Lewis acids, is accompanied by an increase in the
      acidity, that is, a lowering of the pKa value in aqueous solution. The drop in
      pKa value has significant implications for the formulation of boronic acid-based
      drugs. Specifically, in the presence of 1,2-diols, a DeltapKa, a drop, of about 3
      pKa units has been observed for several boronic acids, including boron-based
      drugs that have demonstrated value as active pharmaceutical ingredients. Boric
      acid itself shows an even larger drop of about 4 units. Here, electronic
      structure calculations are used to investigate the origins of this pKa change.
      Specifically, density functional theory (DFT) is used to predict the DeltapKa for
      a model boronic acid, methylboronic acid, to two of its esters, the dimethyl
      ester and the cyclic ester with ethylene glycol. The approach is validated by
      accurately predicting the experimentally observed increased acidity of the cyclic
      boronic acid ester relative to the corresponding boronic acid. The origins of the
      acidity difference are examined in detail. Analysis shows that the primary origin
      is an electronic effect with a smaller contribution due to the reduced structural
      flexibility of the boronic ester.

PMID- 30118850
TI  - P-glycoprotein expression in the gastrointestinal tract of male and female rats
      is influenced differently by food.
AB  - The aim of this study was to explore the influence of food on P-glycoprotein (P
      gp) relative expression in both male and female rats, and its effect on
      intestinal permeation of P-gp substrates (ranitidine and ganciclovir) and a P-gp
      non-substrate (metformin). The intestine of 12 male and 12 female Wistar rats
      were excised and segmented into the duodenum, jejunum, ileum and colon. P-gp
      extracted from each segment was then determined via Western-blotting. In male
      rats, the relative P-gp expression decreased significantly after food intake in
      all segments of the intestine except in the duodenum. The most notable change was
      demonstrated in the colon where relative expression decreased from 1.75 +/- 0.36
      in the fasted-state to 0.31 +/- 0.15 in the fed-state. In female rats, a
      fundamentally different result was observed. Food ingestion resulted in a
      significant increase in relative P-gp expression in all regions of the intestine
      except in the colon. The largest difference was observed in the jejunum of the
      fed-state female rat intestine where P-gp expression was 1.76 +/- 0.95 which was
      a six-fold increase from the fasted state at 0.34 +/- 0.13. Intestinal permeation
      studies in an Ussing chamber showed that both ganciclovir and ranitidine
      exhibited a sex difference in intestinal permeability in the fasted-state. No sex
      differences and food effects were observed on metformin small intestine
      permeability. The permeability results of the three drugs highly supported that
      there was a sex-related food effect on P-gp function in the small intestine. In
      summary, the current study reports stark differences between male and female rats
      at a physiological level relating to P-gp expression and the influence of food.

PMID- 30118851
TI  - Unilateral versus bilateral lower extremity motor deficit following complex adult
      spinal deformity surgery: is there a difference in recovery up to 2 year Follow
      Up?
AB  - BACKGROUND CONTEXT: Scoli-RISK-1 is a multicenter prospective cohort designed to
      study neurologic outcomes following complex adult spinal deformity (ASD). The
      effect of unilateral versus bilateral postoperative motor deficits on the
      likelihood of long-term recovery has not been previously studied in this
      population. PURPOSE: To evaluate whether bilateral postoperative neurologic
      deficits have a worse recovery than unilateral deficits. STUDY DESIGN: Secondary
      analysis of a prospective, multicenter, international cohort study. METHODS: In a
      cohort of 272 patients, neurologic decline was defined as deterioration of the
      American Spinal Injury Association Lower Extremity Motor Scores (LEMS) following
      surgery. Patients with lower extremity neurologic decline were grouped into
      unilateral and bilateral cohorts. Differences in demographics, surgical
      variables, and patient outcome measures between the two cohorts were analyzed.
      RESULTS: A total of 265 patients had LEMS completed at discharge. Unilateral
      decline was seen in 32 patients (12%), while 29 (11%) had bilateral symptoms. At
      2 years, there was no significant difference in either median LEMS (unilateral
      50.0, interquartile range [IQR] 47.5-50.0; bilateral 50.0, IQR 48.0-50.0, p=.939)
      or change in LEMS from baseline (unilateral 0.0, IQR -1.0 to 0.0; bilateral 0.0,
      IQR -1.0 to 0.0, p=.920). In both groups, approximately two-thirds of patients
      saw recovery to at least their preoperative baseline by 2 years postoperatively
      (unilateral n=15, 63%; bilateral n=14, 67%). The mean Scoliosis Research Society
      22R (SRS-22R) score at 2 years was 3.7+/-0.6 versus 3.2+/-0.6 (p=.009) for
      unilateral and bilateral groups, respectively. CONCLUSIONS: The prognosis for
      neurologic recovery of new motor deficits following complex adult spinal
      deformity is similar with both unilateral and bilateral weaknesses. Despite
      similar rates of neurologic recovery, patient reported outcomes for those with
      bilateral motor decline measured by SRS-22R are worse at 2 years after surgery.

PMID- 30118853
TI  - Surfactant protein B (SP-B) enhances the cellular siRNA delivery of proteolipid
      coated nanogels for inhalation therapy.
AB  - : Despite the many advantages of small interfering RNA (siRNA) inhalation therapy
      and a growing prevalence of respiratory pathologies, its clinical translation is
      severely hampered by inefficient intracellular delivery. To this end, we
      previously developed hybrid nanoparticles consisting of an siRNA-loaded nanosized
      hydrogel core (nanogel) coated with Curosurf(r), a clinically used pulmonary
      surfactant (PS). Interestingly, the PS shell was shown to markedly improve
      particle stability as well as intracellular siRNA delivery in vitro and in vivo.
      The major aim of this work was to identify the key molecular components of PS
      responsible for the enhanced siRNA delivery and evaluate how the complexity of
      the PS coat could be reduced. We identified surfactant protein B (SP-B) as a
      potent siRNA delivery enhancer when reconstituted in proteolipid coated hydrogel
      nanocomposites. Improved cytosolic siRNA delivery was achieved by inserting SP-B
      into a simplified phospholipid mixture prior to nanogel coating. This effect was
      observed both in vitro (lung epithelial cell line) and in vivo (murine acute lung
      injury model), albeit that distinct phospholipids were required to achieve these
      results. Importantly, the developed nanocomposites have a low in vivo toxicity
      and are efficiently taken up by resident alveolar macrophages, a main target cell
      type for treatment of inflammatory pulmonary pathologies. Our results demonstrate
      the potential of the endogenous protein SP-B as an intracellular siRNA delivery
      enhancer, paving the way for future design of nanoformulations for siRNA
      inhalation therapy. STATEMENT OF SIGNIFICANCE: Despite the therapeutic potential
      of small interfering RNA (siRNA) and a growing prevalence of lung diseases for
      which innovative therapies are needed, a safe and effective siRNA inhalation
      therapy remains non-existing due to a lack of suitable formulations. We
      identified surfactant protein B (SP-B) as a potent enhancer of siRNA delivery by
      proteolipid coated nanogel formulations in vitro in a lung epithelial cell line.
      The developed nanocomposites have a low in vivo toxicity and show a high uptake
      by alveolar macrophages, a main target cell type for treatment of inflammatory
      pulmonary pathologies. Importantly, in vivo SP-B is also critical for the
      developed formulation to obtain a significant silencing of TNFalpha in a murine
      LPS-induced acute lung injury model.

PMID- 30118852
TI  - Anogenital human papillomavirus virus DNA and sustained response to the
      quadrivalent HPV vaccine in women living with HIV-1.
AB  - OBJECTIVES: People living with HIV have increased Human Papillomavirus (HPV)
      related lesions and malignancies. We describe HPV DNA recovered from the cervix
      and anal canal, explore the effect of vaccination on HPV detection, and examine
      the durability of vaccine titers in women living with HIV-1 who were vaccinated
      with the quadrivalent HPV vaccine. METHODS: AIDS Clinical Trials Group A5240 was
      a prospective study of the quadrivalent HPV (qHPV) vaccine in 315 HIV-1 infected
      women in three CD4 strata (A: >350, B; 201-350, C: <=200 cells/mm3). Vaccine was
      administered at entry, week 8 and week 24. Cervical and anal HPV DNA specimens
      were collected at baseline, weeks 28 and 52; serum for antibody testing was
      obtained at baseline, weeks 28 and 72. RESULTS: Vaccine antibody titers decreased
      across all four HPV types at week 72 compared to week 28. Lower proportions of
      sustained seropositivity were observed in women with lower CD4 counts for all
      four vaccine types, with the lowest titers for HPV 18. Despite the decrease, the
      geometric mean titer levels were above the seroconversion cut-off levels for all
      types except HPV 18 in the lowest CD4 stratum. Of the 174 participants who had a
      negative baseline HPV 16 antibody and developed antibody response at week 28,
      95%, 88%, and 86% retained seropositivity at week 72 in strata A, B, and C
      respectively. Lower antibody retention was observed in women with CD4 < 200
      compared to CD4 > 350 (p = 0.016). Anal HPV detection was more prevalent compared
      to cervical detection at all visits. Among high risk types, type 52, 31, 16, 18
      and 51 were the most common in the cervical compartment, while types 16, 35, 18,
      and 51 were the most prevalent in the anal canal at baseline (listed in the order
      of prevalence). Later detection of HPV not present at baseline was uncommon in
      either compartment. Serial recovery of HPV over time was more commonly observed
      in the anal canal. CONCLUSION: The qHPV vaccine elicits durable titer response
      above the seroconversion cut-off levels in HIV-infected women. However, the titer
      levels were substantially lower by Week 72, most noticeably in type 18. HPV DNA
      was detected more frequently in the anal canal. Detection of non-vaccine high
      risk HPV suggests a role for the nonavalent vaccine.

PMID- 30118854
TI  - A convolutional route to abbreviation disambiguation in clinical text.
AB  - OBJECTIVE: Abbreviations sense disambiguation is a special case of word sense
      disambiguation. Machine learning methods based on neural networks showed
      promising results for word sense disambiguation (Festag and Spreckelsen, 2017)
      [1] and, here we assess their effectiveness for abbreviation sense
      disambiguation. METHODS: Convolutional Neural Network (CNN) models were trained,
      one for each abbreviation, to disambiguate abbreviation senses. A reverse
      substitution (of long forms with short forms) method from a previous study was
      used on clinical narratives from Cleveland Clinic, USA, to auto-generate training
      data. Accuracy of the CNN and traditional Support Vector Machine (SVM) models
      were studied using: (a) 5-fold cross validation on the auto-generated training
      data; (b) a manually created, set-aside gold standard; and (c) 10-fold cross
      validation on a publicly available dataset from a previous study. RESULTS: CNN
      improved accuracy by 1-4 percentage points on all the three datasets compared to
      SVM, and the improvement was the most for the set-aside dataset. The improvement
      was statistically significant at p < 0.05 on the auto-generated dataset. We found
      that for some common abbreviations, sense distributions mismatch between the test
      and auto generated training data, and mitigating the mismatch significantly
      improved the model accuracy. CONCLUSION: The neural network models work well in
      disambiguating abbreviations in clinical narratives, and they are robust across
      datasets. This avoids feature-engineering for each dataset. Coupled with an
      enhanced auto-training data generation, neural networks can simplify development
      of a practical abbreviation disambiguation system.

PMID- 30118855
TI  - Risk prediction using natural language processing of electronic mental health
      records in an inpatient forensic psychiatry setting.
AB  - OBJECTIVE: Instruments rating risk of harm to self and others are widely used in
      inpatient forensic psychiatry settings. A potential alternate or supplementary
      means of risk prediction is from the automated analysis of case notes in
      Electronic Health Records (EHRs) using Natural Language Processing (NLP). This
      exploratory study rated presence or absence and frequency of words in a forensic
      EHR dataset, comparing four reference dictionaries. Seven machine learning
      algorithms and different time periods of EHR analysis were used to probe which
      dictionary and which time period were most predictive of risk assessment scores
      on validated instruments. MATERIALS AND METHODS: The EHR dataset comprised de
      identified forensic inpatient notes from the Wilfred Lopes Centre in Tasmania.
      The data comprised unstructured free-text case note entries and serial ratings of
      three risk assessment scales: Historical Clinical Risk Management-20 (HCR-20),
      Short-Term Assessment of Risk and Treatability (START) and Dynamic Appraisal of
      Situational Aggression (DASA). Four NLP dictionary word lists were selected: 6865
      mental health symptom words from the Unified Medical Language System (UMLS), 455
      DSM-IV diagnoses from UMLS repository, 6790 English positive and negative
      sentiment words, and 1837 high frequency words from the Corpus of Contemporary
      American English (COCA). Seven machine learning methods Bagging, J48, Jrip,
      Logistic Model Trees (LMT), Logistic Regression, Linear Regression and Support
      Vector Machine (SVM) were used to identify the combination of dictionaries and
      algorithms that best predicted risk assessment scores. RESULTS: The most accurate
      prediction was attained on the DASA dataset using the sentiment dictionary and
      the LMT and SVM algorithms. CONCLUSIONS: NLP, used in conjunction with NLP
      dictionaries and machine learning, predicted risk ratings on the HCR-20, START,
      and DASA, based on EHR content. Further research is required to ascertain the
      utility of NLP approaches in predicting endpoints of actual self-harm, harm to
      others or victimisation.

PMID- 30118856
TI  - Laser Uses in Noncoronary Arterial Disease.
AB  - BACKGROUND: In the past decade, excimer laser angioplasty (ELA) has emerged in
      the field of peripheral artery disease (PAD). Laser indications now extend to off
      label uses, such as in situ fenestration of aortic endograft. The aim of this
      study was to review the different therapeutics applications of lasers in arterial
      disease treatment. METHODS: We reviewed the English-language literature using the
      Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We
      selected 106 relevant papers. We excluded unrelated papers (n = 67), letters and
      commentaries (n = 6), and review articles (n = 7), leaving 26 articles to form
      the basis of this review. RESULTS: A total of 18 articles were included in the
      analysis of ELA applications in PAD. Nine articles were related to
      atherosclerotic plaques. With a mean follow-up of 15 +/- 7 months, primary
      patency was 65% +/- 20%. The mean distal embolism rate during the procedure was
      5%. Eight more articles focused on in-stent restenosis. The mean technical
      success was 98%, and the rate of distal embolism during the procedure was 9%.
      With a mean follow-up of 10 +/- 4 months, primary patency was 68% +/- 18%. Eight
      articles described "off-label" excimer laser indications in endovascular therapy,
      including 5 papers regarding in situ fenestrations for complex aortic aneurysms.
      CONCLUSION: Laser atherectomy and laser-assisted techniques are an important part
      of a vascular surgeon and interventionalist's armamentarium.

PMID- 30118857
TI  - Risk Factors for Restenosis after Drug-coated Balloon Angioplasty for Complex
      Femoropopliteal Arterial Occlusive Disease.
AB  - BACKGROUND: Currently, there exist limited data on patient outcomes following the
      use of drug-coated balloons (DCBs) to treat complex femoropopliteal arterial
      occlusive lesions. The aim of the this study is to investigate the outcomes of
      patient treated with DCBs and to identify the predictors of restenosis. METHODS:
      We retrospectively investigated medical records from 120 patients (137 limbs)
      treated with DCBs for femoropopliteal lesions at a single center between 2013 and
      2016. Primary patency, target lesion revascularization (TLR), and risk factors of
      restenosis were analyzed. RESULTS: There were 80 de novo and 57 in-stent
      restenosis lesions. Mean lesion length was 22.2 +/- 11.6 cm. The clinical primary
      patency was 85.2% at 1 year and 65.3% after 2 years. The TLR-free survival rate
      was 93.0% at 1 year and 87.1% after 2 years. Critical limb ischemia (CLI; hazard
      ratio [HR] 5.80, 95% confidence interval [CI] 1.26-26.68, P = 0.024) and
      hypercholesterolemia (HR 4.66, 95% CI 1.30-16.76, P = 0.018) were identified as
      independent predictors of restenosis. In addition, nonuse of cilostazol and
      popliteal artery involvement showed trends toward an increased risk of
      restenosis. CONCLUSIONS: Treatment with DCBs showed excellent primary patency and
      TLR-free survival at 1 year after the procedure. However, the primary patency
      continuously deteriorated beyond 1 year, suggesting a late catch-up phenomenon.
      The risk of restenosis after treatment with DCBs was significantly associated
      with CLI and hypercholesterolemia.

PMID- 30118858
TI  - A novel familial truncating mutation in the filamin C gene associated with
      cardiac arrhythmias.
AB  - The authors report for the first time a novel mutation in the FLNC gene
      associated with cardiac arrhythmias in two half-siblings. The FLNC gene on
      chromosome 7q32 encodes filamin C, which stabilizes the actin network within the
      cardiomyocyte. The proband is an 8-year-old asymptomatic patient with frequent
      premature ventricular contractions noted on serial monitoring. Interestingly, the
      proband and his half-brother harbored a heterozygous 13 base pair deletion that
      resulted in a frameshift mutation and introduction of a premature stop codon.
      Notably, the proband also had a very tragic family history of sudden death in
      young individuals involving three generations and five family members. Because of
      their concerning family history and arrhythmias, both siblings underwent off
      label implantable cardiac device placement for primary prevention of sudden
      cardiac death. Whether or not the FLNC mutation is associated with sudden cardiac
      death requires additional investigation and is beyond the scope of this
      manuscript. While previous studies have identified several mutations in the FLNC
      gene associated with dilated and hypertrophic cardiomyopathies, the goal of this
      study was to report a novel mutation in the FLNC gene that is associated with
      cardiac arrhythmias. The current study indicates that this mutation may help
      identify patients at risk for cardiac arrhythmias who would benefit from further
      cardiac evaluation.

PMID- 30118859
TI  - Oxylipins in cerebrospinal fluid in clinically isolated syndrome and relapsing
      remitting multiple sclerosis.
AB  - Although oxylipins are involved in inflammation, data on these lipid mediators in
      multiple sclerosis are sparse. In this study, a panel of oxylipins were analysed
      swith liquid chromatography tandem mass spectrometry in cerebrospinal fluid (CSF)
      from 41 treatment naive patients with clinically isolated syndrome (CIS) or
      relapsing remitting MS (RRMS) and 22 healthy controls. CSF levels of 9
      hydroxyoctadecadienoic acid (9-HODE) and 13-hydroxyoctadecadienoic acid (13-HODE)
      were significantly higher in patients than in healthy controls (9-HODE median 380
      nM (interquartile range 330-450 nM) in patients and 290 nM (interquartile range
      250-340 nM) in controls, 13-HODE median 930 nM (interquartile range 810-1080 nM)
      in patients and 690 nM (interquartile range 570-760 nM) in controls, p < 0.001 in
      Mann-Whitney U tests). 9-HODE and 13-HODE performed well for separation of
      patients and healthy controls (AUC 0.85 and 0.88, respectively, in ROC curve
      analysis). However, baseline CSF levels of the oxylipins did not differ between
      patients with signs of disease activity during one, two and four years of follow
      up and patients without. In conclusion, this study indicates that 9-HODE and 13
      HODE levels are increased in CSF from CIS and RRMS patients compared with healthy
      controls, but does not support 9-HODE or 13-HODE as prognostic biomarkers of
      disease activity in patients during follow-up.

PMID- 30118860
TI  - Knowledge, attitude and practice (KAP) survey regarding antibiotic use among
      pilgrims attending the 2015 Hajj mass gathering.
AB  - BACKGROUND: Overuse and misuse of antibiotics have been reported in Hajj.
      However, little is known about Knowledge, Attitude and Practice (KAP) of pilgrims
      themselves in relation to these agents. METHODS: Adult pilgrims from seven
      countries attending the 2015 Hajj were interviewed using a structured KAP
      questionnaire. RESULTS: KAP information was collected from 1476 pilgrims.
      Misconceptions regarding antibiotics included that they: cure all diseases
      (24.6%); cure common cold and flu (63.0%); are used to stop fever (47.3%); have
      no side effects (43.2%). Negative attitudes included prophylactic use (50%), self
      medication (43.2%), non-compliance with therapy (63.5%) and storage of left-overs
      for future use (54.1%). In practice, 87.3% of pilgrims admitted to using non
      prescribed antibiotics, only 19.3% use antibiotic as directed by their doctor and
      54% do not usually check the expiry date of antibiotics before use. Over 60%
      brought antibiotics from their home country to KSA and 39.2% acquired non
      prescribed antibiotics in Saudi Arabia. KAP scores were higher among the younger
      age group (<=43 years old) and among those with healthcare-related work or
      education and increased with increasing levels of education. CONCLUSIONS:
      Multifaceted and multidisciplinary approaches, both in KSA and in pilgrims'
      countries of origin, are needed to address antibiotic misuse during Hajj.

PMID- 30118861
TI  - Expression, purification and molecular characterization of a novel transcription
      factor KcCBF3 from Kandelia candel.
AB  - Kandelia candel, a major species of mangrove in the tropical and subtropical
      area, is susceptible to low temperature in winter. K. candel was introduced into
      Zhejiang Province (the northern margin of South China) several decades ago, and
      suffered from low temperature causing growth retardation, in server cases, even
      death. To explore the molecular mechanisms of cold acclimation in K. candel, a
      novel C-repeat binding factor gene KcCBF3 (Genbank accession no. KF111715) of 729
      bp open reading frame (ORF) encoding a protein of 242 amino acid residues was
      isolated, expressed, purified and characterized. Multiple sequence alignment
      analysis revealed that KcCBF3 contained a highly conserved AP2/EREBP DNA-binding
      domain which consisting of 79 amino acid residues, as well as two CBF signature
      sequences. Phylogenetic analysis indicated that KcCBF3 belonged to the A-1
      subgroup of DREB subfamily based on the classification of AP2/EREBP transcription
      factors in Arabidopsis. Semi-quantitative RT-PCR showed that KcCBF3 transcripts
      were highly accumulated in roots and leaves, and could be induced by low
      temperature. Electrophoresis mobility shift assay (EMSA) demonstrated KcCBF3
      could bind to the core sequence (CCGAC) of cis-acting element C-repeat
      (CRT)/dehydration-responsive element (DRE) in vitro. These results implied that
      KcCBF3 might participate in the adaptation of K. candel to low-temperature stress
      by binding to CRT/DRE element.

PMID- 30118862
TI  - Chicory (Cichorium intybus) and wormwood (Artemisia absinthium) extracts exhibit
      strong larvicidal activity against mosquito vectors of malaria, dengue fever, and
      filariasis.
AB  - Vector-borne diseases transmitted by mosquitoes cause globally important diseases
      such as malaria, dengue fever, and filariasis. The incidence of these diseases
      can be reduced through mosquito control programs but these control programs
      currently rely on synthetic insecticides that can impact the environment, and has
      selected widespread mosquito resistance. Environment friendly and biodegradable
      natural insecticides discovered in plants offer an alternative approach to
      mosquito control. Here, we investigated extracts from root or aerial parts of
      Chicory (Cichorium intybus) and wormwood (Artemisia absinthium) against the early
      4th instar larvae of Anopheles stephensi (malaria vector), Aedes aegypti (dengue
      fever vector), and Culex quinquefasciatus (filariasis vector). The root and
      aerial parts extracts of A. absinthium and C. intybus at 200, 100, 50, 25 and
      12.5 ppm caused significant mortality of the tested mosquito species. Root
      extracts exhibited higher larvicidal activity that aerial part extracts. The
      highest larvicidal activity was recorded in methanol extract of roots of C.
      intybus with LC50 = 66.16, 18.88 and LC!90 = 197.56, 107.16 ppm for An.
      stephensi; LC50 = 78.51, 40.15 and LC90 = 277.31, 231.28 ppm for Ae. aegypti and
      LC50 = 103.99, 64.56 and LC!90 = 314.04, 247.54 ppm for Cx. quinquefasciatus.
      These results reveal potent mosquito larvicidal activity against vectors of
      malaria, dengue fever, and filariasis is present in extracts of chicory and
      wormwood.

PMID- 30118863
TI  - Minimally Invasive Spinal Surgery: How to Keep out of Trouble.
AB  - Innovative techniques have revolutionized minimally invasive surgeries, which has
      significant benefits for the patients. Despite the benefits, these advancements
      require a longer learning curve for an inexperienced surgeon. The authors have
      collected some pearls from their experience and from other surgeons. Tips and
      tricks about common MISS procedures such as minimally invasive endoscopic
      transforaminal lumbar disc and interlaminar discectomy, MIS, TLIF, LLIF, ALIF,
      spinal tumor excision, posterior cervical fixation and foraminotomy are
      described. How to stay out of trouble is explained with these surgeries. These
      techniques will help young surgeons to become proficient and achieve better
      outcome.

PMID- 30118865
TI  - Induction of plasmablasts by follicular helper T cell-CXCL13 axis upon occurrence
      of herpes zoster.
AB  - Herpes zoster (HZ) is a recurrent varicella zoster virus (VZV) infection.
      Follicular helper T (Tfh) cells produce IL-21 and CXCL13, which contributes to
      the differentiation of plasmablasts. Plasmablasts are involved in the VZV
      specific antibody production. We investigated the kinetics of circulating
      plasmablasts and circulating Tfh (cTfh) cells in 43 HZ patients. Plasma IL-21 and
      CXCL13 levels were also measured. We found an increase of circulating
      plasmablasts during the clinical course of HZ. The frequency of circulating
      plasmablasts positively correlated with VZV-specific IgG titers, frequency of
      activated cTfh cells, and plasma CXCL13 levels, but did not correlate with plasma
      IL-21 levels. In a representative case, the kinetics peaked in the order of cTfh
      cells, CXCL13, plasmablasts, and VZV IgG titer. These results suggest that cTfh
      CXCL13 may have a crucial role in the differentiation of B cells into VZV
      specific IgG-producing plasmablasts, resulting in boosting immunity against VZV
      reactivation.

PMID- 30118864
TI  - Extending Endovascular Embolization to Type A Spinal Perimedullary Arteriovenous
      Fistula Using Liquid Embolic Agent: Technical Nuances, Challenges and Initial
      Outcome.
AB  - BACKGROUND: The definitive treatment of perimedullary arteriovenous fistulas
      (PMAVFs) is warranted in view of the progressive neurologic decline noted with
      the conservative mode of management. The treatment options include microsurgical
      excision, endovascular embolization, or a multimodal approach. Because of the
      relatively larger size of the feeding arteries in type B and C PMAVFs, an
      endovascular approach is usually feasible. However, the endovascular treatment
      for type A lesions is technically challenging in view of near normal sized
      arterial feeders. Endovascular embolization using n-butyl cyanoacrylate is
      described; however, successful use of liquid embolic agents such as onyx or squid
      is not previously documented. CASE DESCRIPTION: The described 3 cases initially
      presented with insidious onset and gradually progressive paraparesis,
      paresthesia, and urinary symptoms. The imaging (magnetic resonance and digital
      subtraction angiography) revealed type A PMAVFs. The microcatheter could be
      successfully navigated close to the fistulous site, and complete obliteration of
      the fistula was achieved using ethylene vinyl alcohol copolymer (EVOH)-based
      liquid embolic agent, squid in all of our cases. The occlusion remained durable,
      and patients showed steady neurologic improvement in the follow-up period.
      CONCLUSIONS: Endovascular embolization of type A PMAVF using EVOH-based liquid
      embolic agent is feasible and could be considered as an effective alternative to
      surgery.

PMID- 30118866
TI  - Th1/17 cells, a subset of Th17 cells, are expanded in patients with active
      systemic lupus erythematosus.
AB  - Skewed cytokine production characterizes T cells in Systemic Lupus Erythematosus
      (SLE). Among Th17 cells that are expanded in lupus, a subset (Th1/17) retains the
      ability to produce IFNgamma. We aimed to analyze Th17 and Th1/17 cells in
      patients with SLE. Patients with active disease displayed increased percentages
      of circulating Tauh17 and Th1/17 cells. Stimulated T cells from patients with
      lupus secreted significantly more IL-17 compared to healthy donors. Also, T cells
      from patients with active SLE released significantly lower levels of IFN-gamma
      compared to controls. However, following stimulation, levels of IFN-gamma also
      rose significantly. Our data suggest that lupus Th1/17 cells are not only
      expanded but also functional. In summary, in this study it was shown that
      patients with active SLE display increased Th17 and functional Th1/17 cells. This
      impaired T-cell axis might represent a possible future therapeutic target.

PMID- 30118867
TI  - Neutrophils and neutrophil-lymphocyte ratio: Inflammatory markers associated with
      intimal-media thickness of atherosclerosis.
AB  - INTRODUCTION: Cardiac-cerebral vascular diseases (CCVDs) are global health
      problems due to the characteristic of high mortality. It is found that
      atherosclerosis (AS), a main cause of CCVDs, is significantly relevant to the
      change of intimal and media thickness. Neutrophil count (NEU) and neutrophil
      lymphocyte ratio (N/L) are recognized possible risk factors for atherosclerosis
      (AS). However, there are few studies on the separate relationship between carotid
      intimal thickness, media thickness and NEU, N/L. This study explored the
      respective effects of NEU and N/L on AS and intimal, media thickness. MATERIALS
      AND METHODS: The chi2, Spearman's rho test, and multiple linear regression were
      implemented to analyze the relevance between blood parameters and intimal-media
      thickness. The potential factors, affecting non-depression time (NDT), is
      identified by univariate Cox regression. ROC curve was performed to determine the
      ability of blood parameters to predict intimal-media thickness.
      Immunohistochemistry was implemented. RESULTS AND CONCLUSION: Based on chi2,
      Spearman's rho test and multiple linear regression, NEU is related with intimal
      thickness (P < 0.05). Furthermore, NEU can predict the intimal thickness through
      the ROC curve. What's more, N/L is a risk factor of carotid media thickness (P <
      0.05) by the Spearman's rho test, and is also correlated with poor NDT (P < 0.05)
      based on univariate Cox proportional regression analysis. Through ROC curve, N/L
      can predict the carotid media thickness. The carotid atherosclerotic endarterium
      is richest in macrophagocytes, and the arrangement of endotheliocytes is
      disordered. In summary, the increased NEU and N/L respectively have a strong
      correlation and precise predictability for carotid intimal and media thickness of
      atherosclerosis.

PMID- 30118868
TI  - The effect of unmeasurable endogenous plasma factor activity levels on factor
      VIII dosing in patients with severe hemophilia A.
AB  - BACKGROUND: Patients with hemophilia A are defined as "severe" if they present
      <0.01 IU mL-1 of clotting factor VIII (FVIII) activity endogenously (i.e. in
      absence of FVIII concentrate administration). However, an exact measurement of
      baseline FVIII is often impossible in such patients as the lower limit of
      quantification for most FVIII assays is around 0.01 IU mL-1, forcing assumptions
      to be made regarding endogenous circulating level. OBJECTIVE: This work aims to
      assess the consequences of different assumptions when selecting a prophylaxis
      regimen for the treatment of hemophilia A using a pharmacokinetics (PK)-driven
      approach. METHODS: Using a validated population PK model for conventional FVIII,
      we simulated the dose and frequency required to maintain various target troughs
      as a function of different postulated baseline levels. RESULTS: Patients with a
      true baseline of 0 IU mL-1 would require an additional 40 IU kg-1 to achieve any
      target trough below 0.05 IU mL-1, as compared to those with a true baseline close
      to 0.01 IU mL-1. When tailoring individual treatment regimens using a PK-based
      approach, baseline assumptions were highly influential and the assumption
      producing the most conservative dosing regimen was not consistent; rather, it
      depended on the particular scenario (e.g. increase vs. decrease of an observed
      trough). CONCLUSIONS: Targeting a trough close to the assay sensitivity creates a
      unique problem in forecasting the dose needed for optimal treatment of hemophilia
      that, while still without solution, deserves consideration when making dosing
      decisions.

PMID- 30118870
TI  - Reliable individual differences in fine-grained cortical functional architecture.
AB  - Fine-grained functional organization of cortex is not well-conserved across
      individuals. As a result, individual differences in cortical functional
      architecture are confounded by topographic idiosyncrasies-i.e., differences in
      functional-anatomical correspondence. In this study, we used hyperalignment to
      align information encoded in topographically variable patterns to study
      individual differences in fine-grained cortical functional architecture in a
      common representational space. We characterized the structure of individual
      differences using three common functional indices, and assessed the reliability
      of this structure across independent samples of data in a natural vision
      paradigm. Hyperalignment markedly improved the reliability of individual
      differences across all three indices by resolving topographic idiosyncrasies and
      accommodating information encoded in spatially fine-grained response patterns.
      Our results demonstrate that substantial individual differences in cortical
      functional architecture exist at fine spatial scales, but are inaccessible with
      anatomical normalization alone.

PMID- 30118869
TI  - 3D functional ultrasound imaging of pigeons.
AB  - Recent advances in ultrasound Doppler imaging have facilitated the technique of
      functional ultrasound (fUS) which enables visualization of brain-activity due to
      neurovascular coupling. As of yet, this technique has been applied to rodents as
      well as to human subjects during awake craniotomy surgery and human newborns.
      Here we demonstrate the first successful fUS studies on awake pigeons subjected
      to auditory and visual stimulation. To allow successful fUS on pigeons we
      improved the temporal resolution of fUS up to 20,000 frames per second with real
      time visualization and continuous recording. We show that this gain in temporal
      resolution significantly increases the sensitivity for detecting small
      fluctuations in cerebral blood flow and volume which may reflect increased local
      neural activity. Through this increased sensitivity we were able to capture the
      elaborate 3D neural activity pattern evoked by a complex stimulation pattern,
      such as a moving light source. By pushing the limits of fUS further, we have
      reaffirmed the enormous potential of this technique as a new standard in
      functional brain imaging with the capacity to unravel unknown, stimulus related
      hemodynamics with excellent spatiotemporal resolution with a wide field of view.

PMID- 30118871
TI  - Neural representations of the multidimensional self in the cortical midline
      structures.
AB  - Self-concept consists of self-identity that distinguishes self from other people
      and knowledge that describes one's own attributes in different dimensions.
      Because self-concept plays a fundamental role in individuals' social functioning
      and mental health, behavioral studies have examined cognitive processes of self
      identity and self-knowledge extensively. Nevertheless, how different dimensions
      of the self-concept are organized in multi-voxel neural patterns remains elusive.
      Here, we address this issue by employing representational similarity analyses of
      behavioral/theoretical models of multidimensional self-representation and blood
      oxygen level dependent responses, recorded using functional MRI, to judgments of
      personality traits, physical attributes and social roles of oneself, a close
      (one's mother) other, and a distant (celebrity) other. The multivoxel patterns of
      neural activities in the medial prefrontal cortex (mPFC) and posterior cingulate
      cortex (PCC) distinguished representations of the self from both close and
      distant others, suggesting a specific neural representation of the self-identity;
      and distinguished different dimensions of person knowledge of oneself, indicating
      dimension-sensitive neural representation of the self. Moreover, the pattern of
      PCC activity is more strongly coupled with dimensions of self-knowledge than self
      identity. Our findings suggest that multivoxel neural patterns of the cortical
      midline structures distinguish not only self from others but also discriminate
      different dimensions of the self.

PMID- 30118872
TI  - High diversity of Blastocystis subtypes isolated from asymptomatic adults living
      in Chiang Rai, Thailand.
AB  - Blastocystis is a common and broadly distributed microbial eukaryote inhabiting
      the gut of humans and other animals. The genetic diversity of Blastocystis is
      extremely high comprising no less than 17 subtypes in mammals and birds.
      Nonetheless, little is known about the prevalence and distribution of
      Blastocystis subtypes colonising humans in Thailand. Molecular surveys of
      Blastocystis remain extremely limited and usually focus on the central, urban
      part of the country. To address this knowledge gap, we collected stool samples
      from a population of Thai adults (n = 178) residing in Chiang Rai Province. The
      barcoding region of the small subunit ribosomal RNA was employed to screen for
      Blastocystis and identify the subtype. Forty-one stool samples (23%) were
      identified as Blastocystis positive. Six of the nine subtypes that colonise
      humans were detected with subtype (ST) three being the most common (68%),
      followed by ST1 (17%) and ST7 (7%). Comparison of subtype prevalence across
      Thailand using all publicly available sequences showed that subtype distribution
      differs among geographic regions in the country. ST1 was most commonly
      encountered in the central region of Thailand, while ST3 dominated in the more
      rural north and northeast regions. ST2 was absent in the northeast, while ST7 was
      not found in the center. Thus, this study shows that ST prevalence and
      distribution differs not only among countries, but also among geographic regions
      within a country. Potential explanations for these observations are discussed
      herewith.

PMID- 30118873
TI  - The evolutionary dynamics of H1N1/pdm2009 in India.
AB  - After the 2009 pandemic H1N1 outbreak, this new reassortant virus replaced the
      previous seasonal H1N1 and established itself in human populations. In 2014-2015,
      the H1N1/pdm2009 pandemic strain caused the worst influenza outbreak in India in
      recent years. It is still unclear whether this outbreak was due to a genetic
      change in the H1N1/pdm2009 virus. Here, we collected all available data from
      India, and used data from other South and Southeast Asian countries (Bangladesh,
      Myanmar, Nepal, Singapore, and Vietnam) that are geographically nearby India for
      comparison, to examine the evolutionary dynamics of this influenza virus. We
      detected signals of population expansion in both HA and NA in the 2014/2015
      season in India, which coincided with the outbreak in India of 2015. Signals of
      positive selection in HA in the 2012/2013 and 2013/2014 seasons, and in NA in the
      2012/2013 and 2014/2015 seasons were also found. These selective patterns were
      different from those seen in other South and Southeast Asian countries. However,
      none of the eight positively selected sites are endemic to India. The rapid
      circulation of H1N1/pdm2009 between these South and Southeast Asian countries may
      explain this result. Further studies are still needed to identify the genetic
      basis of the great 2015 outbreak in India.

PMID- 30118874
TI  - Why comprehensive datasets matter when inferring epidemic links or subgenotyping.

PMID- 30118875
TI  - Molecular evolution and functional divergence of IspD homologs in malarial
      parasites.
AB  - Malaria is one of the leading parasitic diseases to humans caused by Plasmodium
      falciparum. It is imperative to discover novel targets for the development of
      antimalarial drugs. The 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase
      (IspD) in 2-C-methyl-D-erythritol-4-phosphate pathway has been considered as a
      second in vivo off-target for antimalarial drugs discovery as its essentiality in
      malarial parasites and devoid in mammals. Our study was intended to reveal the
      molecular basis of its functional parts by inferring diversity, origin and
      evolution across important malarial parasites. Phylogenetic analyses revealed its
      conservation probability and sequence homology among bacterial IspD homologs. It
      also indicated that Plasmodium IspD homologs were distantly related to each other
      and their functional counterparts originated from different progenitor genes.
      Nucleotide-diphospho-sugar transferase fold and conserved domain of them might
      have evolved from green sulphur bacteria, whereas coiled-coil region and
      apicoplast targeting signal derived from protozoal origins. These homologs
      contained prospectively definable motifs subject to neutral or nearly neutral
      evolution on a scale that were diverged radically and subsequently converged in
      making spatial structural arrangements. Our genetic diversity analysis has shown
      a constructive signal for identifying the evolutionary constraints, which has
      imposed on their functional divergence in malarial parasites. Thus, this study
      provides a novel insight into our understanding of the molecular basis of the
      origin and evolution history of IspD homologs across apicomplexa.

PMID- 30118876
TI  - An evaluation of Bayesian age estimation using the auricular surface in modern
      Greek material.
AB  - Pelvic morphology is highly reflective of both sex and age changes in humans,
      making it a popular research focus in forensic anthropology. Relevant studies
      range from traditional descriptive to more complicated approaches involving
      statistical modeling, with the latter having become excessively popular in the
      last decades. The present study examines the performance of Bayesian statistics
      in age estimation based on the morphological changes observed on the iliac
      auricular surface. The aim is two-fold: a) to test whether a Bayesian approach
      can improve age-at-death estimation compared to the original Lovejoy et al.
      (1985a) and Buckberry and Chamberlain (2002) methods, and b) to explore the
      impact of adopting different samples as informative priors as well as for
      obtaining the transition analysis parameters. For this purpose, two modern Greek
      documented collections have been used, the Athens and the Cretan Collection. Our
      results found no clear improvement in age prediction when adopting Bayesian age
      estimation, with only one exception: Athenian males for the Buckberry and
      Chamberlain (2002) method. The choice of samples for transition analysis and as
      informative priors affected the results but this effect was statistically non
      significant.

PMID- 30118877
TI  - The frequency of dysphagia and its impact on adults with multiple sclerosis based
      on patient-reported questionnaires.
AB  - BACKGROUND: Multiple Sclerosis (MS) refers to a chronic inflammation of the
      central nervous system including the brain and spinal cord. Dysphagia is one of
      the symptoms that represent challenges in clinical practice for the management of
      MS patients. Dysphagia can result in serious complications leading to morbidity
      and death in late stages of MS. However, little attention is given to dysphagia,
      its symptoms and how it affects the quality of life of adults with MS.
      OBJECTIVES: The purpose of this study is to identify the frequency of dysphagia
      in adults with MS and determine the main symptoms suggestive of dysphagia and its
      impact on the patients' quality of life. METHOD: In total, 103 adults with MS
      agreed to participate in the study. Data were collected at the Multiple Sclerosis
      outpatient Clinic of a major metropolitan Australian hospital using patient
      reported questionnaires. RESULTS: 38% of adults with MS reported having
      swallowing problems that resulted in various physical and social consequences
      including but not limited to coughing, throat clearing, choking on food and
      liquid, reduced eating desire, increased eating duration and mealtime anxiety.
      CONCLUSION: Adults with MS-related dysphagia had reduced scores across all
      domains of swallowing-related quality of life. These findings support referral to
      speech-language pathologists for management of dysphagia from the early stages of
      the disease. Further work is required to determine whether early intervention for
      dysphagia can sustain or improve swallowing function as well as swallowing
      related quality of life domains further into the disease course.

PMID- 30118878
TI  - Adipose-derived stem cells: Effectiveness and advances in delivery in diabetic
      wound healing.
AB  - With the increasing global prevalence of diabetes mellitus, a significant rise in
      the number of patients suffering from non-healing wounds is expected. However,
      available treatments, such as revascularization surgery and foot care education
      are often insufficient to ensure satisfactory wound healing. One therapeutic
      strategy that has been identified as particularly promising utilizes adipose
      derived stem cells (ADSCs). Through a comprehensive literature search of
      published and ongoing studies, we aimed to provide an overview of the
      experimental basis, the scientific background, and advances in the delivery of
      ADSCs for treating non-healing diabetic wounds. ADSCs have the capacity to
      differentiate into multiple cell lineages and are considered an alternative to
      bone marrow-derived mesenchymal stem cells. They can be easily extracted from the
      adipose tissue and are capable of in-vitro expansion. The reviewed experimental
      studies showed that ADSCs can enhance diabetic wound healing through increasing
      epithelialization and granulation tissue formation, anti-inflammatory and anti
      apoptotic effects, and release of angiogenic cytokines. Moreover, few small
      clinical trials showed that ADSCs treatment in patients with diabetic ulcers
      caused enhanced ulcer evolution, lower pain scores, and improved claudication
      walking distances with no reported complications. In conclusion, ADSCs have a
      promising potential in the regenerative therapy of chronic diabetic wounds.
      However, larger studies should confirm their efficacy and long-term safety in
      diabetic patients.

PMID- 30118879
TI  - Premna integrifolia ameliorates cyclophosphamide-induced hepatotoxicity by
      modulation of oxidative stress and apoptosis.
AB  - The present study was designed to evaluate the ameliorative effect of ethyl
      acetate extract of Premna integrifolia L. (EAEPI) leaves in cyclophosphamide (CP)
      induced hepatic injury in mice. Mice were intoxicated with CP (200 mg/kg b. wt.,
      i.p.) for 5 weeks or EAEPI (400 and 600 mg/kg b. wt., orally) in combination with
      CP. The results demonstrated that EAEPI exerts protective effect against CP
      induced hepatotoxicity, as evident from restoration of altered haematological
      parameters and alleviations of liver marker enzymes in serum. EAEPI also
      attenuated oxidative stress and antioxidant markers as evident from reversal of
      lipid peroxidation, glutathione levels as well as activities of catalase and
      superoxide dismutase enzymes. Moreover, EAEPI attenuated apoptosis and
      histopathological liver tissue damage in CP-intoxicated mice. In conclusion,
      EAEPI could protect mice liver against cyclophosphamide toxicity by inhibiting
      oxidative stress and apoptosis.The protective activity of EAEPI may be due to
      presence of polyphenolic compounds as identified by UHPLC-Q-TOF-MS/MS.

PMID- 30118880
TI  - Effects of miR-26a-5p on neuropathic pain development by targeting MAPK6 in in
      CCI rat models.
AB  - MicroRNA are emerging as significant regulators of neuropathic pain progression.
      In addition, neuroinflammation contributes a lot to neuropathic pain. miR-26a-5p
      has been identified as an inflammation-associated miRNA in multiple pathological
      processes. However, little is known about the biological role of miR-26a-5p in
      neuroinflammation and neuropathic pain development. Therefore, we aimed to
      investigate the function of miR-26a-5p in neuropathic pain by establishing a rat
      model using chronic sciatic nerve injury (CCI). A significant decrease of miR-26a
      5p expression was observed in the spinal cord tissues form the CCI rats compared
      to the control group. Moreover, overexpression of miR-26a-5p significantly
      repressed neuropathic pain and neuroinflammation in CCI rats. MAPK6 was
      identified as a direct downstream target gene of miR-26a-5p and confirmed by dual
      luciferase reporter assays. As displayed, overexpression of miR-26a-5p greatly
      reduced MAPK6 levels in vitro and in vivo. Meanwhile, MAPK6 expression and miR
      26a-5p were oppositely correlated in CCI rats. Furthermore, up-regulation of
      MAPK6 obviously reversed the suppressive effect of miR-26a-5p on
      neuroinflammation and neuropathic pain progression. Taken these together, our
      results implied that miR-26a-5p could act as a negative regulator of neuropathic
      pain development through targeting MAPK6, which indicated that miR-26a-5p might
      serve as a potential therapeutic target for neuropathic pain.

PMID- 30118881
TI  - Calliandra surinamensis lectin (CasuL) does not impair the functionality of mice
      splenocytes, promoting cell signaling and cytokine production.
AB  - CasuL is a lectin (carbohydrate-binding protein) isolated from the leaf pinnulae
      of Calliandra surinamensis that is toxic against cancer cells. In this study, the
      effects of CasuL on the activation of immune cells were evaluated in BALB/c mice
      splenocytes. Assays measuring the changes in cytosolic calcium concentration
      ([Ca2+]cyt), mitochondrial membrane potential (DeltaPsim), and reactive oxygen
      species (ROS) levels associated with cell viability, proliferation, and cytokine
      and nitric oxide production were performed. The lectin (3.12-100 MUg/mL) did not
      induce apoptosis or necrosis of splenocytes, and treatment for 48 h at 12.5
      MUg/mL stimulated cell proliferation. High cytosolic ROS levels were found in
      cells incubated with CasuL (12.5 MUg/mL), but it did not affect [Ca2+]cyt,
      mitochondrial ROS, and DeltaPsim levels. Furthermore, CasuL promoted high IL-2
      and TNF-alpha production but did not affect nitric oxide release. In conclusion,
      CasuL was able to promote oxidative stress in mouse immune cells without inducing
      cell damage, and stimulated proliferation and cytokine production. These findings
      suggest the potential use of CasuL in future antitumoral and immunological
      targets.

PMID- 30118882
TI  - Sesamin and sesamolin reduce amyloid-beta toxicity in a transgenic Caenorhabditis
      elegans.
AB  - Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized
      by beta-amyloid (Abeta) plaques in the brain. At the present, there is no
      approved drug with a proven disease-modifying effect. Sesame seed (Sesame
      indicum) has long been known as a healthy food in Southeast Asian countries.
      Sesame lignans obtained from sesame seed possess antioxidant property that
      exhibit a variety of beneficial effects in various models. The objective of this
      study was to investigate the protective effects of sesame lignans including
      sesamin, sesamolin, and sesamol against Abeta toxicity in Caenorhabditis elegans
      (C. elegans) model of Abeta toxicity and to address whether these sesame lignans
      have a positive effect on lifespan extension. A transgenic C. elegans expressing
      human Abeta was used to investigate protective effects of sesame lignans against
      Abeta toxicity. Sesamin and sesamolin significantly alleviated Abeta-induced
      paralysis. The real-time PCR revealed that both sesamin and sesamolin did not
      affect the expression of Abeta transgene. However, we found that only sesamin
      inhibited Abeta oligomerization. These findings demonstrated that, among three
      sesame lignans tested, sesamin protected against Abeta toxicity by reducing toxic
      Abeta oligomers. Sesamin and sesamolin also significantly improved Abeta-induced
      defect in chemotaxis behavior and reversed the defect to normal. Moreover,
      sesamin prolonged median and mean lifespan of the wild type worm. On the other
      hand, sesamolin and sesamol failed to extend lifespan. These results offer
      valuable evidence for the future use of sesamin in the development of agents for
      the treatment of AD. It is also worth investigating the structure-activity
      relationship of lignan-related structures and their anti-Abeta toxicity
      activities in the future.

PMID- 30118883
TI  - Targeting NLRP3 inflammasome via acetylsalicylic acid: Role in suppressing
      hepatic dysfunction and insulin resistance induced by atorvastatin in naive
      versus alcoholic liver in rats.
AB  - BACKGROUND: NLRP3 inflammasome is described in many pathological conditions and
      is also involved in drug induced liver injury. AIM OF THE WORK: To investigate
      the role of NLRP3 inflammasome in liver injury induced by chronic alcohol and/or
      atorvastatin ingestion. MATERIALS AND METHODS: Sixty male Wistar rats were used.
      They were divided into 5 groups: (I) control naive (II) Alcoholic: given ethanol
      8 g/kg/day, p.o (III) Atorvastatin: given atorvastatin 10 mg/kg/day, p.o. (IV)
      Alcoholic + atorvastatin (V) Acetylsalicylic acid (ASA): given ASA 10 mg/kg/day,
      p.o together with alcohol and atorvastatin. Isolated perfused liver, biochemical
      and histological studies were done. RESULTS: Atorvastatin and alcohol induced
      liver inflammation with increasing the expression of NLRP3, IL-1beta and caspase
      8 immune-reaction. Atorvastatin and alcohol decreased the reduced form of
      glutathione in hepatic tissues and induced insulin resistance. ASA administration
      alleviated the hepatotoxic effects of alcohol and atorvastatin to a significant
      extent. CONCLUSIONS: Acetylsalicylic acid alleviated the hepatotoxic effects of
      alcohol and atorvastatin through decreasing the production of NLRP3 inflammasome
      in rats' liver.

PMID- 30118884
TI  - Electrocardiographic J wave: Early repolarization, Brugada wave, and conduction
      delay.

PMID- 30118885
TI  - Identification of paroxysmal atrial fibrillation subtypes in over 13,000
      individuals.
AB  - BACKGROUND: Paroxysmal atrial fibrillation (PAF) is broadly defined despite high
      variability in the occurrence and duration of PAF episodes. OBJECTIVE: The
      purpose of this study was to identify rhythm patterns in a large cohort of
      individuals with PAF who wore an ambulatory single-lead electrocardiogram (ECG)
      patch sensor as part of standard clinical care. METHODS: We performed a
      retrospective analysis of longitudinal rhythm data obtained from 13,293
      individuals with PAF. RESULTS: In this study, 7934 men and 5359 women with PAF
      wore an ambulatory single-lead ECG patch sensor for 11.4 days on average,
      experiencing 1,041,504 PAF episodes. The median daily rate of PAF was 1.21
      episodes per day (interquartile range [IQR] 0.31-4.99), and the median maximum
      duration per individual was 7.5 hours (IQR 2.4-18.6 hours). There was an inverse
      relationship between the duration of PAF episodes and the frequency in which they
      occurred, which became pronounced at moderate and high overall burdens of AF.
      This produced a spectrum of PAF flanked by 2 distinct subtypes of the disease:
      the staccato subtype, characterized by many, short AF episodes; and the legato
      subtype, characterized by fewer, longer episodes. Longer but less frequent
      episodes became more common with increasing age. Only 49.4% of individuals
      experienced an episode in the first 24 hours of monitoring, increasing to 89.7%
      after 1 week of monitoring. CONCLUSION: We identified subtypes of the disease
      that we labeled staccato and legato. Although further study is required, these
      subtypes may result from differing elements of pathophysiology and disease
      progression, and may confer differing stroke risks.

PMID- 30118886
TI  - What have we learned in the last 20 years? A comparison of a modern era pediatric
      and congenital catheter ablation registry to previous pediatric ablation
      registries.
AB  - BACKGROUND: Since the onset of pediatric catheter ablation, the pediatric
      electrophysiology community has reported outcomes via various registries (PAPCA
      [Prospective Assessment After Pediatric Cardiac Ablation], PCAR [Pediatric
      Catheter Ablation Registry]). Most recently, a modern era pediatric and
      congenital ablation registry (MAP-IT [Multicenter Pediatric and Congenital EP
      Quality Initiative]) was developed for eventual incorporation into the National
      Cardiovascular Data Registry (NCDR) IMPACT (Improving Pediatric and Adult
      Congenital Treatment) registry. OBJECTIVE: The purpose of this study was to
      describe initial findings from the MAP-IT pilot registry and to compare these
      findings to earlier registries. METHODS: Before entering the NCDR IMPACT
      registry, MAP-IT was active at 12 centers (11 in the United States) between
      October 2014 and April 2016. All electrophysiological studies for patients
      younger than 21 years and for patients of all ages with structural congenital
      heart disease were included. We compared the acute success, fluoroscopy and
      procedural times, and frequency of complications between MAP-IT and the earlier
      registries. RESULTS: Acute success rates have improved from the initial PCAR
      registry for both accessory and slow pathway substrates. Both fluoroscopy and
      procedural times have significantly decreased across the time periods
      (fluoroscopy time 47.6 +/- 40 minutes to 7.0 +/- 9.2 minutes; P <.001; procedural
      time 257 +/- 157 minutes to 166 +/- 84 minutes; P <.001). CONCLUSION: Acute
      success rates and fluoroscopy and procedural times in pediatric ablation all have
      improved over the last 25 years.

PMID- 30118887
TI  - Does a novel training in mental imagery reduce pathological worry?
AB  - Worry is a verbal and abstract thought activity with only little mental imagery
      involved. It has been shown that this processing bias leads to hampered emotional
      processing of worry topics so that worry is maintained in the long run. However,
      there is some evidence that mental imagery during worrying has the opposite
      effect: It leads to stronger emotional reactions than verbal thoughts and thereby
      fosters emotional processing of worry topics. In the present study, we examined
      whether training mental imagery reduces pathological worry. We compared the
      effect of a novel training in mental imagery (TMI; n = 37) on various worry
      related outcomes to a control training in verbal thinking (TVT; n = 38) and a
      waiting-list control group (n = 36) in a sample of pathologically high worriers.
      Both trainings showed significant within-group decline regarding e.g.
      pathological worry activity, worry-related impairment and anxiety assessed both
      one and five weeks after the training. Cohen's d on different outcome measures
      ranged from .39 to 1.17. However, unexpectedly, there were no significant
      differences between groups on any worry- or affect-related outcome measures. In,
      sum our training in general mental imagery skills turned out to be a promising
      intervention for the reduction of pathological worry. However, we found a
      training in verbal thinking to also have unexpected beneficial effects. The
      theoretical and clinical implications of these findings and methodological
      limitations of our study are discussed.

PMID- 30118888
TI  - Progesterone and cAMP synergize to inhibit responsiveness of myometrial cells to
      pro-inflammatory/pro-labor stimuli.
AB  - Progesterone (P4) acting through the P4 receptor (PR) isoforms, PR-A and PR-B,
      promotes uterine quiescence for most of pregnancy, in part, by inhibiting the
      response of myometrial cells to pro-labor inflammatory stimuli. This anti
      inflammatory effect is inhibited by phosphorylation of PR-A at serine-344 and 
      345 (pSer344/345-PRA). Activation of the cyclic adenosine monophosphate (cAMP)
      signaling pathway also promotes uterine quiescence and myometrial relaxation.
      This study examined the cross-talk between P4/PR and cAMP signaling to exert anti
      inflammatory actions and control pSer344/345-PRA generation in myometrial cells.
      In the hTERT-HMA/B immortalized human myometrial cell line P4 inhibited
      responsiveness to interleukin (IL)-1beta and forskolin (increases cAMP) and 8-Br
      cAMP increased this effect in a concentration-dependent and synergistic manner
      that was mediated by activation of protein kinase A (PKA). Forskolin also
      inhibited the generation of pSer344/345-PRA and expression of key contraction
      associated genes. Generation of pSer344/345-PRA was catalyzed by stress-activated
      protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Forskolin inhibited
      pSer344/345-PRA generation, in part, by increasing the expression of dual
      specificity protein phosphatase 1 (DUSP1), a phosphatase that inactivates mitogen
      activated protein kinases (MAPKs) including SAPK/JNK. P4/PR and forskolin
      increased DUSP1 expression. The data suggest that P4/PR promotes uterine
      quiescence via cross-talk and synergy with cAMP/PKA signaling in myometrial cells
      that involves DUSP1-mediated inhibition of SAPK/JNK activation.

PMID- 30118889
TI  - Preliminary screening and functional analysis of circular RNAs associated with
      hepatic stellate cell activation.
AB  - OBJECTIVE: To screen for circular RNAs (circRNAs) that are associated with the
      activation of hepatic stellate cell (HSC) by monitoring changes in liver circRNA
      expression in a model of liver fibrosis. METHODS: The classic mouse model of CCl4
      induced liver fibrosis was established and validated by histopathological
      examination. JS1 cells were activated by TGF-beta1 to model HSC activation in
      vitro. Differentially expressed circRNAs in the fibrotic liver tissues and JS1
      cells were determined using circRNA microarray, and some of those circRNAs were
      verified by RT-qPCR. The target genes of the above circRNAs were then predicted
      by bioinformatics analysis and summarized into a "circRNA-miRNA-mRNA" network
      diagram. Constructed plasmid mmu_circ_34116 siRNA was transfected to JS1 cells by
      Lipo2000, then we detected the expression changes of alpha-SMA. RESULTS: A total
      of 10,389 circRNAs were identified by microarray screening, and 69 differentially
      expressed circRNAs were detected in the fibrotic liver tissues with >2-fold
      difference in expression level relative to normal liver tissues (P < 0.05); 14
      circRNAs were up-regulated and 55 were down-regulated. Five differentially
      expressed circRNAs in fibrotic liver and JS1 cells were verified by RT-qPCR,
      while all five showed similar trends with the microarray results in the liver,
      only 3 circRNAs in the JS1 activation model were consistent with the microarray
      results while one showed no significant change and one circRNA was not detected.
      Bioinformatics analysis predicted that the "mmu_circ_34116/miR-22-3P/BMP7" signal
      axis might be involved in the activation of HSC. Transfection experiment
      confirmed that the expression of alpha-SMA is significantly elevated as a result
      of inhibitory expression of mmu_circ_34116. CONCLUSION: The circRNAs expression
      profile of liver tissue had changed in fibrosis mouse model, and some of these
      circRNAs may be associated with HSC activation. For instance, mmu_circ_34116
      would inhibit HSC activation.

PMID- 30118890
TI  - Enhanced expression of lncRNA TP73-AS1 predicts unfavorable prognosis for gastric
      cancer and promotes cell migration and invasion by induction of EMT.
AB  - Gastric cancer (GC) is a deadly disease with high incidence worldwide in recent
      years. Long noncoding RNAs (lncRNAs) were found to play imperative roles in many
      biological processes, such as cancer development and progression. Specifically,
      TP73-AS1, a novel cancer-related lncRNA, was documented to be up-regulated in
      several malignancies, but the clinical significance and functional role of TP73
      AS1 in GC is still unknown. RT-qPCR was performed to evaluate TP73-AS1
      transcription in GC tissue specimens and cell lines. In addition, the correlation
      between TP73-AS1 transcription and clinicopathologic features was further
      evaluated. Moreover, the effects of TP73-AS1 on GC cell were measured in vitro
      and in vivo. The data documented that TP73-AS1 was enhanced in GC tissues and
      cells, and TP73-AS1 transcription level was tightly associated with tumor size,
      TNM stage, and overall survival in 76 GC patients. What's more, decreased TP73
      AS1 could restrain cell growth and colony-forming capacity and promoted apoptosis
      partly by regulating Bcl-2/caspase-3 pathway. Importantly, TP73-AS1 could promote
      xenograft growth in vivo. Silencing of TP73-AS1 inhibited GC cell migratory and
      invasive properties partly by reversing snail-mediated epithelial-to-mesenchymal
      transition (EMT). Collectively, this study may help to develop the treatment
      strategy for GC.

PMID- 30118891
TI  - Bridging the gap by discerning SNPs in linkage disequilibrium and their role in
      breast cancer.
AB  - Breast Cancer is the most common cancer among women with several genes involved
      in disease susceptibility. As majority of genome-wide significant variants fall
      outside the coding region, it is likely that some of them alter specific gene
      functions. GWAS database was used to interpret the regulatory functions of these
      genetic variants. A total of 320 SNPs for breast cancer were selected via GWAS,
      which were entered into the SNAP web portal tool, to determine the one's found to
      be in Linkage Disequilibrium (r2 < 0.80). The resulting 2024 proxy SNP's were
      processed in RegulomeDB to predict their regulatory role. Of these, 1440 produced
      a score ranging from 1-6, whereas the remaining produced no data. Only the
      variants under score 4 (cut-off value) in RegulomeDB has been studied further.
      From these variants, 221 had scores of less than 4, indicating a high degree of
      potential regulatory role associated with them. Further study revealed that 61 of
      the 221 SNPs were reported to be genome-wide significant for breast cancer, 52 to
      be associated with other diseases, 99 as unconfirmed for association with breast
      cancer, leaving only 9 to be novel proxy SNPs linked to breast cancer. Therefore,
      the study further confirmed postulation of non-coding variants being linked to
      disease risk thereby, requiring additional validation through genome-wide
      association studies to substantiate their underlying mechanism.

PMID- 30118892
TI  - Fusobacterium nucleatum prosthetic hip infection: Case report and review of the
      literature of unusual anaerobic prosthetic joint infection.
AB  - The anaerobic Gram-negative rod Fusobacterium nucleatum is an oral commensal and
      periodontal pathogen that has been associated with a wide variety of infections,
      yet it is extremely rare to be associated with prosthetic joint infection. After
      an exhaustive literature review, only two cases of prosthetic joint infection by
      F. nucleatum have been previously reported. To our knowledge, the case we report
      on here is the first combined with periprosthetic abscess and related with
      hemochromatosis. We therefore sought to provide a comprehensive literature review
      of case reports or series of less commonly encountered anaerobic microorganisms
      isolated from prosthetic joint infections.

PMID- 30118893
TI  - Type C/D botulism in the waterfowl in an urban park in Italy.
AB  - This report describes an outbreak of botulism occurred among a free-living
      population of mallards (Anas platyrhynchos) and geese (Anser anser) in an urban
      park. Mortality rate among investigated population was 86,8% (118 dead out of
      136). Twenty-seven carcasses were collected for macroscopic examination and
      screened for microbiological, virological, toxicological investigations. A sick
      mallard was captured and neurological symptoms were observed. No causative agent
      of viral avian diseases was found in the examined animals and screening for
      environmental neurotoxic substances proved negative as well. In contrast,
      microbiological cultures from specimens tested positive for botulinum toxin
      producing clostridia. Blood serum and fecal extract of the sick mallard proved
      positive for botulinum neurotoxin in the standard mouse protection test using
      reference Clostridium botulinum type C antitoxin. Gene content of cultured
      strains showed a mosaic composition of bont/C and bont/D sequences, defining them
      as type C/D chimeric organisms.

PMID- 30118894
TI  - Development of an optimized broth enrichment culture medium for the isolation of
      Clostridium difficile.
AB  - Clostridium difficile is a spore forming bacterium and the leading cause of
      colitis and antibiotic associated diarrhoea in the developed world. Effective
      recovery of spores, particularly in low numbers, is imperative to obtain accurate
      prevalence data, due to the low number of spores found within non-clinical
      samples (<20/ml). Through comparison of C. difficile enrichment media, this study
      showed the importance of selecting an effective enrichment media. Commonly used
      broths, such as Cooked Meat broth, promote significantly less growth than other
      available broths such as Brain Heart Infusion broth, BHI. The optimization of BHI
      using selective antibiotics, moxalactam and norfloxacin, and sodium taurocholate
      at a concentration of 0.4%, allowed for high growth rate (0.465 h-1), short lag
      times (<14 h) and recovery of spores at low concentrations. The optimized broth,
      designated BHIMN-T, out-performed other commonly used broths so can be
      recommended for future studies.

PMID- 30118895
TI  - New Paradigm of Live Surgical Education: Synchronized Deferred Live Surgery.

PMID- 30118896
TI  - Opioid-Prescribing Guidelines for Common Surgical Procedures: An Expert Panel
      Consensus.
AB  - BACKGROUND: One in 16 surgical patients prescribed opioids becomes a long-term
      user. Overprescribing opioids after surgery is common, and the lack of
      multidisciplinary procedure-specific guidelines contributes to the wide variation
      in opioid prescribing practices. We hypothesized that a single-institution,
      multidisciplinary expert panel can establish consensus on ideal opioid
      prescribing for select common surgical procedures. STUDY DESIGN: We used a 3-step
      modified Delphi method involving a multidisciplinary expert panel of 6 relevant
      stakeholder groups (surgeons, pain specialists, outpatient surgical nurse
      practitioners, surgical residents, patients, and pharmacists) to develop
      consensus ranges for outpatient opioid prescribing at the time of discharge after
      20 common procedures in 8 surgical specialties. Prescribing guidelines were
      developed for opioid-naive adult patients without chronic pain undergoing
      uncomplicated procedures. The number of opioid tablets was defined using
      oxycodone 5 mg oral equivalents. RESULTS: For all 20 surgical procedures
      reviewed, the minimum number of opioid tablets recommended by the panel was 0.
      Ibuprofen was recommended for all patients unless medically contraindicated. The
      maximum number of opioid tablets varied by procedure (median 12.5 tablets), with
      panel recommendations of 0 opioid tablets for 3 of 20 (15%) procedures, 1 to 15
      opioid tablets for 11 of 20 (55%) procedures, and 16 to 20 tablets for 6 of 20
      (30%) procedures. Overall, patients who had the procedures voted for lower opioid
      amounts than surgeons who performed them. CONCLUSIONS: Procedure-specific
      prescribing recommendations may help provide guidance to clinicians who are
      currently overprescribing opioids after surgery. Multidisciplinary, patient
      centered consensus guidelines for more procedures are feasible and may serve as a
      tool in combating the opioid crisis.

PMID- 30118897
TI  - Final results of a randomized multicenter phase II study of alvocidib,
      cytarabine, and mitoxantrone versus cytarabine and daunorubicin (7 + 3) in newly
      diagnosed high-risk acute myeloid leukemia (AML).

PMID- 30118898
TI  - Imatinib resistance due to a novel and rare class of mutation at position S348
      (1043nt C->A) of Bcr/Abl gene in a chronic myeloid leukemia patient.

PMID- 30118901
TI  - Ribociclib plus letrozole and concomitant palliative radiotherapy for metastatic
      breast cancer.
AB  - Ribociclib is a CDK4-6 inhibitor recently approved by the Food and Drug
      Administration (FDA) and the European Medicines Agency (EMA) as first-line
      treatment for metastatic breast cancer (MBC). The pivotal trial showed a
      significant improvement in progression-free survival when compared to endocrine
      therapy alone. However, having a challenging toxicity profile in comparison with
      exclusive endocrine therapy, safety may be a concern when combined to
      radiotherapy (RT) with palliative approach. There are no available published data
      regarding the combination of ribociclib and palliative RT. We reported our
      preliminary experience on the first five patients treated at the Radiation
      Oncology Unit of the Florence University (Florence, Italy) giving palliative RT
      concomitant to ribociclib plus letrozole as first-line treatment for MBC.

PMID- 30118899
TI  - Antiphospholipid syndrome: An update on risk factors for pregnancy outcome.
AB  - BACKGROUND: The optimal treatment of women with primary antiphospholipid syndrome
      (APS) is still debated. About 20-30% of women with APS remain unable to give
      birth to healthy neonates despite conventional treatment, consisting of
      prophylactic-dose heparin and low-dose aspirin. These cases are defined
      "refractory obstetric APS". The early identification of risk factors associated
      with poor pregnancy outcome could be the optimal strategy to establish criteria
      for additional therapies, such as hydroxychloroquine, steroids, intravenous
      immunoglobulin, and plasma exchange. PURPOSE: The aim of the present study was to
      review current literature about risk factors for poor pregnancy outcome. SEARCH
      METHODS: The PubMed database was used to search for peer-reviewed original and
      review articles concerning risk factors for pregnancy outcome in APS from 1st
      January 1990 to 15th January 2018. OUTCOMES: History of pregnancy morbidity
      and/or thrombosis, the association with SLE and/or other autoimmune diseases are
      well known history-based predictive factors for obstetrical complications, such
      as miscarriage, maternal venous thromboembolism, intrauterine foetal demise,
      preeclampsia, and neonatal death. Moreover, laboratory findings associated with
      poor pregnancy outcome are:triple antiphospholipid antibodies aPL positivity,
      double aPL positivity, single aPL positivity, false-positive IgM for CMV, and
      hypocomplementemia. Triple positivity is confirmed as the most significant risk
      factor by a large body of evidence. Furthermore, the abnormal uterine arteries
      Doppler velocimetry results are confirmed to be strongly associated with poor
      pregnancy outcomes in APS. The good performance of the uterine arteries
      velocimetry, as a negative predictive factor, was reported by different studies.
      On the contrary, in case of abnormal uterine arteries results, the relevance of a
      careful surveillance is highlighted for the high risk of maternal-foetal
      complications. Nevertheless, this tool is a late indicator to suggest any
      additional treatments. CONCLUSIONS: In order to prevent obstetrical complications
      and establish the optimal combination therapy, the knowledge at preconception or
      at the beginning of pregnancy of risk factors associated with poor pregnancy
      outcome could be a crucial step for management and treatment of APS. In addition,
      in the preconception assessment a regimen with low-dose aspirin, folic acid, and
      vitamin D supplementation should be offered, and a treatment strategy has to be
      established (conventional vs additional therapy). In fact, additional treatment
      has to be tailored for each patient.

PMID- 30118902
TI  - Breast-conserving therapy for primary Ductal Carcinoma in Situ in The
      Netherlands: A multi-center study and population-based analysis.
AB  - OBJECTIVE: The aim of this study was to analyse the efficacy of breast-conserving
      therapy (BCT) for women with primary DCIS in a population-based setting. METHODS:
      Data were used from five Radiotherapy centres in The Netherlands from 2000 to
      2010, all treated with BCT. Of all the cases, 59.2% received a boost of
      radiotherapy after their whole breast irradiation (WBI), irrespective of margin
      status. RESULTS: A total of 1248 cases with primary DCIS were analysed. The 10
      years LRFS was 92.9%. Age <=50 years and a positive margin were significantly
      related to local relapse free survival (LRFS). Having a boost had no impact on
      LRFS, showing a nearly equal recurrence pattern in patients with and without a
      boost. Separate analyses were done on patients who had received and not received
      a boost of radiotherapy after WBI. We noted 9.1% contra-lateral breast tumours.
      The 10-years disease specific survival (DSS) rate was 99.0%. CONCLUSIONS: DCIS of
      the breast and treated with BCT results in excellent LRFS and DSS. Primary
      surgical lumpectomy with negative margins followed by WBI seems to be the
      treatment of choice in DCIS treated with BCS with respect to IBTR.

PMID- 30118900
TI  - The role of stress in the mosaic of autoimmunity: An overlooked association.
AB  - Stress is defined as the pscyophysiological reaction in which the steady state is
      disturbed or threatened. Stress is not always perceived as a negative response.
      Stress results when environmental demands exceed an individuals' adaptive
      capacities. Autoimmune diseases are heterogeneous group of chronic diseases which
      occur secondary to loss of self antigen tolerance. The etiopathogenesis of
      autoimmune disease is uncertain. Genetic factors as well as environmental factors
      appear to interplay, leading to a cascade of events resulting in disease onset.
      Stress has been postulated to play a role in disease onset in the genetically
      susceptible patients. During the stress response, catecholamines and
      glucocorticoids are released from locus coeruleus and adrenal gland. These
      biomolecules exert control over various immune cells in the innate and adaptive
      arms of the immune system, thereby altering the cytokine profile released. The
      increase of IL-4 promotes T-helper 2 (Th2) cell differentiation, while the
      decrease in IL-12 and the increased IL-10 production reduce the number of T
      helper 1 (Th1) cells. The relationship between stress and autoimmune diseases is
      intricate. Stress has been shown to be associated with disease onset, and disease
      exacerbations in rheumatoid arthritis, systemic lupus erythematosus, inflammatory
      bowel disease, multiple sclerosis, Graves' disease as well as other autoimmune
      conditions. In certain conditions such as psoriasis, stress has been implicated
      in delaying lesion clearance upon the application of standard treatment regimes.
      Finally, psychological therapy and cognitive behavioral therapy aimed to reduce
      stress levels was shown to be effective in influencing better outcomes in many
      autoimmune diseases. The purpose of this paper is to closer inspect the clinical
      evidence regarding the role of stress on influencing the various aspects of
      disease entities.

PMID- 30118903
TI  - ALA-PDT promotes HPV-positive cervical cancer cells apoptosis and DCs maturation
      via miR-34a regulated HMGB1 exosomes secretion.
AB  - 5-Aminolevulinic acid photodynamic therapy(ALA-PDT) has been widely used for
      cervical cancer treatment, but the mechanisms are still not fully delineated.
      Here we showed that ALA-PDT significantly upregulated HMGB1 while downregulated
      miR-34a expression levels in cervical cancer tissues, and the percentages of
      mature DCs(mDCs) were increased in ALA-PDT treated patients' peripheral blood.
      After treating HPV-positive Hela, SiHa, Caski and HPV-negative C33 A cervical
      cancer cell lines with ALA-PDT, HPV-positive cells' proliferative ability was
      significantly inhibited and apoptosis rates were elevated, while no significant
      changes were found in HPV-negative C33 A cell line. Most importantly, in HPV
      positive cells, we found that miR-34a were downregulated in cytoplasm, and both
      cytoplasm and exosome HMGB1 were significantly elevated comparing to cancer cells
      without ALA-PDT treatment, and it could be reversed by miR-34a mimic
      transfection, which indicated that HPV infection and miR-34a downregulation might
      be vital for ALA-PDT treatment. Based on the HMGB1 is the potential target of miR
      34a and an inverse correlation between miR-34a and HMGB1 in ALA-PDT treated
      cancer tissues, we verified that HMGB1 could be targeted and downregulated by miR
      34a mimic, and ALA-PDT promotes HMGB1 secretion by inhibiting miR-34a expression.
      By co-culturing cervical cancer cell lines with immature DCs(imDCs) in the
      Transwell systems, we found that ALA-PDT induced HMGB1 exosomes could promote DCs
      maturation, which could be reversed by silencing HMGB1 in HPV-positive cervical
      cancer cells. In vivo animal experiments also proved that ALA-PDT inhibited tumor
      growth in tumor bearing mice, which was reversed by co-transfected with miR-34a
      mimic or silencing HMGB1 in HPV-positive cells. Hence we concluded that ALA-PDT
      treatment specifically inhibited HPV-positive cervical cancer cells'
      proliferative ability, promoted cell apoptosis and modulated DCs maturation by
      regulating miR-34a mediated HMGB1 exosomes secretion.

PMID- 30118904
TI  - The effects of hybrid light activation and enamel acid etching on the
      effectiveness, stability and sensitivity after a single session in-office
      bleaching: A 12-month clinical trial.
AB  - BACKGROUND: The use of hybrid-light (HL) during in-office teeth bleaching can
      provide faster and reliable results after a single bleaching session, especially
      if associated with previous acid etching. The present in vivo, interventional,
      split-mouth, triple-blinded and randomized study evaluated the efficiency of a
      HL, with and without prior enamel acid etching, assessing the gel application
      time, degree of color change, sensitivity and treatment stability up to 12
      months. METHODS: Thirty-four patients were selected and randomly divided into
      four groups. The color was evaluated using a spectrophotometer with the CIELab
      color system, and a VAS questionnaire was used to evaluate the sensitivity. Both
      upper and lower hemiarches (GI and III) received enamel acid etching with 37%
      phosphoric acid for 15 s prior to the application of 35% hydrogen peroxide gel
      (HP). For GI and II, HP was applied on both dental arches for 3-4 consecutive
      applications and activated by HL (2 * 3' activations with 1' interval); and 3 *
      15' (HP) for GIII and IV without HL. Patients returned in 24 h, 1 week, 1-, 6-
      and 12-months intervals. The clinical operator was different from the clinical
      measurements operator. RESULTS: After 3-way ANOVA, Tukey's, Wilcoxon and Mann
      Whitney tests, all with p < 0.05, no statistical differences were observed
      between the groups regarding color change (DeltaE) and sensitivity in all
      evaluations. The lowest gel application time was observed for GII (acid etch +
      HL), followed by GI (HL). CONCLUSIONS: The present study's results reveal the
      advantages of HL associated with acid etching prior to in office bleaching.

PMID- 30118905
TI  - Photodynamic therapy for rosacea in Chinese patients.
AB  - BACKGROUND: Rosacea is a common chronic cutaneous disorder which is characterized
      by flushing, erythema, papulopustules and telangiectasia. The pathogenesis of the
      disease is still unknown. A multifaceted approach is necessary to control the
      disease because of its tendency to relapse. New more effective treatment options
      are desirable to achieve a complete remission. Aminolevulinic acid-photodynamic
      therapy (ALA-PDT) is a well-established treatment for non-melanoma skin cancer
      and precancerous lesions. ALA- PDT can also be used for inflammatory disease,
      including acne vulgaris. However, little is known about the efficacy and safety
      of ALA-PDT for rosacea in Chinese patients with Fitzpatrick skin types III and
      IV. OBJECTIVES: To investigate the efficacy and safety of ALA-PDT in the
      treatment of rosacea classified as erythematotelangiectatic type or
      papulopustular type. METHODS: Twenty rosacea patients with either
      erythematotelangiectatic or papulopustular types were enrolled. 5% 5
      Aminolevulinic acid in an oil-in-water emulsion was applied to the lesions under
      occlusion with plastic film for 2 h, and the lesions were irradiated with 100
      mW/cm2, 80-90 J/cm2, LED red light (635 +/- 15 nm) over 15 min in each session
      with four sessions at 10-day intervals. Objective measures (severity of flushing,
      erythema and telangiectasia, number of inflammatory lesions, VISIA Red Complexion
      Analysis images), subjective symptoms (including itching, prickling, burning,
      etc.) were recorded at baseline and at 4, 12 and 24 weeks after the last
      treatment. Adverse effects were recorded at each treatment and follow-up visit.
      RESULTS: During the follow-up period, all patients showed gradual objective
      clinical improvement compared with baseline (P < 0.01). Clinical inflammatory
      lesions disappeared completely in all patients after 24 weeks. Subjective
      symptoms, including flushing, itching, prickling, burning et al, had vanished and
      did not show any relapse during the follow-up period. The main side effects of
      ALA-PDT were pain, erythema, swelling and post- inflammatory hyperpigmentation.
      All side-effects were transient and tolerated by all the patients. No patients
      were dissatisfied with the therapeutic outcome. CONCLUSIONS: ALA-PDT is an
      effective and safe approach for the treatment of rosacea of
      erythematotelangiectatic or papulopustular types, to control clinical
      manifestations and reduce subjective symptoms.

PMID- 30118906
TI  - Hypericin-assisted photodynamic therapy against anaplastic thyroid cancer.
AB  - BACKGROUND: Hypericin (HYP) extracted from St. John's wort (Hypericum perforatum
      L.) is a natural photosensitizer in clinical photodynamic therapy (PDT). PDT is
      one of the powerful methods for cancer treatments because of its excellent
      tumoritropic characteristics and photosensitizing properties. However, limited
      reports on the efficacy of PDT on anaplastic thyroid cancer (ATC) have been
      published. Especially HYP-associated PDT has not been investigated in vitro and
      in vivo. In this study, we evaluated the effect of HYP for PDT against FRO ATC
      cells. METHODS: The activities of HYP-assisted PDT were investigated in ATC
      cells. The ATC FRO cells were treated with a combination of HYP dose and laser
      power. The viability of FRO cells was measured by MTT assay, and Trypan blue
      staining was performed to monitor cell death. Detection reactive oxygen species
      (ROS) and mitochondrial membrane potential after HYP-assisted PDT were analyzed
      by confocal microscopy. For in vivo study, FRO cells were injected into nude
      mice. After intravenous injection of HYP, Laser was irradiated and nude mice were
      monitored in Day 4, 7, 14. RESULTS AND CONCLUSIONS: The rate of FRO cell death
      was increased by applying HYP dose and laser power dependent. Moreover, HYP and
      laser irradiation induced FRO cell death was mediated by the intracellular ROS
      generation and mitochondrial damage. Finally, the HYP-assisted PDT eliminated FRO
      cell tumor from the mouse in vivo. These data demonstrate that HYP could be an
      effective photosensitizer for human ATC therapy.

PMID- 30118907
TI  - Linking the contents of hydrophobic PAHs with the canopy water storage capacity
      of coniferous trees.
AB  - The canopy water storage capacity (S) is an important parameter for the
      hydrological cycle in forests. One factor which influences the S is leaf texture,
      which in turn is thought to be affected by the contents of polycyclic aromatic
      hydrocarbons (PAHs). In order to improve our understanding of S we simulated
      rainfall and measured the S of coniferous species growing under various
      conditions. The contents of 18 PAHs were measured in the needles. The species
      chosen were: Scots pine (Pinus sylvestris L), Norway spruce (Picea abies (L.) H.
      Karst) and silver fir (Abies Alba Mill.). Sample branches were collected in 3
      locations: A - forest; B - housing estate; C - city center. We found that PAHs
      have a significant impact on the S of tree crowns. The increase in the total
      content of all of polycyclic aromatic hydrocarbons (SUM.PAH) translates into an
      increase of S for all species. The S is the highest for the P. abies species,
      followed by P. sylvestris and A. alba at all locations. Within the same species,
      an increase in the value of S is associated with an increase in the PAH content
      in needles measured by gas chromatography. For A.alba, the average S increased
      from 11.54% of the total amount of simulated rain (ml g-1) at location A, to
      17.10% at location B, and 21.02% at location C. Similarly for P. abies the S was
      21.78%, 29.06% and 34.36% at locations A, B and C respectively. The study extends
      the knowledge of the mechanisms of plant surface adhesion and the anthropogenic
      factors that may modify this process as well as foliage properties.

PMID- 30118908
TI  - Metals content of recycled construction and demolition wood before and after
      implementation of best management practices.
AB  - A limitation to recycling wood from construction and demolition (C&D) waste is
      contamination of metals from the inadvertent inclusion of preservative treated
      wood, in particular wood treated with chromated copper arsenate (CCA) and newer
      copper-based formulations. To minimize contamination many regions have developed
      best management practices (BMPs) for separating treated from untreated wood. The
      objective of this study was to evaluate the fraction of preservative treated wood
      in recycled C&D wood after the implementation of BMPs, using Florida as a case
      study. Methods involved collecting recycled C&D wood samples from throughout the
      state, measuring metals concentrations (As, Cu, and Cr) in the samples to compute
      the fraction of recycled wood treated with waterborne wood preservatives, and
      comparing measurements with those taken prior to the formalization of BMPs.
      Metals concentrations were measured using two methods, one based on traditional
      laboratory digestion methods and another using a more rapid hand-held X-ray
      Fluorescence (XRF) device in the field. The proportion of waterborne preservative
      treated wood in recycled wood products has reduced significantly in the
      intervening 20 years (from 6% to 2.9%), and the fraction of CCA-treated wood has
      been reduced even further, to 1.4%. The remaining fraction of waterborne
      preservative-treated wood is comprised of new formulations of copper-based
      preservatives. This suggests that restrictions from the wood preservation
      industry and best management practices implemented at recycling facilities have
      been effective in reducing heavy metal contamination from pressure treated lumber
      in recycled wood products.

PMID- 30118909
TI  - Influence of extracellular polymeric substances on cell-NPs heteroaggregation
      process and toxicity of cerium dioxide NPs to Microcystis aeruginosa.
AB  - The presence of abundant extracellular polymeric substances (EPS) play a vital
      role in affecting heteroaggregation process and toxicity of nanoparticles (NPs)
      to Microcystis aeruginosa. Interactions between n-CeO2 and cyanobacteria
      with/without EPS and the toxicity of n-CeO2 to M. aeruginosa were investigated in
      this study. Aggregation kinetics of n-CeO2 under both soluble EPS (SEPS) and
      bound EPS (BEPS) indicated the presence of EPS could induced the formation of EPS
      NPs aggregates. Heteroaggregation between cells and n-CeO2 was confirmed through
      co-settling experiment and SEM-EDS observation. SEPS contributed to the
      observable heteroaggregation using spectral measurement. Heteroaggregation
      between cells and n-CeO2 under no BEPS was hardly obtained through spectral
      measurement, but SEM-EDS observation convinced this process. And the DLVO theory
      explained this heteroaggregation process under various EPS conditions, where the
      energy barrier decreased with gradual EPS extraction. In addition, the order for
      96 h half growth inhibition concentration (IC50) was Raw M9 > M9-SEPS > M9+BEPS >
      M9-BEPS. These results revealed that not all heteroaggregation between cell-NPs
      can lead to the NPs toxicity to cells. BEPS act more important role in buffering
      against the toxicity of NPs from ambient adverse factors, but SEPS increase the
      stability of NPs which could aggravate the adverse effects of NPs in the
      environment.

PMID- 30118910
TI  - Nanoplastics impaired oyster free living stages, gametes and embryos.
AB  - In the marine environment, most bivalve species base their reproduction on
      external fertilization. Hence, gametes and young stages face many threats,
      including exposure to plastic wastes which represent more than 80% of the debris
      in the oceans. Recently, evidence has been produced on the presence of
      nanoplastics in oceans, thus motivating new studies of their impacts on marine
      life. Because no information is available about their environmental
      concentrations, we performed dose-response exposure experiments with polystyrene
      particles to assess the extent of micro/nanoplastic toxicity. Effects of
      polystyrene with different sizes and functionalizations (plain 2-MUm, 500-nm and
      50-nm; COOH-50 nm and NH2-50 nm) were assessed on three key reproductive steps
      (fertilization, embryogenesis and metamorphosis) of Pacific oysters (Crassostrea
      gigas). Nanoplastics induced a significant decrease in fertilization success and
      in embryo-larval development with numerous malformations up to total
      developmental arrest. The NH2-50 beads had the strongest toxicity to both gametes
      (EC50 = 4.9 MUg/mL) and embryos (EC50 = 0.15 MUg/mL), showing functionalization
      dependent toxicity. No effects of plain microplastics were recorded. These
      results highlight that exposures to nanoplastics may have deleterious effects on
      planktonic stages of oysters, presumably interacting with biological membranes
      and causing cyto/genotoxicity with potentially drastic consequences for their
      reproductive success.

PMID- 30118911
TI  - Photodegradation of 17beta-estradiol on silica gel and natural soil by UV
      treatment.
AB  - This paper evaluates the UV photodegradation of 17beta-estradiol (E2) on silica
      gel and in natural soil with different soil components. Silica gel was chosen as
      a stable and pure support to simulate the photochemical behavior of E2 on the
      surface of natural soil. Ultraviolet light, rather than visible light, was
      confirmed to play a decisive role in the photodegradation of E2 on silica gel.
      The effect of three soil components, including humic acid (HA), inorganic salts,
      and relative humidity (RH), on the photochemical behavior of E2 on silica gel or
      soil under UV irradiation was then evaluated. Two HA concentrations (10 and 20 mg
      g-1) and three salts (ferric sulfate, copper sulfate and sodium carbonate) were
      observed to obviously inhibit the degradation of E2 on silica gel. Interestingly,
      nitrate was found to obviously improve the removal efficiency of E2. Both too-dry
      and too-wet conditions obviously reduced the removal rate of E2, and the optimum
      relative humidity (RH) value was found to be approximately about 35% (30  degrees
      C). Furthermore, twenty intermediate products and two major pathways were
      proposed to describe the transformation processes of E2 treated by UV
      irradiation, among which oligomers were found to be the major intermediate
      products before complete mineralization. The efficient UV removal of E2 on silica
      gel and natural soil suggested a feasible strategy to remediate E2 contaminated
      soil.

PMID- 30118912
TI  - Evaluation of the leaching of florfenicol from coated medicated fish feed into
      water.
AB  - Florfenicol is one of the most-used antimicrobial agents in global fish farming.
      Nevertheless, in most countries, its use is not conducted in accordance with good
      practices. The aim of this work was to evaluate the leaching of florfenicol from
      coated fish feed into the water. Analytical methods were developed and validated
      for the quantitation of florfenicol in medicated feed and water by UHPLC-MS/MS.
      Florfenicol residues in the water were quantified after 5- and 15-min exposures
      of the medicated feed in the water at 22 and 28  degrees C and at pH 4.5 and 8.0.
      The influence of pellet size and three coating agents (vegetable oil,
      carboxymethylcellulose, and low-methoxylated pectin) on the leaching of the drug
      was also assessed. Pellet size, coating agent, water temperature, and time of
      exposure significantly (p < 0.05) affected florfenicol leaching, while water pH
      did not interfere with the leaching. Coating with vegetable oil was the most
      efficient method to reduce florfenicol leaching, while coating with
      carboxymethylcellulose presented the highest leaching (approximately 60% after 15
      min at 28  degrees C). Thus, the coating agent has a significant effect on the
      florfenicol leaching rate and, consequently, on the necessary dose of the drug to
      be administered. Moreover, it is worth mentioning that higher florfenicol
      leaching will pose a greater risk to environmental health, specifically in terms
      of the development of bacteria resistant to florfenicol. Additional studies are
      needed with other polymers and veterinary drugs used in medicated feed for fish
      farming.

PMID- 30118913
TI  - Seasonal and spatial variations of biomarker responses of rock oysters in a
      coastal environment influenced by large estuary input.
AB  - The present study assessed the spatial and temporal variations and the potential
      influences of the Pearl River discharge on trace metal bioaccumulation and
      biomarker responses in Hong Kong coastal waters. A suite of biomarkers including
      antioxidant defense, oxidative stress, metal detoxification, cellular response,
      neurotoxicity, and energy reserve were quantified in the rock oyster Saccostrea
      cucullata over spatial scale across the east and west of Hong Kong. We documented
      the elevated Cd, Cu and Zn concentrations in all western stations in the fall
      season, as a result of time-integrated accumulation during the peak discharge of
      the Pearl River Estuary (PRE) in summer. Lipid peroxidation and total glutathione
      corresponded well with the overall metal gradient and showed significant
      correlation with the tissue Cu bioaccumulation. The eastern station (Clear Water
      Bay) also exhibited high Cd and Cu concentrations with increased oxidative stress
      responses. In the spring, metal bioaccumulation in the oysters was reduced due to
      the weakened influence of PRE, with correspondingly less obvious biomarker
      responses. Our coupling measurements of biomarkers and tissue metal
      concentrations for the first time revealed that the large PRE could have latent
      and seasonal biological effects on the Hong Kong coastal biota. Sensitive
      biomarkers such as lipid peroxidation and glutathione responses might be good
      candidates for detecting the early biological responses in such sub-lethal
      contaminated environments.

PMID- 30118914
TI  - IL-36gamma induces a transient HSV-2 resistant environment that protects against
      genital disease and pathogenesis.
AB  - Herpes simplex virus 2 (HSV-2) causes a persistent, lifelong infection that
      increases risk for sexually transmitted infection acquisition. Both the lack of a
      vaccine and the need for chronic suppressive therapies to control infection
      presents the need to further understand immune mechanisms in response to acute
      HSV-2 infection. The IL-36 cytokines are recently identified members of the IL-1
      family and function as inflammatory mediators at epithelial sites. Here, we first
      used a well-characterized three-dimensional (3-D) human vaginal epithelial cell
      (VEC) model to understand the role of IL-36gamma in the context of HSV-2
      infection. In 3-D VEC, IL-36gamma is induced by HSV-2 infection, and pretreatment
      with exogenous IL-36gamma significantly reduced HSV-2 replication. To assess the
      impact of IL-36gamma treatment on HSV-2 disease pathogenesis, we employed a
      lethal genital infection model. We showed that IL-36gamma treatment in mice prior
      to lethal intravaginal challenge significantly limited vaginal viral replication,
      delayed disease onset, decreased disease severity, and significantly increased
      survival. We demonstrated that IL-36gamma treatment transiently induced pro
      inflammatory cytokines, chemokines, and antimicrobial peptides in murine lower
      female reproductive tract (FRT) tissue and vaginal lavages. Induction of the
      chemokines CCL20 and KC in IL-36gamma treated mice also corresponded with
      increased polymorphonuclear (PMN) leukocyte infiltration observed in vaginal
      smears. Altogether, these studies demonstrate that IL-36gamma drives the
      transient production of immune mediators and promotes PMN recruitment in the
      vaginal microenvironment that increases resistance to HSV-2 infection and
      disease. Our data indicate that IL-36gamma may participate as a key player in
      host defense mechanisms against invading pathogens in the FRT.

PMID- 30118915
TI  - Acute infection with Strongyloides venezuelensis increases intestine production
      IL-10, reduces Th1/Th2/Th17 induction in colon and attenuates Dextran Sulfate
      Sodium-induced colitis in BALB/c mice.
AB  - Helminth infection can reduce the severity of inflammatory bowel disease.
      However, the modulatory mechanisms elicited by helminth infection are not yet
      fully understood and vary depending on the experimental model. Herein we
      evaluated the effect of acute infection of BALB/c mice with Strongyloides
      venezuelensis on the clinical course of ulcerative colitis induced by Dextran
      Sulfate Sodium (DSS) treatment of these animals. For the experiments, S.
      venezuelensis-infected BALB/c mice were treated orally with 4% DSS solution for
      seven days. As controls, we used untreated S. venezuelensis infected, DSS-treated
      uninfected, and untreated/uninfected BALB/c mice. During DSS treatment, mice from
      the different groups were compared with regards to the clinical signs related to
      the severity of colitis and intestinal inflammation. Mice acutely infected with
      S. venezulensis and treated with DSS had reduced clinical score, shortening of
      the colon, and tissue inflammation. Moreover, DSS-treated and infected mice
      showed reduced IL-4, INF-gamma, and IL-17 levels and increase of IL-10 production
      in the colon and/or in the supernatant of mesenteric lymph nodes cell cultures
      that resulted in lower eosinophil peroxidase and myeloperoxidase activity in
      colon homogenates, when compared with DSS-treated uninfected mice. DSS-treated
      infected mice also preserved the intestine architecture and had normal
      differentiation of goblet cells and mucus production in the colon mucosa. In
      conclusion, the data indicate that the clinical improvement reported in DSS
      treated infected mice was accompanied by the lower production of Th1/Th2/Th17 pro
      inflammatory cytokines, stimulation of IL-10, and induction of mucosal repair
      mechanisms.

PMID- 30118916
TI  - Seasonality of respiratory viruses causing hospitalizations for acute respiratory
      infections in children in Nha Trang, Vietnam.
AB  - BACKGROUND: Acute respiratory infections (ARIs) are the most common causes of
      death in children under 5 years of age. While the etiology of most pneumonia and
      ARI episodes is undiagnosed, a broad range of ARI-causing viruses circulate
      widely in South East Asia. However, the patterns and drivers of the seasonal
      transmission dynamics are largely unknown. Here we identify the seasonal patterns
      of multiple circulating viruses associated with hospitalizations for ARIs in Nha
      Trang, Vietnam. METHODS: Hospital based enhanced surveillance of childhood ARI is
      ongoing at Khanh Hoa General Hospital in Nha Trang. RT-PCR was performed to
      detect 13 respiratory viruses in nasopharyngeal samples from enrolled patients.
      Seasonal patterns of childhood ARI hospital admissions of various viruses were
      assessed, as well as their association with rainfall, temperature, and dew point.
      RESULTS: Respiratory syncytial virus peaks in the late summer months, and
      influenza A in April to June. We find significant associations between detection
      of human parainfluenza 3 and human rhinovirus with the month's mean dew point.
      Using a cross-wavelet transform we find a significant out-of-phase relationship
      between human parainfluenza 3 and temperature and dew point. CONCLUSIONS: Our
      results are important for understanding the temporal risk associated with
      circulating pathogens in Southern Central Vietnam. Specifically, our results can
      inform timing of routing seasonal influenza vaccination and for when observed
      respiratory illness is likely viral, leading to judicious use of antibiotics in
      the region.

PMID- 30118918
TI  - Interventions for involuntary psychiatric inpatients: A systematic review.
AB  - BACKGROUND: Observational research has found that involuntary treatment provides
      limited benefits in terms of long-term clinical outcomes. Our aim was to review
      literature on existing interventions in order to identify helpful approaches to
      improve outcomes of involuntary treatment. METHODS: This systematic review
      follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses
      (PRISMA) statement guidelines. Seven databases (AMED, PsycINFO, Embase Classic,
      Embase 1974-2017, CINAHL, MEDLINE, and BNI) were searched and the results were
      analysed in a narrative synthesis. RESULTS: Nineteen papers describing fourteen
      different interventions were included. Using narrative synthesis the
      interventions were summarised into three categories: a) structured patient
      centred care planning; b) specialist therapeutic interventions; c) systemic
      changes to hospital practice. The methodologies used and outcomes assessed were
      heterogeneous. Most studies were of low quality, although five interventions were
      tested in randomised controlled trials (RCTs). Preliminary evidence supports
      structured patient-centred care planning interventions have an effect on long
      term outcomes (such as readmission), and that specialist therapeutic
      interventions and systemic changes to hospital practice have an effect on
      reducing the use of coercive measures on wards. CONCLUSIONS: This review shows
      that it is possible to conduct rigorous intervention-testing studies in
      involuntary patients, including RCTs. Yet, the overall evidence is limited.
      Structured patient-centred care planning interventions show promise for the
      improvement of long-term outcomes and should be further evaluated.

PMID- 30118917
TI  - How to improve clinical practice on forced medication in psychiatric practice:
      Suggestions from the EUNOMIA European multicentre study.
AB  - BACKGROUND: The decision to adopt forced medication in psychiatric care is
      particularly relevant from a clinical and ethical viewpoint. The European
      Commission has funded the EUNOMIA study in order to develop European
      recommendations for good clinical practice on coercive measures, including forced
      medication. METHODS: The recommendations on forced medication have been developed
      in 11 countries with the involvement of national clinical leaders, key
      professionals and stakeholders' representatives. The national recommendations
      have been subsequently summarized into a European shared document. RESULTS:
      Several cross-national differences exist in the use of forced medication. These
      differences are mainly due to legal and policy making aspects, rather than to
      clinical situations. In fact, countries agreed that forced medication can be
      allowed only if the following criteria are present: 1) a therapeutic intervention
      is urgently needed; 2) the voluntary intake of medications is consistently
      rejected; 3) the patient is not aware of his/her condition. Patients' dignity,
      privacy and safety shall be preserved at all times. CONCLUSION: The results of
      our study show the need of developing guidelines on the use of forced medication
      in psychiatric practice, that should be considered as the last resort and only
      when other therapeutic option have failed.

PMID- 30118919
TI  - Pharmacological treatment for REM sleep behavior disorder in Parkinson disease
      and related conditions: A scoping review.
AB  - Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia
      characterized by the presence of a complex of signals resulting from the loss of
      REM sleep atony and manifested by vigorous and sometimes violent motor jerks and
      nocturnal vocalizations associated with dream enactment. RBD might be a clinical
      predictor of severity for Parkinson's disease (PD) and one of its most important
      non-motor manifestations, preceding the emergence of synucleinopathy by several
      years or even decades. The detection of RBD may represent a therapeutic window
      for research regarding the development of new neuroprotective therapies with the
      potential to modify the natural course of synucleinopathies, such as PD. We
      performed a scoping review of studies indexed in MEDLINE and LILACS focusing on
      pharmacological interventions for RBD associated with PD. Fourteen articles were
      selected. Study designs comprised randomized and non-randomized clinical trials
      (n = 153 participants) and observational studies (retrospective cohorts and case
      series, n = 248 participants). Melatonin and clonazepam appear to be useful for
      treating RBD in PD, but these findings are mostly supported by observational
      studies and a few controlled studies with a small number of participants. New
      pharmacological agents, such as melatoninergic agonists and phytocannabinoids,
      appear to be promising therapies. The findings from studies focusing on
      anticholinesterases and new dopaminergic agents are still deemed inconclusive.

PMID- 30118920
TI  - A method for investigating the cellular response to cyclic tension or compression
      in three-dimensional culture.
AB  - We have an interest in the cellular response to mechanical stimuli, and here
      describe an in-vitro method to examine the response of cells cultured in a three
      dimensional matrix to mechanical compressive and tensile stress. Synthetic
      aliphatic polyester scaffolds coated with 45S5 bioactive glass were seeded with
      human dental follicular cells (HDFC), and attached to well inserts and magnetic
      endplates in six well palates. Scaffolds were subjected to either cyclic 10%
      tensile deformation, or 8% compression, at 1 Hz and 2 Hz respectively for 6, 24
      or 48 h, by uniaxial motion of magnetically-coupled endplates. It was possible to
      isolate high quality mRNA from cells in these scaffolds, as demonstrated by high
      RNA integrity numbers scores, and ability to perform meaningful cRNA microarray
      analysis, in which 669 and 727 genes were consistently upregulated, and 662 and
      518 genes down regulated at all times studied under tensile and compressive
      loading conditions respectively. MetaCore analysis revealed the most regulated
      gene ontogenies under both loading conditions to be for: cytoskeletal
      remodelling; cell adhesion-chemokines and adhesion; cytoskeleton remodelling-TGF
      WNT and cytoskeletal remodelling pathways. We believe the method here described
      will be of value for analysis of the cellular response to cyclic loading.

PMID- 30118922
TI  - Obesity, perceived weight discrimination, and hair cortisol: a population-based
      study.
AB  - BACKGROUND AND PURPOSE: Stigmatization of individuals with obesity is pervasive
      and may act as a psychological stressor. The present study examined whether
      perceived weight discrimination mediated the relationship between obesity and
      cortisol, an objective marker of chronic stress, in a population-based sample.
      METHODS: Data were from the English Longitudinal Study of Ageing (n = 1872).
      Height and weight were objectively measured in 2008/09. Experiences of weight
      related discrimination were reported via questionnaire in 2010/11. Hair cortisol
      concentrations were determined from the scalp-nearest 2 cm hair segment in
      2012/13. Mediation analyses tested the role of perceived weight discrimination in
      the associations between obesity and BMI and hair cortisol concentration,
      adjusting for age, sex, ethnicity, socio-economic status, smoking status,
      depression and hair-related factors. RESULTS: Obesity, BMI and perceived weight
      discrimination were positively related to hair cortisol (all p <  .01). Perceived
      weight discrimination significantly mediated associations between obesity and
      hair cortisol (beta = 0.021, SE = 0.007, 95% CI 0.007-0.036) and BMI and hair
      cortisol (beta = 0.001, SE = 0.0004, 95% CI 0.0004-0.002), accounting for 19% of
      the total effect of obesity and 23% of the total effect of BMI on hair cortisol.
      CONCLUSIONS: Perceived weight discrimination is an important mediator of the
      association between obesity and cortisol. Interventions combating weight stigma
      and discrimination or promoting strategies for coping with stress could help to
      lessen the psychological and physiological burden of obesity.

PMID- 30118921
TI  - Biomechanical properties and microstructure of neonatal porcine ventricles.
AB  - Neonatal heart disorders represent a major clinical challenge, with congenital
      heart disease alone affecting 36,000 new-borns annually within the European
      Union. Surgical intervention to restore normal function includes the implantation
      of synthetic and biological materials; however, a lack of experimental data
      describing the mechanical behaviour of neonatal cardiac tissue is likely to
      contribute to the relatively poor short- and long-term outcome of these implants.
      This study focused on characterising the mechanical behaviour of neonatal cardiac
      tissue using a porcine model, to enhance the understanding of how this differs to
      the equivalent mature tissue. The biomechanical properties of neonatal porcine
      cardiac tissue were characterised by uniaxial tensile, biaxial tensile, and
      simple shear loading modes, using samples collected from the anterior and
      posterior walls of the right and left ventricles. Histological images were
      prepared using Masson's trichrome staining, to enable assessment of the
      microstructure and correlation with tissue behaviour. The mechanical tests
      demonstrated that the neonatal cardiac tissue is non-linear, anisotropic,
      viscoelastic and heterogeneous. Our data provide a baseline describing the
      biomechanical behaviour of immature porcine cardiac tissue. Comparison with
      published data also indicated that the neonatal porcine cardiac tissue exhibits
      one-half the stiffness of mature porcine tissue in uniaxial extension testing,
      one-third in biaxial extension testing, and one-fourth stiffness in simple shear
      testing; hence, it provides an indication as to the relative change in
      characteristics associated with tissue maturation. These data may prove valuable
      to researchers investigating neonatal cardiac mechanics.

PMID- 30118923
TI  - Nutritional Intake by Ectoplasmic Nets of Schizochytrium aggregatum
      (Labyrinthulomycetes, Stramenopiles).
AB  - Thraustochytrid cells attach to their food via ectoplasmic nets (ENs). Here, we
      analyzed the cause and effect relationship between the various forms and
      functions of ENs of Schizochytrium aggregatum. The ENs spread out over a large
      area forming a fine network to efficiently search for the experimental food
      source. After recognizing the experimental food source, the ENs that attached to
      the food source became thicker, and net elements developed. The thick ENs on the
      surface at the attachment site were enveloped in dense materials (fibrous
      materials), which were visualized as fibrous layers under a transmission electron
      microscope. Experiments using fluorescein diacetate and the fluorescent glucose
      analog 2-NBDG showed that the production rate of hydrolytic enzymes and the
      absorption rate of glucose by ENs of S. aggregatum increased in the presence of
      an experimental food source. Our results reveal that ENs change their shape and
      function according to the presence/absence of a food source.

PMID- 30118924
TI  - Longitudinal changes in comorbidity patterns over time in relation to mortality
      in older Korean adults.
AB  - This study investigates the different pattern of change in comorbidity over time
      and its effect on mortality in older adults in South Korea. Data are from the
      National Health Insurance Service-Korean Senior (NHIS-Korean Senior) claim
      database, consisting of a random sample of 10% of adults aged 60 years and older.
      At baseline in 2002 121,733 subjects, who were admitted to the hospital at least
      once a year between 2002 and 2008, were analyzed. We used the Cox proportional
      hazards models after growth mixture modeling (GMM) to estimate trajectories in
      the combined comorbidity Index scores which is the Gagne's method between 2002
      and 2008, and their 1-, 3-, and 5-year mortality rates. Five comorbidity
      trajectory groups were generated: consistently low, increased, decreased/low,
      decreased/high, and consistently high. After adjusting for all confounders,
      compared with decreased/low, the consistently high group presented the highest
      mortality risk (p < 0.001; Ptrend < 0.001), with hazard ratios (HR) of 3.48 at 1
      year, 2.53 at 3-year, and 1.92 at 5-year follow-up, followed by the increased and
      decreased/high groups. Five distinct comorbidity trajectories were identified
      that predicted increased risk of mortality. The group with the consistently high
      comorbidity scores over time exhibited the highest mortality risk.

PMID- 30118925
TI  - An examination of emotional and loss-of-control eating after sleeve gastrectomy
      surgery.
AB  - Emotional eating has been identified as a predictor of poorer weight loss
      outcomes in non-bariatric clinical samples. It is unknown, however, whether
      emotional eating contributes to poorer weight loss outcomes after bariatric
      surgery or how it might be associated with loss-of-control (LOC) eating, a known
      predictor of post-surgical outcomes. This study examined the nature and
      significance of emotional eating among post-bariatric surgery patients with LOC
      eating. Participants (N = 134) were patients with LOC eating (at least once
      weekly) seeking treatment to help improve eating approximately 4-9 months
      following sleeve gastrectomy surgery. Participants were assessed with the Eating
      Disorder Examination-Bariatric Surgery Version interview, Yale Emotional
      Overeating Questionnaire, and Beck Depression Inventory-II. Emotional eating and
      LOC eating were significantly negatively correlated with post-surgical weight
      loss (p's < 0.05), both variables had a small effect. Linear regression analyses
      revealed that both emotional eating and frequency of LOC eating were
      independently associated with weight loss (R2 = 0.041 and 0.049, respectively).
      Our findings suggest that, among post-sleeve gastrectomy patients with LOC
      eating, greater frequency of LOC eating and LOC eating in response to emotions
      are associated with poorer weight outcomes.

PMID- 30118927
TI  - Loss of thin spines and small synapses contributes to defective hippocampal
      function in aged mice.
AB  - Aging is a normal physiological process associated with impairments in cognitive
      function, including learning and memory. Here, the underlying synaptic mechanisms
      by which aging leads to the decline of spatial learning and memory function were
      investigated in 25-month-old aged mice versus 2-month-old young mice. Deficits of
      spatial learning and memory, as well as selective loss of thin spines, but not
      mushroom-type spines on apical dendrites of CA1 pyramidal cells were found in
      aged mice. Specifically, loss of thin spines in aged mice with memory deficits
      was primarily found on dendritic segments located in the Schaffer pathway, and
      the density of thin spines significantly correlated with spatial memory
      performance. The loss of thin spines was evidenced by a decrease in small
      synapses that express diminutive amounts of postsynaptic density protein-95 and
      alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit GluR1.
      Furthermore, mushroom-type spines and GluR1-expressed large synapses were not
      affected in aged mice with impaired memory. Taken together, these data suggest
      that the selective loss of those highly plastic thin spines with sparse
      postsynaptic density protein-95 and GluR1 receptors may significantly contribute
      to cognitive deficits in aged individuals.

PMID- 30118926
TI  - Mycobacterium vaccae immunization protects aged rats from surgery-elicited
      neuroinflammation and cognitive dysfunction.
AB  - Aging is a major risk factor for developing postoperative cognitive dysfunction.
      Neuroinflammatory processes, which can play a causal role in the etiology of
      postoperative cognitive dysfunction, are potentiated or primed as a function of
      aging. Here we explored whether exposure to a microorganism with immunoregulatory
      and anti-inflammatory properties, Mycobacterium vaccae NCTC 11659 (M. vaccae),
      could ameliorate age-associated neuroinflammatory priming. Aged (24 months) and
      adult (3 months) male F344XBN rats were immunized with heat-killed M. vaccae (3
      injections, once per week) before undergoing a laparotomy or anesthesia control
      procedure. Aged, but not young rats, showed postoperative learning/memory
      deficits in a fear-conditioning paradigm. Importantly, M. vaccae immunization
      protected aged rats from these surgery-induced cognitive impairments. M. vaccae
      immunization also shifted the aged proinflammatory hippocampal microenvironment
      toward an anti-inflammatory phenotype. Furthermore, M. vaccae immunization
      reduced age-related hyperinflammatory responses in isolated hippocampal
      microglia. Overall, our novel data suggest that M. vaccae can induce an anti
      inflammatory milieu in the aged brain and thus mitigate the neuroinflammatory and
      cognitive impairments induced by surgery.

PMID- 30118929
TI  - Ictal nausea and vomiting - Is it left or right?
AB  - PURPOSE: Ictal nausea/vomiting has been linked to the non-dominant hemisphere and
      has been considered a lateralizing sign. However, small case series and single
      cases have reported seizure localisation in the dominant hemisphere. Here we
      aimed to determine the seizure localisation and lateralization in cases with
      ictal nausea/retching/vomiting to test the hypothesis that these signs are of
      lateralizing value. METHODS: We searched two large tertiary epilepsy-center video
      EEG databases (period: 1980-2017) for reports on ictal nausea/retching/vomiting
      and retrieved ictal EEG seizure location, lateralization and clinical symptoms.
      RESULTS: We identified 13 patients with focal epilepsy and video-EEG-documented
      ictal nausea (n = 2), nausea and retching (n = 3), retching followed by vomiting
      (n = 5) or only vomiting (n = 3). Aetiology was genetic (n = 1),
      structural/metabolic (n = 7) or of unclear origin (n = 5). While in 12/13
      patients epileptic discharges were temporal, a single case was parietal. A left
      sided seizure origin was more frequent than a right-sided origin (62 vs. 38%).
      Assuming a left-sided language dominance in the single left-handed patient and in
      those two patients with unclear handedness (based on the known distribution of
      hemispheric speech-dominance), the distribution of ictal nausea/retching/vomiting
      to the dominant vs. non-dominant hemisphere was not significantly different from
      a random distribution (8 vs. 5, p = 0.581). CONCLUSION: Ictal
      nausea/retching/vomiting are most frequently of temporal origin. In contrast to
      previous studies, our ictal video-EEG data suggests that these signs have no
      lateralizing value. Thus, video-EEG should be performed and while this clinical
      sign points to a temporal seizure origin, it does not determine its
      lateralization.

PMID- 30118928
TI  - Long-term retention rates of antiepileptic drugs used in acute seizures.
AB  - PURPOSE: A number of antiepileptic drugs (AEDs) are currently available for
      treating acute seizures. It is recommended to select the initial treatment option
      according to the type of epileptic syndrome and the patient's clinical
      characteristics, but little is known about the long-term retention rates of AEDs
      started in the emergency department. METHODS: We recruited patients admitted with
      seizures over a two-year period. All patients underwent early neurological
      assessment, EEG testing, and neuroimaging. The treatments received at baseline
      and at one year of follow-up were compared. RESULTS: In total, 225 patients were
      included. Overall, monotherapy with levetiracetam was the regimen most often used
      in patients with new-onset seizures, whereas other AEDs were mainly used in
      patients previously treated with other drugs. Lacosamide use was most likely
      associated with the presence of lesion related seizures in elderly patients, and
      carboxamides with focal onset seizures of unknown cause. The mean retention rate
      of the total of AED treatments was nearly 70%. The main cause leading to
      discontinuation was the development of intolerable adverse events. Levetiracetam
      use decreased as lacosamide use increased in the overall group of patients.
      CONCLUSION: Our study shows that there is a trend to use newer AEDs, particularly
      levetiracetam, as the first option in new-onset seizures in the emergency room.
      However, levetiracetam use significantly decreased over follow-up, mainly because
      of the development of adverse events. The use of other, better-tolerated AEDs,
      such lacosamide predominated in elderly patients and patients with lesion related
      seizures, or carboxamides in epilepsies of unknown etiology.

PMID- 30118930
TI  - Presurgical hyperconnectivity of the ablation volume is associated with seizure
      freedom after magnetic resonance-guided laser interstitial thermal therapy.
AB  - PURPOSE: Magnetic Resonance-guided Laser Interstitial Thermal Therapy (MRgLITT)
      is an emerging minimally-invasive alternative to resective surgery for medically
      intractable epilepsy. The precise lesioning effect produced by MRgLITT supplies
      opportunities to glean insights into epileptogenic regions and their interactions
      with functional brain networks. In this exploratory analysis, we sought to
      characterize associations between MRgLITT ablation zones and large-scale brain
      networks that portended seizure outcome using resting-state fMRI. METHODS:
      Presurgical fMRI and intraoperatively volumetric structural imaging were
      obtained, from which the ablation volume was segmented. The network properties of
      the ablation volume within the brain's large-scale brain networks were
      characterized using graph theory and compared between children who were and were
      not rendered seizure-free. RESULTS: Of the seventeen included children, five
      achieved seizure freedom following MRgLITT. Greater functional connectivity of
      the ablation volume to canonical resting-state networks was associated with
      seizure-freedom (p < 0.05, FDR-corrected). The ablated volume in children who
      subsequently became seizure-free following MRgLITT had significantly greater
      strength, and eigenvector centrality within the large-scale brain network.
      CONCLUSIONS: These findings provide novel insights into the interaction between
      epileptogenic cortex and large-scale brain networks. The association between
      ablation volume and resting-state networks may supply novel avenues for
      presurgical planning and patient stratification.

PMID- 30118931
TI  - Does emergent implantation of a vagal nerve stimulator stop refractory status
      epilepticus in children?
AB  - PURPOSE: Status Epilepticus can be a serious life threatening event in epileptic
      patients. The definition of refractory or super-refractory Status Epilepticus was
      based on the therapeutic response to anti-epileptic and anesthetic drugs. Vagal
      Nerve Stimulation showed efficacy in treating drug-resistant epilepsy but there
      are only few reports on emergentplacement of Vagal Nerve Stimulator for
      refractory or super-refractory Status Epilepticus. METHODS: Among 49 children
      implanted at our Institution with Vagal Nerve Stimulation for drug-resistant
      epilepsy, the authors retrospectively identified those implanted for refractory
      or super-refractory Status Epilepticus, according with the current definitions.
      RESULTS: 4 patients were operated upon at ages ranging 7 to 17 months and reached
      the programmed output current of 1 mA over a time ranging from 24 to 36 h (fast
      ramping-up). In 3 out of 4 patient we observed the abrupt of Status Epilepticus;
      one patient was refractory both to drugs and Vagal Nerve Stimulation and later
      died, without recovering from SE. At follow up, ranging from 24 to 45 months, the
      remaining 3 patients showed a decrease of the seizures frequency >80% without
      relapse of Status Epilepticus; in all the patients, output current and/or Duty
      Cycle were increased later. CONCLUSION: VNS can be effective in treating
      refractory or super-refractory Status Epilepticus.

PMID- 30118932
TI  - Tolerability, efficacy and retention rate of Brivaracetam in patients previously
      treated with Levetiracetam: A monocenter retrospective outcome analysis.
AB  - PURPOSE: To determine the potential for improvement of tolerability and efficacy
      by the use of Brivaracetam (BRV) in patients previously treated with
      Levetiracetam (LEV). METHODS: We retrospectively analyzed data from patients
      treated with BRV at the Freiburg Epilepsy Center. RESULTS: 102 patients with a
      minimum follow up of 6 months were included. The mean duration of treatment was
      301.6 (+/- 156.8) days. 60 patients underwent an overnight switch from LEV to
      BRV, 42 patients have had LEV at some time in the past. Out of 46 patients with a
      quantifiable seizure baseline and follow-up of 6 months 10 patients (21.7%) had
      an increase in seizure frequency, 15 (32.6%) were 50%-responders, and 10 patients
      (21.7%) became newly seizure-free. Patients with an overnight switch from LEV to
      BRV who had a reduction in seizure frequency had the highest dose ratio of the
      final BRV dose to LEV (1:10.1) and the biggest difference between the starting
      and final dose of BRV, suggesting that previously seizure control was limited by
      the tolerated LEV dosage. The retention rate after 6 months was 80.4%. 28 out of
      49 (57.1%) patients directly switched from LEV to BRV because of psychiatric side
      effects reported an improved tolerability. 10 out of 42 (23.8%) patients not
      directly switched but with a history of LEV use had predominantly psychiatric
      side effects during BRV treatment. CONCLUSION: Overall, intolerability or
      ineffectiveness of prior treatment with LEV seems not to preclude a good response
      to BRV. BRV was substantially better tolerated than LEV.

PMID- 30118933
TI  - Foam dressings for treating pressure injuries in patients of any age in any care
      setting: An abridged Cochrane systematic review.
AB  - BACKGROUND: Pressure injuries are localised areas of injury to the skin and/or
      underlying tissues. OBJECTIVES: To assess foam dressings compared to other
      dressings in healing pressure injuries. DESIGN: Systematic review and meta
      analysis DATA SOURCES: The review team searched: the Cochrane Wounds Specialised
      Register; the Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Ovid
      Embase; EBSCO CINAHL Plus and the NHS Economic Evaluation Database. Authors also
      searched clinical trials registries and scanned reference lists for reviews, meta
      analyses and health technology reports. No restrictions were applied to language,
      publication date or study setting. STUDY ELIGIBILITY CRITERIA: Published or
      unpublished randomised controlled trials and cluster- randomised controlled
      trials that examined the clinical or cost effectiveness of foam dressings for
      healing pressure injuries. PARTICIPANTS: Patients of any age with a pressure
      injury of Stage II or above in any care setting. INTERVENTIONS: Use of any foam
      wound dressing for treating Stage II pressure injuries or above. STUDY APPRAISAL
      AND SYNTHESIS METHODS: Full-text were assessed for eligibility using a priori
      criteria by two authors. Risk of bias was assessed using the Grading of
      Recommendations, Assessment, Development and Evaluation criteria, and
      Consolidated Health Economic Evaluation Reporting Standards. Risk ratio and mean
      difference with 95% confidence intervals were used to measure the effect. The
      review team used Review Manager 5 to enter narrative and qualitative data of
      included studies. RESULTS: Authors found nine studies published between 1994 and
      2016 involving 483 participants with pressure injuries at Stage II or above.
      Included studies compared foam dressings with other types of dressings. However,
      it was unclear if the foam dressing affected healing (RR 1.00, 95% CI 0.78-1.28),
      time to complete healing (MD 5.67 days 95% CI-4.03-15.37), adverse events (RR
      0.33, 95% CI 0.01-7.65), or reduction in pressure injury size (MD 0.30 cm2 per
      day, 95% CI -0.15 to 0.75), as the certainty of the evidence was very low.
      LIMITATIONS: Using the Grading of Recommendations, Assessment, Development and
      Evaluation criteria, the certainty and completeness of evidence was low to very
      low, making it difficult to draw comparisons between foam and other dressings.
      CONCLUSIONS AND IMPLICATIONS: It is uncertain whether foam dressings are more
      clinically effective, more acceptable to users, or more cost effective compared
      to alternative dressings in treating pressure injuries.

PMID- 30118934
TI  - Effects of ferric sulfate and polyaluminum chloride coagulation enhanced
      treatment wetlands on Typha growth, soil and water chemistry.
AB  - Land surface subsidence is a concern in many deltas worldwide as it contributes
      to water quality degradation, loss of fertile land and increased potential for
      levee failure. As a possible solution to these concerns, on-site coagulation
      enhanced treatment wetlands (CETWs), coagulation water treatment followed by
      wetland passage serving as a settling basin, were implemented in a field-scale
      study located on a subsided island of the Sacramento-San Joaquin Delta in
      northern California under three treatments; coagulation with polyaluminum
      chloride (PAC), coagulation with ferric sulfate and an untreated control. Because
      CETWs offer a relatively novel solution for water quality improvement and
      subsidence reversal due to its low-infrastructure requirements and in-situ
      nature, effects from these systems remain uncharted and they may have adverse
      effects on plant biomass production that also contribute to sediment accretion.
      This study focuses on the effect CETWs had on the growth of Typha spp.; the
      dominant vegetation in the wetlands. Plant growth parameters and nutrient content
      were measured in conjunction with soil, pore water and surface water chemistry.
      Soil analysis indicated there was no intermixing of newly formed flocs and
      original soil material. Where there was significant deposition of floc, PAC
      treatment reduced phosphate concentrations and ferric sulfate treatment increased
      total Fe concentrations in surrounding water compared to the control. Results
      indicated coagulation treatments had no negative effects on Typha leaf nutrient
      content, Typha growth or allometric parameters. Additionally, no signs of plant
      toxicity such as necrosis, wilting or chlorosis were observed in any of the
      treatments. Overall, this study suggests that CETWs are viable treatment option
      for water quality improvement and sediment accretion while having no negative
      impact on the growth of Typha plants.

PMID- 30118935
TI  - Multiple assessments of trace metals in sediments and their response to the water
      level fluctuation in the Three Gorges Reservoir, China.
AB  - Response of trace metals to the consecutive water level fluctuation in the Three
      Gorges Reservoir (TGR) sediments remains unclear. Here, we evaluated the
      influence of consecutive stages of water level fluctuation on trace metal
      pollution using multiple analytical approaches. The spatio-temporal distributions
      of trace metals in TGR sediments were investigated for five consecutive water
      impoundment stages from 2015 to 2017. Anthropogenic contributions and trace metal
      stocks in the TGR were quantitatively estimated using a combination of a regional
      geochemical baseline (RGB) and annual sediment load. Results showed that trace
      metals were accumulated after the construction and impoundment of the TGR.
      However, after the TGR operated normally for more than five years, trace metals
      concentrations stabilized in sediments. Trace metal concentrations in the
      mainstream were slightly higher than those in the tributaries. In the mainstream,
      metal concentrations in the upstream were lower than those in the midstream and
      downstream except for Cd. Anthropogenic contributions of trace metals ranged from
      8.51 to 24.86% and were highest for Hg and Cd. The sediment load was the main
      factor influencing trace metal stock in TGR sediments. Although the total Cd
      stock amount was relatively low, its potential ecological effects are of great
      concern due to its high mobile fraction percentages and toxicity. The RGB-based
      geo-accumulation index and potential ecological risk index showed that TGR
      sediments were uncontaminated, and were subject to low ecological risk from trace
      metals. This result differs from traditional assessment results, indicating that
      previous assessments may overestimate the ecological risks of the trace metals in
      the TGR. The health risks posed by trace metals bio-accumulated in fish, stemming
      from sediment resuspension, were assessed using an environmental impact
      assessment model. Results suggested that residents should not experience
      significant health risks from the intake of individual metals through fish
      consumption.

PMID- 30118936
TI  - Research on the sustainable efficacy of g-MoS2 decorated biochar nanocomposites
      for removing tetracycline hydrochloride from antibiotic-polluted aqueous
      solution.
AB  - Antibiotic concentrations in surface waters far exceed the pollution limit due to
      the abuse of pharmaceuticals, resulting in an urgent need for an approach with
      potential efficiency, sustainability and eco-friendliness to remove antibiotic
      pollutants. A novel biochar-based nanomaterial was synthesized by hydrothermal
      synthesis and was investigated for its removal potential for tetracycline
      hydrochloride (TC) from both artificial and real wastewater. The associative
      facilitation between biochar and g-MoS2 nanosheets was proposed, revealing the
      favorable surface structures and adsorption properties of the composite. The
      related adsorption kinetics, isotherms and thermodynamics were studied by several
      models with adsorption experimental data, turning out that biochar decorated by g
      MoS2 exhibited optimum TC removal with adsorption capacity up to 249.45 mg/g at
      298 K. The adsorption behavior of TC molecules on g-MoS2-BC can be interpreted
      well by three-step process, and it is dominated by several mechanisms containing
      pore-filling, electrostatic force, hydrogen bond and pi-pi interaction. In
      addition, the cost-effective g-MoS2-BC nanocomposites demonstrated excellent
      adsorption and recycling performance in TC-contaminated river water, which might
      provide the underlying insights needed to guide the design of promising approach
      for contaminant removal on a large scale in practical application.

PMID- 30118937
TI  - Modelling strontium isotopes in past biospheres - Assessment of bioavailable
      87Sr/86Sr ratios in local archaeological vertebrates based on environmental
      signatures.
AB  - 87Sr/86Sr isotopic ratios in skeletal remains of archaeological vertebrates are
      used for provenance analysis since long. However, the definition of the past
      bioavailable isotopic ratio at the site of recovery is not known beforehand and
      geological maps can provide no more than gross expectations. Therefore, the
      assessment of the "local Sr isotopic signature" is still of crucial importance.
      In this study, we present a tool for the prediction of such local isotopic
      signatures by creating a concentration weighted mixing model that links
      lithospheric, biospheric, and atmospheric strontium per site. The major strontium
      sources and their input into an animal's body were assessed by choosing elemental
      strontium and its isotopic signature in groundwater, soil, vegetation, and
      precipitation as components for the mixing model, augmented by literature values.
      The model was applied to 24 sites located in the alpine transect of the Inn
      Eisack-Adige-Brenner passage across the European Alps, a passage used since the
      Mesolithic. Predicted local bioavailable 87Sr/86Sr ratios were compared with
      measured values from locally excavated archaeozoological bone samples from three
      taxa of large and mainly residential vertebrates (cattle, pig, red deer) to
      verify the models' accuracy. With regard to the fact that the environmental
      samples predict the past local bioavailable 87Sr/86Sr at a specific site while
      the vertebrates had different and species-specific home ranges, thereby
      integrating strontium from a region of primarily unknown size, the model is
      capable of assigning reasonable expectation values. For 11 sites, up to 100% of
      the vertebrate isotopic signatures were correctly predicted. Mismatches at the
      remaining sites are explainable by special environmental factors, and also the
      fact that some import of animals can never be excluded beforehand. Suggestions
      for site-specific adjustments of the model are made.

PMID- 30118938
TI  - Variations and sources of nitrous acid (HONO) during a severe pollution episode
      in Beijing in winter 2016.
AB  - HONO is an important precursor of OH radical and plays a key role in atmospheric
      chemistry, but its source and formation mechanism remain uncertain, especially
      during complex atmospheric pollution processes. In this study, HONO mixing ratios
      were measured by a custom-made instrument during a severe pollution event from 16
      to 23 December 2016, at an urban area of Beijing. The measurement was divided
      into three periods: I (haze), II (severe haze) and III (clean), according to the
      levels of PM2.5. This pollution episode was characterized by high levels of NO
      (75 +/- 39 and 94 +/- 40 ppbV during periods I and II, respectively) and HONO (up
      to 10.7 ppbV). During the nighttime, the average heterogeneous conversion
      frequency during the two haze periods were estimated to be 0.0058 and 0.0146 h-1,
      and it was not the important way to form HONO. Vehicle emissions contributed 52%
      (+/-16)% and 40% (+/-18)% to ambient HONO at nighttime during periods I and II.
      The contribution of homogeneous reaction of NO with OH should be reconsidered
      under high-NOx conditions and could be noticeable to HONO sources during this
      pollution event. Furthermore, HONO was positively correlated with PM2.5 during
      periods I and II, suggesting a potential chemical link between HONO and haze
      particles.

PMID- 30118939
TI  - Optimization of a single chamber microbial fuel cell using Lactobacillus
      pentosus: Influence of design and operating parameters.
AB  - Microbial fuel cells (MFCs) have been receiving an increased attention over the
      last years due to their potential to combat two global problems: waste pollution
      and energy demand. Additionally, when a wastewater is used, MFCs can perform its
      treatment while recovering energy, leading to the possibility of energy-producing
      wastewater treatment plants, offsetting their operational costs. However, to
      overcome their current limitations (lower power outputs and higher costs), a
      clear understanding of the effect of operation and design parameters on its
      overall performance is mandatory. Therefore, the goal of this work was to
      evaluate the effect of operating conditions - batch cycle and yeast extract
      concentration, and design parameters - anode electrode area, membrane thickness
      and active area, on the overall performance of a single chamber MFC. The MFC
      operated with a pure culture of Lactobacillus pentosus and a synthetic wastewater
      based on a real dairy industry effluent. The overall performance was evaluated
      through the power output and the COD removal rate. Additionally, the biofilm
      formed at the anode electrode was characterized in terms of biomass, proteins and
      polysaccharides content. For the conditions used in this work, a maximum power
      density of 5.04 +/- 0.39 mW/m2 was achieved with an anode electrode area of 61
      cm2, a batch cycle of 48 h, 50 mg/L of yeast extract and a Nafion 212 membrane
      with an active area of 25 cm2. The different conditions tested had a clear effect
      on the MFC energy production and biofilm characteristics, but not on the ability
      of L. pentosus to treat the dairy wastewater. The COD removal rates were in the
      range between 42% and 58%, for all the conditions tested.

PMID- 30118940
TI  - Inactivation of two Mycobacteria by free chlorine: Effectiveness, influencing
      factors, and mechanisms.
AB  - Chlorination is one of the most widely used disinfection techniques, and the
      problem of "chlorine-resistant bacteria" (CRB) has attracted more attention
      recently. In this study, the deactivation of typical CRB in water, Mycobacterium
      fortuitum (M. fortuitum) and Mycobacterium mucogenicum (M. mucogenicum), by free
      chlorine was investigated with Escherichia coli (E. coli) and Bacillus subtilis
      (B. subtilis) as the reference. The chlorination effectiveness of chlorine on M.
      fortuitum and M. mucogenicum and the effect of chlorine concentration, pH, and
      humic acid were studied. It was found that M. mucogenicum was more resistant to
      chlorine than M. fortuitum, both of which were much more resistant than E. coli
      and B. subtilis. The effect of disinfectant concentration on the inactivation
      efficiency was positive, whereas the influence of pH and humic acid was negative.
      The inactivation mechanisms were explored by analyzing the bacteria morphology,
      the destruction of cell membrane, the cell hydrophobicity, as well as total
      adenosine triphosphate (ATP), superoxide dismutase (SOD) activity. The slight
      destruction of the cell membrane was observed after deactivation with chlorine,
      and high hydrophobicity of the cell membrane combined with metabolic changes
      might lead to the chlorine tolerance of Mycobacteria.

PMID- 30118941
TI  - Evaluating the use of fire to control shrub encroachment in global drylands: A
      synthesis based on ecosystem service perspective.
AB  - With the proliferation of woody plant species in much of the world's grasslands,
      human has manipulated landscape fire to return their forage provisioning service.
      Yet other ecosystem services (e.g., carbon sequestration, biodiversity
      conservation, erosion control) in the post-managed areas compared to those
      previously available in the shrub-encroached area are largely unknown, including
      trade-offs between ecosystem services. Using data from previous publications, we
      quantitatively synthesized the sustainability of fire as shrub management
      practice, expressed as its efficacy to control shrubs and its capacity to
      maintain different ecosystem services. A simple indicator (delta), defined as the
      ratio of an observed ecological attribute between area experiencing shrub
      management and untreated control, was used to quantify the changes. Our results
      showed that fire could be an effective strategy to control shrubs and to increase
      forage provisioning service (deltaherbaceous biomass = 1.39). However, there are
      possible trade-offs with other ecosystem services (e.g., erosion control,
      nutrient cycling) when a 54% increase in bare soil cover (deltabare soil = 1.54)
      and ~74% loss of biological soil crusts cover (deltabiological crust = 0.26) were
      found. Because increasing forage provisioning at the cost of other ecosystem
      services might not be sustainable, management should focus on strategies to
      minimize such trade-offs, which may include but not limited to rotational
      grazing, adjustment in stocking rate, or supplementary external inputs (e.g.,
      fertilizer). Unless those measures are employed, there is possible emergence of a
      novel crash (i.e., vegetation- and resource-poor scabland) resulting from a
      combination of soil erosion and high vulnerability of burnt landscape to exotic
      species invasion.

PMID- 30118942
TI  - First granted example of novel FDA trial design under Expedited Access Pathway
      for premarket approval: BeAT-HF.
AB  - BACKGROUND: The Food and Drug Administration (FDA) initiated the Expedited Access
      Pathway (EAP) to accelerate approval of novel therapies targeting unmet needs for
      life-threatening conditions. EAP allows for the possibility of initial FDA
      approval using intermediate end points with postapproval demonstration of
      improved outcomes. OBJECTIVE: Describe the EAP process using the BeAT-HF trial as
      a case study. METHODS: BeAT-HF will examine the safety and effectiveness of
      baroreflex activation therapy (BAT) in heart failure patients with reduced
      ejection fraction using an Expedited and Extended Phase design. In the Expedited
      Phase, BAT plus guideline-directed medical therapy (GDMT) will be compared at 6
      months postimplant to GDMT alone using 3 intermediate end points: 6-minute hall
      walk distance, Minnesota Living with Heart Failure Questionnaire, and N-terminal
      pro-B-type natriuretic peptide. The rate of heart failure morbidity and
      cardiovascular mortality will be compared between the arms to evaluate early
      trending using predictive probability modeling. Sample size of 264 patients
      randomized 1:1 to BAT + GDMT versus GDMT alone provides 81% power for the
      Expedited Phase intermediate end points. For the Extended Phase, the heart
      failure morbidity and cardiovascular mortality end point is based on an expected
      event rate of 0.4 events/patient/year in the GDMT arm. With an adaptive sample
      size selection design for robustness to inaccurate assumptions, a sample size of
      480-960 randomized patients followed >=2 years allows detecting a 30% reduction
      in the primary end point with a power of 97.5%. CONCLUSION: Through a unique
      collaboration with FDA under the EAP, the BeAT-HF trial design allows for the
      possibility of approval of BAT, initially for symptom relief and subsequently for
      outcomes improvement.

PMID- 30118943
TI  - Cognitive reappraisal moderates the relationship between PTSD symptoms and
      alcohol use over time in post-9/11 U.S. military veterans.
AB  - BACKGROUND: Rates of comorbid alcohol use disorder (AUD) and posttraumatic stress
      disorder (PTSD) are increasing among post-9/11 veterans, and emotion regulation
      problems have been identified as a feature of both disorders. However, no studies
      to date have explored how individual differences in emotion regulation may
      moderate the relationship between PTSD symptoms and alcohol use. We evaluated how
      two core emotion regulation strategies - one adaptive (i.e., cognitive
      reappraisal) and one maladaptive (i.e., expressive suppression) are related to
      PTSD symptoms and alcohol use over one-year. METHODS: A total of 71 post-9/11
      veterans (12 female, 59 male) completed a baseline screening and at least two
      follow-up assessments over the course of 12 months which included measures of
      emotion regulation, PTSD symptoms, and alcohol use. A mixed growth model was
      utilized to determine if changes in PTSD symptoms covaried with alcohol use over
      time and whether this relation was moderated by frequency of use of emotion
      regulation strategies. RESULTS: In general, higher PTSD symptoms were
      significantly associated with greater alcohol use, but cognitive reappraisal
      moderated this relationship. Specifically, at low cognitive reappraisal, greater
      PTSD symptoms were associated with greater alcohol use. At high cognitive
      reappraisal, there was no significant association between PTSD symptoms and
      alcohol use. CONCLUSIONS: Findings from the present study suggest that baseline
      individual differences in cognitive reappraisal influence the relation between
      PTSD symptoms and alcohol use. For post-9/11 veterans, high levels of cognitive
      reappraisal may serve as a protective factor against ongoing alcohol use.

PMID- 30118944
TI  - Changes in the levels of depressive symptoms and anxiety in Ansan city after the
      2014 Sewol ferry disaster.
AB  - BACKGROUND: In April 2014, a ferry carrying 476 passengers sunk on the coast of
      Korea, resulting in 304 deaths. Of these, 250 were local high school students,
      and the disaster significantly affected their community. This study aimed to
      examine the prevalence of depressive symptoms and anxiety among Ansan city
      residents to understand their recovery process after the accident. METHODS: Two
      cross-sectional surveys (survey 1, after 4-6 months and survey 2, after 16-18
      months of disaster) were used to compare prevalence among residents of Ansan city
      and adjacent cities. Symptoms were determined by the Center for Epidemiologic
      Studies-Depression Scale and the Generalized Anxiety Disorder 7-item Scale.
      RESULTS: A total of 1,773 and 1,748 participants were included in Survey 1 and
      Survey 2, respectively. Survey 1 showed a significantly higher prevalence of
      depressive symptoms (19.0%; 95% confidence interval [CI], 16.9-21.1) and anxiety
      (6.1%; 95% CI, 5.0-7.5) among Ansan city, compared to participants from adjacent
      cities (depressive symptoms: 14.3%; 95% CI, 12.7-16.1; anxiety: 3.6%; 95% CI, 2.9
      4.5). Survey 2 showed a decreased prevalence of depression (15.8%; 95% CI, 14.0
      17.9) and anxiety (5.0%; 95% CI, 4.0-6.4) among Ansan city residents. Depressive
      symptoms and anxiety adjusted odds ratio in survey 2 compared with survey 1 were
      0.74 (95% CI 0.62-0.89) and 0.81 (0.60-1.08) among Ansan city, respectively.
      LIMITATIONS: Cross-sectional study design and lack of pre-disaster baseline data
      for comparison are limitations of this study. CONCLUSIONS: Psychological distress
      occurred at a population level, not only among survivors and their families, but
      also among Ansan city residents indirectly impacted by the traumatic event.
      Although populations indirectly affected by a disaster show a natural recovery
      process, timely population-based interventions may be helpful.

PMID- 30118945
TI  - Prenatal maternal anxiety and children's brain structure and function: A
      systematic review of neuroimaging studies.
AB  - BACKGROUND: Maternal anxiety disorders are common during pregnancy and
      postpartum, and are associated with increased behaviour problems and risk of
      mental health difficulties in children. Understanding alterations in brain
      structure and function associated with maternal anxiety may help elucidate
      potential mechanisms via which high maternal anxiety could affect children.
      METHODS: We conducted a systematic review of extant research studying the
      associations between prenatal anxiety and children's brain structure and
      function, as assessed through neuroimaging. Data were gathered in accordance with
      the PRISMA review guidelines. RESULTS: Ten articles were identified, and all
      found a significant association between antenatal maternal anxiety and child
      neurodevelopment. Studies vary considerably in their methods with five studies
      employing electroencephalography (EEG), one using magnetoencephalography (MEG),
      and the rest employing magnetic resonance imaging (MRI). LIMITATIONS: The
      heterogeneity of neuroimaging techniques undertaken by the reviewed studies
      precluded a meta-analysis from being performed. The applicability of this
      systematic review to clinical practice is also limited given that the studies
      examined children across a wide age range (neonates to 17 years). CONCLUSIONS:
      From early infancy to late adolescence, findings suggest alterations of brain
      structure and function in frontal, temporal, and limbic areas in children born to
      mothers who experienced prenatal anxiety. These brain abnormalities may underlie
      associations between prenatal anxiety and children's behaviour, though more
      research incorporating neuroimaging and behavioural data is necessary to
      determine this.

PMID- 30118946
TI  - The Darknet and suicide.
AB  - CONTEXT: The Internet contains both public content ("Surface Web"), and private
      content ("Deep Web") sometimes hosted on exclusive networks ("Darknets") only
      accessible using dedicated software such as TOR (The Onion Router). This software
      makes it almost impossible to identify its users. Information media have reported
      on suicide-related aspects of Darknets, for example when poisons that can be used
      to kill oneself are offered for sale (Le Garff et al., 2016) when users discuss
      ways to kill oneself in anonymous forums (Ferrara, 2016; Franceschi-Bicchierai,
      2015) and suicides that follow bullying or "doxing" (online divulgation without
      consent of intimate personal information) (Bartlett, 2015). Several recent
      studies have analyzed the nature of suicide content on the Surface Web, but to
      date, there have been no systematic investigations of suicidal content available
      on Darknets. OBJECTIVES: The object was to document the nature and accessibility
      of suicide-related information available on the TOR Darknet or via the TOR
      software. METHODS: We replicated the methodology used by Biddle et al. (2008,
      2016) in their studies of the Surface Web, using TOR on the Darknet. We
      identified and chose nine search engines used on the TOR Darknet: TORCH the TOR
      search engine, Notevil, Ahmia, Candle, Hidden Wiki, Darknet (onion.link),
      Duckduckgo and Grams. Two research assistants independently coded the first 30
      results of searches using the keywords, "suicide" and "suicide methods". RESULTS:
      There were 476 "hits" in the search for "suicide" and "suicide method" using TOR,
      with fewer sites dedicated to suicide (4%), compared to the Surface Web (23.1%)
      (Biddle et al., 2016). Over half of the sites proposed by the TOR search engines
      (252, 52.9%) were outdated, inaccessible or not containing content pertinent to
      suicide or suicide methods. Several of the TOR search engines provided access to
      forums ("chat boards") where suicide was a topic (70, 14.8%). These were usually
      pro-suicide, are blocked or filtered by most of the Surface Web engines (e.g.
      Google). DISCUSSION: Persons concerned with suicide prevention should conduct
      further investigations of pro-suicide forums that are accessible using TOR and
      their users, comparing them with the Surface Web. New strategies to prevent
      suicide may need to be developed for Darknets.

PMID- 30118947
TI  - Identification and expression of transcription factor sox2 in large yellow
      croaker Larimichthys crocea.
AB  - As an important transcription and pluripotency factor, Sox2 plays its functions
      essentially in the regulation of self-renewal and pluripotency of embryonic and
      neural stem cells, as well as embryogenesis, organogenesis, neurogenesis and
      regeneration. The data is lacking on Sox2 in large yellow croaker (Larimichthys
      crocea) (Lc-Sox2) which is a limitation on the generation of induced pluripotent
      stem cells (iPSCs). In this study, Lc-sox2 was cloned by RACE (rapid
      amplification of cDNA ends) and analyzed by Bioinformatics. The quantitative real
      time PCR (qRT-PCR) and whole mount in situ hybridization (WISH) were used to
      detect the expression of Lc-sox2. The full-length cDNA sequence of Lc-sox2 is
      2135 bp and encodes a 322-aa (amino acids). Lc-Sox2 possesses a highly conserved
      HMG-box as DNA-binding domain, maintains highly conserved with vertebrates,
      particularly with teleosts. In tissues, Lc-sox2 was expressed with gender
      difference in brain and eye (female > male), in embryos, Lc-sox2 was expressed
      with a zygotic type that the high level expression began to appear in the
      gastrula stage. The spatio-temporal expression patterns of Lc-sox2 suggested the
      potential involvement in embryogenesis, neurogenesis, gametogenesis and adult
      physiological processes of large yellow croaker. Our results contributed to
      better understanding of Sox2 from large yellow croaker.

PMID- 30118948
TI  - Linear relationship between cytoplasm resistance and hemoglobin in red blood cell
      hemolysis by electrical impedance spectroscopy & eight-parameter equivalent
      circuit.
AB  - We have developed a non-invasive rapid and real-time red blood cell (RBC)
      hemolysis detection method which is a more accurate for point of care testing of
      hemolysis in various medical settings. An eight-parameter equivalent circuit is
      employed to quantify the release of hemoglobin (Hb) and the cytoplasm from RBC
      into the blood plasma. RBC hemolysis is induced by adding different volume
      fractions of distilled water into the blood. The cytoplasm released following RBC
      hemolysis is estimated from the experimental values. A strong relationship
      between RBC hemolysis and change in the electrical characteristics of blood has
      been demonstrated. The cytoplasm resistance (Rc) shows a linear relationship with
      the Hb. This relationship between Rc and Hb is described by the equation Rc =
      0.2203Hb + 2.4775, with a correlation coefficient of 0.9905.

PMID- 30118950
TI  - "It's about having money, but also happiness:" A qualitative investigation of how
      adolescents understand subjective status in themselves and others.
AB  - INTRODUCTION: Understanding why adolescent subjective assessments of status
      matter to their psychosocial outcomes over and above objective assessments of
      socioeconomic status (SES) requires a better comprehension of how adolescents
      construct status in themselves and others. Using a qualitative approach, the goal
      of the current study was to better understand what factors adolescents use to
      assign status, and how their perceptions of this status vary according to their
      own SES. METHOD: Qualitative interviews were conducted with 32 adolescents from
      Quebec, Canada, from varied socioeconomic backgrounds. In particular, they were
      shown the ladder from the Subjective Social Status Scale and asked what defined
      scale placement in their communities. They were also asked where they would place
      themselves on this scale, and why. RESULTS: The importance of traditional
      indicators of SES such as money, educational level, and occupational prestige
      were underlined by almost all adolescents, but other factors (e.g., wellbeing,
      family life, values concerning work, other-orientation, or rule-following) were
      also frequently discussed. Adolescents used similar criteria in the placement of
      themselves and others. Contradictions often emerged, however, as adolescents'
      scale placement was often higher than what would be expected based on traditional
      SES indicators. CONCLUSIONS: These findings provide a starting point for
      understanding why adolescents' subjective assessments of status may matter above
      and beyond traditional assessments of SES, and how we can better measure this
      construct.

PMID- 30118949
TI  - Quantum changes in self-efficacy and condom-use intention among youth: A chained
      cusp catastrophe model.
AB  - INTRODUCTION: The complex relationships among HIV knowledge, condom-use skills,
      self-efficacy, peer influence and intention to use condoms have been rigorously
      investigated. However, studies guided by a linear behavior change model often
      explain only a limited amount of variances. This study aims to advance our
      understanding of the relationships through a nonlinear quantum change paradigm.
      METHODS: Data (n = 1970, 40.61% male, mean age 16.94 +/- 0.74) from a behavioral
      intervention program among high school students in the Bahamas were analyzed with
      a chained cusp catastrophe model in two steps. In the first step, self-efficacy
      was analyzed as the outcome with HIV knowledge/condom-use skills as asymmetry
      variables and peer influence as bifurcation variable. In the second step, condom
      use intention was analyzed as the outcome while self-efficacy (outcome in the
      first step) was used as bifurcation variable allowing peer influence as
      bifurcation, and HIV knowledge/condom-use skills were included as asymmetry. Cusp
      modeling analysis was conducted along with equivalent linear models. RESULTS: The
      cusp model performed better than the linear and logistic models. Cusp modeling
      analyses revealed that peer influence significantly bifurcated the relationships
      between HIV knowledge/condom-use skills and self-efficacy; while both self
      efficacy and peer influence significantly bifurcated the relationship between HIV
      knowledge/condom-use skills and condom-use intention. CONCLUSION: Our findings
      support the central role of self-efficacy and peer influence as two chains in
      bridging the complex quantum relationships between HIV knowledge/condom-use
      skills and condom-use intention among adolescents. The nonlinear cusp catastrophe
      modeling provided a new method to advance HIV behavioral research.

PMID- 30118951
TI  - Stochastic evaluation of Salmonella enterica lethality during thermal
      inactivation.
AB  - Stochastic models take into account the uncertainty and variability of
      predictions in quantitative microbial risk assessment. However, a model that
      considers thermal inactivation conditions can better predict whether or not
      bacteria in food are alive. To this end, we describe a novel probabilistic
      modelling procedure for accurately predicting thermal end point, in contrast to
      conventional kinetic models that are based on extrapolation of the D value. We
      used this new model to investigate changes in the survival probability of
      Salmonella enterica serotype Oranienburg during thermal processing. These changes
      were accurately described by a cumulative gamma distribution. The predicted total
      bacterial reduction time with a survival probability of 10-6-the commercial
      standard for sterility-was significantly shorter than that predicted by the
      conventional deterministic kinetic model. Thus, the survival probability
      distribution can explain the heterogeneity in total reduction time for a
      bacterial population. Furthermore, whereas kinetic methodologies may overestimate
      the time required for inactivation, our method for determining survival
      probability distribution can provide an accurate estimate of thermal inactivation
      and is therefore an important tool for quantitative microbial risk assessment of
      foods.

PMID- 30118952
TI  - Evaluation of Daphnia magna metabolic responses to organic contaminant exposure
      with and without dissolved organic matter using 1H nuclear magnetic resonance
      (NMR)-based metabolomics.
AB  - Previous studies have shown that contaminant toxicity to target organisms is
      altered by the presence of dissolved organic matter (DOM). Contaminants can bind
      to DOM and this may alter the bioavailability and subsequent toxicity of the
      contaminants. However, molecular-level techniques are needed to more closely
      evaluate the impact of DOM on the sub-lethal biochemical responses to emerging
      contaminants. To investigate how DOM may alter the metabolic response to organic
      contaminant exposure, 1H nuclear magnetic resonance (NMR)-based metabolomics was
      used to investigate how the metabolome of Daphnia magna changes when Suwannee
      River DOM (5 mg organic carbon/L) is included in the acute exposure of four
      contaminants with varying hydrophobicity. Sub-lethal concentrations of the
      hydrophobic contaminant 17alpha-ethynylestradiol (EE2), the relatively more polar
      compounds carbamazepine and imidacloprid, or the anionic contaminant
      perfluorooctane sulfonate (PFOS) were used. A 48-h exposure to DOM alone had a
      minor impact on the metabolome of D. magna. There were significant increases in
      amino acids from EE2 exposure which were reduced in the presence of DOM,
      suggesting that DOM may alleviate the sub-lethal metabolic response from EE2
      exposure through sorption and a reduction in freely dissolved EE2. The metabolome
      was relatively unaltered with exposure to carbamazepine and imidacloprid in the
      presence of DOM which is likely because these contaminants are water soluble and
      did not strongly interact with DOM. PFOS exposure resulted in a more significant
      metabolic response with DOM suggesting that DOM enhanced the uptake and
      bioavailability of PFOS in D. magna. As such, the presence of DOM should be
      considered when determining sensitive molecular-level changes in organisms to sub
      lethal organic contaminant exposure.

PMID- 30118953
TI  - Hydrogen sulfide inhalation-induced immune damage is involved in oxidative
      stress, inflammation, apoptosis and the Th1/Th2 imbalance in broiler bursa of
      Fabricius.
AB  - Hydrogen sulfide (H2S) is widely accepted to be a signaling molecule that
      exhibits some potentially beneficial therapeutic effects at physiological
      concentrations. At elevated levels, H2S is highly toxic and has a negative effect
      on human health and animal welfare. Studies have shown that H2S exposure induces
      an immune function in mice, but there are few studies of the effect of continuous
      H2S exposure on immune organs in poultry. In this study, one-day-old broilers
      were selected and exposed to 4 or 20 ppm of H2S gas for 14, 28 and 42 days of
      age. After exposure, the bursa of Fabricius (BF) was harvested. The results
      showed that continuous H2S exposure reduced the body weight, abdominal fat
      percentage, and antibody titer in broilers. H2S exposure also decreased mRNA
      expression of IgA, IgM and IgG in the broiler BF. A histological study revealed
      obvious nuclear debris, and a few vacuoles in the BF, and an ultrastructural
      study revealed mitochondrial and nuclear damage to BF cells after H2S exposure
      for 42 d. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling
      (TUNEL) assay suggested H2S exposure remarkably increased the number of TUNEL
      positive nuclei and significantly increased apoptotic index. The expression of
      apoptotic genes also confirmed that H2S inhalation damaged the broiler BF.
      Increased cytokines and reduced antioxidant responses were detected in the BF
      after exposure to H2S. Cytokines promoted inflammation and caused a Th1/Th2
      imbalance. We suggest that continuous H2S intoxication triggers oxidative stress,
      inflammation, apoptosis and a Th1/Th2 imbalance in the BF, leading to immune
      injury in broilers.

PMID- 30118954
TI  - Contamination and ecological risks of toxic metals in the Hai River, China.
AB  - Contamination of trace metals in urban rivers is a global problem. The objective
      of this study was to investigate the contamination and ecological risks of trace
      metals in the Hai River, which receives substantial effluents from the Beijing
      Tianjin region. A total of 43 surface water and sediment samples were collected
      and analyzed for physiochemical properties and toxic elements. The concentrations
      of Cd, Cr, Ni, Pb, Cu and Zn in the river water met the Chinese environmental
      quality grade I standards for surface water. The average total concentrations of
      Zn, Cr, V, Cu, Pb, Ni, Co, Sc and Cd in the sediments were 144.2, 77.5, 70.1,
      46.1, 40.1, 29.6, 12.4, 9.9 and 0.26 mg/kg, respectively. The enrichment of Cd,
      Cr, Cu, Pb and Zn in the sediments was influenced by anthropogenic activity, as
      indicated by the enrichment factor (EF) and multivariate analysis. The
      concentrations of Co and Cr in the sediments were predominantly in residual
      fractions, while relatively higher amounts of Cd, Pb, Zn and Cu were in non
      residual fractions. There was a significant correlation between concentrations of
      Cd, Co, Cr, Cu, Pb and Zn in non-residual fractions and their corresponding EF
      values (P < 0.01). This result further demonstrated that anthropogenic inputs
      were an important contributor to metal enrichment. The high bioavailability of Cd
      and poor bioavailability of Co and Cr in the sediments were demonstrated by the
      single extraction procedure. The significant correlation between concentrations
      of Cd, Cu, Pb and Zn in non-residual fractions and their concentrations in EDTA
      extractable fractions was established (P < 0.01). This result indicates that
      single-step EDTA extraction may represent a useful procedure for assessing the
      bioavailability of Cd, Cu, Pb and Zn in riverine sediments. The ecological risks
      of the metals studied in the Hai River sediments were at a low level, dominated
      by the risks imposed by Cd.

PMID- 30118955
TI  - Removal of tridecane dicarboxylic acid in water by nanoscale Fe0/Cu0 bimetallic
      composites.
AB  - In this study, nanoscale zerovalent Fe0/Cu0 bimetallic composites were
      synthesized by liquid-phase reduction of Fe(II)/Cu(II) and applied for
      decomposition of tridecane dicarboxylic acid (DC13). The removal performance of
      Fe0/Cu0 bimetallic composites for DC13 in terms of Fe/Cu ratios, addition amount,
      reaction time and initial pH were studied. The as-prepared nanoscale composites
      were characterized by a transmission electron micrographs (TEM), scanning
      electron microscopy (SEM), X-ray diffraction (XRD), BET surface area, fourier
      transform infrared spectroscopy (FT-IR) and inductively coupled plasma-atomic
      emission spectrometry (ICP). Finally, the degradation mechanisms of DC13
      utilizing the Fe0/Cu0 nanocomposites were investigated by using mass spectrumetry
      (MS). The results indicated that the Fe0/Cu0 bimetallic composites exerted a
      remarkable removal capacity for DC13 through the multiple reactions, e.g.,
      coagulation, adsorption and *OH reduction in the Fe0/Cu0 system. XPS indicated
      that the Fe0/Cu0 reduction reaction of hydroxyl radicals (*OH) system played a
      significant role in degradation of DC13 and the LC-MS result suggested that DC13
      was degraded into inorganic small molecules by *OH radicals generated from the
      corrosion of Fe0. The experimental results indicated that the nanoscale Fe0/Cu0
      could be used as a potential material to remove DC13 because of its remarkable
      degradability.

PMID- 30118956
TI  - Identification of anthropogenic inputs of trace metals in lake sediments using
      geochemical baseline and Pb isotopic composition.
AB  - Source identification of trace metals in the water environment is important in
      understanding its environmental behavior and in the prevention and remediation of
      further pollution. Here, the regional geochemical baseline (RGB) and Pb isotopic
      ratios are combined to decipher the anthropogenic contribution rate, main
      anthropogenic source, and transport pathway of trace metals in sediments
      collected from the largest freshwater lake in northern China, Baiyangdian (BYD)
      Lake. The established RGB values of Cr, Ni, Cu, Zn, Cd, and Pb were 63.0, 27.8,
      24.7, 46.1, 0.18, and 22.0 mg/kg, respectively, which were slightly different
      from the regional soil background values. Based on the RGB and actual
      concentrations of trace metals in the lake sediments, the calculated average
      anthropogenic contribution were lower than 20% except for Cd. Compared with the
      other trace metals, Cd was the element most impacted by anthropogenic input,
      which was mainly caused by the point source pollution in some sites. The risk
      assessment (geo-accumulation index and potential ecological risk) using the RGB
      as the regional background values showed that BYD sediments were uncontaminated
      by the trace metals, and at low ecological risk from the trace metals. The
      results of these two risk assessments further validated the assessment of the
      anthropogenic contribution by the RGB. In addition, Pb isotopic ratios result
      showed that coal combustion was the main potential source of anthropogenic Pb in
      the BYD sediments and atmospheric deposition was the main transport pathway. This
      study tried to combine the geochemical baseline and Pb isotopic composition to
      identify the anthropogenic input of trace metals in the sediments. It will
      provide a new insight into assessing the anthropogenic contributions, identifying
      the main anthropogenic sources, and transport pathways of trace metals in water
      environment.

PMID- 30118957
TI  - Modelling benzene series pollutants (BTEX) build-up loads on urban roads and
      their human health risks: Implications for stormwater reuse safety.
AB  - Benzene series compounds (BTEX) are toxic pollutants primarily generated by
      traffic activities in an urban environment. BTEX pollutants can be deposited
      (build-up) on urban road surfaces during dry periods and then washed-off into
      stormwater runoff. Since BTEX pollutants can pose high human health risks, they
      can undermine stormwater reuse safety after they enter stormwater runoff. In this
      study, the BTEX pollutants build-up loads on urban road surfaces were
      investigated in Shenzhen, China. An artificial neural network (ANN) approach and
      two conventional regression modelling approaches were compared in terms of
      estimating BTEX build-up loads based on land use related parameters. It was found
      that the ANN approach had a better performance than the two regression modelling
      approaches. Additionally, the spatial distribution maps and human health risk map
      of BTEX pollutants build-up created using the ANN approach can provide a robust
      visualization platform to identify 'hot-spot' areas. These areas have a potential
      to generate highly BTEX polluted stormwater runoff and hence be inappropriate to
      be reused. These research outcomes are expected to provide an effective approach
      for ensuring stormwater reuse safety and a useful guidance for decision-making
      for stormwater management and water environment protection related urban
      planning.

PMID- 30118958
TI  - A single cell transcriptional portrait of embryoid body differentiation and
      comparison to progenitors of the developing embryo.
AB  - Directed differentiation of pluripotent stem cells provides an accessible system
      to model development. However, the distinct cell types that emerge, their
      dynamics, and their relationship to progenitors in the early embryo has been
      difficult to decipher because of the cellular heterogeneity inherent to
      differentiation. Here, we used a combination of bulk RNA-Seq, single cell RNA
      Seq, and bioinformatics analyses to dissect the cell types that emerge during
      directed differentiation of mouse embryonic stem cells as embryoid bodies and we
      compared them to spatially and temporally resolved transcriptional profiles of
      early embryos. Our single cell analyses of the day 4 embryoid bodies revealed
      three populations which had retained related yet distinct pluripotent signatures
      that resemble the pre- or post-implantation epiblast, one population of
      presumptive neuroectoderm, one population of mesendoderm, and four populations of
      neural progenitors. By day 6, the neural progenitors predominated the embryoid
      bodies, but both a small population of pluripotent-like cells and an anterior
      mesoderm-like Brachyury-expressing population were present. By comparing the day
      4 and day 6 populations, we identified candidate differentiation paths,
      transcription factors, and signaling pathways that mark the in vitro correlate of
      the transition from the mid-to-late primitive streak stage.

PMID- 30118959
TI  - Kinetics and growth mechanism of the photoinduced synthesis of silver
      nanoparticles stabilized with lysozyme.
AB  - A fast and single-step procedure is reported for the preparation of stable
      solutions of spherical-shaped silver nanoparticles (AgNPs) coated with lysozyme
      (LZ). The preparation of the AgNP@LZ nanocomposites was based on the reduction of
      Ag+ with ketyl radicals photo-generated by the UVA-photolysis of the benzoin I
      2959. Both reaction precursors bind to LZ, modifying its superficial charge and
      conformational structure. The photo-induced kinetics of formation of the AgNPs as
      a function of the LZ concentration was monitored in-situ by UV-vis absorption
      spectroscopy. The multivariate curve resolution-alternating least square (MCR
      ALS) method was used for the deconvolution of the kinetic curves for each
      transient species formed before the growth of the final AgNPs colloids. The
      Kolmogorov-Johnson-Mehl-Avrami (KJMA) model to describe the formation of the
      AgNPs was used, and the respective first-order rate constants for the growth of
      the AgNPs as a function of the lysozyme concentration were calculated and the
      role of the protein capping in the growth kinetics was evaluated. Despite the
      protein being partially oxidized by the photo-generated radicals, it was strongly
      adsorbed onto the silver surface forming a tight coating shell around the AgNPs
      of approximately 30-60 protein molecules. As a result of the partial denaturation
      and crowded packing, its intrinsic lytic activity was strongly reduced.

PMID- 30118960
TI  - Ingested microplastic as a two-way transporter for PBDEs in Talitrus saltator.
AB  - The presence and accumulation of plastic waste into the marine environment are
      well known environmental issues. Microplastics (MPs) end up in sea waters and,
      due to their hydrophobicity and high surface/volume ratio, POPs tend to sorb and
      accumulate to their surface. The supralittoral amphipod Talitrus saltator (T.
      saltator) was selected to study the role of MPs in the transfer of organic
      pollutants and to investigate if ingested MPs could either transfer contaminants
      to biota or clean it adsorbing pollutants taken from the diet. T. saltator is an
      established POPs (Persistent Organic Pollutants) biomonitor in coastal
      environments and it is able to swallow microplastics in natural condition. Two
      laboratory experiments were performed and T. saltator was exposed to a labelled
      polybrominated diphenyl ether (13C-labelled BDE-47) to investigate the opposite
      gradient role of MPs. X Ray Micro-CT (Micro-Computed Tomography) analyses were
      also performed on sandhopper samples to evaluate the uptake of MPs via digestive
      tract. The results showed that MPs ingestion could whether transfer and remove
      contaminants from T. saltator, indicating a partial balance among positive and
      negative effects. This study has underlined MP potential double role
      demonstrating that MP can act both as a carrier and scavenger for the
      bioaccumulation of organic pollutants (i.e. PBDEs), suggesting that chemicals
      leaching from MPs could have a limited impact to biota.

PMID- 30118962
TI  - A giant pulmonary cyst hydatid imitating plevral effusion.
AB  - INTRODUCTION: Cystic echinococcosis is an endemic disease in east Turkey.
      Echinococcosis granulosus is reported as the most common agent of cystic
      echinoccocus. Hydatid cysts are generally involved in lung and liver.
      PRESENTATION OF CASE: 37 year old female admitted to our clinic with cough and
      expectoration of watery material progressing within 3 months. Thorax CT
      demonstrated a 110*100 mm well defined cavitary lesion in the right lower lobe of
      the lung. The patient was treated with cystotomy & capitonnage and postoperative
      albendazole treatment successfully. DISCUSSION: Hydatid cysts should be conceived
      in differential diagnosis of pulmonary cystic lesions. CONCLUSIONS: The basic
      treatment for cystic echinococcosis is surgery. Postoperative antihelminthic
      therapy is preferred to prevent postoperative complications.

PMID- 30118961
TI  - Would Marjolin see it coming? Two unusual cases of squamous cell carcinoma.
AB  - INTRODUCTION: Cutaneous squamous cell carcinoma (SCC) is a common skin cancer,
      second in incidence only to basal cell carcinoma (BCC). The incidence of SCC
      increases significantly with age; thus, it is rarely diagnosed in young patients.
      In this paper, we present two cases of young patients who presented clinically
      with purulent lesions that were later diagnosed as large primary SCCs. MATERIALS
      AND METHODS: A review of the medical records of two patients who were admitted to
      the department of plastic surgery with a final clinical diagnosis of cutaneous
      SCC was conducted. Information of the review included history, physical
      examination, laboratory tests, imaging studies and histology. A literature review
      was also conducted and discussed. RESULTS: Two female patients under the age of
      45 presented with large, purulent lesions that were initially clinically
      suggestive of an infectious etiology. The lesions were surgically treated by
      incision and drainage without sending tissue samples to pathology. Biopsies of
      the lesions were performed to obtain a tissue diagnosis due to recurrence
      approximately one year after the initial treatment. Histological evaluation
      revealed well differentiated squamous cell carcinomas. Surgical intervention with
      wide excision with adjuvant chemotherapy was recommended based on biopsy and CT
      scan results. DISCUSSION: Aggressive behavior of SCC in young patients is
      uncommon. The patients in this report were diagnosed only one year after the
      first sign of the lesion. One patient was first diagnosed with an abscess, and
      the other with necrotizing fasciitis. The delayed diagnosis of SCC in these two
      patients is a potential contributing factor to the aggressiveness of the tumors.
      Therefore, it is imperative to perform skin biopsies of chronic or persistent
      purulent lesions to rule out malignancies including Marjolin's ulcer. CONCLUSION:
      Aggressive SCC should be suspected in cases of persistent and relapsing purulent
      lesions in all patients.

PMID- 30118963
TI  - Acute dacryocystitis complicated by orbital cellulitis and loss of vision: A case
      report and review of the literature.
AB  - INTRODUCTION: Acute dacryocystitis usually presents as a pre-septal cellulitis
      since the lacrimal sac lies anterior to the orbital septum. Orbital cellulitis
      secondary to acute dacryocystitis is very rare due to a variety of anatomic
      barriers to the orbit but can occur and result in abscess formation with risk of
      visual compromise. PRESENTATION OF CASE: We describe a case of otherwise healthy
      adult who presented with complete visual loss following orbital cellulitis and
      abscess formation secondary to acute dacryocystitis. The clinical, radiological,
      intraoperative and postoperative findings are discussed. DISCUSSION: Typically,
      orbital cellulitis responds well to systemic antibiotic and surgical drainage
      without permanent visual loss. There are 7 cases reported in the literature of
      acute dacryocystitis complicated by permanent visual loss. CONCLUSION: Patients
      with acute dacryocystitis need to be carefully monitored for signs of orbital
      cellulitis. Prompt recognition and appropriate treatment of this condition are
      essential.

PMID- 30118965
TI  - Clinical and genetic signatures of local recurrence in oral squamous cell
      carcinoma.
AB  - PURPOSE: Recurrent and metastatic Oral Squamous Cell Carcinoma (OSCC) is often
      incurable. There are large gaps in the understanding of the clinical course,
      biology and genetic biomarkers of OSCC which could help us identify patients with
      high-risk of recurrence who may benefit from intensified therapy or novel
      targeted therapy trials. The purpose of this study was to identify significant
      clinical, pathological and genomic risk factors for local recurrence in OSCC.
      PATIENTS AND METHODS: Molecular data sets and clinicopathological characteristics
      of 159 head and neck carcinoma patients were obtained from The Cancer Genome
      Atlas (TCGA) data portal and analyzed using the Genome Data Analysis Center and
      cBioPortal to find significant risk factors for tumor recurrence. RESULTS: The
      local recurrence rate was 24%. OSCC originating from the buccal mucosa composed
      13% of all the tumors in the recurrent group, making it a statistically
      significant risk of recurrence (P value = 0.03). Likewise, positive surgical
      margins, pathological T staging, and alcohol consumption were found to be
      significantly associated with recurrence (P value < 0.05). Genetic profiling
      revealed the top 5 mutated genes (using the MutSigCV analysis). Only one of these
      genes, CASP8 was the only gene that was significantly altered only in the
      recurrent group (Q value = 8.7 * 10-11). The fingerprint of 5 mutated genes was
      found in 97% of the patients in the recurrence group. Moreover, copy number
      alterations in cytoband 5p15.33, which involved amplification in telomerase
      reverse-transcriptase (TERT) gene, was found to be significant only in the
      recurrent group. CONCLUSIONS: In the current study, we found several clinical and
      genetic characteristics that could define patients with high-risk of OSCC
      recurrence. This provides a means of identifying patients that may benefit from
      intensified therapy or novel targeted therapy trials.

PMID- 30118964
TI  - Apremilast prevent doxorubicin-induced apoptosis and inflammation in heart
      through inhibition of oxidative stress mediated activation of NF-kappaB signaling
      pathways.
AB  - BACKGROUND: Doxorubicin is an effective, potent and commonly used anthracycline
      related anticancer drug; however, cardiotoxicity compromises its therapeutic
      potential. Apremilast, a novel phosphodiesterase type 4-inhibitor, reported to
      have anti-inflammatory effects and modulating many inflammatory mediators.
      METHODS: The present study investigated the influence of apremilast against
      doxorubicin-induced cardiotoxicity in male Wistar rats. A total, 24 animals were
      divided into four groups of six animal each. Group 1, served as control and
      received normal saline. Group 2 animals, received doxorubicin (20mgkg-1, ip).
      Group 3 and 4, treatment group, received doxorubicin (20mgkg-1, ip) with the same
      schedule as group-2, plus apremilast (10 and 20mgkg-1day-1, po) respectively.
      Oxidative stress, caspase-3 enzyme activity, gene expression and protein
      expression were tested. RESULTS: The results of the present study demonstrated
      that administration of apremilast reversed doxorubicin-induced cardiotoxicity.
      CONCLUSION: These findings suggested that apremilast can attenuate doxorubicin
      induced cardiotoxicity via inhibition of oxidative stress mediated activation of
      nuclear factor-kappa B signaling pathways.

PMID- 30118966
TI  - Learning to focus on number.
AB  - With age and education, children become increasingly accurate in processing
      numerosity. This developmental trend is often interpreted as a progressive
      refinement of the mental representation of number. Here we provide empirical and
      theoretical support for an alternative possibility, the filtering hypothesis,
      which proposes that development primarily affects the ability to focus on the
      relevant dimension of number and to avoid interference from irrelevant but often
      co-varying quantitative dimensions. Data from the same numerical comparison task
      in adults and children of various levels of numeracy, including Mundurucu Indians
      and western dyscalculics, show that, as predicted by the filtering hypothesis,
      age and education primarily increase the ability to focus on number and filter
      out potentially interfering information on the non-numerical dimensions. These
      findings can be captured by a minimal computational model where learning consists
      in the training of a multivariate classifier whose discrimination boundaries get
      progressively aligned to the task-relevant dimension of number. This view of
      development has important consequences for education.

PMID- 30118967
TI  - Effects of induced appearance-related interpretation bias: A test of the
      cognitive-behavioral model of body dysmorphic disorder.
AB  - BACKGROUND AND OBJECTIVES: Interpretation biases are hypothesized to maintain
      body dysmorphic disorder (BDD). Although their existence and malleability have
      been investigated in clinical studies, their causal status in the maintenance of
      BDD remains unclear. This study examined the effects of a single-session
      appearance-related interpretation bias training (CBM-I) on bias indices and
      stress reactivity (i.e., distress, appearance dissatisfaction, self-esteem,
      perceived physical attractiveness), exploring the causality predicted in
      cognitive-behavioral models. METHODS: We used a modified version of the Word
      Sentence Association Paradigm (WSAP), assessing explicit (i.e., decision rates)
      and more implicit interpretation bias components (i.e., reaction times). Mentally
      healthy students (N = 112) were randomized to training conditions enhancing
      positive interpretation patterns (PT) vs. negative interpretation patterns (NT)
      vs. a no-feedback control condition (CC). Stress reactivity was assessed during
      the Cyberball Paradigm. RESULTS: The PT showed a pre-post increase in adaptive
      bias patterns regarding decision and a differential pre-post decrease in reaction
      times for the rejection of negative interpretations, compared to the other
      groups. There were no condition-congruent post-training differences in stress
      reactivity. However, residual interpretation bias change was significantly
      correlated with state distress, self-esteem and appearance dissatisfaction during
      stressor exposure. LIMITATIONS: Limitations pertaining to sample characteristics,
      training and assessment overlap, and stressor task design are discussed.
      CONCLUSIONS: Findings suggest that appearance-related interpretation bias is
      modifiable both explicitly and more implicitly via CBM-I in a mentally healthy
      sample. The causal status of interpretation bias in BDD maintenance warrants
      further investigation.

PMID- 30118968
TI  - High-throughput microfluidic imaging flow cytometry.
AB  - Recently, microfluidic-based flow cytometry platforms have been shown to be
      powerful tools for the manipulation and analysis of single cells and micron-sized
      particles in flow. That said, current microfluidic flow cytometers are limited in
      both their analytical throughput and spatial resolution, due to their reliance on
      single point interrogation schemes. Conversely, high-speed imaging techniques can
      be applied to a wide variety of problems in which analyte molecules are
      manipulated at high linear velocities. Such an approach allows a detailed
      visualization of dynamic events through acquisition of a series of image frames
      captured with high temporal and spatial resolution. Herein, we describe some of
      the most significant recent advances in the development of multi-parametric,
      optofluidic imaging flow cytometry for the enumeration of complex cellular
      populations.

PMID- 30118969
TI  - Predictors of psychological recommendations in child protection evaluation.
AB  - Child protection matters from an important social and legal challenge, in which
      psychologists may be called upon to address a series of questions relevant for
      judicial decision-making. In an explorative manner, the current study
      investigates variables that influence psychological evaluators' recommendations
      in child protection cases. The data is based on a quantitative content review of
      103 psychological evaluation reports, conducted at an institute of forensic
      psychology in Germany. Using bivariate and logistic regression analyses, the
      following predictors were analyzed in this study: Child-related factors, familial
      risk factors, and general custody criteria. The outcome measure was the
      evaluator's recommendation regarding long-term placement of the child and long
      term custody arrangements. Evaluators were more likely to recommend permanent
      foster placement if the child showed insecure or disorganized attachment
      patterns, especially when combined with developmental delays, or if the child was
      temporarily in institutional or foster placement at the time of evaluation. The
      results support the conclusion that the most important factors for psychological
      expert recommendations refer to the "harm of the child" criterion in terms of
      developmental and psychological maladaptation.

PMID- 30118970
TI  - Society, individual, family, and school factors contributing to child mental
      health in war: The ecological-theory perspective.
AB  - Mental health problems are common in war-affected areas, but children have
      different levels of vulnerability. Based on ecological theory (Bronfenbrenner,
      2005), this study analyses how factors related to the child (cognitive capacity),
      their family (parental depression and parenting styles), and their school
      (teachers' practices and peer relations) mediate the association between
      traumatic stress (traumatic war experiences and stressful life-events) and child
      mental health (posttraumatic stress and psychological distress symptoms). The
      participants were 303 Palestinian children (51.2% girls) of 10-13 years (M =
      10.94 +/- 0.50) and their parents from the Gaza Strip. The children filled in
      questionnaires during school classes and the parents did so at their homes. The
      results of structural equation modeling substantiated the hypothesis that
      parental depression, poor parenting and low-quality peer relations mediated
      between traumatic stress and children's mental health problems. Contrary to the
      hypothesis, child-related factors did not mediate that association. To conclude,
      parents and peers provide important age-salient social resources for children in
      war conditions, and psychosocial interventions should therefore enhance their
      beneficial functions.

PMID- 30118971
TI  - Non-adult child supervision practices in Lao People's Democratic Republic.
AB  - Researchers have paid little attention to non-adult child supervision and the
      prevalence and factors influencing this practice in low-income countries. A
      better understanding of this phenomenon is needed to inform the development and
      implementation of policies and interventions to enhance child supervision in
      those settings. This study explores the prevalence and factors associated with
      young children being home alone or under the care of another young child in Lao
      People's Democratic Republic. Using the 2011-2012 Lao Social Indicator Survey (N
      = 10,740 for the subsample of 'child was home alone' and N = 10,539 for the
      subsample of 'child cared by another child < 10 years of age'), multi-level
      Poisson regressions were performed to determine the number of days children under
      five years of age were home alone or under the care of another child younger than
      10 years of age. Large discrepancies across provinces and between urban and rural
      populations within each province were found. Children living in rural areas were
      more than five times more likely to be unsupervised than children living in urban
      settings (incidence rate ratio, IRR 5.2; 95% CI: 1.8-15.2), and children living
      in rural areas were nearly twice more likely to be under the care of another
      child than children living in urban settings (IRR 1.9; 95% CI: 1.3-2.8). Age was
      also a common factor in explaining variation in both dependent variables.
      Policies aimed at facilitating adequate child care and supervision should
      consider rurality to increase children's protection.

PMID- 30118972
TI  - A review of opioid addiction genetics.
AB  - Opioid use disorder (OUD) affects millions of people worldwide and the risk of
      developing the disorder has a significant genetic component according to twin and
      family studies. Identification of the genetic variants underlying this inherited
      risk has focused on two different methods: candidate gene studies and genome-wide
      association studies (GWAS). The most studied candidate genes have included the mu
      opioid receptor (OPRM1), the delta-opioid receptor (OPRD1), the dopamine D2
      receptor (DRD2), and brain-derived neurotrophic factor (BDNF). Variants in these
      genes have been associated with relatively small, but reproducible, effects on
      OUD risk. More recently, GWAS have identified potential associations with
      variants in KCNG2, KCNC1, CNIH3, APBB2, and RGMA. In total the genetic
      associations identified so far explain only a small portion of OUD risk. GWAS of
      OUD is still in the early stages when compared to studies of other psychiatric
      disorders, such as schizophrenia, which have found many relevant variants with
      small effect sizes only after large meta-analyses. Substantial increases in
      cohort sizes will likely be necessary in the OUD field to achieve similar
      results. In addition, it will be important for future studies of OUD to
      incorporate rare variants, epigenetics, and gene * environment interactions into
      models in order to better explain the observed heritability.

PMID- 30118973
TI  - Versatile applications of freshwater and marine water microalgae in dairy
      wastewater treatment, lipid extraction and tetracycline biosorption.
AB  - In this study, freshwater (Scenedesmus quadricauda, Sq) and marine water
      (Tetraselmis suecica, Ts) microalgae were used for the treatment of dairy
      wastewater (DWW). Sq and Ts showed the highest biomass productivity as 0.47 and
      0.61 g/L, respectively. Removal efficiencies of total nitrogen (TN), phosphate
      (PO43-), and total organic carbon (TOC) were observed as 86.21, 89.83 and 64.47%
      by Sq and 44.92, 42.18 and 40.16% by Ts, respectively. After wastewater
      treatment, lipids were extracted from microalgal biomasses. Fatty acid methyl
      esters (FAMEs) analysis revealed that saturated fatty acids (SFAs) are dominant
      in Sq and polyunsaturated fatty acids (PUFAs) in Ts. After lipid extraction,
      removal of tetracycline (TC) from water by microalgal biomasses was also
      investigated. Maximum adsorption capacities of Sq and Ts were found to be 295.34
      and 56.25 mg/g, respectively. Results of this study revealed the versatile
      applications of microalgae for wastewater treatment, lipid production and TC
      removal from water.

PMID- 30118974
TI  - Interpreting the effects of natural organic matter on antimicrobial activity of
      Ag2S nanoparticles with soft particle theory.
AB  - Natural organic matter (NOM) ubiquitously exists in natural waters and would
      adsorb onto the particle surface. Previous studies showed that NOM would
      alleviate the toxicity of nanomaterials, while the mechanism is seldom
      quantitatively interpreted. Herein, the effects of humic substances [Suwannee
      River fulvic acid (SRFA) and Suwannee River humic acid (SRHA)] and
      biomacromolecules [alginate and bovine serum albumin (BSA)] on the aggregation
      and antimicrobial effects of silver sulfide nanoparticles (Ag2S-NPs) were
      investigated. The aggregation kinetics of Ag2S-NPs in electrolyte solutions were
      in agreement with the results based on Derjaguin-Landau-Verwey-Overbeek (DLVO)
      theory. The dynamic light scattering (DLS) results showed that the SRFA, SRHA,
      alginate and BSA molecules coated on the Ag2S-NPs surfaces. The NOM coating layer
      prevented salt-induced coagulation of Ag2S-NPs, and the effects of BSA and SRHA
      on Ag2S-NPs stabilizing were more obvious than that of SRFA and alginate. Flow
      cytometry analysis results suggested that BSA and SRHA were more effective on
      alleviating the Ag2S-NPs induced cell (Escherichia coli) membrane damage than
      SRFA and alginate. After interpreting the electrophoretic mobility (EPM) data of
      the NOM coated Ag2S-NPs by Ohshima's soft particle theory, it was found that the
      thickness of the NOM coating layers followed the orders of BSA > SRHA > alginate
      > SRFA. The E.coli cell membrane damage level was negatively correlated with the
      thickness and softness of the coating layer. NOM coating may physically alleviate
      the contact between NPs and E. coli cells and thus attenuate the extent of cell
      membrane damage caused by the NP-cell interaction. This work provides a new
      perspective for quantitatively interpreting the influence of NOM on the
      environmental behaviors and risks of nanomaterials.

PMID- 30118975
TI  - Distribution, abundance and activity of geosmin and 2-methylisoborneol-producing
      Streptomyces in drinking water reservoirs.
AB  - While cyanobacteria have been widely recognised as the most common cause of
      geosmin and 2-methylisoborneol related taste and odour (T&O) episodes in drinking
      water supplies, many reported occurrences could not be attributed to these
      organisms. The Streptomyces genus of soil bacteria also includes producers of
      these compounds, however their potential role in such occurrences is poorly
      understood and often disregarded on the basis that they are terrestrial rather
      than aquatic organisms, with their detection in water samples assumed to reflect
      the presence of dormant spores rather than metabolically active vegetative cells.
      Using qPCR and a differential cell lysis technique for DNA extraction, allowing
      distinction of spores from vegetative cells, the aim of this study was to
      determine the distribution, abundance and potential activity of Streptomyces
      species across a range of aquatic and marginal habitat zones in two drinking
      water reservoirs, including: exposed soil, submerged sediments, plant debris and
      emergent macrophytes at the margins; marginal and offshore surface waters; deep
      offshore waters; and offshore benthic sediments. Marginal substrates including
      soil, sediment and plant debris were identified as the dominant habitat zones for
      Streptomyces, (concentrations up to 1.1 * 107 cells g-1) supporting the concept
      of 'wash-in' from the margins due to run-off or water level rise following
      rainfall, as the likely pathway for Streptomyces induced T&O in reservoirs.
      However, vegetative cells were also found to comprise a substantial proportion of
      Streptomyces populations in the reservoir water mass itself (>90% in some surface
      and bottom water samples), suggesting the potential for these bacteria to be
      metabolically active in the water and therefore contribute to in situ production
      of T&O metabolites.

PMID- 30118976
TI  - First insights into the living groundwater mycobiome of the terrestrial
      biogeosphere.
AB  - Although fungi play important roles in biogeochemical cycling in aquatic
      ecosystems and have received a great deal of attention, much remains unknown
      about the living fractions of fungal communities in aquifers of the terrestrial
      subsurface in terms of diversity, community dynamics, functional roles, the
      impact of environmental factors and presence of fungal pathogens. Here we address
      this gap in knowledge by using RNA-based high throughput pair-end illumina
      sequencing analysis of fungal internal transcribed spacer (ITS) gene markers, to
      target the living fractions of groundwater fungal communities from fractured
      alternating carbonate-/siliciclastic-rock aquifers of the Hainich Critical Zone
      Exploratory. The probed levels of the hillslope multi-storey aquifer system
      differ primarily in their oxygen and nitrogen content due to their different
      connections to the surface. We discovered highly diverse living fungal
      communities (384 Operational Taxonomic Units, OTUs) with different taxonomic
      affiliations and ecological functions. The observed fungal communities primarily
      belonged to three phyla: Ascomycota, Basidiomycota and Chytridiomycota. Perceived
      dynamics in the composition of living fungal communities were significantly
      shaped by the concentration of ammonium in the moderately agriculturally impacted
      aquifer system. Apart from fungal saprotrophs, we also detected living plant and
      animal pathogens for the first time in this aquifer system. This work also
      demonstrates that the RNA-based high throughput pair-end illumina sequencing
      method can be used in future for water quality monitoring in terms of living
      fungal load and subsequent risk assessments. In general, this study contributes
      towards the growing knowledge of aquatic fungi in terrestrial subsurface
      biogeosphere.

PMID- 30118977
TI  - Women's experiences of exercising informed choices as expressed through their
      sense of self and relationships with others in Ireland: A participatory action
      research study.
AB  - OBJECTIVE: To explore women's experiences of the concept of informed choice
      during pregnancy and childbirth. METHODS: A three-phase action research approach.
      In the second phase of the study (reported in this paper), 15 women were
      interviewed to establish their experiences of informed choice. SETTING: Dublin,
      Ireland in a large maternity hospital. FINDINGS: We found that multiple factors
      influence how women experience informed choice including; their sense of self and
      the quality of their relationships with maternity care professionals. Women's
      experiences as expressed through their sense of self reveal that informed choice,
      is not only defined by but contingent on the quality of women's relationships
      with their caregiver and their ability to engage in a process of shared decision
      making with them. KEY CONCLUSIONS: Informed choice is experienced as a relational
      construct women's relationships with maternity care professionals can influence
      their perceptions of their sense of self following childbirth. Supportive
      relationships are key to supporting the concept of informed choice.

PMID- 30118978
TI  - Acute skeletal muscle wasting and relation to physical function in patients
      requiring extracorporeal membrane oxygenation (ECMO).
AB  - PURPOSE: Muscle weakness is common in patients requiring extracorporeal membrane
      oxygenation (ECMO), but early identification is challenging. This study aimed to
      1) quantify the change in quadriceps size and quality (echogenicity) from
      baseline to day 10 using ultrasound in patients requiring ECMO, 2) determine the
      relationship between ultrasound measures, muscle strength and highest mobility
      level. MATERIALS AND METHODS: Prospective cohort study involving ultrasound
      measurement of quadriceps at baseline, days 10 and 20. Muscle strength and
      highest mobility level were assessed at days 10 and 20 using the Medical Research
      Council sum-score (MRC), hand-held dynamometry (HHD) and the ICU mobility scale
      (IMS). RESULTS: 25 patients (age 49 +/- 14 years, 44% male) received ECMO. There
      was a significant reduction (-19%, p < .001) in rectus femoris cross-sectional
      area by day 10. Echogenicity did not change over time. There was a negative
      correlation between echogenicity and MRC at day 10 (r = -0.66) and HHD at day 20
      (r = -0.81). At day 20, there was a moderate correlation between total muscle
      thickness and IMS (rho = 0.59) and MRC (rho = 0.56). CONCLUSIONS: In patients
      requiring ECMO there was marked wasting of the quadriceps over the first 10 days.
      Ultrasound measures were related to muscle strength and highest mobility level.

PMID- 30118980
TI  - Metabolic glycan labeling and chemoselective functionalization of native
      biomaterials.
AB  - Decellularized native extracellular matrix (ECM) biomaterials are widely used in
      tissue engineering and have reached clinical application as biomesh implants. To
      enhance their regenerative properties and postimplantation performance, ECM
      biomaterials could be functionalized via immobilization of bioactive molecules.
      To facilitate ECM functionalization, we developed a metabolic glycan labeling
      approach using physiologic pathways to covalently incorporate click-reactive
      azide ligands into the native ECM of a wide variety of rodent tissues and organs
      in vivo, and into the ECM of isolated rodent and porcine lungs cultured ex vivo.
      The incorporated azides within the ECM were preserved after decellularization and
      served as chemoselective ligands for subsequent bioconjugation via click
      chemistry. As proof of principle, we generated alkyne-modified heparin,
      immobilized it onto azide-incorporated acellular lungs, and demonstrated its
      bioactivity by Antithrombin III immobilization and Factor Xa inhibition. The
      herein reported metabolic glycan labeling approach represents a novel platform
      technology for manufacturing click-reactive native ECM biomaterials, thereby
      enabling efficient and chemoselective functionalization of these materials to
      facilitate tissue regeneration and repair.

PMID- 30118979
TI  - Optoacoustic imaging identifies ovarian cancer using a microenvironment targeted
      theranostic wormhole mesoporous silica nanoparticle.
AB  - At the intersection of the newly emerging fields of optoacoustic imaging and
      theranostic nanomedicine, promising clinical progress can be made in dismal
      prognosis of ovarian cancer. An acidic pH targeted wormhole mesoporous silica
      nanoparticle (V7-RUBY) was developed to serve as a novel tumor specific
      theranostic nanoparticle detectable using multispectral optoacoustic tomographic
      (MSOT) imaging. We report the synthesis of a small, < 40 nm, biocompatible
      asymmetric wormhole pore mesoporous silica core particle that has both large
      loading capacity and favorable release kinetics combined with tumor-specific
      targeting and gatekeeping. V7-RUBY exploits the acidic tumor microenvironment for
      tumor-specific targeting and tumor-specific release. In vitro, treatment with V7
      RUBY containing either paclitaxel or carboplatin resulted in increased cell death
      at pH 6.6 in comparison to drug alone (p < 0.0001). In orthotopic ovarian
      xenograft mouse models, V7-RUBY containing IR780 was specifically detected within
      the tumor 7X and 4X higher than the liver and >10X higher than in the kidney
      using both multispectral optoacoustic tomography (MSOT) imaging with secondary
      confirmation using near infrared fluorescence imaging (p < 0.0004). The V7-RUBY
      system carrying a cargo of either contrast agent or an anti-neoplastic drug has
      the potential to become a theranostic nanoparticle which can improve both
      diagnosis and treatment of ovarian cancer.

PMID- 30118981
TI  - Structurally graduated collagen scaffolds applied to the ex vivo generation of
      platelets from human pluripotent stem cell-derived megakaryocytes: Enhancing
      production and purity.
AB  - Platelet transfusions are a key treatment option for a range of life threatening
      conditions including cancer, chemotherapy and surgery. Efficient ex vivo systems
      to generate donor independent platelets in clinically relevant numbers could
      provide a useful substitute. Large quantities of megakaryocytes (MKs) can be
      produced from human pluripotent stem cells, but in 2D culture the ratio of
      platelets harvested from MK cells has been limited and restricts production rate.
      The development of biomaterial cell supports that replicate vital hematopoietic
      micro-environment cues are one strategy that may increase in vitro platelet
      production rates from iPS derived Megakaryocyte cells. In this paper, we present
      the results obtained generating, simulating and using a novel structurally-graded
      collagen scaffold within a flow bioreactor system seeded with programmed stem
      cells. Theoretical analysis of porosity using micro-computed tomography analysis
      and synthetic micro-particle filtration provided a predictive tool to tailor cell
      distribution throughout the material. When used with MK programmed stem cells the
      graded scaffolds influenced cell location while maintaining the ability to
      continuously release metabolically active CD41 + CD42 + functional platelets.
      This scaffold design and novel fabrication technique offers a significant advance
      in understanding the influence of scaffold architectures on cell seeding,
      retention and platelet production.

PMID- 30118982
TI  - Aryl fluorosulfate analogues as potent antimicrobial agents: SAR, cytotoxicity
      and docking studies.
AB  - A series of aryl fluorosulfate analogues (1-37) were synthesized and tested for
      in vitro antibacterial and antifungal studies, and validated by docking studies.
      The compounds 9, 12, 14, 19, 25, 26, 35, 36 and 37 exhibited superior
      antibacterial potency against tested bacterial strains, while compounds 2, 4, 5,
      15, 35, 36 and 37 were found to have better antifungal activity against tested
      fungal strains, compared to standard antibiotic gentamicin and ketoconazole
      respectively. Among all the synthesized 37 analogs, compounds 25, 26, 35, 36 and
      37 displayed excellent anti-biofilm property against Staphylococcus aureus. The
      structure-activity relationship (SAR) revealed that the antimicrobial activity
      depends upon the presence of -OSO2F group and slender effect of different
      substituent's on the phenyl rings. The electron donating (OCH3) groups in analogs
      increase the antibacterial activity, and interestingly the electron withdrawing
      (Cl, NO2, F and Br) groups increase the antifungal activity (except compound 35,
      36 and 37). The mechanism of potent compounds showed membrane damage on bacteria
      confirmed by SEM. Compounds 35, 36 and 37 exhibited highest glide g-scores in
      molecular docking studies and validated the biocidal property.

PMID- 30118983
TI  - Novel thymol bearing oxypropanolamine derivatives as potent some metabolic enzyme
      inhibitors - Their antidiabetic, anticholinergic and antibacterial potentials.
AB  - A series of classical and newly synthesized thymol bearing oxypropanolamine
      compounds were synthesized and characterized. Their in vitro antibacterial
      activity on A. baumannii, P. aeruginosa, E. coli and S. aureus strains were
      investigated with agar well diffusion method. The results were compared with
      commercially available drug active compounds. As well as 3a, 3b and 3c have the
      most significant antibacterial effect among all the tested compounds;
      approximately all of them have more antibacterial activity than the reference
      drugs. These novel thymol bearing oxypropanolamine derivatives were effective
      inhibitors of the alpha-glycosidase, cytosolic carbonic anhydrase I and II
      isoforms (hCA I and II), and acetylcholinesterase enzymes (AChE) with Ki values
      in the range of 463.85-851.05 uM for alpha-glycosidase, 1.11-17.34 uM for hCA I,
      2.97-17.83 uM for hCA II, and 13.58-31.45 uM for AChE, respectively.

PMID- 30118985
TI  - An eco-friendly catalytic system for multicomponent, one-pot synthesis of novel
      spiro-chromeno indoline-triones and their anti-prostate cancer potentials
      evaluated via alkaline phosphatase inhibition mechanism.
AB  - A green and efficient straightforward tactic for the one-pot regioselective
      synthesis of novel 10,10-dimethyl-9,10,11,11a-tetrahydro-6H-spiro[chromeno[4,3
      b]chromene-7,3'-indoline]-2',6,8 (7aH) -triones (4a-n) in one-pot modus has been
      established using eco-friendly p-toluenesulphonic acid as catalyst. Among the
      solvents that were used for synthesis, 4a-n were suitably synthesized with
      maximum yield (90-98%) in water. We avoided column purification and the formed by
      product in the process is environmental-friendly. Hence, this reaction may
      consider as an astonishing piece work in this study, why because, the reaction
      mechanism that depends on the nature of the group attached to the isatin ring
      nitrogen atom. The main advantage of this protocol includes short reaction time,
      good yield, easy to work-up, practical simplicity, high regioselectivity and
      reduced pollutant, cost and avoids tedious purification. These pharmaceutically
      important compounds (4a-n) were recognized for their alkaline phosphatase
      inhibition and prostate cancer medication capabilities. The selective activity
      relation between alkaline phosphatase and prostate cancer was unveiled through
      the interaction of 4a-n to Human alkaline phosphatase (PDB ID: 1EW2).

PMID- 30118984
TI  - Polyamine derivatives from the bee pollen of Quercus mongolica with tyrosinase
      inhibitory activity.
AB  - Eighteen constituents, including nine new compounds, were isolated from the bee
      pollen of Quercus mongolica. The structures of the new compounds were established
      on the basis of combined spectroscopic analysis. Structurally, the nine new
      compounds are polyamine derivatives with phenolic moieties which were assigned as
      one putrescine derivative, mogolicine A (2), seven spermidine derivatives,
      mongolidines A-G (3-5, 8, 12, 14, 17) and one spermine derivative, mogoline A
      (18). Evaluation of the biological activity of isolated compounds revealed that
      the polyamine derivatives with coumaroyl and caffeoyl moieties showed tyrosinase
      inhibition with IC50 values of 19.5-85.8 MUM; however, the addition of a methoxy
      group to phenolic derivatives reduced the inhibitory activity.

PMID- 30118986
TI  - Synthesis, biological activity and structure activity relationship studies of
      novel conazole analogues via conventional, microwave and ultrasound mediated
      techniques.
AB  - 1,2,4-Triazole derivatives containing a piperazine nucleus (4a-d and 10) were
      prepared starting from 1-(2-methoxyphenyl)piperazine or ethyl 4-(4-amino-2
      fluorophenyl)piperazine-1-carboxylate via several steps. The synthesis of fifteen
      compounds (7a-l and 13a-c), which can be considered as new analogues of azole
      class antifungals was performed starting from 1,2,4-triazoles (4a-d and 10) via
      three steps containing the condensation with 2-bromo-1-(4-chlorophenyl)ethanone,
      reduction of carbonyl group to alcohol and alkylation of OH group, respectively.
      All the reactions were examined under conventional, ultrasound and microwave
      irradiation conditions as green chemistry techniques, and optimum conditions were
      defined. The newly synthesized compounds were screened for their biological
      potentials including antimicrobial, antioxidant, antiurease and anti alpha
      glucosidase activities and promising results were obtained. The enzyme inhibitory
      potentials of these compounds were further validated through molecular docking.

PMID- 30118987
TI  - DNA-binding, enzyme inhibition, and photochemical properties of chalcone
      containing metallophthalocyanine compounds.
AB  - In this study, two novel phthalocyanine complexes were synthesized using their
      corresponding metal salts and 4-(4-(3-(2,4,5
      trimethoxyphenyl)acryloyl)phenoxy)phthalo-nitrile as chalcone ligand (4), which
      was prepared from the reaction of 4-nitrophthalonitrile with 4-hydroxyphenyl-3
      (2,4,5-trimethoxyphenyl)prop-2-en-1-one (3). These metallophthalocyanines showed
      good solubility in organic solvents such as CDCl3, DCM, THF, DMF, and DMSO. The
      novel phthalocyanine compounds 4a (Pc-Zn) and 4b (Pc-Co) were characterized using
      their UV-vis, FT-IR, 1H NMR, 13C NMR, and MALDI-TOF mass spectra and elemental
      analysis. Then the DNA-binding and xanthine oxidase and carbonic anhydrase-I
      inhibition properties of compounds 4a and 4b were investigated. Photochemical
      properties (such as singlet oxygen generation and photodegradation) of this novel
      chalcone phthalocyanine (4a) were determined in dimethyl sulfoxide (DMSO).

PMID- 30118988
TI  - Synthesis and biological evaluation of N-aryl-2-phenyl-hydrazinecarbothioamides:
      Experimental and theoretical analysis on tyrosinase inhibition and interaction
      with HSA.
AB  - A series of N-aryl-2-phenyl-hydrazinecarbothioamides have been investigated as
      possible inhibitors of tyrosinase, an enzyme involved in the development of
      melanomas. The hydrazinecarbothioamides 1-6 were synthesized from the reaction
      between phenylhydrazine and isothiocyanates, for which three different methods
      have been employed, namely stirring at room temperature, by microwave irradiation
      or by mechanochemical grinding. Quantitative yields were obtained for the later
      technique. Compound 4 showed the best value for tyrosinase inhibition (IC50 =
      22.6 uM), which occurs through an uncompetitive mechanism. Molecular docking
      results suggested that 4 can interact via T-stacking with the substrate L-DOPA
      and via hydrogen bonding and hydrophobic forces with the amino acid residues Ala
      79, His-243, Val-247, Phe-263, Val-282, and Glu-321. The interaction between
      human serum albumin (HSA) and compound 4 occurs through a ground state
      association and does not perturb the secondary structure of the albumin as well
      as the microenvironment around Tyr and Trp residues. The binding is spontaneous,
      moderate and occurs mainly in the Sudlow's site I. Molecular docking results
      suggested hydrogen bonding, hydrophobic and electrostatic interactions as the
      main binding forces between the compound 4 and the amino acid residues Lys-198,
      Trp-214, Glu-449, Leu-452, and Leu-480.

PMID- 30118989
TI  - Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole scaffold as
      insecticidal/acaricidal agents.
AB  - In continuation of our program aimed at the development of natural product-based
      pesticidal agents, a series of matrinic amide derivatives containing 1,3,4
      thiadiazole scaffold were prepared, and their insecticidal and acaricidal
      activities were evaluated against Mythimna separata and Tetranychus cinnabarinus.
      Some compounds exhibited potent insecticidal and acaricidal activities. It
      suggested that R1 as a nitro group and R2 as a fluorine atom, were important for
      the insecticidal activity; R1 as the electron-donating groups and R2 as the
      methyl group, were necessary for the acaricidal activity.

PMID- 30118990
TI  - Cytotoxic ent-Abietane-type diterpenoids from the roots of Euphorbia
      ebracteolata.
AB  - Euphoroids A-C (1-3), three new ent-abietane-type diterpenoids, together with ten
      known analogues (4-13) were obtained from the roots of Euphorbia ebracteolata.
      The structures of these compounds were determined by extensive spectroscopic data
      analysis, including UV, HRESIMS, 1D-, and 2D-NMR data. The inhibitory effects of
      compounds 1-13 on human cancer cells were determined using the MTT assay. The
      results revealed that new compounds 2 and 3 showed moderate cytotoxic activities
      against human cancer cell lines. Especially, compound 3 displayed selective
      cytotoxic effect agains cancer cell lines.

PMID- 30118991
TI  - Synthesis of 1H-1,2,3-triazole derivatives as new alpha-glucosidase inhibitors
      and their molecular docking studies.
AB  - Inhibition of alpha-glucosidase is an effective strategy for controlling the post
      prandial hyperglycemia in diabetic patients. For the identification of new
      inhibitors of this enzyme, a series of new (R)-1-(2-(4-bromo-2-methoxyphenoxy)
      propyl)-4-(4-(trifluoromethyl) phenyl)-1H-1,2,3-triazole derivatives were
      synthesized (8a-d and 10a-e). The structures were confirmed by NMR, mass
      spectrometry and, in case of compound 8a, by single crystal X-ray
      crystallography. The alpha-glucosidase inhibitory activities were investigated in
      vitro. Most derivatives exhibited significant inhibitory activity against alpha
      glucosidase enzyme. Their structure-activity relationship and molecular docking
      studies were performed to elucidate the active pharmacophore against this enzyme.
      Compound 10b was the most active analogue with IC50 value of 14.2 uM, while
      compound 6 was found to be the least active having 218.1 uM. A preliminary
      structure-activity relationship suggested that the presence of 1H-1,2,3-triazole
      ring in 1H-1,2,3-triazole derivatives is responsible for this activity and can be
      used as anti-diabetic drugs. The molecular docking studies of all active
      compounds were performed, in order to understand the mode of binding interaction
      and the energy of this class of compounds.

PMID- 30118992
TI  - Reliability of colposcopy during pregnancy.
AB  - OBJECTIVE: To investigate the reliability of colposcopy during pregnancy and to
      evaluate the concordance between colposcopic patterns and histopathological
      findings in these women. STUDY DESIGN: Multicenter observational study of women
      diagnosed with an abnormal cervical cytology, who subsequently underwent a
      colposcopic evaluation with cervical biopsy during pregnancy. The "colpo
      histopathological concordance? was evaluated. The "colposcopic overestimation and
      underestimation? were evaluated as well. RESULTS: 69 women, fulfilling the study
      inclusion/exclusion criteria, constituted the study cohort. Among them, on
      colposcopic examination, 14 women (20.3%) showed "grade I abnormal colposcopic
      findings?, 52 (75.4%) showed "grade II abnormal colposcopic findings? and the
      remaining 3 women (4.3%) had a "suspicious for invasion? colposcopy. The
      histopathological diagnosis showed 2 negative biopsies, 12 (17.4%) cases of CIN1,
      50 (72.5%) cases of CIN2 and 5 (7.2%) cases of invasive cervical cancer. We found
      a colposcopic overestimation in 10 cases (14.5%), underestimation in 12 cases
      (17.4%), and a concordance in 47 cases (68.1%). A better reliability of
      colposcopy in women in the firsts two trimesters and in particular in women <=20
      weeks pregnant was found (Cohen's weighted kappa: 0.65). CONCLUSIONS: When
      performed by gynecologists with expertise, colposcopy is a reliable diagnostic
      tool, even during pregnancy. Whenever possible, a colposcopic evaluation during
      the first half of pregnancy is preferable.

PMID- 30118993
TI  - Psychosocial perspective and suicidal behaviors correlated with adolescent male
      smoking and illicit drug use.
AB  - OBJECTIVES: To assess the prevalence of smoking and drug use among adolescent
      boys, and to examine adolescents' psychosocial factors, and suicidal behaviors
      associated with adolescents' substance use. METHODS: The Kuwait Global School
      Based Student Health Survey employed a two-stage cluster sample design targeting
      a representative sample of adolescents. This study focused on the participated
      1310 boys. Statistical analysis included Chi-square test, student t-test, and
      multivariate analysis. RESULTS: The mean age was 14.5 +/- 0.03 years. The
      reported prevalence of: smoking, ever drug use, and both smoking and drug use
      were 26.6% (95% CI:24.2-29.1%) and 7.4% (95% CI:6.1-9.0%) and 5.5% (95% CI:4.4
      6.9%) respectively. Logistic regression model analysis revealed that adolescents
      whose parents smoke, suffered from insomnia, were victims of bullying, and had
      negative social school environment, were more likely than others to be smokers,
      drug users or both. Addendum, suicidal ideation, and its combination with
      suicidal planning and/or suicidal attempt were significantly associated with
      smoking. The odds of these life-threatening behaviors increased when drug use was
      reported and augmented when both smoking and drug use were experienced.
      CONCLUSIONS: Prevalence of smoking and illicit drug use were high among
      adolescent boys. This study confirmed the association between adolescents'
      smoking and substance use with psychosocial context, and suicidal behaviors.
      Addressing these predictors would be crucial in the development of effective
      strategies targeting the prevention of smoking and substance use, which might
      consequently reduce suicidal behaviors among adolescents.

PMID- 30118994
TI  - Association between dysfunction of autonomic nervous system activity and
      mortality in schizophrenia.
AB  - BACKGROUND: Patients with schizophrenia have a higher mortality risk than the
      general population. Additionally, the autonomic nervous system (ANS) activity of
      patients with schizophrenia is lower and more dysfunctional than that of the
      general population. Nonetheless, the association between ANS dysfunction and
      mortality in schizophrenia is unclear. The aim of this study was to investigate
      the association between ANS activity and mortality in schizophrenia and to
      evaluate the predictive values of heart rate variability for long-term survival.
      METHODS: This study involves the 10-year follow-up of a sample population
      consisting of 59 Japanese inpatients with schizophrenia between 60 and 70 years
      of age from 2007 to 2016. The ANS activity of all patients was evaluated using
      heart rate variability in 2007. RESULTS: Fifty-three participants could be
      followed up because they stayed in the hospital during the follow-up period. Of
      these patients, 11 died during follow-up. Their mean age at death was 70.55 +/-
      3.45 years. The parasympathetic activity of nonsurvivors was significantly lower
      than that of survivors, and multiple logistic regression analysis showed a
      significant association between death and parasympathetic activity. CONCLUSION:
      We suggest that decreased parasympathetic activity could be associated with 10
      year all-cause mortality in older schizophrenic patients.

PMID- 30118996
TI  - Prevalence and correlates of HIV testing and HIV-positive status in the US:
      Results from the National Epidemiological Survey on Alcohol and Related
      Conditions III (NESARC-III).
AB  - We used the 2012-2013 National Epidemiologic Survey on Alcohol and Related
      Conditions III (NESARC-III), a nationally representative sample of US adults (n =
      34,653), to estimate the prevalence and correlates of HIV testing and HIV status.
      The diagnostic interview used was the Alcohol Use Disorder and Associated
      Disabilities Interview Schedule-DSM-5 Version. We found that in 2012-2013, the
      prevalence of a history of HIV testing was 53.0% among females and 47.0% among
      males. Among individuals tested, the prevalence of HIV was 1.06%, resulting in a
      known estimated prevalence of 0.54% in the full sample. In adjusted results,
      being non-white, aged 30-44, having college, being non-heterosexual, having
      history of unprotected sex or history of childhood sexual abuse and lower mental
      health-related quality of life increased the odds of having been tested, whereas
      being foreign-born, 45 years or older, family income >=$20,000, being unemployed
      or a student, living in a rural setting and older age at first sex lowered those
      odds. Among those tested, being 30-64, being non-heterosexual, having history of
      unprotected sex or having a sexually transmitted disease in the last year was
      associated with greater odds of being HIV+. Having some college decreased those
      odds. In the adjusted results all psychiatric disorders were associated with
      increased rates of HIV testing, but only a lifetime history of drug use disorder
      and antisocial personality disorders were associated with HIV status among those
      tested. Despite CDC recommendations, only about half of US adults have ever been
      tested for HIV, interfering with efforts to eradicate HIV infection.

PMID- 30118995
TI  - Moderators and mediators of a maternal depression treatment study: Impact of
      maternal trauma and parenting on child outcomes.
AB  - OBJECTIVE: Treatment of maternal depression with psychotherapy has been shown to
      confer indirect benefits to school-age offspring with psychiatric disorders. The
      current study sought to understand mechanisms by which improvement in depressed
      mothers, with and without histories of trauma and treated with psychotherapy,
      produce changes in children who struggle with psychiatric illnesses themselves.
      We hypothesized that maternal history of childhood trauma would moderate the
      relationship between maternal and child outcomes and that increased positive and
      decreased negative parenting behaviors would mediate the relationship between
      maternal and child outcomes. We also examined whether maternal history of trauma
      would moderate the mediational effects of parenting behaviors. METHODS:
      Participants were dyads (n = 62) of mothers with major depressive disorder and
      their children, ages 7-18, with at least one internalizing disorder. Mothers were
      treated with nine sessions of psychotherapy and children were treated openly in
      the community. Dyads were evaluated every three months over one year. RESULTS:
      Maternal improvement in depressive symptoms was associated, in a lagged fashion,
      with child improvement in functioning six months later. There was a significant
      interaction of time and change in maternal symptoms [F(1, 45) = 5.84, p = 0.02],
      where change in maternal depressive symptoms from baseline to six months was
      robustly associated with change in child functioning from baseline to 12 months
      (beta = 0.49, p = 0.0002). Maternal history of childhood sexual abuse moderated
      the association between change in maternal and child depressive symptoms [F(1,87)
      = 5.8, p = 0.02], and maternal history of physical neglect moderated the
      relationship between improvement in maternal depression and improvement in child
      functioning [F(1,36) = 4.34, p = 0.04], where significant associations between
      maternal and child outcomes were only found in mothers without histories of
      sexual abuse or physical neglect. Increase in positive parenting strategies
      (acceptance) by mothers mediated 6-month lagged associations between maternal and
      child outcomes, but reduction in negative parenting strategies (psychological
      control) did not. Maternal history of childhood emotional neglect moderated the
      mediational model, such that improved positive parenting did not explain lagged
      improvement in child depression among the subset of mothers with childhood
      histories of emotional neglect. CONCLUSIONS: In dyads comprised of depressed
      mothers and school-age children with internalizing disorders, children improved
      when mothers improved, but not among those whose mothers who had histories of
      sexual abuse or physical neglect. Increased use of positive parenting strategies
      among mothers accounted for lagged relationships between improvement in maternal
      depressive symptoms and improvement in child functioning. This pattern was not,
      however, observed among mothers with childhood histories of emotional neglect.
      Interventions that directly enhance positive parenting and more rapidly change
      these behaviors may hasten improvement in offspring. Offspring of depressed
      mothers with histories of early trauma are at high risk for poor outcomes, even
      when their mothers receive depression treatment.

PMID- 30118998
TI  - Telomeric Recombination Induced by DNA Damage Results in Telomere Extension and
      Length Heterogeneity.
AB  - About 15% of human cancers counteract telomere loss by alternative lengthening of
      telomeres (ALT), which is attributed to homologous recombination (HR)-mediated
      events. But how telomeric HR leads to length elongation is poorly understood.
      Here, we explore telomere clustering and telomeric HR induced by double-stranded
      breaks (DSBs). We show that telomere clustering could occur at G1 and S phase of
      cell cycle and that three types of telomeric HR occur based on the manner of
      telomeric DNA exchange: equivalent telomeric sister chromatin exchange (T-SCE),
      inequivalent T-SCE, and No-SCE. While inequivalent T-SCE increases telomere
      length heterogeneity with no net gain of telomere length, No-SCE, which is
      presumably induced by interchromatid HR and/or break-induced replication, results
      in telomere elongation. Accordingly, cells subjected to long-term telomeric DSBs
      display increased heterogeneity of length and longer telomeres. We also
      demonstrate that DSBs-induced telomere elongation is telomerase independent.
      Moreover, telomeric recombination induced by DSBs is associated with formation of
      ALT-associated PML body and C-circle. Thus, DNA damage triggers recombination
      mediated elongation, leading to the induction of multiple ALT phenotypes.

PMID- 30119000
TI  - Analytical aspects of sunitinib and its geometric isomerism towards therapeutic
      drug monitoring in clinical routine.
AB  - Sunitinib malate, an oral multi-targeted tyrosine kinase inhibitor approved for
      the treatment of metastatic renal cell carcinoma, gastrointestinal stromal tumor,
      and well-differentiated pancreatic neuroendocrine tumors, has been identified as
      a potential candidate for therapeutic drug monitoring approach. Nevertheless, the
      development of an analytical assay suitable for clinical application for the
      quantification of the plasma concentration of sunitinib and its active
      metabolite, N-desethyl sunitinib, is limited by its Z/E isomerization when
      exposed to light. Several LC-MS/MS methods already published require protection
      from light during all sample handling procedures to avoid the formation of E
      isomer, which makes them not suitable for clinical practice. In order to obtain a
      simple and fast procedure to reconvert the E-isomer, formed during sample
      collection and treatment without light protection, and, thus, to have only Z
      isomer peak to quantify, we studied the Z/E photodegradation with special
      attention to the condition allowing the reverse reaction in plasma matrix. After
      30 min of light exposure, the E-isomer maximum percentage of both the analytes
      was reached (44% of E-sunitinib and 20% of E-N-desethyl sunitinib; these
      percentages were calculated with respect to the sum of E + Z). Moreover, the
      formation of the E-isomer increased up to 20% after lowering the pH of the
      solution. Since the reverse reaction takes place when the pre-exposed solution is
      placed in dark, we followed the E to Z-isomer kinetics into the autosampler. The
      conversion rate was very slow when the autosampler was set at 4  degrees C (after
      4 h the mean percentages of E-isomer were 50% for sunitinib and 22% for N
      desethyl sunitinib). The reconversion rate was considerably accelerated with the
      increasing of the temperature: incubating the analytical solution in a heated
      water bath for 5 min at 70  degrees C we obtained the quantitative (99%)
      reconversion of the E- to the Z-isomer. No effect of concentration was observed,
      while the presence of acids inhibited the reconversion. Based on these results, a
      simple and fast procedure was setup to quantitatively reconvert the E-isomer
      formed during sample collection and processing without light protection into its
      Z-form thus leading to a single peak to quantify. The application of this
      additional step allows to develop a LC-MS/MS method suitable to clinical
      practice, due to its practicality and speed.

PMID- 30119001
TI  - Theoretical studies on the feasibility of the hybrid nanocomposites of graphene
      quantum dot and phenoxazine-based dyes as an efficient sensitizer for dye
      sensitized solar cells.
AB  - The feasibility of the hybrid nanocomposites of the graphene quantum dot (GQD)
      and the phenoxazine-based dyes as the efficient sensitizer of the dye-sensitized
      solar cell (DSSC) is investigated. Based on the first principles density
      functional theory (DFT), the geometrical structures of the separate GQDs, the
      phenoxazine-based dyes, and their hybridized nanocomposites are fully optimized.
      The energy stabilities of the obtained structures are confirmed by harmonic
      frequency analysis. The optical absorptions of the optimized structures are
      calculated with the time-dependent DFT (TDDFT). The feasibility of the
      nanocomposites as the sensitizer of DSSC is examined by the charge spatial
      separation, the molecular orbital energy levels of the nanocomposites and the I
      /I3- electrolyte, and the conduction band minimum of TiO2 electrode. The results
      demonstrate that three of the eight considered nanocomposites satisfy the
      requirement of DSSC. Among them, GQD4-POXB with large LHE, high Voc, and
      enhancement absorption becomes the most promising candidate as a feasible
      sensitizer. These findings are helpful for the design of the sensitizer of DSSC
      or the solar energy harvesting materials with the nanocomposites.

PMID- 30119002
TI  - Complete dispersion analysis of single crystal EDDt.
AB  - We present the first complete dispersion analysis of the organic ethylenediamine
      d-tartrate (EDDt) in single crystal form in the spectral range of 5000-100 cm-1.
      The obtained oscillator parameters were used to generate the polarized and the
      cross-polarized spectra of randomly oriented polycrystalline EDDt. The comparison
      of the generated with the experimental spectra confirms the value of obtained
      oscillator parameters and dielectric tensor function.

PMID- 30119003
TI  - A comparison between digital camera and spectrophotometer for sensitive and
      selective kinetic determination of brilliant green in wastewaters.
AB  - In this study, a simple and novel kinetic spectrophotometric method has been
      proposed for the sensitive and highly selective determination of Brilliant Green.
      The method is based on the interaction of Brilliant Green with Triton X-100 in
      micellar media at room temperature. As a result of this interaction, the peak
      wavelength (625 nm) is gradually shifted toward longer wavelength region (634 nm)
      and more intensive hyper chromic effect has been seen. As well as, variations in
      the red, blue and green (RGB) components of the images as a function of time were
      observed. The kinetic interaction of Brilliant Green with Triton X-100 was
      recorded, using UV-Vis Spectrophotometer-diode array detector and a digital
      camera. The fixed-time method was used for the construction of a calibration
      curves. Brilliant Green can be measured in the range of 1.0 to 12.0 mg L-1 and
      1.0 to 10.0 mg L-1with the detection limit of 0.047 mg L-1 and 0.037 mg L-1 using
      spectrophotometer and digital camera, respectively. The proposed method has been
      successfully used to determine Brilliant Green in some wastewaters such as
      textile dye effluent and goldfish farming water in the presence of some
      triphenylmethan dyes as the interferences.

PMID- 30118999
TI  - Apigenin Inhibits UVB-Induced Skin Carcinogenesis: The Role of Thrombospondin-1
      as an Anti-Inflammatory Factor.
AB  - We have previously demonstrated that apigenin promotes the expression of
      antiangiogenic protein thrombospondin-1 (TSP1) via a mechanism driven by mRNA
      binding protein HuR. Here, we generated a novel mouse model with whole-body THBS
      1 gene knockout on SKH-1 genetic background, which allows studies of UVB-induced
      acute skin damage and carcinogenesis and tests TSP1 involvement in apigenin's
      anticancer effects. Apigenin significantly inhibited UVB-induced carcinogenesis
      in the wild-type (WT) animals but not in TSP1 KO (TKO) mice, suggesting that TSP1
      is a critical component of apigenin's chemopreventive function in UVB-induced
      skin cancer. Importantly, TKO mice presented with the elevated cutaneous
      inflammation at baseline, which was manifested by increased inflammatory
      infiltrates (neutrophils and macrophages) and elevated levels of the two key
      inflammatory cytokines, IL-6 and IL-12. In agreement, maintaining normal TSP1
      expression in the UVB-irradiated skin of WT mice using topical apigenin
      application caused a marked decrease of circulating inflammatory cytokines.
      Finally, TKO mice showed an altered population dynamics of the bone marrow
      myeloid progenitor cells (CD11b+), with dramatic expansion of the population of
      neutrophil progenitors (Ly6ClowLy6Ghigh) compared to the WT control. Our results
      indicate that the cutaneous tumor suppressor TSP1 is a critical mediator of the
      in vivo anticancer effect of apigenin in skin, specifically of its anti
      inflammatory action.

PMID- 30119004
TI  - Efficient and visual monitoring of cerium (III) ions by green-fluorescent carbon
      dots and paper-based sensing.
AB  - An efficient strategy for the synthesis of excitation-independent carbon nanodots
      has been provided. This functional nano-scale particle has been assembled by
      using citric acid and urea as raw materials through a microwave irradiation
      process in the absence of further surface modifications. The achieved
      nanomaterial demonstrates intensive green emissions and can be dispersible in
      aqueous environment. In particular, cerium (III) ion is able to quench its
      fluorescence emission intensity selectively and an "on-off" change has been
      observed. A good linearity between the concentration range of 10-6-10-4 M has
      been realized and the detection limit is determined to be 0.7 MUM. More
      importantly, we report a color-evolution based paper sensor for effective
      monitoring of Ce3+ by incorporating fluorescent nanoprobe onto the cellulose
      paper substrate.

PMID- 30119005
TI  - Two-dimensional porous (Co, Ni)-based monometallic hydroxides and bimetallic
      layered double hydroxides thin sheets with honeycomb-like nanostructure as
      positive electrode for high-performance hybrid supercapacitors.
AB  - CoNi layered double hydroxides (LDH) and related monometallic hydroxides (Ni(OH)2
      and Co(OH)2) were synthesized by a facile, simple and inexpensive method under
      mild condition (50  degrees C). The resulting products displayed a unique
      honeycomb-like nanoflakes array assembled two-dimensional (2D) thin sheets
      structure. Among them, CoNi-LDH thin sheets delivered higher specific capacity
      (394.5 C g-1 at 1 A g-1) with superior cyclic performance (92.3% capacity
      retention over 10,000 cycles) than Co/Ni monometallic hydroxides owing to the
      synergistic effect of cobalt and nickel. Afterward, hybrid supercapacitors (HSC)
      devices were fabricated using the as-obtained products (CoNi-LDH, Co(OH)2 and
      Ni(OH)2 thin sheets) and activated carbon (AC) as the positive and negative
      electrode, respectively. The operating voltage of the devices can be extended to
      1.6 V. What's more, the assembled CoNi-LDH HSC device exhibited a maximum energy
      density of 20.38 Wh kg-1 at the power density of 800 W kg-1. Consequently, these
      outstanding electrochemical performances of the CoNi-LDH thin sheet endow it with
      great potential to be implemented in HSCs or other energy storage systems.

PMID- 30119006
TI  - Surface PEGylation and biological imaging of fluorescent Tb3+-doped layered
      double hydroxides through the photoinduced RAFT polymerization.
AB  - Tb3+-doped layered double hydroxides (LDHs) exhibit excellent optical
      characteristics, uniform size and uniform morphologies when synthesized through a
      hydrothermal method. However, due to their lack of functional groups and poor
      dispersibility, applications of these fluorescent Tb3+-doped LDHs have been
      largely impeded especially in the biomedical fields. In this work, a novel
      strategy was developed for the surface modification of these fluorescent Tb3+
      doped LDHs using photoinduced surface-initiated reversible addition-fragmentation
      chain transfer (RAFT) polymerization with hydrophilic poly(ethylene glycol)
      methacrylate (PEGMA) as the monomer. The final products were obtained via the
      metal free surface-initiated RAFT polymerization with light irradiation.
      Successful preparation of these fluorescent LDHs polymer composites (LDH-PEG) was
      confirmed by a number of analytical technologies, such as transmission electron
      microscopy, Fourier transformed infrared spectroscopy, X-ray photoelectron
      spectroscopy and thermogravimetric analysis. In addition, laser scanning confocal
      microscope was employed to examine the cell uptake behavior of the LDH-PEG
      composites and evaluate their potential for biomedical applications. We
      demonstrated that the hydrophilic monomer PEGMA could be facilely grafted on the
      surface of Tb3+-doped LDHs through metal free photoinduced surface-initiated RAFT
      polymerization. The resultant LDH-PEG composites displayed high water
      dispersibility, strong fluorescence, low cytotoxicity and a desirable cell uptake
      performance. These features of the LDH-PEG composites indicated their great
      potential for biomedical applications. More importantly, photoinduced RAFT
      polymerization has the advantages of a conventional controlled living radical
      polymerization, which could overcome drawbacks such as toxicity, the fluorescence
      quenching effects of metal catalysts and the complex synthesis of chain transfer
      agents. Therefore, this method could be an alternative tool for the surface
      modification of materials and fabrication of multifunctional fluorescent
      nanomaterials based polymer composites.

PMID- 30119007
TI  - Facile synthesis of ZnCo-ZIFs-derived ZnxCo3-xO4 hollow polyhedron for efficient
      oxygen evolution reduction.
AB  - The construction of highly active and stable non-noble metal electrocatalysts for
      oxygen evolution reaction (OER) is a crucial requirement for green energy
      utilization. Herein, we report a novel hybrid nanostructure of Zn/Co bimetallic
      oxide (ZnxCo3-xO4) hollow polyhedron through a pyrolysis-oxidation strategy
      derived from bimetallic Zn, Co-zeolitic imidazolate frameworks (ZnCo-ZIFs)
      rhombic polyhedral. Benefiting from the synergistic effects between highly active
      metal oxide and the unique polyhedron structure, the ZnxCo3-xO4 hollow polyhedron
      hybrid displayed outstanding electrocatalytic performances in alkaline media.
      When the ZnxCo3-xO4 polyhedron was employed as electrocatalysts for OER, a
      potential as low as 1.66 V (vs. RHE) was required to deliver the current density
      of 10 mA cm-2 in 1 M KOH, and ZnxCo3-xO4 still presented superior activity after
      continuously working for cyclic voltammetric scanning of 1000 cycles.

PMID- 30119008
TI  - Global estimation of exposure to fine particulate matter (PM2.5) from household
      air pollution.
AB  - BACKGROUND: Exposure to household air pollution (HAP) from cooking with dirty
      fuels is a leading health risk factor within Asia, Africa and Central/South
      America. The concentration of particulate matter of diameter <= 2.5 MUm (PM2.5)
      is an important metric to evaluate HAP risk, however epidemiological studies have
      demonstrated significant variation in HAP-PM2.5 concentrations at household,
      community and country levels. To quantify the global risk due to HAP exposure,
      novel estimation methods are needed, as financial and resource constraints render
      it difficult to monitor exposures in all relevant areas. METHODS: A Bayesian,
      hierarchical HAP-PM2.5 global exposure model was developed using kitchen and
      female HAP-PM2.5 exposure data available in peer-reviewed studies from an updated
      World Health Organization Global HAP database. Cooking environment
      characteristics were selected using leave-one-out cross validation to predict
      quantitative HAP-PM2.5 measurements from 44 studies. Twenty-four hour HAP-PM2.5
      kitchen concentrations and male, female and child exposures were estimated for
      106 countries in Asia, Africa and Latin America. RESULTS: A model incorporating
      fuel/stove type (traditional wood, improved biomass, coal, dung and
      gas/electric), urban/rural location, wet/dry season and socio-demographic index
      resulted in a Bayesian R2 of 0.57. Relative to rural kitchens using gas or
      electricity, the mean global 24-hour HAP-PM2.5 concentrations were 290 MUg/m3
      higher (range of regional averages: 110, 880) for traditional stoves, 150 MUg/m3
      higher (range of regional averages: 50, 290) for improved biomass stoves, 850
      MUg/m3 higher (range of regional averages: 310, 2600) for animal dung stoves, and
      220 MUg/m3 higher (range of regional averages: 80, 650) for coal stoves. The
      modeled global average female/kitchen exposure ratio was 0.40. Average modeled
      female exposures from cooking with traditional wood stoves were 160 MUg/m3 in
      rural households and 170 MUg/m3 in urban households. Average male and child rural
      area exposures from traditional wood stoves were 120 MUg/m3 and 140 MUg/m3,
      respectively; average urban area exposures were identical to average rural
      exposures among both sub-groups. CONCLUSIONS: A Bayesian modeling approach was
      used to generate unique HAP-PM2.5 kitchen concentrations and personal exposure
      estimates for all countries, including those with little to no available
      quantitative HAP-PM2.5 exposure data. The global exposure model incorporating
      type of fuel-stove combinations can add specificity and reduce exposure
      misclassification to enable an improved global HAP risk assessment.

PMID- 30119009
TI  - Paddy soil drainage influences residue carbon contribution to methane emissions.
AB  - Water drainage is an important mitigation option for reducing CH4 (methane)
      emissions from residue-amended paddy soils. Several studies have indicated a long
      term reduction in CH4 emissions, even after re-flooding, suggesting that the
      mechanism goes beyond creating temporary oxidized conditions in the soil. In this
      pot trial, the effects of different drainage patterns on straw-derived CH4 and
      CO2 (carbon dioxide) emissions were compared to identify the balance between
      straw-carbon CH4 and CO2 emissions influenced by soil aeration over different
      periods, including effects of drainage on emissions during re-flooding. The water
      treatments included were: continuous flooding [C] as the control and five
      drainage patterns (pre-planting drainage [P], early-season drainage [E],
      midseason drainage [M], pre-planting plus midseason drainage [PM], early-season
      plus-midseason drainage [EM]). An equal amount of 13C-enriched rice straw was
      applied to all treatments to identify straw-derived 13C-gas emissions from soil
      carbon derived emissions. The highest fluxes of CH4 and delta13C-CH4 were
      recorded from the control treatment in the first week after straw application.
      The CH4 flux and delta13C-CH4 were reduced the most (0.1-0.8 MUg CH4 g-1 soil day
      1 and -13 to -340/00) in the pre-planting and pre-planting plus midseason
      drainage treatments at day one after transplanting. Total and straw-derived CH4
      emissions were reduced by 69% and 78% in pre-planting drainage and 77% and 87% in
      pre-planting plus midseason drainage respectively, compared to control. The early
      season, midseason, pre-planting plus midseason and early-season-plus-midseason
      drainage treatments resulted in higher total and straw-derived CO2 emissions
      compared to the control and pre-planting drainage treatments. The pre-planting
      and pre-planting plus midseason drainage treatments lowered the global warming
      potential by 47-53%, and early-season and early-season-plus-midseason drainage
      treatments reduced it by 24-31% compared to control. By using labelled crop
      residues, this experiment demonstrates a direct link between early drainage and
      reduced CH4 emissions from incorporated crop residues, eventually leading to a
      reduction in total global warming potential. It is suggested that accelerated
      decomposition of the residues during early season drainage prolonged the
      reduction in CH4 emissions. Therefore, it is important to introduce the early
      drainage as an effective measure to mitigate CH4 emissions from crop residues.

PMID- 30119010
TI  - Compost humic acid-like isolates from composting process as bio-based surfactant:
      Properties and feasibility to solubilize hydrocarbon from crude oil contaminated
      soil.
AB  - Biodecomposition of organic solid waste during composting process produces
      compost humic acid-like (cHAL), which is classified as biobased surfactant. The
      present study aimed to characterize the properties of cHAL substance which was
      formed during the composting process of crude oil contaminated soil, in terms of
      surface tension decline (DeltaST) and emulsification activity (EA), and evaluate
      the ability to solubilize hydrocarbons. Crude oil contaminated soil from a public
      oilfield in Wonocolo Sub-district, Bojonegoro, Indonesia, was composted under
      aerobic condition with varied biodegradable waste (yard waste and rumen residue)
      in separate reactors. The cHAL compounds were isolated from composting products
      from yard waste (Y100), rumen residue (R100), control of contaminated soil
      (S100), and mixed of contaminated soil and biodegradable waste (S50YR50). The
      results showed that DeltaST of cHAL isolates were ranged from 6.65 to 21.50 mN/m.
      The EA of cHAL isolates were in the range of 7.35-38.01%. The cHAL isolates were
      capable to solubilize 99 to 10,710 MUg/g of hydrocarbons. The cHAL isolates from
      R100 and S50YR50 are potential as surface tension reducer and emulsifier for
      hydrocarbon with values of those isolates were close to 0.50% Tween 80
      characteristics, and the abilities to solubilize hydrocarbon were comparable to
      1.00% Tween 80. A composition of 50% crude oil contaminated soil and 50% of
      biodegradable waste (yard waste and rumen residue) is recommended for composting
      crude oil contaminated soil.

PMID- 30119011
TI  - Pyrrole: An insight into recent pharmacological advances with structure activity
      relationship.
AB  - Pyrrole is a heterocyclic ring template with multiple pharmacophores that
      provides a way for the generation of library of enormous lead molecules. Owing to
      its vast pharmacological profile, pyrrole and its analogues have drawn much
      attention of the researchers/chemists round the globe to be explored exhaustively
      for the benefit of mankind. This review focusses on recent advancements;
      pertaining to pyrrole scaffold, discussing various aspects of structure activity
      relationship and its bioactivities.

PMID- 30119012
TI  - The C-terminus of varicella-zoster virus glycoprotein M contains trafficking
      motifs that mediate skin virulence in the SCID-human model of VZV pathogenesis.
AB  - Knowledge about the function of varicella-zoster virus glycoprotein M is limited;
      the requirement of gM for skin and neural tropism are unknown. VZV gM contains
      two predicted YXXPhi trafficking motifs and a dileucine motif in the carboxyl
      terminus. We constructed a recombinant VZV with gM truncated from the first
      YXXPhi and five additional viruses with YXXPhi tyrosine substitutions, alone and
      in combination with dileucine substitution. All recombinant viruses grew to high
      titer but mutation of the membrane-proximal YXXPhi motif reduced plaque size in
      cultured cells and altered gM localization. C-terminus truncation had a
      pronounced effect on virion morphogenesis and plaque size, but not on overall
      replication kinetics in vitro. Mutation of gM trafficking motifs and truncation
      attenuated replication in human skin xenografts in vivo; gM truncation did not
      alter neurotropism. Our results demonstrate that the gM C-terminus is dispensable
      for virus replication in cultured cells but is important for skin pathogenesis.

PMID- 30119013
TI  - Dual regulation of L-selectin (CD62L) by HIV-1: Enhanced expression by Vpr in
      contrast with cell-surface down-modulation by Nef and Vpu.
AB  - The HIV-1 accessory protein Vpr displays various activities that can favor viral
      replication such as G2 cell cycle arrest. Vpr also modulates host gene
      expression, although this property is poorly characterized. Here, we investigated
      the effect of Vpr on L-selectin (CD62L), which crucially controls leukocytes
      circulation and generation of immune responses against pathogens. We report that
      Vpr up-regulates CD62L mRNA level when individually expressed in Jurkat T cells
      as well as during HIV-1 infection of primary CD4+ T cells. Vpr mutant analysis
      and use of inhibitors suggest that the effect of Vpr on CD62L occurs
      independently of G2 arrest but requires activation of the ATR kinase. Yet,
      induction of CD62L expression by Vpr is contrasted by down-regulation of CD62L
      protein by Nef that, together with Vpu, induces a net reduction of cell-surface
      CD62L on HIV-1-infected cells, which may impact viral spread and evasion of
      immune responses.

PMID- 30119015
TI  - LDL dinitrosyl iron complex acts as an iron donor in mouse macrophages.
AB  - [Fe(NO)2] - modified nanoparticles of low-density protein (DNICLDL) can serve as
      conveyors of iron in the form of stable complexes with ApoB100 protein. As
      reported recently, in human hepatoma cells DNICLDL significantly increased the
      total iron content, while showing low toxicity. In the present work, we focused
      on the effects of internalization of DNIC-modified lipoproteins in macrophages,
      with special regards to cytotoxicity. DNICLDL was administered to a model
      macrophage cell line, RAW 264.7. Administration of DNICLDL considerably increased
      total iron content. High increase of iron was accompanied by moderate toxicity.
      As shown by in vitro plasmid nicking assay, chelation of iron in the form of DNIC
      strongly reduced the iron-related reactive oxygen species (ROS) -induced DNA
      damage. In addition, DNICLDL, plausibly due to its NO-donating activity, did not
      induce inducible nitric oxide synthase (iNOS) expression, as opposed to other
      forms of low-density protein (LDL).

PMID- 30119014
TI  - Structural and catalytic properties of the peroxygenase P450 enzyme CYP152K6 from
      Bacillus methanolicus.
AB  - The CYP152 family of cytochrome P450 enzymes (P450s or CYPs) are bacterial
      peroxygenases that use hydrogen peroxide to drive hydroxylation and
      decarboxylation of fatty acid substrates. We have expressed and purified a novel
      CYP152 family member - CYP152K6 from the methylotroph Bacillus methanolicus MGA3.
      CYP152K6 was characterized using spectroscopic, analytical and structural
      methods. CYP152K6, like its peroxygenase counterpart P450SPalpha (CYP152B1) from
      Sphingomonas paucimobilis, does not undergo significant fatty acid-induced
      perturbation to the heme spectrum, with the exception of a minor Soret shift
      observed on binding dodecanoic acid. However, CYP152K6 purified from an E. coli
      expression system was crystallized and its structure was determined to 1.3 A with
      tetradecanoic acid bound. No lipids were present in conditions used for
      crystallogenesis, and thus CYP152K6 must form a complex by incorporating the
      fatty acid from E. coli cells. Turnover studies with dodecanoic acid revealed
      several products, with 2-hydroxydodecanoic acid as the major product and much
      smaller quantities of 3-hydroxydodecanoic acid. Secondary turnover products were
      undec-1-en-1-ol, 2-hydroxydodec-2-enoic acid and 2,3-dihydroxydodecanoic acid.
      This is the first report of a 2,3-hydroxylated fatty acid product made by a
      peroxygenase P450, with the dihydroxylated product formed by CYP152K6-catalyzed 3
      hydroxylation of 2-hydroxydodecanoic acid, but not by 2-hydroxylation of 3
      hydroxydodecanoic acid.

PMID- 30119016
TI  - Oxidant Generation Resulting from the Interaction of Copper with Menadione
      (Vitamin K3)-a Model for Metal-mediated Oxidant Generation in Living Systems.
AB  - The oxidation of hydroquinones is of interest both due to the generation of
      reactive oxygen species (ROS) and to the implications to trace metal redox state.
      Menadione (MNQ), a typical toxicant quinone used extensively for studying the
      mechanisms underlying oxidative stress, is known to be an effective source of
      exogenous ROS. In this study, the kinetics and mechanism of the oxidation of
      menadiol (MNH2Q, the reduced form of MNQ) in the absence and presence of copper
      (Cu) over the pH range 6.0-7.5 was examined. The autoxidation rate increased with
      increasing pH and concentration of O2 and also slightly increased with increasing
      concentration of MNH2Q and MNQ with Cu shown to play a significant role in
      catalysing the oxidation of MNH2Q. A kinetic model showed that the mono
      deprotonated menadiol, MNHQ-, accounted for the pH dependence of the autoxidation
      rate. In this proposed mechanism, both MNH2Q and MNHQ- species were oxidized
      quickly by Cu(II), generating menadione semiquinone (MNSQ*-) and superoxide (O2*
      ) and the reduced form of Cu, Cu(I). Oxygen not only facilitated the catalytic
      role of Cu(II) by rapidly regenerating Cu(II) but also effectively removed MSNQ*
      , generating the important chain-propagating species O2*-. The model demonstrated
      that Cu(I) was a significant sink of O2*- resulting in the generation of H2O2
      with subsequent generation of highly oxidative intermediates including Cu(III).
      These results provide considerable insight into the clinical significance of the
      biological activation and detoxification of MNQ with the kinetic model developed
      of use in identifying key processes in the generation of harmful oxidants in
      living systems.

PMID- 30119017
TI  - High efficiency and rapid degradation of bisphenol A by the synergy between
      adsorption and oxidization on the MnO2@nano hollow carbon sphere.
AB  - In this research, a novel efficiency MnO2@Nano hollow carbon sphere (MnO2@NHCS)
      nanocomposite was prepared by one-pot hydrothermal reaction with KMnO4 solution.
      The adsorption and oxidization performance of MnO2@NHCS were assessed by
      degradation of bisphenol A (BPA) at different conditions. The effect of dosage of
      MnO2@NHCS, pH, initial concentration of BPA, temperature and humic acid were
      investigated systematically. Moreover, the characterizations of MnO2@NHCS were
      measured by a series of techniques, such as XRD, FESEM, HRTEM, TGA and XPS.
      Notably, hollow structure of nano carbon sphere was still retained with uniform
      MnO2 nanosheets covered. The results show that the removal rate of BPA was 95.3%
      within 10 min and BPA can be almost decomposed in 30 min under the optimal
      conditions. Additionally, the MnO2@NHCS remained stable and had a high
      regeneration efficiency (more than 85%) after 3 cycles (360 min). The reaction
      intermediates/products of oxidation of BPA were analyzed and the possible
      degradation pathways of BPA were proposed. These research results demonstrate
      that the MnO2@NHCS is a fleet and efficient material for BPA degradation in
      aqueous environment.

PMID- 30119018
TI  - Fabrication of PCL/PVP Electrospun Fibers loaded with Trans-anethole for Bone
      Regeneration in vitro.
AB  - Trans-anethole (TA) is a phenolic phytocompound widely used in the food and
      health sector because of its diverse biological properties. However, its role in
      the promotion of bone formation is not known. With the enhanced bioavailability
      of TA, we aimed to determine its effect on osteogenesis; TA at different
      concentrations (5, 10, and 20 MUM) was loaded onto polycaprolactone
      (PCL)/polyvinylpyrrolidone (PVP) fibers by the electrospinning technique. The
      synthesized PCL/PVP + TA fibers were subjected to physiochemical and material
      characterization. The addition of TA did not have any effect on fiber thickness,
      swelling, protein adsorption, degradation, or biomineralization. The fibers were
      compatible with mouse mesenchymal stem cells (mMSCs). A sustained release of TA
      from the fibers promoted osteoblast differentiation at the cellular and molecular
      levels. Furthermore, the release of TA from fibers up-regulated the expression of
      Runx2, a bone transcription factor, and its co-activators, which are key
      molecules for osteoblast differentiation. Thus, these results provide insights
      into the bioavailability of TA in promoting in vitro osteoblast differentiation
      and the potential applications of TA in bone regeneration.

PMID- 30119019
TI  - Transformation of naproxen during the chlorination process: Products
      identification and quantum chemistry validation.
AB  - The by-products produced by pharmaceutically active compounds (PhACs) during
      chlorination are attracting wide concern. Thus, the transformation and toxicity
      of naproxen (NAP) during the chlorination process were assessed in this study.
      The transformation of NAP was found to follow pseudo-first-order kinetics, and
      the first-order rate constant was improved by increasing the NaOCl dose. High
      resolution mass spectrometry (HRMS) was successfully applied to identify 14
      chlorination products. This study represents the first elucidation and report of
      the exact structure of the primary chlorine substitution product ((2S)-2-(5
      chloro-6-methoxy-2-naphthyl)propionic acid) based on HRMS and 1H NMR. Chlorine
      will primarily substitute the hydrogen atom on the C7 position of the naphthalene
      ring to form the mono-chlorine substitution product, as further validated at the
      theoretical level by quantum chemical calculations. A series of HOCl-induced
      reactions, including substitution, demethylation, and dehydrogenation, led to the
      transformation of NAP during the chlorination process. ECOSAR program revealed
      that the potential aquatic toxicity of the transformation products is
      significantly higher than that of the parent NAP. Their introduction into the
      environment may still pose potential risks.

PMID- 30119020
TI  - Selection of performance reference compound (PRC) for passive sampling of
      pharmaceutical residues in an effluent dominated river.
AB  - A passive sampling device, a polar organic chemical integrative sampler (POCIS),
      was used to monitor 13 pharmaceuticals and 8 transformation products in upstream
      and downstream wastewater treatment plant effluent. A POCIS laboratory
      calibration study was performed to determine uptake behavior and the effect of
      water flow on the sampling rate. Most compounds showed a linear accumulation, and
      the sampling rate values ranged from 0.031 to 0.559 L/day. The developed POCIS
      samplers were used in field experiments in a wastewater-impacted river. Using the
      calculated sampling rates, the time-weighted average concentration values were
      measured by three different approaches: (1) laboratory calibration sampling rates
      (2) performance reference compound (PRC) correction sampling rates and (3) field
      calibration sampling rates. Nine deuterated compounds (acetaminophen-d3,
      antipyrine-d3, sulfamethoxazole-d4, carbamazepine-d10, diclofenac acid-d4,
      clofibric acid-d4, bezafibrate-d6, ibuprofen-d3 and naproxen-d3) were studied as
      PRCs. Antipyrine-d3 was successfully tested as a PRC for sulfamethoxazole,
      ibuprofen, 2-hydroxy ibuprofen, diclofenac acid, 4-hydroxydiclofenac acid,
      carbamazepin, carbamazepin 10,11-epoxide, sulfadiazine, 1-naphthol, antipyrine,
      naproxen and 4-chlorobenzoic acid. Finally, the POCIS was used to monitor target
      compounds in river water and measure their attenuation. For most compounds, the
      POCIS attenuation results were not significantly different from those of the spot
      samples, which demonstrated that a POCIS with a PRC correction can determine the
      attenuation of organic micropollutants in rivers.

PMID- 30119021
TI  - A pressurized liquid extraction approach followed by standard addition method and
      UPLC-MS/MS for a fast multiclass determination of antibiotics in a complex
      matrix.
AB  - In this work a fast analytical method for the determination of macrolides,
      tetracyclines and fluoroquinolones in a compost originating from a mixture of
      sewage sludge, palm waste and grass was developed by ultra-high performance
      liquid chromatography coupled to mass spectrometry (U-HPLC/MS). Antibiotics were
      extracted from compost by using the accelerated solvent extraction (ASE). The
      chromatographic separation was carried out on a T3 Cortecs C18 column using a
      mobile phase gradient mixture of water acidified with 1% of formic acid and
      acetonitrile. Recoveries of 24-30%, 53-93%, 33-57%, 69-135% and 100-171% were
      obtained for roxithromycin (ROX), chlortetracycline (CTC), oxytetracycline (OTC),
      enrofloxacin (ENR) and ciprofloxacin (CIP), respectively. As the most part of
      antibiotics showed significant matrix effect (ME), the method was validated using
      the standard addition method (SAM) to correct the observed ME. Instrumental
      variation, of LC/MS system, showed that 93.75% of the relative standard deviation
      (RSD %) are below 15%, although the organic load of extracts. This analytical
      method was applied to assess the fate of antibiotics during composting. Two
      composting experiments were conducted separately after spiking sludge at 2
      different concentrations levels. The resulting elimination rates were of 52-76,
      69-100, 100 and 24-50% for ROX, CTC, OTC and CIP, respectively. These results
      suggest that composting process contributes to the removal of residuals
      concentrations of macrolides and tetracyclines while the fluoroquinolones persist
      in the final compost product.

PMID- 30119022
TI  - Enhanced adsorption of arsenate and antimonate by calcined Mg/Al layered double
      hydroxide: Investigation of comparative adsorption mechanism by surface
      characterization.
AB  - This study aims to investigate adsorption mechanisms of As(V) and Sb(V) on
      calcined Mg/Al layered double hydroxide (LDH). The calcination process of Mg/Al
      LDH (CLDH) considerably enhanced the adsorption capacity of As(V) and Sb(V) via
      reconstruction and new formation of brandholzite-like compound, respectively. The
      maximum adsorption capacity for As(V) and Sb(V) by CLDH was 102.9 mg/g and 303.3
      mg/g, respectively. The regeneration efficiency of As(V) by 0.5 M NaOH with 5 M
      NaCl mixed solution reached 72.3% during five regeneration cycles, while Sb(V)
      regeneration gradually decreased to 32.0% at the fifth regeneration cycles due to
      the irreversible surface complexation mechanism. Extended X-ray absorption fine
      structure (EXAFS) data displayed that Al plays a dominant role in the adsorption
      of As(V) on CLDH through bidentate-binuclear inner-sphere complex. On the other
      hand, XRD and EXAFS data revealed that Sb(V) formed a brandholzite-like structure
      Mg[Sb(OH)6]2.6H2O which forms outer-sphere complex by the hydrogen bonding
      between hexagonal plates of magnesium and antimony hydroxide. Although the
      formation of brandholzite-like structure causes the partial transformation of
      original structure of Mg/Al LDH during reconstruction process with decreasing
      regeneration efficiency, it could be attributed to high binding affinity between
      Sb(V) and Mg/Al LDH.

PMID- 30119023
TI  - Simple and fast method for the measurement of legacy and novel brominated flame
      retardants in human serum.
AB  - Recent and reliable human biomonitoring data on brominated flame retardants
      (BFRs), either legacy or new BFRs, are still needed to assess human exposure. The
      aim of this work was therefore to develop and validate an accurate, fast and user
      friendly analytical strategy for the determination of 15 legacy and novel BFRs in
      human serum namely 8 polybrominated diphenylethers (BDE-28, -47, -99, -100, -153,
      -154, -183, and -209), 1 hexabromobiphenyl (PBB-153), and 6 novel BFRs
      (pentabromotoluene, hexabromobenzene, pentabromoethylbenzene, 2-ethylhexy-2,3,4,5
      tetrabromobenzoate, 1,2-bis(2,4,6-tribromophenoxy)ethane, and
      decabromodiphenylethane). This analytical procedure consisted in a simple liquid
      liquid extraction followed by elution on a PHREE cartridge avoiding further
      laborious purification steps. The final determination was performed by gas
      chromatography coupled to mass spectrometry in electron capture negative
      ionization mode (GC-ECNI-MS). The 15 m long RTX-1614 allowed the simultaneous
      measurement of the 15 BFRs including low and high brominated species within a
      single injection on a single column. Except for 2-ethylhexy-2,3,4,5
      tetrabromobenzoate (EHTBB) which showed very high response variations resulting
      in poor linearity, trueness and precision, and decabromodiphenylethane for which
      very low sensitivity was achieved, the 13 other BFRs passed the validation
      process with recoveries varying between 56 and 82%, and limits of quantification
      (LOQs) ranging from 2.5 to 6.0 pg/ml (34.5 pg/ml for BDE-209). Within the
      validated range of concentrations, the relative bias from the introduced levels
      were below 20% while the intra and inter precisions were maintained below 15%.
      The reliability of the technique was confirmed by successfully analyzing
      interlaboratory test materials (AMAP ring test for POPs in human serum).

PMID- 30119024
TI  - Characterization of PBDD/F emissions from simulated polystyrene insulation foam
      via lab-scale programmed thermal treatment testing.
AB  - Accidental fires and open combustion are regarded as major potential contributors
      to the environmental release of polybrominated dibenzo-p-dioxins and
      dibenzofurans (PBDD/Fs). The characterization of PBDD/Fs emitted from thermal
      treatment of simulated polystyrene (PS) foam is reported in this study. PS,
      hexabromocyclododecane (HBCDD) and metals (or metallic compounds) composed the
      test samples, which imitated real extruded (XPS) and expanded (EPS) polystyrene
      thermal insulation foams. Test samples were subjected to thermal treatments under
      different experimental conditions. This study shows that the temperature, metal
      (metallic compound) content, and type of atmosphere are the key factors in the
      formation of congeners and PBDD/Fs during thermal processes. The total yield of
      polybrominated dibenzofurans (PBDFs) was greater than that of the polybrominated
      dibenzo-p-dioxins (PBDDs) during the test, and 1,2,3,7,8-PeBDF and 2,3,7,8-TBDF
      were the predominant congeners emitted during the thermal treatment experiments.

PMID- 30119025
TI  - Facile synthesis of ZrO2 coated BiOCl0.5I0.5 for photocatalytic oxidation
      adsorption of As(III) under visible light irradiation.
AB  - ZrO2 modified BiOCl0.5I0.5 composites (ZBCI), synthesized via a facile
      precipitation method at room temperature, were utilized to photocatalytically
      oxidize and adsorb arsenite from water under visible light irradiation. The
      composites were well characterized by using various techniques. With visible
      light irradiation, 5 mg L-1 of As(III) could be completely removed by ZBCI (0.25
      g L-1) in 90 min. Particularly, we found that ZBCI composites not only could
      oxidize As(III) into As(V) with visible light irradiation, but also could
      effectively capture the generated As(V), leading to the negligible residual
      As(III) or As(V) in aqueous solutions after 90 min treatment. In the fabricated
      composites, ZrO2 acted as the main adsorption sites while BiOCl0.5I0.5 served as
      the primary photocatalysis center. Because of the heterostructure of ZBCI, e-
      generated by BiOCl0.5I0.5 would be transferred to ZrO2 and inhibited e--h+
      recombination rate, contributing to the improved photocatalytic efficiency. ZBCI
      could effectively remove As(III) over a broad range of pH from 3 to 11. Chloride
      and nitrate did not obviously affect the photocatalytic As(III) removal, while
      sulfate and phosphate yet reduced the capture of As(III). Moreover, ZBCI
      composites exhibited high photocatalytic As(III) removal efficiency during the
      fourth reused cycles. The facile synthesized ZBCI could be employed to capture
      and oxidize As(III) from water.

PMID- 30119026
TI  - Anammox bacteria exhibit capacity to withstand long-term starvation stress: A
      proteomic-based investigation of survival mechanisms.
AB  - Although anammox bacteria are commonly exposed to long-term starvation during
      transportation and preservation process, physiological changes in these organisms
      during long-term starvation are not well understood, nor are the molecular bases
      of their starvation survival strategies. To reveal survival mechanisms during
      long-term anaerobic and anoxic starvation (60 days at 20 +/- 1  degrees C),
      metaproteomic technology was utilized to identify differentially expressed
      proteins in Candidatus Kuenenia stuttgartiensis. Our results showed that
      Candidatus Kuenenia stuttgartiensis exhibits a capacity to withstand long-term
      starvation stress. Although activity decay rates of 0.0129 d-1 and 0.0049 d-1
      were observed for anammox sludge in anoxic and anaerobic starvation, the relative
      abundance of Candidatus Kuenenia stuttgartiensis, the shape of anammox granules,
      and the fraction of viable cells remained constant under both anaerobic and
      anoxic starvation conditions. Metaproteomics results illustrated that Candidatus
      Kuenenia stuttgartiensis maintained stable levels of most intracellular proteins,
      especially enzymes involved in principal metabolic pathways after 60-d of
      anaerobic or anoxic starvation, thereby allowing cells to regain metabolic
      activities once substrates became available. Induction of starvation proteins
      could be a survival strategy employed by Candidatus Kuenenia stuttgartiensis to
      resist long-term starvation stresses. During anaerobic starvation, 34 proteins
      were upregulated, five of which were associated with carbohydrate catabolism and
      oxidation of organic compounds, thereby increasing potential for utilization of
      endogenous carbon sources to produce energy. During anoxic starvation, only two
      proteins were upregulated, which may be attributed to insufficient energy for the
      synthesis of starvation-induced proteins.

PMID- 30119027
TI  - Magnetic particles modification of coconut shell-derived activated carbon and
      biochar for effective removal of phenol from water.
AB  - The separation and recovery of pollutant-loaded magnetic carbon materials from
      organic contaminated environment is recently concerned, but the change of
      sorption ability and mechanism of activated carbon and biochar caused by magnetic
      particles modification still need to be explored. Here, the magnetic modification
      of two coconut shell-, coal-derived activated carbon and one biochar, and its
      effect on the removal of phenol from water were investigated. Magnetic activated
      carbon (MAC) and magnetic biochar (MBC) were prepared by co-precipitation. The
      increase of mass magnetic susceptibilities and energy dispersive X-ray
      spectroscopy (EDX) analysis showed that magnetic particles were successfully
      coated on the surface of virgin carbonaceous materials (VCMs). Magnetic
      modification enhanced the surface area and pore volume of activated carbon, and
      preserved those structure properties of biochar. Magnetic activated carbon had
      lower adsorption rates (10.641 g mg-1.min-1) than virgin activated carbon (20.575
      g mg-1.min-1) while magnetic biochar exhibited higher adsorption rate (0.618 g mg
      1.min-1) compared with virgin biochar (0.040 g mg-1.min-1), which were related to
      mass transport process. Data from Langmuir model results suggested that maximum
      adsorption capacities of three carbon adsorbents were increased by magnetic
      modification. The enhanced removal of phenol after magnetizing process may
      attribute to the increase of specific surface area and pore volume. Among
      VCMs/MCCs, magnetic coconut shell-derived carbon material with 951.84 m2/g
      surface area exhibited the most organic contaminant sorption performance. This
      finding gives insight into the adsorption mechanism of magnetic AC/BC for phenol,
      and provides a guidance to choose the appropriate magnetic composites to remove
      the organic contaminant effectively.

PMID- 30119028
TI  - Quantitative responses of potential nitrification and denitrification rates to
      the size of microbial communities in rice paddy soils.
AB  - Nitrification and denitrification are important to nitrogen balance in
      agricultural ecosystems. However, the molecular drivers and limiting steps for
      these microbial processes in rice paddy soils are not well understood. Here, we
      assessed soil properties and abundances of functional genes affiliated with
      nitrification (amoA and nxrA), denitrification (nirS, nirK and nosZ), nitrate
      reduction (narG and napA) processes, and measured potential nitrification and
      denitrification rates (PNRs and PDRs) at 15 sites in Xiamen, China. The soil
      properties imposed indirect impacts on the potential rates by mediating the
      relative abundances of microbial communities. No significant relationships
      between the size of microbial communities and the potential rates were observed.
      Instead, we found the variables that best explained the variations in the PNRs
      and PDRs were AOB/nirS and (nirK + nirS)/nosZ, respectively. The PNRs were mainly
      limited by the relative strength of two steps, namely bacterial ammonium
      oxidation and nitrite into nitric oxide reduction, whereas the PDRs were mainly
      limited by the relative strength of the second and last denitrification steps.
      These results indicated that the dynamics of microbial communities based on the
      relative gene abundances are valuable in integrating fluctuations in soil
      physicochemical properties and are indictive of potential rates in paddy soils.
      Results of this study contribute to our quantitative understanding of the
      relative importance of soil physicochemical and biological factors in driving
      microbial potential in paddy soils.

PMID- 30119029
TI  - Behavioral responses and starvation survival of Daphnia magna exposed to
      fluoxetine and propranolol.
AB  - Fluoxetine and propranolol are neuroactive human pharmaceuticals that occur
      frequently as pollutants in surface waters. The potential effects of these
      pharmaceuticals on aquatic organisms have raised concern but many adverse effects
      are not well characterized for a broad range of concentrations and endpoints. In
      this study, 6 biological parameters in the freshwater Cladoceran Daphnia magna
      were compared for their responses to fluoxetine or propranolol exposure: mobility
      (dichotomous response), active swimming time, swimming distance, swimming
      velocity, swimming acceleration speed, and survival in the absence of food
      (starvation-survival). Changes in swimming behavior was quantified by video
      tracking followed by image analyses at six exposure concentrations between 100
      ng/L and 10 mg/L. Active swimming time and swimming distance were the most
      responsive parameters among the behavioral traits. Sublethal exposure
      concentrations resulted in nonmonotonic responses and behavior profiling
      suggested that fluoxetine and propranolol stimulated swimming activity at 1-10
      MUg/L whereas lower (0.1-1 MUg/L) and higher exposure concentrations (>100 MUg/L)
      inhibited swimming activity. The ability to survive in the absence of food when
      exposed to fluoxetine or propranolol resulted in EC50 and EC10 values that were
      lower than for swimming behavior (EC50 of 0.79-0.99 mg/L; EC10 of 1.4-2.9 MUg/L).
      Starvation-survival appeared to be a potentially simple and sensitive endpoint
      for adverse effects in D. magna at intermediate exposure concentrations.
      Nonmonotonic behavioral responses at low exposure concentrations and decreased
      ability to survive starvation should be considered in assessment of adverse
      effects of pharmaceuticals to freshwater invertebrates.

PMID- 30119030
TI  - 4-Bromodiphenyl ether delays pubertal Leydig cell development in rats.
AB  - Polybrominated diphenyl ethers are a class of brominated flame retardants that
      are potential endocrine disruptors. 4-Bromodiphenyl ether (BDE-3) is the most
      abundant photodegradation product of higher polybrominated diphenyl ethers.
      However, whether BDE-3 affects Leydig cell development during puberty is still
      unknown. The objective of this study was to explore effects of BDE-3 on the
      pubertal development of rat Leydig cells. Male Sprague Dawley rats (35 days of
      age) were gavaged daily with BDE-3 (0, 50, 100, and 200 mg/kg body weight/day)
      for 21 days. BDE-3 decreased serum testosterone levels (1.099 +/- 0.412 ng/ml at
      a dose of 200 mg/kg BDE-3 when compared to the control level (2.402 +/- 0.184
      ng/ml, mean +/- S.E.). BDE-3 decreased Leydig cell size and cytoplasmic size at a
      dose of 200 mg/kg, decreased Lhcgr, Star, Dhh, and Sox9 mRNA levels at >= 100
      mg/kg and Scarb1, Cyp11a1, Hsd17b3, and Fshr at 200 mg/kg. BED-3 also decreased
      the phosphorylation of AKT1, AKT2, ERK1/2, and AMPK at 100 or 200 mg/kg. BDE-3 in
      vitro induced ROS generation, inhibited androgen production, down-regulated
      Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, Srd5a1, and Akr1c14 expression in immature
      Leydig cells after 24-h treatment. In conclusion, the current study indicates
      that BDE-3 disrupts Leydig cell development via suppressing AKT, ERK1/2, and AMPK
      phosphorylation and inducing ROS generation.

PMID- 30119031
TI  - Electrochemical advanced oxidation processes (EAOPs) as alternative treatment
      techniques for carwash wastewater reclamation.
AB  - Electrochemical advanced oxidation processes such as electrooxidation (EO),
      electrooxidation with hydrogen peroxide generation (EO-H2O2) and electro-Fenton
      process (EF) have been investigated as alternative treatment techniques for
      complete removal of anionic surfactants and organic matters from real carwash
      wastewater. The electrochemical processes were performed with acidified real
      carwash wastewater using boron doped anode and carbon felt cathode. In all cases,
      the chemical oxygen demand (COD) removal efficiency was always increased with
      rise in applied current and complete organic matter decay was achieved at applied
      current of 500 mA or above after 6 h of electrolysis. Faster and higher COD decay
      was observed with EF compared to either EO or EO-H2O2 treatment, at all currents
      and electrolysis time. Besides, complete degradation of anionic surfactants - the
      major organic content of the wastewater could be achieved at all applied currents
      studied irrespective of the process used, indicating the efficacy of processes
      for total remediation of real carwash wastewater. The short-chain carboxylic
      acids formed as the final organic byproducts were identified and quantified by
      ion-exclusion chromatography. More so, lower energy consumption and higher
      current efficiency were achieved with EF compared to EO-H2O2. Electrochemical
      treatment was found to be a powerful technology for the complete abatement of
      organic matter in carwash wastewater for possible reuse.

PMID- 30119032
TI  - Polygalacic acid inhibits MMPs expression and osteoarthritis via Wnt/beta-catenin
      and MAPK signal pathways suppression.
AB  - Osteoarthritis (OA) is a chronic degenerative joint disease that has been shown
      to be closely related to the over expression of matrix metalloproteinases (MMPs).
      Polygalacic acid is a triterpene isolated from the root of Polygala tenuifolia
      Willd. In the present study, the anti-inflammatory effect of polygalacic acid in
      OA was investigated as well as its in vitro and in vivo mechanism. In vitro, rat
      chondrocytes were induced with interleukin-1beta (IL-1beta) and treated with
      different concentrations of polygalacic acid; real-time PCR and Western blotting
      were performed to evaluate the expressions of MMP-3, MMP-9, MMP-13, and COX-2. In
      addition, the MAPK and Wnt/beta-catenin signaling pathways were analyzed via
      Western blotting and immunofluorescence staining. In vivo, a rat OA model was
      treated with polygalacic acid. Gross morphological and histological assessments
      were performed to evaluate the resulting cartilage damage. Polygalacic acid
      significantly reduced the expression of MMPs and COX-2, which could be induced by
      IL-1beta in rat chondrocytes. Furthermore, polygalacic acid treatment prevented
      the degeneration of cartilage in the rat OA model. To investigate the underlying
      mechanism, we found that polygalacic acid suppressed both the IL-1beta-induced
      activation of Wnt/beta-catenin and the mitogen-activated protein kinase (MAPK)
      signal pathway in chondrocytes. These results suggest that polygalacic acid may
      have a therapeutic effect in OA treatment.

PMID- 30119033
TI  - TMEM9 mediates IL-6 and IL-1beta secretion and is modulated by the Wnt pathway.
AB  - Novel studies have shown that the Transmembrane protein 9 (TMEM9) gene is
      localized at 1q41 and encodes a protein consisting of 183 amino acids with an N
      terminus containing many important domains. As a novel human transmembrane
      protein, TMEM9 is highly conserved in species from Caenorhabditis elegans to
      humans and is widely expressed in many tissues and cells. Moreover, TMEM9 may
      play an important role in intracellular transport and the growth of hepatoma
      cells. However, evidence for the function of TMEM9 in inflammation is still
      limited. We studied the expression of TMEM9 and its effect on cytokine secretion
      in tumor necrosis factor-alpha (TNF-alpha)-induced LX-2 cells. We proved that
      overexpression of TMEM9 by transfection with pEGFP-C2-TMEM9 may increase the
      expression of IL-6 and IL-1beta in LX-2 cells. At the same time, knockdown of
      TMEM9 expression by transfection with a TMEM9-siRNA decreased IL-6 and IL-1beta
      secretion in LX-2 cells. Additionally, our results proved that overexpression of
      TMEM9 enhanced the protein expression levels of the canonical Wnt/beta-catenin
      accompanied by an upregulation of wnt2b, wnt3a and beta-catenin protein levels in
      LX-2 cells treated with TNF-alpha. These results indicate that TMEM9 plays a
      significant role in TNF-alpha-enhanced cytokines (IL-6 and IL-1beta) secretion in
      LX-2 cells and that the canonical Wnt/beta-catenin signaling pathway is involved
      in the induction of these cytokine expressions.

PMID- 30119034
TI  - Association of the 2D:4D digit ratio with body composition among the Polish
      children aged 6-13 years.
AB  - The 2D:4D digit ratio is formed as a result of genetic factors but also prenatal
      exposure to sex hormones. The higher index value the higher concentration of the
      prenatal oestrogen. It is commonly known that testosterone is a hormone connected
      with muscle mass growth and that oestrogen affects adipogenesis. The aim of this
      study was to find if the digit ratio can be an informative indicator of the fat
      mass and muscle mass and body proportions in prepubertal children. Material and
      methods The analysed cohort included 420 children (221 girls and 199 boys) aged 6
      13 years. Pearson's and Spearman's tests were conducted to assess whether 2D:4D
      was significantly correlated with the body composition measurements. Multiple
      regression models and stepwise forward regression were applied to select the most
      important independent variables affecting fat mass (%) and muscle mass (%) as
      well as the BMI and the WHR. Results The study shows that the digit ratio is
      negatively correlated with muscle mass (MM%) among girls (p < 0.05).There was no
      similar relationship in the group of boys. The regression models showed a
      significant role in determining the body composition and body proportions played
      by maternal factors such as: maternal level of education and weight gain during
      pregnancy. Conclusions The 2D:4D digit ratio seems to be an informative indicator
      of the muscle mass development since girls' early childhood. Moreover, maternal
      environment is also important in forming the offspring's body composition and
      proportions.

PMID- 30119035
TI  - Metabolomics changes in patients with PAPP-A2 deficiency in response to rhIGF1
      treatment.
AB  - OBJECTIVE: Mutations in the pregnancy-associated plasma protein A2 (PAPP-A2) gene
      have recently been shown to cause postnatal growth failure in two prepubertal
      patients from a non-consanguineous Spanish family due to the resulting decrease
      in IGF1 bioavailability. Although a specific pharmacological treatment of this
      entity is yet to be established, both children received progressive subcutaneous
      doses (40 to 120 MUg/kg) of rhIGF1 twice daily for 2 years. The improvements in
      growth, hyperinsulinemia and bone mineral density have been previously reported.
      The objective of this study was to analyze the changes in metabolism associated
      with these responses to rhIGF1 treatment. DESIGN: Herein we present a detailed
      characterization of the acute and long-term changes in the metabolic profiles of
      these two siblings with PAPP-A2 deficiency after the initial injections of rhIGF1
      and after two years of treatment. RESULTS: By using a GC-MS-based untargeted
      metabolomics approach, metabolic fingerprinting yielded the identification of 70
      serum metabolites including amino acids (46%), organic acids (21%) carbohydrates
      (16%), fatty acids (14%), and purine bases (3%). Free fatty acids (FFAs) and
      amino acids showed the largest changes in the compared metabolic profiles,
      suggesting that rhIGF1 treatment has the greatest effects on lipid and protein
      metabolic pathways in the PAPP-A2 deficient subjects. CONCLUSIONS: The
      administration of rhIGF1 resulted in changes related to crucial metabolic
      pathways, including lipid and protein metabolism, and this could be associated
      with the previously reported treatment-induced improvement in the mild basal
      hyperinsulinemia.

PMID- 30119036
TI  - Impacts of the combined exposure to seawater acidification and arsenic on the
      proteome of Crassostrea angulata and Crassostrea gigas.
AB  - Proteomic analysis was performed to compare the effects of Arsenic (As), seawater
      acidification (Low pH) and the combination of both stressors (Low pH + As) on
      Crassostrea angulata and Crassostrea gigas juveniles in the context of global
      environmental change. This study aimed to elucidate if two closely related
      Crassostrea species respond similarly to these environmental stressors,
      considering both single and combined exposures, to infer if the simultaneous
      exposure to both stressors induced a differentiated response. Identification of
      the most important differentially expressed proteins between conditions revealed
      marked differences in the response of each species towards single and combined
      exposures, evidencing species-related differences towards each experimental
      condition. Moreover, protein alterations observed in the combined exposure (Low
      pH + As) were substantially different from those observed in single exposures.
      Identified proteins and their putative biological functions revealed an array of
      modes of action in each condition. Among the most important, those involved in
      cellular structure (Actin, Atlastin, Severin, Gelsolin, Coronin) and
      extracellular matrix modulation (Ependymin, Tight junction ZO-1, Neprilysin) were
      strongly regulated, although in different exposure conditions and species. Data
      also revealed differences regarding metabolic modulation capacity (ATP beta,
      Enolase, Aconitate hydratase) and oxidative stress response (Aldehyde
      dehydrogenase, Lactoylglutathione, Retinal dehydrogenase) of each species, which
      also depended on single or combined exposures, illustrating a different response
      capacity of both oyster species to the presence of multiple stressors.
      Interestingly, alterations of piRNA abundance in C. angulata suggested genome
      reconfiguration in response to multiple stressors, likely an important mode of
      action related to adaptive evolution mechanisms previously unknown to oyster
      species, which requires further investigation. The present findings provide a
      deeper insight into the complexity of C. angulata and C. gigas responses to
      environmental stress at the proteome level, evidencing different capacities to
      endure abiotic changes, with relevance regarding the ecophysiological fitness of
      each species and competitive advantages in a changing environment.

PMID- 30119037
TI  - Strain behavior of malaligned cervical spine implanted with metal-on
      polyethylene, metal-on-metal, and elastomeric artificial disc prostheses - A
      finite element analysis.
AB  - BACKGROUND: Postoperative alterations in cervical spine curvature (i.e. loss of
      lordotic angle) are frequently observed following total disc replacement surgery.
      However, it remains unclear whether such changes in lordotic angle are due to
      preoperative spinal deformities and/or prostheses design limitations. The
      objective of the study is to investigate strain and segmental biomechanics of the
      malaligned cervical spine following total disc replacement. METHODS: Three disc
      prostheses were chosen, namely a metal-on-polyethylene, a metal-on-metal, and an
      elastomeric prosthesis, which feature different geometrical and material design
      characteristics. All discs were modelled and implanted into multi-segmental
      cervical spine finite element model (C3-C7) with normal, straight and kyphotic
      alignments. Comparative analyses were performed by using a hybrid protocol.
      FINDINGS: The results indicated that as the spine loses lordotic alignment, the
      prosthesis with elastomeric core tends to produce significantly larger flexion
      range of motion (difference up to 6.1 degrees ) than metal-on-polyethylene and
      metal-on-metal prostheses. In contrast, when the treated spine had normal
      lordotic alignment, the range of motion behaviors of different prostheses are
      rather similar (difference within 1.9 degrees ). Large localized strains up to
      84.8% were found with the elastomeric prosthesis, causing a collapsed anterior
      disc space under flexion loads. INTERPRETATION: Changes in cervical spinal
      alignments could significantly affect the surgical-level range of motion
      behaviors following disc arthroplasty; the in situ performance was largely
      dependent on the designs of the artificial disc devices in particular to the
      material properties.

PMID- 30119038
TI  - Building medical image classifiers with very limited data using segmentation
      networks.
AB  - Deep learning has shown promising results in medical image analysis, however, the
      lack of very large annotated datasets confines its full potential. Although
      transfer learning with ImageNet pre-trained classification models can alleviate
      the problem, constrained image sizes and model complexities can lead to
      unnecessary increase in computational cost and decrease in performance. As many
      common morphological features are usually shared by different classification
      tasks of an organ, it is greatly beneficial if we can extract such features to
      improve classification with limited samples. Therefore, inspired by the idea of
      curriculum learning, we propose a strategy for building medical image classifiers
      using features from segmentation networks. By using a segmentation network pre
      trained on similar data as the classification task, the machine can first learn
      the simpler shape and structural concepts before tackling the actual
      classification problem which usually involves more complicated concepts. Using
      our proposed framework on a 3D three-class brain tumor type classification
      problem, we achieved 82% accuracy on 191 testing samples with 91 training
      samples. When applying to a 2D nine-class cardiac semantic level classification
      problem, we achieved 86% accuracy on 263 testing samples with 108 training
      samples. Comparisons with ImageNet pre-trained classifiers and classifiers
      trained from scratch are presented.

PMID- 30119039
TI  - Optimisation of a modified submerged bed biofilm reactor for biological
      oleochemical wastewater treatment.
AB  - Oleochemicals industry effluence mainly contains a high chemical oxygen demand
      (COD) in a range of 6000-20,000 ppm. An effective biological wastewater treatment
      process must be carried out before wastewater is discharged into the environment.
      In this study, a submerged bed biofilm reactor (SBBR) was adapted to the
      biological oleochemical wastewater treatment plant observed in the present study.
      The effect of wastewater flow rate (100-300 mL/min), Cosmoball(r) percentage in
      the SBBR system (25-75%), and percentage of activated sludge (0-50%) were
      investigated in terms of COD reduction. The Box-Behnken design was used for
      response surface methodology (RSM) and to create a set of 18 experimental runs,
      which was needed for optimising the biological oleochemical wastewater treatment.
      A quadratic polynomial model with estimated coefficients was developed to
      describe COD reduction patterns. The analysis of variance (ANOVA) shows that the
      wastewater flow rate was the most effective factor in reducing COD, followed by
      activated sludge percentage and Cosmoball(r) carrier percentage. Under the
      optimum conditions (i.e., a wastewater flow rate of 103.25 mL/min a Cosmoball(r)
      carrier percentage of 71.94%, and an activated sludge percentage of 40.50%) a COD
      reduction of 98% was achieved. Thus, under optimum conditions, as suggested by
      the BBD, SBBR systems can be used as a viable means of biological wastewater
      treatment in the oleochemicals industry.

PMID- 30119040
TI  - Effect of immobilization on growth and organics removal of chlorella in
      fracturing flowback fluids treatment.
AB  - In this paper, fracturing flowback fluids were biologically treated by
      immobilized chlorella. The individual and interactive effects of three variables
      (sodium alginate concentration, CaCl2 concentration, and crosslinking time) on
      growth of immobilized algal were optimized by response surface methodology
      combined with Box-Behnken design. The results showed that the SA (sodium
      alginate) concentration most significantly affected algal density and treatment
      efficiency. The interaction between SA concentration and crosslinking time was
      weak, the interaction between CaCl2 concentration and crosslinking time was
      modest, while the interaction between SA concentration and CaCl2 concentration
      was significant. The immobilized chlorella performed the best when the SA
      concentration, CaCl2 concentration and crosslinking time were 2.42%, 2.69% and
      16.76 h, respectively, and the COD removal rate of fracturing flowback fluids was
      significantly higher than that of the free algal (34.70% vs. 8.96%), indicating
      immobilization could improve growth and organics removal of chlorellas for
      processing fracturing flowback fluids.

PMID- 30119041
TI  - Public perceptions of mountain lake fisheries management in national parks.
AB  - The legacy of fish stocking in mountain lake ecosystems has left behind a
      challenge for land managers around the globe. In the US and Canada, historically
      fishless mountain lakes have been stocked with trout for over a century. These
      non-native trout have cascading ecosystem effects, and can accumulate
      atmospherically deposited contaminants. While the negative impacts of stocking in
      these ecosystems have become increasingly apparent, wilderness fishing has
      garnered cultural value in the angling community. As a result, public lands
      managers are left with conflicting priorities. National park managers across the
      western US are actively trying to reconcile the cultural and ecological values of
      mountain lakes through the development of management plans for mountain lake
      fisheries. However, visitors' social perceptions, attitudes, and values regarding
      mountain lake fisheries management have remained unquantified, and thus largely
      left out of the decision-making process. Our study evaluated the recreation
      habits, values, and attitudes of national park visitors towards fish stocking and
      management of mountain lakes of two national parks in the Pacific Northwest. We
      found that most visitors favor fish removal using a conservation approach,
      whereby sensitive lakes are restored, while fish populations are maintained in
      lakes that are more resilient. An important consideration for managers is that
      many mountain lake anglers consume fish on an annual basis, thus we emphasize the
      use of outreach and education regarding the accumulation of contaminants in fish
      tissues. Our findings help elucidate the conflicting views of stakeholders, and
      we provide recommendations to inform management of mountain lakes fisheries in
      North America and abroad.

PMID- 30119042
TI  - Bioremediation and biomass production from the cultivation of probiotic
      Saccharomyces boulardii in parboiled rice effluent.
AB  - The parboilization of rice generates 2 L of effluent per kilogram of processed
      grain. Several methodologies have previously been tested with the aim of reducing
      the environmental impact of this effluent. The objective of this study was to
      evaluate the bioremediation of parboiled rice effluent supplemented with sucrose
      or residual glycerol from the biodiesel during the cultivation of the
      Saccharomyces boulardii probiotic. In the first stage of the experiment, cultures
      were grown in orbital shaker, and five media compositions were evaluated: 1)
      parboiled rice effluent; 2) effluent supplemented with 1% sucrose; 3) effluent
      supplemented with 3% sucrose; 4) effluent supplemented with 15 g.L-1 of biodiesel
      glycerol and 5) standard yeast culture medium (YM). The addition of 1% of sucrose
      generated the most promising results in terms of cell viability, removal of
      nitrogen, phosphorus and chemical oxygen demand (COD). From these results, four
      independent cultures were grown in a bioreactor using effluent +1% of sucrose as
      the medium. This assays generated a mean of 3.8 g.L-1 of biomass, 1.8 * 1011
      CFU.L-1, and removal of 74% of COD and 78% of phosphorus. Therefore, the
      cultivation of Saccharomyces boulardii in parboiled rice effluent supplemented
      with 1% sucrose may represent a viable method by which the environmental impact
      of this effluent can be reduced while simultaneously producing probiotic culture
      for use in animal production.

PMID- 30119043
TI  - Lysozyme as a flocculant-inducing agent improving the silica removal from aqueous
      solutions - A turbidimetric study.
AB  - In this paper, the lysozyme (LSZ) adsorption impact on the silica suspension
      stability was established. In other words, the stabilization/destabilization
      mechanism of the SiO2/LSZ system was explained based on the adsorption,
      electrokinetic and stability measurement results. Lysozyme adsorbs on the silica
      surface in the whole pH range. This process contributes to the changes in silica
      surface charge and zeta potential values. The lysozyme addition influences the
      system stability too. At pH 7.6 and 9, a large decrease in the silica suspension
      stability was found. It is connected with the neutralization of solid negative
      charge by the positively charged macromolecules. As a result, large aggregates
      can be formed, which is highly desirable in the silica removal procedure.

PMID- 30119044
TI  - Coupling heavy metal resistance and oxygen flexibility for bioremoval of copper
      ions by newly isolated Citrobacter freundii JPG1.
AB  - The potential for bioremoval of copper ions was investigated by a novel strain of
      bacterium Citrobacter freundii JPG1, which was newly isolated from gold mining
      tailing in China and grew either aerobically or anaerobically. The strain cross
      tolerated heavy metals of Ag+, Cd2+, Co2+, Cr6+, Cu2+ and Ni2+ and removed copper
      under both aerobic and anaerobic conditions with the stress of copper. Under
      aerobic conditions, the cells grew rapidly and exhibited higher biomass at low
      copper concentrations (<1 mmol L-1), while the growth of cells was almost
      completely inhibited at high copper concentrations (2 mmol L-1). However, the
      cell growths were less affected by copper under anaerobic conditions. Similarly,
      the copper-removal efficiency was affected by oxygen and the capability of copper
      removal by anaerobic cells was significantly higher than that of aerobic cells (P
      < 0.05). The quantitative measurement of extracellular biosorption and
      intercellular bioaccumulation of copper indicated that biosorption efficiencies
      for aerobic cells (37%) and anaerobic cells (38%) were similar but the
      bioaccumulation by anaerobic cells was almost ten-fold higher than that by
      aerobic cells, indicating bioaccumulation contributed most in copper reduction
      under anaerobic conditions. Overall, the results suggested the facultative strain
      C. freundii JPG1 had great potential in the treatment of copper-laden industrial
      wastewater under both aerobic and anaerobic conditions.

PMID- 30119045
TI  - Assessing organizations performance on the basis of GHRM practices using BWM and
      Fuzzy TOPSIS.
AB  - Over the past few years, the need for sustainable environmental management has
      increased rapidly and green management has emerged as an important tool for the
      same. The role of Green Human Resource Management (GHRM) practices in
      environmental management and green management is widely known but still lesser
      discussed in academic literature. Thus, realizing the importance of GHRM in
      environmental management by organizations, this study attempts to identify the
      important practices of GHRM and evaluate the performance of manufacturing
      organizations using GHRM practices. A three-phase methodology is used for the
      same. The first phase involves identification of GHRM practices in manufacturing
      organizations through literature review and expert opinion. The second phase
      involves ranking of GHRM practices using Best Worst Method (BWM) and third phase
      methodology involves evaluating manufacturing organizations on the basis of GHRM
      practices using Fuzzy Technique for Order Preference by Similarity to Ideal
      Solution (TOPSIS). This research can help managers to identify important
      practices of GHRM for their organization. This study also provides a framework
      for managers to evaluate their organization's performance on the basis of GHRM
      practices.

PMID- 30119046
TI  - Combining high performance fertiliser with surfactants to reduce the reverse
      solute flux in the fertiliser drawn forward osmosis process.
AB  - Solutions to mitigate the reverse diffusion of solutes are critical to the
      successful commercialisation of the fertiliser drawn forward osmosis process. In
      this study, we proposed to combine a high performance fertiliser (i.e., ammonium
      sulfate or SOA) with surfactants as additives as an approach to reduce the
      reverse diffusion of ammonium ions. Results showed that combining SOA with both
      anionic and non-ionic surfactants can help in reducing the reverse salt diffusion
      by up to 67%. We hypothesised that, hydrophobic interactions between the
      surfactant tails and the membrane surface likely constricted membrane pores
      resulting in increased rejection of ions with large hydrated radii such as SO42-.
      By electroneutrality, the rejection of the counter ions (i.e., NH4+) also
      therefore subsequently improved. Anionic surfactant was found to further decrease
      the reverse salt diffusion due to electrostatic repulsions between the surfactant
      negatively-charged heads and SO42-. However, when the feed solution contains
      cations with small hydrated radii (e.g., Na+); it was found that NH4+ ions can be
      substituted in the DS to maintain its electroneutrality and thus the diffusion of
      NH4+ to the feed solution was increased.

PMID- 30119047
TI  - Visual letter similarity effects during sentence reading: Evidence from the
      boundary technique.
AB  - The study of how the cognitive system encodes letter identities from the visual
      input has received much attention in models of visual word recognition but it has
      typically been overlooked in models of eye movement control in reading. Here we
      examined how visual letter similarity affects early word processing during
      reading using Rayner's (1975) boundary change technique in which the parafoveal
      preview of the target word was either identical (e.g., frito-frito [fried]) or a
      one-letter-different nonword (e.g., frjto-frito vs. frgto-frito). Critically, the
      substituted letter in the nonword was visually similar (based on letter
      confusability norms) or visually dissimilar. Results showed shorter viewing times
      on the target word when the parafoveal preview was visually similar than when it
      was visually dissimilar. Thus, visual letter similarity modulates the integration
      of parafoveal and foveal information during sentence reading. Future
      implementations of models of eye movement control in reading should incorporate a
      more developed orthographic-lexical module to capture these effects.

PMID- 30119048
TI  - The perceptual enhancement by spatial attention is impaired during the
      attentional blink.
AB  - A salient, but task-irrelevant stimulus has long been known to capture attention
      in an automatic, involuntary manner. However, the automaticity of involuntary
      attention has recently been challenged. While some studies showed that the effect
      of involuntary attention depended on top-down attentional resources, other
      studies did not. To reconcile this conflict, we suggest to consider that
      attentional effect is not homogenous. Specifically, we hypothesized that the
      dependence of involuntary attention on top-down attention interacts with the
      presence/absence of the target location uncertainty and distractor interference.
      Consistent with this hypothesis, we found that when the attentional resources
      were depleted, the involuntary attention did not affect the perception of a
      single target stimulus (Experiment 1). However, when the target was accompanied
      by multiple distractors, evoking uncertainty regarding the target location, the
      involuntary attentional effect was observed, regardless of the availability of
      attentional resource (Experiment 2). This was so, even when the target location
      was always marked by a response cue, minimizing the target location uncertainty
      (Experiment 3). These findings provide a reconciliation for the theoretical
      debate regarding the dependence of involuntary attention on top-down attention
      and clarifies how perception is modulated by involuntary attention.

PMID- 30119049
TI  - Robust intentional binding for causally-linked sequences of naturalistic events
      but not for abstract event sequences.
AB  - Past studies have shown that when a voluntary action produces a sensory effect,
      the action and the effect will be perceived as being closer in time. This
      subjective temporal 'attraction' is known as intentional binding (IB). Induction
      of IB is dependent on the intentionality of one's actions, the predictability of
      the effect, and the causality between the action and the effect. Previous
      investigations of IB have utilized abstract stimuli (e.g., flashes and beeps)
      with adaptation so as to associate the abstract action-effect link. Yet, events
      from our everyday experiences already have an inherent action-effect link. We,
      thus, investigated, for the first time, IB under naturalistic, multisensory
      stimulation by manipulating the intentionality, predictability, and causal event
      link. A total of five experiments without adaptation were conducted examining IB
      with: abstract stimuli (Experiment 1), naturalistic effects (Exp. 2),
      naturalistic action cue and effect matching (Exp. 3), naturalistic action cue and
      effect mismatching (Exp. 4), and naturalistic action cue and effect matching but
      mismatched response mapping (Exp. 5). Analyses of the data showed the absence of
      IB for abstract stimuli without action-effect adaptation (Exp. 1) and for effects
      that were not inherently causal or predictable of one's action (Exp. 2, 4, and
      5). IB, however, was induced when the naturalistic sequence of action cue-effect
      was casually linked and predictable in terms of timing (Exp. 3). Overall, our
      results showed that induction of IB is dependent on the inherent causal and
      predictable association of an event from the cue to act to the consequence of
      that action, an association that is already present in everyday multisensory
      events.

PMID- 30119051
TI  - In Response.

PMID- 30119052
TI  - Nontraditional Students' Perceptions of Marginalization in Baccalaureate Nursing
      Education: Pushed to the Periphery.
AB  - BACKGROUND: Despite the continued efforts to diversify the population of nursing
      students in the United States, marginalization and attrition remain significant
      issues for nontraditional students. PURPOSE: The purpose of this study was to
      investigate the relationship between marginality and nontraditional student
      status in nursing students enrolled in a baccalaureate nursing program in Texas.
      METHOD: A nonexperimental, descriptive, correlational design was used for data
      collection. Participants (n = 192) completed a demographic survey, and
      marginality was measured using the Koci Marginality Index-70. RESULTS: There was
      a statistically significant difference in mean scores for a number of variables
      including gender, age, race/ethnicity, marital status, total household income,
      completion of a previous college degree, being a parent, and a student for whom
      English is a nonnative language. CONCLUSION: The findings from this research
      study suggest that marginalization remains a significant issue for
      nontraditional, prelicensure nursing students.

PMID- 30119050
TI  - Inhibitor of DNA Binding 2 Inhibits Epithelial-Mesenchymal Transition via Up
      Regulation of Notch3 in Breast Cancer.
AB  - Breast cancer is the second leading cause of cancer death in women worldwide.
      Incurable metastatic breast disease presents a major clinical challenge and is
      the main cause of breast cancer-related death. The epithelial-mesenchymal
      transition (EMT) is a critical early promoter of metastasis. In the present
      study, we identified a novel role for the inhibitor of DNA binding 2 (Id2), a
      member of the basic helix-loop-helix protein family, during the EMT of breast
      cancer. Expression of Id2 was positively correlated with Notch3 in breast cancer
      cells. Low expression of Id2 and Notch3 was associated with worse distant
      metastasis-free survival in breast cancer patients. The present study revealed
      that Id2 activated Notch3 expression by blocking E2A binding to an E-box motif in
      the Notch3 promoter. The Id2-mediated up-regulation of Notch3 expression at both
      the mRNA and protein levels resulted in an attenuated EMT, which was associated
      with reduced motility and matrix invasion of ER-positive and -negative human
      breast cancer cells and the emergence of E-cadherin expression and reduction in
      the mesenchymal marker vimentin in triple-negative breast cancer cells. In
      summary, our findings identified Id2 as a suppressor of the EMT and positive
      transcriptional regulator of Notch3 in breast cancer. Id2 and Notch3 may serve as
      novel prognostic markers in a subpopulation of ER-positive breast cancer
      patients.

PMID- 30119053
TI  - Using the Hybrid Operating Room in Thoracic Surgery: A Paradigm Shift.
AB  - We describe the integration of the hybrid operation room cone-beam computed
      tomography (CT) scan technology into the practice of general thoracic surgery.
      The combination of the following three techniques: (1) cone-beam CT scan
      augmented navigational bronchoscopy, (2) cone-beam CT-guided percutaneous biopsy
      and/or fiducial placement, and (3) fiducial or image-guided video-assisted
      thoracic surgery resection, into a single-stage, single-provider procedure allows
      for diagnosis and treatment in one setting. Rapid on-site evaluation of
      cytological or pathology specimens is key to this "all-in-one" approach. The time
      from diagnosis to curative treatment can significantly be reduced using the
      hybrid operation room technology, leading to decreased upstaging, increased
      survival and facilitating the otherwise difficult intraoperative detection and
      resection of small and deeper lesions. Not only does this benefit the overall
      thoracic healthcare of the community but also provides a cost-effective paradigm
      for the institution.

PMID- 30119054
TI  - Single-Stage Total Arch Replacement With Open Stent Graft for Kommerell's
      Diverticulum With Right-Sided Aortic Arch.
AB  - We treated a 70-year-old patient with Kommerell's diverticulum associated with an
      aberrant left subclavian artery and right aortic arch using single-stage total
      arch replacement with a commercially available open stent graft through only a
      median sternotomy. A four-branched prosthetic graft was implanted after insertion
      of the open stent graft through the anastomotic site under moderate hypothermia
      and cardiopulmonary bypass with selective cerebral perfusion. The aberrant
      subclavian artery was occluded by coil embolization from the distal site and
      anatomically reconstructed from the prosthetic graft. This approach is safe and
      effective and allows avoidance of a right thoracotomy and second stage
      intervention.

PMID- 30119055
TI  - 2017 Best Manuscript Awards.

PMID- 30119056
TI  - The "Paper Roll": A Simple but Useful Tool for Minimal Invasive Mitral Valve
      Repair Surgery.
AB  - During minimal invasive mitral valve repair, excessive valve tissue, as in
      myxomatous or Barlow disease, might be cumbersome to analyze and treat the
      subvalvular mitral valve apparatus. We developed a new, adaptive, flexible, and
      easy-to-use technique for better visualization of the subvalvular apparatus.
      After visualization of the mitral valve, a simple sterile paper ruler was curled
      up to a roll 1 cm in diameter and inserted through the mitral valve. By means of
      two endo forceps, the paper roll was uncurled to the desired diameter, thus
      pushing the valve leaflets away, allowing for a direct view onto the subvalvular
      apparatus. This technique was successfully used in 34 consecutive patients (mean
      +/- SD age = 57.2 +/- 11.5 years; 22 male). The calculated risk score for
      additive EuroScore, logistic EuroScore, and EuroScore II was 4 +/- 2, 3.2 +/-
      2.1, and 2.5 +/- 5.4, respectively. No patient died within the first 30 days. All
      patients presented mitral valve insufficiency grade 0 to 1 postoperatively.
      Artificial chords were implanted in all patients (3.6 +/- 1.8 chords per
      patient). This simple, adaptive, and cheap technique facilitates the approach to
      the subvalvular apparatus, especially in patients with myxomatous or Barlow
      disease. The ease of use allows for prompt approach to the papillary muscles and
      quick removal.

PMID- 30119057
TI  - Estimating Sizes of Key Populations at the National Level: Considerations for
      Study Design and Analysis.
AB  - BACKGROUND: National estimates of the sizes of key populations, including female
      sex workers, men who have sex with men, and transgender women are critical to
      inform national and international responses to the HIV pandemic. However,
      epidemiologic studies typically provide size estimates for only limited high
      priority geographic areas. This article illustrates a two-stage approach to
      obtain a national key population size estimate in the Dominican Republic using
      available estimates and publicly available contextual information. METHODS:
      Available estimates of key population size in priority areas were augmented with
      targeted additional data collection in other areas. To combine information from
      data collected at each stage, we used statistical methods for handling missing
      data, including inverse probability weights, multiple imputation, and augmented
      inverse probability weights. RESULTS: Using the augmented inverse probability
      weighting approach, which provides some protection against parametric model
      misspecification, we estimated that 3.7% (95% CI = 2.9, 4.7) of the total
      population of women in the Dominican Republic between the ages of 15 and 49 years
      were engaged in sex work, 1.2% (95% CI = 1.1, 1.3) of men aged 15-49 had sex with
      other men, and 0.19% (95% CI = 0.17, 0.21) of people assigned the male sex at
      birth were transgender. CONCLUSIONS: Viewing the size estimation of key
      populations as a missing data problem provides a framework for articulating and
      evaluating the assumptions necessary to obtain a national size estimate. In
      addition, this paradigm allows use of methods for missing data familiar to
      epidemiologists.

PMID- 30119058
TI  - Transplantation of human induced pluripotent stem cell-derived cardiomyocytes is
      superior to somatic stem cell therapy for restoring cardiac function and oxygen
      consumption in a porcine model of myocardial infarction.
AB  - BACKGROUND: Somatic stem cell (SC) therapy can improve cardiac performance
      following ischemic injury. In this study, we investigated whether induced
      pluripotent SC-derived cardiomyocytes (iPS-CMs) are more effective than somatic
      SCs, such as skeletal myoblasts (SM) and mesenchymal (M)SCs, in promoting
      functional recovery upon transplantation in a porcine model of myocardial
      infarction (MI). METHODS: Myocardial injury was induced by ameroid ring placement
      in immunosuppressed female mini-pigs; after 1 month, epicardial cell
      transplantation was performed with iPS-CMs (n = 7), SMs (n = 7), and MSCs (n =
      7). Control pigs underwent sham operation (n = 8). RESULTS: Cell therapy improved
      functional recovery 2 months after MI, as evidenced by increased ejection
      fraction (iPS-CM, +7.3% +/- 2.2% and SM, +5.8% +/- 5.4% vs. Control: -4.4% +/-
      3.8%; P < 0.05). The analysis of regional contractile function in the infarcted
      zone revealed an increase in transverse peak strain (iPS-CM, +4.6% +/- 2.2% vs.
      control, -3.8% +/- 4.7%; P < 0.05). The C-11 acetate kinetic analysis by positron
      emission tomography showed that the work-metabolic cardiac energy efficacy
      increased by the transplantation of iPS-CMs, but was reduced by the other cell
      types. This was accompanied by decreased myocardial wall stress in the infarcted
      zone (iPS-CM, -27.6 +/- 32.3 Pa and SM, -12.8 +/- 27 Pa vs. control, +40.5 +/-
      33.9 Pa; P < 0.05). CONCLUSION: The iPS-CM is superior to other somatic cell
      sources in terms of improving regional contractile function and cardiac
      bioenergetic efficiency, suggesting greater clinical benefits in severely damaged
      myocardium.This is an open-access article distributed under the terms of the
      Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC
      ND), where it is permissible to download and share the work provided it is
      properly cited. The work cannot be changed in any way or used commercially
      without permission from the journal.

PMID- 30119059
TI  - Case Report of a 63-Year-Old Patient With Alzheimer Disease and a Novel
      Presenilin 2 Mutation.

PMID- 30119060
TI  - Effectiveness of robot-assisted gait training on motor impairments in people with
      Parkinson's disease: a systematic review and meta-analysis.
AB  - The aim of this systematic review and meta-analysis was to evaluate the
      effectiveness of robot-assisted gait training (RAGT) on motor impairments in
      people with Parkinson's disease (PD). A computer-based systematic literature
      search was performed in six databases according to PRISMA guidelines. Randomized
      controlled trials (RCTs) that assessed the effects of RAGT on motor impairments
      in people with PD were included. GRADE approach and PEDro scale were used to
      determine the studies' quality of evidence. Meta-analyses were performed by
      calculating the weighted mean difference (WMD) at 95% confidence interval. Seven
      RCTs (PEDro: 5-8) met the inclusion criteria for systematic review and meta
      analyses. The meta-analysis showed significant improvement on Unified Parkinson
      Disease Rating Scale Part III after intervention [WMD=3.292; 95% confidence
      interval (CI)=1.378-5.207; P=0.000], and after 1-month follow-up (WMD=5.512; 95%
      CI=2.396-8.629; P=0.001). Stride length (WMD=9.283; 95% CI=7.153-11.414; P=0.00)
      and gait speed (WMD=0.166; 95% CI=-0.090 to 0.243; P=0.000) showed significant
      improvements after RAGT. Balance as measured by Berg Balance Scale was improved
      significantly after intervention (WMD=3.87; 95% CI=0.374-6.735; P=0.029) and at 1
      month follow-up (WMD=3.87; 95% CI=1.324-6.413; P=0.002). The pooled analysis did
      not detect any significant changes regarding stride time, cadence and functional
      balance scales. GRADE level of evidence ranged between high and low. The RAGT
      showed better outcomes than conventional interventions on some motor aspects in
      PD. However, RAGT did not seem superior to control interventions. Further RCTs
      that examine the effect of RAGT on more specific outcomes and at different
      medication statuses are required.

PMID- 30119061
TI  - Accuracy of Digital Tomosynthesis of the Chest in Detection of Interstitial Lung
      Disease Comparison With Digital Chest Radiography.
AB  - PURPOSE: The aim of the study was to assess the ability of chest digital
      tomosynthesis (DTS) for detection of interstitial lung disease (ILD) compared
      with conventional chest radiography. MATERIALS AND METHODS: We retrospectively
      reviewed 78 patients (60 males, 18 females, mean age = 53.05 years, range, 19-83
      years) who underwent chest DTS for a 5-year interval (January 1, 2009-December
      31, 2014). Of the 78 patients, 33 (42.3%) carried a diagnosis of ILD and 45
      (57.7%) were not ILD. All computed tomography reports and medical records were
      reviewed. The conventional chest radiography and DTS were separately reviewed by
      2 radiologists for the presence of ILD and the confidence in diagnosis. RESULTS:
      The diagnostic accuracy of DTS for the detection of ILD was better than
      conventional chest radiography (P < 0.05). Digital tomosynthesis had a
      sensitivity of 83.3% and negative predictive value of 89.0% that were
      statistically significantly better than conventional chest radiography (43.9% and
      70.9%, respectively). Confidence in diagnosing ILD at DTS was higher than
      conventional chest radiography (P < 0.001) and had higher interobserver agreement
      than conventional chest radiography (P < 0.01). CONCLUSIONS: Digital
      tomosynthesis improves diagnostic performance and confidence in diagnosing ILD
      compared with conventional chest radiography. Digital tomosynthesis can be
      suggested as the initial diagnostic technique for patients with suspected ILD.

PMID- 30119062
TI  - Dual-Energy Spectral Computed Tomography With Adaptive Statistical Iterative
      Reconstruction for Improving Image Quality of Portal Venography.
AB  - OBJECTIVE: The aim of the study was to investigate whether spectral computed
      tomography (CT) plus adaptive statistical iterative reconstruction (ASIR) could
      improve imaging quality of computed tomography portal venography (CTPV). METHODS:
      Sixty-four patients underwent CTPV, with CT number of portal vein (PV) less than
      150 HU in portal phase, were divided into 2 groups A (n = 31), using standard 120
      kVp protocol. group B (n = 33), using spectral CT protocol. Standard 120-kVp
      images were reconstructed with 40% ASIR, and monochromatic images at 60 keV were
      reconstructed with the following 4 ASIR percentages: 0%, 20%, 40%, and 60%. The
      CT number, image noise, and contrast-to-noise ratio in main PV were measured. The
      maximum intensity projection and volume-rendering images were used for subjective
      evaluation. These 2 kinds of results were statistically analyzed. RESULTS: The
      contrast-to-noise ratio and subjective scoring of PV increased gradually from 120
      kVp images to 60% weight ASIR (3.44 +/- 0.95, 4.58 +/- 1. 59, 5.26 +/- 1.85, 6.18
      +/- 2.18, and 7.39 +/- 2.65 and 4.35 +/- 1.17, 6.21 +/- 1.29, 6.48 +/- 1.35, 6.85
      +/- 1.28, and 7.00 +/- 1.19). There were statistically different for the 5 groups
      (P < 0.001). The CT number of the PV in the 60-kiloelectron volt spectral images
      had higher than the 120-kVp images (P < 0.001). The noise of 120 kVp was
      significantly higher than those of 60% ASIR and significantly lower than those of
      0% ASIR (both P < 0.001), and there were no significant differences between 120
      kVp, 20% ASIR, and 40% ASIR (P = 0.107 and 1.000, respectively). The diagnostic
      acceptability was highest at 40% ASIR. CONCLUSIONS: Forty-percent ASIR addition
      to the 60-kiloelectron volt monochromatic image could improve image quality of
      CTPV comparing with conventional 120-kVp images.

PMID- 30119063
TI  - The Value of 16-cm Wide-Detector Computed Tomography in Coronary Computed
      Tomography Angiography for Patients With High Heart Rate Variability.
AB  - OBJECTIVE: The aim of this study was to investigate radiation dose and image
      quality of coronary computed tomography (CT) angiography (CCTA) for patients with
      high heart rate variability (HRv) using 16-cm wide-detector CT scanner. METHODS:
      One hundred sixty-six patients with uncontrolled heart rate underwent CCTA on a
      16-cm wide-detector CT system and were divided into 2 groups based on their HRv
      for analysis: group A (n = 95, HRv <=10 beats/min [bpm]) and group B (n = 71, HRv
      >10 bpm). Images in both groups were reconstructed with motion correction
      algorithm. Subjective and objective image qualities were analyzed. RESULTS: There
      were no significant differences in age, body mass index, and heart rate (68.1 +/-
      11.4 vs 67.6 +/- 12.3 bpm) between the 2 groups (P > 0.05). However, group B had
      significantly higher HRv than group A (33.5 +/- 24.4 vs 7.8 +/- 1.2 bpm, P <
      0.001). All images were acceptable for clinical diagnosis. Compared with group A,
      image quality scores in group B decreased slightly (4.1 +/- 0.5 vs 4.0 +/- 0.6).
      However, the difference was not statistically significant. The mean effective
      doses were both relatively low at 2.2 +/- 1.1 mSv in group A and 2.6 +/- 1.4 mSv
      in group B. CONCLUSIONS: Single-heartbeat free-breathing CCTA can be performed
      for patients with high HRv using 16-cm wide-detector CT scanner to achieve
      diagnostic image quality with low radiation dose.

PMID- 30119064
TI  - Evaluation of a Computer-Aided Diagnosis System for Automated Bone Age Assessment
      in Comparison to the Greulich-Pyle Atlas Method: A Multireader Study.
AB  - OBJECTIVE: The aim of this study was to investigate a novel version of a computer
      aided diagnosis (CAD) system developed for automated bone age (BA) assessment in
      comparison to the Greulich and Pyle method, regarding its accuracy and the
      influence of carpal bones on BA assessment. METHODS: Total BA, BA of the left
      distal radius, and BA of carpal bones in 305 patients were determined
      independently by 3 blinded radiologists and assessed by the CAD system. Pearson
      product-moment correlation, Bland-Altman plot, root-mean-square deviation, and
      further agreement analyses were computed. RESULTS: Mean total BA and BA of the
      distal radius showed high correlation between both approaches (r = 0.985 and r =
      0.963). There was significantly higher correlation between values of total BA and
      BA of the distal radius (r = 0.969) compared with values of total BA and BA of
      carpal bones (r = 0.923). The assessment of carpal bones showed significantly
      lower interreader agreement compared with measurements of the distal radius
      (kappa = 0.79 vs kappa = 0.98). CONCLUSION: A novel version of a CAD system
      enables highly accurate automated BA assessment. The assessment of carpal bones
      revealed lower precision and interreader agreement. Therefore, methods
      determining BA without analyzing carpal bones may be more precise and accurate.

PMID- 30119065
TI  - Comparison of Navigator Triggering Reduced Field of View and Large Field of View
      Diffusion-Weighted Imaging of the Pancreas.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study is to compare image quality,
      presence and grade of artifacts, signal-to-noise ratio, and apparent diffusion
      coefficient (ADC) values in pancreatic tissue between high-resolution navigator
      triggered (NT) restricted field of view (rFOV) FOCUS single-shot (SS) echo-planar
      imaging (EPI) diffusion-weighted imaging (DWI) and NT large FOV SS-EPI DWI.
      MATERIALS AND METHODS: Magnetic resonance imaging examinations were performed
      with GE 3-T systems using a 32-channel body array coil. Seventeen consecutive
      patients were imaged. A 5-point scale semiquantitative grading system was used to
      evaluate image quality and general artifacts. Signal-to-noise ratio and ADC were
      measured in the head, body, and tail of the pancreas. Statistical analysis was
      performed using Student t test and Wilcoxon signed rank test, with differences
      considered significant for P value less than 0.05. RESULTS: More artifacts were
      present on large FOV compared with rFOV FOCUS SS-EPI DW images (P < 0.01).
      Restricted field of view image quality was subjectively better (P < 0.01). No
      difference in the signal-to-noise ratio was demonstrated between the 2 image
      datasets. Apparent diffusion coefficient values were significantly lower (P <
      0.01) when calculated from rFOV images than large FOV images. CONCLUSIONS: Our
      results demonstrate better image quality and reduced artifacts in rFOV images
      compared with large FOV DWI. Measurements from ADC maps derived from rFOV DWI
      show significantly lower ADC values when compared with ADC maps derived from
      large FOV DWI.

PMID- 30119066
TI  - Fetal Cardiac Functional Assessment by Fetal Heart Magnetic Resonance Imaging.
AB  - OBJECTIVE: We attempted to evaluate fetal cardiac activity of congenital heart
      disease (CHD) and normal heart fetuses by magnetic resonance imaging (MRI).
      METHODS: We evaluated the fetal cardiac functional assessment and the blood flow
      of descending aorta at 34 weeks' gestation or more by MRI and compared the
      results with ultrasonography findings. We measured 6 normal heart fetuses and 14
      CHD fetuses. RESULTS: The ejection fraction (EF) and descending aorta blood flow
      in the CHD group were 76.4% +/- 11.9%, 687.5 +/- 303.8 mL/min by ultrasonography
      and 48.3% +/- 7.1%, 711.4 +/- 273.1 mL/min by MRI; those in the normal group were
      66.9% +/- 12.2%, 898.1 +/- 245.9 mL/min by ultrasonography and 51.3% +/- 4.2%,
      911.9 +/- 223.1 mL/min by MRI. CONCLUSIONS: There was no significant difference
      in descending aorta blood flow measurements between ultrasonography and MRI, but
      the EF showed a significant between-group difference. In the normal group, the
      variation of EF and blood flow measured by MRI was significantly smaller compared
      with those of ultrasonography.

PMID- 30119068
TI  - The Old and the New: An Enhanced Vision for JNA.

PMID- 30119067
TI  - Gadoxetic Acid-Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for
      Delineation of Focal Nodular Hyperplasia: Superiority of High-Flip-Angle Imaging.
AB  - OBJECTIVE: The aim of this study was to investigate whether hepatobiliary-phase
      (HBP) flip-angle (FA) increase to 25 degrees  improves conspicuity of focal
      nodular hyperplasia (FNH) and enables HBP delay reduction. METHODS: This was a
      retrospective study of 23 patients with 46 FNHs. In each patient, HBP was
      performed with reduced-delay high FA (early/high), standard-delay high FA
      (late/high), and standard-delay standard FA (standard). Relative enhancement of
      liver and FNH periphery, FNH periphery-to-liver contrast ratio, and FNH periphery
      to-central scar contrast ratio were compared between each HBP. RESULTS:
      Early/high, late/high, and standard HBPs were performed after 13.00 +/- 2.12,
      19.12 +/- 3.10, and 19.68 +/- 3.22 minutes, respectively. Liver and FNH periphery
      relative enhancement, FNH periphery-to-liver contrast ratio, and FNH periphery-to
      central scar contrast ratio were higher for early/high and late/high than for
      standard HBP (P < 0.001 to P = 0.0048). CONCLUSIONS: Increasing FA to 25 degrees 
      improves delineation of FNHs in HBP. Combining FA increase with delay reduction
      is superior to standard HBP and is sufficient for FNH characterization.

PMID- 30119069
TI  - Preoperative Staging by EBUS in cN0/N1 Lung Cancer: Systematic Review and Meta
      Analysis.
AB  - BACKGROUND: Performance of endobronchial ultrasound-guided transbronchial needle
      aspiration (EBUS-TBNA) for staging the radiologically normal mediastinum has been
      reported with inconsistent findings. We assessed the sensitivity of systematic
      staging using EBUS-TBNA for detection of radiologically occult mediastinal
      metastases in cN0/N1 lung cancer. METHODS: Studies evaluating EBUS-TBNA for
      systematic mediastinal staging in cN0/N1 lung cancer were identified by
      systematic review. Data extracted included: participant age and sex; EBUS-TBNA
      protocol; stage determined by radiology, EBUS-TBNA and surgery; 2*2 tables.
      Primary outcome was diagnostic accuracy of EBUS-TBNA for detection of unsuspected
      N2/N3 disease. RESULTS: We identified 1173 articles. In total, 13 were included
      in a qualitative review and 9 (1146 patients) in a quantitative meta-analysis.
      Mean prevalence of N2/N3 disease was 15% (6% to 24%). EBUS-TBNA had pooled
      sensitivity of 49% [95% confidence interval (CI), 41%-57%], pooled specificity of
      100% (95% CI, 99%-100%), mean negative predictive value 91% (82% to 100%) for
      detection of unsuspected N2/N3 metastases. Number needed to test to detect occult
      N2/N3 disease was 14 (95% CI, 10.8-16.3), which halved with addition of per
      esophageal endoscopic ultrasound. CONCLUSION: Preoperative systematic staging by
      EBUS-TBNA of early lung cancer can reduce postoperative upstaging. Sensitivity
      for detection of radiologically occult mediastinal metastases seems lower than
      selective sampling of pathologic lymph nodes. Verification of negative results by
      mediastinoscopy in selected cases remains of value.

PMID- 30119070
TI  - Early Healing of Immediate Implants Connected With Two Types of Healing
      Abutments: A Prospective Cohort Study.
AB  - PURPOSE: To compare hard- and soft-tissue changes around immediate implants
      connected with 2 types of healing abutments during the early phases of healing.
      MATERIALS AND METHODS: Twenty-eight immediate implants were placed into
      molar/premolar sockets through a modified osteotomy method. The gaps around
      implants were grafted with deproteinized bovine bone mineral. According to the
      size of the alveoli, the implants were connected with titanium healing abutments
      (traditional group) or customized healing abutments (CA group). Radiographic and
      intraoral examinations were performed before surgery, postoperatively, and at the
      6-month recall. RESULTS: Buccal (P = 0.717) and lingual (P = 0.087) vertical bone
      loss was comparable between groups. More significant incomplete defect fill was
      found at the distal aspect of the CA group (P = 0.000). The buccal bone thickness
      alterations were similar between the 2 groups (P = 0.902 at the implant
      platform). The mid-facial soft-tissue level was well maintained in both groups.
      CONCLUSIONS: Within the limitations of this study, for immediate implants placed
      into posterior sockets, customized healing abutments can facilitate closure of
      large sockets. Despite more pronounced incomplete defect fill, healing abutments
      consisting of polyether ether ketone and resin did not render an increased risk
      for periimplant bone loss or soft-tissue recession during the early healing
      period.

PMID- 30119072
TI  - The Statistical Curriculum Within Randomized Controlled Trials in Critical
      Illness.
AB  - OBJECTIVES: Incomplete biostatistical knowledge among clinicians is widely
      described. This study aimed to categorize and summarize the statistical
      methodology within recent critical care randomized controlled trials. DESIGN:
      Descriptive analysis, with comparison of findings to previous work. SETTING: Ten
      high-impact clinical journals publishing trials in critical illness. SUBJECTS:
      Randomized controlled trials published between 2011 and 2015 inclusive.
      INTERVENTIONS: Data extraction from published reports. MEASUREMENTS AND MAIN
      RESULTS: The frequency and overall proportion of each statistical method
      encountered, grouped according to those used to generate each trial's primary
      outcome and separately according to underlying statistical methodology.
      Subsequent analysis compared these proportions with previously published reports.
      A total of 580 statistical tests or methods were identified within 116 original
      randomized controlled trials published between 2011 and 2015. Overall, the chi
      square test was the most commonly encountered (70/116; 60%), followed by the Cox
      proportional hazards model (63/116; 54%) and logistic regression (53/116; 46%).
      When classified according to underlying statistical assumptions, the most common
      types of analyses were tests of 2 * 2 contingency tables and nonparametric tests
      of rank order. A greater proportion of more complex methodology was observed
      compared with trial reports from previous work. CONCLUSIONS: Physicians assessing
      recent randomized controlled trials in critical illness encounter results derived
      from a substantial and potentially expanding range of biostatistical methods. In
      depth training in the assumptions and limitations of these current and emerging
      biostatistical methods may not be practically achievable for most clinicians,
      making accessible specialist biostatistical support an asset to evidence-based
      clinical practice.

PMID- 30119071
TI  - Intracranial Pressure Trajectories: A Novel Approach to Informing Severe
      Traumatic Brain Injury Phenotypes.
AB  - OBJECTIVES: Intracranial pressure in traumatic brain injury is dynamic and
      influenced by factors like injury patterns, treatments, and genetics. Existing
      studies use time invariant summary intracranial pressure measures thus
      potentially losing critical information about temporal trends. We identified
      longitudinal intracranial pressure trajectories in severe traumatic brain injury
      and evaluated whether they predicted outcome. We further interrogated the model
      to explore whether ABCC8 polymorphisms (a known cerebraledema regulator) differed
      across trajectory groups. DESIGN: Prospective observational cohort. SETTING:
      Single-center academic medical center. PATIENTS: Four-hundred four severe
      traumatic brain injury patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN
      RESULTS: We used group-based trajectory modeling to identify hourly intracranial
      pressure trajectories in days 0-5 post traumatic brain injury incorporating risk
      factor adjustment (age, sex, Glasgow Coma Scale 6score, craniectomy, primary
      hemorrhage pattern). We compared 6-month outcomes (Glasgow Outcome Scale,
      Disability Rating Scale, mortality) and ABCC8 tag-single-nucleotide polymorphisms
      associated with cerebral edema (rs2237982, rs7105832) across groups. Regression
      models determined whether trajectory groups predicted outcome. A six trajectory
      group model best fit the data, identifying cohorts differing in initial
      intracranial pressure, evolution, and number/proportion of spikes greater than 20
      mm Hg. There were pattern differences in age, hemorrhage type, and craniectomy
      rates. ABCC8 polymorphisms differed across groups. GOS (p = 0.006), Disability
      Rating Scale (p = 0.001), mortality (p < 0.0001), and rs2237982 (p = 0.035)
      differed across groups. Unfavorable outcomes were surprisingly predicted by both
      low intracranial pressure trajectories and sustained intracranial hypertension.
      Intracranial pressure variability differed across groups (p < 0.001) and may
      reflect preserved/impaired intracranial elastance/compliance. CONCLUSIONS: We
      employed a novel approach investigating longitudinal/dynamic intracranial
      pressure patterns in traumatic brain injury. In a risk adjusted model, six groups
      were identified and predicted outcomes. If validated, trajectory modeling may be
      a first step toward developing a new, granular approach for intracranial pressure
      phenotyping in conjunction with other phenotyping tools like biomarkers and
      neuroimaging. This may be particularly relevant in light of changing traumatic
      brain injury demographics toward the elderly.

PMID- 30119073
TI  - Preventing Posttraumatic Stress in ICU Survivors: A Single-Center Pilot
      Randomized Controlled Trial of ICU Diaries and Psychoeducation.
AB  - OBJECTIVES: Critical illness can have a significant psychological impact on
      patients and their families. To inform the design of a larger trial, we assessed
      feasibility of ICU diaries and psychoeducation to prevent posttraumatic stress
      disorder, depression, and anxiety following ICU stays. DESIGN: Four-arm pilot
      randomized controlled trial. SETTING: A 10-bed tertiary ICU in Winnipeg, MB,
      Canada. PATIENTS: Critically ill patients greater than 17 years old with
      predicted ICU stays greater than 72 hours and mechanical ventilation duration
      greater than 24 hours. INTERVENTIONS: Patients were randomized to usual care, ICU
      diary, psychoeducation, or both ICU diary and psychoeducation. MEASUREMENTS AND
      MAIN RESULTS: Our primary objective was to determine feasibility measured by
      enrollment/mo. Secondary outcomes included acceptability of the ICU diary
      intervention and psychological distress, including patients' memories 1 week post
      ICU using the ICU Memory Tool, posttraumatic stress disorder (Impact of Events
      Scale-Revised), depression, and anxiety symptoms (Hospital Anxiety and Depression
      Scale) 30 and 90 days post ICU. Over 3.5 years, we enrolled 58 patients, an
      average of 1.9 participants/mo. Families and healthcare providers wrote a mean of
      3.2 diary entries/d (SD, 2.9) and indicated positive attitudes and low perceived
      burden toward ICU diary participation. A majority of patients reported
      distressing memories of their ICU stay. Those who received the diary intervention
      had significantly lower median Hospital Anxiety and Depression Scale anxiety (3.0
      [interquartile range, 2-6.25] vs 8.0 [interquartile range, 7-10]; p = 0.01) and
      depression (3.0 [interquartile range, 1.75-5.25] vs 5.0 [interquartile range, 4
      9]; p = 0.04) symptom scores at 90 days than patients who did not receive a
      diary. CONCLUSIONS: ICU diaries are a feasible intervention in a tertiary
      Canadian ICU context. Preliminary evidence supports the efficacy of ICU diaries
      to reduce psychological morbidity following discharge.

PMID- 30119074
TI  - Risk Factors on Hospital Arrival for Acute Respiratory Distress Syndrome
      Following Pediatric Trauma.
AB  - OBJECTIVES: To determine risk factors identifiable at hospital arrival associated
      with acute respiratory distress syndrome development among critically injured
      children. DESIGN: Retrospective cohort study. SETTING: Level I or II adult or
      pediatric trauma centers contributing to the National Trauma Data Bank from 2007
      to 2016. PATIENTS: Patients less than 18 years admitted to an ICU with traumatic
      injury. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We determined
      associations between patient, injury, and clinical characteristics present at
      hospital arrival with development of acute respiratory distress syndrome recorded
      as a hospital complication. Acute respiratory distress syndrome occurred in 1.8%
      of 146,058 critically injured children (n = 2,590). The only demographic factor
      associated with higher risk of developing acute respiratory distress syndrome on
      multivariable analysis was African American race (relative risk, 1.42 vs white;
      95% CI, 1.13-1.78). Injury characteristics included firearm injuries (relative
      risk 1.93; 1.50-2.48) and motor vehicle crashes (relative risk, 1.91; 1.57-2.31)
      relative to falls; spine (relative risk, 1.39; 1.20-1.60), chest (relative risk,
      1.36; 1.22-1.52), or lower extremity injuries (relative risk, 1.26; 1.10-1.44);
      amputations (relative risk, 2.10; 1.51-2.91); and more severe injury (relative
      risk, 3.69 for Injury Severity Score 40-75 vs 1-8; 2.50-5.44). Clinical variables
      included abnormal respiratory status (intubated relative risk, 1.67; 1.23-2.26
      and hypopnea relative risk, 1.23; 1.05-1.45 and tachypnea relative risk, 1.26;
      1.10-1.44) and lower Glasgow Coma Scale score (relative risk, 5.61 for Glasgow
      Coma Scale score 3 vs 15; 4.44-7.07). CONCLUSIONS: We provide the first
      description of the incidence of and risk factors for acute respiratory distress
      syndrome among pediatric trauma patients. Improved understanding of the risk
      factors associated with acute respiratory distress syndrome following pediatric
      trauma may help providers anticipate its development and intervene early to
      improve outcomes for severely injured children.

PMID- 30119075
TI  - Rheumatoid Arthritis-Associated Orbital Vasculitis.
AB  - A patient with a history of rheumatoid arthritis presented with bilateral orbital
      lesions while on abatacept. Biopsy of the lesions yielded pathologic assessment
      showing vasculitis with a mixed inflammatory infiltrate notable for numerous
      eosinophils. Despite initial improvement on cyclophosphamide therapy, she
      developed progression of the orbital lesions and lesions elsewhere on her body.
      All serologic studies were normal except for increased levels of rheumatoid
      factor and eosinophilia. The patient underwent a second biopsy, which was
      consistent with her initial pathology. The patient was started on high-dose
      mycophenolate mofetil treatment with a good response. After 1 year of treatment,
      the patient's lesions have nearly completely resolved. This patient illustrates
      the diagnostic and therapeutic challenges encountered when treating orbital
      vasculitis. Furthermore, this case shows the importance of not categorizing
      vasculitis with unclear etiology under the umbrella diagnosis of atypical
      granulomatosis with polyangiitis. This patient did not exhibit the serologic or
      pathologic characteristics of granulomatosis with polyangiitis, and she did not
      respond to treatment as would be expected for granulomatosis with polyangiitis.
      Maintaining an open approach to diagnosis and treatment was crucial in obtaining
      a favorable outcome for this patient.

PMID- 30119076
TI  - Population Pharmacokinetic-Pharmacodynamic Modeling of a Novel Methylphenidate
      Extended-Release Orally Disintegrating Tablet in Pediatric Patients With
      Attention-Deficit/Hyperactivity Disorder.
AB  - PURPOSE/BACKGROUND: A methylphenidate (MPH) extended-release orally
      disintegrating tablet (MPH XR-ODT) formulation was recently approved for
      attention-deficit/hyperactivity disorder treatment in children 6 to 17 years of
      age. This analysis sought to develop a population pharmacokinetic
      (PK)/pharmacodynamic (PD) model to describe MPH XR-ODT PD-response data in a
      classroom study and use the model to simulate PD responses for a range of body
      weights and doses. METHODS/PROCEDURES: The MPH XR-ODT PK/PD model was developed
      with pediatric and adult PK data from prior studies and efficacy data from a
      laboratory classroom study in children with attention-deficit/hyperactivity
      disorder. In these studies, the safety profile of MPH XR-ODT was consistent with
      other extended-release MPH formulations. The PK/PD model efficacy end point was
      the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale Combined score. Body weight
      effects on MPH clearance and volume of distribution were included in the
      resulting model. Simulations using the PK/PD model were performed for patients
      with body weights between 7 and 100 kg and MPH XR-ODT doses of 10 to 60 mg MPH
      hydrochloride equivalents. FINDINGS/RESULTS: In the PK/PD model, the maximal
      reduction in the Swanson, Kotkin, Agler, M-Flynn, and Pelham Scale Combined score
      was approximately 38 units, and the MPH concentration required to achieve 50% of
      the maximal reduction was 14.24 ng/mL, suggesting favorable efficacy for MPH XR
      ODT. Simulations showed a direct correlation between the effective MPH XR-ODT
      dose and body weight, with heavier participants requiring higher doses for
      symptom control. IMPLICATIONS/CONCLUSION: This model may help facilitate the dose
      titration process by identifying an effective MPH XR-ODT target dose.

PMID- 30119078
TI  - Introduction by the Guest Editors: Bevacizumab.

PMID- 30119077
TI  - Added Value of Whole-Exome and Transcriptome Sequencing for Clinical Molecular
      Screenings of Advanced Cancer Patients With Solid Tumors.
AB  - Comprehensive genomic profiling using high-throughput sequencing brings a wealth
      of information, and its place in the clinical setting has been increasingly
      prominent. This review emphasizes the utility of whole-exome sequencing (WES) and
      transcriptome sequencing (RNAseq) in patient care and clinical research, based on
      published reports as well as our experience with the MOSCATO-01 (MOlecular
      Screening for CAncer Treatment Optimization) molecular triage trial at Gustave
      Roussy Cancer Center. In this trial, all contributive samples of patients with
      advanced solid tumors were analyzed prospectively with targeted gene sequencing
      (TGS) and comparative genomic hybridization. In addition, 92 consecutive
      metastatic patients with contributive biopsies were sequenced for WES and RNAseq
      and compared with TGS and comparative genomic hybridization. Whole-exome
      sequencing allowed the reporting of additional variants in relevant genes in 38%
      of patients. Mutation detection sensitivity of WES was 95% compared with TGS.
      Additional information derived from WES and RNAseq could influence clinical
      decision, including fusion transcripts, expression levels, allele-specific
      expression, alternate transcripts, RNA-based pathogen diagnostic, tumor mutation
      load, mutational signatures, expression signatures, HLA genotyping, and
      neoepitope prediction. The current challenge is to be able to process the large
      scale data from these comprehensive genome-wide technologies in an efficient way.

PMID- 30119079
TI  - Antiangiogenic Therapy in Colorectal Cancer.
AB  - Colorectal carcinoma is the third most common cancer worldwide. Approximately 20%
      of patients with colorectal cancer will have metastatic disease at the time of
      initial diagnosis, and approximately 30% to 50% of patients with primary colon
      cancer will relapse and die of metastatic cancer. The 5-year survival rate of
      metastatic colorectal cancer remains disappointing at approximately
      10%.Angiogenesis plays a significant role in tumor growth and metastasis in
      colorectal carcinoma. There are currently 4 US Food and Drug Administration
      approved antiangiogenic agents for metastatic colorectal cancer. Bevacizumab is
      the only antiangiogenic agent approved by the US Food and Drug Administration for
      first-line treatment of metastatic colorectal cancer. Other antiangiogenic agents
      include ramucirumab, ziv-aflibercept, and regorafenib. We review the data
      supporting the use of antiangiogenics in this disease.

PMID- 30119080
TI  - Combinations of Bevacizumab With Immune Checkpoint Inhibitors in Renal Cell
      Carcinoma.
AB  - Renal cell carcinoma (RCC) is characterized by aberrant angiogenic signaling and
      an immunogenic tumor microenvironment. Systemic therapies targeting vascular
      endothelial growth factor and the immune checkpoints programmed cell death
      protein 1/programmed cell death protein 1 ligand and cytotoxic T-lymphocyte
      associated protein 4 have advanced to the forefront of the treatment repertoire
      against advanced or metastatic RCC (mRCC). In preclinical models, inhibition of
      vascular endothelial growth factor signaling promotes antitumor immunity and may
      enhance the efficacy of immune checkpoint blockade. Bevacizumab, which has
      previously shown antitumor activity in mRCC as monotherapy and in combination
      with interferon alpha, is now under investigation in clinical trials in
      combinations involving multiple immune checkpoint inhibitors. The combination of
      bevacizumab plus atezolizumab has demonstrated efficacy in a randomized phase III
      study of treatment-naive mRCC patients whose tumors express programmed cell death
      protein 1 ligand. We review here the preclinical rationale for combining
      antiangiogenic therapies with immune checkpoint inhibitors and highlight the
      status of current clinical development of combinations involving bevacizumab and
      immune checkpoint inhibitors in RCC.

PMID- 30119081
TI  - Bevacizumab and Glioblastoma: Past, Present, and Future Directions.
AB  - Glioblastoma (GBM) is the most common and lethal intracranial malignancy, with
      few advances in treatment over the last several decades. Much excitement
      surrounded the initial approval for bevacizumab for recurrent GBM, given the
      marked radiographic responses and improvement in progression-free survival
      observed in early studies. However, phase III studies have failed to demonstrate
      an overall survival advantage with the use of this agent. An overview of the
      mechanism of action and activity of bevacizumab in adult gliomas, a timeline of
      pivotal clinical trials, data on its impact on quality of life and imaging, and
      its role in managing the sequelae of treatment provide evidence for its current
      use. Investigations into combinatorial approaches utilizing bevacizumab with
      reirradiation and immunotherapy and ongoing work to identify biomarkers to select
      patient subsets who may benefit from treatment elucidate important unanswered
      questions that will further define the role of bevacizumab in the management of
      patients with GBM.

PMID- 30119082
TI  - Bevacizumab in Cervical Cancer: 5 Years After.
AB  - Over the past 5 years, addition of bevacizumab to combination chemotherapy for
      advanced, recurrent, and persistent cervical cancer has offered prolonged overall
      and progression-free survival. Since the original press release announcing the
      survival benefits of this antiangiogenesis therapy, there has been further study
      of bevacizumab related to quality of life, combination with other agents, use of
      imaging to evaluate likelihood of response, and development of biosimilars. This
      review summarizes publications related to bevacizumab use in advanced, recurrent,
      and persistent cervical cancer over the past 5 years since initial proof of
      concept of antiangiogenesis therapy and the initial dissemination of information
      regarding survival benefits of bevacizumab.

PMID- 30119083
TI  - Combinations of Bevacizumab With Cancer Immunotherapy.
AB  - Cancer immunotherapy (CIT) has transformed cancer treatment. In particular,
      immunotherapies targeting the programmed death ligand 1 (PD-L1)/programmed death
      1 pathway have demonstrated durable clinical benefit in some patients. However,
      CIT combinations may create a more favorable environment in which to maximize the
      potential of the immune system to eliminate cancer. Here we describe 3 key
      mechanisms related to vascular endothelial growth factor (VEGF)-mediated
      immunosuppression: inhibition of dendritic cell maturation, reduction of T-cell
      tumor infiltration, and promotion of inhibitory cells in the tumor
      microenvironment; supporting data are also described. In addition, we discuss
      immunomodulatory properties observed within tumors following bevacizumab
      treatment. Combining anti-PD-L1 and anti-VEGF therapies has shown synergy and
      positive outcomes in phases I to III studies, particularly in settings where high
      VEGF levels are known to play an important role in tumor growth. We also review
      data from key studies supporting combination of bevacizumab and CIT, with a focus
      on PD-L1/programmed death 1 inhibitors.

PMID- 30119084
TI  - American Football Players in Preseason Training at Risk of Acute Kidney Injury
      Without Signs of Rhabdomyolysis.
AB  - OBJECTIVE: This study was designed to identify changes in blood biomarkers that
      would indicate excessive muscle breakdown during the initial 10 days of preseason
      training in collegiate American football players and subsequently increase their
      risk of acute kidney injury (AKI). DESIGN: Prospective cohort study. SETTING:
      Preseason, heat acclimatization period. PARTICIPANTS: Twenty-five Division I
      American football players. INTERVENTION: Clinical biomarkers for muscle damage
      were measured during a preseason training camp. Samples were obtained before camp
      and approximately 5 and 10 days into camp after completion of heat
      acclimatization training. MAIN OUTCOMES: Creatine kinase, myoglobin, lactate
      dehydrogenase, and creatinine were measured. Glomerular filtration rate (GFR) was
      calculated. Urine was collected at each blood draw to qualitatively identify
      hematuria and red blood cells. RESULTS: A high percentage of athletes had an
      asymptomatic reduction in kidney function over the 10-day period. Ten of 23
      athletes did have a significant, 31.6%, mean reduction in GFR, placing each at
      risk of AKI according to Risk, Injury, Failure, Loss of kidney function, and End
      stage kidney disease (RIFLE) classification. The plasma myoglobin for the at risk
      of AKI group had a mean value 8* above their baseline mean on day 5 and
      statistically significant mean 13* higher on day 10 than baseline. The not at
      risk of AKI group did not have significant differences between days 0, 5, and 10.
      CONCLUSIONS: A relatively high percentage of athletes had an asymptomatic
      reduction in kidney function during the intense preseason training period. 43.4%
      of athletes in this study had a significant 31.6% mean reduction in GFR over the
      10 days. According to RIFLE classification, this placed each athlete "at risk" of
      AKI.

PMID- 30119085
TI  - Sport Preparticipation Screening for Asymptomatic Atlantoaxial Instability in
      Patients With Down Syndrome.
AB  - Down syndrome (DS) is a clinical syndrome comprising typical facial features and
      various physical and intellectual disabilities due to extra genetic material on
      chromosome 21, with one in every 1000 babies born in the United Kingdom affected.
      Patients with Down syndrome are at risk of atlantoaxial instability (AAI).
      Although AAI can occur in other conditions, such as rheumatoid arthritis, this
      position statement deals specifically with patients with DS and asymptomatic AAI.
      Atlantoaxial instability, also referred to as atlantoaxial subluxation, is
      defined as increased movement between the first (atlas) and second (axial)
      cervical vertebra joint articulation, the atlantoaxial joint. Atlantoaxial
      instability is reported to occur in 6.8% to 27% of the DS population, although
      this varies depending on the age of the patients whom you are screening. Less
      than 1% to 2% of these patients are then thought to later develop symptomatic
      AAI, although the natural history and progression of AAI is not well understood.
      The risks associated with AAI are neurological injury from excessive movement of
      the cervical vertebra impinging on and then damaging the spinal cord, although
      the risk of this during sporting activities is extremely rare. Clearly, physical
      activity and sports participation for patients with DS has many biological,
      psychological, and social benefits, and the Faculty of Sport and Exercise
      Medicine (FSEM), United Kingdom, wishes to promote safe physical activity and
      sport for all. The FSEM, United Kingdom, has therefore produced a statement
      regarding sport preparticipation screening for asymptomatic AAI in patients with
      DS.

PMID- 30119086
TI  - Is It Time to Give Athletes a Voice in the Dissemination Strategies of Concussion
      Related Information? Exploratory Examination of 2444 Adolescent Athletes.
AB  - OBJECTIVE: The objective of the research was to screen male and female adolescent
      athletes on their concussion educational histories and preferred future methods
      of education in terms of educational messenger, modality, and concussion-related
      areas of interest. DESIGN: Cross-sectional survey. SETTING: Examination setting
      within the classroom. PARTICIPANTS: Adolescent male (n = 1854) and female (n =
      590) athletes aged 12 to 18 years. MAIN OUTCOME MEASURES: To explore the
      concussion educational histories and preferred future methods of education in
      Irish male and female adolescent athletes. RESULTS: 19.7% (n = 482) of the sample
      received education in the past 12 months. Male athletes had a significantly
      higher rate of previous education than female athletes (41% vs 17%). The methods
      used in previous educational interventions are failing to match the interests of
      the athletes. Sex played a significant role in the preferred educational methods,
      as male and female athletes had significant differences in their choice of
      educational messenger, modality, and concussion-related areas of interest.
      CONCLUSIONS: The current disparity in previous concussion education rates between
      male and female adolescent athletes should be addressed. Forthcoming research
      should explore the efficacy of tailoring knowledge translation strategies to
      match the specific needs of the recipient.

PMID- 30119087
TI  - Integrated Rehabilitation for Breast Cancer Survivors.
AB  - The physical and psychological side effects of breast cancer therapies can have
      substantial impact on survivors' physical and social functioning. Roughly half of
      the more than 3 million Americans alive with a history of breast cancer report
      adverse, function-degrading sequelae related to their oncologic treatments. Care
      delivery models for the timely delivery of rehabilitation services have been
      proposed yet limitedly vetted or implemented. These include the prospective
      surveillance model, procedure-linked referrals, survivorship care plans and risk
      stratification. Patients' capacity to engage in the rehabilitative process varies
      over the course of cancer therapy and into survivorship. Perioperative attention
      generally focuses on managing premorbid impairments and normalizing shoulder
      function. In contrast, during chemo- and radiation therapies, symptom control,
      constructive coping, and role preservation may become more salient. Risk
      stratified, individualized screening and prevention activities for specific
      impairments have become increasingly feasible through predictive models and
      analytics. Impairments' severity deleterious impact can be mitigated, as has been
      established for lymphedema, shoulder dysfunction, chemotherapy-induced peripheral
      neuropathy, cognitive dysfunction, fatigue, and sexual side effects. Integrated
      rehabilitative programs, often initiated following the completion of cancer
      treatment, are available in some countries outside of the United States and may
      offer survivors vital vocation- and avocation-directed services.

PMID- 30119088
TI  - A tale of confusion from overlapping confidence intervals: brief report.
AB  - In clinical research presentations, study results are commonly reported in the
      form of p-values and confidence intervals as an estimate of association and
      treatment effect. The interpretation of confidence intervals that overlap can be
      confusing and difficult for the reader to draw clinically meaningful conclusions.
      In this brief report, we describe the basics of confidence intervals and present
      an example from a recently published randomized control trial (RCT) to illustrate
      a common confusion that overlapping confidence intervals between the means of two
      independent groups may not necessarily reject the true significant difference of
      effect. It is recommended that investigators use the direct difference of means
      between groups for confidence interval estimation to reduce Type II errors.
      Clinicians should interpret overlapping confidence intervals with caution, and
      avoid the assumption that overlapping confidence intervals always implies a lack
      of difference of treatment effect to decide application of treatment.

PMID- 30119089
TI  - Complete Restoration of Respiratory Muscle Function in Three Subjects with Spinal
      Cord Injury Pilot Interventional Clinical Trial.
AB  - OBJECTIVES: To assess the safety and efficacy of complete restoration of
      respiratory muscle function in subjects with Spinal Cord Injury (SCI). METHODS:
      This was an interventional study investigating three subjects maintained on a
      diaphragm pacing system who were implanted with the spinal cord stimulation (SCS)
      system to restore cough. Peak expiratory airflow and airway pressure generation
      were the primary physiologic outcome measures; an assessment of the degree of
      difficulty in raising secretions was the primary clinical outcome measure.
      RESULTS: Mean peak expiratory airflow and airway pressure generation during
      spontaneous efforts were 1.7+/-0.2L/s and 31+/-7cmH2O respectively. When SCS was
      applied following pacing volume associated with the subject's maximum inspiratory
      effort and synchronized with the subject's maximum expiratory effort, peak
      expiratory airflow and airway pressure generation were 9.0+/-1.9 and 90+/-6cmH2O,
      respectively (p<0.05). Moreover, each subject experienced much greater ease in
      raising secretions and marked improvement in the ease in raising secretions
      compared to other methods. CONCLUSIONS: Complete restoration of respiratory
      muscle function can be safely and effectively achieved in the same individuals
      with SCI. SCS results in peak expiratory airflow and airway pressure generation
      characteristic of a normal cough while diaphragm pacing was successful in
      maintaining patients off mechanical ventilation.

PMID- 30119090
TI  - Probiotics and Evidence-based Medicine: To All Involved: We have a Problem.
AB  - The methods used to discern the structure (anatomy) and function (physiology) of
      the indigenous microbiota can be divided according to which aspect of the
      microbiota they can interrogate and are positioned accordingly. At the most basic
      level, methods can simply describe the community structure of the microbiota,
      that is, which taxa are present and in what relative amounts. Methods that
      investigate functional potential generally catalog the coding potential of
      individual members of the microbiota or the entire community (the metagenome). To
      measure function directly a catalog of the expressed microbial genes (the
      metatranscriptome) or the proteins or metabolites present in the microbiome
      environment must be generated. So, complexity in understanding the role of
      microbiota is quite rejecting the interested clinician. Evidence-based medicine
      can offer an answer suggesting strict definition of populations, measurement
      techniques, and external validity.

PMID- 30119091
TI  - Effect of Acid Suppression on Peripheral T-Lymphocyte Subsets and
      Immunohistochemical Esophageal Mucosal Changes in Patients With Gastroesophageal
      Reflux Disease.
AB  - BACKGROUND AND AIMS: Gastroesophageal reflux disease (GERD) is a common prevalent
      disease. We aimed to assess the dynamic changes in the peripheral T lymphocytes
      and lymphocytes infiltrating the esophageal mucosa after treatment with proton
      pump inhibitor (PPI) in patients with GERD. PATIENTS AND METHODS: A total of 200
      patients who presented with upper GIT symptoms were included in this prospective
      study. All patients were subjected to full history taking, clinical examination,
      and complete blood count. Upper endoscopy was performed to detect the grade of
      GERD, followed by 4 quadrant biopsies before and 1 month after acid suppressive
      drug therapy. Histopathologic and immunohistochemical examination were carried
      out for all biopsies. Flow cytometry analysis for the peripheral T lymphocytes
      and cytokine profile assay before therapy and after therapy were also carried
      out. RESULTS: In total, 200 patients comprising 132 male individuals (66%) and 68
      female individuals (34%) with a mean age of 47.9+/-18.3 were included. The risk
      factors for development of GERD were smoking in 87 (43.5%), spicy food intake in
      26 (13%), analgesics in 46 (23%), excessive tea and coffee in 35 (17.5%), and
      nondetected risk factors in 6 (3%). Endoscopic examination using Los Angeles
      grading system revealed that 102 patients (51%) were grade A, 57 patients (28.5%)
      were grade B, 38 patients (19%) were grade C, and 3 patients (1.5%) were grade D.
      No statistically significant differences could be detected in HGB levels and WBC,
      PLT, monocyte, granulocyte, and eosinophil counts before and after treatment with
      PPI. Histopathologic examination of esophageal biopsies showed significant
      posttreatment improvement in 132 cases (66%); however, 66 cases (33%) including
      the 2 cases (1%) of Barrett's esophagus showed nonsignificant pathologic
      improvement compared with the pretreatment picture. Immunohistochemical staining
      of esophageal biopsies with CD3 (T-cell marker) and CD20 (B-cell marker), before
      and 1 month after treatment, showed the presence of a very large number of
      infiltrating B cells in the esophageal mucosa (700+/-30/10 HPF) with large
      aggregations; in contrast, T-cell infiltration appeared less marked (570+/-23/10
      HPF), and they formed smaller aggregates than those of B cells in pretreated
      patients, with P<0.01. However, 1 month after treatment with PPI, esophageal
      biopsies revealed a marked decrease in the number of both B (10+/-2/10 HPF) and T
      (290+/-12/HPF) cells in 66% of patients, with a P<0.01 in comparison with the
      pretherapy pattern. However, the remaining 33% of patients still showed a
      significantly high number of T cells (490+/-28/HPF), with a P <0.05 in comparison
      with the responder group that formed small aggregates with larger cell sizes,
      indicating their activation. Cytokine profiles before and after treatment
      revealed significant posttreatment reduction in their levels in the 132 cases
      with improvement in their clinical manifestations, and endoscopic and
      histopathologic findings, but there is no obvious change in the measured cytokine
      levels in 66 patients who simultaneously had no improvement in their endoscopic,
      histopathologic findings and mild improvement in their clinical manifestations.
      Moreover, significant posttreatment reduction of IL-8 and IL-1beta in the 98
      (49%) patients with Los Angeles grading B, C, and D was observed. With regard to
      serum levels of IL-10 and IL-4, there were no statistically significant
      differences before and after treatment with PPI. Peripheral blood immunologic
      parameters revealed a statistically significant reduction of the total CD3
      absolute count, T-helper lymphocyte (CD4/CD3) percentage, T-helper lymphocyte
      absolute count, and the percentage and absolute cytotoxic T-lymphocyte count
      (CD8/CD3) after treatment with PPI. Moreover, the same significant difference of
      peripheral blood lymphocytes was detected after exclusion of patients with Los
      Angeles grade A, which may be considered normal. CONCLUSIONS: Acid-induced T-cell
      related cytokine production plays an important role in inflammation occurring in
      patients with GERD. Mucosal and peripheral inflammation reduces with PPI use.

PMID- 30119092
TI  - Temporal Trends and Risk Factors for Postcolonoscopy Colorectal Cancer.
AB  - BACKGROUND: Colonoscopy is effective for colorectal cancer (CRC) prevention, yet
      patients may develop CRC despite adhering to screening/surveillance intervals.
      There are limited data on predictive factors associated with these
      postcolonoscopy CRCs (PCCRCs). We aimed to measure PCCRC rates and identify risk
      factors for PCCRC. METHODS: We performed a case-control study, comparing patients
      with PCCRCs to spontaneous CRCs diagnosed during a 12.5-year period at an
      academic medical center. PCCRCs were defined as CRCs diagnosed in between
      guideline-recommended screening/surveillance intervals. RESULTS: During the 12.5
      year period, of 1266 CRCs diagnosed, 122 (10%) were PCCRCs. 70% of PCCRCs were
      diagnosed within 5 years of a prior colonoscopy. There was an increasing trend
      for PCCRC rates in recent years [odds ratio (OR), 2.78; 95% confidence interval
      (CI), 1.51-5.09], with PCCRCs comprising 13.6% of cancers diagnosed in 2016 as
      compared with 5.7% of cancers diagnosed in 2005. Older age (OR per year, 1.02;
      95% CI, 1.01-1.04), proximal colonic location (OR, 1.99; 95% CI, 1.20-3.33) and
      early stage (OR, 2.57; 95% CI, 1.34-4.95) were associated with PCCRCs. In total,
      41% of PCCRCs were diagnosed by a different physician from the physician who did
      the prior colonoscopy, and 42% of physicians did not diagnose any of their PCCRC
      cases. CONCLUSIONS: PCCRC rates are rising in recent years, likely reflecting the
      widespread adoption of colonoscopy as a primary screening tool, and are more
      common in older patients and those with proximal, early-stage tumors. The finding
      that a large proportion of PCCRCs are diagnosed by a different physician raises
      the concern that physicians are unaware of their own patients' PCCRCs.

PMID- 30119093
TI  - Does Weekend Hospital Admission Affect Upper Gastrointestinal Hemorrhage
      Outcomes?: A Systematic Review and Network Meta-Analysis.
AB  - BACKGROUND: Compared with weekday admissions, weekend admissions are consistently
      associated with worse patient outcomes, known as the "weekend effect." The
      weekend effect may have adverse health consequences, including death. To
      determine the potential impact of the weekend effect on primary (ie, mortality)
      and secondary outcomes of patients with upper gastrointestinal hemorrhage (UGIH).
      MATERIALS AND METHODS: This was a network meta-analysis based on cohort studies.
      Databases were searched for studies published up to April 2018. The predefined
      primary outcome was mortality (30-d mortality and in-hospital mortality). The
      secondary efficacy outcomes were rebleeding rates, use of endoscopic therapy,
      need for surgery or angiography, mean length of hospital stay, and time to
      endoscopy. The study protocol was registered with PROSPERO (No. CRD42018094660).
      RESULTS: In total, 25 studies, including 28 analyses (N=1,203,202 patients), were
      eligible. The results revealed a tendency toward increased 30-day mortality and
      increased in-hospital mortality among weekend admissions. In a subgroup analysis,
      there were significance differences in mortality according to the study location
      (ie, Europe) and UGIH type (ie, variceal UGIH), with these subgroups having
      elevated mortality rates. Moreover, weekday admissions were associated with a
      significant decrease in rebleeding rates. In the network meta-analysis, the study
      location (in Europe or Asia) and type of UGIH (ie, variceal UGIH) were associated
      with an increased likelihood of high in-hospital mortality among weekend
      admissions. CONCLUSIONS: The evidence derived from this network meta-analysis
      supports the idea that weekend admissions are associated with an increased risk
      of death, especially among variceal UGIH patients in European hospitals.

PMID- 30119096
TI  - Neoplastic disease after acute coronary syndrome: incidence, duration, and
      features: the ABC-4* Study on Heart Disease.
AB  - AIM: To investigate the clinical features and incidence of malignant neoplasia
      during 17 years of follow-up in an unselected sample of patients with acute
      coronary syndrome (ACS). METHODS: The Adria, Bassano, Conegliano, and Padova
      Hospital-4 Study on Heart Disease is an ongoing, prospective study of an unbiased
      population of patients with ACS. Baseline clinical and laboratory data were
      obtained during the first 7 days of hospitalization at three different intensive
      coronary care units. The current study included data from 589 patients with ACS.
      RESULTS: At enrollment, 19 patients had confirmed neoplasia. During follow-up, 99
      additional patients developed malignant neoplastic disease. The incidence rate
      was 17.8 cases per 1000 person-years, which was about three times higher than
      that observed in the general population. Patients had a shorter duration of
      neoplasia when they developed it after enrollment compared with those with
      preexisting neoplasia [hazard ratio = 2.0 (1.5-2.6), P = 0.001]. Patients with
      neoplasia who died during follow-up had an earlier onset of neoplasia [hazard
      ratio = 1.8 (1.1-2.9), P = 0.01] and shorter duration than survivors [hazard
      ratio = 4.1 (2.4-7.0), P < 0.0001]. The estimated time to diagnosis of neoplasia
      indicated elderly patients had a significantly higher risk than younger people
      during the 17 years of follow-up. After the onset of neoplasia, survival time
      declined more sharply in the elderly than younger people. CONCLUSION: The long
      term prospective study showed that patients with ACS have a higher incidence of
      malignancy than the general population. Those who develop neoplasm after being
      diagnosed with ACS have a worse prognosis than patients with a preexisting
      neoplasia.

PMID- 30119094
TI  - The Association Between the Functional Status Scale and the Pediatric Functional
      Independence Measure in Children Who Survive Traumatic Brain Injury.
AB  - OBJECTIVES: To determine the association between the Functional Status Scale and
      Pediatric Functional Independence Measure scores during the rehabilitation stay
      in children who survive traumatic brain injury. DESIGN: Secondary analysis of a
      prospective observational cohort study. SETTING: Tertiary care children's
      hospital with a level 1 trauma center and inpatient rehabilitation service.
      PATIENTS: Sixty-five children less than 18 years old admitted to an ICU with
      acute traumatic brain injury and subsequently transferred to the inpatient
      rehabilitation service. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN
      RESULTS: Functional Status Scale and Pediatric Functional Independence Measure at
      transfer to rehabilitation and Pediatric Functional Independence Measure at
      discharge from rehabilitation. The median age of the cohort was 7.1 years
      (interquartile range, 0.8-12.3 yr), and 29% were female. Nearly all of the
      children were healthy prior to the traumatic brain injury: six patients (9.2%)
      had a baseline Functional Status Scale score greater than 6. At the time of
      transfer to inpatient rehabilitation, total Functional Status Scale and Pediatric
      Functional Independence Measure scores had the expected negative correlation due
      to increasing disability resulting in lower scores in Pediatric Functional
      Independence Measure and higher scores in Functional Status Scale (r = -0.49; 95%
      CI, -0.62 to -0.35). Among subjects with less disability as measured by lower
      total Functional Status Scale scores, we found substantial variability in the
      total Pediatric Functional Independence Measure scores. In contrast, Pediatric
      Functional Independence Measure scores were consistently low among subjects with
      a wide range of higher total Functional Status Scale scores (more disability).
      CONCLUSIONS: Although proprietary and more time-intensive, the Pediatric
      Functional Independence Measure has advantages relative to the Functional Status
      Scale for less severely injured patients and task-specific measurements. The
      Functional Status Scale may have advantages relative to the Pediatric Functional
      Independence Measure for more severely injured patients. Further investigations
      are needed to characterize changes in the Functional Status Scale during the
      rehabilitation stay and after discharge.

PMID- 30119097
TI  - Outcome of the multidimensional prognostic index in ultra-octogenarian patients
      hospitalized for cardiovascular diseases.
AB  - BACKGROUND: The multidimensional prognostic index (MPI) is a validated tool for
      prognostic stratification in acute and chronic setting of geriatric patients.
      However, only few data are available on patients with cardiovascular diseases.
      AIM: To evaluate the potential role of MPI as predictor of 1-year and long-term
      outcome in ultra-octogenarians patients hospitalized for cardiovascular diseases.
      METHODS AND RESULTS: We conducted a prospective study on 216 patients (mean age
      85 +/- 4 years) hospitalized for cardiovascular disease enrolled from September
      2011 to February 2014 in both Cardiology and Internal Medicine Departments. The
      mean follow-up was 33 +/- 7 months. The primary end-point was 1-year all-cause
      mortality. In addition, 3-year all-cause mortality was also assessed in the
      overall cohort and outcome prediction was then evaluated separately in patients
      with a primary diagnosis of heart failure and acute coronary syndrome. At
      admission, 53% of patients had a MPI-1 low risk, 34% had a MPI-2 moderate risk
      and 13% had a MPI-3 high risk (13%). Internal medicine inpatients had worse risk
      profile and higher MPI risk class than patients admitted to the cardiovascular
      department. Fifty-four patients (25%) experienced the primary end-point. In the
      multivariate logistic regression model MPI score [hazard ratio (HR) 1.83, 95%
      confidence interval (CI) 1.23-2.71, P = 0.003], serum creatinine (HR 1.32, 95% CI
      1.13-1.54, P < 0.001) and serum albumin (HR 0.43, 95% CI, P = 0.04) were
      independent predictors of 1-year mortality. The area under the receiver operating
      characteristic combining the MPI score with serum creatinine and albumin was 0.83
      (CI 0.15-0.59, P < 0.001). CONCLUSION: In ultra-octogenarian inpatients
      hospitalized for cardiovascular disease, MPI score independently predicts a
      poorer outcome. An integrated model including MPI, serum creatinine and albumine
      might aid the prognostic stratification of hospitalized elderly populations.

PMID- 30119098
TI  - Contribution of Oral Hygiene and Cosmetics on Contamination of Gluten-Free Diet:
      Do Celiac Customers Need to Worry About?
AB  - OBJECTIVES: The only available treatment for celiac disease (CD) is the gluten
      free diet. It is unclear whether the presence of gluten in oral hygiene products
      and cosmetics that are applied on the mouth is a reason of concern for CD
      patients. The aim of this study was to test the level of gluten contamination in
      oral hygiene and cosmetic products available in the Italian market. METHODS: A
      total of 66 products (toothpastes = 37; dental tablets = 2; mouthwashes = 5; lip
      balms = 10; lipsticks = 12) labelled gluten-free or with unknown gluten content
      were randomly collected from different supermarkets and pharmacies. The gluten
      quantification was determined by the R5 ELISA method approved by EU regulations.
      RESULTS: Out of 66 oral hygiene and cosmetics, 62 products (94%) were found to be
      gluten-free (gluten level <20 ppm), while 4 (6%) (toothpastes = 3; lipsticks = 1)
      showed a gluten level >20 ppm (toothpastes: 20.7 ppm, 31.4 ppm, and 35 ppm;
      lipstick: 27.4 ppm). None of the selected products had ingredient derived from
      wheat, barley, or rye. CONCLUSIONS: Gluten contamination is currently not an
      issue in a wide array of cosmetic and oral hygiene products that are commonly on
      the market.

PMID- 30119099
TI  - ESPGHAN Distinguished Service Award 2018 to Professor Markku Maki.

PMID- 30119100
TI  - Use of Breast Milk and Other Feeding Practices Following Gastrointestinal Surgery
      in Infants.
AB  - OBJECTIVES: To characterize the enteral feeding practices in infants following
      gastrointestinal surgery. METHODS: We performed a retrospective analysis of
      infants who underwent intestinal surgery at age <6 months who survived to be fed
      enterally between January 2012-June 2017. Demographics, surgical characteristics,
      feeding practices, and growth-related outcomes during hospitalization, discharge,
      and follow-up (three-, six-, and twelve-months) were obtained from the electronic
      medical records. Descriptive statistics compared infants by their initial
      diagnosis. RESULTS: We reviewed 111 infants: necrotizing enterocolitis (NEC)=21,
      gastroschisis = 28, atresia = 27, spontaneous intestinal perforation (SIP) = 18,
      and Other diagnoses = 17. Most infants (77%) received mother's milk (MM) as the
      first post-operative feed, but this differed by diagnosis (p = 0.004). Donor milk
      was used in 11%, most commonly in infants with NEC and SIP. Infants with NEC were
      least likely to continue MM in the hospital (7%, P = 0.0014) and were more likely
      to receive elemental formula. Only 44% of infants received MM at discharge. After
      one year, 25% were fed MM. The majority of infants were discharged with feeding
      tubes (nasogastric: 35%, gastric: 23%). While all groups had acceptable weights
      at discharge, infants with NEC (Z-score: -1.8) and SIP (Z-score: -1.1) showed
      growth failure at three-months (Z-scores: -3.3, -3.2, respectively, P < 0.0001),
      but had appropriate gain by one year (Z-scores: -1.1, -1.7, respectively).
      CONCLUSIONS: Despite most infants receiving MM in the early post-operative
      period, <50% at discharge and only 25% at one-year still received MM. Weight gain
      after discharge in infants with NEC and SIP warrants close monitoring.

PMID- 30119101
TI  - Weight Gain Trajectory Predicts Long-Term Overweight and Obesity After Pediatric
      Liver Transplant.
AB  - OBJECTIVE: To identify early predictors of long-term overweight and obesity in
      pediatric liver transplant recipients. METHODS: Single-center, retrospective
      review of children who underwent liver transplant before age 6 years. Body Mass
      Index (BMI), weight, and height percentiles at transplant and post-transplant
      were calculated. BMI, weight gain trajectories, and failure-to-thrive (FTT) were
      examined as predictors of overweight/obesity at 3 and 5 years post-transplant.
      RESULTS: Children (n = 70) were median 0.9 years at transplant. Median BMI
      percentile increased from 37 (IQR 12-73) at transplant to 83 (IQR 64-97) at 12
      months, with median weight percentile 47 (IQR 26 - 67) and height percentile 9
      (IQR 2- 32). Overweight/obesity prevalence peaked at 3 years post-transplant
      (44%). Children who were overweight/obese at 3 years post-transplant were more
      likely to be overweight/obese at transplant, and at 6 and 12 months post
      transplant (OR: 9.4, p = 0.02, OR: 6.7 p = 0.013, OR: 6.4 p = 0.007,
      respectively). The prevalence of overweight/obesity decreased to 26% at 5 years.
      Rapid weight gain post-transplant did not predict overweight/obesity at 3 or 5
      years. Over 1/3 of children who were FTT at transplant were overweight/obese at 3
      or 5 years, but FTT at transplant did not increase later obesity risk.
      CONCLUSIONS: Most children gain weight rapidly after liver transplant. Nearly
      half of transplant recipients are overweight/obese at 3 years, but the prevalence
      decreases by 5 years. Those who become overweight/obese tend to do so within one
      year post-transplant, making this an important time to identify high-risk
      children and provide counseling.

PMID- 30119103
TI  - Erythematous Nodule on the Face of a Child: Answer.

PMID- 30119102
TI  - Pilomatrixoma: A Comprehensive Review of the Literature.
AB  - INTRODUCTION: Pilomatrixoma, also known as calcifying epithelioma of Malherbe, is
      a superficial benign skin tumor that arises from hair follicle matrix cells.
      Although pilomatrixomas are well-recognized lesions, clinically they are
      frequently misdiagnosed as other skin conditions. By reviewing all the literature
      over the past 10 years, the aims of this article are to analyze the cause,
      clinical presentation, management, and outcome of pilomatrixoma among children
      and adults to gain a more complete understanding of this lesion in today's
      clinical context. METHODS: A MEDLINE and EMBASE search was conducted from January
      2005 to February 2015 using a combination of the terms: "child," "childhood,"
      "adult," and keywords: "pilomatrixoma," "pilomatricoma," and "calcifying
      epithelioma of Malherbe." A total of 150 articles were reviewed. RESULTS: The
      lesions occurred most commonly in the first and second decades (mean age 16 years
      and 7 months). The commonest presentation was of an asymptomatic, firm, slowly
      growing, mobile nodule. Only 16% were accurately diagnosed on clinical
      examination. Imaging in the form of ultrasound, computed tomography, and magnetic
      resonance imaging has been reported. Pathological diagnosis was achieved through
      incision, punch, and shave biopsies. Pathological findings are discussed and
      summarized in this review. CONCLUSION: Pilomatrixomas are thought to arise from
      mutation in the Wnt pathway and has been linked to several genetic conditions. It
      is commonly misdiagnosed preoperatively; however, with better awareness of the
      lesion, it can be appropriately treated while avoiding unnecessary diagnostic
      tests. Complete surgical excision with clear margins is almost always curative.

PMID- 30119104
TI  - An Unusual Case of Dactylitis With Nail Unit Involvement: Answer.

PMID- 30119105
TI  - An Unusual Vesiculopustular Eruption: Answer.

PMID- 30119106
TI  - Functional interaction between human dorsal premotor cortex and the ipsilateral
      primary motor cortex for grasp plans: a dual-site TMS study.
AB  - Recent findings suggest that the dorsal premotor cortex (PMd), a cortical area in
      the dorsomedial pathway, is involved in grasp control. It is unclear, however,
      whether human PMd transfers grasp-related information to the primary motor cortex
      hand area (M1HAND) during action preparation. The present study tested whether
      ipsilateral cortico-cortical connections between PMd and M1HAND in the left
      hemisphere are modulated during grasp preparation. Ten participants performed
      object-directed grasps and reaches with the right hand. Functional connectivity
      between left PMd and ipsilateral M1HAND was probed with dual-site transcranial
      magnetic stimulation. We found that PMd-M1HAND functional interactions were
      facilitated selectively for the muscles involved in the preparation of the
      upcoming grasps. The PMd-M1HAND interaction was facilitated for first dorsal
      interosseous muscle for both precision grip and whole-hand grasps and for
      abductor digiti minimi muscle for whole-hand grasps. We conclude that human
      dorsomedial PMd-M1HAND circuit encodes handgrip formation during grasp
      preparation.

PMID- 30119107
TI  - Impact of Chronic Steroid Use on Plastic Surgery Outcomes: Analysis of 94,140
      Cases.
AB  - BACKGROUND: Chronic steroid use suppresses inflammation, edema, and autoimmunity,
      and delays wound healing. Using data from the American College of Surgeons
      National Surgical Quality Improvement Program, this study characterizes the risk
      of perioperative chronic steroid use for complications in plastic surgery cases.
      METHODS: A retrospective study was performed on 94,140 plastic surgery cases from
      the American College of Surgeons National Surgical Quality Improvement Program
      database for the years 2006 to 2015. CPT codes were used to categorize
      operations. Patients were separated into two cohorts based on chronic steroid use
      status. Univariate analysis was performed using chi-square, Fisher's exact, or
      Wilcoxon rank sum test. Logistic regression models were fitted to evaluate the
      association between chronic steroid use and postoperative complications. Total
      hospital length of stay was compared. Odds ratios were computed at the 95 percent
      confidence interval. RESULTS: Chronic steroid users were more likely to develop
      surgical complications (OR, 1.3; p = 0.0452) and medical complications (OR, 1.8;
      p = 0.0002) compared with nonusers. Among the 10 most frequent procedures
      performed on chronic steroid users, steroid use was a significant risk factor for
      postoperative complications after reduction mammaplasty (OR, 2.2; p = 0.001);
      delayed insertion of breast prosthesis following mastopexy or mastectomy or
      during reconstruction (OR, 2.2; p = 0.049); and in trunk muscle, myocutaneous, or
      fasciocutaneous flap surgery (OR, 7.2; p = 0.0029). CONCLUSION: With this
      information in hand, plastic surgeons will be better equipped to counsel patients
      and adequately design perioperative protocols for chronic steroid users. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30119108
TI  - Preclinical Experience Using a New Robotic System Created for Microsurgery.
AB  - BACKGROUND: Robotic assistance in microsurgery could enhance human precision and
      dexterity to improve clinical outcomes. Because no robotic device has been
      designed primarily for microsurgery, the authors developed a dedicated
      microsurgical robotic system. This preclinical study investigates whether
      microsurgical anastomosis can be successfully completed on silicone vessels using
      a prototype of this new robotic system, and compares outcomes of robot-assisted
      versus conventional microsurgery. METHODS: Three participants at different levels
      of microsurgical training completed 10 anastomoses by hand and 10 anastomoses
      with robotic assistance. Four blinded, experienced microsurgeons evaluated the
      quality of the microsurgical skills using a modified version of the Structured
      Assessment of Microsurgical Skills. Time to perform the anastomosis and adverse
      events were recorded. RESULTS: The total time to perform the anastomoses with and
      without robotic assistance decreased to 35.1 minutes and 12.5 minutes,
      respectively, during the study. The overall performance and indicative skill of
      the Structured Assessment of Microsurgical Skills improved with the conventional
      method (from 2.8 to 3.6 and from 2.6 to 3.7, respectively) and the robot-assisted
      method (from 2.3 to 3.0 and from 2.3 to 3.1, respectively). CONCLUSIONS: It is
      feasible to complete anastomotic microsurgery on silicone vessels using the
      MicroSure robotic system. In comparison with the conventional method, time to
      perform the anastomosis was longer and quality of microsurgical skills was lower
      in the robot-assisted group. However, the robot-assisted performance showed
      steeper learning curves for both surgical time and domains of microsurgical
      skills. The encouraging results indicate further development of the system and
      (pre)clinical trials.

PMID- 30119109
TI  - Donor-Site Morbidity and Functional Status following Medial Femoral Condyle Flap
      Harvest.
AB  - BACKGROUND: The medial femoral condyle free vascularized bone flap is a valuable
      alternative to other types of vascularized bone grafts. The donor-site morbidity
      and functional outcomes after flap harvest have not been fully appreciated. The
      authors report the postoperative outcomes and analyze the impact of increasing
      the size of the flap on knee donor-site morbidity. METHODS: A retrospective chart
      review of patients who underwent medial femoral condyle flap surgery between 2001
      and 2012 at their institution was performed. The size of the flap was stratified,
      based on the largest dimension, into three groups. Demographics, outcomes, and
      complications related to the flap donor site were recorded and analyzed.
      Subsequently, functional status was assessed by administering a validated
      condition-specific measure. A univariate logistic regression analysis was
      performed, and results were analyzed. RESULTS: A total of 75 patients were
      identified. Average age was 29.5 +/- 15.2 years. Average follow-up time was 13
      months. The overall complication rate was 18.6 percent. Paresthesia in the
      saphenous nerve distribution was the most common complication. Increasing the
      size of the flap resulted in a significant elevation in complication risk (p <
      0.05). A total of 47 patients completed the Lower Extremity Functional Scale
      questionnaire. The average Lower Extremity Functional Scale score was 72.12 +/-
      14.18. Fifty-one percent (n = 24) scored 80 points, indicating a normal level of
      function on average. CONCLUSIONS: The medial femoral condyle flap has overall
      acceptable donor-site morbidity, with a good level of function postoperatively.
      Larger flaps are associated with a greater number of complications. CLINICAL
      QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

PMID- 30119110
TI  - Introducing Knowledge Translation to Plastic Surgery: Turning Evidence into
      Practice.
AB  - Best evidence has no bearing on quality of life if it is not implemented in
      clinical practice. The authors introduce knowledge translation as a theoretical
      framework for closing the gap between evidence and practice in plastic surgery.
      The current state of published evidence in plastic surgery is reviewed and
      evaluated, with the recommendation to use the EQUATOR Network's guidelines for
      reporting clinical research findings. Tools and strategies are offered for the
      reader to understand and integrate evidence at the bedside. Systemic solutions
      are also proposed for the dissemination of best evidence to facilitate its
      translation into practice.

PMID- 30119111
TI  - Increasing Diversity in Plastic Surgery.

PMID- 30119112
TI  - Reply to "Lymphedema Quality of Life Score (LeQOLiS): A Simple Method for
      Evaluation of Subjective Symptoms in Extremity Lymphedema Patients".

PMID- 30119113
TI  - An Intraoperative Three-Dimensional Imaging System for Better Image Sharing and
      Protection of Reconstructive Surgeons' Neck.

PMID- 30119114
TI  - Reply: Reconstruction of the Heel, Middle Foot Sole, and Plantar Forefoot with
      the Medial Plantar Artery Perforator Flap: Clinical Experience with 28 Cases.

PMID- 30119115
TI  - Commentary to "Targeting Reflux-free Vein Using Indocyanine Green Dye
      Angiography".

PMID- 30119116
TI  - Reply: An Intraoperative 3D Imaging System for Better Image Sharing and
      Protection of Reconstructive Surgeons' Neck.

PMID- 30119118
TI  - Aesthetic Functional Surgery with ulnar artery perforator, an easier alternative
      to super-thin SCIP.

PMID- 30119117
TI  - Reply: Autologous Fat Injection versus Lundborg Resection Arthroplasty for the
      Treatment of Trapeziometacarpal Joint Osteoarthritis.

PMID- 30119119
TI  - Autologous Fat Injection versus Lundborg Resection Arthroplasty for the Treatment
      of Trapeziometacarpal Joint Osteoarthritis.

PMID- 30119120
TI  - Reply: Aesthetic Functional Surgery with proximal ulnar artery perforator, an
      easier alternative to super-thin SCIP.

PMID- 30119121
TI  - Vascular Anomalies: From a Clinicohistologic to a Genetic Framework.

PMID- 30119122
TI  - Reply: Increasing Diversity in Plastic Surgery.

PMID- 30119123
TI  - Lymphedema Quality of Life Score (LeQOLiS): A Simple Method for Evaluation of
      Subjective Symptoms in Extremity Lymphedema Patients.

PMID- 30119124
TI  - Three-Dimensional Reconstruction: The Waveform Design of Free Perforator Flap for
      the Heel Defect Repair.

PMID- 30119126
TI  - A New Simple Maneuver to Manipulate Sutures during Microvascular Anastomosis
      Using Microsuction.

PMID- 30119125
TI  - Endoscopic Nipple-Sparing Mastectomy with Immediate Multistage Fat Grafting for
      Total Breast Reconstruction: A New Combination for Minimal Scar Breast Cancer
      Surgery.

PMID- 30119127
TI  - Coned Radial Forearm Free Flap for Improved Retention of Orbital Prosthesis
      following Orbital Exenteration.

PMID- 30119128
TI  - The Fourth Industrial Revolution Tackles Plastic Surgeons.

PMID- 30119129
TI  - Systematic Review of the Cost of Applying to Integrated Plastic Surgery
      Residency.

PMID- 30119130
TI  - High-Throughput Screening of Full-Face Clinically Relevant Arterial Variations
      Using Three-Dimensional Postmortem Computed Tomography.
AB  - BACKGROUND: Vascular complications resulting from intravascular filler injection
      and embolism are major safety concerns for facial filler injection. It is
      essential to systematically screen full-face arterial variations and help design
      evidence-based safe filler injection protocols. METHODS: The carotid arteries of
      22 cadaveric heads were infused with adequate lead oxide contrast. The facial and
      superficial temporal arteries of another 12 cadaveric heads were injected with
      the contrast in a sequential order. A computed tomographic scan was acquired
      after each contrast injection, and each three-dimensional computed tomographic
      scan was reconstructed using validated algorithms. RESULTS: Three-dimensional
      computed tomography clearly demonstrated the course, relative depth, and
      anastomosis of all major arteries in 63 qualified hemifaces. The ophthalmic
      angiosome consistently deploys two distinctive layers of branch arteries to the
      forehead. The superficial temporal and superior palpebral arteries run along the
      preauricular and superior palpebral creases, respectively. The study found that
      74.6 percent of the hemifaces had nasolabial trunks coursing along the nasolabial
      crease, and that 50.8 percent of the hemifaces had infraorbital trunks that ran
      through the infraorbital region. Fifty percent of the angular arteries were the
      direct anastomotic channels between the facial and ophthalmic angiosomes, and
      29.2 percent of the angular arteries were members of the ophthalmic angiosomes.
      CONCLUSIONS: Full-face arterial variations were mapped using postmortem three
      dimensional computed tomography. Facial creases were in general correlated with
      underlying deep arteries. Facial and angular artery variations were identified at
      high resolution, and reclassified into clinically relevant types to guide medical
      practice.

PMID- 30119131
TI  - Plumbagin inhibits the proliferation of nasopharyngeal carcinoma 6-10B cells by
      upregulation of reactive oxygen species.
AB  - Plumbagin (PLB) is the primary component of the traditional Chinese medicine
      Baihua Dan, and possesses anti-infection and anticancer effects, with the ability
      to enhance the sensitivity of tumor cells to radiation therapy. However, the
      anticancer effect of PLB on nasopharyngeal carcinoma and the underlying
      mechanisms remain unclear. In this study, we investigated the anticancer effects
      of PLB on nasopharyngeal carcinoma 6-10B cells and clarified its molecular
      mechanisms in vitro. The results showed that PLB was effective against 6-10B
      cells proliferation in a dose-dependent manner by inducing G2/M phase cell cycle
      arrest. Furthermore, our data showed that PLB induced reactive oxygen species
      accumulation, which inhibited the GSK3beta/STAT3 pathway and arrested the G2/M
      phase. Therefore, our results provided new insight into the mechanism of the
      antitumor effects of PLB, supporting PLB as a prospective therapeutic drug in
      nasopharyngeal carcinoma by modulating intracellular redox balance.

PMID- 30119132
TI  - Genetic polymorphisms in candidate genes are not associated with increased
      vincristine-related peripheral neuropathy in Arab children treated for acute
      childhood leukemia: a single institution study.
AB  - OBJECTIVE: The aim of this study was to evaluate the potential association
      between candidate genetic polymorphisms and vincristine-related peripheral
      neuropathy in Arab children with acute lymphoblastic leukemia (ALL). PATIENTS AND
      METHODS: This is a retrospective evaluation of 133 Arab children treated for ALL
      at the Children's Cancer Center of Lebanon. Incidence and severity of, as well as
      the timing (in weeks) at which grade 2 or higher peripheral neuropathy occurred
      were recorded. Genotyping for ABCB1 (rs1045642), ABCB1 (rs1128503), ABCC2
      (rs717620), CEP72 (rs924607), ETAA1 (rs17032980), and MTNR1B (rs12786200) was
      performed. RESULTS: A total of 26 (19.5%) individuals developed peripheral
      neuropathy, three of which occurred during the induction phase. No statistically
      significant associations were revealed for any of the polymorphisms with either
      incidence of vincristine-related toxicity, toxicity severity, or time to the
      first episode of grade 2 or higher vincristine-related peripheral neuropathy.
      CONCLUSION: This study presents the first pharmacogenetic analysis of vincristine
      related peripheral neuropathy in children with ALL in an Arab country. We have
      shown that genetic polymorphisms in candidate genes are not associated with
      peripheral neuropathy secondary to chronic therapy with high-dose vincristine (2
      mg/m) during the continuation phase. Concerning CEP72, our results are in line
      with the findings from the St Jude cohort of children treated for ALL with higher
      vincristine doses during chronic treatment. Larger high-throughput genetic
      analyses may be warranted to evaluate variants in other candidate genes such as
      CYP3A5 and reveal new nonpreviously reported alleles that may be peculiar to this
      region of the world.

PMID- 30119133
TI  - Inflammatory Response 24 h Post-Exercise in Youth with Juvenile Idiopathic
      Arthritis.
AB  - The aim of this study was to measure the impact, at 24 h post-exercise, of a
      single exercise bout on plasma inflammatory markers such as calprotectin, IL-6,
      sIL-6 R, sgp130 and the hypothalamic-pituitary-adrenal (HPA) axis in children
      with juvenile idiopathic arthritis (JIA).Twelve children with JIA attended the
      laboratory on three consecutive days (control day, exercise day and 24 h post
      exercise), including a 20-min exercise bout on a cycle-ergometer at 70% of max.
      HR at 8:30 a.m. on day 2. Plasma concentrations of calprotectin, IL-6, sIL-6 R,
      sgp130, cortisol, ACTH and DHEA were measured on venous blood samples taken every
      day.at rest and at 8:30, 8:50, 9:30, 10:30 a.m. and 12:00, 3:00, 5:30 p.m.A
      single exercise bout increased plasma calprotectin 1.7-fold (p<0.001) but did not
      increase IL-6 and soluble IL-6 receptors in short-term post-exercise recovery.
      However, at 24 h post-exercise, calprotectin, IL-6 and its receptors had
      decreased compared to control-day levels. There was a transient 2-fold increase
      in post-exercise self-evaluated pain (p=0.03) that disappeared in the evening
      without repercussions the following day.Physical activity in children with JIA
      results in a slight transient systemic inflammation but seems to be followed by
      counter-regulation at 24 h post-exercise with a decrease in proinflammatory
      markers.

PMID- 30119134
TI  - Ankle Joint Control in People with Chronic Ankle Instability During Run-and-cut
      Movements.
AB  - Despite a considerable amount of research, the deficits causing recurrent sprains
      in people with chronic ankle instability are still unclear. Changes in frontal
      plane kinematics and decreased peroneal activation have been proposed as
      potential underlying mechanisms, but whether people with ankle instability show
      deficits in control of injury-relevant movements is not well understood.
      Therefore, the purpose of the present study was to analyse ankle joint kinematics
      and kinetics as well as neuromuscular activation during dynamic change-of
      direction movements. Eighteen participants with functional instability, 18
      participants with functional and mechanical instability and 18 healthy controls
      performed 45 degrees  sidestep-cutting and 180 degrees  turning movements in
      reaction to light signals. During sidestep-cutting both instability groups
      displayed significantly lower inversion angles than controls when the trials with
      the highest maximum inversion angle of each participant were compared. In turning
      movements, participants with functional instability presented significantly lower
      average maximum inversion angles than controls as well as higher peroneal
      activation before foot strike than participants with both functional and
      mechanical instability. We theorize that the observed changes in movement
      kinematics of participants with chronic ankle instability are the result of a
      protective strategy to limit frontal plane ankle joint loading in potentially
      harmful situations.

PMID- 30119135
TI  - Differential Expression of MicroRNAs and miR-206-Mediated Downregulation of BDNF
      Expression in the Rat Fetal Brain Following Maternal Hypothyroidism.
AB  - To investigate the mechanism responsible for the neurological alterations, miRNA
      expression profile and brain-derived neurotrophic factor (BDNF) were evaluated in
      brain tissues of fetal or neonatal rats and from maternal rats with
      hypothyroidism. Ninety female Wistar rats were divided into a control and a
      hypothyroid group, which were mated. Brain samples of the offspring were obtained
      at maternal embryonic day (E) E13 and E17 as well as postnatal day (P) P0 and P7,
      and the hippocampus and cortex were separated at P7. BDNF mRNA at E13 was tested
      by real-time PCR and protein expression by Western blot. Luciferase assays were
      used to confirm that miR-206 targets the 3'-untranslated region (3'-UTR) of BDNF.
      In the brain tissues of fetal and neonatal rats from maternal rats with
      hypothyroidism, differentiation miRNAs profile were found at E13, E17, P0, and
      P7. Compared with the control group, miR-206 levels in the hypothyroidism group
      were increased by 3.1-fold by micro-array, and were higher as measured by SYBR
      green real-time qRT-PCR (p<0.01). There was no significant difference in the BDNF
      mRNA levels at E13 between the hypothyroidism group and the control group
      (1.767+/-0.477 vs. 1.798+/-0.462, respectively; p>0.05), but pro-BDNF and mature
      BDNF protein levels in the hypothyroid group at E13 were significantly lower than
      those in the control group (p<0.05). miR-206 targeted 3'-UTR of BDNF. Our data
      highlight the role of miR-206 as a post-transcriptional inhibitor of BDNF at E13
      in pregnant hypothyroid rats.

PMID- 30119136
TI  - Cardiorespiratory Fitness is Associated with Glycated Hemoglobin and Triglyceride
      Levels in Severely Obese Men: A Retrospective Clinical Data Analysis.
AB  - BACKGROUND: Even subjects with severe obesity show a wide range of metabolic
      health states, with some showing marked alterations in glucose and lipid
      metabolism whereas others do not. In severely obese women, we could recently show
      that the degree of cardiorespiratory fitness is, independently of body mass and
      age, associated with several markers of glucose and lipid metabolism. AIMS: In
      our retrospective study on a clinical data set, we questioned whether such an
      association also exists in severely obese men. METHODS: Cardiorespiratory
      fitness, i. e. workload (Wpeak) and oxygen uptake (VO2,peak) at peak exercise,
      was assessed by a bicycle spiroergometry in 133 severely obese men (all BMI>35 kg
      m-2). The following metabolic blood markers were also measured: Fasting serum
      glucose, insulin, triglycerides (TG), total, low-, high-density cholesterol
      (Chol, LDL, HDL), uric acid, and whole blood glycated hemoglobin (HbA1c). The
      Chol/HDL ratio and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
      were also calculated. RESULTS: Multiple stepwise linear regression models
      including age, body mass, and smoking status as independent variables revealed
      that Wpeak and VO2,peak, explained 4.5 to 10.7% of variance in HbA1c and TG (all
      beta<- 0.22; all p<0.02). Including fat free mass instead of body mass in
      respective models revealed that both Wpeak and VO2,peak were predictors of HbA1c
      and TG (all beta<- 0.265; all p<0.013), respectively, while Wpeak also accounted
      for variance in glucose and Chol (both beta<- 0.259; both p<0.023). CONCLUSIONS:
      Similar to previous observations in women, our data indicate that
      cardiorespiratory fitness assessed by bicycle ergospirometry test is associated
      with glucose and lipid metabolism in severely obese men. The strength of the
      found associations suggest a mild to moderate influence of cardiorespiratory
      fitness on metabolic health in severe obesity.

PMID- 30119137
TI  - T2 Magnetic Resonance to Monitor Hemostasis.
AB  - There is a clinical need for pragmatic approaches to measure integrated
      hemostatic reactions in whole blood rapidly, using small volumes of blood. The
      authors have applied T2 magnetic resonance (T2MR) to assess coagulation reactions
      based on partitioning of red blood cells and proteins that occurs during fibrin
      formation and platelet-mediated clot contraction. T2MR is amenable to measuring
      clotting times, individual coagulation factors, and platelet function. T2MR also
      revealed a novel "hypercoagulable" signature characterized by fibrin clots almost
      insusceptible to fibrinolysis that surround tessellated arrays of polyhedral
      erythrocytes ("third peak"). This signature, which develops under conditions
      associated with intense clot formation in vitro, may help identify patients at
      risk of developing thrombosis and for monitoring antithrombotic therapies in the
      future.

PMID- 30119138
TI  - Prothrombotic State Induced by Middle-Distance Endurance Exercise in Middle-Aged
      Athletes.
AB  - Since the impact of possible prothrombotic factors on blood coagulation resulting
      from exercise remains elusive, this study investigated the acute effects of
      middle-distance endurance running on blood coagulation parameters in middle-aged
      athletes. The study population consisted of 33 male endurance runners who were
      engaged in a 21.1 km run under competitive conditions. Blood samples were
      collected before the run, immediately after the run, and 3 hours after run
      completion. Samples were assessed for activated partial thromboplastin time
      (APTT), prothrombin time (PT), fibrinogen, D-dimer, factor VIII (FVIII), von
      Willebrand factor antigen (VWF:Ag), endogenous thrombin potential (area under the
      curve of thrombin generation [TGA-AUC]), and peak thrombin generation (TGA-PK).
      Post-run variations were expressed as delta (Delta). At baseline, APTT was found
      to be significantly associated with ABO blood group, VWF:Ag, and FVIII;
      fibrinogen with age; VWF:Ag with BMI, training regimen, and ABO blood group; APTT
      with FVIII; FVIII with VWF:Ag and ABO blood group; APTT with VWF:Ag; and TGA-PK
      with ABO blood group, PT, and TGA-AUC. Immediately after the run, statistically
      significant increases were observed for PT, D-dimer, VWF:Ag, and FVIII, while
      statistically significant reductions could be observed for APTT, TGA-AUC, and TGA
      PK. Fibrinogen values remained unchanged. Significant correlations were observed
      between Delta VWF:Ag and Delta FVIII, Delta APTT and Delta VWF:Ag, Delta APTT and
      Delta FVIII, Delta TGA-AUC and Delta TGA-PK, and between Delta D-dimer and Delta
      TGA-AUC and Delta TGA-PK. No Delta variation was associated with running time.
      The results of this study seemingly suggest that middle-distance competitive
      running may evoke several prothrombotic changes in blood coagulation.

PMID- 30119139
TI  - Atrial Fibrillation and Malignancy: The Clinical Performance of Non-Vitamin K
      Oral Anticoagulants-A Systematic Review.
AB  - Atrial fibrillation (AF) is commonly diagnosed in the setting of active cancer.
      Because of an increased risk of either thromboembolic events or bleeding, the
      decision to initiate therapeutic anticoagulation in patients with active cancer
      can be challenging. Moreover, little is still known about the optimal
      anticoagulation therapy in the setting of AF and cancer, and no guidelines are as
      yet available. Considering that nonvitamin K antagonist oral anticoagulants
      (NOACs) are recommended as alternatives to vitamin K antagonists for stroke
      prevention in AF patients with CHA2DS2-VASc score >=2, the authors performed a
      systematic review of the current literature to describe the efficacy and safety
      of NOACs in AF patients with malignancy.

PMID- 30119140
TI  - No evidence of overweight in long-term survivors of childhood cancer after
      glucocorticoid treatment.
AB  - BACKGROUND: Glucocorticoids can lead to weight gain during cancer treatment, but
      to the authors' knowledge, little is known regarding their long-term effects in
      childhood cancer survivors (CCS). METHODS: As part of the Swiss Childhood Cancer
      Survivor Study, the authors sent a questionnaire to CCS aged <21 years at
      diagnosis who were residing in Switzerland, had survived >=5 years, and were aged
      15 to 45 years at the time of the survey. Cumulative doses of glucocorticoids
      were assessed from medical records and study protocols and body mass index was
      calculated from self-reported height and weight at the time of the survey. The
      authors compared the prevalence of overweight between CCS, their siblings, and
      the general population (Swiss Health Survey [SHS]) and investigated the
      association between overweight and treatment-related risk factors using
      multivariable logistic regression. RESULTS: The study included 1936 CCS, 546
      siblings, and 9591 SHS participants. The median age of the CCS at the time of the
      survey was 24 years (interquartile range, 20-31 years) and the median time since
      diagnosis was 17 years (interquartile range, 12-22 years). At the time of the
      survey, approximately 26% of CCS were overweight, a percentage that was
      comparable to that among siblings (24%) and the SHS participants (25%). The
      prevalence of overweight was 24% in CCS treated with glucocorticoids only (686
      CCS), 37% in those treated with cranial radiotherapy (CRT) (127 CCS), and 49% in
      those who received treatment with both glucocorticoids and CRT (101 CCS) (P <
      .001). The authors found no evidence of a dose-response relationship between
      cumulative glucocorticoid doses and overweight and no evidence that CRT modified
      the effect of the cumulative glucocorticoid dose on overweight. CONCLUSIONS: The
      results of the current study suggest that glucocorticoids used for the treatment
      of childhood cancer are not associated with long-term risk of overweight.

PMID- 30119141
TI  - C-reactive protein/albumin ratio is a poor prognostic factor of esophagogastric
      junction and upper gastric cancer.
AB  - BACKGROUND AND AIM: The C-reactive protein (CRP)/albumin (Alb) ratio has been
      reported as a novel prognostic marker in several cancers. The objective of this
      study was to investigate the prognostic value of the CRP/Alb ratio in patients
      who underwent surgery for adenocarcinoma of the esophagogastric junction (AEG)
      and upper gastric cancer (UGC). METHODS: Data for 144 patients who underwent
      surgery for AEG and UGC were reviewed. The CRP/Alb ratio, neutrophil-lymphocyte
      ratio, platelet-lymphocyte ratio, Glasgow Prognostic Score, and controlling
      nutritional status score were calculated, and the relationship between these
      biomarkers and postoperative prognosis was analyzed. RESULTS: The optimal cutoff
      value of the CRP/Alb ratio was determined to be 0.1. According to the cutoff
      value of CRP/Alb ratio, patients were divided into two groups (CRP/Alb < 0.1, n =
      124; CRP/Alb >= 0.1, n = 20). The 5-year recurrence-free survival and overall
      survival (OS) rates were significantly lower in the patients with the CRP/Alb
      ratio >= 0.1 than in those with the CRP/Alb ratio < 0.1 (recurrence-free
      survival: 44.9% vs 77.9%, P = 0.0011; OS: 43.4% vs 82.0%, P < 0.0001). In the
      multivariate analyses, the N-stage, and CRP/Alb ratio >= 0.1 were identified as
      independent predictive factors for OS in patients with AEG and UGC (P = 0.0061
      and P = 0.0439, respectively). CONCLUSIONS: The CRP/Alb ratio was strongly
      associated with poor prognosis in patients who underwent surgery for AEG and UGC.

PMID- 30119142
TI  - Development and validation of a UPLC-MS/MS method for quantification of
      osimertinib (AZD9291) and its metabolite AZ5104 in human plasma.
AB  - Osimertinib (AZD9291) is a highly selective irreversible epidermal growth factor
      receptor tyrosine kinase inhibitor (EGFR TKI) designed to treat nonsmall-cell
      lung cancer patients with EGFR active and T790 M resistant mutations. A rapid and
      sensitive method for quantitative analysis by ultra-performance liquid
      chromatography-tandem mass spectrometry of osimertinib and its metabolite AZ5104
      in human plasma was developed and validated. The samples were prepared by protein
      precipitation and separated on a BEH C18 column (2.1 * 50 mm, 1.7 MUm) by
      gradient elution with 0.1% (v/v) formic acid and 10 mm ammonium acetate in water
      and acetonitrile as the mobile phase. Electrospray ionization in positive ion
      mode and multiple reaction monitoring were used to monitor the ion transitions at
      m/z 500.4 -> 385.3 and 486.3 -> 371.1. The results indicated that the method had
      excellent sensitivity and specificity. The validation was performed in a range
      from 0.5 to 100 ng/mL. Intra-day and inter-day precisions (in terms of RSD) were
      all <15%, and the accuracies (in terms of RE) were within +/-15%. The lower limit
      of quantification, matrix effect, extraction recovery, stability and dilution
      integrity were also validated and satisfied the validation criteria. Finally,
      this method was successfully applied in a retrospective analysis, and the predose
      samples of 52 nonsmall-cell lung cancer patients who were enrolled in a novel
      third EGFR TKI clinical trial were analyzed for screening regardless of whether
      they had previously received osimertinib treatments.

PMID- 30119143
TI  - In vitro and in vivo evaluation of a posaconazole-sulfobutyl ether-beta
      cyclodextrin inclusion complex.
AB  - Posaconazole (PCZ) is a triazole antifungal agent with an extended spectrum of
      antifungal activity. It is approved for the prophylaxis of invasive fungal
      infections in patients with neutropenia or in hematopoietic stem cell transplant
      recipients undergoing high-dose immunosuppressive therapy for graft-vs-host
      disease, and for the treatment of fungal infections. However, its pharmacological
      effects are severely limited owing to its poor solubility and low
      bioavailability. In order to solve these problems, a sulfobutyl ether-beta
      cyclodextrin compound was used to prepare an intramuscular injection to improve
      the bioavailability of posaconazole. The extracorporeal dissolution rate of
      posaconazole was markedly improved by this inclusion complex with >90% being
      released within 5 min, and the in vivo pharmacokinetics were studied using a
      HPLC/MS/MS method for quantifying posaconazole and the posaconazole-sulfobutyl
      ether-beta-cyclodextrin inclusion complex in rat blood. Posaconazole and an
      internal standard, itraconazole, were extracted by protein precipitation using
      acetonitrile. The concentration range of posaconazole was 0.05-4.0 MUg/mL with
      good linearity (r = 0.9980), the peak concentrations of pure posaconazole and the
      inclusion complex were 0.565 +/- 0.102 MUg/mL and 1.12 +/- 0.091 MUg/mL, the
      values for AUC0-t were 12.2 +/- 2.5 and 19.9 +/- 2.5 MUg h/mL, and the values for
      AUC0-infinity were 16.4 +/- 3.2 and 25.0 +/- 3.5 MUg h/mL, respectively. The main
      pharmacokinetics parameters showed significant differences (P < 0.01). Compared
      with pure posaconazole, the posaconazole-sulfobutyl ether-beta-cyclodextrin
      inclusion complex markedly improved the bioavailability of posaconazole.

PMID- 30119144
TI  - Financial Instruments for Mitigation of Flood Risks: The Case of Florence.
AB  - This article analyzes the mechanisms and effects of innovative financial
      instruments that a central public administration (CPA) may adopt to minimize the
      flood risk in particularly exposed regions. The pattern we suggest assumes that
      in risky areas the CPA can issue two financial instruments, called project
      options and CAT-bonds, producing a dynamic interaction among three types of
      agents: the CPA itself, the local public administrations, and private investors.
      We explore the possible scenarios of such interaction and the conditions under
      which the CPA's goal of maximal risk reduction is attained. This pattern is
      proposed for flood risk mitigation in the city of Florence, where the model
      dynamics are tested assuming parameters obtained from engineering studies.

PMID- 30119145
TI  - Effects of epidural morphine and levobupivacaine combination before incision and
      after incision and in the postoperative period on thoracotomy pain and stress
      response
AB  - Background/aim: This study aims to investigate the effects of thoracic epidural
      analgesia, before and after surgical incision and in the postoperative period, on
      thoracotomy pain and stress response. Materials and methods: A  total  of  45 
      patients  who  were  scheduled  for  posterolateral  thoracotomy  were  included 
      in  this  study.  A  combination  of  epidural  levobupivacaine  and  morphine 
      was  administered  as  a  bolus  before  incision  (Group  1;  n=15),  after 
      incision  (Group 2; n=15), or at the end of surgery (Group 3; n=15).
      Additionally, infusion was used in Group 1 and Group 2 during operation.
      Postoperative patient-controlled epidural analgesia infusion pumps were connected
      to all patients. Visual analog scale (VAS) scores and morphine  consumption  were
      recorded  during  the  postoperative  48  h.  Glucose,  insulin,  cortisol,  and
      C-reactive  protein  (CRP)  levels  were compared before surgery and at 4, 24,
      and 48 h after the operation. Results: There were no differences in the morphine
      consumption and VAS scores for all measurements among the groups (P > 0.05). Both
      blood glucose levels at 4 h and CRP values at 48 h were higher in Group 2 than
      Group 1 (P < 0.05). Cortisol levels at 4, 24, and 48 h after the operation were
      similar to baseline values in all groups (P > 0.05). Conclusion: The application
      of thoracic epidural analgesia before and after surgical incision and in the
      postoperative period did not result  in  a  significant  difference  in  the 
      severity  of  the  postthoracotomy  pain  and  stress  response  in  all  groups.
      Based  on  our  results,  we suggest that epidural levobupivacaine combined with
      morphine provides an effective and safe analgesia and can partially suppress
      surgical stress response.

PMID- 30119146
TI  - Relationship of serum HLA-B alleles and TNF-alpha with rheumatic heart disease
AB  - Background/aim: Acute  rheumatic  fever  and  rheumatic  heart  disease  are 
      major  causes  of  morbidity  and  mortality  in  developing  countries. Genetic
      studies have determined that the immune response in rheumatic heart disease is
      genetically controlled and that there is a close relationship between the gene of
      concern and the class II human leukocyte antigen (HLA) gene. The aim of this
      study was to evaluate the relationship of serum HLA-B alleles and tumor necrosis
      factor alpha (TNF-alpha) with rheumatic heart disease. Materials and methods: A
      total of 50 consecutive patients with rheumatic heart disease and 50 controls
      were enrolled in the study. HLA alleles were analyzed using sequence-specific
      primer-polymerase chain reaction and nucleotide sequencing. Results: The  HLA-B35
      allele  was  significantly  more  common  in  patients  with  rheumatic  heart 
      disease  than  the  control  group  (P  =  0.043). The HLA-B44 allele was
      significantly more common in control patients than in patients with rheumatic
      heart disease (P = 0.014). There was a significant inverse correlation between
      high-sensitivity C-reactive protein and mitral valve area (P = 0.001). There was
      no correlation between TNF-alpha levels and mitral valve area (P = 0.066).
      Conclusion: Our findings confirmed the association between HLA-B alleles and
      rheumatic heart disease.

PMID- 30119147
TI  - Antibiotic treatment outcomes in community-acquired pneumonia
AB  - Background/aim: The optimal empiric antibiotic regimen for patients with
      community-acquired pneumonia (CAP) remains unclear. This  study  aimed  to 
      evaluate  the  clinical  cure  rate,  mortality,  and  length  of  stay  among 
      patients  hospitalized  with  community-acquired  pneumonia  in  nonintensive 
      care  unit  (ICU)  wards  and  treated  with  a  beta-lactam,  beta-lactam  and 
      macrolide  combination,  or  a  fluoroquinolone. Materials and methods: This
      prospective cohort study was performed using standardized web-based database
      sheets from January 2009 to September 2013 in nine tertiary care hospitals in
      Turkey. Results: Six hundred and twenty-one consecutive patients were enrolled. A
      pathogen was identified in 78 (12.6%) patients. The most frequently isolated
      bacteria were S. pneumoniae (21.8%) and P. aeruginosa (19.2%). The clinical cure
      rate and length of stay were not different among patients treated with beta
      lactam, beta-lactam and macrolide combination, and fluoroquinolone. Forty-seven
      patients (9.2%) died during the hospitalization period. There was no difference
      in survival among the three treatment groups. Conclusion: In patients admitted to
      non-ICU hospital wards for CAP, there was no difference in clinical outcomes
      between beta-lactam, beta-lactam and macrolide combination, and fluoroquinolone
      regimens.

PMID- 30119148
TI  - Effect of intraoperative infusion of sufentanil versus remifentanil on
      postoperative shivering in Korea: a prospective, double-blinded, randomized
      control study
AB  - Background/aim: The number of published papers that compare the incidence of
      sufentanil- and remifentanil-related postoperative shivering is insufficient. We
      investigated the incidence of postoperative shivering after total intravenous
      anesthesia with either sufentanil or remifentanil in patients who underwent
      elective surgery. Materials and methods: Eighty-three patients, with a physical
      status classified as American Society of Anesthesiologists I or II, were randomly
      allocated to either the remifentanil-propofol (RP group, n = 40) or sufentanil
      propofol (SP group, n = 43) group. The primary endpoint was the incidence of
      postoperative shivering 1 h after entering the recovery room. The secondary
      endpoints were intraoperative core temperatures of the esophagus and tympanic
      membrane at 30 min after the induction of anesthesia and at the end of surgery.
      Results: The  overall  postoperative  shivering  incidence  was  not 
      significantly  different  between  the  RP  (15%)  and  SP  (11.6%)  groups  (P =
      0.651). The intraoperative temperatures and their changes (the temperature 30 min
      after induction minus that after surgery) as measured at the distal esophagus and
      tympanic membrane were not significantly different between the RP and SP groups.
      Conclusion: The incidence of postoperative shivering related to sufentanil was
      less than that related to remifentanil, with no significant differences in the
      intraoperative core temperatures.

PMID- 30119149
TI  - Predictors of mortality in cancer patients who needintensive  care unit support:
      a two center cohort study
AB  - Background/aim: Cancer patients frequently need intensive care support due to
      respiratory failure. We aimed to evaluate the predictors of mortality in cancer
      patients who were admitted to the intensive care unit (ICU). Materials and
      methods: This  study  was  performed  in  the  ICUs  of  two  centers  between  1
      January  2008  and  31  December  2015.  Demographic data, cancer type, causes
      of respiratory failure, comorbidities, APACHE II scores, treatments, and
      mortality rates were recorded. Results: A total number of 583 cancer patients
      (477 males) were enrolled from the two centers. Of those, 472 patients had lung
      cancer (81%),  while  111  had  extrapulmonary  malignancies  (19%),  having 
      similar  mortality  rates.  Causes  of  respiratory  failure  were  mostly 
      invasion of the cancer itself in 84% of cases and due to infection in 12%. ICU
      mortality rate was 53% and the 1-year mortality rate was 80%. APACHE II scores
      were significantly higher in nonsurvivors (P < 0.001). One-year survival was
      found to be significantly shorter in females than males (9 days vs. 12 days) in
      patients with lung cancer. Conclusion: Mortality rates of cancer patients who
      need ICU support are higher than overall ICU mortality. High APACHE II scores and
      female sex seem to be related to mortality in these patients.

PMID- 30119150
TI  - Cytoplasmic abnormalities of mature oocytes have a significant effect on
      fertilization in Bologna poor responders
AB  - Background/aim: We  aimed  to  investigate  whether  oocyte  morphologic 
      abnormalities  affected  cycle  outcome  in  poor  responder  infertile women who
      fulfilled the Bologna criteria. Materials and methods: Data  were  obtained  from
      infertile  couples  who  underwent    ICSI  and  embryo  transfer  at  the 
      Zeynep  Kamil  Maternity and Children's Health Training and Research Hospital
      Assisted Reproduction Unit in Istanbul, Turkey. They were allocated to two
      groups: Group A, poor responders, and Group B, normal responders. All
      morphological abnormalities of oocytes retrieved were reviewed  and  grouped  as 
      cytoplasmic  abnormalities  or  extracytoplasmic  abnormalities.  All 
      morphological  features  were  compared  between  the  poor  and  normal 
      responder  groups.  ICSI  cycle  outcomes  were  described  as  biochemical 
      pregnancy,  fertilization  rate,  number of top-quality zygotes, top-quality
      zygote rate, number of embryos transferred, and number of top-quality embryos
      transferred. The relation between each morphological feature and ICSI outcomes
      was investigated in each group. Results: The  results  showed  no  difference 
      between  the  groups  in  terms  of  morphological  features  of  oocytes.  The 
      relation  between  ICSI  cycle  outcomes  and  each  oocyte  morphological 
      feature  was  compared  in  the  poor  and  normal  responder  groups.  Presence 
      of  cytoplasmic morphological abnormality was found to significantly correlate
      with the fertilization rate (P = 0.019) in poor responders. Conclusion: Our data
      show that oocyte cytoplasmic abnormalities significantly reduce fertilization
      achievement in poor responders.

PMID- 30119151
TI  - Detection of CCND1, C-MYC, and FGFR1 amplification using modified SYBR Green qPCR
      and FISH in breast cancer
AB  - Background/aim: The  aims  of  this  study  were  to  detect  CCND1, C-MYC,  and 
      FGFR1  amplification  using  qPCR,  confirmation  with  FISH, and to further
      assess their clinicopathological relevance. Materials and methods: Thirty-five
      breast tumor samples were analyzed for amplification of the selected genes using
      modified SYBR Green qPCR. The accuracy of the qPCR was assessed by FISH as a gold
      standard method. Results: CCND1, C-MYC,  and  FGFR1 amplifications  were 
      observed  in  34.28%,  28.57%,  and  17.14%  of  the  35  samples, 
      respectively.qPCR results were significantly confirmed by FISH and qPCR and FISH
      showed excellent correlation (P = 0.000). CCND1 amplification with tumor stage (P
      = 0.044), positive metastatic status (P = 0.042), positive family history (P =
      0.042), and C-MYC status (P = 0.005); C-MYC amplification with tumor size (P =
      0.021), tumor grade (P = 0.018), tumor stage (P = 0.032), and FGFR1 status (P <
      0.000); and FGFR1 amplification with tumor size (P = 0.041) and positive ER
      status (P = 0.042) were statistically associated. Conclusion: Our  findings 
      revealed  that  the  applied  qPCR  approach  could  precisely  quantify  the 
      relative  gene  copy  number.  More  studies with a larger sample size are
      suggested to confirm the clinicopathological value of CCND1, C-MYC, and FGFR1
      amplification.

PMID- 30119152
TI  - Effects of volume-controlled equal ratio ventilation with recruitment maneuver
      and positive end-expiratory pressure in laparoscopic sleeve gastrectomy: a
      prospective, randomized, controlled trial
AB  - Background/aim: We compared the effects of volume-controlled equal ratio
      ventilation (VC-ERV) and volume-controlled conventional ratio ventilation (VC
      CRV) on oxygenation, ventilation, respiratory mechanics, and hemodynamic status
      during mechanical ventilation with recruitment maneuver (RM) and positive end
      expiratory pressure (PEEP) in patients undergoing laparoscopic sleeve
      gastrectomy. Materials and methods: A  total  of  111  patients  scheduled  for 
      laparoscopic  sleeve  gastrectomy  were  randomized  to  ventilation  with 
      inspiratory to expiratory ratio of 1:1 (Group VC-ERV) or 1:2 (Group VC-CRV)
      following tracheal intubation. RM (40 cmH2O, 15 s) and PEEP (10 cmH2O) were
      administered to all patients. Arterial blood gas samples were taken and peak
      airway pressure (Ppeak), mean airway pressure (Pmean), dynamic compliance (Cdyn),
      mean arterial pressure, heart rate, SpO2, and EtCO2 were recorded at 4 time
      points. Postoperative respiratory complications were recorded. Results:
      Oxygenation,  ventilation,  Pmean  levels,  and  hemodynamic  variables  were 
      similar  in  both  groups.  VC-ERV  significantly  decreased Ppeak and increased
      Cdyn compared to VC-CRV at all time points of the operation (P < 0.05). No
      pulmonary complication was observed in any patients. Conclusion: VC-ERV  provides
      significantly  lower  Ppeak  and  higher  Cdyn  with  similar  oxygenation, 
      ventilation,  hemodynamic  parameters, and Pmean levels when compared to VC-CRV
      during mechanical ventilation with RM and PEEP in laparoscopic sleeve
      gastrectomy.

PMID- 30119153
TI  - Efficacy and safety of lenalidomide and dexamethasone in patients with
      relapsed/refractory multiple myeloma: a real-life experience
AB  - Background/aim: In  Turkey,  lenalidomide  plus  dexamethasone  (RD)  has  been 
      used  to  treat  relapsed/refractory  multiple  myeloma  (RRMM)  since  2010. 
      This  retrospective,  single-center  study  evaluated  the  efficacy  and 
      tolerability  of  RD  in  patients  with  RRMM  between October 2010 and June
      2016. Materials and methods: Patients' records were reviewed, and overall (OS)
      and progression-free survival (PFS) were assessed. Results: One hundred and
      twenty patients (71 males; 59.2%) were included in the study. The median number
      of prior lines of treatment was one (1-4); 72 patients (60.0%) received RD as
      second-line therapy and 51 patients (42.5%) had previously undergone autologous
      stem cell transplantation (ASCT). The overall response rate was 72.5%, with 19%
      of these patients achieving a complete response. The median length of follow-up
      and duration of response to RD was 14 months and 19 months, respectively. Median
      OS and PFS were 32 and  21  months,  respectively.  Prior  ASCT,  an  overall 
      response,  and  treatment  with  RD  for  >12  cycles  were  identified  as 
      independent  prognostic factors for OS and PFS. Adverse events (AEs) occurred in
      69 (57.5%) and 14 patients (11.7%) discontinued treatment due to AEs. Conclusion:
      We found RD to be safe, well tolerated, and effective in RRMM in everyday
      clinical practice in Turkey.

PMID- 30119154
TI  - What has changed in the utility of pediatric EEG over the last decade?
AB  - Background/aim: We evaluated the utility of electroencephalography (EEG) in
      children with neurological conditions and compared the results with those of our
      previous study on excessive uses of pediatric EEG, which was published in 2003.
      We also evaluated the possibility  of  subsequent  EEGs  and  satisfactory 
      duration  of  EEG  recordings  according  to  EEG  type  and  admission  status. 
      We  also  evaluated the yield of varying durations of EEG recordings. Materials
      and methods: All consecutive pediatric EEG records performed at Gazi University
      EEG laboratory during a 1-year period were retrospectively reviewed. The
      indications of EEGs, the number of EEGs for each patient, condition and duration
      of EEG records, and activation techniques were evaluated in terms of detection of
      abnormalities by EEG. Results: We reviewed a total of 2045 EEGs in children aged
      2 months-20 years. Of these, 776 were repeat EEGs (38%) and 485 recordings were 
      >=30  min  (23.7%);  98%  of  EEG  abnormalities  appeared  in  the  first  30 
      min.  Overall,  90.5%  of  EEGs  were  ordered  by  a  pediatric  neurologist.
      There were similar requests for numbers of EEGs, but the rate of abnormal EEGs
      (43.6%) was significantly higher when compared to that of our previous study
      (36.2%). Conclusion: The results of this study show that the utility of EEG
      becomes more selective and interpretation of pediatric EEG improves depending on
      the increasing number of pediatric neurologists. A duration of 20-30 min of EEG
      recording is sufficient, on the condition of inclusion of nREM sleep records.

PMID- 30119155
TI  - The impact of donor and recipient KIR genes and KIR ligands on the occurrence of
      acute graft-versus-host disease and graft survival after HLA-identical sibling
      hematopoietic stem cell transplantation
AB  - Background/aim: After  allogeneic  hematopoietic  stem  cell  transplantation 
      (allo-HSCT),  donor  natural  killer  (NK)  cells  trigger  alloreactions 
      against  potential  recipient  cells  by  their  killer  immunoglobulin-like 
      receptors  (KIRs).  This  study  investigated  whether  KIR/HLA genotypes and KIR
      haplotypes of donors and recipients exhibit a critical function in the prevalence
      of acute graft-versus-host disease (aGVHD) and persistence of the graft after HLA
      identical sibling allo-HSCT for patients with hematological malignancies.
      Materials and methods: We  studied  KIR  and  HLA  genotypes  in  115  related 
      donors  and  recipients  (56  patients  with  AML  and  59  patients  with  ALL) 
      who  had  received  allo-HSCT  from  HLA-matched  sibling  donors.  We  evaluated
      17  KIR  genes  and  some  alleles,  including their ligands, using the PCR-SSP
      assay. Results: KIR gene frequency results between donors and recipients showed
      that donors had more activating KIR than their recipients. Chi-square comparison
      of KIR genotype frequencies in donors versus recipients revealed a significant
      difference (P < 0.001). We found a survival association between the donor lacking
      and the recipient having group B KIR haplotypes, although this was not
      statistically significant. Conclusion: This study suggests that we could exploit
      NK cell alloreactivity as a part of the optimization of donor selection and
      potential immunotherapeutic regimens to help facilitate good engraftment and
      reduce the risk of aGVHD incidence after allo-HSCT.

PMID- 30119156
TI  - Reliability and validity of the Turkish version of Pain Assessment Checklist for
      Seniors with Limited Ability to Communicate (PACSLAC-T)
AB  - Background/aim: This study aimed to assess validity and reliability of the
      Turkish version of Pain Assessment Checklist for Seniors with Limited Ability to
      Communicate (PACSLAC-T). Materials and methods: The  individuals  who  met 
      inclusion  criteria  of  the  study  were  in  patients  of  a  hospital  and  a 
      long-term  care  facility.  Mini  Mental  Status  Exam  (MMSE),  Cornell 
      Dementia  Depression  Scale  (CDDS),  Global  Deterioration  Scale  (GDS), 
      visual  analogue scale (VAS), and PACSLAC-T were administered to all subjects.
      The scales were repeated with an interval of two weeks for test-retest
      reliability. Results: A  total  of  112  patients  with  dementia  were  included
      in  the  study.  The  intraclass  correlation  coefficient  ICC  for  test
      retest  reliability of the PACSLAC-T was 0.713 with a 95% confidence interval of
      0.486-0.843. The Cronbach's alpha coefficient for total PACSLAC-T was 0.842 for
      test and 0.888 for retest, which indicated substantial internal consistency. In
      convergent validity, there were significant correlations between PACSLAC-T total
      score VAS (r = 0.684, P < 0.001), while no correlation was found between PACSLAC
      T total score and CDDS (r = 0.127, P = 0.094), and GDS (r = 0.096, P = 0.167).
      Also, significant correlations were found between PACSLAC-T total score and MMSE
      (r = -0.468, P = 0.016). Conclusion: This study showed that PACSLAC-T could be a
      promising tool for the management of pain in older adults with limited
      communication skills.

PMID- 30119157
TI  - The validity and reliability of the Turkish version of the Leicester Cough
      Questionnaire in COPD patients
AB  - Background/aim: The reliability and validity of the Turkish version of the
      Leicester Cough Questionnaire (LCQ) have been evaluated before. This study aimed
      to validate the Turkish version of the LCQ in chronic obstructive pulmonary
      disease (COPD) patients with cough. Materials and methods: COPD (GOLD B, C, D)
      patients over age 40 (n = 75) and healthy volunteers as a control group (n = 75)
      were included.  A  sociodemographic  data  form,  the  LCQ,  the  Short  Form-36 
      (SF-36)  quality  of  life  questionnaire,  and  the  World  Health  Organization
      Quality of Life Brief Form for Turkish people were completed. The internal
      reliability of the LCQ was determined using the Cronbach alpha coefficient (>0.6)
      and its repeatability by the intraclass consistency coefficient (P < 0.05) was
      accepted as significant. Results: For internal consistency, Cronbach alpha
      coefficients of all subscales of the LCQ, physical, psychological, and social,
      were found as 0.72, 0.86, and 0.83, respectively, with 0.92 for the total index.
      There was significant internal consistency for all subscales and the total index
      (Cronbach alpha coefficients of >0.6). In test-retest reliability, the
      correlation coefficient ranged between 0.71 and 0.80 for each question and was
      calculated as r = 0.89 for total LCQ score (P < 0.001). Conclusion: The Turkish
      version of the LCQ has been found to have acceptable reliability and validity for
      use in Turkish COPD patients with chronic cough.

PMID- 30119158
TI  - Detection of the differences in the apparent diffusion coefficient values in
      different histopathological types of malignant breast lesions and comparison of
      cellular region/stroma ratio and histopathological results
AB  - Background/aim: This study aimed to compare the apparent diffusion coefficient
      (ADC) values of malignant breast lesions with different histopathological types
      on diffusion-weighted imaging (DWI) and the cellular region/stroma (CR/S) ratio
      and histopathological results. Materials and methods: Breast  diffusion-weighted 
      magnetic  resonance  findings  of  59  patients  were  retrospectively  analyzed 
      for  malignant breast lesions. The CR/S ratio was calculated using breast wide
      excisional biopsy or mastectomy specimens. Results: Receiver operating
      characteristic analysis was performed for malignant lesions and subtypes. An ADC
      threshold of 1.260 * 10-3 mm2/s was set to detect invasive ductal carcinoma with
      80.8% sensitivity and 81.4% specificity. An ADC threshold of 1.391 * 10-3mm2/s
      was set to detect invasive lobular carcinoma lesions with 88.2% sensitivity and
      79.5% specificity. The ADC value for lesions with low CR/S ratio (n = 21) was
      1.135 +/- 0.429 * 10-3 mm2/s and it was 1.155 +/- 0.429 * 10-3 mm2/s in the high
      CR/S ratio group (n = 18). Conclusion: ADC value calculation does not seem to be
      used as an alternative for histopathological detection, which is the gold
      standard for the differentiation of subtypes of malignant breast cancer. In
      addition, since there is a positive correlation between CR/S ratio and ADC
      values, it may be a strong marker to evaluate the stromal component of lesions.

PMID- 30119159
TI  - Rising stars of DPLD survival: FVC and exercise desaturation (a single-center
      study)
AB  - Background/aim: Diffuse  parenchymal  lung  diseases  (DPLDs)  comprise  a 
      broad,  heterogeneous  group  of  diseases  with  common  functional 
      characteristics  and  a  common  final  pathway,  usually  leading  to 
      irreversible  fibrosis.  We  investigated  the  effects  of  the  physiological
      and functional parameters and of pulmonary hypertension (PH) on survival in
      DPLDs. Materials and methods: The study included 158 patients with DPLDs. Patient
      data were examined retrospectively, and survival status was obtained through
      phone calls. Results: Patients were divided into five groups according to their
      diagnosis: idiopathic pulmonary fibrosis (IPF), non-IPF idiopathic interstitial 
      pneumonias,  connective  tissue  diseases,  sarcoidosis,  and  other  DPLDs. 
      Median  survival  was  42.9  months.  The  significant  negative  effects  of 
      older  age,  presence  of  delta  saturation  (DeltaSat;  difference  between 
      oxygen  saturation  at  rest  and  after  the  6-min  walking  test),  6-min 
      walking  distance  (<350  m),  systolic  pulmonary  artery  pressure  (sPAP; 
      >=50  mmHg),  and  baseline  percentage  of  diffusing capacity of the lungs for
      carbon monoxide (<80%) with percentage of forced vital capacity (FVC%; <80%) were
      detected on survival (P < 0.05). A one-unit decrease in FVC% was related to a 6%
      increase in mortality. Another unique finding indicated that higher DeltaSat
      (>10%) correlated strongly with sPAP (>50 mmHg) and thus with a worse survival
      rate. Conclusion: The current study determined that FVC% is important in the
      prediction of mortality. Moreover, it demonstrated a strong relationship between
      exercise desaturation and PH.

PMID- 30119160
TI  - Effect of intravitreal bevacizumab on macular thickness: exploring serum and
      vitreous proangiogenic biomarkers in patients with diabetic macular edema
AB  - Background/aim: This  study  evaluates  diabetic  macular-edema  (DME)  patients 
      for  the  effect  of  intravitreal  bevacizumab  (IVB)  injection on macular
      thickness and proangiogenic biomarkers in serum and vitreous. Materials and
      methods: Forty DME patients were analyzed for macular thickness (MT). Twelve
      proangiogenic biomarkers in serum and vitreous were analyzed before and after
      IVB. Results: Significant decrease in MT with vitreal vascular endothelial growth
      factor-A (VEGF-A) was observed as expected after IVB, while serum VEGF-A did not
      follow a decreasing trend in contrast to VEGF-C, which decreased both in serum
      and vitreous. Other vitreal factors like bone morphogenetic protein-9 (BMP9) and
      fibroblast growth factor (FGF) were also significantly decreased, while
      endothelial growth factor (EGF) increased following IVB. Before IVB, significant
      negative correlations were vitreous BMP9 with serum FGF, vitreous human growth
      factor (HGF) and interleukin-8 (IL-8) with serum endothelin, and vitreous and
      serum FGF and serum placental growth factor (PLGF) with EGF. After IVB, negative
      correlations in serum vs. vitreous were found for both HGF and PLGF with BMP9,
      and angiopoietin with FGF. Cube average thickness was negatively correlated with
      serum FGF and positively correlated with vitreous PLGF and endothelin.
      Conclusion: Vascular endothelial growth factors are not the only factors that
      cause macular edema in diabetic patients. The effect of IVB on different
      proangiogenic biomarkers indicated a complex interplay of other factors in DME.

PMID- 30119161
TI  - Hand functions in systemic lupus erythematosus: a comparative study with
      rheumatoid arthritis patients and healthy subjects
AB  - Background/aim: Systemic  lupus  erythematosus  (SLE)  frequently  affects  the 
      small  joints  of  the  hand  and  may  result  in  difficulty  in  activities of
      daily living. There are very few studies evaluating the problems encountered in
      the hands in patients with SLE. The aim of this study is to evaluate hand
      functions in patients with SLE and compare them with rheumatoid arthritis (RA)
      patients and healthy subjects. Materials and methods: A total 46 female patients
      meeting the SLE classification criteria were recruited. Similarly, 51 female RA
      patients and 46 healthy female subjects served as the control groups. To assess
      the upper extremity disability level, the Disability Arm Shoulder and Hand
      Questionnaire (DASH) was used. Some functional performances such as hand grip and
      pinch strength were evaluated using a dynamometer and the Nine Hole Peg Test
      (NHPT), respectively. Results: Hand  functions  were  found  to  be  impaired  in
      both  SLE  and  RA  patients  when  compared  to  healthy  controls.  In 
      addition,  patients with SLE showed better performance in the NHPT, hand grip,
      and pinch strength than RA patients (P < 0.05). However, the patient-reported
      disability level was similar in both patient groups (P > 0.05). Conclusion:
      Similar to patients with RA, hand functions are significantly impaired in
      patients with SLE in daily activities.

PMID- 30119162
TI  - Peripheral arterial disease increases the risk of multidrug-resistant bacteria
      and amputation in diabetic foot infections
AB  - Background/aim: The  aim  of  this  study  was  to  investigate  the 
      microbiological  profile  and  resistance  rates  of  diabetic  foot  infections 
      (DFIs) and to determine the effect of peripheral arterial disease (PAD) on the
      microbiology, clinical condition, and treatment outcomes. Materials and methods:
      Characteristics, laboratory and imaging data, and the treatment modalities of
      patients admitted to our hospital with a diagnosis of DFI (PEDIS classification 3
      4) during 2005-2016 were analyzed according to the presence of PAD. Results: Of
      112 patients who were included in this study, 86 (76.8%) had PAD. Patients with
      PAD were older and had higher amputation rates (P < 0.05). A microbiological
      profile of patients revealed a predominance of gram-positive bacteria (57.1%).
      Staphylococcus aureusand Streptococcus spp.were the most frequently encountered
      bacteria. Incidence of Pseudomonas spp. infection was higher in the PAD group  (P
      <  0.05).  Of  all  patients,  24.1%  had  multidrug-resistant  (MDR) 
      microorganisms  in  their  wound  cultures.  Presence  of  MDR  bacteria in
      patients with PAD was 4.9-fold higher than that in patients without PAD (P <
      0.05). Conclusion: This retrospective study indicates that PAD has a significant
      role, especially in elderly patients with DFIs. Patients should be promptly
      evaluated and treated for PAD to prevent infections with resistant microorganisms
      and limb loss.

PMID- 30119163
TI  - Ketamine dosing for sedation during repeated radiotherapy sessions in children
AB  - Background/aim: We report the analysis of ketamine doses needed and the recovery
      times in pediatric oncology patients undergoing repeated radiotherapy sessions.
      Materials and methods: In  a  single-blind  prospective  study  design,  thirty
      three  pediatric  patients  undergoing  radiotherapy  due  to  oncologic 
      disorders  received  2  mg/kg  ketamine  and  10  MUg/kg  atropine  intravenously
      and  the  rescue  drug  to  be  administered  was  ketamine at 0.5 mg/kg when
      the sedation level was inadequate. Total ketamine consumption, additional doses,
      and recovery time were recorded. Results: Data of 635 consecutive radiotherapy
      sessions were evaluated. There was no significant alteration in total ketamine
      consumption required to complete the radiotherapy periods during consecutive
      procedures (P > 0.05). However, the recovery times started to decrease by the
      fourth session (P = 0.02) and continued to decrease onwards during the whole
      study period (P = 0.001). The mean of the first recovery time was 13.68 +/- 3.99
      min, whereas the mean of the last recovery time was 7.66 +/- 6.35 min.
      Conclusion: A requirement for an incremental increase in ketamine dose after
      subsequent administrations was not detected, despite a  significant  decrease  in
      recovery  times  being  anticipated  when  ketamine  is  used  repeatedly  for 
      sedative  purposes  in  consecutive  radiotherapy sessions.

PMID- 30119165
TI  - Neuroprotective effects of pinocembrin on ischemia/reperfusion-induced brain
      injury by inhibiting autophagy.
AB  - BACKGROUND: Cerebral ischemia/reperfusion (I/R) injury is a common pathological
      process after cardiac arrest, shock and acute cerebral infarction recanalization,
      which causes serious injury in brain function. Pinocembrin (Pino), a natural
      flavonoid at the highest concentration in propolis, exhibited a variety of
      biological effects, including antitumor, antimicrobial and anti-inflammatory
      activities. However, the effects of Pino on brain injured after I/R and the
      mechanisms of its neuroprotective effects remain elusive. METHODS: In the present
      study, we used I/R model rats underwent transient cerebral ischemia inducing by
      four-vessel occlusion and reperfusion. Pino alone or in combination with
      autophagy inducer rapamycin (RAPA) was administered to I/R rats. The behavior and
      cognitive function were evaluated by open field test and Morris water maze test.
      HE staining was used to determine the survival of hippocampus CA1 pyramidal
      cells. Three key proteins of autophagy, LC3, Beclin1 and p62, were detected by
      Western blot. RESULTS: Our results showed that Pino could significantly reduce
      the damage of hippocampus CA1 pyramidal neurons and alleviate the impairments of
      behavior and cognitive function in I/R rats. Pino also decreased the expression
      of LC3II and Beclin1 and increased the level of p62 in hippocampus CA1 of I/R
      rats. In addition, Pino also decreased RAPA-induced neuronal damage and excessive
      activation of autophagy in I/R rats. CONCLUSIONS: Taken together, these results
      suggested that Pino could protect the brain injury induced by I/R and the
      potential mechanisms might attribute to inhibition of autophagy activity.

PMID- 30119164
TI  - Methodology of a new inflammatory arthritis registry: TReasure
AB  - Background/aim: The TReasure registry, created in 2017, is an observational
      multicenter cohort that includes inflammatory arthritis patients.  This  article 
      reviews  the  methodology  and  objectives  of  the  TReasure  registry 
      established  to  collect  data  from  rheumatoid  arthritis (RA) and
      spondyloarthritis (SpA) patients. Methodology: Fifteen  rheumatology  centers  in
      Turkey  will  contribute  data  to  the  TReasure  database.  The  actual 
      proprietor  of  the  database  is  the  Hacettepe  Rheumatology  Association 
      (HRD)  and  Hacettepe  Financial  Enterprises.  Pharmaceutical  companies  that 
      operate in Turkey (in alphabetical or er), Abbvie, Amgen, BMS, Celltrion
      Healthcare, Novartis, Pfizer, Roche, and UCB, support the TReasure registry.
      TReasure is a web-based database to which users connect through a URL
      (https://www.trials-network.org/treasure) with  their  unique  identifier  and 
      passwords  provided  for  data  entry  and  access.  TReasure  records 
      demographic  and  clinical  features,  comorbidities, radiology and laboratory
      results, measures of disease activity, and treatment data. Discussion: TReasure
      will provide us with various types of data, such as a cross-sectional view of the
      current nationwide status of the patients currently receiving these treatments,
      and retrospective data as much as allowed by the participating centers' records.
      Finally, a high-quality prospective dataset will be built over the ensuing years
      from patients with a new diagnosis of RA or SpA.

PMID- 30119166
TI  - Novel drug delivery systems for NSAIDs in management of rheumatoid arthritis: An
      overview.
AB  - Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by
      chronic joint inflammation which ultimately leads to severe disability and
      premature mortality. It has a global prevalence of around 1% with the incidence
      among women being 2-3 times more than in men. The pathogenesis of the disease
      involves preclinical RA, genetic factors, and environmental factors. The RA has
      no known cure and the primary aim of treatment remains to attain lowest possible
      disease activity and recovery if possible. The present review highlights the
      literature on the different treatment options available for the treatment of RA,
      their mechanisms of action, side effects, and novel drug delivery systems that
      are in use for drug administration with the main focus on novel drug delivery
      systems of non-steroidal anti-inflammatory drugs. Different classes of drugs such
      as corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs) and disease
      modifying anti-rheumatic drugs (DMARDs), and biologics are discussed with
      examples of most widely used drugs among each class. Conventional drug therapy
      has many disadvantages like low solubility and permeability, poor
      bioavailability, degradation by gastrointestinal enzymes, first pass metabolism,
      food interactions, and toxicity. Novel drug delivery systems like microspheres,
      nanoparticles, dendrimers, liposomes, and so on are promising tools as they have
      been successful in overcoming the disadvantages associated with conventional drug
      delivery system. The present review squares the various novel drug delivery
      systems that have been explored for administering anti-rheumatic drugs and the
      advantages associated with these novel drug delivery systems in comparison to
      conventional drug delivery systems.

PMID- 30119167
TI  - Rho kinase, a potential target in the treatment of metabolic syndrome.
AB  - INTRODUCTION: Metabolic syndrome is a health issue which is recognized due to its
      insulin resistance, central obesity, dyslipidemia, and hypertension. Since the
      Rho family of GTPases are involved in several cellular mechanisms, it is believed
      they might be involved in different aspects of metabolic syndrome. We conducted a
      search of some databases such as PubMed for articles and reviews published
      between 1997 and 2017, with different keywords including "metabolic syndrome",
      "rho kinase", "dyslipidemia", "hypertension", "central obesity", "insulin
      resistance" and the connectors AND or OR. Studies revealed that Rho kinase over
      activity leads to cardiovascular diseases, such as hypertension and dyslipidemia,
      through decreasing NO production. Since NO has beneficial effects on lipid
      metabolism through activation of hepatic sterol regulatory element-binding
      protein (SREBP)-2, its inhibition can contribute to higher levels of LDL
      cholesterol and also results in increased myosin light chain activation with
      vasoconstriction. Moreover, Rho kinase enhances insulin substrate 1 (IRS-1)
      phosphorylation, leading to the development of insulin resistance. CONCLUSION: In
      conclusion, the present review demonstrates that upregulated Rho kinase activity
      involves in the pathogenesis of all aspects of metabolic syndrome. Taken
      together, these results implicate the therapeutic potential of the Rho-kinase
      pathway as an important new target in medicine.

PMID- 30119169
TI  - Novel approaches in the treatment of diabetic cardiomyopathy.

PMID- 30119168
TI  - Aquilariae Lignum extract attenuates glutamate-induced neuroexcitotoxicity in
      HT22 hippocampal cells.
AB  - An imbalance between excitatory and inhibitory neurotransmitters is known to
      induce neuronal excitotoxicity which is a major cause of neurodegenerative
      disorders. Excessive glutamate concentration leads to the neuronal death by
      increasing oxidative stress and affecting the apoptotic signaling pathway. We
      investigated the anti-excitotoxic effects and associated working mechanisms of
      30% ethanol extract of Aquilariae Lignum (ALE) against hippocampal neuronal death
      by glutamate. HT22 cells were treated with glutamate (20 mM) for 24 h following
      pretreatment with ALE (5, 10, 25 MUg/mL). Cell viability, biochemical analysis,
      flow chemistry, and Western blotting assays were performed. Glutamate treatment
      substantially increased the intracellular level of reactive oxygen species (ROS)
      and Ca2+ influx into the cell, which were followed by apoptosis. ALE
      pretreatment, however, significantly attenuated these excitotoxicity-related
      features according to the results of Annexin V analysis and the lactate
      dehydrogenase assay, in which the calpain pathway (in a caspase 3-independent
      manner) may be involved. ALE pretreatment also significantly attenuated the
      glutamate-induced activation of both inflammation-associated molecules
      (extracellular signal-regulated kinase, c-Jun N-terminal kinases and p38) and
      death-related molecules (p53, apoptosis-inducing factor). The inactivation of
      brain-derived neurotrophic factor (BDNF) was restored by ALE pretreatment. Our
      results verified that A. Lignum has potential neuroprotective effects on
      glutamate-induced excitotoxicity in hippocampal neuron cells, and its underlying
      mechanism may involve the regulation of ROS-mediated cell death pathways.

PMID- 30119170
TI  - MiR-32 promotes tumorigenesis of colorectal cancer by targeting BMP5.
AB  - MiRNA regulation is a crucial way of epigenetic changes. Mir-32 has been reported
      in several studies as an oncogene, however, its role and target in colorectal
      cancer (CRC) remains unclear. In this study, we aimed to explore the role of miR
      32 in CRC using bioinformatic analysis and functional assays. We collected 28
      pairs of CRC tumor tissues and adjacent normal tissues and confirmed miR-32 was
      significantly upregulated in CRC. Expression and clinical data from The Cancer
      Genome Atlas (TCGA) identified miR-32 expression is associated with CRC lymphatic
      invasion, metastasis, and correlates with patients' poor survival. Functional
      studies demonstrated that overexpression of miR-32 in LoVo cells promoted cell
      proliferation and migration, whereas inhibition of miR-32 in HCT 116 cells showed
      the opposite results. Using bioinformatics, we identified Bone morphogenetic
      protein 5 (BMP5) is a direct target of miR-32, and loss of tumor suppressor BMP5
      may partially due to the miR-32 dysregulation. The inverse correlation between
      miR-32 and BMP5 was observed in CRC, especially in advanced tumor patients.
      Moreover, cotransfection of miR-32 mimics and BMP5 recombinant vector in LoVo
      cells demonstrated that BMP5 could reverse the oncomir effect of miR-32. Taken
      together, our results suggested a significant role of miR-32/BMP5 axis in CRC
      tumorigenesis.

PMID- 30119171
TI  - Cellular phenotypes as inflammatory mediators in Parkinson's disease:
      Interventional targets and role of natural products.
AB  - Pathogenesis of Parkinson's disease (PD) is undoubtedly a multifactorial
      phenomenon, with diverse etiological agents. Pro-inflammatory mediators act as a
      skew that directs disease progression during neurodegenerative diseases.
      Understanding the dynamics of inflammation and inflammatory mediators in
      preventing or reducing disease progression has recently gained much attention.
      Inflammatory neuro-degeneration is regulated via cytokines, chemokines, lipid
      mediators and immune cell subsets; however, individual cellular phenotypes in the
      Central Nervous System (CNS) acts in diverse ways whose persistent activation
      leads to unresolving inflammation often causing unfavorable outcomes in
      neurodegenerative disease like PD. Specifically, activation of cellular
      phenotypes like astrocytes, microglia, activation of peripheral immune cells
      requires different activation signals and agents like (cytokines, misfolded
      protein aggregates, infectious agents, pesticides like organophosphates, etc.,).
      However, what is unknown is how the different cellular phenotypes respond
      uniquely and the role of the factors they secrete alters the signal cascades in
      the complex neuron-microglial connections in the CNS. Hence, understanding the
      role of cellular phenotypes and the inflammatory mediators, the cross talk among
      the signals and their receptors can help us to identify the potential therapeutic
      target using natural products. In this review we have tried to put together the
      role of cellular phenotypes as a skew that favors PD progression and we have also
      discussed how the lack of experimental approaches and challenges that affects
      understanding the cellular targets that can be used against natural derivatives
      in alleviating PD pathophysiology. Together, this review will provide the better
      insights into the role of cellular phenotypes of neuroinflammation, inflammatory
      mediators and the orchestrating factors of inflammation and how they can be
      targeted in a more specific way that can be used in the clinical management of
      PD.

PMID- 30119172
TI  - Involvement of JNK1/2-NF-kappaBp65 in the regulation of HMGB2 in myocardial
      ischemia/reperfusion-induced apoptosis in human AC16 cardiomyocytes.
AB  - JNK1/2 and NF-kappaB signal are essential signaling pathways that mediate a
      variety of cellular processes, including cell survival, apoptosis, inflammation
      and angiogenesis. JNK1/2 activation and NF-kappaBp65 nuclear translocation have
      been found in ischemia/reperfusion (I/R)-induced injury. However, the regulation
      of JNK1/2-NF-kappaBp65 signaling pathway remains unclear. To examine the function
      and possible mechanism of HMGB2 in I/R-induced cell injury, human AC16
      cardiomyocytes transfected with pLVX-Puro-HMGB2 were treated with SP600125
      (JNK1/2 inhibitor) or PDTC (NF-kappaB inhibitor) and that following I/R injury
      were transfected with HMGB2-shRNA. The cell proliferation and apoptosis were
      measured by CCK-8, flow cytometry and TUNEL, respectively. The expression of
      HMGB2, Cleaved PARP and Caspase-3, Bax and Bcl-2 and activity of MAPKs and NF
      kappaBp65 were measured by Western blot. Here, we found that I/R time-dependently
      induced the increase in the expression of HMGB2 in AC16 cardiomyocytes. HMGB2
      silencing significantly inhibited I/R-induced the cell proliferation reduction,
      cell apoptosis, activation of ERK1/2, JNK1/2 and NF-kappaBp65, increased Bax,
      Cleaved PARP and Caspase-3 and decreased Bcl-2 expression. HMBG2 overexpression
      mimicked the effect of I/R-induced injury in AC16 cardiomyocytes, which was
      reversed by treatment with SP600125 or PDTC. Moreover, PDTC treatment in rats
      following I/R injury also showed decreases in the cell apoptosis, HMGB2, Cleaved
      PARP and Caspase-3 and Bax expression, and JNK1/2 activation. Taken together, our
      findings suggest that HMBG2 overexpression promotes I/R-induced cell apoptosis
      through activating the JNK1/2-NF-kappaBp65 signaling in AC16 cardiomyocytes.

PMID- 30119173
TI  - miR-539 enhances chemosensitivity to cisplatin in non-small cell lung cancer by
      targeting DCLK1.
AB  - microRNAs (miRNAs) have been implicated to play critical roles in non-small
      celllung cancer (NSCLC) progression and participate in the regulation of drug
      resistance during cancer chemotherapy. However, the underlying molecular
      mechanism of how miR-539 modulates the chemosensitivity to cisplatin (DDP) in
      NSCLC cells remains largely unknown. In this study, we found that miR-539 was
      significantly downregulated in DDP-resistant cell lines (A549/DDP and H1299/DDP).
      Overexpression of miR-539 enhanced the sensitivity of DDP-resistant NSCLC cells
      to DDP by suppressing cell proliferation, causing cell cycle arrest, inducing
      apoptosis, repressing invasion and migration. Whereas, downregulation of miR-539
      inhibited the sensitivity of parental NSCLC cells to DDP by promoting cell
      proliferation and decreasing DDP-induced apoptosis. Furthermore, the luciferase
      report assay identified doublecortin-like kinase 1 (DCLK1) was a direct target of
      miR-539. Knockdown of DCLK1 mimicked the function of miR-539-mediated cell
      chemosensitivity in DDP-resistant NSCLC cells, while restoration of DCLK1
      reversed the effect of miR-539 overexpression. We also found that P13 K/AKT/mTOR
      signaling pathway was also involved in miR-539/DCLK1 axis -mediated
      chemosensitivity in DDP-resistant NSCLC cells. Additionally, the downregulation
      of miR-539 was closely correlated with severe clinicopathological parameters
      including the upregulation of DCLK1, chemosensitivity to DDP, and tumor
      aggressiveness in NSCLC patients. In conclusion, miR-539 increased the
      chemosensitivity to DDP in NSCLC cells by directly targeting DCLK1, which might
      provide potential biomarkers for DDP-resistant NSCLC therapy.

PMID- 30119174
TI  - Novel steroid derivatives: synthesis, antileishmanial activity, mechanism of
      action, and in silico physicochemical and pharmacokinetics studies.
AB  - The search for new drugs for the treatment of leishmaniasis is an important
      strategy for improving the current therapeutic arsenal for the disease. There are
      several limitations to the available drugs including high toxicity, low efficacy,
      prolonged parenteral administration, and high costs. Steroids are a diverse group
      of compounds with various applications in pharmacology. However, the
      antileishmanial activity of this class of molecules has not yet been explored.
      Therefore, in the present study, we investigated the antileishmanial activity and
      cytotoxicity of novel steroids against murine macrophages with a focus on the
      derivatives of cholesterol (CD), cholic acid (CA), and deoxycholic acid (DA).
      Furthermore, the mechanism of action of the best compound was assessed, and in
      silico studies to evaluate the physicochemical and pharmacokinetic properties
      were also conducted. Among the sixteen derivatives, schiffbase2, CD2 and
      deoxycholic acid derivatives (DOCADs) were effective against promastigotes of
      Leishmania species. Despite their low toxicity to macrophages, the majority of
      DOCADs were active against intracellular amastigotes of L. amazonensis, and
      DOCAD5 exhibited the best biological effect against these parasitic stages (IC50
      = 15.34 MUM). Neither the CA derivatives (CAD) nor DA alone inhibited the
      intracellular parasites. Thus, the absence of hydroxyl in the C-7 position of the
      steroid nucleus, as well as the modification of the acid group in DOCADs were
      considered important for antileishmanial activity. The treatment of L.
      amazonensis promastigote forms with DOCAD5 induced biochemical changes such as
      depolarization of the mitochondrial membrane potential, increased ROS production
      and cell cycle arrest. No alterations in parasite plasma membrane integrity were
      observed. In silico physicochemical and pharmacokinetic studies suggest that
      DOCAD5 could be a good candidate for an oral drug. The data demonstrate the
      potential antileishmanial effect of certain steroid derivatives and encourage new
      in vivo studies.

PMID- 30119175
TI  - Ginsenoside Re inhibits vascular neointimal hyperplasia in balloon-injured
      carotid arteries through activating the eNOS/NO/cGMP pathway in rats.
AB  - Ginsenoside Re (GS-Re) is one of the main ingredients of ginseng, a widely known
      Chinese traditional medicine, and has a variety of beneficial effects, including
      vasorelaxation, antioxidative, anti-inflammatory, and anticancer properties. The
      aims of the present study were to observe the effect of GS-Re on balloon injury
      induced neointimal hyperplasia in the arteries and to investigate the mechanisms
      underlying this effect. A rat vascular neointimal hyperplasia model was generated
      by rubbing the endothelium of the common carotid artery (CCA) with a balloon, and
      GS-Re (12.5, 25 or 50 mg/kg/d) were subsequently continuously administered to the
      rats by gavage for 14 days. After GS-Re treatment, the vessel lumen of injured
      vessels showed significant increases in the GS-Re 25.0 and 50.0 mg/kg/d
      (intermediate- and high-dose) groups according to H.E. staining. Additionally, a
      reduced percentage of proliferating cell nuclear antigen (PCNA)-positive cells
      and an increased number of SM alpha-actin-positive cells were detected, and the
      levels of NO, cyclic guanosine monophosphate (cGMP), and eNOS mRNA as well as the
      phos-eNOSser1177/eNOS protein ratio were obviously upregulated in the
      intermediate- and high-dose groups. Moreover, the promotive effects of GS-Re on
      NO and eNOS expression were blocked by L-NAME treatment to different degrees.
      These results suggested that GS-Re can suppress balloon injury-induced vascular
      neointimal hyperplasia by inhibiting VSMC proliferation, which is closely related
      to the activation of the eNOS/NO/cGMP pathway.

PMID- 30119176
TI  - Photodynamic therapy - mechanisms, photosensitizers and combinations.
AB  - Photodynamic therapy (PDT) is a modern and non-invasive form of therapy, used in
      the treatment of non-oncological diseases as well as cancers of various types and
      locations. It is based on the local or systemic application of a photosensitive
      compound - the photosensitizer, which is accumulated in pathological tissues. The
      photosensitizer molecules absorb the light of the appropriate wavelength,
      initiating the activation processes leading to the selective destruction of the
      inappropriate cells. The photocytotoxic reactions occur only within the
      pathological tissues, in the area of photosensitizer distribution, enabling
      selective destruction. Over the last decade, a significant acceleration in the
      development of nanotechnology has been observed. The combination of
      photosensitizers with nanomaterials can improve the photodynamic therapy
      efficiency and eliminate its side effects as well. The use of nanoparticles
      enables achievement a targeted method which is focused on specific receptors,
      and, as a result, increases the selectivity of the photodynamic therapy. The
      object of this review is the anticancer application of PDT, its advantages and
      possible modifications to potentiate its effects.

PMID- 30119177
TI  - Analyses of long non-coding RNA and mRNA profiles in right ventricle myocardium
      of acute right heart failure in pulmonary arterial hypertension rats.
AB  - We investigated the changes in expression profile and potential roles of long
      noncoding RNAs (lncRNAs) in right ventricle (RV) myocardium of pulmonary arterial
      hypertension (PAH) rats with RV failure induced by acute inflammation. Sprague
      Dawley rats were given monocrotaline to establish a PAH model and acute heart
      failure was induced by an injection of lipopolysaccharide. The RV failure was
      confirmed by echocardiography data. The expression profiles of lncRNAs and
      messenger RNAs (mRNAs) in RV tissues were obtained by RNA sequencing.
      Bioinformatics analyses were performed, including Gene Ontology (GO) analysis,
      Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and co-expression network
      analysis. We also conducted real-time quantitative polymerase chain reaction (qRT
      PCR) to confirm the results of RNA sequencing. A total of 169 lncRNAs (101
      upregulated and 68 down-regulated) and 898 mRNAs (623 upregulated and 275 down
      regulated) were differently expressed in PAH rats with acute RV failure. The
      expression levels of lncRNA (TCONS_00052110, TCONS_00201718, TCONS_00094247, and
      TCONS_00296056) and mRNA (Cxcl-1 and Timp4) were verified through qRT-PCR, the
      results of which were consistent with RNA sequencing. lncRNA expression data in
      RV myocardium of PAH rats with acute RV failure will provide important insights
      about the contribution of lncRNAs to heart failure in PAH model.

PMID- 30119178
TI  - Boerhaavia diffusa inhibits key enzymes linked to type 2 diabetes in vitro and in
      silico; and modulates abdominal glucose absorption and muscle glucose uptake ex
      vivo.
AB  - The present study investigated the in vitro and ex vivo antioxidant, anti
      diabetic and anti-obesogenic potentials of different solvent (ethyl acetate,
      ethanol and water) extracts from the aerial parts of Boerhaavia diffusa. The
      ferric reducing antioxidant power (FRAP), DPPH scavenging activity and the
      ameliorative effects of the extracts on Fe2+-induced oxidative injury was
      investigated both in vitro and ex vivo. Alpha glucosidase and pancreatic lipase
      inhibitory potentials of the extracts were examined in vitro, while the effects
      of the ethanol extract on abdominal glucose intake and muscle glucose uptake were
      determined in freshly harvested tissues ex vivo. The extracts were subjected to
      Gas Chromatography-Mass Spectrometry (GC-MS) analysis to identify their possible
      bioactive components. The ethanol extract showed the most potent FRAP and DPPH
      radical scavenging activities compared to other extracts. All extracts increased
      catalase and SOD activities, and GSH levels in oxidative pancreatic injury. Both
      ethanol and aqueous extracts exhibited remarkable enzyme inhibitory activities,
      which was significantly higher than ethyl acetate extract and acarbose but was
      not comparable to orlistat. The ethanol extract portrayed a dose-dependent
      inhibitory effect on jejunal glucose uptake and enhancement of muscle glucose
      uptake. 9-(4 methoxyphenyl) xanthene, xanthone and stigmasterol showed strong
      binding affinities for alpha-glucosidase and lipase enzymes tested. Data from
      this study suggest that aerial parts of B. diffusa (particularly the ethanol
      extract) may not only exhibit antioxidant potentials but may also mediate anti
      lipidemic and anti-hyperglycemic effects via inhibiting fat and carbohydrate
      digestion as well as abdominal glucose intake and enhancing muscle glucose
      uptake.

PMID- 30119179
TI  - Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in
      bone marrow-derived mesenchymal stem cells in vivo.
AB  - Senescence has become a hot point issue in recent decades and requires urgent
      attention. As a novel and effective antioxidant, hydrogen has been proved to
      alleviate cellular senescence in endothelial cells in vitro. However, the effects
      and mechanisms of hydrogen on senescence in vivo are still unclear. In the
      present study, 12-month-old Sprague Dawley (SD) rats were intraperitoneal
      administration of hydrogen-rich saline (HRS, 10 ml/kg). Subsequently, bone marrow
      derived stem cells (BMSCs) were harvested for the detection of hydrogen
      antisenescence effects and mechanisms. The results showed that the number of
      senescence-associated beta-galactosidase (SA-beta-Gal) positive cells was reduced
      in BMSCs from rats treated with HRS. BMSCs in rats treated with HRS possessed a
      better proliferation ability, showed more effectively tri-lineage differentiation
      potential, and had less percentage of cells in G1 cell cycle arrest than the
      control cells. Additionally, HRS administration inhibited the production of
      intracellular reactive oxygen species (ROS) and decreased the expression of
      senescence-related proteins p53 and p21. Our results revealed that hydrogen could
      alleviate cellular senescence in vivo. And the underlying mechanism of
      antisenescence effects of hydrogen in BMSCs was via the ROS/p53/p21 signaling
      pathway. Thus, hydrogen could be a new and convenient strategy for alleviating
      senescence and for therapy of age-related diseases.

PMID- 30119180
TI  - Exosome-mediated miR-200b promotes colorectal cancer proliferation upon TGF-beta1
      exposure.
AB  - Exosome are emerging mediators of intercellular communication. Cancer-secreted
      exosome has an effect on the exosome donor cells and support cancer growth and
      metastasis. Here, we examine the TGF-beta1, a multifunctional cytokine involved
      in the regulation of cellular signaling pathways in human cancers, significantly
      contributes to upregulate miR-200b in exosome from colorectal cancer cell lines.
      The miR-200b enriched in exosome can be transferred into a new target cell to
      facilitating the colorectal cancer cells proliferation. Further studies showing
      that the exosomal miR-200b could directly target 3'-UTRs of p27 and RND3 resulted
      in knockdown of respective target proteins in recipient cells. Remarkably, the
      overexpression of p27/kip1 in HCT-116 cell, not RND3, resulted in effectively
      inhibited cell proliferation which induced by exosomal miR-200b. Moreover, animal
      experiment studies also confirmed a stimulating effect of exosomal miR-200b on
      colorectal cancer cell-derived xenografts. The expression p27/kip1 have decreased
      in tumors xenografts after injected with exosomal miR-200b. Our observations
      offer an evidence that whereby exosomal specific miRNA could amplify the
      proliferative element into the neighboring or distant cells to effective tumor
      growth.

PMID- 30119181
TI  - Clerodendrum volubile inhibits key enzymes linked to type 2 diabetes but induces
      cytotoxicity in human embryonic kidney (HEK293) cells via exacerbated oxidative
      stress and proinflammation.
AB  - The toxicity and safety associated with the use of medicinal plants remains a
      major concern. In this study, the antidiabetic properties of the dichloromethane
      (DCM) fraction of C. volubile leaves were investigated in vitro. Its cytotoxic
      effect and mechanism of toxicity were also investigated in Human Embryonic Kidney
      (HEK293) cells. The fraction was subjected to in vitro antioxidant assays using
      the 2,2'-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Ferric reducing
      antioxidant power (FRAP) protocols. Its enzyme-inhibitory properties were
      investigated on alpha-glucosidase and alpha-amylase activities. Gas
      Chromatography Mass Spectroscopy (GCMS) and Fourier Transform Infrared (FTIR)
      spectroscopic analysis were used to identify its phytoconstituents. Cytotoxicity
      was determined via MTT assay. The treated cells were assayed for reduced
      glutathione (GSH), non-protein thiol, nitric oxide and malondialdehyde (MDA)
      levels, as well as Superoxide Dismutase (SOD), catalase, myeloperoxidase and
      ATPase activities. Cell apoptosis and/or morphological changes were determined
      using the acridine orange and ethidium bromide (AO/EB) dual staining method. The
      fraction showed significant (p < 0.05) antioxidant and enzyme-inhibitory
      activity. It showed significant (p < 0.05) cytotoxic effect against HEK293 cells
      with concomitant depletion of antioxidative and elevation of proinflammatory
      biomarkers. Morphological changes were examined in the cells with an apoptotic
      index of 0.84. 1,1-Dodecanediol, diacetate was identified as the most predominant
      compound, while aromatics and amines as the most functional groups present in the
      fraction. These results suggest the antidiabetic and cytotoxic effects of C.
      volubile leaves. The toxicity can be attributed to induced oxidative stress and
      proinflammation with concomitant depletion of ATP leading to apoptosis of the
      cells.

PMID- 30119182
TI  - Gypenosides reverses depressive behavior via inhibiting hippocampal
      neuroinflammation.
AB  - Gypenosides, a saponins extract isolated from the Gynostemma pentaphyllum plant,
      produces neuroprotective effects in the brain. Our previous studies have shown
      that hippocampal glucocorticoid receptor (GR)-brain-derived neurotrophic factor
      (BDNF)-TrkB signaling was involved in the antidepressant-like effects of
      gypenosides. It remains unknown whether gypenosides could alleviate
      neuroinflammation in depressive-like animals. The aim of the present study was to
      address this issue in chronic unpredictable mild stress (CUMS). Gypenosides was
      administrated for four weeks, followed by sucrose preference test and tail
      suspension test, which were performed to evaluate the effects of gypenosides. The
      results showed that gypenosides reversed both the decreased sucrose preference
      and increased immobility time in CUMS mice. In addition, gypenosides also
      attenuated the increase of pro-inflammatory cytokine levels in the hippocampus of
      CUMS animals. Furthermore, the activation of NF-kappaB, as well as its upstream
      mediators IKKalpha and IKKbeta were inhibited by gypenosides. Last but not the
      least, CUMS promoted the activation of microglia, while gypenosides suppressed it
      according to the reduced number of iba1 positive cells. In conclusion, this study
      demonstrates that gypenosides exhibits the antidepressant-like effects in mice,
      which may be mediated by the inhibition of microglia and NF-kappaB signaling in
      the hippocampus.

PMID- 30119183
TI  - Ameliorative effects of indomethacin at different concentrations on endothelial
      insulin resistance through two distinct pathways.
AB  - Indomethacin (IDMT), a non-selective inhibitor of cycloxygenase-2 (COX-2), plays
      important roles in anti-inflammation and analgesia and it is commonly used to
      treat the patients with rheumatic and rheumatoid arthritis. Besides, various
      literatures reported that IDMT is a synthetic ligand of peroxisome proliferator
      activated receptor gamma (PPARgamma). Rosiglitazone (RSG), an insulin-sensitizer,
      is also a synthetic ligand and applied clinically to cure the patients with type
      2 diabetes mellitus. However, up to date little is known about whether IDMT
      ameliorates endothelial insulin resistance (IR). Accordingly, the purpose of this
      study is to investigate the effects of IDMT on endothelial IR and its underlying
      mechanism. Our present results showed that IDMT improved the endothelial IR
      induced by high glucose and fat concentration (HG/HF) in a concentration and time
      dependent manner. Intriguingly, we further identified that 0.25 mM of IDMT
      noticeably induced the expression levels of PPARgamma, AKT and endothelial nitric
      oxide synthase (eNOS) but failed to notably reverse the increases in expression
      levels of COX-2, inhibitory kappaB kinase (IKK) and tumor necrosis factor alpha
      (TNFalpha) induced by HG/HF; whereas 1.0 mM of IDMT exerted opposite effects
      compared with 0.25 mM of IDMT. Therefore, we conclude that IDMT ameliorates the
      endothelial IR induced by HG/HF through two distinct pathways, i.e., a lower
      concentration of IDMT through a PPARgamma-AKT-eNOS pathway while a higher
      concentration mainly via an IKK-COX-2/TNFalpha pathway. The findings might
      provide a novel clinical use for IDMT to cure IR-related disorders.

PMID- 30119184
TI  - Scoparone prevents IL-1beta-induced inflammatory response in human osteoarthritis
      chondrocytes through the PI3K/Akt/NF-kappaB pathway.
AB  - Osteoarthritis (OA) is a degenerative joint disease that is commonly accompanied
      by inflammation. Scoparone is a biologically active constituent isolated from
      Artemisia capillaris and possesses anti-inflammatory activity. However, the
      effect of scoparone on inflammatory response in OA has not been authenticated.
      The aim of this study was to evaluate the role of scoparone in OA in vitro. Our
      results showed that IL-1beta treatment significantly inhibited the cell viability
      of chondrocytes, whereas the inhibition effect was attenuated by scoparone in a
      dose-dependent manner. IL-1beta also efficiently induced the production of nitric
      oxide (NO), prostaglandin E2 (PGE2), MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in
      chondrocytes. However, scoparone dose-dependently suppressed the induction. In
      addition, scoparone repressed IL-1beta-induced the expression of iNOS and COX-2
      in chondrocytes. Furthermore, the activation of the PI3K/Akt/NF-kappaB pathway
      induced by IL-1beta was diminished by scoparone treatment. Taken together, these
      findings indicated that scoparone inhibited the expression of inflammatory
      mediators in IL-1beta-induced chondrocytes via regulating the PI3K/Akt/NF-kappaB
      pathway. Thus, scoparone may be used as a new therapeutic agent for the treatment
      of OA.

PMID- 30119185
TI  - Astilbin inhibits high glucose-induced autophagy and apoptosis through the
      PI3K/Akt pathway in human proximal tubular epithelial cells.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage renal disease. It has
      been found that astilbin, a flavonoid compound, exerts a protective effect on DN.
      However, the role of astilbin in autophagy during DN is unknown. The human
      proximal tubular epithelial cells (HK-2 cells) were treated with high glucose
      (HG, 30 mM) in the presence or absence of astilbin. Cell viability was measured
      by MTT assay. The autophagy was determined by detecting the expression of LC3-II
      and p62 using western blot. The cell apoptosis was evaluated by detecting the
      apoptosis rate, caspase-3 activity, and the expression of Bcl-2 and Bax. The
      expression levels of protein kinase B (Akt) and p-Akt were detected by western
      blot. To determine whether the phosphatidylinositol-3-kinase (PI3K)/Akt pathway
      was involved in the effect of astilbin, cells were treated with the inhibitor of
      Akt, LY294002. We found that astilbin (10 and 20 MUM) did not affect the
      viability of HK-2 cells, but attenuated HG-induced cell viability. Astilbin
      attenuated HG-induced autophagy and apoptosis in HK-2 cells. The expression of p
      Akt was inhibited by HG treatment, while the inhibitory effect of HG was
      attenuated by astilbin. Inhibition of the PI3K/Akt signaling resisted the effect
      of astilbin on HG-induced apoptosis and autophagy. In conclusion, astilbin
      attenuated HG-induced autophagy and apoptosis in HK-2 cells through the PI3K/Akt
      pathway. The results indicated that astilbin might be a new therapeutic agent and
      be useful for improving clinical management of DN.

PMID- 30119186
TI  - Effect of dual mTOR inhibitor on TGFbeta1-induced fibrosis in primary human
      urethral scar fibroblasts.
AB  - BACKGROUND: TGFbeta1 and mTOR are considered to play important roles in fibrotic
      diseases. Rapamycin has been reported to inhibit urethral stricture formation in
      a rabbit model of urethral fibrosis. AIM: To evaluate if dual mTOR inhibitor has
      a superior efficacy compared with rapamycin on inhibiting cell proliferation and
      collagen expression in human urethral scar fibroblasts (HUSFs). METHODS: We
      established HUSF cultures from fresh surgical specimen. The HUSFs were identified
      with typical fibroblast markers using immunofluorescence. Then we examined the
      effect of TGFbeta1 on HUSFs using Cell Counting Kit-8 and Western blot. The
      inhibiting effects of OSI-027 (a dual mTOR inhibitor) on cell proliferation and
      collagen expression in TGFbeta1-induced HUSFs were compared with rapamycin using
      Cell Counting Kit-8, Western blot, and quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR). RESULTS: HUSFs were stained positive for
      vimentin, collagen I, and collagen III. TGFbeta1 had no effect on cell
      proliferation but increased collagen I and collagen III expressions in HUSFs. OSI
      027 was more effective inhibiting cell proliferation and collagen expression
      compared with rapamycin in TGFbeta1-induced HUSFs. OSI-027 played a more
      important role in inhibiting TGFbeta1-induced mTOR pathway and phosphorylation of
      Smad2 compared with rapamycin in HUSFs. CONCLUSION: OSI-027 can inhibit the pro
      fibrotic effects of TGFbeta1 significantly compared with rapamycin in HUSFs.
      These findings may provide a new therapy in the adjunctive treatment of urethral
      stricture disease.

PMID- 30119188
TI  - Antioxidant and apoptotic effects of Callistemon lanceolatus leaves and their
      compounds against human cancer cells.
AB  - Callistemon lanceolatus (Myrtaceae) has been utilized in folk medicine and its
      pharmacological properties are widely studied. Phytochemicals are effectively
      recognized as bases of pharmacologically potent drugs for the development of
      anticancer therapeutics. The free radical scavenging potential of numerous
      extracts of C. lanceolatus leaves, Hexane leaf extract (HLE), Chloroform leaf
      extract (CLE), Ethyl acetate leaf extract (ELE), Methanol leaf extract (MLE), and
      Aqueous leaf extract (ALE)) were determined by Biochemical assay. We evaluated
      the anticancer activity of C. lanceolatus leaves extracts against different human
      cancer cell lines viz liver cancer cells (HepG2), breast cancer cells (MCF7), and
      normal human embryonic kidney (HEK 293) cell line. The ELE and MLE extracts of C.
      lanceolatus leaves showed potential antiproliferative effects on HepG2 cells. On
      the basis of free radical scavenging potential and cytotoxicity studies, ELE and
      MLE extracts of C. lanceolatus leaves are further evaluated in detail for
      numerous biological activities. ELE and MLE extracts reduced the cell growth, ROS
      generation, lowering the potential of cell migration and inhibits the metastatic
      activity in HepG2 cell lines. ELE and MLE extracts treated HepG2 cells showed
      down-regulation of STAT3 and up-regulation of p53 and inhibition of cdk2 and
      cyclin A activity. Phytochemicals analysis have shown that the ELE and MLE
      possess some anticancer compounds like 4-Fluoro-2-trifluoromethylbenzoic acid,
      neopentyl ester; fumaric acid, di(pent-4-en-2-yl) ester; 2,3-Dihydro-3,5
      dihydroxy-6-methyl-4H-pyran-4-one and 2-Furancarboxaldehyde,5-(hydroxymethyl).
      Molecular docking results demonstrate that interactions of compounds present in
      ELE and MLE extracts with the SH2 domain of STAT3, might be responsible for their
      inhibitory effects. We have further concluded that the ELE and MLE extracts of C.
      lanceolatus arrests the cells at S and G2/M phase and subsequently induced cell
      death by regulating the DNA damage in HepG2 cells.

PMID- 30119187
TI  - Protective effect of Rotula aquatica Lour against gentamicin induced oxidative
      stress and nephrotoxicity in Wistar rats.
AB  - Gentamicin is an aminoglycoside antibiotic widely used for the treatment of life
      threatening infections caused by Gram-negative bacteria. The use of gentamicin
      was limited due to its ototoxic and nephrotoxic adverse effects. The current
      study was designed to evaluate the protective effect of ethyl acetate fraction
      from Rotula aquatica (EFRA) against gentamicin induced nephrotoxicity. The
      antioxidant enzymes status, lipid peroxidation, nitrate and ROS level, serum
      markers like creatinine, Urea, BUN were estimated in the present study. The
      histopathological analysis of renal tissues was done by H&E and PAS staining. The
      mRNA level expression of KIM-1, NF-kappaB, TNF- alpha, and IL-6 were measured by
      semi-quantitative reverse transcription-polymerase chain reaction. The changes in
      antioxidant parameters were restored by the treatment of EFRA at different dose
      (50 mg/kg bwt, 100 mg/kg bwt). The serum parameters, ROS, MDA and nitrate level
      were decreased by administration of EFRA. The EFRA ameliorates histological
      changes associated with gentamicin induced nephrotoxicity. The mRNA level
      expression of KIM-1, NF-kappaB, TNF- alpha, and IL-6 were downregulated in EFRA
      treated groups. The results from present study reveals the role of EFRA as good
      anti-inflammatory and nephro protective drug.

PMID- 30119189
TI  - Royal jelly increases peripheral circulation by inducing vasorelaxation through
      nitric oxide production under healthy conditions.
AB  - AIMS: Royal jelly (RJ) has a variety of reported biological activities, including
      vasorelaxation and blood pressure-lowering effects. Although functional foods are
      positively used for health, the effects of RJ on the cardiovascular system in
      healthy individuals have not been well studied. Therefore, we investigated the
      mechanisms underlying the vasorelaxation effects of RJ in healthy control rats to
      evaluate whether the peripheral circulation was increased. MAIN METHODS: We used
      fresh RJ to examine the vasorelaxation effects and related mechanisms in Wistar
      rats using organ bath techniques. Furthermore, we measured changes in tail blood
      circulation, systolic blood pressure (sBP), and heart rate (HR) after the oral
      administration of RJ to control rats and nitro-l-arginine methyl ester (l-NAME)
      treated rats (0.5 mg/ml dissolved in distilled drinking water for 1 week).
      Concentrations of acetylcholine (ACh) in the RJ were measured using a commercial
      kit. KEY FINDINGS: RJ caused vasorelaxation of isolated rat aortas and superior
      mesenteric arteries, and this effect was inhibited by atropine (10-5 M, 15 min)
      or L-NAME (10-4 M, 20 min) and endothelium-denuded arterial ring preparations.
      Oral RJ increased tail blood flow and mass in control rats 1 h after treatment
      without affecting velocity, sBP, or HR. These effects were not observed in L-NAME
      treated rats. RJ contained approximately 1000 MUg/g of ACh. SIGNIFICANCE: The
      present study demonstrated that RJ is composed of muscarinic receptor agonist(s),
      likely ACh, and induces vasorelaxation through nitric oxide (NO) production from
      the vascular endothelium of healthy rats, leading to increased tail blood
      circulation. Thus, fresh RJ may improve peripheral circulation in healthy
      individuals.

PMID- 30119190
TI  - LncRNA FOXD2-AS1 regulates chondrocyte proliferation in osteoarthritis by acting
      as a sponge of miR-206 to modulate CCND1 expression.
AB  - Recently, accumulating evidence demonstrated that the long non-coding RNAs
      (lncRNAs) play important roles in osteoarthritis (OA) progression. However, the
      role of lncRNA FOXD2-AS1 on OA is still unclear. In the present study, qRT-PCR
      showed that expression of FOXD2-AS1 and Cyclin D1 (CCND1) was upregulated in OA
      cartilage tissues, while miR-206 expression was significantly decreased. CCK-8
      and colony formation assays showed that FOXD2-AS1 could promote chondrocytes
      viability. Flow cytometry analysis showed that FOXD2-AS1 inhibition arrested
      chondrocytes in G0/G1 phase and induced cells apoptosis. Furthermore, luciferase
      reporter assay and RIP assay showed that FOXD2-AS1 could function as a sponge of
      miR-206. Rescue assays showed that miR-206 inhibitors reversed the effects of
      FOXD2-AS1 suppression on chondrocytes viability. In addition, we identified that
      CCND1 acted as a direct target of miR-206. FOXD2-AS1 suppression could inhibit
      CCND1 expression in chondrocytes, while miR-206 inhibitors reversed CCND1
      expression. Moreover, rescue assays indicated that CCND1 overexpression reversed
      the effects of FOXD2-AS1 suppression on chondrocytes viability. Taken together,
      these data indicated that FOXD2-AS1 could promote the growth of chondrocytes by
      targeting miR-206/CCND1 axis.

PMID- 30119191
TI  - A preclinical overview of metformin for the treatment of type 2 diabetes.
AB  - Type 2 diabetes (T2D) is the most common type of diabetes mellitus and is mainly
      characterized by insulin resistance, beta-cell dysfunction, and elevated hepatic
      glucose output. Metformin is a first-line antihyperglycemic agent that works
      mainly by regulating hepatic glucose production and peripheral insulin
      sensitivity. Metformin has been clinically applied for more than half a century,
      although the underlying pharmacological mechanisms remain elusive. This current
      review mainly focused on the development history of metformin and related
      preclinical studies on structural modification, pharmacological mechanisms for
      treatment of T2D, toxicology, pharmacokinetics, and pharmaceutics. The
      pharmacological function of metformin in lowering hyperglycemia suggests that
      multi-targeting could be an effective strategy for the discovery of new anti
      diabetic drugs. A number of discoveries have revealed the pharmacologic
      mechanisms of metformin; however, precise mechanisms remain unclear. Deeper
      investigations on the biological features of metformin are expected to provide
      more rational applications and indications of this evergreen anti-T2D agent,
      which will in turn help to better understand the complicated pathogenesis of T2D.

PMID- 30119192
TI  - Puerarin promoted proliferation and differentiation of dopamine-producing cells
      in Parkinson's animal models.
AB  - BACKGROUND: Parkinson's disease (PD) is caused by the gradual loss of dopamine
      producing cells in the brain. This study evaluated the potential neuroprotective
      role of puerarin (PR) on dopamine (DA)-producing cells in vitro and in vivo.
      METHOD: In vitro, the effects of PR on proliferation and differentiation and DA
      releases of mesenchymal stem cells (MSCs) were assayed by CCK-8, flow cytometry,
      real-time PCR and ELISA respectively. Then the differentiated cells were labeled
      with enhanced green fluorescent protein (EGFP) and administrated into PD animal
      models induced by 6-OHDA. The proliferation and differentiation of labeled cells
      were identified by fluorescence microscopy and immunostaining. RESULTS: In vitro,
      after being treated with different concentrations of PR for 1 week, the TUJ1, TH
      and DAT protein and mRNA expression and DA releases increased significantly. In
      vivo, after transplantation of PR-treated DA-producing cells, the symptoms of PD
      improved significantly from the second week after transplantation; more
      transplanted cells survived and migrated to wider region along injection line;
      more transplanted cells proliferated and differentiated into TH+ cells; more DA
      was detected in the striatum during 6 weeks' observation. CONCLUSION: The results
      suggest that PR promote DA neuron survival, proliferation and differentiation.

PMID- 30119193
TI  - LncRNA THOR acts as a retinoblastoma promoter through enhancing the combination
      of c-myc mRNA and IGF2BP1 protein.
AB  - Long non-coding RNA (lncRNA) THOR is an extremely conserved lncRNA with
      specifically expressed in testis while widespreadly exist in human multiple
      cancer tissues. The high expression of it significantly promotes the occurrence
      and progression of melanoma, non-small cell lung cancer, osteosarcoma and renal
      cell carcinoma. However, the expression pattern and effects of lncRNA THOR in the
      progression of retinoblastoma remain unclear. As a result, this study was
      conducted to discovery the expression and roles of lncRNA THOR in the malignant
      phenotype transformation of retinoblastoma cells, as well as its underlying
      mechanism. Our results demonstrated that lncRNA THOR was over-expressed in the
      retina tissues from retinoblastoma patients and retinoblastoma Y79 and WERI-Rb1
      cell lines. Down-regulation of lncRNA THOR with siRNA significantly repressed
      cell growth, migration and S phase accumulation, while induced cell apoptosis and
      G1 phase reduction and reduced the expression of c-myc. Besides, knockdown of c
      myc promoted cell apoptosis and suppressed cell proliferation. Furthermore, RNA
      pull down and PIP assays showed that up-regulation of lncRNA THOR enhanced the
      combination of IGF2BP1 protein and c-myc RNA. And lncRNA THOR up-regulation
      obviously increased the tumorigenesis of Y79 cells in vivo. In conclusion, this
      study makes clear that lncRNA THOR is up-regulated in retinoblastoma, and its
      over-expression significantly enhances the malignant phenotype transformation of
      retinoblastoma cells through up-regulating c-myc expression via enhancing its
      combination with TGF2BP1 protein. Overall, our study illustrates that lncRNA
      THOR/c-myc molecular cascade might be another potent target for retinoblastoma
      treatment.

PMID- 30119194
TI  - The protective effect of formononetin on cognitive impairment in streptozotocin
      (STZ)-induced diabetic mice.
AB  - The present study was aimed to elucidate the pharmacological effect of
      Formononetin (FMN) treatment on STZ-induced diabetic cognitive dysfunction. The
      diabetic model was induced by an intraperitoneally injection of 180 mg/kg STZ.
      The animals were randomly divided into five groups: control group, streptozocin
      (STZ, 180 mg/kg) group, STZ + metformin (Met, 200 mg/kg) group, STZ + FMN (25
      mg/kg) group, STZ + FMN (50 mg/kg) group. The mice were intragastrically
      administrated with metformin (Met, 200 mg/kg) or FMN (25, 50 mg/kg) once daily
      for 6 weeks. The blood glucose content and body weight were examined. Morris
      water maze test and Y maze test were used to evaluate the learning and memory
      abilities. The cognitive decline was reversed by regulating superoxide dismutase
      (SOD), malondialdehyde (MDA), tumor necrosis factor-a (TNF-alpha),
      interleukin(IL)-1beta, IL-6 in serum and hippocampus. The protein expressions of
      high mobility group box-1 protein (HMGB1), toll like receptor 4 (TLR4), myeloid
      differentiating factor 88 (MyD88), inhibitor of NF-kappaB (IkappaBalpha), p
      IkappaBalpha, nuclear factor kappa-B(NF-kappaB), p-NF-kappaB, NOD-like receptor
      3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC) and
      caspase-1 were detected. Furthermore, the SH-SY5Y cells were exposed to high
      glucose stimulation, FMN (2.5, 5 and 10 MUM) treatment, and glycyrrhizin, the
      selective inhibitor of HMGB1. After an incubation for 22 h, the SH-SY5Y cells
      were harvested for detection. As a result, FMN treatment effectively attenuated
      the body weight, learning and memory abilities, as well as the levels of blood
      glucose, SOD, MDA, TNF-alpha, IL-1beta, IL-6. FMN administration also
      downregulated the protein expressions of HMGB1, TLR4, MyD88, p-IkappaB, p-NF
      kappaB, NLRP3, ASC and caspase-1. The inhibition of HMGB1 by glycyrrhizin also
      confirmed the involvement of HMGB1/TLR4/NF-kappaB/NLRP3 pathway in high glucose
      induced SH-SY5Y cells. In summary, the results suggested that FMN exhibited the
      protective effect on STZ-induced cognitive impairment possibly via the mediation
      of HMGB1/TLR4/NF-kappaB signaling and NLRP3 inflammasome.

PMID- 30119195
TI  - Sevoflurane reduced functional connectivity of excitatory neurons in prefrontal
      cortex during working memory performance of aged rats.
AB  - BACKGROUND: Sevoflurane has been found to increase apoptosis and pathologic
      markers associated with Alzheimer disease, provoking concern over their potential
      contribution to postoperative cognitive dysfunction. This study aimed to evaluate
      the effects of sevoflurane on working memory of rats and to characterize
      functional connectivity between excitatory neurons in the prefrontal cortex (PFC)
      during working memory performance. METHODS: 18-month-old and 3-month-old male SD
      rats were implanted with a multielectrode array in the PFC. After recovery from
      the surgery, the aged and adult rats were divided into sevoflurane group and
      control group, respectively. Rats in sevoflurane group were exposed to 1 minimum
      alveolar concentration (MAC) or 1.5 MAC sevoflurane for two hours. At day1, 3,
      and 7 after exposure, the effects of sevoflurane anesthesia on working memory
      were investigated in the aged and adult rats by using delayed alternation in Y
      maze. Spike trains of excitatory neurons in the PFC were recorded with the
      multielectrode array while rats were undergoing working memory performance.
      Functional connectivity between PFC excitatory neurons was described by Granger
      causal connectivity analysis. RESULTS: In adult rats, 1.5 MAC sevoflurane reduced
      working memory and functional connectivity between PFC excitatory neurons at day1
      after exposure (P < 0.01). However, in aged rats, 1.5 MAC sevoflurane reduced
      working memory and functional connectivity between PFC excitatory neurons at
      day1, 3, and 7 after exposure (P < 0.01). 1 MAC sevoflurane reduced working
      memory and functional connectivity between PFC excitatory neurons of aged rats at
      day1 after exposure (P < 0.01), but it had no effect in adult rats. CONCLUSIONS:
      Sevoflurane-induced working memory impairment may depend on advanced age and
      anesthetic concentration. These findings also suggest, in rats, that sevoflurane
      induced working memory impairment may be related to the decreased functional
      connectivity between PFC excitatory neurons.

PMID- 30119196
TI  - Determination of gliclazide minimum concentration in type 2 diabetes mellitus
      patients.
AB  - Type 2 diabetes mellitus is a worldwide health problem. Many drugs can be used in
      its treatment. One of them is gliclazide - the sulfonylurea derivative. It is
      dosed in modified release tablets. The study aimed to determine the minimum
      steady-state concentration of gliclazide at patients taking modified release
      tablets. Fasting plasma glucose, insulin level, and glycated hemoglobin were also
      assayed in this study. Ten patients of the primary care physician clinic took 30
      90 mg of gliclazide daily. The statistical analysis proved that there is a
      statistically significant correlation between insulin level and body weight (p =
      0.044) as well as between the dose and gliclazide concentrations (p = 0.015) and
      also between insulin level and minimum concentration of the drug (p = 0.0074).
      The linear correlation between dose and gliclazide's minimum steady state
      concentration proved its linear pharmacokinetics. The correlation between the
      minimum concentration of gliclazide and insulin level might be a potential
      predictor of patients compliance.

PMID- 30119197
TI  - Tauroursodeoxycholic acid alleviates hepatic ischemia reperfusion injury by
      suppressing the function of Kupffer cells in mice.
AB  - The aim of this study is to investigate the protective effect and the mechanism
      of tauroursodeoxycholic acid (TUDCA) against hepatic ischemia reperfusion (IR)
      injury. Male Balb/c mice were intraperitoneally injected with
      tauroursodeoxycholic acid (400 mg/kg) or saline solution, once per day for 3 days
      before surgery, and then the model of hepatic I/R injury was established. Blood
      and liver samples were collected from each group at 3, 6, and 24 h after surgery.
      Liver pathological changes, liver function, hepatocyte apoptosis and
      proinflammatory factors were detected. KCs were extracted, cultured and treated
      with TUDCA or phosphate-buffered saline (PBS) for 24 h, and then viability and
      phagocytosis were examined. Additionally, IRE1alpha/TRAF2/NF-kappaB pathway
      activity and AML cell apoptosis were detected. The results showed that TUDCA
      alleviated hepatic I/R injury, the level of liver function markers, and
      hepatocyte apoptosis in vivo. Furthermore, the proinflammatory effects of KCs
      were suppressed by down-regulating IRE1alpha/TRAF2/NF-kappaB pathway activity in
      vivo. TUDCA dose-dependently suppressed the expression of inflammatory factors
      and IRE1alpha/TRAF2/NF-kappaB pathway activity in vitro, consistent with the in
      vivo results. Therefore, TUDCA can effectively alleviate hepatic IR injury by
      down-regulating the activity of the IRE1alpha/TRAF2/NF-kappaB pathway to suppress
      the function of KCs.

PMID- 30119198
TI  - Emerging novel drug delivery strategies for bioactive flavonol fisetin in
      biomedicine.
AB  - Fisetin (FIS), a bioactive flavonol found in the smoke tree (Cotinus coggygria),
      vegetables, fruits and nuts. It exhibits various therapeutic activities such as
      anti-oxidant, anti-inflammatory, anti-invasive, anti-tumorigenic, anti
      angiogenic, anti-diabetic, cardioprotective and neuroprotective activities. In
      spite of the ever rising support for therapeutic activities, its clinical
      application is mainly limited because of poor water solubility, high
      lipophilicity and low oral bioavailability. Till date, numerous efforts have been
      made to surpass these limitations with the development of new improved delivery
      platforms. This article aims to review and analyze the various delivery
      strategies used to improve the biopharmaceutical properties of FIS. Furthermore,
      an attempt has been made to touch upon various features related to the progress
      of drug delivery including their influence on FIS chemistry, pharmacokinetics and
      other physicochemical attributes are discussed thoroughly.

PMID- 30119199
TI  - The mechanistic insight of polyphenols in calcium oxalate urolithiasis
      mitigation.
AB  - About 12% of world population is affected by different forms of urolithiasis of
      which the recurrence rate in female is 47-60% and in male is 70-80%. Standard
      therapeutic agents (allopurinol, citrate, cystone and thiazide diuretics) are
      used to prevent and treat urolithiasis but these are not universally-effective
      due to common kidney stone relapse and other side effects. Surgical treatment
      causes long-term renal damage, hypertension and stone recurrence. Polyphenols,
      the plant-derived bioactive molecules, have showed protection against cancers,
      cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases,
      among a number of other ailments. The role of these phytochemicals in
      urolithiasis management is emerging. Hence, the present review discusses peer
      reviewed published literature till date on this aspect and highlights that
      polyphenols could effectively inhibit the formation of calcium oxalate urinary
      stones (most common renal stone), correlating with their antioxidant, anti
      inflammatory, diuretic and angiotensin-converting enzyme (ACE) inhibition.
      Further, we have proposed the prospects and challenges in developing the plant
      polyphenols into drugs against kidney stone prevention. This review might be a
      stepping stone for further investigation into the clinical implications of the
      polyphenols in urolithiasis remediation.

PMID- 30119200
TI  - Xanthohumol induces apoptosis via caspase activation, regulation of Bcl-2, and
      inhibition of PI3K/Akt/mTOR-kinase in human gastric cancer cells.
AB  - We assessed the effect of xanthohumol (XN) on gastric cancer (GC) in vitro and in
      vivo. XN reduced the viability of SGC-7901, SNU216, and SNU668 cells, but not GES
      1 non-tumorigenic human gastric epithelial cells. XN induced apoptosis in SGC
      7901 cells in a concentration-dependent manner by enhancing the numbers of late
      and early apoptotic cells. XN also downregulated the anti-apoptotic proteins Bcl
      XL and Bcl-2 and upregulated the pro-apoptotic proteins Bax, Bid, PARP, and
      caspase-3. XN induced phosphorylation of PI3K, Akt, and mTOR in SGC7901 cells.
      Also, XN reduced the tumour volume and weight by inhibiting the phosphorylation
      of Akt and mTOR. XN-treated tumours had significantly fewer proliferating cells
      and more apoptotic cells compared with the control. Our data indicate that XN
      induces apoptosis of human GC cells in vivo. Thus, XN may have potential as an
      anti-GC agent.

PMID- 30119201
TI  - Synergistic antitumour effects of triptolide plus gemcitabine in bladder cancer.
AB  - BACKGROUND AND OBJECTIVE: Gemcitabine (GEM) effectively inhibits bladder cancer
      progression in the clinic, but novel combination treatments using multiple drugs
      are needed. MATERIALS AND METHODS: The bladder cancer cell lines EJ and UMUC3
      were treated with triptolide (TPL) and/or GEM. Tumour cell viability and
      proliferation were measured using MTT and clonogenic assays, respectively. Flow
      cytometry and western blotting were used to detect the cell cycle phase,
      apoptosis, reactive oxygen species (ROS) and the levels of specific relevant
      proteins. The AKT/GSK3beta signalling pathway proteins were also measured by
      immunofluorescence and western blotting. RESULTS: The cytotoxicity of the GEM
      plus TPL combination treatment was stronger than that of GEM or TPL alone. In
      bladder cancer cell lines, GEM plus TPL induced cell cycle arrest at the G1 phase
      via suppression of CDK4, CDK6 and cyclins A1 and A2. Significantly increased
      apoptosis and increases in apoptosis-related proteins (caspase 8 and Bcl-xL) were
      observed in cells treated with GEM plus TPL. While ROS increased, certain ROS
      related proteins (catalase and SOD2) clearly decreased in cells treated with a
      combination of GEM plus TPL. The AKT/GSK3beta signalling pathway was also
      inhibited more significantly in cells treated with the GEM plus TPL combination
      than in cells treated with either agent alone. CONCLUSION: The combination of GEM
      plus TPL showed significantly enhanced anticancer effects compared to those of
      GEM or TPL alone.

PMID- 30119202
TI  - Ximenia americana heteropolysaccharides ameliorate inflammation and visceral
      hypernociception in murine caerulein-induced acute pancreatitis: Involvement of
      CB2 receptors.
AB  - BACKGROUND: This study aimed to investigate and characterize the anti
      inflammatory and anti-hypernociceptive effects of the total polysaccharides of X.
      americana (TPL-Xa) bark in a mouse model of acute pancreatitis-induced by
      caerulein and the potential involvement of cannabinoid receptors. METHODS: TPL-Xa
      was characterized by1H and 13C NMR spectroscopy. Animals received TPL-Xa (10
      mg/kg, i.v.) 30 min before and after caerulein (50 MUg/kg, 10*, i.p.)
      administration. To evaluate the involvement of cannabinoid receptors, AM281 (3
      mg/kg, s.c.) and AM630 (1 mg/kg, s.c.) were administered 30 min before TPL-Xa.
      Plasma levels of amylase and lipase, pancreatic myeloperoxidase (MPO), histology,
      visceral hypernociception and motor coordination were evaluated 11 and 24 h after
      acute pancreatitis (AP) induction. RESULTS: TPL-Xa, containing a
      heteropolysaccharide composed of glucose, galactose, arabinose, rhamnose, fucose
      and galacturonic acid, reduced amylase and lipase levels, MPO activity, acinar
      cell necrosis, edema and neutrophil infiltration. TPL-Xa increased the threshold
      of visceral hypernociception, an effect reversed by AM630, an antagonist of
      cannabinoid receptor type 2 (CB2). In addition, TPL-Xa did not alter the animals'
      motor coordination. CONCLUSIONS: TPL-Xa contains heteropolysaccharides that
      inhibit inflammation and hypernociception in the experimental model of caerulein
      induced AP, by a mechanism involving type CB2 receptors.

PMID- 30119203
TI  - Apocynin inhibited NLRP3/XIAP signalling to alleviate renal fibrotic injury in
      rat diabetic nephropathy.
AB  - AIMS: In this animal study, we tried to test the hypothesis that apocynin could
      play an anti-inflammation role by inhibiting NLRP3/X-linked inhibitor of
      apoptosis protein (XIAP) signalling and have an effect on antifibrosis in rats
      with diabetic nephropathy. MAIN METHODS: Diabetic nephropathy rats were induced
      by tail-vein injection of streptozotocin at 60 mg/kg body weight in sodium
      citrate buffer (0.01 M, pH 4.5) with unrestricted access to food/water for 12
      weeks, and rats with blood glucose levels above 18.0 mM were considered diabetic;
      the damage index for glomerular mesangial cells damage index was calculated by
      morphological examinations; protein and mRNA changes were analysed by western
      blotting immunohistochemistry and real-time quantitative polymerase chain
      reaction; interstitial fibrosis was assessed and scored using Masson's staining.
      KEY FINDINGS: In rats with diabetic nephropathy, apocynin (1) reduced renal
      injury and improved renal function; (2) downregulated the expression of NLRP3 in
      renal cortex; (3) downregulated the expression of XIAP in renal cortex; and (4)
      attenuated renal fibrosis. SIGNIFICANCE: As an inhibitor of reactive oxygen
      species (ROS), apocynin could downregulate the expression of NLRP3 and XIAP, and
      alleviate renal fibrosis, which meant not only that ROS was one type of ligands
      of NLRP3, but also that ROS mechanism and NLRP3 activation might be therapeutic
      targets in the treatment of diabetic nephropathy in the future.

PMID- 30119204
TI  - Yu Gan Long reduces rat liver fibrosis by blocking TGF-beta1/Smad pathway and
      modulating the immunity.
AB  - Yu Gan Long (YGL) is a Chinese traditional herbal medicine that has been used in
      the treatment of liver fibrosis for many years in clinical practice. However, its
      anti-hepatofibrotic mechanism has not been studied yet. In this study, the effect
      and mechanism of YGL in reducing liver fibrosis was demonstrated in vivo. Our
      results showed that liver fibrosis biomarkers collagen IV (Col IV), type III
      precollagen (PCIII), hyaluronuc acid (HA) and laminin (LN), were increased after
      CCl4 treatment and decreased by YGL. Among the liver fibrosis indicators, alpha
      smooth muscle actin (alpha-SMA) was decreased by YGL in the CCl4-treated rats,
      while MMP2 and MMP9 was upregulated followed by TIMP1 downregulation. Proteins
      involved in liver fibrosis such as p-Smad2, p-Smad3 and Smad4 were down
      regulated, while Smad7 protein was up-regulated by YGL after CCl4-induced liver
      damage. YGL also suppressed the increase of TGF-beta1, TNF-alpha, IL-1beta, IL-6,
      IL-4 and IL-17 A induced by CCl4 treatment, while promoted IFN-gamma expression.
      Finally, the transcription factors ROR-gammat and GATA3 were decreased, while T
      bet was increased after YGL treatment. These results suggested that YGL
      attenuated CCl4-induced hepatic fibrosis by accelerating the extracellular matrix
      degradation, blocking the TGF-beta1/Smad signaling pathway and modulating the
      balance among IL-4, IL-17 A and IFN-gamma, demonstrating YGL protective effect
      and its potential mechanisms in treating liver fibrosis.

PMID- 30119205
TI  - Theabrownin suppresses in vitro osteoclastogenesis and prevents bone loss in
      ovariectomized rats.
AB  - Drinking tea exhibits beneficial effects on bone health and may protect against
      osteoporosis, particularly in postmenopausal women. Theabrownin (TB) is the main
      component responsible for the biological activities of Pu-erh tea, but whether it
      possesses anti-osteoporotic potential remains unknown. Here we investigated the
      in vitro and in vivo anti-osteoporotic effects of TB in the RAW 264.7 cell line
      and ovariectomized (OVX) rats, respectively. Our in vitro studies showed that TB
      significantly suppressed RANKL-induced osteoclastogenesis and the expression of
      related marker proteins, including NFATc1, TRAP, c-Fos, and cathepsin K. In vivo
      studies showed that TB treatment effectively ameliorated blood biochemical
      parameters, organ weights and organ coefficients in OVX rats. In addition, TB
      treatment significantly improved femoral bone mineral density (BMD) and
      biomechanical properties. What's more, TB treatment strikingly ameliorated bone
      microarchitecture in OVX rats because of increased cortical bone thickness and
      trabecular bone area in the femur. Our study therefore demonstrated that TB can
      inhibit RANKL-induced osteoclastogenesis in vitro and prevent bone loss in
      ovariectomized rats. Consequently, TB has a promising potential in postmenopausal
      osteoporosis treatment.

PMID- 30119206
TI  - Down-regulation of Rictor enhances cell sensitivity to PI3K inhibitor LY294002 by
      blocking mTORC2-medicated phosphorylation of Akt/PRAS40 in esophageal squamous
      cell carcinoma.
AB  - PI3K/Akt/mTOR signaling pathway plays a vital role in regulating cell survival,
      differentiation, metabolism and migration, which is frequently hyperactive in a
      number of cancers, including esophageal squamous cell carcinoma (ESCC). As the
      core subunit of mTORC2, Rictor is shown to be amplified in ESCC patients' tissues
      and plays an important role in regulation of Akt. The objective of this study is
      to evaluate the effects of Rictor knockdown on cell sensitivity to PI3K inhibitor
      LY294002 in ESCC cells and ESCC xenografts as well as its mechanisms. We found
      LY294002 obviously restrained cell proliferation in dose-dependent and time
      dependent manners by inhibiting PI3K/Akt/mTOR/p70S6K signaling pathway, whereas
      triggered mTORC2-medicated phosphorylation of Akt (Ser473)/PRAS40 (Thr246) in
      ECa109 and EC9706 cells. Stable knockdown of Rictor by shRNA enhanced the
      inhibitory effects of LY294002 on cell proliferative, migration and colony
      formation, as well as promoted its effects on cell cycle arrest and cell
      apoptosis in vitro. Furthermore, stable knockdown of Rictor enhanced the
      antitumor effects of LY294002 by inhibiting tumor growth and promoting cell
      apoptosis in vivo. Mechanistic assay revealed that knockdown of Rictor could
      attenuate LY294002-induced phosphorylation of Akt (Ser473)/PRAS40 (Thr246). Our
      results provide rationale that combined inhibition of Rictor/mTORC2 and PI3K for
      the treatment of ESCC.

PMID- 30119207
TI  - MiR-1294 confers cisplatin resistance in ovarian Cancer cells by targeting IGF1R.
AB  - BACKGROUND: Dysregulation of miRNAs is critical for chemosensitivity to platinum
      based agents in ovarian cancer (OC) which is the most aggressive gynecological
      cancer. However, the underlying mechanisms of miRNA-regulated platinum resistance
      in ovarian cancer remain unclear. In this study, we intended to investigate the
      effect of miR-1294 on platinum-resistant OC. METHODS: The expression of miR-1294
      in OC tissues (n = 30) and cell lines was measured by qRT-PCR. Cell transfection
      was carried out to establish miR-1294 overexpression or knockdown. MTT and clone
      formation assays were performed to examine proliferation in OC cells.
      Additionally, wound healing and tumor invasion assays were used to investigate
      cell migration and invasion, respectively. Finally, the expression of epithelial
      to-mesenchymal transition (EMT)-associated proteins was measured in OC cells by
      western blot. RESULTS: Our results showed that miR-1294 dysregulation manipulated
      OC cisplatin resistance through regulating IGF1R. Knockdown of IGF1R decreased
      SKOVP/DDP cell proliferation, migration, invasion and EMT. Moreover,
      overexpression of miR-1294 prevented OC cisplatin resistance. CONCLUSION: Our
      results indicated that epigenetic regulation of IGF1R via miR-1294 was essential
      for cisplatin resistance in OC and provide a new avenue for OC treatment.

PMID- 30119208
TI  - Exendin-4 inhibits glioma cell migration, invasion and epithelial-to-mesenchymal
      transition through GLP-1R/sirt3 pathway.
AB  - GLP-1 analogue exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist
      which shares 53% sequence with GLP-1, plays an essential role in human tumors.
      However, the function and mechanisms underlying the effects of exendin-4 on
      glioma cell migration, invasion and epithelial-to-mesenchymal transition are
      still obscure. Firstly, we demonstrated that GLP-1R was expressed in all glioma
      cell lines including U87, U251, U373 and A172. Exendin-4 treatment inhibited
      glioma cell survival, proliferation, migration and invasion. Also, exendin-4
      inhibited epithelial-to-mesenchymal transition through positively regulating the
      expression of E-cadherin (epithelial marker), and negatively regulating the level
      of Vimentin (mesenchymal marker). Interestingly, we next demonstrated that
      exendin-4 elevated sirt3 expression dependent on the high level of GLP-1R in U87
      and 251 cells. Finally, we confirmed that depletion the level of GLP-1R or sirt3
      both reversed the inhibitory action of exendin-4 on glioma cell migration and
      invasion. These findings demonstrate that exendin-4 treatment suppressed the
      migration and invasion of glioma cells through GLP-1R/sirt3 pathway and exendin-4
      plays an inhibitory effect on glioblastoma cell migration and invasion.

PMID- 30119209
TI  - MiR-92a promotes tumorigenesis of colorectal cancer, a transcriptomic and
      functional based study.
AB  - Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide.
      Accumulation of varieties of epigenetic changes, including miRNA regulation, is
      one of the fundamental processes driving CRC initiation and progression. Mir-92a
      has been reported in several studies as an oncogene, and particularly in
      colorectal cancer, it has become a useful biomarker for early detection of CRC in
      both serum or stool. The Cancer Genome Atlas (TCGA) is a powerful database to
      analyze cancer-related genes and their correlation with patients' pathological
      information. However, miR-92a expression and its regulating target genes has yet
      to be investigated in TCGA system. In this study, we found miR-92a expression is
      associated with CRC pathological process. Notably, high expression of miR-92a
      mainly occurs in microsatellite-stable (MSS) cases. Further experiments showed
      exogenous introduction of miR-92a into LoVo and SW480 cells could enhance cell
      proliferation, migration, and invasion, whereas inhibition of miR-92a showed the
      opposite effects. A system analysis based on binding capacity and expression
      correlation analysis confirmed DKK3 and KLF4 are the top target genes of miR-92a,
      and novel target SMAD7 highlights the role of miR-92a in BMPs/SMAD pathway. In
      conclusion, miR-92a acts as an oncomir and directly targets Wnt/beta-catenin,
      PTEN/Akt/FoxO, and BMP/Smads related genes, thus participates in CRC progression.

PMID- 30119210
TI  - Phytochemical constituents and pharmacological properties of Garcinia
      xanthochymus- a review.
AB  - The purpose of this study was to determine the phytochemical constituents and
      pharmacological properties of Garcinia xanthochymus which is commonly known as
      gamboge, yellow mangosteen and false mangosteen. The phytochemicals constituents,
      pharmacological benefits and their mechanisms were previously presented in a
      number of studies including in vitro and in vivo studies from published books,
      journals and articles. The literature used in this review were published between
      1970 and 2017 and were available from databases such as Google Scholar,
      ScienceDirect, Scopus, PubMed, ProQuest and others. The chemical structures in
      this paper are drawn using ChemBio Ultra 14.0. G. xanthocymus contains many
      phytochemicals that can be extracted from its constituent parts; the bark,
      fruits, leaves, roots, twigs and seeds. The predominant extracted phytochemicals
      are xanthones, benzophenones, flavonoids, depsidones and isocoumarins. These
      phytochemicals contribute to the pharmacological activities of this plant as an
      antioxidant, antidiabetic, and for having Nerve Growth Factor-potentiating,
      antimicrobial and cytotoxic activities. This species contains a broad range of
      phytochemicals with curative properties that can be greatly beneficial to man.
      Notably, this review focused on those studies of the pharmacological effects of
      this plant that were concentrated on by previous researchers. Thus, further study
      needs to be done on G. xanthocymus in order to unlock additional potential
      activities and to pinpoint the exact mechanisms of how these activities can be
      induced, leading to new drug discoveries which have fewer side effects.

PMID- 30119211
TI  - Anti-hypertrophy effect of atorvastatin on myocardium depends on AMPK activation
      induced miR-143-3p suppression via Foxo1.
AB  - Left ventricular hypertrophy (LVH) is a pathological characteristic shared by
      distinct heart disorders. Atorvastatin is employed as a lipid lowering agent and
      its heart protection effect has been recently reported as well. Thus, the current
      study attempted to validate the anti-hypertrophy effect of atorvastatin as well
      as the associated mechanism. Hypertrophic feature was induced in rats using
      transverse aortic constriction (TAC) method and in cardiomyocytes using
      angiotensin II (Ang II). Then the animals and cells were treated with
      atorvastatin and the effect on cardiac weight and structure as well as cell
      viability, surface area, and apoptosis was assessed. The mechanism associated
      with the anti-hypertrophy effect of atorvastatin was further explored by focusing
      on the AMPK/Foxo1/miR-143-3p axis. The results showed that the administration of
      atorvastatin significantly suppressed TAC-induced heart weight increase and
      attenuated cardiac structure deteriorations in rats. In in vitro assays,
      atorvastatin increased cell viability, and reduced cell surface area and
      apoptosis in Ang II-treated H9c2 cells. At molecular level, atorvastatin
      activated AMPK, which further promoted Foxo1 activation and suppressed miR-143-3p
      level. The key role of AMPK during atorvastatin treatment was further validated
      by subjecting Ang II-treated H9c2 cells to co-incubation of atorvastatin and
      Compound C, which blocked the pro-survival and anti-hypertrophy effect of
      atorvastatin on H9c2 cells. The findings outlined in the current study confirmed
      the anti-hypertrophy effect of atorvastatin and provided a preliminary
      explanation on the mechanism associated with the treatment: the protective effect
      of atorvastatin on myocardium against hypertrophy depended on miR-143-3p
      inhibition via AMPK and Foxo1 activation.

PMID- 30119212
TI  - Silencing of cytoskeleton-associated protein 2 represses cell proliferation and
      induces cell cycle arrest and cell apoptosis in osteosarcoma cells.
AB  - Osteosarcoma is the most common primary bone malignancy, mainly occurring in
      children and adolescents. Cytoskeleton-associated protein 2 (CKAP2), which plays
      important roles in cell proliferation, has been reported to be overexpressed in
      diverse human cancers. In the present study, we aimed at exploring the expression
      and functions of CKAP2 in osteosarcoma. The mRNA and protein expression of CKAP2
      was analyzed on collected osteosarcoma and control bone cyst tissues. The results
      indicated that CKAP2 expression was remarkably elevated in osteosarcoma tissues
      compared with bone cysts tissues. The expression level of CKAP2 in osteosarcoma
      was associated with overall survival, tumor size and tumor stage. In addition,
      down-regulation of CKAP2 by RNA interference in osteosarcoma cell lines, MG63 and
      SW1353, caused a remarkable inhibition in cell proliferation in vitro and
      xenograft growth in nude mice. Silencing of CKAP2 also significantly induced
      G0/G1 arrest and cell apoptosis of osteosarcoma cells. Furthermore,
      phosphorylation levels of Janus kinase 2 (JAK2) and Signal transducers and
      activators of transcription 3 (STAT3) were significantly reduced in CKAP2
      knockdown cells. The expression of downstream targets of JAK2/STAT3 signaling,
      Cyclin D1, Bcl-2 and survivin, was also decreased in CKAP2 knockdown cells. Such
      aberrations can be rescued by re-expression of RNAi-resistant CKAP2.
      Collectively, the present study indicates that CKAP2 is a potential oncogene by
      targeting JAK2/STAT3 signaling, and that CKAP2 may serve as a novel target for
      osteosarcoma therapy.

PMID- 30119213
TI  - Xuebijing injection induces anti-inflammatory-like effects and downregulates the
      expression of TLR4 and NF-kappaB in lung injury caused by dichlorvos poisoning.
AB  - BACKGROUND: The mechanism in lung injury caused by acute organophosphate
      pesticide poisoning (AOPP) and an effective treatment remains unclear. We aim to
      clarify how the inflammatory lung injury caused by AOPP might be modulated by
      Xuebijing (XBJ) injection. METHODS: AOPP-induced lung injury model was induced by
      dichlorvos (DDVP) subcutaneous administration in rats and XBJ injection was
      administered by intraperitoneal injection after DDVP challenge. The effects of
      XBJ injection were assessed by lung histopathological analysis and lung injury
      scores, lung wet-to-dry weight ratios (WDR) and oxygenation, differential immune
      cell count in bronchoalveolar lavage fluid (BALF), IL-6 and TNF-alpha levels in
      blood, the levels of TLR4 and NF-kappaB proteins in lung tissue and blood
      acetylcholinesterase (AChE) activity. RESULTS: DDVP administration resulted in
      damage of lung histopathology and lower PaO2/FiO2 ratios (P < 0.05), which were
      notably attenuated by XBJ injection (P < 0.05). Total cell, macrophage, and
      neutrophils count in BALF and TNF-alpha and IL-6 levels in blood were
      significantly increased after DDVP exposure (P < 0.05), which were notably
      ameliorated by XBJ injection (P < 0.05). TLR4 and NF-kappaB protein in lung
      tissue expression after DDVP challenge were markedly increased (P < 0.05), and
      they were substantially downregulated by XBJ injection (P < 0.05). In addition,
      blood AChE activity was significantly decreased by DDVP administration (P <
      0.05), however, there was no significant improvement after XBJ injection.
      CONCLUSION: XBJ injection prevents DDVP poisoning induced lung injury by
      attenuating the inflammatory response. The protective effect appears to be
      mediated through downregulation of the TLR4 and NF-kappaB expression.

PMID- 30119214
TI  - The pleiotropic role of interleukin-17 in atherosclerosis.
AB  - Atherosclerosis is the main cause of cardiovascular diseases (CVDs), which
      considers the leading cause of mortality worldwide. Atherosclerosis is a chronic
      inflammatory condition of arterials' wall in which the development and the
      destabilization of plaque occur. Both innate and adaptive immunity play a
      significant role in modifying lipoproteins in arterials' wall. Recent
      investigations have demonstrated the opposing roles of CD4+ T cells subtypes in
      atherosclerosis. T helper-1 (Th1) response and pro-inflammatory cytokines possess
      proatherogenic effects, whereas T regulatory (Treg) cells have an
      atheroprotective role. Th17 cells have emerged as a new CD4+ T-cell subtype,
      which produce IL-17 that plays a crucial role in numerous inflammatory and
      autoimmune diseases. Recently, several studies have investigated the potential
      role of IL-17 in atherosclerosis. Some investigations have suggested a
      proatherogenic effect, however the others proposed an atheroprotective role.
      Hence, the exact role of IL-17 in the disease development and plaque stability is
      still debatable. In this review, we summarize the current knowledge on both
      atherogenesis and atheroprotective roles of IL-17. In addition, the synergistic
      and antagonistic effects of IL-17 with other cytokines in atherosclerosis will be
      discussed. On the basis of the current understanding of these roles, the
      possibility of developing novel therapeutic strategies against atherosclerosis
      may be evolved.

PMID- 30119215
TI  - MAPK8 mediates resistance to temozolomide and apoptosis of glioblastoma cells
      through MAPK signaling pathway.
AB  - OBJECTIVE: In this study, we aimed to evaluate the expression and functions of
      MAPK8 in temozolomide (TMZ) -resistant glioblastoma cells as well as to explore
      the mechanism of TMZ resistance in glioblastoma cells. METHODS: Gene Expression
      Omnibus (GEO) database was used for identifying the differentially expressed
      genes (DEGs) in TMZ resistant samples. The functional partner genes of TMZ were
      screened out by Gene-drug interaction network (STITCH) and the glioblastoma
      related genes were selected by gene search engine with evidence sentences
      (Digsee). The interactions among identified DEGs and glioblastoma-related genes
      were detected by Search Tool for the Retrieval of Interacting Genes (STRING). The
      dysregulated pathways were identified by Gene set enrichment analysis (GSEA). qRT
      PCR was performed to detect the expression level of MAPK8 in glioblastoma cells.
      Western blot was used to detect the expressions of MAPK8 and MAPK signaling
      pathway-related proteins. MTT assay was utilized to measure the cell viability of
      TMZ sensitive and resistant cells. Colony formation assay was performed to detect
      the clone ability and flow cytometry (FCM) assay was applied to identify the
      apoptosis rate of TMZ resistant glioblastoma cells. RESULTS: MAPK8 was one of the
      DEGs and was up-regulated in TMZ resistant glioblastoma cells. The MAPK signaling
      pathway was activated in TMZ resistant glioblastoma cells under the condition of
      over-expression of MAPK8. The inhibition of MAPK8 restrained the colony
      formation, inducing apoptosis of TMZ resistant glioblastoma cells and suppressed
      the MAPK signaling pathway. CONCLUSION: MAPK8 promoted the resistance to TMZ,
      accelerated cell proliferation and inhibited the apoptosis of glioblastoma cells
      via activating MAPK signaling pathway.

PMID- 30119216
TI  - Withaferin-A attenuates multiple low doses of Streptozotocin (MLD-STZ) induced
      type 1 diabetes.
AB  - Type 1 diabetes mellitus (T1DM) is one of the major metabolic disorders with life
      long dependence on insulin. The present study was designed to evaluate the
      antioxidant and anti-diabetic potential of Withaferin A (WA), the active
      constituent of Withania somnifera in multiple low doses of Streptozotocin (MLD
      STZ) induced T1DM. STZ (40 mg/Kg) was administered intraperitoneally (i.p.) for 5
      consecutive days to male Swiss albino mice to induce T1DM. Mice were concurrently
      treated with WA (2 & 10 mg/Kg). Blood glucose levels, intraperitoneal glucose
      tolerance test, oxidative stress parameters were estimated biochemically (MDA,
      GSH) and immunohistochemically (Nrf2, NFkappaB). In addition, inflammatory
      cytokines, and insulin levels were quantified by ELISA method. Apoptosis was
      assessed by immunohistochemical staining for cleaved-caspase-3 and TUNEL assay.
      WA treatment significantly reduced the blood glucose levels and improved glucose
      clearance. Strikingly, we observed a significant reduction in the incidence of
      diabetes upon WA treatment and only 2 out of 8 (2/8 = 25%) animals were diabetic.
      WA ameliorated the MLD-STZ induced oxidative and nitrosative stress. Furthermore,
      WA exhibited promising anti-inflammatory effect as evident from reduction in the
      levels of IL-6 (p < 0.05) and TNF-alpha (p < 0.05) compared to diabetic mice. In
      addition, insulitis scoring and IHC for Nrf2 and NFkappaB indicated promising
      anti-diabetic effect. WA reduced MLD-STZ induced DNA fragmentation and apoptosis,
      further supporting the observed protective effect. We, to the best of our
      knowledge, report for the first time that WA can effectively combat MLD-STZ
      induced T1DM via modulation of Nrf2/NFkappaB signaling and holds substantial
      potential for therapy of T1DM.

PMID- 30119217
TI  - Long noncoding RNA OIP5-AS1 accelerates CDK14 expression to promote osteosarcoma
      tumorigenesis via targeting miR-223.
AB  - The critical roles for long non-coding RNAs (lncRNAs) have been demonstrated for
      series of cancers, including osteosarcoma. Nevertheless, the accurate mechanism
      of lncRNAs in osteosarcoma is elusive. In this assay, mechanical researches are
      performed to investigate the effect and mechanism of lncRNA OIP5-AS1 in
      osteosarcoma tumorigenesis. Results revealed that OIP5-AS1 level was elevated in
      osteosarcoma tissue and cells. Clinically, OIP5-AS1 high-expression was closely
      correlated with osteosarcoma patients' poor prognosis. Mechanistically, silenced
      OIP5-AS1 expression significantly repressed the proliferative ability and
      accelerated the apoptosis, meanwhile triggered G0/G1 phase cycle arrest in vitro
      and mice neoplasm growth in vivo. Subsequently, miR-223 was predicted to target
      the 3'-UTR of OIP5-AS1 and constituted RNA induced silencing complex, which was
      confirmed by RNA immunoprecipitation and luciferase reporter assay. Besides, miR
      223 targeted the CDK14 mRNA 3'-UTR. In conclusion, our study found the critical
      regulation of OIP5-AS1/miR-223/CDK14 axis on osteosarcoma tumorigenesis,
      indicating the tumor promoting role of OIP5-AS1 for osteosarcoma.

PMID- 30119218
TI  - Histamine H1 type receptor antagonist loratadine ameliorates oxidized LDL induced
      endothelial dysfunction.
AB  - Oxidized LDL (ox-LDL) is one of the major risk factors of atherosclerosis.
      Endothelial dysfunction caused by ox-LDL is an early event in the pathogenesis of
      cardiovascular diseases. Preclinical studies have been performed to explore
      efficient means of preventing endothelial abnormalities. In this study, we
      revealed that loratadine, a histamine H1 type receptor specific antagonist,
      possesses a protective effect by relieving ox-LDL-induced endothelial
      inflammation. Treatment of endothelial cells with ox-LDL induces expression of
      the H1 receptor. The presence of loratadine in endothelial culture efficiently
      suppressed ox-LDL-induced attachment of monocytes to endothelial cells,
      production of ROS and vascular adhesion molecules, and induction cytokines
      including VCAM-1, E-selectin, TNF-alpha, IL-6 and IL-8. Mechanistically, we show
      that loratadine potently blocks ox-LDL-induced JNK activation as well as the AP-1
      and NF-kappaB signaling pathways. Collectively, our data disclose a new role for
      loratadine in endothelial protection.

PMID- 30119219
TI  - Long non-coding RNA NORAD upregulate SIP1 expression to promote cell
      proliferation and invasion in cervical cancer.
AB  - Long non-coding RNAs (lncRNAs) play important roles in tumor progression.
      Recently, increasing evidence showed that lncRNA NORAD could be used as an
      important regulator in tumor progression. However, the roles and underlying
      mechanism of NORAD in cervical cancer (CC) remain unclear. In the present study,
      we found that NORAD expression was significantly up-regulated in CC tissues and
      cell lines. High NORAD expression was correlated with advanced FIGO stage, lymph
      nodes metastasis, vascular invasion, and poor overall survival of CC patients. In
      vitro function assays, we showed that NORAD suppression reduced CC cells
      proliferation, invasion, and epithelial-mesenchymal transition (EMT) processes.
      Furthermore, the underlying mechanism studies showed that lncRNA NORAD could
      sponge miR-590-3p to promote the proliferation and invasion of CC cells via
      upregulating SIP1 expression. In addition, we showed that NORAD inhibition could
      reduce CC cells growth in vivo. Taken together, these results suggested that
      NORAD could serve as a ceRNA in CC progression by modulating miR-590-3p/SIP1 axis
      and act as a therapeutic target for the treatment of CC.

PMID- 30119220
TI  - Novel docetaxel chitosan-coated PLGA/PCL nanoparticles with magnified
      cytotoxicity and bioavailability.
AB  - In the present study, docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA)
      and polycaprolactone (PCL) nanoparticles were successfully prepared and coated
      with chitosan (CS). The prepared nanoparticles (NPs) were evaluated for their
      particle size, zeta potential, particle morphology, drug entrapment efficiency
      (EE%), and in vitro drug release profile. The anticancer activity of DTX-loaded
      NPs was assessed in human HT29 colon cancer cell line utilizing MTT assay. The
      pharmacokinetics of DTX-loaded NPs was monitored in Wistar rats in comparison to
      DTX solution. The prepared NPs exhibited particle sizes in the range 177.1 +/-
      8.2-287.6 +/- 14.3 nm. CS decorated NPs exhibited a significant increase in
      particle size and a switch of zeta potential from negative to positive. In
      addition, high EE% values were obtained for CS coated PCL NPs and PLGA NPs as
      67.1 and 76.2%, respectively. Moreover, lowering the rate of DTX in vitro release
      was achieved within 48 h by using CS coated NPs. Furthermore, a tremendous
      increase in DTX cytotoxicity was observed by CS-decorated PLGA NPs compared to
      all other NPs including DTX-free-NPs and pure DTX. The in vivo study revealed
      significant enhancement in DTX bioavailability from CS-decorated PLGA NPs with
      more than 4-fold increase in AUC compared to DTX solution. In conclusion, CS
      decorated PLGA NPs are a considerable DTX-delivery carrier with magnificent
      antitumor efficacy.

PMID- 30119221
TI  - Prunetin inhibits lipopolysaccharide-induced inflammatory cytokine production and
      MUC5AC expression by inactivating the TLR4/MyD88 pathway in human nasal
      epithelial cells.
AB  - Allergic rhinitis (AR) is a chronic upper respiratory disorder characterized by
      inflammation of the nasal mucosa. Prunetin is an O-methylated isoflavone, which
      has been found to possess anti-inflammatory activity. The aim of the current
      study was to evaluate the effect of prunetin on inflammatory cytokine and mucus
      production and its underlying mechanism in nasal epithelial cells. Results showed
      that treatment with prunetin (10, 30, and 50 MUM) inhibited lipopolysaccharide
      (LPS)-induced expression and secretion of interleukin (IL)-6, IL-8, and mucin 5
      AC (MUC5 AC) in RPMI2650 cells, and attenuated the effect of LPS on toll-like
      receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88)
      expression. TAK-242 (an inhibitor of TLR4) treatment or TLR4 knockdown attenuated
      LPS-induced expression and secretion of IL-6, IL-8 and MUC5 AC. In conclusion,
      prunetin inhibited LPS-induced inflammatory cytokine production and MUC5 AC
      expression and secretion by inactivating the TLR4/MyD88 pathway in human nasal
      epithelial cells. These results suggested that prunetin might be a useful agent
      in the treatment of AR.

PMID- 30119222
TI  - ADMA, homocysteine and redox status improvement affected by 7-nitroindazole in
      spontaneously hypertensive rats.
AB  - Inhibition of nitric oxide (NO) production can influence blood pressure
      regulation and increase hypertension. Asymmetric dimethylarginine, ADMA, an
      analogue of L-arginine, can inhibit NO synthesis, impair endothelial function,
      and is a risk marker of cardiovascular diseases. Homocysteine (Hcy) level affects
      oxidative stress production of reactive oxygen species (ROS) in hypertension and
      also influences changes in signaling and cell damage. The present study was
      focused on experimental effects of exogenous NOS inhibitors and their effect on
      ADMA, an endogenous NOS inhibitor, homocysteine and ROS production measured as
      reactive oxidative metabolites (ROM). We compared effects of the two potential
      exogenous NO-inhibitors: NG-nitro L-arginine methyl ester (L-NAME) and 7
      nitroindazole (7-NI). Levels of ADMA, Hcy, ROM and total thiols (TTL) were not
      changed in the L-NAME group. With 7-NI administration, we observed unchanged NOS
      activity in the left ventricle and a pronounced decrease of ADMA and Hcy levels,
      accompanied by ROM over-production in plasma. TTL/ROM ratio was more favorable
      than in the L-NAME group. We observed that 7-NI, an exogenous NOinhibitor, can
      decrease and improve the levels of ADMA, Hcy, and ROM, and increase TTL/ROM ratio
      in the plasma of spontaneously hypertensive rats.

PMID- 30119223
TI  - Neuroprotective role of fucoxanthin against cerebral ischemic/reperfusion injury
      through activation of Nrf2/HO-1 signaling.
AB  - In the present study, an attempt was made to determine whether administration of
      fucoxanthin could attenuate cerebral ischemic/reperfusion (I/R) injury and its
      possible mechanisms using an in vivo middle cerebral artery occlusion (MCAO)
      model and an in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) model.
      Fucoxanthin was intragastrically administrated in different doses (30 mg/kg, 60
      mg/kg, and 90 mg/kg, respectively) to the rats 1 h before MCAO induction. The
      neurological function, infarct area and brain water content of rats were then
      evaluated. Rat cortical neuron were pretreated with different doses of
      fucoxanthin (5 MUM, 10 MUM, and 20 MUM) and then subjected to OGD/R. Expression
      levels of proteins in the brain tissues and cultured cells were determined by
      western blotting. Our results demonstrated that fucoxanthin pretreatment improved
      the neurologic deficit score, lowered the infarct volume and reduced the
      expression of apoptosis-associated proteins in brain tissues. In addition,
      fucoxanthin also suppresses OGD/R-induced apoptosis and ROS accumulation in
      cultured neurons. Furthermore, we found that fucoxanthin could significantly
      activate the Nrf2/HO-1 signaling through inducing Nrf2 nuclear translocation with
      enhanced HO-1 expression, and Nrf2 knockdown obviously abrogated the beneficial
      role of fucoxanthin in OGD/R-treated neurons. These findings suggested that
      fucoxanthin could be exploited as a therapeutic target for protecting neurons
      from cerebral I/R injury.

PMID- 30119224
TI  - The potential hepatoprotective effect of royal jelly against cadmium chloride
      induced hepatotoxicity in mice is mediated by suppression of oxidative stress and
      upregulation of Nrf2 expression.
AB  - This study was aimed at investigating the possible protective mechanism of royal
      jelly (RJ) against hepatotoxicity induced by cadmium chloride (CdCl2). The study
      included four groups: the control group received saline (0.9% sodium chloride),
      CdCl2 group received 6.5 mg/kg CdCl2 for seven days, RJ group received 85 mg/kg
      standardized RJ containing 6% 10-hydroxy-2-decenoic acid equivalent to 250 mg
      crude RJ, and finally, the fourth group received RJ 2 h before CdCl2 injection
      daily for 7 days. Oxidant/antioxidant markers of liver function estimation and
      histopathology were determined. The results revealed that RJ significantly
      ameliorated the hepatotoxic side effects of Cd. Furthermore, RJ inhibited
      oxidative stress, inflammation, and hepatic tissue injury; normalized enzymatic
      and nonenzymatic antioxidant molecules; and enhanced nuclear-related factor-2
      (Nrf-2) expression. Our results provide new insights into the hepatoprotective
      property of RJ and revealed that RJ prevented hepatic injury, oxidative stress,
      and inflammation by upregulating Nrf2 and the anti-apoptotic protein Bcl-2.
      Hence, RJ can be used as a hepatoprotective agent against the toxic effects of
      CdCl2.

PMID- 30119225
TI  - Application of nanoparticles in percutaneous delivery of active ingredients in
      cosmetic preparations.
AB  - Developments in nanotechnology have expanded novel nanoparticles for several
      applications, including cosmetic topical preparation. The aim of this article was
      to review recent literature on percutaneous delivery of cosmetics active
      ingredient by nanoparticles. The main focus here, is on lipid based nanoparticles
      since they are of great importance in skin cargo delivery and have vast
      application in current cosmetic formulations. Data were collected via electronic
      databases using MeSH keywords, including nanoparticles, lipid particles,
      cosmetic, dermal delivery and combinations of these words. According to
      literature nanoparticles play a major role in improving the usefulness of
      cosmetics. They are able to improve the physiochemical stability of the skin
      based cosmetic products. Based on data, lipid nanostructures can be added to
      current cosmetic formulations without any significant problem due to their
      physical stability and compatibility with other ingredients. However, due to
      their basically risky nature of nanoparticles, their risk assessment should be
      taken into consideration.

PMID- 30119226
TI  - Novel endodontic sealers induced satisfactory tissue response in mice.
AB  - OBJECTIVES: The aim of this study was to evaluate the subcutaneous response
      induced by Roeko Guttaflow2 (RG), Sealapex Xpress (SX), AH Plus (AHP) sealers.
      METHODS: 100 BALB/c mice received implants in the subcutaneous tissue with the
      tested materials (10 animals per period for each evaluated sealer) and were
      evaluated after different experimental periods (7, 21 and 63 days), in each
      animal was placed a tube, the control group was an empty tube. Histological
      analysis evaluated semi-quantitatively the inflammatory infiltration, collagen
      fiber formation and tissue thickness. In addition, immunohistochemistry was
      performed for interleukin-6 (IL-6). Data were statistically analyzed (alpha =
      0.05). RESULTS: RG promoted a greater collagen fiber formation at 7 days and 63
      days compared to the CG (p = 0.004) and AHP (p = 0.005) respectively, while at 21
      days, the SX promoted a greater reaction (p = 0.021). For the tissue thickness,
      there was a greater reaction at 7 days with CG (p = 0.0156) and with RG at 63
      days (p = 0.03). Regarding the inflammatory infiltrate, there was no difference
      at 7 days and 63 days (p = 0.5; p = 0.27), while at 21 days, a statistically
      difference was found between SX, CG (p = 0.04) and RG (p = 0.027). In addition,
      the presence of IL-6 was observed in almost all groups, with a more intense
      marking at 7days. SIGNIFICANCE: All cements evaluated presented a satisfactory
      tissue response, however, RG was the one that presented a more satisfactory
      tissue response.

PMID- 30119228
TI  - Phytochemicals, withaferin A and carnosol, overcome pancreatic cancer stem cells
      as c-Met inhibitors.
AB  - Receptor tyrosine kinases (RTKs) are pharmaceutically attractive targets due to
      their fundamental role in tumor formation. The hallmark of pancreatic cancer is
      its high mortality rate attributed to the existence of cancer stem cell (CSC)
      subpopulations which result in therapy resistance and recurrence. c-Met is a
      known pancreatic CSC marker that belongs to the family of RTKs. To surmount the
      hurdles related to ligand-independent c-Met activation, we aimed to elucidate the
      inhibitory mechanisms of withaferin A (WA) and carnosol (CA) as two hit
      phytochemicals against c-Met kinase domain. Both tested compounds attenuated HGF
      mediated proliferation across various established c-Met+ cancer cell lines and
      altered cell cycle distribution accompanied by apoptosis induction. Scratch assay
      confirmed the anti-migratory activity of WA and CA in AsPC-1 cells. The blockade
      of HGF-driven cellular growth and motility was reflected by the suppression of c
      Met phosphorylation and its downstream pro-survival pathway Akt. Further studies
      showed that the administration of WA and CA diminished the sphere-formation and
      clonogenic potential which was validated by down-regulation of pluripotency
      maintaining genes (oct-4 and nanog), demonstrating their potentiality to target
      pancreatic CSCs. As more than 60% of anti-cancer drugs are composed of natural
      product-derived inhibitors known as fourth generation inhibitors, our present
      data suggest that WA and CA may hold promise to eradicate CSCs in c-Met-dependent
      cancers.

PMID- 30119227
TI  - In vitro and in vivo anticancer efficacy potential of Quercetin loaded polymeric
      nanoparticles.
AB  - Quercetin (QCT) is a flavonoid, abundantly present in plants and has gained
      considerable interest for its antioxidant property and chemo preventive activity.
      Bioavailability of QCT is very low due to its poor aqueous solubility and
      instability. Researchers are working on the application of nanotechnology to
      target chemotherapeutic drugs to the tumour site. The aim of the present study
      was to develop quercetin loaded chitosan nanoparticles (QCT-CS NPs) with enhanced
      encapsulation efficiency and sustained release property. We prepared
      biocompatible NPs with small size (<200 nm) and encapsulation efficiency of
      79.78%. In vitro drug release study exhibited a cumulative amount of 67.28%
      release of QCT over a period of 12 h. at pH 7.4. In vitro cytotoxicity assay
      showed significantly reduced IC50 value of QCT-CS NPs as compared to free QCT (p
      < 0.05). Intra venous treatment of QCT-CS NPs in tumour xenograft mice with A549
      and MDA MB 468 cells exerted significant reduction of tumour volume in comparison
      to disease control groups (p < 0.05). Serum anti oxidant enzyme superoxide
      dismutase (SOD) level markedly increased in QCT-CS NPs treated tumour bearing
      mice than free QCT treated group. In summary, the recent investigations reported
      successful encapsulation of QCT in chitosan (CS) NPs to target the tumour
      microenvironment and exhibited enhanced efficacy of QCT-CS NPs in cancer therapy.

PMID- 30119229
TI  - The human papillomavirus (HPV)-related cancer biology: An overview.
AB  - Despite the novel diagnostic methods and therapies implemented in oncology, the
      number of patients that succumb by the cancer remains high globally. Currently
      studies point out that 20-25% of all human malignancies are related to micro
      organism infections. Among these cancer-related pathogens, the human
      papillomavirus (HPV) has a prominent position, since the virus is responsible for
      about 30% of all infectious agent-related cancers. Thus, an amount of cancers
      could be avoided by means prophylactic and/or therapeutic measures. However,
      these measures required a holistic comprehension about HPV-related cancer
      biology. Based on this, this review aims to summarize the last evidences of HPV
      on cancer biology (from initiation to metastasis), focus on molecular and
      biochemical deregulations associated with viral infection, and discuss the viral
      etiology in different malignancies.

PMID- 30119230
TI  - beta-elemene against Burkitt's lymphoma via activation of PUMA mediated apoptotic
      pathway.
AB  - Burkitt's lymphoma is a type of highly aggressive Non-Hodgkin's lymphoma.
      Although advanced Burkitt's lymphoma is responsive to high-intensity chemotherapy
      regimens, increasing systemic toxicity, tumor recurrence and metastasis
      significantly reduce the patient survival. Thus, it is important to investigate
      novel antitumor agents with safety and effectiveness. beta-elemene shows anti
      proliferative effect on cancer cells by triggering apoptosis through regulating
      several molecular signaling pathways. However, its role in the suppression of
      Burkitt's lymphoma has not yet been fully elucidated. The inhibitory effect of
      beta-elemene in Burkitt's lymphoma was studied in vitro and in vivo, as well as
      the involved molecular mechanism. The results demonstrated that beta-elemene
      effectively inhibited the growth and induced the apoptosis of Burkitt's lymphoma
      cells through upregulation of PUMA expression and modulating PUMA related
      apoptotic signaling pathway. The in vivo data confirmed the anti-tumor effect of
      beta-elemene in the xenografts, suggesting that beta-elemene is associated with
      PUMA activation, leading to Bax and caspase induction and onset of mitochondrial
      apoptosis.

PMID- 30119232
TI  - Long non-coding RNA FTH1P3 regulated metastasis and invasion of esophageal
      squamous cell carcinoma through SP1/NF-kB pathway.
AB  - : AIMS:: Recent research showed that Long non-protein coding RNA ferritin heavy
      chain 1 pseudogene 3 (FTH1P3) plays a crucial role in the course of tumor
      formation. The present study was aimed to explore its role in esophageal squamous
      cell carcinoma (ESCC). MAIN METHODS: Quantitative reverse transcriptase
      polymerase chain reaction (qRT-PCR) was used to examine the expression levels of
      FTH1P3, mRNA SP1 and NF-kB in ESCC samples and cell lines. The impact of FTH1P3
      knockdown was evaluated by WST-1 assays, colony formation assays, scratch wound
      assays, migration and invasion assays. KEY FINDINGS: FTH1P3 was significantly
      upregulated in ESCC tissues and cells (P < 0.001). Knockdown of FTH1P3 notably
      decreased the proliferation, migration, and invasion capacity of ESCC cells.
      Silencing of FTH1P3 decreased the expression of specificity protein 1 (Sp1) and
      NF-kB (p65) in EC9706 and EC1. SIGNIFICANCE: FTH1P3 plays a crucial role in ESCC
      tumorigenesis, and can be used as a potential therapeutic target for ESCC.

PMID- 30119231
TI  - Intestinal absorption mechanisms of araloside A in situ single-pass intestinal
      perfusion and in vitro Caco-2 cell model.
AB  - Araloside A is a triterpenoid saponin,which exhibits a broad spectrum of
      pharmacological activities, such as stimulating fibrinolysis, preventing
      coagulant, inhibiting renin, and decreasing blood pressure. Our previous report
      found that the compound exhibits a poor absolute bioavailability. However the
      underlying mechanisms of its absorption have not been investigated in the small
      intestine or in a Caco-2 cell model. In this study, the absorption mechanisms of
      araloside A were investigated in a Caco-2 cell monolayer and in a single-pass
      intestinal perfusion in situ model with Sprague-Dawley rats. The effects of basic
      parameters, such as compound concentration, time, temperature, paracellular
      pathway, different intestinal segments were analyzed, and the susceptibility of
      araloside A absorption process to treatment with various inhibitors, such as the
      P-gp inhibitor verapamil, the multidrug resistance protein2 inhibitors (MRP2)
      MK571 and indomethacin, the breast cancer resistance protein (BCRP) inhibitors
      Ko143 and reserpine, and endocytosis inhibitor chlorpromazine were assessed. It
      can be found that the mechanisms of intestinal absorption of araloside A may
      involve multiple transport pathways, such as passive diffusion, the paracellular
      pathway, as well as the participation of efflux transporters.

PMID- 30119233
TI  - Ursolic acid loaded intra nasal nano lipid vesicles for brain tumour:
      Formulation, optimization, in-vivo brain/plasma distribution study and
      histopathological assessment.
AB  - The aim was to formulate an optimized ursolic acid (UA) loaded lipid vesicle
      using formulation by design approach (FbD) for improving the drug targeting by
      nasal route for brain tumor. Three factors were evaluated at three different
      levels using anethole (terpene) (A), ethanol (B) and phospholipid90 G (C) as
      independent variables and their individual and combined effects were observed for
      PDI (Y1), vesicle size (Y2) and encapsulation efficiency (Y3) to select an
      optimal system (UALVopt). The optimized formulation was further converted into
      gel and evaluated for drug release, nasal permeation study, brain/plasma uptake
      and histopathology study. The UALVopt formulation containing anethole as terpene
      (1% as A), ethanol (2.6% as B) and phospholipid90 G (8.8 mg as C) showed low PDI
      (0.212), vesicle size (115.56 nm) and high entrapment efficiency (76.42%). The in
      vitro drug release and ex-vivo permeation study results revealed prolonged drug
      release and permeation. The brain/blood ratio for UALVGopt remained significantly
      higher at all the time points with respect to UALVopt indicating higher and
      prolonged retention of drug at site of action. The histopathological study of the
      nasal mucosa and brain confirmed non-toxic nature of developed formulation. The
      formulation UALVGopt could serve as a better alternative for the brain targeting
      via the intranasal route which in turn could subsequently improve its efficacy.

PMID- 30119234
TI  - Current trends and emerging diagnostic techniques for lung cancer.
AB  - Cancer is one of most fatal forms of disease with rapid, abnormal and
      uncontrolled division of cells which spreads into different organs in the body.
      The primary aim of this review is to showcase the current and emerging diagnostic
      techniques that are used in lung cancer detection. Lung cancer is a leading cause
      of death among smokers and it has been emerging in non-smokers due to passive
      smoke inhalation by non-smokers. The mortality rate of patients with lung cancer
      is very high due to the change in lifestyle and environmental factors. It is
      often misdiagnosed as tuberculosis in India as tuberculosis is prevalent in
      India. On the contrary tuberculosis is not prevalent in the western countries
      Like U.S.A., U.K., Canada, etc. The major setback in lung cancer is that the
      symptoms of lung cancer occur at very later stages when the tumor has spread
      profusely. Hence, highly advanced techniques are employed for detection, accurate
      staging and treatment of lung cancer. The review focuses on the various novel and
      emerging diagnostic tools like biomarkers and biosensors, radiogenomics and
      artificial intelligence. This review also gives an insight of the various
      conventional techniques like CT-imaging, sputum cytology, biopsy and bronchoscopy
      which have been modified over the years for better sensitivity and accuracy. It
      also encompasses the regulatory provisions like IDE, CLIA-certification, etc. for
      manufacturing and sale of diagnostics in India, U.S.A., Japan and Australia.

PMID- 30119235
TI  - Long noncoding RNA VPS9D1-AS1 overexpression predicts a poor prognosis in non
      small cell lung cancer.
AB  - Long noncoding RNAs (LncRNAs) have been reported to play vital roles in non-small
      cell lung cancer (NSCLC). Recently, LncRNA/VPS9D1-AS1 has been reported to be
      overexpressed in various cancers. In this study, we aimed to investigate its
      expression pattern and clinical significance and further evaluate its prognostic
      value for NSCLC. VPS9D1-AS1 expression was examined in 184 NSCLC patients using a
      highly sensitive in situ hybridization protocol (RNAscope), and the expression
      values were correlated with the clinicopathological features. Another cohort
      including 12 NSCLC patients was used to validate the differential expression of
      VPS9D1-AS1 by qRT-PCR. TCGA datasets were further used to validate the main
      findings. We found that the levels of VPS9D1-AS1 were significantly higher in
      cancer tissues than in paired normal tissues from both lung squamous cell
      carcinoma (SCC) and adenocarcinoma (ADC) (P < 0.001). Importantly, the levels of
      VPS9D1-AS1 in patients with lung SCC were significantly higher than those in
      patients with lung ADC. The high levels of VPS9D1-AS1 were found to be associated
      with cancer lymph node metastasis (P = 0.020). Prognostic analysis revealed that
      the survival time for SCC patients with high levels of VPS9D1-AS1 was
      significantly shorter than that of patients with low levels of VPS9D1-AS1 (P =
      0.007). Therefore, our findings suggest that the overexpression of VPS9D1-AS1
      serves as a promising biomarker to predict the prognosis of NSCLC.

PMID- 30119236
TI  - Overexpression of MEG3 sensitizes colorectal cancer cells to oxaliplatin through
      regulation of miR-141/PDCD4 axis.
AB  - The existence of drug resistance is the main reason for chemotherapeutic failure
      in malignancies. Long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3)
      is implicated with tumorigenesis and chemoresistance. In the present study, we
      aimed to identify the role of MEG3 in oxaliplatin-resistant colorectal cancer
      (CRC) and its potential mechanisms. MEG3 was down-regulated in oxaliplatin
      resistant CRC tissues and cell lines. Low MEG3 expression was correlated with
      poor prognosis of CRC patients. Overexpression of MEG3 improved oxaliplatin
      sensitivity of HT29/OXA and HCT116/OXA cells. MEG3 suppressed miR-141 expression
      in HCT116/OXA cells. Moreover, MEG3 elevated PDCD4 expression through targeting
      miR-141, acting as a competing endogenous RNA (ceRNA). miR-141 inhibition or
      PDCD4 up-regulation could mimic the functional role in oxaliplatin resistance,
      which was counteracted by overexpression of MEG3. Collectively, MEG3 facilitated
      the sensitivity of CRC cells to oxaliplatin by regulating miR-141/PDCD4 axis,
      providing a novel therapeutic strategy for CRC.

PMID- 30119237
TI  - Modulatory effect of eugenol on arginase, nucleotidase, and adenosine deaminase
      activities of platelets in a carrageenan-induced arthritis rat model: A possible
      anti-arthritic mechanism of eugenol.
AB  - This study investigated the effect of eugenol on arginase, nucleotidase and
      adenosine deaminase activities in platelets of carrageenan-induced arthritic rat
      model to explain a possible anti-arthritic mechanism of eugenol. Fifty adult
      female rats (140-250 g) were divided into ten (10) groups (n = 5). Group I
      received oral administration of corn oil, group II received 2.50 mg/kg of
      eugenol, group III and IV rats received oral administration of 5.0 and 10.0 mg/kg
      of eugenol respectively, group V received 0.20 mg/kg of dexamethasone orally,
      group VI rats was injected with 1% carrageenan (arthritic rats) and received
      saline solution orally (arthritic control rat group), group VII, VIII and IX:
      arthritic rats received 2.50, 5.0 or 10 mg/kg of eugenol orally respectively,
      group X: arthritic rats was administered with 0.20 mg/kg of dexamethasone orally.
      The animals were treated for 21 days, thereafter, tibiofemoral histological
      examination, thiobabituric acid reactive substances level, arginase, nucleoside
      triphosphate diphosphohydrolase, 5'-nucleotidase and adenosine deaminase
      activities were assessed. Tibiofemoral histological examination result showed
      that infiltration of inflammatory cells was significantly decreased with an
      increase in eugenol dose. Activities of arginase, adenosine triphosphate and
      adenosine monophosphate hydrolyses were significantly decreased while adenosine
      diphosphate hydrolysis and adenosine deaminase activities were significantly
      increased in arthritic rat groups administered with different doses of eugenol.
      Therefore, eugenol might be a natural complement and alternative promising anti
      arthritic agent. These possible anti-arthritic mechanisms may be partly through
      the modulation of arginase and adenosine nucleotides hydrolyzing enzyme
      activities as well as the antioxidative action of eugenol.

PMID- 30119238
TI  - Insights of Leishmania (Viannia) braziliensis infection in golden hamster
      (Mesocricetus auratus) intestine.
AB  - AIM: The present study compared and evaluated morphological and quantitative
      alterations in the ileum of hamsters infected by two L. (V.) braziliensis strains
      isolated from patients with different lesion aspects and treatment responses.
      MAIN METHODS: Hamsters were infected in the left hindpaw with a suspension of
      promastigotes (2 * 107/100 MUl) of two different strains of L. (V.) braziliensis.
      After 90 or 120 days, the animals were euthanized. Samples of the ileum and
      mesenteric lymph node were collected for histological examination and
      quantitative polymerase chain reaction. KEY FINDINGS: All infected animals
      developed similar profile of paw lesions. In peripheral blood there was an
      increase in the number of mononuclear cells which contributed to elevated global
      leukocytes count. Increases in the width and height of villi and width and depth
      of crypts were observed. The thickness of the muscular layers, submucosa, and
      intestinal wall also increased. Histopathological alterations were observed,
      including inflammatory infiltrate in crypts and a large number of immune cells in
      the lamina propria, submucosa, and muscular layer. Immune cells were found inside
      myenteric ganglia, with an increase in the number of intraepithelial lymphocytes.
      Leishmania DNA was detected in the ileum and mesenteric lymph node at both times
      of infection. The presence of amastigotes in the ileum was revealed by
      immunohistochemistry. SIGNIFICANCE: The infection with different strains of L.
      (V.) braziliensis causes morphological and quantitative alterations in the ileum
      of hamsters and the parasite can migrate to the mesenteric lymph node and
      intestine.

PMID- 30119239
TI  - Ovarian extracellular MicroRNAs as the potential non-invasive biomarkers: An
      update.
AB  - Through the reproductive system, it has been realized that the microRNAs (miRNAs)
      have emerged as one of the principal post-transcriptional gene regulators of the
      diverse developmental processes. The ovary, as a dynamic organ, co-ordinates
      follicle recruitment, selection, and ovulation, in which miRNAs play the central
      role almost in its all functions. Deregulation of these developmental procedures
      in ovary could lead to the ovarian dysfunction, infertility, decrease in the
      assisted reproductive treatment (ART) outcome, and death in some patients with
      ovarian cancer. In recent years, detection of ovarian extracellular miRNAs in
      body fluids such as follicular fluid and serum/plasma has opened a new era in the
      biomarker discovery field. Here through the present review, different aspects of
      the potential and proposed involvement of the extracellular miRNAs in both
      physiologic and pathologic contexts of the ovary have been discussed. Moreover,
      the researchers have addressed the relevant findings, challenges, and issues
      which associated with the extracellular miRNAs in the ovarian microenvironments
      to provide the better insight into understanding the molecular mechanisms which
      were involved in the pathophysiologic conditions. Finally, a comprehensive survey
      of the gaps has been discussed to hopefully shed new light and perspective on the
      development of the novel diagnostic and therapeutic platforms in the clinic.

PMID- 30119240
TI  - Luteolin alleviates LPS-induced bronchopneumonia injury in vitro and in vivo by
      down-regulating microRNA-132 expression.
AB  - Bronchopneumonia is a common multiple infection disease under 2 years old.
      Luteolin is a natural flavonoid widely distributed in plants with anti
      inflammatory effect. This study aimed to explore the effects of luteolin on
      lipopolysaccharide (LPS)-induced bronchopneumonia injury in vitro and in vivo.
      Firstly, the viability and apoptosis of human bronchial epithelial BEAS-2B cells
      after luteolin treatment were assessed. Then, cells were treated with 10 MUM LPS
      to simulate inflammatory injury. The potential protective effects of luteolin on
      LPS-induced BEAS-2B cell inflammatory injury were detected. Moreover, after LPS
      and/or luteolin treatment, the expression of microRNA-132 (miR-132) in BEAS-2B
      cells was measured. The roles of miR-132 in protective activity of luteolin were
      investigated. Finally, the LPS-induced bronchopneumonia murine model was
      established and the anti-inflammatory effects of luteolin in vivo were analyzed.
      The results showed that LPS decreased BEAS-2B cell viability, increased cell
      apoptosis and enhanced inflammatory cytokines expression. Luteolin alleviated the
      LPS-induced viability loss, apoptosis and elevated expression of inflammatory
      cytokines in a dose-dependent manner. Moreover, luteolin alleviated the LPS
      induced miR-132 expression increase in BEAS-2B cells. Overexpression of miR-132
      reversed the protective effects of luteolin on LPS-induced inflammatory injury.
      Mechanistically, luteolin mitigated LPS-induced activation of NF-kappaB signaling
      pathway by down-regulation of miR-132. Furthermore, we also found that luteolin
      alleviated LPS-induced bronchopneumonia model in vivo. In conclusion, this study
      revealed that luteolin alleviated LPS-induced bronchopneumonia injury in vitro
      and in vivo through down-regulating miR-132. These findings provide theoretical
      basis for deeply exploring the treatment of bronchopneumonia in children by using
      luteolin.

PMID- 30119241
TI  - miR-516b functions as a tumor suppressor by directly modulating CCNG1 expression
      in esophageal squamous cell carcinoma.
AB  - BACKGROUND: miR-516b, as a tumor suppressor in several tumors, its regulatory
      role in esophageal squamous cell carcinoma (ESCC) hasn't been previously
      reported. OBJECTIVE: This study was to investigate the potential role of miR-516b
      in ESCC. METHODS: miR-516b expression was measured in ESCC tumor specimens and
      matched adjacent non-cancerous tissues from 80 ESCC patients. The association
      between miR-516b and clinicopathological features of these patients was analyzed.
      The effect of miR-516b was evaluated by cell proliferation, migration, invasion
      and apoptosis assays in ESCC cell line EC9706 and TE-9. The role of miR-516b in
      vivo was further studied by constructing ESCC xenograft mice model. The direct
      target of miR-516b was predicted by public miRNA database and confirmed by
      luciferase reporter assay. The regulation of miR-516b on the target gene was
      further confirmed in vitro and in vivo. The expressions of proteins related to
      cell cycle and apoptosis were analyzed by western blot analysis, and cell
      migration and invasion were assessed by transwell assays. RESULTS: miR-516b
      expression was reduced in ESCC tissues and cells, and correlated with advanced
      TNM stage, depth of invasion, lymphatic metastasis and poorer overall survival in
      ESCC patients. miR-516b was upregulated by miR-516b mimics repressing cell
      proliferation, and inducing G1 cell cycle arrest and apoptosis. miR-516b
      upregulation also suppressed the growth of ESCC xenograft tumor in nude mice and
      the invasion of ESCC cells via regulating the epithelial-mesenchymal transition
      pathway. CCNG1 was identified as a direct downstream target of miR-516b.
      CONCLUSION: The results demonstrated miR-516b functions as a tumor suppressor by
      directly modulating CCNG1 expression in ESCC cells, and may be a novel
      therapeutic and prognostic biomarker for ESCC.

PMID- 30119242
TI  - LncRNA SNHG16 reverses the effects of miR-15a/16 on LPS-induced inflammatory
      pathway.
AB  - Nowadays, neonatal sepsis has gradually become a global problem for its high
      incidence and increasing mortality. Previous studies have reported that miR-15a
      and miR-16 are two important modulators in neonatal sepsis. However, the upstream
      molecular mechanism of miR-15a/16 cluster is still mysterious. This study aims to
      explore a lncRNA can bind with miR-15a/16 in neonatal sepsis. Microarray analysis
      helped us found top ten lncRNAs which were downregulated in neonatal sepsis
      serum. Among these ten lncRNAs, SNHG16 was uncovered to significantly
      downregulated both miR-15a and miR-16. According to the result of subcellular
      fractionation assay, SNHG16 was mainly located in the cytoplasm of RAW264.7 cell,
      indicating the potential ceRNA role of SNHG16. Mechanism investigations revealed
      that SNHG16 could act as a ceRNA to upregulate TLR4 which is the target mRNA of
      miR-15a/16 cluster. At last, rescue assays demonstrated that SNHG16 reversed the
      effects of miR-15a/16 on LPS-induced inflammatory pathway. In summary, SNHG16 can
      act as a ceRNA to modulate miR-15a/16 cluster, thereby affecting LSP-induced
      inflammatory pathway which was downregulated by miR-15a/16 cluster.

PMID- 30119243
TI  - Crocin improves endometriosis by inhibiting cell proliferation and the release of
      inflammatory factors.
AB  - Endometriosis is one of the most common diseases in women. Inflammation and
      angiogenesis have been shown to be important in pathogenesis of endometriosis.
      Crocin is known as an anti-inflammatory, anti- proliferation substance. This
      study was designed to assess the potential effects of crocin on endometriosis. We
      established the mice model of endometriosis and administrated crocin to the mice.
      We monitored the endometriotic lesion growth, PCNA and VEGF expression in the
      lesion. We tested the serum levels of inflammatory cytokines in crocin-treated
      endometriosis mice. Finally we tested the effect of crocin on endothelial cell
      apoptosis and proliferation, and cytokine production in LPS-stimulated human
      monocyte. Crocin inhibited lesion growth in endometriosis mice and prevented PCNA
      and VEGF expression in the lesions. Crocin decreased the levels of inflammatory
      cytokines including INF-gamma, TNF-alpha, VEGF and IL-6 in serum. Crocin
      inhibited endothelial cells proliferation but did not cause apoptosis in
      endothelia cells. Crocin inhibited cytokine production in LPS-stimulated THP-1
      cells in vitro. Crocin protected endometriosis by inhibiting endothelial cells
      proliferation and preventing inflammatory cytokines production.

PMID- 30119244
TI  - 3-morpholinosydnonimine (SIN-1)-induced oxidative stress leads to necrosis in
      hypertrophic chondrocytes in vitro.
AB  - Chondrocyte is targeted for disruption in Osteoarthritis (OA) and Kashin-Beck
      Disease (KBD), and chondrocyte death in cartilage may contribute to the
      progression of OA and KBD. Oxidative stress leads to increased risk for OA.
      Previous work in our laboratory implicates oxidative stress as a potential
      mediator in children with KBD. While these studies suggest a role for oxidative
      stress in the modulation of OA and KBD, the direct effects of reactive oxygen
      species/reactive nitrogen species (ROS/RNS) on the stability of this domain
      remain unclear. Here, we demonstrate that oxidative stress, as induced through
      treatment with 3-morpholinosydnonimine (SIN-1), a spontaneous ROS/RNS generator,
      decreased the cell viability in hypertrophic chondrocytes in a dose- and time-
      dependent manner. SIN-1 induced necrosis in hypertrophic chondrocytes, whereas
      triggered apoptosis in non-hypertrophic cells of non-differentiated ATDC5 cells
      and C28/I2 cells. Ultrastructural analysis of hypertrophic chondrocyte treated
      with SIN-1 revealed morphological changes, such as plasma membrane breakdown,
      generalized swelling of the cytoplasm and organelles, even to disappearance.
      Moreover, SIN-1 induced chondronecrosis in the deep zone of engineered cartilage
      tissue, such as cell-free vacancy and "red ghost" cells. Overall, we demonstrate
      for the first time that oxidative stress, as induced through exogenous ROS/RNS,
      leads to necrosis in hypertrophic chondrocytes. Oxidative stress-mediated
      necrotic cell death contributes to chondronecrosis in the deep zone of cartilage
      in both OA and KBD.

PMID- 30119245
TI  - A comparison of the effects of thymoquinone, silymarin and N-acetylcysteine in an
      experimental hepatotoxicity.
AB  - This study investigated the effects of thymoquinone, silymarin, and N
      acetylcysteine in a rat model with carbon tetrachloride (CCl4)-induced
      hepatotoxicity. Although numerous similar studies are available, we aimed to
      compare the efficacy of these agents by considering N-acetylcysteine as a
      reference compound. A total of 50 male Wistar albino rats were randomly
      designated as 5 groups: Group I, CCl4; group II, thymoquinone and CCl4; group
      III, silymarin and CCl4; group IV, N-acetylcysteine and CCl4; group V, control
      group. CCl4 was administered intraperitoneally at a dose of 1.5 mL/kg (a mixture
      of CCl4: olive oil, 1:2) twice a week. Thymoquinone was administered at a dose of
      10 mg/kg, silymarin was administered at a dose of 100 mg/kg, and N-acetylcysteine
      was administered at a dose of 100 mg/kg by daily intraperitoneal injection. At
      the end of four weeks, blood and liver tests were analyzed. The results were
      evaluated statistically via the one-way ANOVA test. A p-value <0.05 was
      considered statistically significant. Thymoquinone, silymarin, and N
      acetylcysteine improved the levels of alanine aminotransferase, tumor necrosis
      factor-alpha, platelet-derived growth factor-BB, and interleukin-6, which were
      increased by CCl4. Thymoquinone and silymarin showed the positive increase in
      liver glutathione levels. Thymoquinone, silymarin, and N-acetylcysteine improved
      blood total oxidant status. In the histological examinations of liver tissue,
      thymoquinone decreased necrosis, and inflammation. The most positive decrease in
      the alpha-smooth muscle actin-stained hepatic stellate cell count was only
      observed with thymoquinone. These findings suggest that thymoquinone, silymarin,
      and N-acetylcysteine have potential for the treatment of diseases causing liver
      injury. Among these agents, thymoquinone showed the best results on most of the
      parameters. Since TQ appears to be at least as effective as SM and NAC in our in
      vitro study, we propose that it is time for clinical studies with thymoquinone on
      hepatotoxicity.

PMID- 30119246
TI  - Activation of the bile acid receptor GPBAR1 (TGR5) ameliorates interleukin-1beta
      (IL-1beta)- induced chondrocytes senescence.
AB  - Osteoarthritis is the most common chronic condition of the joint disease.
      Chondrocyte is the sole cell type in joint tissues. Senescence of chondrocytes is
      known to contribute to the causation of osteoarthritis. Local inflammatory
      cytokines- caused chondrocytes senescence is proposed to be one of the molecular
      mechanisms of osteoarthritis. In this study, we show that the bile acid receptor
      GPBAR1 (TGR5), a G protein couples bile acid receptor, plays important roles in
      protecting chondrocytes from interleukin 1beta (IL-1beta)- caused senescence.
      TGR5 is fairly expressed in cultured chondrocytes. Its expression is reduced in
      isolated chondrocytes from osteoarthritis patients, and IL-1beta treatment
      suppresses TGR5 expression. Activation of TGR5 by its synthetic agonist, INT-777,
      dramatically reduces senescence associated beta galactosidase activity by IL
      1beta. Mechanistically, the action of INT-777 ameliorates IL-1beta- induced
      chondrocytes entry of G0/G1 arrest phase and exit of S and G2/M phases. INT-777
      inhibits IL-1beta- induced expression of p21, PAI-1, and K382 acetylation of p53
      as well as reduction of Sirt1. The knockdown of TRG5 abolished the protective
      role of INT-777 on these molecules. Collectively, our data indicates that
      activation of TGR5 is necessary for protection of IL-1beta- induced chondrocytes
      senescence.

PMID- 30119247
TI  - Oxidized low density lipoprotein induces endothelial-to-mesenchymal transition by
      stabilizing Snail in human aortic endothelial cells.
AB  - The endothelial-to-mesenchymal transition (EndMT) of endothelial cells
      contributes to the development of atherosclerosis. Oxidized low density
      lipoprotein (ox-LDL) is a highly risk factor for atherosclerosis. However,
      whether ox-LDL causes EndMT and the underlying mechanism are unclear. We report
      here that ox-LDL treatment is able to induce EndMT in human aortic endothelial
      cells (HAECs), and that the ox-LDL-induced EndMT is strictly dependent on the
      presence of its innate receptor, ox-LDL Receptor-1 (LOX-1). In addition, ox-LDL
      specifically upregulates EndMT transcriptional factor Snail, and knockdown of
      Snail completely attenuates ox-LDL-induced EndMT, indicating an essential role of
      Snail in mediating this effect. Mechanically, ox-LDL induces Snail stabilization
      by inhibiting its ubiquitination, which is in part attributed to inhibited GSK
      3beta activity. Hence, our findings suggest that inducing EndMT of aortic
      endothelial cells by ox-LDL might contribute to its detrimental role in promoting
      atherosclerosis development.

PMID- 30119248
TI  - Inhibition of EP300 and DDR1 synergistically alleviates pulmonary fibrosis in
      vitro and in vivo.
AB  - OBJECTIVES: Pulmonary fibrosis is strongly correlated with inflammation factors,
      cytokine, and collagen secretion, whereby discoidin domain receptor 1 (DDR1)
      signaling plays an important role. EP300 is defined as an acetyltransferase that
      can acetylate histone and has been broadly studied in several chronic diseases,
      including cancer, inflammation and fibrosis. This study aimed to investigate the
      relationship between p300 and DDR1 in the pathological processes of pulmonary
      fibrosis. MATERIALS AND METHODS: Transcriptome analysis of single cell RNA
      sequencing for idiopathic pulmonary fibrosis (IPF) bronchial epithelial cells
      demonstrated that both DDR1 and EP300 were up-regulated and involved in the
      regulation of autophagy, cellular response to organonitrogen compounds, and
      collagen metabolic pathways, respectively. The anti-fibrotic and anti
      inflammation effects of Pim1 and DDR1 inhibitors in bleomycin-induced IPF murine
      models were estimated. RESULTS: We discovered that overexpression of EP300
      signaling induced MRC5 human fibroblast cells that up-regulated the expression of
      DDR1 and FN1; however, no effects on COL1 A1 and DDR1 phosphorylation were
      observed. Mechanistically, TGF-beta1 activated FN1, collagen, and DDR1 signaling
      could be reversed by the combination of p300 siRNA and DDR1 inhibitors. Moreover,
      the EP300 inhibitor SGC-CBP30 displayed synergistic effects with DDR1 inhibitors
      in pathogenic scores, airway goblet cell counts in bronchoalveolar lavage fluid
      (BALF), IL-4, IFN-gamma, FN1COL1 A1 secretion and alpha-SMA, a marker of
      myofibroblast. CONCLUSIONS: The EP300 siRNA and inhibitors sensitized DDR1
      inhibitors in our pulmonary fibrosis models in vitro and in vivo, implicating a
      combined inhibition of DDR1 with EP300 as potential therapies for IPF.

PMID- 30119249
TI  - The protective effects of a novel synthetic beta-elemene derivative on human
      umbilical vein endothelial cells against oxidative stress-induced injury:
      Involvement of antioxidation and PI3k/Akt/eNOS/NO signaling pathways.
AB  - Antioxidant therapy is considered as promising strategy for treating oxidative
      stress-induced cardiovascular disease. Bis (beta-elemene-13-yl) glutarate (BEG)
      is a novel beta-elemene derivative. Herein, we examined the antioxidant activity
      of BEG on human umbilical vein endothelial cells (HUVECs) after injury with
      hydrogen peroxide (H2O2) and investigated the mechanism involved. HUVECs were
      divided into the following groups: control group (untreated cells); treated
      groups (cells treated with 0.1, 1, 10 MUmol/L of BEG); positive control group
      (cells treated with 0.1 mM Vitamin E); model group (cells treated with 0.5 mM
      H2O2 alone). Cells were pre-incubated with or without BEG for 24 h and then
      incubated for a further 2 h with 0.5 mM H2O2. Our results showed that BEG
      significantly reduced H2O2 induced loss in endothelial cell viability, reactive
      oxygen species (ROS) production, reduced lactate dehydrogenase (LDH) release, and
      malonyldialdehyde (MDA) level in a concentration-dependent manner. Also, BEG
      increased the cellular the superoxide dismutase (SOD) activity. Moreover, we
      found that H2O2 decreased Akt and eNOS phosphorylation, which perhaps, indirectly
      reduced nitric oxide (NO) production. These effects induced by H2O2, however,
      were reduced by pre-treatment with BEG. BEG effects were inhibited by a PI3K
      inhibitor (wortmannin) and eNOS inhibitor (L-NAME). In conclusion, the present
      study demonstrated that BEG has antioxidant activity. Furthermore, BEG reduced
      H2O2-induced endothelial cells injury by the involvement of antioxidation and
      PI3K/Akt/eNOS/NO signaling pathways.

PMID- 30119250
TI  - miR-208b targets Bax to protect H9c2 cells against hypoxia-induced apoptosis.
AB  - BACKGROUND: miR-208 family members have been considered as promising biomarkers
      in myocardial infarction (MI). Among which, miR-208a and miR-499 are reported to
      function as ischemic injury promoting miRNAs. This study aimed to explore the in
      vitro function of miR-208b in MI, which has not been widely studied. METHODS: RT
      qPCR was conducted to measure the expression changes of miR-208b in MI patients,
      MI mouse model and H9c2 cells stimulated by hypoxia. H9c2 cells were subjected to
      hypoxia before which miR-208b expression was altered by transfection. CCK-8, flow
      cytometry and Western blot were performed to detect cell survival. Besides, the
      regulatory relationship between miR-208b, Bax, and PI3K/AKT was tested by
      luciferase reporter, RT-qPCR and Western blot. RESULTS: Serum levels of miR-208b
      in MI patients were significantly higher than those in the healthy controls.
      Also, miR-208b was up-regulated in mouse model and cell model of MI.
      Overexpression of miR-208b protected H9c2 cells against hypoxia-induced
      apoptosis, as the viability was increased, apoptosis rate was decreased, Bax and
      Cytochrome c were down-regulated, and Bcl-2 was up-regulated. Bax was a target
      gene of miR-208b. And miR-208b could not protect H9c2 cells when Bax was
      overexpressed. More interestingly, miR-208b activated PI3K/AKT pathway via
      targeting Bax, and the activated PI3K/AKT pathway could further repress Bax
      expression. Finally, blocking PI3K/AKT pathway by using LY294002 eliminated the
      myocardioprotective effects of miR-208b. CONCLUSION: miR-208b is highly expressed
      during MI, and miR-208b protects H9c2 cells against hypoxia-induced apoptosis.
      miR-208b exerts myocardioprotective effect via targeting Bax and activating
      PI3K/AKT pathway.

PMID- 30119251
TI  - Involvement of organic cation transporter 2 in the metformin-associated increased
      lactate levels caused by contrast-induced nephropathy.
AB  - The application of iodinated contrast medium has become a risk factor for
      metformin-associated lactic acidosis (MALA), which leads to the accumulation of
      metformin in vivo is one of the principal reasons for MALA. However, the
      molecular mechanism of the adverse event is not yet clear. In this study, iohexol
      injection was used as a model drug. The contrast agent acute kidney injury rat
      model, in vivo rat pharmacokinetic study, kidney slices and HK-2 cells were
      performed to elucidate the pharmacokinetic molecular mechanism of accumulation of
      metformin caused by contrast-induced nephropathy (CIN). Plasma exposure of
      metformin was increased significantly in the CIN group compared with that in the
      normal and control groups. The AUC of metformin was from 2791 +/- 382 MUg min mL
      1 to 4784 +/- 767 MUg min mL-1. The cumulative urinary excretion of metformin was
      also reduced in the CIN group. The uptake of metformin decreased in kidney slices
      in the CIN group. Compared with the normal and control groups, the blood lactate
      concentration was increased after intravenous administration of metformin in the
      CIN group followed a similar trend to the plasma concentrations of metformin.
      After treatment with contrast medium, the expression of OCT2 was reduced in rat
      kidney and HK-2 cells. These findings highlight that OCT2 deficiency was
      associated with increased lactate levels during metformin treatment caused by
      CIN.

PMID- 30119252
TI  - Reduction of cisplatin-induced renal and hepatic side effects in rat through
      antioxidative and anti-inflammatory properties of Malva sylvestris L. extract.
AB  - BACKGROUND: Cisplatin is widely used in the chemotherapy of solid organ cancers.
      However, its application is associated with serious side effects in various
      organs including the kidneys and liver. OBJECTIVES: The aim of this study was to
      investigate the effects of mallow extract on the side effects of cisplatin in the
      kidneys and liver. METHODS: Hydroalcoholic extract of mallow, at doses of 200,
      400, and 600 mg/kg BW, was administered to the animals for seven days
      intraperitoneally (ip). Animals in the Cis + Mallow group received a dose of
      cisplatin (8 mg/kg, ip) on the third day. Renal and hepatic functional
      disturbances were evaluated by measuring concentrations of creatinine, urea
      nitrogen, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in
      the plasma. In order to assess oxidative stress, malondialdehyde (MDA) and ferric
      reducing antioxidant power (FRAP) levels were measured in the kidney tissue.
      Then, degree of mRNA expressions of TNF-alpha and ICAM-1 were measured to examine
      renal inflammation. Hematoxylin and Eosin (H & E) staining of kidney and liver
      tissues was performed to study tissue damage and leukocyte infiltration. RESULTS:
      Cisplatin increased levels of plasma creatinine, urea-nitrogen, AST, and ALT;
      levels of tissue damage and leukocytes infiltration in the kidneys and liver; and
      MDA level and expression of pro-inflammatory factors in the kidney tissue.
      Meanwhile, it decreased FRAP level in the kidney tissue. Pretreatment by mallow
      extract resulted in significant improvement in all measured variables although
      200-mg and 400-mg doses yielded better results. CONCLUSION: Results showed that
      mallow supplement protects the kidneys and liver against side effects of
      cisplatin, and reduces the resultant oxidative stress and inflammation.

PMID- 30119253
TI  - Albizia zygia root extract exhibits antipsychotic-like properties in murine
      models of schizophrenia.
AB  - BACKGROUND: The root extract of Albizia zygia (DC.) J.F. Macbr. (Leguminosae) is
      used to manage mental disorders in African traditional medicine. However, its
      value, particularly, against negative and cognitive symptoms of schizophrenia
      have not been evaluated. AIM: The aim of this study was to evaluate the
      antipsychotic properties of the hydroethanolic root extract of Albizia zygia
      (AZE) against positive, negative and cognitive symptoms of schizophrenia in
      animal models. MATERIALS AND METHODS: The effects of AZE (30-300 mg kg-1) were
      evaluated against apomorphine-induced cage climbing as well as ketamine -induced
      hyperlocomotion, -enhanced immobility, -impaired social interaction and novel
      object recognition. The propensity of AZE to induce catalepsy and to attenuate
      haloperidol-induced catalepsy were also investigated. RESULTS: AZE 30-300 mg kg-1
      significantly reduced apomorphine-induced climbing behaviour as well as ketamine
      induced hyperlocomotion, immobility and object recognition deficits (at least P <
      0.05). Moreover, the extract showed no cataleptic effect but significantly
      inhibited haloperidol-induced catalepsy at a dose of 30 mg kg-1 (P < 0.05).
      CONCLUSION: The root extract of Albizia zygia exhibited an antipsychotic-like
      activity in mice with potential to alleviate positive, negative and cognitive
      symptoms of schizophrenia.

PMID- 30119254
TI  - Inhibition of SETD7 protects cardiomyocytes against hypoxia/reoxygenation-induced
      injury through regulating Keap1/Nrf2 signaling.
AB  - The protein SET domain-containing lysine methyltransferase 7 (SETD7) has recently
      been shown to regulate apoptosis in various cells. However, the role of SETD7 on
      cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury remains
      unclear. This study aimed to investigate the potential role of SETD7 in
      hypoxia/reoxygenation (H/R)-induced apoptosis of rat cardiomyocytes and reveal
      the underlying mechanism. Our results demonstrated that SETD7 expression was
      significantly up-regulated in cardiomyocytes in response to H/R injury. The
      inhibition of SETD7 by siRNA-mediated gene silencing significantly suppressed H/R
      induced apoptosis and decreased the production of reactive oxygen species (ROS).
      The overexpression of SETD7 markedly enhanced H/R-induced apoptosis and ROS
      production. Moreover, the knockdown of SETD7 reduced the expression of Keap1 and
      promoted the expression of Nrf2. In addition, the knockdown of SETD7 increased
      the activity of antioxidant response element and promoted the expression of heme
      oxygenase-1 and NADPH-quinone oxidoreductase 1. However, the knockdown of Nrf2
      partially abrogated the SETD7 inhibition-mediated protective effect against H/R
      injury. Taken together, these results indicate that the inhibition of SETD7
      attenuates H/R-induced injury of cardiomyocytes via the down-regulation of Keap1
      and promotion of the Nrf2-mediated anti-oxidation signaling pathway.

PMID- 30119255
TI  - Long noncoding RNA SNHG12 mediates doxorubicin resistance of osteosarcoma via miR
      320a/MCL1 axis.
AB  - The long non-coding RNA small nucleolar RNA host gene 12 (SNHG12) overexpression
      was found in various tumors and the dysregulated expression of SNHG12 contributed
      to multidrug resistance in non-small cell lung cancer. However, the role of
      SNHG12 in doxorubicin resistance of osteosarcoma is still unclear. In present
      study, we explored the function and underlying mechanism of SNHG12 on doxorubicin
      resistance in osteosarcoma. High expression of SNHG12 was associated with
      doxorubicin resistance and a poor overall survival in osteosarcoma. Furthermore,
      doxorubicin-resistant cells revealed a higher expression of SNHG12 compared with
      doxorubicin-sensitive cells. Moreover, dual luciferase reporter and RNA
      immunoprecipitation assays revealed that miR-320a targeted to SNHG12. Besides,
      knockdown of SNHG12 contributed to the upregulation of miR-320a and improved the
      sensitivity of doxorubicin. Additionally, miR-320a inhibited the expression of
      Myeloid cell leukemia 1 (MCL1). Finally, the results indicated that SNHG12
      mediated doxorubicin resistance of osteosarcoma via miR-320a/MCL1 axis.

PMID- 30119256
TI  - Synergy of theophylline reduces necrotic effect of berberine, induces cell cycle
      arrest and PARP, HMGB1, Bcl-2 family mediated apoptosis in MDA-MB-231 breast
      cancer cells.
AB  - Berberine, is a plant alkaloid, proved to have anticancer effect on various
      cancers. Theophylline (TH), a natural product, is widely used in the treatment of
      respiratory difficulties. The present study designed to elucidate the effects of
      theophylline and berberine combination on breast cancer cells cytotoxicity, gene
      expression and cell cycle. MTT assay revealed that berberine inhibited MDA-MB-231
      breast cancer cells viability in a time and dose dependent manner (IC50 of 100
      MUM) but theophylline had no considerably effect on the cells. Combined treatment
      of berberine and theophylline showed a synergistic anti-proliferation effect,
      IC50 of berberine reduced to 50 MUM and the cells were arrested at G2/M phase.
      Combined treatment of Berberine and theophylline reduced extracellular level of
      HMGB1 and down regulated HMGB1 and MMP-9 mRNA expression. The results of flow
      cytometry using annexin/PI staining of the cells, HMGB1 release, and poly ADP
      ribose polymerase cleavage demonstrated that theophylline attenuated necrotic
      effect of berberine and increased the level of apoptotic cell death. Enhancement
      of Bax content detected by ELISA and upregulation of Bax mRNA expression, down
      regulation of Bcl-2 expression and increase of anion superoxide production
      confirmed induction of apoptosis via intrinsic apoptotic pathway. Replacement of
      theophylline with exogenous cyclic AMP in combination treatment represented
      similar effect on berberine cytotoxicity. From the results it is concluded that
      synergistic anticancer effect of theophylline and berberine suggests that
      combination of these two drugs may be an effective therapeutic agent against
      breast cancer cell.

PMID- 30119258
TI  - Inhibition of IL-18 reduces renal fibrosis after ischemia-reperfusion.
AB  - Acute kidney injury induced by ischemia-reperfusion injury (IRI) is a high risk
      factor in the progression towards chronic kidney disease, which is featured by
      renal interstitial fibrosis. Interleukin (IL)-18 is produced by T cells and
      macrophages and has been involved in the pathophysiology of IRI. However, the
      role of IL-18 in IRI-induced renal fibrosis is poorly understood. In the present
      study, we showed that interleukin (IL)-18 was significantly up-regulated after
      IRI stress. Mice treated with IL-18 Bp, a natural inhibitor of IL-18, presented
      less severe fibrotic response in the kidneys following IRI compared with vehicle
      treated mice. Inhibition of IL-18 decreased myofibroblasts formation in the
      kidneys in response to IRI, which was associated with reduction of fibronectin
      and collagenIproteins. Moreover, inhibition of IL-18 impaired infiltration of
      CD3+ T cells and F4/80+ macrophages in the kidneys of mice after IRI. Treatment
      with IL-18 Bp reduces the levels of profibrotic molecules in the kidneys of mice
      following IRI. Finally, administration of IL-18 Bp impedes the transition of M2
      macrophages to myofibroblasts and suppressed the accumulation of bone marrow
      derived M2 macrophages. Adoptive transfer of M2 macrophages abolished the anti
      fibrotic effect of IL-18 Bp. In summary, our results suggest that IL-18 plays an
      important role in the progression of IRI-induced renal fibrosis via modulating
      inflammation cells infiltration, the expression of inflammatory cytokines and
      chemokines, and the transition of bone marrow-derived M2 macrophages to
      myofibroblasts.

PMID- 30119257
TI  - Curcumin reduces Ly6Chi monocyte infiltration to protect against liver fibrosis
      by inhibiting Kupffer cells activation to reduce chemokines secretion.
AB  - Curcumin has been reported to have anti-fibrotic effect. However, the anti
      fibrotic mechanism of curcumin for liver fibrosis remains obscure. In the
      presenting study, we aimed to investigate whether curcumin reduce chemokines
      secretion by inhibiting kupffer cells (KCs) activation to decrease Ly6Chi
      monocyte infiltration in the treatment of liver fibrosis. Liver fibrosis was
      induced by intraperitoneal carbon tetrachloride (CCl4)-injection in mice. Mice in
      curcumin group received curcumin treatment by gavage. Pretreatment with curcumin
      significantly protected mice from liver inflammation and fibrosis. Compared to
      CCl4 group, mice in the curcumin group showed significantly less intrahepatic
      infiltration of Ly6Chi monocytes, but no difference of other leucocyte subtypes.
      Moreover, curcumin significantly reduced Ly6Chi monocytes associated pro
      inflammatory and pro-fibrogenic cytokines, which was in line with the decreased
      numbers of intrahepatic Ly6Chi monocytes. Further study found that curcumin is
      able to decrease KCs activation and monocyte chemokines, which explains why
      curcumin can reduce Ly6Chi monocytes infiltration during liver fibrosis. In
      vitro, we discovered that curcumin prevents the polarization of macrophages
      toward M1 and reduces monocyte chemokines secretion, which is involved with
      ERK1/2 and p38 pathways. Taken together, for the first time, we verified that
      curcumin can reduce chemokines secretion by inhibiting KCs activation to decrease
      Ly6Chi monocyte infiltration in the treatment of liver fibrosis. These results
      suggested that curcumin may be considered a promising candidate in the prevention
      and treatment of liver fibrosis.

PMID- 30119259
TI  - Long noncoding RNA HOXD-AS1 aggravates osteosarcoma carcinogenesis through
      epigenetically inhibiting p57 via EZH2.
AB  - Osteosarcoma is the most common primary malignant bone tumor and long non-coding
      RNAs (lncRNAs) have been proved to epigenetically regulate the oncogenesis of
      osteosarcoma. In this research, we investigate the role of lncRNA HOXD-AS1 on the
      osteosarcoma oncogenesis. Results revealed that HOXD-AS1 expression level was
      significantly up-regulated in osteosarcoma tissue and cells, moreover, the
      aberrant overexpression predicted the poor prognosis of osteosarcoma patients.
      Loss-of-functional experiments indicated that HOXD-AS1 silencing inhibited the
      osteosarcoma cells proliferation and induced G1/G0 phase arrest in vitro, and
      repressed tumor cell growth in vivo. Mechanistic investigations showed that HOXD
      AS1 epigenetically repressed p57 through recruiting enhancer of zeste homolog 2
      (EZH2) to the promoter of p57. Rescue experiments revealed that p57 could recover
      the oncogenic role of HOXD-AS1 on osteosarcoma. In conclusion, our study
      confirmed that HOXD-AS1 could interact with EZH2, and then repress p57
      expression, to aggravate osteosarcoma oncogenesis. which provide new idea for the
      osteosarcoma tumorigenesis.

PMID- 30119260
TI  - Hepatoprotective effect of alpha-mangostin against lipopolysaccharide/d
      galactosamine-induced acute liver failure in mice.
AB  - The purpose of this study was to investigate the hepatoprotective effect of alpha
      mangostin (alpha-MG) on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced
      acute liver failure and discover its potential mechanisms in mice. The results
      showed that alpha-MG could attenuate LPS/D-GalN-induced liver pathological
      injury, and decrease the hepatic malondialdehyde (MDA) level, serum alanine
      aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor (TNF
      alpha), interleukin-1beta and 6 (IL-1beta, IL-6) levels and recovery hepatic
      glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) activities. The
      results also indicated that alpha-MG inhibited LPS/D-GalN-induced toll-like
      receptor 4 (TLR4) expression and NF-kappaB activation. In addition, alpha-MG up
      regulated the expressions of Nrf2 and heme oxygenase-1 (HO-1). In conclusion, the
      results indicated that alpha-MG could protect against LPS/D-GalN-induced liver
      failure by activating Nrf2 to induce antioxidant defense and inhibiting TLR4
      signaling pathway to induce anti-inflammatory effect.

PMID- 30119261
TI  - Schisandrin A prevents oxidative stress-induced DNA damage and apoptosis by
      attenuating ROS generation in C2C12 cells.
AB  - The generation of excessive reactive oxygen species (ROS) by oxidative stress has
      various deleterious effects on cellular constituents. Therefore, the discovery of
      natural products that can inhibit the production of ROS may be effective in
      suppressing the onset and treatment of oxidative stress-mediated diseases.
      Despite the antioxidant efficacy studies on various substances in the genus
      Schisandra used as traditional medicine, research on the efficacy of schisandrin
      A, a class of active lignans, remains insufficient. This study was conducted to
      evaluate the protective effect of schisandrin A on DNA damage and apoptosis
      induced by hydrogen peroxide (H2O2) in C2C12 cells. Results showed that
      schisandrin A effectively attenuated H2O2-induced cytotoxicity and DNA damage,
      which was related to the blockage of ROS accumulation. Schisandrin A also
      prevented the decrease in ATP content by H2O2 and restored the H2O2-induced
      activation of AMP-activated protein kinase. In addition, schisandrin A prevented
      the release of H2O2-induced cytochrome c into the cytoplasm presumably by
      inhibiting the loss of mitochondrial membrane potential and the changes in the
      Bcl-2 family protein expression by H2O2. Furthermore, the blocking of H2O2
      induced apoptosis by schisandrin A was associated with the inhibition of poly
      (ADP-ribose) polymerase degradation by the inactivation of caspase-3. These
      results suggest that schisandrin A maintains energy metabolism through the
      preservation of mitochondrial function while eliminating ROS generated by H2O2 in
      C2C12 cells. Therefore, our data indicate that schisandrin A may have a
      beneficial effect on the prevention and treatment of diseases associated with
      apoptosis induced by oxidative stress.

PMID- 30119262
TI  - Assessment of dose-response relationship of 5-fluorouracil to murine intestinal
      injury.
AB  - 5-Fluorouracil (5-FU) is the most frequently prescribed anti-tumor drug, but has
      been reported to result in intestinal injury. Although some progress has been
      made in understanding the intestinal toxicity of 5-FU, confusion remains about
      animal models of 5-FU-induced intestinal injury, especially the dosage of 5-FU.
      This study aims to assess the dose-response relationship between the severity of
      intestinal injury and different doses of 5-FU, and to determine a proper dosing
      for the murine model. We found that mice in the 5-FU groups gradually lost body
      weight over time. Increasing doses of 5-FU resulted in more severe diarrhea, with
      a concomitant increase in mortality. Histopathological damage was more severe in
      mice that received higher doses of 5-FU. In addition, plasma diamine oxidase
      (DAO) activity decreased in experimental mice with intestinal injury in a dose
      dependent way. TUNEL and western blot analysis showed cell apoptosis in the ileum
      and colon related to 5-FU dosage. However, administration of 200 and 400 mg/kg 5
      FU caused extremely high mortality, severe diarrhea and histopathological damage,
      but 25 mg/kg 5-FU did not result in significant intestinal injury. The severity
      of intestinal injury induced by 5-FU appeared to be dose-dependent and we
      concluded that the proper dosage of 5-FU to induce a murine model with intestinal
      mucositis ranged from 50 mg/kg to 100 mg/kg.

PMID- 30119263
TI  - Reversible effects of anabolic steroid abuse on cyto-architectures of the heart,
      kidneys and testis in adult male mice.
AB  - The importance of the present study comes from the lack of sufficient information
      about the reversibility of the histopathological alterations which may result
      from anabolic androgenic drugs abuse after some times of stop treatment, as it is
      one of the prior studies which explored the negative effects of Deca-Durabolin
      abuse in particular on the hearts, kidneys and testis structures. For this aim,
      study was performed on 40 male adult mices. Animals were divided into five groups
      of 8 animals each as follows: treated by Deca-Durabolin (nandrolone decanoate) at
      30 g/kg of BW, weekly during one month (GI); two months (GII); three months
      (GIII); three months followed by six weeks of treatment discontinuation (GIV) and
      Control (C). Cytohistological exam was performed to determine histopathological
      damage in heart, kidney and testis tissues. Results showed that the treated
      animals supported very well the administrated substance. The increase in muscle
      strength and the absence of aggression were the most noticeable traits in longer
      term treated groups. In addition, the gains in body and heart weights increase
      with duration of treatment and even more after stopping treatment. Our study
      showed important degenerative changes and disorganization of the histological
      structure of heart, kidney and testis in the animals of GIII. These damages
      worsen again 6 weeks after stopping treatment in heart and kidney, and repairs
      incompletely in the testis. In conclusion, these results confirmed that the use
      of AAS is associated with a lot of deleterious effects on the cardiac, nephritic
      and gonadic tissues which cannot be reversible.

PMID- 30119264
TI  - Suppression of microRNA-495 alleviates high-glucose-induced retinal ganglion cell
      apoptosis by regulating Notch/PTEN/Akt signaling.
AB  - High glucose (HG)-induced apoptosis of retinal ganglion cells (RGCs) contributes
      to the pathogenesis of diabetic retinopathy, which is one of the most common and
      severe complications of diabetes mellitus. Accumulating evidence has documented
      that microRNAs (miRNAs) play an important role in the pathogenesis of diabetic
      retinopathy. However, the role of miRNAs in regulating HG-induced apoptosis of
      RGCs remains largely unknown. Various studies have suggested that miR-495 is an
      important regulator of cell apoptosis and survival. In this study, we aimed to
      investigate whether miR-495 is involved in regulating HG-induced apoptosis of
      RGCs and reveal its possible relevance in diabetic retinopathy. We found that miR
      495 was significantly upregulated in HG-treated RGCs. Downregulation of miR-495
      protected RGCs against HG-induced apoptosis, whereas overexpression of miR-495
      had the opposite effect. Notably, Notch1 was identified as a target gene of miR
      495, as miR-495 negatively regulated Notch1 expression and the Notch signaling
      pathway. Moreover, downregulation of miR-495 inhibited PTEN expression while
      promoting Akt activation. However, knockdown of Notch1 significantly abolished
      the protective effect of miR-495 inhibition against HG-induced apoptosis.
      Overall, our study suggests that downregulation of miR-495 alleviates HG-induced
      apoptosis of RGCs by targeting Notch1 to regulate PTEN/Akt signaling, which
      provides novel insights into understanding the pathogenesis of HG-induced
      apoptosis of RGCs.

PMID- 30119265
TI  - Time-shifted co-administration of sub-analgesic doses of ambroxol and pregabalin
      attenuates oxaliplatin-induced cold allodynia in mice.
AB  - BACKGROUND: Oxaliplatin-induced cold allodynia is a frequent complication
      appearing in patients treated with this anti-tumor drug. Since, there are no
      clear algorithms to overcome this painful condition effectively, it is important
      to establish novel strategies for its treatment. AIM: In this study, the ability
      of pregabalin and ambroxol, used as single drugs or in combinations administered
      in a time-shifted manner to attenuate cold allodynia was assessed in the mouse
      cold plate test. The hot plate test was additionally used to assess
      antinociceptive properties of ambroxol in the acute, thermally-induced pain
      model. Locomotor activity and motor coordination of mice were also evaluated. In
      silico studies were undertaken to predict potential binding of ambroxol to sodium
      channel (Nav) subtypes whose overexpression is implicated in the development of
      oxaliplatin-induced neuropathic pain. KEY FINDINGS: A hyperadditive antiallodynic
      effect of combined sub-analgesic ambroxol and pregabalin was demonstrated in
      oxaliplatin-treated mice. This effect was particularly strong when these drugs
      were given 4 h apart. Both drugs used in combination reduced animals' locomotor
      activity, but they did not impair motor coordination in the rotarod test.
      Ambroxol did not show antinociceptive properties in the hot plate test. The
      molecular docking studies predicted that in mice ambroxol might bind to Nav1.6
      and Nav1.9 rather than Nav1.7 and Nav1.8. SIGNIFICANCE: Time-shifted co
      administration of sub-analgesic doses of ambroxol and pregabalin effectively
      attenuates oxaliplatin-induced cold allodynia. Molecular docking model predicts
      preferential binding of ambroxol to mouse Nav1.6, Nav1.9 channels. This
      mechanism, if confirmed in vitro, might explain pharmacological activities
      observed in vivo.

PMID- 30119266
TI  - Betulin inhibits lipopolysaccharide/D-galactosamine-induced acute liver injury in
      mice through activating PPAR-gamma.
AB  - Betulin is a phenolic flavonoid which has been reported to possess a mass of
      pharmacological properties, especially anti-inflammatory activity. The purpose of
      this study was to explore the protective effects and possible mechanism of
      betulin against lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced acute
      liver injury. D-Gal and LPS were intraperitoneally injected to develop acute
      liver injury animal model. Betulin (2, 4 or 8 mg/kg) were given 1 h before LPS/D
      Gal instillation. Liver tissues and plasma samples were collected 9 h after LPS/D
      Gal were given. The results indicated that betulin dramatically decreased liver
      pathologic changes, myeloperoxidase (MPO) activity, serum alanine
      aminotransferase (ALT) and aspartate aminotransferase (AST) levels.
      Simultaneously, the levels of interleukin (IL-1beta) and tumor necrosis factor
      (TNF-alpha) in serum and liver tissues were both attenuated by betulin. Besides,
      betulin suppressed NF-kappaB pathway activation in a dose-dependently manner.
      Betulin increased the expression of PPAR-gamma in a dose-dependent manner. In
      conclusion, all these results revealed that betulin could possess potential
      therapeutic effect for LPS/D-Gal-induced acute liver injury.

PMID- 30119267
TI  - Cytotoxicity and apoptosis enhancement in breast and cervical cancer cells upon
      coadministration of mitomycin C and essential oils in nanoemulsion formulations.
AB  - The present study aimed to solubilize the antineoplastic agent, mitomycin C
      (MMC), in two nanoemulsions (NEs) consisting of different essential oils (ginger
      (Gi) and frankincense (Fr)) in order to examine their anticancer activities on
      the HeLa cervical cancer cells and MCF-7 breast cancer cells. The two NEs-based
      Gi and Fr oil were produced by a high-pressure homogenization technique followed
      by solubilizing of the MMC in both NE formulas. The produced formulas were
      physically characterized by zetasizer and were applied on HeLa and MCF-7 cells at
      various concentrations for 24 h. The cytotoxicity assays were performed in vitro,
      using MTT assay, Coomassie blue staining for cellular morphology evaluation, and
      DAPI fluorescent staining for molecular cell death assessment. The average
      droplet diameters of the blank NEs have markedly increased and the charges of the
      droplets were significantly reversed when MMC was loaded. The potential
      cytotoxicity of the blank and combined formulas on HeLa and MCF-7 cells were dose
      dependent and significantly greater than the toxicities of the free MMC. Among
      the MMC-loaded NE formulas, Fr-MMC has endured the nuclear apoptosis in HeLa
      cells at a lower concentration and reported the least % of florescence uptake
      compared to Gi-MMC. In contrast, the combination formula, Gi-MMC, has the
      strongest apoptotic effect on the MCF-7 cell line since it has the least %
      florescence uptake compared to the other formulations. Mixing MMC with Gi-NE and
      Fr-NE has considerably improved its cytotoxicity on the MCF-7 and HeLa cells.

PMID- 30119268
TI  - Potential role of leukotriene receptor antagonists in reducing cardiovascular and
      cerbrovascular risk: A systematic review of human clinical trials and in vivo
      animal studies.
AB  - BACKGROUND: Leukotrienes are important lipid mediators of inflammation arising
      from arachidonic acid cascade. They are implicated in vascular inflammation and
      produced in different pathologic conditions as atherosclerosis, stroke and
      myocardial infarction. Different studies have investigated the role of
      leukotriene receptor antagonist (LTRA) in reducing some cardiovascular events,
      especially in animals. We conducted a systematic review of both in vivo animal
      and human studies to determine the potential role of leukotriene receptor
      antagonist in reducing cardiovascular and cerebrovascular events. METHODS: Data
      sources: Pubmed, Embase and Cochrane database. DATA EXTRACTION: Two reviewers
      independently screened potentially eligible articles and extracted relevant data.
      RESULTS: A total of 28 studies were included, of which 26 were conducted in
      animals, and 2 in humans. CONCLUSIONS: All animal studies reported that using a
      leukotriene receptor antagonist brings to a reduction of either myocardial
      infarction, ischemic stroke, or atherosclerosis risk. Similar results were
      obtained from two clinical trials on humans, suggesting a potential role of
      montelukast in reducing some cardiovascular diseases.

PMID- 30119269
TI  - Liquiritigenin attenuates high glucose-induced mesangial matrix accumulation,
      oxidative stress, and inflammation by suppression of the NF-kappaB and NLRP3
      inflammasome pathways.
AB  - Oxidative stress, inflammation, and hyperglycemia are considered to play crucial
      roles in the pathogenesis and progression of diabetic nephropathy (DN).
      Liquiritigenin, one of the flavonoid compounds, has been shown to possess anti
      inflammatory, anti-hyperlipidemic, and anti-oxidative properties. Our study aimed
      to explore the effects of liquiritigenin on high glucose (HG)-induced
      extracellular matrix (ECM) accumulation, oxidative stress and inflammatory
      response and delineate the underlying mechanism. In our study, glomerular
      mesangial cells (HBZY-1) were co-treated with various doses of liquiritigenin and
      HG. We found that HG, but not normal glucose or mannitol, promoted the
      proliferation of HBZY-1 cells, which was suppressed by liquiritigenin.
      Liquiritigenin inhibited HG-induced ECM accumulation in HBZY-1 cells by reducing
      the expressions and production of collagen IV (Col IV) and fibronectin (FN).
      Moreover, liquiritigenin attenuated HG-induced oxidative stress, as evidenced by
      the decreased MDA content and NADPH oxidase 4 (NOX4) expression, and the
      increased SOD activity in HBZY-1 cells. Liquiritigenin suppressed HG-induced
      inflammatory response, as demonstrated by the reduced expressions and secretion
      of interleukin (IL)-6 and IL-1beta in HBZY-1 cells. Furthermore, we found that
      liquiritigenin inhibited HG-induced activation the nuclear factor-kappa B (NF
      kappaB) and nod-like receptor protein 3 (NLRP3) inflammasome pathways. In
      conclusion, these results demonstrated that liquiritigenin attenuated HG-induced
      ECM accumulation, oxidative stress, and inflammation by suppression of the NF
      kappaB and NLRP3 inflammasome pathways, suggesting that liquiritigenin might be a
      promising therapeutic agent for preventing the development of DN.

PMID- 30119270
TI  - miR-335-5p targeting ICAM-1 inhibits invasion and metastasis of thyroid cancer
      cells.
AB  - miRNAs is a kind of noncoding small RNAs with negative regulation function. Some
      miRNAs play a crucial role in the growth of tumor cells. In this study, we
      analyzed the role of miR-335-5p and its target gene intercellular adhesion
      molecule 1 (ICAM-1) in thyroid cancer. Real-time polymerase chain reaction (PCR)
      results showed that the expression level of ICAM-1 in cancer tissues was higher
      than that in their adjacent tissues. The expression level of ICAM-1 in papillary
      thyroid carcinoma was also significantly higher than that in other types of
      tumors. However, the expression of miR-335-5p is opposite to that of ICAM-1. In
      human thyroid cancer cell lines TPC-1, FTC-133, TT and human thyroid follicular
      cell line Nthyori 3-1, the expression level of ICAM-1 in TPC-1 was significantly
      higher than that of other cells, while the expression level of miR-335-5p in TPC
      1 was significantly lower than that of other cells. When ICAM-1 expression was
      downregulated and miR-335-5p expression was upregulated in TPC-1 cells, ICAM-1
      expression was upregulated and miR-335-5p expression was downregulated in FTC-133
      cells, we found that ICAM-1 could promote the proliferation of thyroid cancer
      cells, while miR-335-5p could inhibit the proliferation of thyroid cancer cells.
      miR-335-5p could combine with 3'UTR of ICAM-1 by bioinformatics prediction.
      Luciferase reporter gene analysis and Western blotting detection further
      confirmed that miR-335-5p could target ICAM-1 and inhibit its expression. The
      expression level of miR-335-5p was downregulated, while the expression level of
      ICAM-1 was upregulated in thyroid cancer. This study will help us better
      understand the pathogenesis of thyroid cancer and provide new insights into the
      treatment of this disease.

PMID- 30119272
TI  - Expanding the use of bilateral internal thoracic artery: Yes! We can.

PMID- 30119271
TI  - Diabetes and hepatocellular carcinoma: A pathophysiological link and
      pharmacological management.
AB  - Both diabetes mellitus (DM) and cancer are multifarious, dissimilar, and long
      lasting, fatal diseases with a remarkable influence on health worldwide. DM is
      not only related to cardiovascular diseases, neuropathy, nephropathy, and
      retinopathy, but also related to a number of liver diseases such as nonalcoholic
      fatty liver disease, steatohepatitis, and liver cirrhosis. Recently, it is
      hypothesized that DM has a greater risk for many forms of cancer, such as breast,
      colorectal, endometrial, pancreatic, gallbladder, renal, and liver cancer
      including hepatocellular carcinoma (HCC). Both DM and cancer have many common
      risk factors, but the association between these two is poorly stated. Several
      epidemiologic studies have revealed the association between pathogenic and
      prognostic characteristics of DM and a higher incidence of HCC, thus representing
      DM as an independent risk factor for HCC development. The etiological and
      pathophysiological relationship between DM and HCC has been presented in this
      review by linking hyperglycemia, hyperinsulinemia, insulin resistance, and
      activation of insulin-like growth factor signaling pathways and pharmacological
      management of HCC associated with DM.

PMID- 30119273
TI  - Bilateral internal thoracic artery use: Closing the knowledge gap.

PMID- 30119274
TI  - Sixteen years later and the debate for transcatheter aortic valve replacement or
      surgical aortic valve replacement remains controversial.

PMID- 30119275
TI  - Fixing the supply problem.

PMID- 30119276
TI  - Left atrial appendage occlusion in research and in real-world practice.

PMID- 30119277
TI  - We must amputate!?

PMID- 30119278
TI  - "Appending" onto left-sided thoracoscopic operations: An obvious two-for-one
      bargain?

PMID- 30119279
TI  - Vancomycin paste still does not reduce the incidence of deep sternal wound
      infection after cardiac surgery.

PMID- 30119280
TI  - Vancomycin paste and deep sternal wound infections-Deja vu all over again.

PMID- 30119281
TI  - Vancomycin paste in sternal wound infection prophylaxis-a genuine debate or
      futile attempts to justify flawed study?

PMID- 30119282
TI  - Left atrial pressure measurement in a rat is currently impossible due to size
      limitations of balloon occlusion catheter.

PMID- 30119283
TI  - Direct measurement of left atrial and pulmonary artery pressure in rats with
      pulmonary hypertension.

PMID- 30119284
TI  - Oral thyroxin supplementation in infants undergoing cardiac surgery: A double
      blind placebo-controlled randomized clinical trial.
AB  - BACKGROUND: Decreases in serum total thyroxin and total triiodothyronine occurs
      after cardiopulmonary bypass, and is reflected as poor immediate outcome. We
      studied effects of oral thyroxin supplementation in infants who underwent open
      heart surgery. METHODS: In this prospective study, 100 patients were randomized
      into 2 groups: 50 in the thyroxin group (TH) and 50 in the placebo group (PL).
      Patients in the TH group received oral thyroxin (5 MUg/kg) 12 hours before
      surgery and once daily for the remainder of their intensive care unit (ICU) stay.
      Data on intraoperative and postoperative variables were recorded. Cardiac index
      (CI) was measured. Perioperative serum thyroid hormone levels and serum
      interleukin-6 and tumor necrosis factor-alpha were measured. Secondary analysis
      was performed by dividing patients into simple and complex subcategories.
      RESULTS: Results of the primary analysis indicated a higher CI in the TH compared
      with the PL. In the complex category, the mean duration of mechanical ventilation
      was 3.85 +/- 0.93 and 4.66 +/- 1.55 days in the TH and PL, respectively (P =
      .001). Mean ICU stay was 6.79 +/- 2.26 and 8.33 +/- 3.09 days (P = .03), and mean
      hospital stay was 15.70 +/- 4.77 and 18.90 +/- 4.48 days (P = .01) in the TH and
      PL, respectively. There were no significant differences between the TH and the PL
      in the simple category. CI was higher in the TH at all time points (P = .004).
      The average therapeutic intervention scoring system scores for the first 2 days
      were higher in the PL in the complex category. CONCLUSIONS: Oral thyroxin
      supplementation improves the CI and reduces the inotropic requirement. In
      addition, it reduces the duration of mechanical ventilation, ICU and hospital
      stay, and therapeutic intervention scoring system in infants after surgery for
      complex congenital heart defects.

PMID- 30119285
TI  - Cutting off the lizard's tail in surgery.

PMID- 30119286
TI  - When an analogy has reached the extent of its usefulness.

PMID- 30119288
TI  - Discussion.

PMID- 30119287
TI  - Treatment trends in early-stage lung cancer in the United States, 2004 to 2013: A
      time-trend analysis of the National Cancer Data Base.
AB  - OBJECTIVE: The study objective was to evaluate trends in the use of surgical
      therapy for patients with early-stage (IA-IIA) non-small cell lung cancer when
      stereotactic ablative radiotherapy was introduced in the United States. METHODS:
      Patients with clinical stage IA to IIA non-small cell lung cancer diagnosed from
      January 1, 2004, to December 31, 2013, were identified in the National Cancer
      Data Base. The Cochran-Armitage trend test was used to evaluate the change in the
      proportion of patients undergoing surgery over time. Logistic regression was used
      to identify the factors associated with receipt of surgery compared with
      radiation. RESULTS: Of 200,404 eligible patients from 1235 hospitals, 79.8% (n =
      159,943) underwent surgery. For all stages combined, the rate of surgery
      decreased from 83.9% in 2004 to 75.1% in 2013 (P < .0001), with the largest
      decrease seen in patients with stage IIA: stage IA 86.5% to 77.1% (P < .0001);
      stage IB 79.6% to 71.5% (P < .0001); and stage IIA 94.7% to 70.3% (P < .001).
      Patients were more likely to undergo surgery if they were younger and white, had
      higher income, or had private or Medicare insurance. CONCLUSIONS: From 2004 to
      2013, there was an overall decrease in the use of surgical therapy for lung
      cancer in early-stage disease. Because resection remains the standard of care for
      most patients with early-stage disease, these data suggest a potentially
      significant quality gap in the treatment of patients with non-small cell lung
      cancer.

PMID- 30119289
TI  - Not all malignant pleural effusions are created equal.

PMID- 30119290
TI  - Cardiac amyloidosis in aortic stenosis: The tip of the iceberg.

PMID- 30119291
TI  - Cardiac amyloidosis in aortic stenosis-icebergs and Archimedes' principle.

PMID- 30119292
TI  - Alpha-stat versus pH stat acid base balance for aortic arch surgery: The debate
      continues.

PMID- 30119293
TI  - Overexpression of TUSC7 inhibits the inflammation caused by microglia activation
      via regulating miR-449a/PPAR-gamma.
AB  - OBJECTIVE: The aim of this study was to investigate the mechanisms of TUSC7/miR
      449a/PPAR-gamma axis on the inflammation induced by microglia activation.
      METHODS: A compressive spinal cord injury (SCI) model was established. The
      expressions of TUSC7, miR-449a PPAR-gamma, TNF-alpha and IL-1beta in spinal cord
      tissues of SCI rats and HAPI cells were determined. The interaction of TUSC7 and
      miR-449a was tested by RIP and RNA pull-down assays. The regulatory relationship
      between miR-449a and PPAR-gamma was tested by dual luciferase reporter gene
      assay. RESULTS: In the spinal cord tissue of SCI rats and HAPI cells induced by
      LPS, TUSC7 expression was reduced and miR-449a expression was increased.
      Overexpression of TUSC7 inhibited microglial activation and the expression of
      inflammatory factors (TNF-alpha and IL-1beta). Moreover, we have found a
      targeting regulatory relation between TUSC7 and miR-449a, and a negative
      regulatory relationship between miR-449a and PPAR-gamma. In the study of
      molecular mechanism, we found that TUSC7 could regulate PPAR-gamma through miR
      449a, and overexpression of TUSC7 inhibited microglial activation and the
      expression of inflammatory factors through miR-449a. CONCLUSION: Overexpression
      of TUSC7 inhibited microglial activation and the expression of inflammatory
      factors in microglia cells by regulating miR-449a/PPAR-gamma.

PMID- 30119294
TI  - Generation of random numbers by measuring phase fluctuations from a laser diode
      with a silicon-on-insulator chip.
AB  - Random numbers are a fundamental resource in science and technology. Among the
      different approaches to generating them, random numbers created by exploiting the
      laws of quantum mechanics have proven to be reliable and can be produced at
      enough rates for their practical use. While these demonstrations have shown very
      good performance, most of the implementations using free-space and fibre optics
      suffer from limitations due to their size, which strongly limits their practical
      use. Here we report a quantum random number generator based on phase fluctuations
      from a diode laser, where the other required optical components are integrated on
      a mm-scale monolithic silicon-on-insulator chip. The post-processing reported in
      this experiment is performed via software. However, our physical device shows the
      potential of operation at generation rates in the Gbps regime. Considering the
      device's size, its simple, robust and low power operation, and the rapid
      industrial uptake of silicon photonics, we foresee the widespread integration of
      the reported design in more complex systems.

PMID- 30119295
TI  - First demonstration of a 400 Gb/s 4lambda CWDM TOSA for datacenter optical
      interconnects.
AB  - We present the first demonstration of a 4lambda transmitter optical sub-assembly
      (TOSA) on the coarse wavelength division multiplexing (CWDM) grid, i.e., 20 nm
      spacing, targeting 400G-FR4 requirements over 2 km. The TOSA is based on uncooled
      InP external modulated laser (EML) technology and it utilizes four EMLs followed
      by a CWDM multiplexer. We characterize the performance of the TOSA versus
      received optical modulation amplitude (OMA), number of equalizer taps, reach,
      modulation format, TOSA case temperature, and bit rate. Four 53 Gbaud 4-level
      pulse amplitude modulation (PAM4) RF signals are used to drive the TOSA achieving
      a net rate of 400 Gb/s. Results reveal that 400 Gb/s can be transmitted over 2 km
      of single mode fiber (SMF) at a bit error rate (BER) below the KP4- forward error
      correction (KP4-FEC) threshold (i.e., 2.4 * 10-4) using only a 5 tap feed forward
      equalizer at the receiver. To the best of our knowledge, this is the first
      demonstration of 400 Gb/s using a 4lambda CWDM TOSA over 2 km of SMF. Moreover,
      we achieve 400 Gb/s and 600 Gb/s over 20 km and 10 km below KP4-FEC and the 7%
      hard-decision FEC (HD-FEC) (i.e., 3.8 * 10-3) thresholds, respectively, without
      optical amplification. Furthermore, we show the performance of the TOSA against
      temperature, where it shows no significant change in the BER performance from 20 
      degrees C to 60  degrees C. Finally, we compare the performance of PAM2, PAM4,
      and PAM8 modulation formats where we show the possibility of achieving 400 Gb/s
      aggregate bit rate using 42 Gbaud PAM8 modulation format at the expense of
      utilizing a stronger FEC.

PMID- 30119296
TI  - Space-time multichannel adaptive filtering scheme for VLC color cross-talk
      equalization.
AB  - In the emerging framework of visible light communications, the limitation of
      modulation bandwidth of light emitting diodes (LEDs) transmitters is
      counterbalanced by the use of red-green-blue (RGB) LEDs since they exhibit higher
      modulation bandwidth. Using RGB LEDs allows to exploit the spatial multiplexing
      aspects, that is obtaining parallel channels for transmission. In this context,
      we used at the receiver RGB-tuned photodiodes (PDs). Hence each PD can, in
      principle, detect only the information its tuning is matched to. The drawback of
      increasing spectral efficiency is the presence of cross-talk at the single PD due
      to the signals emitted by the remaining colors when a perfect color filtering is
      not applied. In this paper we consider amplitude shift keying (ASK) modulation,
      investigate the issue of the spatial (color) interference and we present a blind
      multichannel adaptive equalizer able to mitigate the temporary intersymbol
      interference (ISI) and also the spatial (color) ISI, this latter partially
      suppressed using suitable color filters. We analyze also the convergence of the
      adaptive algorithm and compare its performance with the literature.

PMID- 30119297
TI  - Performance analysis of space multiplexing by superposed signal in multi
      dimensional VLC system.
AB  - This paper first brings a single receiver multiple-input-multiple-output (SR
      MIMO) model to realize the space multiplexing in the visible light communication
      (VLC) system. The signals from two transmitters are super-imposed in the receiver
      thus to realize a specially superposed modulation. Depending on the power ratio
      between two transmitters, various superposed signal structures can be obtained.
      In order to separate the superposed signal, we design a novel detection algorithm
      which consists of the successive interference cancellation (SIC) and the look-up
      table (LUT). Extensive experiments demonstrate that a data rate of 1.5Gbit/s is
      achieved in the 1.3-m indoor line-of-sight (LOS) scenario with the bit error
      rates (BERs) are below the forward error correction (FEC) threshold.

PMID- 30119298
TI  - Denoising Poisson phaseless measurements via orthogonal dictionary learning.
AB  - Phaseless diffraction measurements recorded by CCD detectors are often affected
      by Poisson noise. In this paper, we propose a dictionary learning model by
      employing patches based sparsity in order to denoise such Poisson phaseless
      measurements. The model consists of three terms: (i) A representation term by an
      orthogonal dictionary, (ii) an L0 pseudo norm of the coefficient matrix, and
      (iii) a Kullback-Leibler divergence term to fit phaseless Poisson data. Fast
      alternating minimization method (AMM) and proximal alternating linearized
      minimization (PALM) are adopted to solve the proposed model, and especially the
      theoretical guarantee of the convergence of PALM is provided. The subproblems for
      these two algorithms both have fast solvers, and indeed, the solutions for the
      sparse coding and dictionary updating both have closed forms due to the
      orthogonality of learned dictionaries. Numerical experiments for phase retrieval
      using coded diffraction and ptychographic patterns are conducted to show the
      efficiency and robustness of proposed methods, which, by preserving texture
      features, produce visually and quantitatively improved restored images compared
      with other phase retrieval algorithms without regularization and local sparsity
      promoting algorithms.

PMID- 30119299
TI  - 302 W quasi-continuous cascaded diamond Raman laser at 1.5 microns with large
      brightness enhancement.
AB  - We report a second Stokes diamond Raman laser at 1.49 MUm capable of high power
      and large-scale-factor brightness enhancement. Using a quasi-continuous 1.06 MUm
      pump of power 823 W (0.85% duty cycle) and M2 up to 6.4, a maximum output power
      of 302 W was obtained with an M2 = 1.1 providing an overall brightness
      enhancement factor of 6.0. The pulse length of ~210 MUs was selected to ensure
      operation was representative of steady-state continuous lasing conditions in the
      diamond bulk. Accompanying theoretical calculations indicate that even more
      strongly aberrated pumps may be used to efficiently generate high beam quality
      output and with higher brightness enhancement factors. This diamond-based beam
      conversion technique addresses needs for high brightness and efficient eye-safe
      sources using low-brightness 1 MUm pumps and reveals a widely-applicable route to
      practical high brightness lasers of increased wavelength range.

PMID- 30119300
TI  - Fast demodulation of OFDR based long length FBG sensing system for noisy signals.
AB  - The high spatial resolution, high accuracy, as well as real-time capability of
      distributed fiber-optic sensors are important for real-time structural health
      monitoring. As one of the promising technologies, the optical frequency domain
      reflectometry (OFDR) based sensors, have attracted lots of attention. Currently,
      for the demodulation, the conventional method based on short time Fourier
      transform requires long computational time, while a recent method based on group
      delay can remarkably improve the calculation speed but has low noise tolerance.
      In this study, we propose a fast demodulation method which employs the cross
      correlation, weighted sliding windowed Fourier transform and logistic activation
      function based thresholding process. This approach keeps good balance among the
      high spatial resolution, high accuracy, and the real-time capability that is
      expected to further improve the applicability of OFDR based sensors.

PMID- 30119301
TI  - Scattering-loss reduction of ridge waveguides by sidewall polishing.
AB  - Ridge waveguides provide a large refractive index contrast and thus strong mode
      confinement, making them highly attractive for building compact photonic
      integrated circuits. However, ridge waveguides suffer from scattering losses. We
      demonstrate scattering-loss reduction of ridge waveguides made of lithium-niobate
      on-insulator (LNOI) substrates by more than one order of magnitude. This is
      achieved by gently polishing of the ridge's sidewalls and simultaneous protection
      of the top surfaces by a metal layer. Whispering-gallery-resonator loss
      measurements reveal ultra-low losses down to 0.04 dB/cm of the processed
      waveguides. Our approach pushes ridge waveguides further towards their
      fundamental absorption-loss limit, enabling highly efficient integrated devices.

PMID- 30119302
TI  - Elliptical polarization for molecular Stark shift compensation in deep optical
      traps.
AB  - In optical dipole traps, the excited rotational states of a molecule may
      experience a very different light shift than the ground state. For particles with
      two polarizability components (parallel and perpendicular), such as linear 1Sigma
      molecules, the differential shift can be nulled by choice of elliptical
      polarization. When one component of the polarization vector is +/-i2 times the
      orthogonal component, the light shift for a sublevel of excited rotational states
      +/-approaches that of the ground state at high optical intensity. In this case,
      fluctuating trap intensity need not limit coherence between ground and excited
      rotational states.

PMID- 30119303
TI  - Roll angle measurement system based on differential plane mirror interferometer.
AB  - A precision roll angle measurement system based on differential plane mirror
      interferometer (DPMI) is proposed and the measurement principle has been analyzed
      theoretically in detail. This system uses DPMI with wedgy angle prism and wedgy
      angle reflector to produce diagonal symmetry of the two frequency beams. The
      residual of nanopositioning stage and roll angle system is less than 1 MUrad,
      which has verified the correctness of the measuring principle. As result, the
      stability of the roll angle measurement system is satisfactory, and the average
      deviation of measurement experiments is less than 5 MUrad.

PMID- 30119304
TI  - Torsion sensor based on inter-core mode coupling in seven-core fiber.
AB  - We proposed a novel torsion sensor based on inter-core mode coupling in seven
      core fiber (SCF). The torsion sensor is fabricated by tapering a commercially
      available SCF spliced with two single mode fibers. Waist diameter and length of
      the taper structure were experimentally optimized to achieve good transmission
      spectrum. Based on this structure, the torsion measurement was conducted, and the
      experimental results demonstrated that the transmission spectrum shows a red
      shift with the fiber twist. The torsion sensitivity increases with the twisting
      angle, which can achieve as high as 1.00 nm/ degrees . The direction of
      wavelength shift was observed to be opposite when twisting the tapered SCF in
      clockwise and counter-clockwise direction, demonstrating its capability to
      discriminate the rotation orientation. Moreover, all the measurements were
      repeated in attempts to confirm its stable performance as well as high accuracy.
      Mode coupling dynamics and theory of optical anisotropy in twisted fiber are
      adopted to discuss the sensitivity performance, which agrees well with
      experimental results. The novel torsion sensor could provide a promising
      candidate for the applications requiring accurate rotation.

PMID- 30119305
TI  - Realization of true all-optical AND logic gate based on nonlinear coupled air
      hole type photonic crystal waveguides.
AB  - In this manuscript we propose an easily scalable true all-optical AND logic gate
      for pulsed signal operation based on band-gap transmission within nonlinear
      realistic air-hole type coupled photonic crystal waveguides (C-PCW). We call it
      "true" all-optical AND logic gate, because all AND gate topologies operate with
      temporal solitons that maintain a stable pulse envelope during the optical signal
      processing along the different C-PCW modules yielding ultrafast full-optical
      digital signal processing. We directly use the registered (output) signal pulse
      as new input signal between multiple concatenated nonlinear C-PCW modules (i.e.
      AND gates) to setup a multiple-input true all-optical AND logic gate. Extensive
      full-wave computational electromagnetic analysis proves the correctness of our
      theoretical studies and the proposed operation principle of the multiple-input
      AND logic gate is vividly demonstrated for realistic C-PCWs.

PMID- 30119306
TI  - Phase-sensitive amplifier link with distributed Raman amplification.
AB  - We demonstrate long-haul transmission using a hybrid amplifier approach combining
      distributed Raman amplification and lumped phase-sensitive amplification. Aside
      from the well-known resulting SNR improvement, distributed Raman amplification is
      included in an effort to improve the nonlinearity mitigation capability of the
      phase-sensitive amplifiers. When changing from phase-insensitive operation to
      phase-sensitive operation in a link employing distributed Raman amplification,
      the transmission reach at BER = 10-3 is increased from 15 to 44 spans of length
      81 km while simultaneously increasing the optimal launch power by 2 dB.

PMID- 30119308
TI  - Vertical liquid controlled adiabatic waveguide coupler.
AB  - A broadband vertical liquid controlled optical waveguide coupler (LCC) is
      demonstrated. The fabricated vertical LCC with silicon nitride (SiN) waveguides
      can switch light between 2 stacked photonic circuit layers with zero energy
      consumption in a steady switch state. In combination with low-loss interlayer
      waveguide crossovers they enable large scale non-volatile switch circuits with
      low loss. The fabricated vertical LCC has a loss less than 2.0 dB in bar state
      and less than 2.6 dB in cross state over the telecommunication wavelength range
      1260 nm to 1630 nm. Interlayer waveguide crossovers with the same interlayer
      oxide thickness as the LCC have a loss less than 0.06 dB over the same wavelength
      range. The crosstalk of the LCC is less than -21 dB over the wavelength range
      1500 nm to 1630 nm for both bar and cross state.

PMID- 30119307
TI  - Multi-modal chip-based fluorescence and quantitative phase microscopy for
      studying inflammation in macrophages.
AB  - Total internal reflection fluorescence (TIRF) microscopy benefits from high
      sensitivity, low background noise, low photo-toxicity and high-contrast imaging
      of sub-cellular structures close to the membrane surface. Although, TIRF
      microscopy provides high-contrast imaging it does not provide quantitative
      information about morphological features of the biological cells. Here, we
      propose an integrated waveguide chip-based TIRF microscopy and label-free
      quantitative phase imaging (QPI). The evanescent field present on top of a
      waveguide surface is used to excite the fluorescence and an upright microscope is
      used to collect the signal. The upright microscope is converted into a Linnik
      type interferometer to sequentially extract both the quantitative phase
      information and TIRF images of the cells. Waveguide chip-based TIRF microscopy
      benefits from decoupling of illumination and collection light path, large field
      of view imaging and pre-aligned configuration for multi-color TIRF imaging. The
      proposed multi-modal microscopy is used to study inflammation caused by
      lipopolysaccharide (LPS) on rat macrophages. The TIRF microscopy showed that LPS
      inflammatory molecule disrupts the cell membrane and causes cells to
      significantly expand across a substrate. While, QPI module quantified changes in
      the sub-cellular content of the LPS challenged macrophages, showing a net
      decrease in its maximum phase values.

PMID- 30119309
TI  - Surface sensing with integrated optical waveguides: a design guideline.
AB  - Waveguide-based biochemical sensors exploit detection of target molecules that
      bind specifically to a functionalized waveguide surface. For optimum sensitivity,
      the waveguide should be designed to mediate maximum influence of the surface
      layer on the effective refractive index of the guided mode. In this paper, we
      define a surface sensitivity metric which quantifies this impact and which allows
      to broadly compare different waveguide types and integration platforms. Focusing
      on silicon nitride and silicon-on-insulator (SOI) as the most common material
      systems, we systematically analyze and optimize a variety of waveguide types,
      comprising simple strips, slot and double slot structures, as well as sub
      wavelength gratings (SWG). Comparing the highest achievable surface
      sensitivities, we provide universal design guidelines and physically interpret
      the observed trends and limitations. Our findings allow to select the appropriate
      WG platform and to optimize sensitivity for a given measurement task.

PMID- 30119310
TI  - Dual-phase-modulated plug-and-play measurement-device-independent continuous
      variable quantum key distribution.
AB  - We suggest a novel scheme for measurement-device-independent (MDI) continuous
      variable quantum key distribution (CVQKD) by integrating plug-and-play (PP)
      configuration with dual-phase modulation (DPM). With these techniques, MDI-CVQKD
      system has the ability to overcome a number of impractical problems with no extra
      performance penalty. In particular, the synchronous loophole of different lasers
      from Alice and Bob can be elegantly eliminated in the plug-and-play
      configuration, which gives birth to the convenient implementation when comparing
      to the Gaussian-modulated coherent-state protocol. Moreover, All LO-aimed attacks
      can be well defended since the local oscillator (LO) is locally generated. By
      taking advantage of DPM, the performance degeneration caused by the practical
      polarization-sensitive amplitude modulator can be eliminated. We also derive the
      security bounds for the proposed scheme against optimal Gaussian collective
      attacks. By taking the finite-size effect into account, we show that almost all
      raw keys generated by the proposed scheme can be exploited for the final secret
      key generation so that the secret key rate can be increased without sacrificing a
      part of raw keys for parameter estimation. In addition, we give an experimental
      concept of the proposed scheme which can be deemed guideline for final
      implementation.

PMID- 30119311
TI  - Dynamic interference as signature of atomic stabilization.
AB  - We study the ionization of atoms by very intense linearly polarized pulse with
      moderately high frequency by numerically solving the time-dependent Schrodinger
      equation (TDSE). In this regime, the photon energy exceeds the ionization
      potential allowing for one-photon ionization which is, however, strongly
      influenced by strong nonlinear photon-atom interactions. We find that the onset
      of atomic stabilization can be monitored by the appearance of a dynamic
      interference pattern in the photoelectron spectrum.

PMID- 30119312
TI  - Intense, directional and tunable gamma-ray emission via relativistic oscillating
      plasma mirror.
AB  - A mechanism for high energy gamma-photon generation based on laser-plasma
      accelerator is proposed. The laser pulse with a peak intensity of 1022W/cm2
      accelerates the electron beam to GeV by the laser wakefield effect. A solid
      Aluminium target serves as a plasma mirror which is located at the rear side of a
      gas jet and reflects the laser pulse. High order harmonics are generated due to
      the Doppler effect experienced by the incident laser. The collisions of the
      reflected attosecond pulses and the energetic electron beam provide a large cross
      section for nonlinear Compton scattering and produce a collimated gamma-photon
      flux. The mechanism generates GeV photons with a pulse duration given by the
      duration of the electron beam.

PMID- 30119313
TI  - 1 * 8 MMI based multi-channel interference laser integrated with SOA through a 2
      port multimode interference reflector.
AB  - A 1 * 8 multimode interferometer (MMI) based multi-channel interference (MCI)
      widely tunable laser integrated with semiconductor optical amplifier (SOA)
      through a 2-port multimode interference reflector (MIR) is reported in this
      paper. The 2-port MIR can be fabricated with deeply etched waveguides of the MCI
      laser with no extra fabrication process, which decreases the fabrication
      complexity greatly. To reduce the loss arising from mode mismatch between surface
      and deep ridge waveguides, a tapered shallow-deep transition structure is
      designed and fabricated with a loss of 0.09 dB +/- 0.03 dB. The MCI laser with
      integrated SOA achieves a tuning range of 52.5 nm with side mode suppression
      ratios higher than 40 dB across the tuning range and more than 13 dBm output
      power coupled into a lensed fiber at room temperature.

PMID- 30119314
TI  - Time-lens perspective on fiber chirped pulse amplification systems.
AB  - Time-lens is an analogy of the conventional lens in the time-domain, which
      constitutes a source of inspiration to design and implement optical systems based
      on concepts borrowed from the well-established field of Fourier optics. We
      propose a design method of chirped pulse amplification systems based on this
      analogy. In this simple physics picture, the relation between dispersion and
      nonlinear phase shift under gain saturation can be obtained in a straightforward
      way. We demonstrate that this simple model agrees well with experimental results.
      It is a simple, effective and practical design method for chirped pulse
      amplification systems, especially for ultrafast fiber amplification systems.

PMID- 30119315
TI  - Density-dependent determination of scattering properties of pharmaceutical
      tablets using coherent backscattering spectroscopy.
AB  - We report on measurements of coherent backscattering from pharmaceutical tablets.
      Experimental data is analysed using the radiative transfer equation with focus on
      the determination of the reduced scattering coefficient MUs'. The results show a
      good agreement with MUs' determined by measuring the spatially resolved
      reflectance, whereat we demonstrate advantages of the coherent backscattering
      measurements. Furthermore, we present a correlation between MUs' and tablet
      compression force, respectively density.

PMID- 30119316
TI  - Performance analysis of multiple NLOS UV communication cooperative relays over
      turbulent channels.
AB  - Ultraviolet (UV) communication overcomes pointing and tracking errors and is
      superior to other modern optical wireless communication technologies at short
      range. Using effective wavelengths from 200 to 280 nm, enables the non-line-of
      sight (NLOS) outdoor UV communication in the presence of strong molecular and
      aerosol scattering. Because of these characteristics, solar blind NLOS UV
      communications offers broad coverage and high security. In this paper, NLOS UV
      communication is considered with decode and forward (DF) relays in the presence
      of log-normal (LN) channels using the best relay selection technique according to
      the channel state information (CSI). Then the outage probability of the multi
      relay UV system is discussed for the proposed model. Simulation results verify
      the effectiveness of our employed analytical model. The outage probability for
      both serial and cooperative relays is compared with a different number of relays.
      Numerical simulations are further presented for many factors influencing the
      functioning of the system such as elevation angle, atmospheric scattering
      parameters and receiver field of view (FOV) angles. The obtained results
      demonstrate that increasing the number of UV NLOS cooperative relays does not
      necessarily improve the system performance, but there are other factors that must
      be considered such as the value of the elevation angle and the number of relays.

PMID- 30119317
TI  - Depth-driven variable-frequency sinusoidal fringe pattern for accuracy
      improvement in fringe projection profilometry.
AB  - Sinusoidal fringe pattern is widely used in optical profilometry; however, the
      traditional constant-frequency sinusoidal fringe pattern reduces 3D measurement
      accuracy in the defocus region. To this end, this paper presents a variable
      frequency sinusoidal fringe pattern method that is optimized by the measurement
      depth. The proposed method improves the pixel matching accuracy and thus
      increases measurement accuracy. This paper theoretically determines the optimal
      frequency by analyzing the pixel matching error caused by intense noise in a
      captured image; presents the online frequency optimization along abscissa and
      ordinate axes in the sinusoidal fringe patterns; and details the encoding and
      decoding to use variable-frequency fringe patterns for 3D profilometry.
      Simulations and experiments demonstrate that our proposed method can improve the
      3D measurement accuracy and increase measurement robustness.

PMID- 30119318
TI  - Real-time single-pixel video imaging with Fourier domain regularization.
AB  - We present a closed-form image reconstruction method for single-pixel imaging
      based on the generalized inverse of the measurement matrix. Its numerical cost
      scales proportionally with the number of measured samples. Regularization of the
      inverse problem is obtained by minimizing the norms of the convolution between
      the reconstructed image and a set of spatial filters. The final reconstruction
      formula can be expressed in terms of matrix pseudoinverse. At high compression,
      this approach is an interesting alternative to the methods of compressive sensing
      based on l1-norm optimization, which are too slow for real-time applications. For
      instance, we demonstrate experimental single-pixel detection with real-time
      reconstruction obtained in parallel with measurement at a frame rate of 11 Hz for
      highly compressive measurements with a resolution of 256 * 256. To this end, we
      preselect the sampling functions to match the average spectrum obtained with an
      image database. The sampling functions are selected from the Walsh-Hadamard
      basis, from the discrete cosine basis, or from a subset of Morlet wavelets
      convolved with white noise. We show that by incorporating the quadratic criterion
      into the closed-form reconstruction formula, we can use binary rather than
      continuous sampling and reach similar reconstruction quality as is obtained by
      minimizing the total variation. This makes it possible to use cosine- or Morlet
      based sampling with digital micromirror devices without advanced binarization
      methods.

PMID- 30119319
TI  - Field-stitching boundary element method for accurate and rapid vectorial
      diffraction analysis of large-sized one-dimensional diffractive optical elements.
AB  - We propose a field-stitching boundary element method (FSBEM) for diffraction
      analyses for large diffractive optical elements (DOEs). A field stitching (FS)
      method separately computes the divided sections of a large DOE and provides the
      field distribution without field mismatching. However, a divided section must be
      largely overlapped, which is not efficient in terms of computational resources.
      In the FSBEM, in addition to spatial division, the electromagnetic field is
      computed for each component-the reflected, difference, and stitching fields-for
      rapid convergence of the solution. We validate the FSBEM by computing a one
      dimensional DOE and evaluating the convergence property. The sample structure is
      also computed by the conventional FS method, and the advantages of the FSBEM are
      discussed.

PMID- 30119320
TI  - Phase-locking of arrays of weakly coupled semiconductor lasers.
AB  - In this paper we study the conditions for achieving almost perfect phase locking
      in large arrays of semiconductor diodes. We show that decayed non-local coupling
      of diode lasers can provide the necessary conditions for robust phase
      synchronization of an entire diode laser array. Perfect global coupling is known
      to allow for robust synchronization, however it is often physically impossible or
      impractical to achieve. We show that when diodes are coupled via the decayed non
      local coupling layout, the dominant transverse mode of the laser array has a
      uniform phase across the lasers and can be stable. This state is robust to noise
      and frequency disorder and can be realized under periodic (fixed-intensity limit
      cycle) continuous-wave and chaotic behavior of lasers.

PMID- 30119321
TI  - Sharp bending and power distribution of a focused radially polarized beam by
      using silicon nanoparticle dimers.
AB  - Control and manipulation of radiation direction and directivity is highly
      desirable in future integrated optical circuits. Here, we investigate
      theoretically and numerically the scattering properties of a silicon nanosphere
      dimer illuminated by a focused radially polarized beam. As compared with single
      silicon nanospheres, a scattering peak with a significantly enhanced intensity
      and a dramatically reduced linewidth was observed in the scattering spectrum of
      the silicon nanosphere dimer. Relying on the multipole expansion method, it was
      revealed that the radiation at the scattering peak originates mainly from the
      total electric dipole and the magnetic quadrupole excited in the silicon
      nanosphere dimer. It was found that the radiation direction of the silicon dimer
      is parallel to its axis, implying a sharp (90 degrees ) bending of the radially
      polarized beam. In addition, the radiation directivity is significantly improved
      as compared with single silicon nanospheres because of the interference between
      the total electric dipole and magnetic quadrupole modes. For a homodimer composed
      of two identical silicon nanospheres, the scattering light is equally distributed
      in the two radiation directions. In comparison, the incident light is
      preferentially scattered to the small Si nanosphere for a heterodimer composed of
      two silicon nanospheres with different diameters. As a result, a unidirectional
      lateral scattering can be realized by using a single silicon nanosphere displaced
      appropriately from the focal point. Our findings are helpful for understanding
      the mode hybridization in silicon nanosphere dimers illuminated by a focused
      radially polarized beam and useful for designing photonic devices capable of
      manipulating the radiation direction and directivity of structured light.

PMID- 30119322
TI  - Accurate measurement of laser intensity using photoelectron interference in
      strong-field tunneling ionization.
AB  - Accurate determination of laser intensity is of fundamental importance to study
      various phenomena in intense laser-atom/molecule interactions. We theoretically
      demonstrate a scheme to measure laser intensity by examining the holographic
      structure originating from the interference between the direct and near-forward
      rescattering electrons in strong-field tunneling ionization. By adding a weak
      second-harmonic field with polarization orthogonal to the strong fundamental
      driving field, the interference pattern oscillates with the changing relative
      phases of the two-color fields. Interestingly, the amplitude of this oscillation
      in the photoelectron momentum spectrum depends on the parallel momentum. With the
      quantum-orbit analysis, we show that the amplitude of the oscillation minimizes
      when the time difference between the recollision and ionization of near-forward
      rescattering electron is half cycle of the fundamental driving field. This
      enables us to measure accurately the laser intensity by seeking the minimum of
      the oscillation amplitude. Moreover, we show that this minimum can be determined
      without scanning the relative phases, instead, by just monitoring the
      interference patterns for two relative phases. This facilitates the application
      of our scheme in experiment.

PMID- 30119323
TI  - Focus shaping of the radially polarized Laguerre-Gaussian-correlated Schell-model
      vortex beams.
AB  - In this paper, we introduce a new kind of partially coherent vector beam with
      special correlation function and vortex phase named radially polarized Laguerre
      Gaussian-correlated Schell-model (LGCSM) vortex beam as a natural extension of
      scalar LGCSM vortex beam. The realizability conditions for such beam are derived.
      The tight focusing properties of a radially polarized LGCSM vortex beam passing
      through a high numerical aperture (NA) objective lens are investigated
      numerically based on the vectorial diffraction theory. We find that not only the
      transverse component but also the longitudinal component of the focal field
      distributions can be shaped by regulating the structures of the correlation
      functions, which is quite different from that of the conventional radially
      polarized partially coherent beam. Moreover, a series of wildly used focal field
      with novel structure, e.g., focal spot, flat-topped or doughnut beam profiles,
      needle-like focal field and controllable three-dimensional (3D) optical cage,
      were obtained. These results indicate that the focus shaping can be achieved by
      combining the regulation of the structures of the correlation functions with the
      regulation of beam parameters effectively. Our results may be useful for
      potential applications in optical trapping, optical high-resolution microscopy
      and optical data storage.

PMID- 30119324
TI  - Reconstruction of multiple non-line-of-sight objects using back projection based
      on ellipsoid mode decomposition.
AB  - Non-line-of-sight imaging has attracted more attentions for its wide
      applications. Even though ultrasensitive cameras/detectors with high time
      resolution are available, current back-projection methods are still powerless to
      acquire a satisfying reconstruction of multiple hidden objects due to severe
      aliasing artifacts. Here, a novel back-projection method is developed to
      reconstruct multiple hidden objects. Our method considers decomposing all the
      ellipsoids in a confidence map into several "clusters" belonging to different
      objects (namely "ellipsoid mode decomposition"), and then reconstructing the
      objects individually from their ellipsoid modes by filtering and thresholding,
      respectively. Importantly, the simulated and experimental results demonstrate
      that this method can effectively eliminate the impacts of aliasing artifacts and
      exhibits potential advantages in separating, locating and recovering multiple
      hidden objects, which might be a good base for reconstructing complex non-line-of
      sight scenes.

PMID- 30119325
TI  - Excitation of direction-tunable surface plasmon polaritons by using a rectangular
      array of silver nanodisks.
AB  - Use of dipole-like localized surface plasmons (LSPs) induced on a rectangular
      array of silver nanodisks to excite directional surface plasmon polaritons (SPPs)
      on a flat silver film is demonstrated. By modifying the spectral resonance of the
      LSPs, an effective coupling of the incident light into the SPPs has been achieved
      at operational wavelength of lambda0 = 628 nm. The maximum SPP intensity exceeds
      25% of the incident intensity. Meanwhile, owing to the angle-dependent spatial
      distribution of the LSPs and the constructive interference between columns or
      rows of the array, the excited SPPs are supported to propagate in two orthogonal
      channels with a width of 1756 nm. Moreover, the propagation of the SPPs is
      tunable by rotating the polarization direction of the incident light between
      angles of 0 and pi/2. This approach of launching direction-tunable SPPs shows
      great potential in applications of integrated plasmonic circuits.

PMID- 30119326
TI  - Meters-long propagation of diffraction-free space-time light-sheets.
AB  - Space-time (ST) wave packets are pulsed beams in which the spatial frequencies
      and wavelengths are tightly correlated. Proper design of the functional form of
      these correlations results in diffraction-free and dispersion-free axial
      propagation; that is, propagation invariance in free space. To date, observed
      propagation distances of such ST wave packets has been on the order of a few
      centimeters. Here we synthesize an ST wave packet in the form of a pulsed optical
      sheet of transverse spatial width ~200 MUm and spectral bandwidth of ~2 nm, and
      observe its diffraction-free propagation for approximately 6 meters. For such ST
      wave packets, we identify the spectral uncertainty - the precision in associating
      the spatial and temporal frequencies - as a critical parameter in determining the
      propagation-invariant distance. We present a design strategy and an experimental
      methodology that enables further increase in the diffraction-free length.

PMID- 30119327
TI  - Electromagnetically induced transparency in a spin-orbit coupled Bose-Einstein
      condensate.
AB  - The artificial field can be generated by properly arranging pulsed magnetic
      fields interacting with a Bose-Einstein condensate (BEC), which can be widely
      used to simulate the phenomena of traditional condensed matter physics, such as
      spin-orbit (SO) coupling and the neutral atom spin Hall effect. The introduction
      of SO coupling in a BEC will alter its optical properties. Eletromagnetically
      induced transparency (EIT) is a powerful tool that can change and detect the
      properties of an atomic medium in a nondestructive way. It is important and
      interesting to study EIT properties and to investigate the effects of SO coupling
      on EIT. In this paper, we investigate EIT in a SO-coupled BEC. Not only is the
      transparency existing, but the real and imaginary parts of the susceptibility
      have an additional red frequency shift, which is linearly proportional to the
      strength of the SO coupling. By using this unconventional, sensitive EIT
      spectrum, SO coupling can be detected and its strength can be accurately measured
      according to the frequency shift.

PMID- 30119328
TI  - Wide-angle optical half-wave plate from the field transformation approach and
      form-birefringence theory.
AB  - In this paper, we theoretically design and analyse a wide-angle optical half-wave
      plate by combining the field transformation (FT) approach with the form
      birefringence theory. The FT method is a general approach to manipulate
      electromagnetic wave propagations from pre-defined boundary conditions and
      artificial media by design. In theory, the approach is valid for both parallel
      and perpendicular polarizations. In practice, the resulting medium can be
      mimicked by a form-birefringent structure which has the same dispersion
      properties for a wide range of incident angles. A proof concept design for
      optical half-wave plate is designed for near-infrared operations. The
      transmittance of proposed device is greater than 0.8 with a polarized state
      change under 75 degrees  oblique incidence.

PMID- 30119329
TI  - Multi-polarization passive millimeter-wave imager and outdoor scene imaging
      analysis for remote sensing applications.
AB  - Polarimetric passive millimeter-wave (PMMW) measurements can provide additional
      information about scenes. We report on the development of a 94GHz Multi
      Polarization Scanning Imaging Radiometer (MPSIR) for outdoor imaging
      applications, and the polarization characteristic analysis of experimentally
      acquired images. The imager angular resolution is measured to be 0.37 degrees ,
      and the thermal sensitivity is about 0.46K. Multi-polarization measurements are
      realized by rotating the detector around the observation axis direction. Several
      outdoor complex scenes are selected to passive image, which include the outdoor
      parking lot and the dormitory buildings in the woods. Various polarization
      parameter images are generated to analyze the polarization characteristics. Based
      on the multi-polarization imaging, eight more polarization parameters are created
      and they are all have the special distribution properties. The experimental
      results indicate that the multi-polarization imaging and the modified
      polarization parameters have the great potential for three-dimensional
      reconstruction, edge detection and image segmentation.

PMID- 30119330
TI  - Enhanced-generation of atom-photon entanglement by using FPGA-based feedback
      protocol.
AB  - The enhanced-generation of entanglement between one atomic collective excitation
      and a single photon (atom-photon) is very important for practical quantum
      repeaters and quantum networks based on atomic ensembles and linear optics. We
      present a feedback-loop algorithm based on field programmable gate array (FPGA)
      to obtain 21.6-fold increase of the generation rate of atom-photon entanglement
      at the storage time of 51 MUs comparing with no feedback protocol. The generation
      rate of the atom-photon entanglement is ~3190/s (2100/s) for the excitation
      probability of 1.65% at the storage time of 1 MUs (51 MUs). The Bell parameter
      and the fidelity of atom-photon entanglement at the storage time of 1 MUs are
      2.40 +/- 0.02 and 85.5% +/- 0.6%, respectively. The detailed FPGA-based feedback
      loop algorithm can be flexibly extended to the multiplexing of atom-photon
      entanglement, which is expected to further increase the generation rate of atom
      photon entanglement.

PMID- 30119331
TI  - Mie resonance induced broadband near-perfect absorption in nonstructured graphene
      loaded with periodical dielectric wires.
AB  - In general, there is a fundamental trade-off between the operational bandwidth
      and the attainable absorption. So, obtaining broadband wave absorption of a low
      reference standard such as 90% is not very difficult. However, when trying to
      obtain higher absorption such as 99%, the bandwidth will drop dramatically. Here,
      we demonstrate that broadband near-perfect absorption of over 99% absorption with
      a 60% relative bandwidth can be obtained utilizing single-layered and
      nonstructured graphene loaded with periodical dielectric wires. The absorption
      mechanism originates from the coupling of Mie resonances in dielectric wires
      excited by the incident wave to the graphene plasmon resonances, which introduces
      two absorption contributions: direct near-field absorption in the graphene and
      radiative emission into the graphene.

PMID- 30119332
TI  - Controllable and selective single-mode lasing in polymer microbottle resonator.
AB  - We report a single-mode dye-doped polymer microbottle resonator (MBR) laser. The
      selective single-mode lasing from different order whispering gallery modes is
      achieved by precisely controlling the axial and radial coupling position between
      a tapered nanofiber and an MBR, respectively. The side-mode suppression ratio is
      above 20 dB. By doping different fluorescence dyes into the MBR, single-mode
      lasers at various colors are demonstrated.

PMID- 30119333
TI  - Repeatability analysis of one-dimensional angular-measurement-based stitching
      interferometry.
AB  - Recently we presented one-dimensional Angular-measurement-based Stitching
      Interferometry (ASI) technique for synchrotron mirror metrology coupling an
      autocollimator and a white light interferometer. In this work, we conduct a
      further study on the measurement repeatability of this technique under different
      conditions, e.g. different scanning time or lengths with/without system drift.
      The similarity between the angle measuring stitching technique in ASI and the
      slope integration technique in deflectometry is addressed. The analytic
      expression of the height repeatability is derived while the slope noise is a zero
      mean uncorrelated additive noise. In addition, we use a set of typical stationary
      signals from the autocollimator and the white light interferometer in a real
      experiment to simulate numerous virtual scans for the numerical calculation of
      the measurement repeatability under different measurement conditions. The
      simulation result predicts a link between the measurement repeatability and the
      scanning time with a constant speed. Moreover, it indicates that the major factor
      affecting the repeatability of our current ASI system is the system drift error.

PMID- 30119334
TI  - Resonant laser printing of bi-material metasurfaces: from plasmonic to photonic
      optical response.
AB  - Metasurfaces are nanostructured surfaces with engineered optical properties -
      currently impacting many branches of optics, from miniaturization of optical
      components to realizing high-resolution structural colors. The optical properties
      of metasurfaces can be traced to the individual meta-atoms, which set the nature
      of the optical response, e.g., plasmonic for metallic meta-atoms or photonic for
      dielectric meta-atoms. Combining multiple types of responses opens up new
      horizons in design of optical materials, but has so far been avoided due to the
      fabrication difficulties associated with constructing a metasurface composed of
      several meta-atom materials. Here, we present a multi-material design approach by
      optically post-processing a metasurface constructed from self-assembled
      polystyrene spheres coated with silver. Using our concept of resonant laser
      printing, we locally alter the initial plasmonic response of the meta-atoms to a
      pure photonic response. Our work constitutes a conceptually different way of
      designing metasurfaces and can pave the way for realizing multi-material
      metasurfaces on large areas while being cost effective.

PMID- 30119335
TI  - 12 mode, WDM, MIMO-free orbital angular momentum transmission.
AB  - Simultaneous MIMO-free transmission of 12 orbital angular momentum (OAM) modes
      over a 1.2 km air-core fiber is demonstrated. WDM compatibility of the system is
      shown by using 60, 25 GHz spaced WDM channels with 10 GBaud QPSK signals. System
      performance is evaluated by measuring bit error rates, which are found to be
      below the soft FEC limit, and limited by inter-modal crosstalk. The crosstalk in
      the system is analyzed, and it is concluded that it can be significantly reduced
      with an improved multiplexer and de-multiplexer.

PMID- 30119336
TI  - Autostereoscopic 3D display using directional subpixel rendering.
AB  - In this paper we present an autostereoscopic 3D display using a directional
      subpixel rendering algorithm in which clear left-right images are expressed in
      real time based on a viewer's 3D eye positions. In order to maintain the 3D image
      quality over a wide viewing range, we designed an optical layer that generates a
      uniformly distributed light field. The proposed 3D rendering method is simple,
      and each pixel processing can be performed independently in parallel computing
      environments. To prove the effectiveness of our display system, we implemented
      31.5" 3D monitor and 10.1" 3D tablet prototypes in which the 3D rendering is
      processed in the GPU and FPGA board, respectively.

PMID- 30119337
TI  - Magnon-induced transparency and amplification in ????-symmetric cavity-magnon
      system.
AB  - Recent research on parity-time- (????-) symmetric optical structures have
      exhibited great potential for achieving distinctive optical behaviour which is
      unattainable with ordinary optical systems. Here we propose a ????-symmetric
      cavity-magnon system consisting of active cavity mode strongly interacting with
      magnon to study magnon-induced transparency (MIT) and amplification (MIA) by
      exploiting recent microwave-cavity-engineered ferromagnetic magnons. We find that
      (i) due to the gain-induced enhancement of coherent coupling between the cavity
      field and the magnon, the transmitted probe power is remarkably enhanced about
      four orders of magnitude and the bandwidth also becomes much narrower, compared
      to passive cavity system. (ii) More importantly, the light transmission can be
      well controlled by adjusting the applied magnetic field without changing other
      parameters, and a Lorentzian-like spectra can be established between the
      transmitted probe power and the external magnetic field, which provides an
      additional degree of freedom to realize the coherent manipulation of optical
      transparency and amplification. Our results may offer an approach to make a low
      power magnetic-field-controlled optical amplifier in ????-symmetric cavity-magnon
      system.

PMID- 30119338
TI  - Liquid crystal metasurfaces on micropatterned polymer substrates.
AB  - Formation of photonic liquid crystal metasurfaces on rubbed polyimide substrates
      patterned by focused ion beam is demonstrated. Modulation of the surface
      anchoring conditions with periods from 1 to 6 micrometers gives rise to periodic
      deformation of the nematic liquid crystal director field. The exact periodicity
      is confirmed by the light diffraction measurements. Distinct colors originating
      from the specific zero-order diffraction spectra are observed and qualitatively
      explained in terms of an analytical model within the one-constant approximation.
      Quantitatively accurate optical spectra are obtained by the full scale numerical
      simulations taking into account all relevant material parameters. The results
      pave the way for hybrid liquid-crystal-based metasurfaces with tunable optical
      transmission, diffraction, and lasing.

PMID- 30119339
TI  - Weak-scattering static diffuser by fast pumping dispersed-nanoparticles in a long
      distance using microfluidic flows for efficient laser speckle reduction.
AB  - Changing diffusers are most commonly used for laser speckle reduction. Here, a
      weak-scattering static diffuser (WSSD) is proposed and demonstrated by fast
      pumping poly(methyl methacrylate) nanoparticles in a long distance using
      microfluidic flow. Experimental results show that this proof-of-concept device
      can effectively reduce speckle, where the lowest speckle contrast ratio is 0.04.
      Comparing with vibrating/rotating diffusers driven by mechanical motors for
      speckle reduction, the WSSD is static. Moreover, the WSSD can suppress speckle
      with weaker light scatterings (scattering angle equals to 5.8 degrees  at the
      lowest speckle contrast ratio value), making it superior to vibrating/rotating
      diffusers driven by micro actuators. Because of these promising advantages, the
      WSSD has prospects of wide range of applications, such as in laser projection
      displays.

PMID- 30119340
TI  - Polarization-dependent liquid crystalline polymeric lens array with aberration
      improved aspherical curvature for low 3D crosstalk in 2D/3D switchable mobile
      multi-view display.
AB  - We demonstrated a 2D/3D switchable mobile display using a polarization-dependent
      switching liquid crystalline polymeric (LCP) lens array film. In spite of short
      viewing distance and enough viewing window conditions provided by a small f
      number lens for mobile displays, the 3D images when switched to the multi-view 3D
      mode showed a low crosstalk property owing to the improved lens aberration, as
      applying an aspherical lens curvature interface between the planar-convex LCP
      layer and the concave-planar isotropic polymer layer. Both 2D and 3D images were
      demonstrated based on a 5.5-inch quad high definition mobile display panel, where
      the binocular crosstalk of the 3D mode was 3.3%.

PMID- 30119341
TI  - Nonlinear refractive index of electric field aligned gold nanorods suspended in
      index matching oil measured with a Hartmann-Shack wavefront aberrometer.
AB  - The capability to dynamically control the nonlinear refractive index of plasmonic
      suspensions may enable innovative nonlinear sensing and signaling
      nanotechnologies. Here, we experimentally determine the effective nonlinear
      refractive index for gold nanorods suspended in an index matching oil aligned
      using electric fields, demonstrating an approach to modulate the nonlinear
      optical properties of the suspension. The nonlinear optical experiments were
      carried out using a Hartmann-Shack wavefront aberrometer in a collimated beam
      configuration with a high repetition rate femtosecond laser. The suspensions were
      probed at 800 nm, overlapping with the long-axis absorption peak of the nanorods.
      We find that the effective nonlinear refractive index of the gold nanorods
      suspension depends linearly on the orientational order parameter, S, which can be
      understood by a thermally induced nonlinear response. We also show the magnitude
      of the nonlinear response can be varied by ~ 60%.

PMID- 30119342
TI  - Variable optical null based on a yawing CGH for measuring steep acylindrical
      surface.
AB  - Measurement of steep acylindrical surface has the difficulty with respect to its
      large localized slope, which may lead to irresolvable fringe densities in off
      axis subapertures. To address this problem, we analyze the departure of off-axis
      acylindrical subapertures, and propose a measurement strategy by yawing the
      cylinder null. When the cylinder null is yawed with different angles, variable
      mounts of acylindrical wavefronts are generated to compensate most of the
      aberrations for different off-axis subapertures. Thus, the fringe densities are
      drastically reduced within the vertical dynamic range of interferometers. To
      connect all subaperture together, we also propose an acylindrical stitching
      approach. Experimental results demonstrate that an acylindrical lens with a
      departure of up to 81um from the best-fitting cylinder can be measured using the
      proposed method. More importantly, it does not require an additional
      reconfigurable optical null, making the measurement system simple and
      inexpensive.

PMID- 30119343
TI  - Elucidating uranium monoxide spectral features from a laser-produced plasma.
AB  - Uranium, because of its pyrophoricity, oxidizes rapidly in an oxygen-containing
      high-temperature environment. However, so far, the identification of uranium
      oxide (UO) emission from a laser-produced plasma system is limited to a spectral
      feature around 593.55 nm. The aim of this study is to elucidate UO emission
      features in the visible spectral regime from uranium plasmas generated in an
      environment with varying oxygen concentrations. The plasmas are produced by
      focusing nanosecond laser pulses on a uranium metal target in a controlled
      ambient environment. Space- and time-resolved optical emission spectroscopic
      investigations are used for isolating UO molecular emission structures from
      crowded U atomic line emission. Our studies highlight that the emission from a U
      plasma, even in the presence of trace oxygen is accompanied by a strong
      background-like emission with partially resolved bands from uranium monoxide and
      higher oxides. We also report several UO spectral emission bands in the visible
      spectral region.

PMID- 30119344
TI  - All-dielectric transformation medium mimicking a broadband converging lens.
AB  - Radio waves carrying orbital angular momentum (OAM) may potentially increase
      spectrum efficiency and channel capacity based on their extra rotational degree
      of freedom. However, due to their divergence characteristics, vortex waves are
      not suitable to transmit over a long distance in the radio frequency (RF) and
      microwave domains. In this paper, a transformation optics (TO) based all
      dielectric converging lens is proposed. The beam divergence angle of the vortex
      wave passing through the lens can be decreased from 25 degrees  to 9 degrees .
      The transformed material parameters of the converging lens are determined by
      solving Laplace's equation subject to specific boundary conditions. Far-field
      antenna radiation patterns as well as near-field helical phase and electric field
      amplitude distributions obtained from numerical simulations are reported,
      demonstrating the broadband characteristics of the proposed microwave lens.
      Moreover, the all-dielectric compact lens design comprised by a graded
      permittivity profile can be fabricated by additive manufacturing technology,
      which greatly facilitates the potential development and application of vortex
      wave based wireless communications.

PMID- 30119345
TI  - High sampling rate single-pixel digital holography system employing a DMD and
      phase-encoded patterns.
AB  - A single-pixel digital holography system with phase-encoded illumination using a
      digital micromirror device (DMD) as a spatial light modulator (SLM) is presented.
      The enhanced switching rate of DMDs, far exceeding the stringent frame-rate of
      liquid crystal SLMs, allows recording and reconstruction of complex amplitude
      distributions in just a few seconds. A single amplitude binary modulation device
      is used for concurrently displaying the phase-encoded sampling patterns,
      compensating the distortion of the wavefront, and applying phase-shifting, by
      means of computer generated holograms. Our detection system consists of a simple
      photodiode that sequentially records the irradiance fluctuations corresponding to
      the interference between object and reference beams. The system recovers phase
      and amplitude information even when a diffuser is placed in front of the
      photodiode.

PMID- 30119346
TI  - Defocusing parameter selection strategies based on PSF measurement for square
      binary defocusing fringe projection profilometry.
AB  - Three-dimensional (3D) shape measurement system with binary defocusing technique
      can perform high-speed and flexible measurements if binary fringe patterns are
      defocused by projector properly. However, the actual defocusing degree is
      difficult to set, and the fringe period is difficult to determine accordingly. In
      this study, we present a square-binary defocusing parameter selection framework.
      First, we analyze the fringe formation process mathematically. The defocusing
      degree is quantified and manipulated by using the focusing distance of projector,
      which is calibrated by point spread function measurement. To optimize parameter
      selection, single-point sinusoidal error is modeled as the objective function for
      the evaluation of the defocusing effect. We verify the correctness by using
      different parameter combinations and object measurements in our experiments. The
      appropriate defocusing parameters can be easily obtained according to the
      analysis of practical system setup, which improves the quality and robustness of
      the system.

PMID- 30119347
TI  - Geometric frustration in a hexagonal lattice of plasmonic nanoelements.
AB  - We introduce the concept of geometric frustration in plasmonic arrays of
      nanoelements. In particular, we present the case of a hexagonal lattice of Au
      nanoasterisks arranged so that the gaps between neighboring elements are small
      and lead to a strong near-field dipolar coupling. Besides, far-field interactions
      yield higher-order collective modes around the visible region that follow the
      translational symmetry of the lattice. However, dipolar excitations of the gaps
      in the hexagonal array are geometrically frustrated for interactions beyond
      nearest neighbors, yielding the destabilization of the low energy modes in the
      near infrared. This in turn results in a slow dynamics of the optical response
      and a complex interplay between localized and collective modes, a behavior that
      shares features with geometrically frustrated magnetic systems.

PMID- 30119348
TI  - Bayes' theorem-based binary algorithm for fast reference-less calibration of a
      multimode fiber.
AB  - In this paper, we present a Bayes' theorem-based high-speed algorithm, to measure
      the binary transmission matrix of a multimode fiber using a digital micromirror
      device, in a reference-less multimode fiber imaging system. Based on conditional
      probability, we define a preset threshold to locate those digital-micromirror
      device pixels that can be switched 'ON' to form a focused spot at the output.
      This leads to a binary transmission matrix consisting of '0' and '1' elements.
      High-enhancement-factor light focusing and raster-scanning at the distal end of
      the fiber are demonstrated experimentally. The key advantage of our algorithm is
      its capability for fast calibration of a MMF to form a tightly focused spot. In
      our experiment, for 5000 input-output pairs, we only need 0.26 s to calibrate one
      row of the transmission matrix to achieve a focused spot with an enhancement
      factor of 28. This is more than 10 times faster than the prVBEM algorithm. The
      proposed Bayes' theorem-based binary algorithm can be applied not only in
      multimode optical fiber focusing but also to other disordered media.
      Particularly, it will be valuable in fast multimode fiber calibration for
      endoscopic imaging.

PMID- 30119349
TI  - On-chip quantum interference with heralded photons from two independent micro
      ring resonator sources in silicon photonics.
AB  - High visibility on-chip quantum interference among indistinguishable single
      photons from multiples sources is a key prerequisite for integrated linear
      optical quantum computing. Resonant enhancement in micro-ring resonators
      naturally enables brighter, purer and more indistinguishable single-photon
      production without any tight spectral filtering. The indistinguisha-bility of
      heralded single-photons from multiple micro-ring resonators has not been measured
      in any photonic platform. Here, we report on-chip indistinguishability
      measurements of heralded single-photons generated from independent micro-ring
      resonators by using an on-chip Mach-Zehnder interferometer and spectral
      demultiplexer. We measured the raw heralded two-photon interference fringe
      visibility as 72 +/- 3%. This result agrees with our model, which includes device
      imperfections, spectral impurity and multi-pair emissions. We identify multi-pair
      emissions as the main factor limiting the nonclassical interference visibility,
      and show a route towards achieving near unity visibility in future experiments.

PMID- 30119350
TI  - Ptychographical intensity interferometry imaging with incoherent light.
AB  - Intensity interferometry (II), the landmark of the second-order correlation,
      enables very long baseline observations at optical wavelengths, providing imaging
      with microarcsecond resolution. However, the unreliability of traditional phase
      retrieval algorithms required to reconstruct images in II has hindered its
      development. We here develop a method that circumvents this challenge, which
      enables II to reliably image complex shaped objects. Instead of measuring the
      whole object, we measure it part by part with a probe moving in a ptychographic
      way: adjacent parts overlap with each other. A relevant algorithm is developed to
      reliably and rapidly recover the object in a few iterations. Moreover, we propose
      an approach to remove the requirement for a precise knowledge of the probe,
      providing an error-tolerance of more than 50% for the location of the probe in
      our experiments. Furthermore, we extend II to short distance scenarios, providing
      a lensless imaging method with incoherent light and paving a way towards
      applications in X-ray imaging.

PMID- 30119351
TI  - Secret key rates for intensity-modulated dual-threshold detection key
      distribution under individual beam splitting attacks.
AB  - We investigate the secret key rates for the recently proposed intensity-modulated
      dual-threshold key distribution [T. Ikuta and K. Inoue, New J. Phys. 18 (2016)]
      under beam splitting attacks. We show that previous assumptions on an
      eavesdropper that performs hard decision measurements on the channel,
      overestimates the secret key rate. We discuss the impact of an eavesdropper that
      can measure full soft information and give the secret key rates under forward and
      reverse reconciliation. Further, we perform simulations for different system
      assumptions and show the optimal modulation depths for these systems. We also
      outline an attack on this protocol based on photon counting that prohibits secret
      key generation.

PMID- 30119352
TI  - Laser speckle formed disordered micro-meander structures for light extraction
      enhancement of flexible organic light-emitting diodes.
AB  - A new approach for efficiently recovering the wasted light energy in conventional
      flexible organic light-emitting diodes (FOLEDs) is developed by implementing
      disordered micro-meander structures (DMMs) via laser speckle holography
      technology. Compared to conventional flat device architecture, the structured
      FOLEDs with DMMs result in substantial improvement of the device efficiency and
      superior angular color stability. The resulting current efficiency (CE) and
      external quantum efficiency (EQE) are 1.31 and 1.39 times that of a common flat
      structure, respectively. Moreover, the proposed DMMs micro-structure
      simultaneously offers the unique characteristics of angular color stability with
      a wide viewing angle, which is usually considered as the criteria of the high
      quality lighting applications. We hope that the demonstrated method could provide
      an alternative way for the development of high efficiency flexible OLEDs.

PMID- 30119353
TI  - Impact of gamma-ray radiation-induced photodarkening on mode instability
      degradation of an ytterbium-doped fiber amplifier.
AB  - The laser performance of a high-power ytterbium-doped fiber amplifier is mainly
      hindered by the onset of mode instability. In this work, the slope efficiency and
      mode instability threshold of the ytterbium-doped fiber under various gamma-ray
      radiation doses have been measured. Experimental results reveal that gamma-ray
      radiation-induced photodarkening degrades mode instability severely, and gamma
      ray radiation-induced mode instability degradation can be partly bleached by
      hours of pump-light injection. It is shown that gamma-ray radiation-induced
      photodarkening results in a steep reduction of slope efficiency and mode
      instability threshold; moreover, the entire irradiated fiber can be partly
      bleached by hours of pump-light injection and exhibits both time and gamma-ray
      radiation-dose saturation properties. The experimental results indicate that mode
      instability mitigation can be partly realized by pump-light injection and implies
      photodarkening suppression is beneficial for TMI mitigation, which is very
      promising for the advancement of high-power fiber lasers.

PMID- 30119354
TI  - Experimental observation of three-photon interference between a two-photon state
      and a weak coherent state on a beam splitter.
AB  - We experimentally demonstrated a three-photon interference on a beam splitter
      between a weak coherent state and a two-photon state produced by a spontaneous
      parametric down conversion. It indicates that a combined three-photon probability
      amplitude, which is formed by the two-photon state and one-photon from the
      coherent state, can be used to interfere with another three-photon probability
      amplitude from the coherent state. The observed three-photon coincidence rate
      showed that the interference depended on not only the relative phase between the
      two interference field but also the amplitude of the weak coherent state. This
      may introduce another free parameter for preparing quantum state, such as high
      N00N state, with quantum interference.

PMID- 30119356
TI  - Generation of multiqubit steady-state quantum correlation by squeezed-reservoir
      engineering.
AB  - Stationary quantum correlation among two-level systems (TLSs) in steady state is
      one of unique resources for applications in quantum information processing. Here
      we propose a scheme to generate such quantum correlation among the TLSs inside a
      lossy cavity. It is found that, by applying a broadband squeezed laser acting as
      a squeezed-vacuum reservoir to the cavity, a stable quantum correlation of the
      TLSs can be generated. By adiabatically eliminating the cavity field, we derive a
      reduced master equation of the TLSs in the bad-cavity limit. We show that the
      generated quantum correlation is essentially determined by the squeezing features
      transferred from the squeezed-vacuum reservoir via the cavity field as a quantum
      bus. We study the effect of the system parameters, such as the squeezing, the
      detuning, the coupling strength, and the decay rate of the TLSs, on the
      performance of the scheme. The feasibility of our proposal is supported by the
      application of currently available experimental techniques.

PMID- 30119355
TI  - Wideband and continuously-tunable fractional photonic Hilbert transformer based
      on a single high-birefringence planar Bragg grating.
AB  - We propose and experimentally demonstrate wideband and continuously tunable
      fractional-order photonic Hilbert transformers (FrHT). These are realized by a
      single apodized planar Bragg grating within a high-birefringence planar
      substrate. The fractional order of the FrHT is continuously tuned and precisely
      controlled by changing the polarization state of the input light. The
      experimental characterization demonstrates an operating bandwidth up to 120 GHz
      with amplitude ripples below 3 dB. The optical phase shift response is directly
      measured to verify the proposed tuning property, demonstrating transform orders
      of around 1, 0.7, and 0.5. This approach is simple, stable, and compact compared
      to other existing methods and has great potential in the fields of ultrafast all
      optical signal processing.

PMID- 30119357
TI  - Metamaterial perfect absorber with unabated size-independent absorption.
AB  - Metamaterial absorbers open a new door for the design of optical harvesting
      devices ranging from the microwave to optical regimes. The top resonator in these
      structures is critical for the function of metamaterial absorbers. The resonant
      frequency, bandwidth, and maximum absorption mainly depend on the choice of
      material, shape, and size of the top resonator. The maximum absorption is
      generally impaired as the size of the resonator changes, due to the high
      sensitivity of impedance matching with the medium. In this paper, we
      experimentally demonstrate a metamaterial perfect absorber with unabated
      absorption as its resonator's size changes. The perfect absorber is based on an
      array of metal squares inscribed with a hollow square. The absorption maxima stay
      above 98% as the size changes from 600 to 1500 nm in the mid-infrared region,
      agreeing with simulated results yielding an absorption of ~100%. The unabated
      absorption properties can be interpreted by the equivalent circuit theory.
      Moreover, the experimental absorption remains above 91% for incident angles
      change up to 50 degrees , both for TE and TM polarization. Our work offers a
      method for achieving stable perfect absorption in sensing, filtering, and
      selective thermal emission.

PMID- 30119358
TI  - Characterization and generation of high-power multi-axis vortex beams by using
      off-axis pumped degenerate cavities with external astigmatic mode converter.
AB  - The generalized geometric mode with several high-order Hermite-Gaussian (HG)
      beams localized on ray periodic orbits in the degenerate resonator is generated
      by an off-axis pumped Nd:YVO4 laser, by performing beam transformation via an
      astigmatic mode converter, the generalized geometric modes are found that can be
      converted into the multi-axis vortex beams with the bundled-rings structures.
      Experimental results reveal that the generated multi-axis vortex beams can
      preserve quite stable beam structures even under high-power operation. Moreover,
      the radius of the bundled rings for the multi-axis vortex beams can be flexibly
      adjusted by the off-axis pumping to lead to vortex structures with easily
      controlled orbital angular momentum distribution. The good agreement between the
      experimental and theoretical results of propagation evolution for the astigmatic
      transformation of generalized geometric modes further verify the feasibility of
      using the proposed system to realize various high-powered, multi-center vortex
      beams with good reliability and predictability.

PMID- 30119359
TI  - Direct characterization of the evanescent field in objective-type total internal
      reflection fluorescence microscopy.
AB  - Total internal reflection fluorescence (TIRF) microscopy is a commonly used
      method for studying fluorescently labeled molecules in close proximity to a
      surface. Usually, the TIRF axial excitation profile is assumed to be single
      exponential with a characteristic penetration depth, governed by the incident
      angle of the excitation laser beam towards the optical axis. However, in
      practice, the excitation profile does not only comprise the theoretically
      predicted single-exponential evanescent field, but also an additional non
      evanescent contribution, supposedly caused by scattering within the optical path
      or optical aberrations. We developed a calibration slide to directly characterize
      the TIRF excitation field. Our slide features ten height steps ranging from 25 to
      550 nanometers, fabricated from a polymer with a refractive index matching that
      of water. Fluorophores in aqueous solution above the polymer step layers sample
      the excitation profile at different heights. The obtained excitation profiles
      confirm the theoretically predicted exponential decay over increasing step
      heights as well as the presence of a non-evanescent contribution.

PMID- 30119360
TI  - Transmission of wireless signals using space division multiplexing in few mode
      fibers.
AB  - Evolution of next generation wireless networks brings challenges to efficiently
      transmit a large amount of data from a base station to a remote antenna unit. We
      investigate a space division multiplexing technique that employs few mode fibers
      (FMFs) to transmit 3 * 3 MIMO wireless signals, aiming to employ a common digital
      signal processing (DSP) unit to equalize both the fiber and wireless channel. We
      optimize system parameters and obtain above 28 dB and 23 dB signal-to
      interference and noise ratio (SINR) for 3 meters wireless systems with 500 m and
      2 km FMF, which correspond to the transmission capacity of 578 Mb/s and 468 Mb/s
      using a 20 MHz bandwidth, respectively. Moreover, we analyze that the nonlinear
      spectrum distortion due to the combined effect of nonlinearity in the directly
      modulated laser and the differential mode delay in multimode fibers and validate
      it by simulations.

PMID- 30119361
TI  - On the recovery conditions for practical ghost imaging with AMP algorithm.
AB  - The approximate message passing algorithm (AMP) is introduced for practical ghost
      imaging (GI). This paper proposes to use preconditioning to modified the sensing
      matrix such that it satisfies the assumptions of the original AMP algorithm.
      Furthermore, this paper points out that the speckles used in practical GI system
      are spatially correlated, and this will degrade the imaging performance. The
      parameter estimations of exponential power distribution reveal that the rows of
      modified sensing matrix are indeed bounded by the Laplace distribution, which is
      heavy-tailed. Then, the recovery conditions for such sensing matrix are
      investigated. Finally, the semi-real experiments and real data processing have
      validated the proposed imaging method and shown that the required number of
      measurements for correlated speckles are significantly greater than independent
      and identically distributed (i.i.d.) measurement. The results of this paper can
      be used to guide the design of practical GI remote sensing systems.

PMID- 30119362
TI  - Prism-hologram-prism sandwiched recording method for polarization-selective
      substrate-mode volume holograms with a large diffraction angle.
AB  - We propose a prism-hologram-prism sandwiched recording method for the fabrication
      of polarization-selective substrate-mode volume holograms with a large
      diffraction angle. In fabrication, the C-RT20 photopolymer is sandwiched between
      two 45 degrees -90 degrees -45 degrees  prisms and the interference fringes can
      be easily recorded in the recording material. The experimental results are in
      good agreement with the theoretical predictions. The proposed method features of
      a reflection-type recording setup for a transmission element and belongs to a
      technique of longer-wavelength construction for shorter-wavelength
      reconstruction. In addition, the method is much easier than the traditional
      recording method of two incident beam interference and has application potential
      in holographic photonics.

PMID- 30119363
TI  - Parallel radio-frequency signal-processing unit based on mode multiplexed
      photonic integrated circuit.
AB  - We propose and demonstrate a monolithically integrated mode division multiplexing
      (MDM) photonic system for parallel radio-frequency (RF) signal processing using a
      silicon platform. Two independent lowpass integrated microwave photonic filters
      (IMPFs) are successfully demonstrated using the proposed scheme. Full integration
      of active and passive devices ensures small footprint and good performance for
      microwave photonic applications. The adoption of MDM extends the parallel
      processing capability of a single wavelength line. The first order transverse
      electric (TE1) and second order transverse electric (TE2) modes are utilized for
      two IMPFs, with minimum bandwidth 3.7 and 3.8 GHz, respectively. Furthermore, by
      elaborately controlling the micro-ring based mode convertors, the continuous
      tuning of bandwidth is achieved from 3.7 to 8 GHz for TE1 and 3.8 to 7.6 GHz for
      TE2 based IMPFs.

PMID- 30119364
TI  - Optical lattices and optical vortex arrays in clustered speckles.
AB  - Clustered speckle, optical lattices, and their optical vortex array are subjects
      of interest in optical wave manipulation. In this study, disordered optical
      lattices and vortex arrays with different unit structures were found in the
      clustered speckles generated by a circularly-distributed multi-pinhole scattering
      screen when it was illuminated by coherent light. These structures included
      hexagonal lattices, kagome lattices, and honeycomb lattices. Moreover, optical
      lattices with asymmetric units generated by modulation of phases with non-integer
      multiples of 2pi were discussed. Theoretical analysis and numerical calculations
      demonstrated that optical lattices in clustered speckles in the observation plane
      were generated by the phase modulations of the random scattering screen. The
      lattice type depended on the number of 2pi multiples of the summed phase
      difference between the pinholes. Additionally, the conditions for the formation
      of periodical optical lattices and their vortex arrays were given. Different
      optical lattices and their vortex arrays appearing simultaneously in the
      clustered speckle were difficult to generate using the common multi-beam
      interference system. This phenomenon is of great significance in the study of the
      orbital angular momentum of photons and other fields.

PMID- 30119365
TI  - Long-range Raman distributed temperature sensor with high spatial and temperature
      resolution using graded-index few-mode fiber.
AB  - We designed and fabricated a graded-index few-mode fiber (GI-FMF) with large
      effective mode area and low intermodal dispersion for Raman distributed
      temperature sensor (RDTS) to simultaneously achieve high spatial and temperature
      resolution over long distance. In experiment, we measured the spatial and
      temperature resolution of the RDTS using different types of fibers under
      different launch conditions based on a commercially available RDTS system. By
      using the GI-FMF under the overfilled launch condition, we achieved a 1  degrees
      C temperature resolution with a spatial resolution of 1.13 m at the distance of
      25 km. The spatial resolution using the standard MMF degraded to 2.58 m with only
      a 0.3  degrees C higher temperature resolution in comparison. As a result, the GI
      FMF under the few-mode operation condition can provide a desirable temperature
      resolution comparable with that of the MMF with a negligible degradation on
      spatial resolution. Moreover, the RDTS using the GI-FMF under the quasi-single
      mode operation condition achieved a temperature resolution of 4.7  degrees C at
      the distance of 25 km with a 2.2  degrees C improvement and no degradation on
      spatial resolution compared with that using the standard SMF.

PMID- 30119366
TI  - Simplified chirp characterization in single-shot supercontinuum spectral
      interferometry.
AB  - Single-shot supercontinuum spectral interferometry (SSSI) is an optical technique
      that can measure ultrafast transients in the complex index of refraction. This
      method uses chirped supercontinuum reference/probe pulses that need to be pre
      characterized prior to use. Conventionally, the spectral phase (or chirp) of
      those pulses can be determined from a series of phase or spectral measurements
      taken at various time delays with respect to a pump-induced modulation. Here we
      propose a novel method to simplify this process and characterize reference/probe
      pulses up to the third order dispersion from a minimum of 2 snapshots taken at
      different pump-probe delays. Alternatively, without any pre-characterization, our
      method can retrieve both unperturbed and perturbed reference/probe phases,
      including the pump-induced modulation, from 2 time-delayed snapshots. From
      numerical simulations, we show that our retrieval algorithm is robust and can
      achieve high accuracy even with 2 snapshots. Without any apparatus modification,
      our method can be easily applied to any experiment that uses SSSI.

PMID- 30119367
TI  - Crystallization control toward colorless cerium-doped scintillating glass.
AB  - The construction of cerium-doped materials is of great technological importance
      for various applications, including smart lighting, biological shielding and high
      energy ray and particle detection. A major challenge is the efficient prevention
      of the undesired colorization after cerium doping. Here we present the
      nanocrystallization method for constructing colorless cerium-doped glass with
      extremely high cerium concentration (15 mol%). The structure and optical
      characterizations confirm that the notable color change of glass is associated
      with the precipitation of CeF3 crystalline phase during heat-treatment. The
      chemical state investigation shows that most of cerium ions exist in the form of
      Ce3+ in both the glass and glass-ceramic samples. The chemical environment study
      indicates a dramatic change in the local structure unit from -Ce-O- to -Ce-F-,
      which is believed to dominate the decoloring phenomenon in cerium doped glass. As
      a result, a significant improvement in the ultraviolet excited luminescence (~35
      times enhancement in intensity) and scintillating performance can be achieved,
      pointing to potential applications in X-ray detection.

PMID- 30119368
TI  - Material features based compensation technique for the temperature effects in a
      polymer diaphragm-based FBG pressure sensor.
AB  - Fiber Bragg grating (FBG) based sensors have been applied to measure several
      parameters, such as pressure, vibration, liquid level, humidity, the
      concentration of chemical compounds, among others. An approach to measure
      parameters like liquid level, pressure and vibration are to embed the FBG on a
      diaphragm, which is generally made of a polymeric material. Nevertheless, the
      mechanical properties of polymers depend on temperature variation. For this
      reason, a polymer diaphragm can enhance the cross-sensitivity between the strain
      and temperature on an FBG sensor. In order to overcome this limitation, this
      paper presents a compensation technique for the temperature effects on an oblong
      polymer diaphragm-based FBG pressure sensor. The presented technique is based on
      the analytical model of the sensor, which takes into account the variation of the
      diaphragm properties with temperature obtained through a dynamic mechanical
      analysis of the diaphragm material. Results show that the developed technique
      reduces the sensor cross-sensitivity to about 1.74 Pa/ degrees C. Furthermore,
      the presented technique is compared with the direct difference between the FBG
      strain and temperature responses presented in reference works. The comparison
      shows a better performance of the technique presented in this paper with respect
      to the cross-sensitivity and the root mean squared error.

PMID- 30119369
TI  - Flexible generation of 28 Gbps PAM4 60 GHz/80 GHz radio over fiber signal by
      injection locking of direct multilevel modulated laser to spacing-tunable two
      tone light.
AB  - To meet the ever-increasing bandwidth demands in the future broadband wireless
      networks, the millimeter-wave (mm-wave) frequency region is being actively
      perused, owing to its broad bandwidth and high frequencies. In this paper, a
      photonic mm-wave system is proposed and experimentally demonstrated based on the
      injection locking of a direct multilevel modulated laser to a spacing-tunable two
      tone light. Since the mm-wave frequency of the generated signal is locked to the
      frequency spacing of the injected two-tone light, it shows better frequency
      stabilization than the schemes based on two free-running lasers. Moreover, by
      simply tuning the tone spacing, the mm-wave frequency could be easily re
      configured, offering flexibility in the mm-wave signal generation. Instead of
      using complex and expensive optical modulators, the multilevel modulation on the
      mm-wave data carrier is implemented through the direct multilevel modulation of a
      laser and the injection locking. A 28 Gbps four-level pulse amplitude modulation
      (PAM4) is realized by biasing a 10 G-class laser at a current far from the
      threshold, providing a cost-effective and simple mm-wave generation scheme. In
      the experiment, a photonic approach to generating 28 Gbps PAM4 60 GHz/80 GHz mm
      wave signals is experimentally demonstrated. A power penalty of less than 0.2 dB
      is observed for the filtered-out PAM4 signals with respect to the original PAM4.
      Besides, an ultra-low phase noise of up to -98 dBc/Hz is obtained for the mm-wave
      carriers after the injection locking. The proposed scheme possesses the
      flexibility and frequency stability of the mm-wave frequency, and also has low
      cost and implementation complexity.

PMID- 30119370
TI  - Low repetition rate 343 nm passively Q-switched solid-state laser for time
      resolved fluorescence spectroscopy.
AB  - We demonstrate a low-cost 343 nm solid-state laser delivering up to 20 uJ per
      pulse, with a pulse width of 2.3 ns at a repetition rate of 100 Hz. The 343 nm is
      obtained through a third harmonic generation of a passively Q-switched 1030 nm
      Yb:YAG laser with pulse energy of 190 uJ at 100 Hz and a pulse width of 5.4 ns.
      The IR-UV conversion efficiency is 10.4%, comparable to that achieved with mode
      locked IR lasers. The light source is electronically controlled for easy
      synchronization with a detection circuit. The low repetition rate specifically
      targets applications exploiting the millisecond scale lifetime of lanthanides
      employed in fluoroimmunoassay measurements for time-resolved fluorescence
      spectroscopy. Low repetition rate and even pulse-on-demand operation is
      demonstrated.

PMID- 30119371
TI  - Timing and probability of crosstalk in a dense CMOS SPAD array in pulsed TOF
      applications.
AB  - As the distance between neighboring devices in large CMOS single-photon avalanche
      diode (SPAD) arrays is reduced for improving the density, increased crosstalk
      becomes an important issue, limiting the maximum practical fill factor of the
      array. In this study, the temporal correlation of crosstalk events, as well as
      the crosstalk probability, and their dependence on parameters, such as the
      illumination wavelength and intensity, and the distance between SPADs, are
      investigated via measurement of a ~45%-fill factor CMOS SPAD array fabricated
      using 0.35-um high-voltage CMOS technology. The SPADs have 24 um * 24 um square
      shaped active areas, and all devices share a common deep-N-well cathode. On-chip
      time-to-digital converters with 65-ps resolution are used to measure the timing
      of crosstalk events in "coincidence measurements." For the crosstalk
      measurements, the internal noise in one SPAD is used to produce crosstalk events
      in the neighboring devices. The measurement results indicate both optical and
      electrical crosstalk with the crosstalk events, having a specific temporal
      distribution. The crosstalk probability in the first two adjacent pixels is found
      to be 0.3% and 0.01%, with a distribution having full widths at half maximum
      (FWHMs) of 700 and 400 ps, respectively. In pulsed time-of-flight measurements,
      when one SPAD is triggered with external short-pulsed (FWHM of approximately 200
      ps) illumination, extra correlated noise in the adjacent SPADs added to the
      crosstalk noise, increasing the correlated noise considerably. This additional
      noise was a secondary effect of the absorbed laser photons deep in the substrate.

PMID- 30119373
TI  - High stability luminophores: fluorescent CsPbX3 (X = Cl, Br and I) nanofiber
      prepared by one-step electrospinning method.
AB  - The novel fluorescent nanofiber membranes of CsPbX3 (FNMs/CPX, X = Cl, Br, I)
      with a wide photoluminescence range from 405 nm to 675 nm are fabricated by a one
      step electrospinning method in this paper. Owing to the polymer cladding, these
      FNMs/CPX show much better thermal and humid stability compared to the common
      CsPbX3 particles, and the corresponding white light-emitting diode prepared by
      them also exhibits excellent optical properties. Without adopting any complicated
      processes, this method opens up a brand new way for the perovskite materials
      using in lighting and display fields.

PMID- 30119372
TI  - Broadband calibration-free cavity-enhanced complex refractive index spectroscopy
      using a frequency comb.
AB  - We present broadband cavity-enhanced complex refractive index spectroscopy (CE
      CRIS), a technique for calibration-free determination of the complex refractive
      index of entire molecular bands via direct measurement of transmission modes of a
      Fabry-Perot cavity filled with the sample. The measurement of the cavity
      transmission spectrum is done using an optical frequency comb and a mechanical
      Fourier transform spectrometer with sub-nominal resolution. Molecular absorption
      and dispersion spectra (corresponding to the imaginary and real parts of the
      refractive index) are obtained from the cavity mode broadening and shift
      retrieved from fits of Lorentzian profiles to the individual cavity modes. This
      method is calibration-free because the mode broadening and shift are independent
      of the cavity parameters such as the length and mirror reflectivity. In this
      first demonstration of broadband CE-CRIS we measure simultaneously the absorption
      and dispersion spectra of three combination bands of CO2 in the range between
      1525 nm and 1620 nm and achieve good agreement with theoretical models. This
      opens up for precision spectroscopy of the complex refractive index of several
      molecular bands simultaneously.

PMID- 30119374
TI  - Automated distinction of shearing and distortion artefacts in structured
      illumination microscopy.
AB  - Any motion during an image acquisition leads to an artefact in the final image.
      Structured illumination microscopy (SIM) combines several raw images into one
      high-resolution image and is thus particularly prone to these motion artefacts.
      Their unpredictable shape cannot easily be distinguished from real high
      resolution content. We previously implemented a motion detection specifically for
      SIM, which had two shortcomings which are solved here. First, the brightness
      dependency of the motion signal is removed. Second, the empirical threshold of
      the calculated motion signal was not a threshold at a maximum allowed artefact.
      Here we investigate which artefacts are still acceptable and which linear
      movement creates them. Thus, the motion signal is linked with the maximal
      strength of the expected artefact. A signal-to-noise analysis including
      classification successfully distinguishes between artefact-free imaging, shearing
      and distortion artefacts in biological specimens. A shearing, as in wide-field
      microscopy, is the dominant reconstruction artefact, while distortions arise not
      until surprisingly fast movements.

PMID- 30119375
TI  - Surface lattice resonances based on parallel coupling in metal-insulator-metal
      stacks.
AB  - Narrowband emitters or absorbers based on LSPRs (Localized Surface Plasmon
      Resonances) in MIM structures have drawn increasing attention because of their
      filter-free character, small volume and low power consumption. However, the
      plasmonics community has slowly come to the consensus that the ohmic losses of
      the metals are simply too high to realize ultra-narrowband resonance. Recently,
      parallel coupling between the LSPR and the lattice diffraction has also been
      present in the metallic particle array, which shows greater tolerance to
      inhomogeneous environment and has greater potential in the far field emission
      applications. In this paper, the delocalized parallel coupling with ultra
      narrowband is stimulated in the Coating-MIM structure, at mid-infrared. Besides,
      coating with hundreds of nanometers is employed to modulate the coupled
      efficiency. By inducing this ultra-narrowband resonance, MIM structures may
      extend their application area into ultra-high performance.

PMID- 30119376
TI  - Ka-band microwave photonic ultra-wideband imaging radar for capturing
      quantitative target information.
AB  - Extracting precise target characteristics from microwave image is needed and
      calls for high-resolution microwave imaging radar systems. In this paper, a Ka
      band ultra-wideband microwave photonic (MWP) imaging radar is developed and
      experimentally demonstrated. In the transmitter, continuous ultra-wideband linear
      frequency modulation (LFM) wave is generated based on optical frequency
      sextupling technique. In the receiver, a combination of optical frequency mixer
      with fiber delay lines and electric analog-to-digital converter (ADC) is capable
      of receiving target echoes and imaging targets with different distances. The
      maximum instantaneous bandwidth of the transmitted waveform is measured to be
      10.02 GHz and corresponding range resolution is calibrated to be 1.68 cm. Out
      field tests with demonstrator working at synthetic aperture radar (SAR) or
      inverse synthetic aperture radar (ISAR) mode are carried out. Different targets
      such as an unmanned aerial vehicle (UAV), airliner and Leifeng pagoda are imaged.
      Based on corresponding high-resolution microwave images, quantitative information
      of the targets can be identified, which shows the great potential of the radar
      demonstrator for various remote sensing applications.

PMID- 30119377
TI  - Probing the origin of highly-efficient third-harmonic generation in plasmonic
      nanogaps.
AB  - Plasmonic structures can precisely localize electromagnetic energy to deep
      subwavelength regions resulting in significant field enhancement useful for
      efficient on-chip nonlinear generation. However, the origin of large nonlinear
      enhancements observed in plasmonic nanogap structures consisting of both
      dielectrics and metals is not fully understood. For the first time, here we probe
      the third harmonic generation (THG) from a variety of dielectric materials
      embedded in a nanogap plasmonic cavity. From comprehensive spectral analysis of
      the THG signal, we conclude that the nonlinear response results primarily from
      the dielectric spacer layer itself as opposed to the surrounding metal. We
      achieved a maximum enhancement factor of more than six orders of magnitude
      compared to a bare gold film, which represents a nonlinear conversion efficiency
      of 8.78 * 10-4%. We expect this new insight into the nonlinear response in
      ultrathin gaps between metals to be promising for on-chip nonlinear devices such
      as ultrafast optical switching and entangled photon sources.

PMID- 30119378
TI  - Laser direct writing of graphene nanostructures beyond the diffraction limit by
      graphene oxidation.
AB  - The fabrication ability of graphene nanostructures is the cornerstone of graphene
      based devices, which are of particular interest because of their broad optical
      response and gate-tunable properties. Here, via laser-induced redox reaction of
      graphene and silica, we fabricate nano-scale graphene structures by femtosecond
      laser direct writing. The resolution of destructed graphene lines is far beyond
      the diffraction limit up to 100 nm with a precision as small as +/- 7 nm.
      Consequently, graphene nanostructures are fabricated precisely and excellent
      plasmon responses are detected. This novel fabrication method of graphene
      nanostructures has the advantages of low costs, high efficiency, maskless and
      especially high precision, which would pave the way for practical application of
      graphene-based optical and electronic devices.

PMID- 30119379
TI  - Temporal radio-frequency spectrum analyzer, based on asynchronous optical
      sampling assisted temporal convolution.
AB  - We propose and experimentally demonstrated an all-optical radio-frequency (RF)
      spectrum analyzer, based on asynchronous optical sampling (ASOPS) assisted
      temporal convolution. The RF spectrum is mapped onto the time axis with the help
      of the temporal convolution system. In combination with the bandwidth compression
      capability of the ASOPS scheme, up to 28-GHz RF spectrum can be directly read out
      by an acquisition system with bandwidth as low as 20 MHz. The experimental
      results demonstrated about 100-MHz resolution and 28-GHz observation bandwidth.
      The resolution can be improved by increasing the amount of temporal dispersion or
      optical spectral bandwidth, and the bandwidth can be further extended by
      compensating the higher-order dispersion, although it is currently mainly limited
      by that of the electro-optic modulator. The frame rate is flexibly tunable by
      changing the repetition rate difference between the two mode-locked fiber lasers.
      Moreover, nearly 25-dB dynamic range indicates this system has a promising
      application prospect.

PMID- 30119380
TI  - Optimization for vertically scanning terahertz attenuated total reflection
      imaging.
AB  - Terahertz attenuated total reflection imaging has been used to develop
      preliminary applications without any in-depth analysis of the nature of present
      systems. Based on our proposed vertically scanning imaging system, an analysis of
      optimum prism design and polarization selection for error reduction is presented
      theoretically and experimentally, showing good agreement. By taking the secondary
      reflection inside the prism and the prism deflection into consideration, p
      polarized terahertz waves are recommended for prisms with a base angle below 31
      degrees , leading to minimum error. This work will contribute to the development
      of more practical application of terahertz attenuated total reflection scanning
      imaging in various fields with enhanced performance.

PMID- 30119381
TI  - Ultrathin graphene diaphragm-based extrinsic Fabry-Perot interferometer for ultra
      wideband fiber optic acoustic sensing.
AB  - An ultra-wideband fiber optic acoustic sensor based on graphene diaphragm with a
      thickness of 10nm has been proposed and experimentally demonstrated. The two
      reflectors of the extrinsic Fabry-Perot interferometer is consist of fiber
      endface and graphene diaphragm, and the cavity is like a horn-shape. The radius
      of the effective area of the ultrathin graphene diaphragm is 1mm. Attributed to
      the strong van der Waals force between the diaphragm and the ceramic ferrule, the
      sensor head can be applied not only in the air but also underwater. Experimental
      results illustrate that ultra-wideband frequency response is from 5Hz to 0.8MHz,
      covering the range from infrasound to ultrasound. The noise-limited minimum
      detectable pressure level of 0.77Pa/Hz1/2@5Hz and 33.97MUPa/Hz1/2@10kHz can be
      achieved, and the applied sound pressure is 114dB and 65.8dB, respectively. The
      fiber optic acoustic sensor may have a great potential in seismic wave
      monitoring, photoacoustic spectroscopy and photoacoustic imaging application due
      to its compact structure, simple manufacturing, and low cost.

PMID- 30119382
TI  - Dual-signal-resonant optical parametric oscillator intracavity driven by a
      coaxially end-pumped laser with compound gain media.
AB  - A flexible method of generating stable dual-wavelength laser pulses with tunable
      power ratio and pulse interval is proposed, through integrating a coaxially end
      pumped laser with compound gain media and an intracavity pumped optical
      parametric oscillator (IOPO). A theoretical model was built by a set of time
      domain coupling wave equations containing both the generation of two fundamental
      waves from a shared pump source and the conversion to signal waves through the
      parametric process. Simulations showed that by simply varying the pump focal
      position or pump wavelength, the gains in two laser crystals could be changed,
      leading to simultaneous change in average power ratio and time interval between
      two wavelengths. Experimental verifications were performed with combined laser
      crystals (Nd:YAG and a-cut Nd:YLF) and a nonlinear crystal (KTA), which enabled
      dual-wavelength signal output in the 1.5-1.6 MUm eye-safe region and demonstrated
      coincident conclusions with theoretical results. As there was no gain competition
      between two fundamental waves, stable signal output was obtained. Moreover,
      various wavelength pairs in any wavelength ranges are possible by using different
      laser crystals and nonlinear crystals. It is believed that this is a promising
      method for generating simultaneous dual-wavelength laser pulses for applications
      in lidar, remote sensing, nonlinear frequency conversion, etc.

PMID- 30119383
TI  - Broadband high-spectral-resolution ultraviolet-visible coherent-dispersion
      imaging spectrometer.
AB  - A coherent-dispersion imaging spectrometer combining imaging, interferometric
      spectroscopy and dispersive spectroscopy is presented, which is a unique concept
      to greatly reduce the multiplex disadvantage of existing ultraviolet-visible
      multiplexed spectroscopy while achieving imaging combined with high spectral
      resolution (e.g., 0.01 nm at 220 nm together with 0.1 nm at 700 nm, or higher)
      for a broadband spectral range. Each unit of the entrance slit is imaged on a
      given column of a detector, and different wavelengths are dispersed across
      different rows of that column. For each slit unit, multiple interferograms are
      generated simultaneously in one scan period, each interferogram with a separate
      wavelength range and located in a separate pixel of the detector. The expressions
      for the coherent-dispersion imaging are given, the preliminary design
      calculations are illustrated by an example, and the numerical simulations for the
      interferogram and spectrum are shown. This design will be suitable for broadband
      high-spectral-resolution ultraviolet-visible spectral imaging.

PMID- 30119384
TI  - Design method for freeform optical systems containing diffraction gratings.
AB  - A design method for freeform optical systems containing diffraction gratings is
      developed based on Fermat's principle and Ludwig's grating ray-tracing equation.
      The proposed method can calculate fine starting-points for diffraction-grating
      based imaging spectrometers with high performance and novel geometries. It can
      also be extended to design optical systems that contain other dispersive
      elements, such as prisms and diffractive optics. Two freeform imaging
      spectrometers are designed by this method to meet the diffraction-limited
      specifications.

PMID- 30119385
TI  - Edge-lit LCD backlight unit for 2D local dimming.
AB  - Local dimming technology has been highly desired for integration with liquid
      crystal displays (LCDs) in order to improve their contrast ratios (CRs) as well
      as to overcome power efficiency bottlenecks. In this paper, we propose and
      demonstrate a slim (~1 mm) edge-lit LCD backlight unit (BLU) capable of 2D local
      dimming. We designed a semi-partitioned light guide plate (LGP) patterned with
      inverse-trapezoidal microstructures, which allows the ultra-slim BLU to function
      without prism sheets. Since light emitting diodes (LEDs) are placed in the middle
      of the LGP, the BLU can freely define illuminated areas and the whole BLU can be
      modularly expanded like a tile canvas. The fabricated BLU achieves uniformity in
      both local and global luminance distributions, as well as in high local dimming
      performance. Experimentally, the BLU increases the CR of the display up to two
      orders of magnitude compared to conventional BLUs.

PMID- 30119386
TI  - Guiding and binding of cavity photons with patterned two-dimensional
      semiconductors.
AB  - Strong optical responses of two-dimensional (2D) semiconductors like transition
      metal dichalcogenides (TMDs) draw substantial attention for prospective
      applications in optoelectronics and photonics. Here, we propose a potentially
      attractive application avenue via embedding patterns of 2D semiconductors
      (shaped, e.g., as strips or disks) in planar optical microcavities to engineer
      photonic modes in the dissipation-free spectral range below the optical gap.
      While the cavity confines electromagnetic fields to its interior, the high in
      plane polarizability of 2D materials causes the appearance of the cavity modes
      that are bound to the patterned pieces in the lateral directions along the
      cavity. A TMD strip would then act to guide such bound cavity photons, while a
      pair of neighboring strips could operate similar to coupled photonic waveguides.
      Our calculations relying on experimentally measured TMD optical suspectibilities,
      explicitly demonstrate this type of behavior accompanied by photonic binding
      energies on the order of 10 meV and micron-scale spatial extents. They indicate
      that patterned 2D semiconductor structures employed within microcavities could
      represent a new material platform to enable various functionalities of integrated
      photonics.

PMID- 30119387
TI  - Performance of single-photons communication using the multi-channel frequency
      coding scheme.
AB  - In this paper, optical communication at the single-photon level is experimentally
      demonstrated by using a multi-channel frequency coding scheme in which the
      information is decoded by using the single-photons modulation spectrum. By using
      the modulation spectrum, the coding scheme could work normally in a channel with
      high loss and noise. Besides, multiple modulation frequency components could be
      used in a wide bandwidth regardless of frequency aliasing; therefore, the multi
      channel frequency coding scheme makes it possible for high-capacity single
      photons communication.

PMID- 30119388
TI  - Optimal spatial bandwidth capacity in multiplexed off-axis holography for rapid
      quantitative phase reconstruction and visualization: erratum.
AB  - We correct a typo that repeated itself in several equations. Our previous results
      and conclusions are unchanged.

PMID- 30119389
TI  - Sparsity-based super-resolution microscopy from correlation information: erratum.
AB  - Two references on sparse deconvolution of high-density fluorescence microscopy
      images are added to [Opt. Express26(14), 18238 (2018)].

PMID- 30119390
TI  - Jones calculus modeling and analysis of the thermal distortion in a Ti:sapphire
      laser amplifier: erratum.
AB  - Equations 41-44 in our paper [ Opt. Express26, 14362 (2016)] contain errors. We
      correct the equations in this erratum.

PMID- 30119391
TI  - Experimental generation and analysis of chaos-modulated pulses for pulsed chaos
      lidar applications based on gain-switched semiconductor lasers subject to optical
      feedback.
AB  - We experimentally generate and analyze chaos-modulated pulses for pulsed chaos
      lidar applications based on gain-switched semiconductor lasers subject to optical
      feedback. While conventional pulsed lidars emit repetitive short pulses without
      specificity making them vulnerable to interference and range ambiguity, chaos
      lidars possess the advantages of having no range ambiguity and being immune to
      interference and jamming, which are benefits of the aperiodic and uncorrelated
      waveforms we use. Compared to the cw chaos lidars originally proposed, the pulsed
      chaos lidars can have significantly higher peak power under the class-1 eye-safe
      regulation that is essential for long-range low-reflectivity target detection. We
      investigate the temporal, spectral, and cross-correlation characteristics of the
      modulated pulses obtained with different feedback strengths and modulation
      currents. Induced by the transient response and evolving with the delayed
      feedback, modulated pulses exhibiting periodic oscillations and complex dynamics
      such as chaos are observed. Under a weakly damped condition with large modulation
      current and moderate feedback strength, we successfully generate uncorrelated
      chaos-modulated pulses suitable for the pulsed chaos lidar applications. With the
      current configuration, for cross-correlations comparable to the benchmark of 0.19
      set by the cross-correlation of the intensity fluctuation on the sole gain
      switched pulses without feedback, uncorrelated waveforms with durations up to 218
      ns in a 500 ns modulated pulse can be effectively utilized.

PMID- 30119392
TI  - Compositionally controlled plasmonics in amorphous semiconductor metasurfaces.
AB  - Amorphous bismuth telluride (Bi:Te) provides a composition-dependent, CMOS
      compatible alternative material platform for plasmonics in the ultraviolet
      visible spectral range. Thin films of the chalcogenide semiconductor are found,
      using high-throughput physical vapor deposition and characterization techniques,
      to exhibit a plasmonic response (a negative value of the real part of relative
      permittivity) over a band of wavelengths extending from ~250 nm to between 530
      and 978 nm, depending on alloy composition (Bi:Te at% ratio). The plasmonic
      response is illustrated via the fabrication of subwavelength period nano-grating
      metasurfaces, which present strong, period-dependent plasmonic absorption
      resonances in the visible range, manifested in the perceived color of the
      nanostructured domains in reflection.

PMID- 30119393
TI  - Fully embedded photonic crystal cavity with Q=0.6 million fabricated within a
      full-process CMOS multiproject wafer.
AB  - A two dimensional photonic crystal (PhC) resonator, based on a recent design
      concept, entirely embedded in Silica, is fabricated in a CMOS full-process
      multiproject wafer, including additional steps such as implantation,
      metalization, Germanium deposition and planarization. A large loaded Q-factor
      (5.9 * 105) is achieved without removal of the silica cladding. A statistical
      analysis over 56 devices leads to an average value for the loaded Q of 4 * 105,
      in close agreement with calculations. An upper boundary for the fabrication
      disorder is estimated to 1.2 nm.

PMID- 30119394
TI  - CMOS compatible all-silicon TM pass polarizer based on highly doped silicon
      waveguide.
AB  - We propose and analyze via simulation a novel approach to implement a
      complementary metal-oxide-semiconductor compatible and high extinction ratio
      transverse magnetic pass polarizer on the silicon-on-insulator platform with a
      340 nm thick silicon core. The TM-pass polarizer utilizes a highly doped p
      silicon waveguide as the transverse hybrid plasmonic waveguide. We observed an
      extinction ratio of 30.11 dB and an insertion loss of 3.08 dB for a device length
      of 15 um. The fabrication process of the proposed TM-pass polarizer is simpler
      compared to the state-of-the-art since it only uses silicon waveguides and does
      not require any special material or feature size.

PMID- 30119395
TI  - Time-stretch probing of ultra-fast soliton dynamics related to Q-switched
      instabilities in mode-locked fiber laser.
AB  - Ultra-fast soliton dynamics is one of the most attractive phenomena in the mode
      locked fiber laser. However, the formation and breakup of solitons are difficult
      to observe, due to the transient nature of the process. Using the time-stretch
      technique, we are able to trace the real-time evolution of the soliton bound
      state formation and mode-locking build-up. Q-switched instabilities exist in both
      booting processes. Moreover, we find that the evolving patterns of soliton bound
      states are highly dependent on their initial conditions. Here, two types of
      soliton pairs are observed in the cavity and their typical forming dynamics are
      recorded and analyzed. Our findings uncover a diverse set of soliton dynamics in
      a mode-locked fiber laser and thus promote our understandings about complex
      dynamics in nonlinear optical systems. These results also provide a valuable
      reference for further theoretical studies.

PMID- 30119396
TI  - Temporal multiplexing of the scientific grade camera for hyper-frame-rate
      imaging.
AB  - In order to maximize the spatio-temporal resolution of the scientific grade
      camera at width-limited ROI, this paper proposes a new hyper-frame-rate imaging
      method by temporal multiplexing the sub-region of the image sensor. In the
      system, a dual-axis scanning galvanometer is localized at the relay pupil plane
      and a high quality scan lens is utilized to form an image-side telecentric path.
      Following this path can overcome bandwidth waste in the conventional exposure and
      readout mode, and maintain other performances of image sensors. As a result, the
      sCMOS camera has performed 432fps over 820 * 700 pixel arrays to record the
      dynamic heartbeat of zebrafish larvae.

PMID- 30119397
TI  - Water film thickness imaging based on time-multiplexed near-infrared absorption.
AB  - We demonstrate the imaging of the thickness of liquid water thin films in the 100
      1500 um range at a constant temperature by monitoring the pixel-by-pixel ratio of
      absorbance at two near-infrared (NIR) wavelengths near 1400 nm detected with a
      fast framing InGaAs focal-plane array camera. Experiments were performed in
      reflection mode with films of pure water and water/ethanol mixtures supported on
      opaque surfaces using two illumination-detection configurations. One scheme uses
      specular reflection of incident and reflected linearly polarized diode-laser
      light at Brewster's angle, which enables detection of signal light that has twice
      traversed the liquid film with negligible interference from unwanted partial
      reflections of the incoming beams at the front surface interfaces (air/window and
      window/water for films constrained by a cover plate or air/water for free
      standing films). The second configuration located the detection camera
      perpendicular above the surface where the detected light was transmitted through
      the sample and diffusely scattered from the support surface. Imaging measurements
      of film thickness using both configurations were successfully demonstrated. Time
      resolved measurements capture the dynamics of flowing water films or waves
      generated by droplet impingement.

PMID- 30119398
TI  - Ultra-broadband wide-angle linear polarization converter based on H-shaped
      metasurface.
AB  - We report the design, fabrication, and measurement of an ultra-broadband wide
      angle reflective cross-polarization convertor using the compact H-shaped
      metasurface. The significant bandwidth expansion is attributed to the four
      electromagnetic resonances generated in an H-shaped unit. The simulation results
      show that the polarization conversion ratio (PCR) of the proposed metasurface is
      above 90% in the frequency range from 7 to 19.5 GHz and the relative bandwidth
      reaches 94%. The proposed metasurface is valid for a wide range of incident
      angles, and the mean polarization conversion ratio remains 80% even though the
      incident angle reaches 41.5 degrees . The experimental results are in good
      agreement with the simulation results. Compared with the previous designs, the
      proposed linear polarization converter has a simple geometry but an excellent
      performance and hence has potential applications in microwave communications,
      remote sensors, and imaging systems.

PMID- 30119399
TI  - Three-dimensional super-resolution high-throughput imaging by structured
      illumination STED microscopy.
AB  - Stimulated emission depletion (STED) microscopy is able to image fluorescence
      labeled samples with nanometer scale resolution. STED microscopy is typically a
      point-scanning method, limited by the high intensity requirement of the depletion
      beam. With the development of high peak power lasers, two dimensional parallel
      STED microscopy has been developed. Here, we develop the theoretical basis for
      extending STED microscopy to three dimensional imaging in parallel. This method
      uses structured illumination (SI) to generates a three dimensional depletion
      pattern. Compared to the two dimensional parallel STED microscopy, the 3D SI-STED
      microscopy generates intensity modulation along the light propagation direction
      without requiring higher laser power. This method not only achieves axial super
      resolution of STED microscopy but also greatly reduces photobleaching and
      photodamage for 3D volumetric imaging.

PMID- 30119400
TI  - Photonic Weyl phase transition in dynamically modulated brick-wall waveguide
      arrays.
AB  - We investigate the topological phase transition between Type-I and Type-II Weyl
      points (WPs) in a composite three-dimensional lattice composed of a two
      dimensional brick-wall waveguide array and a synthetic frequency dimension
      created by dynamic modulation. By imposing different modulation amplitudes and
      phases in the two sublattices, we can break either parity or time-reversal
      symmetry and realize the phase transition between Type-I and Type-II WPs. As the
      array is truncated to have two edges, two Fermi-arc surface states will emerge,
      which propagate in opposite directions for Type-I WPs while in same directions
      for Type-II WPs, accompanied by bidirectional and unidirectional frequency shifts
      for the optical modes. Particularly at the phase transition point, we find that
      one of two bands becomes flat with a vanished group velocity along frequency axis
      in the vicinity of WPs. The study paves a way towards realizing different
      topological phases in the same photonic structure, which offers new opportunities
      to control wave transportation both in spatial and frequency domains.

PMID- 30119401
TI  - Tomographic laser absorption imaging of combustion species and temperature in the
      mid-wave infrared.
AB  - In this work, laser absorption spectroscopy techniques are expanded in spatial
      resolution capability by utilizing a high-speed infrared camera to image flow
      fields backlit with tunable mid-wave infrared laser radiation. The laser
      absorption imaging (LAI) method yields spectrally-resolved and spatially-rich
      datasets from which quantitative species and temperature profiles can be
      generated using tomographic reconstruction. Access to the mid-wave infrared (3-5
      um) enables imaging of fuels, intermediates, and products of combustion in
      canonical small-diameter flames (< 1 cm). Example 1D measurements and 2D
      reconstructions of ethane (3.34 um), carbon monoxide (4.97 um), and carbon
      dioxide (4.19 um) in an axisymmetric laminar flame are presented and discussed.
      LAI is shown to significantly enhance spatio-temporal data bandwidth (~400
      simultaneously sampled lines-of-sight) and resolution (~50 um) compared to other
      tomographic absorption spectroscopy techniques, and with a simplified optical
      arrangement.

PMID- 30119402
TI  - Modulation-nonmodulation pyramid wavefront sensor with direct gradient
      reconstruction algorithm on the closed-loop adaptive optics system.
AB  - A modulation-nonmodulation pyramid wavefront sensor with direct gradient
      reconstruction algorithm using on the adaptive optics is reported in this paper.
      This means that the interaction matrix of the system is obtained by using a
      modulated pyramid and the closed-loop control process is performed with a
      nonmodulated pyramid. The theoretical basis and simulation analysis of the direct
      gradient reconstruction algorithm are described in detail, and laboratory results
      show that the pyramid wavefront sensor based on this algorithm can work as
      expected in a closed-loop adaptive optics system.

PMID- 30119403
TI  - Laser direct-writing lithography equipment system for rapid and MUm-precision
      fabrication on curved surfaces with large sag heights.
AB  - A novel laser direct writing lithography equipment system was proposed to realize
      rapid and MUm-precision fabrication on curved surfaces with large curvatures and
      large sag heights. Through detailed design, analysis, simulation, and
      measurement, it showed that the system was able to continuously, linearly and
      rapidly change the focus position in z coordinate. For demonstration, a
      concentric-circular photoresist grating with a sag height of 5.2 mm and a
      designed line width/space of 12.5 MUm/25 MUm was fabricated within 40 s on a
      convex K9 glass substrate surface with a curvature radius of 32.77 mm. When
      combining with the movement of the x-y-z stage, the system could fabricate the
      micropatterns on curved surfaces with larger dimensions. Further, the system
      possessed the general principles of optics, mechanics, and automation for MUm
      precision 3D microfabrication.

PMID- 30119404
TI  - Full-field thickness measurement of ultrathin liquid film in receding contact
      induced nano-channel using surface plasmon resonance.
AB  - This research demonstrates that a surface plasmon resonance (SPR) imaging
      technique can effectively measure full-field nanoscale thickness of a liquid
      water film filled in the receding contact-induced nano-channel. To the authors'
      knowledge this has not been demonstrated previously. Experimental calibration has
      been conducted by measuring surface plasmon resonance reflectance depending on
      the piezometer-controlled water nano-film thickness and comparing the
      experimental results with the theoretical calculations to show very good
      agreement. The measured full-field thickness profiles significantly visualize the
      three-dimensional nano-channel formation filled with liquid water film. It shows
      that the sensitivity and the resolution in thickness measurement are estimated as
      1.21 pixel gray level/nm and 2.5 nm, respectively. The experimentally observed
      resolution is around 10 nm given the uncertainty in the demonstrated full-field
      mapping of thickness. From this research, it is demonstrated that SPR imaging
      successfully measures the thickness of ultrathin liquid film especially below 85
      nm in full-field under normal conditions and can effectively characterize the
      three-dimensional nano-channel formation during the receding contact process.

PMID- 30119405
TI  - Full control of conical beam carrying orbital angular momentum by reflective
      metasurface.
AB  - Conical beams have recently attracted much attention due to their excellent
      performances and potential applications in wireless and satellite-based
      communication technology. Here, reflective metasurfaces composed of Pancharatnam
      Berry (PB) phase elements are demonstrated to have the ability to be flexible and
      to fully control the conical beam generation with desirable orbital angular
      momentum (OAM) modes. The theoretical model is developed to analyze the behavior
      of the conical beam radiation from the reflective metasurface and especially to
      predict the cone angle, one of the most important factors in the conical beam
      design. Analysis shows that arbitrary combinations of the cone angle and the OAM
      mode can be obtained by synthesizing the spatial phase distribution of the
      metasurface. Finally, two prototypes of microwave metasurfaces, with working
      bands from 14 GHz to 17 GHz, are fabricated and measured, and the results agree
      well with the theoretical predictions and simulations. This work demonstrates
      that metasurfaces can be used for controlling the conical beam generation with
      desirable OAM modes to potentially enable high capacity data communication,
      paving the way for novel devices with an appealing low-profile in wireless
      communication applications.

PMID- 30119406
TI  - Effect of the surface roughness on X-ray absorption by mirrors operating at
      extremely small grazing angles.
AB  - This study theoretically analyzes an increase in X-ray absorption by a grazing
      incidence mirror due to its surface roughness. We demonstrate that the increase
      in absorption can be several hundred times larger than predicted by the Nevot
      Croce formula. As a result, absorption enhances by several times compared to a
      perfectly smooth mirror despite the extremely small grazing angle of an incident
      X-ray beam (a fraction of the critical angle of the total external reflection)
      and the high quality of the reflecting surface (the roughness height was 0.5 nm
      in modeling). The main contribution to the absorption increase was dictated by
      the mid-scale roughness (waviness) of the virgin substrate surface, whose quality
      thus defines an absorption enhancement. The approach was applied to the analysis
      of two real mirrors used in a synchrotron (BESSY-I) and a European X-ray free
      electron laser (XFEL) beamline. The modern surface finishing technology of
      elastic emission machining provides extremely low substrate waviness,
      guaranteeing the negligible effect of the surface roughness on the absorption
      increase.

PMID- 30119407
TI  - Far-field propagation of partially coherent laser light in random mediums:
      erratum.
AB  - We present a correction to a typographical error in Eq. (27) and Eq. (28) in our
      article of [Opt. Express 26, 15609 (2018)].

PMID- 30119408
TI  - Eavesdropping and countermeasures for backflash side channel in quantum
      cryptography.
AB  - Quantum key distribution (QKD) promises information theoretic secure key as long
      as the device performs as assumed in the theoretical model. One of the
      assumptions is an absence of information leakage about individual photon
      detection outcomes of the receiver unit. Here we investigate the information
      leakage from a QKD receiver due to photon emission caused by detection events in
      single-photon detectors (backflash). We test commercial silicon avalanche
      photodiodes and a photomultiplier tube, and find that the former emit
      backflashes. We study the spectral, timing and polarization characteristics of
      these backflash photons. We experimentally demonstrate on a free-space QKD
      receiver that an eavesdropper can distinguish which detector has clicked inside
      it, and thus acquire secret information. A set of countermeasures both in theory
      and on the physical devices are discussed.

PMID- 30119409
TI  - Frequency domain diffuse optical spectroscopy with a near-infrared tunable
      vertical cavity surface emitting laser.
AB  - We present an approach for performing frequency domain diffuse optical
      spectroscopy (fd-DOS) utilizing a near-infrared tunable vertical cavity surface
      emitting laser (VCSEL) that enables high spectral resolution optical sensing in a
      miniature format. The tunable VCSEL, designed specifically for deep tissue
      imaging and sensing, utilizes an electrothermally tunable microelectromechanical
      systems topside mirror to tune the laser cavity resonance. At room temperature,
      the laser is tunable across 14nm from 769 to 782nm with single mode CW output and
      a peak output power of 1.3mW. We show that the tunable VCSEL is suitable for use
      in fd-DOS by measuring the optical properties of a tissue-simulating phantom over
      the tunable range. Optical properties were recovered within 0.0006mm-1
      (absorption) and 0.09mm-1 (reduced scattering) compared to a broadband fd-DOS
      reference system. Our results indicate that tunable VCSELs may be an attractive
      choice to enable high spectral resolution optical sensing in a wearable format.

PMID- 30119410
TI  - Advancement of X-ray radiography using microfocus X-ray source in conjunction
      with amplitude grating and SOI pixel detector, SOPHIAS.
AB  - We show how to improve microfocus X-ray radiography by using the SOPHIAS silicon
      on-insulator pixel detector in conjunction with an amplitude grating. Single
      exposure multi-energy absorption and differential phase contrast imaging was
      performed using the single amplitude grating method. The sensitivity in
      differential phase contrast imaging in a two-pixel-pitch setup was enhanced by
      39% in comparison with the previously reported method [Rev. Sci. Instrum. 81,
      113702 (2010).] by analyzing charge-sharing effects. Small-angle-scattering
      imaging was also possible in the two-pixel-pitch setup by counting the number of
      X-ray photons passing the pixel boundaries.

PMID- 30119411
TI  - Aberration recovery by imaging a weak diffuser.
AB  - We present a computational method for field-varying aberration recovery in
      optical systems by imaging a weak (index-matched) diffuser. Using multiple images
      acquired under plane wave illumination at distinct angles, the aberrations of the
      imaging system can be uniquely determined up to a sign. Our method is based on a
      statistical model for image formation that relates the spectrum of the speckled
      intensity image to the local aberrations at different locations in the field-of
      view. The diffuser is treated as a wide-sense stationary scattering object,
      eliminating the need for precise knowledge of its surface shape. We validate our
      method both numerically and experimentally, showing that this relatively simple
      algorithmic calibration method can be reliably used to recover system aberrations
      quantitatively.

PMID- 30119412
TI  - Arbitrary energy-preserving control of the line spacing of an optical frequency
      comb over six orders of magnitude through self-imaging.
AB  - Spectral self-imaging (SI) is an efficient technique for controlling the line
      spacing (LS) of optical frequency combs (OFC). However, the degree of control is
      relatively limited, since the LS of the output comb must be set to be an integer
      sub-multiple of the input one. This technique can be extended to achieve
      arbitrary control of the comb LS by pre-conditioning the input comb with a
      properly designed spectral phase mask. This way, the output LS can be set to be
      any desired integer or fractional multiple of the input one. This generalized
      spectral SI process is intrinsically energy-preserving, which enables passive
      amplification of individual spectral lines of the comb when the scheme is
      designed for LS increase. Here we demonstrate the unique capabilities of
      generalized spectral SI in a simple dedicated fiber-optics platform, based on a
      frequency-shifting recirculating loop. When seeded with an external CW laser, the
      loop delivers a frequency comb with an arbitrary and reconfigurable quadratic
      spectral phase. We report lossless arbitrary control of the LS of the generated
      OFCs over six orders of magnitude, from the kHz to the GHz range, including
      passive amplification of individual comb lines by factors as high as 17 dB. The
      LS control is produced without modifying the features of the frequency comb.
      Practical applications of this LS control method are discussed.

PMID- 30119413
TI  - Magnetoplasmonic crystal waveguide.
AB  - We propose a perspective type of insulator-metal-insulator magnetoplasmonic
      crystal waveguide, composed of a gold grating placed between two garnet layers.
      Using an original non-perturbing method for the deposition of the upper magneto
      dielectric layer, we fabricate the samples and provide experimental results
      evidencing the coupling of surface plasmon-polaritons propagating on the opposite
      Au/garnet interfaces. In contrast to traditional Au/garnet magnetoplasmonic
      crystals, spectra of the magneto-optical effect measured in transmission through
      this waveguide demonstrate rather specific features: a high-quality resonance for
      the long-range surface plasmon-polariton and a broad 60 nm wide resonance for the
      short-range surface plasmon-polariton. Our findings open new routes towards the
      development of high-sensitivity robust magnetoplasmonic sensors.

PMID- 30119414
TI  - Multifunctional binary diffractive optical elements for structured light
      projectors.
AB  - A set of diffractive optical elements for multiple-stripe structured illumination
      was designed, fabricated and characterized. Each of these elements with a single
      layer of binary surface relief combines functions of a diffractive lens, Gaussian
      to-tophat beam shaper, and Dammann beam splitter. The optical investigations of
      laser light patterns at 20 degrees  fanout angle reveal up to 88% diffraction
      efficiency, high contrast, and nearly diffraction limited resolution. The
      developed technology has the potential for reducing complexity, number of optical
      components, power consumption and costs of structured light projectors in mobile
      and stationary 3D sensors.

PMID- 30119415
TI  - Investigation about the influence of longitudinal-mode structure of the laser on
      the relative intensity noise properties.
AB  - The influence of the longitudinal-mode structure (LMS) of the laser on the
      relative intensity noise (RIN) properties was investigated in this paper after an
      all-solid-state continuous-wave (CW) single-frequency 1064 nm laser with output
      power of 50.3 W was achieved. The LMS of the laser was manipulated by controlling
      the temperature of the nonlinear lithium triborate (LBO) crystal deliberately
      introduced to the resonator. When the laser worked with single-longitudinal-mode
      (SLM) operation, the stable RIN spectrum was observed and measured. Moreover,
      with the decrease of the nonlinear conversion efficiency (NCE), the frequency and
      amplitude of the resonant-relaxation oscillation (RRO) peak regularly shifted to
      the higher frequencies and increased, respectively. However, with further
      decrease of the NCE, the laser began to work with the multi-longitudinal-mode
      (MLM) or mode-hopping operation and the unstable RIN spectra of the laser were
      both observed not only at low frequencies but also at high frequencies. Once the
      NCE was moved away, the MLM or mode-hopping can only enhance the fluctuation of
      the laser RIN spectrum at the low frequencies (lower than the frequency of RRO).
      The experimental results directly revealed the relationship between the LMS of
      the laser and the RIN spectra, and confirmed definitely that the key to achieve a
      stable high power laser with low intensity noise was to realize single-frequency
      operation of the laser with free MLM and mode-hopping.

PMID- 30119417
TI  - Filamentary anemometry using femtosecond laser-extended electric discharge -
      FALED.
AB  - We demonstrate a non-contact spatiotemporally resolved comprehensive method for
      gas flow velocity field measurement: Filamentary Anemometry using femtosecond
      Laser-extended Electric Discharge (FALED). A faint thin plasma channel was
      generated in ambient air by focusing an 800-nm laser beam of 45 fs, which was
      used to ignite a pulsed electric discharge between two electrodes separated over
      10 mm. The power supplier provided a maximum voltage up to 5 kV and was operated
      at a burst mode with a current duration of less than 20 ns and a pulse-to-pulse
      separation of 40 MUs. The laser-guided thin filamentary discharge plasma column
      was blowing up perpendicularly by an air jet placed beneath in-between the two
      electrodes. Although the discharge pulse was short, the conductivity of the
      plasma channel was observed to sustain much longer, so that a sequence of
      discharge filaments was generated as the plasma channel being blown up by the jet
      flow. The sequential bright thin discharge filaments can be photographed using a
      household camera to calculate the flow velocity distribution of the jet flow. For
      a direct comparison, a flow field measurement using FLEET [Appl. Opt. 50, 5158
      (2011)] was also performed. The results indicate that the FALED technique can
      provide instantaneous nonintrusive flow field velocity measurement with good
      accuracy.

PMID- 30119416
TI  - Optimization of a quantum weak measurement system with its working areas.
AB  - Phase-sensitive weak measurement systems have been receiving an increasing amount
      of attention. In this paper, we introduce a series of weak measurement working
      areas. By adjusting the pre-selection and post-selection states and the total
      phase difference between vertically polarized light and horizontally polarized
      light, the measurement of the weak value is amplified by several times in one
      system. Its applicability is verified in a label-free total internal reflection
      system. The original sensitivity and resolution are improved at different working
      areas, reaching 1.85 um/refractive index unit (RIU) and 6.808 * 10-7 RIU,
      respectively.

PMID- 30119418
TI  - Multispectral and large bandwidth achromatic imaging with a single diffractive
      photon sieve.
AB  - Conventional photon sieves suffer from large chromatic aberration due to
      diffractive nature and can image only at a single designed wavelength with near
      zero bandwidth. Here, a novel photon sieve that can image achromatically and
      simultaneously at multiple wavelengths with wide spectral bandwidth is proposed
      and demonstrated experimentally. The multispectral achromatic imaging with a
      single diffractive photon sieve is implemented with harmonic diffraction and
      wavefront coding, in which harmonic diffraction makes different diffracted orders
      of multiple harmonic wavelengths on a common focus while wavefront coding through
      the coded distribution of the pinholes expands the bandwidth of diffracted
      imaging. Numerical simulations show that when four spectral bands centered at
      437.5, 500, 583.3, and 700 nm in the visible range is designed with a cubic
      wavefront coding parameter alpha = 30pi and a harmonic diffraction order of 5,
      the bandwidth at the corresponding wavelength band can reach +/- 8, +/- 9, +/- 11
      and +/- 14 nm respectively, and the total working bandwidth of the harmonic
      diffraction wavefront coded photon sieve reaches ~84 nm compared with 0.39 nm of
      the conventional one. Experimental validation was performed using an UV
      lithography fabricated wavefront coded photon sieve of a focal length of 500 mm
      and a diameter of 50 mm at a designed wavelength of 700 nm. The results show
      excellent agreement with the theoretical predictions.

PMID- 30119419
TI  - Quantum manipulation of biphoton spectral distributions in a 2D frequency space
      toward arbitrary shaping of a biphoton wave packet.
AB  - Arbitrary shaping of optical waveform is fundamental interest from basic science
      to advanced optical technologies. However, it is still challenging task for
      shaping a biphoton wave packet. Here we experimentally manipulate the spectrum
      and phase of a biphoton wave packet in a two-dimensional frequency space. The
      spectrum is shaped by adjusting the temperature of the crystal, and the phase is
      controlled by tilting the dispersive glass plate. The manipulating effects are
      confirmed by measuring the two-photon spectral intensity (TSI) and the Hong-Ou
      Mandel (HOM) interference patterns. The technique in this work paves the way for
      arbitrary shaping of a multi-photon wave packet in a quantum manner.

PMID- 30119420
TI  - Strategy of optical negative feedback for narrow linewidth semiconductor lasers.
AB  - The coherent optical negative feedback scheme is systematically investigated by
      calculating rate equations that model a noise-added semiconductor laser coupled
      to a Fabry-Perot optical filter for the FM noise reduction. The calculated
      results indicate that the FM noise is minimized when a lasing frequency of the
      free-running laser matches a valley frequency of the filter (the point where
      power reflectivity becomes zero) under a specific feedback phase, where the slope
      of the electric field reflectivity for the lasing light and frequency
      discrimination efficiency to electric field amplitude of the feedback light
      becomes maximum. And the linewidth is also minimized at a lasing frequency
      corresponding to the valley frequency of the Fabry-Perot optical filter. It is
      also made clear that the laser frequency becomes less sensitive to the
      fluctuation of the injection current of the laser under optical negative
      feedback.

PMID- 30119421
TI  - Two-parameter-SOP and three-parameter-RSOP fiber channels: problem and solution
      for polarization demultiplexing using Stokes space.
AB  - In this paper, we highlight that it is inadequate to describe the rotation of the
      state of polarization (RSOP) in a fiber channel with the 2-parameter description
      model, which was mostly used in the literature. This inadequate model may result
      in problems in polarization demultiplexing (PolDemux) because the RSOP in a fiber
      channel is actually a 3-parameter issue that will influence the state of
      polarization (SOP) of the optical signal propagating in the fiber and is
      different from the 2-parameter SOP itself. Considering three examples of the 2
      parameter RSOP models typically used in the literature, we provide an in-depth
      analysis of the reasons why the 2-parameter RSOP model cannot represent the RSOP
      in the fiber channel and the problems that arise for PolDemux in the coherent
      optical receiver. We present a 3-parameter solution for the RSOP in the fiber
      channel. Based on this solution, we propose a DSP tracking and equalization
      scheme for the fast time-varying RSOP using the extended Kalman filter (EKF). The
      proposed scheme is proved to be universal and can solve all the PolDemux problems
      based on the 2- or 3-parameter RSOP model and exhibits good performance in the
      time-varying RSOP scenarios.

PMID- 30119422
TI  - Adaptive liquid crystal microlens array enabled by two-photon polymerization.
AB  - A tunable-focus liquid crystal microlens array is demonstrated and characterized.
      Using two-photon polymerization based direct-laser writing, a polymerized
      microlens array is fabricated on one substrate. Such a microlens array creates
      inhomogeneous electric field distribution and homogeneous-like liquid-crystal
      alignment, simultaneously. The phase profile and thus the focal length can be
      tuned dynamically by the applied voltage. We also further investigate the
      focusing property and the imaging capability of the fabricated sample. Using the
      adaptive microlens array as an example, we demonstrate that directly forming a
      curvilinear surface with liquid-crystal alignment is feasible. In addition to
      adaptive lens, this direct-laser writing method is also a powerful tool for
      making other tunable photonic devices.

PMID- 30119423
TI  - Generation of transverse photo-induced voltage in plasmonic metasurfaces of
      triangle holes.
AB  - We experimentally and numerically demonstrate the transverse electrical response
      produced by circularly-polarized light with normal incidence observed as
      transverse photo-induced voltage across the plasmonic metasurface made of
      triangle holes. The measured transverse photo-induced voltage is consistent with
      the calculated acting force on electrons in the metasurface by using the
      Maxwell's stress tensor. The polarity of voltage reverses as the incident spin
      (light helicity) switches from right-handed circular polarization to left-handed
      circular polarization. The origin of the spin-dependent voltage sign is the
      broken symmetries of the electric and magnetic fields in the triangle hole due to
      the opposite circular polarizations. The demonstrated results open up many
      opportunities in further investigating the second-order nonlinear optical effects
      of metamaterials and metasurfaces, and developing applications in high-speed
      photodetectors, polarimeters, and optical sensors.

PMID- 30119424
TI  - Nonlinear generation of Airy vortex beam.
AB  - Recently, hybrid beams have sparked considerable interest because of their
      properties coming from different kinds of beams at the same time. Here, we
      experimentally demonstrate Airy vortex beam generation in the nonlinear frequency
      conversion process when the fundamental wave with its phase modulated by a
      spatial light modulator is incident into a homogeneous nonlinear medium. In our
      experiments, second harmonic Airy circle vortex beams and Airy ellipse vortex
      beams were generated and the topological charge was also measured. The parabolic
      trajectory of those Airy vortex beams can be easily adjusted by altering the
      fundamental wave phase. This study provides a simple way to generate second
      harmonic Airy vortex beams, which may broaden its future use in optical
      manipulation and light-sheet microscopy.

PMID- 30119425
TI  - Multiple-plane image formation by Walsh zone plates.
AB  - A radial Walsh filter is a phase binary diffractive optical element characterized
      by a set of concentric rings that take the phase values 0 or pi, corresponding to
      the values + 1 or -1 of a given radial Walsh function. Therefore, a Walsh filter
      can be re-interpreted as an aperiodic multifocal zone plate, capable to produce
      images of multiple planes simultaneously in a single output plane of an image
      forming system. In this paper, we experimentally demonstrate for the first time
      the focusing capabilities of these structures. Additionally, we report the first
      achievement of images of multiple-plane objects in a single image plane with
      these aperiodic diffractive lenses.

PMID- 30119426
TI  - Scheme for media conversion between electronic spin and photonic orbital angular
      momentum based on photonic nanocavity.
AB  - Light with nonzero orbital angular momentum (OAM) or twisted light is promising
      for quantum communication applications such as OAM-entangled photonic qubits.
      Methods and devices for the conversion of the photonic OAM to photonic spin
      angular momentum (SAM), as well as for the photonic SAM to electronic SAM
      transformation are known but the direct conversion between the photonic OAM and
      electronic SAM is not available within a single device. Here, we propose a scheme
      which converts photonic OAM to electronic SAM and vice versa within a single
      nanophotonic device. We employed a photonic crystal nanocavity with an embedded
      quantum dot (QD) which confines an electron spin as a stationary qubit. The
      confined spin-polarized electrons could recombine with holes to give circularly
      polarized emission, which could drive the rotation of the nanocavity modes via
      the strong optical spin-orbit interaction. The rotating modes then radiate light
      with nonzero OAM, allowing this device to serve as a transmitter. As this can be
      a unitary process, the time-reversed case enables the device to function as a
      receiver. This scheme could be generalized to other systems with a resonator and
      quantum emitters such as a microdisk and defects in diamond for example. Our
      scheme shows the potential for realizing an (ultra)compact electronic SAM
      photonic OAM interface to accommodate OAM as an additional degree of freedom for
      quantum information purposes.

PMID- 30119427
TI  - Topological whispering gallery modes in two-dimensional photonic crystal
      cavities.
AB  - Utilizing the robust transport properties of the topological photonic crystal
      interface, we experimentally realize two-dimensional topological photonic crystal
      cavities, where discrete whispering gallery modes can propagate unidirectionally
      along the cavity circumference. Different from traditional cavities, these
      topological whispering galley modes are insensitive to cavity shapes. Our
      microwave demonstration has a good agreement with numerical simulations. Using
      pure dielectrics, by scaling down to the optical wavelength, an optical
      directional coupler based on the same topological photonic crystal scheme is also
      proposed. We here show that topological photonics can provide more novel designs
      for optical devices.

PMID- 30119428
TI  - High-resolution THz gain measurements in optically pumped ammonia.
AB  - This study is aimed at the evaluation of THz gain properties in an optically
      pumped NH3 gas. NH3 molecules undergo rotational-vibrational excitation by mid
      infrared (MIR) optical pumping provided by a MIR quantum cascade laser (QCL)
      which enables precise tuning to the NH3 infrared transition around 10.3 MUm. Pure
      inversion transitions, (J = 3, K = 3) at 1.073 THz and (J = 4, K = 4) at 1.083
      THz were selected. The THz measurements were performed using a THz frequency
      multiplier chain. The results show line profiles with and without optical pumping
      at different NH3 pressures, and with different MIR tuning. The highest gain at
      room temperature under the best conditions obtained during single pass on the
      (3,3) line was 10.1 dB*m-1 at 26 MUbar with a pumping power of 40 mW. The (4,4)
      line showed lower gain of 6.4 dB*m-1 at 34 MUbar with a pumping power of 62 mW.
      To our knowledge these THz gains are the highest measured in a continuous-wave
      MIR pumped gas.

PMID- 30119429
TI  - Second-order statistics of a partially coherent electromagnetic rotating
      elliptical Gaussian vortex beam through non-Kolmogorov turbulence.
AB  - Based on the extended Huygens-Fresnel principle, analytical formulas for the
      cross-spectral density matrix elements of a partially coherent electromagnetic
      rotating elliptical Gaussian vortex (PCEREGV) beam through non-Kolmogorov
      turbulence are derived and the corresponding second-order statistics are
      investigated numerically. The numerical calculations of the PCEREGV beam are
      first developed to validate the correctness of the analytical results. Our
      findings show that the transverse spectrum density with an initially elliptical
      annular shape splits into two light spots during the beam propagation. By
      choosing appropriate parameters of the beam and the turbulence, we can maximize
      the spectrum density and control the spectral states of coherence and
      polarization so as to alleviate the influence of the turbulent atmosphere
      effectively.

PMID- 30119430
TI  - Monte Carlo simulations of the backscattering measurements for associated
      uncertainty.
AB  - Three-dimensional simulations using the Monte Carlo method are implemented to
      analyze and quantify the uncertainty and the influence of absorption on the
      measurement of light backscattering by ECO-BB9 (WET Labs) sensor for a wide
      variety of optically complex and open ocean waters. The analytical investigation
      of the geometrical configuration revealed a distinct effective path length which
      contributes towards an accurate assessment of absorption effect on the
      backscattering measurement. The present study proposes the application of a non
      linear relationship to determine the measured parameter from the detector counts
      more accurately than the conventional method that applies the scale factor. It
      was found that the mean centroid angle of the instrument shows marginal
      variations for varying absorption and backscattering coefficients. Nevertheless,
      the mean centroid angle for the instrument over the entire course of the
      simulation study was found to be 124 degrees  which conforms well with the study
      of Doxaran et al. [Opt. Express 24, 3615 (2016)].

PMID- 30119431
TI  - Low-loss waveguide optical isolator with tapered mode converter and magneto
      optical phase shifter for TE mode input.
AB  - We propose and demonstrate a novel low-loss waveguide optical isolator with
      tapered mode converter and magneto-optical phase shifter. The principle of
      operation of the isolator is based on the superposition of the TE and TM modes.
      The two different modes become direction-dependent due to a magneto-optical phase
      shift affecting the TM mode. We designed a tapered mode converter in order to
      generate the TE and TM modes with equal amplitude when the waveguide is excited
      with a TE mode input. We successfully demonstrated that the fabricated device
      acts as an isolator showing a different transmittance between forward and
      backward directions. The maximum isolation measured is 16 dB at a wavelength of
      1561 nm for a TE mode input.

PMID- 30119432
TI  - Live-cell fluorescence imaging with extreme background suppression by plasmonic
      nanocoatings.
AB  - Fluorescence microscopy allows specific and selective imaging of biological
      samples. Unfortunately, unspecific background due to auto-fluorescence,
      scattering, and non-ideal labeling efficiency often adversely affect imaging.
      Surface plasmon-coupled emission (SPCE) is known to selectively mediate
      fluorescence that spatially originates from regions close to the metal interface.
      However, SPCE combined with fluorescence imaging has not been widely successful
      so far, most likely due to its limited photon yield, which makes it tedious to
      identify the exact window of the application. As the strength of SPCE based
      imaging is its unique sectioning capabilities. We decided to identify its clear
      beneficial operational regime for biological settings by interrogating samples in
      the presence of ascending background levels. For fluorescent beads as well as
      live-cell imaging as examples, we show how to extend the imaging performance in
      extremely high photon background environments. In a common setup using plasmonic
      gold-coated coverslips using an objective-based total internal reflection
      fluorescence microscope (TIRF-M), we theoretically and experimentally
      characterize our fluoplasmonics (f-Pics) approach by providing general user
      guidance in choosing f-Pics over TIRF-M or classical wide-field (WF).

PMID- 30119433
TI  - Accelerated generation of holographic videos of 3-D objects in rotational motion
      using a curved hologram-based rotational-motion compensation method.
AB  - A new curved hologram-based rotational-motion compensation (CH-RMC) method is
      proposed for accelerated generation of holographic videos of 3-D objects moving
      on the random path with many locally different arcs. All of those rotational
      motions of the object made on each arc can be compensated, just by rotating their
      local curved holograms along the curving surfaces matched with the object's
      moving trajectory without any additional calculation process, which results in
      great enhancements of the computational speed of the conventional hologram
      generation algorithms. Experiments with a test video scenario reveal that average
      numbers of calculated object points (ANCOPs) and average calculation times for
      one frame (ACTs) of the CH-RMC-based ray-tracing, wavefront-recording-plane and
      novel- look-up-table methods have been found to be reduced by 73.10%, 73.84%,
      73.34%, and 68.75%, 50.82%, 66.59%, respectively, in comparison with those of
      their original methods. In addition, successful reconstructions of 3-D scenes
      from those holographic videos confirm the feasibility of the proposed system.

PMID- 30119434
TI  - Mechanism of dissipative-soliton-resonance generation in fiber laser mode-locked
      by real saturable absorber.
AB  - Generation of dissipative soliton resonance (DSR) is numerically investigated in
      an all-normal-dispersion Yb-doped fiber laser mode-locked by a real saturable
      absorber (SA). In the simulation model, the SA includes both the saturable
      absorption and reverse saturable absorption (RSA) effects. It is found that the
      RSA effect induced by the SA material itself plays a dominant role in generating
      the DSR pulses. We also systematically analyze the influence of key SA parameters
      on the evolution of DSR pulses in the cavity. Our simulation results not only
      offer insight into the underlying mechanism of DSR generation in mode-locked
      fiber lasers by means of real SAs, but also provide a guideline for engineering
      SA parameters to generate optical pulses with the highest possible energy.

PMID- 30119435
TI  - High efficiency of III-nitride micro-light-emitting diodes by sidewall
      passivation using atomic layer deposition.
AB  - Optoelectronic effects of sidewall passivation on micro-sized light-emitting
      diodes (uLEDs) using atomic-layer deposition (ALD) were investigated. Moreover,
      significant enhancements of the optical and electrical effects by using ALD were
      compared with conventional sidewall passivation method, namely plasma-enhanced
      chemical vapor deposition (PECVD). ALD yielded uniform light emission and the
      lowest amount of leakage current for all uLED sizes. The importance of sidewall
      passivation was also demonstrated by comparing leakage current and external
      quantum efficiency (EQE). The peak EQEs of 20 * 20 um2 uLEDs with ALD sidewall
      passivation and without sidewall passivation were 33% and 24%, respectively. The
      results from ALD sidewall passivation revealed that the size-dependent influences
      on peak EQE can be minimized by proper sidewall treatment.

PMID- 30119436
TI  - Chirped-pulse-amplification seed source through direct phase modulation.
AB  - This work presents integration of a directly chirped laser source (DCLS) into a
      high-energy optical parametric chirped-pulse-amplification (OPCPA) system. DCLS
      is an all-fiber, chirped laser source that produces nanosecond, linearly chirped
      laser pulses at 1053 nm for seeding high-energy chirped-pulse-amplification
      systems. DCLS produces a frequency chirp on an optical pulse through direct
      temporal phase modulation. A 1-ns, linearly chirped pulse with a 3-nm bandwidth
      is produced by applying an ~1000-rad (300pi) quadratic temporal phase. The
      chirped pulse is amplified to 76 mJ in an OPCPA system and compressed to close to
      its Fourier transform limit, producing an intensity autocorrelation trace with a
      1.5-ps width.

PMID- 30119437
TI  - OSNR and nonlinear noise power estimation for optical fiber communication systems
      using LSTM based deep learning technique.
AB  - The optical signal-to-noise ratio (OSNR) and fiber nonlinearity are critical
      factors in evaluating the performance of high-speed optical fiber communication
      systems. Recently, several deep learning based methods have been put forward to
      monitor OSNR of a fiber communication system. In this work, we propose a long
      short-term memory (LSTM) network based method to simultaneously estimate OSNR and
      nonlinear noise power caused by fiber nonlinearity. In the training step, LSTM
      network extracts the essential features in frequency domain of the input signal.
      Then, with the built model in the training step, the LSTM output the OSNR and
      nonlinear noise power of the signal under test. The simulation by VPI software is
      carried on a 5-channel long haul optical transmission system with the launched
      optical power of -3.0~ + 3.0dBm per channel. The results show that the test error
      of OSNR is less than 1.0dB with the reference OSNR from 15 to 30dB for QPSK,
      16QAM and 64QAM signal. The test error of nonlinear noise power is less than
      1.0dB for QPSK and 16QAM signal when the Laser linewidth is 6 KHz and 100 KHz
      respectively. The proposed method is a promising candidate for nonlinearity
      insensitive OSNR and accurate nonlinear noise power estimation in multi-channel
      long haul optical fiber communication systems.

PMID- 30119438
TI  - Picojoule-level octave-spanning supercontinuum generation in chalcogenide
      waveguides.
AB  - Low propagation loss Ge23Sb7S70 waveguides (0.56 dB/cm) are fabricated in a wafer
      scale process. Simulation of a 2 cm long, 1.2 MUm wide waveguide with 100
      ps/nm/km peak dispersion predicts coherent supercontinuum generation at 1.55 MUm
      pump wavelength. Octave-spanning supercontinuum using a dispersive wave is
      experimentally demonstrated using picojoule-level energy (26 pJ, 240 fs pulse
      width, 77 W peak power) pulses.

PMID- 30119439
TI  - Antenna-enhanced high harmonic generation in a wide-bandgap semiconductor ZnO.
AB  - High harmonic generation (HHG) in solids has great potential for coherent extreme
      ultraviolet (EUV) sources, all-optical band-structure reconstruction, and
      electron dynamics metrology. Solid HHG driven by plasmonic near-fields will open
      a new paradigm, enabling high repetition-rate HHG with a compact laser, HHG
      manipulation with meta-surfaces, and precise control over carrier trajectory. In
      this paper, we demonstrate antenna-enhanced HHG in a wide-bandgap semiconductor
      ZnO. By exploiting gold nano-antennas resonating at the driver wavelength of 2
      MUm, we successfully trigger HHG at input intensity of ~0.02 TW/cm2 and observe
      harmonic radiations up to 9th-order. Orders-of-magnitude enhanced conversion
      efficiency at the hot-spots brings about ten-fold enhancement in the total yield.
      The spectral selection rule is found to reflect crystal symmetry, suggesting the
      possibility of nano-scaled EUV sources and band-structure reconstruction.

PMID- 30119440
TI  - Introduction to the Issue on Physics and Applications of Laser Dynamics (IS-PALD
      2017).
AB  - In this paper, we introduce the Optics Express feature issue of the 7th
      International Symposium on Physics and Applications of Laser Dynamics (IS-PALD).
      This issue consists of expanded papers related to oral and poster presentations.
      Selected papers represent the best of IS-PALD 2017.

PMID- 30119441
TI  - Intensity-based adaptive optics with sequential optimization for laser
      communications.
AB  - Wavefront distortions of optical waves propagating through the turbulent
      atmosphere are responsible for phase and amplitude fluctuations, causing random
      fading in the signal coupled into single-mode optical fibers. Wavefront
      aberrations can be confronted, in principle, with adaptive optics technology that
      compensates the incoming optical signal by the phase conjugation principle and
      mitigates the likeliness of fading. However, real-time adaptive optics requires
      phase wavefront measurements, which are generally difficult under typical
      propagation conditions for communication scenarios. As an alternative to the
      conventional adaptive optics approach, here, we discuss a novel phase-retrieval
      technique that indirectly determines the unknown phase wavefront from focal-plane
      intensity measurements. The adaptation approach is based on sequential
      optimization of the speckle pattern in the focal plane and works by iteratively
      updating the phases of individual speckles to maximize the received power. We
      found in our analysis that this technique can compensate the distorted phasefront
      and increase the signal coupled with a significant reduction in the required
      number of iterations, resulting in a loop bandwidth utilization well within the
      capacity of commercially available deformable mirrors.

PMID- 30119443
TI  - Accelerating computation of CGH using symmetric compressed look-up-table in color
      holographic display.
AB  - The huge computational complexity is a challenge for computer-generated hologram
      (CGH) calculation in a holographic display. In this paper, we propose a symmetric
      compressed look-up-table algorithm to accelerate CGH computation based on the
      Fresnel diffraction theory and compressed look-up-table algorithm. In offline
      computation, the memory usage of horizontal and vertical modulation factors is
      reduced to the order of Kilobytes by using translational symmetric compression
      and wavelength separation. In online computation, we develop a one-time
      generation of color holograms method which is accelerated by matrix convolution
      operation. Numerical simulation results show at least 13 times faster than
      existing algorithms without sacrificing the computation precision. The optical
      experiments are performed to demonstrate its feasibility. It is believed that the
      proposed method is an effective algorithm to accelerate the computation of CGH in
      color holographic display.

PMID- 30119442
TI  - Near-infrared optical image transport through an all-solid tellurite optical
      glass rod with transversely-disordered refractive index profile.
AB  - For the first time, an all-solid tellurite optical glass rod with a transversely
      disordered refractive index profile was fabricated successfully as a medium to
      study the transverse localization of light and near-infrared (NIR) optical image
      transport. Two tellurite glass compositions of 70TeO2-8Li2O-17WO3-3MoO3-2Nb2O5
      (TLWMN) and 75TeO2-15ZnO-5Na2O-5La2O3 (TZNL) which have a small difference in
      softening temperature (about 0.5  degrees C), compatible thermal expansions from
      room to 400  degrees C and broad transmission range from about 0.4 up to 6.0 um
      were developed for a successful fabrication process. The tellurite transversely
      disordered optical rod (TDOR) consists of high and low-index units (TLWMN and
      TZNL, respectively). The diameter of each unit is 1.0 MUm and their refractive
      index difference was about 0.095 at 1.55 um. Experimental results showed that
      after a CW probe beam at 1.55 MUm propagated in a 10-cm-long tellurite TDOR, the
      beam became localized. In addition, NIR optical images at 1.55 MUm of numbers on
      a test target were transported. The captured images at the output facet of the
      tellurite TDOR are visually clear with high contrast and high brightness. The
      quality of our transported optical images can be comparable or higher than the
      results which were obtained by a polymer Anderson localized fiber and by a
      commercially available multicore imaging optical fiber.

PMID- 30119445
TI  - Experimental study on polarization evolution locking in a stretched-pulse fiber
      laser.
AB  - Polarization evolution locking (PEL) of a stretched-pulse fiber laser is
      experimentally investigated with a simple pulse selection method based on a fast
      electrooptic modulator, capable of revealing the temporal and spectrum evolution
      of the PEL pulses. Moreover, the wavelength dependence of PEL is observed by
      spectrally filtering the pulses and is further investigated for individual fiber
      laser comb lines through beat note measurements with narrow-linewidth cw lasers.

PMID- 30119444
TI  - 10 W CEP-stable few-cycle source at 2 um with 100 kHz repetition rate.
AB  - We developed a high repetition rate optical parametric chirped-pulse
      amplification (OPCPA) laser system based on fiber-laser-seeded Innoslab to
      generate few-cycle pulses around 2 um with passively stable carrier-envelope
      phase (CEP) by difference frequency generation (DFG). Incorporating a piezo
      mirror before the DFG stage permits rapid CEP control. The OPCPA system is seeded
      by a stable supercontinuum generated in bulk material with the picosecond
      Innoslab pulses. Few-cycle pulses with durations of 17 fs and energies of over
      100 MUJ were produced in a single OPCPA stage. Three different nonlinear
      crystals: BBO, BiBO, and LNB were tested in the final parametric amplifier, and
      their average power related limitations are addressed.

PMID- 30119446
TI  - Two-photon absorption arises from two-dimensional excitons.
AB  - By applying quantum perturbation theory to two-dimensional excitons in monolayer
      transition metal dichalcogenides (TMDCs), we develop a theoretical model for two
      photon absorption in the near infrared spectral region. By assuming the bandwidth
      of the final excitonic state to be 0.15 eV, the two-photon absorption
      coefficients are as high as 50 cm/MW and selenium-based, monolayer TMDCs exhibit
      greater 2PA coefficients than sulfur-based, monolayer TMDCs. Our model is also
      compared to the experimental data obtained by Z-scans or nonlinear transmission
      measurements.

PMID- 30119447
TI  - Feedback-enabled adaptive underwater twisted light transmission link utilizing
      the reflection at the air-water interface.
AB  - Line-of-sight link is widely used in common free-space optical (FSO) laser
      communications between two fixed locations. While in practical underwater
      wireless optical communications (UWOC), the environment is relatively
      complicated. In some scenarios there exist irremovable obstacles, which block the
      line-of-sight optical link. Fortunately, the air-water interface can function as
      a natural mirror to enable non-line-of-sight optical link using the total
      internal reflection. Very recently, twisted light beams carrying orbital angular
      momentum (OAM) have attracted researchers' great attention to improve the
      transmission capacity in UWOC. Here, we propose and experimentally demonstrate a
      non-line-of-sight underwater twisted light transmission link utilizing the total
      internal reflection at the air-water interface. To overcome the beam fluctuation
      and drift caused by the change of interface states, we develop a proof-of-concept
      adaptive feedback system to provide a stable output. Moreover, we study the
      degrading effects of the slight wind effect, the salinity (turbidity) effect, and
      the vertical thermal gradient-induced turbulence effect. The results show that
      the water wave caused by the slight wind causes the most beam drift, the thermal
      gradient causes the most distortions, and the salinity causes the most power
      loss.

PMID- 30119448
TI  - Generation and phase noise analysis of a wide optoelectronic oscillator with
      ultra-high resolution based on stimulated Brillouin scattering.
AB  - Microwave signals with broadband tunable frequencies and low phase noise can be
      widely used in communication systems and radar systems. Optoelectronic
      oscillators (OEOs) with high Q value have the potential to generate the signals
      meeting the above requirements. In this paper, we present a simple scheme to
      realize a widely tunable OEO with ultra-high tuning resolution based on
      stimulated Brillouin scattering (SBS), meanwhile maintaining the low phase noise
      for all the generated frequencies. By choosing different high-order sideband of
      the phase-modulated signal as the SBS pump, the frequency of the generated signal
      can be widely tuned. The accurate frequency tuning can be achieved by changing
      the drive signal frequency of the phase modulator. As a result, the obtained
      signal of the OEO with the frequency tuning range up to 40 GHz, and the tuning
      resolution as accurate as 10 MHz can be obtained. The influence of the SBS gain
      and the drive signal on the signal phase noise is analyzed theoretically. The
      effects of the drive signal and the electrical amplifier on the phase noise of
      the obtained signal are analyzed experimentally. The results show that the noise
      figure of the amplifier directly affects the phase noise quality of the acquired
      signal. And the phase noise of the generated signals is lower than -120 dBc/Hz at
      100 kHz offset frequency, which has no relation with the drive signal, or the
      order of the modulation sideband.

PMID- 30119449
TI  - High sensitivity temperature measurement via mask-free hybrid polymer long period
      fiber grating.
AB  - Long-period fiber gratings (LPFGs) are useful for environmental sensing under
      conditions of high corrosiveness and electromagnetic interference. Most LPFGs are
      fabricated by coherent or high-power UV illumination of an optical fiber under an
      amplitude mask, resulting in narrow and environmentally-dependent band rejection.
      We present a hybrid LPFG waveguide fabricated without an amplitude mask through
      polymer self-assembly under low-power incoherent UV illumination, which
      demonstrates high-temperature sensitivity in its transmission spectrum compared
      to LPFG sensors based purely on silica waveguides. A sensitivity of 1.5 nm 
      degrees C -1 is obtained experimentally for attenuation near 1180 nm, and a
      sensitivity of 4.5 nm  degrees C -1 with a low random error was obtained with a
      composite of attenuation bands. Finite element method simulations and coupling
      mode theory reveal this to be due to a thermo-optic coefficient one order of
      magnitude greater than that of fused silica. The device has potential for a
      simple and inexpensive transmission intensity based temperature sensor consisting
      of an infrared light source, the LPFG, a bandpass filter, and a photodiode.

PMID- 30119450
TI  - High-fidelity distributed fiber-optic acoustic sensor with fading noise
      suppressed and sub-meter spatial resolution.
AB  - In order to solve fading problem and realize sub-meter spatial resolution in DAS,
      this paper proposes a novel configuration of time-gated digital optical frequency
      domain reflectometry (TGD-OFDR) based on optical intensity modulator (IM). IM has
      a large modulation bandwidth and the positive and negative harmonics can be fully
      used to suppress fading while the spatial resolution remains unchanged. In
      experiments, with fading suppressed, the spatial resolution of DAS is 0.8 m and
      the strain resolution is about 245.6 pepsilon?Hz along the total 9.8-km sensing
      fiber. The response bandwidth of vibration is 5 kHz, only/limited by the fiber
      length.

PMID- 30119451
TI  - Multiplexed static FBG strain sensors by dual-comb spectroscopy with a free
      running fiber laser.
AB  - We demonstrate a novel and compact FBG interrogation system for multiplexed
      static strain sensing with a free running mode-locked fiber laser. Multiplexed
      FBG array in cascading are interrogated by coherent dual-comb pulses generated
      from a single fiber laser. Dual-comb spectroscopy is achieved with the fiber
      laser to precisely detect the strain-induced spectral shifts of the FBG sensors.
      Multi-point strain measurements are performed to characterize the proposed
      system, where a large dynamic range of 520 MUepsilon with 0.5 MUepsilon
      resolution is achieved.

PMID- 30119452
TI  - Site symmetry and host sensitization-dependence of Eu3+ real time luminescence in
      tin dioxide nanoparticles.
AB  - The present work gives a detailed investigation of the dependence of the real
      time luminescence of Eu3+-doped tin dioxide nanopowder on rare earth (RE) site
      symmetry and host defects. Ultrafast time-resolved analysis of both RE-doped and
      undoped nanocrystal powder emissions, together with electronic paramagnetic
      resonance studies, show that host-excited RE emission is associated with RE
      induced oxygen vacancies produced by the non-isoelectronic RE-tin site
      substitution that are decoupled from those producing the bandgap excited emission
      of the SnO2 matrix. A lower limit for the host-RE energy transfer rate and a
      model for the excitation mechanism are given.

PMID- 30119453
TI  - Continuous background correction using effective points selected in third-order
      minima segments in low-cost laser-induced breakdown spectroscopy without
      intensified CCD.
AB  - This work presents a method that can automatically estimate and remove varying
      continuous background emission for low-cost laser-induced breakdown spectroscopy
      (LIBS) without intensified CCD. The algorithm finds all third-order minima points
      in spectra and uses these points to partition the spectra into multiple
      subintervals. The mean value is then used as a threshold to select the effective
      points for the second-order minima in each subinterval. Finally, a linear
      interpolation method is used to realize extension of these effective points and
      complete fitting of the background using polynomials. Using simulated and real
      LIBS spectra with different complexities examine the validity of proposed
      algorithm. Additionally, five elements of five standard cast iron alloy samples
      are calibrated and improved very well after background removal. The results
      successfully prove the validity of the background correction algorithm.

PMID- 30119454
TI  - Remote optical sensing in otolaryngology: middle ear effusion detection.
AB  - Otitis Media (OM) is related to a group of inflammatory diseases of the middle
      ear (ME) commonly encountered, worldwide. A method based on a simple device,
      which can be used by medical staff and non-experts to detect OM is presented. The
      method is based on detection of tympanic membrane (TM) vibrations. A laser beam
      is pointed on an infra-sonic stimulated TM with fast camera capturing the back
      scattered secondary speckle patterns. A camera enables inspection of the
      frequency and amplitude of the changes in TM characteristics obtained by analysis
      of the spatial-temporal statistics of the speckle patterns. The results may
      provide information that express ME effusion.

PMID- 30119455
TI  - Monolithically integrated erbium-doped tunable laser on a CMOS-compatible silicon
      photonics platform.
AB  - A tunable laser source is a crucial photonic component for many applications,
      such as spectroscopic measurements, wavelength division multiplexing (WDM),
      frequency-modulated light detection and ranging (LIDAR), and optical coherence
      tomography (OCT). In this article, we demonstrate the first monolithically
      integrated erbium-doped tunable laser on a complementary-metal-oxide
      semiconductor (CMOS)-compatible silicon photonics platform. Erbium-doped Al2O3
      sputtered on top is used as a gain medium to achieve lasing. The laser achieves a
      tunability from 1527 nm to 1573 nm, with a >40 dB side mode suppression ratio
      (SMSR). The wide tuning range (46 nm) is realized with a Vernier cavity, formed
      by two Si3N4 microring resonators. With 107 mW on-chip 980 nm pump power, up to
      1.6 mW output lasing power is obtained with a 2.2% slope efficiency. The maximum
      output power is limited by pump power. Fine tuning of the laser wavelength is
      demonstrated by using the gain cavity phase shifter. Signal response times are
      measured to be around 200 MUs and 35 us for the heaters used to tune the Vernier
      rings and gain cavity longitudinal mode, respectively. The linewidth of the laser
      is 340 kHz, measured via a self-delay heterodyne detection method. Furthermore,
      the laser signal is stabilized by continuous locking to a mode-locked laser (MLL)
      over 4900 seconds with a measured peak-to-peak frequency deviation below 10 Hz.

PMID- 30119456
TI  - Achromatic phase shifting self-interference incoherent digital holography using
      linear polarizer and geometric phase lens.
AB  - A simple Fresnel-type self-interference incoherent digital holographic recording
      system is proposed. The main part of the system consists of the two linear
      polarizers and geometric phase lens. The geometric phase lens is employed as a
      polarization selective common-path interferometer. One of the polarizers is
      rotated by the motor and serves as a phase-shifter with the geometric phase lens,
      to eliminate the bias and twin image noise. A topological phase is obtained by
      the relative angle between the polarizer and geometric phase lens. Since this
      phase shifting method does not depend on the change of the optical path length,
      the phase shifting performance is almost constant in the broad spectral range.
      Using the proposed achromatic phase shifting method, a simultaneous three-color
      phase shifting digital hologram recording under the incoherent light source is
      demonstrated.

PMID- 30119457
TI  - Solid-state 589 nm seed laser based on Raman fiber amplifier for sodium
      wind/temperature lidar in Tibet, China.
AB  - A narrowband sodium lidar for measuring mesospheric temperature and wind has been
      established at YangBaJing, Tibet (90 degrees E, 30 degrees N, 4300 m a.s.l),
      China. The system is designed and optimized based on important upgrades using new
      technology. In the lidar system, single-mode 589 nm seed laser is produced by
      frequency doubling of 1178 nm diode laser with a periodically poled lithium
      niobate (PPLN) waveguide. The output power of 589 nm continuous-wave laser is up
      to 1.5 W with the help of a seed-injected Raman fiber amplifier. Furthermore,
      fast three-frequency switcher is designed with a couple of fiber magneto optical
      switches (FMOS) for measuring wind and temperature, simultaneously, which greatly
      reduces the system maintenance. These improvements greatly simplify the lidar
      system, thus, achieve robust operation with minimum maintenance requirements.

PMID- 30119458
TI  - Numerical method for vesicle movement analysis in a complex cytoskeleton network.
AB  - The detection of the precise movement of a vesicle during transport in a live
      cell provides key information for the intracellular delivery process. Here we
      report a novel numerical method for analyzing three-dimensional vesicle movement.
      Since the vesicle moves along a linear cytoskeleton during the active transport,
      our method first detects the orientation and position of the cytoskeleton as a
      linear section based on angle correlation and linear regression, after noise
      reduction. Then, the precise vesicle movement is calculated using vector
      analysis, in terms of rotation angle and translational displacement. Using this
      method, various vesicle trajectories obtained via high spatiotemporal resolution
      microscopy can be understood..

PMID- 30119460
TI  - Broadband birefringent metamaterial lens with bi-functional high-gain radiation
      and deflection properties.
AB  - Birefringent metamaterial shows fantastic properties in controlling the
      propagation of electromagnetic wave. Based on the birefringent theory, a Ku-band
      birefringent metamaterial lens is proposed, which can radiate high gain TE wave
      with a TE wave feed and deflect incident TM wave. To realize bi-functional high
      gain radiation or deflection, the required permittivity distribution is analyzed
      first. Then, the unit cells of metamaterial lens are carefully designed based on
      effective permittivity equations to achieve the desired permittivity
      distribution. To demonstrate the present design, a cylindrical birefringent lens
      prototype is fabricated using 3D printing techniques. The experiments verify
      that, with a rectangular waveguide feeding on the lens surface or a horn antenna
      illuminated in the far field, the Ku-band birefringent metamaterial lens performs
      as a high-gain broadband radiator for the TE wave feed or a deflector for the
      incident TM wave.

PMID- 30119459
TI  - Controllable photonic and phononic edge localization via optomechanically induced
      Kitaev phase.
AB  - Experimental realization of the Kitaev model is a greatly attractive topic due to
      the potential applications to build robust qubits against decoherence in
      topological quantum computation. In this work, we investigate the charged
      whispering-gallery microcavity array model and simulate the normal Kitaev chain
      under this mechanism in the first time. We find that the system reveals profound
      connections with the normal Kitaev chain and its some derivatives, and the
      topological property of the system depends on effective optomechanical coupling
      strength deeply. In optomechanically induced Kitaev topologically nontrivial
      phase, compared to the normal Kitaev chain in the Majorana basis, the novel and
      distinct structure of charged whispering-gallery microcavity array model leads to
      controllable photonic and phononic edge localization. Furthermore, we also
      simulate the extended Kitaev chain and show that two topologically different
      nontrivial phases of the system allow one to realize more freewheeling
      controllable photonic and phononic edge localization. Our model offers an
      alternative approach to correlate with other more complicated one-dimensional
      noninteracting spinless topological systems relevant to the p-wave
      superconducting pairing.

PMID- 30119461
TI  - Correction of projector nonlinearity in multi-frequency phase-shifting fringe
      projection profilometry.
AB  - In fringe projection profilometry, the original purpose of projecting multi
      frequency fringe patterns is to determine fringe orders automatically, thus
      unwrapping the measured phase maps. This paper presents that using the same
      patterns, simultaneously, allows us to correct the effects of projector
      nonlinearity on the measured results. As is well known, the projector
      nonlinearity decreases the measurement accuracies by inducing ripple-like
      artifacts on the measured phase maps; and, theoretical analysis reveals that
      these artifacts, depending on the number of phase shifts, have multiplied
      frequencies higher than the fringe frequencies. Based on this fact, we deduce an
      error function for modeling the phase artifacts and then suggest an algorithm
      estimating the function coefficients from a couple of phase maps of fringe
      patterns having different frequencies. As a result, subtracting out the estimated
      phase errors yields the accurate phase maps with the effects of the projector
      nonlinearity on them being suppressed significantly. Experiment results
      demonstrated that this proposed method offers some advantages over others, such
      as working without a photometric calibration, being applicable when the projector
      nonlinearity varies over time, and having satisfied efficiency in implementation.

PMID- 30119462
TI  - Maximal quantum Fisher information for phase estimation without initial parity.
AB  - Mach-Zehnder interferometer is a common device in quantum phase estimation and
      the photon losses in it are an important issue for achieving a high phase
      accuracy. Here we thoroughly discuss the precision limit of the phase in the Mach
      Zehnder interferometer with a coherent state and a superposition of coherent
      states as input states. By providing a general analytical expression of quantum
      Fisher information, the phase-matching condition and optimal initial parity are
      given. Especially, in the photon loss scenario, the sensitivity behaviors are
      analyzed and specific strategies are provided to restore the phase accuracies for
      symmetric and asymmetric losses.

PMID- 30119463
TI  - Dual-mode DFB laser diodes with apodized surface gratings.
AB  - Dual longitudinal mode distributed feedback lasers have been fabricated using
      surface gratings with and without apodization. Analytic formulas and simulations
      that have been used to derive design guidelines are presented. The fabricated
      device characteristics are in good agreement with the simulations. The grating
      apodization enables a lower threshold current density, a higher output power and
      a broader range of difference frequency tunability by bias, which can be extended
      beyond the measured 15-55 GHz by changing the device structure. The apodization
      and the complex coupling of the surface gratings reduce the effects of the
      uncontrollable phase of facet reflections, enabling the use of higher facet
      reflectivities, which leads to narrower intrinsic short time-scale linewidths.

PMID- 30119464
TI  - Dispersion engineered high quality lithium niobate microring resonators.
AB  - Lithium niobate (LN) exhibits outstanding material properties with great
      potential for many applications. Recent advance in LN integrated photonics on
      chip-scale platforms has shown significant advantages in device engineering and
      functionality innovation. Precise engineering of group-velocity dispersion (GVD)
      is crucial for many important nonlinear photonic applications. In this paper, we
      demonstrate high-Q LN microring resonators, with optical Q above 1 million, whose
      GVD can be flexibly controlled in both normal and anomalous dispersion regimes,
      with a value between -0.128 ps2/m and 0.043 ps2/m in the telecom band, by
      controlling the device cross section and by utilizing the birefringence. We are
      able to achieve a small anomalous GVD of -0.015 ps2/m that is even smaller than
      that of a silica optical fiber. The flexible engineering of GVD paves a critical
      step towards broad nonlinear photonic applications in high-Q LN microring
      resonators.

PMID- 30119465
TI  - Polymer waveguide WDM channel selector operating over the entire C and L bands.
AB  - A tunable channel selector operating over both the C and L bands of wavelength
      division-multiplexing optical network is proposed based on a thermo-optic tunable
      Bragg grating device in a polymer waveguide. A tilted Bragg grating cascaded with
      an asymmetric Y-branch waveguide effectively implements a small Bragg-reflection
      wavelength filter that does not require an external circulator. To increase the
      operating wavelength span of the channel selector, two Bragg gratings with
      different periods are fabricated on a single substrate for covering C and L
      bands, respectively. A wide tuning range over 80 nm along with a narrow bandwidth
      is demonstrated. Moreover, the polarization dependence of the reflection spectrum
      is observed to be less than 0.1 nm.

PMID- 30119466
TI  - Propagation properties of Hermite non-uniformly correlated beams in turbulence.
AB  - We study the propagation properties (intensity, degree of coherence and
      scintillation) of a new class of beams in a turbulent atmosphere, which are
      called Hermite non-uniformly correlated (HNUC) beams. The results show that the
      beams not only have lower scintillation but also higher intensity than Gaussian
      Schell model (GSM) beams over certain propagation ranges. We can adjust the beam
      order of HNUC beams to enhance the intensity of the beam in the receiver plane
      and, simultaneously, reduce the detrimental scintillation, and we can also adjust
      the coherence length of HNUC beams to optimize the effects of a given propagation
      distance between a signal transmitter and a receiver.

PMID- 30119467
TI  - 3D polymer directional coupler for on-board optical interconnects at 1550 nm.
AB  - We propose three-dimensional (3D) polymer directional couplers operating at 1550
      nm for on-board optical interconnects. The proposed directional coupler can
      realize free-position light coupling and splitting in three dimension and can be
      cascaded to serve as an effective and scalable device for multi-layer and multi
      channel interconnects. The 3D directional coupler was fabricated with
      commercially available UV-curable epoxies by combining the use of a needle-type
      liquid micro-dispenser and a 3-axis robot stage. The main parameters of the 3D
      directional coupler such as the interaction length, coupling ratio, coupling
      position, and cascade numbers can be easily adjusted. In the experiment, single
      mode two-dimensional (2D) polymer directional couplers in both horizontal and
      vertical directions operating at 1550 nm with different coupling ratios (CRs)
      were demonstrated at first. The experimental results agree with the simulated
      ones. A 3D directional coupler with coupling ratios of 58:23:19 at 1550 nm was
      then successfully fabricated using the mosquito method for the first time to the
      best of our knowledge. The CR varies with the wavelength as expected while the
      excess loss remains almost the same within C-band. The results imply that the
      proposed method may be applicable in the fabrication of functional devices in
      three dimension for high-density on-board optical interconnects with further
      improvement on fabrication process.

PMID- 30119468
TI  - Emission enhancement in dielectric nanocomposites.
AB  - We consider emitting nanoparticles in dielectric nanocomposites with varying
      refractive index contrast and geometry. For that we develop a simple and
      universal method to calculate the emission enhancement in nanocomposites that
      employs solely the calculation of the effective refractive index and electric
      field distributions from three quasistatic calculations with orthogonal
      polarizations. The method is exemplified for dilute nanocomposites without
      electromagnetic interaction between emitting particles as well as for dense
      nanocomposites with strong particle interaction. We show that the radiative decay
      in dielectric nanocomposites is greatly affected by the shape and arrangement of
      its constituents and give guidelines for larger enhancement.

PMID- 30119469
TI  - Modes, stability, and small-signal response of photonic crystal Fano lasers.
AB  - Photonic crystal Fano lasers have recently been realised experimentally, showing
      useful properties such as pinned single-mode lasing and passive pulse generation.
      Here the fundamental properties of the modes of the Fano laser are analysed,
      showing how the laser functionality depends sensitively on the system
      configuration. Furthermore the laser stability is investigated and linked to the
      small-signal response, which shows additional dynamics that cannot be explained
      with a conventional rate equation model, including a damping of relaxation
      oscillations and a frequency modulation bandwidth that is only limited by the
      nanocavity response.

PMID- 30119470
TI  - Parameter-retrieval of dry-air wake vortices with a scanning Doppler Lidar.
AB  - A wake vortex is a form of irregular airflow generated by a flying aircraft,
      which can cause a severe hazard for aviation. To quantify the hazard of a wake
      after fully roll-up and before rebound, this paper proposes an algorithm to
      retrieve its characteristic parameters (circulations, vortex-core positions, and
      vortex-core radii) with a scanning Doppler Lidar. In the algorithm, a governing
      equation related to the Doppler velocities and characteristic parameters is
      established based on the aerosols' weak inertia, from which the target parameters
      are solved with an optimization method. During the process, the distortion of
      Doppler velocity caused by the scanning of the Lidar beam is adjusted by the
      Doppler acceleration to achieve better estimations of the target characteristic
      parameters. Good performance of the algorithm has been verified by simulation and
      field detection data.

PMID- 30119471
TI  - Nonlinear impairment scaling with the number of mode groups in mode-multiplexed
      transmission over a 50 um multimode fiber.
AB  - We numerically investigate the impact of nonlinear effects in mode-multiplexed
      transmission over a 50 um graded-index multimode fiber. Such a fiber supports 36
      spatial modes, well suited for a mode-multiplexed transmission. The number of
      mode groups used for transmission is subsequently increased to identify the
      nonlinear penalty occurring due to the Kerr-effect-based nonlinear interaction
      between the spatial modes. It is shown that the nonlinear penalty scales less
      than proportional with the number of modes and hence, is no obstacle for using
      such a fiber for a mode-multiplexed transmission. Consequently, we clarify the
      potential to upgrade the transmission capacity over time with such a fiber.

PMID- 30119472
TI  - Iodine-stabilized high resolution dual-frequency Ti: sapphire laser.
AB  - A dual frequency Ti: sapphire laser is presented in which two lines operate
      simultaneously with the same intensity on two TM00 longitudinal modes. This
      operation is obtained by means of the 127I2 molecules contained in an intra
      cavity cell, pumped by a low-power laser. Its properties are interesting: the two
      lines lase simultaneously, they overlap spatially, their spectral width could be
      very narrow, their frequency is automatically locked to molecular frequencies and
      can serve as a frequency reference, the frequency difference is adjustable over
      the thousands of rotational or vibrational molecular energy gaps in the 0.1-0.9
      THz and 3-6 THz domains, and it is computable with high precision. THz wave
      production is demonstrated as a first application.

PMID- 30119473
TI  - High-repetition-rate ultrafast fiber lasers.
AB  - Multi-gigahertz fundamental repetition rate, tunable repetition rate and
      wavelength, ultrafast fiber lasers at wavelengths of 1.0, 1.5, and 2.0 um are
      experimentally demonstrated and summarized. At the wavelength of 1.0 um, the
      laser wavelength is tuned in the range of 1040.1-1042.9 nm and the repetition
      rate is shifted by 226 kHz in a 3-cm-long all-fiber laser by controlling the
      temperature of the resonator. Compared with a previous work where the maximum
      average power was 0.8 mW, the power in this study is significantly improved to 57
      mW under a launched pump power of 213 mW, thus achieving an optical-to-optical
      efficiency of 27%. For comparison, a similar temperature-tuning technique is
      implemented in a Tm3+-doped ultrafast oscillator but, as expected, it results in
      a broader tunable range of 14.1 nm (1974.1-1988.2 nm) in wavelength as compared
      with the value of 1.8 nm for the wavelength of 1.0 um. The repetition rate in the
      process is shifted by 294 kHz. For the high-frequency range from 100 kHz to 10
      MHz, the value of integrated timing jitter gradually increases with an increase
      in temperature. Finally, to the best of our knowledge, for the first time, a new
      method for tuning wavelength and repetition rate is proposed and demonstrated for
      a femtosecond fiber laser at the wavelength of 1.5 um. Through fine rotation of
      the alignment angle between the Er/Yb:glass fiber and a semiconductor saturable
      absorption mirror, the peak wavelength can be tuned in the range of 1591.4-1586.1
      nm and the repetition rate is shifted by 60 kHz.

PMID- 30119474
TI  - Shared secret key generation from signal fading in a turbulent optical wireless
      channel using common-transverse-spatial-mode coupling.
AB  - Common randomness arising from turbulence-induced signal fading in reciprocal
      optical wireless channels is a beneficial resource that can be used to generate
      secret keys shared by two legitimate parties. The concept of optical wireless
      channels using common-transverse-spatial-mode coupling (CTSMC) that can maintain
      perfect fading reciprocity in atmospheric turbulence is first developed in a
      general manner. Subsequently, by performing Monte Carlo simulations, the Johnson
      SB probability distribution is demonstrated to be appropriate for statistical
      description of turbulence-induced signal fading in an optical wireless channel
      constructed by use of two identical CTSMC transceivers, and the nature of
      correlation between signal fadings detected by two contiguous reception spatial
      modes is further quantitatively characterized, revealing that rapid spatial
      decorrelation between signal fadings observed by a legitimate party and an
      eavesdropper holds for scenarios of practical interest. Finally, the information
      theoretic capacity for generating secret keys from CTSMC-based optical wireless
      channels is theoretically formulated and quantitatively examined under different
      conditions, manifesting that the turbulence strength and average electrical
      signal-to-noise ratio have a noticeable combined impact on the secret key
      capacity, especially in the far-field case.

PMID- 30119475
TI  - Phosphor modeling based on fluorescent radiative transfer equation.
AB  - The behaviors of the light propagation in the phosphor play a vital role in
      determining the optical performance of the phosphor-converted light-emitting
      diodes (pc-LEDs). In this paper, we presented a general model based on the
      radiative transfer equation integrated with fluorescence (FRTE) to describe the
      overall light propagating properties in the phosphor layer in terms of light
      absorption, strong forward scattering, and fluorescence. The model was
      established by accounting for general boundary conditions including the LED
      Lambertian incidence, the diffuse reflection at the substrate/reflector, and the
      Fresnel reflection at the phosphor-air interface. The spectral element method
      (SEM) was extended to numerically solve FRTE. The radiant intensity at any
      location and direction of blue and yellow light was iteratively calculated, in
      which case the angular properties could be further evaluated. The model was
      validated by comparing the light extraction efficiency (LEE) and angular
      correlated color temperature (CCT) calculated by the presented model with the
      experimental results. Good agreements were achieved between model predictions and
      measurements with the corresponding maximum deviation of 4.9% and 3.7% for LEE
      and CCT, respectively. We also conducted a comparison between our model and the
      previous Kubelka-Munk (KM) theory. It has been revealed that the KM theory may
      overestimate the phosphor heating due to lacking of the blue light scattering
      effect.

PMID- 30119476
TI  - Intense laser filament-solid interactions from near-ultraviolet to mid-infrared.
AB  - Studies of high-power ultrashort laser pulse interaction with matter are not only
      of fundamental scientific interest, but are also highly relevant to applications
      in the domain of remote sensing. Here, we investigate the effect of laser
      wavelength on coupling of femtosecond laser filaments to solid targets. Three
      central wavelengths have been used to produce filaments: 0.4, 0.8, and 2.0 um. We
      find that, unlike the case of conventional tight focusing, use of shorter
      wavelengths does not necessarily produce more efficient ablation. This is
      explained by increased multi-photon absorption arising in near-UV filamentation.
      Investigations of filament-induced plasma dynamics and its thermodynamic
      parameters provide the foundation for unveiling the interplay between wavelength
      dependent filament ablation mechanisms. In this way, strategies to increase the
      sensitivity of material detection via this technique may be better understood,
      thereby improving the analytical performance in this class of applications.

PMID- 30119478
TI  - Influences of high-order dispersion on temporal and spectral properties of
      microcavity solitons.
AB  - We theoretically and numerically investigate the effects of high-order dispersion
      (HOD) on microcavity solitons, both in time and frequency domain with an extended
      normalized Lugiato-Lefever equation (LLE). The observed temporal drift of bright
      and dark solitons is shown to originate from high-odd-order dispersion, while the
      sign determines the direction of soliton movement and the amplitude decides the
      drift speed. HOD can also be introduced to stabilize the breathing bright and
      dark cavity solitons. In spectral domain, the nonlinear symmetry breaking is
      mainly introduced by third-order dispersion, whereas both third- and fourth-order
      dispersion can introduce dispersive wave accompanied by soliton tail oscillation.
      This work could give insight for exploring detailed intracavity pulse dynamics
      and spectral characteristics of Kerr combs influenced by HOD, as well as provide
      a viable route to delicate control of Kerr comb generation through tailoring the
      dispersion parameters.

PMID- 30119477
TI  - Transparent transmission-selective radar-infrared bi-stealth structure.
AB  - We report a multifunctional metamaterial composite structure that not only
      provides the broadband radar and thermal infrared bi-stealth function but also
      possesses an in-band microwave transmission window and high optical transparency.
      It is composed of four metasurface layers made of indium tin oxide (ITO) films
      with different surface resistances, which are specifically designed to
      sequentially control the infrared emission, microwave absorption and
      transmission. The fabricated sample exhibits a low reflectivity less than 10% in
      1.5-9 GHz and a transmission peak of 50% around 3.8 GHz up to the incident angle
      of 30 degrees. In the infrared atmosphere window, a low thermal emissivity of
      about 0.52 is achieved. Meanwhile, it keeps good optical transparency by the use
      of the ITO films. The optically transparent, low-infrared-emissivity, radar
      reflectionless and frequency-selective-transmission properties will enable the
      promising application of communication-compatible multispectral stealth
      technology.

PMID- 30119479
TI  - Removal of reflections in LWIR image with polarization characteristics.
AB  - Long-wave infrared (LWIR) imaging has been successfully used in surveillance
      applications in low illumination conditions. However, infrared energy reflected
      from smooth surfaces such as floors and metallic objects may reduce object
      detection and tracking accuracies. In this paper, we present a novel reflection
      removal method using polarization properties of the reflection in LWIR imagery.
      Reflection can be distinguished from the scene by two unique characteristics of
      polarization: the difference of two orthogonal polarized components (OPC) and the
      uniformity of angle of polarization (AoP). The OPC difference helps locate the
      regions of reflection. The uniformity of AoP in the reflection region pose a
      strong constraint for reflection detection. The proposed joint reflection
      detection method combines the OPC difference and the uniformity of AoP can detect
      actual reflection region. Then the closed-form matting method improves the
      robustness of the method and removes the reflection from the scene. Experiment
      results demonstrate that the proposed scheme effectively removes the reflection
      in challenging situations where many existing techniques may fail.

PMID- 30119480
TI  - Design rules for optimizing unipolar coded Brillouin optical time-domain
      analyzers.
AB  - The performance of unipolar unicolor coded Brillouin optical time-domain analysis
      (BOTDA) is evaluated based on both Simplex and Golay codes. Four major
      detrimental factors that limit the system performance, including decoded-gain
      trace distortion, coding pulse power non-uniformity, polarization pulling and
      higher-order non-local effects, are thoroughly investigated. Through theoretical
      analysis and an experimental validations, solutions and optimal design conditions
      for unipolar unicolor coded BOTDA are clearly established. First, a logarithmic
      normalization approach is proposed to resolve the linear accumulated Brillouin
      amplification without distortion. Then it is found out that Simplex codes are
      more robust to pulse power non-uniformity compared to Golay codes; whilst the use
      of a polarization scrambler must be preferred in comparison to a polarization
      switch to mitigate uncompensated fading induced by polarization pulling in the
      decoded traces. These optimal conditions enables the sensing performance only
      limited by higher-order non-local effects. To secure systematic errors below 1.3
      MHz on the Brillouin frequency estimation, while simultaneously reaching the
      maximum signal-to-noise ratio (SNR), a mathematical model is established to trade
      off the key parameters in the design, i.e., the single-pulse Brillouin
      amplification, code length and probe power. It turns out that the optimal SNR
      performance depends in inverse proportion on the value of maximum single-pulse
      Brillouin amplification, which is ultimately determined by the spatial
      resolution. The analysis here presented is expected to serve as a quantitative
      guideline to design a distortion-free coded BOTDA system operating at maximum
      SNR.

PMID- 30119481
TI  - Orbital-angular-momentum-enhanced estimation of sub-Heisenberg-limited angular
      displacement with two-mode squeezed vacuum and parity detection.
AB  - We report on an orbital-angular-momentum-enhanced scheme for angular displacement
      estimation based on two-mode squeezed vacuum and parity detection. The sub
      Heisenberg-limited sensitivity for angular displacement estimation is obtained in
      an ideal situation. Several realistic factors are also considered, including
      photon loss, dark counts, response-time delay, and thermal photon noise. Our
      results indicate that the effects of realistic factors on the sensitivity can be
      offset by raising orbital angular momentum quantum number l. This implies that
      the robustness and the practicability of the system can be improved via raising l
      without changing mean photon number N.

PMID- 30119482
TI  - Dark solitons manipulation using optical event horizon.
AB  - We demonstrate that the optical event horizon can provide an effective technique
      to actively control the propagation properties of a dark soliton with another
      weak probe wave. Careful power adjustment of the probe wave enables the black
      soliton converted into a gray one with varying grayness through the nonlinear
      interaction, corresponding to a nearly adiabatic variation of the soliton's
      speed. The sign of the phase angle for the newly formed gray soliton at optical
      event horizon is significantly dependent on the frequency of the launched probe
      wave. Linear-stability analysis of dark solitons under the perturbation of a weak
      probe wave is performed to clarify the intrinsic mechanism of the nonlinear
      interaction. The probe wave manipulated collisional dynamics between both dark
      solitons are investigated as an analogue of the combined white-hole and black
      hole horizons which provides some insights into exploring the transition between
      integrable and non-integrable systems.

PMID- 30119483
TI  - Computational-weighted Fourier single-pixel imaging via binary illumination.
AB  - Single-pixel imaging has the ability to generate images at nonvisible wavelengths
      and under low light conditions and thus has received increasing attention in
      recent years. Fourier single-pixel imaging (FSI) utilizes deterministic basis
      patterns for illumination to greatly improve the quality of image reconstruction.
      However, the original FSI based on grayscale Fourier basis illumination patterns
      is limited by the imaging speed as the digital micro-mirror devices (DMD) used to
      generate grayscale patterns operate at a low refresh rate. In this paper, a new
      approach is proposed to increase the imaging speed of DMD-based FSI without
      reducing the imaging spatial resolution. In this strategy, the grayscale Fourier
      basis patterns are split into a pair of grayscale patterns based on
      positive/negative pixel values, which are then decomposed into a cluster of
      binary basis patterns based on the principle of decimalization to binary. These
      binary patterns are used to illuminate the imaged object. The resulting detected
      light intensities multiply the corresponding weighted decomposed coefficients and
      are summed, and the results can be used to generate the Fourier spectrum for the
      imaged object. Finally, an inverse Fourier transform is applied to the Fourier
      spectrum to obtain the object image. The proposed technique is verified by a
      computational simulation and laboratory experiments. Both static and dynamic
      imaging experiments are carried out to demonstrate the proposed strategy. 128 *
      128 pixels dynamic scenes at a speed of ~9 frames-per-second are captured under
      22 KHz projection rate using a DMD. The reported technique accelerates the
      imaging speed for DMD-based FSI and provides an alternative approach to improve
      FSI efficiency.

PMID- 30119484
TI  - Applicability of the effective medium approximation in the ellipsometry of
      randomly micro-rough solid surfaces.
AB  - The effective medium approximation (EMA) has been widely applied to model the
      effect of a solid sample with surface roughness in spectroscopic ellipsometry
      (SE). There are two specific cases to utilize the EMA model. One is utilizing the
      EMA model to perform the inversion of the optical constants of solid samples from
      the SE measurements. Another is utilizing the EMA model to estimate the thickness
      of the rough layer at solid surface from the SE measurements under the condition
      in which the optical constants of samples are known. For the first case, the
      thickness of the rough layer is usually assumed to be the root mean square (rms)
      roughness as measured by atomic force microscopy (AFM). We theoretically
      investigate the error of the EMA model to estimate optical constants for
      different surface morphologies and materials. Because the EMA model only accounts
      for the height irregularities of rough surfaces but neglects the effect of the
      lateral irregularities on electromagnetic scattering from rough surfaces, it is
      difficult to obtain high-precision results for optical constants. Moreover, the
      inversion error of optical constants by using the EMA model is difficult to
      evaluate. In the second case, the thickness of the rough layer is estimated by
      using the EMA model from the SE measurements, called the EMA model roughness. We
      show that the EMA model roughness generally has a deviation from the rms
      roughness as measured by AFM. Some correlated relationships are established
      between the EMA model roughness and the morphological parameters of rough
      surfaces. It is found that these relationships have similar forms but not
      identical coefficients for different materials. The results from this work may
      facilitate a better understanding and utilization for the EMA model in SE.

PMID- 30119485
TI  - High dynamic range liquid crystal displays with a mini-LED backlight.
AB  - We analyze the performance of high dynamic range liquid crystal displays (LCDs)
      using a two-dimensional local dimming mini-LED backlight. The halo effect of such
      a HDR display system is investigated by both numerical simulation and human
      visual perception experiment. The halo effect is mainly governed by two factors:
      intrinsic LCD contrast ratio (CR) and dimming zone number. Based on our results,
      to suppress the halo effect to indistinguishable level, a LCD with CR~5000:1
      requires about 200 local dimming zones, while for a LCD with CR~2000:1 the
      required dimming zone number is over 3000. Our model provides useful guidelines
      to optimize the mini-LED backlit LCDs for achieving dynamic contrast ratio
      comparable to organic LED displays.

PMID- 30119486
TI  - Optimization-free approach for generating sub-diffraction quasi-non-diffracting
      beams.
AB  - Sub-diffraction quasi-non-diffracting beams with sub-wavelength transverse size
      are attractive for applications such as optical nano-manipulation, optical nano
      fabrication, optical high-density storage, and optical super-resolution
      microscopy. In this paper, we proposed an optimization-free design approach and
      demonstrated the possibility of generating sub-diffraction quasi-non-diffracting
      beams with sub-wavelength size for different polarizations by a binary-phase
      Fresnel planar lens. More importantly, the optimization-free method significantly
      simplifies the design procedure and the generation of sub-diffracting quasi-non
      diffracting beams. Utilizing the concept of normalized angular spectrum
      compression, for wavelength lambda0 = 632.8 nm, a binary-phase Fresnel planar
      lens was designed and fabricated. The experimental results show that the sub
      diffraction transverse size and the non-diffracting propagation distances are
      0.40lambda0-0.54lambda0 and 90lambda0, 0.43lambda0-0.54lambda0 and 73lambda0, and
      0.34lambda0-0.41lambda0 and 80lambda0 for the generated quasi-non-diffracting
      beams with circular, longitudinal, and azimuthal polarizations, respectively.

PMID- 30119487
TI  - Prospects for 100% wall-plug efficient III-nitride LEDs.
AB  - The possibility of a III-nitride LED with 100% or greater wall-plug efficiency is
      examined considering recent observations of the phenomenon for smaller bandgap
      mid-IR LEDs under extremely low-bias operation [Phys. Rev. Lett. 108, 1 (2012)].
      Thermoelectric pumping of carriers by lattice heat enables >= 100% WPE, but this
      effect is relatively weaker for the wider band gap III-nitrides. This work
      assesses the electrical and optical performance of several state-of-the-art
      nitride devices and summarizes the requirements and prospects for approaching >=
      100% WPE for III-nitride LEDs operating at technologically relevant current
      densities (> 1 A/cm2).

PMID- 30119488
TI  - Calibration sample for arbitrary metrological characteristics of optical
      topography measuring instruments.
AB  - Areal optical surface topography measurement is an emerging technology for
      industrial quality control. However, neither calibration procedures nor the
      utilization of material measures are standardized. State of the art is the
      calibration of a set of metrological characteristics with multiple calibration
      samples (material measures). Here, we propose a new calibration sample (artefact)
      capable of providing the entire set of relevant metrological characteristics
      within only one single sample. Our calibration artefact features multiple
      material measures and is manufactured with two-photon laser lithography (direct
      laser writing, DLW). This enables a holistic calibration of areal topography
      measuring instruments with only one series of measurements and without changing
      the sample.

PMID- 30119490
TI  - Evaluation of the robustness of polarization attraction for 10.7-GBaud NRZ-BPSK
      after long-haul 100-GHz DWDM transmission.
AB  - An investigation was carried out on the polarization attraction (PA) of a
      polarization-scrambled 10.7-GBaud NRZ-BPSK signal in a 1-km-long highly nonlinear
      fiber (HNLF). For the back-to-back case, PA on an ASE-loaded signal yielded a
      receiver sensitivity penalty of ~ 14.5 dB at the ITU-T G.975.1.I3 FEC threshold
      of 3.5 * 10-3, relative to matched-filter reception theory. After long-haul 100
      GHz DWDM transmission in a recirculating loop, PA on the output signal was found
      to achieve approximately the same receiver sensitivity performance, as that of
      the back-to-back case. From these experiments, it is concluded that the Gordon
      Mollenauer effect due to propagation in the HNLF during PA dominates other
      impairments including those arising from the long-haul 100-GHz DWDM recirculating
      loop transmission.

PMID- 30119489
TI  - Mapping the dynamical regimes of a SESAM mode-locked VECSEL with a long cavity
      using time series analysis.
AB  - The different dynamical regions of an optically-pumped SESAM mode-locked, long
      cavity VECSEL system with a fundamental pulse repetition frequency of ~200 MHz
      are investigated. The output power, captured as 250 MUs long time series using a
      sampling rate of 200 GSa/s, for each operating condition of the system, is
      analyzed to determine the dynamical state. A wavelength range of 985-995 nm and
      optical pump powers of 10 W-16.3 W is studied. The system produces high quality
      fundamental passive mode-locking (FML) over an extensive part of the parameter
      space, but the different dynamical regions outside of FML are the primary focus
      of this study. We report five types of output: CW emission, FML, mode-locking of
      a few modes, double pulsing, and, semi-stable 4th harmonic mode-locking. The high
      sampling rate of the oscilloscope, combined with the long duration of the time
      series analyzed, enables insight into how the structure and substructure of
      pulses vary systematically over thousands of round trips of the laser cavity.
      Higher average output power is obtained in regions characterized by semi-stable
      4th harmonic mode-locking than observed for FML, raising whether such average
      powers might be achieved for FML. The observed dynamic transitions from
      fundamental mode-locking provide insights into instability challenges in
      developing a stable, widely tunable, low repetition rate, turn-key system; and to
      inform future modelling of the system.

PMID- 30119491
TI  - Passively Q switched dual channel Tm:YLF laser by intracavity spectral beam
      combination with volume Bragg gratings.
AB  - A novel dual channel Tm:YLF laser system was developed where two degenerate laser
      cavities were coupled by spectrally beam combining their emission and by
      implementing a common output coupler. Under continuous wave running conditions,
      each channel's slope efficiency was greater than 45% and the maximum combined
      output power was 11 W. Passive Q-switching was achieved using an 80%, Cr:ZnSe
      saturable absorber. The output pulses had a maximum energy of 5.8 mJ and duration
      of 90 ns (~65 kW of peak power) at 5.7 W of absorbed pump power. Each channel
      showed less than 1 nm of spectral width with central wavelengths around 1880 nm
      and 1908 nm correspondingly. The system had adjustable spectral difference
      between the channels ranging from 5 to 20 nm which corresponds to 0.4 - 1.7 THz
      if the system is used for nonlinear difference frequency generation.

PMID- 30119492
TI  - High accuracy transfer printing of single-mode membrane silicon photonic devices.
AB  - A transfer printing (TP) method is presented for the micro-assembly of integrated
      photonic devices from suspended membrane components. Ultra thin membranes with
      thickness of 150nm are directly printed without the use of mechanical support and
      adhesion layers. By using a correlation alignment scheme vertical integration of
      single-mode silicon waveguides is achieved with an average placement accuracy of
      100+/-70nm. Silicon (Si) MU-ring resonators are also fabricated and show
      controllable optical coupling by varying the lateral absolute position to an
      underlying Si bus waveguide.

PMID- 30119493
TI  - High-gain erbium silicate waveguide amplifier and a low-threshold, high
      efficiency laser.
AB  - Erbium-doped materials have played an important role in the fabrication of light
      sources used in silicon photonics. Recent studies demonstrated that erbium
      silicate nanowire had a high net gain attributable to its high erbium
      concentration and excellent material quality. We establish a more accurate and
      comprehensive theoretical model of erbium silicate nanowire, analyze the modeled
      nanowire's properties, and optimize a high-gain erbium silicate waveguide
      amplifier and low-threshold, high-efficiency laser by considering upconversion,
      energy transfer, and amplified spontaneous emission. The simulation results and
      previous experimental data reported in reference showed some agreement. A
      proposed waveguide amplifier, based on the optimized design, displayed a gain
      greater than 20 dB/mm. Then, a 3.3 mW low-threshold laser with a maximum power
      conversion efficiency of 50% was modeled by choosing the optimized resonator
      cavity and reflector. The results indicate that erbium silicate compound
      materials with large optical gains can serve as potential candidates for
      inclusion in scale-integrated amplifiers and other applications requiring lasers.

PMID- 30119494
TI  - Self-calibrated microscopic dual-view tomographic holography for 3D flow
      measurements.
AB  - This paper introduces the application of microscopic dual-view tomographic
      holography (M-DTH) to measure the 3D position and motion of micro-particles
      located in dense suspensions. Pairing of elongated traces of the same particle in
      the two inclined reconstructed fields requires precise matching of the entire
      sample volume that accounts for the inherent distortions in each view. It is
      achieved by an iterative volumetric self-calibration method, consisting of
      mapping one view onto the next, dividing the sample volume into slabs, and cross
      correlating the two views. Testing of the procedures using synthetic particle
      fields with imposed distortion and realistic errors in particle locations shows
      that the self-calibration method achieves a 3D uncertainty of about 1um, a third
      of the particle diameter. Multiplying the corrected intensity fields is used for
      truncating the elongated traces, whose centers are located within 1um of the
      exact value. Without correction, only a small fraction of the traces even
      overlap. The distortion correction also increases the number of intersecting
      traces in experimental data along with their intensity. Application of this
      method for 3D velocity measurements is based on the centroids of the
      truncated/shortened particle traces. Matching of these traces in successive
      fields is guided by several criteria, including results of volumetric cross
      correlation of the multiplied intensity fields. The resulting 3D velocity
      distribution is substantially more divergence-free, i.e., satisfies conservation
      of mass, compared to analysis performed using single-view data. Sample
      application of the new method shows the 3D flow structure around a pair of cubic
      roughness elements embedded in the inner part of a high Reynolds number turbulent
      boundary layer.

PMID- 30119495
TI  - High precision calibration of optical lattice depth based on multiple pulses
      Kapitza-Dirac diffraction.
AB  - The precise calibration of optical lattice depth is an important step in the
      experiments of ultracold atoms in optical lattices. The Raman-Nath diffraction
      method, as the most commonly used method of calibrating optical lattice depth,
      has a limited range of validity and the calibration accuracy is not high enough.
      Based on multiple pulses Kapitza-Dirac diffraction, we propose and demonstrate a
      new calibration method by measuring the fully transfer fidelity of the first
      diffraction order. The high sensitivity of the transfer fidelity to the lattice
      depth ensures the highly precision calibration of the optical lattice depth. For
      each lattice depth measured, the calibration uncertainty is further reduced to
      less than 0.6% by applying the Back-Propagation Neural Network Algorithm. The
      accuracy of this method is almost one order of magnitude higher than that of the
      Raman-Nath diffraction method, and it has a wide range of validity applicable to
      both shallow lattices and deep lattices.

PMID- 30119496
TI  - Information theoretical approaches in computational lithography.
AB  - Computational lithography is nowadays playing an indispensible role in improving
      the imaging performance of optical lithography systems. This paper develops a new
      and powerful approach to computational lithography by introducing an information
      theoretical channel modeling in partially coherent lithography systems. A
      statistical model is built up based on the lithography imaging model to
      characterize the information transfer between the mask and print images. Then,
      this paper calculates the optimal information transfer (OIT) in partially
      coherent lithography systems, and derives the theoretical limit of image fidelity
      for optical proximity correction (OPC), which is used extensively in
      computational lithography. Finally, the proposed information theoretical
      approaches are applied to improve the OPC solutions obtained by the gradient
      based algorithm. A set of simulations are provided to verify the proposed
      information theoretical model and approaches.

PMID- 30119497
TI  - Quantitative region-of-interest tomography using variable field of view.
AB  - In X-ray computed tomography, the task of imaging only a local region of interest
      (ROI) inside a larger sample is very important. However, without a priori
      information, this ROI cannot be exactly reconstructed using only the image data
      limited to the ROI. We propose here an approach of region-of-interest tomography,
      which reconstructs a ROI within an object from projections of different fields of
      view acquired on a specific angular sampling scheme in the same tomographic
      experiment. We present a stable procedure that not only yields high-quality
      images of the ROI but keeps as well the quantitative contrast on the
      reconstructed images. In addition, we analyze the minimum number of projections
      required for ROI tomography from the point of view of the band region of the
      Radon transform, which confirms this number must be estimated based on the size
      of the entire object and not only on the size of the ROI.

PMID- 30119498
TI  - Tailoring optical responses of infrared plasmonic metamaterial absorbers by
      optical phonons.
AB  - Here we numerically and experimentally explore the rich phenomena in the optical
      responses and local electromagnetic fields of a MIM absorber mediated by the
      dispersive spacer. We first show that the line shape of the spectral absorption
      is strongly modified by the interaction between the plasmonic resonances and the
      optical phonons in the silicon dioxide spacer. Importantly, broadening the
      spectral absorption in the long wave infrared range is achieved by tuning the
      strength of coupling. Modification to the local electromagnetic field
      distribution in the epsilon-near-zero region is also numerically studied. The
      incident-angle dependence and polarization dependence of the broadened absorption
      spectrum are evaluated. We also show that the spectral broadening mechanism can
      be generalized to other frequency bands by employing different spacing materials
      such as silicon nitride and polydimethylsiloxane. Our results can be useful for
      designing spectrally selective thermal detectors and thermal emitters.

PMID- 30119499
TI  - Inverse method to engineer uniform-intensity focal fields with arbitrary shape.
AB  - We present an inverse method to engineer uniform-intensity focal fields with
      arbitrary shape. Amplitude, phase, and polarization states, as adjustable
      parameters, are used to seek the desired focal fields in the non-iterative
      computational procedure. Our method can be applied to the cases with low and
      moderate numerical aperture (NA), in which case the feasibility and validity of
      our approach have been demonstrated in theory, simulation and experiment,
      respectively. For the case of higher NA, simulated results based on the Richards
      Wolf diffraction integral are shown. We also made some discussions on the
      experiments with the higher NA. Our method should have wide applications in
      optical micro machining, optical trapping and so on.

PMID- 30119500
TI  - Microscale local strain gauges based on visible micro-disk lasers embedded in a
      flexible substrate.
AB  - Microscale local strain gauges with low-power consumption and large strain range
      were demonstrated by integrating microdisk lasers in a deformable and flexible
      polymer substrate. The lasing spectra of microdisk lasers were sensitive to
      substrate deformation and can be modulated by strains. The measured relative
      wavelength tuning under strains of the novel strain sensors illustrated a linear
      behavior with the gauge factor being ~4.0 nm and ~6.7 nm per stretching unit for
      microdisk lasers with the diameter of 1.2 MUm and 1.5 MUm, which corresponding to
      a smooth wavelength tuning of 1.5 nm and 2.6 nm under 36% strain, respectively.
      In addition, to being used as microscale strain gauges, the visible lasers on the
      deformable substrate can also function as a tunable light source for the photonic
      integrated circuits and flexible laser projection displays.

PMID- 30119501
TI  - Ultra-high-image-density large-size organic light-emitting devices based on In-Ga
      Zn-O thin-film transistors with a coplanar structure.
AB  - Drain currents as functions of the gate voltages for the thin-film transistors
      (TFTs) showed that their output currents had slight differential variations in
      the saturation region just as the output currents of the etch stopper TFTs did.
      The maximum difference in the threshold voltages for the In-Ga-Zn-O (a-IGZO) TFTs
      was as small as approximately 0.57 V. The color gamut of organic light-emitting
      devices (OLEDs) embedded with TFTs with a coplanar structure satisfied the
      digital cinema initiatives of 99%. Furthermore, the image density of large-size
      OLEDs embedded with TFTs with a coplanar structure was significantly enhanced in
      comparison with that of OLEDs embedded with conventional TFTs.

PMID- 30119502
TI  - Digital correction method for realizing a phase-stable dual-comb interferometer.
AB  - A phase-stable dual-comb interferometer measures materials' broadband optical
      response functions, including amplitude, frequency, and phase, making it a
      powerful tool for optical metrology. Normally, the phase-stable dual-comb
      interferometer is realized via tight phase-locking methods. This paper presents a
      post-correction algorithm that can compensate for carrier wave phase noise and
      interferogram timing jitter. The compensating signal is a beat between two combs
      using a free-running continuous wave laser as an optical intermediary. In our
      experiment, sub-hertz relative linewidth, ~1 ns relative timing jitter, and 0.2
      rad precision in the carrier phase is demonstrated.

PMID- 30119503
TI  - Dynamic control of transverse magnetization spot arrays.
AB  - We propose a feasible strategy for firstly constructing diffraction-limited light
      induced magnetization spot arrays capable of dynamically controlling transverse
      polarization orientation of each spot. To achieve this goal, we subtly design a
      tailored incident light comprised of two sorts of beams and sufficiently
      demonstrate tit's production through phase modulation of a radially polarized
      beam. Via tightly focusing counter-propagating composite illuminating beams in a
      4pi optical microscopic configuration, two orthogonally polarized focal fields
      with pi/2 phase difference between them are formed, inducing a three-dimensional
      (3D) super-resolved transverse magnetization spot in the magnetic-optical (MO)
      film. Exploiting the ideal of the multi-zone plate (MZP) filter, we further
      achieve versatile magnetization spot arrays with controllable in-plane
      polarization direction in each spot. Such well-defined magnetization behavior is
      attributed to not merely the coherent interference of vectorial optical waves,
      but also non-overlapping superposition of localized focal fields. Our achievable
      outcomes pave the way for practical applications in spintronics and multi-value
      MO parallelized storage.

PMID- 30119504
TI  - Approximation and blind reconstruction of volumetric light field.
AB  - Recovering the real light field, including the light field intensity
      distributions and continuous volumetric data in the object space, is an
      attractive and important topic with the developments in light-field imaging. In
      this paper, a blind light field reconstruction method is proposed to recover the
      intensity distributions and continuous volumetric data without the assistant of
      prior geometric information. The light field reconstruction problem is
      approximated to be a summation of the localized reconstructions based on image
      formation analysis. Blind volumetric information derivation is proposed based on
      backward image formation modeling to exploit the correspondence among the
      deconvoluted results. Finally, a light field is blindly reconstructed via the
      proposed inverse image formation approximation and wave propagation. We
      demonstrate that the method can blindly recover the light field intensity with
      continuous volumetric data. It can be further extended to other light field
      imaging systems if the backward image formation model can be derived.

PMID- 30119505
TI  - Accelerated synthesis of wide-viewing angle polygon computer-generated holograms
      using the interocular affine similarity of three-dimensional scenes.
AB  - The interocular affine similarity of three-dimensional scenes is investigated and
      a novel accelerated reconfiguration algorithm for intermediate-view polygon
      computer-generated holograms based on interocular affine similarity is proposed.
      We demonstrate by using the numerical simulations of full-color polygon computer
      generation holograms that the proposed intermediate view reconfiguration
      algorithm is particularly useful for the computation of wide-viewing angle
      polygon computer-generated holograms.

PMID- 30119506
TI  - Finite element steady periodic beam propagation analysis of mode instability in
      high power fiber amplifiers.
AB  - A finite element steady periodic scalar beam propagation method suited to
      treating mode instability in amplifiers incorporating fibers with complicated
      design features is presented and demonstrated on test cases. These incorporate
      large pitch photonic crystal fibers with confined and down-doped cores in co
      pumped and counter-pumped configurations. Seed power fluctuations and slight
      launch misalignment are proposed and implemented as a noise source to seed the
      instability. Down doping the confined core by -7.0E-5 was found to increase the
      instability threshold by 25% in the co-pumped case and 9% in the counter-pumped
      case. The increase in threshold is correlated with the suppression of higher
      frequency components of intensity gratings associated with the instability.

PMID- 30119507
TI  - Fano resonance in double waveguides with graphene for ultrasensitive biosensor.
AB  - Fano resonance is realized in the multilayer structure consisting of two planar
      waveguides (PWGs) and few layer graphene, and the coupling mechanism between the
      two PWG modes with graphene is analyzed in detail. It is revealed that the Fano
      resonance originates from the different quality factors due to the different
      intrinsic losses of the graphene in the two waveguides, and the electric field
      distributions in the multilayer structure confirms our results. Fano resonance in
      our proposed structures can be applied in the ultrasensitive biosensor, and a
      significantly improved figure of merit (FOM) of 9340 RIU-1 has been obtained by
      optimizing the structure parameters, which has a 2~3 orders of magnitude
      enhancement compared to the traditional surface plasmon polaritons (SPR) sensor.
      Especially, it is found that both transverse magnetic (TM)-polarization and
      transverse electric (TE)-polarization can support the Fano resonance, and hence
      it can work as ultrasensitive biosensor for both polarizations.

PMID- 30119508
TI  - Photothermal generation of programmable microbubble array on nanoporous gold
      disks.
AB  - We present a novel technique to generate microbubbles photothermally by
      continuous-wave laser irradiation of nanoporous gold disk (NPGD) array covered
      microfluidic channels. When a single laser spot is focused on the NPGDs, a
      microbubble can be generated with controlled size by adjusting the laser power.
      The dynamics of both bubble growth and shrinkage are studied. Using computer
      generated holography on a spatial light modulator (SLM), simultaneous generation
      of multiple microbubbles at arbitrary locations with independent control is
      demonstrated. A potential application of flow manipulation is demonstrated using
      a microfluidic X-shaped junction. The advantages of this technique are flexible
      bubble generation locations, long bubble lifetimes, no need for light-adsorbing
      dyes, high controllability over bubble size, and relatively lower power
      consumption.

PMID- 30119509
TI  - Graphene-assisted multilayer structure employing hybrid surface plasmon and
      magnetic plasmon for surface-enhanced vibrational spectroscopy.
AB  - A graphene-assisted vertical multilayer structure is proposed for high
      performance surface-enhanced Raman scattering (SERS) and surface-enhanced
      infrared absorption (SEIRA) spectroscopies on a single substrate, employing
      simultaneous localized surface plasmon in the visible region and magnetic plasmon
      resonance in the mid-infrared region. Such multilayer structure consists of a
      monolayer graphene sandwiched between Ag nanoparticles (NPs) and a metal
      insulator-metal (MIM) microstructure, which can be easily fabricated by a
      standard surface micromachining process. Benefiting from the large near field
      enhancement by the hybrid plasmons in both visible and mid-infrared regions, a
      high enhancement factor of up to 107 for SERS and 105 for SEIRA can be achieved.
      Additionally, the strong magnetic resonance of the MIM microstructure can be
      tuned in broadband to selectively enhance the desired vibration modes of
      molecules. The strong SERS and SEIRA enhancement together with easy fabrication
      provides new opportunities for developing integrated plasmonic devices for
      multispectral detection of molecules on the same substrate.

PMID- 30119511
TI  - Accelerating convergence of an iterative solution of finite difference frequency
      domain problems via schur complement domain decomposition.
AB  - We show that iterative solution of Maxwell's equations using the finite
      difference frequency-domain method can be significantly accelerated by using a
      Schur complement domain decomposition method. We account for the improvement by
      analyzing the spectral properties of the linear systems resulting from the use of
      the domain decomposition method.

PMID- 30119510
TI  - Sustained oscillations accompanying polarization switching in laser dynamics.
AB  - We report experimentally and theoretically the emergence of sustained
      oscillations over a slow and periodic polarization switching in a laser subjected
      to polarization rotated optical feedback. This phenomenon originates from a clear
      bifurcation point that marks the transition between sustained and damped
      oscillations on the plateaus. Analytical study reveals also that the frequency of
      this new oscillatory dynamics is independent of the time delay.

PMID- 30119512
TI  - Tunable, omnidirectional, and nearly perfect resonant absorptions by a graphene
      hBN-based hole array metamaterial.
AB  - In this paper, we propose an electrically tunable mid-infrared plasmonic-phononic
      absorber with omnidirectional and polarization insensitive nearly perfect
      resonant absorption characteristics. The absorber consists of a
      graphene/hexagonal boron nitride (hBN)/graphene multilayer on top of a gold
      bottom reflector separated by a dielectric spacer. The graphene/hBN/graphene
      multilayer is patterned as a hole array in square lattice. We analytically and
      numerically prove that, due to the support of hybrid plasmon-phonon-polaritons,
      nearly perfect multi-resonant absorption peaks with high quality factors are
      obtained both inside and outside of the Reststrahlen band of hBN. As a result of
      the hybridization of graphene plasmons with the hyperbolic phonon polaritons of
      hBN, the high quality resonant absorptions of the metamaterial are almost
      unaffected by decreasing the phenomenological electron relaxation time of
      graphene. Moreover, the obtained resonances can be effectively tuned in practice
      due to the continuity of the graphene layers in the hole array metamaterial.
      These features make the graphene-hBN metamaterial a skeptical design for
      practical purposes and mid-infrared multi-functional operations such as sensing.

PMID- 30119513
TI  - Enhanced high-harmonic generation up to the soft X-ray region driven by mid
      infrared pulses mixed with their third harmonic.
AB  - We systematically study the efficiency enhancement of high-harmonic generation
      (HHG) in an Ar gas cell up to the soft X-ray (SXR) range using a two-color laser
      field composed of 2.1 MUm (omega) and 700 nm (3omega) with parallel linear
      polarization. Our experiment follows the recent theoretical investigations that
      determined two-color mid-infrared (IR) pulses, mixed with their third harmonic
      (omega + 3omega), to be close to optimal driving waveforms for enhancing HHG
      efficiency in the SXR region [Jin et al., Nature Comm. 5, 4003 (2014)]. We
      observed sub-optical-cycle-dependent efficiency enhancements of up to 8.2 of
      photon flux integrated between 20 - 70 eV, and up to 2.2 between 85 - 205 eV.
      Enhancement of HHG efficiency was most pronounced for the lowest tested backing
      pressure (~ 140 mbar), and decreased monotonically as the pressure was increased.
      The single-color (omega)-driven HHG was optimal at the highest backing pressure
      tested in the experiment (~ 375 mbar). Our numerical simulations based on single
      atom response and 3D pulse propagation show good qualitative agreement with
      experimental observations. The lower enhancement at high pressure and higher
      photon energy indicates that phase matching of two-color-driven HHG is more
      sensitive to ionization rate and pulse propagation effects than the single-color
      case. We show that with further improvements to the relative phase jitter and the
      spatio-temporal overlap of the two beams, the efficiency enhancement could be
      further improved by at least a factor of ~ 2.

PMID- 30119514
TI  - Design of an optofluidic diffusion sensor by transient grating using
      dielectrophoresis.
AB  - An optofluidic diffusion sensor using laser-induced dielectrophoresis in a device
      with a sputtered a-Si:H layer is presented. Diffusion sensors enabling high-speed
      measurement have important potential uses as bio-sensors and for quantitative
      analysis of nano-sized products. The present sensor was developed for measurement
      in a few seconds by optic observations of the sample diffusion from transient
      grating formed by laser-induced dielectrophoresis. As a photoconductive layer for
      the proposed device, we used a sputtered a-Si:H film. The optical (refractive
      index and extinction coefficient), structural (Raman and IR spectroscopy), and
      optoelectronic properties of this film, as well as its applicability to the
      proposed device are characterized. Nano-sized beads were measured by the
      fabricated device, and its performance as a diffusion sensor was validated.

PMID- 30119515
TI  - Simulation and application of the emission line O19P18 of O2(a1Deltag) dayglow
      near 1.27 MUm for wind observations from limb-viewing satellites.
AB  - The O2(a1Deltag) emission near 1.27 MUm has relatively bright signal and extended
      altitude coverage and provides an important means to remotely sense the
      compositional structures and dynamical features of the upper atmosphere globally.
      In this paper, we report the simulation and application of O2(a1Deltag) dayglow
      near 1.27 MUm for wind observations from limb-viewing satellites. A line by line
      radiative transfer model of the O2(aDelta1g,upsilon'=0)->O2(XSigma3g,upsilon"=0)
      band is developed by taking both multiple scattering radiative transfer and
      nonlocal thermal equilibrium (non-LTE) models into account. The emission line
      O19P18 (7772.030 cm-1) with weak self-absorption, bright radiation intensity, and
      large spectral separation range is proved to be suitable for limb-viewing wind
      detection, due to its advantages of significantly lower cost, risk, and platform
      requirements. In order to ascertain the wind precision of O19P18, observations by
      a DASH-type (the Doppler asymmetric spatial heterodyne) instrument are simulated.
      The simulated results indicate a wind measurement precision of 1-2 m/s over an
      altitude range of 40 to 70 km in general, and possibly to 2-4 m/s due to a strong
      dependence on the spectral interference of the scattered sunlight background.

PMID- 30119516
TI  - Stable actively Q-switched single-frequency fiber laser at 1.5 MUm based on self
      injecting polarization modulation.
AB  - A new technique for the realization of a stable Q-switched operation in a single
      frequency fiber laser based on self-injecting polarization modulation is
      demonstrated, for the first time to the best of our knowledge. A piezoelectric
      fiber stretcher was utilized to introduce periodic stress-induced polarization
      changes. Then the modulation of polarization state transformed into Q switching
      by virtue of a designed distributed Bragg reflector (DBR) resonant cavity with
      polarizations loss anisotropy. Finally, a stable actively Q-switched single
      frequency fiber laser at 1.5 MUm with Gaussian-shape pulse output was achieved.
      We experimentally found that, the repetition frequency (several hundred kHz)
      coincided with the working frequency of the polarization modulation, and the
      pulse width (several hundred ns) reduced with the increasing of the modulating
      frequency, the modulating amplitude, as well as the pump power. This stable Q
      switched single-frequency fiber laser is promising for applications in optical
      time-domain reflectometry, coherent Doppler wind radar, and optical coherent
      detection. More importantly, this novel Q-switched technology may be applicable
      to other DBR single-frequency fiber lasers.

PMID- 30119517
TI  - Selective variable optical attenuator for visible and mid-Infrared wavelengths.
AB  - This work demonstrates a variable optical attenuator (VOA) using dynamic
      scattering mode (DSM) in ion-doped liquid crystals with negative dielectric
      anisotropy. The mechanism of attenuation comes from optical scattering, which is
      generated by the electrically induced instability of undulation of LC textures.
      Electric fields are applied to switch the initial transparent state of the
      designed VOA to scattering states, varying the transmittance. The electric field
      also changes the size of the scattering domain from the LC texture and causes the
      designed device to exhibit an ultra-broadband selective operation in a visible to
      mid-IR spectral range. Furthermore, the VOA can selectively block one visible or
      mid-IR wavelength of light while letting other light pass. Such a VOA has many
      superior optical switching properties, such as high on/off contrast,
      insensitivity to polarization, and spectral selectivity; therefore, it has the
      potential to be used in practical optical systems.

PMID- 30119518
TI  - Single-channel 200 Gbit/s, 10 Gsymbol/s-1024 QAM injection-locked coherent
      transmission over 160 km with a pilot-assisted adaptive equalizer.
AB  - We demonstrate a 10 Gsymbol/s, 1024 quadrature amplitude modulation (QAM) 160 km
      coherent transmission with an injection locking technique. Our newly developed,
      pilot-assisted adaptive equalizer has greatly improved the precision of waveform
      distortion compensation, and this has enabled us to increase the symbol rate to
      10 Gsymbol/s in a 1024 QAM transmission. Thus, we could realize a 200 Gbit/s,
      1024 QAM transmission over 160 km with a potential spectral efficiency of 12.6
      bit/s/Hz.

PMID- 30119519
TI  - Single-walled carbon nanotubes assisted THz silicon grating modulator.
AB  - Single-walled carbon nanotubes (SWCNTs) are applied to realize an enhanced
      frequency modulation for a suspended THz silicon grating, which is fabricated by
      a nanosecond laser direct writing and coated with the synthetic
      SWCNTs/polyacrylic emulsion composite. With terahertz time domain spectroscopy
      system, the transmission spectra of the bare and SWCNTs coated silicon grating
      are measured and compared. The SWCNTs coated silicon grating can realize an
      improved extinction ratio and quality factor, which is due to the SWCNTs caused
      local field enhancement and can be explained by the theoretical simulation with
      finite element method. Besides the effective modulation of the grating
      transmittance, SWCNTs can also be integrated with other platforms and applied in
      future THz imaging and communication systems.

PMID- 30119520
TI  - Pr:RbPb2Cl5: temperature dependent spectra, dynamics and three-for-one
      excitation: erratum.
AB  - We present an erratum regarding the contents of Table 1.

PMID- 30119521
TI  - Yb-doped large mode area fiber for beam quality improvement using local adiabatic
      tapers with reduced dopant diffusion.
AB  - A newly designed all-solid step-index Yb-doped aluminosilicate large mode area
      fiber for achieving high peak power at near diffraction limited beam quality with
      local adiabatic tapering is presented. The 45um diameter fiber core and pump
      cladding consist of active/passively doped aluminosilicate glass produced by
      powder sinter technology (REPUSIL). A deliberate combination of innovative
      cladding and core materials was aspired to achieve low processing temperature
      reducing dopant diffusion during fiber fabrication, tapering and splicing. By
      developing a short adiabatic taper, robust seed coupling is achieved by using
      this Yb-doped LMA fiber as final stage of a nanosecond fiber Master Oscillator
      Power Amplifier (MOPA) system while maintaining near diffraction limited beam
      quality by preferential excitation of the fundamental mode. After application of
      a fiber-based endcap, the peak power could be scaled up to 375 kW with high beam
      quality and a measured M2 value of 1.3~1.7.

PMID- 30119522
TI  - Point-ahead demonstration of a transmitting antenna for satellite quantum
      communication.
AB  - A low-divergence beam is an essential prerequisite for a high-efficiency long
      distance optical link, particularly for satellite-based quantum communication. A
      point-ahead angle, caused by satellite motion, is always several times larger
      than the divergence angle of the signal beam. We design a novel transmitting
      antenna with a point-ahead function, and provide an easy-to-perform calibration
      method with an accuracy better than 0.2 MUrad. Subsequently, our antenna
      establishes an uplink to the quantum satellite, Micius, with a link loss of 41-52
      dB over a distance of 500-1,400 km. The results clearly confirm the validity of
      our model, and provide the ability to conduct quantum communications. Our
      approach can be adopted in various free space optical communication systems
      between moving platforms.

PMID- 30119523
TI  - Terahertz rare-earth orthoferrite metamaterials by 3-D direct writing technology.
AB  - Terahertz (THz) radiation excites electronic and optical modes of many materials,
      and controlling interaction of these materials with THz pulses provides a
      fascinating avenue to achieve unprecedented functionalities in return. Here,
      woodpile-structured rare-earth orthoferrite metamaterials built with 3-D direct
      ink writing technology are proposed and experimentally demonstrated. Polarization
      independent THz refraction and switching of resonances by varying the number of
      layers in the structure, as well as the structural parameters and specimen
      support angle are achieved. Such all-rare-earth-orthoferrite dielectric
      metamaterials are easy to fabricate and can be very promising in developing
      efficient and low cost THz functional metadevices.

PMID- 30119525
TI  - In situ measurement of micro flow rate using near infrared absorption method.
AB  - A novel technique is presented for measuring micro flow rate using the near
      infrared (NIR) absorption method. The principle of this method is based on the
      temperature dependency of the NIR absorption band of water (O-H band, nu1 + nu3).
      We obtained the water temperature in the tube in situ condition using NIR
      absorption method. A calibration curve between temperature and the NIR absorption
      intensity in the range of 1500 nm - 1700 nm wavelength was obtained. For
      measuring flow rate in the tube, the tiny spot of water in the tube was heated
      using NIR laser (1450 nm) through the lens which was absorbed into the water. The
      temperature profiles along the tube were obtained using the NIR absorption method
      via laser heating for different flow rates. The simulation results of the
      temperature profiles were well matched with the experimental results of it for
      different flow rates. We found that the conduction affected the temperature more
      when the flow was low in the upstream and the convection more affected when the
      flow rate was high in the downstream through the heat transfer analysis. The flow
      rates were obtained from the temperature difference between the room temperature
      and the obtained temperature from the NIR method. The calibration curves between
      the flow rate and temperature obtained from the NIR absorption method was
      obtained in the two flow rates (1-20 mL/h and 40-100 mL/h). The error and
      uncertainty of the NIR absorption method for measuring flow rate were
      approximately 1.2% and 1% at the 1-100 mL/min flow rate, respectively. Thus, we
      confirmed that the NIR absorption method quantitatively measures the flow rate
      with respect to the in situ condition for the first time. This method is used for
      various applications including biomedical and chemical processing without causing
      any contamination owing to the flow meter installation.

PMID- 30119524
TI  - Arbitrary multiple beam forming by two cascaded liquid crystal optical phased
      arrays.
AB  - A new method for non-mechanical laser beam splitting and steering is
      demonstrated. Two cascaded liquid crystal optical phased arrays (LC-OPAs)
      controllably modulate the amplitude and phase of an incident laser beam to
      realize the near-field wavefronts of multiple simultaneous beams with arbitrary
      directions. Diffraction between the two arrays is avoided by precise 4-f imaging
      from one LC-OPA to the other (array resolution 1*1920). In the method of cascaded
      amplitude and phase (CAP) devices, numerical simulation results show the
      characteristics of amplitude and phase modulation profiles, as well as the far
      field intensity patterns. Both the numerical and experimental results clearly
      demonstrate the capabilities of fast multi-beam forming with high efficiency
      (>85%, 4 beams) and accuracy (deviation <90MUrad).

PMID- 30119526
TI  - Responsivity improvement of Ti-diamond-Ti structured UV photodetector through
      photocurrent gain.
AB  - In this study, a Ti-diamond-Ti structured ultraviolet photodetector was
      fabricated on a homoepitaxial diamond layer with an oxygen-terminated surface.
      The properties of the Ti/diamond schottky contact were measured using X-ray
      photoelectron spectroscopy, and the barrier height was found to be 1.15 eV. At a
      bias of 3 V, the responsivity at 210 nm was only 4.29 mA/W, while at 12 V, the
      responsivity increased rapidly to 51 mA/W. The increase can be ascribed to the
      photocurrent gain. With the further increase in voltage, an avalanche effect was
      produced, and the responsivity could reach 1.18 A/W at 50 V. Moreover, the
      transient response behavior of the photodetector exhibited a good repeatability
      and response speed.

PMID- 30119527
TI  - Developing a generalized BRDF model from experimental data.
AB  - In this paper, we present a model for BRDF that can be developed from a limited
      set of experimentally observed data, and which then can be used for predictive
      purposes in scene-generation or sensor-performance applications. The model is
      physics based and can be as detailed as desired, depending on the scope of
      experimental data available. Basic input parameters required are the complex
      refractive index of the material, or the directional hemispherical reflectivity
      (DHR) for s- and p-polarized radiation. At least one BRDF measurement is needed
      to determine the angular spread function. Incorporating BRDF measurements at
      several angles of incidence into the model yields better accuracy for describing
      behavior such as forward scatter, depolarization, the participation of volumetric
      and surface-scattering mechanisms in layered surfaces, diffuse-scatter coherence
      properties, and narrowing of the angular spread function which provides an
      indication of optical depth. Illustrations and demonstrations of the methodology
      are drawn from data sets measured on bead-blasted aluminum, automotive paint
      incorporating a clear-coat layer, and green low-gloss vehicle paint.

PMID- 30119528
TI  - General theory of asymmetrical polarization-dependent optics in functional
      material-doped 90 degrees  twisted nematic liquid crystals.
AB  - General theory, which can completely describe the asymmetrical optics in a
      functional material (FM)-doped 90 degrees  twisted nematic liquid crystals
      (TNLCs), is proposed using Cayley-Hamilton theorem and Jones calculus. The FMs,
      whose shape and size are similar to those of the adopted NLCs, can be aligned
      along the long axes of the NLCs. The FMs discussed herein are dichroic dye (DD)
      and polymer. The experimental results of asymmetrical transmission in DD-doped 90
      degrees  TNLCs are consistent with the theoretical calculation. Such asymmetrical
      characterization can be further used in the current applications based on 90
      degrees  TNLCs in all fields to obtain new potential functions.

PMID- 30119529
TI  - Quadrichromatic LED based mobile phone camera visible light communication.
AB  - A quadrichromatic light-emitting diode (QLED) based visible light communication
      for mobile phone camera is proposed to improve data rate and enhance illumination
      effect at the same time. Different from color intensity modulation (CIM), we
      propose and use color ratio modulation (CRM) in CMOS image sensor based visible
      light communication to improve data rate. According to the spectral power
      distribution (SPD) of the QLED and the spectral response of the complementary
      metal-oxide-semiconductor (CMOS) image sensor, color multiple-input multiple
      output (CMIMO) channel model is set up first to obtain optimal 16-CRM
      constellation design. Taking full consideration of the high quality of color
      rendering index (CRI), tunable color temperature (CT), we design a specific data
      packet structure to realize illumination requirements. A decoding strategy is
      also addressed for demapping at the receiver. The experimental results
      demonstrate that the proposed scheme can realize a downlink data rate of
      13.2kbit/s, meanwhile, the optical signal source is illumination compatible.

PMID- 30119530
TI  - Shape-preserving and unidirectional frequency conversion by four-wave mixing.
AB  - In this work, we investigate the properties of four-wave mixing Bragg scattering
      driven by orthogonally polarized pumps in a birefringent waveguide. This
      configuration enables a large signal conversion bandwidth, and allows strongly
      unidirectional frequency conversion as undesired Bragg-scattering processes are
      suppressed by waveguide birefringence. Moreover, we show that this form of Bragg
      scattering preserves the (arbitrary) signal pulse shape, even when driven by
      pulsed pumps.

PMID- 30119531
TI  - Collective matrix of spatial light modulators for increased resolution in
      holographic image projection.
AB  - We present a method to increase the resolution of holographically projected
      images by the use of a collective matrix of two phase-only spatial light
      modulators. As a result of fine alignment and common coherent illumination of the
      modulators, a synthetic aperture is formed with a doubled number of active
      pixels. In this paper we present theoretical analysis and numerical simulations
      which stand in good agreement for different distances between the apertures of
      modulators. We have achieved experimentally controlled field interference from
      both modulators on the projection screen, exhibiting increased resolution in one
      spatial direction and residual effects of the dead space between modulators. Then
      we have proved numerically possibility to extend our approach on bigger synthetic
      apertures consisted of more than two modulators.

PMID- 30119532
TI  - Hybrid multi-layer displays providing accommodation cues.
AB  - Hybrid multi-layer displays are proposed as the system combines additive light
      field (LF) displays and multiplicative LF displays. The system is implemented by
      integrating the multiplicative LF displays with a half mirror to expand the
      overall depth of field. The hybrid displays are advantageous in that the form
      factor is competitive with existing additive LF displays with 2 layers
      implemented by a half mirror and two panels, only half of brightness loss is
      experienced compared to multiplicative LF displays with 2 layers, and no time
      division is required to provide images for multi-layer displays. The images for
      presentation planes are processed by light field factorization and optimized with
      the presented algorithm. Retinal images are reconstructed based on various
      accommodation states and display types to check the accommodation response and
      utilized to compare the proposed displays with existing displays. With ray
      tracing method, retinal images generated by the proposed displays can be
      obtained. To verify the feasibility of the system, a prototype of hybrid multi
      layer displays was implemented and display photographs were captured with
      different accommodation states of camera. With the simulation results and
      experimental results, this system was confirmed to support accommodation cues in
      a range of 1.8 diopters.

PMID- 30119533
TI  - Low cost, compact 4-DOF measurement system with active compensation of beam
      angular drift error.
AB  - In this paper, a compact four-degree-of-freedom (4-DOF) measurement system is
      presented. With a special optical configuration, the pitch error, yaw error, and
      two straightness errors of the moving target are able to be detected by only a
      single laser beam from a collimated laser diode. A 2D hybrid mirror angle
      steering mount is designed to perform the large angle turning for the axis
      alignment and very fine angle tuning by PZT actuators for real-time beam drift
      compensation. A series of calibration and comparison experiments have been
      carried out to verify the performance of the proposed system. The developed
      active compensation system could effectively suppress the beam's angular drift to
      within +/- 0.01 arc-sec in both of yaw and pitch directions. The developed 4-DOF
      measuring system is compact, low cost, and suitable for long distance geometric
      error measurement of linear stages.

PMID- 30119534
TI  - Quantitative phase imaging system with slightly-off-axis configuration and
      suitable for objects both larger and smaller than the size of the image sensor.
AB  - We propose a quantitative phase imaging system with exact slightly-off-axis
      configuration and suitable for objects both smaller and larger than the size of
      the effective recording region of the image sensors. In this system, the object
      is illuminated by a convergent spherical beam and a specially designed aperture
      filter is placed on the spatial frequency plane of the object wave; at the same
      time, a point source emitting from the edge of the aperture is taken as the
      reference beam, so that the optimal frequency condition for reconstruction of
      slightly-off-axis digital holograms can be always guaranteed for both large and
      small objects as well as different magnification (or the field of view)
      configurations. At the same time, a 1x2 single-mode optical fiber splitter is
      used for generating the reference and the illumination beams. Benefited from such
      fiber-based slightly-off-axis design, the proposed system provides a low-cost way
      to convert a regular microscope into a slightly-off-axis holographic one for
      microbiological specimens with a high spatial resolution.

PMID- 30119535
TI  - Theory of plasmon reflection by a 1D junction.
AB  - We present a comprehensive study of the reflection of normally incident plasmon
      waves from a low-conductivity 1D junction in a 2D conductive sheet. Rigorous
      analytical results are derived in the limits of wide and narrow junctions. Two
      types of phenomena determine the reflectance, the cavity resonances within the
      junction and the capacitive coupling between the leads. The resonances give rise
      to alternating strong and weak reflection but are vulnerable to plasmonic
      damping. The capacitive coupling, which is immune to damping, induces a near
      perfect plasmon reflection in junctions narrower than 1/10 of the plasmon
      wavelength. Our results are important for infrared 2D plasmonic circuits
      utilizing slot antennas, split gates or nanowire gates. They are also relevant
      for the implementation of nanoscale terahertz detectors, where optimal light
      absorption coincides with the maximal junction reflectance.

PMID- 30119536
TI  - Restriction on orbital angular momentum distribution: a role of media in vortex
      beams propagation.
AB  - The vortex beam carrying single orbital angular momentum (OAM) propagating
      through a medium with a certain transmission function is investigated. We show
      that the OAM mode weights in the output OAM spectrum involve two factors: the
      radial distribution of output beam power and the proposed restriction
      characterized function. Based on the restriction-characterized function, we show
      that the OAM mode weights can only vary in a limited range. We analyze the
      relationship between the radial distribution of the output beam power and the OAM
      mode weights in the output OAM spectrum. Finally, our theoretical analysis is
      illustrated numerically with the cases of eccentric circular aperture and
      atmospheric turbulence in a weak fluctuation regime. These results provide new
      insights into the characterization of the OAM spectrum and may find applications
      for fields involving OAM, such as an OAM-based optical communication link and
      object detection.

PMID- 30119537
TI  - Polarization-controlled multifrequency coherent perfect absorption in
      stereometamaterials.
AB  - We experimentally demonstrate polarization-controlled multifrequency coherent
      perfect absorption in stereometamaterials with twisted asymmetrically split
      rings. The coupling effects in stereometamaterials lead to the mode hybridization
      and thus multiple electric and magnetic resonances. The coherent perfect
      absorptions of electric and magnetic modes in stereometamaterials have been
      verified to be individually switched on/off by an interferometric effect of two
      counter-propagating coherent beams. The alternation of two orthogonal
      polarization states enables direct modulation of the operation frequencies of
      coherent perfect absorptions in both microwave and optical metamaterials. The
      work provides an opportunity to manipulate coherent perfect absorption and is
      helpful to design tunable multifrequency absorbers.

PMID- 30119538
TI  - Predictive capabilities for laser machining via a neural network.
AB  - The interaction between light and matter during laser machining is particularly
      challenging to model via analytical approaches. Here, we show the application of
      a statistical approach that constructs a model of the machining process directly
      from experimental images of the laser machined sample, and hence negating the
      need for understanding the underlying physical processes. Specifically, we use a
      neural network to transform a laser spatial intensity profile into an equivalent
      scanning electron microscope image of the laser-machined target. This approach
      enables the simulated visualization of the result of laser machining with any
      laser spatial intensity profile, and hence demonstrates predictive capabilities
      for laser machining. The trained neural network was found to have encoded
      functionality that was consistent with the laws of diffraction, hence showing the
      potential of this approach for discovering physical laws directly from
      experimental data.

PMID- 30119539
TI  - Theoretical modeling and analysis on the absorption cross section of the two
      photon excitation in Rb.
AB  - The cross-section is crucial for quantitative characterization and analysis of
      the absorption process. A model on the absorption cross-section of the
      simultaneous two-photon excitation in Rb-vapor four-wave mixing process is
      established by using the coupled-wave equation. Taken into account of the
      hyperfine structures for 85Rb and 87Rb, the third-order susceptibility and
      hyperfine line strength are calculated respectively. Then, the influences of
      hyperfine transition on cross section are investigated and simulation results
      agree well with the experiment results. The calculated results suggest that high
      pumping power intensity is essential in Rb two-photon excitation, while narrow
      linewidth is the limiting factor of high absorption efficiency by comparing
      normalized absorption profile between pumping beam and two-photon excitation
      process. Additionally, two approaches to improving absorption efficiency,
      linewidth narrowness of the pumping beam and absorption linewidth broadening, are
      proposed.

PMID- 30119540
TI  - Circular hole ENZ photonic crystal fibers exhibit high birefringence.
AB  - -A novel photonic crystal fiber (PCF) design that yields very high birefringence
      is proposed and analyzed. Its significantly enhanced birefringence is achieved by
      filling selected air holes in the cladding with an epsilon-near-zero (ENZ)
      material. Extensive simulation results of this asymmetric material distribution
      in the lower THz range demonstrate that the reported PCF has a birefringence
      above 0.1 and a loss below 0.01 cm-1 over a wide band of frequencies. Moreover,
      it exhibits near zero dispersion at 0.75 THz for both the X- and Y-polarization
      modes and a birefringence equal to 0.28. This THz PCF is then scaled successfully
      to optical frequencies. While the high birefringence is maintained, this optical
      PCF has a very high loss in its Y-polarization mode and, consequently, yields
      single-polarization single-mode (SPSM) propagation, exhibiting near zero
      dispersion at the optical telecom wavelength of 1.55 MUm. The ideal ENZ materials
      used for these conceptual models are replaced with realistic ones for both the
      THz and optical PCF designs. With the currently available ENZ materials, the
      realistic PCFs still have a high birefringence, but with higher losses compared
      to the idealized results. Future developments of ENZ materials that achieve lower
      loss properties will mitigate this issue in any frequency band of high interest.

PMID- 30119541
TI  - Matrix-masking to balance nonuniform illumination in microscopy.
AB  - With a perfectly uniform illumination, the amount and concentration of
      fluorophores in any (biological) sample can be read directly from fluorescence
      micrographs. However, non-uniform illumination in optical micrographs is a
      common, yet avoidable artefact, often caused by the setup of the microscope, or
      by inherent properties caused by the nature of the sample. In this paper, we
      demonstrate simple matrix-based methods using the common computing environments
      MATLAB and Python to correct nonuniform illumination, using either a background
      image or extracting illumination information directly from the sample image,
      together with subsequent image processing. We compare the processes, algorithms,
      and results obtained from both MATLAB (commercially available) and Python
      (freeware). Additionally, we validate our method by evaluating commonly used
      alternative approaches, demonstrating that the best nonuniform illumination
      correction can be achieved when a separate background image is available.

PMID- 30119542
TI  - Tunable optical chirality in a metamaterial platform with off-resonantly coupled
      metal-dielectric components.
AB  - Here we present a tunable chiral metamaterial platform that incorporates both
      metal and dielectric components, where the sign and magnitude of the circular
      dichroism (CD) response depend on the refractive index of the dielectric
      component. Using finite-difference time-domain simulations, we show that non
      resonant scattering interactions between the components of the system reverse the
      sign of the CD signal by changing the dissymmetry in absorption of circularly
      polarized light by the individual plasmonic components of the system. The
      platform exhibits tunable CD signal regardless of the shape and dimension of the
      dielectric scatterer, and the magnitude of the CD signal is enhanced by improving
      the scattering cross section of the dielectric structure. Finally, we show that
      the structure can be modified to incorporate other materials without diminishing
      the reversal in dissymmetry in transmission. These results indicate that
      controlled, off-resonant interactions between different materials in chiral
      metamaterials may be used to create tailored and tunable chiral platforms.

PMID- 30119544
TI  - GeSn lateral p-i-n photodetector on insulating substrate.
AB  - We report the first experimental demonstration of germanium-tin (GeSn) lateral p
      i-n photodetector on a novel GeSn-on-insulator (GeSnOI) substrate. The GeSnOI is
      formed by direct wafer bonding and layer transfer technique, which is promising
      for large-scale integration of nano-electronics and photonics devices. The
      fabricated GeSnOI photodetector shows well-behaved diode characteristics with
      high Ion/Ioff ratio of ~4 orders of magnitude (at +/- 1 V) at room temperature. A
      cutoff detection beyond 2 um with photo responsivity (Rop) of 0.016 A/W was
      achieved at the wavelength (lambda) of 2004 nm.

PMID- 30119543
TI  - LED-based visible light communication for color image and audio transmission
      utilizing orbital angular momentum superposition modes.
AB  - Twisted light has recently gained enormous interest in communication systems
      ranging from fiber-optic to radio frequency regimes. Thus far, the light-emitting
      diode (LED) has not yet been exploited for orbital angular momentum (OAM)
      encoding to transmit data, which, however, could open up an opportunity towards a
      new model of secure indoor communication. Here, by multiplexing and
      demultiplexing red, green and blue (RGB) twisted beams derived from a white light
      emitting diode, we build a new visible light communication system with RGB colors
      serving as independent channels and with OAM superposition modes encoding the
      information. At the sender, by means of theta-modulation, we use a computer
      controlled spatial light modulator to generate two-dimensional holographic
      gratings to encode a large alphabet with 16 different OAM superposition modes in
      each RGB channel. At the receiver, based on supervised machine learning, we
      develop a pattern recognition method to identify the characteristic mode patterns
      recorded by CCD cameras, and therefore, decoding the information. We succeed in
      demonstrating the transmission of color images and a piece of audio over a 6
      meter indoor link with the fidelity over 96%.

PMID- 30119545
TI  - Optical properties of plasmonic core-shell nanomatryoshkas: a quantum
      hydrodynamic analysis.
AB  - Plasmonic response of the metallic structure characterized by sub-nanometer
      dielectric gaps can be strongly affected by nonlocal or quantum effects. In this
      paper, we investigate these effects in spherical Na and Au nanomatryoshka
      structures with sub-nanometer core-shell separation. We use the state-of-the-art
      quantum hydrodynamic theory (QHT) to study both near-field and far-field optical
      properties of these systems: results are compared with the classical local
      response approximation (LRA), Thomas-Fermi hydrodynamic theory (TF-HT), and the
      reference time-dependent density functional theory (TD-DFT). We find that the
      results obtained using the QHT method are in a very good agreement with TD-DFT
      calculations, whereas other LRA and TF-HT significantly overestimate the field
      enhancements. Thus, the QHT approach efficiently and accurately describes
      microscopic details of multiscale plasmonic systems whose sizes are
      computationally out-of-reach for a TD-DFT approach; here, we report results for
      Na and Au nanomatryoshka with a diameter of 60 nm.

PMID- 30119546
TI  - Color gamut mapping between small and large color gamuts: part II. gamut
      extension.
AB  - A wide color gamut (WCG) display has great color rendering capability and offers
      the opportunity to achieve a pleasing and realistic appearance in terms of image
      quality. To take full advantage of the large display gamut, a new gamut extension
      algorithm (GEA) is proposed based on a new color appearance scale, vividness. The
      performance of the new GEA was investigated via a psychophysical experiment
      together with five commonly used GEAs. In addition, two different uniform color
      spaces (UCSs) were also studied including the CAM02-UCS color space and a space,
      Jzazbz, designed for high dynamic range (HDR) and WCG applications. The results
      showed that the newly proposed GEA, i.e. the vividness-extension (VE) algorithm,
      outperformed all the other GEAs and the Jzazbz space was a promising UCS for
      evaluating gamut extension.

PMID- 30119547
TI  - Sensitive and stable vector magnetometer for operation in zero and finite fields.
AB  - We report on an optically pumped magnetometer that uses multiple laser beams to
      pump and probe spin-polarized Cs atoms. The selected sensor geometry allows for
      operation in finite magnetic fields as well as close to zero field. In finite
      fields the magnetometer employs free spin precession signals to determine the
      field modulus and direction as described in a separate publication. This
      publication focuses on the magnetometer operation close to zero field, which is
      based on a ground state Hanle resonance. The four laser beams permit the
      simultaneous measurement of two orthogonal magnetic field components in a
      differential detection scheme that greatly suppresses technical laser power
      noise. Sensitivities better than 54 fT/Hz1/2 could be demonstrated simultaneously
      for both measurement channels in a well shielded environment. A minimum Allan
      deviation, limited by residual field fluctuations, of better than 40 fT was
      observed for integration times of 2s. The magnetometer achieves high sensitivity
      and stability in offset fields as well as close to zero field and is, thus, a
      universal tool for low frequency magnetic field measurements.

PMID- 30119548
TI  - Polarization-multiplexed nonlinear inverse synthesis with standard and reduced
      complexity NFT processing.
AB  - In this work, we study the performance of polarization division multiplexing
      nonlinear inverse synthesis transmission schemes for fiber-optic communications,
      expected to have reduced nonlinearity impact. Our technique exploits the
      integrability of the Manakov equation-the master model for dual-polarization
      signal propagation in a single mode fiber-and employs nonlinear Fourier transform
      (NFT) based signal processing. First, we generalize some algorithms for the NFT
      computation to the two- and multicomponent case. Then, we demonstrate that
      modulating information on both polarizations doubles the channel information rate
      with a negligible performance degradation. Moreover, we introduce a novel dual
      polarization transmission scheme with reduced complexity which separately
      processes each polarization component and can also provide a performance
      improvement in some practical scenarios.

PMID- 30119549
TI  - Orbital angular momentum sidebands of vortex beams transmitted through a thin
      metamaterial slab.
AB  - A pure vortex beam carrying m-order orbital angular momentum (OAM) will be
      deformed when transmitting through a thin slab, and "neighboring" sideband {m +
      1} and {m-1} modes will emerge. The emergence of the OAM sideband is accompanied
      with OAM-dependent Goos-Hanchen (GH) shift. When the energies carried by the {m}
      mode of the transmitted beam and by the sideband modes are identical, the OAM
      dependent shifts reach their upper limits, |m|w0/2(|m| + 1)1/2, where w0 is the
      incident beam waist. The epsilon-near-zero metamaterial is found to be suitable
      to achieve the upper-limited OAM-dependent GH shifts. These findings provide a
      deeper insight into the beam shifts of vortex beams and have potential
      applications in the optical sensing, detection of OAM, and other OAM-based
      applications.

PMID- 30119550
TI  - Femtosecond-induced spiral micro-structured SMS fiber structure for refractive
      index measurement.
AB  - A single-multi-single mode (SMS) fiber structure with spiral microgroove,
      fabricated by femtosecond laser inscription has been proposed and successfully
      employed for refractive index (RI) sensing. The multimode interference in the SMS
      structure is effectively affected by the external perturbation due to the
      microgroove, which goes deep into the core of the multimode fiber (MMF).
      Experimental results show that this femtosecond-induced spiral micro-structured
      SMS (FISM-SMS) fiber structure exhibits a linear response to eternal liquid
      refractive index in a large RI range of 1.3373-1.4345. The maximum sensitivity of
      the structure can reach to 2144 nm/RIU and can be further improved by increasing
      the depth of the spiral micro-grooves.

PMID- 30119551
TI  - Electrically controllable THz asymmetric split-loop resonator with an outer
      square loop based on VO2.
AB  - In this paper, we propose an asymmetric split-loop resonator with an outer square
      loop (ASLR-OSL) based on vanadium dioxide (VO2) which can actively control the
      transmission characteristics of a terahertz wave while maintaining a high quality
      factor of the asymmetric split-loop resonator (ASLR) by adding an outer square
      loop. The proposed ASLR-OSL demonstrated transmission characteristics similar to
      those of ASLR, and the transmission characteristics of ASLR-OSL were successfully
      controlled by directly applying a bias voltage. These results show a simple
      method for imposing active properties on a common metamaterial having a high
      quality factor by adding a loop structure.

PMID- 30119552
TI  - Position-deviation-compensation demodulation method for multi-channel polarized
      low-coherence interferometry.
AB  - A position-deviation-compensation demodulation method is proposed to improve the
      channel adaptability of Fabry-Perot (F-P) sensor in a multi-channel optical fiber
      F-P sensing system. By combining the envelope peak position (EPP) retrieval
      process and the position compensation process, the proposed method enables the
      accurate demodulation of F-P sensors in all channels. Thereinto, the EPP
      retrieval process uses the phase information to recover the EPP with high
      precision; the position compensation process compensates the position deviation
      by an optical-path-based model, which is established to illustrate the principle
      of the position deviation between different channels. We carried out the pressure
      experiment to verify the effectiveness of the proposed method. The experiment
      results showed that the demodulation errors of all channels are no more than 0.13
      kPa, which demonstrated that our approach is reliable for improving the channel
      adaptability of F-P sensors.

PMID- 30119553
TI  - Single-channel 7.68 Tbit/s, 64 QAM coherent Nyquist pulse transmission over 150
      km with a spectral efficiency of 9.7 bit/s/Hz.
AB  - We achieved a record capacity of 7.68 Tbit/s in a single-channel OTDM
      transmission with a 9.7 bit/s/Hz spectral efficiency, where a polarization
      multiplexed 640 Gbaud, 64 QAM coherent Nyquist pulse has been transmitted over
      150 km. In this scheme, a 1.39 ps optical Nyquist pulse with an OSNR of 53 dB at
      a 0.1 nm resolution was generated by combining a mode-locked laser and a highly
      nonlinear fiber and used at both the transmitter and receiver. Phase
      synchronization was achieved between these pulse sources with an advanced optical
      phase-locked loop based on the higher harmonics of the mode-locked laser mode. In
      addition, we suppressed a nonlinear phase rotation at an EDFA in the transmitter
      by broadening the pulse width with second-order dispersion and recompressed it to
      the original pulse width before a 150 km transmission link. We succeeded in a bit
      error rate below 2 x 10-2 for all tributaries.

PMID- 30119554
TI  - All-fiber stable orbital angular momentum beam generation and propagation.
AB  - An all-fiber scheme for stable orbital angular momentum (OAM) beam generation and
      propagation is proposed and demonstrated. This scheme is based on a self-designed
      and manufactured graded-index few mode fiber (GI-FMF) and compatible mode
      selection coupler (MSC). The MSC, which consists of a conventional single mode
      fiber (SMF) and the GI-FMF, can effectively couple the fundamental mode in the
      SMF to the desired OAM mode in the GI-FMF based on phase matching condition.
      Meanwhile, the GI-FMF breaks the degeneracy between the desired eigenmodes and
      neighboring vector modes, thereby allowing the preservation and propagation of
      the selectively excited OAM modes. As a proof-of-principle, we have implemented
      an all-fiber device operating in stable OAM modes with |l| = 1. The experimental
      results show stable propagation of OAM beams with the mode purity of ~95% and
      bandwidth of 100 nm. This all fiber device could be useful for further
      development of wide bandwidth OAM mode division multiplexed application.

PMID- 30119555
TI  - Simultaneous distributed static and dynamic sensing based on ultra-short fiber
      Bragg gratings.
AB  - Distributed static and dynamic sensing is demonstrated with an ultra-short fiber
      Bragg grating (USFBG) array. The USFBGs serve as the sensors and reflection
      mirrors at the same time. Distributed static sensing is performed by demodulating
      the strain-induced or temperature-induced wavelength shift of each USFBG. Dynamic
      vibration sensing is realized based on phase variation between two adjacent USFBG
      reflected pulses. Static temperature and dynamic vibration are applied to the
      sensing ultra-short FBG array simultaneously. The experiments show that the
      temperature measurement from 30  degrees C to 80  degrees C is achieved
      successfully. And dynamic sensing of nepsilon scale vibration and 12.5 kHz
      acoustic wave are demonstrated at a sampling rate of 50 kHz.

PMID- 30119556
TI  - Trifunctional metasurfaces: concept and characterizations.
AB  - Achieving multiple diversified functionalities in a single flat device is crucial
      for electromagnetic (EM) integration. While many recent efforts were devoted to
      designing multifunctional metasurfaces, most meta-devices realized so far
      typically exhibit only two functionalities. In this paper, we propose a generic
      strategy to design trifunctional metasurfaces, based on carefully designed single
      structure meta-atoms possessing polarization-controlled transmission/reflection
      properties. As a proof of our concept, we design and fabricate a trifunctional
      metasurface possessing simultaneously three distinct functionalities including
      beam splitting, deflecting, and focusing, and perform both far-field and near
      field microwave experiments to demonstrate the predicted functionalities of the
      fabricated device. Experimental results are in good agreement with numerical
      simulations. These findings can motivate the realizations of high-performance
      multifunctional meta-devices in different frequency domains and with diversified
      functionalities.

PMID- 30119558
TI  - Full bandwidth dynamic coarse integral holographic displays with large field of
      view using a large resonant scanner and a galvanometer scanner.
AB  - An efficient method to implement the coarse integral holographic (CIH) concept
      for dynamic CIH displays is to scan the information generated from a spatial
      light modulator (SLM) of a low space bandwidth product (SBP) but high bandwidth
      to form the hologram array for the integral optics. Previously, just over half of
      the SLMs bandwidth was utilized due to the fact that the galvanometer scanner in
      use could not tile all the holograms that the SLM is capable to produce,
      resulting in the loss of nearly half of the field of view (FOV). Here, we propose
      a full bandwidth dynamic CIH display using a large resonant scanner in
      conjunction with a hybrid raster scanner, which can utilize the full bandwidth of
      the spatial light modulator and double the horizontal FOV. Experimental results
      confirm that with the SLM and scanners as used, the FOV can reach 48 degrees 
      when the SLM reaches its full bandwidth. This approach can be used for future
      scalable and tileable CIH display systems.

PMID- 30119557
TI  - Composite filtering effect in a SESAM mode-locked fiber laser with a 3.2-GHz
      fundamental repetition rate: switchable states from single soliton to pulse
      bunch: erratum.
AB  - We present the erratum regarding the x-axis label in two figures, a numerical
      correction and a mathematical symbol correction.

PMID- 30119559
TI  - Nearly diffraction-limited hard X-ray line focusing with hybrid adaptive X-ray
      mirror based on mechanical and piezo-driven deformation.
AB  - We have developed the new hybrid adaptive X-ray mirror based on mechanical and
      piezo-driven deformation to realize precise shape controllability on a long
      length mirror. The mechanical bender approximately provides the required ellipse,
      while the piezoelectric actuators attached to the mirror correct very small
      residual errors to satisfy the diffraction-limited condition. The mechanical
      bender significantly reduces the role of the piezoelectric actuator, resulting in
      the suppression of accuracy degradation due to the drift and/or junction effect
      of the piezoelectric actuators. In addition, line focusing was demonstrated with
      two different numerical apertures at SPring-8, and the obtained beam sizes were
      127 and 253 nm (FWHM), which agree well with the diffraction-limited sizes.

PMID- 30119560
TI  - Fast two-step layer-based method for computer generated hologram using sub-sparse
      2D fast Fourier transform.
AB  - Fast two-step layer-based and sub-sparse two-dimensional Fast Fourier transform
      (SS-2DFFT) algorithms are proposed to speed up the calculation of computer
      generated holograms. In a layer-based method, each layer image may contain large
      areas in which the pixel values are zero considering the occlusion effect among
      the different depth layers. By taking advantage of this feature, the two-step
      layer-based algorithm only calculates the non-zero image areas of each layer. In
      addition, the SS-2DFFT method implements two one-dimensional fast Fourier
      transforms (1DFFT) to compute a 2DFFT without calculating the rows or columns in
      which the image pixels are all zero. Since the size of the active calculation is
      reduced, the computational speed is considerably improved. Numerical simulations
      and optical experiments are performed to confirm these methods. The results show
      that the total computational time can be reduced by 5 times for a three
      dimensional (3D) object of a train, 3.4 times for a 3D object of a castle and 10
      times for a 3D object of a statue head when compared with a conventional layer
      based method if combining the two proposed methods together.

PMID- 30119561
TI  - Comparative study of quantitative phase imaging techniques for refractometry of
      optical waveguides.
AB  - A comparative study of quantitative phase imaging techniques for refractometry of
      optical waveguides is presented. Three techniques were examined: a method based
      on the transport-of-intensity equation, quadri-wave lateral shearing
      interferometry and digital holographic microscopy. The refractive index profile
      of a SMF-28 optical fiber was thoroughly characterized and served as a gold
      standard to assess the accuracy and precision of the phase imaging methods.
      Optical waveguides were inscribed in an Eagle2000 glass chip using a femtosecond
      laser and used to evaluate the sensitivity limit of these phase imaging
      approaches. It is shown that all three techniques provide accurate, repeatable
      and sensitive refractive index measurements. Using these phase imaging methods,
      we report a comprehensive map of the photosensitivity to femtosecond pulses of
      Eagle2000 glass. Finally, the reported data suggests that the phase imaging
      techniques are suited to be used as precise and non-destructive refractive index
      shift measuring tools to study and control the inscription process of optical
      waveguides.

PMID- 30119562
TI  - Enhanced random laser by metal surface-plasmon channel waveguide.
AB  - Compared with conventional lasers, the random laser is realized through strong
      multiple scatterings in disordered gain system. In this paper, random lasing (RL)
      in one-dimensional metal surface plasmon (SP) waveguide with gold-plated self
      formed silicon pyramids was investigated comprehensively. Consequently, the
      emission intensity of RL was enhanced dramatically and the RL threshold was
      reduced significantly through Au-coated Si spiky tips. Meanwhile, one-dimensional
      metal SP channel waveguides confined the emitting light in a certain direction
      with a small divergence angle. Using FDTD simulations, it was found that the
      enhancement effect for RL is likely attributed to the localized surface plasmon
      (LSP) field. In addition, the LSP field nearby the spiky tips can enhance field
      molecule interaction, which was benefit for lasing in small scale. The results in
      this letter supplied a feasible method to realize the application of RL in
      subwavelength optical elements.

PMID- 30119563
TI  - Low-repetition-rate all-fiber integrated optical parametric oscillator for
      coherent anti-Stokes Raman spectroscopy.
AB  - All-fiber optical parametric oscillator (OPO), offering advantages like
      robustness, compactness and low lost, has attracted intense interest in coherent
      anti-Stokes Raman scattering spectroscopy. In typical fiber-based OPO
      configurations, detrimental nonlinear effects due to intense pump field in fiber
      coupling devices would inevitably degrade the spectral purity and conversion
      efficiency, especially when the OPO operated at low repetition rates. Here we
      demonstrated a new OPO design by placing the main amplifier inside the cavity,
      where the amplified pump pulses were directly coupled into the nonlinear fiber.
      Consequently, lower threshold, higher output power and narrower spectrum were
      obtained. In particular, effective suppression of spectral noise was
      experimentally observed, resulting in threshold reductions of 37.5%, 17.2%, and
      5.2% with a comparison to a conventional OPO operating at repetition rates of 1,
      2 and 3 MHz, respectively. Furthermore, the generated synchronized two-color
      laser sources at a low repetition rate were then employed to detect CH
      vibrational bands in an ethanol sample. This spectral tailored cavity design is
      expected to greatly promote the spread of compact all-fiber laser source to
      nonlinear biomedical imaging.

PMID- 30119564
TI  - Photonics-based MIMO radar with high-resolution and fast detection capability.
AB  - A photonics-based multiple-input-multiple-output (MIMO) radar is proposed and
      demonstrated based on wavelength-division-multiplexed broadband microwave
      photonic signal generation and processing. The proposed radar has a large
      operation bandwidth, which helps to achieve an ultra-high range resolution.
      Compared with a monostatic radar, improved radar performance and extended radar
      applications originated from the MIMO architecture can be achieved. In addition,
      low-speed electronics with real-time signal processing capability is feasible. A
      photonics-based 2 * 2 MIMO radar is established with a 4-GHz bandwidth in each
      transmitter and a sampling rate of 100 MSa/s in the receiver. Performance of the
      photonics-based multi-channel signal generation and processing is evaluated, and
      an experiment for direction of arrival (DOA) estimation and target positioning is
      demonstrated, through which the feasibility of the proposed radar system can be
      verified.

PMID- 30119565
TI  - Low-frequency nonlocal and hyperbolic modes in corrugated wire metamaterials.
AB  - Metamaterials based on arrays of aligned plasmonic nanowires have recently
      attracted significant attention due to their unique optical properties that
      combine tunable strong anisotropy and nonlocality. These optical responses
      provide a platform for implementation of novel sensing, imaging, and quantum
      optics applications. Basic building blocks, used for construction of those
      peculiar composites, are plasmonic metals, such as gold and silver, which have
      moderate negative values of permittivities at the optical spectral range. Scaling
      the plasmonic behavior to lower frequencies remains a longstanding challenge also
      owing to the emergence of strong spatial dispersion in homogenized artificial
      composites. At lower THz and GHz frequencies, the electromagnetic response of
      noble metals approaches that of perfect electric conductors, preventing
      straightforward scaling of visible-frequency plasmonics to the frequency domains
      that are important for a vast range of applications, including wireless
      communications, microwave technologies and many others. Here we demonstrate that
      both extreme anisotropy (so-called hyperbolicity) and nonlocality of artificial
      composites can be achieved and designed in arrays of corrugated perfectly
      conducting wires at relatively low GHz frequencies. The key concept is based on
      hybridization of spoof plasmon polariton modes that in turn emulate surface
      polariton waves in systems with corrugated interfaces. The method makes it
      possible to map the recent developments in the field of plasmonics and
      metamaterials to the domain of THz and RF photonics.

PMID- 30119566
TI  - Gradient cross-correlation algorithm for scene-based Shack-Hartmann wavefront
      sensing.
AB  - Scene-based wavefront sensing currently uses the periodic-correlation algorithm
      based on fast Fourier transforms. However, when the object scene contains
      features at the field edges, the performance of the algorithm is poor due to the
      periodicity of fast Fourier transforms, called wraparound effect. In this paper,
      we propose an algorithm based on the gradient cross-correlation. Both simulation
      and experiment results show its dramatic effectiveness against the wraparound
      effect, and a considerable improvement is obtained in image resolution with
      closed loop adaptive optics correction.

PMID- 30119567
TI  - Control the orbital angular momentum in third-harmonic generation using quasi
      phase-matching.
AB  - Manipulating photon's orbital angular momentum (OAM) through nonlinear
      interactions has drawn increasing research interests in recent years. In this
      work, we propose a scheme to control the OAM of the third harmonic wave through
      two cascaded second-order nonlinear processes. A Gaussian beam was frequency
      doubled at the first stage. Subsequent sum frequency mixing of the Gaussian
      second harmonic wave and an orthogonal-polarized Laguerre-Gaussian-like
      fundamental wave generate the third harmonic wave, which carries the same OAM as
      that of the Laguerre-Gaussian-like fundamental wave. In this experiment, we
      demonstrated controlling the OAM of the third harmonic wave in a tandem
      periodically-poled LiTaO3 optical superlattice, and the results are in accordance
      with theoretical predictions.

PMID- 30119568
TI  - Analytical insights into self-phase modulation: beyond the basic theory.
AB  - We present a closed-form analytical description of the early stages of spectral
      broadening of ultrashort laser pulses beyond the basic theory of self-phase
      modulation (SPM). In the limit of short propagation paths, approximate analytical
      expressions derived as a part of our treatment recover the canonical SPM-theory
      results for the nonlinear shift and spectral broadening. For longer propagation
      paths, these expressions shed light on how dispersion effects enter the scene,
      decelerating the spectral broadening in the regime of normal dispersion and
      giving rise to an explosion-like bandwidth growth in anomalous-dispersion high
      soliton-number pulse evolution scenarios. Based on this formalism, we will
      provide an analytical derivation for the relation between the maximum soliton
      self-compression length and the soliton number, which has been previously treated
      as purely empirical.

PMID- 30119569
TI  - High-performance integral-imaging-based light field augmented reality display
      using freeform optics.
AB  - A new integral-imaging-based light field augmented-reality display is proposed
      and implemented for the first time, to our best knowledge, to achieve a wide see
      through view and high image quality over a large depth range. By using custom
      designed freeform optics and incorporating a tunable lens and an aperture array,
      we demonstrated a compact design of a light field head-mounted-display that
      offers a true 3D display view of 30 degrees  by 18 degrees , maintains a spatial
      resolution of 3 arc minutes across a depth range of over 3 diopters, and provides
      a see-through field of view of 65 degrees  by 40 degrees .

PMID- 30119570
TI  - Q-switching and quasi-phase-matching using a domain structured LiNbO3 crystal.
AB  - We report a device that acts as an active Q-switch and a quasi-phase-matching
      structure. It is a domain-structured LiNbO3 crystal, where the Q-switching is
      performed by electro-optic deflection and the wavelength conversion is produced
      by quasi-phase-matched optical parametric generation. By introducing this device
      into a diode-pumped Nd:YAG laser we obtained pulses at 1064 nm (~10 ns FWHM, 195
      uJ) and 1617 nm (~3 ns, 15 uJ).

PMID- 30119572
TI  - Optical properties of oxygen vacancies in HfO2 thin films studied by absorption
      and luminescence spectroscopy.
AB  - Hafnium oxide thin films with varying oxygen content were investigated with the
      goal of finding the optical signature of oxygen vacancies in the film structure.
      It was found that a reduction of oxygen content in the film leads to changes in
      both, structural and optical characteristics. Optical absorption spectroscopy,
      using nanoKelvin calorimetry, revealed an enhanced absorption in the near
      ultraviolet (near-UV) and visible wavelength ranges for films with reduced oxygen
      content, which was attributed to mid-gap electronic states of oxygen vacancies.
      Absorption in the near-infrared was found to originate from structural defects
      other than oxygen vacancy. Luminescence generated by continuous-wave 355-nm laser
      excitation in e-beam films showed significant changes in the spectral profile
      with oxygen reduction and new band formation linked to oxygen vacancies. The
      luminescence from oxygen-vacancy states was found to have microsecond-scale
      lifetimes when compared with nanosecond-scale lifetimes of luminescence
      attributed to other structural film defects. Laser-damage testing using
      ultraviolet nanosecond and infrared femtosecond pulses showed a reduction of the
      damage threshold with increasing number of oxygen vacancies in hafnium oxide
      films.

PMID- 30119571
TI  - Time-gated chaotic Brillouin optical correlation domain analysis.
AB  - A new technology for chaotic Brillouin optical correlation domain analysis
      (BOCDA) has been proposed and experimentally demonstrated with high spatial
      resolution. However, the off-peak amplification induced by the chaotic
      autocorrelation sidelobes limits the measurement range of chaotic BOCDA system.
      The time-gated scheme is introduced to suppress the off-peak amplification. With
      the pump pulse of 120 ns duration, the time-gated chaotic BOCDA has been
      experimentally achieved with a 9 cm spatial resolution over a 10.2 km measurement
      range. The standard deviation in the local Brillouin frequency shift is +/- 1.8
      MHz.

PMID- 30119573
TI  - One-shot carrier fringe polarimeter in a double-aperture common-path
      interferometer.
AB  - This paper presents a novel, simple, robust, and very stable polarimeter which is
      able to measure in a single-shot the state of polarization (SOP) of an optical
      field. In this proposal, an optical field with an unknown SOP and an optical
      field with a reference SOP are superposed by using a double aperture common-path
      interferometer (DACPI), obtaining two interferograms with adjustable carrier
      frequency in a single shot. Each interferogram has different visibility and phase
      step where the information of the unknown SOP is contained. It is shown that
      under a typical Fourier analysis any SOP can be successfully measured without the
      necessity of knowing the carrier frequency. The present proposal is justified
      mathematically and probed experimentally.

PMID- 30119574
TI  - Dynamically reconfigurable sources for arbitrary Gaussian states in integrated
      photonics circuits.
AB  - We present a modular design for integrated programmable multimode sources of
      arbitrary Gaussian states of light. The technique is based on current
      technologies, in particular recent demonstrations of on-chip photon manipulation
      and the generation of highly squeezed vacuum states in semiconductors. While the
      design is generic and independent of the choice of integrated platform, we adopt
      recent experimental results on compound semiconductors as a demonstrative
      example. Such a device would be valuable as a source for many quantum protocols
      that range from imaging to communication and information processing.

PMID- 30119575
TI  - Avalanche parametric conversion and white spectrum generation from infrared
      femtosecond pulses in glasses.
AB  - The observation of discrete lines in the white spectrum at the initial stage of
      filamentation of powerful femtosecond laser pulses, propagating in silica
      glasses, as well as the filamentation without plasma channels observed in the
      experiments in air, pushed us to look for other nonlinear mechanisms for
      describing these effects. In this paper, we present a new parametric conversion
      mechanism for asymmetric spectrum broadening of femtosecond laser pulses towards
      higher frequencies in isotropic media. This mechanism includes cascade generation
      with THz spectral shift for solids and GHz shift for gases. The process works
      simultaneously with the four-photon parametric wave mixing. The theoretical model
      proposed agrees well with the experimental data.

PMID- 30119577
TI  - Role of loss in all-dielectric metasurfaces.
AB  - Arrays of dielectric cylinders support two fundamental dipole active eigenmodes,
      which can be manipulated to elicit a variety of electromagnetic responses in all
      dielectric metamaterials. Dissipation is a critical parameter in determining
      functionality; the present work varies material loss to explore the rich
      electromagnetic response of this class of metasurface. Four experimental cases
      are investigated which span electromagnetic response ranging from Huygens
      surfaces with transmissivity T = 94%, and phase phiS21 = 235 degrees , to
      metasurfaces which absorb 99.96% of incident energy. We find perfect absorption
      to be analogous to the driven damped harmonic oscillator, with critical damping
      occurring at resonance. With high phase contrast, transmission, and absorption
      all accessible from a single system, we present a uniquely diverse all-dielectric
      system.

PMID- 30119576
TI  - Zadoff-Chu sequence-based upstream ranging in OFDMA-PON mobile radio access
      networks.
AB  - Orthogonal frequency division multiple access (OFDMA) uplink in a passive optical
      network (PON) requires the delay alignment for OFDMA symbols from remotely
      distributed optical network units (ONUs). In this paper, we experimentally
      demonstrate and analyze the performance of a Zadoff-Chu (ZC) sequence-based
      upstream ranging scheme in an intensity modulation/direct detection (IM/DD)-based
      OFDMA-PON. The experimental results show that the proposed scheme can achieve
      upstream synchronization with only marginal inter-carrier interference (ICI) and
      requires no additional bandwidths in a typical OFDMA transmission with cyclic
      prefix (CP).

PMID- 30119578
TI  - Low-loss and low-crosstalk multimode waveguide bend on silicon.
AB  - A low-loss and low-crosstalk multimode waveguide bend is proposed and
      demonstrated for mode-division-multiplexed optical interconnects. The proposed 90
      degrees -bend is composed of two identical 45 degrees -bends, which are defined
      as modified Euler curves. For the designed 90 degrees  Euler-bend with a core
      width of 2.36 MUm for supporting four TM-polarization modes, it is allowed to
      achieve an effective radius as small as 45 MUm, which is about 1/4 of the radius
      (~175 MUm) for a regular 90 degrees  arc-bend. In theory, this proposed 90
      degrees  Euler-bend has very low excess losses (<0.1 dB) and very low inter-mode
      crosstalks (<-25 dB) over a broad wavelength-band. A silicon photonic integrated
      circuit is designed, fabricated and characterized by integrating a pair of mode
      (de)multiplexers and a multimode bus waveguide with a Euler S-bend consisting of
      two cascaded 90 degrees  Euler-bends. The measurement results show that the
      fabricated Euler S-bend has low excess losses of <0.5 dB and low inter-mode
      crosstalks of <-20 dB over a broad band from 1520 nm to 1610 nm for all the 4
      mode-channels of TM polarization.

PMID- 30119579
TI  - Use of distributed acoustic sensing for Doppler tracking of moving sources.
AB  - Distributed acoustic sensing (DAS) via fiber-optic reflectometry techniques is
      finding more and more applications in recent years. In many of these
      applications, the position of detected acoustic or seismic sources is defined
      with a single longitudinal coordinate which specifies the distance between the
      detection point in the fiber to the DAS interrogator. In this paper we describe a
      DAS system which is intended to operate in a fluid (air or water) and to detect
      and localize moving objects, with three spatial coordinates, using the acoustic
      waves they generate or reflect and their Doppler shifts. The new method uses
      optical frequency domain reflectometry (OFDR) and lumped Rayleigh reflectors
      (LRR's) to ensure sufficiently high sensitivity for operation in fluid media. The
      new method was used to track a narrowband (CW) signal source.

PMID- 30119580
TI  - Polarization-insensitive fiber-coupled superconducting-nanowire single photon
      detector using a high-index dielectric capping layer.
AB  - Superconducting-nanowire single photon detectors (SNSPDs) are able to reach near
      unity detection efficiency in the infrared spectral range. However, due to the
      intrinsic asymmetry of nanowires, SNSPDs are usually very sensitive to the
      polarization of the incident radiation, their responsivity being maximum for
      light polarized parallel to the nanowire length (transverse-electric (TE)
      polarization). Here, we report on the reduction of the polarization sensitivity
      obtained by capping NbN-based SNSPDs with a high-index SiNx dielectric layer,
      which reduces the permittivity mismatch between the NbN wire and the surrounding
      area. Experimentally, a polarization sensitivity below 0.1 is obtained both at
      1.31 and 1.55 um, in excellent agreement with simulations.

PMID- 30119581
TI  - Hyperspectral ghost imaging camera based on a flat-field grating.
AB  - A spectral camera based on ghost imaging via sparsity constraints (GISC) acquires
      a three-dimensional (3D) spatial-spectral data cube of the target through a two
      dimensional (2D) detector in a single snapshot. However, the spectral and spatial
      resolution are interrelated because both of them are modulated by the same
      spatial random phase modulator. In this paper, we theoretically and
      experimentally demonstrate a system by equipping the GISC spectral camera with a
      flat-field grating to disperse the light fields before the spatial random phase
      modulator, hence consequently decoupling the spatial and spectral resolution. By
      theoretical derivation of the imaging process we obtain the spectral resolution
      1nm and spatial resolution 50MUm about the new system which are verified by the
      experiment. The new system can not only modulate the spatial and spectral
      resolution separately, but also provide a possibility of optimizing the light
      field fluctuations of different wavelengths according to the imaging scene.

PMID- 30119582
TI  - Field imaging system for hyperspectral data, 3D structural data and panchromatic
      image data measurement based on acousto-optic tunable filter.
AB  - The hyperspectral data and 3D structural data are highly useful in botanical
      research. But, the two types of information are often acquired separately and
      hard to be combined. In this work, a novel dual-path configuration based on
      acousto-optical tunable filter (AOTF) is proposed to acquire an image, structural
      and hyperspectral information within one acquisition process by a combination of
      laser triangulation. Under the configuration, the hyperspectral data and the 3D
      structure can be matched to subpixel level after geometrical calibration.
      Finally, the obtainment of 3D hyperspectral information in field experiment
      verifies the feasibility of this imaging system.

PMID- 30119583
TI  - Diode-wing-pumped electro-optically Q-switched 2 MUm laser with pulse energy
      scaling over ten millijoules.
AB  - Characteristics of diode-wing-pumped highly efficient Tm:LuAG lasers running both
      in continuous wave (CW) and electro-optical Q-switching regimes have been
      investigated. Using a simple plane-plane cavity, a maximum CW output power of 8.5
      W has been achieved with a corresponding slope efficiency of 44.5% by "wing
      pumping" at 790 nm. With a V-shaped cavity, a diode-wing-pumped MgO:LiNbO3
      crystal based electro-optically Q-switched Tm:LuAG laser at 2022.9 nm delivered a
      maximum pulse energy of 10.8 mJ and a minimum pulse width of 52 ns at a
      corresponding repetition rate of 100 Hz. To the best of our knowledge, the
      achieved CW output power and Q-switched pulse energy have both set records for
      all-solid-state Tm:LuAG lasers, which well reveals an efficient way to generate
      high-power and high-energy lasers at 2 MUm wavelength.

PMID- 30119584
TI  - Johnston's organ in Neodiprion sertifer (Insecta: Hymenoptera).
AB  - The fine structure of Johnston's organ in the pine sawfly, Neodiprion sertifer,
      was studied by electron microscopy to determine if there exists a dimorphism in
      this organ corresponding to the sexual dimorphism in antennal shape and surface
      area. The organ is made up of scolopidia that are ultrastructurally similar to
      those of other insects. The scolopidia, identical in both sexes, comprise three
      sensory cells bearing two types of sensory processes: Two are shorter and smaller
      in diameter than the third, which extends into the cuticle of the membrane
      connecting pedicel and flagellum and terminates at an epicuticular invagination.
      The dendrites and sensory processes are surrounded by two types of enveloping
      (glial) cells-a scolopale cell and an attachment cell. Other enveloping cells
      occur at different levels of the scolopidium. Sexual dimorphism is evident only
      in the numbers of scolopidial groups: Males have more groups with fewer
      scolopidia, but both sexes possess about the same total number of scolopidia.

PMID- 30119585
TI  - Heterochronic mechanisms of morphological diversification and evolutionary change
      in the neotropical salamander, Bolitoglossa occidentalis (Amphibia:
      Plethodontidae).
AB  - Bolitoglossa occidentalis, a lowland salamander of Mexico and Guatemala, has a
      highly derived morphology. The features that are derived with respect to the
      condition in generalized members of the genus include the following: (1) small
      body size; (2) short tail; (3) fully webbed hands and feet; (4) reduction and
      loss of certain phalangeal elements; (5) fusion of carpals and tarsals; (6)
      absence of prefrontal bones; and (7) reduced skull ossification. The ontogeny of
      this species was analyzed quantitatively and compared with the patterns of growth
      and differentiation encountered in two morphologically generalized members of the
      genus, B. rostrata and B. subpalmata. Most of the derived features can be
      explained by invoking a single heterochronic process: truncation of development
      at a small size (most likely the product of early maturation). Therefore, B.
      occidentalis is a paedomorphic species whose morphology has been attained through
      the process of progenesis. This result supports Alberch's ('80a) prediction,
      based on functional analysis, that the principle adaptation to arboreality in B.
      occidentalis is small size; other derived morphological features are associated
      with the organism's truncated development and may have no adaptive significance.
      However, patterns of dissociation are found within this overall progenetic
      process. Some of these include the following: (1) accelerated growth rates of the
      metatarsals and first phalanges, and retarded growth rates of the second and
      third phalangeal elements; (2) dissociation between rates of ossification of the
      skull and the autopodial elements; and (3) dissociation between the timing of
      termination of the process of shape change during the ontogeny of the foot (the
      product of differential growth between digital and interdigital areas) and
      termination of growth in overall foot size (foot surface area). This later result
      illustrates the independence of morphogenetic phenomena (shape change) from
      processes of growth (size increase).

PMID- 30119586
TI  - Fine structure of the body wall, nervous system, and digestive tract in the
      Lobatocerebridae Rieger and the organization of the gliointerstitial system in
      Annelida.
AB  - The new family Lobatocerebridae, Rieger, contains a group of turbellariomorph
      worms in the annelid line of evolution. The fine structural organization of the
      body wall, the digestive tract, and parts of the central and peripheral nervous
      system are described and the findings are discussed in light of general
      invertebrate cytology. The epidermis and gastrodermis contain a basal granule
      cell system which is structurally very similar to the neuroglia cell system of
      the nervous system. The continuity of the neuroglia cell system, and the
      epidermal basal granule cell system and the basal granule cell system in the
      digestive epithelia suggests the existence of a single glial-basal granule cell
      system, similar to the gliointerstitial cell system first recognized in the
      Mollusca (see Nicaise, '73). The Annelida may show a dual (ectodermal and
      mesodermal) origin of such a gliointerstitial cell system as suggested by
      similarities in the epidermal basal cell system in the Oligochaeta and of certain
      epidermal and gastrodermal cells in polychaete regeneration with neuroglia in the
      Annelida. The structural similarity of neuroglia and basal granule cells in
      Lobatocerebridae may be the result of similarity in the formation, maintenance,
      or regulation of the extracellular matrix.

PMID- 30119587
TI  - External features of embryonic development of a jumping bristletail, Pedetontus
      unimaculatus Machida (Insecta, Thysanura, Machilidae).
AB  - The external features of the embryo and the first instar larva of Pedetontus
      unimaculatus are described. Blastokinesis of P. unimaculatus is very similar to
      that of Petrobius brevistylis (Larink, '69), but differs from that of Machilis
      alternata (Heymons and Heymons, '05). The superficial structures of three pairs
      of protocerebral lobes are present. The terga of the mandibular, maxillary, and
      labial segments take part in the formation of the head capsule. In the maxilla
      and labium, the palpi are homologous with the telopodites of the legs; the other
      parts proximal to the palpi are homologous with the coxopodites. No sternal
      element contributes to the postmentum. Both glossa and paraglossa consist of two
      lobes. The pleuropodium, stylus and ventral sac are derived from distal parts of
      appendage anlagen. The pleuropodium of the first abdominal segment is homologous
      with the styli of the successive abdominal segments; the ventral sacs of
      succeeding segments are serially homologous. The basal parts of appendage anlagen
      cover each sternum in the first to ninth abdominal segments to form coxites,
      which are therefore appendicular in origin. The basal part of the cercus also
      covers the ventral and lateral surfaces of the eleventh abdominal segment.

PMID- 30119588
TI  - Interdigital webbing and skin morphology in the neotropical salamander genus
      Bolitoglossa (amphibia; plethodontidae).
AB  - Arboreal salamanders of the Neotropical genus Bolitoglossa are characterized by
      palmate, fully webbed feet. The feet act as adhesive structures enabling the
      salamanders to cling to smooth surfaces. Scanning electron microscopy of skin
      epithelium and light microscopy of serial sections show exceptionally smooth cell
      surfaces and increased numbers of mucous glands on the soles of the feet. These
      features enhance the abilities of the feet to adhere by means of surface tension
      and suction. They are part of a set of morphological characteristics that may
      have been produced as a result of paedomorphosis.

PMID- 30119589
TI  - Fiber type composition and postmetamorphic growth of anuran hindlimb muscles.
AB  - Fiber type composition distinguished by the level of succinic dehydrogenase, mean
      fiber diameter, and fiber number were determined for the gracilis major and
      sartorius in ontogenetic series of the anurans Rana pipiens, Bufo americanus, and
      Xenopus laevis to characterize muscle composition and mode of muscle growth. A
      correlation can be made between the respective locomotor mode of these anurans,
      their activity physiology, and the fiber type composition of the propulsive
      muscles. R. pipiens and X. laevis have hindlimb muscles composed primarily of
      fast-twitch, fast-fatiguing type 1 fibers. B. americanus's muscles are composed
      of slow-twitch, slow-fatiguing type 2 and type 3 fibers. Fiber typing is
      apparently useful in explaining interspecific anuran locomotor capability
      previously difficult to correlate with body shape. Fiber typing also affords an
      explantion for reported variations in metabolism during strenuous activity.
      Postmetamorphically, anuran muscles grow by a combination of hyperplasia and
      hypertrophy, but the percent fiber type composition remains unchanged. In R.
      pipiens and X. laevis, the muscles grow primarily by hypertrophy with the
      addition of relatively fewer fibers. The converse is true for B. americanus. In
      all three species the combinations result in strong positive allometric increases
      in muscle cross section. Anuran muscle growth is similar to that reported for
      fish and different from that associated with mammals.

PMID- 30119590
TI  - Involvement of actin and Na+ -K+ ATPase in urine formation of the freshwater
      pulmonate Helisoma.
AB  - The site and process of urine formation in the renopericardial system of Helisoma
      have been investigated. Osmotic pressure and protein content of hemolymph from
      the heart, pericardial fluid from the pericardial cavity, prourine from the
      kidney sac, and urine from the ureter have been determined. Osmotic pressure is
      equal in hemolymph, pericardial fluid, and prourine, but less in urine. Protein
      content is similar in hemolymph and pericardial fluid, but much less in prourine
      and urine. Hemoglobin molecules are present in hemolymph and pericardial fluid
      but not in prourine. It is suggested that in Helisoma the kidney sac is the site
      of prourine formation, and prourine is an ultrafiltrate of hemolymph. The kidney
      epithelial cells contain 6- to 7-nm microfilaments which react with heavy
      meromyosin producing unidirectional arrowheads. Numerous actin filaments are
      present in the vicinity of the lateral cell membranes and basal processes. It is
      possible that the actin filaments regulate the extracellular spaces for prourine
      passage. It is postulated that the actin-rich kidney epithelium may generate
      hydrostatic pressure for ultrafiltration. Na+ -K+ ATPase is located on the
      luminal side of the kidney epithelium, which may regulate intracellular fluid
      level of the kidney epithelial cells, and thereby regulate their cell volume.
      Thus Na+ -K+ ATPase may be involved in the regulation of extracellular spaces in
      kidney epithelial cells. The enzyme may participate in the production of
      hyposmotic urine.

PMID- 30119591
TI  - Hormone dependent changes in the apical connective tissue during early stages of
      forelimb regeneration in the hypophysectomized newt, Notophthalmus viridescens.
AB  - When a newt is hypophysectomized prior to or at the time of forelimb amputation a
      dermal barrier eventually forms between the apical cap of epithelium and the
      underlying mesenchymal tissues, and the typical regeneration response is
      transformed to a wound-healing morphology. When hypophysectomized newts are
      injected on continuous alternate days beginning either at the time of amputation
      or following a fifteen-day delay, with either growth hormone (GH) or prolactin in
      combination with thyroxine (PLT4 ), normal regeneration occurs. Our experiment
      was designed to examine critically the early changes occurring in apical
      connective tissue that had been allowed to form as a consequence of
      hypophysectomy prior to forelimb amputation. Adult newts were hypophysectomized
      and five days later both forelimbs were amputated distal to the elbow. Following
      a delay of eight days, to permit the formation of connective tissue beneath the
      apical epithelium, they were injected intraperitoneally on successive alternate
      days with GH or with PL in combination with T4 in the aquarium water. The apical
      connective tissue of the limb stumps underwent a progressive erosion and became
      discontinuous by day 4. The limb morphology of hypophysectomized newts receiving
      ACTH or PL or maintained in thyroxine was virtually identical to sham-injected
      hypophysectomized controls. It appears that an initial effect of GH or PLT4
      therapy is to establish the epithelial-mesenchymal interface that previously has
      been suggested to be a requisite for the regenerative event.

PMID- 30119592
TI  - Foot of two-toed sloths: Its anatomy and potential uses relative to size of
      support.
AB  - Feet of two-toed sloths (Choloepus) are long, narrow, hook-like appendages with
      only three functional digits, numbers II, III, and IV; Rays I and V are
      represented by metatarsals. Proximal phalanges of complete digits are little more
      than proximal and distal articulating surfaces. All interphalangeal joints are
      restricted, by interlocking surfaces, to flexion and extension. Ankle and
      transverse tarsal joints, however, allow extreme flexion and inversion of foot.
      Powerful digital flexion is augmented by several muscles from extensor
      compartment of leg. Intrinsic foot musculature is reduced to flexors and
      extensors but these, with the exception of lumbricals, are large and well
      developed. Choloepus uses its feet much like hooks with distal phalanges and
      covering claws forming the "hook" element. These hook-like appendages are
      seemingly best suited for supports less than 50 mm in diameter suggesting that
      two-toed sloths may prefer supports of this size in their natural habitat.

PMID- 30119593
TI  - Experimental regeneration of the caudal skeleton of the glass knifefish,
      Eigenmannia virescens (Rhamphichthydae, Gymnotoidei).
AB  - This paper describes the regeneration of the caudal axial skeleton after
      amputation of the tail, including about 20 vertebrae, in the gymnotoid fish
      Eigenmannia virescens. Seven days after amputation, a regeneration blastema
      developed and soft tissues degenerated. A cylinder of cartilage developed at the
      end of the notochord. When this cartilage was about 10 mm long (21 days),
      perichondral ossification began. The cartilage continued to elongate and
      ossification increased while osteoclasts began to destroy the cartilage
      ventrally. Finally, a bony rod formed and at its tip the cartilage persisted as a
      rod, 2 to 3 mm long. The anal fin also regenerated: Endoskeletal cartilage
      developed first, following by differentiation of the lepidotrichia, and finally
      ossification of the endoskeleton.

PMID- 30119596
TI  - T-Probe: An Integrated Microscale Device for Online In Situ Single Cell Analysis
      and Metabolic Profiling Using Mass Spectrometry.
AB  - The exploration of single cells reveals cell heterogeneity and biological
      principle of cellular metabolism. Although a number of mass spectrometry (MS)
      based single cell MS (SCMS) techniques have been dedicatedly developed with high
      efficiency and sensitivity, limitations still exist. In this work, we introduced
      a microscale multifunctional device, the T-probe, which integrates cellular
      contents extraction and immediate ionization, to implement online in situ SCMS
      analysis at ambient conditions with minimal sample preparation. With high
      sensitivity and reproducibility, the T-probe was employed for MS analysis of
      single HeLa cells under control and anticancer drug treatment conditions.
      Intracellular species and xenobiotic metabolites were detected, and changes of
      cellular metabolic profiles induced by drug treatment were measured. Combining
      SCMS experiments with statistical data analyses, including Orthogonal Partial
      Least Squares-Discriminant Analysis (OPLS-DA) and two-sample t-test, we provided
      biological insights into cellular metabolic response to drug treatment. Online
      MS/MS analysis was conducted at single cell level to identify species of
      interest, including endogenous metabolites and the drug compound. Using the T
      probe SCMS technique combined with comprehensive data analyses, we provide an
      approach to understanding cellular metabolism and evaluate chemotherapies at the
      single cell level.

PMID- 30119594
TI  - Reference values of anthropometric measurementsin healthy late preterm and term
      infants
AB  - Background/aim: Geographical  distribution,  ethnicity,  and  other 
      socioeconomic  factors  may  affect  anthropometric  measurements,  and  for 
      that  reason  each  society  should  determine  their  own  measurements 
      accounting  for  those  factors.  In  this  study,  we  aimed  to  determine the
      anthropometric measurements of healthy late preterm and term infants to compare
      the results with other national and international studies. Materials and methods:
      This  sectional  study  was  carried  out  among  1197  infants  born  with  a 
      gestational  age  of  >=35  weeks.  Chest  circumference, ear length, foot
      length, palmar length, middle finger length, philtrum distance, inner and outer
      canthal distances, and palpebral fissure length were measured in the first 24 h
      of life. Results: All measurements of late preterm infants were smaller than
      those of term infants (P ? 0.05). Compared with male infants, the chest
      circumference, ear length, foot length, palmar length, philtrum distance, and
      inner canthal distances of the female infants were lower (P ?0.05). No
      significant differences were found between male and female infants' middle finger
      length, outer canthal distance, and palpebral fissure length measurements.
      Percentile values for all measurements of 35-42-week male and female infants were
      described. Conclusion: These  measurements  of  male  and  female  infants  born 
      between  35  and  42  weeks  may  be  useful  for  early  detection  of 
      syndromes by detecting anatomical abnormalities in our population.

PMID- 30119597
TI  - Creation of a Sub-slab Soil Gas Cloud by an Indoor Air Source and Its Dissipation
      Following Source Removal.
AB  - It is accepted that indoor sources of volatile organic compounds can confound
      vapor intrusion (VI) pathway assessment. When they are discovered during pre
      sampling inspection, indoor sources are removed and air sampling is delayed, with
      the assumption that a few hours to a few days are sufficient for indoor source
      impacts to dissipate. This assumption was tested through the controlled release
      of SF6 and its monitoring in indoor air and soil gas at a study house over 2
      years. Results show that indoor sources generate subsurface soil gas clouds as a
      result of fluctuating direction in the exchange between soil gas and indoor air
      and that it may take days to weeks under natural conditions for a soil gas cloud
      beneath a building to dissipate following indoor source removal. The data also
      reveal temporal variability in indoor air and soil gas concentrations, long-term
      seasonal patterns, and dissipation of soil gas clouds over days to weeks
      following source removal. Preliminary modeling results for similar conditions are
      consistent field observations. If representative of other sites, these results
      suggest that a typical 1-3 day waiting period following indoor source removal may
      not be sufficient to avoid confounding data and erroneous conclusions regarding
      VI occurrence.

PMID- 30119595
TI  - The in vitro effect of antimicrobial photodynamic therapy onCandida and
      Staphylococcus biofilms
AB  - Background/aim: This study was designed to evaluate the effect of antimicrobial
      photodynamic treatment (APDT) in a biofilm model using combinations of various
      dyes (rose bengal, riboflavin, and methylene blue) as photosensitizers and light
      sources (LED and UVA) against staphylococcal and candidal biofilms. Materials and
      methods: Sterile  microtiter  plates  were  used  for  the  development  and 
      quantification  of  the  biofilms.  APDT  was  carried  out  using  combinations 
      of  the  light  sources  and  dyes.  The  percentage  of  the  growth  inhibition
      was  then  calculated  using  a  spectrophotometer. The broth media in the wells
      were aspirated, wells were stained with crystal violet, and optical density
      values were measured spectrophotometrically. SEM analysis of the impact of APDT
      on bacterial and fungal biofilms was also performed. Results: The experiments
      showed that the most efficacious combination was red LED + methylene blue against
      both staphylococcal and candidal biofilms. A marked inhibition (45.4%) was
      detected on both C. albicans and C. parapsilosis biofilms. Red LED + methylene
      blue was also effective on S. aureus and S. epidermidis biofilms. SEM images
      suggested that the number of adherent cells and biofilm mass were markedly
      reduced after APDT treatment. Conclusion: Although the results of this study
      indicated the in vitro efficacy of APDT, it might also be a promising technique
      for the control of biofilm growth within intravenous catheters.

PMID- 30119598
TI  - Neutron Scattering Reveals Water Confined in a Watertight Bilayer Vesicle.
AB  - Water molecules confined in a nanocavity possess distinctly different
      characteristics from those in bulk, yet the preparation of such nanocavities is
      still a major experimental challenge. We report here a self-assembled vesicle of
      an anionic perfluoroalkylated [60]fullerene, unique for its outstanding stability
      and water tightness, containing water not bound to the membranes. Small-angle
      neutron scattering revealed that a vesicle of 14 nm outer radius contains a 2 nm
      thick fullerene bilayer, inside of which is a 3 nm thick membrane-bound water and
      unbound water in the 4 nm innermost cavity. The vesicle shows astonishingly low
      water permeability that is 6 to 9 orders of magnitude smaller than that of a
      lipid vesicle. As a result, a single vesicle isolated on a substrate can retain
      the interior water in air or even under high vacuum, indicating that the vesicle
      cavity provides a new tool for physicochemical studies of confined water as well
      as ions and molecules dissolved in it.

PMID- 30119599
TI  - Engineering Riboswitches in Vivo Using Dual Genetic Selection and Fluorescence
      Activated Cell Sorting.
AB  - Riboswitches, noncoding RNAs that bind a small molecule effector to control gene
      expression at the level of transcription or translation, are uniquely suited to
      meet challenges in synthetic biology. To expand the limited set of existing
      riboswitches, we developed a riboswitch discovery platform that couples dual
      genetic selection and fluorescence-activated cell sorting to identify novel
      riboswitches from a 108 random-sequence library in which the aptamer domain of
      the ThiM#2 riboswitch was replaced with an N40 sequence. In a proof-of-principle
      validation, we identified novel riboswitches for the small molecule theophylline.
      Our best riboswitch (Hit 3-5) displays 2.3-fold activation of downstream gene
      expression in the presence of theophylline. Random mutagenesis of Hit 3-5,
      coupled with selections and screens, afforded improved riboswitches displaying
      nearly 3-fold activation. To the best of our knowledge, this is the first report
      of in vivo directed evolution of an aptamer domain to generate a functional
      riboswitch.

PMID- 30119600
TI  - Selective Monodefluorination and Wittig Functionalization of gem-Difluoromethyl
      Groups to Generate Monofluoroalkenes.
AB  - Monodefluorination of gem-difluoromethyl groups is achieved using a frustrated
      Lewis pair (FLP) approach. Triarylphosphines and group 13 Lewis acids were
      surveyed as FLP components, with the combination of P( o-Tol)3 and B(C6F5)3 found
      to provide the best results, although the reaction is feasible with more
      economical components (PPh3 and BF3.OEt2). The alpha-fluoroalkylphosphonium
      products arising from the reaction were of lower activity, in regard to further
      fluoride abstraction, as compared to difluoride starting materials, leading to
      highly selective monodefluorination. The activated substrates were subject to
      Wittig reaction protocols to generate a variety of monofluoroalkenes in moderate
      to high yields.

PMID- 30119601
TI  - Evaluating the Impact of Neighborhood Characteristics on Differences between
      Residential and Mobility-Based Exposures to Outdoor Air Pollution.
AB  - Epidemiological studies often assign outdoor air pollution concentrations to
      residential locations without accounting for mobility patterns. In this study, we
      examined how neighborhood characteristics may influence differences in exposure
      assessments between outdoor residential concentrations and mobility-based
      exposures. To do this, we linked residential location and mobility data to
      exposure surfaces for NO2, PM2.5, and ultrafine particles in Montreal, Canada for
      5452 people in 2016. Mobility data were collected using the MTL Trajet smartphone
      application (mean: 16 days/subject). Generalized additive models were used to
      identify important neighborhood predictors of differences between residential and
      mobility-based exposures and included residential distances to highways, traffic
      counts within 500 m of the residence, neighborhood walkability, median income,
      and unemployment rate. Final models including these parameters provided unbiased
      estimates of differences between residential and mobility-based exposures with
      small root-mean-square error values in 10-fold cross validation samples. In
      general, our findings suggest that differences between residential and mobility
      based exposures are not evenly distributed across cities and are greater for
      pollutants with higher spatial variability like NO2. It may be possible to use
      neighborhood characteristics to predict the magnitude and direction of this error
      to better understand its likely impact on risk estimates in epidemiological
      analyses.

PMID- 30119602
TI  - Mitigating Greenhouse Gas and Ammonia Emissions from Beef Cattle Feedlot
      Production: A System Meta-Analysis.
AB  - Beef cattle production systems are the largest contributors of greenhouse gas
      (GHG) and ammonia (NH3) emissions in the livestock industry. Here, we present the
      first meta-analysis and integrated assessment of gaseous emissions and mitigation
      potentials for a typical beef cattle feedlot system, including methane (CH4),
      nitrous oxide (N2O), and NH3 losses from enteric fermentation and manure
      management based on data from 104 studies. A total of 14 integrated emission
      factors (EF) and the mitigation efficiencies (ME) of 17 available options were
      provided. The estimated GHG and NH3 emissions from the baseline feedlot system
      were 2786 +/- 108 kg carbon dioxide equivalents (CO2-eq) per animal unit (AU) per
      year and 49.1 +/- 1.5 kg NH3 AU-1 year-1, respectively. Enteric CH4 fermentation
      and manure on the feedlot contributed 67.5% and 80.8% of the total system GHG and
      NH3 emissions, respectively. The highest ME values were found for lipid additives
      for enteric CH4 fermentation and urease inhibitor additives (UI) for NH3
      emissions from manure on the feedlot, being -14.9% ( p < 0.05) and -59.5% ( p <
      0.001), respectively. The recommended mitigation combinations of a low-crude
      protein (CP) diet and a UI additive for manure on the feedlot could reduce the
      GHG of the system by 4.9% and NH3 by 50.9%. The results of this study have
      important implications for developing sustainable beef cattle feedlot systems
      from the viewpoint of GHG and NH3 mitigation.

PMID- 30119603
TI  - Multiple Cross-Linking of a Small Peptide to Form a Size Tunable Biopolymer with
      Efficient Cell Adhesion and Proliferation Property.
AB  - Development of biocompatible polymeric systems capable of cell adhesion and
      proliferation is a challenging task. Proper cross-linking of small cell adhesive
      peptide sequences is useful in this respect as it provides the inherent nontoxic
      environment as well as the cross-linked polymeric network to the cells for
      adhesion and proliferation. A multiple cross-linking strategy is applied to
      create a peptide-based cross-linked polymer. Covalent linkage through disulfide
      bond formation, supramolecular linkage using homoternary complexation by CB[8],
      and enzymatic cross-linking by HRP-mediated dimerization of tyrosine are used to
      prepare the cross-linked, peptide-based polymer decorated with cell-adhesive RGDS
      sequence. The supramolecular cross-linking via CB[8] provided stability as well
      as brings the RGDS sequences at the surface of the polymer particles. The order
      of cross-linking allowed to fine-tune the particle size of the polymer and
      polymer particles of wide range (200-1000 nm) can be prepared by varying the
      order. The cross-linked polymer particles (P1 and P2) were found to be stable at
      wide range of temperature and pH. Moreover, as intended, the polymer was
      noncytotoxic in nature and showed efficient cell adhesion and proliferation
      property, which can be used for further biological applications.

PMID- 30119604
TI  - Evaluation of a Passive Sampling Method for Long-Term Continuous Monitoring of
      Volatile Organic Compounds in Urban Environments.
AB  - Environmental Protection Agency Method 325 was developed for continuous passive
      monitoring of volatile organic compounds (VOCs), particularly benzene, at
      petroleum refinery fencelines. In this work, a modified version of the method was
      evaluated at an Ontario near-road research station in winter to assess its
      suitability for urban air quality monitoring. Samples were collected at 24 hour
      and 14 day resolution to investigate accuracy for different exposure times. Tubes
      were analyzed by thermal desorption-gas chromatography-mass spectrometry, and 11
      VOCs were quantified, including aromatic air toxics. The same VOCs were
      simultaneously monitored using traditional canister sampling for comparison, and
      a subset of four were also monitored using a novel miniature gas chromatograph.
      Good agreement (within 10%) was observed between the 14 day passive tube samples
      and the canister samples for benzene. However, field-calibrated uptake rates were
      required to correct passive tube concentrations for less volatile aromatics.
      Passive tube deployment and analysis is inexpensive; sampling does not require
      power, and accurate measurements of benzene are demonstrated here for an urban
      environment. The method is expected to be advantageous for the generation of long
      term continuous benzene datasets suitable for epidemiological research with
      greater spatial coverage than is currently available using traditional monitoring
      techniques.

PMID- 30119605
TI  - Dual Roles for Potassium Hydride in Haloarene Reduction: CSNAr and Single
      Electron Transfer Reduction via Organic Electron Donors Formed in Benzene.
AB  - Potassium hydride behaves uniquely and differently than sodium hydride toward
      aryl halides. Its reactions with a range of haloarenes, including designed 2,6
      dialkylhaloarenes, were studied in THF and in benzene. In THF, evidence supports
      concerted nucleophilic aromatic substitution, CSNAr, and the mechanism originally
      proposed by Pierre et al. is now validated through DFT studies. In benzene,
      besides this pathway, strong evidence for single electron transfer chemistry is
      reported. Experimental observations and DFT studies lead us to propose organic
      super electron donor generation to initiate BHAS (base-promoted homolytic
      aromatic substitution) cycles. Organic donor formation originates from
      deprotonation of benzene by KH; attack on benzene by the resulting
      phenylpotassium generates phenylcyclohexadienylpotassium that can undergo (i)
      deprotonation to form an organic super electron donor or (ii) hydride loss to
      afford biphenyl. Until now, BHAS reactions have been triggered by reaction of a
      base, MO tBu (M = K, Na), with many different types of organic additive, all
      containing heteroatoms (N or O or S) that enhance their acidity and place them
      within range of MO tBu as a base. This paper shows that with the stronger base,
      KH, even a hydrocarbon (benzene) can be converted into an electron-donating
      initiator.

PMID- 30119607
TI  - The LDA-1/2 Method Applied to Atoms and Molecules.
AB  - The LDA-1/2 method evaluates ionization potentials as the energy of the highest
      occupied molecular orbitals (HOMOs) at half occupation. It has proven to be a
      viable approach for calculating band gaps of semiconductors. To address its
      accuracy for finite systems, we apply LDA-1/2 to the atoms and molecules of the
      GW100 test set. The obtained HOMO energies are validated against CCSD(T) data and
      the G0 W0 approach of many-body perturbation theory. The accuracy of LDA-1/2 and
      G0 W0 is found to be the same, where the latter is computationally much more
      involved. To get insight into the benefits and limitations of the LDA-1/2 method,
      we analyze the impact of each assumption made in deriving the methodology.

PMID- 30119606
TI  - Online Liquid Chromatography-Sheath-Flow Surface Enhanced Raman Detection of
      Phosphorylated Carbohydrates.
AB  - Online detection and quantification of three phosphorylated carbohydrate
      molecules: glucose 1-phosphate, glucose 6-phosphate, and fructose 6-phosphate was
      achieved by coupling sheath-flow surface enhanced Raman spectroscopy (SERS) to
      liquid chromatography. The presence of an alkanethiol (hexanethiol) self
      assembled monolayer adsorbed to a silver SERS-active substrate helps retain and
      concentrate the analytes of interest at the SERS substrate to improve the
      detection sensitivity significantly. Mixtures of 2 MUM of phosphorylated
      carbohydrates in pure water as well as in cell culture media were successfully
      separated by HPLC, with identification using the sheath-flow SERS detector. The
      quantification of each analyte was achieved using partial least-squares (PLS)
      regression analysis and acetonitrile in the mobile phases as an internal
      standard. These results illustrate the utility of sheath-flow SERS for molecular
      specific detection in complex biological samples appropriate for metabolomics and
      other applications.

PMID- 30119608
TI  - Zwitterionic Hydrogels Based on a Degradable Disulfide Carboxybetaine Cross
      Linker.
AB  - We report the synthesis of a zwitterionic carboxybetaine disulfide cross-linker
      (CBX-SS) and biodegradable poly(carboxybetaine) (PCB) hydrogels and nanocages
      (NCs) made using this cross-linker. The structure of CBX-SS combines zwitterionic
      carboxybetaine to confer nonfouling properties and a disulfide linkage to
      facilitate degradation. The physical, mechanical, and fouling characteristics of
      PCB hydrogels cross-linked with CBX-SS were investigated. Then, the degradation
      characteristics of CBX-SS-cross-linked hydrogels were evaluated through their
      weight loss and release of an encapsulated protein in a reducing environment.
      Furthermore, CBX-SS was applied to prepare degradable PCB NCs. Results show that
      encapsulating the highly immunogenic enzyme uricase in degradable PCB NCs
      eliminates or prevents an in vivo immune response to both the protein and
      polymer.

PMID- 30119610
TI  - Tunable Noble Metal Thin Films on Ga Alloys via Galvanic Replacement.
AB  - Room-temperature liquid metals such as GaInSn or EGaIn present the most
      attractive properties for soft and highly stretchable electronics. Recently,
      several methods have been investigated to functionalize the surface of the liquid
      metal via coatings and encapsulation. However, most can hardly be extended to
      other samples than droplets. In this study, we focus on the tunability of the
      process of galvanic replacement of Ga alloys with gold to form thin-film
      encapsulation. We characterized in-depth the obtainable composition and structure
      of a noble metal shell formed on the liquid metal via scanning electron
      microscopy, energy-dispersive X-ray, and topographic laser microscopy and
      highlighted the change in mechanism of galvanic replacement in different pH
      ranges. We showed the tunability of the surface morphology selection of different
      pH ranges, the solutions concentrations, and the reaction time. The adjustment of
      the pH of KAuBr4 solution to the preferential Ga2O3-free domain led to the
      successful formation of a sub-micrometer thin uniform coating with more than 60%
      of Au and reduced level of oxygen from 30% down to 10%. We finally demonstrated
      the effect of the coating composition on the electrical properties of the liquid
      metal using a simple and fast phase-drop measurement setup on the droplet and
      microchannels. A high correlation between the amount of noble metal deposited and
      the electrical properties of the droplets was demonstrated.

PMID- 30119611
TI  - Modulating Intracellular Ice Growth with Cell-Permeating Small-Molecule Ice
      Recrystallization Inhibitors.
AB  - Ice formation remains central to our understanding of the effects of low
      temperatures on the biological response of cells and tissues. The formation of
      ice inside of cells and the net increase in crystal size due to recrystallization
      during thawing is associated with a loss of cell viability during
      cryopreservation. Because small-molecule ice recrystallization inhibitors (IRIs)
      can control the growth of extracellular ice, we sought to investigate the ability
      of two aryl-glycoside-based IRIs to permeate into cells and control intracellular
      ice recrystallization. An interrupted graded freezing technique was used to
      evaluate the IRI permeation into human red blood cells (RBCs) and mitigate cell
      damage during freezing and thawing. The effect of IRIs on the intracellular
      growth of ice crystals in human umbilical vein endothelial cells (HUVECs) was
      visualized in real time under different thawing conditions using fluorescence
      cryomicroscopy. Adding an aryl glycoside to 15% glycerol significantly increased
      post-thaw RBC integrity by up to 55% during slow cooling compared with the 15%
      glycerol-only control group. The characteristics of the cryobiological behavior
      of the RBCs subjected to the interrupted graded freezing suggest that the aryl
      glycoside-based IRI is internalized into the RBCs. HUVECs treated with the IRIs
      were shown to retain a large number of small ice crystals during warming to high
      subzero temperatures and demonstrated a significant inhibition of intracellular
      ice recrystallization. Under slow thawing conditions, the aryl glycoside IRI p
      bromophenyl-beta-d-glucoside was shown to be most effective at inhibiting
      intracellular ice recrystallization. We demonstrate that IRIs are capable of
      internalizing into cells, altering the cryobiological response of cells to slow
      and rapid freezing and controlling intracellular ice recrystallization during
      freezing. We conclude that IRIs have tremendous potential as cryoprotectants for
      the preservation of cells and tissues at high subzero temperatures.

PMID- 30119609
TI  - Tuning Antisite Defect Density in Perovskite-BaLiF3 via Cycling between Ball
      Milling and Heating.
AB  - The defect density of a material is central to its properties. Here, we show,
      employing EXAFS measurements and MD simulation, how the Ba-Li antisite defect
      density of perovskite-structured BaLiF3 nanoparticles can be tuned. In
      particular, we show that ball milling reduces the defect content. Conversely,
      thermal annealing increases the defect density. The work represents a first step
      toward tailoring the properties of a material via defect tuning postsynthesis.

PMID- 30119612
TI  - Lipid Membrane Interactions of the Cationic Antimicrobial Peptide Chimeras
      Melimine and Cys-Melimine.
AB  - Melimine and its derivatives are synthetic chimeric antimicrobial agents based on
      protamine and melittin. The binding of solubilized melimine and its derivative,
      with a cysteine on N-terminus, (cys-melimine) on tethered bilayer lipid membranes
      (tBLMs) was examined using ac electrical impedance spectroscopy. The addition of
      melimine and cys-melimine initially increased membrane conduction, which
      subsequently falls over time. The results were obtained for tBLMs comprising
      zwitterionic phosphatidylcholine, anionic phosphatidylglycerol, or tBLMs made
      using purified lipids from Escherichia coli. The effect on conduction is more
      marked with the cysteine variant than the noncysteine variant. The variation in
      membrane conduction most probably arises from individual melimines inducing
      increased ionic permeability, which is then reduced as the melimines aggregate
      and phase-separate within the membrane. The actions of these antimicrobials are
      modeled in terms of altering the critical packing parameter (CPP) of the
      membranes. The variations in the peptide length of cys-melimine were compared
      with a truncated version of the peptide, cys-mel4. The results suggest that the
      smaller molecule impacts the membrane by a mechanism that increases the average
      CPP, reducing membrane conduction. Alternatively, an uncharged alanine
      replacement version of melimine still produced an increase in membrane
      conduction, further supporting the CPP model of geometry-induced toroidal pore
      alterations. All the data were then compared to their antimicrobial effectiveness
      for the Gram-positive and Gram-negative strains of bacteria, and their fusogenic
      properties were examined using dynamic light scattering in 1-oleoyl-2-hydroxy- sn
      glycero-3-phosphocholine lipid spheroids. We conclude that a degree of
      correlation exists between the antimicrobial effectiveness of the peptides
      studied here and their modulation of membrane conductivity.

PMID- 30119613
TI  - Inorganic/Organic Double-Network Ion Gels with Partially Developed Silica
      Particle Network.
AB  - Tough inorganic/organic composite network gels consisting of a partially
      developed silica-particle network and a large amount of an ionic liquid, named
      micro-double-network (MU-DN) ion gel, are fabricated via two methods. One is a
      one-pot/one-step process conducted using a simultaneous network formation via sol
      gel reaction of tetraethyl orthosilicate and free radical polymerization of N, N
      dimethylacrylamide in an ionic liquid. When the network formation rates of the
      inorganic and organic networks are almost the same, the MU-DN structure is
      formed. The second method is simpler and involved the use of silica nanoparticles
      as the starting material. By controlling the dispersion state of the silica
      nanoparticles in an ionic liquid, the MU-DN structure is formed. In both MU-DN
      ion gels, silica nanoparticles partially aggregate and form network-like
      clusters. When a large deformation is induced in the MU-DN ion gels, the silica
      particle clusters rupture and dissipate the loaded energy. The fracture stress
      and Young's modulus of the MU-DN ion gel increase as the size of the silica
      nanoparticles decreases. The increment in the mechanical strength would have been
      caused by the increase in the total van der Waals attraction forces and the total
      number of hydrogen bonding in the silica-particle networks.

PMID- 30119614
TI  - Active Students Are Healthier and Happier Than Their Inactive Peers: The Results
      of a Large Representative Cross-Sectional Study of University Students in
      Ireland.
AB  - BACKGROUND: Time spent in university represents a period of transition and may be
      an appropriate time to promote physical activity among young adults. The aim of
      this study was to assess participation of university students in sport and
      physical activity in Ireland and to explore the association between physical
      activity and perceptions of overall health, mental health, and happiness.
      METHODS: The Student Activity and Sport Study Ireland was a cross-sectional
      online survey among a representative sample (n = 8122) of university students in
      Ireland. Binary logistic regressions were performed to examine associations
      between self-reported physical activity and gender (predictor variables) and
      individual perceptions of overall health, mental health, and happiness (binary
      outcomes). RESULTS: Only 64.3% of respondents met the recommended level of 150
      minutes of moderate to vigorous physical activity per week with males
      significantly more active than females (72.1% vs 57.8% meeting guidelines). Those
      meeting physical activity guidelines were more likely to report greater overall
      health and higher mental health and happiness scores compared with their inactive
      peers. CONCLUSIONS: Active students enjoy better health (overall and mental) and
      are happier than their inactive peers. This provides a clear rationale for
      providing students with opportunities to be active at university. The data
      provide a baseline to monitor changes in physical activity patterns.

PMID- 30119615
TI  - Individual Histologic Lesions and Composite Scores in Implant Biopsies Affect
      Short-Term and Long-Term Kidney Allograft Function.
AB  - OBJECTIVES: Our aim was to evaluate which histologic lesions in a donor kidney
      were associated with graft function up to 5 years and with its dynamics.
      MATERIALS AND METHODS: We retrospectively investigated the association between
      acute and chronic individual histologic lesions and composite scores in
      preimplant and postreperfusion biopsies from deceased-donor (n = 101) and living
      donor (n = 29) kidneys with initial graft function and function at discharge, at
      6 months, and at 5 years and slopes of estimated glomerular filtration rate from
      discharge to 6 months and from 6 months to 5 years. RESULTS: A high frequency of
      chronic and acute histologic lesions in donor kidneys is characteristic of our
      population of donors with high cardiovascular risk. Glomerulitis in preimplant
      biopsies predicted delayed graft function. Arteriolar hyalinosis predicted
      impaired initial graft function. Arteriolar hyalinosis and arteriosclerosis both
      predicted lower estimated glomerular filtration rate at discharge and >= 25% drop
      in function after 6 months. Glomerulosclerosis affected the estimated glomerular
      filtration rate at discharge and at 6 months; percentage of changed glomeruli
      predicted lower function at discharge and at 5 years. Glomerular thrombi in
      preimplant and postreperfusion biopsies predicted negative slope in estimated
      glomerular filtration rate from discharge to 6 months and a >= 25% drop in
      function after 6 months, respectively. Fibrinoid necrosis in glomeruli in
      preimplant biopsies predicted decline in function of >= 5 mL/min/1.73m2 every
      year after 6 months. Chronic and total preimplant and posttransplant Banff scores
      predicted lower estimated glomerular filtration rate at discharge and at 6
      months, with >= 25% drop in function after 6 months. CONCLUSIONS: Intraoperative
      biopsies are important in identifying patients at risk for worse graft function,
      especially concerning absence of gain of function early after transplant and loss
      of function late after transplant.

PMID- 30119617
TI  - Posttransplant Malignancies in Adult Renal and Hepatic Transplant Patients.
AB  - OBJECTIVES: The risk of some cancer types increases after organ transplant
      compared with that shown in the general population; this has been well documented
      in clinical studies. With patients having longer survival and with the higher
      number of transplant procedures, cancer is an increasing health concern at high
      volume transplant centers. Malignancy has an important effect on short- and long
      term graft and patient survival. In this study, we evaluated cancer frequency
      during transplant patient follow-up. MATERIALS AND METHODS: This single-center
      retrospective study included patients who underwent solid-organ transplant at the
      Baskent University Medical Faculty Hospital from 1997 to 2017. Renal and hepatic
      transplant patients older than 16 years at the time of transplant and diagnosed
      with cancer after transplant were included the study. In total, 1176 of 2018
      renal transplant recipients and 274 of 548 hepatic transplant recipients met the
      inclusion criteria. RESULTS: We determined that 52 of 1176 renal transplant
      (4.5%) and 9 of 274 hepatic transplant patients (3.3%) developed posttransplant
      cancer during follow-up. Of 61 total patients with cancer posttransplant, 44 were
      males (72.1%) and 17 were females (27.9%), with median age at transplant of 39.2
      years. Overall, the incidence of cancer in transplant recipients was 4.2%. The
      most frequent cancers were basal and squamous skin cancers, which were seen in 18
      patients (29%), and Kaposi sarcoma, which was seen in 11 patients (18%). Of the
      61 patients who developed cancer, 43 (70%) were still alive at the time of this
      study. CONCLUSIONS: Despite recent positive developments in the use of
      immunosuppressive drugs, posttransplant malignancy is still a health problem.
      Fortunately, most cancers in this patient group have good prognosis and can be
      cured by surgical resection. Transplant physicians should aim for early detection
      of these diseases.

PMID- 30119616
TI  - Heat Stroke as a Cause of Liver Failure and Evaluation of Liver Transplant.
AB  - Heat stroke is a multiple organ dysfunction syndrome of poorly understood
      pathogenesis. Exertional heat stroke with acute liver failure is a rarely
      reported condition. Liver transplant has been recommended as treatment in cases
      of severe liver dysfunction; however, there are only 5 described cases of long
      term survival after this procedure in patients with heat stroke. Here, we present
      2 cases of young athletes who developed heat stroke. Both patients developed
      acute liver failure and were listed for liver transplant. Liver function tests of
      one patient improved, and he was discharged on postoperative day 13. The other
      patient showed no signs of improvement and liver biopsy showed massive necrosis.
      The patient underwent combined kidney-liver transplant and was discharged on
      postoperative day 17. After a follow-up of longer than 6 years, both patients are
      doing well with normal liver function and no neurologic sequelae. We also
      reviewed all published cases of hepatic failure associated with heat stroke and
      found 9 published cases of liver transplant for heat stroke in the English
      literature. Conservative management appears to be justified in heat stroke
      associated liver failure, even in the presence of accepted criteria for emergency
      liver transplant.

PMID- 30119618
TI  - Single-Center Experience With Liver Transplant Using Donors With Very High
      Transaminase Levels.
AB  - OBJECTIVES: Elevation of transaminases has been used as a marker of hepatic
      ischemic injury and as a crucial parameter for liver graft assessment. However,
      analysis of serum transaminases has limitations regarding the quantitative
      assessment of liver necrosis and is not a reliable predictor of outcomes.
      MATERIALS AND METHODS: We retrospectively reviewed the medical records of all
      liver transplants (N = 238) performed at the UMass Memorial Medical Center from
      2009 to 2013. RESULTS: Fourteen liver grafts showed high peak aminotransferases
      alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at > 1000
      U/L. This high aminotransferase group was compared with 224 donors with low
      transaminase levels (ALT/AST < 1000 U/L). The high transaminase donors had a
      median peak AST level of 3216 U/L (range, 1823-13?030 U/L) and ALT level of 2677
      U/L (range, 812-7080 U/L). The high transaminase donors showed higher levels of
      lactate dehydrogenase, international normalized ratio, total bilirubin, and gamma
      glutamyltransferase compared with low transaminase donors; however, only lactate
      dehydrogenase results reached statistical significance. None of the grafts from
      the high transaminase donors showed primary nonfunction. Three-year graft and
      patient survival rates were similar in both groups (75% vs 80% [P = .48] and 72%
      vs 82% [P = .33], respectively). In an analysis of the discard rate of livers
      over a 10-year period in the United States using the Scientific Registry of
      Transplant Recipients database, the discard rate of livers with high
      aminotransferase levels was 69.14% compared with 22.23% for livers with low
      transaminase levels. CONCLUSIONS: Liver grafts from donors with high transaminase
      levels can lead to clinical results that are similar to liver grafts from donors
      who had lower peak transaminase levels.

PMID- 30119619
TI  - Prevalence of Incidental Findings on Multidetector Computed Tomography in
      Potential Nephrectomy Donors: A Prospective Observational Study.
AB  - OBJECTIVES: Prospective renal donors are a select population of healthy
      individuals who have been thoroughly screened for significant comorbidities
      before they undergo multidetector computed tomography. Our aim was to determine
      the prevalence of incidental findings on preoperative multidetector computed
      tomography in a healthy cohort of potential living donors for kidney transplant.
      MATERIALS AND METHODS: A prospective study was performed of prospective living
      kidney transplant donors at a national kidney transplant center. Study inclusion
      criteria were all potential kidney donors who underwent multidetector computed
      tomography during the living-donor assessment process over a 5-year period
      (January 2012 to 2017). RESULTS: Our cohort included 375 potential living donors
      who had multidetector computed tomography; mean age was 44.33 years (range, 21
      71.5 y). In total, there were 228 incidental findings identified in 158
      individuals. Of the 375 potential donors, 193 (51%) proceeded to living donor
      nephrectomy. On multidetector computed tomography, 97 incidental findings were
      identified in the donor cohort versus 131 in the cohort that did not proceed to
      donation. Bosniak 1 renal cysts were the most common incidental finding (n = 46)
      followed by liver cysts < 1.5 cm (n = 42) and urinary tract calculi (n = 21).
      There was 1 incidentally detected pathologically proven malignancy. CONCLUSIONS:
      A variety of incidentally detected lesions of moderate to high importance were
      detected in this healthy donor cohort. Individuals undergoing assessment with
      multidetector computed tomography for living donor nephrectomy should be
      counseled on medical, financial, and psychological implications of incidentally
      detected lesions during the kidney transplant evaluation process.

PMID- 30119620
TI  - Hyperventilation Syndrome and Sustained Hyperchloremia After Kidney Transplant:
      Time-Sequence Swing of Acid-Base Interpretation.
AB  - An interaction between regained renal function in a transplanted kidney and
      hyperventilation syndrome may interfere with correct diagnosis of acid-base
      status in patients with preoperative nongap acidosis. Here, we present a patient
      with glomerular nephritis and hyperchloremia who underwent kidney transplant.
      Progressively increasing bicarbonate reabsorption by the renal graft, which
      thereby changed the arterial carbon dioxide tension-to-bicarbonate ratio,
      resulted in a time-sequence swing of an acid-base interpretation despite
      persistent mixed respiratory alkalosis due to hyperventilation syndrome and
      nongap metabolic acidosis due to preexisting hyperchloremia. Specifically, the
      sequence was mixed primary metabolic acidosis and primary respiratory acidosis
      immediately after surgery, primary metabolic acidosis and secondary respiratory
      alkalosis on postoperative days 1 and 2, mixed primary hyperchloremic metabolic
      acidosis and primary respiratory alkalosis on postoperative day 3, and finally
      primary respiratory alkalosis and secondary hyperchloremic metabolic acidosis on
      postoperative day 7. This swing in the acid-base interpretation indicates that
      the acid-base imbalance described here does not fit the empirical relationship
      for calculating the expected bicarbonate or carbon dioxide tension value,
      suggesting that "correct" interpretation of acid-base status may not lead to
      "correct" diagnosis of acid-base status. It should be remembered that not every
      acid-base imbalance fits the empirical relationship.

PMID- 30119621
TI  - Living Liver Donor With Fasciola Hepatica: First Case Report in the Literature.
AB  - The major advantage of preoperative magnetic resonance cholangiopancreatography
      is that living liver donor candidates with complicated biliary tracts may not be
      exposed to unnecessary laparotomy. To the best of our knowledge, the case
      presented here features a condition so far not seen by the Liver Transplantation
      Society. A 27-year-old woman who presented to our clinic as a living liver donor
      candidate was evaluated but did not have a preoperative magnetic resonance
      cholangiopancreatography due to technical factors. After parenchymal transection,
      the right hepatic duct was incised just distal to the bifurcation when 8 fasciola
      hepatica parasites left the orifice of the remnant bile duct. The common bile
      duct was then irrigated, and the remnant bile duct orifice was closed, followed
      by a cholangiography, which showed no suspicious lesions in the biliary tracts.
      In addition, no suspicious lesions were identified during the postoperative
      cholangiography of the graft implanted in the recipient. The donor and recipient
      had postoperative enzyme-linked immunosorbent assay immunoglobulin G antibody
      titers of 12 and 4 U/mL (cutoff value = 10) for fasciola hepatica, respectively.
      Both the recipient and the donor received 2 doses of triclabendazole (10 mg/kg)
      during the postoperative period.

PMID- 30119622
TI  - Extent of third-order linkage disequilibrium in a composite line of Iberian pigs.
AB  - BACKGROUND: Previous studies on linkage disequilibrium have investigated second
      order linkage disequilibrium in animal and plant populations. The objective of
      this paper was to investigate the genome-wide levels of third order linkage
      disequilibrium in a composite line founded by admixture of four Iberian pig
      strains. A model for the generation of third order linkage disequilibrium by
      population admixture is proposed. A computer Expectation-Maximization algorithm
      is developed and applied to the estimation of third order linkage disequilibrium
      at inter- and intra-chromosomal level using 26,347 SNPs typed in 306 sows. The
      relationship of third order linkage disequilibrium with physical distance was
      investigated over 35 million triplets in SSC12. Basic and normalized estimates of
      inter and intra-chromosomal third order linkage disequilibrium are reported.
      RESULTS: Genome-wide analyses revealed that third order linkage disequilibrium is
      rather common among linked loci in this Iberian pig line. It is shown that
      population admixture of multiple populations may explain the observed levels of
      third order linkage disequilibrium although it could be generated by genetic
      drift. Third order linkage disequilibrium decreases rapidly up to 4 Mb and then
      declines slowly. The short distances between consecutive markers explain the
      maintenance of the observed third order linkage disequilibria levels when using a
      model incorporating the break-up of disequilibrium by recombination. Genome-wide
      testing also revealed that only 3.6% of the normalized estimates were different
      from 1, - 1, 0, or from a not well-defined situation in which there is only one
      possible value for the third order linkage disequilibrium parameter, given allele
      frequencies and pairwise linkage disequilibria parameters. CONCLUSIONS: Third
      order linkage disequilibrium is common among linked markers in the analyzed pig
      line and may have been generated by population admixture of multiple populations
      or by genetic drift. As with second order linkage disequilibrium, the absolute
      value of the third order linkage disequilibrium decreases with physical distance.
      Normalization of third order linkage disequilibrium should be avoided for closely
      linked bi-allelic loci.

PMID- 30119623
TI  - Obesity paradox in patients undergoing lung lobectomy - myth or reality?
AB  - BACKGROUND: The aim of the present study was to evaluate the impact of BMI on the
      short-term outcomes of patients undergoing lung lobectomy. METHODS: This was a
      retrospective clinical cohort study conducted in a single institution to assess
      the short-term outcomes of obese patients undergoing lung resection.
      Intraoperative and postoperative parameters were compared between the two study
      subgroups: obese (BMI >=30 kg/m2) and non-obese patients (BMI < 30 kg/m2).
      RESULTS: In total, 203 patients were enrolled in the study (70 obese and 133 non
      obese patients). Both study subgroups were comparable with regards to
      demographics, clinical data and surgical approach (thoracoscopy vs. thoracotomy).
      The surgery time was significantly longer in obese patients (p = 0.048). There
      was no difference in the frequency of intraoperative complications between the
      study subgroups (p = 0.635). The postoperative hospital stay was similar in both
      study subgroups (p = 0.366). A 30-day postoperative morbidity was higher in a
      subgroup of non-obese patients (33.8% vs. 21.7%), but the difference was not
      significant (p = 0.249). In the subgroup of non-obese patients, a higher
      frequency of mild and severe postoperative complications was observed. However,
      the differences between the study subgroups were not statistically significant
      due to the borderline p-value (p = 0.053). The 30-day postoperative mortality was
      comparable between obese and non-obese patients (p = 0.167). CONCLUSIONS: Obesity
      does not increase the incidence and severity of intraoperative and postoperative
      complications after lung lobectomy. Slightly better outcomes in obese patients
      indicate that obesity paradox might be a reality in patients undergoing lung
      resection.

PMID- 30119625
TI  - Interprofessional education between medical students and nurse practitioner
      students in a Global Health course.
AB  - BACKGROUND: Few global health experiences include intentionally-directed
      interprofessional training. We aim to prospectively evaluate the impact of a
      global health elective in facilitating interprofessional education (IPE) and
      promoting cultural sensitivity. METHODS: We included in our study, medical and
      nursing students who participated in the 2015 and 2016 cohorts of the Nicaragua
      Global Health course. The course consisted of a 12-week curriculum, and included
      an in-country immersion where students were organized into small-groups that
      participated in a variety of interprofessional activities. Students filled out
      pre- and post-course surveys. We performed quantitative analysis on numeric data
      and qualitative analysis on open-ended questions. RESULTS: Of 39 total students
      enrolled in the course, 26 (18 medical and 8 nursing students) participated in
      the study and filled out the pre- and post-course surveys. Mean competency scores
      increased for all questions between pre- and post-course surveys, and of these, 5
      of 7 reached statistical significance. Qualitative themes identified included: 1)
      the importance of understanding other team member's roles and relative strengths;
      2) the value provided by the breaking down of traditional power dynamics between
      clinicians. CONCLUSIONS: Global health experiences represent a unique and under
      utilized opportunity for facilitating IPE.

PMID- 30119624
TI  - Exploring reasoning mechanisms in ward rounds: a critical realist multiple case
      study.
AB  - BACKGROUND: Ward rounds are an important and ubiquitous element of hospital care
      with a history extending well over a century. Although originally intended as a
      means of educating medical trainees and junior doctors, over time they have
      become focused on supporting clinical practice. Surprisingly, given their
      ubiquity and importance, they are under-researched and inadequately understood.
      This study aims to contribute knowledge in human reasoning within medical teams,
      meeting a pressing need for research concerning the reasoning occurring in
      rounds. METHODS: The research reported here aimed to improve the understanding of
      ward round reasoning by conducting a critical realist case study exploring the
      collaborative group reasoning mechanisms in the ward rounds of two hospitals in
      Victoria, Australia. The data collection involved observing rounds, interviewing
      medical practitioners and holding focus group meetings. RESULTS: Nine group
      reasoning mechanisms concerning sharing, agreeing and recording information in
      the categories of information accumulation, sense-making and decision-making were
      identified, together forming a program theory of ward round reasoning. In
      addition, themes spanning across mechanisms were identified, further explaining
      ward round reasoning and suggesting avenues for future exploration. Themes
      included the use of various criteria, tensions involving mechanisms, time
      factors, medical roles and hierarchies. CONCLUSIONS: This paper contributes to
      the literature by representing rounds in a manner that strengthens understanding
      of the form of the group reasoning occurring within, thus supporting theory-based
      evaluation strategies, redesigned practices and training enhancements.

PMID- 30119626
TI  - Lignocellulose integration to 1G-ethanol process using filamentous fungi:
      fermentation prospects of edible strain of Neurospora intermedia.
AB  - BACKGROUND: Integration of first- and second-generation ethanol processes is one
      among the alternate approaches that efficiently address the current socio
      economic issues of the bioethanol sector. Edible filamentous fungus capable of
      utilizing pentoses from lignocelluloses and also possessing biomass application
      as potential animal feed component was used as the fermentation strain for the
      integration model. This study presents various fermentation aspects of using
      edible filamentous fungi in the integrated first and second generation ethanol
      process model. RESULTS: Fermentation of edible strain of N. intermedia on the
      integrated first and second-generation ethanol substrate (the mixture of dilute
      acid pretreated and enzymatically hydrolyzed wheat straw and thin stillage from
      the first-generation ethanol process), showed an ethanol yield maximum of 0.23 +/
      0.05 g/g dry substrate. The growth of fungal pellets in presence of fermentation
      inhibitors (such as acetic acid, HMF and furfural) resulted in about 11 to 45%
      increase in ethanol production as compared to filamentous forms, at similar
      growth conditions in the liquid straw hydrolysate. Fungal cultivations in the
      airlift reactor showed strong correlation with media viscosity, reaching a
      maximum of 209.8 +/- 3.7 cP and resulting in 18.2 +/- 1.3 g/L biomass during the
      growth phase of fungal pellets. CONCLUSION: N. intermedia fermentation showed
      high sensitivity to the dilute acid lignocellulose pretreatment process, with
      improved fermentation performance at milder acidic concentrations. The
      rheological examinations showed media viscosity to be the most critical factor
      influencing the oxygen transfer rate during the N. intermedia fermentation
      process. Mycelial pellet morphology showed better fermentation efficiency and
      high tolerance towards fermentation inhibitors.

PMID- 30119627
TI  - Development of a personalized diagnostic model for kidney stone disease tailored
      to acute care by integrating large clinical, demographics and laboratory data:
      the diagnostic acute care algorithm - kidney stones (DACA-KS).
AB  - BACKGROUND: Kidney stone (KS) disease has high, increasing prevalence in the
      United States and poses a massive economic burden. Diagnostics algorithms of KS
      only use a few variables with a limited sensitivity and specificity. In this
      study, we tested a big data approach to infer and validate a 'multi-domain'
      personalized diagnostic acute care algorithm for KS (DACA-KS), merging
      demographic, vital signs, clinical, and laboratory information. METHODS: We
      utilized a large, single-center database of patients admitted to acute care units
      in a large tertiary care hospital. Patients diagnosed with KS were compared to
      groups of patients with acute abdominal/flank/groin pain, genitourinary diseases,
      and other conditions. We analyzed multiple information domains (several thousands
      of variables) using a collection of statistical and machine learning models with
      feature selectors. We compared sensitivity, specificity and area under the
      receiver operating characteristic (AUROC) of our approach with the STONE score,
      using cross-validation. RESULTS: Thirty eight thousand five hundred and ninety
      seven distinct adult patients were admitted to critical care between 2001 and
      2012, of which 217 were diagnosed with KS, and 7446 with acute pain (non-KS). The
      multi-domain approach using logistic regression yielded an AUROC of 0.86 and a
      sensitivity/specificity of 0.81/0.82 in cross-validation. Increase in performance
      was obtained by fitting a super-learner, at the price of lower interpretability.
      We discussed in detail comorbidity and lab marker variables independently
      associated with KS (e.g. blood chloride, candidiasis, sleep disorders).
      CONCLUSIONS: Although external validation is warranted, DACA-KS could be
      integrated into electronic health systems; the algorithm has the potential used
      as an effective tool to help nurses and healthcare personnel during triage or
      clinicians making a diagnosis, streamlining patients' management in acute care.

PMID- 30119628
TI  - Healthcare reimbursement costs of children with type 1 diabetes in the
      Netherlands, a observational nationwide study (Young Dudes-4).
AB  - BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most common chronic
      diseases in children. Studies on costs related to T1DM are scarce and focused
      primarily on the costs directly related to diabetes. We aimed to investigate both
      the overall healthcare costs and the more specific costs related to the
      management of diabetes. METHODS: This is a retrospective and observational,
      nationwide cohort study of all Dutch children (aged 0-18 years) with T1DM. Data
      were collected from the national registry for healthcare reimbursement, in which
      all Dutch insurance companies combine their reimbursement data. In the
      Netherlands for all Dutch citizens health care is covered by law and all children
      are treated by hospital-based paediatricians. RESULTS: We analysed 6710 children
      distributed over 81 hospitals: 475 children in 6 university hospitals and 6235
      children in 75 general hospitals. Total reimbursement for all children with T1DM
      over the period 2009 to 2011 was ? 167,494,732 corresponding to an annual mean of
      ? 55,831,577 of total costs and ? 8326 euros per child. When comparing small
      (between 26 and 54 patients), medium (57-84 patients) and large (88-248 patients)
      general hospitals, costs per patient were highest in the hospitals with the
      highest number of T1DM patients. The costs for devices, secondary care and
      pharmaceutics had most impact on total expenditures. Over the study period, there
      was a slight decrease in per person costs. CONCLUSION: The overall health
      expenditure of a child with T1DM is more than ? 8000 per patient per annum. Given
      the move towards more device-intensive multidisciplinary care for these patients,
      the costs of treating T1DM in children are likely to increase further in the
      coming years.

PMID- 30119629
TI  - Reuse of cardiac organs in transplantation: an ethical analysis.
AB  - BACKGROUND: This paper examines the ethical aspects of organ transplant surgery
      in which a donor heart is transplanted from a first recipient, following
      determination of death by neurologic criteria, to a second recipient.
      Retransplantation in this sense differs from that in which one recipient
      undergoes repeat heart transplantation of a newly donated organ, and is thus
      referred to here as "reuse cardiac organ transplantation." METHODS: Medical,
      legal, and ethical analysis, with a main focus on ethical analysis. RESULTS: From
      the medical perspective, it is critical to ensure the quality and safety of
      reused organs, but we lack sufficient empirical data pertaining to medical risk.
      From the legal perspective, a comparative examination of laws in the United
      States and Japan affirms no illegality, but legal scholars disagree on the
      appropriate analysis of the issues, including whether or not property rights
      apply to transplanted organs. Ethical arguments supporting the reuse of organs
      include the analogous nature of donation to gifts, the value of donations as
      inheritance property, and the public property theory as it pertains to organs.
      Meanwhile, ethical arguments such as those that address organ recycling and
      identity issues challenge organ reuse. CONCLUSION: We conclude that organ reuse
      is not only ethically permissible, but even ethically desirable. Furthermore, we
      suggest changes to be implemented in the informed consent process prior to organ
      transplantation. The organ transplant community worldwide should engage in wider
      and deeper discussions, in hopes that such efforts will lead to the timely
      preparation of guidelines to implement reuse cardiac organ transplantation as
      well as reuse transplantation of other organs such as kidney and liver.

PMID- 30119630
TI  - Modeling patient access to therapeutic oxytocin in Zanzibar, Tanzania.
AB  - BACKGROUND: Our objective is to estimate the effects of therapeutic oxytocin
      supply chain factors and social determinants of health on patient access to
      oxytocin in low-income settings using system dynamics modeling. Postpartum
      hemorrhage (PPH), a major cause of maternal mortality disproportionately affects
      women in low and middle income countries (LMICs). The World Health Organization
      recommends therapeutic oxytocin as the frontline uterotonic for PPH management
      and prevention. However, lack of access to quality therapeutic oxytocin in
      Tanzania, and throughout Sub-Saharan Africa, continues to result in a high number
      of preventable maternal deaths. METHODS: We used publicly available data from
      Zanzibar and Sub-Saharan Africa, literature review, oxytocin degradation kinetics
      and previously developed systems dynamics models to understand the barriers in
      patient access to quality therapeutic oxytocin. RESULTS: The model makes four
      basic predictions. First, there is a major gap between therapeutic oxytocin
      procurement and availability. Second, it predicts that at current population
      increase rates, oxytocin supply will have to be doubled in the next 30 years.
      Third, supply and storage temperature until 30  degrees C has minimal effect on
      oxytocin quality and finally distance of 5 km or less to birthing facility has a
      small effect on overall access to oxytocin. CONCLUSIONS: The model provides a
      systems level approach to therapeutic oxytocin access, incorporating supply and
      procurement, socio-economic factors, as well as storage conditions to understand
      how women's access to oxytocin over time can be sustained for better health
      outcomes.

PMID- 30119631
TI  - Effect of low-intensity pulsed ultrasound on distraction osteogenesis: a
      systematic review and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) is a common adjunct used to
      promote bone healing for fresh fractures and non-unions, but its efficacy for
      bone distraction osteogenesis remains uncertain. This study aims to determine
      whether LIPUS can effectively and safely reduce the associated treatment time for
      patients undergoing distraction osteogenesis. METHODS: MEDLINE, EMBASE, and the
      Cochrane Library were searched until May 1, 2018, without language restriction.
      Studies should be randomized controlled trials (RCTs) or quasi-RCTs of LIPUS
      compared with sham devices or no devices in patients who undergo distraction
      osteogenesis. The primary outcome was the treatment time. The secondary outcome
      was the risk of complications. Treatment effects were assessed using mean
      differences, standardized mean differences, or risk ratios using a random-effects
      model. The Cochrane risk-of-bias tool was used to assess the risk of bias. The I2
      statistic was used to assess the heterogeneity. The GRADE system was used to
      evaluate the evidence quality. RESULTS: A total of 7 trials with 172 patients
      were included. The pooled results suggested that during the process of
      distraction osteogenesis, LIPUS therapy did not show a statistically significant
      reduction in the treatment time (mean difference, - 8.75 days/cm; 95% CI, - 20.68
      to 3.18 days/cm; P = 0.15; I2 = 72%) or in the risk of complications (risk ratio,
      0.90 in favor of LIPUS; 95% CI, 0.65 to 1.24; I2 = 0%). Also, LIPUS therapy did
      not show a significant effect on the radiological gap fill area (standardized
      mean difference, 0.48 in favor of control; 95%CI, - 1.49 to 0.52; I2 = 0%), the
      histological gap fill length (standardized mean difference, 0.76 in favor of
      control; 95%CI, - 1.78 to 0.27; I2 = 0%), or the bone density increase
      (standardized mean difference, 0.43 in favor of LIPUS; 95%CI, - 0.02 to 0.88; I2
      = 0%). CONCLUSIONS: Among patients undergoing distraction osteogenesis, neither
      the treatment time nor the risk of complications could be reduced by LIPUS
      therapy. The currently available evidence is insufficient to support the routine
      use of this intervention in clinical practice. TRIAL REGISTRATION: CRD
      42017073596.

PMID- 30119632
TI  - Service user and carer involvement in mental health care safety: raising concerns
      and improving the safety of services.
AB  - BACKGROUND: Previous research into improving patient safety has emphasised the
      importance of responding to and learning from concerns raised by service users
      and carers. Expertise gained by the experiences of service users and their carers
      has also been seen as a potential resource to improve patient safety. We know
      little about the ease of raising concerns within mental health services, and the
      potential benefits of involving service users and carers in safety interventions.
      This study aimed to explore service user and carer perceptions of raising safety
      concerns, and service user, carer and health professional views on the potential
      for service user and carer involvement in safety interventions. METHODS: UK
      service users, carers and health professionals ( n= 185) were recruited via
      social media to a cross-sectional survey focussed on raising concerns about
      safety issues and views on potential service user and carer participation in
      safety interventions. Data were analysed using descriptive statistics, and free
      text responses were coded into categories. RESULTS: The sample of 185
      participants included 90 health professionals, 77 service users and 18 carers.
      Seventy seven percent of service users and carers reported finding it very
      difficult or difficult to raise concerns. Their most frequently cited barriers to
      raising concerns were: services did not listen; concerns about repercussions; and
      the process of raising concerns, especially while experiencing mental ill health.
      There was universal support from health professionals for service user and carer
      involvement in safety interventions and over half the service users and carers
      supported involvement, primarily due to their expertise from experience.
      CONCLUSIONS: Mental health service users and carers experience difficulties in
      raising safety concerns meaning that potentially useful information is being
      missed. All the health professionals and the majority of service users and carers
      saw potential for service users and carer involvement in interventions to improve
      safety, to ensure their experiences are taken into consideration. The results
      provide guidance for future research about the most effective ways of ensuring
      that concerns about safety can be both raised and responded to, and how service
      user and carer involvement in improving safety in mental health care can be
      further developed.

PMID- 30119634
TI  - The effects of hyperlipidemia on rotator cuff diseases: a systematic review.
AB  - BACKGROUND: Rotator cuff disease is a common condition that causes shoulder pain
      and functional disability. Recent studies suggested that hyperlipidemia might be
      associated with the development of rotator cuff disease. The objective of this
      study was to explore the relationship of hyperlipidemia and rotator cuff
      diseases. METHODS: A computerized search using relevant search terms was
      performed in the PubMed, EMBASE, and Cochrane Library databases, as well as a
      manual search of reference and citation lists of the included studies. Searches
      were limited to studies that explored the association of hyperlipidemia and
      rotator cuff diseases. RESULTS: Sixteen studies were included in this systematic
      review. Ten of sixteen included studies suggested an association between
      dyslipidemia and rotator cuff diseases, while the other six studies did not find
      an association. Two studies demonstrated there were an association between
      statins and reduced risk of developing rotator cuff diseases or decreased
      incidence of revision after rotator cuff repair. CONCLUSION: The current study
      suggested that there was an association between hyperlipidemia and rotator cuff
      diseases. Furthermore, current evidence suggested that use of statins could
      decrease the risk of developing rotator cuff diseases and the incidence of
      revision after rotator cuff repair. Future high-quality studies are highly needed
      to confirm these findings.

PMID- 30119633
TI  - Selective resistance profiles emerging in patient-derived clinical isolates with
      cabotegravir, bictegravir, dolutegravir, and elvitegravir.
AB  - BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended for
      first-line HIV therapy based on their relatively high genetic barrier to
      resistance. Although raltegravir (RAL) and elvitegravir (EVG) resistance profiles
      are well-characterized, resistance patterns for dolutegravir (DTG), bictegravir
      (BIC), and cabotegravir (CAB) remain largely unknown. Here, in vitro drug
      selections compared the development of resistance to DTG, BIC, CAB, EVG and RAL
      using clinical isolates from treatment-naive primary HIV infection (PHI) cohort
      participants (n = 12), and pNL4.3 recombinant strains encoding patient-derived
      Integrase with (n = 5) and without (n = 5) the E157Q substitution. RESULTS:
      Patient-derived viral isolates were serially passaged in PHA-stimulated cord
      blood mononuclear cells in the presence of escalating concentrations of INSTIs
      over the course of 36-46 weeks. Drug resistance arose more rapidly in primary
      clinical isolates with EVG (12/12), followed by CAB (8/12), DTG (8/12) and BIC
      (6/12). For pNL4.3 recombinant strains encoding patient-derived integrase, the
      comparative genetic barrier to resistance was RAL > EVG > CAB > DTG and BIC. The
      E157Q substitution in integrase delayed the advent of resistance to INSTIs. With
      EVG, T66I/A, E92G/V/Q, T97A or R263K (n = 16, 3, 2 and 1, respectively) arose by
      weeks 8-16, followed by 1-4 accessory mutations, conferring high-level resistance
      (> 100-fold) by week 36. With DTG and BIC, solitary R263K (n = 27), S153F/Y (n =
      7) H51Y (n = 2), Q146 R (n = 3) or S147G (n = 1) mutations conferred low-level (<
      3-fold) resistance at weeks 36-46. Similarly, most CAB selections (n = 18)
      resulted in R263K, S153Y, S147G, H51Y, or Q146L solitary mutations. However,
      three CAB selections resulted in Q148R/K followed by secondary mutations
      conferring high-level cross-resistance to all INSTIs. EVG-resistant viruses
      (T66I/R263K, T66I/E157Q/R263K, and S153A/R263K) retained residual susceptibility
      when switched to DTG, BIC or CAB, losing T66I by week 27. Two EVG-resistant
      variants developed resistance to DTG, BIC and CAB through the additional
      acquisition of E138A/Q148R and S230N, respectively. One EVG-resistant variant
      (T66I) acquired L74M/G140S/S147G, L74M/E138K/S147G and H51Y with DTG CAB and BIC,
      respectively. CONCLUSIONS: Second generation INSTIs show a higher genetic barrier
      to resistance than EVG and RAL. The potency of CAB was lower than BIC and DTG.
      The development of Q148R/K with CAB can result in high-level cross-resistance to
      all INSTIs.

PMID- 30119636
TI  - Use of menstrual cups among school girls: longitudinal observations nested in a
      randomised controlled feasibility study in rural western Kenya.
AB  - BACKGROUND: A menstrual cup can be a good solution for menstrual hygiene
      management in economically challenged settings. As part of a pilot study we
      assessed uptake and maintenance of cup use among young school girls in Kenya.
      METHODS: A total of 192 girls between 14 to 16 years were enrolled in 10 schools
      in Nyanza Province, Western Kenya; these schools were assigned menstrual cups as
      part of the cluster-randomized pilot study. Girls were provided with menstrual
      cups in addition to training and guidance on use, puberty education, and
      instructions for menstrual hygiene. During repeated individual visits with
      nurses, girls reported use of the menstrual cup and nurses recorded colour change
      of the cup. RESULTS: Girls were able to keep their cups in good condition, with
      only 12 cups (6.3%) lost (dropped in toilet, lost or destroyed). Verbally
      reported cup use increased from 84% in the first 3 months (n = 143) to 96% after
      9 months (n = 74). Colour change of the cup, as 'uptake' indicator of use, was
      detected in 70.8% of 192 participants, with a median time of 5 months (range 1-14
      months). Uptake differed by school and was significantly higher among girls who
      experienced menarche within the past year (adjusted risk ratio 1.29, 95% CI 1.04
      1.60), and was faster among girls enrolled in the second study year (hazard ratio
      3.93, 95% CI 2.09-7.38). The kappa score comparing self-report and cup colour
      observation was 0.044 (p = 0.028), indicating that agreement was only slightly
      higher than by random chance. CONCLUSIONS: Objective evidence through cup colour
      change suggests school girls in rural Africa can use menstrual cups, with uptake
      improving with peer group education and over time. TRIAL REGISTRATION:
      ISRCTN17486946 . Retrospectively registered 09 December 2014.

PMID- 30119635
TI  - IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE2.
AB  - BACKGROUND: Interleukin-33 (IL-33) participates in various types of diseases
      including cancers. Previous studies of this cytokine in cancers mainly focused on
      its regulation on immune responses by which IL-33 modulated cancer progression.
      The IL-33 triggered signals in cancer cells remain unclear. METHODS: We analyzed
      IL-33 gene expression in human colorectal cancer (CRC) tissues and carried out
      gene enrichment analysis with TCGA Data Portal. We studied CRC proliferation in
      vivo by inoculating MC38 tumors in IL-33 transgenic mice. We investigated the
      cell proliferation in vitro with primary CRC cells isolated from fresh human CRC
      tissues, human CRC cell line HT-29 and mouse CRC cell line MC38. To evaluate the
      proliferation modulating effects of recombinant IL-33 incubation and other
      administrated factors, we measured tumor growth, colony formation, cell
      viability, and the expression of Ki67 and proliferating cell nuclear antigen
      (PCNA). We used several inhibitors, prostaglandin E2 (PGE2) neutralizing
      antibody, ST2 blocking antibody and specific shRNA expressing plasmid to study
      the pathway mediating IL-33-induced CRC proliferation. The IL-33 receptor ST2 in
      human CRC tissues was detected by immunohistochemistry staining and western
      blotting. The ST2-positive or negative subsets of primary CRC cells were acquired
      by flow cytometry sorting. RESULTS: We found that IL-33 expression was correlated
      with the gene signature of cell proliferation in 394 human CRC samples. The MC38
      tumors grew more rapidly and the tumor Ki67 and PCNA were expressed at higher
      levels in IL-33 transgenic mice than in wild-type mice. IL-33 promoted cell
      growth, colony formation and expression of Ki67 and PCNA in primary CRC cells as
      well as CRC cell lines. IL-33 activated cycloxygenase-2 (COX2) expression and
      increased PGE2 production, whereas the COX2 selective inhibitor and PGE2
      neutralizing antibody abolished the proliferation promoting effect of IL-33. ST2
      blockade, ST2-negative sorting, NF-kappaB specific inhibitor and NF-kappaB
      specific shRNA (shP65) abrogated the COX2 induction caused by IL-33. CONCLUSION:
      IL-33 facilitates proliferation of colorectal cancer dependent on COX2/PGE2. IL
      33 functions via its receptor ST2 and upregulates COX2 expression through NF
      kappaB signaling. Understanding the IL-33 signal transduction in CRC cells
      provides potential therapeutic targets for clinical treatment.

PMID- 30119637
TI  - Proximal third humeral shaft fractures fixed with long helical PHILOS plates in
      elderly patients: benefit of pre-contouring plates on a 3D-printed model-a
      retrospective study.
AB  - BACKGROUND: To explore the clinical efficacy of 3D printing fracture models to
      assist in creating pre-contoured plates to treat proximal third humeral shaft
      fractures. METHODS: We retrospectively identified proximal third humeral shaft
      fractures treated between February 2012 and February 2015. The patients were
      divided into two groups according to the treatment procedure: a Synbone group and
      a 3D-printed group. In the Synbone group, long proximal humeral internal locking
      system plates were pre-contoured into helical shape on Synbones before surgery,
      while in the 3D-printed group, they were contoured on 3D-printed bone models. The
      pre-contoured plates were sterilized before surgery and were then used for
      fracture fixation during surgery. Duration of surgeries, blood loss volumes, the
      incidence of complications, and the time to fracture union were recorded, and
      functional outcomes were assessed by the Constant-Murley shoulder score and the
      Mayo Elbow Performance Score (MEPS) at 1-year follow-up. RESULTS: The subjects
      comprised 46 patients; 25 patients were allocated to the Synbone group and the
      remaining 21 to the 3D-printed group. There was no significant difference between
      the baseline characteristics of the two groups. At the 1-year follow-up visit,
      all fractures were healed and showed a satisfactory outcome. There were no
      instances of iatrogenic radial nerve injury, and there was no significant
      difference between the two groups with regard to fracture union time, Constant
      Murley score, or MEPS score. Surgery duration was significantly shorter in the 3D
      printed group compared to the Synbone group (42.62 vs. 60.36 min, P = 0.001), and
      the 3D-printed group lost less blood during surgery (105.19 vs. 120.80 ml, P =
      0.001). In addition, in the 3D-printed group, 9 surgeries were finished by senior
      attending doctors and 12 were finished by junior attending doctors; however,
      there was no significant difference between the 1-year outcomes of the two grades
      of surgeons. CONCLUSIONS: Our results show that the 3D printing technique is
      helpful in shortening the duration of surgery, reducing blood loss volume, and in
      making this surgical procedure easier for less-experienced surgeons. TRIAL
      REGISTRATION: This clinical study was registered in CHICTR on September 30, 2017
      (number 17012852 ).

PMID- 30119638
TI  - Theory and practice of social norms interventions: eight common pitfalls.
AB  - BACKGROUND: Recently, Global Health practitioners, scholars, and donors have
      expressed increased interest in "changing social norms" as a strategy to promote
      health and well-being in low and mid-income countries (LMIC). Despite this
      burgeoning interest, the ability of practitioners to use social norm theory to
      inform health interventions varies widely. MAIN BODY: Here, we identify eight
      pitfalls that practitioners must avoid as they plan to integrate a social norms
      perspective in their interventions, as well as eight learnings. These learnings
      are: 1) Social norms and attitudes are different; 2) Social norms and attitudes
      can coincide; 3) Protective norms can offer important resources for achieving
      effective social improvement in people's health-related practices; 4) Harmful
      practices are sustained by a matrix of factors that need to be understood in
      their interactions; 5) The prevalence of a norm is not necessarily a sign of its
      strength; 6) Social norms can exert both direct and indirect influence; 7)
      Publicising the prevalence of a harmful practice can make things worse; 8) People
      led social norm change is both the right and the smart thing to do. CONCLUSIONS:
      As the understanding of how norms evolve in LMIC advances, practitioners will
      develop greater understanding of what works to help people lead change in harmful
      norms within their contexts. Awareness of these pitfalls has helped several of
      them increase the effectiveness of their interventions addressing social norms in
      the field. We are confident that others will benefit from these reflections as
      well.

PMID- 30119639
TI  - MAP17 predicts sensitivity to platinum-based therapy, EGFR inhibitors and the
      proteasome inhibitor bortezomib in lung adenocarcinoma.
AB  - BACKGROUND: The high incidence and mortality of lung tumours is a major health
      problem. Therefore, the identification both of biomarkers predicting efficacy for
      therapies in use and of novel efficacious therapeutic agents is crucial to
      increase patient survival. MAP17 (PDZK1IP1) is a small membrane-bound protein
      whose upregulation is reported as a common feature in tumours from diverse
      histological origins. Furthermore, MAP17 is correlated with tumour progression.
      METHODS: We assessed the expression of MAP17 in preclinical models, including
      cell lines and patient-derived xenografts (PDXs), assessing its correlation with
      sensitivity to different standard-of-care drugs in lung adenocarcinoma, as well
      as novel drugs. At the clinical level, we subsequently correlated MAP17
      expression in human tumours with patient response to these therapies. RESULTS: We
      show that MAP17 expression is induced during lung tumourigenesis, particularly in
      lung adenocarcinomas, and provide in vitro and in vivo evidence that MAP17 levels
      predict sensitivity to therapies currently under clinical use in adenocarcinoma
      tumours, including cisplatin, carboplatin and EGFR inhibitors. In addition, we
      show that MAP17 expression predicts proteasome inhibitor efficacy in this context
      and that bortezomib, an FDA-approved drug, may be a novel therapeutic approach
      for MAP17-overexpressing lung adenocarcinomas. CONCLUSIONS: Our results indicate
      a potential prognostic role for MAP17 in lung tumours, with particular relevance
      in lung adenocarcinomas, and highlight the predictive pot0065ntial of this
      membrane-associated protein for platinum-based therapy and EGFR inhibitor
      efficacy. Furthermore, we propose bortezomib treatment as a novel and efficacious
      therapy for lung adenocarcinomas exhibiting high MAP17 expression.

PMID- 30119640
TI  - The long-term outcomes and health-related quality of life of patients following
      blunt thoracic injury: a narrative literature review.
AB  - BACKGROUND: Major Trauma remains a leading cause of mortality and morbidity
      worldwide. Blunt Thoracic Injury (BTI) accounts for > 15% of United Kingdom (UK)
      trauma admissions and is consistently associated with respiratory related
      complications that include pneumonia and respiratory failure. Despite this, it is
      unclear in current clinical practice how BTI impacts on the recovering trauma
      patients after discharge from hospital. This study aimed to investigate the state
      of knowledge on the impact of BTI on the long-term outcomes and health-related
      quality of life (HRQoL). METHODS: Data were sourced from Ovid MEDLINE, Ovid
      EMBASE, CINAHL and Science Direct using a pre-defined systematic search strategy.
      A subsequent hand search of key references was used to identify potentially
      missed studies. Abstracts were screened for eligibility and inclusion. Fifteen
      studies met the eligibility criteria and were critically appraised. Data were
      extracted, analysed and synthesised in categories and sub-categories following a
      narrative approach. RESULTS: Three major themes were identified from the 15
      studies included in this review: (i) physical impact of BTI, (ii) psychological
      impact of BTI and (iii) socio-economic impact of BTI. The bulk of the available
      data focused on the physical impact where further sub-themes included: (i)
      physical functioning, (ii) ongoing unresolved pain, (iii) reduced respiratory
      function, (iv) thoracic structural integrity. Although there was a substantial
      difference in the length and method of follow up, there remains a general trend
      towards physical symptoms improving over time, particularly over the first six
      months after injury. Despite this, where sequelae continued at six months it
      remained likely that these would also be present at two years after injury.
      CONCLUSION: The literature review demonstrated that BTI is associated with
      substantial sequelae that impacts on all aspects of daily functioning. Despite
      this there remains a paucity of data relating to long term outcomes in the BTI
      population, especially relating to psychological and socio-economic impact. There
      is also little consensus on the measures, tools and time-frames used to measure
      outcomes and HRQoL in this population. The full impact of BTI on this population
      needs further exploration.

PMID- 30119641
TI  - Large plasmidome of dairy Lactococcus lactis subsp. lactis biovar diacetylactis
      FM03P encodes technological functions and appears highly unstable.
AB  - BACKGROUND: Important industrial traits have been linked to plasmids in
      Lactococcus lactis. RESULTS: The dairy isolate L. lactis subsp. lactis biovar
      diacetylactis FM03P was sequenced revealing the biggest plasmidome of all
      completely sequenced and published L. lactis strains up till now. The 12 plasmids
      that were identified are: pLd1 (8277 bp), pLd2 (15,218 bp), pLd3 (4242 bp), pLd4
      (12,005 bp), pLd5 (7521 bp), pLd6 (3363 bp), pLd7 (30,274 bp), pLd8 (47,015 bp),
      pLd9 (15,313 bp), pLd10 (39,563 bp), pLd11 (9833 bp) and pLd12 (3321 bp).
      Structural analysis of the repB promoters and the RepB proteins showed that
      eleven of the plasmids replicate via the theta-type mechanism, while only plasmid
      pLd3 replicates via a rolling-circle replication mechanism. Plasmids pLd2, pLd7
      and pLd10 contain a highly similar operon involved in mobilisation of the
      plasmids. Examination of the twelve plasmids of L. lactis FM03P showed that 10 of
      the plasmids carry putative genes known to be important for growth and survival
      in the dairy environment. These genes encode technological functions such as
      lactose utilisation (lacR-lacABCDFEGX), citrate uptake (citQRP), peptide
      degradation (pepO and pepE) and oligopeptide uptake (oppDFBCA), uptake of
      magnesium and manganese (2 mntH, corA), exopolysaccharides production (eps
      operon), bacteriophage resistance (1 hsdM, 1 hsdR and 7 different hsdS genes of a
      type I restriction-modification system, an operon of three genes encoding a
      putative type II restriction-modification system and an abortive infection gene)
      and stress resistance (2 uspA, cspC and cadCA). Acquisition of these plasmids
      most likely facilitated the adaptation of the recipient strain to the dairy
      environment. Some plasmids were already lost during a single propagation step
      signifying their instability in the absence of a selective pressure. CONCLUSIONS:
      Lactococcus lactis FM03P carries 12 plasmids important for its adaptation to the
      dairy environment. Some of the plasmids were easily lost demonstrating that
      propagation outside the dairy environment should be minimised when studying dairy
      isolates of L. lactis.

PMID- 30119642
TI  - Manifestation of anaplasmosis as cerebral infarction: a case report.
AB  - BACKGROUND: Human granulocytic anaplasmosis is a tick-borne zoonotic disease
      caused by Anaplasma phagocytophilum, an obligate intracellular granulocytotropic
      bacterium. CASE PRESENTATION: A 70-year-old female patient was admitted with the
      clinical signs of fever and an altered state of consciousness 1 week after
      experiencing a tick bite while planting lawn grass. Magnetic resonance imaging,
      performed at the time of admission, indicated cerebral infarction in the left
      basal ganglia, whereas increasing immunofluorescence assay antibody titers for A.
      phagocytophilum were also documented. A. phagocytophilum was identified using
      groEL and ankA targeted polymerase chain reaction and sequencing. Because of
      severe thrombocytopenia, only doxycycline was administered, without any
      antiplatelet agents. Subsequently, the symptoms improved without any focal
      neurologic sequela. CONCLUSION: This is the first reported case of cerebral
      infarction occurrence in an anaplasmosis patient.

PMID- 30119643
TI  - Clinical impact of endocapillary proliferation according to the Oxford
      classification among adults with Henoch-Schonlein purpura nephritis: a
      multicenter retrospective cohort study.
AB  - BACKGROUND: Henoch-Schonlein purpura nephritis (HSPN) is a form of small vessel
      vasculitis associated with purpura and IgA deposition in the glomeruli. The
      International Study of Kidney Disease in Children (ISKDC) classification predicts
      renal prognosis in children with HSPN, but not in adults. Additionally, it is not
      well known whether the Oxford classification 2016 and/or the Japanese Histologic
      classification (JHC) are associated with renal outcome. Herein, we investigated
      the relationship between pathological characteristics and renal outcome among
      adult patients with HSPN. METHODS: A multicenter retrospective cohort study was
      conducted in adult patients with HSPN who underwent renal biopsy between 2004 and
      2014. Two nephrologists classified each patient according to the Oxford
      classification 2016, JHC, and the ISKDC classification. Renal outcome was defined
      by a 30% decline in the eGFR and/or end-stage kidney disease. RESULTS: We
      enrolled 74 adult patients with HSPN (mean age, 47.8 +/- 17.4 years; mean eGFR,
      76.4 +/- 25.8 ml/min/1.73 m2; median proteinuria, 1.40 [IQR: 0.70-2.38] g/day).
      During a mean follow-up period of 68.0 +/- 33.0 months, fourteen patients (18.9%)
      reached the renal outcome, and all 14 had received immunosuppressive therapy. The
      log-rank test revealed that event-free renal survival was significantly shorter
      in patients with endocapillary proliferation (E1) according to the Oxford
      classification than in those with E0 (p = 0.0072). However, the JHC, ISKDC
      classification and other Oxford lesions could not demonstrate a significant
      difference in event-free renal survival. In a multivariate Cox model adjusted for
      clinical and pathological factors, age (HR, 1.57; 95% CI, 1.12-2.21) and E lesion
      (HR, 6.71; 95% CI, 1.06-42.7) were independent risk factors for renal outcome.
      CONCLUSIONS: Endocapillary proliferation is significantly associated with renal
      outcome in adult patients with HSPN, including those receiving immunosuppressive
      therapy. Other Oxford classification lesions, JHC, and ISKDC classification were
      not associated with renal outcome.

PMID- 30119645
TI  - An improvement of carotid intima-media thickness and pulse wave velocity in renal
      transplant recipients.
AB  - BACKGROUND: Renal transplantation can significantly improve the quality of life
      of patients with end stage renal disease (ESRD) who would otherwise require
      dialysis. Renal transplant (RT) recipients have higher risks of cardiovascular
      disease compared with general population. The carotid intima-media thickness
      (CIMT) and pulse wave velocity (PWV) have been used as the important predicting
      factor of vascular arteriosclerosis. Therefore, this study was to investigate the
      improvement of carotid intima-media thickness and pulse wave velocity in renal
      transplant recipients. METHODS: Thirty-one patients with chronic kidney disease
      being treated with hemodialysis, 31 renal transplant recipients and 84 healthy
      control subjects were included to have the clinical evaluations and
      ultrasonography of bilateral carotid arteries. CIMT and PWV were independently
      measured by two ultrasonographers using the technique of ultrasonic
      radiofrequency tracking and correlated with arteriosclerosis risk factors. The
      progression of CIMT and PWV with age were analyzed by linear regression models,
      and the slopes of curves were compared using Z test. RESULTS: Compared with the
      patients on hemodialysis, the CIMT was significantly lower in renal transplant
      recipients and healthy control. The PWV were higher in hemodialysis patients and
      renal transplant recipients than that of the subjects in control group. The
      progression is CIMT positively corelated with age and cumulative duration in
      renal transplant recipients and hemodialysis patients. In both hemodialysis
      patients and renal transplant recipients, age and cumulative time on dialysis
      were all positively correlated with the increase of PWV as well. CONCLUSIONS:
      Carotid intima-media thickness and pulse wave velocity is the predicting factors
      of developing arteriosclerosis, which were improved in renal transplant
      recipients.

PMID- 30119647
TI  - Correction to: Incidence and severity of postoperative sore throat: a randomized
      comparison of Glidescope with Macintosh laryngoscope.
AB  - We are thankful to Dr. Deepak Gupta (Clinical Assistant Professor Anesthesiology,
      Wayne State University/Detroit Medical Center) for bringing to our attention a
      typographical error in our manuscript [1].

PMID- 30119644
TI  - Effects of perioperative goal-directed fluid therapy combined with the
      application of alpha-1 adrenergic agonists on postoperative outcomes: a
      systematic review and meta-analysis.
AB  - BACKGROUND: Past studies have demonstrated that goal-directed fluid therapy
      (GDFT) may be more marginal than previously believed. However, beneficial effects
      of alpha-1 adrenergic agonists combined with appropriate fluid administration is
      getting more and more attention. This study aimed to systematically review the
      effects of goal-directed fluid therapy (GDFT) combined with the application of
      alpha-1 adrenergic agonists on postoperative outcomes following noncardiac
      surgery. METHODS: This meta-analysis included randomized controlled trials (RCTs)
      on GDFT combined with the application of alpha-1 adrenergic agonists in patients
      undergoing noncardiac surgery. The primary outcomes included the postoperative
      mortality rate and length of hospital stay (LOS). The secondary outcome indexes
      were the incidence of postoperative complications and recovery of postoperative
      gastrointestinal (GI) function. The traditional pairwise meta-analysis was
      conducted to compare the effect of fluid therapy. The quality of included RCTs
      was evaluated according to the Cochrane Collaboration's risk-of-bias tool. Also,
      the publication bias was detected using funnel plots, Egger's regression test,
      and Begg's adjusted rank correlation test. The meta-analysis was conducted using
      the RevMan 5.3 and Stata 14.0 software. RESULTS: Thirty-two eligible RCTs were
      included in this meta-analysis. Perioperative GDFT combined with the application
      of alpha-1 adrenergic agonists was associated with a significant reduction in LOS
      (P = 0.002; I2 = 69%), and overall complication rates (P = 0.04; I2 = 41%). It
      facilitated gastrointestinal function recovery, as demonstrated by shortening the
      time to first flatus by 6.30 h (P < 0.00001; I2 = 91%) and the time to toleration
      of solid food by 1.69 days (P < 0.00001; I2 = 0%). Additionally, there was no
      significant reduction in short-term mortality in the GDFT combined with alpha-1
      adrenergic agonists group (P = 0.05; I2 = 0%). CONCLUSION: This systematic review
      of available evidence suggested that the use of perioperative GDFT combined with
      alpha-1 adrenergic agonists might facilitate recovery in patients undergoing
      noncardiac surgery.

PMID- 30119646
TI  - Gold nanoparticles attenuates bacterial sepsis in cecal ligation and puncture
      mouse model through the induction of M2 macrophage polarization.
AB  - BACKGROUND: Gold nanoparticles (AuNP) have several biochemical advantageous
      properties especially for a candidate of drug carrier. However, the non
      conjugated AuNP has a higher rate of cellular uptake than the conjugated ones.
      Spherical AuNP in a proper size (20-30 nm) is non-toxic to mice and shows anti
      inflammatory properties. We tested if the administration of AuNP, as an adjuvant
      to antibiotics, could attenuate bacterial sepsis in cecal ligation and puncture
      (CLP) mouse model with antibiotic (imipenem/cilastatin). RESULTS: Indeed, AuNP
      administration at the time of CLP improved the survival, blood bacterial burdens,
      kidney function, liver injury and inflammatory cytokines (TNF-alpha, IL-6, IL
      1beta and IL-10). AuNP also decreased M1 macrophages (CD86 + ve in F4/80 + ve
      cells) and increased M2 macrophages (CD206 + ve in F4/80 + ve cells) in the
      spleens of sepsis mice. The weak antibiotic effect of AuNP was demonstrated as
      the reduction of E. coli colony after 4 h incubation. In addition, AuNP altered
      cytokine production of bone-marrow-derived macrophages including reduced TNF
      alpha, IL-6 and IL-1beta but increased IL-10 at 6 and 24 h. Moreover, AuNP
      induced macrophage polarization toward anti-inflammatory responses (M2) as
      presented by increased Arg1 (Arginase 1) and PPARgamma with decreased Nos2
      (inducible nitric oxide synthase, iNos) and Nur77 at 3 h after incubation in
      vitro. CONCLUSIONS: The adjuvant therapy of AuNP, with a proper antibiotic,
      attenuated CLP-induced bacterial sepsis in mice, at least in part, through the
      antibiotic effect and the induction of macrophage function toward the anti
      inflammatory responses.

PMID- 30119648
TI  - Identification of Yersinia enterocolitica isolates from humans, pigs and wild
      boars by MALDI TOF MS.
AB  - BACKGROUND: Yersinia enterocolitica is widespread within the humans, pigs and
      wild boars. The low isolation rate of Y. enterocolitica from food or
      environmental and clinical samples may be caused by limited sensitivity of
      culture methods. The main goal of present study was identification of presumptive
      Y. enterocolitica isolates using MALDI TOF MS. The identification of isolates may
      be difficult due to variability of bacterial strains in terms of biochemical
      characteristics. This work emphasizes the necessity of use of multiple methods
      for zoonotic Y. enterocolitica identification. RESULTS: Identification of Y.
      enterocolitica isolates was based on MALDI TOF MS, and verified by VITEK(r) 2
      Compact and PCR. There were no discrepancies in identification of all human' and
      pig' isolates using MALDI TOF MS and VITEK(r) 2 Compact. However three isolates
      from wild boars were not decisively confirmed as Y. enterocolitica. MALDI TOF MS
      has identified the wild boar' isolates designated as 3dz, 4dz, 8dz as Y.
      enterocolitica with a high score of matching with the reference spectra of MALDI
      Biotyper. In turn, VITEK(r) 2 Compact identified 3dz and 8dz as Y. kristensenii,
      and isolate 4dz as Y. enterocolitica. The PCR for Y. enterocolitica 16S rDNA for
      these three isolates was negative, but the 16S rDNA sequence analysis identified
      these isolates as Y. kristensenii (3dz, 4dz) and Y. pekkanenii (8dz). The wild
      boar' isolates 3dz, 4dz and 8dz could not be classified using biotyping. The main
      bioserotype present within pigs and human faeces was 4/O:3. It has been shown
      that Y. enterocolitica 1B/O:8 can be isolated from human faeces using ITC/CIN
      culturing. CONCLUSION: The results of our study indicate wild boars as a
      reservoir of new and atypical strains of Yersinia, for which protein and
      biochemical profiles are not included in the MALDI Biotyper or VITEK(r) 2 Compact
      databases. Pigs in the south-west Poland are the reservoir for pathogenic Y.
      enterocolitica strains. Four biochemical features included in VITEK(r) 2 Compact
      known to be common with Wauters scheme were shown to produce incompatible
      results, thus VITEK(r) 2 Compact cannot be applied in biotyping of Y.
      enterocolitica.

PMID- 30119649
TI  - Phenotypic variability of Niemann-Pick disease type C including a case with
      clinically pure schizophrenia: a case report.
AB  - BACKGROUND: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder
      with severe prognosis. Disease-specific therapy is crucial to prevent disease
      progression; however, diagnosing NPC is quite difficult because of remarkably
      variable clinical presentations. The NPC Suspicion Index (NPC-SI) was developed
      to overcome this problem. Identifying preclinical cases is important for
      prevention and therapy. Here, we report three newly diagnosed NPC cases, one
      typical juvenile-onset case and the cases of two sisters with symptoms
      neurologically/psychiatrically indistinguishable from dystonia and schizophrenia,
      respectively. CASE PRESENTATION: In Case 1, a 25-year-old man presented with a 14
      year history of intellectual disability, clumsiness, spastic ataxia, dysphagia,
      and frequent falls. Neurological examination revealed vertical supranuclear gaze
      palsy and involuntary movements. Ultrasonography revealed mild splenomegaly, and
      filipin staining of skin fibroblasts was positive with a variant staining
      pattern. NPC1 gene analysis showed compound heterozygous mutations, including
      c.1421C > T (p.P474L), a known causative mutation, and c.3722 T > C (p.L1241S), a
      new mutation. In Case 2, a 28-year-old woman, the proband, who had marked
      splenomegaly in her childhood, survived well, contrary to the expected severe
      prognosis of infantile NPC. She had minor neuropsychiatric symptoms including
      auditory hallucinations, nocturnal urination, and sleep paralysis. At the age of
      28 years, she presented with a 1-year history of orofacial and oromandibular
      painful dystonia. The patient's 35-year-old sister (Case 3) was diagnosed with
      schizophrenia. In both cases, filipin staining of skin fibroblasts was positive
      with variant staining patterns, as well as elevated levels of urinary bile acids.
      NPC1 gene analysis showed compound heterozygous mutations including c.3011C > T
      (p.S1004 L), a known causative mutation, and c.160_161insG (p.D54GfsX4), a new
      mutation. Their mother, who was under therapy with modafinil for narcolepsy,
      shared the latter mutation. CONCLUSIONS: Marked clinical variability was observed
      in our three cases. NPC could masquerade as a pure neuropsychiatric disorder such
      as dystonia or schizophrenia. Abdominal ultrasonography, history evaluation, and
      neurological examination were quite important in the diagnostic process.

PMID- 30119651
TI  - The phenomena of balanced effect between alpha-globin gene and of beta-globin
      gene.
AB  - BACKGROUND: Thalassemias (TM) are the most common autosomal recessive disorders
      in Southeast Asian countries. Both alpha- and beta-thalassemia lead to a decrease
      or absence of globin chains. The most serious of the thalassemia syndromes is
      thalassemia major which is characterized by a transfusion dependent anemia and
      subsequent iron overload caused by repeated blood transfusions. It is preventive
      by genotyping the parents. A better understanding of the laboratory data will
      help provide an accurate diagnosis of thalassemia major, and prevention and
      controlling programs in routine laboratories. CASE PRESENTATION: The patient was
      a one-year-old boy born to non-consanguineous parents. He was referred to our
      outpatient clinic for hemolytic anemia after a cold. Hematological investigations
      revealed severe anemia (Hb57 g/dL). The red cells displayed microcytosis,
      hypochromia and misshapen erythrocytes (MCV48.8 fL, MCH15.7 pg). Capillary
      electrophoresis (CE) electropherogram revealed normal level of HbA2 (3.2%) and
      elevated HbF (35.1%). The patient was diagnosed with beta-TM, based on severe
      microcytosis, hypochromia, normal Hb A2 and high Hb F level but no Hb H inclusion
      at the first visit. Later our molecular analysis revealed compound heterozygosity
      for codons 41-42 (-TTCT) (HBB: c.126_129delCTTT, beta0) and IVS-II-654 (C > T)
      (HBB: c.316-197C > T, beta+) mutation and deletional Hb H (--SEA/-alpha3.7).
      Thus, a combination of Hb H disease and a compound heterozygosity of beta+/beta0
      thalassemia (beta+/beta0-thal) was finally diagnosed. CONCLUSIONS: Genotype
      phenotype analysis shows that heterozygous mutations in the beta-globin gene
      could affect not only hematological parameters, but also elevate HbA2 levels.
      These effects could be ameliorated by the coinheritance of Hb H disease, which
      may be explained by the phenomena of the alpha-globin gene and of the beta-globin
      gene balanced effect.

PMID- 30119650
TI  - Prevalence, intensity and factors associated with soil-transmitted helminths
      infections among preschool-age children in Hoima district, rural western Uganda.
AB  - BACKGROUND: Over 80% of morbidity due to soil-transmitted helminthiasis (STH)
      occurs in low-income countries. Children under 5 account for 20-30% of the burden
      in endemic areas. This study assessed the prevalence, intensity and factors
      associated with STH infections among preschool-age children (PSAC) in Hoima
      district, Uganda. The PSAC are particularly vulnerable because the chronicity of
      this condition usually affects their physical and mental growth and development.
      METHODS: A cross-sectional study was carried out among 562 PSAC (1-5 years old)
      in 6 counties of Hoima district using Expanded Program on Immunization (EPI)
      method. Stool samples from children were examined using the formol ether
      concentration technique for STH egg detection. Egg counts were represented as egg
      per gram (EPG). A structured questionnaire was used to collect information on
      factors associated with STH infection. Generalized linear models were used to
      analyze relationships between STH infection and associated factors. RESULTS:
      Overall STH prevalence was 26.5%. Hookworm infection was the most prevalent
      (18.5%), followed by A.lumbricoides (9.8%) and T.trichiura (0.5%). Prevalence of
      STH infection was significantly higher in children aged 5 years (Pearson chi
      square test, p = 0.009) than in children aged 1 year. The general geometric mean
      (GM) counts for Hookworm infection was (696.1 EPG; range (530.3-913.8)) with
      girls having a higher GM (789.8 EPG; range (120-13,200)) than boys. Eating
      uncooked or unwashed vegetables (adj. Prevalence Ratio (PR) = 1.9, 95% CI: 1.3
      2.7) and fruits (adj.PR = 1.8, 95% CI: 1.1-2.8), indiscriminate disposal of young
      children's faeces (adj.PR = 1.5, 95% CI: 1.1-2.0); not washing hands after
      defecation (adj.PR = 2.6, 95% CI: 1.9-3.6); and not deworming children regularly
      (adj.PR = 1.4, 95% CI: 1.1-1.8) were significantly associated with STH infection.
      CONCLUSION: The prevalence of Soil transmitted helminths infection among
      preschool-age children in Hoima district significantly increased with age. Poor
      hygiene, inadequate sanitation and irregular deworming were associated with STH
      infections among PSAC in the study area. Intense health education on the
      importance of hygienic practices, improved sanitation and regular deworming of
      PSAC should be integrated into prevention and control programs.

PMID- 30119653
TI  - The contrasting role of technology as both supportive and hindering in the
      everyday lives of people with mild cognitive deficits: a focus group study.
AB  - BACKGROUND: It is well known that people with mild cognitive deficits face
      challenges when performing complex everyday activities, and that the use of
      technology has become increasingly interwoven with everyday activities. However,
      less is known of how technology might be involved, either as a support or
      hindrance, in different areas of everyday life and of the environments where
      challenges appear. The aim of this study was to investigate the areas of concern
      where persons with cognitive deficits meet challenges in everyday life, in what
      environments these challenges appear and how technology might be involved as part
      of the challenge and/or the solution to the challenge. METHODS: Data were
      gathered through four focus group interviews with participants that live with
      cognitive deficits or cohabit with a person with cognitive deficits, plus health
      professionals and researchers in the field. Data were transcribed, coded and
      categorized, and finally synthesized to trace out the involvement of technology.
      RESULTS: Five areas of concern in everyday life were identified as offering
      challenges to persons with cognitive deficits: A) Managing personal finances, B)
      Getting around, C) Meeting family and friends, D) Engaging with culture and media
      and, E) Doing everyday chores. Findings showed that the involvement of technology
      in everyday activities was often contrastive. It could be hindering and evoke
      stress, or it could bring about feelings of control; that is, being a part of the
      solution. The involvement of technology was especially obvious in challenges
      linked to Managing personal finances, which is a crucial necessity in many
      everyday activities. In contrast, technology was least obviously involved in the
      area Socializing with family and friends. CONCLUSIONS: The findings imply that
      technology used for orientation and managing finances, often used outside home,
      would benefit from being further developed in order to be more supportive; i.e.
      accessible and usable. To make a positive change for many people, the ideas of
      inclusive design fit well for this purpose and would contribute to an age
      friendly society.

PMID- 30119654
TI  - Learning from the experience of maternity healthcare workers in Malawi: a
      qualitative study leading to ten low-cost recommendations to improve working
      lives and quality of care.
AB  - BACKGROUND: In Malawi there are too few maternity healthcare workers to enable
      delivery of high quality care to women. These staff are often overworked and have
      low job satisfaction. Skilled maternity healthcare workers are essential to
      improve outcomes for mothers and babies. This study focuses on understanding the
      working life experience of maternity staff at district hospitals in Malawi with
      the aim of developing relevant low-cost solutions to improve working life.
      METHODS: A qualitative study using semi-structured interviews was undertaken in
      three district hospitals around Malawi's Capital city. Thirty-one staff formed a
      convenience sample, purposively selected to cover each cadre. Interviews were
      recorded, transcribed and then analysed using Interpretative Phenomenological
      Analysis complemented by Template Analysis to elicit the experience of maternity
      staff. RESULTS: Staff describe a system where respect, praise and support is
      lacking. Many want to develop their skills, however, there are barriers to
      advancement. Despite this, staff are motivated; they are passionate, committed
      professionals who endeavor to treat patients well, despite having few resources.
      Their 'superdiverse' background and experience helps them build resilience and
      strive to provide 'total care'. CONCLUSIONS: Improving working lives can improve
      the care women receive. However, this requires appropriate health policy and
      investment of resources. There are some inter-relational aspects that can be
      improved with little cost, which form the ten recommendations of this paper.
      These improvements in working life center around individual staff (respecting
      each other, appreciating each other, being available when needed, performing
      systematic clinical assessments and communicating clearly), leadership
      (supportive supervision and leading by example) and the system (transparent
      training selection, training being need driven, clinical skills being considered
      in rotation of staff). To improve working lives in this way will require
      commitment to change throughout the health system. Thus, it could help address
      preventable maternal and newborn deaths.

PMID- 30119652
TI  - Spatial heterogeneity and correlates of child malnutrition in districts of India.
AB  - BACKGROUND: Despite sustained economic growth and reduction in money metric
      poverty in last two decades, prevalence of malnutrition remained high in India.
      During 1992-2016, the prevalence of underweight among children had declined from
      53% to 36%, stunting had declined from 52% to 38% while that of wasting had
      increased from 17% to 21% in India. The national average in the level of
      malnutrition conceals large variation across districts of India. Using data from
      the recent round of National Family Health Survey (NFHS), 2015-16 this paper
      examined the spatial heterogeneity and meso-scale correlates of child
      malnutrition across 640 districts of India. METHODS: Moran's I statistics and
      bivariate LISA maps were used to understand spatial dependence and clustering of
      child malnutrition. Multiple regression, spatial lag and error models were used
      to examine the correlates of malnutrition. Poverty, body mass index (BMI) of
      mother, breastfeeding practices, full immunization, institutional births,
      improved sanitation and electrification in the household were used as meso scale
      correlates of malnutrition. RESULTS: The univariate Moran's I statistics was
      0.65, 0.51 and 0.74 for stunting, wasting and underweight respectively suggesting
      spatial heterogeneity of malnutrition in India. Bivariate Moran's I statistics of
      stunting with BMI of mother was 0.52, 0.46 with poverty and - 0.52 with
      sanitation. The pattern was similar with respect to wasting and underweight
      suggesting spatial clustering of malnutrition against the meso scale correlates
      in the geographical hotspots of India. Results of spatial error model suggested
      that the coefficient of BMI of mother and poverty of household were strong and
      significant predictors of stunting, wasting and underweight. The coefficient of
      BMI in spatial error model was largest found for underweight (beta = 0.38, 95%
      CI: 0.29-0.48) followed by stunting (beta = 0.23, 95% CI: 0.14-0.33) and wasting
      (beta = 0.11, 95% CI: 0.01-0.22). Women's educational attainment and
      breastfeeding practices were also found significant for stunting and underweight.
      CONCLUSION: Malnutrition across the districts of India is spatially clustered.
      Reduction of poverty, improving women's education and health, sanitation and
      child feeding knowledge can reduce the prevalence of malnutrition across India.
      Multisectoral and targeted intervention in the geographical hotspots of
      malnutrition can reduce malnutrition in India.

PMID- 30119655
TI  - Helicobacter pylori infection downregulates duodenal CFTR and SLC26A6 expressions
      through TGFbeta signaling pathway.
AB  - BACKGROUND: The pathogenesis of Helicobacter pylori (H. pylori) infection-induced
      duodenal ulcer remains to be elucidated. Duodenal mucosal bicarbonate secretion
      is the most important protective factor against acid-induced mucosal injury. We
      previously revealed that H. pylori infection downregulated the expression and
      functional activity of duodenal mucosal cystic fibrosis transmembrane conductance
      regulator (CFTR) and solute linked carrier 26 gene family A6 (SLC26A6) which are
      the two key duodenal mucosal epithelial cellular bicarbonate transporters to
      mediate duodenal bicarbonate secretion. In this study, we investigated the
      mechanism of H. pylori infection-induced duodenal CFTR and SLC26A6 expression
      downregulation. RESULTS: We found that H. pylori infection induced the increase
      of serum transforming growth factor beta (TGFbeta) level and duodenal mucosal
      TGFbeta expression and the decrease of duodenal mucosal CFTR and SLC26A6
      expressions in C57 BL/6 mice. The results from the experiments of human duodenal
      epithelial cells (SCBN) showed that H. pylori increased TGFbeta production and
      decreased CFTR and SLC26A6 expressions in SCBN cells. TGFbeta inhibitor SB431542
      reversed the H. pylori-induced CFTR and SLC26A6 expression decreases. The further
      results showed that TGFbeta directly decreased CFTR and SLC26A6 expressions in
      SCBN cells. TGFbeta induced the phosphorylation of p38 mitogen-activated protein
      kinase (MAPK) and P38 MAPK inhibitor SB203580 reversed the TGFbeta-induced CFTR
      and SLC26A6 expression decreases. CONCLUSIONS: H. pylori infection downregulates
      duodenal epithelial cellular CFTR and SLC26A6 expressions through TGFbeta
      mediated P38 MAPK signaling pathway, which contributes to further elucidating the
      pathogenesis of H. pylori-associated duodenal ulcer.

PMID- 30119656
TI  - 'You don't throw these things out:' an exploration of medicines retention and
      disposal practices in Australian homes.
AB  - BACKGROUND: Consumers most commonly discard unwanted medicines in household
      rubbish or drains, however, there are global concerns over the extent,
      environmental impact and health risks. When consumers procure or store medicines
      for future use, this can impact negatively on quality use of medicines and
      consumer safety. We sought greater insight into the extent of these practices by
      exploring the volume and types of medicines in Australian homes, and self
      reported practices related to medicine accumulation, use and disposal. This
      qualitative study formed part of a larger project that included a general
      population survey on household medicine disposal practices. METHODS: Semi
      structured telephone interviews were undertaken with a subset of respondents (n =
      166) from the survey. Participants were eligible if they were experienced
      medicine users, i.e. used five or more prescribed, over the counter, and/or
      complementary and alternative medicines. Participants were asked to collect and
      name all medicines in their household; further detail was obtained about
      medicines used only when required or no longer used, such as expiry dates and
      quantity remaining. The quantitative data on the number and type of medicines
      stored at home were analysed descriptively. All interviews were transcribed
      verbatim and thematically analysed. RESULTS: A total of 2301 medicines were
      identified as 1424 medicines not in everyday use (unused, unwanted, expired or
      when required) in 166 households, and 877 regularly used medicines by 119
      participants. Medicines were often stored in multiple locations, particularly
      kitchens. Although accidental ingestion in children and pets and decreased
      efficacy were recognised health risks, this did not always translate to
      appropriate storage, usage or disposal practices. Individual risk-benefit
      assessments were applied to decisions to retain, use or dispose of medicines,
      including expired medicines. CONCLUSIONS: Inappropriate medicine storage, use,
      and/or disposal practices raises public health concerns, particularly as there is
      a free returned medicines scheme available, and that this particular participant
      group were considered experienced medicine users. Healthcare professionals must
      act to address consumer misconceptions around the quality use of medicines,
      including medicine retention, storage and disposal. Future research is warranted
      to explore consumer practices in this context and confirm these findings in a
      younger, or healthier population.

PMID- 30119658
TI  - The NOD1 and NOD2 in mandarinfish (Siniperca chuatsi): molecular
      characterization, tissue distribution, and expression analysis.
AB  - BACKGROUND: NOD-like receptors (NLRs) are a family of cytoplasmic pattern
      recognition receptors (PRRs), of which NOD1 and NOD2, are the main representative
      members. Many investigations have focused on the role of NOD1 and NOD2 in the
      innate immune response in Cypriniformes and Siluriformes. As an important
      economic fish in Perciformes, little is known about the function of NOD1 and NOD2
      in mandarinfish (Siniperca chuatsi). RESULTS: The full-length NOD1 and NOD2 cDNA
      sequence was obtained using reverse transcription polymerase chain reaction (RT
      PCR) and rapid amplification of cDNA ends (RACE). The mandarinfish NOD1 and NOD2
      cDNA sequences contain 3247 bp and 3257 bp, and encode 918 amino acids and 988
      amino acids, respectively. Multiple sequence alignments showed that mNOD1 and
      mNOD2 share high similarity with that from other vertebrates. RT-PCR analysis
      revealed that relatively high levels of mNOD1 and mNOD2 mRNA were detected in
      gill and head kidney tissues, compared with the heart, spleen, liver, muscle, and
      intestine. In addition, the relative levels of mNOD1 and mNOD2 transcripts were
      significantly upregulated in three tissues when the fishes were challenged with
      LPS and Poly I:C, interestingly, the NOD1 mRNA got peaked earlier than NOD2 after
      LPS induction in the spleen, gill, and head kidney, and during Poly I:C
      treatment, the NOD2 mRNA got peaked at 8 h in spleen and gill, while NOD1 showed
      significant higher expression at 24 h post infection, besides, in head kidney,
      the NOD2 mRNA showed a great increasing trend and NOD1 got peaked at 16 h.
      Therefore the mNOD1 and mNOD2 may act differently within different tissues in
      different time during antiviral and antibacterial defense. CONCLUSIONS: These
      results revealed the dynamic mNOD1 and mNOD2 expression during viral and
      bacterial infections, which suggested the NOD1 and NOD2 play important roles in
      innate immune of mandarinfish.

PMID- 30119657
TI  - Examining the relationships between walkability and physical activity among older
      persons: what about stairs?
AB  - BACKGROUND: Walkability is considered an important dimension of healthy
      communities. However, variable associations between measures of walkability and
      physical activity have been observed, particularly among older persons. Given the
      challenges older persons may have navigating stairs on walking routes, the
      presence of stairs may be an explanatory factor for these mixed associations. The
      purposes of this scoping review were to determine whether studies examining the
      relationship between walkability and physical activity included items that
      assessed stairs and what relationships were found. METHODS: Systematic reviews
      were identified by entering search terms into five database search engines.
      Eligibility criteria were: a) published between 2008 and 2017, b) examined the
      relationship between walkability and physical activity, c) included a focus on
      persons aged 65 years and older, and d) written in English. The full articles for
      all primary studies included in eligible systematic reviews were then retrieved.
      Duplicates were removed. Information about where the study took place,
      walkability measures used, types of walkability data obtained (objective and/or
      subjective) and questions asked about stairs were extracted from the full text
      articles. RESULTS: Eleven systematic reviews were identified; seven were
      eligible. After removing duplicates, 289 primary studies remained for review.
      Measures of neighborhood walkability were present in 205 studies; a minority (n =
      5, 2.4%) included items about stairs. No information was obtained on the
      structural features of the stairs. CONCLUSIONS: The presence of stairs may deter
      older persons (and others) from walking outdoors. Standard measures to document
      the presence and characteristics of stairs, and sampling approaches to select
      stairs for assessment are needed. The inclusion of these measures would augment
      the utility and comparability of studies examining relationships between
      walkability and physical activity and better inform planning and policy
      decisions.

PMID- 30119659
TI  - Gastric leiomyosarcoma and diagnostic pitfalls: a case report.
AB  - BACKGROUND: Since the advent of immunohistochemistry for the diagnosis of stromal
      tumours, the incidence of leiomyosarcomas has significantly decreased. Nowadays,
      gastric leiomyosarcoma is an exceptionally rare tumour. We report the second case
      in the English literature of gastric leiomyosarcoma revealed with massive
      bleeding and hemodynamic instability and diagnostic pitfalls that we encountered.
      CASE PRESENTATION: A 63-year-old woman, with 2 years' history of dizziness and
      weakness probably related to an anaemic syndrome, presented to the emergency room
      with hematemesis, melena and hemodynamic instability. On examination, she had
      conjunctival pallor with reduced general condition, blood pressure of 90/45 mmHg
      and a pulse between 110 and 120 beats per minute. On digital rectal examination,
      she had melena. Laboratory blood tests revealed a haemoglobin level at 38 g/L.
      The patient was admitted to the intensive care department. After initial
      resuscitation, transfusion and intravenous Omeprazole continuous infusion, her
      condition was stabilized. She underwent upper gastrointestinal endoscopy showing
      a tumour of the cardia, protruding in the lumen with mucosal ulceration and clots
      in the stomach. Biopsies were taken. Histological examination showed interlacing
      bundles of spindle cells, ill-defined cell borders, elongated hyperchromatic
      nuclei with marked pleomorphism and paranuclear vacuolization.
      Immunohistochemistry showed positivity for Vimentine, a strong and diffuse
      immunoreactivity for smooth muscle actin (SMA). Immunoreactivities for KIT and
      DOG1 were doubtful. Computed tomography scan revealed a seven-cm tumour of the
      cardia, without adenopathy or liver metastasis. The patient underwent laparotomy.
      A total gastrectomy was performed without lymphadenectomy. Post-operative course
      was uneventful. Histological examination of the tumour specimen found the same
      features as preoperative biopsies with negative margins. We solicited a second
      opinion of an expert in a reference centre for sarcomas in France, who confirmed
      the diagnosis of a high grade gastric leiomyosarcoma. CONCLUSION: Gastric
      leiomyosarcoma is a rare tumour. Diagnosis is based on histological examination
      with immunohistochemistry, which could be sometimes confusing like in our case.
      The validation of a pathological expert is recommended.

PMID- 30119660
TI  - The Preterm Clinical Network (PCN) Database: a web-based systematic method of
      collecting data on the care of women at risk of preterm birth.
AB  - BACKGROUND: Despite much research effort, there is a paucity of conclusive
      evidence in the field of preterm birth prediction and prevention. The methods of
      monitoring and prevention strategies offered to women at risk vary considerably
      around the UK and depend on local maternity care provision. It is becoming
      increasingly recognised that this experience and knowledge, if captured on a
      larger scale, could be a utilized as a valuable source of evidence for others.
      The UK Preterm Clinical Network (UKPCN) was established with the aim of improving
      care and outcomes for women at risk of preterm birth through the sharing of a
      wealth of experience and knowledge, as well as the building of clinical and
      research collaboration. The design and development of a bespoke internet-based
      database was fundamental to achieving this aim. METHOD: Following consultation
      with UKPCN members and agreement on a minimal dataset, the Preterm Clinical
      Network (PCN) Database was constructed to collect data from women at risk of
      preterm birth and their children. Information Governance and research ethics
      committee approval was given for the storage of historical as well as
      prospectively collected data. Collaborating centres have instant access to their
      own records, while use of pooled data is governed by the PCN Database Access
      Committee. Applications are welcomed from UKPCN members and other established
      research groups. The results of investigations using the data are expected to
      provide insights into the effectiveness of current surveillance practices and
      preterm birth interventions on a national and international scale, as well as the
      generation of ideas for innovation and research. To date, 31 sites are registered
      as Data Collection Centres, four of which are outside the UK. CONCLUSION: This
      paper outlines the aims of the PCN Database along with the development process
      undertaken from the initial idea to live launch.

PMID- 30119661
TI  - Objectively measured physical activity in population-representative parent-child
      pairs: parental modelling matters and is context-specific.
AB  - BACKGROUND: Evidence for the context-specific influence of parental modelling on
      physical activity (PA) in childhood remains inconclusive. This nationwide Swiss
      study assessed the cross-sectional association between objectively measured PA of
      parents and their children and whether it varied across different levels of
      sociodemographic and environmental factors. In a second step a structural
      equation-model (SEM) was used to assess, whether associations between children's
      PA and sociodemographic and environmental factors are mediated by the parental PA
      behaviour. METHODS: The population-based sample of the SOPHYA-study consisted of
      889 children aged 6 to 16 years living in Switzerland and 1059 parents. PA was
      measured using accelerometers. Information on sociodemographics, sports
      behaviour, family characteristics, and perceived environment was obtained by
      telephone interview and parental questionnaire. Objective environmental data was
      allocated to each family's residential address using GIS (geographic information
      system). A structural equation model tested these factors for both independent
      associations with children's PA and associations mediated through the parental PA
      behaviour. RESULTS: Parental moderate to vigorous physical activity (MVPA) was
      associated with MVPA of their children in general (p < 0.001). Correlations
      between parents' and children's MVPA were stronger for children aged 10-12 years
      and for those living in the Italian speaking part of Switzerland. An increase of
      1 min of mother's and of father's MVPA was associated with 0.24 and 0.21 min more
      MVPA in children, respectively. Father's PA was associated with that of their
      sons, but not with that of their daughters, whereas the association of mothers'
      and children's PA did not depend on the parent-offspring sex-match. The pathway
      analysis in our structural equation model showed direct effects on children's
      MVPA as well as indirect effects mediated by the parental PA behaviour.
      CONCLUSIONS: Parental modelling seems relevant for children's PA, but not to the
      same degree in all children. Interventions focusing on strengthening parental PA
      behaviour for the promotion of PA in the young must consider additional
      contextual factors related to the socio-cultural and structural environment.

PMID- 30119663
TI  - A multi-center, double blind randomized controlled trial evaluating flap fixation
      after mastectomy using sutures or tissue glue versus conventional closure:
      protocol for the Seroma reduction After Mastectomy (SAM) trial.
AB  - BACKGROUND: Seroma formation is a common complication after mastectomy and is
      associated with delayed wound healing, infection, skin flap necrosis, patient
      discomfort and repeated visits to the out patient clinic to deal with seroma and
      its sequelae. Closing the dead space after mastectomy seems to be key in reducing
      seroma and its complications. Various methods have been described to reduce the
      dead space after mastectomy: closed suction drainage, quilting of the skin flaps
      and application of adhesive tissue glues. The aim of this trial is to compare
      seroma formation and its sequelae in the various methods of flap fixation.
      METHODS: This is a multicenter, double-blind, randomized controlled trial in
      female breast cancer patients undergoing mastectomy, with or without axillary
      clearance. Exclusion criteria consist of breast conserving therapy, direct breast
      reconstruction and incapacity to comprehend implications and extent of study and
      unable to sign for informed consent. A total of 336 patients will be randomized.
      Patients will be randomly allocated to one of three treatment arms consisting of
      flap fixation using ARTISS tissue glue with a low suction drain, flap fixation
      using sutures and a low suction drain or conventional wound closure (without flap
      fixation) and low suction drainage. Follow up will be conducted up to twelve
      months post surgery. The primary outcome is the number of seroma aspirations and
      secondary outcomes consist of number of out patient clinic visits, surgical skin
      infection rate, shoulder function, cosmesis, health-related quality of life and
      costs and cost-effectiveness (cost/QALY). DISCUSSION: This is the first study of
      its kind to evaluate the effect of flap fixation and its sequelae (ie seroma
      aspirations, number of out patient clinic visits, infection, shoulder function,
      patient assessed cosmesis, quality of life and cost-effectiveness) in a double
      blind randomized controlled trial. TRIAL REGISTRATION: This trial was approved by
      the hospitals' joint medical ethical committee (14-T-21, 2 June 2014). The SAM
      Trial is registered in ClinicalTrials.gov since October 2017, Identifier:
      NCT03305757 .

PMID- 30119662
TI  - Tracing the path of cancer initiation: the AA protein-based model for cancer
      genesis.
AB  - BACKGROUND: Cancer is a defiant disease which cure is still far from being
      attained besides the colossal efforts and financial means deployed towards that
      end. The continuing setbacks encountered with today's arsenal of anti-cancer
      drugs and cancer therapy modalities; show the need for a radical approach in
      order to get to the root of the problem. And getting to the root of cancer
      initiation and development leads us to challenge the present dogmas surrounding
      the pathogenesis of this disease. RESULTS: This comprehensive analysis brings to
      light the following points: (i) Cancer with its plethora of genetic and cellular
      symptoms could originate from one major event switching a cell from normalcy-to
      malignancy; (ii) The switching event is postulated to involve a pathological
      breakup of a non-mutated protein, called here AA protein, resulting in the
      acquisition of new cellular functions present only in cancer cells; (iii)
      Following this event, DNA mutations begin to accumulate as secondary events to
      ensure perpetuity of cancer. Supporting arguments for this protein-based model
      come mainly from these observations: (i) The AA protein-based model reconciles
      together the clonal-and-stem cell theories into one inclusive model; (ii) The
      breakup of a normal protein could be behind the cancer-linked inflammation
      symptom; (iii) Cancer hallmarks are but adaptive traits, earned as a result of
      the switch from normalcy-to-malignancy. CONCLUSIONS: Adaptation of cancer cells
      to their microenvironment and to different anti-cancer drugs is deemed here as
      the ultimate cancer hallmark, that needs to be understood and controlled. This
      adaptive power of cancer cells parallels that of bacteria also known with their
      resistance to a large range of substances in nature and in the laboratory.
      Consequently, cancer development could be viewed as a backward walk on the line
      of Evolution. Finally this unprecedented analysis demystifies cancer and puts the
      finger on the core problem of malignancy while offering ideas for its control
      with the ultimate goal of leading to its cure.

PMID- 30119665
TI  - Market-orienting reforms in rural health care in Sweden: how can equity in access
      be preserved?
AB  - BACKGROUND: Health care provision in rural and urban areas faces different
      challenges. In Sweden, health care provision has been predominantly public and
      equitable access to care has been pursued mainly through public planning and
      coordination. This is to ensure that health needs are met in the same manner in
      all parts of the country, including rural or less affluent areas. However, a
      marketization of the health care system has taken place during recent decades and
      the publicly planned system has been partially replaced by a new market logic,
      where private providers guided by financial concerns can decide independently
      where to establish their practices. In this paper, we explore the effects of
      marketization policies on rural health care provision by asking how policy makers
      in rural counties have managed to combine two seemingly contradictory health
      policy goals: to create conditions for market competition among health care
      providers and to ensure equal access to health care for all patients, including
      those living in rural and remote areas. METHODS: A qualitative case study within
      three counties in the northern part of Sweden, characterized by vast rural areas,
      was carried out. Legal documents, the "accreditation documents" regulating the
      health care quasi-markets in the three counties were analyzed. In addition,
      interviews with policy makers in the three county councils, representing the
      political majority, the opposition, and the political administration were
      conducted in April and May 2013. RESULTS: The findings demonstrate the
      difficulties involved in introducing market dynamics in health care provision in
      rural areas, as these reforms not only undermined existing resource allocation
      systems based on health needs but also undercut attempts by local policy makers
      to arrange for care provision in remote locations through planning and
      coordination. CONCLUSION: Provision of health care in rural areas is not well
      suited for market reforms introducing competition, as this may undermine the goal
      of equity in access to health care, even in a publicly financed health care
      system.

PMID- 30119666
TI  - Housing gaps, mosquitoes and public viewpoints: a mixed methods assessment of
      relationships between house characteristics, malaria vector biting risk and
      community perspectives in rural Tanzania.
AB  - BACKGROUND: House improvement and environmental management can significantly
      improve malaria transmission control in endemic communities. This study assessed
      the influence of physical characteristics of houses and surrounding environments
      on mosquito biting risk in rural Tanzanian villages, and examined knowledge and
      perceptions of residents on relationships between these factors and malaria
      transmission. The study further assessed whether people worried about these risks
      and how they coped. METHODS: Entomological surveys of indoor mosquito densities
      were conducted across four villages in Ulanga district, south-eastern Tanzania.
      The survey involved 48 sentinel houses sampled monthly and other sets of 48
      houses randomly recruited each month for one-off sampling over 12 months.
      Physical characteristics of the houses and surrounding environments were
      recorded. Questionnaire surveys were administered to 200 household heads to
      assess their knowledge and concerns regarding the observed housing and
      environmental features, and whether they considered these features when
      constructing houses. Focus group discussions, were conducted to clarify emergent
      themes on people's perceptions on relationships between housing or environmental
      factors and malaria transmission. RESULTS: The entomological surveys showed
      statistically higher indoor densities of the malaria vectors (Anopheles
      arabiensis and Anopheles funestus) in houses with mud walls compared to plastered
      or brick walls, open eaves compared to closed eaves and unscreened windows
      compared to screened windows. Most respondents reported that their houses allowed
      mosquito entry, at least partially. Participants were aware that house structure
      and environmental characteristics influenced indoor mosquito densities and
      consequently malaria transmission. They were concerned about living in poorly
      constructed houses with gaps on eaves, walls, windows and doors but were
      constrained by low income. CONCLUSION: In rural south-eastern Tanzania,
      significant proportions of people still live in houses with open eaves,
      unscreened windows and gaps on doors. Though they are fully aware of associated
      mosquito biting and pathogen transmission risks, they are constrained by low
      income levels. The study proposes that community-based house improvement
      initiatives combined with targeted subsidies could lower the financial barriers,
      improve access to essential construction materials or designs, and significantly
      accelerate malaria transmission control in these communities.

PMID- 30119664
TI  - Agent-based models of malaria transmission: a systematic review.
AB  - BACKGROUND: Much of the extensive research regarding transmission of malaria is
      underpinned by mathematical modelling. Compartmental models, which focus on
      interactions and transitions between population strata, have been a mainstay of
      such modelling for more than a century. However, modellers are increasingly
      adopting agent-based approaches, which model hosts, vectors and/or their
      interactions on an individual level. One reason for the increasing popularity of
      such models is their potential to provide enhanced realism by allowing system
      level behaviours to emerge as a consequence of accumulated individual-level
      interactions, as occurs in real populations. METHODS: A systematic review of 90
      articles published between 1998 and May 2018 was performed, characterizing agent
      based models (ABMs) relevant to malaria transmission. The review provides an
      overview of approaches used to date, determines the advantages of these
      approaches, and proposes ideas for progressing the field. RESULTS: The rationale
      for ABM use over other modelling approaches centres around three points: the need
      to accurately represent increased stochasticity in low-transmission settings; the
      benefits of high-resolution spatial simulations; and heterogeneities in drug and
      vaccine efficacies due to individual patient characteristics. The success of
      these approaches provides avenues for further exploration of agent-based
      techniques for modelling malaria transmission. Potential extensions include
      varying elimination strategies across spatial landscapes, extending the size of
      spatial models, incorporating human movement dynamics, and developing
      increasingly comprehensive parameter estimation and optimization techniques.
      CONCLUSION: Collectively, the literature covers an extensive array of topics,
      including the full spectrum of transmission and intervention regimes. Bringing
      these elements together under a common framework may enhance knowledge of, and
      guide policies towards, malaria elimination. However, because of the diversity of
      available models, endorsing a standardized approach to ABM implementation may not
      be possible. Instead it is recommended that model frameworks be contextually
      appropriate and sufficiently described. One key recommendation is to develop
      enhanced parameter estimation and optimization techniques. Extensions of current
      techniques will provide the robust results required to enhance current
      elimination efforts.

PMID- 30119667
TI  - Correction to: Regulation of diabetic cardiomyopathy by caloric restriction is
      mediated by intracellular signaling pathways involving 'SIRT1 and PGC-1alpha'.
AB  - Unfortunately, after publication of this article [1], it was noticed that Table 1
      contained errors introduced during the production process. In the WT + AT column,
      the FS value is 21 +/- 7 and the Body Weight value is 25 +/- 2. In the WT + AT +
      CR column, the FS value is 46 +/- 14 and the Body Weight value is 19 +/- 1. The
      original article has been updated to reflect this.

PMID- 30119669
TI  - The molecular characteristic analysis of PRRSV GSWW/2015 strain and its
      pathogenicity to pigs.
AB  - BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is a severe
      disease, causing great economic losses to the pig industry. The causative agent,
      porcine reproductive and respiratory syndrome virus (PRRSV) is highly variable.
      Since the emergence of highly pathogenic PRRSV (HP-PRRSV) in China in 2006, this
      virus strain has undergone extensive variation. To investigate the genetic
      variation and pathogenicity of currently isolated PRRSV GSWW/2015 strain, its
      whole genome was sequenced and analyzed for the specific variation in NSP2, GP3
      and GP5 regions. Pigs were challenged with the isolated virus to investigate its
      pathogenicity. METHODS: The PRRSV GSWW/2015 strain was isolated by seeding the
      viral material in Marc-145 cells. The virus specific cytopathic effect (CPE) was
      confirmed by indirect immunofluorescent assay (IFA) and PCR to detect the virus
      protein and RNA. Nine pairs of primers were designed to obtain the complete
      genome by PCR. All PCR fragments were cloned into T-vector for sequencing. The
      genetic variation of GSWW/2015 strain was analyzed by multiple sequence
      alignments. Nineteen PRRSV-free piglets were intranasally challenged with 108
      copies of GSWW virus, while seven piglets were housed together as contact
      infected control. Clinical signs were recorded daily after challenge. Blood
      samples were obtained every week and the viral titer was detected by quantitative
      real-time PCR (qRT-PCR). The PRRSV specific antibody was detected by LSI ELISA
      kit. RESULTS: The complete genome of PRRSV GSWW/2015 strain (GenBank accession
      number KX767091) was obtained. The whole genome of this strain shares 88.5 and
      60.6% identity with VR-2332 and LV respectively, indicating that it belongs to
      the North American type (NA-type). Sequence alignments revealed that GSWW/2015
      strain has a discontinuous deletion of 30 amino acids in NSP2, which is similar
      with HP-PRRSV. Some amino acids mutations can be observed in antigenic epitope
      regions of GP3 and GP5 compared with earlier strains of HP-PRRSV. Some piglets
      showed typical clinical signs of PRRSV after challenge. Only four pigs showed
      viremia within 3 days after challenge, most pigs showed peaked viremia after 21
      28 days including 7 contact-infected pigs. Two pigs were detected to be positive
      for antibody to PRRSV at 14 days post infection (DPI), and 11 pigs (11/26) show
      seroconversion for PRRSV at 49 DPI. Twelve piglets died of PRRSV infection within
      two months. CONCLUSIONS: The genome of PRRSV GSWW/2015 strain shows the features
      of HP-PRRSV with 30 discontinuous amino acids deletion in NSP2 and some new amino
      acid mutations in epitope regions of GP5 and GP3, which might alter the
      antigenicity of the virus. Furthermore, the virus showed high virulence to
      piglets as reported in HP-PRRSV, and induced long-lasting viremia and low level
      of antibody responses. This work further enriched our knowledge on PRRSV
      evolution and pathogenicity.

PMID- 30119670
TI  - Differential achievements in childhood immunization across geographical regions
      of Pakistan: analysis of wealth-related inequality.
AB  - BACKGROUND: Childhood immunization is one of the most cost-effective
      interventions for child health. Still, many children are not able to receive
      completed immunization status. Wealth - related inequality in immunization is
      considered a major reason for equitable coverage of immunization in Pakistan.
      Therefore, we examine wealth-related inequality in completed childhood
      immunization and to assess achievement indices across geographical regions in
      Pakistan. METHODS: The analysis was based on a nationally representative
      demographic and health survey (DHS) of Pakistan, conducted in 2012-13. We
      examined completed childhood (12-23 months) immunization in the various regions
      of the country and we used concentration, extended concentration and achievement
      indices to demonstrate inequality across geographical regions in Pakistan.
      RESULTS: Inequality in completed childhood immunization was seen in Pakistan with
      concentration index (CI) of 0.181 (95% CI: 0.164-0.209). Regions with high
      average of complete immunization showed lower inequality except for Sindh.
      Despite having better average immunization coverage in Kyber Pakhtunkhwa, the
      relative change of 128% in concentration index (CI) from C2 (standard CI) to C5
      (when poorer quantile received highest weights) shows this to be also the most
      inequitable regions. Four parameters of inequality aversion (v = 2, 3, 4 & 5)
      demonstrated that 'dis - achievement' in completed immunization is densely
      concentrated among the poorer regions. Balochistan, Sindh and Gilgit Baltistan
      exhibited broader inequality gaps (93.75%, 83.35%, and 54.93%, respectively) at
      higher aversion parameter. CONCLUSIONS: As hypothesized, achievement index
      uncovers 'penalized' immunization coverage amongst the poorest population. Thus
      any policy that stringently focuses on improving average immunization rate
      without any strategy to deal with inequality will only improve immunization rate
      within wealthier groups. Based on these results, it is advisable to public health
      policy makers to use both aspect of information: average and degree of inequality
      in immunization coverage.

PMID- 30119668
TI  - Assessment of effectiveness and safety of repeat administration of
      proinflammatory primed allogeneic mesenchymal stem cells in an equine model of
      chemically induced osteoarthritis.
AB  - BACKGROUND: This study aimed at assessing the effectiveness and safety of
      repeated administrations of allogeneic bone marrow-derived mesenchymal stem cells
      (BM-MSCs) primed with tumor necrosis factor (TNF)-alpha and interferon-gamma in
      an equine model of chemically-induced osteoarthritis. Arthritis was induced in
      both radio-carpal (RC)-joints by amphotericin-B in 18 ponies, divided into three
      groups depending on the treatment injected: MSC-naive (n = 7), MSC-primed (n = 7)
      and control (n = 4). The study consisted of two phases and used one RC-joint of
      each animal in each phase, with four months time-lapse, in order to assess two
      end-points. Clinical, synovial, radiological and ultrasonographic follow-up was
      performed. At six months, animals were euthanized and both carpi were assessed by
      magnetic resonance imaging (MRI), gross anatomy, histopathology, histochemistry
      and gene expression. RESULTS: Clinical and synovial inflammatory signs were
      quicker reduced in MSC-treated groups and repeated allogeneic administration did
      not produce adverse reactions, but MSC-primed group showed slight and transient
      local inflammation after second injection. Radiology and MRI did not show
      significant differences between treated and control groups, whereas
      ultrasonography suggested reduced synovial effusion in MSC-treated groups. Both
      MSC-treated groups showed enhanced cartilage gross appearance at two compared to
      six months (MSC-naive, p < 0.05). Cartilage histopathology did not reveal
      differences but histochemistry suggested delayed progression of proteoglycan loss
      in MSC-treated groups. Synovium histopathology indicated decreased inflammation
      (p < 0.01) in MSC-primed and MSC-naive at two and six months, respectively. At
      two months, cartilage from MSC-primed group significantly (p < 0.05) upregulated
      collagen type II (COL2A1) and transforming growth factor (TGF)-beta1 and
      downregulated cyclooxygenase-2 and interleukin (IL)-1beta. At six months, MSC
      treatments significantly downregulated TNFalpha (p < 0.05), plus MSC-primed
      upregulated (p < 0.05) COL2A1, aggrecan, cartilage oligomeric protein, tissue
      inhibitor of metalloproteinases-2 and TGF-beta1. In synovium, both MSC-treatments
      decreased (p < 0.01) matrix metalloproteinase-13 expression at two months and MSC
      primed also downregulated TNFalpha (p < 0.05) and IL-1beta (p < 0.01).
      CONCLUSIONS: Both MSC-treatments provided beneficial effects, mostly observed at
      short-term. Despite no huge differences between MSC-treatments, the findings
      suggested enhanced anti-inflammatory and regulatory potential of MSC-primed.
      While further research is needed to better understand these effects and clarify
      immunogenicity implications, these findings contribute to enlarge the knowledge
      about MSC therapeutics and how they could be influenced.

PMID- 30119672
TI  - Note on the use of different approaches to determine the pore sizes of tissue
      engineering scaffolds: what do we measure?
AB  - BACKGROUND: Collagen-based scaffolds provide a promising option for the treatment
      of bone defects. One of the key parameters of such scaffolds consists of
      porosity, including pore size. However, to date, no agreement has been found with
      respect to the methodology for pore size evaluation. Since the determination of
      the exact pore size value is not possible, the comparison of the various methods
      applied is complicated. Hence, this study focuses on the comparison of two widely
      used methods for the characterization of porosity-scanning electron microscopy
      (SEM) and micro-computed tomography (micro-CT). METHODS: 7 types of collagen
      based composite scaffold models were prepared by means of lyophilization and
      collagen cross-linking. Micro-CT analysis was performed in 3D and in 2D (pore
      size parameters were: major diameter, mean thickness, biggest inner circle
      diameter and area-equivalent circle diameter). Afterwards, pore sizes were
      analyzed in the same specimens by an image analysis of SEM microphotographs. The
      results were statistically evaluated. The comparison of the various approaches to
      the evaluation of pore size was based on coefficients of variance and the semi
      quantitative assessment of selected qualities (e.g. the potential for direct 3D
      analysis, whole specimen analysis, non-destructivity). RESULTS: The pore size
      values differed significantly with respect to the parameters applied. Median
      values of pore size values were ranging from 20 to 490 um. The SEM values were
      approximately 3 times higher than micro-CT 3D values for each specimen. The Mean
      thickness was the most advantageous micro-CT 2D approach. Coefficient of variance
      revealed no differences among pore size parameters (except major diameter). The
      semi-quantitative comparison approach presented pore size parameters in
      descending order with regard to the advantages thereof as follows: (1) micro-CT
      3D, (2) mean thickness and SEM, (3) biggest inner circle diameter, major diameter
      and area equivalent circle diameter. CONCLUSION: The results indicated that micro
      CT 3D evaluation provides the most beneficial overall approach. Micro-CT 2D
      analysis (mean thickness) is advantageous in terms of its time efficacy. SEM is
      still considered as gold standard for its widespread use and high resolution.
      However, exact comparison of pore size analysis in scaffold materials remains a
      challenge.

PMID- 30119671
TI  - Diversity pattern of Duffy binding protein sequence among Duffy-negatives and
      Duffy-positives in Sudan.
AB  - BACKGROUND: Vivax malaria is a leading public health concern worldwide. Due to
      the high prevalence of Duffy-negative blood group population, Plasmodium vivax in
      Africa historically is less attributable and remains a neglected disease. The
      interaction between Duffy binding protein and its cognate receptor, Duffy antigen
      receptor for chemokine plays a key role in the invasion of red blood cells and
      serves as a novel vaccine candidate against P. vivax. However, the polymorphic
      nature of P. vivax Duffy binding protein (DBP), particularly N-terminal cysteine
      rich region (PvDBPII), represents a major obstacle for the successful design of a
      DBP-based vaccine to enable global protection. In this study, the level of
      pvdbpII sequence variations, Duffy blood group genotypes, number of haplotypes
      circulating, and the natural selection at pvdbpII in Sudan isolates were analysed
      and the implication in terms of DBP-based vaccine design was discussed. METHODS:
      Forty-two P. vivax-infected blood samples were collected from patients from
      different areas of Sudan during 2014-2016. For Duffy blood group genotyping, the
      fragment that indicates GATA-1 transcription factor binding site of the FY gene (
      33T > C) was amplified by PCR and sequenced by direct sequencing. The region II
      flanking pvdbpII was PCR amplified and sequenced by direct sequencing. The
      genetic diversity and natural selection of pvdbpII were done using DnaSP ver 5.0
      and MEGA ver 5.0 programs. Based on predominant, non-synonymous, single
      nucleotide polymorphisms (SNPs), prevalence of Sudanese haplotypes was assessed
      in global isolates. RESULTS: Twenty SNPs (14 non-synonymous and 6 synonymous)
      were identified in pvdbpII among the 42 Sudan P. vivax isolates. Sequence
      analysis revealed that 11 different PvDBP haplotypes exist in Sudan P. vivax
      isolates and the region has evolved under positive selection. Among the
      identified PvDBP haplotypes five PvDBP haplotypes were shared among Duffy
      negative as well as Duffy-positive individuals. The high selective pressure was
      mainly found on the known B cell epitopes (H3) of pvdbpII. Comparison of Sudanese
      haplotypes, based on 10 predominant non-synonymous SNPs with 10 malaria-endemic
      countries, demonstrated that Sudanese haplotypes were prevalent in most endemic
      countries. CONCLUSION: This is the first pvdbp genetic diversity study from an
      African country. Sudanese isolates display high haplotype diversity and the gene
      is under selective pressure. Haplotype analysis indicated that Sudanese
      haplotypes are a representative sample of the global population. However, studies
      with a large number of samples are needed. These findings would be valuable for
      the development of PvDBP-based malaria vaccine.

PMID- 30119673
TI  - The reporting of funding in health policy and systems research: a cross-sectional
      study.
AB  - BACKGROUND: Major research-reporting statements, such as PRISMA and CONSORT,
      require authors to provide information about funding. The objectives of this
      study were (1) to assess the reporting of funding in health policy and systems
      research (HPSR) papers and (2) to assess the funding reporting policies of
      journals publishing on HPSR. METHODS: We conducted two cross-sectional surveys
      for papers published in 2016 addressing HPSR (both primary studies and systematic
      reviews) and for journals publishing on HPSR (both journals under the 'Health
      Policy and Services' (HPS) category in the Web of Science, and non-HPS journals
      that published on HPSR). Teams of two reviewers selected studies and abstracted
      data in duplicate and independently. We conducted descriptive analyses and a
      regression analysis to investigate the association between reporting of funding
      by papers and the journal's characteristics. RESULTS: We included 400 studies
      (200 systematic reviews and 200 primary studies) that were published in 198
      journals. Approximately one-third (31%) of HPSR papers did not report on funding.
      Of those that did, only 11% reported on the role of funders (15% of systematic
      reviews and 7% of primary studies). Of the 198 journals publishing on HPSR, 89%
      required reporting of the source of funding. Of those that did, about one-third
      (34%) required reporting of the role of funders. Journals classified under the
      HPS category (n = 72) were less likely than non-HPS journals that published HPSR
      studies (n = 142) to require information on the role of funders (15% vs. 32%). We
      did not find any of the journals' characteristics to be associated with the
      reporting of funding by papers. CONCLUSIONS: Despite the majority of journals
      publishing on HPSR requiring the reporting of funding, approximately one-third of
      HPSR papers did not report on the funding source. Moreover, few journals
      publishing on HPSR required the reporting of the role of funders, and few HPSR
      papers reported on that role.

PMID- 30119674
TI  - A novel method for transforming the thermophilic bacterium Geobacillus
      kaustophilus.
AB  - BACKGROUND: Bacterial strains of the genus Geobacillus grow at high temperatures
      of 50-75  degrees C and could thus be useful for biotechnological applications.
      However, genetic manipulation of these species is difficult because the current
      techniques for transforming Geobacillus species are not efficient. In this study,
      we developed an easy and efficient method for transforming Geobacillus
      kaustophilus using the conjugative plasmid pLS20cat. RESULTS: We constructed a
      transformation system comprising (i) a mobilizable Bacillus subtilis-G.
      kaustophilus shuttle plasmid named pGK1 that carries the elements for selection
      and replication in Geobacillus, and (ii) a pLS20cat-harboring B. subtilis donor
      strain expressing the dam methylase gene of Escherichia coli and the conjugation
      stimulating rapLS20 gene of pLS20cat. This system can be used to efficiently
      introduce pGK1 into G. kaustophilus by mobilization in a pLS20cat-dependent way.
      Whereas the thermostable kanamycin marker and Geobacillus replication origin of
      pGK1 as well as expression of dam methylase in the donor were indispensable for
      mobilization, ectopic expression of rapLS20 increased its efficiency. In
      addition, the conditions of the recipient influenced mobilization efficiency: the
      highest mobilization efficiencies were obtained using recipient cells that were
      in the exponential growth phase. Furthermore, elimination of the origin of
      transfer from pLS20cat enhanced the mobilization. CONCLUSIONS: We describe a
      novel method of plasmid mobilization into G. kaustophilus recipient from B.
      subtilis donor depending on the helper function of pLS20cat, which enables
      simple, rapid, and easy transformation of the thermophilic Gram-positive
      bacterium.

PMID- 30119675
TI  - Tip110/SART3 regulates IL-8 expression and predicts the clinical outcomes in
      melanoma.
AB  - Tip110, an important regulator of several oncogenic proteins, was significantly
      downregulated in human metastatic melanoma cells exposed to a hypoxic condition.
      Therefore, in this study, we set to determine whether differential expression of
      Tip110 could be an important indicator for melanoma tumorigenesis and metastasis.
      We found that in melanoma, but not in other cancer types, Tip110 knockdown
      enhanced significant expression and secretion of IL-8 and melanoma cells
      invasions. This induction was further potentiated under hypoxia and by
      inflammatory cytokine and found independent of TNF-alpha autocrine signaling. We
      further showed that Tip110 knockdown-mediated IL-8 induction involved IL-8 mRNA
      stability. Furthermore, the transcriptomic profiling data and survival from 455
      melanoma patients demonstrated that the correlation between Tip110 expression and
      the clinical outcomes in melanoma was stage-dependent. These findings uncover
      important roles of Tip110 in melanoma tumorigenesis and metastasis through
      regulation of IL-8 and hope to provide new clues for future therapeutic
      strategies.

PMID- 30119676
TI  - The contribution of Cyprus to non-communicable diseases and biomedical research
      from 2002 to 2013: implications for evidence-based health policy.
AB  - BACKGROUND: Non-communicable diseases (NCDs) are the leading causes of disease
      burden and mortality at the European level and in Cyprus. This research was
      conducted to map the research activities of Cypriot institutions in five NCDs,
      namely oncology, cardiovascular diseases, diabetes, mental health and respiratory
      conditions. METHODS: For the period 2002-2013, research in Cyprus was assessed on
      its biomedical outputs and compared to the rest of Europe relative to their GDP.
      The research output in the five NCDs was obtained and contrasted to their
      respective disease burdens. The results from each of the five NCDs showed the
      amount of cross-country collaboration with other researchers from other European
      countries and from the rest of the world, and the research level of the papers on
      a clinical to basic scale. For each NCD field the research application was
      assessed, whereas for oncology the research type was also assessed. Information
      was collected on the development of clinical guidelines, on Cypriot newspapers
      reporting on medical and policy documents and advisory committees' output as well
      as research and funding organisations available in Cyprus, for potential
      evaluation of impact in health policy on the five NCDs. RESULTS: Cypriot
      biomedical research output appeared appropriate in volume compared with its
      wealth and the expected value from a regression line for other European
      countries. However, it was focused particularly on the molecular mechanisms of
      transmittable or hereditary diseases, rather than on the five NCDs. Cyprus
      performs well in palliative care, which receives funding from several local
      charities and other non-profit organisations. Cyprus has the highest relative
      burden from diabetes in Europe, but the subject is largely neglected by
      researchers. Similarly, it suffers more from mental disorders than most of the
      rest of Europe, but the amount of research is relatively small. Respiratory
      conditions research is under-funded and under-researched too. CONCLUSIONS: The
      biomedical research portfolio in Cyprus is adequate in volume, but not well
      fitted to its pattern of disease. The means whereby research can be used to
      improve healthcare in the country are also unsatisfactory, although the Ministry
      of Health is now developing a comprehensive plan which will include the
      development of clinical guidelines and proposals for the evaluation of how
      healthcare is delivered on the island.

PMID- 30119677
TI  - Six-month safety evaluation of robenacoxib tablets (OnsiorTM) in dogs after daily
      oral administrations.
AB  - BACKGROUND: Robenacoxib is a non-steroidal anti-inflammatory drug available for
      canine and feline use for the control of pain and inflammation marketed as
      OnsiorTM. The aim of this target animal safety study was to evaluate the 6-month
      safety profile of oral robenacoxib administration. It was a randomized, negative
      controlled, parallel group study. Thirty-two healthy, young, experimentally
      naive, purebred Beagle dogs were administered 0 (sham control, Group 1), 2, 6,
      and 10 mg/kg robenacoxib (corresponding to the upper end of the dosage range [1X,
      Group 2] and multiples thereof [3X and 5X, Group 3 and 4]), orally once daily for
      6 months. Assessment of safety included general health and clinical observations,
      physical, neurological, ophthalmological and electrocardiographic examinations,
      gross and histopathological examinations and clinical pathology evaluations.
      Blood samples were collected for toxicokinetic assessment of robenacoxib.
      RESULTS: No serious adverse events were reported. When compared with control, no
      treatment effect was observed for body weight, feed or water consumption,
      clinical pathology, urinalysis and fecal examination parameters. There were no
      treatment-related changes in stifle joint tissues and microscopic/histopathology
      examinations of all tissues/organs were normal. Salivation and soft feces were
      noted in all groups but observed more frequently in the treated groups as
      compared with control. On Day 178, increased buccal mucosal bleeding times were
      observed in two treated animals (Group 3 and 4) and one dog in Group 4 displayed
      a retinal change. Decreased hopping and conscious proprioception was noted in
      four treated dogs. One dog in Group 2 had ventricular premature complexes. Post
      mortem changes included mild, red foci on the cecum in one dog (Group 3) and
      minimal duodenal discoloration in one dog (Group 4), with no corresponding
      histological findings in either dog. Ovarian weights were decreased in females
      from Group 3 and 4 with no gross or histological changes in the ovaries. Blood
      concentrations of robenacoxib confirmed systemic exposure of treated dogs.
      Exposure increased with increasing doses and there were no accumulation of
      robenacoxib in blood. CONCLUSIONS: Robenacoxib was well tolerated at doses from 2
      to 10 mg/kg/day and this 6-month study supports the safe use of OnsiorTM
      (robenacoxib) tablets in dogs for the intended dosing regimen.

PMID- 30119680
TI  - lncRNA KRAL reverses 5-fluorouracil resistance in hepatocellular carcinoma cells
      by acting as a ceRNA against miR-141.
AB  - BACKGROUND: 5-Fluorouracil (5-FU) has been widely applied to treat various types
      of cancers, including hepatocellular carcinoma (HCC). However, primary or
      acquired 5-FU resistance prevents the clinical application of this drug in cancer
      therapy. Herein, our study is the first to demonstrate that lower expression of
      KRAL, a long non-coding RNA (lncRNA), mediates 5-FU resistance in HCC via the miR
      141/Keap1 axis. METHODS: Cell proliferation assays, western blot analysis, qRT
      PCR, the dual-luciferase reporter assay and RNA immunoprecipitation were
      performed to investigate the mechanisms by which KRAL mediates 5-fluorouracil
      resistance in HCC cell lines. RESULTS: The quantitative analysis indicated that
      KRAL and Keap1 were significantly decreased and that Nrf2 was increased in
      HepG2/5-FU and SMMC-7721/5-FU cells compared with the corresponding expression
      levels in the respective parental cells. Overexpression of KRAL increased Keap1
      expression, and inactivating the Nrf2-dependent antioxidant pathway could reverse
      the resistance of HepG2/5-FU and SMMC-7721/5-FU cells to 5-FU. Moreover, KRAL
      functioned as a competitive endogenous RNA (ceRNA) by effectively binding to the
      common miR-141 and then restoring Keap1 expression. These findings demonstrated
      that KRAL is an important regulator of Keap1; furthermore, the ceRNA network
      involving KRAL may serve as a treatment strategy against 5-FU resistance in
      hepatocellular carcinoma cells. CONCLUSIONS: KRAL/miR-141/Keap1 axis mediates 5
      fluorouracil resistance in HCC cell lines.

PMID- 30119681
TI  - The expression signature of very long non-coding RNA in myalgic
      encephalomyelitis/chronic fatigue syndrome.
AB  - BACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a
      chronic debilitating disease with huge social-economic impact. It has been
      suggested that immune dysregulation, nitrooxidative stress, and metabolic
      impairment might contribute to disease pathogenesis. However, the etiology of
      ME/CFS remains largely unclear, and diagnostic/prognostic disease markers are
      lacking. Several long noncoding RNAs (lncRNA, > 200 bp) have been reported to
      play roles in immunological diseases or in stress responses. METHODS: In our
      study, we examined the expression signature of 10 very long lncRNAs (> 5 kb,
      CR933609, His-RNA, AK124742, GNAS1-AS, EmX2OS, MIAT, TUG1, NEAT1, MALAT1, NTT) in
      the peripheral blood mononuclear cells of 44 ME/CFS patients. RESULTS: LncRNAs
      NTT, MIAT and EmX2OS levels were found to be significantly elevated in ME/CFS
      patients as compared with healthy controls. Furthermore, NTT and EmX2OS levels
      increased with disease severity. Stimulation of human monocytic cell line THP-1
      and glioma cell line KALS1 with H2O2 (oxidative stress) and poly (I:C) (double
      strand RNA, representing viral activation) increased the expression levels of NTT
      and MIAT. CONCLUSIONS: Our study revealed a ME/CFS-associated very long lncRNA
      expression signature, which might reflect the regulatory response in ME/CFS
      patients to oxidative stress, chronic viral infection and hypoxemia. Further
      investigations need to be done to uncover the functions and potential diagnostic
      value of these lncRNAs in ME/CFS.

PMID- 30119678
TI  - Reawakening of dormant estrogen-dependent human breast cancer cells by bone
      marrow stroma secretory senescence.
AB  - BACKGROUND: Dormant estrogen receptor positive (ER+) breast cancer
      micrometastases in the bone marrow survive adjuvant chemotherapy and recur
      stochastically for more than 20 years. We hypothesized that inflammatory
      cytokines produced by stromal injury can re-awaken dormant breast cancer cells.
      METHODS: We used an established in vitro dormancy model of Michigan Cancer
      Foundation-7 (MCF-7) breast cancer cells incubated at clonogenic density on
      fibronectin-coated plates to determine the effects of inflammatory cytokines on
      reactivation of dormant ER+ breast cancer cells. We measured induction of a
      mesenchymal phenotype, motility and the capacity to re-enter dormancy. We induced
      secretory senescence in murine stromal monolayers by oxidation, hypoxia and
      estrogen deprivation with hydrogen peroxide (H2O2), carbonyl-cyanide m
      chlorophenylhydrazzone (CCCP) and Fulvestrant (ICI 182780), respectively, and
      determined the effects on growth of co-cultivated breast cancer cells. RESULTS:
      Exogenous recombinant human (rh) interleukin (IL)-6, IL-8 or transforming growth
      factor beta1 (TGFbeta1) induced regrowth of dormant MCF-7 cells on fibronectin
      coated plates. Dormant cells had decreased expression of E-cadherin and estrogen
      receptor alpha (ERalpha) and increased expression of N-cadherin and SNAI2 (SLUG).
      Cytokine or TGFbeta1 treatment of dormant clones induced formation of growing
      clones, a mesenchymal appearance, increased motility and an impaired capacity to
      re-enter dormancy. Stromal injury induced secretion of IL-6, IL-8, upregulated
      tumor necrosis factor alpha (TNFalpha), activated TGFbeta and stimulated the
      growth of co-cultivated MCF-7 cells. MCF-7 cells induced secretion of IL-6 and IL
      8 by stroma in co-culture. CONCLUSIONS: Dormant ER+ breast cancer cells have
      activated epithelial mesenchymal transition (EMT) gene expression programs and
      downregulated ERalpha but maintain a dormant epithelial phenotype. Stromal
      inflammation reactivates these cells, induces growth and a mesenchymal phenotype.
      Reactivated, growing cells have an impaired ability to re-enter dormancy. In
      turn, breast cancer cells co-cultured with stroma induce secretion of IL-6 and IL
      8 by the stroma, creating a positive feedback loop.

PMID- 30119679
TI  - Targeting the Tie2-alphavbeta3 integrin axis with bi-specific reagents for the
      inhibition of angiogenesis.
AB  - BACKGROUND: Increased activity of the receptor tyrosine kinase Tie2 has been
      implicated in the promotion of pathological angiogenesis. This activity is mainly
      mediated through angiopoietin (Ang)1- and Ang2-dependent activation of integrins
      by Tie2, rendering the Ang/Tie2/integrin axis an attractive putative target for
      cancer therapeutics. RESULTS: To target this axis, we developed single domain,
      non-immunoglobulin high-affinity bi-specific protein inhibitors against both Tie2
      and alphavbeta3 integrin. We have previously engineered the Ang2-binding domain
      of Tie2 (Ang2-BD) as a Tie2 inhibitor. Here, we engineered an exposed loop in
      Ang2-BD to generate variants that include an integrin-binding Arg-Gly-Asp (RGD)
      motif and used flow cytometry screening of a yeast-displayed Ang2-BD RGD loop
      library to identify the integrin antagonists. The bi-specific antagonists
      targeting both Tie2 and alphavbeta3 integrin inhibited adhesion and proliferation
      of endothelial cells cultured together with the alphavbeta3 integrin ligand
      vitronectin, as well as endothelial cell invasion and tube formation. The bi
      specific reagents inhibited downstream signaling by Tie2 intracellularly in
      response to its agonist Ang1 more effectively than the wild-type Ang2 BD that
      binds Tie2 alone. CONCLUSIONS: Collectively, this study-the first to describe
      inhibitors targeting all the known functions resulting from Tie2/integrin
      alphavbeta3 cross-talk-has created new tools for studying Tie2- and integrin
      alphavbeta3-dependent molecular pathways and provides the basis for the rational
      and combinatorial engineering of ligand-Tie2 and ligand-integrin alphavbeta3
      receptor interactions. Given the roles of these pathways in cancer angiogenesis
      and metastasis, this proof of principle study paves the route to create novel
      Tie2/integrin alphavbeta3-targeting proteins for clinical use as imaging and
      therapeutic agents.

PMID- 30119682
TI  - Vitamin D receptor polymorphism rs2228570 is significantly associated with risk
      of dyslipidemia and serum LDL levels in Chinese Han population.
AB  - BACKGROUND: The goal of this study was to determine if vitamin D receptor (VDR)
      gene polymorphisms underlie susceptibility to dyslipidemia in a Chinese Han
      population. METHODS: Three tag single nucleotide polymorphisms (SNPs)
      (rs11574129, rs2228570, and rs739837) were genotyped using TaqMan assays to
      determine VDR SNP associations with dyslipidemia. We genotyped 877 cases of
      dyslipidemia from a normotensive, non-diabetes mellitus population and 1822 non
      dyslipidemia subjects in a stage I study. In a follow-up stage II study, we
      included a larger sample of 3124 controls and 1679 cases with dyslipidemia.
      Finally, we explored the potential molecular mechanism for the SNP associations
      using molecular modeling analysis. RESULTS: We found a significant association
      between SNP rs2228570 and dyslipidemia in the additive (adjusted odds ratio (OR)
      = 1.255, 95% Confidence Interval (CI) = (1.118-1.409), P < 0.001), dominant (OR =
      1.384, 95% CI = 1.384 (1.136-1.6), P = 0.001) and recessive models (OR = 1.356,
      95%CI = 1.1-1.671, P = 0.004) in stage I. We further established that the
      rs2228570 variant was significantly associated with dyslipidemia in the additive
      (adjusted OR = 1.146, 95% CI = 1.053-1247, P = 0.002), dominant (OR = 1.184,
      95%CI =1.018-1.376, P = 0.028) and recessive models (OR = 1.209, 95%CI = 1.064
      1.374, P = 0.004) in stage II. The TT genotype was significantly higher (4.93 +/-
      0.75 mmol/L) compared to the TC (4.67 +/- 0.47 mmol/L) or CC (4.66 +/- 0.44
      mmol/L) genotype (P = 0.01) in cases with elevated low-density lipoprotein
      cholesterol (LDL-C) levels. In contrast, the cases with the TT genotype had
      significantly lower serum 25(OH)D levels (18.43 +/- 5.04 ng/ mL) compared to the
      TC (26.24 +/- 4.16 ng/mL) and CC (36.76 +/- 8.10 ng/ mL) genotypes (P < 0.001).
      Multivariable linear regression analysis indicated that the rs2228750 genotype
      significantly correlated with serum low-density lipoprotein-C (LDL-C) levels in
      cases with dyslipidemia. Using molecular modeling analysis, we further found that
      the rs2228570 variant changed the structure and the stability of VDR and altered
      the binding energy of its ligand. CONCLUSIONS: The VDR rs2228570 variant may
      increase susceptibility to dyslipidemia in the Chinese Han population.

PMID- 30119683
TI  - The relationship between apolipoprotein genes polymorphisms and susceptibility to
      osteonecrosis of the femoral head: a meta-analysis.
AB  - BACKGROUND: The objective of this study was to evaluate whether apolipoprotein
      gene polymorphisms confer susceptibility to osteonecrosis of the femoral head
      (ONFH). METHODS: The relevant literature was screened from databases of Pubmed,
      Embase, Wanfang, Weipu and China National Knowledge Internet (CNKI) until May,
      2017. In addition, odds ratio (OR) and its corresponding 95% confidence interval
      (CI) were used as a measure of effect size for calculating effect size. RESULTS:
      Totally, six case-control studies were included in this meta-analysis. It
      revealed that ApoB-C7623T polymorphism frequency was increased in ONFH group than
      in control group under three genetic models, including allele model (T vs. C, OR
      = 4.5149, 95% CI: 1.6968-12.0134); additive model (TC vs. CC, OR = 6.2515, 95%
      CI: 2.0939-18.6640); and dominant model (TT + TC vs. CC, OR = 5.4998, 95% CI:
      1.9246-15.7163). In addition, the increased risk of ONFH were related to ApoA1
      rs1799837 polymorphism under additive model (AA vs. GG, OR = 1.4175, 95% CI:
      1.0522-1.9096) and recessive model (AA vs. GG + AG, OR = 1.7727, 95% CI: 1.3399
      2.3452). However, four ApoB rs1042031, rs693, 3'-VNTR and G12619A polymorphisms
      under the all genetic models were not associated with susceptibility to ONFH.
      CONCLUSION: The T allele and TC genotype of ApoB-C7623T and AA genotype of ApoA1
      rs1799837 may contribute to increase the risk of ONFH.

PMID- 30119684
TI  - The role of definitive chemoradiotherapy versus surgery as initial treatments for
      potentially resectable esophageal carcinoma.
AB  - BACKGROUND: We performed a meta-analysis to compare the efficacy of definitive
      chemoradiotherapy (dCRT) and esophagectomy as initial treatments for potentially
      resectable esophageal cancer. METHODS: To assess both strategies, the combined
      odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Thirteen
      studies (N = 2071; dCRT = 869 and surgery = 1202) were included. In all, 90.39%
      of the patients were diagnosed with esophageal squamous cell carcinoma (ESCC).
      RESULTS: The 2-year (OR = 1.199, 95% CI 0.922-1.560; P = 0.177) and 5-year
      overall survival (OS) rates (OR = 0.947, 95% CI 0.628-1.429; P = 0.796) were not
      significantly different. No significant differences were identified in the 2-year
      OS among patients with stage I disease (OR = 1.397, 95% CI 0.740-2.638; P =
      0.303) or stage II-III (OR = 0.418, 95% CI 0.022-7.833; P = 0.560). Patients with
      lymph node metastases tended to have a better 5-year OS when treated with dCRT
      than with surgery (OR = 0.226, 95% CI 0.044-1.169; P = 0.076); however, the
      difference between the two methods was not significant. Western patients who
      received dCRT had poorer prognoses than patients who underwent surgery (OR =
      1.522, 95% CI 1.035-2.238; P = 0.033). dCRT and surgery led to similar 5-year
      progression-free survival rates (OR = 1.06, 95% CI 0.79-1.42; P = 0.70).
      CONCLUSIONS: dCRT and surgery are equally effective as initial treatments for
      potentially resectable esophageal cancer. These results apply primarily to Asian
      populations as they have an increased incidence of ESCC.

PMID- 30119685
TI  - Culicoides species composition and abundance on Irish cattle farms: implications
      for arboviral disease transmission.
AB  - BACKGROUND: Following the emergence of Schmallenberg virus (SBV) in Ireland in
      2012, a sentinel herd surveillance program was established in the south of
      Ireland with the primary aim of investigating the species composition and
      abundance of Culicoides on livestock farms in the region. METHODS: Ultraviolet
      light trapping for Culicoides was carried out on 10 sentinel farms. Each site was
      sampled fortnightly over 16 weeks (21st July to 5th November 2014). One
      Onderstepoort Veterinary Institute UV light trap was run overnight at each site
      and catches were transferred immediately into 70% ethanol. Culicoides were
      morphologically identified to species level. Collection site habitats were
      characterised using the Phase 1 habitat survey technique (Joint Nature
      Conservation Committee). RESULTS: A total of 23,929 individual Culicoides from 20
      species was identified, including one species identified in Ireland for the first
      time, Culicoides cameroni. The most abundant species identified were Culicoides
      obsoletus/Culicoides scoticus (38%), Culicoides dewulfi (36%), Culicoides
      pulicaris (9%), Culicoides chiopterus (5%) and Culicoides punctatus (5%),
      comprising 93% of all Culicoides specimens identified. Collection site habitats
      were dominated by improved grassland and a combination of broadleaf woodland and
      native woodland species. CONCLUSIONS: The most abundant species of Culicoides
      identified were the putative vectors of bluetongue virus (BTV) and SBV in
      northern Europe. Their presence and abundance demonstrates the potential for
      future transmission of arboviruses among livestock in this region.

PMID- 30119687
TI  - Chest radiography versus lung ultrasound for identification of acute respiratory
      distress syndrome: a retrospective observational study.
AB  - BACKGROUND: Lung ultrasound may be a reasonable alternative to chest radiography
      for the identification of acute respiratory distress syndrome (ARDS), but the
      diagnostic performance of lung ultrasound for ARDS is uncertain. We therefore
      analyzed the clinical outcomes of ARDS diagnosed according to the Berlin
      Definition, using either chest radiography (Berlin-CXR) or lung ultrasound
      (Berlin-LUS) as an alternative imaging method. METHODS: This was a retrospective
      observational study in a 20-bed medical intensive care unit (ICU). Patients who
      required noninvasive ventilation or invasive ventilation for hypoxemic
      respiratory failure on ICU admission from August 2014 to March 2017 were
      included. Both chest radiography and lung ultrasound were performed routinely
      upon ICU admission. Comparisons were made using either the Berlin-CXR or Berlin
      LUS definitions to diagnose ARDS with respect to the patient characteristics and
      clinical outcomes for each definition. ICU and hospital mortality were the main
      outcome measures for both definitions. RESULTS: The first admissions of 456
      distinct patients were analyzed. Compared with the 216 patients who met the
      Berlin-CXR definition (ICU mortality 19.4%, hospital mortality 36.1%), 229
      patients who met the Berlin-LUS definition (ICU mortality 22.7%, hospital
      mortality 34.5%) and 79 patients who met the Berlin-LUS but not the Berlin-CXR
      definition (ICU mortality 21.5%, hospital mortality 29.1%) had similar outcomes.
      In contrast, the 295 patients who met either definition had higher mortality than
      the 161 patients who did not meet either definition (ICU mortality 20.0% versus
      12.4%, P = 0.041; hospital mortality 34.2% versus 24.2%, P = 0.027). Compared
      with Berlin-CXR, Berlin-LUS had a positive predictive value of 0.66 (95%
      confidence interval 0.59-0.72) and a negative predictive value of 0.71 (0.65
      0.77). Among the 216 Berlin-CXR ARDS patients, 150 patients (69.4%) also
      fulfilled Berlin-LUS definition. CONCLUSIONS: For the identification of ARDS
      using the Berlin definition, both chest radiography and lung ultrasound were
      equally related to mortality. The Berlin definition using lung ultrasound helped
      identify patients at higher risk of death, even if these patients did not fulfill
      the conventional Berlin definition using chest radiography. However, the moderate
      overlap of patients when chest imaging modalities differed suggests that chest
      radiography and lung ultrasound should be complementary rather than used
      interchangeably.

PMID- 30119688
TI  - Sub-retinal abscess as presenting feature of endogenous Candida endophthalmitis.
AB  - BACKGROUND: Sub-retinal abscess as the presenting feature in the setting of
      endogenous fungal endophthalmitis is extremely infrequent. Immunodeficiency
      states are major predisposing risk factors. To the best of our knowledge, this is
      the first case report of Candida sub-retinal abscess as initial presentation in
      an immunocompetent patient. CASE PRESENTATION: A 32-year old, generally fit and
      well, female presented to us with gradually deteriorating vision in her right
      eye. Visual acuity was counting fingers in the right eye and, 20/30 in the left
      eye. Right eye fundus examination showed a full thickness, yellowish-white foveal
      lesion, and significant vitreous haze. Left eye examination was normal. Upon
      direct questioning, the patient disclosed history of backstreet abortion 3 weeks
      prior to the onset of her ocular symptoms. She underwent vitreous tap and
      intravitreal antibiotics (amphotericin B, 5 MUg/0.5 ml). Vitreous culture showed
      profuse growth of Candida albicans. Because her condition was progressively
      deteriorating, she underwent 25 g vitrectomy plus repeat intravitreal
      amphotericin B under general anaesthesia. Three weeks post-vitrectomy, vitreous
      inflammation resolved completely, and the sub-retinal abscess healed with a
      macular scar formation. Over a follow-up of 4 years, no recurrences were
      observed. CONCLUSION: Our case highlights the importance of considering Candida
      albicans infection in the differential diagnosis of sub-retinal abscesses.
      Although immunocompromised states are traditionally identified as predisposing
      factors for fungal infections, fungal endogenous endophthalmitis can occur in
      healthy individuals as well.

PMID- 30119686
TI  - Functional outcomes in adults with tuberculous meningitis admitted to the ICU: a
      multicenter cohort study.
AB  - BACKGROUND: Tuberculous meningitis (TBM) is a devastating infection in
      tuberculosis endemic areas with limited access to intensive care. Functional
      outcomes of severe adult TBM patients admitted to the ICU in nonendemic areas are
      not known. METHODS: We conducted a retrospective multicenter cohort study (2004
      2016) of consecutive TBM patients admitted to 12 ICUs in the Paris area, France.
      Clinical, biological, and brain magnetic resonance imaging (MRI) findings at
      admission associated with a poor functional outcome (i.e., a score of 3-6 on the
      modified Rankin scale (mRS) at 90 days) were identified by logistic regression.
      Factors associated with 1-year mortality were investigated by Cox proportional
      hazards modeling. RESULTS: We studied 90 patients, of whom 61 (68%) had a score
      on the Glasgow Coma Scale <= 10 at presentation and 63 (70%) required invasive
      mechanical ventilation. Brain MRI revealed infarction and hydrocephalus in 38/75
      (51%) and 25/75 (33%) cases, respectively. A poor functional outcome was observed
      in 55 (61%) patients and was independently associated with older age (adjusted
      odds ratio (aOR) 1.03, 95% CI 1.0-1.07), cerebrospinal fluid protein level >= 2
      g/L (aOR 5.31, 95% CI 1.67-16.85), and hydrocephalus on brain MRI (aOR 17.2, 95%
      CI 2.57-115.14). By contrast, adjunctive steroids were protective (aOR 0.13, 95%
      CI 0.03-0.56). The multivariable adjusted hazard ratio of adjunctive steroids for
      1-year mortality (47%, 95% CI 37%-59%) was 0.23 (95% CI 0.11-0.44). Among
      survivors at 1 year, functional independence (mRS of 0-2) was observed in 27/37
      (73%, 95% CI 59%-87%) cases. CONCLUSIONS: A poor functional outcome in adult TBM
      patients admitted to the ICU in a nonendemic area is observed in 60% of cases and
      is independently associated with elevated cerebrospinal fluid protein level and
      hydrocephalus. Our data also suggest a protective effect of adjunctive steroids,
      with reduced disability and mortality, irrespective of immune status and severity
      of disease at presentation. One-year follow-up revealed functional independence
      in most survivors.

PMID- 30119689
TI  - JARID2 and the PRC2 complex regulate skeletal muscle differentiation through
      regulation of canonical Wnt signaling.
AB  - BACKGROUND: JARID2 is a non-catalytic member of the polycomb repressive complex 2
      (PRC2), which is known to regulate developmental target genes in embryonic stem
      cells. Here, we provide mechanistic insight into the modulation of Wnt signaling
      by JARID2 during murine skeletal muscle differentiation. RESULTS: We show that
      JARID2 is expressed in proliferating myoblasts, but downregulated upon muscle
      differentiation. Unexpectedly, depletion of JARID2 or the catalytic subunit of
      the PRC2 complex, EZH2, inhibited differentiation, suggesting that JARID2 and the
      PRC2 complex are required to initiate this process. Expression of the myogenic
      regulatory factors required to promote differentiation, MYOD and MYOG, was
      downregulated in the absence of JARID2, even though decreases in the methylation
      of histone H3 lysine 27 (H3K27me3) were observed on both promoters. We found that
      activation of the Wnt signaling pathway upregulated MYOD and restored
      differentiation. Activation of the Wnt pathway in JARID2 depleted cells caused
      beta-catenin to translocate to the nucleus, where it bound to and activated the
      Myod1 promoter. We show that the Wnt antagonist SFRP1 is highly upregulated in
      the absence of JARID2 and is a direct target of JARID2 and the PRC2 complex.
      Ectopic expression of SFRP1 blocked MYOD and late muscle gene expression and
      inhibited the translocation of beta-catenin to the nucleus. Finally, we show that
      JARID2 and SFRP1 are inversely correlated in melanoma, confirming that the JARID2
      mediated repression of SFRP1 extends beyond skeletal muscle and has important
      implications in many cellular systems, including cancer. CONCLUSIONS: We show
      that JARID2 and the PRC2 complex regulate muscle differentiation by modulating
      Wnt signaling through the direct repression of Wnt antagonists.

PMID- 30119690
TI  - Functional CRISPR screen identifies AP1-associated enhancer regulating FOXF1 to
      modulate oncogene-induced senescence.
AB  - BACKGROUND: Functional characterization of non-coding elements in the human
      genome is a major genomic challenge and the maturation of genome-editing
      technologies is revolutionizing our ability to achieve this task. Oncogene
      induced senescence, a cellular state of irreversible proliferation arrest that is
      enforced following excessive oncogenic activity, is a major barrier against
      cancer transformation; therefore, bypassing oncogene-induced senescence is a
      critical step in tumorigenesis. Here, we aim at further identification of
      enhancer elements that are required for the establishment of this state. RESULTS:
      We first apply genome-wide profiling of enhancer-RNAs (eRNAs) to systematically
      identify enhancers that are activated upon oncogenic stress. DNA motif analysis
      of these enhancers indicates AP-1 as a major regulator of the transcriptional
      program induced by oncogene-induced senescence. We thus constructed a CRISPR-Cas9
      sgRNA library designed to target senescence-induced enhancers that are putatively
      regulated by AP-1 and used it in a functional screen. We identify a critical
      enhancer that we name EnhAP1-OIS1 and validate that mutating the AP-1 binding
      site within this element results in oncogene-induced senescence bypass.
      Furthermore, we identify FOXF1 as the gene regulated by this enhancer and
      demonstrate that FOXF1 mediates EnhAP1-OIS1 effect on the senescence phenotype.
      CONCLUSIONS: Our study elucidates a novel cascade mediated by AP-1 and FOXF1 that
      regulates oncogene-induced senescence and further demonstrates the power of
      CRISPR-based functional genomic screens in deciphering the function of non-coding
      regulatory elements in the genome.

PMID- 30119691
TI  - Predicting acute kidney injury using urinary liver-type fatty-acid binding
      protein and serum N-terminal pro-B-type natriuretic peptide levels in patients
      treated at medical cardiac intensive care units.
AB  - BACKGROUND: The early prediction of acute kidney injury (AKI) can facilitate
      timely intervention and prevent complications. We aimed to understand the
      predictive value of urinary liver-type fatty-acid binding protein (L-FABP) levels
      on admission to medical (non-surgical) cardiac intensive care units (CICUs) for
      AKI, both independently and in combination with serum N-terminal pro-B-type
      natriuretic peptide (NT-proBNP) levels. METHODS: We prospectively investigated
      the predictive value of L-FABP and NT-proBNP for AKI in a large, heterogeneous
      cohort of patients treated in medical CICUs. Baseline urinary L-FABP and serum NT
      proBNP were measured on admission. AKI was diagnosed according to the Kidney
      Disease: Improving Global Outcomes criteria. We studied 1273 patients (mean age,
      68 years), among whom 46% had acute coronary syndromes, 38% had acute
      decompensated heart failure, 5% had arrhythmia, 3% had pulmonary hypertension, 2%
      had acute aortic syndrome, 2% had infective endocarditis, and 1% had Takotsubo
      cardiomyopathy. RESULTS: Urinary L-FABP levels correlated with serum NT-proBNP
      levels (r = 0.17, p < 0.0001). AKI occurred in 224 patients (17.6%), including 48
      patients with stage 2 or 3 disease. Patients who developed AKI had higher one
      week and 6-month mortality than those who did not develop AKI (p = 0.0002 and p =
      0.003, respectively). In the multivariate logistic analysis, both L-FABP (p <
      0.0001) and NT-proBNP (p = 0.006) were independently associated with the
      development of AKI. Adding L-FABP and NT-proBNP to a baseline model that included
      established risk factors further improved reclassification (p < 0.001) and
      discrimination (p < 0.01) beyond that of the baseline model or any single
      biomarker individually. CONCLUSIONS: Urinary L-FABP and serum NT-proBNP levels on
      admission are independent predictors of AKI, and when used in combination,
      improve early prediction of AKI in patients hospitalized at medical CICUs.

PMID- 30119692
TI  - Carbon dioxide dynamics in relation to neurological outcome in resuscitated out
      of-hospital cardiac arrest patients: an exploratory Target Temperature Management
      Trial substudy.
AB  - BACKGROUND: Dyscarbia is common in out-of-hospital cardiac arrest (OHCA) patients
      and its association to neurological outcome is undetermined. METHODS: This is an
      exploratory post-hoc substudy of the Target Temperature Management (TTM) trial,
      including resuscitated OHCA patients, investigating the association between
      serial measurements of arterial partial carbon dioxide pressure (PaCO2) and
      neurological outcome at 6 months, defined by the Cerebral Performance Category
      (CPC) scale, dichotomized to good outcome (CPC 1 and 2) and poor outcome (CPC 3
      5). The effects of hypercapnia and hypocapnia, and the time-weighted mean PaCO2
      and absolute PaCO2 difference were analyzed. Additionally, the association
      between mild hypercapnia (6.0-7.30 kPa) and neurological outcome, its interaction
      with target temperature (33  degrees C and 36  degrees C), and the association
      between PaCO2 and peak serum-Tau were evaluated. RESULTS: Of the 939 patients in
      the TTM trial, 869 were eligible for analysis. Ninety-six percent of patients
      were exposed to hypocapnia or hypercapnia. None of the analyses indicated a
      statistical significant association between PaCO2 and neurological outcome (P =
      0.13-0.96). Mild hypercapnia was not associated with neurological outcome (P =
      0.78) and there was no statistically significant interaction with target
      temperature (Pinteraction = 0.95). There was no association between PaCO2 and
      peak serum-Tau levels 48 or 72 h after return of spontaneous circulation (ROSC).
      CONCLUSIONS: Dyscarbia is common after ROSC. No statistically significant
      association between PaCO2 in the post-cardiac arrest phase and neurological
      outcome at 6 months after cardiac arrest was detected. There was no significant
      interaction between mild hypercapnia and temperature in relation to neurological
      outcome.

PMID- 30119693
TI  - A qualitative study of refugee families' experiences of the escape and travel
      from Syria to Sweden.
AB  - OBJECTIVE: Research shows that, depending on the route of travel during the
      escape, the journey presents the refugees with different health risks. Traumatic
      events during flight may have long-lasting physical and psychological effects on
      the refugee children. Therefore, it is important to illuminate the experiences
      that refugee families arriving in Sweden have endured during their flight. A
      qualitative study was conducted through interviews with fifteen recently arrived
      Syrian refugee families. RESULTS: The parents described different reasons as to
      why they as families had to escape the war. Some families had lost jobs and loved
      ones in the war and did not want their children to die as well. They mentioned
      that the journeys varied between 10 and 40 days and were usually filled with
      struggles and threats. The escape to Sweden was expressed as an emotionally
      trying journey. Many parents talked about the fear and terror the children felt.
      Traumatic events during the escape, such as separation from family, death of
      family members, sexual violence, kidnapping or extortion may have long-lasting
      physical and psychological effects on the refugee children and their families.
      Therefore, health care workers meeting and caring for these families after
      arrival must pay close attention to that.

PMID- 30119695
TI  - p53 activation: a checkpoint for precision genome editing?

PMID- 30119694
TI  - Buying time: a proof-of-concept randomized controlled trial to improve sleep
      quality and cognitive function among older adults with mild cognitive impairment.
AB  - BACKGROUND: Current evidence suggests that good quality sleep is associated with
      preserved cognitive function and reduced dementia risk in older adults. Sleep
      complaints are especially common among older adults with mild cognitive
      impairment (MCI), and this may contribute to their increased risk for progression
      to dementia. Thus, improving their sleep may be important for maintaining their
      cognitive health. Chronotherapy is a set of intervention strategies that can
      improve sleep quality through strengthening the entrainment of the biological
      clock to the solar light-dark cycle, and includes strategies such as (1) bright
      light therapy (BLT); (2) physical activity (PA); and (3) good sleep hygiene. Of
      these strategies, BLT is the most potent and is based on providing individualized
      timing to entrain circadian rhythms. Thus, a personalized chronotherapy
      intervention of individually timed BLT and individually tailored PA promotion, in
      conjunction with general sleep hygiene education may promote older adult sleep
      quality. We therefore aim to carry out a proof-of-concept randomized controlled
      trial (RCT) to examine the efficacy of such a personalized chronotherapy
      intervention to improve sleep quality among older adults with MCI.
      METHODS/DESIGN: This was a 24-week RCT of a personalized chronotherapy
      intervention aimed to primarily improve sleep quality as measured by the
      MotionWatch8(c). Participants in the personalized chronotherapy group (INT) will
      receive four once-weekly, general sleep hygiene education classes, followed by 20
      weeks of (1) individually timed BLT and (2) bi-weekly, individually tailored PA
      counseling phone calls in conjunction with receiving a consumer-available PA
      tracker-the Fitbit(r) FlexTM. Ninety-six adults (aged 65-85 years) classified as
      having MCI (i.e., Mini-Mental State Exam (MMSE) >= 24; Montreal Cognitive
      Assessment (MoCA) <= 26; without dementia or significant functional impairment)
      will be randomized to either INT or a waitlist control group (CON). DISCUSSION:
      The results of this trial will help determine if a personalized chronotherapy
      intervention that includes individually timed BLT and individually tailored PA
      promotion, along with general sleep hygiene education can promote sleep quality
      among older adults at increased risk for dementia. Our results will help inform
      best practices for promoting sleep quality among older adults with MCI. TRIAL
      REGISTRATION: ClinicalTrials.gov , NCT02926157 . Registered on 6 October 2016.

PMID- 30119696
TI  - Ocular bacterial infections and antibiotic resistance patterns in patients
      attending Gondar Teaching Hospital, Northwest Ethiopia.
AB  - OBJECTIVES: Empirical selections of antimicrobial therapy based on clinical
      observations are common clinical practices in Ethiopia. This study identified
      common external ocular infections and determined antibiotic susceptibility
      testing in northwest Ethiopia. RESULTS: Among 210 patients studied,
      conjunctivitis 32.9%(69), blepharitis 26.7%(56), dacryocystitis 14.8%(51),
      blepharoconjunctivitis 11.9%(25), and trauma 10.0%(21) were the most common
      external ocular infections. Pathogenic bacteria were isolated among 62.4%(131)
      cases. The distributions of bacteria detected in conjunctivitis, dacryocystitis,
      and blepharitis patients were 32.8%(43), 23.7%(31), and 16.0%(21), respectively.
      The most prevalent isolates were coagulase negative Staphylococci; 27.5%(36), S.
      aureus; 26.7%(35), Pseudomonas species; 10.7%(14), and E. coli; 7.6%(10).
      Tetracycline, amoxicillin, chloramphenicol, ampicillin, and nalidic acid showed
      resistance to bacterial isolates with a respective prevalence of 35.9%(47),
      32.1%(42), 26.2%(34), 25.2%(33), and 23.7%(31). Multi-drug resistance patterns to
      the commonly prescribed antibiotics tested was 20.6%(27), 18.3%(24), 17.6%(23),
      5.3%(7), and 4.6%(6) to two, three, four, five, and six antibiotics,
      respectively. Overall, the multi-drug resistance prevalence rate was 66.4%(87).
      This study confirmed diverse types of external ocular manifestations associated
      with bacterial infections with wide ranges of antibiotic resistant phenotypes.
      Thus, combining clinical information, bacteriological analysis, and antimicrobial
      susceptibility tests are useful for making an evidence-based selection of
      antibiotics therapy.

PMID- 30119698
TI  - Synchronous double primary hepatic cancer consisting of hepatocellular carcinoma
      and cholangiolocellular carcinoma: a case report.
AB  - BACKGROUND: The incidence of synchronous double primary hepatic cancers is
      extremely low. Cholangiolocellular carcinoma is also a rare disease. CASE
      PRESENTATION: A 58-year-old Japanese man was referred to our hospital for the
      treatment of multiple liver tumors revealed on computed tomography scans. He was
      hepatitis B and C positive and had undergone hemodialysis for 9 years due to
      chronic renal failure. Computed tomography scans revealed two hepatic tumors
      (each <= 1.0 cm in diameter) in segments 3 and 7. The preoperative diagnosis was
      multiple hepatocellular carcinomas. He underwent partial resections of his liver.
      The resected specimens revealed that the tumors in segments 3 and 7 were well
      defined lesions of 8.0 mm and 14.0 mm, respectively. Pathological and
      immunohistochemical examinations confirmed the tumor in segment 3 to be a
      cholangiolocellular carcinoma and the tumor in segment 7 to be a hepatocellular
      carcinoma. Chronic inflammation could contribute to the different types of
      primary hepatic cancers. It may also give rise to various combinations of
      synchronous double primary hepatic cancer in patients with chronic liver disease.
      CONCLUSIONS: We describe the sixth case of synchronous double primary hepatic
      cancers consisting of hepatocellular carcinoma and cholangiolocellular carcinoma
      in chronic damaged liver and review the literature. In patients with chronic
      liver disease, careful surveillance with imaging studies should be mandatory as
      various types of primary hepatic cancers could develop.

PMID- 30119697
TI  - Effects of aerobic training on physical activity in people with stroke: protocol
      for a randomized controlled trial.
AB  - BACKGROUND: Post-stroke physical inactivity is explained by several factors
      related to the stroke, which have been suggested as the causes and consequences
      of functional declines and health problems. Therefore, it is important to
      increase physical activity levels and reduce the time spent in low-energy
      expenditure activities after a stroke. Since the maintenance of cardiorespiratory
      fitness is a significant predictor of physical activity levels post-stroke, it
      may be important to investigate whether aerobic training is effective in
      increasing physical activity levels and reducing the time spent in low-energy
      expenditure activities in this population. The efficacy of aerobic training on
      these variables is not well known. The primary objective of this trial will be to
      investigate the effects of aerobic treadmill training on physical activity levels
      and on time spent in low-energy expenditure activities in people with stroke. The
      secondary aim will be to evaluate the effects of the training on
      cardiorespiratory fitness, endurance, depression, mobility, quality of life, and
      participation. METHODS/DESIGN: A randomized controlled trial, with blinded
      assessments, will be performed in a community-based setting. Altogether, 22
      adults with a diagnosis of stroke (>6 months) who are sedentary or insufficiently
      active will be included. Participants will be randomly assigned to either: (1)
      aerobic treadmill training (experimental group, at 60-80% of their heart rate
      reserve) or (2) walking outside (control group, below 40% of heart rate reserve).
      Both groups will attend 40-min training sessions, three times per week over 12
      weeks, in groups of two to four participants, with a trained physiotherapist.
      Primary outcomes are physical activity levels and time spent in low-energy
      expenditure activities (Multi-sensor SenseWear Mini(r) and Human Activity
      Profile). Secondary outcomes are cardiorespiratory fitness (peak oxygen uptake
      VO2peak and ventilatory threshold), endurance, depression, mobility, quality of
      life, and participation. The effects of the training will be analyzed from the
      collected data using intention to treat. Between-group differences will be
      measured by two-way repeated measures ANOVA, considering the baseline, post
      training, and 4-week follow-up. DISCUSSION: The results of this trial will likely
      provide valuable new information on the effects of aerobic treadmill training on
      physical activity levels and on time spent in low-energy expenditure activities
      of individuals with stroke, through changes in cardiorespiratory fitness. TRIAL
      REGISTRATION: ClinicalTrials.gov, NCT02798237 . Registered on 13 June 2016.

PMID- 30119699
TI  - Histidine-rich glycoprotein as an excellent biomarker for sepsis and beyond.
AB  - Sepsis remains a critical problem with high morbidity and mortality worldwide.
      One of the problems we have in critical care is the need to find a good biomarker
      of sepsis to determine the existence of bacterial infection and the severity of
      patients. This would enable us to start appropriate treatment at an earlier stage
      of the disease course. We propose that decreases in the plasma protein histidine
      rich glycoprotein (HRG) is an excellent biomarker of sepsis compared with the
      current markers. Based on the novel pathophysiological roles of HRG in the
      cascade of events during sepsis, we also discuss the potential for supplemental
      therapy with purified HRG.

PMID- 30119701
TI  - The magnitude of anemia and associated factors among pregnant women attending
      public institutions of Shire Town, Shire, Tigray, Northern Ethiopia, 2018.
AB  - OBJECTIVE: Anemia is a widespread health problem among pregnant women causing
      maternal/infant morbidity and mortality mainly in low-income countries.
      Understanding of the magnitude of anemia and related socio-demographic variables
      in a specific setting would help scale-up preventive and therapeutic measures in
      a locality. So that this study focuses on the magnitude of anemia and its
      associated factor among pregnant women attending antenatal care in public
      hospitals of shire town and using institution based cross-sectional study design
      on 480 randomly selected study subjects. RESULT: The overall prevalence of anemia
      was 16.3%. Majority of the participants (52%) have mild anemia (10-10.9 gm/dl).
      Pregnant mothers with human immunodeficiency virus, intestinal parasitic
      infection and having lower inter-pregnancy gap were significant predictors of
      anemia. Preventing infection of the mother during pregnancy and making the gap
      between pregnancies are necessary.

PMID- 30119700
TI  - Integrating innovations: a qualitative analysis of referral non-completion among
      rapid diagnostic test-positive patients in Uganda's human African trypanosomiasis
      elimination programme.
AB  - BACKGROUND: The recent development of rapid diagnostic tests (RDTs) for human
      African trypanosomiasis (HAT) enables elimination programmes to decentralise
      serological screening services to frontline health facilities. However, patients
      must still undertake multiple onwards referral steps to either be confirmed or
      discounted as cases. Accurate surveillance thus relies not only on the
      performance of diagnostic technologies but also on referral support structures
      and patient decisions. This study explored why some RDT-positive suspects failed
      to complete the diagnostic referral process in West Nile, Uganda. METHODS:
      Between August 2013 and June 2015, 85% (295/346) people who screened RDT-positive
      were examined by microscopy at least once; 10 cases were detected. We interviewed
      20 RDT-positive suspects who had not completed referral (16 who had not presented
      for their first microscopy examination, and 4 who had not returned for a second
      to dismiss them as cases after receiving discordant [RDT-positive, but microscopy
      negative results]). Interviews were analysed thematically to examine experiences
      of each step of the referral process. RESULTS: Poor provider communication about
      HAT RDT results helped explain non-completion of referrals in our sample. Most
      patients were unaware they were tested for HAT until receiving results, and some
      did not know they had screened positive. While HAT testing and treatment is free,
      anticipated costs for transportation and ancillary health services fees deterred
      many. Most expected a positive RDT result would lead to HAT treatment. RDT
      results that failed to provide a definitive diagnosis without further testing led
      some to question the expertise of health workers. For the four individuals who
      missed their second examination, complying with repeat referral requests was less
      attractive when no alternative diagnostic advice or treatment was given.
      CONCLUSIONS: An RDT-based surveillance strategy that relies on referral through
      all levels of the health system is inevitably subject to its limitations. In
      Uganda, a key structural weakness was poor provider communication about the
      possibility of discordant HAT test results, which is the most common outcome for
      serological RDT suspects in a HAT elimination programme. Patient misunderstanding
      of referral rationale risks harming trust in the whole system and should be
      addressed in elimination programmes.

PMID- 30119703
TI  - Tuberculous sacroiliitis with secondary psoas abscess in an older patient: a case
      report.
AB  - BACKGROUND: Tuberculosis is the leading infectious cause of death worldwide.
      Among native Swiss people, tuberculosis is more common in older people than in
      younger people. Approximately 25-30% of reported cases of tuberculosis are purely
      extrapulmonary; skeletal tuberculosis is reported in 3-5% of cases. The purpose
      of this case report is to draw attention to the diagnostic challenge of
      tuberculous sacroiliitis with secondary psoas abscess, as this clinical picture
      is very rare. CASE PRESENTATION: A magnetic resonance imaging scan of an 85-year
      old (Swiss-German) Caucasian woman with chronic left-sided hip pain and
      limitation of hip joint movement showed a progressive destruction of her
      sacroiliac joint and a large collection in her left iliopsoas muscle. Drainage of
      the abscess revealed pus; a polymerase chain reaction assay was positive for
      Mycobacterium tuberculosis complex. Tuberculous sacroiliitis with secondary
      iliopsoas abscess was diagnosed 9 months after the start of the symptoms.
      Combination treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol
      was started. CONCLUSIONS: Sacroiliitis with secondary psoas abscess is an unusual
      cause of hip pain and is likely to be overlooked since joint pain of the lower
      extremity and lumbar pain are some of the most common complaints in older
      individuals. A high level of suspicion and invasive diagnostic procedures are
      needed for timely diagnosis of tuberculous sacroiliitis not only in
      immunocompromised patients living in or originating from endemic areas.

PMID- 30119702
TI  - Identification of key genes and pathways involved in response to pain in goat and
      sheep by transcriptome sequencing.
AB  - PURPOSE: This aim of this study was to investigate the key genes and pathways
      involved in the response to pain in goat and sheep by transcriptome sequencing.
      METHODS: Chronic pain was induced with the injection of the complete Freund's
      adjuvant (CFA) in sheep and goats. The animals were divided into four groups: CFA
      treated sheep, control sheep, CFA-treated goat, and control goat groups (n = 3 in
      each group). The dorsal root ganglions of these animals were isolated and used
      for the construction of a cDNA library and transcriptome sequencing.
      Differentially expressed genes (DEGs) were identified in CFA-induced sheep and
      goats and gene ontology (GO) enrichment analysis was performed. RESULTS: In
      total, 1748 and 2441 DEGs were identified in CFA-treated goat and sheep,
      respectively. The DEGs identified in CFA-treated goats, such as C-C motif
      chemokine ligand 27 (CCL27), glutamate receptor 2 (GRIA2), and sodium voltage
      gated channel alpha subunit 3 (SCN3A), were mainly enriched in GO functions
      associated with N-methyl-D-aspartate (NMDA) receptor, inflammatory response, and
      immune response. The DEGs identified in CFA-treated sheep, such as gamma
      aminobutyric acid (GABA)-related DEGs (gamma-aminobutyric acid type A receptor
      gamma 3 subunit [GABRG3], GABRB2, and GABRB1), SCN9A, and transient receptor
      potential cation channel subfamily V member 1 (TRPV1), were mainly enriched in GO
      functions related to neuroactive ligand-receptor interaction, NMDA receptor, and
      defense response. CONCLUSIONS: Our data indicate that NMDA receptor, inflammatory
      response, and immune response as well as key DEGs such as CCL27, GRIA2, and SCN3A
      may regulate the process of pain response during chronic pain in goats.
      Neuroactive ligand-receptor interaction and NMDA receptor as well as GABA-related
      DEGs, SCN9A, and TRPV1 may modulate the process of response to pain in sheep.
      These DEGs may serve as drug targets for preventing chronic pain.

PMID- 30119706
TI  - What does ICD-11 mean for child health professionals?

PMID- 30119705
TI  - Recurrent hypoglycemia secondary to metformin toxicity in the absence of co
      ingestions: a case report.
AB  - BACKGROUND: Metformin toxicity is well known to cause lactic acidosis. Multiple
      cases of hypoglycemia due to isolated metformin overdose have been reported.
      Increased glucose consumption secondary to anaerobic metabolism has been reported
      as a possible explanation. CASE PRESENTATION: A 23-year-old Arabic woman took 30
      g of metformin. In the emergency department, 4 hours after of the event, she was
      fatigued but vitally stable. During her hospitalization, she had severe lactic
      acidosis, hypotension corrected with fluid boluses and vasopressors, and multiple
      episodes of hypoglycemia (6.3 mg/dL, 38 mg/dL, and 42 mg/dL), requiring multiple
      50% dextrose-water boluses. The three hypoglycemic episodes occurred coincident
      with severe lactic acidosis. She improved after 24 hours of continuous renal
      replacement therapy. CONCLUSIONS: Hypoglycemia can be induced by metformin
      toxicity in the absence of co-ingestants. A possible explanation of metformin
      induced hypoglycemia is increased glucose consumption due to anaerobic
      metabolism, decreased oral intake, decreased liver glucose production, and
      decreased glucose absorption.

PMID- 30119704
TI  - How group singing facilitates recovery from the symptoms of postnatal depression:
      a comparative qualitative study.
AB  - BACKGROUND: Previous research has demonstrated that making music can enhance
      positive emotions as well as support positive psychological functioning. However,
      studies tend to be limited by lack of comparison with other psychosocial
      interventions. This study builds on a three-arm randomised controlled trial (RCT)
      that demonstrated that group singing for mothers and babies, but not group
      creative play, can lead to faster recovery from moderate-severe symptoms of
      postnatal depression than usual care. The aim was to elucidate the mechanisms of
      the group singing intervention in order to account for its recovery properties.
      METHODS: Qualitative research was conducted with 54 mothers who had experienced
      symptoms of postnatal depression. Mothers completed a 10-week programme of either
      group singing or group creative play as part of the wider RCT study. Data were
      collected via a series of 10 semi-structured focus groups conducted at the end of
      each 10-week programme. These were designed to elicit subjective and constructed
      experiences of the singing and play interventions and were analysed inductively
      for emergent themes. RESULTS: Five distinctive features of the group singing
      emerged: (i) providing an authentic, social and multicultural creative
      experience, (ii) ability to calm babies; (iii) providing immersive 'me time' for
      mothers; (iv) facilitating a sense of achievement and identity; (v) enhancing
      mother-infant bond. CONCLUSIONS: Community group singing interventions may reduce
      symptoms of postnatal depression through facilitating a functional emotional
      response rooted in the needs of new motherhood. These features are of relevance
      to others seeking to implement creative interventions for maternal mental health.
      TRIAL REGISTRATION: NCT02526407 . Registered 18 August 2015.

PMID- 30119708
TI  - The rise and rise of angiogenic biomarkers in the third trimester of pregnancy.

PMID- 30119707
TI  - The real impact of pneumococcal conjugate vaccines.

PMID- 30119709
TI  - Natural history data for childhood neurodegenerative disease.

PMID- 30119710
TI  - Psychotic episodes: markers of an eating disorder?

PMID- 30119711
TI  - Bronchopulmonary dysplasia: what's new on the horizon?

PMID- 30119712
TI  - Suicidal behaviour among children and adolescents in China.

PMID- 30119713
TI  - Global child and adolescent health: a call for papers.

PMID- 30119714
TI  - Putting the child into the children's hospital.

PMID- 30119715
TI  - Effectiveness of 13-valent pneumococcal conjugate vaccination for protection
      against acute otitis media caused by Streptococcus pneumoniae in healthy young
      children: a prospective observational study.
AB  - BACKGROUND: With wide use of the seven-valent pneumococcal conjugate vaccine
      (PCV7) for protection against acute otitis media caused by Streptococcus
      pneumoniae serotypes included in the vaccine, efficacy testing for the 13-valent
      vaccine (PCV13) was not feasible. We aimed to assess the effectiveness of PCV13
      in preventing acute otitis media caused by the six serotypes in PCV13 that were
      not in PCV7. METHODS: We did a longitudinal observational study in healthy
      children seen as outpatients in a private paediatric practice in Rochester, NY,
      USA. Children aged up to 30 months who had received the full primary series of
      PCV13 with other recommended vaccines were eligible to participate and were
      followed up to age 30-36 months to identify episodes of acute otitis media,
      during which we collected middle-ear fluid (MEF) by tympanocentesis. We assessed
      MEF for the serotypes common to PCV7 and PCV13 (4, 6B, 9V, 14, 18C, 19F, and 23F)
      and the six additional serotypes specific to PCV13 (1, 3, 5, 6A, 7F, and 19A). As
      controls, we included children enrolled in a longitudinal study in the study
      centre from Oct 1, 2007, to Sept 30, 2009, who had been vaccinated with PCV7, had
      MEF prospectively collected at the onset of acute otitis media, and been followed
      up until age 30 months. The primary outcome was the effectiveness of PCV13 to
      prevent acute otitis media caused by pneumococci expressing the six capsular
      serotypes not included in PCV7 (1, 3, 5, 6A, 7F, and 19A). This study is
      registered with ClinicalTrials.gov, number NCT01199016. FINDINGS: From Sept 28,
      2010, to Sept 30, 2013, we enrolled 239 children (123 [51%] boys and 116 [49%]
      girls; median age 6.3 months [IQR 6.1-8.6]) in the PCV13 cohort, and 162
      completed the study. Of 348 children (184 [53%] boys and 164 [47%] girls; 6.5
      months [6.1-9.1]) included in the PCV7 cohort, 248 completed follow-up. 223 MEF
      samples were obtained at onset of acute otitis media from 90 children in the
      PCV13 cohort. 53 (24%) of 223 samples were culture positive for S pneumoniae,
      compared with 89 (31%) of 284 samples in the PCV7 cohort (p=0.06). Four (8%) of
      53 samples in the PCV13 cohort contained pneumococci expressing one of the
      additional PCV13 capsular serotypes, compared with 46 (52%) of 89 samples in the
      PCV7 cohort, giving a relative reduction of 86% (95% CI 61-94, p=0.0010). The
      greatest reduction in MEF samples was in serotype 19A (two [4%] in the PCV13
      cohort vs 46 [52%] in the PCV7 cohort; relative reduction 91% [58-97, p=0.0010]).
      INTERPRETATION: PCV13 prevents acute otitis media caused by S pneumoniae
      expressing serotypes included in the vaccine. FUNDING: Pfizer.

PMID- 30119716
TI  - Screening for fetal growth restriction using ultrasound and the sFLT1/PlGF ratio
      in nulliparous women: a prospective cohort study.
AB  - BACKGROUND: Fetal growth restriction is a major determinant of perinatal
      morbidity and mortality. This condition has no gold standard definition, but a
      widely used proxy is delivery of a small for gestational age infant (<10th
      percentile) combined with an adverse pregnancy outcome. Effective screening for
      fetal growth restriction is an area of unmet clinical need. We aimed to determine
      the diagnostic effectiveness of a combination of ultrasonic fetal biometry and
      measurement of the ratio of soluble fms-like tyrosine kinase receptor 1 (sFLT1)
      to placental growth factor (PlGF) in predicting adverse pregnancy outcomes
      associated with delivery of a small for gestational age infant. METHODS: In this
      prospective cohort study, using serial antenatal blood sampling and blinded
      ultrasound scans, we investigated the association between the combination of an
      elevated sFLT1/PlGF ratio (>85th percentile) and ultrasonically suspected small
      for gestational age (<10th percentile) at both 28 and 36 weeks of gestational
      age. The outcome following the 28 week measurement was preterm delivery of a
      small for gestational age infant. The outcome following the 36 week measurement
      was subsequent delivery of a small for gestational infant associated with
      maternal pre-eclampsia or perinatal morbidity or mortality. All definitions of
      exposure and outcome were predefined before we did our data analysis. FINDINGS:
      Between Jan 14, 2008, and July 31, 2012, we recruited 4512 nulliparous women.
      4098 women (91%) had a sFLT1/PlGF ratio measurement and estimated fetal weight at
      28 or 36 weeks of gestational age, and outcome data available. 3981 women were
      analysed for 28 weeks of gestational age measurements and 3747 women were
      analysed for 36 weeks of gestational age measurements. At 28 weeks, 47 (1%) of
      3981 women had the combination of ultrasonic small for gestational age and an
      elevated sFLT1/PlGF ratio. The positive likelihood ratio for preterm delivery of
      a small for gestational age infant associated with this combination was 41.1 (95%
      CI 23.0-73.6), the sensitivity was 38.5% (21.1-59.3), the specificity was 99.1%
      (98.7-99.3), and the positive predictive value was 21.3% (11.6-35.8). At 36
      weeks, 102 (3%) of 3747 women had the combination of ultrasonic small for
      gestational age and an elevated sFLT1/PlGF ratio. The positive likelihood ratio
      for delivery of a small for gestational age infant associated with maternal pre
      eclampsia or perinatal morbidity or mortality was 17.5 (95% CI 11.8-25.9), the
      sensitivity was 37.9% (26.1-51.4), the specificity was 97.8% (97.3-98.3), and the
      positive predictive value was 21.6% (14.5-30.8). The positive likelihood ratios
      at both gestational ages were higher than previously described definitions of
      suspected fetal growth restriction using purely ultrasonic assessment.
      INTERPRETATION: The combination of ultrasonically suspected small for gestational
      age plus an elevated sFLT1/PlGF ratio in unselected nulliparous women identified
      a relatively small proportion of women who have high absolute risks of clinically
      important adverse outcomes. Screening and intervention based on this approach
      could result in net benefit and this could be an appropriate subject for a
      randomised controlled trial. FUNDING: NIHR Cambridge Comprehensive Biomedical
      Research Centre, Medical Research Council, and Stillbirth and neonatal death
      society (Sands).

PMID- 30119717
TI  - Disease characteristics and progression in patients with late-infantile neuronal
      ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study.
AB  - BACKGROUND: Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease,
      characterised by rapid psychomotor decline and epilepsy, is caused by deficiency
      of the lysosomal enzyme tripeptidyl peptidase 1. We aimed to analyse the
      characteristics and rate of progression of CLN2 disease in an international
      cohort of patients. METHODS: We did an observational cohort study using data from
      two independent, international datasets of patients with untreated genotypically
      confirmed CLN2 disease: the DEM-CHILD dataset (n=74) and the Weill Cornell
      Medical College (WCMC) dataset (n=66). Both datasets included quantitative rating
      assessments with disease-specific clinical domain scores, and disease course was
      measured longitudinally in 67 patients in the DEM-CHILD cohort. We analysed these
      data to determine age of disease onset and diagnosis, as well as disease
      progression-measured by the rate of decline in motor and language summary scores
      (on a scale of 0-6 points)-and time from first symptom to death. FINDINGS: In the
      combined DEM-CHILD and WCMC dataset, median age was 35.0 months (IQR 24.0-38.5)
      at first clinical symptom, 37.0 months (IQR 35.0 -42.0) at first seizure, and
      54.0 months (IQR 47.5-60.0) at diagnosis. Of 74 patients in the DEM-CHILD
      dataset, the most common first symptoms of disease were seizures (52 [70%]),
      language difficulty (42 [57%]), motor difficulty (30 [41%]), behavioural
      abnormality (12 [16%]), and dementia (seven [9%]). Among the 41 patients in the
      DEM-CHILD dataset for whom longitudinal assessments spanning the entire disease
      course were available, a rapid annual decline of 1.81 score units (95% CI 1.50
      2.12) was seen in motor-language summary scores from normal (score of 6) to no
      function (score of 0), which occurred over approximately 30 months. Among 53
      patients in the DEM-CHILD cohort with available data, the median time between
      onset of first disease symptom and death was 7.8 years (SE 0.9) years.
      INTERPRETATION: In view of its natural history, late-infantile CLN2 disease
      should be considered in young children with delayed language acquisition and new
      onset of seizures. CLN2 disease has a largely predictable time course with regard
      to the loss of language and motor function, and these data might serve as
      historical controls for the assessment of current and future therapies. FUNDING:
      EU Seventh Framework Program, German Ministry of Education and Research, EU
      Horizon2020 Program, National Institutes of Health, Nathan's Battle Foundation,
      Cures Within Reach Foundation, Noah's Hope Foundation, Hope4Bridget Foundation.

PMID- 30119719
TI  - Genetic therapies for inherited neuromuscular disorders.
AB  - Inherited neuromuscular disorders encompass a broad group of genetic conditions,
      and the discovery of these underlying genes has expanded greatly in the past
      three decades. The discovery of such genes has enabled more precise diagnosis of
      these disorders and the development of specific therapeutic approaches that
      target the genetic basis and pathophysiological pathways. Such translational
      research has led to the approval of two genetic therapies by the US Food and Drug
      Administration: eteplirsen for Duchenne muscular dystrophy and nusinersen for
      spinal muscular atrophy, which are both antisense oligonucleotides that modify
      pre-mRNA splicing. In this Review we aim to discuss new genetic therapies and
      ongoing clinical trials for Duchenne muscular dystrophy, spinal muscular atrophy,
      and other less common childhood neuromuscular disorders.

PMID- 30119718
TI  - Longitudinal associations between psychotic experiences and disordered eating
      behaviours in adolescence: a UK population-based study.
AB  - BACKGROUND: Psychotic experiences might represent non-specific markers of poor
      mental health in adolescence. However, only a few predominantly cross-sectional
      studies have tested their association with disordered eating behaviours in
      adolescent and adult populations. The aim of this study was to explore the
      association between psychotic experiences at age 13 years, and disordered eating
      behaviours and body-mass index (BMI) at age 18 years. METHODS: We used data from
      the Avon Longitudinal Study of Parents and Children, a longitudinal birth cohort
      based in Avon (England, UK) including mothers with an expected delivery date
      between April 1, 1991, and Dec 31, 1992, and their children. Psychotic
      experiences (such as delusions and hallucinations) and BMI were measured at
      clinical assessments when children were nearly aged 13 years, and data on
      disordered eating behaviours (ie, presence of binge eating, purging, fasting, or
      excessive exercise for weight loss; any of these behaviours [included to increase
      statistical power]; and number of behaviours [included to investigate severity])
      were obtained via a postal questionnaire that used adapted questions from the
      Youth Risk Behaviour Surveillance System questionnaire at approximately age 18
      years. For each outcome, we ran a univariable model and four multivariable models
      (logistic, linear [for BMI], or negative binomial [for the number of behaviours]
      regression), progressively adjusting for child and maternal sociodemographic,
      physical, and mental health characteristics (including child's sex, and maternal
      age, marital status, and highest academic qualification); autistic traits at age
      7 years (measured with the Social and Communication Disorder Checklist); baseline
      BMI at age 13 years, and depressive symptoms at baseline (ie, at age 13 years
      when psychotic experiences were measured: childs' symptoms measured with the
      Moods and feelings Questionnaire, and maternal symptoms measured at 32 weeks'
      gestation with the Edinburgh Postnatal Depression Scale). We imputed missing
      outcome and covariate data. FINDINGS: Our sample included 6361 children, of whom
      734 (12%) reported psychotic experiences at age 13 years. In univariable models,
      psychotic experiences were associated with greater odds of reporting any
      disordered eating behaviours (odds ratio [OR] 1.92, 95% CI 1.46-2.52; p<0.0001),
      and more severe symptoms (as measured by the number of disordered eating
      behaviours: 0.58, 0.32-0.84; p<0.0001) at age 18 years. These associations were
      slightly attenuated by adjustment for maternal and child characteristics (any
      disordered eating behaviours OR 1.82, 95% CI 1.35-2.44, p<0.0001; number of
      disordered eating behaviours 0.49, 95% CI 0.23-0.75, p<0.00001), autistic traits
      at age 7 years (any disordered eating behaviours OR 1.80, 95% CI 1.34-2.41,
      p<0.0001; number of disordered eating behaviours 0.48, 95% CI 0.22-0.74,
      p<0.00001), and BMI (any disordered-eating behaviours OR 1.83, 95% CI 1.36-2.46,
      p<0.0001; number of disordered-eating behaviours 0.32, 95% CI 0.06-0.57,
      p<0.00001) Adjusting for baseline depressive symptoms attenuated, but not
      removed, these associations (any disordered eating OR 1.50, 95% CI 1.10-2.03,
      p=0.010; more severe symptoms 0.32, 0.06-0.57, p=0.017). Psychotic experiences
      were also associated with greater binge eating, purging, and fasting behaviours,
      although some associations weakened after controlling for depressive symptoms. We
      noted no associations between psychotic experiences and excessive exercise or BMI
      in any of the models. INTERPRETATION: Our findings suggested that psychotic
      experiences are markers of increased risk for several disordered eating
      behaviours in late adolescence, possibly by indicating more severe
      psychopathology in early adolescence. More research investigating shared risk
      factors for psychotic experiences and eating disorders is warranted to elucidate
      shared and specific causal pathways. FUNDING: Wellcome Trust, the Royal Society,
      University College London Hospitals National Institute for Health Research
      Biomedical Research Centre, UK Medical Research Council, and the University of
      Bristol.

PMID- 30119721
TI  - Challenges to paediatric cardiac services in South Africa.

PMID- 30119720
TI  - Neonatal hyperbilirubinaemia: a global perspective.
AB  - Hyperbilirubinaemia, presenting as jaundice, is a ubiquitous and frequently
      benign condition in newborn babies but is a leading cause of hospitalisation in
      the first week of life. In some infants jaundice can become severe, progressing
      to acute bilirubin encephalopathy and kernicterus with a substantial risk of
      neonatal mortality and long-term neurodevelopmental impairments. Severe
      hyperbilirubinaemia and its sequelae continue to occur in industrialised
      countries with functioning medical systems and a disproportionately high burden
      also persists in low-income and middle-income countries due primarily to delays
      in delivering effective treatments that are routinely available in high-income
      countries. In this Review we summarise up-to-date evidence on the epidemiology of
      neonatal jaundice including its global burden based on estimates of its
      prevalence, and both fatal and non-fatal health outcomes. We also discuss the
      management of severe hyperbilirubinaemia including the prevention of kernicterus,
      and highlight future directions for research.

PMID- 30119722
TI  - Normalising menstruation, empowering girls: the situation in Sri Lanka.

PMID- 30119723
TI  - Dismantling menstrual taboos to overcome gender inequality.

PMID- 30119724
TI  - Inclusion of menstrual health in sexual and reproductive health and rights.

PMID- 30119726
TI  - Affinity-Based Separation Methods for the Study of Biological Interactions.

PMID- 30119725
TI  - Inclusion of menstrual health in sexual and reproductive health and rights -
      Authors' reply.

PMID- 30119727
TI  - The use of infrared spectroscopic techniques to characterize nanomaterials and
      nanostructures: A review.
AB  - Recent advances in nanotechnology have opened a lot of new possibilities for
      nanomaterials application in wide variety of industrial, pharmaceutical,
      medicinal and environmental applications. This review aims to description of
      various Fourier Transform Infrared (FTIR)-based spectroscopic techniques suitable
      to characterize (i) different types of nanomaterials and (ii) various macroscopic
      samples at their nanoscale. In the introductory section, nanomaterials are
      classified according to their crucial properties, i.e. chemical composition, size
      and surface morphology. Application of traditional FTIR techniques, such as
      Attenuated Total Reflection (ATR), Diffuse Reflection (DRIFT) and infrared micro
      (spectro)scopy, for characterization of nanomaterials and nanostructures is
      compared with novel optical nanoscopic techniques derived from scanning probe
      microscopy which enable to overcome the diffraction limit and to characterize
      nanomaterials at molecular scale.

PMID- 30119728
TI  - A strategy for the metabolomics-based screening of active constituents and
      quality consistency control for natural medicinal substance toad venom.
AB  - Natural medicinal substances (NMS) have great inconsistency due to chemical
      variability, seriously limiting their development as therapeutics. Here, we chose
      toad venom with anti-tumor activities as a model and developed a pipeline of
      metabolomics-based screening and quality consistency control (MSQCC) as one
      potential solution to this long-standing problem. Our study firstly exemplified
      the power of the co-correlation screen of metabolomic and biological profiles of
      180 fractions prepared from natural heterogeneous venom samples, to identify a
      series of bufadinolides as quality control markers for cancer cell inhibition.
      The next quantitative monitoring of these markers revealed great batch-to-batch
      variation of toad venoms. Finally, we developed a marker-based blending program
      (Markers-NMBT) to normalize heterogeneity of NMS. It created the blends for the
      conversion of the unqualified venoms with high variation in the contents of
      bufadienolides, into qualified products consistent with the reference. Thus, this
      work provides a strategy for rapid, large-scale discovery, quantification and
      application of quality control markers to ensure batch-to-batch consistency, and
      can be a crucial technology in the development of modern NMS preparations.

PMID- 30119729
TI  - Spatio-temporal profiling of abscisic acid, indoleacetic acid and jasmonic acid
      in single rice seed during seed germination.
AB  - Abscisic acid (ABA), indoleacetic acid (IAA) and jasmonic acid (JA) are plant
      hormones that were reported to play indispensable roles during seed germination.
      However, the interactions between these plant hormones during rice seed
      germination have still not been explored clearly. A sensitive method for
      determination of these plant hormones would be beneficial for the exploration of
      such interactions. Herein, we present a liquid chromatography coupled with mass
      spectrometry (LC-MS) method for the quantification of ABA, IAA and JA in a single
      tissue of rice seed to investigate the spatio-temporal distribution of these
      plant hormones during rice seed germination. To this end, an in silico strategy
      was developed in order to select a derivatization reagent with an ideal
      sensitivity of MS detection. This strategy was confirmed with experimental
      studies on three reagents N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC),
      N,N-dimethylethylenediamine (DMED), and N-(acridin-9-yl)-2-bromoacetamide (AYBA)
      and their formic acid derivatives. Our results from the in silico and LC-MS
      experiments show that AYBA is a good derivatization reagent for ABA, IAA and JA
      due to its reasonable ionization efficiency in electrospray ionization mass
      spectrometry (ESI-MS) and excellent hydrophobicity. Finally, a sensitive LC-MS
      method upon AYBA was established for the determination of ABA, IAA and JA in
      germinated seeds. Good linearities for ABA, IAA, and JA were obtained with
      correlation coefficients greater than 0.99. The limits of detection (LODs) were
      in the range of 0.14-0.16 pg mL-1. The method exhibits good precisions with RSD
      1.5%-13.8% (intra-day) and 1.2%-7.3% (inter-day) and acceptable recoveries (88.6%
      102.9%, n = 6). Finally, the method was successfully employed in the spatio
      temporal profiling of ABA, IAA and JA in a single tissue of rice seed during rice
      seed germination.

PMID- 30119730
TI  - Forced dried droplet method for MALDI sample preparation.
AB  - A forced dried droplet method (FDD) is developed to overcome the drawbacks of the
      conventional dried-droplet (DD) method for matrix assisted laser
      desorption/ionization (MALDI) sample preparation. The crystals produced by the DD
      method are heterogeneous and irregularly distributed, and thus many methods have
      tried to solve the problems. However, most of them spend more time or need
      additional instruments to generate homogeneous microcrystals. The FDD sample
      preparation method can produce uniform microcrystals with homogeneous size
      distribution in few minutes without additional instruments. Stirring the sample
      spot solution (an agitation process) with a pipette tip can change the crystal
      size distribution which is observed by the microscope. Mass spectrometric
      analysis shows that the smaller the crystal size is, the better the ion signal
      intensity is. The formation of microcrystals can be explained with the effective
      rate of secondary nucleation. The relative standard deviation (RSD) of the FDD
      method is ~16% which is comparable to the two-layer (TL) method and is better
      than the DD method.

PMID- 30119731
TI  - A class-specific artificial receptor-based on molecularly imprinted polymer
      coated quantum dot centers for the detection of signaling molecules, N-acyl
      homoserine lactones present in gram-negative bacteria.
AB  - Herein, a novel class-specific artificial receptor-based on molecularly imprinted
      polymer (MIP)-coated quantum dots (QDs@MIP) was synthesized, characterized, and
      used for the detection and quantification of the bacterial quorum signaling
      molecules N-acyl-homoserine lactones (AHLs), a class of autoinducers from Gram
      negative bacteria. The QDs@MIP was prepared by surface imprinting technique under
      controlled conditions using CdSe/ZnS QDs as the signal transducing material. The
      synthesis of the QDs@MIP was characterized by transmission electron microscopy,
      scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray
      diffraction analysis, and fluorescence spectroscopy. After template elution, the
      obtained cavities sensitively and selectively recognized the target AHLs of
      interest. The fluorescence intensity of the QDs@MIP was significantly quenched
      compared to the control non-imprinted polymer (QDs@NIP) upon exposure to
      different AHL concentrations. It also had a good linearity in the range from 2 to
      18 nM along with a detection limit of 0.66, 0.54, 0.88, 0.72 and 0.68 nM for
      DMHF, C4-HSL, C6-HSL, C8-HSL and N-3oxo-C6-HSL, respectively. Most interestingly,
      the proposed sensor exhibited high sensitivity, good stability and fast response
      (30 s) towards the target molecules due to successful formation of surface
      imprints. The practicability of the developed sensor in real samples was further
      confirmed through the analysis of bacterial supernatant samples with satisfactory
      recoveries ranging from 89 to 103%. According to these results, the as-prepared
      QDs@MIP can be used as a new potential supporting technique for the rapid and
      real-time detection of bacterial pathogens in food safety and healthcare
      facilities.

PMID- 30119733
TI  - Potential of nanoparticle-based hybrid monoliths as sorbents in microextraction
      techniques.
AB  - This article reviews the synthesis and uses of nanoparticle-based hybrid
      monoliths in microextraction techniques. Synthesizing monolithic solids
      containing nanoparticles allows the advantages of the two sorbent phases to be
      synergistically combined. The resulting hybrid material exhibits outstanding
      capabilities for isolating the target compounds from the samples. In addition to
      conventional in-cartridge solid-phase extraction, the monoliths can be easily
      adapted for use in most of the usual formats of micro-solid phase extraction
      including capillaries, pipette tips, spin columns, microfluidic chips and stirred
      units. The most salient uses devised so far are described and critically
      discussed in this article, which deals with both silica and organic monolithic
      solids modified with nanostructured materials including carbonaceous and metal or
      metal oxide nanoparticles.

PMID- 30119732
TI  - New detection method for nucleoside triphosphates based on carbon dots: The
      distance-dependent singlet oxygen trapping.
AB  - The distance-dependent based sensing mechanism, such as fluorescence resonance
      energy transfer (FRET) and surface plasmon resonance (SPR) absorption of gold
      nanoparticles, has been used widely in visual detection. In this work, we report
      another distance-dependent detection method for nucleoside triphosphates (NTPs)
      based on carbon dots (CDs) (1O2 donor) and 9, 10-diphenylanthracene-2-boronic
      acid (DABA, 1O2 acceptor). The CDs can generate singlet oxygen (1O2) which allows
      diffusion within 200 nm. Thus, the distance between CDs and DABA decreased
      through binding of NTPs (<200 nm), leading to absorption changes of DABA under
      light irradiation due to 1O2 trapping. This sensing system (CDs@DABA) has high
      selectivity for the detection of NTPs due to the double molecular recognition and
      a linear response in the 0-80 MUM concentration range was accomplished with the
      detection limit as low as 4.35 MUM.

PMID- 30119734
TI  - Fluorescence turn on detection of bilirubin using Fe (III) modulated BSA
      stabilized copper nanocluster; A mechanistic perception.
AB  - Hyperbilirubinemia is the condition when bilirubin exceeds normal concentration
      in body (19.80 mg/mL in newborns and 1.19 * 10-2 mg/mL in adults). Bilirubin
      encephalopathy in newborns may cause irreversible neurological disorders. Current
      methods for detection of bilirubin suffer from compromising accuracy. In the
      present work, bovine serum albumin stabilized copper nanocluster (BSA-CuNCs) was
      synthesized via a one pot microwave assisted method as a turn on detector for
      bilirubin. The synthesized BSA-CuNCs having size less than 4 nm, exhibited bright
      blue emission at 405 nm. Interestingly, no observable change in fluorescence
      emission was noticed over a wide pH range (1-11) or at high ionic conditions.
      However, the interaction of Fe3+ with BSA-CuNCs induces quenching of
      fluorescence. Moreover, the fluorescence can be regained by the addition of
      bilirubin over other possible coexisting biomolecules. A good linearity was
      observed for BSA-CuNCs based turn on probe with a Limit of Detection (LoD) 6.62
      nM. Furthermore, real sample analyses were carried out with human serum and urine
      which showed good recovery percentage.

PMID- 30119735
TI  - Novel quartz crystal microbalance immunodetection of aflatoxin B1 coupling cargo
      encapsulated liposome with indicator-triggered displacement assay.
AB  - A simple and sensitive quartz crystal microbalance (QCM) immunosensing platform
      was designed for the high-efficient detection of aflatoxin B1 (AFB1) in
      foodstuff. Initially, phenoxy-derived dextran molecule was immobilized on the
      surface of QCM gold substrate by using thiolated beta-cyclodextrin based on the
      supramolecular host-guest chemistry between phenoxy group and cyclodextrin. Then,
      AFB1-bovine serum albumin (AFB1-BSA)-conjugated concanavalin A (Con A) was
      assembled onto the QCM probe through the dextran-Con A interaction. Glucose
      loaded nanoliposome, labeled with monocolonal anti-AFB1 antibody, was used for
      the amplification of QCM signal. Upon target AFB1 introduction, the analyte
      competed with the immobilized AFB1-BSA on the probe for the labeled anti-AFB1
      antibody on the nanoliposome. Based on specific antigen-antibody reaction, the
      amount of the conjugated nanoliposomes on the QCM probe gradually decreased with
      the increment of target AFB1 in the sample. Upon injection of Triton X-100 in the
      detection cell, the carried nanoliposome was lysed to release the encapsulated
      glucose molecules. Thanks to the stronger affinity of Con A toward glucose than
      that of dextran, AFB1-BSA-labeled Con A was displaced from the QCM probe,
      resulting in the change of the local frequency. Under the optimum conditions, the
      shift of the functionalized QCM immunosensing interface in the frequency shift
      was proportional to the concentration of target AFB1 within a dynamic range from
      1.0 ng kg-1 to 10 MUg kg-1 at a low detection limit of 0.83 ng kg-1. In addition,
      the acceptable assayed results on precision, reproducibility, specificity and
      method accuracy for the analysis of real samples were also acquired. Importantly,
      our strategy can provide a signal-on competitive immunoassay for the detection of
      small molecules, e.g., mycotoxins and biotoxins, thereby representing a versatile
      sensing schemes by controlling the corresponding antibody or hapten in the
      analysis of food safety.

PMID- 30119736
TI  - A turn-on fluorescence probe based on aggregation-induced emission for leucine
      aminopeptidase in living cells and tumor tissue.
AB  - Abnormally-expressed leucine aminopeptidase (LAP) is associated with diverse
      physiological and pathological disorders; hence developing a highly selective and
      sensitive detection system for LAP is of great significance. Herein, a
      fluorescent light-up system with aggregation-induced emission (AIE)
      characteristic, (DPA-TPE-Leu) has been developed for detecting LAP, in which the
      recognition unit l-leucine amide group also acts as the hydrophilic moiety. Upon
      LAP-triggered enzymatic reaction, l-leucine amide moiety is cleaved from the
      probe molecule, resulting in the formation and aggregation of the hydrophobic
      reaction product (DPE-TPE-OH) with AIE effect and thus giving out the turn-on
      green fluorescence. The system features excellent photostability, large Stokes
      shift (194 nm), good water solubility, high sensitivity with the detection limit
      of 0.16 U L-1, favorable specificity and low cytotoxicity. It has been
      effectively utilized in fluorescent imaging of endogenous LAP in living cells,
      and also successfully applied for fluorescent imaging of HepG2 xenograft tumor.
      Such a fluorescent assay could provide a convenient and sensitive method for
      detecting LAP activity and might aid in the auxiliary diagnosis of hepatocellular
      carcinoma and related pathological analysis in biopsy.

PMID- 30119737
TI  - Determination of 226Ra at low levels in environmental, urine, and human bone
      samples and 223Ra in bone biopsy using alpha-spectrometry and metrological
      traceability to 229Th/225Ra or 226Ra.
AB  - 226Ra is a natural radioelement emitting alpha and gamma radiations. It can be
      highly concentrated in TENORM materials from the petroleum or fertilizer
      industries. In Switzerland, 226Ra is currently a radioactive inheritance problem
      from the watch industry. Furthermore, 223Ra is a radium isotope used in nuclear
      medicine to treat bone metastasis. There exist several methods to measure radium
      using alpha or gamma spectrometry or using 222Rn emanation technique. The
      limitations of these methods are due to the required detection limits and the
      nature of the samples. When using alpha spectrometry to reach very low detection
      limits, critical technical hitches often arise because of the difficulties in
      separating radium from barium, in removing organics eluted from the separating
      chromatography column, and in plating radium. Moreover, overall chemical recovery
      of radium is often not reproducible, depending on the studies. Here we propose a
      method that separates radium from other alkaline-earth cations using cation
      exchange chromatography and selective complex formation by EDTA and DCTA. Radium
      is completely free of the 229Th tracer and its daughter products, particularly
      225Ac. Organics from the column are removed in a further purification step so
      that radium can be plated with acceptable yields in a HCl/HNO3/ethanol solution.
      We successfully applied the method to soil, water, urine and human bone samples
      and further extended it to the determination of 223Ra in a bone biopsy, using
      226Ra as an internal tracer.

PMID- 30119738
TI  - Simultaneous determination of PUFA-derived pro-resolving metabolites and pathway
      markers using chiral chromatography and tandem mass spectrometry.
AB  - Lipid mediators play an important role as biological messengers involved in
      inflammatory processes. Deriving from different polyunsaturated fatty acids,
      endogenously built mediators featuring both pro- and anti-inflammatory properties
      as well as pro-resolving lipid mediators and their biological precursors have
      been investigated. A newly developed method using chiral chromatography-tandem
      mass spectrometry on human plasma has demonstrated its suitability for the
      simultaneous determination of prostaglandins, lipoxins, D-series derived
      resolvins as well as protectins, maresin 1, leukotriene B4 and several precursors
      of them in order to yield information about metabolic pathways. Due to the matrix
      complexity, a solid phase extraction method using an octadecyl-modified silica
      gel cartridge was carried out. The developed method allows the determination of
      34 analytes in 25 min showing enough selectivity as well as precision and
      accuracy (<=15% relative standard deviation, <=15% relative error) in the
      calibration range of 0.1-10 ng mL-1 or 0.2-20 ng mL-1 depending on the analytes.
      Stability of the analytes in plasma has been demonstrated for at least 3 h at
      room temperature, 72 h in the autosampler and 60 days in the freezer at -80 
      degrees C. This method has been validated and shown its suitability for the
      determination of all studied analytes in human plasma samples.

PMID- 30119739
TI  - Corrigendum to "A novel approach for electroanalytical determinations employing
      discharge of pseudocapacitor by electroactive species" [Analytica Chimica Acta
      1006 (2018) 1-9].
AB  - The purpose of this Corrigendum is to cite and comment on an important reference
      that brings some support to the ideas developed in this paper and should be
      chronologically inserted into the history of advances in this area.

PMID- 30119740
TI  - Corrigendum to "Intact metabolite profiling of mouse brain by probe electrospray
      ionization/triple quadrupole tandem mass spectrometry (PESI/MS/MS) and its
      potential use for local distribution analysis of the brain" [ACA 983 (2017) 160
      165].

PMID- 30119741
TI  - Chemometric approaches for document dating: Handling paper variability.
AB  - A non-destructive methodology based on Fourier Transformed Infrared Spectroscopy
      (FTIR) is proposed in this research to estimate the age of documents of different
      ages. Due the variability in the samples caused by their different chemical
      compositions, chemometric approaches were proposed to build one unique regression
      model able to determine the age of the paper regardless of its composition. PLS
      models were built employing Generalized Least Squares Weighting (GLSW) and
      Orthogonal Least Squares (OLS) filters to reduce the variability of samples from
      the same year. Afterwards, sparse PLS, which is an extension of the PLS model
      including a variable selection step, was applied to compare its performance with
      the preprocessing filters. All techniques proposed were compared to the initial
      PLS models, showing the potential of the chemometric approaches applied to FTIR
      data to estimate the age of unknown documents.

PMID- 30119742
TI  - Band target entropy minimization and target partial least squares for spectral
      recovery and quantitation.
AB  - The resolution and quantitation of pure spectra of minority components in
      measurements of chemical mixtures without prior knowledge of the mixture is a
      challenging problem. In this work, a combination of band target entropy
      minimization (BTEM) and target partial least squares (T-PLS) was used to obtain
      estimates for single pure component spectra and to calibrate those estimates in a
      true, one-at-a-time fashion. This approach allows for minor components to be
      targeted and their relative amounts estimated in the presence of other varying
      components in spectral data. The use of T-PLS estimation is an improvement to the
      BTEM method because it overcomes the need to identify all of the pure components
      prior to estimation. Estimated amounts from this combination were found to be
      similar to those obtained from a standard method, multivariate curve resolution
      alternating least squares (MCR-ALS), on a simple, three component mixture
      dataset. Studies from two experimental datasets demonstrate where the combination
      of BTEM and T-PLS was used to model the pure component spectra and to obtain
      concentration profiles of minor components, but MCR-ALS could not.

PMID- 30119743
TI  - NiO nanoparticles modified carbon paste electrode as a novel sulfasalazine
      sensor.
AB  - The sol-gel synthesized NiO nanoparticles were characterized and used for the
      modification of a carbon paste electrode (CPE) in electrocatalytic voltammetric
      determination of sulfasalazine. Calcination temperature of NiO had an important
      role on the peak current of the modified NiO-CPE and calcined NiO at 200  degrees
      C had the best and maximum peak current for the corresponding electrode. Jahn
      Teller and a Z-out effects for the singlet electrons in their 3dz2 orbital for
      calcined NiO at 200  degrees C relatively instable such electrons and hence they
      can easily participate in the electro-oxidation process. The electrochemical
      impedance spectroscopy (EIS) results confirmed that the modified CPE by calcined
      NiO at 200  degrees C has lower charge transfer resistance. In interaction
      effects study between the experimental variables by using the response surface
      methodology (RSM) approach, the optimized run included the 17.5% of NiO modifier,
      0.5 M NaOH, amplitude of 295 mV, step potential of 7 mV and frequency of 15 Hz. A
      calibration plot in the range of 0.009-1.6 MUM with limits of detection (LOD) and
      quantification (LOQ) of 0.002 and 0.006 MUM was obtained, respectively. The
      modified electrode showed good selectivity and applicability for SSZ
      determination in complex matrixes.

PMID- 30119745
TI  - Current pulse based ion-selective electrodes for chronopotentiometric
      determination of calcium in seawater.
AB  - Calcium is closely related to the oceanic biosphere and carbonate system.
      Potentiometry based on a calcium-selective electrode (Ca-ISE) represents a
      promising tool for detection of calcium ion activities in seawater. This
      technique, however, generally is limited by the low sensitivity for the inherent
      Nernstian response (i.e. ca 30 mV/dec). A current pulse based ion-selective
      electrode with enhanced sensitivity for chronopotentiometric measurements of
      calcium in seawater is proposed. The Ca2+-selective membrane containing
      lipophilic salt ETH 500 instead of traditional ion-exchanger is galvanostatically
      controlled. An applied constant cathodic current pulse can leads to the
      extraction of the calcium ions into the membrane to produce a chronopotential
      response, which shows a stable and reproducible super-Nernstian response in a
      narrow calcium activity range. The super-Nernstian region of the electrode
      depends on not only the the magnitude and duration of the applied current pulse
      but also the interfering ions. Under optimal conditions, the proposed Ca-ISE
      exhibits a super-Nernstian response between the calcium concentrations of 10-2.5
      10-1.5 M with a slope of ca 80 mV/dec. The current pulse based Ca-ISE has been
      applied to determination of calcium in seawater with satisfactory results.

PMID- 30119744
TI  - Morphology-dependent electrochemical sensing performance of metal (Ni, Co, Zn)
      organic frameworks.
AB  - To clarify the morphology effect of metal-organic frameworks (MOFs) on their
      electrochemistry as well as to explore their electrochemical applications, three
      MOFs with metal centers of nickel, cobalt, and zinc are synthesized. The used
      organic ligand is only 1,3,5-benzenetricarboxylic acid. Characterizations using
      Fourier Transform infrared spectroscopy, X-ray diffraction, scanning electron
      microscopy, and electrochemical techniques reveal that these MOFs possess similar
      bonding properties, crystalline structures and phase purity, but various
      morphology and electrochemical activities, including their own redox behavior,
      electrochemical response toward redox probes and analytes in solutions. As a case
      study of analytes, voltammetry of Ponceau 4R is investigated on three MOFs. Its
      sensitive and selective monitoring is further achieved on nickel MOFs with a
      linear range from 0.5 to 150 nM and a detection limit of 80 pM. Therefore, the
      morphology of MOFs determines electrochemistry of MOFs and their electrochemical
      sensing applications.

PMID- 30119746
TI  - Poly(glycine)/graphene oxide modified glassy carbon electrode: Preparation,
      characterization and simultaneous electrochemical determination of dopamine, uric
      acid, guanine and adenine.
AB  - A novel poly(glycine) (p-GLY)/graphene oxide (GO) composite based sensor (p
      GLY/GO) was successfully prepared on glassy carbon electrode by simple
      electropolymerization. Electrochemical responses of analytes on p-GLY/GO modified
      electrode were studied by cyclic voltammetry and differential pulse voltammetry.
      The results demonstrated that p-GLY/GO modified electrode showed a favorable
      application for the simultaneous determination of dopamine (DA), uric acid (UA),
      guanine (GU) and adenine (AD). Owing to the synergistic effect of p-GLY and GO,
      the oxidation peaks of four analytes separated well from each other, and the
      potential separations of oxidation peaks of DA-UA, UA-GU and GU-AD were large up
      to 170, 350 and 300 mV, respectively. As-prepared p-GLY/GO modified electrode
      offered wide linear responses for DA, UA, GU and AD over the ranges of 0.20-62,
      0.10-105, 0.15-48 and 0.090-103 MUM with detection limits of 0.011, 0.061, 0.026
      and 0.030 MUM (S/N = 3), respectively. Moreover, p-GLY/GO modified electrode
      presented favorable selectivity, stability and reproducibility, which was a
      promising candidate as an electrochemical sensor for the simultaneous
      determination of DA, UA, GU and AD.

PMID- 30119747
TI  - Direct immersion solid-phase microextraction analysis of multi-class contaminants
      in edible seaweeds by gas chromatography-mass spectrometry.
AB  - The present work aimed at the development of a simple and accurate direct
      immersion-solidphase microextraction-gas-chromatography-mass spectrometry (DI
      SPME-GC-MS) method for simultaneous determination of PAHs, PCBs, and pesticide
      residues in edible seaweeds. As the target contaminants possess a wide range of
      physical-chemical properties, multivariate experimental design was used for
      method optimization. In particular, two different methods were optimized and
      validated: one that allows for simultaneous determination of all targets, and an
      ad hoc method for determination of hydrophobic analytes, a class that often poses
      a challenge for extraction from food matrices. Optimum conditions suitable for
      simultaneous quantitation of all targeted compounds, namely buffer at pH = 7.0,
      20% acetone (v/v), 10% NaCl (w/w), 0.02% NaN3, 60 min DI extraction at 55 
      degrees C, and 20 min desorption at 270  degrees C, afforded limits of
      quantitation (LOQs) in the range of 1-30 MUg kg-1, a wide linear range of 5-2000
      MUg kg-1, the attainment of satisfactory determination coefficients (R2?0.99)
      with no significant lack of fit (p > 0.05) at the 5% level, and satisfactory
      accuracy and precision values. By modifying the extraction conditions to favor
      extraction of the most hydrophobic analytes (e.g. higher amount of organic
      modifier and pH, and lower salt content) lower LOQs were obtained for these
      compounds ranging from 0.2 to 13.3 MUg kg-1. The established methods were then
      used for screening of commercial, edible dry seaweeds, with PCBs (<=16.0 ng g-1)
      and PAHs (<=15.5 ng g-1) detected in some samples. This method overcomes most
      challenges commonly encountered in dry sample analysis applications, and
      represents the first report of a DI-SPME method employing the matrix-compatible
      fiber for simultaneous multiclass and multiresidue analysis of seaweeds.

PMID- 30119748
TI  - Simultaneous measurement of fifteen rare earth elements using diffusive gradients
      in thin films.
AB  - A new method for simultaneous measurement of fifteen rare earth elements (REEs)
      [La (III), Ce (III), Pr (III), Nd (III), Sm (III), Eu (III), Gd (III), Tb (III),
      Dy (III), Ho (III), Er (III), Tm (III), Yb (III), Lu (III), and Y (III)] was
      established in this study using the diffusive gradients in thin films (DGT)
      technique with Chelex(r)100 binding gel. Five different types of ion exchange
      resins (Chelex(r)100, D418, D001-cc, 001 * 7, and HSTY(r)-SS) were selected for
      the initial investigation of their adsorption performance for REEs. The
      Chelex(r)100 binding gel had the greatest uptake efficiencies of >95% for the
      fifteen REE ions, which was used for all subsequent experiments. The binding gel
      exhibited rapid binding dynamics to REEs in mixed solution of the fifteen REE
      ions. Elution efficiencies ranging from 86.5% to 93.8% for these REEs were
      obtained based on extraction using 2.0 M HCl. The Chelex(r)100 DGT uptake of the
      fifteen REE ions increased linearly with the deployment time and found to be
      independent of pH (3-9) and ionic strength (3 mM-100 mM). The capacities of
      Chelex(r)100 DGT for measurement of the mixed elements were determined at a range
      of 5.39-6.75 MUg cm-2. Application of the DGT for soil analysis showed that
      Chelex(r)100 DGT was a useful tool in simultaneous measurement of the fifteen REE
      ions, even in a soil with high concentrations of REEs. This study demonstrated
      the advantage of Chelex(r)100 DGT in simultaneous measurement of the fifteen REE
      ions due to high uptake efficiencies and a wide tolerance to environmental
      interference.

PMID- 30119749
TI  - Mere Membership.
AB  - Human social groups are central to social organization and pervasively impact
      interpersonal interactions. Although immensely varied, all social groups can be
      considered specific instantiations of a common and abstract ingroup-outgroup
      structure. How much of the power of human social groups stems from learned
      variation versus abstract commonality? I review evidence demonstrating that from
      early in development a wide range of intergroup phenomena, most prominently many
      ingroup biases, follow solely from simple membership in an abstract social
      collective. Such effects cannot be attributed to rich social learning, and thus
      (i) constrain theories seeking to explain or intervene on ingroup bias, and (ii)
      provide reason to think that our species is powerfully predisposed towards
      ingroup favoritism from early in development.

PMID- 30119750
TI  - Children and youth are crucial in the global AIDS response.

PMID- 30119751
TI  - The search for effective behavioural approaches for adolescent type 1 diabetes
      management.

PMID- 30119752
TI  - The hazards of out-of-home care for children experiencing adverse home
      environments.

PMID- 30119753
TI  - Failure to adequately protect adolescents presenting to London sexual assault
      services.

PMID- 30119755
TI  - Neonatal opioid withdrawal in the USA.

PMID- 30119754
TI  - Near infrared investigation of the infants' brain.

PMID- 30119756
TI  - Navigating teenage cancer.

PMID- 30119758
TI  - Out-of-home placement in early childhood and psychiatric diagnoses and criminal
      convictions in young adulthood: a population-based propensity score-matched
      study.
AB  - BACKGROUND: To ensure their protection and healthy development, children exposed
      to adverse family circumstances might be placed in foster homes, institutions, or
      kinship care (out-of-home placement). We aimed to compare the rates of
      psychiatric diagnoses and criminal convictions in young adulthood (ages 18-25
      years) among children who were first placed at ages 2-6 years with those of
      children who were not placed and who had similar sociodemographic and family
      characteristics. METHOD: We did a population-wide cohort study using the 1987
      Finnish Birth Cohort, which collects longitudinal data linking nationwide child
      welfare, medical, and criminal registers for all 59 476 livebirths in Finland in
      1987. The exposure was the first out-of-home placement at ages 2-6 years.
      Outcomes were rates of psychiatric diagnoses, criminal convictions, and
      prescriptions for psychotropic medication filled at ages 18-25 years. We matched
      cases to non-placed controls using propensity score matching on parental
      characteristics (eg, age, psychiatric diagnoses, education, family structure) and
      child characteristics (eg, neurodevelopmental problems, prematurity). Differences
      in adult outcomes between children placed and matched controls were assessed by
      use of logistic regression on the matched cohort. FINDINGS: Of 54 814 individuals
      with complete data, 388 (1%) were first placed at ages 2-6 years; matched
      controls were identified for 386 of these children. At ages 18-25 years, those
      who had been placed as children had greater odds than never-placed controls of
      substance-related disorders (odds ratio 2.10, 95% CI 1.27-3.48), psychotic or
      bipolar disorders (3.98, 1.80-8.80), depression or anxiety (2.15, 1.46-3.18),
      neurodevelopmental disorders (3.59, 1.17-11.02), or other disorders (2.06, 1.25
      3.39). Participants who were placed had more psychotropic medication
      prescriptions (1.96, 1.38-2.80) and higher rates of criminal convictions (violent
      offences, 2.43, 1.61-3.68; property offences, 1.86, 1.17-2.97). INTERPRETATION:
      Preschool children who are placed out-of-home are at risk of adverse outcomes as
      adults, even accounting for their initial circumstances. It is important to
      explore which conditions lead to more or less favourable outcomes in child
      protection. FUNDING: Academy of Finland.

PMID- 30119759
TI  - Mental and sexual health outcomes following sexual assault in adolescents: a
      prospective cohort study.
AB  - BACKGROUND: Young people are disproportionately affected by sexual assault, yet
      longitudinal data are sparse. This paper examines the characteristics of
      adolescents presenting to sexual assault services and mental and sexual health
      outcomes after an assault. METHODS: This was a prospective cohort study in
      adolescents aged 13-17 years attending the Sexual Assault Referral Centres
      serving Greater London, UK, over 2 years. Baseline interviews (T0) were done less
      than 6 weeks after an assault to collect data on sociodemographic and assault
      characteristics and psychological symptoms, with follow-up interviews (T1) at 4-5
      months after the assault. Four psychological symptom questionnaires were used at
      T0 and T1: The Child Revised Impact of Events Scale, the Short Mood and Feelings
      Questionnaire, the Screen for Child Anxiety Related Disorders, and the Strengths
      and Difficulties Questionnaire. The primary outcome was prevalence of any
      psychiatric disorder at T1, assessed using the Development and Wellbeing
      Assessment. Secondary outcomes at T1 were pregnancy, sexually transmitted
      infections, and sexual health screening since the assault. FINDINGS: Between
      April 15, 2013, and April 20, 2015, 141 (29%) of 491 eligible young people were
      recruited to the study (134 females; mean age 15.6 years [SD 1.27]), and 106
      (75%) of 141 participants had T1 interviews (99 female). At T0, psychological
      symptom scores showed that 115 (88%) of 130 females were at risk for depressive
      disorder, 90 (71%) of 126 were at risk for anxiety disorders, and 116 (91%) of
      128 were at risk for post-traumatic stress disorder, with symptoms largely
      persisting at T1. 68 (80%) of 85 females who had a diagnostic assessment at T1
      had a psychiatric disorder, with multiple disorders in 47 (55%) of 85. Anxiety,
      post-traumatic stress, and major depressive disorders were the commonest
      diagnoses. Presence of a psychiatric disorder was associated with baseline
      psychosocial vulnerability (previous social services involvement, mental health
      service use, self-harm, or sexual abuse), but not assault characteristics. At T1,
      four (4%) of 105 females had been pregnant since the assault, 14 (12%) of 119 had
      a sexually transmitted infection diagnosed between T0 and T1, and nine (8%) of
      107 reported re-victimisation since the assault. INTERPRETATION: Vulnerable
      adolescents have the double disadvantage of being at risk for both sexual assault
      and associated psychiatric disorders, highlighting the need for comprehensive
      support after an assault. Feasibility and effectiveness of prevention programmes
      should be investigated. FUNDING: National Institute for Health Research Policy
      Research Programme grant (115/0001).

PMID- 30119760
TI  - Perinatal stroke: mechanisms, management, and outcomes of early cerebrovascular
      brain injury.
AB  - Perinatal stroke encompasses a heterogeneous group of focal neurological injuries
      early in brain development that probably affects more than 5 million people
      worldwide. Many such injuries are symptomatic in the first days of life,
      including neonatal arterial ischaemic stroke, cerebral sinovenous thrombosis, and
      neonatal haemorrhagic stroke. The remaining focal neurological injuries usually
      present later in the first year with motor asymmetry, such as arterial presumed
      perinatal ischaemic stroke, periventricular venous infarction, and presumed
      perinatal haemorrhagic stroke. The numerous sequelae of these injuries include
      hemiparesis (cerebral palsy), epilepsy, and cognitive, language, and behavioural
      challenges. In this Review we summarise each perinatal stroke disease, examining
      the epidemiology, pathophysiology, acute management, and outcomes, including the
      effect on parents and families, and emerging therapies to mitigate these lifelong
      morbidities.

PMID- 30119757
TI  - Efficacy of the Flexible Lifestyles Empowering Change intervention on metabolic
      and psychosocial outcomes in adolescents with type 1 diabetes (FLEX): a
      randomised controlled trial.
AB  - BACKGROUND: Adolescents with type 1 diabetes commonly have poor glycaemic
      control. We aimed to test the efficacy of a newly developed adaptive behavioral
      intervention (Flexible Lifestyles Empowering Change; FLEX) on metabolic and
      psychosocial outcomes in adolescents with type 1 diabetes. METHODS: Young people
      (13-16 years, type 1 diabetes duration >1 year, HbA1c of 64-119 mmol/mol [8.0
      13.0%], and without other serious medical conditions or pregnancy) from two
      clinical sites (Colorado and Ohio, USA) were eligible for enrolment. One
      caregiver was required to participate actively in the study. Adolescent
      participants were randomly assigned to the FLEX intervention, which used
      motivational interviewing and problem-solving skills training to enhance
      patients' self-management, or usual care control. Intervention fidelity was
      assessed by a behavioral psychologist with specific expertise in motivational
      interviewing and who was not otherwise involved in the study via audiotaped
      sessions. The primary outcome was measurement of glycated haemoglobin A1c (HbA1c)
      at 18 months. Secondary outcomes included motivation and intention, problem
      solving skills, self-management behaviors, symptoms of depression, health related
      quality of life, fear of hypoglycemia, diabetes family conflict, risk factors for
      T1D complications (BMI, blood pressure, and plasma lipids), and hypoglycemia
      derived from continuous glucose monitoring (percent time below 3.0 and 3.9 mmol/l
      [54 and 70 mg/dl]). Intention-to-treat analyses used mixed effects models, with
      fixed effects including site, timepoint, intervention group, intervention by
      timepoint, and baseline level of primary (HbA1c) or secondary outcomes
      (alpha=0.05). FLEX is registered on clinicaltrials.gov, number NCT01286350.
      FINDINGS: Young people recruited from May 1, 2014 to April 4, 2016 were randomly
      assigned to FLEX (n=130) or usual care control (n=128). Mean diabetes duration
      was 6.4 (SD 3.8) years, and 71% (181 out of 256) of patients used insulin pump
      therapy. Retention was 93%, with 241 out of 258 completing the 18-month
      assessment. The intervention fidelity score was 4.40 of 5.00 for motivational
      interviewing and 97% for session content. At 18 months, HbA1c was not
      significantly different between intervention (83 [13] mmol/mol at baseline; 84
      [19] mmol/mol at follow-up); and control (80 [14] mmol/mol at baseline; 82 [17]
      mmol/mol at follow-up); change in intervention versus control was -0.7 mmol/mol
      (95% CI -4.7 to 3.4, p=0.75). The intervention was associated with improved
      scores for motivation (p=0.011), problem solving (p=0.024), diabetes self
      management profile (p=0.013), youth report of overall quality of life (p=0.0089),
      selected domains related to fear of hypoglycaemia (p=0.036 for youth's
      helplessness or worry; p=0.0051 for parent's efforts to maintain high blood
      glucose), parent report of diabetes family conflict (p=0.0001), total cholesterol
      (p=0.038), and diastolic blood pressure (p=0.015). A total of 54 serious adverse
      events were identified; 34 of these were diabetes-related, including low blood
      glucose requiring assistance (n=3) and high blood glucose with diabetic
      ketoacidosis and emergency response (n=25). INTERPRETATION: The FLEX intervention
      did not significantly change HbA1c among these adolescents with elevated HbA1c,
      but did positively affect several psychosocial outcomes over 18 months. Further
      analyses will provide information regarding drivers of positive response to the
      intervention and will point to future directions for improvement in the approach.
      FUNDING: National Institutes of Health and National Institute of Diabetes
      Digestive Diseases and Kidney and the Helmsley Charitable Trust.

PMID- 30119761
TI  - Amenorrhoea in adolescent female athletes.
AB  - Female athletes often experience amenorrhoea at various times during training,
      but this should not be considered normal. Low energy availability is a common
      cause of menstrual dysfunction, and amenorrhoea can serve as a warning sign of
      some of the health and performance consequences associated with inadequate
      energy, including poor bone accrual and low bone mineral density. Adolescence is
      an important time for bone accrual, growth, and development, making delayed
      menarche and secondary amenorrhoea particularly concerning in young athletes. The
      development of disordered eating and eating disorder behaviours also peaks during
      adolescence. Thus, screening for low energy availability, establishing the
      various causes of amenorrhoea, and treating amenorrhoea and low energy
      availability with an interdisciplinary team is most effective.

PMID- 30119763
TI  - Screening performance of consensus definition of fetal growth restriction
      inappropriately evaluated.

PMID- 30119762
TI  - Demand avoidance is not necessarily defiance - Authors' reply.

PMID- 30119764
TI  - Screening performance of consensus definition of fetal growth restriction
      inappropriately evaluated - Authors' reply.

PMID- 30119765
TI  - Correction to Lancet Child Adolesc Health 2018; 2: 582-90.

PMID- 30119766
TI  - Computed Tomography Enterography.
AB  - Computed tomography (CT) enterography is a noninvasive imaging modality with
      superb spatial and temporal resolution, specifically tailored to evaluate the
      small bowel. It has several advantages over other radiologic and optical imaging
      modalities, all of which serve as complementary investigations to one another.
      This article describes CTE technique, including dose reduction techniques,
      special considerations for the pediatric population, common technical and
      interpretive pitfalls, and reviews some of the more common small bowel entities
      seen with CTE.

PMID- 30119767
TI  - Magnetic Resonance Enterography for Inflammatory and Noninflammatory Conditions
      of the Small Bowel.
AB  - Magnetic resonance enterography (MRE) is an effective noninvasive tool for
      evaluation of inflammatory and noninflammatory conditions of the small bowel. MRE
      allows for repeated evaluation of patients with Crohn disease without exposure to
      ionizing radiation, and can be used to assess disease status and direct
      management. MRE also allows evaluation of neoplastic and other nonneoplastic
      conditions of the small bowel. Adequate patient preparation and acquisition
      techniques are required for optimal image quality.

PMID- 30119768
TI  - Interdisciplinary Updates in Crohn's Disease Reporting Nomenclature, and Cross
      Sectional Disease Monitoring.
AB  - Computed tomography enterography and magnetic resonance enterography are
      essential in the evaluation and treatment of patients with Crohn's disease. As
      such, examination reporting must use standardized nomenclature for effective
      communication. This report documents an interdisciplinary consensus of the
      Society of Abdominal Radiology, the Society of Pediatric Radiology, and the
      American Gastroenterology Association on the computed tomography
      enterography/magnetic resonance enterography imaging findings and imaging-based
      morphologic phenotypes.

PMID- 30119770
TI  - Computed Tomography Colonography: Pearls and Pitfalls.
AB  - This article serves as a practical reference to optimize the performance of
      computed tomography colonography in the detection of colorectal neoplasia. A
      specific protocol in use at 2 US university programs as well as defined
      interpretation strategies will be described. With this framework in place,
      various clinical pearls as well as pitfalls to avoid will be a major focus of
      this article.

PMID- 30119769
TI  - Low-Dose Computed Tomography Colonography Technique.
AB  - Significant anxiety has been expressed by some over the radiation risks
      associated with computed tomography (CT), particularly when it applies to a
      screening examination such as CT colonography. These theoretic risks are far
      outweighed by the significant benefits colorectal cancer screening offers.
      Regardless of how significant the theoretic risk of CT radiation is in the older
      population, the ALARA principle maintains that radiation dose should be reduced
      to As Low As Reasonably Achievable. This article will discuss various strategies
      that may be utilized to reduce radiation dose and mitigate any increase in image
      noise that may occur.

PMID- 30119771
TI  - Current Status of Magnetic Resonance Colonography for Screening and Diagnosis of
      Colorectal Cancer.
AB  - Magnetic resonance colonography with its high tissue contrast and without the use
      of ionizing radiation was designed as a minimally invasive screening tool for
      colorectal cancer and its precursors. Nonetheless, heterogeneous data on
      diagnostic performance and patient burden have hindered its use in screening.
      This article provides an overview on the status and potential of magnetic
      resonance colonography in the setting of detection and screening of colorectal
      cancer and its precursors.

PMID- 30119772
TI  - MR Imaging of Rectal Cancer.
AB  - This article aims to review current concepts in the management of patients with
      rectal cancer, including the most common surgical techniques, anatomic landmarks
      with MR imaging correlation, and the role of each imaging modality in local
      staging, focusing on MR imaging technique and its importance in primary staging,
      restaging, and local recurrence.

PMID- 30119773
TI  - MR Imaging of Perianal Fistulas.
AB  - In this article, we begin with an introduction of the perianal region anatomy,
      then review the definition, etiology, epidemiology, and 2 major classification
      systems of perianal fistulas. The role of MR imaging for assessment of perianal
      fistulas is mainly discussed. Finally, the medical and surgical treatment
      principles are reviewed.

PMID- 30119774
TI  - Imaging Workup of Acute and Occult Lower Gastrointestinal Bleeding.
AB  - Lower gastrointestinal bleeding is defined as occurring distal to the ligament of
      Treitz and presents as hematochezia, melena, or with anemia and positive fecal
      occult blood test. Imaging plays a pivotal role in the localization and treatment
      of lower gastrointestinal bleeds. Imaging tests in the workup of acute lower
      gastrointestinal bleeding include computed tomography (CT) angiography, nuclear
      medicine scintigraphy, and conventional catheter angiography. Catheter
      angiography can also be used to deliver treatment. Imaging tests in the workup of
      occult lower gastrointestinal bleeding include CT enterography and nuclear
      medicine Meckel scan.

PMID- 30119775
TI  - Dual Energy Computed Tomography Scans of the Bowel: Benefits, Pitfalls, and
      Future Directions.
AB  - Current computed tomography bowel imaging is challenging given the variable
      distension, content, and location of the bowel, the different appearance of
      tumors within and adjacent to bowel, and peristaltic artifacts. Published data
      remain sparse. Derangements in enhancement may be highlighted, image artifacts
      reduced, and radiation dose from multiphase scans minimized. This modality is
      suited for imaging bowel tumor detection and characterization, gastrointestinal
      bleeding, and bowel inflammation, and ischemia. Experimental results on computed
      tomography colonography and novel bowel contrast material offer hope for major
      improvements in bowel interrogation. It is likely to become increasingly valuable
      for bowel-related disease diagnosis and monitoring.

PMID- 30119776
TI  - Lower Gastrointestinal Tract Applications of PET/Computed Tomography and PET/MR
      Imaging.
AB  - This article discusses the role of PET/CT and PET/MR imaging in the evaluation of
      inflammatory and malignant disorders of the lower gastrointestinal tract. This
      includes a review of the current literature and a discussion of new and emerging
      research.

PMID- 30119777
TI  - Imaging of the Postoperative Colon.
AB  - Recognition of postoperative complications is important for the immediate
      diagnosis and treatment needed for appropriate patient care. Identification of
      postoperative complications from colon surgery requires not only knowledge of the
      type of procedure, but also the expected normal postoperative appearance. The
      purpose of this article is to discuss and review the expected anatomic changes
      after colorectal surgery, and the appearance of the most common postoperative
      complications.

PMID- 30119778
TI  - Innovations in Bowel Imaging.

PMID- 30119779
TI  - Editorial - The Bibliometric Measurements of the Polish Journal of Neurology and
      Neurosurgery (Neurologia i Neurochirurgia Polska) for 2017.

PMID- 30119780
TI  - Electronic screens and children's vision: development of a joint position
      statement.

PMID- 30119781
TI  - Les ecrans electroniques et la vision des enfants: Elaboration d'un enonce de
      principe commun.

PMID- 30119782
TI  - Deep learning in ophthalmology: a review.
AB  - Deep learning is an emerging technology with numerous potential applications in
      Ophthalmology. Deep learning tools have been applied to different diagnostic
      modalities including digital photographs, optical coherence tomography, and
      visual fields. These tools have demonstrated utility in assessment of various
      disease processes including cataracts, glaucoma, age-related macular
      degeneration, and diabetic retinopathy. Deep learning techniques are evolving
      rapidly, and will become more integrated into ophthalmic care. This article
      reviews the current evidence for deep learning in ophthalmology, and discusses
      future applications, as well as potential drawbacks.

PMID- 30119783
TI  - Systemic immunosuppression in limbal stem cell transplantation: best practices
      and future challenges.
AB  - The objective of this study was to evaluate systemic immunosuppression regimens
      used for patients undergoing ocular surface stem cell transplantation, including
      their benefits and adverse effects in the adjunctive management of limbal stem
      cell deficiency (LSCD). A systematic literature review was conducted using the
      MEDLINE and EMBASE databases (1980-2015). Data were collected on surgical
      intervention(s), type of immunosuppressive agent(s), duration of
      immunosuppression, percentage with stable ocular surface at last follow-up, mean
      follow-up time, and demographics. Data were also collected on adverse ocular and
      systemic outcomes. Sixteen reports met the inclusion criteria. There were no
      randomized controlled studies. Three studies were noncomparative prospective case
      series, whereas the majority were retrospective case series. Bilateral severe
      LSCD was the most common disease (50%), and keratolimbal allograft was the most
      common intervention (80%). Immunosuppressive regimens showed a progression from
      early studies using oral cyclosporine to later studies using combinations of
      mycophenolate mofetil and tacrolimus. Most studies included a course of high-dose
      systemic corticosteroids. For patients adherent to long-term systemic
      immunosuppression, stable ocular surface rates of 70%-80% at last follow-up were
      reported. Adverse effects included hypertension, diabetes mellitus, and
      biochemical abnormalities managed with pharmacotherapy or discontinuation of
      offending agents. There were no cases of mortality related to immunosuppression.
      However, the current literature does not elucidate which immunosuppressive
      regimen is most efficacious for different categories of LSCD or graft types.
      Evidence-based guidelines for systemic immunosuppression in limbal allograft
      therapy would benefit from randomized controlled and/or additional prospective
      studies. Long-term immunosuppression would benefit from close collaboration
      between ophthalmologists and transplant specialists to individualize treatments.

PMID- 30119784
TI  - Femto-second laser (FSL) techniques and consistency in corneal surgery:
      experimental study.
AB  - OBJECTIVE: To investigate the feasibility, effectiveness, and reproducibility of
      femtosecond laser (FSL) technology in different corneal cuts. DESIGN:
      Experimental study at the Brandon Regional Health Centre. PARTICIPANTS: Twenty
      two Human Cadaver eyes donated for research and supplied by the eye bank of
      Manitoba university. METHODS: In this experimental study, the effectiveness and
      reproducibility of FSL were investigated in different corneal cuts. The corneas
      were divided into 5 groups: group I for penetrating keratoplasty; group II for
      anterior lamellar keratoplasty; group III for corneal pockets for inlays; group
      IV for intracorneal ring tunnels; and group V for corneal cross-linking pockets.
      Our primary endpoint was the repeatability of planned versus obtained thickness
      and diameter of the cuts with FSL. A secondary endpoint was the effectiveness and
      ease of dissection, rated from 0-4, with 4 being the easiest and 0 the most
      difficult to dissect. RESULTS: There was a high correlation between planned and
      obtained thickness (r = 0.997, p < 0.001) and diameter (r = 0.998, p < 0.001).
      Both were statistically significant. Linear regression analyses showed that the
      obtained thickness of corneal cuts in micrometers was significantly predicted by
      the planned thickness of corneal cuts in micrometers (beta = 0.996, t = 56.47, p
      < 0.001). Likewise, the obtained diameter of corneal cuts in millimeters was
      significantly predicted by the planned diameter of corneal cuts in millimeters
      (beta = 0.971, t = 70.85, p < 0.001). The surgeons gave 15 out of a total of 22
      corneas (68.2%) the maximum score for ease of dissection (Grade 4), where no
      adhesions were found and the dissection was smooth and steady. Five corneas out
      of a total of 22 (22.7%) were given a score of 3 of 4 where minor adhesions were
      found. Two corneas out of a total of 22 (9.1%) were given a score of 2 of 4 where
      >1 adhesion was found, with some difficulty in separating the cut cornea from the
      bed. No corneas were given grade 1 or grade 0. No significant differences were
      obtained for the ease of dissection among the 5 surgery types using Kruskal
      Wallis H test (H [4] = 4.971, p > 0.05). CONCLUSION: The measured corneal-cut
      geometry correlated well with laser settings in a variety of full- and partial
      thickness FSL corneal patterns, including different depths and diameters. This
      reproducible efficacy and measurement accuracy of the planned versus obtained
      cuts could have a favourable result on a variety of corneal surgeries. It also
      yields a favourable ease of dissection of the cut lenticule from the stromal bed.

PMID- 30119786
TI  - Immediate sequential bilateral cataract surgery: surgeon preferences and
      concerns.
AB  - OBJECTIVE: We surveyed cataract surgeons to gain insight into their perceptions
      of and attitudes about immediate sequential bilateral cataract surgery (ISBCS).
      DESIGN: Cross-sectional. PARTICIPANTS: All active cataract surgeons in Kaiser
      Permanente Northern California in 2016. METHODS: Online survey that asked
      cataract surgeons why they did or did not perform ISBCS, their interest in
      offering ISBCS, concerns about the procedure, and desired supports. RESULTS: Of
      the 165 active cataract surgeons, 107 (65%) participated in the survey, of whom
      92 (86%) responded that they currently practiced ISBCS and 15 (14%) reported that
      they did not. For ISBCS surgeons, patient convenience (95%) and patient request
      (91%) were the top reasons for performing the procedure. For surgeons who do not
      perform ISBCS, the most commonly cited concerns were not having the postoperative
      refractive outcome from the first eye to guide intraocular lens selection in the
      second eye (80%) and risk of bilateral vision loss (73%). Among those who do not
      perform ISBCS, 9 (60%) identified the need for evidence-based patient selection
      criteria to support a decision to adopt the procedure. In addition, many surgeons
      in both groups wanted streamlined patient education materials and established
      protocols. CONCLUSION: Patient centeredness is a key construct of contemporary
      health care delivery, and in an era of low complication risk, many patients
      request ISBCS; the number of these surgeries has increased. In our capitated
      health care system, the great majority of surgeons perform ISBCS for the
      convenience of their patients. Providing surgeons with guidelines and tools to
      support ISBCS likely would increase adoption.

PMID- 30119785
TI  - Epidemiology of bacterial corneal ulcers at tertiary centres in Vancouver, B.C.
AB  - OBJECTIVE: To report the epidemiology of culture-positive bacterial corneal
      ulcers in Vancouver, B.C., Canada. DESIGN: Retrospective, observational case
      series. METHODS: Predetermined search terms were entered into the hospitals'
      electronic microbiology databases to create a cohort of patients who had
      undergone corneal scrapings for ulcers from April 2006 to March 2011. All
      specimens were plated on culture media. Cultured species were identified, and
      antimicrobial sensitivities were obtained. Clinical charts were then reviewed to
      identify associated risk factors. RESULTS: In total 281 corneal scrapings were
      included, with a positive culture recovery rate of 75%. Bacterial keratitis
      accounted for 84.8% of culture-positive ulcers, followed by fungi (10%) and
      finally Acanthamoeba (5.2%); 73% of ulcers were monomicrobial in origin and 28%
      polymicrobial. We found an increase in Gram-negative micro-organisms over time.
      General sensitivity to antibiotics did not change over time. A major risk factor
      for Gram-positive involvement was ocular surface disease, whereas contact lens
      wear was a major risk factor for Gram-negative involvement. CONCLUSIONS:
      Bacterial keratitis was found to be the major cause of infectious keratitis in
      Vancouver, B.C. The majority of bacterial ulcers were caused by Gram-positive
      bacteria. However, we found an increase in Gram-negative involvement over time.
      Contact lens wear was identified as the major risk factor for development of Gram
      negative ulcers. Pre-existing ocular disease was associated with Gram-positive
      infection. Susceptibility of Gram-negative bacteria to common broad-spectrum
      antibiotics was high, but susceptibility of Gram-positive bacteria to these
      antibiotics was lower and more variable.

PMID- 30119787
TI  - Eye care utilisation in Newfoundland and Labrador: access barriers and vision
      health outcomes.
AB  - OBJECTIVE: Our prior study revealed significantly lower use of eye care providers
      in Newfoundland and Labrador (NFLD). This study reports factors associated with
      this low use and related vision health outcomes. DESIGN: Cross-sectional survey.
      PARTICIPANTS: A total of 14 925 Caucasian respondents to the Canadian Community
      Health Survey - Healthy Aging 2008/2009 aged >=65 years. METHODS: Univariate and
      multivariate analyses were performed using self-reported survey data. RESULTS:
      NFLD, along with 3 other provinces, does not insure seniors for routine eye
      examinations. Among seniors without self-reported glaucoma, cataracts, and
      diabetes, the use of eye care providers in NFLD (36.3%) is the lowest compared
      with provinces with (50.7%, p < 0.05) and without (42.2%, p > 0.05) government
      insured eye examinations. Among seniors with known eye disease insured for eye
      care in all provinces, eye care utilisation in NFLD (63.1%) is still the lowest
      across all provinces (69.4%-71.3%, p > 0.05). Compared with the national average,
      NFLD seniors have significantly higher proportions of low income (61.7% vs
      47.4%), no postsecondary education (53.6% vs 42.2%), and rural residency (40.6%
      vs 18.9%). These factors are all associated with low levels of eye care
      utilisation. Compared with insured provinces, NFLD has a significantly lower
      prevalence of self-reported cataracts (16.7% vs 23.1) and glaucoma (3.8% vs
      7.0%), and a slightly higher prevalence of presenting visual impairment (4.0% vs
      3.5%). CONCLUSIONS: Lack of government insurance, low socioeconomic status, and
      living in nonurbanised areas all contribute to the underutilisation of eye care
      providers in NFLD. This underutilisation appears to be associated with reduced
      detection of eye diseases.

PMID- 30119788
TI  - Methotrexate for the treatment of noninfectious scleritis.
AB  - OBJECTIVE: To assess corticosteroid-sparing and inflammation control in patients
      with noninfectious scleritis treated with methotrexate. DESIGN: Retrospective
      review. PARTICIPANTS: Patients who received methotrexate treatment for
      noninfectious scleritis and who had 12 months of follow-up after treatment
      initiation were included in this review. METHODS: The clinical records of
      noninfectious scleritis patients presenting at the University of Ottawa Eye
      Institute between September 1, 2010 and December 31, 2014 treated with
      methotrexate were retrospectively reviewed. Seventeen patients (21 eyes) were
      included in the study. Main outcome included inflammation control and
      corticosteroid-sparing success. Secondary outcomes were reduction of
      immunosuppression load and best-corrected visual acuity. RESULTS: The proportion
      of eyes with corticosteroid-sparing success was 69.2% at 3 months and 92.3% at 12
      months. The proportion of eyes that achieved inflammation control was 61.9% at 3
      months and 90.5% at 12 months. The corticosteroid immunosuppression load at
      treatment start was 1.9 +/- 2.07 and at 12 months was 0.48 +/- 1.03 (p < 0.01).
      There was no statistically significant difference in best-corrected visual
      acuity. CONCLUSIONS: The treatment of noninfectious scleritis with methotrexate
      appears to be effective at both achieving steroid-sparing success and controlling
      inflammation during 12 months of therapy. Immunosuppression load decreased
      significantly over 12 months of therapy while best corrected visual acuity was
      stable.

PMID- 30119789
TI  - Depression and quality of life in a community-based glaucoma-screening project.
AB  - OBJECTIVE: To identify the prevalence and risk factors of depression among
      individuals given a glaucoma-related diagnosis at a screening program. DESIGN:
      Cross-sectional community-based in a university hospital. PARTICIPANTS:
      Volunteers from a community glaucoma-screening program. METHODS: After collecting
      sociodemographic information, participants were administered the Geriatric
      Depression Scale-15 (GDS-15) and the National Eye Institute Visual Function
      Questionnaire-25 (NEI-VFQ-25). RESULTS: Participants were predominantly African
      American (73.5%), older than 65 years (65.7%), single (75.4%), and female
      (66.8%). Among 268 participants, 89 were diagnosed with glaucoma and 179 as
      glaucoma suspects. The frequency of depression among the glaucoma and glaucoma
      suspect participants was 18% and 16.2%, respectively. The mean GDS-15 score was
      2.4 +/- 2.7 with no difference between glaucoma and glaucoma suspect groups, p =
      0.654. The mean VFQ-25 score was 78.6 +/- 15.9 and was lower in glaucoma (74.7 +/
      19.7) than glaucoma suspect participants (80.4 +/- 13.6), p = 0.003. Risk
      factors for depression included difficulties with paying expenses (p = 0.017),
      Asian race (p < 0.001), and poorer scores on the VFQ-25 subscales of "General
      Health" (p < 0.001), "Distance Activities" (p = 0.024), and "Dependency" (p =
      0.001). CONCLUSIONS: Prevalence of depression in those diagnosed with glaucoma or
      glaucoma suspect was higher than previous estimates of the general population.
      Glaucoma-screening programs might benefit from including depression-screening
      protocols along with referral services or low-cost treatments of depression.

PMID- 30119790
TI  - Ab interno trabeculectomy with Trabectome: outcomes in African American versus
      Caucasian patients.
AB  - OBJECTIVE: To compare the intraocular pressure-lowering efficacy and complication
      rate of ab interno trabeculectomy with the Trabectome between African American
      (AA) and Caucasian patients with open-angle glaucoma. METHODS: A total of 164
      patients (82 AA and 82 Caucasian) who underwent ab interno trabeculectomy over an
      8-year period were included in this prospective, case-control study. The Neomedix
      database was used to look for AA or Caucasian patients with open-angle glaucoma
      who underwent Trabectome with or without phacoemulsification. RESULTS: The
      average IOP of AA patients was reduced from 21.2 +/- 6.8 mm Hg to 16.1 +/- 4.1 mm
      Hg at 12 M (p < 0.01), and the mean number of glaucoma medications was reduced
      from 2.4 +/- 1.3 to 2.0 +/- 1.4 (p = 0.13). Among Caucasians, the mean IOP was
      reduced from 21.2 +/- 6.8 mm Hg to 15.7 +/- 4.2 mm Hg at 12 M (p < 0.01), and the
      number of medications dropped from 2.4 +/- 1.2 to 1.7 +/- 1.3 (p < 0.01). No
      statistically significant difference was found between these 2 race groups in
      IOP, number of medications, and complications. For complications with Trabectome
      alone, 13% of AA and 9% of Caucasian patients needed secondary surgery. There was
      only 1 case of hypotony which was in the AA group. For complications with
      Trabectome combined with phacoemulsification, 4% of AA as well as 4% of Caucasian
      patients required secondary surgery. There was only 1 case of hypotony which was
      in the Caucasian group. CONCLUSION: Ab interno trabeculectomy with Trabectome is
      associated with a reduction in IOP in both race groups with a similar
      complication and survival profiles.

PMID- 30119791
TI  - Association of pseudoexfoliation syndrome with cardiovascular and cerebrovascular
      disease: a systematic review and meta-analysis.
AB  - OBJECTIVE: Pseudoexfoliation syndrome (PEX) is a systemic disease, but evidence
      of its association with cardiovascular disease (CVD) and cerebrovascular disease
      (CVA) is controversial. A quantitative systematic review will provide an accurate
      summary of the current body of the literature. DESIGN: Meta-analysis.
      PARTICIPANTS: Not applicable. METHODS: A comprehensive literature search of
      published and unpublished English-language studies was performed. Summary
      statistics were calculated using inverse variance weighting and are presented in
      forest plots. Sources of variance were evaluated statistically. RESULTS: After
      screening 4547 studies, 47 articles were reviewed, and 25 eligible studies were
      selected that reported patients from around the world. Twenty studies enrolling
      9583 individuals with PEX evaluated CVD, providing a summary odds ratio (OR) of
      1.61 (95% CI 1.37-1.90). Eleven studies, enrolling 1308 PEX patients, evaluated
      CVA and generated a summary OR of 1.76 (1.40-2.22). For any vascular event (AVE)
      using all 25 studies, there were 9716 PEX patients and 363,312 control patients,
      yielding a summary OR of 1.64 (95% CI 1.39-1.92). Analysis for publication bias
      with the Egger's test was not significant for studies reporting CVD and AVE (p =
      0.92 and 0.64, respectively) but was significant for CVA (p = 0.03). Asymmetry of
      Begg's funnel plot was noted for the CVA and AVE analyses. Multiple sensitivity
      analyses were performed, including assessment of study quality; the OR for all 3
      outcomes varied minimally and remained significant in all analyses. CONCLUSION:
      There is strong evidence that PEX is significantly associated with both CVD and
      CVA.

PMID- 30119792
TI  - Functional and structural evaluation of the meibomian gland using a LipiView
      interferometer in thyroid eye disease.
AB  - OBJECTIVE: The purpose of this study was to evaluate the structure and function
      of the meibomian gland and the incomplete blinking rate to understand the
      pathophysiology of dry eye in thyroid eye disease (TED) patients. METHODS:
      Patients who were diagnosed with TED were enrolled between October 2015 and
      February 2016. Clinical measurements were performed in the following order: (i)
      external examination (Hertel exophthalmometer and palpebral fissure height), (ii)
      LipiView interferometer (lipid layer thickness [LLT], incomplete blinking rate,
      and meibography), (iii) slit-lamp biomicroscopy (corneal surface staining, tear
      breakup time, meibum expression, Marx line). RESULTS: Thirty eyes of 30 TED
      patients (male = 8; female = 22) were included in this study. The TED patient
      population had a mean age of 42.9 +/- 11.8 years and a mean clinical activity
      score (CAS) of 2.33 +/- 1.60. The meiboscore was 1.17 +/- 0.90 in the upper
      eyelid and 0.70 +/- 0.65 in the lower eyelid; scores were significantly higher in
      the upper eyelid (p < 0.001). The mean LLT was 82.43 +/- 24.52 nm, and the mean
      incomplete blinking rate was 51.04 +/- 33.62% (0-100%). CAS was the only variable
      that correlated with the meiboscore. There was no significant correlation between
      incomplete blinking and a degree of palpebral fissure height or proptosis.
      CONCLUSIONS: Tear film instability due to increased incomplete blinking can cause
      dry eye in TED. In addition to the increase in CAS, meibomian gland dysfunction
      may also be a cause of dry eye in TED. However, further comparative studies are
      needed to confirm these results.

PMID- 30119793
TI  - Resolution of recalcitrant chronic papillary conjunctivitis associated with
      epiphora following punctoplasty and lacrimal stenting.
AB  - OBJECTIVE: To assess the use of lacrimal stenting for chronic papillary
      conjunctivitis associated with epiphora in young adults with little or no atopic
      background. METHODS: A retrospective interventional case series of 21 consecutive
      patients (36 eyes) treated for epiphora and chronic papillary conjunctivitis at a
      tertiary university-affiliated medical center between January 2014 and August
      2015 by the same oculoplastic surgeon (I.A). Data were collected by retrospective
      file review. Patients with a history of ocular disease were excluded from the
      study. Treatment modalities included lacrimal stenting, punctoplasty, and
      conservative topical medication. The main outcome measure was post-treatment
      presence of epiphora and conjunctivitis. RESULTS: Mean patient age was 40 +/- 11
      years; 86% of patients were female. Fifteen (72%) had bilateral disease. Mean
      follow-up time was 3.9 +/- 1.7 months. Delayed tear clearance as well as a patent
      lacrimal apparatus were noted in all eyes. No apparent cause of the symptoms was
      found in any of the eyes. In 12 of the 13 patients (92%) who underwent tube or
      stent placement, the conjunctivitis and epiphora resolved. In the remainder,
      symptoms resolved bilaterally in only 1 of 4 patients (25%) who underwent
      punctoplasty and in only 1 of 4 patients (25%) treated conservatively.
      CONCLUSION: Recalcitrant papillary conjunctivitis improves following nasolacrimal
      stenting. Further studies are needed using a prospective controlled design and
      longer follow-up time.

PMID- 30119794
TI  - Comparison of exophthalmos measurements: Hertel exophthalmometer versus orbital
      parameters in 2-dimensional computed tomography.
AB  - OBJECTIVE: To compare the reliability of orbital parameters calculated using 2
      dimensional computed tomography (CT) and Hertel exophthalmometry when measuring
      exophthalmos in normal subjects and in patients with thyroid-associated
      orbitopathy (TAO). DESIGN: Retrospective, observational case series.
      PARTICIPANTS: CT images of 33 normal orbits and 69 orbits with TAO were included.
      METHODS: In central axial CT scans, globe area (GA), orbital area (OA), and GA/OA
      ratio were calculated by 2 observers using ImageJ. Interobserver agreement was
      analyzed for Hertel exophthalmometer and CT parameters. In patients with TAO, the
      association with activity and severity of TAO were also evaluated. RESULTS: GA
      and the GA/OA ratio measurements showed excellent interobserver agreement,
      whereas OA and the Hertel exophthalmometry measurements showed moderate agreement
      between the 2 observers. GA and the GA/OA ratio were significantly correlated
      with Hertel exophthalmometry measurements (r = -0.740, r = -0.706, respectively;
      all p < 0.001). GA and the GA/OA ratio were significantly correlated with the
      activity and severity of TAO (all p < 0.01). CONCLUSIONS: GA and the GA/OA ratio
      were reliable CT parameters with a high intraclass correlation coefficient
      compared with Hertel exophthalmometer.

PMID- 30119795
TI  - Progressive loss of retinal blood vessels in a live model of retinitis
      pigmentosa.
AB  - OBJECTIVE: To assess retinal blood vessels in a live retinitis pigmentosa (RP)
      model with rd1 mutation and green fluorescent protein (GFP) expressed in vascular
      endothelium. METHODS: Homozygous (hm) Tie2-GFP mice with rd1 mutation and known
      retinal degeneration were crossed with wild-type CD1 mice to generate control
      heterozygous (ht) Tie2-GFP mice. The retinas of 16 live hm mice were evaluated at
      2 weeks and 3, 5, and 8 months of age, and compared with age-matched control ht
      and CD1 mice by optical coherence tomography (OCT) and confocal scanning laser
      ophthalmoscopy (cSLO). Fluorescence intensity was measured and compared between
      strains at 3, 5, and 8 months. In vivo findings were validated by immunostaining
      with collagen IV and isolectin histopathology. RESULTS: All hm Tie2-GFP mice
      showed progressive outer retinal degeneration by OCT. Loss of small branches of
      blood vessels and then larger main vessels was seen by cSLO. Retinal tissue and
      vessels were preserved in control ht mice. At all ages, measurements of
      fluorescence intensity were reduced in hm compared with ht mice (p < 0.001). In
      all strains, intensity at 8 months was reduced compared with 3 months (p < 0.001)
      and 5 months (p = 0.021). Histopathological studies confirmed in vivo findings
      and revealed a pattern of blood vessel regression in the deep plexus, followed by
      intermediate and superficial retinal plexuses. CONCLUSIONS: This is the first
      evidence of progressive loss of retinal blood vessels in a live mouse model of
      RP. These findings may be highly relevant to understanding retinal degeneration
      in RP to prevent blindness.

PMID- 30119796
TI  - Vitrectomy in the management of diabetic macular edema in treatment-naive
      patients.
AB  - OBJECTIVE: To determine the efficacy of vitrectomy in eyes with treatment-naive
      diabetic macular edema (DME). METHODS: Consecutive patients with treatment-naive
      DME who underwent pars plana vitrectomy with internal limiting membrane peeling
      at a single institution were identified from the electronic medical records.
      Morphologic and visual acuity changes from baseline were analyzed at both the
      primary temporal endpoint (6 months) and the final examination with the
      investigators. The primary outcome measures included changes in best-corrected
      visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: Forty-four
      eyes of 44 patients were included in this retrospective study. The mean BCVA
      improved significantly from baseline until the 6-month primary endpoint (1.35
      logMAR vs 0.83 logMAR, p < 0.001) and stabilized through the final examination
      (0.77 logMAR). The BCVA improved by at least 0.1, 0.3, and 0.6 logMAR in 26
      (60%), 24 (55%), and 14 (32%) of eyes, respectively, whereas it worsened by 0.3
      logMAR in only 1 (2%) eye. Final BCVA correlated inversely with duration of
      diabetes (p = 0.01), presence of an epiretinal membrane (p = 0.02), and initial
      visual acuity (p = 0.03). Mean CRT decreased significantly from baseline through
      6 months (595 um vs 266 um; p < 0.001), and edema recurred in only 3 eyes (6%),
      one of which was subsequently treated with intravitreal bevacizumab. CONCLUSIONS:
      Pars plana vitrectomy significantly improves macular edema and visual acuity in
      eyes with treatment-naive DME. Prospective randomized trials are needed to better
      determine the efficacy of early vitrectomy.

PMID- 30119797
TI  - Surgical management of submacular hemorrhage: experience at an academic Canadian
      centre.
AB  - OBJECTIVE: To report the anatomical and visual outcomes of patients with thick
      submacular hemorrhage (SMH) treated with pars plana vitrectomy (PPV), subretinal
      tissue plasminogen activator (t-PA), and pneumatic displacement. DESIGN: Single
      centre, retrospective case series. PARTICIPANTS: A total of 99 eyes of 99
      consecutive patients with thick SMH secondary to any underlying etiology treated
      with PPV with subretinal t-PA and pneumatic displacement by 6 vitreoretinal
      surgeons at St. Michael's Hospital, Toronto, between July 2004 and August 2016.
      METHODS: All medical records and colour fundus photographs were reviewed for data
      collection. Blood displacement was evaluated at follow-up visits and classified
      as complete, partial, or none. Main outcome measures included blood displacement
      at final follow-up, postoperative Snellen best-corrected visual acuities (BCVA),
      and complication and recurrence rates. RESULTS: Patients had a mean age of 77.7
      +/- 12.3 years and were followed up for an average of 18.4 +/- 22.3 months. Wet
      age-related macular degeneration was the most common etiology associated with
      thick SMH (80.8%). Complete blood displacement was observed by final follow-up in
      85.9% of the cases, partial displacement in 12.1%, and none in 2.0%. Mean logMAR
      BCVA improved from 2.03 +/- 0.81 (Snellen 20/2143) at baseline to 1.80 +/- 1.00
      (Snellen 20/1262; p = 0.009) at final follow-up, and baseline BCVA was a
      significant predictor of final BCVA (p < 0.001). Early postoperative
      complications included vitreous hemorrhage in 13 eyes and rhegmatogenous retinal
      detachment in 8. Recurrent SMH was observed in 12 cases. CONCLUSIONS: Vitrectomy
      with subretinal t-PA and pneumatic displacement seems to be an effective
      treatment for SMH in terms of blood displacement and visual outcomes.

PMID- 30119798
TI  - Effect of glycosylated hemoglobin on response to ranibizumab therapy in diabetic
      macular edema: real-world outcomes in 312 patients.
AB  - OBJECTIVE: To investigate the effect of serum glycosylated hemoglobin (HbA1c) on
      the outcomes of ranibizumab therapy for diabetic macular edema (DME). DESIGN:
      Retrospective cohort study. PARTICIPANTS: Patients receiving ranibizumab
      injections for centre-involving DME in a National Health Service setting.
      METHODS: The Moorfields OpenEyes database was used to study eyes with DME treated
      with ranibizumab from October 2013 to November 2015 at the Moorfields City Road,
      Ealing, Northwick Park, and St George's Hospital sites. Only eyes receiving a
      minimum of 3 injections and completing 12 months of follow-up were included. If
      both eyes received treatment, the first eye treated was analyzed. When both eyes
      received initial treatment simultaneously, random number tables were used to
      select the eye for analysis. HbA1c was tested at the initiation of ranibizumab
      treatment. Multivariate regression analysis was used to identify relationships
      between HbA1c and the outcome measures. OUTCOMES: The primary outcome was change
      in visual acuity (VA) Early Treatment of Diabetic Retinopathy study (ETDRS)
      letters. The secondary outcomes were change in central subfield thickness (CSFT)
      and macular volume (MV), as well as number of injections in year 1. RESULTS:
      Three hundred and twelve eyes of 312 patients were included in the analysis.
      HbA1c was not related to change in VA (p = 0.577), change in CSFT (p = 0.099),
      change in MV (p = 0.082), or number of injections in year 1 (p = 0.859).
      CONCLUSIONS: HbA1c is not related to functional or anatomical outcomes at 1 year
      in DME treated with ranibizumab.

PMID- 30119799
TI  - Retinal thickness measurements in sickle cell patients with HbSS and HbSC
      genotype.
AB  - OBJECTIVE: Temporal macula thinning has been reported in sickle cell patients,
      but it remains unclear if there is a difference between HbSS and HbSC genotypes.
      We aimed to quantitatively compare macular thickness between eyes with HbSS and
      HbSC genotype. DESIGN: Retrospective descriptive study. METHODS: Consecutive
      patients seen over a 5.5-year period in the Ophthalmology Department at St
      Thomas' Hospital, London, were identified. Macular optical coherence tomography
      images were retrospectively analyzed. The retinal thickness in all 9 subfields of
      the Early Treatment Diabetic Retinopathy Study (ETDRS) grid was compared between
      HbSS and HbSC eyes. Right eyes and left eyes were analyzed independently, as well
      as averaged measurements from both eyes. Comparison was made between the 2
      genotypes, adjusting for age and sex, and for multiple testing. Scans were
      excluded in cases of poor fixation or ocular comorbidity affecting retinal
      thickness. RESULTS: 132 HbSC and 120 HbSS patients were identified. Scans from
      166 right and 153 left eyes were included (with approximately equal numbers of
      HbSS and HbSC genotypes). Mean retinal thickness was lower in HbSS eyes compared
      with HbSC eyes in all subfields of the ETDRS grid, but in most subfields the
      difference was <10 microns. Differences reached statistical significance for
      outer superior, inferior, and temporal subfields and the inner temporal subfield
      (p < 0.05). CONCLUSION: Although the HbSC genotype is more strongly associated
      with proliferative retinopathy, HbSS patients had on average more macular
      thinning.

PMID- 30119801
TI  - Gaussian thin system optics: revisited.

PMID- 30119800
TI  - Clinical features of infectious posterior segment uveitis.
AB  - OBJECTIVE: To assess the clinical findings and microbiology investigations in
      patients with suspected infectious posterior segment uveitis (PSU). DESIGN:
      Retrospective case study. METHODS: Between January and December 2014, medical
      records of 270 patients with PSU were reviewed. Baseline ocular examination,
      presumed and final diagnoses, microbiology investigations from aqueous or
      vitreous fluid, and peripheral blood were reviewed. RESULTS: Infectious PSU was
      suspected in 28 patients among 270 PSU cases (10.4%, 28/270), and 11 cases were
      of infectious origin (4.1%, 11/270). Six patients were immunocompromised: 5
      patients in the confirmed infectious PSU group (45.5%, 5/11) and 1 in the
      confirmed noninfectious group (5.9%, 1/17; p = 0.002). Initial visual acuity was
      1.8 +/- 0.35 logMAR and 0.9 +/- 0.23 logMAR for patients with confirmed
      infectious and noninfectious PSU, respectively (p = 0.04). Anterior chamber
      reaction was worse in patients with confirmed infectious PSU (1.8 +/- 0.49) than
      confirmed noninfectious cases (0.5 +/- 0.1; p = 0.003). The frequency of
      chorioretinitis among patients with confirmed infectious and noninfectious PSU is
      54.5% (6/11) and 11.8% (2/17; p = 0.03), respectively. Onset of confirmed
      infectious uveitis was more acute (<=6 weeks in duration) than noninfectious
      cases (p = 0.0015). Among the 11 patients with positive blood culture or
      serology, 6 had anterior and vitreous chamber fluid analysis. The rate of
      positive cultures and PCR is 16.7% (1/6) for aqueous humour and 50% (3/6) for
      vitreous samples. CONCLUSIONS: Clinical features more suggestive of infectious
      PSU include immunosuppression, worse initial visual acuity, acute onset, worse
      anterior chamber reaction, and chorioretinitis. Further studies are needed to
      enhance the diagnostic yields of aqueous and vitreous fluid analyses.

PMID- 30119803
TI  - Metastatic hepatocellular carcinoma mimicking acute dacryocystitis.

PMID- 30119802
TI  - Calcium crystals in the anterior chamber as a harbinger of hyperparathyroidism.

PMID- 30119804
TI  - Penetrating ocular injury by Western diamondback rattlesnake.

PMID- 30119805
TI  - Unilateral progressive myelinated retinal nerve fibres in an asymptomatic adult
      with optic nerve head drusen.

PMID- 30119806
TI  - Superior divisional oculomotor nerve palsy caused by fronto-ethmoidal sinusitis.

PMID- 30119807
TI  - A case of Hickam's dictum in a presenting third nerve palsy.

PMID- 30119808
TI  - New surgical option for optic nerve sheath meningiomas: fully endoscopic
      transnasal approach.

PMID- 30119809
TI  - Late dacryocystorhinostomy failure from lacrimal sump syndrome with pseudo-sac
      formation.

PMID- 30119810
TI  - Detection of plastic BBs on CT scanning of the orbit.

PMID- 30119811
TI  - Focal perifollicular mucinosis of the eyelid presenting as a benign nevus.

PMID- 30119812
TI  - Optic nerve giant cell astrocytoma in tuberous sclerosis complex.

PMID- 30119813
TI  - "Poppers Maculopathy": a case report and literature review.

PMID- 30119814
TI  - Hypotony secondary to perforation by scleral buckle.

PMID- 30119815
TI  - Atypical indocyanine green angiography findings after indocyanine green-assisted
      internal limiting membrane peeling.

PMID- 30119816
TI  - Central serous chorioretinopathy probably associated with isotretinoin in a
      keratoconus patient.

PMID- 30119817
TI  - Visual abstracts bring key message of venous and lymphatic research.

PMID- 30119818
TI  - Invited commentary.

PMID- 30119819
TI  - Invited commentary.

PMID- 30119820
TI  - Damage control of caval injuries in a porcine model using a retrievable Rescue
      stent.
AB  - OBJECTIVE: Early hemorrhage control before the operating room is essential to
      reduce the significant mortality associated with traumatic injuries of the vena
      cava. Conventional approaches present logistical challenges on the battlefield or
      in the trauma bay. A retrievable stent graft would allow rapid hemorrhage control
      in the preoperative setting when endovascular expertise is not immediately
      available and without committing a patient to the limitations of current
      permanent stents. This study details a refined retrievable Rescue stent for
      percutaneous delivery that was examined in a porcine survival model of
      penetrating caval hemorrhage. METHODS: A retrievable caval stent was reduced in
      delivery profile to a 9F sheath using finite element analysis. The final stent
      was constructed with a "petal and stem" design using nitinol wire followed by
      covering with polytetrafluoroethylene. Seven Yorkshire pigs (79-86 kg) underwent
      22F injury of the infrarenal vena cava with intentional class II hemorrhage (1200
      mL). Percutaneous deployment of the Rescue stent was used to temporize hemorrhage
      for 60 minutes, followed by resuscitation with cell saver blood and permanent
      caval repair. Hemorrhage control was documented with photography and angiography.
      Vital signs were recorded and laboratory values were measured out to 48 hours
      postoperatively. Data were examined with a repeated-measures analysis of
      variance. RESULTS: The profile of the caval Rescue stent was successfully reduced
      from 16F to 9F while remaining within fracture and shape memory limits for
      nitinol. In addition, both rapid deployment and recapture were preserved.
      Following intentional hemorrhage after caval injury, animals revealed a
      significant drop in mean arterial pressure (average, 30 mm Hg), acidosis, and
      elevated lactate level compared with before injury. Compared with uncontrolled
      hemorrhage, which resulted in death in <9 minutes, the Rescue stent achieved
      hemorrhage control in <1 minute after venous access in all seven animals. All
      animals were successfully recovered after permanent repair. There was no
      significant change in levels of transaminases, bilirubin, creatinine, or
      hemoglobin at 48 hours compared with preinjury baseline. CONCLUSIONS: A
      retrievable Rescue stent achieved rapid percutaneous hemorrhage control after a
      significant traumatic injury of the vena cava and allowed successful recovery of
      all injured animals. Further development of this approach may have utility in
      preoperative damage control of caval injuries.

PMID- 30119821
TI  - Regarding "An institution-wide algorithm for direct-stick embolization of
      peripheral venous malformations".

PMID- 30119822
TI  - Reply.

PMID- 30119823
TI  - Regarding "Outcomes of endovascular reconstruction of the inferior vena cava with
      self-expanding nitinol stents".

PMID- 30119824
TI  - Erratum to "Basic Properties of ATP-Induced Myosin Head Movement in Hydrated
      Myosin Filaments, Studied Using the Gas Environmental Chamber" [Micron 113 (2018)
      48-60].

PMID- 30119825
TI  - Fibroepithelioma of Pinkus: A Basal Cell Carcinoma With Distinctive Dermoscopic
      Features.

PMID- 30119826
TI  - There seem to be benefits from using local metformin as an adjuvant to scaling
      and root planing, but there is uncertainty about the magnitude.

PMID- 30119827
TI  - Evidence regarding how surgical treatment of actinic cheilitis compares with
      nonsurgical treatment is not trustworthy and does not consider all important
      outcomes.

PMID- 30119828
TI  - Silver diamine fluoride seems to be effective in preventing and arresting root
      caries in older adults compared with placebo, but there is very low certainty in
      the magnitude of the benefit.

PMID- 30119829
TI  - There seem to be no important differences in the effects of inferior alveolar
      nerve block and mental incisal nerve block when treating patients with
      irreversible pulpitis in mandibular premolars.

PMID- 30119830
TI  - [The CAR-T cells are here].
AB  - Due to immunotherapy, a new era of treatment is opening up for the treatment of
      solid cancers and hematological tumors. T cells genetically modified with a
      chimeric antigen receptor (CAR-T cells) have recently been proved efficient in
      hematological malignancies expressing CD19. On June 20th 2018, the European
      Medicines Agency gave a favorable opinion on two types of anti-CD19 CAR-T cells -
      tisagenlecleucel and axicabtagene ciloleucel - in the management of malignant
      hemopathies B after two lines of treatment. Their remarkable efficacy has been
      demonstrated in the first clinical trials conducted in the United States, but
      they present new and potentially serious side effects (cytokine release syndrome,
      neurotoxicity, among others). However, this new class of gene therapy raises
      practical problems regarding its production circuit, its delivery conditions and
      its high cost.

PMID- 30119831
TI  - Validity of Coronary Artery Disease Consortium Models for Predicting Obstructive
      Coronary Artery Disease & Cardiovascular Events in Patients with Acute Chest Pain
      Considered for Coronary Computed Tomographic Angiography.
AB  - Although the majority of acute chest pain patients are diagnosed with noncardiac
      chest pain after noninvasive testing, identifying these low-risk patients before
      testing is challenging. The objective of this study was to validate the coronary
      artery disease (CAD) consortium models for predicting obstructive CAD and 30-day
      major adverse cardiovascular events (MACE) in acute chest pain patients
      considered for coronary computed tomography angiogram, as well as to determine
      the pretest probability threshold that identifies low-risk patients with <1%
      MACE. We studied 1,981 patients with no known CAD and negative initial troponin
      and electrocardiogram. We evaluated CAD consortium models (basic: age, sex, and
      chest pain type; clinical: basic + diabetes, hypertension, dyslipidemia, and
      smoking; and clinical + coronary calcium score [CAC] models) for prediction of
      obstructive CAD (>=50% stenosis on coronary CT angiogram) and 30-day MACE (Acute
      Myocardial Infarction, revascularization, and mortality). The C-statistic for
      predicting obstructive CAD was 0.77 (95% confidence interval [CI] 0.73 to 0.77)
      for the basic, 0.80 (95% CI 0.77 to 0.80) for the clinical, and 0.88 (95% CI 0.85
      to 0.88) for the clinical + CAC models. The C-statistic for predicting 30-day
      MACE was 0.82 (95% CI 0.77 to 0.87) for the basic, 0.84 (95% CI 0.79 to 0.88) for
      the clinical, and 0.87 (95% CI 0.83 to 0.91) for the clinical + CAC models. In
      47.3% of patients for whom the clinical model predicted <=5% probability for
      obstructive CAD, the observed 30-day MACE was 0.53% (95% CI 0.07% to 0.999%); in
      the 66.9% of patients for whom the clinical + CAC model predicted <=5%
      probability, the 30-day MACE was 0.75% (95% CI 0.29% to 1.22%). We propose a
      chest pain evaluation algorithm based on these models that classify 63.3% of
      patients as low risk with 0.56% (95% CI 0.15% to 0.97%) 30-day MACE. In
      conclusion, CAD consortium models have excellent diagnostic and prognostic value
      for acute chest pain patients and can safely identify a significant proportion of
      low-risk patients by achieving <1% missed 30-day MACE.

PMID- 30119832
TI  - Telling Left from Right in Breathing Nucleosomes.

PMID- 30119833
TI  - Influence of Microscopic Interactions on the Flexible Mechanical Properties of
      Viral DNA.
AB  - During the packaging and ejection of viral DNA, its mechanical properties play an
      essential role in viral infection. Some of these mechanical properties originate
      from different microscopic interactions of the encapsulated DNA in the capsid.
      Based on an updated mesoscopic model of the interaction potential by Parsegian et
      al., an alternative continuum elastic model of the free energy of the confined
      DNA in the capsid is developed in this work. With this model, we not only
      quantitatively identify the respective contributions from hydration repulsion,
      electrostatic repulsion, entropy and elastic bending but also predict the ionic
      effect of viral DNA's mechanical properties during the packaging and ejection.
      The relevant predictions are quantitively or qualitatively consistent with the
      existing experimental results. Furthermore, the nonmonotonous or monotonous
      changes in the respective contributions of microscopic interactions to the
      ejection force and free energy at different ejection stages are revealed
      systematically. Among these, the nonmonotonicity in the entropic contribution
      implies a transition of viral DNA structure from order to disorder during the
      ejection.

PMID- 30119834
TI  - Redox-Driven Proton Pumps of the Respiratory Chain.
AB  - In aerobic cells, the proton gradient that drives ATP synthesis is created by
      three different proton pumps-membrane enzymes of the respiratory electron
      transport chain known as complex I, III, and IV. Despite the striking
      dissimilarity of structures and apparent differences in molecular mechanisms of
      proton pumping, all three enzymes have much in common and employ the same
      universal physical principles of converting redox energy to proton pumping. In
      this study, we describe a simple mathematical model that illustrates the general
      principles of redox-driven proton pumps and discuss their implementation in
      complex I, III, and IV of the respiratory chain.

PMID- 30119835
TI  - Mechanical Cues in Spinal Cord Injury.

PMID- 30119837
TI  - Clozapine-Associated Aspiration Pneumonia: Case Series and Review of the
      Literature: Reply.

PMID- 30119836
TI  - Modeling In Vivo Interstitial Hydration-Pressure Relationships in Skin and
      Skeletal Muscle.
AB  - A theoretical understanding of hydrostatic pressure-fluid volume relationships,
      or equations of state, of interstitial fluid in skin and skeletal muscle through
      mathematical/physical modeling is lacking. Here, we investigate at the
      microscopic level forces that seem to underlie and determine the movements of
      fluid and solid tissue elements on the microscopic as well as on the macroscopic
      level. Effects that occur during variation of hydration due to interaction
      between expanding glycosaminoglycans (GAGs) and the collagen interstitial matrix
      of tissue seem to be of major importance. We focus on these interactions that let
      effects from spherical GAGs expand and contract relative to collagen on the
      microscopic level as hydration changes and thereby generate a hydration-dependent
      electrostatic pressure on the extracellular matrix on the microscopic level. This
      pressure spreads to macroscopic levels and become a key factor for setting up
      equations of state for skin and skeletal muscle interstitia. The modeling for a
      combined skeletal muscle and skin tissue is one dimensional, i.e., a flat box
      that may mimic central transverse parts of tissue with more complex geometry.
      Incorporating values of GAG and collagen densities and fluid contents of skin and
      muscle tissues that are of an order of magnitude found in literature into the
      model gives interstitial hydrostatic pressure- fluid volume relationships for
      these tissues that agree well with experimental results.

PMID- 30119838
TI  - Tardive Dyskinesia Suppression Seen During Catatonic State: A Case Report.

PMID- 30119839
TI  - Reinitiation of Electroconvulsive Therapy 4 Weeks After the Diagnosis of ECT
      Induced Takotsubo Cardiomyopathy.

PMID- 30119840
TI  - The Neuroanatomy of Somatoform Disorders: A Magnetic Resonance Imaging Study.
AB  - BACKGROUND: Somatoform Disorders (SD) are a heterogeneous group of psychiatric
      syndromes characterized by common symptoms, which may mimic a physical condition
      but they are not explained by a medical condition. Although the biologic nature
      of this disorder has been widely accepted, the neuroanatomical correlates
      characterizing SD are still inconclusive. Therefore, this study aims to explore
      gray matter (GM) volume alterations in SD patients compared to healthy controls
      and their possible association with clinical and cognitive measures. METHOD: We
      used voxel-based morphometry to examine regional GM volumes in 20 inpatients with
      SD and 24-matched healthy controls. Only for SD patients, we employed multiple
      instruments to assess psychopathology and cognitive functioning, which were then
      used to explore their association with GM volume deficits. RESULTS: Compared to
      healthy controls, SD patients showed GM volume reductions in hypothalamus, left
      fusiform gyrus, right cuneus, left inferior frontal gyrus, left posterior
      cingulate, and right amygdala (p < 0.05, cluster Family Wise Error corrected).
      Additionally, in SD, Symptom Checklist-90-Phobia and Hamilton Depressive Rating
      Scale scores negatively correlated with specific fronto-temporoparietal regions
      whereas Symptom Checklist-90-Sleep scores positively correlated with anterior
      cingulate cortex. Lastly, the Boston Naming Test negatively correlated with
      fronto-temporoparietal and striatal volumes whereas Free and Cued Selective
      Reminding Test and Stroop scores positively correlated with superior temporal
      gyrus and cuneus, respectively (all p < 0.05, cluster Family Wise Error
      corrected). CONCLUSION: Our results suggest that SD might be characterized by
      selective impairments in specific cortico-limbic regions associated to two
      overlapping circuits, the neuromatrix of pain and the emotion regulation system.

PMID- 30119841
TI  - Intracoronal stress transfer through enamel following RBC photopolymerisation: A
      synchrotron X-ray study.
AB  - OBJECTIVES: To measure the spatial distribution of crystallographic strain in
      tooth enamel induced by the photo-polymerisation of a dimethacrylate resin based
      composite cavity restoration. METHODS: Six sound first premolar teeth, allocated
      into two groups (n=3), were prepared with mesio-occlusal distal cavities. The
      enamel was machined at the point of maximum convexity on the outer tooth to
      create a vertical fin of thickness 100MUm and 0.5mm depth to allow for
      synchrotron X-ray diffraction measurements. 2D diffraction patterns were used to
      determine crystallite orientation and quantify changes in the hydroxyapatite
      crystal lattice parameters, before and after photo-polymerisation of a composite
      material placed in the cavity, to calculate strain in the respective axis. The
      composite was photo-polymerised with either relatively high (1200mWcm-2, group 1)
      or low (480mWcm-2, group 2) irradiances using LED or quartz halogen light
      sources, respectively. A paired t-test was used to determine significant
      differences in strain between irradiance protocols at alpha=0.001. RESULTS: Photo
      polymerisation of the composite in the adjacent cavity induced significant
      changes in both the crystallographic c and a axes of the enamel measurement area.
      However the magnitude of strain was low with ~0.1% difference before and after
      composite photo-polymerisation. Strain in enamel was not uniformly distributed
      and varied spatially as a function of crystallite orientation. Increased
      alignment of crystallites perpendicular to the cavity wall was associated with
      higher c axis strain. Additionally, strain was significantly greater in the c
      (p<0.001) and a axis (p<0.001) when using a high irradiance photo-polymerisation
      protocol. SIGNIFICANCE: Although cuspal deflection is routinely measured to
      indirectly assess the 'global' effect of composite shrinkage on the tooth
      restoration complex, here we show that absolute strains generated in enamel are
      low, indicating strain relief mechanisms may be operative. The use of low
      irradiance protocols for photo-polymerisation resulted in reduced strain.

PMID- 30119842
TI  - Engineering intelligent particle-lipid composites that control lipase-mediated
      digestion.
AB  - Nanostructured particle-lipid composites have emerged as state-of-the-art carrier
      systems for poorly water-soluble bioactive molecules due to their ability to
      control and enhance the lipase-mediated hydrolysis of encapsulated triglycerides,
      leading to a subsequent improvement in the solubilisation and absorption of
      encapsulated species. The first generation of particle-lipid composites (i.e.
      silica-lipid hybrid (SLH) microparticles) were designed and fabricated by spray
      drying a silica nanoparticle-stabilised Pickering emulsion, to create a novel
      three-dimensional architecture, whereby lipid droplets were encapsulated within a
      porous matrix support. The development of SLH microparticles has acted as a solid
      foundation for the synthesis of several next generation particle-lipid
      composites, including polymer-lipid hybrid (PLH) and clay-lipid hybrid systems
      (CLH), which present lipase with unique lipid microenvironments for optimised
      lipolysis. This review details the methods utilised to engineer lipid hybrid
      particles and the strategic investigations that have been performed to determine
      the influence of key material characteristics on digestion enzyme activity. In
      doing so, this provides insight into manipulating the mechanism of lipase action
      through the intelligent design of lipid-based biomaterials for their use in drug
      delivery formulations and novel functional foods.

PMID- 30119843
TI  - Predictors of survival and favorable neurological outcome in patients treated
      with targeted temperature management after cardiac arrest: A systematic review
      and meta-analysis.
AB  - This study was aimed at a serial evaluation of the prognostic values of initial
      shockable rhythm, bystander cardiopulmonary resuscitation (CPR) and gender for
      neurological outcome and survival in adults treated with targeted temperature
      management (TTM) following cardiac arrest (CA). PubMed, Embase and the Cochrane
      Library were searched for eligible studies. Pooled odds ratio (OR) with 95%
      confidence intervals (CIs) was calculated to evaluate prognostic values using
      RevMan 5.3. The outcomes were favorable neurological outcome (defined as cerebral
      performance category of 1 and 2) and survival. Seventeen studies were subjected
      to the meta-analysis. Favorable neurological outcome was associated with
      significantly higher odds of an initial shockable rhythm (OR: 7.63, 95%CI: 6.51
      8.96), bystander CPR (OR: 1.44, 95%CI: 1.14-1.82), male (OR: 1.39, 95%CI: 1.20
      1.61). Survival was associated with higher odds of an initial shockable rhythm
      (OR: 4.88, 95%CI: 3.18-4.79), higher odds of bystander CPR (OR: 1.71, 95%CI: 1.05
      2.77). No significant association was found between survival and male. In adult
      patients treated with TTM, initial shockable rhythm, bystander CPR and male sex
      were associated with a higher likelihood of favorable neurological outcome.
      Initial shockable rhythm and bystander CPR were associated with a higher
      likelihood of survival. These factors could help in identifying patients who are
      eligible for TTM.

PMID- 30119844
TI  - Radiomics based detection and characterization of suspicious lesions on full
      field digital mammograms.
AB  - BACKGROUND AND OBJECTIVE: Early detection is the important key to reduce breast
      cancer mortality rate. Detecting the mammographic abnormality as a subtle sign of
      breast cancer is essential for the proper diagnosis and treatment. The aim of
      this preliminary study is to develop algorithms which detect suspicious lesions
      and characterize them to reduce the diagnostic errors regarding false positives
      and false negatives. METHODS: The proposed hybrid mechanism detects suspicious
      lesions automatically using connected component labeling and adaptive fuzzy
      region growing algorithm. A novel neighboring pixel selection algorithm reduces
      the computational complexity of the seeded region growing algorithm used to
      finalize lesion contours. These lesions are characterized using radiomic features
      and then classified as benign mass or malignant tumor using k-NN and SVM
      classifiers. Two datasets of 460 full field digital mammograms (FFDM) utilized in
      this clinical study consists of 210 images with malignant tumors, 30 with benign
      masses and 220 normal breast images that are validated by radiologists expert in
      mammography. RESULTS: The qualitative assessment of segmentation results by the
      expert radiologists shows 91.67% sensitivity and 58.33% specificity. The effects
      of seven geometric and 48 textural features on classification accuracy, false
      positives per image (FPsI), sensitivity and specificity are studied separately
      and together. The features together achieved the sensitivity of 84.44% and
      85.56%, specificity of 91.11% and 91.67% with FPsI of 0.54 and 0.55 using k-NN
      and SVM classifiers respectively on local dataset. CONCLUSIONS: The overall
      breast cancer detection performance of proposed scheme after combining geometric
      and textural features with both classifiers is improved in terms of sensitivity,
      specificity, and FPsI.

PMID- 30119845
TI  - Fuzzy decision support systems to diagnose musculoskeletal disorders: A
      systematic literature review.
AB  - BACKGROUND AND OBJECTIVE: Musculoskeletal disorders (MSDs) are one of the most
      important causes of disability with a high prevalence. The accurate and timely
      diagnosis of these disorders is often difficult. Clinical decision support
      systems (CDSSs) can help physicians to diagnose diseases quickly and accurately.
      Given the ambiguous nature of MSDs, fuzzy logic can be helpful in designing the
      CDSSs knowledge bases. The present study aimed to review the studies on fuzzy
      CDSSs to diagnose MSDs. METHODS: A comprehensive search was conducted in Medline,
      Scopus, Cochrane Library, and ISI Web of Science databases to identify relevant
      studies published until March 15, 2016. Studies were included in which CDSSs were
      developed using fuzzy logic to diagnose MSDs, and tested their accuracy using
      real data from patients. RESULTS: Of the 3188 papers examined, 23 papers included
      according to the inclusion criteria. The results showed that among all the
      designed CDSSs only one (CADIAG-2) was implemented in the clinical environment.
      In about half of the included studies (52%), CDSSs were designed to diagnose
      inflammatory/infectious disorder of the bone and joint. In most of the included
      studies (70%), the knowledge was extracted using a combination of three methods
      (acquiring from experts, analyzing the data, and reviewing the literature). The
      median accuracy of fuzzy rule-based CDSSs was 91% and it was 90% for other fuzzy
      models. The most frequently used membership functions were triangular and
      trapezoidal functions, and the most used method for inference was the Mamdani.
      CONCLUSIONS: In general, fuzzy CDSSs have a high accuracy to diagnose MSDs.
      Despite the high accuracy, these systems have been used to a limited extent in
      the clinical environments. To design of knowledge base for CDSSs to diagnose
      MSDs, rule-based methods are used more than other fuzzy methods.

PMID- 30119846
TI  - Magnetohydrodynamic blood flow in patients with coronary artery disease.
AB  - OBJECTIVES: We aim to investigate the effect of a magnetic field with varying
      intensities on haemodynamic perturbations in a cohort of patients with coronary
      artery disease. METHODS: Transient computational fluid dynamics (CFD) simulations
      were performed in three-dimensional (3D) models of coronary arteries
      reconstructed from 3D quantitative coronary angiography. The effect of magnetic
      field on wall shear stress (WSS) derived parameters including maximum wall shear
      stress (MWSS) and size of regions with low wall shear stress (ALWSS) as well as
      length of flow recirculation zones were determined. RESULTS: The results showed a
      substantial reduction in MWSS, ALWSS and length of flow recirculation zones in
      the presence of magnetic field, in particular for coronaries with moderate to
      severe stenoses. When the whole cohort examined, time-averaged wall shear stress
      (TAWSS), ALWSS and the length of flow recirculation zones in the absence of
      magnetic field were approximately 1.71, 4.69 and 8.46 times greater than those in
      the presence of magnetic field, respectively. CONCLUSION: Our findings imply that
      an externally applied magnetic field can improve haemodynamic perturbations in
      human coronary arteries.

PMID- 30119847
TI  - Hybrid constraint optimization for 3D subcutaneous vein reconstruction by near
      infrared images.
AB  - BACKGROUND AND OBJECTIVE: The development of biometric identification technology
      and intelligent medication has enabled researchers to analyze subcutaneous veins
      from near-infrared images. However, the stereo reconstruction of subcutaneous
      veins has not been well studied, and the results are difficult to utilize in
      clinical practice. METHODS: We present a hybrid constraint optimization (HCO)
      matching algorithm for vein reconstruction to solve the matching failure problems
      caused by the incomplete segmentation of vein structures captured from different
      views. This algorithm initially introduces the existence of the epipolar and
      homography constraints in the subcutaneous vein matching. Then, the HCO matching
      algorithm of the vascular centerline is established by homography point-to-point
      matching, homography matrix optimization, and vascular section matching. Finally,
      the 3D subcutaneous vein is reconstructed on the basis of the principle of
      triangulation and system calibration parameters. RESULTS: To validate the
      performance of the proposed matching method, we designed a series of experiments
      to evaluate the effectiveness of the hybrid constraint optimization method. The
      experiments were performed on simulated and real datasets. 42 real vascular
      images were analyzed on the basis of different matching strategies. Experimental
      result shows that the matching accuracy increased significantly with the proposed
      optimization matching method. To calculate the reconstruction accuracy, we
      reconstructed seven simulated cardboards and measured 10 vascular distances in
      each simulated cardboard. The average vascular distance error of each simulated
      image was within 1.0 mm, and the distance errors of 75% feature points were less
      than 1.5 mm. Also, we printed a 3D simulated vein model to improve the
      illustration of this system. The reconstruction error extends from -3.58 mm to
      1.94 mm with a standard deviation of 0.68 mm and a mean of 0.07 mm. CONCLUSIONS:
      The algorithm is validated in terms of homography optimization, matching
      efficiency, and simulated vascular reconstruction error. The experimental results
      demonstrate that the veins captured from the left and right views can be
      accurately matched through the proposed algorithm.

PMID- 30119848
TI  - Estimating the refractive index of oxygenated and deoxygenated hemoglobin using
      genetic algorithm - support vector regression model.
AB  - BACKGROUND AND OBJECTIVES: The refractive index of hemoglobin plays important
      role in hematology due to its strong correlation with the pathophysiology of
      different diseases. Measurement of the real part of the refractive index remains
      a challenge due to strong absorption of the hemoglobin especially at relevant
      high physiological concentrations. So far, only a few studies on direct
      measurement of refractive index have been reported and there are no firm
      agreements on the reported values of refractive index of hemoglobin due to
      measurement artifacts. In addition, it is time consuming, laborious and expensive
      to perform several experiments to obtain the refractive index of hemoglobin. In
      this work, we proposed a very rapid and accurate computational intelligent
      approach using Genetic Algorithm/Support Vector Regression models to estimate the
      real part of the refractive index for oxygenated and deoxygenated hemoglobin
      samples. METHODS: These models utilized experimental data of wavelengths and
      hemoglobin concentrations in building highly accurate Genetic Algorithm/Support
      Vector Regression model (GA-SVR). RESULTS: The developed methodology showed high
      accuracy as indicated by the low root mean square error values of 4.65 * 10-4 and
      4.62 * 10-4 for oxygenated and deoxygenated hemoglobin, respectively. In
      addition, the models exhibited 99.85 and 99.84% correlation coefficients (r) for
      the oxygenated and deoxygenated hemoglobin, thus, validating the strong agreement
      between the predicted and the experimental results CONCLUSIONS: Due to the
      accuracy and relative simplicity of the proposed models, we envisage that these
      models would serve as important references for future studies on optical
      properties of blood.

PMID- 30119849
TI  - Melanoma recognition in dermoscopy images using lesion's peripheral region
      information.
AB  - BACKGROUND AND OBJECTIVES: Melanoma is one of the most dangerous forms of skin
      cancer, but it has a high survival rate if diagnosed on time. The first
      diagnostic approach in melanoma recognition is to visually assess the lesion
      through dermoscopic images. Computer-aided diagnosis systems for melanoma
      recognition has attracted a lot of attention in the last decade and proved to be
      helpful in that area. Methods for skin lesions analysis usually involves three
      main steps: lesion segmentation, feature extraction, and features classification.
      Extracting highly discriminative features from the lesion has a great impact on
      the recognition task. In this paper, we are seeking a lesion recognition system
      that incorporates these highly discriminative features. METHODS: For segmentation
      step, we use contour propagation model with a novel two-component speed function.
      In the feature extraction step, a new set of features based on peripheral
      information of the lesion are introduced. For this end, the peripheral area of
      the lesion is mapped to log-polar space using the Daugman's transformation and
      then a set of texture features are extracted from it. Newly introduced features
      do not need further segmentation of dermoscopic structures and are robust against
      lesion's scale, orientation, location, and shape variation. We also design the
      other global texture features to describe only the information from the lesion
      area. In the classification step, we evaluated two different schemes to prove the
      distinction power of the new features, one comprises linear SVM to recognize
      melanoma vs. nevus and the other scheme uses RUSBoost classifier to recognize
      melanoma vs. nevus and atypical-nevus. Sequential feature selection algorithm has
      been utilized in each classification scheme to rank features based on their
      distinction power. RESULTS: Cross-validation experiments on the well-known PH2
      dataset resulted in an average of 97% for sensitivity and 100% for specificity on
      melanoma vs. nevus recognition task using only four features. Also, in the second
      classification scheme, we achieved high sensitivity and specificity values of 95%
      for melanoma vs. nevus and atypical nevus recognition experiments. CONCLUSION:
      High values for evaluation metrics show that the proposed melanoma recognition
      system is superior to the other state-of-the-art algorithms, which proves the
      high distinction power of the newly introduced features.

PMID- 30119851
TI  - Robust heartbeat detection using multimodal recordings and ECG quality assessment
      with signal amplitudes dispersion.
AB  - BACKGROUND AND OBJECTIVES: The electrocardiogram (ECG) is a bioelectric signal
      which represents heart's electrical activity graphically. This bioelectric signal
      is subject of lots of researches and so many algorithms are designed for
      extracting lots of clinically important parameters from it. Most of these
      parameters can be measured by detecting R peak of the QRS complex in ECG signal,
      but when ECG signal is corrupted by different kinds of noise and artifacts, such
      as electromyogram (EMG) from muscles, power line interference, motion artifacts
      and changes in electrode-skin interface, detection of R peaks becomes hard or
      impossible for algorithms which are designed for heart beat detection on ECG
      signal. In modern patient monitoring devices often not only one ECG signal is
      recorded but also so many other biological signals are simultaneously recorded
      from the patient which some of them, such as blood pressure (BP), are containing
      useful information about the heart activity which could be very helpful in making
      the heart beat detection more robust. METHODS: In this study, a new method is
      introduced for distinguishing noise free segments of ECG from noisy segments that
      uses samples amplitudes dispersion with an adaptive threshold for variance of
      samples amplitude and a method which uses compatibility of detected beats in ECG
      and some of other signals which are related to the heart activity such as BP,
      arterial pressure (ART) and pulmonary artery pressure (PAP). A prioritization is
      applied in other pulsatile signals based on the amplitude and clarity of peaks on
      them, and a fusion strategy is employed for segments on which ECG is noisy and
      other available signals in the data, which contain peaks corresponding to R peak
      of the ECG, are scored in a three steps scoring function. RESULTS: The final
      scores achieved by the proposed algorithm in terms of average sensitivity,
      positive predictive value, accuracy and F1 measure on the database which is
      freely available in Physionet Computing in Cardiology Challenge 2014 are
      respectively 95.47%, 96.03%, 93.11% and 95.62%. CONCLUSIONS: The results show the
      outperformance of the proposed method against other recently published works.

PMID- 30119852
TI  - A novel integrated action crossing method for drug-drug interaction prediction in
      non-communicable diseases.
AB  - BACKGROUND AND OBJECTIVE: Drug-drug interaction (DDI) is one of the main causes
      of toxicity and treatment inefficacy. This work focuses on non-communicable
      diseases (NCDs), the non-transmissible and long-lasting diseases since they are
      the leading cause of death globally. Drugs that are used in NCDs increase the
      probability of DDIs as a result of long time usage. This work proposes an
      Integrated Action Crossing (IAC) method that is effective in predicting the NCDs
      DDIs based on pharmacokinetic (PK) mechanism. METHODS: Drug-Enzyme (CYP450) and
      Drug-Transporter actions including substrate, inhibitor and inducer affect the PK
      mechanism of other drugs. Hence, this paper proposes an enzyme and transporter
      protein integrated action crossing method for DDIs prediction in NCDs. The NCDs
      Drugs information was retrieved from the DrugBank database and the actions of
      enzymes and transporter proteins that were crossed and integrated. The datasets
      were generated for machine training. RESULTS: Three machine learning approaches:
      Support Vector Machine, k-Nearest Neighbors, and Neural Networks were used for
      the assessment of the method. Performance evaluation was performed through five
      fold cross validation and the different datasets and learning methods were
      compared. Two layers NNs achieved the best performance at the accuracy of 83.15%
      (F-Measure 85.23% and AUC 0.901). CONCLUSIONS: The IAC method delivers better
      performance compared to the conventional method for the identification of NCDs
      DDIs.

PMID- 30119850
TI  - State-of-the-art review on automated lumen and adventitial border delineation and
      its measurements in carotid ultrasound.
AB  - BACKGROUND AND OBJECTIVE: Accurate, reliable, efficient, and precise measurements
      of the lumen geometry of the common carotid artery (CCA) are important for (a)
      managing the progression/regression of atherosclerotic build-up and (b) the risk
      of stroke. The image-based degree of stenosis in the carotid artery and the
      plaque burden can be predicted using the automated carotid lumen diameter
      (LD)/inter-adventitial diameter (IAD) measurements from B-mode ultrasound images.
      The objective of this review is to present the state-of-the-art methods and
      systems for the measurement of LD/IAD in CCA based on automated or semi-automated
      strategies. Further, the performance of these systems is compared based on
      various metrics for its measurements. METHODS: The automated algorithms proposed
      for the segmentation of carotid lumen are broadly classified into two different
      categories as: region-based and boundary-based. These techniques are discussed in
      detail specifying their pros and cons. Further, we discuss the challenges
      encountered in the segmentation process along with its quantitative assessment.
      Lastly, we present stenosis quantification and risk stratification strategies.
      RESULTS: Even though, we have found more boundary-based approaches compared to
      region-based approaches in the literature, however, the region-based strategy
      yield more satisfactory performance. Novel risk stratification strategies are
      presented. On a patient database containing 203 patients, 9 patients are
      identified as high risk patients, whereas 27 patients are identified as medium
      risk patients. CONCLUSIONS: We have presented different techniques for the lumen
      segmentation of the common carotid artery from B-mode ultrasound images and
      measurement of lumen diameter and inter-adventitial diameter. We believe that the
      issue regarding boundary-based techniques can be compensated by taking regional
      statistics embedded with boundary-based information.

PMID- 30119853
TI  - A new deformable model based on fractional Wright energy function for tumor
      segmentation of volumetric brain MRI scans.
AB  - BACKGROUND AND OBJECTIVES: The MRI brain tumors segmentation is challenging due
      to variations in terms of size, shape, location and features' intensity of the
      tumor. Active contour has been applied in MRI scan image segmentation due to its
      ability to produce regions with boundaries. The main difficulty that encounters
      the active contour segmentation is the boundary tracking which is controlled by
      minimization of energy function for segmentation. Hence, this study proposes a
      novel fractional Wright function (FWF) as a minimization of energy technique to
      improve the performance of active contour without edge method. METHOD: In this
      study, we implement FWF as an energy minimization function to replace the
      standard gradient-descent method as minimization function in Chan-Vese
      segmentation technique. The proposed FWF is used to find the boundaries of an
      object by controlling the inside and outside values of the contour. In this
      study, the objective evaluation is used to distinguish the differences between
      the processed segmented images and ground truth using a set of statistical
      parameters; true positive, true negative, false positive, and false negative.
      RESULTS: The FWF as a minimization of energy was successfully implemented on
      BRATS 2013 image dataset. The achieved overall average sensitivity score of the
      brain tumors segmentation was 94.8 +/- 4.7%. CONCLUSIONS: The results demonstrate
      that the proposed FWF method minimized the energy function more than the gradient
      decent method that was used in the original three-dimensional active contour
      without edge (3DACWE) method.

PMID- 30119854
TI  - A hackathon promoting Taiwanese health-IoT innovation.

PMID- 30119856
TI  - Using machine-learning approaches to predict non-participation in a nationwide
      general health check-up scheme.
AB  - BACKGROUND: In the time since the launch of a nationwide general health check-up
      and instruction program in Japan in 2008, interest in the formulation of an
      effective and efficient strategy to improve the participation rate has been
      growing. The aim of this study was to develop and evaluate models identifying
      those who are unlikely to undergo general health check-ups. We used machine
      learning methods to select interventional targets more efficiently. METHODS: We
      used information from a local government database of Japan. The study population
      included 7290 individuals aged 40-74 years who underwent at least one general
      health check-up between 2012 and 2015. We developed four predictive models based
      on the extreme gradient boosting (XGBoost), random forest (RF), support vector
      machines (SVMs), and logistic regression (LR) algorithms, using machine-learning
      techniques, and compared the areas under the curves (AUCs) of the models with
      those of the heuristic method (which presumes that the individuals who underwent
      a general health check-up in the previous year will do so again in the following
      year). RESULTS: The AUCs for the XGBoost, RF, SVMs, LR, and heuristic
      models/method were 0.829 (95% confidence interval [CI]: 0.806-0.853), 0.821 (95%
      CI: 0.797-0.845), 0.812 (95% CI: 0.787-0.837), 0.816 (95% CI: 0.791-0.841), and
      0.683 (95% CI: 0.657-0.708), respectively. XGBoost model exhibited the best AUC,
      and the performance was significantly better than that of SVMs (p = 0.034), LR (p
      = 0.017), and heuristic method (p < 0.001). However, the performance of XGBoost
      did not differ significantly from that of RF (p = 0.229). CONCLUSION: Predictive
      models using machine-learning techniques outperformed the existing heuristic
      method when used to predict participation in a general health check-up system by
      eligible participants.

PMID- 30119855
TI  - Classification of lung cancer subtypes based on autofluorescence bronchoscopic
      pattern recognition: A preliminary study.
AB  - BACKGROUND AND OBJECTIVES: Lung cancer is the leading cause of cancer deaths
      worldwide. With current use of autofluorescent bronchoscopic imaging to detect
      early lung cancer and limitations of pathologic examinations, a computer-aided
      diagnosis (CAD) system based on autofluorescent bronchoscopy was proposed to
      distinguish different pathological cancer types to achieve objective and
      consistent diagnoses. METHODS: The collected database consisted of 12
      adenocarcinomas and 11 squamous cell carcinomas. The corresponding
      autofluorescent bronchoscopic images were first transformed to a hue (H),
      saturation (S), and value (V) color space to obtain better interpretation of the
      color information. Color textural features were respectively extracted from the
      H, S, and V channels and combined in a logistic regression classifier to classify
      malignant types by machine learning. RESULTS: After feature selection, the
      proposed CAD system achieved an accuracy of 83% (19/23), a sensitivity of 73%
      (8/11), a specificity of 92% (11/12), a positive predictive value of 89% (8/9), a
      negative predictive value of 79% (11/14), and an area under the receiver
      operating characteristic curve of 0.81 for distinguishing lung cancer types.
      CONCLUSIONS: The proposed CAD system based on color textures of autofluorescent
      bronchoscopic images provides a diagnostic method of malignant types in clinical
      use.

PMID- 30119857
TI  - Automatic macular edema identification and characterization using OCT images.
AB  - BACKGROUND AND OBJECTIVE: The detection and characterization of the intraretinal
      fluid accumulation constitutes a crucial ophthalmological issue as it provides
      useful information for the identification and diagnosis of the different types of
      Macular Edema (ME). These types are clinically defined, according to the clinical
      guidelines, as: Serous Retinal Detachment (SRD), Diffuse Retinal Thickening (DRT)
      and Cystoid Macular Edema (CME). Their accurate identification and
      characterization facilitate the diagnostic process, determining the disease
      severity and, therefore, allowing the clinicians to achieve more precise analysis
      and suitable treatments. METHODS: This paper proposes a new fully automatic
      system for the identification and characterization of the three types of ME using
      Optical Coherence Tomography (OCT) images. In the case of SRD and CME edemas,
      multilevel image thresholding approaches were designed and combined with the
      application of ad-hoc clinical restrictions. The case of DRT edemas, given their
      complexity and fuzzy regional appearance, was approached by a learning strategy
      that exploits intensity, texture and clinical-based information to identify their
      presence. RESULTS: The system provided satisfactory results with F-Measures of
      87.54% and 91.99% for the DRT and CME detections, respectively. In the case of
      SRD edemas, the system correctly detected all the cases that were included in the
      designed dataset. CONCLUSIONS: The proposed methodology offered an accurate
      performance for the individual identification and characterization of the three
      different types of ME in OCT images. In fact, the method is capable to handle the
      ME analysis even in cases of significant severity with the simultaneous existence
      of the three ME types that appear merged inside the retinal layers.

PMID- 30119858
TI  - Lymphoma images analysis using morphological and non-morphological descriptors
      for classification.
AB  - Mantle cell lymphoma, follicular lymphoma and chronic lymphocytic leukemia are
      the principle subtypes of the non-Hodgkin lymphomas. The diversity of clinical
      presentations and the histopathological features have made diagnosis of such
      lymphomas a complex task for specialists. Computer aided diagnosis systems employ
      computational vision and image processing techniques, which contribute toward the
      detection, diagnosis and prognosis of digitised images of histological samples.
      Studies aimed at improving the understanding of morphological and non
      morphological features for classification of lymphoma remain a challenge in this
      area. This work presents a new approach for the classification of information
      extracted from morphological and non-morphological features of nuclei of lymphoma
      images. We extracted data of the RGB model of the image and employed contrast
      limited adaptive histogram equalisation and 2D order-statistics filter methods to
      enhance the contrast and remove noise. The regions of interest were identified by
      the global thresholding method. The flood-fill and watershed techniques were used
      to remove the small false positive regions. The area, extent, perimeter, convex
      area, solidity, eccentricity, equivalent diameter, minor axis and major axis
      measurements were computed for the regions detected in the nuclei. In the feature
      selection stage, we applied the ANOVA, Ansari-Bradley and Wilcoxon rank sum
      methods. Finally, we employed the polynomial, support vector machine, random
      forest and decision tree classifiers in order to evaluate the performance of the
      proposed approach. The non-morphological features achieved higher AUC and AC
      values for all cases: the obtained rates were between 95% and 100%. These results
      are relevant, especially when we consider the difficulties of clinical practice
      in distinguishing the studied groups. The proposed approach is useful as an
      automated protocol for the diagnosis of lymphoma histological tissue.

PMID- 30119859
TI  - New approaches to obtaining individual peak height velocity and age at peak
      height velocity from the SITAR model.
AB  - OBJECTIVE: We compared three methods for estimating the individual peak height
      velocity (PHV) and age at peak height velocity (APHV) from the SuperImposition by
      Translation and Rotation (SITAR) model. METHODS: We fitted the SITAR model using
      simulated data and heights of 12 girls from the Chard Growth Study and obtained
      individual PHVs and APHVs from three methods: the model method, the quadratic
      function method and the numerical method, which are available in our newly
      developed R package"iapvbs". The mean, interquartile range, range of biases in
      estimated APHV and PHV as well as the rates of warning and unreasonable cases,
      i.e. estimated APHVs being outside the range of age measurements, from the three
      methods were presented and compared. RESULTS: When the growth curves of all
      individuals were well fitted by the SITAR model, all three methods estimated
      individual APHVs with similarly small biases, with a few unreasonable cases
      (0.16%) observed when the model method was used while more computation time
      required for the numerical method. When the growth curves of some individuals
      were not very well fitted, the model method generated more unreasonable
      individual APHV (8.15%) and more bias in PHV and APHV, compared to those
      estimated by the numerical method and quadratic function method. In line with the
      observations from the simulated data, the real data analysis demonstrated that
      the numerical method generated more reliable PHV and APHV for individuals with
      growth curve not well fitted by the SITAR model. CONCLUSION: The performance of
      different methods estimating individual APHV depends largely on how well the
      growth curves are fitted by the SITAR model. The quadratic function method is
      more superior when growth curves of all individuals are well fitted by the SITAR
      model; otherwise, the numerical method should be adopted for getting most robust
      estimates of PHV and APHV. The model method generates unreasonable APHV
      estimates, particularly when the growth curves are not well fitted.

PMID- 30119861
TI  - The role of informatics in improving patient care.

PMID- 30119860
TI  - Fetal health status prediction based on maternal clinical history using machine
      learning techniques.
AB  - BACKGROUND AND OBJECTIVE: Congenital anomalies are seen at 1-3% of the
      population, probabilities of which are tried to be found out primarily through
      double, triple and quad tests during pregnancy. Also, ultrasonographical
      evaluations of fetuses enhance detecting and defining these abnormalities. About
      60-70% of the anomalies can be diagnosed via ultrasonography, while the remaining
      30-40% can be diagnosed after childbirth. Medical diagnosis and prediction is a
      topic that is closely related with e-Health and machine learning. e-Health
      applications are critically important especially for the patients unable to see a
      doctor or any health professional. Our objective is to help clinicians and
      families to better predict fetal congenital anomalies besides the traditional
      pregnancy tests using machine learning techniques and e-Health applications.
      METHODS: In this work, we developed a prediction system with assistive e-Health
      applications which both the pregnant women and practitioners can make use of. A
      performance comparison (considering Accuracy, F1-Score, AUC measures) was made
      between 9 binary classification models (Averaged Perceptron, Boosted Decision
      Tree, Bayes Point Machine, Decision Forest, Decision Jungle, Locally-Deep Support
      Vector Machine, Logistic Regression, Neural Network, Support Vector Machine)
      which were trained with the clinical dataset of 96 pregnant women and used to
      process data to predict fetal anomaly status based on the maternal and clinical
      data. The dataset was obtained through maternal questionnaire and detailed
      evaluations of 3 clinicians from RadyoEmar radiodiagnostics center in Istanbul,
      Turkey. Our e-Health applications are used to get pregnant women's health status
      and clinical history parameters as inputs, recommend them physical activities to
      perform during pregnancy, and inform the practitioners and finally the patients
      about possible risks of fetal anomalies as the output. RESULTS: In this paper,
      the highest accuracy of prediction was displayed as 89.5% during the development
      tests with Decision Forest model. In real life testing with 16 users, the
      performance was 87.5%. This estimate is sufficient to give an idea of fetal
      health before the patient visits the physician. CONCLUSIONS: The proposed work
      aims to provide assistive services to pregnant women and clinicians via an online
      system consisting of a mobile side for the patients, a web application side for
      their clinicians and a prediction system. In addition, we showed the impact of
      certain clinical data parameters of pregnant on the fetal health status,
      statistically correlated the parameters with the existence of fetal anomalies and
      showed guidelines for future researches.

PMID- 30119862
TI  - The Speech Efficiency Score (SES): A time-domain measure of speech fluency.
AB  - PURPOSE: This study is a preliminary attempt to evaluate a new speech fluency
      measure, the Speech Efficiency Score (SES), in comparison with subjective
      stuttering severity rating scales and stuttered syllable counts (%SS). METHODS:
      277 listeners (92 naive, 39 speech-language pathology (SLP) students, 124
      practicing SLPs, and 22 SLPs who specialize in stuttering) evaluated short
      recordings of speech on an 11-point scale. Recordings were obtained from 56
      adults, of whom 20 were people who stutter, 16 were people who stutter who were
      using fluency-shaping techniques, and 20 were speakers who do not stutter. In
      addition, %SS and the SES measure were obtained for each recording. RESULTS: The
      four listener groups rated stuttering severity similarly, with no statistically
      significant between-group differences. Listeners' responses on the stuttering
      severity rating scales and the SES yielded significant differences between all
      three speaker groups. The %SS measure yielded a significant difference only
      between the stuttering group and the other two groups but not between the fluency
      shaping and the control groups. A very strong positive correlation was found
      between the SES and the subjective stuttering-severity rating scales (r = 0.92).
      The correlation between %SS and the perceptual evaluation, as well as the
      correlation between %SS and the SES, were lower, though they still reached
      significance. CONCLUSIONS: Results suggest that speech efficiency scores, which
      are based on a time-domain analysis, closely match subjective stuttering severity
      ratings and could ultimately provide a more objective way to measure speech
      fluency.

PMID- 30119864
TI  - Psoas and neck abscess by Nocardia farcinica.

PMID- 30119865
TI  - Injection technique in neurotoxins and fillers: Planning and basic technique.
AB  - Cosmetic dermatologic surgery has evolved to be a minimally invasive field that
      addresses patient concerns with a multimodal approach while minimizing adverse
      events and downtime. Within the armamentarium of dermatologic surgery, injections
      of soft tissue augmentation materials and neuromodulators are key tools for
      recontouring the aging face. Treatment of the individual patient is preceded by a
      comprehensive consultation that elicits patient concerns and preferences. A
      treatment plan is collaboratively developed to correct relevant deficits and
      retreat as appropriate to maintain the correction. The goal of volumization with
      fillers is to recreate atrophic subcutis and dermis, thereby filling the deflated
      face and returning it to a more youthful contour. Neurotoxins can help minimize
      the emergence of static wrinkles and selectively recontour the face. Treatment
      techniques for both filler and neurotoxin injections are customized for
      particular patient needs and are based on the type of deficit and the anatomic
      location.

PMID- 30119863
TI  - Selective Mapping of Deep Brain Stimulation Lead Currents Using Acoustoelectric
      Imaging.
AB  - We describe a new application of acoustoelectric imaging for non-invasive mapping
      of the location, magnitude and polarity of current generated by a clinical deep
      brain stimulation (DBS) device. Ultrasound at 1MHz was focused near the DBS
      device as short current pulses were injected across different DBS leads. A
      recording electrode detected the high-frequency acoustoelectric interaction
      signal. Linear scans of the US beam produced time-varying images of the magnitude
      and polarity of the induced current, enabling precise localization of the DBS
      leads within 0.70mm, a detection threshold of 1.75mA at 1 MPa and a sensitivity
      of 0.52 +/- 0.07 MUV/(mA*MPa). Monopole and dipole configurations in saline were
      repeated through a human skullcap. Despite 13.8-dB ultrasound attenuation through
      bone, acoustoelectric imaging was still >10dB above background with a sensitivity
      of 0.56 +/- 0.10 MUV/(mA*MPa). This proof-of-concept study indicates that
      selective mapping of lead currents through a DBS device may be possible using non
      invasive acoustoelectric imaging.

PMID- 30119866
TI  - Injection technique in neurotoxins and fillers: Indications, products, and
      outcomes.
AB  - Injectable fillers and neuromodulators are used for a range of indications
      pertaining to the correction of facial aging and disfigurement. Fillers can
      correct soft tissue loss, depressed scars, and atrophy or asymmetry induced by
      systemic or local disease. Neuromodulators correct muscle-mediated skin creases,
      reshape the face, and address right-left functional asymmetry. Among the
      prepackaged injectable fillers approved by the US Food and Drug administration
      are hyaluronic acid derivatives, calcium hydroxylapatite, and poly-L-lactic acid;
      neuromodulators include three types of botulinum toxin type A and one type of
      type B. Adverse events associated with injections are typically mild, easily
      managed injection pain, followed by redness, swelling, and bruising. Asymmetry,
      nodules, ptosis, and intravascular occlusion are less common. Filler and toxin
      injections are part of a complete treatment plan. Reinjection is typically
      required to maintain the clinical effect, and combination treatment with laser
      and energy devices can enhance the aggregate effect.

PMID- 30119867
TI  - Primum non nocere: Anticholinergics and dementia.

PMID- 30119868
TI  - Association of atopic dermatitis with depression, anxiety, and suicidal ideation
      in children and adults: A systematic review and meta-analysis.
AB  - BACKGROUND: Atopic dermatitis (AD) has been associated with anxiety and
      depression, but the magnitude of the alleged association is unknown. OBJECTIVE:
      To perform a systematic review and meta-analysis of the association between AD in
      children and adults and, respectively, depression, anxiety, and suicidal
      behavior. METHODS: The medical databases PubMed, Embase, and PsychINFO were
      searched. RESULTS: There was a significant association between adult AD and,
      respectively, depression (pooled odds ratio [OR], 2.19; 95% confidence interval
      [CI], 1.87-2.57) and anxiety (pooled OR, 2.19; 95% CI, 1.75-2.73). AD was also
      associated with depression in children (pooled OR, 1.27; 95% CI, 1.12-1.45); few
      data were available for anxiety. A positive association was found between AD in
      adults and adolescents and suicidal ideation (pooled OR, 4.32; 95% CI, 1.93
      9.66). Only a few studies examined the risk of completed suicide, but the
      majority showed a positive association between completed suicide and AD.
      LIMITATIONS: Included studies used different definitions of depression and
      anxiety, and few studies examined the severity of AD. CONCLUSION: Depression,
      anxiety, and suicidal ideation should be considered by doctors when treating
      patients with AD. Because AD disease improvement appears to reduce these risks,
      this should be a priority.

PMID- 30119870
TI  - Dose escalation of doxepin for intractable pruritus.

PMID- 30119871
TI  - Response to "Vitamin D deficiency in patients with alopecia areata: A systematic
      review and meta-analysis" and an investigation of vitamin D in pediatric
      patients.

PMID- 30119869
TI  - Humanistic burden of chronic pruritus in patients with inflammatory dermatoses:
      Results of the European Academy of Dermatology and Venereology Network on
      Assessment of Severity and Burden of Pruritus (PruNet) cross-sectional trial.
AB  - BACKGROUND: Chronic pruritus is a multifactorial, challenging symptom of global
      relevance. OBJECTIVE: The European Academy of Dermatology and Venereology Network
      on Assessment of Severity and Burden of Pruritus (PruNet) investigation aimed to
      analyze the severity and humanistic burden of chronic pruritus in patients
      suffering from inflammatory dermatoses across Europe. METHODS: Prospectively
      collected routine data on 552 patients (with atopic dermatitis, contact
      dermatitis, prurigo nodularis, psoriasis vulgaris, lichen planus, or mycosis
      fungoides [pruritus numeric rating scale score >=3]) from 9 European centers (in
      Austria, France, Germany, Italy, Poland, Russia, Spain, Switzerland, and Turkey)
      were analyzed by univariate and multivariate variance analyses of various itch
      characteristics and quality of life (as measured by the Dermatology Life Quality
      Index and the ItchyQoL). RESULTS: Duration, frequency, and intensity of pruritus
      (according to a numeric rating scale and visual analog scale) and related
      impairment of quality of life differed between European centers and dermatologic
      diagnoses (P < .05). The country in which the center was located had a greater
      impact on how patients evaluated pruritus intensity and quality of life than
      diagnosis did (P < .001). LIMITATIONS: One center per country was included.
      CONCLUSION: The humanistic burden of chronic pruritus in patients with
      inflammatory dermatoses is high. European cross-cultural factors may have a
      stronger influence than a specific dermatologic diagnosis on how patients rate
      intensity of pruritus and quality of life.

PMID- 30119872
TI  - Operative time in esophagectomy: Does it affect outcomes?
AB  - BACKGROUND: The effect of operative duration on postoperative outcomes of
      esophagectomy is not well understood. The relationship between operative duration
      and postoperative complications was explored. METHODS: Esophagectomies with
      gastric reconstruction performed between 2010 and 2015 were queried from the
      National Surgical Quality Improvement Program. Linear and multivariate regression
      analyses were used to determine if operative duration correlated with outcomes
      independent of comorbidities. Subset analysis was performed by the type of
      esophagectomy. RESULTS: There were 5,098 patients with a median age and operative
      time of 64 years and 353 minutes, respectively. In the transhiatal group, longer
      operative times correlated with increased rates of pneumonia, prolonged
      intubation, unplanned reintubation, septic shock, unplanned reoperation, duration
      of stay, and mortality. For Ivor-Lewis esophagectomy, there were similar
      correlations with postoperative complications but not mortality. With the McKeown
      approach, there were no correlations between operative duration and postoperative
      outcomes. CONCLUSION: Prolonged operative time has an independent adverse impact
      on postoperative morbidity, which varies by surgical approach. We have identified
      unique cut points in the operative time for transhiatal (333 minutes) and Ivor
      Lewis esophagectomy (422 minutes), which can be used as a prognostic marker for
      postoperative outcomes as well as a quality metric in well-selected patients.

PMID- 30119873
TI  - Carbon monoxide intoxication: What we know.
AB  - Carbon monoxide (CO) is a toxic, color-, taste- and odorless gas with fatal
      consequences if undetected. Intoxication caused by CO is frequent possibly
      leading to a high morbidity and mortality. The disease involves multiple organ
      systems without a typical clinical presentation. The clinical picture is
      furthermore unrelated to levels of carboxyhemoglobin - the routine biomarker.
      Therefore the diagnosis and treatment can be very demanding. This article in
      detail reviews epidemiology, symptoms, diagnosis and the therapy of this
      multidisciplinary challenge.

PMID- 30119874
TI  - Structural Brain Connectivity in Childhood Disruptive Behavior Problems: A
      Multidimensional Approach.
AB  - BACKGROUND: Studies of white matter connectivity in children with disruptive
      behavior have yielded inconsistent results, possibly owing to the trait's
      heterogeneity, which comprises diverse symptoms like physical aggression,
      irritability, and delinquency. This study examined associations of global and
      specific white matter connectivity with childhood disruptive behavior problems,
      while accounting for their complex multidimensionality. METHODS: In a large cross
      sectional population-based study of 10-year-old preadolescents (n = 2567), we
      assessed four previously described empirically derived dimensions of disruptive
      behavior problems using the Child Behavior Checklist: physical aggression,
      irritability, disobedient behavior, and delinquent behavior. Global and specific
      white matter microstructure was assessed by diffusion tensor imaging. RESULTS:
      Global fractional anisotropy and mean diffusivity were not associated with broad
      measures of disruptive behavior, e.g., Child Behavior Checklist externalizing
      problems scale. Global fractional anisotropy was negatively associated with
      delinquent behavior (beta = -.123, pfalse discovery rate adjusted = .028) and
      global mean diffusivity was positively associated with delinquent behavior (beta
      = .205, pfalse discovery rate adjusted < 0.001), suggesting reduced white matter
      microstructure in preadolescents with higher levels of delinquent behavior. Lower
      white matter microstructure in the inferior longitudinal fasciculus, superior
      longitudinal fasciculus, cingulum, and uncinate underlie these associations.
      Global white matter microstructure was not associated with physical aggression,
      irritability, or disobedient behavior. CONCLUSIONS: Delinquent behavior, a severe
      manifestation of childhood disruptive behavior, was associated with lower white
      matter microstructure in tracts connecting frontal and temporal lobes. These
      brain regions are involved in decision making, reward processing, and emotion
      regulation. This study demonstrated that incorporating the multidimensional
      nature of childhood disruptive behavior traits shows promise in advancing the
      search for elucidating neurobiological correlates of disruptive behavior.

PMID- 30119875
TI  - Polygenic Risk and Neural Substrates of Attention-Deficit/Hyperactivity Disorder
      Symptoms in Youths With a History of Mild Traumatic Brain Injury.
AB  - BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a major sequela of
      traumatic brain injury (TBI) in youths. The objective of this study was to
      examine whether ADHD symptoms are differentially associated with genetic risk and
      brain structure in youths with and without a history of TBI. METHODS: Medical
      history, ADHD symptoms, genetic data, and neuroimaging data were obtained from a
      community sample of youths. ADHD symptom severity was compared between those with
      and without TBI (TBI n = 418, no TBI n = 3193). The relationship of TBI history,
      genetic vulnerability, brain structure, and ADHD symptoms was examined by
      assessing 1) ADHD polygenic score (discovery sample ADHD n = 19,099, control
      sample n = 34,194), 2) basal ganglia volumes, and 3) fractional anisotropy in the
      corpus callosum and corona radiata. RESULTS: Youths with TBI reported greater
      ADHD symptom severity compared with those without TBI. Polygenic score was
      positively associated with ADHD symptoms in youths without TBI but not in youths
      with TBI. The negative association between the caudate volume and ADHD symptoms
      was not moderated by a history of TBI. However, the relationship between ADHD
      symptoms and structure of the genu of the corpus callosum was negative in youths
      with TBI and positive in youths without TBI. CONCLUSIONS: The identification of
      distinct ADHD etiology in youths with TBI provides neurobiological insight into
      the clinical heterogeneity in the disorder. Results indicate that genetic
      predisposition to ADHD does not increase the risk for ADHD symptoms associated
      with TBI. ADHD symptoms associated with TBI may be a result of a mechanical
      insult rather than neurodevelopmental factors.

PMID- 30119876
TI  - Corrigendum to "Using critical flicker frequency in the evaluation of visual
      impairment in preeclamptic women" [Eur. J. Obstet. Gynecol. Reprod. Biol. 211
      (2017) 188-193].

PMID- 30119878
TI  - Artificial Intelligence as a Third Eye in Lesion Detection by Endoscopy.

PMID- 30119879
TI  - Reply.

PMID- 30119880
TI  - Correction.

PMID- 30119881
TI  - Increased sensitivity of Treg cells from patients with PBC to low dose IL-12
      drives their differentiation into IFN-gamma secreting cells.
AB  - IL-12 is a pro-inflammatory cytokine that induces the production of interferon
      gamma (IFNgamma) and favours the differentiation of T helper 1 (Th1) cells. In
      the presence of IL-12 human Treg cells acquire a Th1-like phenotype with reduced
      suppressive activity in vitro. Primary biliary cholangitis (PBC) is an autoimmune
      cholestatic liver disease characterised by high Th1 and Th17 infiltrating cells,
      reduced frequencies of Treg cells, and a genetic association with IL-12
      signalling. Herein, we sought to evaluate the IL-12 signalling pathway in PBC
      pathology, by studying human samples from patients with PBC, alongside those with
      primary Sjogren's syndrome (pSS)(autoimmune disease with IL-12 signalling gene
      association), primary sclerosing cholangitis (PSC) (cholestatic liver disease
      without IL-12 gene association) and healthy individuals. Our data revealed that
      TLR stimulation of PBC (n = 17) and pSS monocytes (n = 6) resulted in significant
      induction of IL12A mRNA (p < 0.05, p < 0.01, respectively) compared to PSC
      monocytes (n = 13) and at similar levels to HC monocytes (n = 8). PSC monocytes
      expressed significantly less IL-12p70 (108 pg/ml, mean) and IL-23 (358 pg/ml)
      compared to HC (458 pg/ml and 951 pg/ml, respectively) (p < 0.01, p < 0.05). Treg
      cells from patients with PBC (n = 16) and pSS (n = 3) but not PSC (n = 10) and HC
      (n = 8) responded to low dose (10 ng/ml) IL-12 stimulation by significant
      upregulation of IFNgamma (mean 277 and 254 pg/ml, respectively) compared to PSC
      and HC Treg cells (mean 22 and 77 pg/ml, respectively)(p < 0.05). This effect was
      mediated by the rapid and strong phosphorylation of STAT4 on Treg cells from
      patients with PBC and pSS (p < 0.05) but not PSC and HC. In the liver of patients
      with PBC (n = 7) a significantly higher proportion of IL-12Rbeta2+Tregs (16% on
      average) was detected (p < 0.05) compared to other liver disease controls (5%)(n
      = 18) which also showed ex vivo high IFNG and TBET expression. CONCLUSION: Our
      data show an increased sensitivity of PBC and pSS Treg cells to low dose IL-12
      stimulation, providing ongoing support for the importance of the IL12-IL-12Rbeta2
      STAT4 pathway on Treg cells in disease pathogenesis and potentially treatment.

PMID- 30119882
TI  - Avoidance sectors to reduce dosimetric impact of an irreproducible pannus on
      setup uncertainty in prostate SBRT VMAT: A case study.
AB  - This work investigates whether the use of an avoidance sector in a two-arc
      volumetric modulated arc therapy (VMAT) prostate stereotactic body radiotherapy
      (SBRT) plan reduces dosimetric variations due to an irreproducible pannus. A
      morbidly obese patient with favorable-risk prostate cancer elected treatment with
      SBRT. The patient was treated with the avoidance arcs across the pannus to
      eliminate reproducibility issues created by daily pannus variability in set up.
      For post-treatment assessment, the case was planned using Varian EclipseTM
      treatment planning system (TPS) with two VMAT arcs with and without 100 degrees 
      avoidance sectors across the pannus. The dose was re-calculated using the
      external body contour from four daily treatment cone-beam computer tomography
      scans, and on two virtual body contours created by expanding the pannus region of
      the external contour by 5 and 10 mm. Dose differences between planned and re
      calculated rectal wall mean dose and the V24Gy were numerically larger in the
      absence of the avoidance sector for all fractions and for both simulated pannus
      variations, with maximum changes of 2.6% and 1.3%. Maximum point dose variations
      in the PTV, CTV, rectum, bladder, and femoral heads were 105 cGy or less for all
      cases, with and without the avoidance sector. The use of an avoidance sector
      across this large, asymmetrical pannus did not inhibit achieving dose constraints
      and provided a reduction in dose variability which was nominal in this case for
      10 mm variations. Avoidance sectors can be safely implemented in cases with
      obvious reproducibility concerns in the setting of prostate VMAT SBRT.

PMID- 30119883
TI  - Characterization of a novel omega-transaminase from a Triassic salt mine
      metagenome.
AB  - Chiral amines are valuable building blocks for the pharmaceutical industry, and
      are increasingly synthesized by transaminase-mediated (TAm) synthesis. Currently
      available TAms, primarily isolated from the genomes of cultured mesophilic
      bacteria, often suffer from a number of drawbacks, including poor substrate range
      and an inability to tolerate the harsh conditions often demanded by industrial
      processes. These characteristics have, in part, driven the search for novel
      biocatalysts from both metagenomic sources and extreme environments. Herein, we
      report the isolation and characterization of an omega-TAm from a metagenome of a
      Triassic salt mine in Kilroot, N. Ireland, an extremely hypersaline environment
      formed circa 220-250 mya. The gene sequence was identified based on homology with
      existing bacterial TAms, synthesized within a pET28a(+) plasmid and expressed in
      E. coli BL21 DE3 cells. The resultant 49 kDa protein accepted (S)
      methylbenzylamine (MBA) as amino donor and had a specific activity of 0.54 U/mg
      using alpha-ketoglutarate (AlphaKG) as substrate. Molecular modeling and
      substrate docking indicated the presence of key residues, conserved in a number
      of other TAms. Despite the hypersaline environment from which it was isolated,
      the enzyme displayed low halotolerance, highlighting that not all biocatalysts
      will demonstrate the extreme characteristics associated with their source
      environment. This study does however reinforce the viability of mining
      metagenomic datasets as a means of discovering novel and functional biocatalysts,
      and adds to a currently scant list of such examples in the field of TAms.

PMID- 30119884
TI  - Adenovirus armed with VGLL4 selectively kills hepatocellular carcinoma with G2/M
      phase arrest and apoptosis promotion.
AB  - The Vestigial-Like Family Member 4 (VGLL4) functions as a native inhibitor of
      cell proliferation and tumor growth through multiple signaling pathways. We first
      discovered that VGLL4 causes G2/M phase arrest in hepatocellular carcinoma (HCC)
      cells. Then, we designed a novel survivin-regulated oncolytic adenovirus Ad-sp
      VGLL4 carrying the VGLL4 gene. Ad-sp-VGLL4 exerted high HCC-targeting-selectivity
      but is less harmful to normal cells. This adenovirus construction enhanced
      antitumor activity due to G2/M phase arrest and enhanced apoptosis. It's also
      indicated that Ad-sp-VGLL4 could suppress the growth of transplanted tumor of HCC
      in vivo experiment. Taken together, our results suggest that Ad-sp-VGLL4
      possesses strong antitumor capacity and has great potential use for HCC therapy.

PMID- 30119885
TI  - Effects of amino acid substitutions on the biological activity of anti-CD20
      monoclonal antibody produced by transgenic silkworms (Bombyx mori).
AB  - Recombinant monoclonal antibodies (mAbs) have been used in various therapeutic
      applications including cancer therapy. Fc-mediated effector functions play a
      pivotal role in the tumor-killing activities of some tumor-targeting mAbs, and Fc
      engineering technologies with glyco-engineering or amino acid substitutions at
      the antibody Fc region have been used to enhance cytotoxic activities including
      antibody-dependent cellular cytotoxicity (ADCC). We previously reported that the
      mAbs produced using transgenic silkworms showed stronger ADCC activity and lower
      complement-dependent cytotoxicity (CDC) activity than mAbs derived from Chinese
      hamster ovary (CHO) cells due to their unique N-glycan structure (lack of core
      fucose and non-reducing terminal galactose). In this study, we generated anti
      CD20 mAbs with amino acid substitutions using transgenic silkworms and analyzed
      their biological activities to assess the effect of the combination of glyco
      engineering and amino acid substitutions on the Fc-mediated function of mAbs.
      Three types of amino acid substitutions at the Fc region (G236A/S239D/I332E,
      L234A/L235A, and K326W/E333S) modified the Fc-mediated biological activities of
      silkworm-derived mAbs as in the case of CHO-derived mAbs, resulting in the
      generation of Fc-engineered mAbs with characteristic Fc-mediated functions. The
      combination of amino acid substitutions at the Fc region and glyco-engineering
      using transgenic silkworm made it possible to generate Fc-engineered mAbs with
      suitable Fc-mediated biological functions depending on the pharmacological
      mechanism of their actions. Transgenic silkworms were shown to be a promising
      system for the production of Fc-engineered mAbs.

PMID- 30119886
TI  - Valproic acid promotes the neuronal differentiation of spiral ganglion neural
      stem cells with robust axonal growth.
AB  - Hearing loss occurs with the loss of hair cells of the cochlea and subsequent
      degeneration of spiral ganglion neurons (SGNs). Regeneration of SGNs is a
      potentially promising therapeutic approach to hearing loss in addition to the use
      of a cochlear implant (CI), because this device stimulates SGNs directly to
      restore hearing bypassing the missing hair cells. The presence of SGN-neural stem
      cells (NSCs) has been reported in adult human and mice. These cells have the
      potential to become SGNs and thus represent a cellular foundation for
      regeneration therapies for hearing loss. Valproic acid (VPA) has been shown to
      influence the neural differentiation of NSCs through multiple signaling pathways
      involving glycogen synthase kinase3beta (GSK3beta). Our present study therefore
      aimed to modulate the neural differentiation potential of SGN-NSCs by treatment
      with VPA. We here report that a clinically relevant concentration of 1 mM VPA
      induced the differentiation of basic fibroblast growth factor (bFGF)-treated P1-
      and P14-SGN-NSCs into neuronal and glial cells, confirmed by neuronal marker
      (Tuj1 and MAP2) and glial cell marker (GFAP and S100beta) detection. VPA-treated
      cells also promoted much longer neurite outgrowth compared to differentiated
      cells cultured without bFGF. The effects of VPA on the regulation of
      differentiation may be related to the activation of the Wnt/beta-catenin
      signaling pathway, but not the inhibition of histone deacetylases (HDACs). We
      propose that VPA has the potential to convert SGN-NSCs into SGNs and thereby
      restore hearing when combined with a CI.

PMID- 30119887
TI  - Insulin-like growth factor I receptor regulates the radiation-induced G2/M
      checkpoint in HeLa cells.
AB  - Insulin-like growth factor I receptor (IGF-IR) plays pivotal roles in various
      biological events, including cell growth, transformation, survival, and DNA
      repair. In this study, we explored its possible involvement in cell cycle
      checkpoints, using HeLa cells expressing the fluorescent ubiquitination-based
      cell cycle indicator (Fucci). We found that IGF-IR inhibitor delayed release from
      radiation-induced G2 arrest, as demonstrated by FACS and pedigree analysis of
      Fucci fluorescence. Elongated G2 arrest was also induced by inhibitors of
      phosphatidylinositol-3 kinase (PI3K) and AKT, but not by inhibitor of MEK, which
      are two major IGF-IR downstream signaling pathways. Double-strand break (DSB)
      repair kinetics were not affected by IGF-IR inhibitor. CHK1 inhibitor abrogated
      radiation-induced G2 arrest, whereas radiation-induced phosphorylation of CHK1 at
      Ser 345 or Ser 296 was decreased by the IGF-IR inhibitor. However, radiation
      induced nuclear localization of CHK1 was prolonged in IGF-IR inhibitor-treated
      cells in comparison with cells that received radiation alone; in the latter, CHK1
      returned to the original diffuse distribution in conjunction with release from G2
      arrest. We conclude that IGF-IR directly regulates the G2/M checkpoint via the
      PI3K/AKT pathway without influencing DSB repair, in part by controlling CHK1
      localization between the nucleus and cytoplasm.

PMID- 30119888
TI  - Role of PKB/SGK-dependent phosphorylation of GSK-3alpha/beta in vascular
      calcification during cholecalciferol overload in mice.
AB  - Medial vascular calcification is a highly regulated process involving osteo
      /chondrogenic transdifferentiation of vascular smooth muscle cells. Both, protein
      kinase B (PKB) and serum- and glucocorticoid-inducible kinase 1 (SGK1) are
      involved in the intracellular signaling of vascular calcification and both
      phosphorylate and inactivate glycogen synthase kinase 3 (GSK-3). The present
      study explored whether PKB/SGK-dependent phosphorylation of GSK-3alpha/beta is
      involved in vascular calcification. Experiments were performed in Gsk-3alpha/beta
      double knockin mice lacking functional PKB/SGK phosphorylation sites (gsk-3KI)
      and corresponding wild-type mice (gsk-3WT) following high-dosed cholecalciferol
      treatment as well as ex vivo in aortic ring explants from gsk-3KI and gsk-3WT
      mice treated without and with phosphate. In gsk-3WT mice, high-dosed
      cholecalciferol induced vascular calcification and aortic osteo-/chondrogenic
      signaling, shown by increased expression of osteogenic markers Msx2, Cbfa1 and
      tissue-nonspecific alkaline phosphatase (Alpl). All these effects were suppressed
      in aortic tissue from gsk-3KI mice. Cholecalciferol decreased aortic Gsk
      3alpha/beta phosphorylation (Ser21/9) in gsk-3WT mice, while no phosphorylation
      was observed in gsk-3KI mice. Moreover, the mRNA expression of type III sodium
      dependent phosphate transporter (Pit1) and plasminogen activator inhibitor 1
      (Pai1) was increased following cholecalciferol treatment in aortic tissue of gsk
      3WT mice, effects again blunted in gsk-3KI mice. In addition, phosphate treatment
      induced mineral deposition and osteogenic markers expression in aortic ring
      explants from gsk-3WT mice, effects reduced in aortic ring explants from gsk-3KI
      mice. In conclusion, vascular PKB/SGK-dependent phosphorylation of GSK
      3alpha/beta contributes to the osteoinductive signaling leading to vascular
      calcification.

PMID- 30119890
TI  - Effects of saponins of patrinia villosa against invasion and metastasis in
      colorectal cancer cell through NF-kappaB signaling pathway and EMT.
AB  - BACKGROUND: Research has indicated that Herba Patriniae can suppress the growth
      of Several kinds of tumor cells in vitro and in vivo, thus displaying favorable
      antitumor activity. However, research regarding the effect of saponins of
      Patrinia villosa against CRC cell has not been reported. In the current study, We
      have revealed that the effects of saponins of patrinia villosa on colorectal
      cancer (CRC) cell invasion and epithelial-mesenchymal transition (EMT) as well as
      its underlying mechanism. METHODS: The CRC EMT model was induced through repeated
      TGF-beta1 stimulations on human CRC cell line SW480. Effects of saponins of
      patrinia villosa at various concentrations on CRC SW480 cell and EMT model cell
      proliferation were detected using MTT method, so as to select the optimal action
      concentration. Meanwhile, effects on SW480 cell and EMT model cell invasion were
      determined through Scratch assay and Transwell assay. Moreover, changes in
      expression of EMT-related proteins E-cadherin, N-cadherin and NF-KappaBp65 in
      each group were detected through Western blotting. RESULTS: Saponins of patrinia
      villosa at various concentrations could markedly inhibit the proliferation rate
      of CRC cell in an obvious concentration-dependent manner. Meanwhile, saponins of
      patrinia villosa at various concentrations could also remarkably suppress
      migration of cell developing EMT. In addition, the protein expression of E
      cadherin and N-cadherin was down-regulated with the increase in saponins of
      patrinia villosa concentration, while that of NF-KBp65 was notably down
      regulated. CONCLUSION: Saponins of patrinia villosa can act against tumor
      invasion and metastasis through inhibiting EMT in human CRC cell line, which may
      be achieved through down-regulating the NF-kappaB signaling pathway.

PMID- 30119889
TI  - DDX5 promotes hepatocellular carcinoma tumorigenesis via Akt signaling pathway.
AB  - The DEAD-box-protein DDX5 is an ATP-dependent RNA helicase and also acts as co
      activator that contributes to progression and metastasis of various tumours.
      However, its expression as well as prognostic roles of DDX5 in hepatocellular
      carcinoma (HCC) remain elusive. In this study, we investigated clinical
      significance and biological functions of DDX5 in HCC. Our results suggested that
      DDX5 showed overexpression at both transcriptional and translational levels in
      HCC tissues compared with adjacent normal tissues. Moreover, DDX5 expression was
      demonstrated to be correlated with tumor size (p < 0.001), N stage (p = 0.013), M
      stage (p = 0.006), tumor differentiation (p < 0.001) and American Joint Committee
      on Cancer (AJCC) stage (p = 0.001). Simultaneously, high DDX5 expression was
      found to be significantly correlated to worse outcome including Disease free
      survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.032) according to
      Kaplan-Meier survival analysis. In vitro studies, it suggested that knockdown of
      DDX5 suppressed HCC cells migration, invasion and epithelial -to- mesenchymal
      transition (EMT) process. Depletion of DDX5 could promote HCC cells growth. Kyoto
      Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that
      PI3K/Akt signaling pathway obtained the highest enrichment. Furthermore, we found
      that knockdown of DDX5 decreased Akt as well as p-Akt (S473) expressions.
      Collectively, these findings suggested that DDX5 facilitated HCC cells growth via
      Akt signaling pathway. DDX5 played a crucial role in HCC proliferation and
      tumorigenesis and may be a novel prognostic marker and potential therapeutic
      target for HCC.

PMID- 30119891
TI  - MicroRNA-30c-5p inhibits NLRP3 inflammasome-mediated endothelial cell pyroptosis
      through FOXO3 down-regulation in atherosclerosis.
AB  - Atherosclerosis is a chronic inflammatory disease involved in endothelial
      dysfunction. Pyroptosis is a pro-inflammatory form of cell death and plays
      pivotal roles in atherosclerosis. MicroRNAs (miRNAs) are implicated in
      atherosclerosis, however the mechanisms that underlie miR-30c-5p is required for
      endothelial cell pyroptosis remain elusive. In the present study, we probed the
      interaction of miR-30c-5p with forkhead box O3 (FOXO3) and investigated the
      effect of miR-30c-5p and FOXO3 on NLRP3 inflammasome and endothelial cell
      pyroptosis. Introduction of oxidized low density lipoprotein (ox-LDL) dose
      dependently increased lactate dehydrogenase (LDH) release as well as pyroptosis
      in human aortic endothelial cells (HAECs). On the basis of ox-LDL treatment, we
      found the expression of miR-30c-5p was impaired and enrichment of miR-30c-5p
      protected HAECs from ox-LDL-induced pyroptosis. Moreover, addition of miR-30c-5p
      inhibited ox-LDL-activated NOD-like receptor family pyrin domain-containing 3
      (NLRP3) inflammasome, which was associated with HEACs pyroptosis. Nevertheless,
      miR-30c-5p failed to show efficacy of Toll-like receptor (TLR) signaling of NLRP3
      inflammasome activation. Intriguingly, FOXO3 was suggested to be targeted by miR
      30c-5p and addition of miR-30c-5p blocked FOXO3 expression, whereas miR-30c-5p
      depletion showed opposite effects. Furthermore, silencing of FOXO3 inhibited
      NLRP3-mediated pyroptosis and reversed anti-miR-30c-5p-induced activation of
      NLRP3 inflammasome and pyroptosis in HEACs with ox-LDL treatment. Our finding
      suggested that miR-30c-5p might play essential role in NLRP3 inflammasome
      modulated cell pyroptosis by targeting FOXO3 in HAECs, providing a novel
      therapeutic avenue for atherosclerosis treatment.

PMID- 30119892
TI  - A revisit of the conformational dynamics of SNARE protein rYkt6.
AB  - N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins
      are involved in the fusion of vesicles with their target membranes. R-SNARE
      protein Ykt6 is one of the most conserved SNARE in eukaryotes. The conformational
      state of Ykt6 is regulated by the lipidations at its C-terminal motif. Previous
      studies show that the binding of dodecylphosphocholine (DPC) can stabilize a
      closed conformation of rat Ykt6 (rYkt6) and mimic the farnesylated rYkt6. Despite
      this model, the detailed conformational dynamics of Ykt6 is still unclear. Here,
      we combined smFRET and MD simulation to demonstrate that the un-lipidated rYkt6
      adopts five major conformational states. DPC binding shifts the conformational
      distribution toward the more closed states. At the same time, there remain
      considerable fractions of open and semi-open conformations in the presence of
      DPC. These newly revealed dynamic features of rYkt6 are consistent with its
      unique functional diversity in neuronal cells.

PMID- 30119894
TI  - Probing the light scattering properties of insulin secretory granules in single
      live cells.
AB  - Light scattering was recently demonstrated to serve as an intrinsic indicator for
      pancreatic islet cell mass and secretion. The insulin secretory granule (ISG), in
      particular, was proposed to be a reasonable candidate as the main intracellular
      source of scattered light due to the densely-packed insulin semi-crystal in the
      granule lumen. This scenario, if confirmed, would in principle open new
      perspectives for label-free single-granule imaging, tracking, and analysis.
      Contrary to such expectations, here we demonstrate that ISGs are not a primary
      source of scattering in primary human beta-cells, as well as in immortalized beta
      like cells, quantitatively not superior to other intracellular
      organelles/structures, such as lysosomes and internal membranes. This result is
      achieved through multi-channel imaging of scattered light along with fluorescence
      arising from selectively-labelled ISGs. Co-localization and spatiotemporal cross
      correlation analysis is performed on these signals, and compared among different
      cell lines. Obtained results suggest a careful re-thinking of the possibility to
      exploit intrinsic optical properties originating from ISGs for single-granule
      imaging purposes.

PMID- 30119895
TI  - Tribute to Glyn W. Humphreys, 1954-2016.

PMID- 30119893
TI  - Anti-survivin single-domain antibodies derived from an artificial library
      including three synthetic random regions by in vitro selection using cDNA
      display.
AB  - Single-domain antibodies (variable domain of the heavy chain of a heavy chain
      antibody; VHH) are promising reagents for therapeutics and diagnostics because of
      their stability, cost-effective production and material workability as a small
      antibody. Currently, general acquisition of a VHH using immunization of camelids
      is inconvenient from the standpoint of animal protection, cost and the process is
      time-consuming. Thus, a straightforward and efficient method for screening VHHs
      against a target molecule is required. In this study, we examined whether in
      vitro selection of a VHH against a target protein could be performed by a cDNA
      display method with an artificial VHH library that had the three complementarity
      determining regions (CDRs) randomized by chemical synthesis. The results revealed
      that a particular VHH against survivin, which is a member of the inhibitor of
      apoptosis family, was selected with affinity in the range of 10-7 to 10-8 M. The
      in vitro selection of a VHH using cDNA display with an artificial synthesized
      library without animal immunization was shown to be effective for rapid and
      inexpensive screening of VHHs against a target protein.

PMID- 30119896
TI  - Sexual dimorphism of body size in an African fossil ape, Nacholapithecus kerioi.
AB  - Sexual size dimorphism in the African fossil ape Proconsul nyanzae (18 million
      years ago, 18 Ma) has been previously documented. However, additional evidence
      for sexual dimorphism in Miocene hominoids can provide great insight into the
      history of extant hominoid mating systems. The present study focused on body mass
      (BM) sexual dimorphism in Nacholapithecus kerioi from the Middle Miocene (16-15
      Ma) in Africa. Bootstrap analysis revealed that P. nyanzae BM sexual dimorphism
      was lower than that in Pan troglodytes, which exhibits moderate sexual
      dimorphism, as reported previously. The same simulation revealed that BM sexual
      dimorphism of N. kerioi was comparable with that in Gorilla spp.; i.e., the males
      were approximately twice as large as the females. High sexual dimorphism in
      extant apes is usually indicative of a polygynous social structure (gorilla) or
      solitary/fission-fusion social system (orangutan). However, because of the high
      proportion of adult males in this fossil assemblage, the magnitude of dimorphism
      inferred here cannot be associated with a gorilla-like polygynous or oranguran
      like solitary/fission-fusion social structure, and may reflect either taphonomic
      bias, or some other social structure. Extant hominoids have a long evolutionary
      history owing to their deep branching, comprising only a few existing members of
      the original highly successful group. Therefore, it is not surprising that the
      mating systems of extant hominoids fail to provide fossil apes with a perfect
      "model". The mating systems of extinct hominoids may have been more diverse than
      those of extant apes.

PMID- 30119897
TI  - Adaptive control for spacecraft rendezvous subject to actuator faults and
      saturations.
AB  - An adaptive saturated fault-tolerant controller is proposed for a spacecraft
      rendezvous maneuver with a cooperative target spacecraft. The six-degree-of
      freedom (6-DOF) relative dynamics subject to unknown inertial parameters,
      external disturbances, actuator faults and saturations are formulated in the
      pursuer's body-fixed frame. To design controller satisfying asymmetric magnitude
      constraints, a modified smooth hyperbolic tangent function is applied to
      approximate the non-differentiable saturation function. Based on the augmented
      system technique, an adaptive fault-tolerant saturated controller is designed for
      the pursuer by using a Nussbaum function matrix compensating for the nonlinear
      term arising from the input saturations. In addition, a Levant differentiator is
      introduced to obtain the derivative of the virtual control in finite time that
      avoids the complicated calculation. It is proved via Lyapunov stability theory
      that all the signals in the closed-loop augmented system are bounded and the
      relative errors asymptotically converge to zero. Numerical simulations are
      performed to illustrate effectiveness of the proposed controller.

PMID- 30119899
TI  - Short- and intermediate-term outcomes of hybrid coronary revascularization for
      double-vessel disease.
AB  - OBJECTIVE: We sought to evaluate midterm survival data and resource use for
      patients who received hybrid coronary revascularization for 2-vessel coronary
      disease (robotic-assisted left internal thoracic artery graft to left anterior
      descending coronary artery (minimally invasive direct coronary artery bypass),
      coupled with a stent to the circumflex or right coronary artery), compared with a
      concurrent cohort who had traditional coronary artery bypass grafting. METHODS: A
      comprehensive retrospective review was undertaken of our prospectively collected
      database from January 2009 to December 2016. We propensity matched 207 patients
      who underwent hybrid coronary revascularization for double-vessel disease with
      patients who underwent coronary artery bypass grafting. Eight-year survival data
      were obtained from the National Death Index. RESULTS: Thirty-day mortality was 1
      patient (0.5%) in each of the hybrid coronary revascularization and coronary
      artery bypass grafting groups. Eight-year survival for the hybrid coronary
      revascularization group was 187 of 207 patients (90.3%) compared with 182 of 207
      patients (87.9%) for the coronary artery bypass grafting cohort. End-stage renal
      disease independently predicted late mortality in all patients (overall hazard
      ratio, 5.60, P < .001; hybrid coronary revascularization hazard ratio, 5.58, P =
      .002; coronary artery bypass grafting hazard ratio, 4.59, P = .006). Female
      patients who underwent hybrid coronary revascularization had a higher incidence
      of late death (hazard ratio, 2.47, P = .05). Length of stay and perioperative
      transfusion requirements were lower in the hybrid coronary revascularization
      group (P < .0001). CONCLUSIONS: Hybrid coronary revascularization for double
      vessel coronary disease is associated with similar short-term outcomes and
      intermediate-term survival as traditional coronary artery bypass grafting. Hybrid
      coronary revascularization is associated with lower transfusion requirements and
      a shorter length of stay than coronary artery bypass grafting.

PMID- 30119900
TI  - A comparison of efficacy and safety of preoperative versus intraoperative
      computed tomography-guided thoracoscopic lung resection.
AB  - BACKGROUND: The efficacy and safety of intraoperative computed tomography (IOCT)
      guided lung tumor localization and resection performed in a hybrid operating room
      (OR) compared with the conventional 2-stage preoperative CT (POCT)-guided
      approach for the treatment of small and deep solitary pulmonary nodules (SPNs)
      remains unknown. METHODS: We compared IOCT-guided (IOCT group) and POCT-guided
      (POCT group) thoracoscopic resections in 64 consecutive patients with SPNs. The
      main outcome measures included efficacy, safety, and radiation exposure. RESULTS:
      The IOCT (n = 34) and POCT (n = 30) groups had a similar SPN depth-to-size ratio.
      All SPNs were successfully localized and removed using a minimally invasive
      approach. There were no significant intergroup differences in localization
      procedural time (mean, 17.68 [IOCT] vs 19.63 minutes [POCT]; P = .257) and
      radiation exposure (median, 3.65 [IOCT] vs 6.88 mSv [POCT]; P = .506). The use of
      a hybrid operating room (OR) for tumor localization significantly reduced the
      patient time at risk (ie, the interval from completion of localization to skin
      incision; mean, 215.83 [POCT] vs 13.06 minutes [IOCT]; P < .001). However, the
      IOCT-guided approach significantly increased the time under general anesthesia
      (mean, 120.61 [POCT] vs 163.1 minutes [IOCT]; P < .001) and the total OR
      utilization time (mean, 168.68 [POCT] vs 227.41 minutes [IOCT]; P < .001).
      CONCLUSIONS: Compared with the POCT-guided approach, the IOCT-guided approach
      decreased the time at risk, despite a significant increase in the global OR
      utilization time. Because no significant outcome differences were evident, the
      choice between the 2 approaches should be based on the most readily available
      approach at a surgeon's specific facility.

PMID- 30119902
TI  - Systemic atrioventricular valve replacement with a Melody valve in an infant with
      a single-ventricle physiology.

PMID- 30119901
TI  - Transcatheter aortic valve replacement: Can we get through the turbulence?

PMID- 30119903
TI  - Pharmacotherapy for closure of large patent ductus arteriosus in preterm
      neonates: Fail once, not twice.

PMID- 30119904
TI  - Appraisal of mentorship in cardiothoracic surgery training.
AB  - OBJECTIVES: Although the importance of mentorship in training the next generation
      of cardiothoracic surgeons is widely recognized, the current state of mentorship
      remains undefined. METHODS: Trainee responses to questions in the 2017 In
      Training Examination regarding aspects of mentorship were analyzed. Response rate
      was 78% (288/370). Mentor-related and trainee-related characteristics were
      assessed. RESULTS: The majority (84%) of residents had mentors, with a high
      impact on specialty choice (80%), and 91% of respondents viewed mentorship as
      critical to success. Nearly half (42%) had program-assigned mentors; 53% found
      them as productive, and 13% reported more consistent/frequent meetings than
      personally selected mentors, with 22% reporting less ideal personality match
      compared with personally selected mentors. Among residents with mentors, 36%
      lacked mentorship in work-life balance, 23% lacked mentorship in job assistance,
      and 22% lacked mentorship in career advice. Junior residents more often valued
      mentors as role models, whereas mentors chosen by senior residents were more
      impactful in technical training, job counseling, and societal involvement.
      Compared with men, women more often valued mentors as role models and assisting
      in networking. Men reported their mentors were more impactful in teaching
      technical skills and clinical ability than women. CONCLUSIONS: The majority of
      current cardiothoracic surgery trainees had mentorship; however, gaps remain:
      Many residents lacked career path guidance, assistance obtaining a job, and
      advice regarding life-work balance. The role of mentorship varied with program
      type, seniority, and gender, emphasizing the need to tailor mentorship to the
      individual and changing needs of the resident.

PMID- 30119906
TI  - Enhanced exosomes and spinal cord ischemia: Excitement and a Nobel Prize but more
      to come.

PMID- 30119905
TI  - Observed to expected mortality ratio as the new gold standard: All that glitters
      is not gold.

PMID- 30119907
TI  - Which came first, the risk of migraine or the risk of asthma? A systematic
      review.
AB  - OBJECTIVES: We conducted this review to systematically assess the association and
      risk of the migraine in the patient with asthma and vice versa. METHODS: We
      systematically searched publishes articles indexed in PubMed, Scopus, Cochrane
      library, PsycINFO, CINAHL, ISI Web of Science, Science Direct from inception, and
      Embase databases until June 2017. The quality assessment of the involved studies
      was done using the Newcastle-Ottawa Scale (NOS). RESULTS: Eight studies with
      389,573 participants were reviewed and selected for data extraction. Among the
      selected studies, 5 were reported the association between migraine with asthma
      risk, and the rest three studies reported the risk of asthma in patient with
      migraine compared to non-moraine individuals. Odds ratio (OR) of migraine for
      patient with asthma as compared with non-asthmatic individuals was 1.62 (95% CI
      1.43-1.82). Data pooling using a random-effect model showed that migraine was
      associated with a significant increased risk of asthma (relative risk (RR): 1.56;
      95% CI: 1.51-1.60; p < .00001). Besides, sub-group and sensitivity analyses
      supported the positive association between asthma and migraine, and risk of
      asthma in migraine patients. CONCLUSION: Now it is unknown if control of the
      asthma will impact the severity of migraines or vice versa, but it is necessary
      to perform more research to further explain the mechanisms through which asthma
      increases the frequency of migraine or vice versa. If two conditions linked, once
      an individual undergo better control of asthma symptoms, might the excruciating
      migraine ease, too.

PMID- 30119908
TI  - CPX-351 exhibits hENT-independent uptake and can be potentiated by fludarabine in
      leukaemic cells lines and primary refractory AML.
AB  - CPX-351, a liposomal formulation co-encapsulating cytarabine and daunorubicin
      (DNR) in a synergistic 5:1 M ratio, has shown favourable response in newly
      diagnosed elderly high-risk AML. This study assessed intracellular ara-CTP levels
      following in vitro exposure of human immortalised leukaemic cell lines and
      primary AML blasts to CPX-351, and investigated fludarabine potentiation of
      intracellular ara-CTP formation from CPX-351. Comparison of intracellular
      handling of CPX-351 to cytarabine in HL-60 cells indicated slower conversion to
      ara-CTP for CPX-351, but equivalent cytotoxicity to cytarabine and combined
      DNR/cytarabine (DA) at 48 h, mostly likely reflecting the need for intracellular
      liposome processing to release encapsulated drugs. Further assessment
      demonstrated cytotoxicity of CPX-351 to be superior to DA at 48 and 72 h in
      cytarabine-resistant THP-1 cells (p < 0.001), and this effect could not be
      inhibited upon blockade of human equilibrative nucleoside transporter (hENT)
      function with dipyridamole. Assessment of Flu-CPX in primary blasts from
      presentation AML patients (n = 5) demonstrated a more rapid and pronounced
      potentiation of ara-CTP from CPX-351 than in immortalised cell lines, with 4/5
      patients showing significant increases in ara-CTP, notably for those that went on
      to fail induction and relapse treatment in vivo (n = 3). This suggests a
      favourable impact on patient outcome from Flu-CPX.

PMID- 30119909
TI  - Outcome comparisons of high-grade glioma resection with or without fluorescein
      sodium-guidance.
AB  - PURPOSE: To compare surgical outcomes and adverse events between patients
      received microsurgical resection of high-grade gliomas with or without
      fluorescein sodium-guidance. PATIENTS: A retrospective study was conducted in our
      hospital between June 2016 and January 2017. Patients were divided into 2 groups:
      Fluorescein Group (42 patients) and Nonfluorescein Group (40 patients).
      MEASUREMENTS: Intraoperative (hemorrhage value and operation time) and
      postoperative (consistency between fluorescence-stained tissue and
      histopathological results, rate of resection) measurements were documented.
      Postoperative adverse events were recorded. Patients were followed up for 6
      months to evaluate postsurgery glioma recurrence. MAIN RESULTS: Intraoperatively,
      hemorrhage value, and operation time were significantly less in Fluorescencein
      than in Nonfluorescencein group. The rate of glioma complete resection was
      significantly higher in Fluorescencein than in Nonfluorescencein group (85.7%vs
      62.5%, P = 0.02). The rate of glioma recurrence was significantly lower in
      Fluorescencein than in Nonfluorescencein group (11.9%vs 25.0%, P = 0.01), and no
      significant differences on adverse events were observed. CONCLUSIONS:
      Intraoperative fluorescein sodium-guidance could facilitate the complete
      resection and significantly decrease the postoperative recurrence in patients
      with high-grade gliomas.

PMID- 30119910
TI  - Laryngeal metastases from breast cancer: A rare clinical entity.
AB  - Breast cancer is the most common malignancy in females. The common site for
      metastases is bone, lungs, liver, and regional lymph nodes. Larynx as a
      metastatic site from breast cancer is extremely rare. The authors report a 63
      year-old female treated for carcinoma of right breast 5 years back who presented
      with hoarseness of voice. Clinicoradiological examination revealed a soft tissue
      lesion in larynx. Pathological evaluation of the laryngeal lesion revealed
      metastases secondary to breast cancer. The patient received systemic chemotherapy
      and local radiotherapy. Patients with a history of breast cancer presenting with
      hoarseness and shortness of breath should not only be evaluated for laryngeal
      primary but also for metastases. This case is reported in view of rarity of the
      case with laryngeal metastases from breast cancer masquerading as primary
      laryngeal disease. To the best of our knowledge, less than 20 cases of laryngeal
      metastases from breast cancer had been reported in literature till date. Patients
      with a history of breast cancer presenting with hoarseness and shortness of
      breath should not only be evaluated for laryngeal primary but also for
      metastases. Once the diagnosis is confirmed, the treatment of laryngeal
      metastases is multidisciplinary. Recognizing metastatic disease and prompt early
      treatment are very important to improve the quality of life.

PMID- 30119911
TI  - The impact of microsatellite stability status in colorectal cancer.
AB  - Several forms of genomic instability are known to drive the development of
      colorectal cancer (CRC). Chromosomal instability is the most common type found in
      85% of the CRC, while 15% patients have microsatellite instability (MSI). MSI
      tumors are the subset of CRC that are characterized by dysfunction of mismatch
      repair genes (MMR) causing failure to repair errors in repetitive DNA sequences
      called microsatellites. Twelve percent of MSI tumors are acquired, caused by
      methylation-associated silencing of a gene that encodes a DNA MMR protein, while
      the remaining 3% have germline mutations in one of the MMR genes (Lynch
      syndrome). The identification of microsatellite stability status is clinically
      important as studies have revealed that MSI tumors have a better stage-adjusted
      survival compared with microsatellite stable tumors, and they respond differently
      to 5FU-based adjuvant chemotherapy depending on this status. There is recent
      success of immunotherapy (mainly anti-PD1 drugs) in metastatic CRC with MMR
      dysfunction that has led to the initiation of multiple trials based on immune
      checkpoint inhibitors. Additionally, it is important to identify patients with
      Lynch syndrome so that it can guide the frequency of surveillance of CRCs and
      recommendations of prophylactic surgery. Even though TNM staging remains a key
      determinant of patient prognosis and guides management in patients with CRC,
      molecular tumor heterogeneity contributes to significant variability in clinical
      outcomes despite the same disease stage; therefore, it is vital to know the type
      of genomic instability pathway that the tumor harbors. In this article, we
      discuss the unique genetic, pathologic, and clinical characteristics of
      microsatellite unstable (MSI) and stable CRC (MSS), their predictive value in
      directing the management with conventional chemotherapy or novel-targeted agents,
      and their prognostic significance in patient outcomes.

PMID- 30119912
TI  - Should adjuvant chemotherapy be recommended to a 75-year-old woman with deficient
      mismatch repair (dMMR) gene product expression seen in a stage II colon
      adenocarcinoma with lymphovascular invasion?
AB  - The risk of recurrence from stage II colon cancer and benefit from adjuvant
      chemotherapy is influenced significantly by the molecular marker termed
      microsatellite instability and/or mismatch repair (MMR) gene product expression.1
      Study results and the National Comprehensive Cancer Network Colon Cancer
      Guideline panel suggest that adjuvant chemotherapy (fluoropyrimidine [5-FU] +/-
      oxaliplatin) be considered for patients with stage II colon adenocarcinoma
      harboring one or more "high-risk" features.2 However, for patients with deficient
      MMR (dMMR) stage II colon cancer, evidence suggests there may be a detrimental
      effect with adjuvant 5-FU alone.3 Finally, the addition of oxaliplatin to 5-FU
      does not appear to benefit older patients with stage II colon cancer.4,5 For the
      patient described, the challenge involved how to advise an older patient with a
      dMMR stage II colon cancer and a high-risk feature. The identified lymphovascular
      invasion in the tumor implies that adjuvant chemotherapy with either 5-FU or
      capecitabine +/- oxaliplatin would be reasonable considerations. However, the
      dMMR status of the tumor suggests that 5-FU alone would be contraindicated, and
      her age suggests that a lack of benefit would be expected from oxaliplatin.

PMID- 30119913
TI  - Growth curves and their associated weight and height factors in children from
      birth to 4 years old in West Azerbaijan Province, northwest Iran.
AB  - BACKGROUND: Growth trajectory standards are important components that need to be
      monitored for suitable child growth. This study examined longitudinal data to
      identify the factors affecting growth trajectory standards of height and weight
      for infants. METHODS: This study included 566 neonates (286 boys and 280 girls)
      born in West Azerbaijan Province, northwest Iran, who were followed from birth to
      4 years of age. The subjects' weight and height were recorded at birth, 1, 2, 4,
      6, 9 months and 1, 1.5, 2, 3, and 4 years of age. In this study, the Lambda-Mu
      Sigma (LMS) method was used to construct the growth curves for each measure. The
      linear mixed model was employed to determine the factors affecting the growth
      trajectory. RESULTS: The study demonstrates that the place of birth, duration of
      breastfeeding, and infants' gender had a significant effect on the growth
      trajectory. Nonetheless, other variables did not have any significant effect on
      growth. Growth curves for significant factors of weight and height (5th, 50th,
      95th percentiles) were obtained. There was a rapid increase in the growth curve
      from birth to 2 years of age, which then remained relatively constant up to 4
      years of age. DISCUSSION: This paper provides the first local growth trajectory
      standards of height and weight for infants by analyzing longitudinal measurements
      in West Azerbaijan province. This study determined the factors affecting the
      growth trend in both indices. It seems that there was a significant difference in
      the growth trajectories of infants in subgroups of the effective factor.

PMID- 30119914
TI  - Cost effectiveness and clinical efficacy of patent foramen ovale closure as
      compared to medical therapy in cryptogenic stroke patients: A detailed cost
      analysis and meta-analysis of randomized controlled trials.
AB  - BACKGROUND: Up to half the patients with cryptogenic stroke under the age of 55
      years have been found to have a PFO. Observational studies have demonstrated a
      benefit from closure of PFO and several RCTs have shown a trend toward benefit.
      The cost and clinical effectiveness of PFO closure is unclear. METHODS AND
      RESULTS: We searched for RCTs of PFO closure in patients with cryptogenic stroke
      and performed a detailed cost analysis and meta-analysis of treatment outcomes
      based on the results of the meta-analysis. Five RCTs containing 3404 patients
      with cryptogenic stroke were included. Of these 1829 underwent PFO closure and
      1611 received medical therapy. Mean follow-up was 4.0 years. PFO closure achieved
      cost effectiveness (<$50,000/Quality-adjusted life-year gained) 2.7 years (95%
      Confidence Interval (CI) 2.2-3.4) after closure. The incremental cost to prevent
      one combined end point (CEP, combined transient ischemic attack (TIA), stroke,
      and death) by PFO closure was $535,655(95% CI $458,329-$642,674). After 55.4
      years (95%CI 51.1-60.5) of follow-up, the per patient total cost of medical
      therapy exceeded that of PFO closure. PFO closure demonstrated clinical efficacy
      with a decreased risk of CEP (pooled hazard ratio (HR = 0.43(95%CI 0.27-0.59)))
      and a decreased risk of stroke (HR = 0.29(95%CI 0.02-0.57)). CONCLUSIONS: In
      comparison to medical therapy alone, PFO closure appears to be cost-effective and
      clinically efficacious.

PMID- 30119915
TI  - Ethnic and sex differences in ambulance activation among hospitalized patients
      with acute coronary syndromes: Insights from the Alberta contemporary acute
      coronary syndrome patients invasive treatment strategies (COAPT) study.
AB  - BACKGROUND: With acute coronary syndromes (ACS), activation of emergency medical
      services (EMS) ensures early treatment. However, EMS activation remains under
      utilized. We examined whether ground EMS use varied by sex or ethnicity among a
      population-based cohort of ACS patients. METHODS: We used linked administrative
      health datasets to identify patients who were hospitalized with an ACS (April 1,
      2002-March 31, 2016). Validated naming algorithms were used to categorize
      patients according to ethnicity (Caucasian, South Asian, Chinese). RESULTS: Of
      the 60,717 patients with an ACS (male: 41,175; female: 19,542), 42.3% presented
      to hospital via ground ambulance. Compared to males, females were more likely to
      activate EMS (38.9% vs. 49.3%, p < 0.001). Compared to the Caucasians (n =
      58,666), EMS activation was significantly higher among Chinese (n = 793) (42.1%
      vs. 49.8%; p = 0.0007) and slightly higher in South Asians (n = 1258) (42.1% vs.
      44.7%; p = 0.45). The relatively higher EMS use among females was maintained
      across the ethnic groups. In multivariable adjusted analyses, females were more
      likely to use EMS compared to males (OR: 1.31; 95% CI: 1.26-1.36). Compared to
      the Caucasians, a weaker trend towards South Asian and Chinese EMS activation was
      observed (OR: 1.08; 95% CI 0.96-1.21; OR: 1.10; 95% CI 0.95-1.28, respectively).
      In the male cohort only, South Asians and Chinese tended to activate EMS more
      often than the Caucasians (Males: South Asian OR: 1.14; 95% CI 1.00-1.31, Chinese
      OR: 1.15; 95% CI 0.96-1.38; Females: South Asian OR: 0.93; 95% CI 0.75-1.15,
      Chinese OR: 1.01; 95% CI 0.77-1.30). CONCLUSION: EMS use was sub-optimal and
      differed based on sex and ethnicity. Our results reinforce the need for targeted
      public health efforts to enhance ambulance activation.

PMID- 30119916
TI  - Long-Term Weight Loss and Metabolic Health in Adults Concerned With Maintaining
      or Losing Weight: Findings From NHANES.
AB  - More than two-thirds of American adults are overweight or obese, with many
      attempting to lose weight to avoid adverse health outcomes and improve well
      being. Achieving long-term weight loss (LTWL) success, defined as reaching at
      least a 5% to 10% weight loss goal, is challenging, yet important for overall
      metabolic health. It is currently unclear whether achieving higher thresholds of
      LTWL is associated with improved health. Therefore, the purpose of this study was
      to examine the association between LTWL thresholds (5%-9.9%, 10%-14.9%, 15%
      19.9%, >=20%) and metabolic health (metabolic syndrome and metabolic risk z
      score) among 7670 US adult respondents to the National Health and Nutrition
      Examination Survey (2007-2014) who were overweight or obese (past or present),
      were not underweight in the past year, not pregnant, and attempting to lose or
      maintain weight. A subsample of 3362 participants was used in the analysis of the
      metabolic risk z score. Multivariable regression models were constructed
      adjusting for covariates. Results indicate that the lowest and the 2 highest LTWL
      thresholds were related to lower odds for metabolic syndrome; for example,
      greater than or equal to 20% LTWL (odds ratio=0.52; 95% CI, 0.23-0.44; P<.001).
      All LTWL thresholds were significantly associated with the metabolic risk z
      score, with the largest effect among the 2 highest LTWL thresholds, that is, 15%
      to 19.9% LTWL (beta=-0.45; 95% CI, -0.54 to -0.36; P<.001) and greater than or
      equal to 20% LTWL (beta=-0.35; 95% CI, -0.53 to -0.17; P<.001). In conclusion,
      although achieving the currently recommended LTWL target was related to improved
      metabolic health, the 15% LTWL threshold was associated with more favorable
      outcomes.

PMID- 30119917
TI  - Corrigendum to "Genetic and environmental influences on pubertal hormones in
      human hair across development" [Psychoneuroendocrinology 90 (2018) 76-84].

PMID- 30119918
TI  - Ocean warming and acidification affect the nutritional quality of the
      commercially-harvested turbinid snail Turbo militaris.
AB  - Rising levels of atmospheric carbon dioxide are driving ocean warming and
      acidification. This could cause stress resulting in decreases in nutritional
      quality of marine species for human consumption, if environmental changes go
      beyond the optimal range for harvested species. To evaluate this, we used ambient
      and near-future elevated temperatures and pCO2 to assess impacts on the proximate
      nutritional composition (moisture, ash, protein, and lipids), fatty acids and
      trace elements of the foot tissue of Turbo militaris, a commercially harvested
      marine snail from south-eastern Australia. In a fully orthogonal design, the
      snails were exposed to ambient seawater conditions (22 +/- 0.2  degrees C, pH
      8.13 +/- 0.01-450 MUatm pCO2), ocean warming (25 +/- 0.05  degrees C), pCO2 ocean
      acidification (pH 7.85 +/- 0.02, ~880 MUatm pCO2) or a combination of both in
      controlled flow-through seawater mesocosms for 38 days. Moisture, ash, protein
      and total lipid content of the foot tissue in the turban snails was unaffected by
      ocean warming or acidification. However, ocean warming caused a reduction in
      healthful polyunsaturated fatty acids (PUFA) relative to saturated fatty acids
      (SFA). Under future warming and acidification conditions, there was a significant
      3-5% decrease in n-3 fatty acids, which contributed to a decrease in the n-3/n-6
      fatty acid ratio. The decrease in n-3 PUFAs, particularly Eicopentanoic acid
      (EPA), is a major negative outcome from ocean warming, because higher n-3/n-6
      ratios in seafood are desirable for human health. Furthermore, ocean warming was
      found to increase levels of zinc in the tissues. Calcium, iron, macroelements,
      microelements and the composition of toxic elements did not appear to be affected
      by ocean climate change. Overall, the major impact from ocean climate change on
      seafood quality is likely to be a decrease in healthy polyunsaturated fatty acids
      at higher temperatures.

PMID- 30119919
TI  - Effect of substrate deployment timing and reproductive strategy on patterns in
      invasiveness of the colonial ascidian Didemnum vexillum.
AB  - The colonial ascidian Didemnum vexillum is a high-profile marine invader, with a
      geographically widespread distribution after introductions to several temperate
      regions. D. vexillum has been the focus of several eradication and control
      programmes globally and the need for specific biological knowledge that relates
      to establishment processes, persistence, impacts and potential for spread
      remains. The present study describes temporal patterns of D. vexillum percent
      cover on experimental substrates over 1.5-years in relation to seasonality of
      substratum availability, in conjunction with key physical (i.e. temperature and
      sedimentation) and biological factors (i.e. interspecific competition) at two
      sites in New Zealand. Colonies showed large fluctuations in percent cover between
      the two study sites and with reference to timing of bare substratum availability.
      Colonies generally exhibited an initial lag phase, with peak levels of D.
      vexillum cover reached during the second summer or autumn post-deployment. The
      long-term competitive dominance of colonies founded from the reattachment of
      fragments, as opposed to ambient larval recruitment alone, was also investigated.
      Increases in colony size as a result of ambient recruitment alone were initially
      much slower. However, after 12-months colony cover exceeded that of plates
      inoculated with fragments, suggesting the benefit of the apparent competitive
      dominance conferred by fragment inoculation is restricted to the early
      establishment phase. This information will provide increased understanding of the
      population dynamics of this species, as well as assist in the implementation of
      effective management strategies through knowledge of environmental drivers of
      prolific infestations.

PMID- 30119920
TI  - Multifactorial etiology for tolerance to Deep Brain Stimulation for "essential
      tremor syndrome".

PMID- 30119921
TI  - Partnerships between students, academics and clinicians in co-creating the
      student experience.

PMID- 30119922
TI  - Changing attitudes towards healthy food via self-association or nutritional
      information: What works best?
AB  - Individual attitudes, both implicit and explicit, have been identified as one of
      the multiple drivers of consumer behaviors, including food-related ones. Building
      on such evidence, in this contribution we seek at increasing implicit and
      explicit consumer attitudes towards a healthy food, comparing the effectiveness
      of two different treatments. The former is based on a self-association task, that
      aims at inducing changes in the evaluation of an object thanks to its positive
      association with the self. The latter is based on information provision. We test
      if attitude formation can be moderated by the individual level of nutritional
      knowledge and health-concern. Additionally, we explored whether the study
      conditions applied could ultimately affect consumers' preferences for specific
      product attributes using a Discrete Choice Experiment. The main findings provide
      insights for future policy strategies aimed at promoting more healthful food
      consumption. Indeed, the self-association increased implicit attitudes and
      consumer preferences' towards healthy food, whereas information, that represents
      the main target of food policy interventions, seems to have no impact on
      individual attitudes and choice behaviors.

PMID- 30119923
TI  - Preclinical immunogenicity and protective efficacy of an oral Helicobacter pylori
      inactivated whole cell vaccine and multiple mutant cholera toxin: A novel and non
      toxic mucosal adjuvant.
AB  - Mucosal vaccines against Helicobacter pylori consisting of either whole cell
      bacteria or recombinant antigens can induce immune protection against challenge
      in mice only when co-administrated with a strong mucosal adjuvant such as cholera
      toxin (CT) or Escherichia coli heat labile enterotoxin (LT). The strong
      enterotoxicity of these adjuvants however preclude their use in human vaccines.
      The recently developed multiple mutant CT (mmCT) is a strong, yet practically non
      toxic novel mucosal adjuvant which here was admixed with a formalin-inactivated
      H. pylori whole cell vaccine (WCV) as a potential vaccine candidate against H.
      pylori infection. We report that intragastric immunizations with H. pylori WCV
      together with mmCT, similar to immunization with WCV together with CT, resulted
      in 50-125-fold reduction in colonization of H. pylori in the stomach of mice
      associated with rises in both serum IgG and intestinal-mucosal IgA anti-H. pylori
      antibody responses and strong T cell and IFNgamma and IL-17A cytokine responses.
      Data presented in this study also supports that the proposed vaccine can be grown
      in a bioreactor and would be effective against infection caused by a multitude of
      pathogenic H. pylori strains isolated from patients from various continents. The
      results warrant immunization studies in humans to evaluate the safety,
      immunogenicity and efficacy of the proposed H. pylori WCV and mmCT.

PMID- 30119924
TI  - Common and distinct patterns of abnormal cortical gyrification in major
      depression and borderline personality disorder.
AB  - Abnormal gray matter volume has been consistently reported in patients with major
      depressive disorder (MDD), but markers of cortical neurodevelopment have been
      rarely investigated. Also, it is unclear whether there exist common versus
      distinct spatial patterns of abnormal cortical development across different
      disorders presenting with negative emotions and deficient affective regulation.
      In this study, we used structural MRI at 3T to investigate the local gyrification
      index (LGI), a marker of fetal/infant neurodevelopment, in adult female patients
      with MDD (n = 22), in adult female patients with borderline personality disorder
      (BPD) (n = 17), and in controls (n = 22). Reduced cortical folding of the
      precuneus, the superior parietal gyrus and the parahippocampal gyrus was found in
      both MDD and BPD patients when compared to controls (p < 0.05, cluster-wise
      probability [CWP] corrected). MDD patients showed additional hypogyrification of
      the middle frontal gyrus and the fusiform gyrus when compared to both controls
      and BPD patients (p < 0.05, CWP corrected). In MDD patients, lower LGI of
      prefrontal regions was significantly associated with the age of disease onset and
      with the number of depressive episodes. In BPD patients, lower LGI of
      orbitofrontal regions was associated with impulsivity. Our findings suggest
      abnormal early cortical development in MDD, affecting brain regions that have
      been frequently implied in MDD pathophysiology. However, LGI abnormalities may
      not be specific for MDD, since MDD and BPD patients also exhibited common
      patterns of hypogyrification. Hypogyrification of cortical regions associated
      with higher-order cognition appears to be most pronounced in MDD. Abnormal early
      cortical neurodevelopment may mediate vulnerability to disorders of emotion.

PMID- 30119926
TI  - A General Approach to Facial Palsy.
AB  - Management of facial palsy can be daunting. This article presents a conceptual
      framework for classification and therapeutic management of facial palsy.

PMID- 30119925
TI  - Adjuvant treatment patterns and outcomes in patients with stage IB-IIIA non-small
      cell lung cancer in France, Germany, and the United Kingdom based on the LuCaBIS
      burden of illness study.
AB  - OBJECTIVES: To inform health-technology assessments of new adjuvant treatments,
      we describe treatment patterns in patients with complete resection of stage IB
      IIIA non-small cell lung cancer (NSCLC) in France, Germany, and the United
      Kingdom (UK). MATERIALS AND METHODS: Data were collected via medical record
      abstraction. Patients were aged >=18 years with completely resected stage IB-IIIA
      NSCLC, diagnosed between 01 January 2009 and 31 December 2011. Median follow-up
      was 26 months. Adjuvant treatment patterns and clinical outcomes were summarized
      descriptively. RESULTS: Among the 831 patients studied, 239 (29%) had stage IB
      disease, 179 (22%) had stage IIA disease, 165 (20%) had stage IIB disease, and
      248 (30%) had stage IIIA disease. Adjuvant systemic therapy was received by 402
      patients (48.4%), (France, 61.8%; Germany, 51.9%; UK, 33.4%). Use of adjuvant
      therapy increased with increasing stage of disease. Cisplatin/vinorelbine and
      carboplatin/vinorelbine were the most frequently prescribed adjuvant regimens.
      Median disease-free survival was 48.0 months (95% confidence interval [CI] 42.3
      not estimable); the 25th percentile was 13.2 months (95% CI, 11.0-15.3). 204
      patients (24%) died during the follow-up period. The median overall survival was
      not reached, the 25th percentile was 31.2 months (95% CI 26.8-36.0 months). 272
      patients (33%) had disease recurrence during the follow-up period. For 86 of
      those patients, the first recurrence was local or regional with no distant
      metastasis and 14 had further progression to metastatic disease during the follow
      up time. For the other 186 patients, the first recurrence involved distant
      metastases. A total of 200 patients had metastatic disease at any time during
      study follow-up. CONCLUSIONS: Less than half the patients with stage IB-IIIA
      NSCLC in this observational study received adjuvant systemic therapy. A high rate
      of first recurrence with distant metastatic disease was observed, emphasising the
      need for more effective systemic adjuvant therapies in this population.

PMID- 30119927
TI  - Gastric antral vascular ectasia in portal hypertensive children: Endoscopic band
      ligation versus argon plasma coagulation.
AB  - BACKGROUND/PURPOSE: Gastric antral vascular ectasia (GAVE) can cause recurrent
      bleeding and chronic anemia in children with portal hypertension (PHT). We aimed
      to evaluate the efficacy of EBL in comparison to argon plasma coagulation (APC)
      in children with PHT, bleeding from GAVE. METHODS: This prospective comparative
      study included 40 children with PHT who presented with nonvariceal GIT bleeding
      from GAVE. Patients were divided into 2 groups, each including 20 cases: one
      group was managed with APC and the other with EBL. Endoscopy was repeated every 3
      4 weeks until complete ablation of GAVE. Patients were reevaluated earlier in the
      event of recurrence of bleeding or in case of severe anemia necessitating blood
      transfusion. A follow-up endoscopy was done 6 months after the last APC or EBL
      session. RESULTS: The ages ranged between 2 and 16 years. The EBL group required
      a significantly lower number of sessions for complete obliteration of the lesions
      (1.85 +/- 0.81) as compared to APC group (4.15 +/- 1.22), p < 0.05. EBL was
      superior to APC as regards shorter procedure time (p = 0.001), lower blood
      transfusion requirement (p < 0.05), less hospitalization (p < 0.05) and
      significantly lower recurrence rate of GAVE after 6 months of follow up (p =
      0.01) CONCLUSIONS: EBL is more effective and time saving when compared to APC in
      treatment of bleeding from GAVE in children. LEVELS OF EVIDENCE: Treatment study,
      Level II (prospective comparative study).

PMID- 30119929
TI  - The controlled study of diffuse idiopathic skeletal hyperostosis for the
      assessment of physical function in elderly populations.
AB  - BACKGROUND: Diffuse idiopathic skeletal hyperostosis (DISH) is associated with
      increasing age, obesity, and diabetes mellitus. However, little is known about
      the clinical impacts of DISH on physical function and spinal deformity in elderly
      populations. The purpose of this study was to elucidate the influence of DISH on
      physical function, spinal deformity, and health-related quality of life (HRQOL)
      in elderly populations. METHODS: We enrolled 504 volunteers (203 men and 301
      women, mean age 74.0 years). Height, weight, body mass index (BMI), blood
      pressure, grip strength, one-leg standing time, sit-and-reach, functional reach,
      and bone mineral density (BMD) were measured. Using whole spine standing X-rays,
      the prevalence, location, and numbers of fused vertebra of DISH and spinopelvic
      parameters were measured. HRQOL measures, including the Oswestry Disability Index
      and the EuroQuol-5D were also obtained. We compared DISH subjects with control
      subjects of age and sex matching. We compared DISH subjects in the thoracic spine
      (T-DISH) to those in the thoraco-lumbar spine (TL-DISH). RESULTS: DISH occurred
      more frequently in men (14.3%) than in women (4.3%). The mean age was
      significantly higher of subjects with DISH than of those without DISH. The mean
      number of fused vertebra by DISH was 5.5 +/- 1.5, and T-DISH was observed in 57%
      cases. DISH group showed greater body weights, BMIs, blood pressures, and BMD in
      the lumbar spine compared to the control group. No inter-group differences were
      observed in physical function, HRQOL and spinopelvic parameters. Subjects with TL
      DISH had significantly lower values of sit-and-reach and functional reach than
      those with T-DISH. CONCLUSIONS: Subjects with DISH showed greater body weights,
      BMIs, blood pressures, and BMD compared to age- and sex-matched controls, while
      physical function, spinal alignment, and HRQOL were comparable between groups.

PMID- 30119928
TI  - Association between time to surgery and 90-day mortality after hip fracture: A
      retrospective cohort study of 1734 cases.
AB  - BACKGROUND: It remains unclear whether early surgical intervention can reduce
      mortality after surgery in hip fracture patients. The aim of this study was to
      investigate the association between time from injury to surgery and mortality
      rate within 90 days after hip fracture surgery. METHODS: We retrospectively
      identified 1827 patients who underwent hip fracture surgery in a tertiary care
      center in Japan between April 2007 and March 2017. After applying exclusion
      criteria (patients with spontaneous fracture, multiple fractures, revision
      surgery, total hip arthroplasty, or a refusal to participate), 1734 patients were
      included. We extracted data concerning patients' age, race, sex, operative
      procedure, American Society of Anesthesiologists (ASA) score, days from injury to
      surgery (injury-surgery days), and days from admission to surgery (admission
      surgery days), which could affect 90-day mortality after surgery. Variables
      associated with 90-day mortality were determined using multivariate logistic
      regression analysis. RESULTS: The 90-day postoperative mortality rate was 3.5%
      (60 of 1734). Multivariable analysis showed that injury-surgery days were not
      associated with 90-day mortality (odds ratio [OR], 0.91; 95% confidence interval
      [CI], 0.80 to 1.05; P = 0.19), and that older age (OR, 1.06; 95% CI, 1.02 to
      1.10; P = 0.005), male sex (OR, 3.62; 95% CI, 1.86 to 7.03; P < 0.001) and high
      ASA score (OR, 2.10; 95% CI, 1.06 to 4.18; P = 0.034) significantly increased 90
      day mortality. In addition, admission-surgery days were not associated with 90
      day mortality (OR, 0.95; 95% CI, 0.83 to 1.09; P = 0.45). CONCLUSION: Our results
      demonstrated that time from injury to surgery was not associated with mortality
      within 90 days after surgery after adjusting for age, sex, operative procedure,
      and ASA score.

PMID- 30119930
TI  - Accuracy of the lateral cage placement under intraoperative C-arm fluoroscopy in
      oblique lateral interbody fusion.
AB  - BACKGROUND: In oblique lateral interbody fusion (OLIF), the lateral cage enters
      into the disc space obliquely, and is then turned to the true lateral direction
      to achieve a lateral lumbar interbody fusion. The OLIF cage is sometimes placed
      asymmetrically although it seemed to be placed accurately on intraoperative C-arm
      images. The present study aimed to investigate the accuracy of cage placement and
      its effect on the radiological outcome in OLIF. METHODS: This study involved a
      retrospective radiological analysis of 127 lateral cages in 75 consecutive OLIF
      patients. The cage deviations from the midline and cage obliquity were evaluated
      using three sets of images: (1) intraoperative C-arm fluoroscopy, (2)
      postoperative standing radiographs, and (3) postoperative computed tomography
      (CT). RESULTS: The mean cage deviation from the midline was measured as 2.5 +/-
      2.7 mm on intraoperative C-arm images, but was found to be more deviated on
      postoperative radiographs and CT (5.4 +/- 3.8 mm and 3.8 +/- 3.7 mm; P = 0.000
      and 0.005, respectively). The cage obliquity on the intraoperative lateral C-arm
      was minimal in 26 (20.5%) cases, mild in 69 (54.3%), and moderate in 32 (25.2%),
      but was found to be more obliquely on postoperative radiographs as minimal in 9
      (7.1%), mild in 55 (43.3%), and moderate in 63 (49.6%) (P < 0.001).
      Anterior/posterior disc heights, disc lordotic angle, fusion rate, and cage
      subsidence rate were not different according to cage obliquity (all P > 0.05).
      CONCLUSIONS: Cage deviation from the midline and obliquity is underestimated on
      intraoperative C-arm images in OLIF. Although minimal cage deviation and
      obliquity did not affect the radiological outcome, great care should be made for
      the orthogonal cage insertion.

PMID- 30119931
TI  - Immunomodulatory effects of mesenchymal stem cells on leukocytes with emphasis on
      neutrophils.
AB  - Mesenchymal stem cells (MSCs) are a population of multipotent cells with the
      ability of expansion and plastic-adherence in vitro. MSCs can differentiate into
      chondrocytes, osteocytes and adipocytes; they lack co-stimulatory molecules and
      have small amount of MHC-I that makes no immunogenicity. These characteristics
      are empowering MSCs' huge in vivo applications. In addition, MSCs possess the
      ability of regulating the immune responses in many diseases. Many studies have
      shown that MSCs have immunosuppressive as well as immunoenhancing properties such
      as inhibition of T-lymphocytes proliferation and cytokines production which lead
      to the balance of Th1 and Th2. Some other immunomodulatory features of MSCs are
      increasing suppressive capacity of Treg, reducing activity of B-lymphocytes and
      immunoglobulins secretion, inhibition of dendritic cells maturation and antigen
      presenting capacity, and inhibition of NK-cells activity. MSCs also exert
      inhibitory effects on neutrophil apoptosis and reduce reactive oxygen species
      production. The purpose of this paper is to focus on the MSCs' effects on immune
      cells, especially neutrophils.

PMID- 30119932
TI  - Identifying SYNE1 ataxia and extending the mutational spectrum in Korea.
AB  - INTRODUCTION: Recent advances in next generation sequencing technologies have
      uncovered the genetic background of various diseases. The mutations in the SYNE1
      gene was previously identified as a potential cause of pure cerebellar ataxia.
      Although autosomal recessive ataxias are slightly more frequent than autosomal
      dominant forms worldwide, autosomal recessive forms are extremely rare in Korea.
      In this study, we aimed to identify SYNE1-associated ataxia by whole exome
      sequencing in a Korean sample, and to review the prevalence of SYNE1 in non
      French-Canadians. METHODS: Patients with suspected cerebellar ataxia who visited
      movement disorders clinic from March 2014 to December 2017 were clinically
      screened. After excluding cases with acquired causes and common genetic causes in
      Korea, including spinocerebellar ataxia and dentatorubral-pallidoluysian atrophy,
      63 undiagnosed subjects were screened for SYNE1 mutations by next generation
      sequencing methods. RESULTS: We identified four novel mutations (one splicing,
      one truncating, and two missense mutations) distributed throughout the SYNE1 gene
      in two patients. The phenotype was mainly pure cerebellar ataxia in both cases.
      However, axonal neuropathy, mild frontal dysfunction, and autonomic dysfunction
      were also revealed. The age of disease onset was relatively late and the disease
      course was only mildly progressive. CONCLUSION: Our results indicate that SYNE1
      mutations are not an uncommon cause of recessive ataxia with additional clinical
      features in the Korean population. The results of this study should alert
      neurologists to request SYNE1 testing to aid the diagnosis of undetermined adult
      onset ataxia in Korean patients.

PMID- 30119933
TI  - Prevalence of pre-diagnostic symptoms did not differ between LRRK2-related, GBA
      related and idiopathic patients with Parkinson's disease.
AB  - INTRODUCTION: Glucocerebrosidase (GBA) mutations and leucine-rich repeat kinase 2
      (LRRK2) variants are the most common genetic risk factors for late-onset
      Parkinson's disease (PD). In this study, we aimed to investigate the differences
      in pre-diagnostic symptoms of PD associated with the variants. METHODS: The
      participants were recruited from 24 centers across China and genotyped for LRRK2
      G2385R and R1628P variants and GBA L444P mutation. Participants were surveyed
      with structural questionnaires for history of environmental exposure and living
      habits and interviewed to collect the time at onset of each symptoms before
      diagnosis. We compared the cumulative prevalence and manifestation pattern of
      symptoms between groups using multiple logistic regression, adjusting age and
      gender. RESULTS: Total 1799 PD patients were recruited, including 226 patients
      with LRRK2 G2385R or R1628P variant, 44 with GBA L444P mutation, three with both
      LRRK2 and GBA mutation, and 1526 idiopathic patients. The cumulative prevalence
      of non-motor and typical motor symptoms did not differ between groups before
      diagnosis (P > 0.05). The manifestation sequences of non-motor symptoms were
      indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic PD
      subjects, and followed the sequence of constipation, hyposmia, sleep disorders,
      anxiety and depression, sexual dysfunction, urinary incontinency, dizziness and
      cognition. Slightly higher prevalence of hypomimia and micrographia were detected
      in the GBA-carriers. CONCLUSIONS: The prevalence of pre-diagnostic symptoms is
      almost indistinguishable between the LRRK2-carriers, GBA-carriers, and idiopathic
      PD before diagnosis; the sequence of the manifestation of non-motor symptoms
      largely conforms to the Braak stage for both genetic-related and idiopathic late
      onset PD.

PMID- 30119934
TI  - Impact of Self-Efficacy on The Quality of Life of Children With Asthma and Their
      Caregivers.
AB  - INTRODUCTION: Health-related quality of life is an important outcome measurement
      in the monitoring of asthma control. Self-efficacy is a determinant of self
      management behaviors that can contribute to the improvement of asthma control and
      quality of life. Our objective was to analyze the relationship between self
      efficacy and quality of life in children with asthma and their caregivers.
      METHODS: We included 176 patients aged 6-14 years with asthma, and determined
      their level of self-efficacy according to three groups (low, medium and high
      levels). Each child and their main caregiver completed the PAQLQ and PACQLQ
      questionnaires, respectively. RESULTS: PAQLQ range=1-7: 5.61+/-1.11; PACQLQ
      range=1-7: 5.42+/-1.35; self-efficacy range=0-60: low level 28.44+/-4.58; average
      level 37.41+/-1.7, and high level 47.50+/-5.5. Significant differences were
      observed in quality of life according to low-medium vs. high levels of self
      efficacy. Specific related domains: PAQLQ emotions and PAQLQ symptoms with self
      efficacy in problem-solving skills related to asthma and treatment self-efficacy;
      PACQLQ emotions with self-efficacy in problem-solving skills related to asthma.
      CONCLUSIONS: A high level of self-efficacy is associated with a better quality of
      life for children and their caregivers. Based on these results, the measurement
      of self-efficacy could be incorporated in the assessment of educational
      interventions in self-management targeted at the quality of life of the patient
      and his or her family.

PMID- 30119936
TI  - Trends in Admission for Bronchiectasis in a Third-Level Hospital (2008-2017).

PMID- 30119935
TI  - Prognostic Value of Frequent Exacerbations in Bronchiectasis: The Relationship
      With Disease Severity.
AB  - INTRODUCTION: Bronchiectasis is a very heterogeneous disease but some homogeneous
      groups with similar clinical characteristics and prognosis have been identified.
      Exacerbations have been shown to have a negative impact on the natural history of
      bronchiectasis. The objective of this study was to identify the definition and
      characteristics of the "frequent exacerbator patient" with the best prognostic
      value and its relationship with the severity of bronchiectasis. METHODS: A
      historical cohort of 651 patients diagnosed with bronchiectasis was included.
      They had all received 5 years of follow-up since their radiological diagnosis.
      Exacerbation was defined as a worsening of the symptoms derived from
      bronchiectasis that required antibiotic treatment. The main outcome was all-cause
      mortality at the end of follow-up. RESULTS: The mean age was 48.2 (16) years
      (32.9% males). 39.8% had chronic infection by Pseudomonas aeruginosa. Mean BSI,
      FACED, and E-FACED were 7 (4.12), 2.36 (1.68), and 2.89 (2.03), respectively.
      There were 95 deaths during follow-up. The definition of the "frequent
      exacerbator patient" that presented the greatest predictive power for mortality
      was based on at least two exacerbations/year or one hospitalization/year (23.3%
      of patients; AUC-ROC: 0.75 [95% CI: 0.69-0.81]). Its predictive power was
      independent of the patient's initial severity. The clinical characteristics of
      the frequent exacerbator patient according to this definition varied according to
      the initial severity of bronchiectasis, presence of systemic inflammation, and
      treatment. CONCLUSIONS: The combination of two exacerbations or one
      hospitalization per year is the definition of frequent exacerbator patient that
      has the best predictive value of mortality independent of the initial severity of
      bronchiectasis.

PMID- 30119937
TI  - Validation of new online game-based executive function tasks for children.
AB  - Numerous tasks are available to measure executive functions (EFs; working memory,
      inhibition, and flexibility) in children. However, they differ massively in the
      way they are presented and framed. Some contain child-friendly stimuli, feedback,
      or game elements likely to increase motivation and interest to perform the tasks,
      whereas others do not. Yet, it is unclear whether these apparent differences
      affect task performance. Therefore, the aim of our study was to develop and
      validate new game-based tasks assessing EFs in children. We designed three tasks
      for each dimension of EF and implemented them in a game version (based on the
      motivational framework proposed by Ryan and Deci (2000) and a standard version.
      The game-based tasks included elements designed to improve perceived competence
      (appealing feedback), autonomy (choosing how the protagonists proceed), and
      relatedness (a child-friendly cover story). To investigate whether adding these
      game elements influenced the motivation to engage in these tasks and task
      performance, 60 children (third and fourth graders) performed the game-based
      version and the standard version in two sessions (counterbalanced across
      participants). Because both the game-based and standard versions of the tasks
      should tap the same cognitive processes, we also tested whether performances in
      both versions were correlated. We found higher self-reported motivation in terms
      of interest, perceived competence, and relatedness after performing the game
      based version as compared with the standard version. Performance on the game
      based and standard versions of most of the tasks was significantly correlated,
      and there were no performance differences between the game-based and standard
      versions.

PMID- 30119938
TI  - Comparing the effects of organic, natural, and no additives labels on tobacco
      packaging between Lesbian, Gay, Bisexual (LGB) and heterosexual smokers.
AB  - INTRODUCTION: Previous research found that exposure to health-oriented language
      (e.g., natural, organic) on tobacco product packages is associated with reduced
      perceptions of harm and intention to purchase the product. However, how lesbian,
      gay, bisexual (LGB) individuals, who use tobacco products at a higher rate than
      heterosexual peers, respond to health-oriented labels has not yet been examined.
      This analysis examines whether responses to health-oriented labels differ between
      LGB persons and heterosexual individuals. METHODS: Secondary analysis was
      completed from an experimental study that exposed US adult smokers to a non-US
      cigarette (Study 1) or e-cigarette (Study 2) package that displayed either health
      oriented language ('100% organic,' 'all natural' or 'no additives'), traditional
      marketing language ('fine quality,' 'premium blend' or '100% original') or no
      language. RESULTS: No significant differences were found between LGB smokers and
      heterosexual smokers in responses to cigarette packages with health-oriented
      labels (Study 1). However, LGB smokers had less favorable attitudes toward the e
      cigarette product after viewing health-oriented labels (versus no language
      control label) while heterosexual smokers' attitudes did not differ across health
      oriented and control labels (Study 2). In addition, LGB smokers had lower
      intention to purchase and vape e-cigarettes, and less favorable attitudes in
      response to health-oriented labels than heterosexual smokers. CONCLUSIONS:
      Findings suggest that LGB smokers process pro-tobacco messages differently than
      heterosexual smokers, and that product type (i.e., cigarette vs. e-cigarette) may
      be a factor to consider. Further research is needed to uncover underlying
      mechanisms.

PMID- 30119940
TI  - Physical Restraint Use in Adult Patients Presenting to a General Emergency
      Department.
AB  - STUDY OBJECTIVE: The prevalence of agitation among emergency department (ED)
      patients is increasing. Physical restraints are routinely used to prevent self
      harm and to protect staff, but are associated with serious safety risks. To date,
      characterization of physical restraint use in the emergency setting has been
      limited. We thus aim to describe restraint patterns in the general ED to guide
      future investigation in the management of behavioral disorders. METHODS: We
      conducted a cross-sectional study of adult patients presenting to 5 adult EDs
      within a large regional health system for 2013 to 2015, and with a physical
      restraint order during their visit. We undertook descriptive analyses and cluster
      analysis to determine unique meaningful groups within our sample. RESULTS: In
      956,153 total ED visits, 4,661 patients (0.5%) had associated restraint orders,
      representing 3,739 unique patients. The median age was 47 years (interquartile
      range 32 to 59 years), 66.7% of patients were men, 61.9% had a psychiatric
      history, and 91.1% arrived by ambulance. For chief complaints, 33.7% were alcohol
      or drug use, 45.4% medical, 12.3% psychiatric, and 8.5% trauma. Cluster analysis
      identified 2 distinct cohorts. A younger, predominantly male population presented
      with alcohol or drug use, whereas an older group arrived with medical complaints.
      CONCLUSION: Our data found strong association of alcohol or drug use with
      physical restraints and identified a unique elderly population with behavioral
      disturbances in the ED. Further characterization of causal links and safer
      practices to manage agitation for these vulnerable populations are needed.

PMID- 30119939
TI  - Severely injured patients benefit from in-house attending trauma surgeons.
AB  - INTRODUCTION: There is continuous drive to optimize healthcare for the most
      severely injured patients. Although still under debate, a possible measure is to
      provide 24/7 in-house (IH) coverage by trauma surgeons. The aim of this study was
      to compare process-related outcomes for severely injured patients before and
      after transition of attendance policy from an out-of-hospital (OH) on-call
      attending trauma surgeon to an in-house attending trauma surgeon. METHODS:
      Retrospective before-and-after study using prospectively gathered data in a Level
      1 Trauma Center in the Netherlands. All trauma patients with an Injury Severity
      Score (ISS) >24 presenting to the emergency department for trauma before (2011
      2012) and after (2014-2016) introduction of IH attendings were included. Primary
      outcome measures were the process-related outcomes Emergency Department length of
      stay (ED-LOS) and time to first intervention. RESULTS: After implementation of IH
      trauma surgeons, ED-LOS decreased (p =  0.009). Time from the ED to the intensive
      care unit (ICU) for patients directly transferred to the ICU was significantly
      shorter with more than doubling of the percentage of patients that reached the
      ICU within an hour. The percentage of patients undergoing emergency surgery
      within 30 min nearly doubled as well, with a larger amount of patients undergoing
      CT imaging before emergency surgery. CONCLUSIONS: Introduction of a 24/7 in-house
      attending trauma surgeon led to improved process-related outcomes for the most
      severely injured patients. There is clear benefit of continuous presence of
      physicians with sufficient experience in trauma care in hospitals treating large
      numbers of severely injured patients.

PMID- 30119941
TI  - Randomized Controlled Trial of Intravenous Acetaminophen Versus Intravenous
      Hydromorphone for the Treatment of Acute Pain in the Emergency Department.
AB  - STUDY OBJECTIVE: As clinicians look to nonnarcotic analgesics in the emergency
      department (ED), it is essential to understand the effectiveness and adverse
      effects of nonopioid medications in comparison with existing opioid treatments.
      Studies of intravenous acetaminophen for acute pain in the ED demonstrate mixed
      results and suffer from small sample sizes and methodological limitations. This
      study compares intravenous hydromorphone with intravenous acetaminophen in adult
      ED patients presenting with acute pain. METHODS: This was a prospective,
      randomized, clinical trial comparing 1 g intravenous acetaminophen with 1 mg
      intravenous hydromorphone for treatment of adults with severe, acute pain in the
      ED. The primary outcome was between-group difference in change in numeric rating
      scale from baseline to 60 minutes postadministration of study medication.
      Secondary outcomes included the difference in proportion of patients in each
      group who declined additional analgesia at 60 minutes, received additional
      medication before 60 minutes, and developed nausea, vomiting, or pruritus.
      RESULTS: Of 220 subjects randomized, 103 patients in each arm had sufficient data
      for analysis. At 60 minutes, the mean decrease in numeric rating scale pain score
      was 5.3 in the hydromorphone arm and 3.3 in the acetaminophen arm, a difference
      of 2.0 (95% confidence interval [CI] 1.2 to 2.7) favoring hydromorphone. A
      greater proportion of patients in the hydromorphone arm also declined additional
      analgesia at 60 minutes (65% versus 44%; difference 21%; (95% CI 8% to 35%).
      There was no difference in the proportion of patients receiving rescue analgesia
      before 60 minutes. Significantly more subjects in the hydromorphone group
      developed nausea (19% versus 3%; difference 16%; 95% CI 4% to 28%) and vomiting
      (14% versus 3%; difference 11%; 95% CI 0% to 23%). CONCLUSION: Although both 1 mg
      intravenous hydromorphone and 1 g intravenous acetaminophen provided clinically
      meaningful reductions in pain scores, treatment with hydromorphone provided both
      clinically and statistically greater analgesia than acetaminophen, at the cost of
      a higher incidence of nausea and vomiting.

PMID- 30119942
TI  - Ultrarapid Rule-out for Acute Myocardial Infarction Using the Generation 5
      Cardiac Troponin T Assay: Results From the REACTION-US Study.
AB  - STUDY OBJECTIVE: We determine how well a new Food and Drug Administration
      approved single cardiac troponin T (cTnT) Generation 5 baseline measurement below
      the level of quantification (6 ng/L) and a novel study-derived baseline and 30
      minute cTnT Generation 5 algorithm might adequately exclude acute myocardial
      infarction in patients with suspected acute coronary syndrome in a US emergency
      department (ED). METHODS: Patients presenting with any symptoms suspicious for
      acute coronary syndrome were enrolled at a single US ED. Baseline and 30-minute
      blood samples were obtained and cTnT Generation 5 levels were later batch
      analyzed in an independent core laboratory. Acute myocardial infarction diagnosis
      was adjudicated by a cardiologist and an emergency physician. RESULTS: Of the 569
      study patients, 44 (7.7%) had an acute myocardial infarction diagnosis. One
      hundred sixty-four patients (28.8%) had a presentation cTnT Generation 5 level
      less than 6 ng/L, and none of these individuals had an acute myocardial
      infarction (negative predictive value of 100% [95% confidence interval 97.8% to
      100.0%] and sensitivity of 100% [95% confidence interval 92.0% to 100.0%]). A
      baseline cTnT Generation 5 value of less than 8 ng/L and a 30-minute Delta of
      less than 3 ng/L were present in 221 patients (41.0%), and none had acute
      myocardial infarction (negative predictive value of 100% [95% confidence interval
      98.3% to 100.0%] and sensitivity of 100% [95% confidence interval 92.0% to
      100.0%]). CONCLUSION: In a single US ED, a single baseline cTnT Generation 5
      measurement less than 6 mg/L and values at baseline less than 8 ng/L and a 30
      minute Delta of less than 3 ng/L ruled out acute myocardial infarction in 28.8%
      and 41.0% of patients, respectively. Additional multicenter US studies evaluating
      these ultrarapid acute myocardial infarction rule-out guidelines are needed,
      especially to narrow the confidence intervals.

PMID- 30119943
TI  - Ultrasonography for the Confirmation of Endotracheal Tube Intubation: A
      Systematic Review and Meta-Analysis.
AB  - STUDY OBJECTIVE: Intubation is routinely performed in the emergency department,
      and rapid, accurate confirmation is essential to avoid potentially serious
      adverse outcomes. The number of studies assessing ultrasonography for the
      verification of endotracheal tube placement has expanded rapidly in recent years.
      We performed this systematic review and meta-analysis to determine the
      sensitivity and specificity of transtracheal ultrasonography for the verification
      of endotracheal tube location. METHODS: PubMed, the Cumulative Index of Nursing
      and Allied Health, Scopus, Latin American and Caribbean Health Sciences
      Literature database, the Cochrane databases, and bibliographies of selected
      articles were assessed for all prospective and randomized controlled trials
      evaluating the accuracy of transtracheal ultrasonography for identifying
      endotracheal tube location. Data were dual extracted into a predefined worksheet
      and quality analysis was performed with the Quality Assessment of Diagnostic
      Accuracy Studies-2 tool. Data were summarized and a meta-analysis was performed
      with subgroup analyses by location, specialty, experience, transducer type, and
      technique. Time to confirmation was assessed as a secondary outcome. RESULTS:
      This systematic review identified 17 studies (n=1,595 patients). Overall,
      transtracheal ultrasonography was 98.7% sensitive (95% confidence interval [CI]
      97.8% to 99.2%) and 97.1% specific (95% CI 92.4% to 99.0%), with a positive
      likelihood ratio of 34.4 (95% CI 12.7 to 93.1) and a negative likelihood ratio of
      0.01 (95% CI 0.01 to 0.02). Subgroup analyses did not demonstrate a significant
      difference by location, provider specialty, provider experience, transducer type,
      or technique. Mean time to confirmation was 13.0 seconds. CONCLUSION:
      Transtracheal sonography is rapid to perform, with an acceptable degree of
      sensitivity and specificity for the confirmation of endotracheal intubation.
      Ultrasonography is a valuable adjunct and should be considered when quantitative
      capnography is unavailable or unreliable.

PMID- 30119944
TI  - Intervertebral disc calcification as a cause of painful torticollis in children.

PMID- 30119945
TI  - Echocardiographic indices of age- and gender-dependent cardiac remodeling over
      the adult lifespan in Irish Wolfhounds.
AB  - INTRODUCTION: Characterizing age- and gender-dependent cardiac remodeling over
      the adult lifespan in Irish Wolfhounds (IWs) by echocardiography. In people, a
      life-long cardiac remodeling process has been demonstrated. ANIMALS, MATERIALS,
      METHODS: Irish Wolfhounds (56 males, 90 females) with no indication of cardiac
      disease at final assessment (>7.0 years old). For each dog, four transthoracic
      echocardiographic studies were analyzed. Left ventricular (LV) systolic and
      diastolic internal dimensions (LVIDs, LVIDd), LV fractional shortening (FS) and
      ejection fraction (EF), LV free wall and interventricular septal thickness, right
      ventricular diastolic dimension, and left atrial (LA) and right atrial systolic
      diameters were compared at time points in the following age categories (years):
      1.0-2.5; 3.0-4.0; 4.5-6.0; and 7.0-10.5 and related to age, body weight, and
      heart rate. RESULTS: Over the adult life course, males had statistically
      significant increases in LV internal dimensions, atrial diameters, and decreases
      of FS and EF. From youngest to oldest age of examination means +/- standard
      deviations were as follows: LVIDs, 32.7 +/- 2.9 vs. 36.5 +/- 2.9 mm; LVIDd, 49.6
      +/- 4.7 vs. 53.4 +/- 3.8 mm; right atrial diameter, 36.8 +/- 3.3 vs. 42.6 +/- 3.3
      mm; LA, 49.0 +/- 3.6 vs. 55.0 +/- 3.7 mm; and FS, 34.6 +/- 3.7 vs. 31.0 +/- 3.2.
      In females, LV internal dimensions did not change significantly, increases in
      right atrial (38.1 +/- 3.7 mm to 40.0 +/- 5.2 mm) and LA diameter (48.8 +/- 3.6
      to 52.4 +/- 4.3 mm) were attenuated, as were decreases of FS (33.4 +/- 3.7 to
      31.5 +/- 4.4, p = 0.02). LV wall thicknesses did not significantly change in both
      genders. DISCUSSION AND CONCLUSIONS: Over the adult life course, echocardiography
      demonstrated increasing LV dimensions in male IWs only. In both genders, FS and
      EF decreased, and atrial diameters increased. Females showed an attenuated
      remodeling process.

PMID- 30119946
TI  - Mycobacterium tuberculosis: prePPARing and Maintaining the Replicative Niche.
AB  - Mycobacterium tuberculosis interferes with the ability of its host cell to
      undergo apoptosis. Arnett et al. report that the pathogen promotes macrophage
      survival by engaging the nuclear receptor PPARgamma to induce the antiapoptotic
      protein MCL-1, yielding insights into the pathogenesis of tuberculosis and
      potentially unlocking new avenues for therapeutic intervention.

PMID- 30119947
TI  - Acute hemolytic pancreatitis and hepatitis secondary to percutaneous
      pharmacomechanical thrombectomy of prosthetic vascular access for hemodialysis.

PMID- 30119949
TI  - Second victim: Malpractice disputes and quality of life among primary care
      physicians.
AB  - PURPOSE: The health of physicians can have a strong impact on the quality and
      safety of the health care they provide. Studies have shown a link between work
      stress, burnout, and depression. The aim of this study was to examine the
      association between malpractice dispute experiences and the well-being of
      physicians. METHODS: We conducted a cross-sectional survey to collect information
      about the malpractice experiences of primary care physicians in 2004. Data on
      sociodemographic and clinical characteristics and SF-36 measures were also
      collected. We used propensity score matching to estimate the association of
      medical malpractice experience with the general health, mental health, and
      vitality of physicians. RESULTS: Among the 1206 primary care physicians who
      completed the survey (response rate of 13.4%), 25.2% reported having ever
      experienced a malpractice dispute. After adjustment for baseline variables,
      physicians who had experienced a malpractice dispute had significantly worse
      health-related quality of life with regard to general health [-4.85; 95%
      confidence interval (CI), -7.61 to -1.80; P = 0.0016], mental health (-2.68; 95%
      CI, -5.03 to -0.34; P = 0.0252), and vitality (-3.28; 95% CI, -6.10 to -0.47; P =
      0.0224). The effects were particularly strong among physicians specializing in
      surgery or obstetrics and gynecology. CONCLUSIONS: The results reveal that a
      malpractice dispute can have a long-term negative effect on the health of
      physicians. Harm reduction programs for physicians involved in malpractice
      disputes should be implemented.

PMID- 30119948
TI  - Autologous stem cell transplantation in multiple myeloma: Post-transplant
      outcomes of Taiwan Blood and Marrow Transplantation Registry.
AB  - BACKGROUND/PURPOSE: Multiple myeloma (MM) is a monoclonal plasma cell malignancy.
      The primary choice of treatment for MM is induction therapy followed by
      autologous stem cell transplantation (ASCT). This study aimed to analyze the
      treatment efficacy of ASCT in a Taiwanese cohort and evaluate possible prognostic
      factors. METHODS: From the database of the Taiwan Blood and Marrow
      Transplantation registry, data on 396 patients with MM who underwent ASCT were
      reviewed. RESULTS: The average age of participants was 54.8 years, and there were
      more men than women (57.6% vs. 42.4%). Most patients were diagnosed with IgG-type
      myeloma (52.4%), followed by IgA-type (23.2%) and light-chain type (21.4%).
      Patients with Durie Salmon Staging System (DSS) III disease accounted for 61.9%
      of the study cohort, while 23.7% had stage II and 14.4% had stage I disease. The
      median progression-free survival (PFS) and overall survival (OS) after ASCT were
      46.5 months and 70.4 months, respectively. DSS III was a poor prognostic factor
      affecting both PFS and OS with a duration of 35.9 months and 69.0 months,
      respectively, compared with the other two stages (p = 0.006 and p = 0.03,
      respectively). In addition, patients with better treatment response before ASCT
      had better PFS and OS compared with those who did not show a response (both p <
      0.0001). The overall incidence of organ toxicities associated with
      transplantation was low. CONCLUSION: In conclusion, our cohort showed that
      myeloma patients with early DSS and better treatment response before ASCT had
      better long-term survival outcomes.

PMID- 30119950
TI  - Midwifery education from perspective of the WHO.

PMID- 30119951
TI  - Influence of Altered Auditory Feedback on Oral-Nasal Balance in Song.
AB  - OBJECTIVES: This study explored the role of auditory feedback in the regulation
      of oral-nasal balance in singing in trained singers and non-singers. STUDY
      DESIGN: Experimental repeated measures study. METHODS: Twenty non-singers
      (10M/10F) and 10 female professional singers sang a musical stimulus repeatedly
      while hearing themselves over headphones. Over the course of the experiment, the
      nasal level signal in the headphones was increased or decreased so that the
      participants heard themselves as more or less nasal. Nasalance scores in the
      different phases of the experiment were quantified using a Nasometer 6450.
      RESULTS: A repeated measures analysis of variance demonstrated a significant main
      effect for singing condition F(5, 135) = 3.70, P < 0.05, and multiple comparison
      tests demonstrated that the nasalance scores for final baseline and the maximum
      and minimum nasal feedback conditions were all significantly lower than the first
      baseline (all comparisons P < 0.05). CONCLUSION: There were no differences
      between the singers and non-singers. All participants had lower nasalance scores
      in response to both increased and decreased nasal signal level feedback.

PMID- 30119952
TI  - Improved Mucosal Wave in Unilateral Autologous Temporal Fascia Graft in Sulcus
      Vocalis Type 2 and Vocal Scars.
AB  - OBJECTIVES/HYPOTHESIS: We analyzed the results of 10 patients treated by
      unilateral autologous temporal fascia graft, comparing the pre and post surgery
      results, as well as the appearance of the wave and the intervals until the re
      appearance of it. STUDY DESIGN: Retrospective, clinical case series. METHODS:
      Subjective and objective evaluation was preoperatively and postoperatively
      performed, using laryngovideostroboscopy, the Voice Handicap Index-10, GRBAS
      (grade, roughness, breathiness, asthenia, and strain), harmonics to noise ratio,
      Jitter, Shimmer, phonatory range, maximum phonation time, and S/Z ratio in all
      patients. Postoperative visits were scheduled after 1 week, 1 month, at 3 months,
      and at 6 months after the surgery. RESULTS: After surgery, we found significant
      differences in the maximum phonation time and the S/Z ratio (P <0.05). Most
      parameters of GRBAS also improved significantly, both in general and in the
      subscales, except for Breathiness and Asthenia (P <0.05). There was an average
      decrease in Voice Handicap Index-10 of 11.2 (P <0.05). At
      laryngovideostroboscopy, the mucous wave reappeared in all patients treated 1
      month after surgery, and increased in amplitude until 6 months postoperative.

PMID- 30119953
TI  - Three-Dimensional Kinematic Analysis of the Distal Radioulnar Joint in the Axial
      Loaded Extended Wrist Position.
AB  - PURPOSE: To assess the wrist joints of healthy volunteers in extended and loaded
      states versus the unloaded state by using computed tomography (CT) to analyze the
      in vivo 3-dimensional movements in the distal radioulnar joint (DRUJ). METHODS:
      The dominant arms of 9 volunteers with healthy wrists were studied. We mounted a
      compression device onto the elbows in an inverted position. A 0-kg and 7-kg load
      each was applied during low-dose radiation CT imaging and a bone model was
      produced. We marked the insertion sites for the 4 radioulnar ligaments
      stabilizing the DRUJ: palmar superficial radioulnar ligament (PS-RUL), dorsal
      superficial radioulnar ligament (DS-RUL), dorsal deep radioulnar ligament (DD
      RUL), and palmar deep radioulnar ligament (PD-RUL). Using Marai's method, each
      ligament was virtualized and the length of each simulated ligament was measured.
      We also computed the 3-dimensional displacement and corresponding rotation of the
      distal ulna where it comes into contact with the radius in the sigmoid notch.
      RESULTS: The lengths of palmar ligaments (PS-RUL and PD-RUL) increased
      significantly under loaded conditions, and although not significant, the length
      of dorsal ligaments (DS-RUL and DD-RUL) tended to increase. When the wrist was
      loaded, the ulna rotated toward the open palmar side. CONCLUSIONS: The length of
      simulated radioulnar ligaments increased when the wrist joint was loaded in an
      extended position. This kinematic movement of DRUJ separation under a loading
      condition is different from physiological active movement. CLINICAL RELEVANCE:
      The 3-dimensional kinematic analysis revealed that palmar radioulnar ligaments
      were stretched during axial loading, suggesting that a tear of the palmer
      ligament can result from a fall on an outstretched hand.

PMID- 30119955
TI  - Stevens-Johnson Syndrome and Treatment With Clopidogrel.

PMID- 30119954
TI  - Consensus Document of the SEMI, semFYC, SEN, and SEC on Focused Cardiac
      Ultrasound in Spain.
AB  - This document summarizes the concept of focused cardiac ultrasound, the basic
      technical aspects related to this technique, and its diagnostic objectives. It
      also defines training requisites in focused cardiac ultrasound. This consensus
      document has been endorsed by the Spanish Society of Internal Medicine (SEMI),
      the Spanish Society of Family and Community Medicine (semFYC), the Spanish
      Society of Neurology (SEN), and the Spanish Society of Cardiology (SEC).

PMID- 30119956
TI  - Suboptimal bone status for adolescents with low motor competence and
      developmental coordination disorder-It's sex specific.
AB  - BACKGROUND: Australian adolescents with low motor competence (LMC) have higher
      fracture rates and poorer bone health compared to European normative data, but
      currently no normative data exists for Australians. AIMS: To examine whether
      there were bone health differences in Australian adolescents with LMC or
      Developmental Coordination Disorder (DCD) when compared to typically developing
      age-matched Australian adolescents. METHODS AND PROCEDURES: Australian
      adolescents aged 12-18 years with LMC/DCD (n = 39; male = 27; female = 12) and an
      Australian comparison sample (n = 188; boys = 101; girls = 87) undertook radial
      and tibial peripheral Quantitative Computed Tomography (pQCT) scans. Stress
      Strain Index (SSI (mm3)), Total Bone Area (TBA (mm2)), Muscle Density (MuD
      [mgcm3]), Muscle Area (MuA [cm2]), Subcutaneous Fat Area (ScFA [cm2]), Cortical
      Density (CoD [mgcm3]), Cortical Area (CoD [mm2]), cortical concentric ring
      volumetric densities, Functional Muscle Bone Unit Index (FMBU: (SSI/bone length))
      and Robustness Index (SSI/bone length^3), group and sex differences were
      examined. OUTCOME AND RESULTS: The main finding was a significant sex-x-group
      interaction for Tibial FMBU (p = .021), Radial MuD (p = .036), and radial ScFA (p
      = .002). Boys with LMC/DCD had lower tibial FMBU scores, radial MuD and higher
      ScFA than the typically developing age-matched sample. CONCLUSION AND
      IMPLICATIONS: Comparisons of bone measures with Australian comparative data are
      similar to European findings however sex differences were found in the present
      study. Australian adolescent boys with LMC/DCD had less robust bones compared to
      their well-coordinated Australian peers, whereas there were no differences
      between groups for girls. These differences may be due to lower levels of
      habitual weight-bearing physical activity, which may be more distinct in
      adolescent boys with LMC/DCD compared to girls.

PMID- 30119957
TI  - Design, synthesis and evaluation of oxime-functionalized nitrofuranylamides as
      novel antitubercular agents.
AB  - A series of oxime-functionalized nitrofuranylamides were designed, synthesized
      and evaluated for their in vitro anti-mycobacterial activities against MTB H37Rv
      and drug-resistant clinical isolates. Among them, two compounds 7a and 7b
      exhibited excellent activity against the three tested strains. Both of them were
      comparable to the first-line anti-TB agents INH and RIF against MTB H37Rv, and
      were far more potent than INH and RIF against MDR-TB 16833 and 16995 strains.
      Thus, both of them could act as leads for further optimization.

PMID- 30119958
TI  - Corrigendum to "A cascade synthesis, in vitro cholinesterases inhibitory activity
      and docking studies of novel Tacrine-pyranopyrazole derivatives" [Bioorg. Med.
      Chem. Lett. 28 (14) (2018) 2481-2484].

PMID- 30119959
TI  - A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant,
      and hepatoprotective effects.
AB  - Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity
      of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with
      hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid
      derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular
      hybridization. CF-HT exhibited significant hypolipidemia, reducing serum
      triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%,
      and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown
      hepatoprotective effect, a significant decrease in hepatic indices toxicity was
      observed, i.e. aspartate and lactate transaminases (AST and ALT) activities,
      alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight
      and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was
      significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA)
      content were remarkably restored. The hepatic glutathione (GSH) content was
      obviously increased and hepatic oxidized glutathione (GSSG) content was reduced
      dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover,
      the histopathological damage that hepatocyte hyperplasia and hypertrophy was also
      significantly ameliorated by treatment with CF-HT. Therefore, the results
      indicated that CF-HT exerted more potent hypolipidemic activity and definite
      hepatoprotective effect which may mainly be associated with its antioxidative
      property in mice.

PMID- 30119960
TI  - [Bicolour placenta: An illustration of the twin to twin transfusion syndrome].

PMID- 30119961
TI  - [First case of ocular rhinosporidiosis in French Guiana].

PMID- 30119962
TI  - [A cutaneous case of angiolymphoid hyperplasia with eosinophilia: Presentation of
      a rare entity].
AB  - We report the case of a Caucasian 73-year-old woman, without medical history, who
      is operated of two lesions of the forehead and the scalp measuring 0.4 and 1cm.
      There is no adenopathy. Histopathological examination revealed a diffuse vascular
      proliferation of the dermis and the hypodermis composed of small vessels bordered
      of plump "epthelioid" endothelial cells. There is no mitotic figure. The stroma
      is slightly fibrous accompanied by a polymorphic inflammatory infiltrate rich in
      lymphocytes, sometimes arranged in lymphoid follicles, plasma cells and
      eosinophils. The proposed diagnosis is angiolymphoid hyperplasia with
      eosinophilia. This is a rare vascular tumor, benign according with the OMS
      classification and preferentially observed in the skin. We report a cutaneous
      case, clinical and histopathological data of the reported cases and present the
      main differential diagnoses.

PMID- 30119964
TI  - Management of delayed stenosis of pancreatico-enteric anastomosis following
      pancreatoduodenectomy.
AB  - Stenosis of the pancreatico-enteric anastomosis following pancreatoduodenectomy
      (PD), a late post-operative complication that is seen mainly after PD for
      diseases with good prognosis, has been reported in less than 3% of cases in the
      literature. Most often asymptomatic, pancreatic-enteric anastomotic stenosis can
      lead to pancreatitis, pain or pancreatic insufficiency. Symptomatic stenosis is
      difficult to treat and its management is not standardized. Magnetic resonance
      cholangiopancreatography is the best investigation to confirm the diagnosis of
      stenosis. The Endoscopic UltraSonography (EUS) " rendezvous " technique,
      associating an endoscopic approach and EUS-guided puncture of the main pancreatic
      duct, has been available since 2010. Of note, however, the failure rate of the
      EUS series is as high as 25%, leading to repeat procedures. Surgical
      reconstruction of the anastomosis has been reported with good results in terms of
      morbidity. Surgical re-do of the pancreatico-enteric anastomosis for stenosis
      following PD carries a low risk of pancreatic fistula (around 5%) and an overall
      morbidity rate of around 20%.

PMID- 30119963
TI  - Polyphyllin I inhibits growth and invasion of cisplatin-resistant gastric cancer
      cells by partially inhibiting CIP2A/PP2A/Akt signaling axis.
AB  - The aberrant expression of cancerous inhibitor of protein phosphatase 2A (CIP2A)
      indicates poor prognosis and promotes EMT and metastasis. EMT, a crucial cellular
      process that occurs during cancer progression and metastasis, has been reported
      to promote drug resistance in several previous studies. Consequently, ongoing
      research has been focused on exploring therapeutic options for preventing EMT to
      delay or reverse drug resistance. Polyphyllin I (PPI) is a natural component
      extracted from Paris polyphylla that displays anti-cancer properties. In the
      present study, we investigated whether PPI can be used in the cisplatin (DDP)
      resistant human gastric cancer cell line SGC7901/DDP. The results demonstrated
      that PPI treatment significantly inhibited cell proliferation, invasion and EMT.
      TGF-beta1 is known to promote EMT-induced metastasis in numerous tumor types. PPI
      inhibited the invasion of TGFbeta1-induced SGC7901/DDP cells in vitro. PPI also
      increased the mRNA and protein expression levels of E-cadherin but decreased the
      expression levels of vimentin. Further examination of the mechanism revealed that
      the CIP2A/PP2A/Akt pathway is partially involved in this regulation of EMT
      related biomarkers and invasion. Furthermore, xenograft tests also confirmed the
      antitumor effects of PPI in vivo. We propose that PPI could be developed as a
      candidate drug for treating cancer invasion and migration.

PMID- 30119965
TI  - Imaging the heart to detect cardiomyopathy in Duchenne muscular dystrophy: A
      review.
AB  - Duchenne Muscular Dystrophy is the most common paediatric neuromuscular disorder.
      Mutations in the DMD gene on the X-chromosome result in progressive skeletal
      muscle weakness as the main clinical manifestation. However, cardiac muscle is
      also affected, with cardiomyopathy becoming an increasingly recognised cause of
      morbidity, and now the leading cause of mortality in this group. The diagnosis of
      cardiomyopathy has often been made late due to technical limitations in
      transthoracic echocardiograms and delayed symptomatology in less mobile patients.
      Increasingly, evidence supports earlier pharmacological intervention in
      cardiomyopathy to improve outcomes. However, the optimal timing of initiation
      remains uncertain, and the benefits of prophylactic therapy are unproven. Current
      treatment guidelines suggest initiation of therapy once cardiac dysfunction is
      detected. This review focuses on new and evolving techniques for earlier
      detection of Duchenne muscular dystrophy-associated cardiomyopathy. Transthoracic
      echocardiography or cardiac magnetic resonance imaging performed under
      physiological stress (dobutamine or exercise), can unmask early cardiac
      dysfunction. Cardiac magnetic resonance imaging can define cardiac function with
      greater accuracy and reliability than an echocardiogram, and is not limited by
      body habitus. Improved imaging techniques, used in a timely fashion, offer the
      potential for early detection of cardiomyopathy and improved long-term outcomes.

PMID- 30119966
TI  - Alcohol consumption during pregnancy and risk of small-for-gestational-age
      newborn.
AB  - BACKGROUND: Contradictory results have been published on the association of
      alcohol consumption during pregnancy with perinatal outcomes, including the risk
      of small for gestational age newborn. AIM: To determine whether alcohol
      consumption during pregnancy is associated with the risk of small for gestational
      age newborn. METHOD: A case-control study with 518 pairs of pregnant Spanish
      women in five hospitals was conducted; cases were women with small for
      gestational age newborn and age-matched (+/-2years) controls were women with non
      small for gestational age newborn. Data were gathered on demographic
      characteristics, socioeconomic status, toxic habits, and diet. Alcohol intake was
      recorded with a self-administered 137 food frequency questionnaire and with a
      personal interview, Alcohol intake was categorized -. Agreement in alcohol intake
      results between direct interview and frequency food questionnaire was evaluated
      with the Kappa index. Crude and adjusted odds ratios and their 95% confidence
      intervals were estimated by conditional logistic regression. FINDINGS: Poor
      agreement was observed between food frequency questionnaire and personal
      interview results for both cases (kappa=0.23) and controls (kappa=0.14). A food
      frequency questionnaire-recorded intake of less than 4g/day was associated with a
      significantly lower odds ratios for small for gestational age newborn (odds
      ratios=0.62, 95% confidence intervals, 0.43-0.88), whereas an interview-recorded
      intake of <4g/day was not related to small for gestational age newborn (odds
      ratios=0.86, 95% confidence intervals, 0.49-1.54). CONCLUSIONS: A very moderate
      alcohol intake during pregnancy may have a negative association with the risk of
      having a small for gestational age newborn.

PMID- 30119967
TI  - Gastric adenocarcinoma: Should pancreaticoduodenectomy be associated with
      intraoperative suspicion of infiltration?

PMID- 30119968
TI  - Prevalence of HLA-DQ2 and DQ8 haplotypes that predispose to celiac disease in
      Mexico.

PMID- 30119969
TI  - Incidence of second tumours in high risk prostate cancer patients according to
      the primary treatment applied.
AB  - INTRODUCTION AND OBJECTIVES: The onset of second primary tumours should be
      considered in high-risk prostate cancer patients in the natural course of the
      disease. Our aim was to evaluate the influence of primary treatment with curative
      intent for these patients on the development of second primary tumours. MATERIAL
      AND METHODS: A retrospective study of 286 patients diagnosed between 1996 and
      2008, treated by radical prostatectomy (n=145) or radiotherapy and androgen
      blockade (n=141). The homogeneity of both series was analysed using the Chi
      squared test for the qualitative variables, and the Student's t-test for the
      quantitative variables. A multivariate Cox regression analysis was performed to
      assess whether the type of primary treatment influenced the development of second
      tumours. RESULTS: The median age was 66 years, and the median follow-up was 117.5
      months. At the end of follow-up, 60 patients (21%) had developed a second primary
      tumour. In the prostatectomy group it was located in the pelvis in 13 (9%) cases,
      and those treated with radiotherapy and hormonotherapy in 8 (5.7%) cases (P=.29).
      The most common organ sites were: colo-rectal in 17 (28.3%) patients, the lung in
      11 (18.3%), and the bladder in 6 (10%) patients. In the multivariable analysis,
      the risk of a second tumour doubled for those treated with radiotherapy and
      hormonotherapy (HR=2.41, 95%CI: 1.31-4.34, P=.005) compared to the patients
      treated by prostatectomy. Age and rescue radiotherapy did not behave as
      independent predictive factors. CONCLUSIONS: The onset of a second primary tumour
      was related with the primary treatment given; thus the risk for those treated
      with radiotherapy and androgen deprivation therapy more than doubled.

PMID- 30119970
TI  - L-arginine attenuates blood pressure and reverses the suppression of angiogenic
      risk factors in a rat model of preeclampsia.
AB  - This study investigated the effect of L-arginine on blood pressure, angiogenic
      factors and liver enzymes in pregnant rats administered L-NAME. Thirty-six female
      Sprague-Dawley rats weighing between 150-170 g were divided into 4 groups of the
      control (normal saline), L-NAME (50 mg/kg b.w. intraperitoneal injection from
      days 13-18 of pregnancy), L-NAME + L-arginine (50 mg/kg b.w. and 1 g/kg b.w of L
      arginine from days 13 to 18) and L-arginine (1 g/kg b.w administered orally from
      days 13 to 18). Urine samples were collected on day 18 of pregnancy and the
      animals were sacrificed on day 19 of pregnancy for blood pressure parameters,
      angiogenic and liver enzyme assays. L-NAME increased protein, albumin, systolic
      and diastolic blood pressure significantly when compared with control. This
      effect was reversed by L-arginine when co-administered with L-NAME (p < 0.05). No
      difference was found in the pulse pressure and heart rate in all the groups as
      well as ALP and ALT levels. However, AST levels were significantly decreased in L
      Arginine (L-Arg) administered rats when compared with control. VEGF and PIGF
      levels were decreased in the L-NAME administered rats, while this levels were
      increased in the L-NAME + L-Arg group and L-Arg group when compared with the L
      NAME alone group (p < 0.05). sVEGFR-1 level was increased in L-NAME administered
      rats when compared to control, while in the L-NAME + L-Arg group and L-Arg group
      the level of sVEGFR-1 was significantly decreased when compared to L-NAME alone
      group. This study showed that L-arginine supplementation in pregnancy reduced the
      preeclampsia-like symptoms exhibited by L-NAME in pregnant rats.

PMID- 30119971
TI  - Enhanced magnetic ionic liquid-based dispersive liquid-liquid microextraction of
      triazines and sulfonamides through a one-pot, pH-modulated approach.
AB  - In this study, an enhanced variant of magnetic ionic liquid (MIL)-based
      dispersive liquid-liquid microextraction is put forward. The procedure combines a
      water insoluble solid support and the [P66614+][Dy(III)(hfacac)4-] MIL, in a one
      pot, pH-modulated procedure for microextraction of triazines (TZs) and
      sulfonamides (SAs). The solid supporting material was mixed with the MIL to
      overcome difficulties concerning the weighing of MIL and to control the uniform
      dispersion of the MIL, rendering the whole extraction procedure more
      reproducible. The pH-modulation during extraction step makes possible the one-pot
      extraction of SAs and TZs, from a single sample, in 15 min. Overall, the new
      analytical method developed enjoys the benefits of sensitivity (limits of
      quantification: 0.034-0.091 MUg L-1) and precision (relative standard deviation:
      5.2-8.1%), while good recoveries (i.e., 89-101%) were achieved from lake water
      and effluent from a municipal wastewater treatment plant. Owing to all of the
      above, the new procedure can be used to determine the concentrations of SAs and
      TZs at levels below the maximum residue limits.

PMID- 30119972
TI  - Combination of dispersive solid phase extraction and deep eutectic solvent-based
      air-assisted liquid-liquid microextraction followed by gas chromatography-mass
      spectrometry as an efficient analytical method for the quantification of some
      tricyclic antidepressant drugs in biological fluids.
AB  - A dispersive solid phase extraction coupled with deep eutectic solvent-based air
      assisted liquid-liquid microextraction has been developed and applied to the
      extraction and preconcentration of some tricyclic antidepressant drugs in the
      human urine and plasma samples prior to their determination by gas chromatography
      mass spectrometry. In this method, a sorbent (C18) is first added into an
      alkaline aqueous sample and dispersed by vortexing. By this action, the analytes
      are adsorbed onto the sorbent. Then, the sorbent particles are isolated from the
      aqueous solution by centrifugation. Afterward, a deep eutectic solvent, prepared
      from choline chloride and 4-chlorophenol is used to desorb the analytes from the
      sorbent. Subsequently, the supernatant solution is removed and added into an
      alkaline deionized water placed into a test tube with a conical bottom. The
      resulting mixture is rapidly sucked into a glass syringe and then injected into
      the tube. This procedure is repeated for several times and a cloudy solution
      consisting of fine droplets of deep eutectic solvent dispersed into the aqueous
      phase is formed. After centrifuging the obtained cloudy solution, the tiny
      droplets of the extractant, containing the extracted analytes, settle at the
      bottom of the tube. Finally, an aliquot of the extractant is taken and injected
      into the separation system for quantitative analysis. Several significant factors
      affecting the performance of the proposed method are evaluated and optimized.
      Under optimum extraction conditions, the method shows low limits of detection in
      the ranges of 5-10, 8-15 and 32-60 ng L-1 in deionized water, urine, and plasma,
      respectively. Enrichment factors are observed to be between 325 to 385 in
      deionized water, 155 to 185 in urine, and 64 to 72 in plasma. Extraction
      recoveries are in the range of 65-77 (in deionized water), 62-74 (in urine), and
      64-72% (in plasma). The relative standard deviations of the proposed method are
      <= 6% for intra- (n = 6) and inter-day (n = 4) precisions at a concentration of
      200 ng L-1 of each analyte. Finally, the applicability of the introduced method
      is investigated by analyzing the selected drugs in different biological fluids.
      In the proposed method, for the first time, a deep eutectic solvent composed of
      safe, cheap, and biodegradable compounds was synthesized and used (at MUL-level)
      as an elution and extraction solvent, simultaneously which led to omit the
      consumption of toxic organic solvents. This represents a significant advantage in
      the era of green chemistry. In addition, the introduced method is sensitive,
      simple in operation, rapid, and efficient.

PMID- 30119973
TI  - Self-assembling covalent organic framework functionalized poly (styrene-divinyl
      benzene-glycidylmethacrylate) composite for the rapid extraction of non-steroidal
      anti-inflammatory drugs in wastewater.
AB  - The growing use of non-steroidal anti-inflammatory drugs (NSAIDs) has seriously
      affected human health and ecosystems, as a result, the World Health Organization
      (WHO) has regarded them as emerging contaminants. NSAID's polar nature and trace
      amount present in wastewater make their extraction and determination challenging
      in modern analytical science. Therefore, regarding the need, we herein report a
      rapid, sensitive and selective in-syringe solid-phase extraction (SPE) method
      coupled with ultrahigh performance liquid chromatography and UV detector for the
      determination of seven NSAIDs in environmental water samples. Specifically, the
      NSAIDs in water samples were directly extracted by using synthesized porous
      covalent organic framework functionalized poly (styrene-divinyl benzene
      glycidylmethacrylate) composite (COF@PS-GMA) without further cleanup procedures.
      The adsorption of NSAIDs on COF@PS-GMA sorbent was investigated by using
      adsorption isotherms and kinetic studies. Various parameters, including amount of
      sorbent, pH of the samples, the volume of desorption solvent, and desorption time
      that were involved in in-syringe SPE were optimized. Under the optimized
      conditions, good linearity was observed at 0.005-5.0 MUg mL-1 with method
      quantification limits (LOQs) estimated between 0.54-2.74 MUg L-1. The recoveries
      of the seven NSAIDs at the level of 0.5, 5.0 and 20.0 MUg L-1 were ranging from
      84.3% to 99.6%.

PMID- 30119974
TI  - Dispersive liquid-liquid microextraction followed by gas chromatography-mass
      spectrometry for the determination of pesticide residues in nutraceutical drops.
AB  - An economical and rapid method has been developed using dispersive liquid-liquid
      microextraction (DLLME) coupled with gas chromatography-mass spectrometry to
      extract and determine forty pesticides in nutraceutical drops containing alcohol.
      Parameters affecting the DLLME performance, such as solvent selection and volume
      of extractive and dispersive solvent, salt effect, pH, mixing type and extraction
      time, were studied. Tetrachloroethane was the selected extraction solvent.
      Ethanol contained in the sample was enriched by methanol to serve as dispersive
      solvent. The method was fully validated under the optimized extraction
      parameters. The recoveries of pesticides were between 70 and 120% with relative
      standard deviations less than 20%. The limits of detection ranged from 0.001 to
      0.910 MUg/L and the limits of quantification ranged from 0.004 to 3.003 MUg/L.
      The optimized method was employed for determination of pesticide residues in real
      samples of nutraceutical drops and herbal alcoholic beverages.

PMID- 30119976
TI  - Selective Screening of Fatty Acids Oxidation Defects and Organic Acidemias by
      Liquid Chromatography/tandem Mass Spectrometry Acylcarnitine Analysis in
      Brazilian Patients.
AB  - BACKGROUND: Inborn errors of metabolism (IEM) are diseases which can lead to
      accumulation of toxic metabolites in the organism. AIM OF THE STUDY: To
      investigate, by selective screening, mitochondrial fatty acid oxidation defects
      (FAOD) and organic acidemias in Brazilian individuals with clinical suspicion of
      IEM. METHODS: A total of 7,268 individuals, from different regions of Brazil, had
      whole blood samples impregnated on filter paper which were submitted to the
      acylcarnitines analysis by liquid chromatography/tandem mass spectrometry
      (LC/MS/MS) at the Medical Genetics Service of Hospital de Clinicas de Porto
      Alegre, Brazil, during July 2008-July 2016. RESULTS: Our results showed that 68
      patients (0.93%) were diagnosed with FAOD (19 cases) and organic acidemias (49
      cases). The most prevalent FAOD was multiple acyl CoA dehydrogenase deficiency
      (MADD), whereas glutaric type I and 3-OH-3-methylglutaric acidemias were the most
      frequent disorders of organic acid metabolism. Neurologic symptoms and metabolic
      acidosis were the most common clinical and laboratory features, whereas the
      average age of the patients at diagnosis was 2.3 years. CONCLUSIONS: Results
      demonstrated a high incidence of glutaric acidemia type I and 3-OH-3-
      methylglutaric acidemia in Brazil and an unexpectedly low incidence of FAOD,
      particularly medium-chain acyl-CoA dehydrogenase deficiency (MCADD).

PMID- 30119975
TI  - High-performance liquid chromatographic determination of 2-aminoethylphosphonic
      acid and 2-amino-3-phosphonopropionic acid in seawater matrix using precolumn
      fluorescence derivatization with o-phthalaldehyde-ethanethiol.
AB  - 2-Aminoethylphosphonic acid (2-AEP) and 2-amino-3-phosphonopropionic acid (2-AP3)
      are two types of abundant and ubiquitous naturally occurring phosphonates used as
      sources of phosphorus by many prokaryotic lineages. The potential utilization
      mechanism of 2-AEP and 2-AP3 in eukaryotic phytoplankton is currently under
      investigation. However, the lack of suitable analytical methods in saline samples
      are the limitation of such researches. Herein, a high-performance liquid
      chromatography (HPLC) method for monitoring 2-AEP and 2-AP3 using precolumn
      fluorescence derivatization with o-phthalaldehyde-ethanethiol (OPA-ET) in
      seawater matrix was developed. The derivatization procedure and HPLC conditions
      were carefully examined, which included optimization of the fluorescence
      excitation and emission wavelengths, the ammonium acetate concentration and pH of
      the mobile phase, the OPA-ET reagent content and composition and derivatization
      time. Because increasing salinity was observed to lower the derivatization
      efficiency, working standards were freshly prepared in artificial seawater with
      the same salinity as that of the samples for the quantification of 2-AEP and 2
      AP3. The developed HPLC method showed a wide linear response with high linearity
      (R2 > 0.999) and high repeatability at three concentration levels. The relative
      standard deviation was less than 4.1% for 2-AEP and less than 1.7% for 2-AP3 (n =
      7). The limits of detection for 2-AEP and 2-AP3 in artificial seawater matrix
      were both 12.0 MUg/L. The recoveries were 83.0-104% for 2-AEP and 72.6-98.6% for
      2-AP3 in different aqueous samples, including algal culture medium prepared with
      filtered seawater. These results indicated the matrix effect of this method was
      insignificant.

PMID- 30119977
TI  - Impact of miR-302b on Calcium-phosphorus Metabolism and Vascular Calcification of
      Rats with Chronic Renal Failure by Regulating BMP-2/Runx2/Osterix Signaling
      Pathway.
AB  - OBJECTIVE: To investigate how miR-302b affect the calcium-phosphorus metabolism
      and vascular calcification (VC) of rats with chronic renal failure (CRF) via the
      regulation of bone morphogentic proteins 2/Runt-related transcription factor
      3/Osterix (BMP-2/Runx2/Osterix) signaling pathway. METHODS: SD rats were selected
      to establish CRF rat models and assigned into Sham, CRF, CRF + miR-302b, and CRF
      + miR-NC groups. The biochemical indexes of rats were detected at 8th and 12th
      week. Besides, HE staining and Von Kossa staining were performed to monitor renal
      structural changes and VC respectively; and quantitative real-time PCR (qRT-PCR)
      and Western blotting to evaluate the expressions of miR-302b and BMP
      2/Runx2/Osterix signaling pathway separately. RESULTS: HE and Von Kossa staining
      showed evident vascular calcification in rats from CRF and CRF + miR-NC groups
      with a large number of black granules deposited in renal artery compared with
      Sham group, but was improved in rats in the CRF + miR-302b group compared to
      those in the CRF group. Besides, rats in the CRF group had elevated levels of
      Scr, BUN, P, Cys C, and PTH, as well as the mRNA and protein expression of BMP-2,
      Runx2, and Osterix, and reduced serum Ca and miR-302b levels in a time-dependent
      manner (all p <0.05), which was in a completely opposite tendency in the CRF +
      miR-302b group (all p <0.05). CONCLUSION: miR-302b may improve calcium-phosphorus
      metabolism, and inhibit VC to alleviate the condition of CRF rats possibly
      associated with the BMP-2/Runx2/Osterix pathway, opening a new idea for CRF
      therapy.

PMID- 30119978
TI  - Cardiometabolic Risk Indicators for Kidney Disease in Mexican Patients with Type
      2 Diabetes.
AB  - INTRODUCTION: Kidney disease is one of the main complications in the diabetic
      patient. Risk factors such as obesity, dyslipidemia, and hyperglycemia have been
      associated with increased urinary albumin excretion (UAE) and decreased
      glomerular filtration rates (GFR). However, the data are inconsistent. The
      objective of this study was to identify the primary risk factors associated with
      kidney disease in Mexican patients with type 2 diabetes. METHODS: A cross
      sectional study was done in 395 patients with type 2 diabetes from four primary
      care clinics. From fasting venous blood samples, the serum creatinine, glucose,
      glycated hemoglobin (HbA1c), and lipid profiles were measured. The diagnosis of
      diabetic kidney disease (DKD) was made by measuring GFR with the CKD-EPI
      equation, and the UAE from the first morning urination, according to the KDIGO
      2012 Guidelines. Weight and waist circumference (WC), as well as body composition
      through the method of bioimpedance, were measured. RESULTS: Fourteen percent of
      the study population was diagnosed with DKD. Higher age and higher triglyceride
      levels were associated with a greater risk of DKD (p <0.05). In a multivariate
      analysis, higher age (OR = 1.06, 95% CI 1.02-1.11), triglyceride level (OR = 2.4,
      95% CI 1.18-4.92), WC (OR = 1.09, 95% CI 1.03-1.15), and smoking (OR 2.6, 95% CI
      1.07-6.49) were associated to DKD. CONCLUSION: Higher triglyceride levels,
      greater WC, and smoking are risk factors associated to DKD. An early diagnosis
      and opportune treatment for several cardiometabolic risk factors associated to
      DKD and cardiovascular disease should be identified and treated.

PMID- 30119979
TI  - Endothelial Colony-forming Cells Attenuate Ventilator-induced Lung Injury in Rats
      with Acute Respiratory Distress Syndrome.
AB  - BACKGROUND: Mechanical ventilation (MV) can cause ventilator-induced lung injury
      (VILI). AIM OF THE STUDY: This study investigated whether endothelial colony
      forming cells (ECFC) could inhibit VILI in a rat model of acute respiratory
      distress syndrome (ARDS). METHODS: Male Wistar rats received the femoral artery
      and venous cannulation (sham group) or were injected intravenously with 500
      MUg/kg lipopolysaccharide to induce ARDS. The ARDS rats were subjected to MV.
      Immediately after the MV, the rats were randomized and injected intravenously
      with vehicle (ARDS group) or ECFC (ECFC group, n = 8 per group). The oxygen
      index, lung wet-to-dry weight (W/D) ratios, cytokine protein levels in serum or
      bronchoalveolar lavage fluid (BALF), neutrophil counts, neutrophil elastase and
      total protein levels in BALF, histology and cell apoptosis in the lung were
      detected. The protein levels of endothelin-1, inducible nitric oxide synthase
      (iNOS), endothelial NOS, matrix metalloproteinase (MMP)-9, Bax, Bcl-2, gelsolin,
      cleaved caspase-3, phosphorylated NF-kappaBp65 and myosin light chain (MLC) in
      the lung were analyzed. RESULTS: Compared with the ARDS group, treatment with
      ECFC significantly increased the oxygen index, and decreased the lung W/D ratios
      and injury, and the numbers of apoptotic cells in the lungs, neutrophils counts,
      total protein and elastase concentrations in BALF of rats. ECFC treatment
      significantly minimized the protein levels of pro-inflammatory cytokines in BALF
      and serum, but increased interleukin 10 in rats. Furthermore, ECFC treatment
      significantly reduced the protein levels of endothelin-1, iNOS, Bax, Gelsolin,
      MMP-9, cleaved caspase-3, phosphorylated NF-kappaBp65 and MLC, but enhanced eNOS
      and Bcl-2 in the lungs of rats. CONCLUSIONS: Therefore, ECFC attenuated
      inflammation, cell apoptosis and VILI in ARDS rats.

PMID- 30119980
TI  - Role of Response-to-Diuretic in Predicting Prognosis in Discharged Heart Failure
      Patients After an Acute Decompensation.
AB  - BACKGROUND: The diuretic response has been shown to be a robust independent
      marker of cardiovascular outcomes in acute heart failure (ADHF) patients. The
      objectives of this clinical research, will aim are to: a) include diuresis in the
      formula for diuretic response (R-to-D); b) add to R-to-D the value of a pre
      discharged determination of galectin-3 and BNP in predicting mid-term clinical
      outcome. METHODS: Consecutive patients discharged alive after an ADHF were
      enrolled. All patients underwent BNP and galectin-3, a 6 min walk test and an
      echocardiogram together with diuresis and body weight during diuretic
      administration. Death by any cause, cardiac transplantation and worsening HF
      requiring readmission to the hospital were considered cardiovascular events.
      RESULTS: 141 patients (98 males, age 73.8) were analysed (follow-up 17 months).
      During the follow-up 45 (31.9%) events were scheduled (19 cardiac deaths, 26 re
      hospitalisation for HF). Patients who experienced CV-event had a worst renal
      function (p = 0.003), an higher BNP (p = 0.006) and galectin-3 (p = 0.008). At
      multivariate analysis, only R-to-D, galectin-3 and BNP showed a significant
      correlation with worst clinical prognosis (respectively p = 0.043; OR 6.01; p =
      0.01; OR 8.9; p = 0.02 OR 10.38), independently of age and renal function. Kaplan
      Meier curves depicted a powerful stratification using an R-to-D <1.2 kg/40 mg
      furosemide (log rank 10.96; p = 0.0009). Adding R-to-D<1.2 mg/40 mg furosemide to
      galectin-3>17.6 pg/mL and BNP>500 pg/mL the predictive value improved (log rank
      23.59; p = 0.0001). CONCLUSION: Adding R-to-D to Gal-3 and BNP, a single pre
      discharge strategy testing seemed to obtain a satisfactorily predictive value in
      alive HF patients discharged after an ADHF episode.

PMID- 30119981
TI  - Data Mining and Endocrine Diseases: A New Way to Classify?
AB  - Data mining consists of using large database analysis to detect patterns,
      relationships and models in order to describe (or even predict) the appearance of
      a future event; to accomplish this, it uses classification methods, rules of
      association, regression patterns, link and cluster analyses. Recently this
      approach has been used to propose a new diabetes mellitus classification, using
      information analysis techniques through which the selection bias minimally
      influences categorization, this new focus that includes data mining previously
      implemented to predict, identify biomarkers, complications, therapies, health
      policies, genetic and environmental effects of this disease; it could be
      generalized in the field of endocrinology, in the classification of other
      endocrine diseases.

PMID- 30119983
TI  - The association between genetic risk score and blood pressure is modified by
      coffee consumption: Gene-diet interaction analysis in a population-based study.
AB  - BACKGROUND & AIM: Recent genome-wide association studies (GWAS) have identified
      single nucleotide polymorphisms (SNPs) that are associated with high blood
      pressure (BP). However, whether coffee consumption interacts with the genetic
      variants related to BP is yet unclear. Thus, this study aimed to investigate
      whether the association between genetic risk core (GRS) and blood pressure was
      modified by usual coffee consumption. METHODS: Data were from the 'Health Survey
      of Sao Paulo' a cross-sectional population-based survey, among 533 participants
      aged 20 years or older. Coffee consumption was estimated by two 24-h dietary
      recalls and categorized into <1, 1-3, and >3 cups/day. The GRS was calculated
      based on SNPs in previous GWAS [CYP1A1/CYP1A2 (rs2470893, rs2472297); CPLX3/ULK3
      (rs6495122); MTHFR (rs17367504)]. Multiple logistic regression analysis were
      performed to estimate the associations between GRS with high BP, and both, high
      systolic BP (SBP) and diastolic BP (DBP); and the multiplicative interaction term
      between the GRS and coffee consumption were tested by including in the models.
      RESULTS: Higher GRS independently contributed to higher probability of elevated
      BP, SBP and DBP in this population (OR = 1.85, 95%CI = 1.19-2.87; OR = 2.30,
      95%CI = 1.32-4.01 and OR = 1.66, 95%CI = 1.10-2.51; respectively). Moreover,
      there were a significant interaction effects for coffee consumption and GRS on
      the high BP, SBP and DBP. Individuals with higher BP increasing alleles in the
      GRS had a significantly high BP (OR = 5.09, 95%CI = 1.32-19.7), and both elevated
      SBP and DBP (OR = 2.14, 95%CI = 1.12-4.11; OR = 3.54, 95%CI = 1.17-10.75), among
      those with high coffee consumption (>3 cups coffee/day). CONCLUSIONS: Consumption
      of coffee could interact with genetic predisposition in relation to BP. Thus, the
      GRS for high BP is modified by coffee consumption. Individuals with greater GRS
      appeared to have high BP associated with higher coffee consumption, highlighting
      the particular importance to reduce coffee intake in individuals genetically
      predisposed to this cardiovascular disease risk factor.

PMID- 30119982
TI  - Evaluation of appendicular lean mass using bio impedance in persons aged 80+: A
      new equation based on the BUTTERFLY-study.
AB  - BACKGROUND: To date, the accuracy of bio-impedance (BIA) to assess body
      composition & sarcopenia in persons aged 80 and over remains unclear. OBJECTIVE:
      We aimed to evaluate the agreement between dual energy X-ray absorptiometry (DXA)
      and BIA equations to determine lean mass, as well as their suitability to
      identify sarcopenia. DESIGN: 174 community dwelling well-functioning persons (83
      women, 91 men) aged 80 and over were included. Appendicular lean mass (ALM) was
      predicted using BIA-based equations available in literature, and compared to DXA
      outcomes. Through cross-validation and stepwise multiple linear regression, a new
      ALM-formula was generated suitable for this population. RESULTS: Literature-based
      BIA equations systematically overestimated ALM. The new prediction formula that
      we propose for the 80+ is: ALM = 0,827+(0,19*Impedance
      Index)+(2,101*Sex)+(0,079*Weight); R2 = 0,888; SEE = 1,450 kg. Sarcopenia
      classification based on our new BIA equation for ALM showed better agreement with
      DXA (k >= 0,454) compared to literature-based BIA equations (k < 0,368).
      CONCLUSIONS: Despite the high correlation between both methods, literature-based
      BIA equations consistently overestimate ALM compared to DXA in persons aged 80
      and over. We proposed a new equation for ALM, reaching higher agreement with DXA
      and thus improving the accuracy of BIA for this specific age group.

PMID- 30119984
TI  - Development and application of a scoring system to rate malnutrition screening
      tools used in older adults in community and healthcare settings - A MaNuEL study.
AB  - RATIONALE: Many malnutrition screening tools are used to screen for risk of
      malnutrition in older adults. An aim of the Joint Programming Initiative (JPI) 'A
      Healthy Diet for a Healthy Life' (HDHL) MalNutrition in the ELderly Knowledge hub
      (MaNuEL) is to devise recommendations on the best tools to screen for risk of
      malnutrition in older adults in community and healthcare settings across Europe.
      The aim of this paper was to develop and apply a scoring system to rate
      malnutrition screening tools. METHODS: Using a targeted literature search
      strategy, 48 malnutrition screening tools used to screen for risk of malnutrition
      in older adults were identified across community, rehabilitation, residential
      care and hospital settings. Criteria to rate each tool were developed; these were
      based on published evidence and expert opinion. These criteria were translated
      into a scoring system. RESULTS: The scoring system had three equally weighted
      sections; validation, parameters and practicability, and was applied to all 48
      tools. Overall, the highest scoring tools per setting for screening for risk of
      malnutrition in older adults were i) DETERMINE your health checklist for the
      community setting; ii) the Nutritional Form for the Elderly (NUFFE) for the
      rehabilitation setting; iii) the Short Nutritional Assessment Questionnaire
      Residential Care (SNAQRC) for residential care and iv) both the Malnutrition
      Screening Tool (MST) and the Mini Nutritional Assessment Short Form Version 1
      (MNA-SF-V1) for the hospital setting. CONCLUSION: Setting-specific tools are more
      appropriate for use with older adults. These findings will inform recommendations
      for the optimal screening of geriatric malnutrition across Europe.

PMID- 30119985
TI  - Managing Nonmetastatic Castration-resistant Prostate Cancer.
AB  - CONTEXT: Patients with nonmetastatic castration-resistant prostate cancer
      (nmCRPC) have rising prostate-specific antigen (PSA) and castrate testosterone
      levels, with no radiological findings of metastatic disease on computed
      tomography and bone scan. Given recent drug approvals for nmCRPC, with many other
      therapeutics and imaging modalities being developed, management of nmCRPC is a
      rapidly evolving field that merits detailed investigation. OBJECTIVE: To review
      current nmCRPC management practices and identify opportunities for improving care
      of nmCRPC patients. EVIDENCE ACQUISITION: A literature search up to July 2018 was
      conducted, including clinical trials and clinical practice guidelines (National
      Comprehensive Cancer Network, European Society for Medical Oncology, European
      Association of Urology, Prostate Cancer Clinical Trials Working Group, Prostate
      Cancer Radiographic Assessments for Detection of Advanced Recurrence). Keywords
      included prostate cancer, nonmetastatic, castration resistance, rising PSA, and
      biochemical relapse. EVIDENCE SYNTHESIS: Recommendations regarding indications
      for, and frequency of, imaging and PSA testing, as well as for initiating
      systemic therapy in nmCRPC are based on PSA rise kinetics and symptoms. Both
      enzalutamide and apalutamide have been shown to significantly increase metastasis
      free survival in phase III placebo-controlled randomised trials in nmCRPC
      patients with PSA doubling time (DT) <=10 mo. The expected impact of new imaging
      techniques in the assessment of nmCRPC is also reviewed. CONCLUSIONS: nmCRPC is a
      heterogeneous disease; while observation may be an option for some patients,
      enzalutamide and apalutamide may be appropriate to treat nmCRPC patients with PSA
      DT <=10 mo. The emergence of more accurate imaging modalities as well as
      circulating tumour biomarker assays will likely redefine the assessment of nmCRPC
      in the near future. PATIENT SUMMARY: Herein, we review key literature and
      clinical practice guidelines to summarise the optimal management of patients with
      prostate cancer and rising prostate-specific antigen despite castrate
      testosterone levels, but with no evidence of distant metastasis on traditional
      imaging. New drugs are being developed for this disease setting; novel imaging
      and tumour biomarker blood tests are likely to define this disease state more
      accurately.

PMID- 30119986
TI  - Pyelonephritis treatment in the community emergency department: Cephalosporins
      vs. first-line agents.
AB  - OBJECTIVE: The purpose of this study was to assess treatment with a
      fluoroquinolone or trimethoprim-sulfamethoxazole versus cephalosporins for
      pyelonephritis in discharged patients from a community hospital setting. METHODS:
      A retrospective chart review was completed for adult female patients who received
      a prescription for a cephalosporin, fluoroquinolone or trimethoprim
      sulfamethoxazole for the treatment of pyelonephritis within the network of a
      large healthcare system. The primary endpoint evaluated the failure rate of each
      treatment group. The secondary endpoint evaluated the difference between rates of
      resistance on culture and sensitivity reports for treatment groups. RESULTS: A
      total of 55 patients in the cephalosporin group and 43 patients in the
      fluoroquinolone and trimethoprim-sulfamethoxazole group were reviewed. The
      primary endpoint occurred in 0% of the patients in the cephalosporin group and in
      23% of the patients in the fluoroquinolone and trimethoprim-sulfamethoxazole
      group, p < 0.001. Of the 98 urine samples collected, 71 samples were positive for
      pathogen growth. Upon evaluation of these isolates, 6% were resistant to
      cephalexin, 1% was resistant to cefdinir, 3% were resistant to ciprofloxacin and
      23% were resistant to trimethoprim-sulfamethoxazole. Trimethoprim
      sulfamethoxazole showed statistical significance for more bacterial resistance
      compared to the other agents, p < 0.01. CONCLUSION: Failure of therapy for
      pyelonephritis occurred more often in the fluoroquinolone and trimethoprim
      sulfamethoxazole group than in the cephalosporin group. The findings in this
      study are most applicable to patients who are treated on an outpatient basis. A
      prospective, randomized clinical trial is necessary to confirm these results.

PMID- 30119987
TI  - Suspected gonorrhea and chlamydia: Incidence and utilization of empiric
      antibiotics in a health system emergency department setting.
AB  - BACKGROUND: In the ED, patients are treated empirically for suspected gonorrhea
      and/or chlamydia (GC). Limited studies have evaluated the treatment of sexually
      transmitted diseases (STDs) in conjunction with predictor variables. This study
      will allow providers to better identify patients with potential GC to streamline
      antibiotic treatment. OBJECTIVES: The primary objective was to determine the
      incidence of positive assay in patients that underwent GC screening. The
      secondary objectives included the proportion of patients assayed that received
      empiric therapy and the predictive value of risk factors to identify positive
      assays. METHODS: This retrospective cohort study included adult patients who
      presented to the health-system EDs and underwent GC screening. Subjects were
      excluded if they were victims of sexual assault, left AMA or eloped. RESULTS: A
      total of 490 assayed patients were included, of which 84 (17%) were found to be
      positive for GC assay. Of the 278 patients treated empirically, 74% had a
      negative assay. Of the entire sample (n = 490), risk factors found to predict a
      positive assay (p < 0.05) included male, women <25 years of age, concomitant
      bacterial vaginosis, pelvic inflammatory disease or trichomonas, penile
      discharge, inconsistent condom use, previous/coexisting STDs, and uninsured.
      CONCLUSIONS: Compared to previous reports, this study found a higher incidence of
      positive GC assays for patients with suspected infection. This is the first study
      to evaluate GC testing in both men and women in the ED, and risk factors not
      previously reported by the CDC were identified.

PMID- 30119988
TI  - Urgent care peripheral nerve blocks for refractory trigeminal neuralgia.
AB  - OBJECTIVE: After medication failure, patients with refractory trigeminal
      neuralgia (TGN) often present urgently and seek more potent or invasive therapies
      such as opioids or surgical options. Peripheral nerve blocks, safe and simple,
      may offer extended pain relief prior to opioid use or more invasive ganglion
      level procedures. METHODS: We report a retrospective case-series (urgent care, at
      a large urban medical center, over a 2 year period) of nine patients with
      intractable primary TGN who underwent peripheral trigeminal nerve blocks after
      failing conservative medical therapy. After antiseptic skin preparation, a 30 g
      needle was inserted localizing to the supraorbital, infraorbital, and mental
      foramens. 0.5 mL of 0.25% bupivicaine:1% lidocaine was injected locally at all
      three foramens. Then, 1 mL of the above was injected in the region of the
      auriculotemporal nerve (see Video 1). All injections were done on the side with
      TGN pain. RESULTS: All nine patients experienced immediate pain relief of >50%
      with 7 of 9 being completely pain free or just mild paresthesia. Six of nine
      patients had lasting pain relief (1-8 months); three patients reporting pain now
      tolerable with adjunct medication and two patients were completely pain free.
      CONCLUSIONS: The treatment paradigm for TGN remains unclear when a patient fails
      conservative medical therapy. In this case series, many patients achieved rapid
      and sustained TGN pain relief with peripheral trigeminal nerve blocks. This
      modality should be considered as a potential therapeutic option in the ED or
      urgent care setting.

PMID- 30119989
TI  - Out-of-hospital cardiac arrest outcomes with "pit crew" resuscitation and
      scripted initiation of mechanical CPR.
AB  - OBJECTIVE: To compare OHCA outcomes in patients managed with mechanical versus
      manual CPR in an EMS system with a "pit crew" approach to resuscitation and a
      scripted sequence for the initiation of mechanical CPR. METHODS: Through a year
      long quality improvement effort we standardized the initial resuscitative efforts
      for OHCA, prioritizing a "pit crew" approach to high quality manual CPR, early
      defibrillation and basic airway management ahead of a scripted sequence for
      initiating mechanical CPR. We then analyzed outcomes for adult, non-traumatic
      OHCA attended in the following year (2016). We used a propensity score matched
      analysis to compare ROSC, survival to discharge, and neurologic status among
      patients managed with manual versus mechanical CPR while controlling for patient
      demographics and arrest characteristics. RESULTS: Of 444 eligible OHCAs, 217
      received manual and 227 received mechanical CPR. Crude ROSC (39.2% vs. 29.1%) and
      survival to discharge (13.8% vs. 5.7%) were higher with manual CPR. In the
      propensity matched analysis (n = 176 manual CPR; 176 mechanical CPR), both ROSC
      (38.6% vs. 28.4%; difference: 10.2%; CI: 0.4% to 20.0%) and survival to discharge
      (13.6% vs. 6.8%; difference: 6.8%; CI: 0.5% to 13.3%) remained significantly
      higher for patients receiving manual CPR. CONCLUSIONS: In this EMS system with a
      standardized, "pit crew" approach to OHCA that prioritized initial high-quality
      initial resuscitative efforts and scripted the sequence for initiating mechanical
      CPR, use of mechanical CPR was associated with decreased ROSC and decreased
      survival to discharge.

PMID- 30119990
TI  - Beyond Promoters: How Genes Tweak Their Own Expression.
AB  - The correct expression of genes is vital for cells to function. Schikora-Tamarit
      et al. show that, in addition to obeying their promoters, most genes can modulate
      their own expression by either buffering or amplification. This could help to
      avoid costly overexpression of proteins.

PMID- 30119991
TI  - Biotin-Thiamine-Responsive Basal Ganglia Disease-A Treatable Metabolic Disorder.

PMID- 30119992
TI  - The diagnostic value of Rosemont and Japanese diagnostic criteria for
      'indeterminate', 'suggestive', 'possible' and 'early' chronic pancreatitis.
AB  - BACKGROUND: Longitudinal data are lacking to support consensus criteria for
      diagnosing early chronic pancreatitis. METHODS: Retrospective single centre study
      of the initial evidence for chronic pancreatitis (CP), with reassessment after
      follow-up (January 2003-November 2016). RESULTS: 807 patients were previously
      diagnosed with chronic pancreatitis. This diagnosis was rejected in 118 patients:
      52 had another pathology altogether, the remaining 66 patients formed the study
      population. 38 patients with 'normal' imaging were reclassified as chronic
      abdominal pain syndrome (CAPS), and 28 patients had minimal change features of CP
      on EUS (MCEUS) but never progressed. Strict application of the Japanese
      diagnostic criteria would diagnose only two patients with early CP and eleven as
      possible CP. Patients were more likely to have MCEUS if the EUS was performed
      within 12 months of an attack of acute pancreatitis. 40 patients with MCEUS were
      identified, including an additional 12 who progressed to definite CP after a
      median of 30 (18.75-36.5) months. Those continuing to consume excess alcohol
      and/or continued smoking were significantly more likely to progress. Those who
      progressed were more likely to develop pancreatic exocrine insufficiency, require
      pancreatic surgery and had higher mortality. CONCLUSION: There needs to be more
      stringent application of the systems used for diagnosing chronic pancreatitis
      with revision of the current terminology 'indeterminate', 'suggestive',
      'possible', and 'early' chronic pancreatitis. All patients with MCEUS features of
      CP require ongoing clinical follow up of at least 30 months and all patients with
      these features should be strongly counselled regarding smoking cessation and
      abstinence from alcohol.

PMID- 30119994
TI  - In vitro and in vivo pharmacokinetic and pharmacodynamic study of MBRI-001, a
      deuterium-substituted plinabulin derivative as a potent anti-cancer agent.
AB  - MBRI-001 was demonstrated preliminary better pharmacokinetics and antitumor
      effects than that of plinabulin in vivo. In this approach, we further carried out
      systematic pharmacokinetic and pharmacodynamic study of MBRI-001 in vitro and in
      vivo. MBRI-001 was tested stable in rat plasma and more stable in liver
      microsomes than plinabulin in vitro. In vivo, MBRI-001 could be distributed
      rapidly and widely in various tissues, especially the concentration of MBRI-001
      in lung was remarkably higher than other tissues. Excretion study indicated that
      MBRI-001 might been decomposed and excreted as metabolites. Additionally, the
      combination treatment of MBRI-001 and gefitinib revealed better antitumor
      inhibition rate than monotherapy in vivo. Therefore, we suggest that MBRI-001
      could be developed as a promising anti-cancer agent in near future.

PMID- 30119993
TI  - Transketolase like 1 (TKTL1) expression alterations in prostate cancer
      tumorigenesis.
AB  - BACKGROUND: Prostate cancer (CaP) is the most common nonepidermal cancer in
      elderly males. Due to its heterogeneity and high variability in regards to
      clinical outcome and therapeutic response, urologists' handling of this disease
      remains a challenge. The objective of this study was to assess Transketolase like
      1 (TKTL1) expression in benign prostatic tissue, peritumoral tissue and in CaP
      (in different stages of disease), and its correlation with clinicopathological
      findings, in order to detect if TKTL1 expression is associated with CaP
      tumorigenesis. METHODS: In total, 100 tissue samples were included: (i) 22 benign
      specimens, (ii) 46 specimens with nonmetastatic CaP, and (iii) 32 specimens from
      patients with metastatic CaP. From the tissue microarray slides, we evaluated
      immunohistochemically the expression of the TKTL1 protein, using the H-score.
      RESULTS: The TKTL1 protein expression pattern ranges from a low level in benign
      prostatic tissue (100 [57.5-105]), moderately low in peritumoral tissue (135.42
      [100-195.16]), moderate expression in nonmetastatic CaP (200 [172.19-254.38]) to
      high in metastatic CaP (300 [222.50-300]). A significant rise of TKTL1 mean
      expression was seen throughout disease progression. A significant difference was
      also found in TKTL1 expression between peritumoral tissue and benign tissue.
      CONCLUSION: The results obtained in this study suggest that pentose phosphate
      pathway and its key enzyme TKTL1 is altered throughout the CaP tumorigenesis, and
      this pathway merits further investigation.

PMID- 30119995
TI  - Synthesis and bioactivities evaluation of l-pyroglutamic acid analogues from
      natural product lead.
AB  - A series of l-pyroglutamic acid analogues from natural product lead were designed
      and synthesized, as well as their antifungal activities against Phytophthora
      infestans, neuritogenic activities, antibacterial activities and anti
      inflammatory activities are described. The bioassays and SAR study showed that
      the majority of l-pyroglutamic acid esters have a significant antifungal activity
      against P. infestans, especially 2d and 2j demonstrated the best activities with
      EC50 values of 1.44 and 1.21 MUg mL-1, which were about seven times that of
      commercial azoxystrobin (7.85 MUg mL-1). Moreover, compounds 2e, 2g and 4d
      displayed anti-inflammatory activity against LPS-induced NO production in BV-2
      microglial cells; neuritogenic activity in NGF-induced PC-12 cells is the same
      activity. This study demonstrates that compounds 2d and 2j are potential drugs to
      control P. infestans.

PMID- 30119996
TI  - The Kinase IKKbeta Regulates a STING- and NF-kappaB-Dependent Antiviral Response
      Pathway in Drosophila.
AB  - Antiviral immunity in Drosophila involves RNA interference and poorly
      characterized inducible responses. Here, we showed that two components of the IMD
      pathway, the kinase dIKKbeta and the transcription factor Relish, were required
      to control infection by two picorna-like viruses. We identified a set of genes
      induced by viral infection and regulated by dIKKbeta and Relish, which included
      an ortholog of STING. We showed that dSTING participated in the control of
      infection by picorna-like viruses, acting upstream of dIKKbeta to regulate
      expression of Nazo, an antiviral factor. Our data reveal an antiviral function
      for STING in an animal model devoid of interferons and suggest an evolutionarily
      ancient role for this molecule in antiviral immunity.

PMID- 30119997
TI  - The Environmental Sensor AHR Protects from Inflammatory Damage by Maintaining
      Intestinal Stem Cell Homeostasis and Barrier Integrity.
AB  - The epithelium and immune compartment in the intestine are constantly exposed to
      a fluctuating external environment. Defective communication between these
      compartments at this barrier surface underlies susceptibility to infections and
      chronic inflammation. Environmental factors play a significant, but
      mechanistically poorly understood, role in intestinal homeostasis. We found that
      regeneration of intestinal epithelial cells (IECs) upon injury through infection
      or chemical insults was profoundly influenced by the environmental sensor aryl
      hydrocarbon receptor (AHR). IEC-specific deletion of Ahr resulted in failure to
      control C. rodentium infection due to unrestricted intestinal stem cell (ISC)
      proliferation and impaired differentiation, culminating in malignant
      transformation. AHR activation by dietary ligands restored barrier homeostasis,
      protected the stem cell niche, and prevented tumorigenesis via transcriptional
      regulation of of Rnf43 and Znrf3, E3 ubiquitin ligases that inhibit Wnt-beta
      catenin signaling and restrict ISC proliferation. Thus, activation of the AHR
      pathway in IECs guards the stem cell niche to maintain intestinal barrier
      integrity.

PMID- 30119998
TI  - Participation of hypoxia-inducible factor-1alpha and lymphangiogenesis in
      metastatic and non-metastatic lower lip squamous cell carcinoma.
AB  - This study evaluated the lymphatic density and HIF-1alpha immunoexpression in
      lower lip squamous cell carcinoma (LLSCC) and their correlation with
      clinicopathological (nodal metastasis, clinical stage, histological grade,
      recurrence and disease outcome) and survival parameters in 20 metastatic and 20
      non-metastatic LLSCCs. Lymphatic density was established by counting microvessels
      (D2-40+) at the tumor core (intratumoral lymphatic density, ILD) and at the
      invasive front (peritumoral lymphatic density, PLD) and percentages of
      immunopositive cells for HIF-1alpha were established. No statistically
      significant differences in lymphatic densities in relation to clinicopathological
      parameters were observed (P > 0.05). All cases exhibited nuclear and cytoplasmic
      HIF-1alpha immunoexpression, with relatively high percentages of positivity, but
      this expression was not statistically different in relation to
      clinicopathological variables (P > 0.05). Positive correlations were observed
      between ILD and PLD (P = 0.002), and between nuclear HIF-1alpha immunoexpression
      at the tumor core and ILD (P = 0.001). The results suggest ILD and PLD are not
      directly related to the development of lymph node metastasis in LLSCC. The
      striking expression of HIF-1alpha suggests the involvement of this protein in the
      etiopathogenesis of LLSCCs, possibly stimulating lymphangiogenesis at the tumor
      core. However, this protein does not seem to exert a determining influence on the
      biological aggressiveness of these tumors.

PMID- 30119999
TI  - Integration of Palliative Care and Oncology Nursing.
AB  - OBJECTIVE: To describe the evolution of oncology and palliative nursing in
      meeting the changing landscape of cancer care. DATA SOURCES: Peer-reviewed
      articles, clinical practice guidelines, professional organization, and position
      statements. CONCLUSION: Nurses have been at the forefront of efforts to develop
      and implement oncology and palliative care programs. Fifty years ago a cancer
      diagnosis meant a poor prognosis, high symptom burden, and disease uncertainty.
      Current cancer care has advanced to include palliative care in conjunction with
      innovative therapies and symptom management. IMPLICATIONS FOR NURSING PRACTICE:
      Specialty trained oncology and palliative care nurses are essential in disease
      and symptom management, psychosocial and spiritual support, and advance care
      planning.

PMID- 30120000
TI  - Evidence-based Palliative Care Approaches to Non-pain Physical Symptom Management
      in Cancer Patients.
AB  - OBJECTIVE: To review effective approaches for non-pain symptom management for
      cancer patients focusing on treatment of nausea and vomiting, constipation,
      diarrhea, anorexia/cachexia, fatigue, and dyspnea. DATA SOURCES: Peer-reviewed
      articles, clinical practice guidelines, professional organization position
      statements. CONCLUSION: Oncology nurses are key advocates for optimal symptom
      management. Maximizing palliation of symptoms improves quality of life and
      prolongs survival. IMPLICATIONS FOR NURSING PRACTICE: To provide an evidence
      based approach to symptom management, oncology nurses require a deep
      understanding of symptom pathophysiology while anticipating side effects,
      educating patients and caregivers, considering psychosocial/spiritual factors,
      exploring treatment expectations, and clarifying goals of treatment.

PMID- 30120001
TI  - Short-term outcomes after major hepatic resection in patients with cirrhosis: a
      75-case unicentric western experience.
AB  - BACKGROUND: The benefit of performing major hepatic resection (MHR) for
      hepatocellular carcinoma (HCC) in patients with cirrhosis remains controversial
      because of its high risk of posthepatectomy liver failure (PHLF). This study was
      conducted to assess the risk of MHR for HCC in patients with cirrhosis. METHODS:
      Patients with Child-Pugh A or B cirrhosis and HCC who underwent MHR from January
      2000 to June 2014 were retrospectively identified. Risk factors for postoperative
      morbidity and mortality using univariate and multivariate analyses were
      evaluated. RESULTS: Seventy patients with Child-Pugh A (93%) and 5 (7%) with
      Child-Pugh B cirrhosis underwent MHR for HCC. Thirteen (17%) had Barcelona Clinic
      Liver Cancer (BCLC) stage A, 39 (50%) had BCLC B, and 23 (32%) had BCLC C
      disease. A perioperative blood transfusion was performed in 18 patients (24%).
      Ninety-day postoperative mortality was 9% (n = 7). Major complications occurred
      in 16 patients (21%), including PHLF in 9 patients (12%). A multivariate analysis
      showed that perioperative blood transfusion was the main independent factor
      associated with mortality (OR = 6.5) and major morbidity (OR = 10). CONCLUSION:
      In selected patients with HCC and cirrhosis, MHR is feasible and has acceptable
      mortality, but careful perioperative management and limiting blood loss are
      required.

PMID- 30120003
TI  - In vitro anti-demodectic effects and terpinen-4-ol content of commercial eyelid
      cleansers.
AB  - PURPOSE: To compare the in vitro anti-demodectic activity of four commercially
      available dedicated eyelid cleansers (Cliradex(r) towelette cleanser, OustTM
      Demodex(r) cleanser, BlephadexTM eyelid foam, TheraTears(r) SteriLid(r) eyelid
      cleanser), tea tree oil, undiluted terpinen-4-ol and linalool; and to assess the
      terpinen-4-ol content of the commercial cleansers and tea tree oil. METHODS: In
      vitro anti-demodectic efficacy assessment: 93 viable Demodex mites were acquired
      from the epilated eyelashes of 10 participants, and were randomised to
      application with one of the four eyelid cleansers, 100% and 50% tea tree oil,
      undiluted terpinen-4-ol and linalool, or no treatment. Following treatment
      application, mite viability was assessed for 300 min, based on limb/body movement
      and/or the development of a crenated/translucent appearance. Kaplan-Meier
      survival analysis was then performed. MASS SPECTROMETRY ANALYSIS: The absolute
      concentration of terpinen-4-ol and the relative abundance of linalool in the four
      eyelid cleansers and tea tree oil were determined. RESULTS: In vitro anti
      demodectic efficacy assessment: No significant differences were observed between
      undiluted tea tree oil, terpinen-4-ol and linalool (all p > 0.05). Although all
      commercial eyelid cleansers effected lower mite survival probabilities than the
      untreated group, Cliradex(r) was the only eyelid cleanser that demonstrated
      comparable antiparastic activity to 50% tea tree oil (p = 0.36). MASS
      SPECTROMETRY ANALYSIS: Among the four eyelid cleansers, Cliradex(r) contained the
      highest concentration of terpinen-4-ol, while linalool was present in
      TheraTears(r) SteriLid(r) only. CONCLUSIONS: Of the four commercial eyelid
      cleansers, Cliradex(r) demonstrated the highest levels of in vitro anti
      demodectic activity and terpinen-4-ol content. Undiluted linalool and terpenin-4
      ol showed comparable antiparasitic efficacy, and the use of linalool in the
      management of demodectic blepharitis warrants further investigation.

PMID- 30120002
TI  - Survival, Complications and Patient Reported Outcomes after Pancreatic Surgery.
AB  - BACKGROUND: Long-term effects of complications in pancreatic surgery have not
      been systematically evaluated. The objectives were to assess potential effects of
      complications on survival and patient reported outcomes (PROs) as well as
      feasibility of PRO questionnaires in patients with periampullary and pancreatic
      tumors. METHODS: From October 2008 to December 2011, 208 patients undergoing
      pancreatic surgery were included in a prospective observational study. ESAS,
      EORTC QLQ-C30 and QLQ-PAN26 questionnaires were completed at inclusion, then
      every third month. Complications were recorded according to the Clavien-Dindo
      (CD) classification and Comprehensive Complication Index (CCI). RESULTS: 148
      complications were registered in 100 patients (48%), 36 patients (17%) had CD
      IIIa or above. 125 patients (60%) completed baseline questionnaires, 80 (39%)
      responded after three and 54 (28%) after six months. Complications were
      associated with reduced long-term survival in patients with pancreatic ductal
      adenocarcinoma (PDAC) (p = 0.049) and other malignant diseases. No significant
      relationship was found between complications and PROs, except for anxiety, which
      was significantly increased in patients with complications. CONCLUSION:
      Postoperative complications led to increased anxiety at 3 months after surgery
      and were associated with reduced long-term survival in patients with malignancy.
      A short, patient derived, disease specific questionnaire is required in the
      clinical research context.

PMID- 30120004
TI  - First results with a new intraocular lens design for the individual correction of
      spherical aberration.
AB  - PURPOSE: To assess the feasibility of individual compensation of corneal
      spherical aberration with a custom intraocular lens (IOL). SETTING: Department of
      Ophthalmology, Rudolf Virchow Klinikum Glauchau, Glauchau, Germany. DESIGN:
      Prospective case series. METHODS: Cataract patients were randomized to receive an
      individual aberration-correcting IOL (Invidua-aA; Group A) or a standard aspheric
      aberration-free IOL of otherwise identical design (Aspira-aA; Group B). In Group
      A, the IOL was designed according to preoperative calculation of the corneal
      spherical aberration Z(4,0). The aim was to achieve an overall postoperative
      ocular spherical aberration close to zero. Four weeks and 3 months
      postoperatively, the refraction, visual acuity (far, intermediate, and near
      distance), photopic and mesopic contrast sensitivities (with and without glare),
      defocus curve, corneal and ocular spherical aberration, and pupil size were
      measured. RESULTS: Group A, 57 eyes of 42 patients and Group B, 29 eyes of 27
      patients. Preoperatively, there was no difference in corneal spherical aberration
      between groups (P > .05). Three months postoperatively, residual ocular spherical
      aberration Z(4,0) was significantly lower in Group A (P < .001). Photopic and
      mesopic contrast sensitivities (with and without glare) were significantly higher
      in Group A at most spatial frequencies. Monocular defocus curve and distance,
      intermediate, and near visual acuity outcomes did not differ significantly
      between groups. CONCLUSIONS: Implantation of a custom monofocal aspheric IOL
      effectively reduced overall ocular spherical aberration. Clinical outcomes
      indicate that IOLs with an individual spherical aberration correction improve
      functional vision, especially contrast sensitivity, compared with standard
      aberration-free IOLs.

PMID- 30120006
TI  - Slow, slurred speech as an initial complaint in amyotrophic lateral sclerosis.
AB  - OBJECTIVE: Otorhinolaryngologic examinations at an early stage, particularly
      those conducted by vocal specialists, can make potentially important
      contributions to the diagnosis of bulbar-onset ALS patients. METHODS: We analyzed
      2623 patients (2010-2017) visited the ENT Voice Clinic, National Hospital
      Organization Tokyo Medical Center, with the primary complaint of speech or vocal
      dysfunction at the initial visit. Among those, 12 patients visited the voice
      clinic after consultations with other physicians but before receiving a diagnosis
      and we initially suspected bulbar-onset ALS due to slow, slurred speech (SSS). We
      analyzed the detail of those suspected ALS cases. RESULTS: Every patient
      suspected ALS patients consulted an average of 2.2 physicians before visiting the
      voice clinic and a total of 3.2 physicians before receiving the final diagnosis.
      The mean speech symptom duration before visiting the vocal clinic was 7.83 months
      in ALS, 24 months in MSA patients. The duration until final diagnosis after we
      referred them to neurologists was 2.16 months and 15.3 months, respectively.
      CONCLUSION: Otolaryngologists and primary care physicians to consider the
      possibility of ALS when patients present even with an only symptom of SSS. They
      should then refer such patients to neurologists for definitive diagnoses, leading
      to early detection and treatment of ALS.

PMID- 30120005
TI  - "Horizontal butterfly" technique in repair of radial meniscus tears: A
      biomechanical study.
AB  - INTRODUCTION: Radial meniscus tears are seen in young patients, especially with
      anterior cruciate ligament ruptures. Repair of complete radial meniscus tear is
      necessary for the meniscus functions. The most important factor for success of
      the meniscus repair is primary stability, but it is still unknown which technique
      is ideal repair technique. AIM: We developed a new suture technique named
      Horizontal Butterfly (HB). In this novel technique the contact between meniscal
      tissue and suture is more than Horizontal Loop (HL) that routinely used today.
      So, we think that this technique will provide better fixation than HL. We aimed
      to compare 2 repair techniques (HB vs. HL) using human lateral menisci
      biomechanically with cyclic loading and load to failure tests. MATERIAL-METHOD:
      We used 22 intact lateral meniscus obtained from patients that operated (total
      knee replacement) for varus gonarthrosis in our clinic. All menisci were cut
      radially. In the first group (n:11) menisci were repaired with standard
      horizontal loop technique, and in the second group (n:11) horizontal butterfly
      technique were used for repair. All specimens were tested with load to failure
      test after cyclic loading test (500 cycle X 5-30 N). RESULTS: Both groups have
      similar failure load (71,4 +/- 17,52 N vs. 77,9 +/- 28,49 N; p:0,559) and
      stiffness (24,46 +/- 19,19 N vs. 24,48 +/- 15,87 N; p:0,818). HB group has less
      peak displacement (6,26 +/- 1,24 mm vs. 8,4 +/- 1,92 mm; p:0,010). CONCLUSION:
      This novel repair technique decreases the amount of displacement according to
      standard technique while as strong as standard technique routinely used. In this
      way; we believe that it will increase the rate of healing in clinical use.

PMID- 30120007
TI  - Assessment of the needs for palliative care in advanced chronic patients on
      discharge.
AB  - OBJECTIVES: To describe the advanced chronic patients admitted to an internal
      medicine department and to identify whether they meet the criteria for the need
      for palliative care at the time of hospital discharge according to the NECPAL
      CCOMS.ICO(r) instrument. MATERIAL AND METHODS: Observational, descriptive and
      cross-sectional study performed on patients admitted to the internal medicine
      department of the Hospital Clinico Universitario Lozano Blesa (Saragossa), with a
      diagnosis of advanced progressive chronic diseases, from May 1, 2017 to September
      1, 2017 Variables: sex, age, advanced chronic disease, reason for admission,
      primary caregiver, origin (residence, address, etc.), number of readmissions in
      the previous year, existence of advance directives, disability of the patient,
      existence of order not to resuscitate, Charlson Index and all the variables
      contained in the NECPAL Instrument CCOMS-ICO (r) VERSION 3.0 2016. The data
      collection was done when the patient was scheduled to be discharged, having
      resolved the acute circumstance that led to the admission. RESULTS: the sample
      size was 142 patients who met the inclusion criteria: diagnosis of disease
      advanced evolutionary chronic ages, Charlson Index >=3 at the time the patient
      was scheduled to be discharged and signed their informed consent. The average age
      was 85.80 years and 50.7% were men. The average age of the women was higher than
      that of the men. The most prevalent advanced chronic disease was chronic heart
      disease. None of the patients had advance care directives in place.. Nutritional,
      functional, cognitive and severe dependence was determined in more than 50%. In
      more than 90% there was the presence of geriatric syndromes and persistent
      symptoms. The presence of emotional distress was also evident, as was the use of
      resources. CONCLUSIONS: A palliative approach in the care of chronicity would
      have a very positive impact on the quality of life of the patient and family,
      would positively influence health systems and would result in cost savings.
      Implementing the NECPAL CCOMS-ICO(r) instrument in the health services that serve
      high proportions of chronically ill patients, accompanied by training measures
      for health personnel and adaptation of resources, can introduce a qualitative and
      quantitative change that is very relevant in our the health system.

PMID- 30120008
TI  - A problem with different faces: Arbitrary levels of effect size.

PMID- 30120009
TI  - Perceived risk and decisional balance to HIV testing in men who have sex with men
      from Monterrey, Mexico.
AB  - : The perceived risk to HIV and the decisional balance (pros and cons) towards
      HIV testing are fundamental aspects for understanding the motivation of men who
      have sex with men to engage in behaviours that reduce or increase the risk of
      infection with the virus. OBJECTIVES: To describe the perceived risk of HIV and
      the decisional balance towards HIV testing and determine the association between
      perceived risk and the decisional balance towards HIV testing of men who have sex
      with men. METHOD: Descriptive correlational design, we used respondent-driven
      sampling, with which we recruited 202 men who have sex with men. RESULTS: Mean
      age of 27.79 (SD=8.13), 66.3% reported low perceived risk to HIV. The most
      significant pros were: "If I had HIV I would not want to infect anyone else"
      (95%) and "I would like to be sure I did not have HIV to tell my sexual partner"
      (90.6%). The most significant cons were: "I am afraid of the needle used for the
      HIV test" (53%), "people could reject me if they had HIV" (78.7%). Finally, there
      was a correlation between the perceived risk and the decisional balance towards
      HIV testing (rs=.759, p<.001). CONCLUSIONS: Given such data, in future
      interventions it is important to consider information about the importance of HIV
      testing on a regular basis, as well as actions to increase the perception of
      vulnerability to HIV in this population.

PMID- 30120010
TI  - Relationships between structural and psychological empowerment, mediated by
      person-centred processes and thriving for nursing home staff.
AB  - Person-centred care has been shown to have positive outcomes for patients and for
      staff. However, the complexity of the link between structural conditions, work in
      a person-centred manner and outcomes for staff is insufficiently described. We
      tested the relationship between structural empowerment and psychological
      empowerment, as mediated by nursing home staff members' self-ratings of working
      in a person-centred manner, the person-centred climate and thriving.
      Questionnaires were distributed to staff working in 12 nursing homes in Sweden. A
      serial mediation model was tested. The results showed that higher access to
      structural empowerment was related to higher psychological empowerment mediated
      by staff working in a more person-centred manner, improved person-centred
      climate, and improved staff ratings of thriving. These results point to the
      importance of strengthening the preconditions for staff to work in a person
      centred manner and nursing home managers play an important role in this.

PMID- 30120011
TI  - Spermatogonial stem cell potential of CXCR4-positive cells from prepubertal bull
      testes.
AB  - Spermatogonial stem cells (SSC) have the potential to restore spermatogenesis
      when transplanted into testes depleted of germ cells. Due to this property, SSC
      could be used in breeding programs and in transgenic animal research.
      Particularly in cattle, SSC are not as well characterized as in mice or humans.
      In mice, C-X-C Motif Chemokine Receptor 4 positive (CXCR4+) testicular cells have
      high SSC potential. It, therefore, was hypothesized that CXCR4 is a marker of
      undifferentiated spermatogonia in cattle. Using samples from pre-pubertal calves,
      the CXCR4 protein was detected by immunohistochemistry in a few cells of the
      seminiferous tubules. Testicular cells were isolated, frozen-thawed and submitted
      to magnetic-activated cell sorting using anti-CXCR4 antibody. Quantitative RT-PCR
      analysis revealed that CXCR4+ cells had THY1, OCT4 and ZBTB16 (or PLZF) mRNA in
      these cells. Flow cytometry results indicated that the proportion of THY1+ cells
      is enriched in CXCR4+ populations. Colonization potential of CXCR4+ cells was
      assessed after xenotransplantation into testes of nude mice treated with
      busulfan. Transplantation of CXCR4+ cells yielded an increase of 5.4-fold when
      compared to CXCR4- cells. These results indicate that CXCR4 could be used as a
      marker to enrich and sort cells of bulls with putative spermatogonial stem cell
      potential.

PMID- 30120012
TI  - Associations between serum calcium concentration and postpartum health and
      reproductive performance in dairy cows.
AB  - In the present study, the aim was to evaluate the associations between serum
      calcium concentration after calving and serum metabolites, postpartum disorders,
      and reproductive performance in dairy cows. Blood samples were collected from 200
      Holstein cows immediately and 1, 2, 4, 6, and 8 weeks after calving to measure
      serum metabolites and progesterone concentrations. Cows were divided into three
      groups on the basis of the mean serum calcium concentration after calving: a Low
      group (<7.9 mg/dL, n = 52), a Moderate group (7.9-9.6 mg/dL, n = 100), and a High
      group (>=9.7 mg/dL, n = 48). Total cholesterol (TCH) concentration was greater in
      the High group than in the Moderate group during the postpartum period (P < 
      0.01). The High group had greater albumin concentrations during the postpartum
      period (P <  0.01) and glucose concentrations after calving and 1 week postpartum
      (P <  0.05) than the Low and Moderate groups. The High group had a lesser
      incidence of retained placenta than the Low (P <  0.1) and Moderate (P <  0.01)
      groups, and a lesser incidence of clinical endometritis than the Moderate group
      (P <  0.05). The probability of resuming estrous cyclicity by 8 weeks postpartum
      was greater in the High group than in the Low group (hazard ratio = 3.71, P < 
      0.05). In conclusion, greater serum calcium concentration after calving is
      associated with greater serum TCH, albumin, and glucose concentrations, a lesser
      incidence of retained placenta, and clinical endometritis, and earlier resumption
      of estrous cyclicity in dairy cows.

PMID- 30120013
TI  - Management of Immune Checkpoint Inhibitor Toxicities: A Review and Clinical
      Guideline for Emergency Physicians.
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) are a novel class of drugs used
      in cancer immunotherapy that are becoming more commonly used among advanced-stage
      cancers. Unfortunately, these therapies are sometimes associated with often
      subtle, potentially fatal immune-related adverse events (irAEs). OBJECTIVES: We
      conducted a review of relevant primary research and clinical guidelines in
      oncology, pharmacology, and other literature, and synthesized this information to
      address the needs of the emergency physician in the acute management of irAEs.
      DISCUSSION: Although the antitumor effects of immunotherapies are desirable, the
      inhibition of immune checkpoints may also lead to loss of peripheral tolerance
      and a subsequent unleashing of the immune system on nontumor cells, leading to
      unintended tissue damage, which manifests as multisystem organ dysfunction. This
      tissue damage can affect nearly every organ system, with the dermatologic,
      gastrointestinal, endocrine, and pulmonary systems being the most commonly
      affected. Treatment may range drastically, depending on the severity of the irAE,
      starting with supportive care and moving toward high-dose steroids and additional
      immune modulators such as infliximab or intravenous immunoglobulin. CONCLUSION:
      With the increasing success and popularity of ICIs, emergency physicians will
      inevitably encounter increasing numbers of patients on these medications as well
      as the associated side effects. It is important that emergency physicians become
      aware of these irAEs and improve the detection of these processes to prevent
      inappropriate discharges, emergency department revisits, and downstream
      complications.

PMID- 30120014
TI  - Young Man After Overdose.

PMID- 30120015
TI  - Rapid Systematic Review: Age-Adjusted D-Dimer for Ruling Out Pulmonary Embolism.
AB  - BACKGROUND: Pulmonary embolism (PE) is a disease diagnosed relatively frequently
      in emergency departments (EDs). Evidence suggests that improved decision making
      may decrease inappropriate testing, unnecessary radiation exposure, and non
      beneficial treatment. Several studies have looked at the utility and safety of
      age-adjusting the D-dimer levels used to safely rule out PE. OBJECTIVE: This
      rapid systematic review sought to answer the question: Can an age-adjusted D
      dimer be used to safely rule out PE in patients over 50 years old? METHODS: We
      performed a structured review of PubMed from January 2012 to January 2018 limited
      to reports involving human subjects and written in the English language and
      containing relevant keywords. The highest-quality studies were then reviewed in a
      structured format. RESULTS: One hundred and eleven papers were identified for
      further review. Eight articles were determined to be appropriate for inclusion in
      this summary. These studies all used patient age (in years over 50) * 10 MUg/L
      (fibrinogen equivalent units) as their definition of an age-adjusted D-dimer.
      CONCLUSIONS: Age-adjusted D-dimer cutoff values, in combination with a non-high
      clinical probability, is safe and effective to essentially rule out PE in ED
      patients.

PMID- 30120016
TI  - Regulation of synaptic plasticity in hippocampal area CA2.
AB  - Synaptic plasticity in the hippocampus is thought to play a vital role in both
      the refinement of neuronal circuits during development and in learning in the
      mature brain. Synapses in hippocampal area CA1 are known for a robust capacity
      for long-term potentiation (LTP), whereas synapses in the stratum radiatum of
      hippocampal area CA2 are particularly resistant to such changes. Although we have
      yet to fully understand the mechanisms behind this resistance to plasticity, a
      number of genes and extracellular matrix components highly expressed in CA2
      appear to function as molecular brakes on plasticity and develop postnatally in
      the rodent brain. Curiously, the developmental profile of several CA2-enriched
      molecules is suggestive of a still undefined critical window of plasticity in the
      hippocampus.

PMID- 30120017
TI  - Pulmonary Lymphangitic Carcinomatosis From Renal Cell Carcinoma.
AB  - Lymphangitic carcinomatosis, the presence of tumor within the pulmonary
      lymphatics, occurs in the setting of malignant tumors and is associated with a
      poor prognosis. Here we describe a case of lymphangitic carcinomatosis in the
      setting of renal cell carcinoma and review the radiological manifestations of
      this disease.

PMID- 30120018
TI  - Memory, Mood, and Marriage: Examining the Interplay in Older Adults.

PMID- 30120020
TI  - Linear localized morphea associated with golimumab in a patient with
      spondyloarthritis.

PMID- 30120021
TI  - Antisynthetase Syndrome Complicating the Course of Established Case with
      Rheumatoid Arthritis: A Rare and Under-recognized Overlapping Disease.
AB  - A 52-year-old male patient developed RA in March 2009 at the age of 43, with
      symmetric polyarthritis and active synovitis affecting hands, knees, ankles and
      both feet without symptoms or signs suggestive of extra-articular features.
      Laboratory investigations showed negative RF and positive anti-CCP antibodies,
      negative ANA, negative anti-dsDNA antibodies; the X-rays of both hands showed
      typical erosive changes in RA and fulfilled the new ACR/EULAR (2010) criteria of
      RA. The patient achieved remission on a combination of DMARDs. He did well until
      January 2017 when he developed acute onset of progressive chest pain, dyspnea,
      and acute respiratory failure. High-resolution CT of the lung showed extensive
      areas of ground glass veiling, and interstitial subpleural infiltrates were found
      consistent with aggressive interstitial lung disease (ILD). Autoantibodies
      against extractable nuclear antigens were screened and showed positive results
      for anti-RO and anti-Jo1 autoantibodies. The positive anti-Jo1was an expression
      of anti-synthetase syndrome complicating the RA course and explained the rapidly
      aggressive course of ILD.

PMID- 30120019
TI  - Longitudinal Associations Between Cognitive Functioning and Depressive Symptoms
      Among Older Adult Spouses in the Cardiovascular Health Study.
AB  - OBJECTIVE: To examine the bidirectional associations between older adult spouses'
      cognitive functioning and depressive symptoms over time. DESIGN: Longitudinal,
      dyadic path analysis with the actor-partner interdependence model. SETTING: Data
      were from visit 5 (1992/1993), visit 8 (1995/1996), and visit 11 (1998/1999) of
      the Cardiovascular Health Study, a multisite, longitudinal, observational study
      of risk factors for cardiovascular disease in adults 65 years or older.
      Demographic information was from the 1989/1990 original and 1992/1993 African
      American cohort baseline visits. PARTICIPANTS: Husbands and wives from 1,028
      community-dwelling married couples (N = 2,065). MEASUREMENTS: Cognitive
      functioning was measured with the Modified Mini-Mental State Exam. Depressive
      symptoms were measured using the 10-item Center for Epidemiologic Studies
      Depression Scale. Age, education, and disability (activities of daily living and
      instrumental activities of daily living) were included as covariates. RESULTS:
      Cross-partner associations (partner effects) revealed that one spouse's greater
      depressive symptoms predicted the other spouse's lower cognitive functioning, but
      a spouse's lower cognitive functioning did not predict the other spouse's greater
      depressive symptoms over time. Within-individual associations (actor effects)
      revealed that an individual's lower cognitive functioning predicted the
      individual's greater depressive symptoms over time, but greater depressive
      symptoms did not predict lower cognitive functioning over time. Effects did not
      differ for husbands and wives. CONCLUSION: Having a spouse who is depressed may
      increase one's risk of cognitive decline as well as one's risk of depression.
      Interventions for preventing cognitive decline and depression among older adults
      may be enhanced by considering the marital context.

PMID- 30120022
TI  - Exploring putative genetic determinants of inter-individual phenotypic
      heterogeneity in sickle cell disease: A cross-sectional Jamaican cohort-based
      study.
AB  - Patients with sickle cell disease (SCD) display puzzling inter-individual
      phenotypic heterogeneity, conceivably related to inherent differences in
      antioxidant protection, hemoglobin binding, bilirubin catabolism and methyl group
      handling. Therefore, we explored putative associations between clinically
      important phenotypic measures and functional polymorphisms within specific
      candidate genes encoding glutathione S-transferase, haptoglobin, uridine 5'
      diphospho-glucuronosyltransferase 1A1, methyl tetrahydrofolate reductase, 5
      methyltetrahydrofolate-homocysteine methyltransferase, and cystathionine beta
      synthase. Two-hundred and thirty SCD participants (mean age 25.1 +/- 2.8) were
      recruited from Jamaica's Annual Sickle Cell Unit Cohort Review - two-hundred and
      five had homozygous hemoglobin SS (HbSS) disease, twenty-five had hemoglobin SC
      (HbSC) disease. Regression analyses revealed some novel genotype-phenotype
      associations. HbSC participants had significantly lower mean lactate
      dehydrogenase (p = 0.01) and glutathione (p < 0.001) values than HbSS
      participants. Glutathione S-transferase P1 (GSTP1) was significantly associated
      with mean corpuscular hemoglobin concentration using univariate (p = 0.044) and
      multivariable regression (p = 0.012). 5-methyltetrahydrofolate-homocysteine
      methyltransferase (MTR) was significantly associated with hemoglobin F % using
      univariate (p = 0.010) and multivariable regression (p = 0.009). In conclusion,
      this exploratory cross-sectional study generated novel, useable, and informative
      genotype-phenotype estimates of association, but larger studies are needed to
      determine whether these specific variants are related to inter-individual
      phenotypic variability in SCD.

PMID- 30120024
TI  - Predictors of renal complications in pediatric patients with type 1 diabetes
      mellitus: A prospective cohort study.
AB  - AIMS: Diabetic Nephropathy (DN) is rarely encountered in childhood, otherwise
      early subclinical abnormalities are detectable few years after diabetes
      diagnosis. Our aim was to evaluate the incidence rate of microalbuminuria in
      childhood onset type 1 diabetes (DM1) patients. Secondary aim was to examine
      which variables could influence the development of DN. METHODS: We longitudinally
      evaluated 137 young patients with DM1 from diagnosis (1994-2004) for a median of
      11.8 years (1st-3rd q: 9.7-15.0). Overnight albumin excretion rate, degree of
      metabolic control, presence of microangiopathic complications and autoimmune co
      morbidities were retrospectively collected. RESULTS: DN was observed in 16/137
      cases (11.7%), with an incidence rate of 10.0 per 1000 person-years. Young T1D
      patients with persistent micro/macro-albuminuria were more likely to have higher
      HbA1c concentrations over the last four years (P = 0.04), and were more likely to
      have retinopathy (P = 0.011) and subclinical peripheral neuropathy (P = 0.003).
      CONCLUSIONS: DN predictors were age at DM1 diagnosis and mean HbA1c levels. Even
      if DN incidence is lower than reported, periodical screening is mandatory.
      Moreover, borderline microalbuminuria as additional risk factor deserves
      attention.

PMID- 30120025
TI  - Measurement of Trabecular Bone Score of the Spine by Low-Dose Imaging System
      (EOS(r)): A Feasibility Study.
AB  - : Purpose/Introduction: Measurement of trabecular bone score (TBS(r)) of the
      lumbar spine on dual energy X-ray absorptiometry (DXA) devices improves fracture
      risk prediction. We conducted a proof of concept study to assess the feasibility
      of TBS(r) measured on the low-dose imaging system EOS(r). METHODS: TBS was
      assessed on both DXA and EOS(r) in 122 patients aged >= 50 yr, receiving no anti
      osteoporotic treatment. The TBS(r) was computed on full-body EOS(r) images,
      focusing on the lumbar spine region. The patients were also scanned with a DXA
      bone densitometer (Hologic) and the spine and hip bone mineral density (g/cm2)
      were computed. RESULTS: TBS(r) measurement on EOS(r) was not possible in 34
      patients due to technical problems. It could be measured on both DXA and EOS(r)
      in 88 patients (28 with severe low-trauma fracture and 60 without fracture). TBS
      EOS values were significantly lower in fractured patients compared to
      nonfractured patients. TBS-EOS was associated with the presence of fractures as
      reported by an AUC of 0.70. Odds ratio of TBS-EOS for the presence of severe low
      trauma fracture was 2.00 [1.24-3.25], p = 0.005. CONCLUSIONS: This proof of
      concept study, based on a prototype version of the TBS-EOS, demonstrated the
      feasibility of the measurement of TBS(r) on low-dose EOS(r) imaging devices.
      Results show that the TBS-EOS was lower in patients with severe low-trauma
      fractures compared to nonfractured patients independently from bone mineral
      density. Some technical issues need to be solved before its eventual use in
      routine clinical settings. Additional prospective studies are still needed to
      define the actual contribution of this new technique.

PMID- 30120027
TI  - Concurrent Assessment of Cartilage Morphology and Bone Microarchitecture in the
      Human Knee Using Contrast-Enhanced HR-pQCT Imaging.
AB  - Osteoarthritis (OA) is a prevalent articular disease characterized by whole joint
      degradation, including articular cartilage and bone. Presently, no single imaging
      modality is well suited to concurrently capture these changes. Recent ex vivo
      animal studies have demonstrated the efficacy of utilizing contrast agents in
      conjunction with micro-CT as a means of evaluating cartilage and bone alterations
      concurrently, though no work as of yet has been performed in large animal models
      or humans. This study sought to develop and validate a novel joint imaging
      technique, contrast enhanced high resolution peripheral quantitative computed
      tomography (CEHR-pQCT), to concurrently assess bone microarchitecture and
      cartilage morphology in the whole human knee. Fresh frozen cadaveric knees were
      harvested (n = 10) and scanned using magnetic resonance imaging (MRI), HR-pQCT
      without contrast, and HR- pQCT following intra-articular injection of nonionic
      contrast media. Cartilage morphology and bone microarchitecture were evaluated in
      weight bearing regions of interest in both the tibia and femur. Joints were then
      disarticulated, and the articular cartilage thickness measured by needle probe.
      Measures of cartilage morphology, thickness and volume, were found to be
      significantly less when measured by CEHR- pQCT compared to magnetic resonance
      imaging in all regions. Compared to needle probing, cartilage thickness measured
      by CEHR-pQCT was less in the lateral tibia and greater in the medial tibia. Bone
      microarchitecture was found to be significantly different when measured with CEHR
      pQCT compared to HR-pQCT, where cortical bone mineral density (BMD) was
      depressed, and trabecular bone mineral density was greater. This study
      demonstrates that CEHR-pQCT can be used to concurrently measure cartilage
      morphology and bone microarchitecture; however, systematic errors impact both
      measures. This is the first study using contrast media in combination with HR
      pQCT in whole joints. Additionally, all imaging parameters, as well as the
      contrast media, were selected to be directly transferable to in vivo studies,
      laying the foundation to perform in vivo scanning of knee cartilage and bone.

PMID- 30120028
TI  - What I have learned about being successful as an orthopedic surgeon.

PMID- 30120026
TI  - Bone Mineral Density Around the Knee Joint: Correlation With Central Bone Mineral
      Density and Associated Factors.
AB  - INTRODUCTION: The aims of this study were to (1) assess the bone mineral density
      (BMD) around the knee joint, (2) determine the correlation between central and
      knee BMDs, and (3) investigate the factors associated with BMD around the knee
      joint in patients with knee osteoarthritis (OA). METHODOLOGY: This cross
      sectional study included 122 patients who underwent total knee arthroplasty.
      Central and knee dual-energy X-ray absorptiometry was performed preoperatively.
      BMD at 6 regions of interest (ROIs) around the knee joint were measured, and
      their correlations with central BMD were determined using Spearman's correlation
      analysis. Lower limb alignment, severity of OA, body mass index (BMI),
      preoperative functional and pain scores were assessed to elucidate the factors
      associated with knee BMD using linear regression analysis. RESULTS: Around the
      knee joint, BMD was the lowest at the distal femoral metaphysis and lateral
      tibial condyle. Knee BMD was significantly correlated with central BMD. However,
      the correlation coefficients varied by the ROI. Additionally, multivariate
      analysis revealed different associations with respect to the regions around the
      knee joint. Varus alignment of the lower limb was associated with increased BMD
      of the medial condyles and decreased BMD of lateral condyles. High grade OA was a
      protective factor; it was associated with increased BMD at the lateral condyles
      of the femur and tibia. Higher BMI was an independent protective factor in all
      ROIs around the knee joint except the lateral femoral condyles. Lower functional
      level was not associated with decreased BMD, whereas a higher pain score was
      significantly associated with lower BMD at the proximal tibial metaphysis.
      CONCLUSIONS: Knee BMD was significantly correlated with central BMD. However, the
      correlations varied with the regions around the knee joint probably due to their
      independent association with the alignment of the lower limb, severity of OA,
      BMI, and preoperative pain level.

PMID- 30120023
TI  - Epitranscriptomic Code and Its Alterations in Human Disease.
AB  - Innovations in epitranscriptomics have resulted in the identification of more
      than 160 RNA modifications to date. These developments, together with the recent
      discovery of writers, readers, and erasers of modifications occurring across a
      wide range of RNAs and tissue types, have led to a surge in integrative
      approaches for transcriptome-wide mapping of modifications and protein-RNA
      interaction profiles of epitranscriptome players. RNA modification maps and
      crosstalk between them have begun to elucidate the role of modifications as
      signaling switches, entertaining the notion of an epitranscriptomic code as a
      driver of the post-transcriptional fate of RNA. Emerging single-molecule
      sequencing technologies and development of antibodies specific to various RNA
      modifications could enable charting of transcript-specific epitranscriptomic
      marks across cell types and their alterations in disease.

PMID- 30120029
TI  - Arthroscopic autologous chondrocyte implantation in the glenohumeral joint: a
      case report.

PMID- 30120030
TI  - Hand or spoon? Exploring the neural basis of affective touch in 5-month-old
      infants.
AB  - In adults, affective touch leads to widespread activation of cortical areas
      including posterior Superior Temporal Sulcus (pSTS) and Inferior Frontal Gyrus
      (IFG). Using functional Near Infrared Spectroscopy (fNIRS), we asked whether
      similar areas are activated in 5-month-old infants, by comparing affective to non
      affective touch. We contrasted a human touch stroke to strokes performed with a
      cold metallic spoon. The hypothesis that adult-like activation of cortical areas
      would be seen only in response to the human touch stroke was not confirmed.
      Similar patterns of activation were seen in both conditions. We conclude that
      either the posterior STS and IFG have not yet developed selective responses to
      affective touch, or that additional social cues are needed to be able to identify
      this type of touch.

PMID- 30120031
TI  - A 'cold case' of care: Looking at old data from a new perspective in mummy
      research.
AB  - In 1973, analysis of the mummified remains of a young boy dated to 700AD and from
      the Late Nasca period (Peru) identified (i) chronic Pott's disease, leading to
      loss of lower body mobility, and (ii) acute miliary tuberculosis, affecting most
      organs and the immediate cause of death (Allison et al., 1973). This report was
      the first to establish, beyond dispute, the presence of tuberculosis in the
      Americas before the arrival of Europeans. Here, we revisit the 'Nasca Boy' from a
      bioarchaeology of care perspective. Contextualising the original study's results
      within what is known of contemporary lifeways, we apply the bioarchaeology of
      care methodology in considering the Nasca Boy's experience of living with
      tuberculosis; the type of care he required and how this may have evolved over a
      period of deteriorating health; and what such caregiving may suggest both about
      social organisation within his community and some of the more everyday aspects of
      Nasca existence. Up to now, the bioarchaeology of care approach has been employed
      almost exclusively with skeletal evidence; in this analysis of the Nasca Boy's
      remains, and in the accompanying wider-ranging discussion, we illustrate the
      potential of preserved soft tissue evidence to contribute to research into
      disability and care in the past. Although this report functions as a stand-alone
      case study, to obtain maximum benefit it should be read in conjunction with the
      Introduction to the special International Journal of Paleopathology issue on
      'mummy studies and the bioarchaeology of care' (Nystrom and Tilley, 2018).

PMID- 30120032
TI  - [Specimen labelling: A complex process with a high error rate].
AB  - : Errors associated with the labelling of laboratory specimens repeatedly occur
      in health facilities and are often described in Critical Incident Reporting
      Systems (CIRS). The analysis of these error reports and the complexity of the
      specimen collection process pose major challenges for responsible health care
      professionals. To examine which errors occur in the labelling of laboratory
      specimens, and what leads to their detection, the error reports of 42 Swiss
      hospitals within the Critical Incident Reporting & Reaching NETwork (CIRRNET)
      were systematically analysed. METHOD: Within the scope of a reporting month in
      the year 2016, 42 hospitals were asked to pay particular attention to the issue
      of mislabelled laboratory specimens, to report these errors in the local CIRS
      system, and to forward the information to the CIRRNET database. In addition,
      using a systematic keyword search, a search for old error reports on the
      mislabelling of laboratory specimens was conducted in the CIRRNET database and
      the results extracted. 227 error reports were finally included in the analysis.
      All these error reports were analysed systematically and by content, and the
      problem areas described in these reports allocated to newly defined categories.
      The systematic analysis included: the time of error detection, the problem area
      described, the length of time between error occurrence and error detection, as
      well as possible safety barriers. RESULTS: The majority (52 %) of labelling
      errors of laboratory specimens are detected in the laboratory, 21.1 % on the
      hospital ward before the specimens are sent to the laboratory to be processed,
      and a further 24.7 % at a very late stage when test results are associated with
      the patient on the ward. The analysis of the problem areas described showed that
      patient identification (7.9 %) was a key issue. The most frequent errors occurred
      in connection with the labelling of laboratory test tubes (45.4 %) and analysis
      forms or requisition slips (33 %). Numerous errors went undetected throughout the
      entire process, i.e. right up until the moment when the test result was finally
      assigned to the patient. The analysis also provided information about possible
      safety barriers for future prevention of laboratory specimen mislabelling.
      CONCLUSIONS: A content-analysis approach is essential to the evaluation of error
      reports as it is the only way to identify all the problems of laboratory specimen
      mislabelling described. Furthermore, a deductive approach also facilitates the
      identification of possible safety barriers. The findings provide valuable
      information for mislabelling prevention approaches that is not otherwise
      available. Further analysis of error reports from Critical Incident Reporting
      Systems is necessary in order to gain more experience with the methodical
      approach and to draw conclusions as to whether the complex process of analysing
      each individual error report yields information that is more useful than the
      analysis of the error reports of an identified problem area.

PMID- 30120033
TI  - Mirror Illusion for Sensori-Motor Training in Stroke: A Randomized Controlled
      Trial.
AB  - BACKGROUND: Poststroke, sensory deficits are not uncommon. In spite of the close
      association between the sensory and motor recovery, the deficits are usually
      underemphasized. Mirror therapy (MT), a neural-based approach for the motor
      deficit has not been explored for the sensory impairment. The objective of the
      present study was to develop and determine the effect of a MT program for sensori
      motor impairment among poststroke subjects. METHODS DESIGN: Randomized controlled
      trial. SETTING: Functional therapy laboratory of Rehabilitation Institute.
      PARTICIPANTS: Thirty-one chronic poststroke subjects (17 experimental and 14
      controls), aged between 30 and 60years, with <= diminished light touch in the
      hand. OUTCOME MEASURE: Semmes Weinstein Monofilament (cutaneous threshold), 2
      Point discrimination test (touch discrimination) and Fugl-Meyer Assessment (hand
      motor recovery). INTERVENTION: The experimental group received sensory stimulus
      such as tactile perception and motor tasks on the less-affected hand using mirror
      box. The control counterparts underwent only dose-matched conventional program.
      30 sessions with a frequency of 5/week were imparted to the groups. RESULTS: Post
      intervention, there was a significant (P < .004) increase up to 30% positive
      touch-response for the hand quadrants among the experimental group in comparison
      to only 13.5% rise for the same among the controls. The cutaneous threshold of
      the less-affected palm also improved significantly among the experimental
      subjects in comparison to the controls (P = .04). CONCLUSION: MT may be
      considered as a promising regime for enhancing cutaneous sensibility in stroke.
      The mirror illusion induced by MT may be utilized for sensory and motor deficits
      as well as for the more-affected and less-affected hands.

PMID- 30120034
TI  - The Effects of Mouse Recombinant Resistin on mRNA Expression of Proinflammatory
      and Anti-Inflammatory Cytokines and Heat Shock Protein-70 in Experimental Stroke
      Model.
AB  - BACKGROUND: Our recent research showed that resistin has a neuroprotective effect
      against stroke-induced injury through suppressing apoptosis and oxidative stress.
      However, the molecular mechanism of neuroprotection of resistin is unclear. This
      work was designed to examine the effect of mouse recombinant resistin on mRNA
      expression of Tumor necrosis factor-alpha (TNF-alpha), Interleukin-1beta (IL
      1beta), Interleukin-10 (IL-10), Transforming growth factor-beta1 (TGF- beta1),
      and Heat shock protein-70 (HSP-70) in mouse model of stroke. MATERIALS AND
      METHODS: Transient focal cerebral ischemia was induced by the middle cerebral
      artery occlusion (MCAO) in mice. TNF-alpha, IL-1beta, IL-10, TGF-beta1, and HSP
      70 mRNA were detected at sham (0 hour), 3 hours, 6 hours, 12 hours, and 24 hours
      after MCAO using real-time QRT-PCR method. Moreover, animals were treated with
      resistin at the dose of 400ng/mouse at the commencement of MCAO, and mRNA
      expression of the cytokines and HSP-70 was measured 24 hours after MCAO. RESULTS:
      Tumor necrosis factor-alpha and IL-1beta mRNA expression markedly increased at 12
      hour time point and then returned to the basal level at 24 hours after MCAO; but
      HSP-70 mRNA expression increased at 24-hour time point. Furthermore, resistin
      (400 ng/mouse) significantly increased TGF-beta1 and IL-10 and decreased HSP-70
      gene expression at 24 hours after MCAO. CONCLUSIONS: Our findings revealed that a
      molecular mechanism of attenuating ischemic damage by resistin administration
      probably is increased mRNA expression of anti-inflammatory cytokines. However,
      applying resistin in the clinical settings for the treatment of stroke deserves
      further researches in the future.

PMID- 30120035
TI  - Electrocadiographic Scoring Helps Predict Left Ventricular Wall Motion
      Abnormality Commonly Observed after Subarachnoid Hemorrhage.
AB  - BACKGROUND: Cardiac wall motion abnormality (WMA) is a common complication in
      patients with subarachnoid hemorrhage (SAH) and is one determinant of their
      prognosis. The aim of this study was to examine whether the electrocardiography
      (ECG) findings at admission could predict WMA commonly observed after SAH.
      MATERIALS AND METHODS: We studied 161 SAH patients with SAH who were hospitalized
      in our institution between April 2007 and November 2010. We performed bedside 2
      dimensional transthoracic echocardiography and 12-lead surface ECG within 24hours
      of SAH onset. Each of the following ECG changes was scored as having 1 point: ST
      elevation, ST depression and T wave inversion. We summed up the points in every
      patient and compared with WMA evaluated by echocardiography. RESULTS: The study
      subjects were classified into 2 groups based on the presence of WMA. Multivariate
      analysis revealed that ST elevation, ST depression and T wave inversion were
      strong independent predictors of WMA. Receiver operating characteristic curve
      determined that the threshold value to predict WMA was 4 points (sensitivity
      86.5%, specificity 83.1%, AUC 0.94, P < .0001). CONCLUSIONS: In conclusion, a
      novel ECG score may well predict WMA after SAH which may associate with an
      increased risk of mortality.

PMID- 30120036
TI  - Chemical Sympathectomy, but not Adrenergic Blockade, Improves Stroke Outcome.
AB  - BACKGROUND: A robust adrenergic response following stroke impairs lymphocyte
      function, which may prevent the development of autoimmune responses to brain
      antigens. We tested whether inhibition of the sympathetic response after stroke
      would increase the propensity for developing autoimmune responses to brain
      antigens. METHODS: Male Lewis rats were treated with 6-hydroxydopamine (OHDA)
      prior to middle cerebral artery occlusion (MCAO), labetalol after MCAO, or
      appropriate controls. Behavior was assessed weekly and animals survived to 1
      month at which time ELISPOT assays were done on lymphocytes from spleen and brain
      to determine the Th1 and Th17 responses to myelin basic protein (MBP), ovalbumin
      (OVA), and concanavalin A. A subset of animals was sacrificed 72 hours after MCAO
      for evaluation of infarct volume and lymphocyte responsiveness. Plasma C-reactive
      protein (CRP) was measured as a biomarker of systemic inflammation. RESULTS:
      Despite similar initial stroke severity and infarct volumes, 6-OHDA-treated
      animals lost less weight and experienced less hyperthermia after stroke. 6-OHDA
      treated animals also had decreased CRP in circulation early after stroke and
      experienced better neurological outcomes at 1 month. The Th1 and Th17 responses
      to MBP did not differ among treatment groups at 1 month, but the Th1 response to
      OVA in spleen was more robust in labetalol and less robust in 6-OHDA-treated
      animals. CONCLUSIONS: Chemical sympathectomy with 6-OHDA, but not treatment with
      labetalol, decreased systemic markers of inflammation early after stroke and
      improved long-term outcome. An increase in Th1 and Th17 responses to MBP was not
      seen with inhibition of the sympathetic response.

PMID- 30120037
TI  - Clinicopathologic factors related to surgical margin involvement, reoperation,
      and residual cancer in primary operable breast cancer - An analysis of 2050
      patients.
AB  - BACKGROUND: To evaluate whether clinicopathologic factors are related to surgical
      margin involvement, reoperation, and residual cancer in primary operable breast
      cancer. METHODS: Identification of patients at increased risk for positive
      surgical margins may enhance clinical preoperative decision-making and lower the
      reoperation rate. In this retrospective study, we analyzed the factors associated
      with positive surgical margins, the need for re-excision, and residual cancer
      detection in re-excised specimens in a cohort of 2050 women who underwent either
      breast-conserving surgery (BCS) or mastectomy for primary operable breast cancer.
      RESULTS: Positive surgical margins were detected in 151 (7.4%) of the 2050
      patients. The incidence of positive surgical margins was 11.3% (118/1042) in the
      BCS group and 3.3% (33/1008) in the mastectomy group (P < 0.001). In multivariate
      analysis, lower body mass index (BMI), larger tumor size, and pathologic evidence
      of multifocal disease were associated with positive surgical margin involvement
      in the BCS group. Younger age and ductal carcinoma in situ (DCIS) histologic
      subtypes (Odds ratio (OR) = 2.165, 95% CI = 1.253-4.323) were associated with
      higher risk of re-operations. Preoperative MRI examination was associated with
      decreased risk for margin involvement in the BCS group (OR = 0.530, 95% CI =
      0.332-0.842) and reoperation (OR = 0.302, 95% CI = 0.119-0.728). DCIS histologic
      subtypes were associated with higher residual tumor incidence than other types of
      breast cancer. CONCLUSIONS: Lower BMI, larger tumor size, pathologic evidence of
      multifocal disease, and no preoperative MRI evaluation were associated with
      increased risk for positive surgical margin involvement. DCIS with positive
      surgical margins was associated with increased risk for reoperation and residual
      cancer detection at re-excision.

PMID- 30120038
TI  - 68Ga-PSMA PET/CT Replacing Bone Scan in the Initial Staging of Skeletal
      Metastasis in Prostate Cancer: A Fait Accompli?
AB  - PURPOSE: 68Ga ligands targeting prostate-specific membrane antigen (PSMA) are
      rapidly emerging as a significant step forward in the management of prostate
      cancer. PSMA is a type II transmembrane protein with high expression in prostate
      carcinoma cells. We prospectively evaluated the use of 68Ga-PSMA positron
      emission tomography/computed tomography (PET/CT) in patients with prostate cancer
      and compared the results to those for technetium-99m (99mTc)-10
      metacyloyloxydecyl dihydrogen phosphate (MDP) bone scintigraphy (BS). PATIENTS
      AND METHODS: A total 113 patients with biopsy-proven prostate cancer referred for
      standard-of-care BS were prospectively enrolled onto this study. 68Ga-PSMA PET/CT
      was performed after BS. Metastasis diagnosed on each technique was compared
      against a final diagnosis based on CT, magnetic resonance imaging, skeletal
      survey, clinical follow-up, and histologic correlation. RESULTS: Ninety-one bone
      lesions were interpreted as bone metastases in 25 men undergoing 68Ga-PSMA PET/CT
      compared to only 61 lesions in 19 men undergoing 99mTc-MDP BS. Of the 7 bone
      scans that missed skeletal metastases, 54% of these missed lesions were due to
      either marrow or lytic skeletal metastases. The median standardized uptake value
      in all malignant bone lesions was 13.84. 68Ga-PSMA PET/CT showed significantly
      higher sensitivity and accuracy than BS (96.2% vs. 73.1%, and 99.1% vs. 84.1%)
      for the detection of skeletal lesions. For extraskeletal lesions, 68Ga-PSMA
      PET/CT showed an additional 96 unexpected lesions with a median standardized
      uptake value of 17.6. CONCLUSION: 68Ga-PSMA PET/CT is superior to and can
      potentially replace bone scan in the evaluation for skeletal metastases in the
      clinical and trial setting because of its ability to detect lytic and bone marrow
      metastases.

PMID- 30120040
TI  - Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older
      adults.
AB  - INTRODUCTION: Blood-brain barrier (BBB) breakdown is observed in older versus
      younger adults and in late-onset Alzheimer's disease versus age-matched controls,
      but its causes and consequences in aging are unclear. We tested the hypothesis
      that BBB breakdown is associated with cognitive decline and inflammation in
      nondemented elders. METHODS: Cerebrospinal fluid and serum inflammatory markers
      were measured using sandwich immunoassays in 120 subjects. Least Absolute
      Shrinkage and Selection Operator-logistic regression selected cerebrospinal fluid
      and serum signatures that best classified BBB impairment defined by the
      cerebrospinal fluid albumin index >=9. Linear regression examined changes in
      Clinical Dementia Rating sum of boxes as a function of BBB integrity at baseline.
      RESULTS: Mean age was 70 years, mean Mini-Mental State Examination was 27, and
      BBB impairment was recorded in 13.5%. BBB breakdown was associated with cognitive
      decline (P = .015). Cerebrospinal fluid intercellular adhesion molecule-1,
      vascular endothelial growth factor, interleukin-8, serum amyloid A, macrophage
      derived chemokine, and gender generated an area under the curve of 0.95 for BBB
      impairment, and serum IL-16, VEGF-D, IL-15, and other variables generated an AUC
      of 0.92 for BBB impairment. Serum interleukin-16, vascular endothelial growth
      factor-D, interleukin-15, and other variables generated an area under the curve
      of 0.92. DISCUSSION: BBB breakdown is associated with more rapid cognitive
      decline. Inflammatory mechanisms, including cell adhesion, neutrophil migration,
      lipid metabolism, and angiogenesis may be implicated. Cell adhesion, neutrophil
      migration, high-density lipoprotein metabolism, and angiogenesis are implicated.

PMID- 30120042
TI  - Can radiomics personalise immunotherapy?

PMID- 30120041
TI  - A radiomics approach to assess tumour-infiltrating CD8 cells and response to anti
      PD-1 or anti-PD-L1 immunotherapy: an imaging biomarker, retrospective multicohort
      study.
AB  - BACKGROUND: Because responses of patients with cancer to immunotherapy can vary
      in success, innovative predictors of response to treatment are urgently needed to
      improve treatment outcomes. We aimed to develop and independently validate a
      radiomics-based biomarker of tumour-infiltrating CD8 cells in patients included
      in phase 1 trials of anti-programmed cell death protein (PD)-1 or anti-programmed
      cell death ligand 1 (PD-L1) monotherapy. We also aimed to evaluate the
      association between the biomarker, and tumour immune phenotype and clinical
      outcomes of these patients. METHODS: In this retrospective multicohort study, we
      used four independent cohorts of patients with advanced solid tumours to develop
      and validate a radiomic signature predictive of immunotherapy response by
      combining contrast-enhanced CT images and RNA-seq genomic data from tumour
      biopsies to assess CD8 cell tumour infiltration. To develop the radiomic
      signature of CD8 cells, we used the CT images and RNA sequencing data of 135
      patients with advanced solid malignant tumours who had been enrolled into the
      MOSCATO trial between May 1, 2012, and March 31, 2016, in France (training set).
      The genomic data, which are based on the CD8B gene, were used to estimate the
      abundance of CD8 cells in the samples and data were then aligned with the images
      to generate the radiomic signatures. The concordance of the radiomic signature
      (primary endpoint) was validated in a Cancer Genome Atlas [TGCA] database dataset
      including 119 patients who had available baseline preoperative imaging data and
      corresponding transcriptomic data on June 30, 2017. From 84 input variables used
      for the machine-learning method (78 radiomic features, five location variables,
      and one technical variable), a radiomics-based predictor of the CD8 cell
      expression signature was built by use of machine learning (elastic-net
      regularised regression method). Two other independent cohorts of patients with
      advanced solid tumours were used to evaluate this predictor. The immune phenotype
      internal cohort (n=100), were randomly selected from the Gustave Roussy Cancer
      Campus database of patient medical records based on previously described, extreme
      tumour-immune phenotypes: immune-inflamed (with dense CD8 cell infiltration) or
      immune-desert (with low CD8 cell infiltration), irrespective of treatment
      delivered; these data were used to analyse the correlation of the immune
      phenotype with this biomarker. Finally, the immunotherapy-treated dataset (n=137)
      of patients recruited from Dec 1, 2011, to Jan 31, 2014, at the Gustave Roussy
      Cancer Campus, who had been treated with anti-PD-1 and anti-PD-L1 monotherapy in
      phase 1 trials, was used to assess the predictive value of this biomarker in
      terms of clinical outcome. FINDINGS: We developed a radiomic signature for CD8
      cells that included eight variables, which was validated with the gene expression
      signature of CD8 cells in the TCGA dataset (area under the curve [AUC]=0.67; 95%
      CI 0.57-0.77; p=0.0019). In the cohort with assumed immune phenotypes, the
      signature was also able to discriminate inflamed tumours from immune-desert
      tumours (0.76; 0.66-0.86; p<0.0001). In patients treated with anti-PD-1 and PD
      L1, a high baseline radiomic score (relative to the median) was associated with a
      higher proportion of patients who achieved an objective response at 3 months (vs
      those with progressive disease or stable disease; p=0.049) and a higher
      proportion of patients who had an objective response (vs those with progressive
      disease or stable disease; p=0.025) or stable disease (vs those with progressive
      disease; p=0.013) at 6 months. A high baseline radiomic score was also associated
      with improved overall survival in univariate (median overall survival 24.3 months
      in the high radiomic score group, 95% CI 18.63-42.1; vs 11.5 months in the low
      radiomic score group, 7.98-15.6; hazard ratio 0.58, 95% CI 0.39-0.87; p=0.0081)
      and multivariate analyses (0.52, 0.35-0.79; p=0.0022). INTERPRETATION: The
      radiomic signature of CD8 cells was validated in three independent cohorts. This
      imaging predictor provided a promising way to predict the immune phenotype of
      tumours and to infer clinical outcomes for patients with cancer who had been
      treated with anti-PD-1 and PD-L1. Our imaging biomarker could be useful in
      estimating CD8 cell count and predicting clinical outcomes of patients treated
      with immunotherapy, when validated by further prospective randomised trials.
      FUNDING: Fondation pour la Recherche Medicale, and SIRIC-SOCRATE 2.0, French
      Society of Radiation Oncology.

PMID- 30120044
TI  - Mentoring Major Career Decisions: The Agony and Sadness of Choice.

PMID- 30120045
TI  - Creating a Culture to Support Radiology Resident Mothers.

PMID- 30120043
TI  - Key Ingredients of a Breast Imaging Fellowship-A Recipe for Success.
AB  - OBJECTIVE: In 2013, the ACR and Society of Breast Imaging created a curriculum to
      standardize the knowledge of graduates from breast imaging fellowships. Despite
      this, however, there remains a need to provide guidance to programs as to how to
      structure and organize the fellowship. In this article, we review key elements of
      a breast imaging fellowship to ensure that programs graduate radiologists that
      are well prepared to practice safely and independently. Such a program would
      provide a developmental framework using the Dreyfus model of skill acquisition.
      The training should be comprised of multiple and varied opportunities that
      promote active learning with appropriate supervision but progressive
      independence. SUMMARY: A successful fellowship program in breast imaging should
      embrace developmental milestones to ensure mastery of both basic and complex
      skills. Organized rotations, regular feedback, structured and self-directed
      learning activities, and participation in local, regional, and national meetings
      and organizations contribute to well-rounded graduates.

PMID- 30120046
TI  - Effects of theta burst stimulation of the left dorsolateral prefrontal cortex in
      disorders of consciousness.

PMID- 30120047
TI  - Cutaneous and Gastrointestinal Leukocytoclastic Vasculitis Induced by Palbociclib
      in a Metastatic Breast Cancer Patient: A Case Report.

PMID- 30120049
TI  - This Gift Requires Your Response.

PMID- 30120048
TI  - Insulin resistance is associated with Sfrp5 in obstructive sleep apnea.
AB  - INTRODUCTION: Obstructive sleep apnea, a common disease, is usually complicated
      by insulin resistance and type 2 diabetes mellitus. Adipokine is considered to
      play an important role in the development of insulin resistance and type 2
      diabetes mellitus in obstructive sleep apnea. OBJECTIVE: To assess whether
      secreted frizzled-related protein 5, a new adipokine, is involved in untreated
      obstructive sleep apnea patients. METHODS: Seventy-six subjects with obstructive
      sleep apnea and thirty-three control subjects without obstructive sleep apnea
      were recruited and matched in terms of body mass index and age. The fasting
      secreted frizzled-related protein 5 plasma concentration was tested using ELISA.
      In addition, the correlation between secreted frizzled-related protein 5 and the
      homeostasis model assessment of insulin resistance was obtained. Multiple linear
      regression analysis models with stepwise selection were performed to determine
      the independent associations between various factors and secreted frizzled
      related protein 5. RESULTS: Plasma secreted frizzled-related protein 5 levels
      were significantly lower in the obstructive sleep apnea group than in the control
      group (obstructive sleep apnea group: 28.44+/-13.25ng/L; control group: 34.16+/
      13.51ng/L; p=0.023). In addition, secreted frizzled-related protein 5 was
      negatively correlated with homeostasis model assessment of insulin resistance but
      positively correlated with the mean and lowest oxygen saturation with or without
      adjusting for age, gender, body mass index, neck circumference, waist
      circumference and waist-to-hip ratio. The multiple linear regression analysis
      showed there was an independent negative association between secreted frizzled
      related protein 5 and homeostasis model assessment of insulin resistance.
      CONCLUSION: Secreted frizzled-related protein 5 was involved in obstructive sleep
      apnea and the decrease in secreted frizzled-related protein 5 was directly
      proportional to the severity of obstructive sleep apnea. There was an independent
      negative correlation between homeostasis model assessment of insulin resistance
      and secreted frizzled-related protein 5 in the obstructive sleep apnea group.
      Secreted frizzled-related protein 5 might be a therapeutic target for insulin
      resistance in obstructive sleep apnea.

PMID- 30120050
TI  - Building a Tree From the Leaves Down: A Challenge for Contemporary Educators.

PMID- 30120039
TI  - Absolute risk and predictors of the growth of acute spontaneous intracerebral
      haemorrhage: a systematic review and meta-analysis of individual patient data.
AB  - BACKGROUND: Intracerebral haemorrhage growth is associated with poor clinical
      outcome and is a therapeutic target for improving outcome. We aimed to determine
      the absolute risk and predictors of intracerebral haemorrhage growth, develop and
      validate prediction models, and evaluate the added value of CT angiography.
      METHODS: In a systematic review of OVID MEDLINE-with additional hand-searching of
      relevant studies' bibliographies- from Jan 1, 1970, to Dec 31, 2015, we
      identified observational cohorts and randomised trials with repeat scanning
      protocols that included at least ten patients with acute intracerebral
      haemorrhage. We sought individual patient-level data from corresponding authors
      for patients aged 18 years or older with data available from brain imaging
      initially done 0.5-24 h and repeated fewer than 6 days after symptom onset, who
      had baseline intracerebral haemorrhage volume of less than 150 mL, and did not
      undergo acute treatment that might reduce intracerebral haemorrhage volume. We
      estimated the absolute risk and predictors of the primary outcome of
      intracerebral haemorrhage growth (defined as >6 mL increase in intracerebral
      haemorrhage volume on repeat imaging) using multivariable logistic regression
      models in development and validation cohorts in four subgroups of patients, using
      a hierarchical approach: patients not taking anticoagulant therapy at
      intracerebral haemorrhage onset (who constituted the largest subgroup), patients
      taking anticoagulant therapy at intracerebral haemorrhage onset, patients from
      cohorts that included at least some patients taking anticoagulant therapy at
      intracerebral haemorrhage onset, and patients for whom both information about
      anticoagulant therapy at intracerebral haemorrhage onset and spot sign on acute
      CT angiography were known. FINDINGS: Of 4191 studies identified, 77 were eligible
      for inclusion. Overall, 36 (47%) cohorts provided data on 5435 eligible patients.
      5076 of these patients were not taking anticoagulant therapy at symptom onset
      (median age 67 years, IQR 56-76), of whom 1009 (20%) had intracerebral
      haemorrhage growth. Multivariable models of patients with data on antiplatelet
      therapy use, data on anticoagulant therapy use, and assessment of CT angiography
      spot sign at symptom onset showed that time from symptom onset to baseline
      imaging (odds ratio 0.50, 95% CI 0.36-0.70; p<0.0001), intracerebral haemorrhage
      volume on baseline imaging (7.18, 4.46-11.60; p<0.0001), antiplatelet use (1.68,
      1.06-2.66; p=0.026), and anticoagulant use (3.48, 1.96-6.16; p<0.0001) were
      independent predictors of intracerebral haemorrhage growth (C-index 0.78, 95% CI
      0.75-0.82). Addition of CT angiography spot sign (odds ratio 4.46, 95% CI 2.95
      6.75; p<0.0001) to the model increased the C-index by 0.05 (95% CI 0.03-0.07).
      INTERPRETATION: In this large patient-level meta-analysis, models using four or
      five predictors had acceptable to good discrimination. These models could inform
      the location and frequency of observations on patients in clinical practice,
      explain treatment effects in prior randomised trials, and guide the design of
      future trials. FUNDING: UK Medical Research Council and British Heart Foundation.

PMID- 30120051
TI  - Implementation of smart phones to facilitate in-hospital telephone communication:
      Challenges, successes and lessons from a neonatal intensive care unit.
AB  - Implementation Lessons 1. Mobile telephony use in the hospital setting is complex
      and sub-optimal implementation of mobile communication technology can create
      inefficiencies in clinical workflow 2. Objective measurement of mobile
      technology's impact on clinical communication workflow is necessary to identify
      and remediate associated inefficiencies in real-time 3. Functionality between
      mobile applications and devices should be evaluated when implementing technology,
      particularly when an application is non-native to a device 4. Continual
      collaboration between front-line clinicians and technical teams allows for early
      identification of adverse impacts from, and optimization of, mobile communication
      technology implementation.

PMID- 30120052
TI  - Eurycoma longifolia, a promising suppressor of RANKL-induced differentiation and
      activation of osteoclasts: An in vitro mechanistic evaluation.
AB  - BACKGROUND: Eurycoma longifolia (E. longifolia) has gained remarkable recognition
      due to its promising efficacy of stimulating bone formation in androgen-deficient
      osteoporosis. Numerous in vivo studies have explored the effects of E. longifolia
      on osteoporosis; however, the in vitro cellular mechanism was not discovered yet.
      OBJECTIVES: The present study was aimed to investigate the effect of E.
      longifolia on the proliferation, differentiation and maturation of osteoclasts
      and the translational mechanism of inhibition of osteoclastogenesis using RAW
      264.7 cells as an in vitro osteoclastic model. MATERIALS AND METHODS: Having
      assessed cytotoxicity, the cell viability, cell proliferation rate and
      osteoclastic differentiation capacity of E. longifolia was investigated by
      evaluating the tartrate-resistant acid phosphatase (TRAP) activity in receptor
      activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced
      osteoclasts. Taken together, the time-mannered expression of osteoclast-related
      protein biomarkers such as matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP,
      nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), superoxide (free
      radicals) generation and superoxide dismutase activity were also measured to
      comprehend the mechanism of osteoclastogenesis. RESULTS: E. longifolia did not
      show significant effects on cytotoxicity and cell proliferation of RAW 264.7
      cells; however, a significant inhibition of cells differentiation and maturation
      of osteoclasts was observed. Moreover, a significant down-regulation of RANKL
      induced TRAP activity and expression of MMP-9, cathepsin-K, TRAP, NFATc1 and
      generation of superoxide and enhanced superoxide dismutase activity was observed
      in E. longifolia treated cell cultures. CONCLUSION: We anticipated that E.
      longifolia that enhances bone regeneration on the one hand and suppresses
      osteoclast's maturation on the other hand may have great therapeutic value in
      treating osteoporosis and other bone-erosive diseases such as rheumatoid
      arthritis and metastasis associated with bone loss.

PMID- 30120053
TI  - HPLC characterization of molluscicidal component of Tamarindus indica and its
      mode of action on nervous tissue of Lymnaea acuminata.
AB  - BACKGROUND: Fasciolosis is a water-borne disease with gastropods snail (Lymnaea
      acuminata) act as key-link is still burden for mankind especially in developing
      countries. Snail control is one of the important tools to trim down the frequency
      of fasciolosis. OBJECTIVE: To evaluate the toxic effect and inhibitory potential
      of plant Tamarindus indica and their active constituent on the key enzyme of
      nervous tissue of snail L. acuminata. METHOD: The present study deals with the
      chromatographic isolation and identification of molluscicidal component from
      Tamarindus indica bark and its effects on enzymes activities of vector snail L.
      acuminata. RESULT: The toxicity study reveals that among all organic extract
      ethanol extract of T. indica bark (96 h LC50:127.4 mgL-1) was more effective than
      other organic extracts. The 96 h LC50 of column purified fraction of T. indica
      bark was 13.78 mgL-1 respectively. Saponin was isolated, characterized and
      identified as active molluscicidal component in the bark of T. indica by column
      chromatography, TLC and HPLC chromatographic methods. The in vivo and in vitro
      treatment of column purified fraction and saponin has significant inhibition in
      enzyme AChE, ACP and ALP activities. The study of inhibition kinetics indicates
      that inhibition of AChE and ALP is competitive, while ACP is uncompetitive in
      both the treatments. CONCLUSION: Thus inhibition of these enzyme activities by T.
      indica bark column purified fraction and saponin in the snail L. acuminata may be
      the cause of its molluscicidal activity which leads snail death.

PMID- 30120054
TI  - Integration of traditional herbal medicines among the indigenous communities in
      Thiruvarur District of Tamil Nadu, India.
AB  - BACKGROUND: Ethnobotanical studies are recognized as effective methods of finding
      locally important plants for discovery of crude drugs. Siddha medicinal system is
      prevailed in south Indian states principally in Tamil Nadu and gaining
      recognition as alternative medicine among the indigenous communities for their
      primary healthcare needs. OBJECTIVES: The study was aimed to explore and document
      folk medicinal plant knowledge among the local people in Puliyankudi village of
      Thiruvarur District, Tamil Nadu, India. MATERIALS AND METHODS: An ethnobotanical
      study was carried out during February 2016 to January 2017 among the local people
      in study area. Traditional healers, traders, local vendors and local people who
      are practicing herbal medicines were approached for documentation of folk
      medicinal uses. Acquired results were further analyzed with descriptive
      statistical methods such as use value (UV) and informant consensus factor (ICF).
      RESULTS: During the survey, a total 116 plant species from 49 families and 103
      genera were recorded to treat 73 types of ailments. Among the plant parts used
      for preparation of medicine, leaves (73 reports) are often used and predominant
      method of preparation of medicine is paste (56 reports). Limonia acidissima was
      reported by all the interviewed informants with an UV of 0.98 and kidney problems
      have highest ICF value of 0.91. CONCLUSION: Plants with highest use values in the
      study indicates possible occurrence of valuable metabolites and should be
      investigated for associated pharmacological activities which leads to development
      of potential new drugs to treat various ailments.

PMID- 30120055
TI  - Acute oral toxicity and anti-inflammatory evaluation of methanolic extract of
      Rotula aquatica roots in Wistar rats.
AB  - BACKGROUND: The plant Rotula aquatica Lour. was traditionally well known due to
      its large number of pharmacological action and medicinal uses. The plant is a
      necessary component of many Ayurvedic drug preparations since historical times.
      It is widely used as a crucial ancient drug for kidney and bladder stones.
      OBJECTIVES: The main objective of the study was to evaluate the acute toxicity
      and anti inflammatory efficacy of methanolic extract of R.aquatica Lour. in in
      vivo models. MATERIALS AND METHODS: The qualitative phytochemical analysis and
      invitro antioxidant activity of the roots of methanolic extract of R.aquatica
      Lour. (MERA) was evaluated. The acute toxicity effect of MERA was evaluated with
      two different doses (550, 2000 mg/kg body weight), were administrated orally to
      Wistar rats. The rats were observed for sign and symptoms of toxicity and
      mortality for 14 days. The parameters measured including relative organ weight,
      blood, biochemical and histopathological parameters of hepatic and renal
      toxicity. The anti-inflammatory effect of MERA was also evaluated in carrageenan
      and dextran-induced paw edema models. RESULTS: The phytochemical evaluation of
      MERA shows the presence of secondary metabolites like alkaloids, flavonoids,
      phenolics and tannins, phytosterols, reducing sugars, proteins and terpenoids.
      The results of in-vitro antioxidant evaluation of MERA reveal its capability to
      scavenging free radical at a lower concentration. The MERA did not show any
      visible signs of toxicity up to the dose of 2000 mg/kg body weight. The results
      obtained from our carrageenan and dextran-induced paw edema model study also
      proved the anti-inflammatory effect of MERA in rat model. CONCLUSION: The result
      shows the potential of MERA as an anti-inflammatory drug to reduce the signs of
      inflammation devoid of any toxic effect.

PMID- 30120056
TI  - Holistic assessment of anger in adolescents - Development of a rating scale.
AB  - BACKGROUND: Anger related issues in adolescents are an important contributor to
      adolescent mortality and many negative developmental outcomes. Anger being the
      most primitive defence mechanism, determining its maladaptive nature is a complex
      phenomenon. Further, it lacks clarity in terms of its definition, demarcation
      from aggression and hostility, and also its assessment. Available anger rating
      scales do not represent anger adequately or comprehensively. The concept of anger
      is dealt with exhaustively in Indian classical texts. According to these texts,
      anger is an evil virtue that is born out of Rajasic nature and leads to momentary
      loss of cognitive functional abilities. Manifestation of anger occurs at
      behavioural (kayika), verbal (vachika) and mental (manasika) levels. Based on
      these principles, a psychometric scale is developed for assessment of anger in
      adolescents. OBJECTIVE: The objective of this study was to develop a psychometric
      scale for assessment of anger in adolescents based on behavioural (kayika),
      verbal (vachika) and mental (manasika) levels. MATERIALS & METHODS: Item
      generation was done referring to the existing scales, texts on spirituality and
      psychology. It also included discussions with children, teachers and parents.
      Item reduction was carried out using expert opinion, focused group discussion and
      factor analysis. Testretest reliability was checked with 127 children (63 girls
      and 64 boys). The final scale was administered to 757 children (427 girls and 330
      boys) to ascertain reliability co-efficient values. RESULTS: Co-efficient of
      Alpha value for final scale recorded 0.804. Test-retest reliability showed .835
      correlation. CONCLUSION: Anger can be assessed holistically using Trikarana
      (kayika, vachika and manasika) concept as dealt in almost all Indian classical
      texts. A 23-item adolescent anger scale is a comprehensive tool to assess
      behavioural, verbal and mental anger in adolescents.

PMID- 30120057
TI  - Protective efficacy of Chlorophytum borivilianum root extract against murine
      visceral leishmaniasis by immunomodulating the host responses.
AB  - BACKGROUND: The available drugs for treating visceral leishmaniasis are limited.
      Moreover, the disease is associated with suppression of immune function.
      Therefore, therapies with effective immunomodulatory agents are needed which can
      decrease parasitic burden and enhance adaptive immunity. OBJECTIVES: The present
      study was planned to evaluate the antileishmanial efficacy of crude ethanolic
      extract of roots of Chlorophytum borivilianum (CBREE) against murine visceral
      leishmaniasis through immunomodulation. MATERIALS AND METHODS: The in vitro
      studies were carried out to check leishmanicidal activity against promastigote
      form and cytotoxicity against HeLa cells. The parasite load in liver smears,
      immunological and biochemical changes induced by 500 and 1000 mg/kg b.wt. of
      CBREE were assessed on 1, 7, 14 and 21 post treatment days in infected and
      treated BALB/c mice. RESULTS: CBREE showed inhibitory effect on growth of
      promastigotes with IC50 of 28.25 MUg/mL and negligible cytotoxicity. The extract
      was toxicologically safe in BALB/c mice when administered orally with 5 g/kg
      b.wt. of extract. A significant reduction in parasite load was observed along
      with active immunomodulation through enhanced Th1 type of immune responses and
      suppressed Th2 type of immune responses. CONCLUSION: The treatment with both
      doses showed no toxic effect as evidenced by normal liver and kidney function
      tests and normal histological observations of liver and kidney. Therefore, it
      should be further explored for its active components in pursuit of the new
      effective antileishmanial agents in the plant kingdom.

PMID- 30120058
TI  - Antioxidant and antibacterial activity of silver nanoparticles synthesized by
      Cestrum nocturnum.
AB  - BACKGROUND: Silver nanoparticles are toxic to bacteria and have widespread
      application in different research areas. OBJECTIVE: The aim of this study was to
      synthesize silver nanoparticles using an aqueous leaf extract of Cestrum
      nocturnum and to test its antioxidant and antibacterial activities. MATERIALS AND
      METHODS: The silver nanoparticles were synthesized by addition of 20 ml extract
      (8% w/v) with 180 ml silver nitrate solution (1 mM). The synthesis of silver
      nanoparticles was confirmed by UV-Vis spectrophotometer. The silver nanoparticles
      were characterized by X-ray diffractometer, Transmission Electron Microscope,
      Scanning Electron Microscope and Fourier Transform Infra-Red spectroscopy. The
      antioxidant property of silver nanoparticles was analyzed by the 2, 2-diphenyl-1
      picrylhydrazyl, hydrogen peroxide, hydroxyl radical and superoxide radical
      scavenging methods. The bacteriostatic and bactericidal activity of silver
      nanoparticles against Escherichiacoli, Enterococcusfaecalis, and Salmonellatyphi
      was determined using bacterial growth inhibition method. The antibacterial
      sensitivity and Minimum Inhibitory Concentration (MIC) of silver nanoparticles
      was determined against the bacteria. RESULTS: The results confirmed that the
      silver nanoparticles synthesized by C.nocturnum extract were crystalline in
      nature, average particle size was 20 nm and were mostly spherical in shape. The
      antioxidant methods confirmed that the silver nanoparticles have more antioxidant
      activity as compared to vitamin C. The silver nanoparticles have strong
      antibacterial (maximum Vibrio cholerae and minimum E. faecalis) activity. The MIC
      value of silver nanoparticles was 16 MUg/ml (Citrobacter), 4 MUg/ml (E.
      faecalis), 16 MUg/ml (S. typhi), 8 MUg/ml (E. coli), 8 MUg/ml (Proteusvulgaris),
      and 16 MUg/ml (V. cholerae). CONCLUSION: Green synthesized silver nanoparticles
      have strong antioxidant and antibacterial activity due to the presence of
      bioactive molecules on the surface of silver nanoparticles.

PMID- 30120060
TI  - T Cell Tumor Immunotherapy: Oncolysis Beats Lymphodepletion.

PMID- 30120059
TI  - Exosome-Derived miR-130a Activates Angiogenesis in Gastric Cancer by Targeting C
      MYB in Vascular Endothelial Cells.
AB  - Metastasis is a crucial reason for the poor prognosis of gastric cancer.
      Angiogenesis is closely associated with tumor invasion and metastasis. Cancer
      derived exosomes play an important role in the establishment of the tumor
      microenvironment. In this study, exosomes were isolated by sequential
      differential centrifugation, and they were verified by transmission electron
      microscopy. Changes in the biological behavior of human umbilical vein
      endothelial cells were evaluated with downstream cellular functional experiments.
      The RNA and protein levels of the miRNA target gene were determined by real-time
      qPCR and western blotting. A mouse xenograft model was adopted to evaluate the
      correlation between exosome-derived miR-130a and tumor growth in vivo. We
      demonstrated that exosomes delivered miR-130a from gastric cancer cells into
      vascular cells to promote angiogenesis and tumor growth by targeting c-MYB both
      in vivo and in vitro. miR-130a packaged in exosomes secreted from cancer cells
      acts as a driver of angiogenesis. Therefore, miR-130a might be a potential
      biomarker for monitoring the activity of gastric cancer. In addition, suppressing
      the expression or blocking the transmission of these exosomes might be a novel
      antiangiogenic therapeutic strategy for gastric cancer.

PMID- 30120061
TI  - Oocytes from stem cells.
AB  - Folliculogenesis describes the process of activating an oocyte-containing
      primordial follicle from the ovarian reserve and its development to the mature
      ovulatory stage. This process is highly complex and is controlled by extra- and
      intra-ovarian signaling events. Oocyte competence and capacity for fertilization
      to support a viable pregnancy are acquired during folliculogenesis. Cancer and
      cancer-based therapies can negatively affect this process, compromising
      fertility. Currently, preservation of fertility in these patients remains limited
      to surrogacy, oocyte freezing, oocyte donation, or in vitro maturation (IVM).
      Recent reports of stem cells being used to produce fully competent oocytes and
      subsequently healthy offspring in mice have opened up a novel avenue for
      fertility preservation. However, translating these findings into human health
      first relies on enhancing our understanding of follicle growth and mimicking its
      intricacies in vitro. Indeed, the future of oocytes from stem cells in humans
      comes with many possibilities but currently faces several technical and ethical
      obstacles.

PMID- 30120062
TI  - Intimate Relationships and Sexual Behavior in Young Women withDepression.
AB  - PURPOSE: To better understand links between depressive symptoms and high-risk
      sexual behavior in young women. METHODS: We conducted semistructured interviews
      with young women from three primary care clinics who reported clinically
      significant depressive symptoms, had penile-vaginal sexual intercourse within the
      past 6 months, and met at least one sexual risk criterion (N = 16, age 16
      23years, racially/ethnically diverse). We transcribed the interview recordings,
      organized and coded the data, and conducted a directed content analysis. RESULTS:
      Participants described a complex interrelation between depression and intimate
      relationships and sexual behavior. Depression had negative effects on
      relationships, sexual motives and experiences (including safety), and feelings
      about oneself in sexual situations. Participants reported difficulty in
      developing and maintaining intimate relationships. Although many participants
      reported less interest in and emotional energy for sex, several were having sex
      frequently to manage depressive symptoms. Generally, the young women described
      sex as unsafe (e.g., no condom) owing to impaired judgment, increased
      impulsivity, apathy, and alcohol. As a result, sometimes their efforts to feel
      better by having sex led them to feeling worse (e.g., ashamed and worthless).
      CONCLUSIONS: Depressed young women may limit intimate relationships, yet engage
      in frequent and unsafe sex to cope with their symptoms. Their efforts to feel
      better may provide only temporary relief or result in feeling worse. Depressed
      young women would benefit from tailored interventions that identify and counter
      unhealthy thoughts, attitudes, behaviors, and patterns related to sexual
      relationships and behavior; minimize factors that impair healthy decision-making;
      and foster development of alternative affect regulation strategies.

PMID- 30120063
TI  - Body Image Dissatisfaction and the Adrenarchal Transition.
AB  - BACKGROUND: Puberty marks a transition in risk for body image disturbance and
      disordered eating. Yet few studies have examined these symptoms across puberty
      and none have examined links with adrenarche, the earliest phase in the pubertal
      hormonal cascade. METHOD: Levels of adrenal androgens (dehydroepiandrosterone,
      dehydroepiandrosterone sulphate, and testosterone) were measured in a population
      based study of 8- to 9-year-old children (516 males and 621 females). Body
      dissatisfaction was measured using the Kids' Eating Disorder Scale Silhouettes.
      Covariates included body mass index, age, and socioeconomic status. RESULTS:
      There were significant associations between adrenal androgen levels and greater
      body dissatisfaction in both males and females. Specifically, females with more
      advanced levels of dehydroepiandrosterone and testosterone relative to peers, and
      males with more advanced levels of testosterone relative to peers, reported
      greater body dissatisfaction. However, after adjusting for covariates, hormones
      levels were no longer associated with body dissatisfaction, and only higher body
      mass index had a clear association with body dissatisfaction. CONCLUSIONS: The
      adrenarchal transition brings a heightened risk for body dissatisfaction. Whether
      this arises from the neuroendocrine effects of adrenal androgens or as a reaction
      to the greater body mass that accompanies adrenarche requires further
      exploration.

PMID- 30120065
TI  - The Safety Level of Total Central Venous Access Port Implantation Performed by
      Residents.
AB  - OBJECTIVE: The implantation of totally implantable venous access ports (TIVAPs)
      is one of the first procedures surgical residents learn. Complications after
      implantation procedures have a major impact on patient outcomes, as it may lead
      to a delay of chemotherapy regimens or of parenteral nutrition. The aim of this
      study was to compare the outcomes after totally implantable venous access ports
      implantations done by resident and attending surgeons. DESIGN: The study was
      performed as a retrospective analysis. SETTING: The study took place in primary
      care at the Department of General and Visceral Surgery at Frankfurt University
      Hospital. PARTICIPANTS: A total of 760 primary totally implantable venous access
      ports implantations performed between March 2008 and December 2016 were included
      in a database. Three groups of surgeons doing the implantations were defined:
      Group A (residents alone), Group B (resident with help), and Group C (attending
      surgeons). RESULTS: There was a significant difference between the surgeon groups
      in operation time (p < 0.001). The groups differed between Group A (mean, 49; SD,
      22) and Group C (mean, 39; SD, 20); p < 0.001) and Group B (mean, 53; SD, 23) and
      Group C (mean, 39; SD, 20; p < 0.001). The incidence of surgical site infections
      between Groups A and C (3.6% vs. 0.3%; p = 0.003) and Groups B and C (2.5% vs.
      0.3%; p = 0.027) differed also significantly. Based on multivariable logistic
      regression analysis operation time in minutes (OR, 1.04; 95%CI, 1.03-1.06; p <
      0.001) was an independent risk factor for any intraoperative complications. For
      any postoperative complications younger age of the patient (OR, 0.98; 95%CI, 0.97
      0.99; p = 0.004) and benign primary disease (OR, 3.25; 95%CI, 1.55-6.64; p =
      0.002) were independent risk factors based on multivariable regression analysis.
      Based on multivariable regression analysis a lower body mass index of the patient
      (OR, 0.93; 95%CI, 0.86-0.99; p = 0.044), benign primary disease (OR, 2.89; 95%CI,
      1.07-7.79; p = 0.036), and no chemotherapy (OR, 3.55; 95%CI, 1.50-8.39; p =
      0.004) were independent risk factors for postoperative catheter infections.
      Surgeon group was no risk factor, neither for intraoperative and postoperative
      complications, nor for catheter explantation due to complications. CONCLUSION:
      Residents performing alone or residents performing with help can safely handle a
      central venous access port implantation. In patients with several risk factors,
      however, an attending should assist.

PMID- 30120066
TI  - Clinical efficacy of the Toll-like receptor 9 agonist cobitolimod using patient
      reported-outcomes defined clinical endpoints in patients with ulcerative colitis.
AB  - BACKGROUND: The Toll-like-receptor 9 (TLR-9) agonist cobitolimod (DIMS0150,
      Kappaproct(r)) is a promising therapeutic option for ulcerative colitis (UC)
      patients. AIMS: The objectives of this post-hoc analysis using the COLLECT study
      data was to investigate the clinical effects of cobitolimod using patient
      reported-outcomes (PRO) defined endpoints. METHODS: Dual topical administration
      of cobitolimod was studied in a randomised, multicentre clinical trial named
      COLLECT in moderate-to-severe UC patients. Symptomatic remission (SR) was studied
      in 104 patients based on their e-diary records and was defined as absence of
      blood in stool and a mean daily stool frequency (SF) < 4. RESULTS: SR was
      achieved at week 4 in 17.1% of cobitolimod vs. 5.9% of placebo treated patients
      (p = 0.13), at week 8 in 35.7% vs. 17.6% (p = 0.07), and at week 12 in 38.6% vs.
      17.6% (p = 0.04) of the patients, respectively. SR rates with cobitolimod and
      placebo in anti-TNFalpha experienced patients were smaller but with a broadly
      similar relative effect-size to anti-TNFalpha naive patients. Clinical efficacy
      was higher in patients with moderate compared to severe disease. CONCLUSIONS:
      Application of the Toll-like-receptor 9 (TLR-9) agonist cobitolimod is able to
      induce remission as assessed by PRO measures in UC patients with moderate-to
      severe activity as well as in anti-TNFalpha experienced and naive patients
      supporting the overall efficacy of the substance.

PMID- 30120064
TI  - Intestinal bitter taste receptor activation alters hormone secretion and imparts
      metabolic benefits.
AB  - OBJECTIVES: Extracts of the hops plant have been shown to reduce weight and
      insulin resistance in rodents and humans, but elucidation of the mechanisms
      responsible for these benefits has been hindered by the use of heterogeneous hops
      derived mixtures. Because hop extracts are used as flavoring agents for their
      bitter properties, we hypothesized that bitter taste receptors (Tas2rs) could be
      mediating their beneficial effects in metabolic disease. Studies have shown that
      exposure of cultured enteroendocrine cells to bitter tastants can stimulate
      release of hormones, including glucagon-like peptide 1 (GLP-1). These findings
      have led to the suggestion that activation of Tas2rs may be of benefit in
      diabetes, but this tenet has not been tested. Here, we have assessed the ability
      of a pure derivative of a hops isohumulone with anti-diabetic properties, KDT501,
      to signal through Tas2rs. We have further used this compound as a tool to
      systematically assess the impact of bitter taste receptor activation in obesity
      diabetes. METHODS: KDT501 was tested in a panel of bitter taste receptor
      signaling assays. Diet-induced obese mice (DIO) were dosed orally with KDT501 and
      acute effects on glucose homeostasis determined. A wide range of metabolic
      parameters were evaluated in DIO mice chronically treated with KDT501 to
      establish the full impact of activating gut bitter taste signaling. RESULTS: We
      show that KDT501 signals through Tas2r108, one of 35 mouse Tas2rs. In DIO mice,
      acute treatment stimulated GLP-1 secretion and enhanced glucose tolerance.
      Chronic treatment caused weight and fat mass loss, increased energy expenditure,
      enhanced glucose tolerance and insulin sensitivity, normalized plasma lipids, and
      induced broad suppression of inflammatory markers. Chronic KDT501 treatment
      altered enteroendocrine hormone levels and bile acid homeostasis and stimulated
      sustained GLP-1 release. Combined treatment with a dipeptidyl peptidase IV
      inhibitor amplified the incretin-based benefits of this pure isohumulone.
      CONCLUSIONS: Activation of Tas2r108 in the gut results in a remodeling of
      enteroendocrine hormone release and bile acid metabolism that ameliorates
      multiple features of metabolic syndrome. Targeting extraoral bitter taste
      receptors may be useful in metabolic disease.

PMID- 30120067
TI  - [Pheochromocytoma and pregnancy: About one case].

PMID- 30120068
TI  - Renogram in kidney transplant. Utility of delayed images with SPECT/CT in the
      diagnosis of urinary leak.
AB  - Urinary leakage in patients with kidney transplantation is a relatively common
      surgical complication that requires early diagnosis and intervention. The
      isotopic renogram is a non-invasive and effective method to evaluate the
      perfusion and function of kidney transplantation, and allows us to diagnose
      urological complications such as urinary leakage. In these cases, it is useful to
      complete the study with planar images and delayed SPECT/CT to specify the
      diagnosis and locate the leak. We expose two cases diagnosed with urinary leak
      after performing a renogram with early and delayed planar images and delayed
      SPECT/CT a week after transplantation. In both cases, a percutaneous nephrostomy
      catheter was placed, as well as a double J catheter, resolving the surgical
      complication.

PMID- 30120070
TI  - NmCV-5 meningococcal vaccine: Neisseria meningitidis' nemesis?

PMID- 30120069
TI  - Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine
      containing serogroups A, C, Y, W, and X in healthy adults: a phase 1, single
      centre, double-blind, randomised, controlled study.
AB  - BACKGROUND: Invasive meningococcal disease is an important public health problem,
      especially in sub-Saharan Africa. After introduction of MenAfriVac in 2010,
      Neisseria meningitidis serogroup A disease has been almost eliminated from the
      region. However, serogroups C, W, Y, and X continue to cause disease outbreaks.
      We assessed the NmCV-5 pentavalent meningococcal conjugate vaccine targeting A,
      C, Y, W, and X serogroups in a first-in-man, phase 1 study. METHODS: We did a
      single-centre, double-blind, randomised controlled trial at a research clinic in
      Baltimore (MD, USA). Participants were healthy adults aged 18-45 years with no
      history of meningococcal vaccination or previous meningococcal infection. We
      randomly assigned participants (1:1:1) by an SAS-generated random schedule to a
      single, 0.5 mL, intramuscular injection of aluminium-phosphate adjuvanted NmCV-5,
      non-adjuvanted NmCV-5, or control (the quadrivalent meningococcal conjugate
      vaccine Menactra). The randomisation sequence used a permuted block design with
      randomly chosen block sizes of three and six. The vaccines were prepared,
      labelled, and administered with procedures to ensure participants and study
      personnel remained masked to treatment. After vaccination, participants were
      observed in the clinic for 60 min for adverse reactions. Participants recorded
      daily temperature and injection site or systemic reactions at home and returned
      to the clinic for follow-up visits on days 7, 28, and 84 for safety assessments;
      blood samples were also collected on day 7 for safety laboratory assessment. A
      phone call contact was made 6 months after vaccination. Serum was collected
      before vaccination and 28 days after vaccination for immunological assessment
      with a rabbit complement-dependent serum bactericidal antibody (rSBA) assay. The
      primary objective was an intention-to-treat assessment of safety, measuring local
      and systemic reactogenicity over 7 days, unsolicited adverse events through 28
      days, and serious adverse events over 6 months. The secondary objective for the
      assessment of immunogenicity, was a per-protocol analysis of rSBA before and 28
      days after vaccination. This trial is registered with ClinicalTrials.gov, number
      NCT02810340. FINDINGS: Between Aug 17, 2016, and Feb 16, 2017, we assigned 20
      participants to each vaccine. All vaccines were well-tolerated. Pain was the most
      common local reaction, occurring in 12 (60%), ten (50%), and seven (35%)
      participants in the adjuvanted NmCV-5, non-adjuvanted NmCV-5, and control groups,
      respectively. Headache was the most common systemic reaction, occurring in five
      (25%), three (15%), and three (15%), respectively. Most solicited reactogenicity
      adverse reactions were mild (60 [74%] of 81) and all were self-limiting. None of
      the differences in proportions of individuals with each solicited reaction was
      significant (p>0.300 for all comparisons) between the three vaccination groups.
      There were no serious adverse events and 19 unsolicited non-serious adverse
      events in 14 (23%) participants. Both adjuvanted and non-adjuvanted NmCV-5
      elicited high rSBA titres against all five meningococcal serogroups. The pre
      vaccination geometric mean titres (GMTs) ranged from 3.36 to 53.80 for the
      control, from 6.28 to 187.00 for the adjuvanted vaccine, and from 4.29 to 350.00
      for the non-adjuvanted vaccine, and the post-vaccination GMT ranged from 3.14 to
      3214 for the control, from 1351 to 8192 for the adjuvanted vaccine, and from 1607
      to 11 191 for the non-adjuvanted vaccine. Predicted seroprotective responses (ie,
      an increase in rSBA titres of eight times or more) for the adjuvanted and non
      adjuvanted NmCV-5 were similar to control responses for all five serogroups.
      INTERPRETATION: The adjuvanted and non-adjuvanted NmCV-5 vaccines were well
      tolerated and did not produce concerning adverse effects and resulted in immune
      responses that are predicted to confer protection against all five targeted
      serogroups of invasive meningococcal disease. Further clinical testing of NmCV-5
      is ongoing, and additional clinical trials are necessary to confirm the safety
      and immunogenicity of NmCV-5 in target populations. FUNDING: UK Department for
      International Development.

PMID- 30120071
TI  - Patterns of antiepileptic drug use in patients with potential refractory epilepsy
      in Texas Medicaid.
AB  - OBJECTIVES: Antiepileptic drug (AED) monotherapy is usually effective in 60% of
      the patients with epilepsy while the remaining patients have refractory epilepsy.
      This study compared treatment patterns (adherence, persistence, addition, and
      switching) associated with refractory and nonrefractory epilepsy. METHODS: Texas
      Medicaid claims from 09/01/07-12/31/13 were analyzed, and patients eligible for
      the study 1) were between 18 and 62 years of age, 2) had a prescription claim for
      an AED during the identification period (03/01/08-12/31/11) with no prior
      baseline AED use (6-month), and 3) had evidence of epilepsy diagnosis within 6
      months of AED use. Based on AED use in the identification period, patients were
      categorized into "refractory" (>=3AEDs) and "nonrefractory" (<3AEDs) cohorts. The
      index date was the date of the first AED claim. Patients in both cohorts were
      matched 1:1 using propensity scoring and compared for adherence (proportion of
      days covered (PDC) >=80% vs. <80%), persistence, addition (yes/no), and switching
      (yes/no) using multivariate conditional regression models. Conditional logistic
      regression and Cox proportional hazard models were used to address the study
      objectives. RESULTS: Of the 10,599 eligible patients, 2798 (26.5%) patients in
      the refractory cohort were matched to patients in the nonrefractory cohort.
      Patients in the refractory cohort had significantly higher (p < 0.005) mean (+/
      Standard deviation (SD)) adherence (88.6% (+/-19.1%) vs. 77.0% +/- (25.8%)) and
      persistence (328.0 (+/-87.3) days vs. 294.9 +/- (113.4) days) as compared with
      patients in the nonrefractory cohort. Compared with patients with nonrefractory
      epilepsy, patients with refractory epilepsy were 3.6 times (odds ratio (OR) =
      3.553; 95% confidence interval (CI) = 3.060-4.125; p < 0.0001) more likely to
      adhere to AEDs and had a 34.7% (hazard ratio (HR) = 0.653; 95% CI = 0.608-0.702;
      p < 0.0001) lower hazard rate of discontinuation of AEDs. Also, patients with
      refractory epilepsy were 3.7 times (OR = 3.723; 95% CI = 2.902-4.776; p < 0.0001)
      more likely to add an alternative AED and 3.6 times (OR = 3.591; 95% CI = 3.010
      4.284; p < 0.0001) more likely to switch to an alternative AED. CONCLUSION:
      Patients with refractory epilepsy were significantly more likely to adhere and
      persist to AED regimen and were significantly more likely to add and switch to an
      alternative AED than patients with nonrefractory epilepsy.

PMID- 30120072
TI  - Abnormal cortical activation during an auditory word comprehension task in benign
      childhood epilepsy with centrotemporal spikes: A magnetoencephalographic study.
AB  - OBJECTIVE: Benign childhood epilepsy with centrotemporal spikes (BECTS), also
      known as rolandic epilepsy, has recently been reported to be associated with
      variable degrees of cognitive dysfunction. Many studies reported poor language
      ability in children with BECTS compared with healthy control children. To
      elucidate the harmful effects of BECTS on language cognition, we studied the
      magnetoencephalographic activity elicited by an auditory language comprehension
      task. METHODS: The participants (N = 20) included 10 children diagnosed with
      BECTS (aged 10.8 +/- 2.8 years) and 10 age-matched healthy children (control)
      (aged 10.6 +/- 1.6 years). Cognitive function was assessed using general
      intellectual function and language ability. In patients with BECTS, we reviewed
      the clinical course and electroencephalogram (EEG) findings. We recorded the
      cortical responses elicited by an auditory language comprehension task using
      magnetoencephalography (MEG). We compared those results between groups and
      analyzed the correlation with cognitive scores and frequency of spikes. RESULTS:
      The full-scale intelligence quotient (FSIQ) by the Wechsler Intelligence Scale
      for Children-4th edition was significantly reduced in the group with BECTS (96.4
      +/- 12.3) compared with the control group (110.0 +/- 7.4). In half of the group
      with BECTS, the auditory comprehension score fell below the age-standard level.
      In the group with BECTS, the cortical activation during the task showed reduced
      intensity in language-associated areas such as the bilateral primary auditory
      cortex, left superior and mid-temporal areas, and inferior frontal area compared
      with those in the control group. In addition, the cortical activation in the left
      superior temporal area was negatively correlated with spike frequency and
      positively correlated with FSIQ in the group with BECTS. Conversely, the right
      inferior frontal and mid-temporal areas had increased the activations in the
      group with BECTS. From the time frequency analysis, low gamma band event-related
      desynchronization was reduced in the group with BECTS. CONCLUSION: Epileptic
      spikes negatively influenced responsiveness to the auditory language
      comprehension task in the language-associated cortices. These findings suggest
      that epileptic spikes could have a negative impact on the functional activity in
      rolandic areas and become a reason to change the functional development of the
      language network.

PMID- 30120073
TI  - Corrigendum to Pediatric Supratentorial Ganglioneuroblastoma: Case Report and
      Review of Literature [World Neurosurgery 113 (2018) 261-266].

PMID- 30120074
TI  - The Role of Radiolabeled Prostate-specific Membrane Antigen Positron Emission
      Tomography/Computed Tomography for the Evaluation of Renal Cancer.
AB  - CONTEXT: Preliminary results have demonstrated that prostate-specific membrane
      antigen (PSMA) is highly expressed on the cell surface of the microvasculature of
      several solid tumors, including renal cell carcinoma (RCC). OBJECTIVE: To assess
      the role of PSMA positron emission tomography (PET)/computed tomography (CT) in
      RCC patients and to discuss its possible inclusion in the clinical management of
      these patients. EVIDENCE ACQUISITION: A systematic literature search was
      performed for studies on PET/CT in patients with RCC up to April 2018. MEDLINE
      databases, such as Pubmed, Web of Science, and Scopus were consulted using the
      following keywords: "Renal Cell Carcinoma" AND "PET/CT", "Renal Cancer" AND
      "PET/CT", "renal cancer" AND "PSMA PET/CT", and "renal cell carcinoma" AND "PSMA
      PET/CT". EVIDENCE SYNTHESIS: Thirteen articles were retrieved from the available
      literature; the majority of them were relative to metastatic RCC (n=11/13, 85%)
      and eight of them were clinical cases, thus providing low-quality data. No
      diagnostic benefit of PSMA PET/CT was found in the evaluation of primary tumors.
      PSMA PET/CT may be a useful imaging modality in whole-body staging and restaging
      of patients with RCC and in the assessment of lesions that remained unclear on
      conventional imaging. Furthermore, PSMA PET/CT may predict the response to anti
      angiogenic-targeted therapies. CONCLUSIONS: The utility of PSMA-based PET imaging
      in the assessment of patients with RCC is encouraging. However, the available
      preliminary results will need to be addressed with larger prospective trials.
      PATIENT SUMMARY: In this mini-review, we evaluated the usefulness of an
      alternative imaging technique for patients with renal cell cancer. We found that
      this new imaging modality may indeed be useful. We conclude that the preliminary
      data should be assessed by larger studies.

PMID- 30120075
TI  - Robotic Partial Nephrectomy for Posterior Renal Tumours: Retro or Transperitoneal
      Approach?
AB  - The advantages of using the retroperitoneal approach in posterior and lateral
      masses are the familiarity and increased experience of the robotic surgeon with
      the nuances of this approach, which will ultimately benefit patients for whom
      that technique is imperative.

PMID- 30120076
TI  - Sex Disparities in Outcomes of Early Stage Colorectal Cancer: A Population-Based
      Study.
AB  - BACKGROUND: Women have been shown to experience longer overall survival after
      colorectal cancer (CRC) diagnosis than men even after adjusting for disease stage
      and management. However, the etiology of this observation is not well understood,
      and the impact of non-CRC health conditions on survival has not been described.
      We aimed to evaluate the prognostic role of sex on CRC-specific outcomes.
      PATIENTS AND METHODS: All patients who underwent primary resection of stage I to
      III CRC from 2001 to 2005, and who were referred to cancer centers in a large,
      representative Canadian province were reviewed. Baseline patient characteristics,
      including common comorbidities, were compared between men and women.
      Multivariable analysis was used to evaluate the associations between sex and
      survival outcomes. RESULTS: We identified 1837 patients. Median age was 69
      (interquartile range 60-76) years, and there were 867 women (47%) and 970 men
      (53%). Men were more likely to report ischemic heart disease, diabetes,
      dyslipidemia, and obesity (all P < .001). On multivariable analysis, men had
      worse overall and recurrence-free survival compared to women (hazard ratio [HR] =
      1.38, 95% confidence interval [CI] 1.15-1.64; and HR = 1.40, 95% CI, 1.18-1.67,
      respectively). However, CRC-specific outcomes, including CRC-specific survival
      and time to recurrence, did not differ significantly between men and women (HR =
      1.15, 95% CI, 0.91-1.45; and HR = 1.12, 95% CI, 0.90-1.40, respectively).
      CONCLUSION: Women diagnosed with early stage CRC lived longer and had better
      general health than men. When noncancer causes of death were excluded, however,
      the trajectory of CRC appeared similar irrespective of sex. Early identification
      and better management of comorbidities may narrow the survival gap between men
      and women.

PMID- 30120077
TI  - Evaluation of in vitro antioxidant, antiglycation and antimicrobial potential of
      indigenous Myanmar medicinal plants.
AB  - OBJECTIVE: Myanmar has a long history of using medicinal plants for treatment of
      various diseases. To the best of our knowledge there are no previous reports on
      antiglycation activities of medicinal plants from Myanmar. Therefore, this study
      was aimed to evaluate the antioxidant, antiglycation and antimicrobial properties
      of 20 ethanolic extracts from 17 medicinal plants indigenous to Myanmar. METHODS:
      In vitro scavenging assays of 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide
      (NO), superoxide (SO) radicals were used to determine the antioxidant activities.
      Folin-Ciocalteu's method was performed to determine the total phenolic content.
      Antiglycation and antimicrobial activities were detected by bovine serum albumin
      fluorescent assay and agar well diffusion method. RESULTS: Terminalia chebula
      Retz. (Fruit), containing the highest total phenolic content, showed high
      antioxidant activities with inhibition of 77.98% +/- 0.92%, 88.95% +/- 2.42%,
      88.56% +/- 1.87% and 70.74%+/- 2.57% for DPPH, NO, SO assays and antiglycation
      activity respectively. It also showed the antimicrobial activities against
      Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa
      and Candida albicans with inhibition zone of 19, 18, 17, 25 and 15 mm,
      respectively. Garcinia mangostana Linn. showed the strongest activities for SO
      and antiglycation assays with inhibition of 93.68% +/- 2.63% and 82.37% +/-
      1.78%. Bark of Melia sp. was the best NO radical scavenger with inhibition rate
      of 89.39%+/- 0.60%. CONCLUSION: The results suggest that these plants are
      potential sources of antioxidants with free radical-scavenging and antiglycation
      activities and could be useful for decreasing the oxidative stress and glycation
      end-product formation in glycation-related diseases.

PMID- 30120078
TI  - Antimicrobial activity of Cannabis sativa, Thuja orientalis and Psidium guajava
      leaf extracts against methicillin-resistant Staphylococcus aureus.
AB  - OBJECTIVE: This study examined the antimicrobial activity of Cannabis sativa,
      Thuja orientalis and Psidium guajava against methicillin-resistant Staphylococcus
      aureus (MRSA) and used a standardized purification protocol to determine the
      presence and abundance of bioactive compounds in the leaf extracts. METHODS: In
      vitro antimicrobial activities of the ethanolic extracts of C. sativa, T.
      orientalis and P. guajava were tested against MRSA. The presence of bioactive
      molecules in these three leaves was evaluated using biochemical assays and high
      performance thin-layer chromatography (HPTLC). RESULTS: Resistance to
      methicillin, penicillin, oxacillin and cefoxitin was observed in each of the
      clinical and nonclinical MRSA isolates. However, they were still vulnerable to
      vancomycin. Used individually, the 50% extract of each plant leaf inhibited MRSA
      growth. A profound synergism was observed when C. sativa was used in combination
      with T. orientalis (1:1) and when P. guajava was used in combination with T.
      orientalis (1:1). This was shown by larger zones of inhibition. This synergism
      was probably due to the combined inhibitory effect of phenolics present in the
      leaf extracts (i.e., quercetin and gallic acid) and catechin, as detected by
      HPTLC. CONCLUSION: The leaf extracts of C. sativa, T. orientalis and P. guajava
      had potential for the control of both hospital- and community-acquired MRSA.
      Moreover, the inhibitory effect was enhanced when extracts were used in
      combination.

PMID- 30120079
TI  - Revisiting IL-13 blockade: can we reach the wonderland the inhaled way?

PMID- 30120080
TI  - Recapitulation of hepatitis B virus-host interactions in liver organoids from
      human induced pluripotent stem cells.
AB  - Therapies against hepatitis B virus (HBV) have improved in recent decades;
      however, the development of individualized treatments has been limited by the
      lack of individualized infection models. In this study, we used human induced
      pluripotent stem cell (hiPSC) to generate a functional liver organoid (LO) that
      inherited the genetic background of the donor, and evaluated its application in
      modeling HBV infection and exploring virus-host interactions. To establish a
      functional hiPSC-LO, we cultured hiPSC-derived endodermal, mesenchymal, and
      endothelial cells with a chemically defined medium in a three-dimensional
      microwell culture system. Based on cell-cell interactions, these cells could
      organize themselves and gradually differentiate into a functional organoid, which
      exhibited stronger hepatic functions than hiPSC derived hepatic like cell (HLC).
      Moreover, the functional LO demonstrated more susceptibility to HBV infection
      than hiPSC-HLC, and could maintain HBV propagation and produce infectious virus
      for a prolonged duration. Furthermore, we found that virus infection could cause
      hepatic dysfunction of hiPSC-LOs, with down-regulation of hepatic gene
      expression, induced release of early acute liver failure markers, and altered
      hepatic ultrastructure. Therefore, our study demonstrated that HBV infection in
      hiPSC-LOs could recapitulate virus life cycle and virus induced hepatic
      dysfunction, suggesting that hiPSC-LOs may provide a promising individualized
      infection model for the development of individualized treatment for hepatitis.

PMID- 30120081
TI  - Bile acid metabolites in early pregnancy and risk of gestational diabetes in
      Chinese women: A nested case-control study.
AB  - BACKGROUND: Bile acid metabolism plays an important role in metabolism but it is
      uncertain whether bile acid metabolites in early pregnancy are associated with
      risk of gestational diabetes mellitus (GDM). METHODS: We organized a 1:1 case
      control study nested in a prospective cohort of 22,302 pregnant women recruited
      from 2010 to 2012 in China: 243 women with GDM were matched with 243 non-GDM
      controls on age (+/-1 year). Conditional logistic regression and restricted cubic
      spline were used to examine full-range associations of bile acid metabolites with
      GDM. FINDINGS: All the 9 detectable bile acids were inversely associated with the
      risk of GDM, among them, 8 in nonlinear and one in largely linear manners in
      multivariable analysis. Glycoursodeoxycholic acid (GUDCA) at <=0.07 nmol/mL and
      deoxycholic acid (DCA) at <=0.28 nmol/mL had threshold effects and their
      decreasing levels below the cutoff points were associated with rapid rises in the
      risk of GDM. In traditional risk factor model, the stepwise procedure identified
      that GUDCA <= 0.07 nmol/mL and DCA <= 0.280 nmol/mL were still significant (OR:
      6.84, 95%CI: 1.10-42.48 & 2.06, 1.26-3.37), while other bile acids were not.
      Inclusion of the two bile acids in the model increased the area under operating
      characteristic's curve from 0.69 to 0.76 (95% CI: 0.71-0.80) (P < .05).
      INTERPRETATION: Serum GUDCA <= 0.07 nmol/mL and DCA <= 0.28 nmol/mL in early
      pregnancy were independently associated with increased risk of GDM in Chinese
      pregnant women. FUNDING: Talent Recruitment Scheme grant of Tianjin Medical
      University and National Key Research and Development Program, etc.

PMID- 30120082
TI  - Tissue-specific effects of targeted mutation of Mir29b1 in rats.
AB  - BACKGROUND: miR-29 is a master regulator of extracellular matrix genes, but
      conflicting data on its anti-fibrotic effect have been reported. miR-29 improves
      nitric oxide (NO) production in arterioles by targeting Lypla1. Mir29b1 targeted
      mutation exacerbates hypertension in a model derived from the Dahl salt-sensitive
      rat. We examined the effect of Mir29b1 mutation on tissue fibrosis and NO levels
      with a focus on kidney regions. METHODS: Mir29b1 targeted mutant rats on the
      genetic background of SS-Chr13BN rats were studied. Masson trichrome staining,
      molecular and biochemical assays, metabolic cage studies, and bioinformatic
      analysis of human genomic data were performed. FINDINGS: The abundance of miR-29b
      and the co-transcribed miR-29a was substantially lower in mutant rats. Tissue
      fibrosis was significantly increased in the renal outer medulla, but not in the
      renal cortex, heart or liver in mutant rats on a 0.4% NaCl diet. Lypla1 protein
      abundance was significantly higher and NO levels lower in the renal outer
      medulla, but not in the renal cortex. After 14 days of a 4% NaCl diet, 24 h urine
      volume and urinary sodium excretion was significantly lower in mutant rats, and
      tissue fibrosis became higher in the heart. NO levels were lower in the renal
      outer medulla and heart, but not in the renal cortex. Human miR-29 genes are
      located in proximity with blood pressure-associated single nucleotide
      polymorphisms. INTERPRETATION: The renal outer medulla might be particularly
      susceptible to the injurious effects of a miR-29 insufficiency, which might
      contribute to the development of hypertension in Mir29b1 mutant rats.

PMID- 30120088
TI  - Most GP trainees intend to work less than full time, survey shows.

PMID- 30120086
TI  - Adoption of Stroke Rehabilitation Technologies by the User Community: Qualitative
      Study.
AB  - BACKGROUND: Using technology in stroke rehabilitation is attractive. Devices such
      as robots or smartphones can help deliver evidence-based levels of practice
      intensity and automated feedback without additional labor costs. Currently,
      however, few technologies have been adopted into everyday rehabilitation.
      OBJECTIVE: This project aimed to identify stakeholder (therapists, patients, and
      caregivers) priorities for stroke rehabilitation technologies and to generate
      user-centered solutions for enhancing everyday adoption. METHODS: We invited
      stakeholders (n=60), comprising stroke survivors (20/60, 33%), therapists (20/60,
      33%), caregivers, and technology developers (including researchers; 20/60, 33%),
      to attend 2 facilitated workshops. Workshop 1 was preceded by a national survey
      of stroke survivors and therapists (n=177) to generate an initial list of
      priorities. The subsequent workshop focused on identifying practical solutions to
      enhance adoption. RESULTS: A total of 25 priorities were generated from the
      survey; these were reduced to 10 nonranked priorities through discussion,
      consensus activities, and voting at Workshop 1: access to technologies, ease of
      use, awareness of available technologies, technologies focused on function,
      supports self-management, user training, evidence of effectiveness, value for
      money, knowledgeable staff, and performance feedback. The second workshop
      provided recommendations for improving the adoption of technologies in stroke
      rehabilitation: an annual exhibition of commercially available and developing
      technologies, an online consumer-rating website of available technologies, and a
      user network to inspire and test new technologies. CONCLUSIONS: The key outcomes
      from this series of stakeholder workshops provides a starting point for an
      integrated approach to promoting greater adoption of technologies in stroke
      rehabilitation. Bringing technology developers and users together to shape future
      and evaluate current technologies is critical to achieving evidence-based stroke
      rehabilitation.

PMID- 30120085
TI  - A Mobile App (WhiteTeeth) to Promote Good Oral Health Behavior Among Dutch
      Adolescents with Fixed Orthodontic Appliances: Intervention Mapping Approach.
AB  - BACKGROUND: The insertion of fixed orthodontic appliances increases the risk of
      dental caries, particularly in adolescents. Caries can be prevented through good
      oral health behavior. To support adolescents with fixed orthodontic appliances
      and for promoting oral health behavior, we developed a theory- and evidence-based
      mHealth program, the WhiteTeeth app. OBJECTIVE: The objective of our paper was to
      describe the systematic development and content of the WhiteTeeth app. METHODS:
      For systematic development of the program, we used the intervention mapping (IM)
      approach. In this paper, we present the results of applying the first 5 steps of
      IM to the design of an mHealth program: (1) identifying target behaviors and
      determinants through problem analysis, including a literature search, a survey
      study, and semistructured interviews, to explore adolescent oral health behavior
      during orthodontic therapy; (2) defining program outcomes and objectives; (3)
      selecting theoretical methods and translating them into practical strategies for
      the program design; (4) producing the program, including a pilot test with 28
      adolescents testing the acceptability and usability of the WhiteTeeth app; and
      (5) planning implementation and adoption. RESULTS: On the basis of our literature
      search, we identified fluoride use and control of dental plaque levels (eg, tooth
      brushing and proxy brush usage) as target behaviors for preventing caries. Next,
      we identified important and changeable determinants of oral health behavior that
      fitted the theoretical concepts of the Health Action Process Approach (HAPA)
      theory. The HAPA theory, the self-regulation theory, and the results of the
      semistructured interviews were used to define the program objectives, that is,
      the performance and change objectives. After defining the objectives, we
      identified multiple behavior change techniques that could be used to achieve
      these objectives, such as providing oral health information and feedback,
      prompting self-monitoring, coaching of set actions and coping plans, and sending
      reminders. We translated these methods into practical strategies, such as videos
      and a brushing timer. Next, we combined these strategies into a single program
      resulting in the WhiteTeeth app (which is available on both iTunes and Google
      Play stores as "Witgebit"). Adolescents with fixed orthodontic appliances and
      dental professionals were included in the development process to increase the
      success of implementation. The pilot test revealed that the app users appreciated
      and liked the app. The WhiteTeeth app can be integrated into current orthodontic
      care. CONCLUSIONS: IM allowed us to identify multiple techniques that have been
      shown to be the most effective in initiating behavior change, but have not yet
      been incorporated into existing orthodontic apps. The WhiteTeeth app contains all
      these techniques, which makes it a unique and promising home-based app for
      promoting oral health in adolescents with fixed orthodontic appliances.

PMID- 30120083
TI  - Genome-Wide Association Study of Circadian Rhythmicity in 71,500 UK Biobank
      Participants and Polygenic Association with Mood Instability.
AB  - BACKGROUND: Circadian rhythms are fundamental to health and are particularly
      important for mental wellbeing. Disrupted rhythms of rest and activity are
      recognised as risk factors for major depressive disorder and bipolar disorder.
      METHODS: We conducted a genome-wide association study (GWAS) of low relative
      amplitude (RA), an objective measure of rest-activity cycles derived from the
      accelerometer data of 71,500 UK Biobank participants. Polygenic risk scores (PRS)
      for low RA were used to investigate potential associations with psychiatric
      phenotypes. OUTCOMES: Two independent genetic loci were associated with low RA,
      within genomic regions for Neurofascin (NFASC) and Solute Carrier Family 25
      Member 17 (SLC25A17). A secondary GWAS of RA as a continuous measure identified a
      locus within Meis Homeobox 1 (MEIS1). There were no significant genetic
      correlations between low RA and any of the psychiatric phenotypes assessed.
      However, PRS for low RA was significantly associated with mood instability across
      multiple PRS thresholds (at PRS threshold 0.05: OR = 1.02, 95% CI = 1.01-1.02, p
      = 9.6 * 10-5), and with major depressive disorder (at PRS threshold 0.1: OR =
      1.03, 95% CI = 1.01-1.05, p = 0.025) and neuroticism (at PRS threshold 0.5: Beta
      = 0.02, 95% CI = 0.007-0.04, p = 0.021). INTERPRETATION: Overall, our findings
      contribute new knowledge on the complex genetic architecture of circadian
      rhythmicity and suggest a putative biological link between disrupted circadian
      function and mood disorder phenotypes, particularly mood instability, but also
      major depressive disorder and neuroticism. FUNDING: Medical Research Council
      (MR/K501335/1).

PMID- 30120084
TI  - Internet-Based Universal Prevention for Students and Parents to Prevent Alcohol
      and Cannabis Use Among Adolescents: Protocol for the Randomized Controlled Trial
      of Climate Schools Plus.
AB  - BACKGROUND: Early initiation of alcohol and cannabis use markedly increases the
      risk of harms associated with use, including the development of substance use and
      mental health disorders. To interrupt this trajectory, effective prevention
      during the adolescent period is critical. Despite evidence showing that parents
      can play a critical role in delaying substance use initiation, the majority of
      prevention programs focus on adolescents only. Accordingly, the Climate Schools
      Plus (CSP) program was developed to address this gap. OBJECTIVE: This paper
      outlines the protocol for a cluster randomized controlled trial (RCT) of the CSP
      program, a novel internet-based program for parents and students to prevent
      adolescent substance use and related harms. The CSP program builds on the success
      of the Climate Schools student programs, with the addition of a newly developed
      parenting component, which allows parents to access the internet-based content to
      equip them with knowledge and skills to help prevent substance use in their
      adolescents. METHODS: A cluster RCT is being conducted with year 8 students (aged
      12-14 years) and their parents from 12 Australian secondary schools between 2018
      and 2020. Using blocked randomization, schools are assigned to one of the two
      groups to receive either the CSP program (intervention) or health education as
      usual (control). The primary outcomes of the trial will be any student alcohol
      use (>=1 standard alcoholic drink/s) and any student drinking to excess (>=5
      standard alcoholic drinks). Secondary outcomes will include alcohol- and cannabis
      related knowledge, alcohol use-related harms, frequency of alcohol consumption,
      frequency of drinking to excess, student cannabis use, parents' self-efficacy to
      stop their children using alcohol, parental supply of alcohol, and parent
      adolescent communication. All students and their parents will complete
      assessments on three occasions-baseline and 12 and 24 months postbaseline. In
      addition, students and parents in the intervention group will be asked to
      complete program evaluations on two occasions-immediately following the year 8
      program and immediately following the year 9 program. RESULTS: Analyses will be
      conducted using multilevel, mixed-effects models within an intention-to-treat
      framework. It is expected that students in the intervention group will have less
      uptake and excessive use of alcohol compared with the students in the control
      group. CONCLUSIONS: This study will provide the first evaluation of a combined
      internet-based program for students and their parents to prevent alcohol and
      cannabis use. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry
      ACTRN12618000153213;
      https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374178 (Archived
      by WebCite at http://www.webcitation.org/71E0prqfQ). REGISTERED REPORT
      IDENTIFIER: RR1-10.2196/10849.

PMID- 30120087
TI  - Relationship Between Internet Health Information and Patient Compliance Based on
      Trust: Empirical Study.
AB  - BACKGROUND: The internet has become a major mean for acquiring health
      information; however, Web-based health information is of mixed quality and may
      markedly affect patients' health-related behavior and decisions. According to the
      social information processing theory, patients' trust in their physicians may
      potentially change due to patients' health-information-seeking behavior.
      Therefore, it is important to identify the relationship between internet health
      information and patient compliance from the perspective of trust. OBJECTIVE: The
      objective of our study was to investigate the effects of the quality and source
      of internet health information on patient compliance using an empirical study
      based on the social information processing theory and social exchange theory.
      METHODS: A Web-based survey involving 336 valid participants was conducted in
      China. The study included independent variables (internet health information
      quality and source of information), 2 mediators (cognition-based trust [CBT] and
      affect-based trust [ABT]), 1 dependent variable (patient compliance), and 3
      control variables (gender, age, and job). All variables were measured using
      multiple-item scales from previously validated instruments, and confirmative
      factor analysis as well as structural equation modeling was used to test
      hypotheses. RESULTS: The questionnaire response rate was 77.16% (375/486),
      validity rate was 89.6% (336/375), and reliability and validity were acceptable.
      We found that the quality and source of internet health information affect
      patient compliance through the mediation of CBT and ABT. In addition, internet
      health information quality has a stronger influence on patient compliance than
      the source of information. However, CBT does not have any direct effect on
      patient compliance, but it directly affects ABT and then indirectly impacts
      patient compliance. Therefore, the effect of ABT seems stronger than that of CBT.
      We found an unexpected, nonsignificant relationship between the source of
      internet health information and ABT. CONCLUSIONS: From patients' perspective,
      internet health information quality plays a stronger role than its source in
      impacting their trust in physicians and the consequent compliance with
      physicians. Therefore, patient compliance can be improved by strengthening the
      management of internet health information quality. The study findings also
      suggest that physicians should focus on obtaining health information from health
      websites, thereby expanding their understanding of patients' Web-based health
      information-seeking preferences, and enriching their knowledge structure to show
      their specialization and reliability in the communication with patients. In
      addition, the mutual demonstration of care and respect in the communication
      between physicians and patients is important in promoting patients' ABT in their
      physicians.

PMID- 30120089
TI  - Oral steroids fail to prevent hearing loss in children with otitis media with
      effusion, shows trial.

PMID- 30120090
TI  - Commentary: does the selective inversion approach demonstrate bias in the results
      of studies using routinely collected data?

PMID- 30120092
TI  - Mueller S, Meinecke A-K, Buchwald S, Eriksson D, Wilke T. Does treatment
      satisfaction influence adherence to treatment?: impact of AF patients' treatment
      satisfaction on adherence to oral anticoagulation treatment [abstract]. Blood.
      2017;130(suppl 1). Abstract 2142.

PMID- 30120093
TI  - What readers thought about a research paper's approach to compare treatment
      effects on mortality.

PMID- 30120091
TI  - Mueller S, Meinecke A-K, Buchwald S, Eriksson D, Wilke T. Real-world adherence to
      non-vitamin K antagonist oral anticoagulants in patients with atrial
      fibrillation: results of an international survey [abstract]. Blood.
      2017;130(suppl 1). Abstract 4726.

PMID- 30120094
TI  - Brazil's child and maternal mortality have increased against background of public
      spending cuts.

PMID- 30120095
TI  - Response to 'Response to viewpoint 'Defining refractory rheumatoid arthritis' by
      Buch' by Roodenrijs et al.

PMID- 30120097
TI  - Focusing on overdiagnosis as a driver of too much medicine.

PMID- 30120096
TI  - Cleaved N-terminal histone tails distinguish between NADPH oxidase (NOX)
      dependent and NOX-independent pathways of neutrophil extracellular trap
      formation.
AB  - OBJECTIVES: Neutrophil extracellular traps (NETs) act in various rheumatic
      diseases. Although NET formation was originally described as a nicotinamide
      adenine dinucleotide phosphate (NADPH) oxidase (NOX)-dependent pathway, it
      appears that there are also NOX-independent pathways of NET release. Currently,
      no tools are available that can discriminate between both NET-forming pathways.
      We aimed to develop a serological method allowing the discrimination between NETs
      generated through NOX-dependent or NOX-independent pathways. METHODS: Histones
      from in vitro generated NOX-dependent and NOX-independent NETs were characterised
      with a panel of lupus-derived antibodies against N-terminal histone tails using
      immunofluorescence microscopy, western blot and ELISA. NETs in patients with NET
      associated diseases, that is, rheumatoid arthritis (RA), systemic lupus
      erythematosus (SLE), psoriatic arthritis (PsA) and sepsis, were characterised in
      sandwich ELISAs employing antibodies against myeloperoxidase (MPO) and N-terminal
      histone tails as detecting and capturing antibodies, respectively. Functional
      responses of endothelial cells to NOX-dependent and NOX-independent NETs were
      assessed as well. RESULTS: Neutrophil elastase cleaves the N-terminal tails of
      core histones during NOX-dependent, but not during NOX-independent NET formation.
      Consequently, the detection of MPO-histone complexes with antibodies against N
      terminal histone tails allows discrimination between NETs formed through a NOX
      dependent or NOX-independent manner. Characterisation of in vivo circulating NETs
      revealed the presence of NOX-independent NETs in RA, SLE and sepsis, but NOX
      dependent NETs in PsA. NOX-independent NETs displayed an increased capacity to
      activate endothelial cells when compared with NOX-dependent NETs. CONCLUSIONS:
      These results indicate heterogeneity in NET-forming pathways in vivo and
      highlight the need for disease-specific strategies to prevent NET-mediated
      pathology.

PMID- 30120098
TI  - Doctors are given go ahead to extract sperm from unconscious man in legal first.

PMID- 30120099
TI  - E-cigarettes: relax rules to help more smokers quit, say MPs.

PMID- 30120101
TI  - A Healthy Life for a Child With Medical Complexity: 10 Domains for
      Conceptualizing Health.
AB  - BACKGROUND AND OBJECTIVES: Defining and measuring health for children with
      medical complexity (CMC) is poorly understood. We engaged a diverse national
      sample of stakeholder experts to generate and then synthesize a comprehensive
      list of health outcomes for CMC. METHODS: With national snowball sampling of CMC
      caregiver, advocate, provider, researcher, and policy or health systems experts,
      we identified 182 invitees for group concept mapping (GCM), a rigorous mixed
      methods approach. Respondents (n = 125) first completed Internet-based idea
      generation by providing unlimited short, free-text responses to the focus prompt,
      "A healthy life for a child or youth with medical complexity includes: ___." The
      resulting 707 statements were reduced to 77 unique ideas. Participants sorted the
      ideas into clusters based on conceptual similarity and rated items on perceived
      importance and measurement feasibility. Responses were analyzed and mapped via
      GCM software. RESULTS: The cluster map best fitting the data had 10 outcome
      domains: (1) basic needs, (2) inclusive education, (3) child social integration,
      (4) current child health-related quality of life, (5) long-term child and family
      self-sufficiency, (6) family social integration, (7) community system supports,
      (8) health care system supports, (9) a high-quality patient-centered medical
      home, and (10) family-centered care. Seventeen outcomes representing 8 of the 10
      domains were rated as both important and feasible to measure ("go zone").
      CONCLUSIONS: GCM identified a rich set of CMC outcome domains. Go-zone items
      provide an opportunity to test and implement measures that align with a broad
      view of health for CMC and potentially all children.

PMID- 30120102
TI  - The Future of Measuring Health Outcomes for Children With Medical Complexity.

PMID- 30120100
TI  - Aspirin enhances the sensitivity of hepatocellular carcinoma side population
      cells to doxorubicin via miR-491/ABCG2.
AB  - Objective: To explore whether aspirin (ASA) enhances the sensitivity of
      hepatocellular carcinoma (HCC) side population (SP) cells to doxorubicin (Doxo)
      via miR-491/ATP-binding cassette sub-family G member 2 (ABCG2).Methods: Non-SP
      and SP cells were isolated from MHCC-97L cell line using flow cytometry analysis
      and fluorescence-activated cell sorting. Colony formation assay was performed to
      determine the colony-formation ability of cells. Cell viability of SP cells was
      determined with the MTT assay. Luciferase reporter assay was applied in
      confirming the binding between miR-491 and ABCG2.Results: Although the Doxo
      treatment lowered the colony-formation ability of both non-SP and SP cells, the
      colony-formation ability of SP cells was 2-fold higher than that of non-SP cells
      (P<0.05). Doxo slightly inhibited the cell viability of SP cells in a
      concentration-dependent manner; the addition of ASA dramatically enhanced the
      inhibitory effect of Doxo on SP cell viability in a concentration-dependent
      manner (P<0.05). Compared with non-SP cells, the miR-491 expression was
      significantly decreased in SP cells, which was significantly reversed by ASA
      (P<0.05). miR-491 directly controlled the ABCG2 expression. In the presence of
      Doxo, miR-491 inhibitor reduced the inhibitory effect of ASA on the cell
      viability of SP cells, which was significantly reversed by knockdown of ABCG2
      (P<0.05).Conclusion: ASA enhanced the sensitivity of SP cells to Doxo via
      regulating the miR-491/ABCG2 signaling pathway.

PMID- 30120103
TI  - Baseline Cytokine Profiles of Tuberculin-Specific CD4+ T Cells in Non-Muscle
      Invasive Bladder Cancer May Predict Outcomes of BCG Immunotherapy.
AB  - Intravesical Bacillus Calmette-Guerin (BCG) immunotherapy preserves the bladder
      after resection of high-risk non-muscle-invasive bladder cancer (NMIBC). About
      30% of patients experience treatment failure, which cannot be predicted a priori
      and carries a high risk of disease progression. We examined the in vitro
      tuberculin responsiveness of CD4+ T cells before BCG immunotherapy in 42 patients
      with high-risk NMIBC. The frequencies and functionalities of cytokine-expressing
      CD4+ T cells immediately before and after BCG immunotherapy induction were
      assessed by flow cytometry after overnight tuberculin stimulation. Tuberculin
      induced secreted mediators were measured by electrochemiluminescence. We
      correlated the results with recurrence-free patient survival 6 months after
      induction. A tuberculin-induced, secreted, IL2 concentration > 250 pg/mL was the
      best predictor of recurrence-free survival, providing 79% sensitivity, 86%
      specificity (AUC = 0.852, P = 0.000), and overall correct classification in 78.6%
      of cases. In 50% of patients later experiencing recurrence, but not in any of the
      recurrence-free survivors, IL2 secretion was < 120 pg/mL. Other parameters
      predicting recurrence-free survival included secreted IFNgamma (AUC = 0.796, P =
      0.002) and the frequencies of TNF-producing (TNF+) CD4+ T cells (AUC = 0.745, P =
      0.010). "Polyfunctional" CD4+ T cells (IFNgamma+/IL2+/TNF+) were significantly
      associated with recurrence-free survival (AUC = 0.801, P = 0.002). Thus, the
      amount of IL2 secretion from CD4+ T cells after overnight in vitro incubation
      with tuberculin predicted the outcome of BCG immunotherapy. As many as half of
      potential BCG failures could be identified before induction therapy is begun,
      enabling better choices regarding treatment. Cancer Immunol Res; 6(10); 1212-9.
      (c)2018 AACR.

PMID- 30120105
TI  - TREM-like transcript 1: a more sensitive marker of platelet activation than P
      selectin in humans and mice.

PMID- 30120104
TI  - Evaluation of induction chemotherapies after hypomethylating agent failure in
      myelodysplastic syndromes and acute myeloid leukemia.
AB  - Hypomethylating agent (HMA) failure in acute myeloid leukemia (AML) and
      myelodysplastic syndromes (MDS) carries a poor prognosis with limited treatment
      options. Although intensive, remission induction chemotherapy is often used
      subsequently, in particular to bridge to allogeneic transplantation, it is not
      clear whether an advantage exists for any particular regimen. Based on an
      international collaboration, we retrospectively analyzed induction response rate
      and survival in 366 patients after HMA failure. Patients received 7+3,
      intermediate- to high-dose cytarabine (IDAC), or purine nucleoside analog-based
      regimens. For the MDS cohort (n = 307), the overall response rate (ORR) was 41%;
      median overall survival (OS) was 10.8 months, and 40% of responding patients
      bridged to allogeneic stem cell transplant (allo-SCT). For the AML cohort (n =
      59), the ORR was 32%, OS 6 months, and 42% of responding patients bridged to allo
      SCT. Prognostic factors for response in MDS included adverse cytogenetics (odds
      ratio [OR], 0.46, P = .01), age >=65 years (OR, 0.47; P < .01), and use of IDAC
      (OR, 2.91, P = .01). Shorter survival was associated with adverse cytogenetics
      (hazard ratio [HR], 1.43; P = .06). In the AML cohort, OS was decreased by
      disease progression at time of HMA failure (HR, 2.66; P = .02) and prolonged with
      use of an anthracycline-containing regimen (HR, 0.37; P = .01). In conclusion,
      intensive chemotherapy after HMA failure may be a reasonable treatment option for
      selected patients as a bridge to allogeneic transplantation and should be
      considered a potential platform for future investigations.

PMID- 30120106
TI  - Isoproterenol-induced beta-2 adrenergic receptor activation negatively regulates
      interleukin-2 signaling.
AB  - Regulation of intracellular signaling pathways in lymphocytes is critical for
      cell homeostasis and immune response. Interleukin-2 (IL-2), a key regulator of
      lymphocytes, signals following receptor-ligand engagement and subsequent
      recruitment and activation of effector proteins including JAKs and STATs.
      Lymphocytes can also be regulated by the central nervous system through the beta2
      adrenergic receptor (beta2AR) pathway which can affect cell trafficking,
      proliferation, differentiation, and cytokine production. The cross-talk between
      these two signaling pathways represents an important mechanism that has yet to be
      fully elucidated. The present study provides evidence for communication between
      the IL-2 receptor (IL-2R) and beta2AR. Treatment of human lymphoid cell lines
      with the beta2AR agonist isoproterenol (ISO) alone increased cAMP levels and
      mediated a stimulatory response by activating AKT and ERK to promote cell
      viability. Interestingly, ISO activation of beta2AR also induced threonine
      phosphorylation of the IL-2Rbeta. In contrast, ISO treatment prior to IL-2
      stimulation produced an inhibitory signal that disrupted IL-2 induced activation
      of the JAK/STAT, MEK/ERK, and PI3K pathways by inhibiting the formation of the IL
      2R beta-gamma chain complex, and subsequently cell proliferation. Moreover,
      gammac-family cytokines-mediated STAT5 activation was also inhibited by ISO.
      These results suggest a molecular mechanism by which beta2AR signaling can both
      stimulate and suppress lymphocyte responses and thus explain how certain
      therapeutic agents, such as vasodilators, may impact immune responsiveness.

PMID- 30120109
TI  - MUC1 Makes Me Miserable.

PMID- 30120107
TI  - IFN-gamma-response mediator GBP-1 represses human cell proliferation by
      inhibiting the Hippo signaling transcription factor TEAD.
AB  - Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that exerts important
      functions in inflammation, infectious diseases, and cancer. The large GTPase
      human guanylate-binding protein 1 (GBP-1) is among the most strongly IFN-gamma
      induced cellular proteins. Previously, it has been shown that GBP-1 mediates
      manifold cellular responses to IFN-gamma including the inhibition of
      proliferation, spreading, migration, and invasion and through this exerts anti
      tumorigenic activity. However, the mechanisms of GBP-1 anti-tumorigenic
      activities remain poorly understood. Here, we elucidated the molecular mechanism
      of the human GBP-1-mediated suppression of proliferation by demonstrating for the
      first time a cross-talk between the anti-tumorigenic IFN-gamma and Hippo
      pathways. The alpha9-helix of GBP-1 was found to be sufficient to inhibit
      proliferation. Protein-binding and molecular modeling studies revealed that the
      alpha9-helix binds to the DNA-binding domain of the Hippo signaling transcription
      factor TEA domain protein (TEAD) mediated by the 376VDHLFQK382 sequence at the N
      terminus of the GBP-1-alpha9-helix. Mutation of this sequence resulted in
      abrogation of both TEAD interaction and suppression of proliferation. Further on,
      the interaction caused inhibition of TEAD transcriptional activity associated
      with the down-regulation of TEAD-target genes. In agreement with these results,
      IFN-gamma treatment of the cells also impaired TEAD activity, and this effect was
      abrogated by siRNA-mediated inhibition of GBP-1 expression. Altogether, this
      demonstrated that the alpha9-helix is the proliferation inhibitory domain of GBP
      1, which acts independent of the GTPase activity through the inhibition of the
      Hippo transcription factor TEAD in mediating the anti-proliferative cell response
      to IFN-gamma.

PMID- 30120110
TI  - Dysregulated Urea Cycle-Associated Signatures Are Tumor Biomarkers.
AB  - Urea cycle dysregulation is linked to both poor prognosis and improved response
      to immunotherapy.

PMID- 30120108
TI  - Racial Disparities in Nephrology Consultation and Disease Progression among
      Veterans with CKD: An Observational Cohort Study.
AB  - BACKGROUND: Incident rates of ESRD are much higher among black and Hispanic
      patients than white patients. Access to nephrology care before progression to
      ESRD is associated with better clinical outcomes among patients with CKD.
      However, it is unknown whether black or Hispanic patients with CKD experience
      lower pre-ESRD nephrology consultation rates compared with their white
      counterparts, or whether such a disparity contributes to worse outcomes among
      minorities. METHODS: We assembled a retrospective cohort of patients with CKD who
      received care through the Veterans Health Administration from 2003 to 2015,
      focusing on individuals with incident CKD stage 4 who had an initial eGFR>=60
      ml/min per 1.73 m2 followed by two consecutive eGFRs<30 ml/min per 1.73 m2. We
      repeated analyses among individuals with incident CKD stage 3. Outcomes included
      nephrology provider referral, nephrology provider visit, progression to CKD stage
      5, and mortality. RESULTS: We identified 56,767 veterans with CKD stage 4 and
      640,704 with CKD stage 3. In both cohorts, rates of nephrology referral and
      visits were significantly higher among black and Hispanic veterans than among non
      Hispanic white veterans. Despite this, both black and Hispanic patients
      experienced faster progression to CKD stage 5 compared with white patients. Black
      patients with CKD stage 4 experienced slightly lower mortality than white
      patients, whereas black patients with CKD stage 3 had a small increased risk of
      death. CONCLUSIONS: Black or Hispanic veterans with CKD are more likely than
      white patients to see a nephrologist, yet are also more likely to suffer disease
      progression. Biologic and environmental factors may play a bigger role than
      nephrology consultation in driving racial disparities in CKD progression.

PMID- 30120111
TI  - Distinct Splicing Factor Mutations Converge on NF-kappaB Signaling.
AB  - Mutations in SF3B1 and SRSF2 common in myelodysplastic syndrome (MDS) are
      synthetic lethal.

PMID- 30120112
TI  - Radiotherapeutic OK'd for Neuroendocrine Tumors.
AB  - The FDA has approved the first drug for locally advanced or metastatic
      pheochromocytoma and paraganglioma-a radioactive isotope of iodine called
      iobenguane I 131 that's absorbed by tumor cells. Twenty-five percent of patients
      who received it reduced their use of antihypertensive drugs by half for at least
      6 months.

PMID- 30120113
TI  - Gastric Cancer Organoids Reveal a Wnt Inhibitor Sensitive Subset.
AB  - Gastric cancers gain R-spondin independence by multiple mechanisms including
      CDH1/TP53 comutations.

PMID- 30120114
TI  - The Nucleoporin POM121 Enhances Prostate Cancer Aggressiveness.
AB  - POM121 is upregulated in aggressive and lethal prostate cancers and promotes
      tumor growth in vivo.

PMID- 30120115
TI  - Single-Cell RNA Sequencing Uncovers Kidney Tumor Cells of Origin.
AB  - Wilms tumors arise from fetal cells whereas adult tumors arise from proximal
      convoluted tubular cells.

PMID- 30120116
TI  - Methods for Handling Left-Censored Data in Quantitative Microbial Risk
      Assessment.
AB  - Data below detection limits, left-censored data, are common in environmental
      microbiology, and decisions in handling censored data may have implications for
      quantitative microbial risk assessment (QMRA). In this paper, we utilize
      simulated data sets informed by real-world enterovirus water data to evaluate
      methods for handling left-censored data. Data sets were simulated with four
      censoring degrees (low (10%), medium (35%), high (65%), and severe (90%)) and one
      real life censoring example (97%) and were informed by enterovirus data assuming
      a lognormal distribution with a 2.3 genome copies/L limit of detection (LOD). For
      each data set, 5 methods for handling left-censored data were applied: 1)
      Substitution with LOD/?2, 2) Lognormal maximum likelihood estimation (MLE) to
      estimate mean and standard deviation, 3) Kaplan-Meier estimates (KM), 4)
      Imputation method using MLE to estimate distribution parameters (MI Method 1), 5)
      Imputing from a uniform distribution (MI Method 2). Each data set mean was used
      to estimate enterovirus dose and infection risk. Root mean square error (RMSE)
      and bias were used to compare estimated and known doses and infection risks. MI
      Method 1 resulted in lowest dose and infection risk RMSE and bias ranges for most
      censoring degrees, predicting infection risks at most 1.17 x 10-2 from known
      values under 97% censoring. MI Method 2 was the next overall best method. For
      medium to severe censoring, MI Method 1 may result in the least error. If unsure
      of the distribution, MI Method 2 may be a preferred method to avoid distribution
      misspecification.IMPORTANCEThis study evaluates methods for handling low (10%) to
      severe (90%) left-censored data within an environmental microbiology context, and
      demonstrates that some of these methods may be appropriate when using data
      containing concentrations below a limit of detection to estimate infection risks.
      Additionally, this study uses a skewed data set, which is an issue typically
      faced by environmental microbiologists.

PMID- 30120117
TI  - Cyanophycin synthesis optimizes nitrogen utilization in the unicellular
      cyanobacterium Synechocystis sp. PCC 6803.
AB  - Cyanophycin is a carbon/nitrogen storage polymer widely distributed in most
      cyanobacterial strains and in a few heterotrophic bacteria. It is a non-ribosomal
      polypeptide consisting of equimolar amounts of aspartate and arginine. Here, we
      focused on the physiological function and cell biology of cyanophycin in the
      unicellular non-diazotrophic cyanobacterium Synechocystis sp. PCC 6803. To study
      the cellular localization of the cyanophycin-synthesizing enzyme CphA during
      cyanophycin synthesis and degradation, we fused it to green fluorescent protein.
      When CphA was inactive, it localized diffusely in the cytoplasm. When cyanophycin
      synthesis was triggered, CphA first aggregated into foci and later localized on
      the surface of cyanophycin granules. In corresponding cell extracts, localization
      of CphA on the cyanophycin granule surface required Mg2+ During cyanophycin
      degradation, CphA dissociated from the granule surface and returned to its
      inactive form in the cytoplasm. To investigate the physiological role of
      cyanophycin, we compared wild-type cells with a CphA-deficient mutant. Under
      standard laboratory conditions, the ability to synthesize cyanophycin did not
      confer a growth advantage. To mimic the situation in natural habitats, cells were
      cultured with fluctuating and limiting nitrogen supplementation and/or day/night
      cycles. Under all of these conditions, cyanophycin provided a fitness advantage
      to the wild-type over the mutant lacking cyanophycin. During resuscitation from
      nitrogen starvation, wild-type cells accumulated cyanophycin during the night and
      used it as an internal nitrogen source during the day. This demonstrates that
      cyanophycin can be used as a temporary nitrogen storage to uncouple nitrogen
      assimilation from photosynthesis.ImportanceWe clarified the elusive biological
      function of cyanophycin in the non-diazotrophic cyanobacterium Synechocystis sp.
      PCC 6803. Cyanophycin is a dynamic carbon/nitrogen storage polymer (multi-arginyl
      l-poly-aspartate) that is conditionally present in most cyanobacteria and a few
      heterotrophic bacteria as cellular inclusion granules. Here we show that the
      cyanophycin-synthesizing enzyme CphA in the non-active state localizes diffusely
      in the cytoplasm. When cyanophycin synthesis is triggered, active CphA first
      aggregates into foci and then covers the surface of mature cyanophycin granules,
      which in vitro requires Mg2+ as a cofactor. Cyanophycin accumulation enables
      Synechocystis sp. to optimize nitrogen assimilation under nitrogen-poor
      conditions, in particular when the nitrogen supply fluctuates and during
      day/night cycles, by allowing continuous nitrogen assimilation and storage.
      Therefore, cyanophycin provides the wild-type cyanobacterium a clear fitness
      advantage over non-cyanophycin-producing cells in natural environments with
      fluctuating nitrogen supply.

PMID- 30120118
TI  - DdvK, a Novel Major Facilitator Superfamily Transporter Essential for 5,5'
      Dehydrodivanillate Uptake by Sphingobium sp. Strain SYK-6.
AB  - The microbial conversion of lignin-derived aromatics is a promising strategy for
      the industrial utilization of this large biomass resource. However, efficient
      application requires an elucidation of the relevant transport and catabolic
      pathways. In Sphingobium sp. strain SYK-6, most of the enzyme genes involved in
      5,5'-dehydrodivanillate (DDVA) catabolism have been characterized, but the
      transporter has not yet been identified. Here, we identified SLG_07710 (ddvK) and
      SLG_07780 (ddvR), genes encoding a putative major facilitator superfamily (MFS)
      transporter and MarR-type transcriptional regulator, respectively. A ddvK mutant
      of SYK-6 completely lost the capacity to grow on and convert DDVA. DdvR repressed
      the expression of the DDVA O-demethylase oxygenase component gene (ligXa), while
      DDVA acted as the gene inducer. A DDVA uptake assay was developed by employing
      this DdvR-controlled ligXa transcriptional regulatory system. A Sphingobium
      japonicum UT26S transformant expressing ddvK acquired DDVA uptake capacity,
      indicating that ddvK encodes the DDVA transporter. DdvK, probably requiring the
      proton motive force, was suggested to be a novel MFS transporter on the basis of
      the amino acid sequence similarity. Subsequently, we evaluated the effects of
      ddvK overexpression on the production of the DDVA metabolite 2-pyrone-4,6
      dicarboxylate (PDC), a building block of functional polymers. A SYK-6 mutant of
      the PDC hydrolase gene (ligI) cultured in DDVA accumulated PDC via 5
      carboxyvanillate and grew by utilizing 4-carboxy-2-hydroxypenta-2,4-dienoate. The
      introduction of a ddvK-expression plasmid into a ligI mutant increased the growth
      rate in DDVA and the amounts of DDVA converted and PDC produced after 48 h by
      1.35- and 1.34-fold, respectively. These results indicate that enhanced
      transporter gene expression can improve metabolite production from lignin
      derivatives.IMPORTANCE The bioengineering of bacteria to selectively transport
      and metabolize natural substrates into specific metabolites is a valuable
      strategy for industrial-scale chemical production. The uptake of many substrates
      into cells requires specific transport systems, and so the identification and
      characterization of transporter genes are essential for industrial applications.
      A number of bacterial major facilitator superfamily transporters of aromatic
      acids have been identified and characterized, but many transporters of lignin
      derived aromatic acids remain unidentified. The efficient conversion of lignin,
      an abundant but unutilized aromatic biomass resource, to value-added metabolites
      using microbial catabolism requires the characterization of transporters for
      lignin-derived aromatics. In this study, we identified the transporter gene
      responsible for the uptake of 5,5'-dehydrodivanillate, a lignin-derived biphenyl
      compound, in Sphingobium sp. strain SYK-6. In addition to characterizing its
      function, we applied this transporter gene to the production of a value-added
      metabolite from 5,5'-dehydrodivanillate.

PMID- 30120120
TI  - Metabolic Capability and Phylogenetic Diversity of Mono Lake during a Bloom of
      the Eukaryotic Phototroph Picocystis sp. Strain ML.
AB  - Algal blooms in lakes are often associated with anthropogenic eutrophication;
      however, they can occur without the human introduction of nutrients to a lake. A
      rare bloom of the alga Picocystis sp. strain ML occurred in the spring of 2016 at
      Mono Lake, a hyperalkaline lake in California, which was also at the apex of a
      multiyear-long drought. These conditions presented a unique sampling opportunity
      to investigate microbiological dynamics and potential metabolic function during
      an intense natural algal bloom. We conducted a comprehensive molecular analysis
      along a depth transect near the center of the lake from the surface to a depth of
      25 m in June 2016. Across sampled depths, rRNA gene sequencing revealed that
      Picocystis-associated chloroplasts were found at 40 to 50% relative abundance,
      greater than values recorded previously. Despite high relative abundances of the
      photosynthetic oxygenic algal genus Picocystis, oxygen declined below detectable
      limits below a depth of 15 m, corresponding with an increase in microorganisms
      known to be anaerobic. In contrast to previously sampled years, both metagenomic
      and metatranscriptomic data suggested a depletion of anaerobic sulfate-reducing
      microorganisms throughout the lake's water column. Transcripts associated with
      photosystem I and II were expressed at both 2 m and 25 m, suggesting that limited
      oxygen production could occur at extremely low light levels at depth within the
      lake. Blooms of Picocystis appear to correspond with a loss of microbial activity
      such as sulfate reduction within Mono Lake, yet microorganisms may survive within
      the sediment to repopulate the lake water column as the bloom subsides.IMPORTANCE
      Mono Lake, California, provides a habitat to a unique ecological community that
      is heavily stressed due to recent human water diversions and a period of extended
      drought. To date, no baseline information exists from Mono Lake to understand how
      the microbial community responds to human-influenced drought or algal bloom or
      what metabolisms are lost in the water column as a consequence of such
      environmental pressures. While previously identified anaerobic members of the
      microbial community disappear from the water column during drought and bloom,
      sediment samples suggest that these microorganisms survive at the lake bottom or
      in the subsurface. Thus, the sediments may represent a type of seed bank that
      could restore the microbial community as a bloom subsides. Our work sheds light
      on the potential photosynthetic activity of the halotolerant alga Picocystis sp.
      strain ML and how the function and activity of the remainder of the microbial
      community responds during a bloom at Mono Lake.

PMID- 30120119
TI  - Daqu Fermentation Selects for Heat-Resistant Enterobacteriaceae and Bacilli.
AB  - Daqu is a spontaneous solid-state cereal fermentation used as saccharification
      and starter culture in Chinese vinegar and liquor production. The evolution of
      microbiota in this spontaneous fermentation is controlled by the temperature
      profile, which reaches temperatures from 50 to 65 degrees C for several days.
      Despite these high temperatures, mesophilic Enterobacteriaceae (including
      Cronobacter) and bacilli are present throughout Daqu fermentation. This study
      aimed to determine whether Daqu spontaneous solid-state fermentation selects for
      heat-resistant variants of these organisms. Heat resistance in Enterobacteriaceae
      is mediated by the locus of heat resistance (LHR). One LHR-positive strain of
      Kosakonia cowanii was identified in Daqu, and it exhibited higher heat resistance
      than the LHR-negative K. cowanii isolated from malted oats. Heat resistance in
      Bacillus endospores is mediated by the spoVA 2mob operon. Out of 10 Daqu isolates
      of the species Bacillus licheniformis, Brevibacillus parabrevis, Bacillus
      subtilis, Bacillus amyloliquefaciens, and Bacillus velezensis, 5 did not contain
      spoVA 2mob, 3 contained one copy, and 2 contained two copies. The presence and
      copy number of the spoVA 2mob operon increased the resistance of spores to
      treatment with 110 degrees C. To confirm the selection of LHR- and spoVA 2mob
      positive strains during Daqu fermentation, the copy numbers of these genetic
      elements in Daqu samples were quantified by quantitative PCR (qPCR). The
      abundance of LHR and the spoVA 2mob operon in community DNA relative to that of
      total bacterial 16S rRNA genes increased 3-fold and 5-fold, respectively, during
      processing. In conclusion, culture-dependent and culture-independent analyses
      suggest that Daqu fermentation selects for heat-resistant Enterobacteriaceae and
      bacilli.IMPORTANCE Daqu fermentations select for mobile genetic elements
      conferring heat resistance in Enterobacteriaceae and bacilli. The locus of heat
      resistance (LHR), a genomic island conferring heat resistance in
      Enterobacteriaceae, and the spoVA 2mob operon, conferring heat resistance on
      bacterial endospores, were enriched 3- to 5-fold during Daqu fermentation and
      maturation. It is therefore remarkable that the LHR and the spoVA 2mob operon are
      accumulated in the same food fermentation. The presence of heat-resistant
      Kosakonia spp. and Bacillus spp. in Daqu is not of concern for food safety;
      however, both genomic islands are mobile and transferable to pathogenic bacteria
      or toxin-producing bacteria by horizontal gene transfer. The identification of
      the LHR and the spoVA 2mob operon as indicators of fitness of Enterobacteriaceae
      and bacilli in Daqu fermentation provides insights into environmental sources of
      heat-resistant organisms that may contaminate the food supply.

PMID- 30120121
TI  - Antigen-specific antibody Fc glycosylation enhances humoral immunity via the
      recruitment of complement.
AB  - HIV-specific broadly neutralizing antibodies (bNAbs) confer protection after
      passive immunization, but the immunological mechanisms that drive their
      development are poorly understood. Structural features of bNAbs indicate that
      they originate from extensive germinal center (GC) selection, which relies on
      persistent GC activity. However, why a fraction of infected individuals are able
      to successfully drive more effective affinity maturation is unclear. Delivery of
      antigens in the form of antibody-immune complexes (ICs), which bind to complement
      receptors (CRs) or Fc receptors (FcRs) on follicular dendritic cells, represents
      an effective mechanism for antigen delivery to the GC. We sought to define
      whether IC-FcR or CR interactions differ among individuals who develop bNAb
      responses to HIV. Enhanced Fc effector functions and FcR/CR interactions, via
      altered Fc glycosylation profiles, were observed among individuals with
      neutralizing antibody responses to HIV compared with those without neutralizing
      antibody activity. Moreover, both polyclonal neutralizer ICs and monoclonal IC
      mimics of neutralizer antibodies induced higher antibody titers, higher-avidity
      antibodies, and expanded GC B cell reactions after immunization of mice via
      accelerated antigen deposition within B cell follicles in a complement-dependent
      manner. Thus, these data point to a direct role for altered Fc profile/complement
      interactions in shaping the maturation of the humoral immune response, providing
      insights into how GC activity may be enhanced to drive affinity maturation in
      next-generation vaccine approaches.

PMID- 30120122
TI  - Human NK Cells Lyse Th2-Polarizing Dendritic Cells via NKp30 and DNAM-1.
AB  - Cross-talk between NK cells and dendritic cells (DCs) is important in Th1 immune
      responses, including antitumor immunity and responses to infections. DCs also
      play a crucial role in polarizing Th2 immunity, but the impact of NK cell-DC
      interactions in this context remains unknown. In this study, we stimulated human
      monocyte-derived DCs in vitro with different pathogen-associated molecules: LPS
      or polyinosinic-polycytidylic acid, which polarize a Th1 response, or soluble egg
      Ag from the helminth worm Schistosoma mansoni, a potent Th2-inducing Ag. Th2
      polarizing DCs were functionally distinguishable from Th1-polarizing DCs, and
      both showed distinct morphology and dynamics from immature DCs. We then assessed
      the outcome of autologous NK cells interacting with these differently stimulated
      DCs. Confocal microscopy showed polarization of the NK cell microtubule
      organizing center and accumulation of LFA-1 at contacts between NK cells and
      immature or Th2-polarizing DCs but not Th1-polarizing DCs, indicative of the
      assembly of an activating immune synapse. Autologous NK cells lysed immature DCs
      but not DCs treated with LPS or polyinosinic-polycytidylic acid as reported
      previously. In this study, we demonstrated that NK cells also degranulated in the
      presence of Th2-polarizing DCs. Moreover, time-lapse live-cell microscopy showed
      that DCs that had internalized fluorescently labeled soluble egg Ag were
      efficiently lysed. Ab blockade of NK cell-activating receptors NKp30 or DNAM-1
      abrogated NK cell lysis of Th2-polarizing DCs. Thus, these data indicate a
      previously unrecognized role of NK cell cytotoxicity and NK cell-activating
      receptors NKp30 and DNAM-1 in restricting the pool of DCs involved in Th2 immune
      responses.

PMID- 30120124
TI  - CSF-1 in Inflammatory and Arthritic Pain Development.
AB  - Pain is one of the most debilitating symptoms in many diseases for which there is
      inadequate management and understanding. CSF-1, also known as M-CSF, acts via its
      receptor (CSF-1R, c-Fms) to regulate the development of the monocyte/macrophage
      lineage and to act locally in tissues to control macrophage numbers and function.
      It has been implicated in the control of neuropathic pain via a central action on
      microglia. We report in this study that systemic administration of a neutralizing
      anti-CSF-1R or CSF-1 mAb inhibits the development of inflammatory pain induced by
      zymosan, GM-CSF, and TNF in mice. This approach also prevented but did not
      ameliorate the development of arthritic pain and optimal disease driven by the
      three stimuli in mice, suggesting that CSF-1 may only be relevant when the
      driving inflammatory insults in tissues are acute and/or periodic. Systemic CSF-1
      administration rapidly induced pain and enhanced the arthritis in an inflamed
      mouse joint, albeit via a different pathway(s) from that used by systemic GM-CSF
      and TNF. It is concluded that CSF-1 can function peripherally during the
      generation of inflammatory pain and hence may be a target for such pain and
      associated disease, including when the clinically important cytokines, TNF and GM
      CSF, are involved. Our findings have ramifications for the selection and design
      of anti-CSF-1R/CSF-1 trials.

PMID- 30120123
TI  - Dysregulated Calcium Homeostasis in Cystic Fibrosis Neutrophils Leads to
      Deficient Antimicrobial Responses.
AB  - Cystic fibrosis (CF), one of the most common human genetic diseases worldwide, is
      caused by a defect in the CF transmembrane conductance regulator (CFTR). Patients
      with CF are highly susceptible to infections caused by opportunistic pathogens
      (including Burkholderia cenocepacia), which induce excessive lung inflammation
      and lead to the eventual loss of pulmonary function. Abundant neutrophil
      recruitment into the lung is a key characteristic of bacterial infections in CF
      patients. In response to infection, inflammatory neutrophils release reactive
      oxygen species and toxic proteins, leading to aggravated lung tissue damage in
      patients with CF. The present study shows a defect in reactive oxygen species
      production by mouse Cftr-/- , human F508del-CFTR, and CF neutrophils; this
      results in reduced antimicrobial activity against B. cenocepacia Furthermore,
      dysregulated Ca2+ homeostasis led to increased intracellular concentrations of
      Ca2+ that correlated with significantly diminished NADPH oxidase response and
      impaired secretion of neutrophil extracellular traps in human CF neutrophils.
      Functionally deficient human CF neutrophils recovered their antimicrobial killing
      capacity following treatment with pharmacological inhibitors of Ca2+ channels and
      CFTR channel potentiators. Our findings suggest that regulation of neutrophil
      Ca2+ homeostasis (via CFTR potentiation or by the regulation of Ca2+ channels)
      can be used as a new therapeutic approach for reestablishing immune function in
      patients with CF.

PMID- 30120127
TI  - Wettability in complex porous materials, the mixed-wet state, and its
      relationship to surface roughness.
AB  - A quantitative in situ characterization of the impact of surface roughness on
      wettability in porous media is currently lacking. We use reservoir condition
      micrometer-resolution X-ray tomography combined with automated methods for the
      measurement of contact angle, interfacial curvature, and surface roughness to
      examine fluid/fluid and fluid/solid interfaces inside a porous material. We study
      oil and water in the pore space of limestone from a giant producing oilfield,
      acquiring millions of measurements of curvature and contact angle on three
      millimeter-sized samples. We identify a distinct wetting state with a broad
      distribution of contact angle at the submillimeter scale with a mix of water-wet
      and water-repellent regions. Importantly, this state allows both fluid phases to
      flow simultaneously over a wide range of saturation. We establish that, in media
      that are largely water wet, the interfacial curvature does not depend on solid
      surface roughness, quantified as the local deviation from a plane. However, where
      there has been a significant wettability alteration, rougher surfaces are
      associated with lower contact angles and higher interfacial curvature. The
      variation of both contact angle and interfacial curvature increases with the
      local degree of roughness. We hypothesize that this mixed wettability may also be
      seen in biological systems to facilitate the simultaneous flow of water and
      gases; furthermore, wettability-altering agents could be used in both geological
      systems and material science to design a mixed-wetting state with optimal process
      performance.

PMID- 30120128
TI  - Repeatability and comparability of peripapillary vessel density measurements of
      high-density and non-high-density optical coherence tomography angiography scans
      in normal and glaucoma eyes.
AB  - AIMS: To compare the peripapillary vessel density (VD) measurements of high
      density (HD) and non-HD optical coherence tomography angiography (OCTA) scans in
      normal and glaucoma eyes, and to evaluate the intrasession repeatability of VD
      measurements of HD scans. METHODS: In a cross-sectional study, 46 normal (33
      subjects) and 89 glaucoma (64 patients) eyes underwent 3 HD and 1 non-HD optic
      nerve head OCTA scans in the same session. Agreement in VD measurements between
      HD and non-HD scans was assessed using Bland and Altman analysis. Repeatability
      of the VD measurements of HD scans was assessed using within-subject coefficient
      of repeatability (CRw) and variation (CVw). RESULTS: The mean difference in the
      VDs ranged between 0.7% (temporal sector VD) and 2.0% (inferonasal sector VD),
      with HD scans showing significantly greater VD values than non-HD scans. The 95%
      limits of agreement (LoA) in glaucoma eyes ranged between -2.0% and 5.0% for
      whole enface VD and between -4.8% and 9.6% for superotemporal VD. CRw (%) and CVw
      (%) of VD measurements of HD scans ranged from 3.0 to 4.9 and from 2.0 to 3.1 in
      normal eyes. The same ranged from 3.2 to 6.7 and from 2.6 to 4.8, respectively,
      in glaucoma eyes. CONCLUSIONS: VD of HD scans was higher than that of non-HD
      scans. The wide 95% LoA indicates that the VD measurements of HD and non-HD scans
      cannot be used interchangeably. Test-retest repeatability of VDs on HD scans was
      as high as 6%. These results should be considered while using OCTA for
      longitudinal evaluation of glaucoma.

PMID- 30120129
TI  - Variability in the ocular phenotype in mucopolysaccharidosis.
AB  - PURPOSE: Mucopolysaccharidoses (MPSs) are a heterogeneous group of lysosomal
      storage disorders. Ocular complications (such as corneal clouding, retinopathy
      and optic neuropathy) are common. Notably, there is a paucity of data on the
      effect of genotype and systemic treatments (enzyme replacement therapy or
      haematopoietic stem cell transplantation) on the ocular phenotype in MPS. We
      prospectively studied the ocular features of patients with MPSI (Hurler/Hurler
      Scheie/Scheie), MPSIV (Morquio) and MPSVI (Maroteaux-Lamy), to evaluate the
      effect of different therapeutic interventions and to correlate the findings with
      genetic and biomarker data. METHODS: Prospective observational cohort study.
      Study participants underwent detailed ocular examination including visual acuity;
      assessment of corneal clouding (Iris camera Corneal Opacification Measure score
      and Pentacam densitometry) and retinal and optic nerve imaging (optical coherence
      tomography and wide-field fundus imaging). Data on genotype, biomarkers and
      delivered therapies (type and length of treatment) were also collected for each
      patient where available. RESULTS: Overall, 21 patients with MPSI, 4 patients with
      MPSIV and 3 patients with MPSVI were recruited. Corneal clouding scores were
      higher in MPSI compared with MPSIV and MPSVI. Retinopathy was evident in patients
      with MPSI only. Association was observed between corneal clouding and biomarkers
      in MPSI, MPSIV and MPSVI. However, no clear association was seen between genotype
      or treatment type and ocular phenotype. CONCLUSIONS: The ocular phenotype in MPS
      is variable, with corneal clouding occurring in MPSI, MPSIV and MPSVI, and
      retinopathy in MPSI only. There was an association between corneal clouding and
      efficacy of systemic treatment as measured by biomarkers.

PMID- 30120125
TI  - Material microenvironmental properties couple to induce distinct transcriptional
      programs in mammalian stem cells.
AB  - Variations in a multitude of material microenvironmental properties have been
      observed across tissues in vivo, and these have profound effects on cell
      phenotype. Phenomenological experiments have suggested that certain of these
      features of the physical microenvironment, such as stiffness, could sensitize
      cells to other features; meanwhile, mechanistic studies have detailed a number of
      biophysical mechanisms for this sensing. However, the broad molecular
      consequences of these potentially complex and nonlinear interactions bridging
      from biophysical sensing to phenotype have not been systematically characterized,
      limiting the overall understanding and rational deployment of these biophysical
      cues. Here, we explore these interactions by employing a 3D cell culture system
      that allows for the independent control of culture substrate stiffness, stress
      relaxation, and adhesion ligand density to systematically explore the
      transcriptional programs affected by distinct combinations of biophysical
      parameters using RNA-seq. In mouse mesenchymal stem cells and human cortical
      neuron progenitors, we find dramatic coupling among these substrate properties,
      and that the relative contribution of each property to changes in gene expression
      varies with cell type. Motivated by the bioinformatic analysis, the stiffness of
      hydrogels encapsulating mouse mesenchymal stem cells was found to regulate the
      secretion of a wide range of cytokines, and to accordingly influence
      hematopoietic stem cell differentiation in a Transwell coculture model. These
      results give insights into how biophysical features are integrated by cells
      across distinct tissues and offer strategies to synthetic biologists and
      bioengineers for designing responses to a cell's biophysical environment.

PMID- 30120126
TI  - Redox-coupled quinone dynamics in the respiratory complex I.
AB  - Complex I couples the free energy released from quinone (Q) reduction to pump
      protons across the biological membrane in the respiratory chains of mitochondria
      and many bacteria. The Q reduction site is separated by a large distance from the
      proton-pumping membrane domain. To address the molecular mechanism of this long
      range proton-electron coupling, we perform here full atomistic molecular dynamics
      simulations, free energy calculations, and continuum electrostatics calculations
      on complex I from Thermus thermophilus We show that the dynamics of Q is redox
      state-dependent, and that quinol, QH2, moves out of its reduction site and into a
      site in the Q tunnel that is occupied by a Q analog in a crystal structure of
      Yarrowia lipolytica We also identify a second Q-binding site near the opening of
      the Q tunnel in the membrane domain, where the Q headgroup forms strong
      interactions with a cluster of aromatic and charged residues, while the Q tail
      resides in the lipid membrane. We estimate the effective diffusion coefficient of
      Q in the tunnel, and in turn the characteristic time for Q to reach the active
      site and for QH2 to escape to the membrane. Our simulations show that Q moves
      along the Q tunnel in a redox-state-dependent manner, with distinct binding sites
      formed by conserved residue clusters. The motion of Q to these binding sites is
      proposed to be coupled to the proton-pumping machinery in complex I.

PMID- 30120130
TI  - Fundus examination of 199 851 newborns by digital imaging in China: a multicentre
      cross-sectional study.
AB  - BACKGROUND: The prevalence of ocular abnormalities of newborn in China has seldom
      been reported. To report the implementation of digital imaging in ocular
      screening of all newborns in multiple centres in China and to describe the
      abnormal findings of fundus examination, we did the cross-sectional study.
      METHODS: Fundus examinations were performed on newborns within the 42 days after
      birth using a RetCam wide-field digital imaging system. Digital images of the
      posterior pole, superior, nasal and temporal retinal fields of each participant
      were taken. All newborns were from eights centres across China from January 2009
      to July 2017. RESULTS: A total of 199 851 newborns were included in the study. We
      detected 18 198 (9.11%) abnormal cases. The most frequent abnormality was severe
      retinal haemorrhage (RH) found in 12 810 cases (6.41%). The other anomalies
      included familial exudative vitreoretinopathy, retinopathy of prematurity,
      abnormal fundus pigmentation, subconjunctival haemorrhage, choroidal coloboma,
      idiopathic retinal venous tortuosity, exudative changes and other anomalies with
      uncertain identities. CONCLUSION: This large-scale study of newborn fundus
      examination showed a relatively high prevalence of ocular abnormalities. Hundreds
      of neonates with rare disorders that severely impair ocular health were also
      detected at an early age. The long-term impact of other anomalies including RHs
      on the ocular system should be investigated by a perspective study. Our study
      suggested that fundus examination of newborns can play a beneficial role in
      ocular health.

PMID- 30120131
TI  - Dual antiplatelet therapy pretreatment in IV thrombolysis for acute ischemic
      stroke.
AB  - OBJECTIVE: We sought to determine the safety and efficacy of IV thrombolysis
      (IVT) in acute ischemic stroke (AIS) patients with a history of dual antiplatelet
      therapy pretreatment (DAPP) in a prospective multicenter study. METHODS: We
      compared the following outcomes between DAPP+ and DAPP- IVT-treated patients
      before and after propensity score matching (PSM): symptomatic intracranial
      hemorrhage (sICH), asymptomatic intracranial hemorrhage, favorable functional
      outcome (modified Rankin Scale score 0-1), and 3-month mortality. RESULTS: Among
      790 IVT patients, 58 (7%) were on DAPP before stroke (mean age 68 +/- 13 years;
      57% men; median NIH Stroke Scale score 8). DAPP+ patients were older with more
      risk factors compared to DAPP- patients. The rates of sICH were similar between
      groups (3.4% vs 3.2%). In multivariable analyses adjusting for potential
      confounders, DAPP was associated with higher odds of asymptomatic intracranial
      hemorrhage (odds ratio = 3.53, 95% confidence interval: 1.47-8.47; p = 0.005) but
      also with a higher likelihood of 3-month favorable functional outcome (odds ratio
      = 2.41, 95% confidence interval: 1.06-5.46; p = 0.035). After propensity score
      matching, 41 DAPP+ patients were matched to 82 DAPP- patients. The 2 groups did
      not differ in any of the baseline characteristics or safety and efficacy
      outcomes. CONCLUSIONS: DAPP is not associated with higher rates of sICH and 3
      month mortality following IVT. DAPP should not be used as a reason to withhold
      IVT in otherwise eligible AIS candidates. CLASSIFICATION OF EVIDENCE: This study
      provides Class III evidence that for IVT-treated patients with AIS, DAPP is not
      associated with a significantly higher risk of sICH. The study lacked the
      precision to exclude a potentially meaningful increase in sICH bleeding risk.

PMID- 30120132
TI  - Inclusion of optic nerve involvement in dissemination in space criteria for
      multiple sclerosis.
AB  - OBJECTIVE: To investigate the effect of including optic nerve involvement in
      dissemination in space (DIS) criteria for diagnosis of multiple sclerosis (MS) in
      patients with clinically isolated syndrome (CIS). METHODS: We studied 160
      patients with CIS: 129 with optic neuritis (ON) and 31 with non-ON CIS. MRI
      brain/spinal cord was done at the time of presentation and a follow-up MRI brain
      after 3-12 months. We evaluated optic nerve involvement clinically or with visual
      evoked potentials (VEPs, n = 42). We investigated the performance of the McDonald
      2017 DIS criteria and modified DIS criteria including optic nerve involvement for
      development of clinically definite MS after ~15 years. RESULTS: In the ON group,
      including symptomatic optic nerve involvement identified an additional 15
      patients with DIS. The modified DIS criteria that included optic nerve
      involvement were more sensitive (95% vs 83%) and more accurate (81% vs 78%) than
      the McDonald 2017 DIS criteria, but less specific (57% vs 68%). In combination
      with dissemination in time criteria, the modified DIS criteria remained more
      sensitive (83% vs 74%) and accurate (81% vs 75%), and the specificity was the
      same (77%). Including asymptomatic optic nerve involvement in DIS the non-ON
      group did not identify any additional patients and the performance of the
      McDonald 2017 criteria and the modified criteria was the same. CONCLUSION: The
      inclusion of symptomatic optic nerve involvement in DIS in patients with ON
      improved the overall performance of MS diagnostic criteria. Including
      asymptomatic optic nerve involvement in DIS in patients with a non-ON CIS may be
      of limited value. CLASSIFICATION OF EVIDENCE: This study provides Class III
      evidence that for patients with suspected MS, inclusion of symptomatic optic
      nerve involvement in DIS criteria improves the overall performance of diagnostic
      criteria for MS.

PMID- 30120134
TI  - Axonal peripheral neuropathy in propionic acidemia: A severe side effect of long
      term metronidazole therapy.

PMID- 30120133
TI  - Removing high-frequency oscillations: A prospective multicenter study on seizure
      outcome.
AB  - OBJECTIVE: To evaluate the use of interictal high-frequency oscillations (HFOs)
      in epilepsy surgery for prediction of postsurgical seizure outcome in a
      prospective multicenter trial. METHODS: We hypothesized that a seizure-free
      outcome could be expected in patients in whom the surgical planning included the
      majority of HFO-generating brain tissue while a poor seizure outcome could be
      expected in patients in whom only a few such areas were planned to be resected.
      Fifty-two patients were included from 3 tertiary epilepsy centers during a 1-year
      period. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were automatically
      detected during slow-wave sleep with chronic intracranial EEG in 2 centers and
      acute intraoperative electrocorticography in 1 patient. RESULTS: There was a
      correlation between the removal of HFO-generating regions and seizure-free
      outcome at the group level for all patients. No correlation was found, however,
      for the center-specific analysis, and an individual prognostication of seizure
      outcome was true in only 36 patients (67%). Moreover, some patients became
      seizure-free without removal of the majority of HFO-generating tissue. The
      investigation of influencing factors, including comparisons of visual and
      automatic analysis, using a threshold analysis for areas with high HFO activity,
      and excluding contacts bordering the resection, did not result in improved
      prognostication. CONCLUSIONS: On an individual patient level, a prediction of
      outcome was not possible in all patients. This may be due to the analysis
      techniques used. Alternatively, HFOs may be less specific for epileptic tissue
      than earlier studies have indicated.

PMID- 30120135
TI  - Validation of MRC Centre MRI calf muscle fat fraction protocol as an outcome
      measure in CMT1A.
AB  - OBJECTIVE: To translate the quantitative MRC Centre MRI protocol in Charcot-Marie
      Tooth disease type 1A (CMT1A) to a second site; validate its responsiveness in an
      independent cohort; and test the benefit of participant stratification to
      increase outcome measure responsiveness. METHODS: Three healthy volunteers were
      scanned for intersite standardization. For the longitudinal patient study, 11
      patients with CMT1A were recruited with 10 patients rescanned at a 12-month
      interval. Three-point Dixon MRI of leg muscles was performed to generate fat
      fraction (FF) maps, transferred to a central site for quality control and
      analysis. Clinical data collected included CMT Neuropathy Score. RESULTS: Test
      retest reliability of FF within individual healthy calf muscles at the remote
      site was excellent: intraclass correlation coefficient 0.79, limits of agreement 
      0.67 to +0.85 %FF. In patients, mean calf muscle FF was 21.0% and correlated
      strongly with disease severity and age. Calf muscle FF significantly increased
      over 12 months (+1.8 +/- 1.7 %FF, p = 0.009). Patients with baseline FF >10%
      showed a 12-month FF increase of 2.9% +/- 1.3% (standardized response mean =
      2.19). CONCLUSIONS: We have validated calf muscle FF as an outcome measure in an
      independent cohort of patients with CMT1A. Responsiveness is significantly
      improved by enrolling a stratified patient cohort with baseline calf FF >10%.

PMID- 30120136
TI  - Work-relatedness of lumbosacral radiculopathy syndrome: Review and dose-response
      meta-analysis.
AB  - OBJECTIVE: Clinicians need to know whether lumbosacral radiculopathy syndrome
      (LRS) can be attributed to work. This review describes what work-related risk
      factors are associated with LRS. METHODS: A systematic review was performed in
      PubMed and Embase. Inclusion criteria were that LRS was diagnosed by a clinician
      and workers exposed to work-related risk factors were compared to workers less or
      not exposed. A quality assessment and a meta-analysis were performed, including a
      dose-response analysis. RESULTS: The search resulted in 7,350 references and 24
      studies that fulfilled the inclusion criteria: 19 studies were rated as having a
      high risk of bias and 5 as having a low risk of bias. The median number of LRS
      patients per study were 209 (interquartile range 124-504) and the total number of
      participants was 10,142. The meta-analysis revealed significant associations with
      heavy physically demanding work (odds ratio [OR] 2.03, 95% confidence interval
      [CI] 1.48-2.79), bending or twisting of the trunk (OR 2.43, 95% CI 1.67-3.55),
      and lifting and carrying in combination with bending or twisting of the trunk (OR
      2.84, 95% CI 2.18-3.69). No significant associations were found for professional
      driving (OR 1.46, 95% CI 0.90-2.35) or sitting (OR 1.08, 95% CI 0.49-2.38). A
      dose-response relation was present per 5 years of exposure for bending (OR 1.12,
      95% CI 1.04-1.20), lifting (OR 1.08, 95% CI 1.02-1.14) and the combination of
      bending and lifting (OR 1.14, 95% CI 1.01-1.29). CONCLUSIONS: Moderate to high
      quality evidence is available that LRS can be classified as a work-related
      disease depending on the level of exposure to bending of the trunk or lifting and
      carrying. Professional driving and sitting were not significantly associated with
      LRS.

PMID- 30120137
TI  - Vemurafenib and cobimetinib overcome resistance to vemurafenib in BRAF-mutant
      ganglioglioma.

PMID- 30120139
TI  - Optic neuritis in the diagnosis of MS: More than meets the eye.

PMID- 30120138
TI  - Fremanezumab for preventive treatment of migraine: Functional status on headache
      free days.
AB  - OBJECTIVE: To evaluate the effect of fremanezumab on the functional status on
      headache-free days in phase 2 episodic migraine (EM) and chronic migraine (CM)
      studies. METHODS: Functional status data were collected prospectively via the
      electronic headache diary on all headache-free days by patients answering
      questions regarding work/school/household chore performance, speed of work
      completion, concentration, and feeling of fatigue. Individuals with EM receiving
      monthly doses of fremanezumab 225 mg (n = 96) or 675 mg (n = 97) or placebo (n =
      104) were compared. Individuals with CM receiving fremanezumab 675 mg followed by
      monthly 225 mg (n = 88) and 900 mg (n = 86) were also independently compared to
      those receiving placebo (n = 89). RESULTS: In patients with EM, compared to
      patients receiving placebo, those receiving fremanezumab experienced an increased
      number of headache-free days with normal function in work/school/household chore
      performance and concentration/mental fatigue measures compared to their baseline
      over the entire treatment period (all p < 0.005). An increased number of headache
      free days with normal functional performance for some measures was also found in
      the CM group in those treated with fremanezumab. CONCLUSION: There was an
      increased number of headache-free days with normal functional performance on all
      measures for the patients with EM and some measures for patients with CM in the
      fremanezumab-treated groups. Further research is required to confirm these
      findings in a prospective study and to clarify the underlying mechanism(s).
      CLINICALTRIALSGOV IDENTIFIER: NCT02025556 and NCT02021773. CLASSIFICATION OF
      EVIDENCE: This study provides Class II evidence that for patients with migraine,
      fremanezumab increases normal functional performance on headache-free days.

PMID- 30120141
TI  - Question 1: Do children with Down syndrome benefit from extra vaccinations?

PMID- 30120142
TI  - Two subtypes of symptomatic joint hypermobility: a descriptive study using latent
      class analysis.
AB  - OBJECTIVE: To investigate a cohort of children with symptomatic joint
      hypermobility. METHODS: Case notes for 318 children with joint hypermobility
      attending a rheumatology clinic were reviewed for clinical presentation, medical
      history, psychosocial factors and physical examination findings. Seven key
      variables were extracted and used as indicator variables in a latent class
      analysis to estimate the presence and number of subgroups of children with
      symptomatic joint hypermobility. RESULTS: Two subgroups with differing clinical
      presentations were identified accounting for age and gender: an 'athletic
      persistent' class (62%) characterised by higher probabilities for recurrent and
      chronic musculoskeletal pain, and less severe hypermobility; and a 'systemic
      profound' class (38%) characterised by generalised hypermobility, recurrent
      musculoskeletal pain, gastro-oesophageal reflux and motor delay. CONCLUSION:
      Findings suggest the presence of two distinct presentations of children with
      hypermobility. This finding may be important for clinical decision-making and
      management of this group of children.

PMID- 30120143
TI  - An infant with a persistent cough and an unusual course of the nasogastric tube.

PMID- 30120140
TI  - OrthoList 2: A New Comparative Genomic Analysis of Human and Caenorhabditis
      elegans Genes.
AB  - OrthoList, a compendium of Caenorhabditis elegans genes with human orthologs
      compiled in 2011 by a meta-analysis of four orthology-prediction methods, has
      been a popular tool for identifying conserved genes for research into biological
      and disease mechanisms. However, the efficacy of orthology prediction depends on
      the accuracy of gene-model predictions, an ongoing process, and orthology
      prediction algorithms have also been updated over time. Here we present OrthoList
      2 (OL2), a new comparative genomic analysis between C. elegans and humans, and
      the first assessment of how changes over time affect the landscape of predicted
      orthologs between two species. Although we find that updates to the orthology
      prediction methods significantly changed the landscape of C. elegans-human
      orthologs predicted by individual programs and-unexpectedly-reduced agreement
      among them, we also show that our meta-analysis approach "buffered" against
      changes in gene content. We show that adding results from more programs did not
      lead to many additions to the list and discuss reasons to avoid assigning
      "scores" based on support by individual orthology-prediction programs; the
      treatment of "legacy" genes no longer predicted by these programs; and the
      practical difficulties of updating due to encountering deprecated, changed, or
      retired gene identifiers. In addition, we consider what other criteria may
      support claims of orthology and alternative approaches to find potential
      orthologs that elude identification by these programs. Finally, we created a new
      web-based tool that allows for rapid searches of OL2 by gene identifiers, protein
      domains [InterPro and SMART (Simple Modular Architecture Research Tool], or human
      disease associations ([OMIM (Online Mendelian Inheritence in Man], and also
      includes available RNA-interference resources to facilitate potential
      translational cross-species studies.

PMID- 30120145
TI  - Correction notice to paper "Agreement of treatment effects for mortality from
      routinely collected data and subsequent randomized trials: meta-epidemiological
      survey".

PMID- 30120147
TI  - Combinatorial interplay of RNA-binding proteins tunes levels of mitochondrial
      mRNA in trypanosomes.
AB  - MRP1/2 is a heteromeric protein complex that functions in the trypanosomatid
      mitochondrion as part of the RNA editing machinery, which facilitates multiple
      targeted insertions and deletions of uridines. MRP1/2 was shown to interact with
      MRB8170, which initiates RNA editing by marking pre-edited mRNAs, while TbRGG2 is
      required for its efficient progression on pan-edited mRNAs. Both MRP1/2 and
      TbRGG2 are capable of modulating RNA-RNA interactions in vitro. As determined by
      using iCLIP and RIP-qPCR, RNAs bound to MRP1/2 are characterized and compared
      with those associated with MRB8170 and TbRGG2. We provide evidence that MRP1 and
      MRB8170 have correlated binding and similar RNA crosslinking peak profiles over
      minimally and never-edited mRNAs. Our results suggest that MRP1 assists MRB8170
      in RNA editing on minimally edited mRNAs.

PMID- 30120148
TI  - My journey in the discovery of nucleotide sugar transporters of the Golgi
      apparatus.
AB  - Defects in protein glycosylation can have a dramatic impact on eukaryotic cells
      and is associated with mental and developmental pathologies in humans. The
      studies outlined below illustrate how a basic biochemical problem in the
      mechanisms of protein glycosylation, specifically substrate transporters of
      nucleotide sugars, including ATP and 3'-phosphoadenyl-5'-phosphosulfate (PAPS),
      in the membrane of the Golgi apparatus and endoplasmic reticulum, expanded into
      diverse biological systems from mammals, including humans, to yeast, roundworms,
      and protozoa. Using these diverse model systems allowed my colleagues and me to
      answer fundamental biological questions that enabled us to formulate far-reaching
      hypotheses and expanded our knowledge of human diseases caused by malfunctions in
      the metabolic processes involved.

PMID- 30120144
TI  - SNARE-mediated membrane fusion arrests at pore expansion to regulate the volume
      of an organelle.
AB  - Constitutive membrane fusion within eukaryotic cells is thought to be controlled
      at its initial steps, membrane tethering and SNARE complex assembly, and to
      rapidly proceed from there to full fusion. Although theory predicts that fusion
      pore expansion faces a major energy barrier and might hence be a rate-limiting
      and regulated step, corresponding states with non-expanding pores are difficult
      to assay and have remained elusive. Here, we show that vacuoles in living yeast
      are connected by a metastable, non-expanding, nanoscopic fusion pore. This is
      their default state, from which full fusion is regulated. Molecular dynamics
      simulations suggest that SNAREs and the SM protein-containing HOPS complex
      stabilize this pore against re-closure. Expansion of the nanoscopic pore to full
      fusion can thus be triggered by osmotic pressure gradients, providing a simple
      mechanism to rapidly adapt organelle volume to increases in its content.
      Metastable, nanoscopic fusion pores are then not only a transient intermediate
      but can be a long-lived, physiologically relevant and regulated state of SNARE
      dependent membrane fusion.

PMID- 30120146
TI  - Dual reporter genetic mouse models of pancreatic cancer identify an epithelial-to
      mesenchymal transition-independent metastasis program.
AB  - Epithelial-to-mesenchymal transition (EMT) is a recognized eukaryotic cell
      differentiation program that is also observed in association with invasive
      tumors. Partial EMT program in carcinomas imparts cancer cells with mesenchymal
      like features and is proposed as essential for metastasis. Precise determination
      of the frequency of partial EMT program in cancer cells in tumors and its
      functional role in metastases needs unraveling. Here, we employed mesenchymal
      cell reporter mice driven by alphaSMA-Cre and Fsp1-Cre with genetically
      engineered mice that develop spontaneous pancreatic ductal adenocarcinoma (PDAC)
      to monitor partial EMT program. Both alphaSMA- and Fsp1-Cre-mediated partial EMT
      programs were observed in the primary tumors. The established metastases were
      primarily composed of cancer cells without evidence for a partial EMT program, as
      assessed by our fate mapping approach. In contrast, metastatic cancer cells
      exhibiting a partial EMT program were restricted to isolated single cancer cells
      or micrometastases (3-5 cancer cells). Collectively, our studies identify large
      metastatic nodules with preserved epithelial phenotype and potentially unravel a
      novel metastasis program in PDAC.

PMID- 30120149
TI  - Down-regulation of micro-RNA-1 (miR-1) in lung cancer. Suppression of tumorigenic
      property of lung cancer cells and their sensitization to doxorubicin-induced
      apoptosis by miR-1.

PMID- 30120150
TI  - Identification of a novel cyclic AMP-response element (CRE-II) and the role of
      CREB-1 in the cAMP-induced expression of the survival motor neuron (SMN) gene.

PMID- 30120151
TI  - Mitochondrial transcription factor A and its downstream targets are up-regulated
      in a rat hepatoma.

PMID- 30120152
TI  - Role of de novo DNA methyltransferases and methyl CpG-binding proteins in gene
      silencing in a rat hepatoma.

PMID- 30120153
TI  - An elusive adenylate cyclase complicit in cholera is exposed.
AB  - The intestinal consequences of cholera enterotoxin are caused by activation of
      the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel
      through the actions of an as-yet-unknown adenylate cyclase. A new study hunts
      down this elusive enzyme, showing that mouse and human intestinal epithelium
      functionally and structurally pair adenylate cyclase isoform 6 (AC6) with CFTR.
      These findings provide important insights into the molecular mechanisms
      underlying the robust pathological activation of CFTR activity and promise new
      opportunities to treat cholera.

PMID- 30120154
TI  - Correction for Li et al., "Novel Gene Clusters and Metabolic Pathway Involved in
      3,5,6-Trichloro-2-Pyridinol Degradation by Ralstonia sp. Strain T6".

PMID- 30120155
TI  - Correction for Mattingly et al., "Multiple Environmental Factors Influence the
      Importance of the Phosphodiesterase DipA upon Pseudomonas aeruginosa Swarming".

PMID- 30120156
TI  - Another Chapter of the Right Versus Left Story: Is Primary Tumor Location a
      Prognostic Feature in RAS Mutant Metastatic Colorectal Cancer?
AB  - BACKGROUND: The prognostic value of primary tumor location (PTL) in patients with
      metastatic colorectal cancer (mCRC) was reported by recent analyses in RAS wild
      type patients. Here, we investigated the prognostic value of PTL in RAS mutated
      mCRC patients. MATERIALS AND METHODS: PTL was defined as left or right if distal
      or proximal to the splenic flexure. Primary endpoint was overall survival (OS)
      according to PTL. Subgroup analyses were conducted according to time to
      metastases and RAS mutation subtypes. RESULTS: Five hundred sixty-four patients
      were included. Left- and right-sided cases were 65% and 35%, respectively. No
      difference in OS was detected according to PTL (hazard ratio [HR] = 0.99, p =
      .964). No difference in OS was observed in right versus left when looking at
      synchronous (HR 0.92, p = .557) or metachronous (HR 1.07, p = .807) patients.
      CONCLUSION: No OS difference was detected in RAS mutated mCRC. Molecular and
      clinical features able to improve prognosis and treatment strategies in this
      setting are needed.

PMID- 30120157
TI  - Impact of Guideline-Discordant Treatment on Cost and Health Care Utilization in
      Older Adults with Early-Stage Breast Cancer.
AB  - BACKGROUND: National Comprehensive Cancer Network (NCCN) guideline-based
      treatment is a marker of high-quality care. The impact of guideline discordance
      on cost and health care utilization is unclear. MATERIALS AND METHODS: This
      retrospective cohort study of Medicare claims data from 2012 to 2015 included
      women age >=65 with stage I-III breast cancer receiving care within the
      University of Alabama at Birmingham Cancer Community Network. Concordance with
      NCCN guidelines was assessed for treatment regimens. Costs to Medicare and health
      care utilization were identified from start of cancer treatment until death or
      available follow-up. Adjusted monthly cost and utilization rates were estimated
      using linear mixed effect and generalized linear models. RESULTS: Of 1,177
      patients, 16% received guideline-discordant treatment, which was associated with
      nonwhite race, estrogen receptor/progesterone receptor negative, human epidermal
      growth receptor 2 (HER2) positive, and later-stage cancer. Discordant therapy was
      primarily related to reduced-intensity treatments (single-agent chemotherapy,
      HER2-targeted therapy without chemotherapy, bevacizumab without chemotherapy,
      platinum combinations without anthracyclines). In adjusted models, average
      monthly costs for guideline-discordant patients were $936 higher compared with
      concordant (95% confidence limits $611, $1,260). For guideline-discordant
      patients, adjusted rates of emergency department visits and hospitalizations per
      thousand observations were 25% higher (49.9 vs. 39.9) and 19% higher (24.0 vs.
      20.1) per month than concordant patients, respectively. CONCLUSION: One in six
      patients with early-stage breast cancer received guideline-discordant care,
      predominantly related to undertreatment, which was associated with higher costs
      and rates of health care utilization. Additional randomized trials are needed to
      test lower-toxicity regimens and guide clinicians in treatment for older breast
      cancer patients. IMPLICATIONS FOR PRACTICE: Previous studies lack details about
      types of deviations from chemotherapy guidelines that occur in older early-stage
      breast cancer patients. Understanding the patterns of guideline discordance and
      its impact on patient outcomes will be particularly important for these patients.
      This study found 16% received guideline-discordant care, predominantly related to
      reduced intensity treatment and associated with higher costs and rates of health
      care utilization. Increasing older adult participation in clinical trials should
      be a priority in order to fill the knowledge gap about how to treat older, less
      fit patients with breast cancer.

PMID- 30120159
TI  - Adjuvant Anthracyclines in Breast Cancer: What Is Their Role?
AB  - : Anthracyclines have been a mainstay of breast cancer therapy for decades, with
      strong evidence demonstrating their impact on breast cancer survival. However,
      concerns regarding rare but serious long-term toxicities including cardiotoxicity
      and hematologic malignancies have driven interest in alternative adjuvant therapy
      options with more favorable toxicity profiles. This article provides an update of
      data that help inform clinicians of the role anthracyclines should play in
      adjuvant breast cancer therapy. Two recently reported large randomized trials-the
      Anthracycline in Early Breast Cancer and Western German Study Plan B studies
      compared a taxane and cyclophosphamide regimen with an anthracycline, taxane, and
      cyclophosphamide regimen. Although the studies had conflicting results, together
      these studies suggest that the benefit of adjuvant anthracycline therapy over a
      nonanthracycline taxane-containing regimen is modest at best and may be primarily
      seen in patients with especially high-risk disease (i.e., triple-negative breast
      cancer, involvement of multiple lymph nodes). A third study-the MINDACT study
      compared an anthracycline-based regimen to a nonanthracycline regimen, with
      similar outcomes in both groups. Despite the toxicities, no adjuvant breast
      cancer regimen has been shown to be superior to an anthracycline-taxane regimen
      in high-risk patients. These data can directly inform clinical decision-making in
      determining which patients warrant use of adjuvant anthracycline therapy. Future
      research may focus on confirming subgroups for whom it is reasonable to forgo
      adjuvant anthracyclines and validating predictive biomarkers or scores for
      anthracycline benefit. IMPLICATIONS FOR PRACTICE: In patients with early breast
      cancer, the choice of adjuvant chemotherapy should be based on its effectiveness
      in reducing breast cancer recurrences and its short- and long-term toxicities.
      Although adjuvant anthracycline and taxane chemotherapy has the most data
      supporting its effectiveness, anthracyclines carry a small but important
      increased risk for cardiotoxicity and leukemia. Two recent clinical trials help
      describe the degree of benefit with adjuvant anthracycline therapy compared with
      taxane therapy alone. They suggest that in patients with hormone receptor
      positive breast cancer and limited lymph node involvement, nonanthracycline
      taxane-based adjuvant therapy may be adequate.

PMID- 30120158
TI  - Prognostic Understanding at Diagnosis and Associated Factors in Patients with
      Advanced Lung Cancer and Their Caregivers.
AB  - BACKGROUND: Prognostic understanding in advanced cancer patients and their
      caregivers may have an impact on the delivery of effective care. The aims of this
      study were to explore prognostic understanding at diagnosis in both patients with
      advanced lung cancer and their caregivers and to investigate correlates of their
      understanding. SUBJECTS, MATERIALS, AND METHODS: A total of 193 patients with
      newly diagnosed advanced lung cancer and their 167 caregivers were enrolled at 16
      hospitals in Japan. We assessed their perceptions of prognosis and goals of
      therapy and examined their associations with their sociodemographic
      characteristics, clinical status, quality of life, mood symptoms, and the status
      of disclosure of information by their treating physicians. RESULTS: One fifth of
      patients and caregivers (21.7% and 17.6%, respectively) mistakenly believed that
      the patients' cancer was "completely curable." Substantial proportions of them
      (16.9% and 10.3%, respectively) mistakenly believed that the primary goal of
      therapy was to remove all the cancer. Levels of anxiety and depression in both
      patients and caregivers were significantly higher among those who had accurate
      understanding of prognosis. In multivariate analyses, inaccurate perceptions of
      prognosis in patients were associated with sex, better emotional well-being, and
      lower lung cancer-specific symptom burden. Caregivers' inaccurate perceptions of
      patients' prognoses were associated with better performance status and better
      emotional well-being of patients. CONCLUSION: Substantial proportions of advanced
      lung cancer patients and their caregivers misunderstood their prognosis.
      Interventions to improve their accurate prognostic understanding should be
      developed with careful attention paid to its associated factors. IMPLICATIONS FOR
      PRACTICE: This study demonstrated that substantial proportions of patients with
      newly diagnosed advanced lung cancer and their caregivers had misunderstandings
      about their prognosis. Accurate perceptions of prognosis, which are indispensable
      in the delivery of effective care, were associated with elevated levels of
      anxiety and depression in both patients and caregivers, warranting psychosocial
      care and support for them immediately after diagnosis. Inaccurate perceptions of
      prognosis in patients were associated with better emotional well-being and lower
      lung cancer-specific symptom burden. Illness understanding in caregivers was
      associated with patients' physical and mental status. Those findings provide
      insight into how they obtain accurate illness understanding.

PMID- 30120162
TI  - In Reply.

PMID- 30120160
TI  - FDA Approval Summary: Vemurafenib for the Treatment of Patients with Erdheim
      Chester Disease with the BRAFV600 Mutation.
AB  - : On November 6, 2017, the U.S. Food and Drug Administration (FDA) granted
      regular approval to vemurafenib for the treatment of adult patients with Erdheim
      Chester disease (ECD) with BRAFV600 mutation. ECD is a type of histiocytosis, a
      rare disorder characterized by an abnormal accumulation and behavior of cells of
      the mononuclear phagocytic system, which includes antigen-processing cells,
      dendritic cells, monocytes, or macrophages. Recently published data confirm a
      frequency of 54% of BRAFV600E mutations in patients with ECD.Approval was based
      on a cohort of 22 patients who received 960 mg of vemurafenib twice daily within
      the VE Basket Trial (MO28072), a single-arm, multicenter, multiple cohort study.
      Patients in the ECD cohort had histologically confirmed ECD with BRAFV600
      mutations that were refractory to standard therapy. The ECD cohort achieved an
      overall response rate of 54.5% (95% confidence interval: 32.2-75.6), with a
      complete response rate of 4.5%. With a median duration of follow-up of 26.6
      months, the median duration of response has not been reached. The most frequently
      reported adverse reactions (>50%) in the ECD cohort were arthralgia, rash maculo
      papular, alopecia, fatigue, electrocardiogram QT interval prolonged, and skin
      papilloma. The median treatment duration for ECD patients in this study was 14.2
      months. This article describes the FDA review of the vemurafenib efficacy
      supplement for patients with ECD with BRAFV600 mutations. IMPLICATIONS FOR
      PRACTICE: Vemurafenib, an oral monotherapy targeting a mutation in BRAF, is the
      first U.S. Food and Drug Administration approval for the treatment of Erdheim
      Chester disease (ECD). ECD is an extremely rare hematopoietic neoplasm that
      represents clonal proliferation of myeloid progenitor cells. ECD may involve bone
      and one or more organ systems, primarily affecting adults in their 5th and 7th
      decades of life, with a slight male predominance. This approval provides an
      effective and reasonably safe therapy for patients with a serious and life
      threatening condition for which no approved therapy exists.

PMID- 30120163
TI  - FDA Approval Summary: Pembrolizumab for Recurrent Locally Advanced or Metastatic
      Gastric or Gastroesophageal Junction Adenocarcinoma Expressing PD-L1.
AB  - : On September 22, 2017, the U.S. Food and Drug Administration (FDA) granted
      accelerated approval for pembrolizumab (Keytruda, Merck & Co., Inc., Whitehouse
      Station, NJ) for the treatment of patients with recurrent, locally advanced or
      metastatic, gastric or gastroesophageal junction (GEJ) adenocarcinoma with
      disease progression on or after two or more systemic therapies, including
      fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate,
      HER2/neu-targeted therapy, and whose tumors express programmed death-ligand 1 (PD
      L1), as determined by an FDA-approved test. Approval was based on demonstration
      of durable overall response rate (ORR) in a multicenter, open-label, multicohort
      trial (KEYNOTE-059/Cohort 1) that enrolled 259 patients with locally advanced or
      metastatic gastric or GEJ adenocarcinoma. Among the 55% (n = 143) of patients
      whose tumors expressed PD-L1 based on a combined positive score >=1 and either
      were microsatellite stable or had undetermined microsatellite instability or
      mismatch repair status, the confirmed ORR as determined by blinded independent
      central review was 13.3% (95% CI, 8.2-20.0); 1.4% had complete responses.
      Response durations ranged from 2.8+ to 19.4+ months; 11 patients (58%) had
      response durations of 6 months or longer, and 5 patients (26%) had response
      durations of 12 months or longer. The most common (>=20%) adverse reactions of
      pembrolizumab observed in KEYNOTE-059/Cohort 1 were fatigue, decreased appetite,
      nausea, and constipation. The most frequent (>=2%) serious adverse drug reactions
      were pleural effusion, pneumonia, dyspnea, pulmonary embolism, and pneumonitis.
      Pembrolizumab was approved concurrently with the PD-L1 immunohistochemistry 22C3
      pharmDx test (Dako, Agilent, Santa Clara, CA) for selection of patients with
      gastric cancer for treatment with pembrolizumab based on PD-L1 tumor expression.
      IMPLICATIONS FOR PRACTICE: This report presents key information on the basis for
      Food and Drug Administration approval of pembrolizumab for the treatment of
      patients with locally advanced or metastatic gastric or GEJ adenocarcinoma whose
      tumors express PD-L1. The report discusses the basis for limiting the indication
      to patients with PD-L1-expressing tumors and the basis for recommending that PD
      L1 status be assessed using a fresh tumor specimen if PD-L1 expression is not
      detected in an archival gastric or GEJ cancer specimen.

PMID- 30120161
TI  - Single-Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or
      BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial).
AB  - LESSONS LEARNED: RAS- or BRAF-mutated metastatic colorectal cancers (mCRCs)
      progressing after first-line treatment have a poor prognosis.European and U.S.
      guidelines include the multikinase inhibitor regorafenib as a standard option for
      second-line therapy and beyond, based on the results of the randomized phase III
      CORRECT trial demonstrating improvement in survival.Although stopped prematurely
      for failing to accrue, the PREVIUM trial, the first prospective interventional
      study exploring regorafenib as second-line treatment for patients with mCRC
      bearing RAS or BRAF mutations, failed to demonstrate clinical activity in the
      population analyzed. BACKGROUND: Patients with RAS- or BRAF-mutated (mut)
      metastatic colorectal cancer (mCRC) progressing on first-line bevacizumab plus 5
      FU/irinotecan/oxaliplatin (FOLFOXIRI) have a poor prognosis. We aimed to assess
      the efficacy and safety of regorafenib in this population. METHODS: Regorafenib
      was administered daily for 3 weeks of each 4-week cycle until disease progression
      or other reason. The primary endpoint was 6-month progression-free survival
      (PFS). RESULTS: KRAS, NRAS, or BRAF was mutated in mCRC samples in 60%, 20%, and
      13% of patients, respectively. Median time from initial diagnosis of metastases
      to the start of regorafenib and treatment duration was 13.8 months and 7 weeks,
      respectively. Reasons for discontinuation included disease progression (80%),
      investigator decision (13%), and adverse events (AEs; 7%). Seven patients (47%)
      required dose reduction, mostly for asthenia (43%). The most common regorafenib
      related grade 3 AEs were asthenia (33%), dysphonia (13%), and hypertension (13%)
      (Table 1). There were no grade 4 toxicities. No patient was progression-free at 6
      months. Median PFS, time to progression (TTP), and overall survival (OS) were
      2.2, 2.0, and 3.3 months, respectively. CONCLUSION: Although stopped prematurely
      for failing to accrue, in the population analyzed, regorafenib failed to
      demonstrate clinical activity in KRAS- or BRAF-mutated mCRC with progression
      following first-line with FOLFOXIRI plus bevacizumab, although tolerability was
      acceptable. Our trial suggests that exploring regorafenib efficacy in an earlier
      line of therapy should not be undertaken without better population refinement.

PMID- 30120164
TI  - Clinicopathological and Treatment-Associated Prognostic Factors in Patients with
      Breast Cancer Leptomeningeal Metastases in Relation to Tumor Biology.
AB  - BACKGROUND: Breast cancer (BC) is one of the solid tumors most commonly
      associated with leptomeningeal disease (LMD). LMD carries a devastating
      prognosis; however, disease presentation and prognostic factors are uncertain.
      SUBJECTS, MATERIALS, AND METHODS: In order to describe patient characteristics,
      treatment patterns, and factors associated with survival in a contemporary
      multicentric cohort, 153 consecutive BC patients diagnosed with LMD at two
      European institutions (2002-2017) were included. Time to LMD and overall survival
      (OS) after LMD diagnosis were evaluated using the Kaplan-Meier method and Cox
      proportional hazards models. RESULTS: Median age at LMD diagnosis was 58 years
      (25-84). Tumor phenotype distribution was as follows: hormone receptor (HR)
      positive (HR+)/human epidermal growth receptor 2 (HER2) negative 51.0%, triple
      negative 15.0%, HR+/HER2 positive (HER2+) 13.1% and HR negative/HER2+ 7.2%. Most
      patients received active anticancer treatments (radiation therapy [RT] n = 42,
      systemic therapy n = 110, intrathecal treatment n = 103).Median OS was 3.9 months
      (95% confidence interval [CI] 2.4-5.5). Eastern Cooperative Oncology Group
      performance status (ECOG PS) >2, high white blood cells count, low glucose, and
      high protein in cerebrospinal fluid (CSF) were poor prognostic factors. Having
      received RT or systemic treatment was associated with better prognosis. In
      multivariate analysis, ECOG PS (hazard ratio 2.22, 95% CI 1.25-3.94), CSF glucose
      levels (hazard ratio 1.74, 95% CI 1.05-2.88), and having received systemic
      treatment (hazard ratio 0.17, 95% CI 0.09-0.32) were confirmed as independent
      prognostic factors. In HER2+ BC patients, having received systemic HER2-targeted
      therapy was the only factor maintaining independent prognostication (hazard ratio
      0.12, 95% CI 0.02-0.67) in multivariate analysis. CONCLUSION: Despite being
      limited by their retrospective nature, these results highlight the need for
      clinical trials in BC LMD, stratified on tumor biology. IMPLICATIONS FOR
      PRACTICE: Leptomeningeal disease (LMD) is a devastating complication of breast
      cancer (BC), and its optimal therapy is still not defined. Here, patient
      characteristics, treatment patterns, and prognostic factors from a contemporary
      cohort of 153 BC-related LMD patients are reported. In multivariate analysis,
      Eastern Cooperative Oncology Group performance status, cerebrospinal fluid
      glucose levels, and having received systemic treatment were confirmed as
      independent prognostic factors in the overall population, whereas in human
      epidermal growth receptor 2 (HER2) positive BC patients, having received systemic
      HER2-targeted therapy was the only factor maintaining independent prognostication
      in multivariate analysis. These results highlight the need to consider
      stratification on tumor biology in the treatment of BC LMD.

PMID- 30120165
TI  - Permanent Chemotherapy-Induced Alopecia in Patients with Breast Cancer: A 3-Year
      Prospective Cohort Study.
AB  - BACKGROUND: Although chemotherapy-induced alopecia (CIA) is considered temporary,
      some patients report persistent alopecia several years after chemotherapy. There
      is, however, a paucity of long-term prospective data on the incidence and impact
      of permanent CIA (PCIA). The objective of our study was to estimate the long-term
      incidence of PCIA in a cohort of patients with breast cancer whose hair volume
      and density were measured prior to chemotherapy and who were followed for 3 years
      after chemotherapy. MATERIALS AND METHODS: Prospective cohort study of
      consecutive patients >=18 years of age with postoperative diagnosis of stage I
      III breast cancer expected to receive adjuvant chemotherapy at the outpatient
      breast cancer clinic at the Samsung Medical Center in Seoul, Korea, from February
      2012 to July 2013 (n = 61). Objective hair density and thickness were measured
      using a noninvasive bioengineering device. RESULTS: The proportion of
      participants who had PCIA at 6 months and 3 years was 39.5% and 42.3%,
      respectively. PCIA was characterized in most patients by incomplete hair
      regrowth. Patients who received a taxane-based regimen were more likely to
      experience PCIA compared with patients with other types of chemotherapy. At a 3
      year follow-up, hair thinning was the most common problem reported by study
      participants (75.0%), followed by reduced hair volume (53.9%), hair loss (34.6%),
      and gray hair (34.6%). CONCLUSION: PCIA is a common adverse event of breast
      cancer adjuvant cytotoxic chemotherapy. Clinicians should be aware of this
      distressing adverse event and develop supportive care strategies to counsel
      patients and minimize its impact on quality of life. IMPLICATIONS FOR PRACTICE:
      Knowledge of permanent chemotherapy-induced alopecia, an under-reported adverse
      event, should lead to optimized pretherapy counseling, anticipatory coping
      techniques, and potential therapeutic strategies for this sequela of treatment.

PMID- 30120166
TI  - Prognostic Factors in Patients with Metastatic Breast Cancer with Bone-Only
      Metastases.
AB  - BACKGROUND: Patients with metastatic breast cancer with bone-only metastases
      (BOM) are a unique patient population without consensus regarding high-risk
      characteristics, which we sought to establish. METHODS: We identified 1,445
      patients with BOM followed for at least 6 months at MD Anderson Cancer Center
      from January 1, 1997, to December 31, 2015. RESULTS: Seventy-one percent (n =
      936) of the 1,325 patients with BOM with available pain characterization were
      symptomatic at time of BOM diagnosis. Pain was more common in patients with lytic
      compared with blastic or sclerotic metastases (odds ratio [OR], 1.79; 95%
      confidence interval [CI,] 1.26-2.53) and multiple versus single bone metastases
      (OR, 1.37; 95% CI, 1.03-1.83). Poorer overall survival (OS) was also noted in
      patients with multiple bone metastases (median OS, 4.80 years; 95% CI, 4.49-5.07)
      compared with single bone metastasis (median OS, 7.54 years; 95% CI, 6.28-10.10)
      and in patients with metastases in both the axial and appendicular skeleton
      (median OS, 4.58 years; 95% CI, 4.23-4.96) compared with appendicular-only
      (median OS, 6.78 years; 95% CI, 5.26-7.96) or axial-only metastases (median OS,
      5.62 years; 95% CI, 4.81-6.69). Black/non-Hispanic patients had poorer outcomes,
      and patients aged 40-49 years at time of breast cancer diagnosis had
      significantly better OS compared with both younger and older patient groups.
      CONCLUSION: Overall, several risk features for decreased OS were identified,
      including multiple bone metastases and both axial and appendicular skeleton
      involvement. Multiple bone metastases and lytic bone metastases were associated
      with increased pain. IMPLICATIONS FOR PRACTICE: Patients with metastatic breast
      cancer and bone-only metastases (BOM) represent a poorly characterized patient
      subset. The ability to identify unique patient characteristics at time of BOM
      diagnosis associated with increased morbidity or mortality would allow for
      recognition of patients who would benefit from more aggressive therapy. In this
      study, the largest sample of patients with BOM thus far reported is
      characterized, highlighting several higher-risk BOM groups, including those with
      multiple bone metastases and bone metastases in both the axial and appendicular
      skeleton at time of BOM diagnosis. In addition to tailoring current practices for
      these high-risk patients, ongoing studies of these patients are indicated.

PMID- 30120168
TI  - Safety of Tubal Occlusion by Minilaparotomy Provided by Trained Clinical Officers
      Versus Assistant Medical Officers in Tanzania: A Randomized, Controlled,
      Noninferiority Trial.
AB  - BACKGROUND: Tubal occlusion by minilaparotomy is a safe, highly effective, and
      permanent way to limit childbearing. We aimed to establish whether the safety of
      the procedure provided by trained clinical officers (COs) was not inferior to the
      safety when provided by trained assistant medical officers (AMOs), as measured by
      major adverse event (AE) rates. METHODS: In this randomized, controlled, open
      label noninferiority trial, we enrolled participants at 7 health facilities in
      Arusha region, Tanzania, as well as during outreach activities conducted in
      Arusha and neighboring regions. Consenting, eligible participants were randomly
      allocated by a research assistant at each site to minilaparotomy performed by a
      trained CO or by a trained AMO, in a 1:1 ratio. We asked participants to return
      at 3, 7, and 42 days postsurgery. The primary outcome was the rate of major AEs
      following minilaparotomy performed by COs versus AMOs, during the procedure and
      through 42 days follow-up. The noninferiority margin was 2%. The trial is
      registered with ClinicalTrials.gov, Identifier NCT02944149. RESULTS: We randomly
      allocated 1,970 participants between December 2016 and June 2017, 984 to the CO
      group and 986 to the AMO group. Most (87%) minilaparotomies were conducted during
      outreach services. In the intent-to-treat analysis, 0 of 978 participants had a
      major AE in the CO group compared with 1 (0.1%) of 984 in the AMO group (risk
      difference: -0.1% [95% confidence interval: -0.3% to 0.1%]), meeting the criteria
      for noninferiority. We saw no evidence of differences in measures of procedure
      performance, participant satisfaction, or provider self-efficacy between the
      groups. CONCLUSIONS: Tubal occlusion by minilaparotomy performed by trained COs
      is safe, effective, and acceptable to women, and the procedure can be safely and
      effectively provided in outreach settings. Our results provide evidence to
      support policy change in resource-limited settings to allow task shifting of
      minilaparotomy to properly trained and supported COs, increasing access to female
      sterilization and helping to meet the rising demand for the procedure among women
      wanting to avoid pregnancy. They also suggest high demand for these services in
      Tanzania, given the large number of women recruited in a relatively short time
      period.

PMID- 30120169
TI  - Looking for the positive.

PMID- 30120167
TI  - Glucose Uptake via STP Transporters Inhibits in Vitro Pollen Tube Growth in a
      HEXOKINASE1-Dependent Manner in Arabidopsis thaliana.
AB  - Pollen tube growth requires a high amount of metabolic energy and precise
      targeting toward the ovules. Sugars, especially glucose, can serve as nutrients
      and as signaling molecules. Unexpectedly, in vitro assays revealed an inhibitory
      effect of glucose on pollen tube elongation, contradicting the hypothesis that
      monosaccharide uptake is a source of nutrition for growing pollen tubes.
      Measurements with Forster resonance energy transfer-based nanosensors revealed
      that glucose is taken up into pollen tubes and that the intracellular
      concentration is in the low micromolar range. Pollen tubes of stp4-6-8-9-10-11
      sextuple knockout plants generated by crossings and CRISPR/Cas9 showed only a
      weak response to glucose, indicating that glucose uptake into pollen tubes is
      mediated mainly by these six monosaccharide transporters of the SUGAR TRANSPORT
      PROTEIN (STP) family. Analyses of HEXOKINASE1 (HXK1) showed a strong expression
      of this gene in pollen. Together with the glucose insensitivity and altered semi
      in vivo growth rate of pollen tubes from hxk1 knockout lines, this strongly
      suggests that glucose is an important signaling molecule for pollen tubes, is
      taken up by STPs, and detected by HXK1. Equimolar amounts of fructose abolish the
      inhibitory effect of glucose indicating that only an excess of glucose is
      interpreted as a signal. This provides a possible model for the discrimination of
      signaling and nutritional sugars.

PMID- 30120170
TI  - UK export agreement with Saudi Arabia will see no animals stunned before they are
      slaughtered.

PMID- 30120172
TI  - 'Plausible' risk posed by bovine TB in hounds.

PMID- 30120176
TI  - Investigating a whale mass mortality event.
AB  - In 2016, 30 sperm whales died having stranded in the southern North Sea.
      Researchers have now investigated what caused this. Georgina Mills reports.

PMID- 30120177
TI  - Investigating bovine TB in an expensive alpaca.
AB  - Jessica Li, a fourth year vet student at Cambridge University, spent her EMS
      placement with Vet Record last week. She used part of her time to delve deeper
      into the case of Geronimo, the alpaca which tested positive for bovine TB, and
      the implications for future camelid testing.

PMID- 30120178
TI  - Ovine coccidiosis cases reach eight-year high in Scotland.

PMID- 30120179
TI  - Correction: Inadequate feeding and grazing leads to illthrift and death in cattle
      and sheep.

PMID- 30120180
TI  - Pestivirus infection of sheep - testing times?

PMID- 30120183
TI  - Johne's disease control programmes.

PMID- 30120181
TI  - Serological survey of British sheep flocks for evidence of exposure to ovine
      pestiviruses.
AB  - Ovine pestiviruses have the potential to reduce productivity in the British sheep
      flock. However, their prevalence and impact are currently poorly understood. This
      study aimed to estimate the exposure to pestiviruses in adult breeding ewe stock.
      Blood samples collected for metabolic profiling before lambing were tested using
      an ELISA that detected antibodies raised to both bovine viral diarrhoea virus and
      Border disease virus. A group of 15 animals were tested per flock. A total of 34
      farms were tested, of which 13 had at least one seropositive animal. In those
      positive flocks between one and nine of the animals tested antibody-positive.
      Positive flocks were identified in all regions of Great Britain. This work
      suggests that exposure to ovine pestiviruses is widespread, and that it is timely
      to investigate flock-level prevalence and possible production impacts of endemic
      infection.

PMID- 30120184
TI  - West Nile virus season in Europe.

PMID- 30120185
TI  - Correction: Beavers are back in the Forest of Dean.

PMID- 30120186
TI  - Choosing veganism.

PMID- 30120188
TI  - Why are vets falling out of love with the job?

PMID- 30120189
TI  - Why I think being a vet is still great.

PMID- 30120190
TI  - Veterinary trials and tribulations.
AB  - Dog owner Jodi Ware makes the case for transparency in companion animal research.

PMID- 30120191
TI  - A call for better regulation of veterinary medical devices.
AB  - John Innes discusses the need for greater oversight of the veterinary medical
      devices industry.

PMID- 30120192
TI  - Becoming responsibly selfish.

PMID- 30120197
TI  - Physiological CRAC channel activation and pore properties require STIM1 binding
      to all six Orai1 subunits.
AB  - The binding of STIM1 to Orai1 controls the opening of store-operated CRAC
      channels as well as their extremely high Ca2+ selectivity. Although STIM1 dimers
      are known to bind directly to the cytosolic C termini of the six Orai1 subunits
      (SUs) that form the channel hexamer, the dependence of channel activation and
      selectivity on the number of occupied binding sites is not well understood. Here
      we address these questions using dimeric and hexameric Orai1 concatemers in which
      L273D mutations were introduced to inhibit STIM1 binding to specific Orai1 SUs.
      By measuring FRET between fluorescently labeled STIM1 and Orai1, we find that
      homomeric L273D mutant channels fail to bind STIM1 appreciably; however, the
      L273D SU does bind STIM1 and contribute to channel activation when located
      adjacent to a WT SU. These results suggest that STIM1 dimers can interact with
      pairs of neighboring Orai1 SUs. Surprisingly, a single L273D mutation within the
      Orai1 hexamer reduces channel open probability by ~90%, triples the size of the
      single-channel current, weakens the Ca2+ binding affinity of the selectivity
      filter, and lowers the selectivity for Na+ over Cs+ in the absence of divalent
      cations. These findings reveal a surprisingly strong functional coupling between
      STIM1 binding and CRAC channel gating and pore properties. We conclude that under
      physiological conditions, all six Orai1 SUs of the native CRAC channel bind STIM1
      to effectively open the pore and generate the signature properties of extremely
      low conductance and high ion selectivity.

PMID- 30120200
TI  - Difference between recommended retail price and sales price for tobacco products
      in independent and convenience (small) retailers before and after the
      introduction of standardised tobacco packaging in the UK.
AB  - AIM: Recommended retail price (RRP) is a marketing strategy used by tobacco
      companies to maintain competitiveness, communicate product positioning and drive
      sales. We explored small retailer adherence to RRP before and after the
      introduction of the Standardised Packaging of Tobacco Products Regulations in the
      UK (fully implemented on 20 May 2017) which mandated standardised packaging of
      cigarettes and rolling tobacco, set minimum pack/pouch sizes and prohibited price
      marking. METHOD: Monthly electronic point of sale data from 500 small retailers
      in England, Scotland and Wales were analysed. From May 2016 to October 2017, we
      monitored 20 of the best-selling fully branded tobacco products (15 factory-made
      cigarettes, 5 rolling tobacco) and their standardised equivalents. Adherence to
      RRP was measured as the average difference (%) between monthly RRPs and sales
      prices by pack type (fully branded vs standardised), price-marking on packaging
      and price segment. RESULTS: The average difference between RRP and sales price
      increased from +0.36% above RRP (SD=0.72) in May 2016, when only fully branded
      packs were sold, to +1.37% in October 2017 (SD=0.30), when standardised packs
      were mandatory. Increases above RRP for fully branded packs increased as they
      were phased out, with deviation greater for non-price-marked packs and premium
      products. DISCUSSION: Despite tobacco companies emphasising the importance of
      RRP, small retailers implemented small increases above RRP as standardised
      packaging was introduced. Consequently, any intended price changes by tobacco
      companies in response to the legislation (ie, to increase affordability or brand
      positioning) may be confounded by retailer behaviour, and such deviation may
      increase consumer price sensitivity.

PMID- 30120198
TI  - Biochemical properties and in planta effects of NopM, a rhizobial E3 ubiquitin
      ligase.
AB  - Nodulation outer protein M (NopM) is an IpaH family type three (T3) effector
      secreted by the nitrogen-fixing nodule bacterium Sinorhizobium sp. strain NGR234.
      Previous work indicated that NopM is an E3 ubiquitin ligase required for an
      optimal symbiosis between NGR234 and the host legume Lablab purpureus Here, we
      continued to analyze the function of NopM. Recombinant NopM was biochemically
      characterized using an in vitro ubiquitination system with Arabidopsis thaliana
      proteins. In this assay, NopM forms unanchored polyubiquitin chains and possesses
      auto-ubiquitination activity. In a NopM variant lacking any lysine residues, auto
      ubiquitination was not completely abolished, indicating noncanonical auto
      ubiquitination of the protein. In addition, we could show intermolecular
      ubiquitin transfer from NopM to C338A (enzymatically inactive NopM form) in vitro
      Bimolecular fluorescence complementation analysis provided clues about NopM-NopM
      interactions at plasma membranes in planta NopM, but not C338A, expressed in
      tobacco cells induced cell death, suggesting that E3 ubiquitin ligase activity of
      NopM induced effector-triggered immunity responses. Likewise, expression of NopM
      in Lotus japonicus caused reduced nodule formation, whereas expression of C338A
      showed no obvious effects on symbiosis. Further experiments indicated that serine
      residue 26 of NopM is phosphorylated in planta and that NopM can be
      phosphorylated in vitro by salicylic acid-induced protein kinase (NtSIPK), a
      mitogen-activated protein kinase (MAPK) of tobacco. Hence, NopM is a
      phosphorylated T3 effector that can interact with itself, with ubiquitin, and
      with MAPKs.

PMID- 30120201
TI  - Tax harmonisation and tobacco product prices in the European Union, 2004-2015.
AB  - OBJECTIVES: The European Commission has formally opened a process of revision of
      its tobacco tax directive. The purpose of this study is to analyse the evolution
      of cigarette and roll-your-own (RYO) tobacco prices in order to identify avenues
      for the improvement of public health goals. METHODS: Pooled cross-sectional data
      on prices and taxes on cigarettes and RYO tobacco in the Member States over 2004
      2015 is used to track the distributions of the most popular price category and
      the weighted average price of these products and to relate them to the underlying
      tax structure. RESULTS: The inflation-adjusted prices for the two products have
      increased over the period, but the dispersion of prices across Member States has
      remained constant. Throughout the period, there was a pervasive price gap between
      cigarettes and RYO tobacco within the Member States. Such features are explained
      by the underlying tax design. DISCUSSION: The current tax stance has been
      successful at increasing both cigarette and RYO tobacco prices. To further
      enhance the public health impact of the European Union tax directive, the
      revision should promote the convergence of prices across Member States and aim at
      closing the price gap between cigarettes and RYO tobacco. These objectives call
      for increasing the mandatory minimum levels of excise duty on the two products,
      preferably linking them to the evolution of a European weighted average price.
      The pace of increase should be faster for RYO tobacco in order to close the gap
      with respect to cigarette prices.

PMID- 30120199
TI  - Identification and characterization of ubiquitinylation sites in TAR DNA-binding
      protein of 43 kDa (TDP-43).
AB  - TAR DNA-binding protein of 43 kDa (TDP-43) forms pathological aggregates in
      neurodegenerative diseases, particularly in certain forms of frontotemporal
      dementia and amyotrophic lateral sclerosis. Pathological modifications of TDP-43
      include proteolytic fragmentation, phosphorylation, and ubiquitinylation. A
      pathognomonic TDP-43 C-terminal fragment (CTF) spanning amino acids 193-414
      contains only four lysine residues that could be potentially ubiquitinylated.
      Here, serial mutagenesis of these four lysines to arginine revealed that not a
      single residue is responsible for the ubiquitinylation of mCherry-tagged CTF.
      Removal of all four lysines was necessary to suppress ubiquitinylation.
      Interestingly, Lys-408 substitution enhanced the pathological phosphorylation of
      the immediately adjacent serine residues 409/410 in the context of mCherry-CTF.
      Thus, Lys-408 ubiquitinylation appears to hinder Ser-409/410 phosphorylation in
      TDP-43 CTF. However, we did not observe the same effect for full-length TDP-43.
      We extended the mutagenesis study to full-length TDP-43 and performed MS.
      Ubiquitinylated lysine residues were identified in the nuclear localization
      sequence (NLS; Lys-84 and Lys-95) and RNA-binding region (mostly Lys-160, Lys
      181, and Lys-263). Mutagenesis of Lys-84 confirmed its importance as the major
      determinant for nuclear import, whereas Lys-95 mutagenesis did not significantly
      affect TDP-43's nucleo-cytoplasmic distribution, solubility, aggregation, and RNA
      processing activities. Nevertheless, the K95A mutant had significantly reduced
      Ser-409/410 phosphorylation, emphasizing the suspected interplay between TDP-43
      ubiquitinylation and phosphorylation. Collectively, our analysis of TDP-43
      ubiquitinylation sites indicates that the NLS residues Lys-84 and Lys-95 have
      more prominent roles in TDP-43 function than the more C-terminal lysines and
      suggests a link between specific ubiquitinylation events and pathological TDP-43
      phosphorylation.

PMID- 30120202
TI  - Phaeochromocytoma/paraganglioma and adverse clinical outcomes in patients with
      neurofibromatosis-1.
AB  - INTRODUCTION: Phaeochromocytomas/paragangliomas (PHAEO/PG) are linked to
      hereditary syndromes including neurofibromatosis type 1 (NF-1). Current
      guidelines do not recommend biochemical screening for PHAEO/PG in asymptomatic or
      normotensive patients with NF-1. This strategy may miss preventable morbidities
      in those patients who ultimately present with symptomatic PHAEO/PG. Our aim was
      to review the literature and extract data on mode of presentation and the
      incidence of reported adverse outcomes. METHODS: PubMed and EMBASE literature
      search using the keywords "Phaeochromocytoma", "Paraganglioma" and
      "Neurofibromatosis" was performed looking for reported cases from 2000 to 2018.
      RESULTS: 73 reports of NF-1 patients with PHAEO/PG were found. Patients were
      predominately women (n=40) with a median age of 46 years (range 16-82). PHAEO/PG
      was found incidentally in most patients, 36/73 did not present with typical
      symptoms while 27 patients were normotensive at diagnosis. 31 patients had
      adverse outcomes including metastases and death. CONCLUSION: Given the protean
      presentation of PHAEO/PG, relying on symptomology and blood pressure status as
      triggers for screening is associated with adverse outcomes. Further studies are
      required to ascertain whether biochemical screening in asymptomatic and
      normotensive patients with NF-1 can reduce the rate of adverse outcomes.

PMID- 30120203
TI  - Magnetic resonance T1-mapping evaluates the degree of thyroid destruction in
      patients with autoimmune thyroiditis.
AB  - OBJECTIVE: Autoimmune thyroiditis (AIT) is the most common autoimmune thyroid
      disease. Longitudinal relaxation time mapping (T1-mapping) measured by magnetic
      resonance imaging (MRI) is a new technique for assessing interstitial fibrosis of
      some organs, such as heart and liver. This study aimed to evaluate the
      relationship between T1-mapping value and thyroid function, and determine the
      usefulness of T1-mapping in identifying thyroid destruction in AIT patients.
      METHODS: This case-control study recruited 57 drug-naive AIT patients and 17
      healthy controls. All participants were given thyroid MRI, and T1-mapping values
      were measured using a modified look-locker inversion-recovery sequence. RESULTS:
      AIT patients had significantly higher thyroid T1-mapping values than the healthy
      controls (1,077 +/- 177 vs. 778 +/- 82.9 ms; P < 0.01). A significant increase in
      thyroid T1-mapping values was presented along with the increased severity of
      thyroid dysfunction (P < 0.01). Correlation analyses showed that increased
      thyroid T1-mapping values were associated with higher TSH and lower FT3 and FT4
      levels (TSH: r = 0.75; FT3: r = -0.47; FT4: r = -0.72; all P < 0.01). Receiver
      operating characteristic curve analysis revealed a high diagnostic value of T1
      mapping values for the degree of thyroid destruction (area under the curve was
      0.95, 95%CI: 0.90 - 0.99, P < 0.01). CONCLUSIONS: AIT patients have higher
      thyroid T1-mapping values than the healthy controls, and the T1-mapping values
      increased with the progression of thyroid dysfunction. Thyroid T1-mappingvalue
      might be a new index to quantitatively evaluate the degree of thyroid destruction
      in AIT patients.

PMID- 30120204
TI  - Effects of perioperative tight glycemic control on postoperative outcomes: a meta
      analysis.
AB  - Background The optimal glycemic target during the perioperative period is still
      controversial. We aimed to explore the effects of tight glycemic control (TGC) on
      surgical mortality and morbidity. Methods PubMed, EMBASE and CENTRAL were
      searched from January 1, 1946 to February 28, 2018. Appropriate trails comparing
      the postoperative outcomes (mortality, hypoglycemic events, acute kidney injury,
      etc.) between different levels of TGC and liberal glycemic control were
      identified. Quality assessments were performed with the Jadad scale combined with
      the allocation concealment evaluation. Pooled relative risk (RR) and 95% CI were
      calculated using random effects models. Heterogeneity was detected by the I2
      test. Results Twenty-six trials involving a total of 9315 patients were included
      in the final analysis. The overall mortality did not differ between tight and
      liberal glycemic control (RR, 0.92; 95% CI, 0.78-1.07; I 2 = 20.1%). Among
      subgroup analyses, obvious decreased risks of mortality were found in the short
      term mortality, non-diabetic conditions, cardiac surgery conditions and compared
      to the very liberal glycemic target. Furthermore, TGC was associated with
      decreased risks for acute kidney injury, sepsis, surgical site infection, atrial
      fibrillation and increased risks of hypoglycemia and severe hypoglycemia.
      Conclusions Compared to liberal control, perioperative TGC (the upper level of
      glucose goal <=150 mg/dL) was associated with significant reduction of short-term
      mortality, cardic surgery mortality, non-diabetic patients mortality and some
      postoperative complications. In spite of increased risks of hypoglycemic events,
      perioperative TGC will benefits patients when it is done carefully.

PMID- 30120205
TI  - Rhythm and Synchrony in a Cortical Network Model.
AB  - We studied mechanisms for cortical gamma-band activity in the cerebral cortex and
      identified neurobiological factors that affect such activity. This was done by
      analyzing the behavior of a previously developed, data-driven, large-scale
      network model that simulated many visual functions of monkey V1 cortex (Chariker
      et al., 2016). Gamma activity was an emergent property of the model. The model's
      gamma activity, like that of the real cortex, was (1) episodic, (2) variable in
      frequency and phase, and (3) graded in power with stimulus variables like
      orientation. The spike firing of the model's neuronal population was only
      partially synchronous during multiple firing events (MFEs) that occurred at gamma
      rates. Detailed analysis of the model's MFEs showed that gamma-band activity was
      multidimensional in its sources. Most spikes were evoked by excitatory inputs. A
      large fraction of these inputs came from recurrent excitation within the local
      circuit, but feedforward and feedback excitation also contributed, either through
      direct pulsing or by raising the overall baseline. Inhibition was responsible for
      ending MFEs, but disinhibition led directly to only a small minority of the
      synchronized spikes. As a potential explanation for the wide range of gamma
      characteristics observed in different parts of cortex, we found that the relative
      rise times of AMPA and GABA synaptic conductances have a strong effect on the
      degree of synchrony in gamma.SIGNIFICANCE STATEMENT Canonical computations used
      throughout the cerebral cortex are performed in primary visual cortex (V1).
      Providing theoretical mechanisms for these computations will advance
      understanding of computation throughout cortex. We studied one dynamical feature,
      gamma-band rhythms, in a large-scale, data-driven, computational model of monkey
      V1. Our most significant conclusion is that the sources of gamma band activity
      are multidimensional. A second major finding is that the relative rise times of
      excitatory and inhibitory synaptic potentials have strong effects on spike
      synchrony and peak gamma band power. Insight gained from studying our V1 model
      can shed light on the functions of other cortical regions.

PMID- 30120206
TI  - Medial Auditory Thalamus Is Necessary for Expression of Auditory Trace Eyelid
      Conditioning.
AB  - Transforming a brief sensory event into a persistent neural response represents a
      mechanism for linking temporally disparate stimuli together to support learning.
      The cerebellum requires this type of persistent input during trace conditioning
      to engage associative plasticity and acquire adaptively timed conditioned
      responses (CRs). An initial step toward identifying the sites and mechanisms
      generating and transmitting persistent signals to the cerebellum is to identify
      the input pathway. The medial auditory thalamic nuclei (MATN) are the necessary
      and sufficient source of auditory input to the cerebellum for delay conditioning
      in rodents and a possible input to forebrain sites generating persistent signals.
      Using pharmacological and computational approaches, we test (1) whether the
      necessity of MATN during auditory eyelid conditioning is conserved across
      species, (2) whether the MATN are necessary for the expression of trace eyelid
      CRs, and if so, (3)whether this relates to the generation of persistent signals.
      We find that contralateral inactivation of MATN with muscimol largely abolished
      trace and delay CRs in male rabbits. Residual CRs were decreased in amplitude,
      but CR timing was unaffected. Results from large-scale cerebellar simulations are
      consistent with previous experimental demonstrations that silencing only CS
      duration inputs does not abolish trace CRs, and instead affects their timing.
      Together, these results suggest that the MATN are a necessary component of both
      the direct auditory stimulus pathway to the cerebellum and the pathway generating
      task-essential persistent signals.SIGNIFICANCE STATEMENT Persistent activity is
      required for working memory-dependent tasks, such as trace conditioning, and
      represents a mechanism by which sensory information can be used over time for
      learning and cognition. This neuronal response entails the transformation of a
      discrete sensory-evoked response into a signal that extends beyond the stimulus
      event. Understanding the generation and transmission of this stimulus
      transformation requires identifying the input sources necessary for task
      essential persistent signals. We report that the medial auditory thalamic nuclei
      are required for the expression of auditory trace conditioning and suggest that
      these nuclei are a component of the pathway-generating persistent signals. Our
      study provides a foundation for testing circuit-level mechanisms underlying
      persistent activity in a cerebellar learning model with identified inputs and
      well defined behavioral outputs.

PMID- 30120207
TI  - The Adhesion-GPCR BAI1 Promotes Excitatory Synaptogenesis by Coordinating
      Bidirectional Trans-synaptic Signaling.
AB  - Excitatory synapses are specialized cell-cell contacts located on actin-rich
      dendritic spines that mediate information flow and storage in the brain. The
      postsynaptic adhesion-G protein-coupled receptor (A-GPCR) BAI1 is a critical
      regulator of excitatory synaptogenesis, which functions in part by recruiting the
      Par3-Tiam1 polarity complex to spines, inducing local Rac1 GTPase activation and
      actin cytoskeletal remodeling. However, a detailed mechanistic understanding of
      how BAI1 controls synapse and spine development remains elusive. Here, we confirm
      that BAI1 is required in vivo for hippocampal spine development, and we identify
      three distinct signaling mechanisms mediating BAI1's prosynaptogenic functions.
      Using in utero electroporation to sparsely knock down BAI1 expression in
      hippocampal pyramidal neurons, we show that BAI1 cell-autonomously promotes
      spinogenesis in the developing mouse brain. BAI1 appears to function as a
      receptor at synapses, as its extracellular N-terminal segment is required for
      both its prospinogenic and prosynaptogenic functions. Moreover, BAI1 activation
      with a Stachel-derived peptide, which mimics a tethered agonist motif found in A
      GPCRs, drives synaptic Rac1 activation and subsequent spine and synapse
      development. We also reveal, for the first time, a trans-synaptic function for
      BAI1, demonstrating in a mixed-culture assay that BAI1 induces the clustering of
      presynaptic vesicular glutamate transporter 1 (vGluT1) in contacting axons,
      indicative of presynaptic differentiation. Finally, we show that BAI1 forms a
      receptor complex with the synaptogenic cell-adhesion molecule Neuroligin-1
      (NRLN1) and mediates NRLN1-dependent spine growth and synapse development.
      Together, these findings establish BAI1 as an essential postsynaptic A-GPCR that
      regulates excitatory synaptogenesis by coordinating bidirectional trans-synaptic
      signaling in cooperation with NRLN1.SIGNIFICANCE STATEMENT Adhesion-G protein
      coupled receptors are cell-adhesion receptors with important roles in nervous
      system development, function, and neuropsychiatric disorders. The postsynaptic
      adhesion-G protein-coupled receptor BAI1 is a critical regulator of dendritic
      spine and excitatory synapse development. However, the mechanism by which BAI1
      controls these functions remains unclear. Our study identifies three distinct
      signaling paradigms for BAI1, demonstrating that it mediates forward, reverse,
      and lateral signaling in spines. Activation of BAI1 by a Stachel-dependent
      mechanism induces local Rac1 activation and subsequent
      spinogenesis/synaptogenesis. BAI1 also signals trans-synaptically to promote
      presynaptic differentiation. Furthermore, BAI1 interacts with the postsynaptic
      cell-adhesion molecule Neuroligin-1 (NRLN1) and facilitates NRLN1-dependent spine
      growth and excitatory synaptogenesis. Thus, our findings establish BAI1 as a
      functional synaptogenic receptor that promotes presynaptic and postsynaptic
      development in cooperation with synaptic organizer NRLN1.

PMID- 30120208
TI  - Feedback-Based Learning in Aging: Contributions and Trajectories of Change in
      Striatal and Hippocampal Systems.
AB  - The striatum supports learning from immediate feedback by coding prediction
      errors (PEs), whereas the hippocampus (HC) plays a parallel role in learning from
      delayed feedback. Both regions show evidence of decline in human aging, but
      behavioral research suggests greater decline in HC versus striatal functions. The
      present study included male and female humans and used fMRI to examine younger
      and older adults' brain activation patterns during a learning task with choice
      feedback presented immediately or after a brief delay. Participants then
      completed a surprise memory task that tested their recognition of trial-unique
      feedback stimuli, followed by assessments of postlearning cue preference, outcome
      probability awareness, and willingness to pay. The study yielded three main
      findings. First, behavioral measures indicated similar rates of learning in
      younger and older adults across conditions, but postlearning measures indicated
      impairment in older adults' ability to subsequently apply learning to
      discriminate between cues. Second, PE signals in the striatum were greater for
      immediate versus delayed feedback in both age groups, but PE signals in the HC
      were greater for delayed versus immediate feedback only in younger adults. Third,
      unlike younger adults, older adults failed to exhibit enhanced episodic memory
      for outcome stimuli in the delayed-feedback condition. Together, these findings
      indicate that HC circuits supporting learning and memory decline more than
      striatal circuits in healthy aging, which suggests that declines in HC learning
      signals may be an important predictor of deficits in learning-dependent economic
      decisions among older adults.SIGNIFICANCE STATEMENT The hippocampus (HC) and
      striatum play distinct and critical roles in learning. Substantial research
      suggests that age-related decline in learning supported by the HC outpaces
      decline in learning supported by the striatum; however, such inferences have been
      drawn by comparing performance in tasks with fundamentally different structures.
      The present study overcomes this obstacle by implementing a single fMRI-learning
      paradigm with a subtle variation in feedback timing to examine differential age
      effects on memory supported by the HC and striatum. Our results provide
      converging behavioral and brain-imaging evidence showing that HC circuits
      supporting learning and memory decline more than striatal circuits in healthy
      aging and that declines in HC learning signals may predict early deficits in
      learning-dependent decisions among older adults.

PMID- 30120211
TI  - The Effects of Cholesterol-Derived Oncometabolites on Nuclear Receptor Function
      in Cancer.
AB  - Epidemiologic studies are controversial concerning the roles played by
      cholesterol in cancer risk and development, possibly as it is not cholesterol per
      se that is pathologic in cancers. Indeed, recent data reveal that the cholesterol
      metabolism in cancer cells can generate endogenous oncopromoter metabolites at
      higher levels compared with normal tissues and/or can be deregulated in the
      production of endogenous oncosuppressor metabolites in an opposite way. These
      metabolites are oxysterols, which are cholesterol oxygenation products generated
      by enzymatic and/or autoxidation processes. All these oxysterols are new classes
      of estrogen, glucocorticoid, or liver X nuclear receptor ligands, and their
      protumor action on their cognate receptors could explain some drug resistance,
      while treatment with antitumor metabolites could complement their deficiency in
      cancers and restore their action on their nuclear receptor. Given that
      hypercholesterolemia and high intakes of cholesterol-rich foods or processed
      foods can generate these oxysterols, their importance in cancer risk or
      development in overweight and obese people is to be considered. The discovery of
      these cholesterol-derived metabolites and the identification of the nuclear
      receptors mediating their pro- or antitumor activities are important findings,
      which should have major implications in the diagnosis, prevention, and treatment
      of different cancers and open new areas of research. Cancer Res; 78(17); 4803-8.
      (c)2018 AACR.

PMID- 30120210
TI  - Promoting Scientist-Advocate Collaborations in Cancer Research: Why and How.
AB  - Advocates bring unique and important viewpoints to the cancer research process,
      ensuring that scientific and medical advances are patient-centered and relevant.
      In this article, we discuss the benefits of engaging advocates in cancer research
      and underscore ways in which both the scientific and patient communities can
      facilitate this mutually beneficial collaboration. We discuss how to establish
      and nurture successful scientist-advocate relationships throughout the research
      process. We review opportunities that are available to advocates who want to
      obtain training in the evaluation of cancer research. We also suggest practical
      solutions that can strengthen communication between scientists and advocates,
      such as introducing scientist-advocate interactions at the trainee level.
      Finally, we highlight the essential role social media can play in disseminating
      patient-supported cancer research findings to the patient community and in
      raising awareness of the importance of promoting cancer research. Our perspective
      offers a model that Georgetown Breast Cancer Advocates have found effective and
      which could be one option for those interested in developing productive,
      successful, and sustainable collaborations between advocates and scientists in
      cancer research. Cancer Res; 78(20); 5723-8. (c)2018 AACR.

PMID- 30120209
TI  - Contextual-Dependent Attention Effect on Crowded Orientation Signals in Human
      Visual Cortex.
AB  - A target becomes hard to identify with nearby visual stimuli. This phenomenon,
      known as crowding, places a fundamental limit on conscious perception and object
      recognition. To understand the neural representation of crowded stimuli, we used
      fMRI and a forward encoding model to reconstruct the target-specific feature from
      multivoxel activation patterns evoked by orientation patches. Orientation
      selective response profiles were constructed in V1-V4 for a target embedded in
      different contexts. Subjects of both sexes either directed their attention over
      all the orientation patches or selectively to the target. In the context with a
      weak crowding effect, attending to the target enhanced the orientation
      selectivity of the response profile; such effect increased along the visual
      pathway. In the context with a strong crowding effect, attending to the target
      enhanced the orientation selectivity of the response profile in the earlier
      visual area, but not in V4. The increase and decrease of orientation selectivity
      along the visual hierarchy demonstrate a contextual-dependent attention effect on
      crowded orientation signals: in the context with a weak crowding effect,
      selective attention gradually resolves the target from nearby distractors along
      the hierarchy; in the context with a strong crowding effect, while selective
      attention maintains the target feature in the earlier visual area, its effect
      decreases in the downstream area. Our findings reveal how the human visual system
      represents the target-specific feature at multiple stages under the limit of
      attention selection in a cluttered scene.SIGNIFICANCE STATEMENT Using fMRI and a
      forward encoding model, we reconstructed orientation-selective response profiles
      for a target embedded in crowded contexts. In the context with a weak crowding
      effect, attention gradually resolves the target from nearby distractors along the
      visual hierarchy. In the context with a strong crowding effect, while the feature
      of the target is preserved in the early visual cortex, it degrades in the later
      visual processing stage. The increase and decrease of orientation selectivity
      along the visual hierarchy reveal how the human visual system strikes to present
      the target-specific feature under the limit of attention selection in a cluttered
      scene.

PMID- 30120212
TI  - Does Racial Bias Affect NCI-Funded PIs' Willingness to Mentor Prospective
      Graduate Students?
AB  - Audit studies suggest that racial discrimination disadvantages black individuals
      in educational/professional advancement. We hypothesized that prospective black
      male doctoral students would experience greater disparity in responses when
      seeking access to National Cancer Institute (NCI)-funded principal investigators
      (PI) compared with prospective white males. Primary aim was to explore response
      and acceptance rates for black versus white men seeking cancer research
      mentorship. Identical e-mails were sent to 1,028 randomly selected PIs affiliated
      with 65 NCI-designated cancer centers from "Lamar Washington" (black; n = 515) or
      "Brad Anderson" (white; n = 513). Primary outcomes: (i) responses within one
      week; and (ii) type of response. We used logistic regression to examine effects
      of condition (black/white) on primary outcomes. Approximately 48.3% and 50.0% of
      the sample responded to "Lamar" and "Brad," respectively. For responders, 40.9%
      and 43.7% and "agreed" to meet with Lamar and Brad, respectively. This design did
      not detect bias by PIs against black prospective male students. Cancer Res;
      78(17); 4809-11. (c)2018 AACR.

PMID- 30120213
TI  - Global microarray profiling identified hsa_circ_0064428 as a potential immune
      associated prognosis biomarker for hepatocellular carcinoma.
AB  - BACKGROUND: Increasing evidence has shown that circular RNAs (circRNAs) are
      involved tumourigenesis and metastasis of hepatocellular carcinoma (HCC);
      however, progression about its function in HCC is relatively slow. Here, we aimed
      to investigate whether plasma circRNAs could reflect the tumour-infiltrating
      lymphocytes (TILs) in HCC tumour tissues and serve as prognosis biomarker for
      HCC. METHODS: Tissue samples of patients with HCC were subjected to
      immunohistochemistry staining against CD8 to examine the TILs. Then, we
      investigated the expression profile of circRNAs by microarray between plasma of
      patients with HCC with high TILs and low TILs, and the differentially expressed
      circRNAs were validated with qRT-PCR. Statistical analysis was performed with
      SPSS software and GraphPad Prism. RESULTS: We have demonstrated that patients
      with HCC with high TILs exhibit a significant better overall survival, suggesting
      clinical outcome could be predicted by TILs. Global circRNA microarray between
      plasma of patients with HCC with high TILs and low TILs successfully identified
      six differentially expressed novel circRNAs. Among them, the expression of
      hsa_circ_0064428 was significantly reduced in patients with HCC with high TILs
      but increased in patients with low TILs. Moreover, hsa_circ_0064428 was
      negatively correlated with patient's survival, tumour size and metastasis.
      CONCLUSION: These findings together imply that hsa_circ_0064428 could be
      considered as a potential HCC prognosis biomarker. Future in-depth research is
      required to further illustrate the involvement of hsa_circ_0064428 in HCC
      tumourigenesis and metastasis.

PMID- 30120214
TI  - Homozygous variants in KIAA1549, encoding a ciliary protein, are associated with
      autosomal recessive retinitis pigmentosa.
AB  - BACKGROUND: Retinitis pigmentosa (RP) shows substantial genetic heterogeneity. It
      has been estimated that in approximately 60%-80% of RP cases, the genetic
      diagnosis can be found using whole exome sequencing (WES). In this study, the
      purpose was to identify causative variants in individuals with genetically
      unexplained retinal disease, which included one consanguineous family with two
      affected siblings and one case with RP. METHODS: To identify the genetic defect,
      WES was performed in both probands, and clinical analysis was performed. To
      obtain insight into the function of KIAA1549 in photoreceptors, mRNA expression,
      knockdown and protein localisation studies were performed. RESULTS: Through
      analysis of WES data, based on population allele frequencies, and in silico
      prediction tools, we identified a homozygous missense variant and a homozygous
      frameshift variant in KIAA1549 that segregate in two unrelated families. Kiaa1549
      was found to localise at the connecting cilium of the photoreceptor cells and the
      synapses of the mouse retina. Both variants affect the long transcript of
      KIAA1549, which encodes a 1950 amino acid protein and shows prominent brain
      expression. The shorter transcript encodes a 734 amino acid protein with a high
      retinal expression and is affected by the identified missense variant.
      Strikingly, knockdown of the long transcript also leads to decreased expression
      of the short transcript likely explaining the non-syndromic retinal phenotype
      caused by the two variants targeting different transcripts. CONCLUSION: In
      conclusion, our results underscore the causality of segregating variants in
      KIAA1549 for autosomal recessive RP. Moreover, our data indicate that KIAA1549
      plays a role in photoreceptor function.

PMID- 30120216
TI  - Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have
      an impact on RAB11 in fibroblasts.
AB  - BACKGROUND: The combination of febrile illness-induced encephalopathy and
      rhabdomyolysis has thus far only been described in disorders that affect cellular
      energy status. In the absence of specific metabolic abnormalities, diagnosis can
      be challenging. OBJECTIVE: The objective of this study was to identify and
      characterise pathogenic variants in two individuals from unrelated families, both
      of whom presented clinically with a similar phenotype that included
      neurodevelopmental delay, febrile illness-induced encephalopathy and episodes of
      rhabdomyolysis, followed by developmental arrest, epilepsy and tetraplegia.
      METHODS: Whole exome sequencing was used to identify pathogenic variants in the
      two individuals. Biochemical and cell biological analyses were performed on
      fibroblasts from these individuals and a yeast two-hybrid analysis was used to
      assess protein-protein interactions. RESULTS: Probands shared a homozygous
      TRAPPC2L variant (c.109G>T) resulting in a p.Asp37Tyr missense variant. TRAPPC2L
      is a component of transport protein particle (TRAPP), a group of multisubunit
      complexes that function in membrane traffic and autophagy. Studies in patient
      fibroblasts as well as in a yeast system showed that the p.Asp37Tyr protein was
      present but not functional and resulted in specific membrane trafficking delays.
      The human missense mutation and the analogous mutation in the yeast homologue
      Tca17 ablated the interaction between TRAPPC2L and TRAPPC10/Trs130, a component
      of the TRAPP II complex. Since TRAPP II activates the GTPase RAB11, we examined
      the activation state of this protein and found increased levels of the active
      RAB, correlating with changes in its cellular morphology. CONCLUSIONS: Our study
      implicates a RAB11 pathway in the aetiology of the TRAPPC2L disorder and has
      implications for other TRAPP-related disorders with similar phenotypes.

PMID- 30120217
TI  - Homozygosity for the c.428delG variant in KIAA0586 in a healthy individual:
      implications for molecular testing in patients with Joubert syndrome.
AB  - BACKGROUND: Joubert syndrome (JBTS) is a rare neurodevelopmental disorder with
      marked phenotypic variability and genetic heterogeneity. Homozygous or compound
      heterozygous mutations in the KIAA0586 gene on chromosome 14q23 are known to be
      associated with JBTS-23. The frameshift variant c.428delG is the most frequent
      KIAA0586 variant reported in JBTS-23; yet, homozygosity of this variant was
      observed in two patients with JBTS-23. However, homozygosity of the c.428delG
      variant was recently reported as well in one healthy individual. OBJECTIVE: To
      clarify whether the frameshift variant c.428delG in KIAA0586 is pathogenic in the
      homozygous state. METHODS: Whole-exome sequencing as well as RNA analysis were
      performed. RESULTS: We identified biallelic mutations, including the variant
      c.428delG and a splice site variant c.1413-1G>C, in KIAA0586 in two siblings with
      clinical and MRI features of JBTS. The c.1413-1G>C variant was inherited from the
      healthy father. The c.428delG variant was found in the healthy mother in a
      homozygous state in blood lymphocytes, hair root cells and buccal epithelial
      cells. RNA analysis revealed that the transcript harbouring the c.428delG variant
      was expressed in blood cells from the healthy mother, indicating that transcripts
      harbouring this variant elude the mechanism of nonsense-mediated mRNA decay.
      CONCLUSION: Considering this and the high allele frequency of 0.003117 in the
      gnomAD database, we conclude that c.428delG represents a JBTS disease-causing
      variant only if present in compound heterozygous state with a more severe
      KIAA0586 variant, but not in a homozygous situation.

PMID- 30120218
TI  - The eye cannot see what the mind does not know: female genital mutilation.

PMID- 30120215
TI  - Perturbations of BMP/TGF-beta and VEGF/VEGFR signalling pathways in non-syndromic
      sporadic brain arteriovenous malformations (BAVM).
AB  - BACKGROUND: Brain arteriovenous malformations (BAVM) represent a congenital
      anomaly of the cerebral vessels with a prevalence of 10-18/100 000. BAVM is the
      leading aetiology of intracranial haemorrhage in children. Our objective was to
      identify gene variants potentially contributing to disease and to better define
      the molecular aetiology underlying non-syndromic sporadic BAVM. METHODS: We
      performed whole-exome trio sequencing of 100 unrelated families with a clinically
      uniform BAVM phenotype. Pathogenic variants were then studied in vivo using a
      transgenic zebrafish model. RESULTS: We identified four pathogenic heterozygous
      variants in four patients, including one in the established BAVM-related gene,
      ENG, and three damaging variants in novel candidate genes: PITPNM3, SARS and
      LEMD3, which we then functionally validated in zebrafish. In addition, eight
      likely pathogenic heterozygous variants (TIMP3, SCUBE2, MAP4K4, CDH2, IL17RD,
      PREX2, ZFYVE16 and EGFR) were identified in eight patients, and 16 patients
      carried one or more variants of uncertain significance. Potential oligogenic
      inheritance (MAP4K4 with ENG, RASA1 with TIMP3 and SCUBE2 with ENG) was
      identified in three patients. Regulation of sma- and mad-related proteins (SMADs)
      (involved in bone morphogenic protein (BMP)/transforming growth factor beta (TGF
      beta) signalling) and vascular endothelial growth factor (VEGF)/vascular
      endotheliual growth factor recepter 2 (VEGFR2) binding and activity (affecting
      the VEGF signalling pathway) were the most significantly affected biological
      process involved in the pathogenesis of BAVM. CONCLUSIONS: Our study highlights
      the specific role of BMP/TGF-beta and VEGF/VEGFR signalling in the aetiology of
      BAVM and the efficiency of intensive parallel sequencing in the challenging
      context of genetically heterogeneous paradigm.

PMID- 30120219
TI  - Double Trouble - Severe Hypernatremia Secondary to Central Diabetes Insipidus
      Complicated by Hypercalcemic Nephrogenic Diabetes Insipidus: A Case Report.
AB  - BACKGROUND Patients with malignancies often have electrolyte abnormalities. We
      present a case of a patient with central diabetes insipidus secondary to
      metastatic pituitary invasion complicated by hypercalcemic nephrogenic diabetes
      insipidus. CASE REPORT We present a case of 40-year-old female with a history of
      stage IV breast cancer with skeletal and leptomeningeal metastasis, who was
      admitted with polyuria, polydipsia, and recent onset of confusion. The patient
      was found to have profound hypernatremia and severe hypercalcemia with normal
      parathyroid and vitamin D serum levels. Urine studies showed low urine osmolality
      and high urine output, despite the higher serum osmolality. The patient received
      5% dextrose for rehydration, 1 dose of intravenous (IV) pamidronate, 1 dose of IV
      desmopressin, and 4 days of subcutaneous calcitonin 200 international units Q12H.
      Initially, her urine output in the hospital was in the range of 350-400
      milliliters/hour, which responded well to 1 dose of 1-desamino-8d-arginine
      vasopressin (DDAVP). In the subsequent days, her confusion resolved with
      normalization of serum sodium and calcium, but she died because of the extensive
      malignancy. CONCLUSIONS Our case emphasizes the importance of identification of
      causes and complications of electrolyte abnormalities associated with metastatic
      cancers. These electrolyte abnormalities can be primary or paraneoplastic and
      should be actively pursued and treated in such cases.

PMID- 30120220
TI  - Long Non-Coding RNA HULC Promotes Progression of Bone Neoplasms.
AB  - BACKGROUND Bone neoplasms are common in humans and have high lethality. Recently,
      great progress has been made in understanding the pathophysiological mechanisms,
      but little is known about the molecular and genetic networks involved. MATERIAL
      AND METHODS qRT-PCR assays were conducted to detect the expression levels of
      lncRNA HULC in various cell lines. MTT assay, Transwell assay, and wound-healing
      assay were performed to investigate the proliferation speed, invasion ability,
      and migration ability of each cell line, respectively. Western blot analysis was
      also done to assess the expression level of EMT-related factors. Statistical
      analysis was performed using the t test, Kaplan-Meier method, and log-rank test.
      RESULTS Compared to the human normal bone cell line, we found lncRNA HULC was
      over-expressed in all 6 bone neoplasm cell lines, and we finally chose HT1080 and
      Saos-2 cell lines, which possessed the highest lncRNA HULC expression level, for
      the subsequent studies. We then observed that the expression level of lncRNA HULC
      was negatively correlated with overall survival rate of bone neoplasm patients,
      which means that lncRNA HULC has prognostic value in patients with bone
      neoplasms. Thus, we assessed the influence of lncRNA HULC down-regulation on
      proliferation, invasion, and migration abilities of bone neoplasm cells, and
      found a significant decrease in these abilities. Finally, we found that down
      regulating lncRNA HULC led to decreased expression of EMT-related factors in bone
      neoplasm cells. CONCLUSIONS LncRNA HULC can promote the tumorigenesis of bone
      neoplasms through increasing the proliferation, invasion, and migration abilities
      and the expression level of EMT-related factors.

PMID- 30120221
TI  - Author Correction: The ASIC3/P2X3 cognate receptor is a pain-relevant and ligand
      gated cationic channel.
AB  - The originally published version of this article contained an error in the name
      of the author Flora Goloncser, which was incorrectly given as Flora Goroncser.
      This has now been corrected in both the PDF and HTML versions of the article.

PMID- 30120223
TI  - Epigenetic dysregulation of naive CD4+ T-cell activation genes in childhood food
      allergy.
AB  - Food allergy poses a significant clinical and public health burden affecting 2
      10% of infants. Using integrated DNA methylation and transcriptomic profiling, we
      found that polyclonal activation of naive CD4+ T cells through the T cell
      receptor results in poorer lymphoproliferative responses in children with
      immunoglobulin E (IgE)-mediated food allergy. Reduced expression of cell cycle
      related targets of the E2F and MYC transcription factor networks, and remodeling
      of DNA methylation at metabolic (RPTOR, PIK3D, MAPK1, FOXO1) and inflammatory
      genes (IL1R, IL18RAP, CD82) underpins this suboptimal response. Infants who fail
      to resolve food allergy in later childhood exhibit cumulative increases in
      epigenetic disruption at T cell activation genes and poorer lymphoproliferative
      responses compared to children who resolved food allergy. Our data indicate
      epigenetic dysregulation in the early stages of signal transduction through the T
      cell receptor complex, and likely reflects pathways modified by gene-environment
      interactions in food allergy.

PMID- 30120224
TI  - Author Correction: A mechanism for CO regulation of ion channels.
AB  - The originally published version of this article contained an error in the
      subheading 'Heme is required for CO-dependent channel activation', which was
      incorrectly given as 'Hame is required for CO-dependent channel activation'. This
      has now been corrected in both the PDF and HTML versions of the Article.

PMID- 30120225
TI  - Understanding how excess lead iodide precursor improves halide perovskite solar
      cell performance.
AB  - The presence of excess lead iodide in halide perovskites has been key for
      surpassing 20% photon-to-power conversion efficiency. To achieve even higher
      power conversion efficiencies, it is important to understand the role of remnant
      lead iodide in these perovskites. To that end, we explored the mechanism
      facilitating this effect by identifying the impact of excess lead iodide within
      the perovskite film on charge diffusion length, using electron-beam-induced
      current measurements, and on film formation properties, from grazing-incidence
      wide-angle X-ray scattering and high-resolution transmission electron microscopy.
      Based on our results, we propose that excess lead iodide in the perovskite
      precursors can reduce the halide vacancy concentration and lead to formation of
      azimuthal angle-oriented cubic alpha-perovskite crystals in-between 0 degrees 
      and 90 degrees . We further identify a higher perovskite carrier concentration
      inside the nanostructured titanium dioxide layer than in the capping layer. These
      effects are consistent with enhanced lead iodide-rich perovskite solar cell
      performance and illustrate the role of lead iodide.

PMID- 30120222
TI  - Microbial tryptophan catabolites in health and disease.
AB  - Accumulating evidence implicates metabolites produced by gut microbes as crucial
      mediators of diet-induced host-microbial cross-talk. Here, we review emerging
      data suggesting that microbial tryptophan catabolites resulting from proteolysis
      are influencing host health. These metabolites are suggested to activate the
      immune system through binding to the aryl hydrocarbon receptor (AHR), enhance the
      intestinal epithelial barrier, stimulate gastrointestinal motility, as well as
      secretion of gut hormones, exert anti-inflammatory, anti-oxidative or toxic
      effects in systemic circulation, and putatively modulate gut microbial
      composition. Tryptophan catabolites thus affect various physiological processes
      and may contribute to intestinal and systemic homeostasis in health and disease.

PMID- 30120227
TI  - Z-FL-COCHO, a cathepsin S inhibitor, enhances oxaliplatin-mediated apoptosis
      through the induction of endoplasmic reticulum stress.
AB  - Multiple cancer cells highly express cathepsin S, which has pro-tumoral effects.
      However, it was previously unknown whether knockdown or a pharmacological
      inhibitor (ZFL) of cathepsin S acts as an inducer of ER stress. Here, ZFL and
      knockdown of cathepsin S markedly induced ER stress through the up-regulation of
      calcium levels in the cytosol. Induction of calcium levels by inhibition of
      cathepsin S is markedly blocked by an inhibitor of the IP3 receptor and the
      ryanodine receptor Ca2+ channel in the ER, but an inhibitor of a mitochondrial
      Ca2+ uniporter had no effect on ZFL-induced calcium levels. Furthermore,
      production of mitochondrial ROS by ZFL was associated with an increase in
      cytosolic calcium levels. ZFL-mediated ER stress enhanced anti-cancer drug
      induced apoptotic cell death, and pretreatment with chemical chaperones or down
      regulation of ATF4 and CHOP by small interfering RNA markedly reduced ZFL plus
      oxaliplatin-induced apoptosis. Taken together, our findings reveal that
      inhibition of cathepsin S is an inducer of ER stress; these findings may
      contribute to the enhancement of therapeutic efficiency in cancer cells.

PMID- 30120226
TI  - The therapeutic significance of mutational signatures from DNA repair deficiency
      in cancer.
AB  - Cancer is fundamentally a disease of the genome and inherited deficiencies in DNA
      repair pathways are well established to increase lifetime cancer risk.
      Computational analysis of pan-cancer data has identified signatures of mutational
      processes thought to be responsible for the pattern of mutations in any given
      cancer. These analyses identified altered DNA repair pathways in a much broader
      spectrum of cancers than previously appreciated with significant therapeutic
      implications. The development of DNA repair deficiency biomarkers is critical to
      the implementation of therapeutic targeting of repair-deficient tumors, using
      either DNA damaging agents or immunotherapy for the personalization of cancer
      therapy.

PMID- 30120229
TI  - Smooth tracking of visual targets distinguishes lucid REM sleep dreaming and
      waking perception from imagination.
AB  - Humans are typically unable to engage in sustained smooth pursuit for imagined
      objects. However, it is unknown to what extent smooth tracking occurs for visual
      imagery during REM sleep dreaming. Here we examine smooth pursuit eye movements
      during tracking of a slow-moving visual target during lucid dreams in REM sleep.
      Highly similar smooth pursuit tracking was observed during both waking perception
      and lucid REM sleep dreaming, in contrast to the characteristically saccadic
      tracking observed during visuomotor imagination. Our findings suggest that, in
      this respect, the visual imagery that occurs during REM sleep is more similar to
      perception than imagination. The data also show that the neural circuitry of
      smooth pursuit can be driven by a visual percept in the absence of retinal
      stimulation and that specific voluntary shifts in the direction of experienced
      gaze within REM sleep dreams are accompanied by corresponding rotations of the
      physical eyes.

PMID- 30120228
TI  - Extension of the crRNA enhances Cpf1 gene editing in vitro and in vivo.
AB  - Engineering of the Cpf1 crRNA has the potential to enhance its gene editing
      efficiency and non-viral delivery to cells. Here, we demonstrate that extending
      the length of its crRNA at the 5' end can enhance the gene editing efficiency of
      Cpf1 both in cells and in vivo. Extending the 5' end of the crRNA enhances the
      gene editing efficiency of the Cpf1 RNP to induce non-homologous end-joining and
      homology-directed repair using electroporation in cells. Additionally, chemical
      modifications on the extended 5' end of the crRNA result in enhanced serum
      stability. Also, extending the 5' end of the crRNA by 59 nucleotides increases
      the delivery efficiency of Cpf1 RNP in cells and in vivo cationic delivery
      vehicles including polymer nanoparticle. Thus, 5' extension and chemical
      modification of the Cpf1 crRNA is an effective method for enhancing the gene
      editing efficiency of Cpf1 and its delivery in vivo.

PMID- 30120230
TI  - Selective N-terminal acylation of peptides and proteins with a Gly-His tag
      sequence.
AB  - Methods for site-selective chemistry on proteins are in high demand for the
      synthesis of chemically modified biopharmaceuticals, as well as for applications
      in chemical biology, biosensors and more. Inadvertent N-terminal gluconoylation
      has been reported during expression of proteins with an N-terminal His tag. Here
      we report the development of this side-reaction into a general method for highly
      selective N-terminal acylation of proteins to introduce functional groups. We
      identify an optimized N-terminal sequence, GHHHn- for the reaction with
      gluconolactone and 4-methoxyphenyl esters as acylating agents, facilitating the
      introduction of functionalities in a highly selective and efficient manner.
      Azides, biotin or a fluorophore are introduced at the N-termini of four unrelated
      proteins by effective and selective acylation with the 4-methoxyphenyl esters.
      This Gly-Hisn tag adds the unique capability for highly selective N-terminal
      chemical acylation of expressed proteins. We anticipate that it can find wide
      application in chemical biology and for biopharmaceuticals.

PMID- 30120231
TI  - Multiple domains of bacterial and human Lon proteases define substrate
      selectivity.
AB  - The Lon protease selectively degrades abnormal proteins or certain normal
      proteins in response to environmental and cellular conditions in many prokaryotic
      and eukaryotic organisms. However, the mechanism(s) behind the substrate
      selection of normal proteins remains largely unknown. In this study, we
      identified 10 new substrates of F. tularensis Lon from a total of 21 candidate
      substrates identified in our previous work, the largest number of novel Lon
      substrates from a single study. Cross-species degradation of these and other
      known Lon substrates revealed that human Lon is unable to degrade many bacterial
      Lon substrates, suggestive of a "organism-adapted" substrate selection mechanism
      for the natural Lon variants. However, individually replacing the N, A, and P
      domains of human Lon with the counterparts of bacterial Lon did not enable the
      human protease to degrade the same bacterial Lon substrates. This result showed
      that the "organism-adapted" substrate selection depends on multiple domains of
      the Lon proteases. Further in vitro proteolysis and mass spectrometry analysis
      revealed a similar substrate cleavage pattern between the bacterial and human Lon
      variants, which was exemplified by predominant representation of leucine,
      alanine, and other hydrophobic amino acids at the P(-1) site within the
      substrates. These observations suggest that the Lon proteases select their
      substrates at least in part by fine structural matching with the proteins in the
      same organisms.

PMID- 30120233
TI  - mTOR-dependent phosphorylation controls TFEB nuclear export.
AB  - During starvation the transcriptional activation of catabolic processes is
      induced by the nuclear translocation and consequent activation of transcription
      factor EB (TFEB), a master modulator of autophagy and lysosomal biogenesis.
      However, how TFEB is inactivated upon nutrient refeeding is currently unknown.
      Here we show that TFEB subcellular localization is dynamically controlled by its
      continuous shuttling between the cytosol and the nucleus, with the nuclear export
      representing a limiting step. TFEB nuclear export is mediated by CRM1 and is
      modulated by nutrient availability via mTOR-dependent hierarchical multisite
      phosphorylation of serines S142 and S138, which are localized in proximity of a
      nuclear export signal (NES). Our data on TFEB nucleo-cytoplasmic shuttling
      suggest an unpredicted role of mTOR in nuclear export.

PMID- 30120232
TI  - SUMOylation of VEGFR2 regulates its intracellular trafficking and pathological
      angiogenesis.
AB  - Regulation of VEGFR2 represents an important mechanism for the control of
      angiogenesis. VEGFR2 activity can be regulated by post-translational
      modifications such as ubiquitination and acetylation. However, whether VEGFR2 can
      be regulated by SUMOylation has not been investigated. Here we show that
      endothelial-specific deletion of the SUMO endopeptidase SENP1 reduces
      pathological angiogenesis and tissue repair during hindlimb ischemia, and VEGF
      induced angiogenesis in the cornea, retina, and ear. SENP1-deficient endothelial
      cells show increased SUMOylation of VEGFR2 and impaired VEGFR2 signalling.
      SUMOylation at lysine 1270 retains VEGFR2 in the Golgi and reduces its surface
      expression, attenuating VEGFR2-dependent signalling. Moreover, we find that SENP1
      is downregulated and VEGFR2 hyper-SUMOylated in diabetic settings and that
      expression of a non-SUMOylated form of VEGFR2 rescues angiogenic defects in
      diabetic mice. These results show that VEGFR2 is regulated by deSUMOylation
      during pathological angiogenesis, and propose SENP1 as a potential therapeutic
      target for the treatment of diabetes-associated angiogenesis.

PMID- 30120234
TI  - Galectin-9 suppresses B cell receptor signaling and is regulated by I-branching
      of N-glycans.
AB  - Leukocytes are coated with a layer of heterogeneous carbohydrates (glycans) that
      modulate immune function, in part by governing specific interactions with glycan
      binding proteins (lectins). Although nearly all membrane proteins bear glycans,
      the identity and function of most of these sugars on leukocytes remain
      unexplored. Here, we characterize the N-glycan repertoire (N-glycome) of human
      tonsillar B cells. We observe that naive and memory B cells express an N-glycan
      repertoire conferring strong binding to the immunoregulatory lectin galectin-9
      (Gal-9). Germinal center B cells, by contrast, show sharply diminished binding to
      Gal-9 due to upregulation of I-branched N-glycans, catalyzed by the beta1,6-N
      acetylglucosaminyltransferase GCNT2. Functionally, we find that Gal-9 is
      autologously produced by naive B cells, binds CD45, suppresses calcium signaling
      via a Lyn-CD22-SHP-1 dependent mechanism, and blunts B cell activation. Thus, our
      findings suggest Gal-9 intrinsically regulates B cell activation and may
      differentially modulate BCR signaling at steady state and within germinal
      centers.

PMID- 30120235
TI  - Galectin-9 binds IgM-BCR to regulate B cell signaling.
AB  - The galectin family of secreted lectins have emerged as important regulators of
      immune cell function; however, their role in B-cell responses is poorly
      understood. Here we identify IgM-BCR as a ligand for galectin-9. Furthermore, we
      show enhanced BCR microcluster formation and signaling in galectin-9-deficient B
      cells. Notably, treatment with exogenous recombinant galectin-9 nearly completely
      abolishes BCR signaling. We investigated the molecular mechanism for galectin-9
      mediated inhibition of BCR signaling using super-resolution imaging and single
      particle tracking. We show that galectin-9 merges pre-existing nanoclusters of
      IgM-BCR, immobilizes IgM-BCR, and relocalizes IgM-BCR together with the
      inhibitory molecules CD45 and CD22. In resting naive cells, we use dual-color
      super-resolution imaging to demonstrate that galectin-9 mediates the close
      association of IgM and CD22, and propose that the loss of this association
      provides a mechanism for enhanced activation of galectin-9-deficient B cells.

PMID- 30120237
TI  - Element- and momentum-resolved electronic structure of the dilute magnetic
      semiconductor manganese doped gallium arsenide.
AB  - The dilute magnetic semiconductors have promise in spin-based electronics
      applications due to their potential for ferromagnetic order at room temperature,
      and various unique switching and spin-dependent conductivity properties. However,
      the precise mechanism by which the transition-metal doping produces
      ferromagnetism has been controversial. Here we have studied a dilute magnetic
      semiconductor (5% manganese-doped gallium arsenide) with Bragg-reflection
      standing-wave hard X-ray angle-resolved photoemission spectroscopy, and resolved
      its electronic structure into element- and momentum- resolved components. The
      measured valence band intensities have been projected into element-resolved
      components using analogous energy scans of Ga 3d, Mn 2p, and As 3d core levels,
      with results in excellent agreement with element-projected Bloch spectral
      functions and clarification of the electronic structure of this prototypical
      material. This technique should be broadly applicable to other multi-element
      materials.

PMID- 30120236
TI  - Early selection of bZIP73 facilitated adaptation of japonica rice to cold
      climates.
AB  - Cold stress is a major factor limiting production and geographic distribution of
      rice (Oryza sativa). Although the growth range of japonica subspecies has
      expanded northward compared to modern wild rice (O. rufipogon), the molecular
      basis of the adaptation remains unclear. Here we report bZIP73, a bZIP
      transcription factor-coding gene with only one functional polymorphism (+511 G>A)
      between the two subspecies japonica and indica, may have facilitated japonica
      adaptation to cold climates. We show the japonica version of bZIP73 (bZIP73Jap)
      interacts with bZIP71 and modulates ABA levels and ROS homeostasis. Evolutionary
      and population genetic analyses suggest bZIP73 has undergone balancing selection;
      the bZIP73Jap allele has firstly selected from standing variations in wild rice
      and likely facilitated cold climate adaptation during initial japonica
      domestication, while the indica allele bZIP73Ind was subsequently selected for
      reasons that remain unclear. Our findings reveal early selection of bZIP73Jap may
      have facilitated climate adaptation of primitive rice germplasms.

PMID- 30120238
TI  - Conditional control of fluorescent protein degradation by an auxin-dependent
      nanobody.
AB  - The conditional and reversible depletion of proteins by auxin-mediated
      degradation is a powerful tool to investigate protein functions in cells and
      whole organisms. However, its wider applications require fusing the auxin
      inducible degron (AID) to individual target proteins. Thus, establishing the
      auxin system for multiple proteins can be challenging. Another approach for
      directed protein degradation are anti-GFP nanobodies, which can be applied to GFP
      stock collections that are readily available in different experimental models.
      Here, we combine the advantages of auxin and nanobody-based degradation
      technologies creating an AID-nanobody to degrade GFP-tagged proteins at different
      cellular structures in a conditional and reversible manner in human cells. We
      demonstrate efficient and reversible inactivation of the anaphase promoting
      complex/cyclosome (APC/C) and thus provide new means to study the functions of
      this essential ubiquitin E3 ligase. Further, we establish auxin degradation in a
      vertebrate model organism by employing AID-nanobodies in zebrafish.

PMID- 30120241
TI  - Author Correction: Bisphosphonate enhances TRAIL sensitivity to human
      osteosarcoma cells via death receptor 5 upregulation.
AB  - After publication of this article, the authors noticed an error in the figure
      section.

PMID- 30120239
TI  - Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high
      throughput mutagenesis.
AB  - Mutations causing aberrant splicing are frequently implicated in human diseases
      including cancer. Here, we establish a high-throughput screen of randomly mutated
      minigenes to decode the cis-regulatory landscape that determines alternative
      splicing of exon 11 in the proto-oncogene MST1R (RON). Mathematical modelling of
      splicing kinetics enables us to identify more than 1000 mutations affecting RON
      exon 11 skipping, which corresponds to the pathological isoform RON?165.
      Importantly, the effects correlate with RON alternative splicing in cancer
      patients bearing the same mutations. Moreover, we highlight heterogeneous nuclear
      ribonucleoprotein H (HNRNPH) as a key regulator of RON splicing in healthy
      tissues and cancer. Using iCLIP and synergy analysis, we pinpoint the
      functionally most relevant HNRNPH binding sites and demonstrate how cooperative
      HNRNPH binding facilitates a splicing switch of RON exon 11. Our results thereby
      offer insights into splicing regulation and the impact of mutations on
      alternative splicing in cancer.

PMID- 30120240
TI  - Ultrafast and highly sensitive infrared photodetectors based on two-dimensional
      oxyselenide crystals.
AB  - Infrared light detection and sensing is deeply embedded in modern technology and
      human society and its development has always been benefitting from the discovery
      of various photoelectric materials. The rise of two-dimensional materials, thanks
      to their distinct electronic structures, extreme dimensional confinement and
      strong light-matter interactions, provides a material platform for next
      generation infrared photodetection. Ideal infrared detectors should have fast
      respond, high sensitivity and air-stability, which are rare to meet at the same
      time in one two-dimensional material. Herein we demonstrate an infrared
      photodetector based on two-dimensional Bi2O2Se crystal, whose main
      characteristics are outstanding in the whole two-dimensional family: high
      sensitivity of 65 AW-1 at 1200 nm and ultrafast photoresponse of ~1 ps at room
      temperature, implying an intrinsic material-limited bandwidth up to 500 GHz. Such
      great performance is attributed to the suitable electronic bandgap and high
      carrier mobility of two-dimensional oxyselenide.

PMID- 30120243
TI  - Divergent global-scale temperature effects from identical aerosols emitted in
      different regions.
AB  - The distribution of anthropogenic aerosols' climate effects depends on the
      geographic distribution of the aerosols themselves. Yet many scientific and
      policy discussions ignore the role of emission location when evaluating aerosols'
      climate impacts. Here, we present new climate model results demonstrating
      divergent climate responses to a fixed amount and composition of aerosol
      emulating China's present-day emissions-emitted from 8 key geopolitical regions.
      The aerosols' global-mean cooling effect is fourteen times greater when emitted
      from the highest impact emitting region (Western Europe) than from the lowest
      (India). Further, radiative forcing, a widely used climate response proxy, fails
      as an effective predictor of global-mean cooling for national-scale aerosol
      emissions in our simulations; global-mean forcing-to-cooling efficacy differs
      fivefold depending on emitting region. This suggests that climate accounting
      should differentiate between aerosols emitted from different countries and that
      aerosol emissions' evolving geographic distribution will impact the global-scale
      magnitude and spatial distribution of climate change.

PMID- 30120242
TI  - Multi-photon near-infrared emission saturation nanoscopy using upconversion
      nanoparticles.
AB  - Multiphoton fluorescence microscopy (MPM), using near infrared excitation light,
      provides increased penetration depth, decreased detection background, and reduced
      phototoxicity. Using stimulated emission depletion (STED) approach, MPM can
      bypass the diffraction limitation, but it requires both spatial alignment and
      temporal synchronization of high power (femtosecond) lasers, which is limited by
      the inefficiency of the probes. Here, we report that upconversion nanoparticles
      (UCNPs) can unlock a new mode of near-infrared emission saturation (NIRES)
      nanoscopy for deep tissue super-resolution imaging with excitation intensity
      several orders of magnitude lower than that required by conventional MPM dyes.
      Using a doughnut beam excitation from a 980 nm diode laser and detecting at 800
      nm, we achieve a resolution of sub 50 nm, 1/20th of the excitation wavelength, in
      imaging of single UCNP through 93 MUm thick liver tissue. This method offers a
      simple solution for deep tissue super resolution imaging and single molecule
      tracking.

PMID- 30120244
TI  - Linear mapping approximation of gene regulatory networks with stochastic
      dynamics.
AB  - The presence of protein-DNA binding reactions often leads to analytically
      intractable models of stochastic gene expression. Here we present the linear
      mapping approximation that maps systems with protein-promoter interactions onto
      approximately equivalent systems with no binding reactions. This is achieved by
      the marriage of conditional mean-field approximation and the Magnus expansion,
      leading to analytic or semi-analytic expressions for the approximate time
      dependent and steady-state protein number distributions. Stochastic simulations
      verify the method's accuracy in capturing the changes in the protein number
      distributions with time for a wide variety of networks displaying auto- and
      mutual-regulation of gene expression and independently of the ratios of the
      timescales governing the dynamics. The method is also used to study the first
      passage time distribution of promoter switching, the sensitivity of the size of
      protein number fluctuations to parameter perturbation and the stochastic
      bifurcation diagram characterizing the onset of multimodality in protein number
      distributions.

PMID- 30120245
TI  - Cell-penetrating artificial mitochondria-targeting peptide-conjugated
      metallothionein 1A alleviates mitochondrial damage in Parkinson's disease models.
AB  - An excess of reactive oxygen species (ROS) relative to the antioxidant capacity
      causes oxidative stress, which plays a role in the development of Parkinson's
      disease (PD). Because mitochondria are both sites of ROS generation and targets
      of ROS damage, the delivery of antioxidants to mitochondria might prevent or
      alleviate PD. To transduce the antioxidant protein human metallothionein 1A
      (hMT1A) into mitochondria, we computationally designed a cell-penetrating
      artificial mitochondria-targeting peptide (CAMP). The recombinant CAMP-conjugated
      hMT1A fusion protein (CAMP-hMT1A) successfully localized to the mitochondria.
      Treating a cell culture model of PD with CAMP-hMT1A restored tyrosine hydroxylase
      expression and mitochondrial activity and reduced ROS production. Furthermore,
      injection of CAMP-hMT1A into the brain of a mouse model of PD rescued movement
      impairment and dopaminergic neuronal degeneration. CAMP-hMT1A delivery into
      mitochondria might be therapeutic against PD by alleviating mitochondrial damage,
      and we predict that CAMP could be used to deliver other cargo proteins to the
      mitochondria.

PMID- 30120246
TI  - The tumor suppressor menin prevents effector CD8 T-cell dysfunction by targeting
      mTORC1-dependent metabolic activation.
AB  - While menin plays an important role in preventing T-cell dysfunction, such as
      senescence and exhaustion, the regulatory mechanisms remain unclear. We found
      that menin prevents the induction of dysfunction in activated CD8 T cells by
      restricting the cellular metabolism. mTOR complex 1 (mTORC1) signaling,
      glycolysis, and glutaminolysis are augmented by menin deficiency. Rapamycin
      treatment prevents CD8 T-cell dysfunction in menin-deficient CD8 T cells. Limited
      glutamine availability also prevents CD8 T-cell dysfunction induced by menin
      deficiency, and its inhibitory effect is antagonized by alpha-ketoglutarate
      (alpha-KG), an intermediate metabolite of glutaminolysis. alpha-KG-dependent
      histone H3K27 demethylation seems to be involved in the dysfunction in menin
      deficient CD8 T cells. We also found that alpha-KG activates mTORC1-dependent
      central carbon metabolism. These findings suggest that menin maintains the T-cell
      functions by limiting mTORC 1 activity and subsequent cellular metabolism.

PMID- 30120247
TI  - An intrinsic tumour eviction mechanism in Drosophila mediated by steroid hormone
      signalling.
AB  - Polycomb group proteins are epigenetic regulators maintaining transcriptional
      memory during cellular proliferation. In Drosophila larvae, malfunction of
      Polyhomeotic (Ph), a member of the PRC1 silencing complex, results in neoplastic
      growth. Here, we report an intrinsic tumour suppression mechanism mediated by the
      steroid hormone ecdysone during metamorphosis. Ecdysone alters neoplastic growth
      into a nontumorigenic state of the mutant ph cells which then become eliminated
      during adult stage. We demonstrate that ecdysone exerts this function by inducing
      a heterochronic network encompassing the activation of the microRNA lethal-7,
      which suppresses its target gene chronologically inappropriate morphogenesis.
      This pathway can also promote remission of brain tumours formed in brain tumour
      mutants, revealing a restraining of neoplastic growth in different tumour types.
      Given the conserved role of let-7, the identification and molecular
      characterization of this innate tumour eviction mechanism in flies might provide
      important clues towards the exploitation of related pathways for human tumour
      therapy.

PMID- 30120248
TI  - Insights into degradation mechanism of N-end rule substrates by p62/SQSTM1
      autophagy adapter.
AB  - p62/SQSTM1 is the key autophagy adapter protein and the hub of multi-cellular
      signaling. It was recently reported that autophagy and N-end rule pathways are
      linked via p62. However, the exact recognition mode of degrading substrates and
      regulation of p62 in the autophagic pathway remain unknown. Here, we present the
      complex structures between the ZZ-domain of p62 and various type-1 and type-2 N
      degrons. The binding mode employed in the interaction of the ZZ-domain with N
      degrons differs from that employed by classic N-recognins. It was also determined
      that oligomerization via the PB1 domain can control functional affinity to the R
      BiP substrate. Unexpectedly, we found that self-oligomerization and disassembly
      of p62 are pH-dependent. These findings broaden our understanding of the
      functional repertoire of the N-end rule pathway and provide an insight into the
      regulation of p62 during the autophagic pathway.

PMID- 30120249
TI  - Axoneme polyglutamylation regulated by Joubert syndrome protein ARL13B controls
      ciliary targeting of signaling molecules.
AB  - Tubulin polyglutamylation is a predominant axonemal post-translational
      modification. However, if and how axoneme polyglutamylation is essential for
      primary cilia and contribute to ciliopathies are unknown. Here, we report that
      Joubert syndrome protein ARL13B controls axoneme polyglutamylation, which is
      marginally required for cilia stability but essential for cilia signaling. ARL13B
      interacts with RAB11 effector FIP5 to promote cilia import of glutamylase TTLL5
      and TTLL6. Hypoglutamylation caused by a deficient ARL13B-RAB11-FIP5 trafficking
      pathway shows no effect on ciliogenesis, but promotes cilia disassembly and,
      importantly, impairs cilia signaling by disrupting the proper anchoring of
      sensory receptors and trafficking of signaling molecules. Remarkably, depletion
      of deglutamylase CCP5, the predominant cilia deglutamylase, effectively restores
      hypoglutamylation-induced cilia defects. Our study reveals a paradigm that
      tubulin polyglutamylation is a major contributor for cilia signaling and suggests
      a potential therapeutic strategy by targeting polyglutamylation machinery to
      promote ciliary targeting of signaling machineries and correct signaling defects
      in ciliopathies.

PMID- 30120250
TI  - Mathematical modelling of the impact of expanding levels of malaria control
      interventions on Plasmodium vivax.
AB  - Plasmodium vivax poses unique challenges for malaria control and elimination,
      notably the potential for relapses to maintain transmission in the face of drug
      based treatment and vector control strategies. We developed an individual-based
      mathematical model of P. vivax transmission calibrated to epidemiological data
      from Papua New Guinea (PNG). In many settings in PNG, increasing bed net coverage
      is predicted to reduce transmission to less than 0.1% prevalence by light
      microscopy, however there is substantial risk of rebounds in transmission if
      interventions are removed prematurely. In several high transmission settings,
      model simulations predict that combinations of existing interventions are not
      sufficient to interrupt P. vivax transmission. This analysis highlights the
      potential options for the future of P. vivax control: maintaining existing public
      health gains by keeping transmission suppressed through indefinite distribution
      of interventions; or continued development of strategies based on existing and
      new interventions to push for further reduction and towards elimination.

PMID- 30120251
TI  - Emerging many-body effects in semiconductor artificial graphene with low
      disorder.
AB  - The interplay between electron-electron interactions and the honeycomb topology
      is expected to produce exotic quantum phenomena and find applications in advanced
      devices. Semiconductor-based artificial graphene (AG) is an ideal system for
      these studies that combines high-mobility electron gases with AG topology.
      However, to date, low-disorder conditions that reveal the interplay of electron
      electron interaction with AG symmetry have not been achieved. Here, we report the
      creation of low-disorder AG that preserves the near-perfection of the pristine
      electron layer by fabricating small period triangular antidot lattices on high
      quality quantum wells. Resonant inelastic light scattering spectra show
      collective spin-exciton modes at the M-point's nearly flatband saddle-point
      singularity in the density of states. The observed Coulomb exchange interaction
      energies are comparable to the gap of Dirac bands at the M-point, demonstrating
      interplay between quasiparticle interactions and the AG potential. The saddle
      point exciton energies are in the terahertz range, making low-disorder AG
      suitable for contemporary optoelectronic applications.

PMID- 30120252
TI  - The Arp8 and Arp4 module acts as a DNA sensor controlling INO80 chromatin
      remodeling.
AB  - Nuclear actin and actin-related proteins (Arps) are key components of chromatin
      remodeling and modifying complexes. Although Arps are essential for the functions
      of chromatin remodelers, their specific roles and mechanisms are unclear. Here we
      define the nucleosome binding interfaces and functions of the evolutionarily
      conserved Arps in the yeast INO80 chromatin remodeling complex. We show that the
      N-terminus of Arp8, C-terminus of Arp4 and the HSA domain of Ino80 bind
      extranucleosomal DNA 37-51 base pairs from the edge of nucleosomes and function
      as a DNA-length sensor that regulates nucleosome sliding by INO80. Disruption of
      Arp8 and Arp4 binding to DNA uncouples ATP hydrolysis from nucleosome
      mobilization by disengaging Arp5 from the acidic patch on histone H2A-H2B and the
      Ino80-ATPase domain from the Super-helical Location (SHL) -6 of nucleosomes. Our
      data suggest a functional interplay between INO80's Arp8-Arp4-actin and Arp5
      modules in sensing the DNA length separating nucleosomes and regulating
      nucleosome positioning.

PMID- 30120253
TI  - Finding hens in a haystack: Consistency of movement patterns within and across
      individual laying hens maintained in large groups.
AB  - We sought to objectively quantify and compare the recorded movement and location
      patterns of laying hens within a commercial system. Using a custom tracking
      system, we monitored the location within five zones of a commercial aviary for 13
      hens within a flock of 225 animals for a contiguous period of 11 days. Most hens
      manifested a hen-specific pattern that was (visually) highly consistent across
      days, though, within that consistency, manifested stark differences between hens.
      Three different methods were used to classify individual daily datasets into
      groups based on their similarity: (i) Linear Discriminant Analysis based on six
      summary variables (transitions into each zone) and total transitions; (ii)
      Hierarchical Clustering, a naive clustering analysis technique, applied to
      summary variables and iii) Hierarchical Clustering applied to dissimilarity
      matrices produced by Dynamic Time Warping. The three methods correctly classified
      more than 85% of the hen days and provided a unique means to assess behaviour of
      a system indicating a considerable degree of complexity and structure. We believe
      the current effort is the first to document these location and movement patterns
      within a large, complex commercial system with a large potential to influence the
      assessment of animal welfare, health, and productivity.

PMID- 30120254
TI  - Coupled Transmembrane Substrate Docking and Helical Unwinding in Intramembrane
      Proteolysis of Amyloid Precursor Protein.
AB  - Intramembrane-cleaving proteases (I-CLiPs) play crucial roles in physiological
      and pathological processes, such as Alzheimer's disease and cancer. However, the
      mechanisms of substrate recognition by I-CLiPs remain poorly understood. The
      aspartic I-CLiP presenilin is the catalytic subunit of the gamma-secretase
      complex, which releases the amyloid-beta peptides (Abetas) through intramembrane
      proteolysis of the transmembrane domain of the amyloid precursor protein (APPTM).
      Here we used solution NMR to probe substrate docking of APPTM to the presenilin
      homologs (PSHs) MCMJR1 and MAMRE50, which cleaved APPTM in the NMR tube. Chemical
      shift perturbation (CSP) showed juxtamembrane regions of APPTM mediate its
      docking to MCMJR1. Binding of the substrate to I-CLiP decreased the magnitude of
      amide proton chemical shifts deltaH at the C-terminal half of the substrate
      APPTM, indicating that the docking to the enzyme weakens helical hydrogen bonds
      and unwinds the substrate transmembrane helix around the initial epsilon-cleavage
      site. The APPTM V44M substitution linked to familial AD caused more CSP and
      helical unwinding around the epsilon-cleavage site. MAMRE50, which cleaved APPTM
      at a higher rate, also caused more CSP and helical unwinding in APPTM than
      MCMJR1. Our data suggest that docking of the substrate transmembrane helix and
      helical unwinding is coupled in intramembrane proteolysis and FAD mutation
      modifies enzyme/substrate interaction, providing novel insights into the
      mechanisms of I-CLiPs and AD drug discovery.

PMID- 30120255
TI  - Preparation and characterization of Sn/La co-doped TiO2 nanomaterials and their
      phase transformation and photocatalytic activity.
AB  - The pure, tin (Sn)-doped, lanthanum (La)-doped and Sn/La co-doped titanium
      dioxide (TiO2) nanomaterials were synthesized using sol-gel method followed by
      calcination at the temperature of 360  degrees C, 450  degrees C and 600  degrees
      C, respectively. The structures of the nanomaterials were characterized by X-ray
      diffraction (XRD), Thermogravimetric (TG), Differential Thermal Analysis (DTA),
      Scanning Electron Microscopy (SEM), Energy Dispersive Spectrum (EDS),
      Transmission Electron Microscopy (TEM), X-ray Photoelectron Spectrum (XPS),
      Diffuse Reflectance Spectrum (DRS), Photoluminescence Spectrum (PL), Brunauer
      Emmett-Teller Measurements (BET), respectively. The photocatalytic property of
      the photocatalysts under UV light was evaluated through the degradation of
      Rhodamine B (RhB). The results show that the anatase-rutile phase transition is
      promoted by Sn-doping while La-doping retards the phase transition. However, La
      doping plays a major role in the process of phase transformation. The
      photocatalytic activity of pure TiO2 is affected by annealing temperature
      remarkably and the optimal annealing temperature is 450  degrees C. The
      photocatalytic activity of TiO2 is enhanced significantly by Sn and La doping at
      three different temperatures. Sn/La-TiO2 exhibits the highest degradation rates
      and the fastest reaction rates probably owing to the synergistic effect of Sn4+
      and La3+ ions in inhibiting the recombination of photogenerated electron-hole
      pairs. The formation of extra surface hydroxyl groups and additional surface area
      are also beneficial for the photocatalytic activity.

PMID- 30120256
TI  - Na/K-ATPase Y260 Phosphorylation-mediated Src Regulation in Control of Aerobic
      Glycolysis and Tumor Growth.
AB  - We report here the identification of alpha1 Na/K-ATPase as a major regulator of
      the proto-oncogene Src kinase and the role of this regulation in control of
      Warburg effect and tumor growth. Specifically, we discovered Y260 in alpha1 Na/K
      ATPase as a Src-specific phosphorylation and binding site and that Y260
      phosphorylation is required for Src-mediated signal transduction in response to a
      number of stimuli including EGF. As such, it enables a dynamic control of aerobic
      glycolysis. However, such regulation appears to be lost or attenuated in human
      cancers as the expression of Na/K-ATPase alpha1 was significantly decreased in
      prostate, breast and kidney cancers, and further reduced in corresponding
      metastatic lesions in patient samples. Consistently, knockdown of alpha1 Na/K
      ATPase led to a further increase in lactate production and the growth of tumor
      xenograft. These findings suggest that alpha1 Na/K-ATPase works as a tumor
      suppressor and that a loss of Na/K-ATPase-mediated Src regulation may lead to
      Warburg phenotype in cancer.

PMID- 30120257
TI  - Invasive meningococcal disease in Shanghai, China from 1950 to 2016: implications
      for serogroup B vaccine implementation.
AB  - Serogroup B invasive meningococcal disease (IMD) is increasing in China, but
      little is known about the causative meningococci. Here, IMD and carriage isolates
      in Shanghai characterised and the applicability of different vaccines assessed.
      Seven IMD epidemic periods have been observed in Shanghai since 1950, with 460
      isolates collected including 169 from IMD and 291 from carriage. Analyses were
      divided according to the period of meningococcal polysaccharide vaccine (MPV)
      introduction: (i) pre-MPV-A, 1965-1980; (ii) post-MPV-A, 1981-2008; and (iii)
      post-MPV-A + C, 2009-2016. Over this period, IMD incidence decreased from
      55.4/100,000 to 0.71 then to 0.02, corresponding to successive changes in
      meningococcal type from serogroup A ST-5 complex (MenA:cc5) to MenC:cc4821, and
      finally MenB:cc4821. MenB IMD became predominant (63.2%) in the post-MPV-A + C
      period, and 50% of cases were caused by cc4821, with the highest incidence in
      infants (0.45/100,000) and a case-fatality rate of 9.5%. IMD was positively
      correlated with population carriage rates. Using the Bexsero Antigen Sequence
      Type (BAST) system, fewer than 25% of MenB isolates in the post-MPV-A + C period
      contained exact or predicted cross reactive matches to the vaccines Bexsero,
      Trumenba, or an outer membrane vesicle (OMV)-based vaccine, NonaMen. A unique IMD
      epidemiology was seen in China, changing periodically from epidemic to
      hyperepidemic and low-level endemic disease. At the time of writing, MenB IMD
      dominated IMD in Shanghai, with isolates potentially beyond coverage with
      licenced OMV- and protein-based MenB vaccines.

PMID- 30120259
TI  - Restriction on the local realism violation in three-qubit states and its relation
      with tripartite entanglement.
AB  - Quantum entanglement and non-locality are two special aspects of quantum
      correlations. The relationship between multipartite entanglement and non-locality
      is at the root of the foundations of quantum mechanics but there is still no
      general quantitative theory. In order to address this issue we analyze the
      relationship between tripartite non-locality and tripartite entanglement measure,
      called the three-tangle. We describe the states which give the extremal quantum
      values of a Bell-type inequality for a given value of the tripartite
      entanglement. Moreover, we show that such extremal states can be reached if one
      introduced an appropriate order induced by the three-pi entanglement measure.
      Finally, we derive an analytical expression relating tripartite entanglement to
      the maximal violations of the Bell-type inequalities.

PMID- 30120258
TI  - Genetics, personality and wellbeing. A twin study of traits, facets and life
      satisfaction.
AB  - Human wellbeing is influenced by personality traits, in particular neuroticism
      and extraversion. Little is known about which facets that drive these
      associations, and the role of genes and environments. Our aim was to identify
      personality facets that are important for life satisfaction, and to estimate the
      contribution of genetic and environmental factors in the association between
      personality and life satisfaction. Norwegian twins (N = 1,516, age 50-65,
      response rate 71%) responded to a personality instrument (NEO-PI-R) and the
      Satisfaction With Life Scale (SWLS). Regression analyses and biometric modeling
      were used to examine influences from personality traits and facets, and to
      estimate genetic and environmental contributions. Neuroticism and extraversion
      explained 24%, and personality facets accounted for 32% of the variance in life
      satisfaction. Four facets were particularly important; anxiety and depression in
      the neuroticism domain, and activity and positive emotions within extraversion.
      Heritability of life satisfaction was 0.31 (0.22-0.40), of which 65% was
      explained by personality-related genetic influences. The remaining genetic
      variance was unique to life satisfaction. The association between personality and
      life satisfaction is driven mainly by four, predominantly emotional, personality
      facets. Genetic factors play an important role in these associations, but
      influence life satisfaction also beyond the effects of personality.

PMID- 30120260
TI  - Patterns of early primary school-based literacy interventions among Pacific
      children from a nationwide health screening programme of 4 year olds.
AB  - Literacy success is critical to unlocking a child's potential and enhancing their
      future wellbeing. Thus, the early identification and redressing of literacy needs
      is vital. Pacific children have, on average, the lowest literacy achievement
      levels in New Zealand. However, this population is very diverse. This study
      sought to determine whether the current national health screening programme of
      pre-school children could be used as an early detection tool of Pacific children
      with the greatest literacy needs. Time-to-event analyses of literacy intervention
      data for Pacific children born in years 2005-2011 were employed. A multivariable
      Cox proportional hazard model was fitted, and predictive assessment made using
      training and test datasets. Overall, 59,760 Pacific children were included, with
      6,861 (11.5%) receiving at least one literacy intervention. Tongan (hazard ratio
      [HR]: 1.33; 95% confidence interval [CI]: 1.23, 1.45) and Cook Island Maori (HR:
      1.33; 95% CI: 1.21, 1.47) children were more likely to receive an intervention
      than Samoan children; whereas those children with both Pacific and non-Pacific
      ethnic identifications were less likely. However, the multivariable model lacked
      reasonable predictive power (Harrell's c-statistic: 0.592; 95% CI: 0.583, 0.602).
      Regardless, important Pacific sub-populations emerged who would benefit from
      targeted literacy intervention or policy implementation.

PMID- 30120261
TI  - A centuries-long delay between a paleo-ice-shelf collapse and grounding-line
      retreat in the Whales Deep Basin, eastern Ross Sea, Antarctica.
AB  - Recent thinning and loss of Antarctic ice shelves has been followed by near
      synchronous acceleration of ice flow that may eventually lead to sustained
      deflation and significant contraction in the extent of grounded and floating ice.
      Here, we present radiocarbon dates from foraminifera that constrain the time
      elapsed between a previously described paleo-ice-shelf collapse and the
      subsequent major grounding-line retreat in the Whales Deep Basin (WDB) of eastern
      Ross Sea. The dates indicate that West Antarctic Ice Sheet (WAIS) grounding-line
      retreat from the continental shelf edge was underway prior to 14.7 +/- 0.4 cal
      kyr BP. A paleo-ice-shelf collapse occurred at 12.3 +/- 0.2 cal kyr BP. The
      grounding position was maintained on the outer-continental shelf until at least
      11.5 +/- 0.3 cal kyr BP before experiencing a 200-km retreat. Given the age
      uncertainties, the major grounding-line retreat lagged ice-shelf collapse by at
      least two centuries and by as much as fourteen centuries. In the WDB, the
      centuries-long delay in the retreat of grounded ice was partly due to rapid
      aggradational stacking of an unusually large volume of grounding-zone-wedge
      sediment as ice-stream discharge accelerated following ice-shelf collapse. This
      new deglacial reconstruction shows that ongoing changes to ice shelves may
      trigger complex dynamics whose consequences are realized only after a significant
      lag.

PMID- 30120262
TI  - Time-reversal invariant resonant backscattering on a topological insulator
      surface driven by a time-periodic gate voltage.
AB  - We study the scattering of the Dirac electrons by a point-like nonmagnetic
      impurity on the surface of a topological insulator, driven by a time-periodic
      gate voltage. It is found that, due to the doublet degenerate crossing points of
      different Floquet sidebands, resonant backscattering can happen for the surface
      electrons, even without breaking the time-reversal (TR) symmetry of the
      topological surface states (TSSs). The energy spectrum is reshuffled in a way
      quite different from that for the circularly polarized light, so that new
      features are exhibited in the Friedel oscillations of the local charge and spin
      density of states. Although the electron scattering is dramatically modified by
      the driving voltage, the 1/rho scale law of the spin precession persists for the
      TSSs. The TR invariant backscattering provides a possible way to engineer the
      Dirac electronic spectrum of the TSSs, without destroying the unique property of
      spin-momentum interlocking of the TSSs.

PMID- 30120263
TI  - Transcriptional insights into the pyramided resistance to rice bacterial blight.
AB  - The pyramiding of resistance (R) genes provides broad-spectrum and durable
      resistance to plant diseases. However, the genetic basis for bacterial blight
      (BB) resistance remains unclear. The BB R gene pyramided line IRBB54, which
      expresses xa5 and Xa21, possessed a higher level of resistance than both single R
      gene lines. Large-scale genotyping of genetic markers in this study revealed
      similar genetic backgrounds among the near-isogenic lines (NILs), suggesting that
      resistance in the resistant NILs was mainly conferred by the individual R genes
      or the interaction between them. Transcriptome analysis demonstrated that more
      than 50% of the differentially expressed genes (DEGs), and more than 70% of the
      differentially expressed functions, were shared between IRBB54 and IRBB5 or
      IRBB21. Most of the DEGs in the resistant NILs were downregulated and are
      predicted to function in cellular and biological process. The DEGs common among
      the resistant NILs mainly showed non-additive expression patterns and enrichment
      in stress-related pathways. The differential expression of agronomic trait
      controlled genes in the resistant NILs, especially in IRBB54, indicated the
      existence of potential side-effects resulting from gene pyramiding. Our findings
      contribute to the understanding of R gene pyramiding, as well as its effects on
      targeted and non-targeted trait(s).

PMID- 30120264
TI  - Effect of China's maternal health policy on improving rural hospital delivery:
      Evidence from two cross-sectional surveys.
AB  - This population-based cross-sectional study aims to explore the effect of China's
      Rural Hospital Delivery Subsidy (RHDS) policy on the utilization of women's
      hospital delivery between rural and urban areas. A total of 2398 women were drawn
      from the Fourth and Fifth National Health Service Surveys, from the Shaanxi
      province. A generalized linear mixed model was used to analyze the influence of
      the RHDS policy on the hospital delivery rate. Concentration index and
      decomposition methods were used to explore the equity of hospital delivery
      utilization. Prior to introduction of the RHDS policy, the difference in hospital
      delivery rates was -0.09 (95% CL: -0.16, -0.01) between rural and urban women
      when adjusting the influence of socioeconomic factors on hospital delivery; after
      implementation of the policy, the difference was reduced to 0.02 (95% CL: -0.01,
      0.06). The horizontal inequity index was reduced from 0.084 to 0.009 for rural
      women and from 0.070 to 0.011 for urban women. China's Rural Hospital Delivery
      Subsidy policy had some positive effect on reducing the gap between rural and
      urban women's hospital delivery rate and inequity. However, there is still a pro
      rich inequity of hospital delivery utilization for both rural and urban women.

PMID- 30120265
TI  - Development and Validation of the Computerised Adaptive Beat Alignment Test (CA
      BAT).
AB  - Beat perception is increasingly being recognised as a fundamental musical
      ability. A number of psychometric instruments have been developed to assess this
      ability, but these tests do not take advantage of modern psychometric techniques,
      and rarely receive systematic validation. The present research addresses this gap
      in the literature by developing and validating a new test, the Computerised
      Adaptive Beat Alignment Test (CA-BAT), a variant of the Beat Alignment Test (BAT)
      that leverages recent advances in psychometric theory, including item response
      theory, adaptive testing, and automatic item generation. The test is constructed
      and validated in four empirical studies. The results support the reliability and
      validity of the CA-BAT for laboratory testing, but suggest that the test is not
      well-suited to online testing, owing to its reliance on fine perceptual
      discrimination.

PMID- 30120267
TI  - Assessing the Use of Influenza Forecasts and Epidemiological Modeling in Public
      Health Decision Making in the United States.
AB  - Although forecasts and other mathematical models have the potential to play an
      important role in mitigating the impact of infectious disease outbreaks, the
      extent to which these tools are used in public health decision making in the
      United States is unclear. Throughout 2015, we invited public health practitioners
      belonging to three national public health organizations to complete a cross
      sectional survey containing questions on model awareness, model use, and
      communication with modelers. Of 39 respondents, 46.15% used models in their work,
      and 20.51% reported direct communication with those who create models. Over half
      (64.10%) were aware that influenza forecasts exist. The need for improved
      communication between practitioners and modelers was overwhelmingly endorsed,
      with over 50% of participants indicating the need for models more relevant to
      public health questions, increased frequency of telecommunication, and more plain
      language in discussing models. Model use for public health decision making must
      be improved if models are to reach their full potential as public health tools.
      Increased quality and frequency of communication between practitioners and
      modelers could be particularly useful in achieving this goal. It is important
      that improvements be made now, rather than waiting for the next public health
      crisis to occur.

PMID- 30120266
TI  - Tdp-25 Routing to Autophagy and Proteasome Ameliorates its Aggregation in
      Amyotrophic Lateral Sclerosis Target Cells.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that
      primarily affects motoneurons, while non-neuronal cells may contribute to disease
      onset and progression. Most ALS cases are characterized by the mislocalization
      and aggregation of the TAR DNA binding protein 43 (TDP-43) in affected cells. TDP
      43 aggregates contain C-terminal TDP-43 fragments of 35 kDa (TDP-35) and 25 kDa
      (TDP-25) and have been mainly studied in motoneurons, while little is currently
      known about their rate of accumulation and clearance in myoblasts. Here, we
      performed a comparative study in immortalized motoneuronal like (NSC34; i
      motoneurons) cells and stabilized myoblasts (C2C12; s-myoblasts) to evaluate if
      these two cell types differentially accumulate and clear TDP forms. The most
      aggregating specie in i-motoneurons is the TDP-25 fragment, mainly constituted by
      the "prion-like" domain of TDP-43. To a lower extent, TDP-25 also aggregates in s
      myoblasts. In both cell types, all TDP species are cleared by proteasome, but TDP
      25 impairs autophagy. Interestingly, the routing of TDP-25 fragment to
      proteasome, by overexpressing BAG1, or to autophagy, by overexpressing HSPB8 or
      BAG3 decreased its accumulation in both cell types. These results demonstrate
      that promoting the chaperone-assisted clearance of ALS-linked proteins is
      beneficial not only in motoneurons but also in myoblasts.

PMID- 30120268
TI  - Indibulin dampens microtubule dynamics and produces synergistic antiproliferative
      effect with vinblastine in MCF-7 cells: Implications in cancer chemotherapy.
AB  - Indibulin, a synthetic inhibitor of tubulin assembly, has shown promising
      anticancer activity with a minimal neurotoxicity in preclinical animal studies
      and in Phase I clinical trials for cancer chemotherapy. Using time-lapse confocal
      microscopy, we show that indibulin dampens the dynamic instability of individual
      microtubules in live breast cancer cells. Indibulin treatment also perturbed the
      localization of end-binding proteins at the growing microtubule ends in MCF-7
      cells. Indibulin reduced inter-kinetochoric tension, produced aberrant spindles,
      activated mitotic checkpoint proteins Mad2 and BubR1, and induced mitotic arrest
      in MCF-7 cells. Indibulin-treated MCF-7 cells underwent apoptosis-mediated cell
      death. Further, the combination of indibulin with an anticancer drug vinblastine
      was found to exert synergistic cytotoxic effects on MCF-7 cells. Interestingly,
      indibulin displayed a stronger effect on the undifferentiated neuroblastoma (SH
      SY5Y) cells than the differentiated neuronal cells. Unlike indibulin, vinblastine
      and colchicine produced similar depolymerizing effects on microtubules in both
      differentiated and undifferentiated SH-SY5Y cells. The data indicated a
      possibility that indibulin may reduce chemotherapy-induced peripheral neuropathy
      in cancer patients.

PMID- 30120269
TI  - AIEC infection triggers modification of gut microbiota composition in genetically
      predisposed mice, contributing to intestinal inflammation.
AB  - A high prevalence of adherent-invasive E. coli (AIEC) in the intestinal mucosa of
      Crohn's disease patients has been shown. AIEC colonize the intestine and induce
      inflammation in genetically predisposed mouse models including CEABAC10
      transgenic (Tg) mice expressing human CEACAM6-receptor for AIEC and eif2ak4-/-
      mice exhibiting autophagy defect in response to AIEC infection. Here, we aimed at
      investigating whether gut microbiota modification contributes to AIEC-induced
      intestinal inflammation in these mouse models. For this, eif2ak4+/+ and eif2ak4-/
      mice or CEABAC10 Tg mice invalidated for Eif2ak4 gene (Tg/eif2ak4-/-) or not
      (Tg/eif2ak4+/+) were infected with the AIEC reference strain LF82 or the non
      pathogenic E. coli K12 MG1655 strain. In all mouse groups, LF82 colonized the gut
      better and longer than MG1655. No difference in fecal microbiota composition was
      observed in eif2ak4+/+ and eif2ak4-/- mice before infection and at day 1 and 4
      post-infection. LF82-infected eif2ak4-/- mice exhibited altered fecal microbiota
      composition at day 14 and 21 post-infection and increased fecal lipocalin-2 level
      at day 21 post-infection compared to other groups, indicating that intestinal
      inflammation developed after microbiota modification. Similar results were
      obtained for LF82-infected Tg/eif2ak4-/- mice. These results suggest that in
      genetically predisposed hosts, AIEC colonization might induce chronic intestinal
      inflammation by altering the gut microbiota composition.

PMID- 30120272
TI  - Publisher Correction: Across-subject offline decoding of motor imagery from MEG
      and EEG.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30120270
TI  - Membrane-Modulating Drugs can Affect the Size of Amyloid-beta25-35 Aggregates in
      Anionic Membranes.
AB  - The formation of amyloid-beta plaques is one of the hallmarks of Alzheimer's
      disease. The presence of an amphiphatic cell membrane can accelerate the
      formation of amyloid-beta aggregates, making it a potential druggable target to
      delay the progression of Alzheimer's disease. We have prepared unsaturated
      anionic membranes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)
      and 1,2-dimyristoyl-sn-glycero-3-phospho-L-serine (DMPS) and added the trans
      membrane segment Abeta25-35. Peptide plaques spontaneously form in these
      membranes at high peptide concentrations of 20 mol%, which show the
      characteristic cross-beta motif (concentrations are relative to the number of
      membrane lipids and indicate the peptide-to-lipid ratio). We used atomic force
      microscopy, fluorescence microscopy, x-ray microscopy, x-ray diffraction, UV-vis
      spectroscopy and Molecular Dynamics (MD) simulations to study three membrane
      active molecules which have been speculated to have an effect in Alzheimer's
      disease: melatonin, acetylsalicyclic acid (ASA) and curcumin at concentrations of
      5 mol% (drug-to-peptide ratio). Melatonin did not change the structural
      parameters of the membranes and did not impact the size or extent of peptide
      clusters. While ASA led to a membrane thickening and stiffening, curcumin made
      membranes softer and thinner. As a result, ASA was found to lead to the formation
      of larger peptide aggregates, whereas curcumin reduced the volume fraction of
      cross-beta sheets by ~70%. We speculate that the interface between membrane and
      peptide cluster becomes less favorable in thick and stiff membranes, which favors
      the formation of larger aggregates, while the corresponding energy mismatch is
      reduced in soft and thin membranes. Our results present evidence that cross-beta
      sheets of Abeta25-35 in anionic unsaturated lipid membranes can be re-dissolved
      by changing membrane properties to reduce domain mismatch.

PMID- 30120271
TI  - An Evaluation of the Collagen Fragments Related to Fibrogenesis and Fibrolysis in
      Nonalcoholic Steatohepatitis.
AB  - Fibrosis, resulted from the imbalance of fibrogenesis and fibrolysis, is a key
      readout of disease progression in nonalcoholic steatohepatitis (NASH) and
      reflects mortality risk. Non-invasive biomarkers capable of diagnosing fibrosis
      stages and monitoring fibrosis changes in NASH patients are urgently needed. This
      study is to evaluate collagen formation and degradation biomarkers, reflective of
      fibrogenesis or fibrolysis, in patients with biopsy proven NASH. Collagen
      formation biomarker PRO-C3 and PRO-C6 levels were significantly higher in
      patients with advanced fibrosis stage 3-4 than those with fibrosis stage 0-2.
      Elevated PRO-C3 levels were also associated with severe lobular inflammation and
      ballooning, but not with steatosis. Multivariate logistic regression analysis
      identified PRO-C3 and PRO-C6 to be independently related to fibrosis stage. PRO
      C3 showed similar performance to identify patients with advanced fibrosis in
      discovery and validation cohorts. Furthermore, in a longitudinal study cohort
      with paired biopsies, mean PRO-C3 increased with worsening of fibrosis and
      decreased with fibrosis improvement. The results suggest that PRO-C3 may be a
      potentially useful biomarker in identifying patients with advanced fibrosis and
      active fibrogenesis, as well as in assessing changes in fibrosis over time. It is
      worthy of further evaluation to confirm its diagnostic value and clinical
      utility.

PMID- 30120273
TI  - Porous SnO2 nanoparticles based ion chromatographic determination of non
      fluorescent antibiotic (chloramphenicol) in complex samples.
AB  - Nowadays, there are rising concerns about the extensive use of the antibiotics
      such as chloramphenicol (CAP), has threatened the human life in the form of
      various vicious diseases. The limited selectivity and sensitivity of confirmatory
      techniques (UV and electrochemical) and non-fluorescence property of CAP make its
      determination a challenging task in the modern pharmaceutical analysis. In order
      to redeem the selective, sensitive and cost-effective fluorescence methodology,
      here by the dual role of synthesized porous SnO2 nanoparticles were exploited;
      (i) a porous sorbent in a u-QuEChERS based sample preparation and as (ii) a
      stimulant for the transformation of non-fluorescent analytes namely CAP and p
      nitrophenol (p-NP) into their respective fluorescent product. We report a green,
      simple, selective and cost effective ion chromatographic method for CAP sensitive
      determination in three complex matrices including milk, human urine and serum.
      The synthesized sorbent not only selectively adsorbed and degraded the
      matrix/interferences but also selectively reduced the non-fluorescent antibiotic
      CAP into a fluorescent species. This developed ion chromatographic method
      exhibited good selectivity, linearity (r2 >= 0.996) and limit of detection (LOD)
      was in the range 0.0201-0.0280 ug/kg. The inter- and intraday precisions were
      also satisfactory having a relative standard deviation (RSDs) less than 14.96%
      and excellent recoveries of CAP in the range of 78.3-100.2% were retrieved in
      various complex samples.

PMID- 30120275
TI  - Subwavelength Interferometric Control of Absorption in Three-port Acoustic
      Network.
AB  - Utilizing the effect of losses, we show that symmetric 3-port devices exhibit
      coherent perfect absorption of waves and we provide the corresponding conditions
      on the reflection and transmission coefficients. Infinite combinations of
      asymmetric inputs with different amplitudes and phase at each port as well as a
      completely symmetric input, are found to be perfectly absorbed. To illustrate the
      above we study an acoustic 3-port network operating in a subwavelength frequency
      both theoretically and experimentally. In addition we show how the output from a
      3-port network is altered, when conditions of perfect absorption are met but the
      input waves phase and amplitude vary. In that regard, we propose optimized
      structures which feature both perfect absorption and perfect transmission at the
      same frequency by tuning the amplitudes and phases of the input waves.

PMID- 30120276
TI  - Large networks of rational agents form persistent echo chambers.
AB  - Echo chambers (ECs) are enclosed epistemic circles where like-minded people
      communicate and reinforce pre-existing beliefs. It remains unclear if cognitive
      errors are necessarily required for ECs to emerge, and then how ECs are able to
      persist in networks with available contrary information. We show that ECs can
      theoretically emerge amongst error-free Bayesian agents, and that larger networks
      encourage rather than ameliorate EC growth. This suggests that the network
      structure itself contributes to echo chamber formation. While cognitive and
      social biases might exacerbate EC emergence, they are not necessary conditions.
      In line with this, we test stylized interventions to reduce EC formation, finding
      that system-wide truthful 'educational' broadcasts ameliorate the effect, but do
      not remove it entirely. Such interventions are shown to be more effective on
      agents newer to the network. Critically, this work serves as a formal argument
      for the responsibility of system architects in mitigating EC formation and
      retention.

PMID- 30120274
TI  - Complete chloroplast genome sequence of Fagopyrum dibotrys: genome features,
      comparative analysis and phylogenetic relationships.
AB  - Fagopyrum dibotrys, belongs to Polygonaceae family, is one of national key
      conserved wild plants of China with important medicinal and economic values.
      Here, the complete chloroplast (cp) genome sequence of F. dibotrys is reported.
      The cp genome size is 159,919 bp with a typical quadripartite structure and
      consisting of a pair of inverted repeat regions (30,738 bp) separated by large
      single copy region (85,134 bp) and small single copy region (13,309 bp).
      Sequencing analyses indicated that the cp genome encodes 131 genes, including 80
      protein-coding genes, 28 tRNA genes and 4 rRNA genes. The genome structure, gene
      order and codon usage are typical of angiosperm cp genomes. We also identified 48
      simple sequence repeats (SSR) loci, fewer of them are distributed in the protein
      coding sequences compared to the noncoding regions. Comparison of F. dibotrys cp
      genome to other Polygonaceae cp genomes indicated the inverted repeats (IRs) and
      coding regions were more conserved than single copy and noncoding regions, and
      several variation hotspots were detected. Coding gene sequence divergence
      analyses indicated that five genes (ndhK, petL rpoC2, ycf1, ycf2) were subject to
      positive selection. Phylogenetic analysis among 42 species based on cp genomes
      and 50 protein-coding genes indicated a close relationship between F. dibotrys
      and F. tataricum. In summary, the complete cp genome sequence of F. dibotrys
      reported in this study will provide useful plastid genomic resources for
      population genetics and pave the way for resolving phylogenetic relationships of
      order Caryophyllales.

PMID- 30120277
TI  - Effects of multiple environmental variables on tundra ecosystem respiration in
      maritime Antarctica.
AB  - Summertime ecosystem respiration (ER) rates through seven sites were measured at
      an upland tundra on Fildes Peninsula in maritime Antarctica to investigate
      effects of topographic gradient, vegetation types and climatic factors on tundra
      ER rates. Overall the highest ER rates occurred at the tundra top, followed at
      the middle slope, and the lowest rates at the lower slope. The daily highest ER
      rates occurred at noon whereas the lowest at 6 am. There was a significant
      positive correlation (P < 0.05) between tundra ER and 0-10 cm soil temperature,
      but a significant negative correlation (P < 0.01) between ER and soil moisture. A
      high Q10 value of 2.69 was obtained when all the data were combined, indicating
      soil temperature sensitivity of tundra ER. The mean ER at the tundra sites with
      moss coverage (72.2 +/- 4.4 mg CO2 m-2 h-1) was significantly higher (P < 0.01)
      than that at the sites with lichen coverage (46.8 +/- 8.7 mg CO2 m-2 h-1). The
      tundra sites without snow coverage experienced significant CO2 release, whereas
      the emission through ER was very low at the tundra sites with snow coverage. Our
      results indicated that topographic gradient, soil temperature, soil moisture,
      vegetation types and snow coverage might affect tundra ER in maritime Antarctica.

PMID- 30120278
TI  - Mapping temporal-network percolation to weighted, static event graphs.
AB  - The dynamics of diffusion-like processes on temporal networks are influenced by
      correlations in the times of contacts. This influence is particularly strong for
      processes where the spreading agent has a limited lifetime at nodes: disease
      spreading (recovery time), diffusion of rumors (lifetime of information), and
      passenger routing (maximum acceptable time between transfers). We introduce
      weighted event graphs as a powerful and fast framework for studying connectivity
      determined by time-respecting paths where the allowed waiting times between
      contacts have an upper limit. We study percolation on the weighted event graphs
      and in the underlying temporal networks, with simulated and real-world networks.
      We show that this type of temporal-network percolation is analogous to directed
      percolation, and that it can be characterized by multiple order parameters.

PMID- 30120280
TI  - A 200-year annually laminated stalagmite record of precipitation seasonality in
      southeastern China and its linkages to ENSO and PDO.
AB  - In southeastern China (SEC), the precipitation amount produced by the East Asian
      summer monsoon (EASM) is almost equivalent to that during the non-summer monsoon
      (NSM) period, both of them significantly affecting agriculture and socioeconomy.
      Here, we present a seasonally-resolved stalagmite delta18O record (delta18Os) for
      the interval 1810-2009 AD from E'mei cave, Jiangxi Province, SEC. The comparison
      between delta18Os and instrumental data indicates that the delta18Os variability
      is primarily controlled by the precipitation seasonality (i.e., the ratio of
      EASM/NSM precipitation) modulated by the El Nino/Southern Oscillation (ENSO) on
      interannual to interdecadal timescales. Higher (lower) delta18Os values thereby
      correspond to lower (higher) EASM/NSM ratios associated with El Nino (La Nina)
      events. Significant correlations with ENSO and the Pacific Decadal Oscillation
      (PDO) indicate that the precipitation seasonality in SEC is remarkably influenced
      by ocean-atmosphere interactions, with lower (higher) EASM/NSM ratios during warm
      (cold) phases of ENSO/PDO. The progressive increase in delta18Os since 2005 AD
      may reflect a strengthening of the central Pacific El Nino under continued
      anthropogenic global warming. The relationship between seasonal precipitation and
      delta18Os with ENSO/PDO requires further studies.

PMID- 30120279
TI  - Synthesis of biogenic silver nanoparticles using Althaea officinalis as reducing
      agent: evaluation of toxicity and ecotoxicity.
AB  - Silver nanoparticles (AgNPs) are known mainly because of their bactericidal
      properties. Among the different types of synthesis, there is the biogenic
      synthesis, which allows the synergy between the nanocomposites and substances
      from the organism employed for the synthesis. This study describes the synthesis
      of AgNPs using infusion of roots (AgNpR) and extract (AgNpE) of the plant Althaea
      officinalis. After the synthesis through reduction of silver nitrate with
      compounds of A. officinalis, physico-chemical analyzes were performed by UV-Vis
      spectroscopy, nanoparticles tracking analysis (NTA), dynamic light scattering
      (DLS) and scanning electron microscopy (SEM). Toxicity was evaluated through
      Allium cepa assay, comet test with cell lines, cell viability by mitochondrial
      activity and image cytometry and minimal inhibitory concentration on pathogenic
      microorganisms. Biochemical analyzes (CAT - catalase, GPx - glutathione
      peroxidase e GST - glutationa S-transferase) and genotoxicity evaluation in vivo
      on Zebrafish were also performed. AgNpE and AgNpR showed size of 157 +/- 11 nm
      and 293 +/- 12 nm, polydispersity of 0.47 +/- 0.08 and 0.25 +/- 0.01, and zeta
      potential of 20.4 +/- 1.4 and 26.5 +/- 1.2 mV, respectively. With regard to
      toxicity, the AgNpE were the most toxic when compared with AgNpR. Biochemical
      analyzes on fish showed increase of CAT activity in most of the organs, whereas
      GPx showed few changes and the activity of GST decreased. Also regarding to
      bactericidal activity, both nanoparticles were effective, however AgNpR showed
      greater activity. Althaea officinalis can be employed as reducing agent for the
      synthesis of silver nanoparticles, although it is necessary to consider its
      potential toxicity and ecotoxicity.

PMID- 30120281
TI  - Quantitative prediction of long-term molecular response in TKI-treated CML -
      Lessons from an imatinib versus dasatinib comparison.
AB  - Longitudinal monitoring of BCR-ABL transcript levels in peripheral blood of CML
      patients treated with tyrosine kinase inhibitors (TKI) revealed a typical
      biphasic response. Although second generation TKIs like dasatinib proved more
      efficient in achieving molecular remission compared to first generation TKI
      imatinib, it is unclear how individual responses differ between the drugs and
      whether mechanisms of drug action can be deduced from the dynamic data. We use
      time courses from the DASISION trial to address statistical differences in the
      dynamic response between first line imatinib vs. dasatinib treatment cohorts and
      we analyze differences between the cohorts by fitting an established mathematical
      model of functional CML treatment to individual time courses. On average,
      dasatinib-treated patients show a steeper initial response, while the long-term
      response only marginally differed between the treatments. Supplementing each
      patient time course with a corresponding confidence region, we illustrate the
      consequences of the uncertainty estimate for the underlying mechanisms of CML
      remission. Our model suggests that the observed BCR-ABL dynamics may result from
      different, underlying stem cell dynamics. These results illustrate that the
      perception and description of CML treatment response as a dynamic process on the
      level of individual patients is a prerequisite for reliable patient-specific
      response predictions and treatment optimizations.

PMID- 30120282
TI  - 3D Bioprinted Human Skeletal Muscle Constructs for Muscle Function Restoration.
AB  - A bioengineered skeletal muscle tissue as an alternative for autologous tissue
      flaps, which mimics the structural and functional characteristics of the native
      tissue, is needed for reconstructive surgery. Rapid progress in the cell-based
      tissue engineering principle has enabled in vitro creation of cellularized muscle
      like constructs; however, the current fabrication methods are still limited to
      build a three-dimensional (3D) muscle construct with a highly viable, organized
      cellular structure with the potential for a future human trial. Here, we applied
      3D bioprinting strategy to fabricate an implantable, bioengineered skeletal
      muscle tissue composed of human primary muscle progenitor cells (hMPCs). The
      bioprinted skeletal muscle tissue showed a highly organized multi-layered muscle
      bundle made by viable, densely packed, and aligned myofiber-like structures. Our
      in vivo study presented that the bioprinted muscle constructs reached 82% of
      functional recovery in a rodent model of tibialis anterior (TA) muscle defect at
      8 weeks of post-implantation. In addition, histological and immunohistological
      examinations indicated that the bioprinted muscle constructs were well integrated
      with host vascular and neural networks. We demonstrated the potential of the use
      of the 3D bioprinted skeletal muscle with a spatially organized structure that
      can reconstruct the extensive muscle defects.

PMID- 30120283
TI  - Acute Physical Activity Enhances Executive Functions in Children with ADHD.
AB  - Acute physical activity of moderate to vigorous intensity has been shown to
      improve cognitive functions in children. However, the empirical evidence
      associated with Attention Deficit Hyperactivity Disorder (ADHD) in children is
      still limited, in particular regarding which specific cognitive functions
      benefit. This study investigated the effects of an acute bout of physical
      activity on multiple aspects of executive functions (inhibition, switching, and
      visual working memory) in children with ADHD. Forty-six children (8-12 years old;
      82.6% boys) were randomly assigned to either 15 minutes of acute exergaming
      (physical activity of moderate intensity) or to a control condition (sedentary).
      Executive function performance in inhibition, switching and visual working memory
      were assessed before and after each condition, using a modified version of both
      the Flanker and the Color Span Backwards Task. The results revealed that
      participants in the exergaming group performed significantly faster than those in
      the control group in terms of both inhibition and switching, but there was no
      significant difference in the accuracy of the two tasks nor in visual working
      memory performance. These findings suggest that acute physical activity utilizing
      exergaming has the potential to improve specific aspects of executive functions
      (reaction times in inhibition and switching) in children with ADHD.

PMID- 30120284
TI  - Prediction of Ewing Sarcoma treatment outcome using attenuated tissue reflection
      FTIR tissue spectroscopy.
AB  - Ewing sarcoma is the second most common type of primary bone cancer and
      predominantly affects children and young people. Improved outcome prediction is
      key to delivering risk-adjusted, appropriate and effective care to cancer
      patients. Advances in the Fourier Transform Infrared (FTIR) spectroscopy of
      tissues enable it to be a non-invasive method to obtain information about the
      biochemical content of any biological sample. In this retrospective study,
      attenuated tissue reflection FTIR spectroscopy of biopsy samples from paediatric
      patients reveals spectral features that are diagnostic for Ewing Sarcoma.
      Furthermore, our results suggest that spectral features such as these may be of
      value for the prediction of treatment outcome independent to well-known,
      routinely used risk factors.

PMID- 30120286
TI  - Investigation of optical force on magnetic nanoparticles with magnetic-fluid
      filled Fabry-Perot interferometer.
AB  - The optical force acting on the magnetic nanoparticles (MNPs) is investigated
      with the magnetic-fluid-filled fiber-optic Fabry-Perot interferometer. The shift
      of interference spectra is related with the local refractive index variation in
      the light path, which is assigned to the optical-force-induced outward movement
      of MNPs. The influence of magnetic fluid's viscosity, ambient temperature,
      strength and orientation of the externally applied magnetic field on the optical
      force-induced MNPs' movement is studied in details. The results of this work
      provide a further understanding of interaction between light and MNPs and clarify
      the dynamic micro-processes of MNPs within magnetic fluid under external stimuli.
      It may have the potentials in the fields of light-controllable magnetic-fluid
      based devices and vector magnetic field detection.

PMID- 30120285
TI  - Complementary iTRAQ-based proteomic and RNA sequencing-based transcriptomic
      analyses reveal a complex network regulating pomegranate (Punica granatum L.)
      fruit peel colour.
AB  - Peel colour is an important factor affecting the marketability of pomegranate
      fruits. Therefore, elucidating the genetic mechanism of fruit peel colour
      development may be useful for breeding pomegranate cultivars with enhanced fruit
      peel colours. In this study, we combined an iTRAQ-based proteome-level analysis
      with an RNA sequencing-based transcriptome-level analysis to detect the proteins
      and genes related to fruit peel colour development in pomegranate. We analysed
      the 'Tunisia' (red fruit) and 'White' (white fruit) pomegranate cultivars at two
      stages of fruit development. A total of 27 differentially abundant proteins
      (increased abundance) and 54 differentially expressed genes (16 up-regulated and
      38 down-regulated) were identified from our proteomics and transcriptomics data.
      The identified proteins and genes contribute to pomegranate fruit peel colour by
      participating in the biosynthesis of anthocyanins, stilbenoids, diarylheptanoids,
      gingerols, flavonoids, and phenylpropanoids. Several candidate proteins and genes
      corresponded to enzymes related to general reactions (PAL, 4CL, DFR, LDOX/ANS,
      CHS, and F3'5'H) and glycosylation (GT1 and UGAT) of compounds and pigments
      related to the colour of pomegranate fruit peel. Complementary proteome- and
      transcriptome-level analyses revealed a complex molecular network controlling
      fruit peel colour. The candidate genes identified in this study may be useful for
      the marker-based breeding of new pomegranate cultivars.

PMID- 30120287
TI  - Locus Coeruleus atrophy doesn't relate to fatigue in Parkinson's disease.
AB  - Fatigue is a frequent complaint among healthy population and one of the earliest
      and most debilitating symptoms in Parkinson's disease (PD). Earlier studies have
      examined the role of dopamine and serotonin in pathogenesis of fatigue, but the
      plausible role of noradrenalin (NA) remains underexplored. We investigated the
      relationship between fatigue in Parkinsonian patients and the extent of
      degeneration of Locus Coeruleus (LC), the main source of NA in the brain. We
      quantified LC and Substantia Nigra (SN) atrophy using neuromelanin-sensitive
      imaging, analyzed with a novel, fully automated algorithm. We also assessed
      patients' fatigue, depression, sleep disturbance and vigilance. We found that LC
      degeneration correlated with the levels of depression and vigilance but not with
      fatigue, while fatigue correlated weakly with atrophy of SN. These results
      indicate that LC degeneration in Parkinson's disease is unlikely to cause
      fatigue, but may be involved in mood and vigilance alterations.

PMID- 30120288
TI  - Predictive ability of genome-assisted statistical models under various forms of
      gene action.
AB  - Recent work has suggested that the performance of prediction models for complex
      traits may depend on the architecture of the target traits. Here we compared
      several prediction models with respect to their ability of predicting phenotypes
      under various statistical architectures of gene action: (1) purely additive, (2)
      additive and dominance, (3) additive, dominance, and two-locus epistasis, and (4)
      purely epistatic settings. Simulation and a real chicken dataset were used.
      Fourteen prediction models were compared: BayesA, BayesB, BayesC, Bayesian LASSO,
      Bayesian ridge regression, elastic net, genomic best linear unbiased prediction,
      a Gaussian process, LASSO, random forests, reproducing kernel Hilbert spaces
      regression, ridge regression (best linear unbiased prediction), relevance vector
      machines, and support vector machines. When the trait was under additive gene
      action, the parametric prediction models outperformed non-parametric ones.
      Conversely, when the trait was under epistatic gene action, the non-parametric
      prediction models provided more accurate predictions. Thus, prediction models
      must be selected according to the most probably underlying architecture of
      traits. In the chicken dataset examined, most models had similar prediction
      performance. Our results corroborate the view that there is no universally best
      prediction models, and that the development of robust prediction models is an
      important research objective.

PMID- 30120289
TI  - A novel ZIC3 gene mutation identified in patients with heterotaxy and congenital
      heart disease.
AB  - Heterotaxy syndrome (HTX) is characterized by left-right (LR) asymmetry
      disturbances associated with severe heart malformations. However, the exact
      genetic cause of HTX pathogenesis remains unclear. The aim of this study was to
      investigate the pathogenic mechanism underlying heterotaxy syndrome. Targeted
      next-generation sequencing (NGS) was performed for twenty-two candidate genes
      correlated with LR axis development in sixty-six HTX patients from unrelated
      families. Variants were filtered from databases and predicted in silico using
      prediction programs. A total of twenty-one potential disease-causing variants
      were identified in seven genes. Next, we used Sanger sequencing to confirm the
      identified variants in the family pedigree and found a novel hemizygous mutation
      (c.890G > T, p.C297F) in the ZIC3 gene in a male patient that was inherited from
      his mother, who was a carrier. The results of functional indicated that this ZIC3
      mutation decreases transcriptional activity, affects the affinity of the GLI
      binding site and results in aberrant cellular localization in transfected cells.
      Moreover, morpholino-knockdown experiments in zebrafish demonstrated that zic3
      mutant mRNA failed to rescue the abnormal phenotype, suggesting a role for the
      novel ZIC3 mutation in heterotaxy syndrome.

PMID- 30120290
TI  - Inflammation is a key contributor to ovarian cancer cell seeding.
AB  - The incidence of ovarian cancer dramatically increases in early menopause but the
      factors contributing to cancer onset are unclear. Most ovarian cancers originate
      in the fallopian tube with subsequent implantation of malignant cells into the
      ovary. However, the events and conditions that lead to cancer cell implantation
      are unknown. To quantify which conditions are conducive to the seeding of cancer
      cells in an immunocompetent mouse model, we surgically implanted mouse ovarian
      cancer cells into the oviducts of syngeneic mice and simulated conditions
      associated with ovulatory wound repair, incessant ovulation, ovarian surface
      scarring, and aging. We found that the dominant site of cancer cell seeding was
      not the ovary but the nearby surgical wound site, which was associated with a
      strong and persistent inflammatory reaction. Conditions in the ovary associated
      with inflammation, such as acute ovulatory wound repair, active healing of the
      scarred ovarian surface, and mouse aging, contributed to increased seeding of the
      cancer cells to the surgical wound site and tissues surrounding the ovary.
      Changes in the ovary not accompanied by inflammation, such as completed ovulatory
      cycles and fully-healed scars on the ovarian surface, did not contribute to
      increased cancer cell seeding. We conclude that inflammation is the most likely
      mechanism by which ovulation and postmenopausal events contribute to the
      increased risk of ovarian cancer.

PMID- 30120292
TI  - Author Correction: Multiomics reveal non-alcoholic fatty liver disease in rats
      following chronic exposure to an ultra-low dose of Roundup herbicide.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has not been fixed in the paper.

PMID- 30120291
TI  - Interaction of septin 7 and DOCK8 in equine lymphocytes reveals novel insights
      into signaling pathways associated with autoimmunity.
AB  - The GTP-binding protein septin 7 is involved in various cellular processes,
      including cytoskeleton organization, migration and the regulation of cell shape.
      Septin 7 function in lymphocytes, however, is poorly characterized. Since the
      intracellular signaling role of septin 7 is dependent on its interaction network,
      interaction proteomics was applied to attain novel knowledge about septin 7
      function in hematopoietic cells. Our previous finding of decreased septin 7
      expression in blood-derived lymphocytes in ERU, a spontaneous animal model for
      autoimmune uveitis in man, extended the role of septin 7 to a potential key
      player in autoimmunity. Here, we revealed novel insights into septin 7 function
      by identification of DOCK8 as an interaction partner in primary blood-derived
      lymphocytes. Since DOCK8 is associated with important immune functions, our
      finding of significantly decreased DOCK8 expression and altered DOCK8 interaction
      network in ERU might explain changes in immune response and shows the
      contribution of DOCK8 in pathomechanisms of spontaneous autoimmune diseases.
      Moreover, our analyses revealed insights in DOCK8 function, by identifying the
      signal transducer ILK as a DOCK8 interactor in lymphocytes. Our finding of the
      enhanced enrichment of ILK in ERU cases indicates a deviant influence of DOCK8 on
      inter- and intracellular signaling in autoimmune disease.

PMID- 30120293
TI  - Improving precision for detecting change in the shape of the cornea in patients
      with keratoconus.
AB  - To investigate a method for precision analysis to discriminate true corneal
      change from measurement imprecision in keratoconus (KC). Thirty patients with KC
      and 30 healthy controls were included. Coefficients of repeatability and limits
      of agreement (LOA) were compared using multiple measurements for inter-observer
      and inter-device agreement with the Pentacam HR, Orbscan IIz, and Tomey Casia SS
      1000. Correlation of repeated measurements was evaluated using a linear mixed
      effect model (also called random effect model). A formula was derived for the
      theoretical expected change in precision and compared with measured change.
      Correlation between measurements from the same eye was small (R = 0.13). The
      99.73% LOA (3 SD) of the mean of three measurements, provided better precision
      than 95% LOA (2 SD) of single cut-off values as expected from statistical theory
      for uncorrelated measurements for evidence of a significant change in corneal
      shape in patients with keratoconus. This enabled the determination of cut-off
      values for the detection of true change in corneal shape. The mean of three
      repeated measurements will provide better precision when there is minimal
      correlation. Three (rather than two) standard deviations provides a precise
      estimate of the LOA within or between observers and can be used as a reliable
      measure for identifying stage-independent corneal shape changes (progression) in
      keratoconus.

PMID- 30120294
TI  - Invisible Flashes Alter Perceived Sound Location.
AB  - Information integration across the senses is fundamental for effective
      interactions with our environment. The extent to which signals from different
      senses can interact in the absence of awareness is controversial. Combining the
      spatial ventriloquist illusion and dynamic continuous flash suppression (dCFS),
      we investigated in a series of two experiments whether visual signals that
      observers do not consciously perceive can influence spatial perception of sounds.
      Importantly, dCFS obliterated visual awareness only on a fraction of trials
      allowing us to compare spatial ventriloquism for physically identical flashes
      that were judged as visible or invisible. Our results show a stronger
      ventriloquist effect for visible than invisible flashes. Critically, a robust
      ventriloquist effect emerged also for invisible flashes even when participants
      were at chance when locating the flash. Collectively, our findings demonstrate
      that signals that we are not aware of in one sensory modality can alter spatial
      perception of signals in another sensory modality.

PMID- 30120295
TI  - Characterization of induced tissue-specific stem cells from pancreas by a
      synthetic self-replicative RNA.
AB  - Induced pluripotent stem (iPS) cells have significant implications for overcoming
      most of the ethical issues associated with embryonic stem (ES) cells.
      Furthermore, our recent study demonstrated the generation of induced tissue
      specific stem (iTS) cells by transient overexpression of the reprogramming
      factors using a plasmid combined with tissue-specific selection. In this study,
      we were able to generate RNA-based iTS cells that utilize a single, synthetic,
      self-replicating VEE-RF RNA replicon expressing four reprogramming factors (OCT4,
      KLF4, SOX2, and GLIS1). A single VEE-RF RNA transfection into mouse pancreatic
      tissue resulted in efficient generation of iTS cells from pancreas (iTS-P cells)
      with genetic markers of endoderm and pancreatic progenitors and differentiation
      into insulin-producing cells more efficiently than ES cells. Subcutaneous
      transplantation of iTS-P cells into immunodeficient mice resulted in no teratoma
      formation. Bisulfite genomic sequencing demonstrated that the promoters of Oct4
      and Nanog remained partially methylated in iTS-P cells. We compared the global
      gene-expression profiles of ES cells, iTS-P cells, and pancreatic islets.
      Microarray analyses confirmed that the iTS-P cells were similar but not identical
      to ES cells compared with islets. These data suggest that iTS-P cells are cells
      that inherit numerous components of epigenetic memory from pancreas cells and
      acquire self-renewal potential. The generation of iTS cells may have important
      implications for the clinical application of stem cells.

PMID- 30120296
TI  - Characterization of the beta-defensin genes in giant panda.
AB  - beta-Defensins are small antimicrobial proteins expressed in various organisms
      and have great potential for improving animal health and selective breeding
      programs. Giant pandas have a distinctive lineage in Carnivora, and it is unclear
      whether beta-defensin genes have experienced different selective pressures during
      giant panda evolution. We therefore characterized the giant panda (Ailuropoda
      melanoleuca) beta-defensin gene family through gap filling, TBLASTN, and HMM
      searches. Among 36 beta-defensins identified, gastrointestinal disease may induce
      the expression of the DEFB1 and DEFB139 genes in the digestive system. Moreover,
      for DEFB139, a significant positive selection different from that of its homologs
      was revealed through branch model comparisons. A Pro-to-Arg mutation in the giant
      panda DEFB139 mature peptide may have enhanced the peptide's antimicrobial
      potency by increasing its stability, isoelectric point, surface charge and
      surface hydrophobicity, and by stabilizing its second beta-sheet. Broth
      microdilution tests showed that the increase in net charge caused by the Pro-to
      Arg mutation has enhanced the peptide's potency against Staphylococcus aureus,
      although the increase was minor. We expect that additional gene function and
      expression studies of the giant panda DEFB139 gene could improve the existing
      conservation strategies for the giant panda.

PMID- 30120298
TI  - Extracellular vesicles protect glucuronidase model enzymes during freeze-drying.
AB  - Extracellular vesicles (EVs) are natural nanoparticles that play important roles
      in intercellular communication and are increasingly studied for biosignalling,
      pathogenesis and therapy. Nevertheless, little is known about optimal conditions
      for their transfer and storage, and the potential impact on preserving EV-loaded
      cargoes. We present the first comprehensive stability assessment of different
      widely available types of EVs during various storage conditions including -80 
      degrees C, 4  degrees C, room temperature, and freeze-drying (lyophilisation).
      Lyophilisation of EVs would allow easy handling at room temperature and thus
      significantly enhance their expanded investigation. A model enzyme, beta
      glucuronidase, was loaded into different types of EVs derived from mesenchymal
      stem cells, endothelial cells and cancer cells. Using asymmetric flow field-flow
      fractionation we proved that the model enzyme is indeed stably encapsulated into
      EVs. When assessing enzyme activity as indicator for EV stability, and in
      comparison to liposomes, we show that EVs are intrinsically stable during
      lyophilisation, an effect further enhanced by cryoprotectants. Our findings
      provide new insight for exploring lyophilisation as a novel storage modality and
      we create an important basis for standardised and advanced EV applications in
      biomedical research.

PMID- 30120297
TI  - COMP-Angiopoietin-1 accelerates muscle regeneration through N-cadherin
      activation.
AB  - Angiopoietin-1 modulates vascular stability via Tie2 on endothelial cells. In our
      previous study, we also showed it acts as an inhibitor of cardiomyocyte death.
      However, it remains poorly understood how Ang1 regulates myogenesis during muscle
      regeneration. Here we found that COMP-Ang1 (cAng1) enhances muscle regeneration
      through N-cadherin activation. Muscle fiber regeneration after limb muscle damage
      by ischemic injury was enhanced with cAng1 treatment. Mechanistically cAng1
      directly bound to N-cadherin on the myoblast surface in a Ca2+ dependent manner.
      The interaction enhanced N-cadherin activation via N-cadherin/p120-catenin
      complex formation, which in turn activated p38MAPK (but not AKT or ERK) and
      myogenin expression (but not myoD) as well as increasing myogenin+ cells in/ex
      vivo. After transplantation of GFP-expressing myoblasts (GFP-MB), we showed an
      increased generation of GFP+ myotubes with adenovirus cAng1 (Adv-cAng1)
      injection. Adv-cAng1, however, could not stimulate myotube formation in N
      cadherin-depleted GFP-MB. Taken together, this study uncovers the mechanism of
      how cAng1 promotes myoblast differentiation and muscle regeneration through the N
      cadherin/p120-catenin/p38MAPK/myogenin axis.

PMID- 30120299
TI  - Transcriptional network analysis of human astrocytic endfoot genes reveals region
      specific associations with dementia status and tau pathology.
AB  - The deposition of misfolded proteins, including amyloid beta plaques and
      neurofibrillary tangles is the histopathological hallmark of Alzheimer's disease
      (AD). The glymphatic system, a brain-wide network of perivascular pathways that
      supports interstitial solute clearance, is dependent upon expression of the
      perivascular astroglial water channel aquaporin-4 (AQP4). Impairment of
      glymphatic function in the aging rodent brain is associated with reduced
      perivascular AQP4 localization, and in human subjects, reduced perivascular AQP4
      localization is associated with AD diagnosis and pathology. Using human
      transcriptomic data, we demonstrate that expression of perivascular astroglial
      gene products dystroglycan (DAG1), dystrobrevin (DTNA) and alpha-syntrophin
      (SNTA1), are associated with dementia status and phosphorylated tau (P-tau)
      levels in temporal cortex. Gene correlation analysis reveals altered expression
      of a cluster of potential astrocytic endfoot components in human subjects with
      dementia, with increased expression associated with temporal cortical P-tau
      levels. The association between perivascular astroglial gene products, including
      DTNA and megalencephalic leukoencephalopathy with subcortical cysts 1 (MLC1) with
      AD status was confirmed in a second human transcriptomic dataset and in human
      autopsy tissue by Western blot. This suggests changes in the astroglial endfoot
      domain may underlie vulnerability to protein aggregation in AD.

PMID- 30120300
TI  - Confirmation of GLRA3 as a susceptibility locus for albuminuria in Finnish
      patients with type 1 diabetes.
AB  - Urinary albumin excretion is an early sign of diabetic kidney disease, affecting
      every third individual with diabetes. Despite substantial estimated heritability,
      only variants in the GLRA3 gene have been genome-wide significantly associated (p
      value < 5 * 10-8) with diabetic albuminuria, in Finnish individuals with type 1
      diabetes; However, replication attempt in non-Finnish Europeans with type 1
      diabetes showed nominally significant association in the opposite direction,
      suggesting a population-specific effect, but simultaneously leaving the finding
      controversial. In this study, the association between the common rs10011025
      variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent
      Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all
      Finnish individuals yielded a genome-wide significant association. The
      association was particularly pronounced in subjects not reaching the treatment
      target for blood glucose levels (HbA1c > 7%; N = 2560, p = 1.7 * 10-9). Even
      though further studies are needed to pinpoint the causal variants, dissecting the
      association at the GLRA3 locus may uncover novel molecular mechanisms for
      diabetic albuminuria irrespective of population background.

PMID- 30120302
TI  - FN400 amplitudes reveal the differentiation of semantic inferences within natural
      vs. artificial domains.
AB  - Category-based inferences allow inductions about novel properties based on
      categorical memberships (e.g., knowing all trout have genes [premise] allows us
      to infer that all fish have genes [conclusion]). Natural (N) and artificial (A)
      domains are the most obvious and traditional distinctions in categorization. The
      distinct event-related potential (ERP) responses for N and A domains have not yet
      been examined during category-based inferences. In this study, the differences
      between ERP inference parameters within N and A domains were measured during
      inductive decision processing, while controlling the premise-conclusion
      similarity and premise typicality between those two domains. Twenty-two adults
      were asked to make a decision on whether a conclusion was definitely weak,
      possibly weak, possibly strong, or definitely strong, based on a premise. The
      behavioral results showed that semantic inferences within the N domain shared
      similar inductive strength, similar "correct" response rates, and similar
      reaction times with that within the A domain. However, the ERP results showed
      that semantic inferences elicited smaller frontal-distributed N400 (FN400)
      amplitudes within the N domain than within the A domain, which suggested that
      knowledge of the ontological domain of a category affects category-based
      inferences, and underlaid the increased categorical coherence and homogeneity in
      the N as compared to the A categories. Therefore, we have distinguished the
      cognitive course of semantic inferences between N and A domains.

PMID- 30120303
TI  - Humpback whale migrations to Antarctic summer foraging grounds through the
      southwest Pacific Ocean.
AB  - Humpback whale (Megaptera novaeangliae) populations typically undertake seasonal
      migrations, spending winters in low latitude breeding grounds and summers
      foraging in high latitude feeding grounds. Until recently, a broad scale
      understanding of whale movement has been derived from whaling records, Discovery
      marks, photo identification and genetic analyses. However, with advances in
      satellite tagging technology and concurrent development of analytical
      methodologies we can now detail finer scale humpback whale movement, infer
      behavioural context and examine how these animals interact with their physical
      environment. Here we describe the temporal and spatial characteristics of
      migration along the east Australian seaboard and into the Southern Ocean by 30
      humpback whales satellite tagged over three consecutive austral summers. We
      characterise the putative Antarctic feeding grounds and identify supplemental
      foraging within temperate, migratory corridors. We demonstrate that Antarctic
      foraging habitat is associated with the marginal ice zone, with key predictors of
      inferred foraging behaviour including distance from the ice edge, ice melt rate
      and variability in ice concentration two months prior to arrival. We discuss the
      highly variable ice season within the putative foraging habitat and the
      implications that this and other environmental factors may have on the continued
      strong recovery of this humpback whale population.

PMID- 30120301
TI  - Linear and Volumetric Mandibular Asymmetries in Adult Patients With Different
      Skeletal Classes and Vertical Patterns: A Cone-Beam Computed Tomography Study.
AB  - This study aimed to quantify the height of the mandibular condyle and ramus,
      condylar volume, and the asymmetry index in adult patients of different sex,
      skeletal class and vertical pattern using Cone-Beam Computed Tomography (CBCT),
      and to determine whether there were differences between these groups. The study
      used CBCT scans of 159 patients with a mean age of 32.32 +/- 8.31 years.
      InVivoDental(r) software was used to perform both linear (condylar, ramal, and
      total height) and condylar volume measurements. Linear and volumetric asymmetries
      were calculated. There were not significant differences between right and left
      sides. The mean value obtained for condyle height was 7.27 mm, ramus height 42.3
      mm, total height 49.6 mm and condyle volume 1907.1 mm3, with significant
      differences between men and women. Significantly higher values were found for
      condylar volume in hypodivergent patterns (p = 0.001) and for the asymmetry index
      of the condylar volume in Class II patients (p < 0.05). The prevalence of
      relevant asymmetry was high for condyle height and volume (73.1% y 75.6%
      respectively). Higher height and volume values were found among men, Class III,
      and hypodivergent patients. Linear and volumetric asymmetries were more prevalent
      among men, Class III and hyperdivergent patterns.

PMID- 30120304
TI  - Social bees are fitter in more biodiverse environments.
AB  - Bee population declines are often linked to human impacts, especially habitat and
      biodiversity loss, but empirical evidence is lacking. To clarify the link between
      biodiversity loss and bee decline, we examined how floral diversity affects
      (reproductive) fitness and population growth of a social stingless bee. For the
      first time, we related available resource diversity and abundance to resource
      (quality and quantity) intake and colony reproduction, over more than two years.
      Our results reveal plant diversity as key driver of bee fitness. Social bee
      colonies were fitter and their populations grew faster in more florally diverse
      environments due to a continuous supply of food resources. Colonies responded to
      high plant diversity with increased resource intake and colony food stores. Our
      findings thus point to biodiversity loss as main reason for the observed bee
      decline.

PMID- 30120306
TI  - Arbitrary shaped beam scattering from a chiral-coated conducting object with
      arbitrary monochromatic illumination.
AB  - An exact semi-analytical method of calculating the scattered fields from a chiral
      coated conducting object under arbitrary shaped beam illumination is developed.
      The scattered fields and the fields within the chiral coating are expanded in
      terms of appropriate spherical vector wave functions. The unknown expansion
      coefficients are determined by solving an infinite system of linear equations
      derived using the method of moments technique and the boundary conditions. For
      incidence of a Gaussian beam, circularly polarized wave, zero-order Bessel beam
      and Hertzian electric dipole radiation on a chiral-coated conducting spheroid and
      a chiral-coated conducting circular cylinder of finite length, the normalized
      differential scattering cross sections are evaluated and discussed briefly.

PMID- 30120305
TI  - Including planocerid flatworms in the diet effectively toxifies the pufferfish,
      Takifugu niphobles.
AB  - Beginning with the larval stages, marine pufferfish such as Takifugu niphobles
      contain tetrodotoxin (TTX), an extremely potent neurotoxin. Although highly
      concentrated TTX has been detected in adults and juveniles of these fish, the
      source of the toxin has remained unclear. Here we show that TTX in the flatworm
      Planocera multitentaculata contributes to the toxification of the pufferfish
      throughout the life cycle of the flatworm. A species-specific PCR method was
      developed for the flatworm, and the specific DNA fragment was detected in the
      digesta of wild pufferfish adults. Predation experiments showed that flatworm
      larvae were eaten by the pufferfish juveniles, and that the two-day postprandial
      TTX content in these pufferfish was 20-50 MUg/g. Predation experiments
      additionally showed flatworm adults were also eaten by pufferfish young, and
      after two days of feeding, TTX accumulated in the skin, liver and intestine of
      the pufferfish.

PMID- 30120307
TI  - Mechanistic role of transglutaminase-2 in focal adhesions.
AB  - Transglutaminase (TG)-2 interacts with matrix proteins and integrins, forming
      focal adhesions (FA) to initiate cell migration, thus playing a vital role in
      wound healing. Previously we showed that TG-2 influenced phosphorylation of
      paxillin and other FA proteins. Here, we aimed to investigate the molecular
      mechanism of TG-2 regulation of paxillin. Human corneal epithelial cells
      expressing shRNA against TG-2 (shTG) and scrambled sequence control (shRNA) were
      cultured. TG-2 was pulled down by anti-paxillin antibody, but not MAP3K12. Cell
      free interaction assay with immobilized paxillin shows that TG-2 bind to paxillin
      directly. JNK was the strongest kinase for paxillin phosphorylation in the in
      vitro kinase screen, but TG-2 could not phosphorylate paxillin directly.
      Increasing TG-2 concentrations did not increase the amount of JNK in the TG
      2/paxillin complex. Immunofluoresent staining shows that TG-2 colocalises with
      vinculin and paxillin in FA of migrating cells. TG-2 binds to paxillin and JNK
      containing FA but does not recruit JNK directly. Taken together with previous
      findings, TG-2 binds paxillin non-covalently, and JNK can phosphorylate paxillin,
      these processes critically regulate corneal epithelial adhesion and migration.

PMID- 30120308
TI  - Towards the geometric structure of small supported Au9 clusters on Si.
AB  - Ultra-small clusters containing few atoms are of high interest in both
      fundamental research and applications due to their specific functional, magnetic
      or chemical properties which depend on size and composition. The experimental
      results of the morphology of the size-selected clusters, consisting of few atoms
      can be an ideal benchmark for sophisticated theoretical models. With this
      motivation we have investigated the geometrical structure of mass-selected Au9
      clusters deposited on a silicon substrate prepared by soft-landing conditions. We
      present results obtained experimentally by Grazing-Incidence Small-Angle X-ray
      Scattering (GISAXS). Considering the ultra-small size of the clusters and small
      quantities of material on the surface, we combined advanced techniques which
      allowed us to investigate the surface structure of the sample. The resulting
      structural sizes are in concordance with cluster theory. Using a model-based
      approach, the advanced X-ray techniques allow for understanding how to resolve
      the possible cluster structure, identify optimal experimental conditions and
      obtain the probable morphological information which is challenging to be obtained
      otherwise.

PMID- 30120309
TI  - Hyperuricemia is associated with atrial fibrillation prevalence in very elderly -
      a community based study in Chengdu, China.
AB  - Hyperuricemia is a risk factor for cardiovascular diseases. However, in very
      elderly, the relationship between hyperuricemia and the prevalence of atrial
      fibrillation (AF) is not clear. This study aimed to investigate hyperuricemia and
      the risk of AF in community very elderly. In this cross-sectional study, 1056
      very elderly in community were enrolled. Serum uric acid (SUA) were measured and
      rest 12-lead electrocardiogram was performed. Multiple logistic regression models
      were used to explore risk factors for AF in very elderly. Finally, 1038
      participants were included in analysis and the mean age of the study participants
      were 83.6 +/- 3.4 years (age range 80-100 years). The mean SUA level was 350.1 +/
      84.5 umol/L. The estimated prevalence of AF was 5.3%, and there was no
      significant sex difference (5.8% for men and 4.8% for women, p = 0.401). Multiple
      logistic regression found that participants with hyperuricemia (SUA >416 umol/L
      in men and >357 umol/L in women) had a higher risk (odds ratio: 2.080, 95%
      confidence interval: 1.103-4.202, P = 0.007) of suffering AF in very elderly
      Chinese. In conclusion, AF is relatively frequent in this community very elderly
      Chinese in Chengdu. Hyperuricemia is associated with the prevalence of AF in
      general very elderly.

PMID- 30120310
TI  - Fused silica optical fibers with graded index nanostructured core.
AB  - The ability to shape the index profile of optical fibers holds the key to fully
      flexible engineering of their optical properties and future applications. We
      present a new approach for the development of a graded index fused silica fiber
      based on core nanostructurization. A graded index core is obtained by means of
      distribution of two types of subwavelength glass rods. The proposed method allows
      to obtain arbitrary graded distribution not limited to the circular or any other
      symmetry, such as in the standard graded index fibers. We have developed a proof
      of concept fiber with parabolic refractive index core and showed a perfect match
      between its predicted, designed and measured properties. The fiber has a core
      composed of 2107 rods of 190 nm of diameter made of either pure fused silica or
      Ge-doped fused silica with 8.5% mol concentration. The proposed method breaks the
      limits of standard fabrication approaches used in fused silica fiber technology.

PMID- 30120311
TI  - Hsa-miR-10a-5p downregulation in mutant UQCRB-expressing cells promotes the
      cholesterol biosynthesis pathway.
AB  - Ubiquinol cytochrome c reductase binding protein (UQCRB) is known to play crucial
      roles in the development of various types of diseases. However, the link between
      UQCRB and microRNAs remains unknown. In the present study, we performed microRNA
      sequencing of mutant UQCRB-expressing stable cell lines that exhibited pro
      oncogenic activities caused by expression of the mutant UQCRB gene. Results
      showed that hsa-miR-10a-5p was significantly downregulated in the mutant UQCRB
      expressing cell lines. Furthermore, mRNA sequencing and gene ontology analysis of
      differentially expressed genes (DEGs) revealed that the cholesterol biosynthesis
      pathway might be activation by mutant UQCRB expression. Moreover, inhibition of
      cholesterol synthesis in mutant UQCRB-expressing cells via treatment with the
      specific inhibitors suppressed the cell proliferation. Transfection with a hsa
      miR-10a-5p mimic validated that lanosterol synthase (LSS) is a target of hsa-miR
      10a-5p. In addition, hsa-miR-10a-5p was found to be downregulated in liver cancer
      cell lines overexpressing UQCRB. Taken together, our findings highlighted the
      potential use of hsa-miR-10a-5p as a biomarker for UQCRB related diseases.

PMID- 30120312
TI  - The prognostic significance of Albumin-to-Alkaline Phosphatase Ratio in upper
      tract urothelial carcinoma.
AB  - To assess the prognostic impact of pretreatment albumin-to-alkaline phosphatase
      ratio (AAPR) in patients with upper tract urothelial carcinoma (UTUC), the data
      of 692 patients, operated between 2003 and 2016 in our center, were
      retrospectively assessed. The threshold of AAPR was defined as 0.58 by using the
      receiver-operating curve analysis. Overall survival (OS), cancer-specific
      survival (CSS), and recurrence-free survival (RFS) were evaluated using the
      Kaplan-Meier method. And the univariate and multivariate Cox's regression models
      were performed to identify independent prognostic predictors. The results showed
      that AAPR <0.58 was significantly related to higher pT stage and grade,
      concomitant variant histology, anemia and larger tumor size. Additionally,
      patients with a lower AAPR had an inferior survival outcomes than those with an
      AAPR >=0.58 (all P < 0.001). Multivariate analysis suggested that the lower AAPR
      was also an independent risk factor for poor OS (HR 1.587, 95%CI: 1.185-2.126; P
      = 0.002), CSS (HR 1.746, 95%CI: 1.249-2.440; P = 0.001), and RFS (HR 1.337,
      95%CI: 1.027-1.739; P = 0.031). Moreover, subgroup analysis demonstrated the
      lower AAPR was related to worse prognosis in high-grade UTUC patients; but in
      those with low-grade disease, no relationship between them was observed. In
      conclusion, our results found that the decreased AAPR was independently related
      to poor survival outcomes in UTUC patients. Using the AAPR for subclassification
      of high-grade UTUC seems to further identify a poor prognostic group and
      contribute to clinical decisions making.

PMID- 30120313
TI  - Neck-specific exercise may reduce radiating pain and signs of neurological
      deficits in chronic whiplash - Analyses of a randomized clinical trial.
AB  - Up to 90% of people with neurological deficits following a whiplash injury do not
      recover and cervical muscle dysfunction is common. The aim of this multicentre,
      randomized controlled trial was to examine whether two versions of neck-specific
      exercise or prescription of physical activity (PPA) can improve radiating arm
      pain and clinical signs that can be associated with neurological deficits in
      people with chronic whiplash associated disorders (WAD). Participants with
      chronic WAD, arm symptoms and signs associated with neurological deficits (n =
      171) were randomized to: 12 weeks of neck-specific exercise without (NSE) or with
      a behavioural approach (NSEB), or PPA. Pain/bothersomeness frequency, six
      measures of arm pain/paraesthesia (VAS scales), and four clinical neurological
      tests were evaluated after 3 months. The NSE group reported the lowest frequency
      and lowest levels of arm pain, the highest proportion of participants with at
      least 50% pain reduction and the highest proportion of normal arm muscle force.
      The NSEB group reported increased normal tendon reflexes. No improvements were
      recorded for the PPA group. Neck-specific exercise may improve arm pain and
      decrease signs of neurological deficits, but the addition of a behavioural
      approach does not seem to be of additional benefit.

PMID- 30120314
TI  - Automatic hyoid bone detection in fluoroscopic images using deep learning.
AB  - The displacement of the hyoid bone is one of the key components evaluated in the
      swallow study, as its motion during swallowing is related to overall swallowing
      integrity. In daily research settings, experts visually detect the hyoid bone in
      the video frames and manually plot hyoid bone position frame by frame. This study
      aims to develop an automatic method to localize the location of the hyoid bone in
      the video sequence. To automatically detect the location of the hyoid bone in a
      frame, we proposed a single shot multibox detector, a deep convolutional neural
      network, which is employed to detect and classify the location of the hyoid bone.
      We also evaluated the performance of two other state-of-art detection methods for
      comparison. The experimental results clearly showed that the single shot multibox
      detector can detect the hyoid bone with an average precision of 89.14% and
      outperform other auto-detection algorithms. We conclude that this automatic hyoid
      bone tracking system is accurate enough to be widely applied as a pre-processing
      step for image processing in dysphagia research, as well as a promising
      development that may be useful in the diagnosis of dysphagia.

PMID- 30120316
TI  - Hybrid optical-electronic convolutional neural networks with optimized
      diffractive optics for image classification.
AB  - Convolutional neural networks (CNNs) excel in a wide variety of computer vision
      applications, but their high performance also comes at a high computational cost.
      Despite efforts to increase efficiency both algorithmically and with specialized
      hardware, it remains difficult to deploy CNNs in embedded systems due to tight
      power budgets. Here we explore a complementary strategy that incorporates a layer
      of optical computing prior to electronic computing, improving performance on
      image classification tasks while adding minimal electronic computational cost or
      processing time. We propose a design for an optical convolutional layer based on
      an optimized diffractive optical element and test our design in two simulations:
      a learned optical correlator and an optoelectronic two-layer CNN. We demonstrate
      in simulation and with an optical prototype that the classification accuracies of
      our optical systems rival those of the analogous electronic implementations,
      while providing substantial savings on computational cost.

PMID- 30120315
TI  - Assessing animal affect: an automated and self-initiated judgement bias task
      based on natural investigative behaviour.
AB  - Scientific methods for assessing animal affect, especially affective valence
      (positivity or negativity), allow us to evaluate animal welfare and the
      effectiveness of 3Rs Refinements designed to improve wellbeing. Judgement bias
      tasks measure valence; however, task-training may be lengthy and/or require
      significant time from researchers. Here we develop an automated and self
      initiated judgement bias task for rats which capitalises on their natural
      investigative behaviour. Rats insert their noses into a food trough to start
      trials. They then hear a tone and learn either to stay for 2 s to receive a food
      reward or to withdraw promptly to avoid an air-puff. Which contingency applies is
      signalled by two different tones. Judgement bias is measured by responses to
      intermediate ambiguous tones. In two experiments we show that rats learn the task
      in fewer sessions than other automated variants, generalise responses across
      ambiguous tones as expected, self-initiate 4-5 trials/min, and can be tested
      repeatedly. Affect manipulations generate main effect trends in the predicted
      directions, although not localised to ambiguous tones, so further construct
      validation is required. We also find that tone-reinforcer pairings and
      reinforcement or non-reinforcement of ambiguous trials can affect responses to
      ambiguity. This translatable task should facilitate more widespread uptake of
      judgement bias testing.

PMID- 30120317
TI  - Publisher Correction: The ciliopathy protein TALPID3/KIAA0586 acts upstream of
      Rab8 activation in zebrafish photoreceptor outer segment formation and
      maintenance.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30120319
TI  - Augmentation of leaf color parameters, pigments, vitamins, phenolic acids,
      flavonoids and antioxidant activity in selected Amaranthus tricolor under
      salinity stress.
AB  - Amaranthus tricolor genotype VA13 was evaluated under four salinity stress in
      terms of color parameters, leaf pigments, beta-carotene, vitamin C, TPC, TFC,
      TAC, phenolic acids and flavonoids. Salinity stress significantly increases all
      the studied traits. The increments of all these compounds were high under
      moderate and severe salinity stress compared to control condition. In this study,
      trans-cinnamic acid was newly identified phenoic acid in A. tricolor. Salicylic
      acid, vanilic acid, trans-cinnamic acid, gallic acid, chlorogenic acid, rutin,
      isoquercetin and m-coumaric acid were the most abundant phenolic compounds of
      amaranth that increased with the severity of salinity stress. A. tricolor leaves
      are good source of pigments, beta-carotene, vitamin C, bioactive compounds,
      phenolic acids, flavonoids and antioxidants. In salt-stressed amaranth,
      correlation studies revealed strong antioxidant activity of leaf pigments, beta
      carotene, vitamin C, TPC, TFC. These bioactive compounds played a vital role in
      scavenging ROS and could be beneficial to human nutrition by serving as a good
      antioxidant and antiaging source in human health benefit. A. tricolor cultivated
      under salinity stress conditions can contribute a high quality of the final
      product in terms of leaf pigments, bioactive compounds, phenolic acids,
      flavonoids and antioxidants. It can be a promising alternative crop in saline
      prone areas.

PMID- 30120318
TI  - Phospholipidome of endothelial cells shows a different adaptation response upon
      oxidative, glycative and lipoxidative stress.
AB  - Endothelial dysfunction has been widely associated with oxidative stress,
      glucotoxicity and lipotoxicity and underlies the development of cardiovascular
      diseases (CVDs), atherosclerosis and diabetes. In such pathological conditions,
      lipids are emerging as mediators of signalling pathways evoking key cellular
      responses as expression of proinflammatory genes, proliferation and apoptosis.
      Hence, the assessment of lipid profiles in endothelial cells (EC) can provide
      valuable information on the molecular alterations underlying CVDs,
      atherosclerosis and diabetes. We performed a lipidomic approach based on
      hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC
      MS/MS) for the analysis of the phospholipidome of bovine aortic EC (BAEC) exposed
      to oxidative (H2O2), glycative (glucose), or lipoxidative (4-hydroxynonenal, HNE)
      stress. The phospholipid (PL) profile was evaluated for the classes PC, PE, PS,
      PG, PI, SM, LPC and CL. H2O2 induced a more acute adaptation of the PL profile
      than glucose or HNE. Unsaturated PL molecular species were up-regulated after 24
      h incubation with H2O2, while an opposite trend was observed in glucose- and HNE
      treated cells. This study compared, for the first time, the adaptation of the
      phospholipidome of BAEC upon different induced biochemical stresses. Although
      further biological studies will be necessary, our results unveil specific lipid
      signatures in response to characteristic types of stress.

PMID- 30120320
TI  - Klebsiella oxytoca expands in cancer cachexia and acts as a gut pathobiont
      contributing to intestinal dysfunction.
AB  - Cancer cachexia is a complex multi-organ syndrome characterized by body weight
      loss, weakness, muscle atrophy and fat depletion. With a prevalence of 1 million
      people in Europe and only limited therapeutic options, there is a high medical
      need for new approaches to treat cachexia. Our latest results highlighted
      microbial dysbiosis, characterized by a bloom in Enterobacteriaceae and altered
      gut barrier function in preclinical models of cancer cachexia. They also
      demonstrated the potential of targeting the gut microbial dysbiosis in this
      pathology. However, the exact mechanisms underlying the gut microbiota-host
      crosstalk in cancer cachexia remain elusive. In this set of studies, we
      identified Klebsiella oxytoca as one of the main Enterobacteriaceae species
      increased in cancer cachexia and we demonstrated that this bacteria acts as a gut
      pathobiont by altering gut barrier function in cachectic mice. Moreover, we
      propose a conceptual framework for the lower colonization resistance to K.
      oxytoca in cancer cachexia that involves altered host gut epithelial metabolism
      and host-derived nitrate boosting the growth of the gut pathobiont. This set of
      studies constitutes a strong progression in the field of gut microbiota in cancer
      cachexia, by dissecting the mechanism of emergence of one bacterium, K. oxytoca,
      and establishing its role as a gut pathobiont in this severe disease.

PMID- 30120321
TI  - High expression of EZH2 as a marker for the differential diagnosis of malignant
      and benign myogenic tumors.
AB  - Overlap in morphologic features between malignant and benign myogenic tumors,
      such as leiomyosarcoma (LMS) vs. leiomyoma as well as rhabdomyosarcoma (RMS) vs.
      rhabdomyoma, often makes differential diagnosis difficult and challenging. Here
      the expressions of Enhancer of Zeste Homolog 2 (EZH2), Suppressor of Zeste 12
      (SUZ12), retinoblastoma protein associated protein 46 (RbAp46), Embryonic
      Ectoderm Development (EED) and ki-67 protein were detected by
      immunohistochemistry to evaluate their values in differential diagnosis. The
      expression of EZH2 mRNA was investigated by analyzing the Gene Expression Omnibus
      Datasets. The results demonstrated that EZH2 protein was detected in 81.25%
      (26/32) of LMS and 70.58% (36/51) of RMS, whereas none of leiomyoma (n = 16),
      rhabdomyoma (n = 15) and normal tissues (n = 31) showed positive immunostaining
      (p < 0.05). EZH2 protein was found to have a sensitivity of 91.30% and
      specificity of 100% in distinguishing well-differentiated LMS from cellular
      leiomyoma, and a sensitivity of 92.86% and specificity of 100% in distinguishing
      well-differentiated embryonal rhabdomyosarcoma (ERMS) from fetal rhabdomyoma.
      Besides, the expression of EZH2 mRNA was higher in LMS and RMS than in benign
      tumors (p < 0.05). The expressions of SUZ12 and RbAp46 protein were higher in RMS
      than in rhabdomyoma (p < 0.05). Conclusively, the high expression of EZH2 is a
      promising marker in distinguishing well-differentiated LMS from cellular
      leiomyoma, or well-differentiated ERMS from fetal rhabdomyoma, and the
      upregulation of EZH2 protein expression may occur at transcriptional level.

PMID- 30120322
TI  - Detoxification mechanisms involved in ivermectin resistance in the cattle tick,
      Rhipicephalus (Boophilus) microplus.
AB  - The cattle tick Rhipicephalus microplus is one of the most important
      ectoparasites with great sanitary and economic impact for cattle rearing
      worldwide. Ivermectin is commonly used to control tick populations, but its use
      over the last 30 years has led to the development of resistant populations of R.
      microplus, and a concomitant loss of efficacy. In this context, we aimed to
      determine the metabolic mechanisms that contribute to ivermectin resistance in a
      resistant strain of this species. We performed lethal time bioassays with
      inhibitors of detoxifying enzymes and xenobiotic transporters (four
      detoxification pathways) using two strains of ticks: a susceptible strain, Mozo,
      and a resistant strain, Juarez. We used four inhibitors to test the involvement
      of different families of proteins responsible for detoxification of ivermectin,
      namely cytochrome P450, esterases, glutathione-S-transferase, and ATP Binding
      Cassette Transporters. We calculated the synergistic factor for each inhibitor
      and strain. To different degrees, all tested inhibitors altered the mortality
      rates in the strain Juarez, indicating that multiple mechanisms are responsible
      for the resistant phenotype. Detoxification mechanisms mediated by ABC
      transporters were observed to be the most important. Esterases, glutathione-S
      transferases, and cytochrome-oxidases played less important roles in
      detoxification.

PMID- 30120323
TI  - Atomic number dependence of Z contrast in scanning transmission electron
      microscopy.
AB  - Annular dark-field (ADF) imaging by scanning transmission electron microscopy
      (STEM) is a common technique for material characterization with high spatial
      resolution. It has been reported that ADF signal is proportional to the nth power
      of the atomic number Z, i.e., the Z contrast in textbooks and papers. Here we
      first demonstrate the deviation from the power-law model by quantitative
      experiments of a few 2D materials (graphene, MoS2 and WS2 monolayers). Then we
      elucidate ADF signal of single atoms using simulations to clarify the cause of
      the deviation. Two major causes of the deviation from the power-law model will be
      pointed out. The present study provides a practical guideline for the usage of
      the conventional power-law model for ADF imaging.

PMID- 30120324
TI  - Antibodies against adenovirus fiber and penton base proteins inhibit adenovirus
      vector-mediated transduction in the liver following systemic administration.
AB  - Pre-existing anti-adenovirus (Ad) neutralizing antibodies (AdNAbs) are a major
      barrier in clinical gene therapy using Ad vectors and oncolytic Ads; however, it
      has not been fully elucidated which Ad capsid protein-specific antibodies are
      involved in AdNAb-mediated inhibition of Ad infection in vivo. In this study,
      mice possessing antibodies specific for each Ad capsid protein were prepared by
      intramuscular electroporation of each Ad capsid protein-expressing plasmid. Ad
      vector-mediated hepatic transduction was efficiently inhibited by more than 100
      fold in mice immunized with a fiber protein-expressing plasmid or a penton base
      expressing plasmid. An Ad vector pre-coated with FX before administration
      mediated more than 100-fold lower transduction efficiencies in the liver of
      warfarinized mice immunized with a fiber protein-expressing plasmid or a penton
      base-expressing plasmid, compared with those in the liver of warfarinized non
      immunized mice. These data suggest that anti-fiber protein and anti-penton base
      antibodies bind to an Ad vector even though FX has already bound to the hexon,
      and inhibit Ad vector-mediated transduction. This study provides important clues
      for the development of a novel Ad vector that can circumvent inhibition with
      AdNAbs.

PMID- 30120325
TI  - Multicilin and activated E2f4 induce multiciliated cell differentiation in
      primary fibroblasts.
AB  - Multiciliated cells (MCCs) are specialized epithelial cells that project hundreds
      of motile cilia. To form these cilia, MCCs differentiate by dramatically
      expanding centriole number, using assembly factors required for centriole
      duplication during the cell cycle and multiple, novel assembly sites, called the
      deuterosome. The small coiled-coil protein, Multicilin, acting in a complex with
      the E2F proteins can initiate multiciliated cell differentiation, but reportedly
      only in a limited range of epithelial progenitors. To examine the nature of this
      restricted activity, we analyzed Multicilin activity in primary mouse embryonic
      fibroblasts (MEFs), a cell type distant from the epithelial lineages where MCCs
      normally arise. We show that Multicilin transcriptional activity is markedly
      attenuated in MEFs, where it induces only limited centriole expansion in a small
      fraction of cells. We further show that this transcriptional block is largely
      bypassed by expressing Multicilin along with a form of E2f4 where a generic
      activation domain from HSV1 VP16 (E2f4VP16) is fused to the carboxy terminus.
      MEFs respond to Multicilin and E2f4VP16 by undergoing massive centriole expansion
      via the deuterosome pathway, recapitulating a temporal sequence of organelle
      biogenesis that occurs in epithelial progenitors during MCC differentiation.
      These results suggest that the pattern of organelle biogenesis occurring in
      differentiating MCCs is largely determined by the transcriptional changes induced
      by Multicilin.

PMID- 30120326
TI  - Oral Delivery of a DNA Vaccine Expressing the PrM and E Genes: A Promising
      Vaccine Strategy against Flavivirus in Ducks.
AB  - A flavivirus, named duck tembusu virus (DTMUV), emerged in China in 2010. This
      virus has caused great economic losses in the poultry industry in China and may
      pose a threat to public health. As a safe, efficient and convenient vaccine
      development strategy, DNA-based vaccines have become a popular approach for both
      human and veterinary applications. Attenuated bacteria have been widely used as
      vehicles to deliver heterologous antigens to the immune system. Thus, an
      efficient and low-cost oral delivery DNA vaccine SL7207 (pVAX1-SME) based on
      envelope proteins (prM and E) of DTMUV and attenuated Salmonella typhimurium aroA
      strain SL7207 was developed and evaluated in this study. The prM and E antigen
      proteins were successfully expressed from the vaccine SL7207 (pVAX1-SME) both in
      vitro and in vivo. High titers of the specific antibody against the DTMUV-E
      protein and the neutralizing antibody against the DTMUV virus were both detected
      after vaccination with SL7207 (pVAX1-SME). Ducks orally vaccinated with the
      SL7207 (pVAX-SME) vaccine were efficiently protected from lethal DTMUV infection
      in this study. Taken together, we demonstrated that prM and E proteins of DTMUV
      possess strong immunogenicity against the DTMUV infection. Moreover, an oral
      delivery of the DNA vaccine SL7207 (pVAX1-SME) utilizing Salmonella SL7207 was an
      efficient way to protect the ducks against DTMUV infection and provides an
      economic and fast vaccine delivery strategy for a large-scale clinical use.

PMID- 30120328
TI  - Immuno-impedimetric Biosensor for Onsite Monitoring of Ascospores and Forecasting
      of Sclerotinia Stem Rot of Canola.
AB  - Sclerotinia stem rot, caused by the fungal pathogen Sclerotinia sclerotiorum, is
      a destructive disease of canola and many other broadleaf crops. The primary
      inoculum responsible for initiating Sclerotinia epidemics is airborne ascospores
      released from the apothecia of sclerotia. Timely detection of the presence of
      airborne ascospores can serve as an early-warning system for forecasting and
      management of the disease. A major challenge is to develop a portable and
      automated device which can be deployed onsite to detect and quantify the presence
      of minute quantities of ascospores in the air and serves as a unit in a network
      of systems for forecasting of the epidemic. In this communication, we present the
      development of an impedimetric non-Faradaic biosensor based on anti-S.
      sclerotiorum polyclonal antibodies as probes to selectively capture the
      ascospores and sense their binding by an impedance based interdigitated electrode
      which was found to directly and unambiguously correlate the number of ascospores
      on sensor surface with the impedance response.

PMID- 30120329
TI  - Carrier transfer efficiency and its influence on emission properties of telecom
      wavelength InP-based quantum dot - quantum well structures.
AB  - We investigate a hybrid system containing an In0.53Ga0.47As quantum well (QW),
      separated by a thin 2 nm In0.53Ga0.23Al0.24As barrier from 1.55 um emitting InAs
      quantum dots (QDs), grown by molecular beam epitaxy on an InP substrate.
      Photoreflectance and photoluminescence (PL) spectroscopies are used to identify
      optical transitions in the system, with support of 8-band kp modelling. The main
      part of the work constitute the measurements and analysis of thermal quenching of
      PL for a set of samples with different QW widths (3-6 nm). Basing on Arrhenius
      plots, carrier escape channels from the dots are identified, pointing at the
      importance of carrier escape into the QW. A simple two level rate equations model
      is proposed and solved, exhibiting qualitative agreement with experimental
      observations. We show that for a narrow QW the escape process is less efficient
      than carrier supply via the QW due to the narrow barrier, resulting in improved
      emission intensity at room temperature. It proves that with carefully designed
      energy level structure, a hybrid QW/QD system can be used as an active region in
      telecom lasers with improved efficiencies.

PMID- 30120327
TI  - Analyses of the three 1-Cys Peroxiredoxins from Aspergillus fumigatus reveal that
      cytosolic Prx1 is central to H2O2 metabolism and virulence.
AB  - Standing among the front defense strategies against pathogens, host phagocytic
      cells release various oxidants. Therefore, pathogens have to cope with stressful
      conditions at the site of infection. Peroxiredoxins (Prx) are highly reactive and
      abundant peroxidases that can support virulence and persistence of pathogens in
      distinct hosts. Here, we revealed that the opportunistic human pathogen A.
      fumigatus presents three 1-Cys Prx (Prx6 subfamily), which is unprecedented. We
      showed that PrxB and PrxC were in mitochondria, while Prx1 was in cytosol. As
      observed for other Prxs, recombinant Prx1 and PrxC decomposed H2O2 at elevated
      velocities (rate constants in the 107 M-1s-1 range). Deletion mutants for each
      Prx displayed higher sensitivity to oxidative challenge in comparison with the
      wild-type strain. Additionally, cytosolic Prx1 was important for A. fumigatus
      survival upon electron transport dysfunction. Expression of Prxs was dependent on
      the SakAHOG1 MAP kinase and the Yap1YAP1 transcription factor, a global regulator
      of the oxidative stress response in fungi. Finally, cytosolic Prx1 played a major
      role in pathogenicity, since it is required for full virulence, using a
      neutropenic mouse infection model. Our data indicate that the three 1-Cys Prxs
      act together to maintain the redox balance of A. fumigatus.

PMID- 30120330
TI  - Effect of probiotic Bifidobacterium bifidum G9-1 on the relationship between gut
      microbiota profile and stress sensitivity in maternally separated rats.
AB  - Although gut microbiota and early life events are likely involved in the
      development of irritable bowel syndrome (IBS), it remains unclear how these
      factors interact in the pathophysiology of IBS. In the present study, using rats
      subjected to maternal separation (MS) as a model of IBS, we investigated
      interrelationships among gut microbiota, stress susceptibility and intestinal
      permeability, and examined the effect of the probiotic Bifidobacterium bifidum G9
      1 (BBG9-1) on those interrelationships. When compared with the controls at
      postnatal day 20, MS rats showed hypercorticosteronemia, enhanced intestinal
      permeability and changes in gut microbiota structure. All of these changes in MS
      rats were prevented by treatment with BBG9-1. Although the gut microbiota profile
      and basal serum corticosterone level did not differ between MS and control rats
      at postnatal day 56, MS rats showed hypersensitivity to restraint stress in terms
      of serum corticosterone level and fecal frequency. However, such hypersensitivity
      was not observed in MS rats treated with BBG9-1. These findings suggest that MS
      initiates the link between gut microbiota alteration and hypersensitivity to
      stress and that the triggering of this process can be prevented by the treatment
      with the probiotic BBG9-1.

PMID- 30120331
TI  - Simple rules for construction of a geometric nest structure by pufferfish.
AB  - A small (~10 cm) male pufferfish (Torquigener albomaculosus) builds a large (~2
      m) sandy nest structure, resembling a mysterious crop circle, to attract females.
      The circle consists of radially arranged deep ditches in the outer ring region,
      and maze-like shallow ditches in the central region. The configuration is
      geometrical. Here, we examined the process of the outer ring construction, and
      extracted the 'rules' followed by the pufferfish. During construction, the
      pufferfish repeatedly excavates ditches from the outside in. Generally,
      excavation starts at lower positions, and occurs in straight lines. The entry
      position, the length, and the direction of each ditch were recorded. A simulation
      program based on these data successfully reproduced the circle pattern,
      suggesting that the complex circle structure can be created by the repetition of
      simple actions by the pufferfish.

PMID- 30120332
TI  - Expression profiling in a mammalian host reveals the strong induction of genes
      encoding LysM domain-containing proteins in Enterococcus faecium.
AB  - Enterococcus faecium is an important health care-associated pathogen that is
      difficult to treat due to the high level of antibiotic resistance of clinical
      isolates. The identification of new potential therapeutic targets or vaccination
      strategies is therefore urgently needed. In this regard, we carried out a
      transcriptomic analysis of the E. faecium vancomycin-resistant strain AUS0004,
      comparing the gene expression of bacteria grown under laboratory conditions and
      bacteria isolated from an infection site. This analysis highlighted more than 360
      genes potentially induced under infection conditions. Owing to their expression
      profiles, four LysM domain-containing proteins were characterized in more detail.
      The EFAU004_01059, 1150 and 494 proteins are highly homologous, whereas
      EFAU004_01209 has a unique domain-architecture and sequence. The analysis of
      corresponding mutants showed that all LysM proteins played relevant roles in the
      infection process of E. faecium in mice. The EFAU004_01209 mutant also displayed
      profound morphological modifications, suggesting it has a role in cell wall
      synthesis or cell division. Furthermore, the adhesion to kidney cells and growth
      of the mutant was affected in human urine. All these phenotypes and the surface
      exposure of EFAU004_01209 identify this protein as an interesting new drug target
      in E. faecium.

PMID- 30120334
TI  - Gravity measurements below 10-9 g with a transportable absolute quantum
      gravimeter.
AB  - Gravimetry is a well-established technique for the determination of sub-surface
      mass distribution needed in several fields of geoscience, and various types of
      gravimeters have been developed over the last 50 years. Among them, quantum
      gravimeters based on atom interferometry have shown top-level performance in
      terms of sensitivity, long-term stability and accuracy. Nevertheless, they have
      remained confined to laboratories due to their complex operation and high
      sensitivity to the external environment. Here we report on a novel,
      transportable, quantum gravimeter that can be operated under real world
      conditions by non-specialists, and measure the absolute gravitational
      acceleration continuously with a long-term stability below 10 nm.s-2 (1 MUGal).
      It features several technological innovations that allow for high-precision
      gravity measurements, while keeping the instrument light and small enough for
      field measurements. The instrument was characterized in detail and its stability
      was evaluated during a month-long measurement campaign.

PMID- 30120333
TI  - Comparison of radiation dermatitis between hypofractionated and conventionally
      fractionated postoperative radiotherapy: objective, longitudinal assessment of
      skin color.
AB  - This study aimed to quantitatively compare radiation dermatitis due to
      hypofractionated (Hypo) and conventionally fractionated (Conv) external-beam
      radiotherapy in patients who underwent postoperative radiotherapy after breast
      conserving surgery. Skin color changes, in terms of L* (brightness, white-black),
      a* (red-green), and b* (yellow-blue) values, due to external-beam radiotherapy
      were examined at alternate fractions using an objective method. Twenty-six
      patients were included in the Hypo group (42.56 Gy/16 fractions) and 46 in the
      Conv group (50 Gy/25 fractions). Radiotherapy decreased the L* value (darker) and
      increased the a* value (redder) gradually. These color alterations progressed
      linearly according to elapsed fractions and were similar between Hypo and Conv
      per fraction. The Hypo group showed significantly milder alterations in L* and a*
      values than the Conv group. The maximal dosage was significantly correlated to
      alterations in L* and a* values. Common Terminology Criteria for Adverse Events
      v4 assessment did not show a statistically significant difference between the
      Hypo (Grade 0:1:2 = 2:24:1) and Conv (1:39:6, p = 0.25) groups. The results of
      our objective analysis revealed that patients undergoing Hypo show milder color
      alteration than those undergoing Conv and that the maximal dosage is a useful
      predicator of color alteration.

PMID- 30120335
TI  - Co3O4/carbon composite nanofibrous membrane enabled high-efficiency
      electromagnetic wave absorption.
AB  - Electromagnetic (EM) wave absorbing materials have been fabricated from diverse
      materials such as conductive polymers, carbon based nanostructures and magnetic
      metal oxides. Nevertheless, it has remained a great challenge to develop
      lightweight and high-efficiency EM wave absorbing materials with a broad
      frequency range. Herein, we report a scalable strategy to create Co3O4/carbon
      composite nanofibrous membrane by electrospinning technique followed by
      stabilization and carbonization processes. An optimal reflection loss (RL) value
      of 36.27 dB is reached at 13.76 GHz for a layer of 2 mm thickness. RL exceeding 
      20 dB can be realized in any interval within the 4.5-14.4 GHz range by selecting
      a proper thickness of the absorbing layer between 1 and 5 mm. The Co3O4/carbon
      composite nanofibrous membrane could be well served as promising and attractive
      candidates for lightweight and enhanced EM wave absorbing materials. This
      presented research provides an innovative and effective approach to design the
      novel EM wave absorbing material in a broad frequency range for practical
      applications.

PMID- 30120336
TI  - Genome-wide Association Analysis of Eye Movement Dysfunction in Schizophrenia.
AB  - Eye movements are considered endophenotypes of schizophrenia. However, the
      genetic factors underlying eye movement are largely unknown. In this study, we
      explored the susceptibility loci for four eye movement scores: the scanpath
      length during the free viewing test (SPL), the horizontal position gain during
      the fast Lissajous paradigm of the smooth pursuit test (HPG), the duration of
      fixations during the far distractor paradigm of the fixation stability test (DF)
      and the integrated eye movement score of those three scores (EMS). We found 16
      SNPs relevant to the HPG that were located in 3 genomic regions (1q21.3, 7p12.1
      and 20q13.12) in the patient group; however, these SNPs were intronic or
      intergenic SNPs. To determine whether these SNPs occur in functional non-coding
      regions (i.e., enhancer or promoter regions), we examined the chromatin status on
      the basis of publicly available epigenomic data from 127 tissues or cell lines.
      This analysis suggested that the SNPs on 1q21.3 and 20q13.12 are in enhancer or
      promoter regions. Moreover, we performed an analysis of expression quantitative
      trait loci (eQTL) in human brain tissues using a public database. Finally, we
      identified significant eQTL effects for all of the SNPs at 1q21.3 and 20q13.12 in
      particular brain regions.

PMID- 30120338
TI  - Human esophageal myofibroblast secretion of bone morphogenetic proteins and
      GREMLIN1 and paracrine regulation of squamous epithelial growth.
AB  - We have previously shown myofibroblasts subjacent to the squamous epithelium in
      the normal human esophagus and an increase in esophagitis. Myofibroblast
      contribution to bone morphogenetic protein (BMP) signaling and to paracrine
      mediated epithelial-mesenchymal interactions in the human esophagus remains
      incompletely defined. We investigated BMP4 and BMP inhibitor GREM1 gene
      expression and protein levels in previously characterized human esophageal
      myofibroblast primary cultures and in a human esophageal myofibroblast cell line.
      We adapted human esophageal myofibroblast conditioned media into a 3D organotypic
      model to investigate the effect of myofibroblast secreted factors on squamous
      epithelial morphology, proliferation, differentiation and BMP signaling. Human
      esophageal myofibroblasts constitutively secrete GREM1 and increase BMP4
      expression and BMP4 secretion in response to epithelial Hedgehog ligand SHH.
      Detection of secreted BMP4 is decreased in the presence of GREM1. Myofibroblast
      conditioned media increases epithelial proliferation and expression of basal
      markers p63 and CK14 leading to an overall increase in epithelial thickness.
      Epithelial BMP signaling increases with myofibroblast conditioned media. These
      findings were partially reversed with GREM1 inhibition. Our results demonstrate
      that myofibroblasts are potential sources of GREM1 and of BMP4 in the human
      esophagus and that human esophageal myofibroblast-epithelial paracrine
      interactions contribute in part to the regulation of epithelial growth.

PMID- 30120337
TI  - Preattentive and Predictive Processing of Visual Motion.
AB  - Interaction with the environment requires fast and reliable sensory processing.
      The visual system is confronted with a continuous flow of high-dimensional input
      (e.g. orientation, color, motion). From a theoretical point of view, it would be
      advantageous if critical information was processed independent of attentional
      load, i.e. preattentively. Here, we hypothesized that visual motion is such a
      critical signal and aimed for a neural signature of its preattentive encoding.
      Furthermore, we were interested in the neural correlates of predictability of
      linear motion trajectories based on the presence or absence of preceding motion.
      We presented a visual oddball paradigm and studied event-related potentials
      (ERPs). Stimuli were linearly moving Gabor patches that disappeared behind an
      occluder. The difference between deviant and standard trials was a trajectory
      change which happened behind the occluder in deviant trials only, inducing a
      prediction error. As hypothesized, we found a visual mismatch negativity
      component over parietal and occipital electrodes. In a further condition, trials
      without preceding motion were presented in which the patch just appeared from
      behind the occluder and, hence, was not predictable. We found larger ERP
      components for unpredictable stimuli. In summary, our results provide evidence
      for a preattentive and predictive processing of linear trajectories of visual
      motion.

PMID- 30120339
TI  - Olea europaea small RNA with functional homology to human miR34a in cross-kingdom
      interaction of anti-tumoral response.
AB  - Functional foods include compounds with nutritional and health properties. The
      human diet could play a stronger role in cancer prevention. Only a few studies
      have described the presence of plant small RNA, in humans who were fed with plant
      foods, which demonstrated the ability of these molecules to modulate consumer's
      genes and evidenced the existence of a plant-animal regulation. Through in silico
      prediction, Olea europaea small RNAs (sRs), which had been previously reported as
      miRNAs, were identified, each with functional homology to hsa-miR34a. According
      to this initial funding, we investigated the ability of oeu-sRs to regulate
      tumorigenesis in human cells. The transfection of these synthetic oeu-sRs reduced
      the protein expression of hsa-miR34a mRNA targets, increased apoptosis and
      decreased proliferation in different tumor cells; by contrast, no effect was
      observed in PBMCs from healthy donors. The introduction of oeu-small RNA in hsa
      miR34a-deficient tumor cells restores its function, whereas cells with normal
      expression of endogenous hsa-miR34a remained unaffected. The natural oeu-small
      RNAs that were extracted from O. europaea drupes induce the same effects as
      synthetic sRs. Careful research on the small RNA sequences executed for mapping
      and annotation in the genome of O. europaea var. Sylvestris and var. Farga led to
      the hypothesis that RNA fragments with functional homology to human miRNAs could
      be generated from the degradation of regions of RNA transcripts. These results
      indicate the possibility of developing novel natural non-toxic drugs that contain
      active plant-derived tumor-suppressing small RNA with functional homology to hsa
      miRNAs and that can support antineoplastic strategies.

PMID- 30120340
TI  - Nuclear connectin novex-3 promotes proliferation of hypoxic foetal
      cardiomyocytes.
AB  - Loss of cardiomyocyte proliferative capacity after birth is a major obstacle for
      therapeutic heart regeneration in adult mammals. We and others have recently
      shown the importance of hypoxic in utero environments for active foetal
      cardiomyocyte proliferation. Here, we report the unexpected expression of novex
      3, the short splice variant of the giant sarcomeric protein connectin (titin), in
      the cardiomyocyte nucleus specifically during the hypoxic foetal stage in mice.
      This nuclear localisation appeared to be regulated by the N-terminal region of
      novex-3, which contains the nuclear localisation signal. Importantly, the nuclear
      expression of novex-3 in hypoxic foetal cardiomyocytes was repressed at the
      postnatal stage following the onset of breathing and the resulting elevation of
      oxygen tension, whereas the sarcomeric expression remained unchanged. Novex-3
      knockdown in foetal cardiomyocytes repressed cell cycle-promoting genes and
      proliferation, whereas novex-3 overexpression enhanced proliferation. Mechanical
      analysis by atomic force microscopy and microneedle-based tensile tests
      demonstrated that novex-3 expression in hypoxic foetal cardiomyocytes contributes
      to the elasticity/compliance of the nucleus at interphase and facilitates
      proliferation, by promoting phosphorylation-induced disassembly of multimer
      structures of nuclear lamins. We propose that novex-3 has a previously
      unrecognised role in promoting cardiomyocyte proliferation specifically at the
      hypoxic foetal stage.

PMID- 30120341
TI  - Predictors of mosaic chromosome Y loss and associations with mortality in the UK
      Biobank.
AB  - Mosaic loss of the Y chromosome (mLOY) is the most commonly reported large
      structural somatic event. Previous studies have indicated age and cigarette
      smoking increase the risk of mLOY, but the relationship of other exposures with
      mLOY and mLOY with disease has not been adequately investigated. We characterized
      mLOY in a large cohort of 223,338 men from the UK Biobank by scanning for
      deviations in genotyping array median log2 intensity ratios (mLRR) of the Y
      chromosome using a standard algorithm. A total of 3,789 (1.7%) men showed
      evidence for mLOY (mLRR < -0.15). In multivariable-adjusted logistic regression
      models, we found that mLOY increases exponentially with age (overall P-value <
      4.9 * 10-324; p-value for the quadratic term = 2.1 * 10-7), and observed a strong
      association with current smoking (P-value = 7.8 * 10-184). We observed less mLOY
      in men of African ancestry (0.4%) compared to men of European ancestry (1.8%, P
      value = 0.003). Although mLOY was not associated with prevalent cancer (P-value =
      0.61), associations were observed for diabetes (P-value = 0.003) and
      cardiovascular disease (P-value = 0.01). Using Cox proportional hazards
      regression models, mLOY was associated with all-cause mortality among men with a
      high proportion of cells affected (mLRR < -0.40; HR = 1.35, 95% CI = 1.08-1.70, P
      value = 0.009). In conclusion, mLOY was associated with several health-related
      factors as well as with all-cause mortality. Further functional studies are
      warranted to understand how and in what way mLOY could influence adult male
      health.

PMID- 30120342
TI  - Near full length genome of a recombinant (E/D) cosavirus strain from a rural area
      in the central region of Brazil.
AB  - In the present article we report the nearly full length genome of a Cosavirus
      strain (BRTO-83) isolated from a child with acute gastroenteritis, and who is an
      inhabitant of a rural area in the central region of Brazil. The sample was
      previously screened and negative for both: common enteric viruses (i.e. rotavirus
      and norovirus), bacteria, endoparasites and helminthes. Evolutionary analysis and
      phylogenetic inferences indicated that the Brazilian BRTO-83 Cosavirus strain was
      a recombinant virus highly related to the E/D recombinant NG385 strain (Genbank
      JN867757), which was isolated in Nigeria from an acute flaccid paralysis patient.
      This is the first report of a recombinant E/D Cosavirus strain detected in
      Brazil, and the second genome described worldwide. Further surveillance and
      molecular studies are required to fully understand the epidemiology, distribution
      and evolution of the Cosavirus.

PMID- 30120343
TI  - Quantifying emergence and self-organisation of Enterobacter cloacae microbial
      communities.
AB  - From microbial communities to cancer cells, many such complex collectives embody
      emergent and self-organising behaviour. Such behaviour drives cells to develop
      composite features such as formation of aggregates or expression of specific
      genes as a result of cell-cell interactions within a cell population. Currently,
      we lack universal mathematical tools for analysing the collective behaviour of
      biological swarms. To address this, we propose a multifractal inspired framework
      to measure the degree of emergence and self-organisation from scarce spatial
      (geometric) data and apply it to investigate the evolution of the spatial
      arrangement of Enterobacter cloacae aggregates. In a plate of semi-solid media,
      Enterobacter cloacae form a spatially extended pattern of high cell density
      aggregates. These aggregates nucleate from the site of inoculation and radiate
      outward to fill the entire plate. Multifractal analysis was used to characterise
      these patterns and calculate dynamics changes in emergence and self-organisation
      within the bacterial population. In particular, experimental results suggest that
      the new aggregates align their location with respect to the old ones leading to a
      decrease in emergence and increase in self-organisation.

PMID- 30120344
TI  - Terrestrial exposure of a fresh Martian meteorite causes rapid changes in
      hydrogen isotopes and water concentrations.
AB  - Determining the hydrogen isotopic compositions and H2O contents of meteorites and
      their components is important for addressing key cosmochemical questions about
      the abundance and source(s) of water in planetary bodies. However, deconvolving
      the effects of terrestrial contamination from the indigenous hydrogen isotopic
      compositions of these extraterrestrial materials is not trivial, because
      chondrites and some achondrites show only small deviations from terrestrial
      values such that even minor contamination can mask the indigenous values. Here we
      assess the effects of terrestrial weathering and contamination on the hydrogen
      isotope ratios and H2O contents of meteoritic minerals through monitored
      terrestrial weathering of Tissint, a recent Martian fall. Our findings reveal the
      rapidity with which this weathering affects nominally anhydrous phases in
      extraterrestrial materials, which illustrates the necessity of sampling the
      interiors of even relatively fresh meteorite falls and underlines the importance
      of sample return missions.

PMID- 30120345
TI  - Evaluation of the diagnostic accuracy of Computer-Aided Detection of tuberculosis
      on Chest radiography among private sector patients in Pakistan.
AB  - The introduction of digital CXR with automated computer-aided interpretation, has
      given impetus to the role of CXR in TB screening, particularly in low resource,
      high-burden settings. The aim of this study was to evaluate the diagnostic
      accuracy of CAD4TB as a screening tool, implemented in the private sector in
      Karachi, Pakistan. This study analyzed retrospective data from CAD4TB and Xpert
      MTB/RIF testing carried out at two private TB treatment and diagnostic centers in
      Karachi. Sensitivity, specificity, potential Xperts saved, were computed and the
      receiver operator characteristic curves were constructed for four different
      models of CAD4TB. A total of 6,845 individuals with presumptive TB were enrolled
      in the study, 15.2% of which had MTB + ve result on Xpert. A high sensitivity
      (range 65.8-97.3%) and NPV (range 93.1-98.4%) were recorded for CAD4TB. The Area
      under the ROC curve (AUC) for CAD4TB was 0.79. CAD4TB with patient demographics
      (age and gender) gave an AUC of 0.83. CAD4TB offered high diagnostic accuracy. In
      low resource settings, CAD4TB, as a triage tool could minimize use of Xpert.
      Using CAD4TB in combination with age and gender data enhanced the performance of
      the software. Variations in demographic information generate different individual
      risk probabilities for the same CAD4TB scores.

PMID- 30120346
TI  - Magnetic order and disorder in nanomagnets probed by superconducting vortices.
AB  - We have studied two nanomagnet systems with strong (Co/Pd multilayers) and weak
      (NdCo alloy films) stray magnetic fields by probing the out-of-plane magnetic
      states with superconducting vortices. The hybrid samples are made of array of
      nanomagnets embedded in superconducting Nb thin films. The vortex motion detects
      relevant magnetic state features, since superconducting vortices are able to
      discriminate between different magnetic stray field strengths and directions. The
      usual matching effect between the superconducting vortex lattice and the periodic
      pinning array can be quenched by means of disorder magnetic potentials with
      strong stray fields at random. Ordered stray fields retrieve the matching effect
      and yield asymmetry and shift in the vortex dissipation signal. Furthermore
      vortices can discriminate the sizes of the nanomagnet magnetic domains, detecting
      magnetic domain sizes as small as 70 nm. In addition, we observe that the vortex
      cores play the crucial role instead of the supercurrents around the vortex.

PMID- 30120347
TI  - Deep soil water storage varies with vegetation type and rainfall amount in the
      Loess Plateau of China.
AB  - Soil-water storage in a deep soil layer (SWSD), defined as the layer where soil
      water is not sensitive to daily evapotranspiration and regular rainfall events,
      functions as a soil reservoir in China's Loess Plateau (LP). We investigated
      spatial variations and factors that influence the SWSD in the 100-500 cm layers
      across the entire plateau. SWSD generally decreased from southeast to northwest
      following precipitation gradient, with a mean value of 587 mm. The spatial
      variation in the SWSD in grassland was the highest, followed by protection
      forests, production forests and cropland. Variation in the >550 mm rainfall zone
      was much lower than that in the <550 mm zone. The significant influencing
      variables explained 22.3-65.2% of the spatial variation in SWSD. The joint effect
      of local and climatic variables accounted for most of the explained spatial
      variation of SWSD for each vegetation type and the <450 mm rainfall zone. Spatial
      variation of SWSD, however, was dominantly controlled by the local variables in
      the 450-550 and the >550 mm rainfall zones. Therefore, regional models of SWSD
      for a specific vegetation need to incorporate climatic, soil and topographic
      variables, while for a rainfall zone, land use should not be ignored.

PMID- 30120349
TI  - APOE*epsilon4 - a risk factor for TDP43 pathology?

PMID- 30120348
TI  - C9orf72-mediated ALS and FTD: multiple pathways to disease.
AB  - The discovery that repeat expansions in the C9orf72 gene are a frequent cause of
      amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) has
      revolutionized our understanding of these diseases. Substantial headway has been
      made in characterizing C9orf72-mediated disease and unravelling its underlying
      aetiopathogenesis. Three main disease mechanisms have been proposed: loss of
      function of the C9orf72 protein and toxic gain of function from C9orf72 repeat
      RNA or from dipeptide repeat proteins produced by repeat-associated non-ATG
      translation. Several downstream processes across a range of cellular functions
      have also been implicated. In this article, we review the pathological and
      mechanistic features of C9orf72-associated FTD and ALS (collectively termed
      C9FTD/ALS), the model systems used to study these conditions, and the probable
      initiators of downstream disease mechanisms. We suggest that a combination of
      upstream mechanisms involving both loss and gain of function and downstream
      cellular pathways involving both cell-autonomous and non-cell-autonomous effects
      contributes to disease progression.

PMID- 30120351
TI  - Author Correction: Cytotoxicity of Aconitum alkaloid and its interaction with
      calf thymus DNA by multi-spectroscopic techniques.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30120350
TI  - Ectopic expression of mutated type 2C protein phosphatase OsABI-LIKE2 decreases
      abscisic acid sensitivity in Arabidopsis and rice.
AB  - Abscisic acid (ABA) is a phytohormone that is necessary for stress adaptation.
      Recent studies have reported that attenuated levels of ABA improved grain yield
      and seedling growth under low temperature in cereals. To improve plant growth
      under low temperature, we attempted to generate ABA-insensitive transgenic rice
      by expressing a clade A type 2C protein phosphatase (OsPP2C), OsABIL2, with or
      without the mutation equivalent to the Arabidopsis abi1-1 mutation. A yeast two
      hybrid assay revealed that the interaction between OsABIL2 and a putative rice
      ABA receptor, OsPYL1, was ABA-dependent, and the interaction was lost with amino
      acid substitution from glycine to aspartic acid at the 183rd amino acid of the
      OsABIL2 protein, corresponding to abi1-1 mutation. The constitutive expression of
      OsABIL2 or OsABIL2G183D in Arabidopsis or rice decreased ABA sensitivity to
      differing degrees. Moreover, the transgenic rice expressing OsABIL2G183D
      exhibited improved seedling growth under low temperature, although the transgenic
      lines showed unfavorable traits, such as viviparous germination and elongated
      internodes. These results indicated that the introduction of abi1-1 type dominant
      mutation was also effective in OsABIL2 at decreasing ABA sensitivity in plants,
      and the attenuation of ABA sensitivity could be an alternative parameter to
      improve rice performance under low temperatures.

PMID- 30120354
TI  - A ribonucleotide trap.

PMID- 30120353
TI  - Carbon fiber doped thermosetting elastomer for flexible sensors: physical
      properties and microfabrication.
AB  - We have developed conductive microstructures using micropatternable and
      conductive hybrid nanocomposite polymer. In this method carbon fibers (CFs) were
      blended into polydimethylsiloxane (PDMS). Electrical conductivities of different
      compositions were investigated with various fiber lengths (50-250 MUm), and
      weight percentages (wt%) (10-60 wt%). Sample composites of 2 cm * 1 cm * 500 MUm
      were fabricated for 4-point probe conductivity measurements. The measured
      percolation thresholds varied with length of the fibers: 50 wt% (307.7 S/m) for
      50 um, 40 wt% (851.1 S/m) for 150 um, and 30 wt% (769.23 S/m) for 250 MUm fibers.
      The conductive composites showed higher elastic modulus when compared to that of
      PDMS.

PMID- 30120352
TI  - Accelerated triacylglycerol production without growth inhibition by
      overexpression of a glycerol-3-phosphate acyltransferase in the unicellular red
      alga Cyanidioschyzon merolae.
AB  - Microalgae accumulate triacylglycerols (TAGs), a promising feedstock for
      biodiesel production, under unfavorable environmental or stress conditions for
      their growth. Our previous analyses revealed that only transcripts of CmGPAT1 and
      CmGPAT2, both encoding glycerol-3-phosphate acyltransferase, were increased among
      fatty acid and TAG synthesis genes under TAG accumulation conditions in the red
      alga Cyanidioschyzon merolae. In this study, to investigate the role of these
      proteins in TAG accumulation in C. merolae, we constructed FLAG-fused CmGPAT1 and
      CmGPAT2 overexpression strains. We found that CmGPAT1 overexpression resulted in
      marked accumulation of TAG even under normal growth conditions, with the maximum
      TAG productivity increased 56.1-fold compared with the control strain, without a
      negative impact on algal growth. The relative fatty acid composition of 18:2 in
      the TAGs and the sn-1/sn-3 positions were significantly increased compared with
      the control strain, suggesting that CmGPAT1 had a substrate preference for 18:2.
      Immunoblot analysis after cell fractionation and immunostaining analysis
      demonstrated that CmGPAT1 localizes in the endoplasmic reticulum (ER). These
      results indicate that the reaction catalyzed by the ER-localized CmGPAT1 is a
      rate-limiting step for TAG synthesis in C. merolae, and would be a potential
      target for improvement of TAG productivity in microalgae.

PMID- 30120355
TI  - TA gets a PG rating.

PMID- 30120356
TI  - Catch and identify your prey.

PMID- 30120357
TI  - Stuck on you.

PMID- 30120358
TI  - An optical sensor to monitor dynamics of extracellular glycine.

PMID- 30120359
TI  - Mimicking cross-alpha amyloids.

PMID- 30120360
TI  - ykkC riboswitches employ an add-on helix to adjust specificity for polyanionic
      ligands.
AB  - The ykkC family of bacterial riboswitches combines several widespread classes
      that have similar secondary structures and consensus motifs but control different
      genes in response to different cellular metabolites. Here we report the crystal
      structures of two distinct ykkC riboswitches specifically bound to their cognate
      ligand ppGpp, a second messenger involved in stress response, or PRPP, a
      precursor in purine biosynthesis. Both RNAs adopt similar structures and contain
      a conserved core previously observed in the guanidine-specific ykkC riboswitch.
      However, ppGpp and PRPP riboswitches uniquely employ an additional helical
      element that joins the ends of the ligand-sensing domains and creates a tunnel
      for direct and Mg2+-mediated binding of ligands. Mutational and footprinting
      experiments highlight the importance of conserved nucleotides forming the tunnel
      and long-distance contacts for ligand binding and genetic response. Our work
      provides new insights into the specificity of riboswitches and gives a unique
      opportunity for future studies of RNA evolution.

PMID- 30120361
TI  - Allosteric mechanisms underlie GPCR signaling to SH3-domain proteins through
      arrestin.
AB  - Signals from 800 G-protein-coupled receptors (GPCRs) to many SH3 domain
      containing proteins (SH3-CPs) regulate important physiological functions. These
      GPCRs may share a common pathway by signaling to SH3-CPs via agonist-dependent
      arrestin recruitment rather than through direct interactions. In the present
      study, 19F-NMR and cellular studies revealed that downstream of GPCR activation
      engagement of the receptor-phospho-tail with arrestin allosterically regulates
      the specific conformational states and functional outcomes of remote beta
      arrestin 1 proline regions (PRs). The observed NMR chemical shifts of arrestin
      PRs were consistent with the intrinsic efficacy and specificity of SH3 domain
      recruitment, which was controlled by defined propagation pathways. Moreover, in
      vitro reconstitution experiments and biophysical results showed that the receptor
      arrestin complex promoted SRC kinase activity through an allosteric mechanism.
      Thus, allosteric regulation of the conformational states of beta-arrestin 1 PRs
      by GPCRs and the allosteric activation of downstream effectors by arrestin are
      two important mechanisms underlying GPCR-to-SH3-CP signaling.

PMID- 30120362
TI  - Thymosin Alpha1-Fc Modulates the Immune System and Down-regulates the Progression
      of Melanoma and Breast Cancer with a Prolonged Half-life.
AB  - Thymosin alpha 1 (Talpha1) is a biological response modifier that has been
      introduced into markets for treating several diseases. Given the short serum half
      life of Talpha1 and the rapid development of Fc fusion proteins, we used genetic
      engineering method to construct the recombinant plasmid to express Talpha1-Fc (Fc
      domain of human IgG4) fusion protein. A single-factor experiment was performed
      with different inducers of varying concentrations for different times to get the
      optimal condition of induced expression. Pure proteins higher than 90.3% were
      obtained by using 5 mM lactose for 4 h with a final production about 160.4 mg/L.
      The in vivo serum half-life of Talpha1-Fc is 25 h, almost 13 times longer than
      Talpha1 in mice models. Also, the long-acting protein has a stronger activity in
      repairing immune injury through increasing number of lymphocytes. Talpha1-Fc
      displayed a more effective antitumor activity in the 4T1 and B16F10 tumor
      xenograft models by upregulating CD86 expression, secreting IFN-gamma and IL-2,
      and increasing the number of tumor-infiltrating CD4+ T and CD8+ T cells. Our
      study on the novel modified Talpha1 with the Fc segment provides valuable
      information for the development of new immunotherapy in cancer.

PMID- 30120364
TI  - A 2'FY-RNA Motif Defines an Aptamer for Ebolavirus Secreted Protein.
AB  - With properties such as stability to long-term storage and amenability to
      repetitive use, nucleic acid aptamers are compatible with many
      sensing/transducing platforms intended for use in remote locations. Sensors with
      these properties are important for quickly identifying ebolavirus outbreaks,
      which frequently start in locations that lack sophisticated equipment. Soluble
      glycoprotein (sGP), an excellent biomarker for ebolaviruses, is produced from the
      same gene as the ebolavirus glycoprotein GP1,2 that decorates the surface of the
      viral particle and is secreted in abundance into the blood stream even during the
      early stages of infection. Here, we report the selection and properties of a
      2'fluoro pyrimidine (2'FY)-modified RNA aptamer, 39SGP1A, that specifically binds
      sGP. We demonstrate by computational and biochemical analysis that the
      recognition motif of 39SGP1A is a novel polypyrimidine-rich sequence. Replacement
      of -F by -OH in the 2' position of the ribose resulted in complete loss of
      affinity for sGP. The protein motif to which the aptamer binds requires an intact
      sGP dimer and binds to an epitope conserved between Ebola virus (EBOV) and Sudan
      virus (SUDV) sGP, the most divergent Ebolavirus species. This identifies 39SGP1A
      as an excellent option for integration on a sensor platform to detect ebolavirus
      infections.

PMID- 30120365
TI  - Post-operative AICS status in completely resected lung cancer patients with pre
      operative AICS abnormalities: predictive significance of disease recurrence.
AB  - The AminoIndexTM Cancer Screening (AICS) system, a plasma-free amino acid (PFAA)
      based multivariate discrimination index, is a blood screening test for lung
      cancer based on the comparison of PFAA concentrations between patients with lung
      cancer and healthy controls. Pre- and post-operative AICS values were compared
      among 72 patients who underwent curative resection for lung cancer. Post
      operative changes in PFAA concentrations were also evaluated. AICS values were
      classified as rank A (0.0-4.9), B (5.0-7.9), or C (8.0-10.0). Rank B-C patients
      were evaluated for outcomes and post-operative changes in their AICS values.
      Twenty-three of the 44 pre-operative rank B-C patients experienced post-operative
      reductions in AICS rank. Only one patient experienced cancer recurrence. Post
      operative changes in PFAA concentrations were associated with the risk of post
      operative cancer recurrence (p = 0.001). Multivariate analysis revealed that the
      absence of a post-operative reduction in AICS rank independently predicted cancer
      recurrence (hazard ratio: 14.28; p = 0.012). The majority of patients had high
      pre-operative AICS values and exhibited a reduction in AICS rank after curative
      resection. However, the absence of a post-operative reduction in AICS rank was
      associated with cancer recurrence, suggesting that AICS rank may be a sensitive
      marker of post-operative recurrence.

PMID- 30120363
TI  - Cardiovascular Interactions between Fibroblast Growth Factor-23 and Angiotensin
      II.
AB  - Both the activation of the renin angiotensin aldosterone system (RAAS) and
      elevations of circulating Fibroblast Growth Factor-23 (FGF-23) have been
      implicated in the pathogenesis of left ventricular hypertrophy (LVH) in chronic
      kidney disease. To investigate potential cross-talk between RAAS and FGF-23, we
      administered angiotensin II (Ang II) to wild-type rodents and the Hyp mouse model
      of excess FGF-23. Ang II administration for four weeks to wild-type rodents
      resulted in significant increases in systolic blood pressure and LVH.
      Unexpectedly, FGF-23 circulating levels were increased by 1.5-1.7 fold in Ang II
      treated animals. In addition, Ang II treatment increased expression of FGF-23
      message levels in bone, the predominant tissue for FGF-23 production, and induced
      expression of FGF-23 and its co-receptor alpha-Klotho in the heart, which
      normally does not express FGF-23 or alpha-Klotho in physiologically relevant
      levels. Hyp mice with elevated FGF-23 exhibited increased blood pressure and LVH
      at baseline. Ang II administration to Hyp mice resulted further increments in
      blood pressure and left ventricular hypertrophy, consistent with additive
      cardiovascular effects. These findings suggest that FGF-23 may participate in
      unexpected systemic and paracrine networks regulating hemodynamic and myocardial
      responses.

PMID- 30120366
TI  - A coalescent-based estimator of genetic drift, and acoustic divergence in the
      Pteronotus parnellii species complex.
AB  - Determining the processes responsible for phenotypic variation is one of the
      central tasks of evolutionary biology. While the importance of acoustic traits
      for foraging and communication in echolocating mammals suggests adaptation, the
      seldom-tested null hypothesis to explain trait divergence is genetic drift. Here
      we derive FST values from multi-locus coalescent isolation-with-migration models,
      and couple them with estimates of quantitative trait divergence, or PST, to test
      drift as the evolutionary process responsible for phenotypic divergence in island
      populations of the Pteronotus parnellii species complex. Compared to traditional
      comparisons of PST to FST, the migration-based estimates of FST are
      unidirectional instead of bidirectional, simultaneously integrate variation among
      loci and individuals, and posterior densities of PST and FST can be compared
      directly. We found the evolution of higher call frequencies is inconsistent with
      genetic drift for the Hispaniolan population, despite many generations of
      isolation from its Puerto Rican counterpart. While the Hispaniolan population
      displays dimorphism in call frequencies, the higher frequency of the females is
      incompatible with sexual selection. Instead, cultural drift toward higher
      frequencies among Hispaniolan females might explain the divergence. By
      integrating Bayesian coalescent and trait analyses, this study demonstrates a
      powerful approach to testing genetic drift as the default evolutionary mechanism
      of trait differentiation between populations.

PMID- 30120367
TI  - A singular value decomposition Bayesian multiple-trait and multiple-environment
      genomic model.
AB  - Today, breeders perform genomic-assisted breeding to improve more than one trait.
      However, frequently there are several traits under study at one time, and the
      implementation of current genomic multiple-trait and multiple-environment models
      is challenging. Consequently, we propose a four-stage analysis for multiple-trait
      data in this paper. In the first stage, we perform singular value decomposition
      (SVD) on the resulting matrix of trait responses; in the second stage, we perform
      multiple trait analysis on transformed responses. In stages three and four, we
      collect and transform the traits back to their original state and obtain the
      parameter estimates and the predictions on these scale variables prior to
      transformation. The results of the proposed method are compared, in terms of
      parameter estimation and prediction accuracy, with the results of the Bayesian
      multiple-trait and multiple-environment model (BMTME) previously described in the
      literature. We found that the proposed method based on SVD produced similar
      results, in terms of parameter estimation and prediction accuracy, to those
      obtained with the BMTME model. Moreover, the proposed multiple-trait method is
      atractive because it can be implemented using current single-trait genomic
      prediction software, which yields a more efficient algorithm in terms of
      computation.

PMID- 30120368
TI  - Controlling Dzyaloshinskii-Moriya Interaction via Chirality Dependent Atomic
      Layer Stacking, Insulator Capping and Electric Field.
AB  - Using first-principles calculations, we demonstrate several approaches to control
      Dzyaloshinskii-Moriya Interaction (DMI) in ultrathin films with perpendicular
      magnetic anisotropy. First, we find that DMI is significantly enhanced when the
      ferromagnetic (FM) layer is sandwiched between nonmagnetic (NM) layers inducing
      additive DMI in NM1/FM/NM2 structures. For instance, when two NM layers are
      chosen to induce DMI of opposite chirality in Co, e.g. NM1 representing Au, Ir,
      Al or Pb, and NM2 being Pt, the resulting DMI in NM1/Co/Pt trilayers is enhanced
      compared to Co/Pt bilayers. Moreover, DMI can be significantly enhanced further
      in case of using FM layer comprising Fe and Co layers. Namely, it is found that
      the DMI in Ir/Fe/Co/Pt structure can be enhanced by 80% compared to that of Co/Pt
      bilayers reaching a very large DMI amplitude of 5.59 meV/atom. Our second
      approach for enhancing DMI is to use oxide capping layer. We show that DMI is
      enhanced by 60% in Oxide/Co/Pt structures compared to Co/Pt bilayers. Moreover,
      we unveiled the DMI mechanism at Oxide/Co interface due to Rashba effect, which
      is different to Fert-Levy DMI at FM/NM interfaces. Finally, we demonstrate that
      DMI amplitude can be modulated using an electric field with an efficiency factor
      comparable to that of the electric field control of perpendicular magnetic
      anisotropy in transition metal/oxide interfaces. These approaches of DMI
      controlling pave the way for skyrmion and domain wall motion-based spintronic
      applications.

PMID- 30120369
TI  - Net-Net Auto Machine Learning (AutoML) Prediction of Complex Ecosystems.
AB  - Biological Ecosystem Networks (BENs) are webs of biological species (nodes)
      establishing trophic relationships (links). Experimental confirmation of all
      possible links is difficult and generates a huge volume of information.
      Consequently, computational prediction becomes an important goal. Artificial
      Neural Networks (ANNs) are Machine Learning (ML) algorithms that may be used to
      predict BENs, using as input Shannon entropy information measures (Shk) of known
      ecosystems to train them. However, it is difficult to select a priori which ANN
      topology will have a higher accuracy. Interestingly, Auto Machine Learning
      (AutoML) methods focus on the automatic selection of the more efficient ML
      algorithms for specific problems. In this work, a preliminary study of a new
      approach to AutoML selection of ANNs is proposed for the prediction of BENs. We
      call it the Net-Net AutoML approach, because it uses for the first time Shk
      values of both networks involving BENs (networks to be predicted) and ANN
      topologies (networks to be tested). Twelve types of classifiers have been tested
      for the Net-Net model including linear, Bayesian, trees-based methods, multilayer
      perceptrons and deep neuronal networks. The best Net-Net AutoML model for 338,050
      outputs of 10 ANN topologies for links of 69 BENs was obtained with a deep fully
      connected neuronal network, characterized by a test accuracy of 0.866 and a test
      AUROC of 0.935. This work paves the way for the application of Net-Net AutoML to
      other systems or ML algorithms.

PMID- 30120370
TI  - Impact of Comorbidities and Smoking on the Outcome in Aneurysmal Subarachnoid
      Hemorrhage.
AB  - The intention of this observational study is to show the significant impact of
      comorbidities and smoking on the outcome in aneurysmal subarachnoid hemorrhage
      (SAH). During this observational study 203 cases of treatment of ruptured
      intracranial aneurysms were analyzed. We examined and classified prospectively
      the 12 month outcome according to the modified Rankin Scale (mRS) considering
      retrospectively a history of smoking and investigated prospectively the
      occurrence of early and delayed cerebral ischemia between 2012 and 2017. Using
      logistic regression methods, we revealed smoking (odds ratio 0.21; p = 0.0031)
      and hypertension (odds ratio 0.18; p = 0.0019) to be predictors for a good
      clinical outcome (mRS 0-2). Age (odds ratio 1.05; p = 0.0092), WFNS Grade (odds
      ratio 6.28; p < 0.0001), early cerebral ischemia (ECI) (odds ratio 10.06; p <
      0.00032) and delayed cerebral ischemia (DCI) (odds ratio 4.03; p = 0.017) were
      detected as predictors for a poor clinical outcome. Significant associations of
      occurrence of death with hypertension (odds ratio 0.12; p < 0.0001), smoking
      (odds ratio 0.31; p = 0.048), WFNS grade (odds ratio 3.23; p < 0.0001) and age
      (odds ratio 1.09; p < 0.0001), but not with ECI (p = 0.29) and DCI (p = 0.62)
      were found. Smoking and hypertension seem to be predictors for a good clinical
      outcome after aneurysmal SAH.

PMID- 30120371
TI  - Polarization-sensitive tunable absorber in visible and near-infrared regimes.
AB  - A broadband tunable absorber is designed and fabricated. The tunable absorber is
      comprised of a dielectric-metal-dielectric multilayer and plasmonic grating. A
      large size of tunable absorber device is fabricated by nano-imprinting method.
      The experimental results show that over 90% absorption can be achieved within
      visible and near-infrared regimes. Moreover, the high absorption can be
      controlled by changing the polarization of incident light. This polarization
      sensitive tunable absorber can have practical applications such as high
      efficiency polarization detectors and transmissive polarizer.

PMID- 30120373
TI  - Optically Graded Ultra Dark Absorber for Visible and Near-infrared Wavelength
      Range.
AB  - Near perfect absorbers find application in many areas including solar cells,
      energy harvesting and antireflection coatings for space applications. Here we
      report the use of optical gradation concept to fabricate a near perfect absorber
      on etched Si wafer. As a proof of concept, 99.4% absorption is achieved in the
      broad range of 300 nm to 2000 nm. Moreover, absorption capacity of optically
      graded surface remains higher than 99% up to beam incident angle of 50 degrees .
      While carbon nanotubes (index ~1.1) are used as top layer, subsequent layers with
      increasing optical index across the thickness are chosen so as to satisfy zero
      reflection condition on multilayered assembly. Inward bending of incident beam
      and total internal reflection of reflected beam caused due to optical index
      gradient contributes to absorb the incident beam more efficiently. In addition,
      multiple scattering of incident beam due to the presence of multiscale feature
      size in graded assembly helps to absorb shorter as well as longer wavelengths of
      incident light. The graded assembly shows contact angle of 160 degrees  with roll
      off angle equal to 5 degrees  implying that the graded absorber is not only super
      black but also superhydrophobic and self-cleaning in nature. The combination of
      properties shown by the super absorber makes it very attractive, especially for
      next generation solar cells to harness energy in the wavelength range of 1000 nm
      to 2000 nm.

PMID- 30120372
TI  - Publisher Correction: Tax havens and global environmental degradation.
AB  - An earlier version of the Supplementary Information was mistakenly uploaded when
      this Perspective was published, and was live until 14 August 2018, when the
      correct version was uploaded.

PMID- 30120374
TI  - Development of an oxidative stress in vitro assay in zebrafish (Danio rerio) cell
      lines.
AB  - The nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator of
      cellular defense against oxidative stress and correlated with classical
      toxicological endpoints. In vitro methods using fish cell lines for the
      assessment of aquatic toxicity are needed for mechanistic studies and as an
      alternative to in vivo. We describe an in vitro assay to study oxidative stress
      using zebrafish cell lines. Transfection efficiency of twelve commercially
      available transfection reagents were tested in the zebrafish cell lines ZFL, ZF4,
      and Pac2. The most efficient reagent for each cell line was selected for further
      experiments. Cells were transiently transfected with an Nrf2-responsive
      luciferase plasmid. The assay was tested using the oxidative stress inducing
      chemicals tertbutylhydroquinone, hydrogen peroxide, and sulforaphane. Of the
      transfected cell lines, ZF4 and ZFL showed higher sensitivity. The latter were
      used to study potential oxidative stress induced by pesticides (diazinon,
      deltamethrin, atrazine, metazachlor, terbutylazine, diuron). Besides known
      inducers, Nrf2 activity was also significantly induced by diazinon, deltametrin,
      diuron, and metazachlor. Activation of Nrf2 by metazachlor is a novel finding.
      The described assay could be a valuable tool for research in toxicology to study
      the stress response of both pure chemicals and environmental water samples.

PMID- 30120376
TI  - miR-22 suppresses DNA ligase III addiction in multiple myeloma.
AB  - Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic
      instability. Here we provide evidence that hyper-activation of DNA ligase III
      (LIG3) is crucial for genomic instability and survival of MM cells. LIG3 mRNA
      expression in MM patients correlates with shorter survival and even increases
      with more advanced stage of disease. Knockdown of LIG3 impairs MM cells viability
      in vitro and in vivo, suggesting that neoplastic plasmacells are dependent on
      LIG3-driven repair. To investigate the mechanisms involved in LIG3 expression, we
      investigated the post-transcriptional regulation. We identified miR-22-3p as
      effective negative regulator of LIG3 in MM. Enforced expression of miR-22 in MM
      cells downregulated LIG3 protein, which in turn increased DNA damage inhibiting
      in vitro and in vivo cell growth. Taken together, our findings demonstrate that
      myeloma cells are addicted to LIG3, which can be effectively inhibited by miR-22,
      promoting a novel axis of genome stability regulation.

PMID- 30120377
TI  - Transition metal doped Sb@SnO2 nanoparticles for photochemical and
      electrochemical oxidation of cysteine.
AB  - Transition metal-doped SnO2 nanoparticles (TM-SnO2) were synthesized by applying
      a thermos-synthesis method, which first involved doping SnO2 with Sb and then
      with transition metals (TM = Cr, Mn, Fe, or Co) of various concentrations to
      enhance a catalytic effect of SnO2. The doped particles were then analyzed by
      using various surface analysis techniques such as transmission electron
      microscopy (TEM), X-ray diffraction (XRD), scanning transmission X-ray microscopy
      (STXM), and high-resolution photoemission spectroscopy (HRPES). We evaluated the
      catalytic effects of these doped particles on the oxidation of L-cysteine (Cys)
      in aqueous solution by taking electrochemical measurements and on the
      photocatalytic oxidation of Cys by using HRPES under UV illumination. Through the
      spectral analysis, we found that the Cr- and Mn-doped SnO2 nanoparticles exhibit
      enhanced catalytic activities, which according to the various surface analyses
      were due to the effects of the sizes of the particles and electronegativity
      differences between the dopant metal and SnO2.

PMID- 30120375
TI  - Comparison of microbiomes of cold-water corals Primnoa pacifica and Primnoa
      resedaeformis, with possible link between microbiome composition and host
      genotype.
AB  - Cold-water corals provide critical habitats for a multitude of marine species,
      but are understudied relative to tropical corals. Primnoa pacifica is a cold
      water coral prevalent throughout Alaskan waters, while another species in the
      genus, Primnoa resedaeformis, is widely distributed in the Atlantic Ocean. This
      study examined the V4-V5 region of the 16S rRNA gene after amplifying and
      pyrosequencing bacterial DNA from samples of these species. Key differences
      between the two species' microbiomes included a robust presence of bacteria
      belonging to the Chlamydiales order in most of the P. pacifica samples, whereas
      no more than 2% of any microbial community from P. resedaeformis comprised these
      bacteria. Microbiomes of P. resedaeformis exhibited higher diversity than those
      of P. pacifica, and the two species largely clustered separately in a principal
      coordinate analysis. Comparison of P. resedaeformis microbiomes from samples
      collected in two submarine canyons revealed a significant difference between
      locations. This finding mirrored significant genetic differences among the P.
      resedaeformis from the two canyons based upon population genetic analysis of
      microsatellite loci. This study presents the first report of microbiomes
      associated with these two coral species.

PMID- 30120378
TI  - Zero-shot fMRI decoding with three-dimensional registration based on diffusion
      tensor imaging.
AB  - Functional magnetic resonance imaging (fMRI) acquisitions include a great deal of
      individual variability. This individuality often generates obstacles to the
      efficient use of databanks from multiple subjects. Although recent studies have
      suggested that inter-regional connectivity reflects individuality, conventional
      three-dimensional (3D) registration methods that calibrate inter-subject
      variability are based on anatomical information about the gray matter shape
      (e.g., T1-weighted). Here, we present a new registration method focusing more on
      the white matter structure, which is directly related to the connectivity in the
      brain, and apply it to subject-transfer brain decoding. Our registration method
      based on diffusion tensor imaging (DTI) transferred functional maps of each
      individual to a common anatomical space, where a decoding analysis of multi-voxel
      patterns was performed. The decoder trained on functional maps from other
      individuals in the common space showed a transfer decoding accuracy comparable to
      that of an individual decoder trained on single-subject functional maps. The DTI
      based registration allowed more precise transformation of gray matter boundaries
      than a well-established T1-based method. These results suggest that the DTI-based
      registration is a promising tool for standardization of the brain functions, and
      moreover, will allow us to perform 'zero-shot' learning of decoders which is
      profitable in brain machine interface scenes.

PMID- 30120379
TI  - Barn swallows long-distance migration occurs between significantly temperature
      correlated areas.
AB  - Organisms are routinely confronted with crucial decisions on the best time and
      place to perform fundamental activities. However, unpredictable spatio-temporal
      variation in ecological factors makes life-history optimization difficult
      particularly for long-distance migrants, which are putatively blind of conditions
      thousands of kilometers and weeks ahead along their journey. Here we challenge,
      on a hierarchy of geographical scales, the common wisdom that migratory birds
      have no clue to ecological conditions at destination. Using ringing data of the
      inter-continental migrating barn swallow (Hirundo rustica), we show that
      temperatures at breeding sites and at times of arrival from migration are more
      correlated with those at actual wintering sites and at times of departure than
      with those at other sites and at periods before/after departure. Hence,
      individual swallows have clues to adjust timing of spring migration based on
      expected conditions at destination, and they apparently choose wintering sites to
      increase availability of such information.

PMID- 30120380
TI  - Metabolism and mitochondria in polycystic kidney disease research and therapy.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common,
      potentially lethal, monogenic diseases and is caused predominantly by mutations
      in polycystic kidney disease 1 (PKD1) and PKD2, which encode polycystin 1 (PC1)
      and PC2, respectively. Over the decades-long course of the disease, patients
      develop large fluid-filled renal cysts that impair kidney function, leading to
      end-stage renal disease in ~50% of patients. Despite the identification of
      numerous dysregulated pathways in ADPKD, the molecular mechanisms underlying the
      renal dysfunction from mutations in PKD genes and the physiological functions of
      the polycystin proteins are still unclear. Alterations in cell metabolism have
      emerged in the past decade as a hallmark of ADPKD. ADPKD cells shift their mode
      of energy production from oxidative phosphorylation to alternative pathways, such
      as glycolysis. In addition, the polycystins seem to play regulatory roles in
      modulating mechanisms and machinery related to energy production and utilization,
      including AMPK, PPARalpha, PGC1alpha, calcium signalling at mitochondria
      associated membranes, mTORC1, cAMP and CFTR-mediated ion transport as well as the
      expression of crucial components of the mitochondrial energy production
      apparatus. In this Review, we explore these metabolic changes and discuss in
      detail the relationship between energy metabolism and ADPKD pathogenesis and
      identify potential therapeutic targets.

PMID- 30120381
TI  - UBXD1 is a mitochondrial recruitment factor for p97/VCP and promotes mitophagy.
AB  - Clearance of damaged mitochondria through mitophagy is critical for maintaining
      mitochondrial fidelity and the prevention of neurodegeneration. Here, we report
      on the UBX domain-containing, p97/VCP cofactor UBXD1/UBXN6/UBXDC2 and its role in
      mitophagy. Recognizing depolarized mitochondria via its C-terminal UBX domain,
      UBXD1 translocates to mitochondria in a Parkin-dependent manner. During Parkin
      independent mitophagy, UBXD1 shows no mitochondrial translocation. Once
      translocated, UBXD1 recruits p97 to mitochondria via a bipartite binding motif
      consisting of its N-terminal VIM and PUB domains. Recruitment of p97 by UBXD1
      only depends on the presence of UBXD1 on mitochondria without the need for
      further mitochondrial signals. Following translocation of UBXD1 to CCCP
      depolarized mitochondria and p97 recruitment, formation of LC3-positive
      autolysosomes is strongly enhanced and autophagic degradation of mitochondria is
      significantly accelerated. Diminished levels of UBXD1 negatively impact
      mitophagic flux in Parkin-expressing cells after CCCP treatment. Thus, our data
      supports a model, whereby the p97 cofactor UBXD1 promotes Parkin-dependent
      mitophagy by specifically recognizing damaged mitochondria undergoing autophagic
      clearance.

PMID- 30120383
TI  - Limited success with clostridium collagenase histolyticum following FDA approval
      for the treatment of Peyronie's disease.
AB  - Collagenase clostridium histolyticum (CCH) was approved for the treatment of
      Peyronie's disease (PD) in December of 2013. Recently, further research has
      supported its use. The aim of this study was to objectively evaluate the effects
      of CCH on penile curvature associated with Peyronie's disease at our high volume
      institution. Since the approval of CCH for PD, 45 men have undergone between 1
      and 4 treatment cycles (mean 3.13, standard deviation (SD) = 0.87) at our
      institution. Primary as well as secondary curvature, if any, was measured before
      beginning therapy and after each cycle of therapy. The degree of curvature was
      compared. We also questioned these men about their subjective experience with
      CCH. The mean age of this cohort was 55.7 years (range 35-70). The mean primary
      curvature was 53.6 degrees  (SD = 16.5). Post-treatment mean primary curvature
      was 48.2 degrees  (SD = 19.5), p = 0.10. Secondary curvature was reduced from
      24.1 degrees  (SD = 11.3) to 20.4 degrees  (SD = 11.5) before and after treatment
      with CCH, respectively, p = 0.27. There were two tunical ruptures in this series
      after which both ceased therapy with CCH. Additionally, 37/45 patients in this
      series expressed some degree of dissatisfaction in their post-therapy visits with
      most of these men stating that they did not notice a change in their curvature.
      CCH remains an option for the treatment of PD. Predictors of success, however,
      are lacking. Our experience showed a less-robust response to CCH than previous
      studies and underscores the need for effective and clear patient counseling prior
      to the initiation of therapy with CCH for PD in the post-FDA-approval setting.

PMID- 30120382
TI  - Density functional theory study of the role of benzylic hydrogen atoms in the
      antioxidant properties of lignans.
AB  - Antioxidants are a diverse group of chemicals with proven health benefits and
      thus potential preventive medicine and therapeutic applications. While most of
      these compounds are natural products, determining their mechanism of radical
      scavenging and common motifs that contribute to antioxidant activity would allow
      the rational design of novel antioxidants. Here the origins of the antioxidant
      properties of ten natural products of the lignan family were studied in silico by
      calculating their thermochemical properties by using ROB3LYP/6
      311++G(2df,2p)//B3LYP/6-311G(d,p) model chemistry. Three conditions were
      modelled: gas phase, ethanol and water solvents. The results allowed assigning
      the antioxidant activity to specific moieties and structural features of these
      compounds. It was found that the benzylic hydrogen atoms are the most likely to
      be abstracted to form radicals and hence define antioxidant properties in most of
      the studied compounds. The results also suggested that the most likely mechanism
      of HOO* radical scavenging differs by the key moiety: it is hydrogen atom
      transfer in case the benzylic C-H bonds, however it is proton coupled electron
      transfer in case of the compounds where O-H bonds are responsible for radical
      scavenging.

PMID- 30120384
TI  - Effects of low-intensity shock wave therapy (LiST) on the erectile tissue of
      naturally aged rats.
AB  - Low-intensity shock wave therapy (LiST) improves erectile function in patients
      with erectile dysfunction (ED), probably by promoting angiogenesis as suggested
      by studies on animals with comorbidities as disease associated ED models. We aim
      to investigate the effects of LiST on erectile tissue of healthy, naturally aged
      rats. Twelve naturally aged male rats were randomized into two groups: control
      group (n = 6) and LiST-treatment group (n = 6). Young rats (8 weeks) (n = 6) was
      also used as control. Each rat in treatment group received 300 shock waves with
      an energy flux density of 0.09 mJ/mm2 at 2 Hz. Sessions were repeated three
      times/week for 2 weeks, followed by a 2-week washout period. Real-time RT-PCR for
      the expressions of vascular endothelial growth factor (VEGF), endothelial nitric
      oxide synthase (eNOS), nerve growth factor (NGF), neuronal NOS (nNOS), as well as
      alpha1 and alpha2-adrenergic receptors (alpha1AR, alpha2AR) was performed,
      followed by immunohistochemical analysis (IHC) to evaluate protein expression.
      The expressions of VEGF, eNOS, and alpha2AR/alpha1AR ratio were increased after
      LiST (p = 0.039, p = 0.008, and p = 0.006 respectively). The increase of VEGF,
      eNOS, and alpha2AR was confirmed in IHC (p = 0.013, p = 0.092, and p = 0.096,
      respectively). The increase of VEGF and eNOS seem to play key role in the
      mechanism of action of LiST, apparently by inducing angiogenesis. The altered
      expression of alpha1/alpha2-adrenergic receptors could indicate a decrease in
      sympathetic activity. LiST showed to partially reverse changes associated with
      aging in erectile tissue of rats, which supports future research for ED
      prevention.

PMID- 30120385
TI  - Maternal haemoglobin concentrations before and during pregnancy as determinants
      of the concentrations of children at 3-5 years of age: A large follow-up study.
AB  - OBJECTIVE: To examine the association between haemoglobin (Hb) concentrations in
      mothers before and during pregnancy and those in children at 3-5 years of age.
      METHODS: The study included 78,923 women who conceived during 1993-1996 and
      delivered a singleton live infant. Maternal Hb concentrations were measured at
      pre-pregnancy health check-up and first prenatal visit, and during the second and
      third trimester. Hb concentrations of children born to these women were measured
      at 3-5 years of age. Associations between Hb levels in mothers and children were
      examined. Unconditional logistic regression was used to explore the association
      between maternal Hb levels and risk for anaemia in children. RESULTS: Maternal Hb
      levels before and during pregnancy were positively associated with children's Hb
      levels. Using maternal Hb >= 130 g/L as the referent, the risk for anaemia in
      children at 3-5 years of age was higher when maternal second trimester Hb
      concentrations were 70-99 g/L (odds ratio [OR] = 1.76, 95% confidence interval
      [CI] = 1.56-1.99), 100-109 g/L (OR = 1.45, 95% CI = 1.29-1.64), and 110-119 g/L
      (OR = 1.18, 95% CI = 1.04-1.33). Children were 1.52 and 1.23-times more likely to
      suffer from anaemia when maternal third trimester Hb concentrations were 70-99
      and 100-109 g/L, respectively. A pre-pregnancy Hb concentration of 80-109 g/L and
      first prenatal visit Hb concentrations of 80-109 and 100-119 g/L were also
      associated with increased risks for childhood anaemia. CONCLUSION: Low maternal
      Hb concentrations before or during pregnancy increase the risk for anaemia in
      children at 3-5 years of age.

PMID- 30120387
TI  - Author Correction: A comparative genomics and reductive dehalogenase gene
      transcription study of two chloroethene-respiring bacteria, Dehalococcoides
      mccartyi strains MB and 11a.
AB  - A correction to this article has been published and is linked from the HTML and
      PDF versions of this paper. The error has been fixed in the paper.

PMID- 30120386
TI  - The utility of delta neutrophil index in differentiation of pulmonary
      tuberculosis from community acquired pneumonia.
AB  - No data exist on the usefulness of the delta neutrophil index (DNI) to
      discriminate pulmonary tuberculosis (PTB) from community-acquired pneumonia
      (CAP). We performed a retrospective cohort study involving patients with PTB (n =
      62) and CAP (n = 215), and compared their initial DNI levels. The median DNI
      values were 0% (interquartile ranges [IQR] 0-0.2%) and 1.6% (IQR 0.7-2.9%) in PTB
      and CAP, respectively, which was significantly lower in PTB patients (P < 0.001).
      Sixty-nine percent of patients with PTB had DNI value of 0%; however, only 15% of
      patients with CAP had 0% DNI. The discriminatory power of the DNI for diagnosing
      PTB was high with 89% sensitivity and 67% specificity at a DNI cut-off <= 1.0%
      (area under the curve, 0.852). The diagnostic sensitivity and negative predictive
      value (NPV) for PTB were 89% (55/62) and 95% (145/152) at the DNI cut-off <=
      1.0%, respectively, and in multivariate analyses after adjusting for other
      factors (smoking, no fever, upper lobe involvement), DNI <= 1.0% remained
      significant (odds ratio, 15.265; P < 0.001). We demonstrated that the DNI was
      lower in PTB compared with CAP, and an initially elevated DNI (>1.0%) may be
      useful to rule out the possibility of PTB due to its high NPV.

PMID- 30120389
TI  - Self-healing effects in a semi-ordered liquid for stable electronic conversion of
      high-energy radiation.
AB  - Radiation damage in solid-state semiconductors has, until now, placed strict
      limitations on the acceptable decay energies of radioisotopes in radiovoltaic
      cells. Relegation to low-energy beta-emitting isotopes has minimized the power
      output from these devices and limited the technology's ability to deliver greater
      energy densities and longer lifetimes than conventional batteries. We demonstrate
      the self-healing abilities of a liquid-phase semiconducting alloy which can
      withstand high-energy alpha radiation. Neutron diffraction of liquid selenium
      sulfur shows the liquid phase repairing damage sustained in the irradiation of
      the solid phase. This self-healing behavior results in long-lived power output in
      a liquid selenium-sulfur alphavoltaic cell. To the best of our knowledge, this
      marks the only successful demonstration of resistance to high-energy radiation
      (>500 keV) in a semiconducting material. This new robustness can potentially
      allow increases to the available energy density in radiovoltaic cells near 1000
      times the current state of the art.

PMID- 30120388
TI  - Impact of the hypoxic phenotype on the uptake and efflux of nanoparticles by
      human breast cancer cells.
AB  - Breast cancer cells adapt to the hypoxic tumoral environment by undergoing
      changes in metabolism, cell signalling, endo-lysosomal receptor uptake and
      recycling. The resulting hypoxic cell phenotype has the potential to undermine
      the therapeutic efficacy of nanomedicines designed for endocytic uptake and
      specific intracellular trafficking. The aim of this study was to examine the
      impact of hypoxia and simulated reperfusion on the in vitro uptake and release of
      nanomedicines by human breast cancer cells. Cells were exposed to a hypoxic
      preconditioning treatment in 1% oxygen for 6 and 24 hours to induce temporal
      changes in the hypoxic circuit (e.g. HIF-1alpha expression). The preconditioned
      cells were then dosed with nanoparticles for 45 or 180 minutes emulating
      nanomedicine access following tumor reperfusion. Hypoxic preconditioning
      significantly increased nanoparticle retention by up to 10% when compared to
      normoxic cultures, with the greatest relative difference between normoxic and
      hypoxic cultures occurring with a 45 minute dosing interval. Exocytosis studies
      indicated that the preconditioned cells had a significantly increased
      nanoparticle efflux (up to 9%) when compared to normoxic cells. Overall, we were
      able to show that hypoxic preconditioning regulates both the endocytosis and
      exocytosis of nanomedicines in human breast cancer cells.

PMID- 30120391
TI  - Metformin in pregnancy - safe or sorry?

PMID- 30120390
TI  - Physiologically based pharmacokinetic modelling of atomoxetine with regard to
      CYP2D6 genotypes.
AB  - Atomoxetine is a norepinephrine reuptake inhibitor indicated in the treatment of
      attention-deficit/hyperactivity disorder. It is primarily metabolized by CYP2D6
      to its equipotent metabolite, 4-hydroxyatomoxetine, which promptly undergoes
      further glucuronidation to an inactive 4-HAT-O-glucuronide. Clinical trials have
      shown that decreased CYP2D6 activity leads to substantially elevated atomoxetine
      exposure and increase in adverse reactions. The aim of this study was to to
      develop a pharmacologically based pharmacokinetic (PBPK) model of atomoxetine in
      different CYP2D6 genotypes. A single 20 mg dose of atomoxetine was given to 19
      healthy Korean individuals with CYP2D6*wt/*wt (*wt = *1 or *2) or CYP2D6*10/*10
      genotype. Based on the results of this pharmacokinetic study, a PBPK model for
      CYP2D6*wt/*wt individuals was developed. This model was scaled to those with
      CYP2D6*10/*10 genotype, as well as CYP2D6 poor metabolisers. We validated this
      model by comparing the predicted pharmacokinetic parameters with diverse results
      from the literature. The presented PBPK model describes the pharmacokinetics
      after single and repeated oral atomoxetine doses with regard to CYP2D6 genotype
      and phenotype. This model could be utilized for identification of appropriate
      dosages of atomoxetine in patients with reduced CYP2D6 activity to minimize the
      adverse events, and to enable personalised medicine.

PMID- 30120393
TI  - Evaluation of LL-37 antimicrobial peptide derivatives alone and in combination
      with vancomycin against S. aureus.
AB  - Treatment of Staphylococcus aureus infections continues to be a challenge due to
      antimicrobial resistance. Endogenous antimicrobial peptides may offer a new
      option for treating S. aureus infections but several factors limit their clinical
      utility. Herein, we studied the activity of the antimicrobial peptide LL-37 and
      two truncated derivatives, LL-13 and LL-17 alone and in combination with
      vancomycin against a range of drug-resistant S. aureus strains including
      methicillin resistant S. aureus (MRSA) and vancomycin resistant S. aureus (VRSA)
      strains in vitro. When used with vancomycin, LL-13 and LL-17 displayed synergy
      against VRSA and showed the ability to restore sensitivity to vancomycin after
      pretreatment. In addition, LL-13 and LL-17 showed a strong ability to inhibit S.
      aureus biofilm production. LL-37 derivatives may be useful in treating infections
      that are resistant to vancomycin or in scenarios where biofilm formation is a
      concern.

PMID- 30120394
TI  - Novel desferrioxamine derivatives synthesized using the secondary metabolism
      specific nitrous acid biosynthetic pathway in Streptomyces davawensis.
AB  - Recently, a novel nitrous acid biosynthetic pathway composed of two enzymes was
      discovered to be involved in the biosynthesis of cremeomycin for the formation of
      its diazo group. In this pathway, CreE oxidizes L-aspartic acid to nitrosuccinic
      acid and CreD liberates nitrous acid from nitrosuccinic acid. Bioinformatic
      analysis showed that various actinobacteria have putative secondary metabolite
      biosynthesis gene clusters containing creE and creD homologs, suggesting that
      this pathway is widely used for the biosynthesis of various natural products.
      Here, we focused on creE and creD homologs (BN159_4422 and BN159_4421) in
      Streptomyces davawensis. In vitro analysis of recombinant BN159_4422 and
      BN159_4421 proteins showed that these enzymes synthesized nitrous acid from L
      aspartic acid. Secondary metabolites produced by this gene cluster were
      investigated by comparing the metabolic profiles of the wild-type and
      DeltaBN159_4422 strains. When these strains were co-cultured with Tsukamurella
      pulmonis TP-B0596, three compounds were specifically produced by the wild-type
      strain. These compounds were identified as novel desferrioxamine derivatives
      containing either of two unique five-membered heterocyclic ring structures and
      shown to have iron-binding properties. A putative desferrioxamine biosynthetic
      gene cluster was found in the S. davawensis genome, and inactivation of a desD
      homolog (BN159_5485) also abolished the production of these compounds. We propose
      that these compounds should be synthesized by the modification of desferrioxamine
      B and a shorter chain analog using nitrous acid produced by the CreE and CreD
      homologs. This study provides an important insight into the diverse usage of the
      secondary metabolism-specific nitrous acid biosynthetic pathway in actinomycetes.

PMID- 30120395
TI  - Early detection of microvascular dysfunction in hypertension: the holy grail of
      cardiovascular prevention and risk assessment?

PMID- 30120392
TI  - Genomic Analysis of the Insect-Killing Fungus Beauveria bassiana JEF-007 as a
      Biopesticide.
AB  - Insect-killing fungi have high potential in pest management. A deeper insight
      into the fungal genes at the whole genome level is necessary to understand the
      inter-species or intra-species genetic diversity of fungal genes, and to select
      excellent isolates. In this work, we conducted a whole genome sequencing of
      Beauveria bassiana (Bb) JEF-007 and characterized pathogenesis-related features
      and compared with other isolates including Bb ARSEF2860. A large number of Bb JEF
      007 genes showed high identity with Bb ARSEF2860, but some genes showed moderate
      or low identity. The two Bb isolates showed a significant difference in
      vegetative growth, antibiotic-susceptibility, and virulence against Tenebrio
      molitor larvae. When highly identical genes between the two Bb isolates were
      subjected to real-time PCR, their transcription levels were different,
      particularly in heat shock protein 30 (hsp30) gene which is related to conidial
      thermotolerance. In several B. bassiana isolates, chitinases and trypsin-like
      protease genes involved in pathogenesis were highly conserved, but other genes
      showed noticeable sequence variation within the same species. Given the
      transcriptional and genetic diversity in B. bassiana, a selection of virulent
      isolates with industrial advantages is a pre-requisite, and this genetic approach
      could support the development of excellent biopesticides with intellectual
      property protection.

PMID- 30120396
TI  - Intracerebroventricular administration of bone marrow-derived cells attenuates
      angiotensin II-initiated neurogenic hypertension in rats.
AB  - Bone marrow-derived cells exert anti-inflammatory actions and can migrate into
      the brain. However, their role in the development of neurogenic hypertension
      remains unclear. A hyperactive renin-angiotensin system and inflammation in the
      brain are mechanisms that contribute to angiotensin II-initiated neurogenic
      hypertension. We hypothesized that bone marrow-derived cells in the brain
      attenuate the overactive brain renin-angiotensin system and inflammation, thereby
      reducing neurogenic hypertension. We cultured plastic-adherent bone marrow
      derived cells for 3 weeks. Seven days after initiation of vehicle or angiotensin
      II infusions, the rats underwent intracerebroventricular administration of either
      serum-free medium or autologous bone marrow-derived cells (106 cells). After 23
      days of infusion, the mean arterial pressure was recorded, and the sympathetic
      tone was evaluated. Rats infused with angiotensin II demonstrated significant
      increases in the resting mean arterial pressure and the peak depressor response
      to ganglionic blockade (vehicle vs. angiotensin II infusion, 119 +/- 4 vs. 178 +/
      6 mmHg and -34 +/- 6 vs. -74 +/- 5 mmHg, respectively).
      Intracerebroventricularly administered bone marrow-derived cells attenuated the
      angiotensin II-mediated increases in the resting mean arterial pressure and peak
      depressor response (142 +/- 11 and -52 +/- 4 mmHg, respectively). The cells also
      reduced the angiotensin II-induced increases in angiotensin II type 1 receptor
      and transforming growth factor-beta expression in the brain. In conclusion, bone
      marrow-derived cells in the brain may have a protective role against the
      development of angiotensin II-induced neurogenic hypertension by modulating
      angiotensin II type 1 receptor expression and inflammatory processes.

PMID- 30120397
TI  - Hypertension-induced cognitive impairment: insights from prolonged angiotensin II
      infusion in mice.
AB  - The causal relation between hypertension and cerebral small vessel disease (cSVD)
      remains elusive, and appropriate animal models are scarce. We aimed to assess the
      relevance of prolonged angiotensin II-induced hypertension in mice for the study
      of cSVD.Adult male C57BL/6 mice were continuously infused for 3 months with
      Angiotensin II (Ang II; 2 ug/kg/min, sc) or saline (control) via osmotic
      minipumps. Blood pressure, neurological function, locomotor activity, and working
      memory (Y-maze alternation task) were assessed throughout the study. Short-term
      memory performance (object location task) was measured after 3 months of
      infusion. Blood-brain barrier (BBB) function was assessed by the presence of IgG
      leakage and quantified in each brain area of interest. Microglial activation and
      myelin loss were studied in the areas of leakage.Systolic blood pressure
      increased and remained elevated over the 3 months of Ang II infusion, while
      neurological scores and locomotor activity did not change. Working memory
      performance was also not changed, yet short-term memory performance was impaired
      in Ang II-treated mice compared to controls. While BBB leakages were present in
      both groups, mainly in the neocortex, hippocampus, and cerebral nuclei, Ang II
      treated mice showed greater leakage than control mice, along with greater
      microglial density and soma size. Myelin loss was observed for the largest
      leaks.Prolonged Ang II-induced hypertension is associated with large BBB leaks,
      microglial activation, myelin loss, and memory dysfunction in the absence of
      stroke.

PMID- 30120398
TI  - Alberta wildfire 2016: Apt contribution from anomalous planetary wave dynamics.
AB  - In May-June 2016 the Canadian Province of Alberta suffered one of the most
      devastating wildfires in its history. Here we show that in mid-April to early May
      2016 the large-scale circulation in the mid- and high troposphere of the middle
      and sub-polar latitudes of the northern hemisphere featured a persistent high
      amplitude planetary wave structure dominated by the non-dimensional zonal wave
      number 4. The strongest anticyclonic wing of this structure was located over
      western Canada. In combination with a very strong El Nino event in winter
      2015/2016 this favored highly anomalous, tinder-dry and high-temperature
      conditions at the surface in that area, entailing an increased fire hazard there.
      This critically contributed to the ignition of the Alberta Wildfire in May 2016,
      appearing to be the costliest disaster in Canadian history thus far.

PMID- 30120400
TI  - The effect of statin exposure on choroidal neovascularization in nonexudative age
      related macular degeneration patients.

PMID- 30120399
TI  - The threshold for the McGurk effect in audio-visual noise decreases with
      development.
AB  - Across development, vision increasingly influences audio-visual perception. This
      is evidenced in illusions such as the McGurk effect, in which a seen mouth
      movement changes the perceived sound. The current paper assessed the effects of
      manipulating the clarity of the heard and seen signal upon the McGurk effect in
      children aged 3-6 (n = 29), 7-9 (n = 32) and 10-12 (n = 29) years, and adults
      aged 20-35 years (n = 32). Auditory noise increased, and visual blur decreased,
      the likelihood of vision changing auditory perception. Based upon a proposed
      developmental shift from auditory to visual dominance we predicted that younger
      children would be less susceptible to McGurk responses, and that adults would
      continue to be influenced by vision in higher levels of visual noise and with
      less auditory noise. Susceptibility to the McGurk effect was higher in adults
      compared with 3-6-year-olds and 7-9-year-olds but not 10-12-year-olds. Younger
      children required more auditory noise, and less visual noise, than adults to
      induce McGurk responses (i.e. adults and older children were more easily
      influenced by vision). Reduced susceptibility in childhood supports the theory
      that sensory dominance shifts across development and reaches adult-like levels by
      10 years of age.

PMID- 30120401
TI  - Role of retinal image-based counseling in the treatment of peripheral retinal
      lesions.

PMID- 30120402
TI  - Physicians' experiences, attitudes and challenges in a Pediatric Telemedicine
      Service.
AB  - BACKGROUND: Telemedicine in general, and telephone triage, in particular, is
      considered a high-stress clinical activity and involves decision making under
      conditions of uncertainty and urgency. AIM: We wanted to explore the experiences,
      attitudes, and challenges of the physicians in a Pediatric Telemedicine Service
      operated in Israel, and to explore whether the doctors are using non-medical
      factors (not related to the medical problem), when making the clinical decisions
      in this setting. METHODS: We used a qualitative methodology in order to obtain
      rich data that would reflect the participants' subjective experiences. Fifteen
      physicians who worked during the last 5 years in the "Pediatrician Online of
      Clalit" service were interviewed. Data were analyzed thematically. FINDINGS:
      Seven main themes concerning the physicians' challenges during their work at this
      service were revealed, including difficulties diagnosing from a distance,
      treating unfamiliar patients, working alone, urgency and load of calls,
      technological obstacles, and a "moral conflict" between the desire to meet
      parents' expectations and maintain standards of care. The physicians stated that
      non-medical factors also affect their decisions. CONCLUSIONS: In telemedicine
      setting, physicians face various difficulties and challenges, requiring special
      expertise, qualities and skills. Special measures are needed to obtain proper
      diagnosis and decisions.

PMID- 30120403
TI  - Serum, plasma and erythrocyte membrane lipidomes in infants fed formula
      supplemented with bovine milk fat globule membranes.
AB  - BACKGROUND: Supplementation of formula with bovine milk fat globule membranes has
      been shown to narrow the gap in immunological and cognitive development between
      breast-fed and formula-fed infants. METHOD: In a double-blinded randomized
      controlled trial 160 formula-fed infants received an experimental formula (EF),
      supplemented with bovine milk fat globule membranes, or standard formula until 6
      months of age. A breast-fed reference group was recruited. Lipidomic analyses
      were performed on plasma and erythrocyte membranes at 6 months and on serum at 4
      and 12 months of age. RESULTS: At 6 months of age, we observed a significant
      separation in the plasma lipidome between the two formula groups, mostly due to
      differences in concentrations of sphingomyelins (SM), phosphatidylcholines (PC),
      and ceramides, and in the erythrocyte membrane lipidome, mostly due to SMs, PEs
      and PCs. Already at 4 months, a separation in the serum lipidome was evident
      where SMs and PCs contributed. The separation was not detected at 12 months.
      CONCLUSIONS: The effect of MFGM supplementation on the lipidome is likely part of
      the mechanisms behind the positive cognitive and immunological effects of feeding
      the EF previously reported in the same study population.

PMID- 30120404
TI  - In a pilot study, reduced fatty acid desaturase 1 function was associated with
      nonalcoholic fatty liver disease and response to treatment in children.
AB  - BACKGROUND: FADS1 gene encodes delta 5 desaturase, a rate-limiting enzyme in the
      metabolism of n-3 and n-6 polyunsaturated fatty acids (PUFAs). Minor alleles of
      FADS1 locus polymorphisms are associated with reduced FADS1 expression and intra
      hepatic fat accumulation. However, the relationship between FADS1 expression and
      pediatric nonalcoholic fatty liver disease (NAFLD) risk remains to be explored.
      METHODS: We analyzed FADS1 transcription levels and their association with intra
      hepatic fat and histology in children, and we performed pathway enrichment
      analysis on transcriptomic profiles associated with FADS1 polymorphisms. We also
      evaluated the weight of FADS1 alleles on the response to combined docosahexaenoic
      acid, choline, and vitamin E (DHA-CHO-VE) treatment. RESULTS: FADS1 mRNA level
      was significantly and inversely associated with intra-hepatic fat (p = 0.004),
      degree of steatosis (p = 0.03), fibrosis (p = 0.05), and NASH (p = 0.008) among
      pediatric livers. Transcriptomics demonstrated a significant enrichment of a
      number of pathways strongly related to NAFLD (e.g., liver damage, fibrosis, and
      hepatic stellate cell activation). Compared to children who are common allele
      homozygotes, children with FADS1 minor alleles had a greater reduction in
      steatosis, fibrosis, and NAFLD activity score after DHA-CHO-VE. CONCLUSION: This
      study suggests that decreased FADS1 expression may be associated with NAFLD in
      children but an increased response to DHA-CHO-VE.

PMID- 30120405
TI  - Hepatic fat content and bone mineral density in children with overweight/obesity.
AB  - OBJECTIVES: To examine the influence of non-alcoholic fatty liver disease (NAFLD)
      and hepatic fat content on bone mineral density (BMD), and to investigate whether
      the relationship between NAFLD and BMD is independent of lifestyle factors
      related to BMD. METHODS: Hepatic fat content (magnetic resonance imaging), BMD,
      lean mass index, total and abdominal fat mass (dual-energy-X-ray absorptiometry),
      moderate to vigorous physical activity (MVPA) (accelerometry), and calcium and
      vitamin D intake (two 24 h recalls) were measured in 115 children with
      overweight/obesity aged 10.6 +/- 1.1 years old. RESULTS: Children with NAFLD had
      lower BMD than children without NAFLD regardless of sex, puberty stage, lean mass
      index, fat mass, MVPA, and calcium and vitamin D intake (0.89 +/- 0.01 vs. 0.93
      +/- 0.01 g/cm2 for NAFLD and non-NAFLD, respectively, P < 0.01). Higher hepatic
      fat content was significantly associated with lower BMD regardless of confounders
      (adjusted P < 0.05). CONCLUSIONS: Findings of the current study suggest that
      hepatic fat accumulation is associated with decreased BMD independently of
      adiposity, and regardless of those lifestyle factors closely related to bone
      mineral accrual in children. These results may have implication in the clinical
      management of children with overweight/obesity given the high prevalence of
      pediatric NAFLD.

PMID- 30120406
TI  - Stoss therapy using fortified biscuit for vitamin D-deficient children: a novel
      treatment.
AB  - BACKGROUND: To evaluate the efficacy of stoss therapy using fortified biscuit for
      vitamin D-deficient children. METHODS: A total of 108 children aged 30-72 months
      with vitamin D deficiency were studied in a randomized single-blind clinical
      trial. The deficient children were assigned to three groups, namely, vitamin D
      fortified biscuit (BG), capsule vitamin D (CG), and ampoule vitamin D (AG).
      Capsules and biscuits containing 50,000 IU of cholecalciferol were consumed twice
      per week for 3 consecutive weeks. Ampoules with 300,000 IU of cholecalciferol
      were injected intramuscularly in a single dose. Three weeks after treatment,
      serum 25(OH)D concentrations were measured, and the three groups were compared.
      RESULTS: Each method of treatment could increase the mean serum 25(OH)D
      concentration to optimal level. Serum 25(OH)D concentrations >=100 ng/mL were
      observed in six children, including four from AG and two from CG (P = 0.09). The
      comparison of the mean serum 25(OH)D concentrations after treatment showed
      between ampoule and capsule (P = 0.3) and capsule and biscuit (P = 0.62) were
      insignificant; however, the ampoule and biscuit groups differed significantly (P
      = 0.012). CONCLUSION: Stoss therapy using fortified biscuit may be an effective
      way to improve compliance in children who cannot take capsules without adverse
      effects and may also be recommended for prevention purposes.

PMID- 30120407
TI  - The neurorestorative effect of human amniotic fluid stem cells on the chronic
      phase of neonatal hypoxic-ischemic encephalopathy in mice.
AB  - BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of
      cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells
      have a favorable effect on HIE. However, the efficacy of human amniotic fluid
      stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The
      aim of this study was to determine the neurorestorative effect of hAFS on the
      chronic phase of HIE. METHODS: hAFS were isolated from AF cells as CD117-positive
      cells. HI was induced in 9-day-old mice. Animals intranasally received hAFS or
      phosphate-buffered saline at 10 days post HI and were harvested for histological
      analysis after functional tests at 21 days post HI. We also implanted PKH26
      positive hAFS to assess their migration to the brain. Finally, we determined gene
      expressions of trophic factors in hAFS co-cultured with HI brain extract.
      RESULTS: hAFS improved sensorimotor deficits in HIE by gray and white matter
      restoration and neuroinflammation reduction followed by migration to the lesion.
      Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), hepatocyte
      growth factor (HGF), and stromal cell-derived factor-1 (SDF-1) gene expressions
      in hAFS were elevated when exposed to HI-induced brain extract. CONCLUSION: hAFS
      induced functional recovery by exerting neurorestorative effects in HIE mice,
      suggesting that intranasal administration of hAFS could be a novel treatment for
      HIE, especially in the chronic phase.

PMID- 30120409
TI  - Digital devices and continuous telemetry: opportunities for aligning psychiatry
      and neuroscience.

PMID- 30120408
TI  - Altered ErbB4 splicing and cortical parvalbumin interneuron dysfunction in
      schizophrenia and mood disorders.
AB  - Working memory requires the activity of parvalbumin (PV) interneurons in the
      dorsolateral prefrontal cortex (DLPFC). Impaired working memory and lower PV
      expression in the DLPFC are reported in schizophrenia and to a lesser degree in
      mood disorders. We previously proposed that activity-dependent PV expression is
      lower in schizophrenia due to a shift in the splicing of erb-b2 receptor tyrosine
      kinase 4 (ErbB4) transcripts from major to inactive minor variants that reduces
      excitatory drive to PV interneurons. Here, we tested the hypothesis that the
      degree of major-to-minor shift in ErbB4 splicing predicts the level of PV
      expression across schizophrenia and mood disorders. Levels of ErbB4 splice
      variants and PV mRNA were quantified by PCR in the DLPFC from 40 matched tetrads
      (N = 160 subjects) of schizophrenia, bipolar disorder (BD), major depressive
      disorder (MDD), and unaffected comparison subjects. Relative to unaffected
      comparison subjects, the magnitude of increases in minor variant levels and
      decreases in major variant levels was greatest in schizophrenia, intermediate in
      BD, and least in MDD. The same rank order was present for the magnitude of
      increases in the composite splicing score, which reflects the degree of major-to
      minor shift across all ErbB4 splice loci, and for the magnitude of deficient PV
      expression. Finally, the composite splicing score negatively predicted PV
      expression across all subject groups. Together, these findings demonstrate a
      shared relationship between ErbB4 splicing and PV expression and suggest that
      scaling of the major-to-minor shift in ErbB4 splicing may influence the severity
      of deficient PV interneuron activity across diagnoses.

PMID- 30120410
TI  - Oxytocin attenuates phencyclidine hyperactivity and increases social interaction
      and nucleus accumben dopamine release in rats.
AB  - The pituitary neuropeptide oxytocin promotes social behavior, and is a potential
      adjunct therapy for social deficits in schizophrenia and autism. Oxytocin may
      mediate pro-social effects by modulating monoamine release in limbic and cortical
      areas, which was investigated herein using in vivo microdialysis, after
      establishing a dose that did not produce accompanying sedative or
      thermoregulatory effects that could concomitantly influence behavior. The effects
      of oxytocin (0.03-0.3 mg/kg subcutaneous) on locomotor activity, core body
      temperature, and social behavior (social interaction and ultrasonic
      vocalizations) were examined in adult male Lister-hooded rats, using selective
      antagonists to determine the role of oxytocin and vasopressin V1a receptors.
      Dopamine and serotonin efflux in the prefrontal cortex and nucleus accumbens of
      conscious rats were assessed using microdialysis. 0.3 mg/kg oxytocin modestly
      reduced activity and caused hypothermia but only the latter was attenuated by the
      V1a receptor antagonist, SR49059 (1 mg/kg intraperitoneal). Oxytocin at 0.1
      mg/kg, which did not alter activity and had little effect on temperature,
      significantly attenuated phencyclidine-induced hyperactivity and increased social
      interaction between unfamiliar rats without altering the number or pattern of
      ultrasonic vocalizations. In the same rats, oxytocin (0.1 mg/kg) selectively
      elevated dopamine overflow in the nucleus accumbens, but not prefrontal cortex,
      without influencing serotonin efflux. Systemic oxytocin administration attenuated
      phencyclidine-induced hyperactivity and increased pro-social behavior without
      decreasing core body temperature and selectively enhanced nucleus accumbens
      dopamine release, consistent with activation of mesocorticolimbic circuits
      regulating associative/reward behavior being involved. This highlights the
      therapeutic potential of oxytocin to treat social behavioral deficits seen in
      psychiatric disorders such as schizophrenia.

PMID- 30120411
TI  - The miR-96 and RARgamma signaling axis governs androgen signaling and prostate
      cancer progression.
AB  - Expression levels of retinoic acid receptor gamma (NR1B3/RARG, encodes RARgamma)
      are commonly reduced in prostate cancer (PCa). Therefore, we sought to establish
      the cellular and gene regulatory consequences of reduced RARgamma expression, and
      determine RARgamma regulatory mechanisms. RARG shRNA approaches in non-malignant
      (RWPE-1 and HPr1-AR) and malignant (LNCaP) prostate models revealed that reducing
      RARgamma levels, rather than adding exogenous retinoid ligand, had the greatest
      impact on prostate cell viability and gene expression. ChIP-Seq defined the
      RARgamma cistrome, which was significantly enriched at active enhancers
      associated with AR binding sites. Reflecting a significant genomic role for
      RARgamma to regulate androgen signaling, RARgamma knockdown in HPr1-AR cells
      significantly regulated the magnitude of the AR transcriptome. RARgamma
      downregulation was explained by increased miR-96 in PCa cell and mouse models,
      and TCGA PCa cohorts. Biochemical approaches confirmed that miR-96 directly
      regulated RARgamma expression and function. Capture of the miR-96 targetome by
      biotin-miR-96 identified that RARgamma and a number of RARgamma interacting co
      factors including TACC1 were all targeted by miR-96, and expression of these
      genes were prominently altered, positively and negatively, in the TCGA-PRAD
      cohort. Differential gene expression analyses between tumors in the TCGA-PRAD
      cohort with lower quartile expression levels of RARG and TACC1 and upper quartile
      miR-96, compared to the reverse, identified a gene network including several
      RARgamma target genes (e.g., SOX15) that significantly associated with worse
      disease-free survival (hazard ratio 2.23, 95% CI 1.58 to 2.88, p = 0.015). In
      summary, miR-96 targets a RARgamma network to govern AR signaling, PCa
      progression and disease outcome.

PMID- 30120413
TI  - Arrestin recruitment to dopamine D2 receptor mediates locomotion but not
      incentive motivation.
AB  - The dopamine (DA) D2 receptor (D2R) is an important target for the treatment of
      neuropsychiatric disorders such as schizophrenia and Parkinson's disease.
      However, the development of improved therapeutic strategies has been hampered by
      our incomplete understanding of this receptor's downstream signaling processes in
      vivo and how these relate to the desired and undesired effects of drugs. D2R is a
      G protein-coupled receptor (GPCR) that activates G protein-dependent as well as
      non-canonical arrestin-dependent signaling pathways. Whether these effector
      pathways act alone or in concert to facilitate specific D2R-dependent behaviors
      is unclear. Here, we report on the development of a D2R mutant that recruits
      arrestin but is devoid of G protein activity. When expressed virally in "indirect
      pathway" medium spiny neurons (iMSNs) in the ventral striatum of D2R knockout
      mice, this mutant restored basal locomotor activity and cocaine-induced locomotor
      activity in a manner indistinguishable from wild-type D2R, indicating that
      arrestin recruitment can drive locomotion in the absence of D2R-mediated G
      protein signaling. In contrast, incentive motivation was enhanced only by wild
      type D2R, signifying a dissociation in the mechanisms that underlie distinct D2R
      dependent behaviors, and opening the door to more targeted therapeutics.

PMID- 30120414
TI  - Are there two different forms of functional dystonia? A multimodal brain
      structural MRI study.
AB  - This study assessed brain structural alterations in two diverse clinical forms of
      functional (psychogenic) dystonia (FD) - the typical fixed dystonia (FixFD)
      phenotype and the "mobile" dystonia (MobFD) phenotype, which has been recently
      described in one study. Forty-four FD patients (13 FixFD and 31 MobFD) and 43
      healthy controls were recruited. All subjects underwent 3D T1-weighted and
      diffusion tensor (DT) magnetic resonance imaging (MRI). Cortical thickness,
      volumes of gray matter (GM) structures, and white matter (WM) tract integrity
      were assessed. Normal cortical thickness in both FD patient groups compared with
      age-matched healthy controls were found. When compared with FixFD, MobFD patients
      showed cortical thinning of the left orbitofrontal cortex, and medial and lateral
      parietal and cingulate regions bilaterally. Additionally, compared with controls,
      MobFD patients showed reduced volumes of the left nucleus accumbens, putamen,
      thalamus, and bilateral caudate nuclei, whereas MobFD patients compared with
      FixFD demonstrated atrophy of the right hippocampus and globus pallidus. Compared
      with both controls and MobFD cases, FixFD patients showed a severe disruption of
      WM architecture along the corpus callous, corticospinal tract, anterior thalamic
      radiations, and major long-range tracts bilaterally. This study showed different
      MRI patterns in two variants of FD. MobFD had alterations in GM structures
      crucial for sensorimotor processing, emotional, and cognitive control. On the
      other hand, FixFD patients were characterized by a global WM disconnection
      affecting main sensorimotor and emotional control circuits. These findings may
      have important implications in understanding the neural substrates underlying
      different phenotypic FD expression levels.

PMID- 30120412
TI  - Visual Processing by Calretinin Expressing Inhibitory Neurons in Mouse Primary
      Visual Cortex.
AB  - Inhibition in the cerebral cortex is delivered by a variety of GABAergic
      interneurons. These cells have been categorized by their morphology, physiology,
      gene expression and connectivity. Many of these classes appear to be conserved
      across species, suggesting that the classes play specific functional roles in
      cortical processing. What these functions are, is still largely unknown. The
      largest group of interneurons in the upper layers of mouse primary visual cortex
      (V1) is formed by cells expressing the calcium-binding protein calretinin (CR).
      This heterogeneous class contains subsets of vasoactive intestinal polypeptide
      (VIP) interneurons and somatostatin (SOM) interneurons. Here we show, using in
      vivo two-photon calcium imaging in mice, that CR neurons can be sensitive to
      stimulus orientation, but that they are less selective on average than the
      overall neuronal population. Responses of CR neurons are suppressed by a
      surrounding stimulus, but less so than the overall population. In rats and
      primates, CR interneurons have been suggested to provide disinhibition, but we
      found that in mice their in vivo activation by optogenetics causes a net
      inhibition of cortical activity. Our results show that the average functional
      properties of CR interneurons are distinct from the averages of the parvalbumin,
      SOM and VIP interneuron populations.

PMID- 30120415
TI  - 5-HT2C receptor blockade reverses SSRI-associated basal ganglia dysfunction and
      potentiates therapeutic efficacy.
AB  - Serotonin (5-HT) selective reuptake inhibitors (SSRIs) are widely used in the
      treatment of depression and anxiety disorders, but responsiveness is uncertain
      and side effects often lead to discontinuation. Side effect profiles suggest that
      SSRIs reduce dopaminergic (DAergic) activity, but specific mechanistic insight is
      missing. Here we show in mice that SSRIs impair motor function by acting on 5
      HT2C receptors in the substantia nigra pars reticulata (SNr), which in turn
      inhibits nigra pars compacta (SNc) DAergic neurons. SSRI-induced motor deficits
      can be reversed by systemic or SNr-localized 5-HT2C receptor antagonism. SSRIs
      induce SNr hyperactivity and SNc hypoactivity that can also be reversed by
      systemic 5-HT2C receptor antagonism. Optogenetic inhibition of SNc DAergic
      neurons mimics the motor deficits due to chronic SSRI treatment, whereas local
      SNr 5-HT2C receptor antagonism or optogenetic activation of SNc DAergic neurons
      reverse SSRI-induced motor deficits. Lastly, we find that 5-HT2C receptor
      antagonism potentiates the antidepressant and anxiolytic effects of SSRIs.
      Together our findings demonstrate opposing roles for 5-HT2C receptors in the
      effects of SSRIs on motor function and affective behavior, highlighting the
      potential benefits of 5-HT2C receptor antagonists for both reduction of motor
      side effects of SSRIs and augmentation of therapeutic antidepressant and
      anxiolytic effects.

PMID- 30120416
TI  - Endosomal sorting and trafficking, the retromer complex and neurodegeneration.
AB  - The retromer is a highly conserved multimeric protein complex present in all
      eukaryotic cells whose activity is essential for regulating the recycling and
      retrieval of numerous protein cargos from the endosome to trans-Golgi network or
      the cell surface. In recent years, molecular and genomic studies have provided
      evidence that aberrant regulation of endosomal protein sorting and trafficking
      secondary to a dysfunction of the retromer complex could be implicated in the
      pathogenesis of several neurodegenerative diseases. Thus, deficiency or mutations
      in one or more protein components of the retromer leads to increased accumulation
      of protein aggregates, as well as enhanced cellular neurotoxicity. In this
      review, we will discuss the structure and function of the retromer complex and
      its neurobiology, its relevance to key molecules involved in neurodegeneration
      and the potential role that it plays in the development of two major
      neurodegenerative disorders, Parkinson's disease and Alzheimer's disease.
      Finally, we will discuss the viability of targeting the retromer via
      pharmacological chaperones or genetic approaches to enhance or restore its
      function as a novel and unifying disease-modifying strategy against these
      diseases.

PMID- 30120417
TI  - 18F-FIBT may expand PET for beta-amyloid imaging in neurodegenerative diseases.
AB  - 18F-FIBT, 2-(p-Methylaminophenyl)-7-(2-[18F]fluoroethoxy)imidazo-[2,1
      b]benzothiazole, is a new selective PET tracer under clinical investigation to
      specifically image beta-amyloid depositions (Abeta) in humans in-vivo that binds
      to Abeta with excellent affinity (Kd 0.7 +/- 0.2) and high selectivity over tau
      and alpha-synuclein aggregates (Ki > 1000 nM). We aimed to characterize 18F-FIBT
      in a series of patients with different clinical-pathophysiological phenotypes and
      to compare its binding characteristics to the reference compound PiB. Six
      patients (mild late-onset and moderate early-onset AD dementia, mild cognitive
      impairment due to AD, intermediate likelihood, mild behavioral variant of
      frontotemporal dementia, subjective memory impairment without evidence of
      neurodegeneration, and mild dementia due to Posterior Cortical Atrophy) underwent
      PET imaging with 18F-FIBT on PET/MR. With the guidance of MRI, PET images were
      corrected for partial volume effect, time-activity curves (TACs) of regions of
      interest (ROIs) were extracted, and non-displaceable binding potentials (BPnd),
      standardized uptake value ratios (SUVR), and distribution volume ratio (DVR) were
      compared. Specific binding was detected in the cases with evidence of the AD
      pathophysiological process visualized in images of BPnd, DVR and SUVR,
      consistently with patterns of different tracers in previous studies. SUVR showed
      the highest correlation with clinical severity. The previous preclinical
      characterization and the results of this case series suggest the clinical
      usefulness of FIBT as a selective and highly affine next-generation 18F-labeled
      tracer for amyloid-imaging with excellent pharmacokinetics in the diagnosis of
      neurodegenerative diseases. The results compare well to the gold standard PiB and
      hence support further investigation in larger human samples.

PMID- 30120418
TI  - Cholinergic regulation of mood: from basic and clinical studies to emerging
      therapeutics.
AB  - Mood disorders are highly prevalent and are the leading cause of disability
      worldwide. The neurobiological mechanisms underlying depression remain poorly
      understood, although theories regarding dysfunction within various
      neurotransmitter systems have been postulated. Over 50 years ago, clinical
      studies suggested that increases in central acetylcholine could lead to depressed
      mood. Evidence has continued to accumulate suggesting that the cholinergic system
      has a important role in mood regulation. In particular, the finding that the
      antimuscarinic agent, scopolamine, exerts fast-onset and sustained antidepressant
      effects in depressed humans has led to a renewal of interest in the cholinergic
      system as an important player in the neurochemistry of major depression and
      bipolar disorder. Here, we synthesize current knowledge regarding the modulation
      of mood by the central cholinergic system, drawing upon studies from human
      postmortem brain, neuroimaging, and drug challenge investigations, as well as
      animal model studies. First, we describe an illustrative series of early
      discoveries which suggest a role for acetylcholine in the pathophysiology of mood
      disorders. Then, we discuss more recent studies conducted in humans and/or
      animals which have identified roles for both acetylcholinergic muscarinic and
      nicotinic receptors in different mood states, and as targets for novel therapies.

PMID- 30120419
TI  - Dendritic remodeling of D1 neurons by RhoA/Rho-kinase mediates depression-like
      behavior.
AB  - Depression alters the structure and function of brain reward circuitry.
      Preclinical evidence suggests that medium spiny neurons (MSNs) in the nucleus
      accumbens (NAc) undergo structural plasticity; however, the molecular mechanism
      and behavioral significance is poorly understood. Here we report that atrophy of
      D1, but not D2 receptor containing MSNs is strongly associated with social
      avoidance in mice subject to social defeat stress. D1-MSN atrophy is caused by
      cell-type specific upregulation of the GTPase RhoA and its effector Rho-kinase.
      Pharmacologic and genetic reduction of activated RhoA prevents depressive
      outcomes to stress by preventing loss of D1-MSN dendritic arbor. Pharmacologic
      and genetic promotion of activated RhoA enhances depressive outcomes by reducing
      D1-MSN dendritic arbor and is sufficient to promote depressive-like behaviors in
      the absence of stress. Chronic treatment with Rho-kinase inhibitor Y-27632 after
      chronic social defeat stress reverses depression-like behaviors by restoring D1
      MSN dendritic complexity. Taken together, our data indicate functional roles for
      RhoA and Rho-kinase in mediating depression-like behaviors via dendritic
      remodeling of NAc D1-MSNs and may prove a useful target for new depression
      therapeutics.

PMID- 30120421
TI  - Protective effects of elevated anandamide on stress and fear-related behaviors:
      translational evidence from humans and mice.
AB  - Post-traumatic stress disorder (PTSD) is a common, debilitating condition with
      limited treatment options. Extinction of fear memories through prolonged exposure
      therapy, the primary evidence-based behavioral treatment for PTSD, has only
      partial efficacy. In mice, pharmacological inhibition of fatty acid amide
      hydrolase (FAAH) produces elevated levels of anandamide (AEA) and promotes fear
      extinction, suggesting that FAAH inhibitors may aid fear extinction-based
      treatments. A human FAAH 385C->A substitution encodes an FAAH enzyme with reduced
      catabolic efficacy. Individuals homozygous for the FAAH 385A allele may therefore
      offer a genetic model to evaluate the impact of elevations in AEA signaling in
      humans, helping to inform whether FAAH inhibitors have the potential to
      facilitate fear extinction therapy for PTSD. To overcome the challenge posed by
      low frequency of the AA genotype (appr. 5%), we prospectively genotyped 423
      individuals to examine the balanced groups of CC, AC, and AA individuals (n =
      25/group). Consistent with its loss-of-function nature, the A allele was dose
      dependently associated with elevated basal AEA levels, facilitated fear
      extinction, and enhanced the extinction recall. Moreover, the A-allele
      homozygotes were protected against stress-induced decreases in AEA and negative
      emotional consequences of stress. In a humanized mouse model, AA homozygous mice
      were similarly protected against stress-induced decreases in AEA, both in the
      periphery, and also in the amygdala and prefrontal cortex, brain structures
      critically involved in fear extinction and regulation of stress responses.
      Collectively, these data suggest that AEA signaling can temper aspects of the
      stress response and that FAAH inhibition may aid the treatment for stress-related
      psychiatric disorders, such as PTSD.

PMID- 30120422
TI  - Ductus arteriosus outcome with focus on the initially patent but hemodynamically
      insignificant ductus in preterm neonates.
AB  - BACKGROUND/OBJECTIVES: The hemodynamically insignificant (hisPDA) ductus
      arteriosus often progresses to hemodynamic significance. In this review, we
      sought risk factors predictive of progression. METHODS: Early hisPDAs were
      subdivided into those that closed spontaneously vs. those that progressed to
      hsPDA. RESULTS: Sixty percent of early hisPDAs subsequently progressed to hsPDAs.
      In all but one, the ductus never closed, but rather became progressively more
      significant over time. The echocardiographic parameters best associated with
      subsequent progression were an increased transductal diameter (1.81 +/- 0.77 vs.
      1.21 +/- 0.44 mm; p < 0.001) and the presence of diastolic flow reversal. ROC
      curve analysis showed that the best ductal diameter criterion for predicting the
      progression to hsPDA was >1.4 (sensitivity = 91; specificity = 81). The combined
      morbidity score was higher in those infants who progressed to hsPDA as compared
      with those who did not (p = 0.0038). CONCLUSIONS: Increased ductal diameter and
      diastolic flow reversal on the first echocardiogram were best correlated with
      progression of hisPDA to hsPDA.

PMID- 30120420
TI  - Identification of novel loci associated with infant cognitive ability.
AB  - It is believed that genetic factors play a large role in the development of many
      cognitive and neurological processes; however, epidemiological evidence for the
      genetic basis of childhood neurodevelopment is very limited. Identification of
      the genetic polymorphisms associated with early-stage neurodevelopment will help
      elucidate biological mechanisms involved in neuro-behavior and provide a better
      understanding of the developing brain. To search for such variants, we performed
      a genome-wide association study (GWAS) for infant mental and motor ability at two
      years of age with mothers and children recruited from cohorts in Bangladesh and
      Mexico. Infant ability was assessed using mental and motor composite scores
      calculated with country-specific versions of the Bayley Scales of Infant
      Development. A missense variant (rs1055153) located in the gene WWTR1 reached
      genome-wide significance in association with mental composite score (meta
      analysis effect size of minor allele betameta = -6.04; 95% CI: -8.13 to -3.94; P
      = 1.56*10-8). Infants carrying the minor allele reported substantially lower
      cognitive scores in both cohorts, and this variant is predicted to be in the top
      0.3% of most deleterious substitutions in the human genome. Fine mapping and
      region-based association testing provided additional suggestive evidence that
      both WWTR1 and a second gene, LRP1B, were associated with infant cognitive
      ability. Comparisons with recently conducted GWAS in intelligence and educational
      attainment indicate that our phenotypes do not possess a high genetic correlation
      with either adolescent or adult cognitive traits, suggesting that infant
      neurological assessments should be treated as an independent outcome of interest.
      Additional functional studies and replication efforts in other cohorts may help
      uncover new biological pathways and genetic architectures that are crucial to the
      developing brain.

PMID- 30120423
TI  - Effect of reading to preterm infants on measures of cardiorespiratory stability
      in the neonatal intensive care unit.
AB  - OBJECTIVE: To evaluate the impact of parental bedside reading (PR) on cardio
      respiratory (CR) stability of preterm infants. METHODS/STUDY DESIGN: Prospective
      examination of the impact of PR on CR stability in preterm NICU infants. CR data
      from 3 time points: pre-reading (3 and 1 h before reading), during PR, and post
      reading (1 h after reading) were compared. RESULTS: Eighteen infants born at 23
      31wks gestation, and 8 to 56 days old, were enrolled. Episodes of oxygen
      desaturation to <85% were fewer during PR as compared to the pre-reading periods
      and were fewer with live and maternal PR. CONCLUSION: Preterm infants showed
      fewer desaturation events less than 85% during PR than prior to reading exposure.
      This effect persisted up to 1 h after reading exposure. Desaturation events were
      fewer with live and maternal PR. Voice exposure can be an important way for
      parents to participate in the care of their preterm infants.

PMID- 30120424
TI  - Transcutaneous bilirubinometer use and practices surrounding jaundice in 150
      California newborn intensive care units.
AB  - OBJECTIVES: Transcutaneous bilirubin measurements (TcBs) provide a noninvasive
      method for screening infants for hyperbilirubinemia and have been used
      extensively in term and late preterm newborns in well baby nurseries, offices,
      and outpatient clinics. Several studies have also demonstrated the utility of
      TcBs as a screening tool for infants > 28 weeks' gestation and their ability to
      reduce the need for blood sampling. The objectives of this study are to identify
      how often TcBs are used among California Newborn Intensive Care Units (NICUs) in
      preterm, late preterm and term infants, and other aspects of jaundice management.
      METHODS: We conducted a survey on TcB use and practices relating to jaundice
      management in 150 California NICUs between April and October 2016. RESULTS: TcB
      screening is routinely used in 28% (42/150) of NICUs. Only 7% (11/150) of NICUs
      use TcB in preterm infants < 28 weeks. Practice varied similarly across NICU
      levels of care. Among the subset of NICUs that responded to questions related to
      phototherapy and screening practices, prophylactic phototherapy was used in 38%
      (23/59) and 90% (55/61) screened for glucose-6-phosphate dehydrogenase deficiency
      based on race, ethnicity, and/or family history. CONCLUSION(S): Despite studies
      validating the accuracy of TcB in preterm infants > 28 weeks, only 28% of
      California NICUs routinely use TcB devices. TcB screening in infants < 28 weeks
      gestation is not widely used and no recommendation can be made in this regard
      until there is more experience with its application using a standardized protocol
      in these infants and on a large scale.

PMID- 30120425
TI  - Understanding the complexity of glycaemic health: systematic bio-psychosocial
      modelling of fasting glucose in middle-age adults; a DynaHEALTH study.
AB  - BACKGROUND: The prevention of the risk of type 2 diabetes (T2D) is complicated by
      multidimensional interplays between biological and psychosocial factors acting at
      the individual level. To address the challenge we took a systematic approach, to
      explore the bio-psychosocial predictors of blood glucose in mid-age. METHODS:
      Based on the 31-year and 46-year follow-ups (5,078 participants, 43% male) of
      Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio
      psychosocial variables at 31 years to enable a data-driven approach. As selection
      criteria, the variable must be (i) a component of the metabolic syndrome or an
      indicator of psychosocial health using WHO guidelines, (ii) easily obtainable in
      general health check-ups and (iii) associated with fasting blood glucose at 46
      years (P < 0.10). Exploratory and confirmatory factor analysis were used to
      derive latent factors, and stepwise linear regression allowed exploration of
      relationships between factors and fasting glucose. RESULTS: Of all 26 variables
      originally considered, 19 met the selection criteria and were included in an
      exploratory factor analysis. Two variables were further excluded due to low
      loading (<0.3). We derived four latent factors, which we named as socioeconomic,
      metabolic, psychosocial and blood pressure status. The combination of metabolic
      and psychosocial factors, adjusted for sex, provided best prediction of fasting
      glucose at 46 years (explaining 10.7% of variation in glucose; P < 0.001).
      Regarding different bio-psychosocial pathways and relationships, the importance
      of psychosocial factors in addition to established metabolic risk factors was
      highlighted. CONCLUSIONS: The present study supports evidence for the bio
      psychosocial nature of adult glycemic health and exemplifies an evidence-based
      approach to model the bio-psychosocial relationships. The factorial model may
      help further research and public health practice in focusing also on psychosocial
      aspects in maintaining normoglycaemia in the prevention of cardio-metabolic
      diseases.

PMID- 30120426
TI  - Visceral adiposity and insular networks: associations with food craving.
AB  - BACKGROUND/OBJECTIVES: Accumulation of visceral adiposity can disrupt the brain's
      sensitivity to interoceptive feedback, which is coded in the insula. This study
      aimed to test the link between visceral fat and the functional connectivity of
      two insulae regions relevant for eating behavior: the middle-dorsal insula
      (mIns), which codes homeostatic changes, and the rostral insula (rIns), which
      codes stable representations of food properties. We also assessed the impact of
      visceral adiposity-associated insulae networks on food craving. SUBJECTS/METHODS:
      Seventy-five adults ranging in weight status (normal and excess weight) underwent
      resting-state functional magnetic resonance imaging (fMRI) and subjective food
      craving measures. We examined the association between visceral fat and seed-based
      functional connectivity of the mIns and the rIns, controlling for BMI, age, and
      sex, using multiple regressions in SPM8. We also tested if visceral fat mediated
      the association between insulae connectivity and food craving. RESULTS: Higher
      visceral adiposity was associated with decreased connectivity between the mIns
      and a cluster involving the hypothalamus and the bed nucleus of the stria
      terminalis. Decreased connectivity in this network was associated with greater
      food craving, a relation mediated by visceral adiposity. Visceral adiposity was
      also associated with increased connectivity between the mIns and the middle
      frontal gyri and the right intraparietal cortex, and between the rIns and the
      right amygdala. CONCLUSIONS: Accumulation of visceral adiposity is linked to
      disrupted functional connectivity within the mIns and rIns networks. Furthermore,
      the link between the mIns network and food craving is mediated by visceral fat.
      Findings suggest that visceral fat disrupts insula coding of bodily homeostatic
      signals, which may boost externally driven food cravings.

PMID- 30120427
TI  - The impact of rising food prices on obesity in women: a longitudinal analysis of
      31 low-income and middle-income countries from 2000 to 2014.
AB  - OBJECTIVES: To examine whether changes in food prices are associated with changes
      in obesity prevalence among women in developing countries, and assess effect
      modification by individual socioeconomic status (SES). METHODS: Longitudinal
      study of country-level food price inflation temporally and geographically linked
      to anthropometric data on non-pregnant adult women (n = 295,984) in 31 low-income
      and middle-income countries over the 2000-2014 time period, using separate
      multivariable multilevel growth models of five SES indicators. Post-estimation
      analysis computed the relationship between food price inflation and predicted
      mean probabilities of being obese, by SES. RESULTS: Rising food price inflation
      was strongly associated with women's obesity prevalence, and SES consistently
      modified the relationship. Regardless of indicator used, higher food price
      inflation was positively associated with obesity among women in top SES
      categories, but was flat or negative among women in low SES categories, averaging
      over time. The SES differences were widest across educational strata and were
      most pronounced when food price inflation was highest. Overall, for every 1-unit
      increase in food price inflation, predicted mean obesity prevalence was between
      0.02 and 0.06 percentage points greater in women of high SES compared to low SES
      women. CONCLUSION: There is a strong link between food price inflation and
      obesity in adult women in developing countries which is clearly modified by
      individuals' SES. Greater food price inflation was associated with greater
      obesity prevalence only among women in higher SES groups, who may be net food
      buyers most at risk of obesity in low-income and middle-income countries.

PMID- 30120429
TI  - Single-nucleotide polymorphisms in a cohort of significantly obese women without
      cardiometabolic diseases.
AB  - BACKGROUND/OBJECTIVES: Obesity is an important risk factor for the development of
      diseases such as diabetes mellitus, hypertension, and dyslipidemia; however, a
      small number of individuals with long-standing obesity do not present with these
      cardiometabolic diseases. Such individuals are referred to as metabolically
      healthy obese (MHO) and potentially represent a subgroup of the general
      population with a protective genetic predisposition to obesity-related diseases.
      We hypothesized that individuals who were metabolically healthy, but
      significantly obese (BMI >= 35 kg/m2) would represent a highly homogenous
      subgroup, with which to investigate potential genetic associations to obesity. We
      further hypothesized that such a cohort may lend itself well to investigate
      potential genotypes that are protective with respect to the development of
      cardiometabolic disease. SUBJECTS/METHODS: In the present study, we implemented
      this novel selection strategy by screening 892 individuals diagnosed as Class 2
      or Class 3 obese and identified 38 who presented no manifestations of
      cardiometabolic disease. We then assessed these subjects for single-nucleotide
      polymorphisms (SNPs) that associated with this phenotype. RESULTS: Our analysis
      identified 89 SNPs that reach statistical significance (p < 1 * 10-5), some of
      which are associated with genes of biological pathways that influences dietary
      behavior; others are associated with genes previously linked to obesity and
      cardiometabolic disease as well as neuroimmune disease. This study, to the best
      of our knowledge, represents the first genetic screening of a cardiometabolically
      healthy, but significantly obese population.

PMID- 30120428
TI  - Predictive utility of childhood anthropometric measures on adult glucose
      homeostasis measures: a 20-year cohort study.
AB  - BACKGROUND/OBJECTIVES: Childhood body mass index (BMI) predicts adult glucose
      homeostasis measures and type 2 diabetes mellitus, but little is known about the
      predictive utility of other anthropometric measures in childhood. We aimed to
      identify the anthropometric measure in childhood that best predicts adult glucose
      homeostasis measures and examine if the combination of additional anthropometric
      measures further improves predictive utility. METHODS: A 20-year follow-up of
      children participating in the Childhood Determinants of Adult Health Study (n =
      2345, aged 7-15 years at baseline). Baseline anthropometric measures were waist
      circumference (WC), WC adjusted for height, weight adjusted for height, hip
      circumference, waist-hip-ratio, waist-height-ratio, BMI, conicity index,
      abdominal volume index (AVI), body adiposity index, and a body shape index.
      Fasting glucose and insulin levels measured at follow-up were used to define
      insulin resistance (HOMA2-IR), low beta-cell function (HOMA2-beta), high fasting
      insulin, and impaired fasting glucose (IFG). RESULTS: All child anthropometric
      measures were significantly associated with HOMA2-IR, HOMA2-beta, and high
      fasting insulin (relative risk = 1.12-1.55), but not IFG. AVI had the largest
      area under receiver-operating curve (AUC) in predicting adult HOMA2-IR (AUC, 95%
      confidence interval: 0.610, 0.584-0.637), HOMA2-beta (0.615, 0.588-0.642) and
      high fasting insulin (0.613, 0.587-0.639). Combining each additional
      anthropometric measure with AVI did not appreciably increase predictive utility
      (an increase of 0.001-0.002 in AUC, p > 0.05 for all). CONCLUSIONS:
      Anthropometric measures from a single time-point in childhood are associated with
      insulin-related outcomes 20-year later in adulthood. However, overall predictive
      utility was low and was not substantially enhanced by combining multiple
      different child anthropometric measures.

PMID- 30120431
TI  - Repeat length variations in polyglutamine disease-associated genes affect body
      mass index.
AB  - BACKGROUND: The worldwide prevalence of obesity, a major risk factor for numerous
      debilitating chronic disorders, is increasing rapidly. Although a substantial
      amount of the variation in body mass index (BMI) is estimated to be heritable,
      the largest meta-analysis of genome-wide association studies (GWAS) to date
      explained only ~2.7% of the variation. To tackle this 'missing heritability'
      problem of obesity, here we focused on the contribution of DNA repeat length
      polymorphisms which are not detectable by GWAS. SUBJECTS AND METHODS: We
      determined the cytosine-adenine-guanine (CAG) repeat length in the nine known
      polyglutamine disease-associated genes (ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP,
      HTT, ATN1 and AR) in two large cohorts consisting of 12,457 individuals and
      analyzed their association with BMI, using generalized linear mixed-effect
      models. RESULTS: We found a significant association between BMI and the length of
      CAG repeats in seven polyglutamine disease-associated genes (including ATXN1,
      ATXN2, ATXN3, CACNA1A, ATXN7, TBP and AR). Importantly, these repeat variations
      could account for 0.75% of the total BMI variation. CONCLUSIONS: Our findings
      incriminate repeat polymorphisms as an important novel class of genetic risk
      factors of obesity and highlight the role of the brain in its pathophysiology.

PMID- 30120432
TI  - Quality of Life across Mental Disorders in Psychiatric Outpatients.
AB  - INTRODUCTION: Literature has shown that individuals with various psychiatric
      disorders experience a lower quality of life (QoL). However, few have examined
      QoL across disorders. The current study explored differences in QoL and symptom
      severity across 4 psychiatric diagnostic groups: anxiety disorders (including
      obsessive compulsive disorder [OCD]), depressive disorders, schizophrenia, and
      pathological gambling. MATERIALS AND METHODS: Data analysed was from a previous
      study that examined the prevalence of hoarding symptoms among outpatients (n =
      500) in a tertiary psychiatric hospital in Singapore. Measures utilised included
      the Beck Anxiety Inventory (BAI), Beck Depression Inventory-II (BDI-II) and
      Quality of Life Enjoyment and Satisfaction QuestionnaireShort Form (Q-LES-Q-SF).
      Sociodemographic information and details on type and number of comorbidities were
      also collected. RESULTS: The depressive disorder group had the highest level of
      depressive and anxiety symptoms and the lowest QoL whereas; the schizophrenia
      group had the lowest level of depressive symptoms and the highest QoL. Age and
      employment status were the only sociodemographic correlates which were
      significantly associated with QoL. After controlling for sociodemographic
      factors, only the type of mental disorder was found to have a significant effect
      in explaining BAI, BDI-II and Q-LES-Q-SF. CONCLUSION: Findings offer insight in
      terms of the burden associated with the various disorders.

PMID- 30120430
TI  - Socioeconomic inequalities in weight, height and body mass index from birth to 5
      years.
AB  - BACKGROUND/OBJECTIVES: Studies in high-income countries show that despite the
      positive association of weight with socioeconomic position at birth, an inverse
      socioeconomic gradient in overweight (OW) appears later in childhood. The
      objectives were to understand the natural history of socioeconomic inequalities
      in weight, height and body mass index (BMI), by investigating their associations
      with maternal educational level between birth and 5 years, separately in boys and
      girls. SUBJECTS/METHODS: A published work of growth modelling between birth and 5
      years allowed us to calculate predicted weight, height and BMI at 1 month, 6
      months, 1, 3 and 5 years for 1735 children from the French EDEN mother-child
      cohort. Associations between maternal education and predicted measures of body
      size were analysed with marginal linear and logistic models, stratified by sex.
      RESULTS: In girls, despite a positive association between maternal education and
      birthweight, an inverse socioeconomic gradient was observed as early as 1 month
      for BMI. Girls whose mothers had low education levels were shorter on the whole
      than their counterparts with better-educated mothers, despite their similar
      weights. In boys, no socioeconomic gradient in BMI was observed at any age,
      including birth, but positive associations were found as early as 1 month for
      both weight and height. CONCLUSIONS: The emergence of an inverse socioeconomic
      gradient in BMI and OW apparently results from a complex pattern of socioeconomic
      inequalities in weight and height from 1 month onwards. The very start of life
      thus appears to be an important window of opportunity for addressing
      socioeconomic inequalities in growth.

PMID- 30120434
TI  - Arrival of Candida auris Fungus in Singapore: Report of the First 3 Cases.

PMID- 30120433
TI  - The Prevalence and Severity of Myopia among Suburban Schoolchildren in Taiwan.
AB  - INTRODUCTION: We aimed to determine the prevalence and severity of myopia in
      suburban schoolchildren. The refractive error, best corrected visual acuity
      (BCVA) and other ocular indices of 6069 schoolchildren (aged 6 to 15 years) from
      elementary and junior high schools in Chiayi County, Taiwan were examined in 2013
      2015. MATERIALS AND METHODS: Spherical equivalent (SE) was stratified into 4
      categories: emmetropia, mild myopia, moderate myopia, and high myopia for
      underlying analysis. Chi-squared (chi2) tests were used to determine significant
      associations between myopia and BCVA and age levels. To compare statistical
      significance among different age levels, P values of Bonferroni tests were
      calculated. Receiver operating characteristic (ROC) curves and correlation
      coefficient were calculated to assess the correlation between myopia and each
      ocular index. RESULTS: The youngest subject diagnosed with myopia was a 7-year
      old. Myopia had significant associations with both BCVA and age levels (95%
      confidence intervals [CI] = 2.553, 2.713 and -0.284, -0.248, respectively), under
      P <0.05. Among the calculated ROC values, BCVA had the highest area of 0.676 with
      myopia. This further confirmed that BCVA was highly correlated with myopia in
      schoolchildren. Other ocular indices like intraocular pressure (IOP), pupil
      distance, ocular alignments, or ocular height had ROC curves below 0.5 to myopia.
      CONCLUSION: This study concluded that the onset of myopia started earlier and
      progressively worsened with years of investigation among the suburban
      schoolchildren. Myopia had significant associations with BCVA and age levels. To
      effectively reduce the prevalence and severity of myopia, it is time to take
      actions on eye care education for suburban schoolchildren.

PMID- 30120435
TI  - Camera Cover Perforation after Arthroscopic Surgery.

PMID- 30120436
TI  - Delusion of Parasitosis: A Descriptive Analysis of 88 Patients at a Tertiary Skin
      Centre.

PMID- 30120437
TI  - An Unexpected Cause of Trauma-related Myocardial Infarction: Multimodality
      Assessment of Right Coronary Artery Dissection.

PMID- 30120438
TI  - Multiple Erythematous Plaques with Palpable Purpura in a Febrile Patient.

PMID- 30120440
TI  - Correction: Outcomes of Dabigatran and Warfarin for Atrial Fibrillation.

PMID- 30120439
TI  - A Case Study Using a Multimodal Approach to Melodic Intonation Therapy.
AB  - Purpose: The purpose of this study was to assess the efficacy. of increasing
      spontaneous expressive language using a modified melodic intonation therapy (MIT)
      approach with a male participant diagnosed with acquired aphasia and apraxia who
      was 10 years post onset. Method: A therapeutic protocol consisting of vocal and
      linguistic tasks was administered. The participant attended two 50-min individual
      sessions and a 4-hr/week socialization program for three 12-week semesters.
      Measures of speech and language were administered before intervention and at the
      completion of each of the 3 semesters. Results: At the completion of the study,
      the participant demonstrated reduced apraxia of speech as measured by The Apraxia
      Battery for Adults, Second Edition (Dabul, 2000). He also showed improvements in
      auditory comprehension skills as measured on the Boston Diagnostic Aphasia
      Evaluation (Goodglass, Kaplan, & Barresi, 2000). His spontaneous utterances were
      characterized by an increased number of complete sentences and questions. Several
      language parameters including mean length of utterance, total number of
      spontaneous (untrained) utterances, and number of different words spoken were
      also improved as revealed through language analysis. Conclusions: Integration of
      melodic intonation therapy through the addition of musical elements may result in
      improved speech and expressive language skills when administered over a 9-month
      period in conjunction with a group socialization program.

PMID- 30120441
TI  - Statistical Learning: How it Relates to Speech-Language Pathology.
AB  - Purpose: The purpose of this special issue is to introduce speech-language
      pathologists to the topic of statistical learning and how this is relevant to
      their practice. In the following articles, the concept of statistical learning
      will be explained, and readers will find (a) research studies showing how
      children with special needs can use statistical learning to learn language; (b)
      tutorials that show why statistical learning is meaningful for special
      populations; and (c) tutorials that show how statistical learning is involved in
      language, reading, and spelling.

PMID- 30120442
TI  - Reading as Statistical Learning.
AB  - Purpose: The purpose of this tutorial is to explain how learning to read can be
      thought of as learning statistical regularities and to demonstrate why this is
      relevant for theory, modeling, and practice. This tutorial also shows how
      triangulation of methods and cross-linguistic research can be used to gain
      insight. Method: The impossibility of conveying explicitly all of the
      regularities that children need to acquire in a deep orthography, such as
      English, can be demonstrated by examining lesser-known probabilistic orthographic
      cues to lexical stress. Detection of these kinds of cues likely occurs via a type
      of implicit learning known as statistical learning (SL). The first part of the
      tutorial focuses on these points. Next, studies exploring how individual
      differences in the capacity for SL relate to variability in word reading accuracy
      in the general population are discussed. A brief overview of research linking
      impaired SL and dyslexia is also provided. The final part of the tutorial focuses
      on how we might supplement explicit literacy instruction with implicit learning
      methods and emphasizes the value of testing the efficacy of new techniques in the
      classroom. The basic and applied research reviewed here includes corpus analyses,
      behavioral testing, computational modeling, and classroom-based research.
      Although some of these methods are not commonly used in clinical research, the
      depth and breadth of this body of work provide a compelling case for why reading
      can be thought of as SL and how this view can inform practice. Conclusion:
      Implicit methods that draw on the principles of SL can supplement the much-needed
      explicit instruction that helps children learn to read. This synergy of methods
      has the potential to spark innovative practices in literacy instruction and
      remediation provided by educators and clinicians to support typical learners and
      those with developmental disabilities.

PMID- 30120443
TI  - Statistical Learning and Spelling.
AB  - Purpose: The purpose of this article is to provide a tutorial on statistical
      learning and its role in learning to spell and to discuss the implications of the
      research for educators. Method: The tutorial begins with a discussion of
      statistical learning and its characteristics. It then discusses research on how
      statistical learning plays out in learning to spell, how spelling should be
      taught, and similarities and differences among learners. The focus is on the
      learning of English, although studies of other alphabetic writing systems are
      also considered. Research shows that, from an early age, children use their
      statistical learning skills to learn about the visual characteristics of written
      words. Children also use their statistical learning skills to help learn about
      the relations between visual units and units of language, supplementing what they
      are explicitly taught in school. Conclusion: Statistical learning plays an
      important role in learning to spell, and this can help to explain why some
      aspects of spelling are more difficult to learn than others. If children are to
      learn to spell effectively and efficiently, structured instruction is also
      important.

PMID- 30120445
TI  - Acquisition of Verb Meaning From Syntactic Distribution in Preschoolers With
      Autism Spectrum Disorder.
AB  - Purpose: Our goal was to investigate whether preschool children with autism
      spectrum disorder (ASD) can begin to learn new word meanings by attending to the
      linguistic contexts in which they occur, even in the absence of visual or social
      context. We focused on verbs because of their importance for subsequent language
      development. Method: Thirty-two children with ASD, ages 2;1-4;5 (years;months),
      participated in a verb-learning task. In a between-subjects design, they were
      randomly assigned to hear novel verbs in either transitive or intransitive
      syntactic frames while watching an unrelated silent animation or playing quietly
      with a toy. In an eye-tracking test, they viewed two video scenes, one depicting
      a causative event (e.g., boy spinning girl) and the other depicting synchronous
      events (e.g., boy and girl waving). They were prompted to find the referents of
      the novel verbs, and their eye gaze was measured. Results: Like typically
      developing children in prior work, children with ASD who had heard the verbs in
      transitive syntactic frames preferred to look to the causative scene as compared
      to children who had heard intransitive frames. Conclusions: This finding
      replicates and extends prior work on verb learning in children with ASD by
      demonstrating that they can attend to a novel verb's syntactic distribution
      absent relevant visual or social context, and they can use this information to
      assign the novel verb an appropriate meaning. We discuss points for future
      research, including examining individual differences that may impact success and
      contrasting social and nonsocial word-learning tasks directly.

PMID- 30120444
TI  - Distributional Cues to Language Learning in Children With Intellectual
      Disabilities.
AB  - Purpose: In typical development, distributional cues-patterns in input-are
      related to language acquisition processes. Statistical and implicit learning
      refer to the utilization of such cues. In children with intellectual disability,
      much less is known about the extent to which distributional cues are harnessed in
      mechanisms of language learning. Method: This tutorial presents what is known
      about the process of language learning in children with language impairments
      associated with different sources of intellectual disability: Williams syndrome,
      autism spectrum disorder, Down syndrome, and fragile X syndrome. Results: A broad
      view is taken on distributional cues relevant to language learning, including
      statistical learning (e.g., transitional probabilities) and other patterns that
      support lexical acquisition (e.g., sensitivities to sound patterns, cross
      situational word learning) or relate to syntactic development (e.g., nonadjacent
      dependencies). Conclusions: Critical gaps in the literature are highlighted.
      Research in this area is especially limited for Down syndrome and fragile X
      syndrome. Future directions for taking learning theories into account in
      interventions for children with intellectual disability are discussed, with a
      focus on the importance of language input.

PMID- 30120446
TI  - Effects of a Complexity-Based Approach on Generalization of Past Tense -ed and
      Related Morphemes.
AB  - Purpose: In a previous article, we reported that beginning treatment for regular
      past tense -ed with certain types of verbs led to greater generalization in
      children with developmental language disorder than beginning treatment with other
      types of verbs. This article provides updated data from that study, including the
      addition of data from 3 children, results from naturalistic language samples, and
      data from a third time point. Method: Twenty 4- to 9-year-old children with
      developmental language disorder (10 per condition) were randomly assigned to
      receive language intervention in which the verbs used to teach regular past tense
      -ed were manipulated. Half received easy first intervention, beginning with
      highly frequent, telic, phonologically simple verbs, and half received hard first
      intervention, beginning with less frequent, atelic, and phonologically complex
      verbs. The design used a train-to-criterion approach, with children receiving up
      to 36 visits. Performance was assessed using elicited production probes and
      language samples before intervention, immediately following intervention and 6-8
      weeks later. Results: Children in the hard first group showed greater gains on
      the use of regular past tense -ed in both structured probes (at immediate post
      only) and in language samples (at both immediate and delayed post). Gains
      attributable to therapy were not observed in untreated morphemes. Conclusions:
      This study suggests that the choice of therapy materials, with an eye on the role
      that treatment stimuli play in generalization, is important for treatment
      efficacy. Clinicians should consider early selection of atelic, lower-frequency,
      phonologically complex verbs when teaching children to use regular past tense 
      ed. Further work expanding this to other morphemes and a larger population is
      needed to confirm this finding.

PMID- 30120447
TI  - Individual and Developmental Differences in Distributional Learning.
AB  - Purpose: This study examined whether children and adults with developmental
      language disorder (DLD) could use distributional information in an artificial
      language to learn about grammatical category membership similarly to their
      typically developing (TD) peers and whether developmental differences existed
      within and between DLD and TD groups. Method: Sixteen children ages 7-9 with DLD,
      26 age-matched TD children, 17 college students with DLD, and 17 TD college
      students participated in this task. We used an artificial grammar learning
      paradigm in which participants had to use knowledge of category membership to
      determine the acceptability of test items that they had not heard during a
      training phase. Results: Individuals with DLD performed similarly to TD peers in
      distinguishing grammatical from ungrammatical combinations, with no differences
      between age groups. The order in which items were heard at test differentially
      affected child versus adult participants and showed a relation with attention and
      phonological working memory as well. Conclusion: Differences in ratings between
      grammatical and ungrammatical items in this task suggest that individuals with
      DLD can form grammatical categories from novel input and more broadly use
      distributional information. Differences in order effects suggest a developmental
      timeline for sensitivity to updating distributional information.

PMID- 30120450
TI  - Statistical Learning and Bilingualism.
AB  - Purpose: Over the last 2 decades, research on statistical learning has
      demonstrated its importance in supporting language development. Notably, most of
      the research to date has focused on monolingual populations (or has not reported
      the language background of participants). Several recent studies, however, have
      begun to focus on the impact of bilingualism on statistical learning. To date,
      the results have been quite mixed, with a handful of studies finding differences
      between monolinguals and bilinguals and several other studies reporting no
      differences. Thus, the purpose of this manuscript is to review the literature to
      date on how bilingualism impacts statistical learning abilities. Method: We
      review the contemporary literature, organized by the age of participants and by
      task when relevant. Conclusions: We note that there are many discrepant findings
      within this nascent field, although some trends have emerged. For instance,
      differences in performance may be attributed to factors such as age of
      acquisition. However, we note that the state of the field does not yet permit
      firm clinical recommendations.

PMID- 30120451
TI  - Take Home Points: How to Use Statistical Learning.
AB  - Purpose: The purpose of this epilogue is to synthesize the main points of the
      articles in this issue on statistical learning for clinicians. These points can
      be used to guide practice.

PMID- 30120453
TI  - Deck the Halls With Diverse Portraits.

PMID- 30120448
TI  - Learning Without Trying: The Clinical Relevance of Statistical Learning.
AB  - Purpose: Statistical learning research seeks to identify the means by which
      learners, with little perceived effort, acquire the complexities of language. In
      the past 50 years, numerous studies have uncovered powerful learning mechanisms
      that allow for learning within minutes of exposure to novel language input.
      Method: We consider the value of information from statistical learning studies
      that show potential for making treatment of language disorders faster and more
      effective. Results: Available studies include experimental research that
      demonstrates the conditions under which rapid learning is possible, research
      showing that these findings apply to individuals with disorders, and
      translational work that has applied learning principles in treatment and
      educational contexts. In addition, recent research on memory formation has
      implications for treatment of language deficits. Conclusion: The statistical
      learning literature offers principles for learning that can improve clinical
      outcomes for children with language impairment. There is potential for further
      applications of this basic research that is yet unexplored.

PMID- 30120449
TI  - The Role of Statistical Learning in Understanding and Treating Spoken Language
      Outcomes in Deaf Children With Cochlear Implants.
AB  - Purpose: Statistical learning-the ability to learn patterns in environmental
      input-is increasingly recognized as a foundational mechanism necessary for the
      successful acquisition of spoken language. Spoken language is a complex, serially
      presented signal that contains embedded statistical relations among linguistic
      units, such as phonemes, morphemes, and words, which represent the phonotactic
      and syntactic rules of language. In this review article, we first review recent
      work that demonstrates that, in typical language development, individuals who
      display better nonlinguistic statistical learning abilities also show better
      performance on different measures of language. We next review research findings
      that suggest that children who are deaf and use cochlear implants may have
      difficulties learning sequential input patterns, possibly due to auditory and/or
      linguistic deprivation early in development, and that the children who show
      better sequence learning abilities also display improved spoken language
      outcomes. Finally, we present recent findings suggesting that it may be possible
      to improve core statistical learning abilities with specialized training and
      interventions and that such improvements can potentially impact and facilitate
      the acquisition and processing of spoken language. Method: We conducted a
      literature search through various online databases including PsychINFO and
      PubMed, as well as including relevant review articles gleaned from the reference
      sections of other review articles used in this review. Search terms included
      various combinations of the following: sequential learning, sequence learning,
      statistical learning, sequence processing, procedural learning, procedural
      memory, implicit learning, language, computerized training, working memory
      training, statistical learning training, deaf, deafness, hearing impairment,
      hearing impaired, DHH, hard of hearing, cochlear implant(s), hearing aid(s), and
      auditory deprivation. To keep this review concise and clear, we limited inclusion
      to the foundational and most recent (2005-2018) relevant studies that explicitly
      included research or theoretical perspectives on statistical or sequential
      learning. We here summarize and synthesize the most recent and relevant
      literature to understanding and treating language delays in children using
      cochlear implants through the lens of statistical learning. Conclusions: We
      suggest that understanding how statistical learning contributes to spoken
      language development is important for understanding some of the difficulties that
      children who are deaf and use cochlear implants might face and argue that it may
      be beneficial to develop novel language interventions that focus specifically on
      improving core foundational statistical learning skills.

PMID- 30120454
TI  - Prosthetic Limbs Given Proprioception.

PMID- 30120455
TI  - New Nonprofit Biotech From Bill and Melinda Gates.

PMID- 30120456
TI  - Oral GLP-1 Analog for Type 2 Diabetes on the Horizon.

PMID- 30120457
TI  - Undisclosed Conflict of Interest.

PMID- 30120458
TI  - Typo in the Abstract.

PMID- 30120459
TI  - Colposcopy Rates Reported Incorrectly.

PMID- 30120460
TI  - Low-Dose Combination Blood Pressure Pharmacotherapy to Improve Treatment
      Effectiveness, Safety, and Efficiency.

PMID- 30120461
TI  - Traumatic Brain Injury and Risk of Suicide.

PMID- 30120464
TI  - Administrative Costs and Health Information Technology.

PMID- 30120462
TI  - Stop the Bleeding: Educating the Public.

PMID- 30120465
TI  - Foreign Letters: London.

PMID- 30120467
TI  - Variation in Deaths From Intentional Injury and Substance Use.

PMID- 30120466
TI  - BRCA1 and BRCA2 Testing in Medically Underserved Medicare Beneficiaries With
      Breast or Ovarian Cancer.

PMID- 30120468
TI  - Power of a Trial Investigating a Low-Intensity PSA-Based Screening Intervention.

PMID- 30120469
TI  - Neurological Symptoms in US Government Personnel in Cuba.

PMID- 30120470
TI  - Neurological Symptoms in US Government Personnel in Cuba.

PMID- 30120471
TI  - Neurological Symptoms in US Government Personnel in Cuba.

PMID- 30120472
TI  - Neurological Symptoms in US Government Personnel in Cuba.

PMID- 30120473
TI  - Power of a Trial Investigating a Low-Intensity PSA-Based Screening Intervention
      Reply.

PMID- 30120474
TI  - Variation in Deaths From Intentional Injury and Substance Use-Reply.

PMID- 30120475
TI  - Neurological Symptoms in US Government Personnel in Cuba-Reply.

PMID- 30120476
TI  - Effect of Cell-Free DNA Screening vs Direct Invasive Diagnosis on Miscarriage
      Rates in Women With Pregnancies at High Risk of Trisomy 21: A Randomized Clinical
      Trial.
AB  - Importance: Cell-free DNA (cfDNA) tests are increasingly being offered to women
      in the first trimester of pregnancies at a high risk of trisomy 21 to decrease
      the number of required invasive fetal karyotyping procedures and their associated
      miscarriages. The effect of this strategy has not been evaluated. Objective: To
      compare the rates of miscarriage following invasive procedures only in the case
      of positive cfDNA test results vs immediate invasive testing procedures
      (amniocentesis or chorionic villus sampling) in women with pregnancies at high
      risk of trisomy 21 as identified by first-trimester combined screening. Design,
      Setting, and Participants: Randomized clinical trial conducted from April 8,
      2014, to April 7, 2016, in 57 centers in France among 2111 women with pregnancies
      with a risk of trisomy 21 between 1 in 5 and 1 in 250 following combined first
      trimester screening. Interventions: Patients were randomized to receive either
      cfDNA testing followed by invasive testing procedures only when cfDNA tests
      results were positive (n = 1034) or to receive immediate invasive testing
      procedures (n = 1017). The cfDNA testing was performed using an in-house
      validated method based on next-generation sequencing. Main Outcomes and Measures:
      The primary outcome was number of miscarriages before 24 weeks' gestation.
      Secondary outcomes included cfDNA testing detection rate for trisomy 21. The
      primary outcome underwent 1-sided testing; secondary outcomes underwent 2-sided
      testing. Results: Among 2051 women who were randomized and analyzed (mean age,
      36.3 [SD, 5.0] years), 1997 (97.4%) completed the trial. The miscarriage rate was
      not significantly different between groups at 8 (0.8%) vs 8 (0.8%), for a risk
      difference of -0.03% (1-sided 95% CI, -0.68% to infinity; P = .47). The cfDNA
      detection rate for trisomy 21 was 100% (95% CI, 87.2%-100%). Conclusions and
      Relevance: Among women with pregnancies at high risk of trisomy 21, offering
      cfDNA screening, followed by invasive testing if cfDNA test results were
      positive, compared with invasive testing procedures alone, did not result in a
      significant reduction in miscarriage before 24 weeks. The study may have been
      underpowered to detect clinically important differences in miscarriage rates.
      Trial Registration: ClinicalTrials.gov Identifier: NCT02127515.

PMID- 30120477
TI  - Association Between Traumatic Brain Injury and Risk of Suicide.
AB  - Importance: Traumatic brain injuries (TBIs) can have serious long-term
      consequences, including psychiatric disorders. However, few studies have assessed
      the association between TBI and risk of suicide. Objective: To examine the
      association between TBI and subsequent suicide. Design, Setting, and
      Participants: Retrospective cohort study using nationwide registers covering 7
      418 391 individuals (>=10 years) living in Denmark (1980-2014) with 164 265 624
      person-years' follow-up; 567 823 (7.6%) had a medical contact for TBI. Data were
      analyzed using Poisson regression adjusted for relevant covariates, including
      fractures not involving the skull, psychiatric diagnoses, and deliberate self
      harm. Exposure: Medical contacts for TBI recorded in the National Patient
      Register (1977-2014) as mild TBI (concussion), skull fracture without documented
      TBI, and severe TBI (head injuries with evidence of structural brain injury).
      Main Outcomes and Measures: Suicide recorded in the Danish Cause of Death
      register until December 31, 2014. Results: Of 34 529 individuals who died by
      suicide (mean age, 52 years [SD, 18 years]; 32.7% women; absolute rate 21 per 100
      000 person-years [95% CI, 20.8-21.2]), 3536 (10.2%) had medical contact: 2701
      with mild TBI, 174 with skull fracture without documented TBI, and 661 with
      severe TBI. The absolute suicide rate was 41 per 100 000 person-years (95% CI,
      39.2-41.9) among those with TBI vs 20 per 100 000 person-years (95% CI, 19.7
      20.1) among those with no diagnosis of TBI. The adjusted incidence rate ratio
      (IRR) was 1.90 (95% CI, 1.83-1.97). Compared with those without TBI, severe TBI
      (absolute rate, 50.8 per 100 000 person-years; 95% CI, 46.9-54.6) was associated
      with an IRR of 2.38 (95% CI, 2.20-2.58), whereas mild TBI (absolute rate, 38.6
      per 100 000 person-years; 95% CI, 37.1-40.0), and skull fracture without
      documented TBI (absolute rate, 42.4 per 100 000 person-years; 95% CI, 36.1-48.7)
      had an IRR of 1.81 (95% CI, 1.74-1.88) and an IRR of 2.01 (95% CI, 1.73-2.34),
      respectively. Suicide risk was associated with number of medical contacts for TBI
      compared with those with no TBI contacts: 1 TBI contact, absolute rate, 34.3 per
      100 000 person-years (95% CI, 33.0-35.7; IRR, 1.75; 95% CI, 1.68-1.83); 2 TBI
      contacts, absolute rate, 59.8 per 100 000 person-years (95% CI, 55.1-64.6; IRR,
      2.31; 95% CI, 2.13-2.51); and 3 or more TBI contacts, absolute rate, 90.6 per 100
      000 person-years (95% CI, 82.3-98.9; IRR, 2.59; 95% CI, 2.35-2.85; all P < .001
      for the IRR's). Compared with the general population, temporal proximity since
      the last medical contact for TBI was associated with risk of suicide (P<.001),
      with an IRR of 3.67 (95% CI, 3.33-4.04) within the first 6 months and an
      incidence IRR of 1.76 (95% CI, 1.67-1.86) after 7 years. Conclusions and
      Relevance: In this nationwide registry-based retrospective cohort study
      individuals with medical contact for TBI, compared with the general population
      without TBI, had increased suicide risk.

PMID- 30120479
TI  - Scabies.

PMID- 30120481
TI  - A Refugee's Journey: Told in 55-Word Stories.

PMID- 30120483
TI  - Few Americans Hit Fitness Targets.

PMID- 30120484
TI  - Fatal Sepsis Linked to Platelets.

PMID- 30120478
TI  - Fixed Low-Dose Triple Combination Antihypertensive Medication vs Usual Care for
      Blood Pressure Control in Patients With Mild to Moderate Hypertension in Sri
      Lanka: A Randomized Clinical Trial.
AB  - Importance: Poorly controlled hypertension is a leading global public health
      problem requiring new treatment strategies. Objective: To assess whether a low
      dose triple combination antihypertensive medication would achieve better blood
      pressure (BP) control vs usual care. Design, Setting, and Participants:
      Randomized, open-label trial of a low-dose triple BP therapy vs usual care for
      adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg;
      or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm
      Hg) requiring initiation (untreated patients) or escalation (patients receiving
      monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban
      hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in
      October 2017. Interventions: A once-daily fixed-dose triple combination pill (20
      mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy
      (n = 349) or usual care (n = 351). Main Outcomes and Measures: The primary
      outcome was the proportion achieving target systolic/diastolic BP (<140/90 mm Hg
      or <130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6
      months. Secondary outcomes included mean systolic/diastolic BP difference during
      follow-up and withdrawal of BP medications due to an adverse event. Results:
      Among 700 randomized patients (mean age, 56 years; 58% women; 29% had diabetes;
      mean baseline systolic/diastolic BP, 154/90 mm Hg), 675 (96%) completed the
      trial. The triple combination pill increased the proportion achieving target BP
      vs usual care at 6 months (70% vs 55%, respectively; risk difference, 12.7% [95%
      CI, 3.2% to 22.0%]; P < .001). Mean systolic/diastolic BP at 6 months was 125/76
      mm Hg for the triple combination pill vs 134/81 mm Hg for usual care (adjusted
      difference in postrandomization BP over the entire follow-up: systolic BP, -9.8
      [95% CI, -7.9 to -11.6] mm Hg; diastolic BP, -5.0 [95% CI, -3.9 to -6.1] mm Hg; P
      < .001 for both comparisons). Overall, 419 adverse events were reported in 255
      patients (38.1% for triple combination pill vs 34.8% for usual care) with the
      most common being musculoskeletal pain (6.0% and 8.0%, respectively) and
      dizziness, presyncope, or syncope (5.2% and 2.8%). There were no significant
      between-group differences in the proportion of patient withdrawal from BP
      lowering therapy due to adverse events (6.6% for triple combination pill vs 6.8%
      for usual care). Conclusions and Relevance: Among patients with mild to moderate
      hypertension, treatment with a pill containing low doses of 3 antihypertensive
      drugs led to an increased proportion of patients achieving their target BP goal
      vs usual care. Use of such medication as initial therapy or to replace
      monotherapy may be an effective way to improve BP control. Trial Registration:
      anzctr.org.au Identifier: ACTRN12612001120864; slctr.lk Identifier:
      SLCTR/2015/020.

PMID- 30120485
TI  - Global Variations and Challenges With Tubercular Uveitis in the Collaborative
      Ocular Tuberculosis Study.
AB  - Purpose: The aim of this study was to examine regional variation management
      practices and outcomes for tubercular uveitis (TBU). Methods: In this
      retrospective multinational cohort study, patients from 25 international eye care
      centers diagnosed with TBU with a minimum follow-up of 1 year were included. The
      geographic variation in treatment outcomes on survival analysis in patients with
      TBU were analyzed. Treatment failure is defined as a persistence or recurrence of
      inflammation within 6 months of completing antitubercular therapy, the inability
      to taper oral corticosteroids to less than 10 mg/d or topical corticosteroid
      drops to less than 2 drops daily, and/or recalcitrant inflammation necessitating
      corticosteroid-sparing immunosuppressive therapy. Results: Records of 945
      patients (1485 eyes) with TBU were analyzed. The mean age was 41.3 +/- 15.0 years
      (range, 4-90 years), with more males (52.9%, n = 500/945) and predominant Asian
      ethnicity (74.4%, n = 690/927). Most patients had no symptoms (92.0%, n =
      655/712) or history (76.7%, n = 604/787) suggestive of pulmonary tuberculosis
      (TB). Some patients had evidence of inactive pulmonary TB on chest X-rays (26.9%,
      n = 189/702) or chest computed tomography (68.6%, n = 109/159). Patients with
      western geographic origin (log-rank = 6.47, P = 0.010), African or Hispanic
      ethnicity (log-rank = 19.9, P < 0.001), and positive immigrant status (log-rank =
      4.89, P = 0.027) had poorer survival outcomes. Conclusions: This is a first-ever
      multinational analysis of TBU that highlights regional differences in treatment
      outcomes for this elusive form of extrapulmonary TB. Our findings will help in
      the design of future collaborative studies together with internists to develop
      best practice guidelines for this early opportunity to address TB infection and
      strategies to target at-risk groups such as immigrants.

PMID- 30120486
TI  - The Impact of Choroidal Swelling on Optic Nerve Head Deformation.
AB  - Purpose: Choroid geometry and swelling have been proposed to contribute to ocular
      pathologies. Thus, it is important to understand how the choroid may impact the
      optic nerve head (ONH) biomechanical environment. We developed a finite element
      model to study how acute choroidal swelling and choroid geometry affect ONH
      deformation. Methods: We developed two geometric models of the ONH: one with a
      "blunt" choroidal insertion and another with a "tapered" choroid insertion. We
      examined how choroidal volume changes (2.1-14.2 MUL, estimated to occur during
      the ocular pulse) impact biomechanical strain in three tissue regions: the
      prelaminar neural tissue, lamina cribrosa, and retrolaminar neural tissue. Then,
      we performed a sensitivity analysis to understand how variation in ONH pressures,
      tissue material properties, and choroidal swelling influenced the peak tissue
      strains. Results: Choroidal swelling in the blunt choroid geometry had a large
      impact on the strains in the prelaminar neural tissue, with magnitudes comparable
      to those expected to occur due to an IOP of 30 mm Hg. Choroidal swelling in the
      tapered choroid geometry also affected strains but to a lesser extent compared to
      the blunt geometry. A sensitivity analysis confirmed that choroidal swelling was
      more influential on prelaminar neural tissue strains in the blunt choroid
      geometry. Conclusions: Choroid anatomy and swelling can interact to play an
      important role in prelaminar neural tissue deformation. These findings suggest
      that the choroid may play an important, and previously unappreciated, role in ONH
      biomechanics, and motivate additional research to better define the in vivo
      effects of choroidal volume change.

PMID- 30120489
TI  - Replica to the Opinion Letter regarding the article "Sensitization of colorectal
      cancer cells to irinotecan by the Survivin inhibitor LLP3 depends on XAF1
      proficiency in the context of mutated p53" (Arch Toxicol
      https://doi.org/10.1007/s00204-018-240-x).

PMID- 30120487
TI  - [Transition from neuropediatrics to neurology in neuromuscular diseases].
AB  - BACKGROUND: Neuromuscular diseases in childhood, adolescence and adulthood are
      rare or very rare diseases and for many of them the prevalence and incidence are
      unknown. Causal therapies are currently used for individual disease entities
      only. Nevertheless, new genetic methods, a better understanding of the
      pathophysiology and multidisciplinary treatment concepts help to improve patient
      life expectancy and quality of life. As a result, more and more patients with an
      early disease onset reach adulthood and further care in adult medicine is
      necessary. This imposes new challenges particularly on neurology and the
      requirements for interdisciplinary cooperation in adult medicine are increased.
      OBJECTIVE: How can transition be made meaningful? Where do structural and content
      problems stand out? MATERIAL AND METHOD: Using the example of Duchenne muscular
      dystrophy, the content and structural requirements for transition are presented
      and important aspects and possible problems are pointed out. CONCLUSION: The
      transition process is complex and requires time and personnel resources. If
      carried out sensibly, it can lead to a better and more efficient care of patients
      in the long term and thus can also become economically more effective.

PMID- 30120488
TI  - [Tauopathies : From molecule to therapy].
AB  - BACKGROUND: The microtubule-associated tau protein is the defining denominator of
      a group of neurodegenerative diseases termed tauopathies. OBJECTIVE: Provide a
      timely state of the art review on recent scientific advances in the field of
      tauopathies. MATERIAL AND METHODS: Systematic review of the literature from the
      past 10 years. RESULTS: Tau proteins are increasingly being recognized as a
      highly variable protein, underlying and defining a spectrum of molecularly
      defined diseases, with a clinical spectrum ranging from dementia to hypokinetic
      movement disorders. Genetic variation at the tau locus can trigger disease or
      modify disease risk. Tau protein alterations can damage nerve cells and propagate
      pathologies through the brain. Thus, tau proteins may serve both as a serological
      and imaging biomarker. Tau proteins also provide a broad spectrum of rational
      therapeutic interventions to prevent disease progression. This knowledge has led
      to modern clinical trials. CONCLUSION: The field of tauopathies is in a state of
      dynamic and rapid progress, requiring close interdisciplinary collaboration.

PMID- 30120490
TI  - Dual lumen balloon spontaneous inflation during embolization.

PMID- 30120491
TI  - Do intoxicated witnesses produce poor facial composite images?
AB  - RATIONALE: The effect of alcohol intoxication on witness memory and performance
      has been the subject of research for some time, however, whether intoxication
      affects facial composite construction has not been investigated. OBJECTIVES:
      Intoxication was predicted to adversely affect facial composite construction.
      METHODS: Thirty-two participants were allocated to one of four beverage
      conditions consisting of factorial combinations of alcohol or placebo at face
      encoding, and later construction. Participants viewed a video of a target person
      and constructed a composite of this target the following day. The resulting
      images were presented as a full face composite, or a part face consisting of
      either internal or external facial features to a second sample of participants
      who provided likeness ratings as a measure of facial composite quality. RESULTS:
      Intoxication at face encoding had a detrimental impact on the quality of facial
      composites produced the following day, suggesting that alcohol impaired the
      encoding of the target faces. The common finding that external compared to
      internal features are more accurately represented was demonstrated, even
      following alcohol at encoding. This finding was moderated by alcohol and target
      face gender such that alcohol at face encoding resulted in reduced likeness of
      external features for male composite faces only. CONCLUSIONS: Moderate alcohol
      intoxication impairs the quality of facial composites, adding to existing
      literature demonstrating little effect of alcohol on line-up studies. The impact
      of intoxication on face perception mechanisms, and the apparent narrowing of
      processing to external face areas such as hair, is discussed in the context of
      alcohol myopia theory.

PMID- 30120493
TI  - ?

PMID- 30120492
TI  - [Trichophyton mentagrophytes-from snow leopard to man : A molecular approach for
      uncovering the chain of infection].
AB  - Sources of infection for Trichophyton (T.) mentagrophytes-a zoophilic
      dermatophyte-comprise pet rodents (guinea pigs, mice, rabbits) and sometimes
      cats. Human infections due to dermatophytes after contact with zoo animals,
      however, are extreme rare. Four zoo keepers from Basel Zoo were diagnosed to
      suffer from tinea manus and tinea corporis due to T. mentagrophytes. The 22-year
      old daughter of one zoo keeper was also infected with tinea corporis after having
      worked in the snow leopard section for one day. The strain of the index patient
      was confirmed by a direct uniplex-PCR-EIA and sequence analysis of the ribosomal
      internal transcribed spacer (ITS) region (18S rRNA, ITS1, 5.8S rRNA, ITS2, 28S
      rRNA) as T. mentagrophytes. Three young snow leopards from Basel Zoo were
      identified as the origin of the fungal skin infection. The transmission occurred
      due to direct contact of the zoo keepers with the young snow leopards when
      removing hedgehog ticks (Ixodes hexagonus). Two adult snow leopards had developed
      focal alopecia of the facial region which was diagnosed as dermatomycoses due to
      T. mentagrophytes by the zoo veterinarians. By sequence analysis, both the
      strains from the animals and a single strain of the index patient showed 100%
      accordance proving transmission of T. mentagrophytes from animals to the zoo
      keepers. Molecular biological identification revealed a strong relationship to a
      strain of T. mentagrophytes from European mink (Mustela lutreola) from Finland.
      Treatment of patients was started using topical ointment with azole antifungals,
      and oral terbinafine 250 mg once daily for 4 weeks. Both adult snow leopards and
      the asymptomatic young animals were treated with oral itraconazole.

PMID- 30120494
TI  - Feasibility of mapping breast cancer with supine breast MRI in patients scheduled
      for oncoplastic surgery.
AB  - OBJECTIVES: To prospectively determine the feasibility of preoperative supine
      breast MRI in breast cancer patients scheduled for oncoplastic breast-conserving
      surgery. METHODS: In addition to a diagnostic prone breast MRI, a supplementary
      supine MRI was performed with the patient in the surgical position including skin
      markers. Tumours' locations were ink-marked on the skin according to findings
      obtained from supine MRI. Changes in tumours' largest diameter and locations
      between prone and supine MRI were measured and compared to histology. Nipple-to
      tumour and tumour-to-chest wall distances were also measured. Tumours and
      suspicious areas were surgically removed according to skin ink-markings. The
      differences between MRI measurements with reference to histopathology were
      evaluated with the paired-sample t test. RESULTS: Fourteen consecutive patients,
      15 breasts and 27 lesions were analysed. Compared to histology, prone MRI
      overestimated tumour size by 47.1% (p = 0.01) and supine MRI by 14.5% (p =
      0.259). In supine MRI, lesions' mean diameters and areas were smaller compared to
      prone MRI (- 20.9%, p = 0.009 and - 38.3%, p = 0.016, respectively). This
      difference in diameter was more pronounced in non-mass lesions (- 31.2%, p =
      0.031) compared to mass lesions (- 9.2%, p = 0.009). Tumours' mean distance from
      chest wall diminished by 69.4% (p < 0.001) and from nipple by 18.2% (p < 0.001).
      Free microscopic margins were achieved in first operation in all patients.
      CONCLUSIONS: Supine MRI in the surgical position is feasible and useful in the
      precise localisation of prone MRI-detected lesions and provides a helpful tool to
      implement in surgery. Supine MRI more accurately determines tumours' size and
      location and might have an important role to diminish overestimations. KEY
      POINTS: * Breath-hold supine breast MRI is feasible using commercially available
      coils and sequences. * Size and area of lesions on MRI were consistently smaller
      when measured from the supine position as compared to the prone position. *
      Supine breast MRI is useful in the precise preoperative localisation of prone MRI
      detected lesions. *.

PMID- 30120495
TI  - [Intestinal cross-talk : The gut as motor of multiple organ failure].
AB  - The central role of the organ system "gut" for critically ill patients has not
      been acknowledged until the last decade. The gut is a crucial immunologic,
      metabolic and neurologic organ system and impairment of its functions is
      associated with morbidity and mortality. The gut has a central position in the
      cross-talk between organs and dysfunction of the gut may result in impairment of
      other intra-abdominal and extra-abdominal organ systems. The intestinal tract is
      the most important source of endogenous infections and determines the
      inflammatory status of the organism. Gut failure is an element of the multiple
      organ dysfunction syndrome (MODS). The leading mechanism in the evolution of
      endogenous infections is the intestinal translocation of microbes. A dysbiosis
      and damage of the intestinal mucosa leads to a disorder of the mucosal barrier
      function, increases the permeability and promotes translocation (leaky gut
      hypothesis). A further crucial mechanism of organ interactions is the increase in
      intra-abdominal pressure. Intra-abdominal hypertension promotes further injury of
      the gut, increases translocation and inflammation and causes dysfunction of other
      organ systems, such as the kidneys, the cardiovascular system and the lungs.
      Maintaining and/or restoring intestinal functions must be a priority of any
      intensive care therapy. The most important measure is early enteral nutrition.
      Other measures are the preservation of motility and modulation of the intestinal
      microbiome. Intra-abdominal hypertension must be reduced by an individually
      adapted infusion therapy, positioning of the patient, administration of drugs
      (abdominal compliance) and decompression (by tubes, endoscopically or in severe
      cases surgically).

PMID- 30120496
TI  - Age-corrected hearing loss after chemoradiation in cervical cancer patients.
AB  - OBJECTIVE: This study aimed to evaluate subjective and objective hearing loss in
      cervical cancer patients after chemoradiation with cisplatin (mono). PATIENTS AND
      METHODS: A total of 51 cervical cancer patients with indication for
      chemoradiation were included. Pure tone and impedance audiometry were performed
      before and after chemoradiation. Hearing loss was scaled according to ASHA
      criteria. Subjective hearing was assessed with the Oldenburger Sentence Test. To
      consider age-dependent changes, hearing loss was corrected for age and the time
      interval between measurements. RESULTS: Median age at diagnosis was 46 years, 46%
      were active/former smokers (n = 24), 28 (54%) patients were never-smokers. Median
      total weekly cisplatin dose was 70 +/- 14.2 mg. Cumulative doses of cisplatin
      during chemoradiation ranged between 115.2 and 400 mg cisplatin (mean 336.1 mg,
      median 342 +/- 52.7 mg). The median interval between last chemotherapy and second
      audiometry was 320 +/- 538 days (35-2262 days). Changes in hearing threshold >=20
      dB were experienced by 32/52 patients (62%) following chemoradiation, 55% of them
      for frequencies >=6000 Hz. No statistically significant hearing loss remained
      after chemoradiation upon correction for age and time interval. Patients >40
      years had a higher risk of hearing loss than younger patients. Objective data on
      hearing function did not correlate with subjective hearing loss and did not
      impair daily activity in any patient. CONCLUSION: Chemoradiation with cumulative
      cisplatin doses up to 400 mg did not lead to significant impairment of objective
      or subjective hearing. For cervical cancer patients undergoing chemoradiation,
      standard audiometry is not indicated.

PMID- 30120497
TI  - Enhancing research for undergraduates through a nanotechnology training program
      that utilizes analytical and bioanalytical tools.
AB  - Nanotechnology is a broad field combining traditional scientific disciplines;
      however, analytical chemistry plays an important role in material design,
      synthesis, characterization, and application. This article emphasizes the
      uniqueness of nanotechnology and the importance of providing high-quality
      undergraduate research experiences to both attract and retain talented
      individuals to the field of nanotechnology. In response to this need to develop a
      strong and sustainable nanotechnology work force, strategies to create authentic
      research experiences are considered within the framework of an interdisciplinary
      nanotechnology environment at West Virginia University. The program, named
      NanoSAFE Research Experiences for Undergraduates (REU), embeds students in
      different departments at West Virginia University and in research laboratories
      within the National Institute of Occupational Safety and Health. A large number
      of participants have little or no prior research experience and a strong effort
      is made to recruit applicants from under-represented populations. Components
      designed to foster research proficiency include frequent reporting, a strong peer
      network, and training for secondary mentors. Evidence, which includes student
      publications and assessment findings demonstrating self-efficacy, is discussed to
      substantiate the viability of the strategies used in the 2016-2018 program.
      Graphical abstract ?.

PMID- 30120498
TI  - More vection means more velocity storage activity: a factor in visually induced
      motion sickness?
AB  - Full-field visual rotation around the vertical axis induces a sense of self
      motion (vection), optokinetic nystagmus (OKN), and, eventually, also motion
      sickness (MS). If the lights are then suddenly switched off, optokinetic
      afternystagmus (OKAN) occurs. This is due to the discharge of the velocity
      storage mechanism (VSM), a central integrative network that has been suggested to
      be involved in motion sickness. We previously showed that visually induced motion
      sickness (VIMS) following optokinetic stimulation is dependent on vection
      intensity. To shed light on this relationship, the current study investigated
      whether vection intensity is related to VSM activity, and thus, to the OKAN. In
      repetitive trials (eight per condition), 15 stationary participants were exposed
      to 120 s of visual yaw rotation (60 degrees /s), followed by 90 s in darkness.
      The visual stimulus either induced strong vection (i.e., scene rotating normally)
      or weak vection (central and peripheral part moving in opposite directions). Eye
      movements and subjective vection intensity were continuously measured. Results
      showed that OKAN occurred less frequently and with lower initial magnitude in the
      weak-vection condition compared to the strong-vection condition. OKAN decay time
      constants were not significantly different. The results suggest that the stimuli
      that produced strong vection also enhanced the charging of the VSM. As VSM
      activity presumably is a factor in motion sickness, the enhanced VSM activity in
      our strong-vection condition hints at an involvement of the VSM in VIMS, and
      could explain why visual stimuli producing a strong sense of vection also elicit
      high levels of VIMS.

PMID- 30120499
TI  - People-Centered and Ecosystem-Based Knowledge Co-Production to Promote Proactive
      Biodiversity Conservation and Sustainable Development in Namibia.
AB  - Growing levels of uncertainty and vulnerability generated by land use conversion
      and climate change set demands on local communities and national institutions to
      build synergies between the diverse array of knowledge systems in order to
      provide policy makers and practitioners with the best available information to
      decide what urgent actions must be taken. Science policy arenas and agreements
      such as the Intergovernmental Platform on Biodiversity and Ecosystem Services
      (IPBES) and the Convention on Biological Diversity (CBD) recognize the importance
      of different types of knowledge and the need for broad stakeholder involvement,
      yet the use of indigenous and local knowledge (ILK) in environmental decision
      making processes is still underdeveloped. This study involved working with local
      stakeholders, using the MARISCO method (adaptive MAnagement of vulnerability and
      RISks at COnservation sites) to carry out a systematic situation analysis of the
      existing socioenvironmental conditions. The assessments were conducted in the
      Kavango East Region in northern Namibia with the participation of inhabitants of
      the Khaudum North Complex, a protected area network covering wooded savannahs
      belonging to the Northern Kalahari sandveld. General outcomes of the assessments
      and evaluations made by the local stakeholders concerning the most critical
      drivers of degradation of the ecosystems appeared to support existing scientific
      knowledge of the study area, demonstrating that community-based assessments can
      provide valuable information about socioecological systems where scientific data
      are scarce. The findings of this study also highlight the importance of power
      dynamics for the implementation of participatory processes and the interpretation
      of their outcomes.

PMID- 30120500
TI  - Comparison of suctioning and traditional ureteral access sheath during flexible
      ureteroscopy in the treatment of renal stones.
AB  - PURPOSE: To compare the efficiency and safety of suctioning ureteral access
      sheath (UAS) and traditional UAS during flexible ureteroscopy (FURS) for
      treatment of renal stones. METHODS: Between January 2015 and December 2017, 165
      patients who had renal stones successfully underwent FURS with suctioning UAS
      created by connecting a channel on the tail of the suctioning UAS to a vacuum
      device. The outcomes of these patients were compared with those of 165 patients
      undergoing FURS with traditional UAS using a 1:1 scenario matched-pair analysis.
      The matching parameters were age, gender and stone burden. RESULTS: The baseline
      characteristics were homogeneous between the two groups. The suctioning UAS group
      had significantly higher SFR one day postoperatively (82.4% vs. 71.5%; P = 0.02),
      but SFR 1 month postoperatively was comparable in the two groups (P = 0.13). The
      incidence of overall complications was significantly higher in the traditional
      UAS group (24.8% vs 11.5%; P < 0.001). Regarding individual complications, the
      traditional UAS group was associated with a significantly higher incidence of
      fever (13.9% vs 5.5%; P = 0.009) and urosepsis requiring only additional
      antibiotics (6.7% vs 1.8%; P = 0.029). No significant difference was noted in the
      incidence of septic shock, hematuria, steinstrasse or ureteral stricture. The
      suctioning UAS group had significantly shorter operative time (49.7 + 16.3 min
      vs. 57.0 +/- 14.0 min; P < 0.001). CONCLUSIONS: Compared to traditional UAS
      during FURS for treating renal stones, suctioning UAS had the advantages of
      higher SFR 1 day postoperatively, a lower incidence of infectious complications
      and a shorter operative time. Further well-designed studies are required to
      confirm the results.

PMID- 30120501
TI  - Comparative sensitivity and specificity of imaging modalities in staging bladder
      cancer prior to radical cystectomy: a systematic review and meta-analysis.
AB  - PURPOSE: The detection of lymph node metastases in bladder cancer has a
      significant impact on treatment decisions. Multiple imaging modalities are
      available to clinicians including magnetic resonance imaging, computed tomography
      and positron emission tomography. We aimed to investigate the utility of
      alternate imaging modalities on pre-cystectomy imaging in bladder cancer for the
      detection of lymph node metastases. METHODS: We performed systematic search of
      Web of Science (including MEDLINE), EMBASE and Cochrane libraries in accordance
      with the PRISMA statement. Studies comparing lymph node imaging findings with
      final histopathology were included in our analysis. Sensitivity and specificity
      data were quantified using patient-based analysis. A true positive was defined as
      a node-positive patient on imaging and node positive on histopathology. Meta
      analysis of studies was performed using a mixed-effects, hierarchical logistic
      regression model. RESULTS: Our systematic search identified 35 articles suitable
      for inclusion. MRI and PET have a higher sensitivity than CT while the
      specificity of all modalities was similar. The summary MRI sensitivity = 0.60
      (95% CI 0.44-0.74) and specificity = 0.91 (95% CI 0.82-0.96). Summary PET/CT
      sensitivity = 0.56 (95% CI 0.49-0.63) and specificity = 0.92 (95% CI 0.86-0.95).
      Summary CT sensitivity = 0.40 (95% CI 0.33-0.49) and specificity = 0.92 (95% CI
      0.86-0.95). CONCLUSION: MRI and PET/CT provides superior sensitivity compared to
      CT for detection of positive lymph nodes in bladder cancer prior to cystectomy.
      There is variability in the accuracy that current imaging modalities achieve
      across different studies. A number of other factors impact on detection accuracy
      and these must be considered.

PMID- 30120502
TI  - Differential diagnosis of posterior fossa tumours in children: new insights.
AB  - Central nervous system neoplasms are the most common solid tumours that develop
      in children, with the greatest proportion located in the infratentorium. The 2016
      World Health Organization Central Nervous System tumour classification evolved
      from the 2007 edition with the integration of molecular and genetic profiling
      into the diagnosis, the addition of new entities and the removal of others.
      Radiology can assist with the subtyping of tumours from certain characteristics
      described below to provide prognostic information and guide further management.
      The latest insights into the radiologic characteristics of these posterior fossa
      tumours are presented below: medulloblastoma, ependymoma, pilocytic astrocytoma,
      embryonal tumours with multilayered rosettes, atypical teratoid rhabdoid tumours,
      diffuse midline glioma and the new entity of diffuse leptomeningeal glioneuronal
      tumours.

PMID- 30120503
TI  - Regulatory mechanisms of PD-L1 expression in cancer cells.
AB  - Immunotherapy targeting the PD-L1/PD-1 pathway using antibodies is effective in
      the clinical treatment of a multitude of cancers. This makes research of the
      regulatory mechanisms of PD-1 expression in cancer cells intriguing. PD-L1
      expression can be categorized into inducible expression, attributed to extrinsic
      factors in the microenvironment, and constitutive expression, attributed to
      intrinsic cancer-driving gene alteration. The mechanisms of PD-L1 expression in
      cancer cells operate at multiple levels, including gene amplification, chromatin
      modification, transcription, posttranscription, translation and posttranslation.
      Moreover, some open questions in this field that need to be answered in future
      research are proposed. Studies of regulatory mechanisms of PD-L1 expression pave
      the way for the application of more effective approaches in the future of cancer
      immunotherapy.

PMID- 30120504
TI  - Pb Adsorption on Soil Typical to an Ammunition Destruction Site.
AB  - Pb, one of the constituents of ammunition, was identified as a contaminant in an
      ammunition destruction site. The present study aimed to assess Pb adsorption in
      the horizons of an uncontaminated representative soil profile of the region where
      the ammunition destruction site is located. Batch test experiments were performed
      to determine Pb adsorption in soil horizons, using solutions with natural and
      modified pH. The ISOFIT software was used to select the isotherm model that best
      fit Pb adsorption in soil horizons. The results showed that the Langmuir model is
      the best fit, because it presented the lowest corrected Akaike information
      criterion value. In addition, the graphical analysis indicated a Langmuir-type
      isotherm. The Langmuir isotherm parameter (Q0) indicated lower Pb adsorption
      capacity in the surface soil layers when compared with that in the deeper layers.
      The change in the initial solution pH influenced Pb adsorption, mainly in
      superficial horizons. Thus, the risk of soil Pb contamination might be more
      pronounced in the surface soil layers.

PMID- 30120505
TI  - Analysis and Occurrence of Bisphenol A in Mediterranean Mussels (Mytilus
      galloprovincialis) Sampled from the Slovenian Coastal Waters of the North
      Adriatic Sea.
AB  - During 2015, a selection of Mediterranean mussels (Mytilus galloprovincialis) and
      seawater were sampled along the Slovenian coast, which is part of the North
      Adriatic Sea, in order to test for the presence of bisphenol A (BPA). The
      concentration of the BPA in the tissues of mussels sampled from the farms and
      open sea was from < 0.03 to 0.55 ug kg-1 of w.w. and from < 0.03 to 0.46 ug kg-1
      of w.w., respectively. The mussel shells from the farms and open sea contained
      from 0.01 to 0.3 ug BPA kg-1 of w.w. and from 0.04 to 0.27 ug BPA kg-1 of w.w.,
      respectively. In a harbour, mussel tissue and shell concentration of BPA was 0.21
      and 0.18 ug BPA kg-1 of w.w., respectively. The seawater in the shellfish farms
      and the open sea was contaminated with an average of 0.007 ug l-1 of BPA.

PMID- 30120506
TI  - Herbicide Toxicity to Soybean-Rhizobium Symbiosis as Affected by Soil pH.
AB  - The current study examined whether soil pH could influence the toxicity of
      herbicides to soybean-rhizobium symbiosis. This can be useful for farmers to
      minimize the toxicity of them to crop-rhizobium symbiosis via applying their
      reduced doses. The toxicity of bentazon, metribuzin, and trifluralin to soybean
      rhizobium symbiosis was investigated in pH 6.4, 7.2, and 8 soils. Seed
      inoculation decreased shoot:root (S:R) ratio but increased height, shoot dry
      weight (SDW), root dry weight (RDW), shoot nitrogen content (SNC), root nitrogen
      content (RNC), and nitrogen fixation effectiveness (NFE) in the pH 7.2 soil
      without herbicide application. All herbicides decreased NFE in all soil pH
      regimes except metribuzin in the pH 6.4 soil. Unlike trifluralin, the toxicity of
      bentazon and metribuzin to soybean-rhizobium symbiosis was influenced by the soil
      pH. It can be concluded that soil acidification and alkalization, which can
      rapidly occur in agroecosystems, can decrease and increase the toxicity of
      bentazon and metribuzin to soybean-rhizobium symbiosis, respectively.

PMID- 30120507
TI  - Location of the course of the mandibular canal, anterior loop and accessory
      mental foramen through cone-beam computed tomography.
AB  - PURPOSE: This study aimed at identifying the course of the mandibular canal, the
      presence of anterior loop and accessory mental foramen, as well as verifying the
      association between these variables through the analysis of cone beam computed
      tomography (CBCT) exams. METHODS: CBCT images were analyzed to identify the type
      of mandibular canal path, classified into three types: (I) catenary; (II)
      progressive descending; and (III) straight. In addition, the presence of anterior
      loop and accessory mental foramen was analyzed. The variables were summarized by
      measures of absolute frequency, relative, mean and standard deviation. The Chi
      square and Fisher's exact tests were used in the comparative analysis of the
      frequency distribution. The level of significance was 5%. RESULTS: The most
      frequent mandibular canal course was straight type (74.4%), followed by catenary
      (19.4%) and finally the progressive descending (6.2%). It was observed a
      prevalence of 10.2% for anterior loop and 7.9% for accessory mental foramen.
      There was no association between the presence of anterior loop (P = 0.798) and
      accessory mental foramen (P 0.480) with the mandibular canal course pattern, as
      well as no association between the anterior loop and the presence of the
      accessory mental foramen (P = 0.407). CONCLUSIONS: The CBCT analysis is the best
      methodology for the investigation and localization of mandibular anatomical
      variations, which provides a good image quality of the bone tissue and details of
      the anatomical structures, reducing the risk of injury to the lower alveolar
      vascular-nervous bundle and, consequently, cause paralysis and hemorrhage in the
      anterior region of the mandible and adjacent structures.

PMID- 30120509
TI  - [Meeting of the Working Group on the History of Pathology : 102nd Annual Congress
      of the German Society of Pathology].

PMID- 30120510
TI  - [Meeting of the Working Group on Cytopathology of the German Society of
      Pathology, 2018].

PMID- 30120508
TI  - Efficacy of commonly prescribed analgesics in the management of osteoarthritis: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: Pain management is a cornerstone of osteoarthritis (OA) management.
      The aim of this review is to obtain current, literature-based estimates of the
      effect of common pharmacologic treatments on pain reduction in OA. METHODS: A
      MEDLINE search (2006-2016) was conducted for randomized controlled trials
      studying acetaminophen, oral NSAIDs, topical NSAIDs, COX-2 inhibitors, and
      opioids in the treatment of OA pain. Drug effect on pain was estimated using
      relative change in pain, and expressed as percentage change. An overall effect
      for each drug category was obtained as a weighted average of study-specific
      effects, with weights based on each study's sample size. RESULTS: Twenty-nine
      studies were included. The effect on pain was estimated in a total of 43
      treatment arms (acetaminophen n = 6, oral NSAIDs n = 9, topical NSAIDs n = 8, COX
      2 inhibitors n = 9, and opioids n = 11). Relative (%) changes in pain were found
      to be as follows: acetaminophen = 32.5, oral NSAIDs = 34.3, topical NSAIDs =
      40.9, COX-2 inhibitors = 36.9, and opioids = 35.4. CONCLUSION: The effects of 5
      major drug categories in the treatment of OA pain were reviewed with data
      extracted from 29 studies published from 2006 to 2016. Acetaminophen was found to
      have an RC value close to that of oral NSAIDs. The effects of oral NSAIDs, COX-2
      inhibitors, and opioids in controlling pain were similar to what has been
      demonstrated in previous literature. Topical NSAIDs were found to have a greater
      RC than oral NSAIDs.

PMID- 30120511
TI  - [Meeting Report of the Uropathology Working Group of the German Society of
      Pathology, 2018].

PMID- 30120513
TI  - Exponential equilibration of genetic circuits using entropy methods.
AB  - We analyse a continuum model for genetic circuits based on a partial integro
      differential equation initially proposed in Friedman et al. (Phys Rev Lett
      97(16):168302, 2006) as an approximation of a chemical master equation. We use
      entropy methods to show exponentially fast convergence to equilibrium for this
      model with explicit bounds. The asymptotic equilibration for the multidimensional
      case of more than one gene is also obtained under suitable assumptions on the
      equilibrium stationary states. The asymptotic equilibration property for networks
      involving one and more than one gene is investigated via numerical simulations.

PMID- 30120512
TI  - [Ectopia of the pituitary].
AB  - The adenohypophysis has a large intrasellar part and two small parts at the
      pituitary stalk and the pharynx. Near this extrasellar pituitary tissue, and also
      in sinus sphenoidalis and sinus cavernosus, ectopic pituitary adenomas can
      develop. They are indistinguishable in structure and function from usual
      intrasellar adenomas. The neurohypophysis can show dystopias within complex
      malformations. In so-called pituitary stalk interruption syndrome, a real ectopia
      of the neurohypophysis is found at the eminentia mediana of the hypothalamus.
      Ectopic tissue in the pituitary is extremely rare: foci of ganglionic cells were
      found in the neurohypophysis and adrenocortical tissue in the adenohypophysis.
      Focal squamous epithelia in the anterior pituitary are a common finding but they
      are rather metaplastic from parenchymal cells than ectopic tissue. Small foci of
      ectopic salivary gland tissue are not rare in the intermediate zone.

PMID- 30120514
TI  - Inter-radiologist agreement using Society of Abdominal Radiology-American
      Gastroenterological Association (SAR-AGA) consensus nomenclature for reporting CT
      and MR enterography in children and young adults with small bowel Crohn disease.
AB  - PURPOSE: To assess inter-radiologist agreement using the Society of Abdominal
      Radiology-American Gastroenterological Association (SAR-AGA) consensus
      recommendations for reporting CT/MR enterography exams in pediatric and young
      adult small bowel Crohn disease (CD). METHODS: Institutional review board
      approval was obtained for this HIPAA-compliant retrospective investigation; the
      requirement for informed consent was waived. 25 CT and 25 MR enterography exams
      performed in children and young adults (age range: 6-23 years) between January
      2015 and April 2017 with a distribution of ileal CD severity (phenotype) were
      identified: normal or chronic CD without active inflammation (40%), active
      inflammatory CD (20%), stricturing CD (20%), and penetrating CD (20%). Five
      fellowship-trained pediatric radiologists, blinded to one another, documented key
      imaging findings and standardized impressions based on SAR-AGA consensus
      recommendations. Inter-radiologist agreement was evaluated using Fleiss' multi
      rater kappa statistic (kappa) with 95% confidence intervals (CI). RESULTS: Inter
      radiologist agreement was moderate for all key imaging findings except presence
      of ulcerations (kappa 0.37 [95% CI 0.28-0.46]) and sacculations (kappa 0.31 [95%
      CI 0.23-0.40]). Agreement for standardized impressions was substantial for
      stricturing disease (kappa 0.79 [95% CI 0.70-0.87]) and moderate for presence of
      inflammation (kappa 0.49 [95% CI 0.44-0.56]) and penetrating disease (kappa 0.58
      [95% CI 0.49-0.67]). No significant difference in agreement was found between CT
      and MRI. CONCLUSIONS: Agreement among five pediatric radiologists was moderate to
      substantial for SAR-AGA standardized impressions and fair to moderate for key
      imaging findings of pediatric and young adult CD.

PMID- 30120515
TI  - Virtual monoenergetic reconstruction of contrast-enhanced CT scans of the abdomen
      and pelvis at 40 keV improves the detection of peritoneal metastatic deposits.
AB  - PURPOSE: To evaluate the role of virtual monoenergetic imaging (VMI) in the
      detection of peritoneal metastatic disease in contrast-enhanced computed
      tomography (CT) of the abdomen and pelvis and to compare this technique to the
      conventional 120 kV mixed dataset. MATERIALS AND METHODS: Institutional review
      board approval was obtained with no informed consent required for this
      retrospective analysis. 43 consecutive patients with histopathologically
      confirmed peritoneal disease were scanned using a standard protocol on a 128
      section dual-source, dual-energy CT system (100/140 keV). Scans were
      retrospectively reconstructed at VMI energy levels from 40-110 keV in 10 keV
      increments and were analyzed both quantitatively and qualitatively. CNR values
      for peritoneal metastatic deposits were recorded using region of interest (ROI)
      analysis at each energy level for all VMI datasets. Subjective analysis was
      performed by two independent fellowship-trained readers with combined experience
      of greater than 15 years. Qualitative parameters included diagnostic
      acceptability, subjective noise, and contrast resolution and confidence. RESULTS:
      The contrast-to-noise ratios (CNRs) for peritoneal metastatic deposits at the
      different VMI energy levels were compared using a one-way ANOVA with Tukey Post
      Test, and the optimal CNR was observed at 40 keV (p < 0.0001). Qualitative
      parameters were compared using a Paired T Test. Subjective noise, diagnostic
      acceptability, and contrast resolution was significantly better on the
      conventional images, but readers reported increased confidence on VMI at 40 keV
      (p < 0.001). CONCLUSION: VMI reconstruction of contrast-enhanced dual-energy CT
      scans of the abdomen and pelvis at 40 keV maximizes the conspicuity of metastatic
      peritoneal deposits and improves radiologists' diagnostic confidence compared
      with conventional CT images. We recommend using virtual monoenergetic datasets at
      40 keV as a tool for improving the detection of these lesions in routine clinical
      practice.

PMID- 30120517
TI  - Opinions on Treatment of Breast Animation Deformity with Selective Nerve
      Ablation.

PMID- 30120516
TI  - New generation Hydrogel Endovascular Aneurysm Treatment Trial (HEAT): a study
      protocol for a multicenter randomized controlled trial.
AB  - PURPOSE: Aneurysm recanalization constitutes a limitation in the endovascular
      treatment of intracranial aneurysms using conventional bare platinum coils. The
      development of platinum coils coupled with hydrogel polymers aimed at decreasing
      the rates of recurrence by way of enhanced coil packing density and biological
      healing within the aneurysm. While enhanced occlusion and durability has been
      shown for the first generation hydrogel coils, their use was limited by technical
      challenges. Less data is available regarding the second-generation hydrogel coils
      which have been designed to perform like bare platinum coils. METHODS: The new
      generation Hydrogel Endovascular Aneurysm Treatment Trial (HEAT) is a
      multicenter, randomized controlled trial that compares the health outcomes of the
      second-generation HydroCoil Embolic System with bare platinum coils in the
      endovascular intracranial aneurysms. The primary endpoint is aneurysm recurrence,
      defined as any progression on the Raymond aneurysm scale, over a 24-month follow
      up period. Secondary endpoints include packing density, functional independence,
      procedural adverse events, mortality rate, initial complete occlusion, aneurysm
      retreatment, hemorrhage from treated aneurysm, and any aneurysm recurrence.
      RESULTS: Patient recruitment initiated in June 2011 and ended in January 2016 in
      46 centers. Six hundred eligible patients diagnosed with an intracranial
      aneurysm, ruptured or unruptured were randomly assigned to one of the two
      treatment arms. CONCLUSION: The HEAT trial compares the durability, imaging, and
      clinical outcomes of the second-generation hydrogel versus bare platinum coils in
      the endovascular treatment of ruptured or unruptured intracranial aneurysms. The
      results of this trial may further inform current endovascular treatment
      guidelines based on observed long-term outcomes.

PMID- 30120518
TI  - Assessment of Subject and Physician Satisfaction after Long-Term Treatment of
      Glabellar Lines with AbobotulinumtoxinA (Dysport(r)/Azzalure(r)): Primary Results
      of the APPEAL Noninterventional Study.
AB  - BACKGROUND: Although the short- and long-term effectiveness of abobotulinumtoxinA
      (Dysport(r)/Azzalure(r)) for glabellar line (GL) treatment is well established,
      reporting of subject satisfaction over repeat treatment cycles is limited. The
      APPEAL study aimed to assess subject satisfaction with long-term GL treatment
      with abobotulinumtoxinA in a real-life setting. METHODS: APPEAL was a
      noninterventional, prospective, longitudinal study in subjects administered >= 3
      abobotulinumtoxinA injection cycles for moderate-to-severe GL, according to
      routine clinical practice. Subjects completed a satisfaction questionnaire at 3
      weeks (+/- 7 days) after each cycle. Primary endpoint included subjects' overall
      satisfaction with GL after three injection cycles. Secondary endpoints included
      satisfaction after Cycles 1 and 2 and factors associated with satisfaction after
      each cycle. Physician satisfaction was also assessed after Cycles 1 and 3.
      RESULTS: Of 150 subjects enrolled, 135 completed the overall subject satisfaction
      questionnaire after Cycle 3. At 3 weeks after Cycle 3, 99.3% of subjects were
      'very satisfied' (74.1%) or 'satisfied' (25.2%) with GL. Levels of subject
      satisfaction and associated factors after Cycles 1 and 2 were as large and
      significant as after Cycle 3 (83-100%, depending on question). Physicians'
      satisfaction with GL appearance, facial expression, and overall satisfaction was
      almost complete after the first injection (>= 97.4%) and unanimous after the
      third (100%). CONCLUSIONS: In the APPEAL study, overall satisfaction was high
      after three abobotulinumtoxinA injection cycles for GL based on both subjects'
      (99.3%) and physicians' (100.0%) assessments. High levels of subject satisfaction
      reported after Cycle 1 were maintained with repeated injections. No new safety
      signals were observed. LEVEL OF EVIDENCE IV: This journal requires that authors
      assign a level of evidence to each article. For a full description of these
      Evidence-Based Medicine ratings, please refer to the Table of Contents or the
      online Instructions to Authors www.springer.com/00266 . Trial registration
      NCT02353897.

PMID- 30120519
TI  - 3'untranslated regions: regulation at the end of the road.
AB  - Post-transcriptional gene regulation in bacteria plays a major role in the
      adaptation of bacterial cells to the changing conditions encountered in the
      environment. In bacteria, most of the regulation at the level of mRNA seems to be
      targeting the 5'untranslated regions where accessibility to the ribosome-binding
      site can be modulated to alter gene expression. In recent years, the role of
      3'untranslated regions has gained attention also as a site for post
      transcriptional regulation. In addition to be a source of trans-encoded small
      RNAs, the 3'untranslated regions can be targets to modulate gene expression.
      Taking recent findings in the post-transcriptional regulation of the hilD gene,
      encoding for the main regulator of virulence in Salmonella enterica serovar
      Typhimurium, we highlight the role of 3'untranslated regions as targets of post
      transcriptional regulation mediated by small RNAs and discuss the implications of
      transcriptional elongation in the 3'UTR-mediated regulation in bacteria.

PMID- 30120521
TI  - Levansucrase from Halomonas smyrnensis AAD6T: first halophilic GH-J clan enzyme
      recombinantly expressed, purified, and characterized.
AB  - Fructans, homopolymers of fructose produced by fructosyltransferases (FTs), are
      emerging as intriguing components in halophiles since they are thought to be
      associated with osmotic stress tolerance and overall fitness of microorganisms
      and plants under high-salinity conditions. Here, we report on the full
      characterization of the first halophilic FT, a levansucrase from Halomonas
      smyrnensis AAD6T (HsLsc; EC 2.4.1.10). The encoding gene (lsc) was cloned into a
      vector with a 6xHis Tag at its C-terminus, then expressed in Escherichia coli.
      The purified recombinant enzyme (47.3 kDa) produces levan and a wide variety of
      fructooligosaccharides from sucrose, but only in the presence of high salt
      concentrations (> 1.5 M NaCl). HsLsc showed Hill kinetics and pH and temperature
      optima of 5.9 and 37  degrees C, respectively. Interestingly, HsLsc was still
      very active at salt concentrations close to saturation (4.5 M NaCl) and was
      selectively inhibited by divalent cations. The enzyme showed high potential in
      producing novel saccharides derived from raffinose as both fructosyl donor and
      acceptor and cellobiose, lactose, galactose, and L-arabinose as fructosyl
      acceptors. With its unique biochemical characteristics, HsLsc is an important
      enzyme for future research and potential industrial applications in a world faced
      with drought and diminishing freshwater supplies.

PMID- 30120520
TI  - Sodium chloride improves pullulan production by Aureobasidium pullulans but
      reduces the molecular weight of pullulan.
AB  - The effect of sodium chloride (NaCl) on pullulan production by batch culture of
      Aureobasidium pullulans CCTCC M 2012259 was investigated. NaCl at 3 g/L improved
      the pullulan titer by 26.7% but reduced the molecular weight of pullulan to only
      46.8% of that obtained in the control without NaCl. In order to elucidate the
      physiological mechanism underlying the effect of NaCl on pullulan production,
      assays of key enzyme activity, gene expression, energy metabolism, and
      intracellular uridine diphosphate glucose (UDP-glucose) content were performed.
      Results indicated that NaCl increased the activities of alpha-phosphoglucose
      mutase and glucosyltransferase involved in pullulan biosynthesis, increased the
      activities of alpha-amylase being responsible for pullulan degradation,
      upregulated the transcriptional levels of pgm1, fks, and amy2 genes, enhanced the
      driving force for ATP supply, and helped to maintain intracellular UDP-glucose at
      a high level in A. pullulans CCTCC M 2012259. All these results illuminate the
      reason by which NaCl increases pullulan titer but reduces the molecular weight of
      pullulan.

PMID- 30120522
TI  - Antioxidant activities of four superoxide dismutases in Metarhizium robertsii and
      their contributions to pest control potential.
AB  - The superoxide dismutase (SOD) family of Metarhizium robertsii, a fungal insect
      pathogen, comprises six members functionally unknown yet, including Cu/ZnSODs
      (Sod1/5/6), MnSODs (Sod2/3), and FeSOD (Sod4). Here, we show a mitochondrial
      localization of Sod3 and Sod4 and a requirement of either sod4 or sod6 for the
      fungal life as suggested by an inability to be deleted. We found remarked roles
      of Sod1, Sod2, and Sod3 in sustaining antioxidant activity and the fungal
      potential against insect pests but no role of Sod5 in all examined phenotypes.
      Intracellular SOD activity decreased by 49% in Deltasod1 and 22% in either
      Deltasod2 or Deltasod3. The decreased SOD activities concurred with altered
      enzymographs, in which one of two SOD-active bands in wild-type and rescued
      strains disappeared in Deltasod1 rather than in Deltasod2 and another band
      disappeared in Deltasod3. Consequently, maximal cell sensitivity to superoxide
      anions generated by oxidant menadione occurred in Deltasod1, followed
      sequentially by Deltasod3 and Deltasod2. The latter two mutants were more
      sensitive than Deltasod1 to oxidant H2O2. Transcriptional analysis revealed
      partial compensation of one or two partner genes upregulated for the absence of
      sod1, sod2, or sod3 and full compensation of three partners largely upregulated
      for the absence of sod5, as well as differential expression of most catalase
      genes in each Deltasod mutant. The three mutants also suffered defects in
      conidial thermotolerance, UVB resistance, and virulence. These findings unveil
      that, to adapt to different host spectra and habitats, some major SODs in M.
      roberstii are functionally differentiated from those known previously in
      Beauveria bassiana, a classic insect mycopathogen lacking Sod6.

PMID- 30120523
TI  - Metabolic engineering of Bacillus subtilis for the co-production of uridine and
      acetoin.
AB  - In this study, a uridine and acetoin co-production pathway was designed and
      engineered in Bacillus subtilis for the first time. A positive correlation
      between acetoin and uridine production was observed and investigated. By
      disrupting acetoin reductase/2,3-butanediol dehydrogenasegenebdhA, the acetoin
      and uridine yield was increased while 2,3-butanediol formation was markedly
      reduced. Subsequent overexpression of the alsSD operon further improved acetoin
      yield and abolished acetate formation. After optimization of fermentation medium,
      key supplementation strategies of yeast extract and soybean meal hydrolysate were
      identified and applied to improve the co-production of uridine and acetoin. With
      a consumption of 290.33 g/L glycerol, the recombinant strain can accumulate 40.62
      g/L uridine and 60.48 g/L acetoin during 48 h of fed-batch fermentation. The
      results indicate that simultaneous production of uridine and acetoin is an
      efficient strategy for balancing the carbon metabolism in engineered Bacillus
      subtilis. More importantly, co-production of value-added products is a possible
      way to improve the economics of uridine fermentation.

PMID- 30120524
TI  - Adhesion of Rhodococcus ruber IEGM 342 to polystyrene studied using contact and
      non-contact temperature measurement techniques.
AB  - Adhesion of industrially important bacteria to solid carriers through the example
      of actinobacterium Rhodococcus ruber IEGM 342 adhered to polystyrene was studied
      using real-time methods, such as infrared (IR) thermography and thermometry with
      platinum resistance (PR) detectors. Dynamics of heat rate and heat production was
      determined at early (within first 80 min) stages of rhodococcal cell adhesion.
      Heat rate was maximal (1.8 * 10-3-2.7 * 10-3 W) at the moment of cell loading.
      Heat production was detected for the entire length of adhesion, and its dynamics
      depended on concentration of rhodococcal cells. At high (1 * 1010 CFU/ml) cell
      concentration, a stimulative (in 1.7 and 1.4 times consequently) effect of
      polystyrene treatment with Rhodococcus-biosurfactant on the number of adhered
      rhodococcal cells and cumulative heat production at rhodococcal cell adhesion was
      revealed. The values of heat flows (heat rate 0.3 * 10-3-2.7 * 10-3 W, heat
      production up to 8.2 * 10-3 J, and cumulative heat production 0.20-0.53 J) were 5
      30 times higher than those published elsewhere that indicated high adhesive
      activity of R. ruber IEGM 342 towards polystyrene. To analyze experimental
      results and predict effects of boundary conditions on the temperature
      distribution, a mathematical model for heating a polystyrene microplate with
      distributed heat sources has been developed. Two independent experimental methods
      and the numerical modeling make it possible to verify the experimental results
      and to propose both contact and non-contact techniques for analyzing kinetics of
      bacterial adhesion.

PMID- 30120525
TI  - Autophagy gene overexpression in Saccharomyces cerevisiae perturbs subcellular
      organellar function and accumulates ROS to accelerate cell death with relevance
      to sparkling wine production.
AB  - Traditional sparkling wines are produced by the refermentation of a base wine
      with yeast in the bottle followed by a critical period of aging. During the often
      lengthy aging process, yeast undergoes cell death and autolysis to release
      cellular compounds that over time ultimately contribute to the flavor and
      appearance of the product. While accelerating yeast autolysis for sparkling wine
      production has been the focus of several studies, employing overexpressed native
      yeast alleles for this purpose remains poorly explored. Here, we show that the
      overexpression of native yeast genes, specifically selected autophagic genes,
      results in accelerated cell death in nitrogen starvation and base wine
      refermentation. We show ATG3 or ATG4 overexpression has pleiotropic intracellular
      ramifications including reduced turnover of autophagic cargo, vacuolar
      fragmentation, abnormal accumulation of lipids, and accelerated accumulation of
      reactive oxygen species (ROS), all of which precede accelerated cell death. Our
      findings suggest that the increased expression of autophagy-related genes, such
      as ATG3 and ATG4, in industrial wine yeast can serve as a suitable marker or
      breeding strategy to accelerate the cell death and autolysis of wine yeast during
      sparkling wine production.

PMID- 30120526
TI  - Design and production of a novel antimicrobial fusion protein in Escherichia
      coli.
AB  - In recent years, antimicrobial peptides (AMPs) have attracted increasing
      attention. The microbial cells provide a simple, cost-effective platform to
      produce AMPs in industrial quantities. While AMP production as fusion proteins in
      microorganisms is commonly used, the recovery of AMPs necessitates the use of
      expensive proteases and extra purification steps. Here, we develop a novel fusion
      protein DAMP4-F-pexiganan comprising a carrier protein DAMP4 linked to the AMP,
      pexiganan, through a long, flexible linker. We show that this fusion protein can
      be purified using a non-chromatography approach and exhibits the same
      antimicrobial activity as the chemically synthesized pexiganan peptide without
      any cleavage step. Activity of the fusion protein is dependent on a long,
      flexible linker between the AMP and carrier domains, as well as on the expression
      conditions of the fusion protein, with low-temperature expression promoting
      better folding of the AMP domain. The production of DAMP4-F-pexiganan circumvents
      the time-consuming and costly steps of chromatography-based purification and
      enzymatic cleavages, therefore shows considerable advantages over traditional
      microbial production of AMPs. We expect this novel fusion protein, and the
      studies on the effect of linker and expression conditions on its antimicrobial
      activity, will broaden the rational design and production of antimicrobial
      products based on AMPs.

PMID- 30120527
TI  - Brevundimonas mongoliensis sp. nov., A Novel Psychrotolerant Bacterium Isolated
      from Oil-Contaminated Soil.
AB  - Two yellow-coloured, Gram-stain-negative, motile, and rod-shaped bacteria,
      designated strains R-10-10T and R-10-15 were isolated from oil-contaminated soil.
      Both strains were able to grow at 4-40  degrees C, pH 5.5-10.5, and 0-4% (w/v)
      NaCl concentration. These strains were taxonomically characterized by a
      polyphasic approach. Based on the 16S rRNA gene sequence analysis, both strains,
      R-10-10T and R-10-15, could be affiliated to the genus Brevundimonas and shared
      highest sequence similarity with Brevundimonas staleyi FWC43T (98.8%),
      Brevundimonas bullata TK0051T (98.6%), and Brevundimonas subvibrioides CB81T
      (98.3%). The pairwise sequence similarity between strains R-10-10T and R-10-15
      was 99.9%. Both strains R-10-10T and R-10-15 contained phosphatidylglycerol,
      diphosphatidylglycerol, and four unidentified glycolipids as major polar lipids;
      ubiquinone-10 as sole respiratory quinone; and summed feature 8 (C18:1omega7c
      and/or C18:1omega6c), C16:0, summed feature 3 (C16:1omega7c and/or C16:1omega6c),
      and C18:1omega9c as major fatty acids. The genomic DNA G+C content values of
      strains R-10-10T and R-10-15 were 67.1 and 66.9 mol%, respectively. The DNA-DNA
      relatedness between R-10-10T and R-10-15 was higher than 70% but the values were
      less than 55% with closely related reference type strains. The morphological,
      physiological, chemotaxonomic, and phylogenetic data clearly distinguished strain
      R-10-10T from its closest phylogenetic neighbors. Thus, strain R-10-10T is
      considered to represent a novel species of the genus Brevundimonas, for which the
      name Brevundimonas mongoliensis sp. nov. is proposed. The type strain is R-10-10T
      (=KEMB 9005-696T = KACC 19387T = JCM 32172T), and strain R-10-15 is considered as
      an additional strain of the novel species.

PMID- 30120528
TI  - Discrimination of Human Pathogen Clostridium Species Especially of the
      Heterogeneous C. sporogenes and C. botulinum by MALDI-TOF Mass Spectrometry.
AB  - Clostridium species cause several local and systemic diseases. Conventional
      identification of these microorganisms is in part laborious, not always reliable,
      time consuming or does not always distinguish different species, i.e., C.
      botulinum and C. sporogenes. All in, there is a high interest to find out a
      reliable, powerful and rapid method to identify Clostridium spp. not only on
      genus but also on species level. The aim of the present study was to identify
      Clostridium spp. strains and also to find differences and metabolic groups of C.
      botulinum by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass
      Spectrometry (MALDI-TOF MS). A total of 123 strains of Clostridium spp. (C.
      botulinum, n = 40, C. difficile, n = 11, C. tetani, n = 11, C. sordellii, n = 20,
      C. sporogenes, n = 18, C. innocuum, n = 10, C. perfringens, n = 13) were analyzed
      by MALDI-TOF MS in combination with methods of multivariate statistical analysis.
      MALDI-TOF MS analysis in combination with methods of multivariate statistical
      analysis was able to discriminate between the different tested Clostridium spp.,
      even between species which are closely related and difficult to differentiate by
      traditional methods, i.e., C. sporogenes and C. botulinum. Furthermore, the
      method was able to separate the different metabolic groups of C. botulinum.
      Especially, E gene-positive C. botulinum strains are clearly distinguishable from
      the other species but also from those producing other toxin types. Thus, MALDI
      TOF MS represents a reliable and above all quick method for identification of
      cultivated Clostridium species.

PMID- 30120529
TI  - Ultrasound Evaluation of Puncture Sites After Deployment of Two Different Types
      of Vascular Closure Devices: A Prospective Comparative Study.
AB  - PURPOSE: The aim of this study was to compare the ultrasonographic findings of
      femoral puncture sites and the complications of Perclose ProGlide(r) and
      FemoSealTM after neurointerventional procedures. METHODS: In this prospective,
      single-center study, we randomly assigned 155 femoral puncture sites to treatment
      with Perclose ProGlide(r) or FemoSealTM. We hypothesized that the two different
      types of VCD cause different vascular changes. Ultrasonography of the femoral
      puncture sites was performed 24 h after the procedure and at an outpatient visit
      after 6 months. The intima-media thickness (IMT), vessel diameter, and minimal
      luminal diameter of the common femoral artery were measured; the perivascular
      soft tissue change and absorption of the hemostatic material were observed. The
      device failure rate and vascular complications associated with each device were
      also evaluated. RESULTS: Follow-up ultrasonography was performed at a median
      follow-up time of 187.0 days (range 147-240 days) after the initial
      ultrasonography. The IMT on follow-up ultrasonography was significantly higher in
      patients who received FemoSealTM (P = 0.0000). Intimal hyperplasia and partial
      absorption of the hemostatic material were significantly more frequent in
      patients who received FemoSealTM. The vessel diameters on initial and follow-up
      ultrasonography were not significantly different, but the minimal diameter on
      follow-up ultrasonography was significantly lower in patients who received
      FemoSealTM. Device failure and pseudoaneurysms occurred at 9 and 3 puncture sites
      in patients who received Perclose ProGlide(r), respectively. CONCLUSIONS: Intimal
      hyperplasia was more frequently observed in patients who received FemoSealTM.
      However, more device failures and pseudoaneurysms occurred in patients who
      received Perclose ProGlide(r). LEVEL OF EVIDENCE: Step 2 (level 2).

PMID- 30120531
TI  - Antiplatelet Therapy is Associated with Stent Patency After Iliocaval Venous
      Stenting.
AB  - PURPOSE: To examine the effectiveness of antithrombotic medications to prevent
      venous stent malfunction for iliocaval occlusive disease. MATERIALS AND METHODS:
      A retrospective analysis was performed on 62 patients who underwent technically
      successful endovascular iliocaval stent placement between May 2008 and April
      2017. Clinical records were reviewed for demographic information, procedure
      details, post-stenting antithrombotic prophylaxis and stent patency on follow-up.
      Stent malfunction was defined as > 50% stenosis or occlusion at follow-up. Risk
      factors for stent malfunction were assessed with univariable and multiple Cox
      proportional hazard models. RESULTS: The median follow-up period was 11.6 months
      (range 0.1-76.4). Overall primary and secondary cumulative patency rates at 12
      months were 70.0% and 92.4%, respectively. After stent placement, 97% of patients
      received anticoagulation with warfarin, enoxaparin or a factor Xa inhibitor. In
      addition, 61% received antiplatelet prophylaxis with aspirin, clopidogrel or a
      combination. In multiple Cox regression analysis, post-stenting antiplatelet use
      remained significantly associated with primary stent patency (HR = 0.28, P =
      0.022). CONCLUSION: After iliocaval venous stenting, stent patency was best
      predicted by concomitant antiplatelet and anticoagulation therapy rather than
      anticoagulation alone. This novel finding warrants further research underlying
      mechanisms leading to venous stent thrombosis, and has implications for optimal
      medical management after venous stenting.

PMID- 30120530
TI  - Case Series of Aortic Arch Aneurysm in Patients with Bovine Arch Treated with
      Proximal Scalloped and Fenestrated Stent Graft.
AB  - PURPOSE: The bovine arch is the most common variant of the aortic arch and occurs
      when the innominate artery shares a common origin with the left common carotid
      artery. We report an endovascular repair of aortic arch aneurysm in patients with
      a bovine arch using the Najuta proximal scalloped and fenestrated stent graft.
      MATERIALS AND METHODS: Thoracic endovascular aneurysm repairs using the Najuta
      stent graft were performed at our facility. It was inserted and deployed at a
      zone 0 with precise positional adjustment of the scallop of the stent graft to
      the brachiocephalic trunk. RESULTS: Overall, eight patients with bovine aortic
      arch were treated with fenestrated endovascular aneurysm repair. Technical
      success was 100% with no 30-day death. The follow-up period ranged from 7 to 29
      (median 12) months. None of the patients had a stroke or paraplegia, and no
      endoleak was observed. All brachiocephalic trunks scalloped, and the left
      subclavian artery fenestrated vessels remained patent during the follow-up
      period. CONCLUSION: The Najuta stent graft repair of aortic arch aneurysms in
      patients with a bovine arch is a safe and effective treatment option, with good
      immediate and short-term results.

PMID- 30120532
TI  - Limited reliability of grading scapular notching according to Nerot-Sirveaux on
      anteroposterior radiographs.
AB  - INTRODUCTION: Incidences of scapular notching (SN) in reverse shoulder
      arthroplasty (RSA) range between 0% and 96%, and controversy remain as to its
      relevance for patient outcome. We assessed the reliability of scapular notching
      (SN) grading based on the Sirveaux classification system using anteroposterior
      radiographs. MATERIALS AND METHODS: 206 RSA procedures with 5-year postoperative
      anteroposterior shoulder radiographs were classified independently by seven
      assessors according to Sirveaux (session 1). After a review meeting, three
      assessors re-classified the radiographs along with quality criteria (session 2).
      SN grading by the majority of assessors was taken as the reference.
      Classification interobserver reliability was analyzed using Kappa statistics.
      RESULTS: The incidence of SN was estimated at 53% and 37% at the first and second
      sessions, respectively. Interobserver reliability Kappa coefficients resulting
      from the first and second sessions were 0.27 and 0.43, respectively. Case
      selection based on radiographic quality criteria did not improve SN grading
      reliability in the second session. CONCLUSION: Agreement between individual
      surgeons was low when grading SN in RSA according to Sirveaux using
      anteroposterior radiographs. Consensus among several assessors may increase
      reliability in research settings.

PMID- 30120533
TI  - Osteogenic sarcoma of the skull: long-term outcome of a rare tumor.
AB  - BACKGROUND: Osteogenic sarcoma of the skull is uncommon and long-term outcome is
      not well defined. We review the literature and present a pediatric case of
      calvarial osteogenic sarcoma with good long-term oncological and cosmetic outcome
      and excellent quality of life. This case presented major surgical challenges,
      which are detailed. CASE DESCRIPTION: A 6-year-old boy presented with a painless
      5 cm * 5 cm lump over the vertex region. He was neurologically normal. Imaging
      showed an extensive bony lesion with intradural extension. After incisional
      biopsy showed probable low grade osteosarcoma, a complete en bloc resection with
      margins was attempted via a concentric craniotomy around the lesion after
      embolization to reduce blood loss. Invasion of the brain by the tumor precluded
      the complete en bloc resection, but gross total resection was achieved. The final
      pathology was consistent with a low-grade osteosarcoma and adjuvant chemotherapy
      was provided. Follow-up for 8 years has shown no recurrence with good cosmetic
      and functional outcome.

PMID- 30120535
TI  - Advantages of creation of holes and removal of air in artificial bone for early
      bone formation when used artificial bone as a gap filler in open wedge high
      tibial osteotomy.
AB  - Recently, many facilities perform open wedge high tibial osteotomy (OWHTO) using
      artificial bone as a gap filler. However, there are many cases in which
      artificial bone is used without a clear purpose. We recommend a surgical
      technique to promote early synostosis between artificial bone and recipient bone
      due to mechanical support especially in the early stage after OWHTO. At our
      hospital, beta-tricalcium phosphate (beta-TCP) with 60% porosity is used in
      OWHTO. Initially, a wedge-shaped block-type beta-TCP, as large as possible, was
      inserted into the gap. However, from the standpoint of initial mechanical
      support, we changed the artificial bone size and created intentional holes.
      Furthermore, we removed air bubbles from beta-TCP. We evaluated the synostosis on
      the basis of clinical results and diagnostic imaging. As a result of creating
      holes and removing air from the artificial bone, a trend toward faster synostosis
      was noted, especially at the early stage. No adverse events such as tibial
      plateau fracture, lateral cortical fracture, plate and screw failure and
      correction loss due to reducing the size of the artificial bone occurred, but
      placement of the artificial bone in contact with cortical bone and surface
      contact installation with the recipient bone tissue was important. When using
      artificial bone in OWHTO, holes formation and removal of air from the artificial
      bone are recommended for faster synostosis between artificial bone and recipient
      bone in the early stage after surgery. Artificial bone should be used, with
      attention to its positioning and shape, for efficient mechanical support.

PMID- 30120534
TI  - Psychiatric comorbidity as a risk factor for mortality in people with anorexia
      nervosa.
AB  - Anorexia nervosa (AN) is found associated with increased mortality. Frequent
      comorbidities of AN include substance use disorders (SUD), affective disorders
      (AD) and personality disorders (PD). We investigated the influence of these
      psychiatric comorbidities on all-cause mortality with demographic and
      socioeconomic factors considered as confounders in the observation window between
      January 2007 and March 2016 for 1970 people with AN, using data from the case
      register of the South London and Maudsley (SLaM) NHS Foundation Trust, an almost
      monopoly-secondary mental healthcare service provider in southeast London. We
      retrieved data from its Clinical Records Interactive Search (CRIS) system as data
      source. Mortality was ascertained through nationwide tracing by the UK Office for
      National Statistics (ONS) linked to CRIS database on a monthly basis. A total of
      43 people with AN died during the observation period. Standardized Mortality
      Ratio (SMR) with England and Wales population in 2012 as standard population for
      our study cohort was 5.21 (95% CI 3.77, 7.02). In univariate analyses, the
      comorbidity of SUD or PD was found to significantly increase the relative risks
      of mortality (HRs = 3.10, 95% CI 1.21, 7.92; and 2.58, 95% CI 1.23, 5.40,
      respectively). After adjustment for demographic and socioeconomic covariates as
      confounders, moderately but not significantly elevated risks were identified for
      SUD (adjusted HR = 1.39, 95% CI 0.53, 3.65) and PD (adjusted HR = 1.58, 95% CI
      0.70, 3.56). These results suggest an elevated mortality in people with AN, which
      might be, at least partially, explained by the existence of the comorbidities SUD
      or PD.

PMID- 30120536
TI  - Analysis of risk factors for perioperative mortality in elderly patients with
      intertrochanteric fracture.
AB  - OBJECTIVE: To investigate risk factors for perioperative death in elderly
      patients with intertrochanteric fracture. METHODS: Clinical data from 1051 cases
      with intertrochanteric fracture from March 2005 to March 2015 were reviewed and
      analyzed, and causes of death during the perioperative period were statistically
      analyzed. Various indicators were compared by t test and chi2 test. Multivariate
      analysis was performed using non-conditional logistic regression analysis.
      RESULTS: Chronic diseases of major organs (heart, brain, and lung), postoperative
      complications, and various indicators within 24 h after admission (albumin,
      hemoglobin, brain natriuretic peptide [BNP], glucose, creatinine, arterial blood
      pH, PaO2, and APACHE II) were statistically significantly different between
      patients who survived and those who died. Logistic regression analysis indicated
      that postoperative complications, APACHE II score, BNP, and chronic diseases of
      major organs were the risk factors for perioperative mortality in elderly
      patients with intertrochanteric fracture. CONCLUSION: BNP and APACHE II score
      could be used as important reference indexes for predicting possible
      perioperative mortality in elderly patients with intertrochanteric fracture and
      chronic diseases of major organs. Complications after fracture may be also risk
      factors.

PMID- 30120537
TI  - [Suprachoroidal hydrogel buckling].
AB  - Suprachoroidal hydrogel buckling is a simple and safe procedure for the treatment
      of rhegmatogenous retinal detachment. The advantages of modern vitrectomy and
      classical buckling surgery are combined in this surgical approach. Suprachoroidal
      buckling can be performed as a stand-alone procedure or in addition to
      vitrectomy. Cross-linked hyaluronic acid with a resorption time of up to 8 weeks
      is a suitable agent for this technique. Further studies will help to establish
      suprachoroidal buckling as a surgical procedure for treatment of retinal
      detachment.

PMID- 30120538
TI  - Effect of industrial trans-fatty acids-enriched diet on gut microbiota of C57BL/6
      mice.
AB  - PURPOSE: Previous studies have shown that industrially originated trans-fatty
      acids (iTFAs) are associated with several chronic diseases, but the underlying
      mechanisms remain unknown. Because gut microbiota play a critical role in human
      health, diet competent induced gut microbiota dysbiosis may contributing to
      disease pathogenesis. Therefore, the present study examined the impact of iTFA on
      gut microbiota, help understanding the underling mechanism of iTFA-associated
      chronic diseases. METHODS: Forty male 8-week-old mice were divided into 4 groups
      and randomly assigned to diets containing soybean oil (non-iTFA) or partially
      hydrogenated soybean oil (iTFA). The intervention groups were: (1) low soybean
      oil (LS); (2) high soybean oil (HS); (3) low partially hydrogenated oil (LH) and
      (4) high partially hydrogenated oil (HH). The gut microbiota profiles were
      determined by 16S rRNA gene sequencing. Physiological parameters and the
      inflammatory status of the small intestine and other tissues were analyzed. Short
      chain fatty acid levels in feces were measured using gas chromatography. RESULTS:
      The intake of iTFA increased the abundance of well-documented 'harmful' bacteria,
      such as Proteobacteria and Desulfovibrionaceae (P < 0.05), whereas it decreased
      relative abundance of 'beneficial' bacteria, such as Bacteroidetes,
      Lachnospiraceae, Bacteroidales S24-7 (P < 0.05). Surprisingly, the intake of iTFA
      increased the abundance of the probiotic Lactobacillaceae (P < 0.05).
      Additionally, the intake of iTFA induced increase of inflammatory parameters, as
      well as a numerical decrease of fecal butyric acid and valeric acid. CONCLUSIONS:
      This study, to our knowledge, is the first to demonstrate that the consumption of
      iTFA resulted in a significant dysbiosis of gut microbiota, which may contribute
      to the development of chronic diseases associated with iTFA.

PMID- 30120540
TI  - Needle aspiration as an alternative treatment for glio-ependymal cysts.

PMID- 30120541
TI  - Unstable impedance of a single electrode contact resulting in loss of DBS therapy
      a case report.
AB  - Open and short circuits of electrode contacts are important technical
      dysfunctions of DBS. Here, we report on another type of dysfunction restricted to
      a single electrode contact: impedance instability within regular absolute values.
      After 9-year subthalamic DBS, a Parkinson patient developed unilateral motor
      symptoms and intermittent dysaesthesia due to impedance instability of the active
      contact. DBS efficacy could be restored without surgical revision by activation
      of the neighboring contact. During 3-year-follow-up, impedances of the
      dysfunctional contact varied between 1 and 3 kOmega whereas the other three
      contacts remained stable. Impedance documentation is crucial to identify such
      dysfunctions.

PMID- 30120539
TI  - Phenotypic characterization of diamond (dind), a Drosophila gene required for
      multiple aspects of cell division.
AB  - Many genes are required for the assembly of the mitotic apparatus and for proper
      chromosome behavior during mitosis and meiosis. A fruitful approach to elucidate
      the mechanisms underlying cell division is the accurate phenotypic
      characterization of mutations in these genes. Here, we report the identification
      and characterization of diamond (dind), an essential Drosophila gene required
      both for mitosis of larval brain cells and for male meiosis. Larvae homozygous
      for any of the five EMS-induced mutations die in the third-instar stage and
      exhibit multiple mitotic defects. Mutant brain cells exhibit poorly condensed
      chromosomes and frequent chromosome breaks and rearrangements; they also show
      centriole fragmentation, disorganized mitotic spindles, defective chromosome
      segregation, endoreduplicated metaphases, and hyperploid and polyploid cells.
      Comparable phenotypes occur in mutant spermatogonia and spermatocytes. The dind
      gene encodes a non-conserved protein with no known functional motifs. Although
      the Dind protein exhibits a rather diffuse localization in both interphase and
      mitotic cells, fractionation experiments indicate that some Dind is tightly
      associated with the chromatin. Collectively, these results suggest that loss of
      Dind affects chromatin organization leading to defects in chromosome condensation
      and integrity, which in turn affect centriole stability and spindle assembly.
      However, our results do not exclude the possibility that Dind directly affects
      some behaviors of the spindle and centrosomes.

PMID- 30120544
TI  - Change detection in complex auditory scenes is predicted by auditory memory,
      pitch perception, and years of musical training.
AB  - Our world is a sonically busy place and we use both acoustic information and
      experience-based knowledge to make sense of the sounds arriving at our ears. The
      knowledge we gain through experience has the potential to shape what sounds are
      prioritized in a complex scene. There are many examples of how visual expertise
      influences how we perceive objects in visual scenes, but few studies examine how
      auditory expertise is associated with attentional biases toward familiar real
      world sounds in complex scenes. In the current study, we investigated whether
      musical expertise is associated with the ability to detect changes to real-world
      sounds in complex auditory scenes, and whether any such benefit is specific to
      musical instrument sounds. We also examined whether change detection is better
      for human-generated sounds in general or only communicative human sounds. We
      found that musicians had less change deafness overall. All listeners were better
      at detecting human communicative sounds compared to human non-communicative
      sounds, but this benefit was driven by speech sounds and sounds that were vocally
      generated. Musical listening skill, speech-in-noise, and executive function
      abilities were used to predict rates of change deafness. Auditory memory, musical
      training, fine-grained pitch processing, and an interaction between training and
      pitch processing accounted for 45.8% of the variance in change deafness. To
      better understand perceptual and cognitive expertise, it may be more important to
      measure various auditory skills and relate them to each other, as opposed to
      comparing experts to non-experts.

PMID- 30120542
TI  - Low radiographic muscle density is associated with lower overall and disease-free
      survival in early-stage colorectal cancer patients.
AB  - BACKGROUND: In cancer patients with a poor prognosis, low skeletal muscle
      radiographic density is associated with higher mortality. Whether this
      association also holds for early-stage cancer is not very clear. We aimed to
      study the association between skeletal muscle density and overall mortality among
      early-stage (stage I-III) colorectal cancer (CRC) patients. Furthermore, we
      investigated the association between skeletal muscle density and both CRC
      specific mortality and disease-free survival in a subset of the study population.
      METHODS: Skeletal muscle density was assessed in 1681 early-stage CRC patients,
      diagnosed between 2006 and 2015, using pre-operative computed tomography images.
      Adjusted Cox proportional hazard models were used to evaluate the association
      between muscle density and overall mortality, CRC-specific mortality and disease
      free survival. RESULTS: The median follow-up time was 48 months (range 0-119
      months). Low muscle density was detected in 39% of CRC patients. Low muscle
      density was significantly associated with higher mortality (low vs. normal:
      adjusted HR 1.91, 95% CI 1.53-2.38). After stratification for comorbidities, the
      association was highest in patients with >= 2 comorbidities (HR 2.11, 95% CI 1.55
      2.87). Furthermore, low skeletal muscle density was significantly associated with
      poorer disease-free survival (HR 1.68, 95% CI 1.14-2.47), but not with CRC
      specific mortality (HR 1.68, 95% CI 0.89-3.17) in a subset of the study
      population. CONCLUSION: In early-stage CRC patients, low muscle density was
      significantly associated with higher overall mortality, and worse disease-free
      survival.

PMID- 30120543
TI  - Hangzhou criteria are more accurate than Milan criteria in predicting long-term
      survival after liver transplantation for HCC in Germany.
AB  - BACKGROUND: Milan criteria are used for patient selection in liver
      transplantation for hepatocellular carcinoma (HCC). Hangzhou criteria have been
      shown in China to enable access to liver transplantation for more patients when
      compared to Milan criteria without negative effects on long-term survival. The
      purpose of this study was to evaluate the Hangzhou criteria in a German cohort.
      METHODS: One hundred fifty-nine patients transplanted for HCC between 1975 and
      2010 were investigated. Patients were categorized into four groups depending on
      the fulfillment of Milan and Hangzhou criteria. General and tumor baseline
      characteristics were compared. Overall and tumor-free survival rates were
      investigated with the Kaplan-Meier analysis. RESULTS: One-, 3-, 5-, and 10-year
      survival rates for patients fulfilling Milan criteria (n = 68) were 89.7, 83.7,
      75.8, and 62.1%, respectively, versus 89.8, 82.2, 75.2, and 62.6% for patients
      fulfilling Hangzhou criteria (n = 109) (p = 0.833). When comparing patients
      exceeding Milan or Hangzhou criteria, survival rates were 75.3, 53.2, 48.1, and
      41.1% versus 63.3, 31.4, 26.9, and 22.1%, respectively (p = 0.019). The
      comparison of tumor-free survival rates in patients fulfilling Milan or Hangzhou
      criteria was statistically not significant (p = 0.785), whereas the comparison of
      the groups exceeding the criteria showed significantly worse survival for
      patients outside Hangzhou criteria (p = 0.007). The proportion of patients
      fulfilling Hangzhou criteria (68.6%) was significantly larger as compared to the
      proportion fulfilling Milan criteria (42.8%) (p < 0.001). CONCLUSION: Hangzhou
      criteria are more accurate in predicting long-term survival after liver
      transplantation for HCC in Germany. Deployment of the Hangzhou criteria for
      patient selection could enlarge the pool of transplantable patients.

PMID- 30120545
TI  - Human papillomaviruses in Western Africa: prevalences and risk factors in Burkina
      Faso.
AB  - PURPOSE: Cervical cancer is the most common cancer in women in low income
      countries. Certain oncogenic types of human papillomaviruses are causally
      associated with the cervical cancer. To ensure effective primary prevention
      through the introduction of a national vaccination program in Burkina Faso,
      information about the disease burden of HPV infection in the country is of great
      importance. METHODS: In the present work the prevalence of 54 different HPV types
      and 18 other sexually transmitted infection as well as the predominant risk
      factors for the development of cervical cancer were investigated in Ouagadougou.
      A cross-sectional study on two populations without (n=471) and with known
      cervical dysplasia (n=39) was carried out between October 2013 and March 2014.
      Retrospectively, data on possible and secured risk factors of the cervical
      carcinoma were collected. The participants were examined gynecologically and a
      vaginal lavage was taken, which was molecular genetically examined for 54
      different human papillomavirus genotypes and 18 other STIs. RESULTS: The
      prevalence of human papillomavirus was 42.3% (188/444) in the first study
      population and 87.2% (34/39) in the second study population. The immunization
      coverage would be 24.5% of the HPV types and 33.9% of the high-risk HPV types
      with quadrivalent vaccine Gardasil(r). The nonavalent vaccine Gardasil(r)9
      (9vHPV) would cover 37.3% of all HPV types and 57.1% of high-risk HPV types.
      CONCLUSION: The prevention of infection with human papillomaviruses by
      vaccination is expected to result in a drastic reduction in the morbidity and
      mortality of the cervical cancer in Burkina Faso.

PMID- 30120546
TI  - Is Myotomy Plus Diverticulopexy Suitable for Symptomatic Zenker's Diverticula?
AB  - The aim of the study was to prospectively evaluate the outcome of myotomy plus
      diverticulopexy over short and long-terms. A prospectively collected consecutive
      series (2007-2017) of 37 patients undergoing myotomy plus diverticulopexy was
      analyzed for clinical condition, operative information, peri-operative events,
      and follow-up by means of interview and physical examination. Diverticulopexy was
      scheduled regardless of the diverticulum's features and patient condition, other
      than operability. There was no choice or selection between possible treatment
      options. Patients were evaluated pre-operatively, at post-operative day 30 and
      after 1 year. Follow-up aimed at assessing the subjective condition following
      treatment. During the interview, patients were asked to self-assess their ability
      to swallow before and after surgery. No patient had peri-operative events,
      complications associated with the procedure, wound infection or impaired
      swallowing. All patients could start drinking the day after operation, could
      return to solid diet on post-operative day 2 and be discharged on post-operative
      days 3-4. Barium swallowing was not necessary before discharge. Full solid diet
      was resumed according to patient's compliance from post-operative day 2 (some
      patients refused solid diet soon after the operation even if asymptomatic).
      Follow-up ranged between 1 and 8 years. No patient was lost at follow-up. No
      disease recurrence was observed. Finally, no patient needed or sought for a
      clinical examination between the follow-up calls. Patients reported at least 50%
      improvement of symptomatology after 1 year. Diverticulopexy appears to be
      clinically safe, methodologically reproducible, and an effective procedure; it
      avoids suturing and offers good outcome results along with high patient
      satisfaction.

PMID- 30120548
TI  - Tree growth and water-use in hyper-arid Acacia occurs during the hottest and
      driest season.
AB  - Drought-induced tree mortality has been recently increasing and is expected to
      increase further under warming climate. Conversely, tree species that survive
      under arid conditions might provide vital information on successful drought
      resistance strategies. Although Acacia (Vachellia) species dominate many of the
      globe's deserts, little is known about their growth dynamics and water-use in
      situ. Stem diameter dynamics, leaf phenology, and sap flow were monitored during
      3 consecutive years in five Acacia raddiana trees and five Acacia tortilis trees
      in the Arid Arava Valley, southern Israel (annual precipitation 20-70 mm,
      restricted to October-May). We hypothesized that stem growth and other tree
      activities are synchronized with, and limited to single rainfall or flashflood
      events. Unexpectedly, cambial growth of both Acacia species was arrested during
      the wet season, and occurred during most of the dry season, coinciding with
      maximum daily temperatures as high as 45  degrees C and vapor pressure deficit of
      up to 9 kPa. Summer growth was correlated with peak sap flow in June, with almost
      year-round activity and foliage cover. To the best of our knowledge, these are
      the harshest drought conditions ever documented permitting cambial growth. These
      findings point to the possibility that summer cambial growth in Acacia under
      hyper-arid conditions relies on concurrent leaf gas exchange, which is in turn
      permitted by access to deep soil water. Soil water can support low-density tree
      populations despite heat and drought, as long as recharge is kept above a minimum
      threshold.

PMID- 30120547
TI  - Ecosystem multifunctionality increases with beta diversity in restored prairies.
AB  - The loss of biodiversity at local and larger scales has potentially dramatic
      effects on ecosystem functioning. Many studies have shown that ecosystem
      functioning depends on biodiversity, but the role of beta diversity, spatial
      variation in community composition, is less clear than that of local-scale
      (alpha) diversity. To test the hypothesis that beta diversity would increase
      ecosystem multifunctionality through variation in species functional traits, we
      gathered data on plant community composition, plant functional traits, and seven
      ecosystem functions across 29 restored prairies. We found that averaged
      multifunctionality (mean of seven ecosystem functions) increased with both
      taxonomic beta diversity and functional beta diversity. The abundance of the
      dominant species, big bluestem, played a more minor role, suggesting a limited
      role for the selection effect. Neither taxonomic nor functional alpha richness
      was associated with multifunctionality, though this finding may be sensitive to
      the identity of the functions included because alpha diversity was associated
      with some individual functions in opposing directions. These findings suggest
      that in systems structured largely by natural processes, beta diversity (a
      patchwork of functionally different plant communities) and dominant species
      abundance may be more important than alpha diversity in fostering ecosystem
      multifunctionality. These findings suggest the need for an increased focus on
      community heterogeneity to reestablish functional ecosystems during restoration.

PMID- 30120549
TI  - Is contralateral inguinal exploration necessary in preterm girls undergoing
      inguinal hernia repair during the first months of life?
AB  - BACKGROUND: To assess the need for contralateral surgical exploration in preterm
      girls with symptomatic unilateral inguinal hernia. METHODS: The medical data of
      girls operated for inguinal hernia between 2004 and 2016 in a single pediatric
      surgery center were retrospectively collected. Preterm girls operated for
      unilateral hernia before 6 months of life were selected (55/517 cases) to assess
      the incidence and risk factors for contralateral metachronous inguinal hernia
      (CMIH). RESULTS: CMIH was observed in 7% of cases (4 girls with a right inguinal
      hernia in 3 cases) at a mean age of 4.2 years. Only one case occurred early (3
      months). Birth weight and term were comparable (1674 +/- 620 g and 32 +/- 5 WA
      without CMIH vs. 1694 +/- 582 g and 33 +/- 3 WA with CMIH). CONCLUSION:
      Contralateral inguinal hernia is very rare and generally occurs several years
      after inguinal repair surgery in preterm girls, which should encourage
      practitioners to follow these children throughout childhood for the subsequent
      development of inguinal hernia. This study did not find any arguments in favor of
      systematic contralateral exploration in preterm girls.

PMID- 30120550
TI  - Long-term outcomes and complications after laparoscopic-assisted anorectoplasty
      vs. posterior sagittal anorectoplasty for high- and intermediate-type anorectal
      malformation.
AB  - PURPOSE: Laparoscopic-assisted anorectoplasty (LAARP) is a minimally invasive
      procedure in which the levator ani muscle is left to potentially improve
      postoperative fecal continence. This study aimed to retrospectively evaluate
      postoperative complications and long-term outcomes of fecal continence after
      LAARP and compare them to those after posterior sagittal anorectoplasty (PSARP).
      METHODS: Forty-five male patients with high and intermediate anorectal
      malformation (aged >= 4 years) who underwent LAARP or PSARP (LAARP 29, PSARP 16)
      from 1999 to 2013 were included. Postoperative complications and postoperative
      fecal continence were retrospectively evaluated and compared. Postoperative
      complications were also compared before and after introducing a urethroscope
      during fistula resection. RESULTS: Complications after LAARP and PSARP were seen
      in 12 vs. 2 cases (p = 0.09) of mucosal prolapse and in 9 vs. 1 case (p = 0.07)
      of posterior urethral diverticulum (PUD), respectively. The incidence of PUD
      decreased after introduction of a urethroscopy from 40% in 8/20 cases to 11% in
      1/9 cases. No significant difference was found in terms of fecal continence in
      both groups. CONCLUSION: Through our study, greater improvement of postoperative
      fecal continence after LAARP has not been shown. LAARP was at higher risk for
      mucosal prolapse and PUD. However, precise dissection of the urethral fistula
      could be performed after the introduction of urethroscopy.

PMID- 30120551
TI  - Plant growth-promoting bacteria Kosakonia radicincitans mediate anti-herbivore
      defense in Arabidopsis thaliana.
AB  - MAIN CONCLUSION: This study demonstrates that the application of the PGPB strain,
      Kosakonia radicincitans enhances a plant's resistance against phloem-feeding and
      chewing insects in Arabidopsis thaliana. The plant growth-promoting bacterial
      strain K. radicincitans DSM 16656 applied to A. thaliana reduced the number of
      phloem-feeding insects of both the specialist Brevicoryne brassicae and the
      generalist Myzus persicae. While weight gain of the generalist chewing insect
      Spodoptera exigua was reduced by 30% on A. thaliana plants treated with K.
      radicincitans, growth of the specialist caterpillar Pieris brassicae was not
      affected when compared with caterpillars from control plants. Since generalist
      and specialist chewing insects responded differentially to PGPB application, the
      implication of signaling pathways in PGPB mediated changes in plant defense was
      studied using two signaling pathway mutants impaired in their salicylic acid
      (npr1-1 mutant) or jasmonic acid (coi1-1 mutant) pathway. We found that the
      jasmonic acid pathway is relevant for upregulation of aliphatic glucosinolates
      and suppression of the chewing generalist S. exigua larval growth. Chewing from
      generalist P. brassicae increased glucosinolate content in A. thaliana leaves
      mediated via both signaling pathways. However, only in the npr1-1 mutant, which
      contains the highest aliphatic glucosinolate content, the P. brassicae induced
      further enrichment of glucosinolates, resulting in a reduction of larval growth.
      Effects of K. radicincitans on plant resistance could not be explained by changes
      in glucosinolate contents or composition. Our results demonstrate the distinct
      role played by K. radicincitans in suppressing insect performance in A. thaliana.

PMID- 30120552
TI  - ColorEM: analytical electron microscopy for element-guided identification and
      imaging of the building blocks of life.
AB  - Nanometer-scale identification of multiple targets is crucial to understand how
      biomolecules regulate life. Markers, or probes, of specific biomolecules help to
      visualize and to identify. Electron microscopy (EM), the highest resolution
      imaging modality, provides ultrastructural information where several subcellular
      structures can be readily identified. For precise tagging of (macro)molecules,
      electron-dense probes, distinguishable in gray-scale EM, are being used. However,
      practically these genetically-encoded or immune-targeted probes are limited to
      three targets. In correlated microscopy, fluorescent signals are overlaid on the
      EM image, but typically without the nanometer-scale resolution and limited to
      visualization of few targets. Recently, analytical methods have become more
      sensitive, which has led to a renewed interest to explore these for imaging of
      elements and molecules in cells and tissues in EM. Here, we present the current
      state of nanoscale imaging of cells and tissues using energy dispersive X-ray
      analysis (EDX), electron energy loss spectroscopy (EELS), cathodoluminescence
      (CL), and touch upon secondary ion mass spectroscopy at the nanoscale (NanoSIMS).
      ColorEM is the term encompassing these analytical techniques the results of which
      are then displayed as false-color at the EM scale. We highlight how ColorEM will
      become a strong analytical nano-imaging tool in life science microscopy.

PMID- 30120553
TI  - Establishing the cognitive signature of human brain networks derived from
      structural and functional connectivity.
AB  - Numerous neuroimaging studies have identified various brain networks using task
      free analyses. While these networks undoubtedly support higher cognition, their
      precise functional characteristics are rarely probed directly. The frontal,
      temporal, and parietal lobes contain the majority of the tertiary association
      cortex, which are key substrates for higher cognition including executive
      function, language, memory, and attention. Accordingly, we established the
      cognitive signature of a set of contrastive brain networks on the main tertiary
      association cortices, identified in two task-independent datasets. Using graph
      theory analysis, we revealed multiple networks across the frontal, temporal, and
      parietal cortex, derived from structural and functional connectivity. The
      patterns of network activity were then investigated using three task-active fMRI
      datasets to generate the functional profiles of the identified networks. We
      employed representational dissimilarity analysis on these functional data to
      quantify and compare the representational characteristics of the networks. Our
      results demonstrated that the topology of the task-independent networks was
      strongly associated with the patterns of network activity in the task-active
      fMRI. Our findings establish a direct relationship between the brain networks
      identified from task-free datasets and higher cognitive functions including
      cognitive control, language, memory, visuospatial function, and perception. Not
      only does this study support the widely held view that higher cognitive functions
      are supported by widespread, distributed cortical networks, but also it
      elucidates a methodological approach for formally establishing their
      relationship.

PMID- 30120554
TI  - Necrotizing fasciitis of the head and neck: our experience with vacuum-assisted
      closure therapy.
AB  - OBJECTIVES: To present the outcomes of our case series of head and neck
      necrotizing fasciitis (HNNF) in which vacuum-assisted closure (VAC) is used in
      most of the cases in the treatment. METHODS: Case series in a tertiary referral
      center. RESULTS: Eleven patients were treated for HNNF between January 2008 and
      January 2017. Patients were two females and nine males, the mean age was 57.1.
      Oral cavity and tracheotomy/tracheostomy sites were the main aetiological foci of
      the infection. Three patients were treated with aggressive debridements and
      conventional dressing, whereas eight patients were treated with incision and
      exploration followed by limited skin excisions and VAC dressing. The mean number
      of surgical debridements was 2.3. The mean length of hospital stay was 41.8 days.
      Complications were observed in all patients except one. The mortality rate of
      HNNF in our series was 18%. The cause of death was severe sepsis and multi-organ
      failure in one case and mediastinitis followed by respiratory distress syndrome
      in the other case. CONCLUSION: HNNF is still a mortal disease and surgical
      debridements are crucial. The current study is the only case series in the
      literature in which VAC treatment was used in consecutive cases of HNNF. VAC
      treatment can play a major role in the post-operative care of HNNF patients. It
      reduces the amount of excised skin during debridements and stimulates wound
      healing. VAC treatment may be included in the treatment protocol of HNNF
      alongside surgical debridements and medical therapy.

PMID- 30120556
TI  - Safety of oral hydration after cisplatin infusion in an outpatient lung cancer
      unit.
AB  - PURPOSE: Hydration is needed before and after cisplatin infusion for reducing the
      risk of nephrotoxicity. Even though there is no standard regimen, patients
      receive mostly intravenous hydration before and after cisplatin leading
      hospitalization during at least one night. Since the feasibility has been
      published, oral hydration after cisplatin was implemented in our practice. The
      safety of this new way of hydration needs to be assessed in clinical practice.
      METHODS: We collected medical records from patients treated by cisplatin for lung
      cancer in our unit between 2010 and 2016. We retrospectively analyzed the
      incidence of cisplatin induced nephrotoxicity between after and before the change
      of hydration regimen. RESULTS: Our patient cohort included 241 patients hydrated
      by intravenous regimen (IV/IV group) and 276 patient hydrated by intravenous and
      oral regimen (IV/PO group). Grade >= 1 nephrotoxicity occurred in 39.4 and 25.7%
      in the IV/IV and IV/PO groups respectively (p = 0.001). Age over 70 at baseline
      was a predictive factor for nephrotoxicity, but not estimated glomerular
      filtration rate nor cisplatin-associated drugs. After a multivariate analysis,
      age remained a predictive factor for nephrotoxicity and IV/PO hydration
      associated with a decrease in nephrotoxic risk. CONCLUSION: The implementation of
      oral hydration in our practice was not associated with an increase in
      nephrotoxicity. Our observation based on large data from clinical practice shows
      that oral hydration after cisplatin is safe.

PMID- 30120557
TI  - Stability of symptom clusters and sentinel symptoms during the first two cycles
      of adjuvant chemotherapy.
AB  - PURPOSE: Ascertaining the stability of symptom clusters and identifying sentinel
      symptoms have been top priorities in symptom cluster research. Identifying
      sentinel symptoms would help to determine the underlying mechanisms of symptom
      clusters and facilitate effective symptom management. This study aimed to
      evaluate the stability of symptom clusters during the 1st and 2nd cycles of
      adjuvant chemotherapy (CTx) and to identify sentinel symptoms. METHODS: This is a
      secondary data analysis of data from the Paradigm Shift in Chemotherapy-Induced
      Nausea and Vomiting (PS-CINV) study. Data utilized were from cancer patients who
      received adjuvant chemotherapy and completed symptom evaluation in the 1st and
      2nd cycles (N = 209). The severity of 20 symptoms was evaluated on a 0-to-10
      numeric rating scale. Principal component and hierarchical cluster analyses
      identified symptom clusters, and principal variable analysis identified sentinel
      symptoms. RESULTS: Among 20 symptoms, 13 symptoms formed 4 symptom clusters in
      the 1st cycle: a physical-psychological (pain, dyspnea, sleep disturbance,
      anxiety, depression), a gastrointestinal (nausea, loss of appetite, taste
      change), a fatigue-cognitive (fatigue, difficulty concentrating, drowsiness), and
      a urosexual (urinary problem, sexual problem) symptom cluster. During the 2nd
      cycle, stable symptom clusters were identified, with merging of the physical
      psychological and fatigue-cognitive symptom clusters, resulting in three
      clusters. Sentinel symptoms were identified in the following order: anxiety, loss
      of appetite and fatigue (1st cycle) and loss of appetite, depression, and fatigue
      (2nd cycle). CONCLUSION: Symptom clusters demonstrated phase-specific stability.
      The current study identified a core set of symptoms that form stable symptom
      clusters during the 1st and 2nd cycles of CTx. Principal variable analysis
      identified sentinel symptoms which could facilitate efficient symptom management.

PMID- 30120558
TI  - Computational analysis on the feasibility of transverse iliosacral screw fixation
      for different sacral segments.
AB  - PURPOSE: To evaluate the feasibility of transverse iliosacral (TIS) screw
      placement in different segments of the sacrum and measure the parameters of the
      unilateral iliosacral (IS) screw in the case that cannot be inserted the TIS
      screw. METHODS: This study used 100 pelvic continuous computed tomography images.
      Mimics (Materialise Interactive Medical Image Control System) was used to
      reconstruct the three-dimensional pelvis model. All sacrums were divided into the
      normal group and dysmorphic group. Any difference in osseous fixation pathway
      (OFP) diameter in the first two segments between both groups was investigated. In
      dysmorphic sacrums, the optimal inserting angle and length of the unilateral S1
      screw were measured. The number of foramen in every sacrum was recorded. RESULTS:
      Thirty-two sacrums had sacral dysmorphism. The OFP diameter for the S2 TIS screw
      in the dysmorphic group was larger than that in the normal group (p = 0.02).
      Receiver operating characteristic curve analysis indicated the cutoff values as
      20.55 mm and 15.18 degrees  for the S1 front edge height and S1S2 angle,
      respectively. In the dysmorphic case, the unilateral S1 IS screw should be
      inserted with a cephalad incline angle of 36.14 +/- 5.97 degrees  and a ventrally
      incline angle of 37.33 +/- 4.64 degrees . S3 TIS screw placement rate was 53.1%
      in the dysmorphic group. CONCLUSIONS: The most common cause of sacral dysmorphism
      is the fusion of the L5 to the true S1. In dysmorphic sacrums, the unilateral IS
      screw should be placed obliquely in the S1 segment, and the S2 segment usually
      has a sufficient OFP for the TIS screw. Using S3 TIS screw and two TIS screws in
      the first segment technique is not recommended because of a high risk.

PMID- 30120559
TI  - Correction to: Effectiveness of Rotigotine plus intensive and goal-based
      rehabilitation versus Rotigotine alone in "de-novo" Parkinsonian subjects: a
      randomized controlled trial with 18-month follow-up.
AB  - The original version of this article unfortunately contained a mistake. The
      funding information was incorrect. The corrected funding information is given
      below.

PMID- 30120560
TI  - Cluster headache: pathophysiology, diagnosis and treatment.
AB  - Cluster headache (CH) is characterized by attacks of severe, strictly unilateral
      pain that is orbital, supraorbital, temporal, or any combination of these, lasts
      15-180 min, and occurs from once every other day to eight times a day. The pain
      is associated with ipsilateral conjunctival injection, lacrimation, nasal
      congestion, rhinorrhea, forehead and facial sweating, miosis, ptosis and/or
      eyelid edema, and/or with restlessness or agitation. The understanding of the
      pathophysiological mechanisms behind CH is far from complete, but CH is
      considered to be a neurovascular and chronobiologic headache disorder, with a
      pivotal role played by the central brain mechanisms. The diagnosis of CH is based
      on a careful history that elicits the clinical features of attacks, ipsilateral
      autonomic phenomena, and the cyclical nature of the bouts in which the attacks
      occur. Additional diagnostic interventions are needed to rule out secondary
      causes of CH. The main focus of therapy is to abort attacks once they have begun
      and to prevent future attacks. Alternative interventions in patients with CH who
      have not experienced any meaningful benefit from preventive drugs are well
      defined. Although there have been advances in the diagnosis and therapy of CH, a
      significant number of CH patients experience misdiagnoses and diagnostic delay,
      which stalls the possibility of the timely application of adequate abortive and
      preventive therapy.

PMID- 30120555
TI  - Catalase and nonalcoholic fatty liver disease.
AB  - Obesity and insulin resistance are considered the main causes of nonalcoholic
      fatty liver disease (NAFLD), and oxidative stress accelerates the progression of
      NAFLD. Free fatty acids, which are elevated in the liver by obesity or insulin
      resistance, lead to incomplete oxidation in the mitochondria, peroxisomes, and
      microsomes, leading to the production of reactive oxygen species (ROS). Among the
      ROS generated, H2O2 is mainly produced in peroxisomes and decomposed by catalase.
      However, when the H2O2 concentration increases because of decreased expression or
      activity of catalase, it migrates to cytosol and other organelles, causing cell
      injury and participating in the Fenton reaction, resulting in serious oxidative
      stress. To date, numerous studies have been shown to inhibit the pathogenesis of
      NAFLD, but treatment for this disease mainly depends on weight loss and exercise.
      Various molecules such as vitamin E, metformin, liraglutide, and resveratrol have
      been proposed as therapeutic agents, but further verification of the dose
      setting, clinical application, and side effects is needed. Reducing oxidative
      stress may be a fundamental method for improving not only the progression of
      NAFLD but also obesity and insulin resistance. However, the relationship between
      NAFLD progression and antioxidants, particularly catalase, which is most commonly
      expressed in the liver, remains unclear. Therefore, this review summarizes the
      role of catalase, focusing on its potential therapeutic effects in NAFLD
      progression.

PMID- 30120562
TI  - Windmill nystagmus in a patient with subacute visual loss.

PMID- 30120563
TI  - Magnetic resonance imaging in Alzheimer's disease and mild cognitive impairment.
AB  - Research utilizing magnetic resonance imaging (MRI) has been crucial to the
      understanding of the neuropathological mechanisms behind and clinical
      identification of Alzheimer's disease (AD) and mild cognitive impairment (MCI).
      MRI modalities show patterns of brain damage that discriminate AD from other
      brain illnesses and brain abnormalities that are associated with risk of
      conversion to AD from MCI and other behavioural outcomes. This review discusses
      the application of various MRI techniques to and their clinical usefulness in AD
      and MCI. MRI modalities covered include structural MRI, diffusion tensor imaging
      (DTI), arterial spin labelling (ASL), magnetic resonance spectroscopy (MRS), and
      functional MRI (fMRI). There is much evidence supporting the validity of MRI as a
      biomarker for these disorders; however, only traditional structural imaging is
      currently recommended for routine use in clinical settings. Future research is
      needed to warrant the inclusion for more advanced MRI methodology in forthcoming
      revisions to diagnostic criteria for AD and MCI.

PMID- 30120564
TI  - Ars comparandi: "molecular convergence" versus "functional homology".

PMID- 30120565
TI  - Changes in the properties of calcium-carbon inclusions during leaf development
      and their possible relationship with leaf functional maturation in three
      inclusion-bearing species.
AB  - In many plant species, carbon-calcium inclusion (calcium oxalate crystals or
      cystoliths containing calcium carbonate) formation is a fundamental part of their
      physiology even necessary for normal growth and development. Despite the long
      standing studies on carbon-calcium inclusions, the alterations in their
      properties during leaf development and their possible association with the
      maturation of the photosynthetic machinery have not been previously examined. In
      order to acquire more insights into this subject, we examined three of the most
      common species bearing abundant inclusions of different types, i.e., Amaranthus
      hybridus, Vitis vinifera, and Parietaria judaica. Results of our study showed
      that, irrespective of species and type of inclusion, similar patterns in the
      alterations of their properties are observed during leaf maturation, except for
      some differences in cell differentiation and distribution between raphides and
      druses in Vitis vinifera. As expected, inclusion formation has taken place at
      very early developmental stages and maximum density was observed in very young
      leaves. Inclusion properties are changing in a coordinated way with leaf area and
      these modifications are compatible with the concept that each idioblast or
      lithocyst "services" a finite number/area of adjacent cells. This tight
      coordination is also evident at the whole leaf level. Moreover, we observed an
      association of the properties of carbon-calcium inclusions and gas exchange,
      suggesting a possible implication of these structures in photosynthesis.

PMID- 30120566
TI  - A 3D nanoscale polyhedral oligomeric silsesquioxanes network for microextraction
      of polycyclic aromatic hydrocarbons.
AB  - Polyhedral oligomeric silsesquioxanes are 3D nanoscaled materials with large
      potential in solid phase microextraction (SPME). Here, as a case study, an
      octaglycidyldimethylsilyl modified polyhedral oligomeric silsesquioxane network
      is described. It was deposited on a stainless steel wire via a sol-gel method and
      used as a fiber coating for SPME of aromatic compounds. The uniform pore
      structure, high surface area, and hydrophobicity of the network make it
      susceptible toward isolation of non-polar and semi-polar chemical compounds. The
      performance of the fiber coating was tested with three classes of environmental
      pollutants, viz. chlorobenzenes (CBs), benzenes (benzene, toluene, ethylbenzene,
      xylene; known as BTEX), and polycyclic aromatic hydrocarbons. The effects of
      various types of sol-gel precursors on the fabrication and performance of fiber
      coatings were investigated. The extraction capability of the fiber coating was
      compared with the polydimethyl siloxane/divinylbenzene based commercial fiber.
      Parameters affecting headspace analysis and gas chromatographic quantitation were
      optimized. The method was applied to the quantification of PAHs, as model
      analytes, in tea, coffee and some environmental waters. Linear responses
      typically cover the 1-200 ng.L-1 concentration range, limits of detection are
      between 0.1 and 0.3 ng.L-1, intra-day relative standard deviation are <10%, and
      inter-day RSDs are <12%. The fiber has a long lifespan and can be used >200
      times. Graphical abstract Schematic presentation of a headspace solid phase
      microextraction process which is implemented to the analysis of PAHs in tea and
      coffee samples. The SEM image of the SPME fiber coating, the 3D nanoscale
      polyhedral oligomeric silsesquioxane (POSS) network, and the POSS-epoxy molecular
      structure are shown.

PMID- 30120561
TI  - Moyamoya angiopathy: early postoperative course within 3 months after STA-MCA
      bypass surgery in Europe-a retrospective analysis of 64 procedures.
AB  - BACKGROUND: Despite the consensus on the necessity of revascularizing surgery in
      Moyamoya angiopathy in Asia, the indication in Caucasian Moyamoya patients is
      discussed controversially. OBJECTIVE: The safety of revascularizing surgery in
      Europe should be clarified. METHODS: This study retrospectively analyzed the rate
      of complications as well as clinical symptoms within the first 3 months after
      bypass surgery between superficial temporal artery and middle cerebral artery
      (STA-MCA). RESULTS: 64 direct bypass procedures in 45 patients (95.5% Caucasians)
      were analyzed. The magnetic resonance imaging at day 6 showed subdural hematoma
      in 60.3%. The mean diameter of these hematomas on magnetic resonance imaging was
      5.1 mm (SD 3.4 mm) and increased in 25% at follow-up. No difference was found
      between those patients with early (day 1) or late (day 7) restarts of
      antiplatelet therapy. Magnetic resonance imaging at day 6 revealed hyperperfusion
      syndrome after six of 64 procedures (9.3%). Three of these six had clinical
      symptoms; two-thirds were transient within seconds. Magnetic resonance imaging
      depicted stroke after seven procedures (10.9%). Five of these seven patients had
      no new symptoms. Altogether, after ten procedures (15%), patients complained
      about clinical symptoms. These were all transient. No new transient ischemic
      attacks occurred during the 3 month follow-up and no new lesions were detected in
      magnetic resonance imaging. Only two patients underwent surgery for asymptomatic
      subdural hematoma. All other subdural hematomas resolved spontaneously.
      CONCLUSION: Revasculating surgery is a safe procedure in Caucasian patients with
      Moyamoya angiopathy. The observed complications have a good prognosis.

PMID- 30120568
TI  - Expression of concern: Short hairpin RNA (shRNA) of type 2 interleukin-1 receptor
      (IL1R2) inhibits the proliferation of human osteosarcoma U-2 OS cells.

PMID- 30120567
TI  - Chemical reactivity of the frustrated Lewis pairs in borophosphines: a
      theoretical analysis of their Lewis acidity, Lewis basicity and Fukui function.
AB  - The chemical reactivity of a set of borophosphines of the general formula R2B-G
      PY2, where G is the connector group between the Lewis acidic site, a borane
      group, and the Lewis basic site, a phosphine fragment, is theoretically
      investigated through their Lewis acidity and Lewis basicity, as well as the
      location of the Fukui function and the shape of the molecular electrostatic
      potential. The role of some global reactivity descriptors, like the vertical
      ionization potential, I, and the vertical electron affinity, A, is also analyzed
      in order to gain a deeper insight on the intrinsic chemical reactivity of these
      borophosphines. We also use the energies involved in the formation of the adducts
      between the borophosphine and the ions H- and H+ to estimate the Lewis acidity
      and Lewis basicity, respectively; by their nature, these energies represent local
      reactivity descriptors. Some of these borophosphines are able to activate the
      covalent bond in the hydrogen molecule. Possible paths for the hydrogen release
      reaction from the zwitterion R[Formula: see text]HB-G-PH[Formula: see text] are
      studied using the mentioned quantities, suggesting that an intramolecular hydride
      shift mechanism seems to be more favorable than a proton migration process. The
      acceptor Fukui function f+(r) proved to be useful to identify the acidic
      molecular sites for the interaction with the hydride ion and the relative
      stability of the corresponding adducts is related to the relative values of this
      function.

PMID- 30120569
TI  - Complete genome sequence of PFP1, a novel T7-like Pseudomonas fluorescens
      bacteriophage.
AB  - The complete genomic sequence of Pseudomonas fluorescens bacteriophage PFP1,
      isolated from sewage samples collected in Liaoning Province, China, were
      sequenced in this study and found to be 40,914 bp long. The PFP1 genome is
      composed of linear double-stranded DNA with 55.81% G+C content and 45 putative
      protein-coding genes, and no rRNA and tRNA genes. Comparative genomics and
      phylogenetic analysis revealed that the Pseudomonas fluorescens phage PFP1 is a
      new member of the genus T7virus. This information can be used to develop novel
      phage-based control strategies against Pseudomonas fluorescens.

PMID- 30120570
TI  - Co-Tetraphenylporphyrin (co-TPP) in TM-TPP (TM = Fe, Co, Ni, Cu, and Zn) series:
      a new optical material under DFT.
AB  - A detailed investigation of the structure, electronic, spectroscopic, and optical
      properties of a series of transition metal-doped tetraphenylporphyrins (TM-TPP;
      TM = Fe, Co, Ni, Cu and Zn) is performed under density functional framework. The
      structure and stability of tetraphenylporphyrin (TPP) and TM-TPPs are understood
      with HOMO-LUMO gap, chemical hardness, and binding energies of the transition
      metals to the compound. Optical properties of TPP and TM-TPP series are assessed
      with relevant optical absorption spectra. A couple of visible active compounds,
      viz. Co-TPP and Ni-TPP, are reported for the first time for future opto
      electronic applications. To gain insight on the possible synthesis of these
      compounds, we have analyzed frontier molecular orbitals (FMOs) as well as infra
      red spectra. Graphical abstract Optical absorption spectra of TPP and TM-TPPs,
      and infrared spectra of TPP merged with Co-TPP.

PMID- 30120572
TI  - Correction to: Canada: will privacy rules continue to favour open science?
AB  - This article was inadvertently published under a draft title.

PMID- 30120571
TI  - Cellulose exopolysaccharide from sugarcane molasses as a suitable substrate for
      2D and 3D neuron and astrocyte primary cultures.
AB  - Bacteria-synthesized polysaccharides have attracted interest for biomedical
      applications as promising biomaterials to be used as implants and scaffolds. The
      present study tested the hypothesis that cellulose exopolysaccharide (CEC)
      produced from sugarcane molasses of low cost and adequate purity would be
      suitable as a template for 2D and 3D neuron and/or astrocyte primary cultures,
      considering its low toxicity. CEC biocompatibility in these primary cultures was
      evaluated with respect to cell viability, adhesion, growth and cell function
      (calcium imaging). Polystyrene or Matrigel(r) matrix were used as comparative
      controls. We demonstrated that the properties of this CEC in the 2D or 3D
      configurations are suitable for differentiation of cortical astrocytes and
      neurons in single or mixed cultures. No toxicity was detected in neurons that
      showed NMDA-induced Ca2+ influx. Unlike other polysaccharides of bacterial
      synthesis, the CEC was efficient as a support even in the absence of surface
      conjugation with extracellular matrix proteins, maintaining physiological
      characteristics of cultured neural cells. These observations open up the
      perspective for development of a novel 3D biofunctional scaffold produced from
      bacterial cellulose and obtained from renewable sources whose residues are not
      pollutants. Its low cost and possibility to be manufactured in scale are also
      suitable for potential applications in regenerative medicine.

PMID- 30120573
TI  - Conclusion: harmonisation in genomic and health data sharing for research: an
      impossible dream?
AB  - There are clear benefits from genomics and health data sharing in research and in
      therapy for individuals across societies. At the same time, citizens have
      different expectations and fears about that data sharing. International
      legislation in relation with research ethics and practice and, particularly, data
      protection create a particular environment that, as is seen in the articles in
      part two of this special issue, are crying out for harmonisation both at a
      procedural but at fundamental conceptual levels. The law of data sharing is
      pulling in different directions. This paper poses the question, 'harmonisation,
      an impossible dream?' and the answer is a qualified 'no'. The paper reflects on
      what can be seen in the papers in part two of the special issue. It then
      identifies three major areas of conceptual uncertainty in the new EU General Data
      Protection Regulation (not because it has superiority over other jurisdictions,
      but because it is a recent revision of data protection law that leaves universal
      conceptual questions unclear). Thereafter, the potential for Artificial
      Intelligence to meet some of the shortcomings is discussed. The paper ends with a
      consideration of the conditions under which data sharing harmonisation might be
      achieved: an understanding of a human rights approach and citizen sensitivities
      in considering the 'public interest'; social liberalism as a basis of solidarity;
      and the profession of 'researcher'.

PMID- 30120574
TI  - Correction to: China: concurring regulation of cross-border genomic data sharing
      for statist control and individual protection.
AB  - The article China: concurring regulation of cross-border genomic data sharing for
      statist control and individual protection, written by Yongxi Chen and Lingqiao
      Song, was originally published electronically on the publisher's internet portal
      (currently SpringerLink) on 16 July 2018 without open access. With the author(s)'
      decision to opt for Open Choice the copyright of the article changed on 16 August
      2018 to

PMID- 30120575
TI  - A hollow microporous organic network as a fiber coating for solid-phase
      microextraction of short-chain chlorinated hydrocarbons.
AB  - A solid-phase microextraction (SPME) fiber coated with a hollow microporous
      organic network (H-MON) was fabricated for the analysis of short-chain
      chlorinated paraffins (SCCPs). The sorbent was prepared by reacting tetra(4
      ethynylphenyl)methane and 1,4-diiodobenzene using bis-(triphenylphosphine)
      palladium(II) as the catalyst in the presence of silica sphere templates, which
      then were removed by hydrofluoric acid. The SCCPs were quantified by GC-MS
      working in the negative chemical ionization mode. The H-MON has a high specific
      surface (701 m2.g-1) and microporosity (pore size <2 nm). Extraction temperature,
      extraction time, and ionic strength of the sample solutions were optimized by
      using the Box-Behnken design. The head-space SPME exhibits better extraction
      performance than the direct immersion mode. Under optimal working conditions, the
      detection limit (3 times of the standard deviation) is 0.03 ng.mL-1 in the water
      samples. Response is linear in the 0.05-10 ng.mL-1 concentration range.
      Repeatability and reproducibility, expressed as the relative standard deviations,
      ranged from 4.6 to 11.0%. The method was successfully applied in the analysis of
      SCCPs in water, sediments, organisms, and atmospheric particulate matter samples.
      Graphical abstract Schematic of the fabrication of a hollow microporous organic
      network (H-MON) on stainless steel fibers for use in SPME. The method was applied
      to the determination of short-chain chlorinated paraffins in biological,
      environmental water and atmospheric particulate matter (PM2.5) samples.

PMID- 30120576
TI  - PLGA film/Titanium nanotubues as a sustained growth factor releasing system for
      dental implants.
AB  - Ti-based implants sometimes fail to integrate with surrounding bone tissue due to
      insufficiency of new bone formation and surface bonding. To overcome this
      problem, this research focused on establishing a sustained bone growth factor
      delivery system by applying anodized TiO2 nanotube arrays and PLGA film on the
      titanium implant surface. TiO2 nanotube arrays were made by anodic oxidation
      method, and were then filled with rhBMP2 by vacuum freeze-drying. Next, PLGA was
      deposition on the surface of this material. The designed system was
      characterized, pharmacokinetic release rate of rhBMP2 was determined. Adhesion,
      proliferation, and differentiation activity of osteoblasts cultured on the new
      surfaces and traditional titanium surfaced were compared. SEM showed that a
      surface of TiO2 nanotube arrays were successfully generated. PLGA membranes of 50
      nm, 250 nm, 800 nm thickness were successfully deposited on the surfaces of TiO2
      nanotube layers by using 1%, 3%, 10% PLGA solutions. PLGA film of 250 nm
      thickness showed ideally controlled release of rhBMP2, lasting for 4 weeks.
      Furthermore, 250 nm thickness PLGA film improved osteoblast adhesion,
      proliferation, and levels of alkaline phosphatase. In conclusion, the PLGA film /
      TiO2 nanotube growth factor delivery system can effectively sustain the release
      of rhBMP-2, and promote proliferation and differentiation of MC3T3-E1
      osteoblasts.

PMID- 30120577
TI  - Fabrication and characterization of gold nanoparticle-doped electrospun
      PCL/chitosan nanofibrous scaffolds for nerve tissue engineering.
AB  - In the field of nerve tissue engineering, nanofibrous scaffolds could be a
      promising candidate when they are incorporated with electrical cues. Unique
      physico-chemical properties of gold nanoparticles (AuNPs) make them an
      appropriate component for increasing the conductivity of scaffolds to enhance the
      electrical signal transfer between neural cells. The aim of this study was
      fabrication of AuNPs-doped nanofibrous scaffolds for peripheral nerve tissue
      engineering. Polycaprolactone (PCL)/chitosan mixtures with different
      concentrations of chitosan (0.5, 1 and 1.5) were electrospun to obtain
      nanofibrous scaffolds. AuNPs were synthesized by the reduction of HAuCl4 using
      chitosan as a reducing/stabilizing agent. A uniform distribution of AuNPs with
      spherical shape was achieved throughout the PCL/chitosan matrix. The UV-Vis
      spectrum revealed that the amount of gold ions absorbed by nanofibrous scaffolds
      is in direct relationship with their chitosan content. Evaluation of electrical
      property showed that inclusion of AuNPs significantly enhanced the conductivity
      of scaffolds. Finally, after 5 days of culture, biological response of Schwann
      cells on the AuNPs-doped scaffolds was superior to that on as-prepared scaffolds
      in terms of improved cell attachment and higher proliferation. It can be
      concluded that the prepared AuNPs-doped scaffolds can be used to promote
      peripheral nerve regeneration.

PMID- 30120581
TI  - Correction to: Evaluation of 22G fine-needle aspiration (FNA) versus fine-needle
      biopsy (FNB) for endoscopic ultrasound-guided sampling of pancreatic lesions: a
      prospective comparison study.
AB  - The HTML version of this article was updated to indicate that the copyright is
      with The Author(s).

PMID- 30120580
TI  - Electrospun polylactic acid-chitosan composite: a bio-based alternative for
      inorganic composites for advanced application.
AB  - Fabricating novel materials for biomedical applications mostly require the use of
      biodegradable materials. In this work biodegradable materials like polylactic
      acid (PLA) and chitosan (CHS) were used for designing electrospun mats. This work
      reports the physical and chemical characterization of the PLA-CHS composite,
      prepared by the electrospinning technique using a mixed solvent system. The
      addition of chitosan into PLA, offered decrease in fiber diameter in the
      composites with uniformity in the distribution of fibers with an optimum at
      0.4wt% CHS. The fiber formation and the reduction in fiber diameter were
      confirmed by the SEM micrograph. The inverse gas chromatography and contact angle
      measurements supported the increase of hydrophobicity of the composite membrane
      with increase of filler concentration. The weak interaction between PLA and
      chitosan was confirmed by Fourier transform infrared spectroscopy and thermal
      analysis. The stability of the composite was established by zeta potential
      measurements. Cytotoxicity studies of the membranes were also carried out and
      found that up to 0.6% CHS the composite material was noncytotoxic. The current
      findings are very important for the design and development of new materials based
      on polylactic acid-chitosan composites for environmental and biomedical
      applications.

PMID- 30120579
TI  - Emerging Role of AMPK in Brown and Beige Adipose Tissue (BAT): Implications for
      Obesity, Insulin Resistance, and Type 2 Diabetes.
AB  - PURPOSE OF REVIEW: The global prevalence of type 2 diabetes (T2D) is escalating
      at alarming rates, demanding the development of additional classes of
      therapeutics to further reduce the burden of disease. Recent studies have
      indicated that increasing the metabolic activity of brown and beige adipose
      tissue may represent a novel means to reduce circulating glucose and lipids in
      people with T2D. The AMP-activated protein kinase (AMPK) is a cellular energy
      sensor that has recently been demonstrated to be important in potentially
      regulating the metabolic activity of brown and beige adipose tissue. The goal of
      this review is to summarize recent work describing the role of AMPK in brown and
      beige adipose tissue, focusing on its role in adipogenesis and non-shivering
      thermogenesis. RECENT FINDINGS: Ablation of AMPK in mouse adipocytes results in
      cold intolerance, a reduction in non-shivering thermogenesis in brown adipose
      tissue (BAT), and the development of non-alcoholic fatty liver disease (NAFLD)
      and insulin resistance; effects associated with a defect in mitochondrial
      specific autophagy (mitophagy) within BAT. The effects of a beta3-adrenergic
      agonist on the induction of BAT thermogenesis and the browning of white adipose
      tissue (WAT) are also blunted in mice lacking adipose tissue AMPK. A specific
      AMPK activator, A-769662, also results in the activation of BAT and the browning
      of WAT, effects which may involve demethylation of the PR domain containing 16
      (Prdm16) promoter region, which is important for BAT development. AMPK plays an
      important role in the development and maintenance of brown and beige adipose
      tissue. Adipose tissue AMPK is reduced in people with insulin resistance,
      consistent with findings that mice lacking adipocyte AMPK develop greater NAFLD
      and insulin resistance. These data suggest that pharmacologically targeting
      adipose tissue AMPK may represent a promising strategy to enhance energy
      expenditure and reduce circulating glucose and lipids, which may be effective for
      the treatment of NAFLD and T2D.

PMID- 30120582
TI  - How accurate is preoperative colonoscopic localization of colonic neoplasia?
AB  - INTRODUCTION: Preoperative colonoscopic localization for resection of colonic
      neoplasia, with or without tattooing for guidance, has been extensively used with
      variable accuracy. Difficulty in intraoperative identification of the lesion may
      lead to resection of an incorrect segment or to a more extensive resection than
      originally planned. The aim of this study was to evaluate the accuracy of
      preoperative colonoscopy in determining the site of the lesion. METHODS: A
      prospectively collected IRB-approved institutional database was retrospectively
      queried for all consecutive patients who underwent an elective colon resection
      for neoplasia between 2013 and 2016. Excluded were patients without preoperative
      colonoscopy reports available for comparison or who underwent emergency surgery.
      Surgical plan based on preoperative colonoscopic localization with or without
      tattooing was compared to the final surgery and pathology reports. RESULTS: 203
      patients were included [mean age 68 (35-92) years; 102 males (50.2%)].
      Preoperative colonoscopy was inaccurate in 16.7% (34 patients) leading to a
      change in the surgical plan. Patients with transverse or distal lesions were more
      likely to have a change in final surgical management compared to proximal sided
      lesions (29.7% vs. 3.9%, respectively; p < 0.001). Only 3.8% of the tattooed
      lesions could not be identified during surgery. Additional intraoperative
      colonoscopy was needed in 11 patients (5.5%) to verify exact lesion location.
      Average length of the resected segment was longer in patients who required a
      change in surgical plan (26.44 cm vs. 22.47 cm; p = 0.02). CONCLUSION: Inaccurate
      preoperative colonoscopic localization led to a change in surgical management in
      16.7% of cases, especially in transverse or left sided lesions. Surgeons should
      consider these findings when planning colonic resections.

PMID- 30120583
TI  - Outcomes of pure laparoscopic Glissonian pedicle approach hepatectomy for
      hepatocellular carcinoma: a propensity score matching analysis.
AB  - BACKGROUND: Few studies had been performed to concern the outcomes of pure
      laparoscopic Glissonian pedicle approach hepatectomy (LGAH) for hepatocellular
      carcinoma (HCC). The aim of this study was to compare the outcomes of LGAH versus
      open Glissonian pedicle approach hepatectomy (OGAH) for HCC, especially in
      patients with cirrhosis. METHODS: Hepatocellular carcinoma patients who underwent
      pure LGAH and OGAH between January 2015 and July 2017 in our institution were
      retrospectively enrolled in this study. Propensity score matching (PSM) of
      patients in a ratio of 1:1 was conducted to adjust the known confounders. The
      perioperative and oncological outcomes were compared between the two groups after
      PSM. RESULTS: Some 80 patients underwent pure LGAH and 134 had OGAH. After PSM,
      67 patients in each group were well matched for analysis. Both the postoperative
      overall complication rates (13.4% vs. 29.9%, P = 0.021) and mean comprehensive
      complication index (2.63 vs. 7.40, P = 0.035) were significantly lower in the
      LGAH group than those in OGAH group. Although the operative time was longer in
      the LRH group (P < 0.001), the length of postoperative hospital stay was shorter
      in the LRH group (P = 0.024). Furthermore, both the 3-year overall survival rate
      (73.3% for LGAH vs. 77.8% for OGAH, P = 0.338) and 3-year disease-free survival
      rate (56.4% for LGAH vs. 62.5% for OGAH, P = 0.455) were not significantly
      different between the groups. CONCLUSION: Pure laparoscopic Glissonian approach
      may be a better alternative to open Glissonian approach in selected HCC patients,
      which provided fewer complications, shorter postoperative hospital stay and
      comparable oncological outcomes.

PMID- 30120578
TI  - The Epidemiology of Sleep and Diabetes.
AB  - PURPOSE OF REVIEW: To provide an overview of the mechanistic and epidemiologic
      evidence linking sleep-related exposures, such as short sleep duration,
      obstructive sleep apnea, shift work, and insomnia, with type 2 diabetes risk in
      adults. RECENT FINDINGS: Both poor sleep habits and sleep disorders are highly
      prevalent among adults with type 2 diabetes. In observational studies, short
      sleep duration, obstructive sleep apnea, shift work, and insomnia are all
      associated with higher risk of incident type 2 diabetes and may predict worse
      outcomes in those with existing diabetes. However, interventional studies
      addressing sleep abnormalities in populations with or at high risk for type 2
      diabetes are scarce. Although common sleep abnormalities are associated with risk
      of incident type 2 diabetes and worse prognosis in those with established
      diabetes, there are few randomized trials evaluating the impact of sleep-focused
      interventions on diabetes, making it difficult to determine whether the
      relationship is causal.

PMID- 30120584
TI  - An ERAS protocol for bariatric surgery: is it safe to discharge on post-operative
      day 1?
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy is the most commonly performed
      bariatric surgery in the world. Enhanced recovery after surgery (ERAS) protocols
      have been shown to reduce complications and decrease length of stay for various
      types of surgeries. In this study, we propose an ERAS protocol for laparoscopic
      sleeve gastrectomy and compare the clinical outcomes with patients who received
      standard care. METHODS: We performed a single-institution retrospective analysis
      in patients who underwent laparoscopic sleeve gastrectomy from February 2015 to
      December 2017. Patients were stratified into standard care and ERAS protocol
      groups. The ERAS protocol consisted of goal-directed patient education, specific
      pre- and post-op multi-modal medication regimen, early ambulation, and early oral
      intake. Patients were discharged on their first post-operative day if they met
      appropriate post-surgical milestones. The primary outcomes were length of stay, 7
      and 30-day readmission rates, and complication rates. Secondary outcomes
      included anti-emetic and pain medication utilization, post-operative emesis
      episodes per day, post-operative pain scores, and mortality. RESULTS: We included
      214 consecutive patients who underwent sleeve gastrectomy, 130 were in the ERAS
      group and 84 were in the standard care group. Median hospital stay was
      significantly shorter in the ERAS group compared to the standard care group (1
      vs. 2 days; p < 0.001). There were no differences in 7- or 30-day readmission
      rates (1.5 vs. 1.2%; p = 0.838, 2.3 vs. 2.4%; p = 0.966) or post-operative
      complications (6.2 vs. 3.6%; p = 0.410). The ERAS group also had decreased median
      intra-operative opioid consumption and self-reported pain scores on post
      operative day 1 (27.5 MME vs. 27.4 MME; p = 0.044, 3.3 vs. 3.9; p = 0.046).
      Mortality rate was 0% overall. CONCLUSION: A cost-effective ERAS protocol for
      laparoscopic sleeve gastrectomy results in shorter length of stay, without
      increase in peri-operative morbidity or readmission rates.

PMID- 30120586
TI  - A 3-dimensional C/CeO2 hollow nanostructure framework as a peroxidase mimetic,
      and its application to the colorimetric determination of hydrogen peroxide.
AB  - Various 3-dimensional C/CeO2 hollow nanostructure frameworks (3D C/CeO2 HNFs)
      were synthesized by using a polymer blowing process that is accelerated by adding
      a certain amount of cerium nitrate. Polyvinylpyrrolidone was used as the polymer.
      The resulting HNFs were characterized by scanning electron microscopy, energy
      dispersive spectrometry, X-ray diffraction, and X-ray photoelectron spectroscopy.
      The HNFs possess a large specific surface area, and the CeO2 nanocrystals consist
      of a single phase. The HNFs display intrinsic peroxidase-like activity and can
      catalyze the oxidation of the peroxidase substrate 3,3',5,5'-tetramethylbenzidine
      in the presence of H2O2 to produce a blue product. The method was applied to the
      quantification of H2O2 with a 5.2 nM detection limit. The analytical range is
      from 10 nM to 1 MUM. Graphical abstract Schematic of the preparation of a 3
      dimensional C/CeO2 hollow nanostructure framework by a polyvinylpyrrolidone
      blowing process accelerated by Ce(NO3)3. They were applied to H2O2 detection by
      catalyzing the oxidation of peroxidase substrate 3,3',5,5'-tetramethylbenzidine
      (TMB) to the oxidized 3,3',5,5'-tetramethylbenzidine (oxTMB) to produce blue
      color reaction.

PMID- 30120585
TI  - Characterization of an artificial skull cap for cranio-maxillofacial surgery
      training.
AB  - Cranial grafts are favored to reconstruct skeletal defects because of their
      reduced resorption and their histocompatibility. Training possibilities for
      novice surgeons include the "learning by doing" on the patient, specimens or
      simulators. Although the acceptance of simulators is growing, the major drawback
      is the lack of validated bone models. The aim of this study was to create and
      validate a realistic skull cap model and to show superiority compared to a
      commercially available skull model. Characteristic forces during machinery
      procedures were recorded and thickness parameters from the bony layers were
      obtained. The thickness values of the bone layers of the developed parietal bone
      were comparable to the human ones. Differences between drilling and sawing forces
      of human and artificial bones were not detected using statistical analysis. In
      contrast the parameters of the commercially available skull model were
      significantly different. However, as a result, a model-based simulator for tabula
      externa graft lift training, consisting of a brain, skull bone cap and covering
      soft tissues was created. This simulator enables the training of all procedural
      steps of a "split thickness graft lift". In conclusion, an artificial skull cap
      suitable for parietal graft lift training was manufactured and validated against
      human parietal bones.

PMID- 30120587
TI  - Enhanced cellular osteogenic differentiation on Zn-containing bioglass
      incorporated TiO2 nanorod films.
AB  - Surface nanotopography and bioactive ions have been considered to play critical
      roles on the interactions of biomaterials with cells. In this study, a TiO2
      nanorod film incorporated with Zn-containing bioactive glass (TiO2/Zn-BG) was
      prepared on tantalum substrate, trying to evaluate the synergistic effects of
      nanotopograpgy and bioactive ions to promote cellular osteogenic differentiation
      activity. The expression of osteogenic-related genes, ALP as well as the ECM
      mineralization on TiO2/Zn-BG film were significantly upregulated compared to that
      of the film without TiO2 nanorod nanostructure (Zn-BG) or without Zn (TiO2/BG).
      Moreover, a much low Zn2+ release level on TiO2/Zn-BG film was beneficial to
      promote the osteogenesis, which could be ascribed to that a semi-closed space
      established by TiO2 nanorods with adhered cells provided an appropriate micro
      environment that facilitated Zn2+ adsorption.

PMID- 30120588
TI  - The effects of raw propolis on Varroa-infested honey bee (Apis mellifera)
      workers.
AB  - Self-medication plays a major role in the behavioral defense against pathogens
      and parasites that animals have developed during evolution. The conditions
      defining this adaptive behavior are: (1) contact with the substance in question
      must be deliberate; (2) the substance must be detrimental to one or more
      parasites; (3) the detrimental effect on parasites must lead to increased host
      fitness. Recent studies have shown that A. mellifera colonies are able to
      increase resin foraging rates when infested by V. destructor, whereas further
      investigations are needed for evidence of parasite and host fitness. In order to
      understand whether Varroa-infested colonies could benefit from increasing levels
      of resin, we carried out laboratory bioassays to investigate the effects of
      propolis on the fitness of infested workers. The longevity and energetic stress
      of adult bees kept in experimental cages and artificially infested with the mite
      were thus monitored over time. At the same time, in vitro experiments were
      performed to study the contact effects of crude propolis on Varroa mites. Our
      results clearly demonstrate the positive effects of raw propolis on the lifespan
      of Varroa-infested adult bees. A low narcoleptic effect (19-22%) of raw propolis
      on phoretic mites after 5 h was also observed. In terms of energetic stress, we
      found no differences between Varroa-free and Varroa-infested bees in terms of the
      daily sucrose solution demand. Our findings seem to confirm the hypothesis that
      resin collection and propolis use in the hive represent an example of self
      medication behavior in social insects.

PMID- 30120589
TI  - MaxEnt modeling of soil-transmitted helminth infection distributions in Thailand.
AB  - Infections due to soil-transmitted helminths (STHs), i.e. Ascaris lumbricoides,
      Trichuris trichiura, hookworms, and Strongyloides stercoralis, are widely
      distributed in tropical and subtropical areas in which approximately 1.5 billion
      people are infected. A clear understanding of the epidemiology and distribution
      of diseases is an important aid for control and prevention. The aim of our study
      was to identify the effects of environmental and climatic factors on distribution
      patterns of STHs and to develop a risk map for STH infections under current
      environmental and climate regimes in Thailand. Geographical information systems
      (GIS), remote sensing, and Maximum Entropy (MaxEnt) algorithm software were used
      to determine the significant factors and to create predictive risk maps for STH
      infections in Thailand. The disease data from Thailand covered the years from
      1969 to 2014, while environmental and climatic data were compiled from the
      Worldclim database, MODIS satellite imagery, Soilgrids and ISCGM. The models
      predicted that STHs occur mainly in southern Thailand. Mean annual precipitation
      was the factor most affecting the current distribution of A. lumbricoides, T.
      trichiura, and S. stercoralis. Land cover class was the main predictor for
      distribution of S. stercoralis and important for hookworms. Altitude was the
      dominant factor affecting the distribution of hookworms, and mean temperature of
      the wettest quarter was significantly associated with A. lumbricoides
      distribution. A predicted distribution map of STHs to identify environmental risk
      factors in Thailand is presented. This work provides a model for use in STH
      monitoring and health planning not only in Thailand but also in other countries
      with similar disease conditions.

PMID- 30120591
TI  - Study of the antimalarial activity of 4-aminoquinoline compounds against
      chloroquine-sensitive and chloroquine-resistant parasite strains.
AB  - This study is concerned with identifying features of 4-aminoquinoline scaffolds
      that can help pinpoint characteristics that enhance activity against chloroquine
      resistant parasites. Statistically valid predictive models are reported for a
      series of 4-aminoquinoline analogues that are active against chloroquine
      sensitive (NF54) and chloroquine-resistant (K1) strains of Plasmodium falciparum.
      Quantitative structure activity relationship techniques, based on statistical and
      machine learning methods such as multiple linear regression and partial least
      squares, were used with a novel pruning method for the selection of descriptors
      to develop robust models for both strains. Inspection of the dominant descriptors
      supports the hypothesis that chemical features that enable accumulation in the
      food vacuole of the parasite are key determinants of activity against both
      strains. The hydrophilic properties of the compounds were found to be crucial in
      predicting activity against the chloroquine-sensitive NF54 parasite strain, but
      not in the case of the chloroquine-resistant K1 strain, in line with previous
      studies. Additionally, the models suggest that 'softer' compounds tend to have
      improved activity for both strains than do 'harder' ones. The internally and
      externally validated models reported here should also prove useful in the future
      screening of potential antimalarial compounds for targeting chloroquine-resistant
      strains. Graphical Abstract Predictive models reveal linear relationships for
      activity of 4-aminoquinoline analogues active against chloroquine-sensitive
      strains of Plasmodium falciparum.

PMID- 30120590
TI  - Histopathological, morphological, and molecular characterization of Sarcocystis
      species in elk (Cervus elaphus) from Pennsylvania, USA.
AB  - Sarcocystis sarcocysts are common in many species of domestic and wild animals.
      Here, we report sarcocystosis in muscles from 91 free range elk (Cervus elaphus)
      from Pennsylvania, USA, tested by histopathology, transmission electron
      microscopy (TEM), and DNA sequencing. Sarcocysts were detected in hematoxylin and
      eosin (HE)-stained sections from 83 of 91 (91.2%) elk, including 83/91 (91.2%)
      tongues and 15/17 (88.2%) hearts. With respect to age, sarcocysts were found in
      0/5 calves, 8/9 (88.8%) yearlings, and 75/77 (97.4%) adults. Sarcocysts were
      identified in 62/69 (89.4%) females and 21/22 (91.2%) males. Associated lesions
      were mild and consisted of inflammatory foci around degenerate sarcocysts. There
      were two morphologically distinct sarcocysts based on wall thickness, thin (< 0.5
      MUm) and thick-walled (> 4.0 MUm). Thin-walled sarcocysts had a TEM "type 2" and
      villar protrusions (vps), identical to Sarcocystis wapiti previously described
      from elk in western USA. This species was present both in tongue and heart
      samples and was detected in all infected elk. Thick-walled sarcocysts consisted
      of three morphologic variants, referred to herein as subkinds A, B, C. Subkind A
      sarcocysts were rare; only four sarcocysts were found in three elk.
      Histologically, they had a 5-8-MUm thick wall with tufted vp. By TEM, the
      sarcocyst wall was "type 12" and appeared similar to Sarcocystis sybillensis,
      previously described from elk in USA. Subkind B, Sarcocystis sp.1 sarcocysts were
      also rare, found in only 1 elk. These sarcocysts had 6.7-7.3-MUm-thick wall with
      TEM "type 15b" vp. Subkind C Sarcocystis sp.2 sarcocysts were more common
      (22/91). Morphologically, the sarcocyst wall was 6.1-6.8 MUm thick and contained
      "type 10b" vp. Comparisons of ribosomal DNA loci with published sequences
      indicated all sarcocysts were similar to what has previously been isolated from
      cervid hosts across the northern hemisphere. Phylogenetic analysis placed the
      thin-walled S. wapiti within a strongly supported clade with S. linearis and S.
      taeniata, while the thick-walled cysts were very closely related to S. truncata,
      S. elongata, S. silva, and S. tarandi. Further sequencing is needed to produce
      molecular diagnostics to distinguish among these species. North American elk are
      hosts to multiple Sarcocystis species with diverse morphology, deriving from two
      separate evolutionary lineages.

PMID- 30120593
TI  - Abstracts : 30th European Congress of Pathology.

PMID- 30120592
TI  - Immunotherapy in Prostate Cancer: Teaching an Old Dog New Tricks.
AB  - Immunotherapy is rapidly transforming cancer care across a range of tumor types.
      Although Sipuleucel-T represented the first successful vaccine for the treatment
      of established cancer, other immunotherapeutic approaches for prostate cancer
      such as checkpoint inhibitors have been relatively disappointing to date.
      However, significant promise is on the horizon as there is a wide array trials
      evaluating immunotherapy in prostate cancer patients. These include both immune
      checkpoint inhibitors and antigen-specific approaches including vaccines,
      antibody-drug conjugates, and antitumor antibodies. Furthermore, a better
      understanding of the key mechanisms that promote the immunosuppressive
      microenvironment of prostate cancer is emerging. These insights may eventually
      make it possible to determine which patients will benefit from immunotherapy.
      This review will discuss the successes and failures of immunotherapy in prostate
      cancer. We will also present key lessons learned from completed trials and
      highlight important ongoing studies.

PMID- 30120594
TI  - Association of HER2 gene amplification and tumor progression in early gastric
      cancer.
AB  - Overexpression of human epidermal growth factor receptor 2 (HER2) protein in
      association with HER2 gene amplification is found in 7-34% of gastric cancers. In
      breast cancer, HER2 overexpression is a prognostic factor in advanced cases and
      is associated with tumor progression in ductal carcinoma in situ. However, the
      biological and clinical significance of HER2 status in early gastric cancer is
      unknown. Here, we aimed to examine the correlation between HER2 gene
      amplification and tumor progression in early gastric cancer. The HER2 status was
      evaluated in 149 lesions from 141 consecutive patients with early gastric cancer
      who underwent endoscopic resection by immunohistochemistry and dual color in situ
      hybridization. HER2 gene amplification was detected in 35 (23.5%) of 149 lesions,
      and of those, 26 cases (74.3%) showed intratumoral heterogeneity. HER2 gene
      amplification was found in noninvasive carcinoma, and there was a significant
      correlation between HER2 status and T factor (P = 0.0290). Our study demonstrated
      that HER2 gene amplification occurred during the early stages of gastric cancer
      and showed heterogeneity in several cases. HER2 gene amplification may be
      involved in tumor progression in early gastric cancer.

PMID- 30120596
TI  - Clogging-free continuous operation with whole blood in a radial pillar device
      (RAPID).
AB  - Pillar-based passive microfluidic devices combine the advantages of simple
      designs, small device footprint, and high selectivity for size-based separation
      of blood cells. Most of these device designs have been validated with dilute
      blood samples. Handling whole blood in pillar-based devices is extremely
      challenging due to clogging. The high proportion of cells (particularly red blood
      cells) in blood, the varying sizes and stiffness of the different blood cells,
      and the tendency of the cells to aggregate lead to clogging of the pillars within
      a short period. We recently reported a ra dial pi llar d evice (RAPID) design for
      continuous and high throughput separation of multi-sized rigid polystyrene
      particles in a single experiment. In the current manuscript, we have given
      detailed guidelines to modify the design of RAPID for any application with
      deformable objects (e.g. cells). We have adapted RAPID to work with whole blood
      without any pre-processing steps. We were successful in operating the device with
      whole blood for almost 6 h, which is difficult to achieve with most pillar-based
      devices. The availability of multiple parallel paths for the cells and the
      provision for a self-generating cross flow in the device design were the main
      reasons behind the minimal clogging in our device. We also observed that a
      vibrator motor attached to the inlet tubing occasionally disturbed the cell
      clumps. As an illustration of the improved device design, we demonstrated up to ~
      60-fold enrichment of platelets.

PMID- 30120597
TI  - Resistance and Raman spectroscopy analysis of Parageobacillus thermantarcticus
      spores after gamma-ray exposure.
AB  - Spores of the genus Bacillus are able to resist ionizing radiations and therefore
      they are a suitable biological model for studies in Astrobiology, i.e. the
      multidisciplinary approach to the study of the origin and evolution of life on
      Earth and in the universe. The resistance to gamma-radiation is an important
      issue in Astrobiology in relation to the search for bacterial species that could
      adapt to life in space. This study investigates the resistance of spores of the
      thermophilic bacteria Parageobacillus thermantarcticus to gamma-rays. The
      analysis of spores' response to irradiation at a molecular level is performed by
      means of Raman spectroscopy that allows to get insights in the sequence of events
      taking place during inactivation. The role of the gamma-rays' dose in the
      inactivation of spores is also investigated, allowing to highlight the
      mechanism(s) of inactivation including DNA damage, protein denaturation and
      calcium dipicolinate levels.

PMID- 30120599
TI  - Bacterial and archaeal profiling of hypersaline microbial mats and
      endoevaporites, under natural conditions and methanogenic microcosm experiments.
AB  - Bacterial and archaeal community structure of five microbial communities,
      developing at different salinities in Baja California Sur, Mexico, were
      characterized by 16S rRNA sequencing. The response of the microbial community to
      artificial changes in salinity-sulfate concentrations and to addition of
      trimethylamine was also evaluated in microcosm experiments. Ordination analyses
      of the microbial community structure showed that microbial composition was
      distinctive for each hypersaline site. Members of bacteria were dominated by
      Bacteroidetes and Proteobacteria phyla, while Halobacteria of the Euryarchaeota
      phylum was the most represented class of archaea for all the environmental
      samples. At a higher phylogenetic resolution, methanogenic communities were
      dominated by members of the Methanosarcinales, Methanobacteriales and
      Methanococcales orders. Incubation experiments showed that putative
      hydrogenotrophic methanogens of the Methanomicrobiales increased in abundance
      only under lowest salinity and sulfate concentrations. Trimethylamine addition
      effectively increased the abundance of methylotrophic members from the
      Methanosarcinales, but also increased the relative abundance of the
      Thermoplasmata class, suggesting the potential capability of these microorganisms
      to use trimethylamine in hypersaline environments. These results contribute to
      the knowledge of microbial diversity in hypersaline environments from Baja
      California Sur, Mexico, and expand upon the available information for uncultured
      methanogenic archaea in these ecosystems.

PMID- 30120600
TI  - Pre-treatment with sumatriptan for cilostazol induced headache in healthy
      volunteers.
AB  - BACKGROUND: Previous studies indicate that sumatriptan is not effective when
      second messenger levels are high as after cilostazol provocation. Therefore, we
      have conducted the present study, where sumatriptan is administrated as
      pretreatment before cAMP increases due to cilostazol intake. Our hypothesis was
      that pretreatment with sumatriptan would have a significant effect against
      cilostazol induced headache in healthy volunteers. METHODS: In a double-blind,
      randomized, crossover design, 30 healthy volunteers of both sexes received
      cilostazol 200 mg on two separate days, each day preceded by oral sumatriptan (2
      * 50 mg) or placebo. Headache response and accompanying symptoms were registered
      in a questionnaire by the participants themselves. RESULTS: Cilostazol induced a
      mild to moderate headache in all but 3 participants (Range 0-7 on Numerical
      Rating Scale). There was no significant difference in headache score 2 h (p =
      0.67) or 4 h (p = 0.1) after treatment between the 2 days. Median peak headache
      score was 1.5 (range 0-5) on the sumatriptan day and 2 (range 0-7) on the placebo
      day (p = 0.26). CONCLUSION: Pre-treatment with sumatriptan prevents cilostazol
      induced headache from developing. However, the placebo group did not develop
      enough headache to get statistical significant results. The cilostazol pre
      treatment model is valuable for experimental headache research and perhaps for
      testing drugs with another mechanism of action. TRIAL REGISTRATION:
      ClinicalTrials.gov Identifier: NCT03156920 .

PMID- 30120598
TI  - Characterization of protistan plankton diversity in ancient salt evaporation
      ponds located in a volcanic crater on the island Sal, Cape Verde.
AB  - Salinity is an important factor when exploring the limits known for life.
      Therefore, hypersaline systems have attracted much attention in recent years. In
      this study, we investigated the protistan diversity and community composition in
      two natural salt evaporation ponds (27-30% salinity) located in an ancient
      volcanic crater on the Cape Verde island Sal using high-throughput DNA
      sequencing. Our study revealed a broad range of protistan taxa and a high
      taxonomic diversity within the Ciliophora, Dinophyceae, and Chlorophyta. We
      detected a total of 23 Dinophyceae families, although Dinophyceae were generally
      considered to be only this diverse in aquatic environments of less than 10%
      salinity. Moreover, we uncovered a high degree of genetic novelty in this
      habitat. The mean similarity of all detected OTUs to previously described
      sequences was only 93.6%. These findings strongly dispute the traditional view
      that extreme hypersaline environments generally maintain low protistan diversity.
      A meta-analysis covering our and previously published data from other inland and
      coastal salt ponds clearly showed that our samples clustered according to
      salinity and not biogeography. This result further supports the claim that
      salinity is a major transition boundary for protistan communities, regardless of
      their biogeographic origin.

PMID- 30120602
TI  - Genome-wide analysis of oligopeptide transporters and detailed characterization
      of yellow stripe transporter genes in hexaploid wheat.
AB  - Oligopeptide transporters (OPT) are integral cell membrane proteins that play a
      critical role in the transport of small peptides, secondary amino acids,
      glutathione conjugates, and mineral uptake. In the present study, 67 putative
      wheat yellow stripe-like transporter (YSL) proteins belonging to the subfamily of
      OPT transporters were identified. Phylogeny analysis resulted in the distribution
      of wheat YSLs into four discrete clades. The highest number of YSLs was present
      on the A genome and the chromosome 2 of hexaploid wheat. The identified wheat YSL
      genes showed differential expression in different tissues and during grain
      development suggesting the importance of this subfamily. Gene expression pattern
      of TaYSLs during iron starvation experiments suggested an early high transcript
      accumulation of TaYS1A, TaYS1B, TaYSL3, TaYSL5, and TaYSL6 in roots. In contrast,
      delayed expression was observed in shoots for TaYS1A, TaYS1B, TaYSL5, TaYSL12,
      and TaYSL19 as compared to control. Further, their expression under biotic and
      abiotic response emphasized their alternative functions during the plant growth
      and development. In conclusion, this work is the first comprehensive study of
      wheat YSL transporters and would be an important resource for prioritizing genes
      towards wheat biofortification.

PMID- 30120603
TI  - Involvement of HPI-axis in anesthesia with Lippia alba essential oil citral and
      linalool chemotypes: gene expression in the secondary responses in silver
      catfish.
AB  - In teleost fish, stress initiates a hormone cascade along the hypothalamus
      pituitary-interrenal (HPI) axis to provoke several physiological reactions in
      order to maintain homeostasis. In aquaculture, a number of factors induce stress
      in fish, such as handling and transport, and in order to reduce the consequences
      of this, the use of anesthetics has been an interesting alternative. Essential
      oil (EO) of Lippia alba is considered to be a good anesthetic; however, its
      distinct chemotypes have different side effects. Therefore, the present study
      aimed to investigate, in detail, the expression of genes involved with the HPI
      axis and the effects of anesthesia with the EOs of two chemotypes of L. alba
      (citral EO-C and linalool EO-L) on this expression in silver catfish, Rhamdia
      quelen. Anesthesia with the EO-C is stressful for silver catfish because there
      was an upregulation of the genes directly related to stress: slc6a2, crh, hsd20b,
      hspa12a, and hsp90. In this study, it was also possible to observe the importance
      of the hsd11b2 gene in the response to stress by handling. The use of EO-C as
      anesthetics for fish is not recommended, but, the use of OE-L is indicated for
      silver catfish as it does not cause major changes in the HPI axis.

PMID- 30120604
TI  - Effect of fiber incorporation on the contraction stress of composite materials.
AB  - OBJECTIVES: This study aimed to assess the effects of fiber incorporation on the
      contraction stress (CS), time to gelation (TG), and temperature rise (TR)
      features of two experimental resin-based composites (RBCs) in comparison to those
      of bulk-fill RBCs and conventional RBCs in simulated, clinically relevant
      cavities. MATERIALS AND METHODS: CS over 300 s, TG and TR were assessed by a
      stress-strain analyzer (SSA T80) in two cavity configurations (2 * 4 * 4 mm3/4 *
      4 * 4 mm3/configuration value [Formula: see text] and [Formula: see text]) for
      two experimental RBCs, eight bulk-fill RBCs (EverX Posterior, Filtek Bulk Fill,
      SDR, SonicFill, Tetric EvoCeram Bulk Fill, Venus Bulk Fill, X-tra base, and X-tra
      Fill) and one RBC (Filtek Supreme XTE) by light curing (1200 mW/cm2) (n = 10).
      The experimental materials used were based on EverX Posterior with modifications
      made to the fiber and filler content. Statistical analyses were performed via
      ANOVA; multiple pair-wise comparisons were performed via Tukey's test, and
      homogeneous subsets were identified ("multcomp" package, R). RESULTS: CS values
      ranged from 1.00 to 4.07 MPa (2 * 4 * 4 mm3) and from 0.97 to 2.49 MPa (4 * 4 * 4
      mm3); TG values ranged from 1.31 to 4.05 s (2 * 4 * 4 mm3) and from 1.39 to 3.84
      s (4 * 4 * 4 mm3). SDR values showed lowest stress values in both cavity
      configurations. The experimental composite with fibers presented significantly
      higher stress values than did the experimental composite without fibers.
      CONCLUSION: Bulk-fill RBCs showed lower levels of stress than did conventional
      RBCs. The incorporation of fibers had no positive impact on the CS and TG.
      CLINICAL RELEVANCE: Appropriate material selection may be essential to clinical
      success because certain RBCs exhibit higher CS, TG, and TR values.

PMID- 30120601
TI  - Predictive classification models and targets identification for betulin
      derivatives as Leishmania donovani inhibitors.
AB  - Betulin derivatives have been proven effective in vitro against Leishmania
      donovani amastigotes, which cause visceral leishmaniasis. Identifying the
      molecular targets and molecular mechanisms underlying their action is a currently
      an unmet challenge. In the present study, we tackle this problem using
      computational methods to establish properties essential for activity as well as
      to screen betulin derivatives against potential targets. Recursive partitioning
      classification methods were explored to develop predictive models for 58 diverse
      betulin derivatives inhibitors of L. donovani amastigotes. The established models
      were validated on a testing set, showing excellent performance. Molecular
      fingerprints FCFP_6 and ALogP were extracted as the physicochemical properties
      most extensively involved in separating inhibitors from non-inhibitors. The
      potential targets of betulin derivatives inhibitors were predicted by in silico
      target fishing using structure-based pharmacophore searching and compound
      pharmacophore-target-pathway network analysis, first on PDB and then among L.
      donovani homologs using a PSI-BLAST search. The essential identified proteins are
      all related to protein kinase family. Previous research already suggested members
      of the cyclin-dependent kinase family and MAP kinases as Leishmania potential
      drug targets. The PSI-BLAST search suggests two L. donovani proteins to be
      especially attractive as putative betulin target, heat shock protein 83 and
      membrane transporter D1.

PMID- 30120605
TI  - Three-year clinical evaluation of high-viscosity glass ionomer restorations in
      non-carious cervical lesions: a randomised controlled split-mouth clinical trial.
AB  - OBJECTIVE: To compare the 3-year clinical performance of high-viscosity glass
      ionomer restorations with that of composite restorations in non-carious cervical
      lesions (NCCLs). MATERIALS AND METHODS: One hundred thirty-four NCCLs were
      randomised into two groups according to a split-mouth design. In the experimental
      group (Hv-GIC), lesions were restored with a high-viscosity glass ionomer (EQUIA
      Fil, GC), whereas a composite resin (G-aenial, GC) was applied in the control
      group (E&Ra/comp). All restorative materials were used according to the
      manufacturers' instructions. Clinical evaluations were performed after 1 week, 6
      months, 1 year, 2 years, and 3 years using FDI (World Dental Federation)
      criteria. Data were analysed using Friedman's ANOVA and Mann-Whitney U tests
      (alpha = 0.05). RESULTS: While retention rates of the Hv-GIC group were 98.5%,
      96%, 91%, and 87% in respective evaluation periods, no retention loss was
      observed in the E&Ra/comp group at any time. There was a statistically
      significant difference between study groups regarding the retention criterion in
      both the second and third years (p = 0.008 and p = 0.003, respectively).
      Furthermore, there was a statistically significant difference between the groups
      in terms of surface lustre at the third-year recall, in favour of the E&Ra/comp
      group (p = 0.022). CONCLUSIONS: The 3-year clinical performance of E&Ra/comp
      restorations in NCCLs was better than that of Hv-GIC restorations. The most
      common problems in Hv-GIC restorations were a loss of retention and reduction in
      surface lustre. CLINICAL RELEVANCE: Although the 3-year clinical performance of
      Hv-GIC restorations in non-retentive lesions was acceptable, it was worse than in
      composites. The operator should consider the benefit/loss ratio of Hv-GIC when
      he/she decides to use this material in non-retentive cavities, especially those
      that are shallow.

PMID- 30120606
TI  - Candidate gene sequencing reveals mutations causing hypoplastic amelogenesis
      imperfecta.
AB  - OBJECTIVE: Amelogenesis imperfecta (AI) is a rare hereditary disorder affecting
      the quality and quantity of the tooth enamel. The purpose of this study was to
      identify the genetic etiology of hypoplastic AI families based on the candidate
      gene approach. MATERIALS AND METHODS: We recruited three Turkish families with
      hypoplastic AI and performed a candidate gene screening based on the
      characteristic clinical feature to find the pathogenic genetic etiology. RESULTS:
      The candidate gene sequencing of the LAMB3 gene for family 1 revealed a
      heterozygous nonsense mutation in the last exon [c.3431C > A, p.(Ser1144*)].
      FAM20A gene sequencing for families 2 and 3 identified a homozygous deletion
      [c.34_35delCT, p.(Leu12Alafs*67)] and a homozygous deletion-insertion (c.1109 +
      3_1109 + 7delinsTGGTC) mutation, respectively. CONCLUSION: The candidate gene
      approach can be successfully used to identify the genetic etiology of the AI in
      some cases with characteristic clinical features. CLINICAL RELEVANCE:
      Identification of the genetic etiology of the AI will help both the family
      members and dentist understand the nature of the disorder. Characteristic
      clinical feature can suggest possible genetic causes.

PMID- 30120607
TI  - Quasilocalized states of self stress in packing-derived networks.
AB  - States of self stress (SSS) are assignments of forces on the edges of a network
      that satisfy mechanical equilibrium in the absence of external forces. In this
      work we show that a particular class of quasilocalized SSS in packing-derived
      networks, first introduced by D.M. Sussman, C.P. Goodrich, A.J. Liu (Soft Matter
      12, 3982 (2016)), are characterized by a decay length that diverges as [Formula:
      see text] , where [Formula: see text] is the mean connectivity of the network,
      and [Formula: see text] is the Maxwell threshold in two dimensions, at odds with
      previous claims. Our results verify the previously proposed analogy between
      quasilocalized SSS and the mechanical response to a local dipolar force in random
      networks of relaxed Hookean springs. We show that the normalization factor that
      distinguishes between quasilocalized SSS and the response to a local dipole
      constitutes a measure of the mechanical coupling of the forced spring to the
      elastic network in which it is embedded. We further demonstrate that the
      lengthscale that characterizes quasilocalized SSS does not depend on its
      associated degree of mechanical coupling, but instead only on the network
      connectivity.

PMID- 30120608
TI  - FESAEI: a fuzzy rule-based expert system for the assessment of environmental
      impacts : A fuzzy logic approach to impact assessment.
AB  - Currently, the method mostly used by practitioners of environmental impact
      assessment (EIA) is the "crisp numbers" method. Nevertheless, this arithmetic
      method is far away of giving correct values due to its rigidity and the lack of
      consideration of important aspects as the imprecision and incompleteness of data
      and the uncertainty that usually pervade our knowledge of environment. A more
      flexible model that considers uncertainty of knowledge and imprecision of data is
      necessary. Among the different approaches for the assessment of environmental
      impacts, the fuzzy logic-based one takes account of the aspects said before; this
      was our primal assumption. On this paper, we explain the structure and
      performance of the fuzzy rule-based inference model we built, how it works, and
      what can be obtained when used to assess environmental impacts. Our fuzzy expert
      system for the assessment of environmental impacts (FESAEI) is built as the
      combination of five subsystems, using a total of 120 fuzzy rules, and being the
      output and input for the next subsystem. We assessed the parameters of rarity,
      robustness, quality, recoverability, intrinsic value, extension, intensity,
      persistence, impact_character, cumulativeness, transmissivity, and impact
      prevalue in four subsystems. The fifth subsystem gives the definitive impact
      value corresponding to the impact type of "compatible," "moderate," "severe," and
      "critical." The model is verified and statistically validated. Weighted Cohen's
      kappa shows an almost perfect concordance among experts and FESAEI's evaluations.

PMID- 30120610
TI  - On-ward surgical management of wound dehiscence: report of a single neurosurgical
      center experience and comparison of safety and effectiveness with conventional
      treatment.
AB  - The early identification and optimized treatment of wound dehiscence are a
      complex issue, with implications on the patient's clinical and psychological
      postoperative recovery and on healthcare system costs. The most widely accepted
      treatment is surgical debridement (also called "wash out"), performed in theater
      under general anesthesia (GA), followed by either wide-spectrum or targeted
      antibiotic therapy. Although usually effective, in some cases, such a strategy
      may be insufficient (generally ill, aged, or immunocompromised patients; poor
      tissue conditions). Moreover, open revision may still fail, requiring further
      surgery and, therefore, increasing patients' discomfort. Our objective was to
      compare the effectiveness, costs, and patients' satisfaction of conventional
      surgical revision with those of bedside wound dehiscence repair. In 8 years'
      time, we performed wound debridement in 130 patients. Two groups of patients were
      identified. Group A (66 subjects) underwent conventional revision under GA in
      theater; group B (64 cases) was treated under local anesthesia in a protected
      environment on the ward given their absolute refusal to receive further surgery
      under GA. Several variables-including length and costs of hospital stay,
      antibiotic treatment modalities, and success and resurgery rates-were compared.
      Permanent wound healing was observed within 2 weeks in 59 and 55 patients in
      groups A and B, respectively. Significantly reduced costs, shorter antibiotic
      courses, and similar success rates and satisfaction levels were observed in group
      B compared with group A. In our experience, the bedside treatment of wound
      dehiscence proved to be safe, effective, and well-tolerated.

PMID- 30120611
TI  - The effect of tumor removal via craniotomies on preoperative hydrocephalus in
      adult patients with intracranial tumors.
AB  - The efficacy of tumor removal via craniotomies on preoperative hydrocephalus (HC)
      in adult patients with intracranial tumors is largely unknown. Therefore, we
      sought to evaluate the effect of tumor resection in patients with preoperative HC
      and identify the incidence and risk factors for postoperative VP shunt
      dependency. All craniotomies for intracranial tumors at Oslo University Hospital
      in patients >= 18 years old during a 10-year period (2004-2013) were reviewed.
      Patients with radiologically confirmed HC requiring surgery and subsequent
      development of shunt dependency were identified by cross-linking our
      prospectively collected tumor database to surgical procedure codes for
      hydrocephalus treatment (AAF). Patients with preexisting ventriculoperitoneal
      (VP) shunts (N = 41) were excluded. From 4774 craniotomies performed on 4204
      patients, a total of 373 patients (7.8%) with HC preoperatively were identified.
      Median age was 54.4 years (range 18.1-83.9 years). None were lost to follow-up.
      Of these, 10.5% (39/373) required permanent CSF shunting due to persisting
      postoperative HC. The risk of becoming VP shunt dependent in patients with
      preexisting HC was 7.0% (26/373) within 30 days and 8.9% (33/373) within 90 days.
      Only secondary (repeat) surgery was a significant risk factor for VP shunt
      dependency. In this large, contemporary, single-institution consecutive series,
      10.5% of intracranial tumor patients with preoperative HC became shunt-dependent
      post-craniotomy, yielding a surgical cure rate for HC of 89.5%. To the best of
      our knowledge, this is the first and largest study regarding postoperative shunt
      dependency after craniotomies for intracranial tumors, and can serve as benchmark
      for future studies.

PMID- 30120612
TI  - Theoretical Assumptions on Pornography Problems Due to Moral Incongruence and
      Mechanisms of Addictive or Compulsive Use of Pornography: Are the Two
      "Conditions" as Theoretically Distinct as Suggested?

PMID- 30120609
TI  - NLRP1 promotes TGF-beta1-induced myofibroblast differentiation in neonatal rat
      cardiac fibroblasts.
AB  - Nuclear localization leucine-rich-repeat protein 1 (NLRP1) is a member of Nod
      like receptors (NLRs) family. Recent studies have reported that NLRP1 is involved
      in various diseases, especially in cardiovascular diseases. However, the effect
      of NLRP1 on cardiac fibrosis remains unclear. In this study, NLRP1 overexpression
      and NLRP1 silencing constructs were transfected into neonatal rat cardiac
      fibroblasts induced by TGF-beta1 for 48 h to investigate the effect of NLRP1 in
      cardiac fibrosis and its molecular mechanisms. Cardiac fibroblasts were
      transfected with NLRP1 and then cultured in the presence and absence of TGF
      beta1and Smad3 inhibitor (SIS3). Our data indicated that NLRP1 not only promoted
      fibroblast activation and myofibroblast differentiation, but also upregulated the
      mRNA and protein levels of alpha-SMA in the TGF-beta1-treated neonatal rat
      cardiac fibroblasts. Overexpressing NLRP1 in TGF-beta1-induced cardiac
      fibroblasts upregulated the mRNA and protein levels of Collagen I, Collagen III,
      and connective tissue growth factor. Moreover, NLRP1 upregulated the protein
      levels of Smad2, Smad3, and Smad4 in nuclei of fibroblasts, and attenuated levels
      of phosphorylated Smad2 and Smad3 in the cytoplasm of fibroblasts induced by TGF
      beta1. In addition, the increase in fibrotic genes and Smad proteins was
      significantly reduced in the presence of SIS3. Our findings illustrated that
      NLRP1 promoted myofibroblast differentiation and excessive ECM production in TGF
      beta1-induced neonatal cardiac fibroblasts through directly targeting TGF
      beta1/Smad signaling pathways.

PMID- 30120613
TI  - Chemical characterization and ligand behaviour of Pseudomonas veronii 2E
      siderophores.
AB  - Siderophores are low-molecular weight ligands secreted by bacteria as a survival
      strategy in Fe(III)-lacking environments. They bind not only Fe(III), but Co(II),
      Zn(II), Mn(II), Ni(II), Ga(III) as a detoxification alternative. The synthesis,
      purification and characterization of siderophores produced by Pseudomonas veronii
      2E were evaluated to be applied in future environmental technologies. Optimal
      production was obtained in Fe(III)-free M9-succinate at 25  degrees C, 40 h and
      pH 6.9. Siderophores were chemically characterized as hydroxamate and catechol
      mixed-type. Spectroscopic analysis indicated their belonging to the pyoverdine
      family, behaving as ligand to Cd(II), Zn(II), Cu(II), Ni(II) and Cr(III), which
      promoted siderophoregenesis during growth. Siderophore-Cd(II) complexation was
      studied by electrochemical monitored titration revealing one family of moderate
      strength binding sites. Mass spectral analysis evidenced the secretion of a
      variety of molecules (molecular mass ca.1200 u). Non pathogenic Pseudomonas
      veronii 2E siderophores represent a safe alternative for the concrete application
      of environmental technologies and clinical procedures.

PMID- 30120614
TI  - Establishment and evaluation of a general dissociation technique for antibodies
      in circulating immune complexes.
AB  - This study aimed to establish a general and efficient dissociation technique for
      detecting antibodies in circulating immune complexes (CICs) in serum and to
      evaluate its clinical application. CICs were efficiently separated from specimens
      using polyethylene glycol double-precipitation. The best conditions for anti-HBs
      dissociation from HBsAg-ICs were a pH of 1.80, incubation at 15  degrees C for 5
      10 min, and detection within 10 min after neutralization. The mean dissociation
      rate, reproducibility, mean dissociation recovery rate and specificity of the new
      technique were 64.3%, < 5.97, 95.4 and 100%, respectively. They had a favourable
      linear relationship (r = 0.9932), and the stability of the reagents exceeded 24
      months, except the CIC antibody dissociation reagent (> 12 months). Conditions
      for the dissociation of other CICs tested were similar, but there were
      differences in the rate of antibody dissociation. Different HBV-M patterns had
      significantly different levels and rates of antibody dissociation from HBsAg-IC
      (P < 0.05), and the detection rates of the corresponding antibodies in HCV, core
      anti-HCV core antibody (HCV-ICs), HIV P24-anti-HIV P24 antibody (HIV-ICs),
      insulin-anti-insulin antibody (INS-ICs) and thyroid globulin-anti-thyroid
      globulin antibody CICs (TG-ICs) were 34.8, 66.7, 20 and 14.3%, respectively.
      These data suggest that our CIC antibody dissociation technique is a good general
      pretreatment technique for the detection of antibodies after the precipitation,
      separation and dissociation of multiple CICs.

PMID- 30120616
TI  - MRI quality assurance based on 3D FLAIR brain images.
AB  - OBJECTIVE: Quality assurance (QA) of magnetic resonance imaging (MRI) often
      relies on imaging phantoms with suitable structures and uniform regions. However,
      the connection between phantom measurements and actual clinical image quality is
      ambiguous. Thus, it is desirable to measure objective image quality directly from
      clinical images. MATERIALS AND METHODS: In this work, four measurements suitable
      for clinical image QA were presented: image resolution, contrast-to-noise ratio,
      quality index and bias index. The methods were applied to a large cohort of
      clinical 3D FLAIR volumes over a test period of 9.5 months. The results were
      compared with phantom QA. Additionally, the effect of patient movement on the
      presented measures was studied. RESULTS: A connection between the presented
      clinical QA methods and scanner performance was observed: the values reacted to
      MRI equipment breakdowns that occurred during the study period. No apparent
      correlation with phantom QA results was found. The patient movement was found to
      have a significant effect on the resolution and contrast-to-noise ratio values.
      DISCUSSION: QA based on clinical images provides a direct method for following
      MRI scanner performance. The methods could be used to detect problems, and
      potentially reduce scanner downtime. Furthermore, with the presented
      methodologies comparisons could be made between different sequences and imaging
      settings. In the future, an online QA system could recognize insufficient image
      quality and suggest an immediate re-scan.

PMID- 30120615
TI  - Metachronous skeletal muscle metastasis without any other organ metastases after
      curative gastrectomy: a case report.
AB  - BACKGROUND: Skeletal muscle metastasis from gastric cancer is extremely rare and
      often accompanied with synchronous metastasis to any other organs. We herein
      report a case of rapidly developing multiple skeletal metastases from gastric
      cancer without any other organ metastases. CASE PRESENTATION: A 47-year-old man
      underwent distal gastrectomy for advanced gastric cancer. Pathological diagnosis
      was poorly differentiated adenocarcinoma, T2N1M0, Stage IIA. The patient
      presented with a history of left dorsal tenderness 12 months after the operation.
      A computed tomography (CT) revealed a solid mass in the left latissimus dorsi
      muscle. Pathological examination of the ultrasound guided needle biopsy specimen
      revealed poorly differentiated adenocarcinoma similar to the previously resected
      gastric cancer, and the tumor was diagnosed as metastasis of gastric cancer.
      Thereafter, the systemic chemotherapy was administrated. However, the metastases
      were extended to the paraspinal muscle and quadriceps, and the patient died 7
      months after the recurrence. CONCLUSIONS: The prognosis of patients with skeletal
      muscle metastasis may be extremely poor, even in patients without any other organ
      metastases. The development of further chemotherapeutic agents and regimens is
      therefore needed.

PMID- 30120617
TI  - Preconditioning by Levosimendan is Mediated by Activation of Mitochondrial Ca2+
      Sensitive Potassium (mBKCa) Channels.
AB  - PURPOSE: Activation of mitochondrial large-conductance Ca2+-sensitive potassium
      (mBKCa)-channels is a crucial step for cardioprotection by preconditioning.
      Whether activation of these channels is involved in levosimendan-induced
      preconditioning is unknown. We investigated if cardioprotection by levosimendan
      requires activation of mBKCa-channels in the rat heart in vitro. METHODS: In a
      prospective blinded experimental laboratory investigation, hearts of male Wistar
      rats were randomized and placed on a Langendorff system, perfused with Krebs
      Henseleit buffer at a constant pressure of 80 mmHg. All hearts were subjected to
      33 min of global ischemia and 60 min of reperfusion. Before ischemia, hearts were
      perfused with different concentrations of levosimendan (0.03-1 MUM) for
      determination of a dose-effect curve. In a second set of experiments, 0.3 MUM
      levosimendan was administered in combination with the mBKCa-channel inhibitor
      paxilline (1 MUM). Infarct size was determined by TTC staining. RESULTS: In
      control, animal's infarct size was 58 +/- 7%. Levosimendan at a concentration of
      0.3 MUM reduced infarct size to 30 +/- 7% (P < 0.05 vs. control). Higher
      concentrations with 1 MUM levosimendan did not confer stronger protection.
      Paxilline completely blocked levosimendan-induced cardioprotection while
      paxilline alone had no effect on infarct size. CONCLUSIONS: This study shows that
      activation of mBKCa-channels plays a pivotal role in levosimendan-induced
      preconditioning.

PMID- 30120595
TI  - Practical guidelines for rigor and reproducibility in preclinical and clinical
      studies on cardioprotection.

PMID- 30120618
TI  - High and Intensive Care in Psychiatry: Validating the HIC Monitor as a Tool for
      Assessing the Quality of Psychiatric Intensive Care Units.
AB  - This study aims to validate the HIC monitor as a model-fidelity scale to the High
      and Intensive Care (HIC) model, a recently developed model for acute psychiatric
      wards. To assess the psychometric properties of the HIC monitor, 37 audits were
      held on closed inpatient wards at 20 psychiatric hospitals in the Netherlands.
      Interrater reliability, construct validity and content validity were examined.
      Our results suggest that the HIC monitor has good psychometric properties. It can
      be used as a tool for assessing the implementation of the HIC model on acute
      psychiatric wards in the Netherlands, and for quality assessment and improvement.

PMID- 30120619
TI  - An Overview of Safety Issues on Use of Insulin Pumps and Continuous Glucose
      Monitoring Systems in the Hospital.
AB  - PURPOSE OF REVIEW: Summarize safety issues related to patients using insulin pump
      therapy and continuous glucose monitoring systems (CGMS) in the outpatient
      setting when they are hospitalized and to review steps that can be taken to
      mitigate risk associated with use or discontinuation of these devices. RECENT
      FINDINGS: Two recent consensus conferences were held on the topics of inpatient
      use of insulin pumps and CGMS devices. In addition to commonly known safety
      issues (e.g., device malfunction, infection), cybersecurity and the vulnerability
      of contemporary technology to hacking have emerged. CGMS capabilities offer the
      promise of advancing the goal for development of glucometry (centralized
      monitoring of real-time glucose data). Strategies to assuring safe use of insulin
      pumps and CGMS in the hospital include collaboration between the patient and
      staff, proper patient selection, and clear policies and procedures outlining safe
      use. Available data indicates few adverse events associated with these devices in
      the hospital. Current data suggests, with proper patient selection and a clear
      process in place for glycemic management, that adverse events are rare, and
      consensus favors allowing use of the technology in the hospital. The topic of
      insulin pump and CGMS in the hospital would greatly benefit from more
      institutions reporting on their experiences and prospective clinical trials.

PMID- 30120620
TI  - Engineering Yarrowia lipolytica for the production of cyclopropanated fatty
      acids.
AB  - Traditional synthesis of biodiesel competes with food sources and has limitations
      with storage, particularly due to limited oxidative stability. Microbial
      synthesis of lipids provides a platform to produce renewable fuel with improved
      properties from various renewable carbon sources. Specifically, biodiesel
      properties can be improved through the introduction of a cyclopropane ring in
      place of a double bond. In this study, we demonstrate the production of C19
      cyclopropanated fatty acids in the oleaginous yeast Yarrowia lipolytica through
      the heterologous expression of the Escherichia coli cyclopropane fatty acid
      synthase. Ultimately, we establish a strain capable of 3.03 +/- 0.26 g/L C19
      cyclopropanated fatty acid production in bioreactor fermentation where this
      functionalized lipid comprises over 32% of the total lipid pool. This study
      provides a demonstration of the flexibility of lipid metabolism in Y. lipolytica
      to produce specialized fatty acids.

PMID- 30120622
TI  - An updated analysis with 45,078 subjects confirms the association between SNCA
      rs11931074 and Parkinson's disease.
AB  - Large-scale genome-wide association study (GWAS) has identified that the alpha
      synuclein (SNCA) rs11931074 polymorphism is associated with Parkinson's disease
      (PD) susceptibility in individuals of Japanese descent. Subsequently, a number of
      replication studies have been performed in Asian and Caucasian populations.
      However, the results remain controversial due to the relatively small sample
      sizes and genetic heterogeneity. Here, to overcome the limitations of individual
      studies, we reevaluated this association with data from 33 independent studies
      involving 15,368 patients and 29,710 control samples identified by searching
      PubMed and EMBase databases. Odds ratios (OR) with 95% confidence interval (CI)
      were applied to assess the association between SNCA rs11931074 polymorphism and
      PD. Heterogeneity, sensitivity analysis, and publication bias were conducted to
      measure the robustness of our findings. Using allele, recessive, dominant, and
      additive models, we did not reveal significant heterogeneity among 33 studies.
      Significant association of the SNCA rs11931074 polymorphism with PD was observed
      (T vs. G: OR = 1.36, 95% CI = 1.31-1.42; TT vs. TG + GG: OR = 1.58, 95% CI = 1.46
      1.72; TT + TG vs. GG: OR = 1.44, 95% CI = 1.35-1.55; TT vs. GG: OR = 1.87, 95% CI
      = 1.68-2.09) in the pooled populations. Furthermore, subgroup analyses accounting
      for ethnicity found similar significant results in both Asian and Caucasian
      populations. In conclusion, our meta-analysis further indicates that the SNCA
      rs11931074 polymorphism contributes to PD susceptibility. We believe that our
      findings will be very useful for future genetic studies on PD.

PMID- 30120621
TI  - Human Vestibulo-Ocular Reflex Adaptation: Consolidation Time Between Repeated
      Training Blocks Improves Retention.
AB  - We sought to determine if separating vestibulo-ocular reflex (VOR) adaptation
      training into training blocks with a consolidation (rest) period in between
      repetitions would result in improved VOR adaptation and retention. Consolidation
      of motor learning refers to the brain benefitting from a rest period after prior
      exposure to motor training. The role of consolidation on VOR adaptation is
      unknown, though clinicians often recommend rest periods as a part of vestibular
      rehabilitation. The VOR is the main gaze stabilising system during rapid head
      movements. The VOR is highly plastic and its gain (eye/head velocity) can be
      increased via training that induces an incrementally increasing retinal image
      slip error signal to drive VOR adaptation. The unilateral incremental adaptation
      technique typically consists of one 15-min training block leading to an increase
      in VOR gain of ~ 10 % towards the training side. We tested nine normal subjects,
      each over six separate sessions/days. Three training protocols/sessions were 5
      min each (1 * 5-min training) and three training protocols/sessions were 55 min
      each. Each 55-min protocol comprised 5-min training, 20-min rest, 5-min training,
      20-min rest, 5-min training (3 * 5-min training). Active and passive VOR gains
      were measured before and after training. For training with consolidation breaks,
      VOR gain retention was measured over 1 h. The VOR gain increase after 1 * 5-min
      training was 3.1 +/- 2.1 % (P < 0.01). One might expect that repeating this
      training three times would result in * 3 total increase of 9.3 %; however, the
      gain increase after 3 * 5-min training was only 7.1 +/- 2.8 % (P < 0.001),
      suggesting that consolidation did not improve VOR adaptation for our protocols.
      However, retention was improved by the addition of consolidation breaks, i.e.
      gains did not decrease over 1 h (P = 0.43). These data suggest that for optimal
      retention VOR adaptation exercises should be performed over shorter repeated
      blocks.

PMID- 30120624
TI  - Abnormal venous postural control: multiple sclerosis-specific change related to
      gray matter pathology or age-related neurodegenerative phenomena?
AB  - BACKGROUND: Autonomic nervous system dysfunction has been previously observed in
      multiple sclerosis (MS) patients. OBJECTIVE: To assess associations between
      magnetic resonance imaging-detected neuroinflammatory and neurodegenerative
      pathology and postural venous flow changes indicative of autonomic nervous system
      function. METHODS: We used a standardized 3T magnetic resonance imaging protocol
      to scan 138 patients with MS and 49 healthy controls. Lesion volume and brain
      volumes were assessed. The cerebral venous flow (CVF) was examined by color
      Doppler sonography in supine and upright positions and the difference was
      calculated as DeltaCVF. Based on DeltaCVF, subjects were split into absolute or
      quartile groups. Student's t test, chi2-test, and analysis of covariance adjusted
      for age and sex were used accordingly. Benjamini-Hochberg procedure corrected the
      p-values for multiple comparisons. RESULTS: No differences were found between
      healthy controls and patients with MS in both supine and upright Doppler-derived
      CVF, nor in prevalence of abnormal postural venous control. Patients with
      absolute negative DeltaCVF had higher disability scores (p = 0.013), lower gray
      matter (p = 0.039) and cortical (p = 0.044) volumes. The negative DeltaCVF MS
      group also showed numerically worse bladder/bowel function when compared to the
      positive DeltaCVF (2.3 vs. 1.5, p = 0.052). Similarly, the lowest quartile
      DeltaCVF MS group had higher T1-lesion volumes (p = 0.033), T2-lesion volumes (p
      = 0.032), and lower deep gray matter (p = 0.043) and thalamus (p = 0.033) volumes
      when compared to those with higher DeltaCVF quartiles. CONCLUSION: No difference
      in postural venous outflow between patients with MS and healthy controls was
      found. However, when the abnormal DeltaCVF is present within the MS population,
      it may be associated with more inflammatory and neurodegenerative pathology.
      Further studies should explore whether the orthostatic venous changes are an
      aging or an MS-related phenomenon and if the etiology is due to impaired
      autonomic nervous system functioning.

PMID- 30120625
TI  - Pluronic F127 blended polycaprolactone scaffolds via e-jetting for esophageal
      tissue engineering.
AB  - Several attempts have been made to fabricate esophageal tissue engineering
      scaffolds. However, most of these scaffolds possess randomly oriented fibres and
      uncontrollable pore sizes. In order to mimic the native esophageal tissue
      structure, electro-hydrodynamic jetting (e-jetting) was used in this study to
      fabricate scaffolds with aligned fibres and controlled pore size. A hydrophilic
      additive, Pluronic F127 (F127), was blended with polycaprolactone (PCL) to
      improve the wettability of the scaffolds and hence the cell adhesion. PCL/F127
      composite scaffolds with different weight ratios (0-12%) were fabricated. The
      wettability, phase composition, and the mechanical properties of the fabricated
      scaffolds were investigated. The results show that the e-jetted scaffolds have
      controllable fibres orientated in two perpendicular directions, which are similar
      to the human esophagus structure and suitable pore size for cell infiltration. In
      addition, the scaffolds with 8% F127 exhibited better wettability (contact angle
      of 14 degrees ) and an ultimate tensile strength (1.2 MPa) that mimics the native
      esophageal tissue. Furthermore, primary human esophageal fibroblasts were seeded
      on the e-jetted scaffolds. PCL/F127 scaffolds showed enhanced cell proliferation
      and expression of the vascular endothelial growth factor (VEGF) compared to
      pristine PCL scaffolds (1.5- and 25.8- fold increase, respectively; P < 0.001).
      An in vitro wound model made using the PCL/F127 scaffolds showed better cell
      migration than the PCL scaffolds. In summary, the PCL/F127 e-jetted scaffolds
      offer a promising strategy for the esophagus tissue repair.

PMID- 30120623
TI  - Enhancing Mitochondrial Health to Treat Hypertension.
AB  - PURPOSE OF REVIEW: This review summarizes literature pertaining to the dawning
      field of therapeutic targeting of mitochondria in hypertension and discusses the
      potential of these interventions to ameliorate hypertension-induced organ damage.
      RECENT FINDINGS: In recent years, mitochondrial dysfunction has been reported as
      an important contributor to the pathogenesis of hypertension-related renal,
      cardiac, and vascular disease. This in turn prompted development of novel
      mitochondria-targeted compounds, some of which have shown promising efficacy in
      experimental studies and safety in clinical trials. In addition, drugs that do
      not directly target mitochondria have shown remarkable benefits in preserving
      these organelles in experimental hypertension. Enhancing mitochondrial health is
      emerging as a novel feasible approach to treat hypertension. Future perspectives
      include mechanistic experimental studies to establish a cause-effect relationship
      between mitochondrial dysfunction and hypertension and further clinical trials to
      confirm the reno-, cardio-, and vasculo-protective properties of these compounds
      in hypertension.

PMID- 30120627
TI  - To stop or not to stop: a value of information view.

PMID- 30120626
TI  - Which Lipids Should Be Analyzed for Diagnostic Workup and Follow-up of Patients
      with Hyperlipidemias?
AB  - PURPOSE OF REVIEW: To summarize and discuss the clinical use of lipid and
      apolipoprotein tests in the settings of diagnosis and therapeutic follow-up of
      hyperlipidemia. RECENT FINDINGS: The joint consensus panel of the European
      Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry
      and Laboratory Medicine (EFLM) recently produced recommendations on the
      measurement of atherogenic lipoproteins, taking into account the strengths and
      weaknesses of analytical and clinical performances of the tests. Total
      cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non
      HDL cholesterol (= LDL + remnant cholesterol) constitute the primary lipid panel
      for hyperlipidemia diagnosis and cardiovascular risk estimation. LDL cholesterol
      is the primary target of lipid-lowering therapies. Non-HDL cholesterol or
      apolipoprotein B should be used as secondary therapeutic target in patients with
      mild-to-moderate hypertriglyceridemia, 2-10 mmol/l (175-880 mg/dl). Lipoprotein
      (a) is included in LDL cholesterol and should be measured at least once in all
      patients at cardiovascular risk, including to explain poor response to statin
      treatment.

PMID- 30120628
TI  - Assessment of the degradation rates and effectiveness of different coated Mg-Zn
      Ca alloy scaffolds for in vivo repair of critical-size bone defects.
AB  - Surgical repair of bone defects remains challenging, and the search for
      alternative procedures is ongoing. Devices made of Mg for bone repair have
      received much attention owing to their good biocompatibility and mechanical
      properties. We developed a new type of scaffold made of a Mg-Zn-Ca alloy with a
      shape that mimics cortical bone and can be filled with morselized bone. We
      evaluated its durability and efficacy in a rabbit ulna-defect model. Three types
      of scaffold-surface coating were evaluated: group A, no coating; group B, a 10
      MUm microarc oxidation coating; group C, a hydrothermal duplex composite coating;
      and group D, an empty-defect control. X-ray and micro-computed tomography(micro
      CT) images were acquired over 12 weeks to assess ulnar repair. A mechanical
      stress test indicated that bone repair within each group improved significantly
      over time (P < 0.01). The degradation behavior of the different scaffolds was
      assessed by micro-CT and quantified according to the amount of hydrogen gas
      generated; these measurements indicated that the group C scaffold better resisted
      corrosion than did the other scaffold types (P < 0.05). Calcein fluorescence and
      histology revealed that greater mineral densities and better bone responses were
      achieved for groups B and C than for group A, with group C providing the best
      response. In conclusion, our Mg-Zn-Ca-alloy scaffold effectively aided bone
      repair. The group C scaffold exhibited the best corrosion resistance and
      osteogenesis properties, making it a candidate scaffold for repair of bone
      defects.

PMID- 30120629
TI  - Modified Fe3O4 Magnetic Nanoparticle Delivery of CpG Inhibits Tumor Growth and
      Spontaneous Pulmonary Metastases to Enhance Immunotherapy.
AB  - As a novel toll-like receptor 9 (TLR9) agonist, synthetic unmethylated cytosine
      phosphate-guanine (CpG) oligodeoxynucleotides can stimulate a Th1 immune response
      and potentially be used as therapeutic agents or vaccine adjuvants for the
      treatment of cancer. However, some drawbacks of CpG limit their applications,
      such as rapid elimination by nuclease-mediated degradation and poor cellular
      uptake. Therefore, repeat high-dose drug administration is required for
      treatment. In this work, a CpG delivery system based on 3
      aminopropyltriethoxysilane (APTES)-modified Fe3O4 nanoparticles (FeNPs) was
      designed and studied for the first time to achieve better bioactivity of CpG. In
      our results, we designed FeNP-delivered CpG particles (FeNP/CpG) with a small
      average size of approximately 50 nm by loading CpG into FeNPs. The FeNP/CpG
      particle delivery system, with enhanced cell uptake of CpG in bone marrow-derived
      dendritic cells (BMDCs) in vitro and through intratumoral injection, showed
      significant antitumor ability by stimulating better humoral and cellular immune
      responses in C26 colon cancer and 4T1 breast cancer xenograft models in vivo over
      those of free CpG. Moreover, mice treated by FeNP/CpG particles had delayed tumor
      growth with an inhibitory rate as high as 94.4%. In addition, approximately 50%
      of the tumors in the C26 model appeared to regress completely. Similarly, there
      were lower pulmonary metastases and a 69% tumor inhibitory rate in the 4T1 breast
      cancer tumor model than those in the untreated controls. In addition to their
      effectiveness, the easy preparation, safety, and high stability of FeNP/CpG
      particles also make them an attractive antitumor immunotherapy.

PMID- 30120630
TI  - Effects of Tip Sonication Parameters on Liquid Phase Exfoliation of Graphite into
      Graphene Nanoplatelets.
AB  - Graphene nanoplatelets (GNPs) can be produced by exfoliating graphite in solvents
      via high-power tip sonication. In order to understand the influence of tip
      sonication parameters on graphite exfoliation to form GNPs, three typical flaked
      graphite samples were exfoliated into GNPs via tip sonication at power of 60,
      100, 200, or 300 W for 10, 30, 60, 90, 120, or 180 min. The concentration of GNP
      dispersions, the size and defect density of the produced GNPs, and the
      sedimentation behavior of GNP dispersions produced under various tip sonication
      parameters were determined. The results indicated that the concentration of the
      GNP dispersions was proportional to the square root of sonication energy input
      (the product of sonication power and time). The size and ID/IG values (determined
      by Raman spectrum) of GNPs produced under various tip sonication powers and times
      ranged from ~ 1 to ~ 3 MUm and ~ 0.1 to ~ 0.3, respectively, which indicated that
      all the produced GNPs were of high quality. The sedimentation behavior of GNP
      dispersions showed that the dispersions were favorably stable, and the
      concentration of each GNP dispersion was ~ 70% of its initial concentration after
      sedimentation for 96 h. Moreover, the TEM images and electron diffraction
      patterns were used to confirm that the produced GNPs were few-layer. This study
      has important implications for selecting the suitable tip sonicating parameters
      in exfoliating graphite into GNPs.

PMID- 30120631
TI  - Tips and tricks for rectal dissection during laparoscopic ultra-low anterior
      resection.

PMID- 30120632
TI  - Few-Layer Graphene Sheet-Passivated Porous Silicon Toward Excellent
      Electrochemical Double-Layer Supercapacitor Electrode.
AB  - Few-layer graphene sheet-passivated porous silicon (PSi) as an outstanding
      electrochemical double-layer supercapacitor electrode was demonstrated. The PSi
      matrix was formed by electrochemical etching of a doped silicon wafer and was
      further surface-passivated with few-layer graphene sheets by a Ni-assisted
      chemical vapor deposition process where a wide range of porous PSi structures,
      including mesoporous, macroporous, and hybrid porous structures were created
      during the graphene growth as temperature increases. The microstructural and
      graphene-passivation effects on the capacitive performance of the PSi were
      investigated in detail. The hybrid porous PSi electrode, optimized in terms of
      capacitive performances, achieves a high areal capacitance of 6.21 mF/cm2 at an
      ultra-high scan rate of 1000 mV/s and an unusual progressing cyclic stability of
      131% at 10,000 cycles. Besides mesopores and macropores, micropores were
      introduced onto the surfaces of the passivating few-layer graphene sheets with a
      KOH activation process to further increase the functioning surface area of the
      hierarchical porous PSi electrode, leading to a boost in the areal capacitance by
      31.4% up to 8.16 mF/cm2. The present designed hierarchical porous PSi-based
      supercapacitor proves to be a robust energy storage device for microelectronic
      applications that require stable high rate capability.

PMID- 30120633
TI  - Hippo signaling in the ovary and polycystic ovarian syndrome.
AB  - PURPOSE: To provide a commentary on our understanding of the role that the Hippo
      signaling pathway may play in patients with polycystic ovarian syndrome (PCOS)
      and how this understanding may impact the diagnosis of PCOS. METHODS: We assessed
      publications discussing the role of the Hippo signaling pathway in the ovary. In
      particular, we discuss how Hippo signaling disruption after ovarian
      fragmentation, combined with treating ovarian fragments with phosphatase and
      tensin homolog (PTEN) inhibitors and phosphoinositide-3-kinase stimulators to
      augment AKT signaling, has been used in treatment of patients with primary
      ovarian insufficiency. Furthermore, we discuss our own data on variations in
      Hippo signaling pathway gene expression in cumulus cells isolated from women
      undergoing IVF with a previous diagnosis of PCOS. RESULTS AND CONCLUSIONS:
      Aberrant Hippo signaling in PCOS patients is likely a contributing mechanism to
      the multifactorial etiology of the disease. Given the challenge of discerning the
      underlying etiology of oligo-ovulation in some patients, especially those with
      normal body mass indices, and the need for customized stimulation protocols for
      PCOS patients who have an increased risk of over-response and higher percentage
      of immature oocyte yield, it is important to identify these patients prior to
      treatment. Hippo gene expression fingerprints could potentially be used to more
      accurately define patients with PCOS. Additionally, targeting this pathway with
      pharmacologic agents could lead to non-surgical therapeutic options for PCOS.

PMID- 30120635
TI  - Correction to: Variability of Some Milk-Associated Genes and Proteins in Several
      Breeds of Saudi Arabian Camels.
AB  - The original version of this article contained mistakes in author names and
      affiliations. The last names of the authors Salah Korim, Amro Samra, and Hussein
      A. Amhedar were misspelled. The corrected spelling is Saleh A. Alkarim, Amr A. El
      Hanafy, and Hussein A. Almehdar. The correct list of author names and
      affiliations are published with this erratum.

PMID- 30120634
TI  - Mitochondrial DNA copy number in peripheral blood: a potential non-invasive
      biomarker for female subfertility.
AB  - PURPOSE: Low mitochondrial DNA (mtDNA) content in oocytes and in cumulus cells is
      an indicator of poor oocyte quality. Moreover, initial evidence showed a
      correlation between mtDNA content in cumulus cells and mtDNA copy number in
      peripheral blood cells. On these bases, we deemed of interest investigating the
      correlation between mtDNA copy number in peripheral blood and natural fecundity.
      METHODS: This is a nested case-control study drawn from a prospective cohort of
      pregnant women referred for routine first trimester screening for aneuploidies
      (from 11 + 0 to 12 + 6 weeks of gestation) between January 2012 and March 2013 at
      the "Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico" of Milan, Italy.
      Cases were subfertile women who attempted to become pregnant for 12-24 months.
      Controls were the two subsequently age-matched women who became pregnant in less
      than 1 year. MtDNA was quantified using real-time PCR and normalized to nuclear
      DNA. RESULTS: One hundred and four subfertile women and 208 controls were
      selected. The median (IQR) mtDNA copy number was 95 (73-124) and 145 (106-198),
      respectively (p < 0.001). The area under the ROC curve was 0.73 (95% CI 0.67
      0.79) (p < 0.001). The Youden index was 105 mtDNA copy number. The crude OR for
      subfertility in women with mtDNA copy number below this threshold was 5.72 (95%
      CI 3.43-9.55). The accuracy of mtDNA copy number assessment in peripheral blood
      progressively decreased with increasing female age. CONCLUSIONS: Low mtDNA copy
      number in peripheral blood is associated with an increased risk of subfertility
      and may represent a biomarker of natural fecundity.

PMID- 30120637
TI  - Access to Treatment for Alcohol Use Disorder at US Health Centers: a National
      Study.

PMID- 30120636
TI  - Examining the Interrelations Among Objective and Subjective Health Literacy and
      Numeracy and Their Associations with Health Knowledge.
AB  - BACKGROUND: Health literacy and numeracy influence many health-related behaviors
      and outcomes. Health literacy and numeracy have been assessed objectively and
      subjectively, but interrelationships among the measures and the consistency of
      their association with health knowledge have not been examined. OBJECTIVE: To
      increase understanding of the structure and interrelations among objective and
      subjective health literacy and numeracy and how these constructs relate to
      knowledge of risk factors of two major diseases. DESIGN: Secondary analysis of
      cross-sectional survey data, weighted to be representative of the general US
      population of non-institutionalized adults. PARTICIPANTS: Participants (N = 1005,
      55.2% response rate) were recruited from GfK KnowledgePanel. The unweighted
      sample included 52% women, 26% racial/ethnic minorities, and 37% with no college
      experience. MAIN MEASURES: Objective health literacy, subjective health literacy,
      objective numeracy, subjective numeracy. Objective and perceived knowledge of
      diabetes and colon cancer risk factors were also assessed. KEY RESULTS:
      Confirmatory factor analyses indicated that a model with correlated (r = 0.16
      0.56) but separate factors for each of the four literacy/numeracy constructs best
      fit the data (RMSEA = 0.055 (95% CI 0.049-0.061), CFI = 0.94). Consistency
      between measures in classifying people as having adequate or limited health
      literacy or numeracy was 60.9-77.1%, depending on the combination of measures.
      All four literacy/numeracy constructs were independently associated with
      objective diabetes knowledge and objective colon cancer knowledge (all ps < .04).
      Subjective (but not objective) literacy and numeracy measures were associated
      with diabetes perceived knowledge (all ps < .02). No literacy/numeracy measures
      were associated with perceived colon cancer knowledge. CONCLUSIONS: We identified
      objective and subjective health literacy and numeracy as four distinct but
      related concepts. We also found that each construct accounts for unique variance
      in objective (but not subjective) disease knowledge. Until research uncovers what
      psychological processes drive subjective measures (e.g., motivation, self
      efficacy), research investigating the relationship between health literacy and
      health outcomes should consider assessing all four measures.

PMID- 30120638
TI  - The loading patterns of a short femoral stem in total hip arthroplasty: gait
      analysis at increasing walking speeds and inclines.
AB  - BACKGROUND: The purpose of this study was to examine the gait pattern of total
      hip arthroplasty (THA) patients with a new short femoral stem at different speeds
      and inclinations. MATERIALS AND METHODS: A total of 40 unilateral THA patients
      were tested on an instrumented treadmill. They comprised two groups (shorter
      stemmed THA n = 20, longer stemmed THA n = 20), both which had the same surgical
      posterior approach. The shorter femoral stemmed patients were taken from an
      ongoing hip trial with minimum 12 months postop. The comparative longer THR group
      with similar disease and severity were taken from a gait database along with a
      demographically similar group of healthy controls (n = 35). All subjects were
      tested through their entire range of gait speeds and inclines with ground
      reaction forces collected. Body weight scaling was applied and a symmetry index
      to compare the implanted hip to the contralateral normal hip. An analysis of
      variance with significance set at alpha = 0.05 was used. RESULTS: The
      experimental groups were matched demographically and implant groups for patient
      reported outcome measures and radiological disease. Both THA groups walked slower
      than controls, but symmetry at all intervals for all groups were not
      significantly different. Push-off loading was less favourable for both the
      shorter and longer stemmed THR groups (p < 0.05) depending on speed. CONCLUSIONS:
      Irrespective of femoral stem length, symmetry for ground reaction forces for both
      THA groups were returned to a normal range when compared to controls. However
      individual implant performance showed inferior (p < 0.05) push-off forces and
      normalised step length in both THR groups when compared to controls. LEVEL OF
      EVIDENCE: III.

PMID- 30120639
TI  - The anxiolytic effects of atorvastatin and simvastatin on dietary-induced
      increase in homocysteine levels in rats.
AB  - The aim of this study was to evaluate the effects of atorvastatin and simvastatin
      on behavioral manifestations that followed hyperhomocysteinemia induced by
      special dietary protocols enriched in methionine and deficient in B vitamins (B6,
      B9, B12) by means of alterations in anxiety levels in rats. Simultaneously, we
      investigated the alterations of oxidative stress markers in rat hippocampus
      induced by applied dietary protocols. Furthermore, considering the well-known
      antioxidant properties of statins, we attempted to assess their impact on major
      markers of oxidative stress and their possible beneficial role on anxiety-like
      behavior effect in rats. The 4-week-old male Wistar albino rats were divided
      (eight per group) according to basic dietary protocols: standard chow, methionine
      enriched, and methionine-enriched vitamins B (B6, B9, B12) deficient. Each
      dietary protocol (30 days) included groups with atorvastatin (3 mg/kg/day i.p.)
      and simvastatin (5 mg/kg/day i.p.). The behavioral testing was performed in the
      open field and elevated plus maze tests. Parameters of oxidative stress (index of
      lipid peroxidation, superoxide dismutase, catalase activity, glutathione) were
      determined in hippocampal tissue samples following decapitation after anesthesia.
      Methionine-load dietary protocols induced increased oxidative stress in rat
      hippocampus, which was accompanied by anxiogenic behavioral manifestations. The
      methionine-enriched diet with restricted vitamins B intake induced more
      pronounced anxiogenic effect, as well as increased oxidative stress compared to
      the methionine-load diet with normal vitamins B content. Simultaneous
      administration of statins showed beneficial effects by means of both decreased
      parameters of oxidative stress and attenuation of anxiety. The results obtained
      with simvastatin were more convincible compared to atorvastatin.

PMID- 30120640
TI  - EUS-Guided Intragastric Injection of Botulinum Toxin A in the Preoperative
      Treatment of Super-Obese Patients: a Randomized Clinical Trial.
AB  - BACKGROUND: Obesity is a disease that is highly prevalent in Brazil, and the
      associated comorbidities represent a major global public health challenge.
      Botulinum toxin type A (BTX-A) is a potent neurotoxin and inhibitor of gastric
      smooth muscle activity. In theory, BTX-A administration should promote early
      satiety and weight loss because it delays gastric emptying by inhibiting
      acetylcholine-mediated peristalsis, which is primarily responsible for gastric
      motility. Because results in the literature are discrepant, the efficacy of
      intragastric injections of BTX-A as a primary treatment for obesity remains
      unknown. The objective of this prospective, double-blind, single-center
      randomized study was to evaluate the effects of endoscopic ultrasound-guided
      intragastric BTX-A injections, as a bridge to bariatric surgery, in super-obese
      patients. METHODS: Thirty-two super-obese patients were randomized to one of two
      groups: BTX-A, in which 200 units of BTX-A were injected into the gastric antrum
      and body; and control, in which the same injections were performed with 0.9%
      saline. Weight, body mass index (BMI), and loss of excess weight were measured
      monthly over a 6-month period. Gastric emptying scintigraphy was performed before
      and after the procedure. RESULTS: The patients in both groups showed significant
      weight loss over the course of the study (p < 0.001). There were no statistically
      significant differences between the groups regarding weight loss, excess weight,
      total loss of excess weight, total weight loss, or change in BMI. CONCLUSIONS:
      Intragastric injection of BTX-A does not appear to be an effective method of
      achieving preoperative weight loss in super-obese patients.

PMID- 30120641
TI  - Does Bariatric Surgery Cause Vitamin A, B1, C or E Deficiency? A Systematic
      Review.
AB  - BACKGROUND: The restrictive and/or malabsorptive nature of bariatric surgery may
      increase the risk for micronutrient deficiencies. This systematic review aimed to
      identify and critique the evidence for vitamin A, B1, C or E deficiencies
      associated with bariatric surgery. METHODS: This review utilised PRISMA and MOOSE
      frameworks with NHMRC evidence hierarchy and the American Dietetic Association
      bias tool to assess the quality of articles. RESULTS: Twenty-one articles were
      included and once critiqued all studies were of level IV grade and neutral or
      negative in quality. The relevance of measuring micronutrient supplementation and
      inflammatory markers for validity of serum vitamins is absent within the
      literature. CONCLUSIONS: Future research is needed to investigate the risk of
      deficiency for these procedures with focus on confounders to serum
      micronutrients.

PMID- 30120642
TI  - Intersectional nativity and racial/ethnic disparities in human papillomavirus
      vaccination initiation among U.S. women: a national population-based study.
AB  - BACKGROUND: Overall, foreign-born women are less likely than U.S.-born women to
      have initiated human papillomavirus (HPV) vaccination. However, foreign-born
      women are a racially/ethnically diverse population, and race/ethnicity is an
      independent predictor of HPV vaccination. METHODS: Using 2011-2015 National
      Health Interview Survey data, we used multivariable logistic regression to
      estimate odds ratios for foreign-born black, Latina, and Asian women compared to
      foreign-born white women and U.S.-born white women, adjusting for
      sociodemographic factors. We added socioeconomic factors followed by health care
      access indicators, which we conceptualized as potential mediators, to each model
      to assess whether they helped explain observed disparities. RESULTS: Foreign-born
      Asian ([odds ratio=] 0.43; [95% confidence interval:] 0.29-0.65) and Latina
      (0.46; 0.32-0.68) women had significantly lower adjusted odds of initiating HPV
      vaccination compared to foreign-born white women. Foreign-born white (0.64; 0.45
      0.90), black (0.44; 0.29, 0.67), Latina (0.29; 0.24-0.35), and Asian (0.28; 0.21
      0.38) women had significantly lower adjusted odds of HPV vaccination initiation
      compared to U.S.-born white women. Socioeconomic factors only explained HPV
      vaccination initiation disparities between foreign-born Latina women and foreign
      born and U.S.-born white women. Health care access indicators modestly explained
      disparities between foreign-born white, black, and Latina women and U.S.-born
      white women only. CONCLUSIONS: We observed pronounced HPV vaccination initiation
      disparities among foreign-born women in relation to race/ethnicity and between
      foreign-born women from minoritized racial/ethnic backgrounds and U.S.-born white
      women. Research on nativity disparities in HPV vaccination should take into
      account race/ethnicity, and vice versa. Interventions that seek to facilitate HPV
      vaccination among foreign-born women are needed and should address the unique
      needs of those from minoritized racial/ethnic backgrounds to promote cancer
      equity.

PMID- 30120643
TI  - Sleep apnea and subsequent cancer incidence.
AB  - PURPOSE: In vitro and animal models suggest that the physiological effects of
      sleep apnea could contribute to cancer risk, yet epidemiologic studies have been
      inconsistent. METHODS: We identified a cohort of adults diagnosed with sleep
      apnea between 2005 and 2014 using regional administrative databases. Linking this
      cohort to a population-based cancer registry, we identified first incident
      cancers diagnosed after sleep apnea diagnosis through 2015. We calculated age-sex
      standardized cancer incidence ratios (SIRs) to compare the observed number of
      cancers among those with sleep apnea with expected population estimates over a
      comparable period. RESULTS: Among 34,402 individuals with sleep apnea, 1,575
      first incident cancers were diagnosed during follow-up (mean +/- SD; 5.3 +/- 2.0
      years). Compared to the general population, cancer incidence (SIR 1.26, 95% CI
      1.20-1.32) was elevated among sleep apnea patients. We observed significantly
      elevated incidence for kidney (SIR 2.24, 95% CI 1.82-2.72), melanoma (SIR 1.71,
      95% CI 1.42-2.03), breast (SIR 1.43, 95% CI 1.76-2.00), and corpus uteri (SIR
      2.80, 95% CI 2.24-2.47) while risk for lung (SIR 0.66, 95% CI 0.54-0.79) and
      colorectal cancer (SIR 0.71, 95% CI 0.56-0.89) was lower. CONCLUSION: These
      findings suggest an elevated cancer burden, particularly at certain sites, among
      individuals with diagnosed sleep apnea. Results should be interpreted with
      caution due to unmeasured confounders (e.g., BMI, diabetes).

PMID- 30120645
TI  - Mining of Egypt's Red Sea invertebrates for potential bioactive producers.
AB  - OBJECTIVE: The objective of this work was to isolate bacteria from Red Sea
      invertebrates, determine their antimicrobial activity, and screen for the
      biosynthetic gene clusters [polyketides (PKs) and nonribosomal peptides (NRPs)]
      which could be involved in the production of bioactive secondary metabolites.
      RESULT: Eleven different samples of marine invertebrates' were collected from
      Egypt's Red Sea (El-Tor-Sharm El-Sheikh and Hurghada) by scuba diving, and a
      total 80 isolates of the associated microorganisms were obtained from the
      cultivation on six different cultural medium. Seven isolates of them showed an
      antimicrobial activity against five pathogenic reference strains, while the most
      active antimicrobial agent was isolate number HFF-8 which was 99% identical to
      Bacillus amyloliquefaciens. HFF-8's extract showed positive results against Gram
      negative bacteria, Gram positive bacteria and yeast. Moreover, the isolates gave
      positive bands when screened for the presence of PK synthase (PKS) I and II and
      NRP synthetase (NRPS) I and II biosynthetic genes, those biosynthetic fragments
      when cloned and sequenced were primitively predicted as biosynthetic fragments
      for kirromycin and leinamycin production by NaPDoS program with 56 and 55%,
      respectively. CONCLUSION: The Red Sea can provide a sustainable solution to
      combat bacterial resistance. The contribution of this work is that B.
      amyloliquefaciens was isolated from Heteroxenia fuscescens, Red Sea, Egypt.
      Moreover, the bacterial extract showed a broad spectrum with a potent
      antimicrobial activity.

PMID- 30120646
TI  - Outcomes of Clostridium difficile-suspected diarrhea in a French university
      hospital.
AB  - Clostridium difficile infection (CDI) produces a variety of clinical
      presentations ranging from mild diarrhea to severe infection with fulminant
      colitis, septic shock, and death. CDI puts a heavy burden on healthcare systems
      due to increased morbidity and mortality, and higher costs. We evaluated the
      clinical impact of CDI in terms of complications and mortality in a French
      university hospital compared with patients with diarrhea unrelated to CDI. A 3
      year prospective, observational, cohort study was conducted in a French
      university hospital. Inpatients aged 18 years or older with CDI-suspected
      diarrhea were eligible to participate in the study and were followed for up to 60
      days after CDI testing. Among the 945 patients with diarrhea included, 233 had
      confirmed CDI. Overall, 106 patients (11.2%) developed at least one of the
      following complications: colectomy, colitis, ileitis/rectitis, ileus, intestinal
      perforation, megacolon, multiorgan failure, pancolitis, peritonitis,
      pseudomembranous colitis, renal failure, and sepsis/septic shock. The
      complication rate was significantly higher in patients with diarrhea related to
      C. difficile than in non-CDI patients (26.6% vs 6.2%, P < 0.001). At day 60, 137
      (14.5%) patients had died, with 37 deaths among the CDI group (15.9%). Death was
      attributable to CDI in 15 patients (6.4%). Complications are more frequent among
      CDI cases than in patients with diarrhea not related to C. difficile. Assessment
      of CDI is necessary to ensure allocation of sufficient resources to CDI
      prevention.

PMID- 30120647
TI  - An evaluation of risk factors to predict target concentration non-attainment in
      critically ill patients prior to empiric beta-lactam therapy.
AB  - To determine whether target concentration non-attainment can be anticipated in
      critically ill patients prior to initiating empiric beta-lactam antibiotic
      therapy based on readily available clinical factors. Retrospective review of
      consecutive patients treated with piperacillin or meropenem and who underwent
      therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia)
      between January 2013 and December 2015 was performed. Predefined subgroups were
      patients who received continuous renal replacement therapy (CRRT) and those who
      did not (non-CRRT). Potential risk factors were evaluated by correlation with
      beta-lactam antibiotic trough concentrations (Cmin) lower than or equal to
      targeted minimum inhibitory concentration (MIC). Only the first drug
      concentration after initiation of the antibiotic treatment was included to
      reflect empirical dose selection. A total of n = 249 patients (piperacillin, n =
      169; meropenem, n = 80) were investigated. For non-CRRT patients (n = 210),
      multivariate analysis demonstrated the following: male gender (p = 0.006);
      younger age (p = 0.015); prescribed daily antibiotic dose less than 1.5 times the
      product information recommendations (p = 0.004); lack of positive microbiology (p
      = 0.006); lower overall illness severity (p = 0.005); and estimated glomerular
      filtration rate (eGFR) >= 90 mL/min/1.73 m2 (p < 0.001), to be associated with
      Cmin <= MIC. No predictor variable was found to be significantly associated with
      Cmin <= MIC for the CRRT cohort. Evaluating the risk of target concentration non
      attainment using simple clinical factors is possible at the bedside for non-CRRT
      patients prior to empiric antibiotic initiation. Clinicians should be wary of
      selecting doses based on the product information especially when treating younger
      male patients with apparently 'normal' renal function.

PMID- 30120644
TI  - Metabolic and Molecular Imaging with Hyperpolarised Tracers.
AB  - Since reaching the clinic, magnetic resonance imaging (MRI) has become an
      irreplaceable radiological tool because of the macroscopic information it
      provides across almost all organs and soft tissues within the human body, all
      without the need for ionising radiation. The sensitivity of MR, however, is too
      low to take full advantage of the rich chemical information contained in the MR
      signal. Hyperpolarisation techniques have recently emerged as methods to overcome
      the sensitivity limitations by enhancing the MR signal by many orders of
      magnitude compared to the thermal equilibrium, enabling a new class of metabolic
      and molecular X-nuclei based MR tracers capable of reporting on metabolic
      processes at the cellular level. These hyperpolarised (HP) tracers have the
      potential to elucidate the complex metabolic processes of many organs and
      pathologies, with studies so far focusing on the fields of oncology and
      cardiology. This review presents an overview of hyperpolarisation techniques that
      appear most promising for clinical use today, such as dissolution dynamic nuclear
      polarisation (d-DNP), parahydrogen-induced hyperpolarisation (PHIP), Brute force
      hyperpolarisation and spin-exchange optical pumping (SEOP), before discussing
      methods for tracer detection, emerging metabolic tracers and applications and
      progress in preclinical and clinical application.

PMID- 30120649
TI  - Assessment of patients post reversal with idarucizumab.
AB  - Idarucizumab, a fully humanized Fab antibody fragment, is indicated for reversal
      of dabigatran's anticoagulant activity. Idarucizumab neutralizes the
      anticoagulant effects of dabigatran by binding to dabigatran and its metabolite.
      In the full analysis of 503 patients, idarucizumab fully reversed the
      anticoagulant effect of dabigatran in more than 98% of patients. Real-world
      clinical experience with idarucizumab for dabigatran reversal remains limited. We
      report 11 real-world clinical cases in which idarucizumab was administered for
      dabigatran reversal in the setting of bleed (bleeding cohort n = 5) or emergent
      procedure (emergent procedure cohort, n = 6). Coagulation tests and clinical
      outcomes were assessed before and after idarucizumab administration. Clinical
      outcomes included thromboembolic events and hemostasis. The median (IQR) aPTT
      (seconds) before versus after idarucizumab was 40.4 (36.1) versus 27.3 (6.2)
      (bleeding cohort) and 50.1 (13.4) versus 26.5 (8.1) (emergent procedure cohort).
      The median (IQR) INR before and after idarucizumab was 2.0 (1.1) versus 1.2 (0.1)
      (bleeding cohort) and 1.1 (0.5) versus 1.1 (0.3) (emergent procedure cohort).
      Hemostasis was achieved in 4/5 patients in the bleeding cohort and 5/6 patients
      in the emergent procedure cohort. Thrombotic events occurred in four patients
      with a median time (IQR) from idarucizumab administration of 7.4 (4.3-14.7) days.
      Idarucizumab achieved adequate dabigatran reversal as evident by normalization of
      aPTT, INR, and achieving hemostasis. However, our data demonstrates a high
      thrombotic risk associated with dabigatran reversal with idarucizumab than
      previously reported.

PMID- 30120648
TI  - Prevalence and risk factors of post chikungunya rheumatic musculoskeletal
      disorders: a prospective follow-up study in French Guiana.
AB  - The estimated seroprevalence in the general population after chikungunya virus
      (CHIKV) epidemics ranged from 38 to 63%. Despite a low case fatality, subacute
      and chronic rheumatic forms of CHIKV infection generate significant morbidity and
      have a socioeconomic impact. The objective of the study was to estimate the
      prevalence of chronic post-CHIKV rheumatic or musculoskeletal pain (pCHIK-RMSP)
      at 3 and 6 months after the initial symptoms. An observational study was
      conducted at Cayenne General Hospital in French Guiana between April 1 and June
      30, 2014. All patients seen for CHIKV infection confirmed by RT-PCR were
      prospectively included. Pregnant women and children under 15 were excluded from
      the study. All patients were called by phone at 3 and 6 months to enquire about
      the presence of pCHIK-RMSP. Out of a total of 254 eligible patients, 168 were
      selected. The mean age was 45.3 years (SD +/- 1.4 yo) and the sex ratio (M/F) was
      0.75. No death was reported. At 3 months, 40.2% (95% CI 31.1-49.3) of patients (n
      = 45/112) had pCHIK-RMSP and 31.3% (95% CI 22.2-40.4) of patients (n = 31/99) at
      6 months. The median time of end to pain was 2 weeks after the date of onset of
      signs. The present study provides succinct but informative data about pCHIK-RMSP,
      which represents the real burden of the disease. There are few studies on that
      subject in the Amazonian region, but our study shows a lower impact than in the
      Indian Ocean islands where the population is older.

PMID- 30120651
TI  - ENO2 knock-out mutants in Arabidopsis modify the regulation of the gene
      expression response to NaCl stress.
AB  - There is a growing awareness that some dual-function enzymes may provide a
      directly evidence that metabolism could feed into the regulation of gene
      expression via metabolic enzymes. However, the mechanism by which metabolic
      enzymes control gene expression to optimize plant stress responses remains
      largely unknown in Arabidopsis thaliana. LOS2/ENO2 is a bifunctional gene
      transcribed a functional RNA that translates a full-length version of the ENO2
      protein and a truncated version of the MBP-1 protein. Here, we report that eno2
      negatively regulates plant tolerance to salinity stress. NaCl treatment caused
      the death of the mutant eno2/eno2 homozygote earlier than the wild type (WT)
      Arabidopsis. To understand the mechanism by which the mutant eno2 had a lower
      NaCl tolerance, an analysis of the expressed sequence tag (EST) dataset from the
      WT and mutant eno2 Arabidopsis was conducted. Firstly, the most identified up-
      and down-regulated genes are senescence-associated gene 12 (SAG12) and
      isochorismate mutase-related gene, which are associated with salicylic acid (SA)
      inducible plant senescence and endogenous SA synthesis, respectively. Secondly,
      the differentially regulated by salt stress genes in mutant eno2 are largely
      enriched Gene Ontology(GO) terms associated with various kinds of response to
      stimulations. Thirdly, in the Kyoto Encyclopedia of Genes and Genomes (KEGG)
      mapping, we find that knocking out ENO2-influenced genes were most enriched into
      metabolite synthesis with extra plant-pathogen interaction pathway and plant
      hormone signal transduction pathway. Briefly, with the translation shifting
      function, LOS2/ENO2 not only influenced the genes involved in SA synthesis and
      transduction, but also influenced genes that participate in metabolite synthesis
      in cytoplasm and gene expression variation in nuclear under salt stress.

PMID- 30120650
TI  - Bivalirudin for left ventricular assist device thrombosis.
AB  - Pump thrombosis remains a serious complication of implantable ventricular assist
      device therapy and is associated with increased risk of morbidity and mortality.
      Optimal management strategies remain controversial and are guided largely by
      limited literature and expert opinion. Medical management of pump thrombosis,
      including the use of direct thrombin inhibitors, has been associated with mixed
      results. The purpose of this study is to report the outcomes associated with
      bivalirudin therapy in LVAD patients with suspected pump thrombosis. A single
      center, retrospective observational study of 15 patients with suspected pump
      thrombosis that were all treated with bivalirudin therapy was conducted. The
      majority of subjects' initial treatment courses were unsuccessful [9/15 (60%)];
      however, 6/15 (40%) achieved an initial improvement in serum lactate
      dehydrogenase (LDH) levels and were stabilized to be successfully discharged from
      the hospital. Of the subjects discharged, there was a high rate of recurrence of
      pump thrombosis within 6 months [5/6 (83.3%)]. Bivalirudin therapy was not
      associated with a consistent reduction in LDH among all subjects studied, and
      clinical responses to therapy appear to be associated with high rates of
      thrombosis recurrence. This study analyzes the largest cohort to date of LVAD
      patients with pump thrombosis treated with bivalirudin therapy, and suggests that
      alternative therapies should be considered in management.

PMID- 30120652
TI  - ZNF143 is a regulator of chromatin loop.
AB  - It is known that transcription factor ZNF143 frequently co-binds with CTCF
      Cohesin complex in the anchor regions of chromatin loops. However, there is
      currently no genome-wide experiment to explore the functional roles of ZNF143 in
      chromatin loops. In this work, we used both computational and experimental
      analyses to investigate the regulatory effect of ZNF143 on chromatin loops. By
      jointly analyzing the ZNF143 and CTCF motifs underlying the isolated ZNF143
      binding sites, ZNF143-CTCF co-binding sites and ZNF143-CTCF-RAD21 co-binding
      sites, our result shows that the ZNF143-CTCF-RAD21 co-binding sites are enriched
      with CTCF motifs but depleted of Znf143 motifs, implying that the CTCF but not
      ZNF143 may directly binds to the genome and thus ZNF143 may act as a cofactor
      instead of pioneer factor of ZNF143-CTCF-Cohesin complex. To explore the
      regulatory effect of ZNF143 on chromatin loops, we conducted siRNA experiment to
      knock down the expression level of ZNF143 in HEK293T cell line, and then
      performed in situ Hi-C on the negative control and ZNF143-silenced HEK293T cells.
      Comparison shows that the majority of chromatin loops are lost or at least
      weakened in the ZNF143-silenced HEK293T cells. However, a small proportion of
      chromatin loops are gained or strengthened, indicating the complicated roles of
      ZNF143 reduction in regulating chromatin loops. To further validate the loop
      analyses, we thoroughly investigated the chromatin loop changes between negative
      control and ZNF143-silenced cells by using aggregate peak analysis. The
      calculation shows that the lost and gained chromatin loops do undergo loop
      strength changes after ZNF143 silencing. Altogether, our work shows that ZNF143
      can regulate chromatin loops by acting as a cofactor of CTCF-Cohesin complex, and
      knocking down ZNF143 expression level mainly eliminates or destabilizes chromatin
      loops.

PMID- 30120654
TI  - Pirfenidone Ointment Modulates the Burn Wound Bed in C57BL/6 Mice by Suppressing
      Inflammatory Responses.
AB  - An inflammatory response is the normal response to a burn-induced injury. The
      burn-associated inflammation can lead to further tissue damage as the tissue
      tries to repair the damage. Prolonged or excessive inflammation is associated
      with increased fibrosis of burn wounds and the development of hypertrophic scars.
      The high incidence of hypertrophic scar formation is one of the many challenges
      to treating deep partial-thickness burns. Prophylactic treatment to improve burn
      induced hypertrophic scarring is lacking. For this reason, we evaluated
      prophylactic treatment of deep partial-thickness burns with pirfenidone in
      C57BL/6 mice. Pirfenidone is an FDA-approved anti-fibrotic drug for systemic use
      in the treatment of idiopathic lung fibrosis and other fibrotic disorders.
      Additionally, pirfenidone has anti-inflammatory activity. We tested treatment
      efficacy of pirfenidone using a mouse model of deep partial-thickness burns.
      Inflammatory cytokines including IL-1beta, IL-2, IL-6, IL-13, G-CSF, and MIP
      1alpha, along with neutrophil infiltration, were significantly reduced in wounds
      when mice were treated during the inflammatory phase of burn wound healing.
      Additionally, pirfenidone significantly reduced expression of alphaSMA 12 days
      after the induction of burns and modestly reduced hydroxyproline in 22-day-old
      burn wounds. Results show that pirfenidone treatment modulated the inflammatory
      response of the burn wound. The findings in this study indicate that further
      examination is required to validate the use of pirfenidone for prophylactic
      treatment to improve long-term outcomes of scarring and contracture in deep
      partial-thickness burn wounds.

PMID- 30120655
TI  - Polyphyllin I Inhibits Propionibacterium acnes-Induced Inflammation In Vitro.
AB  - Propionibacterium acnes (P. acnes) has been implicated in the progression of acne
      inflammation. Because current acne medications have various side effects, it is
      necessary to explore alternative medications possessing anti-inflammatory
      activity against P. acnes. We investigated the inhibitory effects of polyphyllin
      I (PPI) on P. acnes-induced inflammation in vitro. In this study, we examined the
      effects of PPI on the production of inflammatory cytokines in HaCaT keratinocytes
      treated with heat-killed P. acnes. These treated HaCaT keratinocytes showed
      increased expression of Toll-like receptor 2 (TLR2) and production of
      inflammatory cytokines. PPI significantly suppressed the secretion of
      inflammatory cytokines, including interleukin (IL)-6, IL-8, and tumor necrosis
      factor (TNF)-alpha, and the expression of TLR2 in P. acnes-treated cells.
      Moreover, we studied the influence of PPI on the nuclear factor-kappaB (NF
      kappaB) and mitogen-activated protein kinase (MAPK) signaling pathways in P.
      acnes-treated keratinocytes. PPI diminished the activation of NF-kappaB.
      Phosphorylated p38 levels were markedly increased after treatment with heat
      killed P. acnes but were decreased after treatment with PPI, while the effect of
      PPI on ERK phosphorylation was not significant. Heat-killed P. acnes and PPI did
      not have any effect on JNK phosphorylation. Furthermore, we confirmed that NF
      kappaB p65 inhibitor (BAY11-7082), p38 MAPK inhibitor (SB203580), and PPI blocked
      the expression of IL-8 in heat-killed P. acnes-treated cells. These results
      demonstrated that PPI has potential for development as a treatment for acne
      inflammation.

PMID- 30120653
TI  - Tolfenamic Acid Attenuates 3-Nitropropionic Acid-Induced Biochemical Alteration
      in Mice.
AB  - Tolfenamic acid (TA), a nonsteroidal anti-inflammatory drug, shows
      neuroprotective effects and alleviates cognitive deficits in transgenic mouse
      models of Alzheimer's disease. However, whether TA can prevent the biochemical
      alterations induced by intraperitoneal injection of 3-nitropropionic acid (3-NP)
      in mice is still unknown. In this study, the striatal lesion area was measured by
      2,3,5-triphenyltetrazolium chloride staining. Glutamate, SDH and ATP levels were
      tested using colorimetric assay kits. The neuroinflammatory cytokine levels were
      tested by ELISA kits. The expression of synaptic proteins and the subtypes of the
      NMDA receptor were tested by western blotting. TA was orally administered 10 days
      before 3-NP injection (pretreatment) or on the same day as 3-NP injection (co
      treatment). TA pretreatment showed the strongest neuroprotective effects:
      pretreatment significantly attenuated the 3-NP-induced muscular weakness in the
      forelimb and alterations in glutamate level, mitochondrial function, and pro
      inflammatory cytokine release in the brains of mice. These results suggest that
      TA has preventive and protective effects on 3-NP-induced neurotoxicity.

PMID- 30120656
TI  - InCl3-catalyzed one-pot synthesis of multi-substituted pyrano[2,3-c]pyrazole-4
      carboxylic acid esters under ultrasound irradiation.
AB  - An efficient and simple procedure for the synthesis of 6-amino-5-cyano-4-phenyl
      pyrano[2,3-c]pyrazole-4-carboxylic acid esters was developed via a one-pot
      reaction of beta-ketoester, hydrazine, benzoylacetate, and malononitrile in 50%
      EtOH catalyzed by InCl3 under ultrasound irradiation. This method is more
      economic, convenient, nontoxic, and environmentally friendly than established
      methods of pyranopyrazole synthesis. Target compounds were obtained in excellent
      yields of up to 95%.

PMID- 30120657
TI  - New insights into the selective inhibition of the beta-carbonic anhydrases of
      pathogenic bacteria Burkholderia pseudomallei and Francisella tularensis: a
      proteochemometrics study.
AB  - Nowadays, antibiotic resistance has turned into one of the most important
      worldwide health problems. Biological end point of critical enzymes induced by
      potent inhibitors is recently being considered as a highly effective and popular
      strategy to defeat antibiotic-resistant pathogens. For instance, the simple but
      critical beta-carbonic anhydrase has recently been in the center of attention for
      anti-pathogen drug discoveries. However, no beta-carbonic anhydrase selective
      inhibitor has yet been developed. Available beta-carbonic anhydrase inhibitors
      are also highly potent with regard to human carbonic anhydrases, leading to
      severe inevitable side effects in case of usage. Therefore, developing novel
      inhibitors with high selectivity against pathogenic beta-carbonic anhydrases is
      of great essence. Herein, for the first time, we have conducted a
      proteochemometric study to explore the structural and the chemical aspects of the
      interactions governed by bacterial beta-carbonic anhydrases and their inhibitors.
      We have found valuable information which can lead to designing novel inhibitors
      with better selectivity for bacterial beta-carbonic anhydrases.

PMID- 30120658
TI  - The Impact of Priming on Speed Reduction on a Ski Slope.
AB  - We tested a field-adapted priming procedure (a technique used to subtly activate
      mental representations and guide behavior) on a ski slope, with the goal of
      reducing risk behavior in winter sports. At cableway stations, skiers were
      initially exposed eight times to a prevention poster displaying a logo and a
      "slow down" message. The "slow down" concept was activated on the ski slope by
      exposing skiers (or not) 10 times to the logo featured on the poster. We used a
      radar device to measure the skiers' speed data just before a slope intersection.
      We hypothesized that the mean speed would be lower in the presence of the logo
      than in its absence. As predicted, the speed was lower (by 0.9 km/h) when the
      skiers had been primed (i.e., exposed to the logo). This decrease was relevant,
      since any reduction in speed downhill will reduce kinetic (impact) energy and
      thus the risk of injury in a collision. The effect of priming was statistically
      significant at noon and in the afternoon but not in the morning. Our pilot study
      is the first to show that a priming procedure can influence the speed of skiers
      at a dangerous location. Our findings open up new perspectives for the prevention
      of risk behavior in winter sports.

PMID- 30120659
TI  - Response of Zea mays to multimetal contaminated soils: a multibiomarker approach.
AB  - Heavy metals present in mine tailings pollute agroecosystems, put the integrity
      of the environment at risk and become a major route of exposure to humans. The
      present study was carried out in Taxco, Guerrero, Mexico, where millions of tons
      of mine tailings have been deposited. Soils from this region are used for
      agricultural activities. Maize (Zea mays) was selected as a test plant, because
      it is one of the most common and important cereal crops in Mexico and worldwide.
      Thirteen metals were selected and their bioaccumulation in roots, leaves and
      fruits were measured in plants cultivated in soils contaminated with mine
      tailings and those cultivated in non-contaminated soils. The effect of metal
      bioaccumulation on: macro and micromorphology, size, biomass, coloration leaf
      patterns and on DNA damage levels in different structures were determined. The
      bioaccumulation pattern was: root > leaf > fruit, being only Mn and Cr
      bioaccumulated in all three structures and V in the roots and leaves. A
      significant effect of metal bioaccumulation on 50% of the size and leaf shape and
      55% of the biomass characters in Z. mays exposed plants was detected. Regarding
      micromorphological characters, a significant effect of metal bioaccumulation on
      67% of the leaf characters and on 100% of the color basal leaf characters was
      noted. The effect of metal bioaccumulation on the induction of DNA damage (leaf >
      fruit > root) was detected employing single cell gel electrophoresis analysis. An
      approach, in which multi endpoints are used is necessary to estimate the extent
      of the detrimental effects of metal pollution on agroecosystem integrity
      contaminated with mine tailings.

PMID- 30120660
TI  - Genotoxic, biochemical and bioconcentration effects of manganese on Oreochromis
      niloticus (Cichlidae).
AB  - Manganese and iron were found at high concentrations (3.61 mg/L and 19.8 mg/L,
      respectively) in the water of the Rio Doce after the dams of Fundao and Santarem
      broke in Mariana/MG (Brazil). These same metals were found in fish and crustacean
      muscle (15 mg/kg and 8 mg/kg wet weight, respectively) in the specimens collected
      near the Rio Doce's outfall. Due to the variation in Mn concentration found in
      the lower Rio Doce, this study aimed to determine the effects of Mn in
      Oreochromis niloticus, at the concentrations allowed by CONAMA, and in
      concentrations found in the Rio Doce after the dams broke. The animals were
      exposed to the following dissolved concentrations: control group (0.0 mg/L), 0.2;
      1.5 and 2.9 mg/L manganese for 96 h. In addition, a positive control was
      conducted, injecting intraperitoneally with cyclophosphamide (at 25 mg/kg). These
      exposures caused significant erythrocyte micronucleus formation in the organisms
      exposed to the highest concentration, as well a significant increase in the DNA
      damage index of erythrocytes from organisms exposed to 1.5 mg/L and 2.9 mg/L
      treatments. The glutathione S-transferase enzyme activity also showed a
      significant increase in the liver of the organisms exposed to 2.9 mg/L. However,
      catalase activity increased significantly in the gills of the animals exposed to
      all concentrations of manganese that were tested. Manganese bioconcentrated in
      greater quantities in the liver than the gills. Thus, manganese causes
      significant damage to genetic material, generates nuclear abnormalities,
      activates the body's detoxification system and can accumulate in animal tissue.

PMID- 30120661
TI  - Bevacizumab, irinotecan, temozolomide, tyrosine kinase inhibition, and MEK
      inhibition are effective against pleomorphic xanthoastrocytoma regardless of
      V600E status.
AB  - INTRODUCTION: Pleomorphic xanthoastrocytoma (PXA) is a rare Grade II and III
      glioma. Surgical resection is the mainstay of treatment, however, adjuvant
      therapy is sometimes necessary. Given the rarity of PXA, chemotherapeutic
      efficacy data is limited. The importance of the BRAF V600E mutation in the
      context of MAP kinase pathway inhibition is unknown. The purpose of this study
      was to perform an in vivo screen of a variety to agents to determine efficacy
      against both V600E mutant and non-mutant PXA. METHODS: The efficacy of
      bevacizumab, temozolomide, lomustine (CCNU), irinotecan (CPT 11), a tyrosine
      kinase inhibitor (sorafenib), a selective MEK1/2 inhibitor (cobimetinib), and a
      BRAF inhibitor (vemurafenib) were assessed in two subcutaneous xenografts: D645
      PXA (V600E-mutant) and D2363 PXA (V600E-non-mutant) (n = 5-10 mice). Select
      agents were also assessed in an intracranial model of D2363 PXA (n = 6-9).
      Subcutaneous tumor growth and survival were the endpoints. RESULTS: Temozolomide,
      bevacizumab, CPT 11, and sorafenib significantly inhibited subcutaneous tumor
      growth in both V600E-mutant and V600E-non-mutant models (P < 0.05). MEK
      inhibition (cobimetinib) but not BRAF inhibition (vemurafenib) also inhibited
      tumor growth regardless of V600E mutation (P < 0.05). Temozolomide, CPT 11, and
      bevacizumab also prolonged survival in a V600E-non-mutant intracranial model
      (median overall survival (OS) 68.5, 62.5, and 42.5 days, respectively) in
      contrast to controls (31.5 days, P < 0.001). CONCLUSIONS: These findings suggest
      that when adjuvant treatment is clinically indicated for PXA, temozolomide, CPT
      11, or bevacizumab may be considered. Additionally, a trial of a MEK inhibitor or
      tyrosine kinase inhibitor could be considered for PXA regardless of V600E
      mutation status.

PMID- 30120662
TI  - Platelet count is associated with outcome in cancer patients with stroke.
AB  - INTRODUCTION: Cerebrovascular disease (CVD) and cancer are among the most common
      causes of mortality worldwide, preceded only by ischemic heart disease (IHD).
      Thrombocytopenia was shown to be associated with poor outcomes in IHD and CVD in
      the general population. This study aimed to assess the relationship of
      thrombocytopenia with poor outcomes in cancer patients with CVD. MATERIALS AND
      METHODS: Data on patients with concomitant CVD and cancer who were initially
      treated at a cancer referral center between January 2010 and December 2017 were
      included. Thrombocytopenia was defined as a platelet count < 150,000/mm3 during
      the first 24 h of CVD symptom onset. The IRB (CI/837/17) approved the review of
      clinical records. RESULTS: Among 268 cancer patients with CVD included in the
      study, 210 met the inclusion criteria. Median overall survival of the entire
      cohort was 7.2 months, which was significantly shorter in males (p = 0.029) and
      patients with hematologic tumors (p = 0.009), hemorrhagic CVD (p < 0.001),
      altered mental status (p < 0.001), and thrombocytopenia (p < 0.001). Multiple
      regression logistic analysis revealed that thrombocytopenia (risk ratio [RR] 1.6,
      95% confidence interval [CI] 1.1-2.4) and altered mental status (RR 2.7, 95% CI
      1.9-4.0) remained statistically significant risk factors for mortality.
      CONCLUSION: In cancer patients with CVD, thrombocytopenia at the time of CVD
      diagnosis and altered mental status during initial clinical evaluation were
      associated with higher mortality, which should be confirmed in future studies.

PMID- 30120663
TI  - Influence of Apoptotic Bodies and Apoptotic Microvesicles on NO Production in
      Macrophages.
AB  - We studied the effect of extracellular vesicular particles generated during
      apoptosis by macrophages of M0, M1 and M2 phenotypes on spontaneous and LPS
      stimulated production of NO. The fractions of apoptotic bodies and apoptotic
      microvesicles were obtained in the primary cultures of peritoneal macrophages
      undergoing apoptosis. The effect of these microparticles on LPS-induced
      proinflammatory response of recipient macrophages critically depends on the
      initial phenotype of "donor" macrophages. Microvesicles and especially apoptotic
      bodies from M1 macrophages stimulate basal NO production. LPS stimulation of
      these macrophages preincubated with apoptotic bodies was not followed by further
      growth of NO production; in macrophages preincubated with microvesicles, LPS even
      suppressed NO production. Apoptotic microparticles obtained from M2 macrophages
      produced little effect on the basal production of NO. LPS stimulation of
      macrophages-recipients preincubated with microparticles from M2 macrophages did
      not enhance NO production. Incubation of macrophages with apoptotic
      microparticles induces the formation of endotoxic tolerance.

PMID- 30120666
TI  - Return to Work of Cancer Survivors: Predicting Healthcare Professionals' Assumed
      Role Responsibility.
AB  - Purpose Returning to work is highly beneficial for many cancer survivors. While
      research has documented the significance of healthcare professionals in the
      process of return to work (RTW), very little is known about those professionals'
      views regarding their responsibility for RTW. The purpose of the present study
      was to identify factors that predict the extent to which healthcare professionals
      view involvement in the RTW of cancer survivors as part of their role. Methods In
      a cross-sectional design, questionnaires measuring attitudes regarding personal
      role responsibility for RTW, team role responsibility for RTW and benefits of RTW
      were administered to 157 healthcare professionals who care for working-age cancer
      survivors: oncologists, occupational physicians, family physicians, oncology
      nurses, oncology social workers, and psychologists. Results Both belief in the
      benefits of RTW, and the view that RTW is the team responsibility of healthcare
      professionals working with cancer survivors, are positively related to viewing
      RTW as part of the responsibilities of one's personal professional role.
      Moderation analysis indicated that perception of team responsibility for RTW
      moderates the effect of the perceived benefits of RTW, such that the perception
      of benefits is significantly associated with personal role responsibility only
      when there is a low level of perceived team responsibility. Conclusions Issues
      related to RTW should be routinely included in basic and advanced training of
      healthcare professionals involved in the treatment of working-age cancer
      survivors, to increase awareness of this aspect of cancer survivors' well-being
      and position RTW as part of healthcare professionals' role responsibilities.

PMID- 30120665
TI  - Combined Effect of NF-kappaB Inhibitor and beta2-Adrenoreceptor Agonist on Mouse
      Mortality and Blood Concentration of Proinflammatory Cytokines in Sepsis.
AB  - Experiments on random-bred albino mice showed that NF-kappaB inhibitor (BAY 11
      7082) and beta2-adrenoreceptor agonist (dexmedetomidine hydrochloride)
      significantly reduced mouse mortality in 4 and 24 h after sepsis modeling
      (intraperitoneal administration of E. coli) by reducing blood levels of
      proinflammatory cytokines TNFalpha, IL-1beta, and IL-6. The combined
      administration of NF-kappaB inhibitor and beta2-adrenoreceptors agonist have an
      additive effect.

PMID- 30120664
TI  - Collagen Hydrolysis Products Reduce the Formation of Stress-Induced Ulcers by
      Regulating Stress-Associated Activation of the Neuroendocrine and Immune Systems.
AB  - We studied the effect of collagen fragments (PGP and AcPGP) on serum content of
      epinephrine, corticosterone, and IL-1beta in rats subjected to water-immersion
      stress. The degree of local inflammation accompanying ulceration was assessed by
      IL-1beta production by ln. gastricus caudalis cells. In 1 h, the sharp increase
      in hormone concentrations in the blood of stressed animals reflected the high
      stress intensity. Intranasal administration of PGP reduced the area of stress
      induced ulcers by 63%, prevented the increase in the levels of stress hormones
      and the main proinflammatory cytokine in rat blood. The concentrations of IL
      1beta in cell culture from regional lymph node of experimental animals returned
      to normal in 24 and 48 h after the stress. Acetylation of PGP prevents with
      gastroprotection, but does not abrogate other properties of the peptide.

PMID- 30120667
TI  - Laparoscopic Cholecystectomy for Gallbladder Duplication.

PMID- 30120668
TI  - Visceral Obesity and Open Passive Drainage Increase the Risk of Pancreatic
      Fistula Following Distal Pancreatectomy.
AB  - BACKGROUND: The predictive risk factors of clinically relevant pancreatic fistula
      (CR-PF) following distal pancreatectomy (DP) remain to be identified. METHODS:
      This is a retrospective cohort analysis of a single-institution database of
      patients undergoing DP, taking into account usual demographic, operative, and
      pathologic variables and visceral fat area (VFA), total muscle area (TMA), and
      surface muscle index (SMI) measured on preoperative CT scan. The primary end
      point was CR-PF. All variables associated with a p value < 0.05 on univariate
      analysis were included in a logistic regression model for multivariate analysis.
      RESULTS: From 2012 to 2016, 208 patients operated by 4 pancreatic surgeons
      underwent DP including 32 (15%) who developed CR-PF. Risk factors of CR-PF on
      univariate analysis were: BMI >= 25 kg/m2 (p = 0.050), VFA >= 92 cm2 (p = 0.006),
      laparotomy (p = 0.023), main pancreatic duct dilatation (p = 0.035), open passive
      drainage (versus closed suction drainage) (p = 0.001), and blood loss >= 225 ml
      (p = 0.001). Sarcopenia did not influence the risk of CR-PF (p = 0.076). On
      multivariate analysis, VFA >= 92 cm2 (OR 3.14; IC 95% (1.18-8.31), p = 0.022),
      blood loss >= 225 ml (OR: 2.72; IC 95% (1.06-6.96), p = 0.037), and open passive
      drainage (OR 3.72; IC 95% (1.40-9.87) p = 0.008) were three independent
      predictive factors of CR-PF. A CR-PF risk score was developed, predicting a 0%
      risk of CR-PF when no risk factors were present and a 39% risk when the 3 risk
      factors were present. CONCLUSIONS: Visceral obesity, blood loss >= 225 ml and
      open passive drainage significantly increase the risk of CR-PF following DP.

PMID- 30120669
TI  - Use of qPCR-Based Cercariometry to Assess Swimmer's Itch in Recreational Lakes.
AB  - Swimmer's itch (cercarial dermatitis) is a nuisance encountered by bathers and
      recreational water users worldwide. The condition is caused by the penetration of
      larval digenean trematodes (cercariae) of the family Schistosomatidae, into the
      skin, following their release into freshwater from pulmonate snails that serve as
      the intermediate hosts for these parasites. This study utilizes qPCR-based
      cercariometry to monitor and quantify cercariae from water samples collected at 5
      lakes in northern Michigan. The resolution provided by qPCR facilitated
      assessment of the environmental and biological drivers of swimmer's itch-causing
      cercariae concentrations, allowing us to demonstrate that cercarial abundance is
      greatest at the top of the water column, in locations with prevailing on- and
      alongshore winds.

PMID- 30120670
TI  - De-urbanization and Zoonotic Disease Risk.

PMID- 30120671
TI  - The Banality of Anal: Safer Sexual Erotics in the Gay Men's Health Crisis' Safer
      Sex Comix and Ex Aequo's Alex et la vie d'apres.
AB  - Analyzing two harm reduction comics campaigns-one early in the AIDS crisis (the
      Gay Men's Health Crisis' [GMHC] 1980s Safer Sex Comix) and one more recent
      (Fabrice Neaud and Thierry Robberecht's 2008 Alex et la vie d'apres), I explore
      tensions between queer safer sexual erotics and national discourses of sexual
      norms/deviation raised by Cindy Patton and William Haver at the height of AIDS
      discourse theory in 1996, approximately halfway between the comics. Using these
      theorists' reflections on the history of AIDS activism/representation as a hinge,
      I explore the manifestation/transformation a decade later of the ethical,
      educational, and erotic issues they raise. Both foreground the ways that HIV,
      safer sex, and/or eroticism pose difficulties for systems of linguistic and
      visual representation. Combining text and image, comics-a common harm reduction
      medium-epitomize this representational issue. While the GMHC addresses an
      immediate need for information about safer sex, Alex attempts to tackle the
      unrepresentability/unthinkability of safer and/or seropositive sex(uality). Safer
      Sex Comix, while largely prioritizing directness above formal experimentation,
      employ strategies of transgressing the borders of the comics panel to emphasize a
      plethora of lower-risk sexual acts. The most visually inventive moments in Alex
      represent Alex's feelings of unintelligbility post-diagnosis, but the comic
      restricts its representation of sex only to anal intercourse, and it proves
      unable to visualize alternative formulations of the erotic, turning to more
      normative narratives and images as earlier, visually explicit unsafe sexual
      encounters are replaced with more a/illusive representations post-conversion,
      literalizing the unrepresentability of seropositive erotic life.

PMID- 30120673
TI  - Post-cardiotomy venovenous extracorporeal membrane oxygenation without
      heparinization.
AB  - We present the cases of eight patients (mean age 75 years; EuroSCORE II 17.0 +/-
      22.0) who underwent post-cardiotomy venovenous extracorporeal membrane
      oxygenation (ECMO) without heparinization due to serious bleeding. Three liver
      cirrhosis, two chronic hemodialysis, three redo sternotomy, and two urgent
      surgery cases were included. Respiratory ECMO Survival Prediction score was - 5.1
      +/- 4.2 (estimated survival rate: approximately 30%). Mean ECMO duration was 14
      days with 9 circuit exchanges. Five patients were weaned from ECMO and three were
      discharged alive at 90 days (survival 37.5%). There was a case of pump-head
      thrombosis requiring urgent circuit exchange. All experienced bleeding
      complications without clinically apparent pulmonary thromboembolism. Disseminated
      Intravascular Coagulation scores (Pre 1.3 +/- 0.8 vs. Post 3.8 +/- 1.7; p < 0.05)
      significantly increased (N = 6). Post-cardiotomy ECMO without heparinization
      facilitated patient rescue at a reasonable survival rate. However, bleeding
      complications were still observed. More sophisticated management protocols are
      warranted.

PMID- 30120674
TI  - Spontaneous ascending aortic rupture in a pregnant woman with neurofibromatosis
      type 1.
AB  - Neurofibromatosis type 1 (NF-1) is an autosomal dominant disorder that affects 1
      in 3000 individuals. Vascular involvement in NF-1 is a well-recognized, but rare,
      feature of this disease. In pregnant women, the risk of aortic dissection or
      rupture is elevated during pregnancy and the postpartum period. We report a
      pregnant woman who had a history of NF-1 with a spontaneous ascending aortic
      rupture. This rupture was successfully treated by emergent surgery. The mother
      and the 28-week-gestation newborn recovered uneventfully. During 7 years of
      follow-up, aorta of the patient shows no significant change. A review of the
      literature regarding the pathogenesis of this condition is also presented.

PMID- 30120672
TI  - Mitochondrial alterations accompanied by oxidative stress conditions in skin
      fibroblasts of Huntington's disease patients.
AB  - Huntington disease (HD) is an autosomal dominant neurodegenerative disorder
      manifesting as progressive impairment of motor function and different
      neuropsychiatric symptoms caused by an expansion of CAG repeats in huntingtin
      gene (HTT). Mitochondrial dysfunction and bioenergetic defects can contribute to
      the course of the disease, however, the molecular mechanism underlying this
      process is still largely unknown. In this study, we aimed to determine several
      mitochondrial parameters in HD fibroblasts and assess their relevance to the
      disease progression as well as to value mitochondrial pathology in peripheral
      cells as disease potential biomarker. We showed that HD fibroblasts demonstrate
      significantly lower growth rate compared to control fibroblasts despite the lack
      of cell cycle perturbations. In order to investigate mitochondrial contribution
      to cell growth differences between HD and healthy cells, we provided insight into
      various mitochondrial parameters. Conducted experiments have revealed a
      significant reduction of the ATP level in HD fibroblasts accompanied by a
      decrease in mitochondrial metabolic activity in relation to the cells from
      healthy donors. Importantly, there were no differences in the mitochondrial
      membrane potential (mtDeltaPsi) and OXPHOS complexes' levels. Slightly increased
      level of mitochondrial superoxide (mt. O2*-), but not cytosolic reactive oxygen
      species (cyt. ROS), has been demonstrated. We have also observed significantly
      elevated levels of some antioxidant enzymes (SOD2 and GR) which may serve as an
      indicator of antioxidant defense system in HD patients. Thus, we suggest that
      mitochondrial alterations in skin fibroblasts of Huntington's disease patients
      might be helpful in searching for novel disease biomarkers.

PMID- 30120675
TI  - Arab Men and Women's Conceptualization of Mental Health and Depression: A
      Qualitative Study from the Middle East.
AB  - Cardiovascular diseases are the leading cause of death worldwide. Among
      cardiovascular patients, depression is associated with an increased morbidity and
      mortality. Understanding how depression is conceptualized from cardiovascular
      patients' perspective can help with prevention, early detection, and treatment
      for depression. This might reduce cardiovascular morbidity and mortality, and
      save health care costs. To the best of our knowledge, there is no study in the
      Gulf region exploring depression among Arab cardiovascular patients. The purpose
      of this exploratory ethnographic qualitative research is to investigate how Arab
      male and female patients with cardiovascular disease conceptualize mental health
      and depression. Two theoretical frameworks guided this research: (1) The
      Ecological Perspective, and (2) Kleinman's Explanatory Model of Health and
      Illness. Using maximum variation purposive sampling, thirty (30) male and twenty
      five (25) female, self-identified, Arab cardiovascular patients were recruited as
      research participants. Individual in-depth interviews were conducted using a semi
      structured questionnaire. Thematic analysis was performed to generate themes.
      Nvivo 10, a qualitative data analysis software, was used to organize the
      narrative data. The participants in this study placed great emphasis on the
      manifestations of mental illness and their impact on both themselves and their
      families. Four major themes were identified from their narratives: psychological
      and physical disturbances; unfavorable personal characteristics; work issues and
      financial constraints; lack of family and social support. The knowledge generated
      in this study might help increase awareness, prevention of and treatment for
      depression among cardiovascular patients in Qatar. The findings from this study
      can also be used to inform a multi-disciplinary and multi-sectoral intervention
      approach that is contextualized to meet the mental health care needs of Arab
      cardiovascular patients, thus reducing cardiovascular diseases morbidity and
      mortality in Qatar and the Gulf region.

PMID- 30120677
TI  - Multiple Non-Essential Transition Metals Are Accumulated in Carotid
      Atherosclerotic Plaques: Missing Link in Atherosclerosis?
AB  - Population studies revealed that metal exposure through food, environment, and
      smoking was related with increased risk of cardiovascular disease. In this study,
      we determined complex chemical elements in surgical carotid endarterectomy
      specimens and carotid tissues from autopsies without atherosclerosis.
      Atherosclerotic plaques from 41 endarterectomies and normal carotid tissue from
      30 autopsies were collected and elemental composition was determined by
      inductively coupled plasma optical emission spectrometry (ICP-OES) method. Eleven
      (26.8%) patients never smoked in carotid endarterectomy group. One patient was
      brass souvenir worker and one was goldsmith and others did not have direct
      contact with metals in the carotid endarterectomy group. Na, Cu, Mn, Bi, Co, Mo,
      Ni, Pb, Sb, Se, Sn, Ti, and W levels were not different between two groups. Bi,
      Co, Mo, Pb, Ti, and W were below the detection limit of ICP-OES in both groups.
      Concentrations of Mg, K, Ca, P, Fe, B, Zn, Al, As, Cr, Pt, and Hg were
      significantly higher in carotid endarterectomies than normal carotid tissue
      samples. Cd and S values were significantly higher in autopsy samples. There is
      significant multiple non-essential transition metal accumulation in
      atherosclerotic carotid endarterectomy plaques. The cardiovascular consequences
      of metal toxicity have not been researched adequately due to large emphasis on
      the role of cholesterol in atherosclerosis. High level of non-essential
      transition metal elements in the carotid atherosclerotic plaques may add the
      missing link of atherogenesis and may necessitate new treatment and prevention
      strategies in carotid disease if confirmed by further research.

PMID- 30120676
TI  - Easy In Vitro Synthesis of Optimised Functioning Reporter mRNA from Common eGFP
      Plasmid.
AB  - The extensive growth in number and importance of experiments and clinical-aimed
      techniques based solely or majorly on the activity of RNA strands, e.g.
      CRSPR/Cas9 and siRNA, has put emphasis on the necessity of standardisation of
      experiments with RNA. Considering RNA degradation during its handling seems to be
      a major hindrance in all RNA-based tools, the assessment of its integrity is of
      utmost importance. Furthermore, evaluating whether the RNA to be transfected is
      intact requires time-consuming electrophoresis protocol. In view of the RNA
      lability and the necessity for controlling experiments performed with this
      molecule, the transfection of a reporter mRNA may be of aid in optimising
      experiments. Nevertheless, commercial reporter mRNAs are far less available than
      plasmids for such purpose. Thus, in this work, we aimed at the optimisation of an
      easily performed protocol to produce a suitable eGFP mRNA. By utilising molecular
      biology kits customarily employed in molecular biology laboratories working with
      RNA-based techniques and starting from any eGFP coding vector, we produced four
      mRNA molecules: (1) eGFP mRNA (non-polyadenylated); (2) Kozak-eGFP mRNA (non
      polyadenylated, produced from the Kozak-containing amplicon); (3) eGFP-PolyA mRNA
      (polyadenylated); (4) Kozak-eGFP-PolyA mRNA (containing both signals, Kozak
      sequence and poly(A) tail). These mRNA molecules were transfected into HEK 293 FT
      cells, readily transfectable, and into the MDBK bovine lineage, which has been
      observed as difficult-to-transfect DNA constructs. eGFP expression could be
      detected both by flow cytometry and by fluorescence microscopy after transfection
      with the polyadenylated mRNAs. Upon cytometric analysis, we noted a marked
      difference among the mRNA groups (p < 0.01), both in fluorescent population
      percentage and in florescence intensity. We showed here the necessity of the
      polyadenylation step in order to achieve cell expression of the eGFP observable
      under fluorescence microscopy. The presence of the Kozak sequence, as a 5'
      element, seems to augment significantly the level of protein produced upon mRNA
      transfection. We presented here an easy protocol to allow production of
      functioning mRNAs from any DNA construct. The molecules produced may aid in the
      standardisation and controlling most of the RNA-related experiments as well as it
      gives proper guidance for researchers performing expression of other proteins
      through mRNA transfection.

PMID- 30120678
TI  - Docetaxel-rechallenge in castration-resistant prostate cancer: defining clinical
      factors for successful treatment response and improvement in overall survival.
AB  - PURPOSE: The purpose of the study was to define clinical factors for successful
      treatment response and re-exposure to docetaxel in metastatic castration
      resistant prostate cancer (mCRPC). METHODS: An mCRPC database of patients
      receiving first-line docetaxel and rechallenge courses was established. Several
      clinical factors were evaluated for prediction of treatment response.
      Multivariate cox-regression analysis was used to define pre-treatment and
      treatment factors for survival. RESULTS: Between 2005 and 2013, 94 patients with
      mCRPC were treated with docetaxel. Full data set and follow-up were available for
      62 patients. Median follow-up was 84 m [interquartile range (IQR) 64-104 m].
      Median biochemical progression-free survival (bPFS) and overall survival under
      docetaxel were 9 m (IQR 5-16 m) and 20 m (IQR 16-26 m), respectively. Partial PSA
      response at first docetaxel-sequence (n = 62), rechallenge (n = 32), and third
      sequence (n = 22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from
      start of primary androgen deprivation to CRPC > 47 m was the only independent pre
      treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p =
      0.015). Interestingly, there was a strong trend for improved overall survival in
      patients with high Gleason Score (Hazard Ratio 0.58; p = 0.08). Partial PSA
      response at docetaxel-rechallenge (Hazard Ratio 0.31; p = 0.008) and treatment
      free interval > 3 m (Hazard Ratio 3.49; p = 0.014) were the only independent
      predictive factors under taxane treatment for overall survival. CONCLUSION:
      Despite novel hormonal drugs, docetaxel still plays an important role in the
      treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a
      treatment-free interval > 3 m benefit most from docetaxel re-exposure.

PMID- 30120679
TI  - Transplant nephrectomy after graft failure: is it so risky? Impact on morbidity,
      mortality and alloimmunization.
AB  - PURPOSE: To determine the impact of transplant nephrectomy on morbidity and
      mortality and HLA immunization. METHODS: All patients who underwent transplant
      nephrectomy in our centre between 2000 and 2016 were included in this study. A
      total of 2822 renal transplantations and 180 transplant nephrectomies were
      performed during this period. RESULTS: The indications for transplant nephrectomy
      were graft intolerance syndrome: 47.2%, sepsis: 22.2%, vascular thrombosis:
      15.5%, tumour: 8.3% and other 6.8%. Transplant nephrectomies were performed via
      an intracapsular approach in 61.7% of cases. The blood transfusion rate was 50%,
      the morbidity rate was 38% and the mortality rate was 3%. Transplant
      nephrectomies more than 12 months after renal transplant failure were associated
      with more complications (p = 0.006). Transfusions in the context of transplant
      nephrectomy had no significant impact on alloimmunization. CONCLUSION: The risk
      of bleeding, and therefore of transfusion, constitutes the major challenge of
      this surgery in patients eligible for retransplantation. Even if transfusions in
      this context of transplant nephrectomy had no significant impact on
      alloimmunization, this high-risk surgery, whenever possible, must be performed
      electively in a well-prepared patient.

PMID- 30120681
TI  - Social Determinants of Health and Human Papillomavirus Vaccination Among Young
      Adults, National Health Interview Survey 2016.
AB  - Human papillomavirus (HPV) vaccination has the potential to reduce the burden of
      anogenital cancers. Vaccine uptake remains suboptimal, especially among young
      adults. Social determinants of health (SDOH) are societal level conditions that
      may indirectly influence health behaviors, including HPV vaccination. The purpose
      of this study was to assess HPV vaccination and SDOH among young adult women and
      men. The 2016 National Health Interview Survey was restricted to participants
      ages 18-26 (n = 3593). The Healthy People 2020 SDOH Framework was used to
      identify variables for economic stability, health and healthcare, education,
      social and community context, and neighborhood and built environment. Survey
      weighted logistic regression models identified SDOH variables significantly
      associated with HPV vaccination. Reported HPV vaccination occurred for 45.7% of
      women and 14.5% of men in the sample. Among women, education determinants-highest
      level of education completed and English language-were significantly associated
      with HPV vaccination. Men (adjusted OR 0.65, 95% CI 0.54, 0.79) and women
      (adjusted OR 0.66, 95% CI 0.49, 0.90) who did not use the Internet to look up
      health information were at lower odds to be vaccinated for HPV. These findings
      can inform future HPV vaccine uptake efforts by focusing specifically on these
      SDOH areas-education and health and healthcare. Identifying SDOH leverage points
      is critical to promoting HPV vaccination and ultimately reducing HPV-associated
      cancers.

PMID- 30120680
TI  - Comparison of two detection systems for circulating tumor cells among patients
      with renal cell carcinoma.
AB  - BACKGROUND/AIMS: Detection of circulating tumor cells (CTCs) in cancer patients
      has diagnostic and prognostic importance. However, the clinical implications of
      CTC detection in patients with renal cell carcinoma (RCC) are still unclear. In
      this study, we investigated the clinical significance of CTCs using two detection
      systems, the CellSearch system (CSS) and isolation by size of epithelial tumor
      cells (ISET), among RCC patients. METHODS: We recruited 36 RCC patients and 22
      healthy volunteers as controls. Blood was drawn before treatment. Samples were
      analyzed using the CSS and ISET. We prospectively followed the RCC patients to
      determine overall and progression-free survival. RESULTS: We did not detect CTCs
      in the control group using either the CSS or ISET. CTCs were detected in 7/36
      patients (19.4%) using the CSS and in 13/36 patients (36.1%) using ISET, while
      circulating microemboli (CTMs) were detected in three patients (8.3%). The
      presence of ISET-detected CTCs correlated with clinical tumor node metastasis
      (TNM) stages, while the CSS-detected CTCs did not. After 36 months (median), CTCs
      detected by both methods failed to correlate with overall and progression-free
      survival among RCC patients. CONCLUSION: We discovered that ISET is more suitable
      than the CSS for detecting CTCs in RCC patients. The presence of CTCs/CTMs in RCC
      patients correlated with higher TNM stages, suggesting that the presence of CTCs
      could be a prognostic marker in RCC patients.

PMID- 30120682
TI  - The Differential Time-Varying Effect Model (DTVEM): A tool for diagnosing and
      modeling time lags in intensive longitudinal data.
AB  - With the recent growth in intensive longitudinal designs and the corresponding
      demand for methods to analyze such data, there has never been a more pressing
      need for user-friendly analytic tools that can identify and estimate optimal time
      lags in intensive longitudinal data. The available standard exploratory methods
      to identify optimal time lags within univariate and multivariate multiple-subject
      time series are greatly underpowered at the group (i.e., population) level. We
      describe a hybrid exploratory-confirmatory tool, referred to herein as the
      Differential Time-Varying Effect Model (DTVEM), which features a convenient user
      accessible function to identify optimal time lags and estimate these lags within
      a state-space framework. Data from an empirical ecological momentary assessment
      study are then used to demonstrate the utility of the proposed tool in
      identifying the optimal time lag for studying the linkages between nervousness
      and heart rate in a group of undergraduate students. Using a simulation study, we
      illustrate the effectiveness of DTVEM in identifying optimal lag structures in
      multiple-subject time-series data with missingness, as well as its strengths and
      limitations as a hybrid exploratory-confirmatory approach, relative to other
      existing approaches.

PMID- 30120683
TI  - Group communication analysis: A computational linguistics approach for detecting
      sociocognitive roles in multiparty interactions.
AB  - Roles are one of the most important concepts in understanding human
      sociocognitive behavior. During group interactions, members take on different
      roles within the discussion. Roles have distinct patterns of behavioral
      engagement (i.e., active or passive, leading or following), contribution
      characteristics (i.e., providing new information or echoing given material), and
      social orientation (i.e., individual or group). Different combinations of roles
      can produce characteristically different group outcomes, and thus can be either
      less or more productive with regard to collective goals. In online collaborative
      learning environments, this can lead to better or worse learning outcomes for the
      individual participants. In this study, we propose and validate a novel approach
      for detecting emergent roles from participants' contributions and patterns of
      interaction. Specifically, we developed a group communication analysis (GCA) by
      combining automated computational linguistic techniques with analyses of the
      sequential interactions of online group communication. GCA was applied to three
      large collaborative interaction datasets (participant N = 2,429, group N =
      3,598). Cluster analyses and linear mixed-effects modeling were used to assess
      the validity of the GCA approach and the influence of learner roles on student
      and group performance. The results indicated that participants' patterns of
      linguistic coordination and cohesion are representative of the roles that
      individuals play in collaborative discussions. More broadly, GCA provides a
      framework for researchers to explore the micro intra- and interpersonal patterns
      associated with participants' roles and the sociocognitive processes related to
      successful collaboration.

PMID- 30120684
TI  - Influenza-associated encephalopathy with extensive reversible restricted
      diffusion within the white matter.

PMID- 30120686
TI  - Distal 1q21.1 and proximal 1q21.2 microduplication in a child with attention
      deficit hyperactivity disorder.

PMID- 30120685
TI  - Evaluation of optic nerve head changes with optic coherence tomography in
      patients with idiopathic intracranial hypertension.
AB  - In the case of mild papilledema, fundoscopy findings may sometimes be
      insufficient, leading to false and misleading indices in the diagnosis of early
      stage idiopathic intracranial hypertension (IIH). This study aims to evaluate
      these patients through optic coherence tomography (OCT). The study included 54
      individuals diagnosed with IIH and 48 healthy individuals in the control group.
      All patients underwent neurological and ophthalmologic examinations. Opening
      pressure values of patients' cerebrospinal fluid (CSF) were recorded. We measured
      the thickness of the retinal nerve fiber layer (RNFL) and the ganglion cell
      complex, cup volume, and the optical disc area, as well as the neuroretinal rim
      in both groups. A total of 108 eyes from the patient group and 96 eyes from the
      control group were evaluated. It was found that the mean value of the RNFL
      thickness of the IIH patients was greater than the control group in the following
      eight segments: superior nasal, superior temporal, inferior nasal, inferior
      temporal, nasal superior, nasal inferior, temporal superior, and temporal
      inferior (p < 0.01 for all). In contrast to the control group, the disc and rim
      area values of the patient group were higher (p < 0.01), while the cup volume was
      smaller (p < 0.01) than in the control group. In the patient group, a positive
      correlation was observed between the papilledema grade and the RNFL thickness (r
      = 0.64, p < 0.01), CSF opening pressure (r = 0.59, p < 0.01), disc area (r =
      0.68, p < 0.01), and rim area (r = 0.70, p < 0.01). Furthermore, RNFL thickness,
      CSF opening pressure (r = 0.61, p < 0.01), disc area (r = 0.71, p < 0.01), and
      rim area (r = 0.71, p < 0.01) values were determined to be positively correlated
      to each other. OCT is believed to contribute to the diagnosis of IIH, by
      providing reliable data on optical cup volume, optical disc and rim area, and a
      greater RNFL thickness.

PMID- 30120687
TI  - PLA2G6-related parkinsonism presenting as adolescent behavior.

PMID- 30120688
TI  - Evolutionary Suicide of Prey: Matsuda and Abrams' Model Revisited.
AB  - Under the threat of predation, a species of prey can evolve to its own
      extinction. Matsuda and Abrams (Theor Popul Biol 45:76-91, 1994a) found the
      earliest example of evolutionary suicide by demonstrating that the foraging
      effort of prey can evolve until its population dynamics cross a fold bifurcation,
      whereupon the prey crashes to extinction. We extend this model in three
      directions. First, we use critical function analysis to show that extinction
      cannot happen via increasing foraging effort. Second, we extend the model to non
      equilibrium systems and demonstrate evolutionary suicide at a fold bifurcation of
      limit cycles. Third, we relax a crucial assumption of the original model. To find
      evolutionary suicide, Matsuda and Abrams assumed a generalist predator, whose
      population size is fixed independently of the focal prey. We embed the original
      model into a three-species community of the focal prey, the predator and an
      alternative prey that can support the predator also alone, and investigate the
      effect of increasingly strong coupling between the focal prey and the predator's
      population dynamics. Our three-species model exhibits (1) evolutionary suicide
      via a subcritical Hopf bifurcation and (2) indirect evolutionary suicide, where
      the evolution of the focal prey first makes the community open to the invasion of
      the alternative prey, which in turn makes evolutionary suicide of the focal prey
      possible. These new phenomena highlight the importance of studying evolution in a
      broader community context.

PMID- 30120689
TI  - Amanah and Muslim Identity: Relationships with Religious and Psychological
      Adjustment in Malaysia.
AB  - Amanah refers to the accountability of Muslims to their community. In Malaysian
      Muslim university students (N = 209), an Amanah Scale predicted a stronger sense
      of identity along with more adaptive religious and psychosocial functioning.
      Multiple regression analyses identified Accountability to Society as especially
      influential, but Accountability to Allah exhibited at least some problematic
      implications. Amanah mediated Identity linkages with some measures of religious
      and psychological adjustment, but also suppressed Identity relationships with
      greater self-knowledge and lower anxiety. These data confirmed the importance of
      communal commitments in Muslim mental health, suggested that accountability may
      have limited liabilities as well as more obvious psychosocial advantages, and
      identified possible complexities in the assessment of Accountability to Allah.

PMID- 30120690
TI  - Religious Involvement, Anxiety/Depression, and PTSD Symptoms in US Veterans and
      Active Duty Military.
AB  - Religious involvement is associated with mental health and well-being in non
      military populations. This study examines the relationship between religiosity
      and PTSD symptoms, and the mediating effects of anxiety and depression in
      Veterans and Active Duty Military (V/ADM). This was a cross-sectional multi-site
      study involving 585 V/ADM recruited from across the USA. Inclusion criteria were
      having served in a combat theater and PTSD symptoms. Demographics, military
      characteristics, and social factors were assessed, along with measurement of
      religiosity, PTSD symptoms, depression, and anxiety. Bivariate and multivariate
      analyses examined the religiosity-PTSD relationship and the mediating effects of
      anxiety/depression on that relationship in the overall sample and stratified by
      race/ethnic group (White, Black, Hispanic). In bivariate analyses, the
      religiosity-PTSD relationship was not significant in the overall sample or in
      Whites. However, the relationship was significant in Blacks (r = - 0.16, p =
      0.01) and in Hispanics (r = 0.30, p = 0.03), but in opposite directions. In the
      overall sample, religiosity was inversely related to anxiety (r = - 0.07, p =
      0.07) and depression (r = - 0.21, p < 0.0001), especially in Blacks (r = - 0.21,
      p = 0.001, and r = - 0.34, p < 0.0001, respectively); however, in Hispanics,
      religiosity was positively related to anxiety (r = 0.32, p = 0.02) as it was to
      PTSD symptoms. When anxiety/depression was controlled for in multivariate
      analyses, the religiosity-PTSD relationship in the overall sample reversed from
      negative to positive, approaching statistical significance (B = 0.05, SE = 0.03,
      p = 0.079). In Blacks, the inverse association between religiosity and PTSD was
      explained by quality of relationships, whereas the positive relationship in
      Hispanics was explained by anxiety symptoms. In conclusion, religiosity was
      inversely related to PTSD symptoms in Blacks, positively related to PTSD in
      Hispanics, and unrelated to PTSD in the overall sample and in Whites.
      Anxiety/depression partially mediated the relationship in the overall sample and
      in Hispanics. Although longitudinal studies will be necessary to determine how
      these relationships come about, consideration should be given to
      spiritual/religious interventions that target anxiety/depression in V/ADM with
      PTSD.

PMID- 30120692
TI  - Guest editorial for the IJCARS special issue on MICCAI 2017.

PMID- 30120693
TI  - Transected nasogastric tube: a rare complication of nasogastric feeding.

PMID- 30120691
TI  - Expression profiles of 14 small heat shock protein (sHSP) transcripts during
      larval diapause and under thermal stress in the spruce budworm, Choristoneura
      fumiferana (L.).
AB  - Diapause is an important strategy for certain insect species to survive
      unfavorable environmental conditions, including low temperatures experienced when
      they overwinter in cold climate. Many studies have indicated that the increased
      expression of heat shock proteins during diapause improves the thermal tolerance
      of insects. However, the relationship between small heat shock proteins (sHSPs)
      and diapause is not clear or well-researched. In this study, we investigated the
      transcript levels of 14 sHSP genes in the spruce budworm, Choristoneura
      fumiferana, a major pest of spruce and fir in Canada, during pre-diapause,
      diapause, and post-diapause under normal rearing conditions and in response to a
      heat shock treatment. We found that sHSP expression profiles could be classified
      into five patterns under normal laboratory conditions: pattern I was upregulated
      only during pre-diapause, pattern II was upregulated only during diapause,
      pattern III was constantly expressed throughout diapause, pattern IV was
      upregulated in both pre-diapause and diapause, and pattern V was upregulated only
      during post-diapause. After heat shock, five different expression patterns were
      observed: pattern I responded weakly or not at all throughout diapause, pattern
      II responded weakly during the diapause stage but strongly at the onset of
      diapause and in the post-diapause period, pattern III was upregulated only during
      post-diapause, pattern IV was strongest during diapause, and pattern V was
      strongest only in early diapause. These complex expression profiles lead us to
      suggest that most of the sHSP genes are involved in the diapause process and that
      they may have multiple and important roles in different phases of this process.

PMID- 30120694
TI  - The Effects of Fillers and Binders on the Accuracy of Tablet Subdivision.
AB  - The effects of excipients on the accuracy of tablet subdivision are severely
      underinvestigated. In this study, placebo tablets were prepared using a combined
      mixture design of fillers and binders to evaluate the effect of these excipients
      on subdivision accuracy. The responses assessed were mass loss, mass variation,
      tablet fragmentation, and increased friability. Dicalcium phosphate dihydrate
      (DCP) gave rise to more uniform and denser tablets than microcrystalline
      cellulose (MCC), thus resulting in greater subdivision accuracy. The binder type,
      hydroxypropylcellulose (HPC) or polyvinylpyrrolidone (PVP), did not affect the
      subdivision of DCP tablets. On the contrary, the structural similarity between
      HPC and MCC led to improved subdivision accuracy for MCC tablets. A less accurate
      subdivision was observed in tablets prepared with a DCP-MCC combination; this
      finding could be attributed to irregular binder distribution in this matrix. An
      optimized response was built using desirability analysis. This study helps to
      illuminate the relationship between fillers and binders to guide formulation
      scientists in the development of tablets with better subdivision performance.

PMID- 30120695
TI  - Using Manufacturing Design Space Concepts for Stability Risk Assessment
      Gabapentin NIPTE/FDA Case Study.
AB  - A quantitative, model-based risk assessment process was evaluated using Bayesian
      parameter estimation to determine the posterior distribution of the probability
      of a model tablet formulation's (gabapentin) ability to meet end-of-expiry
      stability criteria-based manufacturing controls. Experimental data was obtained
      from an FDA-supported, multi-year project that involved researchers at nine
      universities working collaboratively with industrial and governmental scientists
      under the leadership of the National Institute for Pharmaceutical Technology and
      Education (NITPE). The risk assessment process involved the development of a
      design space manufacturing model and shelf life stability model that shared
      stability-related critical quality attributes (CQAs). Monte Carlo simulations of
      the design space and shelf life models that uses model parameter uncertainty to
      estimate the probability of shelf life failure as a function of manufacturing
      control. The resultant linked design space and shelf life stability models were
      tested by comparing model predicted and observed long-term stability data
      generated under a variety of pilot scale production conditions.

PMID- 30120697
TI  - Proportionate palliative sedation and the giving of a deadly drug: the conundrum.
AB  - Among the oldest extant medical ethics, the Hippocratic Oath prohibits the giving
      of a deadly drug, regarding this act as an egregious violation of a medical ethic
      that is exclusively therapeutic. Proportionate palliative sedation involves the
      administration of a deadly drug. Hence it seems to violate the venerable
      Hippocratic promise associated with the dawn of Western medicine not to give a
      deadly drug. Relying on distinctions commonly employed in the analysis and
      evaluation of human actions, this article distinguishes physician-assisted
      suicide and euthanasia, as acts that necessarily violate the prohibition against
      giving a deadly drug, from proportionate palliative sedation, as an act that does
      not.

PMID- 30120696
TI  - Violence, research, and non-identity in the psychiatric clinic.
AB  - Violence in psychiatric clinics has been a consistent problem since the birth of
      modern psychiatry. In this paper, I examine current efforts to understand and
      reduce both violence and coercive responses to violence in psychiatry, arguing
      that these efforts are destined to fall short. By and large, scholarship on
      psychiatric violence reduction has focused on identifying discrete factors that
      are statistically associated with violence, such as patient demographics and
      clinical qualities, in an effort to quantify risk and predict violent acts before
      they happen. Using the work of Horkheimer and Adorno, I characterize the
      theoretical orientation of such efforts as identity thinking. I then argue that
      these approaches lead to epistemic imperceptiveness and a subtle form of
      conceptual restraint on patients. I suggest a reorientation in psychiatric
      research, away from identity thinking and toward a more productive and just
      approach to the problem of violence in psychiatric clinics.

PMID- 30120698
TI  - Diagnostic performance of 11C-choline PET/CT and FDG PET/CT for staging and
      restaging of renal cell cancer.
AB  - PURPOSE: To compare findings obtained with 11C-choline and FDG PET/CT scanning
      for renal cell carcinoma staging and restaging. MATERIALS AND METHODS: Twenty
      eight renal cell carcinoma patients whose histological subtype was clear cell
      type in 26 and papillary type in 2, while Fuhrman nuclear grade was G1,2 in 16
      and G3,4 in 12, underwent both 11C-choline and FDG PET/CT examinations before (n
      = 10) and/or after (n = 18) treatment, then those scanning modalities were
      compared in regard to patient- and lesion-based diagnostic performance using 5
      grading scores. Final diagnosis in each case was obtained based on
      histopathology, conventional radiological imaging, and clinical follow-up
      findings. The differences between 11C-choline and FDG PET/CT findings were
      evaluated using receiver-operating-characteristic (ROC) analysis and a McNemar
      test. RESULTS: Patient-based sensitivity, specificity, positive predictive,
      negative predictive, accuracy, and area under the ROC curve (AUC) values for 11C
      choline PET/CT for staging and restaging were 88.0% (22/25), 66.7% (2/3), 95.7%
      (22/23), 40.0% (2/5), 85.7% (24/28), and 0.887, respectively, while those for FDG
      PET/CT were 56.0% (14/25), 66.7% (2/3), 93.3% (14/15), 15.4% (2/13), 57.1%
      (16/28), and 0.647, respectively. Sensitivity, accuracy, and AUC were
      significantly different (p = 0.013, p = 0.013, p = 0.012, respectively). Among
      the 120 lesions, those with kidney, lung, lymph node, bone, pancreas, venous
      tumor thrombosis, adrenal gland, liver, or skin localization numbered 15, 64, 16,
      13, 4, 3, 2, 2, and 1, respectively. For all 120 lesions, 75 (62.5%) and 47
      (39.2%) were detected by 11C-choline and FDG PET/CT, respectively (p < 0.0001).
      CONCLUSION: For staging and restaging of renal cell carcinoma patients, 11C
      choline-PET/CT is significantly more useful than FDG-PET/CT.

PMID- 30120699
TI  - CFA Models with a General Factor and Multiple Sets of Secondary Factors.
AB  - We propose a class of confirmatory factor analysis models that include multiple
      sets of secondary or specific factors and a general factor. The general factor
      accounts for the common variance among manifest variables, whereas multiple sets
      of secondary factors account for the remaining source-specific dependency among
      subsets of manifest variables. A special case of the model is further proposed
      which constrains the specific factor loadings to be proportional to the general
      factor loadings. This proportional model substantially reduces the number of
      model parameters while preserving the essential structure of the general model.
      Furthermore, the proportional model allows for the interpretation of latent
      variables as the expected values of the observed manifest variables,
      decomposition of the variances, and the inclusion of interactions, similar to
      generalizability theory. We provide two applications to illustrate the utility of
      the proposed class of models.

PMID- 30120700
TI  - Comparison of central laboratory assessments of ER, PR, HER2, and Ki67 by
      IHC/FISH and the corresponding mRNAs (ESR1, PGR, ERBB2, and MKi67) by RT-qPCR on
      an automated, broadly deployed diagnostic platform.
AB  - PURPOSE: The methods (IHC/FISH) typically used to assess ER, PR, HER2, and Ki67
      in FFPE specimens from breast cancer patients are difficult to set up, perform,
      and standardize for use in low and middle-income countries. Use of an automated
      diagnostic platform (GeneXpert(r)) and assay (Xpert(r) Breast Cancer STRAT4) that
      employs RT-qPCR to quantitate ESR1, PGR, ERBB2, and MKi67 mRNAs from formalin
      fixed, paraffin-embedded (FFPE) tissues facilitates analyses in less than 3 h.
      This study compares breast cancer biomarker analyses using an RT-qPCR-based
      platform with analyses using standard IHC and FISH for assessment of the same
      biomarkers. METHODS: FFPE tissue sections from 523 patients were sent to a
      College of American Pathologists-certified central reference laboratory to
      evaluate concordance between IHC/FISH and STRAT4 using the laboratory's standard
      of care methods. A subset of 155 FFPE specimens was tested for concordance with
      STRAT4 using different IHC antibodies and scoring methods. RESULTS: Concordance
      between STRAT4 and IHC was 97.8% for ESR1, 90.4% for PGR, 93.3% for ERBB2
      (IHC/FISH for HER2), and 78.6% for MKi67. Receiver operating characteristic curve
      (ROC) area under the curve (AUC) values of 0.99, 0.95, 0.99, and 0.85 were
      generated for ESR1, PGR, ERBB2, and MKi67, respectively. Minor variabilities were
      observed depending on the IHC antibody comparator used. CONCLUSION: Evaluation of
      breast cancer biomarker status by STRAT4 was highly concordant with central
      IHC/FISH in this blinded, retrospectively analyzed collection of samples. STRAT4
      may provide a means to cost-effectively generate standardized diagnostic results
      for breast cancer patients in low- and middle-income countries.

PMID- 30120701
TI  - Genetic polymorphisms of 3'-untranslated region of SULT1A1 and their impact on
      tamoxifen metabolism and efficacy.
AB  - PURPOSE: Tamoxifen has a wide inter-variability. Recently, two SNPs in the 3'
      untranslated region (UTR) of the SULT1A1 gene, rs6839 and rs1042157, have been
      associated with decreased SULT1A1 activity. The aim of this study is to
      investigate the role of the rs6839 and rs1042157 on tamoxifen metabolism and
      relapse-free survival (RFS) in women diagnosed with early-breast cancer receiving
      tamoxifen. METHODS: Samples from 667 patients collected in the CYPTAM study
      (NTR1509) were used for genotyping (CYP2D6, SULT1A1 rs6839 and rs1042157) and
      measurements of tamoxifen and metabolites. Patients were categorized in three
      groups depending on the decreased SULT1A1 activity due to rs6839 and rs1042157:
      low activity group (rs6839 (GG) and rs1042157 (TT)); high activity group (rs6839
      (AA) and rs1042157 (CC)); and medium activity group (all the other combinations
      of rs6839 and rs1042157). Associations between SULT1A1 phenotypes and clinical
      outcome (RFS) were explored. RESULTS: In the low SULT1A1 activity group, higher
      endoxifen and 4-hydroxy-tamoxifen concentrations were found, compared to the
      medium and high activity group (endoxifen: 31.23 vs. 30.51 vs. 27.00, p value:
      0.016; 4-hydroxy-tamoxifen: 5.55 vs. 5.27 vs. 4.94, p value:0.05). In terms of
      relapse, the low activity group had a borderline better outcome compared to the
      medium and high SULT1A1 activity group (adjusted Hazard ratio: 0.297; 95% CI
      0.088-1.000; p value: 0.05). CONCLUSION: Our results suggested that rs6839 and
      rs1042157 SNPs have a minor effect on the concentrations and metabolic ratios of
      tamoxifen and its metabolites, and RFS in women receiving adjuvant tamoxifen.

PMID- 30120702
TI  - Cognitive-linguistic profiles of Chinese typical-functioning adolescent dyslexics
      and high-functioning dyslexics.
AB  - Dyslexia is a developmental disability affecting the acquisition of reading and
      writing skills, and its developmental nature makes longitudinal research of great
      importance. This study therefore investigated the cognitive-linguistic profiles
      of the typical-functioning dyslexics and high-functioning dyslexics with
      longitudinal cohorts of Chinese-speaking adolescents diagnosed with childhood
      dyslexia. These two dyslexic groups of fifty students (with 25 typical
      functioning dyslexics) were assessed in Grade 2 (Time 1) and in Grade 8 (Time 2),
      whereas 25 typically developing controls were assessed at Time 2. Students were
      administered measures of phonological awareness, morphological skills, visual
      orthographic knowledge, rapid naming, verbal working memory, and literacy skills.
      Results showed that, at Time 2, both dyslexic groups performed less well than the
      control group on most of the measures. Deficits in rapid naming were particularly
      salient in both dyslexic groups. Comparing the two dyslexic groups, the typical
      functioning dyslexics had more multiple deficits than the high-functioning
      dyslexics. Findings highlight the importance of rapid naming deficits as
      potential universal causes of dyslexia and the utility of targeting visual
      orthographic knowledge and morphological skills in supporting the development of
      dyslexic adolescents.

PMID- 30120704
TI  - The effect of perceptual information on output interference.
AB  - Retrieval from episodic memory has consequences (Malmberg, Lehman, Annis, Criss,
      & Shiffrin, The Psychology of Learning and Motivation, 61; 285-313, 2014). In
      some cases, the consequences are beneficial, as in the improvement in memory for
      items that were already retrieved (Izawa, 1970, Journal of Experimental
      Psychology, 83(2, Pt.1), 340-344; Izawa, Journal of Experimental Psychology,
      89(1): 10-21, 1971; Roediger & Karpicke, Psychological Science, 17(3), 249-255,
      2006). In other cases, the consequences are negative, as in the case of output
      interference (OI; Wickens, Borne, & Allen, Journal of Verbal Learning and Verbal
      Behavior, 2, 440-445, 1963). OI is the decrease in accuracy in episodic memory
      with increasing test trials. A release from OI is observed when accuracy rebounds
      following a switch in the category of item being tested (Criss, Salomao,
      Malmberg, Aue, Kilic, & Claridge, Quarterly Journal of Experimental Psychology,
      64(4): 316-326, 2018; Malmberg, Criss, Gangwani, & Shiffrin, Psychological
      Science, 23(2): 115-119, 2012). In all reports thus far, a release from OI was
      observed when the conceptual information of stimuli was switched. Here, we
      evaluate the possibility that changing perceptual information causes a release
      from OI by presenting items in two perceptual forms (image, audio recording or
      printed text of the corresponding word) either mixed or blocked at test. A
      release from OI was observed only for images. We discuss the roles of conceptual
      and perceptual information in producing OI within the retrieving effectively from
      memory modeling framework.

PMID- 30120705
TI  - Biosimilar Knowledge Among Oncology/Hematology Team Members in Colorado, USA: An
      Educational Initiative and Follow-Up Survey.
AB  - BACKGROUND: No data exist regarding oncology/hematology team members' knowledge
      of and views on biosimilars in Colorado, USA. Published research has suggested
      that health professionals may have a poor understanding of many issues related to
      biosimilars. OBJECTIVES: Our goal was to increase oncology/hematology team
      members' knowledge of biosimilars and then use an anonymous online survey to
      assess the knowledge gained. We also aimed to examine oncology/hematology team
      members' overall interest in the subject and their motivation to learn more about
      biosimilars in the future. METHODS: In phase I of the project, we developed
      printed materials covering many topics related to biosimilars, such as
      definition, regulation, and interchangeability, and the potential of biosimilars
      in optimal combination therapy for cancer. We distributed our brochures to each
      participating oncology/hematology office in Colorado. The oncology/hematology
      team members were then asked to complete the survey. RESULTS: A total of 62 team
      members responded to our survey. Nearly three-quarters of participants were
      oncology nurses or oncology nurse practitioners. More than 90% of survey
      respondents identified correct answers about the definition, regulations,
      interchangeability, safety, cost issues, and use of biosimilars in oncology and
      in older patients with cancer. Overall, and compared with those who had low
      levels of interest and motivation, significantly more (p < 0.05) study
      participants were interested in the subject of biosimilars [57 (92%) vs. 5 (8%)],
      motivated to learn more about them [59 (95%) vs. 3 (5%)], and interested in
      sharing information about biosimilars with colleagues and patients [51 (82%) vs.
      11 (18%)]. CONCLUSION: Our results demonstrate that oncology/hematology team
      members participating in our study became familiar with many important issues
      related to biosimilars. Many survey respondents were highly motivated to
      participate in future training focused on biosimilars, which should pave the way
      for new educational projects in the area.

PMID- 30120703
TI  - Ultrasound imaging of the anorectal malformation during the neonatal period: a
      comprehensive review.
AB  - Anorectal malformation (ARM) is classified as low, intermediate, or high;
      accurate diagnosis of the type during the early neonatal period is important to
      determine the appropriate initial surgical approach. This review assesses the
      role of ultrasound examination in the classification of ARM during the neonatal
      period, with a focus on landmarks on the sonogram, the approach used for
      sonography, and the optimal examination timing. The following three factors on
      the sonogram are used for the classification: location of the fistula, the
      distance between the distal rectal pouch and the anal dimple (perineum) (P-P
      distance), and the relationship between the puborectalis muscle and the distal
      rectal pouch. Three approaches can be used to evaluate ARM by ultrasonography,
      namely, suprapubic, perineal, and infracoccygeal approaches. Each approach has
      its own advantages and disadvantages. Optimal timing of the ultrasound
      examination is also important with respect to each factor to classify ARM. We
      have described the pitfalls of ultrasound in diagnosis of cases, namely ARM with
      Down syndrome (which tends to be without fistula), ARM with low birth weight, ARM
      with unusual location of fistula, ARM with opened fistula (where the P-P distance
      is unreliable), and cloacal malformation (variation of the high-type ARM).

PMID- 30120707
TI  - Spirulina supplementation during the transition period by grazing dairy cattle at
      tropical highland conditions.
AB  - The objective of this experiment was to evaluate the effects of spirulina
      supplementation on oxidative stress, immunity, and productive performance during
      the transition period by grazing dairy cattle. Thirty multiparous gestating cows
      with an initial body weight (BW = 544 +/- 57 kg) were enrolled in this experiment
      and were stratified by expected calving date. Cows were randomly assigned to one
      of the three experimental groups: (1) control, no supplementation of spirulina;
      (2) spirulina-15 (15 g/day of spirulina); and (3) spirulina-30 (30 g/day of
      spirulina). Body weight and body condition score (BCS) were recorded and blood
      samples were collected at - 21, 1, and 14 days, relative to calving. The day of
      parturition, colostrum and blood samples from calves were collected to measure
      IgG concentrations. After parturition milk yield, milk components and somatic
      cell count were monitored. Body weight, BW loss, BCS, and total antioxidant
      capacity were not affected by spirulina supplementation (P > 0.23) at any time
      point measured. Milk yield, milk components, and somatic cell count were not
      altered by treatment (P > 0.13). Results from this experiment suggest neither
      positive nor negative effects of spirulina supplementation on oxidative stress
      and productive performance during the transition period.

PMID- 30120706
TI  - Do vaccination interventions have effects? A study on how poultry vaccination
      interventions change smallholder farmer knowledge, attitudes, and practice in
      villages in Kenya and Tanzania.
AB  - Poultry are important for many poor households in developing countries, but there
      are many constraints to poultry production, including disease. One of the most
      important diseases of chickens is Newcastle disease (ND). Even though there are
      effective vaccines against this disease available in most countries, uptake by
      small-scale poultry keepers is often low. In this study, two areas in Kenya and
      Tanzania were studied, where some villages had received additional support to get
      vaccination and other villages had not. In Kenya, 320 households from 10 villages
      were interviewed, of which half of the villages had active promotion of
      vaccination through village-based advisors. In Tanzania, 457 households were
      interviewed, of which 241 came from villages that have had active support through
      either a project or government extension services. Knowledge about vaccines and
      the attitudes towards vaccinating against ND was evaluated using mixed
      multivariable logistic models. Results indicate that in Kenya, the most important
      determinants for understanding the function of a vaccine were having had support
      in the village and to have knowledge about ND signs, while in Tanzania gender and
      previous vaccine use were important in addition to having had support. Attitudes
      towards vaccination were mainly determined by knowledge, where more knowledge
      about how vaccines work in general or about ND contributed to more positive
      attitudes. Among Kenyan farmers that had never used the vaccine before, the
      amount of birds they lost to disease and predators also influenced attitudes. In
      conclusion, this study supports the notion that knowledge is a very important
      component of extension support and that simply making vaccines available may not
      be sufficient for high levels of uptake.

PMID- 30120709
TI  - LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of
      MiR-128-3p/GREM1 Axis and BMP Signaling Pathway.
AB  - The current research was aimed at probing into the role of long noncoding RNA
      (lncRNA) PVT1 in the pathogenesis of glioma and the regulatory mechanism of
      PVT1/miR-128-3p/GREM1 network in glioma via regulation of the bone morphogenetic
      protein (BMP) signaling pathway. Microarray analysis was used for preliminary
      screening for candidate lncRNAs and mRNAs in glioma tissues. Real-time
      quantitative polymerase chain reaction, Western blot, MTT assay, flow cytometry,
      migration and invasion assays, and xenograft tumor model were utilized to examine
      the influence of the lncRNA PVT1/miR-128-3p/GREM1 network on the biological
      functions of glioma cells. Luciferase assay and RNA-binding protein
      immunoprecipitation assay were used to validate the miR-128-3p-target
      relationships with lncRNA PVT1 or GREM1. In addition, the impact of GREM1 on BMP
      signaling pathway downstream proteins BMP2 and BMP4 was detected via Western
      blot. LncRNA PVT1 was highly expressed in human glioma tissues and significantly
      associated with WHO grade (I-II vs III-IV; p < 0.05). There existed a regulatory
      relationship between lncRNA PVT1 and miR-128-3p as well as that between miR-128
      3p and GREM1. MiR-128-3p was downregulated, whereas GREM1 was upregulated in
      glioma tissues in comparison with para-carcinoma tissues. Overexpression of GREM1
      promoted the proliferation and metastatic potential of glioma cells, whereas miR
      128-3p mimics inhibited the glioma cell activity through targeting GREM1.
      Furthermore, lncRNA PVT1 acted as a sponge of miR-128-3p and, thus, influenced
      the BMP signaling pathway downstream proteins BMP2 and BMP4 through regulating
      GREM1. LncRNA PVT1 modulated GREM1 and BMP downstream signaling proteins through
      sponging miR-128-3p, thereby promoting tumorigenesis and progression of glioma.

PMID- 30120708
TI  - CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: Transforming the Treatment
      of Relapsed and Refractory Disease.
AB  - PURPOSE OF REVIEW: Genetically engineered T cells expressing a chimeric antigen
      receptor (CAR-T) targeting specific antigens present on acute lymphoblastic
      leukemia (ALL) blasts have generated promising results in children and adults
      with relapsed and refractory disease. We review the current evidence for CAR-T
      cell therapy in ALL, associated toxicities, and efforts to improve durable
      response to therapy. RECENT FINDINGS: CD19-directed CAR-T cells have recently
      been approved by the FDA for use in children and young adults with ALL and in
      adults with diffuse large B cell lymphoma (DLBCL) in the relapsed/refractory
      setting. CD22-directed CAR-T cells have shown efficacy against leukemia as well
      in a recent clinical trial, representing the first alternative CAR target to
      approach comparable efficacy to CD19 CAR-T cells. Standardization of toxicity
      grading and management, strategies to combat significant relapse rates after CAR
      T therapy, and applicability of CAR-T cells to treat central nervous system (CNS)
      disease remain challenges in the field and represent priorities for continued
      research. CAR-T cells are a feasible, effective, and rapidly evolving therapy for
      patients with relapsed and refractory B cell malignancies.

PMID- 30120710
TI  - Irish Endocrine Society 42nd Annual Meeting, 19th and 20th October 2018.

PMID- 30120711
TI  - Evaluation of enterococci for potential probiotic utilization in dogs.
AB  - Some strains of the genus Enterococcus are effective probiotic bacteria if they
      meet safety and probiotic criteria. In our study, 17 canine enterococci
      previously selected from a group of 160 isolates based on safety criteria were
      screened for some functional properties relevant to their use as probiotics. The
      results of antimicrobial resistance testing showed sensitivity of eleven strains
      to EFSA recommended antimicrobials. In contrast, the most frequent resistance was
      observed for cefotaxim (15/17) and oxacillin (13/17). PCR detection of resistance
      genes (vanA, vanB, vanC, tetM, tetL, ermB, and mefA) revealed the presence of
      mefA gene in five Enterococcus faecium strains and vanA gene in one strain. The
      production of enzymes commonly associated with intestinal diseases was in general
      rare (beta-glucosidase 2/17, alpha-chymotrypsin 1/17, N-acetyl-beta
      glucosaminidase 0/17, and beta-glucuronidase 0/17). The measurement of strain
      survival rate (%) under the conditions simulating gastric (pH 2.5) and bile
      juices (0.3% bile) showed considerable differences between strains (< 0.01 to
      4.7% after 90 min for gastric juices, 48.0 to 254.0% after 180 min for bile). The
      concentration of produced L-lactic acid ranged between 83.1 to 119.3 mmol/L after
      48 h cultivation depending on the strain. All strains fermented 16 out of 49
      different carbohydrates (range from 17 to 23/49). Antimicrobial activity was
      recorded for two strains against some species of Listeria sp. and Enterococcus
      sp. Finally, two E. faecium candidates (IK25 and D7) were selected for testing in
      dogs, and hereafter they could possibly extend the currently limited range of
      beneficial bacteria of canine origin used as a dietary supplement for dogs.

PMID- 30120712
TI  - The Role of miR-150 in Stress-Induced Anxiety-Like Behavior in Mice.
AB  - Stress plays a crucial role in several psychiatric disorders, including anxiety.
      However, the underlying mechanisms remain poorly understood. Here, we used acute
      stress (AS) and chronic restraint stress (CRS) models to develop anxiety-like
      behavior and investigate the role of miR-150 in the hippocampi of mice.
      Corticosterone levels as well as glutamate receptors in the hippocampus were
      evaluated. We found that anxiety-like behavior was induced after either AS or
      CRS, as determined by the open-field test (OFT) and elevated plus-maze test
      (EPM). Increased corticosterone levels were observed in the blood of AS and CRS
      groups, while the expression of miR-150 mRNA in the hippocampus was significantly
      decreased. The expressions of GluN2A, GluR1, GluR2, and V-Glut2 in the
      hippocampus were decreased after either AS or CRS. Hippocampal GAD67 expression
      was increased by AS but not CRS, and GluN2B expression was decreased by CRS but
      not AS. Adult miR-150 knockout mice showed anxiety-like behavior, as assessed by
      the OFT and EPM. The expressions of GluN2A, GluN2B, GluR1, and GluR2 were also
      downregulated, but the expression of V-Glut2 was upregulated in the hippocampi of
      miR-150 knockout mice compared with wild-type mice. Interestingly, we found that
      the miR-150 knockout mice showed decreased dendrite lengths, dendrite branchings,
      and numbers of dendrite spines in the hippocampus compared with wild-type mice.
      These results suggest that miR-150 may influence the synaptic plasticity of the
      hippocampus and play a significant role in stress-induced anxiety-like behavior
      in adult mice.

PMID- 30120713
TI  - The Action of Di-(2-Ethylhexyl) Phthalate (DEHP) in Mouse Cerebral Cells Involves
      an Impairment in Aryl Hydrocarbon Receptor (AhR) Signaling.
AB  - Di-(2-ethylhexyl) phthalate (DEHP) is used as a plasticizer in various plastic
      compounds, such as polyvinyl chloride (PVC), and products including baby toys,
      packaging films and sheets, medical tubing, and blood storage bags.
      Epidemiological data suggest that phthalates increase the risk of the nervous
      system disorders; however, the impact of DEHP on the brain cells and the
      mechanisms of its action have not been clarified. The aim of the present study
      was to investigate the effects of DEHP on production of reactive oxygen species
      (ROS) and aryl hydrocarbon receptor (AhR), as well as Cyp1a1 and Cyp1b1 mRNA and
      protein expression in primary mouse cortical neurons and glial cells in the in
      vitro mono-cultures. Our experiments showed that DEHP stimulated ROS production
      in both types of mouse neocortical cells. Moreover, the results strongly support
      involvement of the AhR/Cyp1A1 signaling pathway in the action of DEHP in neurons
      and glial cells. However, the effects of DEHP acting on the AhR signaling
      pathways in these two types of neocortical cells were different. In neurons, AhR
      mRNA expression did not change, but AhR protein expression decreased in response
      to DEHP. A similar trend was observed for Cyp1a1 and Cyp1b1 mRNA and protein
      expression. Failure to induce Cyp1a1 in neurons was confirmed by EROD assay. In
      primary glial cells, a decrease in AhR protein level was accompanied by a
      decrease in AhR mRNA expression. In glial cells, mRNA and protein expression of
      Cyp1a1 as well as Cyp1a1-related EROD activity were significantly increased. As
      for Cyp1b1, both in neurons and glial cells Cyp1b1 mRNA expression did not
      significantly change, whereas Cyp1b1 protein level were decreased. We postulate
      that developmental exposure to DEHP which dysregulates AhR/Cyp1a1 may disrupt
      defense processes in brain neocortical cells that could increase their
      susceptibility to environmental toxins.

PMID- 30120714
TI  - XLIIIrd Sir Peter Freyer Memorial Lecture and Surgical Symposium.

PMID- 30120715
TI  - Detection of Molecular Alterations in Taiwanese Patients with Medullary Thyroid
      Cancer Using Whole-Exome Sequencing.
AB  - Genetic and epigenetic alterations are associated with the progression and
      prognosis of medullary thyroid carcinoma (MTC). We performed whole-exome
      sequencing of tumor tissue from seven patients with sporadic MTC using an
      Illumina HiSeq 2000 sequencing system. We conducted Sanger sequencing to confirm
      the somatic mutations in both tumor and matched normal tissues. We applied Kyoto
      Encyclopedia of Genes and Genomes functional enrichment analysis with the
      Database for Annotation, Visualization, and Integrated Discovery and STRING for
      pathway analysis. We detected new somatic mutations in the BICD2, DLG1, FSD2,
      IL17RD, KLHL25, PAPPA2, PRDM2, PSEN1, SCRN1, and TTC1 genes. We found a somatic
      mutation in the PDE4DIP gene that had previously been discovered mutated in other
      tumors but that had not been characterized in MTC. We investigated pathway
      deregulation in MTC. Data regarding 1152 MTCs were assembled from the Catalogue
      of Somatic Mutations in Cancer (COSMIC) and seven of our patients. Ontological
      analysis revealed that most of the variants aggregated in pathways that included
      the signaling pathways of thyroid cancer, central carbon metabolism, microRNAs in
      cancer, PI3K-Akt, ErbB, MAPK, mTOR, VEGF, and RAS. In conclusion, we conducted
      wide-ranging exome-wide analysis of the mutational spectrum of MTC in Taiwan's
      population and detected novel genes with potential associations with MTC
      tumorigenesis and irregularities in pathways that resulted in MTC pathogenesis.

PMID- 30120717
TI  - Analysis of the Thermal Stability of Very Thin Surface Layers of Corrosion
      Inhibitors by Time-of-Flight Secondary Ion Mass Spectrometry.
AB  - The powerful nature of the secondary ion mass spectrometry (SIMS) technique was
      explored in order to analyse very thin surface layers that were self-assembled on
      steel material from acidic solution. These surface layers are adsorbed corrosion
      inhibitors. The SIMS technique proved useful to characterise the molecular
      structure and homogeneity of thin surface layers in the nanometre range of
      specific analytes on the metallic substrate. Using SIMS, the thermal stability of
      these layers was further investigated and the desorption energy at a certain
      temperature was determined, where special attention was devoted to the method's
      static limit. In order to compare, and for certain cases emphasise, the benefits
      gained by using SIMS in such surface analysis compared with the X-ray
      photoelectron spectroscopy (XPS) method, the same samples were also analysed by
      means of the latter. XPS is usually considered to be the most powerful analytical
      tool in surface analysis studies, but, as shown herein, it has certain
      limitations compared to SIMS. Finally, the surface topography was investigated by
      employing atomic force microscopy (AFM) in order to carry out a comprehensive
      surface analysis. Graphical Abstract ?.

PMID- 30120716
TI  - The Heptahelical Domain of the Sweet Taste Receptor T1R2 Is a New Allosteric
      Binding Site for the Sweet Taste Modulator Amiloride That Modulates Sweet Taste
      in a Species-Dependent Manner.
AB  - The activity of sweet taste receptor (heterodimeric T1R2 and T1R3) can be
      modulated by sweet regulators. The compound amiloride can inhibit the sweet
      sensitivity of the human sweet taste receptor. This study describes the species
      dependent regulation of the response of sweet taste receptors by this sweet
      inhibitor. Amiloride inhibited the sweet taste response of humans and mice but
      not that of squirrel monkeys. Using human/squirrel monkey/mouse chimeric T1R2 and
      T1R3 receptors as well as the agonist perillartine (which can activate the single
      heptahelical domain of T1R2), we found that the heptahelical domain of T1R2 is
      the molecular determinant that mediates the species-dependent sensitivity to this
      sweet regulator. Compared to the sweet inhibitor lactisole (which acts on T1R3),
      amiloride has a different allosteric binding site on the sweet receptor, which is
      important new information for the design of novel sweet taste modulators that act
      on T1R2.

PMID- 30120718
TI  - Infectious disease services: a survey from four university hospitals in Germany.
AB  - PURPOSE: Involvement of infectious disease (ID) specialists in the care of
      hospitalized patients with infections through consultation services improves the
      quality of care and the outcome of patients. This survey aimed to describe
      activities and utilization of ID consultations at four German tertiary care
      hospitals. METHODS: A 1-month (March 2016) retrospective cross-sectional study at
      four university hospitals (Freiburg, Jena, Cologne and Regensburg) was performed.
      Only ID consultations with written documentation and bedside patient evaluation
      were included. Consultations were analyzed with regard to requesting departments,
      infections, case severity, and diagnostic and therapeutic recommendations.
      RESULTS: In the study period, 638 ID consultations were performed in 479 patients
      corresponding to 3-4 consultations per 100 inpatient cases. Patients were
      characterized by a high disease complexity-the mean case mix index in patients
      with consultation was 10.1 compared to 1.6 for all patients. ID consultations
      were requested by many different specialties, with approximately half of the
      requests coming from surgical disciplines. ID consultations resulted in revised
      diagnoses in 34% of the cases, provided recommendations for additional diagnostic
      procedures in 66%, and for modifications of antimicrobial regimens in 70% of the
      cases. CONCLUSIONS: Infectious disease consultations were requested for patients
      with severe and complicated diseases and resulted in recommendations that highly
      impacted the diagnostic work-up and therapeutic management of patients. The
      results of this survey may help to estimate requirements for establishment of
      such services in Germany.

PMID- 30120719
TI  - Malassezia in the central nervous system and multiple sclerosis.

PMID- 30120720
TI  - Laryngeal Epstein-Barr Virus-Associated Smooth Muscle Tumor in an Undernourished
      Child.
AB  - Smooth muscle tumors associated with Epstein-Barr virus infections (EBV-SMT) of
      laryngeal origin are exceedingly rare and have been reported in few adult
      patients, but not in children. This reported case describes a lesion found in the
      larynx of an 8-year-old Guatemalan undernourished girl. Microscopically, the
      lesion showed a highly cellular mesenchymal spindle cell tumor, containing
      frequent lymphocytes. The immunohistochemical analysis revealed positivity for
      alpha-smooth muscle actin and h-caldesmon. In addition, most of the tumor cells
      were positive for EBV by in situ hybridization. To the best of the author's
      knowledge, this is the first literature-reported case of laryngeal EBV-SMT
      occurring in an undernourished child.

PMID- 30120721
TI  - Identifying Candidate Biomarkers for Pleomorphic Adenoma: A Case-Control Study.
AB  - Pleomorphic adenoma (PA) is the most common benign salivary gland tumor.
      Kallikrein-related peptidases have been identified as biomarkers in many human
      tumors and may influence tumor behavior. We investigated KLK1-15 messenger
      ribonucleic acid and proteins in PA specimens to determine a KLK expression
      profile for this tumor. Fresh frozen PA tissue specimens (n = 26) and matched
      controls were subjected to quantitative real-time reverse transcription
      polymerase chain reaction to detect KLK1-15 mRNA. Expression of KLK1, KLK12,
      KLK13, and KLK8 proteins were then evaluated via immunostaining techniques.
      Statistical analyses were performed with the level of significance set at P <
      .05. We observed downregulation of KLK1, KLK12, and KLK13 mRNA expression, and
      immunostaining studies revealed downregulation of the corresponding proteins.
      Histologic evidence of capsular perforation was associated with increased KLK1
      protein expression. Tumor size was not associated with capsular invasion and/or
      perforation. This study is the first to detail a KLK expression profile for PA at
      both the transcriptional level and the protein level. Future work is required to
      develop clinical applications of these findings.

PMID- 30120722
TI  - Acute mesenteric ischaemia: a pictorial review.
AB  - Acute mesenteric ischaemia (AMI) is an uncommon cause of acute hospital admission
      with high mortality rates (50-90%) that requires early diagnosis and treatment.
      With the increase in average life expectancy, AMI represents one of the most
      threatening abdominal conditions in elderly patients. Untreated, AMI will cause
      mesenteric infarction, intestinal necrosis, an overwhelming inflammatory response
      and death. Early intervention can reverse this process leading to a full
      recovery, but the diagnosis of AMI is difficult. The failure to recognise AMI
      before intestinal necrosis has developed is responsible for the high mortality of
      the disease. Unfortunately, common CT findings in bowel ischaemia are not
      specific. Therefore, it is often a combination of nonspecific clinical,
      laboratory and radiological findings that helps most in the correct
      interpretation of CT findings. The purpose of this article is to provide an
      overview of the anatomy, physiology of mesenteric perfusion and discussions of
      causes, pathogenesis and CT findings in various types of acute bowel ischaemia.
      Familiarity with various imaging features of mesenteric injury is essential to
      make a timely diagnosis that will lead to improved patient outcomes. TEACHING
      POINTS: * AMI is a potentially life-threatening disorder whose prognosis depends
      on early recognition, accurate diagnosis and timely intervention. * Arterial
      inflow occlusion due to thrombosis or embolisation is the most common cause of
      AMI. * Four aetiological types of AMI have been associated with different
      characteristics and risk factors (EAMI, TAMI, VAMI and NOMI). * Physical
      examination and laboratory findings are not sensitive or specific for diagnosing
      AMI; therefore, MDCT is still the first-line imaging method in suspected AMI. *
      Although a number of scoring systems for prognosis have been proposed, these have
      not been validated in large-scale studies.

PMID- 30120725
TI  - Comment on: Substrate Metabolism During Ironman Triathlon: Different Horses on
      the Same Courses.

PMID- 30120726
TI  - Sources of Stress among Adults with Co-occurring Drug Use and Depressive
      Symptoms.
AB  - Stress, drug use, and depression are interconnected, but less is understood about
      sources of stress among adults with co-occurring drug use and depressive
      symptoms. The current study aimed to identify sources of stress and correlates
      among these adults. Data come from a cross-sectional baseline survey, including
      participants (n = 336) 18 to 55 years old, who reported past 6-month heroin or
      cocaine use and depressive symptoms. Exploratory factor analysis was conducted to
      identify sources of stress. Chi-square and multivariable Poisson regression with
      robust error variance were used to explore correlates of each factor. Three
      sources of stress were identified: financial stress related to drugs, stress due
      to community features, and stress involving a person's network. Past 6-month
      injection drug use (aPR = 1.34, 95% CI 1.07-1.67), perceived lack of control over
      drug use (aPR = 1.80, 95% CI 1.41-2.30), and difficulty abstaining from drug use
      (aPR = 1.55, 95% CI 1.22-1.97) were associated with an increased risk of high
      drug-related financial stress. Neighborhood disorder (aPR = 2.42, 95% CI 1.80
      3.24) and sleeping on the street (aPR = 1.37, 95% CI 1.04-1.80) were associated
      with an increased risk of high community-level stress. Past 6-month injection
      drug use (aPR = 1.28, 95% CI 1.04-1.58), perceived lack of control over drug use
      (aPR = 1.37, 95% CI 1.10-1.70), and drug use stigma was associated with an
      increased prevalence of high drug network stress (aPR = 1.32, 95% CI 1.05-1.65).
      Stress is a complex construct, including distinct sources and correlates. Further
      understanding of sources of stress is beneficial in recognizing potentially
      modifiable challenges faced by individuals who use drugs and experience
      depressive symptoms.

PMID- 30120724
TI  - Authors' Reply to Webster and Smith: Comment on: "Substrate Metabolism During
      Ironman Triathlon: Different Horses on the Same Courses".

PMID- 30120723
TI  - Ultrasound elastography: compression elastography and shear-wave elastography in
      the assessment of tendon injury.
AB  - Ultrasound elastography (USE) is a recent technology that has experienced major
      developments in the past two decades. The assessment of the main mechanical
      properties of tissues can be made with this technology by characterisation of
      their response to stress. This article reviews the two major techniques used in
      musculoskeletal elastography, compression elastography (CE) and shear-wave
      elastography (SWE), and evaluates the studies published on major electronic
      databases that use both techniques in the context of tendon pathology. CE
      accounts for more studies than SWE. The mechanical properties of tendons,
      particularly their stiffness, may be altered in the presence of tendon injury. CE
      and SWE have already been used for the assessment of Achilles tendons, patellar
      tendon, quadriceps tendon, epicondylar tendons and rotator cuff tendons and
      muscles. Achilles tendinopathy is the most studied tendon injury with USE,
      including the postoperative period after surgical repair of Achilles rupture
      tendon. In relation to conventional ultrasound (US), USE potentially increases
      the sensitivity and diagnostic accuracy in tendinopathy, and can detect
      pathological changes before they are visible in conventional US imaging. Several
      technical limitations are recognised, and standardisation is necessary to ensure
      repeatability and comparability of the results when using these techniques.
      Still, USE is a promising technique under development and may be used not only to
      promote an early diagnosis, but also to identify the risk of injury and to
      support the evaluation of rehabilitation interventions. KEY POINTS: * USE is used
      for the assessment of the mechanical properties of tissues, including the
      tendons. * USE increases diagnostic performance when coupled to conventional US
      imaging modalities. * USE will be useful in early diagnosis, tracking outcomes
      and monitoring treatments of tendon injury. * Technical issues and lack of
      standardisation limits USE use in the assessment of tendon injury.

PMID- 30120727
TI  - Any reward will do: Effects of a reverse-reward contingency on size preference
      with pet dogs (Canis lupus familiaris).
AB  - The reverse-reward contingency (RRC) task involves presenting subjects with a
      choice between one plate containing a large amount of food and a second plate
      containing a small amount of food. Subjects are then required to select the
      smaller of the two options in order to receive the larger-magnitude reward. The
      RRC task is a commonly used paradigm for assessing complex cognition, such as
      inhibitory control, in subjects. To date, the RRC task has not been tested with
      pet dogs as subjects, and it may provide insights to their ability to perceive
      quantities of differing magnitudes. Nine dogs were tested in an RRC task
      involving three conditions. In Condition 1, plates of food were presented, and
      the dogs were allowed to consume their choice. In Condition 2, plates with
      different-sized symbols resembling the quantities of food in Condition 1 were
      presented, and dogs received food quantities of the same size as their choice
      (e.g., a larger-magnitude reward for selecting the plate with the larger shape).
      In Condition 3, the same plates were presented, but dogs received a reverse-sized
      quantity of food, relative to their choice (e.g., a smaller-magnitude reward for
      selecting the plate with the larger shape). A novel addition here to the
      traditional RRC task was the inclusion of a third, empty (control) plate that was
      present throughout all conditions, and no programmed consequences were provided
      when that plate was selected. Our results were consistent with the previous RRC
      literature: All dogs developed and maintained a preference for the larger
      stimulus option across conditions. The use of symbolic representations did not
      ameliorate performance on the RRC task. Applied implications are discussed.

PMID- 30120729
TI  - Effects of organic-inorganic amendments on the cadmium fraction in soil and its
      accumulation in rice (Oryza sativa L.).
AB  - Cadmium (Cd) stress is a serious concern in agricultural soils worldwide, and
      increasing accumulation and subsequent transfer to humans via the food chain can
      have potentially harmful effects. In this study, field experiments were conducted
      to examine the uptake and translocation of Cd in rice, changes in the soil Cd
      speciation, and the subsequent effect on Cd accumulation in rice under combined
      organic (farmyard manure and crop straw) and inorganic (sepiolite, lime, and
      calcium-magnesium phosphate) soil amendments. The results showed that farmyard
      manure combined with sepiolite or lime and straw combined with lime or calcium
      magnesium phosphate reduced the Cd translocation from the rice roots to the straw
      and the grains, significantly decreasing the Cd accumulation in brown rice. In
      addition, straw combined with sepiolite, lime, or calcium-magnesium phosphate
      reduced the Cd accumulation in brown rice but increased the Cd translocation from
      the roots to the straw by 37.8-279.3% compared with the control. Organic
      inorganic amendments also decreased the soil exchangeable Cd and increased the
      organic-bound Cd by more than 40%. Fe-Mn oxide-bound Cd also increased but varied
      with growth. Cd accumulation in brown rice showed a significant positive
      relationship with soil exchangeable Cd at 90 days after transplantation, while at
      30 days, the increase in Fe-Mn oxide- and organic-bound Cd was found to be the
      key factor in reducing the Cd accumulation in rice. These findings suggest that
      straw (under rice-rape rotation) and farmyard manure (under rice-wheat rotation)
      combined with sepiolite or lime are widely applicable as agronomic control
      techniques aimed at lowering Cd pollution.

PMID- 30120728
TI  - Adsorption characteristics of methylene blue by biochar prepared using sheep,
      rabbit and pig manure.
AB  - Sheep manure biochar (SMB500), rabbit faeces biochar (RFB500) and pig manure
      biochar (PMB500) prepared by controlled thermal decomposition at 500  degrees C
      were used to adsorb methylene blue (MB) in water. Elemental analysis, BET and SEM
      results showed that the specific surface area, total pore volume and average pore
      diameter of SMB500 were 7.59, 4.20 and 1.16 times greater than those of RFB500,
      which were also 12.02, 6.88 and 1.37 times greater than those of PMB500,
      respectively. SMB500 had stronger stability and aromaticity. When the initial
      concentration of MB was 50 mg L-1 and pH was 11, adsorption achieved equilibrium
      at approximately 210 min. The adsorption followed pseudo-second-order kinetics
      (R2 > 0.96), indicating that liquid film diffusion, surface adsorption and
      intraparticle diffusion all contributed to the adsorption rate. The results of
      isothermal adsorption showed that the adsorption performance of SMB500 was more
      consistent with a Freundlich model, whereas the performance of RFB500 and PMB500
      was more consistent with a Langmuir model with a maximum adsorption capacity of
      53.68 to 238.31 mg g-1. Thermodynamic and FTIR studies showed that the adsorption
      of MB on SMB500, RFB500 and PMB500 was spontaneous and endothermic, and hydrogen
      bonds and pi-pi bonds were closely related to the adsorption process. The results
      of regeneration show that the optimal number of cycles for SMB500, RFB500 and
      PMB500 are 8, 5 and 3, respectively.

PMID- 30120730
TI  - Magnetic ion exchange resin for effective removal of perfluorooctanoate from
      water: study of a response surface methodology and adsorption performances.
AB  - This research exhibited the use of magnetic ion exchange (MIEX) resin as an
      effective adsorbent for the removal of perfluorooctanoate (PFOA) in aqueous
      solution. The adsorption performance of PFOA was investigated by a batch
      experiment. All kinds of factors affecting the adsorption of PFOA, including
      adsorbent dosage, initial concentration, adsorption time, temperature, stirring
      intensity, coexistent anions, initial solution pH, natural organic matter, ion
      strength, and bed volume were studied. Moreover, the response surface methodology
      was put into use to know the key parameters affecting PFOA removal efficiency.
      The sorption equilibrium and kinetic data could conform well to the Langmuir and
      pseudo-second-order model, respectively. Thermodynamic parameters were obtained,
      and it was observed that the adsorption of PFOA onto MIEX resin was an
      endothermic and spontaneous process at the temperatures under investigation. It
      was summarized that both chemical absorption and physical adsorption were
      involved in the PFOA sorption onto the MIEX resin. Moreover, the MIEX resin could
      be effectively regenerated using a saturated sodium chloride solution. A series
      of batch experiments and characterizations demonstrated that the MIEX resin
      possessed a strong adsorption ability with the removal efficiency exceeding 90%,
      allowing a possible practical application in future water treatment.

PMID- 30120731
TI  - Transcription Factor 2I Regulates Neuronal Development via TRPC3 in 7q11.23
      Disorder Models.
AB  - Williams syndrome (WS) and 7q11.23 duplication syndrome (Dup7q11.23) are
      neurodevelopmental disorders caused by the deletion and duplication,
      respectively, of ~ 25 protein-coding genes on chromosome 7q11.23. The general
      transcription factor 2I (GTF2I, protein TFII-I) is one of these proteins and has
      been implicated in the neurodevelopmental phenotypes of WS and Dup7q11.23. Here,
      we investigated the effect of copy number alterations in Gtf2i on neuronal
      maturation and intracellular calcium entry mechanisms known to be associated with
      this process. Mice with a single copy of Gtf2i (Gtf2i+/Del) had increased axonal
      outgrowth and increased TRPC3-mediated calcium entry upon carbachol stimulation.
      In contrast, mice with 3 copies of Gtf2i (Gtf2i+/Dup) had decreases in axon
      outgrowth and in TRPC3-mediated calcium entry. The underlying mechanism was that
      TFII-I did not affect TRPC3 protein expression, while it regulated TRPC3 membrane
      translocation. Together, our results provide novel functional insight into the
      cellular mechanisms that underlie neuronal maturation in the context of the
      7q11.23 disorders.

PMID- 30120732
TI  - Acute Ethanol Exposure Promotes Autophagy-Lysosome Pathway-Dependent ASIC1a
      Protein Degradation and Protects Against Acidosis-Induced Neurotoxicity.
AB  - Tissue acidosis is a common feature of brain ischemia which causes neuronal
      injury. Activation of acid-sensing ion channel 1a (ASIC1a) plays an important
      role in acidosis-mediated neurotoxicity. Acute ethanol administration has been
      shown to provide neuroprotective effects during ischemic stroke, but the precise
      mechanisms have yet to be determined. In this study, we investigated the effect
      of ethanol on the activity/expression of ASIC1a channels and acidosis-induced
      neurotoxicity. We showed that acute treatment of neuronal cells with ethanol for
      more than 3 h could reduce ASIC1a protein expression, ASIC currents, and acid
      induced [Ca2+]i elevation. We further demonstrated that ethanol-induced reduction
      of ASIC1a expression is mediated by autophagy-lysosome pathway (ALP)-dependent
      protein degradation. Finally, we showed that ethanol protected neuronal cells
      against acidosis-induced cytotoxicity, which effect was mimicked by autophagy
      activator rapamycin and abolished by autophagy inhibitor CQ. Together, these
      results indicate that moderate acute ethanol exposure can promote autophagy
      lysosome pathway-dependent ASIC1a protein degradation and protect against
      acidosis-induced neurotoxicity.

PMID- 30120733
TI  - Near Infrared Light Treatment Reduces Synaptic Levels of Toxic Tau Oligomers in
      Two Transgenic Mouse Models of Human Tauopathies.
AB  - Tau oligomers are emerging as a key contributor to the synaptic dysfunction that
      drives cognitive decline associated with the clinical manifestation and
      progression of Alzheimer's disease (AD). Accordingly, there is ample consensus
      that interventions that target tau oligomers may slow or halt the progression of
      AD. With this ultimate goal in mind, in the present study, we investigated tau
      oligomer accumulation and its synaptic and behavioral consequences after an in
      vivo treatment with near infrared (NIR) light (600-1000 nm) in two transgenic
      mouse models, overexpressing human tau either alone (hTau mice) or in combination
      with amyloid beta (3xTgAD mice). We found that a 4-week exposure to NIR light (90
      s/day/5 days a week) significantly reduced levels of endogenous total and
      oligomeric tau in both synaptosomes and total protein extracts from the
      hippocampus and cortex of hTau mice and improved deteriorating memory function.
      Similar results were observed in the 3xTgAD mice, which further displayed reduced
      synaptic Abeta after NIR light treatment. On the other hand, ex vivo binding of
      tau oligomers in isolated synaptosomes as well as tau oligomer-induced depression
      of long-term potentiation (LTP) in hippocampal slices from NIR light-treated wt
      mice were unaffected. Finally, levels of proteins critically involved in two
      mechanisms associated with clearance of misfolded tau, inducible HSP70 and
      autophagy, were upregulated in NIR light treated mice. Collectively, these
      results show that NIR light decreases levels of endogenous toxic tau oligomers
      and alleviate associated memory deficits, thus furthering the development of NIR
      light as a possible therapeutic for AD.

PMID- 30120734
TI  - Preconditioning and Cellular Engineering to Increase the Survival of Transplanted
      Neural Stem Cells for Motor Neuron Disease Therapy.
AB  - Despite the extensive research effort that has been made in the field, motor
      neuron diseases, namely, amyotrophic lateral sclerosis and spinal muscular
      atrophies, still represent an overwhelming cause of morbidity and mortality
      worldwide. Exogenous neural stem cell-based transplantation approaches have been
      investigated as multifaceted strategies to both protect and repair upper and
      lower motor neurons from degeneration and inflammation. Transplanted neural stem
      cells (NSCs) exert their beneficial effects not only through the replacement of
      damaged cells but also via bystander immunomodulatory and neurotrophic actions.
      Notwithstanding these promising findings, the clinical translatability of such
      techniques is jeopardized by the limited engraftment success and survival of
      transplanted cells within the hostile disease microenvironment. To overcome this
      obstacle, different methods to enhance graft survival, stability, and therapeutic
      potential have been developed, including environmental stress preconditioning,
      biopolymers scaffolds, and genetic engineering. In this review, we discuss
      current engineering techniques aimed at the exploitation of the migratory,
      proliferative, and secretive capacity of NSCs and their relevance for the
      therapeutic arsenal against motor neuron disorders and other neurological
      disorders.

PMID- 30120735
TI  - Degradation of Caytaxin Causes Learning and Memory Deficits via Activation of
      DAPK1 in Aging.
AB  - Loss of memory is an inevitable clinic sign in aging, but its underlying
      mechanisms remain unclear. Here we show that death-associated protein kinase
      (DAPK1) is involved in the decays of learning and memory in aging via degradation
      of Caytaxin, a brain-specific member of BNIP-2. DAPK1 becomes activated in the
      hippocampus of mice during aging. Activation of DAPK1 is closely associated with
      degradation of Caytaxin protein. Silencing Caytaxin by the expression of small
      interfering RNA (siRNA) that targets specifically to Caytaxin in the hippocampus
      of adult mice impairs the learning and memory. Genetic inactivation of DAPK1 by
      deletion of DAPK1 kinase domain prevents the degradation of Caytaxin and protects
      against learning and memory declines. Thus, activation of DAPK1 impairs learning
      and memory by degrading Caytaxin during aging.

PMID- 30120736
TI  - A Community-Partnered Approach to Developing Church-Based Interventions to Reduce
      Health Disparities Among African-Americans and Latinos.
AB  - Faith and public health partnerships offer promise to addressing health
      disparities, but examples that incorporate African-Americans and Latino
      congregations are lacking. Here we present results from developing a multi
      ethnic, multi-denominational faith and public health partnership to address
      health disparities through community-based participatory research (CBPR),
      focusing on several key issues: (1) the multi-layered governance structure and
      activities to establish the partnership and identify initial health priority
      (obesity), (2) characteristics of the congregations recruited to partnership (n =
      66), and (3) the lessons learned from participating congregations' past work on
      obesity that informed the development of a multi-level, multi-component, church
      based intervention. Having diverse staff with deep ties in the faith community,
      both among researchers and the primary community partner agency, was key to
      recruiting African-American and Latino churches. Involvement by local health
      department and community health clinic personnel provided technical expertise and
      support regarding health data and clinical resources. Selecting a health issue
      obesity-that affected all subgroups (e.g., African-Americans and Latinos, women
      and men, children and adults) garnered high enthusiasm among partners, as did
      including some innovative aspects such as a text/e-mail messaging component and a
      community mapping exercise to identify issues for advocacy. Funding that allowed
      for an extensive community engagement and planning process was key to
      successfully implementing a CBPR approach. Building partnerships through which
      multiple CBPR initiatives can be done offers efficiencies and sustainability in
      terms of programmatic activities, though long-term infrastructure grants,
      institutional support, and non-research funding from local foundations and health
      systems are likely needed.

PMID- 30120737
TI  - Inotersen: First Global Approval.
AB  - Ionis Pharmaceuticals and Akcea Therapeutics have developed inotersen
      (TegsediTM), an antisense oligonucleotide inhibitor of mutant and wild-type human
      transthyretin (TTR), for the treatment of hereditary transthyretin amyloidosis
      (hATTR). Mutation of the TTR gene results in accumulation of TTR protein
      fragments as amyloid deposits throughout the organs in patients with hATTR,
      including the peripheral nervous system and the heart. Treatment with inotersen,
      which selectively binds to TTR mRNA, prevents the synthesis of TTR protein in the
      liver, thus reducing further amyloid deposition throughout the body. Subcutaneous
      administration of inotersen significantly reduced neurological progression and
      improved health-related quality of life in patients with hATTR and polyneuropathy
      in a phase III trial. Based on these results, inotersen was recently approved in
      the EU for the treatment of stage 1 or 2 polyneuropathy in adult patients with
      hATTR and is under evaluation in the USA and Canada for a similar indication.
      This article summarizes the milestones in the development of inotersen leading to
      this first approval.

PMID- 30120738
TI  - Tecovirimat: First Global Approval.
AB  - Tecovirimat (TPOXX(r)) is an orthopoxvirus-specific antiviral drug developed by
      SIGA Technologies in conjunction with the US Department of Health and Human
      Services' Biomedical Advances Research and Development Authority. It acts by
      inhibiting the activity of the orthopoxvirus VP37 envelope wrapping protein,
      thereby preventing the formation of egress-competent enveloped virions, which are
      essential for dissemination of the virus in the host. In July 2018, oral
      tecovirimat was approved in the USA for the treatment of human smallpox disease
      caused by variola virus in adults and paediatric patients weighing >= 13 kg.
      Tecovirimat was approved under the US FDA's Animal Rule, in which marketing
      approval is based on its efficacy in relevant animal models. An intravenous
      formulation of tecovirimat is undergoing phase I development for the treatment of
      smallpox infection. This article summarises the milestones in the development of
      tecovirimat leading to this first approval for the treatment of human smallpox
      disease in adults and paediatric patients weighing >= 13 kg.

PMID- 30120739
TI  - Comment on: "Limited Evidence for Risk Factors for Proarrhythmia and Sudden
      Cardiac Death in Patients Using Antidepressants: Dutch Consensus on ECG
      Monitoring".

PMID- 30120740
TI  - Authors' Response to Braillon's Comment on: "Limited Evidence for Risk Factors
      for Proarrhythmia and Sudden Cardiac Death in Patients Using Antidepressants:
      Dutch Consensus on ECG Monitoring".

PMID- 30120741
TI  - Evaluation of Switching Patterns in FDA's Sentinel System: A New Tool to Assess
      Generic Drugs.
AB  - INTRODUCTION: Nearly 90% of drugs dispensed in the US are generic products.
      OBJECTIVE: The aim of this study was to develop and implement a tool for
      analyzing manufacturer-level drug utilization and switching patterns within the
      US Food and Drug Administration's Sentinel system. METHODS: A descriptive tool
      was designed to analyze data in the Sentinel common data model and was tested
      with two case studies-metoprolol extended release (ER) and lamotrigine ER-using
      claims data from four Sentinel data partners. We plotted initiators of each brand
      and generic product over time. For metoprolol ER, we evaluated rates of switching
      from generics around the time of manufacturing issues. For lamotrigine ER, we
      examined rates of switching back to the brand among those who switched from brand
      to generic. RESULTS: We identified 1,651,285 initiators of metoprolol ER products
      between July 2008 and September 2015. We observed a large decrease in monthly
      metoprolol ER initiators (from 25,465 in December 2008 to 13,128 in February
      2009), corresponding to recalls by generic manufacturers. We observed
      simultaneous increases in utilization of the authorized generic and brand
      products. We identified 4266 initiators of lamotrigine ER with an epilepsy
      diagnosis between January 2012 and September 2015. Among those who switched from
      brand to generic, the cumulative incidence of switching back was close to 20% at
      2 years. Switchback rates were higher for the first available generic products.
      CONCLUSIONS: This developed tool was able to elucidate novel utilization and
      switching patterns in two case studies. Such information can be used to support
      surveillance of generic drugs and biosimilars.

PMID- 30120744
TI  - The future today: new options for surgical care.

PMID- 30120745
TI  - Award winners 2018.

PMID- 30120742
TI  - Review and update: robotic transanal surgery (RTAS).
AB  - As the field of surgery advances, new approaches have allowed surgeons additional
      flexibility to perform further interventions with minimal or no external
      incisions. For many years, single site access (SSA) has been used for transanal
      procedures, and platforms allowing modified endoscopic approaches have been
      available. These platforms have limitations related to access, visualization,
      dexterity, camera control, and instrumentation. Recently, surgical robotics
      companies have developed and introduced new technologies and platforms, which may
      help address some of these limitations. Comprehensive internet, open access, and
      medical and industry conference reviews of robotic surgery platforms and
      technology available for use in SSA surgery were conducted and 30 articles were
      found using keywords "robotic surgery, transanal, single site, robotic transanal
      surgery". A PubMed, Medline, Journals @OVID and open access search for data
      related to these platforms and technologies was also performed yielding 11
      articles. Abstracts were reviewed for those written in the English language,
      leaving 40 articles which were then filtered for those pertaining to robotic
      surgery, transanal. 58 abstracts were found, duplicates were eliminated, and the
      remaining 35 articles were read in their entirety by two reviewers. Several new
      and existing platforms are identified for use in SSA surgery for transanal
      surgery as well as abdominal and transoral surgery. These are reviewed, including
      brand, features, approved and suggested uses, and potential limitations. New
      robotic technologies serve to enhance the ability of surgeons to perform SSA
      surgery. This next generation of robotic surgery technology overcomes some of the
      limitations of preceding endoscopic SSA surgery technology and will enhance the
      advancement of robotic transanal surgery, but outcomes and performance data are
      still limited.

PMID- 30120743
TI  - Sexual and urinary outcomes in robotic rectal surgery: review of the literature
      and technical considerations.
AB  - Several studies have reported high rates of urogenital dysfunction after open and
      laparoscopic surgery for rectal cancer. Robotic surgery has several features that
      could facilitate identification and preservation of autonomic nerves. This
      manuscript aims to summarize the literature regarding urogenital function after
      robotic rectal cancer surgery and focus on technical aspects of nerve-sparing
      total mesorectal excision. Comprehensive searches were conducted through online
      databases. Selection criteria included: original articles assessing urinary and
      sexual function after robotic surgery of males and/or females with standardized
      questionnaires. A total of 16 articles were included in the review. Seven of the
      nine cohort studies evaluating male sexual function showed earlier recovery or
      better outcomes in patients operated with robotic techniques. Two studies did not
      find any statistically significant difference. Three out of four case series
      found no difference in sexual function scores measured preoperatively and after 1
      year. Female sexual function was assessed in seven studies: two case series show
      no deterioration of at 1 year. Three comparative studies showed no difference
      between robotic and laparoscopic groups. Two randomized control trials showed
      different results in terms of male and female sexual functions with better
      preservation at 1 year in the robotic group in one and no difference in another.
      Urinary functions assessed in males and/or females in the 16 studies showed no
      statistically significant differences at long-term follow-up. At present, there
      is no evidence of superiority of robotic surgery for performing nerve-sparing
      rectal cancer surgery.

PMID- 30120747
TI  - What is This Image? 2018: Image 3.

PMID- 30120746
TI  - F-18 FDG PET for assessment of disease activity of large vessel vasculitis: A
      systematic review and meta-analysis.
AB  - BACKGROUND: The aim of this study is to investigate the performance of F-18
      fluorodeoxyglucose positron emission tomography (F-18 FDG PET) or positron
      emission tomography/computed tomography (PET/CT) for the assessment of disease
      activity in patients with large vessel vasculitis (LVV) through a meta-analysis.
      METHODS: The MEDLINE via PubMed and EMBASE were searched for the studies
      evaluating the performance of F-18 FDG PET or PET/CT in the assessment of disease
      activity in patients with LVV. Pooled sensitivity, specificity, diagnostic odds
      ratios (DORs), and summary receiver-operating characteristic (sROC) curve were
      estimated across the included studies. Possible publication bias was assessed by
      Deek's funnel plot asymmetry tests. RESULTS: A total of 439 PET images from 298
      patients pooled from nine studies showed that the pooled sensitivity was 0.88
      [95% confidence interval (CI) 0.79-0.93] without heterogeneity (chi2 = 14.42, P =
      .07) and the pooled specificity was 0.81 (95% CI 0.64-0.91) with heterogeneity
      (chi2 = 63.72, P = .00) for the detection of active LVV. The pooled DOR was 30
      (95% CI 8-107). Hierarchical sROC curve indicates that the area under the curve
      was 0.91 (95% CI 0.89-0.94). There was no significant publication bias (P = .42),
      and meta-regression analysis revealed that none of the variables was the source
      of the study heterogeneity. CONCLUSIONS: F-18 FDG PET has a good performance for
      the detection of active disease status in patients with LVV. Revised criteria for
      the assessment of disease activity incorporated with F-18 FDG PET or PET/CT
      should be introduced and validated. Further studies are warranted to determine if
      PET-based treatment of LVV can improve outcomes.

PMID- 30120748
TI  - Cardiac amyloidosis: The starched heart.

PMID- 30120749
TI  - The influence of anthropometric and basic circulatory variables on count rate in
      cadmium-zinc-telluride SPECT gated radionuclide angiography.
AB  - AIM: To determine the influence of weight, height, gender, age, heart rate, and
      blood pressure on count rate in cadmium-zinc-telluride single-photon emission
      computed tomography (CZT SPECT) gated radionuclide angiography. METHOD: A total
      of 1,065 eligible patients referred for routine assessment of left ventricular
      ejection fraction were registered from August 2015 to November 2016. Data were
      recorded on heart rate, systolic and diastolic blood pressure, age, gender,
      height, weight, and count rate. All radionuclide angiographies were performed on
      a dedicated cardiac CZT SPECT camera, GE Discovery 530c. A dose of 550 MBq 99mTc
      labeled human serum albumin was administered intravenously to each patient.
      RESULTS: Count rate varied from 1.2 to 8.9 counts per second. All test variables
      were significantly associated with count rate. From the preliminary analysis,
      weight appeared as the main contributing factor for explaining the variations in
      count rate with and R2 of 0.68. A model consisting of weight, height, gender, and
      age explains 75% of the variance in count rate. CONCLUSION: Patient height,
      weight, gender, and age have significant impact on count rate when performing CZT
      radionuclide angiography and may subsequently be used for individualized planning
      of tracer dosage.

PMID- 30120750
TI  - Selection of abstracts from the scientific sessions of the Society of Nuclear
      Medicine and Molecular Imaging, Philadelphia PA June 23-26, 2018.
AB  - This mini-review highlights cardiovascular studies that were presented during the
      2018 Society of Nuclear Medicine and Molecular Imaging (SNMMI) annual meeting in
      Philadelphia. The aim of this review is to inform readers about several
      noteworthy studies reported at the meeting. Although cardiovascular application
      of PET and SPECT are not the primary focus of the SNMMI, several scientific teams
      working in this field presented their latest scientific findings at this meeting.
      The review therefore aims to inform the readers who did not attend the SNMMI
      annual meeting about some interesting new concepts presented this year at the
      conference.

PMID- 30120751
TI  - Active Inference, Novelty and Neglect.
AB  - In this chapter, we provide an overview of the principles of active inference. We
      illustrate how different forms of short-term memory are expressed formally
      (mathematically) through appealing to beliefs about the causes of our sensations
      and about the actions we pursue. This is used to motivate an approach to active
      vision that depends upon inferences about the causes of 'what I have seen' and
      learning about 'what I would see if I were to look there'. The former could
      manifest as persistent 'delay-period' activity - of the sort associated with
      working memory, while the latter is better suited to changes in synaptic efficacy
      - of the sort that underlies short-term learning and adaptation. We review
      formulations of these ideas in terms of active inference, their role in directing
      visual exploration and the consequences - for active vision - of their failures.
      To illustrate the latter, we draw upon some of our recent work on the
      computational anatomy of visual neglect.

PMID- 30120752
TI  - The Evolution of Gaze Shifting Eye Movements.
AB  - In animals with good eyesight most eye movements consist of saccades, which
      rapidly shift the direction of the eye's axis, and intervals between the saccades
      (fixations) in which gaze is kept stationary relative to the surroundings. This
      stability is needed to prevent motion blur, and it is achieved by reflexes which
      counter-rotate the eye when the head moves. This saccade-and-fixate strategy
      arose early in fish evolution, when the original function of saccades was to re
      centre the eye as the fish turned. In primates, and other foveate vertebrates,
      saccades took on the new function of directing the fovea to objects of interest
      in the surroundings. Among invertebrates the same saccade-and-fixate pattern is
      seen, especially in insects, crustaceans and cephalopod molluscs.

PMID- 30120754
TI  - Persistence to Treatment with Novel Antidiabetic Drugs (Dipeptidyl Peptidase-4
      Inhibitors, Sodium-Glucose Co-Transporter-2 Inhibitors, and Glucagon-Like Peptide
      1 Receptor Agonists) in People with Type 2 Diabetes: A Nationwide Cohort Study.
AB  - INTRODUCTION: Adequate persistence to antidiabetic treatment is highly important
      to achieve proper glycemic control. In this study we evaluate the persistence to
      treatment with dipeptidyl peptidase-4 inhibitors, sodium-glucose co-transporter-2
      inhibitors, and glucagon-like peptide-1 receptor agonists in a nationwide cohort
      of patients with type 2 diabetes. METHODS: Using a central database in Hungary,
      we analyzed the persistence to the treatment with dipeptidyl peptidase-4
      inhibitors (n = 59,900), sodium-glucose co-transporter-2 inhibitors (n = 26,052),
      and glucagon-like peptide-1 receptor agonists (n = 17,332) at treatment
      intensification between 2014 and 2016. We also compared the persistence of
      dipeptidyl peptidase-4 inhibitors (n = 9163) and sodium-glucose co-transporter-2
      inhibitors (n = 1257) in initial therapy to that of metformin (n = 79,305) or
      sulfonylureas (n = 29,057). The rates of persistence to treatment and risk of non
      persistence are reported. RESULTS: The persistence rates of dipeptidyl peptidase
      4 inhibitors, sodium-glucose co-transporter-2 inhibitors, and glucagon-like
      peptide-1 receptor agonists at treatment intensification were 69.6%, 67.8%, and
      66.3% at year 1 which decreased to 57.3%, 56.8%, and 52.1% by year 2,
      respectively. The risk of non-persistence was higher by 6.6% (95% CI 3.6-9.6) for
      sodium-glucose co-transporter-2 inhibitors and by 8.3% (95% CI 5.0-11.5) for
      glucagon-like peptide-1 receptor agonists as compared to dipeptidyl peptidase-4
      inhibitors. Novel oral antidiabetic drugs in fixed versus free add-on
      combinations with metformin had higher persistence. The persistence to treatment
      with novel oral antidiabetic drugs in initial therapy was better (dipeptidyl
      peptidase-4 inhibitors, 59.6% and 47.6%; sodium-glucose co-transporter-2
      inhibitors, 61.9% and 47.0%) than that of initial monotherapy with metformin
      (47.0% and 39.1%) or sulfonylureas (52.4% and 41.8%) at years 1 and 2,
      respectively. CONCLUSION: Analysis of persistence of treatment with novel glucose
      lowering medications revealed differences between drug classes, favoring
      dipeptidyl peptidase-4 inhibitors vs. sodium-glucose co-transporter-2 inhibitors
      and glucagon-like peptide-1 receptor agonists. Persistence data of novel
      antihyperglycemic agents may be useful for guiding the decision at initiation of
      antidiabetic treatment. FUNDING: Hungarian Diabetes Association. Plain language
      summary available for this article.

PMID- 30120756
TI  - Fast Von Mises strain imaging on ultrasound carotid vessel wall by flow driven
      diffusion method.
AB  - The elasticity of the vessel wall is important for the clinical identification of
      rupture-risks. The Von Mises strain can be a potential index for the indication
      of carotid vessel pathologies. In this paper, a fast clinically applicable real
      time algorithm from time-sequence of B-mode carotid images is developed. Due to
      the compression induced by the normal cardiac pulsation, tissue motion occurs
      radially and non-rigidly. To obtain an accurate motion field, we developed a
      variational functional integrating the optical flow equation and an anisotropic
      regularizer, and designed a diffusion tensor to encourage coherence diffusion.
      The motion field is smoothed along the desired motion flow orientation. A fast,
      additive operator splitting scheme, which is ten times faster than the
      conventional discrete method, is used for the numerical implementation. To
      demonstrate the efficiency of the proposed approach, finite element models are
      set up for normal and pathological carotid vessel walls. The results indicate
      that the proposed diffusion approach obtains an accurate smooth and continuous
      motion field and greatly improves the follow up strain estimation using a fast
      differential strain filter. Furthermore, our approach using the Von Mises strain
      imaging on clinical ultrasound images of the carotid artery is validated.
      Participants above 65-years in age suffering from different stages of
      atherosclerosis in their carotid artery are selected. The results are evaluated
      by an experienced physician. The evaluation results demonstrate that the Von
      Mises strain has a good correspondence to the presence of certain suspicious
      areas in the B-mode images. The proposed method is therefore clinically
      applicable for the real-time Von Mises strain imaging of carotid vessel walls,
      and can be of great value as a complementary method to B-mode image for the
      clinical identification of the risk of plaque vulnerability.

PMID- 30120753
TI  - Patients' Perspectives of Oral and Injectable Type 2 Diabetes Medicines, Their
      Body Weight and Medicine-Taking Behavior in the UK: A Systematic Review and Meta
      Ethnography.
AB  - : The aim of this review is to identify peoples' perspectives of their glucose
      lowering and anti-obesity drugs in relation to diabetes and weight control and to
      explore how these views affect medication adherence. Theoretical perspectives
      associated with medicine-taking behavior are also explored. The systematic review
      was based on a meta-ethnography of qualitative studies identified through a
      search of 12 medical and social science databases and subsequent citation
      searches. The quality of all studies was assessed. Sixteen studies were included
      with data from 360 UK individuals. No relevant studies were identified which
      focused on anti-obesity and non-insulin injectable drugs. The review revealed
      that the patients' perspectives and emotional state were influenced by starting
      and/or changing to a new glucose-lowering medicine. These were also influenced by
      prior medication experience, disease perceptions and interactions with
      clinicians. Despite reports of positive experiences with and positive perceptions
      of medicines, and of participation in strategies to regain life control,
      medication non-adherence was common. Accepting glucose-lowering medicines
      impacted on the individual's perception of lifestyle changes, and it was notable
      that weight loss was not perceived as a strategy to support diabetes management.
      Synthesis revealed that more than one theory is required to explain medicine
      taking behavior. New insights into the underlying factors of poor adherence and
      the specific practical issues identified in this review can help in the
      development of patient-centered interventions. FUNDING: Diabetes UK.

PMID- 30120755
TI  - Diabetes Management and Healthcare Resource Use When Intensifying from Basal
      Insulin to Basal-Bolus: A Survey of Type 2 Diabetes Patients.
AB  - INTRODUCTION: Currently, there is limited knowledge about the experiences and
      challenges type 2 diabetes (T2D) patients face when intensifying from basal
      insulin to more complex regimens. The purpose of this study was to examine the
      experiences of adults with T2D who have been intensified to a basal-bolus insulin
      regimen, including challenges related to intensification, medication adherence
      issues, non-persistence, and healthcare resource use related to intensification.
      METHODS: A web-based survey of adults diagnosed with T2D and currently treated
      with basal insulin was conducted in the UK and the USA. The analysis sample was
      restricted to respondents with current/recent basal-bolus treatment (n = 398) and
      divided into three analysis groups: (1) "basal-bolus adherent" (current basal
      bolus treatment with at least 90% adherence); (2) "basal-bolus non-adherent"
      (current basal-bolus treatment with less than 80% adherence); and (3) "stopped
      bolus" (discontinued bolus in past 12 months). RESULTS: Basal-bolus non-adherent
      respondents reported fewer discussions with their healthcare providers (HCPs)
      before starting bolus and more frequent difficulties with and worries about
      taking bolus insulin compared to basal-bolus adherent and stopped bolus groups.
      The most frequently reported reasons for discontinuing bolus were related to the
      complicated nature of regimen, including too complicated to calculate bolus doses
      (25.7%), too complicated to regulate food in relation to bolus (20.7%), and too
      complicated to keep track of taking two different insulins (18.6%). Respondents
      who stopped bolus reported more frequent HCP visits related to diabetes compared
      to the basal-bolus adherent and basal-bolus non-adherent groups. CONCLUSION:
      Results suggest that the complicated nature of basal-bolus therapy contributes to
      the difficulties that T2D patients have with the regimen and to non-persistence.
      Physician and patient education may help patients address these treatment
      challenges to improve basal-bolus adherence and persistence, which could reduce
      healthcare resource use and costs. Less complex regimens may be appropriate for
      patients with persistent treatment difficulties. FUNDING: Novo Nordisk A/S.

PMID- 30120758
TI  - Oncological and Functional Outcomes of Laparoscopic Radiofrequency Ablation and
      Partial Nephrectomy for T1a Renal Masses: A Retrospective Single-center 60 Month
      Follow-up Cohort Study.
AB  - PURPOSE: It remains unclear whether laparoscopic radiofrequency ablation (RFA)
      for primary treatment of small renal masses is similar to partial nephrectomy
      (PN) in terms of long-term oncological and renal function outcomes. We reviewed
      the long-term outcomes for patients with T1a renal masses treated with either
      laparoscopic RFA or PN. MATERIALS AND METHODS: This retrospective single-center
      study on 115 patients who were treated by laparoscopic RFA or PN for small (<4
      cm) renal masses between January 2005 and October 2014 was performed at Chungnam
      National University Hospital. Estimated glomerular filtration rate (eGFR) was
      measured before and 1-2 weeks after surgery and at last follow-up. The
      laparoscopic RFA and PN groups were compared in terms of clinical characteristics
      data and change in eGFR after surgery using the Chi-squared test or Student's t
      test. Survival data were analyzed using the Kaplan-Meier method and the log-rank
      test. RESULTS: Of the 115 patients, 62 and 53 underwent laparoscopic RFA and PN,
      respectively. Their mean (range) follow-up duration was 60 (30-104) and 68 (30
      149) months, respectively (p=0.092). The RFA patients were older (p=0.023) and
      had smaller tumors (p=0.000). RFA associated with shorter operation and
      hospitalization times and less perioperative blood loss (all p=0.000). The groups
      did not differ in terms of change in eGFR 1-2 weeks after surgery (p=0.252) or at
      the last follow-up (p=0.395) or 5 year survival rates (p=0.360). CONCLUSION:
      Laparoscopic RFA for small renal masses was comparable to PN in terms of
      oncological and functional outcomes and associated with shorter operative and
      hospitalization times and less perioperative bleeding.

PMID- 30120757
TI  - Assessment of electron density effects on dose calculation and optimisation
      accuracy for nasopharynx, for MRI only treatment planning.
AB  - Computed tomography (CT) is the gold standard for radiotherapy simulation and
      treatment planning, providing spatial accuracy, bony anatomy definition and
      electron density information for dose calculations. Magnetic resonance imaging
      (MRI) has been introduced in radiotherapy to improve visualisation of anatomy for
      accurate target definition and contouring, however lacks electron density
      information required for dose calculations, with various methods used to overcome
      this. The aim of this work is to assess the impact on dose calculation accuracy
      and optimisation results of different approaches to determine electron density,
      as could be used in MRI only treatment planning for nasopharyngeal datasets with
      VMAT treatment plans. Volumetric modulated arc therapy (VMAT) plans were created
      for 10 retrospective head and neck (H&N) nasopharyngeal patients. The VMAT plans
      were generated on the gold standard dataset, the original CT scan. Data sets with
      no density correction (water equivalent) and two different sets of bulk density
      correction for bone/air/tissue applied separately were generated for these
      patients and the VMAT plans were recalculated for each case. Plans were also
      reoptimised on these data sets, and recalculated. Optimisation error was assessed
      through equivalent uniform dose (EUD) differences. Additionally, point dose
      comparison, dose volume histogram (DVH) analysis and gamma analysis of dose were
      used to assess dose calculation error. The dose calculation error on average was
      an increase in EUD whereas the optimisation error on average was a reduction in
      EUD compared to the original plan for all datasets aside from the bone only
      override dataset where bone was set to 1.61 g/cm3. For the optimisation error,
      the largest mean absolute error (MAE) was 1.88 Gy EUD for the PTV, and 2.21 Gy
      EUD for the brainstem, for the reoptimisation completed on the air only
      overridden dataset, and recalculated on the original. Bulk density corrections
      for bone and air provide dose calculations within 3% of the original treatment
      plans. Optimisation errors have the potential to be greater than dose calculation
      errors if incorrect density corrections are utilized. Electron density correction
      using a bulk density approach achieves dose calculation uncertainties within 3%,
      however more advanced approaches, such as a voxel based approach, may improve
      accuracy and should be considered.

PMID- 30120759
TI  - Comparison of Alpha-Blockers and Antimuscarinics in Improving Ureteral Stent
      Related Symptoms: A Meta-Analysis.
AB  - OBJECTIVE: A meta-analysiswas conducted to compare alpha-blocker and
      antimuscarinic monotherapies in releasing US-related symptoms. METHOD: A
      comprehensive literature search was performed on online databases PubMed, Web of
      Science, Medline, and Cochrane library. Ureteric Symptom Score Questionnaire
      (USSQ), International Prostate Symptom Score (IPSS), quality of life (QoL) and
      visual analogue pain scale (VAPS) were pooled and compared. Statistical
      significance was taken as two-sided p<0.05. RESULTS: Nine full-text articles met
      the inclusion criteria and have beenincluded. The studies were conducted in 9
      different centers between 2009 and 2016. All articles were RCT studies and a
      total of 654 patients were recorded totally, among which 323 were given alpha
      blockers while others were given antimuscarinics. Although patients using alpha
      blockers presented lower USSQ scores, no statistically significant difference was
      recorded in urinary symptom(SMD 0.5, 95 % CI -0.2 to 1.20, P=0.159), pain(SMD
      0.33, 95 % CI -0.26 to 0.92, P=0.280),general health,work performance(SMD-0.34,
      95 % CI -0.08 to 0.76, P=0.115)  and sexual performance  (all p>0.05)(SMD 0.12,
      95 % CI -0.10 to 0.34, P=0.280). Meanwhile IPSS(SMD -0.10, 95 % CI -0.32 to 0.11,
      P=0.358), QoL(SMD-0.03, 95 % CI -0.23 to 0.18, P=0.802)  and VAPS(SMD 0.08, 95 %
      CI -0.15 to 0.31, P=0.447) were similar between the two groups (all p>0.05).
      CONCLUSIONS: The analysis suggests that AB showed a similar effect with AM. It is
      necessary to conduct a larger and more detailed cohort study and find the
      population that potentially might benefit most by AM.

PMID- 30120760
TI  - The Effects of Nocturnal Blood Pressure Paterns and Autonomic Alterations on
      Erectile Functions in Patients with Hypertension.
AB  - PURPOSE: Hypertension (HT) is known to be of the main risk factors for erectile
      dysfunction (ED). But non-dipping (<%10 drop in the night) of HT is not
      investigated truly. The aim of this study was to test the hypothesis that the non
      dipper hypertensive patients are more prone to develop erectile dysfunction.
      MATERIALS AND METHODS: This was a cross-sectional clinical study. 70 HT patients
      diagnosed by Ambulatory blood pressure monitoring (ABPM) were classified into 3
      groups (No ED, mild to moderate and severe) according to their International
      Index of Erectile Function (IIEF) scores. All three groups were compared for
      their dipping status by ABPM, heart rate variability (HRV) by holter monitoring.
      RESULTS: In our study non-dipper hypertensives had statistically more erectile
      dysfunction (P=0.004). Also severe ED patients with non-dipping pattern had
      decreased dipping blood pressure levels then those of ED(-) patients with non
      dipping HT (P= .003)(Daytime Systolic/Nighttime Diastolic Blood Pressure= 0.8 +/-
      0.07 / 3.90 +/- 1.5, respectively). LF/HF daytime/ nighttime in holter reflecting
      sympathetic overactivity (P< .001). CONCLUSION: Autonomic dysfunction especially
      sympathetic overactivity is associated with both non dipping pattern of HT and
      erectile dysfunction as a common pathologic pathway, besides there might be an
      association between ED and non dipping HT.

PMID- 30120761
TI  - Primary hyperaldosteronism induced by aldosterone-producing adenoma co-existing
      with a left suprarenal accessory spleen: two case reports and a review of the
      literature.
AB  - We encountered 2 patients (a 33-year-old woman and a 66-year-old man) with an
      aldosterone-producing adenoma (APA) and a left accessory spleen. The patients'
      primary symptoms were hypertension and hypokalemia, and both had elevated serum
      aldosterone levels. Preoperative computed tomography a left suprarenal
      retroperitoneal mass and laparoscopic left adrenalectomy was performed in both
      cases. The postoperative microscopic examination revealed splenic tissue. Both
      patients experienced relief of their hypertension and hypokalemia, with an
      uneventful recovery.

PMID- 30120762
TI  - The Prevalence of Redo-Ureteroneocystostomy and Associated Risk Factors
      inPediatric Vesicoureteral Reflux Patients Treated with Ureteroneocystostomy.
AB  - PURPOSE: The aim of the study was to examine the prevalence of redo
      ureteroneocystostomy (redo-UNC) in pediatric vesicouretheral reflux (VUR)
      patients following open UNC and factors associated with redo-UNC. MATERIAL AND
      METHODS: Data on122 patients who underwent open UNC for VUR were analyzed in this
      retrospective case-control study. The patients were divided into a successful
      initial UNCgroup (UNC group, control) and an unsuccessful initial UNC group (redo
      UNC group, case).The following variables were analyzed: sex, age, dysfunctional
      voiding, laterality of VUR (unilateral or bilateral), VUR grade, etiology of VUR
      (primary or secondary), relative renal function on renal scintigraphy, and
      surgical technique. The use of the following procedures in the initial UNC was
      recorded: an endoscopic subureteric injection(ESI) and ureteral tapering.
      RESULTS: In our clinic, 122 patients (177 ureters),with an average age of 55.7 +/
      41.2 months (range, 1-18 years) underwent open UNC for VUR between November 2005
      and June 2014. Of these,67 (55%) had unilateral VUR, and 55(45%)  had bilateral
      VUR. There were 127 (71.8%) cases of grade 4-5 reflux. Postoperatively,
      hydronephrosis was noted in 19 (15.6%) patents. Ten (8.2%) patients underwent
      redo-UNC. In eight cases (6.5%), redo-UNC was performed because of ureterovesical
      (UV) junction obstruction.In the other two cases (1.7%), redo-UNC was due to high
      grade reflux. There were no statistically significant differences between the
      redo-UNC and UNC groups in any of the variables studied. CONCLUSION: Redo-UNC was
      required in 10 (8.2%) of cases after UNC. Age, sex, laterality of VUR, VUR grade,
      existence of primary or secondary VUR, relative renal function on renal
      scintigraphy, UNC technique, ESI procedure, and ureteral tapering were not risk
      factors for redo-UNC in our series.

PMID- 30120763
TI  - A Comparison of EORTC And CUETO Risk Tables in Terms of the Prediction of
      Recurrence and Progression in All Non-Muscle-Invasive Bladder Cancer Patients.
AB  - PURPOSE: To compare the prediction accuracy of the European Organization for
      Research and Treatment of Cancer (EORTC) and the Spanish Urology Association for
      Oncological Treatment (CUETO) risk tables in all non-muscle invasive bladder
      cancer patients. MATERIAL AND METHODS: Recurrence and progression-free survival
      of all patients were assessed according to the EORTC and the CUETO risk tables
      for each patient and the concordance index was used to indicate discriminative
      ability. Statistical analyses were performed, at 1 and 5 years, to the whole
      group and separately to those treated or not treated with BCG. RESULTS: The study
      included 400 patients. One-year BCG maintenance therapy was applied to 181
      patients (45.3%). The recurrence rate was higher than in CUETO, and similar to
      EORTC. The EORTC was determined to provide better discriminate than CUETO in the
      whole patient group and in those treated or not treated with BCG. The concordance
      index for these groups was 0.777, 0.705; 0.773, 0.669; and 0.823, 0.758,
      respectively . The progression rate was similar in this study to the rate defined
      in both risk tables. The discrimination power was similar in EORTC and CUETO for
      all the groups. The concordance index was 0.801, 0.881; 0.915, 0.930; and 0.832,
      0.806, respectively. CONCLUSIONS: The EORTC has more power than CUETO to
      discriminate each recurrence risk group and both risk tables can successfully
      discriminate progression risk groups in all patients.

PMID- 30120764
TI  - The Association of MYNN and TERC Gene Polymorphisms and Bladder Cancer in a
      Turkish Population.
AB  - PURPOSE: Researchers reported that, MYNN rs10936599 polymorphism is in strong or
      moderate linkage disequilibrium with SNPs within the 3q26.2 chromosomal region
      where is also includes the TERC gene. In addition, it has been reported that MYNN
      rs10936599 had a strong cumulative association with bladder cancer risk, and TERC
      gene suppresses cell growth in bladder cancer cell lines. In literature, there
      was not any study together evaluated of their effects of MYNN rs10936599 and TERC
      rs2293607 polymorphisms on BC risk. Therefore, we aimed to determine whether
      polymorphisms of MYNN rs10936599 and TERC rs2293607 play any role for bladder
      cancer in a Turkish population in this study. MATERIALS AND METHODS: In this case
      control study, 70 patients and 150 controls were investigated. Genotyping
      analysis was performed by polymerase chain reaction, restriction fragment length
      polymorphism and DNA sequencing techniques. RESULTS: Genotype distribution among
      both groups for MYNN rs10936599 SNP was significant different (p = .001); in
      spite of there was no difference in genotype distribution for TERC rs2293607 SNP.
      In addition, patients with CT genotype and CT+TT genotype combination of MYNN SNP
      have a decreased risk for bladder cancer. Two times increased risk ratio on
      development of bladder cancer was obtained for CC genotype of the SNP (p = .001).
      Besides, it has been found that genotype combination of GG+AG/CC versus AA/CC
      genotypes (TERC/MYNN) shown stronger correlation. Even, we obtained that
      statistically significant relationship of the C-G haplotypes of two polymorphisms
      on bladder cancer risk (p = .0001). CONCLUSION: At the end of the study, we
      suggested that, there may an association between a combination of MYNN rs10936599
      and TERC rs2293607 polymorphisms and development of bladder cancer in Turkish
      population.

PMID- 30120765
TI  - Two-stage laparoscopic repair of two-level ureteral strictures: our experience of
      8 patients.
AB  - PURPOSE: To evaluate the feasibility and effectiveness of two-stage laparoscopic
      repair for two-level ureteral strictures. MATERIALS AND METHODS: From October
      2010 to January 2017, 8 patients with two-level ureteral strictures, which were
      located in upper and lower ureter, received two-stage laparoscopic repair in our
      institution. Laparoscopic ureteroureterostomy was conducted for the upper
      ureteral strictures in first stage and 8 weeks later laparoscopic ureterovesical
      reimplantation was performed for lower stricture after the patency of upper
      lesion was confirmed by antegrade ureteropyelography. The kidney was drained by a
      nephrostomy tube during the interval period of two operations. RESULTS: All the
      operations were performed successfully without intraoperative complications
      except one patient converted to open surgery during second-stage operation. For
      first-stage surgery, mean operating time was 120.88 +/- 16.88 min, mean blood
      loss was 89.38 +/- 13.74 mL, and mean duration of postoperative hospitalization
      was 3.63 +/- 0.74 days. While in second-stage surgery, mean operating time took
      125.25 +/- 17.00 min, mean blood loss was 65.63 +/- 10.16 mL, and mean duration
      of postoperative hospitalization was 3.62 +/- 1.41 days.. On ureteropyelography
      10 weeks after second-stage surgery, the contrast medium flowed from kidney down
      into bladder unrestrictedly and the patency of entire ureter was restored in all
      patients. During the follow-up, one female was observed kidney atrophy with
      ureteral calculus formed on the lesion side, and was successfully treated by
      ureteroscopic lithotripsy. No sign of stricture recurrence was found on other
      patients. CONCLUSIONS: Two-stage laparoscopic repair is a feasible and effective
      treatment for two-level ureteral strictures. But its indication is relatively
      narrow and confined to ureteral strictures located in two sites with sufficient
      interval distance and minor stricture length.

PMID- 30120766
TI  - Comparison of Retrograde Intrarenal Surgery and Percutaneous Nephrolithotomy
      Methods For Management of Big- Sized Kidney Stones(? 4 cm): Single Center
      Retrospective Study.
AB  - PURPOSE: Management of ? 4 cm sized kidney stone is a rarely seen problem in
      urology. Few studies are present about this issue. Percutaneous
      nephrolithotomy(PNL), Retrograde Intrarenal Surgery(RIRS) and open surgery are
      the methods used in stone management. In our study we aimed to compare RIRS and
      PNL in the management of  ? 4 cm sized kidney stones. MATERIALS AND METHODS:  
      Among patients who had undergone RIRS and PNL in D?skap? Y?ld?r?m Beyaz?t
      Training and Research Hospital, 94 patients who had ? 4 cm sized kidney stones
      were included our study. The demographic, intraoperative and postoperative data
      of these patients and complications were evaluated retrospectively. RESULTS: 94
      patients (67 PNL, 27 RIRS) were in the study. Stone laterality, urinary anomaly
      and gender were similar in two groups.(Group PNL(P) and Group RIRS(R))  Stone
      number were 2.55+/-1.44 and 2.78+/-1.42 in Group P and R, respectively. Stone
      size were 47.06+/-7.02 and 46.41+/-6.00 mm. in Group P and R, respectively. The
      differences between two groups were not statistically significant.(p>.05) In
      Group P scopy time, hospital stay and stone free rate were higher and operation
      time was lower than  Group R. And the difference was statistically
      significant.(p<.05)Conclusions: As a result, PNL is an effective method and
      operation time is lower than RIRS. Also a second operation for JJ stent taking is
      lower in PNL . RIRS is a safe method. RIRS has less complications and
      hospitalization time.  They are feasible in treatment of ? 4 cm sized kidney
      stones.

PMID- 30120767
TI  - Association of macrophage inhibitory factor -173 gene polymorphism with
      biological behavior of prostate cancer.
AB  - PURPOSE: Chronic inflammation is an important factor in the etiology of prostate
      cancer. Macrophage migration inhibitory factor (MIF) plays an important
      regulatory role in inflammatory responses. The aim of this study was to
      investigate the potential association between MIF-173 G/C polymorphism, and both
      biological behavior and incidence of prostate cancer. MATERIALS AND METHODS:
      Analysis of polymorphic variants for MIF was performed using the polymerase chain
      reaction-restriction fragment length polymorphism (PCR-RFLP) method in 128
      subjects with prostate cancer and 135 controls. RESULTS: The frequency of MIF-173
      *C allele was significantly (OR = 2.18, 95% CI = 1.32-3.61) higher in patients
      with prostate cancer (19.5%) than in healthy individuals (10%).Prostate cancer
      patients with Gleason scores?7 had higher frequency of MIF-173 *C allele than
      Gleason scores<7 (86.1% vs. 27.1%, P = 0.003, OR = 3.18, 95% CI = 1.46-6.95). The
      frequency of MIF-173 *C allele was significantly different in patients with T1,
      T2 and ?T3 clinical stages of prostate cancer (15.2% vs. 42.6% and 47.8%, P =
      0.003). CONCLUSION: Our data suggest that MIF-173 polymorphisms may be associated
      with a higher incidence of prostate cancer compared to controls. We believe that
      MIF-173 GC+CC genotype can be used as a predictive factor for aggressive behavior
      of prostate cancer including pathological stage and Gleason scores as well as
      metastatic event.

PMID- 30120768
TI  - Evaluation of renal excretion and pharmacokinetics of furosemide in rats after
      acute exposure to high altitude at 4300 m.
AB  - With studies indicative of altered renal excretion under high altitude-induced
      hypobaric hypoxia, the consideration of better therapeutic approaches has long
      been the aim of research on the management of high altitude related illness. The
      pharmacokinetics of drugs such as furosemide might be altered under hypoxic
      conditions, making it essential to establish different dose-regimens to maintain
      therapeutic efficacy or to avoid toxic side effects at high altitude.
      Simultaneously, drug-drug interactions (DDIs) mediated by OAT1 occur at high
      altitude, severely affecting furosemide pharmacokinetics. This study investigated
      the influence of acute exposure to high altitude at 4300 m on the renal excretion
      of furosemide in rats. Significant changes in physiological parameters and kidney
      histopathology were found after acute high altitude exposure. Compared with low
      altitude, the pharmacokinetics of furosemide and the expression level of OAT1 in
      kidney were significantly changed after rapid ascent to high altitude.
      Additionally, the down-regulated OAT1 expression further sustained the potential
      mechanism for the decreased renal excretion of furosemide, resulting in extended
      residence of the drug in the human body. The elevation of AUC, Cmax , MRT, t1/2
      of furosemide, and decreased CL at high altitude further reinforced the current
      findings. Moreover, the absorption of furosemide was markedly increased and renal
      excretion significantly declined after co-administration of captopril, resulting
      in local drug interaction at high altitude. In conclusion, acute exposure to high
      altitude may significantly affect the renal excretion of furosemide and the
      pharmacokinetic parameters of furosemide were altered after co-administration of
      captopril, which may then impact the conventional therapeutic dosage.

PMID- 30120769
TI  - Quantification of in vivo gastric fluid volume in Bama miniature pigs in fasted
      state.
AB  - Although the study of bioequivalence waivers in humans is already well
      established, their application and translation into animals, which are
      complicated by differences in physiology, have only recently become subjects of
      interest. The main purpose of this paper is to quantify the liquid volume
      affecting drug dissolution in pig stomachs. We used magnetic resonance imaging
      (MRI) to scan 18 Bama miniature pigs weighing 15, 30 or 50 kg. Amira 6.0.1
      software was used for 3D image processing. We found that the gastric fluid volume
      had a linear relationship with the weight of pig (R2  = 0.9935) over this weight
      range. The pig weight, therefore, could be used as a surrogate for the fasted
      gastric fluid volume. After combining data of gastric fluid secretion and
      drinking water volumes, our results could be used as a reference for the
      evaluation of oral drug absorption in pigs.

PMID- 30120770
TI  - Estimating the impact of an organised screening programme on cervical cancer
      incidence: A 26-year study from northern Italy.
AB  - The impact of the organised cervical cancer (CC) screening programmes implemented
      in Europe since the 1990s has been insufficiently evaluated. We investigated the
      changes in CC incidence following the introduction of a screening programme in
      the Emilia-Romagna Region (northern Italy). The study period was 1988-2013. The
      programme, targeting women aged 25-64 years (1,219,000 in 2018), started in 1998.
      The annual incidence rates that would be expected in 1998-2013 in the absence of
      screening were estimated, first, by analysing the annual rates in 1988-1997 with
      a log-linear model and, second, by analysing the annual rates in 1988-2013 with
      an age-period model in which the period effect was enforced to be linear.
      Cervical adenocarcinoma incidence trend over the entire period was used to
      validate both estimates. Observed annual rates were compared to the two series of
      expected ones with the incidence rate ratio (IRR). Incidence remained stable
      during 1988-1997, peaked in 1998 and then decreased until 2007, when it
      stabilised. The two series of expected rates were virtually coincident and their
      trends roughly paralleled the stable adenocarcinoma incidence trend. After 2007,
      the median IRR was 0.60 (95% confidence interval, 0.45-0.81) based on the log
      linear model and 0.58 (95% confidence interval, 0.34-0.97) based on the age
      period model. Thirty-six to seventy-five CC cases were prevented annually for an
      average annual frequency of 6.5 per 100,000 women in the target population. In
      summary, consistent circumstantial evidences were obtained that the organised
      screening programme brought about a 40% reduction in annual CC incidence after 10
      years.

PMID- 30120771
TI  - Condition analysis of the Brazilian sharpnose shark Rhizoprionodon lalandii:
      evidence of maternal investment for initial post-natal life.
AB  - The present study analysed the condition factor (K) and the hepato-somatic index
      (IH ) of the Brazilian sharpnose shark Rhizoprionodon lalandii during its entire
      life cycle. Discontinuity of liver growth was observed after sexual maturity.
      High condition values were recorded in the length classes of 300-350 mm
      (neonates), when the livers represented about 8% of total mass, decreasing until
      the length classes of 400-450 mm and 450-500 mm in females and males,
      respectively. Seasonal analysis exhibited low IH values in the summer, while for
      K, low values were in spring, indicating greater investment for body growth
      during spring and for gonad maturation in summer. Such findings indicate that
      this small coastal shark species accumulates reserve substances in the liver that
      will be used during reproduction. The decline in IH values in juveniles suggests
      that reserves provisioned by the mother to the neonate liver can be used in the
      first months of life. This article is protected by copyright. All rights
      reserved.

PMID- 30120772
TI  - Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A
      pooled analysis of 3146 patients from phase 3 studies.
AB  - BACKGROUND: Evolocumab significantly lowers low-density lipoprotein cholesterol
      (LDL-C) when dosed 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM)
      subcutaneously. HYPOTHESIS: LDL-C changes are comparable among different patient
      subgroups in a pooled analysis of data from phase 3 trials. METHODS: A total of
      3146 patients received >=1 dose of evolocumab or control in four 12-week phase 3
      studies. Percent change from baseline in LDL-C for evolocumab 140 mg Q2W or 420
      mg QM vs control was reported as the average of week 10 and 12 values.
      Quantitative and qualitative interactions between treatment group and subgroup by
      dose regimen were tested. RESULTS: In the pooled analysis, treatment differences
      vs placebo or ezetimibe were similar for both 140 mg Q2W and 420 mg QM doses
      across ages (<65 years, >=65 years); gender; race (Asian, black, white, other);
      ethnicity (Hispanic, non-Hispanic); region (Europe, North America, Asia Pacific);
      glucose tolerance status (type 2 diabetes mellitus, metabolic syndrome, neither);
      National Cholesterol Education Program risk categories (high, moderately high,
      moderate, low); and European Society of Cardiology/European Atherosclerosis
      Society risk categories (very high, high, moderate, or low). Certain low
      magnitude variations in LDL-C lowering among subgroups led to significant
      quantitative interaction P values that, when tested by qualitative interaction,
      were not significant. The incidences of adverse events were similar across groups
      treated with each evolocumab dosing regimen or control. CONCLUSIONS: Consistent
      reductions in LDL-C were observed in the evolocumab group regardless of
      demographic and disease characteristics.

PMID- 30120773
TI  - The relationship between alkylamide compound content and pungency intensity of
      Zanthoxylum bungeanum based on sensory evaluation and ultra-performance liquid
      chromatography-mass spectrometry/ mass spectrometry (UPLC-MS/MS) analysis.
AB  - BACKGROUND: Zanthoxylum bungeanum originating in different places varies in
      alkylamide content and pungency intensity. RESULTS: The pungency intensity of 19
      Zanthoxylum bungeanum samples was first determined with Scoville pungency units
      (SPUs). The SPUs were found to range from 3.80E + 04 to 5.40E + 05. The chemical
      compositions and contents were measured next, using the ultra-performance liquid
      chromatography-mass spectrometry/ mass spectrometry (UPLC-MS/MS) method. The
      total alkylamide content ranged from 9.83 +/- 0.15 to 89.98 +/- 1.35 g kg-1 .
      Hydroxy-epsilon-sanshool, hydroxy-alpha-sanshool, hydroxy-beta-sanshool, hydroxy
      gamma-sanshool, bungeanool, and isobungeanool were found to be the key pungent
      compounds, ranging in proportion from 92.65% to 97.69%. The relationship between
      alkymide compound content and pungency intensity was also analyzed by ridge
      regression, and it was found that the beta values of independent variables were
      stable when k was more than 0.6. The regression coefficients of hydroxy-epsilon
      sanshool, hydroxy-alpha-sanshool, hydroxy-beta-sanshool, hydroxy-gamma-sanshool,
      bungeanool, isobungeanool, and other alkylamides were 0.105, 0.177, 0.386, 
      0.166, -0.006, 0.005, and -0.018, respectively. CONCLUSION: Hydroxy- sanshool
      compounds were important in determinant the pungency intensity of Z. bungeanum.
      Knowledge of the relationship between alkymide compound content and pungency
      intensity will assist in the creation of new methods to determine pungency
      intensity and provide a scientific basis for flavor design, development of
      pungent food products, and consumer choice evaluations. (c) 2018 Society of
      Chemical Industry.

PMID- 30120774
TI  - Getting to Long-Term Effectiveness and Safety of Attention-deficit Hyperactivity
      Disorder Medications.
AB  - Attention-deficit hyperactivity disorder (ADHD) medication use has dramatically
      increased in youth worldwide. Recent prevalence data in some European countries
      show expanded use with one country now matching US usage. Still, substantial
      geographic differences by country remain regarding the extent to which children
      receive ADHD medications. These geographic differences by country raise research
      questions about which country's prevalence data represents appropriate medication
      use. We urgently need country level studies to contribute to our understanding of
      an appropriate prevalence of ADHD medication use.

PMID- 30120775
TI  - Randomized controlled trial of continuous Doppler versus intermittent fetoscope
      fetal heart rate monitoring in a low-resource setting.
AB  - OBJECTIVE: To compare the frequency of abnormal fetal heart rate (FHR) detection
      between continuous Doppler and intermittent fetoscope monitoring. METHOD: A
      randomized controlled open-label trial was conducted between February 1, 2016,
      and January 31, 2017, at Haydom Lutheran hospital, Tanzania. Women in active
      labor with singleton pregnancies and normal FHR at admission were randomly
      allocated in a 1:1 ratio to receive either continuous or intermittent FHR
      monitoring. The primary outcome was abnormal FHR detection. RESULTS: 2652 women
      were enrolled; 1340 received continuous monitoring and 1312 received intermittent
      monitoring. Continuous FHR monitoring detected abnormal FHR in 108 (8.1%)
      participants versus 40 (3.0%) participants in the intermittent monitoring group
      (risk ratio [RR] 2.64, 95% confidence interval [CI] 1.8-3.7; P<0.001). The
      increased detection rate in the continuous versus intermittent monitoring group
      was associated with an increase in rate of subsequent intrauterine resuscitations
      (89 [6.6%] vs 42 [3.2%]; RR 2.07, 95% CI 1.4-2.9; P<0.001). In total, 92 (3.5%)
      infants had adverse perinatal outcomes, with no significant differences between
      groups. CONCLUSION: Continuous FHR monitoring increased identification of
      abnormal FHR and subsequent intrauterine resuscitations. ClinicalTrials.gov:
      NCT02790814.

PMID- 30120778
TI  - Defining Regional Differences in Drug-Induced Stevens-Johnson Syndrome/Toxic
      Epidermal Necrolysis: A Tool to Improve Drug Safety?

PMID- 30120777
TI  - Interaction between the signaling molecules hydrogen sulfide and hydrogen
      peroxide and their role in vacuolar H+ -ATPase regulation in cadmium-stressed
      cucumber roots.
AB  - Vacuolar H+ -ATPase (V-ATPase; EC 3.6.3.14) is the main enzyme responsible for
      generating a proton gradient across the tonoplast. Under cadmium (Cd) stress
      conditions, V-ATPase activity is inhibited. In the present work, hydrogen sulfide
      (H2 S) and hydrogen peroxide (H2 O2 ) cross-talk was analyzed in cucumber
      (Cucumis sativus L.) seedlings exposed to Cd to explain the role of both
      signaling molecules in the control of V-ATPase. V-ATPase activity and gene
      expression as well as H2 S and H2 O2 content and endogenous production were
      determined in roots of plants treated with 100 MUM CdCl2 and different inhibitors
      or scavengers. It was found that H2 S donor improved photosynthetic parameters in
      Cd-stressed cucumber seedlings. Cd-induced stimulation of H2 S level was
      correlated with the increased activities of the H2 S-generating desulfhydrases.
      Increased H2 O2 and lowered H2 S contents in roots were able to reduce V-ATPase
      activities similar to Cd. H2 O2 and H2 S-induced modulations in V-ATPase
      activities were not closely related to the transcript level of encoding genes,
      suggesting posttranslational modifications of enzyme protein. On the other hand,
      exogenous H2 O2 raised H2 S content in root tissues independently from the
      desulfhydrase activity. Although treatment of control plants with H2 S
      significantly stimulated NADPH oxidase activity and gene expression, H2 S did not
      affect H2 O2 accumulation in roots exposed to Cd. The results suggest the
      existence of two pathways of H2 S generation in Cd-stressed cucumber roots. One
      involves desulfhydrase activity, as was previously demonstrated in different
      plant species. The other, the desulfhydrase-independent pathway induced by H2 O2
      /NADPH oxidase, may protect V-ATPase from inhibition by Cd.

PMID- 30120776
TI  - Unique predictive power of other-rated personality: An 18-year longitudinal
      study.
AB  - OBJECTIVE: What is gained by having others report on one's personality? Research
      on adult samples has suggested that informant reports are especially informative
      regarding traits that are highly visible and evaluative (i.e., socially
      desirable/undesirable instead of neutral), such as Openness, Conscientiousness,
      and Agreeableness. This 18-year longitudinal study aims to demonstrate the unique
      predictive power of other-rated personality in adolescence, using life outcomes
      and personality in adulthood as trait criteria. METHOD: We examined the unique
      predictive power of self- and other-rated Big Five personality traits at age 12
      and 17 on self-rated life outcomes and personality at age 29 (e.g., educational
      achievement, work income, depression, moral transgressions, and relationship
      satisfaction). Participants were 186 German adolescents (53% boys), their parents
      and friends at age 12, and their mothers and fathers at age 17. RESULTS: Other
      ratings showed unique predictive power beyond self-ratings for all Big Five
      traits, with the most consistent results for Openness, Conscientiousness, and
      Agreeableness. CONCLUSIONS: Results demonstrate the added value of including
      other-reports on adolescent personality when predicting future life outcomes and
      personality, especially for highly visible and evaluative traits. The present
      study sheds light on the predictive power of self- versus other-rated personality
      and personality-outcome associations.

PMID- 30120779
TI  - Quantitative determination of levonorgestrel in beagle dog plasma after vaginal
      administration of intravaginal ring by high-performance liquid chromatography
      tandem mass spectrometry.
AB  - A specific and sensitive high-performance liquid chromatography-tandem mass
      spectrometry method that could be used to determine the concentration of
      levonorgestrel (LNG) in beagle dog plasma was developed. Specifically,
      terfenadine was used as the internal standard (IS). The separation was achieved
      on a Kinetex-C18 110A column (3 * 30 mm i.d., 2.6 um, Phenomenex) and a gradient
      mobile phase consists of methanol (0.1% formic acid) and water (0.1% formic acid)
      was used. The flow rate was 0.8 mL/min and the injection volume was 10 MUL. The
      detection was performed on a triple-quadruple tandem mass spectrometer by
      multiple reaction monitoring mode via electrospray ionization. Quantitative
      analysis was carried out at m/z 313.0 -> 108.9 and m/z 472.6 -> 436.2 for LNG and
      IS respectively. This method demonstrated the linearity of LNG over a
      concentration range of 0.5-50 ng/mL with a coefficient correlation (r) of 0.9973.
      The lower limit of quantification was 0.5 ng/mL. The intra- and inter-assay
      precisions were 2.9 and 11.2%, with an accuracy range from 94.8 to 108.4%. The
      stability data indicated that sample preparation and storage process had little
      effect on the concentration of LNG QC sample. The validated method was
      successfully applied to study the pharmacokinetics of LNG in beagle dog after
      vaginal administration of intravaginal ring.

PMID- 30120780
TI  - Motivation alters implicit temporal attention through sustained and transient
      mechanisms: A behavioral and pupillometric study.
AB  - Temporal expectations aid performance by allowing the optimization of attentional
      readiness at moment of highest target probability. Reward enhances cognitive
      performance through its action on preparatory and reactive attentional processes.
      To elucidate how motivation interacts with mechanisms of implicit temporal
      attention, we studied healthy young adult participants (N = 73) performing a
      sustained attention task with simultaneous pupillometric recording, under
      different reward conditions (baseline: 0 c; reward: 10 c/fast response). Target
      timing was temporally unpredictable (variable foreperiod: 2-10 s, uniformly
      distributed), in which case implicitly formed timing expectations. Trials were
      binned according to current foreperiod (FPn ; short: 2-6 s; long: 6-10 s) and
      preceding foreperiod (FPn-1 ; short: 2-6 s; long: 6-10 s). Overall, performance
      data showed the expected temporal attention effects, with slower responses after
      shorter FPn s, particularly when they followed longer FPn-1 s. Moreover, these
      temporal effects were significantly reduced in the reward condition. While
      performance improved in all trial types, the largest benefit appeared in trials
      that were normally most disadvantaged by invalid temporal expectation.
      Furthermore, reward motivation was accompanied by an increase in sustained
      (prestimulus) and transient (poststimulus response) pupil diameter. The latter
      effect was particularly evident following short FPn s. The current findings
      suggest that reward motivation can improve overall attentional performance and
      reduce implicit temporal bias, both through preparatory and reactive attentional
      mechanisms.

PMID- 30120781
TI  - A rapid and reliable assay to determine flumequine, marbofloxacin, difloxacin,
      and sarafloxacin in commonly consumed meat by micellar liquid chromatography.
AB  - BACKGROUND: Micellar liquid chromatography - fluorescence detection was used to
      determine the antibiotics flumequine, marbofloxacin, difloxacin, and sarafloxacin
      in porcine, bovine, poultry, ovine, caprine, rabbit, and equine meat, to verify
      compliance with EU Regulation 37/2010 with regard to the occurrence of veterinary
      drugs in food. RESULTS: The analytes were isolated from the matrix by
      ultrasonication-assisted leaching in a micellar solution, and the supernatant was
      filtered and directly injected. The fluoroquinolones were resolved in < 19 min
      using a C18 column, with an isocratic mobile phase of 0.05 mol L-1 sodium dodecyl
      sulfate - 8% 1-butanol - 0.5% triethylamine buffered at pH 3. The limits of
      quantification (0.01-0.05 mg kg-1 ) were below the maximum residue limits (0.15
      0.4 mg kg-1 ). The method was validated by EU Commission Decision 2002/657/EC
      guidelines. CONCLUSION: The method shows practical advantages such as simplicity,
      low cost, eco-friendliness, safety, and applicability for routine analysis, and
      is useful for surveillance programs. (c) 2018 Society of Chemical Industry.

PMID- 30120783
TI  - Industry Actions to Address Quality Issues for Dietary Supplements, Botanicals,
      and Other Natural Products.
AB  - The concept of "dietary supplements" is either a blessing for those focused on
      healthy lifestyles and personal management thereof or a crisis fraught with snake
      oil and drug analogs that are insidiously poisoning the gullible. Lost in this
      chatter is the role the ethical, and customer-focused industry takes to drive
      self-directing/self-governing initiatives to demonstrate unequivocally their
      position as responsible corporate citizens, meeting the needs of the ever-growing
      body of wellness-seekers.

PMID- 30120782
TI  - Determination of glucosamine and monitoring of its mutarotation by hydrophilic
      interaction liquid chromatography with evaporative light scattering detector.
AB  - Saccharides and their derivatives are typical polar analytes without a suitable
      UV-chromophore that are nowadays analyzed by HPLC (high-performance liquid
      chromatography) under HILIC (hydrophilic interaction liquid chromatography) mode.
      Usually an evaporative light scattering detector (ELSD) is utilized which,
      however, gives a nonlinear response. A procedure to overcome the problem of
      mutarotating (time-varying) analytes recorded with such a nonlinear response
      detector is described. The procedure was applied for determination of glucosamine
      in two commercially available pharmaceutical formulations containing the common
      inorganic ions that the detector gives a response to. Under optimized conditions,
      both the anomers of glucosamine were separated and could be determined
      separately. Owing to the short retention time of the analyte (a run time <4 min)
      and relatively slow kinetics of the anomeric conversion (equilibration time 2.5
      h), mutarotation could be monitored and corresponding rate constants calculated.

PMID- 30120784
TI  - Clinical and echocardiographic parameters as risk factors for atrial fibrillation
      in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common complication in patients with
      hypertrophic cardiomyopathy (HCM) and may contribute to high cardiovascular
      morbidity and mortality. Therefore, it is important to assess parameters
      associated with AF in HCM patients. HYPOTHESIS: The aim of the study was to
      evaluate AF prevalence in patients with HCM and to investigate risk factors for
      AF. METHODS: Five hundred and forty-six HCM patients aged below 65 were included
      into analysis. Clinical and echocardiographic parameters were analyzed. RESULTS:
      In 141 patients (25.8%) AF episodes were recorded. The following factors were
      identified as risk factors for AF in patients with HCM: age >= 45 years (OR 2.38,
      CI 1.40-4.05, P = 0.001), past history of presyncope or syncope (OR 2.25, CI 1.35
      3.74, P = 0.002), non-sustained ventricular tachycardia (nsVT) (OR 2.70, CI 1.60
      4.57, P < 0.001), left atrium diameter during first assessment (OR 1.065, CI 1.03
      1.11, P = 0.001), left atrium diameter at the last assessment before AF
      occurrence (OR 1.10, CI 1.06-1.14, P < 0.001) and left ventricular ejection
      fraction at the last assessment before AF occurrence (CI 0.96, CI 0.94-0.98, P =
      0.001). CONCLUSIONS: We confirm that AF is a common complication for patients
      with HCM. Identification of patients with high risk for AF and implementation of
      preventive strategies may reduce AF occurrence and its complications.

PMID- 30120785
TI  - Simultaneous TLC-densitometric determination of tamoxifen citrate and
      medroxyprogesterone acetate and UV-degradation kinetic study of
      medroxyprogesterone acetate.
AB  - Coadministration of tamoxifen citrate (TMC) and medroxyprogesterone acetate (MPA)
      is preferred to increase the response rate and the percentage recovery in
      patients with endometrial carcinoma. Administration of TMC and MPA and their
      combination affects estrogen and progestin receptor concentrations in advanced
      endometrium carcinoma by affecting 17beta-hydroxyl steroid dehydrogenase activity
      and serum hormone concentrations. A sensitive, accurate and robust thin-layer
      chromatography method has been established for simultaneous analysis of TMC and
      MPA. Method development was carried out on silica gel F254 using butanol-acetic
      acid-water (6:0.5:0.5, v/v/v) as mobile phase. Densitometric scanning was carried
      out at 241 nm for simultaneous detection of TMC and MPA. Retardation factor (Rf )
      values for TMC and MPA were 0.21 and 0.85, respectively. The method was validated
      according to ICH guidelines. Regression plots revealed linear relationships in
      the concentration range of 50-500 and 25-250 ng/band for TMC and MPA,
      successively. Accuracy was >=99.60 and 98.72% for TMC and MPA, respectively.
      Forced degradation studies using UV photodegradation was applied on MPA after
      exposure to UV light for different times and applying a kinetic study for
      calculating the degradation rate constant (k) and half-life time (t1/2 ).

PMID- 30120786
TI  - Factors impacting on the action of glucocorticoids in patients receiving
      glucocorticoid therapy.
AB  - Glucocorticoids (GCs) are steroid hormones, which are essential for life. They
      are secreted by the adrenal cortex under the control of the hypothalamic
      pituitary-adrenal (HPA) axis. Glucocorticoids are essential for the normal
      function of most organ systems and, in both, excess and deficiency can lead to
      significant adverse consequences. Adrenal insufficiency (AI) is a rare, life
      threatening disorder characterized by insufficient production of corticosteroid
      hormones. Primary AI is defined by the inability of the adrenal cortex to produce
      sufficient amounts of glucocorticoids and/or mineralocorticoids despite normal or
      increased adrenocorticotropin hormone (ACTH). Secondary AI is adrenal
      hypofunction due to insufficient amount of ACTH produced by the pituitary gland.
      Conventional treatment of both primary and secondary adrenal insufficiencies
      involves lifelong glucocorticoid replacement therapy. The role of cortisol
      deficiency and the impact of hydrocortisone replacement on morbidity and
      mortality in this patient group are under increasing scrutiny. Established
      glucocorticoid replacement regimens do not completely mirror endogenous hormonal
      production, and their monitoring to ensure optimum therapy is hampered by the
      lack of reliable biomarkers of hormone sufficiency. A further confounding issue
      is the tissue-specific regulation of glucocorticoid through the two isozymes of
      11beta-hydroxysteroid dehydrogenase (11beta-HSD) with research focusing on the
      role of this prereceptor regulation in the development of adverse metabolic
      features in patients. This review defines the factors influencing glucocorticoid
      action in patients with adrenal insufficiency receiving glucocorticoid therapy.

PMID- 30120787
TI  - Two macamide extracts relieve physical fatigue by attenuating muscle damage in
      mice.
AB  - BACKGROUND: Macamides, the main active components contained in maca, have
      attracted increasing attention due to their various bioactivities. In this study,
      crude macamide extract (CME) and purified macamide extract (PME) were prepared by
      enzyme-assisted extraction and macroporous resin separation, and the anti-fatigue
      effects of CME and PME were evaluated in a forced swimming model. RESULTS: The
      composition analysis results revealed that both CME and PME mainly contain eight
      kinds of macamide. Based on the results of a weight-loaded forced swimming test,
      compared with a control group, CME and and PME groups could prolong exhaustive
      swimming time, increase levels of liver glycogen (LG) and muscle glycogen (MG),
      accelerate fatty acid oxidation in serum to provide energy, eliminate the
      accumulation of blood lactic acid (BLA) and blood urea nitrogen (BUN), and
      decrease the serum biomarkers for muscle damage, such as lactate dehydrogenase
      (LDH) and creatine kinase (CK). Histological analysis also indicated that CME and
      PME attenuated damage to skeletal muscle and the myocardium in mice during
      exercise. CONCLUSION: Two macamide extracts have a beneficial effect on relieving
      physical fatigue by attenuating the damage of skeletal muscle and myocardium
      during exercise, and a better effect was observed in the PME group. (c) 2018
      Society of Chemical Industry.

PMID- 30120788
TI  - A novel enzymatic method for the measurement of lactose in lactose-free products.
AB  - BACKGROUND: In recent years there has been a surge in the number of commercially
      available lactose-free variants of a wide variety of products. This presents an
      analytical challenge for the measurement of the residual lactose content in the
      presence of high levels of mono-, di-, and oligosaccharides. RESULTS: In the
      current work, we describe the development of a novel enzymatic low-lactose
      determination method termed LOLAC (low lactose), which is based on an optimized
      glucose removal pre-treatment step followed by a sequential enzymatic assay that
      measures residual glucose and lactose in a single cuvette. Sensitivity was
      improved over existing enzymatic lactose assays through the extension of the
      typical glucose detection biochemical pathway to amplify the signal response.
      Selectivity for lactose in the presence of structurally similar oligosaccharides
      was provided by using a beta-galactosidase with much improved selectivity over
      the analytical industry standards from Aspergillus oryzae and Escherichia coli
      (EcLacZ), coupled with a 'creep' calculation adjustment to account for any
      overestimation. The resulting enzymatic method was fully characterized in terms
      of its linear range (2.3-113 mg per 100 g), limit of detection (LOD) (0.13 mg per
      100 g), limit of quantification (LOQ) (0.44 mg per 100 g) and reproducibility (<=
      3.2% coefficient of variation (CV)). A range of commercially available lactose
      free samples were analyzed with spiking experiments and excellent recoveries were
      obtained. Lactose quantitation in lactose-free infant formula, a particularly
      challenging matrix, was carried out using the LOLAC method and the results
      compared favorably with those obtained from a United Kingdom Accreditation
      Service (UKAS) accredited laboratory employing quantitative high performance
      anion exchange chromatography - pulsed amperometric detection (HPAEC-PAD)
      analysis. CONCLUSION: The LOLAC assay is the first reported enzymatic method that
      accurately quantitates lactose in lactose-free samples. (c) 2018 The Authors.
      Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd
      on behalf of Society of Chemical Industry.

PMID- 30120789
TI  - Culturable epiphytic bacteria isolated from Teleogryllus occipitalus crickets
      metabolize insecticides.
AB  - The development of insecticide resistance is attributed to evolutionary changes
      in pest insect genomes, such as alteration of drug target sites, upregulation of
      degrading enzymes, and enhancement of drug excretion. Beyond these well-known
      mechanisms, symbiotic bacteria may confer insecticide resistance to host
      crickets. The current study was designed to screen all possible culturable
      bacterial groups found living in and on the bodies of Teleogryllus occipitalis
      crickets. We recovered 263 visible bacterial colonies and cultured them
      individually. After identifying the colonies based on morphology and phylogenetic
      analysis, we shortlisted 55 bacterial strains belonging to 28 genera. Of these 55
      bacterial strains, 18 degraded at least 50% of the original amount of 400 mg/L
      chlorpyrifos (CP) after 24 hr of coculture. Six of these strains degraded more
      than 70% of the original amount of 400 mg/L CP. Three strains had antagonistic
      effects on Bacillus thuringiensis growth. Additionally, the ability of the
      isolates to degrade glyphosate, phoxim, and esfenvalerate was assessed. We also
      detected extracellular hydrolase enzyme activities in these isolates. We propose
      that epiphytic bacterial strains play multiple roles in cricket biology, one of
      which contributes to chemical and biological pesticide resistance.

PMID- 30120791
TI  - Selective differentiation during the colonization and establishment of a newly
      invasive species.
AB  - The potential for rapid evolution in invasive species makes them useful for
      studying adaptive responses of populations to novel environments. However,
      phenotypic divergence during invasion is not necessarily due to selection, but
      may be a product of neutral processes resulting from population bottlenecks
      during colonization and range expansion. We investigated phenotypic adaptation
      during the establishment and range expansion of the invasive bunchgrass, slender
      false brome (Brachypodium sylvaticum; Poaceae). Utilizing a novel approach, we
      made robust comparisons of functional traits using genetic similarity based on
      unique alleles to determine the genetic probability of contribution from native
      source regions and integrated these probabilities into our QST -FST comparisons
      for 12 physiological and anatomical traits associated with drought stress in the
      introduced range. Our results indicate phenotypic divergence greater than neutral
      expectations in five traits between native and invasive populations, indicating
      selective divergence occurred during invasive species establishment. The results
      indicate that the majority of divergence in B. sylvaticum occurred after
      introduction to the novel environment, but prior to invasive range expansion.
      This study provides evidence for adaptive genetic differentiation during the
      establishment of an invasive species, while also describing a robust method for
      the detection of selective processes after species introduction to a novel
      environment.

PMID- 30120792
TI  - Eicosanoid mediation of immune responses at early bacterial infection stage and
      its inhibition by Photorhabdus temperata subsp. temperata, an entomopathogenic
      bacterium.
AB  - An entomopathogenic bacterium Photorhabdus temperata subsp. temperata (Ptt)
      infects insect hemocoel by the vectoring activity of its symbiotic nematode,
      Heterorhabditis megidis. The bacterium induces host immunosuppression by
      inhibiting eicosanoid biosynthesis. This study investigated the role of
      eicosanoids in immune responses of the beet armyworm, Spodoptera exigua, in the
      early bacterial infection stage (first 3 hr postinfection [PI]). After infection
      with the nonpathogenic Escherichia coli (Ec), the bacterium maintained its
      population for the first 3 hr PI, then rapidly decreased in numbers. During the 3
      hr PI of Ptt, this pathogenic bacterium also did not show any significant change
      in bacterial population. However, Ptt rapidly increased its population size after
      the initial lag phase, inducing fatal septicemia. This study further analyzed
      cellular and humoral immune responses of the beet armyworm during the initial 3
      hr PI. During this early stage, challenge with Ec stimulated hemocyte-spreading
      behavior along with extensive F-actin growth. However, Ptt infection suppressed
      hemocyte spreading. Expression levels of three antimicrobial peptides (lysozyme,
      gloverin, and gallerimycin) were significantly inhibited during Ptt infection.
      Phospholipase A2 activity was significantly induced during the early infection
      stage of Ec, but not during Ptt infection. Addition of eicosanoid biosynthesis
      inhibitors significantly reversed the initial immunosuppression. These results
      suggest that, during the early infection stage, Ptt can shutdown eicosanoid
      biosynthesis which can prevent acute immune responses of host insects.

PMID- 30120790
TI  - Effect of fertilization and arbuscular mycorrhizal fungal inoculation on
      antioxidant profiles and activities in Fragaria ananassa fruit.
AB  - BACKGROUND: The main methods used to increase the yield and quality of strawberry
      fruit produced in acidic soils with low P availability include root colonization
      by arbuscular mycorrhizal (AM) fungi and adjusting the type of P supplementation
      by means of traditional (TF) or organic (OF) fertilization, and adjusting
      nutrient doses. In this study, the antioxidant properties of strawberry fruit
      were evaluated under different treatments of fertilization (TF or OF) and
      different doses of P supplied at planting (0, 50 or 100% of the agronomic
      recommendation) and in the presence or absence of AM fungus as a bioinoculant.
      RESULTS: Fruits without fertilization treatments and with TF presented with
      higher anthocyanin concentrations. In general, higher values were obtained
      without AM colonization. However, spectrophotometric tests showed the highest
      activity and concentration in the AM-inoculated treatments. It is likely that
      phenolic compounds other than anthocyanins are present in the extracts. These
      other compounds could not be identified by the method used but could be detected
      by the Folin-Ciocalteu method. CONCLUSION: This study provides information that
      allows for improvements in strawberry fruit quality by agronomic management, with
      a potential beneficial effect on the health of consumers. (c) 2018 Society of
      Chemical Industry.

PMID- 30120793
TI  - Sterols of the Toxic Marine Dinoflagellate, Pyrodinium bahamense.
AB  - Pyrodinium bahamense is a dinoflagellate of concern in subtropical and tropical
      coastal environments. To date, there is only a single published study on its
      fatty acids, but no published data on its sterol composition. Sterols, which are
      membrane-reinforcing lipids in eukaryotes, display a great diversity of
      structures in dinoflagellates, with some serving as chemotaxonomic markers. We
      have examined the sterol compositions of two isolates of P. bahamense from Indian
      River Lagoon and Tampa Bay, Florida, and have found both to produce three
      sterols: cholesterol, dinosterol, and 4alpha-methylgorgostanol. All three sterols
      are found in closely related, armored taxa.

PMID- 30120794
TI  - Monitoring of glutamate-induced excitotoxicity by mitochondrial oxygen
      consumption.
AB  - Dysfunction of mitochondrial activity is often associated with the onset and
      progress of neurodegenerative diseases. Membrane depolarization induced by Na+
      influx increases intracellular Ca2+ levels in neurons, which upregulates
      mitochondrial activity. However, overlimit of Na+ influx and its prolonged
      retention ultimately cause excitotoxicity leading to neuronal cell death. To
      return the membrane potential to the normal level, Na+ /K+ -ATPase exchanges
      intracellular Na+ with extracellular K+ by consuming a large amount of ATP. This
      is a reason why mitochondria are important for maintaining neurons. In addition,
      astrocytes are thought to be important for supporting neighboring neurons by
      acting as energy providers and eliminators of excessive neurotransmitters. In
      this study, we examined the meaning of changes in the mitochondrial oxygen
      consumption rate (OCR) in primary mouse neuronal populations. By varying the
      medium constituents and using channel modulators, we found that pyruvate rather
      than lactate supported OCR levels and conferred on neurons resistance to
      glutamate-mediated excitotoxicity. Under a pyruvate-restricted condition, our OCR
      monitoring could detect excitotoxicity induced by glutamate at only 10 MUM. The
      OCR monitoring also revealed the contribution of the N-methyl-D-aspartate
      receptor and Na+ /K+ -ATPase to the toxicity, which allowed evaluating
      spontaneous excitation. In addition, the OCR monitoring showed that astrocytes
      preferentially used glutamate, not glutamine, for a substrate of the
      tricarboxylic acid cycle. This mechanism may be coupled with astrocyte-dependent
      protection of neurons from glutamate-mediated excitotoxicity. These results
      suggest that OCR monitoring would provide a new powerful tool to analyze the
      mechanisms underlying neurotoxicity and protection against it.

PMID- 30120795
TI  - Discrimination of wild and domestic deer musk using isotope ratio mass
      spectrometry.
AB  - Musk is the dried secretion of the musk pod (sac) of adult male musk deer, and
      has been used as perfume and traditional medicine for thousands of years. Steroid
      was regarded as 1 of the most important active compounds in musk. In order to
      protect the wild musk deer, musk deer farming has been carried out in China,
      India, and Nepal. However, it is hard to differentiate the 2 origins of musk by
      morphological identification. No other method has been reported so far for the
      discrimination of wild and domestic deer musk. The establishment of a reliable
      discrimination method has become an urgent work. In the present study, 6 batches
      of wild deer musk and 14 batches of domestic deer musk were collected. Analysis
      of steroid components in musk was carried out with GC-MS/MS. Androgen, progestin,
      estrogen, and sterol were detected in those samples. Large diversity was observed
      in the concentrations of steroids in musk. No obvious difference could be
      observed in steroid concentrations between wild and domestic deer musk by
      principal component analysis and cluster analysis. Furthermore, the delta13 C
      values of steroids were determined by gas chromatography/combustion coupled with
      isotopic ratio mass spectrometry. There were significant differences (P < .01) in
      steroid delta13 C values between wild origin musk and domesticated origin musk.
      Isotopic ratio mass spectrometry can be used to discriminate wild and domestic
      deer musk.

PMID- 30120796
TI  - Investigating the time-lapsed effects of rigid cervical collars on the dimensions
      of the internal jugular vein.
AB  - Protocol advocates the use of rigid cervical collars (RCCs) in head trauma
      patients as they are at risk of concomitant cervical spine injury. Literature has
      shown RCCs to be a potential cause of venous outflow obstruction, changing
      internal jugular vein (IJV) cross-sectional area (CSA), and raising intracranial
      pressure (ICP). This study aims to investigate the effects of applying a RCC, for
      a period of four hours, on the dimensions of the IJV, in healthy participants.
      Seventeen participants (nine male, eight female) took part in this study.
      Circumference and CSAs of the IJV were measured bilaterally by a single observer
      using a GE LOGIQ e ultrasound system. Measurements were taken pre-RCC
      application, immediately after, every hour over four hours, and five minutes
      postcollar removal. The CSA of the IJV was 8.3 +/-6.0 mm2 pre-RCC application.
      The CSA of the IJV doubled (18.92 +/-10.55 mm2 ) after four hours and decreased
      back to 9.36 +/-6.8 mm2 five minutes postcollar removal. The circumference of the
      IJV was 17.29 +/-6.03 mm pre-RCC application, increasing to 20.34 +/-5.59 mm by
      the end of the fourth hour and returning to 16.14 +/-5.16 mm five minutes
      postcollar removal. Related-samples Friedman's ANOVA test showed statistically
      significant differences for both left and right CSAs and circumferences of the
      IJV measured across the four hours (P-value<0.05). Ultrasound assessment of CSA
      of the IJV may correlate with changes in ICP. Further studies may provide insight
      into the effects of collar design, and guide future trauma protocol to minimize
      intracranial pressure fluctuations. Clin. Anat., 2018. (c) 2018 Wiley
      Periodicals, Inc.

PMID- 30120798
TI  - Severe cytomegalovirus enterocolitis developing following daratumumab exposure in
      three patients with multiple myeloma.
AB  - OBJECTIVES: The risk of cytomegalovirus (CMV) reactivation in multiple myeloma
      (MM) patients treated with bortezomib-based induction regimens is increased
      following autologous stem cell transplantation (ASCT). There is paucity of data
      regarding the risk of CMV infections in MM patients who did not receive
      bortezomib and ASCT. METHODS: We herein report three cases of heavily pretreated
      MM patients, receiving daratumumab-containing combination regimens, in whom ASCT
      had been performed long ago and who recently developed severe CMV-related
      gastrointestinal disease. RESULTS: All the three patients had a prolonged CMV
      disease course requiring a long-term antiviral treatment. All the patients
      suffered from CMV colitis. One patient had concurrent CMV duodenitis and another
      patient had a concurrent CMV retinitis. CONCLUSION: Novel myeloma treatments
      prolong patient survival and more patients with profound immunosuppression
      following multiple lines of therapies are seen in clinical practice. These
      patients may present with opportunistic infections that were rare in the past.
      Our findings suggest a possible association between daratumumab therapy (in
      combination with other immunosuppressive therapies) and severe CMV
      gastrointestinal disease. A longer follow-up is needed to explore long-term side
      effects of novel agents like daratumumab in newly diagnosed as well as heavily
      pretreated MM patients.

PMID- 30120797
TI  - The evidential statistical paradigm in genetics.
AB  - Concerns over reproducibility in research has reinvigorated the discourse on P
      values as measures of statistical evidence. In a position statement by the
      American Statistical Association board of directors, they warn of P-value misuse
      and refer to the availability of alternatives. Despite the common practice of
      comparing P-values across different hypothesis tests in genetics, it is well
      appreciated that P-values must be interpreted alongside the sample size and
      experimental design used for their computation. Here, we discuss the evidential
      statistical paradigm (EP), an alternative to Bayesian and Frequentist paradigms,
      that has been implemented in human genetics studies. Using applications in Cystic
      Fibrosis genetic association analyses, and describing recent theoretical
      developments, we review how to measure statistical evidence using the EP in the
      presence of covariates, model misspecification, and for composite hypotheses.
      Novel graphical displays are presented, and software for their computation is
      highlighted. The implications of multiple hypothesis testing for the EP are
      delineated in the analyses, demonstrating a view more consistent with scientific
      reasoning; the EP provides a theoretical justification for replication that is a
      requirement in genetic association studies. As genetic studies grow in size and
      complexity, a fresh look at measures of statistical evidence that are sensible
      amid the analysis of big data are required.

PMID- 30120799
TI  - Molybdenum- and tungsten-containing formate dehydrogenases and formylmethanofuran
      dehydrogenases: Structure, mechanism, and cofactor insertion.
AB  - An overview is provided of the molybdenum- and tungsten-containing enzymes that
      catalyze the interconversion of formate and CO2 , focusing on common structural
      and mechanistic themes, as well as a consideration of the manner in which the
      mature Mo- or W-containing cofactor is inserted into apoprotein.

PMID- 30120800
TI  - Blastema formation and periosteal ossification in the regenerating adult mouse
      digit.
AB  - While mammals cannot regenerate amputated limbs, mice and humans have
      regenerative ability restricted to amputations transecting the digit tip,
      including the terminal phalanx (P3). In mice, the regeneration process is
      epimorphic and mediated by the formation of a blastema comprised of
      undifferentiated proliferating cells that differentiate to regenerate the
      amputated structures. Blastema formation distinguishes the regenerative response
      from a scar-forming healing response. The mouse digit tip serves as a preclinical
      model to investigate mammalian blastema formation and endogenous regenerative
      capabilities. We report that P3 blastema formation initiates prior to epidermal
      closure and concurrent with the bone histolytic response. In this early healing
      response, proliferation and cells entering the early stages of osteogenesis are
      localized to the periosteal and endosteal bone compartments. After the completion
      of stump bone histolysis, epidermal closure is completed and cells associated
      with the periosteal and endosteal compartments blend to form the blastema proper.
      Osteogenesis associated with the periosteum occurs as a polarized progressive
      wave of new bone formation that extends from the amputated stump and restores
      skeletal length. Bone patterning is restored along the proximal-distal and medial
      digit axes, but is imperfect in the dorsal-ventral axis with the regeneration of
      excessive new bone that accounts for the enhanced regenerated bone volume noted
      in previous studies. Periosteum depletion studies show that this compartment is
      required for the regeneration of new bone distal to the original amputation
      plane. These studies provide evidence that blastema formation initiates early in
      the healing response and that the periosteum is an essential tissue for
      successful epimorphic regeneration in mammals.

PMID- 30120801
TI  - Local production of prolactin in lesions may play a pathogenic role in psoriatic
      patients and imiquimod-induced psoriasis-like mouse model.
AB  - Human prolactin (PRL) is a well-known hormone for pituitary of lactation and
      reproduction, but it also has immunostimulatory effect in some inflammatory or
      autoimmune diseases including psoriasis, which has not been well elucidated. This
      study aimed to determine the relationship between PRL and psoriasis through
      clinical case-control studies, and explore the function of PRL in the
      pathogenesis of imiquimod (IMQ)-induced psoriasis-like mouse model. Serum from
      patients with psoriasis vulgaris (PsV), patients with erythrodermic psoriasis,
      and healthy controls (HCs) were collected for PRL test. Skin biopsies were
      collected for PRL, PRL receptors (PRLRs), cytokines mRNA level determination, PRL
      immunohistochemistry and PRL Western blotting. Mice were divided into four groups
      (each n = 6): control group (CON), IMQ group, anti-PRL group and solvent group.
      Anti-PRL group and solvent group mice were treated with PRL antagonist
      (cabergoline) and the solvent (0.25% methylcellulose) separately. The serum PRL
      level of PsV patients was significantly higher than that of HCs (P < 0.001).
      Compared with HCs, the mRNA levels of PRL and Th1/Th17 cytokines in skin lesions
      increased significantly (P < 0.05), and the PRL protein level was also
      significantly elevated in the epidermis and dermis of PsV patients. In IMQ
      induced psoriasis-like mouse model, the mRNA and protein levels of PRL in skin
      lesions were significantly higher than CON group (P < 0.01). Comparing to solvent
      group, serum PRL level and PRL, cytokines mRNA levels in skin lesions all
      decreased significantly and the skin inflammatory condition was also alleviated
      obviously in anti-PRL group. This study suggests that local production of PRL is
      the main resource of PRL in skin lesions and may play an important role in skin
      inflammatory of psoriasis.

PMID- 30120802
TI  - Warming enhances sedimentation and decomposition of organic carbon in shallow
      macrophyte-dominated systems with zero net effect on carbon burial.
AB  - Temperatures have been rising throughout recent decades and are predicted to rise
      further in the coming century. Global warming affects carbon cycling in
      freshwater ecosystems, which both emit and bury substantial amounts of carbon on
      a global scale. Currently, most studies focus on the effect of warming on overall
      carbon emissions from freshwater ecosystems, while net effects on carbon budgets
      may strongly depend on burial in sediments. Here, we tested whether year-round
      warming increases the production, sedimentation, or decomposition of particulate
      organic carbon and eventually alters the carbon burial in a typical shallow
      freshwater system. We performed an indoor experiment in eight mesocosms dominated
      by the common submerged aquatic plant Myriophyllum spicatum testing two
      temperature treatments: a temperate seasonal temperature control and a warmed (+4
      degrees C) treatment (n = 4). During a full experimental year, the carbon stock
      in plant biomass, dissolved organic carbon in the water column, sedimented
      organic matter, and decomposition of plant detritus were measured. Our results
      showed that year-round warming nearly doubled the final carbon stock in plant
      biomass from 6.9 +/- 1.1 g C in the control treatment to 12.8 +/- 0.6 g C (mean
      +/- SE), mainly due to a prolonged growing season in autumn. DOC concentrations
      did not differ between the treatments, but organic carbon sedimentation increased
      by 60% from 96 +/- 9.6 to 152 +/- 16 g C m-2  yaer-1 (mean +/- SE) from control
      to warm treatments. Enhanced decomposition of plant detritus in the warm
      treatment, however, compensated for the increased sedimentation. As a result, net
      carbon burial was 40 +/- 5.7 g C m-2  year-1 in both temperature treatments when
      fluxes were combined into a carbon budget model. These results indicate that
      warming can increase the turnover of organic carbon in shallow macrophyte
      dominated systems, while not necessarily affecting net carbon burial on a system
      scale.

PMID- 30120803
TI  - Metabolic and performance-related consequences of exercising at and slightly
      above MLSS.
AB  - Exercising at the maximal lactate steady state (MLSS) results in increased but
      stable metabolic responses. We tested the hypothesis that even a slight increase
      above MLSS (10 W), by altering the metabolic steady state, would reduce exercise
      performance capacity. Eleven trained men in our study performed: one ramp
      incremental tests; two to four 30-minute constant-load cycling exercise trials to
      determine the PO at MLSS (MLSSp ), and ten watts above MLSS (MLSSp+10 ), which
      were immediately followed by a time-to-exhaustion test; and a time-to-exhaustion
      test with no-prior exercise. Pulmonary O2 uptake V.O2 ) and blood lactate
      concentration ([La- ]b ) as well as local muscle O2 extraction ([HHb]) and muscle
      activity (EMG) of the vastus lateralis (VL) and rectus femoris (RF) muscles were
      measured during the testing sessions. When exercising at MLSSp+10 , although V.O2
      was stable, there was an increase in ventilatory responses and EMG activity,
      along with a non-stable [La- ]b response (P < 0.05). The [HHb] of VL muscle
      achieved its apex at MLSSp with no additional increase above this intensity,
      whereas the [HHb] of RF progressively increased during MLSSp+10 and achieved its
      apex during the time-to-exhaustion trials. Time-to-exhaustion performance was
      decreased after exercising at MLSSp (37.3 +/- 16.4%) compared to the no-prior
      exercise condition, and further decreased after exercising at MLSSp+10 (64.6 +/-
      6.3%) (P < 0.05). In summary, exercising for 30 min slightly above MLSS led to
      significant alterations of metabolic responses which disproportionately
      compromised subsequent exercise performance. Furthermore, the [HHb] signal of VL
      seemed to achieve a "ceiling" at the intensity of exercise associated with MLSS.

PMID- 30120804
TI  - Superoxide dismutase from venom of the ectoparasitoid Scleroderma guani inhibits
      melanization of hemolymph.
AB  - Superoxide dismutase (SOD) known as an important antioxidative stress protein has
      been recently found in venoms of several parasitoid wasps. However, its functions
      and characteristics as a virulent factor remain scarcely described. Here, we
      report the characterization of two venomous SOD genes (SguaSOD1 and SguaSOD3)
      from the ectoparasitoid, Scleroderma guani. The metal binding sites, cysteine
      amino acid positions and signature sequences of the SOD family were conserved
      within SguaSOD1 and SguaSOD3. Relatively high levels of their transcripts were
      observed in pupae followed a decrease in early adults, after which they had the
      highest transcriptions, indicating that their productions would be regulated in
      venom apparatus. Although the two genes showed lower expression in venom
      apparatus compared to head and thorax, the enzymatic assay revealed that SOD
      indeed had activity in venom. Further, we showed that recombinant SguaSOD3
      suppressed melanization of host hemolymph, implying that this protein used as a
      virulent factor uniquely impacts the prophenoloxidase cascade.

PMID- 30120805
TI  - Electrospray ionization tandem mass spectrometry of labdane-type acid diterpenes.
AB  - Copaifera (Leguminoseae) species produce a commercially interesting oleoresin
      that displays several biological activities, including antimicrobial and anti
      inflammatory properties. Labdane-type diterpenes are the main chemical
      constituents of these oleoresins, and copalic acid is the only compound that has
      been detected in all Copaifera oleoresins. In this study, we investigate some
      aspects of the gas-phase fragmentation reactions involved in the formation of the
      product ions from the deprotonated compounds (-)-ent-copalic acid (1), (-)-ent
      3beta-hydroxy-copalic acid (2), (-)-ent-3beta-acetoxy-copalic acid (3), and (-)
      ent-agathic acid (4) by electrospray ionization tandem mass spectrometry (ESI
      MS/MS) and multiple stage mass spectrometry (MSn ). Our results reveal that the
      product ion with m/z 99 is common to all the analyzed compounds, whereas the
      product ion with m/z 217 is diagnostic for compounds 2 and 3. Moreover, only
      compound 4 undergoes CO2 (44 u) and acetic acid (60 u) elimination from the
      precursor ion. Thermochemical data obtained by computational chemistry at the
      B3LYP/6-31G(d) level of theory support the proposed ion structures. These data
      helped us to identify these compounds in a crude commercial Copaifera
      langsdorffii oleoresin by selective multiple reaction monitoring (MRM). Finally,
      a precursor ion scan (PIS) strategy aided screening of labdane-type acid
      diterpenes other than 1 to 4 in the same Copaifera oleoresin sample and led us to
      propose the structures of 8,17-dihydro-ent-agathic acid (5) and 3-keto-ent
      copalic acid (6), which have not been previously reported in Copaifera
      oleoresins.

PMID- 30120806
TI  - Predictive value of ultrasound scoring in relation to clinical and histological
      parameters in xerostomia patients.
AB  - BACKGROUND: Salivary gland dysfunction is one of the main clinical features of
      Sjogren's syndrome (SS), manifested by xerostomia with subsequent complications
      and well-established effects on the person's quality of life. OBJECTIVES: To
      determine firstly whether selected tests of salivary gland function and
      structure, unstimulated whole salivary flow rate (UWSFR), parotid flow rate
      (PFR), clinical oral dryness score (CODS) and ultrasound score (USS), can
      discriminate SS from non-SS sicca patients and secondly whether these tests can
      differentiate between patients in different subgroups of SS. METHOD: Unstimulated
      whole salivary flow rate, PFR, CODS and USS were determined in 244 patients
      comprised of SS patients (n = 118), SS patients at higher risk of lymphoma (n =
      30) or with lymphoma (n = 26), and non-SS sicca disease controls (n = 70).
      RESULTS: All assessments showed a significant difference between the overall SS
      group and the disease control group, attributed mainly to the lymphoma subgroups
      of SS (p < 0.0001 for all parameters). There was a significant correlation
      (Spearman r = 0.7, p value <0.0001) and 87.3% agreement between USS and the
      histology focus scores of 119 patients. CONCLUSION: The results suggest that
      salivary gland tests including USS can aid in differentiating between SS and non
      SS dry mouth, especially the subgroups of SS with lymphoma or at higher risk of
      developing lymphoma.

PMID- 30120808
TI  - Chikungunya in solid organ transplant recipients, a case series and literature
      review.
AB  - Chikungunya virus is a recent emerging arbovirus in Latin America, and the
      clinical manifestations can vary from fever and rash to severe chronic
      inflammatory arthritis. Few reports have been published regarding this infection
      in immunocompromised patients, including solid organ transplant recipients. We
      report a case series of solid organ transplant recipients with confirmed
      Chikungunya infection by positive reverse transcription polymerase chain reaction
      (RT-PCR), identified between January 2014 and December 2016. In addition, we
      conducted a literature review searching PubMed, EMBASE, and LILACS databases on
      Chikungunya infection in solid organ transplant recipients. Ten solid organ
      transplant recipients were included, consisting of 5 kidney, 4 liver, and 1
      liver/kidney transplant recipient. Mean age of the transplant recipients was 47
      years, and the most frequent symptoms of Chikungunya infection were arthralgia
      and fever. None of the patients required treatment in the intensive care unit, no
      deaths or graft rejection occurred. None of our patients had recurrent arthritis
      during 3-month follow-up period after the infection. Twenty-one cases of
      Chikungunya virus were identified in the literature review. Most cases had a
      benign clinical course with no severe complications, death, or chronic
      inflammatory arthritis. In conclusion, Chikungunya infection in solid organ
      transplant recipients has a benign course and has no chronic recurrent arthritis.
      It is possible that the immunosuppression regimen could decrease the risk of
      severe or chronic inflammatory manifestations in solid organ transplant
      recipients infected with Chikungunya.

PMID- 30120807
TI  - The effect of dietary amylose/amylopectin ratio on serum and hepatic lipid
      content and its molecular mechanisms in growing-finishing pigs.
AB  - This study was conducted to investigate the effects of dietary
      amylose/amylopectin ratio (DAR) on serum and hepatic lipid content, luminal short
      chain fatty acid (SCFA) concentrations, and the expression of host genes involved
      in fat and glucose metabolism in liver and mucosa in growing-finishing pigs.
      Forty-eight Duroc * Landrace * Large White pigs (49.8 +/- 2.8 kg) were randomly
      allocated to low amylose/amylopectin ratio (LR) and high amylose/amylopectin
      ratio (HR) groups, each group consisting of six replicates (pen) with four pigs
      per pen. The DAR was 12/88 for LR and 30/70 for HR. Experiment lasted for 67
      days. Results showed that, compared with HR group, ingestion of LR significantly
      increased the liver total lipid and cholesterol concentration (p < .05) and
      decreased the serum LDL-C concentration (p < .05). The concentration of
      propionate, butyrate and total SCFAs in caecum digesta was significantly lower in
      LR group than in HR group (p < .05). We observed a significant increase in
      glucose transporter 2 (GLUT2), sodium-dependent glucose transporter 1 (SGLT1)
      gene expression in LR-fed pigs in the jejunum mucosa (p < .01). A decrease in Na+
      coupled monocarboxylate transporter (SMCT1) and free fatty acid receptor 3
      (FFAR3) expression was found in the ileum mucosa with LR group (p < .05).
      Ingestion of LR diet significantly decreased the hexokinase (p < .01) and tend to
      decrease the pyruvate kinase (p = .050) activities in the liver. Meanwhile, the
      present results indicated that ingestion of LR diet significantly increased the
      transcription of gluconeogenesis and lipogenic genes such as forkhead box O1
      (FOXO1), fatty acid synthetase3 (FAS3) (p < .05). These findings demonstrated
      that high amylopectin has harmful effects on hepatic lipid deposit through the
      modulation of the liver Foxo1 signalling and should be avoided from one's diet.

PMID- 30120809
TI  - A cross-sectional survey of mental health service users', carers' and
      professionals' priorities for patient safety in the United Kingdom.
AB  - BACKGROUND: Establishing patient safety priorities in psychiatry has received
      less international attention than in other areas of health care. This study aimed
      to identify safety issues as described by people in the United Kingdom
      identifying as mental health service users, carers and professionals. METHODS: A
      cross-sectional online survey was distributed via social media. Identified safety
      issues were mapped onto the Yorkshire Contributory Factors Framework (YCFF) which
      categorizes factors that contribute to patient safety incidents in general
      hospital settings. Service user and carer responses were described separately
      from professional responses using descriptive statistics. RESULTS: One hundred
      and eighty-five responses from 95 service users and carers and 90 professionals
      were analysed. Seventy different safety issues were identified. These were mapped
      onto the 17 existing categories of the YCFF and two additional categories created
      to form the YCFF-MH. Most frequently identified issues were as follows:
      "Individual characteristics" (of staff) which included competence and listening
      skills; "Service process" that contained concerns about waiting times;
      "Management of staff and staffing levels" dominated by staffing levels; and
      "External policy context" which included the overall resourcing of services.
      Professionals identified staffing levels and inadequate community provision more
      frequently than service users and carers, who in turn identified crisis care more
      frequently. CONCLUSIONS: This study updates knowledge on stakeholder perceived
      safety issues across mental health care. It shows a far broader range of issues
      relating to safety than has previously been described. The YCFF was successfully
      modified to describe these issues and areas for further coproduced research are
      suggested.

PMID- 30120811
TI  - Role of IL-17A receptor blocking in melanocyte survival: A strategic intervention
      against vitiligo.
AB  - Cytokines regulate immune response and inflammation and play an important role in
      depigmentation process of an autoimmune disease, vitiligo. We sought to determine
      how inflammatory cytokines influence the progression of vitiligo, and based on
      that, we develop a logical therapeutic intervention using primary melanocyte
      culture. Melanocytes were cultured and exposed to IL-17A, IL-1beta, IFN-gamma and
      TGF-beta for 4 days. Melanocytes proliferation, tyrosinase assay and melanin
      content were measured. Real-Time PCR was used to analyse mRNA expression of genes
      specific for melanocytes growth and pigmentation. Anti-IL-17A receptor antibody
      was used to block IL-17A receptors expressed on melanocytes. Protein expression
      of MITF and TYR was assessed by immunofluorescence and Western blotting. A
      gradual decline in the melanocyte population, melanin content and tyrosinase
      activity was observed after different cytokine treatment. The expression of MITF
      and its downstream genes after blocking with anti-IL-17RA, an increased melanin
      content, increased expression of TYR, MITF along with its downstream genes, and
      cell proliferation was observed.

PMID- 30120812
TI  - Liraglutide and weight loss among patients with advanced heart failure and a
      reduced ejection fraction: insights from the FIGHT trial.
AB  - AIMS: Obesity is present in up to 45% of patients with heart failure (HF).
      Liraglutide, a glucagon-like peptide-1 (GLP-1) receptor antagonist, facilitates
      weight loss in obese patients. The efficacy of liraglutide as a weight loss agent
      among patients with HF and reduced ejection fraction (HFrEF) and a recent acute
      HF hospitalization remains unknown. METHODS AND RESULTS: The Functional Impact of
      GLP-1 for Heart Failure Treatment study randomized 300 patients with HFrEF
      (ejection fraction <= 40%), both with and without diabetes and a recent HF
      hospitalization to liraglutide or placebo. The primary outcome for this post hoc
      analysis was the change in weight from baseline to last study visit. We conducted
      an 'on-treatment' analysis of patients with at least one follow-up visit on study
      drug (123 on liraglutide and 124 on placebo). The median age was 61 years, 21%
      were female, and 69% of patients had New York Heart Association functional Class
      III or IV symptoms. The median ejection fraction was 25% (25th, 75th percentile
      19-32%). Liraglutide use was associated with a significant weight reduction
      [liraglutide -1.00 lbs vs. placebo 2.00 lbs; treatment difference -4.10 lbs; 95%
      confidence interval (CI) -7.94, -0.25; P = 0.0367; percentage treatment
      difference -2.07%, 95% CI -3.86, -0.28; P = 0.0237]. Similar results were seen
      after multivariable adjustments. Liraglutide also significantly reduced
      triglyceride levels (liraglutide 7.5 mg/dL vs. placebo 12.0 mg/dL; treatment
      difference -33.1 mg/dL; 95% CI -60.7, -5.6; P = 0.019). CONCLUSIONS: Liraglutide
      is an efficacious weight loss agent in patients with HFrEF. These findings will
      require further exploration in a well-powered cardiovascular outcomes trial.

PMID- 30120813
TI  - Impaired social contacts with familiar anesthetized conspecific in CA3-restricted
      brain-derived neurotrophic factor knockout mice.
AB  - Familiarity is conveyed by social cues and determines behaviors toward
      conspecifics. Here, we characterize a novel assay for social behaviors in mice
      contacts with anesthetized conspecific-which eliminates reciprocal interactions,
      including intermale aggression and shows behaviors that are independent of the
      demonstrator's activity. During the initial 10 minutes (phase-1), the wild-type
      (WT) subjects contacted the anesthetized conspecifics vigorously regardless of
      familiarity. During the subsequent 80 minutes (phase-2), however, they contacted
      more with familiar than unfamiliar conspecifics. We then applied this test to
      highly aggressive mice with a hippocampal CA3-restricted knockout (KO) of brain
      derived neurotrophic factor (BDNF), in which aggression may mask other social
      behaviors. The KO mice showed less preference for contacting familiar
      conspecifics than did WT mice during phase-2 but no differences during phase-1.
      Among nonsocial behaviors, WT mice also spent less time eating in the presence of
      familiar than with unfamiliar conspecifics, which was not seen in KO mice. In
      addition, KO mice exhibited reduced pain sensitization. Altogether, these
      findings suggest that CA3-specific deletion of BDNF results in deficits in
      circuits that process social cues from familiar conspecifics as well as pain and
      may underlie empathy-like behaviors.

PMID- 30120815
TI  - Reply.

PMID- 30120814
TI  - General and sex profile of women with partner affected by premature ejaculation:
      results of a large observational, non-interventional, cross-sectional,
      epidemiological study (IPER-F).
AB  - BACKGROUND: Couple distress is a crucial point in premature ejaculation (PE). PE
      has been associated with significant bother, interpersonal problems, and
      dissatisfaction with sexual intercourse for both men and their partners.
      OBJECTIVES: The primary objective of this study was to assess the effect of PE on
      female sexuality in female partners of men affected from PE. Secondary objectives
      were to assess the impact of PE on female sexual quality of life, to assess the
      presence of sexual problems of the male partner, and to evaluate the prevalence
      and characteristics of comorbidities. MATERIALS AND METHODS: Adult women aged 18
      to 80 years old, sexually active, were randomly sampled from the patient lists of
      General Practitioners in Italy and were included in this observational, non
      interventional, cross-sectional epidemiological study. Subjects were asked to
      fill: a general questionnaire regarding anthropometric data, lifestyle, marital
      status, education, occupation, economic conditions, general health status,
      comorbidities, and sexual habits; the Sexual Quality of Life Questionnaire-Female
      (SQoL-F); the Female Sexual Distress Scale (FSDS-R-PE); the Self-rating
      Depression Scale (SDS); and Self-rating Anxiety Scale (SAS). In addition, females
      reported about their partner's ejaculation time and the presence of sexual
      dysfunctions. RESULTS: A total of 3,104 women were included. Mean age was 45.1
      years. Woman with PE partners presented a higher percentage of sexual dysfunction
      and reported more anxiety compared with female partners of men not affected from
      PE (42.69% vs. 20.56% and 30.95% vs. 15,34%, respectively). In addition, they
      referred more sexual dysfunction in their partners. Hypertension,
      hypercholesterolemia, arthritis, heart diseases, thyroid disease, a history of
      menopause, or hysterectomy resulted in significantly more prevalence in women
      with PE partners. DISCUSSION AND CONCLUSIONS: Female partners of PE patients
      present an increased prevalence of sexual distress, a reduced quality of sexual
      life, and an increased anxiety score when compared to women whose partners are
      not affected from PE.

PMID- 30120810
TI  - T-complex protein 1-ring complex enhances retrograde axonal transport by
      modulating tau phosphorylation.
AB  - The cytosolic chaperonin T-complex protein (TCP) 1-ring complex (TRiC) has been
      shown to exert neuroprotective effects on axonal transport through clearance of
      mutant Huntingtin (mHTT) in Huntington's disease. However, it is presently
      unknown if TRiC also has any effect on axonal transport in wild-type neurons.
      Here, we examined how TRiC impacted the retrograde axonal transport of brain
      derived neurotrophic factor (BDNF). We found that expression of a single TRiC
      subunit significantly enhanced axonal transport of BDNF, leading to an increase
      in instantaneous velocity with a concomitant decrease in pauses for retrograde
      BDNF transport. The transport enhancing effect by TRiC was dependent on
      endogenous tau expression because no effect was seen in neurons from tau knockout
      mice. We showed that TRiC regulated the level of cyclin-dependent kinase 5
      (CDK5)/p35 positively, contributing to TRiC-mediated tau phosphorylation (ptau).
      Expression of a single TRiC subunit increased the level of ptau while
      downregulation of the TRiC complex decreased ptau. We further demonstrated that
      TRiC-mediated increase in ptau induced detachment of tau from microtubules. Our
      study has thus revealed that TRiC-mediated increase in tau phosphorylation
      impacts retrograde axonal transport.

PMID- 30120816
TI  - Vamorolone treatment improves skeletal muscle outcome in a critical illness
      myopathy rat model.
AB  - AIM: Critical illness myopathy (CIM) is a consequence of modern critical care,
      leading to skeletal muscle atrophy/paralysis with negative consequences for
      mortality/morbidity and health care costs. Glucocorticoids (GCs) have been
      proposed to trigger CIM. Here, we compare outcomes of two GCs, the commonly used
      prednisolone and the newly developed dissociative vamorolone in response to the
      intensive care unit (ICU) condition for 5 days, ie, sedation, immobilization, and
      mechanical ventilation. METHODS: Rats were divided into a 0-day sham-operated
      control group, and three groups exposed to 5 days ICU condition during treatment
      with prednisolone (PRED) or vamorolone (VAM) or none of these GCs (ICU-group).
      Survival, body and muscle weights, cytokine concentrations, regulation of muscle
      contraction in single fast- and slow-twitch muscle fibres, myofibrillar protein
      expression and protein degradation pathways were studied. RESULTS: Critical
      illness myopathy geno- and pheno-types were confirmed in the ICU group. However,
      VAM and PRED groups showed reduced atrophy/weakness than the ICU group, and
      muscle specific differences with more severe negative effects on fast-twitch
      muscle fibres in the PRED than the other groups. CONCLUSION: These results show
      that vamorolone provides a GC intervention superior to typical GCs in improving
      CIM outcomes. Further, the findings do not support the notion that moderate-dose
      GC treatment represents a factor triggering CIM.

PMID- 30120819
TI  - Water is life.

PMID- 30120817
TI  - Palliative radiation therapy (RT) for prostate cancer patients with bone
      metastases at diagnosis: A hospital-based analysis of patterns of care, RT
      fractionation scheme, and overall survival.
AB  - Prostate cancer (PCa) is one of the most common malignancies associated with bone
      metastases, and palliative radiation therapy (RT) is an effective treatment
      option. A total of 2641 patients were identified with PCa and bone metastases at
      diagnosis from 2010 to 2014 in the NCDB. Fractionation scheme was designated as
      short course ([SC-RT]: 8 Gy in 1 fraction and 20 Gy in 5 fractions) vs long
      course ([LC-RT]: 30 Gy in 10 fractions and 37.5 Gy in 15 fractions). Patient
      characteristics were correlated with fractionation scheme using logistic
      regression. Overall survival was analyzed using the Kaplan-Meier method, log-rank
      test, Cox proportional hazards models, and propensity score-matched analyses. A
      total of 2255 (85.4%) patients were included in the LC-RT group and 386 (14.6%)
      patients in the SC-RT group. SC-RT was more common in patients over 75 years age
      (odds ratio [OR]: 1.70, 95% confidence interval [CI] 1.32-2.20), treatment at an
      academic center (OR: 1.76, 1.20-2.57), living greater than 15 miles distance to
      treatment facility (OR: 1.38, 1.05-1.83), treatment to the rib (OR: 2.99, 1.36
      6.60), and in 2014 (OR: 1.73, 1.19-2.51). RT to the spine was more commonly long
      course (P < .0001). In the propensity-matched cohort, LC-RT was associated with
      improved OS (P < .0001), but no OS difference was observed between 37.5 Gy and
      either 8 Gy in one fraction or 20 Gy in 5 fractions (P > .5). LC-RT remains the
      most common treatment fractionation scheme for palliative bone metastases in PCa
      patients. Use of palliative SC-RT is increasing, particularly in more recent
      years, for older patients, treatment at academic centers, and with increasing
      distance from a treatment center.

PMID- 30120818
TI  - The national and provincial burden of medically attended influenza-associated
      influenza-like illness and severe acute respiratory illness in the Democratic
      Republic of Congo, 2013-2015.
AB  - BACKGROUND: Estimates of influenza-associated outpatient consultations and
      hospitalizations are severely limited in low- and middle-income countries,
      especially in Africa. METHODS: We conducted active prospective surveillance for
      influenza-like illness (ILI) and severe acute respiratory illness (SARI) at 5
      healthcare facilities situated in Kinshasa Province during 2013-2015. We tested
      upper respiratory tract samples for influenza viruses using a reverse
      transcription-polymerase chain reaction assay. We estimated age-specific numbers
      and rates of influenza-associated ILI outpatient consultations and SARI
      hospitalizations for Kinshasa Province using a combination of administrative and
      influenza surveillance data. These estimates were extrapolated to each of the
      remaining 10 provinces accounting for provincial differences in prevalence of
      risk factors for pneumonia and healthcare-seeking behavior. Rates were reported
      per 100 000 population. RESULTS: During 2013-2015, the mean annual national
      number of influenza-associated ILI outpatient consultations was 1 003 212 (95%
      Confidence Incidence [CI]: 719 335-1 338 050 - Rate: 1205.3; 95% CI: 864.2
      1607.5); 199 839 (95% CI: 153 563-254 759 - Rate: 1464.0; 95% CI: 1125.0-1866.3)
      among children aged <5 years and 803 374 (95% CI: 567 772-1 083 291 - Rate:
      1154.5; 95% CI: 813.1-1556.8) among individuals aged >=5 years. The mean annual
      national number of influenza-associated SARI hospitalizations was 40 361 (95% CI:
      24 014-60 514 - Rate: 48.5; 95% CI: 28.9-72.7); 25 452 (95% CI: 19 146-32 944 -
      Rate: 186.5; 95% CI: 140.3-241.3) among children aged <5 years and 14 909 (95%
      CI: 4868-27 570 - Rate: 21.4; 95% CI: 28.9-72.7) among individuals aged >=5
      years. CONCLUSIONS: The burden of influenza-associated ILI outpatient
      consultations and SARI hospitalizations was substantial and was highest among
      hospitalized children aged <5 years.

PMID- 30120821
TI  - Impact of Maternal BMI on Rubella Nonimmunity at Antenatal Screening.
AB  - OBJECTIVE: The aim of this study was to examine the relationship between BMI and
      the incidence of rubella nonimmunity among pregnant women with regard to the
      World Health Organization categories. METHODS: This was a retrospective cohort
      study of 117,063 eligible gravidas, managed between 1998 and 2015 in a university
      hospital of Hong Kong, China. BMI at antenatal booking was banded using the
      following World Health Organization definitions: < 18.5 kg/m2 , 18.5 to 24.9
      kg/m2 , 25.0 to 29.9 kg/m2 , and >=30.0 kg/m2 . Maternal rubella nonimmunity
      status by BMI was assessed. Incidence rates were also assessed after adjusting
      for maternal advanced age, short stature < 151 cm, mothers' birthplace, and
      postobstetric history covariates. RESULTS: Rubella nonimmunity incidence
      increased as the BMI increased (P < 0.001). Gravidas with high BMI were more
      likely to be nonimmune if born in Hong Kong (odds ratio [OR], 1.234; 95% CI:
      1.159-1.315; P < 0.001) compared with those born outside of Hong Kong (OR, 1.066;
      95% CI: 0.997-1.141; P = 0.063). After adjusting for covariates, women with BMI
      >= 25 kg/m2 had 1.127 (P < 0.001; 95% CI: 1.074-1.182) greater odds of being
      nonimmune. CONCLUSIONS: High maternal BMI (>= 25.0 kg/m2 ) is associated with
      reduced rubella immunity, an effect confined to gravidas with almost complete
      vaccine coverage in childhood.

PMID- 30120820
TI  - Genome-wide screening of budding yeast with honokiol to associate mitochondrial
      function with lipid metabolism.
AB  - Honokiol (HNK), an important medicinal component of Magnolia officinalis, is
      reported to possess pharmacological activities against a variety of diseases.
      However, the molecular mechanisms of HNK medicinal functions are not fully clear.
      To systematically study the mechanisms of HNK action, we screened a yeast mutant
      library based on the conserved nature of its genes among eukaryotes. We
      identified genes associated with increased resistance or sensitivity to HNK after
      mutation. After functional classification of these genes, we found that most HNK
      resistant strains in the largest functional category were petites with mutations
      in mitochondrial genes, indicating that mitochondria were related to HNK
      resistance. Additional analysis showed that resistance of petite mutants to HNK
      was associated with upregulation of the ATP-binding cassette transporter Pdr5,
      which pumps out HNK. We also found that several HNK-sensitive mitochondria
      mutants were not petites, and had larger lipid droplets (LDs). Furthermore, HNK
      treatment on wild-type yeast cells seemed to disrupt mitochondrial morphology,
      induced triacylglycerol synthesis, and generated supersized LDs surrounded by
      mitochondria and endoplasmic reticulum (ER). These changes are also applied to
      atp7Delta mutant if no carbon resource was available. These results suggested
      that HNK treatment partly impaired normal mitochondrial function to form larger
      LDs by altering lipid metabolism.

PMID- 30120822
TI  - Review article: Common emergency department presenting complaints of prisoners: A
      systematic review.
AB  - Prisoners are a particularly vulnerable minority group whose healthcare needs and
      management differ substantially from the general population. The overall burden
      of disease of prisoners is well documented; however, little is known regarding
      the aetiology and frequency of prisoners' acute medical complaints requiring an
      ED visit. Objectives of the review were to identify, review and appraise existing
      literature regarding prisoners' presentations to EDs. We performed systematic
      electronic searches in MEDLINE, EMBASE, PsycINFO, PubMed, Cochrane, and Web of
      Science using MeSH terms and keywords. Two reviewers abstracted data and
      conducted quality appraisal using the Quality Assessment Tool for Observational
      Cohort and Cross-Sectional Studies. Nine articles met the predefined inclusion
      criteria. Apart from two European studies in the past 5 years, there is a
      scarcity of literature primarily addressing the common presenting complaints to
      EDs by prisoners. Existing studies demonstrated that prisoners have a
      disproportionately high burden of traumatic, infectious and psychiatric disease
      requiring emergency treatment. With the increasing number of emergency
      presentations made by prisoners each year, it is vital that further research is
      undertaken to identify trends of these acute medical complaints in order to
      ensure optimal therapeutic outcomes for prisoners.

PMID- 30120823
TI  - Practical Ways to Achieve Targets in Diabetes Care.
AB  - Peter J. Rentzepis, Martin J. Kurian, Ann M. Carracher, and Kelly L. Close are of
      Close Concerns (http://www.closeconcerns.com), a healthcare information company
      focused exclusively on diabetes and obesity care. Close Concerns publishes Closer
      Look, a periodical that brings together news and insights in these areas. Each
      month, the Journal of Diabetes includes this News feature, in which Rentzepis,
      Kurian, Carracher, and Close review the latest developments relevant to
      researchers and clinicians.

PMID- 30120825
TI  - Adjusting Insulin Delivery to Activity (AIDA) clinical trial: Effects of activity
      based insulin profiles on glucose control in children with type 1 diabetes.
AB  - BACKGROUND: Increased daytime activity in children with type I diabetes mellitus
      (T1DM) is associated with increased risk of hypoglycemia. OBJECTIVE: To determine
      whether an automated weekly review of accelerometer, continuous glucose
      monitoring (CGM), and insulin pump data, could be used to identify children with
      increased risk of nighttime hypoglycemia and preemptively adjust the nighttime
      basal insulin profile according to daytime activity. RESEARCH AND DESIGN METHODS:
      Clinical trial of children with T1DM on insulin pump and CGM therapy. Subjects at
      risk of nighttime hypoglycemia were identified from regression analysis of
      daytime step count vs nighttime nadir glucose. If the regression slope was
      significantly different from zero (P < 0.05) subjects were managed with different
      algorithm derived nighttime basal insulin profiles following high and low
      activity days. RESULTS: Twenty children (median age: 12; range: 7-17 years) were
      enrolled. Regression slopes were significant in 10 children. In these children,
      baseline nighttime nadir glucose level was lower following high activity days
      (120 [110-139] vs 152 [130-162] mg/dL, P = 0.004). Use of activity-based
      nighttime basal profiles produced similar nighttime nadir glucose levels
      following high and low activity days (136 [123-175] vs 140 [108-180] mg/dL, P =
      0.73) with fewer nighttime interventions to correct hypoglycemia (0 [0-0.16] vs
      0.15 [0.13-0.22] per night, P = 0.008). CONCLUSION: Children with lower nighttime
      glucose levels following high daytime activity can be identified using step count
      data obtained from readily available accelerometers and the nighttime glucose
      control improved using different activity-based basal profiles.

PMID- 30120824
TI  - Construction of a recombinant rhinovirus accommodating fluorescent marker
      expression.
AB  - BACKGROUND: Rhinovirus (RV) causes the common cold and asthma exacerbations. The
      RV genome is a 7.3 kb single-strand positive-sense RNA. OBJECTIVE: Using minor
      group RV1A as a backbone, we sought to design and generate a recombinant RV1A
      accommodating fluorescent marker expression, thereby allowing tracking of viral
      infection. METHOD: Recombinant RV1A infectious cDNA clones harboring the coding
      sequence of green fluorescent protein (GFP), Renilla luciferase, or iLOV (for
      light, oxygen, or voltage sensing) were engineered and constructed. RV-infected
      cells were determined by flow cytometry, immunohistochemistry, and
      immunofluorescence microscopy. RESULTS: RV1A-GFP showed a cytopathic effect in
      HeLa cells but failed to express GFP or Renilla luciferase due to deletion. The
      smaller fluorescent protein construct, RV1A-iLOV, was stably expressed in
      infected cells. RV1A-iLOV expression was used to examine the antiviral effect of
      bafilomycin in HeLa cells. Compared to parental virus, RV1A-iLOV infection of
      BALB/c mice yielded a similar viral load and level of cytokine mRNA expression.
      However, imaging of fixed lung tissue failed to reveal a fluorescent signal,
      likely due to the oxidation and bleaching of iLOV-bound flavin mononucleotide. We
      therefore employed an anti-iLOV antibody for immunohistochemical and
      immunofluorescence imaging. The iLOV signal was identified in airway epithelial
      cells and CD45+ CD11b+ lung macrophages. CONCLUSIONS: These results suggest that
      RV1A-iLOV is a useful molecular tool for studying RV pathogenesis. The
      construction strategy for RV1A-iLOV could be applied to other RV serotypes.
      However, the detection of iLOV-expressing RV in fixed tissue required the use of
      an anti-iLOV antibody, limiting the value of this construct.

PMID- 30120826
TI  - Contrast-enhanced photoacoustic imaging in the second near-infrared window using
      semiconducting polymer nanoparticles.
AB  - Photoacoustic imaging (PAI) is a fast growing deep-tissue imaging modality.
      However, light scattering and absorption in biological tissues limit imaging
      depth. Short near-infrared wavelengths (650 to 950 nm) are widely used for PAI.
      Using longer near-infrared wavelengths reduces scattering. We demonstrate deep
      tissue contrast-enhanced in vivo photoacoustic imaging at a wavelength of 1064
      nm. An ultranarrow bandgap semiconducting polymer poly (thienoisoindigo-alt
      diketopyrrolopyrrole) (denoted as PIGD) is designed and demonstrated for imaging
      at 1064 nm. By embedding colloidal nanoparticles (NPs) of PIGD in chicken-breast
      tissue, an imaging depth of ~5  cm is achieved. Intravenous injection of PIGD NPs
      in living rats showed brain vascular images with ~2 times higher contrast
      compared with the brain vascular images without any contrast agent. Thus, PIGD
      NPs as an NIR-II contrast agent opens new opportunities for both preclinical and
      clinical imaging of deep tissues with enhanced contrast.

PMID- 30120827
TI  - Visualization of skin microvascular dysfunction of type 1 diabetic mice using in
      vivo skin optical clearing method.
AB  - To realize visualization of the skin microvascular dysfunction of type 1 diabetic
      mice, we combined laser speckle contrast imaging and hyperspectral imaging to
      simultaneously monitor the noradrenaline (NE)-induced responses of vascular blood
      flow and blood oxygen with the development of diabetes through optical clearing
      skin window. The main results showed that venous and arterious blood flow
      decreased without recovery after injection of NE; furthermore, the decrease of
      arterious blood oxygen induced by NE greatly weakened, especially for 2- and 4
      week diabetic mice. This change in vasoconstricting effect of NE was related to
      the expression of alpha1-adrenergic receptor. This study demonstrated that skin
      microvascular function was a potential research biomarker for early warning in
      the occurrence and development of diabetes. The in vivo skin optical clearing
      method provides a feasible solution to realize visualization of cutaneous
      microvessels for monitoring microvascular reactivity under pathological
      conditions. In addition, visual monitoring of skin microvascular function
      response has guiding significance for early diagnosis of diabetes and clinical
      research.

PMID- 30120828
TI  - Toward quantitative three-dimensional microvascular networks segmentation with
      multiview light-sheet fluorescence microscopy.
AB  - Three-dimensional (3-D) large-scale imaging of microvascular networks is of
      interest in various areas of biology and medicine related to structural,
      functional, developmental, and pathological issues. Light-sheet fluorescence
      microscopy (LSFM) techniques are rapidly spreading and are now on the way to
      offer operational solutions for large-scale tissue imaging. This contribution
      describes how reliable vessel segmentation can be handled from LSFM data in very
      large tissue volumes using a suitable image analysis workflow. Since capillaries
      are tubular objects of a few microns scale radius, they represent challenging
      structures to reliably reconstruct without distortion and artifacts. We provide a
      systematic analysis of multiview deconvolution image processing workflow to
      control and evaluate the accuracy of the reconstructed vascular network using
      various low to high level, metrics. We show that even if low-level structural
      metrics are sensitive to isotropic imaging enhancement provided by a larger
      number of views, functional high-level metrics, including perfusion permeability,
      are less sensitive. Hence, combining deconvolution and registration onto a few
      number of views appears sufficient for a reliable quantitative 3-D vessel
      segmentation for their possible use for perfusion modeling.

PMID- 30120830
TI  - Humoral and Cellular Immune Response of European Seabass Dicentrarchus labrax
      Vaccinated with Heat-Killed Mycobacterium marinum (iipA::kan Mutant).
AB  - No vaccine is yet commercially available against Mycobacterium marinum, the
      etiological agent of fish mycobacteriosis (also known as "fish tuberculosis").
      The mycobacterial gene responsible for invasion and intracellular persistence,
      iipA, is known to moderate M. marinum pathology in Zebrafish Danio rerio. Two
      doses of heat-killed, wild-type, virulent M. marinum and two doses of a heat
      killed, avirulent M. marinum iipA::kan mutant strain were used in parallel to
      vaccinate European Seabass Dicentrarchus labrax. The fish were then challenged
      with live, virulent M. marinum, and the pathogenesis of the infection was
      monitored. High specific immunoglobulin M (IgM) response and an increase in
      cytokine tumor necrosis factor alpha (TNF-alpha) messenger RNA expression levels
      were observed in all vaccinated fish. At 1 month postchallenge, TNF-alpha
      expression levels increased in spleen tissues of fish vaccinated with the
      virulent type and in those of unvaccinated fish, whereas in the head kidney,
      expression was up-regulated only in unvaccinated fish. The expression then
      decreased, and at 2 months postchallenge, expression appeared similar in all
      vaccination types. The highest survival rate (75%) was recorded in the group of
      fish that were vaccinated with a high dose of avirulent iipA::kan mutant. The
      iipA::kan mutant induced a strong immune response accompanied by only modest
      tissue disruption. Coupled with an effective program of booster treatments, the
      iipA::kan mutant vaccine may be developed into a powerful preventive measure
      against fish mycobacteriosis.

PMID- 30120829
TI  - Effect of Rehabilitation on Fatigue Level in Patients with Multiple Sclerosis.
AB  - BACKGROUND The objective of this study was to evaluate the effect of a
      rehabilitation program in changing the perception of fatigue in patients with
      multiple sclerosis. MATERIAL AND METHODS The study involved 65
      respondents/patients with clinically confirmed multiple sclerosis (54 women, 11
      men, average age 46.49 years). The evaluation of the effects of fatigue on the
      physical, psychological, and psychosocial aspects of life was assessed using the
      Modified Fatigue Impact Scale (MFIS). To test the effectiveness of the
      neurorehabilitation program, we enrolled 2 groups: the experimental group (EG,
      n=32, 29 women, 3 men, Expanded Disability Status Scale (EDSS) 4.8 average, SD+/
      1.77, min. 1.5 max 8.0) participated in the intervention and rehabilitation
      program over a period of 12 weeks and the control group (CG, n=33, 25 women, 8
      men. EDSS average 5.12+/-1.74 SD, min. 2.0 max. 8.0). Each group of patients was
      divided into 3 sub-groups according to the severity of EDSS: a) 1-3.5, b) 4-6,
      and c) 6.5-8. For the statistical evaluation of the significance of the observed
      changes, the MANOVA/ANOVA model was used. RESULTS Between the input and output
      assessment of the MFIS individual areas questionnaire between the EG and the CG,
      there existed a statistically significant in the physical area (p<0.000),
      psychological area (p<0.000), and psychosocial area (p=0.002). CONCLUSIONS Our
      results support the importance of an active approach in patients with multiple
      sclerosis using individualized rehabilitation intervention programs.

PMID- 30120831
TI  - Functional performance tests identify lateral ankle sprain risk: A prospective
      pilot study in adolescent soccer players.
AB  - Determining the clinical utility of functional performance tests (FPTs) and
      establishing cutoff scores could be useful in identifying those athletes who
      could benefit from effective injury prevention interventions. Our purpose was to
      determine the accuracy of FPTs in identifying adolescent athletes who go on to
      experience lateral ankle sprain(s) and establish specific cutoff scores capable
      of identifying those who sustain a lateral ankle sprain in the near future. Sixty
      four participants (age = 15.5 +/- 1.3 years; height = 161.7 +/- 7.7 cm; mass =
      57.1 +/- 8.4 kg) were recruited from a junior soccer club and tracked for 10
      months. Participants performed the anterior (AN), posterior-medial (PM), and
      posterior-lateral (PL) reach directions of the Star Excursion Balance Test (SEBT)
      and the Single-Leg Hop Test (SLHT) in pre-season, and then were followed for the
      10-month competitive season (12 injured, 52 uninjured). Significant Area Under
      the Curve (AUC) values and cutoff scores were found for the PM (AUC = 0.78; 95%
      CI 0.61-0.95; P = 0.003; Sn = 0.83; Sp = 0.77; cutoff = 76%) and the PL (AUC =
      0.82; 95% CI 0.71-0.94; P = 0.001; Sn = 0.92; Sp = 0.65; cutoff = 70%) reach
      directions of the SEBT and the SLHT (AUC = 0.77; 95% CI 0.60-0.95; P = 0.003; Sn
      = 0.67; Sp = 0.94; cutoff = 15.4 seconds). The PM and PL reach directions of the
      SEBT and the SLHT may be useful as pre-season screening measures to help
      clinicians identify adolescents who will go on to experience a lateral ankle
      sprain.

PMID- 30120832
TI  - A randomised trial of serratus anterior plane block for analgesia after
      thoracoscopic surgery.
AB  - We evaluated the effect of pre-operative serratus anterior plane block on
      postoperative pain and opioid consumption after thoracoscopic surgery. We
      randomly allocated 89 participants to block with 30 ml ropivacaine 0.375% (n =
      44), or no block without placebo or sham procedure (n = 45). We analysed results
      from 42 participants in each group. Serratus anterior plane block reduced mean
      (SD) remifentanil dose during surgery, 0.12 (0.06) mg.h-1 vs. 0.16 (0.06) mg.h-1
      , p = 0.016, and reduced mean (SD) fentanyl consumption in the first 24
      postoperative hours, 3.8 (1.9) MUg.kg-1 vs. 5.7 (1.6) MUg.kg-1 , p = 0.000004.
      Block also reduced the worst median (IQR [range]) pain scores reported in the
      first 24 postoperative hours: 6 (5-7 [3-10]) vs. 7 (6-7 [3-10]), p = 0.027. Block
      decreased dissatisfaction with pain management, categorised as 'highly
      unsatisfactory', 'unsatisfactory', 'neutral', 'satisfactory' or 'highly
      satisfactory': 1/2/21/18/0 vs. 1/14/15/11/1, p = 0.0038. There were no
      differences in the rates of nausea, vomiting, dizziness or length of hospital
      stay. Serratus anterior plane block may be used to reduce pain and opioid use
      after thoracoscopic lung surgery.

PMID- 30120833
TI  - Clinical Usefulness of the Iowa Gambling Task in Severe Alcohol Use Disorders:
      Link with Relapse and Cognitive-Physiological Deficits.
AB  - BACKGROUND: Decision-making impairments have been repeatedly evaluated in severe
      alcohol use disorders (SAUD) using the Iowa Gambling Task (IGT). The IGT,
      capitalizing on strong theoretical background and ecological significance,
      allowed identifying large-scale deficits in this population and is now a standard
      decision-making assessment in therapeutic settings. However, the clinical
      usefulness of the IGT, particularly regarding its ability to predict relapse and
      its link with key cognitive-physiological deficits, remains to be clarified.
      METHODS: Thirty-eight recently detoxified patients with SAUD and 38 matched
      healthy controls performed the IGT, a neuropsychological task using monetary
      rewards to assess decision making under uncertainty and under risk. Disease
      characteristics (e.g., duration and intensity), cognitive abilities,
      psychopathological comorbidities, and physiological damage were also measured, as
      well as relapse rates 6 months later. RESULTS: Compared to controls, patients
      with SAUD presented a dissociation between preserved decision making under
      uncertainty and impaired decision making under risk. In the SAUD group, while
      relapsers (55% of the sample) presented lower global cognitive functioning and
      stronger liver damage than nonrelapsers at detoxification time, no difference was
      found between these subgroups for the IGT. IGT results were not related to
      alcohol-consumption characteristics or cognitive-physiological deficits.
      CONCLUSIONS: SAUD is not related to a global IGT deficit, as suggested earlier,
      but rather to a specific impairment for decision making under risk. This deficit
      is not associated with other disease-related variables and has no relapse
      prediction power. These results question the clinical usefulness of the IGT as a
      tool identifying key treatment levers and guiding (neuro)psychological
      rehabilitation.

PMID- 30120834
TI  - Ethanol (EtOH)-Related Behaviors in alpha-Synuclein Mutant Mice and Association
      of SNCA SNPs with Anxiety in EtOH-Dependent Patients.
AB  - BACKGROUND: Data have shown a role of alpha-synuclein in anxiety and also in
      addiction, particularly in alcohol use disorders (AUD). Since the comorbidity
      between AUD and anxiety is very high and because anxiety is an important factor
      in ethanol (EtOH) relapse, the aim of the present study was to investigate the
      role of alpha-synuclein in moderating EtOH intake, the anxiolytic effects of
      EtOH, and EtOH withdrawal-induced anxiety and convulsions in mice. The study
      aimed to determine whether SNCA variants moderated anxiety in EtOH-dependent
      patients. METHODS: We analyzed the moderator effect of 3 SNCA Tag-single
      nucleotide polymorphisms (Tag-SNPs) rs356200, rs356219, and rs2119787 on the
      anxiety symptoms in 128 EtOH-dependent patients. We used the C57BL/6JOlaHsd Snca
      mutant mice to assess EtOH intake; sensitivity to the anxiolytic effects of EtOH
      in a test battery comprising the open field, the light-dark box, and the elevated
      plus maze; and both anxiety and convulsions induced by EtOH withdrawal. RESULTS:
      Our results demonstrated a reduction in both EtOH intake and preference and also
      a lack of sensitivity to the anxiolytic effects of EtOH in alpha-synuclein mutant
      mice. Results on anxiety-like behavior were mixed, but mutant mice displayed
      increased anxiety when exposed to a low anxiogenic environment. Mutant mice also
      displayed an increase in handling-induced convulsion scores during withdrawal
      after EtOH inhalation, but did not differ in terms of EtOH withdrawal-induced
      anxiety. In humans, we found a significant association of the rs356219 SNP with a
      high level of anxiety (Beck Anxiety Inventory score >15) and the rs356200 SNP
      with a positive familial history of AUD. CONCLUSIONS: Our translational study
      highlights a significant role of alpha-synuclein in components of AUD.

PMID- 30120835
TI  - The "Enseki" sandbath: A novel, safe and effective far-infrared bathing procedure
      for health.
AB  - BACKGROUND: Far-infrared (FIR) is well known with various therapeutic benefits.
      Recently, we have developed a novel FIR bathing system called the Enseki
      sandbath. In this regard, we focused on physical nature of ceramic to radiate FIR
      rays when heated adequately. METHODS: A bathtub was filled with ceramic beads and
      was equipped with computerized system which enabled to supply hot water over the
      ceramic beads and to drain out when beads were sufficiently heated. This system
      was used like sandbathing. Healthy volunteers were laid in bathtubs, covered in
      heated ceramic beads and were bathed for 15 minutes. Microbiological analysis was
      done in samples obtained from the skin surface, ceramic beads, or drained water.
      Furthermore, various physiological parameters were monitored, including blood
      pressure, heart rates, oral temperature, body weight, and blood viscosity. Blood
      samples were simultaneously collected and subjected to biochemical analysis,
      including blood glucose, HbA1c, uric acid, lactate, fatty acid, and others.
      RESULTS: All data showed no physiological overload for tested individuals, and
      any biochemical analysis did not present abnormal score. Bacteriological culture
      grew no pathogens. Results of questionnaires demonstrated that 90% of the
      participants answered the comfort and wished to further repeat the bathing.
      LIMITATIONS: This is a nonrandomized prospective case study. CONCLUSION: We
      concluded that the Enseki method is a safe and well-tolerated FIR bathing
      procedure for regeneration and relaxation.

PMID- 30120836
TI  - Bone Effects of Binge Alcohol Drinking Using Prepubescent Pigs as a Model.
AB  - BACKGROUND: Although chronic alcohol consumption in adults is an established risk
      factor for osteoporotic fractures, there is a huge gap in our knowledge about
      bone effects of binge drinking in adolescents. The aim of this pilot study was
      therefore to assess skeletal effects of binge alcohol drinking using prepubescent
      pigs as a large animal model. METHODS: Piglets aged 2 months were offered alcohol
      orally as a mixture of hard liquor and apple juice. Those with the highest
      propensity to drink alcohol were included in the experiment and received 1.4 g
      alcohol/kg bodyweight 2 times per week for 2 months (alcohol group); control
      piglets received apple juice in an identical manner. At the age of 4 months, the
      animals were euthanized; trabecular and cortical bone samples from the femur, the
      tibia, the humerus, and the fourth vertebral body harvested during necropsy were
      assessed by microcomputed tomography and dynamic histomorphometry. In addition,
      blood chemistry and blood alcohol determinations were performed. RESULTS: Blood
      alcohol levels assessed 1 hour after alcohol administration were 0.990/00 +/-
      0.15, 1.120/00 +/- 0.2, and 1.140/00 +/- 0.18 at the ages of 2, 3, and 4 months,
      respectively. In the alcohol group, serum calcium and phosphate levels were
      decreased. In the femur, trabecular number and connectivity density were lower in
      the alcohol than in the control group, and in the humerus and the fourth
      vertebral bodies, an opposite pattern was seen for trabecular number and
      connectivity density, respectively. Cortical density was higher in the humerus
      and trabecular density higher in the tibia of the alcohol group compared to the
      control group. Cortical porosity was lower in the humerus of the alcohol group.
      No significant differences were seen for trabecular thickness, trabecular
      separation, bone volume fraction, and static and dynamic histomorphometric
      parameters. CONCLUSIONS: In this pilot study, we have assessed skeletal effects
      of binge alcohol drinking by using prepubescent pigs as a promising large animal
      model. Binge drinking has bone effects that are site-specific. However, these
      data have to be verified in a larger study population.

PMID- 30120837
TI  - Comparative analysis of immune cell subsets in peripheral blood from patients
      with periodontal disease and healthy controls.
AB  - Periodontitis is a chronic inflammatory disease caused by the colonization of
      teeth by the bacterial plaque biofilm and the resultant host immune responses in
      adjacent periodontal tissues. Disease severity can vary dramatically between
      patients with periodontitis, with some subjects displaying inflammation without
      bony destruction (gingivitis), while others experience chronic progressive or
      rapidly aggressive gingival connective tissue damage and bone loss. To determine
      whether peripheral immune dysregulation is associated with periodontitis, we
      performed extensive analysis of immune cell subsets in peripheral blood from
      patients with chronic or aggressive periodontitis versus periodontally healthy
      control subjects. Peripheral blood mononuclear cells (PBMC) from patients with
      chronic periodontitis or aggressive periodontitis and from periodontally healthy
      controls were analysed by 8-10-colour flow cytometry for the frequencies of
      various lymphocyte subsets, including interleukin (IL)-17-, interferon (IFN)
      gamma-, tumour necrosis factor (TNF)-alpha- and IL-10-producing cells, and the
      frequencies and phenotype of monocytes. Cytokine levels in serum from the
      different groups were determined by Luminex assay. We found no significant
      differences in the frequencies of major immune cell populations [CD4+ T cells,
      CD8+ T cells, gammadelta T cells, CD4+ CD45RO+ CD25+ CD127low regulatory T cells
      (Tregs ), CD19+ B cells, CD14+ monocytes] or of cytokine-producing T cells, or in
      the phenotype of CD14+ monocytes in peripheral blood from these patient cohorts.
      Additionally, no significant differences were observed in serum levels of
      prototypical inflammatory cytokines. These results suggest that the local
      gingival inflammatory response is not reflected by obvious changes in major blood
      immune cell subset frequencies.

PMID- 30120838
TI  - Hamstring and other thigh injuries in children and young athletes.
AB  - BACKGROUND: In adults, hamstring injuries may lead to long periods of
      rehabilitation and carry a definite risk of recurrence. However, no studies
      detail how these injuries affect young athletes. OBJECTIVE: To describe and
      analyze injuries in the hamstring area in young athletes. To identify risk
      factors for injuries to the hamstring area in this age group, which will make it
      possible to design and optimize prevention plans. METHODS: The study population
      consisted of 1157 young athletes with an average age of 13.56 years, all members
      of the Barcelona Football Club. Injuries to the hamstring area over three
      consecutive seasons (from July 2007 to June 2010) were analyzed. RESULTS: The 50
      injuries in the hamstring muscle complex included 14 injuries to the biceps
      femoris, 17 to the semitendinosus-semimembranosus complex, 10 cases of delayed
      onset muscle soreness (DOMS), and nine avulsion of the ischial tuberosity.
      Hamstring injuries were first identified in young athletes starting from age
      nine, with an age-related increased rate up to the age of 15, and a lower
      incidence at age 14, 16, and 18. The average time lost following an hamstring
      injury was 21 days and 43.4 days following avulsion from the ischium. The highest
      incidence of injuries occurred in football players. CONCLUSIONS: Hamstring
      injuries in this group of young athletes are less prevalent than in adults.

PMID- 30120839
TI  - Development of a methodology to combine fMRI and EMG to measure emotional
      responses in patients with anorexia nervosa.
AB  - OBJECTIVE: Individuals with eating disorders are theorized to have basic
      impairments in affective appraisal and social-emotional processing that
      contribute to pathogenesis of the disease. We aimed to determine if facial
      electromyography could be used to discriminate between happy and disgust emotions
      during simultaneous acquisition of an fMRI BOLD sequence in efforts to establish
      a novel tool for investigating emotion-driven hypotheses about eating pathology.
      In line with standards for rigor and reproducibility, we provide detailed
      protocols and code to support each step of this project. METHOD: Sixteen
      adolescents with low-weight eating disorders viewed emotional faces (Happy or
      Disgust) and were asked to mimic their facial expression during simultaneous BOLD
      and EMG (Corrugator supercilli, Lavator lavii, Zygomaticus major) acquisition.
      Trials were repeated with the scanner off and again with scanner on (i.e.,
      fatigue). RESULTS: The Levator and Zygomaticus activation patterns discriminated
      disgust and happy faces successfully. The pattern held between scanner on and off
      conditions, but muscle activation attenuated in the Fatigue condition, especially
      for the Zygomaticus. DISCUSSION: Simultaneous fMRI-EMG is a new tool capable of
      discriminating specific emotions based on muscle activation patterns and can be
      leveraged to answer emotion-driven hypotheses about clinical populations
      characterized by difficulty labeling or processing emotions.

PMID- 30120840
TI  - Expression and localization of follicle-stimulating hormone receptor in the yak
      uterus during different stages of the oestrous cycle.
AB  - Morphological changes of the uterus and alterations in its secretory activity
      under the influence of steroid hormones been well documented. The oestrous cycle
      is also associated with significant changes in plasma follicle-stimulating
      hormone (FSH), whose effects are mediated through its receptor (FSHR). Reports
      showed that in many mammals, FSHR was expressed in gonadal and extragonadal
      tissues including cervix, female reproductive tract, and pituitary gland.
      Follicle-stimulating hormone (FSH) signals through endothelial FSHR directly
      stimulate angiogenesis and involved in the timing of birth in human, and the
      presence of FSHR in the placenta is essential for normal pregnancy in mice. But
      little is known about FSHR expression in the yak uterus. The main objective of
      the present study was to determine the expression and localization of FSHR in the
      yak uterus during different phases of the oestrous cycle. Results showed that
      FSHR protein was localized in the surface and glandular epithelial cells, stroma
      cells, myometrial smooth muscle cells and blood vessel endothelial cells. The
      expression of FSHR protein peaked at oestrus, significantly decreased at
      dioestrus (p < 0.05) and increased again at proestrus. FSHR mRNA was highly
      expressed at both proestrus and oestrus, and decreased at metestrus with the
      lowest values at dioestrus (p < 0.05). In conclusion, FSHR expression in the yak
      uterus changed with the stage of the oestrous cycle suggesting that FSHR plays an
      essential role in regulating the endometrial and myometrial functions during the
      oestrus cycle in the yak.

PMID- 30120841
TI  - Tenofovir Alafenamide for the Treatment of Chronic Hepatitis B Monoinfection.
AB  - Tenofovir alafenamide (TAF) is indicated for adult patients with chronic
      hepatitis B virus (HBV) infection with compensated liver disease at an oral dose
      of 25 mg/day. TAF is a more stable prodrug in the plasma than tenofovir
      disoproxil fumarate (TDF), leading to decreased plasma exposure of tenofovir.
      Decreased exposure is thought to reduce the risk of long-term TDF toxicities,
      such as nephrotoxicity and decreased bone mineral density (BMD). TAF, a
      nucleotide reverse transcriptase inhibitor, has the same mechanism of action as
      TDF. The results of phase III primary trials and extensions showed that TAF is
      noninferior to TDF at suppressing the HBV viral load in treatment-naive and
      treatment-experienced HBeAg-negative and HBeAg-positive patients at 48 weeks, 96
      weeks, and 144 weeks of therapy. The most commonly reported adverse events were
      headache, abdominal pain, fatigue, cough, nausea, and back pain. At all evaluated
      time points (out to 144 wks of treatment), patients who received TAF had less
      risk of nephrotoxicity and less of a decline in BMD than the patients who
      received TDF. TAF appears to be safe in patients with a creatinine clearance
      (Clcr ) above 15 ml/min; however, TAF is not currently recommended in patients
      with an estimated Clcr below this threshold. TAF is safe in patients with mild
      hepatic impairment but is not currently recommended in patients with moderate or
      severe hepatic impairment (Child-Pugh class B or C).

PMID- 30120842
TI  - Drug treatments associated with Achilles tendon rupture. A case-control study
      involving 1118 Achilles tendon ruptures.
AB  - The incidence of Achilles tendon (AT) rupture, especially nonsport-related
      rupture, is increasing, while the reasons for this increase are largely unknown.
      The association between the AT rupture and the use of various drug treatments was
      studied. We collected AT rupture patients from the Finnish Hospital Discharge
      Register. We also acquired information about all the doctor-prescribed drugs they
      had purchased within 1 year before the rupture. For comparison, we randomly
      selected age- and sex-matched controls from the Finnish Population Register.
      There were 1118 AT rupture patients. Several drug groups had a statistically
      significant association with the AT rupture. Our study confirmed an association
      between fluoroquinolone antibiotics and AT rupture (OR 2.20, P = 0.005). A
      statistically significant association of renin-angiotensin II receptor
      antagonists with tendon rupture (OR 7.59, P = 0.003) was a previously unreported
      finding. The increasing incidence of AT rupture, especially in middle-aged and
      elderly patients, might partially be a consequence of the increased use of
      certain drug treatments. Some associations are probably explained by the
      symptomatic treatment of the painful tendon before the rupture.

PMID- 30120843
TI  - Ascorbic acid-cyclodextrin complex alters the expression of genes associated with
      lipid metabolism in in vitro produced bovine embryos.
AB  - Ascorbic acid (AC) used as antioxidant in embryo culture is very sensitive and
      degrades unavoidably in aqueous solution. Methyl beta-cyclodextrin (CD) improved
      the stability of AC in solution to elevated temperature, light, humidity, and
      oxidation. The aim of this study was to evaluate the effect of the complex AC-CD
      during in vitro maturation (IVM) or in vitro culture (IVC) on oocyte
      developmental competence and subsequent embryo development and quality. AC-CD
      (100 MUM) was added to IVM media and maturation level and embryo development were
      examined. Matured oocytes, their cumulus cells, and produced blastocysts were
      snap-frozen for gene expression analysis by RT-qPCR. Besides, in vitro produced
      zygotes were cultured with 100 MUM of AC-CD and blastocysts were as well snap
      frozen for gene expression analysis. A group without AC-CD (control- ) and other
      with CD (control+ ) were included. No differences were found on maturation,
      cleavage or blastocyst rates. However, in matured oocytes, AC-CD down-regulated
      BAX, GPX1, and BMP15. In cumulus cells, AC-CD down-regulated BAX/BCL2 and GSTA4
      while upregulated BCL2 and CYP51A1. The expression of SL2A1, FADS1, PNPLA, and
      MTORC1 was down-regulated in blastocysts derived from oocytes matured with AC-CD,
      while in blastocysts derived from zygote cultured with AC-CD, CYP51A1 and IGF2R
      was down-regulated and PNPLA2 up-regulated. In conclusion, AC-CD in both IVM and
      IVC media may reduce accumulated fat by increasing lipolysis and suppressing
      lipogenesis in blastocysts derived from both oocytes and zygotes cultured with AC
      CD, suggesting that CD improves the quality of embryos and bioavailability of AC
      during IVM and IVC. This article is protected by copyright. All rights reserved.

PMID- 30120844
TI  - Impact of Serum Cystatin C-Based Glomerular Filtration Rate Estimates on Drug
      Dose Selection in Hospitalized Patients.
AB  - STUDY OBJECTIVE: Serum creatinine (Sc r ) concentration is used to calculate
      estimated glomerular filtration rate (eGFR) for medication dosing. Serum cystatin
      C (CysC) concentration has been proposed as an adjunct or alternative to Scr .
      This study sought to evaluate the possible impact of using CysC in eGFR equations
      on drug dose recommendations in hospitalized patients with infections. DESIGN:
      Retrospective analysis of prospectively collected data. SETTING: Large academic
      tertiary care medical center. PATIENTS: A total of 308 adults with suspected or
      documented infections and stable kidney function who were hospitalized between
      2012 and 2015. MEASUREMENTS AND MAIN RESULTS: Standardized Sc r and CysC measured
      at the time of antibiotic dosing were used to estimate GFR from the three Chronic
      Kidney Disease Epidemiology Collaborative (CKD-EPI) equations using Sc r (eGFRCr
      ), CysC(eGFRCysC ), or a combination of Sc r and CysC (eGFRCr-CysC ), and these
      values were compared with estimated creatinine clearance (eClcr ) from the
      Cockcroft-Gault equation (standard of care for drug dosage adjustments). The
      eGFRs were categorized into five common dosage adjustment strata (lower than 20,
      20-49, 50-79, 80-130, and higher than 130 ml/min), and agreement between
      equations was tested with the weighted kappa statistic. Recommended drug doses
      varied considerably between the eClcr and the CKD-EPI equations (weighted kappa
      [95% confidence interval]: eGFRCr 0.73 [0.68-0.79], eGFRCysC 0.42 [0.35-0.5],
      eGFRCr-CysC 0.65 [0.6-0.71]). If eGFRCr, eGFRCysC , or eGFRCr-CysC were used
      instead of eClcr to dose drugs, 11%, 12%, and 8% of doses, respectively, would be
      higher, and 12%, 38%, and 24% of doses, respectively, would be lower. CONCLUSION:
      Significant discordance in drug doses was observed when the CKD-EPI equations
      were used in place of eClcr . When CysC was included in eGFR equations,
      recommended doses were often lower. Further study is needed to develop and test
      drug-specific dosing guidelines that incorporate alternate renal biomarkers
      and/or more contemporary eGFR equations.

PMID- 30120845
TI  - Skeletal muscle interstitial O2 pressures: bridging the gap between the capillary
      and myocyte.
AB  - The oxygen transport pathway from air to mitochondria involves a series of
      transfer steps within closely integrated systems (pulmonary, cardiovascular, and
      tissue metabolic). Small and finite O2 stores in most mammalian species require
      exquisitely controlled changes in O2 flux rates to support elevated ATP turnover.
      This is especially true for the contracting skeletal muscle where O2 requirements
      may increase two orders of magnitude above rest. This brief review focuses on the
      mechanistic bases for increased microvascular blood-myocyte O2 flux (VO2 ) from
      rest to contractions. Fick's law dictates that VO2 elevations driven by muscle
      contractions are produced by commensurate changes in driving force (ie, O2
      pressure gradients; DeltaPO2 ) and/or effective diffusing capacity (DO2 ). While
      previous evidence indicates that increased DO2 helps modulate contracting muscle
      O2 flux, up until recently the role of the dynamic DeltaPO2 across the capillary
      wall was unknown. Recent phosphorescence quenching investigations of both
      microvascular and novel interstitial PO2 kinetics in health have resolved an
      important step in the O2 cascade between the capillary and myocyte. Specifically,
      the significant transmural DeltaPO2 at rest was sustained (but not increased)
      during submaximal contractions. This supports the contention that the blood
      myocyte interface provides a substantial effective resistance to O2 diffusion and
      underscores that modulations in erythrocyte hemodynamics and distribution (DO2 )
      are crucial to preserve the driving force for O2 flux across the capillary wall
      (DeltaPO2 ) during contractions. Investigation of the O2 transport pathway close
      to muscle mitochondria is key to identifying disease mechanisms and develop
      therapeutic approaches to ameliorate dysfunction and exercise intolerance.

PMID- 30120846
TI  - The neural basis of motivational influences on cognitive control.
AB  - Cognitive control mechanisms support the deliberate regulation of thought and
      behavior based on current goals. Recent work suggests that motivational
      incentives improve cognitive control and has begun to elucidate critical neural
      substrates. We conducted a quantitative meta-analysis of neuroimaging studies of
      motivated cognitive control using activation likelihood estimation (ALE) and
      Neurosynth to delineate the brain regions that are consistently activated across
      studies. The analysis included studies that investigated changes in brain
      activation during cognitive control tasks when reward incentives were present
      versus absent. The ALE analysis revealed consistent recruitment in regions
      associated with the frontoparietal control network including the inferior frontal
      sulcus and intraparietal sulcus, as well as regions associated with the salience
      network including the anterior insula and anterior mid-cingulate cortex. As a
      complementary analysis, we performed a large-scale exploratory meta-analysis
      using Neurosynth to identify regions that are recruited in studies using of the
      terms cognitive control and incentive. This analysis replicated the ALE results
      and also identified the rostrolateral prefrontal cortex, caudate nucleus, nucleus
      accumbens, medial thalamus, inferior frontal junction, premotor cortex, and
      hippocampus. Finally, we separately compared recruitment during cue and target
      periods, which tap into proactive engagement of rule-outcome associations, and
      the mobilization of appropriate viscero-motor states to execute a response,
      respectively. We found that largely distinct sets of brain regions are recruited
      during cue and target periods. Altogether, these findings suggest that flexible
      interactions between frontoparietal, salience, and dopaminergic midbrain-striatal
      networks may allow control demands to be precisely tailored based on expected
      value.

PMID- 30120848
TI  - CRISPR/Cas9-mediated disruption of the immediate early-0 and 2 as a therapeutic
      approach to Bombyx mori nucleopolyhedrovirus in transgenic silkworm.
AB  - The CRISPR/Cas9 system is a powerful tool for the treatment of infectious
      diseases. In our previous study, we knocked out the Bombyx mori
      nucleopolyhedrovirus (BmNPV) key genes and BmNPV-dependent host factor to
      generate transgenic antiviral strains. To further expand the range of target
      genes for BmNPV and more effectively prevent and control pathogenic infections,
      we performed gene editing and antiviral analysis by constructing a target
      directed baculovirus early transcriptional activator immediate early-0 (ie-0) and
      2 (ie-2) transgenic silkworm line. We hybridized it with Cas9 transgenic line to
      produce a double-positive transgenic Cas9(+)/sgIE0-sgIE2(+) line that could
      activate the CRISPR gene editing system. We first demonstrated that the system is
      capable of efficiently editing target genes and resulting in fragment deletions
      in the BmNPV genome. Survival rate of the transgenic Cas9(+)/sgIE0-sgIE2(+) line
      reached 65% after inoculation with 1 * 106 occlusion bodies/larva. Molecular
      analysis showed that BmNPV DNA replication and viral gene expression level in the
      transgenic Cas9(+)/sgIE0-sgIE2(+) line were significantly inhibited compared with
      the control Cas9(-)/sgIE0-sgIE2(-) line. These results indicated that IE-0 and IE
      2, as baculovirus early transcriptional activators, can be used as target sites
      for gene therapy and that multigene editing could expand the range of target
      sites for research to create silkworm resistance breeds.

PMID- 30120847
TI  - Neural representation of word categories is distinct in the temporal lobe: An
      activation likelihood analysis.
AB  - The distinction between nouns and verbs is a language universal. Yet, functional
      neuroimaging studies comparing noun and verb processing have yielded inconsistent
      findings, ranging from a complete frontal(verb)-temporal(noun) dichotomy to a
      complete overlap in activation patterns. The current study addressed the debate
      about neural distinctions between nouns and verbs by conducting an activation
      likelihood estimation (ALE) meta-analysis of probabilistic cytoarchitectonic
      maps. Two levels of analysis were conducted: simple effects (Verbs vs. Baseline,
      Nouns vs. Baseline), and direct comparisons (Verbs vs. Nouns, Nouns vs. Verbs).
      Nouns were uniquely associated with a left medial temporal cluster (BA37).
      Activation foci for verbs included extensive inferior frontal (BA44-47) and mid
      temporal (BA22, 21) regions in the left hemisphere. These findings confirm that
      the two grammatical classes have distinct neural architecture in supra-modal
      brain regions. Further, nouns and verbs overlapped in a small left lateral
      inferior temporal activation cluster (BA37), which is a region for modality
      independent, grammatical class-independent lexical representations. These
      findings are most consistent with the view that as one acquires language,
      linguistic representations for a lexical category shift from the modality
      specific cortices which represent prototypical members of that category (e.g.,
      motion for verbs) to abstract amodal representations in close proximity to
      modality specific cortices.

PMID- 30120849
TI  - Reducing stress and burnout in the public-sector work environment: A mindfulness
      meditation pilot study.
AB  - ISSUE ADDRESSED: Identifying ways to manage the psychological and emotional costs
      of workplace stress is essential. Mindfulness meditation is reported to support
      mental well-being; however, findings are limited in Australian business settings.
      Accordingly, this study explored the efficacy of a mindfulness meditation program
      tailored for an Australian public-sector workplace. METHODS: A mixed-methods,
      single-group, pre-/post-test design was used to evaluate a proof-of-concept
      mindfulness intervention. Quantitative measures included the Perceived Stress
      Scale and Maslach Burnout Inventory. Survey data were collected to analyse
      participant experiences. Participants (n = 65) were recruited from a government
      organisation. The 8-week program ran weekly for 45 minutes and had a 65%
      retention rate. Resources were provided to support home practice. RESULTS:
      Statistically significant decreases were obtained for perceived stress (d = 0.8)
      and emotional exhaustion (d = 0.4). Themes from qualitative findings suggested
      participants experienced an increased recognition of stress triggers, increased
      ability to detach from stressors, increased calmness and increased ability to
      prioritise work. CONCLUSIONS: Qualitative results extend comparable quantitative
      research by detailing how an appropriately tailored 8-week meditation-based
      program has the potential to decrease perceived stress in highly stressful work
      environments. SO WHAT?: Triangulated data suggest that an appropriately adapted
      mindfulness meditation program can be an effective, efficient and low-cost
      inclusion within an organisation's health promotion repertoire to help increase
      mental health among staff.

PMID- 30120850
TI  - Expression of TGFBR1, TGFBR2, TGFBR3, ACVR1B and ACVR2B is altered in ovaries of
      cows with cystic ovarian disease.
AB  - The objective of the present study was to examine the expression of transforming
      growth factor beta receptor (TGFBR)1, TGFBR2, TGFBR3, Activin Receptor (ACVR)1B
      and ACVR2B in ovaries of cows with Cystic Ovarian Disease (COD). The expression
      of the selected receptors was determined by immunohistochemistry in sections of
      ovaries from cows with ACTH-induced and spontaneous COD. Expression of TGFBR1 and
      TGFBR3 was higher in granulosa cells of cysts from cows with spontaneous COD than
      in tertiary follicles from the control group. Additionally, TGFBR3 expression was
      higher in granulosa cells of cysts from cows with ACTH-induced COD than in those
      from the control group and lower in theca cells of spontaneous and ACTH-induced
      cysts than in tertiary control follicles. There were no changes in the expression
      of TGFBR2. ACVR1B expression was higher in granulosa cells of tertiary follicles
      of cows with spontaneous COD than in the control group, whereas ACVR2B expression
      was higher in cysts of the spontaneous COD group than in tertiary follicles from
      the control group. The alterations here detected, together with the altered
      expression of the ligands previously reported, indicate alterations in the
      response of the ligands in the target cells, modifying their actions at cellular
      level. This article is protected by copyright. All rights reserved.

PMID- 30120851
TI  - Test-retest reliability of a stimulation-locked evoked response to deep brain
      stimulation in subcallosal cingulate for treatment resistant depression.
AB  - Deep brain stimulation (DBS) to the subcallosal cingulate cortex (SCC) is an
      emerging therapy for treatment resistant depression. Precision targeting of
      specific white matter fibers is now central to the model of SCC DBS treatment
      efficacy. A method to confirm SCC DBS target engagement is needed to reduce
      procedural variance across treatment providers and to optimize DBS parameters for
      individual patients. We examined the reliability of a novel cortical evoked
      response that is time-locked to a 2 Hz DBS pulse and shows the propagation of
      signal from the DBS target. The evoked response was detected in four individuals
      as a stereotyped series of components within 150 ms of a 6 V DBS pulse, each
      showing coherent topography on the head surface. Test-retest reliability across
      four repeated measures over 14 months met or exceeded standards for valid test
      construction in three of four patients. Several observations in this pilot sample
      demonstrate the prospective utility of this method to confirm surgical target
      engagement and instruct parameter selection. The topography of an orbital frontal
      component on the head surface showed specificity for patterns of forceps minor
      activation, which may provide a means to confirm DBS location with respect to key
      white matter structures. A divergent cortical response to unilateral stimulation
      of left (vs. right) hemisphere underscores the need for feedback acuity on the
      level of a single electrode, despite bilateral presentation of therapeutic
      stimulation. Results demonstrate viability of this method to explore patient
      specific cortical responsivity to DBS for brain-circuit pathologies.

PMID- 30120852
TI  - Characterization of mutation spectrum and identification of novel mutations in
      ATP7B gene from a cohort of Wilson disease patients: Functional and therapeutic
      implications.
AB  - Wilson disease (WD), a copper metabolism disorder, occurs due to the presence of
      mutations in the gene encoding ATP7B, a protein that primarily facilitates
      hepatic copper excretion. A better understanding of spectrum and functional
      significance of ATP7B variants is critical to formulating targeted and
      personalized therapies. Henceforth, we screened and sequenced 21 exons of ATP7B
      gene from 50 WD patients and 60 healthy subjects. We identified 28 variants
      comprising, seven novels in 20% alleles, while eight variations affecting 23%
      alleles were first time reported in Indian cohort. The c.813C>A, p.(Cys271*)
      (10%) was the most frequent mutation. Bioinformatics analysis revealed five of
      seven novel variants viz. c.1600C>A, p.(Pro534Thr); c.1616C>A, p.(Pro539His);
      c.1924G>T, p.(Asp642Tyr); c.2168G>C, p.(Arg723Thr); c.2174G>C, p.(Arg725Thr)
      resulted in protein misfolding. Sequence conservation analysis of ATP7B regions
      containing novel variants documented an evolutionarily conserved nature.
      Functional analysis of these novel variants in five different cell lines lacking
      inherent ATP7B expression demonstrated sensitivity to CuCl2 -treatment,
      experiencing augmented cellular copper retention and decreased copper excretion
      as well as ceruloplasmin secretion to that of wildtype-ATP7B expressing cells.
      Interestingly, pharmacological chaperone 4-phenylbutyrate, a clinically approved
      compound, partially restored protein function of ATP7B mutants. These findings
      might enable novel treatment strategies in WD by clinically enhancing the protein
      expression of mutant ATP7B with residual copper export activity.

PMID- 30120853
TI  - Epithelial-mesenchymal transition and microRNAs: Challenges and future
      perspectives in oral cancer.
AB  - BACKGROUND: Head and neck cancer is the sixth most common cancer worldwide, with
      oral squamous cell carcinoma (OSCC) being the most representative type. OSCC is a
      public health problem with high morbidity and poor survival rate. Epithelial
      mesenchymal transition is emerging as a hallmark in OSCC. METHODS: In this study,
      we described the role of microRNAs in epithelial-mesenchymal transition
      regulation in OSCC based on a PubMed search using articles published in English
      between January 1, 2010, and January 31, 2018. RESULTS: MicroRNA's regulatory
      networks seem to be a hallmark of epithelial-mesenchymal transition in OSCC
      pathophysiology becoming a growing challenge to design new studies and strategies
      from biology to clinical applications. CONCLUSION: Therefore, we propose that
      targeting therapies to epithelial-mesenchymal transition-type cells, namely,
      coordinating microRNAs and/or hydrophobic drugs, such as conventional therapy,
      could be a promising strategy to improve the outcomes of patients with OSCC.

PMID- 30120854
TI  - Singing in the brain: Neural representation of music and voice as revealed by
      fMRI.
AB  - The ubiquity of music across cultures as a means of emotional expression, and its
      proposed evolutionary relation to speech, motivated researchers to attempt a
      characterization of its neural representation. Several neuroimaging studies have
      reported that specific regions in the anterior temporal lobe respond more
      strongly to music than to other auditory stimuli, including spoken voice.
      Nonetheless, because most studies have employed instrumental music, which has
      important acoustic distinctions from human voice, questions still exist as to the
      specificity of the observed "music-preferred" areas. Here, we sought to address
      this issue by testing 24 healthy young adults with fast, high-resolution fMRI, to
      record neural responses to a large and varied set of musical stimuli, which,
      critically, included a capella singing, as well as purely instrumental excerpts.
      Our results confirmed that music; vocal or instrumental, preferentially engaged
      regions in the superior STG, particularly in the anterior planum polare,
      bilaterally. In contrast, human voice, either spoken or sung, activated more
      strongly a large area along the superior temporal sulcus. Findings were
      consistent between univariate and multivariate analyses, as well as with the use
      of a "silent" sparse acquisition sequence that minimizes any potential influence
      of scanner noise on the resulting activations. Activity in music-preferred
      regions could not be accounted for by any basic acoustic parameter tested,
      suggesting these areas integrate, likely in a nonlinear fashion, a combination of
      acoustic attributes that, together, result in the perceived musicality of the
      stimuli, consistent with proposed hierarchical processing of complex auditory
      information within the temporal lobes.

PMID- 30120855
TI  - Mast cells and primary systemic vasculitides.
AB  - Vasculitides are characterized by inflammation and necrosis of blood vessels
      leading to vessel occlusion and ischemic damages of tissues. Among the
      inflammatory cells involved in vasculitides, neutrophils, T cells, and
      macrophages have been identified as the predominant cell type. This review
      article is focused on the role of mast cells in these chronic inflammatory
      processes. Mast cells are characterized by their complex plasticity. Increasing
      evidences document that mast cells exert both pro- and anti-inflammatory
      functions depending on the cell types and the microenvironment they reside in. In
      this context, mast cell mediators able to modulate progression of vasculitides at
      different levels and the anatomic localization of mast cells in different
      vasculitides will be described. Finally, therapeutic approach including
      inhibition of recruitment of mast cells to the inflammatory infiltrate and
      blockade of their proinflammatory effects and proangiogenic functions as
      potential new targets for the treatment of these diseases will be discussed.

PMID- 30120857
TI  - Mitral cells and the glucagon-like peptide 1 receptor: The sweet smell of
      success?
AB  - The olfactory bulb (OB) is often affected at very early stages of
      neurodegenerative disorders, in the so-called "prodromal" phase. In Parkinson's
      disease (PD), olfactory disturbances appear years before motor symptoms arise.
      Additionally, pathological alpha-synuclein aggregates are found in olfactory
      regions before spreading to other areas of the brain. Being positioned at the
      frontier between the brain and a potentially hostile environment, could explain
      the particular vulnerability of the OB. Mitral cells (MCs), the principal
      projecting neurons of the olfactory system, are involved in the pathogenesis and
      in the prion-like progression of PD. They are affected by Lewy pathology and are
      thought to contribute to the axonal transport of misfolded alpha-synuclein to
      other regions of the brain. Here, we first describe the main markers reported to
      distinguish MCs from other olfactory neurons. We focus on the glucagon-like
      peptide 1 receptor (GLP-1R), a membrane protein specifically expressed in MCs.
      After summarizing OB pathology, we explore the idea of targeting specifically MCs
      with GLP-1 or its analogues. Exenatide has shown great promise as a
      neuroprotective and neurorestorative agent and has been used in a clinical trial
      for clinical PD. Since GLP-1R activation has the ability to mitigate many facets
      of prodromal PD pathology, we postulate that once a robust biomarker is in place
      that is capable of identifying individuals in the prodromal phase of PD, homing
      in on GLP-1R could assist in deferring, or eradicating to a significant degree,
      the clinical manifestation of this debilitating human disorder.

PMID- 30120856
TI  - Use of VHH antibodies for the development of antigen detection test for visceral
      leishmaniasis.
AB  - We have recently developed a sensitive and specific urine-based antigen detection
      ELISA for the diagnosis of visceral leishmaniasis (VL). This assay used rabbit
      IgG and chicken IgY polyclonal antibodies specific for the Leishmania infantum
      proteins iron superoxide dismutase 1 (Li-isd1), tryparedoxin1 (Li-txn1) and
      nuclear transport factor 2 (Li-ntf2). However, polyclonal antibodies have
      limitations for upscaling and continuous supply. To circumvent these hurdles, we
      began to develop immortalized monoclonal antibodies. We opted for recombinant
      camelid VHHs because the technology for their production is well established and
      they do not have Fc, hence providing less ELISA background noise. We report here
      an assay development using VHHs specific for Li-isd1 and Li-ntf2. This new assay
      was specific and had analytical sensitivity of 15-45 pg/mL of urine. The clinical
      sensitivity was comparable to that obtained with the ELISA assembled with
      conventional rabbit and chicken antibodies to detect these two antigens.
      Therefore, similar to our former studies with conventional antibodies, the future
      inclusion of VHH specific for Li-txn1 and/or other antigens should further
      increase the sensitivity of the assay. These results confirm that immortalized
      VHHs can replace conventional antibodies for the development of an accurate and
      reproducible antigen detection diagnostic test for VL.

PMID- 30120858
TI  - Current and Investigational Agents Targeting the Phosphoinositide 3-Kinase
      Pathway.
AB  - Prevalent molecular alterations of the phosphoinositide 3-kinase (PI3K) pathway
      are found on solid tumors and are expressed in leukocytes, making it a desirable
      target in both solid and hematologic malignancies. In recent years, two agents
      targeting this pathway have been approved by the United States Food and Drug
      Administration, idelalisib and copanlisib, with many others under investigation.
      Due to the off-target effects seen with these agents, those under development
      have varying isoform specificity that mitigates toxicity. In this review, we
      attempt to illustrate the varying differences among these agents, both
      mechanistically as well as highlight differences in their respective adverse
      effect profiles.

PMID- 30120859
TI  - Differences in motor network dynamics during recovery between supra- and infra
      tentorial ischemic strokes.
AB  - Most previous stroke studies have been performed in heterogeneous patient
      populations. Moreover, the brain network might demonstrate different recovery
      dynamics according to lesion location. In this study, we investigated variation
      in motor network alterations according to lesion location. Forty patients with
      subcortical ischemic stroke were enrolled. Patients were divided into two groups:
      21 patients with supratentorial stroke (STS) and 19 patients with infratentorial
      stroke (ITS). All patients underwent resting-state functional magnetic resonance
      imaging and behavioral assessment at 2 weeks and 3 months poststroke. Twenty-four
      healthy subjects participated as a control group. To compare altered connectivity
      between groups, measures used in previous studies to evaluate interhemispheric
      balance and global network reorganization were investigated and the relationship
      between network measures and motor functions were examined. Cortico-cerebellar
      connectivity was also extracted to investigate its relationship with
      interhemispheric connectivity. In the STS group, measures related to
      interhemispheric balance were disrupted compared to the control group 2 weeks
      poststroke, while this was not found in the ITS group. During recovery, measures
      related to global network reorganization in the STS group and measures related to
      interhemispheric balance in the ITS group demonstrated significant changes,
      respectively. Moreover, motor functions were correlated with altered network
      measures in both groups. There was an interactive relationship between cortico
      cerebellar and interhemispheric cortical connectivity only in the ITS group.
      Different changes in the motor network were observed depending on the location of
      stroke lesions. These results might originate from differences in the
      interactions between cortico-cerebellar and interhemispheric connectivity.

PMID- 30120860
TI  - LncRNA-FENDRR mediates VEGFA to promote the apoptosis of brain microvascular
      endothelial cells via regulating miR-126 in mice with hypertensive intracerebral
      hemorrhage.
AB  - BACKGROUND: LncRNA-FENDRR is a kind of endothelial genes critical for vascular
      development. Moreover, miR-126 and vascular endothelial growth factor A (VEGFA)
      are also involved in the physiological process of vascular endothelial cells.
      This study aimed to the underlying mechanism of FENDRR involving miR-126 and
      VEGFA in hypertensive intracerebral hemorrhage (HICH). METHODS: C57BL/6 mice were
      chosen to establish HICH model. The expression of FENDRR, miR-126, and VEGFA at
      mRNA level was determined by qRT-PCR. The protein expression of VEGFA was
      assessed using Western blot. RIP assay and RNA pull-down assay were used to the
      relationship between FENDRR and miR-126. Flow cytometry was used to analyze cell
      apoptosis. RESULTS: The levels of FENDRR and VEGFA were increased, and miR-126
      expression was decreased in vascular endothelial cells (VECs) from the right
      brain of model mice and human brain microvascular endothelial cells (HBMECs)
      treated by thrombin. Overexpression of FENDRR promoted the apoptosis of HBMECs.
      FENDRR regulating VEGFA participated in HBMECs apoptosis through targeting miR
      126. Downregulation of FENDRR was indicated to relieve the HICH in mice.
      CONCLUSIONS: FENDRR could promote the apoptosis of HBMECs via miR-126 regulating
      VEGFA in HICH.

PMID- 30120861
TI  - FOXM1 overexpression is associated with adverse outcome and predicts response to
      intravesical instillation therapy in stage pT1 non-muscle-invasive bladder
      cancer.
AB  - OBJECTIVE: To investigate the role of forkhead box protein M1 (FOXM1) mRNA
      expression and its prognostic value in stage pT1 non-muscle-invasive bladder
      cancer (NMIBC). PATIENTS AND METHODS: Clinical data and formalin-fixed paraffin
      embedded tissues from transurethral resection of the bladder from patients with
      stage pT1 NMIBC, treated with an organ-preserving approach, were analysed
      retrospectively. Total RNA was isolated using commercial RNA extraction kits, and
      mRNA expression of FOXM1, MKI67, KRT20 and KRT5 was measured by single-step
      quantitative RT-PCR using RNA-specific TaqMan Assays. Statistical analysis was
      performed using Spearman's Rho, Wilcoxon or Kruskal-Wallis tests, Kaplan-Meier
      estimates of recurrence-free (RFS), progression-free (PFS) and cancer-specific
      survival (CSS) and Cox regression analysis. RESULTS: Data from 296 patients
      (79.4% men, median age 72 years) were available for the final evaluation.
      Spearman correlation analysis showed that mRNA expression of FOXM1 was
      significantly correlated with MKI67 (rho: 0.6530, P < 0.001) and with the luminal
      subtype, reflected by the positive correlation with KRT20 (rho: 0.2113, P <
      0.001). Furthermore, there was also a strong correlation of FOXM1 expression with
      adverse clinical and pathological variables, such as concomitant carcinoma in
      situ (P = 0.05), multifocal tumours (P = 0.005) and World Health Organization
      1973 grade 3 disease (P < 0.001). Kaplan-Meier analysis showed overexpression of
      FOMX1 to be associated with worse PFS (P = 0.028) and worse CSS (P = 0.015).
      FOXM1 overexpression was also shown to be a predictive risk factor for CSS
      (hazard ratio 1.61 [1.13-2.34], L-R chi-squared: 7.19, P = 0.007). FOXM1
      overexpression identified a subgroup of patients within the luminal subtype with
      worse RFS (P = 0.017), PFS (P < 0.001) and CSS (P = 0.015). Patients with low
      FOXM1 expression had better outcomes, irrespective of instillation therapy,
      whereas patients with high FOXM1 expression benefitted from intravesical
      chemotherapy with mitomycin C. CONCLUSION: High FOXM1 expression was associated
      with adverse clinical and pathological features and worse outcomes, and predicted
      response to intravesical instillation therapy in patients with stage pT1 NMIBC.

PMID- 30120862
TI  - Meeting the needs of young people with psychosis: We must do better.

PMID- 30120863
TI  - The response of the marine nitrogen cycle to ocean acidification.
AB  - Ocean acidification (OA), arising from the influx of anthropogenically generated
      carbon, poses a massive threat to the ocean ecosystems. Our knowledge of the
      effects of elevated anthropogenic CO2 in marine waters and its effect on the
      performance of single species, trophic interactions, and ecosystems is increasing
      rapidly. However, our understanding of the biogeochemical cycling of nutrients
      such as nitrogen is less advanced and lacks a comprehensive overview of how these
      processes may change under OA. We conducted a systematic review and meta-analysis
      of eight major nitrogen transformation processes incorporating 49 publications to
      synthesize current scientific understanding of the effect of OA on nitrogen
      cycling in the future ocean by 2100. The following points were identified by our
      meta-analysis: (a) Diazotrophic nitrogen fixation is likely enhanced by 29% +/-
      4% under OA; (b) species- and strain-specific responses of nitrogen fixers to OA
      were detectable, which may result in alterations in microbial community
      composition in the future ocean; (c) nitrification processes were reduced by a
      factor of 29% +/- 10%; (d) declines in nitrification rates were not reflected by
      nitrifier abundance; and (e) contrasting results in unispecific culture
      experiments versus natural communities were apparent for nitrogen fixation and
      denitrification. The net effect of the nitrogen cycle process responses also
      suggests there may be a shift in the relative nitrogen pools, with excess
      ammonium originating from CO2 -fertilized diazotrophs. This regenerated inorganic
      nitrogen may recycle in the upper water column increasing the relative importance
      of the ammonium-fueled regenerated production. However, several feedback
      mechanisms with other chemical cycles, such as oxygen, and interaction with other
      climate change stressors may counteract these findings. Finally, our review
      highlights the shortcomings and gaps in current understanding of the potential
      changes in nitrogen cycling under future climate and emphasizes the need for
      further ecosystem studies.

PMID- 30120864
TI  - Expression of the Arabidopsis thaliana immune receptor EFR in Medicago truncatula
      reduces infection by a root pathogenic bacterium, but not nitrogen-fixing
      rhizobial symbiosis.
AB  - Interfamily transfer of plant pattern recognition receptors (PRRs) represents a
      promising biotechnological approach to engineer broad-spectrum, and potentially
      durable, disease resistance in crops. It is however unclear whether new
      recognition specificities to given pathogen-associated molecular patterns (PAMPs)
      affect the interaction of the recipient plant with beneficial microbes. To test
      this in a direct reductionist approach, we transferred the Brassicaceae-specific
      PRR ELONGATION FACTOR-THERMO UNSTABLE RECEPTOR (EFR), conferring recognition of
      the bacterial EF-Tu protein, from Arabidopsis thaliana to the legume Medicago
      truncatula. Constitutive EFR expression led to EFR accumulation and activation of
      immune responses upon treatment with the EF-Tu-derived elf18 peptide in leaves
      and roots. The interaction of M. truncatula with the bacterial symbiont
      Sinorhizobium meliloti is characterized by the formation of root nodules that fix
      atmospheric nitrogen. Although nodule numbers were slightly reduced at an early
      stage of the infection in EFR-Medicago when compared to control lines, nodulation
      was similar in all lines at later stages. Furthermore, nodule colonization by
      rhizobia, and nitrogen fixation were not compromised by EFR expression.
      Importantly, the M. truncatula lines expressing EFR were substantially more
      resistant to the root bacterial pathogen Ralstonia solanacearum. Our data suggest
      that the transfer of EFR to M. truncatula does not impede root nodule symbiosis,
      but has a positive impact on disease resistance against a bacterial pathogen. In
      addition, our results indicate that Rhizobium can either avoid PAMP recognition
      during the infection process, or is able to actively suppress immune signaling.

PMID- 30120865
TI  - Effects of clotrimazole troches on tacrolimus dosing in heart transplant
      recipients.
AB  - BACKGROUND: Tacrolimus is a cornerstone of immunosuppression after
      transplantation but is highly susceptible to changes from interacting variables
      and has a narrow therapeutic index. Clotrimazole troches are commonly used as a
      non-systemic antifungal to prevent oral candidiasis. Studies suggest that
      clotrimazole troches, though minimally absorbed systemically, may affect
      tacrolimus concentrations by inhibition of metabolic enzyme activity in the
      intestines. However, the magnitude of the impact of clotrimazole on tacrolimus
      dosing requirements to maintain goal levels is not well described. METHODS: To
      assess this, tacrolimus dose adjustments and trough concentrations were
      retrospectively examined in 95 heart transplant recipients before and after the
      discontinuation of clotrimazole. RESULTS: The median percent tacrolimus dose
      change was an increase of 66.7% (IQR 28.6%, 100%) after clotrimazole
      discontinuation, and the median trough concentration percent change from baseline
      to the first trough after clotrimazole discontinuation (in the absence of a dose
      change) was -42.5% (IQR -52.3%, -30.9%). Five cases of allograft rejection were
      observed. CONCLUSION: In conclusion, clotrimazole troches exert a meaningful
      interaction with tacrolimus that requires close monitoring and dose adjustment.
      The data from this single-center study provide novel information that could guide
      providers on the degree of tacrolimus dose adjustment needed when discontinuing
      clotrimazole prophylaxis after heart transplantation.

PMID- 30120867
TI  - Diagnostic protocols for the management of pregnancy of unknown location.

PMID- 30120866
TI  - Efficacy of brincidofovir as prophylaxis against HSV and VZV in hematopoietic
      cell transplant recipients.
AB  - Allogeneic hematopoietic cell transplant (HCT) recipients are at risk for herpes
      simplex virus (HSV) and varicella-zoster virus (VZV) infections. Routine
      prophylaxis with acyclovir is recommended during periods of immunosuppression.
      Brincidofovir (BCV, CMX001), a lipid conjugate of cidofovir, has shown in vitro
      activity against HSV/VZV, but has not been formally studied for HSV/VZV
      prophylaxis. We report our clinical experience of BCV for HSV/VZV prophylaxis in
      HCT recipients. This was a retrospective review of 30 hematopoietic cell
      transplant (HCT) recipients between 8/2010 and 8/2015 who received BCV doses not
      exceeding 200 mg/week for adults/adolescents and 4 mg/kg/week for pediatric (<12
      years) patients, for >=14 days BCV without concomitant acyclovir under clinical
      trials or single patient use. HSV/VZV cases during BCV treatment were confirmed
      by viral culture or PCR and clinical symptoms. Of 30 patients who met the
      inclusion criteria, 27 (90%) patients were adults and 22 (73%) patients received
      T-cell depleted HCT. The most common indications for BCV were cytomegalovirus in
      12 patients (40%) and adenovirus in 11 patients (37%). One patient was treated
      for acyclovir-resistant HSV and one for disseminated VZV. There were two
      breakthrough cases of HSV infection during 2170 patient-days. There were no cases
      of breakthrough VZV infection. The overall rate of breakthrough HSV infection was
      1.0 per 1000 patient-days, without any breakthrough VZV infections. Our study
      provides the only available-albeit limited-evidence on the potential efficacy of
      BCV for HSV/VZV prophylaxis in HCT patients. Additional studies are needed to
      further assess the efficacy and safety of BCV in the setting.

PMID- 30120869
TI  - Rapid evolution in native plants cultivated for ecological restoration: not a
      general pattern.
AB  - The growing number of restoration projects worldwide increases the demand for
      seed material of native species. To meet this demand, seeds are often produced
      through large-scale cultivation on specialized farms, using wild-collected seeds
      as the original sources. However, during cultivation plants experience novel
      environmental conditions compared to those in natural populations, and there is a
      danger that the plants in cultivation are subject to unintended selection and
      lose their adaptation to natural habitats. Although the propagation methods are
      usually designed to maintain as much natural genetic diversity as possible, the
      effectiveness of these measures have never been tested. We obtained seeds of five
      common grassland species from one of the largest native seed producers in
      Germany. For each species, the seeds were from multiple generations of seed
      production. We used AFLP markers and a common garden experiment to test for
      genetic and phenotypic changes during cultivation of these plants. The molecular
      markers detected significant evolutionary changes in three out of the five
      species, and we found significant phenotypic changes in two species. The only
      species that showed substantial genetic and phenotypic changes was the short
      lived and predominantly selfing Medicago lupulina, where in the other, mostly
      perennial and outcrossing species, the observed changes were mostly minor.
      Agricultural propagation of native seed materials for restoration can cause
      evolutionary changes, at least in some species. We recommend caution particularly
      in selfing and short-lived species, where evolution may happen faster and effects
      may thus be more severe. This article is protected by copyright. All rights
      reserved.

PMID- 30120868
TI  - Alternate splicing of transcripts upon Mycobacterium tuberculosis infection
      impacts the expression of functional protein domains.
AB  - Previously, we reported that infection of human macrophages with Mycobacterium
      tuberculosis (Mtb) results in massive alterations in the pattern of RNA splicing
      in the host. The finding gained significance since alternate spliced variants of
      a same gene may have substantially different structure, function, stability,
      interaction partners, localization, and so forth, owing to inclusion or exclusion
      of specific exons. To establish a proof-of-concept; on how infection-induced RNA
      splicing could impact protein functions, here we used RNA-seq data from THP-1
      macrophages that were infected with clinical isolate of Mtb. In addition to re
      establishing the fact that Mtb infection may cause strain specific alterations in
      RNA splicing, we also developed a new analysis pipeline resulting in
      characterization of domain maps of the transcriptome post-infection. For the sake
      of simplicity, we restricted our analysis to all the kinases in the human genome
      and considered only pfam classified protein domains and checked their frequency
      of inclusion or exclusion due to alternate splicing across the conditions and
      time points. We report massive alterations in the domain architecture of most
      regulated proteins across the entire kinases highlighting the physiological
      importance of such an understanding. This study paves way for more detailed
      analysis of different functional classes of proteins and perturbations to their
      domain architecture as a consequence of mycobacterial infections. Such analysis
      would yield unprecedented depth to our understanding of host-pathogen interaction
      and allow in a more systematic manner targeting of host pathways for controlling
      the infections. (c) 2018 The Authors. IUBMB Life published by Wiley Periodicals,
      Inc. on behalf of International Union of Biochemistry and Molecular Biology,
      70(9):845-854, 2018.

PMID- 30120870
TI  - Short and long-term outcomes in children born after assisted reproductive
      technologies (ART).
AB  - It has been forty years since the first IVF child, Louise Brown, born in 1978 and
      now more than 7 million children are conceived after assisted reproductive
      technologies (ART). There has been a tremendous increase in the number of ART
      cycles and several more advanced treatments have been developed, such as
      intracytoplasmic sperm injection (ICSI). ICSI revolutionized the treatment of
      severe male factor infertility after the first ICSI baby born in 1992. This
      article is protected by copyright. All rights reserved.

PMID- 30120871
TI  - Tuberculosis: Today's researches-tomorrow's therapies.

PMID- 30120872
TI  - Towards a characterisation of the wild legume bitter vetch (Lathyrus linifolius
      L. (Reichard) Bassler): heteromorphic seed germination, root nodule structure and
      N-fixing rhizobial symbionts.
AB  - Lathyrus linifolius L. (Reichard) Bassler (Fabiaceae, bitter vetch) is a nitrogen
      (N) fixing species. A coloniser of low nutrient (N) soils, it supports
      biodiversity such as key moth and butterfly species, and its roots are known for
      their organoleptic and claimed therapeutic properties. Thus, the species has high
      potential for restoration, conservation, novel cropping and as a model species.
      The last because of its genetic synteny with important pulse crops. However,
      regeneration and functional attributes of L. linifolius remain to be
      characterised. Seeds of L. linifolius were characterised using physical,
      colorimetric and chemical data. Ultrastructural and functional characterisation
      of the N-fixing root nodules included immunolabelling with nifH protein
      antibodies (recognising the N-fixing enzyme, nitrogenase). Endosymbiotic bacteria
      were isolated from root nodules and characterised phylogenetically using 16S
      rRNA, nodA and nodD gene sequences. L. linifolius yielded heteromorphic seed of
      distinct colour classes: green and brown. Seed morphotypes had similar C:N ratios
      and were equally germinable (ca. 90%) after scarification at differing optimal
      temperatures (16 and 20  degrees C). Brown seeds were larger and comprised a
      larger proportion of the seed batch (69%). L. linifolius root nodules appeared
      indeterminate in structure, effective (capable of fixing atmospheric N) and
      having strains very similar to Rhizobium leguminosarum biovar viciae. The
      findings and rhizobial isolates have potential application for ecological
      restoration and horticulture using native seeds. Also, the data and rhizobial
      resources have potential applications in comparative and functional studies with
      related and socio-economically important crops such as Pisum, Lens and Vicia.

PMID- 30120873
TI  - Variation in seclusion rates across New Zealand's specialist mental health
      services: Are sociodemographic and clinical factors influencing this?
AB  - Rates of seclusion vary across New Zealand's publicly funded district health
      board (DHB) adult mental health inpatient services as indicated by national data.
      Anecdotally, this variation has been attributed to a range of factors directly
      relating to the people admitted to acute inpatient services. This study examined
      the extent to which variation in seclusion rates could be explained by the
      sociodemographic and clinical differences between populations admitted into adult
      mental health inpatient services. Retrospective data were obtained from the
      Programme for the Integration of Mental Health Data (PRIMHD). A logistic
      regression model was fitted to these data, with seclusion (yes/no) as the
      dependent variable and DHB groups as the independent variable. The DHBs were
      classified into four groups based on their seclusion rates. The model adjusted
      for ethnicity, age, number of bed nights, total Health of the Nation Outcome
      Scales (HoNOS) scores, and compulsory treatment status. Odds ratios remained
      virtually unchanged after adjustment for sociodemographic and clinical factors.
      People admitted to DHB Group 4 (highest secluding DHBs) were 11 times more likely
      to be secluded than people in Group 1 (lowest secluding DHBs), adjusted OR =
      11.1, 95% CI [7.5,16.4], P < 0.001. Results indicate DHB variation in seclusion
      rates cannot be attributed to the sociodemographic and clinical factors of people
      admitted into DHB adult mental health inpatient services. Instead, this variation
      may be explained by differences in service delivery models and practice
      approaches. A model of system improvements aimed at reducing seclusion is
      discussed.

PMID- 30120874
TI  - Help-seeking experiences of older adults with a diagnosis of moderate depression.
AB  - Depression is the most prevalent mental illness among older adults. However, help
      seeking by older adults is frequently delayed, resulting in longer duration of
      untreated symptoms, poorer health outcomes, and consequent higher healthcare use.
      Early help-seeking and access to appropriate support benefits individuals, while
      providing better outcomes from health systems constrained by limited resources.
      The aim of this study, which is abstracted from a larger study, was to identify
      the factors that inhibited and enabled formal help-seeking in older adults with a
      diagnosis of moderate depression. Corbin and Strauss' approach to grounded theory
      informed data collection and analysis. Two themes and related subthemes
      concerning help-seeking barriers and facilitators were abstracted from the data.
      Help-seeking barriers were attributable to stigma, self-motivation, accessing
      formal support, ageism, and difficulty obtaining an initial diagnosis. Help
      seeking facilitators were accepting personal responsibility, mental health
      literacy, therapeutic alliances, and informal support. Findings have implications
      for the role of mental health nurses, who are well-placed to provide support to
      community-based older adults with depression. More broadly, mental health nurses
      and other clinicians should seek to reduce help-seeking barriers and implement
      ways to facilitate help-seeking in this cohort.

PMID- 30120875
TI  - Regulation of antigen 85C activity by reversible S-glutathionylation.
AB  - Mycobacterium tuberculosis is the causative agent of many strains of
      tuberculosis, as it is composed of an impenetrable, complex cell wall. The
      proteins active in the synthesis of the cell wall are mycolyl transferase
      antigens 85A, 85B, and 85C, encoded by genes fbpA, fbpB, and fbpC. Antigen 85C
      contains one cysteine residue. S-Glutathionylation is the formation of a mixed
      disulfide between a protein cysteine residue and glutathione (GSH), an abundant
      antioxidant molecule. It is a post-translational modification of cysteine
      residues which can occur under oxidative stress or physiological conditions. It
      is a known mechanism to regulate enzyme activity, signaling pathways, and the
      progression of diseases. By S-glutathionylation, the lone cysteine residue in
      antigen 85C is modified by biotinylated GSH ethyl ester to form a mixed
      disulfide. This modification results in a decrease in enzyme activity by 90%,
      representing a decrease in ability of the protein to synthesize the bacterial
      cell wall. Both the modification and the enzymatic activity of the protein are
      concentration dependent and can be reversed upon addition of a thiol reducing
      agent. The results provide a potential strategy for inhibiting the synthesis of
      the cell wall of M. tuberculosis by promoting oxidation of the lone cysteine
      residue. To our knowledge, this is a novel finding to demonstrate the
      modification of antigen 85C and the regulation of its activity by a physiological
      molecule. (c) 2018 IUBMB Life, 70(11):1111-1114, 2018.

PMID- 30120876
TI  - LncRNA SNHG20 is associated with clinical progression and enhances cell migration
      and invasion in osteosarcoma.
AB  - SNHG20 is a novel lncRNA which has been showed to be overexpressed and functions
      as oncogenic lncRNA in several types of human cancer. The role of SNHG20 in
      osteosarcoma is still unknown. The purpose of our study was to identify the
      clinical value and biological function of SNHG20 in osteosarcoma. Our results
      indicated SNHG20 was overexpressed in osteosarcoma tissues and cell lines
      compared with paired non-tumor tissues and normal human osteoblast cell line,
      respectively. Moreover, we observed high-expression of SNHG20 was obviously
      associated with Enneking stage, distant metastasis, and histological grade.
      SNHG20 expression was negatively associated with overall survival, and high
      expression of SNHG20 was an independent unfavorable prognostic factor in
      osteosarcoma patients. Furthermore, SNHG20 promoted osteosarcoma cell migration
      and invasion through modulating epithelial-mesenchymal transition -associated
      genes. In conclusion, SNHG20 is an independent unfavorable prognostic factor in
      osteosarcoma patients, and functions as an oncogenic lncRNA to modulate tumor
      cell migration and invasion. (c) 2018 IUBMB Life, 70(11):1115-1121, 2018.

PMID- 30120877
TI  - Hydrogen Flush After Cold Storage as a New End-Ischemic Ex Vivo Treatment for
      Liver Grafts Against Ischemia/Reperfusion Injury.
AB  - Cold storage (CS) remains the gold standard for organ preservation worldwide,
      although it is inevitably associated with ischemia/reperfusion injury (IRI).
      Molecular hydrogen (H2 ) is well known to have antioxidative properties. However,
      its unfavorable features, ie, inflammability, low solubility, and high
      tissue/substance permeability, have hampered its clinical application. To
      overcome such obstacles, we developed a novel reconditioning method for donor
      organs named hydrogen flush after cold storage (HyFACS), which is just an end
      ischemic H2 flush directly to donor organs ex vivo, and, herein, we report its
      therapeutic impact against hepatic IRI. Whole liver grafts were retrieved from
      Wistar rats. After 24-hour CS in UW solution, livers were cold-flushed with H2
      solution (1.0 ppm) via the portal vein (PV), the hepatic artery (HA), or both (PV
      + HA). Functional integrity and morphological damages were then evaluated by 2
      hour oxygenated reperfusion at 37 degrees C. HyFACS significantly lowered portal
      venous pressure, transaminase, and high mobility group box protein 1 release
      compared with vehicle-treated controls (P < 0.01). Hyaluronic acid clearance was
      significantly higher in the HyFACS-PV and -PV + HA groups when compared with the
      others (P < 0.01), demonstrating the efficacy of the PV route to maintain the
      sinusoidal endothelia. In contrast, bile production and lactate dehydrogenase
      leakage therein were both significantly improved in HyFACS-HA and -PV + HA (P <
      0.01), representing the superiority of the arterial route to attenuate biliary
      damage. Electron microscopy consistently revealed that sinusoidal ultrastructures
      were well maintained by portal HyFACS, while microvilli in bile canaliculi were
      well preserved by arterial flush. As an underlying mechanism, HyFACS
      significantly lowered oxidative damages, thus improving the
      glutathione/glutathione disulfide ratio in liver tissue. In conclusion, HyFACS
      significantly protected liver grafts from IRI by ameliorating oxidative damage
      upon reperfusion in the characteristic manner with its route of administration.
      Given its safety, simplicity, and cost-effectiveness, end-ischemic HyFACS may be
      a novel pretransplant conditioning for cold-stored donor organs.

PMID- 30120878
TI  - The activity and action mechanism of novel short selective LL-37-derived
      anticancer peptides against clinical isolates of Escherichia coli.
AB  - Human cathelicidin LL-37 has recently attracted interest as a potential
      therapeutic agent, mostly because of its ability to kill a wide variety of
      pathogens and cancer cells. In this study, we aimed to investigate the
      antibacterial activity and cytotoxicity of previously designed LL-37 anticancer
      derivatives (i.e., P7, P22, and P38). Calcein release assay and field emission
      scanning electron microscopy (FE-SEM) were performed to elucidate the possible
      mechanism of action of P38, the peptide with the highest bactericidal activity.
      In silico analysis demonstrated the amphipathic alpha-helical structure for three
      peptides. Antibacterial activity of P38 against multidrug-resistant (MDR)
      clinical isolates of Escherichia coli was higher than that of P7 and P22. P38
      caused no hemolysis or cytotoxicity. Treating calcein-loaded E. coli with 4* MIC
      of P38 resulted in more than 96% leakage of calcein. Noticeably, FE-SEM revealed
      that P38 killed E. coli by disrupting the bacterial membrane. Molecular docking
      studies showed that P38 had a much higher affinity for the outer membrane of Gram
      negative bacteria compared with both P22 and P7. Owing to the bactericidal
      activity of P38 against MDR E. coli isolates and its negligible cytotoxicity, P38
      has the potential for further studies in a mouse model of infectious disease.

PMID- 30120879
TI  - Design, synthesis, and biological evaluation of 2-(4
      (methylsulfonyl)phenyl)pyridine derivatives as GPR119 agonists.
AB  - This study describes the design, synthesis, and biological evaluation of a series
      of novel small molecule GPR119 agonists with improved potency and moderate
      physiochemical characteristics. Among them, the most promising compounds 19 and
      20 were obtained with EC50 values of 75 and 25 nM, respectively, in vitro cAMP
      assays and effectively decreased blood glucose excursion in oral glucose
      tolerance test (OGTT) of normal mice. Furthermore, in OGTT with type 2 diabetic
      mice induced by streptozotocin and high-fat diet, compound 19 also showed
      significant reduction in blood glucose level compared to vehicle control group,
      which demonstrated an attractive in vitro and in vivo profile for further
      development.

PMID- 30120880
TI  - Lipid peroxidation, DNA damage, and apoptosis in dengue fever.
AB  - Interplay between the apoptosis, DNA damage, and oxidative stress as a host
      response to dengue viral infections remains unclear. Peripheral blood mononuclear
      cells (PBMCs) were isolated from 60 dengue infected patients, 20 patients with
      febrile illness other than dengue (OFI) and 10 non-febrile illness (NFI)
      patients. DNA damage in the PBMCs was assessed using single cell gel
      electrophoresis and stages of apoptosis underwent by the PBMCs were studied by
      Annexin-PI staining using flow cytometry. Plasma levels of malondialdehyde levels
      were estimated using thiobarbituric acid assay. Dengue infected individuals had
      showed increased DNA damage than NFI and OFI controls at the time of admission.
      Annexin-PI staining revealed increased frequency of apoptotic cells in dengue
      infected PBMCs than controls during the admission time. Similar pattern was
      observed in samples collected around defervescence. Within the dengue cases,
      percentage of live cells was higher in non-severe dengue than severe dengue at
      both the time points. Follow-up samples in dengue showed less number of live
      cells and higher percentage of apoptotic cells with respect to their baseline and
      this was reversed in case of OFI. Plasma malondialdehyde levels were found to be
      relatively higher in dengue cases than controls at admission and around
      defervescence. Significant positive correlation between DNA damage, apoptosis,
      and plasma malondialdehyde levels might pave a way for understanding the complex
      interactions between virus and hosts response thereby aids in identifying
      plausible immunopathological links contributing to disease pathogenesis. (c) 2018
      IUBMB Life, 70(11):1133-1143, 2018.

PMID- 30120882
TI  - Crystal structure of phospholipase A2 in complex with 1-naphthaleneacetic acid.
AB  - Phospholipase A2 (PLA2 ) is one of the rate limiting enzymes involved in the
      production of arachidonic acid, a potent inflammatory mediator. PLA2 is widely
      distributed all over the animal kingdom. It is also seen in inflammatory
      exudation and venoms of different organisms. The studies demonstrated that PLA2
      inhibitors have broad spectrum activities that they can either be used against
      inflammation or envenomation. In this study, the inhibitory activity of 1
      napthaleneacetic acid (NAA) against porcine pancreatic PLA2 has been explained
      through isothermal titration calorimetry and enzyme kinetics studies. The atomic
      level of interactions of NAA with PLA2 was also studied using X-ray
      crystallography. Apart from these findings, the theoretical binding affinities
      and mode of interactions of two naphthalene-based NSAIDs such as naproxen (NAP)
      and nabumetone (NAB) were studied through molecular modeling. The studies proved
      that the selected ligands are binding at the doorway of the active site cleft and
      hindering the substrate entry to the active site. The study brings out a
      potential scaffold for the designing of broad spectrum PLA2 inhibitors which can
      be used for inflammation or envenomation. (c) 2018 IUBMB Life, 70(10):995-1001,
      2018.

PMID- 30120883
TI  - Association of FOLH1, DHFR, and MTHFR gene polymorphisms with susceptibility of
      Neural Tube Defects: A case control study from Eastern India.
AB  - BACKGROUND: Worldwide, Neural tube defects (NTDs) are considered as major
      clinical problems imposing a huge socio-economic burden for both affected
      individuals and their families. In India, the prevalence of Neural tube defects
      is significantly high. This study aims to evaluate the association between
      genetic defects in folate metabolism pathway genes, mainly: Folate hydrolase 1
      (FOLH1), Dihydrofolate reductase (DHFR) and Methylenetetrahydrofolate reductase
      (MTHFR) and neural tube defects from eastern India. METHODS: We enrolled 62
      consecutive mothers with NTDs foetuses as cases and their corresponding age
      matched 73 mothers with healthy babies as controls (genetic power has been
      calculated). Four single nucleotide polymorphisms (FOLH1: rs202676, DHFR:
      rs70991108, MTHFR: rs1801133 and rs1801131) have been amplified by polymerase
      chain reaction (PCR) and sequenced. Statistical analysis has been undertaken to
      find out association with NTDs. RESULTS: Genotype and allele frequency analysis
      of these SNPs revealed that, rs1801133 (p.Ala222Val) was significantly associated
      with NTDs risk (p value = 0.028; odds ratio-2.31; 95% CI 1.08-4.93), whereas
      rs202676 (p.Tyr60His) showed protective role (p value = 0.0066; odds ratio-0.11;
      95% CI 0.01-0.86). Serum homocysteine (Hcy) concentration was respectively higher
      in subjects carrying 222Ala/Val and 222Val/Val alleles (p value = 0.009; p value
      <= 0.0001). CONCLUSION: In conclusion, it can be stated that, rs1801133 was
      associated with neural tube defects risk in patients from the eastern part of
      India and it might be counted as a molecular marker for evaluating the
      susceptibility of NTDs.

PMID- 30120884
TI  - Seed traits and germination behaviour of four Sardinian populations of
      Helichrysum microphyllum subsp. tyrrhenicum (Asteraceae) along an altitudinal
      gradient.
AB  - Helichrysum microphyllum subsp. tyrrhenicum (Asteraceae) is an endemic taxon of
      Sardinia and Corsica, where it grows at different altitudes. The objective of
      this study was to investigate the seed traits and germination behaviour of four
      Sardinian populations of this taxon located at different altitudes. Seed traits
      were evaluated, and germination tests were carried out by incubating seeds at a
      range of constant (5-30  degrees C) and alternating (25/10  degrees C)
      temperatures. The dry after-ripening (DAR) pre-treatment was also applied by
      storing seed in dry conditions for 3 months at 25  degrees C. Seed traits and
      germination behaviour data were statistically analysed to identify if there was a
      correlation with altitude. Differences in seed size, area and mass among
      populations were recorded, however, no relationship was found with altitude. High
      germination percentages were obtained in all populations, both in untreated and
      DAR seeds, and were positively affected by alternating temperatures. The final
      germination percentage and time required to reach 50% final germination (T50 )
      showed no relationship with altitude. The differences in seed traits and
      germination detected among the studied populations of H. microphyllum subsp.
      tyrrhenicum were not correlated with altitude. This study provides new and
      important knowledge for this taxon. H. microphyllum subsp. tyrrhenicum is
      characterised by high germination percentages and low T50 values and does not
      seem to require any dormancy-breaking treatment. This species represents a high
      potential native plant species that should be considered within environmental
      management plans.

PMID- 30120881
TI  - Na+ , K+ -ATPase activity in children with autism spectrum disorder: Searching
      for the reason(s) of its decrease in blood cells.
AB  - Na+ , K+ -ATPase (NKA) activity, which establishes the sodium and potassium
      gradient across the cell membrane and is instrumental in the propagation of the
      nerve impulses, is altered in a number of neurological and neuropsychiatric
      disorders, including autism spectrum disorders (ASD). In the present work, we
      examined a wide range of biochemical and cellular parameters in the attempt to
      understand the reason(s) for the severe decrease in NKA activity in erythrocytes
      of ASD children that we reported previously. NKA activity in leukocytes was found
      to be decreased independently from alteration in plasma membrane fluidity. The
      different subunits were evaluated for gene expression in leukocytes and for
      protein expression in erythrocytes: small differences in gene expression between
      ASD and typically developing children were not apparently paralleled by
      differences in protein expression. Moreover, no gross difference in erythrocyte
      plasma membrane oxidative modifications was detectable, although oxidative stress
      in blood samples from ASD children was confirmed by increased expression of NRF2
      mRNA. Interestingly, gene expression of some NKA subunits correlated with
      clinical features. Excess inhibitory metals or ouabain-like activities, which
      might account for NKA activity decrease, were ruled out. Plasma membrane
      cholesterol, but not phosphatidylcholine and phosphatidlserine, was slighty
      decreased in erythrocytes from ASD children. Although no compelling results were
      obtained, our data suggest that alteration in the erytrocyte lipid moiety or
      subtle oxidative modifications in NKA structure are likely candidates for the
      observed decrease in NKA activity. These findings are discussed in the light of
      the relevance of NKA in ASD. Autism Res 2018, 11: 1388-1403. (c) 2018
      International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY:
      The activity of the cell membrane enzyme NKA, which is instrumental in the
      propagation of the nerve impulses, is severely decreased in erythrocytes from ASD
      children and in other brain disorders, yet no explanation has been provided for
      this observation. We strived to find a biological/biochemical cause of such
      alteration, but most queries went unsolved because of the complexity of NKA
      regulation. As NKA activity is altered in many brain disorders, we stress the
      relevance of studies aimed at understanding its regulation in ASD.

PMID- 30120885
TI  - Cryptococcal infection in lung transplant recipients: A 5-year retrospective
      review at an Australian transplant center.
AB  - Cryptococcosis is a common invasive fungal infection (IFI) in solid organ
      transplant (SOT) recipients. Little is known about cryptococcosis in lung
      transplant (LTx) recipients despite having one of the highest risks of infection.
      The aim of this study was to describe demographic and clinical features of
      cryptococcal infection in LTx recipients. We performed a retrospective,
      observational study of cryptococcal infection in LTx recipients at The Alfred
      Hospital in Melbourne, Australia, from 2012 to 2017. A total of 11 cases were
      identified. Seven patients (64%) were male and the median age was 54.7 years
      (range 34-69 years). Diagnosis occurred at a median of 233 days (range 1-3650
      days) post-transplant. Nine patients (82%) had isolated pulmonary infection of
      whom 7 (78%) were asymptomatic. All were treated with oral antifungal therapy and
      1 required surgical resection of infected lung. Two patients (18%) had
      disseminated infection; 1 with pulmonary and central nervous system (CNS)
      infection and 1 with isolated CNS infection. Both patients presented with
      headache and brain imaging demonstrated cerebral edema, myelinosis, and
      leptomeningeal enhancement. One of these patients died. This study highlights the
      fact that cryptococcal infection should remain a consideration in asymptomatic
      LTx recipients, especially in the presence of non-specific nodules on chest
      imaging, and that the presence of headache in these patients requires urgent
      investigation for CNS infection.

PMID- 30120886
TI  - Physiology on television.

PMID- 30120887
TI  - Impact of hidradenitis suppurativa on work loss, indirect costs and income.
AB  - BACKGROUND: Hidradenitis suppurativa (HS), a chronic cutaneous disease, can
      negatively affect work life. OBJECTIVES: This retrospective cohort study
      evaluates the indirect burden among employed patients with HS in the U.S.A.
      METHODS: Newly diagnosed and general patients with HS, who were employees (age 18
      64 years) from a large claims database (Q1 1999 to Q1 2015), were matched 1 : 5
      to controls. Income growth and risk of leaving the workforce were assessed among
      the newly diagnosed HS and control cohorts in the 5-year study period. Income,
      work loss days and indirect costs (absenteeism and disability) were assessed
      among the general HS and control cohorts in the 1-year study period. RESULTS:
      Newly diagnosed (n = 1003, mean age 39.5 years, 66.3% female) and general
      patients with HS (n = 1204, mean age 39.9 years, 69.1% female) were matched to
      5015 and 6020 controls, respectively. Newly diagnosed patients with HS had
      significantly slower income growth ($324 per year) and higher risk of leaving the
      workforce (adjusted hazard ratio 1.65, 95% confidence interval 1.45-1.88)
      compared with controls (all P < 0.05). General patients with HS had more total
      days of work loss (18.4 vs. 7.7), higher annual total indirect costs ($2925 vs.
      $1483) and lower annual income ($54 925 vs. $62 357) than controls (all P <
      0.001). CONCLUSIONS: Patients with newly diagnosed HS and general patients with
      HS experienced a greater indirect burden than matched controls.

PMID- 30120888
TI  - A touch of awe: crafting meaning from the wonder of the cosmos.
AB  - From the birth of galaxies to the self-organizing dynamics of our planet to the
      ongoing expansion of the universe, the more we discover about the evolution of
      the cosmos, the more acutely we realize the enormity of what remains to be known.
      Just this year astrophysicists at the University of Nottingham confirmed that
      there are at least two trillion galaxies in the cosmos, 10 times more than had
      been previously thought. What guidance or wisdom can the study of cosmology and
      astrophysics offer us in our search for meaning and purpose? In conversation with
      Steve Paulson, executive producer and host of To the Best of Our Knowledge,
      theoretical physicists Paul Davies and Ard Louis, and astrophysicist Lucianne
      Walkowicz share their perceptions based on years of gazing upward and beyond our
      own intimate planet.

PMID- 30120889
TI  - Biosurfactants from probiotic bacteria: A review.
AB  - Among microorganisms, bacteria are the main group of biosurfactant-producing
      organisms. Different types of bacteria including Pseudomonas sp., Acinetobacter
      sp., Bacillus sp., and Arthrobacter sp. are among the most commonly studied
      bacteria in the realm of scientific research. However, due to the pathogenic
      nature of the producing organisms, the application of these compounds is
      restricted, therefore, not suitable for use in food-related industries. Given
      that probiotic bacteria impact human health, applying probiotics as nonpathogenic
      and safe organisms have gained much attention for the production of
      biosurfactants in recent years. Most biosurfactants obtained from probiotic
      bacteria are related to a number of lactic acid bacteria (LAB). These types of
      biosurfactants are classified based on their structures as protein-carbohydrate
      complexes, lipids, or fatty acids. The present paper seeks to provide
      comprehensive and useful information about the production of various kinds of
      biosurfactants by different probiotic bacteria. In addition, we have extensively
      reviewed their potential for possible future applications.

PMID- 30120890
TI  - Noninvasive, tube-based, continuous vagal nerve monitoring using the laryngeal
      adductor reflex: Feasibility study of 134 nerves at risk.
AB  - BACKGROUND: Continuous vagal intraoperative neuromonitoring (IONM) currently
      requires placement of a vagal nerve electrode. Herein, we present data from 100
      patients (134 nerves-at-risk) monitored continuously during neck endocrine
      surgeries using a noninvasive, new methodology that solely utilizes endotracheal
      tube electrodes to simultaneously stimulate laryngeal mucosa and record a
      laryngeal adductor reflex continuous IONM (LAR-C-IONM) response. METHODS: The
      laryngeal adductor reflex (LAR) was elicited by electrical laryngeal mucosal
      stimulation on the side contralateral to the operative field using endotracheal
      tube electrodes. All patients completed preoperative and postoperative laryngeal
      and voice examinations. RESULTS: One hundred patients (134 nerves-at-risk) were
      included. Significantly more nerves-at-risk with an LAR opening to closing
      amplitude decrement >60% or with absolute closing amplitude <100 MUV had
      postoperative vocal fold paralysis (P < .001). The LAR-C-IONM was highly
      sensitive to recurrent laryngeal nerve (RLN) stretch or compression. CONCLUSION:
      The LAR-C-IONM is a promising new way to perform continuous vagal monitoring that
      requires no equipment other than an electromyography (EMG) endotracheal tube and
      is undergoing further, large-scale evaluation.

PMID- 30120891
TI  - Impact of recent and future climate change on vector-borne diseases.
AB  - Climate change is one of the greatest threats to human health in the 21st
      century. Climate directly impacts health through climatic extremes, air quality,
      sea-level rise, and multifaceted influences on food production systems and water
      resources. Climate also affects infectious diseases, which have played a
      significant role in human history, impacting the rise and fall of civilizations
      and facilitating the conquest of new territories. Our review highlights
      significant regional changes in vector and pathogen distribution reported in
      temperate, peri-Arctic, Arctic, and tropical highland regions during recent
      decades, changes that have been anticipated by scientists worldwide. Further
      future changes are likely if we fail to mitigate and adapt to climate change.
      Many key factors affect the spread and severity of human diseases, including
      mobility of people, animals, and goods; control measures in place; availability
      of effective drugs; quality of public health services; human behavior; and
      political stability and conflicts. With drug and insecticide resistance on the
      rise, significant funding and research efforts must to be maintained to continue
      the battle against existing and emerging diseases, particularly those that are
      vector borne.

PMID- 30120892
TI  - Long-term 52-week trends in apremilast safety outcomes for treatment of psoriasis
      in clinical practice: a multicentre, retrospective case series.

PMID- 30120893
TI  - Early arrival at breeding grounds: Causes, costs and a trade-off with
      overwintering latitude.
AB  - Early arrival at breeding grounds is of prime importance for migrating birds as
      it is known to enhance breeding success. Adults, males and higher quality
      individuals typically arrive earlier, and across years, early arrival has been
      linked to warmer spring temperatures. However, the mechanisms and potential costs
      of early arrival are not well understood. To deepen the understanding of arrival
      date differences between individuals and years, we studied them in light of the
      preceding spring migration behaviour and atmospheric conditions en route. GPS and
      body acceleration (ACC) data were obtained for 35 adult white storks (Ciconia
      ciconia) over five years (2012-2016). ACC records were translated to energy
      expenditure estimates (overall dynamic body acceleration; ODBA) and to
      behavioural modes, and GPS fixes were coupled with environmental parameters. At
      the interindividual level (within years), early arrival was attributed primarily
      to departing earlier for migration and from more northern wintering sites (closer
      to breeding grounds), rather than to migration speed. In fact, early-departing
      birds flew slower, experienced weaker thermal uplifts and expended more energy
      during flight, but still arrived earlier, emphasizing the cost and the
      significance of early departure. Individuals that wintered further south arrived
      later at the breeding grounds but did not produce fewer fledglings, presumably
      due to positive carry-over effects of advantageous wintering conditions
      (increased precipitation, vegetation productivity and daylight time). Therefore,
      early arrival increased breeding success only after controlling for wintering
      latitude. Males arrived slightly ahead of females. Between years, late arrival
      was linked to colder temperatures en route through two different mechanisms:
      stronger headwinds causing slower migration and lower thermal uplifts resulting
      in longer stopovers. This study showed that distinct migratory properties
      underlie arrival time variation within and between years. It highlighted (a) an
      overlooked cost of early arrival induced by unfavourable atmospheric conditions
      during migration, (b) an important fitness trade-off in storks between arrival
      date and wintering habitat quality and (c) mechanistic explanations for the
      negative temperature-arrival date correlation in soaring birds. Such
      understanding of arrival time can facilitate forecasting migrating species
      responses to climate changes.

PMID- 30120894
TI  - Liver complications following treatment of hematologic malignancy with anti-cd22
      calicheamicin (Inotuzumab Ozogamicin).
AB  - BACKGROUND AND RATIONALE: Treatment of hematologic malignancy with antibody-drug
      conjugates (ADC) may cause liver injury. ADCs deliver a toxic moiety into antigen
      expressing tumor cells but may also injure hepatic sinusoids (Sinusoidal
      Obstruction Syndrome, SOS). We studied patients who received an anti-CD22
      calicheamicin conjugate (inotuzumab ozogamicin) to gain insight into mechanisms
      of sinusoidal injury, as there are no CD22+ cells in the normal liver but non
      specific uptake of ADCs by liver sinusoidal endothelial cells. METHODS: 638
      patients (307 with acute lymphocytic leukemia (ALL), 311 with non-Hodgkins
      lymphoma) were randomized to either inotuzumab ozogamicin or standard
      chemotherapy (controls). While blinded to treatment assignment, we reviewed all
      cases with hepatobiliary complications to adjudicate the causes. RESULTS: The
      frequency of SOS among patients who received inotuzumab ozogamicin was 5/328
      (1.5%), compared to no cases among 310 control patients. Drug-induced liver
      injury (DILI) developed in 26 (7.9%) inotuzumab ozogamicin recipients and 3 (1%)
      controls. Intrahepatic cholestasis was seen in 4.9% of inotuzumab ozogamicin
      recipients and in 5.5% of controls. Subsequent to the randomization study, 113
      patients with ALL underwent allogeneic hematopoietic cell transplantation; the
      frequency of SOS in those previously exposed to InO was 21/79 (27%) vs. 3/34 (9%)
      in controls. An exploratory multivariate model identified a past history of liver
      disease and thrombocytopenia before conditioning therapy as dominant risk factors
      for SOS after transplant. CONCLUSIONS: The frequencies of SOS and DILI after
      inotuzumab ozogamicin treatment were 1.5% and 7.9%, respectively, compared to
      none and 1% among controls who received standard chemotherapy. These data suggest
      that ADCs that do not target antigens present in the normal liver have a
      relatively low frequency of SOS but a relatively high frequency of DILI. This
      article is protected by copyright. All rights reserved.

PMID- 30120896
TI  - Neuropsychiatric symptoms in hepatitis C patients resemble those of patients with
      autoimmune liver disease but are different from those in hepatitis B patients.
AB  - Chronic fatigue, mood alterations and cognitive impairment are frequent accessory
      symptoms of HCV-infection. Fatigue and mood alterations have also been observed
      in autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC), but not in
      hepatitis B virus (HBV)-infection, thus indicating an autoimmune response as
      possible cause of HCV-infection associated encephalopathy. Data, however, are
      sparse. This study aims to prove that HCV patients feature similar to those with
      autoimmune liver disease but contrary to HBV patients regarding neuropsychiatric
      symptoms. 132 non-cirrhotic patients (HCV: 46, HBV: 22, AIH: 27, PBC: 29,
      AIH/PBC: 8) completed questionnaires addressing the domains mentioned above.
      Eighty-eight underwent a comprehensive neuropsychological assessment. Patient
      groups were compared among each other and to 33 healthy controls. Fatigue,
      anxiety and depression scores were significantly increased, and the SF-36 mental
      score significantly decreased in all patient groups compared to controls. Fatigue
      was significantly more pronounced in HCV than in HBV patients. HCV patients
      scored significantly worse than HBV patients but not AIH and PBC patients in the
      SF-36. HCV, AIH and PBC but not HBV patients did significantly worse than
      controls in word learning. Recognition of words was impaired in HCV, AIH and PBC
      patients and recognition of figures in HCV patients, exclusively (p<=0.002). HCV
      patients did also worse than controls and HBV patients concerning alertness and
      working memory (p<= 0.001). The neuropsychiatric profiles of HCV patients are
      similar to those of AIH and PBC patients but differ from those of HBV patients,
      suggesting an autoimmune response as a possible cause for these differences. This
      article is protected by copyright. All rights reserved.

PMID- 30120897
TI  - Hepatic zonation now on hormones!
AB  - The liver plays important roles in maintaining systemic metabolic homeostasis,
      but our understanding of how the liver coordinates such a wide range of functions
      is still evolving. A recent study led by Dr. Gromada advanced the knowledge of
      the regulators for liver zonation with the discovery of a novel role for glucagon
      as a liver metabolic zonation regulator utilizing Glucagon (gcg) KO mice combined
      with RNA sequencing and in situ hybridization (ISH) (1). The established
      mechanism of metabolic liver zonation is determined by the architecture of the
      liver, which is composed of millions of hepatic lobules the basic functional
      units within each of the lobes of the liver. This article is protected by
      copyright. All rights reserved.

PMID- 30120895
TI  - Human cancer evolution in the context of a human immune system in mice.
AB  - Immunotherapy is one of the most promising cancer treatment modalities, but the
      lack of appropriate preclinical in vivo models hampers the development of novel
      immunotherapeutic strategies. Here, we studied the ability of transplanted human
      cancer cells to form primary tumors and metastasize in humanized immune system
      (HIS) mice created by transfer of CD34+ human hematopoietic stem cells. All
      tested transplanted cancer cell lines developed primary tumors that progressed
      nearly synchronously. Spontaneous lung and liver metastases developed from both
      orthotopic and ectopic transplanted cancer cells, and the ability to spread
      inversely correlated with the extent of CD8+ infiltration in the primary tumor.
      Further analysis revealed that interactions between the cancer model and the
      tumor-infiltrating lymphocytes created tumor microenvironments (TMEs) resembling
      clinical cancers. Some models were largely immune cell-excluding, while others
      appeared to develop adaptive resistance to immune-mediated destruction by
      increased expression of programmed death ligand 1 (PDL1) and recruitment of human
      regulatory T cells. Our data suggest that HIS mice may provide a promising in
      vivo tumor model for evaluating immune modulatory anticancer therapies. Moreover,
      our study identified different tumor models resembling specific types of human
      TMEs, rendering each beneficial for addressing disease-specific issues.

PMID- 30120898
TI  - Skin resident memory T-cell population is not constructed effectively in systemic
      sclerosis.

PMID- 30120900
TI  - Introduction to Guest Editorials.

PMID- 30120901
TI  - Psychosocial outcomes in cancer-bereaved children and adolescents: A systematic
      review.
AB  - OBJECTIVE: Due to the unique importance of parental and sibling relationships and
      concurrently existing developmental challenges, the loss of a parent or sibling
      due to cancer is a highly stressful event for children and adolescents. This is
      the first systematic review that integrates findings on psychosocial outcomes
      after parental or sibling cancer bereavement. METHODS: A systematic search of Web
      of Science, PubMed, PsycINFO, and PubPsych was conducted, last in December 2017.
      Quantitative studies on psychosocial outcomes of children and adolescents who
      lost a parent or sibling due to cancer were included. RESULTS: Twenty-four
      studies (N = 10 parental and N = 14 sibling bereavement), based on 13 projects,
      were included. Ten projects had cross-sectional designs. Only 2 projects used
      large, population-based samples and nonbereaved comparison groups. Outcomes were
      partially measured by single-item questions. Bereaved children and adolescents
      showed similar levels of depression and anxiety compared with nonbereaved or
      norms. Severe behavioral problems were found rarely. However, in 2 large,
      population-based studies, about half of the bereaved individuals reported
      unresolved grief. Bereaved adolescents had a higher risk for self-injury compared
      with the general population in one large, population-based study. Communication
      with health-care professionals, family, and other people; social support;
      distress during illness; age; gender; and time because loss were associated with
      psychosocial bereavement outcomes. CONCLUSIONS: Results indicate a high level of
      adjustment in cancer-bereaved children and adolescents. A modifiable risk factor
      for adverse psychosocial consequences is poor communication. Prospective designs,
      representative samples, and validated instruments, eg, for prolonged grief, are
      suggested for future research.

PMID- 30120899
TI  - Lathyrane-Type Diterpenoids from the Seeds of Euphorbia lathyris L. with
      Inhibitory Effects on NO Production in RAW 264.7 Cells.
AB  - Bioactivity-guided fractionation of the methanolic extract from the seeds of
      Euphorbia lathyris led to the isolation of 18 lathyrane-type diterpenoids
      including a new one, Euphorbia factor L29 (1). Their chemical structures were
      elucidated by extensive NMR spectroscopic data including 2D-NMR and HR-ESI-MS as
      well as CD data. All isolates (1 - 18) were found to inhibit the nitric oxide
      production in LPS-induced RAW 264.7 macrophages, with their IC50 values in the
      range of 11.2 - 52.2 MUm.

PMID- 30120903
TI  - Is Low Disease Activity Sufficient as a Target in Systemic Lupus Erythematosus?
      Comment on the Article by Petri et al.

PMID- 30120902
TI  - Cancer After Liver Transplantation in Children and Young Adults: A Population
      Based Study From 4 Nordic Countries.
AB  - Cancer after liver transplantation (LT) constitutes a threat also for young
      recipients, but cancer risk factors are usually absent in children and large
      studies on the cancer risk profile in young LT recipients are scarce. Data of
      patients younger than 30 years who underwent LT during the period 1982-2013 in
      the Nordic countries were linked with respective national cancer registries to
      calculate standardized incidence ratios (SIRs). A total of 37 cancer cases were
      observed in 923 patients with 7846 person-years of follow-up. The SIR for all
      cancer types, compared with the matched general population, was 9.8 (12.4 for
      males and 7.8 for females). Cumulative incidence of cancer adjusted for the
      competing risk of death was 2% at 10 years, 6% at 20 years, and 22% at 25 years
      after LT. Non-Hodgkin lymphoma was the most common cancer type (n = 14) followed
      by colorectal (n = 4) and hepatocellular cancer (n = 4). Age was a significant
      risk factor for cancer, and the absolute risk of most cancers (except for
      lymphoma) increased considerably in young adults older than 20 years. The cancer
      risk pattern is different in pediatric and young LT patients compared with adult
      recipients. The striking increase in cancer incidence in young adulthood after
      the second decade of life deserves further consideration in transition programs.

PMID- 30120904
TI  - Rv0474 is a copper-responsive transcriptional regulator that negatively regulates
      expression of RNA polymerase beta subunit in Mycobacterium tuberculosis.
AB  - We characterize Rv0474, a putative transcriptional regulatory protein of
      Mycobacterium tuberculosis, which is found to function as a copper-responsive
      transcriptional regulator at toxic levels of copper. It is an autorepressor, but
      at elevated levels (10-250 MUm) of copper ions the repression is relieved
      resulting in an increase in Rv0474 expression. Copper-bound Rv0474 is recruited
      to the rpoB promoter leading to its repression resulting in the growth arrest of
      the bacterium. Mutational analysis showed that the helix-turn-helix and leucine
      zipper domains of Rv0474 are essential for its binding to Rv0474 and rpoB
      promoters, respectively. The mechanism of Rv0474-mediated rpoB regulation seems
      to be operational only in pathogenic mycobacteria that can persist inside the
      host.

PMID- 30120905
TI  - Reply.

PMID- 30120906
TI  - Are radio-contrast agents commonly used in discography toxic to the intact
      intervertebral disc tissue cells?
AB  - In the literature, there have been no studies showing clear results on how radio
      contrast pharmaceuticals would affect intact disc tissue cells. In this context,
      it was aimed to evaluate the effects of iopromide and gadoxetic acid, frequently
      used in the discography, on intact lumbar disc tissue in pharmaco-molecular and
      histopathological level. Primary cell cultures were prepared from the healthy
      disc tissue of the patients operated in the neurosurgery clinic. Except for the
      control group, the cultures were incubated with the indicated radio-contrast
      agents. Cell viability, toxicity and proliferation indices were tested at
      specific time intervals. The cell viability was quantitatively analysed. It was
      also visually rechecked under a fluorescence microscope with acridine
      orange/propidium iodide staining. Simultaneously, cell surface morphology was
      analysed with an inverted light microscope, while haematoxylin and eosin (H&E)
      staining methodology was used in the histopathological evaluations. The obtained
      data were evaluated statistically. Unlike the literature, iopromide or gadoxetic
      acid did not have any adverse effects on the cell viability, proliferation and
      toxicity (P < 0.05). Although this study reveals that radio-contrast
      pharmaceuticals used in the discography, often used in neurosurgical practice,
      can be safely used, it should be remembered that this study was performed in an
      in vitro environment.

PMID- 30120907
TI  - Secretory tumors of the pituitary gland: a clinical biochemistry perspective.

PMID- 30120908
TI  - Standardization and harmonization of autoimmune diagnostics.

PMID- 30120909
TI  - The choice of progestogen for HRT in menopausal women: breast cancer risk is a
      major issue.

PMID- 30120910
TI  - Re-establishing normal diet following high fat-diet-induced obesity reverses the
      altered salivary composition in Wistar rats.

PMID- 30120911
TI  - Integrative Bioinformatics Analysis Reveals Potential Long Non-Coding RNA
      Biomarkers and Analysis of Function in Non-Smoking Females with Lung Cancer.
AB  - BACKGROUND Lung cancer is the most lethal cancer worldwide. The aim of this study
      was to identify the tumor-related lncRNAs and explore their functions in female
      non-smokers with lung cancer. MATERIAL AND METHODS The gene expression microarray
      datasets GSE19804, GSE31210, and GSE31548 were downloaded from the Gene
      Expression Omnibus database. The differentially-expressed lncRNAs between non
      smoking female lung cancer samples and non-tumor lung tissues were identified
      using GEO2R. RESULTS In total, 25, 40, and 15 differentially-expressed lncRNAs
      were obtained from GSE19804, GSE31210, and GSE31548 datasets (|logFC| >1, adj.
      P<0.05), respectively. Eight lncRNAs were screened out in all 3 datasets. Of
      these, 5 lncRNAs were up-regulated and 3 lncRNAs were down-regulated in lung
      cancer tissues compared to non-tumor lung tissues. Then, the target miRNAs of
      aberrantly expressed lncRNAs and target mRNAs corresponding to miRNAs were
      predicted. Subsequently, the ceRNA network with 8 key lncRNAs, 20 miRNAs, and 38
      mRNAs were constructed. Functional and pathway enrichment analysis showed these
      target genes were mainly enriched in biological processes associated with protein
      binding, nucleus, metal ion binding, regulation of transcription from RNA
      polymerase II promoter, nucleic acid binding, cell differentiation, microRNAs in
      cancer, and the hippo signaling pathway. Survival analysis of these lncRNAs
      revealed that low LINC00968 (P=0.0067) and TBX5-AS1 (P=0.0028) expression were
      associated with unfavorable prognosis in never-smoking female lung cancer
      patients. CONCLUSIONS The present study promotes understanding of the molecular
      mechanism of the pathogenesis of non-smoking female lung cancer and provides
      potential biomarkers for diagnosis and treatment.

PMID- 30120912
TI  - Targeted sequencing and intracranial outcomes of patients with lung
      adenocarcinoma brain metastases treated with radiotherapy.
AB  - BACKGROUND: Treatment for advanced lung adenocarcinoma (AC) has become
      increasingly personalized based on molecular results. However, for patients with
      AC brain metastases (BMs), intracranial outcomes based on molecular subtype and
      the frequency of molecular aberrations are less well defined. This study sought
      to report targeted next-generation sequencing results and investigate molecularly
      based outcomes for patients with AC-BMs treated with radiotherapy. METHODS: The
      records of 132 patients with AC-BMs treated at Emory University from September
      2008 to August 2016 with successful next-generation sequencing were reviewed.
      Rates of local disease recurrence, distant brain failure (DBF), and salvage whole
      brain radiotherapy (WBRT) were estimated using cumulative incidence with
      competing risk analysis. Univariate and multivariate analyses were performed.
      RESULTS: The most common aberrations included tumor protein 53 (TP53) (60%), KRAS
      (29%), epidermal growth factor receptor (EGFR) (20.5%), phosphatase and tensin
      homolog (PTEN) loss (15.5%), and MET amplification (13%). The majority of
      patients (62%) were treated with stereotactic radiosurgery alone. In these
      patients, KRAS mutation, anaplastic lymphoma kinase (ALK) rearrangement, and
      having >= 6 BMs were associated with an increased risk of salvage WBRT (P < .05).
      KRAS mutation remained significant for an increased risk of salvage WBRT when
      compared with EGFR/ALK/KRAS-negative patients (hazard ratio, 5.17; P < .05),
      despite a similar risk of DBF. PTEN loss was associated with increased risk of
      DBF (P < .05), whereas EGFR and ALK aberrations were associated with a decreased
      risk of local disease recurrence (P < .05). CONCLUSIONS: The results of the
      current study quantified the frequency of genetic aberrations in patients with AC
      BMs and demonstrated their association with intracranial outcomes. In particular,
      a cohort of patients with KRAS mutations and >=6 BMs were identified to be at
      high risk of requiring salvage WBRT after undergoing upfront stereotactic
      radiosurgery.

PMID- 30120913
TI  - Autoantibody to transcriptional intermediary factor-1beta as a myositis-specific
      antibody: clinical correlation with clinically amyopathic dermatomyositis or
      dermatomyositis with mild myopathy.
AB  - BACKGROUND: Myositis-specific autoantibodies (MSAs) are associated with unique
      clinical subsets in polymyositis/dermatomyositis (PM/DM). Autoantibodies against
      transcriptional intermediary factor (TIF)-1gamma and TIF-1alpha are known to be
      MSAs. Previously, we reported that TIF-1beta is also targeted in patients with DM
      with or without concomitant anti-TIF-1alpha/gamma antibodies. OBJECTIVES: To
      evaluate the clinical features of seven cases with anti-TIF-1beta antibodies
      alone. METHODS: Serum autoantibody profiles were determined, and protein and RNA
      immunoprecipitation studies were conducted. Western blotting was performed to
      confirm autoantibody reactivity against TIF-1beta. RESULTS: Anti-TIF-1beta
      antibody was identified by immunoprecipitation assay in 24 cases. Among them,
      seven patients were positive for anti-TIF-1beta antibody alone. Six of the seven
      patients were classified as having DM. Among the six cases of DM, two patients
      had no muscle weakness and normal creatine kinase (CK) levels, and were
      classified as having clinically amyopathic DM. Four patients had muscle weakness,
      but three of them had normal serum CK levels that responded well to systemic
      steroids. Characteristic features of DM included skin rashes, such as Gottron
      sign, periungual erythema, punctate haemorrhage on the perionychium and facial
      erythema including heliotrope, which were observed in 86%, 57%, 86% and 71% of
      our cases, respectively. One of the seven patients had appendiceal cancer. None
      of the patients had interstitial lung disease. CONCLUSIONS: Seven patients were
      confirmed to have anti-TIF-1beta antibody without any other MSAs, including TIF
      1alpha/gamma antibodies, and six of them were diagnosed with DM. We suggest that
      anti-TIF-1beta antibody is an MSA, and that it is associated with clinically
      amyopathic DM or DM with mild myopathy.

PMID- 30120914
TI  - [Identification and Expression of the yellow Gene Family in Aedes aegypti].
AB  - Objective: To identify the yellow family genes in Aedes aegypti and analyze the
      gene structure, phylogenetic evolution and their expression at various
      developmental stages and in different tissues. Methods: The yellow gene family
      was identified in Ae. aegypti by blasting the Ae. aegypti genome database with
      the amino acid sequence of the MRJP domain of Dm-yellow gene of Drosophila
      melanogaster(GenBank No. AAF45497). The physico-chemical property and domains
      were analyzed with the on-line ExPaSy software. The signal peptide was predicted
      using SignalP4.1 software. Sequence alignment and the phylogenetic tree were made
      through combined use of DNAstar, MEGA6.0 and GeneDoc. Total RNA was extracted
      from Ae. aegypti, cDNA was generated, and expression of the yellow family genes
      at various developmental stages (egg, first to fourth instar, pupa, non-blood-fed
      female and male mosquitoes) and in different tissues (salivary gland, midgut, fat
      body, and ovary) was quantified using qRT-PCR. Results: Twelve yellow genes were
      identified from Ae. aegypti genome: Aa-yellow, Aa-yellow-b, Aa-yellow-c, Aa
      yellow-d, Aa-yellow-e, Aa-yellow-f2, Aa-yellow-fb, Aa-yellow-fc, Aa-yellow-g, Aa
      yellow-g2, Aa-yellow-h, and Aa-yellow-x. Bioinformatics demonstrated that all
      covered the MRJP domain and a signal peptide sequence. Sequence alignment
      revealed low (15%-49%) homology among the proteins, but high homology(60%) in the
      conserved domain. According to the phylogenetic tree analysis, the encoded 12
      YELLOW proteins were classified into 5 subfamilies, and 11 had orthologues in D.
      melanogaster. qRT-PCR revealed high expression of Aa-yellow-d (0.018 9) and Aa
      yellow-x (0.023 5) in male Ae. aegypti (P<0.01 or P<0.05); high expression of Aa
      yellow-fc (0.024 8, 0.034 9) in female Ae. aegypti and in the salivary gland
      (P<0.01); high expression of Aa-yellow-f2 (0.093 4) in the second instar stage
      (P<0.01); high expression of Aa-yellow (0.562 1), Aa-yellow-e (0.004 4), and Aa
      yellow-fb (0.008 4) in the third instar stage (P<0.05); and high expression of Aa
      yellow (0.569 4), Aa-yellow-e (0.027 0), Aa-yellow-f2 (0.006 5), Aa-yellow-fb
      (0.001 0), Aa-yellow-h (0.084 8) and Aa-yellow-x (0.015 1) in the ovary. Genes
      other than Aa-yellow-c (0.004 0) and Aa-yellow-x (0.007 4) were hardly expressed
      in the midgut. Conclusion: The 12 yellow genes identified in the Ae. aegypti
      genome have low homology, and are differentially expressed at different
      developmental stages and in tissues.

PMID- 30120915
TI  - [Helminth Infections in Goats in Nimu County of Tibet].
AB  - Postmortem examinations were made in 99 goats in Nimu County of Tibe, and
      parasites were collected and identified based on morphology. The collected
      parasites were categorized, and infection status was analyzed. The helminth
      infection rate was 100% among the goats, and all showed a pattern of mixed
      infection. The identified parasites belonged to 21 species, 15 genera, and 9
      families. The Trichuris genus(36.4%) was the most prevailing among nematodes in
      the gastrointestinal tract; Paramphistomum cervi(60.6%) and Paramphistomum
      gotoi(60.6%) were predominant among trematodes detected; Cysticercus
      tenuicollis(52.5%) was the predominant cestode detected; and Orientobilharzia
      turkestanicum was the major parasite detected in the portal vein (69.7%).

PMID- 30120917
TI  - [ Epidemiological Analysis of Imported Malaria in Shijiazhuang City from 2010 ].
AB  - Epidemiological analysis was performed on the 103 reported malaria cases during
      2010-2014 in Shijiazhuang City. All the cases were imported from abroad,
      comprising 18(17.5%) cases of vivax malaria, 43 (41.7%) falciparum malaria,
      2(1.9%) ovale malaria, 18(17.5%) cases with mixed infections, and 22(21.4%)
      unclassified cases. No significant seasonal variation in disease onset was
      observed. The male-to-female ratio was 33.3 : 1 and the cases were concentrated
      within 20-50 years. Africa was the main source of imported cases (92.2%).

PMID- 30120916
TI  - [Medical Costs on Malaria in Henan Province and Analysis of the Influential
      Factors].
AB  - Objective: To analyze the costs for the diagnosis and treatment of malaria in
      Henan Province and the influential factors. Methods: Malaria cases diagnosed in
      and reported by medical institutions in Henan Province from November 2013 to
      October 2014 were selected. General information and clinical information of those
      with further microscopic confirmation were also collected. The rank sum test for
      two or more independent samples and stepwise regression analysis were used to
      investigate the influential factors for medical costs. Results: A total of 218
      malaria cases were finally included, of whom 73.4% were from rural areas. On
      average, the medical costs for patients from rural areas and cities/towns were 1
      503 yuan and 4 833 yuan respectively. The average medical cost per patient with
      first-visit in rural hospitals was 2 600 yuan, and that with first-visit in
      provincial hospitals was 7 800 yuan. The average medical costs for patients
      diagnosed in county/city-level hospitals and provincial hospitals were 1 022.5
      yuan and 6 170 yuan, respectively. There was null cost for patients diagnosed at
      the first-visit, while for those diagnosed after 3 or more visits the average
      cost per patient was 5 621 yuan. Factors significantly associated with medical
      costs were the current living locality of patients, the hospital level of first
      visit, the hospital level of diagnosis and the number of visits before
      diagnosis(P<0.05). Stepwise regression analysis showed that the hospital level of
      first-visit was the most important influential factor for medical cost, followed
      by the hospital level of diagnosis and the number of visits before diagnosis. The
      higher hospital levels of first-visit and diagnosis, the higher cost. The same
      applied to the number of visits before diagnosis. Conclusion: There is an
      considerable correlation between medical cost and health seeking behavior in
      malaria patients.

PMID- 30120918
TI  - [Effect of Echinococcus multilocularis Infection on the Activities of Drug
      metabolizing Enzymes in Gerbil Liver].
AB  - Objective: To study the effect of Echinococcus multilocularis infection on the
      activities of drug-metabolizing enzymes in gerbil liver. Methods: Ten gerbils
      (Meriones unguiculatus) were randomly divided into 2 groups, the experimental
      group in which each animal was intraperitoneally injected with 300 MUl E.
      multilocularis cyst homogenates (containing about 600 protoscoleces), and the
      control group in which each animal received 300 MUl saline(i.p.). Five months
      after infection, the animals were sacrificed by cervical dislocation, and livers
      were collected. The liver microsomal and cytosolic fractions were obtained by
      differential centrifugation. Protein concentration was measured by the BCA
      method. CYP450 and Cyt b5 contents in the microsomal fraction were measured with
      differential spectroscopy. Activities of 7-ethoxyresorufin(EROD) and 7
      methoxyresorufin(MROD) were measured by fluorescence spectrometry. The activities
      of NADPH-cytochrome C reductase(NCR), glutathione-S-transferase (GST), and
      flavine monooxygenases (FMO) were measured by UV-visible spectrophotometry.
      Results: The protein content of cytosolic fractions and liver microsomes in
      experimental group was (11.089+/-1.277) and (3.212+/-0.924) mg/ml, those in
      control group was (12.459+/-1.625) and (3.894+/-0.395) mg/ml, respectively. The
      contents of CYP450 and Cyt b5 in the experimental group [(0.508+/-0.142),
      (0.515+/-0.077) nmol/mg protein, respectively] were both significantly lower than
      those in the control [(0.647+/-0.090), (0.596+/-0.051) nmol/mg protein](P<0.05).
      The GST activity decreased significantly in the experimental group [(1.766+/
      0.339)*103 nmol/(mg.min)] compared with the control [(2.001+/-0.160)*103
      nmol/(mg.min)](P<0.05). But the FMO and NCR activities increased significantly in
      the experimental group [(1.142+/-0.327) nmol/(mg.min) and (0.602+/-0.162)*103
      nmol/(mg.min), respectively] compared with the control [(0.882+/-0.150)
      nmol/(mg.min) and (0.442+/-0.082)*103 nmol/(mg.min)](P<0.05). However, there were
      no significant differences in EROD and MROD activities between the two groups
      (P>0.05). Conclusion: The activities of FMO and NCR markedly increase, while that
      of GST significantly decreases in the gerbil liver after E. multilocularis
      infection.

PMID- 30120919
TI  - [Cloning and Expression of Tibetan Sheep-origin Echinococcus granulosus Antigen B
      Gene and Protein Identification Using Immunological Method].
AB  - Objective: To clone and express the Tibetan Sheep-origin Echinococcus granulosus
      Antigen B8/2 Gene, and immunologically identify the encoded protein. Methods: The
      cDNA of EgAgB8/2 gene was amplified by RT-PCR. The prokaryotic expression vector
      pET-EgAgB8/2 was constructed and transformed into E. coli BL21(DE3) for
      expression. Proteins were extracted, separated in SDS-PAGE and identified by
      Western blotting. Results: The cloned EgAgB8/2 gene was 335 bp in length, and had
      a 98%-100% sequence homology with the reported cDNA sequence of EgAgB8/2,
      indicating the successful construction of the pET-EgAgB8/2 vector. SDS-PAGE
      revealed large amount of proteins in supernatant. Western blotting further
      confirmed the expression of the target protein. Conclusion: The EgAgB8/2 gene of
      Tibetan Sheep-origin in Qinghai is successfully cloned, and the constructed pET
      EgAgB8/2 vector can be used to express the target protein.

PMID- 30120921
TI  - The release of glycosylphosphatidylinositol-anchored proteins from the cell
      surface.
AB  - Starting with the first description of the anchorage of a subset of cell surface
      proteins in eukaryotic cells from yeast to mammals with the aid of a
      glycosylphosphatidylinositol (GPI) moiety covalently attached to the carboxy
      terminus of the protein, experimental evidence for the potential of GPI-anchored
      proteins (GPI-AP) of being released into the extracellular environment has been
      accumulating. GPI-AP are released as soluble monomers or multimers having lost
      their anchor or within hetero-/multimeric assemblies with their complete anchor
      remaining attached. The configurations reported so far for those assemblies
      encompass carrier protein-bound monomers, phospholipid- and cholesterol-harboring
      micelle-like complexes as well as membrane vesicles and particles. Each of these
      configurations prevents direct contact of the GPI anchor with the aqueous
      environment. Their structural diversity is reflected in the different molecular
      mechanisms underlying their release, which involve (i) proteolytic or lipolytic
      cleavage of the protein or GPI moiety, respectively, (ii) masking of the GPI
      anchor in the binding pocket of carrier proteins or in the phospholipid mono- or
      bilayers of particles or vesicles, respectively, and (iii) direct transfer of
      anchor-harboring GPI-AP from donor to acceptor cells through intimate contact of
      their plasma membranes. Release of GPI-AP may occur spontaneously or in response
      to certain endogenous or environmental stress signals and exert specific roles in
      the (patho)physiology of eukaryotic organisms which, however, are only
      incompletely understood so far.

PMID- 30120920
TI  - [Expression and Activity of Arginase from Monocytic-type Myeloid-derived
      Suppressor Cells in Rats Infected with Echinococcus granulosus].
AB  - Objective: To investigate the alteration of expression and activity of arginase
      from monocytic-type myeloid-derived suppressor cells(M-MDSC) in BALB/c mice
      infected with Echinococcus granulosus. Methods: Twelve BALB/c female mice were
      randomly divided into control and infected groups. The mice were injected
      intraperitoneally with 2 000 live protoscoleces or an equivalent volume of normal
      saline. After 120 days, peripheral blood was collected through venae orbitaeta,
      and mice were sacrificed for pathological examination. The spleen was collected
      under aseptic conditions and single-cell suspension was prepared for M-MDSC
      isolation using the magnetic bead separation technology. Total RNA was extracted
      from M-MDSC, cDNA was generated, and genes with differential expression without
      and with infection were screened using the chip hybridization method. The
      resulting genes were further validated using real-time PCR. The activity of
      arginase from peripheral blood was also measured. Results: Single cyst was formed
      within the abdomen and internal organs 120 days after infection. Chip
      hybridization and real-time PCR showed that the relative expression of arginase
      from M-MDSC in the infected group (7.92+/-0.85 and 11.97+/-5.39, respectively)
      was significantly higher than that in the control group (1.65+/-0.19 and 1.00+/
      0.57, respectively) (P<0.05). The activity of arginase was also significantly
      higher in the infected group [(3.83+/-0.44)U/L] than in the control [(1.57+/
      0.57)U/L]. Conclusion: The expression and activity of arginase from mouse M-MDSC
      both increase significantly after infection with Echinococcus granulosus.

PMID- 30120922
TI  - Induction of beige adipocytes by naturally occurring beta3-adrenoceptor agonist p
      synephrine.
AB  - The prevalence of obesity and its associated diseases is increasing worldwide,
      and the therapeutic potential of increasing energy expenditure through
      differentiation or activation of beige adipocytes has attracted much interest.
      Therefore, we explored naturally occurring compounds that induce beige adipocytes
      by screening for activity to induce mRNA expression of uncoupling protein 1
      (UCP1) in stromal vascular fraction (SVF) cells cultured in beige adipocyte
      differentiation medium. Through screening, p-synephrine, a compound isolated from
      Citrus unshiu Marcov., was found to be an active compound that increased UCP1
      mRNA expression in a dose-dependent manner from a concentration of 3.12 uM, which
      induced morphological changes specific for beige adipocytes. Similar effects were
      also observed in SVF cells prepared from db/db obese mice. While investigating
      the underlying mechanism of p-synephrine-induced beige adipocyte differentiation,
      we found that the effects of p-synephrine were abolished by the beta3
      adrenoceptor antagonist SR58894. Intriguingly, p-synephrine increased UCP1 mRNA
      levels in SVF cells cultured in beige adipocyte differentiation medium lacking
      insulin to an extent different from those by the beta-agonist isoprenaline.
      Furthermore, phosphatidylinositol 3-kinase inhibitor LY294002 decreased
      isoprenaline-induced UCP1 mRNA levels in the early phase of beige adipocyte
      differentiation and p-synephrine-induced UCP1 mRNA levels in fully differentiated
      beige adipocytes. Thus, p-synephrine appears to elicit signals via beta3
      adrenoceptor combined with some part of the insulin signaling pathway, finally
      resulting in efficient stimulation of beige adipocyte differentiation with the
      support of certain beige adipocyte differentiation-inducing factors. The present
      results suggest the potential of p-synephrine for prophylaxis and treatment of
      obesity and its associated diseases.

PMID- 30120923
TI  - Selenothymidine protects against biochemical and behavioral alterations induced
      by ICV-STZ model of dementia in mice.
AB  - The present study evaluated the neuroprotective effects of one selenium
      containing AZT derivative compound (S1073) in memory and learning impairment
      caused by Intracerebroventricular-streptozotocin (ICV-STZ). ICV-STZ in mice
      causes impairment of energy metabolism with oxidative damage and cholinergic
      dysfunction, and provides a relevant model for sporadic dementia of Alzheimer's
      type (AD). Acetylcolinesterase (AChE), Catalase (CAT), dichlorofluorescein
      oxidation (DCFH), TBARS and thiol content were measured. Swiss adult mice were
      pre-treated with S1073 [1 mmol/kg] (i.p.) and after 30 min of the injection
      received a bilateral dose of STZ [11.3 MUmol/l]. After 8 days' STZ injection, we
      performed the behavioral experiments (Beaker test, Open field and Morris water
      maze task). ICV-STZ caused significant learning and memory impairments, which
      were significantly improved by S1073 pre-treatment. A significant increase in
      cerebral DFCH, TBARS levels and AChE activity and a disturbance in the memory and
      learning were observed in ICV-STZ injected animals. S1073 significantly
      ameliorated all alterations induced by ICV-STZ in mice. All these findings
      support the neuroprotective role of S1073 in mice model of Alzheimer's dementia
      type induced by ICV-STZ, which may be associated with its antioxidant activity
      and/or with its inhibitory effect in brain AChE. In fact, in silico analysis
      indicated that S1073 may be an inhibitor of AChE.

PMID- 30120924
TI  - Fluorescent copper nanoclusters as a nano-dye for DNA methyltransferase activity
      analysis and inhibitor screening.
AB  - Fluorescent copper nanoslusters (CuNCs) as a new class of fluorophores have
      attracted more and more attention due to their ease of synthesis, excellent
      optical properties, and low cost. In this study, a novel label-free fluorescent
      method was developed for the detection of DNA methyltransferases based on
      template length-dependent of dsDNA-CuNCs. In the absence of DNA adenine
      methylation methyltransferase (Dam MTase), the dsDNA containing the methylation
      responsive sequence could effectively template the formation of fluorescent CuNCs
      with bright fluorescence. When the dsDNA substrate is methylated by Dam MTase,
      the methylation-sensitive restriction endonuclease Dpn I cleaves the methylated
      dsDNA and produces shorter dsDNA product, which fails to template fluorescent
      CuNCs. So, the Dam MTase activity could be identified by the changes of CuNCs'
      fluorescence. Based on this method, a linear range of 0.5-10 U/mL was achieved
      with high sensitivity and selectivity. Moreover, we also demonstrate the proposed
      method can be applied to evaluation and screening of inhibitors for Dam MTase.

PMID- 30120925
TI  - An observational study to test the acceptability and feasibility of using medical
      and nursing students to instruct clients in DMPA-SC self-injection at the
      community level in Kinshasa.
AB  - OBJECTIVES: Given the promise of DMPA-SC to increase community-level access to
      modern contraception in developing countries, we conducted an observational study
      to assess the acceptability and feasibility of DMPA-SC self-injection among women
      in Kinshasa, Democratic Republic of the Congo, and of medical/nursing (M/N)
      students as instructors for self-injection. STUDY DESIGN: Women who selected DMPA
      SC at a community outreach event adjacent to a health center were interviewed
      upon acceptance (baseline) and then 3, 6 and 12 months later. RESULTS: Of 850
      clients selecting DMPA-SC at baseline, 640 (75.3%) opted for self-injection over
      being injected by the M/N students for reasons of convenience and personal
      agency. Among these 640 self-injectors, 47.5% were anxious at baseline (for fear
      of needles or injecting incorrectly). Over 80% reported feeling very ready after
      training, confident that they knew how to self-inject and confident that they
      would remember the next injection date. By 3 months, 97% described it as easy.
      Half (54%) experienced side effects, mainly menstrual irregularities, the main
      reason for discontinuation. At 6-month follow-up, self-injectors cited
      effectiveness and ease of use as positive elements, though one quarter reported
      side effects. Their impressions of M/N students as instructors were highly
      positive. CONCLUSIONS: Where DMPA-SC was free and easily accessible, the majority
      of women interested in DMPA-SC opted to learn self-injection. The M/N students
      performed well in instructing women to self-inject. Clients were highly satisfied
      with the services received, yet many did not recognize their student status,
      possibly because outreach occurred near a health facility. Once told, clients
      remained very favorable, suggesting strong motivation to receive their preferred
      contraceptive free, whoever the provider. IMPLICATION STATEMENT: This study
      provides additional evidence on the acceptability and the feasibility of the self
      injection of DMPA-SC by users from a resource-limited setting.

PMID- 30120926
TI  - Planned, unplanned and in-between: the meaning and context of pregnancy planning
      for young people.
AB  - OBJECTIVE: To understand how young people conceptualize planned, unplanned and
      "in-between" pregnancies. METHODS: We conducted individual qualitative interviews
      with 50 young (ages 18-24) women and their male partners (n=100) in the San
      Francisco Bay Area to investigate prospective pregnancy intentions. In this
      analysis, we focused on participants' conceptualization of planned and unplanned
      pregnancies, as well as a status in between planned and unplanned. RESULTS:
      Conceptualizations of pregnancy planning were influenced by personal experiences
      and life circumstances, including previous unplanned pregnancies. While many
      participants held up planned pregnancies as an ideal, the majority of
      participants (n=71) also felt that a status in between planned and unplanned
      pregnancy existed. Many described this in-between stage occurring when someone is
      "not not trying" or would find an unplanned pregnancy acceptable. Notably, a few
      participants mentioned that pregnancy planning was not possible because either it
      was uncommon among their peers or they felt a general lack of control over
      pregnancy. CONCLUSION: Our analysis suggests that binary operationalization of
      pregnancies as "planned" and "unplanned" neglects the complexity of young
      people's lived experiences and perspectives. Contraceptive counseling approaches
      that allow patients the flexibility to express their considerations and feelings
      toward a potential future pregnancy could improve the quality of family planning
      visits and patient-provider interactions. IMPLICATIONS: The traditional binary
      conceptualization of pregnancies as planned and unplanned may not holistically
      capture the diverse perspectives of young people. Increased understanding of the
      complexities in young people's conceptualizion of pregnancy planning can inform
      family planning care that is inclusive, relevant and supportive of a variety of
      perspectives.

PMID- 30120928
TI  - Correlation of spectral domain optical coherence tomography with histology and
      electron microscopy in the porcine retina.
AB  - Spectral domain optical coherence tomography (SD-OCT) is used as a non-invasive
      tool for retinal morphological assessment in vivo. Information on the correlation
      of SD-OCT with retinal histology in the porcine retina, a model resembling the
      human retina, is limited. Herein, we correlated the hypo- and hyper-reflective
      bands on SD-OCT with histology of the lamellar architecture and cellular
      constituents of the porcine retina. SD-OCT images were acquired with the
      Heidelberg Spectralis HRA + OCT. Histological analysis was performed using epoxy
      resin embedded tissue and transmission electron microscopy. Photomicrographs from
      the histologic sections were linearly scaled to correct for tissue shrinkage and
      correlated with SD-OCT images. SD-OCT images correlated well with
      histomorphometric data. A hyper-reflective band in the mid-to-outer inner nuclear
      layer correlated with the presence of abundant mitochondria in horizontal cell
      processes and adjacent bipolar cells. A concentration of cone nuclei corresponded
      to a relative hypo-reflective band in the outer portion of the outer nuclear
      layer. The presence of 3 hyper-reflective bands in the outer retina corresponded
      to: 1) the external limiting membrane; 2) the cone and rod ellipsoid zones; and
      3) the interdigitation zone of photoreceptor outer segments/retinal pigment
      epithelium (RPE) apical cell processes and the RPE. These correlative and
      normative SD-OCT data may be employed to characterize and assess the in vivo
      histologic changes in retinal vascular and degenerative diseases and the
      responses to novel therapeutic interventions in this large animal model.

PMID- 30120929
TI  - Modulation of xenobiotic nuclear receptors in high-fat diet induced non-alcoholic
      fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver
      disease in the western countries. The histological spectrum of NAFLD includes
      simple steatosis, steatohepatitis, fibrosis, cirrhosis and even hepatocellular
      carcinoma. Nuclear receptors are a large group of ligand-dependent transcription
      factors that sense the environmental and endogenous changes and regulate numerous
      physiological and pathological processes. Accumulating evidence has suggested
      that a dysregulation of nuclear receptors in NAFLD may effect on the metabolism
      of endogenous and exogenous chemicals in the liver. The current study was
      designed to systematically characterize the time-dependent modulation of nuclear
      receptors including the peroxisome proliferator-activated receptors (PPARs), the
      constitutive androstane receptor (CAR), the pregnane X receptor (PXR), the liver
      X receptor (LXR), and the farnesoid X receptor (FXR) in the progression of NAFLD.
      Male C57BL/6 mice fed by a high fat diet were used to induce NAFLD. Hepatic
      steatosis, lobular inflammation, progressive fibrosis, increased hepatocyte DNA
      synthesis, and liver tumor formation were observed at various time points in our
      mouse model. During the development of hepatic steatosis (8-16 weeks), PPARalpha
      was activated as indicated by its target genes as well as the elevated
      peroxisomal acyl-CoA oxidase activity. The mRNA level of Ppargamma was also
      upregulated while Ppardelta gene expression was significantly reduced during the
      development of hepatic steatosis. PXR target gene Cyp3a11 was consistently
      increased 3-4-fold in addition to the increased microsomal Cyp3a enzymatic
      activity at all stages of NAFLD. In contrast, CAR mediated Cyp2b10 gene
      expression was found increased only by week 12. LXRalpha target genes Abcg5 and
      Abcg8 were significantly elevated during the whole course of NAFLD. The mRNA of
      Fxr was downregulated at 24 and 32 weeks in high fat diet fed mice, which might
      correlate with the development of progressive fibrosis at the stage of
      steatohepatitis. The results of our study provided a systematic evaluation of the
      changes of nuclear receptors and their downstream chemicalmetabolism and
      transport enzymes in the progression of NAFLD.

PMID- 30120927
TI  - CBD-1 organizes two independent complexes required for eggshell vitelline layer
      formation and egg activation in C. elegans.
AB  - Metazoan eggs have a specialized coat of extracellular matrix that aids in sperm
      egg recognition. The coat is rapidly remodeled after fertilization to prevent
      polyspermy and establish a more permanent barrier to protect the developing
      embryo. In nematodes, this coat is called the vitelline layer, which is remodeled
      into the outermost layer of a rigid and impermeable eggshell. We have identified
      three key components of the vitelline layer structural scaffold - PERM-2, PERM-4
      and CBD-1, the first such proteins to be described in the nematode C. elegans.
      CBD-1 tethered PERM-2 and PERM-4 to the nascent vitelline layer via two N
      terminal chitin-binding domains. After fertilization, all three proteins
      redistributed from the zygote surface to the outer eggshell. Depletion of PERM-2
      and PERM-4 from the scaffold led to a porous vitelline layer that permitted
      soluble factors to leak through the eggshell and resulted in embryonic death. In
      addition to its role in vitelline layer assembly, CBD-1 is also known to anchor a
      protein complex required for fertilization and egg activation (EGG-1-5/CHS-1/MBK
      2). We found the PERM complex and EGG complex to be functionally independent, and
      structurally organized through distinct domains of CBD-1. CBD-1 is thus a
      multifaceted regulator that promotes distinct aspects of vitelline layer assembly
      and egg activation. In sum, our findings characterize the first vitelline layer
      components in nematodes, and provide a foundation through which to explore both
      conserved and species-specific strategies used by animals to build protective
      barriers following fertilization.

PMID- 30120930
TI  - Excitotoxic lesion of the medial prefrontal cortex in Wistar rats: Effects on
      trait and state anxiety.
AB  - The neural substrate of anxiety response (state anxiety) to a threatening
      situation is well defined. However, a lot less is known about brain structures
      implicated in the individual's predisposition to anxiety (trait anxiety).
      Scientific evidences lead us to suppose that the medial prefrontal cortex (mPFC)
      is involved in both trait and state anxiety. Thus, the aim of this study was to
      investigate the involvement of mPFC in trait anxiety and to further evaluate its
      participation in state anxiety. Sixty six adult, Wistar, male rats were first
      tested in the free-exploratory paradigm (FEP) and were categorized according to
      their levels of trait anxiety (high, medium and low). Three to six days after
      this exposure, all animals were submitted to stereotaxic brain surgery. Half the
      animals from each anxiety category was allocated to the mPFC-lesioned group and
      the other half to the Sham-lesioned group. After seven to nine days, all animals
      were again tested in FEP. Eight to 10 days later, the animals were tested in the
      Hole Board test, a model of state anxiety. The mPFC lesion decreased levels of
      trait anxiety of highly anxious rats, whereas it reduced the state anxiety of all
      animals, regardless the level of trait anxiety. These data extend evidence of the
      participation of the mPFC in state anxiety and it demonstrate the involvement of
      this brain structure in trait anxiety, a personality trait supposed to be a
      predisposing factor for anxiety disorders.

PMID- 30120931
TI  - Kinetic time courses of lambda-cyhalothrin metabolites after dermal application
      of Matador EC 120 in volunteers.
AB  - A controlled kinetic study was conducted in volunteers dermally exposed to the
      widely used lambda-cyhalothrin pyrethroid pesticide to document the time courses
      of relevant biomarkers of exposure, in order to better assess biomonitoring data
      in workers. Matador(r) EC120 formulation (120 g/l) was applied on 40 cm2 of the
      forearm at a 0.25 mg/kg dose of lambda-cyhalothrin and left without occlusion or
      washing for 6 h. The application site was then washed thoroughly with soap and
      water. The kinetic time courses of cis-3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)
      2,2-dimethylcyclopropane carboxylic acid (CFMP) and 3-phenoxybenzoic acid (3-PBA)
      metabolites were determined in plasma and urine up to 84 h post-application.
      Results show that the fraction of lambda-cyhalothrin absorbed in the body was
      rapidly cleared following dermal contact. According to CFMP and 3-PBA plasma
      profiles, calculated mean apparent absorption half-lives (t1/2) were 3 and 7.3 h,
      respectively, and corresponding mean apparent elimination t1/2 were 11.2 and 7.6
      h. These differences suggest some metabolism at the site-of-entry and storage of
      metabolites by the dermal route. Toxicokinetic parameters calculated from urinary
      profiles confirm the values of absorption and elimination rates. Metabolites were
      almost completely excreted over the 84-h period post-application and, on average,
      0.12 and 0.08% of the applied lambda-cyhalothrin dose was recovered in the urine
      as CFMP and 3-PBA, respectively, indicating a low dermal absorption fraction of
      this pyrethroid. This study showed the potential use of CFMP and 3-PBA biomarkers
      for the assessment of dermal exposure to lambda-cyhalothrin pyrethroid.